PMID- 24011863
TI  - In pre-school children, sleep objectively assessed via sleep-EEGs remains stable
      over 12 months and is related to psychological functioning, but not to cortisol
      secretion.
AB  - STUDY OBJECTIVES: Cross-sectional studies provide evidence that in pre-schoolers
      poor sleep is by this age already associated with both poor psychological
      functioning and an increased cortisol secretion. However, long-term studies on
      the stability of sleep in pre-schoolers are scarce. The aim of the present study
      was therefore to investigate objectively assessed sleep in pre-schoolers
      longitudinally, and to predict sleep, psychological functioning and cortisol
      secretion prospectively as a function of sleep 12 months earlier. METHOD: A total
      of 58 pre-schoolers (mean age: 5.43 years; 47% females) were re-assessed 12
      months later (mean age: 6.4 years). Sleep-EEG recordings were performed, saliva
      cortisol was analysed, and parents and experts rated children's psychological
      functioning. RESULTS: Longitudinally, poor objective sleep at age 5.4 years was
      associated with poor objective sleep and psychological difficulties but not
      cortisol secretion 12 months later. At age 6.4 years, poor sleep was concurrently
      associated with greater psychological difficulties and increased cortisol
      secretion. CONCLUSION: In pre-schoolers, poor sleep objectively assessed at the
      age of 5.4 years was associated with poor sleep and psychological difficulties
      one year later. Data indicate that in pre-schoolers, sleep remains stable over a
      12-months-period. Pre-schoolers with poor sleep appear to be at risk for
      developing further psychological difficulties.

PMID- 24011864
TI  - Congestive heart failure as a determinant of postoperative delirium.
AB  - BACKGROUND: Postoperative delirium (POD) is a frequent post-surgical complication
      that is associated with increased mortality and poor patient outcomes. POD is a
      complex disorder with multiple risk factors such as pre-existing patient
      comorbidities and perioperative complications. The aim of this study was to
      evaluate the incidence of POD and to identify risk factors for the development of
      POD in a post-anesthesia care unit (PACU). METHODS: We enrolled 97 adult patients
      admitted to a PACU over a five-day period (start date September 6, 2010). Patient
      demographics and intraoperative and postoperative data were collected. Patients
      were followed for the development of delirium using the Intensive Care Delirium
      Screening Checklist. Descriptive analyses of variables were used to summarize
      data, and the Mann-Whitney U test was used to compare continuous variables; the
      chi-square or Fisher's exact test was used for comparisons. Univariate analysis
      was performed using simple binary logistic regression with odds ratios (OR) and
      95% confidence intervals (95% CI). The significance level for multiple
      comparisons was controlled by applying the Bonferroni correction for multiple
      comparisons and variables were deemed significant if p<=0.0025. RESULTS: Six
      percent of patients developed POD. These patients were older and more likely to
      have higher American Society of Anesthesiologists (ASA) physical status (83 vs.
      22% with ASA III/IV, p=0.004) as well as a higher frequency of congestive heart
      failure (50 vs. 3%, p=0.003) and a higher Revised Cardiac Risk Index (RCRI) score
      (33 vs. 6% with RCRI >=2, p=0.039). The duration of anesthesia for patients with
      POD was also longer and they received a greater volume of crystalloids, colloids,
      and erythrocytes during surgery. Congestive heart disease was an independent risk
      factor for POD (OR 29.3, 95% CI 4.1-210.6; p<0.001). In addition, patients who
      developed POD had higher in-hospital mortality and longer PACU and hospital
      stays. CONCLUSIONS: Patients who developed POD had longer hospital and PACU stays
      and higher in-hospital mortality. Congestive heart disease was considered an
      independent risk factor for POD.

PMID- 24011865
TI  - [Heart failure with preserved ejection fraction: A moving target].

PMID- 24011866
TI  - Lithium toxicity presenting as transient transcortical motor aphasia: a case
      report.

PMID- 24011867
TI  - Targeting cyclin-dependent kinases in anti-neoplastic therapy.
AB  - Cell cycle progression is controlled by sequential activation of cyclin-dependent
      kinases (CDKs), which are often deregulated in cancer. Consequently numerous
      pharmacological inhibitors of CDKs have been developed with the aim of treating
      cancers. The article briefly reviews CDK inhibitors and their use to treat
      cancers, with specific focus on the use of biomarkers and drugs combination to
      improve their therapeutic efficacy. 

PMID- 24011868
TI  - Tall tales, myths, and things that go bump in the night.

PMID- 24011869
TI  - Radiological, clinical and histological correlations in a right segmental omental
      infarction due to primary torsion in a child.

PMID- 24011870
TI  - Functional imaging of cerebral perfusion.
AB  - The functional imaging of perfusion enables the study of its properties such as
      the vasoreactivity to circulating gases, the autoregulation and the neurovascular
      coupling. Downstream from arterial stenosis, this imaging can estimate the
      vascular reserve and the risk of ischemia in order to adapt the therapeutic
      strategy. This method reveals the hemodynamic disorders in patients suffering
      from Alzheimer's disease or with arteriovenous malformations revealed by
      epilepsy. Functional MRI of the vasoreactivity also helps to better interpret the
      functional MRI activation in practice and in clinical research. 

PMID- 24011871
TI  - Child maltreatment and adult health in a national sample: heterogeneous
      relational contexts, divergent effects?
AB  - OBJECTIVE: This study considers the long-term health consequences of child
      maltreatment. Distinct from previous research, we examine the effects of
      maltreatment in the context of more general parental evaluations. METHOD:
      Analyses used retrospective and current data from the Midlife Development in the
      United States (MIDUS) study. RESULTS: A considerable proportion of middle- and
      older-age adults who experienced frequent maltreatment nevertheless evaluated the
      relationship with their offending parent as "excellent", "very good", or "good"
      (e.g., 47% for physical and emotional maltreatment by mothers). Maltreated
      respondents generally evaluated their maltreating parents less favorably than non
      maltreating parents, but there was considerable variation in these recollected
      relationships. Adults who experienced child maltreatment reported a greater
      number of chronic medical conditions and physical symptoms and lower self-rated
      health, but effects were smaller when they had positive relationships with their
      parents than when one or more of the relationships was perceived as negative.
      CONCLUSIONS: These findings highlight a common and seemingly paradoxical pattern
      among MIDUS participants: the co-presence of harsh parental behavior and positive
      recollections of parental relationships during childhood. Moreover, these
      surprising patterns of retrospective interpretation predict very different
      experiences of adult health - health problems are most pronounced among
      maltreatment in cases where the respondent had a generally negative relationship
      with one or more of his or her parents.

PMID- 24011872
TI  - Effects of adding statins before surgery on mortality and major morbidity: a meta
      analysis.
AB  - OBJECTIVE: To re-evaluate the effects of adding a statin before surgery on
      mortality at 30 days and at 1 year and on major morbidity at 0-30 days. DESIGN: A
      meta-analysis of parallel, randomized, controlled trials published in English.
      SETTING: A university-based electronic search. PARTICIPANTS: Adult patients
      undergoing any type of procedure. INTERVENTION: Adding a statin before a
      procedure compared to a placebo or no intervention. MEASUREMENTS AND MAIN
      RESULTS: A search for all randomized controlled trials (RCT) was done in PubMed,
      Embase, Ovid MEDLINE and the Cochrane Central Register of Controlled Trials in
      November 2012. The quality of each study was assessed with the Cochrane
      Collaboration Tools. An I-square >= 25% was chosen as the cut-off point for
      heterogeneity exploration. The search produced 29 trials. Statins reduced the 0
      30 days' risk of myocardial infarction: risk ratio (RR) 0.48 (95%CI 0.38, 0.61);
      I-square 13.2%; p<0.001; number needed-to-treat 17 (14, 24). There were no
      statistical differences at 0-30 days for stroke RR 0.70 (0.25, 1.95), acute renal
      insufficiency RR 0.54 (0.26, 1.12) or reoperation RR 1.10 (0.51, 2.38). There was
      a trend for a reduced mortality at 1 year RR 0.26 (0.06, 1.02); I-square 0%; p =
      0.053. The hospital length of stay was slightly decreased with atorvastatin:
      standardized mean difference (SMD) -0.27 (-0.39, -0.14), p<0.001; fluvastatin SMD
      -0.95 (-1.56, -0.34), p = 0.002; and rosuvastatin SMD -0.69 (-0.98, -0.40),
      p<0.001 but not with simvastatin SMD -0.04 (-0.41, 0.48). CONCLUSIONS: Adding a
      statin before a high risk cardiac procedure reduces the 0-30 days' risk of
      myocardial infarction.

PMID- 24011873
TI  - Isolated high lactate or low central venous oxygen saturation after cardiac
      surgery and association with outcome.
AB  - OBJECTIVE: To determine if isolated abnormally low central venous oxygen
      saturation (ScvO2) or elevated lactate levels on admission to an intensive care
      unit (ICU) are associated with increased morbidity and length of stay (LOS) after
      cardiac surgery. DESIGN: Retrospective, observational. SETTING: Academic tertiary
      care hospital. PARTICIPANTS: Six hundred twenty-nine adult, on-pump cardiac
      surgery patients with ScvO2 and arterial lactate obtained on admission to the
      ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Comparing outcomes
      across the isolated low ScvO2 and high lactate categories, no significant
      differences in ICU/hospital LOS, ICU readmission rate, length of mechanical
      ventilation, or incidence of major complications were observed in patients with
      ScvO2<70% and lactate < 2 mmol/L or in those with lactate 2-3.9 mmol/L and ScvO2
      >= 70%. However, patients with lactate >= 4 mmol/L and ScvO2 >= 70% exhibited
      significantly longer median ICU LOS (p = 0.018), hospital LOS (p = 0.032), length
      of mechanical ventilation (p = 0.0001), and higher incidence of major
      complications (p = 0.008). Multivariate analysis identified isolated elevated
      lactate levels >= 4 mmol/L as an independent predictor for major complications
      (OR 4.29, p = 0.0008). CONCLUSIONS: Low ScvO2 with normal lactate or moderately
      elevated lactate with normal ScvO2 upon ICU admission after cardiac surgery was
      not associated with increased morbidity or length of stay. Markedly elevated
      lactate levels in the setting of a normal ScvO2 was associated with significantly
      higher incidence of major complications and prolonged length of stay.
      Additionally, a lactate level >= 4 mmol/L was an independent predictor of major
      complications.

PMID- 24011874
TI  - Aorta-right atrial tunnel: imaging and surgical repair in an adult patient.

PMID- 24011875
TI  - Dynamic indices of mitral valve function using perioperative three-dimensional
      transesophageal echocardiography.
AB  - OBJECTIVE: Perioperative transesophageal echocardiography is essential for
      decision-making for mitral valve surgery. While two-dimensional transesophageal
      echocardiography represents the standard of care, tracking of dynamic changes
      using three-dimensional imaging permits assessment of morphologic and functional
      characteristics of the mitral valve. The authors hypothesized that quantitative
      three-dimensional analysis would reveal distinct differences among diseased,
      repaired, and normal mitral valves. DESIGN: Case-control observational clinical
      study. SETTING: Tertiary care hospital. PARTICIPANTS: Using novel mitral valve
      quantification software, the authors retrospectively analyzed 80 datasets of
      cardiac surgery patients who underwent intraoperative transesophageal
      echocardiographic imaging. Twenty patients with degenerative mitral regurgitation
      were evaluated before and after mitral valve repair. Twenty patients had
      functional mitral regurgitation, and 20 patients had no mitral valve disease.
      MEASUREMENTS AND MAIN RESULTS: Primary outcome measures of dynamic mitral valve
      function were: 1) three-dimensional annulus area, 2) annular displacement
      distance, 3) annular displacement velocity, and 4) annular area fraction. Other
      mitral annular tracking indices, in addition to intraobserver reliability and
      interobserver agreement, also were reported. Annulus area was enlarged in
      degenerative and functional mitral regurgitation. Annular displacement distance
      was decreased in functional mitral regurgitation and repaired valves. Annular
      displacement velocity was decreased in functional mitral regurgitation. Annular
      area fraction was decreased in functional mitral regurgitation and repaired
      valves. Intraobserver reliability and interobserver agreement were high for all 4
      analyzed indices. CONCLUSIONS: Normal, functional regurgitant, degenerative, and
      repaired mitral valves have distinctly different dynamic signatures of anatomy
      and function as reliably determined by perioperative echocardiographic tracking.

PMID- 24011876
TI  - An uncommon perspective on a common congenital anomaly.

PMID- 24011877
TI  - Malignant hyperthermia-like manifestations in a two-month-old child with Holt
      Oram syndrome undergoing cardiac surgery.

PMID- 24011878
TI  - Propofol-based versus dexmedetomidine-based sedation in cardiac surgery patients.
AB  - OBJECTIVES: To evaluate the effects of propofol-based and dexmedetomidine-based
      sedation regimens on achieving early extubation, length of stay (LOS), intensive
      care length of stay (ICU-LOS), total hospital costs, and mortality rates in
      cardiac surgery patients. DESIGN: Twenty-three-month retrospective analysis.
      SETTING: Single center, 907 bed community teaching hospital. PARTICIPANTS: Five
      hundred eighty-two patients >= 18 years of age who received propofol-based or
      dexmedetomidine-based sedation after cardiac valve or coronary artery bypass
      grafting (CABG) surgery and who did not undergo prolonged surgery (<= 8 hours).
      INTERVENTION: Retrospective review of medical records. MEASUREMENTS AND MAIN
      RESULTS: Baseline characteristics (eg, age, sex, comorbidities) and outcomes (eg,
      achievement of early extubation, LOS, ICU-LOS, total hospital costs, pharmacy
      costs) were collected. Early extubation was achieved more frequently in the
      dexmedetomidine group when compared with the propofol group (68.7% v 58.1%, p =
      0.008). The mean postoperative time to extubation and hospital LOS were shorter
      in the dexmedetomidine group when compared with the propofol group (8.8 v 12.8
      hours, p = 0.026) and (181.9 v 221.3 hours, p = 0.001), respectively. There was a
      reduced ICU-LOS in the dexmedetomidine group compared with the propofol group
      that did not reach statistical significance (43.9 v 52.5 hours, p = 0.067).
      Average total hospital charges for the dexmedetomidine group were approximately
      $4000.00 less than the propofol group. CONCLUSIONS: Dexmedetomidine-based
      sedation resulted in achievement of early extubation more frequently than
      propofol-based sedation. Mean postoperative time to extubation and average
      hospital LOS were shorter with dexmedetomidine-based sedation and met a
      statistical level of significance. There was no difference in ICU-LOS or in
      hospital mortality between the two groups. Total hospital charges were similar,
      although slightly higher in the propofol group.

PMID- 24011879
TI  - Sex steroids and variants of gender identity.
AB  - This article summarizes for the practicing endocrinologist the current literature
      on the psychobiology of the development of gender identity and its variants in
      individuals with disorders of sex development (DSD) or with non-DSD
      transgenderism. Gender reassignment remains the treatment of choice for strong
      and persistent gender dysphoria in both categories, but more research is needed
      on the short-term and long-term effects of puberty-suppressing medications and
      cross-sex hormones on brain and behavior. 

PMID- 24011880
TI  - Neuropsychiatric manifestations of thyroid disease.
AB  - The interface between thyroid hormone action and neuropsychiatric function is
      intricate, and several mechanisms of thyroid hormone uptake into brain tissues,
      hormone activation, and influences on neurotransmitter generation have been
      identified. Symptoms of hypothyroidism are nonspecific, whereas those attributed
      to thyrotoxicosis may be more characteristic. Neuropsychiatric manifestations
      triggered by thyroid dysfunction likely respond well to reestablishment of the
      euthyroid state, although some patients have persistent complaints. The addition
      of LT3 to ongoing LT4 replacement has yet to be definitively shown to be
      advantageous. Treatment of euthyroid depression with LT3 in addition to
      antidepressant therapy lacks convincing evidence of superior outcomes. 

PMID- 24011881
TI  - Neuropsychiatric findings in Cushing syndrome and exogenous glucocorticoid
      administration.
AB  - This article reviews the neuropsychiatric presentations elicited by spontaneous
      hypercortisolism and exogenous supraphysiologic glucocorticoids. Patients with
      Cushing disease and syndrome develop a depressive syndrome: irritable and
      depressed mood, decreased libido, disrupted sleep and cognitive decrements.
      Exogenous short-term glucocorticoid administration may elicit a hypomanic
      syndrome with mood, sleep and cognitive disruptions. Treatment options are
      discussed. Brain imaging and neuropsychological studies indicate elevated
      cortisol and other glucocorticoids are especially deleterious to hippocampus and
      frontal lobe. The research findings also shed light on neuropsychiatric
      abnormalities in conditions that have substantial subgroups exhibiting elevated
      and dysregulated cortisol: aging, major depressive disorder and Alzheimer's
      disease. 

PMID- 24011883
TI  - Endocrine aspects of post-traumatic stress disorder and implications for
      diagnosis and treatment.
AB  - Post-traumatic stress disorder (PTSD) is a serious, multisystem disorder with
      multiple medical comorbidities. This article reviews the current literature on
      the endocrine aspects of PTSD, specifically hypothalamic-pituitary-adrenal axis
      alterations indicative of low cortisol and increased glucocorticoid sensitivity,
      and the proposed mechanisms whereby these alterations increase risk or reflect
      pathophysiology. Discussion includes novel treatment innovations and directions
      for future research. 

PMID- 24011882
TI  - Type 2 diabetes and cognitive compromise: potential roles of diabetes-related
      therapies.
AB  - Type 2 diabetes, like dementia, disproportionately affects the elderly. Diabetes
      has consistently been associated with risk of dementia, mild cognitive
      impairment, and cognitive decline suggesting that cognitive compromise is a
      deleterious manifestation of diabetes. This review summarizes observational
      studies and clinical trials of diabetes medications and their respective
      associations and effects on cognitive outcomes. Despite biological plausibility,
      results from most human clinical trials have failed to show any efficacy in
      treating Alzheimer disease symptomatology and pathology. Clinical trials
      targeting vascular-related outcomes, diabetic patients, or cognitively normal
      elderly at risk for dementia, may provide greater cognitive benefits. 

PMID- 24011885
TI  - Adverse effects of depression on glycemic control and health outcomes in people
      with diabetes: a review.
AB  - In the past decades, important advances have been achieved in the psychological
      aspects of diabetes. This article reviews the associations between diabetes,
      depression, and adverse health outcomes. The article provides an update on the
      literature regarding the prevalence of depression in diabetes, discusses the
      impact of depression on diabetes self-care and glycemic control in people with
      diabetes, and summarizes the results of longitudinal studies that have
      investigated depression as a risk factor for adverse health outcomes. 

PMID- 24011884
TI  - Endocrine effects of anorexia nervosa.
AB  - A key feature of anorexia nervosa, a disease primarily psychiatric in origin, is
      chronic starvation, which results in profound neuroendocrine dysregulation,
      including hypogonadism, relative growth hormone resistance, and
      hypercortisolemia. A recent area of investigation is appetite hormone
      dysregulation. Whether such dysregulation is compensatory or plays a role in the
      pathophysiology of anorexia nervosa is incompletely understood. The primary
      therapy for anorexia remains psychiatric, and endocrine abnormalities tend to
      improve with weight restoration, although residual endocrine dysfunction can
      occur. In addition, therapies directed at specific complications have been a
      particular focus of research. 

PMID- 24011886
TI  - Effects of antipsychotic medications on appetite, weight, and insulin resistance.
AB  - Although clozapine, olanzapine, and other atypical antipsychotic drugs (APDs)
      have fewer extrapyramidal side effects, they have serious metabolic side effects
      such as substantial weight gain, intra-abdominal obesity, and type 2 diabetes
      mellitus. Given that most patients with mental disorders face chronic, even life
      long, treatment with APDs, the risks of weight gain/obesity and other metabolic
      symptoms are major considerations for APD maintenance treatment. This review
      focuses on the effects of APDs on weight gain, appetite, insulin resistance, and
      glucose dysregulation, and the relevant underlying mechanisms that may be help to
      prevent and treat metabolic side effects caused by APD therapy. 

PMID- 24011887
TI  - The impact of traumatic brain injury on pituitary function.
AB  - It is paramount that clinicians who care for patients with traumatic brain injury
      (TBI) at any point in time, including neurosurgeons, rehabilitation physicians,
      internists, neurologists, and endocrinologists, are aware of the prevalence of
      posttraumatic hypopituitarism and its impacts on acute and long-term recovery.
      This article reviews the natural history, pathophysiology, and presenting
      features of hypopituitarism occurring after TBI. Proposed methodologies for
      screening, diagnosis, and initiation of treatment are discussed, as well as the
      effect of hormone replacement therapy on clinical outcomes. 

PMID- 24011888
TI  - Drug addiction and sexual dysfunction.
AB  - This article attempts to review the most current and the well-established facts
      concerning drug addiction and sexual dysfunction. Surprisingly, even though
      alcohol is prevalent in many societies with many myths surrounding its sexual
      enhancing effects, current scientific research cannot provide a solid conclusion
      on its effect on sexual function. Unfortunately, the same concept applies to
      tobacco smoking; however, most of the current knowledge tends to support the
      notion that it, indeed, can negatively affect sexual function. Similar
      ambiguities also prevail with substances of abuse. 

PMID- 24011891
TI  - Bidirectional impact of endocrine disorders.

PMID- 24011889
TI  - Effects of alcohol on the endocrine system.
AB  - Chronic consumption of a large amount of alcohol disrupts the communication
      between nervous, endocrine, and immune system and causes hormonal disturbances
      that lead to profound and serious consequences at physiologic and behavioral
      levels. These alcohol-induced hormonal dysregulations affect the entire body and
      can result in various disorders such as stress abnormalities, reproductive
      deficits, body growth defect, thyroid problems, immune dysfunction, cancers, bone
      disease, and psychological and behavioral disorders. This review summarizes the
      findings from human and animal studies that provide consistent evidence on the
      various effects of alcohol abuse on the endocrine system. 

PMID- 24011892
TI  - Critical relationships between endocrine and neuropsychiatric disorders.

PMID- 24011890
TI  - Sleep disorders and the development of insulin resistance and obesity.
AB  - Normal sleep is characterized both by reduced glucose turnover by the brain and
      other metabolically active tissues, and by changes in glucose tolerance. Sleep
      duration has decreased over the last several decades; data suggest a link between
      short sleep duration and type 2 diabetes. Obstructive sleep apnea (OSA) results
      in intermittent hypoxia and sleep fragmentation, and also is associated with
      impaired glucose tolerance. Obesity is a major risk factor for OSA, but whether
      OSA leads to obesity is unclear. The quality and quantity of sleep may profoundly
      affect obesity and glucose tolerance, and should be routinely assessed by
      clinicians. 

PMID- 24011893
TI  - Theoretical investigation on the mechanisms and kinetics of OH-initiated
      photooxidation of dimethyl phthalate (DMP) in atmosphere.
AB  - The atmospheric OH-initiated degradation mechanisms of dimethy phthalate (DMP)
      are analyzed at the MPWB1K/6-311++G(3df,2p)//MPWB1K/6-31+G(d,p) level of theory.
      The principal products detected experimentally are confirmed by this study while
      several major intermediates are reported for the first time. Additionally, the
      pathway scheme of hydroxylation reaction of DMP is proposed. The results about
      initial steps indicate that hydroxyl radical is most likely to be added to the
      ortho-carbon atom among additional reactions, while H atoms in methyl group are
      the most favorable to be abstracted by the OH radical. The rate constants of the
      elementary reactions over the temperature of 200-400 K were deduced using RRKM
      theory. The overall rate constant of the title reaction is 1.18*10(-12) cm(3)
      molecule(-1) s(-1) at 298 K and 760 Torr while H abstraction reactions
      predominate. According to the rate constants given at different temperatures, the
      Arrhenius equation is fitted. The atmospheric half life of DMP with respect to OH
      is estimated to be 6.8 days.

PMID- 24011894
TI  - Arbuscular mycorrhizal fungi enhance both absorption and stabilization of Cd by
      Alfred stonecrop (Sedum alfredii Hance) and perennial ryegrass (Lolium perenne
      L.) in a Cd-contaminated acidic soil.
AB  - A greenhouse pot experiment was conducted to compare the phytoextraction
      efficiencies of Cd by hyper-accumulating Alfred stonecrop (Sedum alfredii Hance)
      and fast-growing perennial ryegrass (Lolium perenne L.) from a Cd-contaminated
      (1.6 mg kg(-1)) acidic soil, and their responses to the inoculations of two
      arbuscular mycorrhizal (AM) fungal strains, Glomus caledonium 90036 (Gc) and
      Glomus mosseae M47V (Gm). Ryegrass and stonecrop were harvested after growing for
      9 and 27 wk, respectively. Without AM fungal inoculation, the weekly Cd
      extraction by stonecrop (8.0 MUg pot(-1)) was 4.3 times higher than that by
      ryegrass (1.5 MUg pot(-1)). Both Gc and Gm significantly increased (P < 0.05)
      root mycorrhizal colonization rates, soil acid phosphatase activities, and
      available P concentrations, and thereby plant P absorptions (except for Gm
      inoculated ryegrass), shoot biomasses, and Cd absorptions (except for Gm
      inoculated stonecrop), while only Gc-inoculated stonecrop significantly
      accelerated (P < 0.05) the phytoextraction efficiency of Cd by 78%. In addition,
      both Gc and Gm significantly decreased (P < 0.05) phytoavailable Cd
      concentrations by 21-38% via elevating soil pH. The results suggested the
      potential application of hyper-accumulating Alfred stonecrop associated with AM
      fungi (notably Gc) for both extraction and stabilization of Cd in the in situ
      treatment of Cd-contaminated acidic soil.

PMID- 24011895
TI  - Formation of N-nitrosamines by chloramination or ozonation of amines listed in
      Pollutant Release and Transfer Registers (PRTRs).
AB  - We determined whether or not the chloramination or ozonation of amines and
      hydrazines listed in Pollutant Release and Transfer Registers (PRTRs) results in
      the formation of N-nitrosamines when reacted in secondary wastewater effluent. We
      selected 12 primary, 2 secondary, 2 tertiary amines and 3 hydrazines from the
      PRTRs of Japan, the USA, and Korea. In this study, based on the assumption that
      there is a production of N-nitrosamines by not only the original selected amines
      and hydrazines but also the intermediate products in case of chloramination and
      ozonation, it was examined whether precursors were identified by selected amines
      and hydrazines based on the gap of the N-nitrosamines formation potential between
      day 0 and day 10 rather than analyzing the contribution depending on the
      concentration of selected amines and hydrazines. Many of the primary amines
      (notably 2,6-xylidine) and all of the secondary and tertiary amines produced N
      nitrosodimethylamine (NDMA) by chloramination. Furthermore, the primary amines
      2,6-xylidine, 3,3'-dimethylbenzidine, 4,4'-methylenebis(2-chloroaniline), 4
      aminoazobenzene, p-chloroaniline, and p-cresidine produced more NDMA than did the
      secondary amines. The secondary amines produced mainly NDMA. Ozonation produced
      NDMA only from the hydrazine 1,1-dimethylhydrazine, and at a higher concentration
      than by chloramination. We identified 2,6-xylidine, 3,3'-dimethylbenzidine, 4,4'
      methylenebis(2-chloroaniline), 4-aminoazobenzene, p-chloroaniline, p-cresidine,
      1,1-dimethylhydrazine, diethylamine, 4,4'-methylenebis(N,N-dimethyl)benzenamine,
      and chinomethionat as warranting further study. 

PMID- 24011896
TI  - Formation potential of nine nitrosamines from corresponding secondary amines by
      chloramination.
AB  - Nitrosamines, a group of emerging disinfection by-products (DBPs) in drinking
      water, have recently caused significant concern because of their higher
      carcinogenic potential than that of currently regulated DBPs. In this study, the
      formation of nine representative nitrosamines by chloramination of their
      corresponding secondary amines was investigated under various conditions. All
      nine nitrosamines were detected in the corresponding reaction solutions, which
      confirmed that all the investigated secondary amines were the potential
      precursors of corresponding nitrosamines. The molar yields of nitrosamines from
      the corresponding secondary amines were quite different, depending on the
      structural characteristics of the secondary amines. The maximum molar yields for
      the formation of all nine nitrosamines occurred in the pH range of 7.0-9.0 and at
      the Cl/N molar ratio of 0.7 for chloramines, suggesting that monochloramine and
      unprotonated secondary amines may play a major role in the formation of
      nitrosamines. The molar yields of nitrosamines also exhibited a moderate upward
      tendency with rising temperature, but no consistent correlation was observed
      between the formation of nitrosamine and the initial concentrations of secondary
      amines and chloramines. The results of this study could be useful for devising
      strategies for controlling the formation of nitrosamines during the disinfection
      processes of drinking water. 

PMID- 24011897
TI  - Portuguese inventory of dioxins and furans atmospheric emissions.
AB  - This article presents the results of the most recent estimation of
      polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (PCDF) atmospheric
      emissions in Portugal, which has covered the period 2004-2009 and includes 27
      emission sources types. The results are compared with previous emissions
      inventories published for Portugal. The main objective of this work is to provide
      relevant information about the amounts of the compounds that are released into
      the atmosphere in Portugal, and identify their major sources and trends. The
      methodology involved the identification of relevant sources, the collection of
      information to characterize these sources, the selection of appropriate emission
      factors and their application to estimate the emissions. Furthermore, several
      studies conducted in Portugal were considered, namely reports from PCDD/PCDF
      measurements performed in some industrial facilities. The inventory covered 27
      emission sources types. However the results show that only 8 were relevant, i.e.
      with emission amounts greater than 1 g I-TEQ year(-1). The total emissions of
      PCDD/PCDF in Portugal reached between 40 and 105 g I-TEQ year(-1), for the period
      of 2004-2009. The largest emission source and at same time with greater variation
      is forest fires, with emissions between 3 g I-TEQ year(-1) and 67 g I-TEQ year(
      1) in 2008 and 2005, respectively. Excluding the emissions from forest fires, the
      total emission is more or less constant over the years and around 37 g I-TEQ
      year(-1).

PMID- 24011898
TI  - Effects of sterile storage, cation saturation and substrate additions on the
      degradability and extractability of nonylphenol and phenanthrene in soil.
AB  - The main objective of this study was to determine the effects of long-term
      abiotic processes during aging of organic pollutants in soil on their microbial
      degradability and formation of non-extractable residues. The specific aims of our
      study were to investigate how the fate of p353-nonylphenol (NP) and phenanthrene
      (Phe) in soils might be affected by: (i) saturation of soil by cations with
      different valency (Na(+), Ca(2+) or Al(3+)), (ii) addition of organic substrate
      (wood flour) during incubation period and (iii) different soil moisture levels.
      This study showed positive effect of long-term aging of sterilized samples on
      respiration of re-inoculated samples. However, the lack of aging effects on the
      mineralization of NP and Phe indicates that slow sorption processes by diffusion
      into less bioaccessible domains were not relevant in studied soils. Similarly,
      the lower respiration and xenobiotic mineralization rates in the Na(+) and Al(3+)
      treated soils indicate that this is due to toxic effects on microbial activity
      and not due to xenobiotic accessibility. Instead, the formation of non
      extractable residues was strongly promoted by biological activity, most likely
      through formation of more reactive metabolites. The addition of wood flour
      greatly stimulated microbial respiration and enhanced NP mineralization while
      inhibiting that of Phe. Along with negligible effect of water addition after 4
      weeks of incubation on kinetics of soil respiration, the soil moisture effect on
      xenobiotics mineralization indicates that most probably the bioavailability of NP
      and Phe increased due to bridging role of water films in soil.

PMID- 24011899
TI  - How UK obstetric anaesthetists assess neuraxial anaesthesia for caesarean
      delivery: national surveys of practice conducted in 2004 and 2010.
AB  - BACKGROUND: There is much interest in optimal methods of assessing neuraxial
      block before caesarean delivery. Although cold sensation is commonly used, some
      evidence suggests that the risk of intraoperative pain may be reduced by
      assessing light touch. We aimed to determine how neuraxial anaesthesia was
      managed perioperatively, and whether changes in clinical practice reflected the
      differing evidence in the literature over six years. METHODS: A survey was sent
      to UK consultant OAA members in 2004, asking how neuraxial block was assessed
      before caesarean delivery, what was documented, what information was given to the
      patient, and postoperative follow-up. The survey was repeated in 2010. RESULTS:
      Compared to all other methods of assessing neuraxial block, ethyl chloride was
      the most popular in 2004 (71.8%, 95% CI 68.3-75.0, P < 0.0001) and 2010 (74.6%,
      95% CI 70.8-78.3, P < 0.0001). There was a non-significant increase in light
      touch use from 54% to 60.1%. The upper level of block varied with the modality
      tested. There was a significant increase in respondents testing with light touch
      to T5. CONCLUSIONS: Methods of assessing neuraxial block differed from those
      recommended in the literature. The wide range of modalities, methods of testing
      and targeted sensory levels suggest that clearer recommendations on best practice
      for assessment and documentation of neuraxial block before caesarean delivery are
      required.

PMID- 24011900
TI  - Alcohol intake and brain structure in a multiethnic elderly cohort.
AB  - BACKGROUND & AIMS: Evidence suggests that consuming light-to-moderate amounts of
      alcohol reduces the risk of dementia and is associated better cognitive function
      and less cardiovascular disease, relative to those consuming no or heavy alcohol.
      There are only minimal data on the association between alcohol and brain magnetic
      resonance imaging (MRI) markers. This study aimed to examine the association
      between alcohol and brain structure measured with MRI. METHODS: In this cross
      sectional study, high-resolution structural MRI was collected on 589 multi-ethnic
      community residents of New York aged >=65 with available alcohol intake
      assessments via a food frequency questionnaire. Total brain volume (TBV), white
      matter hyperintensity volume (WMHV), and presence of infarcts were derived from
      MRI scans with established methods. We examined the association of alcohol intake
      with these imaging markers using regression models adjusted for demographic,
      clinical, and vascular risk factors. RESULTS: Compared to non-drinking, light-to
      moderate total alcohol (b = 0.007, p = 0.04) or wine (b = 0.008, p = 0.05)
      intake, but not beer or liquor intake, was associated with larger TBV. Further
      analysis showed a dose-response association between alcohol (p-trend = 0.03) or
      wine (p-trend = 0.006) and TBV. Overall, alcohol intake was not associated with
      WMHV or brain infarcts. CONCLUSIONS: Our study suggests that among older adults
      in the community, light-to-moderate alcohol intake, in particular wine, is
      associated with larger TBV. These findings suggest that light to moderate alcohol
      consumption is potentially beneficial for brain aging, but replication is needed.

PMID- 24011901
TI  - An investigation of the role of soluble CD14 in hospitalized, sick horses.
AB  - The objectives of this study were to (1) evaluate the effects of equine soluble
      CD14 (sCD14) and monoclonal antibodies (mAb) to equine CD14 on lipopolysaccharide
      induced tumor necrosis factor alpha (TNF-alpha) secretion from equine peripheral
      blood mononuclear cells (PBMC); and to (2) determine serum concentrations of
      sCD14 in a population of horses with gastrointestinal diseases or other illnesses
      likely to result in endotoxemia. Equine PBMC isolated from 10 healthy horses were
      incubated with Escherichia coli LPS plus CD14 mAb or sCD14 and assayed for TNF
      alpha activity. Pre-incubation with CD14 mAb did not inhibit LPS-induced TNF
      alpha production, whereas use of sCD14 inhibited LPS-induced TNF-alpha production
      in a concentration-dependent manner. Additionally, blood samples from 55 ill and
      23 healthy horses were used to determine serum concentrations of sCD14.
      Concentrations of sCD14 were positively correlated to respiratory rate, duration
      of clinical signs and band neutrophil count. Although serum sCD14 was
      significantly increased in the ill horses compared to healthy horses, sCD14 did
      not correlate with outcome. Results of this study indicate that release of sCD14
      is increased in ill horses and that TNF-alpha production by PBMC is decreased
      when cells are treated with sCD14. 

PMID- 24011902
TI  - Helicobacter spp. infection induces changes in epithelial proliferation and E
      cadherin expression in the gastric mucosa of pigs.
AB  - Gastric disease is common in finishing pigs. Helicobacter spp. infection has been
      associated with gastritis, gastric ulcers and gastric neoplasia in man and
      animals. The aim of this study was to determine the effects of Helicobacter spp.
      infection on gastric morphology in pigs, with emphasis on glandular cell
      proliferation and E-cadherin expression. Samples of fundus and antrum from 67
      finishing pigs were examined microscopically and by immunohistochemistry. The
      presence of Helicobacter spp. was confirmed by polymerase chain reaction (PCR).
      Mucosal changes were evaluated and epithelial proliferation was determined by
      evaluation of the morphometry of nucleolar organizer regions and counting
      proliferating cell nuclear antigen-positive cells and mitotic figures.
      Intercellular adhesion was evaluated by E-cadherin expression. In 47 (70%) pigs,
      Helicobacter spp. infection was confirmed by PCR. Histological findings
      associated with the infection included mononuclear cell infiltration of the
      lamina propria and glandular degeneration. There was a significant association
      between infection and epithelial proliferation in both regions as well as a
      decrease in the expression of E-cadherin in the antrum. 

PMID- 24011903
TI  - Occurrence of tumours metastatic to bones and multicentric tumours with skeletal
      involvement in dogs.
AB  - The skeletons of 110 dogs with malignant tumours of different origins were
      examined by necropsy examination over a 3-year period to identify bone
      metastases. Twenty-one cases of metastatic or multicentric tumours with bone
      involvement were recorded. In general, more female dogs presented with bony
      metastases; however, when the dogs with mammary tumours were omitted, the gender
      distribution of the cases was approximately equivalent. The mammary gland was the
      primary site of most of the metastatic bone lesions, followed by the
      musculoskeletal system and the respiratory system. The majority (77%) of
      metastases were grossly visible and present in multiple bones. However, in 23% of
      the cases, the metastases could be diagnosed only at the microscopical level. The
      vertebrae and the humerus were the most frequently affected bones regardless of
      the primary site and the histogenesis of the tumours. The results of this study
      revealed a high prevalence of bone metastases and/or bone involvement in dogs
      with multicentric tumours.

PMID- 24011904
TI  - Nasal and cutaneous aspergillosis in a goat.
AB  - Nasal and cutaneous aspergillosis is reported in an adult goat. The clinical
      signs were severe respiratory distress due to partial nasal obstruction,
      bilateral mucopurulent nasal discharge, skin nodules on the ears and dorsal nasal
      region and focal depigmentation of the ventral commissure of the right nostril.
      At necropsy examination, sagittal sectioning of the head revealed a yellow
      irregular mass extending from the nasal vestibule to the frontal portion of the
      nasal cavity. Microscopically, there was pyogranulomatous rhinitis and
      dermatitis, with numerous intralesional periodic acid-Schiff-positive fungal
      hyphae morphologically suggestive of Aspergillus spp. Aspergillus niger was
      isolated by microbiological examination.

PMID- 24011905
TI  - Heterosporis anguillarum infection in a garter snake (Thamnophis sirtalis).
AB  - A captive garter snake (Thamnophis sirtalis) showed marked circumferential
      thickening of the body wall due to a chronic fibrous to necrotizing inflammatory
      reaction extending from the serosa to the skin. The lesions were associated with
      the presence of intra- and extracellular microsporidian organisms. With
      ultrastructural and molecular analyses the microsporidia were identified as
      Heterosporis anguillarum. This organism causes a morphologically similar disease
      in the Japanese eel (Anguilla japonica), but this is the first time it has been
      identified in an infected reptile. 

PMID- 24011906
TI  - Primitive neuroectodermal tumour in a striped dolphin (Stenella coeruleoalba)
      with features of ependymoma and neural tube differentiation (Medulloepithelioma).
AB  - Primary brain tumours in cetaceans are rare with only four reported cases of
      intracranial tumours in the scientific literature. A juvenile female, striped
      dolphin live-stranded at Whitepark Bay, Co Antrim, Northern Ireland, UK, and died
      after an unsuccessful attempt at refloatation. Necropsy examination revealed a
      large, soft, non-encapsulated friable mass, which expanded and replaced the
      frontal lobes, corpus callosum and caudate nucleus of the brain and extended into
      the lateral ventricles, displacing the thalamus caudally. Microscopically, this
      comprised moderately pleomorphic neoplastic cells arranged variably in dense
      monotonous sheets, irregular streams, ependymal rosettes, 'ependymoblastomatous
      rosettes' and multilayered to pseudostratified tubules. Liquefactive necrosis,
      palisading glial cells, haemorrhage and mineralization were also observed.
      Immunohistochemically, the neoplastic cells expressed vimentin but not S100,
      glial fibrillary acidic protein, cytokeratin, neuron-specific enolase or
      synaptophysin. Based on these findings a diagnosis of primitive neuroectodermal
      tumour was made. Monitoring and recording such cases is crucial as neoplasia may
      be related to viral, carcinogenic or immunosuppressive chemical exposure and can
      ultimately contribute to assessing the ocean health. 

PMID- 24011907
TI  - A hypothesis regarding the cause of the functional somatic syndrome and
      suggestions in regard to its validation.
AB  - This hypothesis states that if the lymphocytes from some patients diagnosed as
      having the functional somatic syndrome were observed in the scanning electron
      microscope as they reacted with brain cells thought to be involved with the
      somatic syndrome, that unique changes in the anatomy of the T-cells would be
      observed. 

PMID- 24011908
TI  - Local heat preconditioning in skin sparing mastectomy: a pilot study.
AB  - BACKGROUND: Experimental data has shown an association with a reduction of flap
      necrosis after local heat-application to a supraphysiological level resulting
      from the up-regulation of heat shock proteins, such as HSP-32. The proteins
      maintained capillary perfusion and increased tissue tolerance to ischaemia. The
      purpose of this translational study was to evaluate the effect of local heat
      preconditioning before skin sparing mastectomy and immediate breast
      reconstruction. METHODS: A prospective non-randomised trial was performed from
      July 2009-April 2010. 50 consecutive patients at risk of skin flap necrosis (BMI
      >30, sternal-to-nipple distance>26 cm or breast size>C-cup) were included. Twenty
      five patients were asked to heat-precondition their breast 24-h prior to surgery
      using a hot water bottle with a water temperature of 43  degrees C (thermometers
      provided), in three 30-min cycles interrupted by spontaneous cooling to room
      temperature. Skin flap necrosis was defined by the need for surgical debridement.
      LDI images were taken pre- and post-mastectomy to demonstrate an increase in
      tissue vascularity. RESULTS: 36% of women (n=25) without local heat-treatment
      developed skin flap necrosis, 12% developed skin flap necrosis in the treatment
      group, resulting in a 24% difference (n=25; p=0.047 (95%CI 1%-47%)). LDI scanning
      of the heated breast demonstrated an increase in vascularity compared to the
      contralateral non-heated breast. Median length of inpatient stay for treatment
      group was 4 days (95%CI(4, 7)), controls 8 days (95%CI(8, 9) (p=<0.001)).
      CONCLUSIONS: The data suggests that in selected cases, local heat preconditioning
      is a simple and non-invasive method of reducing skin necrosis and length of
      hospital stay following skin sparing mastectomy. CLINICAL TRIAL REGISTRATION
      NUMBER: ACTRN12612001197820. LEVEL OF EVIDENCE: II.

PMID- 24011909
TI  - Treatment of infantile haemangiomas with atenolol: comparison with a historical
      propranolol group.
AB  - Propranolol, a lipophilic non-selective beta-blocker, has proven to be effective
      in the treatment of infantile haemangioma (IH). However, several side effects
      have been reported. Atenolol, a hydrophilic selective beta-1 blocker, could be an
      alternative and associated with fewer side effects. Thirty consecutive patients
      with IH were treated with atenolol between June 2010 and May 2011. The
      therapeutic effect was judged by clinical assessment and quantified by using a
      visual analogue scale (VAS) and the Haemangioma Activity Score (HAS). Side
      effects were also evaluated. The atenolol cohort was compared with a previously
      described cohort of 28 patients treated with propranolol between July 2008 and
      December 2009. Clinical involution was present in 90% (27/30) of the IH patients
      treated with atenolol. Mild side effects occurred in 40% (12/30) of these
      patients and severe side effects occurred in 3% (1/30). Compared with the
      previously described cohort treated with propranolol, mild side effects occurred
      in 50% (14/28) and severe side effects in 25% (7/28) of the patients (p=0.04).
      Quantitative improvement of the IH in the atenolol group (n=27) showed no
      significant difference in either the VAS score or the HAS compared to the
      propranolol group (n=24). This study indicates that atenolol is effective in the
      treatment of IH. Compared with a historical control group treated with
      propranolol, the effects of atenolol seem to be similar and less frequently
      associated with severe side effects. Randomised clinical trials are necessary to
      evaluate the efficacy and safety of atenolol treatment in IH.

PMID- 24011910
TI  - First report of the use of transesophageal echocardiography to position a
      temporary pacing wire.

PMID- 24011911
TI  - Ability of the third-generation FloTrac/Vigileo software to track changes in
      cardiac output in cardiac surgery patients: a polar plot approach.
AB  - OBJECTIVE: To evaluate the ability of the third-generation (3.01) of
      FloTrac/Vigileo monitor (Edwards Lifesciences, Irvine, CA) to follow variations
      in cardiac output (?CO) using the new polar plot approach. DESIGN: Prospective
      interventional study. SETTING: Single hospital university study. PARTICIPANTS:
      Twenty-five patients referred for cardiac surgery. INTERVENTIONS: CO was measured
      simultaneously by 3 to 5 bolus thermodilution (COtd measurements), using a
      pulmonary artery catheter and by arterial pulse contour analysis, using the
      FloTrac/Vigileo (COvi). Data were collected at eight time points: before
      incision, after sternotomy, before and after protamine sulfate infusion, at the
      start of sternal closure, at the end of surgery, on arrival to intensive care
      unit, and after a standardized volume expansion with 500 mL of hetastarch 6%.
      MEASUREMENTS AND MAIN RESULTS: One-hundred thirty-five pairs of CO data were
      collected; the mean bias of all CO measurements corrected for repeated measures
      was 0.2 L/min with limits of agreements of -3.3 L/min and +2.9 L/min. The
      percentage error was 66.5%. The polar plot analysis included 71 significant ?CO
      and showed a mean polar angle of -3.4 degrees with 95% polar percentage error
      equivalent limits of -61 to 55; 69% of analysed data points fell within the 30
      degree limits and provided a correct polar concordance rate. CONCLUSIONS: Third
      generation FloTrac/Vigileo software still lacks the accuracy to reliably detect
      changes in cardiac output (?CO) in cardiac surgery. Improvements to
      FloTrac/Vigileo CO algorithm and software still are needed in this particular
      setting.

PMID- 24011912
TI  - Left ventricular "masses" in a patient with protein S deficiency and a recent
      myocardial infarction: evidence of intraventricular thrombi or a benign
      observation?

PMID- 24011913
TI  - [Treatments with immunoglobulin and thrombotic adverse events].
AB  - Treatments with intravenous or subcutaneous immunoglobulin (Ig) are used in a
      broad variety of disorders. Tolerance of Ig is usually good but adverse events,
      including some serious ones, have been reported and may differ among different Ig
      preparations. Thrombotic complications occur in 0.6 to 13% of cases and can
      involve arterial or venous circulation, rarely both. Deep venous thrombosis with
      or without pulmonary embolism, stroke or myocardial infarction remained the most
      frequent thrombotic complications. Some risk factors have been identified, mainly
      old age, multiple cardiovascular risk factors, and past history of thrombo
      embolic manifestations. Several mechanisms are suggested to explain this
      increased risk of thrombotic complications. Indeed, Ig treatments increase the
      plasma viscosity, increase and activate platelets, can trigger the coagulation
      cascade through the presence of activated factor XI in some Ig preparations, and
      release vasoactive molecules responsible for vasospasm. Patients have to be
      carefully monitored and risk factors to be identified as soon as possible. The
      role of antiplatelets or anticoagulation is not well determined but should
      probably be proposed to patients with high risk.

PMID- 24011914
TI  - Does mobile-bearing knee arthroplasty motion change with activity?
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of mobile
      bearing implant design and activity on knee arthroplasty kinematics during three
      activities of daily living. METHODS: In vivo kinematics were analyzed using 3D
      model registration from fluoroscopic images of non-weightbearing knee flexion
      extension, weight-bearing squatting and stair activities in 20 knees in 10
      patients with bilateral total knee arthroplasty. Each patient had one rotating
      platform and one meniscal-bearing variant of the same prosthesis design. RESULTS:
      Anteroposterior translations in meniscal-bearing knees were larger than those in
      rotating-platform knees for the different dynamic conditions. Meniscal-bearing
      knees showed more posterior femoral locations with activities that increased
      demand on the quadriceps. Condylar translations changed little in rotating
      platform knees with different activities. CONCLUSIONS: Activity dynamics can have
      a significant influence on knee kinematics, and have a greater effect on the
      kinematics of unconstrained meniscal-bearing prostheses than rotating-platform
      knee prostheses. LEVEL OF EVIDENCE: Level II.

PMID- 24011915
TI  - Fragmented QRS in patients with acute myocardial infarction.

PMID- 24011916
TI  - Therapeutic effects of p75 tumor necrosis factor receptor monoclonal antibody on
      a rat model of traumatic arthritis.
AB  - BACKGROUND: The aim of the present study was to investigate the therapeutic
      effects of p75 tumor necrosis factor receptor monoclonal antibody D8F2 on a
      traumatic arthritis model in rats, and to explore the underlying mechanism.
      METHODS: Forty male Sprague Dawley rats were randomly divided into five groups:
      (A) sham operation control group, (B) traumatic arthritis model group, (C) low
      dose D8F2 group (1 mg/kg), (D) medium-dose D8F2 group (3 mg/kg), and (E) high
      dose D8F2 group (10 mg/kg). Joint fluid samples were collected at 72 h after
      surgery, and enzyme-linked immunosorbent assay was performed to measure the
      following inflammatory factors: tumor necrosis factor alpha (TNF-alpha) and
      interleukin 1beta. One week after the surgery, rats were killed, and
      immunohistochemical staining was applied to detect the matrix metalloproteinase
      (MMP1 and MMP3) expression in the synovium. In cultured synovial fibroblast
      experiments, the D8F2-induced ubiquitination of TNF receptor-associated factor 2
      (TRAF2) was examined by immunoprecipitation, and nuclear translocation of p65
      nuclear factor-kappaB (p65NF-kappaB) mediated by TNF-alpha and D8F2 was analyzed
      by western blotting. RESULTS: In the traumatic arthritis model group, the
      inflammatory factors and MMPs were significantly increased relative to the sham
      operation control group (P < 0.05), whereas D8F2 could downregulate these factors
      in a dose-dependent manner (P < 0.05). The results from in vitro studies
      indicated that D8F2 can induce TRAF2 ubiquitination and inhibit the nuclear
      translocation of p65NF-kappaB mediated by TNF-alpha. CONCLUSIONS: p75 Tumor
      necrosis factor receptor monoclonal antibody has a therapeutic effect on
      traumatic arthritis, which may occur via the downregulation of inflammatory
      factors and MMPs at the transcription level because of TRAF2 degradation and
      inhibited activation of NF-kappaB.

PMID- 24011917
TI  - Early inactivation of PKCepsilon associates with late mitochondrial translocation
      of Bad and apoptosis in ventricle of septic rat.
AB  - BACKGROUND: Sepsis is usually accompanied by cardiomyocyte apoptosis and
      myocardial depression. Protein kinase C (PKC) has been reported to be important
      in regulating cardiac function and apoptosis; however, which PKC isoform is
      involved in sepsis-induced myocardial apoptosis remains unknown. MATERIALS AND
      METHODS: A rat model of sepsis by cecal ligation and puncture was used. Early and
      late sepsis refers to those rats sacrificed at 9 and 18 h after cecal ligation
      and puncture, respectively. Ventricular septum (Sep), left ventricle (LV), and
      right ventricle were fractionated into membrane, mitochondrial, and cytosolic
      fractions, individually. The protein levels of PKC isoforms (-alpha, -beta, 
      delta, -epsilon, -zeta, -iota, -lambda, and -MU) and mitochondrial translocation
      of Bad were quantified by Western blot analysis. Apoptosis was detected by
      terminal deoxynucleotidyl transferase-mediated dUTP in situ nick-end labeling.
      The morphology of mitochondria was examined by electron microscopy. RESULTS: The
      membrane/cytosol ratio of PKCepsilon was predominantly higher in the Sep, LV, and
      right ventricle under physiological conditions. At early sepsis, the
      membrane/cytosol ratio of PKCepsilon was significantly decreased in Sep and LV.
      At late sepsis, cardiomyocyte apoptosis associated with severe mitochondrial
      swelling and crista derangement were observed in Sep and LV at late sepsis.
      Additionally, mitochondria/cytosol ratio of Bad was significantly increased in
      Sep and LV. CONCLUSIONS: The early inactivation of PKCepsilon in the ventricle
      may affect the mitochondrial translocation of Bad and subsequent mitochondrial
      disruption and apoptosis at late sepsis. This finding opens up the prospect for a
      potential therapeutic strategy targeting PKCepsilon activation to prevent
      myocardial depression in septic patients.

PMID- 24011918
TI  - Low-dose aspirin therapy is not a reason for repeating head computed tomographic
      scans in traumatic brain injury: a prospective study.
AB  - BACKGROUND: Most studies have categorized all antiplatelet drugs into one
      category. The aim of our study was to evaluate the utility of repeat head
      computed tomography (RHCT) and outcomes in patients on low-dose aspirin
      (acetylsalicylic acid; ASA) therapy. METHODS: Patients with traumatic brain
      injury with intracranial hemorrhage on initial head computed tomography (CT) were
      prospectively enrolled. Patients on prehospital low-dose (81 mg) aspirin therapy
      were matched with patients exclusive of antiplatelet and anticoagulation therapy
      using propensity score matching in a 1:1 ratio for age, Glasgow Coma Scale, head
      Abbreviated Injury Scale score, Injury Severity Score, and neurological
      examination. Outcome measures were progression on RHCT and subsequent
      neurosurgical intervention. RESULTS: A total of 144 patients who had intracranial
      hemorrhage on initial CT scan (ASA group: 72; No-ASA group: 72) were enrolled.
      The mean age was 72.8 +/- 11.7 years, 59.7% were male, and median head
      Abbreviated Injury Scale was 3 (2-3). There was no difference in progression on
      RHCT (25% in ASA versus 16.6% in no-ASA), change in management as a result of
      RHCT (1.4% versus 1.4%), RHCT as a result of neurological decline (0 versus
      1.4%), discharge Glasgow Coma Scale (15 [14-15] versus 15 [14-15]), and mortality
      (0 versus 1.4%) between the two groups. CONCLUSIONS: Low-dose aspirin therapy is
      not associated with progression of initial insult on RHCT or clinical
      deterioration. Prehospital low-dose aspirin therapy as a sole criterion should
      not warrant a routine repeat head CT in traumatic brain injury.

PMID- 24011919
TI  - Involvement of peroxisome proliferator-activated receptor gamma in vitamin D
      mediated protection against acute kidney injury in rats.
AB  - BACKGROUND: Vitamin D has been reported as renoprotective agents in various
      studies. Recently, a few in vitro studies highlighted cross talk between vitamin
      D and peroxisome proliferator-activated receptor gamma (PPAR-gamma). The present
      study investigated the activation of PPAR-gamma as novel mechanism in vitamin D
      mediated protection against ischemia reperfusion-induced acute kidney injury
      (AKI) in rats. MATERIALS AND METHODS: The AKI was induced by clamping renal
      pedicles for 40 min followed by reperfusion for 24 h. The AKI was assessed by
      measuring creatinine clearance, serum urea, uric acid level, and lactate
      dehydrogenase activity. Moreover, serum potassium, calcium level, fractional
      excretion of sodium, and microproteinuria were measured in rats. The oxidative
      stress in renal tissues was assessed by quantification of thiobarbituric acid
      reactive substances, superoxide anion generation, reduced glutathione level, and
      catalase and myeloperoxidase activities. The hematoxylin-eosin staining was
      carried out to observe histopathologic changes in renal tissues. Vitamin D (0.25,
      0.5, and 1 MUg/kg) was administered for 7 d before subjecting rats to renal
      ischemia reperfusion injury (IRI). RESULTS: The renal IRI in rats induced
      significant changes in serum, urinary, and oxidative stress parameters in renal
      tissues. Moreover, hematoxylin-eosin staining revealed marked damage produced by
      IRI in renal tissues. The administration of vitamin D at 0.5 MUg/kg dose afforded
      maximum protection against renal IRI. The prior treatment with PPAR-gamma
      antagonist bisphenol A diglycidyl ether significantly attenuated protective
      effect of vitamin D, thus confirming involvement of PPAR-gamma in vitamin D
      mediated renoprotection. CONCLUSIONS: It is concluded that activation of PPAR
      gamma significantly contributes toward vitamin D-mediated protection against
      ischemia reperfusion-induced AKI.

PMID- 24011920
TI  - Does an aberrant right hepatic artery really influence the short- and long-term
      results of a pancreaticoduodenectomy for malignant disease? A matched case
      controlled study.
AB  - BACKGROUND: An aberrant right hepatic artery (ARHA) is a common anatomic
      variation. The risk associated with ARHA during pancreaticoduodenectomy (PD)
      continues to be debated. The aim of this study was to compare the clinical
      outcomes and survival after PD with ARHA against a matched cohort of patients
      without ARHA. METHODS: PD with an ARHA performed between January 2000 and
      September 2009 were retrospectively analyzed. Patients with an ARHA (group 1)
      were matched (1:2) to patients without an ARHA (group 2) according to gender,
      age, body mass index, type of tumor, and lymph node status. Peri- and
      postoperative outcomes were compared between the two groups. Overall survival and
      disease-free survival were estimated by Kaplan-Meier method and compared with log
      rank test. RESULTS: A total of 29 patients (group 1) and 55 patients (group 2)
      were compared. In group 1, an ARHA entered the tumor in six cases (20.7%), was
      sacrificed in four cases, and repaired in two cases. There was no difference
      regarding the rate of intraoperative and postoperative variables between the two
      groups. The oncological clearance (P = 0.731) and survival (overall survival, P =
      0.843; disease-free survival, P = 0.832) were also similar. CONCLUSIONS: Our
      study showed that the presence of an ARHA during PD was not associated with worse
      postoperative outcomes or survival.

PMID- 24011921
TI  - Neuroprotective effect of tadalafil, a PDE-5 inhibitor, and its modulation by L
      NAME in mouse model of ischemia-reperfusion injury.
AB  - BACKGROUND: The present study investigates the neuroprotective effect of
      tadalafil, a selective phosphodiesterase-5 inhibitor, in a mouse model of
      ischemia-reperfusion injury. MATERIALS AND METHODS: Bilateral carotid artery
      occlusion for 12 min followed by reperfusion for 24 h was employed to produce
      ischemia-reperfusion-induced cerebral injury in male Swiss mice. Cerebral infarct
      size was measured using triphenyltetrazolium chloride staining. Memory was
      assessed using Morris water maze test. Degree of motor incoordination was
      evaluated using inclined beam walk test, rota-rod test, and lateral push test.
      Brain nitrite/nitrate, brain acetylcholinesterase activity, brain thiobarbituric
      acid reactive species, and glutathione levels were also estimated. RESULTS:
      Bilateral carotid artery occlusion, followed by reperfusion, produced a
      significant rise in cerebral infarct size, brain nitrite/nitrate levels,
      acetylcholinesterase activity, and thiobarbituric acid reactive species level
      along with a fall in glutathione. A significant impairment of memory and motor
      coordination was also noted. Pretreatment of tadalafil significantly attenuated
      the above effects of ischemia-reperfusion injury. Tadalafil-induced
      neuroprotective effects were significantly attenuated by administration of L
      NAME, a nonselective nitric oxide synthase inhibitor. CONCLUSIONS: Results
      indicate that tadalafil exerts neuroprotective effects, probably through nitric
      oxide-dependent pathways. Therefore, phosphodiesterase-5 can be explored as an
      important target to contain ischemia-reperfusion injury.

PMID- 24011922
TI  - (Pro)renin receptor blocker improves survival of rats with sepsis.
AB  - BACKGROUND: The renin-angiotensin system (RAS) affects inflammatory responses
      during sepsis. Nonproteolytic activation of prorenin by the (pro)renin receptor
      has recently been shown to stimulate the tissue RAS. In the present study, the
      effect of (pro)renin receptor blocker (PRRB) pretreatment on sepsis in a rat
      cecal ligation and puncture (CLP) model was investigated. MATERIALS AND METHODS:
      Male Sprague-Dawley rats underwent CLP and were randomly divided into two groups:
      PRRB-treated group and control peptide-treated group. Survival was analyzed for 7
      d after CLP. The serum concentrations of cytokines and high-mobility group box
      chromosomal protein 1 (HMGB1) were measured at three time points (0, 3, and 6 h
      after CLP). Hematoxylin-eosin staining and immunohistochemical staining for
      nonproteolytically activated prorenin and HMGB1 were performed on the cecum to
      assess pathologic changes found 6 h after CLP. RESULTS: Treatment with PRRB
      improved the survival rate of the post-CLP septic rats (P = 0.023). PRRB also
      significantly reduced serum tumor necrosis factor-alpha, interleukin-1beta, and
      HMGB1 levels 6 h after CLP. In CLP rats that were treated with control peptide,
      the expression of activated prorenin was elevated in peritoneal foam cells.
      Moreover, expression of HMGB1 was increased in peritoneal inflammatory cells. In
      contrast, both were markedly suppressed in CLP rats that were treated with PRRB.
      CONCLUSIONS: PRRB significantly improved the survival rate of rats with
      clinically relevant sepsis, possibly by attenuating a sepsis-induced systemic
      inflammatory response. We propose that overactivation of the RAS by activation of
      prorenin in foam cells may be a significant contributor to sepsis.

PMID- 24011923
TI  - Death certification practice in Qatar.
AB  - OBJECTIVE: To evaluate the knowledge and practice of death certification among
      physicians in Qatar. STUDY DESIGN: Cross-sectional study. METHODS: Knowledge and
      practice of death certification were assessed in a group of 317 physicians,
      selected at random, using a self-administered questionnaire. RESULTS: Only 22.7%
      of physicians had received formal training in death certification. More than 60%
      of physicians knew which healthcare workers were entitled to complete the cause
      of death section of the form, and 37% of physicians were aware of the conditions
      for referral to a forensic physician. The most common difficulties facing
      physicians, when completing death certification forms, were dealing with
      complicated cases (47.3%), lack of training (43.5%) and failure to understand the
      terms used in the form (39.6%). Only 21.5% of physicians identified the cause of
      death correctly in the case scenario; 53.2% of physicians made major errors and
      62.8% made minor errors. CONCLUSION: Lack of training appears to play a major
      role in the poor completion of death certification forms.
      Educational/administrative interventions and training activities are needed.

PMID- 24011924
TI  - High glucose-induced proteome alterations in hepatocytes and its possible
      relevance to diabetic liver disease.
AB  - Hyperglycemia can cause several abnormalities in liver cells, including diabetic
      liver disease. Previous research has shown that high blood glucose levels can
      damage liver cells through glycoxidation. However, the detailed molecular
      mechanisms underlying the effects of high blood glucose on the development of
      diabetic liver disease have yet to be elucidated. In this study, we cultured a
      liver cell line (Chang liver cell) in mannitol-balanced 5.5 mM, 25 mM and 100 mM
      d-glucose media and evaluated protein expression and redox regulation. We
      identified 141 proteins that showed significant changes in protein expression and
      29 proteins that showed significant changes in thiol reactivity, in response to
      high glucose concentration. Several proteins involved in transcription-control,
      signal transduction, redox regulation and cytoskeleton regulation showed
      significant changes in expression, whereas proteins involved in protein folding
      and gene regulation displayed changes in thiol reactivity. Further analyses of
      clinical plasma specimens confirmed that the proteins AKAP8L, galectin-3, PGK 1,
      syntenin-1, Abin 2, aldose reductase, CD63, GRP-78, GST-pi, RXR-gamma, TPI and
      vimentin showed type 2 diabetic liver disease-dependent alterations. In summary,
      in this study we used a comprehensive hepatocyte-based proteomic approach to
      identify changes in protein expression and to identify redox-associated diabetic
      liver disease markers induced by high glucose concentration. Some of the
      identified proteins were validated with clinical samples and are presented as
      potential targets for the prognosis and diagnosis of diabetic liver disease. 

PMID- 24011925
TI  - Prevalence and determinants of elevated high-sensitivity cardiac troponin T in
      hypertrophic cardiomyopathy.
AB  - BACKGROUND: This study was designed to evaluate the prevalence and determinants
      of increased high-sensitivity cardiac troponin T (hs-cTnT) as a marker of cardiac
      injury in patients with hypertrophic cardiomyopathy (HCM). METHODS: A total of 98
      consecutive patients with HCM (71.4% males; mean age 51.18 +/- 15.47 years)
      between 2012 and 2013 were evaluated by measuring the level of serum hs-cTnT
      along with other clinical assessments. RESULTS: There were 42 (42.9%) patients
      with a minimum serum hs-cTnT level of 14 ng/L. The mean hs-cTnT level was 12.37
      ng/L (6.94-24.26 ng/L). There were significant differences in chest pain New York
      Heart Association functional class, left ventricular hypertrophy in the surface
      electrocardiogram, non-sustained ventricular tachycardia in 24-h
      electrocardiogram-Holter monitoring, left atrial (LA) area index, ratio of peak
      early (E) transmitral filling velocity to peak early diastolic annular velocity
      (Ea septal) at the level of the septal mitral annulus (E/Ea septal), maximum left
      ventricular (LV) wall thickness >= 30 mm, and peak LV outflow gradient >= 30 mmHg
      in echocardiography between the patients with hs-cTnT<14 ng/L and those with hs
      cTnT >= 14 ng/L. However, after multivariate analysis, age, maximum LV wall
      thickness, LA area index, and E/Ea septal remained as the independent
      determinants of elevated hs-cTnT in HCM. CONCLUSIONS: The results demonstrated
      that hs-cTnT was elevated in a significant number of our HCM patients; therefore,
      hs-cTnT can be introduced as a valuable marker of myocardial injury in HCM
      patients.

PMID- 24011926
TI  - Impact of admission glycemia and glycosylated hemoglobin A1c on long-term
      clinical outcomes of non-diabetic patients with acute coronary syndrome.
AB  - BACKGROUND: Admission glucose levels have proven to be a predictor in patients
      with acute myocardial infarction and elevated glycosylated hemoglobin A1c (HbA1c)
      is associated with an increased risk of cardiovascular disease, even in patients
      without diabetes. However, the effect of both admission glucose and HbA1c levels
      on clinical outcomes in non-diabetic patients with acute coronary syndrome (ACS)
      has not been fully elucidated. We evaluated the combined effect of admission
      glucose and HbA1c values on long-term clinical outcomes in non-diabetic patients
      with ACS treated with percutaneous coronary intervention (PCI). METHODS AND
      RESULTS: This was an observational study of 452 consecutive non-diabetic patients
      with ACS who underwent PCI between January 1997 and December 2006. The patients
      were assigned to four groups according to the median values of admission glucose
      and HbA1c. The primary endpoint comprising a composite of all-cause death and non
      fatal MI was compared among the four groups. The primary endpoint occurred in
      13.3% of the participants during a median follow-up period of 4.7 years. The
      cumulative incidence rate of primary endpoint significantly differed among the
      groups (p=0.048). Multivariable Cox regression analysis showed that the
      combination of elevated admission glucose and HbA1c was independently associated
      with long-term clinical outcomes. CONCLUSIONS: Combined admission glucose and
      HbA1c values were independently associated with clinical outcomes in non-diabetic
      patients with ACS treated with PCI.

PMID- 24011927
TI  - The effect of medial release of the distal patellar tendon insertion on lateral
      patella translation and residual insertion strength: a cadaveric study.
AB  - Patellar tendon avulsion is a risk with difficult exposure in a stiff knee,
      patella baja or previous tibial osteotomy. We sought to define a safe amount of
      release of the patellar tendon insertion for such cases. Eleven pairs of fresh
      frozen cadaveric lower limb specimens were acquired and randomized to either
      intact or partial release of the distal tibial insertion. Partial release of the
      tibial insertion of the tendon increased lateral exposure a mean 29% +/- 15% (P =
      0.002) while reducing ultimate strength to a mean of 80% that of the intact
      contralateral tendon. Measured patella release increased lateral patella
      translation and can be performed without risk of catastrophic rupture with basic
      activities of daily living following TKA.

PMID- 24011928
TI  - Alzheimer's disease in the human eye. Clinical tests that identify ocular and
      visual information processing deficit as biomarkers.
AB  - Alzheimer's disease (AD) is the most common form of dementia with progressive
      deterioration of memory and cognition. Complaints related to vision are common
      among AD patients. Several changes in the retina, lens, and in the vasculature
      have been noted in the AD eye that may be the cause of visual symptoms
      experienced by the AD patient. Anatomical changes have been detected within the
      eye before signs of cognitive impairment and memory loss are apparent. Unlike the
      brain, the eye is a unique organ that can be visualized noninvasively at the
      cellular level because of its transparent nature, which allows for inexpensive
      testing of biomarkers in a clinical setting. In this review, we have searched for
      candidate biomarkers that could enable diagnosis of AD, covering ocular
      neurodegeneration associated with functional tests. We explore the evidence that
      suggests that inexpensive, noninvasive clinical tests could be used to detect AD
      ocular biomarkers. 

PMID- 24011929
TI  - Cytotoxic behavior and spectroscopic characterization of metal complexes of
      ethylacetoacetate bis(thiosemicarbazone) ligand.
AB  - Reaction of Cr(III), Mn(II), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) ion with
      2,4-dihydrazino-thioamido-1-ethoxybutane led to the formation of mono and
      binuclear complexes. These complexes have been characterized by elemental
      analyses, IR, UV-Vis spectra, magnetic moments, molar conductances, (1)H NMR and
      mass spectra (ligand and its Zn(II) complex), thermal analyses (DTA and TGA) and
      ESR measurements. The IR data suggest the involvement of sulfur and azomethane
      nitrogen atoms in coordination to the central metal ion .The Molar conductances
      of the complexes in DMF are commensurate with their non-ionic character. The ESR
      spectra of Cu(II) complexes show axial type symmetry (d(x2-y2)) ground state with
      covalent bond character. On the basis of spectral studies, octahedral or
      tetrahedral geometry has been assigned to the metal complexes. Complexes have
      been tested invitro against tumor cells and number of microorganisms in order to
      assess their antitumor and antimicrobial properties.

PMID- 24011930
TI  - Microcalorimetric investigation of the effect of non-ionic surfactant on
      biodegradation of pyrene by PAH-degrading bacteria Burkholderia cepacia.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widespread in various ecosystems and
      are pollutants of great concern due to their potential toxicity, mutagenecity and
      carcinogenicity. Surfactant has become a hot topic for its wide application in
      the bioremediation of PAHs. The aim of this work is to explore a
      microcalorimetric method to determine the toxic effect of pyrene on Bacillus
      subtilis (B. subtilis) and the PAH-degrading bacteria Burkholderia cepacia (B.
      cepacia) and to evaluate the effect of Tween 80 on biodegradation of pyrene.
      Power-time curves were studied and calorimetric parameters including the growth
      rate constant (k), half inhibitory concentration (IC50), and total thermal effect
      (Q(T)) were determined. B. subtilis, B. cepacia and B. cepacia with Tween 80 were
      completely inhibited when the concentration of pyrene were 200, 800 and 1600 ug
      mL-1, respectively. B. cepacia shows better tolerance to pyrene than B. subtilis.
      Tween 80 significantly improves the biodegradation of pyrene by increasing the
      bioavailability of pyrene. In addition, the expression of catechol 2,3
      dioxygenase (C23O) in B. cepacia is responsible for the degradation of pyrene and
      plays an important role in improving the biodegradation of pyrene. Moreover, the
      activity of C23O increases with the application of Tween 80. The enhanced
      bioavailability and biodegradation of pyrene by Tween 80 shows the potential use
      of Tween 80 in the PAHs bioremediation.

PMID- 24011931
TI  - Increase in lens capsule stiffness caused by vital dyes.
AB  - PURPOSE: To assess potential changes in lens capsule mechanical properties after
      staining with brilliant blue, indocyanine green (ICG), and trypan blue. SETTING:
      Department of Ophthalmology and Applied Physics and Center for NanoScience,
      Ludwig-Maximilians-University, Munich, Germany. DESIGN: Experimental study.
      METHODS: Fifteen unstained lens capsules were dissected into 7 wedge-shaped
      parts. Three fragments were stained with brilliant blue 0.025%, ICG 0.05%, and
      trypan blue 0.06%, respectively, for 1 minute. Another 3 specimens were
      additionally illuminated using a standard light source. The seventh part served
      as an untreated control. All specimens were analyzed using atomic force
      microscopy (AFM) in contact mode with a scan rate of 0.6 Hz. Two scan regions of
      10 MUm * 10 MUm were chosen, and stiffness was determined using AFM in a force
      spectroscopy mode. The force curves were performed with a data rate of 5000 Hz.
      RESULTS: Staining of the samples resulted in an increase in tissue stiffness
      (brilliant blue: P<.001; ICG: P<.01; trypan blue: P<.05). Additional illumination
      after staining further increased tissue stiffness, but not significantly. Mean
      increase in the relative elasticity values were 1.61 +/- 0.15 (SD) for brilliant
      blue, 2.04 +/- 0.21 for brilliant blue with illumination, 1.63 +/- 0.22 for ICG,
      2.01 +/- 0.22 for ICG with illumination, 1.23 +/- 0.11 for trypan blue, and 1.39
      +/- 0.11 for trypan blue with illumination. In relation to unstained tissue, the
      relative elasticity of the stained tissue increased 1.2-fold after illumination.
      CONCLUSION: Staining significantly increased the mechanical properties of the
      human lens capsule. FINANCIAL DISCLOSURE: No author has a financial or
      proprietary interest in any material or method mentioned.

PMID- 24011932
TI  - Femtosecond laser-assisted intrastromal corneal ring segment implantation for
      high astigmatism correction after penetrating keratoplasty.
AB  - PURPOSE: To assess the visual and refractive outcomes of femtosecond laser
      assisted implantation of Ferrara-type intrastromal corneal ring segments (ICRS)
      in post-penetrating keratoplasty (PKP) eyes. SETTING: Instituto Oftalmologico
      Fernandez-Vega, Oviedo, Spain. DESIGN: Cohort study. METHODS: Patients with
      previous PKP had ICRS implantation after femtosecond laser tunnel creation. The
      uncorrected (UDVA) and corrected (CDVA) distance visual acuities and residual
      refractive errors were recorded before and 6 months after ICRS implantation. The
      power vector method was used to analyze refractive errors preoperatively and
      postoperatively. RESULTS: This study enrolled 32 eyes of 30 patients. The mean
      UDVA (Snellen decimal) changed from 0.16 +/- 0.15 (SD) preoperatively to 0.43 +/-
      0.28 postoperatively (P<.0001). Postoperatively, the UDVA was 20/40 or better in
      40.6% of eyes. The mean CDVA was 0.67 +/- 0.22 preoperatively and 0.80 +/- 0.19
      postoperatively (P<.0001). Postoperatively, the CDVA was better than 20/40 in
      96.9% of eyes and 20/25 or better in 56.2% of eyes. By 6 months postoperatively,
      no eye had lost more than 2 lines of CDVA, 4 eyes lost 1 line, 6 eyes had no
      change, 9 eyes gained 1 line, and 13 eyes gained 2 or more lines. The safety
      index at 6 months was 1.20. The spherical equivalent and astigmatism components
      were significantly reduced after ICRS implantation (P<.04). CONCLUSION:
      Intrastromal corneal ring segment implantation using the femtosecond laser may be
      a good alternative for high astigmatism correction in post-PKP eyes.

PMID- 24011933
TI  - High fasting blood glucose and obesity significantly and independently increase
      risk of breast cancer death in hormone receptor-positive disease.
AB  - PURPOSE: We investigated the effect of fasting blood glucose and body mass index
      (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five
      Italian cancer registries in 2003-2005 and followed up to the end of 2008.
      METHODS: For 1607 Italian women (>=15 years) with information on BMI or blood
      glucose or diabetes, we analysed the risk of breast cancer death in relation to
      glucose tertiles (<=84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified
      categories; BMI tertiles (<=23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage
      (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and
      progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age,
      chemotherapy and endocrine therapy, using multiple regression models. Separate
      models for ER+PR+ and ER-PR- cases were also run. RESULTS: Patients often had T1
      3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6%
      were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI
      (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with
      adjustment for other variables, breast cancer mortality was higher in women with
      high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95%
      confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in
      women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1
      94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). CONCLUSION: Our results provide evidence that
      in ER+PR+ patients, high blood glucose and high BMI are independently associated
      with increased risk of breast cancer death. Detection and correction of these
      factors in such patients may improve prognosis.

PMID- 24011934
TI  - Synergistic inhibition of ovarian cancer cell growth by combining selective
      PI3K/mTOR and RAS/ERK pathway inhibitors.
AB  - BACKGROUND: Ovarian cancer is the major cause of death from gynaecological
      malignancy with a 5year survival of only ~30% due to resistance to platinum and
      paclitaxel-based first line therapy. Dysregulation of the phosphoinositide 3
      kinase/mammalian target of rapamycin (PI3K/mTOR) and RAS/extracellular signal
      regulated kinase (ERK) pathways is common in ovarian cancer, providing potential
      new targets for 2nd line therapy. METHODS: We determined the inhibition of
      proliferation of an extensive panel of ovarian cancer cell lines, encompassing
      all the major histotypes, by the dual PI3K/mTOR inhibitor PF-04691502 and a MEK
      inhibitor, PD-0325901. In addition, we analysed global gene expression, mutation
      status of key PI3K/mTOR and RAS/ERK pathway members and pathway activation to
      identify predictors of drug response. RESULTS: PF-04691502 inhibits proliferation
      of the majority of cell lines with potencies that correlate with the extent of
      pathway inhibition. Resistant cell lines were characterised by activation of the
      RAS/ERK pathway as indicated by differential gene expression profiles and pathway
      activity analysis. PD-0325901 suppressed growth of a subset of cell lines that
      were characterised by high basal RAS/ERK signalling. Strikingly, using PF
      04691502 and PD-0325901 in combination resulted in synergistic growth inhibition
      in 5/6 of PF-04691502 resistant cell lines and two cell lines resistant to both
      single agents showed robust synergistic growth arrest. Xenograft studies confirm
      the utility of combination therapy to synergistically inhibit tumour growth of PF
      04691502-resistant tumours in vivo. CONCLUSIONS: These studies identify dual
      targeted inhibitors of PI3K/mTOR in combination with inhibitors of RAS/ERK
      signalling as a potentially effective new approach to treating ovarian cancer.

PMID- 24011935
TI  - Population-based incidence, treatment and survival of patients with peritoneal
      metastases of unknown origin.
AB  - AIM: Until recently, peritoneal metastases (PM) were regarded as an untreatable
      condition, regardless of the organ of origin. Currently, promising treatment
      options are available for selected patients with PM from colorectal, appendiceal,
      ovarian or gastric carcinoma. The aim of this study was to investigate the
      incidence, treatment and survival of patients presenting with PM in whom the
      origin of PM remains unknown. METHODS: Data from patients diagnosed with PM of
      unknown origin during 1984-2010 were extracted from the Eindhoven Cancer
      Registry. European age-standardised incidence rates were calculated and data on
      treatment and survival were analysed. RESULTS: In total 1051 patients were
      diagnosed with PM of unknown origin. In 606 patients (58%) the peritoneum was the
      only site of metastasis, and 445 patients also had other metastases. Chemotherapy
      usage has increased from 8% in the earliest period to 16% in most recent years
      (p=.016). Median survival was extremely poor with only 42days (95% confidence
      interval (CI) 39-47days) and did not change over time. Median survival of
      patients not receiving chemotherapy was significantly worse than of those
      receiving chemotherapy (36 versus 218days, p<.0001). CONCLUSION: The prognosis of
      PM of unknown origin is extremely poor and did not improve over time. Given the
      recent progress that has been achieved in selected patients presenting with PM,
      maximum efforts should be undertaken in order to diagnose the origin of PM as
      accurately as possible. Potentially effective treatment strategies should be
      further explored for patients in whom the organ of origin remains unknown.

PMID- 24011936
TI  - Trends in incidence and survival of Dutch women with vulvar squamous cell
      carcinoma.
AB  - AIM: Previous studies showed an increase in incidence of vulvar intraepithelial
      neoplasia (VIN), the premalignant lesion of Vulvar Squamous Cell Carcinoma
      (VSCC). Furthermore, during the last decades treatment of VSCC became less
      radical. Considering these changes the aim of this study was to describe trends
      of incidence and survival of patients with VSCC in the Netherlands. METHODS: All
      patients with VSCC diagnosed between 1989 and 2010 (n=4614) were selected from
      the Netherlands Cancer Registry. Trends in age-adjusted incidence rates were
      evaluated by calculating the estimated annual percentage change (EAPC). Joinpoint
      regression analysis was used to detect changes in trends. Five-year relative
      survival rates were calculated for four time periods. RESULTS: The incidence of
      VSCC has increased since 2002 (EAPC 5.0; 95% confidence interval (CI): 2.7-7.7%).
      In women aged <60years incidence rates increased significantly during the whole
      study period (EAPC 3.5%; 95% CI: 2.0-4.9), while in women aged >= 60 years only
      an increase has observed from 2004 onwards (EAPC 5.0; 95% CI: 1.5-8.6). Survival
      rates did not change over time. CONCLUSION: The incidence rate of VSCC has
      increased from 2002 onwards in all women. Over the whole study period the
      increase was strongest in women aged <60 years. The introduction of less radical
      surgery did not affect survival.

PMID- 24011937
TI  - Platinum-sensitivity in metastatic colorectal cancer: towards a definition.
AB  - BACKGROUND: First-line oxaliplatin-based therapy is the standard treatment of
      metastatic colorectal cancer (mCRC), but its dose-limiting toxicity is sensory
      neuropathy. The OPTIMisation of OXaliplatin (OPTIMOX) stop-and-go approach with
      oxaliplatin-free interval (OFI) offers a reasonable strategy. Influence of the
      first-line oxaliplatin-based treatment efficacy and the duration of OFI on tumour
      sensitivity to oxaliplatin reintroduction were investigated. METHODS: This was a
      pooled analysis of OPTIMOX1 and OPTIMOX2 studies, on 285 patients with previously
      untreated mCRC and FOLFOX reintroduction. An optimal OFI was estimated. Efficacy
      endpoints measured from reintroduction of FOLFOX included response rate (RR),
      progression-free survival (PFS) and overall survival (OS). FINDINGS: Two groups
      of OFI <6 and >= 6 months, were defined. The RR following FOLFOX reintroduction
      were 14% and 22% in patients with an OFI <6 and >= 6 months, respectively
      (overall RR 19%). The median PFS after FOLFOX reintroduction following OFI< 6 and
      >= 6 months were 3.0 [95% confidence intervals (CI): 2.7-3.7] and 5.5 months [95%
      CI: 4.8-6.5], respectively. The median OS following OFI <6 months was 8.8 months
      [95% CI: 7.5-10.5] and OFI >= 6 was months 16.8 months [95% CI: 15.3-19.6]. In
      the case of partial response (PR), median PFS and OS were 4.6 [95% CI: 4.1-5.0]
      and 14 months [95% CI: 12.1-16.4], respectively, whereas in patients with initial
      stable disease (SD) 3.4 [95% CI: 2.7-4.7] and 10.3 months [95% CI: 7.3-12.9],
      respectively. INTERPRETATION: A sensitive population of patients more likely to
      benefit from oxaliplatin reintroduction is defined by the efficacy of induction
      therapy followed by an OFI of at least 6 months between two periods of FOLFOX
      therapy. OFI of < 6 months identifies a subgroup of partially-resistant patients
      who can still benefit from oxaliplatin reintroduction.

PMID- 24011938
TI  - Clinical evaluation of pepsin for laryngopharyngeal reflux in children with
      otitis media with effusion.
AB  - OBJECTIVE: We sought to evaluate the clinical role of pepsin for
      laryngopharyngeal reflux (LPR) in children with otitis media with effusion (OME).
      METHODS: Pepsin/pepsinogen and fibrinogen were analyzed in fifty effusion and
      blood samples of children with OME using enzyme linked immunosorbent assay
      (ELISA). Ambulatory 24-h dual-probe pH monitoring was additionally performed in
      31 children divided into two groups according to response of medical treatment.
      RESULTS: The effusion levels of pepsin/pepsinogen ranged from 8.5 to 1512 MUg/dl
      and were up to 4-540 times higher than the concentrations found in plasma
      samples. The effusion levels of fibrinogen ranged from 0.05 to 4.1g/dl. Some
      effusion samples showed fibrinogen concentrations did not exceed 10 times higher
      than the concentrations found in plasma samples and others showed lower
      concentrations. The pH of effusion samples was 7.13 to 8.72. Dual-probe pH
      monitoring showed that 22/31 (71%) of the studied children had significant acid
      reflux documented by either the esophageal probe or the pharyngeal probe and all
      of them had LPR. There is a significant positive correlation between the level of
      pepsin assayed in the effusions and the number of pharyngeal reflux episodes
      measured by pH monitoring. CONCLUSIONS: Analysis of pepsin/pepsinogen in effusion
      samples of children with OME, using ELISA, can be considered as a reliable
      biochemical marker for assessment of laryngopharyngeal reflux.

PMID- 24011939
TI  - Psychiatric disorders and symptoms severity in patients with adenotonsillar
      hypertrophy before and after adenotonsillectomy.
AB  - OBJECTIVE: The objective of this study was to compare the frequency of
      psychiatric disorders and the severity of psychiatric symptoms in patients with
      adenotonsillar hypertrophy with a healthy control group and investigate the
      potential improvement after adenotonsillectomy. MATERIALS AND METHODS: The study
      group consisted of 40 patients with adenotonsillar hypertrophy and a control
      group consisted of 35 healthy volunteers without adenotonsillar hypertrophy. A
      routine ear nose throat (ENT) examination, flexible nasopharyngoscopy and
      tympanometry were carried out. The same procedures were applied to the control
      group. The parents of all the participants were required to fill out the Early
      Childhood Inventory-4 form, the Strengths and Difficulties Questionnaire and a
      personal information form. At postoperative month six, the patients were re
      examined, and their parents were required to fill out the same forms. RESULTS:
      Attention deficit hyperactivity disorders and sleep disorders determined with the
      Early Childhood Inventory-4 were more common in the patients with adenotonsillar
      hypertrophy than in the control group. There was a significant decrease in the
      rates of both types of disorders at postoperative month six. The total
      psychiatric symptom severity was higher in the patients with adenotonsillar
      hypertrophy and the following were more frequent: cases of attention deficit
      hyperactivity disorder, oppositional defiant disorder, symptom severity of
      anxiety disorders and sleep disorders determined with the Early Childhood
      Inventory-4, as well as emotional problems, attention deficit hyperactivity
      disorder problems, behavioural problems and peer problems determined with the
      Strengths and Difficulties Questionnaire parent-report form. There was a
      statistically significant decrease in all the other symptoms at postoperative
      month six, except for the severity of oppositional defiant disorder symptoms
      determined with the Early Childhood Inventory-4 and behavioural problems
      determined with the Strengths and Difficulties Questionnaire parent-report form.
      There were no differences in the severity of psychiatric disorders or symptoms
      between the adenotonsillar hypertrophy group and the control group at
      postoperative month six. CONCLUSION: Adenotonsillar hypertrophy is associated
      with psychiatric disorders and symptoms. Adenotonsillectomy ameliorated the
      symptoms and the severity of these disorders in most cases.

PMID- 24011940
TI  - Septicaemic pasteurellosis in free-range pigs associated with an unusual biovar
      13 of Pasteurella multocida.
AB  - Biochemical profiles, PFGE typing and MLST analysis were used to investigate an
      outbreak of septicaemic pasteurellosis in a free-range pig farm in Spain. Signs
      of coughing, dyspnoea and a visible inflammation of the ventral area of the neck
      (jowl), which acquired a cyanotic and necrotic appearance, were the
      characteristic findings in affected animals, associated with a high morbidity
      (70%) and case mortality (95%). Diffuse, haemorrhagic and fibrinous
      pleuroneumonia and acute, focally extensive and haemorrhagic myositis and
      panniculitis were observed in the histopathological analysis from three analyzed
      animals. Pasteurella multocida subsp. multocida, capsular type B, biovar 13 was
      isolated in pure culture from lung, submandibular tissue (jowl), liver, spleen
      and kidney tissue from diseased pigs. After PFGE typing, all P. multocida
      isolates displayed undistinguishable macrorestriction patterns with Bsp120I
      restriction enzyme demonstrating that the infection was caused by a single
      strain. With the multihost P. multocida MLST database, all P. multocida isolates
      were assigned to the new sequence type ST47 which was highly related with other
      bovine isolates of P. multocida type B associated with haemorrhagic septicaemia.
      This is the first description of an outbreak of septicaemic pasteurellosis in
      free-range pigs associated with P. multocida type B of the unusual biovar 13. The
      communication and complete diagnosis of cases of swine septicaemia and the
      possible role of pigs as reservoirs of this new pathogen must be evaluated to
      determine the importance of this disease for pigs. 

PMID- 24011941
TI  - Hormonal manipulations in the 5-day timed artificial insemination protocol to
      optimize estrous cycle synchrony and fertility in dairy heifers.
AB  - Objectives were to determine the effects of GnRH at the initiation of the 5-d
      timed artificial insemination (AI) program combined with 2 injections of
      PGF2alpha on ovarian responses and pregnancy per AI (P/AI) in dairy heifers, and
      the role of progesterone concentrations on LH release and ovulation in response
      to GnRH. In study 1, heifers received a controlled internal drug release (CIDR)
      insert containing 1.38 g of progesterone on d 0, an injection of 25 mg of
      PGF2alpha and CIDR removal on d 5, and an injection of 100 MUg GnRH concurrently
      with AI on d 8. Heifers were assigned to receive no additional treatment
      (control; n=559) or an injection of GnRH on d 0 and a second injection of
      PGF2alpha on d 6 (G2P; n=547). In study 2, all heifers were treated as described
      for the control in study 1, and were allocated to receive no additional treatment
      (control; n=723), an injection of PGF2alpha on d 6 (NG2P; n=703), or an injection
      of GnRH on d 0 and an injection of PGF2alpha on d 6 (G2P; n=718). In study 3,
      heifers received a CIDR on d 7 after ovulation and were assigned randomly to a
      low-progesterone (LP; n=6) treatment in which 2 injections of 25 mg of PGF2alpha
      each were administered 12h apart, on d 7 and 7.5 after ovulation, or to a high
      progesterone (HP; n=12) treatment in which no PGF2alpha was administered. On d 8,
      heifers received 100 MUg of GnRH and blood was sampled at every 15 min from -30
      to 180 min relative to the GnRH for assessment of LH concentrations.
      Additionally, 94 heifers were assigned to LP or HP and ovulation in response to
      GnRH was evaluated. In study 1, P/AI was greater for G2P than for the control on
      d 32 (59.4 vs. 53.5%) and 60 after AI (56.6 vs. 51.3%). In study 2,
      administration of GnRH on d 0 increased the proportion of heifers with a new
      corpus luteum on d 5 (control=21.9 vs. NG2P=20.1 vs. G2P=34.4%). Administration
      of a second PGF2alpha increased the proportion of heifers with progesterone <0.5
      ng/mL at AI (control=83.1 vs. NG2P=93.0 and G2P=87.2%). Pregnancy per AI was
      greater for G2P than for control and NG2P on d 32 (control=52.9 vs. NG2P=55.0 vs.
      G2P=61.7%) and 60 (control=49.0 vs. NG2P=51.6 vs. G2P=59.1%). In study 3, HP
      attenuated LH release and reduced ovulation (19.0 vs. 48.4%) in response to GnRH
      compared with LP. Combining GnRH and 2 doses of PGF2alpha in the 5-d timed AI
      protocol improved follicle turnover, luteolysis, and P/AI in heifers. Elevated
      concentrations of progesterone suppressed LH release and are linked with the low
      ovulatory response to the initial GnRH treatment of the protocol.

PMID- 24011942
TI  - Effect of beta-lactoglobulin A and B whey protein variants on cheese yield
      potential of a model milk system.
AB  - Cheese yield mainly depends on the amount and proportion of milk constituents;
      however, genetic variants of the proteins present in milk may also have an
      important effect. The objective of this research was to study the effect of the
      variants A and B of beta-lactoglobulin (LG) on cheese yield using a model system
      consisting of skim milk powder fortified with different levels of a mixture
      containing alpha-lactalbumin and beta-LG genetic variants (A, B, or A-B) in a 1:2
      ratio. Fortified milk samples were subjected to pasteurization at 65  degrees C
      for 30 min. Miniature cheeses were made by acidifying (pH=5.9) fortified milk and
      incubating with rennet for 1h at 32  degrees C. The clot formed was cut,
      centrifuged at 2,600 * g for 30 min at 20  degrees C and drained for determining
      cheese yield. Cheese-yielding capacity was expressed as actual yield (grams of
      cheese curd per 100g of milk) and dry weight yield (grams of dried cheese curd
      per 100g of milk). Free-zone capillary electrophoresis was used for determining
      beta-LG A or B recovery in the curd during rennet-induced coagulation. The
      presence of beta-LG variant B resulted in a significantly higher actual and dried
      weight cheese yield than when A or A-B were present at levels <= 0.675% of whey
      protein (WP) addition. Results of free-zone capillary electrophoresis allowed us
      to infer that beta-LG B associates with the casein micelles during renneting, as
      shown by an increase in the recovery of this variant in the curd when beta-LG B
      was added up to a maximum at 0.45% (equivalent to 0.675% WP). In general, actual
      or dried weight cheese yield increased as WP addition was increased from 0.225 to
      0.675%. However, when WP addition ranged from 0.675 to 0.90%, a drastic drop in
      cheese yield was observed. This behavior may be because an increase in the
      aggregation of casein micelles with a concomitant inclusion of whey protein in
      the gel occurs at low levels of WP addition, whereas once the association of WP
      with the casein micelles reach a saturation point at addition levels higher than
      0.675%, rearrangements of the gel network result in larger whey expulsion and
      syneresis. This knowledge is expected to be useful to maximize cheese yield and
      optimize processing conditions during cheese and cheese analogs manufacturing.

PMID- 24011943
TI  - Effect of milking frequency on the behavior and productivity of lactating dairy
      cows.
AB  - The objective of this study was to determine the effect of milking frequency on
      the behavioral patterns and productivity of lactating dairy cows. Twelve
      freestall-housed, lactating Holstein dairy cows (7 primiparous and 5 multiparous)
      were exposed to each of 2 treatments (over 21-d periods) in a replicated
      crossover design. Treatments were milking frequency of 2* /d (at 0600 and 1800 h)
      or 3* /d (at 0600, 1400, and 2200 h). Milk production, feeding, lying, and
      rumination behavior were monitored for each animal for the last 7d of each
      treatment period. Milk samples were collected for the last 3d of each period for
      milk component analysis. The results indicated that cows milked 3* /d produced
      2.9 kg/d more milk than those milked 2* /d. Primiparous cows consumed 3.9 kg/d
      less dry matter (DM) than did multiparous cows. The extra time (14.6 min/d)
      required for milking 3* /d altered the distribution of cow behavioral activity
      throughout the day. Although this did not affect total daily lying or rumination
      time, we observed a tendency for cows milked 2* /d to spend less time (224.6 vs.
      237.5 min/d) feeding and, thus, those cows tended to consume their feed at a
      faster rate (0.13 vs. 0.12 kg of DM/min) than cows milked 3* /d. For multiparous
      cows, the increase in feeding activity was facilitated through having longer
      (40.1 vs. 36.8 min/meal) and numerically larger meals (4.8 vs. 4.6 kg of DM/meal)
      when milked 3* /d. Alternatively, primiparous cows consumed smaller (2.9 vs. 3.2
      kg of DM/meal) and more frequent meals (9.1 vs. 7.7 meals/d) throughout the day
      when milked 3* /d, resulting in a tendency for greater DM intake (24.7 vs. 23.6
      kg/d) compared with primiparous cows milked 2* /d. These results indicate that
      under 3* /d milking schedules, primiparous cows will positively adjust their
      feeding behavior to achieve similar production increases as multiparous cows. In
      summary, milking 3* /d can be used to improve production; however, greater
      milking frequency elicits varying effects on the behavior of primiparous and
      multiparous cows, suggesting that grouping and management of cows based on parity
      may be beneficial.

PMID- 24011944
TI  - Effect of different feeding strategies in intensive dairy farming systems on milk
      fatty acid profiles, and implications on feeding costs in Italy.
AB  - The aim of this work was to characterize the fatty acid (FA) profile of milk from
      intensive dairy farming systems in the Po Plain (Italy) to estimate the costs of
      the adopted feeding strategies and to simulate the effect of supplementary
      premiums on the basis of milk FA composition on milk income. Twenty dairy farms
      with 5 different feeding strategies were studied: 3 corn silage-based systems in
      which cows were supplemented with a great proportion (CCH), a medium proportion
      (CCM), or without commercial concentrate mix (CC0), and 2 systems in which part
      of corn silage was replaced with grass or legume silage (HF) or with fresh
      herbage (G), cut and fed indoors. Bulk milk was sampled and lactating cow
      performance, feeding strategies and forage characteristics were recorded through
      a survey, 3 times during a year. The milk FA supplementary premium was calculated
      considering C18:3n-3 and saturated FA (SFA) concentrations, and ratio of total
      cis C18:1 isomers to C16:0. The CCH, CCM, and CC0 systems bought most of their
      dairy cow feeds off farm, which allowed them to increase milk production to
      35,000 L/yr per hectare. Their low dry matter and crude protein self-sufficiency
      led to higher feeding costs per liter of milk (from ?0.158 to ?0.184), and
      highest income over feed cost was achieved only for milk yield performance
      greater than 10,000 kg/cow per year. The use of homegrown forages in HF and G
      increased dry matter and crude protein self-sufficiency and reduced the feeding
      costs per liter of milk from 9 to 22%, compared with the other studied systems,
      making HF and G feeding economically competitive, even for a lower milk yield per
      cow. The studied systems highlighted a remarkable variation in FA profiles. The
      concentrations of C16:0 and SFA were the highest in CCH (31.53 and 67.84 g/100g
      of FA) and G (31.23 and 68.45 g/100g of FA), because of the larger proportion of
      commercial concentrate mix in the cow diet. The concentrations of C16:0 and SFA
      were the lowest in CCM (27.86 and 63.10 g/100g of FA), because of low roughage-to
      concentrate ratio in the cow diet, which is known to favor milk fat depression,
      affecting particularly these FA. The calculated supplementary premium was the
      highest in the CCM system, based on milk FA profiles from those herds. The HF
      diet was rich in forages and resulted in greater concentration of C18:3n-3 in
      milk (0.57 g/100g of FA) than the other systems and thus led to an increase in
      milk FA supplementary premium. Milk from G and HF milk had the lowest ratio of
      Sigman-6:Sigman-3 FA compared with milk from the systems based on higher corn
      silage proportion in the cow diet (3.71, and 3.25, respectively, vs. 4.58 to
      4.78), with the lower ratios being closer to recommendation for human nutrition.

PMID- 24011945
TI  - Applying additive logistic regression to data derived from sensors monitoring
      behavioral and physiological characteristics of dairy cows to detect lameness.
AB  - The hypothesis was that sensors currently available on farm that monitor
      behavioral and physiological characteristics have potential for the detection of
      lameness in dairy cows. This was tested by applying additive logistic regression
      to variables derived from sensor data. Data were collected between November 2010
      and June 2012 on 5 commercial pasture-based dairy farms. Sensor data from weigh
      scales (liveweight), pedometers (activity), and milk meters (milking order,
      unadjusted and adjusted milk yield in the first 2 min of milking, total milk
      yield, and milking duration) were collected at every milking from 4,904 cows.
      Lameness events were recorded by farmers who were trained in detecting lameness
      before the study commenced. A total of 318 lameness events affecting 292 cows
      were available for statistical analyses. For each lameness event, the lame cow's
      sensor data for a time period of 14 d before observation date were randomly
      matched by farm and date to 10 healthy cows (i.e., cows that were not lame and
      had no other health event recorded for the matched time period). Sensor data
      relating to the 14-d time periods were used for developing univariable (using one
      source of sensor data) and multivariable (using multiple sources of sensor data)
      models. Model development involved the use of additive logistic regression by
      applying the LogitBoost algorithm with a regression tree as base learner. The
      model's output was a probability estimate for lameness, given the sensor data
      collected during the 14-d time period. Models were validated using leave-one-farm
      out cross-validation and, as a result of this validation, each cow in the data
      set (318 lame and 3,180 nonlame cows) received a probability estimate for
      lameness. Based on the area under the curve (AUC), results indicated that
      univariable models had low predictive potential, with the highest AUC values
      found for liveweight (AUC=0.66), activity (AUC=0.60), and milking order
      (AUC=0.65). Combining these 3 sensors improved AUC to 0.74. Detection performance
      of this combined model varied between farms but it consistently and significantly
      outperformed univariable models across farms at a fixed specificity of 80%.
      Still, detection performance was not high enough to be implemented in practice on
      large, pasture-based dairy farms. Future research may improve performance by
      developing variables based on sensor data of liveweight, activity, and milking
      order, but that better describe changes in sensor data patterns when cows go
      lame.

PMID- 24011946
TI  - Effects of intrajugular glucose infusion on feed intake, milk yield, and
      metabolic responses of early postpartum cows fed diets varying in protein and
      starch concentration.
AB  - Effects of glucose infusion on feed intake, milk production, and metabolic
      responses of early postpartum cows fed diets varying in starch and protein
      concentration were evaluated by utilizing a randomized complete block design with
      a 2*2 factorial arrangement of treatments. Twenty-four multiparous Holstein cows
      were blocked by body condition score and 305-d mature-equivalent milk yield and
      randomly assigned at calving to 1 of 4 treatments. Treatments were continuous
      intrajugular infusion of glucose (GI) or isotonic saline (SI), and diets
      containing high starch, low crude protein (HSLP) or high crude protein, low
      starch (HPLS) concentrations. Treatments were initiated at the first scheduled
      feeding following parturition and lasted 12d. The GI reduced cumulative dry
      matter intake and tended to reduce daily dry matter intake and meal size for HPLS
      but not HSLP compared with SI. The GI increased cumulative milk yield by 39
      kg/12d compared with SI by increasing it for HSLP but not HPLS. The HPLS
      treatment tended to increase loss of body condition from 0.65 to 0.82 body
      condition score units/12d compared with HSLP. Consistent with this, HPLS
      increased plasma concentrations of nonesterified fatty acids, beta
      hydroxybutyrate, liver triglyceride, milk fat concentration and yield, 3.5% fat
      corrected milk, and milk urea nitrogen compared with HSLP. Overall, the GI-HPLS
      treatment reduced feed intake by reducing meal size. The GI-HPLS may have reduced
      meal size by the independent or additive effects of (1) decreasing hepatic
      gluconeogenesis and promoting oxidation of acetyl coenzyme A (CoA), (2) elevated
      plasma nonesterified fatty acids from HPLS increasing the pool of acetyl CoA
      available to be oxidized, and (3) the HPLS diet increasing urea synthesis, which
      also provides the tricarboxylic acid cycle intermediate fumarate to promote
      oxidation of acetyl CoA.

PMID- 24011947
TI  - Hyperkalemia in neonatal diarrheic calves depends on the degree of dehydration
      and the cause of the metabolic acidosis but does not require the presence of
      acidemia.
AB  - Hyperkalemia is a clinically important electrolyte imbalance in neonatal
      diarrheic calves that has previously been associated with skeletal muscle
      weakness and life-threatening cardiac arrhythmias. The aim of the present
      retrospective analysis was to identify risk factors for hyperkalemia in a
      convenience sample of 832 calves (<= 21 d of age) with a clinical diagnosis of
      diarrhea admitted to a veterinary teaching hospital. Plasma potassium
      concentrations were most closely associated with parameters of dehydration and
      renal function such as serum creatinine [Spearman correlation (rs) = 0.61], urea
      (rs = 0.51), and inorganic phosphorus concentrations (rs = 0.64). Plasma
      potassium concentrations were weakly associated with venous blood pH (rs = 
      0.21). Although venous blood pH was not predictive in a multivariate linear
      regression analysis, the odds of having hyperkalemia (>5.8 mmol/L) in acidemic
      calves was found to be 8.6 times as high as in nonacidemic calves [95% confidence
      interval (CI): 4.8-15.4]. However, the presence of hyperkalemia depended on the
      nature of an existing acidosis, and the odds for the presence of hyperkalemia in
      acidemic calves with hyper-D-lactatemia (>3.96 mmol/L) were only 0.15 times as
      high as in acidemic calves with normal D-lactate concentrations (95% CI, 0.11
      0.22). Acidemia in hyperkalemic diarrheic calves was associated with hyponatremia
      and increased concentrations of inorganic phosphorus, L-lactate, and unidentified
      strong anions that presumably included uremic anions such as sulfate. We conclude
      that hyper-D-lactatemia in neonatal diarrheic calves is not usually associated
      with elevated plasma potassium concentrations. Application of the simplified
      strong ion acid-base model indicated that dehydration is an important contributor
      to the pathogenesis of hyperkalemia and acidemia in neonatal calves with
      diarrhea.

PMID- 24011948
TI  - Effect of chemical form, heating, and oxidation products of linoleic acid on
      rumen bacterial population and activities of biohydrogenating enzymes.
AB  - Heating polyunsaturated fatty acids (PUFA) produces oxidation products, such as
      hydroperoxides, aldehydes, and oxypolymers, which could be responsible at least
      in part for modification of PUFA rumen biohydrogenation (BH). Three in vitro
      experiments were conducted to investigate the effects of linoleic acid (cis-9,cis
      12-C18:2) oxidation products on BH. In the first experiment, we studied the
      effects of free linoleic acid (FLA), heated FLA (HFLA, at 150  degrees C for 6h),
      triacylglycerols of linoleic acid (TGLA), heated TGLA (HTGLA, at 150  degrees C
      for 6h), 13-hydroperoxide (13HPOD), trans-2-decenal (T2D), and hexanal (HEX) on
      BH in vitro after 6 and 24h of incubation. In the second experiment, aldehydes
      differing in chain length and degree of unsaturation [pentanal, HEX, heptanal,
      nonanal, T2D, trans-2,trans-4-decadienal (T2T4D)] were incubated in vitro for 5h
      in rumen fluid. In the third experiment, 9-hydroperoxide (9HPOD), 13HPOD, HEX, or
      T2T4D were incubated for 1h in rumen fluid inactivated with chloramphenicol to
      investigate their effects on enzyme activity. In experiment 1, heat treatment of
      TGLA generated TGLA oxypolymers, did not affect cis-9,cis-12-C18:2 disappearance,
      but did decrease BH intermediates, especially trans-11 isomers. Heating FLA
      decreased cis-9,cis-12-C18:2 disappearance and cis-9,trans-11-CLA and trans-11
      C18:1 production. Treatment with HEX and T2D did not affect cis-9,cis-12-C18:2
      disappearance and barely affected production of BH intermediates. The bacterial
      community was affected by 13HPOD compared with FLA and HFLA, in parallel with an
      increase in trans-10 isomer production after a 6-h incubation. After 24h of
      incubation, 13HPOD decreased trans-11 isomer production, but to a lesser extent
      than HFLA. In experiment 2, some weak but significant effects were observed on
      BH, unrelated to chain length or degree of unsaturation of aldehydes; the
      bacterial community was not affected. In experiment 3, 9HPOD inhibited Delta(9)
      isomerization, and both 9HPOD and 13HPOD inhibited Delta(12)-isomerization. We
      concluded that oxypolymers did not affect cis-9,cis-12-C18:2 disappearance.
      Heating both esterified and free cis-9,cis-12-C18:2 greatly altered Delta(12)
      isomerization. Aldehydes had few effects. Hydroperoxides are responsible, at
      least in part, for the effects of fat heating: 13HPOD increased trans-10 isomer
      production (probably by affecting the bacterial community) and decreased trans-11
      isomer production by inhibiting Delta(12)-isomerase activity, whereas 9HPOD
      inhibited both isomerases.

PMID- 24011949
TI  - Palmitic acid increased yields of milk and milk fat and nutrient digestibility
      across production level of lactating cows.
AB  - The effects of palmitic acid supplementation on feed intake, digestibility, and
      metabolic and production responses were evaluated in dairy cows with a wide range
      of milk production (34.5 to 66.2 kg/d) in a crossover design experiment with a
      covariate period. Thirty-two multiparous Holstein cows (151 +/- 66 d in milk)
      were randomly assigned to treatment sequence within level of milk production.
      Treatments were diets supplemented (2% of diet DM) with palmitic acid (PA; 99%
      C16:0) or control (SH; soyhulls). Treatment periods were 21 d, with the final 4 d
      used for data and sample collection. Immediately before the first treatment
      period, cows were fed the control diet for 21 d and baseline values were obtained
      for all variables (covariate period). Milk production measured during the
      covariate period (preliminary milk yield) was used as covariate. In general, no
      interactions were detected between treatment and preliminary milk yield for the
      response variables measured. The PA treatment increased milk fat percentage (3.40
      vs. 3.29%) and yields of milk (46.0 vs. 44.9 kg/d), milk fat (1.53 vs. 1.45
      kg/d), and 3.5% fat-corrected milk (44.6 vs. 42.9 kg/d), compared with SH.
      Concentrations and yields of protein and lactose were not affected by treatment.
      The PA treatment did not affect dry matter (DM) intake or body weight, tended to
      decrease body condition score (2.93 vs. 2.99), and increased feed efficiency
      (3.5% fat-corrected milk/DM intake; 1.60 vs. 1.54), compared with SH. The PA
      treatment increased total-tract digestibility of neutral detergent fiber (39.0
      vs.35.7%) and organic matter (67.9 vs. 66.2%), but decreased fatty acid (FA)
      digestibility (61.2 vs. 71.3%). As total FA intake increased, total FA
      digestibility decreased (R(2) = 0.51) and total FA absorbed increased (quadratic
      R(2) = 0.82). Fatty acid yield response, calculated as the additional FA yield
      secreted in milk per unit of additional FA intake, was 11.7% for total FA and
      16.5% for C16:0 plus cis-9 C16:1 FA. The PA treatment increased plasma
      concentration of nonesterified FA (101 vs. 90.0 MUEq/L) and cholecystokinin (19.7
      vs. 17.6 pmol/L), and tended to increase plasma concentration of insulin (10.7
      vs. 9.57 MU IU/mL). Results show that palmitic acid fed at 2% of diet DM has the
      potential to increase yields of milk and milk fat, independent of production
      level without increasing body condition score or body weight. However, a small
      percentage of the supplemented FA was partitioned to milk.

PMID- 24011950
TI  - Unique interrelationships between fiber composition, water-soluble carbohydrates,
      and in vitro gas production for fall-grown oat forages.
AB  - Sixty samples of 'ForagePlus' oat were selected from a previous plot study for
      analysis of in vitro gas production (IVGP) on the basis of 2 factors: (1) high
      (n=29) or low (n=31) neutral detergent fiber (NDF; 62.7+/-2.61 and 45.1+/-3.91%,
      respectively); and (2) the range of water-soluble carbohydrates (WSC) within the
      high- and low-NDF groups. For the WSC selection factor, concentrations ranged
      from 4.7 to 13.4% (mean=7.9+/-2.06%) and from 3.5 to 19.4% (mean=9.7+/-4.57%)
      within high- and low-NDF forages, respectively. Our objectives were to assess the
      relationships between IVGP and various agronomic or nutritional characteristics
      for high- and low-NDF fall-oat forages. Cumulative IVGP was fitted to a single
      pool nonlinear regression model: Y=MAX * (1 - e ([-)(K)(* (t - lag)])), where
      Y=cumulative gas produced (mL), MAX=maximum cumulative gas produced with infinite
      incubation time (mL), K=rate constant, t=incubation time (h), and lag=discrete
      lag time (h). Generally, cumulative IVGP after 12, 24, 36, or 48h within high-NDF
      fall-oat forages was negatively correlated with NDF, hemicellulose, lignin, and
      ash, but positively correlated with WSC, nonfiber carbohydrate (NFC), and total
      digestible nutrients (TDN). For low-NDF fall-grown oat forages, IVGP was
      positively correlated with growth stage, canopy height, WSC, NFC, and TDN;
      negative correlations were observed with ash and crude protein (CP) but not
      generally with fiber components. These responses were also reflected in multiple
      regression analysis for high- and low-NDF forages. After 12, 24, or 36h of
      incubation, cumulative IVGP within high-NDF fall-oat forages was explained by
      complex regression equations utilizing (lignin:NDF)(2), lignin:NDF,
      hemicellulose, lignin, and TDN(2) as independent variables (R(2)>=0.43). Within
      low-NDF fall-grown oat forages, cumulative IVGP at these incubation intervals was
      explained by positive linear relationships with NFC that also exhibited high
      coefficients of determination (R(2)>=0.75). Gas production was accelerated at
      early incubation times within low-NDF forages, specifically in response to large
      pools of WSC that were most likely to be present as forages approached boot stage
      by late-fall. 

PMID- 24011951
TI  - Supplemental progesterone and timing of resynchronization on pregnancy outcomes
      in lactating dairy cows.
AB  - The objective was to determine the effect of exogenous progesterone (P4) in a
      timed artificial insemination (TAI) protocol initiated at 2 different times post
      AI on pregnancies per AI (P/AI) in lactating dairy cows. Cows (n=1,982) in 5
      dairy herds were assigned randomly at a nonpregnancy diagnosis 32 +/- 3 d post-AI
      to 1 of 4 resynchronization (RES) treatments arranged in a 2 * 2 factorial design
      using the Ovsynch-56 (GnRH, 7d later PGF2alpha, 56 h later GnRH, 16 h later TAI)
      protocol. Treatments were as follows: cows initiating RES 32 +/- 3 d after AI
      with no supplemental P4 (d 32 RES-CON; n=516); same as d 32 RES-CON plus a
      controlled internal drug release (CIDR) insert containing P4 at the onset of
      Ovsynch-56 (d 32 RES-CIDR; n=503); cows initiating RES 39 +/- 3 d after AI (d 39
      RES-CON; n=494); and same as d 39 RES-CON plus a CIDR (d 39 RES-CIDR; n=491).
      Cows were inseminated if observed in estrus before TAI. The P/AI was determined
      32 and 60 d after TAI. In a subgroup of cows (n=1,152), blood samples were
      collected and ovarian structures examined by ultrasonography on the days of the
      first GnRH (G1) and PGF2alpha of Ovsynch-56. Percentage of cows with a corpus
      luteum (CL) at G1 was unaffected by timing of treatments, but percentage of cows
      with a CL at PGF2alpha was greater for d 32 than for d 39 cows (87.9 vs. 79.4%).
      In addition, percentage of cows with P4 >= 1 ng/mL at G1 was unaffected by timing
      of treatments, but was increased for d 32 compared with d 39 RES cows on the day
      of the PGF2alpha of the RES protocols (86.5 vs. 74.3%). Treatment did not affect
      ovulation to G1 or P/AI 32 d after RES TAI (d 32 RES-CON=30.1%, d 32 RES
      CIDR=28.8%, d 39 RES-CON=27.5%, d 39 RES-CIDR=30.5%). A greater percentage of d
      39 RES cows underwent premature luteolysis during the RES protocol compared with
      d 32 RES cows. An interaction was detected between day of RES initiation and CIDR
      treatment, in which the CIDR increased P/AI 60 d after TAI for d 39 (CON=23.7%
      vs. CIDR=28.0%), but not for d 32 (CON=26.9% and CIDR=24.2%) cows. Pregnancy loss
      was unaffected by treatment. In addition, cows had improved P/AI 60 d after TAI
      when they received a CIDR and did not have a CL (CON-CL=28.2%, CON-No CL=19.2%,
      CIDR-CL=27.0%, and CIDR-No CL=26.5%) or had P4 <1 ng/mL (CON-High P4=27.8%, CON
      Low P4=15.0%, CIDR-High P4=25.0%, and CIDR-Low P4=29.4%) at G1, but not if a CL
      was present or P4 was >= 1 ng/mL at G1. In conclusion, addition of a CIDR insert
      to supplement P4 during the RES protocol increased P/AI for cows initiating RES
      39 +/- 3 d after AI but not 32 +/- 3 d after AI.

PMID- 24011952
TI  - Alteration in the Wnt/beta-catenin signaling pathway in gastric neoplasias of
      fundic gland (chief cell predominant) type.
AB  - Gastric neoplasia of chief cell-predominant type (GN-CCP) has been reported as a
      new, rare variant of gastric tumor. GN-CCPs were defined as tumors consisting of
      irregular anastomosing glands of columnar cells mimicking chief cells of fundic
      gland with nuclear atypia and prolapse-type submucosal involvement. We
      comparatively evaluated clinicopathologic features between 31 GN-CCPs and 130
      cases of conventional gastric adenocarcinoma invading into submucosa (CGA-SM) in
      addition to nuclear beta-catenin immunolabeling and direct sequencing of members
      of the Wnt/beta-catenin pathway, CTNNB1, APC, and AXIN, in a subset of these
      tumors. GN-CCP presented as small protruded lesions located in the upper third of
      the stomach, with minimal involvement into the submucosa and rare lymphovascular
      invasion. None of the lesions have demonstrated a recurrence of disease or
      metastasis on follow-up. Nuclear beta-catenin immunolabeling was higher in GN-CCP
      (labeling index [LI]: median, 19.3%; high expresser [LI >30%], 7/27 cases [26%])
      than CGA-SM (median LI, 14.7%; high expresser, 1/19 cases [6%]). Missense
      mutation of APC was observed in 1 GN-CCP but not CGA-SM. Missense or nonsense
      mutations of CTNNB1 and AXIN1 were higher in GN-CCPs (14.8%, both) than CGA-SMs
      (5.3%, both). Missense mutations of AXIN2 were higher in GN-CCPs (25.9%) than in
      CGA-SMs (10.5%). Overall, 14 (51.9%) of 27 GN-CCPs and 5 (26.3%) of 19 CGA-SM
      cases harbored at least 1 of these gene mutations. In conclusion, GN-CCPs as a
      unique variant of nonaggressive tumor are characterized by nuclear beta-catenin
      accumulation and mutation of CTNNB1 or AXIN gene, suggesting activation of the
      Wnt/beta-catenin pathway.

PMID- 24011953
TI  - Defining a prognostic marker panel for patients with ovarian serous carcinoma
      effusion.
AB  - Advanced-stage ovarian carcinoma is a highly lethal malignancy, yet no widely
      accepted prognostic panels exist to date in this disease. The objective of this
      study was to define such panel for patients with ovarian serous carcinoma
      effusions. The expression by immunohistochemistry and clinical role of 41
      previously studied cancer-associated proteins was analyzed in 143 effusions from
      patients diagnosed as having advanced-stage (International Federation of
      Gynecology and Obstetrics stages III-IV) ovarian serous carcinoma treated with
      platinum-based chemotherapy at diagnosis. Survival analyses were performed
      separately for patients with prechemotherapy and postchemotherapy effusions. In
      univariate analysis of patients with primary diagnosis prechemotherapy effusions,
      survivin was associated with longer progression-free survival (P = .03), whereas
      survivin (P = .009), signal transducer and activator of transcription 5B (P =
      .011), and p21-activated kinase-1 (P = .04) were markers of longer overall
      survival. In univariate analysis of patients with disease recurrence
      postchemotherapy effusions, peroxisome proliferator-activated receptor-gamma (P =
      .004), human leukocyte antigen-G (P = .013), mammalian target of rapamycin (P =
      .04), and nucleus accumbens 1 (NAC-1) (P = .046) were associated with poor
      progression-free survival, whereas peroxisome proliferator-activated receptor
      gamma (P = .013), claudin-3 (P = .019), activator protein-2gamma (P = .04),
      insulin-like growth factor-2 (P = .04), claudin-7 (P = .042), and fatty acid
      synthase (P = .048) were markers of poor overall survival. In Cox multivariate
      analysis for prechemotherapy cases, survivin and fatty acid synthase were
      independent predictors of better progression-free survival (P = .006 and P =
      .048, respectively), and signal transducer and activator of transcription 5B and
      heat shock protein 90 were independently associated with better overall survival
      (P = .033 and P = .006, respectively). None of the biological markers was an
      independent prognostic factor in recurrent disease. The present study represents
      the first attempt at prognostic stratification of multiple tumor markers in one
      cohort of patients with ovarian serous carcinoma effusions. 

PMID- 24011954
TI  - Discovery and characterization of synthetic 4'-hydroxyflavones-New CK2 inhibitors
      from flavone family.
AB  - Human protein kinase CK2 is one of the most intriguing enzymes, which functional
      role still remains unclear despite of decades of studying. At present there is
      abundant evidence pointing to the fact that inhibitors of CK2 could be used as
      pharmaceutical agents to treat cancer, viral infections and inflammatory
      diseases. Here we report novel synthetic flavone inhibitors, 4'-hydroxyflavones,
      possessing high activity towards CK2. These compounds were identified with
      receptor-based virtual screening and then chemically optimized on the base of
      rationale derived from biochemical screening and molecular modeling. It has been
      demonstrated that synthetic flavone derivatives are much more potent CK2
      inhibitors than the natural ones, and we believe that their further examination
      will be helpful for studying biological role of CK2 as well as for development of
      new kinase-oriented drugs. 

PMID- 24011955
TI  - Impact of weight on treatment efficacy and safety in complicated skin and skin
      structure infections and nosocomial pneumonia caused by methicillin-resistant
      Staphylococcus aureus.
AB  - BACKGROUND: There are few data on dose optimization and clinical outcomes of
      antimicrobial agents based on patients' weight, despite the rising prevalence of
      obesity. Because there are physiologic, pharmacologic, and dosing differences
      related to weight, it is important to evaluate the impact of weight on
      antimicrobial agents to optimize clinical outcomes. OBJECTIVES: This study
      compared effects of weight on efficacy and safety in patients treated with
      linezolid or vancomycin for complicated skin and skin structure infections
      (cSSSIs) and nosocomial pneumonia (NP) caused by methicillin-resistant
      Staphylococcus aureus (MRSA). METHODS: We analyzed data from 2 clinical trials of
      patients randomized to receive a fixed dose of linezolid or weight-based dosing
      of vancomycin for the treatment of cSSSIs or NP caused by MRSA. For each study,
      patients were stratified into quartiles (Q1-4 [lowest to highest weight,
      respectively]). Clinical success, microbiologic success, and adverse events (AEs)
      were evaluated. RESULTS: The analysis included 632 patients with cSSSIs
      (linezolid, n = 316; vancomycin, n = 316) and 447 patients with NP (linezolid, n
      = 224; vancomycin, n = 223). Among patients with cSSSIs, clinical success rates
      at the study end with fixed-dose linezolid were similar across all weight
      quartiles and similar to weight-based dosing of vancomycin for Q1-3. Among Q4
      (the highest weight quartile [97-295 kg]), clinical success with vancomycin was
      significantly lower compared with linezolid (69.5% vs 86.2%; P = 0.03). Among
      patients with NP, no significant differences in success rates between fixed-dose
      linezolid and weight-based dosing of vancomycin were observed across all
      quartiles. Frequencies of AEs were consistent across the quartiles for both
      indications and by treatment. CONCLUSIONS: Except for Q4 within the vancomycin
      treated patients for MRSA cSSSI, the efficacy of fixed-dosed linezolid and weight
      based dosing of vancomycin was maintained across all weight quartiles and MRSA
      infection types. The AEs were consistent with the known safety profiles of each
      drug regardless of weight quartile. ClinicalTrials.gov identifiers: NCT00087490
      and NCT00084266.

PMID- 24011956
TI  - Comparisons of surface vs. volumetric model-based registration methods using
      single-plane vs. bi-plane fluoroscopy in measuring spinal kinematics.
AB  - Several 2D-to-3D image registration methods are available for measuring 3D
      vertebral motion but their performance has not been evaluated under the same
      experimental protocol. In this study, four major types of fluoroscopy-to-CT
      registration methods, with different use of surface vs. volumetric models, and
      single-plane vs. bi-plane fluoroscopy, were evaluated: STS (surface, single
      plane), VTS (volumetric, single-plane), STB (surface, bi-plane) and VTB
      (volumetric, bi-plane). Two similarity measures were used: 'Contour Difference'
      for STS and STB and 'Weighted Edge-Matching Score' for VTS and VTB. Two cadaveric
      porcine cervical spines positioned in a box filled with paraffin and embedded
      with four radiopaque markers were CT scanned to obtain vertebral models and
      marker coordinates, and imaged at ten static positions using bi-plane fluoroscopy
      for subsequent registrations using different methods. The registered vertebral
      poses were compared to the gold standard poses defined by the marker positions
      determined using CT and Roentgen stereophotogrammetry analysis. The VTB was found
      to have the highest precision (translation: 0.4mm; rotation: 0.3 degrees ),
      comparable with the VTS in rotations (0.3 degrees ), and the STB in translations
      (0.6mm). The STS had the lowest precision (translation: 4.1mm; rotation: 2.1
      degrees ). 

PMID- 24011957
TI  - A mitochondrial implication in a Tunisian patient with Friedreich's ataxia-like.
AB  - Genes encoding the DNA helicase TWINKLE (C10orf2) or the two subunits of mtDNA
      polymerase gamma (POLgamma) (POLG1 and POLG2) have a direct effect on the
      mitochondrial DNA replication machinery and were reported in many mitochondrial
      disorders. Friedreich's ataxia (FRDA) is the common cause of ataxia often
      associated with the expansion of a GAA repeat in intron 1 of the frataxin gene
      (FXN). Mitochondrial DNA could be considered as a candidate modifier factor for
      FRDA disease, since mitochondrial oxidative stress is thought to be involved in
      the pathogenesis of this disease. We screened the FXN, POLG1 and C10orf2 genes in
      a Tunisian patient with clinical features of Friedreich's ataxia-like. The
      results showed the absence of the expansion of a GAA triplet repeat in intron 1
      of the FXN gene. Besides, the sequencing of all the exons and their flanking
      regions of the FXN, POLG1 and C10orf2 genes revealed the presence of intronic
      polymorphisms. In addition, screening of the mtDNA revealed the presence of
      several mitochondrial known variations and the absence of mitochondrial deletions
      in this patient. The detected m.16187C>T and the m.16189T>C change the order of
      the homopolymeric tract of cytosines between 16184 and 16193 in the mitochondrial
      D-loop and could lead to a mitochondrial dysfunction by inhibiting replication
      and affecting protein involved in the replication process of the mtDNA which
      could be responsible for the clinical features of Friedreich ataxia observed in
      the studied patient.

PMID- 24011958
TI  - [Social connection: a report of the SFGM-TC on the maintaining social and family
      connections during Hematopoietic Stem Cell Transplantation].
AB  - OBJECTIVE: To set up the minimal conditions necessary to ensure that the social
      and familial network of the patient is preserved during the hospital stay for
      allogeneic hematopoietic stem cell transplantation. MATERIAL AND METHODS: A
      national survey was conducted to increase knowledge about the conditions of
      hospital stay of adult and pediatric stem cell recipients. Then a
      multidisciplinary panel of health workers including doctors and nurses met to
      establish recommendations for maintaining the social and familial relationships
      optimally during the HSCT procedure. RESULTS: Practices and policies are very
      heterogeneous among the transplant centers. No consensus has been established and
      the literature data are scarce. The panel has thus established a list of
      recommendations to maintain optimal relationships between the patient and his
      relatives and friends during the hospital stay. The objective is to ensure a
      better acceptation of the isolation conditions and to facilitate the return home
      after D30. CONCLUSION: Since there is no established scientific background for
      drastic isolation conditions, a multi-disciplinary approach in relationship with
      patients associations should allow softening of the procedures without impairing
      the quality of care.

PMID- 24011959
TI  - [How I manage respiratory syncytial virus, human herpesvirus 6 and adenovirus
      reactivation or infection after allogeneic stem cell transplantation: a report of
      the SFGM-TC].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here we report our results and recommendations regarding the management of
      virus respiratory syncytial virus (RSV), human herpes virus 6 (HHV6) or
      adenovirus allogeneic Stem Cell Transplantation. 

PMID- 24011960
TI  - [How to handle unexpected biological abnormalities observed in the pre-donation
      workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre
      transplant cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or syphilis
      IgM positive serology test].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here we report our results and recommendations regarding the management of
      pre-transplant donor's cytomegalovirus, Epstein-Barr virus, Toxoplasma gondii, or
      syphilis IgM positive serology test. 

PMID- 24011961
TI  - [Diagnosis and treatment of CMV and EBV Reactivation as well as Post-transplant
      Lymphoproliferative Disorders following Allogeneic Stem Cell Transplantation: An
      SFGM-TC report].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here the SFGM-TC addressed the issue of post-transplant CMV and EBV
      reactivation, and EBV-related Lymphoproliferative Disorders. 

PMID- 24011962
TI  - [A report of the SFGM-TC on the interactions between national transplant
      coordination and local coordinators in allogeneic stem cell transplantation
      activity].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. The main aim of this session was to describe the relations between the
      national transplant coordination office of the French registry and local stem
      cell transplantation coordinators throughout France.

PMID- 24011963
TI  - [Management of endocrine dysfunctions after allogeneic hematopoietic stem cell
      transplantation: a report of the SFGM-TC on adrenal insufficiency and
      osteoporosis].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here we report our results and recommendations regarding the management of
      short and long-term endocrine dysfunction following allogeneic stem cell
      transplantation. The key aim of this workshop was to give an overview on
      secondary adrenal insufficiency and osteoporosis post-transplant.

PMID- 24011964
TI  - [Vaccination post hematopoietic stem cell transplantation: which vaccines and
      when and, how to vaccinate? An SFGM-TC report].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here we report our results and recommendations regarding vaccination post
      Hematopoietic Stem Cell Transplantation with practical focus on which vaccines to
      use and when and how to vaccinate?

PMID- 24011965
TI  - [How to handle unexpected biological abnormalities observed in the pre-donation
      workup for hematopoietic stem cell transplantation: an SFGM-TC report on pre
      transplant positive pregnancy test and monoclonal gammapathy].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here we report our results and recommendations regarding the management of
      common issues related to the donor: pre-transplant pregnancy and monoclonal
      gammopathy. 

PMID- 24011966
TI  - Serum haptoglobin in clinical biochemistry: change of a paradigm.
AB  - Serum haptoglobin (Hp) was discovered by Max Fernand Jayle as a young assistant
      professor in the Department of Biochemistry of the Paris Medical Faculty, headed
      by Professor Michel Polonovski. Jayle showed that Hp was an acute phase
      glycoprotein and worked out its routine determination in the blood-serum, based
      on its complex formation with hemoglobin, using the increased peroxidase activity
      of the hemoglobin-haptoglobin (Hb-Hp) complex, for routine determination in
      clinical biochemistry for the characterisation of inflammatory processes,
      together with other acute phase glycoproteins as orosomucoide. Later Smithies
      described the genetic control of human Hp-isoforms and quite recently Andersen et
      al. reported the elucidation of the crystal structure of the porcine Hb-Hp
      complex. In that article there was no mention of the discovery of Hp, neither of
      its determination in clinical biochemistry as an inflammatory marker. The only
      biologically significant role assigned to Hp by Andersen et al. is its
      (hypothetical) role to prevent or minimize the harmful effects of Hb during
      intravascular hemolysis, by the generation of reactive oxygen species (ROS) and
      complexing it. This shift of paradigm, not at all exceptional in medical
      biochemistry, will be described and discussed with its pitfalls and consequences.

PMID- 24011967
TI  - [Management of endocrine dysfunctions after allogeneic hematopoietic stem cell
      transplantation: a report of the SFGM-TC on dyslipidemia and thyroid disorders].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here we report our results and recommendations regarding the management of
      short and long-term endocrine dysfunction following allogeneic stem cell
      transplantation. The key aim of this workshop was to give an overview on
      dyslipidemia and thyroid disorders post-transplant. 

PMID- 24011968
TI  - [Management of endocrine dysfunctions after allogeneic hematopoietic stem cell
      transplantation: a report of the SFGM-TC on gonadal failure and fertility].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here we report our results and recommendations regarding the management of
      short and long-term endocrine dysfunction following allogeneic stem cell
      transplantation. The key aim of this workshop was to give an overview gonadal
      failure, fertility preservation and post-transplant. 

PMID- 24011969
TI  - [Hematopoietic Stem Cell Transplantation using unrelated cord blood: which unit
      to choose? A report of the SFGM-TC].
AB  - In the attempt to harmonize clinical practices between different French
      transplantation centers, the French Society of Bone Marrow Transplantation and
      Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought
      together practitioners from all member centers and took place in October 2012 in
      Lille. Here we report our results and recommendations regarding the choice of
      optimal unrelated cord blood unit in terms of cell dose, HLA-matching and other
      characteristics. 

PMID- 24011970
TI  - Production characteristics of N2O during stabilization of municipal solid waste
      in an intermittent aerated semi-aerobic bioreactor landfill.
AB  - An intermittent aerated semi-aerobic bioreactor landfill has the advantages such
      as accelerating stabilization of municipal solid waste (MSW), reducing methane,
      and in situ nitrogen removal. However, the introduction of air into a nutrient
      rich environment induces nitrification and denitrification processes, as well as
      the potential to generate N species at intermediate oxidation states, including
      nitrous oxide (N2O). In this study, a simulated intermittent aerated semi-aerobic
      bioreactor landfill was designed and operated for 262 d in order to establish the
      production characteristics of N2O. The N2O concentration changed significantly
      with the degree of MSW stabilization, a low concentration level ranged from
      undetectable to 100 ppm in the initial stabilization period, then one or two
      orders of magnitude higher in the later stabilization period compared with the
      initial period. It is clear that N2O production is relevant to the biodegradable
      organics in leachate and refuse. Once the biodegradable carbon sources were
      insufficient, which limited the activity of denitrifying organisms, higher N2O
      production began.

PMID- 24011971
TI  - A comprehensive metabolic evaluation reveals impaired glucose metabolism and
      dyslipidemia in breast cancer patients early in the disease trajectory.
AB  - BACKGROUND & AIMS: Weight gain in breast cancer patients during treatment is
      prevalent; the metabolic implications of this weight gain are poorly understood.
      We aimed to characterize glucose metabolism in breast cancer patients near the
      initiation of chemotherapy. METHODS: Stage I-II breast cancer patients (n = 8)
      were evaluated near the initiation of chemotherapy and compared with a group of
      age- and body mass index-matched, as well as a group of young healthy, non
      malignant females. Fasting blood samples (analyzed for lipids and cytokines) were
      taken and an oral glucose tolerance test was performed. Body composition, waist
      circumference, diet, cardiovascular fitness and muscle strength were evaluated.
      RESULTS: Breast cancer patients were abdominally obese (mean +/- SD: 94.6 +/-
      14.0 cm), overweight (28.8 +/- 6.0 kg/m(2)) and dyslipidemic (triacylglycerides:
      1.84 +/- 1.17 mM; high-density lipoprotein cholesterol: 1.08 +/- 0.23 mM).
      Compared to non-malignant matched females, fasting glucose and insulin
      concentrations were similar but fasting c-peptide was greater in patients (2.6 +/
      1.2 ng/mL vs. 1.9 +/- 0.8 ng/mL, p = 0.005). Glucose was elevated to a greater
      extent in patients during the oral glucose tolerance test compared with all non
      malignant females. During the glucose tolerance test, c-peptide, but not insulin,
      remained elevated in patients compared with all non-malignant females. No
      differences in body composition, serum cytokines, nutrition or exercise capacity
      between patients and matched, non-malignant females emerged. CONCLUSIONS: Breast
      cancer patients present with unhealthy metabolic features early in the disease
      trajectory. Future investigations need to examine the underlying mechanisms and
      the potential longitudinal changes following chemotherapy.

PMID- 24011972
TI  - A comparison of the performances of an artificial neural network and a regression
      model for GFR estimation.
AB  - BACKGROUND: Accurate estimation of glomerular filtration rate (GFR) is important
      in clinical practice. Current models derived from regression are limited by the
      imprecision of GFR estimates. We hypothesized that an artificial neural network
      (ANN) might improve the precision of GFR estimates. STUDY DESIGN: A study of
      diagnostic test accuracy. SETTING & PARTICIPANTS: 1,230 patients with chronic
      kidney disease were enrolled, including the development cohort (n=581), internal
      validation cohort (n=278), and external validation cohort (n=371). INDEX TESTS:
      Estimated GFR (eGFR) using a new ANN model and a new regression model using age,
      sex, and standardized serum creatinine level derived in the development and
      internal validation cohort, and the CKD-EPI (Chronic Kidney Disease Epidemiology
      Collaboration) 2009 creatinine equation. REFERENCE TEST: Measured GFR (mGFR).
      OTHER MEASUREMENTS: GFR was measured using a diethylenetriaminepentaacetic acid
      renal dynamic imaging method. Serum creatinine was measured with an enzymatic
      method traceable to isotope-dilution mass spectrometry. RESULTS: In the external
      validation cohort, mean mGFR was 49+/-27 (SD) mL/min/1.73 m2 and biases (median
      difference between mGFR and eGFR) for the CKD-EPI, new regression, and new ANN
      models were 0.4, 1.5, and -0.5 mL/min/1.73 m2, respectively (P<0.001 and P=0.02
      compared to CKD-EPI and P<0.001 comparing the new regression and ANN models).
      Precisions (IQRs for the difference) were 22.6, 14.9, and 15.6 mL/min/1.73 m2,
      respectively (P<0.001 for both compared to CKD-EPI and P<0.001 comparing the new
      ANN and new regression models). Accuracies (proportions of eGFRs not deviating
      >30% from mGFR) were 50.9%, 77.4%, and 78.7%, respectively (P<0.001 for both
      compared to CKD-EPI and P=0.5 comparing the new ANN and new regression models).
      LIMITATIONS: Different methods for measuring GFR were a source of systematic bias
      in comparisons of new models to CKD-EPI, and both the derivation and validation
      cohorts consisted of a group of patients who were referred to the same
      institution. CONCLUSIONS: An ANN model using 3 variables did not perform better
      than a new regression model. Whether ANN can improve GFR estimation using more
      variables requires further investigation.

PMID- 24011973
TI  - Vitamin A treatment for psoriasis vulgaris in a dialysis patient.

PMID- 24011974
TI  - Commentary on "the standard of care and conflicts at the end of life: a review of
      decisions by the Ontario Consent and Capacity Board".

PMID- 24011975
TI  - Six-day postoperative impact of a standardized nurse observation and escalation
      protocol: a preintervention and postintervention study.
AB  - PURPOSE: The purpose of the study is to determine the impact of a standardized
      nurse observation and escalation protocol on observation frequency, the
      measurement of vital signs, and the incidence of in-hospital mortality and
      resurgery. METHODS: This is a preintervention and postintervention study by
      analysis of patient records for a 6-day postoperative period of all adult
      patients hospitalized in 4 hospital wards after surgery during a preintervention
      (November 2010 to March 2011; n = 2359) and postintervention (November 2011 to
      March 2012; n = 1888) period implementing a standardized nurse observation and
      escalation protocol including the Modified Early Warning Score. RESULTS: The mean
      patient observation frequency per nursing shift increased from 0.9076 (95%
      confidence interval [CI], 0.8921-0.9231) preintervention to 0.9940 (95% CI,
      0.9708-1.0172; P < .001) postintervention and was lower in case of 6-day
      postoperative mortality (0.6686 [95% CI, 0.4984-0.8388] vs other patients 0.9475
      [95% CI, 0.9340-0.9610]; P = .003) or resurgery (0.8402 [95% CI, 0.7894-0.8909]
      vs other patients 0.9564 [95% CI, 0.9378-0.9657]; P = .003). The mean number of
      vital signs measured per observation episode increased from a mean of 1.81 (95%
      CI, 1.79-1.83) preintervention to 2.45 (95% CI, 2.39-2.51; P < .001)
      postintervention. The relative risk reduction was 73.7% (95% CI, 22.8-91.0; P =
      .015) for 6-day postoperative in-hospital mortality and 30.9% (95% CI, 9.5-47.2;
      P = .007) for 6-day postoperative resurgery.

PMID- 24011976
TI  - Assessment of right ventricular functions in patients with sepsis, severe sepsis
      and septic shock and its prognostic importance: a tissue Doppler study.
AB  - PURPOSE: This study aims to investigate the potential contributions of the right
      ventricle (RV) performance evaluated using tissue Doppler imaging (TDI) on the
      assessment of the severity and prognosis of sepsis. METHODS: The study was
      completed with 55 patients (male/female 26/29, age 66.9 +/- 20.3 years) and 28
      healthy controls (male/female 14/14, age 59.4 +/- 18.3 years). The RV-TDI
      parameters, mainly the RV myocardial peak systolic velocities (Sm, cm/s) and
      myocardial performance index (MPI) were recorded, in addition to the standard
      echocardiographic evaluation. RESULTS: The patients were classified into 3 groups
      based on the severity of sepsis. The RV-Sm value was significantly lower in the
      severe sepsis-septic shock (n = 31) than that of the sepsis (n = 24) and the
      control groups (n = 28) (P = .001). The RV-MPI was high both in the severe sepsis
      septic shock and the sepsis compared with the control group (P = .02). The
      patients were classified into 3 groups based on in-hospital mortality. The RV-Sm
      was lower in non-surviving (n = 27) than in the surviving (n = 28) and the
      control groups (n = 28) (P = .002). The RV-MPI was found to be higher in the non
      surviving patients than the surviving and the control groups (P < .001).
      CONCLUSION: Our study shows that the RV dysfunction evaluated using TDI,
      particularly the RV-Sm and MPI values, were related with the severity of sepsis
      and mortality.

PMID- 24011978
TI  - Editorial for "Diversity of the non-coding transcriptomes revealed by RNA-seq
      technologies".

PMID- 24011977
TI  - Circumscribed palmar or plantar hypokeratosis 10 years after the first
      description: what is known and the issues under discussion.
AB  - This review of the literature on palmoplantar hypokeratosis, a process that was
      first indentified only 10 years ago, discusses the current state of our
      understanding, the therapeutic options available, and the debate about etiology.
      Forty-four publications reporting 69 cases were found. Palmar or plantar
      hypokeratosis occurs mainly in women (76.8%) and age at the time of a first visit
      to a physician ranges from 42 to 84 years. Most cases present between the ages of
      51 and 70 years. The majority of patients have had solitary lesions usually
      located on the right palm, particularly in the regions of the thenar (in 44/79
      lesions [55.7%]) or hypothenar eminences (in 11/79 lesions [13.9%]). In only 8
      cases was there a history of prior trauma at the site. Studies using polymerase
      chain reaction techniques to identify human papillomavirus involvement were
      negative in most cases. These hypokeratotic lesions are localized epidermal
      depressions formed by an abrupt thinning of the stratum corneum, providing a
      singular histopathologic feature. This condition can currently be considered a
      localized keratinization disorder affecting zones where there is a thick stratum
      corneum. The precipitating cause is unknown and a definitive treatment remains to
      be found. The mechanism would be the localized failure of a clone of
      keratinocytes during differentiation toward normal palmoplantar
      hyperkeratinization.

PMID- 24011979
TI  - [Clinical and molecular diagnosis of facioscapulohumeral dystrophy type 1 (FSHD1)
      in 2012].
AB  - INTRODUCTION: Diagnosis of facioscapulohumeral dystrophy type 1 (FSHD1) is
      supported by a suggestive clinical presentation and associated with a
      heterozygous contraction of the D4Z4 repeat array on chromosome 4q35. STATE OF
      THE ART: The FSHD1 phenotype has a widely variable course with great inter- and
      intrafamilial heterogeneity. Three clinical forms can be distinguished: the
      classical phenotype associated with four to seven repeat units (RU) and a
      variable course, a severe infantile form with one to three RU, and a mild
      phenotype associated with borderline UR (8 to 10 RU). At the molecular level, for
      D4Z4 contraction to be pathogenic, it needs to occur on a specific chromosomal
      background, namely on the 4qA allelic variant of chromosome 4. In most cases,
      once FSHD is clinically suspected, the diagnosis can be genetically confirmed
      with a DNA test using Southern Blotting and hybridization to a set of probes.
      However, diagnosis of FSHD1 remains challenging. Firstly, some patients may
      present with an atypical phenotype with highly focal or unusual symptoms.
      Secondly, there are potential pitfalls in the genetic diagnosis of FSHD resulting
      in false positive or false negative results. In the absence of genetic
      confirmation, other investigations, mainly EMG and muscle biopsy, are needed to
      rule out another diagnosis. In cases with no clear diagnosis and a permissive
      chromosome without contraction, FSHD2 may be suspected. PERSPECTIVES: Molecular
      combing is a new technique which permits visualization and sizing of the D4Z4
      repeat array on its genetic background on stretched single DNA fibers by
      fluorescence microscopy. This tool will improve genetic diagnosis in FSHD
      patients. CONCLUSION: Diagnosis of FSHD1 is mainly supported by clinical
      features. Clinicians need to be aware of unusual presentations of this disease.
      The wide spectrum of intrafamilial variability and the lack of good correlation
      between genotype and phenotype present challenges for genetic counseling and
      prognostication. More studies are needed concerning penetrance and genotype
      phenotype correlation.

PMID- 24011980
TI  - Genetics of frontotemporal lobar degeneration: an up-date and diagnosis
      algorithm.
AB  - The last decade marked a turning point in the knowledge of frontotemporal lobar
      degenerations (FTLD). Major discoveries were made with the identification of TDP
      43 and FUS, two novel key players in FTLD. The growing number of FTLD genes has
      considerably changed our clinical practice. The high intrafamilial variability of
      phenotypes underlines the necessity of a careful interview concerning the family
      history, regarding FTLD diseases, but also other neurodegenerative and extra
      neurological disorders. Knowledge of the different genetic forms of FTLD and
      their associated phenotypes become essential to propose appropriate genetic
      diagnosis to the patients, and deliver accurate genetic counseling to their
      families. We propose an algorithm based on four criteria to help to pinpoint the
      genetic cause of FTLD: Presence of ALS in the patient or family; age at onset of
      FTLD; progranulin plasma level; and other disorders present in the patient or
      family. Presence of ALS is strongly indicative of a C9ORF72 expansion; a very
      early age at onset (<50 years), parkinsonism and oculomotor dysfunction are
      indicative of MAPT mutations; whereas hallucinations, CBDS and PNFA are
      indicative of PGRN mutations. A C9ORF72 repeat expansion should be searched for
      therefore in patients with FTLD-ALS, followed by sequencing of exon 6 of TARDBP
      gene in negative cases. Since C9ORF72 expansions are as frequent as PGRN
      mutations in patients with pure FTLD, both should be investigated, except in
      early familial FTLD (<50) where MAPT mutations should be searched for first. VCP,
      SQSTM1 and hnRNPA2B1 gene-sequencing could be proposed in patients or families
      presenting 'multisystem proteinopathy'. The genes currently identified explain 50
      60% of familial forms of FTLD. The identification of new FTLD genes involved
      remains a major challenge to gain further insight into the pathology and even
      better clarify the classification of FTLD in the future. 

PMID- 24011981
TI  - Restless legs syndrome associated with exercise intolerance: Data from a
      retrospective observational clinical neuromuscular center study.
AB  - INTRODUCTION: Exercise intolerance (EI) is a frequent motive for seeking
      neuromuscular consultation and may be a sign of metabolic disease or, rarely,
      muscular dystrophy. The diagnosis is not established in many patients with a
      typical clinical presentation. Nevertheless, some of them complain of sleep
      disorders and more especially of restless legs syndrome (RLS). OBJECTIVE: The
      objective of our study was to estimate the frequency of RLS in patients
      presenting with EI. METHODS: Our retrospective observational study included all
      patients seen in the center from 2005 to 2011, who were subsequently investigated
      for EI in the neuromuscular department of the Caen University hospital. Data were
      collected on clinical RLS and muscular investigations (creatine kinase [CK], EMG,
      maximal exercise tests magnetic resonance imaging [MRI] and muscle biopsy
      obtained along with muscle exploration). RESULTS: Of the 318 patient records
      analyzed, 84 showed patients accurately complaining of EI. RLS was diagnosed in
      25 of these patients (29.7%). This percentage was significantly higher (P<0.001)
      than found in the general population. Improvement was seen in 91.3% of the
      patients receiving specific treatment. CONCLUSION: RLS can sometimes present with
      pain, potentially worsening with exercise, inappropriately leading to a
      hypothesis of EI. Clinicians should thus explore the possible diagnosis of RLS
      when a muscular disease is not found in patients presenting with such symptoms.

PMID- 24011982
TI  - Magnetic resonance imaging for diagnosis of early Alzheimer's disease.
AB  - A major challenge for neuroimaging is to contribute to the early diagnosis of
      Alzheimer's disease (AD). In particular, magnetic resonance imaging (MRI) allows
      detecting different types of structural and functional abnormalities at an early
      stage of the disease. Anatomical MRI is the most widely used technique and
      provides local and global measures of atrophy. The recent diagnostic criteria of
      "mild cognitive impairment due to AD" include hippocampal atrophy, which is
      considered a marker of neuronal injury. Advanced image analysis techniques
      generate automatic and reproducible measures both in the hippocampus and
      throughout the whole brain. Recent modalities such as diffusion-tensor imaging
      and resting-state functional MRI provide additional measures that could
      contribute to the early diagnosis but require further validation. 

PMID- 24011983
TI  - ETNA3, a clinical randomized study assessing three cognitive-oriented therapies
      in dementia: rationale and general design.
AB  - Despite the popularity of cognitive-oriented therapies in dementia, very few data
      gathered from scientific literature provide a clear demonstration of the genuine
      efficacy of these techniques. Most of the results published have issued from
      studies suffering from important methodological limitations such as: absence of
      control group to compare clinical courses, very small size of study samples,
      absence of group randomization, absence of blind assessment of efficacy criteria
      or absence of long-term efficacy assessment. Randomized clinical trials are rare
      or even absent for some techniques and generally report more modest benefits. In
      this context, the ETNA3 study has been implemented. The ETNA3 study is a French
      nationwide prospective simple-blinded randomized clinical trial conducted to
      evaluate the impact of cognitive training, reminiscence therapy and an
      individualized cognitive rehabilitation program on the progression rate of
      dementia. The study was conducted in 653 outpatients with mild to moderate
      Alzheimer's disease followed up for 2 years (MMSE score 16 and 26). The main
      objective was to determine whether any or several of these non-pharmacological
      treatments could delay the severe stage of dementia during a 2-year follow-up
      compared to a usual care group without non-pharmacological treatment. The
      secondary outcomes assessed cognitive abilities, functional abilities in
      activities of daily living, behavioral disturbance, apathy, quality of life,
      depression, caregiver's burden and resource utilization. This article presents
      the rationale and methodology of the study.

PMID- 24011984
TI  - [Exercise-induced muscle pain due to phosphofrutokinase deficiency: Diagnostic
      contribution of metabolic explorations (exercise tests, 31P-nuclear magnetic
      resonance spectroscopy)].
AB  - INTRODUCTION: Muscle phosphofructokinase deficiency, the seventh member of the
      glycogen storage diseases family, is also called Tarui's disease (GSD VII).
      METHODS: We studied two patients in two unrelated families with Tarui's disease,
      analyzing clinical features, CK level, EMG, muscle biopsy findings and molecular
      genetics features. Metabolic muscle explorations (forearm ischemic exercise test
      [FIET]; bicycle ergometer exercise test [EE]; 31P-nuclear magnetic resonance
      spectroscopy of calf muscle [31P-NMR-S]) are performed as appropriate. RESULTS:
      Two patients, a 47-year-old man and a 38-year-old woman, complained of exercise
      induced fatigue since childhood. The neurological examination was normal or
      showed light weakness. Laboratory studies showed increased CPK, serum uric acid
      and reticulocyte count without anemia. There was no increase in the blood lactate
      level during the FIET or the EE although there was a light increase in the
      respiratory exchange ratio during the EE. 31P-NMR-S revealed no intracellular
      acidification or accumulated intermediates such as phosphorylated monoesters
      (PME) known to be pathognomic for GSD VII. Two new mutations were identified.
      DISCUSSION: FIET and EE were non-contributive to diagnosis, but 31P-NMR provided
      a characteristic spectra of Tarui's disease, in agreement with
      phosphofructokinase activity level in erythrocytes. Muscle biopsy does not always
      provide useful information for diagnosis. In these two cases, genetic studies
      failed to establish a genotype-phenotype correlation. CONCLUSION: The search for
      phosphofructokinase deficiency should be continued throughout life in adults
      experiencing fatigability or weakness because of the severe disability for daily
      life activities caused by the late onset form.

PMID- 24011985
TI  - Electroencephalographic features of benign adult familial myoclonic epilepsy.
AB  - OBJECTIVE: To investigate electroencephalographic (EEG) features of benign adult
      familial myoclonic epilepsy (BAFME). METHODS: We reviewed interictal EEG features
      in patients with BAFME treated between April 2005 and November 2012 at a tertiary
      referral center. The diagnostic criteria for BAFME were the presence of
      infrequent generalized tonic-clonic seizures, myoclonus or myoclonic seizures,
      and autosomal dominant inheritance. Interictal EEG findings of epilepsy with
      generalized tonic-clonic seizure only (EGTCS) were reviewed for comparison. We
      randomly selected 10 generalized spike/polyspike and wave complexes (GSW) for
      each BAFME patient and measured the duration of them. Photic stimulation and
      hyperventilation were performed in all. RESULTS: Nineteen (eight men, 11 women)
      patients with BAFME were included in this study. The mean frequency of GSW was
      4.3+/-1.0Hz (mean+/-SD, n=14) in BAFME and 3.2+/-0.8Hz (n=10) in EGTCS. There was
      a statistically significant difference (p=0.008) between the two. Photoparoxysmal
      responses (PPR) were noted in 18 (95%) patients with BAFME but 1 (10%) with
      EGTCS. CONCLUSION: Faster frequency of GSW, compared with that in EGTCS,
      accompanied by PPR may be characteristic EEG features of BAFME. SIGNIFICANCE:
      These findings may lead the diagnosis of BAFME.

PMID- 24011986
TI  - Effects of working memory load, a history of conduct disorder, and sex on
      decision making in substance dependent individuals.
AB  - BACKGROUND: Substance dependence and antisocial psychopathology, such as a
      history of childhood conduct disorder (HCCD), are associated with impulsive or
      disadvantageous decision making and reduced working memory capacity (WMC).
      Reducing WMC via a working memory load increases disadvantageous decision making
      in healthy adults, but no previous studies have examined this effect in young
      adults with substance dependence and HCCD. METHOD: Young adults with substance
      dependence (SubDep; n=158, 71 female), substance dependence and HCCD
      (SubDep+HCCD; n=72, 24 female), and control participants (n=152, 84 female)
      completed a test of decision making (the Iowa Gambling Task; IGT) with or without
      a concurrent working memory load intended to tax WMC. Outcomes were (i) net
      advantageous decisions on the IGT, and (ii) preferences for infrequent- versus
      frequent-punishment decks. RESULTS: SubDep+HCCD men made fewer advantageous
      decisions on the IGT than control men without a load, but there were no group
      differences among women in that condition. Load was associated with fewer
      advantageous decisions for SubDep+HCCD women and control men, but not for men or
      women in the other groups. Participants showed greater preference for infrequent
      punishment, advantageous decks under load as well. CONCLUSIONS: There are gender
      differences in the effects of substance dependence, HCCD, and working memory load
      on decision making on the IGT. Decision making by control men and SubDep+HCCD
      women suffered the most under load. Load increases preferences for less-frequent
      punishments, similar to a delay discounting effect. Future research should
      clarify the cognitive and neural mechanisms underlying these effects.

PMID- 24011987
TI  - Intravenous colistin in a patient with serious burns and borderline syndrome: the
      benefits of therapeutic drug monitoring.
AB  - Colistin is a decades-old drug that fell out of favour due to its nephrotoxicity.
      Today, colistin is experiencing a renaissance as a treatment against
      multiresistant Gram-negative bacteria such as Pseudomonas and Acinetobacter in
      critically ill patients. The optimal dosing of colistin for most infections is
      unknown. Here we present the intravenous dosing, optimised by therapeutic drug
      monitoring (TDM), of a borderline patient with severe burns and a consecutive
      transfemoral amputation. A 32-year-old woman with severe burns (35% total body
      surface area) and sepsis exhibited normal serum creatinine (SCr) concentrations
      at the beginning of her intensive care unit (ICU) stay, but over the course of
      her ICU stay her SCr increased to 100 MUmol/L. With the colistin standard dose of
      3 * 3 million units (MU) colistin/day after a loading dose of 9 MU, she failed to
      achieve effective plasma concentrations. The estimated glomerular filtration rate
      (eGFR) via CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) revealed
      GFRs between 180 mL/min and 63 mL/min after correcting for body surface. The
      patient required a high daily dosage of colistin (3 * 6 MU) that exceeded the
      approved maximum dose. Most clinicians rely heavily on SCr concentrations as the
      primary biochemical marker of GFR. At most, the CKD-EPI formula is helpful in
      determining creatinine clearance. The pharmacokinetics of colistin are currently
      poorly understood. TDM of colistin methanesulfonate and colistin may represent an
      invaluable approach to optimise colistin drug exposure in ICU patients with
      fluctuating renal clearance.

PMID- 24011988
TI  - An X-linked cobalamin disorder caused by mutations in transcriptional coregulator
      HCFC1.
AB  - Derivatives of vitamin B12 (cobalamin) are essential cofactors for enzymes
      required in intermediary metabolism. Defects in cobalamin metabolism lead to
      disorders characterized by the accumulation of methylmalonic acid and/or
      homocysteine in blood and urine. The most common inborn error of cobalamin
      metabolism, combined methylmalonic acidemia and hyperhomocysteinemia, cblC type,
      is caused by mutations in MMACHC. However, several individuals with presumed cblC
      based on cellular and biochemical analysis do not have mutations in MMACHC. We
      used exome sequencing to identify the genetic basis of an X-linked form of
      combined methylmalonic acidemia and hyperhomocysteinemia, designated cblX. A
      missense mutation in a global transcriptional coregulator, HCFC1, was identified
      in the index case. Additional male subjects were ascertained through two
      international diagnostic laboratories, and 13/17 had one of five distinct
      missense mutations affecting three highly conserved amino acids within the HCFC1
      kelch domain. A common phenotype of severe neurological symptoms including
      intractable epilepsy and profound neurocognitive impairment, along with variable
      biochemical manifestations, was observed in all affected subjects compared to
      individuals with early-onset cblC. The severe reduction in MMACHC mRNA and
      protein within subject fibroblast lines suggested a role for HCFC1 in
      transcriptional regulation of MMACHC, which was further supported by the
      identification of consensus HCFC1 binding sites in MMACHC. Furthermore, siRNA
      mediated knockdown of HCFC1 expression resulted in the coordinate downregulation
      of MMACHC mRNA. This X-linked disorder demonstrates a distinct disease mechanism
      by which transcriptional dysregulation leads to an inborn error of metabolism
      with a complex clinical phenotype. 

PMID- 24011989
TI  - Mutations in BCAP31 cause a severe X-linked phenotype with deafness, dystonia,
      and central hypomyelination and disorganize the Golgi apparatus.
AB  - BAP31 is one of the most abundant endoplasmic reticulum (ER) membrane proteins.
      It is a chaperone protein involved in several pathways, including ER-associated
      degradation, export of ER proteins to the Golgi apparatus, and programmed cell
      death. BAP31 is encoded by BCAP31, located in human Xq28 and highly expressed in
      neurons. We identified loss-of-function mutations in BCAP31 in seven individuals
      from three families. These persons suffered from motor and intellectual
      disabilities, dystonia, sensorineural deafness, and white-matter changes, which
      together define an X-linked syndrome. In the primary fibroblasts of affected
      individuals, we found that BCAP31 deficiency altered ER morphology and caused a
      disorganization of the Golgi apparatus in a significant proportion of cells.
      Contrary to what has been described with transient-RNA-interference experiments,
      we demonstrate that constitutive BCAP31 deficiency does not activate the unfolded
      protein response or cell-death effectors. Rather, our data demonstrate that the
      lack of BAP31 disturbs ER metabolism and impacts the Golgi apparatus,
      highlighting an important role for BAP31 in ER-to-Golgi crosstalk. These findings
      provide a molecular basis for a Mendelian syndrome and link intracellular protein
      trafficking to severe congenital brain dysfunction and deafness. 

PMID- 24011990
TI  - Polycyclic aromatic hydrocarbons (PAHs) in soils from a multi-industrial city,
      South Korea.
AB  - We collected soil samples at 25 sites in Ulsan, Korea to investigate the levels,
      patterns, spatial distribution, and sources of polycyclic aromatic hydrocarbons
      (PAHs) in the summer 2010. The target compounds were the 16 US-EPA priority PAHs.
      For the source identification of PAHs, diagnostic ratios and the positive matrix
      factorization (PMF) model were used. The total concentrations of PAHs ranged from
      65 ng/g to 12,000 ng/g (mean: 960 ng/g, median 330 ng/g). The levels and
      distribution of PAHs indicated that industrial areas were more polluted than
      rural and urban areas. The diagnostic ratios suggested that the soil samples were
      contaminated by pyrogenic sources and traffic emission. According to the result
      of PMF, four factors were identified: gasoline and heavy oil combustion (14%),
      diesel combustion (54%), coke oven (23%), and coal/biomass burning (9%).
      Therefore, it was concluded that vehicles and industrial complexes were major
      sources of PAHs in Ulsan.

PMID- 24011991
TI  - Comparative evaluation of serum levels of main minerals and postmenopausal
      osteoporosis.
AB  - OBJECTIVE: The purpose of this study was to determine the relationship between
      serum main minerals and postmenopausal osteoporosis. STUDY DESIGN: A total of 728
      postmenopausal women were included in this study. Women were separated into two
      groups according to presence or absence of osteoporosis (OP). BMD was measured in
      total femur (TF), femoral neck (FN) and lumbar spine (L1-L4) by dual-energy X-ray
      absorptiometry. Risk factors for OP were recorded by using a structured
      questionnaire. MAIN OUTCOME MEASURES: Women's blood were collected and serum
      concentrations of iron, copper, zinc, sodium, potassium, magnesium, calcium,
      ionized calcium, inorganic phosphorus were measured. RESULTS: Low serum copper
      levels were significantly associated with OP according to BMD values for TF, FN
      and L1-L4. There was a significant relationship between low serum zinc levels and
      OP for L1-L4 spines. Low iron serum levels were also significantly associated
      with OP in BMD measurements of TF. Low serum magnesium levels had significant
      association with OP of L1-L4 spines and TF. Serum levels of calcium, ionized
      calcium, potassium, sodium and inorganic phosphorus were not associated with OP.
      CONCLUSIONS: In postmenopausal women, the low serum levels of copper, zinc, iron
      and magnesium appear to be an important risk factor for OP.

PMID- 24011992
TI  - J wave syndromes: molecular and cellular mechanisms.
AB  - An early repolarization (ER) pattern in the ECG, consisting of J point elevation,
      distinct J wave with or without ST segment elevation or slurring of the terminal
      part of the QRS, was long considered a benign electrocardiographic manifestation.
      Experimental studies a dozen years ago suggested that an ER is not always benign,
      but may be associated with malignant arrhythmias. Validation of this hypothesis
      derives from recent case-control and population-based studies showing that an ER
      pattern in inferior or infero-lateral leads is associated with increased risk for
      life-threatening arrhythmias, termed early repolarization syndrome (ERS). Because
      accentuated J waves characterize both Brugada syndrome (BrS) and ERS, these
      syndromes have been grouped under the heading of J wave syndromes. BrS and ERS
      appear to share common ECG characteristics, clinical outcomes, risk factors as
      well as a common arrhythmic platform related to amplification of Ito-mediated J
      waves. However, they differ with respect to the magnitude and lead location of
      abnormal J waves and can be considered to represent a continuous spectrum of
      phenotypic expression. Recent studies support the hypothesis that BrS and ERS are
      caused by a preferential accentuation of the AP notch in right or left
      ventricular epicardium, respectively, and that this repolarization defect is
      accentuated by cholinergic agonists. Quinidine, cilostazol and isoproterenol
      exert ameliorative effects by reversing these repolarization abnormalities.
      Identifying subjects truly at risk is the challenge ahead. Our goal here is to
      review the clinical and genetic aspects as well as the cellular and molecular
      mechanisms underlying the J wave syndromes. 

PMID- 24011993
TI  - T-wave axis deviation and left ventricular hypertrophy interaction in diabetes
      and hypertension.
AB  - Electrocardiographic signs of left ventricular hypertrophy (ECG-LVH) and T-wave
      axis (TA) deviation are independent predictors of fatal and non fatal events. We
      assessed the prevalence of ECG-LVH, TA abnormalities and their combination
      according to the presence or absence of diabetes and/or hypertension in a large
      sample of the adult general Italian population. Data from 10,184 women (54 +/- 11
      years) and 8775 men (54 +/- 11 years) were analyzed from the Moli-sani cohort, a
      database of randomly recruited adults (age >35) from the general population of
      Molise, a central region of Italy that includes collection of standard 12-lead
      resting ECG. Subjects with previous myocardial infarction, angina,
      cerebrovascular disease or left bundle brunch block or missing values for TA or
      ECG-LVH have been excluded. TA was measured from the standard 12-lead ECG and it
      was defined as the rotation of the T wave in the frontal plane as computed by a
      proprietary algorithm (CalECG/Bravo, AMPS-LLC, NY). ECG-LVH was defined as
      Sokolow Lyon voltage (SLv) >35 mm or Cornell voltage duration Product (CP) >=
      2440 mm*ms. Among subjects with ECG-LVH, prevalence of hypertension was 59.0% and
      49.7%, respectively for men and women, whereas that of diabetes was 10.7% and
      5.7%. In hypertensives, TA was normal in 72.3% of subjects, borderline in 24.8%
      and abnormal in 2.9%. In diabetics, TA was normal in 70.4% of subjects,
      borderline in 26.5% and abnormal in 3.1%. In both hypertensive and diabetic
      subjects, the prevalence of ECG-LVH, was significantly greater in subjects with
      borderline or abnormal TA. Hypertension was an independent predictor of abnormal
      TA (odd ratio: 1.38, P = .025). These results suggest that hypertension might
      play a relevant role in the pathogenesis of TA deviation.

PMID- 24011994
TI  - Retinal detachment after open globe injury.
AB  - PURPOSE: To characterize the development of retinal detachment (RD) after open
      globe trauma. DESIGN: Case-control study. PARTICIPANTS: A total of 892 patients
      comprising 893 open globe injuries (OGIs), of whom 255 were ultimately diagnosed
      with RD, with the remaining eyes serving as controls. METHODS: Retrospective
      chart review of patients with OGIs presenting to the Massachusetts Eye and Ear
      Infirmary between 1999 and 2011. Kaplan-Meier analysis was used to estimate the
      time to detachment, and multivariable logistic regression was used to define the
      clinical factors associated with RD after OGI. MAIN OUTCOME MEASURES: Demographic
      and clinical characteristics at the time of presentation after OGI, date of RD
      diagnosis, and last date of follow-up. RESULTS: Primary repair of the open globe
      was typically undertaken within hours of presentation. A total of 255 eyes were
      ultimately diagnosed with RD after open globe trauma, yielding an incidence of
      29% (95% confidence interval, 26-32). For eyes that developed RD, 27% (69/255)
      detached within 24 hours of primary open globe repair, 47% (119/255) detached
      within 1 week, and 72% (183/255) detached within 1 month. Multivariable
      regression analysis revealed the presence of vitreous hemorrhage (odds ratio
      [OR], 7.29; P < 0.001), higher zone of injury (OR, 2.51 per integer increase in
      zone number; OR, 1.00-6.30; P < 0.001), and poorer logarithm of the minimum angle
      of resolution (logMAR) visual acuity at the time of presentation after OGI (OR,
      2.41 per integer increase in logMAR visual acuity; OR, 1.00-81.30; P < 0.001) to
      be associated with RD. A screening tool was created: the Retinal Detachment after
      Open Globe Injury score. CONCLUSIONS: Retinal detachment is common after open
      globe trauma, although often not appearing until days to weeks after the initial
      traumatic event. Several clinical variables at the time of initial presentation
      can predict the future risk of detachment.

PMID- 24011995
TI  - Infliximab for the treatment of refractory noninfectious Uveitis: a study of 88
      patients with long-term follow-up.
AB  - OBJECTIVE: To establish the safety and efficacy of infliximab for the treatment
      of refractory noninfectious uveitis. DESIGN: Retrospective, interventional,
      noncomparative cohort study. PARTICIPANTS: Eighty-eight patients from a single
      center private practice. METHODS: Patients with chronic, recalcitrant uveitis
      treated with infliximab (Remicade; Janssen Biotech, Inc., Titusville, NJ) were
      identified through an electronic medical record database. All charts were
      reviewed for sex, diagnosis, location of inflammation, presence of vasculitis,
      prior immunomodulatory treatments, duration of infliximab treatment, dose
      received, secondary side effects, and other medications continued while receiving
      treatment with infliximab. MAIN OUTCOME MEASURES: The primary outcome measures
      were the rate of remission, time to remission, relapse rate, failure rate, and
      patient tolerance. Additional analysis aimed to identity risk factors that would
      predict a higher success rate of infliximab to treat various types of
      noninfectious uveitis. RESULTS: Of the 72 patients (81.8%) who achieved clinical
      remission while being treated with infliximab, 42 (58.3%) required additional
      immunomodulatory medications. At 7, 18.1, and 44.7 weeks, 25%, 50%, and 75% of
      patients, respectively, achieved clinical remission off all corticosteroids.
      Thirty-two patients (36.4%) experienced at least 1 side effect while on
      infliximab therapy, and 17 patients (19.3%) discontinued treatment secondary to 1
      or more intolerable side effects. The most common adverse effects were skin rash
      (9.1%) and fatigue (8%). Factors associated with a higher chance to achieve
      clinical remission were nonidiopathic uveitis (P < 0.001), intermediate or
      panuveitis (P < 0.001), absence of vasculitis (P < 0.001), and a starting dose
      >=5 mg/kg (P < 0.011). CONCLUSIONS: Infliximab induces a high rate of complete
      clinical remission in recalcitrant uveitis and is well tolerated by most
      patients.

PMID- 24011996
TI  - Structural and energetic analysis of drug inhibition of the influenza A M2 proton
      channel.
AB  - The type A influenza virus matrix protein 2 (M2) is a highly selective proton
      channel in the viral envelope. Because of its crucial role in viral infection and
      replication, the M2 channel has been a target of anti-influenza drugs. Due to the
      occurrence of drug-resistant mutations in the M2 channel, existing anti-influenza
      drugs that block the M2 channel, such as amantadine and rimantadine, have lost
      their efficacy against these mutant channels. Recent experimental and
      computational efforts have made great progress in understanding the drug
      resistance mechanisms of these mutations as well as designing novel drug
      candidates to block the mutant M2 channels. In this review, we briefly summarize
      the structural characteristics of the M2 channel, and then we discuss these
      recent studies on drug resistance and drug design of the mutant channels,
      focusing on the structures and energetics. We show that structural biology
      experiments and molecular modeling have led to the successful design of novel
      drugs targeting mutant M2 channels. 

PMID- 24011997
TI  - The many layers of specification and plasticity in the neocortex.
AB  - In this issue of Neuron, Li et al. (2013) show that transgenically eliminating
      thalamocortical neurotransmission disrupts the formation of barrel columns in the
      somatosensory cortex and cortical lamination, providing evidence for the
      importance of extrinsic activity-dependent factors in cortical development. 

PMID- 24011998
TI  - Dopamine: burning the candle at both ends.
AB  - Dopamine neurons are well known for signaling reward-prediction errors. In this
      issue, Matsumoto and Takada (2013) show that some dopamine neurons also signal
      salient events during progression through a visual search task requiring working
      memory and sustained attention. 

PMID- 24011999
TI  - The cerebral emporium of benevolent knowledge.
AB  - Visual objects tend to be found in predictable combinations (e.g., pens with
      paper). How does the brain represent these regularities? In this issue of Neuron,
      Stansbury et al. (2013) use fMRI to study the brain's representation of visual
      scene categories. 

PMID- 24012000
TI  - Theory of mind: a neural prediction problem.
AB  - Predictive coding posits that neural systems make forward-looking predictions
      about incoming information. Neural signals contain information not about the
      currently perceived stimulus, but about the difference between the observed and
      the predicted stimulus. We propose to extend the predictive coding framework from
      high-level sensory processing to the more abstract domain of theory of mind; that
      is, to inferences about others' goals, thoughts, and personalities. We review
      evidence that, across brain regions, neural responses to depictions of human
      behavior, from biological motion to trait descriptions, exhibit a key signature
      of predictive coding: reduced activity to predictable stimuli. We discuss how
      future experiments could distinguish predictive coding from alternative
      explanations of this response profile. This framework may provide an important
      new window on the neural computations underlying theory of mind. 

PMID- 24012001
TI  - Integration of GABAergic interneurons into cortical cell assemblies: lessons from
      embryos and adults.
AB  - In the forebrain, cortical structures consist of networks of excitatory and
      inhibitory neurons born in distant locations. Understanding how these two major
      classes of neurons integrate into unique functional cell assemblies may shed
      light on the organization of cortical circuits. In this review, we provide an
      overview of the mechanisms used by GABAergic interneurons to reach their final
      position, with an emphasis on the final steps of this process. To this end, we
      analyze similarities and differences between the integration of GABAergic
      interneurons in the developing cerebral cortex and in the postnatal brain, using
      the neocortex and the olfactory bulb as model systems. 

PMID- 24012002
TI  - Microglial beclin 1 regulates retromer trafficking and phagocytosis and is
      impaired in Alzheimer's disease.
AB  - Phagocytosis controls CNS homeostasis by facilitating the removal of unwanted
      cellular debris. Accordingly, impairments in different receptors or proteins
      involved in phagocytosis result in enhanced inflammation and neurodegeneration.
      While various studies have identified extrinsic factors that modulate
      phagocytosis in health and disease, key intracellular regulators are less
      understood. Here we show that the autophagy protein beclin 1 is required for
      efficient phagocytosis in vitro and in mouse brains. Furthermore, we show that
      beclin 1-mediated impairments in phagocytosis are associated with dysfunctional
      recruitment of retromer to phagosomal membranes, reduced retromer levels, and
      impaired recycling of phagocytic receptors CD36 and Trem2. Interestingly,
      microglia isolated from human Alzheimer's disease (AD) brains show significantly
      reduced beclin 1 and retromer protein levels. These findings position beclin 1 as
      a link between autophagy, retromer trafficking, and receptor-mediated
      phagocytosis and provide insight into mechanisms by which phagocytosis is
      regulated and how it may become impaired in AD. 

PMID- 24012003
TI  - Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer abeta oligomer
      bound to cellular prion protein.
AB  - Soluble amyloid-beta oligomers (Abetao) trigger Alzheimer's disease (AD)
      pathophysiology and bind with high affinity to cellular prion protein (PrP(C)).
      At the postsynaptic density (PSD), extracellular Abetao bound to lipid-anchored
      PrP(C) activates intracellular Fyn kinase to disrupt synapses. Here, we screened
      transmembrane PSD proteins heterologously for the ability to couple Abetao-PrP(C)
      with Fyn. Only coexpression of the metabotropic glutamate receptor, mGluR5,
      allowed PrP(C)-bound Abetao to activate Fyn. PrP(C) and mGluR5 interact
      physically, and cytoplasmic Fyn forms a complex with mGluR5. Abetao-PrP(C)
      generates mGluR5-mediated increases of intracellular calcium in Xenopus oocytes
      and in neurons, and the latter is also driven by human AD brain extracts. In
      addition, signaling by Abetao-PrP(C)-mGluR5 complexes mediates eEF2
      phosphorylation and dendritic spine loss. For mice expressing familial AD
      transgenes, mGluR5 antagonism reverses deficits in learning, memory, and synapse
      density. Thus, Abetao-PrP(C) complexes at the neuronal surface activate mGluR5 to
      disrupt neuronal function. 

PMID- 24012004
TI  - The EBAX-type Cullin-RING E3 ligase and Hsp90 guard the protein quality of the
      SAX-3/Robo receptor in developing neurons.
AB  - Although protein quality control (PQC) is generally perceived as important for
      the development of the nervous system, the specific mechanisms of neuronal PQC
      have remained poorly understood. Here, we report that C. elegans Elongin BC
      binding axon regulator (EBAX-1), a conserved BC-box protein, regulates axon
      guidance through PQC of the SAX-3/Robo receptor. EBAX-1 buffers guidance errors
      against temperature variations. As a substrate-recognition subunit in the Elongin
      BC-containing Cullin-RING ubiquitin ligase (CRL), EBAX-1 also binds to DAF-21, a
      cytosolic Hsp90 chaperone. The EBAX-type CRL and DAF-21 collaboratively regulate
      SAX-3-mediated axon pathfinding. Biochemical and imaging assays indicate that
      EBAX-1 specifically recognizes misfolded SAX-3 and promotes its degradation in
      vitro and in vivo. Importantly, vertebrate EBAX also shows substrate preference
      toward aberrant Robo3 implicated in horizontal gaze palsy with progressive
      scoliosis (HGPPS). Together, our findings demonstrate a triage PQC mechanism
      mediated by the EBAX-type CRL and DAF-21/Hsp90 that maintains the accuracy of
      neuronal wiring. 

PMID- 24012005
TI  - GABAergic projection neurons route selective olfactory inputs to specific higher
      order neurons.
AB  - We characterize an inhibitory circuit motif in the Drosophila olfactory system,
      parallel inhibition, which differs from feedforward or feedback inhibition.
      Excitatory and GABAergic inhibitory projection neurons (ePNs and iPNs) each
      receive input from antennal lobe glomeruli and send parallel output to the
      lateral horn, a higher center implicated in regulating innate olfactory behavior.
      Ca(2+) imaging of specific lateral horn neurons as an olfactory readout revealed
      that iPNs selectively suppressed food-related odor responses, but spared signal
      transmission from pheromone channels. Coapplying food odorant did not affect
      pheromone signal transmission, suggesting that the differential effects likely
      result from connection specificity of iPNs, rather than a generalized inhibitory
      tone. Ca(2+) responses in the ePN axon terminals show no detectable suppression
      by iPNs, arguing against presynaptic inhibition as a primary mechanism. The
      parallel inhibition motif may provide specificity in inhibition to funnel
      specific olfactory information, such as food and pheromone, into distinct
      downstream circuits. 

PMID- 24012006
TI  - Odor discrimination in Drosophila: from neural population codes to behavior.
AB  - Taking advantage of the well-characterized olfactory system of Drosophila, we
      derive a simple quantitative relationship between patterns of odorant receptor
      activation, the resulting internal representations of odors, and odor
      discrimination. Second-order excitatory and inhibitory projection neurons (ePNs
      and iPNs) convey olfactory information to the lateral horn, a brain region
      implicated in innate odor-driven behaviors. We show that the distance between ePN
      activity patterns is the main determinant of a fly's spontaneous discrimination
      behavior. Manipulations that silence subsets of ePNs have graded behavioral
      consequences, and effect sizes are predicted by changes in ePN distances. ePN
      distances predict only innate, not learned, behavior because the latter engages
      the mushroom body, which enables differentiated responses to even very similar
      odors. Inhibition from iPNs, which scales with olfactory stimulus strength,
      enhances innate discrimination of closely related odors, by imposing a high-pass
      filter on transmitter release from ePN terminals that increases the distance
      between odor representations. 

PMID- 24012007
TI  - Different kenyon cell populations drive learned approach and avoidance in
      Drosophila.
AB  - In Drosophila, anatomically discrete dopamine neurons that innervate distinct
      zones of the mushroom body (MB) assign opposing valence to odors during olfactory
      learning. Subsets of MB neurons have temporally unique roles in memory
      processing, but valence-related organization has not been demonstrated. We
      functionally subdivided the alphabeta neurons, revealing a value-specific role
      for the ~160 alphabeta core (alphabetac) neurons. Blocking neurotransmission from
      alphabeta surface (alphabetas) neurons revealed a requirement during retrieval of
      aversive and appetitive memory, whereas blocking alphabetac only impaired
      appetitive memory. The alphabetac were also required to express memory in a
      differential aversive paradigm demonstrating a role in relative valuation and
      approach behavior. Strikingly, both reinforcing dopamine neurons and efferent
      pathways differentially innervate alphabetac and alphabetas in the MB lobes. We
      propose that conditioned approach requires pooling synaptic outputs from across
      the alphabeta ensemble but only from the alphabetas for conditioned aversion. 

PMID- 24012008
TI  - Molecular and functional asymmetry at a vertebrate electrical synapse.
AB  - Electrical synapses are abundant in the vertebrate brain, but their functional
      and molecular complexities are still poorly understood. We report here that
      electrical synapses between auditory afferents and goldfish Mauthner cells are
      constructed by apposition of hemichannels formed by two homologs of mammalian
      connexin 36 (Cx36) and that, while Cx35 is restricted to presynaptic hemiplaques,
      Cx34.7 is restricted to postsynaptic hemiplaques, forming heterotypic junctions.
      This molecular asymmetry is associated with rectification of electrical
      transmission that may act to promote cooperativity between auditory afferents.
      Our data suggest that, in similarity to pre- and postsynaptic sites at chemical
      synapses, one side in electrical synapses should not necessarily be considered
      the mirror image of the other. While asymmetry based on the presence of two Cx36
      homologs is restricted to teleost fish, it might also be based on differences in
      posttranslational modifications of individual connexins or in the complement of
      gap junction-associated proteins. 

PMID- 24012009
TI  - Laminar and columnar development of barrel cortex relies on thalamocortical
      neurotransmission.
AB  - A dynamic interplay between intrinsic regional molecular cues and extrinsic
      factors from the thalamus shape multiple features of early cortical development.
      It remains uncertain and controversial, however, whether the initial formation of
      cortical columns depends on neuronal activity, and there is little evidence that
      cortical lamination or neuronal differentiation is influenced by extrinsic
      activity. We examined the role of thalamic-derived factors in cortical
      development by selectively eliminating glutamatergic synaptic transmission from
      thalamocortical neurons in mice and found that eliminating thalamocortical
      neurotransmission prevented the formation of "barrel" columns in somatosensory
      cortex. Interestingly, based on cytoarchitectonic criteria and genetic markers,
      blocking thalamocortical neurotransmission also perturbed the development of
      superficial cortical lamina and the morphologic development of neurons. These
      experiments demonstrate that barrels and aspects of the layer-dependent pattern
      of cortical cytoarchitecture, gene expression, and neuronal differentiation
      depend on thalamocortical neurotransmission, extending the apparent influence of
      extrinsic, presumably activity-dependent factors, on cortical development.

PMID- 24012010
TI  - A modeling framework for deriving the structural and functional architecture of a
      short-term memory microcircuit.
AB  - Although many studies have identified neural correlates of memory, relatively
      little is known about the circuit properties connecting single-neuron physiology
      to behavior. Here we developed a modeling framework to bridge this gap and
      identify circuit interactions capable of maintaining short-term memory. Unlike
      typical studies that construct a phenomenological model and test whether it
      reproduces select aspects of neuronal data, we directly fit the synaptic
      connectivity of an oculomotor memory circuit to a broad range of anatomical,
      electrophysiological, and behavioral data. Simultaneous fits to all data,
      combined with sensitivity analyses, revealed complementary roles of synaptic and
      neuronal recruitment thresholds in providing the nonlinear interactions required
      to generate the observed circuit behavior. This work provides a methodology for
      identifying the cellular and synaptic mechanisms underlying short-term memory and
      demonstrates how the anatomical structure of a circuit may belie its functional
      organization. 

PMID- 24012011
TI  - Clinical equipoise in idiopathic normal pressure hydrocephalus: a survey of
      physicians on the need for randomized controlled trials assessing the efficacy of
      cerebrospinal fluid diversion.
AB  - BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a syndrome that
      may be reversible by diversion of cerebrospinal fluid (CSF). It is increasingly
      recognized, and accordingly rates of CSF diversion are increasing despite the
      absence of level I evidence of efficacy, non-neglible rate of complications and
      an unclear natural history. METHODS: A total of 349 neurosurgeons, neurologists,
      geriatricians and neuropsychiatrists rated the perceived efficacy of CSF
      diversion, the duration of effect of CSF diversion, and the risk-benefit ratio of
      CSF diversion in iNPH. These physicians then rated the need for a randomized
      controlled trial (RCT) of CSF diversion in iNPH. Participants detailed their
      desired selection criteria and supportive testing for a RCT, and their preferred
      control group. RESULTS: Physicians believe that there is uncertain efficacy of
      CSF diversion in iNPH, as well as the expected duration of this benefit and the
      risk-benefit ratio for patients. The greatest degree of uncertainty related to
      the long-term benefit of surgery. Accordingly, over 75% desire a RCT to determine
      the efficacy of CSF diversion in iNPH. Only 2.7% of participants believe a RCT of
      CSF diversion in iNPH is unethical. Patients without a shunt and a programmable
      valve in the 'off' setting were the preferred control groups. CONCLUSION: A RCT
      of CSF diversion in iNPH is absent from the literature. The majority (>75%) of
      physicians involved in the diagnosis and treatment of iNPH believe a RCT is
      required to determine the efficacy, duration of efficacy and risk-benefit ratio
      of CSF diversion in iNPH.

PMID- 24012012
TI  - Investigating the potential for evidence-based midwifery-led services in very
      remote Australia: viewpoints from local stakeholders.
AB  - BACKGROUND: Since the National Maternity Services Review, non-medical models of
      care involving midwives as the primary care giver are gaining prominence in urban
      settings in Australia. However, there remains a paucity of evidence about which
      non-medical primary maternity care models are best suited for rural and remote
      communities. AIM: We investigated the perceptions, acceptability and barriers and
      enablers to the delivery of non-medical primary maternity care models in Far West
      NSW, as an example of remote Australia. METHODS: We purposively sampled and
      invited 24 clinicians and/or policy makers to an in-depth interview via the phone
      or face-to-face. Quantitative items were coded and analysed descriptively,
      whereas qualitative responses were analysed for thematic content via two
      independent authors. RESULTS: Of 16 eligible participants, 14 consented to
      participate and were very experienced practitioners from a range of roles and
      settings. There was strong agreement that evidence supporting non-medical models
      of care was relevant to the remote context in Far West NSW. Participants reported
      that pregnant women and health service partners would find midwifery-led care
      very acceptable and that team models would be the easiest to deliver in their
      setting. Reported barriers and enablers for the delivery of midwifery-led care
      conversely reflected each other and emphasised the need for retention of local
      maternity staff to provide continuity of care. CONCLUSIONS: Local health service
      partners are demonstrably ready for further local improvement in providing
      midwifery-led models of maternity care to women who live in very remote
      communities in NSW, Australia.

PMID- 24012013
TI  - Femoral artery pseudoaneurysm due to Candida albicans in an injection drug user.
AB  - Candida arteritis is an uncommon condition but important to recognize due to the
      risk of significant morbidity and the difficulty in management of the enduring
      fungal infection. The authors report a rare case of a man with a femoral artery
      pseudoaneurysm with persistent Candida albicans infection, as a complication of
      infective endocarditis. The 23-year-old man, with a history of chronic
      intravenous drug use and Type I diabetes mellitus, presented with left groin
      pain, paresthesia of his left foot, and a pulsatile mass in the inguinal region.
      On imaging, he was found to have a pseudoaneurysm of the left common femoral
      artery, which later ruptured. Further investigation revealed vegetations on the
      mitral and aortic valves as well. Initial blood cultures were negative. He
      underwent multiple surgical interventions including replacement of the mitral and
      aortic valves and resection of the left common femoral artery with autogenous
      revascularization. In addition, he was commenced on intravenous antifungal
      therapy. Postoperatively, he continued to experience significant pain in the left
      groin and had two episodes of rerupture of the femoral artery that was
      consequently surgically repaired. Histological examination of the resected valves
      revealed vegetations with a mixture of fungal elements and bacterial cocci. The
      femoral artery resection specimens revealed evidence of infectious arteritis and
      the presence and persistence of C. albicans organisms in subsequent specimens.
      This case highlights the importance of an accurate diagnosis and aggressive
      management of fungal mycotic aneurysms in at-risk populations. 

PMID- 24012014
TI  - Long-term prospective teaching effectivity of practical skills training and a
      first OSCE in cranio maxillofacial surgery for dental students.
AB  - Basic skills in oral/CMF surgery should be taught effectively to dental students
      as surgical skills training is traditionally under-represented in the dental
      curriculum compared to its later need in daily clinical practice. Rigid
      curricular time frames and prospectively condensed professional education foster
      new effective teaching and examination formats. Transmitting and assessing
      clinical competence objectively (independent of subjective bias), reliably
      (repeatable, inter-rater consistency) and valid (representative, structured task
      selection) was intended and evaluated in oral/CMF surgery skills acquisition
      starting in summer 2009. A small-group practical skills training (PST) day
      initiated a one-week practical training course, covering previously formulated
      learning objectives. An objective structured clinical evaluation (OSCE) was held
      at the end of each semester. Theoretical background knowledge and clinical skills
      should have to be memorized within a representative number of practical tasks
      (test stations). A first semester (26 students) used classical practical training
      alone as controls, the following semesters (171 students) had PST, considered as
      a study group. All 197 students were assessed with OSCE's over a 3-year period.
      An instructor held PST based on presentations, videos and practical training,
      including mannequins, with pairs of students. This included history taking,
      communication and interpretation of laboratory/image diagnostics, structured
      clinical facial examination, fracture diagnosis, venipuncture, suturing, biopsy
      and wire loops on pig jaws for manual and clinical skills, which were later
      incorporated in OSCE stations. OSCE average results increased from 63.3 +/- 9.7%
      before and to 75.5 +/- 10% after the inclusion of PST (p < 0.05). Knowledge
      diffusion between sittings on the same test date and between consecutive
      semesters was insignificant. Students and faculty rated their learning/teaching
      experience "very good" to "good". PST was effective in optimizing clinical skills
      as evaluated by OSCE. 

PMID- 24012015
TI  - A comparative study of internal fixation and intermaxillary fixation on bone
      repair of mandibular fractures through radiographic subtraction.
AB  - Conventional radiographic evaluation of fracture healing is not a reliable
      method, because it depends on the examinator's experience and the quality of the
      exam. Therefore, serial images differing in density, contrast and geometrical
      projection can lead to a misdiagnosis on the postoperative fracture healing. Even
      in good quality images, little changes in calcified tissues often can't be
      visualized, because of its little sensibility and because of the limited human
      sight. The use of more sensitive and objective methods could increase the
      accuracy of this evaluation. This study intended to compare, by digitalized
      panoramic radiography, the mandible fracture healing after two different types of
      treatment: open reduction with internal fixation (group 1) and closed reduction
      with intermaxillary fixation (group 2). It was taken three postoperative
      radiographs (within a week, a month and three months after treatment), which were
      digitalized (600 dpi, 8 bits) and adjusted in brightness and size in Photoshop
      software. Then these images were evaluated by digital subtraction in ImageTool
      software. The results revealed greater areas of new bone formation in the
      internal fixation group, in all the evaluated times. Thus, open reduction with
      internal fixation resulted in more rapid fracture healing than closed reduction
      with intermaxillary fixation.

PMID- 24012016
TI  - Tablet computers in support of rural and frontier clinical practice.
AB  - PURPOSE: Healthcare organizations are increasingly faced with an environment in
      which they must implement health information systems to achieve higher standards
      for efficiency and quality of care while at the same time being asked to provide
      needed services with fewer resources. This is particularly challenging for rural
      health systems where access to resources is often more limited. This study
      investigates the potential value of iPad tablets for enhancing health services
      delivery by primary care physicians in rural Nevada. METHODS: Five physicians
      from rural Nevada were selected to receive iPads and funding for apps that would
      enhance their medical practices. Following a year of use, data was gathered on
      each physician's actual use and perceived value of the iPads. A case study
      approach was taken using both an online survey and semi-structured phone
      interviews to collect case data. RESULTS: Use and perceived usefulness of the
      iPad was mixed but generally positive with some physicians utilizing it much more
      than others. The iPads were primarily used by the physicians to access medical
      information through online resources (e.g. Epocrates and UpToDate) for reference
      and diagnostic purposes, although they were also used for some interaction with
      patients. All felt that resources available through the iPad were limited and
      that better applications would improve the usefulness of the iPad, particularly
      in regard to graphical and video content suitable to sharing with patients.
      CONCLUSIONS: Physicians in this study felt that the iPad could fill a need
      between smartphones and desktops, which were their primary technology tools prior
      to receiving the iPad, but that useful medical applications and resources are
      currently limited for the iPad. In particular, better graphical and video content
      would improve the usefulness of the iPad as a tool for patient interactions. Apps
      that store content locally would serve to mitigate inconsistent internet access
      that is still common in rural settings, increasing the usefulness of the iPad in
      that context. Tablets like the iPad also have potential for use in accessing the
      electronic medical record systems that are increasingly being implemented in
      rural hospitals and healthcare facilities.

PMID- 24012017
TI  - Redox-state sensing by hydrogen bonds in the CuA center of cytochrome c oxidase.
AB  - Cytochrome c oxidases (CcO) couple electron transfer to active proton
      translocation through a gated mechanism that minimizes energy losses by
      preventing protons from flowing backwards or leaking. Such a complex mechanism
      requires that information about the redox and protonation states of the different
      centers be transmitted between different parts of the oxidase. Here we report a
      network of residues located around the electron entry point of CcO, the CuA site
      in subunit II, that experience collective pH equilibria around neutral pH. This
      network starts at the occluded side of the CuA site and extends to the interface
      between subunits I and II of the CcO, where the proton exit is located and
      through which electrons flow into subunit I. One of the residues in this network
      is directly involved in a hydrogen bond to one of the CuA ligands, whose strength
      is highly sensitive to the redox state of the metal center. We propose that this
      interaction mediates the transmission of redox changes from ET centers to other
      functional regions of the oxidase, and possibly also in other similar
      machineries, as part of their gating and regulatory mechanisms. 

PMID- 24012018
TI  - Promoting access: the use of maternity waiting homes to achieve safe motherhood.
AB  - OBJECTIVE: to examine the structural and sociocultural factors influencing
      maternity waiting home (MWH) use through the lens of women, families, and
      communities in one rural county in postconflict Liberia. DESIGN: an exploratory,
      qualitative descriptive design using focus groups and in-depth, individual
      interviews was employed. Content analysis of data was performed using Penchansky
      and Thomas's (1981) five A's of access as a guiding framework. SETTING: rural
      communities in north-central Liberia. PARTICIPANTS: a convenience sampling was
      used to recruit participants. Eight focus groups were held with 75 participants
      from congruent groups of (1) MWH users, (2) MWH non-users, (3) family members of
      MWH users, and (4) family members of MWH non-users. Eleven individual interviews
      were conducted with clinic staff or community leaders. FINDINGS: the availability
      of MWHs decreased the barrier of distance for women to access skilled care around
      the time of childbirth. Food insecurity while staying at a MWH was identified as
      a potential barrier by participants. KEY CONCLUSIONS: examining access as a
      general concept within the specific dimensions of availability, accessibility,
      accommodation, affordability, and acceptability provides a way to describe the
      structural and sociocultural factors that influence access to a MWH and skilled
      attendance for birth. IMPLICATIONS FOR PRACTICE: MWHs can address the barrier of
      distance in accessing skilled care for childbirth in a rural setting with long
      distances to a facility.

PMID- 24012019
TI  - Intravenous iron sucrose for restless legs syndrome in pregnant women with low
      serum ferritin.
AB  - We report on two pregnant women who either had de novo restless legs syndrome
      (RLS) or had marked enhancement of preexisting RLS symptoms during pregnancy.
      Both patients had ferritin values <50 MUg/L at baseline. The patients had
      relevant sleep disorders and daytime symptoms caused by RLS. The women were
      treated in an open paradigm with intravenous iron sucrose. A few weeks after
      therapy, both patients experienced a significant reduction or even remission of
      RLS symptoms. Their quality of life and sleep substantially improved and no
      treatment-related adverse effects were observed. According to our initial
      experience, intravenous iron sucrose administration appears to be an effective
      therapy in RLS patients with low ferritin values during pregnancy.

PMID- 24012020
TI  - Spinocerebellar Ataxia (SCA) type 2 presenting with chorea.

PMID- 24012022
TI  - Medicolegal characteristics of cardiac catheterization litigation in the United
      States, 1985 to 2009.
AB  - There are few assessments of patterns of medicolegal cases involving cardiac
      catheterizations. This descriptive study reviews the patterns of liability and
      medical outcomes involving cardiac catheterization litigation from the LexisNexis
      Academic database and the Physician Insurers Association of America registry.
      From 1985 to 2009, the Physician Insurers Association of America registry
      documented 1,361 closed coronary angiography claims. The cardiovascular disease
      specialty was involved in 699 with other specialties involved in the remaining
      cases. Of the 1,361 closed claims, 301 (22%) resulted in payments to the
      plaintiff (average indemnity of $230,987). The most common alleged error was for
      improper performance (35.4%; average indemnity of $255,542). The alleged error
      with the highest average indemnity of $270,916 was errors in diagnosis. Not
      performing an indicated procedure had the highest ratio of paid to closed claims
      (41%) with an average indemnity of $246,988. In regard to the severity of injury,
      death was the most common outcome (44%). The highest ratio of paid to total
      closed claims (43%) was for grave injuries (highest average indemnity of
      $555,625). Of the 116 LexisNexis cases, litigation against physicians occurred in
      90.5% of cases with judgments in favor of the patients in 29.5%. When death was
      the outcome (31% of cases), physicians were highly likely to be sued (97%) and
      the judgment was more likely in the plaintiffs' favor (44%). In conclusion, in
      litigation related to cardiac catheterizations, most cases are due to medical
      malpractice and physicians are sued in a high percentage of cases. Cardiologists
      should recognize these patterns of litigation as these may impact and improve
      processes of care. 

PMID- 24012021
TI  - Alternating electric fields combined with activated carbon for disinfection of
      Gram negative and Gram positive bacteria in fluidized bed electrode system.
AB  - Strong electric fields for disinfection of wastewaters have been employed already
      for several decades. An innovative approach combining low strength (7 V/cm)
      alternating electric fields with a granular activated carbon fluidized bed
      electrode (FBE) for disinfection was presented recently. For disinfection
      performance of FBE several pure microbial cultures were tested: Bacillus
      subtilis, Bacillus subtilis subsp. subtilis, Enterococcus faecalis as
      representatives from Gram positive bacteria and Erwinia carotovora, Pseudomonas
      luteola, Pseudomonas fluorescens and Escherichia coli YMc10 as representatives
      from Gram negative bacteria. The alternating electric field amplitude and shape
      were kept constant. Only the effect of alternating electric field frequency on
      disinfection performance was investigated. From the bacteria tested, the Gram
      negative strains were more susceptible and the Gram positive microorganisms were
      more resistant to FBE disinfection. The collected data indicate that the
      efficiency of disinfection is frequency and strain dependent. During 6 h of
      disinfection, the decrease above 2 Log units was achieved with P. luteola and E.
      coli at 10 kHz and at dual frequency shift keying (FSK) modulated signal with
      frequencies of 10 kHz and 140 kHz. FBE technology appears to offer a new way for
      selective bacterial disinfection, however further optimizations are needed on
      treatment duration, and energy input, to improve effectiveness.

PMID- 24012023
TI  - Prevalence of symptomatic congenital heart disease in Tibetan school children.
AB  - The prevalence of congenital heart disease (CHD) in Tibet has not been fully
      investigated. The aim of this study was to illustrate and compare the prevalence
      of symptomatic CHD and its major subtypes in Tibetan children at different
      altitudes. A total of 5,790 children from regions at altitudes of 3,500 to 4,100
      m (group L) and 4,548 children from 4,200 to 4,900 m (group H) were compared for
      CHD prevalence. Group H had greater prevalence of total CHD (12.09 vs 4.32 per
      1,000, p <0.001), patent ductus arteriosus (PDA, 7.70 vs 1.38 per 1,000, p
      <0.001), and atrial septal defect (ASD, 3.52 vs 2.25 per 1,000, p = 0.23) than
      group L. The differences were more remarkable in women (CHD, 18.63 vs 4.88 per
      1,000, p <0.001; PDA, 11.53 vs 1.74 per 1,000, p <0.001; ASD, 5.32 vs 2.79 per
      1,000, p = 0.15). No significant difference was observed in the prevalence of
      ventricular septal defect between the 2 groups (0.44 vs 0.35 per 1,000, p >0.05).
      The most common cardiac defect was ASD (52.0%) in group L compared with PDA
      (63.6%) in group H. In group L, women had slightly and insignificantly greater
      prevalence of total CHD, PDA, and ASD than men. In contrast, the prevalence was
      almost threefold greater in women than men in group H. In conclusion, the CHD
      prevalence and composition differed significantly between populations of school
      children living above and below 4,200 m.

PMID- 24012024
TI  - Usefulness of updated valve academic research consortium-2 criteria for acute
      kidney injury following transcatheter aortic valve implantation.
AB  - Acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI) is
      frequent and associated with adverse outcomes. We aimed to identify the incidence
      and risk factors for AKI after TAVI using the updated Valve Academic Research
      Consortium-2 classification criteria. We performed a retrospective analysis of
      300 consecutive patients undergoing TAVI using either Edwards SAPIEN XT or
      CoreValve bioprostheses at our medical center. Change in serum creatinine from
      base line to 48 to 72 hours after TAVI was used to define AKI stages 1 to 3. The
      final study cohort included 251 patients. Overall incidence of AKI was 16.7% (42
      of 251); of which, stage 1 AKI was 15.1% (38 of 251), stage 2 AKI was 1.6% (4 of
      251), and none had stage 3 AKI or required hemodialysis. All-cause mortality at
      30 days and 1 year was greater among patients with AKI (9.5% vs 1%, p <0.01% and
      25.7% vs 12.3%, p = 0.041, respectively). Despite greater volume of contrast
      media used in Edwards SAPIEN versus CoreValve (162 ml vs 142 ml, p = 0.02), there
      was no difference in the incidence of AKI between the 2 valve types (23.7% vs
      15.5%, p = 0.238) or when comparing larger (29 to 31 mm) versus smaller size
      valves (23 to 26 mm; 17.7% vs 16.1%, p = 0.745). AKI was associated with chronic
      kidney disease, history of peripheral vascular disease, blood transfusion, and
      higher EuroSCORE (p <0.05 for all). In conclusion, according to the new Valve
      Academic Research Consortium-2 classification, 1 in every 6 patients in our
      cohort developed AKI after TAVI (most were stage 1 AKI). AKI was associated with
      increased mortality. No difference in AKI incidence was observed between
      different types and sizes of bioprostheses used. 

PMID- 24012025
TI  - Longitudinal follow-up of externalized Riata leads.
AB  - Riata family of implantable cardioverter defibrillator leads have demonstrated in
      situ conductor externalization, prompting a class I recall and the Food and Drug
      Administration recommendation for fluoroscopic screening. The natural history of
      externalized Riata leads, however, remains unclear. In this study, we examined
      the rate of electrical failure in Riata leads with externalized cables. We
      reviewed medical and implantable cardioverter defibrillator records of all 329
      patients with Riata leads who underwent fluoroscopic screening from December 2011
      to March 2012 at the University of Pittsburgh Medical Center hospitals.
      Externalization was present in 76 patients (23%); of whom, 24 (32%) had the Riata
      lead replaced shortly after screening. The remaining 52 patients were followed
      for 7.9 +/- 2.9 months, during which 5 patients were lost to follow-up and 2
      patients exhibited electrical lead failure resulting in lead replacement, an
      electrical failure rate of 6.4% per year in externalized leads. In conclusion,
      prospective follow-up data on externalized Riata leads suggest an electrical
      failure rate in excess of 6% per year. This high failure rate warrants
      consideration of prophylactic replacement of externalized Riata leads. Further
      studies examining the natural history of Riata leads are warranted.

PMID- 24012026
TI  - Cardiovascular complications of radiotherapy.
AB  - Chest radiotherapy is routinely used to treat malignancies such as Hodgkin
      disease and breast cancer but is commonly associated with a variety of
      cardiovascular complications involving the pericardium, myocardium, valves,
      coronary arteries, and conduction system. Cardiovascular complications are
      related to the total dose of radiation and the fractionation of the dose. They
      are usually progressive, portend poor prognosis, and are often refractory to
      treatment after significant radiation exposure. The mechanism of injury is
      multifactorial and likely involves endothelial damage of the microvasculature and
      coronary arteries and liberation of multiple inflammatory and profibrotic
      cytokines. In conclusion, routine follow-up with a cardiologist, which might
      include screening for valvular disease with echocardiography and coronary artery
      disease with computed tomography angiography or coronary artery calcium scoring,
      should be considered in patients with a history of chest radiotherapy. 

PMID- 24012027
TI  - Using simple imaging markers to predict prognosis in patients with aortic valve
      stenosis and unacceptable high risk for operation.
AB  - Aortic valve stenosis (AS) in patients >75 years of age is a challenge for
      diagnosis and management of every day clinical routine. Therefore, this clinical
      follow-up study aims to investigate predictors of death in patients with advanced
      stages of AS. In a single-center study, all patients (n = 157) with primary
      conservatively treated severe AS (mean age 78 +/- 6 years) were included. All
      patients had initially refused aortic valve replacement (AVR). During a median
      follow-up of 2.6 years (quartiles 1.7, 3.8), 62 patients with severe AS switched
      to AVR and 95 remained conservatively treated (no AVR). Routine clinical data
      were assessed together with conventional echocardiography including the
      measurement of longitudinal wall function and deformation (mitral ring
      displacement and longitudinal strain and strain rate imaging). The end points
      were all-cause and cardiac death. During follow-up, cardiac death occurred in 49%
      in no-AVR group. In a Cox regression analysis, New York Heart Association
      functional class, valvuloarterial impedance, stroke volume, longitudinal strain
      and strain rate, and mitral annular displacement identified an increased risk of
      all-cause death (hazard ratio [HR] for mitral annular displacement 15.9, 95%
      confidence interval [CI] 6.24 to 40.86, p <0.001, positive predictive value 91%).
      In contrast, ejection fraction or EuroSCORE was not predictive (ejection
      fraction: HR 1.3, 95% CI 0.82 to 2.33, p = 0.25; EuroSCORE: HR 1.1, 95% CI 0.64
      to 2.02, p = 0.64). Furthermore, in multivariate regression analysis, only
      longitudinal mitral annular displacement and longitudinal strain rate was a
      significant predictor of all-cause and cardiac death risk. These data show that
      prognosis in elderly patients with AS is determined by symptoms, hemodynamics,
      and particularly by cardiac long-axis function. Thus, for risk stratification, a
      comprehensive assessment of cardiac function including the measurement of
      longitudinal mitral annular displacement should be considered. 

PMID- 24012028
TI  - Effect of fragility on quality of life in patients with heart failure.
AB  - Heart failure (HF) is a chronic disease that frequently causes quality of life
      (QoL) impairment. We aimed to evaluate whether fragility affects QoL perception
      in outpatients with HF across age strata. The Minnesota Living with Heart Failure
      Questionnaire (MLWHFQ) was used to assess QoL, and fragility was defined
      according to basic standardized geriatric scales. Predefined criteria for such
      scales were scores of Barthel index <90, Older Americans' Resources and Services
      scale <10 in women and <6 in men, and Pfeiffer test >3 (+/-1 depending on
      educational grade) and >=1 positive depression response on the abbreviated
      Geriatric Depression Scale. We evaluated 1,405 consecutive outpatients with HF
      (27.8% women, median age 69 years [twenty-fifth to seventy-fifth percentiles: 59
      to 76 years]). Fragility, defined as at least 1 abnormal evaluation, was detected
      in 621 patients (44.2%). A positive depression response on the abbreviated
      Geriatric Depression Scale was the most prevalent (31.2%) component of fragility.
      We found a strong correlation between MLWHFQ score and the presence of fragility
      and all fragility components (all p <0.001). These associations prevailed in both
      younger (<75 years) and older patients (>=75 years; all p values <0.001 except
      for Pfeiffer test in younger patients [p = 0.007]). In multivariate regression
      analysis, QoL remained significantly associated with fragility after adjustment
      for age, gender, etiology of HF, left ventricular ejection fraction, New York
      Heart Association functional class, co-morbidities, and HF treatment, in both
      younger and older patients (p <0.001). In conclusion, MLWHFQ, a specific HF QoL
      questionnaire, is significantly influenced by fragility regardless of age. 

PMID- 24012029
TI  - Relation of hepatic steatosis to atherogenic dyslipidemia.
AB  - Hepatic steatosis is closely associated with the metabolic syndrome. We assessed
      for an independent association between hepatic steatosis and atherogenic
      dyslipidemia after adjustment for obesity, physical activity, hyperglycemia, and
      systemic inflammation. We studied 6,333 asymptomatic subjects without clinical
      cardiovascular disease undergoing a health screen in Brazil from November 2008 to
      July 2010. Hepatic steatosis was diagnosed by ultrasound. Atherogenic
      dyslipidemia was defined using 2 definitions: criteria for (1) metabolic syndrome
      or (2) insulin resistance (triglyceride/high-density-lipoprotein cholesterol
      ratio of >=2.5 in women and >=3.5 in men). In hierarchical multivariate
      regression models, we evaluated for an independent association of hepatic
      steatosis with atherogenic dyslipidemia. Hepatic steatosis was detected in 36% of
      participants (average age 43.5 years, 79% men, average body mass index 26.3
      kg/m(2)). Subjects with hepatic steatosis had similar levels of low-density
      lipoprotein cholesterol, with significantly lower level of high-density
      lipoprotein cholesterol and higher level of triglyceride compared with those
      without steatosis. Hepatic steatosis remained significantly independently
      associated with atherogenic dyslipidemia of both definitions (metabolic syndrome
      [odds ratio 2.47, 95% confidence interval 2.03 to 3.02] and insulin resistance
      [odds ratio 2.50, 95% confidence interval 2.13 to 2.91]) after multivariate
      adjustment. Stratified analyses showed a persistent independent association in
      nonobese subjects, those without metabolic syndrome, those with normal high
      sensitivity C-reactive protein, nonalcohol abusers, and those with normal liver
      enzymes. Hepatic steatosis was significantly associated with atherogenic
      dyslipidemia independent of obesity, physical activity, hyperglycemia, and
      systemic inflammation after multivariate adjustment. In conclusion, this adds to
      the growing body of evidence that hepatic steatosis may play a direct metabolic
      role in conferring increased cardiovascular risk. 

PMID- 24012030
TI  - Contemporary analysis of incidence and outcomes of stent thrombosis presenting as
      ST elevation myocardial infarction in a primary percutaneous coronary
      intervention cohort.
AB  - There are limited data about the effectiveness of primary percutaneous coronary
      intervention (PPCI) for stent thrombosis treatment. We aimed to evaluate the
      prevalence and outcomes of PPCI in patients with ST elevation acute myocardial
      infarction (STEMI) due to stent thrombosis, and comparing the outcomes with
      patients treated for de novo coronary thrombosis. This was an observational
      cohort study of 2,935 patients who underwent PPCI from 2003 to 2011 with follow
      up for a median of 3.0 years (interquartile range 1.2 to 4.6). The primary end
      point was the first major adverse cardiac event (MACE) defined as death, nonfatal
      myocardial infarction, stroke, or target vessel revascularization. Stent
      thrombosis overall accounted for 6.6% (194 of 2,935) of all STEMIs with a
      proportion that increased over time (3.3% in 2004 to 9.4% in 2011). A total of
      34.5% were early, 30.9% late stent thrombosis, and 34.5% were very late stent
      thrombosis. Indications for the original intervention were elective in 27.8%,
      after acute coronary syndrome (non-STEMI or unstable angina) in 21.1%, and after
      PPCI in 51.1%. Patients with stent thrombosis had higher rates of hypertension,
      hypercholesterolemia, diabetes, renal dysfunction, and previous myocardial
      infarction or coronary artery bypass surgery compared with patients with native
      artery occlusion. MACE rates were higher in patients with stent thrombosis
      compared with patients with native artery occlusions (40.9%, 95% confidence
      interval [CI] 31.1 to 50.6 vs 15.1%, 95% CI 12.5 to 18.3; p <0.0001). The poor
      outcome of stent thrombosis was particularly associated with early and late stent
      thromboses. Very late stent thrombosis appears to be a relatively less serious
      event, with similar outcomes to native vessel thromboses (MACE very late stent
      thrombosis 16.5%, 95% CI 8.2 to 28.6 vs native 15.1%, 95% CI 12.5 to 18.3, p =
      0.245). In conclusion, stent thrombosis accounts for an increasing proportion of
      STEMI and is associated with worse outcomes compared with native artery
      occlusion.

PMID- 24012031
TI  - Usefulness of tissue Doppler imaging for assessing left ventricular filling
      pressure in patients with stable severe systolic heart failure.
AB  - The ratio of early transmitral blood flow velocity over tissue Doppler early
      diastolic mitral annulus velocity (E/e') was found unreliable for estimating
      pulmonary capillary wedge pressure (PCWP) in patients with decompensated systolic
      heart failure (HF). The objective of this study was to test its reliability in
      stable HF. Therefore, 130 consecutive patients with a left ventricular (LV)
      ejection fraction of <35% and stable HF underwent right-sided cardiac
      catheterization and transthoracic echocardiography with measurement of
      transmitral flow velocities (E, A) and mitral annulus velocities during systole
      (s') and diastole (e'). Mean age was 56 +/- 11 years and mean LV ejection
      fraction was 28 +/- 8%; 48% had PCWP of >15 mm Hg. E/e'septal correlated more
      strongly with PCWP (r = 0.53) compared with E/e'lateral (r = 0.41) and E/e'mean
      (r = 0.50; all p values <0.001). The area under the receiver operating
      characteristic curve (AUC) of E/e' ratios for PCWP estimation was 0.79 (95%
      confidence interval [CI] 0.70 to 0.87) for E/e'septal, 0.72 (95% CI 0.63 to 0.82)
      for E/elateral, and 0.79 (95% CI 0.70 to 0.87) for E/emean (all p values
      <0.0001). AUCs of E/eseptal and E/emean did not vary with s'septal, QRS width, or
      resynchronization. Using a cutoff of 8, negative predictive value of E/e'septal
      was 89% and negative likelihood ratio of 0.15. E/e'lateral showed good diagnostic
      performance only in patients with s'lateral of >4.5 cm/s (n = 77, 59%; AUC =
      0.82; 95% CI 0.71 to 0.92; s'lateral of <=4.5 cm/s: AUC = 0.54; 95% CI 0.38 to
      0.70; p = 0.005). In conclusion, e' is useful for estimating LV filling pressure
      in stable severe systolic HF. E/e'septal showed good diagnostic performance for
      detecting normal filling pressures.

PMID- 24012032
TI  - Echocardiographic predictors of mitral regurgitation in high school and
      collegiate competitive athletes.
AB  - Previous studies have compared cardiac morphology between strength and endurance
      athletes, but few studies have examined predictors of valvular regurgitation in
      this population. This study evaluated predictors of mitral regurgitation (MR) in
      high school and collegiate athletes. Athletes in 9 different sports (n = 144)
      underwent transthoracic echocardiography. We used 97 sedentary patients as
      controls. Left ventricular (LV) end-diastolic diameter, septal wall thickness,
      posterior wall thickness, relative wall thickness (RWT), LV mass, LV volume, and
      mass/volume ratio were calculated and indexed for body surface area. Valvular
      regurgitation was graded from 0 to 4. Using logistic regression, RWT was
      associated with decreased odds of MR, with each 0.07 increase in RWT accounting
      for a 0.52 decrease in odds of MR (95% confidence interval 0.32 to 0.85, p =
      0.009). Differences were best exemplified by comparison of soccer and football
      players, who represent predominantly aerobic versus predominantly isometric
      exercise, respectively. Soccer players had a larger LV end-diastolic index (29.2
      +/- 3 vs 24.9 +/- 2.6, p <0.001), lesser RWT (0.33 +/- 0.06 vs 0.38 +/- 0.08, p =
      0.014), and lower mass/volume ratio (1.04 +/- 0.21 vs 1.29 +/- 0.3, p <0.001),
      with a greater prevalence of MR (45.8% vs 8.5%). Sedentary subjects were similar
      to football players in LV volume and soccer players in LV mass. In conclusion,
      RWT is a negative predictor of MR, with higher values reducing the odds of MR. MR
      appears to be related to the relation between wall thickness and chamber size
      rather than chamber size alone.

PMID- 24012033
TI  - A direct comparison of intravenous enoxaparin with unfractionated heparin in
      primary percutaneous coronary intervention (from the ATOLL trial).
AB  - Intravenous enoxaparin did not reduce significantly the primary end point (p =
      0.06) compared with unfractionated heparin (UFH) in the randomized Acute
      Myocardial Infarction Treated with primary angioplasty and intravenous enoxaparin
      Or unfractionated heparin to Lower ischemic and bleeding events at short- and
      Long-term follow-up (ATOLL) trial. We present the results of the prespecified per
      protocol analysis excluding patients who did not receive the treatment allocated
      by randomization or received both enoxaparin and UFH. We evaluated all-cause
      mortality, complication of myocardial infarction, procedural failure, or major
      bleeding (primary end point) and all-cause mortality, recurrent acute coronary
      syndrome, or urgent revascularization (main secondary end point). Baseline and
      procedural characteristics were well balanced between the 2 treatment groups. Of
      910 randomized patients, 795 patients (87.4%) were treated according to the
      protocol with consistent anticoagulation using intravenous enoxaparin (n = 400)
      or UFH (n = 395). Enoxaparin reduced significantly the rates of the primary end
      point (relative risk [RR] 0.76, 95% confidence interval [CI] 0.62 to 0.94, p =
      0.012) and the main secondary end point (RR 0.37, 95% CI 0.22 to 0.63, p
      <0.0001). There was less major bleeding with enoxaparin (RR 0.46, 95% CI 0.21 to
      1.01, p = 0.050) contributing to the significant improvement of the net clinical
      benefit (RR 0.46, 95% CI 0.3 to 0.74, p = 0.0002). All-cause mortality was also
      reduced with enoxaparin (RR 0.36, 95% CI 0.18 to 0.74, p = 0.003). In conclusion,
      in the per-protocol analysis of the ATOLL trial, pertinent to >87% of the study
      population, enoxaparin was superior to UFH in reducing ischemic end points and
      mortality.

PMID- 24012035
TI  - Impact of the severity of coronary artery calcification on clinical events in
      patients undergoing coronary artery bypass grafting (from the Acute
      Catheterization and Urgent Intervention Triage Strategy Trial).
AB  - The treatment of calcified coronary lesions by percutaneous coronary intervention
      has been shown to be associated with poor outcomes and an increased rate of
      complications. However, the impact of coronary calcification in patients
      undergoing coronary artery bypass grafting (CABG) is unknown. A total of 755
      patients presenting with acute coronary syndrome in the Acute Catheterization and
      Urgent Intervention Triage Strategy trial underwent CABG. Patients were divided
      into 3 groups according to the presence and extent of coronary calcifications
      (lesion level: severe, moderate, none to mild) as assessed by an independent
      angiographic core laboratory. Major ischemic and bleeding outcomes were assessed
      at 30 days and 1 year. Severe calcification was found in 103 patients (13.6%),
      moderate calcification in 249 patients (33.0%), and none-to-mild calcification in
      403 patients (53.4%). The presence of severe calcification compared with moderate
      or none to mild was associated with a significantly higher unadjusted rate of
      death (11.8% vs 3.7% vs 4.5%, p = 0.006), death or myocardial infarction (MI;
      31.1% vs 19.7% vs 16.4%, p = 0.006), and major adverse cardiac event (MACE; 32.0%
      vs 22.6% vs 20.8%, p = 0.059) at 1 year. By multivariate analysis, severe
      calcification (vs nonsevere calcification) was identified as an independent
      predictor of 1-year MACE (hazard ratio 1.49, 95% confidence interval 1.01 to
      2.21, p = 0.04) and death or MI (hazard ratio 1.77, 95% confidence interval 1.18
      to 2.66, p = 0.006). In conclusion, the presence of severe coronary calcification
      was associated with worse outcomes after CABG, including an increased risk of
      death. The presence of severe coronary calcification was identified as an
      independent predictor of MACE and death or MI 1 year after CABG. 

PMID- 24012034
TI  - Differences and similarities of repolarization patterns during hospitalization
      for Takotsubo cardiomyopathy and acute coronary syndrome.
AB  - Takotsubo cardiomyopathy (TC) is characterized by an acute transient left
      ventricular systolic dysfunction mimicking acute coronary syndrome (ACS) without
      significant coronary stenosis. The aim of this study was to examine the
      electrocardiographic repolarization patterns of TC and ACS and to compare them
      from hospital admission to hospital discharge. Forty-five patients with TC were
      matched with 45 patients with ACS according to age, gender, and presence or
      absence of ST elevation at hospital admission. A complete 12-lead
      electrocardiography was performed within 12 hours after symptoms onset and then
      repeated after 3, 5, and 7 days. All patients underwent coronary angiography, and
      patients with ACS also underwent percutaneous revascularization. Within 12 hours
      from the symptoms' onset, patients with TC had a significantly fewer number of
      leads with ST elevation and a significantly more number of leads with T-wave
      inversion. These differences, however, were not present after 72 hours and a
      similar trend was seen over time during the 7-day follow-up. Patients with TC had
      a significant longer corrected QT interval at admission and during the whole
      follow-up. In conclusion, in the electrocardiograms collected 12 hours within
      symptoms onset, patients with TC and those with ACS showed significant
      differences in cardiac repolarization. However, the number of leads with either
      ST-segment deviation or T-wave alterations in patients with TC soon matched the
      ACS group undergoing percutaneous revascularization. In contrast, corrected QT
      interval was persistently longer in patients with TC and, despite a similar
      reduction in length over time in both groups, it was still significantly longer
      after 7 days. 

PMID- 24012036
TI  - Effects of inhaled iloprost on exercise capacity, quality of life, and cardiac
      function in patients with pulmonary arterial hypertension secondary to congenital
      heart disease (the Eisenmenger syndrome) (from the EIGER Study).
AB  - There are limited data on the effect of iloprost therapy in patients with
      Eisenmenger syndrome (ES). The aim of our study was to evaluate the effect of
      inhaled iloprost therapy on exercise capacity, quality of life (QoL), cardiac
      function, and hemodynamics in patients with ES. Eighteen consecutive patients
      with ES and exertional dyspnea according to the World Health Organization
      functional class III or IV were prospectively recruited. Exercise capacity was
      assessed by a 6-minute walk test, and QoL was measured on a 12-Item Short-Form
      Health Survey. Echocardiographic measurements included peak systolic and mean
      pulmonary arterial pressures, pulmonary vascular resistance, and myocardial
      performance index of the right ventricle (RV). All patients underwent
      comprehensive evaluation at baseline and after 24 weeks of treatment. Of the 18
      patients with ES, 13 were included for analysis. After 24 weeks of iloprost
      therapy, 6-minute walk test distance significantly increased (289.1 +/- 76.9 to
      369.5 +/- 93.4 m, p = 0.032) in addition to concomitant improvements in the 12
      Item Short-Form Health Survey physical and mental component summaries (20.6 +/-
      19.3 to 52.6 +/- 28.0, p <0.05; 33.9 +/- 19.7 to 54.9 +/- 21.3, p <0.05,
      respectively). RV myocardial performance index improved significantly after
      treatment (0.80 +/- 0.31 to 0.59 +/- 0.12, p = 0.042). Pulmonary arterial
      pressure and pulmonary vascular resistance did not improve with iloprost therapy.
      This study showed that 24 weeks of inhaled iloprost therapy in patients with ES
      led to significant improvements in exercise capacity, QoL, and RV function. These
      results likely explain the symptomatic relief reported by patients with ES
      receiving iloprost therapy. 

PMID- 24012037
TI  - Contemporary surgical management of hypertrophic cardiomyopathy, the need for
      more myectomy surgeons and disease-specific centers, and the Tufts initiative.

PMID- 24012038
TI  - Enhanced recovery in obstetrics.

PMID- 24012039
TI  - Placenta accreta: successful outcome is all in the planning.

PMID- 24012040
TI  - Comparative effectiveness and survival of infliximab, adalimumab, and etanercept
      for rheumatoid arthritis patients in the Hellenic Registry of Biologics: Low
      rates of remission and 5-year drug survival.
AB  - OBJECTIVE: To compare effectiveness, drug survival, and safety between
      infliximab, adalimumab, and etanercept, in a nationwide cohort of rheumatoid
      arthritis (RA) patients. METHODS: This study is a prospective cohort study of
      1208 active RA patients. Effectiveness, drug survival, and serious adverse events
      during entire follow-up (median 2.9 years) were monitored. RESULTS: EULAR and
      CDAI responses were comparable between the three agents (EULAR good/moderate
      responses at 12 months ranged 76-79%). At 12 months, 15-23% achieved remission.
      For adalimumab and etanercept, adjusted hazard rate (HR) for EULAR/ACR remission
      (reference: infliximab) was 2.7 and 2.1 (95% confidence interval was 1.7-4.1 and
      1.3-3.4, respectively); males (HR 1.6; 1.1-2.4), use of glucocorticoids (HR 2.0;
      1.3-3.0), and swollen joint count >7 (HR 0.36; 0.24-0.55) were independent
      predictors. Five-year drug survival was 31%, 43%, and 49% for infliximab,
      adalimumab, and etanercept, respectively (p = 0.010). Infliximab was associated
      with significantly more withdrawals due to adverse events. Disease activity, CRP,
      and use of glucocorticoids predicted efficacy-related drug survival; age, use of
      methotrexate, and prior DMARDs failures predicted safety-related survival. Risk
      for serious infections was lower with adalimumab (odds ratio [OR] 0.62; 0.38
      1.00) or etanercept (OR 0.39; 0.21-0.72) than infliximab, independent of the
      effects of age (OR 1.65; 1.37-2.00 per 10 years), tender joint count >10 (OR
      1.86; 1.21-2.86), and glucocorticoids >35mg/week (OR 1.83; 1.12-2.99).
      CONCLUSIONS: Response rates were comparable among anti-TNF agents. Overall, 5
      year drug survival was below 50%, with infliximab demonstrating increased safety
      related discontinuations. Remission rates are low in clinical practice.
      Strategies to increase effectiveness and long-term survival of anti-TNF agents in
      RA are needed.

PMID- 24012041
TI  - Pachydermoperiostosis in an African patient caused by a Chinese/Japanese SLCO2A1
      mutation-case report and review of literature.
AB  - OBJECTIVES: Pachydermoperiostosis is a rare clinical entity characterized by skin
      thickening of the forehead, eyelids, and hands, digital clubbing, and
      periostosis. Two genes have been associated, HPGD and recently SLCO2A1. We
      present a detailed clinical and genetic description of an African
      pachydermoperiostosis patient with a SLCO2A1 mutation. METHODS: Standard clinical
      and laboratory evaluation was carried out. Genetic screening was done with PCR
      followed by direct sequencing. We discuss the clinical features and known
      mutations of previously reported cases identified through a PubMed literature
      review. RESULTS: The clinical findings showed special features, including
      exuberant knee effusions and an extraordinary good response on surgery of the
      blepharoptosis. We found a splice site mutation in the SLCO2A1 gene in homozygous
      form: c.940+1G>A. This mutation was previously reported only in 1 Chinese and 3
      Japanese cases and was considered as a founder mutation in Japan. Beside our
      case, only one other patient in the literature carried this mutation in
      homozygous condition, but with different main clinical symptoms. CONCLUSIONS: Our
      case demonstrates phenotypic heterogeneity of PDP even between homozygous
      carriers of the same mutation, suggesting further modifiers. Besides, it shows
      that this rare SLCO2A1 mutation is not exclusively present in East-Asia, but can
      occur in various ethnicities, with different origin, thus the incidence is
      probably underestimated.

PMID- 24012042
TI  - Evolution of cardiac dysfunction in patients with antiphospholipid antibodies
      and/or antiphospholipid syndrome: a 10-year follow-up study.
AB  - OBJECTIVES: To describe the evolution of valve involvement and myocardial
      dysfunction over time in patients with systemic lupus erythematosus (SLE) with or
      without antiphospholipid antibodies (aPL) and/or antiphospholipid syndrome (APS).
      METHODS: From an initial cohort of 150 patients assessed by transthoracic
      echocardiography 10 years ago, 17 patients with primary APS (PAPS), 23 with SLE
      associated APS (SLE/APS), 19 with SLE positive for aPL without APS, and 23 with
      SLE negative for aPL were re-evaluated in the present echocardiography study.
      RESULTS: Valvulopathy was detected in 65% of PAPS and 62% of SLE patients with or
      without aPL. Disease duration [odds ratio (OR), 1.63; 95% confidence interval
      (CI), 1.13-2.36; p = 0.009 for every 5 years of increase] and presence of SLE/APS
      (OR, 3.51; 95% CI, 1.27-9.67; p = 0.015) were the only factors associated with
      the progression of valvular disease in univariate and multivariate analyses. Left
      ventricular diastolic dysfunction similarly progressed over time, with
      deceleration time (DT) and isovolumic relaxation time (IVRT) being equally
      prolonged in each of the four groups (p < 0.05). Right ventricular DT was
      significantly prolonged in each of the three SLE patient groups (p < 0.001),
      whereas IVRT increased only in SLE/APS patients (p = 0.040). CONCLUSIONS: Among
      patients with APS and SLE (with or without aPL), SLE/APS and disease duration
      were independent factors for valvular disease progression in the present 10-year
      follow-up echocardiography study. Anticoagulation did not arrest valvular disease
      progression. Ventricular diastolic dysfunction, primarily of the left ventricle,
      also progressed over the 10-year period.

PMID- 24012043
TI  - Comparative cancer risk associated with methotrexate, other non-biologic and
      biologic disease-modifying anti-rheumatic drugs.
AB  - OBJECTIVE: There is little information comparing the potential risk of cancer
      across conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs)
      in patients with rheumatoid arthritis (RA). Methotrexate has not been the focus
      of most contemporary pharmacoepidemiologic studies of cancer. METHODS: We
      conducted a comparative effectiveness study with cancer as the outcome. A large
      observational cohort of RA was followed up from 2001 to 2010. Reports of any
      cancer prompted a confirmation process that included adjudication of the primary
      cancer records. We used a propensity score (PS) with relevant covariates and
      cohort trimming to improve the balance between DMARD cohorts. Cox proportional
      hazard regression models were constructed to estimate the risk of cancer with
      various DMARDs, all compared with methotrexate. RESULTS: We identified 6806 DMARD
      courses for analysis (1566 methotrexate; 904 nbDMARDs; 3761 TNF antagonists; 408
      abatacept; and 167 rituximab). Non-biologic DMARDs (HR 0.17, 95% CI 0.05-0.65)
      and TNF antagonists (HR 0.29, 95% CI 0.05-0.65) were associated with a reduced
      adjusted risk of cancer compared with methotrexate. Abatacept (HR 1.55, 95% CI
      0.40-5.97) and rituximab (HR 0.42, 95% CI 0.07-2.60) were similar in risk of
      cancer with methotrexate. These results were robust to sensitivity analyses.
      After controlling for DMARD exposures, risk factors for cancer included male
      gender, age, and alcohol consumption. CONCLUSIONS: Cancer risk was elevated for
      methotrexate users compared with nbDMARDs and TNF antagonists.

PMID- 24012044
TI  - Screening and diagnostic modalities for connective tissue disease-associated
      pulmonary arterial hypertension: a systematic review.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) is a frequent complication in
      connective tissue diseases (CTD), especially in systemic sclerosis (SSc), and is
      associated with a high degree of morbidity and mortality. We undertook a
      systematic review for the screening tests for CTD-PAH. METHODS: A systematic
      literature search of PAH in CTD was performed in available databases through June
      2012. Our evaluation of diagnostic tests was focused on patients with PAH
      confirmed by right heart catheterization (RHC). RESULTS: The search resulted in
      2805 titles and 838 abstracts. Our final inclusion encompassed 22 articles-six of
      which were case-control studies and 16 were cohort studies. Twelve studies
      assessed the tricuspid regurgitation velocity (VTR) or equivalent right
      ventricular systolic pressure (RVSP) using transthoracic echocardiogram (TTE) as
      a threshold for RHC in patients suspected as having PAH. The screening threshold
      for RHC was VTR from >2.73 to >3.16 m/s without symptoms or 2.5-3.0m/s with
      symptoms and resulted in 20-67% of patients having RHC-proven PAH. Three studies
      looked at pulmonary function tests and found that a low lung diffusing capacity
      for carbon monoxide (DLCO) (45-70% of predicted) is associated with a 5.6-7.4%
      development of PAH, and a decline in DLCO% is associated with an increase in the
      specificity (for DLCO <= 60%, spec = 45%; and for DLCO <= 50%, spec = 90%) for
      PAH. Five studies assessed N-terminal prohormone of brain natriuretic peptide (NT
      ProBNP), where a cutoff >239 pg/ml had a sensitivity of 90-100%. CONCLUSIONS: Our
      systematic review revealed that most evidence exists for TTE, pulmonary function
      tests, and NT-ProBNP for screening and diagnosis of SSc-PAH; however, more robust
      studies are needed.

PMID- 24012045
TI  - Incidence of total knee and hip replacement for osteoarthritis in relation to the
      metabolic syndrome and its components: a prospective cohort study.
AB  - OBJECTIVE: To examine whether components of metabolic syndrome (MetS), either
      singly or additively, were associated with the incidence of severe knee and hip
      OA, and whether these associations were independent of obesity assessed by body
      mass index (BMI). METHODS: Twenty thousand, four hundred and thirty participants
      who had blood lipids, anthropometric and blood pressure measurements during 2003
      2007 were selected from the Melbourne Collaborative Cohort Study. MetS was
      defined as central obesity assessed by waist circumference and any two of raised
      triglyceride level, reduced HDL cholesterol level, hypertension or impaired
      fasting glycaemia. The incidence of total knee and hip replacement was determined
      by linking cohort records to the Australian Orthopaedic Association National
      Joint Replacement Registry. RESULTS: Six hundred and sixty participants had knee
      OA and 562 had hip OA. After adjustment for age, gender, country of birth,
      education, physical activity and BMI, central obesity [hazard ratio (HR) 1.59,
      95% confidence interval (CI) 1.25-2.01] and hypertension (1.24, 1.05-1.48) were
      associated with increased risk of knee OA. The accumulation of MetS components
      was associated with knee OA risk, independent of BMI: one component, 2.12 (1.15
      3.91); two components, 2.92 (1.60-5.33) and three or more components, 3.09 (1.68
      5.69). No statistically significant associations were observed for hip OA.
      CONCLUSION: Cumulative number of MetS components and central obesity and
      hypertension were associated with increased risk of severe knee OA, independent
      of BMI. No associations were observed with severe hip OA. These findings suggest
      that the pathogenesis of knee and hip OA differ and that targeting the management
      of MetS may reduce the risk of knee OA.

PMID- 24012046
TI  - Female polysomy-X and systemic lupus erythematosus.
AB  - OBJECTIVES: Systemic lupus erythematosus (SLE) occurs more commonly in females
      than in males. Recent evidence suggests that genetic factors transmitted by the X
      chromosome may confer increased risk for autoimmune disease in general, and for
      SLE in particular. It is therefore possible that X-chromosome polysomy might
      confer further increased risk for lupus. In addition to describing the clinical
      and immunologic features of a young woman with polysomy-X and SLE, we sought to
      review all other published cases associating female or male polysomy-X with SLE
      or other forms of autoimmunity. METHODS: We report a case of a prepubertal girl
      with polysomy-X and SLE. We performed a systemic literature review for cases of
      polysomy-X and SLE and summarize previously published cases. In addition, we
      reviewed reports concerning the possible association between SLE and other
      connective tissue diseases and male polysomy-X. RESULTS: An 11-year-old girl with
      tetrasomy-X (48 XXXX karyotype) presented with prolonged fever. Workup led to the
      diagnosis of SLE, and subsequent renal biopsy revealed mild diffuse mesangial
      proliferative glomerulonephritis. Two additional cases of SLE in women with 47
      XXX and one of 48 XXXX karyotype were found in a literature review and compared
      to the present case. We identified studies that found X-chromosome polysomy to be
      over-represented in male patients with SLE and case descriptions of connective
      tissue diseases occurring in patients with polysomy-X. CONCLUSION: No consistent
      pattern of disease was observed in female polysomy patients with SLE. Taken
      together with the data concerning the frequency of polysomy-X among males with
      SLE, our findings provide additional support for the hypothesis that X-chromosome
      polysomy may confer increased susceptibility to SLE. Molecular mechanisms that
      might account for this phenomenon are discussed.

PMID- 24012047
TI  - Assessment of relationship on excess fluoride intake from drinking water and
      carotid atherosclerosis development in adults in fluoride endemic areas, China.
AB  - Cross-sectional analysis was conducted to access the relationships between
      developing carotid artery atherosclerosis through consuming high fluoride in
      drinking water and its possible mechanism, using the baseline data collected from
      585 study subjects. In the cross sectional analysis, subjects were divided into
      four groups based on the concentrations of fluoride in their drinking water. The
      range of fluoride concentrations was: normal group (less than 1.20 mg/L), mild
      group (1.21-2.00 mg/L), moderate group (2.01-3.00 mg/L), and high concentration
      group (more than 3.01 mg/L). The prevalence rate of carotid artery
      atherosclerosis in the subjects in each group was found to be 16.13%, 27.22%,
      27.10%, and 29.69%, respectively. Significant difference between the prevalence
      of carotid artery atherosclerosis in the mild, moderate and high fluoride
      exposure group and in the normal group was observed (P<0.05). In addition, it was
      found that elevated intercellular cell adhesion molecule-1 (ICAM-1) and reduced
      glutathione peroxidases (GPx) was associated with carotid artery atherosclerosis
      in fluoride endemic areas. The findings of the research study revealed a
      significant positive relationship between excess fluoride exposure from drinking
      water and prevalence of carotid artery atherosclerosis in adults living in
      fluoride endemic areas. The possible mechanism was the excess fluoride induced
      the decreasing level of GPx causing the systemic inflammation and endothelial
      activation by oxidative stress.

PMID- 24012048
TI  - Dysregulation of cytokines expression in complicated falciparum malaria with
      increased TGF-beta and IFN-gamma and decreased IL-2 and IL-12.
AB  - BACKGROUND: In Plasmodium falciparum infections, proinflammatory cytokine
      response is implicated in control of parasite multiplication as well as in
      disease pathogenesis. However, the regulation of proinflammatory and anti
      inflammatory cytokine balance and its relation to disease severity remains poorly
      understood. METHODS: We examined cytokines gene expression by quantitative real
      time-PCR technique in a case control study comprising of P. falciparum infected
      (n=58) and non infected (n=30) groups. P. falciparum infected were further
      stratified as complicated and uncomplicated as per WHO criterion and parasitaemia
      levels. RESULTS: Higher expression of IL-2, IL-12alpha and TGF-beta with
      decreased levels of IL-10 was seen in P. falciparum positivity. Complicated
      malaria was associated with enhanced expression of IFN-gamma and TGF-beta but
      lower IL-2 and IL-12alpha in comparison to uncomplicated malaria. Modeling of
      data suggested higher expression of IL-12alpha to be predictive of uncomplicated
      malaria [Odds ratio=3.074, 95% CI (1.254-7.536)] and was negatively associated
      with complicated malaria outcome (p=0.014). Interestingly, the probability of
      complicated malaria in males with elevated TNF-alpha expression was three times
      higher [p=0.05; Odds ratio=3.412, 95% CI (0.98-11.848)]. Age was also seen to be
      a factor with higher IL-8 in diseased young (p=0.012). CONCLUSION: Our data
      suggested induction of balanced cytokine response in uncomplicated malaria while
      cytokine dysregulation with a role for TGF-beta was indicated in complicated
      malaria. TH cells did not appear to be the source of increased IFN-gamma
      expression associated with malaria severity.

PMID- 24012049
TI  - Generalized periodic discharges after acute cerebral ischemia: reflection of
      selective synaptic failure?
AB  - OBJECTIVES: Generalized periodic discharges (GPDs) can be observed in the
      electroencephalogram (EEG) of patients after acute cerebral ischemia and reflect
      pathological neuronal synchronization. Whether GPDs represent ictal activity,
      which can be treated with anti-epileptic drugs, or severe ischemic damage, in
      which treatment is futile, is unknown. We hypothesize that GPDs result from
      selective ischemic damage of glutamatergic synapses, which are known to be
      relatively vulnerable to effects of ischemia. METHODS: We employed a macroscopic
      model of cortical dynamics in which we increasingly eliminated glutamatergic
      synapses. We compared the output of the model with clinical EEG recordings in
      patients showing GPDs after cardiac arrest. RESULTS: Selective elimination of
      glutamatergic synapses from pyramidal cells to inhibitory interneurons led to
      simulated GPDs whose waveshape and frequency matched those of patients showing
      GPDs after cardiac arrest. Mere reduction of glutamatergic synapses between
      pyramidal cells themselves did not result in GPDs. CONCLUSIONS: Selective
      ischemic damage of glutamatergic synapses on inhibitory cortical interneurons
      leads to the generation of ischemia induced GPDs. Disinhibition of cortical
      pyramidal neurons is a candidate mechanism. SIGNIFICANCE: This study increases
      the insight in the pathophysiological mechanisms underlying the generation GPDS
      after acute cerebral ischemia.

PMID- 24012050
TI  - Primary somatosensory cortical plasticity and tactile temporal discrimination in
      focal hand dystonia.
AB  - OBJECTIVE: To investigate whether theta burst stimulation (TBS) applied over
      primary somatosensory cortex (S1) modulates somatosensory temporal discrimination
      threshold (STDT) and writing performances in patients with focal hand dystonia
      (FHD). METHODS: Twelve patients with FHD underwent STDT testing and writing tasks
      before and after intermittent, continuous, or sham TBS (iTBS, cTBS, sham TBS)
      over S1 contralateral to the affected hand. Twelve healthy subjects underwent
      iTBS and cTBS over S1 and STDT values were tested on the right hand before and
      after TBS. RESULTS: Baseline STDT values were higher in patients than in healthy
      subjects on both the affected and unaffected hand. In patients and healthy
      subjects iTBS decreased, whereas cTBS increased STDT values and did so to a
      similar extent in both groups. In patients, although STDT values decreased after
      iTBS, they did not normalize. S1 modulation did not improve the writing
      performance. CONCLUSIONS: In patients, S1 responds normally to protocols inducing
      homotopic synaptic plasticity. The inhibitory interneuron activity responsible
      for STDT is altered. SIGNIFICANCE: The pathophysiological mechanisms underlying
      abnormal temporal discrimination differ from those responsible for motor symptoms
      in FHD.

PMID- 24012051
TI  - Characterisation of explosive fragments injuring the neck.
AB  - Penetrating explosive fragments are the most common cause of neck injuries
      sustained by UK service personnel deployed to Afghanistan. Analysis of these
      fragments will enable future ballistic protective materials to be tested with
      appropriate projectiles. However, only a small number of fragments excised from
      the neck have been available for analysis and they are potentially
      unrepresentative. We analysed computed tomograms (CTs) of 110 consecutive UK
      soldiers whose necks were wounded by explosive fragments. Fragments were
      classified according to shape, and their dimensions used to estimate volume and
      mass. These calculations were then compared with the actual measurements of the
      excised fragments using a general linear model. The 2 most common shapes were
      cylinders (52%) and spheres (21%). Known and estimated masses were not
      significantly different (p=0.64). A fragment-simulating projectile of 0.49 g
      represented 85% of fragments retained in the neck. CT can accurately delineate
      the shape and mass of fragments, which increases the number from which the most
      appropriate simulated projectile can be designed. We think that this methodology
      should be applied to fragments retained in other parts of the body to enable
      broader recommendations to be made regarding the testing of ballistic materials
      used to protect service personnel.

PMID- 24012052
TI  - Upper eyelid incision and use of a 90 degrees  screwdriver for osteosynthesis of
      fractures of the anterior table of the frontal sinus.

PMID- 24012053
TI  - The role of postoperative prophylactic antibiotics in the treatment of facial
      fractures: a randomized, double-blind, placebo-controlled pilot clinical study.
      Part 2: Mandibular fractures in 59 patients.
AB  - The aim of this study was to evaluate the difference between a 5-day and a 1-day
      postoperative course of antibiotic on the incidence of infection after mandibular
      fractures involving the alveolus. Sixty-two patients with fractures of the
      mandible involving the dentoalveolar region were randomly assigned to 2 groups,
      both of which were given amoxicillin/clavulanic acid 1.2 g intravenously every 8
      h from admission until 24 h postoperatively. The 5-day group were then given
      amoxicillin/clavulanic acid 625 mg orally every 8 h for another 4 days. The 1-day
      group was given an oral placebo at the same intervals. Follow-up appointments
      were 1, 2, 4, 6, 12 weeks and 6 months postoperatively. Development of an
      infection was the primary end point. Fifty-nine of the 62 patients completed this
      study. Six of the 30 patients in the 5-day group (20%) and 6 out of the 29 in the
      1-day group (21%) developed local wound infections. Three of the 6 in the 1-day
      group developed purulent discharge and swelling. One patient in the 5-day group
      developed a rash on the trunk. There were no significant differences in the
      incidence of infection or side effects between the groups. In fractures of the
      mandible involving the alveolus, a 1-day postoperative course of antibiotic is as
      effective in preventing infective complications as a 5-day regimen.

PMID- 24012055
TI  - Facial calcinosis: case report.
AB  - Antisynthetase syndrome is a subgroup of the idiopathic inflammatory muscle
      diseases and is characterised by myositis, interstitial pulmonary disease,
      arthritis, and Raynaud phenomenon. We report the case of a 34-year-old woman with
      known antisynthetase syndrome who presented with subcutaneous calcinosis
      bilaterally in the submandibular region. 

PMID- 24012054
TI  - Factors that are associated with injury to the inferior alveolar nerve in high
      risk patients after removal of third molars.
AB  - Our aim was to answer the question: "Among patients at high risk of injury to the
      inferior alveolar nerve (IAN) after removal of 3rd molars, what factors are
      associated with postoperative neurosensory deficits?" We organized a
      retrospective, two-center study and enrolled a group of subjects who were at
      increased risk of injury to the IAN after removal of 3rd molars because
      radiographic findings indicated a risk on panoramic radiography that was high
      enough to warrant preoperative computed tomography (CT). The primary outcome
      variable was postoperative injury to the IAN. We used descriptive, bivariate, and
      multivariate analyses to assess the significance of differences, and
      probabilities of less than 0.05 were accepted as significant. We studied 149
      subjects who had 235 3rd molars removed. Their mean (SD) age was 31 (11) years
      and 25/235 (11%) of 3rd molars were associated with injury to the IAN. In the
      multiple logistic regression model, increasing age (odds ratio (OR) 1.05, 95% CI
      1.01-1.1, p=0.04), female sex (OR 5.3, 95% CI 1.6-16.9, p=0.005), and the size
      (mm) of the cortical perforation in the inferior alveolar canal (IAC) viewed on
      the coronal CT cut (OR 1.3; 95% CI 1.0-1.6, p=0.03) were associated with an
      increased risk of postoperative injury to the IAN. Age, sex, and the size of the
      perforation in the IAC on the coronal CT were associated with an increased risk
      of injury to the IAN. These findings may help to guide recommendations for
      treatment of patients at high risk of injury to the IAN during removal of 3rd
      molars. 

PMID- 24012056
TI  - Association of Egr-1 and autophagy-related gene polymorphism in men with chronic
      obstructive pulmonary disease.
AB  - BACKGROUND/PURPOSE: Autophagy is important in cellular homeostasis and control of
      inflammatory immune response. Increased autophagy has recently been associated
      with increased cell death and chronic obstructive pulmonary disease (COPD)
      pathogenesis. Two autophagy regulator genes have been identified: Egr-1 (early
      growth response), associated with different phenotype expressions in asthma; and,
      Atg16L1 (autophagy related 16-like 1), a candidate gene responsible for
      susceptibility to chronic inflammatory diseases. We will explore the role of the
      Egr-1 and Atg16L1 gene polymorphisms in COPD. METHODS: The genotypes of 151 male
      smoking patients with COPD and 100 male smoking controls were evaluated by
      polymerase chain reaction followed by restriction fragment length polymorphism
      analysis of the Egr-1 (-4071 A -> G) rs7729723 and Atg16L-1 (T300A) rs2241880
      variants. RESULTS: The G allele of the Egr-1 gene polymorphism was associated
      with an increased risk of developing COPD [odds ratio (OR), 2.05; 95% confidence
      interval (CI), 1.15-3.72], and participants with the G allele polymorphism (GG
      and GA genotypes) had a 2.56-fold higher risk (OR, 2.56; 95% CI, 1.31-5.16) of
      having COPD than those homozygous for the A allele [35.8% (54/151) vs. 24.0%
      (24/100); p = 0.007]. Participants with the A allele of the Atg16L1 gene
      polymorphism (AA and AG genotypes) had a 3.34-fold higher risk (OR, 3.34; 95% CI,
      1.32-8.97) of having COPD than those homozygous for the G allele [93.4% (141/151)
      vs. 81.0% (81/100); p = 0.013]. CONCLUSION: The Egr-1 and Atg16L1 genes'
      polymorphisms were significant risk factors for susceptibility to COPD. These
      results demonstrate that autophagy regulator genetic mutations are associated
      with COPD in male smokers.

PMID- 24012057
TI  - Planning and evaluation in health workforce development: projection for the
      pharmacy workforce in Taiwan.

PMID- 24012058
TI  - The excision of 3' penultimate errors by DNA polymerase I and its role in
      endonuclease V-mediated DNA repair.
AB  - Deamination of adenine can occur spontaneously under physiological conditions,
      and is enhanced by exposure of DNA to ionizing radiation, UV light, nitrous acid,
      or heat, generating the highly mutagenic lesion of deoxyinosine in DNA. Such DNA
      lesions tends to generate A:T to G:C transition mutations if unrepaired. In
      Escherichia coli, deoxyinosine is primarily removed through a repair pathway
      initiated by endonuclease V (endo V). In this study, we compared the repair of
      three mutagenic deoxyinosine lesions of A-I, G-I, and T-I using E. coli cell-free
      extracts as well as reconstituted protein system. We found that 3'-5' exonuclease
      activity of DNA polymerase I (pol I) was very important for processing all
      deoxyinosine lesions. To understand the nature of pol I in removing damaged
      nucleotides, we systemically analyzed its proofreading to 12 possible mismatches
      3'-penultimate of a nick, a configuration that represents a repair intermediate
      generated by endo V. The results showed all mismatches as well as deoxyinosine at
      the 3' penultimate site were corrected with similar efficiency. This study
      strongly supports for the idea that the 3'-5' exonuclease activity of E. coli pol
      I is the primary exonuclease activity for removing 3'-penultimate deoxyinosines
      derived from endo V nicking reaction. 

PMID- 24012061
TI  - Assessment of coronary artery disease risk in 5463 patients undergoing cardiac
      surgery: when is preoperative coronary angiography necessary?
AB  - OBJECTIVES: We sought to critically analyze the routine use of conventional
      coronary angiography (CCA) before noncoronary cardiac surgery and to assess
      clinical prediction models that might allow more selective use of CCA in this
      setting. METHODS: We studied 5463 patients undergoing aortic valve surgery,
      mitral valve surgery, or septal myectomy with or without coronary artery bypass
      grafting from 2001 to 2010. Preoperative CCAs were evaluated for the presence of
      significant coronary artery disease (CAD). Random forests and logistic regression
      methods were used to determine the predictors of significant (>=50%) coronary
      stenosis. RESULTS: Preoperative CCA was performed in 4711 patients (86%). Two
      thirds of those with angina, previous myocardial infarction, or percutaneous
      coronary intervention had significant CAD found on CCA, versus one third of
      patients free of these risk factors (P < .001). Among 3019 patients without
      angina, previous myocardial infarction or percutaneous coronary intervention,
      older age, male gender, diabetes, and peripheral vascular disease independently
      predicted significant CAD (P < .001 for all; C-index = 0.74). Specifically, a
      multivariate model with these variables identified 10% (301 of 3019) of patients
      as having a low (<=10%) probability of coronary stenosis, of whom fewer than 5%
      had significant CAD and fewer than 1% had left main or triple-vessel coronary
      disease. CONCLUSIONS: In the absence of angina, previous myocardial infarction,
      or percutaneous coronary intervention, preoperative CCA identified significant
      CAD in only one third of patients. Our clinical prediction models could enhance
      the identification of patients at low risk of significant CAD for whom CCA might
      potentially be avoided before cardiac surgery. This strategy may improve the
      efficiency of cardiac surgical care delivery by diminishing procedure-related
      morbidity and offering significant cost savings.

PMID- 24012062
TI  - Giant lateral spreading tumor in ulcerative colitis.

PMID- 24012059
TI  - Rhodopsin homeostasis and retinal degeneration: lessons from the fly.
AB  - Rhodopsins (Rh) are G protein-coupled receptors that function as light-sensors in
      photoreceptors. In humans, Rh mutations cause retinitis pigmentosa (RP), a
      degenerative disease that ultimately results in blindness. Studies in Drosophila
      have provided many insights into basic Rh biology and have identified pathways
      that lead to retinal degeneration. It has been shown that, because Rh is very
      abundant in photoreceptors, its accumulation in numerous organelles induces
      severe stress and results in degeneration of these cells. Moreover, genetic
      lesions that affect proper activation of membrane-bound Rh lead to disruption in
      Ca(2+) homeostasis which also causes photoreceptor degeneration. We review here
      the molecular signals involved in Rh homeostasis and the mechanisms underlying
      retinal degeneration in flies, and discuss possible links to human diseases. 

PMID- 24012063
TI  - Combined oral and rectal mesalazine for the treatment of mild-to-moderately
      active ulcerative colitis: rapid symptom resolution and improvements in quality
      of life.
AB  - BACKGROUND AND AIMS: Mesalazine (5-aminosalicylic acid) is the standard first
      line therapy for mild-to-moderate ulcerative colitis. In the PINCE study,
      remission rates were significantly greater with combined oral/enema vs.
      oral/placebo treatment at 8 weeks (64% vs. 43%, respectively; p=0.030). In this
      analysis, we explored early response, mucosal healing rates, cessation of rectal
      bleeding, and quality of life in PINCE. METHODS: Patients with extensive mild-to
      moderately active ulcerative colitis received 8weeks of oral mesalazine 4 g/day,
      plus 4 weeks of daily active (1g mesalazine) or placebo enema. Early response was
      assessed using the abbreviated ulcerative colitis disease activity index. Mucosal
      healing was assessed by disease activity index endoscopic mucosal appearance
      score. Cessation of bleeding (patient diaries), quality of life (EQ-5D), and
      patient acceptability (questionnaire) were also assessed. RESULTS: Combined
      mesalazine oral/enema treatment achieved a significantly higher rate of
      improvement in abbreviated ulcerative colitis disease activity index (score
      decrease >= 2) within 2 weeks, compared with oral-only treatment (p = 0.032).
      Bleeding ceased significantly more quickly with combination vs. oral therapy (p =
      0.003). More patients showed mucosal healing (disease activity index endoscopic
      mucosal appearance score 0/1) with combination vs. oral therapy, which was
      significantly different between groups at week 4 (p = 0.052). Both groups showed
      quality of life improvements, with a significant benefit for combination vs. oral
      therapy at week 4 in multiple domains. Most patients reported finding the
      treatment acceptable. CONCLUSIONS: Rapid cessation of symptoms was seen with
      combination therapy, which is particularly important to patients and may improve
      quality of life.

PMID- 24012064
TI  - Cigarette packaging: Youth perceptions of "natural" cigarettes, filter
      references, and contraband tobacco.
AB  - PURPOSE: The current study examined youth perceptions of appeal and harm of
      cigarette packaging with "natural" tobacco descriptors and references to
      filtration, as well as contraband tobacco in generic packaging. METHODS: In a
      between-group experiment, 7,647 youth were randomized to view a pair of cigarette
      packages and rate perceptions of appeal and relative risk. RESULTS: The findings
      indicate that packages with "natural" descriptors were rated as significantly
      more appealing and less harmful. Packages with filter references were rated as
      significantly less harmful, whereas contraband cigarettes were rated as
      significantly less appealing than leading brands. CONCLUSIONS: The findings
      suggest that cigarette packaging can enhance the appeal of cigarettes and may
      promote false beliefs about the reduced harm of brands. The lower appeal of
      contraband cigarettes suggests that other factors, such as reduced price and ease
      of access, likely account for contraband use among youth.

PMID- 24012065
TI  - Peer influences: the impact of online and offline friendship networks on
      adolescent smoking and alcohol use.
AB  - PURPOSE: Online social networking sites (SNSs) have become a popular mode of
      communication among adolescents. However, little is known about the effects of
      social online activity on health behaviors. The authors examined the use of SNSs
      among friends and the degree to which SNS activities relate to face-to-face peer
      influences and adolescent risk behaviors. METHODS: Longitudinal egocentric
      friendship network data along with adolescent social media use and risk behaviors
      were collected from 1,563 10th-grade students across five Southern California
      high schools. Measures of online and offline peer influences were computed and
      assessed using fixed-effects models. RESULTS: The frequency of adolescent SNS use
      and the number of their closest friends on the same SNSs were not significantly
      associated with risk behaviors. However, exposure to friends' online pictures of
      partying or drinking was significantly associated with both smoking (beta = .11,
      p < .001) and alcohol use (beta = .06, p < .05). Whereas adolescents with
      drinking friends had higher risk levels for drinking, adolescents without
      drinking friends were more likely to be affected by higher exposure to risky
      online pictures (beta = -.10, p < .05). Myspace and Facebook had demographically
      distinct user characteristics and differential effects on risk behaviors.
      CONCLUSIONS: Exposure to risky online content had a direct impact on adolescents'
      risk behaviors and significantly interacted with risk behaviors of their friends.
      These results provide evidence that friends' online behaviors should be
      considered a viable source of peer influence and that increased efforts should
      focus on educating adolescents on the negative effects of risky online displays.

PMID- 24012066
TI  - The effects of acute sleep restriction on adolescents' pedestrian safety in a
      virtual environment.
AB  - PURPOSE: Over 8,000 American adolescents ages 14-15 years require medical
      attention owing to pedestrian injury annually. Cognitive factors contributing to
      pedestrian safety include reaction time, impulsivity, risk taking, attention, and
      decision making. These characteristics are also influenced by sleep restriction.
      Experts recommend that adolescents obtain 8.5 hours of uninterrupted sleep each
      night, but most American adolescents do not. Inadequate sleep may place
      adolescents at risk for pedestrian injury. METHODS: Using a within-subjects
      design, 55 14- and 15-year-olds engaged in a virtual reality pedestrian
      environment under two conditions, scheduled a week apart: sleep-restricted (4
      hours' sleep the previous night) and adequate sleep (8.5 hours). Sleep was
      assessed using actigraphy and pedestrian behavior via four outcome measures: time
      to initiate crossing, time before contact with vehicle while crossing, virtual
      hits or close calls and attention to traffic (looks left and right). RESULTS:
      While acutely sleep restricted, adolescents took more time to initiate pedestrian
      crossings, crossed with less time before contact with vehicles, experienced more
      virtual hits or close calls, and looked left and right more often compared with
      when adequately rested. Results were maintained after controlling for age,
      gender, ethnicity, and average total sleep duration before each condition.
      CONCLUSIONS: Adolescent pedestrian behavior in the simulated virtual environment
      was markedly different, and generally more risky, when acutely sleep restricted
      compared with adequately rested. Inadequate sleep may influence cognitive
      functioning to the extent that pedestrian safety is jeopardized among adolescents
      capable of crossing streets safely when rested. Policy decisions might be
      educated by these results.

PMID- 24012067
TI  - Parental support and mental health among transgender adolescents.
AB  - PURPOSE: Family support is protective against health risks in sexual minority
      individuals. However, few studies have focused specifically on transgender youth,
      who often experience rejection, marginalization, and victimization that place
      them at risk for poor mental health. This study investigated the relationships
      among parental support, quality of life, and depression in transgender
      adolescents. METHODS: A total of 66 transgender youth presenting for care at
      Children's Hospital Los Angeles completed a survey assessing parental support
      (defined as help, advice, and confidante support), quality of life, and
      depression. Regression analyses assessed the associations between parental
      support and mental health outcomes. RESULTS: Parental support was significantly
      associated with higher life satisfaction, lower perceived burden of being
      transgender, and fewer depressive symptoms. CONCLUSIONS: Parental support is
      associated with higher quality of life and is protective against depression in
      transgender adolescents. Interventions that promote parental support may
      significantly affect the mental health of transgender youth.

PMID- 24012068
TI  - Dynamic indices of methamphetamine dependence and HIV infection predict
      fluctuations in affective distress: a five-year longitudinal analysis.
AB  - BACKGROUND: Methamphetamine (METH) use and human immunodeficiency virus (HIV)
      infection are highly comorbid, and both are associated with increased prevalence
      of affective distress. Delineating the trajectory of affective distress in the
      context of METH dependence and HIV infection is important given the implications
      for everyday functional impairment, adverse health behaviors, and increased risk
      for adverse health outcomes. METHODS: We conducted a five-year longitudinal
      investigation involving 133 METH-dependent (74 HIV seropositive) and 163 non-METH
      dependent (90 HIV seropositive) persons to examine both long-standing patterns
      and transient changes in affective distress. Mixed-effect regression models with
      random subject-specific slopes and intercepts evaluated the effect of METH
      dependence, HIV serostatus, and related variables on affective distress, as
      measured by the Profile of Mood States. RESULTS: Transient changes in affective
      distress were found to be greater among those with a diagnosis of current MDD,
      briefer durations of abstinence from METH, and higher quantity of METH consumed.
      Weak associations were observed among static (time-independent predictors)
      covariates and long-standing patterns in affective distress. LIMITATIONS: Study
      lacked data pertaining to the participants' involvement in METH treatment and
      relied on respondent-driven sampling. CONCLUSIONS: Our longitudinal investigation
      of the trajectory of affective distress indicated that specific and dynamic
      indices of current METH use were associated with greater transient changes in
      mood. In the evaluation and treatment of affective distress, recency and quantity
      of current METH use are important to consider given their association with
      heightened affective distress and mood instability over time.

PMID- 24012069
TI  - War-related trauma exposure and multiple risk behaviors among school-going
      adolescents in Northern Uganda: the mediating role of depression symptoms.
AB  - BACKGROUND: The relationship between war-related trauma exposure, depressive
      symptoms and multiple risk behaviors among adolescents is less clear in sub
      Saharan Africa. METHODS: We analyzed data collected from a sample of school-going
      adolescents four years postwar. Participants completed interviews assessing
      various risk behaviors defined by the Youth Self Report (YSR) and a sexual risk
      behavior survey, and were screened for post-traumatic stress, anxiety and
      depression symptoms based on the Impact of Events Scale Revised (IESR) and
      Hopkins Symptom Checklist for Adolescents (HSCL-37A) respectively. Multivariate
      logistic regression was used to assess factors independently associated with
      multiple risk behaviors. The logistic regression model of Baron and Kenny (1986)
      was used to evaluate the mediating role of depression in the relationship between
      stressful war events and multiple risk behaviors. RESULTS: Of 551 participants,
      139 (25%) reported multiple (three or more) risk behaviors in the past year. In
      the multivariate analyses, depression symptoms remained uniquely associated with
      multiple risk behavior after adjusting for potential confounders including socio
      demographic characteristics, war-related trauma exposure variables, anxiety and
      post-traumatic stress symptoms. In mediation analysis, depression symptoms
      mediated the associations between stressful war events and multiple risk
      behaviors. LIMITATIONS: The psychometric properties of the questionnaires used in
      this study are not well established in war affected African samples thus ethno
      cultural variation may decrease the validity of our measures. CONCLUSIONS:
      Adolescents with depression may be at a greater risk of increased engagement in
      multiple risk behaviors. Culturally sensitive and integrated interventions to
      treat and prevent depression among adolescents in post-conflict settings are
      urgently needed.

PMID- 24012070
TI  - A longitudinal examination of alcohol, marijuana, and cigarette perceived norms
      among middle school adolescents.
AB  - BACKGROUND: Adolescents tend to overestimate the prevalence of substance use
      among their peers and these perceived norms are associated with their current and
      future use. However, little is known about how perceived norms change over time
      during middle school, a developmental period when adolescents are at-risk for
      initiating substance use. METHOD: We examined changes in perceived norms of
      alcohol, marijuana, and cigarettes over a two-year period among a large and
      diverse sample of 6th and 7th grade youth (N=6097; 50.1% female; 54% Hispanic).
      Participants completed a baseline survey and two subsequent annual surveys.
      Participants estimated the percentage of their peers they believed used each
      substance, as well as indicated levels of personal use, offers to use from peers,
      and exposure to peers who were using each substance. RESULTS: Perceived norms of
      all three substances increased over time. Increases were somewhat attenuated when
      controlling for demographic factors, personal use, and peer factors, but remained
      significant. Female adolescents and those reporting non-Hispanic White ethnicity
      experienced the greatest increase in perceived norms over time. CONCLUSION:
      Normative perceptions of substance use increase greatly during the middle school
      years, an effect which cannot be fully explained by demographics, personal use,
      or peer factors. Given that perceived norms are often associated with personal
      use, early interventions with middle school youth are warranted to prevent the
      growth of these influential factors during this developmental period.

PMID- 24012071
TI  - The effect of nucleotomy on facet joint loading - a porcine in vitro study.
AB  - BACKGROUND: Lumbar facet joints have been cited as a possible origin of low-back
      pain. A relationship between disc height decrease and facet joint degeneration
      has been reported. Facet joint degeneration may also be triggered by nucleotomy,
      performed on prolapsed discs, which might change the natural load sharing between
      the anterior and posterior structures of the spine. In this study load bearing of
      the facet joints was compared between natural and nucleotomised spinal segments.
      METHODS: Nine porcine lumbar motion segments were tested quasi-statically in +/
      1.5 degrees  extension-flexion under 700 N constant compression loading. The
      kinematics of the spinal segments were recorded as a response to the applied
      load. These kinematics were subsequently applied to the segments with the
      ligaments and disc sequentially removed and the reaction forces measured. This
      was performed in samples with and without nucleotomy. Comparison of the reaction
      forces allowed a direct comparison between healthy and pathological force
      transmission over the facet joints. Load sharing was related to the proportion of
      removed nucleus. FINDINGS: The proportion of applied compression force supported
      by the facets increased from a mean of 40.7% (standard deviation, SD 10.0%) to
      82.0% (SD 7.2%) after nucleotomy averaged over the entire extension-flexion
      regime. No correlation was observed between facet loading and the proportion of
      the nucleus removed. INTERPRETATION: Increased facet loading after nucleotomy
      might cause greater cartilage wear, which may be related to facet joint
      degeneration. The independence of facet loading on the proportion of nucleus
      removed might be due to a complete pressure loss once the annulus is incised.

PMID- 24012074
TI  - Affective disorders and psychosis in youth.
AB  - The significance of psychosis has yet to be fully understood and research is
      complicated because psychosis is often a state rather than trait occurrence. In
      youth, psychoticlike phenomena are common. Rates of lifetime psychotic symptoms
      are higher than rates of psychosis during a current episode of mania or
      depression, at least in youth. Rates vary widely between studies. Hallucinations
      are also more common than delusions in youth. Psychotic phenomena can be mood
      congruent or incongruent. A good mental status examination requires close
      questioning. There are several interviews that structure how questions are asked,
      and rating scales that help anchor severity. 

PMID- 24012072
TI  - Childhood onset schizophrenia and early onset schizophrenia spectrum disorders.
AB  - The clinical severity, impact on development, and poor prognosis of childhood
      onset schizophrenia may represent a more homogeneous group. Positive symptoms in
      children are necessary for the diagnosis and hallucinations are more often
      multimodal. In healthy children and children with a variety of other psychiatric
      illnesses, hallucinations are not uncommon and diagnosis should not be based on
      these alone. Childhood onset schizophrenia is an extraordinarily rare illness
      that is poorly understood but seems continuous with the adult onset disorder.
      Once a diagnosis is affirmed, aggressive medication treatment combined with
      family education and individual counseling may defer further deterioration. 

PMID- 24012073
TI  - The prodrome and clinical risk for psychotic disorders.
AB  - The psychosis prodrome offers great promise for identifying neural mechanisms
      involved in psychotic disorders and offers an opportunity to implement empirical
      interventions to delay, and ultimately ameliorate, illness onset. This article
      summarizes the literature on individuals in the putatively prodromal phase of
      psychosis/deemed at clinical high risk (CHR) for psychosis onset. Standardized
      measurement and manifestation of the CHR syndromes are discussed, followed by
      empirical findings that highlight the psychological deficits and biological
      abnormalities seen in CHR syndromes and psychotic disorders. Current
      controversies surrounding the diagnosis of CHR syndromes and issues related to
      the treatment of CHR individuals are also presented. 

PMID- 24012075
TI  - Congenital and acquired disorders presenting as psychosis in children and young
      adults.
AB  - A review of the published literature found 60 congenital and acquired disorders
      with symptoms that include psychosis in youth. The prevalence, workup, genetics,
      and associated neuropsychiatric features of each disorder are described. Eighteen
      disorders (30%) have distinct phenotypes (doorway diagnoses); 18 disorders (30%)
      are associated with intellectual disability; and 43 disorders (72%) have
      prominent neurologic signs. Thirty-one disorders (52%) can present without such
      distinct characteristics, and are thus more easily overlooked. A systematic and
      cost-effective differential diagnostic approach based on estimated prevalence and
      most prominent associated signs is recommended. 

PMID- 24012076
TI  - "Autism-plus" spectrum disorders: intersection with psychosis and the
      schizophrenia spectrum.
AB  - Patients are often encountered clinically who have autism spectrum disorders
      (ASD) and also have symptoms suggestive of a comorbid psychotic disorder. A
      careful assessment for the presence of comorbid disorders is important. However,
      the core deficits seen in ASD, in social reciprocity, communication, and
      restricted behaviors and interests, can be mistaken for psychosis. Also, there is
      a subset of patients who present with a complex neurodevelopmental disorder with
      impairments that cross diagnostic categories. This article reviews the
      connections between ASD and psychosis, and highlights the key points to consider
      in patients who present with these "autism-plus" disorders. 

PMID- 24012077
TI  - Childhood trauma and psychosis.
AB  - Childhood trauma is a common occurrence and has been associated with psychosis
      and suggested as a risk factor leading to psychosis and schizophrenia in
      adulthood. This article introduces the scope of the problem and discusses the
      evidence for causal relationships between childhood adversities and increased
      risk for psychosis. The relationship between specific types of trauma and their
      association with specific psychotic symptoms is described, as well as the
      manifestations of co-occurring trauma effects and psychosis in adolescents.
      Clinical presentations and the use of diagnostic instruments, diagnostic
      comorbidities, and evidence-based psychotherapeutic interventions to treat
      effects of trauma in youth with psychotic illnesses are discussed. 

PMID- 24012078
TI  - Substance abuse and psychosis.
AB  - This article reviews the literature for the most pressing diagnostic and
      treatment challenges faced in working with adolescents. Diagnosing the treatment
      interventions required for this population involve psychoeducation, engagement of
      the patient and family in the treatment process, and use of antipsychotic
      medications. Cannabis may be a causal risk factor in psychotic illness, and data
      support recommendations to reduce or cease cannabis use in this population.
      Treatment strategies are discussed that are effective in adult patients and that
      may be efficacious for youth to abstain from substances after the resolution of
      psychotic symptoms. 

PMID- 24012079
TI  - Diagnosis and evaluation of hallucinations and other psychotic symptoms in
      children and adolescents.
AB  - Recognizing positive psychotic symptoms and their diagnostic context in youth is
      challenging. A large minority say they "hear things others do not hear," though
      they seldom present with complaints of hallucinations or delusions. Few have
      schizophrenia spectrum disorder, but many have other psychiatric disorders.
      Frequently, they have psychotic symptoms for an extended period before diagnosis.
      Clinicians should understand psychotic symptoms and their differential diagnoses.
      This article reviews the epidemiology, associated diagnoses, and prognosis of
      hallucinations and delusions in youth. Strategies for optimizing the clinical
      diagnostic interview, appropriate laboratory tests, indications for psychological
      testing, and rating scales are reviewed. 

PMID- 24012080
TI  - Genetics of childhood-onset schizophrenia.
AB  - Schizophrenia is a heritable disorder. The genetic architecture of schizophrenia
      is complex and heterogeneous. This article discusses genetic studies of childhood
      onset schizophrenia (COS) and compares findings in familial aggregation, common
      allele, and rare allele studies of COS with those for adult-onset schizophrenia
      (AOS). COS seems to be a rare variant of AOS with greater familial aggregation of
      schizophrenia spectrum disorders and higher occurrence of rare allelic variants.
      The usefulness of genetic screening for diagnosis and individualized treatment is
      limited; however, identifying common pathways through which multiple genes
      adversely affect neural systems offers great promise toward developing novel
      pharmacologic interventions. 

PMID- 24012082
TI  - Neurocognition in early-onset schizophrenia.
AB  - Cognitive impairment is recognized as a central feature of schizophrenia. Early
      onset schizophrenia (EOS) represents a more severe variant of the disorder
      associated with onset in childhood or adolescence. Examination of the cognitive
      abnormalities of EOS offers the opportunity to explore how disease-related
      mechanisms may affect facets of cognitive development. This article summarizes
      and synthesizes available data with regards to the profile of cognitive
      impairments in EOS, their severity, and their evolution over the course of the
      disorder. 

PMID- 24012083
TI  - Psychopharmacologic treatment of psychosis in children and adolescents: efficacy
      and management.
AB  - The efficacy of antipsychotic use in children and adolescents with psychosis has
      been shown in an increasing number of randomized controlled trials. Chronic use
      of second-generation and third-generation antipsychotics has the potential for
      significant side effects, especially metabolic syndrome. A review of the
      literature on side effect profiles of antipsychotic medications used in children
      and adolescents is provided to help clinicians develop treatment plans for their
      patients. Clozapine has the best efficacy of all antipsychotic medications in
      adults as well as children and adolescents who are treatment resistant. Guidance
      is provided for the management of clozapine side effects. 

PMID- 24012084
TI  - Community rehabilitation and psychosocial interventions for psychotic disorders
      in youth.
AB  - During recovery, young people with psychosis need attention paid not only to
      their psychotic symptoms but also to the areas of functioning that restrict their
      capacity to live a fulfilled life in the community. Despite improvements in
      medications and psychological therapies, people with psychosis still have poor
      outcomes in functional domains such as vocation, physical health, housing, and
      imprisonment. This article reviews 2 of these areas: vocational functioning and
      physical health. It examines the extent of each of these issues, provides
      guidance as to what evidence there exists on which to base interventions, and
      describes such evidence. 

PMID- 24012085
TI  - Psychotic disorders in youth: diagnostic and treatment challenges.

PMID- 24012081
TI  - Gray matter alterations in schizophrenia high-risk youth and early-onset
      schizophrenia: a review of structural MRI findings.
AB  - This article reviews the literature on structural magnetic resonance imaging
      findings in pediatric and young adult populations at clinical or genetic high
      risk for schizophrenia and early-onset schizophrenia. The implications of this
      research are discussed for understanding the pathophysiology of schizophrenia and
      for early intervention strategies. The evidence linking brain structural changes
      in prepsychosis development and early-onset schizophrenia with disruptions of
      normal neurodevelopmental processes during childhood or adolescence is described.
      Future directions are outlined for research to address knowledge gaps regarding
      the neurobiological basis of brain structural abnormalities in schizophrenia and
      to improve the usefulness of these abnormalities for preventative interventions. 

PMID- 24012086
TI  - Effect of simultaneous supplementation of vitamin A and iron on diarrheal and
      respiratory tract infection in preschool children in Chengdu City, China.
AB  - OBJECTIVE: The goal of this study was to investigate whether vitamin A combined
      with iron supplementation for preschool children resulted in improved changes in
      children's infectious morbidity. METHOD: In this randomized placebo-controlled
      and blinded field intervention trial, totally 445 preschoolers, ages 3 to 6 y
      old, were randomly selected. All children were randomly divided into four groups:
      vitamin A supplement-only group (group I), iron supplement-only group (group II),
      vitamin A and iron supplement group (group III), and no vitamin A and ferrous
      sulfate as placebo-control (group IV) for 6 mo. The morbidity of diarrhea and
      respiratory infections, were collected during supplementation. RESULTS: There was
      evidence of the lowest incidence rate of respiratory-related illnesses and fewest
      symptoms of runny nose, cough, and fever for children in group III compared with
      children in groups I, II and IV (P < 0.05). Moreover, despite the undistinguished
      incidence rate of vomiting, nausea, and stomach pain, the rate of diarrhea
      related illness was significantly lower for children in group III than for those
      in the other three groups. CONCLUSION: The beneficial affects on infectious
      morbidity over 6 mo, highlight the potential of vitamin A plus an iron supplement
      for preschool-aged children.

PMID- 24012087
TI  - Negative energy balance secondary to inadequate dietary intake of patients on the
      waiting list for liver transplantation.
AB  - OBJECTIVES: The aim of this study was to evaluate the energy balance (EB) of
      patients on the waiting list for liver transplantation, using total energy
      expenditure (TEE) assessment and total caloric intake (TCI). METHODS: We analyzed
      nutrient adequacy and factors associated with it. EB was obtained by subtracting
      the TCI (obtained by 3-d food record) from TEE, which was measured as resting
      energy expenditure and physical activity factor calculation. Socioeconomic and
      clinical data also were evaluated. Univariate and multiple linear regressions
      were used (P < 0.05). Seventy-three patients were included. RESULTS: The TEE was
      2318.5 kcal, and the TCI was 1485.1 kcal, with 81.6% of patients presenting with
      negative EB. There was no significant association between TCI and socioeconomic
      variables, medications, and encephalopathy (P > 0.05). Women, less-educated
      patients, those with ascites, and those who were malnourished presented with
      lower TCI (P < 0.05). Severity of disease, by Child-Pugh and Model for End-Stage
      Liver Disease scores were associated with EB (P < 0.05). Child-Pugh remained
      significant after multivariate analyses. Energy inadequacy was observed in 91.8%
      of patients, and protein inadequacy in 72.6% of patients. Polyunsaturated fatty
      acid (64.4%) and monounsaturated fatty acid (91.8%) and fiber (94.5%)
      inadequacies also were high. The percentage of adequate intake was less than 10%
      for vitamins B5 and D, calcium, folic acid, and potassium, and higher percentages
      of adequate intake (>80%) were found for iron and vitamins B1 and B12. Moreover,
      54.8% and 16.4% of the patients had excessive sodium and cholesterol intakes,
      respectively. CONCLUSION: Negative EB was highly prevalent among patients on the
      waiting list for liver transplantation, and was associated with the severity of
      liver disease. Negative EB was primarily affected by low food intake. The food
      intake data were characterized by low overall energy and protein intake and
      inadequate composition of the patient's diet plan, which tended to be
      characterized by specific nutrient deficiencies and excesses.

PMID- 24012089
TI  - Professional liability claims in vascular surgery practice.
AB  - BACKGROUND: Patient safety is a major concern worldwide, but particularly high
      rates of adverse events are reported in the surgery setting. Angiology and
      vascular surgery is of special interest due to the complexity of the pathologies
      involved and the esthetic component of some of its procedures. In this study we
      identified the most frequent factors that apply to vascular surgery claims to
      determine areas of special risk in vascular surgery, with an aim to improve
      patient safety. METHODS: We performed a retrospective and descriptive study of
      the claims pertaining to vascular surgery from the database of the Service of
      Professional Liability (SRP) of the Official College of Physicians of Barcelona.
      The time frame of data collection was from 1986 to 2009. We analyzed both the
      clinical and legal characteristics of the cases. RESULTS: Of the total of 6952
      registered claims during the 23-year period, 91 (1.3%) were related to the
      practice of vascular surgery. Of these, 53.8% were related to venous pathology
      and 46.1% to arterial pathology. Neurologic damage was the main motive for claims
      (15.3%), followed by thromboembolic disease (14.2%), burns as a result of
      cosmetic treatment (12%), and amputation (10.9%). The neurologic damage in
      relation to vein pathology registered the greatest proportion of cases with
      professional liability (30.8%), followed by burns (19.2%), forgotten gauze
      (11.5%), and amputations (11.5%). CONCLUSIONS: Angiology and vascular surgery
      does not seem to be a specialty with a high risk for claims, but complications,
      such as thromboembolic disease and neurologic damage after varicose vein
      intervention, do occur and deserve special attention so improvements can be made
      to patient safety.

PMID- 24012088
TI  - Consumption of a low-carbohydrate and high-fat diet (the ketogenic diet)
      exaggerates biotin deficiency in mice.
AB  - OBJECTIVE: Biotin is a water-soluble vitamin that acts as a cofactor for several
      carboxylases. The ketogenic diet, a low-carbohydrate, high-fat diet, is used to
      treat drug-resistant epilepsy and promote weight loss. In Japan, the infant
      version of the ketogenic diet is known as the "ketone formula." However, as the
      special infant formulas used in Japan, including the ketone formula, do not
      contain sufficient amounts of biotin, biotin deficiency can develop in infants
      who consume the ketone formula. Therefore, the aim of this study was to evaluate
      the effects of the ketogenic diet on biotin status in mice. METHODS: Male mice (N
      = 32) were divided into the following groups: control diet group, biotin
      deficient (BD) diet group, ketogenic control diet group, and ketogenic biotin
      deficient (KBD) diet group. Eight mice were used in each group. RESULTS: At 9 wk,
      the typical symptoms of biotin deficiency such as hair loss and dermatitis had
      only developed in the KBD diet group. The total protein expression level of
      biotin-dependent carboxylases and the total tissue biotin content were
      significantly decreased in the KBD and BD diet groups. However, these changes
      were more severe in the KBD diet group. CONCLUSION: These findings demonstrated
      that the ketogenic diet increases biotin bioavailability and consumption, and
      hence, promotes energy production by gluconeogenesis and branched-chain amino
      acid metabolism, which results in exaggerated biotin deficiency in biotin
      deficient mice. Therefore, biotin supplementation is important for mice that
      consume the ketogenic diet. It is suggested that individuals that consume the
      ketogenic diet have an increased biotin requirement.

PMID- 24012090
TI  - Independent factors predicting early lower limb intra-arterial thrombolysis
      failure.
AB  - BACKGROUND: Risk factors for early catheter-directed intra-arterial thrombolysis
      failure in acute lower limb ischemia remain unclear. METHODS: One hundred forty
      nine limbs with acute artery or bypass graft thrombosis underwent catheter
      directed thrombolysis (maximum of 48 hours). A retrospective data analysis was
      carried out to assess possible risk factors for early, 30-day treatment failure.
      RESULTS: Seventy-nine men (53%) and 70 women (47%) with a median age of 70 (range
      32-93) years were treated. Treatment outcomes were determined as success (N =
      115, 77%) or failure (N = 34, 23%). The failure criteria comprised rapid
      progression of ischemia (N = 4, 2.7%) and major bleeding complications (N = 2,
      1.3%), both requiring thrombolysis termination and surgery. Inability to reopen
      native arteries/grafts (N = 10, 6.7%), run-off vessels (N = 10, 6.7%), in
      hospital death (N = 4, 2.7%), the need for major amputation (N = 13, 8.7%), and
      reocclusions (N = 5, 3.4%) within the 30-day follow-up period were also
      considered as failures. Multivariate analysis of the risk factors' impact on the
      success of thrombolysis revealed such independent parameters as
      hypercholesterolemia (OR 0.16, 95% CI 0.06-0.42, P < 0.0001), previous bypass
      grafting of the ipsilateral limb (OR 0.18, 95% CI 0.06-0.53, P = 0.002), and
      duration of ischemia prior to the initiation of thrombolysis (OR 0.95, 95% CI
      0.91-0.99, P = 0.009, per day). CONCLUSION: According to our results, factors
      independently predicting early failure include hypercholesterolemia, previous
      bypass grafting, and a delay in treatment initiation. Moreover, catheter-directed
      intra-arterial thrombolysis can be considered safe and effective in the treatment
      of acute lower limb ischemia.

PMID- 24012091
TI  - Technique for using pedicled latissimus dorsi muscle flaps to wrap prosthetic
      grafts in an infected thoracic aorta.
AB  - In this report we describe a special method of using a pedicled latissimus dorsi
      muscle flap for a mycotic aneurysm. The method involves wrapping the flap around
      a prosthetic graft. Using this method, an in situ graft, which replaces an
      aneurysm, can help to avoid recurrence of local infection. 

PMID- 24012092
TI  - Novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one derivatives as potential
      inhibitors of chorismate mutase.
AB  - A series of novel alkynyl substituted 3,4-dihydropyrimidin-2(1H)-one (DHPM)
      derivatives were designed, synthesized and evaluated in vitro as potential
      inhibitors of chorismate mutase (CM). All these compounds were prepared via a
      multi-component reaction (MCR) involving sequential I2-mediated Biginelli
      reaction followed by Cu-free Sonogashira coupling. Some of them showed promising
      inhibitory activities when tested at 30MUM. One compound showed dose dependent
      inhibition of CM with IC50 value of 14.76+/-0.54MUM indicating o-alkynylphenyl
      substituted DHPM as a new scaffold for the discovery of promising inhibitors of
      CM. 

PMID- 24012093
TI  - Indigenous cellulolytic and hemicellulolytic bacteria enhanced rapid co
      composting of lignocellulose oil palm empty fruit bunch with palm oil mill
      effluent anaerobic sludge.
AB  - The composting of lignocellulosic oil palm empty fruit bunch (OPEFB) with
      continuous addition of palm oil mill (POME) anaerobic sludge which contained
      nutrients and indigenous microbes was studied. In comparison to the conventional
      OPEFB composting which took 60-90 days, the rapid composting in this study can be
      completed in 40 days with final C/N ratio of 12.4 and nitrogen (2.5%), phosphorus
      (1.4%), and potassium (2.8%), respectively. Twenty-seven cellulolytic bacterial
      strains of which 23 strains were closely related to Bacillus subtilis, Bacillus
      firmus, Thermobifida fusca, Thermomonospora spp., Cellulomonas sp., Ureibacillus
      thermosphaericus, Paenibacillus barengoltzii, Paenibacillus campinasensis,
      Geobacillus thermodenitrificans, Pseudoxanthomonas byssovorax which were known as
      lignocellulose degrading bacteria and commonly involved in lignocellulose
      degradation. Four isolated strains related to Exiguobacterium acetylicum and
      Rhizobium sp., with cellulolytic and hemicellulolytic activities. The rapid
      composting period achieved in this study can thus be attributed to the naturally
      occurring cellulolytic and hemicellulolytic strains identified.

PMID- 24012094
TI  - The environmental sustainability of microalgae as feed for aquaculture: a life
      cycle perspective.
AB  - The environmental sustainability of microalgae production for aquaculture
      purposes was analyzed using exergy analysis (EA) and life cycle assessment (LCA).
      A production process (pilot 2012, 240 m(2)) was assessed and compared with two
      upscaling scenarios (pilot 2013, 1320 m(2) and first production scale 2015, 2.5
      ha). The EA at process level revealed that drying and cultivation had the lowest
      efficiencies. The LCA showed an improvement in resource efficiency after
      upscaling: 55.5 MJ(ex,CEENE)/MJ(ex) DW biomass was extracted from nature in 2012,
      which was reduced to 21.6 and 2.46 MJ(ex,CEENE)/MJ(ex) DW in the hypothetical
      2013 and 2015 scenarios, respectively. Upscaling caused the carbon footprint to
      decline by factor 20 (0.09 kg CO2,eq/MJ(ex) DW in 2015). In the upscaling
      scenarios, microalgae production for aquaculture purposes appeared to be more
      sustainable in resource use than a reference fish feed (7.70 MJ(ex,CEENE) and
      0.05 kg CO2,eq per MJ(ex) DW).

PMID- 24012095
TI  - Chemoenzymatic synthesis of alpha-L-rhamnosides using recombinant alpha-L
      rhamnosidase from Aspergillus terreus.
AB  - This study describes an efficient, large scale fermentation of a recombinant
      alpha-L-rhamnosidase originating from Aspergillus terreus. High-cell-density
      Pichia pastoris fermentation resulted in yields up to 627 U/L/h. The recombinant
      enzyme was used for the reverse rhamnosylation of various small organic
      compounds. A full factorial experimental design setup was applied to identify the
      importance of temperature, substrate concentrations, solvent type and
      concentration as well as the acidity of the reaction mixture. Careful
      optimization of these parameters allowed the synthesis of a range of alpha-L
      rhamnosides among which cyclohexyl alpha-L-rhamnopyranoside, anisyl alpha-L
      rhamnopyranoside and 2-phenylethyl alpha-L-rhamnopyranoside. In addition, alpha-L
      rhamnosylation of phenolic hydroxyls in phenols such as hydroquinone, resorcinol,
      catechol and phenol was observed, which is a rather unique reaction catalyzed by
      glycosidases.

PMID- 24012096
TI  - Higher dose cervical 2% lidocaine gel for IUD insertion: a randomized controlled
      trial.
AB  - OBJECTIVE: To determine the effectiveness of 6 mL of 2% lidocaine cervical gel
      for pain during intrauterine device (IUD) insertion. STUDY DESIGN: This is a
      randomized double-blind placebo controlled trial of 6 mL of 2% lidocaine gel for
      IUD insertion pain among first-time IUD users. No other analgesia other than the
      study intervention was provided. The study was conducted at a university-based
      obstetrics and gynecology clinic. The primary outcome, pain during IUD insertion
      on a 0 to 100-mm visual analog scale, was analyzed using the t test. RESULTS:
      Seventy-three women received placebo gel, and 72 women received 2% lidocaine gel.
      The groups had similar sociodemographic and clinical characteristics. Baseline
      pain scores with speculum insertion were no different between the two groups. The
      lidocaine group reported a mean pain score with tenaculum placement of 37.5
      (median: 39) compared to the placebo group of 41.6 (median: 37) (p=.4).
      Similarly, pain with IUD insertion was no different with a mean pain score of
      35.2 (median: 34) in the lidocaine group and 36.7 (median 36) in the placebo
      group (p=.8). CONCLUSIONS: Two percent lidocaine gel placed on the anterior lip
      of the cervix and at the internal os did not reduce pain with tenaculum placement
      and IUD insertion compared to placebo gel. IMPLICATIONS: Among first-time IUD
      users, including both nulliparous and multiparous women, 6 mL of 2% lidocaine gel
      placed on the anterior lip of the cervix and at the internal os for 3 min did not
      reduce pain with tenaculum placement and IUD insertion compared to placebo gel.

PMID- 24012097
TI  - Adherence to hysterosalpingogram appointments following hysteroscopic
      sterilization among low-income women.
AB  - BACKGROUND: The few studies on post-Essure hysterosalpingogram (HSG) adherence
      rates show inconsistent results. This study examined associations between
      sociodemographic variables not examined in prior studies and HSG adherence among
      low-income women. STUDY DESIGN: Medical records of 286 women who underwent
      sterilization between August 31, 2005, and September 30, 2011, were reviewed. chi
      Square and Mann-Whitney U tests were used to determine variable associations with
      HSG adherence. RESULTS: The adherence rate for the first HSG was 85.0% (243/286).
      Variables associated with adherence were lower education level (p=.01), not
      working outside the home (p=.04), being married (p<.0001), lower gravidity
      (p=.03), fewer lifetime number of sexual partners (p<.0001), no sexually
      transmitted infection history (p<.01), Hispanic ethnicity (p<.0001), Spanish as a
      primary language (p<.0001) and living farther from the clinic (p<.01).
      CONCLUSIONS: This study demonstrates that achieving high rates of adherence with
      the recommended HSG following Essure placement is feasible among low income
      populations. Furthermore, not speaking English or having to commute a far
      distance to the clinic do not appear to be barriers. This is encouraging
      considering the importance of this test to confirm tubal occlusion.

PMID- 24012098
TI  - Sorafenib and bevacizumab combination targeted therapy in advanced neuroendocrine
      tumour: a phase II study of Spanish Neuroendocrine Tumour Group (GETNE0801).
AB  - BACKGROUND: Sorafenib and bevacizumab as single agents have shown efficacy and
      acceptable toxicity in NETs phase II trials. Sorafenib and bevacizumab
      combination has shown manageable toxicity in phase I trials in solid tumours. The
      purpose of this study was to evaluate the safety and efficacy of the combination
      of sorafenib and bevacizumab in patients with advanced neuroendocrine tumours.
      METHODS: Open-label, uncontrolled, multicenter, phase II clinical trial.
      ELIGIBILITY CRITERIA: age >=18 years, histologically confirmed measurable
      advanced NETs; 1 prior chemotherapy allowed; ECOG-PS 0-2. Patients were treated
      during 6 months and followed up for an additional 6 months. TREATMENT: sorafenib
      200mg bid (days 1-5 of each week) and bevacizumab 5mg/kg once every 2 weeks (day
      1, week 1). Tumour response was performed according to RECIST (v1.0) every 2
      months during the treatment period. Adverse events were graded according to CTCAE
      (v3.0). FINDINGS: 44 Patients enrolled, 59.1% men, median age 60 years (range 32
      76). 70.5% carcinoid tumours, 29.5% pancreatic tumour. Baseline target lesions
      mainly in the liver (86.4%). Global PFSR was 90.9% (91.7% carcinoid tumours and
      88.9% pancreatic tumours). Median PFS was 12.4 months, median TTP was 14.5
      months, ORR was 9.4% and DCR was 95.1%. Most common grade 3-4 toxicities:
      asthenia (11.4%) and hand-foot skin reaction (15.9%). INTERPRETATION: Sorafenib
      and bevacizumab combination showed clinical benefit but unfavourable safety
      results compared with drugs in monotherapy. Further development of this
      combination is not warranted and a sequential approach is recommended instead.

PMID- 24012099
TI  - Ovarian Brenner tumour: a morphologic and immunohistochemical analysis suggesting
      an origin from fallopian tube epithelium.
AB  - BACKGROUND: Brenner tumours (BTs), like other epithelial ovarian tumours, are
      thought to develop from the ovarian surface epithelium. AIM AND METHODS: We
      hypothesised that BTs arise from transitional metaplasia near the tuboperitoneal
      junction which, when embedded in the ovary as Walthard cell nests, may progress
      to BTs. The aim of this study was to validate this hypothesis by a morphologic
      and immunohistochemical (IHC) analysis. RESULTS: The IHC analysis revealed that
      fallopian tube secretory cells, transitional metaplasia, Walthard cell nests and
      the epithelial component of BTs shared a similar IHC profile, consistently
      expressing AKR1C3 (an enzyme involved in androgen biosynthesis) and androgen
      receptor, but not calretinin. The tumour stromal cells that immediately
      surrounded the epithelial nests showed strong expression of calretinin, inhibin
      and steroidogenic factor 1 (markers of steroidogenic cells) in the majority of
      BTs. Using a highly sensitive immunofluorescent staining method, we detected
      small groups of cilia in transitional metaplasia and Walthard cell nests,
      multifocal stretches of cilia and/or ciliated vacuoles in benign BTs and well
      developed cilia in atypical proliferative BTs. CONCLUSIONS: Our findings suggest
      a tubal origin of BTs through transitional metaplasia and Walthard cell nests,
      based on their anatomic proximity, similar IHC profile and the presence of cilia.
      In addition, we hypothesise a role of androgenic stimulation in the pathogenesis
      of BT, based on the IHC staining pattern of calretinin, inhibin and steroidogenic
      factor 1 expressed in the luteinised stromal cells surrounding the epithelial
      nests of the tumours, and AKR1C3 and androgen receptor expressed in both the
      epithelial and stromal components.

PMID- 24012100
TI  - Systemic diagnostic testing in patients with apparently isolated uveal coloboma.
AB  - PURPOSE: To investigate the frequency and types of systemic findings in patients
      with apparently isolated uveal coloboma. DESIGN: Cross-sectional observational
      study. METHODS: setting: Single-center ophthalmic genetics clinic. study
      population: Ninety-nine patients with uveal coloboma seen at the National Eye
      Institute. observational procedure: Results of audiology testing, echocardiogram,
      brain magnetic resonance imaging, renal ultrasound, and total spine radiographs.
      main outcome measure: Prevalence of abnormal findings on systemic testing.
      RESULTS: Uveal coloboma affected only the anterior segment in 8 patients, only
      the posterior segment in 23 patients, and both anterior and posterior segments in
      68 patients. Best-corrected visual acuity (BCVA) of eyes with coloboma was
      >=20/40 in 45% of eyes; 23% of eyes had BCVA of <=20/400. The majority of
      patients (74%) had good vision (>20/60) in at least 1 eye. Ten of the 19 patients
      (53%) who underwent echocardiography had abnormalities, with ventral septal
      defects being the most prevalent. Abnormal findings were observed in 5 of 72
      patients (7%) who had a renal ultrasound and in 5 of 29 patients (17%) who
      underwent a brain MRI. Audiology testing revealed abnormalities in 13 of 75
      patients (17%), and spine radiographs showed anomalies in 10 of 77 patients
      (13%). Most findings required no acute intervention. CONCLUSIONS: Although some
      patients with coloboma had evidence of extraocular abnormalities, the majority of
      findings on routine clinical examination did not require acute intervention, but
      some warranted follow-up. Results from the systemic evaluation of patients with
      coloboma should be interpreted with caution and in view of their clinical
      context.

PMID- 24012102
TI  - High insulin-like growth factor-1 in patients with bipolar I disorder: a trait
      marker?
AB  - OBJECTIVES: Neurotrophic factors exert substantial effects on the central nervous
      system. The present study investigates the roles of insulin-like growth factor-1
      (IGF-1), beta-nerve growth factor (beta-NGF), and brain-derived neurotrophic
      factor (BDNF) in bipolar disorder. METHODS: Baseline levels of culture-stimulated
      IGF-1, beta-NGF, and BDNF were compared in 116 patients with bipolar I disorder
      and 123 healthy controls. Neurotrophic factors were also compared in patients
      before and after 6 weeks of pharmacotherapy. A multivariate logistic regression
      analysis was used to investigate the influence of the neurotrophic factors
      analyzed in quartile form, in relation to confounding variables, such as age,
      sex, and body mass index. RESULTS: IGF-1 was significantly higher in patients
      (mean=514.57, SD=259.78) than in healthy controls (mean=316.82, SD=270.00,
      p<0.0001) at baseline. Furthermore, higher levels of IGF-1 substantially
      increased the risk for bipolar I disorder. IGF-1 level was not significantly
      changed at 6-weeks (mean=506.41, SD=313.66). No changes in BDNF or beta-NGF-1
      levels were found following the 6-week treatment period. IGF-1 and beta-NGF were
      negatively correlated in healthy controls, but not in patients. Severity of manic
      symptoms was not associated with any of the neurotrophic factors. LIMITATIONS: We
      did not measure cortisol, growth hormone, or IGF-1 receptors. This study is cross
      sectional in design. CONCLUSIONS: Elevated IGF-1 levels may be a trait marker for
      bipolar disorder. Further studies are needed to thoroughly investigate the role
      of IGF-1 in relation to other neuroendocrine factors and biological markers for
      bipolar disorder.

PMID- 24012101
TI  - The role of soluble P selectin in the diagnosis of venous thromboembolism.
AB  - INTRODUCTION: Soluble P selectin (sPsel), a member of the selectin family of cell
      adhesion receptors, has been proposed as a key molecule in hemostasis and
      thrombosis mediating platelet rolling, generating procoagulant microparticles and
      enhancing fibrin deposition. The aim of this study was to examine the role of
      sPsel in the diagnosis of venous thromboembolism (VTE). MATERIALS AND METHODS: We
      performed a systematic review and we used meta-analysis to synthesize data from
      published studies reporting sPsel levels in patients with i) VTE (deep venous
      thrombosis; DVT or DVT and pulmonary embolism; PE) and ii) DVT only. Pooled Odds
      Ratios (ORs) with 95% Confidence Intervals (CIs) were appropriately calculated
      among patients and controls. Diagnostic performance of sPsel was tested with
      pooled sensitivity, specificity, Diagnostic Odds Ratio (DOR) and summary receiver
      operator characteristic (SROC) curve. RESULTS: Eleven studies, comprising of 586
      VTE patients and 1,843 controls were deemed eligible. The sPsel was significantly
      increased after VTE (OR=2.89, 95%CI=2.31-3.61, p<0.001), or DVT only (OR=2.64,
      95%CI=1.95-3.56, p<0.001). Subgroup analysis evidenced that sPsel was also
      increased after VTE when evaluating only studies with patients that had no prior
      medical history (OR=2.88, 95%CI=1.98-4.19, p<0.001). Exclusion of studies
      including patients with solid organ tumor, HIV or lupus anticoagulants positive
      patients did not alter findings. Pooled sensitivity and specificity of sPsel was
      0.57 (95%CI=0.30-082, p<0.001) and 0.73 (95%CI=0.51-0.90, p<0.001), respectively
      and DOR was 4.31 (95%CI=2.22-8.37, p<0.01). SROC curve yielded in significant
      accuracy of sPsel performance (AUC=0.74, p=0.05). CONCLUSIONS: The sPsel was
      significantly elevated in patients with DVT, both uncomplicated and complicated
      with PE and presented with high levels of diagnostic performance. sPsel is a
      plasma biomarker that may help in the diagnosis of VTE.

PMID- 24012103
TI  - Association between OPCRIT dimensions and polymorphisms of HPA axis genes in
      bipolar disorder.
AB  - The aim of the study was to investigate the possible association between
      polymorphisms of HPA axis genes-CRHR1 (corticotrophin-releasing hormone
      receptor), NR3C1 (glucocorticoid receptor) and AVPR1B (arginine vasopressin
      receptor) and dimensions of bipolar disorder assessed by OPCRIT. We examined 560
      patients with diagnosis of bipolar disorder (n=457) and unipolar disorder
      (n=103). Diagnosis was established by SCID and OPCRIT. We found association
      between polymorphisms of AVPR1b gene and psychotic dimension and CRHR1
      polymorphisms and excitement and psychotic dimension. Our results suggest
      possible involvement of the AVPR1b and CRHR1 genes in the ethiology of psychotic
      features in the course of affective disorders, and possible involvement of CRHR1
      gene in the ethiology of bipolar disorder.

PMID- 24012104
TI  - Transcatheter closure of secundum atrial septal defects: results in patients with
      large and extreme defects.
AB  - BACKGROUND: Transcatheter closure of moderate sized atrial septal defects (ASD)
      has been demonstrated to be safe and effective. However, the feasibility of
      transcatheter closure of very large defects is less clear, particularly when an
      aortic rim of septal tissue is absent. METHODS: The study included patients
      referred for transcatheter ASD closure with maximal ASD diameter >= 20 mm at pre
      procedural transoesophageal echocardiography. Patients were grouped according to
      presence of moderately large (20-29 mm), very large (30-39 mm), or extremely
      large (>= 40 mm) ASD size. Procedural success was defined by successful device
      deployment and absence of complications. RESULTS: Forty-two patients (median age
      40 years, range 12-85 years, 76% female) were included in the study. The mean
      maximal ASD diameter was 29.0 +/- 7.4mm. Twenty-three patients had moderately
      large ASDs (23.0 +/- 2.8mm); 13 had very large ASDs (33.1 +/- 2.9 mm) and six had
      extremely large ASDs (41.3 +/- 1.6 mm). The aortic rim was absent in 22 patients,
      and present in 20 patients (4.7 +/- 2.9 mm). Transcatheter defect closure was
      successful in 36 of 42 patients (86%). Procedural success was 100% in the
      moderately large ASD group, 92% in the very large group but only 17% (one out of
      six) in the extremely large group. If patients with ASD >= 40 mm were excluded (n
      = 6), the overall success rate was 97%. A single complication (device
      dislodgement) occurred in a patient with a 42 mm defect and a deficient postero
      inferior rim. The presence or absence of an aortic rim of septum did not
      influence procedural success. CONCLUSION: The vast majority (97%) of large ASDs
      in the range 20-39 mm can be successfully closed percutaneously with a low or
      zero complication rate. However, procedural success is poor when attempting
      closure of extreme defects (>= 40 mm), regardless of whether an aortic rim of
      septal tissue or present or absent.

PMID- 24012105
TI  - Biochemical and molecular evidence of a Delta9 fatty acid desaturase from Ensifer
      meliloti 1021.
AB  - It has been reported that Ensifer meliloti presents a high proportion of
      monounsaturated fatty acids and has a putative desaturase gene designated as
      PhFAD12 (National Centre for Biotechnology Information), encoding a putative
      Delta12 desaturase-like protein. In this work, we report the desaturation
      capacity and characterisation of this gene encoding the putative fatty acid
      desaturase of E. meliloti 1021. This gene was also isolated from the rhizobial
      strain and overexpressed in Escherichia coli. Compared to a control, the
      expression of this gene in the transformed strain decreased the levels of
      palmitic and stearic acids, enhanced palmitoleic and cis-vaccenic levels, and
      allowed for the detection of oleic acid. E. coli overexpressing the putative
      desaturase gene was capable of desaturating palmitic and stearic acids to
      monounsaturated fatty acids, similarly to the rhizobial strain. Our studies show
      that AAK64726 encodes a Delta9 desaturase instead of a Delta12 desaturase as
      previously indicated. This work describes evidence for the presence of a
      desaturase-mediated mechanism in monounsaturated fatty acid synthesis in E.
      meliloti 1021, which is modified by high growth temperature. This mechanism
      supplements the anaerobic mechanism for unsaturated fatty acid synthesis. 

PMID- 24012106
TI  - Dynamic changes in brewing yeast cells in culture revealed by statistical
      analyses of yeast morphological data.
AB  - The vitality of brewing yeasts has been used to monitor their physiological state
      during fermentation. To investigate the fermentation process, we used the image
      processing software, CalMorph, which generates morphological data on yeast mother
      cells and bud shape, nuclear shape and location, and actin distribution. We found
      that 248 parameters changed significantly during fermentation. Successive use of
      principal component analysis (PCA) revealed several important features of yeast,
      providing insight into the dynamic changes in the yeast population. First, PCA
      indicated that much of the observed variability in the experiment was summarized
      in just two components: a change with a peak and a change over time. Second, PCA
      indicated the independent and important morphological features responsible for
      dynamic changes: budding ratio, nucleus position, neck position, and actin
      organization. Thus, the large amount of data provided by imaging analysis can be
      used to monitor the fermentation processes involved in beer and bioethanol
      production.

PMID- 24012107
TI  - Effect of growth rate on plasmid DNA production and metabolic performance of
      engineered Escherichia coli strains.
AB  - Two engineered Escherichia coli strains, designated VH33 and VH34, were compared
      to their parent strain W3110 in chemostat mode during plasmid DNA (pDNA)
      production. In strain VH33 the glucose uptake system was modified with the aim of
      reducing overflow metabolism. The strain VH34 has an additional deletion of the
      pyruvate kinase A gene (pykA) to increase pDNA formation. pDNA formation rates as
      well as kinetic and stoichiometric parameters were investigated in dependence of
      the growth rate within a range from 0.02 to 0.25 h(-1). Differences between
      strains were found in terms of the biomass yields on nitrogen and oxygen, as well
      as on the cell maintenance coefficients. The deletion of pykA led to a
      significantly increased pDNA yield and productivity. At an optimal growth rate of
      0.20 h(-1) it was nearly 60% higher than that of W3110 and VH33. Metabolic fluxes
      calculated by metabolite balance analysis showed differences mainly in reactions
      catalyzed by pyruvate kinase and glucose 6-phosphate dehydrogenase. The obtained
      data are useful for the design of cultivation schemes for pDNA production by E.
      coli.

PMID- 24012108
TI  - Biotransformation of bavachinin by three fungal cell cultures.
AB  - Biotransformation of bavachinin (1) was investigated using three fungal cell
      cultures of Aspergillus flavus ATCC 30899, Cunninghamella elegans CICC 40250 and
      Penicillium raistrickii ATCC 10490, respectively. Two major converted products
      were identified by LC/MS, (1)H NMR and (13)C NMR and X-ray diffraction. Two
      biocatalyst systems, A. flavus ATCC 30899 and C. elegans CICC 40250 cell
      cultures, showed a great capacity of hydroxylation and two hydroxyl groups were
      attached at C-2" and C-3" positions in the side chain of the bavachinin A-ring,
      resulting in the formation of the same compound with a name, (S)-6-((R)-2,3
      dihydroxy-3-methylbutyl)-2-(4-hydroxyphenyl)-7-methoxychromen-4-one (2). On the
      other hand, P. raistrickii ATCC 10490 cell cultures possessed the ability to
      reduction at C-4 of the substrate C-ring, resulting in the production of (2S,4R)
      2-(4-hydroxyphenyl)-7-methoxy-6-(3-methylbut-2-en-1-yl)chromen-4-ol (3).
      Furthermore, the in vitro anti-tumor activities of the above compounds were
      evaluated by MTT assay. Compared with the substrate (1), product 3 possessed
      stronger inhibition activity on the human breast cancer cell line (MCF-7) and
      slightly lower inhibition activities against Hep G2, HeLa, Hep-2 and A549 cells
      lines; while the hydroxyl product 2 possessed much lower inhibition activity on
      tumor cells lines, which might be related to the insertion of two hydroxyl
      groups. Compounds 2 and 3 were considered to be novel. It was also the first time
      to biotransform bavachinin (1) by these three fungi, which suggested the
      potential role of microbial enzymes to synthesize novel compounds from plant
      secondary metabolites. 

PMID- 24012109
TI  - Aberrant signalling by protein kinase CK2 in imatinib-resistant chronic myeloid
      leukaemia cells: biochemical evidence and therapeutic perspectives.
AB  - Chronic myeloid leukaemia (CML) is driven by the fusion protein Bcr-Abl, a
      constitutively active tyrosine kinase playing a crucial role in initiation and
      maintenance of CML phenotype. Despite the great efficacy of the Bcr-Abl-specific
      inhibitor imatinib, resistance to this drug is recognized as a major problem in
      CML treatment. We found that in LAMA84 cells, characterized by imatinib
      resistance caused by BCR-ABL1 gene amplification, the pro-survival protein kinase
      CK2 is up-regulated as compared to the sensitive cells. CK2 exhibits a higher
      protein-level and a parallel enhancement of catalytic activity. Consistently, CK2
      catalysed phosphorylation of Akt-Ser129 is increased. CK2 co-localizes with Bcr
      Abl in the cytoplasmic fraction as judged by subcellular fractionation and
      fluorescence immunolocalization. CK2 and Bcr-Abl are members of the same multi
      protein complex(es) in imatinib-resistant cells as demonstrated by co
      immunoprecipitation and co-sedimentation in glycerol gradients. Cell treatment
      with CX-4945, a CK2 inhibitor currently in clinical trials, counteracts CK2/Bcr
      Abl interaction and causes cell death by apoptosis. Interestingly, combination of
      CX-4945 with imatinib displays a synergistic effect in reducing cell viability.
      Consistently, knockdown of CK2alpha expression by siRNA restores the sensitivity
      of resistant LAMA84 cells to low imatinib concentrations. Remarkably, the CK2/Bcr
      Abl interaction and the sensitization towards imatinib obtained by CK2-inhibition
      in LAMA84 is observable also in other imatinib-resistant CML cell lines. These
      results demonstrate that CK2 contributes to strengthen the imatinib-resistance
      phenotype of CML cells conferring survival advantage against imatinib. We suggest
      that CK2 inhibition might be a promising tool for combined strategies in CML
      therapy. 

PMID- 24012110
TI  - Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular)
      germ cell cancer patients: a proof of principle.
AB  - Germ cell cancers (GCC) are the most frequent malignancy in young Caucasian
      males. GCC can consist of seminomas (SE) and non-seminomas (malignant NS:
      embryonal carcinoma (EC), yolk sac tumor (YS), choriocarcinoma (CH) and teratoma
      (TE)). Current serum-markers used for diagnosis and follow-up (AFP, hCG) are
      predominantly related to YS and CH and marker positivity can vary during disease.
      Therefore, stable markers consistently identifying more GCC components,
      specifically the stem cell components SE and EC, are of interest. Expression of
      the embryonic stem cell miR-371-3 and miR-302/367 clusters in SE/EC/YS suggest
      possible application of these micro-RNAs as GCC tumor-markers. The TSmiR protocol
      constitutes a complete, quality-controlled pipeline for the detection of miRs in
      serum, based on magnetic bead-based purification and qPCR quantification. As a
      proof of principle, TSmiR was applied to five independent serum sample series
      including 80 GCCs, 47 controls, 11 matched pre/post orchidectomy samples and 12
      no-GCC testicular masses. GCC serum samples showed a consistent, significant (p <
      0.0064) increase of miR-371/372/373/367 levels. Analogous, serum levels returned
      to baseline after orchidectomy (stage-I disease). Moreover, there was a trend
      toward higher miR levels in patients with metastasis. These results imply
      suitability for diagnosis and follow-up. TSmiR showed an overall sensitivity of
      98%, clearly outperforming the traditional serum markers AFP/hCG (36%/57%,
      sensitivity(AFP) = 3%/45%; sensitivity(hCG) = 62%/66%, SE/NS). TSmiR
      misclassified one tumor as a control. Serum AFP/hCG and TSmiR combined identified
      all T samples correctly. In conclusion, TSmiR constitutes a highly sensitive and
      reproducible serum test for GCC patients, suitable to be prospectively tested for
      diagnostic and follow-up purposes.

PMID- 24012112
TI  - Occurrence, characterization and antimicrobial susceptibility of Vibrio
      alginolyticus in the Eastern Adriatic Sea.
AB  - In 2007-2008, 162 samples (72 marine water samples, 90 swabs from the gills and
      skin) were collected from three European seabass fish farms in Eastern Adriatic.
      The aim of study was to determine the occurrence of Vibrio, to identify the
      isolated strains and to investigate their antimicrobial resistance. The
      comparison of the results obtained in spring and autumn periods indicated a
      higher Vibrio concentration in spring samplings. The greatest prevalence of
      Vibrio alginolyticus was on gills than on skin, whereas statistically significant
      differences were obtained between sampling periods with maximal prevalence in
      spring. Vibrio isolates from the marine water and from swabs of European seabass
      were analysed by DNA sequencing of partial 16S rDNA and gyrB genes and identified
      as V. alginolyticus. Isolates were highly susceptible to flumequine,
      chloramphenicol and oxytetracycline. 

PMID- 24012111
TI  - Association of biomarkers of inflammation and oxidative stress with the risk of
      chronic kidney disease in Type 2 diabetes mellitus in North Indian population.
AB  - Chronic kidney disease (CKD) is a major cause of morbidity and mortality
      worldwide. It results from diverse etiologies, diabetes being a frontrunner
      amongst them. Type 2 diabetes mellitus (DM) is being increasingly recognized as a
      proinflammatory state with increased oxidative stress which enormously increases
      the risk of micro and macro vascular diseases. This study was planned to explore
      the possible association between tumor necrosis factor-alpha (TNF-alpha), urinary
      monocyte chemoattractant protein-1 (uMCP-1), high-sensitivity C-reactive protein
      (hsCRP) and parameters of oxidative stress in patients with Type 2 diabetes
      mellitus (DM) and diabetic chronic kidney disease (DM-CKD). Fifty patients each
      were recruited in DM, DM-CKD and healthy control groups. Plasma TNF-alpha, hsCRP
      and uMCP-1 levels as inflammatory mediators were measured by ELISA, reduced
      glutathione (GSH), ferric reducing ability of plasma (FRAP) as parameters of
      antioxidant activity and malondialdehyde (MDA) as marker of oxidative stress,
      were measured spectrophotometrically. Plasma TNF-alpha, hsCRP and uMCP-1 were
      significantly higher in DM-CKD compared to DM and healthy controls. Lipid
      peroxidation, measured as MDA was significantly higher in patients with DM-CKD as
      compared to patients with DM and healthy controls. Further, antioxidant capacity
      of blood measured as FRAP and GSH was found to be significantly lower in patients
      with DM and DM-CKD as compared to healthy controls (p<0.001). Plasma TNF-alpha
      and uMCP-1 showed a significant positive correlation with HbA1c (r=0.441, 0.643),
      hsCRP (r=0.400, 0.584) and MDA (r=0.423, 0.759) and significant negative
      correlation with GSH (R=-0.370, -0.800) and FRAP (r=-0.344, -0.684) Increased
      inflammatory markers viz. TNF-alpha, hsCRP and uMCP-1 and markers of oxidative
      stress i.e. increased MDA and decreased GSH and FRAP in DM-CKD suggest an
      important role of inflammation and oxidative stress in the pathogenesis of renal
      damage in diabetic patients. 

PMID- 24012113
TI  - Contaminants in magnificent frigatebird eggs from Barbuda, West Indies.
AB  - We examined persistent organic pollutant and trace element concentrations in eggs
      of magnificent frigatebirds (Fregata magnificens), a species of conservation
      concern breeding in the West Indies. Despite that frigatebirds feed at high
      positions in tropical marine food chains, we detected low levels of most
      contaminants, suggesting limited contamination of their prey. 

PMID- 24012114
TI  - Quantitative high-speed laryngoscopic analysis of vocal fold vibration in
      fatigued voice of young karaoke singers.
AB  - PURPOSE: The present study aimed to determine whether there were physiological
      differences in the vocal fold vibration between nonfatigued and fatigued voices
      using high-speed laryngoscopic imaging and quantitative analysis. METHODS: Twenty
      participants aged from 18 to 23 years (mean, 21.2 years; standard deviation, 1.3
      years) with normal voice were recruited to participate in an extended singing
      task. Vocal fatigue was induced using a singing task. High-speed laryngoscopic
      image recordings of /i/ phonation were taken before and after the singing task.
      The laryngoscopic images were semiautomatically analyzed with the quantitative
      high-speed video processing program to extract indices related to the
      anteroposterior dimension (length), transverse dimension (width), and the speed
      of opening and closing. RESULTS: Significant reduction in the glottal length-to
      width ratio index was found after vocal fatigue. Physiologically, this indicated
      either a significantly shorter (anteroposteriorly) or a wider (transversely)
      glottis after vocal fatigue. CONCLUSION: The high-speed imaging technique using
      quantitative analysis has the potential for early identification of vocally
      fatigued voice.

PMID- 24012115
TI  - Effects of voice therapy in school-age children.
AB  - OBJECTIVES: To assess the overall efficacy of voice therapy for dysphonia in
      school-age children in two different cities in Turkey. STUDY DESIGN:
      Retrospective cohort study. METHODS: Ninety-nine outpatients aged 7-15 years with
      persistent hoarseness for at least 2 months as a primary symptom. Ratings of the
      Grade, Roughness, Breathiness, Asthenia, and Strain (GRBAS) scale, s/z ratio, and
      maximum phonation time (MPT). Voice therapy outcome data collected on three types
      of voice therapy (physiological, hygienic, and symptomatic). SETTING: Outpatient
      clinics in university hospitals in two different cities in Turkey. RESULTS: Voice
      therapy improved voice quality as assessed by an observer according to GRBAS
      rating system (P<0.0001). All the subjects demonstrated varying degrees of
      hoarseness (G1-G3) and strained (S1-S3) voices. Varying degrees of roughness (R1
      R3) and breathiness (B1-B3) were also noted. In general, changes to the value of
      the grade (the measure of the overall degree of voice deviance) were
      statistically significant (t = -8.3; P<0.0001) before and after therapy.
      Significant changes were found in the s/z ratio when the values were compared
      before and after therapy sessions (t=11.08; P<0.0001). Changes in MPT were
      statistically significant for all types of voice therapy (P<0.0001). CONCLUSIONS:
      Vocal nodules were the main cause of the school-age children's voice problems,
      accounting for 62.6% of the cases. Different types of voice therapy techniques
      could be used in school-age children. Many of these techniques can successfully
      restore the normal voice. However, in this study, all subjective voice ratings
      such as GRBAS, s/z ratio, and MPT statistically changed by symptomatic voice
      therapy techniques. Symptomatic voice therapy was found to be a successful method
      of therapy.

PMID- 24012116
TI  - Intracardiac juvenile xanthogranuloma with presentation in adulthood.
AB  - Juvenile xanthogranuloma is the most frequent type of non-Langerhans cell
      histiocytosis. It most commonly presents in infancy and early childhood;
      manifesting as cutaneous lesions on the head, neck, and trunk that suddenly
      appear and usually undergo spontaneous regression. Extracutaneous involvement,
      although rare, may occur along with the cutaneous form or in isolation. It most
      frequently involves the eye, deep subcutaneous tissues, lung, and liver.
      Involvement of the heart is exceptionally rare, with only seven reports found in
      the English literature, all affecting infants. We present the first report of an
      intracardiac juvenile xanthogranuloma in an adult. 

PMID- 24012117
TI  - Can statins prevent pregnancy complications?
AB  - Statins are potent inhibitors of cholesterol biosynthesis. The beneficial effects
      of the statins in preventing cardiovascular diseases are not entirely due to
      cholesterol reduction. Numerous studies suggest that the benefits observed with
      statins may be mediated by pleiotropic effects that are cholesterol-independent.
      There is now compelling evidence that statin therapy may diminish inflammation
      and oxidative stress, increase angiogenesis, inhibit the coagulation cascade and
      protect the endothelium. Several animal studies demonstrated that statins prevent
      pregnancy complications such as recurrent miscarriages and preeclampsia.
      Epidemiological data collected to date suggest that statins are not major
      teratogens. Clinical trials should be performed to demonstrate the effectiveness
      of statins in preventing bad pregnancy outcomes in women. Some of these trials
      recently started. This article summarizes the numerous effects of statins that
      can contribute to the pregnancy protection observed in animal models. 

PMID- 24012118
TI  - Synthesis and binding affinity of new 1,4-disubstituted triazoles as potential
      dopamine D(3) receptor ligands.
AB  - A series of new 1,4-disubstituted triazoles was prepared from appropriate
      arylacetylenes and aminoalkylazides using click chemistry methodology. These
      compounds were evaluated as potential ligands on several subtypes of dopamine
      receptors in in vitro competition assays, showing high affinity for dopamine D3
      receptors, lower affinity for D2 and D4, and no affinity for the D1 receptors.
      Compound 18 displayed the highest affinity at the D3 receptor with a Ki value of
      2.7 nM, selectivity over D2 (70-fold) and D4 (200-fold), and behaviour as a
      competitive antagonist in the low nanomolar range.

PMID- 24012119
TI  - Gardovatine, a novel Strychnos-Strychnos bisindole alkaloid with cytotoxicity
      from Gardneria oveta.
AB  - Gardovatine (1), the first Strychnos-Strychnos alkaloid with a C3/C7 cleaved
      backbone, was isolated from twigs and leaves of Gardneria ovate, together with an
      analogue divarine (2). The structure was established by extensive spectroscopic
      methods. Both compounds showed potential cytotoxicities against five human cancer
      cell lines. 

PMID- 24012120
TI  - Discovery and synthesis of novel benzofurazan derivatives as inhibitors of
      influenza A virus.
AB  - The identification of a novel hit compound inhibitor of the protein-protein
      interaction between the influenza RNA-polymerase PA and PB1 subunits has been
      accomplished by means of high-throughput screening. A small family of
      structurally related molecules has been synthesized and biologically evaluated
      with most of the compounds showing micromolar potency of inhibition against viral
      replication. 

PMID- 24012121
TI  - Synthesis and SAR studies of 5-(pyridin-4-yl)-1,3,4-thiadiazol-2-amine
      derivatives as potent inhibitors of Bloom helicase.
AB  - Human cells utilize a variety of complex DNA repair mechanisms in order to combat
      constant mutagenic and cytotoxic threats from both exogenous and endogenous
      sources. The RecQ family of DNA helicases, which includes Bloom helicase (BLM),
      plays an important function in DNA repair by unwinding complementary strands of
      duplex DNA as well as atypical DNA structures such as Holliday junctions.
      Mutations of the BLM gene can result in Bloom syndrome, an autosomal recessive
      disorder associated with cancer predisposition. BLM-deficient cells exhibit
      increased sensitivity to DNA damaging agents indicating that a selective BLM
      inhibitor could be useful in potentiating the anticancer activity of these
      agents. In this work, we describe the medicinal chemistry optimization of the hit
      molecule following a quantitative high-throughput screen of >355,000 compounds.
      These efforts lead to the identification of ML216 and related analogs, which
      possess potent BLM inhibition and exhibit selectivity over related helicases.
      Moreover, these compounds demonstrated cellular activity by inducing sister
      chromatid exchanges, a hallmark of Bloom syndrome. 

PMID- 24012122
TI  - Recognition of HIV-TAR RNA using neomycin-benzimidazole conjugates.
AB  - Synthesis of a novel class of compounds and their biophysical studies with TAR
      RNA are presented. The synthesis of these compounds was achieved by conjugating
      neomycin, an aminoglycoside, with benzimidazoles modeled from a B-DNA minor
      groove binder, Hoechst 33258. The neomycin-benzimidazole conjugates have varying
      linkers that connect the benzimidazole and neomycin units. The linkers of varying
      length (5-23 atoms) in these conjugates contain one to three triazole units. The
      UV thermal denaturation experiments showed that the conjugates resulted in
      greater stabilization of the TAR-RNA than either neomycin or benzimidazole used
      in the synthesis of conjugates. These results were corroborated by the FID
      displacement and tat-TAR inhibition assays. The binding of ligands to the TAR-RNA
      is affected by the length and composition of the linker. Our results show that
      increasing the number of triazole groups and the linker length in these compounds
      have diminishing effect on the binding to TAR-RNA. Compounds that have shorter
      linker length and fewer triazole units in the linker displayed increased affinity
      towards the TAR RNA. 

PMID- 24012123
TI  - New chemotypes for wALADin1-like inhibitors of delta-aminolevulinic acid
      dehydratase from Wolbachia endobacteria.
AB  - Substituted benzimidazoles of the wALADin1-family have recently been identified
      as a new class of species-selective inhibitors of delta-aminolevulinic acid
      dehydratase (ALAD) from Wolbachia endobacteria of parasitic filarial worms. Due
      to its Wolbachia-dependent antifilarial activity, wALADin1 is a starting point
      for the development of new drugs against filarial nematodes. We now present
      several other chemotypes of ALAD inhibitors that have been identified based upon
      their molecular similarity to wALADin1. A tricyclic quinoline derivative
      (wALADin2) with a different inhibitory mechanism and improved inhibitory potency
      and selectivity may represent an improved drug lead candidate. 

PMID- 24012125
TI  - Chronic fatigue: a tiring clinical challenge.

PMID- 24012124
TI  - CK2 inhibitor CX4945 induces sequential inactivation of proteins in the signaling
      pathways related with cell migration and suppresses metastasis of A549 human lung
      cancer cells.
AB  - Casein kinase 2 (CK2) is known to be involved in various cellular processes such
      as cell cycle, apoptosis and proliferation. It has been reported that the
      inhibition of CK2 induced by recently developed small molecule CX4945 shows anti
      cancer effects including anti-proliferation and anti-angiogenesis in several
      different cancers including prostate cancer. Here we report that migration and
      invasion of A549 human lung cancer cells are suppressed by the inhibition of CK2
      induced by CX4945. We found that CX4945 sequentially attenuates the proteins in
      PI3K/Akt and MAPK pathways, two signaling pathways related with cell migration.
      This sequential control of signal pathways inhibits the expression of membrane
      type 1-matrix metalloproteinase and this leads to the selective attenuation of
      one of the gelatinases, MMP-2, which can degrade components of extracellular
      matrix, and metastasis of A549 human lung cancer cell. 

PMID- 24012126
TI  - Frequency of vaginal candida colonization and relationship between metabolic
      parameters in children with type 1 diabetes mellitus.
AB  - OBJECTIVES: Patients with diabetes mellitus (DM) are at risk for vulvovaginal
      candidasis. The aim of this study was to determine the species-specific
      prevalence rate and risk of candidiasis in patients with type 1 DM. METHODS:
      Children aged between 8-16 years were included in the study. Clinical and
      laboratory features of diabetes and evidence of genital symptoms were recorded.
      Vaginal swabs were taken from patients and placed on Sabouraud's dextrose agar
      and incubated. Following fasting overnight for 12 hours venous blood samples were
      taken simultaneously for analyses of blood glucose, HbA1c, and lipid profile. A
      simple 1-time fluconazole treatment regimen was used to treat patients with vulvo
      vaginal candidiasis. RESULTS: Candida species were isolated in 30 of 76 (39%)
      swabs of patients with type 1 DM. Subjects who had candida colonization and
      candidiasis were all acute. The predominant candida species isolated from
      patients with type 1 DM were C.albicans 50%, C. glabrata 36.6%, C.crusei 3.3%,
      C.spesies 6.6%, and C.dubliniensis 3.3%. 42 patients had symptoms.The prevalence
      of candidiasis in symptomatic patients was 59.2%. Subjects with vulvo-vaginal
      candidiasis had higher mean HbA1c when compared to those who had no such
      infection (P = .047). CONCLUSIONS: There seems to be a significant link between
      hyperglycemia and vulvo-vaginal candidiasis in patients with type 1 DM. Improving
      glucose control may reduce the risk of candidiasis and potentially symptomatic
      infection among children with diabetes. Because of high rate of colonization with
      candida species in diabetes, patients should undergo periodic screening for
      genital candidiasis.

PMID- 24012127
TI  - The prescribing of contraceptives for adolescents in German gynecologic practices
      in 2007 and 2011: a retrospective database analysis.
AB  - OBJECTIVE: To investigate the prescribing trend of contraceptives in adolescent
      girls aged 12-18 years and to compare prescribing patterns of the most frequently
      used contraceptives among this population in Germany in 2007 and 2011. METHODS: A
      retrospective cohort study was conducted to analyze contraceptive prescriptions
      written by gynecologists in 2007 and 2011 in Germany by using the IMS Disease
      Analyzer database (IMS HEALTH). All adolescent girls aged 12-18 years with at
      least 1 prescription of a contraceptive drug in 2007 or 2011 were identified. The
      prevalence of contraceptive prescriptions was calculated and the types of
      contraceptive substances prescribed were examined. RESULTS: A total of 21,026
      teenage girls in 2007 and 18,969 in 2011 received contraceptive prescriptions.
      The prevalence of contraceptive prescribing rose significantly between 2007 and
      2011 (P < .001). The percentage of teen girls who received prescriptions of
      levonorgestrel and chlormadinone pills was significantly higher in 2011 compared
      to 2007 (P < .001). However, the portion of contraceptive pills containing
      drospirenone or desogestrel significantly decreased in 2011 compared to 2007 (P <
      .01). CONCLUSION: There was a significant increase in contraceptive prescription
      usage among adolescent girls between 2007 and 2011 in Germany. However, the
      prescription behavior of doctors also changed; they consequently prescribed
      contraceptives with more evidence. Further research is needed to better
      understand the various factors associated with contraceptive use among this
      population.

PMID- 24012128
TI  - Vulvo-vaginitis in prepubertal girls: new ways of administering old drugs.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness and safety of local vs systemic
      antibiotic treatment in the management of recurrent vulvovaginitis in children.
      DESIGN: Randomized treatment and follow-up of 90 cases of persistent
      vulvovaginitis. SETTING: The Department of Medicine and Health Sciences,
      Institute of Gynecology and Obstetrics, University of Molise, Italy. METHODS:
      Between January 2009 and December 2012, 90 prepubertal girls (Tanner Stage I)
      aged 6-12 years, with recurrent discharge not responding to common hygienic
      measures and not suspected of being sexually abused, were treated, 45 patients
      with oral antibiotic treatment (group 1) and 45 patients with a local antibiotic
      treatment (group 2). Vaginal cultures were prepared before treatment and follow
      ups were made after 3 months. RESULTS: Bacterial pathogens were isolated in
      vaginal secretions of 84/90 (93%) girls. There were 6 girls receiving antibiotic
      treatment who had persistent discharge and repetitive isolations of Escherichia
      coli. Administration type was selected at random. Symptoms and signs were
      resolved in all girls, but we observed 1 recurrence (2.22%) in group 2 vs 6
      recurrences (13.33%) in group 1 (P = .049). In group 1 we observed 3 cases
      (6.67%) of gastro-intestinal side effects vs no cases in group 2 (P = .079).
      CONCLUSION: Topical medication based on netilmicin, associated with Benzalkonium
      Chloride, showed a clinical and microbiological effectiveness in first-line
      treatment of bacterial vulvovaginitis in children, comparable to conventional
      drugs; so local treatment may be a good alternative to systemic treatment
      decreasing the use of oral antibiotics in young people and related risks of
      bacterial resistances.

PMID- 24012129
TI  - Practices and perceptions among pediatricians regarding adolescent contraception
      with emphasis on intrauterine contraception.
AB  - STUDY OBJECTIVE: This study was conducted to characterize pediatricians' current
      practice patterns and perceived barriers related to adolescent contraception
      counseling with an emphasis on intrauterine contraception (IUC). DESIGN: We
      performed a mailed survey study to 400 general pediatricians. SETTING: Surveys
      were mailed to pediatricians at their individual office locations. PARTICIPANTS:
      General pediatricians belonging to the Massachusetts Pediatric Society were
      included in the study. INTERVENTIONS: The survey instrument assessed current
      practice patterns and perspectives as related to contraception counseling for
      adolescents. MAIN OUTCOME MEASURES: Use of contraception among adolescent
      patients, policy to recommend IUC to adolescents in various clinical scenarios,
      and barriers to adolescent contraceptive counseling. RESULTS: Over 50% of
      pediatricians considered abstinence their favored method of contraception for
      adolescents, while fewer than 20% reported discussing IUC as an option. Female
      pediatricians were more likely to discuss IUC (25% vs 8%, P = .01), as were
      younger pediatricians (28% vs 14%, P = .13). Given 8 clinical scenarios suitable
      for IUC use, less than 25% of pediatricians would offer IUC to a teen unless she
      had a history of a vaginal delivery or abortion. Seventy percent of pediatricians
      reported lack of training with IUC, and more than 30% reported legal, fertility
      and parental concerns as barriers to discussing IUC with adolescents.
      CONCLUSIONS: Efforts are warranted to improve the education of pediatricians
      regarding the most current guidelines for proper IUC use in adolescents with the
      goal to increase the frequency with which this effective contraceptive method is
      discussed with this vulnerable population.

PMID- 24012130
TI  - Prevalence of hemostatic disorders in adolescents with abnormal uterine bleeding.
AB  - STUDY OBJECTIVE: To evaluate the incidence of hemostatic disorders in a
      population of adolescents with various patterns of abnormal uterine bleeding
      (AUB). DESIGN: Retrospective observational study. SETTING: University hospital.
      PARTICIPANTS: One hundred thirteen adolescents with AUB; mean age at menarche and
      mean age at the onset of symptoms 12 +/- 1.2 years and 13.5 +/- 2.8 years,
      respectively. MAIN OUTCOME MEASURES: Data on menstrual history, bleeding
      symptoms, co-existing medical conditions, and medical therapies were assessed.
      All patients were screened for hemostatic disorders with laboratory testing. The
      incidence of the disorders was calculated. Subjects were further divided in 2
      groups based on whether the AUB started in the first 2 years from menarche (group
      1) or later (group 2). A statistical analysis was performed using a chi-square
      test to compare incidence of hemostatic disorders between the groups. RESULTS:
      One hundred thirteen adolescents with AUB were identified. Overall, 54 (47.8%)
      patients had some underlying hemostatic disorder, of which a platelet dysfunction
      was the most common (17.7%). Von Willebrand disease was detected in 13.3% of
      cases and a deficiency of a coagulation factor in 12.4%. In 7.1% of patients an
      isolated increase of bleeding time was observed. When divided in 2 groups, 44.2%
      of patients in group 1 and 59.2% in group 2 had a coagulation disorders, with no
      statistically significant difference between the 2 groups (P = .17). CONCLUSION:
      AUB in adolescents is frequently associated with an underlying disorder of
      hemostasis, most commonly a platelet function disorder. The results highlight the
      importance of screening for coagulation disorders in adolescents with AUB,
      independently from the gynecologic age at onset.

PMID- 24012131
TI  - Lifestyle intervention in general practice for physical activity, smoking,
      alcohol consumption and diet in elderly: a randomized controlled trial.
AB  - The purpose of the study was to compare the effectiveness of programmed and
      intensified intervention on lifestyle changes, including physical activity,
      cigarette smoking, alcohol consumption and diet, in patients aged >= 65 with the
      usual care of general practitioners (GP). In this multicenter randomized
      controlled trial, 738 patients aged >= 65 were randomly assigned to receive
      intensified intervention (N = 371) or usual care (N = 367) of a GP for lifestyle
      changes, with 18-month follow-up. The main outcome measures were physical
      activity, smoking, alcohol consumption and diet. The study was conducted in 59
      general practices in Croatia between May 2008 and May 2010. The patients' mean
      age was 72.3 +/- 5.2 years. Significant diet correction was achieved after 18
      month follow-up in the intervention group, comparing to controls. More patients
      followed strictly Mediterranean diet and consumed healthy foods more frequently.
      There was no significant difference between the groups in physical activity,
      tobacco smoking and alcohol consumption or diet after the intervention. In
      conclusion, an 18-month intensified GP's intervention had limited effect on
      lifestyle habits. GP intervention managed to change dietary habits in elderly
      population, which is encouraging since elderly population is very resistant
      regarding lifestyle habit changes. Clinical trial registration number.
      ISRCTN31857696.

PMID- 24012134
TI  - Life cycle assessment of mobility options using wood based fuels--comparison of
      selected environmental effects and costs.
AB  - An environmental assessment and a cost analysis were conducted for mobility
      options using electricity, hydrogen, ethanol, Fischer-Tropsch diesel and methane
      derived from wood. Therefore, the overall life cycle with regard to greenhouse
      gas emissions, acidifying emissions and fossil energy demand as well as costs is
      analysed. The investigation is carried out for mobility options in 2010 and gives
      an outlook to the year 2030. Results show that methane utilization in the car is
      beneficial with regard to environmental impacts (e.g. 58.5 g CO2-eq./km) and
      costs (23.1 ?-ct./km) in 2010, especially in comparison to hydrogen usage (132.4
      g CO2-eq./km and 63.9 ?-ct./km). The electric vehicle construction has high
      environmental impacts and costs compared to conventional vehicles today, but with
      technical improvements and further market penetration, battery electric vehicles
      can reach the level of concepts with combustion engines in future applications
      (e.g. cost decrease from 38.7 to 23.4 ?-ct./km).

PMID- 24012135
TI  - Genetic diversity of Chlamydia pecorum strains in wild koala locations across
      Australia and the implications for a recombinant C. pecorum major outer membrane
      protein based vaccine.
AB  - The long term survival of the koala (Phascolarctos cinereus) is at risk due to a
      range of threatening processes. A major contributing factor is disease caused by
      infection with Chlamydia pecorum, which has been detected in most mainland koala
      populations and is associated with ocular and genital tract infections. A
      critical aspect for the development of vaccines against koala chlamydial
      infections is a thorough understanding of the prevalence and strain diversity of
      C. pecorum infections across wild populations. In this study, we describe the
      largest survey (403 koalas from eight wild populations and three wildlife
      hospitals) examining the diversity of C. pecorum infections. 181 of the 403
      koalas tested (45%) positive for C. pecorum by species-specific quantitative PCR
      with infection rates ranging from 20% to 61% in the eight wild populations
      sampled. The ompA gene, which encodes the chlamydial major outer membrane protein
      (MOMP), has been the major target of several chlamydial vaccines. Based on our
      analysis of the diversity of MOMP amino types in the infected koalas, we conclude
      that, (a) there exists significant diversity of C. pecorum strains in koalas,
      with 10 distinct, full length C. pecorum MOMP amino types identified in the 11
      koala locations sampled, (b) despite this diversity, there are predicted T and B
      cell epitopes in both conserved as well as variable domains of MOMP which suggest
      cross-amino type immune responses, and (c) a recombinant MOMP-based vaccine
      consisting of MOMP "F" could potentially induce heterotypic protection against a
      range of C. pecorum strains. 

PMID- 24012136
TI  - Assessing the mechanism of response in the retrosplenial cortex of good and poor
      navigators.
AB  - The retrosplenial cortex (RSC) is consistently engaged by a range of tasks that
      examine episodic memory, imagining the future, spatial navigation, and scene
      processing. Despite this, an account of its exact contribution to these cognitive
      functions remains elusive. Here, using functional MRI (fMRI) and multi-voxel
      pattern analysis (MVPA) we found that the RSC coded for the specific number of
      permanent outdoor items that were in view, that is, items which are fixed and
      never change their location. Moreover, this effect was selective, and was not
      apparent for other item features such as size and visual salience. This detailed
      detection of the number of permanent items in view was echoed in the
      parahippocampal cortex (PHC), although the two brain structures diverged when
      participants were divided into good and poor navigators. There was no difference
      in the responsivity of the PHC between the two groups, while significantly better
      decoding of the number of permanent items in view was possible from patterns of
      activity in the RSC of good compared to poor navigators. Within good navigators,
      the RSC also facilitated significantly better prediction of item permanence than
      the PHC. Overall, these findings suggest that the RSC in particular is concerned
      with coding the presence of every permanent item that is in view. This mechanism
      may represent a key building block for spatial and scene representations that are
      central to episodic memories and imagining the future, and could also be a
      prerequisite for successful navigation. 

PMID- 24012137
TI  - Mechanism of disorientation: reality filtering versus content monitoring.
AB  - Disorientation is frequent after brain damage. It is a constituent component of
      post-traumatic amnesia and was part of the original definition of the Korsakoff
      syndrome, together with amnesia and confabulations. Orbitofrontal reality
      filtering is a pre-conscious memory control process that has been held
      accountable for disorientation and a specific type of confabulations that
      patients act upon. A recent study questioned the specificity of this process and
      suggested that confabulating patients who failed in orbitofrontal reality
      filtering similarly failed to monitor the precise content of memories, a critical
      step within the strategic retrieval account, which describes a series of
      processes leading up to the recollection of memories. In the present study we
      combined the proposed experimental requirements of both processes in a single
      continuous recognition task and tested a group of 21 patients with a matched
      deficit of delayed free recall. We found that only deficient reality filtering,
      but not content monitoring, significantly correlated with disorientation and
      distinguished between confabulators and non-confabulators. Thus, reality
      confusion, as evident in disorientation and behaviourally spontaneous
      confabulation, primarily reflects an inability to monitor memories' relation with
      ongoing reality rather than to monitor their precise content. 

PMID- 24012138
TI  - Heavy metal distribution in an urban wetland impacted by combined sewer overflow.
AB  - The heavy metal content and distribution in an urban wetland affected by combined
      sewer overflow (CSO) discharge during dry conditions was evaluated. Metals
      identified in the CSO discharge were also measured upstream and downstream of the
      CSO. Metals were detected in the acid-extractable fraction of the wetland
      sediments and the roots of Phragmites australis plants. Sediment from the banks
      of a pool created by the CSO, and from a clay bed upstream were found to be
      moderately contaminated with Cu, Pb and Zn. Micro X-ray fluorescence (MU-XRF) of
      Phragmites roots from the CSO banks showed a correlation in the spatial
      distribution of Fe and Mn, attributed to the formation of mineral plaques on the
      root surface. Micro X-ray absorption near edge spectroscopy (MU-XANES) revealed
      that Cu and Zn were complexed with the organic ligands phytate and cysteine. The
      findings indicated that continuous discharge from the CSO is a source of heavy
      metals to the wetland. Metals bound to sediments are susceptible to
      remobilization and subsequent transport, whereas those associated with Phragmites
      roots may be more effectively sequestered. These observations provide insight
      into the behavior of heavy metals in urban areas where CSOs discharge into
      wetlands. 

PMID- 24012139
TI  - Cyanobacterial toxins: modes of actions, fate in aquatic and soil ecosystems,
      phytotoxicity and bioaccumulation in agricultural crops.
AB  - The occurrence of harmful cyanobacterial blooms in surface waters is often
      accompanied by the production of a variety of cyanotoxins. These toxins are
      designed to target in humans and animals specific organs on which they act:
      hepatotoxins (liver), neurotoxins (nervous system), cytotoxic alkaloids, and
      dermatotoxins (skin), but they often have important side effects too. When
      introduced into the soil ecosystem by spray irrigation of crops they may affect
      the same molecular pathways in plants having identical or similar target organs,
      tissues, cells or biomolecules. There are also several indications that
      terrestrial plants, including food crop plants, can bioaccumulate cyanotoxins and
      present, therefore, potential health hazards for human and animals. The number of
      publications concerned with phytotoxic effects of cyanotoxins on agricultural
      plants has increased recently. In this review, we first examine different
      cyanotoxins and their modes of actions in humans and mammals and occurrence of
      target biomolecules in vegetable organisms. Then we present environmental
      concentrations of cyanotoxins in freshwaters and their fate in aquatic and soil
      ecosystems. Finally, we highlight bioaccumulation of cyanotoxins in plants used
      for feed and food and its consequences on animals and human health. Overall, our
      review shows that the information on the effects of cyanotoxins on non-target
      organisms in the terrestrial environment is particularly scarce, and that there
      are still serious gaps in the knowledge about the fate in the soil ecosystems and
      phytotoxicity of these toxins. 

PMID- 24012140
TI  - Exposure estimates to Fusarium mycotoxins through cereals intake.
AB  - Mycotoxins are harmful substances produced by fungi in several commodities with a
      widespread presence in foodstuffs. Human exposure to mycotoxins occurs mainly by
      contaminated food. The quantitation of mycotoxins in cereal-based food, highly
      consumed by different age population, is of concern. In this survey, 159 cereal
      based samples classified as wheat, maize and rice-based, have been evaluated for
      the occurrence of patulin, deoxynivalenol, 3-acetyl-deoxynivalenol, fusarenon-X,
      diacetoxyscirpenol, nivalenol, neosolaniol, HT-2, T-2 and zearalenone by gas
      chromatography-tandem mass spectrometry. Intakes were calculated for average
      consumers among adults, children and infants and compared with the tolerable
      daily intakes (TDI). Data obtained were used to estimate the potential exposure
      levels. 65.4% of the samples were contaminated with at least one mycotoxin and
      15.7% of the analyzed samples showed co-occurrence of mycotoxin. The dietary
      exposure to HT-2 and T-2 toxins was estimated as 0.010 and 0.086 MUg kg(-1) bw d(
      1), amounting to 10% and 86% of the TDI, for adults and infants respectively.
      These results back up the necessity to take a vigilant attitude in order to
      minimize human intake of mycotoxins.

PMID- 24012141
TI  - Quantification of the interactions between Ca2+, Hg2+ and extracellular polymeric
      substances (EPS) of sludge.
AB  - The interactions between metals (Ca(2+) and Hg(2+)) and extracellular polymeric
      substances (EPS) extracted from the aerobic and anaerobic sludge in wastewater
      treatment reactors were investigated using a combination of zeta potential
      measurement and 3-dimensional excitation-emission matrix (EEM) fluorescence
      spectroscopy with parallel factor (PARAFAC) analysis. Results show that Ca(2+)
      had no substantial effects on the EEM fluorescence spectra of the EPS, but their
      zeta potentials increased with the increasing Ca(2+) dosage. However, Hg(2+) had
      a significant effect on the EEM fluorescence spectra of the EPS, while their zeta
      potentials seemed not to be affected by the dose of Hg(2+). The interactions
      between Hg(2+) and EPS were elucidated using the fluorescence quenching with
      PARAFAC analysis, while the interactions between Ca(2+) and EPS were evaluated by
      the zeta potential technique. The binding constants for Hg(2+) and EPS were two
      orders of magnitude higher than those for Ca(2+) and EPS, suggesting that the
      binding mechanisms between Ca(2+) and EPS were different from those between
      Hg(2+) and EPS. The results might be useful for understanding the roles of EPS in
      bacterial self-protection against heavy metals and the aggregate formation
      mechanisms through ionic bridging interactions. 

PMID- 24012142
TI  - Aqueous solubility (in the range between 298.15 and 338.15 K), vapor pressures
      (in the range between 10(-5) and 80 Pa) and Henry's law constant of 1,2,3,4
      dibenzanthracene and 1,2,5,6-dibenzanthracene.
AB  - Aqueous solubility and vapor pressures of 1,2,3,4-dibenzanthracene and 1,2,5,6
      dibenzanthracene were determined using dynamic saturation methods. For the two
      isomers, aqueous solubility is in the range between 10(-10) and 10(-2) in molar
      fraction corresponding to temperature between 298.15 and 338.15K. Vapor pressures
      of the pure solutes range from 10(-5) to 80 Pa. Prior to the study of the two
      dibenzanthracenes and in order to check the experimental procedures, solubility
      of fluoranthene (between 298 and 338 K) and vapor pressures of phenanthrene and
      fluoranthene (between 300 and 470 K) were measured. From aqueous solubility data
      coupled with the vapor pressures of the pure solutes, partition coefficient air
      water, KAW, and Henry's constant, KH, of environmental relevance were calculated.

PMID- 24012143
TI  - Investigating affective prosody in psychosis: a study using the Comprehensive
      Affective Testing System.
AB  - Affective prosody is substantially impaired in schizophrenia, yet little is known
      about affective prosody in bipolar disorder (BD). The aim of this study was to
      examine affective prosody performance in schizophrenia, schizoaffective disorder
      and BD on a newly released standardised assessment to further our understanding
      of BD performance. Fifty-four schizophrenia, 11 schizoaffective and 43 BD
      patients were compared with 112 healthy controls (HC) on four affective prosody
      subtests of the Comprehensive Affective Testing System (CATS). Schizophrenia
      patients showed a 10% reduction in accuracy on two subtests compared to HC. BD
      showed a trend for performance intermediary to schizophrenia and HC; and
      schizoaffective patients performed more like HC on these four affective prosody
      measures. Severity of current auditory hallucination, across all patients, was
      related to task performance on three of the measures. These data confirm that
      schizophrenia and BD have reduced affective prosody performance, with deficits in
      BD being less pronounced than schizophrenia. The schizoaffective results in this
      study should be interpreted with caution due to small sample size. 

PMID- 24012144
TI  - Generating protective immunity against genital herpes.
AB  - Genital herpes is an incurable, chronic disease that affects millions of people
      worldwide. Not only does genital herpes cause painful, recurrent symptoms, it is
      also a significant risk factor for the acquisition of other sexually transmitted
      infections such as HIV-1. Antiviral drugs are used to treat herpes simplex virus
      (HSV) infection, but they cannot stop viral shedding and transmission. Thus,
      developing a vaccine that can prevent or clear infection will be crucial in
      limiting the spread of disease. In this review we outline recent studies that
      improve our understanding of host responses against HSV infection, discuss past
      clinical vaccine trials, and highlight new strategies for vaccine design against
      genital herpes. 

PMID- 24012145
TI  - Models of visual word recognition.
AB  - Reading is a complex process that draws on a remarkable number of diverse
      perceptual and cognitive processes. In this review, I provide an overview of
      computational models of reading, focussing on models of visual word recognition
      how we recognise individual words. Early computational models had 'toy' lexicons,
      could simulate only a narrow range of phenomena, and frequently had fundamental
      limitations, such as being able to handle only four-letter words. The most recent
      models can use realistic lexicons, can simulate data from a range of tasks, and
      can process words of different lengths. These models are the driving force behind
      much of the empirical work on reading. I discuss how the data have guided model
      development and, importantly, I also provide guidelines to help interpret and
      evaluate the contribution the models make to our understanding of how we read. 

PMID- 24012146
TI  - Use of selenium-silymarin mix reduces lower urinary tract symptoms and prostate
      specific antigen in men.
AB  - The aim of this double-blind, placebo controlled clinical trial was to assess the
      effects of a combination of selenium and silymarin in men with lower urinary
      tract symptoms, benign prostatic hyperplasia and a prostate specific antigen
      (PSA) <=2.5ng/ml. The volunteers were randomized to two groups: the first one
      (n=26) received 240MUg selenium (in the form of yeast l-selenomethionine) plus
      570mg silymarin daily for 6 months and the second (n=29) received placebo.
      Outcome measures were changes in the International Prostate Symptom Score (IPSS),
      bladder volume (V), urinary flow rate, ultrasound estimated postvoid residual
      urine volume (RV), serum PSA, testosterone and selenium levels, safety clinical
      biochemistry, hematology and oxidative stress parameters at baseline and on day
      180. The results showed statistically significant differences (p<0.05) between
      treatment and control groups for the following parameters: IPSS score, urodynamic
      parameters: maximal rate of urine flow (Qmax), average flow (Qave), V and RV,
      total PSA value and serum selenium levels. There was a significant reduction in
      PSA in the selenium-silymarin group but no effect on blood testosterone level.
      Overall the treatment was well-tolerated with no adverse effects. 

PMID- 24012147
TI  - Skin dimpling as a complication of amniocentesis: histopathologic findings.

PMID- 24012148
TI  - Incidental radiation to axilla in early breast cancer treated with intensity
      modulated tangents and comparison with conventional and 3D conformal tangents.
AB  - PURPOSE: To analyze incidental radiation doses to minimally dissected axilla with
      Intensity modulated radiotherapy (IMRT), 3D conformal radiotherapy (3DCRT) and
      standard tangents (ST). METHODS & MATERIALS: We prospectively evaluated
      incidental radiation to axilla in fifty cases of early breast cancer treated with
      breast conservation surgery with sentinel node biopsy alone followed by whole
      breast irradiation with IMRT. Three plans were devised for each CT dataset,
      comprising ST, 3DCRT and IMRT tangents. Doses to axillary nodal levels I, II and
      III were evaluated for mean dose, V95, V90, V80 and V50. Comparisons were made
      using ANOVA. RESULTS: The mean doses delivered to axilla by the three techniques
      (IMRT, 3DCRT, ST) were: 78% (range 67-90, SD +/- 5.2%), 80% (63-95, +/-7.5%) and
      87% (73-98, +/-4.8%) for level I (IMRT vs ST; p = 0.037); 70% (46-89, +/-12.4%),
      72% (34-93, +/-15.5%) and 65% (29-87, +/-11.8%) for level II; and 51% (28-76, +/
      11.1%), 53% (19-86, +/-13.7%) and 41% (6-72, +/-10.6%) for level III,
      respectively. V90 values (volume receiving 90% of dose) for the three techniques
      were 49% (43-53, +/-2.7%), 57% (51-65, +/-3.1%) and 73% (65-80, +/-3.4%) for
      level I (IMRT vs. ST; p = 0.029); 35% (26-42, +/-4.7%), 41% (33-50, +/-4.2%) and
      25% (17-36, +/-4.5%) for level II (IMRT vs ST; p = 0.068); and 15% (9-22, +/
      3.4%), 16% (10-24, +/-3.7%) and 8 (5-12, +/-3.1%) for level III (IMRT vs ST; p =
      0.039), respectively. CONCLUSION: Axillary levels I and II (lower axilla) receive
      substantial amount of incidental radiation doses with all the three techniques;
      however, conformal techniques (IMRT, 3DCRT) deliver significantly lesser
      incidental radiation to lower axilla than ST technique.

PMID- 24012149
TI  - Shiga toxin-producing Escherichia coli strains from cattle as a source of the
      Stx2a bacteriophages present in enteroaggregative Escherichia coli O104:H4
      strains.
AB  - Enteroaggregative, Shiga toxin-producing E. coli (EAEC-STEC) O104:H4 strains are
      emerging pathogens causing life threatening diseases in humans. EAEC-STEC O104:H4
      strains isolated between 2001 and 2011 were found to harbor a distinct type of
      Shiga toxin 2a- (Stx2a) encoding prophage. This phage type shows only <65%
      genetic similarity to so far described viable Stx phages due to differences in
      the modules for DNA replication, metabolism, regulation and host specificity. Stx
      production in EAEC is rarely observed and the source of the Stx2a phage in the
      EAEC-STEC O104:H4 strains is not known. We identified two DNA segments derived
      from orf15 and the cI gene of the O104:H4 Stx2a phage P13374 that are
      characteristic for Stx2a prophages present in EAEC-STEC O104:H4 strains. By PCR,
      these sequences were detected in 14 (5.8%) of 241 Stx2-positive STEC from animals
      and food. Infectious Stx2a phages could be isolated from four bovine STEC
      strains. These were found highly similar to P13374 for orf15, cI and stx2a
      sequences, the chromosomal integration site (wrbA), for phage DNA restriction
      profiles, virion morphology and superinfection immunity. Stx2a phages of the four
      bovine STEC strains formed lysogens on the E. coli K-12 strain C600. Phage P13374
      from an EAEC-STEC O104:H4 outbreak strain and one of the bovine STEC phages
      (P13803) lysogenized the Stx-negative EAEC O104:H4 strain CB14647 by integrating
      in the wrbA gene of CB14647 and converted it into a Stx2a producer. Our findings
      provide experimental evidence that EAEC-STEC O104:H4 strains have evolved by
      uptake of Stx2a phages from the bovine reservoir. 

PMID- 24012150
TI  - Recurrent IVF failure is associated with elevated progesterone on the day of hCG
      administration.
AB  - OBJECTIVE: During in vitro fertilization (IVF) treatment, elevated progesterone
      on the day of human chorionic gonadotrophin (hCG) administration has been
      reported to be associated with a reduced chance of live birth. It is not known,
      however, if the relationship is casual or causal. In the latter situation, one
      would expect the incidence of elevated progesterone on the day of hCG
      administration to increase with the number of IVF/embryo transfer (ET) failures.
      The aim of this study was to investigate if the frequency of elevated
      progesterone on the day of hCG administration is related to the number of IVF
      failures. STUDY DESIGN: This retrospective, observational, cohort study included
      a consecutive series of 6673 IVF cycles. Subjects were categorized into one of
      three groups: Group I, no previous IVF/ET treatment; Group II, one previous
      IVF/ET treatment failure; or Group III, two or more previous IVF/ET treatment
      failures. The main outcome measure was the proportion of cycles with elevated
      progesterone (>6 nmol/l) on the day of hCG administration. RESULTS: After
      adjusting for age, oestradiol level on the day of hCG administration and number
      of oocytes retrieved, the proportion of women with elevated progesterone on the
      day of hCG administration remained significantly different between the three
      groups: Group I, 16.8%; Group II, 31.7%; and Group III, 39.7% (p < 0.001).
      CONCLUSION: Elevated progesterone on the day of hCG administration is more likely
      in women with recurrent IVF failure. Women with two or more IVF failures are
      twice as likely to have elevated progesterone on the day of hCG administration as
      women undergoing their first IVF cycle.

PMID- 24012151
TI  - Censoring on outcome is not valid in self-controlled case series studies.

PMID- 24012152
TI  - Limitations of within-person study designs. In reply.

PMID- 24012154
TI  - n-3 PUFAs in cardiovascular disease.
AB  - Many large, randomised clinical trials and some meta-analyses have shown that
      treatment with n-3 polyunsaturated fatty acids (n-3 PUFAs) is associated with
      consistent benefits on cardiovascular (CV) events, primarily due to a reduction
      of coronary and CV deaths in patients with coronary heart disease. At variance
      with such evidence, some clinical trials and meta-analyses showing a neutral
      effect of n-3 PUFAs have been recently published, raising concern about the
      consistency of the evidence on the CV benefits of n-3 PUFAs. Several
      methodological and clinical aspects of these recent trials deserve to be
      considered. Indeed, the low rate of events or the overoptimistic expectations of
      the benefit of n-3 PUFAs used for sample size calculation led to an inadequate
      statistical power of several studies. The improvement of background medical
      therapy, serum baseline levels of n-3 PUFAs, and different doses and/or treatment
      duration might have downplayed the benefit of n-3 PUFAs. Similarly to old drugs
      shown to be effective some years ago, it is possible that the benefits of
      treatment with n-3 PUFAs are not as great in a modern CV prevention strategy so
      rich in many effective drugs compared with past trials testing CV drugs when less
      effective therapies were available. 

PMID- 24012153
TI  - Adipose tissue NK cells manifest an activated phenotype in human obesity.
AB  - OBJECTIVE: Adipose tissue inflammation is a cause of obesity-related metabolic
      disease. Natural killer (NK) cells are an understudied cell type in the context
      of obesity. The goal of this study was to determine the phenotype of human
      adipose tissue NK cells. METHODS: We used flow cytometry phenotyping to study
      adipose tissue and peripheral blood NK cells from obese and lean humans. RESULTS:
      Human adipose tissue NK cells, relative to peripheral blood NK cells, express
      increased levels of activation markers. Adipose tissue NK cells also demonstrate
      an activated phenotype in obese relative to lean subjects, with increased
      expression of the activating receptor NKG2D. CONCLUSIONS: These data are the
      first detailed phenotypic characterization of human adipose tissue NK cells, and
      suggest a role for NK cells in adipose tissue inflammation in obesity.

PMID- 24012155
TI  - Re-assessing the mechanism of action of n-3 PUFAs.
AB  - Recent evidence has been accumulated showing that use of dietary n-3
      polyunsaturated fatty acids (n-3 PUFAs) produces significant benefits in
      counteracting many disease states, including coronary atherosclerosis, fatal
      arrhythmias and heart failure. Besides the mass of proposed pathophysiological
      mechanisms underlying the potential benefits of using n-3 PUFAs, identification
      of clear molecular targets or an appropriate dosing strategy for these compounds
      still remain to be better elucidated. On the other hand, whilst n-3 PUFAs have
      shown promise in all of these areas, results arising from clinical trials and
      'real-world' evidence sometimes appear controversial. Here we report on recent
      advances in molecular targets identified for better assessment of the mode of
      action of these interesting compounds. In addition, some appealing hypotheses of
      their antioxidant properties will be discussed for better characterisation of
      their mode of action and potential use in health and disease. 

PMID- 24012156
TI  - Tricuspid annular plane systolic excursion is related to performance at six
      minute walking test in patients with heart failure undergoing exercise training.

PMID- 24012157
TI  - Long-term outcomes of percutaneous coronary intervention with stenting and
      coronary artery bypass graft surgery - a meta-analysis.

PMID- 24012158
TI  - From Rete Mirabile to Willis' circle, historical progress of medicine.

PMID- 24012159
TI  - n-3 PUFAs and heart failure.
AB  - The risk of death of patients with heart failure (HF) is still too high in daily
      clinical practice despite the many progress that have occurred in the diagnosis
      and treatment of this syndrome that significantly reduce the mortality of these
      patients. Results of the GISSI-HF trial, the first and only large-scale clinical
      trial to date assessing the effects of n-3 polyunsaturated fatty acids (n-3
      PUFAs) in HF patients, showed that treatment of 100 patients saved almost 2 lives
      and prevented almost 2 cardiovascular hospitalisations, indicating that
      beneficial cardiovascular effects of n-3 PUFAs observed in other populations
      might also apply to patients with HF. Treatment with n-3 PUFAs may be considered
      as a new option to add to the shortlist of evidence-based life-prolonging
      therapies for HF, as suggested by the recent guidelines of the European Society
      of Cardiology. However, further large clinical trials are undoubtedly needed to
      give adequate answers to still open questions on the treatment of HF. 

PMID- 24012160
TI  - The dipeptidyl peptidase-4 inhibitor-sitagliptin modulates calcium dysregulation,
      inflammation, and PPARs in hypertensive cardiomyocytes.
AB  - BACKGROUND: Hypertension induces cardiac dysfunction, calcium (Ca(2+))
      dysregulation, and arrhythmogenesis. Dipeptidyl peptidase (DPP)-4 inhibitors, an
      antidiabetic agent with anti-inflammation and anti-hypertension potential, may
      regulate peroxisome proliferator-activated receptors (PPARs)-alpha, -gamma, and 
      delta and Ca(2+) homeostasis. OBJECTIVE: The purpose of this study was to
      investigate whether DPP-4 inhibitor, sitagliptin, can modulate PPARs and Ca(2+)
      handling proteins in hypertensive hearts. METHODS: A Western blot analysis was
      used to evaluate protein expressions of myocardial PPAR isoforms, tumor necrosis
      factor (TNF)-alpha, interleukin (IL)-6, sarcoplasmic reticulum ATPase (SERCA2a),
      Na(+)-Ca(2+) exchanger (NCX), ryanodine receptor (RyR), voltage-dependent Ca(2+)
      (CaV1.2), slow-voltage potassium currents (Kvs), angiotensin II type 1 receptor
      (AT1R), and receptor of advanced glycated end-products (RAGE) from Wistar-Kyoto
      (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with
      sitagliptin (10mg/kg for 4weeks). Conventional microelectrodes were used to
      record action potentials (APs) in the ventricular myocytes from each group.
      RESULTS: Compared to the control group, SHR had lower cardiac PPAR-alpha and PPAR
      delta protein expressions, but had greater cardiac PPAR-gamma levels, and TNF
      alpha, IL-6, RAGE, and AT1R protein expressions, which were ameliorated in the
      sitagliptin-treated SHR. SHR had prolonged QT interval and AP duration with less
      SERCA2a and RyR, and greater CaV1.2 expressions, which were also attenuated in
      sitagliptin-treated SHR. CONCLUSIONS: Sitagliptin significantly changed the
      cardiac electrophysiological characteristics and Ca(2+) regulation, which may
      have been caused by its effects on cardiac PPARs, proinflammatory cytokines, and
      AT1R.

PMID- 24012161
TI  - Endothelial microparticles exert differential effects on functions of Th1 in
      patients with acute coronary syndrome.
AB  - BACKGROUND: Endothelial microparticles (EMPs) can be involved in inflammatory
      process, blood coagulation, and regulation of vascular function. However, it
      remains unclear whether EMPs participate in the pathogenesis of ACS. The purpose
      of this study is to investigate the impact of EMPs on Th1/Th2 development and
      functions in vitro. METHODS: Eight-five patients were allocated into SAP group
      (n=27), UAP group (n=28), and AMI group (n=30). Twenty hospitalized patients with
      normal coronary angiography were recruited as controls. The frequency of EMPs,
      IFN-gamma, and IL-4 levels were measured, and the correlation between EMPs and
      Th1/Th2 cytokine was analyzed. PBMCs isolated from patients with ACS were treated
      in vitro with EMPs. This was followed by flow cytometry for Th1/Th2 counts, real
      time PCR and western blotting for T-bet and GATA mRNA and protein expression, and
      ELISA for IFN-gamma, TNF-alpha, IL-4, and IL-10. RESULTS: This study proved that
      the frequency of EMPs was significantly increased in ACS patients. There was a
      significant positive correlation between EMPs and IFN-gamma. EMPs could
      significantly upregulate the differentiation and function of Th1 through
      increasing the expression of T-bet mRNA and protein. Furthermore, this study also
      indicated that EMP treatment in vitro could promote the expression of TNF-alpha,
      which exerts adverse effects on the pathogenesis and progression of
      atherosclerosis. CONCLUSIONS: EMPs may be involved in the immune and inflammatory
      processes that take part in artery atherosclerosis and that they do so by
      regulating Th1/Th2 differentiation and function. They may play an important role
      in the pathogenesis of coronary atherosclerosis and plaque instability.

PMID- 24012162
TI  - Attitudes towards help-seeking and stigma among young people at risk for
      psychosis.
AB  - The role of self-labeling as 'mentally ill' and of stigma-related stress for help
      seeking among young people at risk for psychosis is unknown. Stronger self
      labeling and less stigma stress predicted better attitudes towards psychiatric
      medication and psychotherapy, controlling for clinical and sociodemographic
      variables. Interventions could target stigma-related stress to increase help
      seeking. 

PMID- 24012163
TI  - Iowa Gambling Task scores predict future drug use in bipolar disorder outpatients
      with stimulant dependence.
AB  - Poor decision-making is associated with poor recovery in persons with bipolar
      disorder and drug relapse in persons with stimulant dependence. Cognitive
      predictors of stimulant use in those with comorbid bipolar and stimulant
      dependence are surprisingly absent. Our goal was to determine if a single
      baseline assessment of decision-making (Iowa Gambling Task, IGT) would predict
      future drug use in bipolar disorder outpatients with comorbid stimulant
      dependence. Ninety-four men and women of multiple race/ethnic origins consented
      to participate in a 20-week study. Data analyses were performed on 63 comorbid
      bipolar outpatients completing at least four study weeks and 28 cocaine dependent
      volunteers without a mood disorder who participated as cocaine controls. There
      were no significant differences in IGT scores between comorbid patients and
      cocaine controls. In the comorbid group, IGT scores significantly predicted
      future drug use during the study. Age, sex, race, years of mental illness, or
      mood state did not significantly influence IGT scores. This is the first
      longitudinal study to show that IGT scores obtained at a single baseline
      assessment predicts future objective drug use in comorbid bipolar disorder
      outpatients with cocaine or methamphetamine dependence. Evaluating decision
      making with the IGT may provide clinicians with valuable insight about the
      trajectory of their patients' risk for future drug use. These data suggest a need
      to augment existing treatment with cognitive restructuring to prevent slips and
      relapses in comorbid bipolar patients. The lack of a bipolar control group and a
      modest sample size may limit data interpretations. 

PMID- 24012164
TI  - Cost analysis of risperidone long-acting injection in the treatment of
      schizophrenia and schizoaffective disorders in Hong Kong: an approach using
      generalised estimating equations.
AB  - Schizophrenia is one of the most expensive psychiatric illnesses. This study
      compared retrospectively health-care resources consumed 12 months before and 24
      months after risperidone long-acting injection (RLAI) treatment in Hong Kong. A
      mirror-image analysis was conducted using data (N=191) from three public
      hospitals in Hong Kong from 2003 to 2007. The main outcome measure was
      hospitalisation cost. Other secondary outcomes such as hospitalisation episodes,
      outpatient visits and adverse events were also compared. A predictive model was
      established using linear regression based on generalised estimating equations.
      Analysis showed that RLAI was associated with a reduction in hospitalisation cost
      by HK$10,001,390 (24.7%) (HK$40,418,694 vs. HK$30,417,303; P-value <0.05). Days
      of hospitalisation were reduced by 1538 days (10.1%) (15,271 vs. 13,733; P-value
      <0.05). The predictive model estimated that the hospitalisation cost of patients
      using RLAI was only 11.1% (3.1-3.93%, 95% confidence interval (CI)) compared to
      those receiving conventional antipsychotics combined with oral risperidone. Cost
      of hospitalisation was significantly reduced after RLAI therapy. However, results
      should be considered as indicative or suggestive only, due to potential
      channelling bias where certain drug regimens are preferentially prescribed to
      patients with particular conditions. The findings from our study may be useful in
      health-care decision making considering treatment options for schizophrenia in
      resource-limited settings. 

PMID- 24012165
TI  - Medical liability in surgery for morbid obesity by adjustable gastric band: nine
      case reviews.
AB  - Adjustable gastric banding is recognized for its effectiveness in obtaining long
      term weight loss with low morbidity-mortality for patients with morbid obesity.
      However, life-threatening complications can sometimes occur, and surgeons may end
      up in court. We analyzed complications, some of them lethal, arising from gastric
      banding surgery in nine patients and the main issues identified by the experts,
      contributing to the judge's decision. Gastric banding is considered a benign
      operation, but, of the nine cases examined herein, five resulted in death while
      the other four had serious consequences with several damages, especially
      aesthetic and psychological suffering. Perforations of the oesophagus or stomach
      remain the leading causes of complications; the experts identified several issues
      from the records that helped the judge to render a decision and condemn seven of
      the nine surgeons. Three types of faults were considered the responsibility of
      the doctors: the lack of patient information or incomplete medical records, a
      clumsy mistake or delay of appropriate treatment due to underestimation of
      clinical symptoms, and finally, failure to observe the proper indications. Expert
      opinion focused most often on criticism of postoperative behaviour and failure to
      make decisions according to the state of the art. 

PMID- 24012166
TI  - Trauma and cultural safety: providing quality care to HIV-infected women of
      aboriginal descent.
AB  - In Canada, the Aboriginal community is most at risk for HIV infection. Aboriginal
      peoples have disproportionately high rates of violence, drug use, and challenging
      socioeconomic circumstances. All of this is related to a history of colonization
      that has left Aboriginal people vulnerable to HIV infection through unsafe sex,
      needle sharing, and lack of access to health promotion and education. Aboriginal
      women are at particular risk for HIV infection. They experience a
      disproportionate degree of trauma, which is associated with colonization, high
      rates of childhood sexual abuse, and illicit drug use. A history of trauma
      impacts on access to health care, uptake of antiretroviral therapy, and mortality
      and morbidity in people with HIV. We describe the case of a 52-year-old, HIV
      infected Aboriginal woman. We review the current evidence related to her case,
      including colonization, intersectionality, post-traumatic stress disorder,
      depression, revictimization, and substance use. 

PMID- 24012167
TI  - Epstein-Barr virus-positive cytotoxic T-cell lymphoma followed by chronic active
      Epstein-Barr virus infection-associated T/NK-cell lymphoproliferative disorder: a
      case report.
AB  - A 30-year-old female patient presented with intestinal Epstein-Barr virus (EBV)
      positive cytotoxic T-cell lymphoma (EBV+ CTL), which was surgically resected.
      Fourteen years later, she returned to our hospital with hypersensitivity to
      mosquito bites and was diagnosed with chronic active EBV infection-associated
      T/NK-cell lymphoproliferative disorder (CAEBV/TNK-LPD). She developed systemic
      EBV+ CTL at age 47 years during the 2.5-year clinical course of CAEBV/TNK-LPD,
      despite multiagent chemotherapy and allogeneic stem cell transplantation.
      Afterward, she had a rapidly deteriorating clinical course and died at age 48
      years. The immunophenotype of the EBV+ CTL was consistently a CD3, CD8, and
      cytotoxic molecule-positive type with the same clonality in polymerase chain
      reaction analysis of T-cell receptor-gamma chain gene rearrangement. This is the
      first reported case of EBV+ CTL preceding the clinical presentation of CAEBV/TNK
      LPD. The present case was unique in suggesting a close relationship between EBV+
      CTL and chronic active EBV infection. 

PMID- 24012168
TI  - Is the UNB test reliable and valid for use with adults with upper limb
      amputation?
AB  - STUDY DESIGN: Clinical measurement. INTRODUCTION: The University of New Brunswick
      (UNB) Test of Prosthetic Function was developed for children. No studies have
      examined its use with adults. PURPOSE OF THE STUDY: Our purposes were to utilize
      the UNB with adults to examine test-retest, inter-rater reliability and examine
      validity. METHODS: The UNB was administered to 51 subjects. Forty-five completed
      it twice within 1 week. Internal consistency was examined. Test-retest
      reliability and inter-rater reliability were estimated. ANOVAs compared scores by
      prosthetic use. Correlations between UNB scales, 2 dexterity tests (the Modified
      Box and Block Test, the modified Jebsen-Taylor Hand Function Test), and the self
      reported Upper Extremity Functional Scale (UEFS) were examined. RESULTS: Alphas
      were 0.74-0.75 and 0.69-9.79 for spontaneity and skill respectively. ICCs for
      test-retest reliability and inter-rater reliability were 0.73, 0.76 for
      spontaneity and 0.76 and 0.79 for skill. There were no differences in scores by
      prosthetic experience. UNB correlations with dexterity measures were moderate,
      and correlations with UEFS were weak for spontaneity and non-significant for
      skill. CONCLUSIONS: UNB scales had acceptable reliability and preliminary
      evidence of validity for adults. LEVEL OF EVIDENCE: IIb.

PMID- 24012169
TI  - Novel mastadenovirus infection and clinical disease in a pygmy marmoset
      (Callithrix [Cebuella] pygmaea).
AB  - We describe the detection and successful isolation of a novel mastadenovirus from
      a pygmy marmoset (Callithrix [Cebuella] pygmaea) that died following an episode
      of severe respiratory signs. Pathologic/histopathologic examination revealed
      hydrothorax and catarrhal bronchopneumonia with pronounced desquamation of the
      bronchiolar epithelial cells, while in other airways a marked hyperplasia of the
      epithelial lining and numerous giant cells could be observed. We obtained partial
      sequence data from the adenoviral DNA-dependent DNA-polymerase gene of the
      isolated strain and analyses of this region showed the highest level of identity
      to the recently described bat adenoviruses (strains PPV1 and TJM) and the type 2
      canine adenovirus. Similar results were gained by phylogenetic calculations
      indicating that this novel marmoset adenovirus is only distantly related to
      reference Old and New World primate adenoviruses and formed a monophyletic group
      with bat and canine adenoviruses and the equine adenovirus 1. Even though the
      source of the infection remained unknown, our results could imply the possibility
      of a cross-species transmission of the virus from an anonymous host to the pygmy
      marmoset. 

PMID- 24012170
TI  - Acute kidney injury and long-term risk of stroke after coronary artery bypass
      surgery.
AB  - BACKGROUND: Acute kidney injury (AKI) is associated with death, end-stage renal
      disease, and heart failure in patients with coronary heart disease. This study
      investigated the association between AKI and long-term risk of stroke. METHODS
      AND RESULTS: 50,244 patients who underwent coronary artery bypass grafting (CABG)
      in Sweden between 2000 and 2008 were identified from the SWEDEHEART registry.
      After exclusions 23,584 patients without prior stroke who underwent elective,
      primary, isolated, CABG were included. AKI was categorized according to absolute
      increases in postoperative creatinine values compared with preoperative values:
      stage 1, 0.3-0.5 mg/dL (26-44 MUmol/L); stage 2, 0.5-1.0mg/dL (44-88 MUmol/L);
      and stage 3, >1.0 mg/dL (>=88 MUmol/L). Cox proportional hazards regression was
      used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for
      stroke. There were 1156 (4.9%) strokes during a mean follow-up of 4.1 years.
      After adjustment for confounders, HRs (95% CIs) for stroke in AKI stages 1, 2 and
      3 were 1.12 (0.89-1.39), 1.31 (1.04-1.66) and 1.31 (0.92-1.87), respectively,
      compared with no AKI. This association disappeared after taking death into
      account in competing risk analysis. There was a significant association between
      AKI and stroke in men (HR: 1.26 [1.05-1.50]) but not in women (HR: 1.07 [0.75
      1.53]), and in younger (<65 years; HR: 1.57 [1.12-2.22]), but not elderly
      patients (HR: 1.17 [0.98-1.40]). CONCLUSIONS: The long-term risk of stroke is
      weakly associated with AKI after primary isolated CABG, but this association is
      attenuated and not significant when considering death as a competing risk.

PMID- 24012171
TI  - Distinct prognostic impacts of both atrial volumes on outcomes after
      radiofrequency ablation of nonvalvular atrial fibrillation: three-dimensional
      imaging study using multidetector computed tomography.
AB  - BACKGROUND: Left atrial (LA) enlargement is associated with atrial fibrillation
      (AF) recurrence after radiofrequency ablation (RFA). However, impact of right
      atrial (RA) size on outcomes after RFA is unclear. METHODS: Patients who
      underwent RFA of AF (n=242, 197 men, 57 +/- 11 years) were enrolled (159
      paroxysmal [PaAF] and 83 persistent [PeAF]). Three-dimensional RA and LA volumes
      were measured before RFA with multidetector computed tomography and indexed to
      body surface area (RAVI and LAVI). RESULTS: After a 3-month blanking period, 66
      patients (27%) failed to maintain sinus rhythm during follow-up (556 +/- 322
      days). Despite similar clinical characteristics, LAVI was larger (77 +/- 21 vs.
      91 +/- 27 ml/m(2), P<0.001) and RAVI showed a trend to be greater (85 +/- 26 vs.
      92 +/- 25 ml/m(2), P=0.06) in patients with future recurrence than without
      recurrence. Additionally, patients with larger RA or LA experienced recurrences
      more frequently and earlier during follow-up (log rank, P < 0.05 for all). In Cox
      regression analysis, LAVI was independently associated with outcomes (10 ml/m(2)
      increase; HR: 1.22, 95% CI: 1.09-1.36, P<0.001), whereas RAVI was not. In
      subgroup analysis, 25 PaAF patients (16%) experienced recurrence and both atrial
      volumes failed to predict the outcome independently, despite borderline
      significance of RAVI (10 ml/m(2) increase; HR: 1.21, 95% CI: 1.00-1.48, P=0.05).
      Meanwhile, 41 patients (49%) in PeAF group experienced AF recurrence and LAVI was
      an independent prognosticator (10 ml/m(2) increase; HR: 1.19, 95% CI: 1.03-1.36).
      CONCLUSIONS: RA size might affect the outcome after RFA in PaAF patients. LA
      enlargement, rather than RA size, influence outcomes after RFA, especially in
      PeAF.

PMID- 24012172
TI  - Does obesity amplify the association between ambient air pollution and increased
      blood pressure and hypertension in adults? Findings from the 33 Communities
      Chinese Health Study.

PMID- 24012173
TI  - Serum potassium levels and the risk of atrial fibrillation: the Rotterdam Study.
AB  - BACKGROUND: Atrial fibrillation is the most common sustained arrhythmia in the
      elderly. Serum potassium is associated with ventricular arrhythmias and cardiac
      arrest. Little is known about the association of serum potassium with atrial
      fibrillation. The objective of this study was to investigate the association of
      serum potassium and the risk of atrial fibrillation in a population based
      setting. METHODS: The study was performed within the prospective population-based
      Rotterdam Study. The study population consisted of 4059 participants without
      atrial fibrillation at baseline for whom baseline levels of serum potassium were
      measured. Atrial fibrillation was ascertained from centre visit ECG assessments
      as well as medical records. RESULTS: During a mean follow up of 11.8 years
      (SD=5.2 yr), 474 participants developed atrial fibrillation. Participants with
      hypokalemia (<3.5 mmol/l) had a higher risk of atrial fibrillation (HR: 1.63,
      95%CI: 1.03-2.56) than those with normokalemia (3.5-5.0 mmol/l). This association
      was independent of age, sex, serum magnesium, and other potential confounders.
      Especially in participants with a history of myocardial infarction, those with
      hypokalemia had a higher risk of atrial fibrillation than those with normokalemia
      (HR: 3.81, 95%-CI: 1.51-9.61). CONCLUSIONS: In this study low serum levels of
      potassium were associated with a higher risk of atrial fibrillation.

PMID- 24012175
TI  - Biomechanical evaluation of a new MatrixMandible plating system on cadaver
      mandibles.
AB  - PURPOSE: Current mandibular plating systems contain a wide range of plates and
      screws needed for the treatment of mandibular reconstruction and mandibular
      fractures. The authors' hypothesis was that a single diameter screw could be used
      in all applications in a plating system. Therefore, the purpose of this study was
      to test if the 2.0-mm locking screws could replace the 2.4-mm screws to stabilize
      a 2.5-mm-thick reconstruction plate in the treatment of mandibular discontinuity.
      MATERIALS AND METHODS: Thirty-six fresh human cadaveric mandibles were used: 18
      were plated using 2.0-mm locking screws (experimental) and the other 18 were
      plated using 2.4-mm locking screws (control). Each group was further divided into
      3 subgroups based on the site of loading application: the ipsilateral (right)
      second premolar region, the central incisal region, and the contralateral (left)
      first molar region. The same ipsilateral (right) mandibular angular discontinuity
      was created by the same surgeon. The mandible was mounted on a material testing
      machine. The micromotions between the 2 segments, permanent and elastic
      displacements, were recorded after incremental ramping loads. The magnitude of
      screw back-out and the separation between plate and bone were recorded using a
      laser scanner (resolution, 0.12 mm) before and after the loading applications.
      The data were processed. Descriptive analyses and a general linear model for
      repeated measures analysis of variance were performed. RESULTS: There was no
      statistically significant difference in permanent displacement (mean, 1.16 and
      0.82 mm, respectively) between the 2.0-mm and 2.4-mm screw groups. There also was
      no statistically significant difference in elastic displacement between the 2
      groups (mean, 1.48 and 1.21 mm, respectively). Finally, there were no
      statistically significant differences in screw back-out or separation between
      plate and bone between the 2 groups. All means for screw back-out and separation
      between screw and bone for each group were judged within the error of the laser
      scanning system (<0.12 mm). CONCLUSION: One may anticipate that the mechanical
      functions of the 2.0-mm locking screws are not different from those of the 2.4-mm
      screws when a 2.5-mm-thick reconstruction plate is used to reconstruct mandibular
      angular discontinuity. However, further biomechanical studies (ie, fatigue of
      screws) are warranted before a randomized clinical trial can be conducted to
      definitively prove that the 2.4-mm screws can be replaced by 2.0-mm screws.

PMID- 24012176
TI  - Activation of kynurenine pathway in ex vivo fibroblasts from patients with
      bipolar disorder or schizophrenia: cytokine challenge increases production of 3
      hydroxykynurenine.
AB  - Accumulating data suggest a causative link between immune stimulation, disturbed
      metabolism of tryptophan, and pathogenesis of bipolar disorder and schizophrenia.
      The goal of this study was to examine the production of kynurenic acid (KYNA), 3
      hydroxykynurenine (3-HK) and the expression of kynurenine pathway enzymes
      involved in their synthesis and metabolism in cultured skin fibroblasts obtained
      from patients with bipolar disorder, schizophrenia or from healthy control
      individuals. The assessment was performed under basal conditions or following
      treatment with interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-1beta, IL-6, or their combinations, in cells exposed to
      exogenous kynurenine. In both groups of patients, the baseline production of KYNA
      and 3-HK was increased, as compared to control subjects. Case-treatment analyses
      revealed significant interactions between bipolar case status and IL-1beta, IL-6,
      IFN-gamma + TNF-alpha, or IFN-gamma + IL-1beta, as well as between schizophrenia
      case status and IL-1beta, IFN-gamma + TNF-alpha, or IFN-gamma + IL-1beta, in
      terms of higher 3-HK. Noteworthy, no case-treatment interactions in terms of KYNA
      production were found. Observed changes did not appear to correlate with the
      expression of genes encoding kynurenine aminotransferases (KATs), kynureninase
      (KYNU) or kynurenine-3-monooxygenase (KMO). The single nucleotide polymorphisms
      (SNPs), rs1053230 and rs2275163, in KMO influenced KYNA levels yet did not
      explain the case-treatment discrepancies. In conclusion, our present findings
      indicate the utility of skin-derived fibroblasts for kynurenines research and
      support the concept of kynurenine pathway alterations in bipolar disorder and
      schizophrenia. The increase in ratio between neurotoxic 3-HK and
      neuroinhibitory/neuroprotective KYNA following exposure to cytokines may account
      for altered neurogenesis and structural abnormalities characteristic for both
      diseases.

PMID- 24012174
TI  - Changes in reperfusion strategy over time for ST segment elevation myocardial
      infarction in the Greater Paris Area: results from the e-MUST Registry.
AB  - BACKGROUND: ESC guidelines recommend a shorter (90 min) delay for the use of
      primary percutaneous intervention (pPCI) in patients presenting within the first
      2h of pain onset. Using registry data on STEMI patients in the Greater Paris
      Area, we assessed changes between 2003 and 2008 in the rates of pPCI, pre
      hospital fibrinolytic therapy (PHF) and time delays in patients presenting within
      2h of STEMI pain onset. METHODS: The Greater Paris Area was divided in 3 regions:
      Paris, the small and large rings. Patients were divided in three groups according
      to their reperfusion strategy: a) PHF, b) timely pPCI (FMC to balloon inflation
      time < 90 min), and c) late pPCI (FMC to balloon inflation time > 90 min).
      RESULTS: Among the 5592 patients included, 1695 (39%) had PHF, 1266 (29%) had
      timely pPCI, and 1415 (32%) had late pPCI. Over the 6 years, there was a sharp
      increase in timely pPCI in all regions, balanced by a decrease in PHF. The rate
      of late pPCI remained globally stable, with a decrease in Paris, stabilization in
      the small ring, and an increase in the large ring, where the density of
      catheterization laboratories was the lowest. By multivariate analysis, using on
      time pPCI as a reference group, mortality was higher in the PHF and late pPCI
      groups. CONCLUSIONS: In areas with a low density of pPCI centers, efforts should
      be made to improve the timeliness of pPCI. Otherwise, PHF followed by an
      immediate transfer to a pPCI capable hospital may be considered.

PMID- 24012177
TI  - The cost-effectiveness of immunochemical tests for colorectal cancer screening.
AB  - BACKGROUND: The optimal immunochemical test to use for generalised mass screening
      is still under debate in France. AIM: To compare the cost and effectiveness in
      biennial screening for colorectal cancer of fifteen strategies consisting of the
      three-stool sample un-rehydrated guaiac faecal occult blood test and three
      immunochemical tests: Magstream, FOB-Gold and OC-Sensor, at different positivity
      cut-off levels and stool-sample collection. METHODS: A Markov model was used to
      compare these strategies in a general population of 100,000 individuals aged 50
      74 over a 20-year period. RESULTS: Immunochemical tests were efficient strategies
      compared with guaiac faecal occult blood test. When all 15 strategies were
      compared with each other, only five of them remained efficient: the one- and two
      stool sample Magstream, the one- and two-stool sample FOB-Gold with the 176 ng/mL
      cut-off, and the two-stool sample OC-Sensor with the 150 ng/mL cut-off.
      Sensitivity analyses showed that, at an identical price, the one-stool sample OC
      Sensor was the most efficient strategy, and outperformed FOB-Gold. CONCLUSION:
      One-stool immunochemical testing can be considered a promising alternative to the
      guaiac faecal occult blood test for colorectal cancer mass screening in the
      general population. Competition between manufacturers should now be introduced to
      reduce purchase price differences.

PMID- 24012178
TI  - Changes in plasma steroid levels during oocyte development in Indian shad,
      Tenualosa ilisha (Hamilton, 1822): role of gonadotropins on in vitro steroid
      production and development of oocyte maturational competence.
AB  - Circanual variations in plasma testosterone (T), 17-estradiol (E2), and 17,20
      dihydroxy-4-pregnen-3-one (17,20-P) levels and ovarian steroid synthetic
      potential of Tenualosa ilisha of river Hooghly, West Bengal, India were examined.
      This fish exhibited bi-annual spawning; one during April-May and another during
      August-September. Coinciding with the GSI values, present study recorded a
      decline in plasma T and E2 levels from October, reaching their lowest values in
      January followed by a rapid rise in March when the ovary contained mostly
      vitellogenic follicles and remained high up to April (postvitellogenic stage).
      Plasma 17,20beta-P level was detected in March and reached peak value in April
      during oocyte maturation. After spawning, all the steroid levels declined to
      reach lowest values in June. From June onwards, T and E2 levels again increased
      for the next cycle and peaked at the end of vitellogenesis. Plasma 17,20beta-P
      was reappeared in August and reached maximum in September during oocyte
      maturation and spawning. Of the two gonadotropins tested, in vitro production of
      both T and E2 by the vitellogenic and postvitellogenic follicles was regulated by
      FSH and LH respectively. Production of 17,20-P by the post-vitellogenic follicles
      was regulated by LH only. Acquisition of in vitro oocyte maturational competence
      (OMC) was developed by the addition of HCG in culture medium. Treatment of a
      3beta-HSD inhibitor blocked LH-induced steroid production, but not development of
      OMC. Both Cycloheximide and actinomycin D inhibited LH-induced development of
      OMC, indicating the requirement of de novo protein synthesis for this process. 

PMID- 24012179
TI  - Calix[4]arene methylenebisphosphonic acids as inhibitors of protein tyrosine
      phosphatase 1B.
AB  - Salix[4]arenes bearing methylenebisphosphonic or hydroxymethylenebisphosphonic
      acid fragments at the wide rim of the macrocycle were studied as inhibitors of
      PTP1B. Some of the inhibitors showed IC50 values in the micromolar range and good
      selectivity in comparison with other protein tyrosine phosphatases such as TC
      PTP, PTPbeta, LAR, and CD45. Kinetic studies indicated that the calix[4]arene
      derivatives influence PTP1B activity as slow-binding inhibitors. Based on
      molecular docking results, the binding modes of the macrocyclic bisphosphonates
      in the active centre of PTP1B are discussed. 

PMID- 24012180
TI  - The synthesis and SAR study of phenylalanine-derived (Z)-5-arylmethylidene
      rhodanines as anti-methicillin-resistant Staphylococcus aureus (MRSA) compounds.
AB  - A focused library of rhodanine compounds containing novel substituents at the C5
      position was synthesized and tested in vitro against a panel of clinically
      relevant MRSA strains. The present SAR study was based on our lead compound 1
      (MIC=1.95 MUg/mL), with a focus on identifying optimal C5-arylidene substituents.
      In order to obtain this objective, we condensed several unique aromatic aldehydes
      with phenylalanine-derived rhodanine intermediates to obtain C5-substituted
      target rhodanine compounds for evaluation as anti-MRSA compounds. These efforts
      produced three compounds with significant efficacy: 23, 32 and 44, with MIC
      values ranging from 0.98 to 1.95 MUg/mL against all tested MRSA strains as
      compared to the reference antibiotics penicillin G (MIC=15.60-250.0 MUg/mL) and
      ciprofloxacin (MIC=7.80-62.50 MUg/mL) and comparable to that of vancomycin
      (MIC=0.48 MUg/mL). In addition, compounds 24, 28, 37, 41, 46 and 48 (MIC=1.95
      3.90 MUg/mL) were efficacious against all MRSA strains. The majority of the
      synthesized compounds had bactericidal activity at concentrations only two to
      fourfold higher than their MIC. Overall, the results suggest that compounds 23,
      32 and 44 may be of potential use in the treatment of MRSA infections.

PMID- 24012181
TI  - Synthesis and biological evaluation of novel 3,4-diaryl lactam derivatives as
      triple reuptake inhibitors.
AB  - A series of 3,4-diarylpyrrolidin-2-one was designed, prepared and evaluated as
      triple reuptake inhibitors for antidepressant. Most compounds exhibited
      comparable in vitro efficacy as norepinephrine and dopamine transporter reuptake
      inhibitors. Especially, 2i showed better potency than GBR-12909 (IC50=14 nM)
      which was used as reference compound for dopamine transporter. In addition, 2a
      and 2b showed inhibition (5.17 MUM-85.6 nM) for three transporters.

PMID- 24012182
TI  - Inhibition of monoamine oxidase by 3,4-dihydro-2(1H)-quinolinone derivatives.
AB  - In the present study, a series of 3,4-dihydro-2(1H)-quinolinone derivatives were
      synthesized and evaluated as inhibitors of recombinant human monoamine oxidase
      (MAO) A and B. The 3,4-dihydro-2(1H)-quinolinone derivatives are structurally
      related to a series of coumarin (1-benzopyran-2-one) derivatives which have been
      reported to act as MAO-B inhibitors. The results document that the quinolinones
      are highly potent and selective MAO-B inhibitors with most homologues exhibiting
      IC50 values in the nanomolar range. The most potent MAO-B inhibitor, 7-(3
      bromobenzyloxy)-3,4-dihydro-2(1H)-quinolinone, exhibits an IC50 value of 2.9 nM
      with a 2750-fold selectivity for MAO-B over the MAO-A isoform. An analysis of the
      structure-activity relationships for MAO-B inhibition shows that substitution on
      the C7 position of the 3,4-dihydro-2(1H)-quinolinone scaffold leads to
      significantly more potent inhibition compared to substitution on C6. In this
      regard, a benzyloxy substituent on C7 is more favourable than phenylethoxy and
      phenylpropoxy substitution on this position. It may be concluded that C7
      substituted 3,4-dihydro-2(1H)-quinolinones are promising leads for the therapy of
      Parkinson's disease.

PMID- 24012183
TI  - Identification of 2-amino-5-aryl-pyrazines as inhibitors of human lactate
      dehydrogenase.
AB  - A 2-amino-5-aryl-pyrazine was identified as an inhibitor of human lactate
      dehydrogenase A (LDHA) via a biochemical screening campaign. Biochemical and
      biophysical experiments demonstrated that the compound specifically interacted
      with human LDHA. Structural variation of the screening hit resulted in
      improvements in LDHA biochemical inhibition and pharmacokinetic properties. A
      crystal structure of an improved compound bound to human LDHA was also obtained
      and it explained many of the observed structure-activity relationships. 

PMID- 24012184
TI  - Efforts toward broadening the spectrum of arylomycin antibiotic activity.
AB  - New antibiotics are needed, and one source may be 'latent' antibiotics, natural
      products whose once broad-spectrum activity is currently limited by the evolution
      of resistance in nature. We have identified a potential class of latent
      antibiotics, the arylomycins, which are lipopeptides with a C-terminal macrocycle
      that target signal peptidase and whose spectrum is limited by a resistance
      conferring mutation in many bacteria. Herein, we report the synthesis and
      evaluation of several arylomycin derivatives, and demonstrate that both C
      terminal homologation with a glycyl aldehyde and addition of a positive charge to
      the macrocycle increase the activity and spectrum of the arylomycin scaffold. 

PMID- 24012185
TI  - Synthesis and anti-inflammatory activity of three nitro chalcones.
AB  - The aim of this study was to synthesize three nitro substituted chalcones and to
      evaluate their anti-inflammatory activity in the model of carrageenan induced
      edema in rats. The nitro chalcone were prepared by aldol condensation using of
      mechanical agitation and environmentally friendly solvents with 72-73% yields in
      approximately 2h. The three structures were evaluated on biological activity at
      dose of 200mg/kg and they showed anti-inflammatory protective effect by both oral
      and intraperitoneal administration, this effect was time dependent. 

PMID- 24012186
TI  - Understanding the reasons why patients delay seeking treatment for oral cancer
      symptoms from a primary health care professional: an integrative literature
      review.
AB  - PURPOSE: The purpose of this integrative literature review was to investigate
      existing research on the reasons why patients delay in seeking treatment for oral
      cancer symptoms from a primary health care professional. METHOD: The systematic
      approach developed by Cooper (1984) was the guiding framework for this
      integrative review. Cooper (1984) identifies the process of conducting an
      integrative review as encompassing the following five stages: (a) problem
      formulation, (b) data collection, (c) evaluation of data points, (d) data
      analysis and interpretation, and (e) public presentation of results. RESULTS:
      Despite different research designs employed and sample sizes ranging from 15 to
      559, three major themes emerged from the 16 studies included in the review, all
      of which are directly related to the reasons why people delay seeking treatment
      for oral cancer symptoms: Patient Sociodemographic Characteristics; Health
      Related Behaviours, and Psychosocial Factors. CONCLUSIONS: Overall, this
      integrative review demonstrates the complexity surrounding the reasons why
      patients delay in seeking help for oral cancer treatment. The association between
      knowledge and patient delay has implications for information provision about
      cancer to those at risk of developing the disease. The relationship between
      socioeconomic status and patient delay behaviour warrants further investigation
      as this has been shown to be an influential factor in the study of patient delay.
      The meaning of many of the investigated psychosocial factors (e.g. an
      individuals' symptom interpretation/attribution, disclosure of symptoms to
      significant others, social priorities), have not been discussed in detail and the
      research is not theory driven.

PMID- 24012187
TI  - Understanding cancer patients' reflections on good nursing care in light of
      Antonovsky's theory.
AB  - PURPOSE: Data from an empirical study about cancer patients' perception of good
      caring are analysed in the light of Antonovsky's theory. The aim was to reflect
      on whether and how health personnel by giving good care, can function as vital
      resources at cancer patients disposal in activating their General Resistance
      Resources (GRRs) in a stressful life situation, and by that contribute to
      promotion and maintenance of their sense of coherence. METHODS AND SAMPLE: A
      hermeneutical approach was chosen for analysing the data. The informants were
      cancer patients in an oncology ward in a regional hospital in Norway. Twenty
      patients were interviewed, ten women and ten men. The patients had various cancer
      diagnoses at different stages and had different prognoses. KEY FINDINGS: The
      findings indicate that most of the patients succeeded in activating their GRRs in
      dealing with the stressor. Nurses, doctors, family and friends can be seen to
      function as vital resources at their disposal when needed. Most likely good
      caring supported the patient's promotion and maintenance of the components of
      meaningfulness, comprehensibility and manageability which form the concept sense
      of coherence (SOC). CONCLUSION: Health personnel can support the patients'
      meaningfulness by listening to the patients' stories about what still gives them
      meaning in life and their comprehensibility by giving good information.
      Alleviation of physical suffering may promote and maintain their manageability.
      Because all three components are intertwined, it is important to focus on all of
      them when caring for cancer patients.

PMID- 24012188
TI  - Structure and content in consultations with patients undergoing surgery for
      colorectal cancer.
AB  - PURPOSE: To explore the structure and content of pre-planned consultations as
      part of the care and treatment of patients undergoing surgery for colorectal
      cancer. METHODS: The study was based on 50 transcripts of audio-recorded pre
      planned consultations between seven patients and 36 healthcare professionals from
      the time of diagnosis, pre-operative consultation, discharge consultation and
      pathology report in a colorectal unit. RESULTS: The spread of consultation time
      between professions was considerable. Total mean consultation time for patients
      during the care process (7 consultations/patient) was 111 min (range 83-191). The
      mean consultation time for surgeons was 18 min (7-40), anaesthesiologists 12 min
      (5-18) and nurses 14 min (5-49). Patients took up 40% of the word space,
      healthcare professionals used 59% and significant others 1%. Word space changed
      in such a way that the patient became more active towards the final consultation.
      Neither during the diagnosis consultation nor during the pre-operative
      consultation did the patients meet the operating surgeon. Six major subjects
      emerged: general health, diagnosis, surgical procedure, pre-operative
      preparations, recovery and treatment and follow-up. CONCLUSIONS: There is a need
      for clearer structure in the consultations. Most consultations lacked a clear
      introduction to the subject of the conversation. The study makes it possible to
      develop methods and structure for supporting conversations in which the patient
      is given space to help with the difficult issues present after undergoing surgery
      for colorectal cancer. The study also contributes to providing knowledge of how
      to organise surgical consultations in order to optimise person-centeredness,
      teamwork and clinical efficiency.

PMID- 24012190
TI  - Variability in management of implantable ports in oncology outpatients.
AB  - PURPOSE OF THE RESEARCH: To describe the variability in practice regarding the
      management of vascular access ports in adult oncology patients at Spanish
      outpatient clinics and to evaluate its compliance with the recommended procedural
      guidelines. METHODS AND SAMPLE: Three e-mailings or three postal mail-outs were
      sent to all Spanish outpatient clinics, in accordance with the hospital's
      preference. An additional fourth postal mail-out was made to all units. In total
      185 units at Spanish outpatient clinics out of a total 256 completed the survey
      questionnaire. KEY RESULTS: A number of variations exist in the techniques used
      for insertion, withdrawal of needle from vascular access ports, blood sampling
      and unblocking procedure. There is considerable agreement in relation to the use
      of a special beveled needle, the use of gloves in the access and withdrawal
      procedures and checking of reservoir permeability by aspirating blood. In most
      cases, sterile gloves are used but there is a lesser occurrence of both scrubbed
      hands and correct antiseptic use. CONCLUSIONS: There are considerable differences
      in the management of the vascular access ports in terms of the recommendations
      published in the main international guidelines, though these are based on low
      level evidence. The results highlight the need for further quality studies in
      ports use and manipulation to lessen the variability between published
      recommendations and clinical practice.

PMID- 24012189
TI  - Differences in morning and evening fatigue in oncology patients and their family
      caregivers.
AB  - PURPOSE OF THE RESEARCH: To identify distinct latent classes of individuals based
      on ratings of morning and evening fatigue; evaluate for differences in phenotypic
      characteristics, as well as symptom and quality of life scores, among these
      latent classes; and evaluate for an overlap in morning and evening fatigue class
      membership. PATIENTS AND METHODS: In a sample of 167 oncology outpatients and 85
      of their FCs, growth mixture modeling was used to identify distinct latent
      classes based on ratings of morning and evening fatigue obtained before, during,
      and after radiation therapy. Analyses of variance and Chi Square analyses were
      used to evaluate for differences among the morning and evening fatigue latent
      classes. RESULTS: Three distinct latent classes for morning fatigue were
      identified. Participants in the High Morning Fatigue class (47%) were younger and
      had lower functional status. Three distinct latent classes for evening fatigue
      were identified. Participants in the High Evening Fatigue class (61%) were
      younger, more likely to be female, more likely to have children at home, and more
      likely to be a FC. Only 10.3% of participants were classified in both the Very
      Low Morning and Low Evening Fatigue classes and 41.3% were classified in both the
      High Morning and High Evening Fatigue classes. CONCLUSIONS: Different
      characteristics were associated with morning and evening fatigue, which suggests
      that morning and evening fatigue may be distinct but related symptoms. Additional
      research is needed to elucidate the mechanisms that may underlie diurnal
      variability in fatigue.

PMID- 24012191
TI  - Food caregivers influence on nutritional intake among admitted haematological
      cancer patients - a prospective study.
AB  - PURPOSE: Haematological cancer patients have an increased risk of
      undernourishment due to their malignancy, treatment toxicity and severe
      infections. This study examines whether kitchen assistants working as food
      caregivers increase nutritional intake and knowledge among haematological cancer
      patients. METHODS: Comparison of two cross-sectional studies with dietary
      assessment of patients with haematological malignancies before (N = 42) and after
      (N = 45) implementation of food caregivers. Secondly, a questionnaire concerning
      dietary counselling performed before (N = 74) and after (N = 78) the
      implementation. RESULTS: The energy requirements were fulfilled with 76.2% (CI
      95% 64.6-87.9) and 93.3% (CI 95% 82.3-104.3) of the calculated need in the before
      group and the after-group, respectively (p = 0.03). The improvement was mainly
      due to increased energy intake through between meal snacks served by the food
      caregivers. There was no difference in protein intake between the two groups. The
      study showed that more than two-thirds of the patients in both groups had side
      effects like fatigue, loss of appetite, vomiting, xerostomia or taste disorder to
      a degree that affected nutritional intake. When adjusted for side effects,
      patients in the after-group increased energy intake by 22% (CI 95% 6.1-38.0) (p =
      0.007). After implementation of food caregivers significantly more patients
      stated that they were informed about their nutritional needs, 41% in the before
      group and 67% in the after-group (p = 0.001). CONCLUSIONS: Educated and trained
      food caregivers working at the wards increase nutritional intake and knowledge
      among haematological cancer patients and play an important role in the multi
      professional nutritional management.

PMID- 24012192
TI  - Associations between cytokine gene variations and self-reported sleep disturbance
      in women following breast cancer surgery.
AB  - PURPOSE OF THE RESEARCH: To attempt to replicate the associations found in our
      previous study of patients and family caregivers between interleukin 6 (IL6) and
      nuclear factor kappa beta 2 (NFKB2) and sleep disturbance and to identify
      additional genetic associations in a larger sample of patients with breast
      cancer. METHODS AND SAMPLE: Patients with breast cancer (n = 398) were recruited
      prior to surgery and followed for six months. Patients completed a self-report
      measure of sleep disturbance and provided a blood sample for genomic analyses.
      Growth mixture modeling was used to identify distinct latent classes of patients
      with higher and lower levels of sleep disturbance. KEY RESULTS: Patients who were
      younger and who had higher comorbidity and lower functional status were more
      likely to be in the high sustained sleep disturbance class. Variations in three
      cytokine genes (i.e., IL1 receptor 2 (IL1R2), IL13, NFKB2) predicted latent class
      membership. CONCLUSIONS: Polymorphisms in cytokine genes may partially explain
      inter-individual variability in sleep disturbance. Determination of high risk
      phenotypes and associated molecular markers may allow for earlier identification
      of patients at higher risk for developing sleep disturbance and lead to the
      development of more targeted clinical interventions.

PMID- 24012193
TI  - Resistance to targeted therapies: a role for microRNAs?
AB  - The discovery of oncogene addiction dramatically changed the therapeutic approach
      for cancer treatment, and many drugs targeting specific molecular alterations are
      now in clinics. Despite the big success of these new compounds, the main limit to
      their efficacy is represented by resistance to therapy. The alteration of the
      activity or of the expression of many proteins has already been linked to the
      onset of resistance, but recent evidence indicates a role of microRNAs (miRNAs)
      as well. In this context, the idea of exploiting miRNAs as predictors of response
      or resistance to cancer therapy represents an intriguing possibility. The purpose
      of this review is to address the relationship between miRNAs and targeted
      therapies response and resistance. 

PMID- 24012194
TI  - Small RNAs and heritable epigenetic variation in plants.
AB  - Recent studies suggest that inheritance of phenotypes in plants is more likely to
      involve epigenetics than in mammals. There are two reasons for this difference.
      First, there is a RNA-based system in plants involving small (s)RNAs that
      influences de novo establishment and maintenance of DNA methylation at many sites
      in plant genomes. These regions of methylated DNA are epigenetic marks with the
      potential to affect gene expression that are transmitted between dividing cells
      of the same generation. Second, unlike mammals, DNA methyltransferases in plants
      are active during gametogenesis and embryogenesis so that patterns of DNA
      methylation can persist from parent to progeny and do not need to be reset. We
      discuss how the effects of stress and genome interactions in hybrid plants are
      two systems that illustrate how RNA-based mechanisms can influence heritable
      phenotypes in plants. 

PMID- 24012195
TI  - Peripheral natural killer cell activity as a predictor of recurrent pregnancy
      loss: a large cohort study.
AB  - OBJECTIVE: To determine the predictive value of preconceptional peripheral blood
      natural killer (pNK) cell activity in patients with recurrent pregnancy loss
      (RPL). DESIGN: Cohort study. SETTING: University department. PATIENT(S): A total
      of 552 patients with a history of two to six consecutive miscarriages.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The predictive value of
      preconceptional pNK cell activity for subsequent miscarriage was analyzed using
      multivariable logistic regression analysis, with age, number of previous
      miscarriages, and presence/absence of previous live births and bed rest as
      covariates. RESULT(S): Age and number of previous miscarriages, but not high pNK
      cell activity, were found to be independent risk factors for a subsequent
      miscarriage. No effect of bed rest and previous live birth on the likelihood of
      live birth was observed (odds ratios 1.28 [95% confidence interval 0.81-2.02] and
      0.91 [0.52-1.59], respectively). CONCLUSION(S): Elevated pNK cell activity was
      found to not be an independent risk factor for subsequent miscarriage. Clinicians
      should not measure the plasma NK activity as a systematic recurrent pregnancy
      loss examination, because its clinical significance is yet to be established.

PMID- 24012196
TI  - Arriving at the diagnosis of female sexual dysfunction.
AB  - Female sexual dysfunctions include a group of sexual complaints and disorders
      affecting women of all ages, and stemming from a heterogeneous array of
      etiologies and contributing factors. The classification system for sexual
      dysfunctions in the woman has evolved from a linear categorization of sexual
      desire, arousal, orgasm, and pain disorders to one that is more complex and
      overlapping. Personal distress is a key factor in defining a sexual problem as a
      dysfunction. The recently released Diagnostic and Statistical Manual of Mental
      Disorders, edition 5, collapses former definitions of female sexual disorders and
      moves away from the older linear model of diagnostic categories. Physicians
      should be open to discussing sexual problems with women, and may make use of
      validated questionnaires in the office setting. Evaluation tools available for
      assessing sexual function in the woman are in use in the research setting, as are
      physiological measures of assessment. 

PMID- 24012197
TI  - Differential expression of steroidogenic enzymes according to endometriosis type.
AB  - OBJECTIVE: To evaluate, in peritoneal, ovarian, and rectovaginal endometriotic
      lesions, expression of steroidogenic enzymes involved in the activation and
      inactivation of estrogens: 17beta-hydroxysteroid dehydrogenase type 1 (HSD17B1)
      and 2 (HSD17B2), estrone sulfotransferase (EST), and steroid sulfatase (STS).
      SETTING: Academic gynecology research unit. DESIGN: Retrospective study.
      PATIENT(S): Disease-free (n = 41) patients and patients with endometriosis (n =
      79) were included for quantitative polymerase chain reaction (q-PCR) (15 disease
      free, 33 endometriosis) and immunohistochemistry (26 disease-free, 46
      endometriosis) studies. INTERVENTION(S): Q-PCR and immunohistochemistry. MAIN
      OUTCOME MEASURE(S): Evaluation of mRNA and protein expression. RESULT(S):
      Glandular HSD17B1, HSD17B2, and STS protein expression were demonstrated. HSD17B2
      mRNA values were higher in the secretory phase of the menstrual cycle in the
      endometrium of disease-free women, but not in the eutopic endometrium of patients
      with endometriosis. HSD17B1 mRNA was equally expressed in the various tissues
      investigated, and EST mRNA was expressed at low levels in the different lesion
      types. HSD17B2 mRNA expression was decreased in ovarian and rectovaginal
      endometriosis compared with eutopic endometrium, while STS mRNA was increased in
      rectovaginal lesions compared with ovarian lesions. Ratios between pro- and
      antiestrogenic enzymes (STS/EST and HSD17B1/HSD17B2) were more in favor of
      estrogens in ovarian and rectovaginal endometriosis. CONCLUSION(S): In
      endometriosis development, local activation of estrogens appears to be important.
      STS and HSD17B1 inhibitors may therefore prove useful to treat the disease.

PMID- 24012198
TI  - A tumor necrosis factor-alpha inhibitor reduces the embryotoxic effects of
      endometriotic peritoneal fluid.
AB  - OBJECTIVE: To determine whether a tumor necrosis factor-alpha (TNF-alpha)
      inhibitor can reduce the embryotoxicity of the peritoneal fluid (PF) of women
      with endometriosis. DESIGN: Experimental clinical study. SETTING: University
      hospital. PATIENT(S): Twelve women with chocolate cysts and 12 control women
      without endometriosis. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We
      collected the PF from patients with chocolate cysts (CH-PF) and patients without
      endometriosis (N-PF) during laparoscopic surgery. For the in vitro studies,
      development and apoptosis were evaluated in two-cell stage mouse embryos after
      incubation with CH-PF and N-PF, with or without a TNF-alpha inhibitor. RESULT(S):
      We found that CH-PF significantly decreased the rate of blastocyst development
      and increased the percentage of apoptotic cells in the embryos. Cytokine assays
      showed that the concentrations of several cytokines, including TNF-alpha, were
      higher in embryos incubated with CH-PF than in those incubated with N-PF.
      Furthermore, the treatment of embryos with TNF-alpha retarded development and
      induced apoptosis. Important, adalimumab, a TNF-alpha inhibitor, effectively
      abrogated the embryotoxicity that was induced by CH-PF. CONCLUSION(S): These data
      collectively highlight the crucial role of TNF-alpha in CH-PF-induced
      embryotoxicity and suggest that TNF-alpha inhibitors may be potential therapeutic
      agents for treating endometriosis-induced infertility.

PMID- 24012199
TI  - Effects of chemotherapy and radiotherapy on spermatogenesis in humans.
AB  - Treatment of cancer with chemo- or radiotherapy causes reduction of sperm counts
      often to azoospermic levels that may persist for several years or be permanent.
      The time course of declines in sperm count can be predicted by the sensitivity of
      germ cells, with differentiating spermatogonia being most sensitive, and the
      known kinetics of recovery. Recovery from oligo- or azoospermia is more variable
      and depends on whether there is killing of stem cells and alteration of the
      somatic environment that normally supports differentiation of stem cells. Of the
      cytotoxic therapeutic agents, radiation and most alkylating drugs are the most
      potent at producing long-term azoospermia. Most of the newer biologic targeted
      therapies, except those used to target radioisotopes or toxins to cells, seem to
      have only modest effects, mostly on the endocrine aspects of the male
      reproductive system; however, their effects when used in combination with
      cytotoxic agents have not been well studied. 

PMID- 24012200
TI  - Finasteride use in the male infertility population: effects on semen and hormone
      parameters.
AB  - OBJECTIVE: To determine the degree of improvement in semen parameters after
      finasteride discontinuation. DESIGN: A prospective database of men presenting for
      a fertility evaluation was analyzed for semen and hormone parameters before and
      after discontinuation of finasteride. SETTING: A male infertility specialty
      clinic. PATIENT(S): Men presenting for fertility evaluation from 2008-2012 on
      finasteride. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen and hormone
      parameters before and after discontinuation of finasteride. RESULT(S): At
      presentation, 27 (0.6%) of 4,400 men on finasteride. The mean duration of
      treatment with finasteride was 57.4 months, and mean dose was 1.04 mg/day. There
      was an average 11.6-fold increase in sperm counts after finasteride
      discontinuation. Of the men with severe oligospermia (<5 M/mL), 57% had counts
      increase to >15 M/mL after finasteride cessation. No man had a decrease in sperm
      count. There was no change in hormone parameters, sperm motility, or sperm
      morphology. CONCLUSION(S): Finasteride, even at low doses, may cause reduced
      sperm counts in some men. In this population, counts improved dramatically for
      the majority of men after finasteride discontinuation. The hormone parameters,
      sperm motility, and sperm morphology were unchanged after cessation. Finasteride
      should be discontinued in subfertile men with oligospermia, and used with caution
      in men who desire fertility.

PMID- 24012201
TI  - Potential biomarkers of nonobstructive azoospermia identified in microarray gene
      expression analysis.
AB  - OBJECTIVE: To identify potential biomarkers of azoospermia to determine a
      particular stage of spermatogenetic differentiation. DESIGN: GeneChip Human Gene
      1.0 ST microarray with validation at mRNA and protein levels. SETTING: Basic
      research laboratory. PATIENT(S): Men with various types of nonobstructive
      azoospermia (n = 18) and with normal spermatogenesis (n = 4). INTERVENTION(S):
      Obtaining 31 testicular biopsy samples. MAIN OUTCOME MEASURE(S): Gene expression
      analysis using the Affymetrix Human Gene 1.0 ST microarrays on 14 selected genes
      according to the highest fold change, verified with quantitative polymerase chain
      reaction and on independent set of microarray samples. Western blot and
      immunohistochemistry were additionally performed. RESULT(S): The comparative
      analysis of gene expression profiles in the infertile and control groups resulted
      in the selection of 4,946 differentially expressed genes. AKAP4, UBQLN3, CAPN11,
      GGN, SPACA4, SPATA3, and FAM71F1 were the most significantly down-regulated genes
      in infertile patients. Global analysis also led to identification of up-regulated
      genes-WBSCR28, ADCY10, TMEM225, SPATS1, FSCN3, GTSF1L, and GSG1-in men with late
      maturation arrest. Moreover, the results from quantitative polymerase chain
      reaction and Western blot largely confirmed the microarray data. CONCLUSION(S):
      The set of selected genes can be used to create a molecular diagnostic tool to
      determine the degree of spermatogenic impairment for men with idiopathic
      nonobstructive azoospermia.

PMID- 24012202
TI  - Lens wearers non-compliance - is there an association with lens case
      contamination?
AB  - PURPOSE: This study aims to investigate the association of compliance amongst
      lens wearers and lens case contamination as assessed by the microbial profile of
      lens cases. METHODS: Fifty-two asymptomatic lens wearers filled out
      questionnaires seeking demographic data and several aspects of compliance to lens
      wear. Subsequently, contamination profiles of the inside bottom and rim of their
      lens cases was obtained for bacteria, fungi and Acanthamoeba. The association of
      the self-reported responses in the questionnaire with contamination profile of
      the lens case was then analyzed. RESULTS: Based on compliance criteria, 21% of
      the participants were described as fully compliant lens wearers. Contamination of
      lens case was prevalent in 42% of the cases. Frequent non-compliant behaviours
      reported by study participants included, showering and sleeping with contact
      lenses, and irregular lens case replacement. In comparison to soft contact lens
      wearers prevalence of non-compliance and contamination amongst rigid gas
      permeable (RGP) lens wearers was significantly greater. There was a statistically
      significant correlation between bacterial contamination and current case age.
      CONCLUSION: These results suggest that majority of lens wearers do not fully
      comply with recommendations for lens wear and case care. Crucially, none of the
      fully compliant patients had contaminated lens cases. However it would appear
      that several non-compliant behaviours significantly increase the risks of case
      contamination. These results suggest that greater efforts should be invested with
      lens wearers to ensure enhanced compliance as this is likely to reduce the
      possibility of case contamination.

PMID- 24012204
TI  - Reply from authors re: M. Pilar Laguna. Are we ready for molecular imaging-guided
      surgery? Eur Urol 2014;65:965-6: Molecular imaging-guided surgery: a new frontier
      of urologic surgery?

PMID- 24012203
TI  - Intraoperative continuous norepinephrine infusion combined with restrictive
      deferred hydration significantly reduces the need for blood transfusion in
      patients undergoing open radical cystectomy: results of a prospective randomised
      trial.
AB  - BACKGROUND: Open radical cystectomy (ORC) is associated with substantial blood
      loss and a high incidence of perioperative blood transfusions. Strategies to
      reduce blood loss and blood transfusion are warranted. OBJECTIVE: To determine
      whether continuous norepinephrine administration combined with intraoperative
      restrictive hydration with Ringer's maleate solution can reduce blood loss and
      the need for blood transfusion. DESIGN, SETTING, AND PARTICIPANTS: This was a
      double-blind, randomised, parallel-group, single-centre trial including 166
      consecutive patients undergoing ORC with urinary diversion (UD). Exclusion
      criteria were severe hepatic or renal dysfunction, congestive heart failure, and
      contraindications to epidural analgesia. INTERVENTION: Patients were randomly
      allocated to continuous norepinephrine administration starting with 2 MUg/kg per
      hour combined with 1 ml/kg per hour until the bladder was removed, then to 3
      ml/kg per hour of Ringer's maleate solution (norepinephrine/low-volume group) or
      6 ml/kg per hour of Ringer's maleate solution throughout surgery (control group).
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intraoperative blood loss and the
      percentage of patients requiring blood transfusions perioperatively were
      assessed. Data were analysed using nonparametric statistical models. RESULTS AND
      LIMITATIONS: Total median blood loss was 800 ml (range: 300-1700) in the
      norepinephrine/low-volume group versus 1200 ml (range: 400-2800) in the control
      group (p<0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%)
      required an average of 1.8 U (+/-0.8) of packed red blood cells (PRBCs). In the
      control group, 50 of 83 patients (60%) required an average of 2.9 U (+/-2.1) of
      PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI],
      0.38-0.77; p=0.0006). The absolute reduction in transfusion rate throughout
      hospitalisation was 28% (95% CI, 12-45). In this study, surgery was performed by
      three high-volume surgeons using a standardised technique, so whether these
      significant results are reproducible in other centres needs to be shown.
      CONCLUSIONS: Continuous norepinephrine administration combined with restrictive
      hydration significantly reduces intraoperative blood loss, the rate of blood
      transfusions, and the number of PRBC units required per patient undergoing ORC
      with UD.

PMID- 24012205
TI  - Salvage radical prostatectomy in nonmetastatic castration-resistant prostate
      cancer patients who received previous radiotherapy: a feasibility study.

PMID- 24012206
TI  - Should antibiotics be given prior to outpatient cystoscopy? A plea to urologists
      to practice antibiotic stewardship.
AB  - BACKGROUND: Antimicrobial resistance is a major health problem, caused primarily
      by overuse of antibiotics in clinical situations in which they are not necessary.
      Practice guidelines recommend that antibiotics be given before outpatient
      cystoscopy to prevent symptomatic urinary tract infection (UTI). OBJECTIVE: To
      determine the frequency of febrile UTI after outpatient flexible cystoscopy in
      antibiotic-naive bladder tumor patients. DESIGN, SETTING, AND PARTICIPANTS: A
      total of 2010 consecutive outpatients with bladder tumors were entered into a
      prospective registry study. All patients underwent cystoscopy after they
      submitted a voided urine sample for culture. Significant bacteriuria was defined
      as >10(4) colony-forming units per milliliter with a single organism. Patients
      were stratified for known risk factors for UTI. INTERVENTION: Patients underwent
      flexible cystoscopy and received no antibiotics immediately before or after
      cystoscopy. They were followed for 30 d for onset of febrile UTI. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: The end point was incidence of febrile UTI
      within 30 d of cystoscopy. Febrile UTI was defined as temperature >38 degrees C
      and dysuria, or having received antibiotics from an outside physician for urinary
      symptoms. RESULTS AND LIMITATIONS: Of the 2010 patient cystoscopies, 489 (24%)
      had asymptomatic bacteriuria, and 1521 (76%) had sterile urine. Thirty-nine
      patients (1.9%) developed febrile UTI <=30 d after cystoscopy-4.5% in colonized
      patients and 1.1% in uninfected patients (p=0.02). All UTIs resolved in <=12-24h
      with oral antibiotics. None of the patients was admitted for bacterial sepsis.
      Limitations of the study are that it is a single-surgeon experience in one
      institution, and results may not apply to other patient populations. CONCLUSIONS:
      Antibacterial therapy before outpatient flexible cystoscopy does not appear
      necessary in bladder tumor patients who have no clinical signs or symptoms of
      acute UTI, including asymptomatic bacteriuria. Antibiotic stewardship is the
      responsibility of all urologists.

PMID- 24012207
TI  - Comparative actions of omega-3 fatty acids on in-vitro lipid droplet formation.
AB  - Storage of fat into lipid droplets (LDs) is the key step in adipogenesis.
      Previously the omega-3 polyunsaturated fatty acid (n-3PUFA) eicosapentaenoic acid
      (EPA; C20:5n-3) has been shown to suppress LD formation, yet the actions of other
      n-3PUFA is unknown. Here, we examined the impact of the three major long chain n
      3PUFA; EPA, docosapentaenoic acid (DPA; C22:5n-3) and docosahexaenoic acid (DHA;
      C22:6n-3) on LD formation in 3T3-L1 adipocytes. Cells were supplemented with
      100uM fatty acid during differentiation. All n-3PUFA significantly reduced LD
      formation and the metabolic disorder marker, SCD1, in comparison to stearic acid
      (STA; C18:0). This action was more potent for DHA than either EPA or DPA.
      Furthermore, DHA significantly increased lipolysis and ATGL gene and protein
      expression but reduced the gene expression of three proteins related to LD
      formation (Perilipin A, Caveolin-1 and Cidea), compared with other n-3PUFA. Thus,
      DHA, above EPA and DPA, markedly suppressed fat storage in LDs in in-vitro
      adipocytes. 

PMID- 24012208
TI  - Multislice computed tomography with colon water distension (MSCT-c) in the study
      of intestinal and ureteral endometriosis.
AB  - This study evaluates retrospectively the accuracy and reproducibility of
      multislice computed tomography with colon water distension (MSCT-c) in diagnosing
      bowel (BE) and ureteral (UE) endometriosis. Sixty-four patients underwent MSCT-c
      and videolaparoscopic surgery. Two radiologists reviewed MSCT-c examinations:
      sensitivity and specificity were calculated, considering histological exam as
      reference standard. In the BE cases, the degree of bowel wall infiltration was
      also assessed. Sensitivity and specificity for both readers were 100% and 97.6%
      for BE and 72.2% and 100% for UE; the interobserver agreement was excellent. The
      degree of bowel wall involvement was correctly defined in 90.9% of cases. MSCT-c
      is an accurate and reproducible technique but-considering the age of the patients
      delivers a nonnegligible radiation dose.

PMID- 24012209
TI  - High-content cytometry and transcriptomic biomarker profiling of human B-cell
      activation.
AB  - BACKGROUND: Primary antibody deficiencies represent the most prevalent, although
      very heterogeneous, group of inborn immunodeficiencies, with a puzzling
      complexity of cellular and molecular processes involved in disease pathogenesis.
      OBJECTIVE: We aimed to study in detail the kinetics of CD40 ligand/IL-21-induced
      B-cell differentiation to define new biomarker sets for further research into
      primary antibody deficiencies. METHODS: We applied high-content screening methods
      to monitor B-cell activation on the cellular (chip cytometry) and transcriptomic
      (RNA microarray) levels. RESULTS: The complete activation process, including
      stepwise changes in protein and RNA expression patterns, entry into the cell
      cycle, proliferation and expression of activation-induced cytidine deaminase
      (AID), DNA repair enzymes, and post-class-switch expression of IgA and IgG, was
      successfully monitored during in vitro differentiation. We identified a number of
      unknown pathways engaged during B-cell activation, such as CXCL9/CXCL10 secretion
      by B cells. Finally, we evaluated a deduced set of biomarkers on a group of 18
      patients with putative or proved intrinsic B-cell defects recruited from the
      European Society for Immunodeficiencies database and successfully predicted 2 AID
      defects and 1 DNA repair defect. Complete absence of class-switched B cells was a
      sensitive predictor of AID deficiency and should be further evaluated as a
      diagnostic biomarker. CONCLUSION: The biomarkers found in this study could be
      used to further study the complex process of B-cell activation and to understand
      conditions that lead to the development of primary antibody deficiencies.

PMID- 24012210
TI  - Uncorrected nitric oxide levels in mild asthmatics produce flawed interpretation.

PMID- 24012211
TI  - Usefulness of alveolar nitric oxide measurement in asthma: still debated.

PMID- 24012214
TI  - Lymphangiomatous macroglossia associated with extensive cervicomediastinal cystic
      hygromas.
AB  - Children with lymphangiomatous macroglossia often have difficulty eating and
      talking, and their airways may be compromised because of bleeding and infection,
      especially when extensive cervicomediastinal cystic hygromas are present. We
      report a case of lymphangiomatous macroglossia associated with extensive cystic
      hygromas in the cervicomediastinal region. The 3-year-old girl was treated with
      anterior wedge reduction of the tongue, needle aspiration of the
      cervicomediastinal cystic hygromas, and systemic steroids and antibiotics. The
      extensive cystic cervicomediastinal hygromas spontaneously regressed, and further
      surgery was not needed until 4 years later. Surprisingly, subtotal or partial
      lymphatic malformation removal improved the complicated lymphatic malformation. 

PMID- 24012215
TI  - Standardized evaluation methodology and reference database for evaluating IVUS
      image segmentation.
AB  - This paper describes an evaluation framework that allows a standardized and
      quantitative comparison of IVUS lumen and media segmentation algorithms. This
      framework has been introduced at the MICCAI 2011 Computing and Visualization for
      (Intra)Vascular Imaging (CVII) workshop, comparing the results of eight teams
      that participated. We describe the available data-base comprising of multi
      center, multi-vendor and multi-frequency IVUS datasets, their acquisition, the
      creation of the reference standard and the evaluation measures. The approaches
      address segmentation of the lumen, the media, or both borders; semi- or fully
      automatic operation; and 2-D vs. 3-D methodology. Three performance measures for
      quantitative analysis have been proposed. The results of the evaluation indicate
      that segmentation of the vessel lumen and media is possible with an accuracy that
      is comparable to manual annotation when semi-automatic methods are used, as well
      as encouraging results can be obtained also in case of fully-automatic
      segmentation. The analysis performed in this paper also highlights the challenges
      in IVUS segmentation that remains to be solved. 

PMID- 24012216
TI  - Analysis of gene expression profiles in tympanic membrane following perforation
      using PCR Array in rats--preliminary investigation.
AB  - OBJECTIVES: The goal of this work was to identify genes, known to be involved in
      the skin wound healing, that express differentially in the healthy and injured
      tympanic membrane (TM), and designate the molecules potentially beneficial for
      treatment of TM perforation. The molecular mechanisms controlling the course of
      TM regeneration are far from being elucidated. METHODS: Twenty rats had their
      tympanic membranes perforated, while four served as a control. Animals were
      sacrificed on either days 1, 2, 3, 5 and 10 post injury, and TMs were immediately
      dissected and frozen in liquid nitrogen. Total TM RNA was isolated and reversely
      transcribed. qPCR was performed using Rat Wound Healing RT(2) Profiler PCR Array
      (QIAGEN) containing primers for 84 genes. RESULTS: Statistically significant
      changes in the expression of 42 genes were found in various stages of TM healing.
      The increased expression of genes taking part in the inflammatory reaction
      (interleukin 6, granulocyte and macrophage chemotactic proteins) was observed
      from day 2. The expression of several genes of extracellular matrix components
      and their remodeling enzymes was also changed. Among growth factor genes: Vegfa,
      Igf1 and Hbegf showed increased expression at the beginning of the healing
      process, while Hgf expression was highest on day 3. CONCLUSIONS: Several changes
      in the expression of genes involved in remodeling of extracellular matrix point
      to important role of connective tissue in TM healing. The molecules accelerating
      this process, like HbEGF and HGF, seem to be good candidates for further
      evaluation of their possible use in clinical treatment.

PMID- 24012217
TI  - Letter to the editor regarding "systematic review of intralesional cidofovir
      dosing regimens in the treatment of recurrent respiratory papillomatosis".

PMID- 24012218
TI  - Consumer acoustic reflectometry: accuracy in diagnosis of otitis media with
      effusion in children.
AB  - OBJECTIVE: Acoustic reflectometry is a technique based on a sonar that enables
      the diagnosis of middle ear effusion. We aimed to evaluate the accuracy and
      diagnostic value of consumer type acoustic reflectometry device for determining
      middle ear effusion in children. METHODS: Acoustic reflectometry and
      tympanometries of 84 children, from 3 to 14 years of age, were done the day
      before they underwent adenoidectomy/adenotonsillectomy and myringotomy +/-
      ventilation tube insertion under general anesthesia in the operating room with
      diagnosis of middle ear effusion. Their test results and the results of
      myringotomies, which is the golden standard technique in determination of otitis
      media with effusion, were compared. Specificity, sensitivity, positive and
      negative predictive values of both instruments in detecting middle ear fluid were
      determined. RESULTS: Otitis media with effusion was detected in 106 ears (63.1%)
      during myringotomy. The sensitivity and specificities of acoustic reflectometry
      were found to be 83.33% and 68.18%, and tympanometry were 84.48% and 84.62%,
      respectively. The positive predictive value was 75.12% for acoustic reflectometry
      and 88.56% for tympanometry, and negative predictive values of acoustic
      reflectometry and tympanometry were 87.66% and 89.2%, respectively. The
      sensitivity of the AR was comparable to tympanometry (p > 0.01), however the
      specificity, PPV and NPV of AR were lower than tympanometry (p < 0.001).
      CONCLUSIONS: Consumer type acoustic reflectometry is highly sensitive, objective
      and easy to perform technique for detecting otitis media with effusion, and it
      may help us to diagnose otitis media with effusion in early stages if used by
      family practitioners or parents.

PMID- 24012219
TI  - Microarray analysis of gene expression alteration in human middle ear epithelial
      cells induced by micro particle.
AB  - OBJECTIVES: The primary aim of this study is to reveal the effect of particulate
      matter (PM) on the human middle ear epithelial cell (HMEEC). METHODS: The HMEEC
      was treated with PM (300 MUg/ml) for 24 h. Total RNA was extracted and used for
      microarray analysis. Molecular pathways among differentially expressed genes were
      further analyzed by using Pathway Studio 9.0 software. For selected genes, the
      changes in gene expression were confirmed by real-time PCR. RESULTS: A total of
      611 genes were regulated by PM. Among them, 366 genes were up-regulated, whereas
      245 genes were down-regulated. Up-regulated genes were mainly involved in
      cellular processes, including reactive oxygen species generation, cell
      proliferation, apoptosis, cell differentiation, inflammatory response and immune
      response. Down-regulated genes affected several cellular processes, including
      cell differentiation, cell cycle, proliferation, apoptosis and cell migration. A
      total of 21 genes were discovered as crucial components in potential signaling
      networks containing 2-fold up regulated genes. Four genes, VEGFA, IL1B, CSF2 and
      HMOX1 were revealed as key mediator genes among the up-regulated genes. A total
      of 25 genes were revealed as key modulators in the signaling pathway associated
      with 2-fold down regulated genes. Four genes, including IGF1R, TIMP1, IL6 and
      FN1, were identified as the main modulator genes. CONCLUSIONS: We identified the
      differentially expressed genes in PM-treated HMEEC, whose expression profile may
      provide a useful clue for the understanding of environmental pathophysiology of
      otitis media. Our work indicates that air pollution, like PM, plays an important
      role in the pathogenesis of otitis media.

PMID- 24012220
TI  - The universal newborn hearing screening program of Taipei City.
AB  - OBJECTIVES: To establish a hearing screening program with high coverage, low
      referral rate, high follow-up rate, and early intervention in Taipei City.
      METHODS: From September 2009 to December 2010, 85% delivery units in Taipei City,
      which includes 20 hospitals and 14 obstetrics clinics, were recruited into the
      screening program in two stages. A total of 15,930 babies were born in these
      participating hospitals and clinics during the program period. Among these
      neonates, 15,790 underwent hearing screening test with automatic auditory
      brainstem response (AABR). The screening was free of charge to the parents. The
      hearing screening examination was performed 24-36 h after birth. The same test
      was repeated between 36 and 60 h of age if the baby failed the first hearing
      test. The neonate was referred to the diagnostic hospitals for further
      investigations if he failed the second test. RESULTS: The screening coverage rate
      was 99.1% (15,790/15,930). The incidence of bilateral moderate to severe and
      unilateral hearing loss was 1.4 per 1000 (22/15,790) and 1.5 per 1000
      (24/15,790), respectively. Four percent (626/15,790) of newborns failed to pass
      the initial screening test and 1.0% of newborns failed to pass the second
      screening test. Therefore, 1.0% newborns were referred for diagnostic
      assessments. The follow-up rate was 94.4% (151/160). Sixty-four percent (14/22)
      of babies with bilateral hearing loss completed the full diagnostic hearing tests
      within 3 months of birth. CONCLUSIONS: The universal newborn hearing screening
      program is an adequate program for Taipei City with high coverage, low referral
      rate, and good follow-up rate. Screening fees covered by third parties, two-stage
      screening steps with AABR strategy, and the stringent monitoring system proved to
      be effective. LEVEL OF EVIDENCE: 2b, individual cohort study.

PMID- 24012221
TI  - Efficacy of HGF carried by ultrasound microbubble-cationic nano-liposomes complex
      for treating hepatic fibrosis in a bile duct ligation rat model, and its
      relationship with the diffusion-weighted MRI parameters.
AB  - Hepatic fibrosis is a major consequence of liver aggression. Finding novel ways
      for counteracting this damaging process, and for evaluating fibrosis with a non
      invasive imaging approach, represent important therapeutic and diagnostic
      challenges. Hepatocyte growth factor (HGF) is an anti-fibrosis cell growth factor
      that induces apoptosis in activated hepatic stellate cells, reduces excessive
      collagen deposition, and stimulates hepatocyte regeneration. Thus, using HGF in
      gene therapy against liver fibrosis is an attractive approach. The aims of the
      present study were: (i) to explore the efficacy of treating liver fibrosis using
      HGF expression vector carried by a novel ultrasound microbubble delivery system;
      (ii) to explore the diagnostic interest of diffusion-weighted MRI (DWI-MRI) in
      evaluating liver fibrosis. We established a rat model of hepatic fibrosis. The
      rats were administered HGF linked to novel ultrasound micro-bubbles. Progression
      of hepatic fibrosis was evaluated by histopathology, hydroxyproline content, and
      DWI-MRI to determine the apparent diffusion coefficient (ADC). Our targeted gene
      therapy produced a significant anti-fibrosis effect, as shown by liver histology
      and significant reduction of hydroxyproline content. Moreover, using DWI-MRI, the
      b value (diffusion gradient factor) was equal to 300s/mm(2), and the ADC values
      significantly decreased as the severity of hepatic fibrosis increased. Using this
      methodology, F0-F2 could be distinguished from F3 and F4 (P<0.01). This is the
      first in vivo report of using an ultrasound microbubble-cationic nano-liposome
      complex for gene delivery. The data indicate that, this approach is efficient to
      counteract the fibrosis process. DWI-MRI appears a promising imaging technique
      for evaluating liver fibrosis. 

PMID- 24012222
TI  - Pediatric asthma evaluation: what's to be considered?
AB  - The increasing evidence that asthma begins very early in childhood leads the need
      for having outcome's measures able to identify the early damage and its evolution
      both for research than for clinical purposes. The current available methods are
      clinical questionnaires, pulmonary function tests, airway reactivity tests and
      direct or indirect inflammation markers' measures. Among the first, ISAAC
      questionnaire, for epidemiological purpose, Asthma Control Test, for clinical
      monitoring and Health Related Quality of Life questionnaire are the most used.
      There are many pulmonary function tests that may be used in all age for
      functional evaluation, but airway responsiveness measures may be commonly
      performed only in school age children. As regards respiratory inflammation
      measures the only currently useful is the exhaled nitric oxide evaluation. The
      complexity of the pathogenic mechanisms, molecular, cellular and inflammatory
      that realize the asthmatic syndrome and the effects of the disease on respiratory
      function, on the activity of the child, on the quality of life of the family and
      on the economic costs to society show that there is no a single outcome measure
      that can evaluate all these effects simultaneously. 

PMID- 24012223
TI  - Extra-torque of human tibialis anterior during electrical stimulation with
      linearly varying frequency and amplitude trains.
AB  - This work aimed to characterise the whole human muscle input/output law during
      electrical stimulation with triangular varying frequency and amplitude trains
      through combined analysis of torque, mechanomyogram (MMG) and electromyogram
      (EMG). The tibialis anterior (TA) of ten subjects (age 23-35 years) was
      investigated during static contraction obtained through neuromuscular electrical
      stimulation. After potentiation, TA underwent two 15s stimulation patterns: (a)
      frequency triangle (FT): 2 > 35 > 2 Hz at Vmax (amplitude providing full motor
      unit recruitment); (b) amplitude triangle (AT): Vmin > Vmax > Vmin (Vmin
      providing TA least mechanical response) at 35 Hz. 2 > 35 Hz or Vmin > Vmax as
      well as 35 > 2 Hz or Vmax > Vmin were defined as up-going ramp (UGR) and down
      going ramp (DGR), respectively. TA torque, MMG and EMG were detected by a load
      cell, an optical laser distance sensor and a probe with two silver bar
      electrodes, respectively. For both FT and AT, only the two mechanical signals
      resulted always larger in DGR than in UGR, during AT extra-torque and extra-MMG
      were present even in the first 1/3 of the amplitude range where EMG data
      presented no significant differences between DGR and UGR. Our data suggest that
      extra-torque and extra-displacement are evident for both FT and AT, being mainly
      attributed to an intrinsic muscle property.

PMID- 24012224
TI  - Cellular morphometry in late-life depression: a review of postmortem studies.
AB  - The impact of major depression in late life is considerable and set to intensify
      with a worldwide shift in demographic profile toward an elderly population.
      Although the precise neurobiological mechanisms are not fully understood, a
      significant body of clinical, epidemiological, and imaging data have suggested
      divergent pathophysiological pathways underlie depression in late life, when
      compared with younger patients. Neuroimaging studies have demonstrated
      significant increases in white matter hyperintensities in late-life depression in
      several key areas involved in affective circuitry. Postmortem cellular
      morphometry studies have played a vital role in the identification of discrete
      changes in the brain microstructure in depression. This review draws together
      such postmortem studies, which have utilized tissue from younger/mixed age and
      late-life depressed patients. These findings have suggested varying neuronal and
      glial cell pathology in depression between different age cohorts. This age
      related disparity may suggest different pathophysiological basis for depression,
      with vascular factors playing a potentially greater role in late life. 

PMID- 24012225
TI  - Comparison of anxiety as reported by older people with intellectual disabilities
      and by older people with normal intelligence.
AB  - OBJECTIVES: Older people with intellectual disabilities (ID) may experience more
      and different symptoms of anxiety than older people with normal intelligence.
      STUDY QUESTIONS: (1) Is the reported severity of anxiety in this group similar to
      that in the general older population; (2) Are specific anxiety symptoms reported
      as frequently by both groups? DESIGN: Cross-sectional. SETTING: Formal Dutch
      intellectual disability services and Dutch population-based study. PARTICIPANTS:
      One hundred fifty-four participants of the Healthy Ageing and Intellectual
      Disability study with mild or moderate ID (IQ <70), aged 55-85 years, and 2,917
      participants of the Longitudinal Aging Study Amsterdam with normal intelligence,
      aged 55-85 years. MEASUREMENTS: The general anxiety subscale of the Hospital
      Anxiety and Depression Scale. RESULTS: Mean (standard deviation) Hospital Anxiety
      and Depression Scale total score of subjects with ID was significantly higher
      than that of subjects with normal intelligence (3.53 [3.03]) versus 2.53 [3.30];
      p <0.01), whereas the percentage of scores above cutoff in both groups was
      similar. Four of 7 items were more often reported as present by subjects with ID:
      "tense or wound up feelings," "frightened feelings," "worrying thoughts," and
      "sudden feelings of panic." CONCLUSIONS: Older people with ID report more
      symptoms of anxiety than older people with normal intelligence. Tense feelings
      and worrying especially need more attention, because more than one-half of all
      older people with ID reported such symptoms.

PMID- 24012226
TI  - Prevalence and predictors of burden in caregivers of people with dementia.
AB  - OBJECTIVE: To examine prevalence and predictors of burden in caregivers of people
      with dementia attending memory clinics. METHODS: This Prospective cohort study
      conducted at nine memory clinics in Australia rated 732 outpatient attendees and
      their primary caregivers at baseline and at 3, 6, 12, 24, and 36 months. Ratings
      were based on the following: dementia diagnosis according to the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, Mini-Mental State Exam,
      Alzheimer's Disease Assessment Scale-Cognitive, Functional Autonomy Measurement
      System, Neuropsychiatric Inventory, use of psychotropic and antidepressant
      medications, patient and caregiver resource use, and the Zarit Caregiver Burden
      Interview (ZBI). RESULTS: Half the caregivers had significantly high levels of
      burden, rising to 57.7% at 12 months; with moderate to severe burden rates,
      rising from 14.7% at baseline to 22.8% at 12 months; and mean ZBI levels rising
      from 22.9 at baseline to 25.5 at 6 months and 27.7 at 12 months. Caregiver
      predictors of 6- and 12-month burden were their neuroticism and baseline ZBI
      score. Patient predictors were their level of behavioral symptoms, use of
      antipsychotics and antidepressants, and more rapid functional decline. Other
      predictors (female caregiver, level of cognition and function, diagnosis of
      frontotemporal dementia) were not significant in regression analyses. CONCLUSION:
      Caregivers of people with dementia have high and persistent rates of burden.
      Identification of caregivers likely to have high levels of burden at 12 months
      may allow more accurate targeting of interventions.

PMID- 24012227
TI  - Time does not heal all wounds: older adults who experienced childhood adversities
      have higher odds of mood, anxiety, and personality disorders.
AB  - OBJECTIVE: We aimed to examine the prevalence of several types of childhood
      adversity across adult cohorts, whether age moderates the effect of childhood
      adversity on mental health, the relationship between childhood adversity and
      psychopathology among older adults, the dose-response relationship between number
      of types of childhood adversities and mental disorders in later life, and whether
      lifetime mental health treatment reduces the odds of psychopathology among older
      survivors of childhood adversity. METHODS: In a population-based, cross-sectional
      study on a nationally representative U.S. sample, we studied 34,653 community
      dwelling Americans 20 years and older, including 7,080 adults 65 years and older
      from Wave 2 of the National Epidemiologic Survey on Alcohol and Related
      Conditions. Trained lay interviewers assessed past-year mood and anxiety
      disorders and lifetime personality disorders. Participants self-reported
      childhood adversity based on questions from the Adverse Childhood Experiences
      Study. RESULTS: Childhood adversity was prevalent across five age cohorts. In our
      adjusted models, age did not moderate the effect of childhood adversity on mental
      disorders. Older adults who experienced childhood adversity had higher odds of
      having mood (odds ratio: 1.73; 95% confidence interval: 1.32-2.28), anxiety (odds
      ratio: 1.48; 95% confidence interval: 1.20-1.83), and personality disorders (odds
      ratio: 2.11; 95% confidence interval: 1.75-2.54) after adjusting for covariates.
      An increasing number of types of childhood adversities was associated with higher
      odds of personality disorders and somewhat higher odds of anxiety disorders.
      Treatment-seeking was associated with a reduced likelihood of anxiety and,
      especially, mood disorders in older adult childhood adversity survivors.
      CONCLUSION: These results emphasize the importance of preventing childhood
      adversity and intervening once it occurs to avoid the negative mental health
      effects that can last into old age.

PMID- 24012228
TI  - Predictors of suicidal ideation in older people: a decision tree analysis.
AB  - OBJECTIVES: Suicide among older adults is a major public health issue worldwide.
      Although studies have identified psychological, physical, and social contributors
      to suicidal thoughts in older adults, few have explored the specific interactions
      between these factors. This article used a novel statistical approach to explore
      predictors of suicidal ideation in a community-based sample of older adults.
      DESIGN: Prospective cohort study. PARTICIPANTS AND SETTING: Participants aged 55
      85 years were randomly selected from the Hunter Region, a large regional center
      in New South Wales, Australia. MEASUREMENTS: Baseline psychological, physical,
      and social factors, including psychological distress, physical functioning, and
      social support, were used to predict suicidal ideation at the 5-year follow-up.
      Classification and regression tree modeling was used to determine specific risk
      profiles for participants depending on their individual well-being in each of
      these key areas. RESULTS: Psychological distress was the strongest predictor,
      with 25% of people with high distress reporting suicidal ideation. Within high
      psychological distress, lower physical functioning significantly increased the
      likelihood of suicidal ideation, with high distress and low functioning being
      associated with ideation in 50% of cases. A substantial subgroup reported
      suicidal ideation in the absence of psychological distress; dissatisfaction with
      social support was the most important predictor among this group. The performance
      of the model was high (area under the curve: 0.81). CONCLUSIONS: Decision tree
      modeling enabled individualized "risk" profiles for suicidal ideation to be
      determined. Although psychological factors are important for predicting suicidal
      ideation, both physical and social factors significantly improved the predictive
      ability of the model. Assessing these factors may enhance identification of older
      people at risk of suicidal ideation.

PMID- 24012229
TI  - Monitoring in the 21st century: from Hiob to Hermes?

PMID- 24012230
TI  - Monitoring volume and fluid responsiveness: from static to dynamic indicators.
AB  - Fluid therapy represents, most of the time, the first-line treatment of
      circulatory failure in critically ill patients. However, after initial
      resuscitation, fluid administration can be deleterious in patients with sepsis
      and/or acute respiratory distress syndrome. In this context, several tests have
      been developed to predict fluid responsiveness and fluid unresponsiveness to
      identify patients who can be eligible for fluid therapy (fluid respondents) and
      those who cannot benefit from volume expansion (fluid non-respondents) and in
      whom fluid loading can even be deleterious. For this purpose, 'static' markers of
      cardiac preload have been used for many years. However, a large number of studies
      clearly showed that neither pressure nor volume markers of cardiac preload could
      predict fluid responsiveness. This is the reason why a 'dynamic approach' has
      been developed to assess preload responsiveness. The respiratory variation of
      arterial pulse pressure and of other surrogates of stroke volume has been used
      first for this purpose and has received a large amount of evidence. However, such
      indices suffer from several limitations. In such instances, alternative methods
      such as passive leg raising, end-expiratory occlusion test or 'mini' fluid
      challenge have been developed. 

PMID- 24012231
TI  - Monitoring cardiac function: echocardiography, pulse contour analysis and beyond.
AB  - Haemodynamic monitoring has developed considerably over the last decades,
      nowadays comprising a wide spectrum of different technologies ranging from
      invasive to completely non-invasive techniques. At present, the evidence to
      continuously measure and optimise stroke volume, that is, cardiac output, in
      order to prevent occult hypoperfusion in the perioperative setting and
      consequently to improve patients' outcome is substantial. Surprisingly, there is
      a striking discrepancy between the developments in advanced haemodynamic
      monitoring combined with evidence-based knowledge on the one hand and daily
      clinical routine on the other hand. Recent trials have shown that perioperative
      mortality is higher than anticipated, emphasising the need for the speciality of
      anaesthesiology to face the problem and to translate proven concepts into
      clinical routine to improve patients' outcome. One basic principle of these
      concepts is to monitor and to optimise cardiac function by means of advanced
      haemodynamic monitoring, using echocardiography, pulse contour analysis and
      beyond. 

PMID- 24012232
TI  - The oxygen supply-demand balance: a monitoring challenge.
AB  - The principal task of acute critical care is to avoid or correct oxygen debt by
      increasing oxygen delivery (DO2) and/or decreasing oxygen consumption (VO2). The
      most commonly used methods to assess the relationship of adequate delivery and
      consumption are mixed venous oxygen saturation and its surrogate, central venous
      oxygen saturation (ScvO2). The purpose of this article is to review the values
      and limitations of the two parameters and evaluate the clinical use of ScvO2 in
      certain clinical scenarios, such as anaemia and transfusion, hypovolaemia, major
      surgery, septic shock, and in difficult-to-wean patients. 

PMID- 24012233
TI  - Monitoring respiration: what the clinician needs to know.
AB  - A recent large prospective cohort study showed an unexpectedly high in-hospital
      mortality after major non-cardiac surgery in Europe, as well as a high incidence
      of postoperative pulmonary complications. The direct effect of postoperative
      respiratory complications on mortality is still under investigation, for
      intensive care unit (ICU) and in the perioperative period. Although respiratory
      monitoring has not been actually proven to affect in-hospital mortality, it plays
      an important role in patient care, leading to appropriate setting of ventilatory
      support as well as risk stratification. The aim of this article is to provide an
      overview of various respiratory monitoring techniques including the role of
      conventional and most recent methods in the perioperative period and in
      critically ill patients. The most recent techniques proposed for bedside
      respiratory monitoring, including lung imaging, are presented and discussed,
      comparing them to those actually considered as gold standards. 

PMID- 24012234
TI  - Brain monitoring revisited: what is it all about?
AB  - To easily measure the depth of anaesthesia during routine surgical procedures has
      always been a goal in anaesthesiology. For decades, scientists have been
      developing indices to describe and evaluate the depth of anaesthesia.
      Historically, mean alveolar gas concentration (MAC) values for volatile
      anaesthetics have been used to target a predefined level of anaesthesia. MAC
      values were however not established to differentiate between the hypnotic and
      analgesic components of anaesthesia. Indices were therefore developed that
      measure the effect of hypnotics predominantly on the brain (in contrast to an
      effect on the spinal cord) with the vision to be able to measure the transition
      from consciousness to unconsciousness. Although monitors measuring the depth of
      anaesthesia are still not capable of measuring the transition from consciousness
      to unconsciousness, brain monitoring has proved to help clinicians control the
      depth of anaesthesia. Clinical trials have shown that the use of brain-monitoring
      devices can lead to a reduction of intraoperative drug consumption, reduced
      incidence of postoperative nausea and vomiting, facilitate recovery from
      anaesthesia compared to routine care and can also lead to a reduction of
      intraoperative awareness. However a study demonstrating both a reduced
      intraoperative drug consumption and at the same time a reduction of
      intraoperative awareness due to the use of brain-monitoring devices has not been
      published yet. 

PMID- 24012235
TI  - Monitoring the nociception-anti-nociception balance.
AB  - At present, short-acting drugs are used in order to achieve the three components
      of anaesthesia, that is, analgesia, hypnosis and immobility. Assessment of the
      'analgesia' component in daily clinical routine is, in contrast to the other
      components, still based on very unspecific clinical 'end' points such as
      movement, tearing, tachycardia or hypertension. Individually tailored analgesia,
      however, should enable to maintain an individual nociceptive-anti-nociceptive
      balance and better avoid these unwanted responses to surgical stimulation. During
      the last decade, a variety of monitoring systems were developed in order to
      assess the nociceptive balance. These are, among others, based on the frontal
      electroencephalography (EEG) and electromyography (EMG) response, evaluation of
      the autonomic state and autonomic reactions, spinal reflex pathways and
      calculated drug concentrations. The present review gives an overview on the topic
      of 'analgesia' monitoring, the available monitoring systems and their clinical
      evaluation. Most of the systems allow a rapid detection of the nociceptive input;
      nonetheless, the prediction of an autonomic or somatic response has still to be
      improved. Several studies reported fewer unwanted events, reduced opioid
      consumption and shorter emergence from anaesthesia, when opioid administration
      was based upon monitoring of the nociceptive-anti-nociceptive balance. However,
      research on the mechanisms of pain processing and for better tools to assess the
      'analgesia' component has to continue in order to improve our daily practice. 

PMID- 24012236
TI  - Intra-abdominal hypertension: definitions, monitoring, interpretation and
      management.
AB  - This review will describe the definitions on intra-abdominal hypertension (IAH)
      and abdominal compartment syndrome (ACS). In order to understand these
      definitions the reader must be aware of the interactions between intra-abdominal
      pressure (IAP) and intra-abdominal volume (IAV), explaining why dramatic IAP
      increases can be observed in some patients related to anthropomorphic
      measurements, body positioning, use of positive pressure ventilation, or
      relatively small accumulations of fluid or blood. The adverse effects related to
      increased IAP have been named IAH for moderate cases and ACS for advanced cases.
      In order to improve clinical communication as well as evaluation of the
      scientific literature, the World Society for the Abdominal Compartment Syndrome
      (WSACS) has published its first guidelines and definitions in 2006. The
      definitions and guidelines have recently been revised according to evidence based
      medicine and the Grading of Recommendations Assessment, Development and
      Evaluation (GRADE) methodology. This review will be based on the revised
      guidelines. The standard method to measure IAP is via the bladder and as
      experience with IAP measurement has evolved considerably, a number of tips and
      potential pitfalls are listed. 

PMID- 24012237
TI  - The kidney in critical illness: how to monitor a pivotal organ system.
AB  - Acute kidney injury is an important complication in patients undergoing major and
      especially cardiac surgery and in the critically ill. Within the last years,
      several new modalities have been developed for monitoring of renal function that
      may be used for early detection of patients developing renal dysfunction as well
      as to monitor the effects of treatments on this pivotal organ. The present
      manuscript aims to give a critical overview about recent developments in the
      field. 

PMID- 24012238
TI  - Monitoring infection: from blood culture to polymerase chain reaction (PCR).
AB  - In patients with sepsis, diagnosis of blood stream infection (BSI) is a key
      concern to the therapist. Direct verification of pathogens in the blood stream
      executed by blood cultures (BC) still is regarded as the gold standard up to
      date. The quickest possible initiation of an appropriate antimicrobial therapy is
      a cornerstone of an effective therapy. Moreover, in this view BC can also serve
      to identify antimicrobial agents to target the pathogen. However, when employing
      BC the time needed until microbiological results are available ranges from 24 up
      to 72 h. Moreover, infections caused by multiple pathogens often remain
      undetected and concurrent antibiotic therapy may lower the overall sensitivity.
      Alternative pathogen characterization can be performed by polymerase chain
      reaction (PCR) based amplification methods. Results using PCR can be obtained
      within 6-8 h. Therefore, the time delay until an appropriate therapy can be
      reduced enormously. Moreover, these methods have the potential to enhance the
      sensitivity in the diagnosis of blood stream infections. Therefore, PCR based
      methods might be a valuable adjunct to present procedures of diagnosing
      bacteraemia. 

PMID- 24012240
TI  - Bronchioloalveolar carcinoma: time for a new term.

PMID- 24012239
TI  - Limnobacter spp. as newly detected phenol-degraders among Baltic Sea surface
      water bacteria characterised by comparative analysis of catabolic genes.
AB  - A set of phenol-degrading strains of a collection of bacteria isolated from
      Baltic Sea surface water was screened for the presence of two key catabolic genes
      coding for phenol hydroxylases and catechol 2,3-dioxygenases. The multicomponent
      phenol hydroxylase (LmPH) gene was detected in 70 out of 92 strains studied, and
      41 strains among these LmPH(+) phenol-degraders were found to exhibit catechol
      2,3-dioxygenase (C23O) activity. Comparative phylogenetic analyses of LmPH and
      C23O sequences from 56 representative strains were performed. The studied strains
      were mostly affiliated to the genera Pseudomonas and Acinetobacter. However, the
      study also widened the range of phenol-degraders by including the genus
      Limnobacter. Furthermore, using a next generation sequencing approach, the LmPH
      genes of Limnobacter strains were found to be the most prevalent ones in the
      microbial community of the Baltic Sea surface water. Four different Limnobacter
      strains having almost identical 16S rRNA gene sequences (99%) and similar
      physiological properties formed separate phylogenetic clusters of LmPH and C23O
      genes in the respective phylogenetic trees. 

PMID- 24012241
TI  - Predictors of the yield of mobilized peripheral blood CD34+ cells in HLA-matched
      sibling donor.
AB  - We examined the donor factors that may affect the yield of peripheral blood stem
      cell (PBSC) mobilized from healthy donors. Pre-apheresis PB-CD34(+) cell count
      was the only factor that correlated with PBSC yield. Leukocyte count (LC) and
      monocyte count (MC) correlated with PB-CD34(+) cell. Male gender and PB-CD34(+)
      cell count of at least 87.1/MUL and 69.8/MUL on day-4 and -5 of G-CSF were
      associated with the ability to harvest at least 5*10(6)/kg CD34(+) cells after
      one apheresis. We concluded that gender and PB-CD34(+) cell count are important
      predictors of PBSC yield. LC and MC may serve as surrogate markers for estimating
      the PB-CD34(+) cell count. 

PMID- 24012242
TI  - Riders' prediction of results at Federation Equestre Internationale (FEI)
      endurance rides and sources of bias in questionnaires completed by riders.
AB  - Information acquired from endurance riders and its relationship with the results
      of the ride has not been investigated. The aims of this study were to assess
      associations between data provided by riders and data obtained from the
      Federation Equestre Internationale (FEI) website at FEI endurance rides and to
      identify whether data provided by riders in pre- and post-ride questionnaires was
      subject to response and/or information bias. Variables were collected from the
      FEI website and from self-completed pre-ride and post-ride questionnaires at 20
      FEI endurance rides in 2011 and 2012. Kappa statistics and Mann-Whitney U-tests
      were used to assess the relationship between FEI website and questionnaire data
      and between the riders' predictions and experiences. Univariable logistic
      regression was used to investigate association between completion of the ride and
      riders' predictions. Response bias was assessed using multi-level logistic
      regression models. At least one questionnaire was completed for 236 (18.8%) of
      1254 competition starts included in the study. There was excellent agreement on
      signalment between questionnaire and FEI data, except for data on breed. There
      was moderate agreement between the mean speed category predicted by riders and
      reported in the official results. Riders with the aim of qualification or
      'competition, achieving the best possible results' were less likely to complete
      the ride than riders aiming for 'training'. Female riders, riders competing in a
      young rider class, older riders, riders competing in rides of shorter distances
      and riders that had completed the distance of the study ride more than three
      times were associated with increased likelihood of completing the questionnaires.
      In conclusion, some riders' predictions were associated with the outcome of the
      ride. A larger study is needed to assess these variables as risk factors for
      eliminations. The response biases and the difficulties of data collection
      identified in this study can help when designing future studies. 

PMID- 24012243
TI  - Neurocognitive speed associates with frontotemporal lobar degeneration TDP-43
      subtypes.
AB  - Frontotemporal lobar degeneration (FTLD) is pathologically heterogeneous with the
      TAR DNA binding protein 43 kDa (TDP-43) proteinopathy the most common substrate.
      Previous work has identified atrophy patterns across TDP-43 subtypes with Type A
      showing greater frontotemporal and parietal atrophy, Type C predominantly
      anterior temporal, and Type B predominantly posterior frontal. Despite
      neuroanatomical correlates of involvement, neuropsychological findings have been
      inconsistent. The current study utilized broader neurocognitive domains based on
      aggregated neuropsychological measures to distinguish between subtypes. We
      hypothesized that patterns of neurocognitive domain impairments would predict
      FTLD-TDP subtype. Fifty-one patients, aged 38-87, were identified post mortem
      with pathologically confirmed FTLD with TDP-43. Participants were classified into
      subtypes A, B, or C. Patients had completed neuropsychological assessments as
      part of their clinical evaluation. Six cognitive domains were created: Language;
      Cognitive Speed; Memory; Learning; Visuoperception; and Fluency. Binary logistic
      regression was conducted. All but three patients could be classified as FTLD-TDP
      Types A, B, or C: 26 as Type A; nine as Type B; and 13 as Type C. Cognitive Speed
      scores were associated with Types A and C (p < 0.001 and p = 0.003,
      respectively). Impaired performances on the Trail Making Test differentiated
      Types A and C. Worse Boston Naming Test and Logical Memory (Immediate) (p < 0.05)
      scores also increased the likelihood of Type C phenotype. Findings suggest
      Cognitive Speed associates with TDP-43 subtypes. Type C also demonstrated
      language-specific involvement. Differences between TDP-43 subtypes further
      supports the notion of differences in pathophysiology or topography across these
      types.

PMID- 24012244
TI  - A solitary hemangioblastoma located on the trochlear nerve.
AB  - Hemangioblastomas are tumors of the central nervous system that originate from
      the vascular system. They are most commonly composed of stromal cells in small
      blood vessels and usually occur in the cerebellum and spinal cord. We report a
      rare instance of a patient with a solitary hemangioblastoma located on the
      trochlear nerve. A 27-year-old woman presented with sudden onset of headache,
      vomiting, and diplopia. Imaging studies revealed a round mass lesion anterior to
      the pons with subarachnoid hemorrhage in the basal cisterns of the posterior
      fossa extending to the fourth ventricle. A biopsy confirmed it was a
      hemangioblastoma. 

PMID- 24012245
TI  - Muscle specific kinase autoimmune myasthenia gravis in children: a case series.
AB  - We report clinical, neurophysiological and autoantibody profiles of 9 children
      presenting with fatigable weakness and MuSK autoantibody seropositivity. Eight
      were female, 3 were black; median onset age was 8 years. Diplopia or bulbar
      dysfunction were common presenting symptoms. Half of the patients experienced
      moderate to severe weakness of bulbar, facial and respiratory muscles (including
      exacerbations requiring mechanical ventilation). Muscle AChR antibodies were
      detected transiently in 2 patients but no other autoantibodies were detected.
      Clinical response to treatment was variable and incomplete. No thymic
      abnormalities were noted by CT or pathologically (3 underwent thymectomy).
      Electromyographic (EMG) abnormalities (decrement of compound muscle action
      potential amplitude during slow repetitive nerve stimulation and variation in
      individual motor unit potentials) were limited to clinically weak muscles. Single
      fiber EMG demonstrated abnormalities in an asymptomatic muscle in the single
      patient studied. As in adults, MuSK autoimmune MG presents more commonly in
      females, and weakness preferentially affects bulbar, facial and respiratory
      muscles. Morbidity is significant and responses to standard therapies are
      variable and incomplete. Neurophysiological confirmation is more challenging in
      children because testing of weak muscles (cranial nerve-innervated and
      respiratory) may require moderate sedation and monitoring.

PMID- 24012246
TI  - Steroids in Duchenne dystrophy.

PMID- 24012247
TI  - Ethylene signaling: simple ligand, complex regulation.
AB  - The hormone ethylene plays numerous roles in plant development. In the last few
      years the model of ethylene signaling has evolved from an initially largely
      linear route to a much more complex pathway with multiple feedback loops.
      Identification of key transcriptional and post-transcriptional regulatory modules
      controlling expression and/or stability of the core pathway components revealed
      that ethylene perception and signaling are tightly regulated at multiple levels.
      This review describes the most current outlook on ethylene signal transduction
      and emphasizes the latest discoveries in the ethylene field that shed light on
      the mechanistic mode of action of the central pathway components CTR1 and EIN2,
      as well as on the post-transcriptional regulatory steps that modulate the
      signaling flow through the pathway. 

PMID- 24012248
TI  - Polybrominated diphenyl ethers (PBDEs) in breast milk of Korea in 2011: current
      contamination, time course variation, influencing factors and health risks.
AB  - Breast milk is a valuable biological specimen to assess maternal and infant
      exposure to polybrominated diphenyl ethers (PBDEs). In this study, 208 breast
      milk samples were collected from 89 participants during lactation period, at <7,
      15, 30, and 90 days postpartum, in four cities in Korea, and were determined for
      19 PBDE congeners. The total PBDE concentrations (SigmaPBDE) ranged from 0.23 to
      68.4 (mean: 2.73) ng/g lipid weight, and were within the ranges reported for
      European and Asian countries. Within a month of lactation after delivery, no
      significant changes were found in the PBDE concentrations. The predominance of
      BDE 153 rather than BDE 47 was found in the most samples that BDE 153 was
      detected, and was likely to be associated with stepwise debromination of BDE 209.
      No associations were found between PBDE concentrations in breast milk and
      demographic parameters, except for SigmaPBDE with maternal age and delivery mode.
      Certain types of diet such as corn, seafood and nut correlated significantly with
      PBDE levels in breast milk. The estimated daily intakes of SigmaPBDE for breast
      feeding infants were lower than the guidelines proposed by the US EPA, indicating
      limited health risk from PBDEs through breast feeding. 

PMID- 24012250
TI  - New facets of antibody deficiencies.
AB  - Antibody deficiencies are the most prevalent forms of primary immunodeficiencies
      (PIDs). Several disease-causing mutations have been identified to date, but
      still, the genetic background of most patients remains elusive. During the last 2
      years, next generation sequencing has revealed the genetic basis for a number of
      these disorders. Having as a reference the latest International Union of
      Immunological Societies classification on PIDs, we present 9 novel genetic
      defects/mechanisms that are associated with antibody deficiency, affecting either
      early or late B-cell development. The role of dysregulated autophagy in antibody
      deficiency is highlighted. The latest advance in this field provides new insights
      to our understanding of the regulation of antibody production in human B cells. 

PMID- 24012249
TI  - Synoptic weather typing applied to air pollution mortality among the elderly in
      10 Canadian cities.
AB  - BACKGROUND: Synoptic circulation patterns (large-scale weather systems) affect
      ambient levels of air pollution, as well as the relationship between air
      pollution and human health. OBJECTIVE: To investigate the air pollution-mortality
      relationship within weather types and seasons, and to determine which combination
      of atmospheric conditions may pose increased health threats in the elderly age
      categories. METHODS: The relative risk of mortality (RR) due to air pollution was
      examined using Poisson generalized linear models (GLMs) within specific weather
      types. Analysis was completed by weather type and age group (all ages, <=64, 65
      74, 75-84, >=85 years) in ten Canadian cities from 1981 to 1999. RESULTS: There
      was significant modification of RR by weather type and age. When examining the
      entire population, weather type was shown to have the greatest modifying effect
      on the risk of dying due to ozone (O3). This effect was highest on average for
      the dry tropical (DT) weather type, with the all-age RR of mortality at a
      population weighted mean (PWM) found to be 1.055 (95% CI 1.026-1.085). All
      weather type risk estimates increased with age due to exposure to carbon monoxide
      (CO), nitrogen dioxide (NO2), and sulphur dioxide (SO2). On average, RR increased
      by 2.6, 3.8 and 1.5% for the respective pollutants between the <=64 and >=85 age
      categories. Conversely, mean ozone estimates remained relatively consistent with
      age. Elevated levels of air pollution were found to be detrimental to the health
      of elderly individuals for all weather types. However, the entire population was
      negatively effected by air pollution on the hot dry (DT) and hot humid (MT) days.
      CONCLUSIONS: We identified a significant modification of RR for mortality due to
      air pollution by age, which is enhanced under specific weather types. Efforts
      should be targeted at minimizing pollutant exposure to the elderly and/or all age
      groups with respect to weather type in question.

PMID- 24012251
TI  - Predictive value of cholangioscopy after endoscopic management of early
      postcholecystectomy bile duct strictures with an increasing number of plastic
      stents: a prospective study (with videos).
AB  - BACKGROUND: Endotherapy of postcholecystectomy bile duct stricture (PCBS) has
      been established as an alternative treatment to surgery. Several studies have
      reported conflicting results regarding the predictors of success or failure of
      endotherapy. OBJECTIVE: To evaluate the different cholangioscopic appearances of
      PCBS after endotherapy with an increasing number of plastic stents and the
      predictive values of these appearances for the outcome. DESIGN: Prospective study
      with a long-term follow-up. SETTING: Two academic tertiary referral centers.
      PATIENTS: Twenty consecutive patients with major bile duct injury, with a bile
      leak, and a PCBS who underwent therapeutic ERCP. INTERVENTIONS: Closure of the
      leak followed by temporary placement of multiple plastic stents for the treatment
      of PCBS, followed by cholangioscopy at the end of endotherapy. MAIN OUTCOME
      MEASUREMENTS: To analyze the predictive value of cholangioscopy, other predictors
      of stricture recurrence after endotherapy, and long-term clinical success.
      RESULTS: Closure of the leak was achieved in all patients. The median duration of
      endotherapy was 12 months (range 7-18 months). After endoscopic stenting, the
      PCBS was considered to be appropriately dilated in all patients. After
      endotherapy, 3 different findings were noted on cholangioscopy: (1) no lesion or
      minor defect (n = 10), (2) minor stricture with a fibrous ring (n = 6), and (3)
      presence of tissue hyperplasia (n = 4). During follow-up, stricture recurrence
      developed in 4 of 20 patients. All 4 patients were successfully retreated by an
      additional period of stenting and remained free of cholestasis after a median
      follow-up period of 44 months. By Kaplan-Meier (log-rank) and univariate
      analyses, the cholangioscopic pattern of tissue hyperplasia was significantly
      associated with stricture recurrence (P < .01). LIMITATIONS: Small sample size.
      CONCLUSIONS: Endoscopic stenting should be regarded as the primary treatment of
      choice because of the successful long-term outcome after 1 or more additional
      periods of treatment. However, the cholangioscopic pattern of tissue hyperplasia
      at the time of stent removal is a strong predictor of stricture recurrence, and
      this observation may lead to an additional period of endotherapy or other
      treatment modalities.

PMID- 24012252
TI  - Not only Chauvet: dating Aurignacian rock art in Altxerri B Cave (northern
      Spain).
AB  - The discovery and first dates of the paintings in Grotte Chauvet provoked a new
      debate on the origin and characteristics of the first figurative Palaeolithic
      art. Since then, other art ensembles in France and Italy (Aldene, Fumane, Arcy
      sur-Cure and Castanet) have enlarged our knowledge of graphic activity in the
      early Upper Palaeolithic. This paper presents a chronological assessment of the
      Palaeolithic parietal ensemble in Altxerri B (northern Spain). When the study
      began in 2011, one of our main objectives was to determine the age of this
      pictorial phase in the cave. Archaeological, geological and stylistic evidence,
      together with radiometric dates, suggest an Aurignacian chronology for this art.
      The ensemble in Altxerri B can therefore be added to the small but growing number
      of sites dated in this period, corroborating the hypothesis of more complex and
      varied figurative art than had been supposed in the early Upper Palaeolithic. 

PMID- 24012253
TI  - A new partial temporal bone of a juvenile hominin from the site of Kromdraai B
      (South Africa).
AB  - The site of Kromdraai B (KB) (Gauteng, South Africa) has yielded a minimum number
      of nine hominins including the type specimen of Paranthropus robustus (TM 1517),
      the only partial skeleton of this species known to date. Four of these
      individuals are juveniles, one is a subadult and four are young adults. They all
      occur with a macrofaunal assemblage spread across the succession of at least two
      time periods that occurred in South Africa approximately two million years ago.
      Here we report on an additional, newly discovered petrous temporal bone of a
      juvenile hominin, KB 6067. Following the description of KB 6067, we assess its
      affinities with Australopithecus africanus, P. robustus and early Homo. We
      discuss its developmental age and consider its association with other juvenile
      hominin specimens found at Kromdraai B. KB 6067 probably did not reach five years
      of age and in bony labyrinth morphology it is close to P. robustus, but also to
      StW 53, a specimen with uncertain affinities. However, its cochlear and oval
      window size are closer to some hominin specimens from Sterkfontein Member 4 and
      if KB 6067 is indeed P. robustus this may represent a condition that is
      evolutionarily less derived than that shown by TM 1517 and other conspecifics
      sampled so far. The ongoing fieldwork at KB, as well as the petrography and
      geochemistry of its deposits, will help to determine when the various KB breccias
      accumulated, and how time may be an important factor underlying the variation
      seen among KB 6067 and the rest of the fossil hominin sample from this site. 

PMID- 24012254
TI  - The lethal burden of drug overdose.

PMID- 24012255
TI  - Malaria prevention: civilisation versus disease.

PMID- 24012256
TI  - Child labour: the high cost of gold.

PMID- 24012257
TI  - A turning point for clinical research in China?

PMID- 24012258
TI  - Retraction--Valsartan in a Japanese population with hypertension and other
      cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded
      endpoint morbidity-mortality study.

PMID- 24012260
TI  - HIV antiretroviral prophylaxis for injecting drug users.

PMID- 24012261
TI  - HIV antiretroviral prophylaxis for injecting drug users.

PMID- 24012262
TI  - HIV antiretroviral prophylaxis for injecting drug users.

PMID- 24012263
TI  - HIV antiretroviral prophylaxis for injecting drug users.

PMID- 24012264
TI  - HIV antiretroviral prophylaxis for injecting drug users - Authors' reply.

PMID- 24012265
TI  - First case of E anophelis outbreak in an intensive-care unit.

PMID- 24012266
TI  - Pulse oximetry screening for congenital heart defects.

PMID- 24012267
TI  - Immunisation against meningococcus B.

PMID- 24012268
TI  - Immunisation against meningococcus B.

PMID- 24012269
TI  - Immunisation against meningococcus B.

PMID- 24012270
TI  - Immunisation against meningococcus B.

PMID- 24012271
TI  - Tolosa-Hunt syndrome--a rare cause of headache and ophthalmoplegia.

PMID- 24012272
TI  - Intraoperative neurophysiologic monitoring and neurologic outcomes in patients
      with epidural spine tumors.
AB  - PURPOSE: Multimodal intraoperative neurophysiologic monitoring (IOM) provides
      assessment of spinal cord pathways during neurosurgery. Despite widespread use,
      few data exist regarding sensitivity and specificity of IOM in predicting
      neurologic outcome during decompression and instrumentation for epidural spine
      tumors. METHODS: Retrospective analysis evaluated consecutive spine procedures
      involving IOM modalities (somatosensory evoked potentials [SSEP], motor evoked
      potentials [MEP], and electromyography [(EMG]) from 2007 to 2009. Demographic and
      surgical information, intraoperative neurophysiologic data, and pre- and
      postoperative neurologic status were collected. All cases involved neoplastic
      epidural spinal cord compression by a primary or metastatic tumor and included
      posterolateral decompression and instrumented fusion. RESULTS: Two-hundred and
      eight consecutive patients had spine surgery during this time period and one
      hundred and fifty-two met inclusion criteria. All patients had SSEP monitoring,
      with 4 having transient changes and 7 persistent changes. One hundred and twenty
      two patients had combined SSEP and MEP monitoring, with 3 having transient
      changes and 4 persistent changes in MEP signals. Two patients had
      neurophysiologic changes associated with hypotension and correction led to
      normalization. One developed new neurologic deficits after surgery. Two from the
      total cohort had new postoperative neurologic deficits. One had a transient
      decrease in MEP amplitude while the other had no intraoperative changes.
      DISCUSSION: These cases are often long with significant blood loss, and stability
      of multiple IOM modalities provides reassurance that spinal cord function remains
      intact. Signal changes should result in scrutiny of blood pressure, surgical
      technique and anesthesia. Preserved IOM signals are suggestive of preserved
      neurologic outcome.

PMID- 24012273
TI  - Importance of the perforating arteries in the proximal part of the PICA for
      surgical approaches to the brain stem and fourth ventricle--an anatomical study.
AB  - OBJECTIVE: The purpose of this study is to examine the perforating arteries (PAs)
      in the proximal part of the posterior inferior cerebellar artery (PICA) for
      surgical approaches to the brain stem and fourth ventricle, and to stress their
      importance in microsurgical procedures. METHODS: Twenty-six adult cadaver
      obtained from routine autopsies were used. During the examination, the PAs and
      the segmental structure of the proximal part of the PICAs and their relation to
      the neighbouring anatomical structures were demonstrated. RESULTS: We classified
      the PICAs into 4 types on the basis of the distance of the middle point of the
      width of the caudal loop to the midline, and their presence or absence as Group A
      (symmetrical, anterior medullary type: 26.9%), Group B (lateral medullary type:
      15.4%), Group C (asymmetrical type: 38.5%), and Group D (unilateral type: 19.2%).
      The number of the PAs in the tonsillomedullary segment and the caudal loop was
      higher than those originating from the other segments. CONCLUSIONS: Approaches to
      the medial or lateral of the PICA should be made in a way that protects the PAs
      (avoiding retraction of the PICA). Otherwise the PAs will be damaged and as a
      result brain stem ischaemia may occur, which can have serious clinical outcomes.

PMID- 24012274
TI  - Fecal microbiota transplantation and donor standardization.
AB  - Clostridium difficile diarrhea is a common and severe infectious disease.
      Antibiotics, which are standard initial treatment, are less effective for
      treating refractory or recurrent infection. Fecal microbiota transplantation,
      where healthy donor stool is transplanted into a patient, is an alternative to
      antibiotic therapy that requires standardization for donors and patients.

PMID- 24012275
TI  - Synergistic impact of endurance training and intermittent hypobaric hypoxia on
      cardiac function and mitochondrial energetic and signaling.
AB  - BACKGROUND: Intermittent hypobaric-hypoxia (IHH) and endurance-training (ET) are
      cardioprotective strategies against stress-stimuli. Mitochondrial modulation
      appears to be an important step of the process. This study aimed to analyze
      whether a combination of these approaches provides additive or synergistic
      effects improving heart-mitochondrial and cardiac-function. METHODS: Two-sets of
      rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE, 1 h/day/5
      weeks treadmill-running), hypoxic-sedentary (HS, 6000 m, 5h/day/5 weeks) and
      hypoxic-exercised (HE) to study overall cardiac and mitochondrial function. In
      vitro cardiac mitochondrial oxygen consumption and transmembrane potential were
      evaluated. OXPHOS subunits and ANT protein content were semi-quantified by
      Western blotting. HIF-1alpha, VEGF, VEGF-R1 VEGF-R2, BNP, SERCA2a and PLB
      expressions were measured by qRT-PCR and cardiac function was characterized by
      echocardiography and hemodynamic parameters. RESULTS: Respiratory control ratio
      (RCR) increased in NE, HS and HE vs. NS. Susceptibility to anoxia/reoxygenation
      induced dysfunction decreased in NE, HS and HE vs. NS. HS decreased mitochondrial
      complex-I and -II subunits; however HE completely reverted the decreased content
      in complex-II subunits. ANT increased in HE. HE presented normalized ventricular
      arterial coupling (Ea) and BNP myocardial levels and significantly improved
      myocardial performance as evaluated by increased cardiac output and normalization
      of the Tei index vs. HS CONCLUSION: Data demonstrates that IHH and ET confer
      cardiac mitochondria with a more resistant phenotype although without visible
      addictive effects at least under basal conditions. It is suggested that the
      combination of both strategies, although not additive, results into improved
      cardiac function.

PMID- 24012276
TI  - Complications of transseptal catheterization for different cardiac procedures.
AB  - BACKGROUND: Cardiac tamponade is the main complication of transseptal
      catheterization that is necessary for a variety of cardiac interventions and
      electrophysiology procedures. METHODS: A retrospective assessment of all
      consecutive procedures that required transseptal puncture by the same experienced
      operator (with already >100 previous trans-septal procedures) during the period
      2000-2012 was performed. We recorded any puncture-related complications of
      pericardial effusion and cardiac tamponade (acute or delayed). RESULTS: A total
      of 393 procedures were retrieved: Group 1 [ablation of left-sided accessory
      pathways (n = 77), atrioventricular nodal reentry tachycardia-left septal access
      (AVNRT) (n = 12), and Inoue balloon mitral valvuloplasty (n = 27)], and Group 2
      [atrial fibrillation (AF) ablation procedures: ostial pulmonary vein isolation
      (PVI) (including RF (n = 76) and cryo-balloon (n = 30)), circumferential PVI (n =
      51), and combined procedures (n = 120)]. In total, 5 cases of tamponade were
      recorded, four of them were acute and one delayed (occurring 1h after the
      procedure). All tamponade cases occurred only during or after AF ablation
      procedures (cryo-balloon ablation = 1, circumferential PVI = 2, and combined
      procedures = 2). In one case emergency atrial repair following median sternotomy
      was necessary, and in another a surgical drainage through a limited thoracotomy
      was performed. The other three cases were treated with pericardiocentesis and
      drainage for 12h. No patient was on uninterrupted oral anticoagulation during the
      procedure. CONCLUSIONS: AF ablation is associated with a higher incidence of
      tamponade compared to other procedures that require transseptal access. Such
      procedures should only be performed in hospitals with access to emergency
      surgical support.

PMID- 24012277
TI  - Milk fat saturation and reproductive performance in dairy cattle.
AB  - Unsaturated fatty acids (UFA) cannot be synthesized by mammalian cells due to a
      lack of desaturase enzymes. Combined with their limited supply to the small
      intestines, UFA have been proposed as nutraceuticals to ameliorate dairy cow
      fertility. However, field studies based on a large number of animals are lacking
      on this subject. Therefore the aim of the present study was to analyze a large
      dataset containing individual cow fertility records from dairy herds and link
      fertility key-performance-indicators like conception rate to first insemination
      (CRFI), days in milk to first insemination (DIMFI) and days in milk to conception
      (DIMCONC), to the level of UFA in bulk tank samples, the latter being a proxy for
      the dietary fatty acid profile on these herds. Within the two year study period,
      information from 15,055 lactations and 35,433 bulk tank milk samples was
      collected on 90 herds. The multilevel logistic regression model used, revealed a
      decreased CRFI on herds with a higher bulk tank UFA level. The decrease in CRFI
      was larger for higher producing herds. Increased bulk tank UFA was furthermore
      associated with higher DIMFI which, together with the lower CRFI, subsequently
      increased DIMCONC. Interestingly, higher variability in UFA, expressed by an
      increased coefficient of variation, was associated with an increased CRFI and
      decreased DIMFI and DIMCONC. In conclusion, the present study demonstrates that
      increasing the UFA content of milk should not be a goal as such when
      supplementing UFA to dairy cows as higher bulk tank UFA are associated with
      worsened fertility results. 

PMID- 24012278
TI  - Plasma progesterone changes and length of oestrous cycle in Rusa Deer (Rusa
      timorensis).
AB  - A study was conducted to profile the plasma progesterone (P4) concentrations and
      establish the length of oestrous cycle in the Rusa timorensis during the breeding
      season. Five healthy hinds were selected for peripheral blood sampling twice
      weekly to gauge the P4 levels by radioimmunoassay, at the start of the breeding
      season indicated by rutting behaviours of sexually active males. The hinds were
      polyestrous as proven by the cyclic trend of P4 levels. After the presumptive
      oestrus indicated by the lowest P4 concentrations (0.20+/-0.09ng/ml), this
      ovarian hormone was markedly elevated on day 7 of the cycle (0.78+/-0.20ng/ml),
      reached its peak (2.61+/-0.23ng/ml, P<0.05) on day 14, and then declined to the
      basal level in the subsequent oestrus. The mean oestrous cycle length in R.
      timorensis during the breeding season was 19.2 days with a range of 18-21 days,
      and the pattern of circulating progesterone during the oestrous cycle of the R.
      timorensis is similar to those of other deer species. It was also observed that
      the length of oestrous cycle of R. timorensis determined by gauging the
      progesterone levels and observation of the oestrous behaviours as well as changes
      in the cellular pattern of vaginal epithelial cells are highly consistent. 

PMID- 24012279
TI  - Environmental enrichment rescues binocular matching of orientation preference in
      mice that have a precocious critical period.
AB  - Experience shapes neural circuits during critical periods in early life. The
      timing of critical periods is regulated by both genetics and the environment.
      Here we study the functional significance of such temporal regulations in the
      mouse primary visual cortex, where critical period plasticity drives binocular
      matching of orientation preference. We find that the binocular matching is
      permanently disrupted in mice that have a precocious critical period due to
      genetically enhanced inhibition. The disruption is specific to one type of
      neuron, the complex cells, which, as we reveal, normally match after the simple
      cells. Early environmental enrichment completely rescues the deficit by inducing
      histone acetylation and consequently advancing the matching process to coincide
      with the precocious plasticity. Our experiments thus demonstrate that the proper
      timing of the critical period is essential for establishing normal binocularity
      and the detrimental impact of its genetic misregulation can be ameliorated by
      environmental manipulations via epigenetic mechanisms.

PMID- 24012280
TI  - Cortical signals for rewarded actions and strategic exploration.
AB  - In stable environments, decision makers can exploit their previously learned
      strategies for optimal outcomes, while exploration might lead to better options
      in unstable environments. Here, to investigate the cortical contributions to
      exploratory behavior, we analyzed single-neuron activity recorded from four
      different cortical areas of monkeys performing a matching-pennies task and a
      visual search task, which encouraged and discouraged exploration, respectively.
      We found that neurons in multiple regions in the frontal and parietal cortex
      tended to encode signals related to previously rewarded actions more reliably
      than unrewarded actions. In addition, signals for rewarded choices in the
      supplementary eye field were attenuated during the visual search task and were
      correlated with the tendency to switch choices during the matching-pennies task.
      These results suggest that the supplementary eye field might play a unique role
      in encouraging animals to explore alternative decision-making strategies. 

PMID- 24012281
TI  - Serum adiponectin concentration in relation to macronutrient and food intake in
      young Japanese women.
AB  - OBJECTIVE: Little is known about the relation of modifiable dietary factors to
      circulating adiponectin concentrations, particularly in young adults and non
      Western populations. The aim of this study was to determine the association
      between macronutrient and food intake and serum adiponectin concentration in a
      group of young Japanese women. METHODS: This cross-sectional study included 1047
      female Japanese dietetic students aged 18 to 22 y. Using a validated, self
      administered, comprehensive diet history questionnaire, we assessed intake of
      nutrients (protein, total fat, saturated fatty acids, monounsaturated fatty
      acids, and polyunsaturated fatty acids, carbohydrates, and dietary fiber) and
      foods (rice, bread, noodles, potatoes, confectioneries, fats and oils, pulses,
      fish and shellfish, meats, eggs, dairy products, vegetables, fruits, coffee,
      green and oolong tea, black tea, and soft drinks) and glycemic index and load.
      Fasting blood samples were collected and serum adiponectin concentrations were
      measured. Adjustment was made for survey year, region, municipality level,
      current smoking, current alcohol drinking, physical activity, body mass index,
      energy intake, and intakes of other nutrients or foods. RESULTS: After adjustment
      for potential confounding factors, none of the nutrients examined was a
      significant determinant of serum adiponectin concentration. There was no
      association for glycemic index or load. Coffee was the only food significantly
      and independently associated with serum adiponectin concentration. Mean (SE)
      values of serum adiponectin concentration for each quartile of coffee intake were
      12.4 (0.2), 12.4 (0.5), 12.5 (0.3), and 13.2 (0.3) MUg/mL, respectively (P for
      trend = 0.04). CONCLUSION: In a group of young Japanese women, higher coffee
      intake was independently associated with higher serum adiponectin concentration.

PMID- 24012282
TI  - The past, present, and future of National Aeronautics and Space Administration
      spaceflight diet in support of microgravity rodent experiments.
AB  - Rodents have been the most frequently flown animal model used to study
      physiological responses to the space environment. In support of future of space
      exploration, the National Aeronautics and Space Administration (NASA) envisions
      an animal research program focused on rodents. Therefore, the development of a
      rodent diet that is suitable for the spaceflight environment including long
      duration spaceflight is a high priority. Recognizing the importance of nutrition
      in affecting spaceflight physiological responses and ensuring reliable biomedical
      and biological science return, NASA developed the nutrient-upgraded rodent food
      bar (NuRFB) as a standard diet for rodent spaceflight. Depending on future animal
      habitat hardware and planned spaceflight experiments, modification of the NuRFB
      or development of a new diet formulation may be needed, particularly for long
      term spaceflights. Research in this area consists primarily of internal technical
      reports that are not readily accessible. Therefore, the aims of this contribution
      are to provide a brief history of the development of rodent spaceflight diets, to
      review the present diet used in rodent spaceflight studies, and to discuss some
      of the challenges and potential solutions for diets to be used in future long
      term rodent spaceflight studies. 

PMID- 24012283
TI  - Edible berries: bioactive components and their effect on human health.
AB  - The importance of food consumption in relation to human health has increased
      consumer attention in nutraceutical components and foods, especially fruits and
      vegetables. Berries are a rich source of a wide variety of non-nutritive,
      nutritive, and bioactive compounds such as flavonoids, phenolics, anthocyanins,
      phenolic acids, stilbenes, and tannins, as well as nutritive compounds such as
      sugars, essential oils, carotenoids, vitamins, and minerals. Bioactive compounds
      from berries have potent antioxidant, anticancer, antimutagenic, antimicrobial,
      anti-inflammatory, and antineurodegenerative properties, both in vitro and in
      vivo. The following is a comprehensive and critical review on nutritional and non
      nutritional bioactive compounds of berries including their absorption,
      metabolism, and biological activity in relation to their potential effect on
      human health. 

PMID- 24012284
TI  - Weight loss and resting energy expenditure in male patients with newly diagnosed
      esophageal cancer.
AB  - OBJECTIVES: Cancer cachexia is associated with impaired nutritional status and
      systemic inflammation. The goal of this study was to evaluate the nutritional
      status and resting energy expenditure (REE) changes in patients with newly
      detected esophageal cancer, and the influence of weight loss on REE. METHODS:
      Fifty-six patients and 30 healthy controls were prospectively enrolled, and
      patients were further divided into weight-stable (WS) and weight-loss (WL)
      subgroups. Body composition, measured REE (mREE), and the ratio of mREE to
      predicted REE (pREE) by Harris-Benedict formula were assessed. Blood levels of
      hemoglobin, albumin, prealbumin, high-sensitivity C-reactive protein (hs-CRP),
      tumor necrosis factor-alpha (TNF-alpha), and interleukin (IL)-6 were measured in
      patients. RESULTS: Cancer patients had lower body mass index (BMI) and percentage
      of fat mass, but higher mREE and percentage of mREE/pREE compared with healthy
      controls (P < 0.05). WS (n = 32) and WL patients (n = 24) had similar BMI and
      body composition indices, but the latter had obviously higher mREE, mREE per
      kilogram body weight (mREE/BW), percentage of mREE/pREE, hs-CRP and IL-6 levels,
      and lower albumin and prealbumin levels. Percentage of weight loss was positively
      correlated with REE/BW, hs-CRP, and IL-6 level (r = 0.238, P = 0.044; r = 0.446,
      P = 0.01; r = 0.196, P = 0.047, respectively). CONCLUSION: Impaired nutrition
      status, elevated energy expenditure, and higher inflammation status tend to be
      apparent in weight-losing patients with newly diagnosed esophageal cancer, which
      suggested that early recognition of body weight change and routine nutritional
      risk screening followed by adequate nutrition intervention should be applied in
      these patients.

PMID- 24012285
TI  - An incidental posterior mediastinal mass.

PMID- 24012286
TI  - Clinical presentation and percutaneous endovascular management of acute left
      subclavian artery thrombosis: report of two cases.

PMID- 24012287
TI  - PET-CT and diagnostic CT: the synergy of metabolic and morphological data in onco
      haematology.
AB  - PURPOSE: Our goal was to determine how interpreting diagnostic CT together with
      PET-CT could improve the assessment of morphology in onco-haematology. PATIENTS
      AND METHODS: Fifty-nine patients with aggressive lymphoma were retrospectively
      included. The diagnostic CT scan was interpreted by two radiologists, followed by
      a combined analysis of the CT and the PET-CT carried out by two specialists in
      metabolic and morphological imaging. The diagnostic performances were assessed in
      terms of sensitivity and specificity, then concordance and discordance rates
      (kappa) were studied. RESULTS: A combined interpretation of CT and PET-CT showed
      better diagnostic performances than those of interpretations of CT only in the
      assessment of nodal sites (826 sites, sensitivity of 99% versus 85%, P<0.05),
      extranodal sites (649 sites, sensitivity of 88% versus 78%) and bone sites (one
      analysed per patient, sensitivity of 50% versus 27%). The combined interpretation
      also improved inter-observer agreement and led to an upgraded Ann Arbor staging
      in 15% of patients, with a change of treatment in 10%. CONCLUSION: Interpretation
      of diagnostic CT in onco-haematology can be improved by combining it with an
      assessment of PET-CT. The synergy between metabolic and morphological information
      leads to improved diagnostic capabilities and renders interpretations more
      reproducible.

PMID- 24012288
TI  - Cause-specific mortality among patients with psychosis: disentangling the effects
      of age and illness duration.
AB  - BACKGROUND: There is a large mortality gap between patients with a nonaffective
      psychotic disorder and those in the general population, is associated with both
      natural and nonnatural death causes. OBJECTIVE: This study aims to assess whether
      mortality risks vary for different causes of death according to the duration
      since diagnosis and age in a large sample of patients with nonaffective psychotic
      disorder. METHODS: Data of patients with nonaffective psychotic disorder (n =
      12,580) from 3 Dutch psychiatric registers were linked to the cause of death
      register of Statistics Netherlands and compared with personally matched controls
      (n = 124,143) from the population register. Death rates were analyzed by duration
      since the date of the registered diagnosis of the (matched) patient and their age
      using a Poisson model. RESULTS: Among patients, the rates of all-cause death
      decreased with longer illness duration. This was explained by lower suicide
      rates. For example, among those between 40 and 60 years of age, the rate ratios
      (RR) of suicide during 2-5 and > 5 years were 0.52 and 0.46 (p = 0.002),
      respectively, when compared with the early years after diagnosis. Compared with
      controls, patients experienced higher rates of natural death causes during all
      stages and in all age categories, rate ratios 2.35-5.04; p < 0.001-0.025. There
      was no increase in these rate ratios with increasing duration or increasing age
      for patients when compared with controls. CONCLUSIONS: The high risk of natural
      death causes among patients with nonaffective psychotic disorder is already
      present at a comparatively young age. This suggests caution in blaming
      antipsychotics or the accumulating effects of adverse lifestyle factors for
      premature death. It is better to proactively monitor and treat somatic problems
      from the earliest disease stages onward.

PMID- 24012289
TI  - Psychogenic adipsia presenting as acute kidney injury: case report and review of
      disorders of sodium and water metabolism in psychiatric illness.

PMID- 24012290
TI  - The state of the service: a survey of psychiatry resident education in
      psychosomatic medicine.
AB  - BACKGROUND: Although required by the Accreditation Council for Graduate Medical
      Education, training of general psychiatry residents in Psychosomatic Medicine
      (PM) varies significantly between programs. In 1996, the Academy of Psychosomatic
      Medicine (APM) developed guidelines for residency training in PM. Since then,
      there has been no assessment of the status of PM training during psychiatry
      residency. OBJECTIVE: Assessment of the current state of PM training in U.S.
      psychiatry residency programs. METHOD: A 46-item questionnaire was sent via e
      mail to 206 residency directors. Four major areas were assessed: the timing and
      duration of the PM rotation, level of faculty supervision, didactic curriculum,
      and role (or potential role) of the APM in residency education. RESULTS: Ninety
      two surveys were returned (response rate 45%). Forty-four (54%) of the general
      psychiatry residencies reported the total duration of the C-L rotation as being
      between 3 and 6 months (including both full- and part-time rotation). Only 38
      (46%) programs' residents complete their PM experience in 1 year of residency.
      The average Full-Time Equivalent of teaching faculty per service was 1.74
      (standard deviation 0.92). Sixty-four (77%) programs have a formal didactic
      curriculum in C-L. Eighty-one (98%) respondents were aware of the APM. Fifty
      eight (70%) had APM members among faculty. The most popular responses on how the
      APM could best serve training programs were the creation of a subspecialty
      curriculum (73%) as well as the development of a competency-based evaluation tool
      (66%). CONCLUSIONS: There is significant variation in how residents are taught PM
      during their training. The APM is a well-recognized organization that may define
      what constitutes adequate residency training in PM and may help programs fulfill
      the educational needs of residents.

PMID- 24012291
TI  - Resolution of acute disseminated encephalomyelitis following termination of
      pregnancy.

PMID- 24012292
TI  - A prospective study of ideal cardiovascular health and depressive symptoms.
AB  - BACKGROUND: Ideal cardiovascular health is a new construct defined by the
      American Heart Association as part of its 2020 Impact Goal. OBJECTIVE: The
      purpose of this study was to examine whether the simultaneous presence of ideal
      cardiovascular health behaviors and factors could reduce the odds of developing
      depressive symptoms. METHODS: Participants from the Aerobics Center Longitudinal
      Study, who did not have any mental disorder/condition at baseline, were examined
      between 1987 and 1998, and they were followed up for a mean period of 6.1 years.
      Ideal cardiovascular health behaviors (never smoking, body mass index <25kg/m(2),
      physical activity at goal, and appropriate diet consistent with guideline
      recommendations) and factors (total cholesterol <200mg/dL, blood pressure
      <120/80mm Hg, and fasting blood glucose <100mg/dL) were measured at baseline.
      Depressive symptoms were assessed using the 10-item Center for Epidemiologic
      Studies Depression Scale in 1990, 1995, or 1999. RESULTS: Of the 5110
      participants, 641 reported depressive symptoms. Participants meeting 3-4 or 5-7
      ideal cardiovascular health components had 28% (odds ratio = 0.72; 95% confidence
      interval 0.59-0.87) and 36% (odds ratio = 0.64; confidence interval 0.50-0.82)
      decreased odds of depressive symptoms, respectively, when compared with those
      meeting 0-2 ideal components. Ideal behaviors were associated with lower odds of
      depressive symptoms in participants meeting 2 or 3-4 ideal behaviors, compared
      with those meeting 0-1 (odds ratio = 0.81; confidence interval 0.67-0.98 and odds
      ratio = 0.72; confidence interval 0.57-0.91). Ideal factors were not associated
      with depressive symptoms. CONCLUSION: Ideal cardiovascular health components,
      especially health behaviors, present an inverse relationship with depressive
      symptoms.

PMID- 24012293
TI  - Antidepressant pretreatment for the prevention of interferon alfa-associated
      depression: a systematic review and meta-analysis.
AB  - BACKGROUND: Depression is a major complication during treatment with interferon
      alfa (IFN-alpha). AIM: The aim of this study was to clarify whether preemptive
      antidepressant treatment can reduce the incidence and severity of IFN-associated
      depression. METHOD: Based on a systematic review of the literature up to July
      2012, a meta-analysis of the data from 8 trials investigating patients with
      malignant melanoma or hepatitis C was performed. The influence of antidepressants
      on the incidence of major depression and depression severity was defined as the
      primary outcome and the influence of somatic disorder, psychiatric comorbidity,
      type of antidepressants, type of IFN, and possible effects on treatment outcome
      as secondary outcome criteria. RESULTS: Antidepressant pretreatment reduced the
      overall incidence of major depression during IFN treatment in all patients (odds
      ratio = 0.42; 95% confidence interval, 0.26-0.68; p < 0.001, n = 589) and was
      associated with lower mean depression scores after 12 weeks of IFN treatment (g =
      -0.37; 95% confidence interval -0.59 to -0.18; p < 0.001, n = 375). For patients
      with hepatitis C virus infection, antidepressants reduced the incidence of major
      depression (odds ratio = 0.38; 95% confidence interval 0.22-0.66; p < 0.001, n =
      549) and the mean depression scores after 24 weeks of IFN treatment (g = -0.50;
      95% confidence interval -0.70 to -0.29; p < 0.001, n = 335). The effects of
      selective serotonin reuptake inhibitors on the incidence and severity of
      depression were not dependent on pre-existing psychiatric disorders. CONCLUSION:
      Antidepressant pretreatment with selective serotonin reuptake inhibitors lowers
      the incidence and severity of IFN-associated depression in patients with chronic
      hepatitis C infection or malignant melanoma.

PMID- 24012294
TI  - Disruptive innovations: new anti-infectives in the age of resistance.
AB  - This special issue of Current Opinion in Pharmacology is concerned with new
      developments in antimicrobial drugs and covers innovative strategies for dealing
      with microbial infection in the age of multi-antibiotic resistance. Despite
      widespread fears that many infectious diseases may become untreatable, disruptive
      innovations are in the process of being discovered and developed that may go some
      way to leading the fight-back against the rising threat. Natural products, quorum
      sensing inhibitors, biofilm disruptors, gallium-based drugs, cyclodextrin
      inhibitors of pore-forming toxins, anti-fungals that deal with biofilms, and
      light based antimicrobial strategies are specifically addressed. New non
      vertebrate animal models of infection may facilitate high-throughput screening
      (HTS) of novel anti-infectives. 

PMID- 24012295
TI  - Diabetic foot ulcer incidence in relation to plantar pressure magnitude and
      measurement location.
AB  - AIMS: We prospectively examined the relationship between site-specific peak
      plantar pressure (PPP) and ulcer risk. Researchers have previously reported
      associations between diabetic foot ulcer and elevated plantar foot pressure, but
      the effect of location-specific pressures has not been studied. METHODS: Diabetic
      subjects (n=591) were enrolled from a single VA hospital. Five measurements of in
      shoe plantar pressure were collected using F-Scan. Pressures were measured at 8
      areas: heel, lateral midfoot, medial midfoot, first metatarsal, second through
      fourth metatarsal, fifth metatarsal, hallux, and other toes. The relationship
      between incident plantar foot ulcer and PPP or pressure-time integral (PTI) was
      assessed using Cox regression. RESULTS: During follow-up (2.4years), 47 subjects
      developed plantar ulcers (10 heel, 12 metatarsal, 19 hallux, 6 other). Overall
      mean PPP was higher for ulcer subjects (219 vs. 194kPa), but the relationship
      differed by site (the metatarsals with ulcers had higher pressure, while the
      opposite was true for the hallux and heel). A statistical analysis was not
      performed on the means, but hazard ratios from a Cox survival analysis were
      nonsignificant for PPP across all sites and when adjusted for location. However,
      when the metatarsals were considered separately, higher baseline PPP was
      significantly associated with greater ulcer risk; at other sites, this
      relationship was nonsignificant. Hazard ratios for all PTI data were
      nonsignificant. CONCLUSIONS: Location must be considered when assessing the
      relationship between PPP and plantar ulceration.

PMID- 24012296
TI  - Wound classification in pediatric general surgery: significant variation exists
      among providers.
AB  - BACKGROUND: Risk-adjusted rates of surgical site infections (SSI) are used as a
      quality metric to facilitate improvement within a hospital system and allow
      comparison across institutions. The NSQIP-Pediatric, among others, uses surgical
      wound classification as a variable in models designed to predict risk-adjusted
      postoperative morbidity, including SSI rates. The purpose of this study was to
      measure the level of agreement in wound classification assignment among 3
      providers: surgeons, operating room (OR) nurses, and NSQIP surgical clinical
      reviewers (SCR). STUDY DESIGN: An analysis was performed of pediatric general
      surgery operations from 2010 to 2011. Wound classification was assigned at the
      time of operation by the OR nurse and surgeon, and by the NSQIP SCR
      postoperatively, according to NSQIP methodology. Disagreement was defined as any
      discrepancy in classification among the 3 providers, and the level of agreement
      was determined using the kappa statistic. RESULTS: For the 374 procedures
      reviewed, there was an overall disagreement of 48% among all providers, kappa
      0.48 (95% CI 0.43 to 0.53). When comparing wound classification by surgeon and
      NSQIP SCR, 23% of cases were in disagreement, kappa 0.74 (95% CI 0.68 to 0.78).
      Disagreement between OR nurse and either surgeon or NSQIP SCR was higher: 38%,
      kappa 0.45 (95% CI 0.38 to 0.53) and 40%, kappa 0.44 (95% CI 0.37 to 0.51).
      Fundoplication, appendectomy, and cholecystectomy demonstrated the highest
      overall disagreement (73%, 71%, and 60%, respectively). CONCLUSIONS: There is
      significant variation in assigning surgical wound classification among health
      care providers. For future SSI comparative analyses, it will be critical to
      improve uniformity and understanding of wound class assignment among providers
      and institutions.

PMID- 24012297
TI  - The "hidden curriculum" and residents' attitudes about medical error disclosure:
      comparison of surgical and nonsurgical residents.
AB  - BACKGROUND: The "hidden curriculum" and role models for responding to medical
      errors might play a central role in influencing residents' attitudes about
      disclosure. We sought to compare surgical and nonsurgical residents' exposure to
      role modeling for responding to medical errors and their attitudes about error
      disclosure. STUDY DESIGN: We conducted a cross-sectional, electronic survey of
      surgical and nonsurgical residents at 2 large academic medical centers. The
      questionnaire asked respondents about personal experience with medical errors;
      training for responding to errors; frequency of exposure to role modeling related
      to disclosure; and attitudes about disclosure. Descriptive statistics were used
      to describe frequencies. Chi-square and Fisher's exact test were used to compare
      proportions between surgical and nonsurgical trainees. RESULTS: The response rate
      was 58% (253 of 435). Surgical residents reported more frequently observing a
      colleague be treated harshly (eg, humiliated or verbally abused) for an error
      than nonsurgical residents (sometimes or often, 39% [26 of 66] vs 20% [37 of
      187]; p = 0.002). Surgical residents were more likely than nonsurgical residents
      to believe they would be treated harshly by others if they acknowledged making a
      medical error (35% [23 of 66] vs 12% [23 of 187]; p < 0.001) and believe they
      have to compromise their own values when dealing with medical errors at their
      institution (11% [7 of 66] vs 2% [4 of 187]; p = 0.008). Surgical residents were
      less likely than nonsurgical residents to feel free to express concerns to other
      members of the team about medical errors in patient care (70% [46 of 66] vs 83%
      [115 of 187]; p = 0.02). CONCLUSIONS: The punitive response to error by senior
      members of the health care team might be an impediment to the transparent
      disclosure of errors among residents that might disproportionally affect surgical
      training programs.

PMID- 24012298
TI  - Liposome-mediated mycelial transformation of filamentous fungi.
AB  - Liposome-mediated transformation is common for cells with no cell wall, but has
      very limited usage in cells with walls, such as bacteria, fungi, and plants. In
      this study, we developed a procedure to introduce DNA into mycelium of
      filamentous fungi, Rhizopus nigricans LH 21 and Pleurotus ostreatus TD 300, by
      liposome-mediation but with no protoplast preparation. The DNA was transformed
      into R. nigricans via plasmid pEGFP-C1 and into P. ostreatus via 7.2 kb linear
      DNA. The mycelia were ground in 0.6 M mannitol without any grinding aids or glass
      powder for 15 min to make mycelial fragments suspension; the suspension was mixed
      with a mixture of the DNA and Lipofectamine 2000, and placed on ice for 30 min;
      100 MUL of the transformation solution was plated on potato dextrose agar (PDA)
      plate and cultivated at 28  degrees C for transformant screening. The plasmid and
      the linear DNA were confirmed to be integrated into the host chromosome, proving
      the success of transformation. The transformation efficiencies were similar to
      those of electroporation-mediated protoplast transformation (EMPT) of R.
      nigricans or PEG/CaCl2-mediated protoplast transformation (PMT) of P. ostreatus,
      respectively. The results showed that our procedure was effective, fast, and
      simple transformation method for filamentous fungi.

PMID- 24012299
TI  - Starting from scratch: Evolution of the lichen thallus in the basidiolichen
      Dictyonema (Agaricales: Hygrophoraceae).
AB  - Phylogenetic studies indicate that the basidiolichen genus Dictyonema s.lat.,
      often thought to represent only a single genus with few species, includes several
      well-supported genus-level clades, all of which form associations with a unique
      lineage of obligately lichenized cyanobacteria (Rhizonema). In an attempt to
      elucidate the evolution and genus- and species-level diversification in
      Dictyonema s.lat., we generated 68 new sequences of the nuclear large subunit
      rDNA (nuLSU), the internal transcribed spacer (ITS), and the RNA polymerase II
      subunit (RPB2), for 29 species-level lineages representing all major clades of
      Dictyonema s.lat. and most of the species currently known. The multilocus
      phylogeny obtained via maximum likelihood and Bayesian approaches indicates the
      presence of five genus-level groups: a basal clade, Cyphellostereum, that is
      sister to the rest of the species, a paraphyletic grade representing Dictyonema
      s.str., and three clades representing the genera Acantholichen, Cora, and
      Corella. To determine the evolutionary transformations of the lichenized thallus
      in the group, ancestral character state reconstruction was done using six
      characters (lichenisation, thallus type, cortex type, hyphal sheath and
      haustorial type, photobiont morphology, and basidiocarp type). Our analysis
      indicates a progressive development of the lichenized thallus from loosely
      organized filamentous crusts with separate, cyphelloid basidiocarps in
      Cyphellostereum, to filamentous crusts with derived hyphal sheath and cyphelloid
      stereoid basidiocarps partially incorporated into the lichen thallus in
      Dictyonema, to squamulose-foliose thalli with corticioid basidiocarps entirely
      supported by the lichen thallus in Cora. These results indicate a remarkable
      evolutionary integration of lichenized and reproductive tissues in Dictyonema
      s.lat., supporting the hypothesis that, at least in this case, lichenized thalli
      may have evolved from reproductive structures in their nonlichenized ancestors.

PMID- 24012300
TI  - Isolation of the MAT1-1 mating type idiomorph and evidence for selfing in the
      Chinese medicinal fungus Ophiocordyceps sinensis.
AB  - Ophiocordyceps sinensis is one of the most valued medicinal fungi in China.
      Research on the mating system and sexual development is vitally important to this
      endangered species. Previous efforts devoted to investigate the mating type (MAT)
      locus of O. sinensis, however, resulted in an incomplete understanding. In this
      study, the MAT1-1 locus of O. sinensis was investigated. The conserved alpha-box
      and HMG-box regions of the MAT1-1-1 and MAT1-1-3 genes, respectively, and a
      conserved region of the DNA lyase gene were successfully amplified using
      degenerate PCR. A combination of TAIL-PCR and long-range PCR were used to connect
      these genes and obtain the sequence of the MAT1-1 locus. Screening of 22 single
      spore isolates by PCR demonstrated that both the MAT1-1-1 and MAT1-2-1 genes
      cooccurred within the same isolate. Additionally, both MAT1-1-1 and MAT1-2-1 are
      expressed in vegetative mycelia, providing evidence that O. sinensis is likely
      capable of selfing. DAPI (4,6-diamidino-2-phenylindole) staining of ascospores
      and hyphae showed that a majority of hyphal compartments are binucleate,
      suggesting that O. sinensis may be pseudohomothallic. Analyses of sequence
      diversity showed lower levels of genetic diversity in MAT1-1-1 compared to MAT1-2
      1, indicating the possibility that different selective pressures act on the two
      MAT idiomorphs. The MAT1-1-1 sequences of O. sinensis and Tolypocladium inflatum
      cluster as a monophyletic group consistent with phylogenetic classification of
      Ophiocordycipitaceae. Comparison of the structure of the MAT1-1 locus across
      hypocrealean taxa showed that O. sinensis contains all three mating type genes
      (MAT1-1-1, MAT1-1-2, and MAT1-1-3) and supported previous observations that of
      the four families in Hypocreales, MAT1-1-3 has undergone a lineage specific loss
      only in some members of the Cordycipitaceae. 

PMID- 24012301
TI  - The phylogenetic placement of hypocrealean insect pathogens in the genus
      Polycephalomyces: an application of One Fungus One Name.
AB  - Understanding the systematics and evolution of clavicipitoid fungi has been
      greatly aided by the application of molecular phylogenetics. They are now
      classified in three families, largely driven by reevaluation of the
      morphologically and ecologically diverse genus Cordyceps. Although reevaluation
      of morphological features of both sexual and asexual states were often found to
      reflect the structure of phylogenies based on molecular data, many species remain
      of uncertain placement due to a lack of reliable data or conflicting
      morphological characters. A rigid, darkly pigmented stipe and the production of a
      Hirsutella-like anamorph in culture were taken as evidence for the transfer of
      the species Cordyceps cuboidea, Cordyceps prolifica, and Cordyceps ryogamiensis
      to the genus Ophiocordyceps. Data from ribosomal DNA supported these species as a
      single group, but were unable to infer deeper relationships in Hypocreales. Here,
      molecular data for ribosomal and protein coding DNA from specimens of
      Ophiocordyceps cuboidea, Ophiocordyceps ryogamiensis, Ophiocordyceps
      paracuboidea, Ophiocordyceps prolifica, Cordyceps ramosopulvinata, Cordyceps
      nipponica, and isolates of Polycephalomyces were combined with a broadly sampled
      dataset of Hypocreales. Phylogenetic analyses of these data revealed that these
      species represent a clade distinct from the other clavicipitoid genera. Applying
      the recently adopted single system of nomenclature, new taxonomic combinations
      are proposed for these species in the genus Polycephalomyces, which has been
      historically reserved for asexual or anamorphic taxa.

PMID- 24012302
TI  - Identification, molecular characterization, and evolution of group I introns at
      the expansion segment D11 of 28S rDNA in Rhizoctonia species.
AB  - The nuclear ribosomal DNA of Rhizoctonia species is polymorphic in terms of the
      nucleotide composition and length. Insertions of 349-410 nucleotides in length
      with characteristics of group I introns were detected at a single insertion point
      at the expansion segment D11 of 28S rDNA in 12 out of 64 isolates. Eleven
      corresponded to Rhizoctonia solani (teleomorph: Thanatephorous) and one (AG-Q) to
      Rhizoctonia spp. (teleomorph: Ceratobasidium). Sequence data showed that all but
      AG-Q contained conserved DNA catalytic core regions (P, Q, R, and S) essential
      for selfsplicing. The predicted secondary structure revealed that base-paired
      helices corresponded to subgroup IC1. Isolates from same anastomosis group and
      even subgroups within R. solani were variable with regard to possession of
      introns. Phylogenetic analyses indicated that introns were vertically
      transmitted. Unfortunately, sequence data from the conserved region from all 64
      isolates were not useful for delimiting species. Analyses with IC1 introns at
      same insertion point, of both Ascomycota and Basidiomycota indicated the
      possibility of horizontal transfer at this site. The present study uncovered new
      questions on evolutionary pattern of change of these introns within Rhizoctonia
      species.

PMID- 24012304
TI  - Comparison of growth, nutritional utilisation patterns, and niche overlap indices
      of toxigenic and atoxigenic Aspergillus flavus strains.
AB  - The effects of temperatures (20-30  degrees C) and water activity (0.90-0.99 aw)
      on the lag phase duration, mycelial growth, and nutritional utilisation patterns
      of two toxigenic (AFL1(+) & AFL2(+)) and three atoxigenic (AFL1(-), AFL2(-), &
      AFL3(-)) Aspergillus flavus strains were evaluated in vitro. Both temperature and
      aw and their interactions had a significant influence on the growth and
      nutritional utilisation patterns (p < 0.05). There were no significant
      differences between toxigenic and atoxigenic strains in terms of lag phase prior
      to growth and mycelial growth rates. Based on carbon source (CS) utilisation
      patterns, toxigenic and atoxigenic strains' niche size was greater at higher
      temperatures and in wetter conditions. Additionally, based on niche overlap
      indices (NOIs), regardless of temperature, when water was freely available,
      atoxigenic and toxigenic strains co-existed. However, under moisture stress, the
      nutritional competitiveness was variable. Temporal carbon utilisation sequences
      (TCUS) of toxigenic and atoxigenic strains were compared. At 0.99 aw most CS
      sources were utilised by the strains and the time to detection (TTD) of each
      strain was shortest on monosaccharides at the same level of aw. Conversely, under
      moisture stress the least number of CS was utilised. The current study has
      demonstrated that carbon utilisation patterns are equally important as are other
      determinants of competitiveness and that growth rate alone is not a key attribute
      which determines competitiveness.

PMID- 24012303
TI  - Phylogenetic evaluation of Geomyces and allies reveals no close relatives of
      Pseudogymnoascus destructans, comb. nov., in bat hibernacula of eastern North
      America.
AB  - White-nose syndrome (WNS) of bats, caused by the fungus previously known as
      Geomyces destructans, has decimated populations of insectivorous bats in eastern
      North America. Recent work on fungi associated with bat hibernacula uncovered a
      large number of species of Geomyces and allies, far exceeding the number of
      described species. Communication about these species has been hindered by the
      lack of a modern taxonomic evaluation, and a phylogenetic framework of the group
      is needed to understand the origin of G. destructans and to target closely
      related species and their genomes for the purposes of understanding mechanisms of
      pathogenicity. We addressed these issues by generating DNA sequence data for the
      internal transcribed spacer (ITS) region, nuclear large subunit (LSU) rDNA, MCM7,
      RPB2, and TEF1 from a diverse array of Geomyces and allies that included isolates
      recovered from bat hibernacula as well as those that represent important type
      species. Phylogenetic analyses indicate Geomyces and allies should be classified
      in the family Pseudeurotiaceae, and the genera Geomyces, Gymnostellatospora, and
      Pseudogymnoascus should be recognized as distinct. True Geomyces are restricted
      to a basal lineage based on phylogenetic placement of the type species, Geomyces
      auratus. Thus, G. destructans is placed in genus Pseudogymnoascus. The closest
      relatives of Pseudogymnoascus destructans are members of the Pseudogymnoascus
      roseus species complex, however, the isolated and long branch of P. destructans
      indicates that none of the species included in this study are closely related,
      thus providing further support to the hypothesis that this pathogen is non-native
      and invasive in eastern North America. Several conidia-producing isolates from
      bat hibernacula previously identified as members of Pseudeurotium are determined
      to belong to the genus Leuconeurospora, which is widespread, especially in colder
      regions. Teberdinia hygrophila is transferred to Pseudeurotium as Pseudeurotium
      hygrophilum, comb. nov., in accordance with the one name per fungus system of
      classification, and two additional combinations are made in Pseudogymnoascus
      including Pseudogymnoascus carnis and Pseudogymnoascus pannorum. Additional
      sampling from other regions of the world is needed to better understand the
      evolution and biogeography of this important and diverse group of fungi.

PMID- 24012305
TI  - The molecular phylogeny of aquatic hyphomycetes with affinity to the
      Leotiomycetes.
AB  - Aquatic hyphomycetes play a key role in decomposition of submerged organic matter
      and stream ecosystem functioning. We examined the phylogenetic relationships
      among various genera of aquatic hyphomycetes belonging to the Leotiomycetes
      (Ascomycota) using sequences of internal transcribed spacer (ITS) and large
      subunit (LSU) regions of rDNA generated from 42 pure cultures including 19 ex
      types. These new sequence data were analyzed together with additional sequences
      from 36 aquatic hyphomycetes and 60 related fungi obtained from GenBank. Aquatic
      hyphomycetes, characterized by their tetraradiate or sigmoid conidia, were
      scattered in nine supported clades within the Helotiales (Leotiomycetes).
      Tricladium, Lemonniera, Articulospora, Anguillospora, Varicosporium,
      Filosporella, and Flagellospora are not monophyletic, with species from the same
      genus distributed among several major clades. The Gyoerffyella clade and the
      Hymenoscyphus clade accommodated species from eight and six different genera,
      respectively. Thirteen aquatic hyphomycete taxa were grouped in the Leotia
      Bulgaria clade while twelve species clustered within the Hymenoscyphus clade
      along with several amphibious ascomycetes. Species of Filosporella and some
      species from four other aquatic genera were placed in the Ascocoryne-Hydrocina
      clade. It is evident that many aquatic hyphomycetes have relatives of terrestrial
      origin. Adaptation to colonize the aquatic environment has evolved independently
      in multiple phylogenetic lineages within the Leotiomycetes.

PMID- 24012306
TI  - Laplacian based non-local means denoising of MR images with Rician noise.
AB  - Magnetic Resonance (MR) image is often corrupted with a complex white Gaussian
      noise (Rician noise) which is signal dependent. Considering the special
      characteristics of Rician noise, we carry out nonlocal means denoising on squared
      magnitude images and compensate the introduced bias. In this paper, we propose an
      algorithm which not only preserves the edges and fine structures but also
      performs efficient denoising. For this purpose we have used a Laplacian of
      Gaussian (LoG) filter in conjunction with a nonlocal means filter (NLM). Further,
      to enhance the edges and to accelerate the filtering process, only a few similar
      patches have been preselected on the basis of closeness in edge and inverted mean
      values. Experiments have been conducted on both simulated and clinical data sets.
      The qualitative and quantitative measures demonstrate the efficacy of the
      proposed method. 

PMID- 24012307
TI  - Western Thoracic Surgical Association 2013 presidential address: winning the
      HITECH challenge.

PMID- 24012309
TI  - Intra-articular osteoid osteoma of the lateral tibial plateau treated with
      arthroscopically assisted removal and retrograde osteochondral grafting.
AB  - The treatment of an intra-articular osteoid osteoma is sometimes challenging,
      because of its location. We report a patient with an intra-articular osteoid
      osteoma of the lateral tibial plateau which was excised under an arthroscopically
      assisted procedure. After total resection of the intra-articular osteoid osteoma,
      the osteochondral defect of the lateral tibial plateau was reconstructed with a
      retrograde autogenous osteochondral graft which was harvested from the non
      weightbearing area of the distal femur. 

PMID- 24012308
TI  - Understanding of dopant-induced osteogenesis and angiogenesis in calcium
      phosphate ceramics.
AB  - General trends in synthetic bone grafting materials are shifting towards
      approaches that can illicit osteoinductive properties. Pharmacologics and
      biologics have been used in combination with calcium phosphate (CaP) ceramics,
      however, they have recently become the target of scrutiny over safety. The
      importance of trace elements in natural bone health is well documented. Ions, for
      example, lithium, zinc, magnesium, manganese, silicon, strontium, etc., have been
      shown to increase osteogenesis and neovascularization. Incorporation of dopants
      (trace metal ions) into CaPs can provide a platform for safe and efficient
      delivery in clinical applications where increased bone healing is favorable. This
      review highlights the use of trace elements in CaP biomaterials, and offers an
      insight into the mechanisms of how metal ions can enhance both osteogenesis and
      angiogenesis. 

PMID- 24012310
TI  - A shared representation of the space near oneself and others in the human
      premotor cortex.
AB  - Interactions between people require shared high-level cognitive representations
      of action goals, intentions, and mental states, but do people also share their
      representation of space? The human ventral premotor (PMv) and parietal cortices
      contain neuronal populations coding for the execution and observation of actions,
      analogous to the mirror neurons identified in monkeys. This neuronal system is
      tuned to the location of the acting person relative to the observer and the
      target of the action. Therefore, it can be theorized that the observer's brain
      constructs a low-level, body-centered representation of the space around others
      similar to one's own peripersonal space representation. Single-cell recordings
      have reported that parietal visuotactile neurons discharge for objects near
      specific parts of a monkey's own body and near the corresponding body parts of
      another individual. In humans, no neuroimaging study has investigated this issue.
      Here, we identified neuronal populations in the human PMv that encode the space
      near both one's own hand and another person's hand. The shared peripersonal space
      representation could support social interactions by coding sensory events,
      actions, and cognitive processes in a common spatial reference frame.

PMID- 24012311
TI  - Learning optimizes decision templates in the human visual cortex.
AB  - Translating sensory information into perceptual decisions is a core challenge
      faced by the brain. This ability is understood to rely on weighting sensory
      evidence in order to form mental templates of the critical differences between
      objects. Learning is shown to optimize these templates for efficient task
      performance, but the neural mechanisms underlying this improvement remain
      unknown. Here, we identify the mechanisms that the brain uses to implement
      templates for perceptual decisions through experience. We trained observers to
      discriminate visual forms that were randomly perturbed by noise. To characterize
      the internal stimulus template that observers learn when performing this task, we
      adopted a classification image approach (e.g., [5-7]) for the analysis of both
      behavioral and fMRI data. By reverse correlating behavioral and multivoxel
      pattern responses with noisy stimulus trials, we identified the critical image
      parts that determine the observers' choice. Observers learned to integrate
      information across locations and weight the discriminative image parts. Training
      enhanced shape processing in the lateral occipital area, which was shown to
      reflect size-invariant representations of informative image parts. Our findings
      demonstrate that learning optimizes mental templates for perceptual decisions by
      tuning the representation of informative image parts in higher ventral cortex.

PMID- 24012312
TI  - Coral bleaching independent of photosynthetic activity.
AB  - The global decline of reef-building corals is due in part to the loss of algal
      symbionts, or "bleaching," during the increasingly frequent periods of high
      seawater temperatures. During bleaching, endosymbiotic dinoflagellate algae
      (Symbiodinium spp.) either are lost from the animal tissue or lose their
      photosynthetic pigments, resulting in host mortality if the Symbiodinium
      populations fail to recover. The >1,000 studies of the causes of heat-induced
      bleaching have focused overwhelmingly on the consequences of damage to algal
      photosynthetic processes, and the prevailing model for bleaching invokes a light
      dependent generation of toxic reactive oxygen species (ROS) by heat-damaged
      chloroplasts as the primary trigger. However, the precise mechanisms of bleaching
      remain unknown, and there is evidence for involvement of multiple cellular
      processes. In this study, we asked the simple question of whether bleaching can
      be triggered by heat in the dark, in the absence of photosynthetically derived
      ROS. We used both the sea anemone model system Aiptasia and several species of
      reef-building corals to demonstrate that symbiont loss can occur rapidly during
      heat stress in complete darkness. Furthermore, we observed damage to the
      photosynthetic apparatus under these conditions in both Aiptasia endosymbionts
      and cultured Symbiodinium. These results do not directly contradict the view that
      light-stimulated ROS production is important in bleaching, but they do show that
      there must be another pathway leading to bleaching. Elucidation of this pathway
      should help to clarify bleaching mechanisms under the more usual conditions of
      heat stress in the light.

PMID- 24012314
TI  - Talin autoinhibition is required for morphogenesis.
AB  - The establishment of a multicellular body plan requires coordinating changes in
      cell adhesion and the cytoskeleton to ensure proper cell shape and position
      within a tissue. Cell adhesion to the extracellular matrix (ECM) via integrins
      plays diverse, essential roles during animal embryogenesis and therefore must be
      precisely regulated. Talin, a FERM-domain containing protein, forms a direct link
      between integrin adhesion receptors and the actin cytoskeleton and is an
      important regulator of integrin function. Similar to other FERM proteins, talin
      makes an intramolecular interaction that could autoinhibit its activity. However,
      the functional consequence of such an interaction has not been previously
      explored in vivo. Here, we demonstrate that targeted disruption of talin
      autoinhibition gives rise to morphogenetic defects during fly development and
      specifically that dorsal closure (DC), a process that resembles wound healing, is
      delayed. Impairment of autoinhibition leads to reduced talin turnover at and
      increased talin and integrin recruitment to sites of integrin-ECM attachment.
      Finally, we present evidence that talin autoinhibition is regulated by Rap1
      dependent signaling. Based on our data, we propose that talin autoinhibition
      provides a switch for modulating adhesion turnover and adhesion stability that is
      essential for morphogenesis.

PMID- 24012313
TI  - Paratrypanosoma is a novel early-branching trypanosomatid.
AB  - The kinetoplastids are a widespread and important group of single-celled
      eukaryotes, many of which are devastating parasites of animals, including humans.
      We have discovered a new insect trypanosomatid in the gut of Culex pipiens
      mosquitoes. Glyceraldehyde-3-phosphate dehydrogenase- and SSU rRNA-based
      phylogenetic analyses show this parasite to constitute a distinct branch between
      the free-living Bodo saltans and the obligatory parasitic clades represented by
      the genus Trypanosoma and other trypanosomatids. From draft genome sequence data,
      we identified 114 protein genes shared among the new flagellate, 15
      trypanosomatid species, B. saltans, and the heterolobosean Naegleria gruberi, as
      well as 129 protein genes shared with the basal kinetoplastid Perkinsela sp.
      Individual protein phylogenies together with analyses of concatenated alignments
      show that the new species, here named Paratrypanosoma confusum n. gen., n. sp.,
      branches with very high support at the base of the family Trypanosomatidae. P.
      confusum thus represents a long-sought-after missing link between the ancestral
      free-living bodonids and the derived parasitic trypanosomatids. Further analysis
      of the P. confusum genome should provide insight into the emergence of parasitism
      in the medically important trypanosomatids.

PMID- 24012315
TI  - Active segregation of yeast mitochondria by Myo2 is essential and mediated by
      Mmr1 and Ypt11.
AB  - Active segregation of essential organelles is required for successful cell
      division. The essential budding yeast myosin V Myo2 actively segregates most
      organelles along polarized actin cables. The mechanism of mitochondrial
      segregation remains controversial, with movement driven by actin polymerization,
      movement driven by association with transported cortical endoplasmic reticulum
      (ER), and direct transport by Myo2 proposed as models. Two nonessential proteins,
      Mmr1 and the Rab GTPase Ypt11, bind Myo2 and have been implicated in
      mitochondrial inheritance, although their specific roles are also contended. We
      generated myo2(sens) mutations that exhibit no overt phenotype but render MMR1
      essential and have compromised Ypt11 binding. We then isolated myo2(sens)mmr1(ts)
      conditional mutants and determined that they have a specific and severe defect in
      active mitochondrial inheritance, revealing mitochondrial transport by Myo2 as an
      essential function. ypt11Delta mmr1(ts) cells also have conditional defects in
      growth and active transport of mitochondria into the bud, both of which are
      suppressed by artificially forcing mitochondrial inheritance. At the restrictive
      temperature, cells defective in mitochondrial inheritance give rise to dead buds
      that go through cytokinesis normally, showing no evidence of a proposed cell
      cycle mitochondrial inheritance checkpoint. Thus, active mitochondrial
      inheritance is an essential process and a function of Myo2 that requires either
      Mmr1 or Ypt11.

PMID- 24012316
TI  - Hippocampus-dependent strengthening of targeted memories via reactivation during
      sleep in humans.
AB  - Recent accumulating evidence in animals and humans has shown that memory
      strengthening occurs, at least partially, during sleep and relies on the covert
      reactivation of individual memory episodes. However, it remains to be determined
      whether the hippocampus critically promotes memory consolidation via the
      reactivation of individual memories during sleep. To investigate the hippocampal
      dependent nature of this phenomenon in humans, we selected two groups of chronic
      temporal lobe epileptic (TLE) patients with selective unilateral (TLE+UHS) or
      bilateral (TLE+BHS) hippocampal sclerosis and a group of matched healthy
      controls, and we requested them to learn the association of sounds cueing the
      appearance of words. On the basis of other similar behavioral paradigms in
      healthy populations, sounds that cued only half of the learned memories were
      presented again during the slow-wave sleep stage (SWS) at night, thus promoting
      memory reactivation of a select set of encoded episodes. A memory test
      administered on the subsequent day showed that the strengthening of reactivated
      memories was observed only in the control subjects and TLE+UHS patients.
      Importantly, the amount of memory strengthening was predicted by the volume of
      spared hippocampus. Thus, the greater the structural integrity of the
      hippocampus, the higher the degree of memory benefit driven by memory
      reactivation. Finally, sleep-specific neurophysiological responses, such as
      spindles and slow waves, differed between the sample groups, and the spindle
      density during SWS predicted the degree of memory benefit observed on day 2.
      Taken together, these findings demonstrate that the hippocampus plays a crucial
      role in the consolidation of memories via covert reactivation during sleep.

PMID- 24012317
TI  - Serum response factor-mediated gene regulation in a Drosophila visual working
      memory.
AB  - BACKGROUND: Navigation through the environment requires a working memory for the
      chosen target and path integration facilitating an approach when the target
      becomes temporarily hidden. We have previously shown that this visual orientation
      memory resides in the ellipsoid body, which is part of the central complex in the
      Drosophila brain. Former analysis of foraging and ignorant mutants have revealed
      that a hierarchical PKG and RSKII kinase signaling cascade in a subset of the
      ellipsoid-body ring neurons is required for this type of working memory in flies.
      RESULTS: Here we show that mutants in the ellipsoid body open (ebo) gene, which
      encodes the actin-binding protein Exportin 6, exhibit excessive nuclear
      accumulation of actin during development and in the adult brain. ebo mutants lack
      the orientation memory independent of the structural defect in the ellipsoid-body
      neuropil, and EBO activity in any type of adult ring neurons is sufficient for
      orientation-memory function. Moreover, genetic interaction studies revealed that
      nuclear actin accumulation in ebo mutants inhibits the Drosophila coactivator
      myocardin-related transcription factor A (dMRTF) and therefore the
      transcriptional activator serum response factor (dSRF). dSRF also functions in
      different ring neurons, suggesting that it regulates abundance of a diffusible
      factor that enables a working memory in ellipsoid-body ring neurons. CONCLUSIONS:
      To date, SRF has only been implicated in longer forms of memory formation like
      synaptic long-term potentiation and depression. This study provides the first
      evidence that SRF-mediated gene regulation is also required for a working memory
      that lasts only for a few seconds.

PMID- 24012318
TI  - Prevention of travellers' diarrhoea: where and who?

PMID- 24012319
TI  - Effectiveness of rifaximin in prevention of diarrhoea in individuals travelling
      to south and southeast Asia: a randomised, double-blind, placebo-controlled,
      phase 3 trial.
AB  - BACKGROUND: Travellers' diarrhoea causes substantial acute and long-term
      morbidity. Chemoprophylaxis with fluoroquinolones or rifaximin is effective in
      prevention of diarrhoea in individuals travelling to Latin America and Africa.
      Little evidence is available to support the protective effect of antimicrobial
      drugs in south and southeast Asia, where enteroinvasive and antibiotic-resistant
      bacteria cause a substantial proportion of diarrhoeal episodes. We aimed to
      assess the effectiveness of rifaximin in prevention of diarrhoea in individuals
      travelling to south and southeast Asia. METHODS: We did this double-blind,
      placebo-controlled, single-centre, parallel-group, clinical trial in Tubingen,
      Germany, between Nov 12, 2009, and Sept 3, 2012. Individuals aged 18-64 years who
      were planning a 6-28 day journey to south and southeast Asia were randomly
      assigned (1:1), according to a randomisation list (permuted block size of eight)
      generated by an independent statistician, to receive placebo or rifaximin 200 mg
      tablets twice daily. All members of the study team, including investigators,
      those assessing outcomes, and data analysts, were masked to treatment allocation.
      The primary endpoint was time to the first episode of classic travellers'
      diarrhoea, defined as three or more loose stools in 24 h, accompanied by one or
      more enteric symptoms. Analyses were by intention to treat and per protocol.
      FINDINGS: We randomly assigned 258 participants to rifaximin (n=129) or placebo
      (n=129), of whom 239 (93%) returned a completed diary and were included in the
      primary effectiveness analysis. 48 (41%) of 117 participants in the placebo group
      and 30 (25%) of 122 in the rifaximin group reported classic episodes of
      travellers' diarrhoea. From departure to 7 days after return, rifaximin provided
      48% protection (95% CI 16-68) by lowering the incidence of travellers' diarrhoea
      from 1.99 (1.50-2.64) per 100 person-days in the placebo group to 1.04 (0.72
      1.48) in the intervention group (incidence rate ratio 0.52, 95% CI 0.32-0.84;
      p=0.005). The number needed to treat was 5.70 (95% CI 3.44-16.69) to prevent one
      case of classic travellers' diarrhoea during the first 3 weeks of follow-up. The
      per-protocol analysis essentially corroborated the findings from the intention-to
      treat analysis. We recorded one serious adverse event in a participant in the
      rifaximin group who had grade 3 right lower quadrant abdominal pain 72 h after
      the last intake of study drug. The complaints were considered unlikely to be
      related to use of the drug. INTERPRETATION: Rifaximin is moderately effective in
      prevention of diarrhoea in individuals travelling to south and southeast Asia.
      Similar studies are needed to inform travellers and practitioners about the
      effectiveness of this drug at other popular destinations.

PMID- 24012321
TI  - Sorption capacity of plastic debris for hydrophobic organic chemicals.
AB  - The occurrence of microplastics (MPs) in the ocean is an emerging world-wide
      concern. Due to high sorption capacity of plastics for hydrophobic organic
      chemicals (HOCs), sorption may play an important role in the transport processes
      of HOCs. However, sorption capacity of various plastic materials is rarely
      documented except in the case of those used for environmental sampling purposes.
      In this study, we measured partition coefficients between MPs and seawater
      (KMPsw) for 8 polycyclic aromatic hydrocarbons (PAHs), 4 hexachlorocyclohexanes
      (HCHs) and 2 chlorinated benzenes (CBs). Three surrogate polymers - polyethylene,
      polypropylene, and polystyrene - were used as model plastic debris because they
      are the major components of microplastic debris found. Due to the limited
      solubility of HOCs in seawater and their long equilibration time, a third-phase
      partitioning method was used for the determination of KMPsw. First, partition
      coefficients between polydimethylsiloxane (PDMS) and seawater (KPDMSsw) were
      measured. For the determination of KMPsw, the distribution of HOCs between PDMS
      or plastics and solvent mixture (methanol:water=8:2 (v/v)) was determined after
      apparent equilibrium up to 12 weeks. Plastic debris was prepared in a laboratory
      by physical crushing; the median longest dimension was 320-440 MUm. Partition
      coefficients between polyethylene and seawater obtained using the third-phase
      equilibrium method agreed well with experimental partition coefficients between
      low-density polyethylene and water in the literature. The values of KMPsw were
      generally in the order of polystyrene, polyethylene, and polypropylene for most
      of the chemicals tested. The ranges of log KMPsw were 2.04-7.87, 2.18-7.00, and
      2.63-7.52 for polyethylene, polypropylene, and polystyrene, respectively. The
      partition coefficients of plastic debris can be as high as other frequently used
      partition coefficients, such as 1-octanol-water partition coefficients (Kow) and
      log KMPsw showed good linear correlations with log Kow. High sorption capacity of
      microplastics implies the importance of MP-associated transport of HOCs in the
      marine environment.

PMID- 24012322
TI  - The alteration of spontaneous low frequency oscillations caused by acute
      electromagnetic fields exposure.
AB  - OBJECTIVE: The motivation of this study is to evaluate the possible alteration of
      regional resting state brain activity induced by the acute radiofrequency
      electromagnetic field (RF-EMF) exposure (30min) of Long Term Evolution (LTE)
      signal. METHODS: We designed a controllable near-field LTE RF-EMF exposure
      environment. Eighteen subjects participated in a double-blind, crossover,
      randomized and counterbalanced experiment including two sessions (real and sham
      exposure). The radiation source was close to the right ear. Then the resting
      state fMRI signals of human brain were collected before and after the exposure in
      both sessions. We measured the amplitude of low frequency fluctuation (ALFF) and
      fractional ALFF (fALFF) to characterize the spontaneous brain activity. RESULTS:
      We found the decreased ALFF value around in left superior temporal gyrus, left
      middle temporal gyrus, right superior temporal gyrus, right medial frontal gyrus
      and right paracentral lobule after the real exposure. And the decreased fALFF
      value was also detected in right medial frontal gyrus and right paracentral
      lobule. CONCLUSIONS: The study provided the evidences that 30min LTE RF-EMF
      exposure modulated the spontaneous low frequency fluctuations in some brain
      regions. SIGNIFICANCE: With resting state fMRI, we found the alteration of
      spontaneous low frequency fluctuations induced by the acute LTE RF-EMF exposure.

PMID- 24012323
TI  - Determinants of marital behaviour in five Apennine communities of Central Italy
      inferred by surname analysis, repeated pairs and kinship estimates.
AB  - The work makes use of surname analysis, repeated pairs and kinship estimates in
      11,009 marriage records celebrated in five communities of the Italian Central
      Apennine (Celano, Lecce dei Marsi, Ortucchio, Roio, Villavallelonga) from 1802 to
      1965 with the objective to deepen knowledge of the relative influence of several
      determinants on their marital behaviour. These towns are part of the same
      geographic and economic environment: the slopes of the ancient Fucino Lake. This
      work further elaborates the results from previous studies on the bio-demographic
      model of the region. The data were analyzed according to three periods of
      approximately 50 years. Results show the highest inbreeding coefficients in the
      pastoral towns of Roio and Villavallelonga. Repeated pair analysis highlights a
      certain degree of population subdivision which declined in time in Celano, Lecce
      dei Marsi and Ortucchio. The highest and increasing values of RP-RPr in time in
      Roio suggest a general reduction in genetic heterogeneity. This is possibly due
      to the celebration of marriages among families selected on the economic basis of
      pastoralism, as this town historically has had a leading tradition of sheep
      farming. Villavallelonga, excluding isonymous marriages, shows an increase in
      repeated pair unions in time, thus revealing a substructure with marriages among
      preferred lineages. This is in line with previous results on consanguineous
      marriages which indicated the tendency of avoiding unions between close relatives
      in this small geographic isolate. This study demonstrates the influence of
      geographical (altitude) and social factors (pastoralism) on the marital
      structures of the investigated populations. 

PMID- 24012324
TI  - Plasmapheresis as treatment for hyperlipidemic pancreatitis.
AB  - BACKGROUND: Severe hypertriglyceridemia with an accumulation of chylomicrons and
      triglyceride figures >1000 mg/dL can cause acute pancreatitis, a potentially
      fatal complication. The option of rapid reduction in triglyceride concentrations
      is attractive and possible with plasmapheresis. METHODS: We present the results
      of an analysis of 11 patients admitted to the intensive care unit with severe
      hypertriglyceridemic pancreatitis and treated with plasmapheresis. The procedure
      was repeated until serum triglycerides were below 1000 mg/dL. We recorded
      anthropometric, clinical data as well as final outcome. RESULTS: In eight
      patients a single plasma exchange was sufficient to reduce triglyceride figures
      <1000 mg/dL. Only three patients died, all with the worst severity indexes and
      who experienced the longest delay before the procedure. CONCLUSIONS: Our results,
      together with a review of the literature, confirm the need for a randomized
      clinical trial to compare conventional treatment vs. plasmapheresis in patients
      with severe hypertriglyceridemic pancreatitis.

PMID- 24012325
TI  - Ultrasonography analysis of gallbladder motility in patients with functional
      dyspepsia.
AB  - BACKGROUND: Gallbladder motility has been studied in patients with functional
      gastrointestinal disorders, such as functional dyspepsia, irritable bowel
      syndrome and biliary disorders without gallstones and results of these
      observations are often inconclusive and conflicting. METHODS: The investigation
      was performed on 180 therapy-naive newly diagnosed patients with functional
      dyspepsia (97 females and 83 males), aged 20-79 in which we have investigate
      ultrasonographically parameters of gallbladder motility. RESULTS: Bonferroni post
      hoc correction stressed that fasting gallbladder volume and ejection fraction
      were significantly distorted in individuals with postprandial distress syndrome,
      although, the residual gallbladder volume was significantly lower in patients
      with epigastric pain syndrome comparing with other examinees. Ejection fraction
      of the gallbladder negatively correlated with body mass index. CONCLUSION: The
      impaired contractibility of the gall bladder in patients with functional
      dyspepsia, based on the results of this study, is illustrated by the changes in
      the ejection fraction, which was more pronounced in patients with the
      postprandial distress syndrome.

PMID- 24012326
TI  - Progress update: fluid and imaging biomarkers in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a growing health crisis around the world. Although
      significant progress has been made in our understanding of AD pathogenesis, there
      is currently no effective treatment to delay onset or prevent the disease. The
      focus has now shifted to the identification and treatment of AD in the early
      clinical stages as well as before cognitive symptoms emerge-during the long
      preclinical stage. It is possible that diagnosis of individuals with AD will be
      more accurate when clinical symptoms and signs are combined with biomarkers,
      which can improve both the diagnostic and prognostic accuracy of AD and its
      differentiation from the other neurodegenerative diseases. This review discusses
      fluid and imaging biomarkers that have shown promise in such areas, as well as
      some of the current challenges that face the field. 

PMID- 24012328
TI  - Striatal-enriched protein tyrosine phosphatase-STEPs toward understanding chronic
      stress-induced activation of corticotrophin releasing factor neurons in the rat
      bed nucleus of the stria terminalis.
AB  - BACKGROUND: Striatal-enriched protein tyrosine phosphatase (STEP) is a brain
      specific protein tyrosine phosphatase that opposes the development of synaptic
      strengthening and the consolidation of fear memories. In contrast, stress
      facilitates fear memory formation, potentially by activating corticotrophin
      releasing factor (CRF) neurons in the anterolateral cell group of the bed nucleus
      of the stria terminalis (BNSTALG). METHODS: Here, using dual-immunofluorescence,
      single-cell reverse transcriptase polymerase chain reaction, quantitative reverse
      transcriptase polymerase chain reaction, Western blot, and whole-cell patch-clamp
      electrophysiology, we examined the expression and role of STEP in regulating
      synaptic plasticity in rat BNSTALG neurons and its modulation by stress. RESULTS:
      Striatal-enriched protein tyrosine phosphatase was selectively expressed in CRF
      neurons in the oval nucleus of the BNSTALG. Following repeated restraint stress
      (RRS), animals displayed a significant increase in anxiety-like behavior, which
      was associated with a downregulation of STEP messenger RNA and protein expression
      in the BNSTALG, as well as selectively enhancing the magnitude of long-term
      potentiation (LTP) induced in Type III, putative CRF neurons. To determine if the
      changes in STEP expression following RRS were mechanistically related to LTP
      facilitation, we examined the effects of intracellular application of STEP on the
      induction of LTP. STEP completely blocked the RRS-induced facilitation of LTP in
      BNSTALG neurons. CONCLUSIONS: Hence, STEP acts to buffer CRF neurons against
      excessive activation, while downregulation of STEP after chronic stress may
      result in pathologic activation of CRF neurons in the BNSTALG and contribute to
      prolonged states of anxiety. Thus, targeted manipulations of STEP activity might
      represent a novel treatment strategy for stress-induced anxiety disorders.

PMID- 24012327
TI  - Selective, retrieval-independent disruption of methamphetamine-associated memory
      by actin depolymerization.
AB  - BACKGROUND: Memories associated with drugs of abuse, such as methamphetamine
      (METH), increase relapse vulnerability to substance use disorder. There is a
      growing consensus that memory is supported by structural and functional
      plasticity driven by F-actin polymerization in postsynaptic dendritic spines at
      excitatory synapses. However, the mechanisms responsible for the long-term
      maintenance of memories, after consolidation has occurred, are largely unknown.
      METHODS: Conditioned place preference (n = 112) and context-induced reinstatement
      of self-administration (n = 19) were used to assess the role of F-actin
      polymerization and myosin II, a molecular motor that drives memory-promoting
      dendritic spine actin polymerization, in the maintenance of METH-associated
      memories and related structural plasticity. RESULTS: Memories formed through
      association with METH but not associations with foot shock or food reward were
      disrupted by a highly-specific actin cycling inhibitor when infused into the
      amygdala during the postconsolidation maintenance phase. This selective effect of
      depolymerization on METH-associated memory was immediate, persistent, and did not
      depend upon retrieval or strength of the association. Inhibition of non-muscle
      myosin II also resulted in a disruption of METH-associated memory. CONCLUSIONS:
      Thus, drug-associated memories seem to be actively maintained by a unique form of
      cycling F-actin driven by myosin II. This finding provides a potential
      therapeutic approach for the selective treatment of unwanted memories associated
      with psychiatric disorders that is both selective and does not rely on retrieval
      of the memory. The results further suggest that memory maintenance depends upon
      the preservation of polymerized actin.

PMID- 24012329
TI  - Clinical features of spontaneous coronary artery dissection.
AB  - BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an infrequent but
      increasingly recognized cause of acute coronary syndrome (ACS). Previous case
      reports demonstrated that this condition occurs in young females with a low
      atherosclerotic risk factor burden and may be associated with peripartum or
      postpartum status. The purpose of this study was to review patients with
      angiographically confirmed SCAD to provide additional insight into the diagnosis
      and treatment of this condition. METHODS AND RESULTS: We screened medical records
      of all patients with ACS from March 2001 to November 2012. From these patients,
      we selected patients with SCAD based on coronary angiographic review. Of a total
      of 1159 ACS patients, 10 patients (0.86%) were diagnosed with SCAD. The mean age
      of these patients was 46 years, and 9 were female. ST-elevation myocardial
      infarction (STEMI) was observed in 9 patients and 5 patients had no coronary risk
      factors. One patient was treated conservatively with medication alone and 3
      patients underwent thrombectomy. Balloon angioplasty was performed in 2 patients,
      and a bare metal stent was placed in one of these patients later. In the
      remaining 4 patients, bare metal stents were implanted emergently. Follow-up
      coronary angiography showed appropriate repair of SCAD in all 10 patients.
      CONCLUSIONS: In our experience, the clinical features of SCAD appear to be
      similar to those reported previously. SCAD appears to be rare, but it should be
      considered in ACS patients, especially in younger females.

PMID- 24012330
TI  - Rationale and design of J-ACCESS 4: prognostic impact of reducing myocardial
      ischemia identified using ECG-gated myocardial perfusion SPECT in Japanese
      patients with coronary artery disease.
AB  - BACKGROUND: The findings of our recent study entitled, "Japanese Assessment of
      Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS)" showed
      that myocardial perfusion single photon emission computed tomography (MPS) can
      detect coronary artery disease (CAD) and help to predict future cardiac events in
      patients with suspected or extant CAD. However, the extent of the benefit
      conferred by percutaneous coronary intervention (PCI) as an initial management
      strategy compared with optimal medical therapy remains controversial. Little
      evidence supports the notion that myocardial ischemia identified using MPS is an
      alternative target of coronary revascularization to reduce the likelihood of
      developing cardiac events. METHODS: The multicenter, prospective cohort J-ACCESS
      4 study aims to clarify the prognostic impact of reducing myocardial ischemia
      determined using electrocardiogram-gated MPS in Japanese patients with coronary
      artery disease. We started to register patients in J-ACCESS 4 at 74 facilities
      during June 2012 and will continue to do so until December 2013 or until the
      cohort comprises 500 patients who will participate in the study from one month
      before, until two months after stress/rest MPS assessment. Imaging data, the
      background of the patients including coronary risk factors and treatment before
      MPS assessments will be analyzed. The patients will undergo coronary
      revascularization within two months after MPS and/or receive appropriate medical
      therapy. The second stress/rest MPS will be performed from 4 to 10 months after
      coronary revascularization or registration. They will be followed up for over one
      year after the second MPS assessment. The primary endpoints will be cardiac
      death, sudden death of unknown cause, non-fatal myocardial infarction, and
      hospitalization for heart failure. The secondary endpoints will comprise death
      due to all causes including non-cardiac death and any cardiovascular events. This
      study will be completed in 2015. Here, we describe the design of the J-ACCESS 4
      study.

PMID- 24012331
TI  - Plateletcrit and red cell distribution width are independent predictors of the
      slow coronary flow phenomenon.
AB  - BACKGROUND AND PURPOSE: Endothelial dysfunction may play a role in the
      pathogenesis of the slow coronary flow (SCF) phenomenon. A detailed examination
      of blood cellular components has not been performed for this condition. We
      investigated the relationship between SCF and whole blood cell counts. METHOD:
      Records of 17,315 patients who underwent coronary angiography between January
      2006 and December 2012 were evaluated retrospectively. A total of 146 patients
      with SCF were compared with 148 patients with normal coronary arteries according
      to demographic data, complete blood count, and biochemical parameters. RESULTS:
      The following parameters were significantly higher in SCF patients than in
      patients with normal coronary arteries: percentage of smokers (36.3% vs. 25%,
      p=0.036), body mass index (26.69 +/- 2.84 vs. 26.07 +/- 3.15, p=0.049), white
      blood cells (WBCs) (7.52 +/- 1.43 * 10(3)mm(-3) vs. 7.01 +/- 1.42 * 10(3)mm(-3),
      p=0.002), red cell distribution width (RDW) (13.68 +/- 1.42% vs. 13.15 +/- 1.13%,
      p<0.001), platelets (250.29 +/- 50.96 * 10(3)mm(-3) vs. 226.10 +/- 38.02 *
      10(3)mm(-3), p<0.001), plateletcrit (PCT) (0.214 +/- 0.40% vs. 0.184 +/-0.29%,
      p<0.001), mean platelet volume (8.63 +/- 1.10fL vs. 8.22 +/- 0.83 fL, p<0.001),
      platelet distribution width (PDW) (16.58 +/- 0.76% vs. 16.45 +/- 0.57%, p=0.028),
      and neutrophils (4.44 +/- 1.25 * 10(3)mm(-3) vs. 4.12 +/- 1.24 * 10(3)mm(-3),
      p=0.029). Positive PCT values [odds ratio (OR), 4.165; 95% confidence interval
      (CI), 2.493-6.959; p<0.001) and RDW (OR, 1.304; 95% CI, 1.034-1.645; p=0.025)
      were independent predictors of SCF. CONCLUSION: Although within the normal range,
      the increased numbers of WBCs and neutrophils in patients with SCF suggest that
      SCF may be a subclinical inflammatory condition. Furthermore, increased RDW and
      PDW in SCF patients may cause microvascular blood flow resistance due to impaired
      cell deformability. The PCT provides reliable data regarding total platelet mass
      and may be a useful predictor of SCF.

PMID- 24012332
TI  - Hypocalcemia is related to left ventricular diastolic dysfunction in patients
      with chronic kidney disease.
AB  - BACKGROUND: Left ventricular (LV) diastolic dysfunction in patients with chronic
      kidney disease (CKD) is of a complex nature and is the predominant cause of
      congestive heart failure in this group of patients. This work aimed to evaluate
      the potential effect of disturbances in calcium-phosphorus (Ca-P) metabolism in
      patients with CKD on LV diastolic function as assessed by echocardiography.
      MATERIALS AND METHODS: The study group consisted of 81 ambulatory patients with
      CKD, stages 2-5, with preserved LV systolic function-LV ejection fraction >50%
      and with sinus rhythm. Standard echocardiography was performed in all patients
      with tissue Doppler echocardiography for the evaluation of the systolic velocity
      and both diastolic velocities of LV (EmLV and AmLV). The following laboratory
      parameters were measured: serum creatinine concentration, estimated glomerular
      filtration rate, and the levels of urea, P, Ca, parathormone, platelet count,
      hemoglobin level, and N-terminal pro-B-type natriuretic peptide (NT-proBNP)
      levels. Patients were divided into two groups according to the results of EmLV:
      group with LV diastolic dysfunction (EmLV<8cm/s) DF (+) and group with normal LV
      diastolic function DF (-), when EmLV was >=8cm/s. RESULTS: Patients in DF (+)
      group, as compared to DF (-) patients, manifested a lower serum Ca level and an
      elevated NT-proBNP level [9.03+/-0.76mg/dL vs 9.44+/-0.78mg/dL, p=0.02, and 257.9
      (32.6-12,633)pg/ml vs 149 (11.7-966)pg/ml, p=0.035, respectively]. The area under
      the receiver operating characteristics (ROC) curve of Ca for diastolic
      dysfunction was 0.627, 95% CI (0.511-0.734), p=0.04, whereas ROC derived Ca value
      of <=9.82mg/dL was characterized by a sensitivity of 91.8% and specificity of
      38.1% for diagnosing LV diastolic dysfunction. The only independent variable
      predicting LV diastolic dysfunction as measured by a multivariate logistic
      regression analysis was Ca level<=9.82mg/dL with odds ratio=8.81 (95% CI 1.49
      51.82), p=0.014. CONCLUSIONS: Hypocalcemia is an independent predictive factor
      for LV diastolic dysfunction in patients with CKD.

PMID- 24012333
TI  - Relation between the GRACE score and severity of atherosclerosis in acute
      coronary syndrome.
AB  - BACKGROUND: Patients with non-ST-elevation acute coronary syndrome are
      heterogeneous in terms of clinical presentation and immediate- and long-term risk
      of death or non-fatal ischemic events. The aim of the present study was to
      evaluate the relationship between the Global Registry of Acute Coronary Events
      (GRACE) score and severity of coronary artery disease angiographically evaluated
      by Gensini score in patients with non-ST-elevation acute coronary syndrome.
      METHODS: A total of 245 patients with non-ST-elevation acute coronary syndrome
      were enrolled to the study. Based on the GRACE risk score classification system,
      the patients were divided into low- (n=97, 39.6%), intermediate- (n=84, 34.3%),
      and high- (n=64, 26.1%) risk groups. All patients underwent coronary angiography
      within five days after admission. RESULTS: The Gensini scores were 26+/-29 in the
      low-risk group, 29+/-19 in the intermediate-risk group, and 38+/-23 in the high
      risk group (p=0.016). The low-risk group was significantly different from the
      high-risk group (p=0.013), and the difference from the intermediate-risk group
      almost reached significance. Normal, noncritical, one and two, or multivessel
      disease were identified in 15 (6.1%), 31 (12.7%), 75 (30.6%), and 124 (50.6%)
      patients, respectively. The prevalence of multivessel disease was 28% in the low
      risk group, 30% in the intermediate-risk group, and 42% in the high-risk group.
      The high-risk group was significantly different from the low-risk group (p<0.01).
      CONCLUSION: Our study demonstrates that the GRACE score has significant value for
      assessing the severity and extent of coronary artery stenosis in patients with
      non-ST-elevation acute coronary syndrome.

PMID- 24012334
TI  - Utility of right ventricular Tei-index for assessing disease severity and
      determining response to treatment in patients with pulmonary arterial
      hypertension.
AB  - BACKGROUND: We sought to evaluate the potential utility of echocardiography
      derived morphological and functional right ventricular (RV) variables for
      assessing disease severity of pulmonary arterial hypertension (PAH) and
      determining the changes in the patient's hemodynamics in the clinical course.
      METHODS AND RESULTS: This study consisted of 24 normal controls (the control
      group) and 24 patients with PAH at rest or with exercise (the PAH group) who
      underwent echocardiography, right heart catheterization, plasma brain natriuretic
      peptide (BNP) measurement, and six-minute walk distance (6MWD) test. The PAH
      group had poorer RV echocardiographic variables than the control group. RV Tei
      index was more strongly correlated with 6MWD, BNP, cardiac index, mean pulmonary
      arterial pressure, and pulmonary vascular resistance (PVR) than other RV
      echocardiography-derived variables including RV end-diastolic areas, RV
      fractional area change, and tricuspid annular plane systolic excursion. In 16 of
      the 24 patients who successfully underwent repeated examination during follow up
      (13.3 +/- 4.9 months; range, 5-24 months), PVR decreased from 486 +/- 380 dynes
      cm(-5) to 346 +/- 252 dynes cm(-5), and RV Tei-index decreased from 0.55 +/- 0.30
      to 0.42 +/- 0.17, and the changes in RV Tei-index were correlated with the
      concomitant changes in PVR during the clinical course of PAH (r=0.706, p=0.002).
      Tricuspid annular plane systolic excursion and RV fractional area change did not
      change during the follow up. CONCLUSIONS: Quantitative echocardiography revealed
      that the measurement of RV Tei-index is of great clinical utility for predicting
      disease severity of PAH and determining the changes in the patient's hemodynamics
      in the clinical course.

PMID- 24012336
TI  - Introduction: tumor as an organ.

PMID- 24012335
TI  - Spatial organization of Hippo signaling at the plasma membrane mediated by the
      tumor suppressor Merlin/NF2.
AB  - Although Merlin/NF2 was discovered two decades ago as a tumor suppressor
      underlying Neurofibromatosis type II, its precise molecular mechanism remains
      poorly understood. Recent studies in Drosophila revealed a potential link between
      Merlin and the Hippo pathway by placing Merlin genetically upstream of the kinase
      Hpo/Mst. In contrast to the commonly depicted linear model of Merlin functioning
      through Hpo/Mst, here we show that in both Drosophila and mammals, Merlin
      promotes downstream Hippo signaling without activating the intrinsic kinase
      activity of Hpo/Mst. Instead, Merlin directly binds and recruits the effector
      kinase Wts/Lats to the plasma membrane. Membrane recruitment, in turn, promotes
      Wts phosphorylation by the Hpo-Sav kinase complex. We further show that
      disruption of the actin cytoskeleton promotes Merlin-Wts interactions, which
      implicates Merlin in actin-mediated regulation of Hippo signaling. Our findings
      elucidate an important molecular function of Merlin and highlight the plasma
      membrane as a critical subcellular compartment for Hippo signal transduction.

PMID- 24012337
TI  - Characterization of the stem cell niche and its importance in radiobiological
      response.
AB  - Normal tissues are organized hierarchically with a small number of stem cells,
      able to self-renew and give rise to all the differentiated cells found in the
      respective specialized tissues. The undifferentiated, multipotent state of normal
      stem cells is codetermined by the constituents of a specific anatomical space
      that hosts the normal stem cell population, called the "stem cell niche."
      Radiation interferes not only with the stem cell population but also with the
      stem cell niche, thus modulating a complex regulatory network. There is now
      mounting experimental evidence that many solid cancers share this hierarchical
      organization with their tissue of origin, with the cancer stem cells also
      occupying specialized niches. In this review, we highlight some of the best
      characterized aspects of normal tissue stem cells, cancer stem cells, and their
      niches in the bone marrow, gut, and brain, as well as their responses to ionizing
      radiation.

PMID- 24012339
TI  - The roles of reactive oxygen species and autophagy in mediating the tolerance of
      tumor cells to cycling hypoxia.
AB  - Tumor hypoxia (low oxygenation) causes treatment resistance and poor patient
      outcome. A substantial fraction of tumor cells experience cycling hypoxia,
      characterized by transient episodes of hypoxia and reoxygenation. These cells are
      under a unique burden of stress, mediated by excessive production of reactive
      oxygen species (ROS). Cellular components damaged by ROS can be cleared by
      autophagy, rendering cycling hypoxic tumor cells particularly vulnerable to
      inhibition of autophagy and its upstream regulatory pathways. Activation of the
      PERK-mediated signaling arm of the unfolded protein response during hypoxia plays
      a critical role in the defense against ROS, both by stimulating glutathione
      synthesis pathways and through promoting autophagy.

PMID- 24012340
TI  - Optimization of tumor radiotherapy with modulators of cell metabolism: toward
      clinical applications.
AB  - Most solid tumors are characterized by unstable perfusion patterns, creating
      regions of hypoxia that are detrimental to radiotherapy treatment response.
      Because postsurgical radiotherapy, alone or in combination with other
      interventions, is a first-line treatment for many malignancies, strategies aimed
      at homogeneously increasing tumor pO2 have been the focus of intense research
      over the past decades. Among other approaches of demonstrable clinical and
      preclinical utility, this review focuses on those directly targeting oxygen
      consumption to redirect oxygen from a metabolic fate to the stabilization of
      radiation-induced DNA damage, more particularly drugs targeting glucose and
      lactate metabolism, nitric oxide donors or inducers, and mitogen-activated
      protein kinase pathway inhibitors. Their utility as adjuvant treatments with
      radiotherapy has been proven preclinically, which should foster further their
      clinical development and evaluation.

PMID- 24012338
TI  - Tumors as organs: biologically augmenting radiation therapy by inhibiting
      transforming growth factor beta activity in carcinomas.
AB  - Transforming growth factor beta (TGFbeta) plays critical roles in regulating a
      plethora of physiological processes in normal organs, including morphogenesis,
      embryonic development, stem cell differentiation, immune regulation, and wound
      healing. Though considered a tumor suppressor, TGFbeta is a critical mediator of
      tumor microenvironment, in which it likewise mediates tumor and stromal cell
      phenotype, recruitment, inflammation, immune function, and angiogenesis. The fact
      that activation of TGFbeta is an early and persistent event in irradiated tissues
      and that TGFbeta signaling controls effective DNA damage response provides a new
      means to manipulate tumor response to radiation. Here we discuss preclinical
      studies unraveling TGFbeta effects in cancer treatment and review TGFbeta biology
      in lung cancer as an example of the opportunities for TGFbeta pathway inhibition
      as a pharmaceutical approach to augment radiation therapy.

PMID- 24012341
TI  - Radiation as an immune modulator.
AB  - Radiation therapy is currently one of the most widely utilized treatment
      strategies in the clinical management of cancer. Classically, radiation therapy
      was developed as an anticancer treatment on the basis of its capacity to induce
      DNA double strand breaks in exposed cancer cells, ultimately resulting in tumor
      cell death. Recently, our understanding of radiation effects has expanded widely
      in terms of the consequences of radiation-induced tumor cell death and the
      pertinent cells, signaling pathways, and molecular sensors that modify the tumor
      response to radiation. It is now well accepted that inflammation plays a complex
      dual role in promoting or inhibiting tumor growth. The capacity of inflammatory
      responses to alter the tumor response to radiation therapy, and vice versa, is
      now the subject of intense scientific and clinical investigation. Herein, we
      review the concepts regarding the immunostimulatory properties of radiation
      therapy with particular focus on the effects of radiation therapy on the tumor
      microenvironment.

PMID- 24012342
TI  - Inhibiting vasculogenesis after radiation: a new paradigm to improve local
      control by radiotherapy.
AB  - Tumors are supported by blood vessels, and it has long been debated whether their
      response to irradiation is affected by radiation damage to the vasculature. We
      have shown in preclinical models that, indeed, radiation is damaging to the tumor
      vasculature and strongly inhibits tumor angiogenesis. However, the vasculature
      can recover by colonization from circulating cells, primarily proangiogenenic
      CD11b+ monocytes or macrophages from the bone marrow. This secondary pathway of
      blood vessel formation, known as vasculogenesis, thus acts to restore the tumor
      vasculature and allows the tumor to recur following radiation. The stimulus for
      the influx of these CD11b+ cells into tumors following irradiation is the
      increased levels of hypoxia-inducible factor-1 in the tumor due to induced tumor
      hypoxia secondary to blood vessel loss. This increases tumor levels of the
      chemokine stromal cell-derived factor-1, which has chemokine receptors CXCR4 and
      CXCR7 on monocytes and endothelial cells thereby capturing these cells in the
      tumors. The increase in CD11b+ monocytes in tumors following irradiation can be
      prevented using antibodies or small molecules that inhibit hypoxia-inducible
      factor-1 or the interaction of stromal cell-derived factor-1 with its receptors.
      We show that the effect of inhibiting these chemokine-chemokine receptor
      interactions is a marked increase in the radiation response of transplanted or
      chemically induced tumors in mice and rats. This strategy of inhibiting
      vasculogenesis following tumor irradiation is a new paradigm in radiotherapy and
      suggests that higher levels of local control of tumors in several sites would be
      achievable with this strategy.

PMID- 24012344
TI  - Understanding the tumor microenvironment and radioresistance by combining
      functional imaging with global gene expression.
AB  - The objective of this review is to present an argument for performing joint
      analyses between functional imaging with global gene expression studies. The
      reason for making this link is that tumor microenvironmental influences on
      functional imaging can be uncovered. Such knowledge can lead to (1) more informed
      decisions regarding how to use functional imaging to guide therapy and (2)
      discovery of new therapeutic targets. As such, this approach could lead to
      identification of patients who need aggressive treatment tailored toward the
      phenotype of their tumor vs those who could be spared treatment that carries risk
      for more normal tissue complications. Only a handful of papers have been
      published on this topic thus far, but all show substantial promise.

PMID- 24012343
TI  - Cell death-stimulated cell proliferation: a tissue regeneration mechanism usurped
      by tumors during radiotherapy.
AB  - The death of all the cancer cells in a tumor is the ultimate goal of cancer
      therapy. Therefore, much of the current effort in cancer research is focused on
      activating cellular machinery that facilitates cell death such as factors
      involved in causing apoptosis. However, recently, a number of studies point to
      some counterintuitive roles for apoptotic caspases in radiation therapy as well
      as in tissue regeneration. It appears that a major function of apoptotic caspases
      is to facilitate tissue regeneration and tumor cell repopulation during cancer
      therapy. Because tumor cell repopulation has been shown to be important for local
      tumor relapse, understanding the molecular mechanisms behind tumor repopulation
      would be important to enhance cancer radiotherapy. In this review, we discuss our
      current knowledge of these potentially paradigm-changing phenomena and mechanisms
      in various organisms and their implications on the development of novel cancer
      therapeutics and strategies.

PMID- 24012346
TI  - Liver auto-immunology: the paradox of autoimmunity in a tolerogenic organ.
AB  - The study of the liver as a lymphoid organ is a growing field fueled by our
      better knowledge of the different component of the immune system and how they
      orchestrate an immune-related response. The liver have highly specialized
      mechanisms of immune tolerance, mainly because is continuously exposed to
      microbial and environmental antigens, and dietary components from the gut.
      Accordingly, the liver contains specialized lymphoid subpopulations acting as
      antigen-presenting cells. Growing evidences show that the liver is also
      associated with obesity-associated diseases because of its immune-related
      capacity to sense metabolic stress induced by nutritional surplus. Finally, the
      liver produces a pletora of neo-antigens being the primary metabolic organ of the
      body. Common immune mechanisms play a key pathogenetic role in most of acute and
      chronic liver diseases and in the rejection of liver allografts. Any
      perturbations of liver-related immune functions have important clinical
      implications. This issue of the Journal of Autoimmunity is focused on the more
      recent advances in our knowledge related to the loss of liver tolerance, a
      paradox for a tolerogenic organ, that leads to overactivation of the innate and
      adaptive immune response and the development of autoimmune liver diseases, such
      as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing
      cholangitis. The invited expert review articles capture the underlying
      immunomolecular mechanisms of the development and progression of autoimmune liver
      diseases, the novel field of the immune-related "liver-gut" axis influences to
      the development of liver autoimmunity, the predominant role of genetic factors,
      and the increasingly effective immuno-therapeutic possibilities. 

PMID- 24012345
TI  - PDCD5 negatively regulates autoimmunity by upregulating FOXP3(+) regulatory T
      cells and suppressing Th17 and Th1 responses.
AB  - Maintenance of FOXP3 protein expression is crucial for differentiation and
      maturation of regulatory T (Treg) cells, which play important roles in immune
      homeostasis and immune tolerance. We demonstrate here that PDCD5 interacts with
      FOXP3, increases acetylation of FOXP3 in synergy with Tip60 and enhances the
      repressive function of FOXP3. In PDCD5 transgenic (PDCD5tg) mice, overexpression
      of PDCD5 enhanced the level of FOXP3 protein and percentage of
      CD4(+)CD25(+)FOXP3(+) cells. Naive CD4(+) T cells from PDCD5tg mice were more
      sensitive to TGF-beta-induced Treg polarization and expansion. These induced
      Tregs retained normal suppressive function in vitro. Severity of experimentally
      induced autoimmune encephalomyelitis (EAE) in PDCD5tg mice was significantly
      reduced relative to that of wild-type mice. The beneficial effect of PDCD5 likely
      resulted from increases of Treg cell frequency, accompanied by a reduction of the
      predominant pathogenic Th17/Th1 response. Activation-induced cell death enhanced
      by PDCD5 was also linked to this process. This is the first report revealing that
      PDCD5 activity in T cells suppresses autoimmunity by modulating Tregs. This study
      suggests that PDCD5 serves as a guardian of immunological functions and that the
      PDCD5-FOXP3-Treg axis may be a therapeutic target for autoimmunity.

PMID- 24012347
TI  - Continuous straw provision reduces prevalence of oesophago-gastric ulcer in pigs
      slaughtered at 170 kg (heavy pigs).
AB  - Adopting a 2 * 2 * 2 factorial design, this study evaluated whether continuous
      straw provision by racks, tail docking and gender (barrows vs. females) have an
      effect on the prevalence of lung lesions and oesophago-gastric ulcer (OGU)
      visually scored at slaughter in 635 Italian heavy pigs (169 +/- 4 kg). The lung
      lesions were very low (72% of pigs with score 0), and were not significantly
      different among the experimental groups. Overall, OGU was diagnosed in 47% of the
      pigs. The consumption of small amounts of straw (70 g/day/pig) represented a
      protective factor against the onset of OGU (OR: 0.27). Barrows were more likely
      than females to have OGU (OR: 1.52), while no significant differences between
      docked and undocked pigs were detected. Nevertheless, the presence of straw acted
      as a protective factor particularly in undocked pigs (OR: 0.16), suggesting that
      in this group the absence of rooting material may have a stronger effect on
      welfare.

PMID- 24012348
TI  - Oxidative stress in mice treated with antileishmanial meglumine antimoniate.
AB  - In order to improve the understanding of the toxicity of pentavalent antimony
      (Sb(V)), we investigated the acute effects of meglumine antimoniate (MA) on the
      oxidative stress in heart, liver, kidney, spleen and brain tissue of mice. Levels
      of lipoperoxidation and protein carbonylation were measured to evaluate the
      oxidative status, whereas superoxide dismutase/catalase activity and glutathione
      levels were recorded to examine the antioxidative status. We observed that MA
      caused significant protein carbonylation in the heart, spleen and brain tissue.
      Increased lipoperoxidation was found in the liver and brain tissue. An imbalance
      between superoxide dismutase and catalase activities could be observed in heart,
      liver, spleen and brain tissue. Our results suggest that MA causes oxidative
      stress in several vital organs of mice. This indicates that the production of
      highly reactive oxygen and nitrogen species induced by MA might be involved in
      some of its toxic adverse effects. 

PMID- 24012349
TI  - The oral microbial community of gingivitis and lumpy jaw in captive macropods.
AB  - Gingivitis and lumpy jaw are diseases of polymicrobial aetiology. Although
      Fusobacterium necrophorum has been associated with these diseases in macropods,
      little is known about other organisms associated with these diseases in this
      animal species. PCR-DGGE analysis revealed the potential pathogens associated
      with gingivitis and lumpy jaw in macropods. PCR-DGGE profile comparison between
      the healthy and disease groups indicated a shift in the oral bacterial community
      structures with similarity coefficients of 48% and 35% for gingivitis and lumpy
      jaw respectively. Moreover, gingivitis was associated with increase in bacterial
      diversity (Shannon index = 2.87; PL curve = 45%) while lumpy jaw resulted in a
      decline in bacterial diversity (Shannon index = 2.47; PL curve = 74%). This study
      suggest that the establishment of gingivitis and lumpy jaw diseases follows the
      ecological plaque hypothesis. This forms the basis for an expanded investigation
      in an epidemiological scale and suggests the need for the appropriate choice of
      antimicrobial agent(s) and for the effective management and control of
      polymicrobial diseases.

PMID- 24012350
TI  - Porcine alpha interferon inhibit Japanese encephalitis virus replication by
      different ISGs in vitro.
AB  - Japanese encephalitis virus (JEV) causes serious zoonosis in South Asia,
      Southeast Asia and other areas. Pigs are an important reservoir for this virus in
      nature. The treatment of JEV infection in pigs is important for controlling the
      prevalence of JEV in humans and economic losses in pig farming. In this study, we
      selected a high activity porcine alpha-interferon to inhibit JEV replication in
      porcine kidney cell lines (PK-15). Alpha interferon exhibited high antiviral
      activity against JEV; the expression of three interferon-stimulated genes (ISGs),
      ISG15, Mx2 and OAS L, increased significantly after interferon treatment.
      Furthermore, we verified the anti-JEV effect of these ISGs by RNAi and
      overexpression. Mx2 and OAS L exhibited strong anti-JEV effects in PK-15 cells.
      Based on these novel results, alpha interferon (IFN-alpha) should be considered
      to be a potential drug against JEV in pigs. 

PMID- 24012351
TI  - Radiolucency in the mandible: a seventeen-year follow-up.

PMID- 24012352
TI  - Discrepancy of coronal morphology between mandibular condyle and fossa is related
      to pathogenesis of anterior disk displacement of the temporomandibular joint.
AB  - OBJECTIVE: To evaluate whether morphological discrepancy between the mandibular
      condyle and fossa of the temporomandibular joint (TMJ) is related to disk
      displacement on magnetic resonance imaging (MRI). STUDY DESIGN: This study
      included 61 patients with unilateral internal derangement based on both MRI and
      clinical examination. Coronal morphologies of the condyle and fossa were divided
      into four groups based on Oberg's classification. According to the coronal
      morphology of the condyle and fossa, all joints were dichotomized into either
      harmonized group or a discrepancy group (e.g., angled condyle and concave fossa).
      The incidence of discrepancy and the relationship of the discrepancy to other
      findings on MRI were statistically evaluated. RESULTS: The discrepancy had a
      significantly higher incidence on the affected side. The discrepancy correlated
      with incidence of disk deformity on the affected side. CONCLUSION: Morphological
      discrepancy between the condyle and fossa is related to development of anterior
      disk displacement in the TMJ.

PMID- 24012353
TI  - Reply to the Letter to the Editor by Hermoso-de-Mendoza (2013).

PMID- 24012354
TI  - Relative associations of cattle movements, local spread, and biosecurity with
      bovine viral diarrhoea virus (BVDV) seropositivity in beef and dairy herds.
AB  - The success of bovine viral diarrhoea virus (BVDV) eradication campaigns can be
      undermined by spread through local transmission pathways and poor farmer
      compliance with biosecurity recommendations. This work combines recent survey
      data with cattle movement data to explore the issues likely to impact on the
      success of BVDV control in Scotland. In this analysis, data from 249 beef suckler
      herds and 185 dairy herds in Scotland were studied retrospectively to determine
      the relative influence of cattle movements, local spread, and biosecurity on BVDV
      seropositivity. Multivariable logistic regression models revealed that cattle
      movement risk factors had approximately 3 times greater explanatory power than
      risk factors for local spread amongst beef suckler herds, but approximately the
      same explanatory power as risk factors for local spread amongst dairy herds.
      These findings are most likely related to differences in cattle husbandry
      practices and suggest that where financial prioritization is required, focusing
      on reducing movement-based risk is likely to be of greatest benefit when applied
      to beef suckler herds. The reported use of biosecurity measures such as
      purchasing cattle from BVDV accredited herds only, performing diagnostic
      screening at the time of sale, implementing isolation periods for purchased
      cattle, and installing double fencing on shared field boundaries had minimal
      impact on the risk of beef or dairy herds being seropositive for BVDV. Only 28%
      of beef farmers and 24% of dairy farmers with seropositive herds recognized that
      their cattle were affected by BVDV and those that did perceive a problem were no
      less likely to sell animals as replacement breeding stock and no more likely to
      implement biosecurity measures against local spread than farmers with no
      perceived problems. In relation to the current legislative framework for BVDV
      control in Scotland, these findings emphasize the importance of requiring
      infected herds take appropriate biosecurity measures to prevent further disease
      transmission and conducting adequate follow-up to ensure that biosecurity
      measures are being implemented correctly in the field. 

PMID- 24012355
TI  - Genetic underpinnings of division of labor in the honeybee (Apis mellifera).
AB  - Honeybees have been studied for centuries, starting with Aristotle, who wrote the
      first book about bee breeding. More than 2000 years later, the honeybee entered
      the genomic era as the first social insect whose genome was sequenced, leading to
      significant insight into the molecular mechanisms underlying social behavior. In
      addition, gene expression studies and knockdown using RNAi have extended the
      understanding of social interactions. Much of the work has focused on caste
      determination - the mechanism that results in reproductive division of labor,
      division of labor within the worker caste, and worker reproduction - an essential
      process underlying eusociality. Here we review the molecular factors involved in
      caste determination and the differential regulation of caste-specific genes.
      Recent findings suggest that division of labor is influenced by a small number of
      loci showing high levels of pleiotropy, suggesting that changes in a small number
      of genes lead to large changes in the phenotype. 

PMID- 24012356
TI  - Community- and farmer-based management of animal African trypanosomosis in
      cattle.
AB  - Tsetse eradication is impossible in many parts of Africa given environmental,
      political, and economic circumstances. Animal African trypanosomosis (AAT)
      control then relies on implementation of local, integrated control strategies by
      communities or farmers that must take into account the eco-epidemiological
      context and the cattle rearing system to be sustainable. 

PMID- 24012357
TI  - Factors associated with Pap smear screening among French women visiting a general
      practitioner in the Rhone-Alpes region.
AB  - BACKGROUND: To help prevent cervical cancer, three yearly opportunistic Pap smear
      screening is recommended in France for women aged 25-65 years. Pap smear
      screening coverage varies with age and socioeconomic level. The aim of this cross
      sectional study was to identify factors associated with a low uptake of Pap smear
      screening among women with no limited access to healthcare. METHODS: We analyzed
      data from women aged 25-65 living in the Rhone-Alpes region who completed a self
      administered questionnaire given to them by general practitioners between June
      and August 2008. The questionnaire covered knowledge about cervical cancer and
      its prevention as well as the women's history of Pap smear screening and other
      health-related behaviors. The relationship between low uptake of Pap smear
      screening--defined as not having had the test within the past 3 years--and a
      range of possible contributing factors was investigated using logistic
      regression. RESULTS: Of 1186 women with an intact uterus who completed the
      questionnaire, 89.1% said they had had a Pap smear within the past 3 years. On
      multivariate analysis, the 10.9% who had not were significantly more likely to
      live alone (1.76 [1.13-2.74]), to have no children (2.17 [1.31-3.62]), to have
      never used contraception (5.35 [2.98-9.62]), to have less knowledge about Pap
      smear screening (3.40 [1.55-7.49]), and to be unvaccinated against hepatitis B
      (0.55 [0.35-0.87]). CONCLUSION: Despite high overall compliance with Pap smear
      screening recommendations among women who consulted general practitioners,
      several factors were significantly associated with a low uptake of the service.
      Considering these factors may help to refine messages aimed at cervical cancer
      prevention.

PMID- 24012358
TI  - The high failure rate of biologic resurfacing of the glenoid in young patients
      with glenohumeral arthritis.
AB  - BACKGROUND: The current study evaluated the outcomes of biologic resurfacing of
      the glenoid using a lateral meniscus allograft or human acellular dermal tissue
      matrix at intermediate-term follow-up. METHODS: Forty-five patients (mean age,
      42.2 years) underwent biologic resurfacing of the glenoid, and 41 were available
      for follow-up at a mean of 2.8 years. Lateral meniscal allograft resurfacing was
      used in 31 patients and human acellular dermal tissue matrix interposition in 10.
      Postoperative range of motion and clinical outcomes were assessed at the final
      follow-up. RESULTS: The overall clinical failure rate was 51.2%. The lateral
      meniscal allograft cohort had a failure rate of 45.2%, with a mean time to
      failure of 3.4 years. Human acellular dermal tissue matrix interposition had a
      failure rate of 70.0%, with a mean time to failure of 2.2 years. Overall,
      significant improvements were seen compared with baseline with respect to the
      visual analog pain score (3.0 vs. 6.3), American Shoulder and Elbow Surgeons
      score (62.0 vs. 36.8), and Simple Shoulder Test score (7.0 vs. 4.0). Significant
      improvements were seen for forward elevation (106 degrees  to 138 degrees ) and
      external rotation (31 degrees  to 51 degrees ). CONCLUSION: Despite significant
      improvements compared with baseline values, biologic resurfacing of the glenoid
      resulted in a high rate of clinical failure at intermediate follow-up. Our
      results suggest that biologic resurfacing of the glenoid may have a minimal and
      as yet undefined role in the management of glenohumeral arthritis in the young
      active patient over more traditional methods of hemiarthroplasty or total
      shoulder arthroplasty.

PMID- 24012359
TI  - Differences in muscle activities during shoulder elevation in patients with
      symptomatic and asymptomatic rotator cuff tears: analysis by positron emission
      tomography.
AB  - BACKGROUND: Differences in muscle activity patterns between patients with
      symptomatic and asymptomatic full-thickness rotator cuff tears have not yet been
      fully clarified. The purpose of this study was to investigate the muscle activity
      pattern by use of positron emission tomography (PET) in patients with symptomatic
      and asymptomatic rotator cuff tears. METHODS: Ten shoulders of 9 patients with
      full-thickness rotator cuff tears were divided into 2 groups by a numerical pain
      rating scale (0-10), symptomatic (>=2) and asymptomatic (0 or 1), with 5
      shoulders each. Scaption exercise of bilateral arms (200 repetitions in 10
      minutes) with a weight of 0.25 kg each was performed before and after injection
      of fluorodeoxyglucose. After PET examination, the standardized uptake value of
      each muscle was calculated to quantify its activity and compared between the two
      groups. RESULTS: The activity of the anterior and middle deltoid was
      significantly decreased in the symptomatic group compared with the asymptomatic
      group (anterior deltoid, P = .02; middle deltoid, P = .03). In contrast, the
      activity of the superior trapezius was significantly increased in the symptomatic
      group compared with the asymptomatic group (P = .02). CONCLUSION: In patients
      with a symptomatic tear, the deltoid activity was decreased and the trapezius
      activity was increased. It is likely that they might have moved the painful
      glenohumeral joint less and instead moved the painless scapulothoracic joint more
      during the prescribed exercise. We conclude that patients with painful rotator
      cuff tears use the parascapular muscles more than those without pain do during
      arm elevation.

PMID- 24012360
TI  - Ultrasound evaluation of arthroscopic full-thickness supraspinatus rotator cuff
      repair: single-row versus double-row suture bridge (transosseous equivalent)
      fixation. Results of a prospective, randomized study.
AB  - BACKGROUND: The purpose of this study was to compare the structural outcomes of a
      single-row rotator cuff repair and double-row suture bridge fixation after
      arthroscopic repair of a full-thickness supraspinatus rotator cuff tear. MATERIAL
      AND METHODS: We evaluated with diagnostic ultrasound a consecutive series of
      ninety shoulders in ninety patients with full-thickness supraspinatus tears at an
      average of 10 months (range, 6-12) after operation. A single surgeon at a single
      hospital performed the repairs. Inclusion criteria were full-thickness
      supraspinatus tears less than 25 mm in their anterior to posterior dimension.
      Exclusion criteria were prior operations on the shoulder, partial thickness
      tears, subscapularis tears, infraspinatus tears, combined supraspinatus and
      infraspinatus repairs and irreparable supraspinatus tears. Forty-three shoulders
      were repaired with single-row technique and 47 shoulders with double-row suture
      bridge technique. Postoperative rehabilitation was identical for both groups.
      Ultrasound criteria for healed repair included visualization of a tendon with
      normal thickness and length, and a negative compression test. RESULTS: Eighty
      three patients were available for ultrasound examination (40 single-row and 43
      suture-bridge). Thirty of 40 patients (75%) with single-row repair demonstrated a
      healed rotator cuff repair compared to 40/43 (93%) patients with suture-bridge
      repair (P = .024). CONCLUSION: Arthroscopic double-row suture bridge repair
      (transosseous equivalent) of an isolated supraspinatus rotator cuff tear resulted
      in a significantly higher tendon healing rate (as determined by ultrasound
      examination) when compared to arthroscopic single-row repair.

PMID- 24012361
TI  - Canal preparation for prosthetic radial head replacement: rasping versus reaming.
AB  - BACKGROUND: While many design-specific features of radial head prostheses have
      been studied (ie, geometry and surface coating), the optimum technique for canal
      preparation has not been determined. We hypothesized that preparation of the
      radial canal with a reamer would allow for the accommodation of a larger stem
      diameter versus following canal preparation with a rasp, and would provide
      acceptable stem-bone micromotion. METHODS: Paired proximal radii from 7 cadavers
      were prepared by a rasp on one side and a reamer on the contralateral side.
      Cementless radial head stems of increasing diameter were sequentially implanted
      up to the maximum size or until a fracture occurred and the micromotion between
      the stem and bone was recorded. RESULTS: In 3 of 5 pairs, at least a 1 mm larger
      stem size fit into the canal after reaming versus after rasping (P = .04). 5 of 7
      radii fractured secondary to intentional stem oversizing. For the optimally-sized
      stems, similar micromotion values were observed whether the canal was rasped (41
      +/- 6 MUm) or reamed (44 +/- 6 MUm) (P = .72). DISCUSSION: This study
      investigated an aspect of radial head arthroplasty technique about which little
      has currently been published. It is possible that use of a reamer rather than a
      rasp, while providing similar initial stability, might expand the stem size
      options for initial press-fit stability, and decrease the risk of fracture.
      CONCLUSION: Radial canal preparation with a reamer allows for implantation of a 1
      mm larger stem diameter versus rasping, while providing comparable initial
      stability to that achieved after rasping.

PMID- 24012362
TI  - Large metaphyseal volume hemiprostheses for complex fractures of the proximal
      humerus.
AB  - BACKGROUND: Results of hemiarthroplasty after acute complex proximal humerus
      fractures are controversial. The main problem is the fixation and healing of the
      greater tuberosity (GT). To address this problem a hemiarthroplasty with a large
      metaphyseal volume was designed and introduced. METHODS: Thirty
      hemiarthroplasties were implanted for acute, complex, proximal humeral fractures
      in 30 consecutive patients (average age: 63.3 years; range, 41-78). One patient
      was lost; 2 patients could only be interviewed telefonically. Two patients had to
      be revised because of secondary displacement of the GT within the first 2
      postoperative years. The remaining 25 patients were assessed clinically,
      radiographically, and with computer tomography (CT) imaging after a mean of 25
      months (range, 24-29). RESULTS: Greater tuberosity healed in situ in 23 patients.
      In 12 cases, CT documented severe resorption of GT without displacement of a
      measurable bone fragment and an intact clinical cuff function with a
      radiographically preserved acromio-humeral distance. The mean Constant score was
      59 points (range, 26-81), the mean relative Constant score 75% (range, 31-100).
      The mean anterior elevation was 117 degrees  (range, 45-160). The mean subjective
      shoulder value was 70% (range, 25-98). In 4 cases (14%), tuberosity dislocation
      occurred which was associated with an increase of fatty infiltration and poor
      result. CONCLUSION: The 2-year results with a large metaphyseal volume fracture
      prosthesis showed good to excellent results, with a failure rate of 14%.
      Substantial resorption of the greater tuberosity was frequent, but was not
      associated with functional incompetence of the rotator cuff. The overall results
      obtained justify its continued use.

PMID- 24012363
TI  - Sinister symbiosis: pathological hematopoietic-stromal interactions in CML.
AB  - The impact of myeloid malignancies on the nonhematopoietic components of the bone
      marrow remains poorly understood. In this issue of Cell Stem Cell, Schepers et
      al. (2013) describe how malignant myeloid cells alter the endosteal hematopoietic
      stem cell (HSC) niche, resulting in the expansion of osteoblastic lineage cells
      that preferentially support malignant HSCs. 

PMID- 24012364
TI  - Breaking the canon: indirect regulation of Wnt signaling in mammary stem cells by
      MMP3.
AB  - Matrix metalloproteases promote tumor cell invasion, epithelial-to-mesenchymal
      transitions, and metastases, but whether they directly regulate stem cells is
      unknown. In this issue of Cell Stem Cell, Kessenbrock et al. (2013) now show that
      MMP3, independent of its proteolytic activity, regulates murine mammary stem
      cells by sequestering noncanonical Wnt signaling ligands, which has implications
      for breast cancer pathogenesis. 

PMID- 24012366
TI  - Broadening the indications for hematopoietic stem cell genetic therapies.
AB  - The use of recombinant retroviral vectors to effect corrective genetic therapies
      in hematopoietic stem cells (HSCs) has long been predicted to revolutionize
      medicine. Two recent papers in Science now show that this technology could be
      considered as effective as, and perhaps superior to, allogeneic HSC transplants
      in some rare diseases. 

PMID- 24012365
TI  - And then there were none: no need for pluripotency factors to induce
      reprogramming.
AB  - While most factors used as reprogramming transgenes can be replaced by other
      means, Oct4 has remained essential until now. Three recent papers have now broken
      this barrier through the use of opposing lineage specifying transgenes and
      chemical modulation, thus signifying a milestone in advancing our understanding
      of pluripotency induction. 

PMID- 24012367
TI  - DNA demethylation in pluripotency and reprogramming: the role of tet proteins and
      cell division.
AB  - Cytosine methylation is found in the genomes of many plants and animals and has
      been associated with transcriptional silencing in mammals. At critical stages in
      embryo development, when cellular potential is reset, DNA methylation is lost in
      a series of "sequential waves." The mechanism underlying this is controversial
      and complex. Several new reports now suggest that TET enzymes and cell division
      are important for these in vivo transitions as well as for experimentally induced
      reprogramming. 

PMID- 24012368
TI  - Chemical approaches to stem cell biology and therapeutics.
AB  - Small molecules that modulate stem cell fate and function offer significant
      opportunities that will allow the full realization of the therapeutic potential
      of stem cells. Rational design and screening for small molecules have identified
      useful compounds to probe fundamental mechanisms of stem cell self-renewal,
      differentiation, and reprogramming and have facilitated the development of cell
      based therapies and therapeutic drugs targeting endogenous stem and progenitor
      cells for repair and regeneration. Here, we will discuss recent scientific and
      therapeutic progress, as well as new perspectives and future challenges for using
      chemical approaches in stem cell biology and regenerative medicine. 

PMID- 24012369
TI  - Architectural niche organization by LHX2 is linked to hair follicle stem cell
      function.
AB  - In adult skin, self-renewing, undifferentiated hair follicle stem cells (HF-SCs)
      reside within a specialized niche, where they spend prolonged times as a single
      layer of polarized, quiescent epithelial cells. When sufficient activating
      signals accumulate, HF-SCs become mobilized to fuel tissue regeneration and hair
      growth. Here, we show that architectural organization of the HF-SC niche by
      transcription factor LHX2 plays a critical role in HF-SC behavior. Using genome
      wide chromatin and transcriptional profiling of HF-SCs in vivo, we show that LHX2
      directly transactivates genes that orchestrate cytoskeletal dynamics and
      adhesion. Conditional ablation of LHX2 results in gross cellular disorganization
      and HF-SC polarization within the niche. LHX2 loss leads to a failure to maintain
      HF-SC quiescence and hair anchoring, as well as progressive transformation of the
      niche into a sebaceous gland. These findings suggest that niche organization
      underlies the requirement for LHX2 in hair follicle structure and function. 

PMID- 24012370
TI  - Substrate envelope-designed potent HIV-1 protease inhibitors to avoid drug
      resistance.
AB  - The rapid evolution of HIV under selective drug pressure has led to multidrug
      resistant (MDR) strains that evade standard therapies. We designed highly potent
      HIV-1 protease inhibitors (PIs) using the substrate envelope model, which
      confines inhibitors within the consensus volume of natural substrates, providing
      inhibitors less susceptible to resistance because a mutation affecting such
      inhibitors will simultaneously affect viral substrate processing. The designed
      PIs share a common chemical scaffold but utilize various moieties that optimally
      fill the substrate envelope, as confirmed by crystal structures. The designed PIs
      retain robust binding to MDR protease variants and display exceptional antiviral
      potencies against different clades of HIV as well as a panel of 12 drug-resistant
      viral strains. The substrate envelope model proves to be a powerful strategy to
      develop potent and robust inhibitors that avoid drug resistance. 

PMID- 24012371
TI  - Structural basis for carbapenemase activity of the OXA-23 beta-lactamase from
      Acinetobacter baumannii.
AB  - Dissemination of Acinetobacter baumannii strains harboring class D beta
      lactamases producing resistance to carbapenem antibiotics severely limits our
      ability to treat deadly Acinetobacter infections. Susceptibility determination in
      the A. baumannii background and kinetic studies with a homogeneous preparation of
      OXA-23 beta-lactamase, the major carbapenemase present in A. baumannii, document
      the ability of this enzyme to manifest resistance to last-resort carbapenem
      antibiotics. We also report three X-ray structures of OXA-23: apo OXA-23 at two
      different pH values, and wild-type OXA-23 in complex with meropenem, a carbapenem
      substrate. The structures and dynamics simulations reveal an important role for
      Leu166, whose motion regulates the access of a hydrolytic water molecule to the
      acyl-enzyme species in imparting carbapenemase activity. 

PMID- 24012372
TI  - Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring
      units (MORTEMUS): a retrospective study.
AB  - BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of
      death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in
      epilepsy monitoring units, providing highly informative data for its still
      elusive pathophysiology. The MORTEMUS study expanded these data through
      comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy
      monitoring units worldwide. METHODS: Between Jan 1, 2008, and Dec 29, 2009, we
      did a systematic retrospective survey of epilepsy monitoring units located in
      Europe, Israel, Australia, and New Zealand, to retrieve data for all
      cardiorespiratory arrests recorded in these units and estimate their incidence.
      Epilepsy monitoring units from other regions were invited to report similar cases
      to further explore the mechanisms. An expert panel reviewed data, including video
      electroencephalogram (VEEG) and electrocardiogram material at the time of
      cardiorespiratory arrests whenever available. FINDINGS: 147 (92%) of 160 units
      responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at
      night), nine near SUDEP, and four deaths from other causes, were reported.
      Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and
      previously unrecognised pattern whereby rapid breathing (18-50 breaths per min)
      developed after secondary generalised tonic-clonic seizure, followed within 3 min
      by transient or terminal cardiorespiratory dysfunction. Where transient, this
      dysfunction later recurred with terminal apnoea occurring within 11 min of the
      end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy
      monitoring units was 5.1 (95% CI 2.6-9.2) per 1000 patient-years, with a risk of
      1.2 (0.6-2.1) per 10,000 VEEG monitorings, probably aggravated by suboptimum
      supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION: SUDEP
      in epilepsy monitoring units primarily follows an early postictal, centrally
      mediated, severe alteration of respiratory and cardiac function induced by
      generalised tonic-clonic seizure, leading to immediate death or a short period of
      partly restored cardiorespiratory function followed by terminal apnoea then
      cardiac arrest. Improved supervision is warranted in epilepsy monitoring units,
      in particular during night time. FUNDING: Commission of European Affairs of the
      International League Against Epilepsy.

PMID- 24012373
TI  - Do preclinical Alzheimer's disease criteria work?

PMID- 24012375
TI  - Reducing the risk of sudden death during epilepsy monitoring.

PMID- 24012374
TI  - Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study.
AB  - BACKGROUND: New research criteria for preclinical Alzheimer's disease have been
      proposed, which include stages for cognitively normal individuals with abnormal
      amyloid markers (stage 1), abnormal amyloid and neuronal injury markers (stage
      2), or abnormal amyloid and neuronal injury markers and subtle cognitive changes
      (stage 3). We aimed to investigate the prevalence and long-term outcome of
      preclinical Alzheimer's disease according to these criteria. METHODS:
      Participants were cognitively normal (clinical dementia rating [CDR]=0) community
      dwelling volunteers aged at least 65 years who were enrolled between 1998 and
      2011 at the Washington University School of Medicine (MO, USA). CSF amyloid-beta1
      42 and tau concentrations and a memory composite score were used to classify
      participants as normal (both markers normal), preclinical Alzheimer's disease
      stage 1-3, or suspected non-Alzheimer pathophysiology (SNAP, abnormal injury
      marker without abnormal amyloid marker). The primary outcome was the proportion
      of participants in each preclinical AD stage. Secondary outcomes included
      progression to CDR at least 0.5, symptomatic Alzheimer's disease (score of at
      least 0.5 for memory and at least one other domain and cognitive impairments
      deemed to be due to Alzheimer's disease), and mortality. We undertook survival
      analyses using subdistribution and standard Cox hazards models and linear mixed
      models. FINDINGS: Of 311 participants, 129 (41%) were classed as normal, 47 (15%)
      as stage 1, 36 (12%) as stage 2, 13 (4%) as stage 3, 72 (23%) as SNAP, and 14
      (5%) remained unclassified. The 5-year progression rate to CDR at least 0.5,
      symptomatic Alzheimer's disease was 2% for participants classed as normal, 11%
      for stage 1, 26% for stage 2, 56% for stage 3, and 5% for SNAP. Compared with
      individuals classed as normal, participants with preclinical Alzheimer's disease
      had an increased risk of death after adjusting for covariates (hazard ratio 6.2,
      95% CI 1.1-35.0; p=0.040). INTERPRETATION: Preclinical Alzheimer's disease is
      common in cognitively normal elderly people and is associated with future
      cognitive decline and mortality. Thus, preclinical Alzheimer's disease could be
      an important target for therapeutic intervention. FUNDING: National Institute of
      Aging of the National Institutes of Health (P01-AG003991, P50-AG05681, P01
      AG02676), Internationale Stichting Alzheimer Onderzoek, the Center for
      Translational Molecular Medicine project LeARN, the EU/EFPIA Innovative Medicines
      Initiative Joint Undertaking, and the Charles and Joanne Knight Alzheimer
      Research Initiative.

PMID- 24012376
TI  - Development of a novel fluorine-18 labeled deuterated fluororasagiline
      ([(18)F]fluororasagiline-D2) radioligand for PET studies of monoamino oxidase B
      (MAO-B).
AB  - The objective of this study was to synthesize and evaluate a novel fluorine-18
      labeled deuterium substituted analogue of rasagiline (9, [(18)F]fluororasagiline
      D2) as a potential PET radioligand for studies of monoamine oxidase B (MAO-B).
      The precursor compound (6) and reference standard (7) were synthesized in multi
      step syntheses. Radiolabeling of 9 was accomplished by a two-step synthesis,
      compromising a nucleophilic substitution followed by hydrolysis of the
      sulfamidate group. The incorporation radiochemical yield from fluorine-18
      fluoride was higher than 30%, the radiochemical purity was >99% and the specific
      radioactivity was >160GBq/MUmol at the time of administration. In vitro compound
      7 inhibited the MAO-B activity with an IC50 of 173.0+/-13.6nM. The MAO-A activity
      was inhibited with an IC50 of 9.9+/-1.1MUM. The fluorine-18 version 9 was
      characterized in the cynomolgus monkey brain where a high brain uptake was found
      (275% SUV at 4min). There was a higher uptake in the striatum and thalamus
      compared to the cortex and cerebellum. A pronounced blocking effect (50%
      decrease) was observed in the specific brain regions after administration of l
      deprenyl (0.5mg/kg) 30min prior to the administration of 9. Radiometabolite
      studies demonstrated 40% of unchanged radioligand at 90min post injection. An
      efficient radiolabeling of 9 was successfully established and in the monkey brain
      9 binds to MAO-B rich regions and its binding is blocked by the selective MAO-B
      compound l-deprenyl. The radioligand 9 is a potential candidate for human PET
      studies. 

PMID- 24012377
TI  - Structural study of the location of the phenyl tail of benzene sulfonamides and
      the effect on human carbonic anhydrase inhibition.
AB  - The crystal structure of 4-phenylacetamidomethyl-benzenesulfonamide (4ITP) bound
      to human carbonic anhydrase (hCA, EC 4.2.1.1) II is reported. 4ITP is a medium
      potency hCA I and II inhibitor (KIs of 54-75nM), a strong mitochondrial CA VA/VB
      inhibitor (KIs of 8.3-8.6nM) and a weak transmembrane CA inhibitor (KIs of 136
      212nM against hCA IX and XII). This elongated compound binds in an extended
      conformation to hCA II, with its tail lying towards the hydrophobic half of the
      active site whereas the sulfonamide moiety coordinates the zinc ion. The present
      structure was compared to that of structurally related aromatic sulfonamides,
      such as 4-phenylacetamido-benzene-sulfonamide (3OYS), 4-(2
      mercaptophenylacetamido)-benzene-sulfonamide (2HD6) and 4-(3-nitrophenyl)-ureido
      benzenesulfonamide (3N2P). Homology models of the hCA I, VA, VB, IX and XII
      structures were build which afforded an understanding of the amino acids involved
      in the binding of these compounds to these isoforms. The main conclusion of the
      study is that the orientation of the tail moiety and the presence of flexible
      linkers as well polar groups in it, strongly influence the potency and the
      selectivity of the sulfonamides for the inhibition of cytosolic, mitochondrial or
      transmembrane CA isoforms. 

PMID- 24012378
TI  - The synthesis and anticancer activity of analogs of the indole phytoalexins
      brassinin, 1-methoxyspirobrassinol methyl ether and cyclobrassinin.
AB  - An effective synthesis of analogs of the indole phytoalexin cyclobrassinin with
      NR1R2 group instead of SCH3 was developed starting from indole-3-carboxaldehyde.
      The target compounds were prepared by spirocyclization of 1-Boc-thioureas with
      the formation of isolable spiroindoline intermediates, followed by the
      trifluoroacetic acid-induced cascade reaction consisting of methanol elimination,
      deprotection and rearrangement of the iminium ion. The structures of novel
      products were elucided by the (1)H and (13)C NMR spectroscopy, including HMBC,
      HSQC, COSY, NOESY and DEPT measurements. Several newly synthesized compounds
      demonstrated significant antiproliferative/cytotoxic activity against human
      leukemia and solid tumor cell lines, as well as remarkable selectivity of these
      effects against cancer cells relative to the non-malignant HUVEC cells. 

PMID- 24012379
TI  - Evaluation of molecular model-based discovery of ecto-5'-nucleotidase inhibitors
      on the basis of X-ray structures.
AB  - The enzyme ecto-5'-nucleotidase (e5NT, CD73), a metallophosphoesterase, is a
      critical component of adenosine metabolism and signaling and implicated in
      different disease states. Therefore, attempts have been made to discover
      inhibitors of e5NT. For example, a virtual screening study using a molecular
      model of the enzyme has led to the identification of a new series of sulfonamide
      containing e5NT inhibitors. The recent availability of several X-ray structures
      of human e5NT in complex with inhibitors has made it possible to re-evaluate this
      model building and virtual screening effort. We have assessed the quality of the
      model in detail and analyzed the question why it was possible to identify a new
      series of inhibitors on the basis of model-based docking calculations. The model
      utilized for virtual screening was found to be topologically correct and approach
      experimental accuracy in the active site region. Two key features within the
      active site were identified as major determinants for the successfully
      identification of inhibitors. Taken together, the results rationalize the
      computer-aided discovery of sulfonamide inhibitors of e5NT and provide further
      support for the use of carefully built protein models for virtual screening. 

PMID- 24012381
TI  - Intermolecular interaction of voriconazole analogues with model membrane by DSC
      and NMR, and their antifungal activity using NMR based metabolic profiling.
AB  - The development of novel antifungal agents with high susceptibility and increased
      potency can be achieved by increasing their overall lipophilicity. To enhance the
      lipophilicity of voriconazole, a second generation azole antifungal agent, we
      have synthesized its carboxylic acid ester analogues, namely p-methoxybenzoate
      (Vpmb), toluate (Vtol), benzoate (Vbz) and p-nitrobenzoate (Vpnb). The
      intermolecular interactions of these analogues with model membrane have been
      investigated using nuclear magnetic resonance (NMR) and differential scanning
      calorimetric (DSC) techniques. The results indicate varying degree of changes in
      the membrane bilayer's structural architecture and physico-chemical
      characteristics which possibly can be correlated with the antifungal effects via
      fungal membrane. Rapid metabolite profiling of chemical entities using cell
      preparations is one of the most important steps in drug discovery. We have
      evaluated the effect of synthesized analogues on Candida albicans. The method
      involves real time (1)H NMR measurement of intact cells monitoring NMR signals
      from fungal metabolites which gives Metabolic End Point (MEP). This is then
      compared with Minimum Inhibitory Concentration (MIC) determined using
      conventional methods. Results indicate that one of the synthesized analogues,
      Vpmb shows reasonably good activity. 

PMID- 24012380
TI  - Synthesis and antiprotozoal activity of dicationic 2,6-diphenylpyrazines and aza
      analogues.
AB  - Dicationic 2,6-diphenylpyrazines, aza-analogues and prodrugs were synthesized;
      evaluated for DNA affinity, activity against Trypanosoma brucei rhodesiense (T.
      b. r.) and Plasmodium falciparum (P. f.) in vitro, efficacy in T. b. r. STIB900
      acute and T. b. brucei GVR35 CNS mouse models. Most diamidines gave poly(dA-dT)2
      DeltaTm values greater than pentamidine, IC50 values: T. b. r. (4.8-37nM) and P.
      f. (10-52nM). Most diamidines and prodrugs gave cures for STIB900 model (11, 19a
      and 24b 4/4 cures); 12 3/4 cures for GVR35 model. Metabolic stability half-life
      values for O-methylamidoxime prodrugs did not correlate with STIB900 results. 

PMID- 24012382
TI  - Factorial validity of the English-language version of the Pain Catastrophizing
      Scale--child version.
AB  - The Pain Catastrophizing Scale (PCS) was developed in English to assess 3
      components of catastrophizing (rumination, magnification, helplessness). It has
      been adapted for use and validated with Flemish-speaking children (Pain
      Catastrophizing Scale for Children [PCS-C]) and French-speaking adolescents. The
      PCS-C has been back-translated to English and used extensively in research with
      English-speaking children; however, the factorial validity of the English PCS-C
      has not been empirically examined. This study assessed the factor structure of
      the English PCS-C among a community sample of 1,006 English-speaking children
      (aged 8-18 years). Exploratory factor analysis was conducted using a random
      subsample (n = 504) to assess the underlying factor structure. Items with poor
      factor loadings were removed. Confirmatory factor analysis, using the second
      subsample (n = 502), was used to cross-validate the factor structure revealed by
      exploratory factor analysis and compare it to the original 3-factor model and
      other model variants. Exploratory factor analysis revealed that the original PCS
      C and a revised 3-factor model comprising 11 of the original 13 PCS-C items, all
      loading on their original factors, provided adequate fit to the data. The revised
      model provided statistically better fit to the data compared to all other model
      variants, suggesting that the English PCS-C may be better understood using a
      revised 11-item oblique 3-factor model. PERSPECTIVE: This is the first
      examination of the factorial validity of the widely used English version of the
      PCS-C in a large community sample of English-speaking children. A revised 11
      item, 3-factor model provided statistically better fit to the data compared to
      the original model and other model variants.

PMID- 24012383
TI  - Enzymatic characterizations and activity regulations of N-acetyl-beta-D
      glucosaminidase from the spermary of Nile tilapia (Oreochromis niloticus).
AB  - N-Acetyl-beta-D-glucosaminidase (NAGase) is proved to be correlated with
      reproduction of male animals. In this study, enzymatic characterizations of
      NAGase from spermary of Nile tilapia (Oreochromis niloticus) were investigated in
      order to further study its reproductive function in fish. Tilapia NAGase was
      purified to be PAGE homogeneous by the following techniques: (NH4)2SO4
      fractionation (40-55%), DEAE-cellulose (DE-32) ion exchange chromatography,
      Sephadex G-200 gel filtration and DEAE-Sephadex (A-50). The specific activity of
      the purified enzyme was 4100 U/mg. The enzyme molecular weight was estimated as
      118.0 kD. Kinetic studies showed that the hydrolysis of p-nitrophenyl-N-acetyl
      beta-D-glucosaminide (pNP-NAG) by the enzyme followed Michaelis-Menten kinetics.
      The Michaelis-Menten constant (Km) and maximum velocity (Vm) were determined to
      be 0.67 mM and 23.26 MUM/min, respectively. The optimum pH and optimum
      temperature of the enzyme for hydrolysis of pNP-NAG was to be at pH 5.7 and 55
      degrees C, respectively. The enzyme was stable in a pH range from 3.3 to 8.1 at
      37 degrees C, and inactive at temperature above 45 degrees C. The enzyme activity
      was regulated by the following ions in decreasing order: Hg(2+) > Zn(2+) > Cu(2+)
      > Pb(2+) > Mn(2+). The IC50 of Cu(2+), Zn(2+) and Hg(2+) was 1.23, 0.28, and
      0.0027 mM, respectively. However, the ions Li(+), Na(+), K(+), Mg(2+) and Ca(2+)
      had almost no influence on enzyme activity. In conclusion, the enzymatic
      characterizations of NAGase from tilapia were special to the other animals, which
      were correlated with its living habit; besides, CuSO4 and ZnSO4 should used very
      carefully as insecticides in tilapia cultivation since they both had strong
      regulations on the enzyme.

PMID- 24012384
TI  - Characteristics of traditional Chinese shanlan wine fermentation.
AB  - Shanlan rice wine is made by a unique method by removing the saccharified liquid
      from wine mash constantly since it appeared during saccharification and
      fermentation. The objective of this study is to find the advantages of this
      technique of wine making by analyzing data of shanlan wine fermentation. Since
      the liquid was removed, the mash (rice) bed was fluffier than immersed in the
      saccharified liquid, under ambient condition constantly and it is favorable for
      starch degradation. This technique made shanlan rice wine tasted sweet and
      slightly acidic, lower content of alcohol and higher alcohol than in other non
      distilled rice wines. 

PMID- 24012385
TI  - Primary large B-cell lymphoma of the fourth ventricle.
AB  - We present a patient with an isolated primary central nervous system lymphoma
      (PCNSL) of the fourth ventricle. A 77-year-old man had a 1 week history of
      intermittent vertigo, nausea, vomiting, and progressively unsteady gait. CT scans
      of the brain showed a fourth ventricle tumor. MRI revealed a 2.5 cm dumbbell
      shaped avidly-enhancing tumor in the fourth ventricle. Metastasis or high-grade
      glioma was suspected. The neuropathological findings were compatible with a
      diffuse large B-cell lymphoma. A slit lamp examination, bone marrow biopsy, and
      imaging studies for extracranial lesions were unremarkable. We suggest that PCNSL
      be listed in the differential diagnosis of fourth ventricle tumors with well
      circumscribed margins and homogenous contrast enhancement.

PMID- 24012386
TI  - Pharmacovigilance knowledge in family paediatricians. A survey study in Italy.
AB  - Drugs prescription in children correlates with a high risk of developing unknown
      or rare adverse drug reactions (ADRs). In the absence of appropriate clinical
      trials in the paediatric population, the spontaneous reporting of suspected ADRs
      is an important means to promote reasonable warning signals. In this context,
      family paediatricians (FPs) play a crucial role although a general poor
      compliance in their ability of reporting of ADR is widely described. To
      understand the reasons beyond this situation we performed a survey, the first of
      its kind in Italy, to evaluate FPs knowledge, feeling and compliance in ADR
      reporting. A total of 552 FPs evenly distributed throughout the Italian territory
      provided a feedback to the survey. Knowledge of pharmacovigilance (PV) resulted
      to be poor, mainly due to the absence of adequate training in academy; despite
      this, the majority of FPs declared to be interested to PV and aware of its
      positive impact on their clinical practice. Yet, FPs reported a poor compliance
      to the reporting of ADRs. A very high variability in ADRs reporting however, was
      observed among the regions, possibly because of variability of regional
      educational programmes dedicated to PV. 

PMID- 24012387
TI  - Educational programmes in COPD management interventions: a systematic review.
AB  - BACKGROUND: According to practice guidelines, educational programmes for patients
      with COPD should address several educational topics. Which topics are
      incorporated in the existing programmes remains unclear. OBJECTIVES: To delineate
      educational topics integrated in current COPD management interventions; and to
      examine strengths, weaknesses, and methods of delivery of the educational
      programmes. DATA SOURCES: A systematic literature search was performed using
      MEDLINE/PubMed, Cochrane Central Registry of Controlled Clinical Trials, and Web
      of Science. The authors of included studies were contacted for additional
      information. STUDY SELECTION: Studies that contained educational programmes
      incorporated in COPD management interventions were included. DATA EXTRACTION:
      Data were extracted using a pre-designed data form. The Reach, Efficacy,
      Adoption, Implementation and Maintenance (RE-AIM) framework was used for
      evaluating the strengths and weaknesses of the programmes. DATA SYNTHESIS: In
      total, 81 articles, describing 67 interventions were included. The majority
      (53.8%) of the studies incorporated 10 or more educational topics. The following
      topics were frequently addressed: smoking cessation (80.0%); medication (76.9%);
      exercise (72.3%); breathing strategies (70.8%); exacerbations (69.2%); and stress
      management (67.7%). Printed material and/or brochure (90.5%) and demonstrations
      and practice (73.8%), were the predominant tool and method, respectively. Nurses
      (75.8%), physicians (37.9%) and physiotherapists (34.8%) were the most involved
      healthcare professionals. CONCLUSIONS: Heterogeneity and wide variation in the
      content and the method of delivery of educational interventions were present.
      Alignment between educational topics incorporated in the existing programmes and
      those recommended by the COPD guidelines, involvement of various professionals
      and combined use of methods should be emphasised.

PMID- 24012388
TI  - Pressure-controlled ventilation and sleep in COPD patients in the intensive care
      unit: The role of tidal volume?

PMID- 24012389
TI  - A modified NARMAX model-based self-tuner with fault tolerance for unknown
      nonlinear stochastic hybrid systems with an input-output direct feed-through
      term.
AB  - A modified nonlinear autoregressive moving average with exogenous inputs (NARMAX)
      model-based state-space self-tuner with fault tolerance is proposed in this paper
      for the unknown nonlinear stochastic hybrid system with a direct transmission
      matrix from input to output. Through the off-line observer/Kalman filter
      identification method, one has a good initial guess of modified NARMAX model to
      reduce the on-line system identification process time. Then, based on the
      modified NARMAX-based system identification, a corresponding adaptive digital
      control scheme is presented for the unknown continuous-time nonlinear system,
      with an input-output direct transmission term, which also has measurement and
      system noises and inaccessible system states. Besides, an effective state space
      self-turner with fault tolerance scheme is presented for the unknown
      multivariable stochastic system. A quantitative criterion is suggested by
      comparing the innovation process error estimated by the Kalman filter estimation
      algorithm, so that a weighting matrix resetting technique by adjusting and
      resetting the covariance matrices of parameter estimate obtained by the Kalman
      filter estimation algorithm is utilized to achieve the parameter estimation for
      faulty system recovery. Consequently, the proposed method can effectively cope
      with partially abrupt and/or gradual system faults and input failures by the
      fault detection. 

PMID- 24012390
TI  - Changes in plasma adipokines in prepubertal children with a history of
      extrauterine growth restriction.
AB  - OBJECTIVE: Because nutritional support in perinatal life has been associated with
      metabolic programming, children with a history of extrauterine growth restriction
      (EUGR) might display alterations in the adipocyte and in the secretion of
      adipokines. The aim of this study was to assess adiponectin, resistin, and leptin
      concentrations in prepubertal children with a history of EUGR, and to determine
      the potential correlation between these adipokines and metabolic parameters.
      METHODS: This case-control study sample included 38 prepubertal children with a
      history of EUGR and a control group of 123 healthy children of similar age and
      sex. Anthropometric measures and blood pressure were assessed. Biochemical
      markers and blood adipokine concentrations (adiponectin, resistin, and leptin)
      were evaluated. RESULTS: Adiponectin concentration was significantly lower in the
      EUGR group compared with controls (EUGR: 11.49 +/- 6.07 versus control: 25.72 +/-
      10.13 MUg/mL), and resistin concentration was higher (EUGR: 20332.95 +/- 6401.25
      versus control: 8056.31 +/- 3823.63 pg/mL), even after adjustment for gestational
      age, weight, and size at birth. Systolic blood pressure was associated with
      adipokines concentrations in the EUGR group (P < 0.001). In EUGR children
      adiponectin was associated with high-density lipoprotein cholesterol (P = 0.042),
      whereas resistin was associated with carbohydrate metabolism parameters (P <
      0.001). CONCLUSIONS: Early postnatal malnutrition in EUGR children could program
      adipose tissue. Plasma adipokines can be measured in childhood to identify
      precocious changes that may be associated with a higher risk for metabolic
      syndrome or cardiovascular disease later in life.

PMID- 24012391
TI  - Effects of resveratrol on obesity-related inflammation markers in adipose tissue
      of genetically obese rats.
AB  - OBJECTIVE: The aim of this study was to examine whether resveratrol might
      represent a promising therapeutic tool with which to combat adipose tissue
      chronic inflammation in a model of genetic obesity and to link its anti
      inflammatory activity with its effect on body fat reduction. METHODS: Twenty 6-wk
      old male Zucker (fa/fa) rats were randomly distributed into two experimental
      groups. Resveratrol (RSV) was given orally (15 mg/kg body weight/d in RSV group)
      by means of an orogastric catheter for 6 wk. Enzyme activities were measured
      spectrophotometrically or fluorimetrically. Gene and protein expressions were
      analyzed by reverse transcriptase polymerase chain reaction and Western blot
      respectively. Cytokine concentrations and the activity of nuclear factor kappa
      light-chain-enhancer of activated beta cells (NF-kappaB) were measured by using
      commercial kits. RESULTS: RSV reduced the weight of internal adipose tissues. In
      epididymal depot glucose-6P-dehydrogenase, acetyl-CoA carboxylase activities, as
      well as lipoprotein lipase expression and activity were reduced by RSV. The
      expression of hormone-sensitive lipase was increased, and that of the cluster of
      differentiation 36 was reduced. Serum concentrations of tumor necrosis factor
      alpha, monocyte chemoattractant protein 1, and C-reactive protein were lower in
      the RSV-treated group than in the control group. Protein expression of
      interleukin-6 and the activity of NF-kappaB, were decreased by RSV. CONCLUSION:
      The present results provide evidence that fatty acid uptake and lipolysis are
      metabolic pathways involved in the response of adipose tissue to RSV. This
      polyphenol modulates plasma cytokine levels partially by reducing macrophage
      infiltration in adipose tissue and inhibiting NF-kappaB activity.

PMID- 24012392
TI  - Targeting angiogenesis and the tumor microenvironment.
AB  - The role of the microenvironment during the initiation and progression of
      malignancy is appreciated to be of critical importance for improved molecular
      diagnostics and therapeutics. The tumor microenvironment is the product of a
      crosstalk between different cells types. Active contribution of tumor-associated
      stromal cells to cancer progression has been recognized. Stromal elements consist
      of the extracellular matrix, fibroblasts of various phenotypes, and a scaffold
      comprised of immune and inflammatory cells, blood and lymph vessels, and nerves.
      This review focuses on therapeutic targets in the microenvironment related to
      tumor endothelium, tumor associated fibroblasts, and the extracellular matrix. 

PMID- 24012394
TI  - Targeting the heat shock response in cancer: tipping the balance in transformed
      cells.
AB  - The elucidation of the heat shock response (HSR) as a mediator of cellular stress
      has created a framework for understanding how these processes may promote
      tumorigenesis. Furthermore, the identification of specific components of the HSR
      and how they are co-opted by cancer cells has led to the discovery of new
      therapeutic targets. A wide range of small molecule inhibitors of the HSR are in
      various stages of development for clinical application in patients with cancer.
      The introduction of these novel small molecule inhibitors offers the opportunity
      for synergy with existing therapies and the potential for highly targeted
      treatments. 

PMID- 24012395
TI  - Targeting receptor tyrosine kinases in solid tumors.
AB  - Tyrosine kinase (TK) cascades are involved in all stages of tumorigenesis through
      modulation of transformation and differentiation, cell-cycle progression, and
      motility. Advances in molecular targeted drug development allow the design and
      synthesis of inhibitors targeting cancer-associated signal transduction pathways.
      Potent selective inhibitors with low toxicity can benefit patients with local and
      metastatic malignancies. This article evaluates information on solid tumor
      related TK signaling and inhibitors, including receptor TK signal pathways that
      lead to successful application in clinical settings, properties of recently
      approved TK-inhibitor drugs for the treatment of solid tumors, and potential TK
      pathways for future therapeutic interventions. 

PMID- 24012396
TI  - Targeting the NF-kappaB pathway in cancer therapy.
AB  - Most NF-kappaB inhibitors target the IKK complex, IkappaB proteins, or NF-kappaB
      transcription factors. The most promising classes of inhibitors include
      antioxidants, antiinflammatory compounds, natural compounds, statins, proteasome
      inhibitors, IKKbeta inhibitors, biologics, gene therapy, and RNA interference.
      Targeting NF-kappaB is limited by intrinsic pathway complexity, cross-talk with
      other pathways, a lack of biomarkers, poor drug specificity, drug resistance, and
      difficulty with drug delivery. Future NF-kappaB targeting will be improved
      through better understanding of the pathway, more specific inhibitors, and
      multimodality therapies.

PMID- 24012393
TI  - Targeting the PI3-kinase/Akt/mTOR signaling pathway.
AB  - This article presents an overview of the PI3K/Akt/mTOR signaling pathway. As a
      central regulator of cell growth, protein translation, survival, and metabolism,
      activation of this signaling pathway contributes to the pathogenesis of many
      tumor types. Biochemical and genetic aberrations of this pathway observed in
      various cancer types are explored. Last, pathway inhibitors both in development
      and already approved by the Food and Drug Administration are discussed. 

PMID- 24012398
TI  - Cancer immunotherapy: current status and future directions.
AB  - Better understanding of the underlying principles of tumor biology and
      immunology, enhanced by recent insights into the mechanisms of immune
      recognition, regulation, and tumor escape has provided new approaches for cancer
      immunotherapy. This article reviews the current status and future directions of
      cancer immunotherapy, with a focus on the recent encouraging results from immune
      modulating antibodies and adoptive cell therapy. 

PMID- 24012399
TI  - Translational research in melanoma.
AB  - Recent breakthroughs in the fundamental understanding of the cellular and
      molecular basis of melanoma have culminated in new therapies with unquestionable
      efficacy. Immunotherapy and targeted therapy strategies have completely
      transformed the contemporary management of advanced melanoma. The translational
      research behind these developments is discussed, with an emphasis on immune
      checkpoint blockade and inhibition of the mitogen-activated protein kinase
      signaling pathway. 

PMID- 24012397
TI  - Targeting the p53 pathway.
AB  - This article summarizes data on translational studies to target the p53 pathway
      in cancer. It describes the functions of the p53 and Mdm-2 signaling pathways,
      and discusses current therapeutic approaches to target p53 pathways, including
      reactivation of p53. In addition, direct interaction and colocalization of the
      p53 and focal adhesion kinase proteins in cancer cells have been demonstrated,
      and different approaches to target this interaction are reviewed. This is a broad
      review of p53 function as it relates to the diagnosis and treatment of a wide
      range of cancers. 

PMID- 24012401
TI  - Advances in molecular and clinical subtyping of breast cancer and their
      implications for therapy.
AB  - The identification of the intrinsic molecular subtypes of breast cancer has
      enhanced our understanding of tumor biology, informing therapeutic targets, and
      clinical trial design. This article reviews the intrinsic classification system
      and the clinically defined subtypes of breast cancer. We review the molecular
      drivers of each subtype and discuss implications for prognosis, clinical
      management, and future directions. 

PMID- 24012402
TI  - Biomarkers and targeted therapeutics in colorectal cancer.
AB  - The development of colorectal cancer is characterized by a multitude of molecular
      events that can occur through the pathways of loss of heterozygosity,
      microsatellite instability, and CpG-island methylation. The accumulation of these
      molecular events ultimately results in polyps formed from previously normal
      mucosa to develop the fundamental characteristics of cancerization: uncontrolled
      proliferation, growth, and invasion. Advances in the understanding of molecular
      events leading to colorectal cancer have led to the development of biomarkers,
      patient-specific and tumor-specific molecular signatures that have potential as
      tools for accurate risk assessment, personalized treatment planning, development
      of targeted agents, and evaluation of treatment response. 

PMID- 24012404
TI  - Getting from the bench to the patient: biotechnology strategies.
AB  - Despite significant advances in understanding of molecular pathobiology, the
      adoption of this knowledge and its application to drug development is sporadic.
      Consequently, the drug development process has remained intrinsically laborious
      and inefficient. Translational research seeks to improve this process by
      integrating scientific advances into well-defined clinical challenges and
      opportunities. The focus of this article is on cancer therapeutics, specifically,
      2 biotechnology organizations' advances in oncology: (1) optimizing the safety
      and efficacy of a novel DNA cross-linking small molecule, palifosfamide, and (2)
      bringing synthetic biology into clinical practice using a controllable gene
      therapy strategy with intratumorally injected interleukin-12 DNA, a potent
      cytokine.

PMID- 24012405
TI  - Translational cancer research for surgeons. Foreword.

PMID- 24012400
TI  - Targeted therapy for cancer: the gastrointestinal stromal tumor model.
AB  - Gastrointestinal stromal tumors (GISTs) are unique tumors, arising largely due to
      oncogenic mutations in KIT or PDGFRA tyrosine kinases. Although surgery remains
      the most effective treatment, the remarkable clinical success achieved with
      kinase inhibition has made GIST one of the most successful examples of targeted
      therapy for the treatment of cancer. The insight gained from this approach has
      allowed a deeper understanding of the molecular biology driving kinase dependent
      cancers, and the adaptations to kinase inhibition, linking genotype to phenotype.
      Mutation tailored kinase inhibition with second generation TKI's, and combination
      immunotherapy to harness the effects of TKIs remain exciting areas of
      investigation.

PMID- 24012406
TI  - Translational cancer research for surgeons.

PMID- 24012403
TI  - Translational research in endocrine surgery.
AB  - This article reviews translational research in endocrine surgery, with a focus on
      disorders of the thyroid, parathyroids, adrenals, and endocrine pancreas.
      Discovery of genes responsible for heritable endocrine cancer syndromes has
      increased knowledge of the causes and mechanisms of endocrine cancer and has
      refined surgical treatment options. Knowledge of mutations in sporadic cancer has
      led to rapid progress in small-molecule kinase inhibitor strategies. These
      breakthroughs and their influence on current therapy are discussed to provide
      surgeons with an overview of the basic science research currently creating new
      clinical treatments and improving patient care. 

PMID- 24012407
TI  - Competencies in Swedish emergency departments - The practitioners' and managers'
      perspective.
AB  - The task of emergency departments (EDs) is to provide safe emergency healthcare
      while adopting a caring, cost-effective approach. Patients attending EDs have
      different medical and caring needs and it is assumed that practitioners have the
      requisite competencies to meet those needs. The aim of the present study is to
      explore what kind of competencies practitioners and managers describe as
      necessary for the practitioners to perform their everyday work in EDs. METHODS:
      This study used a qualitative, exploratory design. Interviews were conducted in
      two EDs. Data were analysed using inductive content analysis. RESULTS: The
      competence focus in everyday work in EDs is on emergency and life-saving actions.
      There is a polarisation between medical and caring competencies. There is also
      tension between professional groups in EDs as well as hierarchical boundaries
      that influence the ability to develop competencies in everyday work. Medical
      competencies are valued more and caring competencies are subsequently downgraded.
      A medical approach to competencies consolidates the view of necessary
      competencies in everyday work in EDs. CONCLUSIONS: The study shows that the
      competencies that are valued consolidate the prevailing medical paradigm. There
      is a traditional, one-sided approach to competencies, a hierarchical distinction
      between professional groups and unclear occupational functions.

PMID- 24012409
TI  - Intracerebral haemorrhage and cognitive decline.
AB  - Relationships between intracerebral hemorrhage (ICH) and dementia might be of
      interest since some causes of ICH such as cerebral amyloid angiopathy are
      strongly linked with dementia, especially Alzheimer's disease. The aim of this
      narrative review was to highlight the interesting relationship of ICH lesions and
      cognitive decline leading to dementia. We considered the whole spectrum of
      hemorrhagic lesions in the brain parenchyma, namely spontaneous ICH and brain
      microbleeds. 

PMID- 24012408
TI  - Presymptomatic studies in genetic frontotemporal dementia.
AB  - Approximately 20% of patients with the neurodegenerative disorder frontotemporal
      dementia (FTD) have an autosomal dominant pattern of inheritance. Genetic FTD is
      caused by mutations in three genes in most cases (progranulin, microtubule
      associated protein tau and chromosome 9 open reading frame 72) although a number
      of other genes are rare causes. Studies of other neurodegenerative diseases have
      shown imaging and biomarker evidence of disease onset many years prior to the
      development of symptoms. Similar studies in genetic FTD are now revealing
      evidence of a series of presymptomatic changes, initially in plasma biomarkers
      followed by MR imaging abnormalities of functional and structural connectivity
      and then grey matter atrophy. Lastly, neuropsychometric tests become abnormal in
      proximity to the onset of symptoms. Such studies have been relatively small until
      now but research centres with an expertise in genetic FTD are now forming
      consortia such as the Genetic Frontotemporal Dementia Initiative (GenFI) to
      create larger cohorts that can form the basis of future clinical trials. 

PMID- 24012410
TI  - Clinical training stress-inducing factors from the students' viewpoint: a
      questionnaire-based study.
AB  - Improving the quality of clinical training requires provision of suitable
      educational environment and one of its requirements is determination of the
      stress-inducing factors. The present research was carried out to explore these
      factors from the viewpoint of students of nursing school. This research was a
      descriptive study. The samples included a total of 230 students who had passed at
      least one credit of clinical training and had been selected through convenience
      sampling. Based on the research results, the most tension-inducing area was
      related to the unpleasant emotions area, clinical experiences, unpleasant
      feelings, educational environment and interpersonal relationships, respectively.
      Throughout clinical training processes, students of different medical fields face
      a great deal of tension-inducing factors. The identification of these factors
      could play a significant role in reducing the amount of tension among them. 

PMID- 24012411
TI  - Transformation to small-cell lung cancer following treatment with EGFR tyrosine
      kinase inhibitors in a patient with lung adenocarcinoma.
AB  - We report the case of a 52-year-old woman with lung adenocarcinoma treated with
      EGFR tyrosine kinase inhibitor (TKI) therapy. After disease progression,
      histological examination of a secondary biopsy specimen revealed small-cell lung
      cancer (SCLC) that was sensitive to standard SCLC treatment. Tumor markers,
      including ProGRP and NSE, were elevated. Transformation to SCLC is a mechanism
      for acquired resistance to EGFR-TKI therapy. Secondary biopsy is important for
      evaluation of genetic and histological changes and selection of appropriate
      treatment. Furthermore, ProGRP and NSE may be useful for early detection of SCLC
      transformation in cases resistant to EGFR-TKI therapy. 

PMID- 24012412
TI  - High risk of gastrointestinal hemorrhage in patients with epilepsy: a nationwide
      cohort study.
AB  - OBJECTIVE: To examine the association between epilepsy and gastrointestinal
      hemorrhage. PATIENTS AND METHODS: We conducted a nationwide retrospective cohort
      study by using data from Taiwan's National Health Insurance Research Database.
      Patients 20 years and older newly diagnosed as having epilepsy and nonepileptic
      adults were identified between January 1, 2000, and December 31, 2003, and were
      observed through December 31, 2008. Cox proportional hazards models were
      performed to calculate adjusted hazard ratios (HRs) and 95% CIs of
      gastrointestinal hemorrhage associated with epilepsy. RESULTS: Compared with the
      nonepileptic group (n=449,541), epileptic patients (n=1412) had a higher
      incidence of gastrointestinal hemorrhage (13.4 vs 2.9 per 1000 person-years),
      with an HR of 2.97 (95% CI, 2.49-3.53). The HRs of gastrointestinal hemorrhage
      for patients with generalized epilepsy, inpatient care, emergency care, and
      frequent outpatient visits for epilepsy were 3.50 (95% CI, 2.59-4.72), 3.96 (95%
      CI, 2.85-5.50), 4.35 (95% CI, 3.15-6.01), and 4.96 (95% CI, 3.97-6.21),
      respectively. Risks were significantly higher in epileptic patients with mental
      disorders (HR, 3.20; 95% CI, 2.55-4.01), aged 70 years and older (HR, 4.08; 95%
      CI, 2.89-5.77), and in the first year after epilepsy (HR, 4.81; 95%, CI, 3.14
      7.34). CONCLUSION: Epilepsy is an independent determinant for gastrointestinal
      hemorrhage in a chronological and severity-dependent pattern. We urge the
      development of an adequate surveillance policy and strategy for the early
      prevention of gastrointestinal hemorrhage in epileptic patients.

PMID- 24012413
TI  - Proton Pump Inhibitors and the Risk for Hospital-Acquired Clostridium difficile
      Infection.
AB  - OBJECTIVE: To examine the relationship between proton pump inhibitor (PPI) usage
      and nosocomial Clostridium difficile infection (CDI) and determine the duration
      of therapy at which CDI risk increases. PATIENTS AND METHODS: This retrospective
      case-control study included consecutive adult patients in whom nosocomial CDI
      developed after hospitalization for 3 or more days at one of 2 affiliated
      hospitals between June 1, 2010, and October 31, 2011. These patients were matched
      to patients hospitalized within 6 months who did not have CDI development in a
      1:2 ratio using age, sex, and antibiotic usage. Potential risk factors for CDI,
      including PPI use and duration, were evaluated. Multivariate analysis was
      performed to control for confounding variables and identify risk factors.
      RESULTS: A total of 201 patients were evaluated, 67 with CDI and 134 matched
      controls. Patients in whom CDI developed were more likely to have received a PPI
      (76% vs 39%; P<.001) and had a longer duration of PPI therapy (median [range], 5
      [0-20] days vs 0 [0-11] days; P<.001) than those who did not have CDI
      development. After controlling for prior hospital admission, intensive care unit
      admission, admission from a skilled nursing facility, immunosuppression, number
      of antibiotics received, PPI duration, and time to event via multivariate
      analysis, PPI duration was found to be a risk factor for CDI (odds ratio, 1.14;
      95% CI, 1.02-1.27; P=.018). The probability for CDI was higher when PPI use
      exceeded 2 days in patients without a prior hospital admission and 1 day in
      patients with a prior admission. CONCLUSION: The duration of PPI therapy is
      significantly associated with CDI. Clinicians should strongly consider
      restricting PPI use given the short exposure time associated with this increased
      risk.

PMID- 24012414
TI  - Surgical site infections and mortality in elderly patients.
AB  - OBJECTIVE: We present the characteristics and outcome of surgical site infections
      (SSI) in patients 65 years of age or more, and determine the factors influencing
      mortality. METHODS: We conducted a prospective observational cohort study,
      comparing patients who survived with those who died, to identify risk factors
      associated with mortality among elderly patients presenting with SSI. The
      diagnosis of SSI was made for each patient, according to the CDC's standardized
      criteria. RESULTS: Seventy-five patients presenting with SSI were included in the
      study. The mean age of patients was 75 +/- 6 (65-92), 68% were male patients. The
      most frequently isolated pathogen was Acinetobacter baumannii (n = 24). The
      overall in-hospital mortality rate was 25.3%. The statistical analysis revealed
      that gastrointestinal surgery, organ/space infections, polymicrobial infections,
      and higher SOFA scores were significantly associated with hospital mortality (P =
      0.005, P = 0.0001, P = 0.047, P = 0.0001). According to laboratory tests, higher
      white blood cell (WBC) and neutrophil count, higher total bilirubin level, and
      lower thrombocyte count and albumin levels were significantly associated with
      hospital mortality (P = 0.040, P = 0.014, P = 0.001, P = 0.019, P=0.002).
      Multivariate analyses revealed that serum albumin (P = 0.004, OR = 11.3, CI 95%
      2.16-59.07), organ/space SSI (P = 0.0001, OR = 11.65, CI 95% 3.003-45.21), and
      SOFA score (P = 0.030, OR = 2.742, 1.100-6.84) were independent risk factors
      associated with mortality. CONCLUSIONS: Serum albumin levels, organ/space
      infections, and higher SOFA scores were independently significantly associated
      with hospital mortality in older patients with SSI. Serum albumin levels should
      be closely monitored, and if necessary, early surgery should be performed.

PMID- 24012415
TI  - [Post-partum infectious sacroiliitis].

PMID- 24012416
TI  - Minimal differentiation of classical monocytes as they survey steady-state
      tissues and transport antigen to lymph nodes.
AB  - It is thought that monocytes rapidly differentiate to macrophages or dendritic
      cells (DCs) upon leaving blood. Here we have shown that Ly-6C+ monocytes
      constitutively trafficked into skin, lung, and lymph nodes (LNs). Entry was
      unaffected in gnotobiotic mice. Monocytes in resting lung and LN had similar gene
      expression profiles to blood monocytes but elevated transcripts of a limited
      number of genes including cyclo-oxygenase-2 (COX-2) and major histocompatibility
      complex class II (MHCII), induced by monocyte interaction with endothelium.
      Parabiosis, bromodoxyuridine (BrdU) pulse-chase analysis, and intranasal
      instillation of tracers indicated that instead of contributing to resident
      macrophages in the lung, recruited endogenous monocytes acquired antigen for
      carriage to draining LNs, a function redundant with DCs though differentiation to
      DCs did not occur. Thus, monocytes can enter steady-state nonlymphoid organs and
      recirculate to LNs without differentiation to macrophages or DCs, revising a long
      held view that monocytes become tissue-resident macrophages by default.

PMID- 24012417
TI  - Synergistic activation of inflammatory cytokine genes by interferon-gamma-induced
      chromatin remodeling and toll-like receptor signaling.
AB  - Synergistic activation of inflammatory cytokine genes by interferon-gamma (IFN
      gamma) and Toll-like receptor (TLR) signaling is important for innate immunity
      and inflammatory disease pathogenesis. Enhancement of TLR signaling, a previously
      proposed mechanism, is insufficient to explain strong synergistic activation of
      cytokine production in human macrophages. Rather, we found that IFN-gamma induced
      sustained occupancy of transcription factors STAT1, IRF-1, and associated histone
      acetylation at promoters and enhancers at the TNF, IL6, and IL12B loci. This
      priming of chromatin did not activate transcription but greatly increased and
      prolonged recruitment of TLR4-induced transcription factors and RNA polymerase II
      to gene promoters and enhancers. Priming sensitized cytokine transcription to
      suppression by Jak inhibitors. Genome-wide analysis revealed pervasive priming of
      regulatory elements by IFN-gamma and linked coordinate priming of promoters and
      enhancers with synergistic induction of transcription. Our results provide a
      synergy mechanism whereby IFN-gamma creates a primed chromatin environment to
      augment TLR-induced gene transcription. 

PMID- 24012418
TI  - Histone methyltransferase Ash1l suppresses interleukin-6 production and
      inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme A20.
AB  - Histone modifications play important roles in multiple physiological processes by
      regulating gene expression. However, the roles of histone modifications in
      immunity remain poorly understood. Here we report that Ash1l, a H3K4
      methyltransferase, suppressed interleukin-6 (IL-6), and tumor necrosis factor
      (TNF) production in Toll-like receptor (TLR)-triggered macrophages, protecting
      mice from sepsis. Ash1l-silenced mice were more susceptible to autoimmune disease
      as a result of enhanced IL-6 production. Ash1l enhanced A20 expression through
      induction of H3K4 modification at the Tnfaip3 promoter via H3K4 methyltransferase
      activity of Ash1l SET (Su[var]3-9, E[z] and trithorax) domain. Ash1l suppressed
      NF-kappaB, mitogen-activated protein kinase (MAPK) pathways, and subsequent IL-6
      production via facilitating A20-mediated NF-kappaB signal modulator NEMO and
      transducer TRAF6 deubiquitination. Therefore, Ash1l-mediated H3K4 methylation at
      the Tnfaip3 promoter is required for controlling innate IL-6 production and
      suppressing inflammatory autoimmune diseases, providing mechanistic insight into
      epigenetic modulation of immune responses and inflammation. 

PMID- 24012419
TI  - SnapShot: innate lymphoid cells.

PMID- 24012421
TI  - The TACI receptor regulates T-cell-independent marginal zone B cell responses
      through innate activation-induced cell death.
AB  - Activation-induced cell death (AICD) plays a critical role in immune homeostasis
      and tolerance. In T-cell-dependent humoral responses, AICD of B cells is
      initiated by Fas ligand (FasL) on T cells, stimulating the Fas receptor on B
      cells. In contrast, T-cell-independent B cell responses involve innate-type B
      lymphocytes, such as marginal zone (MZ) B cells, and little is known about the
      mechanisms that control AICD during innate B cell responses to Toll-like receptor
      (TLR) activation. Here, we show that MZ B cells undergo AICD in response to TLR4
      activation in vivo. The transmembrane activator, calcium modulator, and
      cyclophilin ligand interactor (TACI) receptor and TLR4 cooperate to upregulate
      expression of both FasL and Fas on MZ B cells and also to repress inhibitors of
      Fas-induced apoptosis signaling. These findings demonstrate an unappreciated role
      for TACI and its ligands in the regulation of AICD during T-cell-independent B
      cell responses. 

PMID- 24012420
TI  - Myeloid-derived suppressor cells enhance stemness of cancer cells by inducing
      microRNA101 and suppressing the corepressor CtBP2.
AB  - Myeloid-derived suppressor cells (MDSCs) and cancer stem cells (CSCs) are
      important cellular components in the cancer microenvironment and may affect
      cancer phenotype and patient outcome. The nature of MDSCs and their interaction
      with CSCs in ovarian carcinoma are unclear. We examined the interaction between
      MDSCs and CSCs in patients with ovarian carcinoma and showed that MDSCs inhibited
      T cell activation and enhanced CSC gene expression, sphere formation, and cancer
      metastasis. MDSCs triggered miRNA101 expression in cancer cells. miRNA101
      subsequently repressesed the corepressor gene C-terminal binding protein-2
      (CtBP2), and CtBP2 directly targeted stem cell core genes resulting in increased
      cancer cell stemness and increasing metastatic and tumorigenic potential.
      Increased MDSC density and tumor microRNA101 expression predict poor survival, as
      does decreased tumor CtBP2 expression, independent of each other. Collectively,
      our work identifies an immune-associated cellular, molecular, and clinical
      network involving MDSCs-microRNA101-CtBP2-stem cell core genes, which
      extrinsically controls cancer stemness and impacts patient outcome. 

PMID- 24012422
TI  - The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism.
AB  - Mixed lineage kinase domain-like (MLKL) is a component of the "necrosome," the
      multiprotein complex that triggers tumor necrosis factor (TNF)-induced cell death
      by necroptosis. To define the specific role and molecular mechanism of MLKL
      action, we generated MLKL-deficient mice and solved the crystal structure of
      MLKL. Although MLKL-deficient mice were viable and displayed no hematopoietic
      anomalies or other obvious pathology, cells derived from these animals were
      resistant to TNF-induced necroptosis unless MLKL expression was restored.
      Structurally, MLKL comprises a four-helical bundle tethered to the pseudokinase
      domain, which contains an unusual pseudoactive site. Although the pseudokinase
      domain binds ATP, it is catalytically inactive and its essential nonenzymatic
      role in necroptotic signaling is induced by receptor-interacting serine-threonine
      kinase 3 (RIPK3)-mediated phosphorylation. Structure-guided mutation of the MLKL
      pseudoactive site resulted in constitutive, RIPK3-independent necroptosis,
      demonstrating that modification of MLKL is essential for propagation of the
      necroptosis pathway downstream of RIPK3. 

PMID- 24012423
TI  - The interrater reliability of ultrasound imaging of the inferior vena cava
      performed by emergency residents.
AB  - OBJECTIVE: Ultrasonography (US) has gained popularity in the emergency medicine
      to assess intravascular volume status in critically ill patients. However, there
      are a limited number of studies on the interrater reliability of US examination
      of the inferior vena cava (IVC) by emergency residents. METHOD: One hundred
      eighty US examinations were performed on 90 emergency critical care unit patients
      by 6 emergency medicine residents. Minimum and maximum IVC diameters during
      normal passive inspiration were measured, and the IVC index was calculated. The
      interrater reliability of the measurable data was analyzed using intraclass
      correlation coefficients. RESULTS: The measurements of minimum and maximum IVC
      diameters were moderately reliable by emergency residents (kappa = 0.60 [95%
      confidence interval {CI}, 0.45-0.72] and kappa = 0.56 [95% CI, 0.41-0.69],
      respectively). In the patients with moderate IVC depth (8.5-12.5 cm), the
      interrater reliabilities of sonographers were kappa = 0.51 (95% CI, 0.30-0.67)
      for maximum diameter and kappa = 0.43 (95% CI, 0.21-0.61) for minimum diameter.
      In patients with superficial (<=8.5 cm) and profound located (>=12.5 cm) IVC, the
      interrater reliabilities of sonographers for maximum and minimum diameters were
      kappa = 0.69 (95% CI, 0.29-0.89) and kappa = 0.75 (95% CI, 0.4-0.91), and kappa =
      0.58 (95% CI, 0.09-0.85) and kappa = 0.76 (95% CI, 0.39-0.92), respectively.
      CONCLUSION: The measurement of the IVC is moderately reliable by emergency
      residents. The interrater reliability of measurements in patients with profound
      and superficial located IVC is higher than that of measurements in patients with
      moderate-depth located IVC.

PMID- 24012424
TI  - A comparison of two techniques for tungsten carbide ring removal.
AB  - INTRODUCTION: Emergency physicians may have difficulty removing modern rings made
      of hard metals such as titanium and tungsten carbide. These metals are
      exceptionally difficult or impossible to remove using standard ring cutters.
      Numerous alternative techniques for removal have been described, including the
      "umbilical tape" or "string technique" and, in the case of tungsten carbide,
      breaking the ring using locking pliers. OBJECTIVE: We sought to compare the speed
      and effectiveness of tungsten carbide ring removal using these two techniques.
      METHODS: Ten tungsten carbide rings were placed upon the finger of a standard
      medical simulation mannequin. The rings chosen were one-half size smaller than
      the mannequin's finger. Edema distal to the ring was simulated using foam tape. A
      single novice operator performed 10 trials using each of the techniques after a
      10-minute orientation session. The success or failure of the technique and the
      time for removal were recorded for each trial. The mean removal times for the
      trials were compared using a paired t test. RESULTS: All trials were successful.
      The rings were removed substantially faster using the locking pliers method (mean
      23.1 seconds [95% CI 15.4-30.8] vs. mean 135.4 seconds [95% CI 130.2-150.6]).
      However, the locking pliers technique destroyed all rings and caused sharp ring
      fragments to be thrown up to 37 in. CONCLUSIONS: Both the umbilical tape or
      string technique and the locking pliers technique successfully removed tungsten
      carbide rings in our model. The locking pliers technique is significantly faster
      but destroys the ring and creates potentially harmful shrapnel.

PMID- 24012425
TI  - Alterations in physiology and anatomy during pregnancy.
AB  - Pregnant women undergo profound anatomical and physiological changes so that they
      can cope with the increased physical and metabolic demands of their pregnancies.
      The cardiovascular, respiratory, haematological, renal, gastrointestinal and
      endocrine systems all undergo important physiological alterations and adaptations
      needed to allow development of the fetus and to allow the mother and fetus to
      survive the demands of childbirth. Such alterations in anatomy and physiology may
      cause difficulties in interpreting signs, symptoms, and biochemical
      investigations, making the clinical assessment of a pregnant woman inevitably
      confusing but challenging. Understanding these changes is important for every
      practicing obstetrician, as the pathological deviations from the normal
      physiological alterations may not be clear-cut until an adverse outcome has
      resulted. Only with a sound knowledge of the physiology and anatomy changes can
      the care of an obstetric parturient be safely optimized for a better maternal and
      fetal outcome.

PMID- 24012426
TI  - Hsp70 chaperone dynamics and molecular mechanism.
AB  - The chaperone functions of heat shock protein (Hsp)70 involve an allosteric
      control mechanism between the nucleotide-binding domain (NBD) and polypeptide
      substrate-binding domain (SBD): ATP binding and hydrolysis regulates the affinity
      for polypeptides, and polypeptide binding accelerates ATP hydrolysis. These data
      suggest that Hsp70s exist in at least two conformational states. Although
      structural information on the conformation with high affinity for polypeptides
      has been available for several years, the conformation with an open polypeptide
      binding cleft was elucidated only recently. In addition, other biophysical
      studies have revealed a more dynamic picture of Hsp70s, shedding light on the
      molecular mechanism by which Hsp70s assist protein folding. In this review recent
      insights into the structure and mechanism of Hsp70s are discussed. 

PMID- 24012427
TI  - The effect of hypothermia on sensory-motor function and tissue sparing after
      spinal cord injury.
AB  - BACKGROUND CONTEXT: In recent years, hypothermia has been described as a
      therapeutic approach that leads to potential protective effects via minimization
      of secondary damage consequences, reduction of neurologic deficit, and increase
      of motor performance after spinal cord injury (SCI) in animal models and humans.
      PURPOSE: The objective of this study was to determine the therapeutic efficacy of
      hypothermia treatment on sensory-motor function and bladder activity outcome
      correlated with the white and gray matter sparing and neuronal survival after SCI
      in adult rats. STUDY DESIGN: A standardized animal model of compression SCI was
      used to test the hypothesis that hypothermia could have a neuroprotective effect
      on neural cell death and loss of white and/or gray matter. METHODS: Animals
      underwent spinal cord compression injury at the Th8-Th9 level followed by
      systemic hypothermia of 32.0 degrees C with gradual re-warming to 37.0 degrees C.
      Motor function of hind limbs (BBB score) and mechanical allodynia (von Frey hair
      filaments) together with function of urinary bladder was monitored in all
      experimental animals throughout the whole survival period. RESULTS: Present
      results showed that hypothermia had beneficial effects on urinary bladder
      activity and on locomotor function recovery at Days 7 and 14 post-injury.
      Furthermore, significant increase of NeuN-positive neuron survival within dorsal
      and ventral horns at Days 7, 14, and 21 were documented. CONCLUSIONS: Our
      conclusions suggest that hypothermia treatment may not only promote survival of
      neurons, which can have a significant impact on the improvement of motor and
      vegetative functions, but also induce mechanical allodynia.

PMID- 24012428
TI  - Nerve injury after lateral lumbar interbody fusion: a review of 919 treated
      levels with identification of risk factors.
AB  - BACKGROUND CONTEXT: Lateral lumbar interbody fusion (LLIF) has become an
      increasingly common minimally invasive procedure for selective degenerative
      deformity correction, reduction of low-grade spondylolisthesis, and indirect
      foraminal decompression. Concerns remain about the safety of the transpsoas
      approach to the spine due to proximity of the lumbosacral plexus. PURPOSE: To
      address risk factors for iatrogenic nerve injury in a large cohort of patients
      undergoing LLIF. STUDY DESIGN: Retrospective analysis of 919 LLIF procedures to
      identify risk factors for lumbosacral plexus injuries. METHODS: The medical
      charts of patients who underwent transpsoas interbody fusion with or without
      supplemental posterior fusion for degenerative spinal conditions over a 6-year
      period were retrospectively reviewed. Patients with prior lumbar spine surgery or
      follow-up of less than 6 months were excluded. Factors that may affect the
      neurologic outcome were investigated in a subset of patients who underwent stand
      alone LLIF. RESULTS: Four hundred fifty-one patients (males/females: 179/272) met
      the inclusion criteria and were followed for a mean of 15 months (range, 6-53
      months). Average age at the time of surgery was 63 years (range, 24-90 years).
      Average body mass index was 29 kg/m(2) (range, 17-65 kg/m(2)). A total of 919
      levels were treated (mean, 2 levels per patient). Immediately after surgery,
      38.5% of the patients reported anterior thigh/groin pain, whereas sensory and
      motor deficits were recorded in 38% and 23.9% of the patients, respectively. At
      the last follow-up, 4.8% of the patients reported anterior thigh/groin pain,
      whereas sensory and motor deficits were recorded in 24.1% and 17.3% of the
      patients, respectively. When patients with neural deficits present before surgery
      were excluded, persistent surgery-related sensory and motor deficits were
      identified in 9.3% and 3.2% of the patients, respectively. Among 87 patients with
      minimum follow-up of 18 months, persistent surgery-related sensory and motor
      deficits were recorded in 9.6% and 2.3% of the patients, respectively. Among
      patients with stand-alone LLIF, the level treated was identified as a risk factor
      for postoperative lumbosacral plexus injury. The use of recombinant human bone
      morphogenetic protein 2 was associated with persistent motor deficits.
      CONCLUSIONS: Although LLIF is associated with an increased prevalence of anterior
      thigh/groin pain as well as motor and sensory deficits immediately after surgery,
      our results support that pain and neurologic deficits decrease over time. The
      level treated appears to be a risk factor for lumbosacral plexus injury.

PMID- 24012429
TI  - Analysis of the techniques for thoracic- and lumbar-level localization during
      posterior spine surgery and the occurrence of wrong-level surgery: results from a
      national survey.
AB  - BACKGROUND CONTEXT: Despite the frequency with which surgeons perform posterior
      spinal surgery and the precautions against wrong-site surgery, operations on
      incorrect levels still occur. Wrong-level exposure is documented in 0.32% to 15%
      of cases. Additionally, there is little consensus as to what is the most accurate
      method for localizing the correct spinal level. PURPOSE: The purpose of this
      study is to investigate the most commonly used localization methods and their
      association with wrong-level surgery, to determine the prevalence of wrong-level
      localization, and to identify circumstances commonly associated with wrong-level
      surgery, and to offer recommendations that may reduce the incidence of these
      errors. STUDY DESIGN/SETTING: This was an online survey study that was
      distributed to North American Spine Society (NASS) members (including both
      orthopedic surgeons and neurosurgeons). The survey was sent as a Web link within
      an e-mail. PATIENT SAMPLE: A total of 2,338 surgeons received the survey, 532
      opened the survey, and 173 completed it (7.4% response rate). The survey was only
      sent once, as recommended by NASS. Of those that responded, 72% (124 of 173) were
      orthopedic surgeons, 28% (49 of 173) were neurosurgeons, and 73% (126 of 173)
      were spine fellowship trained. OUTCOME MEASURES: We sought to investigate self
      reported localization methods that are most commonly used (both anatomic
      landmarks and imaging techniques), the prevalence of wrong-level surgery, and any
      correlations between localization method and wrong-level surgery. METHODS: An
      eight-question anonymous survey was distributed to members of NASS, including
      orthopedic surgeons and neurosurgeons. There was no pilot testing or validation
      performed for this survey. The survey was sent as a Web link within an e-mail.
      Some questions asked surgeons to select as many responses as applicable, and
      others allowed surgeons to describe in detail any cases of wrong-level surgery.
      This study neither requires nor receives funding; additionally, no conflicts of
      interests were reported. RESULTS: Fluoroscopy was the most commonly used imaging
      technique for thoracic and lumbar surgeries (89% and 86%, respectively), followed
      by plain radiographs (54% and 58%, respectively). Surgeons were allowed to select
      as many responses as applicable, and 76 surgeons reported using both plain
      radiographs and fluoroscopy. The facet joint with corresponding pedicle was the
      most commonly used anatomic landmark for localization of thoracic and lumbar
      surgeries (67% and 59%, respectively), followed by the spinous process (49% and
      52%, respectively). Sixty-eight percent of surgeons admitted to wrong-level
      localization, some of which were rectified intraoperatively, during their
      careers. Fifty-six percent of these surgeons reported using plain radiographs and
      44% used fluoroscopy when the errors occurred. Common sources of preoperative
      errors included failure to visualize known reference points, recognize
      unconventional spinal anatomy, and adequately visualize the level because of
      large body habitus. Common sources of intraoperative errors included poor
      communication, failure to relocalize after exposure, and poor counting methods.
      CONCLUSIONS: Despite the variety of localization modalities, most surgeons use
      only a few. Whereas wrong-level localization is relatively rare, the ideal
      frequency is never. There is no standard approach that will entirely eliminate
      these mistakes; however, using a localization time out and increasing awareness
      of common sources of error may help decrease the incidence of wrong-level spine
      surgery.

PMID- 24012430
TI  - Twenty-year perspective of randomized controlled trials for surgery of chronic
      nonspecific low back pain: citation bias and tangential knowledge.
AB  - BACKGROUND CONTEXT: After decades of clinical research, the role of surgery for
      chronic nonspecific low back pain (CNLBP) remains equivocal. Despite significant
      intellectual, human, and economic investments into randomized controlled trials
      (RCTs) in the past two decades, the role of surgery in the treatment for CNLBP
      has not been clarified. PURPOSE: To delineate the historical research agenda of
      surgical RCTs for CNLBP performed between 1993 and 2012 investigating whether
      conclusions from earlier published trials influenced the choice of research
      questions of subsequent RCTs on elucidating the role of surgery in the management
      of CNLBP. STUDY DESIGN: Literature review. METHODS: We searched the literature
      for all RCTs involving surgery for CNLBP. We reviewed relevant studies to
      identify the study question, comparator arms, and sample size. Randomized
      controlled trials were classified as "indication" trials if they evaluated the
      effectiveness of surgical therapy versus nonoperative care or as "technical" if
      they compared different surgical techniques, adjuncts, or procedures. We used
      citation analysis to determine the impact of trials on subsequent research in the
      field. RESULTS: Altogether 33 technical RCTs (3,790 patients) and 6 indication
      RCTs (981 patients) have been performed. Since 2007, despite the unclear benefits
      of surgery reported by the first four indication trials published in 2001 to
      2006, technical trials have continued to predominate (16 vs. 2). Of the technical
      trials, types of instrumentation (13 trials, 1,332 patients), bone graft
      materials and substitutes (11 trials, 833 patients), and disc arthroplasty versus
      fusion (5 trials, 1,337 patients) were the most common comparisons made. Surgeon
      authors have predominantly cited one of the indication trials that reported more
      favorable results for surgery, despite a lack of superior methodology or sample
      size. Trials evaluating bone morphogenic protein, instrumentation, and disc
      arthroplasty were all cited more frequently than the largest trial of surgical
      versus nonsurgical therapy. CONCLUSIONS: The research agenda of RCTs for surgery
      of CNLBP has not changed substantially in the last 20 years. Technical trials
      evaluating nuances of surgical techniques significantly predominate. Despite the
      publication of four RCTs reporting equivocal benefits of surgery for CNLBP
      between 2001 and 2006, there was no change in the research agenda of subsequent
      RCTs, and technical trials continued to outnumber indication trials. Rather than
      clarifying what, if any, indications for surgery exist, investigators in the
      field continue to analyze variations in surgical technique, which will probably
      have relatively little impact on patient outcomes. As a result, clinicians
      unfortunately have little evidence to advise patients regarding surgical
      intervention for CNLBP.

PMID- 24012431
TI  - A case of miltefosine responsive pleomorphic post kala-azar dermal leishmaniasis.

PMID- 24012432
TI  - Comparison of peri-procedural platelet inhibition with prasugrel versus
      adjunctive cilostazol to dual anti-platelet therapy in patients with ST segment
      elevation myocardial infarction.
AB  - BACKGROUND: It has been well known that the inhibition of platelet aggregation
      (IPA) by anti-platelet agents was important to reduce the thrombo-embolic events
      in patients with ST segment elevation myocardial infarction (STEMI). However, the
      peri-procedural IPA by anti-platelet agents was not well known. METHODS: We
      compared the peri-procedural IPA between prasugrel and adjunctive cilostazol to
      dual anti-platelet therapy (triple anti-platelet therapy; TAP) in patients with
      STEMI undergoing primary percutaneous coronary intervention (PCI). We
      prospectively randomized 70 consecutive clopidogrel-naive patients with STEMI
      planned PCI to either prasugrel [loading dose (LD) 60 mg; 37 patients] or TAP (LD
      aspirin 300 mg, clopidogrel 600 mg, and cilostazol 200mg; 33 patients). Primary
      end points of the study were the platelet reactivity unit (PRU) or % inhibition
      by the VerifyNow P2Y12 assay at pre-PCI and pre-discharge. RESULTS: The drug
      loading to pre-PCI time was similar between prasugrel and TAP groups (25.4 +/-
      10.42 min vs. 25.5 +/- 10.56 min, p=0.957). PRU at pre-PCI was significantly
      lower in prasugrel than in TAP (269.1 +/- 71.69 vs. 306.5 +/- 48.67, p=0.012).
      The lower PRU and greater % inhibition also observed in prasugrel than in TAP at
      pre-discharge (108.2 +/- 60.51 vs. 238.1 +/- 73.40; 63.6 +/- 18.51% vs. 16.8 +/-
      17.91%, p<0.001 respectively). No differences in in-hospital bleeding
      complications between the two groups were observed. CONCLUSION: Our study
      demonstrates that prasugrel could produce a significantly greater peri-procedural
      as well as in-hospital IPA compared with TAP in patients with STEMI undergoing
      primary PCI.

PMID- 24012433
TI  - Elevated left ventricular filling pressure estimated by E/E' ratio after exercise
      predicts development of new-onset atrial fibrillation independently of left
      atrial enlargement among elderly patients without obvious myocardial ischemia.
AB  - OBJECTIVE: To determine whether elevated left ventricular (LV) filling pressure
      estimated by raised Doppler E velocity to tissue Doppler E' velocity ratio (E/E')
      after exercise is associated with increased risk of new-onset atrial fibrillation
      (AF) in non-ischemic elderly patients. BACKGROUND: Prognostic importance of
      exercise induced LV diastolic dysfunction remains uncertain. PATIENTS AND
      METHODS: We studied 147 elderly patients (73 +/- 5 years) who underwent treadmill
      stress echocardiography. Patients with exercise induced LV wall motion
      abnormality were not included. Doppler and tissue Doppler measurements were done
      before treadmill exercise and immediately after the post-stress image
      acquisition, and E/E' ratio was measured. Raised E/E' was defined as E/E'>= 15,
      and left atrial (LA) enlargement was defined as LA volume index >= 34 ml/m(2).
      Using Cox proportional hazards regression analysis, predictor of new-onset AF was
      determined. Using Kaplan-Meier analysis, we evaluated association between raised
      post-exercise E/E' or LA enlargement with new-onset AF. RESULTS: During the
      follow-up period (median=67 months), there were 25 new-onset AF. Cox proportional
      hazards regression analysis demonstrated that male gender [hazard ratio (HR)
      3.294; p=0.0117], LA enlargement (HR 3.576; p=0.0017), and raised post-exercise
      E/E' (HR 3147; p=0.0068) were the best predictors of new-onset AF. Kaplan-Meier
      survival plot demonstrated that patients with both LA enlargement and raised post
      exercise E/E' developed new-onset AF most frequently. There was no significant
      difference in outcome between patients with isolated raised post-exercise E/E' or
      isolated LA enlargement. CONCLUSIONS: Raised E/E' ratio after exercise provides
      significant prognostic information for predicting new-onset AF in non-ischemic
      elderly patients. This prognostic value of raised post-exercise E/E' is
      independent of and incremental to the LA enlargement.

PMID- 24012434
TI  - Association of prediabetes with diffuse coronary narrowing and small-vessel
      disease.
AB  - BACKGROUND: A significant number of patients may not benefit from conventional
      techniques of myocardial revascularization due to diffuse coronary artery disease
      (CAD) or small coronary arterial sizes because of smaller arteries causing
      anastomotic technical difficulties and poor run-off. Diabetic patients have a
      more severe and diffuse coronary atherosclerosis with smaller coronary arteries
      limiting the possibility to perform a successful and complete revascularization,
      but this has not been examined in prediabetics. OBJECTIVE: To evaluate whether
      there is an association between prediabetes and the coronary arterial size.
      METHODS: We prospectively studied 168 consecutive patients with CAD and 172
      patients with normal coronary artery anatomy (NCA). Patients were divided into
      three groups according to hemoglobin (Hb) A1c levels as "normal," "prediabetic,"
      and "diabetic" groups, and the coronary artery sizes and Gensini scores were
      analyzed. RESULTS: There were 78 female patients and 90 male patients in the CAD
      group, and 87 female patients and 85 male patients in the NCA group. There was a
      statistically significant difference in distal and proximal total coronary
      arterial size among the CAD and NCA groups for both genders. There was a positive
      correlation between the HbA1c subgroups and Gensini score (Spearman's rho: 0.489,
      p<0.001 in female group; Spearman's rho: 0.252 p=0.016 in male group).
      CONCLUSION: We found that prediabetic patients have a smaller coronary size and
      diffuse coronary narrowing for both genders, particularly in distal coronary
      arterial tree of left anterior descending coronary artery. The early detection of
      prediabetes in daily cardiology practice may provide more appropriate coronary
      lesion for percutaneous or surgical revascularization.

PMID- 24012435
TI  - The effect of Platelet Lysate on osteoblast proliferation associated with a
      transient increase of the inflammatory response in bone regeneration.
AB  - Platelet Lysate (PL) contains a cocktail of growth factors and cytokines, which
      actively participates in tissue repair and its clinical application has been
      broadly described. The aim of this study was to assess the regenerative potential
      of PL for bone repair. We demonstrated that PL stimulation induces a transient
      increase of the inflammatory response in quiescent human osteoblasts, via NF-kB
      activation, COX-2 induction, PGE2 production and secretion of pro-inflammatory
      cytokines. Furthermore, we showed that long-term PL stimulation enhances
      proliferation of actively replicating osteoblasts, without affecting their
      differentiation potential, along with changes of cell morphology, resulting in
      increased cell density at confluence. In confluent resting osteoblasts, PL
      treatment induced resumption of proliferation, change in cell morphology and
      increase of cell density at confluence. A burst of PL treatment (24-h) was
      sufficient to trigger such processes in both conditions. These results correlated
      with up-regulation of the proliferative and survival pathways ERKs and Akt and
      with cell cycle re-activation via induction of CyclinD1 and phosphorylation of
      Rb, following PL stimulation. Our findings demonstrate that PL treatment results
      in activation and expansion of resting osteoblasts, without affecting their
      differentiation potential. Therefore PL represents a good therapeutic candidate
      in regenerative medicine for bone repair.

PMID- 24012436
TI  - Clinical research on the incision line selection of video-assisted thoracoscopic
      wedge resection of the lung.
AB  - OBJECTIVE: To compare the clinical efficacy of video-assisted thoracoscopic
      direct lung wedge resection (banana peel method) with that of the opposite
      resection line (traditional method). METHODS: Review and analysis of 83 cases of
      video-assisted thoracoscopic wedge resections of lung operations from February
      2007 to September 2011. All of the patients were divided into two groups, as
      follows: Group A: wedge resection of the lung by the opposite resection line
      (traditional method), 41 cases; Group B: direct lung wedge resection (banana peel
      method), 42 cases. Both of the groups received video-assisted thoracic surgery.
      The postoperative follow-up period was 1-6 months, with an average of 3.6 months.
      The operating conditions (including operation time, transoperative bleeding
      volume, number of transoperative sutures added, postoperative time to extubation,
      surgery cost, number of suturing instruments used for incising with the endoscope
      and the cost of hospitalisation), atelectasis conditions 1 month after the
      operation and the decreasing lung function conditions were compared between
      groups. RESULTS: Group B's operative time was (62 +/- 10) min, significantly less
      than Group A's (81 +/- 16) min (P < 0.05). The amount of bleeding in Group B was
      (52 +/- 17) ml, which was also significantly less than that of Group A, at (74 +/
      21) ml (P < 0.05). Compared to Group A, Group B had significantly (P < 0.05)
      fewer manual sutures and shorter postoperative extubation times. The cost of
      surgery and number of endoscopic staplers used during the operation in Group B
      were significantly larger than in Group A; however, the total hospital costs did
      not differ between the two groups (P > 0.05). Neither group had any cases of
      atelectasis based on chest X-ray films taken 1 month after the operation, and no
      difference was found in the groups' decreased lung functions. CONCLUSIONS: The
      video-assisted thoracoscopic direct lung wedge resection (banana peel method) can
      shorten the operative time, lessen the surgical trauma, reduce the number of
      additional manual sutures required, and make for an overall more convenient
      operation, compared to wedge resection of lung by opposite resection line
      (traditional method). Although operation costs have increased, the total hospital
      costs have not. Thus, the better choice for video-assisted thoracoscopic lung
      wedge resections involves the use of direct lung wedge resection.

PMID- 24012437
TI  - The economic impact of individually packaged screws.
AB  - BACKGROUND: Trends in orthopaedic surgery have seen a migration towards using
      individually packaged screws (IPS). The manufacturers claim IPS improves
      sterility, traceability, and avoids the effects of repeated sterilisation. In
      recent times there has been increasing pressure on the NHS to be more cost
      efficient. Challenging decisions must be made to make cost-efficient choices
      without comprising the quality of care provided. AIM: This study investigates the
      cost-benefit of IPS compared to the conventional screw rack stored screws (SRSS).
      METHODS: A single-centred observational study was carried out in a district
      general hospital between February and March 2013. One-hundred and forty-seven
      screws were requested intra-operatively and the screw acquisition time was
      measured with a digital handheld timer. Screw acquisition time was defined as the
      time taken from the initial verbal request to when the screw was mounted ready
      for use. The screws were categorised into two groups: SRSS and IPS. RESULTS: The
      mean screw acquisition time for the SRSS group (n = 94) was 6.6 s (S.D +/- 2.5).
      The mean screw acquisition time for the IPS group (n = 53) was 102.1 s (S.D +/-
      25.7). The mean difference between SRSS and IPS was 96 s (95%CI 90.3-100.8; p <
      0.001). CONCLUSION: Our study suggests that the use of IPS significantly (p <
      0.001) increases the operation duration and costs compared to SRSS. Based on
      ankle ORIF procedures alone, the use of IPS could potentially increase department
      spending by approximately L76,680 per year.

PMID- 24012438
TI  - A Canadian perspective on documentary film: Drug Addict.
AB  - BACKGROUND: In 1948 the first National Film Board (NFB) documentary in Canada
      about illegal drugs, trafficking, and addiction was produced. The documentary is
      titled Drug Addict, and was directed by Robert Anderson. This paper provides a
      socio-historical context for the documentary Drug Addict. Viewing the film
      through the lens of Canadian history gives readers a better context to understand
      the claims and representations in the film about law enforcement, people who use
      illegal drugs and treatment. METHODS: To examine Drug Addict, a socio-historical
      analysis and case study were conducted. This project's qualitative methodological
      framework is consistent with its critical theoretical perspective, drawing from
      Stuart Hall's perspectives on visual and textual representation and cultural
      criminology. RESULTS: Drug Addict is a significant documentary because it
      provides insight into early foundational law enforcement discourses and practices
      about illegal drugs, addiction, and treatment, including obstacles to drug
      substitution and maintenance programs. It also highlights the emergence of
      psychiatry as a new knowledge producer in the area of drug treatment. The film
      also transmits ideas about the criminal nature of addicts and the need for
      punitive criminal justice control. CONCLUSION: Drug Addict captures some past and
      contemporary tensions related to Canadian drug policy. The film also provides
      another lens to understand some of the foundational frameworks of Canadian drug
      policy such as the dominance of criminal justice, and its practices of knowledge
      production, the resistance espoused by institutions to diverse models of
      treatment such as drug maintenance programs, and the power of visual
      representation.

PMID- 24012439
TI  - A critical role for interleukin-1beta in the progression of autoimmune diseases.
AB  - Interleukin-1beta (IL-1beta) belongs to IL-1 family and is a potent pro
      inflammatory cytokine. It is known to be also involved in a variety of cellular
      activities, including cell proliferation, differentiation and apoptosis. In
      addition to its pathophysiologic role in host protection, IL-1beta promotes the
      progression of a number of autoimmune diseases. Most of such diseases can be
      controlled by anti-IL-1beta treatment. This review discusses the contribution of
      IL-1beta to the course of autoimmune diseases, such as rheumatic diseases,
      uveitis, autoimmune thyroid diseases (AITD), insulin-dependent diabetes mellitus
      (IDDM), autoimmune inner ear disease (AIED), multiple sclerosis (MS),
      myocarditis, hepatitis and kidney diseases. The critical involvement of IL-1beta
      in the pathogenesis of autoimmune diseases provides targets for developing
      therapeutic treatment. 

PMID- 24012441
TI  - Postmenopausal female with abdominal pain.

PMID- 24012442
TI  - Middle-aged man with left neck pain and swelling.
AB  - BACKGROUND: Disorders of the salivary glands can be evaluated by bedside
      ultrasonography and should be considered in patients presenting with
      undifferentiated neck swelling. OBJECTIVE: Our aim was to describe the
      sonographic findings present in sialolithiasis and sialadenitis. CASE REPORT: A
      61-year-old man presented to the emergency department with 2 days of neck
      swelling. Initial evaluation included a bedside ultrasound that demonstrated
      sialolithiasis, which was later confirmed by computed tomography. CONCLUSIONS:
      Bedside ultrasound can be a useful imaging modality in the evaluation of the
      patient with neck swelling.

PMID- 24012440
TI  - Generation of a novel Cr2 gene allele by homologous recombination that abrogates
      production of Cr2 but is sufficient for expression of Cr1.
AB  - The enhancing effects of the complement system for humoral immunity have
      primarily focused upon the recognition of complement-bound foreign antigens by a
      co-receptor complex of the antigen-specific B cell receptor (BCR) and complement
      receptor 2 (Cr2). In vivo experiments using Cr2 gene deficient mice (which lack
      the expression of both the Cr1 and Cr2 proteins) do demonstrate depressed humoral
      responses to immunization but cannot be used to define specific contributions of
      the singular Cr1 or Cr2 proteins on B cell functions. To study the effect of a
      Cr2 deficiency in a Cr1 sufficient environment we created a mouse line in which
      the alternative splice site required for the expression of the Cr2 isoform was
      removed. This mouse line, Cr2KO, still expressed Cr1 on B cells but was deficient
      for the full length Cr2 protein. Surprisingly a new alternative splice within the
      Cr2 gene created a truncated product that encoded a novel protein termed iCr2
      that was expressed on the surface of the cells. The Cr2KO mouse thus provides a
      new model system for the analysis of Cr1 and Cr2 functions in the immune response
      of the mouse. 

PMID- 24012443
TI  - [Livedo reticularis secondary to amantadine in a patient with Parkinson disease].

PMID- 24012444
TI  - [Abnormalities of carbohydrate metabolism in acromegaly].
AB  - BACKGROUND AND OBJECTIVE: Carbohydrate metabolism (CHM) is impaired in over 50%
      of acromegalic patients. Natural history of acromegaly and treatment modalities
      may impact in a different way on CHM. We assessed CHM alterations in acromegaly
      and their relationship with clinical features and treatment options. PATIENTS AND
      METHOD: Retrospective study with 55 patients with acromegaly. Age, sex, body mass
      index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the
      presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were
      analyzed before and after surgery or medical treatment. RESULTS: There were 30
      men and 25 women. Mean age was 50 +/- 17 years and mean BMI was 27.9 +/- 3.8
      Kg/m(2). Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In
      diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels
      between IFG/DM and patients without CHM impairment. However, IFG/DM patients had
      macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin
      (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues
      from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction
      of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant
      group, insulin and/or oral agents had to be lowered. CONCLUSIONS: Up to 50% of
      patients with active acromegaly have CHM impairment which correlates with tumor
      size. Only pegvisomant is associated with significant improvement in glycemic
      control and a reduction in hypoglycemic treatment.

PMID- 24012446
TI  - [Erythropoiesis-stimulating agents in congestive heart failure patients].
AB  - Congestive heart failure is a disease of high incidence and prevalence in the
      elderly. Anemia is associated with an increased mortality in these patients. This
      article reviews the cumulated evidence about the use of erythropoiesis
      stimulating agents in congestive heart failure patients. Although some
      improvement in quality of life has been shown, it has not been found any
      decrement on mortality and, as a result, together with the high drug cost, it is
      not recommended the use of this kind of drugs in heart failure patients.

PMID- 24012445
TI  - [Infections due to human immunodeficiency virus type 2 and human T-lymphotropic
      viruses in Spain].

PMID- 24012447
TI  - [Significance of an adequate design in genetic diagnosis protocols].

PMID- 24012448
TI  - Can clitoris-conserving surgery for early vulvar cancer improve the outcome in
      terms of quality of life and sexual sensation?
AB  - OBJECTIVES: Vulvar carcinomas (VC) and vulvar in situ cancers (VCIS) are rare
      genital malignancies. Total vulvectomy as the standard of care has been replaced
      by local excision during the early stages of the disease. We studied whether
      conservation of the clitoris in vulvar surgery has a positive effect on either
      the quality of life (QoL) or the sexual sensation of the patient. STUDY DESIGN:
      In a retrospective study, patients with and without clitoris-sparing surgery were
      interviewed using the Female Sexual Function Index questionnaire (FSFI) and the
      Short Form 12((r)) questionnaire (SF-12). The frequencies of high and low levels
      and the medians were compared using the Cox-Mantel, Chi(2) and Fisher's exact
      tests. RESULTS: We identified 24 patients who had surgery in our department for
      VCIS or VC stage I/II, between 2006 and 2008. Ten of these patients required
      total inguinal lymphadenectomies and another five required sentinel node
      biopsies. In twelve patients, the clitoris had been spared, whereas in the
      remaining twelve, the clitoris had needed to be removed. These groups did not
      differ in terms of tumor size, stage, type of surgery or age of the patients. The
      evaluation of the SF-12 indicated high satisfaction in the physical scores for
      33% of patients with clitoris-sparing surgery vs. 67% after clitoris resection
      (n.s.). For the mental domain, the rates were 58% and 67% (n.s.), respectively.
      In the FSFI, both groups showed comparable values <18 (n = 7) and >18 (n = 5) in
      sexual sensation. CONCLUSION: Reducing the surgical resection is oncologically
      acceptable, but improvement in the patients' quality of life or sexual sensation
      is not achieved solely by conserving the clitoris.

PMID- 24012449
TI  - Fresh blastocyst transfer as a clinical approach to overcome the detrimental
      effect of progesterone elevation at hCG triggering: a strategy in the context of
      the Italian law.
AB  - OBJECTIVE: To retrospectively evaluate whether fresh day-5 embryo transfer could
      overcomes the detrimental effect of subtle progesterone elevations at hCG
      administration on pregnancy outcomes in women undergoing ovarian hyperstimulation
      for IVF/ICSI cycles. STUDY DESIGN: Retrospective study of 204 infertile patients
      aged 23-44 years who underwent IVF/ICSI treatment and fresh blastocyst transfer
      under the Italian law (embryos cryopreservation cannot be planned in advance).
      Women were divided into those with a progesterone level <1.5 ng/ml and those with
      a progesterone concentration >= 1.5 ng/ml at hCG triggering. The clinical
      pregnancy rate (CPR) after blastocyst transfer was the primary outcome. RESULTS:
      Age, body mass index (BMI), antral follicle count, anti-Mullerian hormone (AMH)
      and FSH values, mean number of stimulation days, ratio of GnRH agonist and
      antagonist cycles and total dose of gonadotrophins administered did not differ
      between the two groups. Serum estradiol and number of retrieved oocytes were
      significantly increased in the group with elevated progesterone and a
      significantly higher number of oocytes was used in this group. Fertilization
      rate, percentage of top quality embryos, and number of transferred blastocysts
      were similar in the two groups. The CPR was significantly higher in women with
      progesterone levels <1.5 ng/ml at hCG (50%) compared with women with progesterone
      concentration >= 1.5 ng/ml (33.3%) (odds ratio = 2.00, 95% confidence interval
      1.07-3.75). CONCLUSIONS: A fresh blastocyst transfer does not completely overcome
      the detrimental effect of progesterone rise at hCG on IVF/ICSI pregnancy
      outcomes.

PMID- 24012450
TI  - Monoclonal antibody 26 cross-reactive with beta2-glycoprotein I affects human
      trophoblast invasion in vitro.
AB  - OBJECTIVE: Monoclonal antibody 26 (MAb 26) raised against tetanus toxoid has
      documented cross-reactivity with beta2-glycoprotein I. Passive introduction of
      this antibody in mice results in an antiphospholipid syndrome-like condition. We
      investigated the effects of MAb 26 on first trimester human trophoblast in vitro.
      STUDY DESIGN: Binding of MAb 26 to placental tissue trophoblast, isolated
      cytotrophoblast and HTR-8/SVneo cells was analyzed by immunohisto(cyto)chemistry.
      Possible effects on cell invasion in vitro were assessed by Matrigel assay.
      Effects on cell viability were assessed by MTT test. A possibility that MAb 26
      induces change in levels of effector molecules important for cell invasion was
      investigated. Integrin subunits alpha1, alpha5 and beta1, and galectin-1, were
      analyzed by qPCR and Western blot. Metalloproteinases -2 and -9 were assessed by
      gelatin zymography. RESULTS: Immunohisto(cyto)chemistry showed binding of MAb 26
      to placental tissue trophoblast, isolated cytotrophoblast and HTR-8/SVneo cells.
      The antibody had a significant inhibitory effect on cell invasion by both
      isolated cytotrophoblast and HTR-8/SVneo. The antibody induced significant
      decrease in protein levels of metalloproteinases, integrin subunit alpha1 and
      galectin-1. Cell viability was not affected. CONCLUSION: MAb 26 reduces
      trophoblast invasion in vitro through decreased levels of metalloproteinases-2
      and -9, integrin alpha1 and galectin-1.

PMID- 24012451
TI  - Prediction of spontaneous preterm delivery in the first trimester of pregnancy.
AB  - OBJECTIVE: To develop a model for predicting premature delivery before 37 weeks'
      gestation based on maternal factors, obstetric history and biomarkers in the
      first trimester of pregnancy. STUDY DESIGN: Cohort study based on data collected
      prospectively between 1 January 2000 and 30 November 2011. Multivariate logistic
      regression was used to construct a model of the risk of premature delivery.
      RESULTS: 31,834 pregnancies were included, of which 1188 cases were spontaneous
      premature deliveries before 37 weeks (3.7%). We built a predictive model based on
      maternal age, body mass index, smoking status and previous obstetric history.
      This could identify 23.3% of premature deliveries in our study population, with a
      false positive rate of 10%. In the group of patients who had already had at least
      one pregnancy at or beyond 16 weeks, the detection level increased to 29.7%. The
      positive predictive value was 7.4 and 7.3% respectively, while negative
      predictive value was 97.2 and 97.9%. CONCLUSIONS: Predicting preterm delivery on
      the basis of maternal characteristics and obstetric history needs to be further
      improved. PAPP-A levels and ultrasonographic measurement of cervical length could
      not be integrated in the model but require further investigations.

PMID- 24012452
TI  - Comparison of the utility of whole-body MRI with and without contrast-enhanced
      Quick 3D and double RF fat suppression techniques, conventional whole-body MRI,
      PET/CT and conventional examination for assessment of recurrence in NSCLC
      patients.
AB  - PURPOSE: The purpose of this study was to compare diagnostic capabilities for
      assessment of recurrence in non-small cell lung cancer (NSCLC) patients by
      contrast-enhanced whole-body MRI (CE-WB-MRI) with and without CE-Quick 3D and
      double RF fat suppression technique (DFS), FDG-PET/CT and conventional
      radiological examinations. MATERIALS AND METHODS: A total of 134 pathologically
      proven and completely resected NSCLC patients (78 males, 56 females; mean age: 72
      years) underwent FDG-PET/CT, CE-WB-MRI with and without Quick 3D and DFS at 3T as
      well as conventional radiological examinations. The probability of recurrence was
      assessed with a 5-point scoring system on a per-patient basis, and final
      diagnosis was made by consensus between two readers. The capability for overall
      recurrence assessment by all the methods was compared by means of ROC analysis
      and their sensitivity, specificity and accuracy by means of McNemar's test.
      RESULTS: Although areas under the curve did not show any significant differences,
      specificity (100%) and accuracy (95.5%) of CE-WB-MRI with CE-Quick 3D and DFS
      were significantly higher than those of FDG-PET/CT (specificity: 93.6%, p=0.02;
      accuracy: 89.6%, p=0.01) and conventional radiological examinations (specificity:
      92.7%, p=0.01; accuracy: 91.0%, p=0.03). In addition, specificity of CE-WB-MRI
      without CE-Quick 3D and DFS (100%) was significantly higher than that of FDG
      PET/CT (p=0.02) and conventional radiological examinations (p=0.01). CONCLUSION:
      Specificity and accuracy of CE-WB-MRI with CE-Quick 3D and DFS for assessment of
      recurrence in NSCLC patients are at least as high as, or higher than those of
      others.

PMID- 24012453
TI  - Combined treatment of subacute and acute synthetic and venous bypass-graft
      occlusions with percutaneous mechanical thrombectomy and thrombolysis.
AB  - INTRODUCTION: Percutaneous mechanical thrombectomy (PMT) is a third choice of
      treatment for acute arterial occlusions, in addition to thrombolysis and surgical
      thrombectomy. The aim of this retrospective study was to compare the combined
      treatment of PMT and local thrombolysis with thrombolysis therapy alone.
      MATERIALS AND METHODS: Sixty-nine patients with acute (<14 days [n = 35]) or
      subacute (14-42 days [n = 34]) femoropopliteal bypass occlusions were treated
      with PMT combined with thrombolysis. Seventy-two patients with acute [n=40] or
      subacute [n = 32] femoropopliteal bypass occlusions were treated with
      thrombolysis alone. The thrombolysis in myocardial infarction (TIMI)
      classification was used to assess the bypass occlusion. Local thrombolysis time
      and dosage, reopening time, time in the intensive care unit, necessary surgical
      re-interventions, and clinical outcome were compared between the 2 groups.
      RESULTS: The TIMI scores were significantly higher in the PMT plus thrombolysis
      group than in the thrombolysis group (acute occlusions 1188 versus 935, p<0.001;
      subacute occlusions 935 versus 605, p<0.001). The total urokinase dosage, the
      total hours of thrombolysis, time in the intensive care unit, and total hospital
      stay in the acute PMT plus thrombolysis group were significantly lesser than
      those in the thrombolysis group. After 24h of treatment, the ankle-brachial index
      improved in all groups (p<0.001): in the acute and subacute PMT plus thrombolysis
      group to 0.63 +/- 0.14 and 0.43 +/- 0.08, respectively; and in the acute and
      subacute thrombolysis group to 0.51 +/- 0.11 and 0.41 +/- 0.04, respectively.
      CONCLUSIONS: PMT combined with thrombolysis is a safe and very effective therapy
      for acute and subacute femoropopliteal bypass occlusions compared to treatment
      with thrombolysis alone.

PMID- 24012454
TI  - Detection of active bile leak with Gd-EOB-DTPA enhanced MR cholangiography:
      comparison of 20-25 min delayed and 60-180 min delayed images.
AB  - OBJECTIVES: The purpose of this study was to assess the value of contrast
      enhanced magnetic resonance cholangiography (MRC) performed in different time
      delays after injection of gadoxetic acid disodium (Gd-EOB-DTPA) for the diagnosis
      of active bile leak. METHODS: This retrospective analysis included Gd-EOB-DTPA
      enhanced MR images of 34 patients suspected of bile leak. Images were acquired 20
      25 min after Gd-EOB-DTPA injection. If there was inadequate contrast in the bile
      ducts then delayed images after 60-90 min and 150-180 min were obtained. Results
      were correlated with intraoperative findings, ERCP results, clinical data,
      laboratory tests, and follow-up examinations. RESULTS: Gd-EOB-DTPA enhanced MRC
      yielded an overall sensitivity of 96.4%, specificity of 100% and accuracy of
      97.1% for the diagnosis of an active bile leak. The sensitivity of 20-25 min
      delayed MR images was 42.9%, of combined 20-25 min and 60-90 min delayed images
      was 92.9% and of combined 20-25 min, 60-90 min and 150-180 min delayed images was
      96.4%. CONCLUSIONS: Gd-EOB-DTPA enhanced MRC utilizing delayed phase images was
      effective for detecting the presence and location of active bile leaks. The
      images acquired 60-180 min post-injection enabled identification of bile leaks
      even in patients with a dilated biliary system or moderate liver dysfunction.

PMID- 24012455
TI  - Clinical significance of long intergenic noncoding RNA-p21 in colorectal cancer.
AB  - BACKGROUND: Long intergenic noncoding RNAs (lincRNAs) have been shown to be novel
      regulators for both transcription and posttranscriptional/translation. One of
      them, lincRNA-p21, was regulated by p53 and contributed to apoptosis in mouse
      embryonic fibroblasts. However, the impact of such regulation on colorectal
      cancer (CRC) remains to be determined. METHODS: Total RNA was extracted from CRC
      cell lines and snap fresh frozen CRC samples from 2 CRC patient cohorts. The
      expression of lincRNA-p21 was quantified by quantitative real-time polymerase
      chain reaction analysis. RESULTS: We discovered that the expression level of
      lincRNA-p21 was increased by elevated wild-type p53 induced by nutlin-3 in HCT
      116 colon cancer cells. The expression level of lincRNA-p21 was significantly (P
      = .0208) lower in CRC tumor tissue when compared with the paired normal tissue
      from the same patient. There was no significant correlation of lincRNA-p21 with
      p53 status (wild-type vs. mutant). Tumors in the rectum showed a higher level of
      lincRNA-p21 than tumors in the colon (P = .00005). In addition, lincRNA-p21 in
      patients with stage III tumors was significantly higher than in those with stage
      I tumors (P = .007). Elevated levels of lincRNA-p21 were significantly associated
      with higher pT (P = .037 between pT 2 and 3) and vascular invasion (P = .017).
      CONCLUSIONS: These results indicate that lincRNA-p21 may contribute to CRC
      disease progression.

PMID- 24012456
TI  - Prognostic value of the combination of circulating tumor cells plus KRAS in
      patients with metastatic colorectal cancer treated with chemotherapy plus
      bevacizumab.
AB  - OBJECTIVE: Circulating tumor cells (CTCs) and v-Ki-ras2 Kirsten rat sarcoma viral
      oncogene homolog (KRAS) status were identified as prognostic factors for
      progression-free survival (PFS) and overall survival (OS) in patients with
      metastatic colorectal cancer treated with chemotherapy and bevacizumab in
      analyses of the MACRO (Maintenance Treatment in Advanced Colorectal Cancer)
      trial. In this post hoc analysis of the MACRO trial, the potential additive
      effect of these 2 factors on patient outcomes was explored. METHODS: A total of
      158 of the 480 patients involved in the MACRO trial were included in the
      biological marker substudy. CTC isolation and enumeration were centralized and
      performed using the CellSearch System (Veridex LLC, Raritan, NJ) in 7.5 mL of
      whole blood. Evaluation of KRAS status was performed retrospectively by the
      standard method used at each center. PFS and OS were analyzed by the Kaplan-Meier
      method according to CTC count and KRAS status. RESULTS: Patients with < 3 CTC per
      7.5 mL blood at baseline and KRAS wild-type tumors had a median PFS of 14.2
      months compared with 6.2 months in patients with >= 3 CTCs and KRAS mutated
      tumors (P < .0001; hazard ratio, 3.0; 95% confidence interval, 1.8-5.2). Similar
      findings were observed for OS (28.9 and 13.7 months, respectively, P = .0004;
      hazard ratio 2.8; 95% confidence interval, 1.6-4.9). Multivariate analyses showed
      that CTC count >= 3 and KRAS status were the only independent prognostic factors
      for both PFS and OS. CONCLUSIONS: This post hoc analysis showed that CTC count
      and KRAS status were independent prognostic factors for outcomes in patients with
      metastatic colorectal cancer treated with bevacizumab +/- chemotherapy. These
      factors should be taken into account in the design of future phase III trials.

PMID- 24012457
TI  - Novel 3-nitro-1H-1,2,4-triazole-based piperazines and 2-amino-1,3-benzothiazoles
      as antichagasic agents.
AB  - We have previously shown that 3-nitro-1H-1,2,4-triazole-based amines demonstrate
      significant trypanocidal activity, in particular against Trypanosoma cruzi, the
      causative parasite of Chagas disease. In the present work we further expanded our
      research by evaluating in vitro the trypanocidal activity of nitrotriazole-based
      piperazines and nitrotriazole-based 2-amino-1,3-benzothiazoles to establish
      additional SARs. All nitrotriazole-based derivatives were active or moderately
      active against T. cruzi; however two of them did not fulfill the selectivity
      criteria. Five derivatives were active or moderately active against Trypanosoma
      brucei rhodesiense while one derivative was moderately active against Leishmania
      donovani. Active compounds against T. cruzi demonstrated selectivity indexes
      (toxicity to host cells/toxicity to T. cruzi amastigotes) from 117 to 1725 and 12
      of 13 compounds were up to 39-fold more potent than the reference compound
      benznidazole. Detailed SARs are discussed. 

PMID- 24012458
TI  - Morphometry of superior temporal gyrus and planum temporale in schizophrenia and
      psychotic bipolar disorder.
AB  - Structural abnormalities in temporal lobe, including the superior temporal gyrus
      (STG) and planum temporale (PT), have been reported in schizophrenia (SCZ) and
      bipolar disorder (BPD) patients. While most MRI studies have suggested gray
      matter volume and surface area reduction in temporal lobe regions, few have
      explored changes in laminar thickness in PT and STG in SCZ and BPD. ROI
      subvolumes of the STG from 94 subjects were used to yield gray matter volume,
      gray/white surface area and laminar thickness for STG and PT cortical regions.
      Morphometric analysis suggests that there may be gender and laterality effects on
      the size and shape of the PT in BPD (n=36) and SCZ (n=31) with reduced laterality
      in PT in subjects with SCZ but not in BPD. In addition, PT surface area was seen
      to be larger in males, and asymmetry in PT surface area was larger in BPD.
      Subjects with SCZ had reduced thickness and smaller asymmetry in PT volume. Thus,
      the PT probably plays a more sensitive role than the STG in structural
      abnormalities seen in SCZ. 

PMID- 24012459
TI  - Social cognition as a mediator between neurocognition and functional outcome in
      individuals at clinical high risk for psychosis.
AB  - In schizophrenia, neurocognition, social cognition and functional outcome are all
      inter-related, with social cognition mediating the impact that impaired
      neurocognition has on functional outcome. Less clear is the nature of the
      relationship between neurocognition, social cognition and functional outcome in
      individuals at clinical high risk (CHR) for psychosis. 137 CHR participants
      completed a neurocognitive test battery, a battery of social cognition tasks and
      the Social Functioning Scale. Confirmatory factor analysis showed that all social
      cognition tasks were reliable and valid measures of the latent variable. The path
      from neurocognition to functioning was statistically significant (standardized
      coefficient beta=0.22, p<0.01). The path from social cognition to functioning was
      also statistically significant (beta=0.27, p<0.05). In the mediation model the
      bootstrapping estimate revealed a nonsignificant indirect effect that was the
      association of social cognition with neurocognition and with functional outcome
      (beta=0.20, 95% CI=-0.07 to 0.52, p=0.11). However, social cognition was
      significantly associated with neurocognition (beta=0.80, p<0.001) and the path
      from neurocognition to functioning was no longer significant as soon as the
      mediator (social cognition) was entered into the mediation model (beta=0.02,
      p=0.92). All of the model fit indices were very good. Unlike what has been
      observed with psychotic patients, social cognition does not seem to mediate the
      pathway from neurocognition to functional outcome when assessed with a measure of
      social attainment in individuals at CHR for psychosis. 

PMID- 24012460
TI  - Impact of physical activity on functioning of patients with first-episode
      psychosis--a 6 months prospective longitudinal study.
AB  - There has been increasing interest in studying the impact of physical activity on
      the psychological and physical well-being and functioning in patients with first
      episode psychosis. The exploration of factors which contribute to physical
      activity in psychosis may open up opportunities for improvement of functional
      outcome. The purpose of this study was to examine the association between
      physical activity level and functioning in psychosis. A total of 283 patients
      with first-episode psychosis were recruited from a specialized early intervention
      service for adult-onset psychosis (Jockey Club Early Psychosis Project) in Hong
      Kong. The level of physical activity, sociodemographics and clinical
      characteristics was assessed at study entry. Functioning was assessed at 6-months
      period. Ninety-six (33.9%) patients were categorized as physically inactive, and
      187 (66.1%) of them were physically active. Being physically inactive
      (beta=0.163, P=0.003), having more positive and negative symptoms [SAPS total
      score (beta=-0.161, P=0.005), and SANS total score (beta=-0.202, P=0.001)], and
      having lower household income (beta=0.207, P=0.001) at baseline predicted poorer
      functioning at 6months. Early intervention for psychosis should target to improve
      patients' physical activity level which may help subsequent functioning. 

PMID- 24012461
TI  - Auditory mismatch negativity and P3a in response to duration and frequency
      changes in the early stages of psychosis.
AB  - BACKGROUND: A shorter duration of untreated psychosis in patients with
      schizophrenia results in better symptomatic and functional outcomes. Therefore,
      identifying biological markers in the early stages of psychosis is an important
      step toward early detection and intervention. Mismatch negativity (MMN) and P3a
      are leading candidate biomarkers. MMN measures differ in their sensitivity to
      varying deviants. However, this has not been fully addressed in assessing the
      early stages of psychosis. In the current study, we examined MMN/P3a to duration
      deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early stages of
      psychosis. To our knowledge, this is the first study that examined both MMN/P3a
      to duration deviant (dMMN/dP3a) and frequency deviant (fMMN/fP3a) in the early
      stages of psychosis. METHODS: Participants consisted of 20 patients with first
      episode schizophrenia (FES), 21 ultra-high risk (UHR) individuals, and 22 healthy
      controls (HC). We measured dMMN/dP3a and fMMN/fP3a ERP components by means of a
      64 electrodes-cap for EEG recording, and we used two-tone auditory oddball
      paradigms with 2000 stimuli. RESULTS: The amplitude of dMMN was significantly
      reduced in FES and UHR compared to HC. The amplitude of fMMN showed no
      significant difference among the three groups. The amplitudes of dP3a and fP3a
      were significantly reduced in FES and UHR compared to HC. CONCLUSION: These
      findings suggest that dMMN may have higher sensitivity than fMMN whereas dP3a and
      fP3a may have similar sensitivity in the early stages of psychosis.

PMID- 24012462
TI  - Inferring biological evolution from fracture patterns in teeth.
AB  - It is hypothesised that specific tooth forms are adapted to resist fracture, in
      order to accommodate the high bite forces needed to secure, break down and
      consume food. Three distinct modes of tooth fracture are identified: longitudinal
      fracture, where cracks run vertically between the occlusal contact and the crown
      margin (or vice versa) within the enamel side wall; chipping fracture, where
      cracks run from near the edge of the occlusal surface to form a spall in the
      enamel at the side wall; and transverse fracture, where a crack runs horizontally
      through the entire section of the tooth to break off a fragment and expose the
      inner pulp. Explicit equations are presented expressing critical bite force for
      each fracture mode in terms of characteristic tooth dimensions. Distinctive
      transitions between modes occur depending on tooth form and size, and loading
      location and direction. Attention is focussed on the relatively flat, low-crowned
      molars of omnivorous mammals, including humans and other hominins and the
      elongate canines of living carnivores. At the same time, allusion to other tooth
      forms - the canines of the extinct sabre-tooth (Smilodon fatalis), the conical
      dentition of reptiles, and the columnar teeth of herbivores - is made to
      highlight the generality of the methodology. How these considerations impact on
      dietary behaviour in fossil and living taxa is discussed. 

PMID- 24012463
TI  - Putative anticodons in mitochondrial tRNA sidearm loops: Pocketknife tRNAs?
AB  - The hypothesis that tRNA sidearm loops bear anticodons assumes crossovers between
      anticodon and sidearms, or translation by expressed aminoacylated tRNA halves
      forming single stem-loops. Only the latter might require ribosomal adaptations.
      Drosophila mitochondrial codon usages coevolve with sidearm numbers bearing
      matching putative anticodons (comparing different codon families in one genome,
      macroevolution) and when comparing different genomes for single codon families
      (microevolution). Coevolution between Drosophila and yeast mitochondrial
      antisense tRNAs and codon usages partly confounds microevolutionary patterns for
      putative sidearm anticodons. Some tRNA sidearm loops have more than seven
      nucleotides, putative expanded anticodons potentially matching quadruplet codons
      (tetracodons, codons expanded by a fourth silent position, forming tetragenes
      (predicted by alignment analyses of Drosophila mitochondrial genomes)).
      Tetracodon numbers coevolve with expanded tRNA sidearm loops. Sidearm coevolution
      with amino acid usages and tetragenes occurs for putative anticodons in 5' and 3'
      sidearms loops (D and TPsiC loops, respectively), are stronger for the D-loop.
      Results slightly favour isolated stem-loops upon crossover hypotheses. An
      alternative hypothesis, that patterns observed for sidearm 'anticodons' do not
      imply translational activity, but recognition signals for tRNA synthetases that
      aminoacylate tRNAs, is incompatible with tetracodon/tetra-anticodon coevolution.
      Hence analyses strengthen translational hypotheses for tRNA sidearm anticodons,
      tetragenes, and antisense tRNAs. 

PMID- 24012464
TI  - Engineering soluble tobacco etch virus protease accompanies the loss of
      stability.
AB  - Tobacco etch virus protease (TEVp) is a widely used tool enzyme in biological
      studies. To improve the solubility of recombinant TEVp, three variants, including
      the double mutant (L56V/S135G), the triple mutant (T17S/N68D/I77V), and the
      quintuple mutant (T17S/L56V/N68D/I77V/S135G), have been developed, however, with
      little information on functional stability. Here we investigated the solubility
      and stability of the three TEVp mutants under different temperature and
      denaturants, and in Escherichiacoli with different cultural conditions. The
      quintuple mutant showed the highest solubility and thermostablity, and the double
      mutant was most resistant to the denaturants. The double mutant folded best in E.
      coli cells at 37 degrees C with or without the co-expressed molecular chaperones
      GroEL, GroES and GrpE. The least soluble wild type TEVp displayed better
      tolerance to denaturants than the triple and the quintuple mutants. All results
      demonstrated that TEVp is not engineered to embody the most desirable solubility
      and stability by the current mutations. 

PMID- 24012465
TI  - Compression stockings after endovenous laser ablation of the great saphenous
      vein: a prospective randomized controlled trial.
AB  - OBJECTIVES: To determine if the duration of wearing compression stockings after
      endovenous laser ablation (EVLA) of the great saphenous vein (GSV) has influence
      on pain and quality of life. METHODS: This was a prospective randomized
      controlled trial. Between December 2006 and February 2008, 109 consecutive
      patients with EVLA of the GSV were analyzed. Deep vein insufficiency, ulceration,
      more than one insufficient vein in one leg, and use of anticoagulants were
      exclusion criteria. Group A used compression stocking for 48 hours after therapy,
      group B for 7 days. Pain (visual analogue scale [VAS]) and quality of life (SF
      36) were analyzed 48 hours, 1 week, and 6 weeks after therapy. Three months after
      treatment, duplex ultrasound imaging was performed to assess occlusion rates.
      RESULTS: Both groups (group A, n = 37; group B, n = 32) where comparable at
      baseline. After 1 week, there was a significant difference in pain (VAS score 3.7
      [+/- 2.1] vs. 2.0 [+/- 1.1], p <= .001), and physical dysfunction (group A, 85.1
      [+/- 11.2] vs. group B, 95.7 [+/- 10.1]; p < .001) as well as vitality (group A,
      75 [+/- 13.0] vs. group B, 83.7 [+/- 13.4]; p = .03), all in favor of group B,
      which disappeared after 6 weeks. After 6 weeks, no significant differences in all
      endpoints were present. Duplex ultrasound imaging revealed complete GSV occlusion
      in all patients, while no cases of deep venous thrombosis had developed.
      CONCLUSIONS: Prescribing compression stockings for longer than 2 days after
      endovenous GSV ablation (without simultaneous phlebectomies) leads to reduced
      pain and improved physical function during the first week after treatment.

PMID- 24012466
TI  - Localized argyria caused by metallic silver aortic grafts: a unique adverse
      effect.
AB  - INTRODUCTION: Silver-coated grafts are designed to prevent vascular graft
      infections. Silver is a safe element but toxic effects have been reported. We
      describe two cases of possible localized argyria after silver graft implantation.
      REPORT: Two patients presented with perigraft groin collections after
      implantation of silver grafts. During reoperation, an ashen-grey necrotic
      substance was seen surrounding the grafts. The grafts were explanted and lower
      limb perfusion restored. Cultures were negative and both patients had uneventful
      recoveries. DISCUSSION: Our cases are highly suggestive of a possible unique
      adverse effect: a combination of localized silver toxicity and neutrophilic
      mediated tissue destruction.

PMID- 24012467
TI  - Defining the best management for patients with intracranial World Health
      Organization grade II meningiomas.

PMID- 24012468
TI  - The present and the future of neuroendoscopy: individualization or
      standardization?

PMID- 24012469
TI  - A lesson from a visionary pioneer of the Romanian neurosurgery: Prof. Constantin
      Arseni.

PMID- 24012470
TI  - A literature review of key molecular genetic aberrations in meningiomas: a
      potential role in the determination of radiosurgery outcomes.

PMID- 24012471
TI  - The art of basilar apex aneurysm surgery: is it sustainable in the future?

PMID- 24012472
TI  - Temsirolimus in daily use: results of a prospective multicentre noninterventional
      study of patients with metastatic kidney cancer.
AB  - BACKGROUND: Temsirolimus (TEMSR) was approved for treating advanced renal cell
      carcinoma (RCC) in 2007. Based on the data from a single phase 3 trial, it is
      recommended explicitly as first-line therapy for patients with a poor clinical
      prognosis. OBJECTIVE: The aim of this prospective multicentre trial (STARTOR) was
      to examine the effectiveness of TEMSR in daily clinical practice with a broader
      indication in the treatment of metastatic RCC. DESIGN, SETTING, AND PARTICIPANTS:
      Metastatic RCC patients treated with 25mg of TEMSR weekly were submitted to a
      prospective systematic evaluation and follow-up in 87 German centres between
      January 2008 and October 2011 using standardised procedures. OUTCOME MEASUREMENTS
      AND STATISTICAL ANALYSIS: All data were centrally analysed by an independent
      clinical research organisation. RESULTS AND LIMITATIONS: This interim analysis of
      the STARTOR study included 386 patients. The observed toxicity was tolerable, the
      median dose intensity was 91% (interquartile range: 79-100%), and the median
      treatment duration was 20.1 wk (95% confidence interval [CI], 17.0-23.3 wk).
      Clinical benefit was seen in 157 patients (40.7%); the median progression-free
      and overall survival were 4.9 mo (95% CI, 4.2-5.6) and 11.6 mo (95% CI, 9.3
      13.9), respectively. The effectiveness of TEMSR did not differ significantly in
      relation to the patient's age, histologic RCC subtype, or line of treatment. The
      major limitations were the noninterventional study design, limited information
      about Memorial Sloan-Kettering Cancer Center risk factors and detailed toxicity,
      and the lack of central radiologic review. CONCLUSIONS: TEMSR is an effective and
      largely well-tolerated treatment alternative for metastatic RCC patients in daily
      clinical practice, irrespective of the patient's age, histologic RCC subtype, or
      line of treatment.

PMID- 24012473
TI  - Keeping the patient perspective: Where are we in the world of type 1 diabetes?

PMID- 24012474
TI  - Sex influences in autoimmune disease.

PMID- 24012475
TI  - Structure-activity relationships of 44 halogenated compounds for iodotyrosine
      deiodinase-inhibitory activity.
AB  - The aim of this study was to investigate the possible influence of halogenated
      compounds on thyroid hormone metabolism via inhibition of iodotyrosine deiodinase
      (IYD) activity. The structure-activity relationships of 44 halogenated compounds
      for IYD-inhibitory activity were examined in vitro using microsomes of HEK-293 T
      cells expressing recombinant human IYD. The compounds examined were 17
      polychlorinated biphenyls (PCBs), 15 polybrominated diphenyl ethers (PBDEs), two
      agrichemicals, five antiparasitics, two pharmaceuticals and three food colorants.
      Among them, 25 halogenated phenolic compounds inhibited IYD activity at the
      concentration of 1*10(-4)M or 6*10(-4)M. Rose bengal was the most potent
      inhibitor, followed by erythrosine B, phloxine B, benzbromarone, 4'-hydroxy
      2,2',4-tribromodiphenyl ether, 4-hydroxy-2,3',3,4'-tetrabromodiphenyl ether, 4
      hydroxy-2',3,4',5,6'-pentachlorobiphenyl, 4'-hydroxy-2,2',4,5'-tetrabromodiphenyl
      ether, triclosan, and 4-hydroxy-2,2',3,4',5-pentabromodiphenyl ether. However,
      among PCBs and PBDEs without a hydroxyl group, including their methoxylated
      metabolites, none inhibited IYD activity. These results suggest that halogenated
      compounds may disturb thyroid hormone homeostasis via inhibition of IYD, and that
      the structural requirements for IYD-inhibitory activity include halogen atom and
      hydroxyl group substitution on a phenyl ring. 

PMID- 24012476
TI  - Anterior cruciate ligament rupture: Delay to diagnosis.
AB  - INTRODUCTION AND AIM: Anterior cruciate ligament (ACL) tears are common injuries.
      Despite the diagnosis being in essence a clinical one, this has often proved
      unreliable. The objective of this study was to ascertain the delay to diagnosis
      of ACL injury from initial presentation and subsequent delay to review by a knee
      specialist. METHODS: The study involved a retrospective review of 130 patient
      case notes in a consecutive series of patients undergoing primary ACL
      reconstruction. Details regarding mechanism of injury, dates of initial and
      subsequent clinic attendances and the treating health-care professional were
      recorded. Other information included dates of magnetic resonance imaging (MRI)
      scans and when a patient first saw a knee specialist. From this, delays to
      clinical or radiological diagnosis were calculated. RESULTS: There were 82 acute
      and 48 chronic ACL injuries. Overall, the initial treating practitioner made the
      diagnosis in only 25 patients, yielding a diagnostic rate of 19.2%. Diagnoses
      made on MRI scan accounted for 38.5% of cases, the remainder being diagnosed
      clinically. The mean delay to diagnosis of ACL rupture was 65 days, and only 53
      patients were diagnosed within 30 days of initial presentation. A total of 15
      patients had undergone arthroscopy, eight of which were diagnostic. The mean
      delay to consulting a soft-tissue knee surgeon was 165 days. In the acute group,
      the initial diagnostic rate was only 7.3% and the mean delay to diagnosis was 82
      days, with 29 patients diagnosed within 30 days. CONCLUSIONS: Despite 78% of the
      patients having a typical mechanism of ACL injury, and most attending acutely via
      the Emergency Department (ED), diagnosis of this common injury remains tardy.
      There has been at best only minor improvement in the diagnostic rate and delays,
      certainly of acute ACL injury, since a study in 1996. The overall clinical
      diagnostic rate remains disconcertingly low as does the delay to consulting a
      soft-tissue knee specialist.

PMID- 24012477
TI  - Single-molecule folding mechanism of an EF-hand neuronal calcium sensor.
AB  - EF-hand calcium sensors respond structurally to changes in intracellular Ca(2+)
      concentration, triggering diverse cellular responses and resulting in broad
      interactomes. Despite impressive advances in decoding their structure-function
      relationships, the folding mechanism of neuronal calcium sensors is still
      elusive. We used single-molecule optical tweezers to study the folding mechanism
      of the human neuronal calcium sensor 1 (NCS1). Two intermediate structures
      induced by Ca(2+) binding to the EF-hands were observed during refolding. The
      complete folding of the C domain is obligatory for the folding of the N domain,
      showing striking interdomain dependence. Molecular dynamics results reveal the
      atomistic details of the unfolding process and rationalize the different domain
      stabilities during mechanical unfolding. Through constant-force experiments and
      hidden Markov model analysis, the free energy landscape of the protein was
      reconstructed. Our results emphasize that NCS1 has evolved a remarkable complex
      interdomain cooperativity and a fundamentally different folding mechanism
      compared to structurally related proteins.

PMID- 24012478
TI  - Evolution of structure and mechanistic divergence in di-domain methyltransferases
      from nematode phosphocholine biosynthesis.
AB  - The phosphobase methylation pathway is the major route for supplying
      phosphocholine to phospholipid biosynthesis in plants, nematodes, and Plasmodium.
      In this pathway, phosphoethanolamine N-methyltransferase (PMT) catalyzes the
      sequential methylation of phosphoethanolamine to phosphocholine. In the PMT, one
      domain (MT1) catalyzes methylation of phosphoethanolamine to
      phosphomonomethylethanolamine and a second domain (MT2) completes the synthesis
      of phosphocholine. The X-ray crystal structures of the di-domain PMT from the
      parasitic nematode Haemonchus contortus (HcPMT1 and HcPMT2) reveal that the
      catalytic domains of these proteins are structurally distinct and allow for
      selective methylation of phosphobase substrates using different active site
      architectures. These structures also reveal changes leading to loss of function
      in the vestigial domains of the nematode PMT. Divergence of function in the two
      nematode PMTs provides two distinct antiparasitic inhibitor targets within the
      same essential metabolic pathway. The PMTs from nematodes, plants, and Plasmodium
      also highlight adaptable metabolic modularity in evolutionarily diverse
      organisms.

PMID- 24012479
TI  - High-resolution structural analysis shows how Tah1 tethers Hsp90 to the R2TP
      complex.
AB  - The ubiquitous Hsp90 chaperone participates in snoRNP and RNA polymerase assembly
      through interaction with the R2TP complex. This complex includes the proteins
      Tah1, Pih1, Rvb1, and Rvb2. Tah1 bridges Hsp90 to R2TP. Its minimal TPR domain
      includes two TPR motifs and a capping helix. We established the high-resolution
      solution structures of Tah1 free and in complex with the Hsp90 C-terminal
      peptide. The TPR fold is similar in the free and bound forms and we show
      experimentally that in addition to its solvating/stabilizing role, the capping
      helix is essential for the recognition of the Hsp90 (704)EMEEVD(709) motif. In
      addition to Lys79 and Arg83 from the carboxylate clamp, this helix bears Tyr82
      forming a pi/S-CH3 interaction with Hsp90 M(705) from the peptide 310 helix. The
      Tah1 C-terminal region is unfolded, and we demonstrate that it is essential for
      the recruitment of the Pih1 C-terminal domain and folds upon binding.

PMID- 24012480
TI  - Flow field-flow fractionation for the analysis of nanoparticles used in drug
      delivery.
AB  - Structured nanoparticles (NPs) with controlled size distribution and novel
      physicochemical features present fundamental advantages as drug delivery systems
      with respect to bulk drugs. NPs can transport and release drugs to target sites
      with high efficiency and limited side effects. Regulatory institutions such as
      the US Food and Drug Administration (FDA) and the European Commission have
      pointed out that major limitations to the real application of current
      nanotechnology lie in the lack of homogeneous, pure and well-characterized NPs,
      also because of the lack of well-assessed, robust routine methods for their
      quality control and characterization. Many properties of NPs are size-dependent,
      thus the particle size distribution (PSD) plays a fundamental role in determining
      the NP properties. At present, scanning and transmission electron microscopy
      (SEM, TEM) are among the most used techniques to size characterize NPs. Size
      exclusion chromatography (SEC) is also applied to the size separation of complex
      NP samples. SEC selectivity is, however, quite limited for very large molar mass
      analytes such as NPs, and interactions with the stationary phase can alter NP
      morphology. Flow field-flow fractionation (F4) is increasingly used as a mature
      separation method to size sort and characterize NPs in native conditions.
      Moreover, the hyphenation with light scattering (LS) methods can enhance the
      accuracy of size analysis of complex samples. In this paper, the applications of
      F4-LS to NP analysis used as drug delivery systems for their size analysis, and
      the study of stability and drug release effects are reviewed. 

PMID- 24012481
TI  - How best to diagnose and treat the small-for-gestational-age fetus.

PMID- 24012482
TI  - What to expect from expectant management in severe preeclampsia at <34 weeks
      gestation: pregnancy outcomes in developed vs developing countries.

PMID- 24012483
TI  - Fructophilic behaviour of Gordonia alkanivorans strain 1B during dibenzothiophene
      desulfurization process.
AB  - Biodesulfurization (BDS) aims at the removal of recalcitrant sulfur from fossil
      fuels at mild operating conditions with the aid of microorganisms. These
      microorganisms can remove sulfur from dibenzothiphene (DBT), a model compound, or
      other polycyclic aromatic used as sulfur source, making BDS an easy and
      environmental friendly process. Gordonia alkanivorans strain 1B has been
      described as a desulfurizing bacterium, able to desulfurize DBT to 2
      hydroxybiphenyl (2-HBP), the final product of the 4S pathway, using d-glucose as
      carbon source. However, both cell growth and desulfurization can be largely
      affected by the nutrient composition of the growth medium, due to cofactor
      requirements of many enzymes involved in the BDS biochemical pathway. In this
      study, the main goal was to investigate the influence of several sugars, as
      carbon source, on the growth and DBT desulfurization ability of G. alkanivorans
      strain 1B. The results of desulfurization tests showed that the lowest values for
      the growth rate (0.025 hour(-1)) and for the overall 2-HBP production rate (1.80
      MUm/hour) by the strain 1B were obtained in glucose grown cultures. When using
      sucrose, the growth rate increase exhibited by strain 1B led to a higher biomass
      productivity, which induced a slightly increase in the 2-HBP production rate
      (1.91 MUm/hour), conversely in terms of 2-HBP specific production rate (q2-HBP)
      the value obtained was markedly lower (0.718 MUmol/g/hour in sucrose versus 1.22
      MUmol/g/hour in glucose). When a mixture of glucose and fructose was used as
      carbon source, strain 1B reached a value of q2-HBP=1.90 MUmol/g/hour, close to
      that in fructose (q2-HBP=2.12 MUmol/g/hour). The highest values for both cell
      growth (MU=0.091 hour(-1)) and 2-HPB production (9.29MUm/hour) were obtained when
      strain 1B was desulfurizing DBT in the presence of fructose as the only carbon
      source, indicating a fructophilic behaviour by this bacterium. This fact is in
      agreement with the highest value of biomass productivity by strain 1B be in
      fructose, which resulted in a higher amount cells fulfilling the DBT
      desulfurization. The greater number of functional cells conducted to a more
      effectiveness BDS process by strain 1B, as they attained a q2-HBP about 74%
      higher than in glucose grown cultures. Moreover, this significant BDS enhancement
      can better be observed in terms of the overall 2-HBP production rate, which
      increased over 5-fold, from 1.80 MUm/hour (in glucose) to 9.29 MUm/hour (in
      fructose).

PMID- 24012484
TI  - An imprinted gene underlies postzygotic reproductive isolation in Arabidopsis
      thaliana.
AB  - Postzygotic reproductive isolation in response to interploidy hybridizations is a
      well-known phenomenon in plants that forms a major path for sympatric speciation.
      A main determinant for the failure of interploidy hybridizations is the
      endosperm, a nutritious tissue supporting embryo growth, similar to the
      functional role of the placenta in mammals. Although it has been suggested that
      deregulated imprinted genes underpin dosage sensitivity of the endosperm, the
      molecular basis for this phenomenon remained unknown. In a genetic screen for
      suppressors of triploid seed abortion, we have identified the paternally
      expressed imprinted gene ADMETOS (ADM). Here, we present evidence that increased
      dosage of ADM causes triploid seed arrest. A large body of theoretical work
      predicted that deregulated imprinted genes establish the barrier to interploidy
      hybridization. Our study thus provides evidence strongly supporting this
      hypothesis and generates the molecular basis for our understanding of postzygotic
      hybridization barriers in plants.

PMID- 24012486
TI  - Intact Doxil is taken up intracellularly and released doxorubicin sequesters in
      the lysosome: evaluated by in vitro/in vivo live cell imaging.
AB  - Doxil, also known as Caelyx, is an established liposomal formulation of
      doxorubicin used for the treatment of ovarian cancer, sarcoma and multiple
      myeloma. While showing reduced doxorubicin related toxicity, Doxil does not
      greatly improve clinical outcome. To become biologically active, doxorubicin
      needs to be released from its carrier. Uptake and breakdown of the liposomal
      carrier and subsequent doxorubicin release is not fully understood and in this
      study we explored the hypothesis that Doxil is taken up by tumor cells and slowly
      degraded intracellularly. We investigated the kinetics of liposomal doxorubicin
      (Doxil) in vitro as well as in vivo by measuring cytotoxic effect, intracellular
      bioavailability and fate of the carrier and its content. To prevent fixation
      artifacts we applied live cell imaging in vitro and intravital microscopy in
      vivo. Within 8h after administration of free doxorubicin, 26% of the drug
      translocated to the nucleus and when reaching a specific concentration killed the
      cell. Unlike free doxorubicin, only 0.4% of the doxorubicin added as liposomal
      formulation entered the nucleus. Looking at the kinetics, we observed a build-up
      of nuclear doxorubicin within minutes of adding free doxorubicin. This was in
      contrast to Doxil showing slow translocation of doxorubicin to the nucleus and
      apparent accumulation in the cytoplasm. Observations made with time-lapse live
      cell imaging as well as in vivo intravital microscopy revealed the liposomal
      carrier colocalizing with doxorubicin in the cytoplasm. We also demonstrated the
      sequestering of liposomal doxorubicin in the lysosomal compartment resulting in
      limited delivery to the nucleus. This entrapment makes the bioavailable
      concentration of Doxil-delivered doxorubicin significantly lower and therefore
      ineffective as compared to free doxorubicin in killing tumor cells. 

PMID- 24012485
TI  - A conserved RhoGAP limits M phase contractility and coordinates with microtubule
      asters to confine RhoA during cytokinesis.
AB  - During animal cell cytokinesis, the spindle directs contractile ring assembly by
      activating RhoA in a narrow equatorial zone. Rapid GTPase activating protein
      (GAP)-mediated inactivation (RhoA flux) is proposed to limit RhoA zone
      dimensions. Testing the significance of RhoA flux has been hampered by the fact
      that the GAP targeting RhoA is not known. Here, we identify M phase GAP (MP-GAP)
      as the primary GAP targeting RhoA during mitosis and cytokinesis. MP-GAP
      inhibition caused excessive RhoA activation in M phase, leading to the
      uncontrolled formation of large cortical protrusions and late cytokinesis
      failure. RhoA zone width was broadened by attenuation of the centrosomal asters
      but was not affected by MP-GAP inhibition alone. Simultaneous aster attenuation
      and MP-GAP inhibition led to RhoA accumulation around the entire cell periphery.
      These results identify the major GAP restraining RhoA during cell division and
      delineate the relative contributions of RhoA flux and centrosomal asters in
      controlling RhoA zone dimensions.

PMID- 24012487
TI  - Targeted radiotherapy with tumor vascular homing trimeric GEBP11 peptide
      evaluated by multimodality imaging for gastric cancer.
AB  - Targeted radiopharmaceutical is an effective treatment for solid tumors. By
      labeling with radionuclides, targeting peptide could achieve both noninvasive
      diagnosis and targeted radionuclide therapy. In order to evaluate the potential
      applicability of GEBP11 peptides in diagnosis and radiotherapy of gastric cancer,
      in this study, iodine 131 labeled GEBP11 peptides, including a novel bifid
      PEGlylated GEBP11 trimer and its corresponding monomer, were developed. The
      clinical potential of GEBP11 peptides, such as tumor binding affinity and
      antitumor efficacy was demonstrated and assessed with multimodality imaging
      methods. Cerenkov and SPECT imaging showed higher tumor uptake for (131)I-2PEG
      (GEBP11)3 (P<0.05, day 1; P<0.01, day 2; vs. monomer). Biodistribution studies
      indicated higher tumor accumulation and better T/NT of (131)I-2PEG-(GEBP11)3.
      Bioluminescence imaging exhibited a significant tumor growth suppression in
      (131)I-2PEG-(GEBP11)3 treated group (P<0.001 vs. control; P<0.01 vs. monomer).
      After treatment with (131)I-2PEG-(GEBP11)3, the tumor volume and vasculature
      decreased significantly, and the survival time was prolonged to 75.5days.
      Meanwhile, no significant hepatic or renal toxicity was observed with (131)I-2PEG
      (GEBP11)3 administered. In conclusion, (131)I-2PEG-(GEBP11)3 could be a promising
      candidate for peptide-based targeting therapy of gastric cancer. 2PEG-(GEBP11)3
      might be a potential drug delivery vehicle for the antiangiogenic therapy of
      gastric cancer. 

PMID- 24012488
TI  - Human mobility and time spent at destination: impact on spatial epidemic
      spreading.
AB  - Host mobility plays a fundamental role in the spatial spread of infectious
      diseases. Previous theoretical works based on the integration of network theory
      into the metapopulation framework have shown that the heterogeneities that
      characterize real mobility networks favor the propagation of epidemics.
      Nevertheless, the studies conducted so far assumed the mobility process to be
      either Markovian (in which the memory of the origin of each traveler is lost) or
      non-Markovian with a fixed traveling time scale (in which individuals travel to a
      destination and come back at a constant rate). Available statistics however show
      that the time spent by travelers at destination is characterized by wide
      fluctuations, ranging from a single day up to several months. Such varying length
      of stay crucially affects the chance and duration of mixing events among hosts
      and may therefore have a strong impact on the spread of an emerging disease.
      Here, we present an analytical and a computational study of epidemic processes on
      a complex subpopulation network where travelers have memory of their origin and
      spend a heterogeneously distributed time interval at their destination. Through
      analytical calculations and numerical simulations we show that the heterogeneity
      of the length of stay alters the expression of the threshold between local
      outbreak and global invasion, and, moreover, it changes the epidemic behavior of
      the system in case of a global outbreak. Additionally, our theoretical framework
      allows us to study the effect of changes in the traveling behavior in response to
      the infection, by considering a scenario in which sick individuals do not leave
      their home location. Finally, we compare the results of our non-Markovian
      framework with those obtained with a classic Markovian approach and find relevant
      differences between the two, in the estimate of the epidemic invasion potential,
      as well as of the timing and the pattern of its spatial spread. These results
      highlight the importance of properly accounting for host trip duration in
      epidemic models and open the path to the inclusion of such an additional layer of
      complexity to the existing modeling approaches. 

PMID- 24012489
TI  - Leaf hydraulics II: vascularized tissues.
AB  - Current models of leaf hydration employ an Ohm's law analogy of the leaf as an
      ideal capacitor, neglecting the resistance to flow between cells, or treat the
      leaf as a plane sheet with a source of water at fixed potential filling the mid
      plane, neglecting the discrete placement of veins as well as their resistance. We
      develop a model of leaf hydration that considers the average conductance of the
      vascular network to a representative areole (region bounded by the vascular
      network), and represent the volume of tissue within the areole as a poroelastic
      composite of cells and air spaces. Solutions to the 3D flow problem are found by
      numerical simulation, and these results are then compared to 1D models with exact
      solutions for a range of leaf geometries, based on a survey of temperate woody
      plants. We then show that the hydration times given by these solutions are well
      approximated by a sum of the ideal capacitor and plane sheet times, representing
      the time for transport through the vasculature and tissue respectively. We then
      develop scaling factors relating this approximate solution to the 3D model, and
      examine the dependence of these scaling factors on leaf geometry. Finally, we
      apply a similar strategy to reduce the dimensions of the steady state problem, in
      the context of peristomatal transpiration, and consider the relation of
      transpirational gradients to equilibrium leaf water potential measurements. 

PMID- 24012490
TI  - Evolutionary branching under slow directional evolution.
AB  - Evolutionary branching is the process by which ecological interactions induce
      evolutionary diversification. In asexual populations with sufficiently rare
      mutations, evolutionary branching occurs through trait-substitution sequences
      caused by the sequential invasion of successful mutants. A necessary and
      sufficient condition for evolutionary branching of univariate traits is the
      existence of a convergence stable trait value at which selection is locally
      disruptive. Real populations, however, undergo simultaneous evolution in multiple
      traits. Here we extend conditions for evolutionary branching to bivariate trait
      spaces in which the response to disruptive selection on one trait can be
      suppressed by directional selection on another trait. To obtain analytical
      results, we study trait-substitution sequences formed by invasions that possess
      maximum likelihood. By deriving a sufficient condition for evolutionary branching
      of bivariate traits along such maximum-likelihood-invasion paths (MLIPs), we
      demonstrate the existence of a threshold ratio specifying how much disruptive
      selection in one trait direction is needed to overcome the obstruction of
      evolutionary branching caused by directional selection in the other trait
      direction. Generalizing this finding, we show that evolutionary branching of
      bivariate traits can occur along evolutionary-branching lines on which residual
      directional selection is sufficiently weak. We then present numerical analyses
      showing that our generalized condition for evolutionary branching is a good
      indicator of branching likelihood even when trait-substitution sequences do not
      follow MLIPs and when mutations are not rare. Finally, we extend the derived
      conditions for evolutionary branching to multivariate trait spaces. 

PMID- 24012491
TI  - When can a single-species, density-dependent model capture the dynamics of a
      consumer-resource system?
AB  - Single-species population models often include density-dependence
      phenomenologically in order to approximate higher order mechanisms. Here we
      consider the common scenario in which density-dependence acts via depletion of a
      renewed resource. When the response of the resource is very quick relative to
      that of the consumer, the consumer dynamics can be captured by a single-species,
      density-dependent model. Time scale separation is used to show analytically how
      the shape of the density-dependent relationship depends on the type of resource
      and the form of the functional response. Resource types of abiotic, biotic, and
      biotic with migration are considered, in combination with linear and saturating
      functional responses. In some cases, we derive familiar forms of single-species
      models, adding to the justification for their use. In other scenarios novel forms
      of density-dependence are derived, for example an abiotic resource and a
      saturating functional response can result in a nonlinear density-dependent
      relationship in the associated single-species model of the consumer. In this
      case, the per capita relationship has both concave-up and concave-down sections. 

PMID- 24012492
TI  - Anesthetic implications for robot-assisted transaxillary thyroid and parathyroid
      surgery: a report of twenty cases.
AB  - Gasless transaxillary robot-assisted endoscopic thyroid surgery has recently been
      proposed and developed in South Korea and the United States. Perianesthetic
      implications and their evolution for 20 patients scheduled to undergo this
      innovative surgical technique are presented. The anesthetic considerations focus
      on the length of surgery due to the learning curve, the risk of the ipsilateral
      arm posture, and postoperative pain evaluation and management.

PMID- 24012493
TI  - Ultrasound-guided bilateral transversus abdominis plane blocks in conjunction
      with intrathecal morphine for postcesarean analgesia.
AB  - STUDY OBJECTIVE: To determine whether transversus abdominis plane (TAP) blocks
      administered in conjunction with intrathecal morphine provided superior analgesia
      to intrathecal morphine alone. DESIGN: Randomized, double-blind, placebo
      controlled study. SETTING: Operating room of a university hospital. PATIENTS: 51
      women undergoing elective Cesarean delivery with a combined spinal-epidural
      technique that included intrathecal morphine. INTERVENTIONS: Subjects were
      randomized to receive a bilateral TAP block with 0.5% ropivacaine or 0.9% saline.
      Postoperative analgesics were administered on request and selected based on pain
      severity. MEASUREMENTS: Patients were evaluated at 2, 24, and 48 hours after the
      TAP blocks were performed. Verbal rating scale (VRS) pain scores at rest, with
      movement, and for colicky pain were recorded, as was analgesic consumption.
      Patients rated the severity of opioid side effects and their satisfaction with
      the procedure and analgesia. MAIN RESULTS: 51 subjects received TAP blocks with
      ropivacaine (n = 26) or saline (n = 25). At two hours, the ropivacaine group
      reported less pain at rest and with movement (0.5 and 1.9 vs 2.8 and 4.9 in the
      saline group [VRS scale 0 - 10]; P < 0.001) and had no requests for analgesics;
      there were several requests for analgesia in the saline group. At 24 hours, there
      was no difference in pain scores or analgesic consumption. At 48 hours, the
      ropivacaine group received more analgesics for moderate pain (P = 0.04) and the
      saline group received more analgesics for severe pain (P = 0.01). CONCLUSIONS:
      Transversus abdominis plane blocks in conjunction with intrathecal morphine
      provided superior early postcesarean analgesia to intrathecal morphine alone. By
      24 hours there was no difference in pain scores or analgesic consumption.

PMID- 24012494
TI  - Transcriptional control of skin reepithelialization.
AB  - The wound healing process is characterized by a series of overlapping phases,
      such as coagulation, inflammation, reepithelialization/granulation tissue
      generation and remodeling. It is important to obtain a deeper insight into the
      cutaneous wound repair mechanisms, in order to develop novel pharmacological
      tools for the treatment of chronic non-healing ulcers which are a frequent and
      high morbidity complication of diabetes, ischaemia, venous insufficiency, and
      other local or systemic factors. Several transcription factors, many of which
      belong to gene families, are known to play a role in cutaneous wound repair
      through the orchestration of cellular responses which promote the reconstitution
      of skin integrity. The aim of this review is to provide an updated analysis of
      the transcription factor role in the reepithelialization process, in the context
      of skin wound repair. 

PMID- 24012495
TI  - WITHDRAWN: TRIP-1 interacts with ezrin to regulate ezrin phosphorylation, cell
      protrusion formation and cell migration.
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- 24012497
TI  - LINE-1 ORF-1p functions as a novel HGF/ETS-1 signaling pathway co-activator and
      promotes the growth of MDA-MB-231 cell.
AB  - Long interspersed nucleotide element (LINE)-1 ORF-1p is encoded by the human pro
      oncogene LINE-1. It is involved in the development and progression of several
      human carcinomas, such as hepatocellular carcinoma and lung and breast cancers.
      The hepatocyte growth factor (HGF)/ETS-1 signaling pathway is involved in
      regulation of cancer cell proliferation, metastasis and invasion. The biological
      function of the interaction between LINE-1 ORF-1p and the HGF/ETS-1 signaling
      pathway in regulation of human breast cancer proliferation remains largely
      unknown. Here, we showed that LINE-1 ORF-1p enhanced ETS-1 transcriptional
      activity and increased expression of downstream genes of ETS-1. Interaction
      between ETS-1 and LINE-1 ORF-1p was identified by immunoprecipitation assays.
      LINE-1 ORF-1p modulated ETS-1 activity through cytoplasm/nucleus translocation
      and recruitment to the ETS-1 binding element in the MMP1 gene promoter. We also
      showed that LINE-1 ORF-1p promoted proliferation and anchorage-independent growth
      of MDA-MB-231 breast cancer cells. By investigating a novel role of the LINE-1
      ORF-1p in the HGF/ETS-1 signaling pathway and MDA-MB-231 cells, we demonstrated
      that LINE-1 ORF-1p may be a novel ETS-1 coactivator and molecular target for
      therapy of human triple negative breast cancer. 

PMID- 24012496
TI  - Silibinin inhibits beta-catenin/ZEB1 signaling and suppresses bladder cancer
      metastasis via dual-blocking epithelial-mesenchymal transition and stemness.
AB  - Muscle-invasive bladder cancer is associated with a high frequency of metastasis,
      and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural
      flavonoid, has been shown to exhibit pleiotropic anticancer effects in many
      cancer types, including bladder cancer. Our and other previous studies have
      demonstrated that silibinin induced apoptosis and inhibited proliferation of
      bladder cancer cells, whether silibinin could suppress bladder cancer metastasis
      has not been elucidated. In the present study, we utilized a novel highly
      metastatic T24-L cell model, and found that silibinin treatment not only resulted
      in the suppression of cell migration and invasion in vitro, but also decreased
      bladder cancer lung metastasis and prolonged animal survival in vivo.
      Mechanistically, silibinin could inhibit glycogen synthase kinase-3beta
      (GSK3beta) phosphorylation, beta-catenin nuclear translocation and
      transactivation, and ZEB1 gene transcription that subsequently regulated the
      expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to
      reverse epithelial-mesenchymal transition (EMT). On the other hand, silibinin
      inhibited ZEB1 expression and then suppressed the properties of cancer stem cells
      (CSCs), which were evidenced as decreased spheroid colony formation, side
      population, and the expression of stem cell factor CD44. Overall, this study
      reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in
      which inactivation of beta-catenin/ZEB1 signaling by silibinin leads to dual
      block of EMT and stemness. 

PMID- 24012498
TI  - Involvement of connexin43 in the EGF/EGFR signalling during self-renewal and
      differentiation of neural progenitor cells.
AB  - Neural progenitor cells (NPCs) are sensitive to epidermal growth factor (EGF),
      which is essential for their self-renewal. Recently we showed that high level of
      connexin43 (Cx43) expression and gap junctional intercellular communication
      (GJIC) are also required to maintain NPCs in a proliferative state. In this study
      the connection between EGF/EGFR signalling and Cx43 expression was investigated
      during proliferation and differentiation of cultured ReNcell VM197 human NPCs. We
      found that EGF, but not basic fibroblast growth factor (bFGF), strongly
      stimulated both Cx43 expression and GJIC in proliferating cells. This stimulatory
      effect was blocked by AG1478, a specific inhibitor for EGFR kinase. Notably,
      knockdown of Cx43 strongly inhibited the cell proliferation promoted by EGF/EGFR
      signalling. High sensitivity to EGF was still maintained in differentiated NPCs.
      Administration of EGF to differentiating cells led to a pronounced increase (9
      fold) of Cx43 expression and a re-induction of proliferation. This strong impact
      of EGF was found to correlate with a surprisingly massive 60-fold up-regulation
      of EGFR expression in differentiated cells. Our data argue for a mutual
      regulation between Cx43 expression and EGF/EGFR signalling during self-renewal
      and differentiation of NPCs. 

PMID- 24012500
TI  - Culex pipiens affected by joint infection of a mosquito iridescent virus and
      Strelkovimermis spiculatus.
AB  - Dual infections with a mosquito iridescent virus (MIV) and the mermithid
      nematode, Strelkovimermis spiculatus were recorded in natural Culex pipiens
      populations around La Plata city, Argentina. S. spiculatus was detected in 82% of
      samples that were positive for MIV infection. Dissected larvae of Cx. pipiens
      with patent MIV infection presented 42% infection with S. spiculatus. Larvae of
      Cx. pipiens exposed to MIV and S. spiculatus under laboratory conditions produced
      a high joint infection rate (82.5%) while no infection was recorded on larvae
      exposed to virus suspension only. Field and laboratory results suggest a strong
      association between S. spiculatus and MIV in natural populations of Cx. pipiens,
      in which S. spiculatus could be a mode of entry for the virus into the mosquito
      hemocele. 

PMID- 24012501
TI  - Pseudoplusia includens single nucleopolyhedrovirus: genetic diversity, phylogeny
      and hypervariability of the pif-2 gene.
AB  - The soybean looper (Pseudoplusia includens Walker, 1857) has become a major pest
      of soybean crops in Brazil. In order to determine the genetic diversity and
      phylogeny of variants of Pseudoplusia includens single nucleopolyhedrovirus
      (PsinSNPV-IA to -IG), partial sequences of the genes lef-8, lef-9, pif-2, phr and
      polh were obtained following degenerate PCR and phylogenetic trees constructed
      using maximum parsimony and Bayesian methods. The aligned sequences showed
      polymorphisms among the isolates, where the pif-2 gene was by far the most
      variable and is predicted to be under positive selection. Furthermore, some of
      the pif-2 DNA sequence mutations are predicted to result in significant amino
      acid substitutions, possibly leading to changes in oral infectivity of this
      baculovirus. Cladistic analysis revealed two closely related monophyletic groups,
      one containing PsinNPV isolates IB, IC and ID and another containing isolates IA,
      IE, IF and IG. The phylogeny of PsinSNPV in relation to 56 other baculoviruses
      was also determined from the concatenated partial LEF-8, LEF-9, PIF-2 and
      POLH/GRAN deduced amino acid sequences, using maximum-parsimony and Bayesian
      methods. This analysis clearly places PsinSNPV with the Group II
      Alphabaculovirus, where PsinSNPV is most closely related to Chrysodeixis
      chalcites NPV and Trichoplusia ni SNPV. 

PMID- 24012499
TI  - Nicotinic acetylcholine receptor antagonists alter the function and expression of
      serine racemase in PC-12 and 1321N1 cells.
AB  - Western blot analysis demonstrated that PC-12 cells express monomeric and dimeric
      forms of serine racemase (m-SR, d-SR) and that 1321N1 cells express m-SR.
      Quantitative RT-PCR and functional studies demonstrated that PC-12 cells express
      homomeric and heteromeric forms of nicotinic acetylcholine receptors (nAChR)
      while 1321N1 cells primarily express the alpha7-nAChR subtype. The effect of
      nAChR agonists and antagonists on SR activity and expression was examined by
      following concentration-dependent changes in intracellular d-Ser levels and SR
      protein expression. Incubation with (S)-nicotine increased d-Ser levels, which
      were attenuated by the alpha7-nAChR antagonist methyllycaconitine (MLA).
      Treatment of PC-12 cells with mecamylamine (MEC) produced a bimodal reduction of
      d-Ser reflecting MEC inhibition of homomeric and heteromeric nAChRs, while a
      unimodal curve was observed with 1321N1 cells, reflecting predominant expression
      of alpha7-nAChR. The nAChR subtype selectivity was probed using alpha7-nAChR
      selective inhibitors MLA and (R,S)-dehydronorketamine and alpha3beta4-nAChR
      specific inhibitor AT-1001. The compounds reduced d-Ser in PC-12 cells, but only
      MLA and (R,S)-dehydronorketamine were effective in 1321N1 cells. Incubation of PC
      12 and 1321N1 cells with (S)-nicotine, MEC and AT-1001 did not affect m-SR or d
      SR expression, while MLA and (R,S)-dehydronorketamine increased m-SR expression
      but not SR mRNA levels. Treatment with cycloheximide indicated that increased m
      SR was due to de novo protein synthesis associated with phospho-active forms of
      ERK1/2, MARCKS, Akt and rapamycin-sensitive mTOR. This effect was attenuated by
      treatment with the pharmacological inhibitors U0126, LY294002 and rapamycin,
      which selectively block the activation of ERK1/2, Akt and mTOR, respectively, and
      siRNAs directed against ERK1/2, Akt and mTOR. We propose that nAChR-associated
      changes in Ca(2+) flux affect SR activity, but not expression, and that MLA and
      (R,S)-dehydronorketamine bind to allosteric sites on the alpha7-nAChR and promote
      multiple signaling cascades that converge at mTOR to increase m-SR levels. 

PMID- 24012502
TI  - Extension and verification of the SEIR model on the 2009 influenza A (H1N1)
      pandemic in Japan.
AB  - In order to understand the evolution of the 2009 influenza A (H1N1) pandemic
      within local regions of Japan, we studied the significance of regional migration
      between these regions. For this purpose, we have employed an extended SEIR model
      to describe the immigration of infected people and the stochastic variation of
      the infectious efficiency. We then applied a data assimilation technique in order
      to study how the agreement of the simulation results with the observed data
      depends on the presence/absence of immigration and the degree of variation of the
      infectious efficiency. Reproducibility is evaluated by log-likelihood values. The
      log-likelihood does not indicate the significance of immigration. Although there
      are multiple waves in the time course of the number of reported infected
      individuals, these waves could be explained by the stochastic nature of
      infectious events. 

PMID- 24012503
TI  - Subtle interplay of stochasticity and deterministic dynamics pervades an
      evolutionary plausible genetic circuit for Bacillus subtilis competence.
AB  - Here we study the interplay of stochastic and deterministic dynamics in an
      evolutionary plausible candidate core genetic circuit for Bacillus subtilis
      competence. We find that high noise would not necessarily be detrimental to the
      circuit's ability to deliver the phenotype, due to an unexpected built-in
      robustness that we further investigate. Also, we find that seemingly subtle
      deterministic dynamical features of the regulation, unstable and stable limit
      cycles, while in the presence of biochemical noise, would result in a distinctive
      new observable in the phenotype. We conduct mathematical analyses of the system's
      stability at the fixed points and derive some general model-independent
      consequences. We also show how imperfect time-scale separation in the system
      would result in observables detrimental to the phenotype, that nature could have
      harnessed for selection. 

PMID- 24012504
TI  - Caffeic acid phenethyl ester prevents apoptotic cell death in the developing rat
      brain after pentylenetetrazole-induced status epilepticus.
AB  - Population-based studies suggest that seizure incidence is highest during the
      first year of life, and early-life seizures frequently result in the development
      of epilepsy and behavioral alterations later in life. The early-life insults like
      status epilepticus often lead to epileptogenesis, a process in which initial
      brain injury triggers cascades of molecular, cellular, and network changes and
      eventually spontaneous seizures. Caffeic acid phenethyl ester is an active
      component of propolis obtained from honeybees and has neuroprotective properties.
      The aim of this study was to investigate whether caffeic acid phenethyl ester
      exerts neuroprotective effects on the developing rat brain after status
      epilepticus. Twenty-one dams reared Wistar male rats, and 21-day-old rats were
      divided into three groups: control group, pentylenetetrazole-induced status
      epilepticus group, and caffeic acid phenethyl ester-treated group. Status
      epilepticus was induced on the first day of experiment. Caffeic acid phenethyl
      ester injections (30 mg/kg intraperitoneally) started 40 min after the tonic
      phase of status epilepticus was reached, and the injections of caffeic acid
      phenethyl ester were repeated over 5 days. Rats were sacrificed, and brain
      tissues were collected on the 5th day of experiment after the last injection of
      caffeic acid phenethyl ester. Apoptotic cell death was evaluated.
      Histopathological examination showed that caffeic acid phenethyl ester
      significantly preserved the number of neurons in the CA1, CA3, and dentate gyrus
      regions of the hippocampus and the prefrontal cortex. It also diminished
      apoptosis in the hippocampus and the prefrontal cortex. In conclusion, this
      experimental study suggests that caffeic acid phenethyl ester administration may
      be neuroprotective in status epilepticus in the developing rat brain.

PMID- 24012505
TI  - Efficacy and safety of pregabalin in refractory focal epilepsy with and without
      comorbid anxiety disorders - results of an open-label, parallel group,
      investigator-initiated, proof-of-concept study.
AB  - Anxiety disorders are prevalent in people with epilepsy and severely influence
      daily living and quality of life. Pregabalin (PGB) is licensed in Germany for the
      add on-treatment of focal epilepsy and for generalized anxiety disorder in
      adults. To our knowledge, PGB has not been studied before in patients with
      epilepsy and comorbid anxiety disorder. We included 41 adult patients with focal
      epilepsy in a monocentric, noncontrolled open-label study adding up to 600 mg of
      PGB to an antiepileptic baseline medication. Patients were allocated to two
      groups: patients with epilepsy plus anxiety disorder (EAG) and patients with
      epilepsy only (EOG). Endpoints were responder rate, seizure frequency, adverse
      events, and anxiety symptoms. The responder rate in the EAG was higher compared
      to that in the EOG (per protocol population: 9 [75.0%] vs. 2 [12.5%], p=0.001).
      Improvements in several psychological scales were found.

PMID- 24012506
TI  - Corpus callosotomy is a valuable therapeutic option for patients with Lennox
      Gastaut syndrome and medically refractory seizures.
AB  - PURPOSE: We present our experience with corpus callosotomy (CC) in a developing
      country with limited resources in patients with Lennox-Gastaut syndrome (LGS) and
      medically refractory seizures. METHODS: All patients with LGS who underwent CC
      for medically refractory epilepsy at Namazee Hospital, Shiraz University of
      Medical Sciences, Shiraz, Iran from May 2009 through March 2012 were reviewed in
      a retrospective study. Presurgical evaluation included clinical history,
      neurological examination, a 2-hour video-EEG recording, and 1.5-T MRI. Outcome
      was evaluated at 6, 12, and 24 months postoperatively. We considered the outcome
      as a success if the patients were either seizure-free or had more than 85%
      reduction in seizure frequency compared to their preoperative status. RESULTS:
      Eighteen patients (14 males and 4 females) had surgery. Overall, seizures in 11
      patients (61.1%) responded favorably one year after surgery; this figure was 6
      out of 9 patients (66.6%) two years after surgery. Seven patients (38.8%) were
      free of disabling seizures one year after CC; this figure was three out of nine
      patients (33.3%) two years after CC. Three patients (16.6%) were free of all
      seizure types one year after surgery. Ten patients (55.5%) had no postoperative
      complications of any kind. CONCLUSION: Corpus callosotomy is an effective
      palliative surgical procedure for patients with LGS with intractable seizures
      whose seizures are not amenable to focal resection. This is a feasible treatment
      option for patients, even for those in developing countries with limited
      resources.

PMID- 24012507
TI  - Delineating a new critical region for juvenile myoclonic epilepsy at the 22q11.2
      chromosome.

PMID- 24012509
TI  - Investigating higher-order cognitive functions in temporal lobe epilepsy:
      cognitive estimation.
AB  - Cognitive estimation, an ability to attribute measurements to concrete things, is
      relevant to adaptive behavior. This study evaluated cognitive estimation in
      patients with temporal lobe epilepsy (TLE) with the goal of verifying its
      relationship to temporal lobe damage and age of seizure onset. One hundred and
      eight patients with drug-resistant TLE and 51 healthy controls were evaluated
      using the Cognitive Estimation Task (CET), which requires simple and complex
      estimations providing the Total and Bizarreness scores. Different tests assessed
      reasoning, attention, executive, visuospatial, and lexical-semantic abilities.
      Patients with right TLE had earlier age of seizure onset than patients with left
      TLE and lower education than controls. Compared with controls, both patient
      groups obtained worse CET Total and Bizarreness scores, but only patients with
      right TLE were significantly impaired. Patients with seizure onset before age 12
      showed worse scores than patients with later seizure onset irrespective of the
      side of TLE. The CET Total and Bizarreness scores were predicted by age of
      seizure onset and semantic fluency; the Bizarreness score also related to
      education, chronological age, and visual attention. Results highlight the
      complexity of the cognitive pattern associated with TLE. Cognitive estimation
      deficit primarily reflects early age of seizure onset and semantic difficulties.
      An involvement of visual mental operations mediated by the right hemisphere may
      accentuate the deficit, while cognitive reserve may play a protective role. 

PMID- 24012510
TI  - Replacement of electroencephalography with polysomnography in epilepsy for
      improved assessment: need of the hour.

PMID- 24012511
TI  - Fine motor skills in children with rolandic epilepsy.
AB  - This study aimed to evaluate fine motor skills in children with rolandic epilepsy
      (RE). The research included 44 children diagnosed with typical RE and 44 controls
      matched in terms of age, gender, and level of education. Fine motor skills were
      evaluated with the Purdue Pegboard Test, and intelligence was measured with the
      Wechsler Intelligence Scale for Children. After controlling for the effect of
      intelligence on fine motor skills, the results showed that the children with RE
      did not perform as well as the controls in the PPT dominant hand, both hands, and
      assembly subtests. Epileptic focus, treatment status, type of antiepileptic
      treatment, age at the time of the first seizure, time since the last seizure, and
      total number of seizures did not affect motor skills. Rolandic epilepsy
      negatively affected fine motor skills regardless of the children's level of
      intelligence. 

PMID- 24012508
TI  - Fetal antiepileptic drug exposure: Adaptive and emotional/behavioral functioning
      at age 6years.
AB  - The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study is a
      prospective observational multicenter study in the USA and UK, which enrolled
      pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to
      2004. The study aimed to determine if differential long-term neurodevelopmental
      effects exist across four commonly used AEDs (carbamazepine, lamotrigine,
      phenytoin, and valproate). In this report, we examine fetal AED exposure effects
      on adaptive and emotional/behavioral functioning at 6years of age in 195 children
      (including three sets of twins) whose parent (in most cases, the mother)
      completed at least one of the rating scales. Adjusted mean scores for the four
      AED groups were in the low average to average range for parent ratings of
      adaptive functioning on the Adaptive Behavior Assessment System-Second Edition
      (ABAS-II) and for parent and teacher ratings of emotional/behavioral functioning
      on the Behavior Assessment System for Children (BASC). However, children whose
      mothers took valproate during pregnancy had significantly lower General Adaptive
      Composite scores than the lamotrigine and phenytoin groups. Further, a
      significant dose-related performance decline in parental ratings of adaptive
      functioning was seen for both valproate and phenytoin. Children whose mothers
      took valproate were also rated by their parents as exhibiting significantly more
      atypical behaviors and inattention than those in the lamotrigine and phenytoin
      groups. Based upon BASC parent and teacher ratings of attention span and
      hyperactivity, children of mothers who took valproate during their pregnancy were
      at a significantly greater risk for a diagnosis of ADHD. The increased likelihood
      of difficulty with adaptive functioning and ADHD with fetal valproate exposure
      should be communicated to women with epilepsy who require antiepileptic
      medication. Finally, additional research is needed to confirm these findings in
      larger prospective study samples, examine potential risks associated with other
      AEDs, better define the risks to the neonate that are associated with AEDs for
      treatment of seizures, and understand the underlying mechanisms of adverse AED
      effects on the immature brain. 

PMID- 24012512
TI  - Effects of potential probiotic Bacillus amyloliquefaciens [corrected] FPTB16 on
      systemic and cutaneous mucosal immune responses and disease resistance of catla
      (Catla catla).
AB  - Effects of dietary administration of Bacillus amyloliquefaciens FPTB16 on
      systemic and mucosal immunity and disease resistance of catla (Catla catla)
      against Edwardsiella tarda infection were evaluated in the present study. The
      laboratory maintained B. amyloliquefaciens was used to study antagonistic
      activity against fish pathogenic bacteria by agar well diffusion assay. Healthy
      catla were challenged by this bacterium for determination of its safety. For
      preparation of probiotic supplemented diet, the bacteria were added to the basal
      diet (control) at three different inclusion levels i.e., 1 * 10(9), 1 * 10(8) and
      1 * 10(7) CFU/g diet. Fish (weight 25-30 g) were fed with these diets and various
      immune parameters and disease resistance study were conducted at 4 weeks and 8
      weeks post-feeding. The bacterial antagonism study showed inhibition zone against
      E. tarda, Aeromonas hydrophila, Vibrio parahaemolyticus and V. harveyi. B.
      amyloliquefaciens was harmless to catla as neither mortalities nor morbidities
      were observed after the challenge. Study of different systemic and mucosal
      immunological parameters viz. superoxide anion production and nitric oxide
      production, myeloperoxidase content, lysozyme activity and total protein content
      showed significant enhancement (p < 0.05) in fish fed with 10(8) and 10(9) CFU/g
      B. amyloliquefaciens at both time points with the highest values observed in case
      of 10(9) CFU/g. For fish fed with 10(7) CFU/g B. amyloliquefaciens, all the
      parameters showed significant enhancement (p < 0.05) at both time points except
      the lysozyme activity of serum at 8 weeks. Diet containing 10(8) and 10(9) CFU/g
      B. amyloliquefaciens significantly enhanced (p < 0.05) the resistance of catla
      against bacterial challenge at both time points. These results collectively
      suggest that B. amyloliquefaciens is a potential probiotic species and can be
      used in aquaculture to improve health status and disease resistance with an
      optimal dietary supplementation of 10(9) CFU/g.

PMID- 24012513
TI  - Onward from Dakar: taking family planning in novel directions.

PMID- 24012514
TI  - There are some questions you may not ask in a clinic: providing contraception
      information to young people in Kenya using SMS.
AB  - OBJECTIVE: To evaluate the acceptability, information access, and potential
      behavioral impact of providing contraception information via text message on
      mobile phones to young people in Kenya. METHODS: Three methods of data collection
      were implemented during the 17-month pilot period for the Mobile for Reproductive
      Health (m4RH) program in Kenya: automatic logging of all queries to the m4RH
      system; demographic and behavior change questions sent via short message service
      protocol (SMS) to everyone who used m4RH during the pilot period; and telephone
      interviews with a subset of m4RH users. RESULTS: During the pilot period, 4817
      unique users accessed m4RH in Kenya. Of these, 82% were 29 years of age and
      younger, and 36% were male. Condom and natural family-planning information was
      accessed most frequently, although users queried all methods. One in 5 used the
      m4RH system to locate nearby clinics. Respondents liked the simple language and
      confidentiality of receiving health information via mobile phone, and reported
      increased contraceptive knowledge and use after using m4RH. CONCLUSION: Providing
      contraception information via mobile phone is an effective strategy for reaching
      young people. More research is needed to learn how to link young people to youth
      friendly services effectively.

PMID- 24012515
TI  - Osteoclastogenesis induced by CHIKV-infected fibroblast-like synoviocytes: a
      possible interplay between synoviocytes and monocytes/macrophages in CHIKV
      induced arthralgia/arthritis.
AB  - Fibroblast-like synoviocytes are known to migrate from joint to joint and are
      proposed to be one of the key players in the inflammatory cascade amplification
      in rheumatoid arthritis patients. In the recent CHIKV epidemic, patients
      developed arthritis-like syndrome and the synoviocyte is one of the suspected
      players in CHIKV-induced polyarthritis. Thus, to learn more on this syndrome, the
      responses of fibroblast-like synoviocytes to chikungunya virus (CHIKV) infection,
      and the interaction between CHIKV-infected synoviocytes and phagocytes, were
      investigated. Primary human fibroblast-like synoviocyte (HFLS) cultures were
      infected with clinical isolates of CHIKV at an MOI of 0.001pfu/cell. Data
      indicated that HFLS are permissive to CHIKV replication, generating peak titers
      of 10(5)-10(6)pfu/ml. Interestingly, CHIKV-infected HFLS cultures secreted mainly
      the mediators that are responsible for phagocytes recruitment and differentiation
      (RANKL, IL-6, IL-8 and MCP-1) but not arthritogenic mediators (TNF-alpha, IL
      1beta, MMP-1, MMP-2 or MMP-13). The interaction between CHIKV-infected
      synoviocytes and phagocytes was studied using UV-irradiated, CHIKV-infected HFLS
      supernatant. Data revealed that supernatants from CHIKV-infected HFLS cultures
      not only induced migration of primary human monocytes, but also drove
      monocytes/macrophages into osteoclast-like cells. These differentiated osteoclast
      like cells produced high levels of TNF-alpha and IL-6, principal mediators of
      arthritis. This data suggests a potential interplay between infected HFLS and
      recruiting phagocytes which may responsible for the arthralgia/arthritis in CHIKV
      infected patients.

PMID- 24012516
TI  - Characterization of a putative novel nepovirus from Aeonium sp.
AB  - A virus was isolated from potted plants of an unidentified species of Aeonium, a
      succulent ornamental very common in Southern Italy, showing chlorotic spots and
      rings on both leaf surfaces. It was successfully transmitted by sap inoculation
      to a limited range of hosts, including Nicotiana benthamiana which was used for
      ultrastructural observations and virus purification. Virus particles are
      isometric, ca. 30nm in diameter, have a single type of coat protein (CP) subunits
      54kDa in size, that encapsidate single-stranded positive-sense RNA species of
      7549 (RNA1) and 4010 (RNA2) nucleotides. A third RNA molecule 3472 nts in size
      entirely derived from RNA2 was also found. The structural organization of both
      genomic RNAs and the cytopathological features were comparable to those of
      nepoviruses. In addition, amino acid sequence comparisons of CP and the Pro-Pol
      region (a sequence containing parts of the proteinase and polymerase) with those
      of other nepoviruses showed that the Aeonium virus belongs to the subgroup A of
      the genus Nepovirus and is phylogenetically close to, but serologically distinct
      from tobacco ringspot virus (TRSV). Based on the species demarcation criteria for
      the family Secoviridae, the virus under study appears to be a novel member of the
      genus Nepovirus for which the name of Aeonium ringspot virus (AeRSV) is proposed.

PMID- 24012517
TI  - Quantification of incisal tooth wear in upper anterior teeth: conventional vs new
      method using toolmakers microscope and a three-dimensional measuring technique.
AB  - OBJECTIVES: This study aimed to quantify tooth wear in upper anterior teeth using
      a new CAD-CAM Laser scanning machine, tool maker microscope and conventional
      tooth wear index. METHODS: Fifty participants (25 males and 25 females, mean age
      = 25 +/- 4 years) were assessed for incisal tooth wear of upper anterior teeth
      using Smith and Knight clinical tooth wear index (TWI) on two occasions, the
      study baseline and 1 year later. Stone dies for each tooth were prepared and
      scanned using the CAD-CAM Laser Cercon System. Scanned images were printed and
      examined under a toolmaker microscope to quantify tooth wear and then the dies
      were directly assessed under the microscope to measure tooth wear. The Wilcoxon
      Signed Ranks Test was used to analyze the data. RESULTS: TWI scores for incisal
      edges were 0-3 and were similar at both occasions. Score 4 was not detected. Wear
      values measured by directly assessing the dies under the toolmaker microscope
      (range = 113 - 150 MUm, mean = 130 +/- 20 MUm) were significantly more than those
      measured from Cercon Digital Machine images (range=52-80 MUm, mean = 68 +/- 23
      MUm) and both showed significant differences between the two occasions.
      CONCLUSIONS: Wear progression in upper anterior teeth was effectively detected by
      directly measuring the dies or the images of dies under toolmaker microscope.
      Measuring the dies of worn dentition directly under tool maker microscope enabled
      detection of wear progression more accurately than measuring die images obtained
      with Cercon Digital Machine. Conventional method was the least sensitive for
      tooth wear quantification and was unable to identify wear progression in most
      cases.

PMID- 24012518
TI  - Can the intra-examiner variability of Little's Irregularity Index be improved
      using 3D digital models of study casts?
AB  - OBJECTIVES: To compare contact point displacement measurements, used to determine
      the Little's Irregularity Index (LII) score on study casts and digital models of
      study casts by an independent examiner. METHODS: The contact point displacement
      measurements of the six maxillary anterior labial teeth were measured on ten
      study casts using digital callipers and their associated digital models using
      Creo Parametric software on five occasions following scanning using a LAVA
      Chairside Oral Scanner (LCOS) three-dimensional (3D) intra oral scanner. Means,
      standard deviations and coefficients of variation (CoV) were determined, data
      analyses (Pearson's correlation coefficients (PCCs) and Intraclass correlation
      coefficients (ICCs)) and statistical analyses (three and two-way analyses of
      variance (ANOVAs) and Independent Sample Student's t-tests) were carried out
      (p<0.05). RESULTS: Significant positive correlations for the contact point
      displacement measurements were evident between all measurement time points for
      the study casts (r>0.978; p<0.0001 and ICC>0.910; p<0.0001) and the digital
      models (r>0.963; p<0.0001 and ICC>0.986; p<0.0001). The CoV results showed that
      the contact point displacement measurement data from the digital models was more
      reproducible than the study casts. Of the 50 Independent Sample Student's t
      tests, 21 significant increases (p<0.042) were reported in contact point
      displacement measurements <2.9 mm for the digital models compared with the study
      casts. CONCLUSION: The use of 3D digital models can improve the reliability of
      LII measurements by reducing the subjectivity associated with choosing the
      anatomic tooth contact points and the awkwardness of measuring the contact point
      displacements on study casts using a cumbersome calliper technique. CLINICAL
      SIGNIFICANCE: Intra-examiner variability in the measurement of LII is still
      evident with digital models suggesting that either improved software specifically
      aimed at the orthodontic community be identified or a new method for measuring
      anterior incisor crowding be sought.

PMID- 24012519
TI  - Atmospheric moisture effects on the testing rate and cementation seating load
      following resin-strengthening of a soda lime glass analogue for dental porcelain.
AB  - OBJECTIVES: To investigate if resin-cementation of a soda lime glass dental
      analogue could elucidate information regarding the pattern of resin-reinforcement
      when coated in an environment actively scavenged of moisture. METHODS: 192 soda
      lime disc-shaped specimens (alumina particle air abraded, hydrofluoric acid
      etched and silane coated) were randomly assigned to eight groups (n=24 per group)
      prior to resin-coating at seating loads of 5 N (Groups A-D) and 30 N (Groups E-H)
      in an environment where moisture was actively scavenged and maintained below 15
      ppm. Following one week storage the discs were tested in biaxial flexure at
      crosshead rates of 0.01, 0.1, 1 and 10mm/min. Analysis of group means was
      performed utilising a general linear model univariate analysis and post hoc all
      paired Tukey tests (P<0.05). RESULTS: The general linear model univariate
      analysis identified the mean biaxial flexure strength (BFS) was significantly
      influenced by the factors resin-cementation seating load (P<0.001) and crosshead
      speed of the applied load (P<0.001) with a significant interaction (P=0.008)
      between both factors. The linear logarithmic regression curves fitted to the
      group mean BFS data plotted against the crosshead speed highlighted significant
      differences between the pattern of resin-strengthening for the cementation loads
      and testing conditions. CONCLUSIONS: The decrease in resin-penetration expected
      within the 'resin-ceramic hybrid layer' following removal of the 30 N seating
      load was proposed as the modifying resin-strengthening parameter. These
      observations are supported by the viscoelastic and creep behaviour of resins at
      slow testing rates which becomes the dominant or determining phenomenon.

PMID- 24012520
TI  - Association between the cariogenicity of a dental microcosm biofilm and its red
      fluorescence detected by Quantitative Light-induced Fluorescence-Digital (QLF-D).
AB  - OBJECTIVE: This study evaluated whether Quantitative Light-induced Fluorescence
      Digital (QLF-D) can detect the levels of cariogenicity of dental microcosm
      biofilms by assessing the red fluorescence intensity. METHODS: Dental microcosm
      biofilms were initiated from human saliva on bovine enamel discs. Biofilms with
      various levels of cariogenicity were then grown in artificial saliva supplemented
      with sucrose at different concentrations (0.05%, 0.1%, 0.2%, and 0.5%) in 24-well
      microplates. After 10 days, fluorescence images of the biofilms were captured by
      the QLF-D to analyse the red fluorescence intensity, which was quantified as the
      red/green ratio (R/G value). The supernatant pH was also measured, as well as the
      total and aciduric bacteria counts of the collected biofilms. Mineral loss in
      enamel was also evaluated by calculating the percentage of surface microhardness
      changes (%SHC). RESULTS: The R/G values of the biofilms differed significantly
      with the sucrose concentration (p<0.0001), increasing consistently as the sucrose
      concentration increased from 0.05% (=0.91) to 0.5% (=2.56). Strong correlation
      was identified between the R/G value and the number of aciduric bacteria (r=0.83,
      p<0.0001), supernatant pH (r=-0.95, p<0.0001), and %SHC (r=0.90, p<0.0001).
      CONCLUSIONS: The red fluorescence as observed by the QLF-D was correlated with
      the cariogenic properties of dental microcosm biofilms in vitro, which indicates
      that this device can be used to detect the levels of cariogenicity of a dental
      biofilm. CLINICAL SIGNIFICANCE: The QLF-D is able to assess the cariogenic levels
      of dental plaque based on the intensity of red fluorescence.

PMID- 24012521
TI  - Expression pattern and subcellular localization of Arabidopsis purple acid
      phosphatase AtPAP9.
AB  - Purple acid phosphatase (PAP; EC 3.1.3.2) enzymes are metallophosphoesterases
      that hydrolysis phosphate ester bonds in a wide range of substrates. Twenty-nine
      PAP-encoding loci have been identified in the Arabidopsis genome, many of which
      have multiple transcript variants expressed in response to diverse environmental
      conditions. Having analyzed T-DNA insertion mutants, we have provided strong
      pieces of evidence that AtPAP9 locus encodes at least two types of transcripts,
      designated as AtPAP9-1 and AtPAP9-2. These transcript variants expressed
      distinctly during the course of growth in medium containing sufficient phosphate
      or none. Further histochemical analysis by the use of AtPAP9-1 promoter fused to
      beta-glucuronidase reporter gene indicated the expression of this gene is
      regulated in a tissue-specific manner. AtPAP9-1 was highly expressed in stipule
      and vascular tissue, particularly in response to fungal infection. Subcellular
      localization of AtPAP9-1:green fluorescent fusion protein showed that it must be
      involved in plasma membrane and cell wall adhesion. 

PMID- 24012522
TI  - Characterization and embryonic expression of four amphioxus Frizzled genes with
      important functions during early embryogenesis.
AB  - The Wnt signaling pathway plays crucial roles in the embryonic patterning of all
      metazoans. Recent studies on Wnt genes in amphioxus have shed important insights
      into the evolution of the vertebrate Wnt gene family and their functions.
      Nevertheless, the potential roles of Wnt family receptors encoded by Frizzled
      (Fz) genes in amphioxus embryonic development remain to be investigated. In the
      present study, we identified four amphioxus Fz genes-AmphiFz1/2/7, AmphiFz4,
      AmphiFz5/8, and AmphiFz9/10-and analyzed their expression patterns during
      amphioxus embryogenesis. We found that these four Fz genes were maternally
      expressed and might be involved in early animal-vegetal axis establishment. The
      AmphiFz1/2/7 transcripts were detected in the central dorsal neural plate,
      mesoderm, the Hatschek's pit, and rim of the mouth, whereas those of AmphiFz4
      were detected in the mesoderm, pharyngeal endoderm, and entire gut region.
      AmphiFz5/8 was exclusively expressed in the anterior-most region, whereas
      AmphiFz9/10 was expressed in the neural plate, somites, and tail bud. The dynamic
      and diverse expression patterns of amphioxus Fz genes suggest that these genes
      are not only associated with early embryonic axis establishment but also are
      involved in the development of several organs in amphioxus. 

PMID- 24012524
TI  - The immunostimulatory effect of novel immunostimulator CH2b with a thiazolidin-4
      one ring on the functions of LPS-activated RAW 264.7 macrophages in vitro.
AB  - This study was designed to confirm the effect of the novel immunostimulators CH1b
      and CH2b with a thiazolidin-4-one ring on the function of macrophages. We used
      these two molecules to stimulate LPS-activated RAW 264.7 macrophages in vitro.
      After a series of essential assays, we found that CH1b and CH2b could
      significantly increase the production of nitric oxide (NO) by the LPS-activated
      RAW 264.7 macrophages, and also found that CH2b could more significantly increase
      the proliferation, phagocytic activity, and secretion of IL-6, IL-8 and TNF-alpha
      by LPS-activated RAW 264.7 cells more than CH1b. Furthermore, CH2b could increase
      the degradation of IkappaB-alpha and could promote the nuclear translocation of
      nuclear factor (NF)-kappaB p65 in LPS-activated RAW 264.7 cells. However, CH2b
      could also increase the phosphorylation of p38 mitogen-activated protein kinase
      (p38 MAPK). Taken together, we got that CH2b could further increase the LPS
      induced activation of NF-kappaB and p38 MAPK in RAW 264.7 macrophages to elevate
      the function of macrophages, including iNOS expression, NO production, cytokines
      secretion, and phagocytosis. 

PMID- 24012525
TI  - Obesity persistence and duration dependence: evidence from a cohort of US adults
      (1985-2010).
AB  - This study investigates dynamic patterns of obesity persistence and identifies
      the determinants of obesity-spell exits and re-entries. We utilize longitudinal
      data from the NLSY79 covering the period 1985-2010. Non-parametric techniques are
      applied to investigate the relationship between exit from obesity and spell
      duration. Multivariate discrete hazard models are also estimated, taking into
      account duration dependence and observed and time-invariant unobserved
      heterogeneity. In all cases, the probability of exiting obesity is inversely
      related to the duration of the obesity spell. Without controlling for unobserved
      heterogeneity, the probability of exit after one wave in obesity is 31.5 per
      cent; it is reduced to 3.8 per cent after seven or more waves. When time
      invariant unobserved heterogeneity is taken into account, the estimated
      probabilities are slightly larger and broadly similar (36.8 and 10.3,
      respectively), which suggests that the identified negative duration dependence is
      not primarily due to composition effects. The obtained results indicate that
      public health interventions targeting the newly obese may be particularly
      effective at reducing incidence of long durations of obesity. 

PMID- 24012523
TI  - Age-related alterations in regeneration of the urinary bladder after subtotal
      cystectomy.
AB  - Prior work documented that surgical removal of approximately 70% of the bladder
      (subtotal cystectomy) in 12-week-old female rats induced complete functional
      regeneration of the bladder within 8 weeks. To determine whether animal age
      affects bladder regeneration, female F344 rats aged 12 weeks (young) and 12
      months (old) underwent subtotal cystectomy, and then were evaluated from 1 to 26
      weeks after subtotal cystectomy. At 26 weeks after subtotal cystectomy, bladder
      capacity in young animals was indistinguishable from that in age-matched
      controls, but bladder capacity in old animals was only approximately 56% of that
      in age-matched controls. There was no detectable difference in residual volume
      among treatment groups, but the diminished regeneration in old animals was
      associated with a corresponding increase in the ratio of residual volume to
      micturition volume. The majority of old animals exhibited evidence of chronic
      kidney damage after subtotal cystectomy. Maximal contraction of bladder strips to
      electrical field stimulation, as well as activation with carbachol,
      phenylephrine, and KCl, were lower in old than in young animals at 26 weeks after
      subtotal cystectomy. Immunostaining with proliferating cell nuclear antigen and
      Von Willebrand factor revealed delayed and/or diminished proliferative and
      angiogenic responses, respectively, in old animals. These results confirm prior
      work and suggest that multiple mechanisms may contribute to an age-related
      decline in the regenerative capacity of the bladder. 

PMID- 24012526
TI  - Suppression of experimental abdominal aortic aneurysms in the mice by treatment
      with Ginkgo biloba extract (EGb 761).
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba extract (EGb 761) is widely used to
      treat cerebral disorders. Clinical trials have demonstrated therapeutic benefits
      of EGb 761 in various vascular diseases. Because the potential pathophysiological
      mechanisms appear similar to those involved in aneurysmal degeneration, we
      postulated that EGb 761 might affect the development and progression of
      experimental abdominal aortic aneurysm (AAA). This study was aimed to investigate
      whether EGb 761 influences the development of experimental AAAs, and to explore
      the underlying mechanisms. MATERIAL AND METHODS: C57/BL6 mice underwent abluminal
      application of CaCl2 to the abdominal aorta followed by gavages with either
      200mg/kg EGb 761 per day or vehicle. Six weeks after AAA induction, aortic tissue
      was excised for further examinations. RESULTS: EGb 761 treatment reduced the
      aneurysm size compared with vehicle-treated controls. EGb 761 had no effect on
      hemodynamics or macrophage infiltration in the aortic wall. However, nuclear
      factor kappaB protein levels were decreased in the aortas of EGb 761 treated
      animals. The increased ROS production, SOD and CAT activities, and mRNA
      expression of p47phox nicotinamide adenine dinucleotide phosphate oxidase were
      attenuated by EGb 761 treatment. Moreover, administration of EGb 761 preserved
      the destruction of the wavy morphology of the elastin during AAA formation.
      Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lowered in
      EGb 761 treated mice. CONCLUSIONS: These results suggest that treatment with EGb
      761 in mice prevented the development of CaCl2-induced AAA. The possible
      mechanisms include decreased oxidative damage and inflammation, preservation of
      aortic wall architecture, and altered MMPs activities.

PMID- 24012527
TI  - Natural product vindoline stimulates insulin secretion and efficiently
      ameliorates glucose homeostasis in diabetic murine models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Catharanthus roseus (L). Don (Catharanthus
      roseus) is a traditional anti-diabetic herb widely used in many countries, and
      the alkaloids of Catharanthus roseus are considered to possess hypoglycemic
      ability. AIM OF THE STUDY: To systematically investigate the potential anti
      diabetic effects and the underlying anti-diabetic mechanisms of vindoline, one of
      the alkaloids in Catharanthus roseus. MATERIALS AND METHODS: The regulation of
      vindoline against the glucose-stimulated insulin secretion (GSIS) was examined in
      insulinoma MIN6 cells and primary pancreatic islets. Insulin concentration was
      detected by Elisa assay. Diabetic models of db/db mice and type 2 diabetic rats
      induced by high-fat diet combining with streptozotocin (STZ/HFD-induced type 2
      diabetic rats) were used to evaluate the anti-diabetic effect of vindoline in
      vivo. Daily oral treatment with vindoline (20mg/kg) to diabetic mice/rats for 4
      weeks, body weight and blood glucose were determined every week, oral glucose
      tolerance test (OGTT) was performed after 4 weeks. RESULTS: Vindoline enhanced
      GSIS in both glucose- and dose-dependent manners (EC50 = 50 MUM). It was
      determined that vindoline acted as a Kv2.1 inhibitor able to reduce the voltage
      dependent outward potassium currents finally enhancing insulin secretion. It
      protected beta-cells from the cytokines-induced apoptosis following its
      inhibitory role in Kv2.1. Moreover, vindoline (20mg/kg) treatment significantly
      improved glucose homeostasis in db/db mice and STZ/HFD-induced type 2 diabetic
      rats, as reflected by its functions in increasing plasma insulin concentration,
      protecting the pancreatic beta-cells from damage, decreasing fasting blood
      glucose and glycated hemoglobin (HbA1c), improving OGTT and reducing plasma
      triglyceride (TG). CONCLUSION: Our findings suggested that vindoline might
      contribute to the anti-diabetic effects of Catharanthus roseus, and this natural
      product may find its more applications in the improvement of beta-cell
      dysfunction and further the potential treatment of type 2 diabetes.

PMID- 24012528
TI  - Calotropis gigantiea (L.) R. Br (Apocynaceae): a phytochemical and
      pharmacological review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Calotropis gigantiea (L.) R. Br (Apocynaceae)
      commonly called as "crown flower" or "giant milk weed" is a well-known weed to
      many cultures for treating various disorders related to central nervous system,
      skin diseases, digestive system, respiratory system, reproductive system etc.
      Indigenous groups made the plant as a part of their lives since they use the
      fruit fibre to make ropes, household items, for weaving clothes and flowers for
      garlands apart from usage for various indications. The study aims at far-reaching
      review on phytochemistry, pharmacological activities, ethnopharmacology,
      intellectual property transfer on pharmacological therapies, toxicity which aids
      to provide scientific evidence for the ethnobotanical claims and to identify gaps
      required to be conducted as a future research prerequisite. MATERIALS AND
      METHODS: A systematic literature search was performed using different databases
      such as Scopus, Science direct, PubMed and Sciverse with no timeline limit set
      during the search. All the available abstracts and full text articles were
      included in the systematic review. RESULTS: Most of the folkloric uses were
      validated by the scientific studies such as analgesic, anti-arthritic, anti
      asthmatic, anti-bacterial, anti-convulsant, anti-pyretic, central nervous system
      disorders, contraceptive, anti-ulcer and wound healing. In addition other studies
      such as anti-diabetic, anti-diarrhoeal, anti-helminthic, anti-histamine, anti
      inflammatory, anti-microbial, anti-oxidant, cardio-protective studies,
      cytotoxicity, hepatoprotectivity, fibrinolytic, mosquitocidal, nerve muscle
      activity, vasodilation and skeletal muscle activities were also reported for the
      plant. Isolated compounds such as calotropin, frugoside and 4'-O-beta-D
      glucopyranosyl frugoside were tested for the cytotoxicity efficacy against both
      human and rat cell lines out of which calotropin showed potent activity (IC50-15
      ng/ml). However there were no clinical trials reported on the plant which is one
      of the major lacunas. CONCLUSIONS: This review article explores the
      ethnopharmacological, pharmacological activities phytochemistry and intellectual
      rights of Cg which gives the evidence of a potent and commercial drug which up on
      further research leads to the most viable drug for variety of treatments. However
      there is further need for in-vivo studies and clinical trials on isolated
      phytoconstituents which will help to commercialise.

PMID- 24012529
TI  - Identification and analysis of absorbed components and their metabolites in rat
      plasma and tissues after oral administration of 'Ershiwuwei Shanhu' pill extracts
      by UPLC-DAD/Q-TOF-MS.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: 'Ershiwuwei Shanhu' pill (ESP), a classical and
      famous prescription of traditional Tibetan medicine, has a long history of
      empirical clinical use for the treatment of cerebrovascular and neurological
      diseases, but the absence of scientific evidence for its effect restricted its
      clinical application and further development. MATERIALS AND METHODS: The
      methodology of plasma pharmacochemistry was adopted to analyze the potentially
      bioactive components in ESP extracts. A method based on UPLC-DAD/Q-TOF-MS was
      established to identify herb components in ESP extracts and analyze the absorbed
      components of ESP and their metabolites in rat plasma, brain, heart, liver and
      kidney samples after oral administration of ESP extracts. RESULTS: A total of 61
      herb components were detected and identified in ESP extracts, while 35 absorbed
      components-including 19 prototype compounds and 16 metabolites-were discovered as
      potentially bioactive components in rat plasma and tissues by comparative
      analysis of the UV and MS chromatograms of ESP extracts, blank biosamples and
      dosed biosamples. CONCLUSIONS: The potentially bioactive components of ESP
      extracts identified from rat plasma and tissues provide useful information for
      further study of the pharmacology and mechanism of action of ESP.

PMID- 24012530
TI  - Proteomic approach for identifying gonad differential proteins in the oyster
      (Crassostrea angulata) following food-chain contamination with HgCl2.
AB  - Hg discharged into the environmental waters can generally be bioaccumulated,
      transformed and transmited by living organisms, thus resulting in the formation
      of Hg-toxicity food chains. The pathway and toxicology of food chain contaminated
      with environmental Hg are rarely revealed by proteomics. Here, we showed that
      differential proteomics had the potential to understand reproduction toxicity
      mechanism in marine molluscs through the Hg-contaminated food chain. Hg
      bioaccumulation was found in every link of the HgCl2-Chlorella vulgaris-oyster
      mice food chain. Morphological observations identified the lesions in both the
      oyster gonad and the mice ovary. Differential proteomics was used to study the
      mechanisms of Hg toxicity in the oyster gonad and to find some biomarkers of Hg
      contamination in food chain. Using 2-DE and MALDI-TOF/TOF MS, we identified 13
      differential protein spots, of which six were up-regulated, six were down
      regulated, while one was undecided. A portion of these differential proteins was
      further confirmed using real-time PCR and western blotting methods. Their major
      functions involved binding, protein translocation, catalysis, regulation of
      energy metabolism, reproductive functioning and structural molecular activity.
      Among these proteins, 14-3-3 protein, GTP binding protein, arginine kinase (AK)
      and 71kDa heat shock connate protein (HSCP 71) are considered to be suitable
      biomarkers of environmental Hg contamination. Furthermore, we established the
      gene correspondence, responding to Hg reproductive toxicity, between mouse and
      oyster, and then used real-time PCR to analyze mRNA differential expression of
      the corresponding genes in mice. The results indicated that the mechanism of Hg
      reproductive toxicity in mouse was similar to that in oyster. We suggest that the
      proteomics would be further developed in application research of food safety
      including toxicological mechanism. BIOLOGICAL SIGNIFICANCE: It is well known that
      mercury (Hg) is one of the best toxic metal elements in nature. The research
      reports as previously described indicated that multiple mercury compounds can
      directly contaminate the aquatic animals by flowing of water body and through the
      diffusion of air. The pollution sources of the mercury compounds in marine water
      were mainly found from the pathways such as steam power plant and mineral
      exploitation which are located on the inshore. Of note, after being released into
      environmental waters, mercury compounds undergo the processes of bioaccumulation,
      transformation and transmission in living organisms, thus resulting in the
      multiple forms of Hg found in Hg-toxicity food chains, and among them, methyl
      mercury (MeHg) showing the high toxic characteristics is the main form of Hg. The
      abundant reports indicated that the metal salts were easily found within the
      various organs of the animals, but it is difficult to judge the level of its
      perniciousness according to its content only in vivo. Here, the algae to have
      been contaminated by the mercury compounds have the ability for contaminating
      both the fish and shellfish as food pathway quickly. If these fish and shellfish
      edible as food will be taken by human, they will further affect the human health
      badly. However, studies about their perniciousness are rarely reported,
      especially in using proteomics. The oysters as normal food are largely consumed
      in Southern China, especially in Xiamen City. Similarly, a pathway question that
      the contaminated oysters can effect on the human health such as cancer is unclear
      or poorly understood. Here, we showed that an analytical technology such as
      differential proteomics has potential to understand toxicity mechanism induced by
      Hg-contamination through the food pathway. It is for reason that the oyster
      proteomics including relative analytical methods have been used to reveal the
      contaminant level and to determine its perniciousness using toxic algae as food.
      Here, we also indicated that the research here shows great significance for both
      analysis of food safety and toxicology of the metal compounds. In addition, a few
      biomarkers have shown their strong potential for monitoring the level of Hg
      pollution in sea in the manuscript and gene correspondence between mouse and
      oyster, the two contiguous links of the Hg-contaminated food chain, was further
      investigated to better illustrate our finding in the analysis of food chain
      proteomics. Moreover, similar research work is rarely reported compared to the
      current proteomic development, showing that a lot of novel results by proteomic
      methods in the manuscript have strong potential for developing the new area of
      food chain proteomics.

PMID- 24012531
TI  - Protective effect of flavonoid-rich extract from Rosa laevigata Michx on cerebral
      ischemia-reperfusion injury through suppression of apoptosis and inflammation.
AB  - The neuroprotective effect and mechanism of the flavonoid-rich extract (FRE) from
      Rosa laevigata Michx fruit on cerebral ischemia-reperfusion (I/R) injury were
      investigated. The contents of flavonoids, saponins and tannin were determined,
      and ten chemicals including chlorogenic acid, 4-hydroxy-3-methoxybenzoic acid,
      apigenin, luteolin, kaempferol, querce-tin, kaempferide-3-O-glucoside, quercetin
      3-rhamnoside, rutin and isorhamnetin-3-O-beta-rutinoside from the crude extract
      were separated. Oral administration of FRE obviously improved the survival rate
      and prevented I/R-induced disability and histological damage. Further works
      showed that the natural product had excellent antioxidant activity, significantly
      decreased DNA fragmentation, up-regulated the expression of Bcl-2, and down
      regulated the expressions of p53, Apaf1, Fas, FasL, Bax, Bid, cytochrome C and
      active Caspase-3, -9 and -8. Moreover, the FRE decreased the expressions of NF
      kappaB, iNOS, MMP-9, COX-2, TNF-alpha, IL-1beta, IL-4, IL-6, and down-regulated
      the levels of p-JNK, p-ERK and p-p38 in MAPK pathways. Therefore, the flavonoid
      rich extract from R. laevigata Michx fruit has the potential actions for
      treatment of ischemic stroke due to its anti-oxidant, anti-apoptosis and anti
      inflammatory properties. 

PMID- 24012532
TI  - Protective effects of N-acetylcysteine on experimentally undescended testis.
AB  - PURPOSE: We evaluated the efficacy of N-acetylcysteine for testicular damage
      induced by undescended testes in rats. MATERIALS AND METHODS: Flutamide was
      injected in the abdomen of pregnant rats daily from days 14 to 20 of gestation.
      Male offspring with cryptorchidism were randomly divided into 2 groups. Healthy
      male rats without undescended testes comprised the control group (group 1). Group
      2 (undescended testes without N-acetylcysteine) received no treatment. Group 3
      (undescended testes plus N-acetylcysteine) received intraperitoneal N
      acetylcysteine daily. At 70 days after experiment initiation the testes were
      removed for histopathological and biochemical analysis. RESULTS: Mean malonyl
      dialdehyde values were lowest in group 1 and highest in group 2. In group 3
      malonyl dialdehyde levels were significantly lower than in group 2 (p <0.001).
      Conversely, mean glutathione peroxidase was highest in group 1 and lowest in
      group 2. Glutathione peroxidase levels in group 3 were significantly higher than
      in group 2 (p <0.001). Histopathological differences between groups 1 and 3 in
      the modified Johnsen score were not significant (p = 0.041). However, the
      differences between these groups and group 2 were significant (p <0.001). The
      median apoptotic cell count did not differ between groups 1 and 3 but it was
      significantly higher in group 2 than in the other groups (p = 0.03 and <0.001,
      respectively). CONCLUSIONS: N-acetylcysteine may alleviate undescended testis
      induced damage to testes through its antioxidant effects. The underlying
      mechanism of these effects merits further investigation. Long-term studies are
      also needed as well as comparative animal and human studies.

PMID- 24012533
TI  - Expression and prognostic significance of a comprehensive epithelial-mesenchymal
      transition gene set in renal cell carcinoma.
AB  - PURPOSE: Epithelial-mesenchymal transition enhances tumor cell motility and has a
      critical role in invasion and metastasis in a number of carcinomas. A set of
      transcription factors acts as a master regulator of the epithelial-mesenchymal
      transition process. To our knowledge it is unknown whether epithelial-mesenchymal
      transition is important for clear cell renal cell carcinoma progression.
      Therefore, we comprehensively assessed mRNA levels of epithelial-mesenchymal
      transition associated genes in renal cell carcinoma as well as their prognostic
      relevance. MATERIALS AND METHODS: We determined the expression of a set of 46
      epithelial-mesenchymal transition related genes by oligonucleotide microarray and
      gene set enrichment analyses using RNA from 14 samples each of normal kidneys,
      and G1 and G3 primary renal cell carcinomas. Expression of select epithelial
      mesenchymal transition genes was validated by real-time polymerase chain reaction
      in normal kidneys, primary renal cell carcinomas and metastases in an independent
      cohort of 112 patients. Results were combined with followup data for survival
      analysis. RESULTS: The epithelial-mesenchymal transition gene set was
      preferentially expressed in primary renal cell carcinoma compared to normal
      tissue (false discovery rate 0.01). No difference was found between G1 and G3
      tumors. Quantitative reverse transcriptase-polymerase chain reaction revealed
      down-regulation of critical epithelial-mesenchymal transition genes such as CDH2
      and ZEB1 in metastases, suggesting epithelial-mesenchymal transition reversal
      during metastasis. Kaplan-Meier analysis demonstrated a better outcome in
      patients with low CXCR4, vimentin, fibronectin and TWIST1 mRNA levels.
      Multivariate analyses revealed that CXCR4 and VIM up-regulation represents an
      independent prognostic marker for poor cancer specific survival in patients with
      renal cell carcinoma. CONCLUSIONS: Taken together, our data provide strong
      evidence that epithelial-mesenchymal transition occurs in renal cell carcinoma.
      Thus, interference with epithelial-mesenchymal transition in renal cell carcinoma
      might represent a future therapeutic option.

PMID- 24012535
TI  - Effect of repeated prostate biopsies on erectile function in men on active
      surveillance for prostate cancer.
AB  - PURPOSE: Active surveillance is becoming an increasingly common management
      strategy for low grade prostate cancer and involves repeat prostate biopsies over
      time. It has been hypothesized that serial biopsies can lead to reduced erectile
      function in patients on active surveillance and we explored this hypothesis in a
      longitudinally followed cohort. MATERIALS AND METHODS: We identified 342 men on
      active surveillance whose first biopsy occurred between 2000 and 2009. We
      investigated erectile function using patient reported outcomes, namely the 6
      erectile function questions from the IIEF-6 (International Index of Erectile
      Function). We estimated the change in erectile function with time using locally
      weighted scatterplot smoothing. RESULTS: The median (IQR) patient age in this
      cohort was 64 years (58-68). Median followup on active surveillance was 3.5 years
      (2.3-5.0) and the median number of biopsies was 5 (3-6). During the first 4 years
      on active surveillance erectile function decreased 1.0 point per year (95% CI
      0.2, 1.7) on the IIEF-6 (scale 1 to 30). When stratified by comorbidities or
      number of biopsies we see an almost identical decrease in erectile function with
      time. The use of phosphodiesterase-5 inhibitors increased from 5% to 27% from
      baseline to year 5 on active surveillance. CONCLUSIONS: In this longitudinally
      followed active surveillance cohort we observed a small decrease in erectile
      function and an increase in the use of phosphodiesterase-5 inhibitors with time.
      While we cannot separate out the effect of multiple biopsies from that of the
      natural aging process on erectile function in this observational study, our data
      suggest that active surveillance related biopsies do not have a large impact on
      erectile function.

PMID- 24012536
TI  - Potential schistosomiasis foci in China: a prospective study for schistosomiasis
      surveillance and response.
AB  - Schistosomiasis japonica was endemic in 12 provinces (including municipalities
      and autonomous regions) in the People's Republic of China (PR China). Despite the
      tremendous decrease of schistosomiasis incidence after almost 60 years of
      control, the distribution of snail-breeding sites has not been reduced
      significantly. In order to verify current transmission risks and identify the
      potential establishment of new foci of schistosomiasis driven by environmental
      changes, we conducted surveillance in selected risk areas of three provinces:
      Jiangsu, Anhui and Shandong from 2008 to 2010 in addition to routine snail
      surveillance. We investigated populations and possible reservoirs in sentinel
      sites and report that the total number of new acute cases did not diminish
      further in spite of ongoing control activities. In Anhui Province the local count
      compared to the national count was 43% (19/44) in 2008, 33% (25/75) in 2009 and
      40% (17/42) in 2010. In all, 31.58 km(2) areas of snail breeding sites were newly
      detected nationwide through the year 2008-2010, of which the proportion of Anhui
      was 42% (5.03/11.98) in 2008, 95% (8.39/8.79) in 2009 and 79% (8.52/10.81) in
      2010. Sentinel surveillance showed eight, nine and five confirmed cases of acute
      schistosomiasis in mobile populations (fishermen, migrant workers) in 2008, 2009
      and 2010, respectively. All these cases were detected in Chaohu County, which
      must therefore be deemed an area at risk. We conclude that continuous
      surveillance with an emphasis on snails must be enhanced in potential risk areas
      in PR China.

PMID- 24012537
TI  - Sulfide oxidation, nitrate respiration, carbon acquisition, and electron
      transport pathways suggested by the draft genome of a single orange Guaymas Basin
      Beggiatoa (Cand. Maribeggiatoa) sp. filament.
AB  - A near-complete draft genome has been obtained for a single vacuolated orange
      Beggiatoa (Cand. Maribeggiatoa) filament from a Guaymas Basin seafloor microbial
      mat, the third relatively complete sequence for the Beggiatoaceae. Possible
      pathways for sulfide oxidation; nitrate respiration; inorganic carbon fixation by
      both Type II RuBisCO and the reductive tricarboxylic acid cycle; acetate and
      possibly formate uptake; and energy-generating electron transport via both
      oxidative phosphorylation and the Rnf complex are discussed here. A role in
      nitrite reduction is suggested for an abundant orange cytochrome produced by the
      Guaymas strain; this has a possible homolog in Beggiatoa (Cand. Isobeggiatoa) sp.
      PS, isolated from marine harbor sediment, but not Beggiatoa alba B18LD, isolated
      from a freshwater rice field ditch. Inferred phylogenies for the Calvin-Benson
      Bassham (CBB) cycle and the reductive (rTCA) and oxidative (TCA) tricarboxylic
      acid cycles suggest that genes encoding succinate dehydrogenase and enzymes for
      carboxylation and/or decarboxylation steps (including RuBisCO) may have been
      introduced to (or exported from) one or more of the three genomes by horizontal
      transfer, sometimes by different routes. Sequences from the two marine strains
      are generally more similar to each other than to sequences from the freshwater
      strain, except in the case of RuBisCO: only the Guaymas strain encodes a Type II
      enzyme, which (where studied) discriminates less against oxygen than do Type I
      RuBisCOs. Genes subject to horizontal transfer may represent key steps for
      adaptation to factors such as oxygen and carbon dioxide concentration, organic
      carbon availability, and environmental variability. 

PMID- 24012538
TI  - Dynamics of the late Na(+) current during cardiac action potential and its
      contribution to afterdepolarizations.
AB  - The objective of this work is to examine the contribution of late Na(+) current
      (INa,L) to the cardiac action potential (AP) and arrhythmogenic activities. In
      spite of the rapidly growing interest toward this current, there is no
      publication available on experimental recording of the dynamic INa,L current as
      it flows during AP with Ca(2+) cycling. Also unknown is how the current profile
      changes when the Ca(2+)-calmodulin dependent protein kinase II (CaMKII) signaling
      is altered, and how the current contributes to the development of arrhythmias. In
      this study we use an innovative AP-clamp Sequential Dissection technique to
      directly record the INa,L current during the AP with Ca(2+) cycling in the guinea
      pig ventricular myocytes. First, we found that the magnitude of INa,L measured
      under AP-clamp is substantially larger than earlier studies indicated. CaMKII
      inhibition using KN-93 significantly reduced the current. Second, we recorded
      INa,L together with IKs, IKr, and IK1 in the same cell to understand how these
      currents counterbalance to shape the AP morphology. We found that the amplitude
      and the total charge carried by INa,L exceed that of IKs. Third, facilitation of
      INa,L by Anemone toxin II prolonged APD and induced Ca(2+) oscillations that led
      to early and delayed afterdepolarizations and triggered APs; these arrhythmogenic
      activities were eliminated by buffering Ca(2+) with BAPTA. In conclusion, INa,L
      contributes a significantly large inward current that prolongs APD and unbalances
      the Ca(2+) homeostasis to cause arrhythmogenic APs. 

PMID- 24012539
TI  - Dopaminergic D2 receptor is a key player in the substantia nigra pars compacta
      neuronal activation mediated by REM sleep deprivation.
AB  - Currently, several studies addresses the novel link between sleep and
      dopaminergic neurotransmission, focusing most closely on the mechanisms by which
      Parkinson's disease (PD) and sleep may be intertwined. Therefore, variations in
      the activity of afferents during the sleep cycles, either at the level of DA cell
      bodies in the ventral tegmental area (VTA) and/or substantia nigra pars compacta
      (SNpc) or at the level of dopamine (DA) terminals in limbic areas may impact
      functions such as memory. Accordingly, we performed striatal and hippocampal
      neurochemical quantifications of DA, serotonin (5-HT) and metabolites of rats
      intraperitoneally treated with haloperidol (1.5 mg/kg) or piribedil (8 mg/kg) and
      submitted to REM sleep deprivation (REMSD) and sleep rebound (REB). Also, we
      evaluated the effects of REMSD on motor and cognitive parameters and SNpc c-Fos
      neuronal immunoreactivity. The results indicated that DA release was strongly
      enhanced by piribedil in the REMSD group. In opposite, haloperidol prevented that
      alteration. A c-Fos activation characteristic of REMSD was affected in a synergic
      manner by piribedil, indicating a strong positive correlation between striatal DA
      levels and nigral c-Fos activation. Hence, we suggest that memory process is
      severely impacted by both D2 blockade and REMSD and was even more by its
      combination. Conversely, the activation of D2 receptor counteracted such memory
      impairment. Therefore, the present evidence reinforce that the D2 receptor is a
      key player in the SNpc neuronal activation mediated by REMSD, as a consequence
      these changes may have direct impact for cognitive and sleep abnormalities found
      in patients with PD. This article is part of the Special Issue entitled 'The
      Synaptic Basis of Neurodegenerative Disorders'. 

PMID- 24012541
TI  - Exploration and prediction of interactions between methanotrophs and
      heterotrophs.
AB  - Methanotrophs can form the basis of a methane-driven food web on which
      heterotrophic microorganisms can feed. In return, these heterotrophs can
      stimulate growth of methanotrophs in co-culture by providing growth additives.
      However, only a few specific interactions are currently known. We incubated nine
      methanotrophs with 25 heterotrophic strains in a pairwise miniaturized co
      cultivation setup. Through principal component analysis and k-means clustering,
      methanotrophs and heterotrophs could be grouped according to their interaction
      behaviour, suggesting strain-dependent methanotroph-heterotroph complementarity.
      Co-cultivation significantly enhanced the growth parameters of three
      methanotrophs. This was most pronounced for Methylomonas sp. M5, with a threefold
      increase in maximum density and a fourfold increase in maximum increase in
      density in co-culture with Cupriavidus taiwanensis LMG 19424. In contrast, co
      cultivation with Methylobacterium radiotolerans LMG 2269 and Pseudomonas
      aeruginosa LMG 12228 inhibited growth of most methanotrophs. Functional genomic
      analysis suggested the importance of vitamin metabolism for co-cultivation
      success. The generated data set was then successfully exploited as a proof-of
      principle for predictive modelling of co-culture responses based on other
      interactions of the same heterotrophs and methanotrophs, yielding values of the
      area under the receiver operating characteristic curve of 0.73 upon 50% missing
      values for the maximum increase in density parameter. As such, these modelling
      based tools were shown to hold great promise in reducing the amount of data that
      needs to be generated when conducting large co-cultivation studies.

PMID- 24012542
TI  - Characterization and complete genome sequence of the Shigella bacteriophage pSf
      1.
AB  - Shigellosis is a global health problem, and Shigella flexneri is the major cause
      of this disease. In this study, we isolated a virulent Siphoviridae bacteriophage
      (phage), pSf-1, that infects S. flexneri. This phage was isolated from the Han
      River in Korea and was found to infect S. flexneri, Shigella boydii, and Shigella
      sonnei. One-step growth analysis revealed that this phage has a short latent
      period (10 min) and a large burst size (86.86 PFU/cell), indicating that pSf-1
      has good host infectivity and effective lytic activity. The double-stranded DNA
      genome of pSf-1 is composed of 51,821 bp with a G + C content of 44.02%. The
      genome encodes 94 putative ORFs, 71 putative promoters, and 60 transcriptional
      terminator regions. Genome sequence analysis of pSf-1 and comparative analysis
      with the homologous Shigella phage Shfl1 revealed that there is a high degree of
      similarity between pSf-1 and Shfl1 in 54 of the 94 ORFs of pSf-1. The results of
      this investigation indicate that pSf-1 is a novel Shigella phage and that this
      phage might have potential uses against shigellosis.

PMID- 24012540
TI  - Activity and bacterial diversity of snow around Russian Antarctic stations.
AB  - The diversity and temporal dynamics of bacterial communities in pristine snow
      around two Russian Antarctic stations was investigated. Taxonomic analysis of
      rDNA libraries revealed that snow communities were dominated by bacteria from a
      small number of operational taxonomic units (OTUs) that underwent dramatic swings
      in abundance between the 54th (2008-2009) and 55th (2009-2010) Russian Antarctic
      expeditions. Moreover, analysis of the 55th expedition samples indicated that
      there was very little, if any, correspondence in abundance of clones belonging to
      the same OTU present in rDNA and rRNA libraries. The latter result suggests that
      most rDNA clones originate from bacteria that are not alive and/or active and may
      have been deposited on the snow surface from the atmosphere. In contrast, clones
      most abundant in rRNA libraries (mostly belonging to Variovorax,
      Janthinobacterium, Pseudomonas, and Sphingomonas genera) may be considered as
      endogenous Antarctic snow inhabitants. 

PMID- 24012544
TI  - PKH(high) cells within clonal human nephrospheres provide a purified adult renal
      stem cell population.
AB  - The existence and identification of adult renal stem cells is a controversial
      issue. In this study, renal stem cells were identified from cultures of clonal
      human nephrospheres. The cultured nephrospheres exhibited the activation of stem
      cell pathways and contained cells at different levels of maturation. In each
      nephrosphere the presence of 1.12-1.25 cells mirroring stem cell properties was
      calculated. The nephrosphere cells were able to generate three-dimensional
      tubular structures in 3D cultures and in vivo. In clonal human nephrospheres a
      PKH(high) phenotype was isolated using PKH26 epifluorescence, which can identify
      quiescent cells within the nephrospheres. The PKH(high) cells, capable of self
      renewal and of generating a differentiated epithelial, endothelial and podocytic
      progeny, can also survive in vivo maintaining the undifferentiated status. The
      PKH(high) status, together with a CD133(+)/CD24(-) phenotype, identified a
      homogeneous cell population displaying in vitro self-renewal and multipotency
      capacity. The resident adult renal stem cell population isolated from
      nephrospheres can be used for the study of mechanisms that regulate self-renewal
      and differentiation in adult renal tissue as well as in renal pathological
      conditions. 

PMID- 24012543
TI  - Dietary suppression of the mammary CD29(hi)CD24(+) epithelial subpopulation and
      its cytokine/chemokine transcriptional signatures modifies mammary tumor risk in
      MMTV-Wnt1 transgenic mice.
AB  - Diet is highly linked to breast cancer risk, yet little is known about its
      influence on mammary epithelial populations with distinct regenerative and hence,
      tumorigenic potential. To investigate this, we evaluated the relative frequency
      of lineage-negative CD29(hi)CD24(+), CD29(lo)CD24(+) and CD29(hi)Thy1(+)CD24(+)
      epithelial subpopulations in pre-neoplastic mammary tissue of adult virgin MMTV
      Wnt1-transgenic mice fed either control (Casein) or soy-based diets. We found
      that mammary epithelial cells exposed to soy diet exhibited a lower percentage of
      CD29(hi)CD24(+)Lin(-) population, decreased ability to form mammospheres in
      culture, lower mammary outgrowth potential when transplanted into cleared fat
      pads, and reduced appearance of tumor-initiating CD29(hi)Thy1(+)CD24(+) cells,
      than in those of control diet-fed mice. Diet had no comparable influence on the
      percentage of the CD29(lo)CD24(+)Lin(-) population. Global gene expression
      profiling of the CD29(hi)CD24(+)subpopulation revealed markedly altered
      expression of genes important to inflammation, cytokine and chemokine signaling,
      and proliferation. Soy-fed relative to casein-fed mice showed lower mammary tumor
      incidence, shorter tumor latency, and reduced systemic levels of estradiol 17
      beta, progesterone and interleukin-6. Our results provide evidence for the
      functional impact of diet on specific epithelial subpopulations that may relate
      to breast cancer risk and suggest that diet-regulated cues can be further
      explored for breast cancer risk assessment and prevention. 

PMID- 24012545
TI  - Competitive mechanisms in sentence processing: common and distinct production and
      reading comprehension networks linked to the prefrontal cortex.
AB  - Despite much interest in language production and comprehension mechanisms, little
      is known about the relationship between the two. Previous research suggests that
      linguistic knowledge is shared across these tasks and that the left inferior
      frontal gyrus (LIFG) may be commonly recruited. However, it remains unclear the
      extent to which production and comprehension share competition mechanisms. Here
      we investigate this issue and specifically examine competition in determining the
      event roles in a sentence (agent or affected participant). We used both
      behavioral and fMRI methods and compared the reading and production of high- and
      low-competition sentences, specifically targeting LIFG. We found that activity in
      pars opercularis (PO), independently identified by a competition-driven
      localizer, was modulated by competition in both tasks. Psychophysiological
      interaction analyses seeded in PO revealed task-specific networks: In
      comprehension, PO only interacted with the posterior temporal lobe, whereas in
      production, it interacted with a large network including hippocampal, posterior
      temporal, medial frontal and subcortical structures. Production and comprehension
      therefore recruit partially distinct functional networks but share competitive
      processes within fronto-temporal regions. We argue that these common regions
      store long-term linguistic associations and compute their higher-order
      contingencies, but competition in production ignites a larger neural network
      implementing planning, as required by task demands. 

PMID- 24012547
TI  - Diagnostic role of glypican 3 and CD34 for differentiating hepatocellular
      carcinoma from nonmalignant hepatocellular lesions.
AB  - Well-differentiated hepatocellular carcinoma (HCC) may be difficult to
      distinguish from a benign lesion. Glypican 3 (GPC-3) is an oncofetal protein,
      which has been demonstrated to be up-regulated in HCC. The aim of this study is
      to evaluate the diagnostic role of combined GPC-3 and CD34 immunoassaying in the
      distinction between HCC and benign hepatic mimickers. This study was performed on
      100 cases of formalin-fixed, paraffin-embedded cases of hepatic focal lesions
      obtained from the files of pathology laboratory of our university from 2009 to
      2012. The following groups were studied: group A (n = 60) (hepatocellular
      malignant lesions) and group B (n = 40) (Hepatocellular nonmalignant lesions).
      All cases were stained with GPC-3 and CD34. Sensitivity, specificity, and
      positive and negative predictive values were calculated for both antibodies.
      Glypican 3 and complete CD34 staining pattern expression in group A was
      significantly higher than in group B. The results of costaining showed that, in
      HCCs, almost all the GPC-3-positive cases had a complete CD34 staining pattern,
      whereas in the 40 hepatocellular nonmalignant lesions, none stained up with the 2
      markers. Therefore, although the sensitivity declined (82%), the specificity and
      positive predictive value (PPV) of costaining reached 100% and were greater than
      that observed for single staining with GPC-3 (specificity, 92.5%; PPV, 94.3%) or
      CD34 (specificity, 97.5%; PPV, 98.3%). Our data demonstrate that GPC-3 and CD34
      costaining has better diagnostic value for differentiating HCC from nonmalignant
      hepatocellular lesions than does single staining.

PMID- 24012546
TI  - The shared neural basis of empathy and facial imitation accuracy.
AB  - Empathy involves experiencing emotion vicariously, and understanding the reasons
      for those emotions. It may be served partly by a motor simulation function, and
      therefore share a neural basis with imitation (as opposed to mimicry), as both
      involve sensorimotor representations of intentions based on perceptions of
      others' actions. We recently showed a correlation between imitation accuracy and
      Empathy Quotient (EQ) using a facial imitation task and hypothesised that this
      relationship would be mediated by the human mirror neuron system. During
      functional Magnetic Resonance Imaging (fMRI), 20 adults observed novel 'blends'
      of facial emotional expressions. According to instruction, they either imitated
      (i.e. matched) the expressions or executed alternative, pre-prescribed mismatched
      actions as control. Outside the scanner we replicated the association between
      imitation accuracy and EQ. During fMRI, activity was greater during mismatch
      compared to imitation, particularly in the bilateral insula. Activity during
      imitation correlated with EQ in somatosensory cortex, intraparietal sulcus and
      premotor cortex. Imitation accuracy correlated with activity in insula and areas
      serving motor control. Overlapping voxels for the accuracy and EQ correlations
      occurred in premotor cortex. We suggest that both empathy and facial imitation
      rely on formation of action plans (or a simulation of others' intentions) in the
      premotor cortex, in connection with representations of emotional expressions
      based in the somatosensory cortex. In addition, the insula may play a key role in
      the social regulation of facial expression. 

PMID- 24012548
TI  - GABAA receptor plasticity in Jurkat T cells.
AB  - GABAA receptors (GABAAR) mediate inhibitory neurotransmission in the human brain.
      Neurons modify subunit expression, cellular distribution and function of GABAAR
      in response to different stimuli, a process named plasticity. Human lymphocytes
      have a functional neuronal-like GABAergic system with GABAAR acting as inhibitors
      of proliferation. We here explore if receptor plasticity occurs in lymphocytes.
      To this end, we analyzed human T lymphocyte Jurkat cells exposed to different
      physiological stimuli shown to mediate plasticity in neurons: GABA, progesterone
      and insulin. The exposure to 100 MUM GABA differently affected the expression of
      GABAAR subunits measured at both the mRNA and protein level, showing an increase
      of alpha1, beta3, and gamma2 subunits but no changes in delta subunit. Exposure
      of Jurkat cells to different stimuli produced different changes in subunit
      expression: 0.1 MUM progesterone decreased delta and 0.5 MUM insulin increased
      beta3 subunits. To identify the mechanisms underlying plasticity, we evaluated
      the Akt pathway, which is involved in the phosphorylation of beta subunits and
      receptor translocation to the membrane. A significant increase of phosphorylated
      Akt and on the expression of beta3 subunit in membrane occurred in cells exposed
      15 h to GABA. To determine if plastic changes are translated into functional
      changes, we performed whole cell recordings. After 15 h GABA-exposure, a
      significantly higher percentage of cells responded to GABA application when
      compared to 0 and 40 h exposure, thus indicating that the detected plastic
      changes may have a role in GABA-modulated lymphocyte function. Our results reveal
      that lymphocyte GABAAR are modified by different stimuli similarly and by similar
      mechanisms to those in neurons. This property is of significance for the
      development of future therapies involving pharmacological modulation of the
      immune response.

PMID- 24012549
TI  - The effect of small molecules on nuclear-encoded translation diseases.
AB  - The five complexes of the mitochondrial respiratory chain (MRC) supply most
      organs and tissues with ATP produced by oxidative phosphorylation (OXPHOS).
      Inherited mitochondrial diseases affecting OXPHOS dysfunction are heterogeneous;
      symptoms may present at any age and may affect a wide range of tissues, with many
      diseases giving rise to devastating multisystemic disorders resulting in neonatal
      death. Combined respiratory chain deficiency with normal complex II accounts for
      a third of all respiratory deficiencies; mutations in nuclear-encoded components
      of the mitochondrial translation machinery account for many cases. Although
      mutations have been identified in over 20 such genes and our understanding of the
      mitochondrial translation apparatus is increasing, to date no definitive cure for
      these disorders exists. We evaluated the effect of seven small molecules with
      reported therapeutic potential in fibroblasts of four patients with combined
      respiratory complex disorders, each harboring a known mutation in a different
      nuclear-encoded component of the mitochondrial translation machinery: EFTs, GFM1,
      MRPS22 and TRMU. Six mitochondrial parameters were screened as follows; growth in
      glucose-free medium, reactive oxygen species (ROS) production, ATP content,
      mitochondrial content, mitochondrial membrane potential and complex IV activity.
      It was clearly evident that each patient displayed an individual response and
      there was no universally beneficial compound. AICAR increased complex IV activity
      in GFM1 cells and increased ATP content in MRPS22 fibroblasts but was detrimental
      to TRMU, who benefitted from bezafibrate. Two antioxidants, ascorbate and N
      acetylcysteine (NAC), significantly improved cell growth, ATP content and
      mitochondrial membrane potential and decreased levels of intracellular reactive
      oxygen species (ROS) in EFTs fibroblasts. This study presents an expanded
      repertoire of assays that can be performed using the microtiter screening system
      with a small number of patients' fibroblasts and highlights some therapeutic
      options while providing additional evidence for the importance of personalized
      medicine in mitochondrial disorders. 

PMID- 24012550
TI  - Metabolic functions of peroxisomes in health and disease.
AB  - Peroxisomes are subcellular organelles which are present in virtually every
      eukaryotic cell and catalyze a large number of metabolic functions. The
      importance of peroxisomes for humans is stressed by the existence of a large
      group of genetic diseases in which either the biogenesis of peroxisomes is
      impaired or one of its metabolic functions. Thanks to the work on Zellweger
      syndrome which is the prototype of the group of peroxisomal disorders, much has
      been learned about the metabolism and biogenesis of peroxisomes in humans. These
      metabolic functions include: (1.) fatty acid beta-oxidation; (2.)
      etherphospholipid biosynthesis; (3.) fatty acid alpha-oxidation, and (4.)
      glyoxylate detoxification. Since peroxisomes lack a citric acid cycle and a
      respiratory chain, peroxisomes are relatively helpless organelles which rely
      heavily on their cross-talk with other subcellular organelles in order to
      metabolize the end products of metabolism as generated in peroxisomes. The
      metabolic functions of peroxisomes in humans will be briefly described in this
      review with emphasis on the cross-talk with other subcellular organelles as well
      as the peroxisomal disorders in which one or more peroxisomal functions are
      impaired. 

PMID- 24012551
TI  - NMR structure of 2'-O-(2-methoxyethyl) modified and C5-methylated RNA dodecamer
      duplex.
AB  - The solution-state structure of 2'-O-(2-methoxyethly) substituted dodecamer
      r(*CG*CGAA*U*U*CG*C)d(G), 2'-MOE RNA, with all cytosines and uracils methylated
      at the C5-position has been determined by NMR spectroscopy. The chemical
      modifications were used to improve the oligonucleotide's drug-like properties.
      The 2'-MOE group drives pseudorotational equilibrium of the ribofuranose moiety
      to the N-type conformation and supposedly results in structural preorganization
      leading to high affinity of a modified oligonucleotide towards its complementary
      biological target, improved pharmacokinetic and toxicological properties. The
      high melting temperature of the antiparallel duplex structure adopted by 2'-MOE
      RNA was explained through the formation of a stable A-form RNA consistent with
      effective base-pairing and stacking interactions. The comparison of the solution
      state structure with the crystal structure of a non-methylated analogue shows an
      increase in the stacking at the base pair steps for the C5-methylated 2'-MOE RNA
      duplex. The MOE substituents adopt a well-defined structure in the minor groove
      with the predominant gauche conformations around the ethylene bond. 

PMID- 24012552
TI  - The occipital transtentorial approach for cerebellar and midbrain arteriovenous
      malformation.

PMID- 24012553
TI  - The human factor and safety attitudes in neurosurgical operating rooms.

PMID- 24012554
TI  - The Cushing-Dandy conflict-two powerful personalities that were best not to
      collide!

PMID- 24012555
TI  - Parasellar meningiomas in pregnancy.

PMID- 24012556
TI  - Is neurosurgery safe?

PMID- 24012557
TI  - New lesions on diffusion-weighted imaging after carotid endarterectomy: a measure
      of surgical quality.

PMID- 24012558
TI  - Giant arteriovenous malformation of the colon mimicking lipoma.

PMID- 24012560
TI  - A combination of site-directed mutagenesis and chemical modification to improve
      diastereopreference of Pseudomonas alcaligenes lipase.
AB  - A combination of site-directed mutagenesis and chemical modification was employed
      to alter protein structure with the objective of improving diastereopreference
      over that achieved by simple site-directed mutagenesis. Conformational analysis
      using molecular dynamic (MD) simulation of Pseudomonas alcaligenes lipase (PAL)
      indicated that stronger steric exclusion and structural rigidity facilitated
      diastereopreference. A cysteine (Cys) residue was introduced using site-directed
      mutagenesis to construct variant A272C. The modifier 5,5'-dithiobis-(2
      nitrobenzoic acid) (DTNB) was then reacted with the introduced Cys residue to
      provide stronger steric exclusion and structural rigidity. The modification was
      verified by matrix-assisted laser desorption/ionization time-of-flight (MALDI
      TOF) mass spectrometry. Diastereopreference was improved significantly. The
      diastereomeric excess (dep) of l-menthol increased from 35% with wild type PAL to
      90% with A272C-DTNB modified PAL when the conversion ratio of l-menthyl
      propionate was nearly 100%. Conformation and kinetic parameter analysis showed
      that A272C-DTNB modified PAL exhibited stronger steric exclusion and increased
      structural rigidity around the modification site that inhibited the hydrolysis of
      non-targeted substrates. The combination of site-directed mutagenesis and
      chemical modification could be an effective method to alter protein properties
      and enhance diastereopreference through the combined effect of steric exclusion
      and structural rigidity. 

PMID- 24012559
TI  - The impact of opiate pain medications and psychoactive drugs on the quality of
      colon preparation in outpatient colonoscopy.
AB  - BACKGROUND: Suboptimal colon preparation is a significant barrier to quality
      colonoscopy. The impact of pharmacologic agents associated with gastrointestinal
      dysmotility on quality of colon preparation has not been well characterized.
      AIMS: Evaluate impact of opiate pain medication and psychoactive medications on
      colon preparation quality in outpatients undergoing colonoscopy. METHODS:
      Outpatients undergoing colonoscopy at a single medical centre during a 6-month
      period were retrospectively identified. Demographics, clinical characteristics
      and pharmacy records were extracted from electronic medical records. Colon
      preparation adequacy was evaluated using a validated composite colon preparation
      score. RESULTS: 2600 patients (57.3 +/- 12.9 years, 57% female) met the inclusion
      and exclusion criteria. 223 (8.6%) patients were regularly using opioids, 92
      antipsychotics, 83 tricyclic antidepressants and 421 non-tricyclic
      antidepressants. Opioid use was associated with inadequate colon preparation both
      with low dose (OR = 1.4, 95%CI 1.0-2.1, p = 0.05) and high dose opioid users (OR
      = 1.7, 95%CI 1.1-2.9, p = 0.039) in a dose dependent manner. Other significant
      predictors of inadequate colon preparation included use of tricyclics (OR = 1.9,
      95%CI 1.1-3.0, p = 0.012), non-tricyclic antidepressants (OR = 1.5, 95%CI 1.1
      2.0, p = 0.013), and antipsychotic medications (OR = 2.2, 95%CI 1.4-3.4, p =
      0.001). CONCLUSIONS: Opiate pain medication use independently predicts inadequate
      quality colon preparation in a dose dependent fashion; furthermore psychoactive
      medications have even more prominent effects and further potentiates the negative
      impact of opiates with concurrent use.

PMID- 24012561
TI  - A computational analysis of non-genomic plasma membrane progestin binding
      proteins: signaling through ion channel-linked cell surface receptors.
AB  - A number of plasma membrane progestin receptors linked to non-genomic events have
      been identified. These include: (1) alpha1-subunit of the Na(+)/K(+)-ATPase
      (ATP1A1), (2) progestin binding PAQR proteins, (3) membrane progestin receptor
      alpha (mPRalpha), (4) progesterone receptor MAPR proteins and (5) the association
      of nuclear receptor (PRB) with the plasma membrane. This study compares: the pore
      lining regions (ion channels), transmembrane (TM) helices, caveolin binding (CB)
      motifs and leucine-rich repeats (LRRs) of putative progesterone receptors. ATP1A1
      contains 10 TM helices (TM-2, 4, 5, 6 and 8 are pores) and 4 CB motifs; whereas
      PAQR5, PAQR6, PAQR7, PAQRB8 and fish mPRalpha each contain 8 TM helices (TM-3 is
      a pore) and 2-4 CB motifs. MAPR proteins contain a single TM helix but lack pore
      lining regions and CB motifs. PRB contains one or more TM helices in the steroid
      binding region, one of which is a pore. ATP1A1, PAQR5/7/8, mPRalpha, and MAPR-1
      contain highly conserved leucine-rich repeats (LRR, common to plant membrane
      proteins) that are ligand binding sites for ouabain-like steroids associated with
      LRR kinases. LRR domains are within or overlap TM helices predicted to be ion
      channels (pore-lining regions), with the variable LRR sequence either at the C
      terminus (PAQR and MAPR-1) or within an external loop (ATP1A1). Since ouabain
      like steroids are produced by animal cells, our findings suggest that ATP1A1,
      PAQR5/7/8 and mPRalpha represent ion channel-linked receptors that respond
      physiologically to ouabain-like steroids (not progestin) similar to those known
      to regulate developmental and defense-related processes in plants. 

PMID- 24012562
TI  - Biosynthesis of polar steroids from the Far Eastern starfish Patiria (=Asterina)
      pectinifera. Cholesterol and cholesterol sulfate are converted into
      polyhydroxylated sterols and monoglycoside asterosaponin P1 in feeding
      experiments.
AB  - For the first time, it is experimentally established that the dietary cholesterol
      and cholesterol sulfate are biosynthetic precursors of polyhydroxysteroids and
      related low molecular weight glycosides in starfishes. These deuterium labeled
      precursors were converted into partly deuterated 5alpha-cholestane
      3beta,6alpha,7alpha,8,15alpha,16beta,26-heptaol, 5alpha-cholestane
      3beta,4beta,6alpha,7alpha,8,15beta,16beta,26-octaol, and steroid monoside
      asterosaponin P1 in result of feeding experiments on the Far Eastern starfish
      Patiria (=Asterina) pectinifera. The incorporations of deuterium were established
      by MS and NMR spectroscopy. Scheme of the first stages of biosynthesis of polar
      steroids in these animals was suggested on the basis of inclusion of three from
      six deuterium atoms and determination of their positions in biosynthetic
      products, when [2,2,3,4,4,6-(2)H6]cholesterol 3-sulfate was used as precursor. It
      was also shown that labeled cholesterol is transformed into Delta(7)-cholesterol
      (lathosterol) in digestive organs and gonads of the starfish. 

PMID- 24012563
TI  - Executive functions, physical fitness and mobility in well-functioning older
      adults.
AB  - The objective of this study was to examine the relationships between executive
      functions, physical fitness and mobility in well-functioning older adults. Forty
      eight well functioning older adults (70.5+/-5.3years old; 20 men, 28 women) were
      included in this study. Two median splits were conducted based on each
      individual's performance for the 10MWT and TUG. Comparisons between groups of
      slower and faster individuals were made with regard to executive functions and
      physical fitness parameters. A correlational approach was used to assess the
      association between variables. Between groups comparisons revealed that faster
      individuals in mobility tests demonstrate better performances in measures of
      cognitive flexibility (0.68<g<0.90). After including covariates from the
      medical/social domain, significant correlations were established between faster
      mobility tests and better cognitive flexibility (TUG: r=0.565; 10MWT: r=0.324).
      Between groups comparisons also revealed that faster individuals in mobility
      tests presented higher physical fitness levels (aerobic: 0.49<g<0.77, strength:
      0.34<g<1.31). Significant correlations were found between better physical fitness
      and better cognitive flexibility (strength: r=-0.380; VO2 peak: r=-0.325) even
      after including age, education, fat-free mass and gender as covariates. These
      results suggest that the TUG and the 10MWT could potentially help distinguish
      individuals with poor neuromuscular, aerobic and cognitive flexibility
      performances. 

PMID- 24012564
TI  - Influenza vaccination in Austria from 1982 to 2011: a country resistant to
      influenza prevention and control.
AB  - BACKGROUND: Austria's position on influenza vaccination is unique. Generally it
      is recommended for everyone, and specifically for those over the age of 50 years
      and all children between 6 months and 5 years. However, the vaccination rate
      among the general public is one of the lowest in the world (<10%). Our objective
      was to provide baseline information to allow a better understanding of the low
      vaccination rate. METHODS: This paper presents data on influenza vaccine use in
      Austria during a period of almost 30 years, from 1982 to 2011. Data presented in
      this study were obtained from three sources. RESULTS: Between 1982 and 1992,
      Austria showed little change in its low proportion of vaccinations (from 20 to 23
      doses/1000); from 1992 to 1995, the proportion increased to 52 doses/1000,
      retaining its status as one of the low-use countries. By 2003, the proportion had
      increased to 127 doses/1000, but Austria remained one of the three lowest-use
      Western European countries. Between 2007 and 2011/2012, a steady decrease to 81
      doses/1000 was observed. CONCLUSION: The Austrian population, and parts of the
      medical system, have shown distinct ignorance regarding the prevention and
      control of influenza over past decades. Possible reasons for this development are
      discussed.

PMID- 24012565
TI  - HPV vaccination among French girls and women aged 14-23 years and the
      relationship with their mothers' uptake of Pap smear screening: a study in
      general practice.
AB  - INTRODUCTION: HPV vaccination is recommended in France for girls aged 14 and for
      those aged 15-23 before sexual debut or who have become sexually active within
      the previous year. The first aim was to describe vaccination practice among 14-23
      year-old girls visiting a general practitioner. A second objective was to
      investigate factors associated with starting vaccination among girls aged 14-18,
      in particular the regular practice of Pap-smear screening (PSS) by their mothers.
      METHODS: A cross-sectional study was conducted from June to August 2009. A total
      of 87 general practitioners from the large Rhone-Alpes region contributed data on
      502 girls/women who came for consultation. RESULTS: 231 (46.0%) of these
      girls/women had begun the process of HPV vaccination (68.2%, 56.9% and 18.7% of
      the 14-16, 17-20 and 21-23-year-olds respectively) of whom 139 (60.2%) had
      received all three doses. 92 girls/women (39.8%) had received only one or two
      doses at the time of study. However, in 71 (77.2%) cases, the gap between the
      last dose received and the time of study was within the between-dose interval
      recommended in the vaccination schedule. GPs reported that 16 (11.5%) had
      mentioned side effects following injections. Having a mother who practised
      regular PSS (Odds Ratio 6.2 [1.5-25.8]), having never lived with a partner (4.6
      [1.6-13.5]) and vaccination against hepatitis B (3.2 [1.6-6.1]) were found to be
      independently correlated with the initiation of HPV vaccination among girls/women
      aged 14-18 years. CONCLUSION: Two years after the start of the programme, only
      half of girls/women aged 14-23 years had begun the process of HPV vaccination.
      HPV vaccination status was correlated with PSS in the mother, family status and
      hepatitis B vaccination. Such information may help to better target girls who are
      less likely to be vaccinated.

PMID- 24012567
TI  - Preliminary data on immunogenicity, safety and tolerability of trivalent
      inactivated influenza vaccine in children with inborn errors of metabolism at
      risk of decompensation.
AB  - In order to evaluate the immunogenicity, safety and tolerability of influenza
      vaccination in children with inborn errors of metabolism (IEMs), we enrolled 20
      patients with IEMs at risk of decompensation (14 males; mean age+/-SD, 8.5+/
      3.9years) and 20 healthy age- and gender-matched controls. Four weeks after
      vaccination, seroconversion rates were 75-85% and seroprotection rates 85-95%,
      with high geometric mean titers (GMTs) of all three influenza antigen strains in
      both groups. Three months after vaccination, most of the subjects remained
      seroconverted with high seroprotection rates and high GMTs for all the three
      influenza strains. Safety and tolerability were also very good, with no
      differences between the groups. 

PMID- 24012566
TI  - Immunisation with ID83 fusion protein induces antigen-specific cell mediated and
      humoral immune responses in cattle.
AB  - In this study we have investigated the potential of mycobacterial proteins as
      candidate subunit vaccines for bovine tuberculosis. In addition, we have explored
      the use of TLR-ligands as potential adjuvants in cattle. In vitro screening
      assays with whole blood from Mycobacterium bovis-infected and BCG-vaccinated
      cattle demonstrated that fusion protein constructs were most commonly recognised,
      and the ID83 fusion protein was selected for further immunisation studies.
      Furthermore, glucopyranosyl lipid A (GLA) and resiquimod (R848), agonists for
      TLR4 and TLR7/8 respectively, stimulated cytokine production (IL-12, TNF-alpha,
      MIP-1beta and IL-10) in bovine dendritic cell cultures, and these were formulated
      as novel oil-in-water emulsions (GLA-SE and R848-SE) for immunisation studies.
      Immunisation with ID83 in a water-in-oil emulsion adjuvant (ISA70) induced both
      cell mediated and humoral immune responses, as characterised by antigen-specific
      IFN-gamma production, cell proliferation, IgG1 and IgG2 antibody production. In
      comparison, ID83 immunisation with the novel adjuvants induced weaker (ID83/R848
      SE) or no (ID83/GLA-SE) antigen-specific IFN-gamma production and cell
      proliferation. However, both did induce ID83-specific antibody production, which
      was restricted to IgG1 antibody isotype. Overall, these results provide
      encouraging preliminary data for the further development of ID83 in vaccine
      strategies for bovine TB. 

PMID- 24012568
TI  - New attenuated vaccine against columnaris disease in fish: choosing the right
      parental strain is critical for vaccine efficacy.
AB  - Flavobacterium columnare, the causative agent of columnaris disease, is a highly
      diverse species comprised by three genomovars. Genomovar II strains are more
      virulent toward catfishes than genomovar I isolates. The objective of this study
      was to compare the vaccine efficacy of avirulent mutants derived from genomovars
      I and II using a rifampicin-resistance strategy. First, we compared the efficacy
      of 13 genomovar II mutants in channel catfish (Ictalurus punctatus) fingerlings
      and identified mutant 17-23 as the best vaccine candidate based on their relative
      percent survival (RPS) against a highly virulent genomovar II strain (BGFS-27).
      In the second experiment, we vaccinated zebrafish (Danio rerio) with two
      genomovar II mutants (17-23 and 16-534) and FCRR (genomovar I mutant) followed by
      exposure to BGFS-27 strain. RPS values were 28.4, 20.3 and 8.1% for 17-23, 16
      534, and FCRR, respectively. For experiments 3 and 4, we tested both 17-23 and
      FCRR in channel catfish fry and Nile tilapia (Oreochromis niloticus). In both
      experiments, vaccinated fish were divided in two groups and each challenged with
      either a genomovar I (ARS-1) or a II (BGFS-27) strain. Channel catfish fry
      vaccinated with 17-23 and FCRR followed by challenge with BGFS-27 resulted in RPS
      values of 37.0% and 4.4%. When fish were challenged with ARS-1, RPS values were
      90.9% and 72.7% for fish vaccinated with 17-23 and FCRR, respectively. Nile
      tilapia vaccinated with 17-23 and FCRR followed by challenged with BGFS-27 had
      RPS values of 82.1% and 16.1%, respectively. When fish were challenged with
      strain ARS-1, RPS values were 86.9% and 75.5%. Overall, our results demonstrated
      that vaccination with genomovar II mutant 17-23 confers better protection in
      channel catfish and Nile tilapia than FCRR against columnaris disease caused by
      genomovar II. Both mutants were equally protective against columnaris caused by
      genomovar I showing that 17-23 mutant cross-protected against both genomovars. 

PMID- 24012569
TI  - A Salmonella Enteritidis hilAssrAfliG deletion mutant is a safe live vaccine
      strain that confers protection against colonization by Salmonella Enteritidis in
      broilers.
AB  - Consumption of contaminated poultry meat is an important cause of Salmonella
      infections in humans. Therefore, there is a need for control methods that protect
      broilers from day-of-hatch until slaughter age against infection with Salmonella.
      Colonization-inhibition, a concept in which a live Salmonella strain is orally
      administered to day-old chickens and protects against subsequent challenge, can
      potentially be used as control method. In this study, the safety and efficacy of
      a Salmonella Enteritidis DeltahilAssrAfliG strain as a colonization-inhibition
      strain for protection of broilers against Salmonella Enteritidis was evaluated.
      After administration of the Salmonella Enteritidis DeltahilAssrAfliG strain to
      day-old chickens, this strain could not be isolated from the gut, internal organs
      or faeces after 21 days of age. In addition, administration of this strain to one
      day-old broiler chickens decreased faecal shedding and caecal and internal organ
      colonization of a Salmonella Enteritidis challenge strain administered one day
      later using a seeder bird model. To our knowledge, this is the first report of an
      attenuated Salmonella strain for which both the safety and efficacy has been
      shown in long-term experiments (until slaughter age) in broiler strain can
      potentially be used as a live colonization-inhibition strain for controlling
      Salmonella Enteritidis infections in broilers. 

PMID- 24012570
TI  - Outer membrane vesicles derived from Bordetella parapertussis as an acellular
      vaccine against Bordetella parapertussis and Bordetella pertussis infection.
AB  - Bordetella parapertussis, a close related species of B. pertussis, can also cause
      the disease named pertussis or whooping cough. The number of cases caused by this
      related pathogen has risen sustained in the last years. The widely used cellular
      (wP) or acellular (aP) pertussis vaccines have little or no efficacy against B.
      parapertussis. In an effort to devise an effective acellular vaccine against B.
      parapertussis infection, outer membrane vesicles (OMVs) were obtained from B.
      parapertussis. Proteomic analysis of the resulting OMVs, designated OMVsBpp,
      evidenced the presence of several surface immunogens including pertactin. The
      characterized OMVsBpp were used in murine B. parapertussis intranasal challenge
      model to examine their protective capacity when administered by systemic route.
      Immunized BALB/c mice were challenged with sublethal doses of B. parapertussis.
      Significant differences between immunized animals and the negative control group
      were observed (p<0.001). OMVsBpp protected against B. parapertussis infection,
      whereas current commercial aP vaccine showed little protection against such
      pathogen. More interestingly, protection induced by OMVsBpp against B. pertussis
      was comparable to our previously designed vaccine consisting in OMVs derived from
      B. pertussis (OMVsBp). For these experiments we used as a positive control the
      current commercial aP vaccine in high dose. As expected aP offered protection
      against B. pertussis in mice. Altogether the results presented here showed that
      the OMVs from B. parapertussis are an attractive vaccine candidate to protect
      against whooping cough induced by B. parapertussis but also by B. pertussis. 

PMID- 24012571
TI  - Protective efficacy of PLGA microspheres loaded with divalent DNA vaccine
      encoding the ompA gene of Aeromonas veronii and the hly gene of Aeromonas
      hydrophila in mice.
AB  - In the present study, poly (lactic-co-glycolic) acid (PLGA) was used as a carrier
      for a divalent fusion DNA vaccine encoding the Aeromonas veronii outer membrane
      protein A (ompA) and Aeromonas hydrophila hemolysins (hly) protein. The
      recombinant pET-28a-ompA-hly was constructed by inserting the ompA gene and hly
      gene into a pET-28a expression vector. Loading of ompA-hly antigen module on PLGA
      microspheres were accomplished by water-in-oil-in-water (W/O/W) encapsulation.
      The molecular weight and specificity of pET-28a-ompA-hly were detected by dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The
      microspheres showed an average particle size of 100-150 MUm and a loading
      efficiency (LE) of 68.8%. Mice received ompA-hly antigen-loaded PLGA microspheres
      by intraperitoneal or intragastric administration mounted strong and sustained
      IgG response, which was significantly higher (p<0.05) than those achieved by pET
      28a-ompA-hly antigen alone. OmpA-hly antigen-loaded PLGA microsphere vaccine
      uniquely conferred a long lasting (30 days) sterile immunity against challenge
      infection. Results indicated that ompA-hly antigen-loaded PLGA microsphere
      vaccine is a qualified candidate vector system for sterile protective immunity
      against A. hydrophila and A. veronii infections.

PMID- 24012572
TI  - What is excellent science and how does it relate to what we publish in vaccine?

PMID- 24012573
TI  - Antigens of the type-three secretion system of Aeromonas salmonicida subsp.
      salmonicida prevent protective immunity in rainbow trout.
AB  - Aeromonas salmonicida subsp. salmonicida is the etiologic agent of furunculosis,
      a frequent and significant disease of fisheries worldwide. The disease is largely
      controlled by commercial oil adjuvanted vaccines containing bacterins. However,
      the mechanisms leading to a protective immune response remain poorly understood.
      The type-three secretion system (T3SS) plays a central role in virulence of A.
      salmonicida subsp. salmonicida and thus may have an influence on the immune
      response of the host. The aim of this study was to evaluate the role of the T3SS
      antigens in mounting a protective immune response against furunculosis. Rainbow
      trout were intraperitoneally vaccinated in two independent experiments with
      bacterins prepared from a wild-type A. salmonicida strain and an isogenic strain
      carrying a deletion in the T3SS (DeltaascV). Fish were challenged with the wt
      strain eight weeks after vaccination. In both trials, the survival rate of trout
      vaccinated with the DeltaascV strain was significantly higher (23-28%) in
      comparison to the group vaccinated with the wt strain. High-throughput proteomics
      analysis of whole bacteria showed the ascV deletion in the mutant strain resulted
      in lower expression of all the components of the T3SS, several of which have a
      potential immunosuppressive activity. In a third experiment, fish were vaccinated
      with recombinant AcrV (homologous to the protective antigen LcrV of Yersinia) or
      S-layer protein VapA (control). AcrV vaccinated fish were not protected against a
      challenge while fish vaccinated with VapA were partially protected. The presence
      of T3SS proteins in the vaccine preparations decreased the level of protection
      against A. salmonicida infection and that AcrV was not a protective antigen.
      These results challenge the hypothesis that mounting specific antibodies against
      T3SS proteins should bring better protection to fish and demonstrate that further
      investigations are needed to better understand the mechanisms underlying
      effective immune responses against A. salmonicida infection. 

PMID- 24012574
TI  - Efficacy and effectiveness of seasonal and pandemic A (H1N1) 2009 influenza
      vaccines in low and middle income countries: a systematic review and meta
      analysis.
AB  - PURPOSE: Influenza vaccines have been recommended for populations at risk for
      severe infection in low and middle income countries (LMICs) although knowledge of
      the evidence-base for their effectiveness and efficacy is limited in these
      countries. The aim of this systematic review is to provide an overview of the
      evidence-base for the effectiveness and efficacy of influenza vaccines in LMICs
      and to explore critical knowledge gaps. METHODS: PubMed, EMBASE, and Cochrane
      were searched for seasonal and pandemic A (H1N1) 2009 influenza vaccine
      effectiveness and efficacy studies performed in LMICs. Eligible studies included
      RCTs and observational studies, published in English, French, Spanish or
      Portuguese between 1960 and 2011, which assessed laboratory-confirmed influenza
      and/or influenza-related outcomes in any population. Risk of bias was assessed by
      two reviewers independently. Random effects pooled estimates were obtained when
      sufficient data were available. RESULTS: A total of 6465 articles were screened.
      Forty-one studies were included on seasonal influenza vaccine effectiveness and
      efficacy and one study on pandemic vaccine effectiveness. In middle income
      countries (MICs), efficacy of seasonal influenza vaccines was shown against
      laboratory-confirmed influenza in children (pooled efficacy 72% (95%CI: 65-77)
      and 81% (95%CI: 69-89), for one and two years follow-up respectively) and in the
      elderly (pooled efficacy 43% (95%CI: 25-56) and 58% (95%CI: 23-78), for live
      attenuated and inactivated vaccine respectively). Inactivated influenza vaccines
      were also found to be effective against cardiovascular outcomes in patients with
      coronary syndromes. CONCLUSIONS: Seasonal influenza vaccines can provide
      protection in children, the elderly and patients with coronary syndromes in MICs,
      and seem to be equally effective as compared to high income countries. Data for
      other high risk groups and from low income countries were limited or prone to
      bias, and are needed to further facilitate evidence-based decision making
      regarding influenza vaccination in LMICs.

PMID- 24012575
TI  - Bilateral bucket handle medial meniscal tears of the knee: A case report.
AB  - INTRODUCTION: Meniscal tears may cause knee pain and functional impairment.
      Bilateral bucket-handle meniscal tears is an uncommon condition. PRESENTATION OF
      CASE: This report presents the case of a 35-year-old male patient with bilateral
      bucket handle medial meniscal tears that occurred nonsimultaneously. The lesions
      were treated arthroscopically with partial resection in one knee and meniscal
      suture in the other. DISCUSSION: Bucket handle meniscal tear of meniscus without
      underlying meniscal, ligamentous pathology or lower limb deformity is a rare
      condition. CONCLUSION: To our knowledge, bilateral bucket handle medial meniscal
      tears without underlying meniscal anomalies have been reported in only two cases
      before, and our case is the third one.

PMID- 24012576
TI  - Rhizarthrosis fourth grade of eaton with hyperextension of the
      metacarpophalangeal joint.
AB  - INTRODUCTION: Restoration of thumb function with a painfree, stable, and mobile
      joint with preserved strength are the main goals of treatment of painful
      arthritis of the thumb. We present our clinical experience in surgical treatment
      of this disease, in its highest degree of affectation. PRESENTATION OF CASE: A 57
      year-old woman presents with a 2-year history of worsening pain at the base of
      her right, dominant, trapezial-metacarpal (TM) joint. Her thumb
      metacarpophalangeal (MCP) joint hyperextends 30 degrees  with lateral pinch.
      Radiographs demonstrate Eaton stage IV degenerative changes of her TM joint and
      no arthritis of her thumb MCP joint. She was successfully treated with a modified
      Burton-Pellegrini arthroplasty and sesamoidesis to the metacarpal head.
      DISCUSSION: In cases of advanced rhizarthrosis conventional surgery does not
      serve to correct deformities of the metacarpophalangeal joint that may affect to
      the postsurgical outcomes. CONCLUSION: rhizarthrosis management must be carried
      out in a global way. When a surgical treatment is planned, all deformities must
      be taken into account.

PMID- 24012577
TI  - Successful management of presacral ganglioneuroma: A case report and a review of
      the literature.
AB  - INTRODUCTION: Presacral ganglioneuromas are rare, usually benign lesions.
      Patients typically present when the mass is very large and becomes symptomatic.
      PRESENTATION OF CASE: This report describes the case of a 42 year old lady
      presenting with back pain who was subsequently diagnosed with a presacral
      ganglioneuroma based on MR imaging and a CT guided biopsy of the lesion.
      DISCUSSION: After counselling regarding nonoperative management, the patient
      opted for surgical resection. Open resection was performed with preservation of
      the neurovascular pelvic anatomy and an uneventful postoperative recovery. A
      review of the relevant literature was also performed using a search strategy in
      the online literature databases PUBMED and EMBASE. CONCLUSION: Surgical resection
      of a presacral ganglioneuroma is reasonable given their propensity for local
      effects and reported potential malignant transformation.

PMID- 24012578
TI  - An electrochemical DNA biosensor based on gold nanorods decorated graphene oxide
      sheets for sensing platform.
AB  - A simple electrochemical sensor for sensitive and selective DNA detection was
      constructed based on gold nanorods (Au NRs) decorated graphene oxide (GO) sheets.
      The high-quality Au NRs-GO nanocomposite was synthesized via the electrostatic
      self-assembly technique, which is considered a potential sensing platform.
      Differential pulse voltammetry was used to monitor the DNA hybridization event
      using methylene blue as an electrochemical indicator. Under optimal conditions,
      the peak currents of methylene blue were linear with the logarithm of the
      concentrations of complementary DNA from 1.0 * 10(-9) to 1.0 * 10(-14)M with a
      detection limit of 3.5 * 10(-15)M (signal/noise=3). Moreover, the prepared
      electrochemical sensor can effectively distinguish complementary DNA sequences in
      the presence of a large amount of single-base mismatched DNA (1000:1), indicating
      that the biosensor has high selectivity.

PMID- 24012580
TI  - Adverse health outcomes associated with surgical management of the small renal
      mass.
AB  - PURPOSE: Partial and radical nephrectomy are treatments for the small renal mass.
      Partial nephrectomy is considered the gold standard as it may protect against
      renal dysfunction compared to radical nephrectomy. However, both treatments may
      cause adverse health outcomes. MATERIALS AND METHODS: A matched cohort study was
      performed using the SEER (Surveillance, Epidemiology and End Results)-Medicare
      data set. Individuals treated with partial or radical nephrectomy for 4 cm or
      smaller nonmetastatic renal cell carcinoma were compared to 2 control groups
      (nonmuscle invasive bladder cancer and noncancer). A greedy algorithm matched
      surgical groups to controls. Medicare claims were examined for renal,
      cardiovascular and secondary cancer events. RESULTS: Patients who underwent
      partial nephrectomy (1,471) and radical nephrectomy (4,299) were matched to
      controls. The time to event model demonstrated an increased risk of renal events
      for both treatments. Compared to the bladder cancer control and noncancer control
      groups, radical nephrectomy hazard ratios for renal events were 2.415 (p <0.0001)
      and 6.211 (p <0.0001), respectively, while partial nephrectomy hazard ratios were
      1.513 (p <0.0001) and 4.926 (p <0.0001), respectively. Secondary cancers were
      increased for partial nephrectomy and radical nephrectomy compared to both
      control groups (p <0.0001). Cardiovascular events were increased for both
      treatments compared to noncancer controls (p <0.0001), but not compared to
      bladder cancer controls. CONCLUSIONS: Partial nephrectomy and radical nephrectomy
      may lead to adverse health outcomes. Compared to controls, partial nephrectomy
      and radical nephrectomy are associated with worsened renal outcomes. The increase
      in secondary cancers and cardiovascular events with both treatments is notable,
      and requires further investigation. Further research should investigate if active
      surveillance of the appropriately selected small renal mass limits adverse health
      outcomes.

PMID- 24012579
TI  - A randomized trial of cognitive rehabilitation in cancer survivors.
AB  - AIMS: The second most frequently reported post-treatment symptom in cancer
      survivors are concerns about impaired cognition. Despite numerous studies
      demonstrating significant impairments in a portion of survivors, information on
      effective treatments remains an emerging area of research. This study examined
      the effectiveness of a group-based cognitive rehabilitation intervention in
      cancer survivors. MAIN METHODS: This study was a randomized, controlled study of
      a 7-week cognitive rehabilitation intervention delivered in group format.
      Participants were evaluated with subjective symptom questionnaires and objective
      neurocognitive tests prior to and following treatment. KEY FINDINGS: Twenty-eight
      participants (mean age 58 years) with a median of 3 years (+/- 6 years) post
      primary/adjuvant treatment and various cancer sites (breast, bladder, prostate,
      colon, uterine) completed the study. Compared to baseline, the treatment group
      demonstrated improvements in symptoms of perceived cognitive impairments (p<.01),
      cognitive abilities (p<.01) and overall quality of life with regard to cognitive
      symptoms (p<.01) as measured by the FACT-Cog. The treatment group also improved
      on objective measures of attention (p<.05) and a trend toward improvement on
      verbal memory. Significant improvement was not observed on all cognitive tests.
      SIGNIFICANCE: A group based cognitive rehabilitation intervention in cancer
      survivors was effective for improving attention abilities and overall quality of
      life related to cognition. Results suggest that group based cognitive
      rehabilitation may be an effective intervention for treating cognitive
      dysfunction in cancer patients and should be further studied in a larger trial
      with an active control condition.

PMID- 24012581
TI  - Immunofluorescent analysis of testicular biopsies with germ cell and Sertoli cell
      markers shows significant MVH negative germ cell depletion with older age at
      orchiopexy.
AB  - PURPOSE: Undescended testis is the most common defect in male newborns. This
      condition is associated with increased risks of infertility and testicular
      malignancy due to abnormal germ cell development in the testes. Early surgery may
      limit such risks. We analyzed germ cell development vs age at orchiopexy using a
      germ cell marker and a Sertoli cell marker on testicular biopsies. MATERIALS AND
      METHODS: A total of 22 testicular biopsies at orchiopexy in 20 patients 5 to 24.5
      months old were fixed and embedded in paraffin. Sections were processed and
      labeled with AMH antibody for Sertoli cells and MVH antibody for germ cells for
      immunofluorescent histochemical analysis. Confocal images were counted using
      ImageJ (National Institutes of Health, Bethesda, Maryland) for germ cells and
      testicular tubules. The data were analyzed using linear regression. RESULTS:
      Sertoli cells were clearly distinguished from MVH positive and negative germ
      cells located centrally or on basement membranes of tubules. Percentage of
      tubules with MVH negative germ cells significantly decreased with increasing age
      at orchiopexy (beta = -0.03, p = 0.03). Total tubular numbers and "empty" tubules
      without germ cells significantly increased with age at orchiopexy (beta = 1.15, p
      = 0.02 and beta = 0.44, p = 0.04, respectively). CONCLUSIONS: AMH antibody
      distinguished Sertoli cells from germ cells, and MVH antibody distinguished 2
      types of germ cells at different developmental stages. Biopsy at orchiopexy in
      older patients showed significant germ cell depletion. These results lend support
      to early surgery to optimize germ cell number.

PMID- 24012583
TI  - Histotripsy of the prostate using a commercial system in a canine model.
AB  - PURPOSE: Histotripsy is a focused ultrasound technology that uses controlled
      acoustic cavitation to homogenize targeted tissue. We assessed local and systemic
      effects after histotripsy treatment with the Vortx RX(r) system in a canine
      model. The system was not approved for human use at the time of the study.
      MATERIALS AND METHODS: Histotripsy was applied in 10 intact male dogs. The
      therapy transducer (36 elements, 700 kHz and 11 cm focal distance) delivered
      acoustic bursts (3 cycles and 500 Hz pulse repetition frequency) transabdominally
      to the prostate for 60 minutes. Tissue and systemic response were assessed by
      transrectal ultrasound, cystoscopy and interval evaluation of blood and urine
      parameters. Prostates were harvested on postoperative day 2 in 2 dogs and on
      postoperative day 28 in 8. RESULTS: A treatment cavity was apparent in each
      prostate on transrectal ultrasound and cystoscopy. Mean prostate volume decreased
      36% (range 19% to 53%) by postoperative day 28. Although clinical symptoms were
      not produced, notable pathological findings at necropsy consisted of rectal wall
      muscle degeneration in 2 animals and concern for a potential histotripsy effect
      and 1 cm diameter areas of fibrosis in the abdominal rectus muscle in 2 animals
      suggestive of thermal injury along the acoustic propagation path to the prostate.
      CONCLUSIONS: Extracorporeal application of histotripsy produced prostate
      debulking in all dogs. Pathological findings of collateral injury are of concern
      since this may represent suboptimal confinement of cavitation or heating of
      overlying tissue. Further study is under way to quantify the prefocal thermal
      fields to eliminate these effects before human application.

PMID- 24012582
TI  - New contralateral vesicoureteral reflux after unilateral ureteral reimplantation:
      predictive factors and clinical outcomes.
AB  - PURPOSE: Although unilateral ureteral reimplantation for vesicoureteral reflux is
      highly successful, new contralateral reflux will develop postoperatively in some
      patients. We examined predictors and clinical outcomes of postoperative
      contralateral vesicoureteral reflux. MATERIALS AND METHODS: We reviewed patients
      who underwent nontapered unilateral reimplantation for primary vesicoureteral
      reflux graded on a 3-point scale at our institution from January 1990 to December
      2002, and identified those with subsequent contralateral vesicoureteral reflux.
      We analyzed the association of patient/procedure characteristics with incidence,
      and time to resolution of contralateral reflux and postoperative urinary tract
      infection. Multivariable models controlled for variables associated with
      incidence and time to resolution of contralateral reflux. RESULTS: A total of 395
      patients (77.2% female, median age 5.3 years) underwent ureteral reimplantation
      for vesicoureteral reflux. Preoperative reflux was grade 1 in 2.8% of patients,
      grade 2 in 56.6% and grade 3 in 40.6%. Technical success was 95.4%. After
      reimplantation 39 patients (9.9%) had new contralateral reflux (grade 1 in 7,
      grade 2 in 27 and grade 3 in 5). Median followup was 51.8 months. On multivariate
      analysis younger age (less than 6 years, OR 3.7, p = 0.006) and low observed
      bladder capacity as percent of predicted bladder capacity (less than 50% of
      predicted capacity, OR 6.3, p = 0.02) were significant predictors of
      contralateral reflux. Contralateral reflux resolved in 21 of 27 patients (77.8%)
      on subsequent cystography at a median of 21.5 months. Two patients underwent
      reimplantation for persistent contralateral reflux. Four of 39 patients (10.3%)
      with contralateral reflux had postoperative febrile urinary tract infections at a
      median of 26 months, with spontaneous resolution of contralateral reflux in all.
      CONCLUSIONS: Younger patients and those with low observed vs predicted bladder
      capacity may be at increased risk for postoperative contralateral vesicoureteral
      reflux. A majority of contralateral reflux will resolve spontaneously, and the
      clinical course is typically benign.

PMID- 24012584
TI  - Phylogeny and biogeography of the fruit doves (Aves: Columbidae).
AB  - We reconstruct the phylogeny of fruit doves (genus Ptilinopus) and allies with a
      dense sampling that includes almost all species, based on mitochondrial and
      nuclear sequence data. We evaluate the most likely biogeographic scenario for the
      evolution of this group that colonized many islands of the Pacific Ocean. We also
      investigate the evolution of one of the main plumage character of fruit doves
      (the color of the crown), and we propose several revisions of the group's
      systematics. All Ptilinopus taxa formed a monophyletic group that includes two
      morphologically distinct genera, Alectroenas and Drepanoptila, confirming a
      previous result found with less species and genes. The divergence time analysis
      suggests that the basal divergences within Ptilinopus dated to the Early
      Oligocene, and the biogeographic analysis indicates that fruit doves originated
      most probably from the proto New Guinea region. The earliest dispersals from the
      New Guinea region to Oceania occurred with the colonization of New Caledonia and
      Fiji. A large group of Polynesian species (Central and Eastern), as well as the
      three taxa found in Micronesia and four species from the Guinean-Moluccan region,
      form the "purpuratus" clade, the largest diversification of fruit doves within
      Oceania, which also has a New Guinean origin. However, the eastbound colonization
      of fruit doves was not associated with a significant increase of their
      diversification rate. Overall, the Melanesian region did not act as a cradle for
      fruit doves, in contrast to the New Guinea region which is found as the ancestral
      area for several nodes within the phylogeny. 

PMID- 24012585
TI  - Associations of HLA class I antigen specificities and haplotypes with disease
      progression in HIV-1-infected Hans in Northern China.
AB  - The human leukocyte antigen (HLA) allele frequencies, which differ among various
      ethnic populations, may result in population-specific effects on HIV-1 disease
      progression. No large-scale study has yet been conducted on the Chinese
      population. In this study, HLA class I antigen specificities were determined in a
      cohort including 105 long-term non-progressors (LTNPs) and 321 typical
      progressors (TPs), who were recruited from HIV-1-infected Northern Han Chinese,
      to determine the associations between certain HLA types and HIV-1 disease
      progression. The frequencies of HLA class I specificities and haplotypes among
      the two groups were compared using binary logistic stepwise regression. Results
      showed that HLA-A(*)30-B(*)13-C(*)06 (OR = 0.387, P = 0.019) and B(*)67 (OR =
      0.134, P = 0.005) were associated with a long-term non-progressing condition, and
      C(*)01 (OR = 2.539, P = 0.050) was overrepresented in TPs after adjusting for non
      genetic factors (sex, age, the location of patients, HIV subtype and the route of
      infection). The influence of HLA homozygosity on HIV disease progression was also
      analyzed. However, homozygosity at HLA-A, HLA-B or HLA-C conferred no observable
      disadvantage in our study population (P = 0.730, 0.246 and 0.445, respectively).
      These findings suggest that the host's genetics make important contributions to
      HIV viral control and may help to develop peptide-based vaccines for this
      population.

PMID- 24012586
TI  - Treadmill training in moderate risk preterm infants promotes stepping quality-
      results of a small randomised controlled trial.
AB  - Infants at risk for neuromotor delay (NMD) are associated with premature birth
      and low birth weight. These infants frequently exhibit tone, posture, and
      movement abnormalities. Therefore, it is important to identify potential
      interventions to facilitate early motor development within this population. The
      purpose of this study was to examine the potential benefits of treadmill (TM)
      training in infants at risk for NMD. Furthermore, relationships between TM
      stepping performance and onset of walking have been suggested, and therefore,
      were also explored. Twenty-eight infants at moderate risk for NMD were randomly
      assigned to one of two groups: (1) TM training (experimental) (N=15) or (2)
      control (N=13). Infants in the experimental group were trained for 8 min/day,
      five days/week from study entry until walking onset. Monthly, 5 min of TM
      stepping performance were videotaped and analysed for infants in both groups to
      obtain frequency and quality of TM stepping. Groups were different in terms of TM
      stepping performance with experimental group displaying better stepping. However,
      they did not differ in age of walking onset (experimental=15.1 months,
      control=14.6 months). In both groups, frequency of TM stepping was significantly
      related to onset of walking. Findings suggest that TM training as implemented
      impact the quality of TM stepping, but did not significantly improve walking
      onset. Given the significant relationship between stepping and walking onset, the
      moderate affection of the population, the relative low intensity and lack of
      individualisation of the training, we suggest future research should further
      explore the impact of TM training on gait-related variables and include
      individualised, more intense, and prolonged training.

PMID- 24012587
TI  - The progression of severe behavior disorder in young children with intellectual
      and developmental disabilities.
AB  - Behavior disorders, such as self-injurious, stereotypic, and aggressive behavior
      are common among individuals with intellectual or developmental disabilities.
      While we have learned much about those behaviors over the past few decades,
      longitudinal research that looks at developmental trajectory has been rare. This
      study was designed to examine the trajectory of these three forms of severe
      behavior disorders over a one year time period. The behaviors were measured on
      two dimensions: frequency of occurrence and severity. Participants were 160
      infants and toddlers at risk for developmental delays in Lima, Peru. Using
      structural equation modeling, we found that the frequency of self-injury and
      stereotypic behavior and the severity of aggressive behavior remained stable over
      the 12-month period. Uni-directional structural models fit the data best for self
      injurious and aggressive behavior (with frequency being a leading indicator of
      future severity of self-injury and severity being a leading indicator of future
      frequency for aggression). For stereotypic behavior, a cross-lagged
      autoregressive model fit the data best, with both dimensions of frequency and
      severity involved as leading indicators of each other. These models did not vary
      significantly across diagnostic groups, suggesting that toddlers exhibiting
      behavior disorders may be assisted with interventions that target the specific
      frequencies or severities of behaviors, regardless of diagnostic category. 

PMID- 24012588
TI  - Deficit in implicit motor sequence learning among children and adolescents with
      spastic cerebral palsy.
AB  - Skill learning (SL) is learning as a result of repeated exposure and practice,
      which encompasses independent explicit (response to instructions) and implicit
      (response to hidden regularities) processes. Little is known about the effects of
      developmental disorders, such as Cerebral Palsy (CP), on the ability to acquire
      new skills. We compared performance of CP and typically developing (TD) children
      and adolescents in completing the serial reaction time (SRT) task, which is a
      motor sequence learning task, and examined the impact of various factors on this
      performance as indicative of the ability to acquire motor skills. While both
      groups improved in performance, participants with CP were significantly slower
      than TD controls and did not learn the implicit sequence. Our results indicate
      that SL in children and adolescents with CP is qualitatively and quantitatively
      different than that of their peers. Understanding the unique aspects of SL in
      children and adolescents with CP might help plan appropriate and efficient
      interventions. 

PMID- 24012589
TI  - Curcumin loaded poly(2-hydroxyethyl methacrylate) nanoparticles from gelled ionic
      liquid--in vitro cytotoxicity and anti-cancer activity in SKOV-3 cells.
AB  - The main focus of this study is to encapsulate hydrophobic drug curcumin in
      hydrophilic polymeric core such as poly(2-hydroxyethyl methacrylate) [PHEMA]
      nanoparticles from gelled ionic liquid (IL) to improve its efficacy. We have
      achieved 26.4% drug loading in a biocompatible hydrophilic polymer. Curcumin
      loaded PHEMA nanoparticles (C-PHEMA-NPs) were prepared by nano-precipitation
      method. Scanning electron microscopy (SEM) and atomic force microscopy (AFM)
      analysis showed that the prepared nanoparticles were spherical in shape and free
      from aggregation. The size and zeta potential of prepared C-PHEMA-NPs were about
      300 nm and -33.4 mV respectively. C-PHEMA-NPs were further characterized by FT-IR
      spectroscopy which confirmed the existence of curcumin in the nanoparticles. X
      ray diffraction and differential scanning calorimetry studies revealed that
      curcumin present in the PHEMA nanoparticles were found to be amorphous in nature.
      The anticancer activity of C-PHEMA-NPs was measured in ovarian cancer cells (SKOV
      3) in vitro, and the results revealed that the C-PHEMA-NPs had better tumor cells
      regression activity than free curcumin. Flow cytometry showed the significant
      reduction in G0/G1 cells after treatment with C-PHEMA-NPs and molecular level of
      apoptosis were also studied using western blotting. Toxicity of PHEMA
      nanoparticles were studied in zebrafish embryo model and results revealed the
      material to be highly biocompatible. The present study demonstrates the curcumin
      loaded PHEMA nanoparticles have potential therapeutic values in the treatment of
      cancer.

PMID- 24012590
TI  - Formulation and in vivo human bioavailability of dissolving tablets containing a
      self-nanoemulsifying itraconazole solid dispersion without precipitation in
      simulated gastrointestinal fluid.
AB  - To investigate the performance of a solid-state self-nanoemulsifying system with
      no precipitation in gastric and intestinal fluid, itraconazole (ITZ) was selected
      as a model drug because of its practically insoluble nature in intestinal fluid.
      A self-nanoemulsifying ITZ solid dispersion (SNESD) system was prepared as
      follows: (1) establishment of self-nanoemulsifying composition via the hot
      melting method, (2) solidification with fumed silicon dioxide (Aerosil 300) via
      adsorption to prepare SNESD and (3) preparation of a directly compressible tablet
      containing SNESD. This SNESD was easily formulated in the form of a dissolving
      tablet and provided a favourable nanoemulsifying microenvironment with no
      precipitation in the testing media. The SNESD and SNESD-loaded tablet displayed
      highly enhanced dissolution via nanomisation (266.8 nm and 258.3 nm at 60 min and
      120 min, respectively), whereas the drug alone or a reference ITZ Sporanox(r)
      capsule displayed very low dissolution and precipitated immediately in intestinal
      fluid. Drug precipitation in intestinal fluid may affect the in vivo performance
      of poorly soluble weakly basic drugs and was estimated according to the crystal
      growth theory. The superdisintegrant and surfactant in the formulation of the
      tablet were very crucial to the dissolution of the SNESD-loaded tablet. The drug
      contents and dissolution rates of the SNESD-loaded tablets were also stable
      during storage in terms of dissolution and drug content. The SNESD-loaded tablet
      displayed significantly increased oral bioavailability in healthy human
      volunteers compared with the reference Sporanox(r) capsule. The current solid
      state SNESD-loaded tablet could provide an alternative to liquid-based
      emulsifying preparations for various poorly water-soluble drugs without
      precipitation in testing media.

PMID- 24012591
TI  - Hydrogen sulfide-mediated stimulation of mitochondrial electron transport
      involves inhibition of the mitochondrial phosphodiesterase 2A, elevation of cAMP
      and activation of protein kinase A.
AB  - Although hydrogen sulfide (H2S) is generally known as a mitochondrial poison,
      recent studies show that lower concentrations of H2S play a physiological role in
      the stimulation of mitochondrial electron transport and cellular bioenergetics.
      This effect involves electron donation at Complex II. Other lines of recent
      studies demonstrated that one of the biological actions of H2S involves
      inhibition of cAMP and cGMP phosphodiesterases (PDEs). Given the emerging
      functional role of the mitochondrial isoform of cAMP PDE (PDE2A) in the
      regulation of mitochondrial function the current study investigated whether cAMP
      dependent mechanisms participate in the stimulatory effect of NaHS on
      mitochondrial function. In isolated rat liver mitochondria, partial digestion
      studies localized PDE2A into the mitochondrial matrix. NaHS exerted a
      concentration-dependent inhibitory effect on recombinant PDE2A enzyme in vitro.
      Moreover, NaHS induced an elevation of cAMP levels when added to isolated
      mitochondria and stimulated the mitochondrial electron transport. The latter
      effect was inhibited by Rp-cAMP, an inhibitor of the cAMP-dependent protein
      kinase (PKA). The current findings suggest that the direct electron donating
      effect of NaHS is amplified by an intramitochondrial cAMP system, which may
      involve the inhibition of PDE2A and subsequent, cAMP-mediated stimulation of PKA.

PMID- 24012592
TI  - Dendrite spines plasticity in brain disorders.

PMID- 24012593
TI  - Children with cerebral palsy have greater stochastic features present in the
      variability of their gait kinematics.
AB  - Children with CP have a more variable gait pattern. However, it is currently
      unknown if these variations arise from deterministic variations that are a result
      of a change in the motor command or stochastic features that are present in the
      nervous system. The aim of this investigation was to use a Langevin equation
      methodology to evaluate the deterministic and stochastic features that are
      present in the variability of the gait kinematics of children with cerebral palsy
      (CP). Ten children with spastic diplegic CP and nine typically developing (TD)
      children participated in this investigation. All of the children walked on a
      treadmill for 2 min while a three-dimensional motion capture system recorded the
      step kinematics. Our major findings for this investigation were: (1) children
      with CP had greater variability in their gait patterns than TD children, (2) the
      variability of the children with CP and TD children had similar deterministic
      features, (3) the variability had greater stochastic features for the children
      with CP, and (4) the increase in the amount of variability was strongly
      correlated with the increase in stochastic features. These results indicate that
      the variability seen in the gait patterns of children with CP may be due to the
      inability to suppress the noise that is present in the neuromuscular system.

PMID- 24012594
TI  - A Kinect-based upper limb rehabilitation system to assist people with cerebral
      palsy.
AB  - This study assessed the possibility of rehabilitating two adolescents with
      cerebral palsy (CP) using a Kinect-based system in a public school setting. The
      system provided 3 degrees of freedom for prescribing a rehabilitation program to
      achieve customized treatment. This study was carried out according to an ABAB
      reversal replication design in which A represented the baseline and B represented
      intervention phases. Data showed that the two participants significantly
      increased their motivation for upper limb rehabilitation, thus improving exercise
      performance during the intervention phases. Practical and developmental
      implications of the findings are discussed. 

PMID- 24012595
TI  - Mental health and social participation skills of wheelchair basketball players: a
      controlled study.
AB  - The aim of this study was to assess differences in psychological well-being,
      symptomatic psychological disorders and social participation, between competitive
      wheelchair basketball participants and those non-participants. Forty-six
      wheelchair participants, 24 Basketball players (aged 35.60 +/- 7.56) and 22 non
      players (aged 36.20 +/- 6.23), completed three validated self-report
      questionnaires: Participation Scale (PS), Psychological Well-Being Scale [PWBS]
      and Symptom Checklist 90 R [SCL-90-R]. ANOVA showed significant overall
      differences between the two groups. The social restriction score, evaluated by
      PS, was significantly higher in the non-basketball participants (p=0.00001) than
      the basketball participants. The PWB Scale showed significant differences in all
      6 dimensions: positive relations with others, environmental mastery, personal
      growth, purpose in life and self-acceptance (p<0.01), and autonomy (p<0.05), with
      better scores in the basketball participants. The SCL-90-R scores were
      significantly lower for the basketball group in the following 6 symptomatic
      dimensions: depression, phobic anxiety, and sleep disorder (p<0.01),
      somatization, interpersonal sensitivity and psychoticism (with p<0.05). It was
      concluded that competitive wheelchair basketball participants showed better
      psychological well-being and social skills than those non-participants.

PMID- 24012596
TI  - The effect of the degree of disability on nutritional status and flat feet in
      adolescents with Down syndrome.
AB  - Excessive weight and obesity are ranked among lifestyle diseases. In the case of
      weight gain, the effectiveness of therapy based on diet and physical activity
      depends considerably on patients themselves, but despite this the number of those
      who successfully manage to lose weight is still not satisfactory. Preventing or
      treating excessive weight gain in the intellectually disabled is extremely
      difficult since they have a higher risk for developing obesity. The below
      presented study assessed the effect of the degree of intellectual disability on
      nutritional status in adolescents with Down syndrome. It also focused on some
      correlations between the degree of disability and a selected constituent of the
      body posture, i.e. flat feet. A total of 54 males and 26 females with mild and
      moderate Down syndrome, aged 18.68 +/- 1.73, residents of Special Needs Education
      Centre in Tarnow, Poland, participated in the study, in which body weight and
      height, BMI, fat tissue percentage and the longitudinal arch of the foot were
      measured. A total of 17.5% of individuals with mild and 50% of individuals with
      moderate ID were found overweight or obese. Weight gain more often occurred in
      females. It seemed that flat feet were affected to a greater extent by the
      participants' nutritional status than their degree of disability. The study found
      no unambiguous effect of the degree of disability on the nutritional status and
      flat feet in individuals with Down syndrome.

PMID- 24012597
TI  - The relationship between physical appearance concerns, disgust, and anti-fat
      prejudice.
AB  - This study examined relationships between physical appearance concerns (fear of
      fat, body image disturbance; BIDQ), disgust, and anti-fat prejudice (dislike,
      blame), and tested whether disgust mediates relationships between physical
      appearance concerns and anti-fat prejudice. Participants (N=1649; age=28 years)
      provided demographic data and completed measures of anti-fat prejudice, tendency
      to feel disgust, and physical appearance concerns. Univariate, multivariate, and
      mediation analyses were conducted. Univariate and multivariate associations were
      found between fear of fat, BIDQ, disgust, and anti-fat prejudice for women. For
      women only, mediation analyses showed that disgust partially mediated
      relationships between physical appearance concerns and dislike of fat people. For
      men, univariate and multivariate relationships were found between fear of fat,
      and dislike and blame of fat people, but disgust was not related to anti-fat
      prejudice. Newer constructs centering on physical appearance concerns and disgust
      appear promising candidates for understanding anti-fat prejudice. 

PMID- 24012598
TI  - Environmental enrichment increases doublecortin-associated new neurons and
      decreases neuronal death without modifying anxiety-like behavior in mice
      chronically exposed to toluene.
AB  - Toluene misuse is a health problem worldwide with broad effects at the level of
      the central nervous system; however, therapeutic alternatives for inhalant
      abusers are limited. Chronic use of volatile substances is associated with
      different neurological and cognitive alterations, being anxiety a psychiatric
      condition with high prevalence. At cellular level toluene reduces neurogenesis
      and induces neuronal death. On the other hand, environmental enrichment has
      demonstrated to produce positive effects at behavioral and neuronal levels. Thus,
      the aim of the present work was to model alterations occasioned after repeated
      exposure to toluene (anxiety, reduction in neurogenesis - measured as
      doublecortin-labeled cells - and neuronal death). Subsequently, the influence of
      environmental enrichment on these effects was evaluated. Adolescent mice were
      exposed to toluene vapors from 1 to 4 weeks. Effects on anxiety were evaluated
      with the burying behavior test, whereas neurogenesis and hippocampal cell death
      were analyzed with immunohistochemistry, using anti-doublecortin or anti-active
      Caspase-3 antibodies, respectively. Results showed that chronic toluene exposure
      increased anxiety in the burying behavior test; additionally, toluene decreased
      neurogenesis and enhanced neuronal death. Environmental enrichment (EE) enhanced
      the anxiety like response in air-exposed mice but did not modify the toluene
      anxiety response. Additionally, EE enhanced neurogenesis in toluene-pretreated
      animals at the same level to that found in animals unexposed to toluene and
      decreased neuronal death. Overall, the present study showed that environmental
      enrichment positively impacts some effects produced by repeated exposure to
      toluene. 

PMID- 24012599
TI  - Polishing the craft of genetic diversity creation in directed evolution.
AB  - Genetic diversity creation is a core technology in directed evolution where a
      high quality mutant library is crucial to its success. Owing to its importance,
      the technology in genetic diversity creation has seen rapid development over the
      years and its application has diversified into other fields of scientific
      research. The advances in molecular cloning and mutagenesis since 2008 were
      reviewed. Specifically, new cloning techniques were classified based on their
      principles of complementary overhangs, homologous sequences, overlapping PCR and
      megaprimers and the advantages, drawbacks and performances of these methods were
      highlighted. New mutagenesis methods developed for random mutagenesis, focused
      mutagenesis and DNA recombination were surveyed. The technical requirements of
      these methods and the mutational spectra were compared and discussed with
      references to commonly used techniques. The trends of mutant library preparation
      were summarised. Challenges in genetic diversity creation were discussed with
      emphases on creating "smart" libraries, controlling the mutagenesis spectrum and
      specific challenges in each group of mutagenesis methods. An outline of the wider
      applications of genetic diversity creation includes genome engineering, viral
      evolution, metagenomics and a study of protein functions. The review ends with an
      outlook for genetic diversity creation and the prospective developments that can
      have future impact in this field. 

PMID- 24012600
TI  - Dynamic root growth and architecture responses to limiting nutrient availability:
      linking physiological models and experimentation.
AB  - In recent years the study of root phenotypic plasticity in response to sub
      optimal environmental factors and the genetic control of these responses have
      received renewed attention. As a path to increased productivity, in particular
      for low fertility soils, several applied research projects worldwide target the
      improvement of crop root traits both in plant breeding and biotechnology
      contexts. To assist these tasks and address the challenge of optimizing root
      growth and architecture for enhanced mineral resource use, the development of
      realistic simulation models is of great importance. We review this research field
      from a modeling perspective focusing particularly on nutrient acquisition
      strategies for crop production on low nitrogen and low phosphorous soils. Soil
      heterogeneity and the dynamics of nutrient availability in the soil pose a
      challenging environment in which plants have to forage efficiently for nutrients
      in order to maintain their internal nutrient homeostasis throughout their life
      cycle. Mathematical models assist in understanding plant growth strategies and
      associated root phenes that have potential to be tested and introduced in
      physiological breeding programs. At the same time, we stress that it is necessary
      to carefully consider model assumptions and development from a whole plant
      resource allocation perspective and to introduce or refine modules simulating
      explicitly root growth and architecture dynamics through ontogeny with reference
      to key factors that constrain root growth. In this view it is important to
      understand negative feedbacks such as plant-plant competition. We conclude by
      briefly touching on available and developing technologies for quantitative root
      phenotyping from lab to field, from quantification of partial root profiles in
      the field to 3D reconstruction of whole root systems. Finally, we discuss how
      these approaches can and should be tightly linked to modeling to explore the root
      phenome. 

PMID- 24012601
TI  - Antimicrobial peptides from the venom gland of the social wasp Vespa tropica.
AB  - Peptide agents are regarded as potential candidates for overcoming the life
      threatening resistance of pathogenic microorganisms to classic antibiotics.
      Accordingly, a peptidomic and genomic investigation of natural antimicrobial
      peptides (AMPs) can provide structure-functional information for designing
      peptide antibiotics with therapeutic potential. In the present study, we
      identified nine AMPs from the venom gland of the wasp Vespa tropica using
      combined methods of peptidomics and genomics. These AMPs were classified into two
      different families based on sequence similarity, mastoparan and vespid
      chemotactic peptides (VCPs), and thus named mastoparan-VT1 to -VT7, VCP-VT1 and 
      VT2. Among these nine AMPs, mastoparan-VT1 and VCP-VT1 are identical to peptides
      from other wasps. These AMPs exerted broad-spectrum antimicrobial activity
      against standard and clinically isolated strains of bacteria. In addition, they
      showed weak hemolytic activity toward human erythrocytes. Our results reveal that
      identical AMPs are widely distributed in different wasp venoms and might provide
      templates for the development of novel peptide antibiotics. 

PMID- 24012602
TI  - Mathematical modeling of the hypothalamic-pituitary-adrenal gland (HPA) axis,
      including hippocampal mechanisms.
AB  - This paper presents a mathematical model of the HPA axis. The HPA axis consists
      of the hypothalamus, the pituitary and the adrenal glands in which the three
      hormones CRH, ACTH and cortisol interact through receptor dynamics. Furthermore,
      it has been suggested that receptors in the hippocampus have an influence on the
      axis. A model is presented with three coupled, non-linear differential equations,
      with the hormones CRH, ACTH and cortisol as variables. The model includes the
      known features of the HPA axis, and includes the effects from the hippocampus
      through its impact on CRH in the hypothalamus. The model is investigated both
      analytically and numerically for oscillating solutions, related to the ultradian
      rhythm seen in data, and for multiple fixed points related to hypercortisolemic
      and hypocortisolemic depression. The existence of an attracting trapping region
      guarantees that solution curves stay non-negative and bounded, which can be
      interpreted as a mathematical formulation of homeostasis. No oscillating
      solutions are present when using physiologically reasonable parameter values.
      This indicates that the ultradian rhythm originate from different mechanisms.
      Using physiologically reasonable parameters, the system has a unique fixed point,
      and the system is globally stable. Therefore, solutions converge to the fixed
      point for all initial conditions. This is in agreement with cortisol levels
      returning to normal, after periods of mild stress, in healthy individuals.
      Perturbing parameters lead to a bifurcation, where two additional fixed points
      emerge. Thus, the system changes from having a unique stable fixed point into
      having three fixed points. Of the three fixed points, two are stable and one is
      unstable. Further investigations show that solutions converge to one of the two
      stable fixed points depending on the initial conditions. This could explain why
      healthy people becoming depressed usually fall into one of two groups: a
      hypercortisolemic depressive group or a hypocortisolemic depressive group. 

PMID- 24012603
TI  - Dynamic behavior of lactate values in venous-arterial extracorporeal membrane
      oxygenation for refractory cardiac arrest.

PMID- 24012604
TI  - Development of injectable organic/inorganic colloidal composite gels made of self
      assembling gelatin nanospheres and calcium phosphate nanocrystals.
AB  - Colloidal gels are a particularly attractive class of hydrogels for applications
      in regenerative medicine, and allow for a "bottom-up" fabrication of multi
      functional biomaterials by employing micro- or nanoscale particles as building
      blocks to assemble into shape-specific bulk scaffolds. So far, however, the
      synthesis of colloidal composite gels composed of both organic and inorganic
      particles has hardly been investigated. The current study has focused on the
      development of injectable colloidal organic-inorganic composite gels using
      calcium phosphate (CaP) nanoparticles and gelatin (Gel) nanospheres as building
      blocks. These novel Gel-CaP colloidal composite gels exhibited a strongly
      enhanced gel elasticity, shear-thinning and self-healing behavior, and gel
      stability at high ionic strengths, while chemical - potentially cytotoxic -
      functionalizations were not necessary to introduce sufficiently strong cohesive
      interactions. Moreover, it was shown in vitro that osteoconductive CaP
      nanoparticles can be used as an additional tool to reduce the degradation rate of
      otherwise fast-degradable gelatin nanospheres and fine-tune the control over the
      release of growth factors. Finally, it was shown that these colloidal composite
      gels support attachment, spreading and proliferation of cultured stem cells.
      Based on these results, it can be concluded that proof-of-principle has been
      obtained for the design of novel advanced composite materials made of nanoscale
      particulate building blocks which exhibit great potential for use in regenerative
      medicine. 

PMID- 24012605
TI  - Calcium phosphate deposition rate, structure and osteoconductivity on electrospun
      poly(l-lactic acid) matrix using electrodeposition or simulated body fluid
      incubation.
AB  - Mineralized nanofibrous scaffolds have been proposed as promising scaffolds for
      bone regeneration due to their ability to mimic both nanoscale architecture and
      chemical composition of natural bone extracellular matrix. In this study, a novel
      electrodeposition method was compared with an extensively explored simulated body
      fluid (SBF) incubation method in terms of the deposition rate, chemical
      composition and morphology of calcium phosphate formed on electrospun fibrous
      thin matrices with a fiber diameter in the range ~200-1400 nm prepared using 6,
      8, 10 and 12 wt.% poly(l-lactic acid) (PLLA) solutions in a mixture of
      dichloromethane and acetone (2:1 in volume). The effects of the surface
      modification using the two mineralization techniques on osteoblastic cell (MC3T3
      E1) proliferation and differentiation were also examined. It was found that
      electrodeposition was two to three orders of magnitude faster than the SBF method
      in mineralizing the fibrous matrices, reducing the mineralization time from ~2
      weeks to 1h to achieve the same amounts of mineralization. The mineralization
      rate also varied with the fiber diameter but in opposite directions between the
      two mineralization methods. As a general trend, the increase of fiber diameter
      resulted in a faster mineralization rate for the electrodeposition method but a
      slower mineralization rate for the SBF incubation method. Using the
      electrodeposition method, one can control the chemical composition and morphology
      of the calcium phosphate by varying the electric deposition potential and
      electrolyte temperature to tune the mixture of dicalcium phosphate dihydrate and
      hydroxyapatite (HAp). Using the SBF method, one can only obtain a low
      crystallinity HAp. The mineralized electrospun PLLA fibrous matrices from either
      method similarly facilitate the proliferation and osteogenic differentiation of
      preosteoblastic MC3T3-E1 cells as compared to neat PLLA matrices. Therefore, the
      electrodeposition method can be utilized as a fast and versatile technique to
      fabricate mineralized nanofibrous scaffolds for bone tissue engineering.

PMID- 24012606
TI  - Young developmental age cardiac extracellular matrix promotes the expansion of
      neonatal cardiomyocytes in vitro.
AB  - A major limitation to cardiac tissue engineering and regenerative medicine
      strategies is the lack of proliferation of postnatal cardiomyocytes. The
      extracellular matrix (ECM) is altered during heart development, and studies
      suggest that it plays an important role in regulating myocyte proliferation.
      Here, the effects of fetal, neonatal and adult cardiac ECM on the expansion of
      neonatal rat ventricular cells in vitro are studied. At 24h, overall cell
      attachment was lowest on fetal ECM; however, ~80% of the cells were
      cardiomyocytes, while many non-myocytes attached to older ECM and poly-l-lysine
      controls. After 5 days, the cardiomyocyte population remained highest on fetal
      ECM, with a 4-fold increase in number. Significantly more cardiomyocytes stained
      positively for the mitotic marker phospho-histone H3 on fetal ECM compared with
      other substrates at 5 days, suggesting that proliferation may be a major
      mechanism of cardiomyocyte expansion on young ECM. Further study of the
      beneficial properties of early developmental aged cardiac ECM could advance the
      design of novel biomaterials aimed at promoting cardiac regeneration.

PMID- 24012607
TI  - Vegetable-oil-based polymers as future polymeric biomaterials.
AB  - Vegetable oils are one of the most important classes of bio-resources for
      producing polymeric materials. The main components of vegetable oils are
      triglycerides - esters of glycerol with three fatty acids. Several highly
      reactive sites including double bonds, allylic positions and the ester groups are
      present in triglycerides from which a great variety of polymers with different
      structures and functionalities can be prepared. Vegetable-oil-based polyurethane,
      polyester, polyether and polyolefin are the four most important classes of
      polymers, many of which have excellent biocompatibilities and unique properties
      including shape memory. In view of these characteristics, vegetable-oil-based
      polymers play an important role in biomaterials and have attracted increasing
      attention from the polymer community. Here we comprehensively review recent
      developments in the preparation of vegetable-oil-based polyurethane, polyester,
      polyether and polyolefin, all of which have potential applications as
      biomaterials. 

PMID- 24012609
TI  - High phosphate feeding induced arterial medial calcification in uremic rats:
      roles of Lanthanum carbonate on protecting vasculature.
AB  - AIMS: High cardiovascular mortality in patients with end-stage renal disease is
      closely associated with arterial medial calcification (AMC) caused by
      hyperphosphatemia, the mechanism of which associated hormones (FGF-23, klotho)
      and osteochondrogenic events is unclear. We examined the effect of Lanthanum
      carbonate on AMC via regulating the abnormalities in phosphorus metabolism of
      uremic rats. MAIN METHODS: 45 healthy SD rats were randomly divided into 3
      groups: Normal group (n=15), CRF group (n=15), CRF diet supplemented with 2% La
      (n=15). AMC in great arteries were evaluated by VonKossa. Osteochondrogenic
      specific genes were analyzed by Immunohistochemistry and qRT-PCR. Serum FGF-23
      and klotho levels were detected by ELISA kit. KEY FINDINGS: Serum phosphate was
      markedly increased in CRF group (6.94 +/- 0.97 mmol/L) and 2%La group (5.12 +/-
      0.84 mmol/L) at week 4, while the latter became hypophosphatemic (2.92 +/- 0.73
      mmol/L vs CRF group, p<0.01) at week 10. Inhibitory effect of 2%La on development
      of AMC was reflected by downregulated Runx2, Osterix, BSP, Osteocalcin and
      collagenII and a reduction of FGF-23 at week 4(vs CRF group, p<0.01) but not week
      10. SIGNIFICANCE: Beneficial effects of Lanthanum carbonate on progression of AMC
      in CRF could be mainly due to the decreased phosphate retention and FGF-23 in
      early stage and likewise a reduction of bone-associated proteins via
      osteochondrogenic pathway. Lanthanum carbonate has no effect on soluble klotho
      and serum FGF-23 in late stage of CRF.

PMID- 24012610
TI  - Polymorphisms and genetic linkage of histamine receptors.
AB  - Histamine is a biogenic amine that plays an essential role in controlling many
      physiological functions, both in the central nervous system (CNS) and the
      peripheral nervous system (PNS). Most of these physiological effects are mediated
      through interactions with four histamine receptor subtypes, all of which are
      members of the larger family of rhodopsin-like class A G-protein coupled
      receptors (GPCRs) (Leurs et al., 2011; Lim et al., 2009). Here, we focus on the
      genetic variations and polymorphisms localized on the genes encoding for human
      histamine receptors where it provides an up to date collection of all
      polymorphisms found on genes encoding the histamine receptor subtypes and their
      association to diseases.

PMID- 24012611
TI  - Differential role of cyclooxygenase-1 and -2 on renal vasoconstriction to alpha1
      adrenoceptor stimulation in normotensive and hypertensive rats.
AB  - AIMS: Hypertension is associated with the impairment of renal cyclooxygenase
      (COX) activity, which regulates vascular tone, salt and water balance and renin
      release. We aimed to evaluate the functional role of COX isoforms in kidneys
      isolated from spontaneously hypertensive rats (SHR) after alpha1-adrenoceptor
      (alpha1-AR) stimulation. MAIN METHODS: Male six-month-old SHR and normotensive
      Wistar-Kyoto rats (WKY) were used. The kidneys were isolated to measure perfusion
      pressure and COX-1- or COX-2-derived prostanoids in response to alpha1-AR
      activation. KEY FINDINGS: The basal perfusion pressure was higher in SHR kidneys
      compared with WKY kidneys (95 +/- 11 vs. 68 +/- 6 mmHg, P<0.05). Phenylephrine
      induced a greater vasopressor response in SHR kidneys (EC50 of 1.89 +/- 0.58
      nmol) than WKY kidneys (EC50 of 3.30 +/- 0.54 nmol, P<0.05 vs. SHR). COX-1
      inhibition decreased the alpha1-AR-induced vasoconstrictor response in WKY but
      did not affect SHR response, while COX-2 inhibition diminished the response in
      SHR. Both basal prostacyclin (PGI2) and thromboxane A2 (TxA2) values were higher
      in SHR kidney perfusates (P<0.05) and were reduced by COX-1 and COX-2 inhibitors
      in both strains. Furthermore, phenylephrine increased PGI2 through COX-2 in WKY
      and through COX-1 in SHR, but the agonist did not significantly modify TxA2 in
      both strains. SIGNIFICANCE: The data suggest that COX-1 contributes to
      vasoconstrictor effects in WKY kidneys and that COX-2 has the same effect in SHR
      kidneys. The results also suggest that basal release of COX-2-derived
      vasoconstrictor prostanoids is involved in renal vascular hypersensitivity in
      SHR.

PMID- 24012612
TI  - A novel plasmid and SonoVue formulation plus ultrasound sonication for effective
      gene delivery in nude mice.
AB  - AIMS: This study aimed to identify the effectiveness of gene therapy mediated by
      ultrasound-targeted SonoVue using the herpes simplex virus-thymidine kinase (TSV
      TK) driven by the kinase insert domain receptor (KDR) promoter (KDR-TK) for the
      treatment of ovarian carcinomas in nude mice. The optimized conditions for gene
      transfection were also explored. MAIN METHODS: In this study, we developed a
      novel technique to deliver a plasmid vector-carried gene into tumor xenografts in
      sixty nude mice. We first mixed plasmid DNA with SonoVue to form microbubbles and
      then treated the mice with ultrasound sonication to enhance plasmid gene
      transfection and expression in tumor xenografts. KEY FINDINGS: The data showed
      that injection of pBluescript-KDR-TK cDNA mixed with SonoVue into nude mice plus
      ultrasound sonication significantly (Group E) increased the transfection
      efficiency and expression of KDR-TK mRNA in tumor xenografts. The growth of tumor
      xenografts in nude mice was significantly suppressed in Group E compared to the
      other four control groups (Groups A, B, C, and D, namely, treatment with
      phosphate-buffered saline (PBS), KDR-TK+PBS, KDR-TK+SonoVue, KDR
      TK+PBS+ultrasound sonication, respectively). TUNEL staining showed that SonoVue
      plus ultrasound sonication significantly induced apoptosis and reduced
      microvessel density (MVD). SIGNIFICANCE: This study revealed that the formulation
      of plasmid with SonoVue plus ultrasound could provide efficient gene delivery
      into tumor xenografts. Increased gene expression was observed in vivo, which
      effectively reduced the tumor growth and MVD of tumor xenografts and induced
      apoptosis in tumor cells. Future clinical trials are necessary to further analyze
      the relevance of this technique.

PMID- 24012613
TI  - Analysis of the mechanisms underlying the antinociceptive effect of epicatechin
      in diabetic rats.
AB  - AIMS: The purpose of this study was to investigate the antinociceptive effect of
      epicatechin as well as the possible mechanisms of action in diabetic rats. MAIN
      METHODS: Rats were injected with streptozotocin to produce hyperglycemia. The
      formalin test was used to assess the nociceptive activity. KEY FINDINGS: Acute
      pre-treatment with epicatechin (0.03-30 mg/kg, i.p.) prevented formalin-induced
      nociception in diabetic rats. Furthermore, daily or every other day treatment for
      2 weeks with epicatechin (0.03-30 mg/kg, i.p.) also prevented formalin-induced
      nociception in diabetic rats. Acute epicatechin-induced antinociception was
      prevented by l-NAME (N(omega)-nitro-l-arginine methyl ester hydrochloride, 1
      10mg/kg, non-selective nitric oxide synthesis inhibitor), 7-nitroindazole (0.1
      1mg/kg, selective neuronal nitric oxide synthesis inhibitor), ODQ (1H-(1,2,4)
      oxadiazolo(4,2-a)quinoxalin-1-one, 0.2-2mg/kg, guanylyl cyclase inhibitor) or
      glibenclamide (1-10mg/kg, ATP-sensitive K(+) channel blocker). Moreover,
      epicatechin (3mg/kg)-induced antinociception was fully prevented by methiothepin
      (0.1-1mg/kg, serotonergic receptor antagonist), WAY-100635 (0.03-0.3mg/kg,
      selective 5-HT1A receptor antagonist) or SB-224289 (0.03-0.3mg/kg, selective 5
      HT1B receptor antagonist). In contrast, BRL-15572 (0.03-0.3mg/kg, selective 5
      HT1D receptor antagonist) only slightly prevented the antinociceptive effect of
      epicatechin. Naloxone (0.1-1mg/kg, opioid antagonist) did not modify
      epicatechin's effect. SIGNIFICANCE: Data suggest the involvement of the nitric
      oxide-cyclic GMP-K(+) channel pathway as well as activation of 5-HT1A and 5HT1B,
      and at a lesser extent, 5-HT1D, but not opioid, receptors in the antinociceptive
      effect of epicatechin in diabetic rats. Our data suggest that acute or chronic
      treatment with epicatechin may prove to be effective to treat nociceptive
      hypersensitivity in diabetic patients.

PMID- 24012608
TI  - Strategies for directing the structure and function of three-dimensional collagen
      biomaterials across length scales.
AB  - Collagen type I is a widely used natural biomaterial that has found utility in a
      variety of biological and medical applications. Its well-characterized structure
      and role as an extracellular matrix protein make it a highly relevant material
      for controlling cell function and mimicking tissue properties. Collagen type I is
      abundant in a number of tissues, and can be isolated as a purified protein. This
      review focuses on hydrogel biomaterials made by reconstituting collagen type I
      from a solubilized form, with an emphasis on in vitro studies in which collagen
      structure can be controlled. The hierarchical structure of collagen from the
      nanoscale to the macroscale is described, with an emphasis on how structure is
      related to function across scales. Methods of reconstituting collagen into
      hydrogel materials are presented, including molding of macroscopic constructs,
      creation of microscale modules and electrospinning of nanoscale fibers. The
      modification of collagen biomaterials to achieve the desired structures and
      functions is also addressed, with particular emphasis on mechanical control of
      collagen structure, creation of collagen composite materials and crosslinking of
      collagenous matrices. Biomaterials scientists have made remarkable progress in
      rationally designing collagen-based biomaterials and in applying them both to the
      study of biology and for therapeutic benefit. This broad review illustrates
      recent examples of techniques used to control collagen structure and thereby to
      direct its biological and mechanical functions. 

PMID- 24012614
TI  - Changes of HBsAg and interferon-inducible protein 10 serum levels in naive HBeAg
      negative chronic hepatitis B patients under 4-year entecavir therapy.
AB  - BACKGROUND & AIMS: Serum HBsAg levels might represent an important predictor of
      sustained off-treatment response in HBeAg-negative chronic hepatitis B (CHB). We
      evaluated the changes of HBsAg and interferon-inducible protein 10 (IP10) serum
      levels in HBeAg-negative CHB patients treated with entecavir. METHODS: 114
      patients received entecavir for a median of 4.3 years. HBsAg levels were
      determined at baseline, 6 and 12 months and every year thereafter until year-4.
      IP10 levels were measured at baseline and annually until year-4 in 76 patients.
      RESULTS: Virological remission rates were high (year-1: 94%, after year-2: 97
      98%). Compared to baseline, HBsAg levels decreased by a median of 0.03, 0.13,
      0.17, 0.22, and 0.32 log10 IU/ml at 6 months and 1, 2, 3, and 4 years,
      respectively (p<=0.001 for all comparisons). The proportions of patients with
      HBsAg decline of >=0.5 or >=1 log10 IU/ml were 9% or 6% at year-1 and 21% or 10%
      at the last visit. Median IP10 levels (pg/ml) did not change from baseline to
      year-1 or -2 (245 vs. 229 or 251), but increased at year-3 and -4 (275 and 323,
      p<0.030). HBsAg drop >=0.5 log10 was associated with baseline IP10 or IP10 >350
      pg/ml (p<=0.002). HBsAg loss occurred in 4/114 (3.5%) patients or in 1/2, 3/21,
      and 0/91 patients with baseline HBsAg <100, 100-1000 and >1000 IU/ml,
      respectively (p<0.001). CONCLUSIONS: In HBeAg-negative CHB patients, 4-year
      entecavir therapy decreases serum HBsAg levels, but the rate of decline is rather
      slow. Serum IP10 levels represent a promising predictor of HBsAg decline in this
      setting.

PMID- 24012615
TI  - AMPKalpha1 controls hepatocyte proliferation independently of energy balance by
      regulating Cyclin A2 expression.
AB  - BACKGROUND: AMP-activated protein kinase (AMPK) is an evolutionarily conserved
      sensor of cellular energy status that contributes to restoration of energy
      homeostasis by slowing down ATP-consuming pathways and activating ATP-producing
      pathways. Unexpectedly, in different systems, AMPK is also required for proper
      cell division. In the current study, we evaluated the potential effect of the
      AMPK catalytic subunit, AMPKalpha1, on hepatocyte proliferation. METHODS:
      Hepatocyte proliferation was determined in AMPKalpha1 knockout and wild-type mice
      in vivo after two thirds partial hepatectomy, and in vitro in primary hepatocyte
      cultures. The activities of metabolic and cell cycle-related signaling pathways
      were measured. RESULTS: After partial hepatectomy, hepatocytes proliferated
      rapidly, correlating with increased AMPK phosphorylation. Deletion of AMPKalpha1
      delayed liver regeneration by impacting on G1/S transition phase. The
      proliferative defect of AMPKalpha1-deficient hepatocytes was cell autonomous, and
      independent of energy balance. The priming phase, lipid droplet accumulation,
      protein anabolic responses and growth factor activation after partial hepatectomy
      occurred normally in the absence of AMPKalpha1 activity. By contrast, mRNA and
      protein expression of cyclin A2, a key driver of S phase progression, were
      compromised in the absence of AMPK activity. Importantly, AMPKalpha1 controlled
      cyclin A2 transcription mainly through the ATF/CREB element. CONCLUSIONS: Our
      study highlights a novel role for AMPKalpha1 as a positive regulator of
      hepatocyte division occurring independently of energy balance.

PMID- 24012616
TI  - The transcription factor SALL4 regulates stemness of EpCAM-positive
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Recent evidence suggests that hepatocellular carcinoma can be
      classified into certain molecular subtypes with distinct prognoses based on the
      stem/maturational status of the tumor. We investigated the transcription program
      deregulated in hepatocellular carcinomas with stem cell features. METHODS: Gene
      and protein expression profiles were obtained from 238 (analyzed by microarray),
      144 (analyzed by immunohistochemistry), and 61 (analyzed by qRT-PCR)
      hepatocellular carcinoma cases. Activation/suppression of an identified
      transcription factor was used to evaluate its role in cell lines. The
      relationship of the transcription factor and prognosis was statistically
      examined. RESULTS: The transcription factor SALL4, known to regulate stemness in
      embryonic and hematopoietic stem cells, was found to be activated in a
      hepatocellular carcinoma subtype with stem cell features. SALL4-positive
      hepatocellular carcinoma patients were associated with high values of serum alpha
      fetoprotein, high frequency of hepatitis B virus infection, and poor prognosis
      after surgery compared with SALL4-negative patients. Activation of SALL4 enhanced
      spheroid formation and invasion capacities, key characteristics of cancer stem
      cells, and up-regulated the hepatic stem cell markers KRT19, EPCAM, and CD44 in
      cell lines. Knockdown of SALL4 resulted in the down-regulation of these stem cell
      markers, together with attenuation of the invasion capacity. The SALL4 expression
      status was associated with histone deacetylase activity in cell lines, and the
      histone deacetylase inhibitor successfully suppressed proliferation of SALL4
      positive hepatocellular carcinoma cells. CONCLUSIONS: SALL4 is a valuable
      biomarker and therapeutic target for the diagnosis and treatment of
      hepatocellular carcinoma with stem cell features.

PMID- 24012617
TI  - The effects of benzofury (5-APB) on the dopamine transporter and 5-HT2-dependent
      vasoconstriction in the rat.
AB  - 5-APB, commonly marketed as 'benzofury' is a new psychoactive substance and
      erstwhile 'legal high' which has been implicated in 10 recent drug-related deaths
      in the UK. This drug was available on the internet and in 'head shops' and was
      one of the most commonly sold legal highs up until its recent UK temporary ban
      (UK Home Office). Despite its prominence, very little is known about its
      pharmacology. This study was undertaken to examine the pharmacology of 5-APB in
      vitro. We hypothesised that 5-APB would activate the dopamine and 5-HT systems
      which may underlie its putative stimulant and hallucinogenic effects.
      Autoradiographic studies showed that 5-APB displaced both [(125)I] RTI-121 and
      [(3)H] ketanserin from rat brain tissue suggesting affinity at the dopamine
      transporter and 5-HT2 receptor sites respectively. Voltammetric studies in rat
      accumbens brain slices revealed that 5-APB slowed dopamine reuptake, and at high
      concentrations caused reverse transport of dopamine. 5-APB also caused
      vasoconstriction of rat aorta, an effect antagonised by the 5-HT2A receptor
      antagonist ketanserin, and caused contraction of rat stomach fundus, which was
      reversed by the 5-HT2B receptor antagonist RS-127445. These data show that 5-APB
      interacts with the dopamine transporter and is an agonist at the 5-HT2A and 5
      HT2B receptors in the rat. Thus 5-APB's pharmacology is consistent with it having
      both stimulant and hallucinogenic properties. In addition, 5-APB's activity at
      the 5-HT2B receptor may cause cardiotoxicity. 

PMID- 24012618
TI  - The association between galactosylation of immunoglobulin G and body mass index.
AB  - OBJECTIVE: Obesity is becoming a fast-growing health problem worldwide.
      Glycosylation of proteins and their variations significantly affect protein
      structure and function, thus altering numerous physiological and
      pathophysiological cellular processes. Since plasma glycans were significantly
      associated with body mass index (BMI) in both Croatian and Chinese populations,
      the study evaluated the association between immunoglobulin G (IgG) glycome, which
      is closer to biological function, and BMI. METHOD: The study included individuals
      from two Croatian Adriatic islands, Vis and Korcula, and individuals from
      Northern Scottish Orkney Islands. A hydrophilic interaction chromatography on
      Waters BEH Glycan chromatography column was used to analyze N-glycans attached to
      IgG in plasma samples from a total of 3515 individuals. RESULTS: A small but
      significant positive correlation between BMI and the level of neutral glycans
      without galactoses was detected. After taking into account the influence of age
      and gender, correlation coefficients indicated that BMI was responsible for up to
      2.0% of variation in the level of neutral glycans without galactoses.
      Furthermore, after adjusting the effects of age and gender, the level of neutral
      glycans with two terminal galactoses was negatively associated with BMI in
      analyzed sample groups, suggesting that BMI could be responsible for up to 3.2%
      of variation in this glycan feature. CONCLUSION: Our study is the first large
      scale study to indicate the association of BMI and changes in IgG
      galactosylation. The observed loss of galactose which is associated with
      increased BMI might be related to chronic inflammation that accompanies the
      development of obesity.

PMID- 24012619
TI  - Sex determination based on amelogenin DNA by modified electrode with gold
      nanoparticle.
AB  - We have developed a simple and renewable electrochemical biosensor based on
      carbon paste electrode (CPE) for the detection of DNA synthesis and
      hybridization. CPE was modified with gold nanoparticles (AuNPs), which are
      helpful for immobilization of thiolated bioreceptors. AuNPs were characterized by
      scanning electron microscopy (SEM). Self-assembled monolayers (SAMs) of thiolated
      single-stranded DNA (SH-ssDNA) of the amelogenin gene was formed on CPE. The
      immobilization of the probe and its hybridization with the target DNA was
      optimized using different experimental conditions. The modified electrode was
      characterized by electrochemical impedance spectroscopy (EIS) and cyclic
      voltammetry (CV). The electrochemical response of ssDNA hybridization and DNA
      synthesis was measured using differential pulse voltammetry (DPV) with methylene
      blue (MB) as an electroactive indicator. The new biosensor can distinguish
      between complementary and non-complementary strands of amelogenin ssDNA. Genomic
      DNA was extracted from blood and was detected based on changes in the MB
      reduction signal. These results demonstrated that the new biosensor could be used
      for sex determination. The proposed biosensor in this study could be used for
      detection and discrimination of polymerase chain reaction (PCR) products of
      amelogenin DNA. 

PMID- 24012620
TI  - In vivo patellofemoral contact mechanics during active extension using a novel
      dynamic MRI-based methodology.
AB  - OBJECTIVES: To establish an in vivo, normative patellofemoral (PF) cartilage
      contact mechanics database acquired during voluntary muscle control using a
      novel, dynamic, magnetic resonance (MR) imaging-based, computational methodology
      and validate the contact mechanics sensitivity to the known sub-millimeter
      methodological accuracies. DESIGN: Dynamic cine phase-contrast and multi-plane
      cine (MPC) images were acquired while female subjects (n = 20, sample of
      convenience) performed an open kinetic chain (knee flexion-extension) exercise
      inside a 3-T MR scanner. Static cartilage models were created from high
      resolution three-dimensional static MR data and accurately placed in their
      dynamic pose at each time frame based on the cine-PC (CPC) data. Cartilage
      contact parameters were calculated based on the surface overlap. Statistical
      analysis was performed using paired t-test and a one-sample repeated measures
      ANOVA. The sensitivity of the contact parameters to the known errors in the PF
      kinematics was determined. RESULTS: Peak mean PF contact area was 228.7 +/- 173.6
      mm(2) at 40 degrees  knee angle. During extension, contact centroid and peak
      strain locations tracked medially on the femoral and patellar cartilage and were
      not significantly different from each other. At 25 degrees , 30 degrees , 35
      degrees , and 40 degrees  of knee extension, contact area was significantly
      different. Contact area and centroid locations were insensitive to rotational and
      translational perturbations. CONCLUSION: This study is a first step towards
      unfolding the biomechanical pathways to anterior PF pain and osteoarthritis (OA)
      using dynamic, in vivo, and accurate methodologies. The database provides crucial
      data for future studies and for validation of, or as an input to, computational
      models.

PMID- 24012621
TI  - Exclusion of patients with sequential primary total joint arthroplasties from
      arthroplasty outcome studies biases outcome estimates: a retrospective cohort
      study.
AB  - OBJECTIVE: Total joint arthroplasty (TJA) outcome studies have largely focused on
      recipients of a single primary TJA, which may bias outcome estimates. DESIGN:
      This retrospective cohort study utilized health administrative databases from
      Ontario, Canada, to assemble a cohort that received a first primary elective hip
      or knee TJA for osteoarthritis (OA) between 2002 and 2009 (index TJA).
      Characteristics of TJA recipients at their index TJA were compared for those who
      did vs did not go on to receive one or more subsequent primary, elective hip/knee
      TJAs (multiple TJAs - yes/no) over a 2-year follow-up period. Cox proportional
      hazards, censored on death, was used to examine the relationship of receipt of
      multiple TJAs (yes/no) on rates of surgical complications for the index TJA,
      controlling for confounders. RESULTS: Among 97,374 eligible patients, 19,856
      (20.4%) received a second primary elective TJA procedure within 2 years. In
      bivariate analyses, recipients of multiple primary TJAs were significantly more
      likely than single TJA recipients to be female, younger, with fewer co
      morbidities (P < 0.0001), and to experience surgical complications with the index
      surgery, including early revision (P < 0.0001). Controlling for patient
      differences, receipt of >1 primary TJAs over 2 years was independently and
      significantly associated with lower odds of having experienced a surgical
      complication following the index arthroplasty (adjusted HR 0.65, 95%CI 0.59
      0.72). CONCLUSIONS: One in five patients receiving their first elective primary
      hip or knee TJA received a second hip/knee TJA within 2 years. Our results
      indicate that exclusion of this large subsample of TJA recipients from TJA
      outcomes studies over-estimates surgical risks and may underestimate patient
      reported benefits.

PMID- 24012622
TI  - Anxiety and depressive symptoms before and after total hip and knee arthroplasty:
      a prospective multicentre study.
AB  - BACKGROUND: A subset of patients with total hip arthroplasty (THA) or total knee
      arthroplasty (TKA) has suboptimal postoperative results in terms of Patient
      Reported Outcomes (PROs), and psychological factors could contribute to these
      suboptimal results. OBJECTIVES: To examine the prevalence of anxiety and
      depressive symptoms in patients undergoing primary THA or TKA preoperatively and
      postoperatively, and the relationship between preoperative anxiety and depressive
      symptoms on PROs of THA and TKA. DESIGN: In this prospective study patients were
      measured preoperatively, and 3 and 12 months postoperatively. Patients filled in
      the Hospital Anxiety and Depression Scale, Knee injury and Osteoarthritis Outcome
      Score (KOOS) or Hip disability and Osteoarthritis Outcome Score (HOOS) and a
      satisfaction questionnaire. RESULTS: Data were obtained from 149 hip and 133 knee
      patients. The prevalence of anxiety symptoms decreased significantly from 27.9%
      to 10.8% 12 months postoperatively in hip patients, and from 20.3% to 14.8% in
      knee patients. Depressive symptoms decreased significantly from 33.6% to 12.1% 12
      months postoperatively in hip patients, and from 22.7% to 11.7% in knee patients.
      In hip and knee patients, preoperative depressive symptoms predicted smaller
      changes in different HOOS or KOOS subscales and patients were less satisfied 12
      months postoperatively. CONCLUSIONS: Preoperatively, the prevalence of anxiety
      and depressive symptoms was high. At 3 and 12 months postoperatively, the
      prevalence of anxiety and depressive symptoms was decreased in both hip and knee
      patients. However, patients with preoperative anxiety and depressive symptoms had
      worse PROs 3 and 12 months after THA and TKA and were less satisfied than
      patients without anxiety or depressive symptoms.

PMID- 24012623
TI  - A partial lesion of the substantia nigra pars compacta and retrorubral field
      decreases the harmaline-induced glutamate release in the rat cerebellum.
AB  - The aim of the present study was to examine the influence of a partial lesion of
      both the substantia nigra pars compacta (SNC) and retrorubral field (RRF) on the
      glutamatergic transmission in the cerebellum and tremor induced by harmaline in
      rats. 6-Hydroxydopamine (6-OHDA, 8 MUg/2 MUl) was injected unilaterally into the
      region of the posterior part of the SNC and RRF. Harmaline was administered in a
      dose of 30 mg/kg ip on the 8th day after the operation and the extracellular
      level of glutamate was measured by microdialysis in vivo in the cerebellar
      vermis. Harmaline induced glutamate release in the cerebellum. The lesion which
      encompassed 23-37% neurons in the anterior SNC, 52-54% in the posterior SNC and
      47-55% in the RRF did not influence the basal extracellular glutamate level but
      decreased the harmaline-induced release of this neurotransmitter. Tremor evoked
      by harmaline was also visibly inhibited by the above lesion. The results of the
      present study seem to indicate that midbrain dopaminergic neurons influence
      glutamatergic transmission in the cerebellum which may be important for
      generation of the tremor induced by harmaline.

PMID- 24012624
TI  - Choroidal metastasis secondary to prostatic adenocarcinoma: case report and
      review of literature.
AB  - Choroidal metastasis from prostate adenocarcinoma is exceedingly rare.
      Furthermore, data addressing the optimal therapeutic strategy is limited. A 62
      year-old male patient with metastatic prostate cancer was found to have a
      choroidal metastasis after complaining of decreased vision in his left eye.
      Following treatment with external beam radiotherapy, complete response in the
      choroidal metastasis was demonstrated. A literature search was undertaken to
      highlight the therapeutic options for this rare presentation. Choroidal
      metastasis secondary to adenocarcinoma of the prostate is exceedingly rare, as
      only eight cases have been reported so far. External beam radiotherapy is an
      effective therapeutic modality. 

PMID- 24012625
TI  - An unusual presentation of Hodgkin's lymphoma: ectopic testicular involvement.

PMID- 24012626
TI  - Menopausal hot flashes: mechanisms, endocrinology, treatment.
AB  - Hot flashes (HFs) are a rapid and exaggerated heat dissipation response,
      consisting of profuse sweating, peripheral vasodilation, and feelings of intense,
      internal heat. They are triggered by small elevations in core body temperature
      (Tc) acting within a greatly reduced thermoneutral zone, i.e., the Tc region
      between the upper (sweating) and lower (shivering) thresholds. This is due in
      part, but not entirely, to estrogen depletion at menopause. Elevated central
      sympathetic activation, mediated through alpha2-adrenergic receptors, is one
      factor responsible for narrowing of the thermoneutral zone. Procedures which
      reduce this activation, such as paced respiration and clonidine administration,
      ameliorate HFs as will peripheral cooling. HFs are responsible for some, but not
      all, of the sleep disturbance reported during menopause. Recent work calls into
      question the role of serotonin in HFs. This article is part of a Special Issue
      entitled 'Menopause'. 

PMID- 24012627
TI  - Changes in synaptic efficacy in rat brain slices following extremely low
      frequency magnetic field exposure at embryonic and early postnatal age.
AB  - An earlier study demonstrated changes in synaptic efficacy and seizure
      susceptibility in adult rat brain slices following extremely low-frequency
      magnetic field (ELF-MF) exposure. The developing embryonic and early postnatal
      brain may be even more sensitive to MF exposure. The aim of the present study was
      to determine the effects of a long-term ELF-MF (0.5 and 3 mT, 50 Hz) exposure on
      synaptic functions in the developing brain. Rats were treated with chronic
      exposure to MF during two critical periods of brain development, i.e. in utero
      during the second gestation week or as newborns for 7 days starting 3 days after
      birth, respectively. Excitability and plasticity of neocortical and hippocampal
      areas were tested on brain slices by analyzing extracellular evoked field
      potentials. We demonstrated that the basic excitability of hippocampal slices
      (measured as amplitude of population spikes) was increased by both types of
      treatment (fetal 0.5 mT, newborn 3 mT). Neocortical slices seemed to be
      responsive mostly to the newborn treatment, the amplitude of excitatory
      postsynaptic potentials was increased. Fetal ELF-MF exposure significantly
      inhibited the paired-pulse depression (PPD) and there was a significant decrease
      in the efficacy of LTP (long-term potentiation induction) in neocortex, but not
      in hippocampus. On the other hand, neonatal treatment had no significant effect
      on plasticity phenomena. Results demonstrated that ELF-MF has significant effects
      on basic neuronal functions and synaptic plasticity in brain slice preparations
      originating from rats exposed either in fetal or in newborn period.

PMID- 24012629
TI  - Proteomics identifies ubiquitin-proteasome targets and new roles for chromatin
      remodeling in the Arabidopsis response to phosphate starvation.
AB  - In order to identify new regulators of the phosphate (Pi) starvation signaling
      pathway in plants, we analyzed variation in the abundance of nuclear-enriched
      proteins isolated from Arabidopsis roots that depends on Pi supply. We used 2-D
      fluorescence difference gel electrophoresis and MALDI-TOF/TOF techniques for
      proteome separation, visualization and relative protein abundance quantification
      and identification. Pi-controlled proteins identified in our analysis included
      components of the chromatin remodeling, DNA replication, and mRNA splicing
      machineries. In addition, by combining Pi starvation conditions with proteasome
      inhibitor treatments, we characterized the role of the ubiquitin-proteasome
      system, a major mechanism for targeted protein degradation in eukaryotes, in the
      control of the stability of Pi-responsive proteins. Among Pi-responsive proteins,
      the histone chaperone NAP1;2 was selected for further characterization, and was
      shown to display differential nucleo-cytoplasmic accumulation in response to Pi
      deprivation. We also found that mutants affecting three members of the NAP1
      family accumulate lower Pi levels and display reduced expression of Pi starvation
      inducible genes, reflecting a potential regulatory role for these chromatin
      remodeling proteins in Pi homeostasis. BIOLOGICAL SIGNIFICANCE: In this study, we
      explore the feasibility of nuclear proteomics to identify regulatory proteins and
      ubiquitin-proteasome targets within a specific stress signaling pathway in
      plants, in our case phosphate starvation signaling in Arabidopsis. It will be of
      interest for researchers involved in the dissection of any signaling pathway in
      plants, in particular those with an interest in the ubiquitin-proteasome
      functions, and for the plant nutrition community.

PMID- 24012628
TI  - Influence of stress-induced intermediates on gonadotropin gene expression in
      gonadotrope cells.
AB  - Despite extensive investigation, a comprehensive understanding of the mechanisms
      whereby stress impacts fertility remains elusive. Since the 1930s, when Hans
      Selye popularized studying adaptations to stress (Selye, 1937), we have learned
      that compensatory mechanisms involve a complex interplay of neural and hormonal
      processes that allow various body functions to adjust to stress, in a coordinated
      manner. In terms of reproduction, the adjustment to a stressor interferes with
      integrated functioning at multiple levels of regulation--the hypothalamus,
      anterior pituitary gland, gonads, and neural centers coordinating behavior.
      Various mediators are postulated to participate in reproductive suppression.
      These include catecholamines, cytokines, prostaglandins, endogenous opioid
      peptides, and hormones of the hypothalamic-pituitary-adrenal axis. This review
      focuses on one class of mediators, the glucocorticoids, and provides our views on
      the relevance and mode of action of this inhibitory intermediate within the
      anterior pituitary gonadotrope, as a potential cellular site whereby
      glucocorticoids contribute to stress-induced reproductive suppression.

PMID- 24012630
TI  - Hypersensitivity of hypoxia grown Mycobacterium smegmatis to DNA damaging agents:
      implications of the DNA repair deficiencies in attenuation of mycobacteria.
AB  - Mycobacteria are an important group of pathogenic bacteria. We generated a series
      of DNA repair deficient strains of Mycobacterium smegmatis, a model organism, to
      understand the importance of various DNA repair proteins (UvrB, Ung, UdgB, MutY
      and Fpg) in survival of the pathogenic strains. Here, we compared tolerance of
      the M. smegmatis strains to genotoxic stress (ROS and RNI) under aerobic, hypoxic
      and recovery conditions of growth by monitoring their survival. We show an
      increased susceptibility of mycobacteria to genotoxic stress under hypoxia. UvrB
      deficiency led to high susceptibility of M. smegmatis to the DNA damaging agents.
      Ung was second in importance in strains with single deficiencies. Interestingly,
      we observed that while deficiency of UdgB had only a minor impact on the strain's
      susceptibility, its combination with Ung deficiency resulted in severe
      consequences on the strain's survival under genotoxic stress suggesting a strong
      interdependence of different DNA repair pathways in safeguarding genomic
      integrity. Our observations reinforce the possibility of targeting DNA repair
      processes in mycobacteria for therapeutic intervention during active growth and
      latency phase of the pathogen. High susceptibility of the UvrB, or the Ung/UdgB
      deficient strains to genotoxic stress may be exploited in generation of
      attenuated strains of mycobacteria. 

PMID- 24012631
TI  - Epigenetic changes in the progression of Alzheimer's disease.
AB  - The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA
      demethylation, is driven by the ten eleven translocation (TET) family of proteins
      that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether
      methylation/demethylation status is altered during the progression of Alzheimer's
      disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5
      formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA
      from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age
      matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage
      AD (LAD) subjects by immunochemistry. The results showed significantly (p < 0.05)
      increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In
      contrast, levels of 5fC and 5caC were significantly (p < 0.05) decreased in the
      HPG of PCAD and LAD subjects. Overall, the data suggest altered
      methylation/demethylation patterns in vulnerable brain regions prior to the onset
      of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.

PMID- 24012633
TI  - Helicobacter pylori infection affects mitochondrial function and DNA repair,
      thus, mediating genetic instability in gastric cells.
AB  - Helicobacter pylori infection is an important factor for the development of
      atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining
      the effects of H. pylori infection are not fully elucidated. H. pylori infection
      is known to induce genetic instability in both nuclear and mitochondrial DNA of
      gastric epithelial cells. The mutagenic effect of H. pylori infection on nuclear
      DNA is known to be a consequence, in part, of a down-regulation of expression and
      activity of major DNA repair pathways. In this study, we demonstrate that H.
      pylori infection of gastric adenocarcinoma cells causes mtDNA mutations and a
      decrease of mtDNA content. Consequently, we show a decrease of respiration
      coupled ATP turnover and respiratory capacity and accordingly a lower level and
      activity of complex I of the electron transport chain. We wanted to investigate
      if the increased mutational load in the mitochondrial genome was caused by down
      regulation of mitochondrial DNA repair pathways. We lowered the expression of APE
      1 and YB-1, which are believed to be involved in mitochondrial base excision
      repair and mismatch repair. Our results suggest that both APE-1 and YB-1 are
      involved in mtDNA repair during H. pylori infection, furthermore, the results
      demonstrate that multiple DNA repair activities are involved in protecting mtDNA
      during infection. 

PMID- 24012634
TI  - Elevated guanylate cyclase and cyclic-guanosine monophosphate-dependent protein
      kinase levels in nasal mucosae of antigen-challenged rats.
AB  - OBJECTIVE: In patients with severe allergic rhinitis, the most serious symptom is
      rhinostenosis, which is considered to be induced by a dilatation of plexus
      cavernosum. The vascular relaxing responses to chemical mediators are mainly
      mediated by the production of nitric oxide (NO). However, the exact mechanism(s)
      in nasal venoresponsiveness of allergic rhinitis is not fully understood. In the
      present study, we investigated the roles of soluble guanylate cyclase (sGC) and
      cyclic-guanosine monophosphate (c-GMP)-dependent protein kinase G (PKG) in
      venodilatation of nasal mucosae of antigen-challenged rats. METHODS: Actively
      sensitized rats were repeatedly challenged with aerosolized antigen (2,4
      dinitrophenylated Ascaris suum). Twenty-four hours after the final antigen
      challenge, nasal septum mucosa was exposed surgically and observed directly in
      vivo under a stereoscopic microscope. The sodium nitroprusside (SNP) and 8-Br
      cGMP (a PKG activator) were administered into arterial injection, and the venous
      diameters of nasal mucosa were observed. RESULTS: The intra-arterial injections
      of SNP and 8-Br-cGMP-induced venodilatation were significantly augmented in the
      nasal mucosae of repeatedly antigen-challenged rats. Furthermore, protein
      expressions of sGC and PKG were significantly increased in nasal mucosae of the
      antigen-challenged rats. CONCLUSION: The present findings suggest the idea that
      the promoted cGMP/PKG pathway may be involved in the enhanced NO-induced
      venodilatation in nasal mucosae of antigen-challenged rats.

PMID- 24012632
TI  - Impaired mitochondrial energy production and ABC transporter function-A crucial
      interconnection in dementing proteopathies of the brain.
AB  - Ageing is the main risk factor for the development of dementing neurodegenerative
      diseases (NDs) and it is accompanied by the accumulation of variations in
      mitochondrial DNA. The resulting tissue-specific alterations in ATP production
      and availability cause deteriorations of cerebral clearance mechanisms that are
      important for the removal of toxic peptides and its aggregates. ABC transporters
      were shown to be the most important exporter superfamily for toxic peptides, e.g.
      beta-amyloid and alpha-synuclein. Their activity is highly dependent on the
      availability of ATP and forms a directed energy-exporter network, linking
      decreased mitochondrial function with highly impaired ABC transporter activity
      and disease progression. In this paper, we describe a network based on
      interactions between ageing, energy metabolism, regeneration, accumulation of
      toxic peptides and the development of proteopathies of the brain with a focus on
      Alzheimer's disease (AD). Additionally, we provide new experimental evidence for
      interactions within this network in regenerative processes in AD. 

PMID- 24012635
TI  - Blockade by phosphorothioate aptamers of advanced glycation end products-induced
      damage in cultured pericytes and endothelial cells.
AB  - Advanced glycation end products (AGEs) not only inhibit DNA synthesis of retinal
      pericytes, but also elicit vascular hyperpermeability, pathological angiogenesis,
      and thrombogenic reactions by inducing vascular endothelial growth factor (VEGF)
      and plasminogen activator inhibitor-1 (PAI-1) through the interaction with the
      receptor for AGEs (RAGE), thereby being involved in the pathogenesis of diabetic
      retinopathy. In this study, we screened novel phosphorothioate-modified aptamers
      directed against AGEs (AGEs-thioaptamers) using a combinatorial chemistry in
      vitro, and examined whether these aptamers could inhibit the AGE-induced damage
      in both retinal pericytes and human umbilical vein endothelial cells (HUVECs). We
      identified 11 AGEs-thioaptamers; among them, clones #4, #7s and #9s aptamers had
      higher binding affinity to AGEs-human serum albumin (HSA) than the others.
      Surface plasmon resonance analysis revealed that KD values of #4s, #7s and #9s
      were 0.63, 0.36, and 0.57nM, respectively. Furthermore, these 3 clones dose
      dependently restored the decrease in DNA synthesis in AGE-exposed pericytes. AGEs
      significantly increased RAGE, VEGF and PAI-1 mRNA levels in HUVEC, all of which
      were completely blocked by the treatment with 20nM clone #4s aptamer. Quartz
      crystal microbalance analysis confirmed that #4s aptamer dose-dependently
      inhibited the binding of AGEs-HSA to RAGE. Our present study demonstrated that
      AGEs-thioaptamers could inhibit the harmful effects of AGEs in pericytes and
      HUVEC by suppressing the binding of AGEs to RAGE. Blockade by AGEs-thioaptamers
      of the AGEs-RAGE axis might be a novel therapeutic strategy for diabetic
      retinopathy. 

PMID- 24012636
TI  - Contributions of endothelial nitric oxide synthase, noradrenaline, and
      neuropeptide Y to local warming-induced cutaneous vasodilatation in men.
AB  - We performed a two-part study to determine the roles of endothelial nitric oxide
      synthase (eNOS) and the vasoconstrictor nerves neurotransmitters noradrenaline
      (NA) and neuropeptide Y (NPY) in the cutaneous vasodilator response to local skin
      warming. Forearm skin sites were instrumented with intradermal microdialysis
      fibres, local heaters, and laser-Doppler flow (LDF) probes. Sites were locally
      heated from 34 to 42 degrees C. LDF was expressed as cutaneous vascular
      conductance (CVC; LDF/mean arterial pressure). In Part I, we tested whether
      sympathetic noradrenergic nerves acted via eNOS. In 8 male participants,
      treatments were as follows: 1) untreated; 2) bretylium tosylate (BT), preventing
      sympathetic neurotransmitter release; 3) l-NAA to inhibit eNOS; and 4) combined
      BT+l-NAA. At treated sites, the initial peak response was markedly reduced, and
      the plateau phase response to 35min of local warming was also reduced (P<0.05),
      which was not different among those sites (P>0.05). In Part II, we tested whether
      NA and NPY were involved in the vasodilator response to local warming. In Part
      IIa, treatments were: 1) untreated; 2) propranolol and yohimbine to antagonize
      alpha- and beta-receptors; 3) l-NAA; and 4) combined propranolol, yohimbine, and
      l-NAA. In Part IIb, conditions were: 1) untreated; 2) BIBP to antagonize Y1
      receptors; 3) l-NAA; and 4) combined BIBP and l-NAA. All treatments caused a
      reduction in the initial peak and plateau responses to local skin warming
      (P<0.05). The results of Part II indicate that both NA and NPY play roles in the
      cutaneous vasodilator response and their actions are achieved via eNOS. These
      data indicate that NA and NPY are involved in the initial, rapid rise in skin
      blood flow at the onset of local skin warming. However, their vasodilator actions
      in response to local skin warming appears to be manifested through eNOS. 

PMID- 24012637
TI  - Consumers' perception of organic product characteristics. A review.
AB  - Consumer interest in organic products is growing alongside a diversification of
      the supply. In order to serve consumers actual needs and wants regarding organic
      products, those involved in the market need to be informed about consumers'
      perception of organic products. Therefore, the state of research as regards
      consumers' perception of organic product characteristics, including basic and
      additional characteristics, product labelling, product innovations and the range
      of products on the market is displayed in this contribution. A comprehensive
      literature analysis was performed uncovering not only the state of the art in the
      field including employed methodology, but also research needs. Most studies are
      published on consumers' perception of organic products' design and labelling. A
      trend towards the so called 'organic-plus' positioning can be perceived, with
      many consumers expecting an extensive orientation towards sustainability. The
      diversity of product labels features prominently in related studies. The demand
      for reliable information, as well as the low degree of awareness of many labels
      amongst consumers becomes clear in these studies. To date, few results are
      available on consumers' perception of packaging and design of organic products,
      and even fewer for consumers' perception of range design. Both consumers'
      perception of organic product innovation and valued added services are untouched
      so far. 

PMID- 24012638
TI  - Identification, characterization, and crystal structure of an aldo-keto reductase
      (AKR2E4) from the silkworm Bombyx mori.
AB  - A new member of the aldo-keto reductase (AKR) superfamily with 3-dehydroecdysone
      reductase activity was found in the silkworm Bombyx mori upon induction by the
      insecticide diazinon. The amino acid sequence showed that this enzyme belongs to
      the AKR2 family, and the protein was assigned the systematic name AKR2E4. In this
      study, recombinant AKR2E4 was expressed, purified to near homogeneity, and
      kinetically characterized. Additionally, its ternary structure in complex with
      NADP(+) and citrate was refined at 1.3A resolution to elucidate substrate binding
      and catalysis. The enzyme is a 33-kDa monomer and reduces dicarbonyl compounds
      such as isatin and 17alpha-hydroxy progesterone using NADPH as a cosubstrate. No
      NADH-dependent activity was detected. Robust activity toward the substrate
      inhibitor 3-dehydroecdysone was observed, which suggests that this enzyme plays a
      role in regulation of the important molting hormone ecdysone. This structure
      constitutes the first insect AKR structure determined. Bound NADPH is located at
      the center of the TIM- or (beta/alpha)8-barrel, and residues involved in
      catalysis are conserved.

PMID- 24012639
TI  - Downregulation of MCT1 inhibits tumor growth, metastasis and enhances
      chemotherapeutic efficacy in osteosarcoma through regulation of the NF-kappaB
      pathway.
AB  - Monocarboxylate transporter isoform 1 (MCT1) is an important member of the proton
      linked MCT family and has been reported in an array of human cancer cell lines
      and primary human tumors. MCT1 expression is associated with developing a new
      therapeutic approach for cancer. In this study, we initially showed that MCT1 is
      expressed in a variety of human osteosarcoma cell lines. Moreover, we evaluated
      the therapeutic response of targeting MCT1 using shRNA or MCT1 inhibitor.
      Inhibiting MCT1 delayed tumor growth in vitro and in vivo, including in an
      orthotopic model of osteosarcoma. Targeting MCT1 greatly enhanced the sensitivity
      of human osteosarcoma cells to the chemotherapeutic drugs adriamycin (ADM). In
      addition, we observed that MCT1 knockdown significantly suppressed the metastatic
      activity of osteosarcoma, including wound healing, invasion and migration.
      Further mechanistic studies revealed that the antitumor effects of targeting MCT1
      might be related to the NF-kappaB pathway. Immunochemistry assay showed that MCT1
      was an independent positive prognostic marker in osteosarcoma patients. In
      conclusion, our data, for the first time, demonstrate that MCT1 inhibition has
      antitumor potential which is associated with the NF-kappaB pathway, and high MCT1
      expression predicates poor overall survival in patients with osteosarcoma. 

PMID- 24012640
TI  - Blockage of a miR-21/EGFR regulatory feedback loop augments anti-EGFR therapy in
      glioblastomas.
AB  - Epidermal growth factor receptors (EGFR) expression is frequently amplified in
      human glioblastoma cells. Nimotuzumab, a monoclonal antibody (mAb) against EGFR,
      has been used globally in clinics as an anti-cancer agent. It is largely unknown
      whether the blockade of miR-21, a microRNA that is upregulated in glioma cells,
      could amplify the effects of nimotuzumab. Herein, we have demonstrated that miR
      21 directly targets von Hippel-Lindau (VHL) and peroxisome-proliferator-activated
      receptor alpha (PPARalpha) and that miR-21 regulates EGFR/AKT signaling through
      VHL/beta-catenin and the PPARalpha/AP-1 axis. Further, the expression of miR-21
      is regulated by EGFR via the activation of beta-catenin and AP-1. These data
      indicate that a feedback loop exists between miR-21 and EGFR. We also show that
      the combination of nimotuzumab and an inhibitor of miR-21 is superior to single
      agent therapy. These results clarify a novel association between miR-21 and EGFR
      in the regulation of cancer cell progression. 

PMID- 24012641
TI  - Comparative RNA-seq analysis reveals potential mechanisms mediating the
      conversion to androgen independence in an LNCaP progression cell model.
AB  - The androgen-independent phenotype is an important symptom of refractory prostate
      cancer. However, the molecular mechanisms underlying this phenotypic conversion
      remain unclear. Using RNA-seq analysis of androgen-dependent prostate cancer
      cells (LNCaP) vs. androgen-independent cancer cells (LNCaP-AI-F), we identified
      788 differentially expressed genes, 315 alternative splicing events, and eight
      novel LNCaP-AI-F-specific fusion genes. The fusion genes EIF2AK1-ATR and GLYR1
      SLC9A8 were predicted to be damaging and oncogenic. We also observed dramatic
      changes in androgen receptor (AR)-mediated pathway molecules, including prostate
      specific antigen (PSA, a major biomarker of prostate cancer) and AR variants, as
      well as neuroendocrine-like (NE-like) and tumor stem cell-like characteristics,
      during androgen-independent phenotype progression. Our findings provide new
      insights into the regulatory complexities of refractory prostate cancers. 

PMID- 24012642
TI  - Involvement of hippocampal Arc in amnesia and its recovery by alcoholic extract
      of Ashwagandha leaves.
AB  - Arc (Activity-regulated cytoskeletal-associated protein) is a member of the
      immediate-early gene (IEG) family protein. Because of its critical role in
      learning and memory, it is widely considered to be an important protein in
      synaptic plasticity and related neurobiological functions. Alcoholic extract of
      Ashwagandha leaves (i-Extract) was recently shown to have preventive and
      therapeutic potential for scopolamine-induced amnesia and glutamate-induced
      excitotoxicity. In the present study, we investigated the involvement of Arc in
      scopolamine-induced amnesia and its recovery by i-Extract with particular focus
      to the changes in Arc expression in the hippocampus and cerebral cortex of mice.
      Morris water maze test showed that spatial learning and memory of mice were
      drastically reduced by scopolamine administration but improved with i-Extract
      treatment as compared to control and scopolamine-challenged mice. Molecular
      analysis revealed a remarkable decline in Arc expression in both hippocampus and
      cerebral cortex of amnesic mice, which was recovered after i-Extract treatment.
      Interestingly, Arc expression showed better recovery in the hippocampus than the
      cerebral cortex and the pre-treatment with i-Extract was more effective than the
      post-treatment. These findings suggest that Arc may be involved in i-Extract
      mediated recovery from amnesia. 

PMID- 24012643
TI  - Antifungal, antioxidant and anti-inflammatory activities of Oenanthe crocata L.
      essential oil.
AB  - The present study reports the chemical composition, antifungal, antioxidant and
      anti-inflammatory properties as well as the cytotoxicity of Oenanthe crocata
      essential oil and one of its main compounds. The essential oil was obtained from
      the aerial parts of the plant by hydrodistillation and analysed by GC and GC/MS.
      The oil was predominantly composed of monoterpene hydrocarbons (85.8%), being the
      main compounds trans-beta-ocimene (31.3%), sabinene (29.0%) and cis-beta-ocimene
      (12.3%). For the antifungal activity, the minimal inhibitory and minimal lethal
      concentrations (MICs and MLCs) were determined. The oil was particularly active
      against dermatophytes and Cryptococcus neoformans, with MIC values ranging from
      0.08 to 0.16 MUL/mL. Regarding the anti-inflammatory activity, both the oil and
      sabinene demonstrated strong anti-inflammatory activity through nitric oxide (NO)
      production inhibition in lipopolysaccharide (LPS) plus interferon gamma (IFN
      gamma)-triggered macrophages. Furthermore, the essential oil showed a potent NO
      scavenging effect and inhibited inducible NO synthase expression. Interestingly,
      and although we detected a cytotoxic effect in macrophages and keratinocytes for
      the highest concentrations tested of the oil and sabinene, we also disclosed
      bioactive and safe concentrations to be further explored for therapeutic
      proposes. Taking together, these results support the use of the oil and sabinene
      for the management of dermatophytosis and/or inflammatory-related diseases.

PMID- 24012644
TI  - Effects of 90-day feeding of transgenic Bt rice TT51 on the reproductive system
      in male rats.
AB  - Rice is a staple food crop; however, the threat of pests leads to a serious
      decline in its output and quality. The CryAb/CryAc gene, encodes a synthetic
      fusion Bacillus thuringiensis (Bt) crystal protein, was introduced into rice
      MingHui63 to produce insect-resistant rice TT51. This study was undertaken to
      investigate potential unintended effects of TT51 on the reproductive system in
      male rats. Male rats were treated with diets containing 60% of either TT51 or
      MingHui63 by weight, nutritionally balanced to an AIN93G diet, for 90days. An
      additional negative control group of rats were fed with a rice-based AIN93G diet.
      Body weights, food intake, hematology, serum chemistry, serum hormone levels,
      sperm parameters and relative organ/body weights were measured, and gross as well
      as microscopic pathology were examined. No diet-related significant differences
      in the values of response variables were observed between rats that were fed with
      diet containing transgenic TT51, MingHui63 and the control in this 90-day feeding
      study. In addition, necropsy and histopathology examination indicated no
      treatment-related changes. The results from the present study indicated that TT51
      does not appear to exert any effect on the reproductive system in male rats
      compared with MingHui63 or the control. 

PMID- 24012645
TI  - Mice exposed to dim light at night exaggerate inflammatory responses to
      lipopolysaccharide.
AB  - The mammalian circadian system regulates many physiological functions including
      inflammatory responses. Appropriately timed light information is essential for
      maintaining circadian organization. Over the past ~120 years, urbanization and
      the widespread adoption of electric lights have dramatically altered lighting
      environments. Exposure to light at night (LAN) is pervasive in modern society and
      disrupts core circadian clock mechanisms. Because microglia are the resident
      macrophages in the brain and macrophages contain intrinsic circadian clocks, we
      hypothesized that chronic exposure to LAN would alter microglia cytokine
      expression and sickness behavior following LPS administration. Exposure to 4
      weeks of dim LAN elevated inflammatory responses in mice. Mice exposed to dimly
      lit, as compared to dark, nights exaggerated changes in body temperature and
      elevated microglia pro-inflammatory cytokine expression following LPS
      administration. Furthermore, dLAN mice had a prolonged sickness response
      following the LPS challenge. Mice exposed to dark or dimly lit nights had
      comparable sickness behavior directly following the LPS injection; however, dLAN
      mice showed greater reductions in locomotor activity, increased anorectic
      behavior, and increased weight loss than mice maintained in dark nights 24h post
      LPS injection. Overall, these data suggest that chronic exposure to even very low
      levels of light pollution may alter inflammatory responses. These results may
      have important implications for humans and other urban dwelling species that
      commonly experience nighttime light exposure.

PMID- 24012646
TI  - "Anatomy of an Illness": control from a caregiver's perspective.
AB  - Caregivers of loved ones with chronic illnesses experience an uncontrollable
      challenge with potentially negative behavioral and medical consequences.
      Extensive research has demonstrated immune and endocrine regulation can be
      significantly disrupted by negative behavioral factors based on both animal
      models and human studies. However, fewer studies have focused on how psychosocial
      interventions might reverse the negative consequences of stressors such as
      caregiving. The distress of caring for individuals with cancer has only recently
      begun to receive attention. These interventions addressing caregiver distress are
      rare overall and caregivers of patients receiving hematopoietic stem cell
      transplants (HSCT) have received even less attention. HSCT caregivers report
      feelings of loss of control. Animal studies suggest that control over aversive
      events can mitigate the negative consequences of stressors. Caregivers of
      allogeneic HSCT patients for blood cancers must be available 24/7 for three
      months or longer following stem cell infusion to closely monitor the recipients'
      health and well-being. Does establishing a greater sense of control have positive
      impacts on caregivers? A randomized control trial of a cognitive behavioral
      stress management intervention for allogeneic HSCT caregivers is briefly
      described. A model of caregiver mental health which may potentially impact the
      patient's quality of life is proposed. These relationships exist in a complex
      system that includes genetic influences, sex, social environment, and prior
      experience. This system fits well within recent formulations of a "complexity
      science" approach to health and well-being. 

PMID- 24012648
TI  - The effect of snus on alcohol-related cigarette administration in dependent and
      non-dependent smokers.
AB  - INTRODUCTION: Alcohol has been found to increase tobacco smoking in both
      dependent daily smokers (DDS) and nondependent nondaily smokers (NNS), yet little
      attention has been directed toward examining how different treatments/products
      modify drinking-related smoking behavior. METHODS: This study examined the acute
      effects of snus (4mg of nicotine) on alcohol-related smoking responses in 18 DDS
      and 17 NNS. During each double-blind session, participants were randomly assigned
      to receive one of the following combinations: alcohol and snus, alcohol and
      placebo snus, placebo alcohol and snus, or placebo alcohol and placebo snus.
      Participants consumed their assigned beverage before absorbing their session's
      product, and after 30min participants could self-administer puffs of their
      preferred brand of cigarette over a 60-minute period using a progressive ratio
      task. RESULTS: Alcohol significantly increased tobacco craving (p<.001) and
      tended to decrease latency to start smoking (p=.021) but only among NNS. In
      contrast, snus tended to decrease the number of puffs earned and how hard DDS
      worked for puffs in both beverage conditions (ps<=.019) but it did not alter the
      smoking behavior of NNS. Craving was not significantly impacted by snus in either
      type of smoker. DISCUSSION: These findings raise the possibility that different
      processes mediate alcohol and cigarette co-use in NNS and DDS and suggest that
      snus may be effective in reducing alcohol-related cigarette use in DDS
      specifically.

PMID- 24012647
TI  - Brain antigen-reactive CD4+ T cells are sufficient to support learning behavior
      in mice with limited T cell repertoire.
AB  - Numerous methods of T cell depletion lead to impairment of learning and memory
      function in mice. While adoptive transfer of whole splenocytes rescues learning
      behavior impairments, the precise sub-population and antigenic specificity of the
      T cells mediating the rescue remains unknown. Using several transgenic mouse
      models in combination with adoptive transfers, we demonstrate the necessity of an
      antigen-specific CD4(+) T cell compartment in normal spatial learning and memory,
      as measured by the Morris water maze (MWM). Moreover, transfer of a monoclonal T
      cell population reactive to the central nervous system (CNS) antigen, myelin
      oligodendrocyte glycoprotein (MOG), was sufficient to improve cognitive task
      performance in otherwise impaired OTII mice, raising the possibility that the
      antigen-specificity requirement of pro-cognitive T cells may be directed against
      CNS-derived self-antigens. 

PMID- 24012649
TI  - Suppression of lithium chloride-induced conditioned gaping (a model of nausea
      induced behaviour) in rats (using the taste reactivity test) with metoclopramide
      is enhanced by cannabidiolic acid.
AB  - We aimed to determine the potential of various doses of metoclopramide (MCP, a
      dopamine antagonist) to reduce lithium chloride (LiCl)-induced conditioned gaping
      (a nausea-induced behaviour) in rats, using the taste reactivity test. We then
      evaluated whether an ineffective low dose of cannabidiolic acid (CBDA, 0.1
      MUg/kg, Rock and Parker, 2013), the potent acidic precursor of cannabidiol (CBD,
      a non-psychoactive component of cannabis) could enhance the anti-nausea effects
      of an ineffective low dose of MCP. MCP (3.0 mg/kg) reduced conditioned gaping
      responses. Coadministration of ineffective doses of MCP (0.3 mg/kg) and CBDA (0.1
      MUg/kg) enhanced the suppression of conditioned gaping, over that of either drug
      alone, without interfering with conditioned taste avoidance. MCP dose-dependently
      reduced nausea-induced conditioned gaping in rats. As well, the suppression of
      conditioned gaping was enhanced when ineffective doses of MCP and CBDA were
      coadministered. These data suggest that CBDA could be a powerful adjunct
      treatment to anti-emetic regimens for chemotherapy-induced nausea.

PMID- 24012650
TI  - Contrast reversal of the eyes impairs infants' face processing: a near-infrared
      spectroscopic study.
AB  - Human can easily detect other's eyes and gaze from early in life. Such
      sensitivity is supported by the contrast polarity of human eyes, which have a
      white sclera contrasting with the darker colored iris (Kobayashi & Kohshima,
      (1997). Nature, 387, 767-768; Kobayashi & Kohshima, (2001). Journal of Human
      Evolution, 40, 419-435). Recent studies suggest that the contrast polarity around
      the eyes plays an important role in infants' face processing. Newborns preferred
      upright face images to inverted ones in contrast-preserved faces, but not in
      contrast-reversed faces (Farroni et al., (2005). Proceedings of National Academy
      of Sciences of the United States of America, 102, p. 17245-17250). Seven- to 8
      month-old infants failed to discriminate between faces when the contrast polarity
      of eyes was reversed (Otsuka et al., (2013). Journal of Experimental Child
      Psychology, 115, 598-606). Neuroimaging study with adults revealed that full
      negative faces induced less activation in the right fusiform gyrus than either
      full-positive faces or negative faces with contrast-preserved eyes (Gilad et al.,
      (2009). Proceedings of National Academy of Sciences of the United States of
      America, 106, p. 5353-5358). In the present study, we investigated whether
      contrast-reversed eyes diminish infants' brain activity related to face
      processing. We measured hemodynamic responses in the bilateral temporal area of 5
      to 6-month-old infants. Their hemodynamic responses to faces with positive eyes
      and those with negative eyes were compared against the baseline activation during
      the presentation of object images. We found that the presentation of faces with
      positive eyes increased the concentration of oxy-Hb in the right temporal area
      and those of total-Hb in the bilateral temporal areas. No such change occurred
      for faces with negative eyes. Our results suggest the importance of contrast
      polarity of the eyes in the face-selective neural responses from early
      development. 

PMID- 24012651
TI  - Surgical treatment for venous malformation.
AB  - Sclerotherapy is generally the preferred treatment for venous malformation (VM)
      with surgery usually playing an adjunctive role. This study presents our
      experience with surgical treatment of VMs. Consecutive patients were identified
      from our vascular anomalies database 1996-2011 and patient demographics, location
      of the lesion, type of tissue(s) affected and symptoms were analysed. The
      patients completed a questionnaire to assess the impact of surgery on the
      severity of symptoms, appearance, function and overall quality of life (QoL),
      using a visual analogue scale of 0 (no symptom) to 10 (maximal symptom). They
      also rated their overall satisfaction of treatment using a scale of 0 (complete
      dissatisfaction) to 10 (complete satisfaction). Fifty patients with VM underwent
      a total of 58 procedures. Complication occurred in six patients (9.7% of
      operations), including transient sensory loss (n=3) and permanent frontal branch
      palsy (n=1), haematoma formation (n=1) and minor wound dehiscence (n=1). At least
      50% improvement in symptoms of background pain, acute episodic pain, contour
      deformity and skin discolouration occurred in 88.9%, 92.3%, 83.3% and 75.0% of
      patients, respectively. At least 50% improvement in the appearance, function and
      overall QoL occurred in 54.3%, 71.4% and 70.4% of patients, respectively. The
      mean overall patient satisfaction with the treatment was 8.9 (range, 1-10).
      Surgery remains an important treatment modality for selected patients with VM
      having low complication rates and high patient satisfaction. It improves the
      appearance, function and overall QoL for the majority of the patients by reducing
      the severity of pain, contour deformity and skin discolouration.

PMID- 24012652
TI  - Prevalence of vitamin D deficiency and consequences for PTH reference values.
AB  - Reference values of PTH depend on vitamin D status of the reference population.
      This is often not described in package inserts. The aim of the present study was
      therefore to calculate assay specific PTH reference levels in EDTA plasma for the
      Architect (Abbott) in relation to 25-hydroxyvitamin D (25OHD) levels. The
      relation between PTH levels, 25OHD, BMI, age, gender and kidney function was
      determined in a cohort of older individuals from the Longitudinal Aging Study
      Amsterdam (LASA, n = 738, age 55-65 years) and in a cohort of healthy individuals
      from the Netherlands Study of Depression and Anxiety (NESDA, n = 633, 18-65
      years). The LASA cohort is a representative sample of the Dutch older population.
      As expected, PTH reference values were significantly lower in 25OHD sufficient
      subjects (25OHD>50 nmol/L) than in 25OHD deficient and insufficient subjects. The
      97.5th percentile of PTH in 25OHD sufficient subjects was 10 pmol/L (94.3 pg/mL),
      which was higher than the upper limit stated by the manufacturer (7.2 pmol/L or
      68.3 pg/mL). The relation between vitamin D and PTH was independent of age,
      gender, BMI and kidney function. In conclusion, we have shown that it is
      important to establish PTH reference values in a local reference population
      taking 25OHD status into account.

PMID- 24012653
TI  - Quality indicators to detect pre-analytical errors in laboratory testing.
AB  - The identification of reliable quality indicators (QIs) is a crucial step in
      enabling users to quantify the quality of laboratory services. The current lack
      of attention to extra-laboratory factors is in stark contrast to the body of
      evidence pointing to the multitude of errors that continue to occur, particularly
      in the pre-analytical phase. The ISO 15189: 2012 standard for laboratory
      accreditation defines the pre-analytical phase, and recognizes the need to
      evaluate, monitor and improve all the procedures and processes in the initial
      phase of the testing cycle, including those performed in the phase of requesting
      tests and collecting samples, the so-called "pre-pre-analytical phase".
      Therefore, QIs should allow the identification of errors and non-conformities
      that can occur in all steps of the pre-analytical phase. Traditionally, pre
      analytical errors are grouped into identification and sample problems. However,
      appropriate test requesting and complete request forms are now recognized as
      fundamental components in providing valuable laboratory services. The model of
      QIs developed by the Working Group of the International Federation of Clinical
      Chemistry and Laboratory Medicine (IFCC) includes indicators related to both
      identification and sample problems as well as all other pre-analytical defects,
      including those in test requesting and request forms. It, moreover, provides the
      framework (with objective criteria) necessary for promoting the harmonization of
      available QIs in the pre-analytical phase.

PMID- 24012654
TI  - Endoscopic surgery of the posterior fossa: strengths and limitations.

PMID- 24012655
TI  - Is there a role for decompressive craniectomy in children after stroke?

PMID- 24012656
TI  - Resting state functional connectivity: its physiological basis and application in
      neuropharmacology.
AB  - Brain structures do not work in isolation; they work in concert to produce
      sensory perception, motivation and behavior. Systems-level network activity can
      be investigated by resting state magnetic resonance imaging (rsMRI), an emerging
      neuroimaging technique that assesses the synchrony of the brain's ongoing
      spontaneous activity. Converging evidence reveals that rsMRI is able to
      consistently identify distinct spatiotemporal patterns of large-scale brain
      networks. Dysregulation within and between these networks has been implicated in
      a number of neurodegenerative and neuropsychiatric disorders, including
      Alzheimer's disease and drug addiction. Despite wide application of this approach
      in systems neuroscience, the physiological basis of these fluctuations remains
      incompletely understood. Here we review physiological studies in electrical,
      metabolic and hemodynamic fluctuations that are most pertinent to the rsMRI
      signal. We also review recent applications to neuropharmacology - specifically
      drug effects on resting state fluctuations. We speculate that the mechanisms
      governing spontaneous fluctuations in regional oxygenation availability likely
      give rise to the observed rsMRI signal. We conclude by identifying several open
      questions surrounding this technique. This article is part of the Special Issue
      Section entitled 'Neuroimaging in Neuropharmacology'. 

PMID- 24012657
TI  - Acetyl-L-carnitine rescues scopolamine-induced memory deficits by restoring
      insulin-like growth factor II via decreasing p53 oxidation.
AB  - Alzheimer's disease (AD) is characterized by the cholinergic neurons loss and
      impairments of learning and memory. Scopolamine is common used to imitate AD
      pathological features and also causes an obvious oxidative stress. In this study,
      we found that intraperitoneal administration of supplementary acetyl-L-carnitine
      partially reverses the learning and memory defects induced by scopolamine. We
      also found that acetyl-L-carnitine reverses the impairment of long-term
      potentiation, dendritic abnormalities, and the impaired recruitment of synaptic
      protein. The beneficial effects of acetyl-L-carnitine may occur through
      amelioration of oxidative stress because it effectively decreases the levels of
      oxidative products and increases the activity of superoxide dismutase; this leads
      to a recovery in the suppressed activity of p53 caused oxidative stimuli, which
      in turn restores levels of insulin-like growth factor II, an important hormone
      for learning and memory. Our study provides the first evidence of the potential
      utility of acetyl-L-carnitine in treating the synaptic disorders prevalent in AD
      and other neurodegenerative diseases. This article is part of the Special Issue
      entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

PMID- 24012658
TI  - Effects of the hallucinogen 2,5-dimethoxy-4-iodophenethylamine (2C-I) and
      superpotent N-benzyl derivatives on the head twitch response.
AB  - N-benzyl substitution markedly enhances the affinity of phenethylamine
      hallucinogens at the 5-HT(2A) receptor. N-benzyl substituted derivatives of 2,5
      dimethoxy-4-iodophenethylamine (2C-I), such as N-(2-methoxybenzyl)-2,5-dimethoxy
      4-iodophenethylamine (25I-NBOMe) and N-(2,3-methylenedioxybenzyl)-2,5-dimethoxy-4
      iodophenethylamine (25I-NBMD), have appeared recently as designer drugs, but have
      not been characterized behaviorally. The head twitch response (HTR) is induced by
      5-HT(2A) receptor activation in rats and mice, and is widely used as a behavioral
      proxy for hallucinogen effects in humans. Nevertheless, it is not clear whether
      phenethylamine hallucinogens reliably provoke this behavior. Hence, we
      investigated whether 2C-I, 25I-NBOMe and 25I-NBMD induce head twitches in
      C57BL/6J mice. The HTR was assessed using a head-mounted magnet and a
      magnetometer coil. 2C-I (1-10 mg/kg SC), 25I-NBOMe (0.1-1 mg/kg SC), and 25I-NBMD
      (1-10 mg/kg SC) induced the HTR. 25I-NBOMe displayed 14-fold higher potency than
      2C-I, and the selective 5-HT(2A) antagonist M100,907 completely blocked the HTR
      induced by all three compounds. These findings show that phenethylamine
      hallucinogens induce the HTR by activating 5-HT(2A) receptors. Our results
      demonstrate that 25I-NBOMe is a highly potent derivative of 2C-I, confirming
      previous in vitro findings that N-benzyl substitution increases 5-HT(2A)
      affinity. Given the high potency and ease of synthesis of N
      benzylphenethylamines, it is likely that the recreational use of these
      hallucinogens will become more widespread in the future.

PMID- 24012659
TI  - beta-Adrenergic system, a backstage manipulator regulating tumour progression and
      drug target in cancer therapy.
AB  - beta-Adrenoceptors are broadly distributed in various tissues of the body. Stress
      hormones regulate a panel of important physiological functions and disease states
      including cancer. Nicotine and its derivatives could stimulate the release of
      stress hormones from cancer cells, leading to the promotion of cancer
      development. beta-Blockers have been widely used to control hypertension for
      decades. Recently, these agents could have significant implications in cancer
      therapy through blockade of adrenoceptors in tumour tissues. In this review, we
      summarize recent advancements about the influence of stress hormones, nicotine
      and beta-adrenoceptors on cancer cell proliferation, apoptosis, invasion and
      metastasis, and also tumour vasculature normalization. Relevant signal pathways
      and potential value of beta-blockers in the treatment of cancer are also
      discussed in this review. 

PMID- 24012660
TI  - Autophagy contributes to modulating the cytotoxicities of Bcl-2 homology domain-3
      mimetics.
AB  - The dysregulation of apoptosis is a key step in developing cancers, and mediates
      resistance to cancer therapy. Commitment to apoptosis is caused by
      permeabilization of the outer mitochondrial membrane, a process regulated by the
      interactions between different proteins of Bcl-2 family. Furthermore, Bcl-2
      family proteins also bind to the endoplasmic reticulum, where they modulate
      autophagy, another important pathway regulating cell survival and death.
      Dysregulation of Bcl-2 family has been demonstrated in a wide spectrum of human
      cancers, including gastrointestinal cancers. Therefore, targeting the Bcl-2
      family of proteins represents a promising therapeutic approach for these
      malignancies. Recent advances have yielded small molecules that have close
      structural or functional similarity to BH3-only proteins and are therefore named
      BH3 mimetics. Of these BH3 mimetics, obatoclax, (-)-gossypol, and ABT-263 are
      currently in clinical trials for multiple cancers. Growing evidence indicates
      that these BH3 mimetics not only induce apoptosis, but also regulate autophagy
      which may serve as a pro-survival or pro-death mechanism to counteract or mediate
      the cytotoxicity of BH3 mimetics. This review discusses the role of autophagy in
      cell-fate decision upon BH3 mimetics treatment. Further exploration of our
      understanding of the association between autophagy and cellular outcomes in
      response to BH3 mimetics treatment will likely offer improved therapies for
      patients with cancer. 

PMID- 24012661
TI  - Tumor and its microenvironment: a synergistic interplay.
AB  - The mutual and interdependent interaction between tumor and its microenvironment
      is a crucial topic in cancer research. Recently, it was reported that targeting
      stromal events could improve efficacies of current therapeutics and prevent
      metastatic spreading. Tumor microenvironment is a "complex network" of different
      cell types, soluble factors, signaling molecules and extracellular matrix
      components, which orchestrate the fate of tumor progression. As by definition,
      cancer stem cells (CSCs) are proposed to be the unique cell type able to maintain
      tumor mass and survive outside the primary tumor at metastatic sites. Being
      exposed to environmental stressors, including reactive oxygen species (ROS), CSCs
      have developed a GSH-dependent antioxidant system to improve ROS defense
      capability and acquire a malignant phenotype. Nevertheless, tumor progression is
      dependent on extracellular matrix remodeling, fibroblasts and macrophages
      activation in response to oxidative stress, as well as epithelial mesenchymal
      transition (EMT)-inducing signals and endothelial and perivascular cells
      recruitment. Besides providing a survival advantage by inducing de novo
      angiogenesis, tumor-associated vessels contribute to successful dissemination by
      facilitating tumor cells entry into the circulatory system and driving the
      formation of pre-metastatic niche. In this review, we focus on the synergistic
      effect of hypoxia inducible factors (HIFs) and vascular endothelial growth
      factors (VEGFs) in the successful outgrowth of metastasis, integrating therefore
      many of the emerging models and theories in the field. 

PMID- 24012662
TI  - Gold nanoparticles coated polystyrene/reduced graphite oxide microspheres with
      improved dispersibility and electrical conductivity for dopamine detection.
AB  - Gold nanoparticles coated polystyrene/reduced graphite oxide (AuNPs@PS/RGO)
      microspheres have been successfully prepared via a facile process, and the
      decorative gold nanoparticles could prevent the aggregation of RGO by
      electrostatic repulsive interaction, and lead to high dispersibility of the
      composite. The prepared composite has a highly increased conductivity of 129Sm(
      1) due to the unique electrical properties of citrate reduced gold nanoparticles.
      Being employed as an electrochemical sensor for detection of dopamine, the
      modified electrode exhibits remarkable sensitivity (3.44MUA/MUM) and lower
      detection limit (5nM), with linear response in a range of 0.05-20MUM. Moreover,
      valid response to dopamine obtained in present work also indicates the
      prospective performances of AuNPs@PS/RGO microspheres to other biological
      molecules, such as nucleic acids, proteins and enzymes. 

PMID- 24012663
TI  - Enzymatic activity regulated by a surfactant and hydroxypropyl beta-cyclodextrin.
AB  - Circular dichroism spectra reveal that sodium dodecyl benzene sulfonate (SDBS) at
      low concentrations can effectively prevent the aggregation of lysozyme molecules,
      while SDBS at high concentrations can lead to conformational and structural
      change of the protein. SDBS is able to inhibit the enzymatic activity of lysozyme
      in a highly efficient dose-dependent manner. The interaction mechanism of SDBS
      with lysozyme has been investigated by measuring optical spectra. Based on
      fluorescence and UV-vis spectra, microenvironmental change in and around the
      active site region induced by SDBS has been revealed and explained. Two
      dimensional FTIR spectra have been analyzed to identify the secondary structures
      and residues of lysozyme, which have a preferential interaction with SDBS.
      Hydroxypropyl beta-cyclodextrin (HP-beta-CD) was used to detach SDBS from the
      inactivated enzyme, and complete recovery of enzymatic activity was achieved.
      Thus, the enzymatic activity of lysozyme can be regulated by SDBS and HP-beta-CD.

PMID- 24012664
TI  - Design and evaluation of mixed self-assembled monolayers for a potential use in
      everolimus eluting coronary stents.
AB  - Coronary artery disease (CAD) is still the leading cause of death throughout the
      world. Metal stents are used to widen narrowed arteries. In addition, drug
      eluting stents (DES) are widely implanted to decrease the risk of in-stent
      restenosis. Commercially available polymer-based DES suffer from some
      limitations. To avoid these drawbacks, the use of self-assembled monolayers
      (SAMs) in DES has recently been investigated. In this study, methyl- and carboxyl
      terminated mixed SAMs on gold (Au) surfaces were successfully prepared. The
      samples were characterized using scanning electron microscopy (SEM), X-ray
      photoelectron spectroscopy (XPS), atomic force microscopy (AFM), Fourier
      transform infrared spectroscopy (FTIR), and contact angle goniometry (CA). The
      mixed SAM-coated surfaces were evaluated for everolimus delivery. The drug
      release in PBS was studied using high performance liquid chromatography (HPLC)
      and quartz crystal nanobalance (QCN). The results were compared with those
      related to homogenous SAM-coated surfaces. Significant differences (p<0.05) were
      found in the amount of drug eluted between the mixed SAM and the homogenous one.
      The findings are promising for the application of mixed SAMs in DES. 

PMID- 24012665
TI  - Self nanoemulsifying drug delivery system (SNEDDS) of rosuvastatin calcium:
      design, formulation, bioavailability and pharmacokinetic evaluation.
AB  - The aim of the present study is to improve solubility and bioavailability of
      Rosuvastatin calcium using self nanoemulsifying drug delivery system (SNEDDS).
      Self emulsifying property of various oils including essential oils was evaluated
      with suitable surfactants and co-surfactants. Ternary phase diagrams were
      constructed based on Rosuvastatin calcium solubility analysis for optimizing the
      system. The prepared formulations were evaluated for self emulsifying time,
      robustness to dilution, droplet size determination and zeta potential analysis.
      The system was found to be robust in different pH media and dilution volume. The
      globule size of the optimized system was less than 200nm which could be an
      acceptable nanoemulsion size range. The zeta potential of the selected CN 7
      SNEDDS formulation (cinnamon oil 30%; labrasol 60%; Capmul MCM C8 10%) was 
      29.5+/-0.63 with an average particle size distribution of 122nm. In vitro drug
      release studies showed remarkable increase in dissolution of CN7 SNEDDS compared
      to marketed formulation. In house developed HPLC method for determination of
      Rosuvastatin calcium in rat plasma was used in the bioavailability and
      pharmacokinetic evaluation. The relative bioavailability of self nanoemulsified
      formulation showed an enhanced bioavailability of 2.45 times greater than that of
      drug in suspension. The obtained plasma drug concentration data was processed
      with PKSolver 2.0 and it was best fit into the one compartment model. 

PMID- 24012666
TI  - Resistin levels are related to fat mass, but not to body mass index in children.
AB  - The relationship of resistin levels with obesity remains unclear. The aim of this
      study was to determine resistin levels in prepubertal children and adolescents
      and evaluate their association with anthropometric parameters and body
      composition. The study population included 420 randomly selected 6-8-year-old
      children and 712 children aged 12-16 years. Anthropometric data were measured and
      body mass index (BMI) and waist-to-hip and waist-to-height ratios were
      calculated. Body composition was assessed using an impedance body composition
      analyzer. Serum resistin levels were determined using a multiplexed bead
      immunoassay. Resistin levels were not significantly different between sexes. No
      significant differences in serum resistin concentrations were found between
      obese, overweight, and normal weight children at any age, and no significant
      correlations were observed between resistin concentrations and weight or BMI.
      However, resistin levels showed a significant positive correlation with fat mass
      in 12-16-year-old children, particularly in girls. In addition to describing
      serum resistin levels in prepubertal children and adolescents, our study suggests
      that resistin is related to body fat rather than to BMI in adolescents. 

PMID- 24012667
TI  - Impaired effect of relaxin on vasoconstrictor reactivity in spontaneous
      hypertensive rats.
AB  - Relaxin is thought to be involved in vasodilation to pregnancy by increasing
      endothelium-dependent vasodilation and compliance, and decreasing myogenic
      reactivity. Primary (essential) hypertension predisposes to circulatory
      maladaptation and subsequent gestational hypertensive disease. This study aimed
      to determine that vascular responses to chronic exposure to relaxin are impaired
      in young female rats with primary hypertension. In 10-12 weeks old Wistar
      Hannover rats (WHR) and spontaneous hypertensive rats (SHR), we determined
      vascular responses in isolated kidney and mesenteric arteries after 5-days of
      chronic exposure to relaxin (4 MUg/h) or placebo. SHR show decreased sensitivity
      to phenylephrine (by 67%, p<0.01) and renal perfusion flow (RPFF, by 19%,
      p<0.01), but no changes in flow-mediated vasodilation, myogenic reactivity or
      vascular compliance. In WHR, relaxin stimulated flow-mediated vasodilation (2.67
      fold, from 48 +/- 9 to 18 +/- 4 MUl/min, p = 0.001), inhibited myogenic
      reactivity (from -1 +/- 2 to 7 +/- 3 MUm/10 mmHg, p = 0.01), and decreased
      sensitivity to phenylephrine (28%, from 1.39 +/- 0.08 to 1.78 +/- 0.10 MUM,
      p<0.01), but left compliance and RPFF unchanged. NO-blockade by L-NAME diminished
      most relaxin-mediated responses. In SHR, the vasodilator effects of relaxin were
      blunted for myogenic reactivity and sensitivity to phenylephrine, with similar
      effects on flow-mediated vasodilation, compliance, RPFF and equal Rxfp1 (relaxin
      family peptide receptor) gene expression, as compared to WHR. Primary
      hypertension blunts both the relaxin-induced inhibition of myogenic reactivity
      and alpha-adrenergic vasoconstrictor response, independent from Rxfp1 gene
      expression, while the relaxin-dependent enhanced flow-mediated vasodilation
      remains intact. This implies selective resistance to relaxin in young subjects
      suffering from primary hypertension.

PMID- 24012668
TI  - Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA
      receptor trafficking.
AB  - Recent studies demonstrated that the antihypertensive drug Valsartan improved
      spatial and episodic memory in mouse models of Alzheimer's Disease (AD) and human
      subjects with hypertension. However, the molecular mechanism by which Valsartan
      can regulate cognitive function is still unknown. Here, we investigated the
      effect of Valsartan on dendritic spine formation in primary hippocampal neurons,
      which is correlated with learning and memory. Interestingly, we found that
      Valsartan promotes spinogenesis in developing and mature neurons. In addition, we
      found that Valsartan increases the puncta number of PSD-95 and trends toward an
      increase in the puncta number of synaptophysin. Moreover, Valsartan increased the
      cell surface levels of AMPA receptors and selectively altered the levels of
      spinogenesis-related proteins, including CaMKIIalpha and phospho-CDK5. These data
      suggest that Valsartan may promote spinogenesis by enhancing AMPA receptor
      trafficking and synaptic plasticity signaling.

PMID- 24012669
TI  - Characterization of early transient accumulation of PrP(Sc) in immune cells.
AB  - PrP(Sc) is known to elicit no specific immune response and the immune cells are
      suspected to support its accumulation. In the present study, we investigated the
      response of some immune cell types to PrP(Sc) to characterize an observed early
      transient accumulation of PrP(Sc). After cells were treated with PrP(Sc)-brain
      homogenate, PrP(Sc) was transiently accumulated for the first 8-12h post-exposure
      then completely cleared by the 5th day of the experiment. The accumulated PrP(Sc)
      was not a de novo product of the cell PrP(C). Further investigation of this
      phenomenon revealed some potential factors influencing it. These factors included
      cholesterol homeostasis, temperature, the degradation power of the cell and the
      availability of sufficient PrP(C). Our in vitro results suggest that immune
      cells, especially macrophages are potential risk factors for the accumulation and
      intercellular spread of PrP(Sc) if the complete clearance of PrP(Sc) were not
      fulfilled. 

PMID- 24012670
TI  - Calumenin has a role in the alleviation of ER stress in neonatal rat
      cardiomyocytes.
AB  - Disturbance of endoplasmic reticulum (ER) homeostasis causes ER stress (ERS), and
      triggers the unfolded protein response (UPR) that consequently reduces
      accumulation of unfolded proteins by increasing the quantity of ER chaperones.
      Calumenin, a Ca(2+)-binding protein with multiple EF hand motifs, which is
      located in the ER/SR, is highly expressed during the early developmental stage of
      the heart, similar to other ER-resident chaperones. The aim of this study was to
      investigate the functional role of calumenin during ERS in the heart. Like other
      chaperones (e.g., GRP94 and GRP78), calumenin expression was highly upregulated
      during ERS induced by 10 MUg/ml tunicamycin, but attenuated in the presence of
      500 MUM PBA, the chemical chaperone in neonatal rat ventricular cardiomyocytes
      (NRVCs). Upon 7.5-fold overexpression of calumenin using a recombinant adenovirus
      system, the expression levels of ERS markers (GRP78, p-PERK, and p-elF2alpha) and
      ER-initiated apoptosis markers (CHOP and p-JNK) were reduced, whereas the
      survival protein BCL-2 was upregulated during ERS compared to the control.
      Evaluation of cell viability by TUNEL assay showed that apoptosis was also
      significantly reduced by calumenin overexpression in ERS-induced cells. Taken
      together, our results suggest that calumenin plays an essential role in the
      alleviation of ERS in neonatal rat cardiomyocytes.

PMID- 24012671
TI  - Fibrillar seeds alleviate amyloid-beta cytotoxicity by omitting formation of
      higher-molecular-weight oligomers.
AB  - Amyloid-beta (Abeta) peptides can exist in distinct forms including monomers,
      oligomers and fibrils, consisting of increased numbers of monomeric units. Among
      these, Abeta oligomers are implicated as the primary toxic species as pointed by
      multiple lines of evidence. It has been suggested that toxicity could be rendered
      by the soluble higher-molecular-weight (high-n) Abeta oligomers. Yet, the most
      culpable form in the pathogenesis of Alzheimer's disease (AD) remains elusive.
      Moreover, the potential interaction among the insoluble fibrils that have been
      excluded from the responsible aggregates in AD development, Abeta monomers and
      high-n oligomers is undetermined. Here, we report that insoluble Abeta fibrillar
      seeds can interact with Abeta monomers at the stoichiometry of 1:2 (namely, each
      Abeta molecule of seed can bind to two Abeta monomers at a time) facilitating the
      fibrillization by omitting the otherwise mandatory formation of the toxic high-n
      oligomers during the fibril maturation. As a result, the addition of exogenous
      Abeta fibrillar seeds is seen to rescue neuronal cells from Abeta cytotoxicity
      presumably exerted by high-n oligomers, suggesting an unexpected protective role
      of Abeta fibrillar seeds. 

PMID- 24012672
TI  - Aronia melanocarpa and its components demonstrate antiviral activity against
      influenza viruses.
AB  - The influenza virus is highly contagious in human populations around the world
      and results in approximately 250,000-500,000 deaths annually. Vaccines and
      antiviral drugs are commonly used to protect susceptible individuals. However,
      the antigenic mismatch of vaccines and the emergence of resistant strains against
      the currently available antiviral drugs have generated an urgent necessity to
      develop a novel broad-spectrum anti-influenza agent. Here we report that Aronia
      melanocarpa (black chokeberry, Aronia), the fruit of a perennial shrub species
      that contains several polyphenolic constituents, possesses in vitro and in vivo
      efficacy against different subtypes of influenza viruses including an oseltamivir
      resistant strain. These anti-influenza properties of Aronia were attributed to
      two constituents, ellagic acid and myricetin. In an in vivo therapeutic mouse
      model, Aronia, ellagic acid, and myricetin protected mice against lethal
      challenge. Based on these results, we suggest that Aronia is a valuable source
      for antiviral agents and that ellagic acid and myricetin have potential as
      influenza therapeutics. 

PMID- 24012673
TI  - Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic
      sensitization of radioresistant A549 cells via reactive oxygen species-dependent
      p53 activation.
AB  - Biomarkers based on functional signaling have the potential to provide greater
      insight into the pathogenesis of cancer and may offer additional targets for
      anticancer therapeutics. Here, we identified hepatoma-derived growth factor
      related protein-3 (HRP-3) as a radioresistance-related gene and characterized the
      molecular mechanism by which its encoded protein regulates the radio- and
      chemoresistant phenotype of lung cancer-derived A549 cells. Knockdown of HRP-3
      promoted apoptosis of A549 cells and potentiated the apoptosis-inducing action of
      radio- and chemotherapy. This increase in apoptosis was associated with a
      substantial generation of reactive oxygen species (ROS) that was attributable to
      inhibition of the Nrf2/HO-1 antioxidant pathway and resulted in enhanced ROS
      dependent p53 activation and p53-dependent expression of PUMA (p53 upregulated
      modulator of apoptosis). Therefore, the HRP-3/Nrf2/HO-1/ROS/p53/PUMA cascade is
      an essential feature of the A549 cell phenotype and a potential radiotherapy
      target, extending the range of targets in multimodal therapies against lung
      cancer. 

PMID- 24012674
TI  - The crystal structure of human protein alpha1M reveals a chromophore-binding site
      and two putative protein-protein interfaces.
AB  - Lipocalin alpha1-microglobulin (alpha1M) is a conserved glycoprotein present in
      plasma and in the interstitial fluids of all tissues. alpha1M is linked to a
      heterogeneous yellow-brown chromophore of unknown structure, and interacts with
      several target proteins, including alpha1-inhibitor-3, fibronectin, prothrombin
      and albumin. To date, there is little knowledge about the interaction sites
      between alpha1M and its partners. Here, we report the crystal structure of the
      human alpha1M. Due to the crystallization occurring in a low ionic strength
      solution, the unidentified chromophore with heavy electron density is observed at
      a hydrophobic inner tube of alpha1M. In addition, two conserved surface regions
      of alpha1M are proposed as putative protein-protein interface sites. Further
      study is needed to unravel the detailed information about the interaction between
      alpha1M and its partners. 

PMID- 24012675
TI  - Structure of native oligomeric Sprouty2 by electron microscopy and its property
      of electroconductivity.
AB  - Receptor tyrosine kinases (RTKs) regulate many cellular processes, and Sprouty2
      (Spry2) is known as an important regulator of RTK signaling pathways. Therefore,
      it is worth investigating the properties of Spry2 in more detail. In this study,
      we found that Spry2 is able to self-assemble into oligomers with a high-affinity
      KD value of approximately 16nM, as determined through BIAcore surface plasmon
      resonance analysis. The three-dimensional (3D) structure of Spry2 was resolved
      using an electron microscopy (EM) single-particle reconstruction approach, which
      revealed that Spry2 is donut-shaped with two lip-cover domains. Furthermore, the
      method of energy dispersive spectrum obtained through EM was analyzed to
      determine the elements carried by Spry2, and the results demonstrated that Spry2
      is a silicon- and iron-containing protein. The silicon may contribute to the
      electroconductivity of Spry2, and this property exhibits a concentration
      dependent feature. This study provides the first report of a silicon- and iron
      containing protein, and its 3D structure may allow us (1) to study the potential
      mechanism through the signal transduction is controlled by switching the
      electronic transfer on or off and (2) to develop a new type of conductor or even
      semiconductor using biological or half-biological hybrid materials in the future.

PMID- 24012676
TI  - Cytoplasmic localization of Hug1p, a negative regulator of the MEC1 pathway,
      coincides with the compartmentalization of Rnr2p-Rnr4p.
AB  - The evolutionarily conserved MEC1 checkpoint pathway mediates cell cycle arrest
      and induction of genes including the RNR (Ribonucleotide reductase) genes and
      HUG1 (Hydroxyurea, ultraviolet, and gamma radiation) in response to DNA damage
      and replication arrest. Rnr complex activity is in part controlled by cytoplasmic
      localization of the Rnr2p-Rnr4p subunits and inactivation of negative regulators
      Sml1p and Dif1p upon DNA damage and hydroxyurea (HU) treatment. We previously
      showed that a deletion of HUG1 rescues lethality of mec1Delta and suppresses
      dun1Delta strains. In this study, multiple approaches demonstrate the regulatory
      response of Hug1p to DNA damage and HU treatment and support its role as a
      negative effector of the MEC1 pathway. Consistent with our hypothesis, wild-type
      cells are sensitive to DNA damage and HU when HUG1 is overexpressed. A Hug1
      polyclonal antiserum reveals that HUG1 encodes a protein in budding yeast and its
      MEC1-dependent expression is delayed compared to the rapid induction of Rnr3p in
      response to HU treatment. Cell biology and subcellular fractionation experiments
      show localization of Hug1p-GFP to the cytoplasm upon HU treatment. The
      cytoplasmic localization of Hug1p-GFP is dependent on MEC1 pathway genes and
      coincides with the cytoplasmic localization of Rnr2p-Rnr4p. Taken together, the
      genetic interactions, gene expression, and localization studies support a novel
      role for Hug1p as a negative regulator of the MEC1 checkpoint response through
      its compartmentalization with Rnr2p-Rnr4p.

PMID- 24012677
TI  - Activated alveolar epithelial cells initiate fibrosis through secretion of
      mesenchymal proteins.
AB  - Fibrosis is characterized by accumulation of activated fibroblasts and
      pathological deposition of fibrillar collagens. Activated fibroblasts overexpress
      matrix proteins and release factors that promote further recruitment of activated
      fibroblasts, leading to progressive fibrosis. The contribution of epithelial
      cells to this process remains unknown. Epithelium-directed injury may lead to
      activation of epithelial cells with phenotypes and functions similar to activated
      fibroblasts. Prior reports that used a reporter gene fate-mapping strategy are
      limited in their ability to investigate the functional significance of epithelial
      cell-derived mesenchymal proteins during fibrogenesis. We found that lung
      epithelial cell-derived collagen I activates fibroblast collagen receptor
      discoidin domain receptor-2, contributes significantly to fibrogenesis, and
      promotes resolution of lung inflammation. Alveolar epithelial cells undergoing
      transforming growth factor-beta-mediated mesenchymal transition express several
      other secreted profibrotic factors and are capable of activating lung
      fibroblasts. These studies provide direct evidence that activated epithelial
      cells produce mesenchymal proteins that initiate a cycle of fibrogenic effector
      cell activation, leading to progressive fibrosis. Therapy targeted at epithelial
      cell production of type I collagen offers a novel pathway for abrogating this
      progressive cycle and for limiting tissue fibrosis but may lead to sustained lung
      injury/inflammation. 

PMID- 24012678
TI  - The regulation of SOX7 and its tumor suppressive role in breast cancer.
AB  - Both epigenetic silencing and genetic deletion of tumor suppressors contribute to
      the development and progression of breast cancer. SOX7 is a transcription factor
      important to development, and its down-regulation has been reported in tumor
      tissues and cell lines of prostate, colon, and lung cancers. However, the
      regulation of SOX7 expression and its functional role in breast cancer have not
      been reported. The current study demonstrates that SOX7 mRNA and protein
      expression are down-regulated in breast cancer tissues and cell lines compared
      with adjacent normal tissues and nontumorigenic cells, respectively. The SOX7
      promoter is hypermethylated in breast cancer cell lines compared with
      nontumorigenic cells, and the inhibition of DNA methylation increases SOX7 mRNA
      levels. With shRNA-mediated SOX7 silencing, nontumorigenic immortal breast cells
      display increased proliferation, migration, and invasion and form structures that
      resemble that of breast cancer cells in a three-dimensional culture system.
      Conversely, ectopic SOX7 expression inhibits proliferation, migration, and
      invasion of breast cancer cells in vitro and tumor growth in vivo. Importantly,
      we discovered that SOX7 transcript levels positively correlated with clinical
      outcome of 674 breast cancer patients. Overall, our data suggest that SOX7 acts
      as a tumor suppressor in breast cancer. SOX7 expression is likely regulated by
      multiple mechanisms and potentially serves as a prognostic marker for breast
      cancer patients. 

PMID- 24012679
TI  - Progesterone signaling inhibits cervical carcinogenesis in mice.
AB  - Human papillomavirus is the main cause of cervical cancer, yet other nonviral
      cofactors are also required for the disease. The uterine cervix is a hormone
      responsive tissue, and female hormones have been implicated in cervical
      carcinogenesis. A transgenic mouse model expressing human papillomavirus
      oncogenes E6 and/or E7 has proven useful to study a mechanism of hormone actions
      in the context of this common malignancy. Estrogen and estrogen receptor alpha
      are required for the development of cervical cancer in this mouse model. Estrogen
      receptor alpha is known to up-regulate expression of the progesterone receptor,
      which, on activation by its ligands, either promotes or inhibits carcinogenesis,
      depending on the tissue context. Here, we report that progesterone receptor
      inhibits cervical and vaginal epithelial cell proliferation in a ligand-dependent
      manner. We also report that synthetic progestin medroxyprogesterone acetate
      promotes regression of cancers and precancerous lesions in the female lower
      reproductive tracts (ie, cervix and vagina) in the human papillomavirus
      transgenic mouse model. Our results provide the first experimental evidence that
      supports the hypothesis that progesterone signaling is inhibitory for cervical
      carcinogenesis in vivo.

PMID- 24012681
TI  - Sensory stimulation induces tensor fields, which specifically transform brain
      activity.
AB  - It was recently shown that brain activity can be represented as a stimulation
      specific vector field. Since the vector field of brain activity is specifically
      transformed by sensory input, we suggested that a tensor field that transforms
      brain activity reflects sensory input. We calculated the tensor fields that
      transform brain activity between visual baseline and auditory word processing in
      PET data and between environmental sounds and auditory word processing in fMRI
      data. In the first comparison, significant clusters formed a distributed network
      over the brain cortex. In the second comparison, clusters were more localised in
      the temporo-frontal network of speech processing. Our study therefore
      demonstrated that tensor fields reflect the sensory input that specifically
      transforms brain activity. 

PMID- 24012680
TI  - IL-17A synergistically enhances bile acid-induced inflammation during obstructive
      cholestasis.
AB  - During obstructive cholestasis, increased concentrations of bile acids activate
      ERK1/2 in hepatocytes, which up-regulates early growth response factor 1, a key
      regulator of proinflammatory cytokines, such as macrophage inflammatory protein 2
      (MIP-2), which, in turn, exacerbates cholestatic liver injury. Recent studies
      have indicated that IL-17A contributes to hepatic inflammation during obstructive
      cholestasis, suggesting that bile acids and IL-17A may interact to regulate
      hepatic inflammatory responses. We treated mice with an IL-17A neutralizing
      antibody or control IgG and subjected them to bile duct ligation. Neutralization
      of IL-17A prevented up-regulation of proinflammatory cytokines, hepatic
      neutrophil accumulation, and liver injury, indicating an important role for IL
      17A in neutrophilic inflammation during cholestasis. Treatment of primary mouse
      hepatocytes with taurocholic acid (TCA) increased the expression of MIP-2. Co
      treatment with IL-17A synergistically enhanced up-regulation of MIP-2 by TCA. In
      contrast to MIP-2, IL-17A did not affect up-regulation of Egr-1 by TCA,
      indicating that IL-17A does not affect bile acid-induced activation of signaling
      pathways upstream of early growth response factor 1. In addition, bile acids
      increased expression of IL-23, a key regulator of IL-17A production in
      hepatocytes in vitro and in vivo. Collectively, these data identify bile acids as
      novel triggers of the IL-23/IL-17A axis and suggest that IL-17A promotes hepatic
      inflammation during cholestasis by synergistically enhancing bile acid-induced
      production of proinflammatory cytokines by hepatocytes.

PMID- 24012682
TI  - Repeated resveratrol treatment attenuates methamphetamine-induced hyperactivity
      and [3H]dopamine overflow in rodents.
AB  - Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been investigated for its
      potential as a prophylactic against degenerative diseases. It is a sirtulin
      activator that has recently been shown to regulate dopaminergic systems that
      contribute to the behavioral effects of methamphetamine and cocaine. The present
      study examined the impact of resveratrol on stimulant neuropsychopharmacology in
      rodents. Acute resveratrol treatment (20-40mg/kg) was ineffective to alter
      methamphetamine (0.5mg/kg)-induced hyperactivity in mice. Rodents received
      resveratrol once-daily for seven days to determine the effect of repeated
      polyphenolic treatment. Repeated resveratrol treatment (1-20mg/kg) decreased
      methamphetamine (0.5mg/kg)-induced hyperactivity in mice. Methamphetamine's (0.1
      60MUM) efficacy to evoke [(3)H]overflow from rat striatal slices preloaded with
      [(3)H]dopamine was also attenuated by repeated resveratrol (1mg/kg) treatment.
      Repeated resveratrol treatment (10-20mg/kg) did not affect cocaine-induced
      hyperactivity in mice. Overall, these data suggest that resveratrol appears to
      have metaplastic and prophylactic activity to minimize the effects of
      methamphetamine to increase locomotor activity and evoke dopamine release. These
      data encourage future research to further investigate the relationship between
      polyphenolics and psychostimulant abuse and dependence. 

PMID- 24012683
TI  - Discovery, synthesis and biological evaluation of cycloprotoberberine derivatives
      as potential antitumor agents.
AB  - A series of new 1,13-cycloprotoberberine derivatives defined through variations
      at the 9-position were designed, synthesized and evaluated for their
      cytotoxicities in human HepG2 (hepatoma), HT1080 (fibrosarcoma) and HCT116 (colon
      cancer) cells. The preliminary structure-activity relationship (SAR) revealed
      that the replacement of 9-methoxyl with an ester moiety might significantly
      enhance the antiproliferative activity in vitro. Notably, compound 7f
      demonstrated equipotent cytotoxicity activity against breast cancer MCF-7
      (parent) and doxorubicin (DOX)-resistant MCF-7 (MCF-7/ADrR) cells, indicating a
      mode of action different from that of DOX. Further mechanism study showed that 7f
      significantly inhibited activity of DNA topoisomerase I (Top I) and Top II. G2/M
      phase arrest and tumor cell growth reduction was observed thereafter. Thus, we
      consider cycloprotoberberine analogues to be a new family of promising antitumor
      agents with an advantage of inhibiting drug-resistant cancer cells. 

PMID- 24012684
TI  - Effects of repetitive or intensified instructions in telephone assisted,
      bystander cardiopulmonary resuscitation: an investigator-blinded, 4-armed,
      randomized, factorial simulation trial.
AB  - BACKGROUND: Compression depth is frequently suboptimal in cardiopulmonary
      resuscitation (CPR). We investigated effects of intensified wording and/or
      repetitive target depth instructions on compression depth in telephone-assisted,
      protocol driven, bystander CPR on a simulation manikin. METHODS: Thirty-two
      volunteers performed 10 min of compression only-CPR in a prospective,
      investigator-blinded, 4-armed, factorial setting. Participants were randomized
      either to standard wording ("push down firmly 5 cm"), intensified wording ("it is
      very important to push down 5 cm every time") or standard or intensified wording
      repeated every 20s. Three dispatchers were randomized to give these instructions.
      Primary outcome was relative compression depth (absolute compression depth minus
      leaning depth). Secondary outcomes were absolute distance, hands-off times as
      well as BORG-scale and nine-hole peg test (NHPT), pulse rate and blood pressure
      to reflect physical exertion. We applied a random effects linear regression
      model. RESULTS: Relative compression depth was 35 +/- 10 mm (standard) versus 31
      +/- 11 mm (intensified wording) versus 25 +/- 8 mm (repeated standard) and 31 +/-
      14 mm (repeated intensified wording). Adjusted for design, body mass index and
      female sex, intensified wording and repetition led to decreased compression depth
      of 13 (95%CI -25 to -1) mm (p=0.04) and 9 (95%CI -21 to 3) mm (p=0.13),
      respectively. Secondary outcomes regarding intensified wording showed significant
      differences for absolute distance (43 +/- 2 versus 20 (95%CI 3-37) mm; p=0.01)
      and hands-off times (60 +/- 40 versus 157 (95%CI 63-251) s; p=0.04). CONCLUSION:
      In protocol driven, telephone-assisted, bystander CPR, intensified wording and/or
      repetitive target depth instruction will not improve compression depth compared
      to the standard instruction.

PMID- 24012685
TI  - Brain survival: what does the heart say?

PMID- 24012686
TI  - Direction of first bystander call for help is associated with outcome from out-of
      hospital cardiac arrest.
AB  - BACKGROUND: Preventable bystander delays following out-of-hospital cardiac arrest
      (OHCA) are common, and include bystanders inappropriately directing their calls
      for help. METHODS: We retrospectively extracted Utstein-style data from the
      Victorian Ambulance Cardiac Arrest Registry (VACAR) for adult OHCA occurring in
      Victoria, Australia, between July 2002 and June 2012. Emergency medical service
      (EMS) witnessed events were excluded. Cases were assigned into two groups on the
      basis of the first bystander call for help being directed to EMS. Study outcomes
      were: likelihood of receiving EMS treatment; survival to hospital, and; survival
      to hospital discharge. RESULTS: A total of 44499 adult OHCA cases attended by EMS
      were identified, of which first bystander calls for help were not directed to EMS
      in 2842 (6.4%) cases. Calls to a relative, friend or neighbour accounted for
      almost 60% of the total emergency call delays. Patient characteristics and
      survival outcomes were consistently less favourable when calls were directed to
      others. First bystander call to others was independently associated with older
      age, male gender, arrest in private location, and arrest in a rural region. The
      risk-adjusted odds of treatment by EMS (OR 1.33, 95% CI 1.20-1.48), survival to
      hospital (OR 1.64, 95% CI 1.37-1.96) and survival to hospital discharge (OR 1.64,
      95% CI 1.13-2.36) were significantly improved if bystanders called EMS first.
      CONCLUSION: The frequency of inappropriate bystander calls following OHCA was
      low, but associated with a reduced likelihood of treatment by EMS and poorer
      survival outcomes.

PMID- 24012687
TI  - Treatment approaches including fecal microbiota transplantation for recurrent
      Clostridium difficile infection (RCDI) among infectious disease physicians.
AB  - BACKGROUND: Clostridium difficile infection (CDI) was the most common nosocomial
      infection in the U.S. in 2010. Most cases of CDI respond to a standard course of
      antibiotics, but recurrent C. difficile infections (RCDI) are increasingly
      common. Given the lack of randomized clinical trials, it is important to
      understand how infectious disease physicians are managing RCDI to inform future
      clinical research. METHODS: An electronic survey was conducted among members of
      the Emerging Infections Network (EIN) in October 2012. Respondents were asked to
      answer specific questions about their treatment approaches toward patients with
      CDI, including fecal microbiota transplantation (FMT). RESULTS: The overall
      response rate was 621/1212 (51%). The vast majority of respondents had cared for
      small to moderate numbers of patients with CDI over the prior 6 months, and
      reported recurrence rates were consistent with published data. Preferred
      treatment regimens for RCDI showed significant variance from recommendations
      published in national guidelines. Eighty percent (424/527) of the respondents
      would consider FMT for patients with RCDI, and of 149 who had FMT available at
      their institution, 107 (72%) had actually treated >1 patient with FMT in the
      preceding year. However, significant barriers to institutional adoption of FMT
      remain for many respondents, despite very good success rates with its use.
      CONCLUSIONS: Physicians who regularly care for patients with CDI use a variety of
      treatment approaches for treating severe or recurrent CDI cases. The results of
      our survey demonstrate that FMT is used by a growing number of infectious disease
      providers as an effective and safe treatment alternative for patients with
      multiple recurrences of C. difficile infection.

PMID- 24012688
TI  - Can fungal zoospores be the source of energy for the rumen protozoa Eudiplodinium
      maggii?
AB  - Results of our earlier studies showed the ability of ciliates Eudiplodinium
      maggii to digest and metabolize commercial chitin. The natural source of this
      polysaccharide in the rumen are fungi. The objectives of present research were to
      determine the effect of fungal zoospores on the survival and population density
      of E. maggii to quantify the concentration of chitin in the cells of protozoa and
      to examine the ability of E. maggii, to ferment chitin of fungal zoospores. The
      cultivation experiment showed that the survival of protozoa was shorter than 4
      days when the culture medium was composed of buffer solution and lyophilized
      fungal spores. An enrichment of this medium with wheat gluten prolonged the
      survival of ciliates up to 8 days. The supplementation of the last medium with
      meadow hay enabled the protozoa to survive for 28 days but a positive effect was
      observed only during the last 8 days of experiment. The chitin content was 0.27
      ng and 0.21-0.35 ng per single zoospore and ciliate, respectively. An increase in
      the concentration of volatile fatty acids (VFA) was found when protozoa were
      incubated with zoospores. The production rate of VFA was 46.3 pM/protozoan per h
      whereas the endogenous production did not exceed 31 pM/protozoan per h. The molar
      proportion of acetic acid was 77.7% and these of butyric and propionic acids-12.2
      and 11.0%, respectively. The obtained results make it evident that carbohydrates
      present in fungal zoospores were utilized by protozoa in energy yielding
      processes. 

PMID- 24012689
TI  - Does HIV increase the risk of spousal violence in sub-Saharan Africa?
AB  - Although a positive association is found between HIV prevalence and intimate
      partner violence, a causal interpretation is hard to establish due to the
      endogeneity of HIV prevalence. Using the distance from the origin of the virus as
      an instrument, I find that an exogenous increase in HIV prevalence in a cluster
      has a sizable positive effect on the risk of physical and sexual violence against
      women within marriage. The results of this study confirm a gender-specific
      negative externality of the disease and encourage policy efforts to incorporate
      services for violence against women into existing HIV programs. 

PMID- 24012691
TI  - TOPK and PTEN participate in CHFR mediated mitotic checkpoint.
AB  - Mitotic progression is regulated by co-ordinated action of several proteins and
      is crucial for the maintenance of genomic stability. CHFR (Check point protein
      with FHA and RING domains) is an E3 ubiquitin ligase and a checkpoint protein
      that regulates entry into mitosis. But the molecular players involved in CHFR
      mediated mitotic checkpoint are not completely understood. In this study, we
      identified TOPK/PBK, a serine/threonine kinase and PTEN, a lipid phosphatase to
      play an important role in CHFR mediated mitotic transitions. We demonstrated that
      CHFR ubiquitinates and regulates TOPK levels, which is essential for its
      checkpoint function. Moreover, TOPK phosphorylates and inactivates PTEN, which in
      turn activates Akt that leads to proper G2/M progression. Collectively, our
      results reveal TOPK and PTEN as new players in CHFR mediated mitotic checkpoint. 

PMID- 24012690
TI  - More attention when speaking: does it help or does it hurt?
AB  - Paying selective attention to a word in a multi-word utterance results in a
      decreased probability of error on that word (benefit), but an increased
      probability of error on the other words (cost). We ask whether excitation of the
      prefrontal cortex helps or hurts this cost. One hypothesis (the resource
      hypothesis) predicts a decrease in the cost due to the deployment of more
      attentional resources, while another (the focus hypothesis) predicts even greater
      costs due to further fine-tuning of selective attention. Our results are more
      consistent with the focus hypothesis: prefrontal stimulation caused a reliable
      increase in the benefit and a marginal increase in the cost of selective
      attention. To ensure that the effects are due to changes to the prefrontal
      cortex, we provide two checks: We show that the pattern of results is quite
      different if, instead, the primary motor cortex is stimulated. We also show that
      the stimulation-related benefits in the verbal task correlate with the
      stimulation-related benefits in an N-back task, which is known to tap into a
      prefrontal function. Our results shed light on how selective attention affects
      language production, and more generally, on how selective attention affects
      production of a sequence over time. 

PMID- 24012692
TI  - High TMPRSS4 expression is a predictor of poor prognosis in cervical squamous
      cell carcinoma.
AB  - OBJECTIVE: The aim of this study was to clarify the clinical role of TMPRSS4
      expression in cervical squamous cell carcinoma (CSCC) and to investigate the role
      of TMPRSS4 in predicting outcomes of patients with CSCC. METHODS: The
      retrospective study enrolled 87 patients diagnosed with CSCC between 2004 and
      2006. TMPRSS4 expression in CSCC was assessed by immunohistochemistry, and data
      on clinical variables were collected by retrospective chart review. The impact of
      TMPRSS4 expression on 5-year disease-free survival (DFS) and 5-year overall
      survival (OS) was assessed by Kaplan-Meier analysis and Cox proportional hazards
      modeling. RESULTS: The high expression of TMPRSS4 was 63.2% in 87 patients with
      CSCC, and 17.5% in 40 patients with benign cervical disease (P<0.001). High
      TMPRSS4 expression was significantly associated with tumor grade (P=0.005), lymph
      node metastasis (P=0.004), and deep cervical stromal invasion (P=0.025). Patients
      with high expression of TMPRSS4 had shorter OS and DFS than those with low
      expression (P=0.0205 and P=0.0318, respectively). In multivariate Cox regression
      analysis, high expression of TMPRSS4 was a potential prognostic indicator for OS
      (P=0.041) and DFS (P=0.015). CONCLUSION: Our findings suggest that TMPRSS4 might
      play an important role in the progression of CSCC. TMPRSS4 could be a potential
      prognostic marker of CSCC.

PMID- 24012693
TI  - Prognostic values of osteopontin-c, E-cadherin and beta-catenin in breast cancer.
AB  - OBJECTIVE: To determine the correlation of cell adhesion molecules (osteopontin
      c, E-cadherin and beta-catenin) with clinicopathological characteristics in
      breast cancer. METHODS: Immunostaining of osteopontin-c, E-cadherin and beta
      catenin were conducted in 170 samples of breast cancer and 30 samples of adjacent
      normal breast tissues. The correlation of osteopontin-c, E-cadherin and beta
      catenin expression level with clinicopathological characteristics was evaluated
      by Pearson's chi-square and Wilcoxon rank-sum test. Univariate and multivariate
      Cox hazard regression model was used to assess the prognostic values of
      osteopontin-c, E-cadherin and beta-catenin in clinical outcome of breast cancer.
      RESULTS: A higher level of osteopontin-c whereas lower levels of E-cadherin and
      beta-catenin were observed in breast cancer as compared with the normal breast
      tissues. The expression of osteopontin-c was negatively associated with the
      expression of E-cadherin and beta-catenin. The expression of osteopontin-c
      correlated with lymph node metastasis, and advanced TNM stage and histologic
      grade. The expression of E-cadherin correlated with low histologic grade; and
      beta-catenin with low TNM stage and histological grade. Moreover, high
      osteopontin-c level correlated with tumor recurrence or metastasis as well as
      triple negative subtype. The expression of osteopontin-c was an independent
      prognostic factor for both disease-free and overall survival of breast cancer
      patients. CONCLUSION: The data suggest that the expression of osteopontin-c could
      serve as a prognostic factor of breast cancer.

PMID- 24012694
TI  - Effects of polymorphisms in translesion DNA synthesis genes on lung cancer risk
      and prognosis in Chinese men.
AB  - PURPOSE: Translesion DNA synthesis (TLS) plays an important role in promoting
      replication through DNA lesions. Genetic polymorphisms in TLS genes may have
      potential roles in lung cancer development in humans. METHODS: We evaluated the
      association between genetic variants in six TLS genes and the risk and survival
      of lung cancer in a case-control study in China. Included in the study are 224
      lung cancer patients and 448 healthy controls. RESULTS: Carriers of the G allele
      of POLkappa rs5744724 had significantly reduced risk of lung cancer (odds ratio
      (OR)=0.62, 95% confidence interval (CI): 0.44-0.89), comparing with those
      carrying the C allele, and the AA genotype of PCNA rs25406 was also associated
      with significantly decreased cancer risk compared with the major homozygote
      alleles (OR=0.47, 95% CI: 0.25-0.86). Haplotype analysis showed that subjects
      with the POLkappa C-G (rs5744533-rs5744724) haplotype had decreased risk of lung
      cancer (OR=0.69, 95% CI: 0.49-0.98), comparing with those carrying the C-C
      haplotype. Besides, the heterozygote of REV1 rs3087386 and rs3792136 were
      independent prognostic factors for lung cancer survival with hazard radio (HR)
      1.54 (95% CI: 1.12-2.12) and 1.44 (95% CI: 1.06-1.97) respectively. CONCLUSIONS:
      Our findings suggested that genetic variants in POLkappa and PCNA genes may play
      roles in the susceptibility of lung cancer, and REV1 gene may have roles in lung
      cancer survival in Chinese men.

PMID- 24012695
TI  - Simultaneous prediction of hyperglycemia and dyslipidemia in school children in
      Santa Catarina State, Brazil based on waist circumference measurement.
AB  - OBJECTIVES: Waist circumference (WC) is highly associated with metabolic risk
      factor clusters (RFC) for chronic non-communicable diseases (NCDs). In this
      study, we evaluated the use of WC measurements to detect hyperglycemia and
      dyslipidemia in children and adolescents using the WC cutoff points reported in
      the Bogalusa Heart study and the New Zealand study. DESIGN AND METHODS: Students
      (n=1011; aged 6 to 14years) were enrolled in a cross-sectional study.
      Anthropometric indices, fasting glucose, and lipid profiles were measured. The
      associations between WC measures and serum parameters were investigated by
      logistic regression models, and the clinical accuracy of the studied parameters
      was assessed using receiver operating characteristic (ROC) curve analysis.
      RESULTS: The prevalence of increased WC was 30.2% using the New Zealand cutoff
      points and 13.7% using the Bogalusa cutoff values. In general, children with
      increased WC exhibited higher concentrations of total cholesterol, triglycerides,
      LDL-cholesterol, and non-HDL-cholesterol and lower levels of HDL-cholesterol. The
      areas under the ROC curves (AUC) of the WC measurements were 0.770 (95% CI: 0.744
      0.797) and 0.600 (95% CI: 0.569-0.631) using, respectively, the New Zealand and
      Bogalusa cutoff points for WC, indicating the prediction of simultaneous
      hyperglycemia, increased levels of non-HDL-cholesterol, and reduced HDL
      cholesterol for students with increased WC. There was a significant difference
      between AUC values (P=0.001). Furthermore, the sensitivity of using WC for
      detecting RFC in students was 2.0 to 2.5-fold higher with the New Zealand study
      cutoff values for WC than with those from the Bogalusa study. Logistic regression
      analysis revealed that increased WC was associated with simultaneous
      hyperglycemia and dyslipidemia after controlling for differences in sex and age
      (P<0.01 for all). CONCLUSIONS: Children and adolescents exhibited a high
      prevalence of increased WC associated with other RFCs for NCDs. Increased WC may
      be used to screen and identify students with elevated clusters of metabolic risk
      factors for NCDs.

PMID- 24012696
TI  - Immunosuppressant therapeutic drug monitoring by LC-MS/MS: workflow optimization
      through automated processing of whole blood samples.
AB  - OBJECTIVES: Although, due to its high specificity and sensitivity, LC-MS/MS is an
      efficient technique for the routine determination of immunosuppressants in whole
      blood, it involves time-consuming manual sample preparation. The aim of the
      present study was therefore to develop an automated sample-preparation protocol
      for the quantification of sirolimus, everolimus and tacrolimus by LC-MS/MS using
      a liquid handling platform. METHODS: Six-level commercially available blood
      calibrators were used for assay development, while four quality control materials
      and three blood samples from patients under immunosuppressant treatment were
      employed for the evaluation of imprecision. Barcode reading, sample re
      suspension, transfer of whole blood samples into 96-well plates, addition of
      internal standard solution, mixing, and protein precipitation were performed with
      a liquid handling platform. After plate filtration, the deproteinised
      supernatants were submitted for SPE on-line. The only manual steps in the entire
      process were de-capping of the tubes, and transfer of the well plates to the HPLC
      autosampler. RESULTS: Calibration curves were linear throughout the selected
      ranges. The imprecision and accuracy data for all analytes were highly
      satisfactory. The agreement between the results obtained with manual and those
      obtained with automated sample preparation was optimal (n=390, r=0.96). In daily
      routine (100 patient samples) the typical overall total turnaround time was less
      than 6h. CONCLUSIONS: Our findings indicate that the proposed analytical system
      is suitable for routine analysis, since it is straightforward and precise.
      Furthermore, it incurs less manual workload and less risk of error in the
      quantification of whole blood immunosuppressant concentrations than conventional
      methods.

PMID- 24012697
TI  - Clinical and prognostic implications of circulating pentraxin 3 levels in non ST
      elevation acute coronary syndrome.
AB  - OBJECTIVES: Pentraxin 3 (PTX3) is the prototype of the long pentraxin family.
      PTX3 is involved in inflammatory processes affecting the cardiovascular system,
      and PTX3 levels have been shown to be elevated and independently prognostic in ST
      elevation myocardial infarction. Data on PTX3 levels in non-ST-elevation acute
      coronary syndrome (NSTE-ACS), in contrast, are limited. The aim of the present
      analysis was to investigate the implications of PTX3 levels in a fairly large
      sample of NSTE-ACS patients and in comparison to levels of C-reactive protein
      (CRP). DESIGN AND METHODS: We measured levels of PTX3 and CRP in both 82 healthy
      controls and 401 NSTE-ACS patients from the GUSTO IV study, and studied the
      associations of these biomarkers to clinical data and 1-year mortality. RESULTS:
      NSTE-ACS patients had significantly higher median PTX3 levels compared to healthy
      controls (3.8 vs. 1.9 MUg/L; p<0.001). PTX3 levels in patients with NSTE-ACS were
      independently related to female sex and cardiac troponin T levels, but not to age
      or cardiovascular risk factors. PTX3 levels were higher in patients who died
      within 1 year but did not emerge as an independent predictor of 1-year mortality
      (adjusted OR 1.2 [95% CI 0.6-2.3]). This was in contrast to CRP (adjusted OR 1.5
      [95% CI 1.1-2.3]). Neither PTX3 nor CRP yielded significant discriminative value
      regarding mortality prediction. CONCLUSIONS: PTX3 levels are elevated in NSTE
      ACS. However, the prognostic information provided by PTX3 levels is limited and
      inferior compared to CRP. Our data, thus, do not support the measurement of PTX3
      in patients with NSTE-ACS.

PMID- 24012698
TI  - Stress enhances return-based behaviors in Wistar rats during spatial navigation
      without altering spatial performance: improvement or deficit?
AB  - Stress is frequently reported to be deleterious to spatial learning and memory.
      However, there are many instances in which spatial performance is not affected by
      stress. This discrepancy observed across different studies, in addition to the
      animals' strain and gender, may be caused by the type of the task employed to
      assess stress-related behavioral changes. The present experiments set out to
      investigate the effects of repeated restraint stress (3h/21 days) on spatial
      performance within the two wet-land (Morris water task; MWT) and dry-land (the
      ziggurat task; ZT) tasks for spatial learning and memory in adult male Wistar
      rats. All rats were tested before and after stress treatment. Stressed rats
      gained less weight than controls. Stress also enhanced circulating corticosterone
      (CORT). We did not observe a deleterious effect of stress on spatial learning and
      memory in either of the tasks: both groups successfully performed the wet- and
      dry-land tasks across all spatial testing days, indicating intact spatial
      cognition in control and stress rats. However, daily restraint stress for 21 days
      significantly caused enhancement in rats' memory-dependent returns during the
      goal-directed investigation in the ZT. The number of returns on learning days was
      not affected by repeated restraint stress. Return-based spatial investigation
      induced by stress only on memory days in the dry-land task, not only emphasize on
      the task-dependent nature of stress-related alterations, it may reveal one of the
      silent, but arguably deleterious effects of stress on spatial memory in Wistar
      rats.

PMID- 24012699
TI  - Composition analysis and anti-proliferation activity of polysaccharides from
      Dendrobium chrysotoxum.
AB  - Water-soluble polysaccharides (DCCP, DCPP) were extracted from the stems of
      Dendrobium chrysotoxum using boiling water and ultrasound. DCPP were successively
      purified by chromatography on DEAE-Cellulose-52 and Sephadex G-200 column, giving
      three major polysaccharide fractions termed DCPP-I, DCPP-I-a and DCPP-II. Among
      these fractions, DCPP-I-a exhibited the highest abundance (79.5%). The number
      average molecular weight and weight-average molecular weight of DCPP-I-a were 67
      kDa and 122 kDa, respectively. Monosaccharide components analysis indicated that
      DCPP-I-a were composed of xylose, glucose, galactose in a molar ratio of
      1.44:6.93:12.79. Infrared spectra (IR) and (1)H NMR showed that DCPP-I-a was
      composed of a beta-D pyran ring with a beta-configuration. The evaluation of anti
      proliferation activity suggested that DCPP-I-a and DCPP-II had a higher
      inhibitory effect on the SPC-A-1 cells than DCCP as determined with in vitro anti
      proliferation test.

PMID- 24012700
TI  - Raman spectroscopic analysis of combat-related heterotopic ossification
      development.
AB  - Over 60% of our severely combat-injured patient population develops
      radiographically apparent heterotopic ossification. Nearly a third of these
      require surgical excision of symptomatic lesions, a procedure that is fraught
      with complications, and delays or regresses functional rehabilitation in many
      cases. Unfortunately, for the combat injured, medical contraindications and
      logistical limitations limit widespread use of conventional means of primary
      prophylaxis. Better means of risk stratification are needed to both mitigate the
      risk of current means of primary prophylaxis as well as to evaluate novel
      preventive strategies currently in development. We asked whether Raman spectral
      changes, measured ex vivo, correlated with histologic evidence of the earliest
      signs of HO formation using tissue biopsies from the wounds of combat casualties.
      In doing so, we compared normal muscle tissue to injured muscle tissue,
      unmineralized HO tissue, and mineralized HO tissue. The Raman spectra of these
      tissues demonstrate clear differences in the amide I and amide III spectral
      regions of HO tissue compared to normal tissue, denoted by changes in the
      1640/1445cm(-1)(p<0.01), and 1340/1270cm(-1) (p<0.01) band area ratios (BARs).
      Additionally, analysis of the bone mineral in HO by Raman spectroscopy appears
      capable of determining bone maturity by measuring both the 945/960cm(-1) and the
      1070/1445cm(-1) BARs. Raman may therefore prove a useful, non-invasive, and early
      diagnostic modality to detect HO formation prior to it becoming evident
      clinically or radiographically. This technique could ostensibly be utilized as a
      non-invasive means to risk stratify individual wounds at a time thought to be
      amenable to various means of primary prophylaxis. 

PMID- 24012701
TI  - A two-year history of high bone loading physical activity attenuates ethnic
      differences in bone strength and geometry in pre-/early pubertal children from a
      low-middle income country.
AB  - We examined the interplay between ethnicity and weight-bearing physical activity
      on the content and volumetric properties of bone in a pre- to early pubertal
      South African Black and White population. Sixty six children [Black boys, 10.4
      (1.4)yrs, n=15; Black girls, 10.1 (1.2)yrs, n=27; White boys, 10.1 (1.1)yrs, n=7;
      White girls, 9.6 (1.3)yrs, n=17] reported on all their physical activities over
      the past two years in an interviewer administered physical activity questionnaire
      (PAQ). All participants underwent a whole body and site-specific DXA scan and we
      also assessed bone structure and estimated bone strength with pQCT. Children were
      classified as being either high or low bone loaders based on the cohort's median
      peak bone strain score estimated from the PAQ. In the low bone loading group,
      Black children had greater femoral neck bone mineral content (BMC) (2.9 (0.08)g)
      than White children (2.4 (0.11)g; p=0.05). There were no ethnic differences in
      the high bone loaders for femoral neck BMC. At the cortical site, the Black low
      bone loaders had a greater radius area (97.3 (1.3) vs 88.8 (2.6)mm(2); p=0.05)
      and a greater tibia total area (475.5 (8.7) vs. 397.3 (14.0)mm(2); p=0.001) and
      strength (1633.7 (60.1) vs. 1271.8 (98.6)mm(3); p=0.04) compared to the White low
      bone loaders. These measures were not different between the Black low and high
      bone loaders or between the Black and White high bone loaders. In conclusion, the
      present study shows that there may be ethnic and physical activity associations
      in the bone health of Black and White pre-pubertal children and further
      prospective studies are required to determine the possible ethnic specific
      response to mechanical loading. 

PMID- 24012702
TI  - Incorporation of quercetin in respirable lipid microparticles: effect on
      stability and cellular uptake on A549 pulmonary alveolar epithelial cells.
AB  - The aim of the present study was to develop controlled release inhalable lipid
      microparticles (LMs) loaded with the antioxidant flavonoid, quercetin and to
      investigate the interaction of these microparticles with A549 pulmonary alveolar
      epithelial cells. The LMs were produced using different lipidic materials and
      surfactants, by melt emulsification followed by a sonication step. The most
      efficient modulation of the in vitro release of quercetin was achieved by the LMs
      prepared with tristearin and hydrogenated phosphatidylcholine, which were used
      for subsequent studies. These LMs exhibited a quercetin loading of 11.8+/-0.3%,
      and a volume median diameter, determined by laser diffraction, of 4.1+/-0.2MUm.
      Moreover, their mass median aerodynamic diameter (4.82+/-0.15MUm) and fine
      particle fraction (27.2+/-3.9%), as measured by multi-stage liquid impinger, were
      suitable for pulmonary delivery. Quercetin was found to be highly unstable
      (complete decomposition within 6-h incubation) in Ham's F-12 medium used for A549
      cell culture. Degradation was markedly reduced (16.4% of the initial quercetin
      content still present after 24-h incubation) after encapsulation in the lipid
      particle system. Viability studies performed by lactate dehydrogenase assay,
      demonstrated that quercetin LMs showed no significant cytotoxicity on the A549
      cells, over the concentration 0.1-5MUM. The uptake of quercetin by the A549 lung
      alveolar cells was also investigated. After 4-h incubation, the accumulation of
      quercetin in the A549 cells was significantly higher (2.3-fold increase) for the
      microparticle entrapped flavonoid when compare to non-encapsulated quercetin. The
      enhanced intracellular delivery of quercetin achieved by the LMs is likely due to
      the flavonoid stabilization after encapsulation. 

PMID- 24012703
TI  - Electrochemical determination of BCR/ABL fusion gene based on in situ synthesized
      gold nanoparticles and cerium dioxide nanoparticles.
AB  - An efficient DNA electrochemical biosensor, based on the gold nanoparticles
      (GNPs) in situ synthesized at the surface of multiwalled carbon nanotubes
      (MWCNTs), cerium dioxide (CeO2) and chitosan (Chits) composite membrane, was
      developed for the detection of BCR/ABL fusion gene in chronic myelogenous
      leukemia (CML). The capture probe was attached onto the nanocomposite membrane
      modified glassy carbon electrode (GCE) through the conjugated structure. Owing to
      the synergistic effects of CeO2 nanoparticles with a strong adsorption ability
      and MWCNTs with a large surface area and excellent electron transfer ability, the
      prepared composite membrane was demonstrated an efficient electron transfer
      ability. The biosensor was electrochemically characterized by cyclic voltammogram
      (CV) and differential pulse voltammetry (DPV), and the decrease of the peak
      currents upon hybridization was observed using methylene blue (MB) as the
      electroactive indicator. Under the optimized conditions, peak currents were
      linear over the range from 1 * 10(-9) M to 1 * 10(-)(12) M, with a detection
      limit of 5 * 10(-)(13) M (based on the 3sigma). And the proposed method was
      successfully applied for the detection of PCR real samples with satisfactory
      results. Furthermore, the developed DNA biosensor was demonstrated a good
      selectivity, a reasonable stability and a favorable reproducibility, which could
      be regenerated easily. 

PMID- 24012704
TI  - Formulation and in vitro evaluation of 17-allyamino-17-demethoxygeldanamycin (17
      AAG) loaded polymeric mixed micelles for glioblastoma multiforme.
AB  - Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary
      brain tumor in human. 17-Allylamino-17-demethoxy geldanamycin (17-AAG) is an
      inhibitor of heat shock protein 90 (HSP90). The highly lipophilic nature and
      selective targeting of tumor cells makes 17-AAG a promising candidate for therapy
      of GBMs but poor water solubility, short biological half-life and hepatotoxicity
      limited its clinical use. Polymeric mixed micelles composed of Pluronic(r) P-123
      and F-127 (2:1 (w/w)) containing 17-AAG were prepared and characterized. Cellular
      uptake and in vitro cytotoxicity of the prepared micelles were determined in
      U87MG human glioblastoma cells. The particle size of 17-AAG loaded Pluronic((r))
      P-123 and F-127 mixed micelles was 22.2 +/- 0.1 nm; drug loading was about 4.0 +/
      0.5% (w/w) with 88.2 +/- 3.1% (w/w) encapsulation efficiency. About 90% of drug
      was released from the nanoparticles over 8 days. Cellular uptake studies showed
      intracellular uptake of mixed micelles. Cytotoxicity study showed 5-fold increase
      (P < 0.05, n = 3) in the cytotoxicity of 17-AAG-loaded mixed micelles to free 17
      AAG. Due to their targeting ability, size, high drug loading and controlled
      release behavior, 17-AAG loaded Pluronic((r)) P-123 and F-127 mixed micelles
      might be developed as a delivery system for GBM treatment. 

PMID- 24012705
TI  - Durable contact active antimicrobial materials formed by a one-step covalent
      modification of polyvinyl alcohol, cellulose and glass surfaces.
AB  - In this work we have applied a direct covalent linkage of quaternary ammonium
      salts (QAS) to prepare a series of contact active antimicrobial surfaces based on
      widely utilized materials. Formation of antimicrobial polyvinyl alcohol (PVA
      QAS), cellulose (cellulose-QAS) and glass (glass-QAS) surfaces was achieved by
      one step synthesis with no auxiliary linkers. The X-ray photoelectron
      spectroscopy (XPS) revealed tridentate binding mode of the antimicrobial agent.
      The antimicrobial activity of the prepared materials was tested on Bacillus
      cereus, Alicyclobacillus acidoterrestris, Escherichia coli and Pseudomonas
      aeruginosa. Active site density of the modified materials was examined and found
      to correlate with their antimicrobial activity. Stability studies at different pH
      values and temperatures confirmed that the linkage of the bioactive moiety to the
      surface is robust and resistant to a range of pH and temperatures. Prolonged long
      term effectiveness of the contact active materials was demonstrated by their
      repeated usage, without loss of the antimicrobial efficacy. 

PMID- 24012706
TI  - Establishing the level of safety concern for chemicals in food without the need
      for toxicity testing.
AB  - There is demand for methodologies to establish levels of safety concern
      associated with dietary exposures to chemicals for which no toxicological data
      are available. In such situations, the application of in silico methods appears
      promising. To make safety statement requires quantitative predictions of
      toxicological reference points such as no observed adverse effect level and
      carcinogenic potency for DNA-reacting chemicals. A decision tree (DT) has been
      developed to aid integrating exposure information and predicted toxicological
      reference points obtained with quantitative structure activity relationship
      ((Q)SAR) software and read across techniques. The predicted toxicological values
      are compared with exposure to obtain margins of exposure (MoE). The size of the
      MoE defines the level of safety concern and should account for a number of
      uncertainties such as the classical interspecies and inter-individual variability
      as well as others determined on a case by case basis. An analysis of the
      uncertainties of in silico approaches together with results from case studies
      suggest that establishing safety concern based on application of the DT is
      unlikely to be significantly more uncertain than based on experimental data. The
      DT makes a full use of all data available, ensuring an adequate degree of
      conservatism. It can be used when fast decision making is required. 

PMID- 24012707
TI  - Considerations for the nonclinical safety evaluation of antibody drug conjugates
      for oncology.
AB  - Antibody drug conjugates (ADCs) include monoclonal antibodies that are linked to
      cytotoxic small molecules. A number of these agents are currently being developed
      as anti-cancer agents designed to improve the therapeutic index of the cytotoxin
      (i.e., cytotoxic small molecule or cytotoxic agent) by specifically delivering it
      to tumor cells. This paper presents primary considerations for the nonclinical
      safety evaluation of ADCs and includes strategies for the evaluation of the
      entire ADC or the various individual components (i.e., antibody, linker or the
      cytotoxin). Considerations are presented on how to design a nonclinical safety
      assessment program to identify the on- and off-target toxicities to enable first
      in-human (FIH) studies. Specific discussions are also included that provide
      details as to the need and how to conduct the studies for evaluating ADCs in
      genetic toxicology, tissue cross-reactivity, safety pharmacology,
      carcinogenicity, developmental and reproductive toxicology, biotransformation,
      toxicokinetic monitoring, bioanalytical assays, immunogenicity testing, test
      article stability and the selection of the FIH dose. Given the complexity of
      these molecules and our evolving understanding of their properties, there is no
      single all-encompassing nonclinical strategy. Instead, each ADC should be
      evaluated on a case-by-case scientifically-based approach that is consistent with
      ICH and animal research guidelines. 

PMID- 24012709
TI  - Advances in nanodiagnostic techniques for microbial agents.
AB  - Infectious diseases account for millions of sufferings and deaths in both
      developing as well as developed countries with a substantial economic loss.
      Massive increase in world population and international travel has facilitated
      their spread from one part of the world to other areas, making them one of the
      most significant global health risks. Furthermore, detection of bioterrorism
      agents in water, food and environmental samples as well traveler's baggage is a
      great challenge of the time for security purpose. Prevention strategies against
      infectious agents demand rapid and accurate detection and identification of the
      causative agents with highest sensitivity which should be equally available in
      different parts of the globe. Similarly, rapid and early diagnosis of infectious
      diseases has always been indispensable for their prompt cure and management,
      which has stimulated scientists to develop highly sophisticated techniques over
      centuries and the efforts continue unabated. Conventional diagnostic techniques
      are time consuming, tedious, expensive, less sensitive, and unsuitable for field
      situations. Nanodiagnostic assays have been promising for early, sensitive, point
      of-care and cost-effective detection of microbial agents. There has been an
      explosive research in this area of science in last two decades yielding highly
      fascinating results. This review highlights some of the advancements made in the
      field of nanotechnology based assays for microbial detection since 2005 along
      with providing the basic understanding. 

PMID- 24012708
TI  - Characterisation and toxicological assessment of Neutral Methacrylate Copolymer
      for GRAS evaluation.
AB  - Neutral Methacrylate Copolymer is a fully polymerised copolymer used in the
      pharmaceutical industry to permit pH-independent delayed release of active
      ingredients from oral dosage forms. This function has potential use with food
      supplements and this article describes available information on the safety of the
      substance. Oral administration of radiolabelled copolymer to rats resulted in the
      detection of chemically unchanged copolymer in the faeces, with negligible
      absorption. Safety studies revealed no adverse toxicity following repeated
      administration at doses of up to 2000 mg/kg bw/d in a sub-chronic study in rats
      or 250 mg/kg bw/d in a sub-chronic study in dogs. No reproductive toxicity
      occurred at up to 2000 mg/kg bw/d in rats or rabbits. The substance shows no
      evidence of genotoxicity, has low acute toxicity and no irritation or
      sensitisation potential. An ADI value of 20 mg/kg bw was concluded from two
      alternative approaches. Daily exposure from use in dietary supplements is
      estimated as up to 10.0 mg/kg bw in adults and 13.3 mg/kg bw in children. There
      would therefore appear to be no safety concerns under the intended conditions of
      use. The information provided is intended to support an evaluation that the
      substance may be "generally recognized as safe" (GRAS).

PMID- 24012710
TI  - Three-dimensional network of Drosophila brain hemisphere.
AB  - The first step to understanding brain function is to determine the brain's
      network structure. We report a three-dimensional analysis of the brain network of
      the fruit fly Drosophila melanogaster by synchrotron-radiation tomographic
      microscopy. A skeletonized wire model of the left half of the brain network was
      built by tracing the three-dimensional distribution of X-ray absorption
      coefficients. The obtained models of neuronal processes were classified into
      groups on the basis of their three-dimensional structures. These classified
      groups correspond to neuronal tracts that send long-range projections or repeated
      structures of the optic lobe. The skeletonized model is also composed of neuronal
      processes that could not be classified into the groups. The distribution of these
      unclassified structures correlates with the distribution of contacts between
      neuronal processes. This suggests that neurons that cannot be classified into
      typical structures should play important roles in brain functions. The
      quantitative description of the brain network provides a basis for structural and
      statistical analyses of the Drosophila brain. The challenge is to establish a
      methodology for reconstructing the brain network in a higher-resolution image,
      leading to a comprehensive understanding of the brain structure. 

PMID- 24012711
TI  - Synthesis of pyrido[2,1-a]isoquinolin-4-ones and oxazino[2,3-a]isoquinolin-4
      ones: new inhibitors of mitochondrial respiratory chain.
AB  - Benzo[a]quinolizine is an important heterocyclic framework that can be found in
      numerous bioactive compounds. The general scheme for the synthesis of these
      compounds was based on the preparation of the appropriate dihydroisoquinolines by
      Bischler-Napieralski cyclization with good yields, followed by the Pemberton
      method to form the oxazinones or pyridones derivatives via acyl-ketene imine
      cyclocondensation. All the synthesized compounds were assayed in vitro for their
      ability to inhibit mitochondrial respiratory chain. Most of the tested compounds
      were able to inhibit the integrated electron transfer chain, measured as NADH
      oxidation, which includes complexes I, III and IV, in the low micromolar range.
      Oxazino[2,3-a]isoquinolin-4-ones displayed greater activity than their pyrido[2,1
      a]isoquinolin-4-ones analogs. Indeed, the presence of a furan ring in C2 position
      of oxazino[2,3-a]isoquinolin-4-ones provided the compound (1g) with the most
      potent biological activity. Therefore, these compounds and especially the
      oxazinone derivatives are in the tendency of the new less toxic antitumor agents
      that target mitochondrial electron transport chain in a middle range potency.

PMID- 24012712
TI  - Design, synthesis, and structure-activity relationships of novel 6,7
      disubstituted-4-phenoxyquinoline derivatives as potential antitumor agents.
AB  - Two series of quinoline derivatives bearing the pyridine/pyrimidine scaffold were
      synthesized, and evaluated for their c-Met kinase inhibitory activity and
      antiproliferative activity against 5 cancer cell lines (HT-29, H460, MKN-45,
      A549, and U87MG) were evaluated in vitro. Most compounds showed moderate to
      excellent potency, and compared to foretinib, the most promising analog 18b (c
      Met half-maximal inhibitory concentration [IC50] = 1.39 nM) showed a 7.3-fold
      increase in activity against HT-29 cell line in vitro. Structure-activity
      relationship studies indicated that regulation of the electron density on the
      pyridine/pyrimidine ring to a proper degree was a key factor in improving the
      antitumor activity.

PMID- 24012713
TI  - Synthesis, characterization, antiparasitic and cytotoxic evaluation of thioureas
      conjugated to polyamine scaffolds.
AB  - A series of mono- and multimeric 4-amino-7-chloroquinoline and ferrocenyl
      thioureas have been prepared by the reaction of a 7-chloroquinoline methyl ester
      and a ferrocenylimine methyl ester with various amines. These compounds were
      characterized using standard spectroscopic and analytical techniques. The
      compounds were evaluated against the NF54 (CQ-sensitive) and Dd2 (CQ-resistant)
      strains of Plasmodium falciparum. The quinoline compounds show enhanced activity
      compared to the ferrocene compounds against this parasite. Compound 5 displays
      the most promising activity against the NF54 strain. Compounds 5 and 6 are
      effective at inhibiting beta-hematin formation perhaps due to an increased number
      of quinoline moieties. The trimeric (12) and tetrameric (13) ferrocenyl compounds
      also inhibit beta-hematin formation, albeit to a lesser degree compared to the
      quinoline thioureas. The compounds were also screened against the G3 strain of
      Trichomonas vaginalis and here the ferrocene-containing compounds show a slightly
      higher parasite growth inhibition compared to the quinoline thioureas. The
      quinoline compounds were also found to be more cytotoxic compared to the
      ferrocenyl compounds. Compound 6 displays good cytotoxicity against WHCO1
      oesophageal cancer cells.

PMID- 24012714
TI  - QSAR modeling of aromatase inhibitory activity of 1-substituted 1,2,3-triazole
      analogs of letrozole.
AB  - Aromatase is an estrogen biosynthesis enzyme belonging to the cytochrome P450
      family that catalyzes the rate-limiting step of converting androgens to
      estrogens. As it is pertinent toward tumor cell growth promotion, aromatase is a
      lucrative therapeutic target for breast cancer. In the pursuit of robust
      aromatase inhibitors, a set of fifty-four 1-substituted mono- and bis
      benzonitrile or phenyl analogs of 1,2,3-triazole letrozole were employed in
      quantitative structure-activity relationship (QSAR) study using multiple linear
      regression (MLR), artificial neural network (ANN) and support vector machine
      (SVM). Such QSAR models were developed using a set of descriptors providing
      coverage of the general characteristics of a molecule encompassing molecular
      size, flexibility, polarity, solubility, charge and electronic properties.
      Important physicochemical properties giving rise to good aromatase inhibition
      were obtained by means of exploring its chemical space as a function of the
      calculated molecular descriptors. The optimal subset of 3 descriptors (i.e.
      number of rings, ALogP and HOMO-LUMO) was further used for QSAR model
      construction. The predicted pIC50 values were in strong correlation with their
      experimental values displaying correlation coefficient values in the range of
      0.72-0.83 for the cross-validated set (QCV) while the external test set (Q(Ext))
      afforded values in the range of 0.65-0.66. Insights gained from the present study
      are anticipated to provide pertinent information contributing to the origins of
      aromatase inhibitory activity and therefore aid in our on-going quest for
      aromatase inhibitors with robust properties.

PMID- 24012716
TI  - The early research and development of ebselen.
AB  - Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one; PZ-51, DR-3305), is an
      organoselenium compound with glutathione peroxidase (GPx)-like, thiol-dependent,
      hydroperoxide reducing activity. As an enzyme mimic for activity of the
      selenoenzyme GPx, this compound has proved to be highly useful in research on
      mechanisms in redox biology. Furthermore, the reactivity of ebselen with protein
      thiols has helped to identify novel, selective targets for inhibitory actions on
      several enzymes of importance in pharmacology and toxicology. Importantly, the
      selenium in ebselen is not released and thus is not bioavailable, ebselen
      metabolites being excreted in bile and urine. As a consequence, initial concerns
      about selenium toxicity, fortunately, were unfounded. Potential applications in
      medical settings have been explored, notably in brain ischemia and stroke. More
      recently, there has been a surge in interest as new medical applications have
      been taken into consideration. The first publication on the biochemical effects
      of ebselen appeared 30 years ago (Muller et al.), which prompted the authors to
      retrace the early development from their perspective. It is a fascinating example
      of fruitful interaction between research-oriented industry and academia.

PMID- 24012717
TI  - Hybrid transvaginal NOTES cholecystectomy.

PMID- 24012715
TI  - Allopregnanolone in the brain: protecting pregnancy and birth outcomes.
AB  - A successful pregnancy requires multiple adaptations in the mother's brain that
      serve to optimise foetal growth and development, protect the foetus from adverse
      prenatal programming and prevent premature delivery of the young. Pregnancy
      hormones induce, organise and maintain many of these adaptations. Steroid
      hormones play a critical role and of particular importance is the progesterone
      metabolite and neurosteroid, allopregnanolone. Allopregnanolone is produced in
      increasing amounts during pregnancy both in the periphery and in the maternal and
      foetal brain. This review critically examines a role for allopregnanolone in both
      the maternal and foetal brain during pregnancy and development in protecting
      pregnancy and birth outcomes, with particular emphasis on its role in relation to
      stress exposure at this time. Late pregnancy is associated with suppressed stress
      responses. Thus, we begin by considering what is known about the central
      mechanisms in the maternal brain, induced by allopregnanolone, that protect the
      foetus(es) from exposure to harmful levels of maternal glucocorticoids as a
      result of stress during pregnancy. Next we discuss the central mechanisms that
      prevent premature secretion of oxytocin and consider a role for allopregnanolone
      in minimising the risk of preterm birth. Allopregnanolone also plays a key role
      in the foetal brain, where it promotes development and is neuroprotective. Hence
      we review the evidence about disruption to neurosteroid production in pregnancy,
      through prenatal stress or other insults, and the immediate and long-term adverse
      consequences for the offspring. Finally we address whether progesterone or
      allopregnanolone treatment can rescue some of these deficits in the offspring. 

PMID- 24012718
TI  - Pelvic packing.

PMID- 24012719
TI  - Structural plasticity of dendritic spines: the underlying mechanisms and its
      dysregulation in brain disorders.
AB  - Dendritic spines are specialized structures on neuronal processes where the
      majority of excitatory synapses are localized. Spines are highly dynamic, and
      their stabilization and morphology are influenced by synaptic activity. This
      extrinsic regulation of spine morphogenesis underlies experience-dependent brain
      development and information storage within the brain circuitry. In this review,
      we summarize recent findings that demonstrate the phenomenon of activity
      dependent structural plasticity and the molecular mechanisms by which synaptic
      activity sculpt neuronal connections. Impaired structural plasticity is
      associated with perturbed brain function in neurodevelopmental disorders such as
      autism. Information from the mechanistic studies therefore provides important
      insights into the design of therapeutic strategies for these brain disorders. 

PMID- 24012720
TI  - BMP-6 inhibits cell proliferation by targeting microRNA-192 in breast cancer.
AB  - Although bone morphogenetic protein-6 (BMP-6) has been identified as a tumor
      suppressor associated with breast cancer differentiation and metastasis, the
      potential roles of BMP-6 in regulating cell cycle progression have not been fully
      examined. In the present study, we provide the novel finding that induction of
      BMP-6 in MDA-MB-231 breast cancer cells significantly inhibits cell proliferation
      by decreasing the number of cells in S phase of the cell cycle, resulting in
      inhibition of tumorigenesis in a nude mouse xenograft model. Further
      investigation indicated that BMP-6 up-regulates the expression of microRNA-192
      (miR-192) in MDA-MB-231 cells. Elevated expression of miR-192 caused cell growth
      arrest, which is similar to the effect of BMP-6 induction. Importantly, depletion
      of endogenous miR-192 by miRNA inhibition significantly attenuated BMP-6-mediated
      repression of cell cycle progression. In breast cancer tissue, miR-192 expression
      is significantly down-regulated in tumor samples and positively correlates with
      the expression of BMP-6, demonstrating the inhibitory effect of BMP-6 on cell
      proliferation through miR-192 regulation. Additionally, using the RT(2) Profiler
      PCR Array, retinoblastoma 1 (RB1) was identified as a direct target of the BMP
      6/miR-192 pathway in regulating cell proliferation in breast cancer. In
      conclusion, we have identified an important role for BMP-6/miR-192 signaling in
      the regulation of cell cycle progression in breast cancer. Furthermore, BMP-6/miR
      192 was expressed at low levels in breast cancer specimens, indicating that this
      pathway might represent a promising therapeutic target for breast cancer
      treatment. 

PMID- 24012721
TI  - The nitric oxide redox sibling nitroxyl partially circumvents impairment of
      platelet nitric oxide responsiveness.
AB  - Impaired platelet responsiveness to nitric oxide (NO resistance) is a common
      characteristic of many cardiovascular disease states and represents an
      independent risk factor for cardiac events and mortality. NO resistance reflects
      both scavenging of NO by superoxide (O2(-)), and impairment of the NO receptor,
      soluble guanylate cyclase (sGC). There is thus an urgent need for circumvention
      of NO resistance in order to improve clinical outcomes. Nitroxyl (HNO), like NO,
      produces vasodilator and anti-aggregatory effects, largely via sGC activation,
      but is not inactivated by O2(-). We tested the hypothesis that HNO circumvents NO
      resistance in human platelets. In 57 subjects with or without ischemic heart
      disease, platelet responses to the HNO donor isopropylamine NONOate (IPA/NO) and
      the NO donor sodium nitroprusside (SNP) were compared. While SNP (10MUM) induced
      29+/-3% (p<0.001) inhibition of platelet aggregation, IPA/NO (10MUM) caused 75+/
      4% inhibition (p<0.001). In NO-resistant subjects (n=28), the IPA/NO:SNP response
      ratio was markedly increased (p<0.01), consistent with partial circumvention of
      NO resistance. Similarly, cGMP accumulation in platelets was greater (p<0.001)
      with IPA/NO than with SNP stimulation. The NO scavenger carboxy-PTIO (CPTIO,
      200MUM) inhibited SNP and IPA/NO responses by 92+/-7% and 17+/-4% respectively
      (p<0.001 for differential inhibition), suggesting that effects of IPA/NO are only
      partially NO-mediated. ODQ (10MUM) inhibited IPA/NO responses by 36+/-8%
      (p<0.001), consistent with a contribution of sGC/haem to IPA/NO inhibition of
      aggregation. There was no significant relationship between whole blood ROS
      content and IPA/NO responses. Thus the HNO donor IPA/NO substantially circumvents
      platelet NO resistance while acting, at least partially, as a haem-mediated sGC
      activator. 

PMID- 24012722
TI  - Why does lag affect the durability of memory-based automaticity: loss of memory
      strength or interference?
AB  - In Rickard, Lau, and Pashler's (2008) investigation of the lag effect on memory
      based automaticity, response times were faster and proportion of trials retrieved
      was higher at the end of practice for short lag items than for long lag items.
      However, during testing after a delay, response times were slower and proportion
      of trials retrieved was lower for short lag items than for long lag items. The
      current study investigated the extent to which the lag effect on the durability
      of memory-based automaticity is due to interference or to the loss of memory
      strength with time. Participants repeatedly practiced alphabet subtraction items
      in short lag and long lag conditions. After practice, half of the participants
      were immediately tested and the other half were tested after a 7-day delay.
      Results indicate that the lag effect on the durability of memory-based
      automaticity is primarily due to interference. We discuss potential modification
      of current memory-based processing theories to account for these effects. 

PMID- 24012724
TI  - The mere exposure effect for consumer products as a consequence of existing
      familiarity and controlled exposure.
AB  - The finding that repeated exposure to a stimulus enhances attitudes directed
      towards it is a well-established phenomenon. Despite this, the effects of
      exposure to products are difficult to determine given that they could have
      previously been exposed to participants any number of times. Furthermore, factors
      other than simple repeated exposure can influence affective evaluations for
      stimuli that are meaningful. In our first study, we examined the influence of
      existing familiarity with common objects and showed that the attractiveness of
      shapes representing common objects increases with their rated commonness. In our
      second study, we eliminated the effects of prior exposure by creating fictitious
      yet plausible products; thus, exposure frequency was under complete experimental
      control. We also manipulated the attention to be drawn to the products' designs
      by placing them in contexts where their visual appearance was stressed to be
      important versus contexts in which it was indicated that little attention had
      been paid to their design. Following mere exposure, attractiveness ratings
      increased linearly with exposure frequency, with the slope of the function being
      steeper for stimuli presented in an inconspicuous context-indicating that
      individuals engage in more deliberate processing of the stimuli when attention is
      drawn to their visual appearance. 

PMID- 24012725
TI  - Presence of Tube isoforms in Litopenaeus vannamei suggests various regulatory
      patterns of signal transduction in invertebrate NF-kappaB pathway.
AB  - The toll-like receptor (TLR)/NF-kappaB signaling pathways play critical roles in
      the innate immune system. The intracellular signal transduction of most TLR
      pathways in invertebrate cells is triggered by formation of a heterotrimeric
      complex composed of MyD88, Tube and Pelle. In this study, we identified a
      Litopenaeus vannamei Pelle (LvPelle) and an isoform of L. vannamei Tube (LvTube)
      designated as LvTube-1. The interactions among LvPelle, LvTube/LvTube-1 and
      LvMyD88/LvMyD88-1 were elucidated and their functions during pathogen infections
      were investigated. Knockdowns of LvPelle and LvTube/LvTube-1 using RNAi strategy
      led to higher mortalities of shrimps during Vibrio parahemolyticus infection, and
      could reduce the genome copy number of white spot syndrome virus (WSSV) in the
      infected muscle tissue but did not affect the mortality caused by WSSV infection.
      The effects of LvPelle and LvTube/LvTube-1 on promoters containing NF-kappaB
      binding motifs were analyzed by dual-luciferase reporter assays and the results
      demonstrated that LvTube-1 could activate the NF-kappaB activity to significantly
      higher level than LvTube did. Moreover, tissue distributions of LvTube and LvTube
      1 mRNAs and their expression profiles during pathogen and immune stimulant
      challenges were different, indicating that they could play different roles in
      immune responses. This is the first report of Tube isoforms in invertebrates.
      Together with our previous study on LvMyD88 isoforms, our results suggest that
      various isoforms of adaptor components may be involved in various regulatory
      patterns of signal transduction in invertebrate TLR/NF-kappaB pathway and this
      could be a strategy adopted by invertebrates to modulate immune responses.

PMID- 24012723
TI  - Are all letters really processed equally and in parallel? Further evidence of a
      robust first letter advantage.
AB  - This present study examined accuracy and response latency of letter processing as
      a function of position within a horizontal array. In a series of 4 Experiments,
      target-strings were briefly (33ms for Experiments 1 to 3, 83ms for Experiment 4)
      displayed and both forward and backward masked. Participants then made a two
      alternative forced choice. The two alternative responses differed just in one
      element of the string, and position of mismatch was systematically manipulated.
      In Experiment 1, words of different lengths (from 3 to 6 letters) were presented
      in separate blocks. Across different lengths, there was a robust advantage in
      performance when the alternative response was different for the letter occurring
      at the first position, compared to when the difference occurred at any other
      position. Experiment 2 replicated this finding with the same materials used in
      Experiment 1, but with words of different lengths randomly intermixed within
      blocks. Experiment 3 provided evidence of the first position advantage with legal
      nonwords and strings of consonants, but did not provide any first position
      advantage for non-alphabetic symbols. The lack of a first position advantage for
      symbols was replicated in Experiment 4, where target-strings were displayed for a
      longer duration (83ms). Taken together these results suggest that the first
      position advantage is a phenomenon that occurs specifically and selectively for
      letters, independent of lexical constraints. We argue that the results are
      consistent with models that assume a processing advantage for coding letters in
      the first position, and are inconsistent with the commonly held assumption in
      visual word recognition models that letters are equally processed in parallel
      independent of letter position. 

PMID- 24012726
TI  - Synthesis of novel 13alpha-18-nor-16-carboxamido steroids via a palladium
      catalyzed aminocarbonylation reaction.
AB  - 13alpha-18-nor-16-Carboxamido steroids were synthesized via a palladium-catalyzed
      aminocarbonylation reaction of the corresponding iodoalkenes. The starting
      material was an unnatural 13alpha-16-keto steroid, obtained by a Wagner-Meerwein
      rearrangement of a 16alpha,17alpha-epoxide in the presence of [BMIM][BF4]. The
      13alpha-16-keto steroid was converted to a mixture of 16-iodo-16-ene and 16-iodo
      15-ene derivatives in two steps by Barton's methodology. Aminocarbonylation of
      the steroidal alkenyl iodides was carried out using different primary and
      secondary amines as nucleophiles. The products, 16-carboxamido-16-ene and 16
      carboxamido-15-ene derivatives, were obtained in good yields and were
      characterized by (1)H and (13)C NMR, IR and MS. The reduction of the above two
      unsaturated carboxamides resulted in the same product, 17alpha-methyl-16alpha
      carboxamido-androstane. 

PMID- 24012727
TI  - The impact of nandrolone decanoate and growth hormone on biosynthesis of steroids
      in rats.
AB  - Growth hormone (GH) and anabolic androgenic steroids (AAS) are commonly used in
      sports communities. Several studies have suggested an association between GH and
      AAS. We have investigated the impact of GH in rats treated with nandrolone
      decanoate (ND). Male Wistar rats received ND (15 mg/kg) every third day during
      three weeks and were subsequently treated with recombinant human GH (1.0I U/kg)
      for ten consecutive days. Plasma samples were collected and peripheral organs
      (i.e. heart, liver, testis and thymus) were dissected and weighed. Concentration
      of thirteen endogenous steroids was measured in the rat plasma samples using high
      specificity LC-MS/MS methods. Seven steroids were detected and quantified, and
      concentrations of estrone, testosterone, and androstenedione were significantly
      different among the groups, while concentrations of pregnenolone, DHEA, 17
      hydroxyprogesterone and corticosterone were not altered. Administration of rhGH
      alone altered the plasma steroid distribution, and the results demonstrated
      significantly increased concentrations of plasma estrone as well as decreased
      concentrations of testosterone and androstenedione in the ND-treated rats.
      Administration of rhGH to ND-pretreated rats did not reverse the alteration of
      the steroid distribution induced by ND. Administration of ND decreased the weight
      of the thymus, and addition of rhGH did not reverse this reduction. However, rhGH
      administration induced an enlargement of thymus. Taken together, the plasma
      steroid profile differed in the four groups, i.e. control, AAS, rhGH and the
      combination of AAS and rhGH treatment.

PMID- 24012728
TI  - Novel nucleotide insertions in two unrelated Indian patients with 5alpha
      reductase 2 deficiency leading to premature termination of SRD5A2 enzyme.
AB  - T is converted to a more potent androgen, DHT by the action of microsomal
      membrane enzyme 5alpha reductase 2. Defects in 5alpha reductase 2 isozyme results
      in incomplete virilisation of external male genitalia. Mutations in SRD5A2 gene
      leads to diminished enzyme activity, thus hampering DHT synthesis from T. We
      describe two unrelated patients from India with 5alphaRD2 due to novel insertion
      of nucleotides in the exon 1 of SRD5A2 gene that lead to premature termination of
      protein. Master S (case 1; III.8) was 3 years old at initial evaluation, had
      perineoscrotal hypospadias, microphallus and both testes were palpable in the
      inguinal region. Master P (case 2; III.9) was born as normal full term baby. He
      had primary complaint of microphallus, penoscrotal hypospadias and gonads in the
      inguinal region. Diagnosis of 5alphaRD2 was made, as T/DHT ratio in the two cases
      was 41 and 131.2 respectively. Sequence analysis of SRD5A2 gene showed an
      insertion of nucleotides TA in exon 1 (c.188_189). This resulted in premature
      termination of the protein due to stop codon at amino acid position 7. The
      protein formed is drastically truncated and inadequate protein synthesized
      explains the phenotypic characteristics of our patients.

PMID- 24012729
TI  - Three new neuritogenic steroidal saponins from Ophiopogon japonicus (Thunb.) Ker
      Gawl.
AB  - Three new steroidal saponins (1-3) and a known saponin (4) were isolated from
      Ophiopogon japonicus (Thunb.) Ker-Gawl. Their structures were determined by
      spectroscopic analyses and chemical derivatization. The isolated compounds (1-4)
      were potent inducers of neuritogenesis on PC12 cells. Compound 1 showed the
      highest neuritogenic activity of 46% at 1 MUM. The study of structure-activity
      relationships suggests that aglycone is important for the neuritogenic activity
      of the compounds. Specific inhibitor experiments and Western blot analysis
      suggest that 1-induced neuritogenic activity depends on the activation of mitogen
      activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK)
      signaling pathway on PC12 cells.

PMID- 24012730
TI  - Liquid chromatography tandem mass spectrometry in study of the pharmacokinetics
      of six steroidal saponins in rats.
AB  - A rapid, simple and sensitive high-performance liquid chromatography tandem mass
      spectrometry method was developed and validated for simultaneous determination of
      six main steroidal saponins in Paris polyphylla in rat plasma. Ginsenoside Rg3
      was selected as the internal standard (IS). Plasma samples were pretreated with
      protein precipitation, and the separation was achieved on a reverse phase Agilent
      poroshell120 EC-C18 column using a gradient mobile phase system of acetonitrile
      water containing 0.1% formic acid. The triple quadruple mass spectrometer was set
      in negative electrospray ionization mode and multiple reaction monitoring (MRM)
      was used for six steroidal saponins quantification. The precursors to produce ion
      transitions monitored for polyphyllin I, polyphyllin II, polyphyllin VI,
      polyphyllin VII, dioscin, gracillin and IS were m/z 899.5>853.4, 1059.5>1013.5,
      783.4>737.4, 1075.5>1029.5, 913.5>867.4, 929.5>883.4 and 819.5>783.4,
      respectively. The intra- and inter-day precisions (RSD%) were less than 13% and
      the average extraction recoveries ranged from 85% to 97.0% for each analyte. Six
      steroidal saponins were proved to be stable during sample storage, preparation
      and analytical procedures. The established method was employed for simultaneous
      quantification and successfully used for the first time for the pharmacokinetics
      evaluation of the six main compounds after intragastric administration of P.
      polyphylla extract in Sprague-Dawley rats. 

PMID- 24012731
TI  - Cytotoxic, pro-apoptotic, pro-oxidant, and non-genotoxic activities of a novel
      copper(II) complex against human cervical cancer.
AB  - Cisplatin remains one of the most effective current chemotherapeutic agents;
      however, metal complexes synthesis has increased in order to produce new anti
      neoplastic drugs with DNA binding and apoptotic activities in tumor cells and
      less toxicity for patients. In this study, we evaluated the cytotoxic activity of
      a novel copper(II) complex (LQM402) against cervical cancer cell lines and found
      that LQM402 exhibited selective cytotoxicity against HeLa and Ca Ski cells. FITC
      annexin assay and DNA fragmentation indicated that apoptosis could be involved in
      HeLa cell death. Caspase 3/7 and cytochrome c analysis by immunoblotting suggest
      the intrinsic pathway. LQM402 is a lipid peroxidation inductor according to TBARS
      production. Additionally, the Ames and micronucleus tests demonstrated non
      genotoxic activity for this compound in Salmonella typhimurium and CD1 mice,
      respectively. Therefore, LQM402 may be a promising and safe anti-cervical cancer
      compound. 

PMID- 24012732
TI  - Relative performance of biofilm configuration over suspended growth operation on
      azo dye based wastewater treatment in periodic discontinuous batch mode
      operation.
AB  - Functional role of biofilm and suspended growth bioreactor configurations in
      response to the treatment of azo-dye (C.I. Acid Black 10B) bearing wastewater was
      evaluated in periodic discontinuous batch mode operation at varying dye
      concentrations. The biofilm system depicted higher dye removal efficiency
      (93.14%) compared to suspended mode (84.29%) at 350 mg dye/l operation. Both the
      reactor configurations did not show much process inhibition at higher dye loads
      studied. Azo reductase and dehydrogenase enzyme activities showed significant
      variation indicating the different metabolic capabilities of the native
      microflora, stable proton shuttling between metabolic intermediates and
      differences in the delivery of reducing powers from the substrate metabolism
      towards dye removal. Voltammograms visualized marked variations in electron
      discharge properties with the function of reactor configuration, time intervals
      and dye load. Higher redox catalytic currents, lower Tafel slopes and
      polarization resistance showed good correlation with enzyme activities and dye
      removal.

PMID- 24012733
TI  - In-situ combination of fermentation and electrodialysis with bipolar membranes
      for the production of lactic acid: continuous operation.
AB  - An experimental study was carried out to achieve a continuous integrated
      operation of fermentation and electrodialysis with bipolar membranes (EDBM).
      There need three steps to accomplish this experiment: (1) individual continuous
      fermentation; (2) individual continuous EDBM; (3) integrated operation of
      fermentation and EDBM under continuous condition. The results indicate that the
      maximum feed rate (fermenter can afford) is 0.24 L/h, which is also equal to the
      feed rate of the subsequent individual continuous EDBM. During continuous EDBM,
      the recovery ratio of lactate from the fermentation broth can reach 69.5% under a
      current density of 40 mA/cm(2). The net end concentration and total molar
      quantity for lactic acid can reach 1.46 mol/L and 2.18 mol, and for OH(-) are
      1.32 mol/L and 1.70 mol, respectively. The integration can be achieved only under
      an initial alkali concentration of no less than 1 mol/L and a current density of
      no less than 30 mA/cm(2).

PMID- 24012734
TI  - Studies on xylitol production by metabolic pathway engineered Debaryomyces
      hansenii.
AB  - Debaryomyces hansenii is one of the most promising natural xylitol producers. As
      the conversion of xylitol to xylulose mediated by NAD(+) cofactor dependent
      xylitol dehydrogenase (XDH) reduces its xylitol yield, xylitol dehydrogenase gene
      (DhXDH)-disrupted mutant of D. hansenii having potential for xylose assimilating
      pathway stopping at xylitol, was used to study the effects of co-substrates,
      xylose and oxygen availability on xylitol production. Compared to low cell growth
      and xylitol production in cultivation medium containing xylose as the only
      substrate, XDH disrupted mutants grown on glycerol as co-substrate accumulated
      2.5-fold increased xylitol concentration over those cells grown on glucose as co
      substrate. The oxygen availability, in terms of volumetric oxygen transfer
      coefficient, kLa (23.86-87.96 h(-1)), affected both xylitol productivity and
      yield, though the effect is more pronounced on the former. The addition of extra
      xylose at different phases of xylitol fermentation did not enhance xylitol
      productivity under experimental conditions.

PMID- 24012735
TI  - Effect of biodiesel addition on microbial community structure in a simulated fuel
      storage system.
AB  - Understanding changes in microbial structure due to biodiesel storage is
      important both for protecting integrity of storage systems and fuel quality
      management. In this work a simulated storage system was used to study the effect
      of biodiesel (0%, 25%, 50%, 75% and 100%) on a microbial population, which was
      followed by community level physiological profiling (CLPP), 16s rDNA analysis and
      plating in selective media. Results proved that structure and functionality were
      affected by biodiesel. CLPP showed at least three populations: one corresponding
      to diesel, one to biodiesel and one to blends of diesel and biodiesel. Analysis
      of 16s rDNA revealed that microbial composition was different for populations
      growing in diesel and biodiesel. Genera identified are known for degradation of
      hydrocarbons and emulsifier production. Maximum growth was obtained in biodiesel;
      however, microbial counts in standard media were lower for this samples.
      Acidification of culture media was observed at high biodiesel concentration. 

PMID- 24012736
TI  - Isolation and characterization of a novel cinosulfuron degrading Kurthia sp. from
      a methanogenic microbial consortium.
AB  - A novel bacterial strain LAM0713 was isolated from a methanogenic bacterial
      complexes and identified as Kurthia sp. based on morphological, cultural, physio
      biochemical characteristics and analysis of 16S rDNA sequence. Strain LAM0713 was
      found to be capable of utilizing cinosulfuron as sole nitrogen source for growth
      over a wide range of temperature (20-40  degrees C) and pH (5.0-9.0). Response
      surface methodology was used to optimize the degradation conditions. Strain
      LAM0713 could efficiently degrade 92.4% of initially supplemented 50 mg.L(1)
      cinosulfuron under the optimum conditions (pH 6.9, 31.8  degrees C) within 5
      days. Five intermediates formed during cinosulfuron degradation were detected by
      liquid chromatography mass spectrometry (LC-MS), and a metabolic pathway for
      cinosulfuron degradation was proposed via cleavage of the sulfonylurea bridge. It
      is the first report showing that Kurthia sp. strain could degrade sulfonylurea
      herbicides, suggesting that strain LAM0713 may provide new insight into microbial
      degradation of herbicides.

PMID- 24012737
TI  - Nutrient deprivation enhances lipid content in marine microalgae.
AB  - The lipid content of microalgae is important for biodiesel production. In this
      study, we determined photosynthetic performance, biomass composition and lipid
      production of marine unicellular microalgae Chaetoceros muelleri
      (Bacillariophyceae) and Dunaliella salina (Chlorophyceae) cultured under
      different nutrient deprivation conditions. The results showed the highest lipid
      content of C. muelleri (46.32+/-3.53%) and D. salina (54.15+/-2.71%) could be
      achieved by nitrogen and complete nutrient deprivation, respectively. Analysis of
      fatty acid methyl esters (FAMEs) profile under those conditions revealed that the
      lipid accumulated by the two species was suitable to produce biodiesel. From
      these studies, we concluded that C. muelleri and D. salina would be highly
      suitable candidates for biodiesel production. 

PMID- 24012738
TI  - Enhancement of lipid production in low-starch mutants Chlamydomonas reinhardtii
      by adaptive laboratory evolution.
AB  - Adaptive laboratory evolution (ALE) is an effective method to improve microalgal
      strains. The growth phenotypes of three strains (cc4324, cc4326 and cc4334) of
      green microalgae Chlamydomonas reinhardtii were enhanced by ALE. As a result,
      endpoint strains exhibited higher growth rates. Upon the utilisation of ALE
      strategy, the biomass concentrations of the endpoint strains of cc4324, cc4326
      and cc4334 became 1.17, 1.33 and 1.48 times of those of the starting strains. The
      total lipid content of the original strains was increased gradually from 32% to
      36.67% in the endpoint strain cc4326 and abruptly increased from 24.27% to 44.67%
      in the endpoint strain cc4334 by nitrogen starvation. Slight growth impairment
      was also observed in low-starch mutants exposed to nitrogen starvation stress.
      However, this impairment was quickly resolved after nitrogen was replenished.
      These findings demonstrated that the biomass concentration and lipid productivity
      of low-starch mutants can be enhanced by ALE. 

PMID- 24012739
TI  - The Knoevenagel reactions of pregnenolone with cyanomethylene reagents: synthesis
      of thiophene, thieno[2,3-b]pyridine, thieno[3,2-d]isoxazole derivatives of
      pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines.
AB  - The reaction of pregnenolone with either 2-aminoprop-1-ene-1,1,3-tricarbonitrile
      or 3-oxo-3-phenylpropanenitrile gave the Knoevenagel condensation products 3 and
      6, respectively. Separation of the E and Z isomeric compounds of 3 and 6 together
      with their structure elucidation were carried out. Some chemical transformations
      of the latter products were carried out and the cytotoxicity of the newly
      obtained products was evaluated against some cancer cell lines and a human normal
      cell line. The results indicated that compounds 15, 17a, 18 and 20e among the
      tested compounds showed the highest cytotoxicity against the cancer cell lines. 

PMID- 24012740
TI  - Invalidation of a commercially available human 5alpha-dihydrotestosterone
      immunoassay.
AB  - Enzyme immunoassays (EIA) are commonly utilized for the evaluation of androgens
      in biological fluids; however, careful consideration must be given to cross
      reactivity with other endogenous sex-steroid hormones. Our purpose was to
      determine the validity of a commonly-utilized commercially-available
      dihydrotestosterone (DHT) EIA. Serum samples obtained from older hypogonadal men
      who participated in a 12-month randomized controlled trial evaluating the effects
      of testosterone-enanthate (125 mg/week) or vehicle in combination with
      finasteride (5mg/day) or placebo were assayed for DHT via EIA and using a
      validated gold-standard LC-MS/MS approach. Additionally, commercially-available
      (DHT-free) buffer containing graded testosterone doses was evaluated by DHT
      immunoassay. DHT concentrations measured via EIA were 79% to >1000% higher than
      values obtained by LC-MS/MS (p<0.05), with the largest differences (415-1128%)
      occuring in groups receiving finasteride. Both LC-MS/MS and EIA indicated that
      testosterone-enanthate increased serum DHT to a similar magnitude. In contrast,
      finasteride-induced reductions in DHT were detected by LC-MS/MS, but not EIA
      (p<0.05). No significant associations were present for DHT concentrations between
      measurement techniques. Cross-reactivity of testosterone with the immunoassay
      ranged from 18% to 99% and DHT concentrations measured by EIA were highly
      associated with the spiked testosterone concentrations in DHT-free buffer
      (r=0.885, p<0.001). In conclusion, we provide evidence invalidating a commonly
      utilized commercially-available DHT immunoassay because significant cross
      reactivity exists between testosterone and the EIA and because the changes in DHT
      observed via EIA were not associated with a validated gold-standard measurement
      technique. The cross-reactivity of testosterone is particularly concerning
      because testsoterone is present in 100-fold greater concentrations than is DHT
      within the circulation.

PMID- 24012741
TI  - Novel recurrent neural network for modelling biological networks: oscillatory p53
      interaction dynamics.
AB  - Understanding the control of cellular networks consisting of gene and protein
      interactions and their emergent properties is a central activity of Systems
      Biology research. For this, continuous, discrete, hybrid, and stochastic methods
      have been proposed. Currently, the most common approach to modelling accurate
      temporal dynamics of networks is ordinary differential equations (ODE). However,
      critical limitations of ODE models are difficulty in kinetic parameter estimation
      and numerical solution of a large number of equations, making them more suited to
      smaller systems. In this article, we introduce a novel recurrent artificial
      neural network (RNN) that addresses above limitations and produces a continuous
      model that easily estimates parameters from data, can handle a large number of
      molecular interactions and quantifies temporal dynamics and emergent systems
      properties. This RNN is based on a system of ODEs representing molecular
      interactions in a signalling network. Each neuron represents concentration change
      of one molecule represented by an ODE. Weights of the RNN correspond to kinetic
      parameters in the system and can be adjusted incrementally during network
      training. The method is applied to the p53-Mdm2 oscillation system - a crucial
      component of the DNA damage response pathways activated by a damage signal.
      Simulation results indicate that the proposed RNN can successfully represent the
      behaviour of the p53-Mdm2 oscillation system and solve the parameter estimation
      problem with high accuracy. Furthermore, we presented a modified form of the RNN
      that estimates parameters and captures systems dynamics from sparse data
      collected over relatively large time steps. We also investigate the robustness of
      the p53-Mdm2 system using the trained RNN under various levels of parameter
      perturbation to gain a greater understanding of the control of the p53-Mdm2
      system. Its outcomes on robustness are consistent with the current biological
      knowledge of this system. As more quantitative data become available on
      individual proteins, the RNN would be able to refine parameter estimation and
      mapping of temporal dynamics of individual signalling molecules as well as
      signalling networks as a system. Moreover, RNN can be used to modularise large
      signalling networks. 

PMID- 24012742
TI  - Immunohistochemical localization of oxytocin receptors in human brain.
AB  - The neuropeptide oxytocin (OT) regulates rodent, primate and human social
      behaviors and stress responses. OT binding studies employing (125)I-d(CH2)5
      [Tyr(Me)2,Thr4,Tyr-NH2(9)] ornithine vasotocin ((125)I-OTA), has been used to
      locate and quantify OT receptors (OTRs) in numerous areas of the rat brain. This
      ligand has also been applied to locating OTRs in the human brain. The results of
      the latter studies, however, have been brought into question because of
      subsequent evidence that (125)I-OTA is much less selective for OTR vs.
      vasopressin receptors in the primate brain. Previously we used a monoclonal
      antibody directed toward a region of the human OTR to demonstrate selective
      immunostaining of cell bodies and fibers in the preoptic-anterior hypothalamic
      area and ventral septum of a cynomolgus monkey (Boccia et al., 2001). The present
      study employed the same monoclonal antibody to study the location of OTRs in
      tissue blocks containing cortical, limbic and brainstem areas dissected from
      fixed adult, human female brains. OTRs were visualized in discrete cell bodies
      and/or fibers in the central and basolateral regions of the amygdala, medial
      preoptic area (MPOA), anterior and ventromedial hypothalamus, olfactory nucleus,
      vertical limb of the diagonal band, ventrolateral septum, anterior cingulate and
      hypoglossal and solitary nuclei. OTR staining was not observed in the hippocampus
      (including CA2 and CA3), parietal cortex, raphe nucleus, nucleus ambiguus or
      pons. These results suggest that there are some similarities, but also important
      differences, in the locations of OTRs in human and rodent brains.
      Immunohistochemistry (IHC) utilizing a monoclonal antibody provides specific
      localization of OTRs in the human brain and thereby provides opportunity to
      further study OTR in human development and psychiatric conditions.

PMID- 24012743
TI  - Targeting the neural extracellular matrix in neurological disorders.
AB  - The extracellular matrix (ECM) is known to regulate important processes in
      neuronal cell development, activity and growth. It is associated with the
      structural stabilization of neuronal processes and synaptic contacts during the
      maturation of the central nervous system. The remodeling of the ECM during both
      development and after central nervous system injury has been shown to affect
      neuronal guidance, synaptic plasticity and their regenerative responses.
      Particular interest has focused on the inhibitory role of chondroitin sulfate
      proteoglycans (CSPGs) and their formation into dense lattice-like structures,
      termed perineuronal nets (PNNs), which enwrap sub-populations of neurons and
      restrict plasticity. Recent studies in mammalian systems have implicated CSPGs
      and PNNs in regulating and restricting structural plasticity. The enzymatic
      degradation of CSPGs or destabilization of PNNs has been shown to enhance
      neuronal activity and plasticity after central nervous system injury. This review
      focuses on the role of the ECM, CSPGs and PNNs; and how developmental and
      pharmacological manipulation of these structures have enhanced neuronal
      plasticity and aided functional recovery in regeneration, stroke, and amblyopia.
      In addition to CSPGs, this review also points to the functions and potential
      therapeutic value of these and several other key ECM molecules in epileptogenesis
      and dementia.

PMID- 24012744
TI  - Regulation of alpha3-containing GABAA receptors in guinea-pig adrenal medullary
      cells by adrenal steroids.
AB  - GABA is thought to function as a paracrine factor in adrenal medullary (AM)
      cells. Thus, we electrophysiologically and immunologically examined the
      properties of GABAA receptors (GABAARs) in guinea-pig AM cells. Bath application
      of GABA produced an inward current at -60 mV in a dose-dependent manner with an
      EC50 of 32.3 MUM. This GABA-induced current was enhanced by allopregnanolone at
      concentrations of 0.01 MUM and more. A prior exposure to allopregnanolone
      resulted in a decrease in an EC50 for GABA in activating GABAARs. The GABA
      induced current was suppressed by Zn(2+) in a dose-dependent manner with an IC50
      of 18 MUM, whereas it was enhanced by 100 MUM La(3+). The benzodiazepine analog
      diazepam was three times more potent than zolpidem in enhancing the GABA current,
      and it was also augmented by L-838,417, which has no action on alpha1-containing
      GABAARs. The GABAAR alpha3, but not alpha1, and gamma2 subunits were
      immunologically detected at the cell periphery. The expression of alpha3 subunits
      in PC12 cells was enhanced by glucocorticoid activity. The results indicated that
      GABAARs in guinea-pig AM cells mainly comprise alpha3, beta, and gamma2 subunits
      and are enhanced by allopreganalone and glucocorticoids may play a major role in
      the expression of alpha3 subunits.

PMID- 24012745
TI  - Olfacto-retinalis pathway in Austrolebias charrua fishes: a neuronal tracer
      study.
AB  - The olfacto-retinal centrifugal system, a constant component of the central
      nervous system that appears to exist in all vertebrate groups, is part of the
      terminal nerve (TN) complex. TN allows the integration of different sensory
      modalities, and its anatomic variability may have functional and evolutionary
      significance. We propose that the olfacto-retinal branch of TN is an important
      anatomical link that allows the functional interaction between olfactory and
      visual systems in Austrolebias. By injecting three different neuronal tracers
      (biocytin, horseradish peroxidase, and 1,1'-dioctadecyl-3,3,3',3'tetramethyl
      indocarbocyanine perchlorate (DiI)) in the left eye of Austrolebias charrua
      fishes, we identified the olfacto-retinal branch of TN and related neuronal somas
      that were differentiable by location, shape, and size. The olfacto-retinal TN
      branch is composed of numerous thin axons that run ventrally along the olfactory
      bulb (OB) and telencephalic lobes, and appears to originate from a group of many
      small monopolar neurons located in the rostral portion of both the ipsi- and
      contralateral OB (referred to as region 1). Labeled cells were found in two other
      regions: bipolar and multipolar neurons in the transition between the OB and
      telencephalic lobes (region 2) and two other groups in the preoptic/pretectal
      area (region 3). In this last region, the most rostral group is constituted by
      monopolar pear-shaped neurons and may belong to the septo-preoptic TN complex.
      The second group, putatively located in the pretectal region, is formed by
      pseudounipolar neurons and coincides with a conserved vertebrate nucleus of the
      centrifugal retinal system not involved in the TN complex. The found that
      connections between the olfactory and visual systems via the olfacto-retinal TN
      branch suggest an early interaction between these sensory modalities, and
      contribute to the identification of their currently unknown circuital
      organization.

PMID- 24012746
TI  - PI3Kgamma inhibition alleviates symptoms and increases axon number in
      experimental autoimmune encephalomyelitis mice.
AB  - Phosphoinositide 3-kinase gamma (PI3Kgamma) is a shared downstream component of
      chemokine-mediated signaling pathways and regulates migration, proliferation and
      activation of inflammatory cells. PI3Kgamma has been shown to play a crucial role
      in regulating inflammatory responses during the progression of several diseases.
      We investigated the potential function of PI3Kgamma in mediating inflammatory
      reactions and the development of experimental autoimmune encephalomyelitis (EAE),
      a model of multiple sclerosis (MS). We found that systemic treatment with
      selective PI3Kgamma inhibitor AS-604850 significantly reduced the number of
      infiltrated leukocytes in the CNS and ameliorated the clinical symptoms of EAE
      mice. Treatment with this PI3Kgamma inhibitor enhanced myelination and axon
      number in the spinal cord of EAE mice. Consistently, we demonstrated that
      PI3Kgamma deletion in knockout mice mitigates the clinical sign of EAE compared
      to PI3Kgamma+/+ controls. PI3Kgamma deletion increased the number of axons in the
      lumbar spinal cord, including descending 5-HT-positive serotonergic fiber tracts.
      Our results indicate that PI3Kgamma contributes to development of autoimmune CNS
      inflammation and that PI3Kgamma blockade may provide a great potential for
      treating patients with MS.

PMID- 24012747
TI  - Loss of functional Dicer in mouse radial glia cell-autonomously prolongs cortical
      neurogenesis.
AB  - Radial glia of the mouse cerebral cortex emerge from neuroepithelial stem cells
      around embryonic day 11 and produce excitatory cortical neurons until a few days
      before birth. The molecular mechanisms that regulate the end of cortical
      neurogenesis remain largely unknown. Here we investigated if the Dicer-dependent
      microRNA (miRNA) pathway is involved. By electroporating a cre-recombinase
      expression vector into the cortex of E13.5 embryos carrying a conditional allele
      of Dicer1, we induced mosaic recombination causing Dicer1 deletion and reporter
      activation in a subset of radial glia. We analysed the long-term fates of their
      progeny. We found that mutant radial glia produced abnormally large numbers of
      Cux1-positive neurons, many of which populated the superficial cortical layers.
      Injections of the S-phase marker bromodeoxyuridine between postnatal days 3 and
      14 showed that much of this population was generated postnatally. Our findings
      suggest a role for Dicer-dependent processes in limiting the timespan of cortical
      neurogenesis. 

PMID- 24012748
TI  - Piscidins in the intestine of European perch, Perca fluviatilis, naturally
      infected with an enteric worm.
AB  - This study set out to determine how an enteric parasite, the thorny-headed worm
      Acanthocephalus lucii, affected the expression of antimicrobial peptides
      (piscidins) in its host population, the European perch (Perca fluviatilis)
      collected from Lake Piediluco in Central Italy. A total of 87 perch were
      examined; 44 (50.5%) were infected with A. lucii (1-18 worms fish(-1)).
      Pathological changes and immune response were assessed using histological,
      ultrastructural and immunohistochemical techniques. The acanthocephalans only
      penetrated the surficial zone of the intestinal wall and induced only slight
      inflammation. The main damage was destruction of the mucosal epithelium covering
      the villi adjacent to the parasite's attachment site, and included necrosis and
      degeneration. Infected intestine had numerous mast cells (MCs), often in close
      proximity to, and within, the capillaries, and were associated with fibroblasts
      of the submucosal layer. Mast cells were irregular in shape with a cytoplasm
      filled by numerous electron-dense, membrane-bounded granules. Immunostaining of
      intestine with antibodies against the antimicrobial peptides piscidin 3 and
      piscidin 4 showed subpopulations of MCs that were positive. Piscidin-positive MCs
      were mainly observed among the epithelial cells of the intestine, but also within
      the submucosa. In both uninfected and parasite-infected perch, the number of MCs
      positive for piscidin 4 was higher than those immunoreactive with piscidin 3 (p <
      0.05). For both piscidins, there was no significant difference in the number of
      positive MCs between parasite-infected and uninfected intestine (p > 0.05).
      However, uninfected fish showed higher immunostaining intensity for piscidin 3
      than infected conspecifics (p < 0.05).

PMID- 24012750
TI  - SmCCL19, a CC chemokine of turbot Scophthalmus maximus, induces leukocyte
      trafficking and promotes anti-viral and anti-bacterial defense.
AB  - Chemokines are classified into several different subfamilies, of which CC
      chemokines constitute the largest subfamily in teleost. The prominent structural
      characteristic of CC chemokines is the presence of an Asp-Cys-Cys-Leu (DCCL)
      motif. To date, cDNA sequences of several CC chemokines have been identified in
      turbot (Scophthalmus maximus), however, the activity and function of these
      putative chemokines remain unknown. In this study, we examined the biological
      effect of the turbot CC chemokine SmCCL19, which has been previously reported as
      KC70 and shown to be regulated in expression by bacterial infection. To
      facilitate functional analysis, recombinant SmCCL19 (rSmCCL19) and a mutant form
      of SmCCL19, SmCCL19M, that bears serine substitutions at the two cysteine
      residues of the DCCL motif were purified from Escherichia coli. Chemotactic
      analysis showed that rSmCCL19 induced migration of head kidney leukocytes in a
      dose-dependent manner, whereas rSmCCL19M caused no apparent cellular migration.
      To examine the in vivo effect of rSmCCL19, turbot were administered with rSmCCL19
      or rSmCCL19M before being inoculated with viral and bacterial pathogens.
      Subsequent tissue infection analysis showed that the viral and bacterial loads in
      rSmCCL19-adminsitered fish were significantly reduced, whereas the pathogen loads
      in rSmCCL19M-adminsitered fish were largely comparable to those in the control
      fish. Consistent with these observations, significant inductions of immune
      relevant genes were observed in rSmCCL19-adminsitered fish but not in rSmCCL19M
      adminsitered fish. Taken together, these results indicate that SmCCL19 recruits
      leukocytes and augments host immune defense in a manner that depends on the
      conserved DCCL motif.

PMID- 24012749
TI  - A novel C-type lectin from Eriocheir sinensis functions as a pattern recognition
      receptor with antibacterial activity.
AB  - As pattern recognition receptors (PRRs), C-type lectins (CTLs) play significant
      roles in recognizing and eliminating pathogens in innate immunity. In this study,
      a novel CTL (EsLecD) was identified from the crustacean Eriocheir sinensis. The
      cloning of full-length EsLecD cDNA was based on the initial expressed sequence
      tags (ESTs) isolated from a hepatopancreatic cDNA library. The full-length EsLecD
      cDNA of 686 bp with an open reading frame of 468 bp encodes a putative protein of
      155 aa residues, including an N-terminal signal peptide and a single carbohydrate
      recognition domain (CRD). By quantitative RT-PCR analysis, the EsLecD transcript
      was mainly detected in the hepatopancreas but rarely in other tissues, and it was
      significantly upregulated in the hepatopancreas after immune challenge with
      lipopolysaccharides. The recombinant EsLecD protein (rEsLecD) exhibited the
      ability to bind to all tested microorganisms, including bacteria and yeast.
      Meanwhile, calcium significantly increased the binding affinity of rEsLecD toward
      microorganisms, but it was not essential. The binding of rEsLecD induced the
      aggregation of microbial pathogens. Moreover, rEsLecD was capable of inhibiting
      the growth of microorganisms and even directly killing bacteria. Interestingly,
      rEsLecD could stimulate cellular encapsulation in vitro. In conclusion, results
      of this study suggest that EsLecD acts as an antibacterial PRR participating in
      the innate immunity of invertebrates.

PMID- 24012751
TI  - Molecular cloning, characterization and expression analysis of tumor suppressor
      protein p53 from orange-spotted grouper, Epinephelus coioides in response to
      temperature stress.
AB  - The tumor suppressor protein p53 is a critical component of cell cycle checkpoint
      responses. It upregulates the expression of cyclin-dependent kinase inhibitors in
      response to DNA damage and other cellular perturbations, and promotes apoptosis
      when DNA repair pathways are overwhelmed. In the present study, the cDNA of p53
      from the orange-spotted grouper (Epinephelus coioides) (Ec-p53) was cloned by the
      combination of homology cloning and rapid amplification of cDNA ends (RACE)
      approaches. The full-length cDNA of Ec-p53 was of 1921 bp, including an open
      reading frame (ORF) of 1143 bp encoding a polypeptide of 380 amino acids with
      predicted molecular weight of 42.3 kDa and theoretical isoelectric point of 7.0.
      Quantitative real-time PCR (qRT-PCR) assays revealed that Ec-p53 was ubiquitously
      expressed in all the examined tissues but with high levels in intestine and liver
      of the orange-spotted grouper. In addition, we measured the DNA damage and
      apoptosis in the blood cells and the percentage of dead and damaged blood cells.
      Our results suggest that oxidative stress and DNA damage occurred in grouper in
      conditions where the temperature was 15 +/- 0.5  degrees C. Furthermore, qRT-PCR
      and western blot confirmed that low temperature stress induced upregulation of Ec
      p53 in the mRNA and protein levels. These results suggest that low temperature
      induced oxidative stress may cause DNA damage or apoptosis, and cooperatively
      stimulate the expression of Ec-p53, which plays a critical role in immune defense
      and antioxidant responses.

PMID- 24012752
TI  - Evidences of SNPs in the variable region of hemocyanin Ig-like domain in shrimp
      Litopenaeus vannamei.
AB  - Single nucleotide polymorphisms (SNPs) are the commonest mode of genetic
      variation in invertebrate immune-related genes. Hemocyanin presents in the
      hemolymph of both mollusks and arthropods and functions as an important antigen
      non-specific immune protein. But people know very little about its gene
      polymorphism so far. In current study, bioinformatics, molecular biology and
      environmental challenge approaches were used to identify the SNPs within
      hemocyanin Ig-like domain in shrimp Litopenaeus vannamei. A total of 11 SNPs were
      found in a variable region of Ig-like domain from L. vannamei hemocyanin large
      subunit (1258-1460 bp, HcLV1), 5 of which (1272, 1315, 1380, 1410 and 1450) were
      confirmed present in both genomic DNA and cDNA by clone sequencing. Furthermore,
      HcLV1 showed 3, 5 and 5 SSCP bands, respectively, in 16, 25 and 30  degrees C
      treated shrimps, suggesting that the SSCP pattern of HcLV1 could be modulated by
      environmental stress. In addition, HcLV1 displayed two extra bands with different
      mobility when shrimps treated with Vibrio parahaemolyticus for 6-24 h, which was
      not observed in the control group. In conclusion, our data suggest that shrimp L.
      vannamei hemocyanin Ig-like domain possesses SNPs, which may be associated with
      environmental stress or pathogenic challenge.

PMID- 24012753
TI  - Endothelial Jagged-1 is necessary for homeostatic and regenerative hematopoiesis.
AB  - The bone marrow (BM) microenvironment is composed of multiple niche cells that,
      by producing paracrine factors, maintain and regenerate the hematopoietic stem
      cell (HSC) pool (Morrison and Spradling, 2008). We have previously demonstrated
      that endothelial cells support the proper regeneration of the hematopoietic
      system following myeloablation (Butler et al., 2010; Hooper et al., 2009;
      Kobayashi et al., 2010). Here, we demonstrate that expression of the angiocrine
      factor Jagged-1, supplied by the BM vascular niche, regulates homeostatic and
      regenerative hematopoiesis through a Notch-dependent mechanism. Conditional
      deletion of Jagged-1 in endothelial cells (Jag1((ECKO)) mice) results in a
      profound decrease in hematopoiesis and premature exhaustion of the adult HSC
      pool, whereas quantification and functional assays demonstrate that loss of
      Jagged-1 does not perturb vascular or mesenchymal compartments. Taken together,
      these data demonstrate that the instructive function of endothelial-specific
      Jagged-1 is required to support the self-renewal and regenerative capacity of
      HSCs in the adult BM vascular niche.

PMID- 24012754
TI  - DREADDs in Drosophila: a pharmacogenetic approach for controlling behavior,
      neuronal signaling, and physiology in the fly.
AB  - We have translated a powerful genetic tool, designer receptors exclusively
      activated by designer drugs (DREADDs), from mammalian systems to Drosophila
      melanogaster to selectively, rapidly, reversibly, and dose-dependently control
      behaviors and physiological processes in the fly. DREADDs are muscarinic
      acetylcholine G protein-coupled receptors evolved for loss of affinity to
      acetylcholine and for the ability to be fully activated by an otherwise
      biologically inert chemical, clozapine-N-oxide. We demonstrate its ability to
      control a variety of behaviors and processes in larvae and adults, including
      heart rate, sensory processing, diurnal behavior, learning and memory, and
      courtship. The advantages of this particular technology include the dose
      responsive control of behaviors, the lack of a need for specialized equipment,
      and the capacity to remotely control signaling in essentially all neuronal and
      nonneuronal fly tissues. 

PMID- 24012755
TI  - SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases
      with telomeres.
AB  - SLX4 interacts with several endonucleases to resolve structural barriers in DNA
      metabolism. SLX4 also interacts with telomeric protein TRF2 in human cells. The
      molecular mechanism of these interactions at telomeres remains unknown. Here, we
      report the crystal structure of the TRF2-binding motif of SLX4 (SLX4TBM) in
      complex with the TRFH domain of TRF2 (TRF2TRFH) and map the interactions of SLX4
      with endonucleases SLX1, XPF, and MUS81. TRF2 recognizes a unique HxLxP motif on
      SLX4 via the peptide-binding site in its TRFH domain. Telomeric localization of
      SLX4 and associated nucleases depend on the SLX4-endonuclease and SLX4-TRF2
      interactions and the protein levels of SLX4 and TRF2. SLX4 assembles an
      endonuclease toolkit that negatively regulates telomere length via SLX1-catalyzed
      nucleolytic resolution of telomere DNA structures. We propose that the SLX4-TRF2
      complex serves as a double-layer scaffold bridging multiple endonucleases with
      telomeres for recombination-based telomere maintenance. 

PMID- 24012756
TI  - Golgi protein ACBD3 mediates neurotoxicity associated with Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal-dominant neurodegenerative disease
      caused by the expansion of polyglutamine repeats in the gene for huntingtin
      (Htt). In HD, the corpus striatum selectively degenerates despite the uniform
      expression of mutant huntingtin (mHtt) throughout the brain and body. Striatal
      selectivity reflects the binding of the striatal-selective protein Rhes to mHtt
      to augment cytotoxicity, but molecular mechanisms underlying the toxicity have
      been elusive. Here, we report that the Golgi protein acyl-CoA binding domain
      containing 3 (ACBD3) mediates mHtt cytotoxicity via a Rhes/mHtt/ACBD3 complex.
      ACBD3 levels are markedly elevated in the striatum of HD patients, in a striatal
      cell line harboring polyglutamine repeats, and in the brains of HD mice.
      Moreover, ACBD3 deletion abolishes HD neurotoxicity, which is increased by ACBD3
      overexpression. Enhanced levels of ACBD3 elicited by endoplasmic reticulum,
      mitochondrial, and Golgi stresses may account for HD-associated augmentation of
      ACBD3 and neurodegeneration. 

PMID- 24012758
TI  - Multiple regulatory layers of SREBP1/2 by SIRT6.
AB  - The NAD(+)-dependent protein deacetylase SIRT6 regulates genome stability,
      cancer, and lifespan. Mice overexpressing SIRT6 (MOSES) have lower low-density
      lipoprotein cholesterol levels and are protected against the physiological damage
      of obesity. Here, we examined the role of SIRT6 in cholesterol regulation via the
      lipogenic transcription factors SREBP1 and SREBP2, and AMP-activated protein
      kinase (AMPK). We show that SIRT6 represses SREBP1 and SREBP2 by at least three
      mechanisms. First, SIRT6 represses the transcription levels of SREBP1/SREBP2 and
      that of their target genes. Second, SIRT6 inhibits the cleavage of SREBP1/SREBP2
      into their active forms. Third, SIRT6 activates AMPK by increasing the AMP/ATP
      ratio, which promotes phosphorylation and inhibition of SREBP1 by AMPK.
      Reciprocally, the expression of miR33a and miR33b from the introns of SREBP2 and
      SREBP1, respectively, represses SIRT6 levels. Together, these findings explain
      the mechanism underlying the improved cholesterol homeostasis in MOSES mice,
      revealing a relationship between fat metabolism and longevity. 

PMID- 24012757
TI  - Selective small molecule targeting beta-catenin function discovered by in vivo
      chemical genetic screen.
AB  - The canonical Wnt signaling pathway, mediated by the transcription factor beta
      catenin, plays critical roles in embryonic development and represents an
      important therapeutic target. In a zebrafish-based in vivo screen for small
      molecules that specifically perturb embryonic dorsoventral patterning, we
      discovered a compound named windorphen that selectively blocks the Wnt signal
      required for ventral development. Windorphen exhibits remarkable specificity
      toward beta-catenin-1 function, indicating that the two beta-catenin isoforms
      found in zebrafish are not functionally redundant. We show that windorphen is a
      selective inhibitor of p300 histone acetyltransferase, a coactivator that
      associates with beta-catenin. Finally, windorphen robustly and selectively kills
      cancer cells that harbor Wnt-activating mutations, supporting the therapeutic
      potential of this Wnt inhibitor class.

PMID- 24012759
TI  - Insulin biosynthetic interaction network component, TMEM24, facilitates insulin
      reserve pool release.
AB  - Insulin homeostasis in pancreatic beta cells is now recognized as a critical
      element in the progression of obesity and type II diabetes (T2D). Proteins that
      interact with insulin to direct its sequential synthesis, folding, trafficking,
      and packaging into reserve granules in order to manage release in response to
      elevated glucose remain largely unknown. Using a conformation-based approach
      combined with mass spectrometry, we have generated the insulin biosynthetic
      interaction network (insulin BIN), a proteomic roadmap in the beta cell that
      describes the sequential interacting partners of insulin along the secretory
      axis. The insulin BIN revealed an abundant C2 domain-containing transmembrane
      protein 24 (TMEM24) that manages glucose-stimulated insulin secretion from a
      reserve pool of granules, a critical event impaired in patients with T2D. The
      identification of TMEM24 in the context of a comprehensive set of sequential
      insulin-binding partners provides a molecular description of the insulin
      secretory pathway in beta cells.

PMID- 24012760
TI  - The RNA methyltransferase Dnmt2 is required for efficient Dicer-2-dependent siRNA
      pathway activity in Drosophila.
AB  - Transfer RNA (tRNA) fragmentation in response to stress conditions has been
      described in many organisms. tRNA fragments have been found in association with
      small interfering RNA (siRNA) components, but the biological role of these
      interactions remains unclear. We report here that the tRNA methyltransferase
      Dnmt2 is essential for efficient Dicer-2 (Dcr-2) function in Drosophila. Using
      small RNA (sRNA) sequencing, we confirmed that Dnmt2 limits the extent of tRNA
      fragmentation during the heat-shock response. tRNAs as well as tRNA fragments
      serve as Dcr-2 substrates, and Dcr-2 degrades tRNA-derived sequences, especially
      under heat-shock conditions. tRNA-derived RNAs are able to inhibit Dcr-2 activity
      on long double-stranded RNAs (dsRNAs). Consequently, heat-shocked Dnmt2 mutant
      animals accumulate dsRNAs, produce fewer siRNAs, and show misregulation of siRNA
      pathway-dependent genes. These results reveal the impact of tRNA fragmentation on
      siRNA pathways and implicate tRNA modifications in the regulation of sRNA
      homeostasis during the heat-shock response. 

PMID- 24012761
TI  - Differential translation tunes uneven production of operon-encoded proteins.
AB  - Clustering of functionally related genes in operons allows for coregulated gene
      expression in prokaryotes. This is advantageous when equal amounts of gene
      products are required. Production of protein complexes with an uneven
      stoichiometry, however, requires tuning mechanisms to generate subunits in
      appropriate relative quantities. Using comparative genomic analysis, we show that
      differential translation is a key determinant of modulated expression of genes
      clustered in operons and that codon bias generally is the best in silico
      indicator of unequal protein production. Variable ribosome density profiles of
      polycistronic transcripts correlate strongly with differential translation
      patterns. In addition, we provide experimental evidence that de novo initiation
      of translation can occur at intercistronic sites, allowing for differential
      translation of any gene irrespective of its position on a polycistronic
      messenger. Thus, modulation of translation efficiency appears to be a universal
      mode of control in bacteria and archaea that allows for differential production
      of operon-encoded proteins.

PMID- 24012762
TI  - NLRP3 inflammasome blockade inhibits VEGF-A-induced age-related macular
      degeneration.
AB  - The NLRP3 inflammasome is activated in age-related macular degeneration (AMD),
      but it remains unknown whether its activation contributes to AMD pathologies.
      VEGF-A is increased in neovascular ("wet") AMD, but it is not known whether it
      plays a role in inflammasome activation, whether an increase of VEGF-A by itself
      is sufficient to cause neovascular AMD and whether it can contribute to
      nonexudative ("dry") AMD that often co-occurs with the neovascular form. Here, it
      is shown that an increase in VEGF-A results in NLRP3 inflammasome activation and
      is sufficient to cause both forms of AMD pathologies. Targeting NLRP3 or the
      inflammasome effector cytokine IL-1beta inhibits but does not prevent VEGF-A
      induced AMD pathologies, whereas targeting IL-18 promotes AMD. Thus, increased
      VEGF-A provides a unifying pathomechanism for both forms of AMD; combining
      therapeutic inhibition of both VEGF-A and IL-1beta or the NLRP3 inflammasome is
      therefore likely to suppress both forms of AMD. 

PMID- 24012763
TI  - Microfluidic immunodetection of cancer cells via site-specific microcontact
      printing of antibodies on nanoporous surface.
AB  - We demonstrate an efficient method for cancer cell capture via cell line-specific
      protein deposition on nanoporous surface in microfluidic channels. Specifically,
      anti-epithelial cell adhesion molecules (EpCAM) were microcontact printed onto
      nanoporous silica substrate with optimal pore size of 4 nm, porosity of 52.4 +/-
      0.2%, and thin film thickness of 130 +/- 0.5 nm. SkBr3, Colo205, and MDA-MB-435
      cancer cells suspended in buffer solution were captured on the stamped nanoporous
      silica substrate. The method demonstrated significantly higher numbers of
      captured EpCAM-positive cancer cells within anti-EpCAM stamped areas. For site
      selective cell capture, grooved microfluidic channels were designed to
      investigate effects of local confinement due to the laminar flows. Both
      theoretical modeling and experiments show that the integration of the
      microfluidic channels greatly enhances cell capture. Patterning of anti-EpCAM in
      areas of downward flow (optimal regions for cell capture), generated by grooves
      of the microchannel, enables higher capture numbers than that of stamped areas of
      upward flow (non-optimal). Fluorescence microscopy images were acquired for
      captured SkBr3 and Colo205 cells using anti-EpCAM on the nanoporous silica
      substrate. It was shown that higher numbers of cells were captured across all
      EpCAM-positive cell lines in optimal areas versus non-optimal areas. Spatial
      control and large scale patterning of proteins enable novel designs and
      productions of cost effective, high throughput, and integrated detection and
      analysis systems. Site-selective detection provides the capability of defining
      optimal locations for cell capture based on various channel geometries and flow
      profile. The demonstrated method shows great potential for point-of-care cancer
      diagnostic tools to quantify the progression and status of the disease.

PMID- 24012764
TI  - Stable and selective scintillating anion-exchange sensors for quantification of
      99TcO4- in natural freshwaters.
AB  - New dual functionality scintillating anion-exchange resins were developed for
      selective determination of (99)TcO4(-) in various natural freshwater samples.
      Stable scintillating particles were formed by preparing the vinyl monomer 2-[4
      (4'-vinylbiphenylyl)]-5-(4-tert-butylphenyl)-1,3,4-oxadiazole (vPBD), starting
      with the commercial organic flour TBut-PBD and its subsequent copolymerization
      with styrene, divinylbenzene, and p-chloromethylstyrene mixture. To integrate the
      radiochemical separation and radiometric detection steps within the same bead,
      the chloromethyl groups of the scintillating resins were subjected to amination
      reactions with dioctylamine (DOA) and trioctylamine (TOA). On-line quantification
      of (99)TcO4(-) was achieved by packing the scintillating anion-exchange resin
      into Teflon tubing for quantification by a flow scintillation analyzer (FSA). The
      two functionalized resins were selective for pertechnetate over the common anions
      in natural freshwaters, especially Cl(-) and SO4(2-) with up to 1000 ppm and with
      up to 10 ppm I(-) and Cr2O7(2-). The uptake efficiency of the TOA sensor
      decreased from 97.88% to 85.08% in well water and river water, respectively,
      while the counting efficiency was almost constant (69.50%). The DOA performance
      showed lower efficiency in the two water types relative to TOA. On the other
      hand, the DOA sensor could be regenerated by 5 M HNO3 for reuse at least four
      times without losing its chemical or optical performance. The detection limit was
      1.45 Bq which could be achieved by loading 45 mL from well and tap water
      containing the maximum contaminant level (MCL) of (99)Tc (33 Bq/L).

PMID- 24012765
TI  - Soil gas radon concentrations measurements in terms of great soil groups.
AB  - In this study, soil gas radon concentrations were investigated according to
      locations, horizontal soil layers and great soil groups around Tuzla Fault,
      Seferihisar-Izmir. Great soil groups are a category that described the horizontal
      soil layers under soil classification system and distributions of radon
      concentration in the great soil groups are firstly determined by the present
      study. According to the obtained results, it has been showed that the radon
      concentrations in the Koluvial soil group are higher than the other soil groups
      in the region. Also significant differences on location in same great soil group
      were determined. The radon concentrations in the Koluvial soil groups were
      measured with respect to soil layers structures (A, B, C1, and C2). It has been
      observed that the values increase with depth of soil (C2>C1>B>A). The main reason
      may be due to the meteorological factors that have limited effect on radon escape
      from deep layers. Although fault lines pass thought the study area radon
      concentrations were varied location to location, layer to layer and great group
      to great group. The study shows that a detailed location description should be
      performed before soil radon measurements for earthquake predictions. 

PMID- 24012766
TI  - Minocycline and doxycycline, but not other tetracycline-derived compounds,
      protect liver cells from chemical hypoxia and ischemia/reperfusion injury by
      inhibition of the mitochondrial calcium uniporter.
AB  - Minocycline, a tetracycline-derived compound, mitigates damage caused by
      ischemia/reperfusion (I/R) injury. Here, 19 tetracycline-derived compounds were
      screened in comparison to minocycline for their ability to protect hepatocytes
      against damage from chemical hypoxia and I/R injury. Cultured rat hepatocytes
      were incubated with 50MUM of each tetracycline-derived compound 20 min prior to
      exposure to 500MUM iodoacetic acid plus 1mM KCN (chemical hypoxia). In other
      experiments, hepatocytes were incubated in anoxic Krebs-Ringer-HEPES buffer at
      pH6.2 for 4h prior to reoxygenation at pH7.4 (simulated I/R). Tetracycline
      derived compounds were added 20 min prior to reperfusion. Ca(2+) uptake was
      measured in isolated rat liver mitochondria incubated with Fluo-5N. Cell killing
      after 120 min of chemical hypoxia measured by propidium iodide (PI) fluorometry
      was 87%, which decreased to 28% and 42% with minocycline and doxycycline,
      respectively. After I/R, cell killing at 120 min decreased from 79% with vehicle
      to 43% and 49% with minocycline and doxycycline. No other tested compound
      decreased killing. Minocycline and doxycycline also inhibited mitochondrial
      Ca(2+) uptake and suppressed the Ca(2+)-induced mitochondrial permeability
      transition (MPT), the penultimate cause of cell death in reperfusion injury.
      Ru360, a specific inhibitor of the mitochondrial calcium uniporter (MCU), also
      decreased cell killing after hypoxia and I/R and blocked mitochondrial Ca(2+)
      uptake and the MPT. Other proposed mechanisms, including mitochondrial
      depolarization and matrix metalloprotease inhibition, could not account for
      cytoprotection. Taken together, these results indicate that minocycline and
      doxycycline are cytoprotective by way of inhibition of MCU.

PMID- 24012767
TI  - Acute hyperglycemia worsens ischemic stroke-induced brain damage via high
      mobility group box-1 in rats.
AB  - Hyperglycemia adversely affects the outcome of ischemic stroke. Extracellular
      HMGB1 plays a role in aggravating brain damage in the postischemic brain. The aim
      of this study was to determine whether the extracellular HMGB1 is involved in the
      worsened ischemic damage during hyperglycemic stroke. Male Wistar rats underwent
      middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Acute
      hyperglycemia was induced by an injection of 50% dextrose. Rats received
      glycyrrhizin, a specific HMGB1 inhibitor, or vehicle. HMGB-1 in cerebrospinal
      fluid and in brain parenchyma was detected at 2 or 4 h post-reperfusion.
      Neurological deficits, infarct volume and cerebral edema were assessed 24 h post
      MCAO the disruption of blood-brain barrier (BBB) and the expression of tight
      junction protein Occludin were measured at 4 h post-reperfusion. Hyperglycemia
      enhanced the early release of HMGB1 from ischemic brain tissue, which was
      accompanied by increased infarct volume, neurological deficit, cerebral edema and
      BBB disruption. Glycyrrhizin alleviated the aggravation of infarct volume,
      neurological deficit, cerebral edema and BBB disruption by decreasing the
      degradation of tight junction protein Occludin in the ischemic hemisphere of
      hyperglycemic rats. In conclusion, enhanced early extracellular release of HMGB1
      might represent an important mechanism for worsened ischemic damage, particularly
      early BBB disruption, during hyperglycemic stroke. An HMGB1 inhibitor
      glycyrrhizin is a potential therapeutic option for hyperglycemic stroke.

PMID- 24012768
TI  - Vestibular insights into cognition and psychiatry.
AB  - The vestibular system has traditionally been thought of as a balance apparatus;
      however, accumulating research suggests an association between vestibular
      function and psychiatric and cognitive symptoms, even when balance is measurably
      unaffected. There are several brain regions that are implicated in both
      vestibular pathways and psychiatric disorders. The present review examines the
      anatomical associations between the vestibular system and various psychiatric
      disorders. Despite the lack of direct evidence for vestibular pathology in the
      key psychiatric disorders selected for this review, there is a substantial body
      of literature implicating the vestibular system in each of the selected
      psychiatric disorders. The second part of this review provides complimentary
      evidence showing the link between vestibular dysfunction and vestibular
      stimulation upon cognitive and psychiatric symptoms. In summary, emerging
      research suggests the vestibular system can be considered a potential window for
      exploring brain function beyond that of maintenance of balance, and into areas of
      cognitive, affective and psychiatric symptomology. Given the paucity of
      biological and diagnostic markers in psychiatry, novel avenues to explore brain
      function in psychiatric disorders are of particular interest and warrant further
      exploration.

PMID- 24012770
TI  - Changes in the protein patterns in pea (Pisum sativum L.) roots under the
      influence of long- and short-term chilling stress and post-stress recovery.
AB  - Amongst many factors restricting geographical distribution of plants and crop
      productivity, low temperature is one of the most important. To gain better
      understanding of the molecular response of germinating pea (Pisum sativum L.) to
      low temperature, we investigated the influence of long and short chilling stress
      as well as post-stress recovery on the alterations in the root proteomes. The
      impact of long stress was examined on the pea seeds germinating in the continuous
      chilling conditions of 10  degrees C for 8 days (LS). To examine the impact of
      short stress, pea seeds germinating for 72 h in the optimal temperature of 20 
      degrees C were subjected to 24-h chilling (SS). Additionally, both stress
      treatments were followed by 24 h of recovery in the optimal conditions
      (accordingly LSR and SR). Using the 2D gel electrophoresis and MALDI-TOF MS
      protein identification, it was revealed, that most of the proteins undergoing
      regulation under the applied conditions were implicated in metabolism, protection
      against stress, cell cycle regulation, cell structure maintenance and hormone
      synthesis, which altogether may influence root growth and development in the
      early stages of plant life. The obtained results have shown that most of detected
      alterations in the proteome patterns of pea roots are dependent on stress
      duration. However, there are some analogical response pathways which are
      triggered regardless of stress length. The functions of proteins which
      accumulation has been changed by chilling stress and post-stress recovery are
      discussed here in relation to their impact on pea roots development.

PMID- 24012769
TI  - Synchronization dynamics induced on pairs of neurons under applied weak
      alternating magnetic fields.
AB  - Pairs of Helix aspersa neurons show an alternating magnetic field dependent
      frequency synchronization (AMFS) when exposed to a weak (amplitude B0 between 0.2
      and 150 Gauss (G)) alternating magnetic field (AMF) of extremely low frequency
      (ELF, fM = 50 Hz). We have compared the AMFS patterns of discharge with: i) the
      synaptic activity promoted by glutamate and acetylcholine; ii) the activity
      induced by caffeine; iii) the bioelectric activity induced on neurons
      interconnected by electric synapses. AMFS activity reveals several specific
      features: i) a tight coincidence in time of the pattern and frequency, f, of
      discharge; ii) it is induced in the time interval of field application; iii) it
      is dependent on the intensity of the sinusoidal applied magnetic field; iv)
      elicited biphasic responses (excitation followed by inhibition) run in parallel
      for the pair of neurons; and v) some neuron pairs either spontaneously or AMF
      synchronized can be desynchronized under applied higher AMF. Our electron
      microscopy studies reveal gap-like junctions confirming our immunocytochemistry
      results about expression of connexin 26 (Cx26) in 4.7% of Helix neurons. AMF and
      carbenoxolone did not induce any significant effect on spontaneous
      synchronization through electric synapses.

PMID- 24012771
TI  - Kinetics of the transformation of n-propyl gallate and structural analogs in the
      perfused rat liver.
AB  - n-Propyl gallate and its analogs are used in foods and other products to prevent
      oxidation. In the liver the compound exerts several harmful effects, especially
      gluconeogenesis inhibition. The mode of transport and distribution of n-propyl
      gallate and its kinetics of biotransformation have not yet been investigated. To
      fill this gap the transformation, transport and distribution of n-propyl gallate
      and two analogs were investigated in the rat liver. Isolated perfused rat liver
      was used. n-Propyl gallate, methyl gallate, n-octyl gallate and transformation
      products were quantified by high pressure-liquid chromatography coupled to
      fluorescence detection. The interactions of n-propyl gallate and analogs with the
      liver presented three main characteristics: (1) the hydrolytic release of gallic
      acid from n-propyl gallate and methyl gallate was very fast compared with the
      subsequent transformations of the gallic acid moiety; (2) transport of the esters
      was very fast and flow-limited in contrast to the slow and barrier-limited
      transport of gallic acid; (3) the apparent distribution volume of n-propyl
      gallate, but probably also of methyl gallate and n-octyl gallate, greatly
      exceeded the water space in the liver, contrary to the gallic acid space which is
      smaller than the water space. It can be concluded that at low portal
      concentrations (<50MUM) the gallic acid esters are 100% extracted during a single
      passage through the liver, releasing mainly gallic acid into the systemic
      circulation. For the latter a considerable time is required until complete
      biotransformation. The exposure of the liver to the esters, however, is quite
      prolonged due to extensive intracellular binding. 

PMID- 24012772
TI  - Changes of early post-traumatic osteoarthritis in an ovine model of simulated ACL
      reconstruction are associated with transient acute post-injury synovial
      inflammation and tissue catabolism.
AB  - The study described here tested the hypothesis that early intra-articular
      inflammation is associated with the development of post-traumatic osteoarthritis
      (PTOA) in a sheep model. We extended previously published work in which we
      investigated joint gross morphology and synovial mRNA expression of inflammatory
      and catabolic molecules 2 weeks after anatomic Anterior cruciate ligament (ACL)
      autograft reconstructive surgery (ACL-R). The same variables have been analyzed
      at 20 weeks post surgery together with new experimental variables at both time
      points. Animals were sacrificed at 20 weeks post ACL-R surgery and their joints
      graded for signs of PTOA. Synovial samples were harvested for histological
      grading plus mRNA and protein analysis for a panel of inflammatory and catabolic
      molecules. The mRNA expression levels for this panel plus connective tissue
      matrix turnover molecules were also investigated in cartilage samples. Results of
      gross morphological assessments at 20 weeks post surgery showed some changes
      consistent with early OA, but indicated little progression of damage from the 2
      week time point. While significant alterations in mRNA levels for synovial
      inflammatory and catabolic molecules were detected at 2 weeks, values had
      normalized by 20 weeks. Similarly, all mRNA expression levels for inflammatory
      and catabolic molecules in articular cartilage had returned to normal levels by
      20 weeks post ACL-R surgery. We conclude that synovial inflammatory processes are
      initiated very early after ACL-R surgery and may instigate events that lead to
      the gross cartilage and joint abnormalities observed as early as 2 weeks.
      However, the absence of sustained inflammation and joint instability may prevent
      OA progression. 

PMID- 24012773
TI  - Self-aligned colocalization of 3D plasmonic nanogap arrays for ultra-sensitive
      surface plasmon resonance detection.
AB  - We report extremely sensitive plasmonic detection that was performed label-free
      based on the colocalization of target DNA molecules and electromagnetic hot spots
      excited at 3D nanogap arrays. The colocalization was self-aligned by oblique
      evaporation of a dielectric mask over the 3D nanopatterns, which creates nanogaps
      for spatially selective target binding. The feasibility was experimentally
      confirmed by measuring hybridization of 24-mer single-stranded DNA
      oligonucleotides on triangular and circular 3D nanogap arrays. We were able to
      achieve significantly amplified optical signatures that lead to sensitivity
      enhancement in terms of detectable binding capacity in reference to conventional
      thin film-based surface plasmon resonance detection on the order of 1 fg/mm(2).

PMID- 24012774
TI  - Into the groove: can rhythm influence Parkinson's disease?
AB  - Previous research has noted that music can improve gait in several pathological
      conditions, including Parkinson's disease, Huntington's disease and stroke.
      Current research into auditory-motor interactions and the neural bases of musical
      rhythm perception has provided important insights for developing potential
      movement therapies. Specifically, neuroimaging studies show that rhythm
      perception activates structures within key motor networks, such as premotor and
      supplementary motor areas, basal ganglia and the cerebellum - many of which are
      compromised to varying degrees in Parkinson's disease. It thus seems likely that
      automatic engagement of motor areas during rhythm perception may be the
      connecting link between music and motor improvements in Parkinson's disease. This
      review seeks to describe the link, address core questions about its underlying
      mechanisms, and examine whether it can be utilized as a compensatory mechanism. 

PMID- 24012775
TI  - Apolipoprotein A-II is a key regulatory factor of HDL metabolism as appears from
      studies with transgenic animals and clinical outcomes.
AB  - The structure and metabolism of HDL are linked to their major apolipoproteins
      (apo) A-I and A-II. HDL metabolism is very dynamic and depends on the constant
      remodeling by lipases, lipid transfer proteins and receptors. HDL exert several
      cardioprotective effects, through their antioxidant and antiinflammatory
      capacities and through the stimulation of reverse cholesterol transport from
      extrahepatic tissues to the liver for excretion into bile. HDL also serve as
      plasma reservoir for C and E apolipoproteins, as transport vehicles for a great
      variety of proteins, and may have more physiological functions than previously
      recognized. In this review we will develop several aspects of HDL metabolism with
      emphasis on the structure/function of apo A-I and apo A-II. An important
      contribution to our understanding of the respective roles of apo A-I and apo A-II
      comes from studies using transgenic animal models that highlighted the
      stabilizatory role of apo A-II on HDL through inhibition of their remodeling by
      lipases. Clinical studies coupled with proteomic analyses revealed the presence
      of dysfunctional HDL in patients with cardiovascular disease. Beyond HDL
      cholesterol, a new notion is the functionality of HDL particles. In spite of
      abundant literature on HDL metabolic properties, a major question remains
      unanswered: which HDL particle(s) confer(s) protection against cardiovascular
      risk? 

PMID- 24012776
TI  - A prawn transglutaminase: molecular characterization and biochemical properties.
AB  - In this study, we report the bioinformatics characterization, gene expression,
      transglutaminase activity and coagulation assays of transglutaminase (TGase) of
      freshwater prawn Macrobrachium rosenbergii identified from the constructed cDNA
      library by GS FLXTM technology. Even though, TGase have sequence similarity, they
      differ extensively in their substrate specificity and are thought to play an
      important in variety of functions such as development, tissue differentiation and
      immune responses etc. Gene expression studies show that MrTGase is widely
      distributed in the tissues such as heart, muscle, intestine, brain, etc., but
      higher amounts are found in hemocyte. Results of TGase mRNA relative expression
      in hemocyte, before and after infected with white spot syndrome baculovirus
      (WSBV) and Vibrio harveyi show that the gene expression initially increases up to
      24 h and then it falls down. Coagulation assay results showed that the endogenous
      TGase is involved in the rapid assembly of a specific, plasma clotting protein.
      Structural studies show that MrTGase contains a typical TGc domain between 323
      and 424, and two putative integrin-binding motifs at Arg(180)-Gly(181)-Asp(182)
      and Arg(269)-Gly(270)-Asp(271). The predicted 3D model of MrTGase contains 47.04%
      coils (366 amino acid residues), 26.74% extended strand (208 residues), 21.72%
      alpha-helix (169 residues) and 4.5% beta turns (35 residues). BLASTp analysis of
      MrTGase exhibited high sequence similarities with other crustacean TGase, with
      the highest observed in white shrimp (77.1%). Moreover, the phylogenetic analysis
      also showed that MrTGase clustered with the other members of crustacean TGase.
      Overall, these results suggested that MrTGase is a major and functional TGase of
      M. rosenbergii for haemolymph coagulation and also in spread of infection.

PMID- 24012777
TI  - n-3 polyunsaturated fatty acids and HER2-positive breast cancer: interest of the
      fat-1 transgenic mouse model over conventional dietary supplementation.
AB  - Overexpression of the tyrosine kinase receptor ErbB2/HER2/Neu, occurs in 25%-30%
      of invasive breast cancer (BC) with poor patient prognosis. Even if numerous
      studies have shown prevention of breast cancer by n-3 fatty acid intake, the
      experimental conditions under which n-3 fatty acids exert their protective effect
      have been variable from study to study, preventing unifying conclusions. Due to
      confounding factors, inconsistencies still remain regarding protective effects of
      n-3 polyunsaturated fatty acids (PUFA) on BC. When animals are fed with dietary
      supplementation in n-3 fatty acids (the traditional approach to modify tissue
      content and decrease the n-6/n-3 ratio) complex dietary interactions can occur
      among dietary lipids (antioxidants, vitamins...) that can modulate the activity
      of n-3 fatty acids. So, what are the specific roles of these n-3 PUFA in reducing
      breast cancer risk and particularly preventing HER2-positive breast cancer? In
      this review, we discuss crucial points that may account for discrepancies of
      results and provide a highly effective genetic approach that can eliminate
      confounding factors of diet for evaluating the molecular mechanisms of n-3 PUFA
      in HER2 signaling pathway regulation. The fat-1 transgenic mouse model is capable
      of converting n-6 to n-3 fatty acids leading to an increase in n-3 fatty acid
      content with a balanced n-6/n-3 fatty acid ratio in all tissues. The fat-1 mouse
      model allows well-controlled studies in HER2-positive breast cancer prevention to
      be performed, without the conflict of potential confounding factors of diet.

PMID- 24012778
TI  - Epidermal growth factor stimulates proliferation and migration of porcine
      trophectoderm cells through protooncogenic protein kinase 1 and extracellular
      signal-regulated kinases 1/2 mitogen-activated protein kinase signal transduction
      cascades during early pregnancy.
AB  - For successful implantation and establishment of early epitheliochorial
      placentation, porcine conceptuses require histotroph, including nutrients and
      growth factors, secreted by or transported into the lumen of the uterus.
      Epidermal growth factor (EGF), an essential component of histotroph, is known to
      have potential growth-promoting activities on the conceptus and uterine
      endometrium. However, little is known about its effects to transactivate cell
      signaling cascades responsible for proliferation, growth and differentiation of
      conceptus trophectoderm. In the present study, therefore, we determined that EGFR
      mRNA and protein were abundant in endometrial luminal and glandular epithelia,
      stratum compactum stroma and conceptus trophectoderm on days 13-14 of pregnancy,
      but not in any other cells of the uterus or conceptus. In addition, primary
      porcine trophectoderm (pTr) cells treated with EGF exhibited increased abundance
      of phosphorylated (p)-AKT1, p-ERK1/2 MAPK and p-P90RSK over basal levels within
      5min, and effect that was maintained to between 30 and 120min. Immunofluorescence
      microscopy revealed abundant amounts of p-ERK1/2 MAPK and p-AKT1 proteins in the
      nucleus and, to a lesser extent, in the cytoplasm of pTr cells treated with EGF
      as compared to control cells. Furthermore, the abundance of p-AKT1 and p-ERK1/2
      MAPK proteins was inhibited in control and EGF-treated pTr cells transfected with
      EGFR siRNA. Compared to the control siRNA transfected pTr cells, pTr cells
      transfected with EGFR siRNA exhibited an increase in expression of IFND and
      TGFB1, but there was no effect of expression of IFNG. Further, EGF stimulated
      proliferation and migration of pTr cells through activation of the PI3K-AKT1 and
      ERK1/2 MAPK-P90RSK cell signaling pathways. Collectively, these results support
      the hypothesis that EGF coordinately activates multiple cell signaling pathways
      critical to proliferation, migration and survival of trophectoderm cells that are
      critical to development of porcine conceptuses during implantation and
      placentation. 

PMID- 24012780
TI  - Mineralocorticoid receptor antagonists attenuate pulmonary inflammation and
      bleomycin-evoked fibrosis in rodent models.
AB  - Accumulating evidence indicates protective actions of mineralocorticoid
      antagonists (MR antagonists) on cardiovascular pathology, which includes blunting
      vascular inflammation and myocardial fibrosis. We examined the anti-inflammatory
      and anti-fibrotic potential of MR antagonists in rodent respiratory models. In an
      ovalbumin allergic and challenged Brown Norway rat model, the total cell count in
      nasal lavage was 29,348 +/- 5451, which was blocked by spironolactone (0.3-60
      mg/kg, p.o.) and eplerenone (0.3-30 mg/kg, p.o.). We also found that MR
      antagonists attenuated pulmonary inflammation in the Brown Norway rat. A series
      of experiments were conducted to determine the actions of MR blockade in
      acute/chronic lung injury models. (1) Ex vivo lung slice rat experiments found
      that eplerenone (0.01 and 10 uM) and spironolactone (10 uM) diminished lung
      hydroxyproline concentrations by 55 +/- 5, 122 +/- 9, and 83 +/- 8%. (2) In in
      vivo studies, MR antagonists attenuated the increases in bronchioalveolar lavage
      (BAL) neutrophils and macrophages caused by lung bleomycin exposure. In separate
      studies, bleomycin (4.0 U/kg, i.t.) increased lung levels of hydroxyproline by
      approximately 155%, which was blocked by spironolactone (10-60 mg/kg, p.o.). In a
      rat Lipopolysaccharide (LPS) model, spironolactone inhibited acute increases in
      BAL cytokines with moderate effects on neutrophils. Finally, we found that
      chronic LPS exposure significantly increased end expiratory lung and decreased
      lung elastance in the mouse. These functional effects of chronic LPS were
      improved by MR antagonists. Our results demonstrate that MR antagonists have
      significant pharmacological actions in the respiratory system.

PMID- 24012779
TI  - Carney complex and McCune Albright syndrome: an overview of clinical
      manifestations and human molecular genetics.
AB  - Endocrine neoplasia syndromes feature a wide spectrum of benign and malignant
      tumors of endocrine and non-endocrine organs associated with other clinical
      manifestations. This study outlines the main clinical features, genetic basis,
      and molecular mechanisms behind two multiple endocrine neoplasia syndromes that
      share quite a bit of similarities, but one can be inherited whereas the other is
      always sporadic, Carney complex (CNC) and McCune-Albright (MAS), respectively.
      Spotty skin pigmentation, cardiac and other myxomas, and different types of
      endocrine tumors and other characterize Carney complex, which is caused largely
      by inactivating Protein kinase A, regulatory subunit, type I, Alpha (PRKAR1A)
      gene mutations. The main features of McCune-Albright are fibrous dysplasia of
      bone (FD), cafe-au-lait macules and precocious puberty; the disease is caused by
      activating mutations in the Guanine Nucleotide-binding protein, Alpha-stimulating
      activity polypeptide (GNAS) gene which are always somatic. We review the clinical
      manifestations of the two syndromes and provide an update on their molecular
      genetics. 

PMID- 24012781
TI  - Antagonising EP1 and EP2 receptors reveal that the TP receptor mediates a
      component of antigen-induced contraction of the guinea pig trachea.
AB  - The role of different cyclooxygenase (COX) metabolites released after antigen
      exposure has been difficult to assess due to simultaneous release of dominant
      constrictors such as histamine and cysteinyl-leukotrienes (CysLT). In addition
      prostaglandin E2 (PGE2) also has a powerful effect on basal tone. The aim was to
      exclude PGE2, histamine and CysLTs from the antigen-induced contraction to define
      the possible involvement of remaining COX metabolites. Isometric force was
      measured in guinea pig trachea after exposure to cumulatively increasing
      concentrations of ovalbumin (OVA; 0.1 ng/ml to 0.1 mg/ml) in the absence or
      presence of biosynthesis inhibitors and receptor antagonists. Challenge with OVA
      induced a concentration-dependent contraction that reached 75% of maximal tissue
      response. COX-inhibition or a combination of EP1 and EP2 receptor antagonism (ONO
      8130 and PF-04418948) completely abolished the tone, resulting in an augmented
      antigen response. COX inhibition in combination with either antihistamines or
      antileukotrienes (FLAP inhibitor or CysLT1-2 receptor antagonist) displayed no
      difference compared to COX inhibition alone. However, a combination of all three
      classes reduced the contraction to 30%, revealing an unknown contractile
      component. Exchanging COX inhibition with EP1-2 receptor antagonists together
      with antihistamines and antileukotrienes could not decrease the contraction more
      than to 50%. However, when a TP receptor antagonist (SQ-29,548) was further
      included, the maximal antigen contraction reached 30%, similar as previously,
      clearly revealing a TP-mediated contractile component. PGE2 primarily regulate
      the basal tone via EP1 and EP2, whereas prostanoids, such as TXA2 and PGD2,
      contribute as mediator of the antigen-response by activation of the TP receptor.

PMID- 24012782
TI  - Acamprosate {monocalcium bis(3-acetamidopropane-1-sulfonate)} reduces ethanol
      drinking behavior in rats and glutamate-induced toxicity in ethanol-exposed
      primary rat cortical neuronal cultures.
AB  - Acamprosate, the calcium salt of bis(3-acetamidopropane-1-sulfonate), contributes
      to the maintenance of abstinence in alcohol-dependent patients, but its mechanism
      of action in the central nervous system is unclear. Here, we report the effect of
      acamprosate on ethanol-drinking behavior in standard laboratory Wistar rats,
      including voluntary ethanol consumption and the ethanol-deprivation effect. After
      forced ethanol consumption arranged by the provision of only one drinking bottle
      containing 10% ethanol, the rats were given a choice between two drinking
      bottles, one containing water and the other containing 10% ethanol. In rats
      selected for high ethanol preference, repeated oral administration of acamprosate
      diminished voluntary ethanol drinking. After three months of continuous access to
      two bottles, rats were deprived of ethanol for three days and then presented with
      two bottles again. After ethanol deprivation, ethanol preference was increased,
      and the increase was largely abolished by acamprosate. After exposure of primary
      neuronal cultures of rat cerebral cortex to ethanol for four days, neurotoxicity,
      as measured by the extracellular leakage of lactate dehydrogenase (LDH), was
      induced by incubation with glutamate for 1h followed by incubation in the absence
      of ethanol for 24h. The N-methyl-D-aspartate receptor blocker 5-methyl-10,11
      dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine, the metabotropic glutamate
      receptor subtype 5 antagonist 6-methyl-2-(phenylethynyl)pyridine and the voltage
      gated calcium-channel blocker nifedipine all inhibited glutamate-induced LDH
      leakage from ethanol-exposed neurons. Acamprosate inhibited the glutamate-induced
      LDH leakage from ethanol-exposed neurons more strongly than that from intact
      neurons. In conclusion, acamprosate showed effective reduction of drinking
      behavior in rats and protected ethanol-exposed neurons by multiple blocking of
      glutamate signaling.

PMID- 24012783
TI  - Timing in a variable interval procedure: evidence for a memory singularity.
AB  - Rats were trained in either a 30 s peak-interval procedure, or a 15-45 s variable
      interval peak procedure with a uniform distribution (Exp 1) or a ramping
      probability distribution (Exp 2). Rats in all groups showed peak shaped response
      functions centered around 30 s, with the uniform group having an earlier and
      broader peak response function and rats in the ramping group having a later peak
      function as compared to the single duration group. The changes in these mean
      functions, as well as the statistics from single trial analyses, can be better
      captured by a model of timing in which memory is represented by a single,
      average, delay to reinforcement compared to one in which all durations are stored
      as a distribution, such as the complete memory model of Scalar Expectancy Theory
      or a simple associative model. This article is part of a Special Issue entitled:
      Associative and Temporal Learning.

PMID- 24012784
TI  - Atypical and classical forms of the disease-associated state of the prion protein
      exhibit distinct neuronal tropism, deposition patterns, and lesion profiles.
AB  - A number of disease-associated PrP forms characterized by abnormally short
      proteinase K-resistant fragments (atypical PrPres) were recently described in
      prion diseases. The relationship between atypical PrPres and PrP(Sc), and their
      role in etiology of prion diseases, remains unknown. We examined the relationship
      between PrP(Sc) and atypical PrPres, a form characterized by short C-terminal
      proteinase K-resistant fragments, in a prion strain of synthetic origin. We found
      that the two forms exhibit distinct neuronal tropism, deposition patterns, and
      degree of pathological lesions. Immunostaining of brain regions demonstrated a
      partial overlap in anatomic involvement of the two forms and revealed the sites
      of their selective deposition. The experiments on amplification in vitro
      suggested that distinct neuronal tropism is attributed to differences in
      replication requirements, such as preferences for different cellular cofactors
      and PrP(C) glycoforms. Remarkably, deposition of atypical PrPres alone was not
      associated with notable pathological lesions, suggesting that it was not
      neurotoxic, but yet transmissible. Unlike PrP(Sc), atypical PrPres did not show
      significant perineuronal, vascular, or perivascular immunoreactivity. However,
      both forms showed substantial synaptic immunoreactivity. Considering that
      atypical PrPres is not associated with substantial lesions, this result suggests
      that not all synaptic disease-related PrP states are neurotoxic. The current work
      provides important new insight into our understanding of the structure
      pathogenicity relationships of transmissible PrP states.

PMID- 24012785
TI  - Is Erica tetralix abundance on wet heathlands controlled by nitrogen deposition
      or soil acidification?
AB  - Erica tetralix is the key species on NW European wet heathlands, where it is
      often found to be the dominating plant species. Consequently, it is of
      considerable concern that the species has decreased significantly in cover from
      28% to 18% over a six-year period. In order to understand the underlying causes,
      a structural equation modeling (SEM) approach was applied on ecological data from
      1130 wet heathland plots. Both atmospheric N deposition and soil acidification
      were included in the SEM. The most important causal effect revealed by the SEM
      was a significant negative effect of N deposition on the cover of E. tetralix,
      whereas soil acidity tended to have a negative effect of relatively less
      importance. There was no significant effect of N deposition on soil pH, which
      indicates that there are no major indirect effects of N deposition on the cover
      of E. tetralix mediated by soil acidification. 

PMID- 24012786
TI  - Applications in environmental risk assessment of leucocyte apoptosis, necrosis
      and respiratory burst analysis on the European bullhead, Cottus sp.
AB  - The use of a biochemical multi-biomarker approach proved insufficient to obtain
      clear information about ecosystem health. The fish immune system is considered as
      an attractive non-specific marker for environmental biomonitoring which has
      direct implications in individual fitness and population growth. Thus, the
      present work proposes the use of fish immunomarkers together with more common
      biochemical biomarkers in sampling conditions optimized to reduce biomarker
      variability and increase parameter robustness. European bullheads (Cottus sp.)
      from 11 stations in the Artois-Picardie watershed (France) were sampled. In the
      multiple discriminant analysis, the sites were highly correlated with apoptosis,
      respiratory burst, GST and EROD activities. Moreover, the use together of
      biochemical and immune markers increased the percentage of fish correctly classed
      at each site and enhanced site separation. This study argues in favor of the
      utilization of apoptosis, necrosis and respiratory burst for the determination of
      environmental risk assessment in addition to the set of biochemical biomarkers
      commonly used in fish. 

PMID- 24012788
TI  - Identification of novel micropollutants in wastewater by a combination of suspect
      and nontarget screening.
AB  - To detect site-specific, suspected and formerly unknown contaminants in a
      wastewater treatment plant effluent, we established a screening procedure based
      on liquid chromatography-high resolution mass spectrometry (LC-HRMS) with
      stepwise identification schemes. Based on automated substructure searches a list
      of 2160 suspected site-specific and documented water contaminants was reduced to
      those amenable to LC-HRMS. After searching chromatograms for exact masses of
      suspects, presumably false positive detections were stepwise excluded by
      retention time prediction, the evaluation of isotope patterns, ionization
      behavior, and HRMS/MS spectra. In nontarget analysis, peaks for identification
      were selected based on distinctive isotope patterns and intensity. The stepwise
      identification of nontarget compounds was automated by a plausibility check of
      molecular formulas using the Seven Golden Rules, an exclusion of compounds with
      presumably low commercial importance and an automated HRMS/MS evaluation. Six
      suspected and five nontarget chemicals were identified, of which two have not
      been previously reported as environmental pollutants. 

PMID- 24012787
TI  - Field measurement on the emissions of PM, OC, EC and PAHs from indoor crop straw
      burning in rural China.
AB  - Field measurements were conducted to measure emission factors of particulate
      matter (EFPM), organic carbon (EFOC), elemental carbon (EFEC), 28 parent
      polycyclic aromatic hydrocarbons (EF28pPAHs), and 4 oxygenated PAHs (EF4oPAHs)
      for four types of crop straws burned in two stoves with similar structure but
      different ages. The average EFPM, EFOC, EFEC, EF28pPAHs, and EF4oPAHs were 9.1 +/
      5.7 (1.8-22 as range), 2.6 +/- 2.9 (0.30-12), 1.1 +/- 1.2 (0.086-5.5), 0.26 +/-
      0.19 (0.076-0.96), 0.011 +/- 0.14 (1.3 * 10(-4) - 0.063) g/kg, respectively. Much
      high EF28pPAHs was observed in field compared with the laboratory derived EFs and
      significant difference in EF28pPAHs was identified among different crop residues,
      indicating considerable underestimation when laboratory derived EFs were used in
      the inventory. The field measured EFPM, EFOC, and EFEC were significantly
      affected by stove age and the EFs of carbonaceous particles for the 15-year old
      stove were approximately 2.5 times of those for the 1-year old stove. 

PMID- 24012789
TI  - Identifying post-translational modifications of NEMO by tandem mass spectrometry
      after high affinity purification.
AB  - An integral component of NF-kappaB signalling is NEMO, NF-kappaB essential
      modulator, a regulatory protein of the IkappaB kinase (IKK) complex. Post
      translational modifications of NEMO, including phosphorylation, SUMOylation, and
      ubiquitination are critical events during stimuli induced NF-kappaB activation.
      Here we demonstrate a method to detect post-translational modifications of NEMO
      using cells stably expressing polyhistidine tagged NEMO which allows for high
      affinity purification of NEMO following rapid denaturing lysis and
      characterization by MS/MS. We identified a previously uncharacterized basal
      phosphorylation of NEMO at Serine 387 and tested the biological significance of
      this phosphorylation through a somatic genetic complementation analysis using the
      NEMO mutants S387A, S388D, and P388I in 1.3E2 NEMO-deficient murine pre-B cells.
      NF-kappaB signalling induced by bacterial lipopolysaccharide, Interleukin-1beta
      or the DNA damaging agent etoposide was not perturbed by these mutations of NEMO.
      Thus, S387 phosphorylation of NEMO is not a general requirement to mediate
      efficient NF-kappaB signalling and therefore may have cell type and/or stimulus
      specific activity in vivo. 

PMID- 24012790
TI  - Production and secretion of Lactobacillus crispatus beta-galactosidase in Pichia
      pastoris.
AB  - Lactobacillus beta-galactosidases are mostly heterodimeric proteins, which are
      encoded by the two overlapping genes, lacL and lacM, and produced in recombinant
      prokaryotic systems for higher yield. This is the first report on the expression
      of a heterodimeric beta-galactosidase from Lactobacillus crispatus B470 in Pichia
      pastoris. The overlapping consecutive genes, lacL and lacM, that shared 17
      nucleotides were cloned from the genomic DNA of L. crispatus. A recombinant
      plasmid harboring both expression cassettes of lacL and lacM was constructed and
      transformed into P. pastoris GS115 competent cells. Two recombinant P. pastoris
      strains (GSLac01 and GSLac02) showed the highest beta-galactosidase activities of
      24.5 and 31.0 U/ml in the culture supernatants, respectively. The recombinant
      beta-galactosidase (LcLacLM) from GSLac02 was purified to electrphoretic
      homogeneity by ion-exchange chromatography and molecular sieve chromatography.
      Similar to most Lactobacillus beta-galactosidases that operate at moderately
      thermophilic and weak acid to neutral conditions, LcLacLM showed optimal activity
      at 50 degrees C and pH 5.5-6.5. It's the first report on functional and secretory
      expression of LacLM-type beta-galactosidase in eukaryotic system. This strategy
      might be applied to the expression of other overlapping genes.

PMID- 24012791
TI  - Development of the Twin-Strep-tag(r) and its application for purification of
      recombinant proteins from cell culture supernatants.
AB  - Short peptide affinity tags have become indispensable in protein research. They
      cannot only be used for affinity purification but also downstream for detection
      and assay of an arbitrary fused recombinant protein without the need for any
      prior knowledge of its biochemical properties. Strep-tag(r)II is particularly
      popular for providing recombinant proteins at high purity and functionality by
      using physiological conditions within a rapid one-step protocol. The affinity
      receptor for Strep-tag(r)II is affinity engineered streptavidin, named Strep
      Tactin(r). Strep-tag(r)II binds to the biotin binding pocket enabling mild
      competitive elution with biotin derivatives, preferably desthiobiotin, for
      repeated use of the Strep-Tactin(r) affinity resins. Fast binding and
      dissociation kinetics allow comparatively high flow rates throughout column
      chromatography including elution. Fast dissociation kinetics may be, however,
      limiting for using Strep-tag(r)II for direct purification of target proteins from
      large volumes of diluted extracts like mammalian cell culture supernatants or in
      assay formats requiring extended washing like ELISA. For this reason, binding
      characteristics were improved by development of the Twin-Strep-tag(r) consisting
      of two Strep-tag(r)II moieties connected by a short linker. The resulting avidity
      effect, i.e., the combined synergistic binding of two Strep-tag(r)II moieties to
      tetrameric Strep-Tactin(r), reduces the off-rate for more steady binding under
      non-competitive conditions. The addition of a competitor, however, reverses the
      synergistic avidity effect and, hence, efficient elution capability is preserved.
      In fact, the Twin-Strep-tag(r) features all beneficial properties of Strep
      tag(r)II, including efficient elution under gentle competitive conditions, but,
      due to its higher affinity, additionally enables a more universal use in
      applications requiring stable binding. 

PMID- 24012792
TI  - E6 protein of human papillomavirus 16 (HPV16) expressed in Escherichia coli sans
      a stretch of hydrophobic amino acids, enables purification of GST-DeltaE6 in the
      soluble form and retains the binding ability to p53.
AB  - Recombinant E6 expressed in Escherichia coli is known to form recalcitrant
      inclusion bodies even when fused to the soluble GST protein. This study describes
      the modification of the HPV genotype-16 oncogenic protein E6 in order to obtain
      it in the soluble form. The modified protein (DeltaE6) was expressed in E. coli
      BL21 as an N-terminal fusion with GST (GST-DeltaE6). DeltaE6 was constructed by
      deleting the nucleotide sequences coding for IHDIIL (31-36 a.a), one of the
      highly hydrophobic peptide stretches, using splicing by overextension polymerase
      chain reaction (SOE-PCR). The removal of IHDIIL residues rendered the GST-DeltaE6
      soluble and amenable for purification involving a two step process a preliminary
      glutathione-GST affinity chromatography followed by gel-filtration
      chromatography. Evaluation of purified protein fractions by HPLC suggests that
      GST-DeltaE6 exists as a monomer. Further, the DeltaE6 in GST-DeltaE6 seemed to
      retain the binding ability to p53 as determined by the glutathione-GST capture
      ELISA. Purified GST-DeltaE6 we reckon, might find use as an essential reagent in
      immunological assays, in sero-epidemiological studies, and also in studies to
      delineate the structure and function of HPV16 E6. 

PMID- 24012793
TI  - Optimization of separation and digestion conditions in immune complexome
      analysis.
AB  - Immune complexome analysis is a method for identifying and profiling of antigens
      in circulating immune complexes (CICs); it involves separation of immune
      complexes from serum, direct tryptic digestion of these complexes, and protein
      analysis via nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS).
      To improve this method, we initially investigated the effects of two factors-the
      gradient elution program and nano-LC column type (C18-packed, C8-packed, or
      packed spray capillary column)-on the numbers of peptides and proteins
      identified. Longer gradient elution times resulted in higher identification
      capability throughout the range of 25-400 min. Moreover, the packed spray
      capillary column supported identification of more peptides and proteins than did
      any other column. In addition, microwave-assisted digestion was compared with
      conventional digestion, which involved incubation overnight at 37  degrees C.
      Microwave-assisted digestion produced more partially digested peptides than did
      conventional digestion. However, the percentages of miscleaved peptides in all of
      the identified peptides in microwave-assisted digestion of immune complexes (a
      protein mixture) were lower than those in the physical stimulation-assisted
      digestion of a model protein. Microwave-assisted digestion is slightly inferior
      to, or as effective as, conventional digestion, but it drastically reduces the
      digestion time.

PMID- 24012794
TI  - Firefly luciferase as the reporter for transcriptional response to the
      environment in Escherichia coli.
AB  - We demonstrate that firefly luciferase is a good reporter in Escherichia coli for
      transcription dynamics in response to the environment. E. coli strains, carrying
      a fusion of the promoter of the ycgZ gene and the coding region of the luciferase
      gene, showed transient bioluminescence on receiving blue light. This response was
      compromised in mutants lacking known regulators in manners consistent with each
      regulator's function. We also show that relA, a gene encoding a (p)ppGpp
      synthetase, affects ycgZ dynamics when nullified. Moreover, two unstable
      luciferase variants showed improved response dynamics and should be useful to
      study quick changes of gene expression. 

PMID- 24012795
TI  - The dopamine antagonist cis-flupenthixol blocks the expression of the conditioned
      positive but not the negative effects of cocaine in rats.
AB  - Human cocaine users report that the initial "high" produced by cocaine
      administration is followed by an anxiogenic "crash". Given that cocaine has such
      robust and opposing properties, it is likely that both positive and negative
      effects of cocaine contribute to an individual's motivation to administer the
      drug. Despite this likelihood, the neurobiology underlying cocaine's dual
      processes remains unclear. While much literature supports a role for dopamine
      (DA) in cocaine reward, it is uncertain if DA also contributes to the drug's
      negative effects. Our laboratory has extensively utilized a modified conditioned
      place test to explore cocaine's opponent processes. In this paradigm rats develop
      conditioned place preferences (CPPs) for an environment paired with the
      immediate/positive effects of cocaine, and conditioned place aversions (CPAs) for
      an environment paired with the delayed/negative effects present 15-min after i.v.
      injection. In the current study rats were conditioned to associate an environment
      with either the immediate or delayed effects of i.v. cocaine (1mg/kg/0.1ml) 3h
      after i.p. pre-treatment with either the DA D1/D2 receptor antagonist cis
      flupenthixol (0.5mg/kg/ml) or saline vehicle. As expected, vehicle-treated
      control animals developed the normal pattern of CPPs for cocaine's immediate
      effects or CPAs for the delayed effects of cocaine. However, while DA receptor
      antagonism prevented the expression of cocaine CPPs it did not alter the
      expression of cocaine-induced CPAs. These data confirm a role for DA transmission
      in cocaine reward but suggest that different neural pathways mediate the drug's
      negative/anxiogenic properties. 

PMID- 24012797
TI  - Toll-like receptors as therapeutic targets for cancer.
AB  - Stimulation of Toll-like receptors (TLRs) to activate the innate immune system
      has been a legitimate therapeutic strategy for some years. TLRs 3, 4, 7, 8 and 9
      are all validated targets for cancer and a number of companies are developing
      agonists and vaccine adjuvants. TLR7 in particular has established proof-of
      concept as a target in the topical treatment of bladder and skin cancers.
      However, the development of systemic treatments targeting TLR7 for most other
      cancers has proved difficult owing to cardiotoxicity or myelosuppression.
      Tantalisingly, recent animal data have demonstrated that a new class of modified
      TLR7 agonists can be administered systemically with a good toxicology profile,
      opening up this target in therapeutic interventions for systemic cancers. 

PMID- 24012796
TI  - Transdermal delivery of cannabidiol attenuates binge alcohol-induced
      neurodegeneration in a rodent model of an alcohol use disorder.
AB  - Excessive alcohol consumption, characteristic of alcohol use disorders, results
      in neurodegeneration and behavioral and cognitive impairments that are
      hypothesized to contribute to the chronic and relapsing nature of alcoholism.
      Therefore, the current study aimed to advance the preclinical development of
      transdermal delivery of cannabidiol (CBD) for the treatment of alcohol-induced
      neurodegeneration. In Experiment 1, 1.0%, 2.5% and 5.0% CBD gels were evaluated
      for neuroprotection. The 5.0% CBD gel resulted in a 48.8% reduction in
      neurodegeneration in the entorhinal cortex assessed by Fluoro-Jade B (FJB), which
      trended to statistical significance (p=0.069). Treatment with the 5.0% CBD gel
      resulted in day 3 CBD plasma concentrations of ~100.0 ng/mL so this level was
      used as a target concentration for development of an optimized gel formulation.
      Experiment 2 tested a next generation 2.5% CBD gel formulation, which was
      compared to CBD administration by intraperitoneal injection (IP; 40.0 mg/kg/day).
      This experiment found similar magnitudes of neuroprotection following both routes
      of administration; transdermal CBD decreased FJB+ cells in the entorhinal cortex
      by 56.1% (p<0.05), while IP CBD resulted in a 50.6% (p<0.05) reduction in FJB+
      cells. These results demonstrate the feasibility of using CBD transdermal
      delivery systems for the treatment of alcohol-induced neurodegeneration.

PMID- 24012798
TI  - Carvedilol efficiently protects kidneys without affecting the antitumor efficacy
      of cisplatin in mice.
AB  - Cisplatin is an effective anticancer drug which has been used to treat a wide
      range of tumors for the last 30 years. However, its use is associated with
      nephrotoxicity. Protective strategies have been reported, but their impact on the
      antitumor activity of cisplatin has not been clarified. We have previously
      reported the protective potential of carvedilol against cisplatin nephrotoxicity
      in tumor-free rats. Therefore, in the present study we used a tumor-bearing model
      to investigate the impact of carvedilol on the antitumor activity of cisplatin.
      The renal damage induced by cisplatin and the protective effect of carvedilol
      were demonstrated by the levels of blood urea nitrogen and plasma creatinine as
      well as by renal histopathology and immunohistochemistry. The mechanism of
      protection was associated with significantly decreased (i) oxidative stress
      markers, (ii) Bax expression, (iii) caspase-3 activity and (iv) TUNEL labeling
      for apoptosis. More importantly, evaluation of tumor mass, tumor remission rate
      and the survival curve showed that carvedilol did not impair the antitumor action
      of cisplatin. These findings suggest that the mechanisms underlying the
      nephrotoxic and the antitumor activity of cisplatin might be different. This is
      the first study to report such findings. Compared to other reported potential
      cytoprotectors against cisplatin-induced nephrotoxicity, carvedilol stands out
      due to the fact that it is already clinically-employed and well tolerated by the
      patients. Based on these features and on the present findings, carvedilol is a
      very promising candidate for future clinical trials as nephroprotector in
      patients treated with cisplatin.

PMID- 24012799
TI  - Virological characteristics of cervical cancers carrying pure episomal form of
      HPV16 genome.
AB  - OBJECTIVE: Many studies on integration have reported conflicting results
      regarding the role of HPV integration in cervical cancer. We hypothesized that
      high viral load and disruption of E2 gene associated with integration of HPV were
      not the only pathway leading to cancer development. METHODS: This study analysed
      the viral load and integration status of HPV16, measured the HPV16 E6/E7 mRNA
      transcript levels, delineated the E2 and LCR sequence variation, and determined
      the methylation status of two E2 binding sites. RESULTS: The results showed that
      viral load was not associated with the physical status of HPV genome. Levels of
      the three E6/E7 mRNA transcripts in invasive cervical cancers containing purely
      episomal viral genome were found to be similar to those containing integrated
      viral genome, suggesting that cancers containing episomal viral genome were also
      mediated by an up-regulated E6/E7 mRNA expression, and more importantly, did not
      depend on integration and disruption of the E2 gene. CONCLUSIONS: The alternative
      mechanism that up-regulated the expression of E6 and E7 in invasive cancers
      harbouring episomal viral genome was likely to be a consequence of methylation of
      the two E2 binding sites located at the promoter region of HPV16. These
      observations are in line with the hypothesis that HPV integration was not the
      only mechanism leading to the development of cervical cancer.

PMID- 24012800
TI  - HER2/neu gene amplification determines the sensitivity of uterine serous
      carcinoma cell lines to AZD8055, a novel dual mTORC1/2 inhibitor.
AB  - OBJECTIVE: To evaluate c-erbB2 gene amplification in a series of primary uterine
      serous carcinoma (USC) cell lines. To assess the efficacy of AZD8055, a novel
      dual mTORC1/2 inhibitor against primary HER2/neu amplified vs HER2/neu not
      amplified USC cell lines. METHODS: Twenty-two primary USC cell lines were
      evaluated for c-erbB2 oncogene amplification by FISH assays. In vitro sensitivity
      to AZD8055 was evaluated by flow-cytometry-based viability and proliferation
      assays. Cell cycle profile and downstream cellular responses to AZD8055 were
      assessed by measuring the DNA content of cells and by phosphorylation of the S6
      protein by flow-cytometry. RESULTS: Nine of 22 (40.9%) USC cell lines
      demonstrated c-erbB2 gene amplification by FISH. AZD8055 caused a strong
      differential growth inhibition in USC cell lines, with high HER-2/neu-expressors
      demonstrating significantly higher sensitivity when compared to low HER-2/neu
      expressors (AZD-8055 IC50 mean+/-SEM=0.27+/-0.05MUM in c-erbB2 amplified versus
      1.67+/-0.68MUM in c-erbB2 not amplified tumors, P=0.03). AZD8055 growth
      inhibition was associated with a significant and dose-dependent increase in the
      percentage of cells blocked in the G0/G1 cell cycle phase and a dose-dependent
      decline in pS6 levels in both c-erbB2 amplified vs c-erbB2 not amplified USC cell
      lines. CONCLUSIONS: AZD8055 may represent a novel targeted therapeutic agent in
      patients harboring advanced/recurrent/refractory USC. c-erbB2 gene amplification
      may represent a biomarker to identify USC patients who may benefit most from the
      use of AZD8055.

PMID- 24012801
TI  - The downside of strong emotional memories: how human memory-related genes
      influence the risk for posttraumatic stress disorder--a selective review.
AB  - A good memory for emotionally arousing experiences may be intrinsically adaptive,
      as it helps the organisms to predict safety and danger and to choose appropriate
      responses to prevent potential harm. However, under conditions of repeated
      exposure to traumatic stressors, strong emotional memories of these experiences
      can lead to the development of trauma-related disorders such as posttraumatic
      stress disorder (PTSD). This syndrome is characterized by distressing intrusive
      memories that can be so intense that the survivor is unable to discriminate past
      from present experiences. This selective review on the role of memory-related
      genes in PTSD etiology is divided in three sections. First, we summarize studies
      indicating that the likelihood to develop PTSD depends on the cumulative exposure
      to traumatic stressors and on individual predisposing risk factors, including a
      substantial genetic contribution to PTSD risk. Second, we focus on memory
      processes supposed to be involved in PTSD etiology and present evidence for PTSD
      associated alterations in both implicit (fear conditioning, fear extinction) and
      explicit memory for emotional material. This is supplemented by a brief
      description of structural and functional alterations in memory-relevant brain
      regions in PTSD. Finally, we summarize a selection of studies indicating that
      genetic variations found to be associated with enhanced fear conditioning,
      reduced fear extinction or better episodic memory in human experimental studies
      can have clinical implications in the case of trauma exposure and influence the
      risk of PTSD development. Here, we focus on genes involved in noradrenergic
      (ADRA2B), serotonergic (SLC6A4), and dopaminergic signaling (COMT) as well as in
      the molecular cascades of memory formation (PRKCA and WWC1). This is supplemented
      by initial evidence that such memory-related genes might also influence the
      response rates of exposure-based psychotherapy or pharmacological treatment of
      PTSD, which underscores the relevance of basic memory research for disorders of
      altered memory functioning such as PTSD. 

PMID- 24012802
TI  - Systemic inhibition of mTOR kinase via rapamycin disrupts consolidation and
      reconsolidation of auditory fear memory.
AB  - The mammalian target of rapamycin (mTOR) kinase is a critical regulator of mRNA
      translation and is known to be involved in various long lasting forms of synaptic
      and behavioural plasticity. However, information concerning the temporal pattern
      of mTOR activation and susceptibility to pharmacological intervention during both
      consolidation and reconsolidation of long-term memory (LTM) remains scant. Male
      C57BL/6 mice were injected systemically with rapamycin at various time points
      following conditioning or retrieval in an auditory fear conditioning paradigm,
      and compared to vehicle (and/or anisomycin) controls for subsequent memory
      recall. Systemic blockade of mTOR with rapamycin immediately or 12h after
      training or reactivation impairs both consolidation and reconsolidation of an
      auditory fear memory. Further behavioural analysis revealed that the enduring
      effects of rapamycin on reconsolidation are dependent upon reactivation of the
      memory trace. Rapamycin, however, has no effect on short-term memory or the
      ability to retrieve an established fear memory. Collectively, our data suggest
      that biphasic mTOR signalling is essential for both consolidation and
      reconsolidation-like activities that contribute to the formation, re
      stabilization, and persistence of long term auditory-fear memories, while not
      influencing other aspects of the memory trace. These findings also provide
      evidence for a cogent treatment model for reducing the emotional strength of
      established, traumatic memories analogous to those observed in acquired anxiety
      disorders such as posttraumatic stress disorder (PTSD) and specific phobias,
      through pharmacologic blockade of mTOR using systemic rapamycin following
      reactivation. 

PMID- 24012803
TI  - Advances in the neurobiology of hearing disorders: recent developments regarding
      the basis of tinnitus and hyperacusis.
AB  - The prevalence of hearing problems in the Western world has, due to aging of the
      population, doubled over the past 30 years. Thereby, noise-induced hearing loss
      is an important factor that worsens over time in addition to age-related hearing
      loss. Hearing loss is usually measured as an elevation of a person's hearing
      thresholds, expressed in decibel (dB). However, recent animal studies have
      unraveled a type of permanent cochlear damage, without an elevation of hearing
      thresholds. This subtle damage is linked to a permanent and progressive
      degeneration of auditory fibers that occurs in association with damage of the
      inner hair cell synapse. Afferent neuronal degeneration has been suggested to be
      involved in hyperacusis (over sensitivity to sound) and tinnitus (a phantom sound
      percept). Hyperacusis and tinnitus are potentially devastating conditions that
      are still incurable. The main risk factors to develop tinnitus or hyperacusis are
      hearing loss, social stress and age. Both tinnitus and hyperacusis have been
      discussed in the context of a pathological increased response gain in subcortical
      brain regions as a reaction to deprivation of sensory input. Novel studies
      confirm the involvement of peripheral deafferentation for tinnitus and
      hyperacusis, but suggest that the disorder results from different brain responses
      to different degrees of deafferentation: while tinnitus may arise as a failure of
      the brain to adapt to deprived peripheral input, hyperacusis may result from an
      'over-adaptive' increase in response gain. Moreover, moderate and high stress
      levels at the time of acoustic trauma have been suggested to play a pivotal role
      in the vulnerability of the cochlea to acoustic damage and therefore for the
      development of tinnitus and hyperacusis. 

PMID- 24012804
TI  - Preparation and characterization of three dimensional graphene foam supported
      platinum-ruthenium bimetallic nanocatalysts for hydrogen peroxide based
      electrochemical biosensors.
AB  - The large surface, the excellent dispersion and the high degrees of sensitivity
      of bimetallic nanocatalysts were the attractive features of this investigation.
      Graphene foam (GF) was a three dimensional (3D) porous architecture consisting of
      extremely large surface and high conductive pathways. In this study, 3D GF was
      used incorporating platinum-ruthenium (PtRu) bimetallic nanoparticles as an
      electrochemical nanocatalyst for the detection of hydrogen peroxide (H2O2).
      PtRu/3D GF nanocatalyst exhibited a remarkable performance toward electrochemical
      oxidation of H2O2 without any additional mediator showing a high sensitivity
      (1023.1 uA mM(-1)cm(-2)) and a low detection limit (0.04 uM) for H2O2.
      Amperometric results demonstrated that GF provided a promising platform for the
      development of electrochemical sensors in biosensing and PtRu/3D GF nanocatalyst
      possessed the excellent catalytic activity toward the H2O2 detection. A small
      particle size and a high degree of the dispersion in obtaining of large active
      surface area were important for the nanocatalyst for the best H2O2 detection in
      biosensing. Moreover, potential interference by ascorbic acid and uric acid
      appeared to be negligible.

PMID- 24012805
TI  - Ligation Chain Reaction based gold nanoparticle assembly for ultrasensitive DNA
      detection.
AB  - A simple and ultrasensitive DNA biosensor was developed utilizing the color and
      size changes originating from Ligation Chain Reaction (LCR)-based gold
      nanoparticle assembly as an indicator. Using synthetic DNA of 10-fold serial
      dilutions as a target, the limit of detection (LOD) was 1.5 aM with a range of
      DNA concentrations from 0.01 to 1000 fM by UV-vis absorption and 0.1 aM in the
      range of 0.01-10,000 fM by dynamic light scattering (DLS). This developed method
      is low-cost, rapid, and much lower LOD for the detection of specific short DNA
      sequences, and the results can be directly determined either by the color or by
      the DLS. The capability of high-throughput detection with the aid of PCR
      amplification apparatus can also be realized.

PMID- 24012806
TI  - Comparison of gene expression profiles in primary and immortalized human
      pterygium fibroblast cells.
AB  - PURPOSE: Pterygium is a fibrovascular growth on the ocular surface with corneal
      tissue destruction, matrix degradation and varying extents of chronic
      inflammation. To facilitate investigation of pterygium etiology, we immortalized
      pterygium fibroblast cells and profiled their global transcript levels compared
      to primary cultured cells. METHODS: Fibroblast cells were cultured from
      surgically excised pterygium tissue using the explant method and propagated to
      passage number 2-4. We hypothesized that intervention with 3 critical molecular
      intermediates may be necessary to propage these cells. Primary fibroblast cells
      were immortalized sequentially by a retroviral construct containing the human
      telomerase reverse transcriptase gene and another retroviral expression vector
      expressing p53/p16 shRNAs. Primary and immortalized fibroblast cells were
      evaluated for differences in global gene transcript levels using an Agilent
      Genechip microarray. RESULTS: Light microscopic morphology of immortalized cells
      was similar to primary pterygium fibroblast at passage 2-4. Telomerase reverse
      transcriptase was expressed, and p53 and p16 levels were reduced in immortalized
      pterygium fibroblast cells. There were 3308 significantly dysregulated genes
      showing at least 2 fold changes in transcript levels between immortalized and
      primary cultured cells (2005 genes were up-regulated and 1303 genes were down
      regulated). Overall, 13.58% (95% CI: 13.08-14.10) of transcripts in immortalized
      cells were differentially expressed by at least 2 folds compared to primary
      cells. CONCLUSION: Pterygium primary fibroblast cells were successfully
      immortalized to at least passage 11. Although a variety of genes are
      differentially expressed between immortalized and primary cells, only genes
      related to cell cycle are significantly changed, suggesting that the immortalized
      cells may be used as an in vitro model for pterygium pathology.

PMID- 24012807
TI  - Mechanism of cysteine oxidation by peroxynitrite: An integrated experimental and
      theoretical study.
AB  - Since peroxynitrite was identified as a pathophysiological agent it has been
      implicated in a great variety of cellular processes. Particularly, peroxynitrite
      mediated oxidation of cellular thiol-containing compounds such as Cys residues,
      is a key event which has been extensively studied. Although great advances have
      been accomplished, the reaction is not completely understood at the atomic level.
      Aiming to shed light on this subject, we present an integrated kinetic and
      theoretical study of the oxidation of free Cys by peroxynitrite. We determined pH
      independent thermodynamic activation parameters, namely those corresponding to
      the reaction between the reactive species: Cys thiolate and peroxynitrous acid.
      We found a pH-independent activation energy of 8.2 +/- 0.6 kcal/mol. Simulations
      were performed using state of the art hybrid quantum-classical (QM-MM) molecular
      dynamics simulations. Our results are consistent with a SN2 mechanism, with Cys
      sulfenic acid and nitrite anion as products. The activation barrier is mostly due
      to the alignment of sulfur's thiolate atom with the oxygen atoms of the peroxide,
      along with the concomitant charge reorganization and important changes in the
      solvation profile. This work provides an atomic detailed description of the
      reaction mechanism and a framework to understand the environment effects on
      peroxynitrite reactivity with protein thiols.

PMID- 24012808
TI  - Molecular dynamics study of the structural basis of dysfunction and the
      modulation of reactive oxygen species generation by pathogenic mutants of human
      dihydrolipoamide dehydrogenase.
AB  - Human dihydrolipoamide dehydrogenase (LADH, E3) is a component in the pyruvate-,
      alpha-ketoglutarate- and branched-chain ketoacid dehydrogenase complexes and in
      the glycine cleavage system. The pathogenic mutations of LADH cause severe
      metabolic disturbances, called E3 deficiency that often involve cardiological and
      neurological symptoms and premature death. Our laboratory has recently shown that
      some of the known pathogenic mutations augment the reactive oxygen species (ROS)
      generation capacity of LADH, which may contribute to the clinical presentations.
      A recent report concluded that elevated oxidative stress generated by the above
      mutants turns the lipoic acid cofactor on the E2 subunits dysfunctional. In the
      present contribution we generated by molecular dynamics (MD) simulation the
      conformation of LADH that is proposed to be compatible with ROS generation. We
      propose here for the first time the structural changes, which are likely to turn
      the physiological LADH conformation to its ROS-generating conformation. We also
      created nine of the pathogenic mutants of the ROS-generating conformation and
      again used MD simulation to detect structural changes that the mutations induced
      in this LADH conformation. We propose the structural changes that may lead to the
      modulation in ROS generation of LADH by the pathogenic mutations. 

PMID- 24012809
TI  - UDP-galactopyranose mutases from Leishmania species that cause visceral and
      cutaneous leishmaniasis.
AB  - Leishmaniasis is a vector-borne, neglected tropical disease caused by parasites
      from the genus Leishmania. Galactofuranose (Galf) is found on the cell surface of
      Leishmania parasites and is important for virulence. The flavoenzyme that
      catalyzes the isomerization of UDP-galactopyranose to UDP-Galf, UDP
      galactopyranose mutase (UGM), is a validated drug target in protozoan parasites.
      UGMs from L. mexicana and L. infantum were recombinantly expressed, purified, and
      characterized. The isolated enzymes contained tightly bound flavin cofactor and
      were active only in the reduced form. NADPH is the preferred redox partner for
      both enzymes. A kcat value of 6 +/- 0.4s(-1) and a Km value of 252 +/- 42 MUM
      were determined for L. infantum UGM. For L. mexicana UGM, these values were ~4
      times lower. Binding of UDP-Galp is enhanced 10-20 fold in the reduced form of
      the enzymes. Changes in the spectra of the reduced flavin upon interaction with
      the substrate are consistent with formation of a flavin-iminium ion intermediate.

PMID- 24012810
TI  - Increased myocardial short-range forces in a rodent model of diabetes reflect
      elevated content of beta myosin heavy chain.
AB  - Diastolic dysfunction is a clinically significant problem for patients with
      diabetes and often reflects increased ventricular stiffness. Attached cross
      bridges contribute to myocardial stiffness and produce short-range forces, but it
      is not yet known whether these forces are altered in diabetes. In this study, we
      tested the hypothesis that cross-bridge-based short-range forces are increased in
      the streptozotocin (STZ) induced rat model of type 1 diabetes. Chemically
      permeabilized myocardial preparations were obtained from 12week old rats that had
      been injected with STZ or vehicle 4weeks earlier, and activated in solutions with
      pCa (=-log10[Ca(2+)]) values ranging from 9.0 to 4.5. The short-range forces
      elicited by controlled length changes were ~67% greater in the samples from the
      diabetic rats than in the control preparations. This change was mostly due to an
      increased elastic limit (the length change at the peak short-range force) as
      opposed to increased passive muscle stiffness. The STZ-induced increase in short
      ranges forces is thus unlikely to reflect changes to titin and/or collagen
      filaments. Gel electrophoresis showed that STZ increased the relative expression
      of beta myosin heavy chain. This molecular mechanism can explain the increased
      short-ranges forces observed in the diabetic tissue if beta myosin molecules
      remain bound between the filaments for longer durations than alpha molecules
      during imposed movements. These results suggest that interventions that decrease
      myosin attachment times may be useful treatments for diastolic dysfunction
      associated with diabetes. 

PMID- 24012812
TI  - A direct primary afferent projection of the trigeminal nerve to the valvula
      cerebelli in the spiny eel Macrognathus zebrinus.
AB  - This study is a re-examination of the direct primary sensory input to the valvula
      cerebelli in spiny eel. The valvula in Macrognathus zebrinus receives a primary
      afferent projection from the trigeminal nerve as revealed by injections of
      biotinylated dextran amines into the rostrum. The descending trigeminal nucleus
      and nucleus of the tractus solitarius are innervated as well. Injections with DiI
      into the valvula labeled fibers in the descending trigeminal nucleus. The
      projection of tactile information from the rostrum to the valvula may be an
      adaptation of food search for spiny eels in regard to their highly mobile
      rostrum. 

PMID- 24012811
TI  - Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured
      rats.
AB  - Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of
      spinal surgery. In an attempt to establish a preventive therapy for anticipated
      SC injury, we tested the effect of a single dose (SD) vaccine vs. the addition of
      a booster dose (BD) of a neural-derived peptide (A91) prior to SC contusion.
      Immunization with A91 immediately after SC injury has demonstrated to induce
      significant tissue protection and motor recovery. After injury, only the BD
      vaccination schedule had a neuroprotective effect. It was capable of improving
      neurological recovery that was always significantly higher than the one observed
      in rats with SD immunization or those only treated with PBS. Toward the end of
      study, animals treated with an A91 BD presented a BBB score of 9.75+/-0.17
      (mean+/-standard deviation) while rats treated with SD or PBS had a score of
      6.6+/-0.7 and 5.6+/-0.6 respectively. In the next step we attempted to
      corroborate the neuroprotective effect induced by A91 immunization. For this
      purpose, we assessed the survival of rubrospinal neurons (RSNs) and ventral horn
      neurons (VHNs) sixty days after SC injury. BD vaccination induced a significant
      survival of both RSNs and VHNs after injury. Finally, the failure or success of
      this therapy (SD or BD respectively) was associated with a lower (SD) or higher
      (BD) A91-specific T cell proliferation. Prophylactic neuroprotection with an
      initial and subsequent booster dose of A91 may improve recovery after SC injury
      sustained during invasive spinal surgery procedures. 

PMID- 24012813
TI  - Refining the time course of facilitation and inhibition in attention and action.
AB  - According to action-centred models of attention, there is a tight coupling
      between attention and response planning processes. In support of these models,
      previous research has shown that reach trajectories deviate towards a cue at
      short (<100ms) cue-target onset asynchronies (CTOAs) and away from a cue
      presented at longer CTOAs (>750ms). These deviations resemble the pattern of
      facilitatory and inhibitory reaction time (RT) effects observed in keypress
      studies. Here, participants reached to targets following a non-predictive cue and
      5 CTOAs (from 100 to 600ms in 125ms intervals) were used to gain a deeper
      understanding of the relationship between RT and trajectory effects. Consistent
      with action-centred attention, facilitatory and inhibitory cuing after-effects
      were present in RTs and trajectories. Interestingly, RT and trajectory effects
      were temporally staggered: facilitatory effects were present in trajectories at
      the 100ms CTOA when they had already dissipated in RTs, and inhibitory effects
      were present in RTs (>=350ms CTOAs) before they were detected in trajectories
      (600ms CTOA). The time courses of the cuing effects suggest that, although action
      and attention systems are tightly coupled, the facilitatory and inhibitory
      mechanisms operate in attention before affecting action planning. 

PMID- 24012814
TI  - Immunohistochemical demonstration of urocortin 1 in Edinger-Westphal nucleus of
      the human neonate: colocalization with tyrosine hydroxylase under acute perinatal
      hypoxia.
AB  - Perinatal hypoxia could cause long-term disturbances of the dopaminergic (DA)
      systems, leading to behavioral and/or neurological deficits later in life.
      Increased expression of tyrosine hydroxylase (TH) was shown in the substantia
      nigra (SN) and ventral tegmental area (VTA) of human neonates that suffered
      severe/acute perinatal hypoxic insults, but also in all neurons of the Edinger
      Westphal nucleus (EW). Since EW, in humans, contains urocortin 1 (UCN1)/centrally
      projecting neurons (EWcp), we investigated: (a) the development of UCN1-positive
      neurons and the possible effect of neonatal hypoxic/ischemic encephalopathy on
      UCN1 expression and (b) the possible colocalization of UCN1 with TH in neonates
      with histological signs of acute hypoxic injury. Our results showed that in EWcp
      of the human neonate, UCN1-immunoreactivity was already evident from 34 weeks of
      gestation onwards at very low levels. No UCN1-immunoreactivity was found in
      neurons of SN or VTA. In EWcp, a positive correlation was found between UCN1
      expression and the age of the neonates, but not with hypoxia neuropathological
      grade. UCN1 was colocalized with TH in most EWcp neurons. Since UCN1 in EWcp may
      play a significant role in stress adaptation and consequently in stress-related
      disorders, the role of catecholamine synthesis in this nucleus under acute
      hypoxic conditions must be further investigated. 

PMID- 24012815
TI  - Phasic nicotinic potentiation of frog retinotectal transmission facilitates
      eliciting of higher activity level of the tectum column.
AB  - Nicotinic acetylcholine receptors contribute to the mediation of cholinergic role
      in attention, vigilance, orienting and detection of behavioral significant
      stimuli. We have recently demonstrated an increase of the intrinsic recurrent
      excitatory activity of the tectum column caused by the phasic (after-burst)
      nicotinic potentiation of a frog single axon retinotectal transmission to the
      tectum layer F. We have shown in the present study that the phasic nicotinic
      potentiation facilitates eliciting of higher activity level of the tectum column
      featured by generation of output signals from the tectum column. Since these
      signals can lead to an escape from danger reactions, a functional significance of
      nicotinic modulation of the neural network has been demonstrated. The phasic
      nicotinic potentiation that facilitates eliciting of higher activity level of the
      tectum column can be considered as a mechanism of vigilance and cue detection at
      the level of small neural network. 

PMID- 24012816
TI  - The relationship between five widely-evaluated variants in CDKN2A/B and CDKAL1
      genes and the risk of type 2 diabetes: a meta-analysis.
AB  - The genes encoding two cyclin-dependent kinases-inhibitor-2A/B (CDKN2A/B) and 5
      regulatory subunit-associated protein-like 1 (CDKAL1) have been investigated
      extensively in associations with type 2 diabetes; the results, however, are often
      irreproducible. We therefore sought to evaluate these associations by performing
      a meta-analysis on five widely-evaluated variants from the two genes. There were
      38 studies (patients/controls: 51,940/52,234) for rs10811661, 16 studies
      (20,029/24,419) for rs564398 in CDKN2A/B gene, and 27 studies (28,383/47,635) for
      rs7756992, 26 studies (28,816/31,713) for rs7754840, 21 studies (29,260/38,400)
      for rs10946398 in CDKAL1 gene. Overall risk estimates for type 2 diabetes
      conferred by rs10811661-T, rs564398-A, rs7754840-C, rs7756992-G, and rs10946398-C
      alleles were 1.17 (95% CI: 1.10-1.23; P<0.0005; I(2)=83.9%), 1.1 (95% CI: 1.0
      1.21; P=0.051; I(2)=88.3%), 1.24 (95% CI: 1.18-1.3; P<0.0005; I(2)=74.3%), 1.2
      (95% CI: 1.11-1.3; P<0.0005; I(2)=92.0%), and 1.19 (95% CI: 1.1-1.29; P<0.0005;
      I(2)=90.8%), respectively. There was evident publication bias for rs564398 and
      rs7754840. Subgroup analyses by ethnicity showed remarkable divergences in risk
      estimate for rs564398 between Asians (odds ratio [OR]=1.01; 95% CI: 0.86-1.19;
      P=0.868) and Caucasians (OR=1.19; 95% CI: 1.03-1.35; P=0.012) (P<0.05). For all
      variants examined, the results of studies in retrospective design or with
      population-based controls were comparative with that of overall studies. In meta
      regression analyses, age was found to exert a significant influence on the
      association between rs10811661 and type 2 diabetes (P=0.003), as well as between
      rs7754840 and gender (P=0.034). Taken together, our findings provide evidence for
      a significant contribution of CDKN2A/B gene rs10811661 and CDKAL1 gene rs7756992
      and rs10946398 to type 2 diabetes.

PMID- 24012817
TI  - Assessment of gene set analysis methods based on microarray data.
AB  - Gene set analysis (GSA) incorporates biological information into statistical
      knowledge to identify gene sets differently expressed between two or more
      phenotypes. It allows us to gain an insight into the functional working mechanism
      of cells beyond the detection of differently expressed gene sets. In order to
      evaluate the competence of GSA approaches, three self-contained GSA approaches
      with different statistical methods were chosen; Category, Globaltest and
      Hotelling's T(2) together with their assayed power to identify the differences
      expressed via simulation and real microarray data. The Category does not take
      care of the correlation structure, while the other two deal with correlations. In
      order to perform these methods, R and Bioconductor were used. Furthermore, venous
      thromboembolism and acute lymphoblastic leukemia microarray data were applied.
      The results of three GSAs showed that the competence of these methods depends on
      the distribution of gene expression in a dataset. It is very important to assay
      the distribution of gene expression data before choosing the GSA method to
      identify gene sets differently expressed between phenotypes. On the other hand,
      assessment of common genes among significant gene sets indicated that there was a
      significant agreement between the result of GSA and the findings of biologists. 

PMID- 24012818
TI  - ChAy/Bx, a novel chimeric high-molecular-weight glutenin subunit gene apparently
      created by homoeologous recombination in Triticum turgidum ssp. dicoccoides.
AB  - High-molecular-weight glutenin subunits (HMW-GSs) are of considerable interest,
      because they play a crucial role in determining dough viscoelastic properties and
      end-use quality of wheat flour. In this paper, ChAy/Bx, a novel chimeric HMW-GS
      gene from Triticum turgidum ssp. dicoccoides (AABB, 2n=4x=28) accession D129, was
      isolated and characterized. Sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis revealed that the electrophoretic mobility of
      the glutenin subunit encoded by ChAy/Bx was slightly faster than that of 1Dy12.
      The complete ORF of ChAy/Bx contained 1,671 bp encoding a deduced polypeptide of
      555 amino acid residues (or 534 amino acid residues for the mature protein),
      making it the smallest HMW-GS gene known from Triticum species. Sequence analysis
      showed that ChAy/Bx was neither a conventional x-type nor a conventional y-type
      subunit gene, but a novel chimeric gene. Its first 1305 nt sequence was highly
      homologous with the corresponding sequence of 1Ay type genes, while its final 366
      nt sequence was highly homologous with the corresponding sequence of 1Bx type
      genes. The mature ChAy/Bx protein consisted of the N-terminus of 1Ay type subunit
      (the first 414 amino acid residues) and the C-terminus of 1Bx type subunit (the
      final 120 amino acid residues). Secondary structure prediction showed that
      ChAy/Bx contained some domains of 1Ay subunit and some domains of 1Bx subunit.
      The special structure of this HMW glutenin chimera ChAy/Bx subunit might have
      unique effects on the end-use quality of wheat flour. Here we propose that
      homoeologous recombination might be a novel pathway for allelic variation or
      molecular evolution of HMW-GSs.

PMID- 24012819
TI  - Therapy of chronic hepatitis C virus infection in the era of direct-acting and
      host-targeting antiviral agents.
AB  - OBJECTIVES: Chronic hepatitis C virus (HCV) infection represents a leading
      worldwide medical and social problem. The expanding knowledge of HCV lifecycle
      has led to the development of novel antiviral agents that: a) specifically target
      a viral function (direct-acting antivirals), or b) specifically inhibit viral
      replication. The present review describes the novel anti-HCV drugs that have been
      better studied at the time of this writing and the current two types of
      treatment, namely interferon-based and interferon-free regimens. In addition,
      predictive factors, virological responses, side-effects, and resistance
      mechanisms of the novel agents are summarized. CONCLUSIONS: The introduction of
      novel antiviral agents is remarkably changing the therapeutic combinations aimed
      at improving virological responses both for easy-to-cure and difficult-to-treat
      patients. Since additional, effective drugs are under advanced development, it
      seems reasonable to expect that further therapeutic and prognostic improvements
      will be achieved in the near future.

PMID- 24012820
TI  - Increased teicoplanin doses are associated with improved serum levels but not
      drug toxicity.
AB  - OBJECTIVE: Teicoplanin is widely used for the treatment of severe gram-positive
      infection, aiming to achieve trough serum levels of 20-60 mg/L for patients with
      severe infection. A standard 400 mg daily dose is frequently associated with sub
      therapeutic levels, and we have therefore changed our routine approach to 600 mg
      daily (following loading doses in each case). We set out to investigate the
      impact of this dose increase on drug levels and potential side-effects. METHODS:
      We undertook a retrospective study of 549 consecutive adult Out-Patient
      Antimicrobial Treatment (OPAT) episodes treated with intravenous teicoplanin.
      RESULTS: Therapeutic teicoplanin levels were more frequently achieved in patients
      treated with 600 mg compared to 400 mg daily (68% vs. 37% respectively, p <
      0.0001), without an increased frequency of potentially toxic levels, defined as
      >60 mg/L (6% vs. 8% respectively, p = 0.4). There was no difference in the
      incidence of neutropaenia, eosinophilia, thrombocytopaenia, acute renal injury or
      treatment cessation in patients treated with the higher teicoplanin dose.
      CONCLUSIONS: In the majority of stable adult patients with normal renal function,
      we advocate a loading regimen (600 mg b.d. for two doses) followed by a 600 mg
      daily teicoplanin dose in order to achieve therapeutic trough levels.

PMID- 24012821
TI  - Development of a childhood obesity prevention programme with a focus on UK South
      Asian communities.
AB  - OBJECTIVE: We report the development of a childhood obesity prevention
      intervention for UK South Asian primary school-aged children, guided by the UK
      Medical Research Council (MRC) framework for complex intervention development and
      evaluation. METHODS: We combined information gained from a literature review,
      stakeholder focus groups, an expert group, review of local resources and mapping
      to the Analysis Grid for Environments Linked to Obesity (ANGELO framework) in an
      intervention development process. The study took place in 2007 in Birmingham, UK.
      RESULTS: Contextual information from the stakeholder focus groups was essential
      for informing intervention development. The expert group defined guiding
      principles for the intervention. Informing intervention design by assessing
      existing local resources addressed intervention sustainability. The use of the
      ANGELO framework ensured a comprehensive environmental approach to intervention
      development. The intervention consisted of two broad processes; increasing
      children's physical activity levels through school, and increasing skills of
      families through activity-based learning. The developed intervention is being
      evaluated in a major study. CONCLUSIONS: The intervention development process has
      resulted in a tailored intervention programme to prevent childhood obesity in UK
      South Asian communities, but also intervention processes that could be applied to
      other communities and tailored to local context.

PMID- 24012822
TI  - Setosphaeria rostrata: Insights from the sequenced genome of Setosphaeria
      turcica.
AB  - Exserohilum rostratum, also known as Setosphaeria rostrata caused an outbreak of
      meningitis in 2012. S. rostrata is known as a minor pathogen of grasses and a
      member of the Dothideomycetes, a group that includes saprobes as well as mild to
      aggressive plant pathogens. A few taxa in this group, such as E. rostratum and
      Cochliobolus lunatus (Curvularia lunata) can be human pathogens, in favorable
      circumstances. Fortunately, human disease caused by E. rostratum is rare.
      However, the increasing number of formerly inconsequential fungi surfacing as
      significant pathogens demands efforts to identify determinants of crossover
      pathogenicity in general, and S. rostrata in particular. Very few genetic and
      molecular data are available for S. rostrata. The first genome sequence for any
      species in the genus Setosphaeria (Setosphaeria turcica) was published this year.
      The literature to date related to virulence determinants of S. rostrata and S.
      turcica to plants and a summary of S. turcica genome features that may inform
      future studies with the human pathogen, S. rostrata, are presented. 

PMID- 24012823
TI  - Theory of interface: category theory, directed networks and evolution of
      biological networks.
AB  - Biological networks have two modes. The first mode is static: a network is a
      passage on which something flows. The second mode is dynamic: a network is a
      pattern constructed by gluing functions of entities constituting the network. In
      this paper, first we discuss that these two modes can be associated with the
      category theoretic duality (adjunction) and derive a natural network structure (a
      path notion) for each mode by appealing to the category theoretic universality.
      The path notion corresponding to the static mode is just the usual directed path.
      The path notion for the dynamic mode is called lateral path which is the
      alternating path considered on the set of arcs. Their general functionalities in
      a network are transport and coherence, respectively. Second, we introduce a
      betweenness centrality of arcs for each mode and see how the two modes are
      embedded in various real biological network data. We find that there is a trade
      off relationship between the two centralities: if the value of one is large then
      the value of the other is small. This can be seen as a kind of division of labor
      in a network into transport on the network and coherence of the network. Finally,
      we propose an optimization model of networks based on a quality function
      involving intensities of the two modes in order to see how networks with the
      above trade-off relationship can emerge through evolution. We show that the trade
      off relationship can be observed in the evolved networks only when the dynamic
      mode is dominant in the quality function by numerical simulations. We also show
      that the evolved networks have features qualitatively similar to real biological
      networks by standard complex network analysis. 

PMID- 24012824
TI  - Probing conformational changes in lipoxygenases upon membrane binding: fine
      tuning by the active site inhibitor ETYA.
AB  - Lipoxygenases (LOXs) are lipid-peroxidizing enzymes that are involved in the
      metabolism of polyunsaturated fatty acids. Their biological activity includes a
      membrane binding process whose molecular details are not completely understood.
      The mechanism of enzyme-membrane interactions is thought to involve
      conformational changes at the level of the protein tertiary structure, and the
      extent of such alterations depends on the degree of structural flexibility of the
      different LOX isoforms. In this study, we have tested the resilience properties
      of a plant and a mammalian LOX, by using high pressure fluorescence measurements
      at different temperatures. The binding of LOXs to the lipid bilayer has been
      characterized using both large and giant unilamellar vesicles and electron
      transfer particles (inner mitochondrial membranes) as model membranes. The data
      indicate that the degree of LOXs' flexibility is strictly dependent on the two
      distinct N- and C-terminal domains that characterize the 3D structure of these
      enzymes. Furthermore, they demonstrate that increasing the rigidity of protein
      scaffolding by the presence of an active site ligand impairs the membrane binding
      ability of LOXs. These findings provide evidence that the amphitropic nature of
      LOXs is finely tuned by the interaction of the substrate with the residues of the
      active site, suggesting new strategies for the design of enzyme inhibitors. 

PMID- 24012825
TI  - IP3 decreases coronary artery tone via activating the BKCa channel of coronary
      artery smooth muscle cells in pigs.
AB  - Large conductance Ca(2+)-activated K(+) channel (BKCa) is a potential target for
      coronary artery-relaxing medication, but its functional regulation is largely
      unknown. Here, we report that inositol trisphosphate (IP3) activated BKCa
      channels in isolated porcine coronary artery smooth muscle cells and by which
      decreased the coronary artery tone. Both endogenous and exogenous IP3 increased
      the spontaneous transient outward K(+) currents (STOC, a component pattern of
      BKCa currents) in perforated and regular whole-cell recordings, which was
      dependent on the activity of IP3 receptors. IP3 also increased the macroscopic
      currents (MC, another component pattern of BKCa currents) via an IP3 receptor-
      and sarcoplasmic Ca(2+) mobilization-independent pathway. In inside-out patch
      recordings, direct application of IP3 to the cytosolic side increased the open
      probability of single BKCa channel in an IP3 receptor-independent manner. We
      conclude that IP3 is an activator of BKCa channels in porcine coronary smooth
      muscle cells and exerts a coronary artery-relaxing effect. The activation of BKCa
      channels by IP3 involves the enhancement of STOCs via IP3 receptors and
      stimulation of MC by increasing the Ca(2+) sensitivity of the channels. 

PMID- 24012826
TI  - Estimation of toxic elements in the samples of different cigarettes and their
      impact on human health of Irish hypertensive consumers.
AB  - BACKGROUND: Cigarette smoking interferes with the metal homeostasis of the human
      body, which plays a crucial role for maintaining the health. A significant flux
      of heavy metals, among other toxins, reaches the lungs through smoking. In the
      present study, the relationship between toxic element (TE) exposure via cigarette
      smoking and hypertension incidence in population living in Dublin, Ireland is
      investigated. METHODS: The different brands of cigarette (filler tobacco, filter
      and ash) consumed by the studied population were analyzed for cadmium (Cd),
      nickel (Ni), and lead (Pb). The concentrations of TEs in biological samples and
      different components of cigarette were measured by inductively coupled plasma
      atomic emission spectrophotometer after microwave-assisted acid digestion. The
      validity and accuracy of the methodology were checked using certified reference
      materials. RESULTS: The filler tobacco of different branded cigarettes contains
      Cd, Ni and Pb concentrations in the ranges of 1.73-2.02, 0.715-1.52 and 0.378
      1.16 MUg/cigarette, respectively. The results of this study showed that the mean
      values of Cd, Ni and Pb were significantly higher in scalp hair and blood samples
      of hypertensive patients in relation to healthy controls, while the difference
      was significant in the case of smoker patients (p<0.001). The levels of all the
      three TEs were 2-3 folds higher in scalp hair and blood samples of non
      hypertensive smoker subjects as compared to nonsmoker controls. CONCLUSION: The
      high exposure of toxic metals as a result of cigarette smoking may be synergistic
      with risk factors associated with hypertension.

PMID- 24012827
TI  - Should acidification of urine be performed before the analysis of calcium,
      phosphate and magnesium in the presence of crystals?
AB  - BACKGROUND: Acidification of urine has been recommended before testing for
      calcium, phosphate, and magnesium. We investigated the necessity of pre
      analytical acidification in both crystallized and non-crystallized urine samples.
      METHODS: From 130 urine samples obtained via routine urine analysis, 65 (50%)
      samples were classified as non-crystallized. All samples were divided into three
      groups: untreated samples, acidified samples with HCl, and acidified samples
      after 1h room-temperature incubation. Urine samples were measured for calcium,
      phosphate, magnesium, and creatinine using Modular P800 and were examined for
      crystals using light microscopy. RESULTS: In crystallized samples, acidified
      samples with 1h incubation had significantly higher Ca/Cr, P/Cr, and Mg/Cr than
      did untreated samples with mean differences of 0.04, 0.03, and 0.01 mg/mg,
      respectively (P<0.001). In acidified samples that were analyzed immediately,
      crystallized samples had lower calcium concentrations than those of acidified
      samples with 1h incubation and a mean difference of 0.21 mg/dl (P = 0.025). None
      of the sample differences which exceeded the critical difference of urinary Ca, P
      and Mg was observed. CONCLUSIONS: Acidification of urine should be performed
      before the measurement of Ca, P, and Mg in the presence of urinary crystals.
      However, the lack of an acidification process does not result in a clinically
      significant change.

PMID- 24012828
TI  - Anatomical MRI templates of tree shrew brain for volumetric analysis and voxel
      based morphometry.
AB  - BACKGROUND: Tree shrews are close relatives of primates, and are increasingly
      used as models in the research of vision, social stress and
      neurological/psychiatric diseases. However, neuroimaging techniques, for example
      magnetic resonance (MR) imaging, are only rarely applied to this species to study
      the structure and function of the brain. A template MR image set, which is
      essential for morphometry/volumetric analysis, of tree shrew brain has been
      lacking in the literature. NEW METHOD: High-resolution anatomical MR images and
      diffusion tensor images of the brain were acquired from male Chinese tree shrews
      (Tupaia belangeri chinensis), and resampled to an isotropic resolution of 200 MUm
      * 200 MUm * 200 MUm. Population-based image templates of tree shrew brain,
      including gray matter/white matter/cerebrospinal fluid probability maps and a
      fractional anisotropy template, were constructed at this spatial resolution, all
      in a reference space. Digital masks of representative anatomical structures,
      including hippocampus, amygdala and cingulum bundle, were created. RESULT: With
      the templates constructed, the volumes of bilateral hippocampus and amygdala were
      measured using a template-facilitated semi-automated approach to be 59.8 +/- 8.3
      and 64.3 +/- 3.4 mm(3), respectively. COMPARISON WITH EXISTING METHOD(S): For the
      first time, high-resolution MR image templates of tree shrew brain were reported.
      The average volume of bilateral hippocampus measured with the template
      facilitated semi-automated approach was found to be similar to the result
      obtained by the much more labor-intensive manual approach. CONCLUSIONS: The MR
      image templates obtained in this study are useful for analyzing neuroimage data
      of tree shrew brain. The templates are freely available to the scientific
      community upon request.

PMID- 24012829
TI  - Assessment of cross-frequency coupling with confidence using generalized linear
      models.
AB  - BACKGROUND: Brain voltage activity displays distinct neuronal rhythms spanning a
      wide frequency range. How rhythms of different frequency interact - and the
      function of these interactions - remains an active area of research. Many methods
      have been proposed to assess the interactions between different frequency
      rhythms, in particular measures that characterize the relationship between the
      phase of a low frequency rhythm and the amplitude envelope of a high frequency
      rhythm. However, an optimal analysis method to assess this cross-frequency
      coupling (CFC) does not yet exist. NEW METHOD: Here we describe a new procedure
      to assess CFC that utilizes the generalized linear modeling (GLM) framework.
      RESULTS: We illustrate the utility of this procedure in three synthetic examples.
      The proposed GLM-CFC procedure allows a rapid and principled assessment of CFC
      with confidence bounds, scales with the intensity of the CFC, and accurately
      detects biphasic coupling. COMPARISON WITH EXISTING METHODS: Compared to existing
      methods, the proposed GLM-CFC procedure is easily interpretable, possesses
      confidence intervals that are easy and efficient to compute, and accurately
      detects biphasic coupling. CONCLUSIONS: The GLM-CFC statistic provides a method
      for accurate and statistically rigorous assessment of CFC.

PMID- 24012830
TI  - Smoking prevalence and its impacts on lung cancer mortality in Sub-Saharan
      Africa: an epidemiological study.
AB  - BACKGROUND: Reliable mortality data are sparse for developing countries.
      Furthermore, risk factor prevalence information is hardly available and thus not
      taken into consideration when estimating mortality. METHODS: The authors used a
      validated, statistical model combined with representative smoking prevalence from
      WHO STEPS surveys to estimate lung cancer mortality for six Sub-Saharan African
      countries (Benin, Malawi, Mozambique, Niger, Sierra Leone, Swaziland). Results
      were compared to a reference database (GLOBOCAN). Using different smoking
      prevalence scenarios, future lung cancer deaths were estimated. RESULTS: The
      prevalence of current moderate smoking among males ranged from 8.7% to 34.6%.
      Prevalence was much lower among females. For all countries considered, our
      mortality estimates were higher than GLOBOCAN estimates that do not consider
      prevalence: Overall, we estimated 2405 lung cancer deaths for 2008 compared to
      531 deaths estimated by GLOBOCAN. Up to 2030, lung cancer deaths are expected to
      increase in general and by over 100% in Benin and Niger. Even under the
      assumption of decrease in smoking prevalence, lung cancer mortality will rise.
      CONCLUSION: On the bases of detailed smoking prevalence information, our findings
      implicate a higher lung cancer burden in low income countries. The epidemiologic
      transition in African low-income countries alludes to the need for targeted
      health prevention efforts.

PMID- 24012831
TI  - Patient knowledge and beliefs as barriers to extending cervical cancer screening
      intervals in Federally Qualified Health Centers.
AB  - OBJECTIVE: Despite guidelines recommending cervical cancer screening intervals be
      extended beyond one year, clinical practice has been slow to change. Patient
      preferences are a potential barrier. In the Centers for Disease Control's
      Cervical Cancer (Cx3) Study at Federally Qualified Health Centers (FQHCs) across
      Illinois, we surveyed patients about screening practices, and assessed beliefs
      regarding lengthening screening intervals. METHOD: We analyzed data from 984 low
      income women in the Cx3 Study (2009-2011). Participants completed a survey
      assessing health history, knowledge about Pap testing, beliefs and intentions
      about extending screening intervals, and demographics. RESULTS: The majority
      reported annual Pap testing (61%), while only 24% reported a 2-3 year screening
      interval (recommendation at time of survey). Misunderstandings about the Pap test
      were prevalent, with over half believing it screened for vaginal, yeast, and
      sexually transmitted infections (58%-72%). Unfavorable beliefs about extending
      screening intervals were common. The majority (57%) indicated that they would not
      wait 3 years to be screened if their physician recommended it, and intentions
      were associated with knowledge about Pap testing. CONCLUSION: Most women reported
      annual cervical cancer screening, and intended to resist longer screening
      intervals. Patients' lack of knowledge and unfavorable beliefs may serve as
      barriers to extending screening intervals.

PMID- 24012832
TI  - Concept mapping applied to the intersection between older adults' outdoor walking
      and the built and social environments.
AB  - OBJECTIVE: For older adults, the ability to navigate walking routes in the
      outdoor environment allows them to remain active and socially engaged,
      facilitating community participation and independence. In order to enhance
      outdoor walking, it is important to understand the interaction of older adults
      within their local environments and the influence of broader stakeholder
      priorities that impact these environments. Thus, we aimed to synthesize
      perspectives from stakeholders to identify elements of the built and social
      environments that influence older adults' ability to walk outdoors. METHOD: We
      applied a concept mapping approach with the input of diverse stakeholders (N=75)
      from British Columbia, Canada in 2012. RESULTS: A seven-cluster map best
      represented areas that influence older adults' outdoor walking. Priority areas
      identified included sidewalks, crosswalks, and neighborhood features. CONCLUSION:
      Individual perceptions and elements of the built and social environments
      intersect to influence walking behaviors, although targeted studies that address
      this area are needed.

PMID- 24012833
TI  - Chaplins of Streptomyces coelicolor self-assemble into two distinct functional
      amyloids.
AB  - Chaplins are small, secreted proteins of streptomycetes that play instrumental
      roles in the formation of aerial hyphae and attachment of hyphae to surfaces.
      Here we show that the purified proteins self-assemble at a water/air interface
      into an asymmetric and amphipathic protein membrane that has an amyloid nature.
      Cryo-tomography reveals that the hydrophilic surface is relatively smooth, while
      the hydrophobic side is highly structured and characterized by the presence of
      small fibrils, which are similar to those observed on the surfaces of aerial
      hyphae. Interestingly, our work also provides evidence that chaplins in solution
      assemble into amyloid fibrils with a distinct morphology. These hydrophilic
      fibrils strongly resemble the structures known to be involved in attachment of
      Streptomyces hyphae to surfaces. These data for the first time show the assembly
      of bacterial proteins into two distinct amyloid structures that have different
      and relevant functions in vivo. 

PMID- 24012835
TI  - Spinal cord maturation and locomotion in mice with an isolated cortex.
AB  - The spinal cord plays a key role in motor behavior. It relays major sensory
      information, receives afferents from supraspinal centers and integrates movement
      in the central pattern generators. Spinal motor output is controlled via
      corticofugal pathways including corticospinal and cortico-subcortical
      projections. Spinal cord injury damages descending supraspinal as well as
      ascending sensory pathways. In adult rodent models, plasticity of the spinal cord
      is thought to contribute to functional recovery. How much spinal cord function
      depends on cortical input is not well known. Here, we address this question using
      Celsr3/Foxg1 mice, in which cortico-subcortical connections (including
      corticospinal tract (CST) and the terminal sensory pathway, the thalamocortical
      tract) are genetically ablated during early development. Although Celsr3/Foxg1
      mice are able to eat, walk, climb on grids and swim, open-field tests showed them
      to be hyperactive. When compared with normal littermates, mutant animals had
      reduced number of spinal motor neurons, with atrophic dendritic trees.
      Furthermore, motor axon terminals were decreased in number, and this was
      confirmed by electromyography. The number of cholinergic, calbindin, and
      calretinin-positive interneurons was moderately increased in the mutant spinal
      cord, whereas that of reelin and parvalbumin-positive interneurons was unchanged.
      As far as we know, our study provides the first genetic evidence that the spinal
      motor network does not mature fully in the absence of corticofugal connections,
      and that some motor function is preserved despite congenital absence of the CST.

PMID- 24012836
TI  - Dominance of P/Q-type calcium channels in depolarization-induced presynaptic FM
      dye release in cultured hippocampal neurons.
AB  - Neurotransmitter release probability is related by high power to the local
      concentration of calcium in presynaptic terminals, which in turn is controlled by
      voltage-gated calcium channels. P/Q- and N-type channels trigger synaptic
      transmission in the majority of neurons of the central nervous system. However,
      whether and under which conditions both channel types act cooperatively or
      independently is still insufficiently understood. Previous studies suggested
      either a dominance of N- or P/Q-type channels, or a synergistic action of both
      channels, depending on the experimental paradigms. Thus, to provide insight into
      the properties of neurotransmitter release in cultured mouse hippocampal neurons,
      we used quantitative analysis of FM dye release from presynaptic boutons induced
      by high potassium membrane depolarization. Increasing extracellular potassium
      concentrations revealed a sigmoid dependence of FM dye release to the stimulation
      strength. Individual and combined application of the P/Q- and N-type channel
      specific blockers omega-agatoxin-IVA and omega-conotoxin-GVIA, respectively,
      allowed us to specifically isolate the contribution of both channel types to
      release triggered with 40 mM KCl. Analysis of the release kinetics and the
      fractional release amplitude demonstrate that, whereas in only 15% of the
      synapses release depended exclusively on P/Q-type channels, the majority of
      synapses (85%) contained both N- and P/Q-type channels. Nevertheless, the
      kinetics of FM dye release in synapses containing both channel types was
      determined by the P/Q-type channels. Together, our data suggest a more direct
      coupling of P/Q-type channels to synaptic release compared to N-type channels,
      which may explain the high prevalence of neurological P/Q-type channelopathies.

PMID- 24012834
TI  - T helper cytokines in dry eye disease.
AB  - Dry eye is an inflammatory disease that results from activation of innate
      inflammatory pathways in resident ocular surface cells, as well as cytokines
      produced by recruited T helper (Th) cells. Cytokines produced by the infiltrating
      Th cells alter the normal cytokine balance on the ocular surface and cause ocular
      surface epithelial pathology. Changes in levels of Th cytokines on the ocular
      surface have been measured in dry eye and the biological effects of these
      cytokines have been documented in experimental culture and mouse model systems.
      The Th2 cytokine IL-13 has a homeostatic role in promoting goblet cell
      differentiation. In contrast, The Th1 cytokine IFN-gamma antagonizes IL-13 and
      promotes apoptosis and squamous metaplasia of the ocular surface epithelia. The
      Th17 cytokine, IL-17 promotes corneal epithelial barrier disruption. The ocular
      surface epithelium expresses receptors to all of these Th cytokines. Therapies
      that maintain normal IL-13 signaling, or suppress IFN-gamma and IL-17 have
      potential for treating the ocular surface disease of dry eye. 

PMID- 24012838
TI  - Tauroursodeoxycholic acid protects retinal neural cells from cell death induced
      by prolonged exposure to elevated glucose.
AB  - Diabetic retinopathy is one of the most frequent causes of blindness in adults in
      the Western countries. Although diabetic retinopathy is considered a vascular
      disease, several reports demonstrate that retinal neurons are also affected,
      leading to vision loss. Tauroursodeoxycholic acid (TUDCA), an endogenous bile
      acid, has proven to be neuroprotective in several models of neurodegenerative
      diseases, including models of retinal degeneration. Since hyperglycemia is
      considered to play a central role in retinal cell dysfunction and degeneration,
      underlying the progression of diabetic retinopathy, the purpose of this study was
      to investigate the neuroprotective effects of TUDCA in rat retinal neurons
      exposed to elevated glucose concentration. We found that TUDCA markedly decreased
      cell death in cultured retinal neural cells induced by exposure to elevated
      glucose concentration. In addition, TUDCA partially prevented the release of
      apoptosis-inducing factor (AIF) from the mitochondria, as well as the subsequent
      accumulation of AIF in the nucleus. Biomarkers of oxidative stress, such as
      protein carbonyl groups and reactive oxygen species production, were markedly
      decreased after TUDCA treatment as compared to cells exposed to elevated glucose
      concentration alone. In conclusion, TUDCA protected retinal neural cell cultures
      from cell death induced by elevated glucose concentration, decreasing mito
      nuclear translocation of AIF. The antioxidant properties of TUDCA might explain
      its cytoprotection. These findings may have relevance in the treatment of
      diabetic retinopathy patients. 

PMID- 24012837
TI  - The control of precerebellar neuron migration by RNA-binding protein Csde1.
AB  - Neuronal migration during brain development sets the position of neurons for the
      subsequent wiring of neural circuits. To understand the molecular mechanism
      regulating the migrating process, we considered the migration of mouse
      precerebellar neurons. Precerebellar neurons originate in the rhombic lip of the
      hindbrain and show stereotypic, long-distance tangential migration along the
      circumference of the hindbrain to form precerebellar nuclei at discrete
      locations. To identify the molecular components underlying this navigation, we
      screened for genes expressed in the migrating precerebellar neurons. As a result,
      we identified the following three genes through the screening; Calm1, Septin 11,
      and Csde1. We report here functional analysis of one of these genes, Csde1, an
      RNA-binding protein implicated in the post-transcriptional regulation of a subset
      of cellular mRNA, by examining its participation in precerebellar neuronal
      migration. We found that shRNA-mediated inhibition of Csde1 expression resulted
      in a failure of precerebellar neurons to complete their migration into their
      prospective target regions, with many neurons remaining in migratory paths.
      Furthermore, those that did reach their destination failed to invade the depth of
      the hindbrain via radial migration. These results have uncovered a crucial role
      of Csde1 in the proper control of both radial and tangential migration of
      precerebellar neurons.

PMID- 24012839
TI  - Enhancement of long-term depression by soluble amyloid beta protein in rat
      hippocampus is mediated by metabotropic glutamate receptor and involves
      activation of p38MAPK, STEP and caspase-3.
AB  - It is reported that the amyloid-beta protein (Abeta)-induced impairments in
      synaptic plasticity coincide with memory decline and dementia. Although Abeta
      induced inhibition of hippocampal long-term potentiation has been intensively
      investigated, the underlying mechanism of Abeta-enhanced long-term depression
      (LTD) is not clear. Here, we report that acute exposure of rat hippocampal slices
      to soluble Abeta-enhanced LTD induced by weak low-frequency stimulation (wLFS;
      1Hz for 3 min, 180 pulses) in granule cells of the dentate gyrus. Application of
      LY341495 (a non-selective Group I/II metrabotropic glumate receptor (mGluR)
      antagonist) completely blocked Abeta-enhanced LTD, whereas D-AP5 (a not selective
      N-methyl-d-aspartate receptor (NMDAR) antagonist) had no effect on Abeta-enhanced
      LTD compared with controls. In addition, Abeta-enhanced LTD was occluded by pre
      application of 3,5-dihydroxyphenylglycine, a Group1 mGluR (mGluR1/5) agonist,
      suggesting Abeta-enhanced LTD depends on mGluR1/5 but not NMDAR. We also report
      here that p38 mitogen-activated protein kinase (p38MAPK) inhibitor SB203580 and
      postsynaptic protein tyrosine phosphatase inhibitors phenylarsine oxide and
      sodium orthovanadate prevented the facilitatory effect of Abeta on LTD.
      Application of striatal-enriched protein tyrosine phosphatase (STEP) activator
      MG132 facilitated induction of LTD by wLFS, but did not block following Abeta
      enhanced LTD induced by another wLFS. On the other hand, Abeta-enhanced LTD
      blocked following MG132-LTD by wLFS, suggesting Abeta-enhanced hippocampal LTD
      involves STEP activation. Application of either non-selective caspase inhibitor Z
      VAD-FMK or caspase-3 selective inhibitor Z-DEVD-FMK prevented Abeta-enhanced LTD.
      However, neither the tumor necrosis factor-alpha converting enzyme inhibitor TAPI
      2 nor the mammalian target of rapamycin inhibitor rapamycin prevented the
      enhancement of Abeta on LTD. Therefore, we conclude that soluble Abeta enhances
      LTD in the hippocampal dentate gyrus region, and the facilitatory effect of Abeta
      on LTD involves mGluR1/5, p38MAPK, STEP and caspase-3 activation.

PMID- 24012840
TI  - Thymoquinone inhibits cell proliferation through regulation of G1/S phase cell
      cycle transition in N-nitrosodiethylamine-induced experimental rat hepatocellular
      carcinoma.
AB  - Dysregulated cell proliferation and tumorigenesis is frequently encountered in
      several cancers including hepatocellular carcinogenesis (HCC). Thus, agents that
      inhibit cell proliferation and restrain hepatic tumorigenesis through cell cycle
      regulation have a beneficial effect in the treatment of hepatocellular
      carcinogenesis. The present study was aimed to investigate the efficacy of
      thymoquinone (TQ), an active compound derived from the medicinal plant Nigella
      sativa, on N-nitrosodiethylamine (NDEA) [0.01% in drinking water for 16 weeks]
      induced hepatocarcinogenesis in experimental rats. After experimental period, the
      hepatic nodules, liver injury markers and tumor markers levels were substantially
      increased in NDEA induced liver tumors in rats. However, TQ (20mg/kg body weight)
      treatment greatly reduced liver injury markers and decreased tumor markers and
      prevented hepatic nodule formation and reduced tumor multiplicity in NDEA induced
      hepatic cancer bearing rats and this was evident from argyrophilic nucleolar
      organizer region (AgNORs) staining. Moreover, the uncontrolled cell proliferation
      was assessed by specific cell proliferative markers [proliferating cell nuclear
      antigen (PCNA) and Ki67] by immunofluorescence, immunoblot and analysis of mRNA
      expression. Simultaneously, we assessed the activity of TQ on G1/S phase cell
      cycle regulation with specific cell cycle proteins (p21(WAF1/CIP1), CDK4, Cyclin
      D1 and Cyclin E) by immunoprecipitation in experimental rats. Treatment with TQ
      significantly reduced the detrimental alterations by abrogating cell
      proliferation, which strongly induced G1/S arrest in cell cycle transition. In
      conclusion, our results suggest that TQ has a potent anti proliferative activity
      by regulating the G1/S phase cell cycle transition and exhibit a beneficial role
      in the treatment of HCC. 

PMID- 24012841
TI  - Studies on glycation of human low density lipoprotein: a functional insight into
      physico-chemical analysis.
AB  - Glycation of biomolecules leads to the establishment of advanced glycation end
      products (AGEs), which have significant role in the pathophysiology of diabetes
      leading to disorders, such as atherosclerosis. Ribose appears to be the most
      reactive among the naturally occurring sugars and contribute significantly to the
      glycation reactions in vivo, however, no report has been published to discuss D
      ribose induced glycation of low density lipoprotein (LDL). The present study
      initially focuses on the glycation of commercially available LDL using different
      concentrations of D-ribose for varied incubation time intervals. The structural
      perturbations induced in LDL were analyzed by UV-vis, fluorescence & circular
      dichroism spectroscopy, and thermal denaturation studies. The ketoamine moieties,
      carbonyl content and HMF content were also quantitated in native and glycated
      LDL. We report structural perturbations, increased carbonyl content, ketoamine
      moieties and HMF content in D-ribose induced glycated LDL (LDL-AGEs) as compared
      to native analogue. These results provide evidence that LDL-AGEs could interfere
      in normal physiological functions and might contribute in the initiation of
      diabetes induced atherosclerosis and other secondary cardiovascular problems in
      diabetic patients. Though ours is a preliminary study, we are sure it would open
      the topic for further studies.

PMID- 24012842
TI  - The role of cyclophilin D in interspecies differences in susceptibility to
      hepatotoxic drug-induced mitochondrial injury.
AB  - Test compound A ((5Z)-6-[(2R,3S)-3-({[(4-Chloro-2
      methylphenyl)sulfonyl]amino}methyl) bicyclo[2.2.2]oct-2-yl]hex-5-enoic acid) was
      withdrawn from premarketing clinical trials due to severe liver injury.
      Intracellular accumulation of lipids (steatosis) has been observed in human
      derived cells and may account for the severe hepatotoxicity. Mitochondrial beta
      oxidation and ketogenesis play a fundamental role in energy homeostasis.
      Mitochondrial dysfunction can therefore cause severe deficiency in fatty acid
      oxidation and apoptosis which finally triggers the hepatocellular injury. Some of
      hepatotoxic drugs (e.g., salicylic acid, diclofenac and troglitazone) are known
      to induce mitochondrial dysfunction. This study therefore examined the effect of
      compound A on the mitochondrial permeability transition (MPT) and membrane
      potential in mitochondria isolated from mouse, rat and monkey livers. The
      incubation of rat and monkey mitochondria energized by succinate in the presence
      of Ca(2+) (20MUM) and compound A (2.5-10MUM) resulted in cyclosporin A (CsA)
      sensitive MPT pore opening and a decline in mitochondrial membrane potential in a
      concentration-dependent manner. However, mouse mitochondria showed low
      susceptibility to compound A-induced dysfunction. Rat mitochondrial expression of
      cyclophilin D (CyPD) was about twice that of mouse mitochondria, but the
      expression levels of other MPT pore proteins (adenine nucleotide translocator and
      voltage-dependent anion channel) were comparable in both species. An assessment
      of the effect of compound A on CyPD knockdown cells demonstrated that
      mitochondrial susceptibility to compound A was attenuated in CyPD knockdown
      cells. These results suggest that an interspecies difference in the
      susceptibility to mitochondrial dysfunction induced by compound A exists as a
      result of species-specific discrepancies in CyPD expression. 

PMID- 24012843
TI  - High-pH-induced flocculation-flotation of the hypersaline microalga Dunaliella
      salina.
AB  - Natural autoflocculation was not observed in a Dunaliella salina hypersaline
      culture and the microalgae did not float without destabilization of the algal
      suspension. High-pH-induced flocculation by sodium hydroxide addition was chosen
      to induce flotation. Recovery efficiencies greater than 90% and concentration
      factors of around 20 were reached. An autoflocculation mechanism, with
      precipitation of magnesium hydroxide, is proposed to explain a sweeping flotation
      of D. salina cells. The influence of the flow rate of sodium hydroxide addition
      was also studied to anticipate the constraints related to the industrialization
      of this process. The flow rate of sodium hydroxide addition had no effect on the
      recovery efficiency and reduced the concentration factor only for abrupt
      injections. Natural increase of culture pH by photosynthetic activity could
      reduce the amount of base consumed. Non-harvested cells remained viable during pH
      increase and could be used as inoculum for a new culture. 

PMID- 24012844
TI  - Coagulation-flocculation of marine Chlorella sp. for biodiesel production.
AB  - Harvesting of marine Chlorella sp. by autoflocculation and flocculation by
      addition of coagulant with pH adjustment was investigated in this study.
      Autoflocculation provided low efficiency. Response surface methodology was
      employed to optimize the coagulant dosage and pH for flocculation. Aluminium
      sulfate and ferric chloride were investigated coagulants. The empirical models
      from RSM are in a good agreement with the experimental results. The optimum
      flocculation was achieved at ferric chloride dosage 143 mg/L, pH 8.1 and settling
      time 40 min. Biomass concentration also presented the significant effect on
      harvesting efficiency. Lipid extracted from marine Chlorella sp. cultivated in
      urea fertilizer medium with hexane as a solvent is suitable to produce biodiesel
      according to it contains high proportion of saturated fatty acids. The crude
      lipid should be purified to remove some impurities before making biodiesel. As
      the free fatty acid content was higher than 1% a two-step biodiesel production is
      recommended.

PMID- 24012845
TI  - Simultaneously improving stability and specificity of cell surface displayed
      glucose dehydrogenase mutants to construct whole-cell biocatalyst for glucose
      biosensor application.
AB  - The improved stability and substrate specificity of cell surface displayed
      glucose dehydrogenase (GDH) mutants by replacing four amino acids from Bacillus
      subtilis by using site-directed mutagenesis was systematically investigated. A
      series of mutated GDHs including E170R/Q252L, V149K/E170R/Q252L,
      E170R/Q252L/G259A and V149K/E170R/Q252L/G259A, were fused to the ice nucleation
      protein for displaying on cell surface of Eschericia coli. Q252L/E170R/V149K,
      Q252L/E170R/G259A and Q252L/E170R/V149K/G259A variants were found stable at a
      wide pH range and shown excellent thermostability. Especially, the
      Q252L/E170R/V149K/G259A mutant showed half-life of ~3.8days at 70  degrees C.
      Q252L/E170R/V149K/G259A variant exhibited the narrowest substrate specificity for
      d-glucose. The whole cell displayed GDH mutant could be cultured in a large scale
      with excellent enzyme activity and productivity. In addition, a sensitive and
      stable electrochemical glucose biosensor can be prepared using the GDH-mutant
      bacteria modified electrode. Thus, the whole cell biocatalysts are promising
      candidates for exploitation in a wide range of industrial applications.

PMID- 24012847
TI  - Optimization of partial nitritation in a continuous flow internal loop airlift
      reactor.
AB  - In the present study, the performance of the partial nitritation (PN) process in
      a continuous flow internal loop airlift reactor was optimized by applying the
      response surface method (RSM). The purpose of this work was to find the optimal
      combination of influent ammonium (NH4(+)-Ninf), dissolved oxygen (DO) and the
      alkalinity/ammonium ratio (Alk/NH4(+)-N) with respect to the effluent nitrite to
      ammonium molar ratio and nitrite accumulation ratio. Based on the RSM results,
      the reduced cubic model and the quadratic model developed for the responses
      indicated that the optimal conditions were a DO content of 1.1-2.1 mg L(-1), an
      Alk/NH4(+)-N ratio of 3.30-5.69 and an NH4(+)-Ninf content of 608-1039 mg L(-1).
      The results of confirmation trials were close to the predictions of the developed
      models. Furthermore, three types of alkali were comparatively explored for use in
      the PN process, and bicarbonate was found to be the best alkalinity source.

PMID- 24012846
TI  - Development of low cost medium for ethanol production from syngas by Clostridium
      ragsdalei.
AB  - The development of a low cost medium for ethanol production is critical for
      process feasibility. Ten media were formulated for Clostridium ragsdalei by
      reduction, elimination and replacement of expensive nutrients. Cost analysis and
      effects of medium components on growth and product formation were investigated.
      Fermentations were performed in 250 mL bottles using syngas (20% CO, 15% CO2, 5%
      H2 and 60% N2). The standard medium M1 cost is $9.83/L, of which 93% is
      attributed to morpholinoethane sulfonic acid (MES) buffer. Statistical analysis
      of the results showed that MES removal did not affect cell growth and ethanol
      production (P>0.05). Based on cells' elemental composition, a minimal mineral
      concentration medium M7 was formulated, which provided 29% higher ethanol yield
      from CO at 3% of the cost compared to medium M1. Ethanol yield from CO in the
      completely defined medium M9 was 36% higher than while at 5% the cost of medium
      M1.

PMID- 24012848
TI  - Generalised modelling approach for anaerobic co-digestion of fermentable
      substrates.
AB  - A general methodology to implement fermentable soluble substrates in the IWA
      Anaerobic Digestion Model No. 1 (ADM1) that extends its application to anaerobic
      co-digestion of multiple substrates is presented. The approach considers the
      fermentation of new soluble substrates, not originally described in ADM1, as
      channelled through mass- and electron-balanced sugar fermentation equivalent
      reactions, and that fermentable substrates are degraded by a generic group of
      fermenters instead of the original ADM1 sugar fermenters. Therefore, no
      additional microbial group state is required. An additional term that modifies
      the ADM1 sugar fermentation kinetics equation was included to account for the
      competition among multiple substrates to be degraded by a particular biomass
      group. The model was validated at pilot scale treating a blend of pig manure
      (soluble fraction), wine and gelatine at mesophilic conditions. Only the ADM1
      acetoclastic ammonia inhibition parameter was calibrated to obtain consistent
      model prediction of gas and liquid composition. 

PMID- 24012850
TI  - Correlation between hemicelluloses-removal-induced hydrophilicity variation and
      the bioconversion efficiency of lignocelluloses.
AB  - In order to establish the correlation between hemicelluloses removal and
      bioconversion efficiency of cellulose, fractionation process with increasing NaOH
      concentration selectively released the hemicellulosic polymers with increasing
      molecular weight and decreasing degree of substitution. Not only the initial
      hydrolysis rates also the concentrations of glucose and ethanol were
      significantly enhanced from 5.93 and 8.39 g/L to the range of 8.67-9.60 g/L and
      11.53-13.71 g/L after alkaline treatment, respectively. However, the maximum
      conversions of cellulose to glucose (61.9%) and ethanol (64.6%) were achieved as
      33.0% hemicelluloses was still remained. Excluding the negligible effect on the
      crystal transformation of cellulose, the improvement of bioconversion efficiency
      was resulted from the synergetical effects of surface exposure, multi-layers
      collapse and the hydrophilic property of the cellulosic substrate. It is critical
      task to balance these factors by the partial removal of hemicellulosic component,
      not complete.

PMID- 24012849
TI  - Orthogonal test design for optimization of lipid accumulation and lipid property
      in Nannochloropsis oculata for biodiesel production.
AB  - In order to improve the property of Nannochloropsis oculata as biodiesel
      feedstock, a L9(3(4)) orthogonal test on limited nitrogen supplementation (0,
      0.22 and 0.44 mmol N L(-1)), high iron concentration (1.2*10(-2), 1.2*10(-1) and
      1.2 mmol Fe L(-1)) and culture temperature (10, 20 and 30  degrees C) was
      conducted to select the most effective combinational measurement. Results showed
      that microalgae displayed the highest total lipid content (60.44+/-0.68%), the
      highest neutral lipid proportion (90.74+/-0.18%), the highest lipid yield
      (152.70+/-7.40 mg L(-1)) and the largest cetane number (CN, 64.34+/-0.13) under
      different combined conditions. There were significant interaction among nitrogen
      supplementation, iron concentration and culture temperature on the lipid yield
      and CN of N. oculata. Nitrogen supplementation, followed by iron concentration
      and temperature orderly, was the most influential factor in lipid yield. It is
      therefore suggested that the combination of 0.44 mmol N L(-1), 1.2*10(-1) mmol Fe
      L(-1) and 20  degrees C was the best measurement for improving the property of N.
      oculata as biodiesel feedstock.

PMID- 24012851
TI  - Landfill leachate treatment as measured by nitrogen transformations in
      stabilization ponds.
AB  - The treatment performance and nitrogen mass balance of a pilot-scale landfill
      leachate treatment system was evaluated. The system was comprised of a series of
      three ponds and a rock filter and was fed a continuous flow (200 L d(-1)) during
      111 weeks. Three different operational conditions were investigated: conventional
      operation (stage I), aeration (stage II) and aeration/recirculation (stage III).
      The system was able to treat landfill leachate with soluble chemical oxygen
      demand and ammonia removal between 35-82% and 75-99%, respectively, and the
      highest removal occurred during the recirculation stage. The nitrogen balance was
      calculated using total nitrogen applied load and the main transformation
      processes within the ponds. The main form of nitrogen transformation/removal was
      by dead/inert algae settle (64-79%), followed by volatilization (12-27%) and
      algae assimilation (1-6%). Nitrification/denitrification occurred in only stage
      II. Analyses of the phytoplankton community showed that the Chlamydomonas genera
      were dominant in the photosynthetic ponds.

PMID- 24012852
TI  - Autonomous functions of murine thyroid hormone receptor TRalpha and TRbeta in
      cochlear hair cells.
AB  - Thyroid hormone acts on gene transcription by binding to its nuclear receptors
      TRalpha1 and TRbeta. Whereas global deletion of TRbeta causes deafness, global
      TRalpha-deficient mice have normal hearing thresholds. Since the individual roles
      of the two receptors in cochlear hair cells are still unclear, we generated mice
      with a hair cell-specific mutation of TRalpha1 or deletion of TRbeta using the
      Cre-loxP system. Hair cell-specific TRbeta mutant mice showed normal hearing
      thresholds but delayed BK channel expression in inner hair cells, slightly
      stronger outer hair cell function, and slightly reduced amplitudes of auditory
      brainstem responses. In contrast, hair cell-specific TRalpha mutant mice showed
      normal timing of BK channel expression, slightly reduced outer hair cell
      function, and slightly enhanced amplitudes of auditory brainstem responses. Our
      data demonstrate that TRbeta-related deafness originates outside of hair cells
      and that TRalpha and TRbeta play opposing, non-redundant roles in hair cells. A
      role for thyroid hormone receptors in controlling key regulators that shape
      signal transduction during development is discussed. Thyroid hormone may act
      through different thyroid hormone receptor activities to permanently alter the
      sensitivity of auditory neurotransmission. 

PMID- 24012853
TI  - Manifestations of coronary arterial injury during catheter ablation of atrial
      fibrillation and related arrhythmias.
AB  - BACKGROUND: The prevalence and clinical consequences of coronary arterial injury
      in a large series of patients undergoing radiofrequency ablation (RFA) of atrial
      fibrillation (AF) are unknown. OBJECTIVE: The purpose of this study was to
      describe the frequency and clinical consequences of coronary arterial injury in a
      large series of patients undergoing catheter ablation of AF and postablation
      atrial tachycardia. METHODS: The medical records of 5,709 consecutive patients
      undergoing RFA of AF were reviewed. Heart specimens were also dissected to
      analyze the course of the coronary arteries. RESULTS: Arterial injury occurred in
      8 patients (0.14%). Three patients developed ventricular fibrillation (VF) due to
      occlusion of the distal or proximal circumflex (Cx) artery related to RFA in the
      distal coronary sinus (CS) or base of the LA appendage, respectively. Two VF
      patients underwent stenting. Five patients developed acute sinus node (SN)
      dysfunction. In 4/5 patients, the culprit site was subjacent to the SN artery
      (per computed tomography) coursing over the anterior LA (n = 3) or the septal RA
      (n = 1). Two patients required a permanent pacemaker. In the heart specimens, the
      SN artery, after its origin from the proximal Cx artery, coursed along the
      anterior LA. Also, the proximal Cx artery was found in the atrioventricular
      groove underneath the base of the LA appendage. CONCLUSION: Clinically apparent
      injury to the coronary arteries during LA ablation for AF is rare. However, it
      may be associated with potentially life-threatening ventricular arrhythmias and
      acute SN dysfunction requiring permanent pacing. The culprit sites seem to be in
      the distal coronary sinus and the anterior LA, and correlate well with the course
      of the coronary arteries in pathologic specimens. Vigilance and low-power
      settings are important in minimizing the risk of arterial injury.

PMID- 24012854
TI  - Ultrastructure, functional morphology and evolution of recto-canal epidermal
      glands in Myriapoda.
AB  - In Chilopoda, solitary epidermal glands are composed of a couple of cells only.
      These glands are highly abundant on the entire body surface and are distributed
      throughout the single-layered epidermis. Some authors provided more or less
      comprehensive observations on the structure of epidermal glands of specific
      chilopod taxa. However, no information is hitherto available on the
      ultrastructural diversity of these glands. Furthermore, potential homologies of
      these chilopod epidermal glands and of their characteristic cellular components
      remain unknown. Based on our results, we are now able to distinguish two types of
      epidermal glands in Chilopoda that can be clearly distinguished by their
      structure and the course of their conducting canal: recto-canal epidermal glands
      (rceg) and flexo-canal epidermal glands (fceg). In the present paper, we focus on
      the rceg. We examined the ultrastructural organization of these glands in the
      head region and on the anterior trunk segments of various representatives of the
      five extant chilopod orders by light- and electron-microscopy. According to our
      terminology, rceg consist of up to five different cell types including: a) distal
      canal cells, b) proximal canal cells, c) intermediary cells, and d) two different
      types of secretory cells. Intermediary and canal cells form a common conducting
      canal. The rceg may taxon-specifically differ in relative size and subcellular
      architecture, but all have the following features in common: 1) a wide
      distribution on various body regions among all five chilopod subtaxa, 2) the
      straight, broad and locally dilated conducting canal surrounded by closely packed
      microvilli or microvilliform infoldings around the apex of the canal cell(s), and
      3) the tendency to aggregate to form compound glandular organs of massive size
      and complexity. Tricellular glandular units established by three different cell
      types are observed in Scutigeromorpha and Geophilomorpha, whereas four cell types
      constitute rceg in Lithobiomorpha and Craterostigmomorpha. Five different cell
      types per glandular unit are found only in Scolopendromorpha. The partial
      cuticularization of the lower part of the conducting canal formed by the
      intermediary cell, as found in Chilopoda, differs from the pattern described for
      equivalent euarthropod epidermal glands, as for instance in Hexapoda. Their wide
      distribution in Chilopoda and Progoneata makes it likely that tricellular rceg
      were at least present in the last common ancestor of the Myriapoda. Concerning
      Chilopoda, the evolution of highly diverse rceg is well explained on the basis of
      the Pleurostigmophora concept. Glands of the recto-canal type are also found in
      other arthropods. The paper discusses cases where homology of rceg and also fceg
      may be assumed beyond Myriapoda and briefly evaluates the potentials and the
      still-to-be-solved issues prior to use them as an additional character system to
      reconstruct the phylogeny of the Euarthropoda. 

PMID- 24012856
TI  - Measurement of C-terminal cross-linking telopeptide of type I collagen:
      Evaluation of a new automated assay.

PMID- 24012855
TI  - A bioassay for Lafora disease and laforin glucan phosphatase activity.
AB  - OBJECTIVES: Lafora disease is a rare yet invariably fatal form of progressive
      neurodegenerative epilepsy resulting from mutations in the phosphatase laforin.
      Several therapeutic options for Lafora disease patients are currently being
      explored, and these therapies would benefit from a biochemical means of assessing
      functional laforin activity following treatment. To date, only clinical outcomes
      such as decreases in seizure frequency and severity have been used to indicate
      success of epilepsy treatment. However, these qualitative measures exhibit
      variability and must be assessed over long periods of time. In this work, we
      detail a simple and sensitive bioassay that can be used for the detection of
      functional endogenous laforin from human and mouse tissue. DESIGN AND METHODS: We
      generated antibodies capable of detecting and immunoprecipitating endogenous
      laforin. Following laforin immunoprecipitation, laforin activity was assessed via
      phosphatase assays using para-nitrophenylphosphate (pNPP) and a malachite green
      based assay specific for glucan phosphatase activity. RESULTS: We found that
      antibody binding to laforin does not impede laforin activity. Furthermore, the
      malachite green-based glucan phosphatase assay used in conjunction with a rabbit
      polyclonal laforin antibody was capable of detecting endogenous laforin activity
      from human and mouse tissues. Importantly, this assay discriminated between
      laforin activity and other phosphatases. CONCLUSIONS: The bioassay that we have
      developed utilizing laforin antibodies and an assay specific for glucan
      phosphatase activity could prove valuable in the rapid detection of functional
      laforin in patients to which novel Lafora disease therapies have been
      administered.

PMID- 24012857
TI  - The reference intervals for HE4, CA125 and ROMA in healthy female with
      electrochemiluminescence immunoassay.
AB  - OBJECTIVES: Human epididymis protein 4 (HE4) is a tumor marker in diagnosing
      ovarian cancer. Together with cancer antigen 125 (CA125) and the risk of ovarian
      malignancy algorithm (ROMA) score, it can improve sensitivity and specificity.
      There are no reports about the serum HE4 reference intervals (RIs) with
      electrochemiluminescence immunoassay (ECLIA). The RI of ROMA hasn't been
      established yet. In this study, we establish the RIs for serum HE4, CA125 and
      ROMA in healthy Chinese female with ECLIA. METHODS: Serum HE4 and CA125
      concentrations in healthy female (age ranged from 21 to 81 years) were
      simultaneously measured with ECLIA on Roche Cobas E601 system. The RIs were
      determined following CLSI C28-A3 guidelines using a nonparametric method.
      RESULTS: The upper limits of the 95% percentile intervals were 82.62 pmol/L for
      HE4, 30.91 U/mL for CA125 and 19.27 for ROMA. The reference limits for HE4, CA125
      and ROMA were 65.87 pmol/L, 32.23 U/mL, 13.14 for premenopausal women, and 90.76
      pmol/L, 27.52 U/mL, 25.46 for postmenopausal women respectively. CONCLUSION: We
      established the RIs for serum HE4, CA125 and ROMA with ECLIA in healthy Chinese
      female. It provided a reference for clinical and laboratory studies.

PMID- 24012859
TI  - Introduction of a new scaling approach for particle size reduction in toothed
      rotor-stator wet mills.
AB  - A new scaling approach has been demonstrated for particle size reduction of an
      active pharmaceutical ingredient (API) in toothed rotor-stator wet mills for a
      wide range of wet milling conditions and scales. Compound A was crystallized by a
      cooling crystallization protocol in ethanol and wet milled with 2 types of lab
      scale mills and 1 pilot plant mill. The particle size was analyzed by FBRM
      (focused beam reflectance measurement), static light scattering and optical
      microscopy. The correlation between particle size and the energy input
      calculations, tailored for the toothed rotor-stator wet mill, had R(2)=0.90 on a
      logarithmic plot. The new scaling approach forms the basis to correlate API
      particle size to energy input in toothed rotor-stator wet mills by accounting for
      wet mill tooth configuration and geometry, rotor tip speed and the probabilistic
      effects of collision such as shear frequency and slurry residence time. 

PMID- 24012860
TI  - A novel approach to oral iron delivery using ferrous sulphate loaded solid lipid
      nanoparticles.
AB  - Iron (Fe) loaded solid lipid nanoparticles (SLN's) were formulated using stearic
      acid and iron absorption was evaluated in vitro using the cell line Caco-2 with
      intracellular ferritin formation as a marker of iron absorption. Iron loading was
      optimised at 1% Fe (w/w) lipid since an inverse relation was observed between
      initial iron concentration and SLN iron incorporation efficiency. Chitosan (Chi)
      was included to prepare chitosan coated SLN's. Particle size analysis revealed a
      sub-micron size range (300.3+/-31.75 nm to 495.1+/-80.42 nm), with chitosan
      containing particles having the largest dimensions. As expected, chitosan (0.1%,
      0.2% and 0.4% w/v) conferred a net positive charge on the particle surface in a
      concentration dependent manner. For iron absorption experiments equal doses of Fe
      (20 MUM) from selected formulations (SLN-FeA and SLN-Fe-ChiB) were added to Caco
      2 cells and intracellular ferritin protein concentrations determined. Caco-2 iron
      absorption from SLN-FeA (583.98+/-40.83 ng/mg cell protein) and chitosan
      containing SLN-Fe-ChiB (642.77+/-29.37 ng/mg cell protein) were 13.42% and 24.9%
      greater than that from ferrous sulphate (FeSO4) reference (514.66+/-20.43 ng/mg
      cell protein) (p<=0.05). We demonstrate for the first time preparation,
      characterisation and superior iron absorption in vitro from SLN's, suggesting the
      potential of these formulations as a novel system for oral iron delivery.

PMID- 24012858
TI  - Subsequent memory effect in intracranial and scalp EEG.
AB  - Successful memory encoding is marked by increases in 30-100Hz gamma-band activity
      in a broad network of brain regions. Activity in the 3-8Hz theta band has also
      been shown to modulate memory encoding, but this effect has been found to vary in
      direction across studies. Because of the diversity in memory tasks, and in
      recording and data-analytic methods, our knowledge of the theta frequency
      modulations remains limited. The difference in the directionality of these theta
      effects could arise from a distinction between global cortical and deeper
      subcortical effects. To address this issue, we examined the spectral correlates
      of successful memory encoding using intracranial EEG recordings in neurosurgical
      patients and scalp EEG recordings in healthy controls. We found significant theta
      (3-8Hz) power modulations (both increases and decreases) and high gamma (44
      100Hz) power increases in both samples of participants. These results suggest
      that (1) there are two separate theta mechanisms supporting memory success, a
      broad theta decrease present across both the cortex and hippocampus as well as a
      theta power increase in the frontal cortex, (2) scalp EEG is capable of resolving
      high frequency gamma activity, and (3) iEEG theta effects are likely not the
      result of epileptic pathology. 

PMID- 24012861
TI  - Effect of permeation enhancers on transdermal delivery of fluoxetine: in vitro
      and in vivo evaluation.
AB  - The aim of this study was to investigate the feasibility of transdermal
      fluoxetine (FX) delivery. The effects of chemical forms (base or salt) and
      permeation enhancers on in vitro skin permeation of FX were assessed using
      hairless mouse, rat and human cadaver skin. The optimized formulations from the
      in vitro studies were then evaluated in an in vivo pharmacokinetic study in rats.
      The in vitro skin permeation studies suggested that the FX base (FXB) and
      isopropyl myristate (IPM)-limonene mixture could be suitable for transdermal
      delivery of FX. The permeation parameters of FX through human cadaver skin were
      well correlated with that through hairless mouse and rat skin, suggesting that
      these animal models can be used for predicting the permeability of FX through
      human skin. After transdermal administration of FX with IPM or the IPM-limonene
      mixture to rats, the mean steady-state plasma concentration (Css) was 66.20 or
      77.55 ng/mL, respectively, which was maintained over 36 h and had a good
      correlation with the predicted Css from the in vitro data. These in vitro and in
      vivo data demonstrated that permeation enhancers could be a potential strategy
      for transdermal delivery of FX.

PMID- 24012862
TI  - Entamoeba histolytica P-glycoprotein (EhPgp) inhibition, induce trophozoite
      acidification and enhance programmed cell death.
AB  - Programmed cell death (PCD) is induced in Entamoeba histolytica by a variety of
      stimuli in vitro and in vivo. In mammals, intracellular acidification serves as a
      global switch for inactivating cellular processes and initiates molecular
      mechanisms implicated in the destruction of the genome. In contrast,
      intracellular alkalinization produced by P-glycoprotein overexpression in
      multidrug-resistant cells has been related to apoptosis resistance. Our previous
      studies showed that overexpression of E. histolytica P-glycoprotein (PGP) altered
      chloride-dependent currents and triggered trophozoite swelling, the reverse
      process of cell shrinkage produced during PCD. Here we showed that antisense
      inhibition of PGP expression produced a synchronous death of trophozoites and the
      enhancement of biochemical and morphological characteristics of PCD induced by
      G418. The nucleus was contracted, and the nuclear membrane was disrupted.
      Moreover, chromatin was extensively fragmented. Ca(2+) concentration was
      increased, while the intracellular pH (ipH) was acidified. In contrast, PGP
      overexpression prevented intracellular acidification and circumvented the
      apoptotic effect of G418. 

PMID- 24012863
TI  - Overview of Drosophila immunity: a historical perspective.
AB  - The functional analysis of genes from the model organism Drosophila melanogaster
      has provided invaluable information for many cellular and developmental or
      physiological processes, including immunity. The best-understood aspect of
      Drosophila immunity is the inducible humoral response, first recognized in 1972.
      This pioneering work led to a remarkable series of findings over the next 30
      years, ranging from the identification and characterization of the antimicrobial
      peptides produced, to the deciphering of the signalling pathways activating the
      genes that encode them and, ultimately, to the discovery of the receptors sensing
      infection. These studies on an insect model coincided with a revival of the field
      of innate immunity, and had an unanticipated impact on the biomedical field.

PMID- 24012864
TI  - Stress at encoding, context at retrieval, and children's narrative content.
AB  - Research concerning the relations between stress and children's memory has been
      primarily correlational and focused on memory volume and accuracy. In the current
      study, we experimentally manipulated 7- and 8-year-olds' and 12- to 14-year-olds'
      experienced stress during a to-be-remembered event to examine the effects of
      stress on the content of their memory. We further manipulated the degree of
      interviewer support at retrieval to determine whether it moderated the effects of
      stress at encoding on memory. Children's age, gender, stress at encoding, and
      interviewer support all influenced the type of information included in their
      narrative reports. Most notably, across ages, children who experienced a more
      stressful event but were questioned in a supportive manner provided the largest
      ratio of terms representing internal states such as those about cognitions and
      emotions. Results suggest that how children process past events may be influenced
      by both the nature of the event itself and the context within which it is
      recalled. 

PMID- 24012865
TI  - Novel biotinylated chitosan-graft-polyethyleneimine copolymer as a targeted non
      viral vector for anti-EGF receptor siRNA delivery in cancer cells.
AB  - The major impediments to develop an efficient non-viral siRNA-mediated gene
      silencing method, as a therapeutic approach, are the low cellular uptake and
      intracellular delivery and release of non-viral vectors. To overcome these
      problems, designing a proper vector with high transfection efficiency is
      obviously under scrutiny of various studies. The present study, evaluate a novel
      biotinylated chitosan-graft-polyethyleneimine (Bio-Chi-g-PEI) copolymer as an
      appropriate non-viral vector for targeted delivery of siRNA to cancer cells. The
      composition of the synthesized Bio-Chi-g-PEI copolymer was thoroughly
      characterized using (1)H NMR and FTIR spectroscopy, besides the hydroxyazobenzene
      2-carboxylic acid (HABA) assay. In vitro cytotoxicity assay of the Bio-Chi-g-PEI
      copolymers was performed by MTT assay. Cytotoxicity evaluations indicated that
      the new copolymer was markedly less toxic than PEI 25KD. Physicochemical
      properties of the Bio-Chi-g-PEI/siRNA complexes such as complex stability, size,
      zeta potential, and their morphology at various weight ratios, investigated by
      appropriate methods, revealed the suitability of the complexes for the
      transfection. The efficient cellular internalization of the complexes for HeLa
      and OVCAR-3 cells in culture media was confirmed by intracellular tracking of the
      prepared complexes using confocal laser scanning microscopy and Cy3-labeled anti
      epidermal growth factor receptor siRNA. Finally, evaluation of the transfection
      efficiency and gene silencing by flow cytometry and real-time polymerase chain
      reaction highlighted the significantly higher efficiency of transfection and
      silencing for biotinylated copolymer compared with the PEI 25KD and non
      biotinylated copolymer.

PMID- 24012866
TI  - Tailored beads made of dissolved cellulose--investigation of their drug release
      properties.
AB  - In the frame of this work, we have investigated drug entrapping and release
      abilities of new type of porous cellulose beads (CBs) as a spherical matrix
      system for drug delivery. For that purpose, CBs prepared with three different
      methods were used as drug carriers and three compounds, anhydrous theophylline
      (Thp), riboflavin 5'-phosphate sodium (RSP) and lidocaine hydrochloride
      monohydrate (LiHCl) were used as model drug substances. The loading procedure was
      carried out by immersing swollen empty beads into the solutions of different
      concentrations of model drugs. The morphology of empty and loaded beads was
      examined using a field emission scanning electron microscopy (FE-SEM). Near
      infrared (NIR) imaging was performed to identify the drug distributions on and
      within the loaded CBs. The drug amount incorporated into CBs was examined
      spectrophotometrically and in vitro drug release studies were performed to
      determine the drug release rates. The results of FE-SEM and chemical NIR imaging
      analyses revealed that incorporated drug were distributed on the surface and but
      also within the internal structure of the CBs. Physical properties of CBs and
      solubility of model drugs had effect on loading efficacy. Also, the drug release
      rates were controlled by solubility of model drugs (diffusion controlled
      release). In conclusion, CBs from dissolved cellulose show promise in achieving
      controlled drug delivery. 

PMID- 24012867
TI  - Inhibition of surface crystallisation of amorphous indomethacin particles in
      physical drug-polymer mixtures.
AB  - Surface coverage may affect the crystallisation behaviour of amorphous materials.
      This study investigates crystallisation inhibition in powder mixtures of
      amorphous drug and pharmaceutical excipients. Pure amorphous indomethacin (IMC)
      powder and physical mixtures thereof with Eudragit((r)) E or Soluplus((r)) in
      3:1, 1:1 and 1:3 (w/w) ratios were stored at 30  degrees C and 23 or 42% RH.
      Samples were analysed during storage by X-ray powder diffraction,
      thermogravimetric analysis, differential scanning calorimetry, and scanning
      electron microscopy (SEM). IMC Eudragit((r)) mixtures showed higher physical
      stability than pure IMC whereas IMC Soluplus((r)) mixtures did not. Water uptake
      was higher for mixtures containing Soluplus((r)) than for amorphous IMC or IMC
      Eudragit((r)) mixtures. However, the Tg of amorphous IMC was unaffected by the
      presence (and nature) of polymer. SEM revealed that Eudragit((r)) particles
      aggregated on the surface of IMC particles, whereas Soluplus((r)) particles did
      not. The drug particles developed multiple crystallites at their surface with
      subsequent crystal growth. The intimate contact between the surface agglomerated
      Eudragit((r)) particles and drug is believed to inhibit crystallisation through
      reduced IMC surface molecular mobility. Polymer particles may also mechanically
      hinder crystal growth outwards from the surface. This work highlights the
      importance of microparticulate surface coverage of amorphous drug particles on
      their stability.

PMID- 24012869
TI  - A double mutation in AGXT gene in families with primary hyperoxaluria type 1.
AB  - Primary hyperoxaluria type 1 (PH1) is a severe autosomal recessive inherited
      disorder of glyoxylate metabolism caused by mutations in the AGXT gene on
      chromosome 2q37.3 that encodes the hepatic peroxisomal enzyme alanine:glyoxylate
      aminotransferase. These mutations are found throughout the entire gene and cause
      a wide spectrum of clinical severity. Rare in Europe, PH1 is responsible for 13%
      of the end stage renal failure in the Tunisian child. In the present work, we
      identified the double mutation c.32C>T (Pro11Leu) and c.731T>C (p.Ile244Thr) in
      AGXT gene in five unrelated Tunisian families with PH1 disease. Our results
      provide evidence regarding the potential involvement of c.32C>T, originally
      described as common polymorphism, on the resulting phenotype. We also reported an
      extreme intrafamilial heterogeneity in clinical presentation of PH1. Despite the
      same genetic background, the outcome of the affected members differs widely. The
      significant phenotypic heterogeneity observed within a same family, with a same
      genotype, suggests the existence of relevant modifier factors. 

PMID- 24012868
TI  - Effects of Pro12Ala polymorphism in peroxisome proliferator-activated receptor
      gamma2 gene on metabolic syndrome risk: a meta-analysis.
AB  - BACKGROUND: Associations between peroxisome proliferator-activated receptor
      gamma2 (PPARgamma2) gene polymorphism and metabolic syndrome risk remained
      controversial and ambiguous. Thus, we performed a meta-analysis to assess the
      association between Pro12Ala polymorphism in PPARgamma2 gene and metabolic
      syndrome susceptibility. METHODS: An electronic literature search was conducted
      on Medline, OVID, Cochrane Library database, and the China National Knowledge
      Internet up to March 2013. Odds ratios (ORs) with 95% confidence intervals (CIs)
      were used to calculate the strength of association in the fixed or random effects
      model. RESULTS: Ten studies involving a total of 4456 cases and 10343 controls
      were included in this meta-analysis. No statistical evidence of association was
      found between Pro12Ala polymorphism and metabolic syndrome risk in all genetic
      models (homozygote model: OR=0.83, 95% CI=0.62-1.12; heterozygote model: OR=1.04,
      95% CI=0.94-1.14; dominant model: OR=1.02, 95% CI=0.93-1.12; recessive model:
      OR=0.83, 95% CI=0.62-1.11). No statistical evidence of significant association
      was observed when stratified by ethnicity, definition of metabolic syndrome,
      source of control groups and quality score of the selected articles. All in all,
      the results did not support a major role of the Pro12Ala variant of the
      PPARgamma2 gene in metabolic syndrome risk. CONCLUSIONS: This meta-analysis
      suggested that the effect of Pro12Ala polymorphism in PPARgamma2 gene may not be
      related to metabolic syndrome as an entity. However, Pro12Ala may affect the
      single component of metabolic syndrome. A large, well designed study is required
      to more adequately assess the role for Pro12Ala polymorphism on metabolic
      syndrome.

PMID- 24012870
TI  - Gene Wiki Reviews: marrying crowdsourcing with traditional peer review.

PMID- 24012871
TI  - f57f4.4p::gfp as a fluorescent reporter for analysis of the C. elegans response
      to bacterial infection.
AB  - Host defense mechanisms are multi-layered and involve constitutive as well as
      inducible components. The dissection of these complex processes can be greatly
      facilitated using a reporter gene strategy with a transparent animal. In this
      study, we use Caenorhabditis elegans as a model host and introduce a new pathogen
      inducible fluorescent reporter involving the promoter of f57f4.4, a gene encoding
      a putative component of the glycocalyx. We show that this reporter construct does
      not respond to heavy metal or hypertonic environments, but is specifically and
      locally induced in the intestine upon Photorhabus luminescens and Pseudomonas
      aeruginosa infections. We further demonstrate that its upregulation requires live
      pathogens as well as elements of the nematode p38 MAP kinase and TGF-beta
      pathways. In addition to introducing a new tool for the study of the interactions
      between C. elegans and a pathogen, our results suggest a role for the glycocalyx
      in gut immunity.

PMID- 24012873
TI  - Binding and discerning interactions of PTP1B allosteric inhibitors: novel
      insights from molecular dynamics simulations.
AB  - The alpha7 helix is either disordered or missing in the three co-crystal
      structures of allosteric inhibitors with protein tyrosine phosphatase 1B (PTP1B).
      It was modeled in each complex using the open form of PTP1B structure and studied
      using molecular dynamics (MD) simulations for 25 ns. B-factor analysis of the
      residues sheds light on its disordered nature in the co-crystal structures.
      Further, the ability of inhibitors to act as allosteric inhibitor was studied and
      established using novel hydrogen bond criteria. The MD simulations were utilized
      to determine the relative importance of electrostatic and hydrophobic component
      in to the binding of inhibitors. It was revealed that the hydrophobic
      interactions predominantly drive the molecular recognition of these inhibitors.
      Per residue energy decomposition analysis attributed dissimilar affinities of
      three inhibitors to the several hydrogen bonds and non-bonded interactions. Among
      the secondary structure elements that surround the allosteric site, helices
      alpha6, alpha7 and loop alpha6-alpha7 were notorious in providing variable
      affinities to the inhibitors. A novel hydrophobic pocket lined by the alpha7
      helix residues Val287, Asn289 and Trp291 was identified in the allosteric site.
      This study provides useful insights for the rational design of high affinity
      PTP1B allosteric inhibitors.

PMID- 24012872
TI  - Design of e-pharmacophore models using compound fragments for the trans-sialidase
      of Trypanosoma cruzi: screening for novel inhibitor scaffolds.
AB  - Chagas' is a fatal disease that affects millions of people worldwide. The lack of
      safe and effective treatments for Chagas' highlights the need for the discovery
      of new drugs to fight the disease. Trypanosoma cruzi, the parasitic cause of
      Chagas' disease, synthesizes a trans-sialidase (TcTS) enzyme responsible for the
      transfer of sialic acids from the host cell surface to glycoconjugates on the
      parasitic cell surface. TcTS has no human analogs and is vital to the life cycle
      of T. cruzi, making TcTS an important enzyme for drug design against Chagas'
      disease. We use fragment docking to generate various e-pharmacophore hypotheses
      depicting protein residues important for ligand binding. Virtual screening of the
      ZINC Clean Leads database with more than 4 million compounds using the e
      pharmacophore models found 82 potential inhibitors of TcTS. Molecular dynamics
      and free energy of binding calculations were used to rank the compounds based on
      their affinity for TcTS. Two compounds-ZINC13359679 and ZINC02576132-were found
      to be the most promising lead candidates for TcTS inhibition, and their binding
      modes are analyzed in detail. 

PMID- 24012874
TI  - Life cycle assessment of water reuse systems in an industrial park.
AB  - The rapid development of industrial parks in China has resulted in large resource
      consumption and pollutant emissions, especially freshwater use and wastewater
      discharge. Water reuse has attracted much attention from governments because of
      its potential to conserve freshwater and reduce pollutant emissions. However,
      water reuse usually means adding advanced treatment which consumes chemicals,
      materials and energy. Is the water reuse beneficial for the environment from a
      life cycle perspective? To answer this question, we quantified the environmental
      impacts of reusing treated wastewater at industrial parks under different
      scenarios through a comparative life-cycle assessment (LCA). Four scenarios are
      assessed: wastewater is treated and discharged, 20% and 99% of wastewater is
      treated and reused as industrial process water, and treated wastewater is used
      for horticulture. Inventory data were mainly obtained from a facility which
      manages the wastewater treatment and reuse system of an industrial park in
      Jiangsu Province. Environmental impacts were evaluated using the CML2001 method
      built into the GaBi version 4.3 database. The results show the water reuse is
      beneficial and the reuse rate significantly affects environmental performance of
      the system. It is also found that using the reclaimed water for higher value
      applications results in larger environmental credit. Decision makers in water
      management should consider both water quantity and quality and associated
      environmental impacts for different water reuse applications. 

PMID- 24012875
TI  - Neural mechanism of central inhibition during physical fatigue: a
      magnetoencephalography study.
AB  - Central inhibition plays an important role in physical performance during
      physical fatigue. We tried to clarify the neural mechanism of central inhibition
      during physical fatigue using the magnetoencephalography (MEG) and a classical
      conditioning technique. Twelve right-handed volunteers participated in this
      study. Participants underwent MEG recording during the imagery of maximum grips
      of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue
      inducing maximum handgrip trials were performed for 10 min; the metronome sounds
      were started 5 min after the beginning of the handgrip trials. We used metronome
      sounds as conditioned stimuli and maximum handgrip trials as unconditioned
      stimuli to cause central inhibition. The next day, MEG recording during the
      imagery of maximum grips of the right hand guided by metronome sounds were
      measured for 10 min. Levels of the fatigue sensation in the right hand and
      sympathetic nerve activity on the second day were significantly higher than those
      on the first day. In the right dorsolateral prefrontal cortex (Brodmann's area
      46), the alpha-band event-related desynchronization (ERD) of the second MEG
      session relative to the first session with the time window of 200 to 300 ms after
      the onset of handgrip cue sounds was identified. The ERD level in this brain
      region was positively associated with the change in subjective level of right
      hand fatigue after the conditioning session and was negatively associated with
      that of the sympathetic nerve activity. We demonstrated that the right
      dorsolateral prefrontal cortex is involved in the neural substrates of central
      inhibition during physical fatigue.

PMID- 24012877
TI  - Task-dependent response conflict monitoring and cognitive control in anterior
      cingulate and dorsolateral prefrontal cortices.
AB  - Previous experience affects our behavior in terms of adjustments. It has been
      suggested that the conflict monitor-controller system implemented in the
      prefrontal cortex plays a critical role in such adjustments. Previous studies
      suggested that there exists multiple conflict monitor-controller systems
      associated with the level of information (i.e., stimulus and response levels). In
      this study, we sought to test whether different types of conflicts occur at the
      same information processing level (i.e., response level) are independently
      processed. For this purpose, we designed a task paradigm to measure two different
      types of response conflicts using color-based and location-based conflict stimuli
      and measured the conflict adaptation effects associated with the two types of
      conflicts either independently (i.e., single conflict conditions) or
      simultaneously (i.e., a double-conflict condition). The behavioral results
      demonstrated that performance on current incongruent trials was faster only when
      the preceding trial was the same type of response conflict regardless of whether
      they included a single- or double-conflict. Imaging data also showed that
      anterior cingulate and dorsolateral prefrontal cortices operate in a task
      specific manner. These findings suggest that there may be multiple monitor
      controller loops for color-based and location-based conflicts even at the same
      response level. Importantly, our results suggest that double-conflict processing
      is qualitatively different from single-conflict processing although double
      conflict shares the same sources of conflict with two single-conflict conditions.

PMID- 24012876
TI  - BOLD response to working memory not related to cortical thickness during early
      adolescence.
AB  - BACKGROUND: Significant cortical thinning and neural resource allocation changes
      emerge during adolescence; however, little is known of how morphometric changes
      influence neural response to cognitive demands. This study used a novel
      multimodal imaging registration technique to examine the relationship between
      brain structure and function during adolescence. METHODS: 156 healthy 12-14 year
      olds (44% female) participants underwent structural and functional magnetic
      resonance imaging. Cortical surface reconstruction was performed via FreeSurfer,
      and neural activation was measured from a blood oxygen level dependent (BOLD)
      contrast during visual working memory (VWM) via AFNI. AFNI Surface Mapper aligned
      segmented volumetric and functional datasets to a common template space.
      Hierarchical linear regressions determined the effect of cortical thickness on
      VWM BOLD contrast in brain regions that activated during the VWM task,
      controlling for age, pubertal development, gender, IQ, and intracranial volume.
      RESULTS: Power analyses suggest this study was able to detect small effect sizes.
      However, in no region was cortical thickness related to BOLD activation (ps>.01;
      R(2)Delta<.02). Gender did not moderate effects. CONCLUSIONS: Cortical thickness,
      although variable across individuals, was not related to BOLD response,
      suggesting that structural and functional maturation do not have the same
      developmental trajectory during early adolescence. These findings are important,
      as imaging studies that report group differences in regards to cortical thickness
      should not necessarily assume co-occurring behavioral or functional changes. The
      methodology used in this study could be of interest to other developmental
      neuroimaging researchers using multimodal imaging to understand adolescent brain
      development.

PMID- 24012878
TI  - HIV protease inhibitor Lopinavir induces apoptosis of primary effusion lymphoma
      cells via suppression of NF-kappaB pathway.
AB  - Primary effusion lymphoma (PEL) is a non-Hodgkin lymphoma that occurs
      predominantly in patients with advanced AIDS. In this study, we examined the
      effect of HIV protease inhibitors, Lopinavir (LPV), Ritonavir (RTV) and Darunavir
      (DRV) on PEL cell lines in vitro and in vivo. LPV and RTV, but not DRV induced
      caspase-dependent apoptosis and suppressed NF-kappaB activity by inhibiting IKK
      phosphorylation in PEL cells. In a PEL xenograft mouse model, LPV significantly
      inhibited the growth and invasion of PEL cells. These results suggest that LPV
      may have promise for the treatment and prevention of PEL, which occurs in
      HIV/AIDS patients. 

PMID- 24012879
TI  - Notch-signalling is required for head regeneration and tentacle patterning in
      Hydra.
AB  - Local self-activation and long ranging inhibition provide a mechanism for setting
      up organising regions as signalling centres for the development of structures in
      the surrounding tissue. The adult hydra hypostome functions as head organiser.
      After hydra head removal it is newly formed and complete heads can be
      regenerated. The molecular components of this organising region involve Wnt
      signalling and beta-catenin. However, it is not known how correct patterning of
      hypostome and tentacles are achieved in the hydra head and whether other signals
      in addition to HyWnt3 are needed for re-establishing the new organiser after head
      removal. Here we show that Notch-signalling is required for re-establishing the
      organiser during regeneration and that this is due to its role in restricting
      tentacle activation. Blocking Notch-signalling leads to the formation of
      irregular head structures characterised by excess tentacle tissue and aberrant
      expression of genes that mark the tentacle boundaries. This indicates a role for
      Notch-signalling in defining the tentacle pattern in the hydra head. Moreover,
      lateral inhibition by HvNotch and its target HyHes are required for head
      regeneration and without this the formation of the beta-catenin/Wnt dependent
      head organiser is impaired. Work on prebilaterian model organisms has shown that
      the Wnt-pathway is important for setting up signalling centres for axial
      patterning in early multicellular animals. Our data suggest that the integration
      of Wnt-signalling with Notch-Delta activity was also involved in the evolution of
      defined body plans in animals. 

PMID- 24012880
TI  - The hemagglutinin mutation E391K of pandemic 2009 influenza revisited.
AB  - Phylogenetic analyses based on small to moderately sized sets of sequential data
      lead to overestimating mutation rates in influenza hemagglutinin (HA) by at least
      an order of magnitude. Two major underlying reasons are: the incomplete lineage
      sorting, and a possible absence in the analyzed sequences set some of key missing
      ancestors. Additionally, during neighbor joining tree reconstruction each
      mutation is considered equally important, regardless of its nature. Here we have
      implemented a heuristic method optimizing site dependent factors weighting
      differently 1st, 2nd, and 3rd codon position mutations, allowing to extricate
      incorrectly attributed sub-clades. The least squares regression analysis of
      distribution of frequencies for all mutations observed on a partially
      disentangled tree for a large set of unique 3243 HA sequences, along all
      nucleotide positions, was performed for all mutations as well as for non
      equivalent amino acid mutations - in both cases demonstrating almost flat
      gradients, with a very slight downward slope towards the 3'-end positions. The
      mean mutation rates per sequence per year were 3.83*10(-4) for the all mutations,
      and 9.64*10(-5) for the non-equivalent ones. 

PMID- 24012881
TI  - Evaluating measures of semantic similarity and relatedness to disambiguate terms
      in biomedical text.
AB  - INTRODUCTION: In this article, we evaluate a knowledge-based word sense
      disambiguation method that determines the intended concept associated with an
      ambiguous word in biomedical text using semantic similarity and relatedness
      measures. These measures quantify the degree of similarity or relatedness between
      concepts in the Unified Medical Language System (UMLS). The objective of this
      work is to develop a method that can disambiguate terms in biomedical text by
      exploiting similarity and relatedness information extracted from biomedical
      resources and to evaluate the efficacy of these measure on WSD. METHOD: We
      evaluate our method on a biomedical dataset (MSH-WSD) that contains 203 ambiguous
      terms and acronyms. RESULTS: We show that information content-based measures
      derived from either a corpus or taxonomy obtain a higher disambiguation accuracy
      than path-based measures or relatedness measures on the MSH-WSD dataset.
      AVAILABILITY: The WSD system is open source and freely available from
      http://search.cpan.org/dist/UMLS-SenseRelate/. The MSH-WSD dataset is available
      from the National Library of Medicine http://wsd.nlm.nih.gov.

PMID- 24012882
TI  - Inhibition of influenza hemagglutinin with the antiviral inhibitor arbidol using
      a proteomics based approach and mass spectrometry.
AB  - A proteomics gel electrophoresis based approach has been applied to study the
      effect of arbidol on the proliferation of influenza virus in vitro through
      quantitation of hemagglutinin levels. An arbidol concentration of 20MUg/ml was
      required to achieve a 50% reduction in virus proliferation and hemagglutinin
      levels. The use of a MALDI mass spectrometry approach to study the binding of
      arbidol to influenza hemagglutinin revealed it bound solely to residues 104-120
      of the HA2 subunit, a region known to contain an arbidol resistance mutation.
      Parallel molecular docking results revealed that this binding site was favoured
      in which the arbidol molecule binds in two possible orientations approximately
      180 degrees  to one another at HA2 residues 118-123. The combined studies support
      the recognized potential of arbidol as an effective and targeted antiviral agent
      against the influenza virus. 

PMID- 24012883
TI  - Rectal endoscopic submucosal dissection made easy: a solution to the retraction
      problem.

PMID- 24012884
TI  - Allergen exposure induces inflammation and affects adiponectin levels in adipose
      tissue.
AB  - This study investigates whether allergen exposure elevates the risk of diabetes
      or cardiovascular diseases using acute OVA (Ovalbumin) allergen exposure model.
      We hypothesize that exposure to allergen can induce adipose tissue inflammation
      and affect adiponectin levels. An intranasal challenge with OVA male C57BL/6 mice
      was performed at dose of 6.25, 12.5, 25, 50 and 100MUg, and compared to which
      challenge with PBS (phosphate buffered saline). Results showed that acute OVA
      exposure did not only cause airway inflammation in study mice, but also decreased
      serum adiponectin levels with a dose-response effect. When examining the gonadal
      adipose tissues, there was no significantly difference of adiponectin mRNA in OVA
      challenged mice compared to those PBS challenged, but lower inguinal adiponectin
      mRNA expression was found compared to those PBS-challenged, and had a good
      relationship with the serum adiponectin. Inguinal adipose tissues of OVA
      challenged mice, had significantly lower adipose tissue weight, and higher TNF
      alpha expression without statistical significance. Our data indicate that acute
      OVA exposure appears to affect the characteristics of adipose tissues, and change
      the adiponectin levels in serum and adipose tissues. Allergen exposure may be
      considered a potential risk factor for presenting diabetes or cardiovascular
      diseases. 

PMID- 24012885
TI  - Angiogenesis, mediated by miR-21, is involved arsenite-induced carcinogenesis.
AB  - Evidence for arsenite-induced lung cancer in humans is strong, but the molecular
      mechanisms by which arsenite causes cancer remain to be established. Angiogenesis
      is a fundamental characteristic of cancer and is necessary in its multi-step
      progression. In this investigation, the mechanism for arsenite-induced
      angiogenesis was evaluated. Tumors formed from human bronchial epithelial (HBE)
      cells transformed by arsenite developed new blood vessels, which were prevented
      by the knockdown of miR-21, and cultures of human umbilical vein endothelial
      cells (HUVEC) exposed to arsenite developed endothelial tubes, a characteristic
      of angiogenesis. Also found in transformed HBE cells were up-regulation of a
      microRNA, miR-21, and increased levels of vascular endothelial growth factor
      (VEGF), which promotes angiogenesis. Down-regulation of miR-21 in these cells
      inhibited the arsenite-induced increases of VEGF levels. Thus, we conclude that
      arsenite induces tumor angiogenesis through processes mediated by miR-21. 

PMID- 24012886
TI  - Methamphetamine inhibits voltage-gated potassium currents in NG108-15 cells:
      possible contribution of large-conductance calcium-activated potassium channels.
AB  - Methamphetamine (MA), a highly abused amphetamine-like psychostimulant, has
      surged in popularity worldwide in the last decade. Repeated MA exposure has been
      shown to affect the alternative splice variant expression of large conductance
      Ca(2+)-activated K(+) (BK) channels. It remains unclear whether MA affects BK
      channel activity. The present study investigated the effects of MA on BK channels
      in NG108-15 mouse neuroblastoma*rat glioma hybrid cells using whole-cell and cell
      attached patch clamp techniques. In whole-cell recordings, the macroscopic K(+)
      outward currents were inhibited by MA with an EC50 of 146MUM, but not affected by
      dopamine (DA). It implies that DA is not involved in the effects of MA on K(+)
      outward currents. In cell-attached patches, MA significantly decreased BK channel
      activity. Moreover, MA significantly decreased the BK channel opener NS1619
      evoked whole-cell K(+) outward currents and BK channel activity. Finally, the
      effect of MA on membrane potential was examined by current-clamp configuration.
      MA caused membrane depolarization and application of NS1619 returned the
      depolarized potential to resting value. These findings suggest that MA might act
      as an inhibitor of BK channels, and thereby increase the neuronal excitability
      and enhance neurotransmitter release. 

PMID- 24012888
TI  - Sertoli cell dedifferentiation in human cryptorchidism and gender reassignment
      shows similarities between fetal environmental and adult medical treatment
      estrogen and antiandrogen exposure.
AB  - Studies over the last years show an increase in testicular cancer, hypospadias
      and cryptorchidism in industrial countries, leading to the concept of testicular
      dysgenesis syndrome (TDS). It is hypothesized that TDS is caused by estrogen and
      antiandrogen exposure during fetal life, accompanied by incomplete maturation of
      testicular Sertoli cells (SC). However, it is not known if SC disruption is a
      primary cause or a response to fetal Leydig cell testosterone production changes.
      To determine if SC differentiation is directly affected by estrogens, we compared
      SC maturation between adult gender reassignment cases exposed to estrogen and
      antiandrogen therapy, and those of typical TDS in adult cryptorchidism. We found
      similar expression of immature SC markers M2A antigen, inhibin bodies and Anti
      Mullerian Hormone, and the absence of maturation marker androgen receptor in SC
      of both types of patients. These data supports the occurrence of true SC
      dedifferentiation caused by estrogen exposure in adult humans. Our data also
      suggests that SC maturation is directly disrupted in TDS. 

PMID- 24012887
TI  - Paraoxonase-2 (PON2) in brain and its potential role in neuroprotection.
AB  - Paraoxonase 2 (PON2) is a member of a gene family which also includes the more
      studied PON1, as well as PON3. PON2 is unique among the three PONs, as it is
      expressed in brain tissue. PON2 is a lactonase and displays anti-oxidant and anti
      inflammatory properties. PON2 levels are highest in dopaminergic regions (e.g.
      striatum), are higher in astrocytes than in neurons, and are higher in brain and
      peripheral tissues of female mice than male mice. At the sub-cellular level, PON2
      localizes primarily in mitochondria, where it scavenges superoxides. Lack of PON2
      (as in PON2(-/-) mice), or lower levels of PON2 (as in male mice compared to
      females) increases susceptibility to oxidative stress-induced toxicity. Estradiol
      increases PON2 expression in vitro and in vivo, and provides neuroprotection
      against oxidative stress. Such neuroprotection is not present in CNS cells from
      PON2(-/-) mice. Similar results are also found with the polyphenol quercetin.
      PON2, given its cellular localization and antioxidant and anti-inflammatory
      actions, may represent a relevant enzyme involved in neuroprotection, and may
      represent a novel target for neuroprotective strategies. Its differential
      expression in males and females may explain gender differences in the incidence
      of various diseases, including neurodevelopmental, neurological, and
      neurodegenerative diseases. 

PMID- 24012889
TI  - Neuroprotective effects of liquiritigenin isolated from licorice roots on
      glutamate-induced apoptosis in hippocampal neuronal cells.
AB  - The progressive death of neurons following exposure to high concentrations of
      glutamate leads to loss of learning and memory and pathogenesis of
      neurodegenerative disorders. Therefore, identification of drugs that protect
      against glutamate-mediated neuronal cell death is a good strategy for prevention
      and treatment of neurodegenerative diseases. In this study, we isolated
      liquiritigenin, an active compound found in licorice roots, by column
      chromatography and examined its protective effects against glutamate-mediated
      apoptotic stimuli in a mouse hippocampus-derived neuronal cell line (HT22 cells).
      Cell viability was significantly recovered following treatment with 50MUM
      liquiritigenin up to 77.50+/-1.93% over the control (100.00+/-5.62%), whereas
      cell viability following 5mM glutamate treatment was decreased to 52.52+/-4.82%.
      Liquiritigenin effectively reduced glutamate-induced early apoptosis through
      inhibition of Ca(2+) influx, intracellular reactive oxygen species (ROS)
      production, and lipid peroxidation. In addition, the levels of Bcl-2 and full
      length Bid were protected, and that of mitochondrial Bax was reduced by
      liquiritigenin. Liquiritigenin suppressed not only the release of apoptosis
      inducing factor (AIF), but also activation of mitogen-activated protein kinases
      (MAPKs) such as p38, extracellular signal-regulated kinase (ERK), and c-Jun N
      terminal kinase (JNK). Therefore, the active component in licorice roots,
      liquiritigenin, might facilitate development of drug leads for neurodegenerative
      disorders. 

PMID- 24012891
TI  - Using (222)Rn as a tracer of geodynamical processes in underground environments.
AB  - Radon levels in two old mines in San Luis, Argentina, were measured and analyzed,
      with the aim to assess the potential use of this radioactive noble gas as a
      tracer of geological processes in underground environments. La Carolina gold mine
      and Los Condores tungsten mine are today used as tourism mines. CR-39 nuclear
      track detectors were used for this purpose. Measurements were performed during
      both winter and summer seasons. The findings show that in these environments,
      significant radon concentrations are subject to large seasonal fluctuations, due
      to the strong dependence on natural ventilation with the outside temperature
      variations. For both mines, higher concentration values of (222)Rn were observed
      in summer than in winter; with an extreme ratio of 2.5 times between summer and
      winter seasons for Los Condores mine. The pattern of radon transport inside La
      Carolina mine revealed, contrary to what was believed, that this mine behaves as
      a system with two entrances located at different levels. However, this feature
      can only be observed in the winter season, when there is a marked difference
      between the inside and outside temperatures of the mine. In the case of Los
      Condores mine, the radon concentration pattern distribution is principally
      established by air current due to chimney-effect in summer and winter seasons. In
      both cases, the analyses of radon pattern distribution appear as a good method to
      trace air currents, and then localize unknown ducts, fissures or secondary
      tunnels in subterranean environments. 

PMID- 24012890
TI  - Growing Right Onto Wellness (GROW): a family-centered, community-based obesity
      prevention randomized controlled trial for preschool child-parent pairs.
AB  - Growing Right Onto Wellness (GROW) is a randomized controlled trial that tests
      the efficacy of a family-centered, community-based, behavioral intervention to
      prevent childhood obesity among preschool-aged children. Focusing on parent-child
      pairs, GROW utilizes a multi-level framework, which accounts for macro (i.e.,
      built-environment) and micro (i.e., genetics) level systems that contribute to
      the childhood obesity epidemic. Six hundred parent-child pairs will be randomized
      to a 3-year healthy lifestyle intervention or a 3-year school readiness program.
      Eligible children are enrolled between ages 3 and 5, are from minority
      communities, and are not obese. The principal site for the GROW intervention is
      local community recreation centers and libraries. The primary outcome is
      childhood body mass index (BMI) trajectory at the end of the three-year study
      period. In addition to other anthropometric measurements, mediators and
      moderators of growth are considered, including genetics, accelerometry, and diet
      recall. GROW is a staged intensity intervention, consisting of intensive,
      maintenance, and sustainability phases. Throughout the study, parents build
      skills in nutrition, physical activity, and parenting, concurrently forming new
      social networks. Participants are taught goal-setting, self-monitoring, and
      problem solving techniques to facilitate sustainable behavior change. The GROW
      curriculum uses low health literacy communication and social media to communicate
      key health messages. The control arm is administered to both control and
      intervention participants. By conducting this trial in public community centers,
      and by implementing a family-centered approach to sustainable healthy childhood
      growth, we aim to develop an exportable community-based intervention to address
      the expanding public health crisis of pediatric obesity. 

PMID- 24012892
TI  - Reduction of clarithromycin and sulfamethoxazole-resistant Enterococcus by pilot
      scale solar-driven Fenton oxidation.
AB  - The presence of pathogenic antibiotic-resistant bacteria in aquatic environments
      has become a health threat in the last few years. Their presence has increased
      due to the presence of antibiotics in wastewater effluents, which are not
      efficiently removed by conventional wastewater treatments. As a result there is a
      need to study the possible ways of removal of the mixtures of antibiotics present
      in wastewater effluents and the antibiotic-resistant bacteria, which may also
      spread the antibiotic resistance genes to other bacterial populations. In this
      study the degradation of a mixture of antibiotics i.e. sulfamethoxazole and
      clarithromycin, the disinfection of total enterococci and the removal of those
      resistant to: a) sulfamethoxazole, b) clarithromycin and c) to both antibiotics
      have been examined, along with the toxicity of the whole effluent mixture after
      treatment to the luminescent aquatic bacterium Vibrio fischeri. Solar Fenton
      treatment (natural solar driven oxidation) using Fenton reagent doses of 50 mg L(
      1) of hydrogen peroxide and 5 mg L(-1) of Fe(3+) in a pilot-scale compound
      parabolic collector plant was used to examine the disinfection and antibiotic
      resistance removal efficiency in different aqueous matrices, namely distilled
      water, simulated and real wastewater effluents. There was a faster complete
      removal of enterococci and of antibiotics in all aqueous matrices by applying
      solar Fenton when compared to photolytic treatment of the matrices.
      Sulfamethoxazole was more efficiently degraded than clarithromycin in all three
      aqueous matrices (95% removal of sulfamethoxazole and 70% removal of
      clarithromycin in real wastewater). The antibiotic resistance of enterococci
      towards both antibiotics exhibited a 5-log reduction with solar Fenton in real
      wastewater effluent. Also after solar Fenton treatment, there were 10 times more
      antibiotic-resistant enterococci in the presence of sulfamethoxazole than in the
      presence of clarithromycin. Finally, the toxicity of the treated wastewater to V.
      fischeri remained very low throughout the treatment time.

PMID- 24012893
TI  - Highly pathogenic Salmonella Pomona was first isolated from the exotic red-eared
      slider (Trachemys scripta elegans) in the wild in China: Implications for public
      health.
AB  - Salmonella Pomona, a highly pathogenic serotype, can cause severe human
      salmonellosis, especially in children. Turtles and other reptiles are reservoirs
      for S. Pomona, and these cold-blooded animals remain a source of human Salmonella
      infections. Since the 1980s, this serotype has become a significant public health
      concern because of the increasing number of cases of S. Pomona infection in
      humans. To date, outbreaks of Salmonella Pomona infection in humans have mainly
      occurred in the United States, with some in other countries (e.g. Belgium,
      Germany, Canada), and most of the infections in humans were associated with
      turtles and other reptiles. In China, S. Pomona was first isolated from the feces
      of an infant in Shanghai in 2000, and two further cases of S. Pomona infection in
      humans were later found in Guangzhou. No one knew the source of S. Pomona in
      China. In this study, for the first time we isolated S. Pomona from free-living
      exotic red-eared sliders in the wild in China. Salmonella serotype (S. Pomona)
      was isolated from 16 turtle samples. The total carrying rate of S. Pomona in the
      collected red-eared sliders was 39% (n = 41) overall: 40% (n = 25) in juveniles
      and 38% (n = 16) in adult turtles. This study suggests that the widespread exotic
      red-eared sliders may impact on public health and ecosystems of China by
      transmitting S. Pomona. Additional steps should be considered by the governments
      and public health agencies to prevent the risk of turtle-associated Salmonella
      infections in humans in China.

PMID- 24012894
TI  - Emergence and fate of cyclic volatile polydimethylsiloxanes (D4, D5) in municipal
      waste streams: release mechanisms, partitioning and persistence in air, water,
      soil and sediments.
AB  - Siloxane use in consumer products (i.e., fabrics, paper, concrete, wood, adhesive
      surfaces) has significantly increased in recent years due to their excellent
      water repelling and antimicrobial characteristics. The objectives of this study
      were to evaluate the release mechanisms of two siloxane compounds,
      octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5), which
      have been detected both at landfills and wastewater treatment plants, estimate
      persistence times in different media, and project release quantities over time in
      relation to their increasing use. Analyses were conducted based on fate and
      transport mechanisms after siloxanes enter waste streams. Due to their high
      volatility, the majority of D4 and D5 end up in the biogas during decomposition.
      D5 is about ten times more likely to partition into the solid phase (i.e., soil,
      biosolids). D5 concentrations in the wastewater influent and biogas are about 16
      times and 18 times higher respectively, in comparison to the detected levels of
      D4. 

PMID- 24012895
TI  - Seasonal and diel variations of ammonia and methane emissions from a naturally
      ventilated dairy building and the associated factors influencing emissions.
AB  - Understanding seasonal and diel variations of ammonia (NH3) and methane (CH4)
      emissions from a naturally ventilated dairy (NVD) building may lead to develop
      successful control strategies for reducing emissions throughout the year. The
      main objective of this study was to quantify seasonal and diel variations of NH3
      and CH4 emissions together with associated factors influencing emissions.
      Measurements were carried out with identical experimental set-up to cover three
      winter, spring and summer seasons, and two autumn seasons in the years 2010,
      2011, and 2012. The data from 2010 and 2011 were used for developing emission
      prediction models and the data from 2012 were used for model validation. The
      results showed that NH3 emission varied seasonally following outside temperature
      whereas CH4 emission did not show clear seasonal trend. Diel variation of CH4
      emission was less pronounced than NH3. The average NH3 and CH4 emissions between
      6a.m. and 6p.m. were 66% and 33% higher than the average NH3 and CH4 emissions
      between 6p.m. and 6a.m., respectively for all seasons. The significant
      relationships (P<0.0001) between NH3 and influencing factors were found including
      outside temperature, humidity, wind speed and direction, hour of the day and day
      of the year. The significant effect (P<0.0001) of climate factors, hours of the
      day and days of the year on CH4 emission might be directly related to activities
      of the cows. 

PMID- 24012896
TI  - Temporal variation of aerosol optical depth and associated shortwave radiative
      forcing over a coastal site along the west coast of India.
AB  - Optical characterization of aerosol was performed by assessing the columnar
      aerosol optical depth (AOD) and angstrom wavelength exponent (alpha) using data
      from the Microtops II Sunphotometer. The data were collected on cloud free days
      over Goa, a coastal site along the west coast of India, from January to December
      2008. Along with the composite aerosol, the black carbon (BC) mass concentration
      from the Aethalometer was also analyzed. The AOD0.500 MUm and angstrom wavelength
      exponent (alpha) were in the range of 0.26 to 0.7 and 0.52 to 1.33, respectively,
      indicative of a significant seasonal shift in aerosol characteristics during the
      study period. The monthly mean AOD0.500 MUm exhibited a bi-modal distribution,
      with a primary peak in April (0.7) and a secondary peak in October (0.54),
      whereas the minimum of 0.26 was observed in May. The monthly mean BC mass
      concentration varied between 0.31 MUg/m(3) and 4.5 MUg/m(3), and the single
      scattering albedo (SSA), estimated using the OPAC model, ranged from 0.87 to
      0.97. Modeled aerosol optical properties were used to estimate the direct aerosol
      shortwave radiative forcing (DASRF) in the wavelength range 0.25 MUm4.0 MUm. The
      monthly mean forcing at the surface, at the top of the atmosphere (TOA) and in
      the atmosphere varied between -14.1 Wm(-2) and -35.6 Wm(-2), -6.7 Wm(-2) and 
      13.4 Wm(-2) and 5.5 Wm(-2) to 22.5 Wm(-2), respectively. These results indicate
      that the annual SSA cycle in the atmosphere is regulated by BC (absorbing
      aerosol), resulting in a positive forcing; however, the surface forcing was
      governed by the natural aerosol scattering, which yielded a negative forcing.
      These two conditions neutralized, resulting in a negative forcing at the TOA that
      remains nearly constant throughout the year.

PMID- 24012897
TI  - Assessment of the use of sediment fences for control of erosion and sediment
      phosphorus loss after potato harvesting on sloping land.
AB  - In humid temperate areas, after harvest of potatoes, it is difficult to prevent
      soil erosion and diffuse pollution. In some autumn weather conditions, in-field
      mitigation such as cultivation or sowing are not possible, while edge of field
      measures can be costly and inflexible. We have assessed the potential of modified
      sediment fences, widely used on building sites, for erosion mitigation post
      harvest of potato crops. Field scale assessments were conducted on fields in the
      Lunan catchment, eastern Scotland. Sediment retention was estimated by two
      methods: a topographic survey method using a hand held Real Time Kinematic Global
      Positioning System (RTK-GPS), and direct measurement of sediment depth using a
      graduated cane. In the 2010/11 trial the main fence comprised 70 m of entrenched
      fine mesh (0.25 mm) and coarser mesh (4mm) fabric pinned to a contour fence near
      the base of the field. This retained an estimated 50.9 m(3) (80.2 tonnes) of
      sediment, with weighted mean total P (TP) content of 0.09 % in the<2mm soil
      fraction. In the 2011/12 trial, the main 146 m fence was of intermediate mesh
      size (1.2mm). The fence was partitioned into nine upslope plots, with 3
      replicates of each of 3 cultivation methods: T1 (full grubbing--a light, tined
      cultivator), T2 (partial grubbing) and T3 (no grubbing). Average plot slopes
      ranged from 9.9 to 11.0 %. The amounts of TP accumulating as sediment at the
      fences were: 9.3 (sd = 7.8), 11.8 (sd = 10.2) and 25.7 (sd = 5.8)kg P/ha of
      upslope plot for the T1, T2 and T3 treatments respectively.

PMID- 24012898
TI  - Gas-phase tropospheric chemistry of 2,3,7,8-tetrafuorinated dibenzo-p-dioxin.
AB  - Growing attention has been devoted to understanding the formation and destruction
      of polyfluorinated dibenzo-p-dioxins (PFDDs). High-accuracy molecular orbital
      calculations have been performed to investigate the tropospheric oxidation
      reaction of 2,3,7,8-tetrafuorinated dibenzo-p-dioxin (TFDD) initiated by OH
      radical, NO3 radical and O3. The rate constant of TFDD reaction triggered by the
      OH radical, NO3 radical and O3 is about 2.30 * 10(-11)cm(3) molecule(-l) s(-l),
      3.18 * 10(-13)cm(3) molecule(-l) s(-l), and 3.30 * 10(-19)cm(3) molecule(-l) s(
      l), respectively. OH radical is the major gas phase tropospheric sink for TFDD.
      Once TFDD-OH intermediates are produced in the initial reactions, they can react
      with tropospheric O2 subsequently to generate peroxy radical isomers. The TFDD-OH
      O2 can further react with tropospheric NO via isomerization or combination,
      resulting that the dioxin ring will be ruptured completely. This study can serve
      as a template for tropospheric degradation of the gaseous PFDDs, which is
      beneficial for assessing their tropospheric behaviors.

PMID- 24012899
TI  - A preliminary investigation on nanohorn toxicity in marine mussels and
      polychaetes.
AB  - Single walled carbon nanohorns (SWCNHs) are a black nanoscale spherical aggregate
      of cylindrical tubes of graphitic carbon which differ from nanotubes in their
      "horn-like" shape. Their peculiar structure makes them one of the best
      electronconductors at a nanoscale level. Although not commercially exploited,
      their rapid environmental diffusion is expected to rise significantly in the next
      few years. Therefore, we appraised the ecotoxicology of SWCNH powders by taking
      into account the ecological role of the two species that were deployed in
      exposure experiments: polychaetes, Hediste diversicolor, and mussels, Mytilus
      galloprovincialis. Adult mussels and polychaetes were exposed to three SWCNH
      concentrations: 1, 5, and 10 mg L(-1) and acute effects were measured after 24
      and 48 h. Sub-lethal effects were estimated at level of physiological functions
      such as digestion in mussels (i.e. variations in lysosomal parameters and
      lipofuscin content) and the antioxidant system in both species (i.e. glutathione
      peroxidase activity and malondialdehyde content). SWCNH suspension in sea water
      was also characterised, highlighting the formation of aggregates the size of
      which was related to SWCNH concentrations and their resident time in the medium.
      The results showed that SWCNH affected the oxidative and lysosomal systems on the
      hepatopancreas and led to lysosomal alterations on haemocytes in mussels. The
      biological responses were less clear in polychaetes. This preliminary
      investigation highlighted the need of focusing future research efforts on
      possible physiological impairments caused by long-term exposure to SWCNHs in
      marine species.

PMID- 24012900
TI  - Distribution and accumulation of polybrominated diphenyl ethers (PBDEs) in Hong
      Kong mangrove sediments.
AB  - Polybrominated diphenyl ethers (PBDEs) have been used extensively as brominated
      flame retardants in various polymers, and have become serious environmental
      contaminants, particularly in coastal sediments. Mangrove wetlands are important
      coastal ecosystems in tropical and subtropical regions, and mangrove sediments
      are often the pollutant sinks due to their close proximity with human activities.
      In Hong Kong, sediment samples collected from five mangrove swamps were found to
      be contaminated with PBDEs and the eight measured BDE congeners, including BDE
      28, -47, -99, -100, -153, -154, -183 and -209 were detected in all mangrove
      sediments, indicating that these pollutants were widespread in Hong Kong mangrove
      wetlands. Among the five swamps, relatively high concentrations of PBDEs were
      recorded in Mai Po mangrove swamp in the northwestern Hong Kong, which is part of
      the RAMSAR site but is severely influenced by the pollution from the Pearl River
      Delta. The depth profile of PBDEs in sediment cores collected from Mai Po also
      showed the inputs of PBDEs in this mangrove swamp increased year by year. In all
      sediments, the concentrations of BDE-209 were 1-2 orders of magnitude higher than
      the other congeners in the same sediment. The concentrations of BDE-209 and
      ?PBDEs (defined as the sum of seven targeted BDE congeners except BDE-209) ranged
      from 1.53 to 75.9 ng g(-1) and from 0.57 to 14.4 ng g(-1), respectively. Among
      the targeted BDE congeners except BDE-209, slightly different composition was
      recorded among samples collected from different locations, with BDE-153 and -183
      being the pre-dominated congeners. In all mangrove swamps, except Tai O in the
      southwest of Hong Kong, ?PBDEs concentrations showed a common trend of
      landward>seaward>mudflat. The concentrations of ?PBDEs were significantly
      correlated with total organic matter (TOM) content in sediments but not with the
      sediment particle sizes in each mangrove swamp.

PMID- 24012901
TI  - Associations of phthalate concentrations in floor dust and multi-surface dust
      with the interior materials in Japanese dwellings.
AB  - Phthalates are widely used as plasticizers in numerous products. However, there
      has been some concern about the various effects they may have on human health.
      Thus, household phthalate levels are an important public health issue. While many
      studies have assessed phthalate levels in house dust, the association of these
      levels with building characteristics has scarcely been examined. The present
      study investigated phthalate levels in house dust samples collected from the
      living areas of homes, and examined associations between these phthalate levels
      and the interior materials. Dust was collected from two portions of the living
      area: floor dust from the entire floor surface, and multi-surface dust from
      objects more than 35 cm above the floor. The levels of seven phthalates were
      measured using gas chromatography/mass spectrometry in selective ion monitoring
      mode. Phthalate levels were higher in multi-surface dust than in floor dust.
      Among floor dust samples, those from dwellings with compressed wooden flooring
      had significantly higher levels of di-iso-butyl phthalate compared to those with
      other floor materials, while polyvinyl chloride (PVC) flooring was associated
      with higher di-2-ethylhexyl phthalate (DEHP) levels. Among multi-surface dust
      samples, higher levels of DEHP and di-iso-nonyl phthalate (DINP) were found in
      samples from homes with PVC wallpaper than without. The number of PVC interior
      materials was significantly positively correlated with the levels of DEHP and
      DINP in multi-surface dust. The phthalate levels in multi-surface dust were
      associated with the interior surface materials, and those in floor dust were
      directly related to the flooring materials. Our findings show that when using
      house dust as an exposure assessment, it is very important to note where the
      samples were collected from. The present report provides useful information about
      the association between phthalates and dust inside dwellings, which will assist
      with establishing public health provisions.

PMID- 24012902
TI  - Long term temporal and spatial changes in the distribution of polychlorinated
      biphenyls and polybrominated diphenyl ethers in Scottish soils.
AB  - Long term changes in polychlorinated biphenyl (PCB) and polybrominated diphenyl
      ether (PBDE) concentrations in soil from four transects across Scotland were
      measured in three surveys conducted between 1990 and 2007-9. Overall PCB level
      declined during this period (22.5 to 4.55 ng/g, p<0.001) but PBDEs increased
      (0.68 to 2.55 ng/g, p<0.001), reflecting the ban on PCB use in the 1980s while
      PBDE use increased until about 2004 when the use of penta-mix congener ceased in
      Europe. The proportion of lighter PCB congeners (28+52) present declined
      (p<0.001) primarily between 1990 and 1999. However, the proportion of lighter
      PBDE congeners (47+99) in the soil samples increased (p<0.01) from 1990 to 1999
      and declined (p<0.001) thereafter, probably reflecting the introduction of
      legislation banning penta-BDE products and the degradation of lighter congeners
      and their translocation. PCBs were slightly higher in two southernmost transects
      but PBDE concentrations were significantly higher (p<0.001) in the two southern
      transects than in the two northern transects. This may reflect proximity to areas
      of high population and industrial activity. It is concluded that temporal and
      spatial changes in the distribution of PCBs and PBDEs reflect geography, physical
      processes and legislation.

PMID- 24012903
TI  - Synthesis of cholesterol analogs having varying length alkyl side chains
      including cholesterol-23, 23, 24, 24, 25, 26, 26, 26, 27, 27, 27-d(11) as probes
      of cholesterol's functions and properties.
AB  - Cholesterol-23, 23, 24, 24, 25, 26, 26, 26, 27, 27, 27-d11 and nondeuterated long
      chain analogs of cholesterol were prepared by alkylation of cyano-containing
      sterols with isopentyl-d11 4-methylbenzenesulfonate (1.0equiv.) or with isoalkyl
      bromides, followed by reductive decyanation with excess potassium metal and a
      crown ether in toluene. The products are potentially useful probes of the role of
      the side-chain of cholesterol in the sterol's interactions with membrane lipids
      and proteins. 

PMID- 24012904
TI  - Histamine inhibits high mobility group box 1-induced adhesion molecule expression
      on human monocytes.
AB  - Cell-cell interaction through binding of adhesion molecules on monocytes to their
      ligands on T-cells plays roles in cytokine production and lymphocyte
      proliferation. High mobility group box 1 (HMGB1), an abundant and conserved
      nuclear protein, acts in the extracellular environment as a primary pro
      inflammatory signal. HMGB1 induces expression of intercellular adhesion molecule
      (ICAM), B7.1, B7.2 and CD40 on monocytes, resulting in production of interferon
      (IFN)-gamma and tumor necrosis factor (TNF)-alpha production and lymphocyte
      proliferation in human peripheral blood mononuclear cells (PBMCs). Histamine
      inhibits pro-inflammatory cytokine production via histamine H2-receptors;
      however, it is not known whether histamine inhibits HMGB1 activity. This study
      was designed to study the inhibitory effect of histamine on HMGB1 activity. We
      examined the effect of histamine on HMGB1-induced expression of ICAM-1, B7.1,
      B7.2 and CD40 on monocytes, production of IFN-gamma and TNF-alpha and lymphocyte
      proliferation in PBMCs. Histamine inhibited HMGB1 activity in a concentration
      dependent manner. The effects of histamine were partially ablated by the H2
      receptor antagonist, famotidine, and mimicked by the H2/H4-receptor agonists,
      dimaprit and 4-methylhistamine. Histamine induced cyclic adenosine monophosphate
      (cAMP) production in the presence and absence of HMGB1. The effects of histamine
      were reversed by the protein kinase A (PKA) inhibitor, H89, and mimicked by the
      membrane-permeable cAMP analog, dibutyryl cAMP (dbcAMP), and the adenylate
      cyclase activator, forskolin. These results together indicated that histamine
      inhibited HMGB1 activity. 

PMID- 24012905
TI  - Exposure of cardiomyocytes to angiotensin II induces over-activation of monoamine
      oxidase type A: implications in heart failure.
AB  - Several evidences indicate that increased cardiac mitochondrial monoamine oxidase
      type A (MAO-A) activity associates with a failing phenotype. Till now, the
      mechanism underlying such relation is largely unknown. We explored the hypothesis
      that exposure of cardiomyocytes to AT-II caused activation of MAO-A and also of
      catalase and aldehyde dehydrogenase activities, enzymes involved in degrading
      MAO's end products. Left ventricular cardiomyocytes were isolated from
      normoglycemic (N) and streptozotocin-injected (50 mg/kg) rats (D) treated or not
      treated with losartan (20 mg/kg/day in drinking water; DLos and NLos,
      respectively), a type 1 receptor (AT1) antagonist, for 3 weeks. In each group of
      cells, MAO, catalase and aldehyde dehydrogenase activities were measured
      radiochemically and spectrophotometrically. The same enzymes were also measured
      in HL-1 immortalized cardiomyocytes not exposed and exposed to AT-II (100 nM for
      18 h) in the absence and in the presence of irbesartan (1 MUM), an AT1
      antagonist. MAO-A catalase and aldehyde dehydrogenase activities were found
      significantly higher in D, than in N cells. MAO-A positively correlated with
      catalase activity in D cells. MAO-A and aldehyde dehydrogenase but not catalase
      over-activation, were prevented in DLos cells. Similarly, MAO-A activity, but not
      catalase and aldehyde dehydrogenase increased significantly in HL-1 cells acutely
      exposed to AT-II and this increase was prevented when irbesartan, an AT1
      antagonist was present. Over-activation of cardiomyocyte MAO-A activity is among
      acute (18 h) and short-term (2-weeks of diabetes) cardiac effects of AT-II and a
      novel target of AT1 antagonists, first line treatments of diabetic
      cardiomyopathy.

PMID- 24012906
TI  - Single stimulus learning in zebrafish larvae.
AB  - Learning about a moving visual stimulus was examined in zebrafish larvae using an
      automated imaging system and a t1-t2 design. In three experiments, zebrafish
      larvae were exposed to one of two inputs at t1 (either a gray bouncing disk or an
      identical but stationary disk) followed by a common test at t2 (the gray bouncing
      disk). Using 7days post-fertilization (dpf) larvae and 12 stimulus exposures,
      Experiment 1 established that these different treatments produced differential
      responding to the moving disk during testing. Larvae familiar with the moving
      test stimulus were significantly less likely to be still in its presence than
      larvae that had been exposed to the identical but stationary stimulus. Experiment
      2 confirmed this result in 7dpf larvae and extended the finding to 5 and 6dpf
      larvae. Experiment 3 found differential responding to the moving test stimulus
      with 4 or 8 stimulus exposures but not with just one exposure in 7dpf larvae.
      These results provide evidence for learning in very young zebrafish larvae. The
      merits and challenges of the t1-t2 framework to study learning are discussed. 

PMID- 24012907
TI  - Review of recent studies and issues regarding the P300-based complex trial
      protocol for detection of concealed information.
AB  - In this review, the evolution of new P300-based protocols for detection of
      concealed information is summarized. The P300-based complex trial protocol (CTP)
      is described as one such countermeasure (CM)-resistant protocol. Recent lapses in
      diagnostic accuracy (from 90% to 75%) with CTPs applied to mock crime protocols
      are summarized, as well as recent enhancements to the CTP which have restored
      accuracy. These enhancements include 1) use of performance feedback during
      testing, 2) use of other ERP components such as N200 in diagnosis, 3) use of
      auxiliary tests, including the autobiographical implicit association test, as
      leading to restored diagnostic accuracy, and 4) a study of the mechanisms
      underlying CMs. A novel, doubly efficient version of the CTP involving
      presentation of two probes in one trial is described as a new way to improve
      accuracy to levels above 90% in mock crime situations. Finally, a thorough
      analysis of the legal issues surrounding use of the CTP in U.S. is given. 

PMID- 24012908
TI  - Brain-computer interfaces for EEG neurofeedback: peculiarities and solutions.
AB  - Neurofeedback training procedures designed to alter a person's brain activity
      have been in use for nearly four decades now and represent one of the earliest
      applications of brain-computer interfaces (BCI). The majority of studies using
      neurofeedback technology relies on recordings of the electroencephalogram (EEG)
      and applies neurofeedback in clinical contexts, exploring its potential as
      treatment for psychopathological syndromes. This clinical focus significantly
      affects the technology behind neurofeedback BCIs. For example, in contrast to
      other BCI applications, neurofeedback BCIs usually rely on EEG-derived features
      with only a minimum of additional processing steps being employed. Here, we
      highlight the peculiarities of EEG-based neurofeedback BCIs and consider their
      relevance for software implementations. Having reviewed already existing packages
      for the implementation of BCIs, we introduce our own solution which specifically
      considers the relevance of multi-subject handling for experimental and clinical
      trials, for example by implementing ready-to-use solutions for pseudo-/sham
      neurofeedback. 

PMID- 24012909
TI  - Brief ED intervention may reduce teen dating violence.

PMID- 24012910
TI  - Assessing the physical-chemical properties and stability of dapivirine-loaded
      polymeric nanoparticles.
AB  - Nanocarriers may provide interesting delivery platforms for microbicide drugs and
      their characterization should be addressed early in development. Differently
      surface-engineered dapivirine-loaded, poly(epsilon-caprolactone) (PCL)-based
      nanoparticles (NPs) were obtained by nanoprecipitation using polyethylene oxide
      (PEO), sodium lauryl sulfate (SLS), or cetyltrimethylammonium bromide (CTAB) as
      surface modifiers. Physical-chemical properties of NP aqueous dispersions were
      evaluated upon storage at -20-40  degrees C for one year. NPs presented 170-200
      nm in diameter, roundish-shape, low polydispersity index (<=0.18), and high drug
      association efficiency (>=97%) and loading (>=12.7%). NPs differed in zeta
      potential, depending on surface modifier (PEO: -27.9 mV; SLS: -54.7 mV; CTAB:
      +42.4 mV). No interactions among formulation components were detected by
      differential scanning calorimetry (DSC) and Fourier transform infrared
      spectroscopy (FTIR), except for SLS-PCL NPs. Colloidal properties of NPs were
      lost at -20  degrees C storage. Negatively charged NPs were stable up to one year
      at 5-40 degrees C; as for CTAB-PCL NPs, particle aggregation was observed from 30
      to 90 days of storage depending on temperature. Colloidal instability affected
      the in vitro drug release of CTAB-PCL NPs after 360 days. In any case, no
      degradation of dapivirine was apparent. Overall, PEO-PCL and SLS-PCL NPs
      presented suitable properties as nanocarriers for dapivirine. Conversely, CTAB
      PCL NPs require additional strategies in order to increase stability.

PMID- 24012911
TI  - Precise quantification of transcription factors in a surface-based single
      molecule assay.
AB  - Biosensors have recognized a rapid development the last years in both industry
      and science. Recently, a single-molecule assay based on alternating laser
      excitation has been established for the quantitative detection of transcription
      factors. These proteins specifically recognize and bind DNA and play an important
      role in controlling gene expression. We implemented this assay format on a total
      internal reflection fluorescence microscope to detect transcription factors with
      immobilized single-molecule DNA biosensors. We quantify transcription factors via
      colocalization of the two halves of their binding site with immobilized single
      molecules of a two-color DNA biosensor. We could detect a model transcription
      factor, the bacterial lactose repressor, at different concentrations down to
      150pM. We found that robust modeling of stoichiometry derived TIRF data is
      achieved with Student's t-distributions and nonlinear least-squares estimation
      with weights equal to the inverse of the expected number of bin entries. This
      significantly improved transcription factor concentration estimates with respect
      to distribution modeling with Gaussians without adding notable computational
      effort. The proposed model may enhance the precision of other single-molecule
      assays quantifying molecular distributions. Our measurements reliably confirm
      that the immobilized biosensor format is more sensitive than a previously
      published solution based approach. 

PMID- 24012913
TI  - Diagnosing surgical site infection after cardiac surgery.

PMID- 24012912
TI  - Protonation of trimethylamine N-oxide (TMAO) is required for stabilization of RNA
      tertiary structure.
AB  - The osmolyte trimethylamine N-oxide (TMAO) stabilizes the tertiary but not the
      secondary structures of RNA. However, molecular dynamics simulations performed on
      the PreQ1 riboswitch showed that TMAO destabilizes the tertiary riboswitch
      structure, leading us to hypothesize that the presence of RNA could result in
      enhanced population of the protonated form, TMAOP. Constant pH replica exchange
      simulations showed that a percentage of TMAO is indeed protonated, thus
      contributing to the stability of the tertiary but not the secondary structure of
      PreQ1. TMAOP results in an unfavorable dehydration of phosphodiester backbone,
      which is compensated by electrostatic attraction between TMAOP and the phosphate
      groups. In addition, TMAOP interacts with specific sites in the tertiary RNA
      structure, mimicking the behavior of positively charged ions and of the PreQ1
      ligand in stabilizing RNA. Finally, we predict that TMAO-induced stabilization of
      RNA tertiary structures should be strongly pH dependent. 

PMID- 24012914
TI  - Value of sTREM-1, procalcitonin and CRP as laboratory parameters for postmortem
      diagnosis of sepsis.
AB  - OBJECTIVES: Triggering receptor expressed on myeloid cells-1 (TREM-1) was
      reported to be up-regulated in various inflammatory diseases as well as in
      bacterial sepsis. Increased cell-surface TREM-1 expression was also shown to
      result in marked plasma elevation of the soluble form of this molecule (sTREM-1)
      in patients with bacterial infections. In this study, we investigated sTREM-1,
      procalcitonin and C-reactive protein in postmortem serum in a series of sepsis
      related fatalities and control individuals who underwent medico-legal
      investigations. sTREM-1 was also measured in pericardial fluid and urine.
      METHODS: Two study groups were prospectively formed, a sepsis-related fatalities
      group and a control group. The sepsis-related fatalities group consisted of
      sixteen forensic autopsy cases. Eight of these had a documented clinical
      diagnosis of sepsis in vivo. The control group consisted of sixteen forensic
      autopsy cases with various causes of death. RESULTS: Postmortem serum sTREM-1
      concentrations were higher in the sepsis group with a mean value of 173.6 pg/ml
      in septic cases and 79.2 pg/ml in control individuals. The cutoff value of 90
      pg/ml provided the best sensitivity and specificity. Pericardial fluid sTREM-1
      values were higher in the septic group, with a mean value of 296.7 pg/ml in
      septic cases and 100.9 pg/ml in control individuals. The cutoff value of 135
      pg/ml provided the best sensitivity and specificity. Mean urine sTREM-1
      concentration was 102.9 pg/ml in septic cases and 89.3 pg/ml in control
      individuals. CONCLUSIONS: Postmortem serum sTREM-1, individually considered, did
      not provide better sensitivity and specificity than procalcitonin in detecting
      sepsis. However, simultaneous assessment of procalcitonin and sTREM-1 in
      postmortem serum can be of help in clarifying contradictory postmortem findings.
      sTREM-1 determination in pericardial fluid can be an alternative to postmortem
      serum in those situations in which biochemical analyses are required and blood
      collected during autopsy proves insufficient.

PMID- 24012916
TI  - Characterization of four nr5a genes and gene expression profiling for testicular
      steroidogenesis-related genes and their regulatory factors in response to
      bisphenol A in rare minnow Gobiocypris rarus.
AB  - Bisphenol A (BPA) widely used in the manufacture of numerous products is
      ubiquitous in aquatic environment. To explore the mechanisms of BPA-mediated
      actions, male rare minnow Gobiocypris rarus were exposed to BPA at concentrations
      of 5, 15, and 50 MUg/L for 14 and 35 days in the present study. Four subtypes of
      nr5a gene encoding important transcription factors for steroidogenesis were
      characterized, and tissue distribution analysis demonstrated distinct expression
      profiling of the four genes in G. rarus. BPA at environmentally relevant
      concentration (5 MUg/L) caused increase of gonadosomatic index (GSI) of male
      fish. In response to BPA, no obvious changes on the testis development were
      observed. Modulation of vtg mRNA expression by BPA suggests estrogenic and/or
      anti-estrogenic effects of BPA were dependent on exposed duration (14 or 35
      days). Gene expression profiling for testicular steroidogenesis-related genes,
      sexual steroid receptors, gonadotropin receptors, and transcription factors
      indicates differential regulation was dependent on exposure duration and dose of
      BPA. The correlation analysis at mRNA level demonstrates that the BPA-mediated
      actions on testicular steroidogenesis might involve sex steroid hormone receptor
      signaling, gonadotropin/gonadotropin receptor pathway, and transcription factors
      such as nuclear receptor subfamily 5, group A (Nr5a), fork head box protein L2
      (Foxl2).

PMID- 24012915
TI  - The Midwest Exercise Trial for the Prevention of Weight Regain: MET POWeR.
AB  - Weight reduction in overweight and obese individuals results in physiological and
      behavioral changes that make the prevention of weight regain more difficult than
      either initial weight loss or the prevention of weight gain. Exercise is
      recommended for the prevention of weight regain by both governmental agencies and
      professional organizations. To date, the effectiveness of exercise
      recommendations for the prevention of weight regain has not been evaluated in a
      properly designed, adequately powered trial. Therefore, we will conduct a
      randomized trial to evaluate the effectiveness of 3 levels of exercise on the
      prevention of weight regain, in initially overweight and obese sedentary men and
      women. Participants will complete a 3 month weight loss intervention of decreased
      energy intake (EI) and increased exercise (100 min/week). Participants achieving
      clinically significant weight loss (>= 5% of initial weight), will then be
      randomly assigned to 12 months of verified exercise at 3 levels (150, 225 or 300
      min/week). This study will evaluate: 1) the effectiveness of 3 levels of exercise
      on the prevention of weight regain over 12 months subsequent to clinically
      significant weight loss (>= 5%); 2) gender differences in weight regain in
      response to 3 levels of exercise; and 3) potential compensatory changes in daily
      physical activity (PA) and EI on weight regain in response to the 3 levels of
      exercise. The results of this investigation will provide information to develop
      evidence-based recommendations for the level of exercise associated with the
      prevention of weight regain.

PMID- 24012917
TI  - A comparison of random forest regression and multiple linear regression for
      prediction in neuroscience.
AB  - BACKGROUND: Regression is a common statistical tool for prediction in
      neuroscience. However, linear regression is by far the most common form of
      regression used, with regression trees receiving comparatively little attention.
      NEW METHOD: In this study, the results of conventional multiple linear regression
      (MLR) were compared with those of random forest regression (RFR), in the
      prediction of the concentrations of 9 neurochemicals in the vestibular nucleus
      complex and cerebellum that are part of the l-arginine biochemical pathway
      (agmatine, putrescine, spermidine, spermine, l-arginine, l-ornithine, l
      citrulline, glutamate and gamma-aminobutyric acid (GABA)). RESULTS: The R(2)
      values for the MLRs were higher than the proportion of variance explained values
      for the RFRs: 6/9 of them were >= 0.70 compared to 4/9 for RFRs. Even the
      variables that had the lowest R(2) values for the MLRs, e.g. ornithine (0.50) and
      glutamate (0.61), had much lower proportion of variance explained values for the
      RFRs (0.27 and 0.49, respectively). The RSE values for the MLRs were lower than
      those for the RFRs in all but two cases. COMPARISON WITH EXISTING METHODS: In
      general, MLRs seemed to be superior to the RFRs in terms of predictive value and
      error. CONCLUSION: In the case of this data set, MLR appeared to be superior to
      RFR in terms of its explanatory value and error. This result suggests that MLR
      may have advantages over RFR for prediction in neuroscience with this kind of
      data set, but that RFR can still have good predictive value in some cases.

PMID- 24012918
TI  - Contribution of muscarinic M1 receptors to the cholinergic suppression of
      synaptic responses in layer II of the entorhinal cortex.
AB  - The entorhinal cortex is thought to play roles in sensory and mnemonic function,
      and the cholinergic suppression of the strength of synaptic inputs is likely to
      have important impacts on these processes. Field excitatory postsynaptic
      potentials (fEPSPs) in the medial entorhinal cortex evoked by stimulation of the
      piriform cortex are suppressed during theta EEG activity in behaving animals, and
      cholinergic receptor activation suppresses synaptic responses both in vivo, and
      in layer II entorhinal neurons in vitro. Here, we have used in vitro field
      potential recordings to investigate the transmitter receptors that mediate the
      cholinergic suppression of synaptic responses in layer I inputs to layer II of
      the medial entorhinal cortex. Bath-application of the cholinergic agonist
      carbachol suppressed the amplitude of fEPSPs with an EC50 of 5.3MUM, and enhanced
      paired-pulse ratio. The M2/M4 preferring receptor blocker methoctramine, or the
      M4 receptor blocker PD102807, did not prevent the cholinergic suppression.
      However, the M1/M4 receptor blocker pirenzepine and the M1 receptor blocker
      VU0255035 reduced the suppression, suggesting that the cholinergic suppression of
      synaptic responses in the entorhinal cortex is dependent in large part on
      activation of M1 receptors. 

PMID- 24012919
TI  - Angiotensin-(1-7) prevents radiation-induced inflammation in rat primary
      astrocytes through regulation of MAP kinase signaling.
AB  - About 500,000 new cancer patients will develop brain metastases in 2013. The
      primary treatment modality for these patients is partial or whole brain
      irradiation which leads to a progressive, irreversible cognitive impairment.
      Although the exact mechanisms behind this radiation-induced brain injury are
      unknown, neuroinflammation in glial populations is hypothesized to play a role.
      Blockers of the renin-angiotensin system (RAS) prevent radiation-induced
      cognitive impairment and modulate radiation-induced neuroinflammation. Recent
      studies suggest that RAS blockers may reduce inflammation by increasing
      endogenous concentrations of the anti-inflammatory heptapeptide angiotensin-(1-7)
      [Ang-(1-7)]. Ang-(1-7) binds to the AT(1-7) receptor and inhibits MAP kinase
      activity to prevent inflammation. This study describes the inflammatory response
      to radiation in astrocytes characterized by radiation-induced increases in (i) IL
      1beta and IL-6 gene expression; (ii) COX-2 and GFAP immunoreactivity; (iii)
      activation of AP-1 and NF-kappaB transcription factors; and (iv) PKCalpha, MEK,
      and ERK (MAP kinase) activation. Treatment with U-0126, a MEK inhibitor,
      demonstrates that this radiation-induced inflammation in astrocytes is mediated
      through the MAP kinase pathway. Ang-(1-7) inhibits radiation-induced
      inflammation, increases in PKCalpha, and MAP kinase pathway activation
      (phosphorylation of MEK and ERK). Additionally Ang-(1-7) treatment leads to an
      increase in dual specificity phosphatase 1 (DUSP1). Furthermore, treatment with
      sodium vanadate (Na3VO4), a phosphatase inhibitor, blocks Ang-(1-7) inhibition of
      radiation-induced inflammation and MAP kinase activation, suggesting that Ang-(1
      7) alters phosphatase activity to inhibit radiation-induced inflammation. These
      data suggest that RAS blockers inhibit radiation-induced inflammation and prevent
      radiation-induced cognitive impairment not only by reducing Ang II but also by
      increasing Ang-(1-7) levels. 

PMID- 24012920
TI  - Disparities in use of laparoscopic hysterectomies: a nationwide analysis.
AB  - STUDY OBJECTIVE: To determine patient and hospital characteristics that were
      associated with undergoing laparoscopic hysterectomy compared with abdominal
      hysterectomy. DESIGN: Canadian Task Force Classification II-3. METHODS: In this
      retrospective cohort study, we analyzed the 2010 Healthcare Cost and Utilization
      Project Nationwide Inpatient Sample database. All women who underwent
      laparoscopic or abdominal hysterectomy for either menorrhagia or leiomyoma were
      included based on International Classification of Diseases, Ninth Revision
      coding. A linear model with binomial distribution and logit link function was
      used to determine patient and hospital characteristics associated with
      hysterectomy approach. MAIN RESULTS: A total of 32 436 patients were included in
      this study. Of these, 32% patients underwent laparoscopic hysterectomies, and 67%
      underwent abdominal hysterectomies. With regard to patient characteristics, women
      younger than 35 years old were more likely to undergo laparoscopic hysterectomy
      when compared with each of the other age categories (p < .001). White women were
      more likely to undergo laparoscopic hysterectomy than black women, Hispanic
      women, or women classified as "other" races (p < .001 for all comparisons). With
      regard to median income, patients from the lowest national quartile were less
      likely to undergo laparoscopic hysterectomy when compared with each of the other
      3 national quartiles for income (p = .01, p < .001, p = .001, respectively).
      Payment by private insurance was associated with laparoscopic hysterectomy when
      compared with payment by Medicare or payment by insurance category "other" (p <
      .001 for both). With regard to hospital characteristics, hospitals in the
      Northeast were more likely to have laparoscopic hysterectomies than hospitals in
      the Midwest or South (p < .001 for both comparisons); urban hospitals were more
      likely than rural hospitals (p < .001); teaching hospitals were more likely than
      nonteaching hospitals (p < .001); and government-owned hospitals were less likely
      than private, nonprofit or private, investor owned (p < .001 for both
      comparisons). CONCLUSIONS: Despite the increased popularity of and training in
      laparoscopic hysterectomies, there remains an obvious disparity in its delivery
      with regard to patient and hospital characteristics. Further investigation is
      needed on the etiology of this disparity and interventions that may alleviate it.

PMID- 24012921
TI  - Laparoscopic hysterectomy in case of uteri weighing >=1 kilogram: a series of 71
      cases and review of the literature.
AB  - STUDY OBJECTIVE: To present our experience with laparoscopic hysterectomy (LH)
      for uteri weighing 1 kilogram or more and to provide a systematic review of the
      available English literature. DESIGN: Retrospective analysis and review of the
      literature (Canadian Task Force Classification II-2). SETTING: Department of
      Obstetrics and Gynecology, University of Insubria, Varese, Italy. PATIENTS: All
      women in whom LH was attempted at the Department of Obstetrics and Gynecology,
      University of Insubria for uteri weighing >=1 kg were included in the present
      study. Demographic characteristics and perioperative details of patients were
      prospectively recorded in our institutional surgical database. We also performed
      a systematic review of the English literature to identify studies including at
      least 1 case of LH for uteri weighing >=1 kg. INTERVENTIONS: Hysterectomy for
      uteri >=1 kg was performed through a total laparoscopic approach with vaginal
      morcellation of the uterus in the majority of patients and transvaginal closure
      of the vaginal vault in all cases. MEASUREMENTS AND MAIN RESULTS: LH was
      attempted in a total of 71 women. The median uterine weight was 1120 g (1000-2860
      g). Three (4.2%) conversions to open surgery were needed. The median operative
      time and blood loss were 120 minutes (55-360 minutes) and 200 mL (10-1000 mL),
      respectively. No intraoperative and 2 (2.8%) postoperative complications
      occurred. Our review identified 6 studies reporting details of LH for uteri
      weighing >=1 kg for a total of 62 patients; conversion to open surgery was
      necessary in 6 (9.7%) patients, and an additional 13 (21%) received a
      minilaparotomic incision to extract the uterus. The overall complication rate
      reported in the literature was 11.4%. CONCLUSION: LH represents a possibility
      even in cases of uteri weighing >=1 kg. In a dedicated setting with high
      endoscopic experience, conversion and complication rates appear acceptable.

PMID- 24012922
TI  - The value of diagnostic hysteroscopy before operative hysteroscopy for suspected
      abnormal intrauterine findings.
AB  - STUDY OBJECTIVE: To evaluate the accuracy of diagnostic office hysteroscopy in
      the detection of abnormal uterine findings in symptomatic and asymptomatic
      patients and compare it with the accuracy of operative hysteroscopy. DESIGN: A
      retrospective analysis of all women after operative hysteroscopy between 2010 and
      2012 in our institution (Canadian Task Force classification II-2). SETTING: The
      department of gynecology in a tertiary referral medical center. PATIENTS: One
      hundred thirty-two patients with a mean age of 48 years after diagnostic office
      hysteroscopy and subsequent operative hysteroscopy. INTERVENTIONS: Operative
      hysteroscopy. MEASUREMENTS AND MAIN RESULTS: We collected demographic and
      clinical data from patients' charts. The indications as well as findings of the
      previous diagnostic modality (transvaginal ultrasound [TVUS] and diagnostic
      hysteroscopy) were gathered and compared with the final tissue diagnosis obtained
      via operative hysteroscopy. Positive predictive values in diagnostic hysteroscopy
      were calculated for common pathological intrauterine findings. Forty-eight
      patients (37%) were menopausal, and 84 (63%) were premenopausal. The indications
      for hysteroscopy were abnormal uterine bleeding in 46% of patients and suspected
      uterine finding in 44%. A TVUS preceded the diagnostic hysteroscopy in 105 women
      (80%). Older female age, menopausal status, and abnormal intrauterine findings
      larger than 15 mm were associated with significantly greater true-positive rates
      on diagnostic hysteroscopy (i.e., the suspected findings on diagnostic
      hysteroscopy were verified by final pathology). Uterine bleeding during the
      interval between procedures was marginally significant and associated with
      greater false-positive results. Bleeding as opposed to routine evaluation of
      uterine cavity, interval between procedures, location of intrauterine finding,
      and hormone replacement therapy were not associated with greater true-positive
      values. CONCLUSION: Although diagnostic hysteroscopy is superior to TVUS in the
      assessment of polyps, it contributes little to TVUS when myomas and endometrial
      hyperplasia are suspected. Therefore, it should not be used routinely as an
      interface between TVUS and operative hysteroscopy when such findings such are
      suspected. Furthermore, in premenopausal patients with abnormal uterine bleeding
      between diagnostic and operative procedures and when small (<15 mm) polyps are
      suspected, it might be worthwhile to repeat a diagnostic procedure before
      operative hysteroscopy.

PMID- 24012923
TI  - Impact of obesity on outcomes of hysterectomy.
AB  - STUDY OBJECTIVES: To evaluate the impact of obesity on complications of
      hysterectomy. STUDY DESIGN: Retrospective cohort study (Canadian Task Force II
      2). SETTING: The Department of Obstetrics and Gynecology, Women and Infants
      Hospital of Rhode Island, Providence, RI. PATIENTS: Patients who had a
      hysterectomy at WIH between July 2006 and January 2009. INTERVENTIONS:
      Hysterectomy by any mode. MEASUREMENTS AND MAIN RESULTS: We collected data from
      medical records of all laparoscopic hysterectomies during the time period and
      collected data from a random subset of abdominal and vaginal hysterectomies. The
      independent variable, body mass index, was grouped according to World Health
      Organization guidelines. A composite of surgical complications was generated.
      Multivariable logistic regression was used to estimate adjusted odds ratios (ORs)
      and 95% confidence intervals (CIs). We collected data from 907 hysterectomies,
      and 29.9% (n = 267) of the population was obese. Eighteen percent of patients (n
      = 154) had at least 1 complication. Compared to non-obese women, obese women were
      at increased odds of having any complication (OR 1.62, 95% CI 1.12-2-34).
      Performing subgroup analyses by mode of hysterectomy and controlling for
      confounding factors, we were unable to detect differences odds of complications
      between obese and non-obese women who underwent either an abdominal, vaginal, or
      laparoscopic hysterectomy. CONCLUSION: In our study, we found that among women
      who had a hysterectomy, obese women had a higher rate of complications than
      nonobese women.

PMID- 24012924
TI  - Vulvar mass in a patient with type 1 neurofibromatosis.

PMID- 24012925
TI  - Charisma: an integrated approach to automatic H&E-stained skeletal muscle cell
      segmentation using supervised learning and novel robust clump splitting.
AB  - Histological image analysis plays a key role in understanding the effects of
      disease and treatment responses at the cellular level. However, evaluating
      histology images by hand is time-consuming and subjective. While semi-automatic
      and automatic approaches for image segmentation give acceptable results in some
      branches of histological image analysis, until now this has not been the case
      when applied to skeletal muscle histology images. We introduce Charisma, a new
      top-down cell segmentation framework for histology images which combines image
      processing techniques, a supervised trained classifier and a novel robust clump
      splitting algorithm. We evaluate our framework on real-world data from intensive
      care unit patients. Considering both segmentation and cell property
      distributions, the results obtained by our method correspond well to the ground
      truth, outperforming other examined methods. 

PMID- 24012926
TI  - Antidepressant effects after short-term and chronic stimulation of the subgenual
      cingulate gyrus in treatment-resistant depression.
AB  - BACKGROUND: Deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG)
      is an experimental approach in treatment-resistant depression (TRD). Apart from
      its potential long-term antidepressant effects acute stimulation effects have
      been described. We investigated putative neuroanatomical clusters in which such
      acute effects accumulate and followed patients over the long-term. METHODS: We
      assessed safety and efficacy of DBS in six patients with TRD receiving bilateral
      DBS with electrodes implanted in the SCG. First, high intensity 130 Hz
      stimulation was applied on five consecutive days after surgery for 24 h
      comprising a sham condition in a double-blind, randomized design. Acute
      stimulation was conducted at all four homologous electrode contacts on both
      sides. Afterwards, chronic stimulation was initiated and the clinical effect was
      evaluated at 24-36 weeks compared to baseline (50% reduction in HAMD scores). The
      primary outcome criterion was depression severity as assessed with the Hamilton
      Depression Rating Scale (HAMD-24); secondary outcome parameters were the
      Montgomery-Asberg Rating-Scale and Beck Depression Inventory following DBS. The
      clinical effect over the three scores was compared to sham stimulation and was
      correlated to the anatomical localization of active contacts by stereotactically
      delimiting the cluster of most effective contacts in responding patients.
      RESULTS: Acute 24 h of stimulation showed only moderate reductions in mean HAMD
      24, MADRS and BDI scores. At the last observation (24-36 weeks), two patients
      were remitters (HAMD-24 < 10) and the four other patients were non-responders.
      CONCLUSIONS: Our results confirm that stimulation of the SCG is capable of
      exerting moderate acute and chronic antidepressant effects. The predictive value
      of these findings needs to be addressed in future studies.

PMID- 24012927
TI  - Menadione (Vitamin K3) decreases melanin synthesis through ERK activation in Mel
      Ab cells.
AB  - Menadione is a synthetic vitamin K3 derivative. Here, we examined the effects of
      menadione on melanogenesis and its related signaling pathways. Our results showed
      that melanin content was significantly reduced after menadione treatment in a
      dose-dependent manner. However, menadione treatment did not reduce tyrosinase
      activity directly. Wnt signaling is known to play a major role in the control of
      melanin synthesis. Thus, we tested the effects of menadione treatment on GSK3beta
      and beta-catenin signaling, but found that menadione did not influence either of
      these signaling pathways. We also investigated changes in the phosphorylation of
      ERK, which is related to melanin regulation. These results indicated that
      menadione treatment led to the phosphorylation of ERK. Additionally, menadione
      treatment reduced both MITF and tyrosinase protein levels. Treatment with
      PD98059, a specific ERK pathway inhibitor, restored menadione-induced melanin
      reduction and also prevented MITF and tyrosinase downregulation by menadione.
      These results suggest that the hypopigmentary action of menadione is due to MITF
      and tyrosinase downregulation by ERK activation. 

PMID- 24012928
TI  - Levosimendan inhibits interleukin-1beta-induced cell migration and MMP-9
      secretion in rat cardiac fibroblasts.
AB  - Cell migration and matrix metalloproteinases (MMPs) secretion in cardiac
      fibroblasts are important processes in the cardiac remodeling during the
      development of cardiac diseases and are regulated by proinflammatory cytokines.
      Although levosimendan, a novel inotropic agent, is expected to have some
      beneficial influences on preventing cardiac remodeling, its effects on
      proinflammatory cytokines-induced functional changes in cardiac fibroblasts have
      not been clarified. Therefore, we investigated the effects of levosimendan on
      interleukin (IL)-1beta-induced MMP-9 secretion and migration in adult rat cardiac
      fibroblasts. Primary cardiac fibroblasts were isolated from adult male Wistar
      rats. MMP-9 secretion in culture medium and extracellular signal-regulated kinase
      (ERK) phosphorylation in cell lysate were measured by using Western blotting.
      Gelatin zymography was performed to measure activity of secreted MMP-9. MMP-9
      mRNA expression in the cell was measured by using reverse transcription
      polymerase chain reaction. Boyden chamber assay was performed for detection of
      migration. Levosimendan (3-100 MUM) concentration-dependently inhibited IL-1beta
      (4 ng/ml)-induced MMP-9 secretion, activity and mRNA expression. Levosimendan
      inhibited IL-1beta (4 ng/ml)-induced ERK phosphorylation. Levosimendan (10 and
      100 MUM) inhibited IL-1beta-induced migration, and CTTHWGFTLC peptide (10 MUM),
      an MMP inhibitor, or PD98059 (50 MUM), an ERK inhibitor, also suppressed it. The
      present study for the first time demonstrated in adult rat cardiac fibroblasts
      that levosimendan inhibits IL-1beta-induced migration at least partly through the
      inhibition of MMP-9 secretion via suppressing ERK phosphorylation.

PMID- 24012929
TI  - Bee venom phospholipase A2-induced phasic contractions in mouse rectum:
      independent roles of eicosanoid and gap junction proteins and their loss in
      experimental colitis.
AB  - Various events including digestion and inflammation are regulated by secreted
      phospholipase A2 (sPLA2) in gastrointestinal tissues, however, the role of sPLA2
      on contractile activity has not been elucidated. We investigated the effect of
      bee venom PLA2 (bvPLA2), which is homologous to the central domain of group III
      sPLA2, on contractile activity in mouse rectum. The longitudinal preparations of
      rectum showed rhythmic phasic contractions (RPCs) with varied amplitude and high
      frequency. Treatment with bvPLA2 at 1 MUg/ml increased amplitudes of RPCs without
      marked changes in frequency and basal tone. RPCs by bvPLA2 were affected neither
      by atropine nor by inhibition of nitric oxide synthase, and partly inhibited by
      dual inhibition of the cyclooxygenase and lipoxygenase pathways. Pretreatment of
      bvPLA2 with dithiothreitol, which inhibits the enzyme activity, partly reduced
      bvPLA2-induced RPCs, and arachidonic acid-increased RPCs were completely
      abolished by cyclooxygenase/lipoxygenase inhibition. Phasic contractions have
      been shown to be regulated by gap junction and to be decreased in
      gastrointestinal tissues with experimental colitis. Treatment with inhibitors of
      gap junction proteins, 50 MUM 18beta-glycyrrhetinic acid and 100 MUM
      carbenoxolone, partly and almost completely reduced bvPLA2-induced RPCs without
      and with the cyclooxygenase/lipoxygenase inhibitors, respectively, but not
      arachidonic acid-induced RPCs. In rectum from mouse having colitis, where total
      levels and modified forms of connexin43 increased, bvPLA2-induced RPCs were
      markedly decreased. Our results suggest that both arachidonic acid metabolism and
      gap junction proteins independently regulated the sPLA2-induced RPCs in mouse
      rectum. An increased expression and/or modification of connexin43 may influence
      sPLA2-induced RPCs in rectum with colitis.

PMID- 24012930
TI  - Dual effect of capsaicin on cell death in human osteosarcoma G292 cells.
AB  - Thirty percent of osteosarcoma patients die within 5 years. New agents that
      induce apoptosis of osteosarcoma cells might be therapeutically useful. Here, we
      characterized the apoptotic mechanism induced by capsaicin in G292 osteosarcoma
      cells. Our results show that capsaicin induces an increase in the cytosolic
      Ca(2+) concentration which is independent of the extracellular Ca(2+)
      concentration and depletes intracellular Ca(2+) stores, suggesting the presence
      of endoplasmic reticulum transient receptor potential vanilloid receptor type 1.
      Capsaicin also activates the mitochondrial caspase 3-dependent death cascade.
      Rapamycin, an inhibitor of mammalian target of rapamycin, evokes autophagy, as do
      capsaicin or thapsigargin, a sarco(endo)plasmic reticulum Ca(2+) ATPase inhibitor
      that causes Ca(2+) store depletion. Capsaicin-induced cell death is completely
      inhibited by co-treatment with the pan-caspase inhibitor Z-VAD-fmk and increased
      by the autophagy inhibitor 3-methyladenine, suggesting the existence of an
      autophagy-dependent anti-apoptotic mechanism. Capsaicin also induces ERK
      phosphorylation, which acts as a downstream effector of autophagy. 3
      Methyladenine or PD98059, an ERK kinase inhibitor, restores capsaicin-induced
      cell death in the presence of Z-VAD-fmk, suggesting that inhibition of autophagy
      activates a second cell death pathway that is caspase-independent. Taken
      together, our data show that capsaicin causes Ca(2+) depletion of intracellular
      Ca(2+) stores and simultaneously activates the mitochondrial caspase-dependent
      death cascade and autophagy-dependent ERK activation and that the latter
      counteracts a second death signaling pathway that is caspase-independent. 

PMID- 24012931
TI  - The potential interaction of MARCKS-related peptide and diltiazem on acrolein
      induced airway mucus hypersecretion in rats.
AB  - Airway mucus hypersecretion is recognized as a pathophysiological feature of
      airway inflammation. Ca2+ entry and myristoylated alanine-rich C kinase substrate
      translocation are considered as important factors in such process. To investigate
      the potential interaction of myristoylated alanine-rich C kinase substrate
      (MARCKS)-related peptide and diltiazem on acrolein-induced airway mucus
      hypersecretion in rats, rat model of airway mucus hypersecretion was established
      by inhalation of acrolein on 12 consecutive days. MARCKS-related peptide,
      diltiazem, saline or the combination (MARCKS-related peptide+diltiazem) was
      intratracheally administered respectively. The rats were received pilocarpine to
      stimulate mucus release before sacrifices. The expression of Mucin5ac in
      bronchoalveolar lavage fluid (BALF) was measured by ELISA. Intracellular Muc5ac
      level was detected by immunohistochemical staining and western-blot. Muc5ac mRNA
      in lung was analyzed by RT-PCR. RESULTS: Instillation of MARCKS-related peptide
      attenuated the release of Muc5ac in BALF induced by acrolein(p<0.05). Diltiazem
      alone had no effect on mucus hypersecretion induced by acrolein. However, the
      release of Muc5ac in BALF was further reduced when challenged with simultaneous
      instillation with MARCKS-related peptide and diltiazem, compared with MARCKS
      related peptide alone (p<0.05). The intracellular level of Muc5ac in lung was
      increased when treated with MARCKS-related peptide alone or MARCKS-related
      peptide plus diltiazem (p<0.05). Nevertheless, diltiazem alone did not take
      effect as above. CONCLUSIONS: In the model of airway mucus hypersecretion induced
      by acrolein, MARCKS-related peptide attenuated mucus secretion and the inhibitory
      effect was enhanced by diltiazem, which may be due to a further diminution of the
      intracellular free calcium concentration and retention of mucin within epithelial
      goblet cells.

PMID- 24012932
TI  - Quantitative EDXS analysis of organic materials using the zeta-factor method.
AB  - In this study we successfully applied the zeta-factor method to perform
      quantitative X-ray analysis of organic thin films consisting of light elements.
      With its ability to intrinsically correct for X-ray absorption, this method
      significantly improved the quality of the quantification as well as the accuracy
      of the results compared to conventional techniques in particular regarding the
      quantification of light elements. We describe in detail the process of
      determining sensitivity factors (zeta-factors) using a single standard specimen
      and the involved parameter optimization for the estimation of zeta-factors for
      elements not contained in the standard. The zeta-factor method was then applied
      to perform quantitative analysis of organic semiconducting materials frequently
      used in organic electronics. Finally, the results were verified and discussed
      concerning validity and accuracy. 

PMID- 24012933
TI  - Enhanced light element imaging in atomic resolution scanning transmission
      electron microscopy.
AB  - We show that an imaging mode based on taking the difference between signals
      recorded from the bright field (forward scattering region) in atomic resolution
      scanning transmission electron microscopy provides an enhancement of the
      detectability of light elements over existing techniques. In some instances this
      is an enhancement of the visibility of the light element columns relative to
      heavy element columns. In all cases explored it is an enhancement in the signal
      to-noise ratio of the image at the light column site. The image formation
      mechanisms are explained and the technique is compared with earlier approaches.
      Experimental data, supported by simulation, are presented for imaging the oxygen
      columns in LaAlO3. Case studies looking at imaging hydrogen columns in YH2 and
      lithium columns in Al3Li are also explored through simulation, particularly with
      respect to the dependence on defocus, probe-forming aperture angle and detector
      collection aperture angles.

PMID- 24012934
TI  - Dynamic scattering theory for dark-field electron holography of 3D strain fields.
AB  - Dark-field electron holography maps strain in crystal lattices into reconstructed
      phases over large fields of view. Here we investigate the details of the lattice
      strain-reconstructed phase relationship by applying dynamic scattering theory
      both analytically and numerically. We develop efficient analytic linear
      projection rules for 3D strain fields, facilitating a straight-forward
      calculation of reconstructed phases from 3D strained materials. They are used in
      the following to quantify the influence of various experimental parameters like
      strain magnitude, specimen thickness, excitation error and surface relaxation. 

PMID- 24012935
TI  - Lattice and strain analysis of atomic resolution Z-contrast images based on
      template matching.
AB  - A real space approach is developed based on template matching for quantitative
      lattice analysis using atomic resolution Z-contrast images. The method, called
      TeMA, uses the template of an atomic column, or a group of atomic columns, to
      transform the image into a lattice of correlation peaks. This is helped by using
      a local intensity adjusted correlation and by the design of templates. Lattice
      analysis is performed on the correlation peaks. A reference lattice is used to
      correct for scan noise and scan distortions in the recorded images. Using these
      methods, we demonstrate that a precision of few picometers is achievable in
      lattice measurement using aberration corrected Z-contrast images. For
      application, we apply the methods to strain analysis of a molecular beam epitaxy
      (MBE) grown LaMnO3 and SrMnO3 superlattice. The results show alternating
      epitaxial strain inside the superlattice and its variations across interfaces at
      the spatial resolution of a single perovskite unit cell. Our methods are general,
      model free and provide high spatial resolution for lattice analysis.

PMID- 24012936
TI  - When to use the projection assumption and the weak-phase object approximation in
      phase contrast cryo-EM.
AB  - The projection assumption (PA) and the weak-phase object approximation (WPOA) are
      commonly used to model image formation in cryo-electron microscopy. For
      simulating the next step in resolution improvement we show that it is important
      to revisit these two approximations as well as their limitations. Here we start
      off by inspecting both approximations separately to derive their respective
      conditions of applicability. The thick-phase grating approximation (TPGA) imposes
      less strict conditions on the interaction potential than PA or WPOA and gives
      comparable exit waves as a multislice calculation. We suggest the ranges of
      applicability for four models (PA, PA+WPOA, WPOA, and TPGA) given different
      interaction potentials using exit wave simulations. The conditions of
      applicability for the models are based on two measures, a worst-case (safest) and
      an average criterion. This allows us to present a practical guideline for when to
      use each image formation model depending on the spatial frequency, thickness and
      strength of the interaction potential of a macromolecular complex. 

PMID- 24012937
TI  - Continuous capacitance-voltage spectroscopy mapping for scanning microwave
      microscopy.
AB  - A new method, scanning sawtooth capacitance spectroscopy (SSCS), is proposed to
      measure a map of capacitance/voltage curves (C-V) by applying a low frequency
      voltage sawtooth signal (20-100 Hz) to the AFM tip while scanning. For this a
      scanning microwave microscope (SMM) is used to acquire calibrated capacitance
      data in the high frequency range of 1-20 GHz. While the capacitance is acquired
      pixel by pixel, the applied voltage signal is recorded as well, and each pixel of
      the capacitance is assigned the corresponding voltage value. Assuming the voltage
      variable is smooth over time, adjacent pixels within a scan line will have
      similar voltage values and a small sequence of neighboring pixels can be combined
      into a virtual C-V spectroscopy curve. With standard SMM operation parameters
      roughly 26,000 C-V curves can be acquired within few minutes data acquisition
      time. The method is demonstrated for n-type and p-type silicon semiconductor
      samples and can be applied to other samples including new materials and bio
      membranes.

PMID- 24012938
TI  - Effective temperature of an ultracold electron source based on near-threshold
      photoionization.
AB  - We present a detailed description of measurements of the effective temperature of
      a pulsed electron source, based on near-threshold photoionization of laser-cooled
      atoms. The temperature is determined by electron beam waist scans, source size
      measurements with ion beams, and analysis with an accurate beam line model.
      Experimental data is presented for the source temperature as a function of the
      wavelength of the photoionization laser, for both nanosecond and femtosecond
      ionization pulses. For the nanosecond laser, temperatures as low as 14 +/- 3 K
      were found; for femtosecond photoionization, 30 +/- 5 K is possible. With a
      typical source size of 25 MUm, this results in electron bunches with a relative
      transverse coherence length in the 10-4 range and an emittance of a few nm rad.

PMID- 24012939
TI  - Is magnetic chiral dichroism feasible with electron vortices?
AB  - We discuss the feasibility of detecting magnetic transitions with focused
      electron vortex probes, suggested by selection rules for the magnetic quantum
      number. We theoretically estimate the dichroic signal strength in the L2,3 edge
      of ferromagnetic d metals. It is shown that under realistic conditions, the
      dichroic signal is undetectable for nanoparticles larger than ~1 nm. This is
      confirmed by a key experiment with nanometer-sized vortices.

PMID- 24012940
TI  - A new constrained ICA approach for optimal signal decomposition in polarized
      light imaging.
AB  - BACKGROUND: Polarized light imaging (PLI) has evolved into a powerful
      neuroimaging tool to analyze fiber tracts with submillimeter resolution in
      microtome sections of postmortem human brain tissue. In PLI polarized light
      changes its polarization state while passing through birefringent tissue, i.e.,
      myelinated axons, which results in sinusoidal signals that characterize different
      fiber orientations. Noise, light scatter and filter inhomogeneities of the
      polarimeter interfere with the original sinusoidal PLI signals, which have direct
      effects on the accuracy of subsequent fiber modeling. New method: In our recent
      publications we have shown that the sinusoidal signal at each pixel location in
      PLI images can be restored utilizing independent component analysis (ICA). We now
      have further improved the signal separation quality by introducing a new
      constrained ICA algorithm (cICAP) where the component selection is directly
      included. In cICAP an analytical expression of the expected signal of interest is
      implemented as a priori information. RESULTS: The algorithm precisely decomposes
      the deteriorated PLI signals into its underlying source signals. As such, the
      approach enhances sinusoidal basis functions and is therefore optimal for the
      extraction of independent spatial maps from PLI images. Comparison with existing
      methods: The new algorithm performs better and is faster compared to other well
      known ICA algorithms. CONCLUSION: The decomposition in cICAP is optimal with
      respect to separation and identification of the sinusoidal nature of the PLI
      signal. In this way the identification of the relevant components is
      automatically included and does not require any further component selection tool.

PMID- 24012941
TI  - The ART-strategy: sequential assessment of the ART score predicts outcome of
      patients with hepatocellular carcinoma re-treated with TACE.
AB  - BACKGROUND & AIMS: Recently, we developed the ART score (assessment for re
      treatment with TACE) to guide the decision for a second transarterial
      chemoembolization (TACE-2) in patients with hepatocellular carcinoma (HCC).
      Patients with an ART score of 0-1.5 points gained benefit from a second TACE
      session, while patients with an ART score >=2.5 points did not. Here, we
      investigated (1) the prognostic significance of the ART score prior to the third
      (TACE-3) and fourth TACE (TACE-4), and (2) the feasibility of an ART score guided
      re-treatment strategy by sequential assessment of the ART score in HCC patients
      treated with multiple TACE sessions. METHODS: 109 patients, diagnosed with
      intermediate stage HCC and treated with >=3 TACE sessions between January 1999
      and December 2009 at the Medical Universities of Vienna and Innsbruck, were
      included. The ART score prior to each TACE session was assessed in comparison to
      the TACE naive liver. The prognostic performance of the ART score before TACE-3
      and 4 was evaluated with and without stratification based on the ART score prior
      to the respective last intervention. RESULTS: The pre-TACE-3 ART score
      discriminated two groups with different prognosis and remained a valid predictor
      of OS independent of Child-Pugh score (5-7 points), CRP-levels and tumor
      characteristics. Even in patients with an initially beneficial ART score (0-1.5
      points) before TACE-2, repeated ART score assessment before TACE-3 identified a
      subgroup of patients with dismal prognosis (median OS: 27.8 vs. 10.8 months,
      p<0.001). Similar results were observed when the ART score was applied before
      TACE-4. CONCLUSIONS: The sequential assessment of the ART score identifies
      patients with dismal prognosis prior to each TACE session.

PMID- 24012942
TI  - The bed nucleus of the stria terminalis has developmental and adult forms in
      mice, with the male bias in the developmental form being dependent on testicular
      AMH.
AB  - Canonically, the sexual dimorphism in the brain develops perinatally, with adult
      sexuality emerging due to the activating effects of pubescent sexual hormones.
      This concept does not readily explain why children have a gender identity and
      exhibit sex-stereotypic behaviours. These phenomena could be explained if some
      aspects of the sexual brain networks have childhood forms, which are transformed
      at puberty to generate adult sexuality. The bed nucleus of stria terminalis
      (BNST) is a dimorphic nucleus that is sex-reversed in transsexuals but not
      homosexuals. We report here that the principal nucleus of the BNST (BNSTp) of
      mice has developmental and adult forms that are differentially regulated. In 20
      day-old prepubescent mice, the male bias in the principal nucleus of the BNST
      (BNSTp) was moderate (360 +/- 6 vs 288 +/- 12 calbindin(+ve) neurons, p <
      0.0001), and absent in mice that lacked a gonadal hormone, AMH. After 20 days,
      the number of BNSTp neurons increased in the male mice by 25% (p < 0.0001) and
      decreased in female mice by 15% (p = 0.0012), independent of AMH. Adult male AMH
      deficient mice had a normal preference for sniffing female pheromones (soiled
      bedding), but exhibited a relative disinterest in both male and female
      pheromones. This suggests that male mice require AMH to undergo normal social
      development. The reported observations provide a rationale for examining AMH
      levels in children with gender identity disorders and disorders of socialization
      that involve a male bias.

PMID- 24012943
TI  - Systemic and intra-rhinal-cortical 17-beta estradiol administration modulate
      object-recognition memory in ovariectomized female rats.
AB  - Previous studies using the novel-object-preference (NOP) test suggest that
      estrogen (E) replacement in ovariectomized rodents can lead to enhanced novelty
      preference. The present study aimed to determine: 1) whether the effect of E on
      NOP performance is the result of enhanced preference for novelty, per se, or
      facilitated object-recognition memory, and 2) whether E affects NOP performance
      through actions it has within the perirhinal cortex/entorhinal cortex region
      (PRh/EC). Ovariectomized rats received either systemic chronic low 17-beta
      estradiol (E2; ~20 pg/ml serum) replacement alone or in combination with systemic
      acute high administration of estradiol benzoate (EB; 10 MUg), or in combination
      with intracranial infusions of E2 (244.8 pg/MUl) or vehicle into the PRh/EC. For
      one of the intracranial experiments, E2 was infused either immediately before,
      immediately after, or 2 h following the familiarization (i.e., learning) phase of
      the NOP test. In light of recent evidence that raises questions about the
      internal validity of the NOP test as a method of indexing object-recognition
      memory, we also tested rats on a delayed nonmatch-to-sample (DNMS) task of object
      recognition following systemic and intra-PRh/EC infusions of E2. Both systemic
      acute and intra-PRh/EC infusions of E enhanced novelty preference, but only when
      administered either before or immediately following familiarization. In contrast,
      high E (both systemic acute and intra-PRh/EC) impaired performance on the DNMS
      task. The findings suggest that while E2 in the PRh/EC can enhance novelty
      preference, this effect is probably not due to an improvement in object
      recognition abilities.

PMID- 24012944
TI  - Early manipulation of juvenile hormone has sexually dimorphic effects on mature
      adult behavior in Drosophila melanogaster.
AB  - Hormones are critical for the development, maturation, and maintenance of
      physiological systems; therefore, understanding their involvement during
      maturation of the brain is important for the elucidation of mechanisms by which
      adults become behaviorally competent. Changes in exogenous and endogenous factors
      encountered during sexual maturation can have long lasting effects in mature
      adults. In this study, we investigated the role of the gonadotropic hormone,
      juvenile hormone (JH), in the modulation of adult behaviors in Drosophila. Here
      we utilized methoprene (a synthetic JH analog) and precocene (a JH synthesis
      inhibitor) to manipulate levels of JH in sexually immature male and female
      Drosophila with or without decreased synthesis of neuronal dopamine (DA).
      Locomotion and courtship behavior were assayed once the animals had grown to
      sexual maturity. The results demonstrate a sexually dimorphic role for JH in the
      modulation of these centrally controlled behaviors in mature animals that is
      dependent on the age of the animals assayed, and present DA as a candidate
      neuronal factor that differentially interacts with JH depending on the sex of the
      animal. The data also suggest that JH modulates these behaviors through an
      indirect mechanism. Since gonadotropic hormones and DA interact in mammals to
      affect brain development and later function, our results suggest that this
      mechanism for the development of adult behavioral competence may be
      evolutionarily conserved. 

PMID- 24012946
TI  - Insights into fungal pathogenesis from the iatrogenic epidemic of Exserohilum
      rostratum fungal meningitis.
AB  - In 2012 the medical community in the United States faced an unprecedented
      outbreak of fungal meningitis caused by Exserohilum rostratum associated with
      injections of contaminated lots of methyprednilsone acetate. Rapid response by
      public health authorities led to the identification of the cause of the outbreak
      and the epidemic quickly abated, even though new cases were still being reported
      many months later. Although the cause of the outbreak is known there are many
      uncertainties regarding the management of infected individuals and the long term
      risk for those who were exposed to this organism. The epidemic of E. rostratum
      infections illustrates how an organism that normally has low pathogenic potential
      for humans can transform into a very dangerous pathogen when conditions are
      changed such that skin barriers are breached while it is simultaneously delivered
      with an immunosuppressive drug. Furthermore, this epidemic highlights the
      potential threats to human and animal health from the fungal kingdom. 

PMID- 24012945
TI  - Endogenous oxytocin is necessary for preferential Fos expression to male odors in
      the bed nucleus of the stria terminalis in female Syrian hamsters.
AB  - Successful reproduction in mammals depends on proceptive or solicitational
      behaviors that enhance the probability of encountering potential mates. In female
      Syrian hamsters, one such behavior is vaginal scent marking. Recent evidence
      suggests that the neuropeptide oxytocin (OT) may be critical for regulating this
      behavior. Blockade of OT receptors in the bed nucleus of the stria terminalis
      (BNST) or the medial preoptic area (MPOA) decreases vaginal marking responses to
      male odors; lesion data suggest that BNST, rather than MPOA, mediates this
      effect. However, how OT interacts with sexual odor processing to drive
      preferential solicitation is not known. To address this issue, intact female
      Syrian hamsters were exposed to male or female odors and their brains processed
      for immunohistochemistry for Fos, a marker of recent neuronal activation, and OT.
      Additional females were injected intracerebroventricularly (ICV) with an oxytocin
      receptor antagonist (OTA) or vehicle, and then tested for vaginal marking and Fos
      responses to sexual odors. Colocalization of OT and Fos in the paraventricular
      nucleus of the hypothalamus was unchanged following exposure to male odors, but
      decreased following exposure to female odors. Following injections of OTA, Fos
      expression to male odors was decreased in BNST, but not in MPOA or the medial
      amygdala (MA). Fos expression in BNST may be functionally relevant for vaginal
      marking, given that there was a positive correlation between Fos expression and
      vaginal marking for BNST, but not MPOA or MA. Together, these data suggest that
      OT facilitation of neuronal activity in BNST underlies the facilitative effects
      of OT on solicitational responses to male odors. 

PMID- 24012947
TI  - An allele-specific PCR system for rapid detection and discrimination of the
      CYP2C19*4A, *4B, and *17 alleles: implications for clopidogrel response testing.
AB  - CYP2C19 is involved in the metabolism of clinically relevant drugs, including the
      antiplatelet prodrug clopidogrel, which has prompted interest in clinical CYP2C19
      genotyping. The CYP2C19*4B allele is defined by both gain-of-function [c.-806C>T
      (*17)] and loss-of-function [c.1A>G (*4)] variants on the same haplotype;
      however, current genotyping and sequencing assays are unable to determine the
      phase of these variants. Thus, the aim of this study was to develop an assay that
      could rapidly detect and discriminate the related *4A, *4B, and *17 alleles. An
      allele-specific PCR assay, composed of four unique primer mixes that specifically
      interrogate the defining *17 and *4 variants, was developed by using samples (n =
      20) with known genotypes, including the *4A, *4B, and/or *17 alleles. The assay
      was validated by testing 135 blinded samples, and the results were correlated
      with CYP2C19 genotyping and allele-specific cloning/sequencing. Importantly,
      among the six *4 carriers in the validation cohort, after allele-specific PCR
      testing both samples with a *1/*4 genotype were reclassified to *1/*4A, all three
      samples with a *4/*17 genotype were reclassified to *1/*4B, and a sample with a
      *4/*17/*17 genotype was reclassified to *4B/*17. In conclusion, this rapid and
      robust allele-specific PCR assay can refine CYP2C19 genotyping and metabolizer
      phenotype classification by determining the phase of the defining *17 and *4
      variants, which may have utility when testing CYP2C19 for clopidogrel response. 

PMID- 24012948
TI  - Monitoring of influenza viruses in Western Siberia in 2008-2012.
AB  - Western Siberia is of great importance in ecology and epidemiology of influenza.
      This territory is nesting area for great amount of bird species. Territorial
      relations of Western Siberian birds that are established during seasonal
      migration are extremely wide since this region is an intersection point of bird
      migration flows wintering in different regions of the world: Europe, Africa,
      Middle East, Central Asia, Hindustan, and South East Asia. Reassortant influenza
      viruses that can cause outbreak among population may emerge in Western Siberia
      with high probability. Thus, it is extremely important to carry out widespread
      study of circulated viruses, their molecular biological properties, phylogenetic
      links in this region, as well as herd immunity to influenza virus serotypes with
      epidemic potential. 

PMID- 24012949
TI  - Retrospective molecular integrated epidemiology of Chagas disease in Colombia.
AB  - American trypanosomiasis is a very complex zoonosis that is present throughout
      South America, Central America, and Mexico and continues to represent a serious
      threat to the health of countries in the region. The parasite infects 150 species
      from 24 families of domestic and wild mammals and shows remarkable genetic
      variability evinced in at least seven discrete typing units (DTU's) named TcI
      TcVI with the presence of a novel genotype associated with bats named TcBat.
      These DTUs show a wide range of geographical and host distributions. Our study
      aimed to establish the relationship between the genetic diversity of Trypanosoma
      cruzi and the diverse clinical manifestations of infected patients and unravel
      the molecular eco-epidemiology in the epizootic and enzootic scenarios in
      Colombia. We undertook intensive sampling in 17 departments of Colombia among 11
      triatomine species, 9 mammalian reservoir species and humans and obtained 637
      biological clones that were subsequently analyzed using nuclear and mitochondrial
      molecular markers. TcI was the most prevalent (80.7%) followed by TcII (7.2%),
      TcIII (3.9%), TcIV (5%), TcV (0.8%), TcVI (1.6%) and TcBat (0.8%). Within
      domestic foci, TcI (70%) was the most prevalent, followed by TcII (20%), TcIII
      (1.6%), TcIV (3.6%), TcV (2.2%) and TcVI (2,6%); within sylvatic foci, TcI (85%)
      was the most prevalent, followed by TcII (0.3%), TcIII (5.5%), TcIV (7%), TcVI
      (1.1%) and TcBat (1.1%). The results suggest the occurrence of the seven DTUs and
      strict associations of independent DTUs with the host and environment in
      Colombia. The implications are discussed herein. 

PMID- 24012950
TI  - A panel of 16 full-length HCV genomes was characterized in China belonging to
      genotypes 1-6 including subtype 2f and two novel genotype 6 variants.
AB  - In this study, we characterized the full-length genomes of 16 HCV isolates
      obtained from patients in a single hospital in China using overlapping PCR
      followed by DNA sequencing. The obtained genomes are 9414-9628 nucleotides in
      length, and each genome contains a single ORF of 9021-9102 nucleotides. Nine
      genomes represent the common subtypes 1a, 1b, 2a, 2b, 3a, 3b, and 6a, while seven
      represent the infrequent lineages 1c, 2f, 4d, and 5a, and two novel genotype 6
      variants. GZ51969 and GZ52540 are subtype 1b isolates belonging to two unique
      clusters designated A and B, which account for 29.5% and 59.5% of the 1b
      infections in China, respectively. ZS542 and GZ98799 represent the first two
      complete genomes of the provisionally assigned subtype 2f. ZS96 and ZS202 are
      novel genotype 6 variants that may qualify for two new subtypes. ZS17, ZS537, and
      ZS631 represent three alien subtypes, namely, 1c, 4d, and 5a, which were detected
      in China for the first time in this study and may have been recently introduced
      as a result of globalization. Taken together, these results confirmed a large
      variety of HCV taxonomic lineages in China through the sequencing of their full
      length genomes. These lineages represent six genotypes, 11 subtypes, and two
      novel variants. They were characterized for achieving a better understanding of
      the HCV genetic variation patterns and for possible future research applications.

PMID- 24012951
TI  - Off-frequency listening in subjects with chronic tinnitus.
AB  - The occurrence of subjective tinnitus has been linked to cochlear damage, as most
      tinnitus patients have impaired hearing, and animal studies have shown that the
      induction of hearing loss can lead to behavioural signs of tinnitus. In tinnitus
      patients, the pure-tone audiogram is the main source of information about
      cochlear damage, but hearing thresholds alone may not adequately reflect its
      magnitude. Etchelecou et al. (2011) reported that the majority of patients with
      acute tinnitus post impulse noise exposure showed off-frequency listening (OFL),
      which is not readily observed in pure-tone audiograms. We investigated the
      possibility of OFL occurring in subjects with chronic tinnitus by testing twenty
      subjects who had experienced tinnitus for more than a year. OFL was assessed by
      measuring psychophysical tuning curves using a forward-masking paradigm. OFL
      occurred in 13 out of 20 subjects, 12 of whom also did not perceive frequencies
      above 8 kHz. Such unresponsive frequencies (UFs) were also present in three
      subjects without OFL. The tinnitus spectrum generally reached its highest values
      at the edge of or within the frequency regions with OFL or UFs, but there was no
      significant correlation between edge frequencies and the frequency with the
      highest tinnitus pitch similarity rating. When OFL and UFs were taken as evidence
      for cochlear dead regions, 16/20 subjects passed the criterion for cochlear dead
      regions. The remaining four subjects showed neither OFL nor UFs.

PMID- 24012952
TI  - A comparison of the clinical and experimental characteristics of four acute
      surgical pain models: dental extraction, bunionectomy, joint replacement, and
      soft tissue surgery.
AB  - When a clinical trial of an analgesic produces a negative finding, it is
      important to consider the influence (if any) of experimental error on the
      validity of that result. Although efforts to identify and minimize experimental
      error in chronic pain investigations have begun in earnest, less work has been
      performed on the optimization of acute pain methodology. Of the acute surgical
      pain methodology articles that have been published over the last decade, almost
      all focus on either the dental or bunion model. Analgesics are typically
      evaluated in a variety of surgical models that eventually include hospital-based
      models (eg, joint replacement and soft tissue surgery). Every surgical procedure
      has unique clinical characteristics that must be considered to optimize study
      design and conduct. Much of the methodological knowledge garnered from bunion and
      dental studies is applicable to other surgical models, but some extrapolations
      are hazardous. The purposes of this review were (1) to qualitatively describe the
      clinical and experimental characteristics of the 4 classic surgical models:
      dental extraction, bunionectomy, joint replacement, and soft tissue surgery; and
      (2) to quantitatively compare the models by analyzing 3 factors: effect size,
      enrollment rate, and demographics. We found that the dental extraction and
      bunionectomy models had higher assay sensitivity than the joint replacement and
      soft tissue surgery models. It is probable that this finding is secondary to the
      superior experimental conditions under which the dental and bunion models are
      executed (utilization of few centers that have the ability to reduce surgical,
      anesthetic, and postoperative confounders). 

PMID- 24012953
TI  - Pain and the onset of depressive and anxiety disorders.
AB  - Patients with pain may be at increased risk of developing a first episode of
      depressive or anxiety disorder. Insight into possible associations between
      specific pain characteristics and such a development could help clinicians to
      improve prevention and treatment strategies. The objectives of this study were to
      examine the impact of pain symptomatology on depression and anxiety onset and to
      determine whether these associations are independent of subthreshold depressive
      and anxiety symptoms. Data from the Netherlands Study of Depression and Anxiety,
      collected between 2004 and 2011, were used. A total of 614 participants with no
      previous history and no current depression or anxiety at baseline were followed
      up for 4 years. Onset of depressive or anxiety disorder was assessed at 2- and 4
      year follow-up by Composite International Diagnostic Interview. Baseline pain
      characteristics were location, duration, and severity, as assessed by chronic
      pain grade. Onset of depressive or anxiety disorder occurred in 15.5% of
      participants. Using Cox survival analyses, onset of depression and anxiety was
      associated with 6 pain locations (neck, back, head, orofacial area, abdomen, and
      joints; hazard ratio [HR]=1.96 to 4.02; P<.05), increasing number of pain
      locations (HR=1.29; P<.001), and higher severity of pain (HR=1.57; P<.001). By
      contrast, there was no association with duration of pain symptoms (HR=1.47;
      P=.12). Independent of subthreshold affective symptoms, only joint pain and
      increasing number of pain locations were still significantly associated with
      depression and anxiety onset. Clinicians should be aware that regardless of
      affective symptoms, pain, particularly at multiple locations, is a risk indicator
      for developing depressive and anxiety disorders.

PMID- 24012954
TI  - Proteomic-based identification of Apg-2 as a therapeutic target for chronic
      myeloid leukemia.
AB  - The oncogenic BCR/ABL tyrosine kinase induces constitutive enhanced "spontaneous"
      DNA damage and unfaithful repair in Philadelphia chromosome positive leukemia
      cells. Here, we investigated the changes of protein profile in H2O2-induced DNA
      damage/repair in BaF3-MIGR1 and BaF3-BCR/ABL cells through a proteomic strategy
      consisting of two-dimensional gel electrophoresis (2-DE) coupled with MALDI-TOF
      mass spectrometry. In total, 41 spots were differentially expressed and 13
      proteins were identified with further MS analysis. Two essential proteins, Proto
      oncogene tyrosine-protein kinase ABL1 (c-ABL) and Heat shock 70kDa protein 4 (Apg
      2), were confirmed by Western blot and showed consistent changes with proteomic
      results. Moreover, functional analysis demonstrated that inhibition of Apg-2 not
      only decreased cell proliferation, but also induced cell apoptosis in BCR/ABL
      positive cells (BaF3-BCR/ABL, BaF3-BCR/ABL(T315I)). We also proved that Apg-2
      inhibition aggravated H2O2 induced damage in BCR/ABL positive cells, and enhanced
      the sensitivity of BaF3-BCR/ABL(T315I) to STI571. Taken together, the findings in
      this work provide us with some clues to a better understanding of the molecular
      mechanisms underlying BCR/ABL in the DNA damage/repair processes and demonstrated
      that Apg-2 would be a valid target for anti-leukemia drug development. 

PMID- 24012955
TI  - ERK and RSK regulate distinct steps of a cellular program that induces transition
      from multicellular epithelium to single cell phenotype.
AB  - The ERK (extracellular signal-regulated kinases) cascade has an evolutionarily
      conserved three tier architecture consisting of protein kinases Raf, MEK
      (MAPK/ERK kinase) and ERK. Following activation, ERK phosphorylates various
      cellular elements leading to diverse cellular responses. Downstream of ERK the
      family of p90 ribosomal S6 kinases (RSKs) has been proven to be an important
      conveyor of ERK signaling, however, little is known if ERK and RSK coordinate
      their functions to generate a specific biological response. Here we show that in
      epithelial cells conditional activation of the ERK pathway causes phenotypic
      conversion of epithelial cells to autonomously migrating cells. This process
      involves two sequential steps characterized by loss of apical-basal polarity
      followed by cell scattering. The activation of ERK, but not RSK, is sufficient
      for the execution of the first step and it requires calpain mediated remodeling
      of actin cytoskeleton. Conversely, RSK regulates the successive stage
      characterized by cell-cell contact weakening and increased cellular migration.
      Thus, ERK and RSK regulate different cellular subprograms and coordinated
      execution of these subprograms in time generates a relevant biological response.
      Our data also suggest that the mechanism by which the ERK pathway controls a
      cellular response may be distributed between ERK and RSK, rather than being
      elicited by a single effector kinase. 

PMID- 24012958
TI  - Single nucleotide polymorphisms of ADRB2 gene and their association with
      susceptibility for Plasmodium falciparum malaria and asthma in an Indian
      population.
AB  - The essential route to blood parasitaemia in malaria, erythrocyte invasion is
      facilitated by activation of the G-protein coupled receptor signaling pathway
      mediated by the beta2-adrenoreceptor as one of the proteins on the surface of red
      blood cells. The effectiveness of bronchodilators and inhaled corticosteroids in
      the clinical treatment for asthma patients also depend on polymorphisms in the
      beta2-adrenoreceptor gene (ADRB2). In a case control study, individuals affected
      by Plasmodium falciparum malaria, asthma and controls were tested for association
      of six ADRB2 single nucleotide polymorphisms (SNPs) viz. rs1042711, rs1801704,
      rs1042713, rs1042714, rs1042717 and rs1042718, by direct DNA sequencing. The
      rs1801704 locus was significantly associated with malaria when compared against
      controls. The rs1042713 polymorphism was associated with forced expiratory flow
      between 25% and 75% of the FVC in asthma patients, pre (p=0.048) and post
      (p=0.038) treatment measurements. Predicted haplotype of the six SNPs computed
      from genotype data showed T-T-A-C-G-C conferred significant risk of malaria
      (p=0.02) whereas T-T-A-C-G-A was associated with risk of asthma (p=0.02). The
      haplotype T-T-G-C-G-C was protective against both malaria (p=0.02) as well as
      asthma (p=0.026) and C-C-G-G-G-C was protective uniquely for asthma (p=0.04). A
      significant outcome was that all variant alleles at the SNP loci were part of the
      haplotype conferring resistance to malaria disease and asthma, except rs1042713
      and rs1042718 which showed very high frequency in asthma. The pairwise linkage
      disequilibrium (LD) estimates showed a distinct LD block of all SNP loci (D'=1 or
      >0.8) in malaria patients. This characteristic haplotype block was disrupted in
      the controls due to non-significant pairwise LD of the SNP loci; and a more
      extensive disruption of the block was noted in asthma patients. The study
      provides evidence for the proposed role of beta2-adrenoreceptor mediated
      molecular mechanisms in etiology of malaria, as well as asthma disease and drug
      response, for further clinical and therapeutic application studies. 

PMID- 24012957
TI  - Identification of circulating porcine-human reassortant G4P[6] rotavirus from
      children with acute diarrhea in China by whole genome analyses.
AB  - P[6] group A rotavirus (RVA) strains identified in four stool specimens collected
      from children with acute diarrhea in Guangxi Province, southern China in 2010,
      with unknown G type were further analyzed by full genomic analysis. It was
      revealed by whole genome sequencing that 11 genomic cognate gene segments of
      these P[6] RVA strains shared almost 100% nucleotide identities and all exhibited
      an identical G4-P[6]-I1-R1-C1-M1-A8-N1-T1-E1-H1 genotype constellation.
      Phylogenetic analyses of VP7, VP1-VP4, NSP1, NSP2, NSP4 and NSP5 genes revealed
      that these Guangxi G4P[6] RVA strains were closely related to porcine and porcine
      like human RVAs, while VP6 and NSP3 were closely related to those of common human
      RVAs. Interestingly, the four infants from whom these specimens were collected
      had come from different villages and/or towns. They had not contacted with each
      other and had had acute diarrhea before admitted into the same hospital. The
      genomic analyses and the clinical data revealed that these four Guangxi G4P[6]
      RVA strains from China were reassortants possessing VP6 and NSP3 gene segments of
      human origin yet all other nine gene segments of porcine origin. It is the first
      report on porcine-human reassortant G4P[6] RVA with identical genome
      configuration circulating in children. 

PMID- 24012959
TI  - Breast cancer-derived K172N, D301V mutations abolish Na+/H+ exchanger regulatory
      factor 1 inhibition of platelet-derived growth factor receptor signaling.
AB  - Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) is a scaffold protein known to
      interact with a number of cancer-related proteins. nherf1 Mutations (K172N and
      D301V) were recently identified in breast cancer cells. To investigate the
      functional properties of NHERF1, wild-type and cancer-derived nherf1 mutations
      were stably expressed in SKMES-1 cells respectively. NHERF1-wt overexpression
      suppressed the cellular malignant phenotypes, including proliferation, migration,
      and invasion. nherf1 Mutations (K172N and D301V) caused complete or partial loss
      of NHERF1 functions by affecting the PTEN/NHERF1/PDGFRbeta complex formation,
      inactivating NHERF1 inhibition of PDGF-induced AKT and ERK activation, and
      attenuating the tumor-suppressor effects of NHERF1-wt. These results further
      demonstrated the functional consequences of breast cancer-derived nherf1
      mutations (K172N and D301V), and suggested the causal role of NHERF1 in tumor
      development and progression.

PMID- 24012956
TI  - Rapid degeneration of rod photoreceptors expressing self-association-deficient
      arrestin-1 mutant.
AB  - Arrestin-1 binds light-activated phosphorhodopsin and ensures timely signal
      shutoff. We show that high transgenic expression of an arrestin-1 mutant with
      enhanced rhodopsin binding and impaired oligomerization causes apoptotic rod
      death in mice. Dark rearing does not prevent mutant-induced cell death, ruling
      out the role of arrestin complexes with light-activated rhodopsin. Similar
      expression of WT arrestin-1 that robustly oligomerizes, which leads to only
      modest increase in the monomer concentration, does not affect rod survival.
      Moreover, WT arrestin-1 co-expressed with the mutant delays retinal degeneration.
      Thus, arrestin-1 mutant directly affects cell survival via binding partner(s)
      other than light-activated rhodopsin. Due to impaired self-association of the
      mutant its high expression dramatically increases the concentration of the
      monomer. The data suggest that monomeric arrestin-1 is cytotoxic and WT arrestin
      1 protects rods by forming mixed oligomers with the mutant and/or competing with
      it for the binding to non-receptor partners. Thus, arrestin-1 self-association
      likely serves to keep low concentration of the toxic monomer. The reduction of
      the concentration of harmful monomer is an earlier unappreciated biological
      function of protein oligomerization. 

PMID- 24012960
TI  - Knockdown of dual specificity phosphatase 4 enhances the chemosensitivity of MCF
      7 and MCF-7/ADR breast cancer cells to doxorubicin.
AB  - BACKGROUND: Breast cancer is the major cause of cancer-related deaths in females
      world-wide. Doxorubicin-based therapy has limited efficacy in breast cancer due
      to drug resistance, which has been shown to be associated with the epithelial-to
      mesenchymal transition (EMT). However, the molecular mechanisms linking the EMT
      and drug resistance in breast cancer cells remain unclear. Dual specificity
      phosphatase 4 (DUSP4), a member of the dual specificity phosphatase family, is
      associated with cellular proliferation and differentiation; however, its role in
      breast cancer progression is controversial. METHODS: We used cell viability
      assays, Western blotting and immunofluorescent staining, combined with siRNA
      interference, to evaluate chemoresistance and the EMT in MCF-7 and adriamycin
      resistant MCF-7/ADR breast cancer cells, and investigate the underlying
      mechanisms. RESULTS: Knockdown of DUSP4 significantly increased the
      chemosensitivity of MCF-7 and MCF-7/ADR breast cancer cells to doxorubicin, and
      MCF-7/ADR cells which expressed high levels of DUSP4 had a mesenchymal phenotype.
      Furthermore, knockdown of DUSP4 reversed the EMT in MCF-7/ADR cells, as
      demonstrated by upregulation of epithelial biomarkers and downregulation of
      mesenchymal biomarkers, and also increased the chemosensitivity of MCF-7/ADR
      cells to doxorubicin. CONCLUSIONS: DUSP4 might represent a potential drug target
      for inhibiting drug resistance and regulating the process of the EMT during the
      treatment of breast cancer.

PMID- 24012961
TI  - Multilayer films of layered double hydroxide/polyaniline and their ammonia
      sensing behavior.
AB  - This paper reports the fabrication of layered double hydroxide (LDH)/conductive
      polymer multilayer films by alternate assembly of exfoliated ZnAl-LDH nanosheets
      and polyaniline (PANI) on silicon wafer substrates using the layer-by-layer (LBL)
      deposition technology. UV-vis absorption spectroscopy indicates a stepwise and
      regular growth of the (LDH/PANI)n multilayer films upon increasing deposition
      cycles. Scanning electron microscopy (SEM) and atomic force microscopy (AFM)
      demonstrate that the surfaces of the films are microscopy smooth and uniform with
      a thickness of 2 nm per bilayer. Furthermore, the resulting (LDH/PANI)n
      multilayer films possess high selectively response to ammonia at room
      temperature. The presence of LDH nanosheets plays a critical role on the gas
      sensing for the pure PANI film has very low response to ammonia. The LBL assembly
      process based on LDH combines the conducting polymer and nano-inorganic material,
      which provides opportunities to develop new inorganic-organic films for gas
      sensing.

PMID- 24012962
TI  - Structural ceramics containing electric arc furnace dust.
AB  - In the present work the stabilization of electric arc furnace dust EAFD waste in
      structural clay ceramics was investigated. EAFD was collected over eleven
      production days. The collected waste was characterized for its chemical
      composition by Flame Atomic Absorption Spectroscopy. By powder XRD the crystal
      structure was studied while the fineness of the material was determined by a
      laser particle size analyzer. The environmental characterization was carried out
      by testing the dust according to EN12457 standard. Zn, Pb and Cd were leaching
      from the sample in significant amounts. The objective of this study is to
      investigate the stabilization properties of EAFD/clay ceramic structures and the
      potential of EAFD utilization into structural ceramics production (blocks).
      Mixtures of clay with 2.5% and 5% EAFD content were studied by TG/DTA, XRD, SEM,
      EN12457 standard leaching and mechanical properties as a function of firing
      temperature at 850, 900 and 950  degrees C. All laboratory facilities maintained
      20 +/- 1  degrees C. Consequently, a pilot-scale experiment was conducted with an
      addition of 2.5% and 5% EAFD to the extrusion mixture for the production of
      blocks. During blocks manufacturing, the firing step reached 950  degrees C in a
      tunnel kiln. Laboratory heating/cooling gradients were similar to pilot scale
      production firing. The as produced blocks were then subjected to quality control
      tests, i.e. dimensions according to EN772-17, water absorbance according to EN772
      6, and compressive strength according to EN772-1 standard, in laboratory
      facilities certified under EN17025. The data obtained showed that the
      incorporation of EAFD resulted in an increase of mechanical strength. Moreover,
      leaching tests performed according to the Europeans standards on the EAFD-block
      samples showed that the quantities of heavy metals leached from crushed blocks
      were within the regulatory limits. Thus the EAFD-blocks can be regarded as
      material of no environmental concern.

PMID- 24012963
TI  - Elucidating the role of phenolic compounds in the effectiveness of DOM adsorption
      on novel tailored activated carbon.
AB  - Two novel tailored activated carbons (BC-41-OG and BC-41-MnN) with favorable
      physicochemical characteristics were successfully prepared for adsorption of
      dissolved natural organic matter (DOM) by applying systematically chemical and
      thermal treatment. This research was conducted to investigate the impact of the
      presence of phenolics on the adsorption capacity of DOM. Isotherm tests were
      performed for both humic acid (HA) and phenolics on both novel tailored activated
      carbons and commercial activated carbon F400. The presence of phenolics display a
      significant effect on hindering the adsorption of HA, however; the
      physicochemical characteristics of novel activated carbons (surface metal oxides
      and mesoporosity) can play an important role in alleviating this effect. In
      contrast, F400, with a relatively lower mesoporosity and surface basicity as
      compared to the developed adsorbents, was severely impacted by the
      oligomerization of phenolic compounds. The adsorption capacity of DOM in presence
      of phenolics was further studied in a continuous flow microcolumn system. The
      column results showed that both BC-41-OG and BC-41-MnN have not only higher HA
      adsorption capacity but also better selective adsorption ability than F400. 

PMID- 24012964
TI  - Regulation of TREM-1 expression by 1,25-dihydroxyvitamin D3 in human
      monocytes/macrophages.
AB  - Triggering receptor expressed on myeloid cells-1 (TREM-1) is a recently
      identified cell surface receptor that is expressed mainly on monocytes and
      neutrophils, and acts as an amplifier of immune responses. In this study,
      1,25(OH)2D3 strongly upregulated the expression of TREM-1 in human monocytes and
      macrophages. 1,25(OH)2D3 stimulated TREM-1 mRNA expression by augmenting
      transcription, and not by inhibiting mRNA degradation. The upregulated expression
      of TREM-1 by 1,25(OH)2D3 was dependent on the NF-kappaB signaling pathway and
      required new protein synthesis in differentiated U937 macrophages. Our results
      show that 1,25(OH)2D3 can affect the innate and inflammatory responses by
      upregulating TREM-1 expression, and suggest that 1,25(OH)2D3 may function as an
      enhancer of the innate immune response by upregulating TREM-1 expression, in
      addition to inducing the antimicrobial peptide cathelicidin. 

PMID- 24012965
TI  - Relationships among grocery nutrition label users and consumers' attitudes and
      behavior toward restaurant menu labeling.
AB  - In the United States (US), based on the 2010 Affordable Care Act, restaurant
      chains and similar retail food establishments with 20 or more locations are
      required to begin implementing calorie information on their menus. As enacting of
      the law begins, it is important to understand its potential for improving
      consumers' healthful behaviors. Therefore, the objective of this study was to
      explore relationships among users of grocery nutrition labels and attitudes
      toward restaurant menu labeling, along with the caloric content of their
      restaurant menu selection. Study participants were surveyed and then provided
      identical mock restaurant menus with or without calories. Results found that
      participants who used grocery nutrition labels and believed they would make
      healthy menu selections with nutrition labels on restaurant menus made healthier
      menu selections, regardless of whether the menu displayed calories or not.
      Consumers' nutrition knowledge and behaviors gained from using grocery nutrition
      labels and consumers' desire for restaurants to provide nutrition menu labels
      have a positive effect on their choosing healthful restaurant menu items. 

PMID- 24012966
TI  - Scutellarin and caffeic acid ester fraction, active components of Dengzhanxixin
      injection, upregulate neurotrophins synthesis and release in
      hypoxia/reoxygenation rat astrocytes.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Scutellarin (Scu) and caffeic acid ester fraction
      (Caf), the extracts from the traditional Chinese herb, Erigeron breviscapus, are
      known to ameliorate post ischemic neuronal dysfunction. AIM OF THE STUDY:
      Neurotrophic factors (NTFs) are essential for neuronal growth and survival. We
      explored the neuroprotective effect of Scu and Caf by synthesis and release of
      NGF, BDNF and GDNF in rat astrocytes exposed to hypoxia/reoxygenation and MACO
      rats. And the neuroprotection of Scu and Caf was also explored. MATERIALS AND
      METHODS: The primary rat astrocytes were cultured in vitro. The temporal mRNA and
      protein expression profile during hypoxia/reoxygenation were analyzed using real
      time RT-PCR and ELISA. The expression of p-CREB, p-Akt, p-MAPKs and Bax were
      analyzed by western blotting. Cell viability of neuro-2A was measured using CCK-8
      and cell cytotoxicity was measured with LDH release. RESULTS: During
      hypoxia/reoxygenation a similar decrease pattern of NTFs (NGF, BDNF and GDNF) was
      observed in both mRNA and protein; Scu and Caf enhanced the expressions of NGF,
      BDNF and GDNF mRNA and protein in astrocytes under hypoxia/reoxygenation
      condition. CREB and Akt, but not MAPKs ( p-JNK, p-ERK1/2 and p-38) may be
      involved in the expression of NTFs. Concomitantly, conditioned medium from
      astrocytes which was treated by Scu or Caf after hypo3h/Reox24h significantly
      reduced neurotoxicity compared with conditioned medium from hypo3h/Reox24h
      astrocytes alone, and they show the tendency of increased neurons viability
      accompanied with Bax changes. CONCLUSIONS: These results indicate that the
      neuroprotective effect of Scu and Caf might be mediated, at least in part, via a
      stimulation of the production and release of NTFs through p-CREB and p-Akt
      signaling. Furthermore, Scu and Caf could antagonistic the hypoxia induced
      toxicity through astrocytes conditioned medium. Those results suggested that Scu
      and Caf might have therapeutic potential for stroke.

PMID- 24012968
TI  - Development and evaluation of a loop-mediated isothermal amplification assay for
      diagnosis of Cyprinid herpesvirus 2.
AB  - Goldfish Haematopoietic Necrosis caused by Cyprinid herpesvirus 2 (CyHV-2) is a
      severe fish disease with high level of mortality. This is the first study on
      detection of this disease by loop-mediated isothermal amplification (LAMP). A set
      of six primers targeting terminase gene (accession no. EU349285.1) was determined
      after a serial of tests. Detection limit was 1.09 * 10(-4)MUg/MUL, which was
      superior to conventional PCR and real-time PCR. No cross reaction with 28 other
      viruses or bacteria commonly found in fish was observed. The application of
      commercial kit and instrument for the LAMP assay could reduce the risk of cross
      contamination, which is suitable for detection of infection under field
      conditions.

PMID- 24012967
TI  - Eriosema laurentii De Wild (Leguminosae) methanol extract has estrogenic
      properties and prevents menopausal symptoms in ovariectomized Wistar rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Eriosema laurentii De Wild (Leguminosae) is a
      medicinal plant used in West and Central Africa for different diseases. In
      Cameroon, this plant is used as a treatment for infertility, and various
      gynecological and menopausal complaints. However, despite this use as a natural
      remedy, the biological activity of Eriosema laurentii has not been studied until
      now. AIM OF STUDY: In order to determine the potential use of this plant in
      gynecological conditions/disorders, we evaluated the estrogenic properties of a
      methanol extract of its aerial parts and its ability to prevent different
      menopausal health problems induced by bilateral oophorectomy. MATERIAL AND
      METHODS: Two approaches were used. In vitro, recombinant yeast systems were
      applied, featuring either the respective human receptors (ERalpha, AR, and PR) or
      into chromosome III integrated human aryl hydrocarbon receptor (AhR) and the
      respective reporter plasmid. In vivo, the investigation was carried out using the
      3 days uterotrophic assay and 9 weeks oral treatment in ovariectomized rats.
      RESULTS: The results showed that the methanol extract of the aerial parts of
      Eriosema laurentii transactivated the estrogen receptor-alpha and displayed AhR
      agonistic activity but was neither androgenic nor progesteronic. In rats, the
      extract did not induce endometrium proliferation either in the 3-day or the 9
      week treatment regimens, but induced vaginal stratification and cornification,
      prevented loss of femur bone mass, increased high density lipoprotein cholesterol
      (HDL-C), and reduced total cholesterol (TC), low density lipoprotein cholesterol
      (LDL-C), TC/HDL-C ratio, LDL-C/HDL-C ratio and the atherogenic index of plasma
      (AIP). CONCLUSION: These results suggest that the methanol extract of the aerial
      parts of Eriosema laurentii does not seem to have an undesirable influence on the
      endometrium but might prevent vaginal dryness and bone mass loss and improve the
      lipid profile.

PMID- 24012969
TI  - PCR-based approach to distinguish group A human rotavirus genotype 1 vs. genotype
      2 genes.
AB  - Group A rotaviruses (RVs) are eleven-segmented, double-stranded RNA viruses and
      important causes of severe diarrhea in children. A full-genome classification
      system is readily used to describe the genetic makeup of individual RV strains.
      In this system, each viral gene is assigned a specific genotype based upon its
      nucleotide sequence and established percent identity cut-off values. However, a
      faster and more cost-effective approach to determine RV gene genotypes is to
      utilize specific oligonucleotide primer sets in RT-PCR/PCR. Such primer sets and
      PCR-based genotyping methods have already been developed for the VP7-, VP6-, VP4-
      and NSP4-coding gene segments. In this study, primers were developed for the
      remaining seven RV gene segments, which encode proteins VP1, VP2, VP3, NSP1,
      NSP2, NSP3, and NSP5/6. Specifically, primers were designed to distinguish the
      two most common human RV genotypes (1 vs. 2) for these genes and were validated
      on several cell culture-adapted human and animal RV strains, as well as on human
      RVs from clinical fecal specimens. As such, primer sets now exist for all eleven
      genes of common human RVs, allowing for the identification of reassortant strains
      with mixed constellations of both genotype 1 and 2 genes using a rapid and
      economical RT-PCR/PCR method. 

PMID- 24012970
TI  - Brain regional cannabinoid CB(1) receptor signalling and alternative enzymatic
      pathways for 2-arachidonoylglycerol generation in brain sections of
      diacylglycerol lipase deficient mice.
AB  - Endocannabinoids are the endogenous ligands of the G protein-coupled cannabinoid
      receptors. The principal brain endocannabinoid, 2-arachidonoylglycerol (2-AG), is
      enzymatically produced by postsynaptic neurons and then activates presynaptic CB1
      receptors in a retrograde manner. The primary pathway for 2-AG generation is
      believed to be conversion from the diacylglycerols (DAGs) by two sn-1-specific
      lipases, DAGLalpha and DAGLbeta. Previous studies with DAGL-deficient mice
      indicated that DAGLalpha is the major enzyme needed for retrograde synaptic 2-AG
      signalling. The current study investigated whether the CB1 receptor-mediated Gi/o
      protein activity is altered in brain cryosections of DAGL-deficient mice when
      compared to wild-type mice and whether the sn-1-specific DAGLs are able to
      generate 2-AG in brain cryosections. Functional autoradiography indicated that
      brain regional CB1 receptor-Gi/o-activity largely remained unaltered in DAGLalpha
      knockout and DAGLbeta-knockout mice when compared to wild-type littermates.
      Following comprehensive pharmacological blockade of 2-AG hydrolysis, brain
      sections generated sufficient amounts of 2-AG to activate CB1 receptors
      throughout the regions endowed with these receptors. As demonstrated by LC/MS/MS,
      this pool of 2-AG was generated via tetrahydrolipstatin-sensitive enzymatic
      pathways distinct from DAGLalpha or DAGLbeta. We conclude that in addition to the
      sn-1-specific DAGLs, additional 2-AG generating enzymatic pathways are active in
      brain sections. 

PMID- 24012971
TI  - Development of sandwich ELISAs for the detection of aromatic diisocyanate
      adducts.
AB  - Diisocyanates (dNCOs) are highly reactive low molecular weight chemicals commonly
      used in the manufacturing industry. Occupational exposures to dNCOs have been
      shown to elicit allergic sensitization and occupational asthma. Among the most
      commonly used dNCOs in industry are the aromatic dNCOs, toluene diisocyanate
      (TDI) and methylene diphenyl diisocyanate (MDI). This study aimed to develop
      enzyme linked immunosorbent assays (ELISA) utilizing aromatic dNCO-specific
      monoclonal antibodies (mAbs) for the detection of aromatic dNCO adducts. Two
      sandwich ELISAs were developed. The first sandwich ELISA utilized mAb 60G2 along
      with an anti-human serum albumin (HSA) polyclonal antibody. This assay detected
      MDI-, 2,4- and 2,6-TDI-HSA adducts with limits of detection (LOD) of 2.67, <0.10,
      and 1.70 ng/mL, respectively. When spiked into human serum, the LOD of this ELISA
      increased to 34.37, 7.64 and 24.06 ng/mL, respectively. The second ELISA utilized
      mAbs 62G5 and 60G2 for capture and detection. This assay was capable of detecting
      2,4- and 2,6-TDI-HSA adducts with LODs of <4.90 and 26.92 ng/mL, respectively,
      and when spiked in human serum, <4.90 and 95.93 ng/mL, respectively. This 62G5
      60G2 sandwich assay was also able to detect dNCO adducted transferrin,
      hemoglobin, keratin and actin, but with less sensitivity than dNCO-HSA. The
      results of this study demonstrate potential application of these ELISAs in the
      identification and characterization of aromatic dNCO adducts as well as in
      biomonitoring occupational and environmental dNCO exposures.

PMID- 24012972
TI  - Potential drug interventions for diabetic retinopathy.
AB  - Diabetic retinopathy (DR) is of great interest to the drug discovery community
      owing to the rising worldwide prevalence of diabetes and its associated
      complications. The complex molecular mechanism associated with DR development and
      the poor translatability of available animal models to late-stage DR are
      considered to be major hurdles for drug discovery. Here we will provide an
      overview of the mechanistic rationale as well as clinical efficacy of drug
      candidates, and highlight emerging and potential targets for therapeutic
      intervention at different stages of DR. 

PMID- 24012973
TI  - Solution equilibria of cytosine- and guanine-rich sequences near the promoter
      region of the n-myc gene that contain stable hairpins within lateral loops.
AB  - BACKGROUND: Cytosine- and guanine-rich regions of DNA are capable of forming
      complex structures named i-motifs and G-quadruplexes, respectively. In the
      present study the solution equilibria at nearly physiological conditions of a 34
      base long cytosine-rich sequence and its complementary guanine-rich strand
      corresponding to the first intron of the n-myc gene were studied. Both sequences,
      not yet studied, contain a 12-base tract capable of forming stable hairpins
      inside the i-motif and G-quadruplex structures, respectively. METHODS:
      Spectroscopic, mass spectrometry and separation techniques, as well as
      multivariate data analysis methods, were used to unravel the species and
      conformations present. RESULTS: The cytosine-rich sequence forms two i-motifs
      that differ in the protonation of bases located in the loops. A stable Watson
      Crick hairpin is formed by the bases in the first loop, stabilizing the i-motif
      structure. The guanine-rich sequence adopts a parallel G-quadruplex structure
      that is stable throughout the pH range 3-7, despite the protonation of cytosine
      and adenine bases at lower pH values. The presence of G-quadruplex aggregates was
      confirmed using separation techniques. When mixed, G-quadruplex and i-motif
      coexist with the Watson-Crick duplex across a pH range from approximately 3.0 to
      6.5. CONCLUSIONS: Two cytosine- and guanine-rich sequences in n-myc gene may form
      stable i-motif and G-quadruplex structures even in the presence of long loops. pH
      modulates the equilibria involving the intramolecular structures and the
      intermolecular Watson-Crick duplex. GENERAL SIGNIFICANCE: Watson-Crick hairpins
      located in the intramolecular G-quadruplexes and i-motifs in the promoter regions
      of oncogenes could play a role in stabilizing these structures.

PMID- 24012974
TI  - The 'order-to-disorder' conformational transition in CD44 protein: an umbrella
      sampling analysis.
AB  - The molecule of CD44, a membrane protein being the major cell surface receptor
      for hyaluronan, is postulated to undergo the conformational rearrangement called
      the 'order-to-disorder' transition. The experimental studies suggest that the
      Tyr161 residue is crucial for maintaining the equilibrium between the 'ordered'
      (O) and 'partially disordered' (PD) forms of CD44. The molecular modeling study
      based on the umbrella sampling protocol was carried out separately for the wild
      type CD44 and Tyr161Ala mutant in order to gain more insight into the molecular
      mechanism of the O-PD transition and to clarify the role of the Tyr161 amino acid
      residue. The calculated free energy profiles associated with the initial stages
      of the O-PD conformational transition allow to identify the crucial steps of this
      process and their molecular details. The differences between the wild-type CD44
      and the Tyr161Ala mutant are very insignificant which allows for speculating
      that, surprisingly, the role of Tyr161 in the O-PD transition is not connected
      with disrupting the attractive Glu48-Tyr161 and Leu52-Tyr161 interactions but
      with other types of (unknown yet) interactions located outside the beta7-beta8
      loop or with the existence of the PD-like structure in which the terminal lobe
      remains located under the beta7-beta8 loop. 

PMID- 24012975
TI  - A comparative quality appraisal of finely comminuted batters produced using three
      types of knives.
AB  - The aim of this study was to compare the work efficiency of three types of knives
      mounted successively on a knife roll of a cutter by evaluating the quality and
      structure of produced finely comminuted batters as well as power consumption and
      electric energy consumption during chopping. Experimental material comprised
      finely comminuted meat batters produced under commercial scale production
      conditions using smooth knives, knives with riffles and knives with holes.
      Parameters measured in batter included temperature, water, fat, free water,
      apparent viscosity, thermal drip and batter structure using computer image
      analysis. Computer image analysis showed that the best comminution and dispersion
      of fat globules in the protein matrix together with very good comminution of
      collagen fibres were observed at the application of knives with holes. Among the
      three types of knives used in the production of finely comminuted meat batters
      the best batter in terms of its quality and structure was produced using knives
      with holes. 

PMID- 24012976
TI  - In vitro evaluation of antimicrobial activities of various commercial essential
      oils, oleoresin and pure compounds against food pathogens and application in ham.
AB  - The purpose of this research was to evaluate the application of commercially
      available essential oils (EOs) and oleoresins to control bacterial pathogens for
      ready to eat food. In this study, sixty seven commercial EOs, oleoresins (ORs)
      and pure compounds were used to evaluate in vitro their antimicrobial activity
      against six food pathogens. These products were first screened for their
      antimicrobial activity using disk diffusion assay. Forty one products were then
      chosen for further analysis to determine their minimum inhibitory concentration
      against 6 different bacteria. There were 5 different products (allyl
      isothiocyanate, cinnamon Chinese cassia, cinnamon OR, oregano and red thyme) that
      showed high antimicrobial activity against all tested bacteria. Further analysis
      examined the effect of four selected EOs on controlling the growth rate of mixed
      cultures of Listeria monocytogenes in ham. A reduction of the growth rate by 19
      and 10% was observed when oregano and cinnamon cassia EOs were respectively added
      in ham at a concentration of 500 ppm.

PMID- 24012977
TI  - Flaxseed fed pork: n-3 fatty acid enrichment and contribution to dietary
      recommendations.
AB  - The potential to increase n-3 fatty acid (FA) intake via flaxseed fed pork is
      underestimated when restricted to pure longissimus muscle, whereas a combination
      of muscle and adipose tissue is typically consumed. Presently, the FA content of
      pigs fed 0%, 5% and 10% dietary flaxseed for 11 weeks was measured in loin,
      picnic and butt primals (lean muscle with epimysium (L), L plus seam fat (LS),
      and LS plus 5 mm backfat (LSS)). The n-3 FA content necessary for an enrichment
      claim in Canada (300 mg/100 g serving) was exceeded in L from all primals when
      feeding 5% flaxseed, being 4 fold that of controls (P<0.001), with further
      enrichment from inclusion of associated adipose tissues (P<0.001). Increasing
      flaxseed feeding levels in combination with adipose tissue inclusion amplified
      total long chain n-3 FA (P<0.05), particularly 20:5n-3 and 22:5n-3. Flaxseed-fed
      n-3 FA enriched pork can contribute substantially to daily long chain n-3 FA
      intakes, particularly for societies with typically low seafood consumption.

PMID- 24012978
TI  - Mitochondrial targeting functional peptides as potential devices for the
      mitochondrial delivery of a DF-MITO-Porter.
AB  - To achieve mitochondrial therapy, we previously reported on the use of an
      octaarginine (R8) modified Dual Function (DF)-MITO-Porter for delivering
      molecules to mitochondria in living cells. In this study, using isolated
      mitochondria, homogenates and living cells, we evaluated the utility of
      mitochondrial targeting functional peptides as a ligand for delivering carriers.
      The S2 peptide modified carrier showed a high mitochondrial targeting activity in
      homogenates and living cells. In addition, the S2 peptide had a lower cell
      toxicity compared to R8 modified liposomes. The S2 peptide represents a
      potentially useful moiety for constructing an efficient and safe mitochondrial
      delivery system. 

PMID- 24012979
TI  - Classification of diesel pool refinery streams through near infrared spectroscopy
      and support vector machines using C-SVC and nu-SVC.
AB  - The use of near infrared (NIR) spectroscopy combined with chemometric methods
      have been widely used in petroleum and petrochemical industry and provides
      suitable methods for process control and quality control. The algorithm support
      vector machines (SVM) has demonstrated to be a powerful chemometric tool for
      development of classification models due to its ability to nonlinear modeling and
      with high generalization capability and these characteristics can be especially
      important for treating near infrared (NIR) spectroscopy data of complex mixtures
      such as petroleum refinery streams. In this work, a study on the performance of
      the support vector machines algorithm for classification was carried out, using C
      SVC and nu-SVC, applied to near infrared (NIR) spectroscopy data of different
      types of streams that make up the diesel pool in a petroleum refinery: light gas
      oil, heavy gas oil, hydrotreated diesel, kerosene, heavy naphtha and external
      diesel. In addition to these six streams, the diesel final blend produced in the
      refinery was added to complete the data set. C-SVC and nu-SVC classification
      models with 2, 4, 6 and 7 classes were developed for comparison between its
      results and also for comparison with the soft independent modeling of class
      analogy (SIMCA) models results. It is demonstrated the superior performance of
      SVC models especially using nu-SVC for development of classification models for 6
      and 7 classes leading to an improvement of sensitivity on validation sample sets
      of 24% and 15%, respectively, when compared to SIMCA models, providing better
      identification of chemical compositions of different diesel pool refinery
      streams. 

PMID- 24012980
TI  - Spectroscopic (FT-IR, FT-Raman), first order hyperpolarizability, NBO analysis,
      HOMO and LUMO analysis of 2,4-bis(2-methoxyphenyl)-1-phenylanthracene-9,10-dione
      by ab initio HF and density functional methods.
AB  - Anthraquinone derivatives are most important class of a system that absorb in the
      visible region. In this work, the vibrational spectral analysis was carried out
      using FT-IR and FT-Raman spectroscopy for 2,4-bis(2-methoxyphenyl)-1
      phenylanthracene-9,10-dione. Theoretical calculations were performed by ab initio
      HF and DFT methods using 6-31G(*) basis set. The complete vibrational assignments
      of wavenumbers were made on the basis of potential energy distribution. The HOMO
      and LUMO analysis is used to determine the charge transfer within the molecule.
      The stability of the molecule arising from hyper-conjugative interaction and
      charge delocalization has been analyzed using NBO analysis. The calculated
      geometrical parameters (DFT) are in agreement with that of similar derivatives.
      The calculated first hyperpolarizability of the title compound is 4.69*10(-30)
      esu, which is 36.08 times that of urea and the title compound and the series of
      compounds it represents are attractive candidates for further studies in non
      linear optical applications.

PMID- 24012981
TI  - Synthesis and application of surface-imprinted activated carbon sorbent for solid
      phase extraction and determination of copper (II).
AB  - A new Cu(II)-imprinted amino-functionalized activated carbon sorbent was prepared
      by a surface imprinting technique for selective solid-phase extraction (SPE) of
      Cu(II) prior to its determination by inductively coupled plasma atomic emission
      spectrometry (ICP-AES). Experimental conditions for effective adsorption of
      Cu(II) were optimized with respect to different experimental parameters using
      static and dynamic procedures in detail. Compared with non-imprinted sorbent, the
      ion-imprinted sorbent had higher selectivity and adsorption capacity for Cu(II).
      The maximum static adsorption capacity of the ion-imprinted and non-imprinted
      sorbent for Cu(II) was 26.71 and 6.86 mg g(-1), respectively. The relatively
      selectivity factor values (alphar) of Cu(II)/Zn(II), Cu(II)/Ni(II), Cu(II)/Co(II)
      and Cu(II)/Pb(II) were 166.16, 50.77, 72.26 and 175.77, respectively, which were
      greater than 1. Complete elution of the adsorbed Cu(II) from Cu(II)-imprinted
      sorbent was carried out using 2 mL of 0.1 mol L(-1) EDTA solution. The relative
      standard deviation of the method was 2.4% for eleven replicate determinations.
      The method was validated for the analysis by two certified reference materials
      (GBW 08301, GBW 08303), the results obtained is in good agreement with standard
      values. The developed method was also successfully applied to the determination
      of trace copper in natural water samples with satisfactory results.

PMID- 24012982
TI  - Reduced risk of colorectal cancer up to 10 years after screening, surveillance,
      or diagnostic colonoscopy.
AB  - BACKGROUND & AIMS: Data from randomized controlled trials on the effects of
      screening colonoscopies on colorectal cancer (CRC) incidence and mortality are
      not available. Observational studies have suggested that colonoscopies strongly
      reduce the risk of CRC, but there is little specific evidence on the effects of
      screening colonoscopies. METHODS: We performed a population-based case-control
      study of 3148 patients with a first diagnosis of CRC (cases) and 3274 subjects
      without CRC (controls) from the Rhine-Neckar region of Germany from 2003 to 2010.
      Detailed information on previous colonoscopy and potential confounding factors
      was collected by standardized personal interviews. Self-reported information on
      colonoscopies and their indications was validated by medical records. We used
      multiple logistic regression to assess the association between colonoscopy
      conducted for specific indications within the past 10 years and risk of CRC.
      RESULTS: A history of colonoscopy was associated with a reduced subsequent risk
      of CRC, independently of the indication for the examination. However, somewhat
      stronger associations were found for examinations with screening indications
      (adjusted odds ratio [OR] 0.09, 95% confidence interval [CI] 0.07-0.13) than for
      examinations with diagnostic indications, such as positive fecal occult blood
      test result (OR, 0.33; 95% CI, 0.19-0.57), surveillance after a preceding
      colonoscopy (OR, 0.33; 95% CI, 0.24-0.45), rectal bleeding (OR, 0.28; 95% CI,
      0.20-0.40), abdominal symptoms (OR, 0.15; 95% CI, 0.10-0.21), or other (OR, 0.21;
      95% CI, 0.14-0.30). Colonoscopy was also associated with a reduced risk of cancer
      in the right colon, regardless of the indication, although to a smaller extent
      than for other areas of the colon (OR for screening colonoscopy, 0.22; 95% CI,
      0.14-0.33). CONCLUSIONS: In a population-based case-control study, the risk of
      CRC was strongly reduced up to 10 years after colonoscopy for any indication.
      Risk was particularly low after screening colonoscopy, even for cancer in the
      right colon.

PMID- 24012983
TI  - Aspiration therapy leads to weight loss in obese subjects: a pilot study.
AB  - BACKGROUND & AIMS: Obese patients rarely achieve long-term weight loss with only
      lifestyle interventions. We evaluated the use of endoscopic aspiration therapy
      for obesity. Aspiration therapy involves endoscopic placement of a gastrostomy
      tube (A-Tube) and the AspireAssist siphon assembly (Aspire Bariatrics, King of
      Prussia, PA) to aspirate gastric contents 20 minutes after meal consumption.
      METHODS: We performed a pilot study of 18 obese subjects who were randomly
      assigned (2:1) to groups that underwent aspiration therapy for 1 year plus
      lifestyle therapy (n = 11; mean body mass index, 42.6 +/- 1.4 kg/m(2)) or
      lifestyle therapy only (n = 7; mean body mass index, 43.4 +/- 2.0 kg/m(2)).
      Lifestyle intervention comprised a 15-session diet and behavioral education
      program. RESULTS: Ten of the 11 subjects who underwent aspiration therapy and 4
      of the 7 subjects who underwent lifestyle therapy completed the first year of the
      study. After 1 year, subjects in the aspiration therapy group lost 18.6% +/- 2.3%
      of their body weight (49.0% +/- 7.7% of excess weight loss [EWL]) and those in
      the lifestyle therapy group lost 5.9% +/- 5.0% (14.9% +/- 12.2% of EWL) (P <
      .04). Seven of the 10 subjects in the aspiration therapy group completed an
      additional year of therapy and maintained a 20.1% +/- 3.5% body weight loss
      (54.6% +/- 12.0% of EWL). There were no adverse effects of aspiration therapy on
      eating behavior and no evidence of compensation for aspirated calories with
      increased food intake. No episodes of binge eating in the aspiration therapy
      group or serious adverse were reported. CONCLUSIONS: In a pilot study, aspiration
      therapy appears to be a safe and effective long-term weight loss therapy for
      obesity.

PMID- 24012985
TI  - Adult olfactory sphere cells are a source of oligodendrocyte and Schwann cell
      progenitors.
AB  - The olfactory epithelial layer contains multipotent horizontal basal cells (HBCs)
      that differentiate into olfactory sensory neurons. Here, we show that rat HBCs
      express oligodendrocyte progenitor cell (OPC) and astrocyte markers. We generated
      olfactory sphere (OS) cells in cultures that were derived from adult rat
      olfactory mucosa. Fluorescence-activated cell sorting and immunofluorescence
      analyses showed that OS cells also express OPC and astrocyte markers.
      Interestingly, OS cells underwent oligodendrocyte differentiation in vitro. To
      study oligodendrocyte differentiation in vivo, OS cells were transplanted into
      injured rat spinal cords. The transplanted cells integrated into host tissue and
      differentiated into oligodendrocytes. When transected saphenous nerve ends were
      encased in collagen-containing silicone tubes with or without OS cells, the
      transplanted OS cells differentiated into Schwann cells. Our data provide new
      insights into of the stemness of OS cells. 

PMID- 24012986
TI  - ERK1/2 pathway is activated in degenerated Rpe65-deficient mice.
AB  - The MAPK family is composed of three majors kinases, JNK, p38 and ERK1/2, and is
      implicated in many degenerative processes, including retinal cell death. The
      purpose of our study was to evaluate the activation of ERK1/2 kinase, and its
      potential role in Muller cell gliosis, during photoreceptor cell death in Rpe65(
      /-) mice. We assayed ERK1/2 mRNA and protein levels, and evaluated ERK1/2
      phosphorylation involved in kinase activation, in 2, 4 and 6 month-old Rpe65(-/-)
      mice and in age-matched wild-type controls. No differences in ERK1/2 expression
      were detected between Rpe65(-/-) and wild-type mice, however, ERK1/2
      phosphorylation was dramatically increased in the knock out mice at 4 and 6
      months-of-age. Phosphorylated ERK1/2 co-localized with GFAP in the ganglion cell
      layer, and correlated with an increase in GFAP protein expression and retinal
      cell death. Accumulation of cFOS protein in the ganglion cell layer occurred
      concomitant with pERK1/2 activation. Muller cell proliferation was not observed.
      ERK1/2 activation did not occur in 2 month-old Rpe65(-/-) or in the Rpe65(-/
      )/Gnat1(-/-) mice, in which no degeneration was evident. The observed activation
      ERK1/2 and GFAP, both markers of Muller cell gliosis, in the absence of Muller
      cell proliferation, is consistent with the activation of atypical gliosis
      occurring during the slow process of degeneration in Rpe65(-/-) mice. As Muller
      cell gliosis is activated in many neuronal and retinal degenerative diseases,
      further studies will be needed to determine whether atypical gliosis in Rpe65(-/
      ) mice contributes to, or protects against, the pathogenesis occurring in this
      model of Leber congenital amaurosis. 

PMID- 24012984
TI  - Genome-wide methylation analysis and epigenetic unmasking identify tumor
      suppressor genes in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Epigenetic silencing of tumor suppressor genes contributes to
      the pathogenesis of hepatocellular carcinoma (HCC). To identify clinically
      relevant tumor suppressor genes silenced by DNA methylation in HCC, we integrated
      DNA methylation data from human primary HCC samples with data on up-regulation of
      gene expression after epigenetic unmasking. METHODS: We performed genome-wide
      methylation analysis of 71 human HCC samples using the Illumina HumanBeadchip27K
      array; data were combined with those from microarray analysis of gene re
      expression in 4 liver cancer cell lines after their exposure to reagents that
      reverse DNA methylation (epigenetic unmasking). RESULTS: Based on DNA methylation
      in primary HCC and gene re-expression in cell lines after epigenetic unmasking,
      we identified 13 candidate tumor suppressor genes. Subsequent validation led us
      to focus on functionally characterizing 2 candidates, sphingomyelin
      phosphodiesterase 3 (SMPD3) and neurofilament, heavy polypeptide (NEFH), which we
      found to behave as tumor suppressor genes in HCC. Overexpression of SMPD3 and
      NEFH by stable transfection of inducible constructs into an HCC cell line reduced
      cell proliferation by 50% and 20%, respectively (SMPD3, P = .003 and NEFH, P =
      .003). Conversely, knocking down expression of these genes with small hairpin RNA
      promoted cell invasion and migration in vitro (SMPD3, P = .0001 and NEFH, P =
      .022), and increased their ability to form tumors after subcutaneous injection or
      orthotopic transplantation into mice, confirming their role as tumor suppressor
      genes in HCC. Low levels of SMPD3 were associated with early recurrence of HCC
      after curative surgery in an independent patient cohort (P = .001; hazard ratio =
      3.22; 95% confidence interval: 1.6-6.5 in multivariate analysis). CONCLUSIONS:
      Integrative genomic analysis identified SMPD3 and NEFH as tumor suppressor genes
      in HCC. We provide evidence that SMPD3 is a potent tumor suppressor gene that
      could affect tumor aggressiveness; a reduced level of SMPD3 is an independent
      prognostic factor for early recurrence of HCC.

PMID- 24012987
TI  - Diet, nutraceuticals and the tear film.
AB  - Nutrition disorders and their correlates such as obesity are increasingly
      prevalent worldwide. A number of studies to date have suggested numerous
      potential associations between diet and tear film health; this paper will provide
      a summary of the available literature. The tear film is characterized through its
      protein and lipid content and through clinical measurements of characteristics
      such as osmolarity, volume and stability. Malnutrition, protein and vitamin-A
      deficiencies are extremely deleterious to tear film health and supplementation
      with oral vitamin A in this setting is of clear benefit. The relative impact of
      diet on tear film within what would be considered normal ranges of consumption is
      less clear. A number of population studies have suggested that hyperlipidemia and
      a diet low in omega-3 fatty acids are risks factor for dry eye disease. Numerous
      studies have investigated the effectiveness of oral supplementation with
      antioxidants, omega-3 (e.g. fish oil and linseed oil) and omega-6 (e.g. evening
      primrose oil) fatty acids in the last 10 years. Taken together, these suggest a
      small benefit of oral supplementation on tear film volume, stability and
      decreased ocular symptoms in patients previously diagnosed with diseases
      involving the ocular surface (e.g. Sjogren's syndrome, meibomian gland
      dysfunction, dry eye disease) and contact lens wearers suffering from dry eye.
      More research is required to determine the exact composition, dosage and
      indications for their use and to fully characterize how these nutraceuticals
      modulate the tear film. 

PMID- 24012988
TI  - Autophagy and mitophagy participate in ocular lens organelle degradation.
AB  - The eye lens consists of a layer of epithelial cells that overlay a series of
      differentiating fiber cells that upon maturation lose their mitochondria, nuclei
      and other organelles. Lens transparency relies on the metabolic function of
      mitochondria contained in the lens epithelial cells and in the immature fiber
      cells and the programmed degradation of mitochondria and other organelles
      occurring upon lens fiber cell maturation. Loss of lens mitochondrial function in
      the epithelium or failure to degrade mitochondria and other organelles in lens
      fiber cells results in lens cataract formation. To date, the mechanisms that
      govern the maintenance of mitochondria in the lens and the degradation of
      mitochondria during programmed lens fiber cell maturation have not been fully
      elucidated. Here, we demonstrate using electron microscopy and dual-label
      confocal imaging the presence of autophagic vesicles containing mitochondria in
      lens epithelial cells, immature lens fiber cells and during early stages of lens
      fiber cell differentiation. We also show that mitophagy is induced in primary
      lens epithelial cells upon serum starvation. These data provide evidence that
      autophagy occurs throughout the lens and that mitophagy functions in the lens to
      remove damaged mitochondria from the lens epithelium and to degrade mitochondria
      in the differentiating lens fiber cells for lens development. The results provide
      a novel mechanism for how mitochondria are maintained to preserve lens metabolic
      function and how mitochondria are degraded upon lens fiber cell maturation. 

PMID- 24012989
TI  - Swimmers can train in hypoxia at sea level through voluntary hypoventilation.
AB  - This study used an innovative technique of pulse oximetry to investigate whether
      swimmers can train under hypoxic conditions through voluntary hypoventilation
      (VH). Ten trained subjects performed a front crawl swimming series with normal
      breathing (NB), VH at high (VHhigh) and low pulmonary volume (VHlow). Arterial
      oxygen saturation was continuously measured via pulse oximetry (SpO2) with a
      waterproofed forehead sensor. Gas exchanges were recorded continuously and
      lactate concentration ([La]) was assessed at the end of each test. In VHlow, SpO2
      fell down to 87% at the end of the series whereas it remained above 94% in VHhigh
      during most part of the series. Ventilation, oxygen uptake and end-tidal O2
      pressure were lower in both VHhigh and VHlow than in NB. Compared to NB, [La]
      significantly increased in VHlow and decreased in VHhigh. This study demonstrated
      that swimmers can train under hypoxic conditions at sea level and can accentuate
      the glycolytic stimulus of their training if they perform VH at low but not high
      pulmonary volume. 

PMID- 24012990
TI  - Importance of mitochondrial P(O2) in maximal O2 transport and utilization: a
      theoretical analysis.
AB  - In previous calculations of how the O2 transport system limits .VO2(max), it was
      reasonably assumed that mitochondrial P(O2) (Pm(O2)) could be neglected (set to
      zero). However, in reality, Pm(O2) must exceed zero and the red cell to
      mitochondrion diffusion gradient may therefore be reduced, impairing diffusive
      transport of O2 and .VO2(max). Accordingly, we investigated the influence of
      Pm(O2) on these calculations by coupling previously used equations for O2
      transport to one for mitochondrial respiration relating mitochondrial .VO2 to
      P(O2). This hyperbolic function, characterized by its P50 and VMAX, allowed
      Pm(O2) to become a model output (rather than set to zero as previously).
      Simulations using data from exercising normal subjects showed that at .VO2(max),
      Pm(O2) was usually <1mmHg, and that the effects on .VO2(max) were minimal.
      However, when O2 transport capacity exceeded mitochondrial VMAX, or if P50 were
      elevated,Pm(O2) often reached double digit values, thereby reducing the diffusion
      gradient and significantly decreasing .VO2(max).

PMID- 24012991
TI  - Differences in the pattern of bronchoconstriction induced by intravenous and
      inhaled methacholine in rabbit.
AB  - We measured bronchoconstriction in central bronchi, and in small peripheral
      airways causing the emergence of ventilation defects (VD), through two delivery
      routes: intravenous (IV) and inhaled MCh, in 2 groups of rabbits (A: n=5; B:
      n=4), using synchrotron imaging of regional lung structure and ventilation. We
      assessed the effect an initial IV challenge on a subsequent inhaled challenge in
      group B. Inhaled MCh decreased central airway cross-sections (CA) by 13-22%, but
      increased VD area by 25-49%. IV MCh decreased CA by 44% but increased the area of
      ventilation defects (VD) by 13% only. An initial IV MCh challenge reduced
      regional ventilation heterogeneity following a subsequent inhaled MCh challenge,
      suggesting the role of agonist-receptor interaction in the response pattern.
      Heterogeneous agonist distribution due to uneven aerosol deposition could explain
      the different patterns of response between IV and inhaled routes. This mechanism
      could participate in the emergence of ventilation heterogeneities during
      bronchial challenge, or exposure to allergen in asthmatic patients. 

PMID- 24012993
TI  - Late-life fecundity plateaus in Drosophila melanogaster can be explained by
      variation in reproductive life spans.
AB  - Population trajectories of age-specific fecundity in Drosophila melanogaster
      typically decline with increasing age and then exhibit an upward inflection, or
      "plateau", at the oldest ages. This pattern has been interpreted as evidence of
      an evolved and physiologically distinct life history stage in late life. While
      low levels of fecundity are common in the last few days of life of individual
      flies, it is unclear that defining a single age as the beginning of a period of
      low fecundity for the entire cohort is useful, since reproductive life spans vary
      substantially from fly to fly. Here I analyze published data on survival and
      reproduction of individual female flies and show that non-linearities in late
      life fecundity trajectories arise from a type of demographic selection that
      occurs when sub-groups with different reproductive life spans (RLS) are mixed.
      For groups of flies stratified by RLS late-life fecundity declines linearly with
      age. A simulation incorporating strictly linear decline of individual fecundities
      and realistic levels of variation in RLS produces late-life plateaus similar to
      those observed in experiments. Existing population heterogeneity is a sufficient
      explanation, and no special evolutionary argument is required. For these data
      survival and reproduction are governed by positive correlations. 

PMID- 24012992
TI  - Oleanolic acid improves pulmonary morphofunctional parameters in experimental
      sepsis by modulating oxidative and apoptotic processes.
AB  - We compared the effects of oleanolic acid (OA) vs. dexamethasone on lung
      mechanics and histology, inflammation, and apoptosis in lung and distal organs in
      experimental sepsis. Seventy-eight BALB/c mice were randomly divided into two
      groups. Sepsis was induced by cecal ligation and puncture, while the control
      group underwent sham surgery. 1h after surgery, all animals were further
      randomized to receive saline (SAL), OA and dexamethasone (DEXA)
      intraperitoneally. Both OA and DEXA improved lung mechanics and histology, which
      were associated with fewer lung neutrophils and less cell apoptosis in lung,
      liver, and kidney than SAL. However, only animals in the DEXA group had lower
      levels of interleukin (IL)-6 and KC (murine analog of IL-8) in bronchoalveolar
      lavage fluid than SAL animals. Conversely, OA was associated with lower inducible
      nitric oxide synthase expression and higher superoxide dismutase than DEXA. In
      the experimental sepsis model employed herein, OA and DEXA reduced lung damage
      and distal organ apoptosis through distinct anti-inflammatory mechanisms. 

PMID- 24012994
TI  - Age-induced perturbation in cell membrane phospholipid fatty acid profile of
      longevity-selected Drosophila melanogaster and corresponding control lines.
AB  - Various compositions of fatty acids can produce cell membranes with disparate
      fluidity and propensity for oxidation. The latter characteristic, which can be
      evaluated via the peroxidation index (PI), has a fundamental role in the
      development of the "membrane-pacemaker theory" of aging. This study tried to
      evaluate differences between the membrane phospholipid fatty acid (PLFA) profile
      of longevity-selected (L) and corresponding control (C) lines of Drosophila
      melanogaster with age (3, 9, 14 and 19 days) and its consequences on phase
      transition temperature as a function of membrane fluidity. Despite an equal
      proportion of polyunsaturated fatty acids, PI and double bond index over all ages
      in both experimental groups, monounsaturated fatty acids showed significant
      variation with advancement of age in both L and C lines. A significant age
      associated elevation of the unsaturation vs. saturation index in parallel with a
      gradual reduction of the mean melting point was observed in longevous flies. PLFA
      composition of the L vs. C lines revealed a dissimilarity in 3-day old samples,
      which was based on the positive loading of C(14:0) and C(18:3) as well as
      negative loading of C(18:0). The findings of this study are not in agreement with
      the principle of the "membrane pacemaker theory" linking PI and longevity.
      However, the physiochemical properties of PLFAs in longevity lines may retard the
      cells' senescence by maintaining optimal membrane functionality over time.
      Identical susceptibility to peroxidation of both types of lines underlines the
      involvement of other mechanisms in protecting the bio-membrane against oxidation,
      such as the reduced production of mitochondrial reactive oxygen species or
      improvement of the antioxidant defense system in longer-lived phenotypes.
      Concurrent assessments of these mechanisms in relation to cell membrane PLFA
      composition may clarify the cellular basis of lifespan in this species.

PMID- 24012995
TI  - Male-to-female transfer of 5-hydroxytryptophan glucoside during mating in Zygaena
      filipendulae (Lepidoptera).
AB  - Zygaena filipendulae accumulates the cyanogenic glucosides linamarin and
      lotaustralin by larval sequestration from the food plant or de novo biosynthesis.
      We have previously demonstrated that the Z. filipendulae male transfers linamarin
      and lotaustralin to the female in the course of mating. In this study we report
      the additional transfer of 5-hydroxytryptophan glucoside (5-(beta-d
      glucopyranosyloxy)-L-Tryptophan) from the Z. filipendulae male internal genitalia
      to the female spermatophore around 5 h into the mating process. 5
      Hydroxytryptophan glucoside is present in the virgin male internal genitalia, and
      production continues during the early phase of mating. Following initiation of 5
      hydroxytryptophan glucoside transfer to the female, the amount in male internal
      genitalia is drastically reduced until after mating where it is slowly
      replenished. For unambiguous structural identification, 5-hydroxytryptophan
      glucoside was chemically synthesized and used as an authentic standard. The
      biological function of 5-hydroxytryptophan glucoside remains to be established,
      although we have indications that it may be involved in inducing the female to
      stay in copula and delay egg-laying to prevent re-mating of the female. To our
      knowledge 5-hydroxytryptophan glucoside has not previously been reported present
      in animal tissues.

PMID- 24012996
TI  - From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses.
AB  - This article introduces a series of invited papers in Antiviral Research marking
      the 10th anniversary of the outbreak of severe acute respiratory syndrome (SARS),
      caused by a novel coronavirus that emerged in southern China in late 2002. Until
      that time, coronaviruses had not been recognized as agents causing severe disease
      in humans, hence, the emergence of the SARS-CoV came as a complete surprise.
      Research during the past ten years has revealed the existence of a diverse pool
      of coronaviruses circulating among various bat species and other animals,
      suggesting that further introductions of highly pathogenic coronaviruses into the
      human population are not merely probable, but inevitable. The recent emergence of
      another coronavirus causing severe disease, Middle East respiratory syndrome
      (MERS), in humans, has made it clear that coronaviruses pose a major threat to
      human health, and that more research is urgently needed to elucidate their
      replication mechanisms, identify potential drug targets, and develop effective
      countermeasures. In this series, experts in many different aspects of coronavirus
      replication and disease will provide authoritative, up-to-date reviews of the
      following topics: - clinical management and infection control of SARS; -
      reservoir hosts of coronaviruses; - receptor recognition and cross-species
      transmission of SARS-CoV; - SARS-CoV evasion of innate immune responses; -
      structures and functions of individual coronaviral proteins; - anti-coronavirus
      drug discovery and development; and - the public health legacy of the SARS
      outbreak. Each article will be identified in the last line of its abstract as
      belonging to the series "From SARS to MERS: 10years of research on highly
      pathogenic human coronaviruses." 

PMID- 24012997
TI  - The impact of weight loss on the 24-h profile of circulating peptide YY and its
      association with 24-h ghrelin in normal weight premenopausal women.
AB  - Peptide YY (PYY) and ghrelin exhibit a reciprocal association and antagonistic
      physiological effects in the peripheral circulation. Research has yet to clarify
      the effect of weight loss on the 24h profile of PYY or its association to 24h
      ghrelin. We sought to determine if diet- and exercise-induced weight loss affects
      the 24h profile of PYY and its association with 24h ghrelin in normal weight,
      premenopausal women. Participants (n = 13) were assessed at baseline (BL) and
      after a 3-month diet and exercise intervention (post). Blood samples obtained q10
      min for 24h were assayed for total PYY and total ghrelin q60 min from 0800 to
      1000 h and 2000 to 0800 h and q20 min from 1000 to 2000 h. The ghrelin/PYY ratio
      was used as an index of hormonal exposure. Statistical analyses included paired t
      tests and linear mixed effects modeling. Body weight (-1.85 +/- 0.67 kg; p =
      0.02), and body fat (-2.53 +/- 0.83%; p = 0.01) decreased from BL to post.
      Ghrelin AUC (5252 +/- 2177 pg/ml/24h; p=0.03), 24h mean (216 +/- 90 pg/ml; p =
      0.03) and peak (300 +/- 134 pg/ml; p = 0.047) increased from BL to post. No
      change occurred in PYY AUC (88.2 +/- 163.7 pg/ml; p = 0.60), 24h mean (4.8 +/-
      6.9 pg/ml; p = 0.50) or peak (3.6 +/- 6.4 pg/ml; p = 0.58). The 24h association
      between PYY and ghrelin at baseline (p = 0.04) was weakened at post (p = 0.14);
      however, the ghrelin/PYY lunch ratio increased (p = 0.01) indicating the
      potential for ghrelin predominance over PYY in the circulation. PYY and ghrelin
      are reciprocally associated during a period of weight stability, but not
      following weight loss. An "uncoupling" may have occurred, particularly at lunch,
      due to factors that modulate ghrelin in response to weight loss.

PMID- 24012998
TI  - Predictors of survival in hepatitis B virus related decompensated cirrhosis on
      tenofovir therapy: an Indian perspective.
AB  - Decompensated cirrhosis has low survival rate compared to compensated state.
      Effective viral suppression due to antiviral therapy (tenofovir) has been shown
      to slow disease progression and may delay the burden of liver transplantation. We
      aimed to evaluate the usefulness of various prognostic indicators in predicting
      the 24-months survival in HBV related decompensated cirrhosis after tenofovir
      therapy and to evaluate the post-treatment outcome. Ninety-six HBV related
      decompensated patients on antiviral (tenofovir) therapy were prospectively
      studied for 24months survival and mortality. Cutoff levels for several prognostic
      indicators were generated by ROC. Prediction of overall probability of mortality
      was also calculated. The overall probability of survival observed at 12months was
      0.947 whereas at 24months it was found to be 0.833. According to Cox proportional
      hazards model, the univariate analysis revealed cutoff of >7.4logcopies/ml for
      HBV DNA, >1.2mg/dl for serum creatinine, >3.7mg/dl for total bilirubin, ?0.75 for
      platelets count, >10 for CTP and >20 for MELD as predictors of poor survival.
      Multivariate analysis showed MELD score of >20 was the most robust predictor of
      mortality, with 58 times higher risk (HR: 58.73, p<0.001). Post-treatment
      response with tenofovir for 24months significantly improved the hepatic functions
      and reverses decompensation and showed incredible efficacy in improvement of
      hepatic functional status with reduced viremia in a great majority of
      decompensated cirrhosis subjects having high MELD and HBV DNA level. 

PMID- 24012999
TI  - Synthetic analogues of bovine bactenecin dodecapeptide reduce herpes simplex
      virus type 2 infectivity in mice.
AB  - We have evaluated the potential of four synthetic peptides (denoted HH-2, 1002,
      1006, 1018) with a distant relationship to the host defense peptide bovine
      bactenecin dodecapeptide for their ability to prevent genital infections with
      herpes simplex virus type 2 (HSV-2) in mice. All four peptides showed antiviral
      properties in vitro and reduced HSV-2 infection of Vero cells in a dose-dependent
      manner. Detailed analysis showed that the peptides were able to interfere with
      both viral attachment and entry, but not with replication post-entry, and were
      effective antivirals also when HSV-2 was introduced in human semen. Two of the
      peptides proved especially effective in reducing HSV-2 infection also in vivo.
      When admixed with virus prior to inoculation, both HH-2 and 1018 reduced viral
      replication and disease development in a genital model of HSV-2 infection in
      mice, and also when using very high infectious doses of HSV-2. These data show
      that peptides HH-2 and 1018 have antiviral properties and can be used to prevent
      genital herpes infection in mice. 

PMID- 24013001
TI  - In vitro efficacy of approved and experimental antivirals against novel genotype
      3 hepatitis C virus subgenomic replicons.
AB  - Infection with genotype 3 hepatitis C virus (HCV) is common throughout the world,
      however no direct-acting antiviral (DAA) has been approved to treat this
      genotype. We therefore attempted to develop novel genotype 3 replicons to
      facilitate the discovery and development of new HCV therapies. A novel Huh-7
      derived cell line 1C but not Lunet cells enabled the selection of a few stable
      colonies of a genotype 3a subgenomic replicon (strain S52). Genotypic analysis
      revealed a mutation of P89L in the viral NS3 protease domain, which was confirmed
      to enhance genotype 3a RNA replication and enable the establishment of highly
      replicating luciferase-encoding replicons. Secondary adaptive mutations that
      further enhanced RNA replication were identified in the viral NS3 and NS4A
      proteins. In addition, cell lines that were cured of genotype 3a replicons
      demonstrated higher permissiveness specifically to genotype 3a HCV replication.
      These novel replicons and cell lines were then used to study the activity of
      approved and experimental HCV inhibitors. NS3 protease and non-nucleoside NS5B
      polymerase inhibitors often demonstrated substantially less antiviral activity
      against genotype 3a compared to genotype 1b. In contrast, nucleoside analog NS5B
      inhibitors and host-targeting HCV inhibitors showed comparable antiviral activity
      between genotypes 3a and 1b. Overall, the establishment of this novel genotype 3a
      replicon system, in conjunction with those derived from other genotypes, will aid
      the development of treatment regimens for all genotypes of HCV. 

PMID- 24013002
TI  - Development and characterization of a replicon-based phenotypic assay for
      assessing HCV NS4B from clinical isolates.
AB  - The hepatitis C virus (HCV) NS4B inhibitors have shown potent inhibition of HCV
      replication in vitro. To assess the effect of viral diversity on the
      susceptibility to NS4B inhibitors, genotype (GT)-specific GT1a and GT1b replicon
      shuttle vectors were designed and created for cloning HCV NS4B genes from
      clinical isolates. For the GT1b NS4B shuttle vector, the S2204I adaptive mutation
      was introduced in NS5A to improve replication due to the replacement of the
      K1846T adaptive mutation in NS4B with NS4B from the clinical isolates. In
      addition to the adaptive mutations, a newly identified Huh-7 cell line, Huh-7-1C,
      which is highly permissive for both GT1a and GT1b replication, was used to
      further enhance the replication levels. HCV NS4B gene from clinical isolates was
      amplified and inserted into the corresponding GT1a and GT1b modified lab strain
      chimeric replicons. GT1a and GT1b chimeric replicons expressing diverse NS4B
      genes from corresponding subtypes of clinical isolates replicated at highly
      efficient levels for phenotypic analysis. Due to natural variation in their amino
      acid residues in NS4B, these isolates displayed varying drug susceptibilities to
      an NS4B inhibitor. In mixed populations with wild-type, the sensitivity of
      resistance detection of NS4B resistant mutants H94R and V105M was between 20% and
      80%. The chimeric shuttle vectors can be used to characterize the activity of
      antiviral drugs targeting NS4B from diverse natural clinical isolates and aid in
      the development of novel compounds against HCV NS4B. 

PMID- 24013000
TI  - Neuraminidase inhibitors for influenza B virus infection: efficacy and
      resistance.
AB  - Many aspects of the biology and epidemiology of influenza B viruses are far less
      studied than for influenza A viruses, and one of these aspects is efficacy and
      resistance to the clinically available antiviral drugs, the neuraminidase (NA)
      inhibitors (NAIs). Acute respiratory infections are one of the leading causes of
      death in children and adults, and influenza is among the few respiratory
      infections that can be prevented and treated by vaccination and antiviral
      treatment. Recent data has suggested that influenza B virus infections are of
      specific concern to pediatric patients because of the increased risk of severe
      disease. Treatment of influenza B is a challenging task for the following
      reasons: This review presents current knowledge of the efficacy of NAIs for
      influenza B virus and antiviral resistance in clinical, surveillance, and
      experimental studies. 

PMID- 24013003
TI  - Identification and characterization of defensin genes from the endoparasitoid
      wasp Cotesia vestalis (Hymenoptera: Braconidae).
AB  - Defensins are members of a large and diverse family of antimicrobial peptides
      (AMPs) containing three or four intramolecular disulfide bonds. They are widely
      distributed from vertebrates to invertebrates, and serve as critical defense
      molecules protecting the host from the invasion of pathogens or protozoan
      parasites. Cotesia vestalis is a small endoparasitoid wasp that lays eggs in
      larvae of Plutella xylostella, a cosmopolitan pest of cruciferous crops. We
      identified and characterized three full-length cDNAs encoding putative defensin
      like peptides from C. vestalis, named CvDef1, CvDef2 and CvDef3. Phylogenetic
      analyses of these sequences showed that they are present in two clades, CITDs and
      PITDs, indicating a diversity of defensins in C. vestalis. We analyzed their
      expression patterns in larvae, pupae and adults by semi-quantitative RT-PCR. The
      results showed that CvDef1 mRNA was expressed from the end stage of the second
      instar larva, CvDef3 mRNA from the early stage of the second instar larva, and
      CvDef2 mRNA was expressed in all developmental stages of C. vestalis.
      Furthermore, CvDef1 showed antimicrobial activity against gram-positive and gram
      negative bacteria. Growth kinetics of Staphylococcus aureus indicated that CvDef1
      had much better antimicrobial ability than ampicillin, making it a potential
      candidate for practical use. Transmission electron microscopic (TEM) examination
      of CvDef1-treated S. aureus cells showed extensive damage to the cell membranes.
      Our results revealed the basic properties of three defensins in C. vestalis for
      the first time, which may pave the way for further study of the functions of
      defensins in parasitism and innate immunity of C. vestalis. 

PMID- 24013004
TI  - Brain metabolism and oxygenation in healthy pigs receiving hypoventilation and
      hyperoxia.
AB  - Modulation in ventilatory settings is one of the approaches and interventions
      used to treat and prevent secondary brain damage after traumatic brain injury
      (TBI). Here we investigate the effect of hyperoxia in combination with
      hypoventilation on brain oxygenation, metabolism and intracranial pressure.
      Twelve pigs were divided into three groups; group1-100% hyperoxia (n=4), group 2
      100% hyperoxia and 20% decrease in minute volume (MV) (n=4) and group 3-100%
      hyperoxia and 50% decrease in MV (n=4). Neither of the ventilator settings
      affected the lactate/pyruvate ratio significantly. However, there was a
      significant decrease of brain lactate (2.6+/-1.7 to 1.8+/-1.6mM) and a rapid and
      marked increase in brain oxygenation (7.9+/-0.7 to 61.3+/-17.6mmHg) in group 3.
      Intracranial pressure (ICP) was not significantly affected in this group,
      however, the ICP increased significantly in group 2 with 100% hyperoxia plus 20%
      reduction in minute volume. We conclude that hyperoxia in combination with 50%
      decrease in MV showed pronounced increase in partial brain oxygen tension (pbrO2)
      and decrease in brain lactate. The ventilatory modification, used in this study
      should be considered for further investigation as a possible therapeutic
      intervention for TBI patients. 

PMID- 24013005
TI  - Activity monitoring reflects cardiovascular and metabolic variations in COPD
      patients across GOLD stages II to IV.
AB  - We investigated whether activity monitoring reliably reflects variations in
      oxygen transport and utilization during walking in COPD patients. Forty-two
      patients (14 in each GOLD stage II, III and IV) performed an incremental
      treadmill protocol to the limit of tolerance. Breath-by-breath gas exchange,
      central hemodynamic variables and activity monitoring were simultaneously
      recorded. Physiological variables and accelerometer outputs rose linearly with
      walking speeds. Strong correlations (r[interquartile range, IQR]) were found
      between treadmill walking intensity (WI: range 0.8-2.0 ms(-2)) and oxygen
      consumption (0.95 [IQR 0.87-0.97]), (range 7.6-15.5 ml kg(-1)min(-1)); minute
      ventilation (0.95 [IQR 0.86-0.98]), (range 20-37 l min(-1)); cardiac output (0.89
      [IQR 0.73-0.94]), (range 6.8-11.5 l min(-1)) and arteriovenous oxygen
      concentration difference (0.84 [IQR 0.76-0.90]), (range 7.7-12.1 ml O2100 ml(
      1)). Correlations between WI and gas exchange or central hemodynamic parameters
      were not different across GOLD stages. In conclusion, central hemodynamic,
      respiratory and muscle metabolic variations during incremental treadmill exercise
      are tightly associated to changes in walking intensity as recorded by
      accelerometry across GOLD stages II to IV. Interestingly, the magnitude of these
      associations is not different across GOLD stages.

PMID- 24013006
TI  - Treatment of pregnant BALB/c mice with sulphadoxine pyrimethamine or chloroquine
      abrogates Plasmodium berghei induced placental pathology.
AB  - Malaria infection during pregnancy is a risk factor for foetus survival and is
      associated with abortion, premature delivery and low birth weight of infants in
      malaria endemic regions. In these regions, prophylactic measures and treatment
      mainly rely on chloroquine and sulphadoxine pyrimethamine, but their efficacy in
      reducing the placental pathology has not been studied. Therefore, the present
      study was designed to assess the effectiveness of chloroquine and sulphadoxine
      pyrimethamine treatment in reducing the placental pathology of Plasmodium berghei
      infected BALB/c mice. It was observed that pregnant-infected mice, treated either
      with chloroquine or sulphadoxine pyrimethamine had significantly lower percent
      parasitaemia, 100% survival and delivered normally compared with untreated
      pregnant-infected mice. Interestingly, antimalarial treatment significantly
      reduced malondialdehyde (MDA) levels, measure of lipid peroxidation and number of
      apoptotic cells in the placentae of pregnant-infected treated mice.
      Histologically also no morphological and cellular alterations were observed in
      the placentae of pregnant-infected treated mice. Taken together, the study shows
      the effectiveness of chloroquine and sulphadoxine pyrimethamine treatment, when
      administered in second trimester in abrogating malaria induced oxidative stress,
      apoptosis and histopathological alterations in the placenta, leading to normal
      foetal development. 

PMID- 24013007
TI  - A transcriptomic analysis on gene expressions in the infective third and
      pathogenic fifth larval stages of Angiostrongylus cantonensis.
AB  - Although Angiostrongylus cantonensis is a parasite of rats, it is an important
      etiologic agent of eosinophilic meningitis and eosinophilic meningoencephalitis
      in humans. This study was designed to compare the gene expression in the third-
      and fifth-stage (L3 and L5) by analysis of expressed sequence tags (ESTs). After
      removing low quality sequences, vector trimming, clustering and contig assembly,
      there remained 1437 clusters (285 contigs and 1152 singletons). Among these
      clusters, 779 (54.2%) showed significant similarity to the known proteins in the
      non-redundant protein database of GenBank (E-value<1*10(-10)) and species of the
      best hit sequences mainly belonged to nematodes. These clusters included 869
      (60.5%) that were entirely comprised of ESTs from L3 (L3-biased clusters), 518
      (36.0%) entirely from L5 (L5-biased clusters) and 50 (3.5%) from both stages
      (stage-shared clusters). Functional annotations by the Gene Ontology (GO)
      comparing with the eukaryotic clusters of orthologous groups of proteins (KOG)
      indicate that the L3-biased clusters significantly related to metabolism and the
      L5-biased clusters to growth, development, sexual differentiation and
      reproduction. Moreover, L3 were found to have expressions of metalloproteases,
      aspartic proteases, and cysteine proteases whereas expressions of cysteine,
      aspartic and serine proteases were revealed in L5. The results indicate that
      earlier developmental stages of nematodes may have a gene expression profile
      towards metabolism and later stages towards growth and development. 

PMID- 24013008
TI  - Suppression of outward K+ currents by WIN55212-2 in rat retinal ganglion cells is
      independent of CB1/CB2 receptors.
AB  - Cannabinoid CB1 receptor (CB1R) signaling system is extensively distributed in
      the vertebrate retina. Activation of CB1Rs regulates a variety of functions of
      retinal neurons through modulating different ion channels. In the present work we
      studied effects of this receptor signaling on K(+) channels in retinal ganglion
      cells by patch-clamp techniques. The CB1R agonist WIN55212-2 (WIN) suppressed
      outward K(+) currents in acutely isolated rat retinal ganglion cells in a dose
      dependent manner, with an IC50 of 4.7 MUM. We further showed that WIN mainly
      suppressed the tetraethylammonium (TEA)-sensitive K(+) current component. While
      CB1Rs were expressed in rat retinal ganglion cells, the WIN effect on K(+)
      currents was not blocked by either AM251/SR141716, specific CB1R antagonists, or
      AM630, a selective CB2R antagonist. Consistently, cAMP-protein kinase A (PKA) and
      mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase
      (ERK) signaling pathways were unlikely involved in the WIN-induced suppression of
      the K(+) currents because both PKA inhibitors H-89/Rp-cAMP and MAPK/ERK1/2
      inhibitor U0126 failed to block the WIN effects. WIN-induced suppression of the
      K(+) currents was not observed when WIN was intracellularly applied. Furthermore,
      an endogenous ligand of the cannabinoid receptor anandamide, the specific CB1R
      agonist ACEA and the selective CB2R agonist CB65 also suppressed the K(+)
      currents, and the effects were not blocked by AM251/SR141716 or AM630
      respectively. All these results suggest that the WIN-induced suppression of the
      outward K(+) currents in rat retinal ganglion cells, thereby regulating the cell
      excitability, were not through CB1R/CB2R signaling pathways.

PMID- 24013009
TI  - Cortisol analysis of hair of captive chimpanzees (Pan troglodytes).
AB  - In addition to behavioral evaluations, stress assessments are also important for
      measuring animal welfare. Assessments of long-term stress are particularly
      important given that prolonged stress can affect physical health and
      reproduction. The use of hair cortisol as a marker of long-term stress has been
      increasing, but there has not yet been any report on the use of such methods with
      chimpanzees. Therefore, the purpose of this study was to establish and validate a
      methodology for analyzing hair cortisol in captive chimpanzees. In the first
      experiment, hair was removed from the arms of nine chimpanzees living in the
      Kumamoto Sanctuary (KS) and the regrown hair was sampled 3 months later. Fecal
      samples were collected periodically during the hair-growth period. The results
      showed that hair cortisol level was positively correlated with the rate of
      receiving aggression. Although the correlation between hair and fecal cortisol
      levels was not significant, the individual with the highest hair cortisol
      concentration also had the highest fecal cortisol concentration. These results
      suggest that hair cortisol may reflect long-term stress in chimpanzees. In the
      second experiment, we investigated the physiological factors affecting hair
      cortisol concentrations. We cut hair from the arms, sides, and backs of 25
      chimpanzees living at the KS and the Primate Research Institute. The results
      revealed that cortisol varied based on source body part and hair whiteness.
      Therefore, we recommend that hair should always be collected from the same body
      part and that white hair should be avoided as much as possible.

PMID- 24013010
TI  - The chloroplast signal recognition particle (CpSRP) pathway as a tool to minimize
      chlorophyll antenna size and maximize photosynthetic productivity.
AB  - The concept of the Truncated Light-harvesting chlorophyll Antenna (TLA) size, as
      a tool by which to maximize sunlight utilization and photosynthetic productivity
      in microalgal mass cultures or high-density plant canopies, is discussed. TLA
      technology is known to improve sunlight-to-product energy conversion efficiencies
      and is hereby exemplified by photosynthetic productivity estimates of wild type
      and a TLA strain under simulated mass culture conditions. Recent advances in the
      generation of TLA-type mutants by targeting genes of the chloroplast signal
      recognition particle (CpSRP) pathway, affecting the thylakoid membrane assembly
      of light-harvesting proteins, are also summarized. Two distinct CpSRP assembly
      pathways are recognized, one entailing post-translational, the other a co
      translational mechanism. Differences between the post-translational and co
      translational integration mechanisms are outlined, as these pertain to the CpSRP
      mediated assembly of thylakoid membrane protein complexes in higher plants and
      green microalgae. The applicability of the CpSRP pathway genes in efforts to
      generate TLA-type strains with enhanced solar energy conversion efficiency in
      photosynthesis is evaluated. 

PMID- 24013012
TI  - FGF2 blocks PTSD symptoms via an astrocyte-based mechanism.
AB  - Although posttraumatic stress disorder (PTSD) is characterized by traumatic
      memories or experiences and increased arousal, which can be partly alleviated by
      antidepressants, the underlying cellular mechanisms are not fully understood. As
      emerging studies have focused on the critical role of astrocytes in pathological
      mood disorders, we hypothesized that several 'astrocyte-related' mechanisms
      underlying PTSD exist. In the present study, using the single prolonged stress
      (SPS) model, we investigated the effects of intraperitoneal FGF2 on SPS-induced
      PTSD behavior response as well as the astrocytic activation after FGF2
      administration in SPS rats. Behavioral data showed that intraperitoneal FGF2
      inhibited SPS-induced hyperarousal and anxiety behavior; however,
      immunohistochemistry showed that SPS-induced astrocytic inhibition was activated
      by intraperitoneal FGF2. Quantitative western blotting showed that
      intraperitoneal FGF2 up-regulated glial fibrillary acidic protein (GFAP), but not
      NeuN, expression in the hippocampus. We suggest that intraperitoneal FGF2 could
      block the SPS-induced fear response and anxiety behavior in PTSD via astrocyte
      based but not neuron-based mechanisms. 

PMID- 24013013
TI  - Reappraisal of spontaneous stereotypy in the deer mouse as an animal model of
      obsessive-compulsive disorder (OCD): response to escitalopram treatment and basal
      serotonin transporter (SERT) density.
AB  - Obsessive-compulsive disorder (OCD) is characterized by recurrent thoughts and
      repetitive motor actions. Hyposerotonergic signalling in the cortico-striatal
      circuitry is believed to be central to the pathology of OCD, while many patients
      only respond to chronic treatment with high dose selective serotonin (5HT)
      reuptake inhibitors (SSRIs). Confined deer mice spontaneously develop two forms
      of stereotypy, namely vertical jumping and pattern running. The purpose of this
      investigation was to reappraise these behaviours and strengthen the validity of
      deer mouse stereotypy as an animal model of OCD within a framework of three study
      questions: (1) can the time spent executing stereotypical behaviours be employed
      as a measure of extent of stereotypy, (2) does deer mouse stereotypy only respond
      to chronic, but not sub-chronic treatment with a high-dose SSRI, and (3) is deer
      mouse stereotypy associated with altered cortico-striatal 5HT transporter (SERT)
      binding? The current study demonstrates that treatment naive high stereotypical
      (HS) deer mice spend significantly more time executing stereotypical behaviours
      while significantly less time is spent indulging in stereotypy following chronic,
      but not sub-chronic, treatment with escitalopram. Furthermore, HS deer mice
      present with a significant decrease in striatal SERT density compared to non
      stereotypical (NS) controls. Building on previous validation studies, we conclude
      that deer mouse stereotypy is a valid naturalistic animal model of OCD with
      robust face, construct and predictive validity. 

PMID- 24013011
TI  - Rigid nanoparticle-based delivery of anti-cancer siRNA: challenges and
      opportunities.
AB  - Gene therapy is a promising strategy to treat various genetic and acquired
      diseases. Small interfering RNA (siRNA) is a revolutionary tool for gene therapy
      and the analysis of gene function. However, the development of a safe, efficient,
      and targetable non-viral siRNA delivery system remains a major challenge in gene
      therapy. An ideal delivery system should be able to encapsulate and protect the
      siRNA cargo from serum proteins, exhibit target tissue and cell specificity,
      penetrate the cell membrane, and release its cargo in the desired intracellular
      compartment. Nanomedicine has the potential to deal with these challenges faced
      by siRNA delivery. The unique characteristics of rigid nanoparticles mostly
      inorganic nanoparticles and allotropes of carbon nanomaterials, including high
      surface area, facile surface modification, controllable size, and excellent
      magnetic/optical/electrical properties, make them promising candidates for
      targeted siRNA delivery. In this review, recent progresses on rigid nanoparticle
      based siRNA delivery systems will be summarized. 

PMID- 24013014
TI  - Sympathetic denervation of peri-infarct myocardium requires the p75 neurotrophin
      receptor.
AB  - Development of cardiac sympathetic heterogeneity after myocardial infarction
      contributes to ventricular arrhythmias and sudden cardiac death. Regions of
      sympathetic hyperinnervation and denervation appear in the viable myocardium
      beyond the infarcted area. While elevated nerve growth factor (NGF) is implicated
      in sympathetic hyperinnervation, the mechanisms underlying denervation are
      unknown. Recent studies show that selective activation of the p75 neurotrophin
      receptor (p75(NTR)) in sympathetic neurons causes axon degeneration. We used mice
      that lack p75(NTR) to test the hypothesis that activation of p75(NTR) causes peri
      infarct sympathetic denervation after cardiac ischemia-reperfusion. Wild type
      hearts exhibited sympathetic denervation adjacent to the infarct 24h and 3 days
      after ischemia-reperfusion, but no peri-infarct sympathetic denervation occurred
      in p75(NTR)-/- mice. Sympathetic hyperinnervation was found in the distal peri
      infarct myocardium in both genotypes 3 days after MI, and hyperinnervation was
      increased in the p75(NTR)-/- mice. By 7 days after ischemia-reperfusion, cardiac
      sympathetic innervation density returned back to sham-operated levels in both
      genotypes, indicating that axonal pruning did not require p75(NTR). Prior studies
      revealed that proNGF is elevated in the damaged left ventricle after ischemia
      reperfusion, as is mRNA encoding brain-derived neurotrophic factor (BDNF). ProNGF
      and BDNF preferentially bind p75(NTR) rather than TrkA on sympathetic neurons.
      Immunohistochemistry using Bdnf-HA mice confirmed the presence of BDNF or proBDNF
      in the infarct after ischemia-reperfusion. Thus, at least two p75(NTR) ligands
      are elevated in the left ventricle after ischemia-reperfusion where they may
      stimulate p75(NTR)-dependent denervation of peri-infarct myocardium. In contrast,
      NGF-induced sympathetic hyperinnervation in the distal peri-infarct ventricle is
      attenuated by p75(NTR).

PMID- 24013016
TI  - Radon emanation fractions from concretes containing fly ash and metakaolin.
AB  - Radon ((222)Rn) and progenies emanate from soil and building components and can
      create an indoor air quality hazard. In this study, nine concrete constituents,
      including the supplementary cementitious materials (SCMs) fly ash and metakaolin,
      were used to create eleven different concrete mixtures. We investigated the
      effect of constituent radium specific activity, radon effective activity and
      emanation fraction on the concrete emanation fraction and the radon exhalation
      rate. Given the serious health effects associated with radionuclide exposure,
      experimental results were coupled with Monte Carlo simulations to demonstrate
      predictive differences in the indoor radon concentration due to concrete mixture
      design. The results from this study show that, on average, fly ash constituents
      possessed radium specific activities ranging from 100 Bq/kg to 200 Bq/kg and
      emanation fractions ranging from 1.1% to 2.5%. The lowest emitting concrete
      mixture containing fly ash resulted in a 3.4% reduction in the concrete emanation
      fraction, owing to the relatively low emanation that exists when fly ash is part
      of concrete. On average, the metakaolin constituents contained radium specific
      activities ranging from 67 Bq/kg to 600 Bq/kg and emanation fractions ranging
      from 8.4% to 15.5%, and changed the total concrete emanation fraction by roughly
      +/-5% relative to control samples. The results from this study suggest that SCMs
      can reduce indoor radon exposure from concrete, contingent upon SCM
      radionucleotide content and emanation fraction. Lastly, the experimental results
      provide SCM-specific concrete emanation fractions for indoor radon exposure
      modeling.

PMID- 24013015
TI  - Repeated intravenous doxapram induces phrenic motor facilitation.
AB  - Doxapram is a respiratory stimulant used to treat hypoventilation. Here we
      investigated whether doxapram could also trigger respiratory neuroplasticity.
      Specifically, we hypothesized that intermittent delivery of doxapram at low doses
      would lead to long-lasting increases (i.e., facilitation) of phrenic motor output
      in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was
      delivered intravenously in a single bolus (2 or 6mg/kg) or as a series of 3
      injections (2mg/kg) at 5min intervals. Control groups received pH-matched saline
      injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked
      an immediate increase in phrenic output in all groups, but a persistent increase
      in burst amplitude only occurred after repeated dosing with 2mg/kg. At 60min
      following the last injection, phrenic burst amplitude was 168+/-24% of baseline
      (%BL) in the group receiving 3 injections (P<0.05 vs. controls), but was 103+/
      8%BL and 112+/-4%BL in the groups receiving a single dose of 2 or 6mg/kg,
      respectively. Following bilateral section of the carotid sinus nerves, the acute
      phrenic response to doxapram (2mg/kg) was reduced by 68% suggesting that at low
      doses the drug was acting primarily via the carotid chemoreceptors. We conclude
      that intermittent application of doxapram can trigger phrenic neuroplasticity,
      and this approach might be of use in the context of respiratory rehabilitation
      following neurologic injury. 

PMID- 24013017
TI  - Facilitated attachment of nanoparticles at primary minima by nanoscale roughness
      is susceptible to hydrodynamic drag under unfavorable chemical conditions.
AB  - This study investigated effects of flow velocity on attachment of nanoparticles
      at primary minima in the presence of surface roughness under unfavorable chemical
      conditions. Saturated sand-packed column experiments were conducted at 0.1 and
      0.2M NaCl using 30 nm polystyrene latex nanoparticles as model colloids. Particle
      attachment at primary minima was unambiguously determined by removing particles
      attached at secondary minima through introducing deionized water and excavating
      the packed beds. The calculated primary-minimum attachment efficiency was found
      to decrease with increasing flow velocity, indicating that the fraction of a
      collector surface that is available for attachment at primary minima decreases
      with increasing flow velocity. The torque analysis, however, showed that the
      adhesive torque that the particle experiences at primary minima is much larger
      than the maximum hydrodynamic drags of a porous medium for the flow velocities
      used. We attributed the discrepancy to the reason that the sand surface is very
      rough and the roughness mainly causes the attachment in primary minima under the
      experimental conditions used in this study. By considering influence of surface
      roughness in the torque analysis, our calculations show that while particle
      attachment in primary minima is favored atop of nanoasperities under unfavorable
      conditions, the adhesive torque that the particle experiences can be greatly
      reduced and, thus, the attachment is susceptible to flow drag. Whereas the
      increase of adhesive torque by surface roughness has been widely recognized in
      the literature, our study indicates that the rough asperities can also decrease
      adhesive torques for particles attached atop of them.

PMID- 24013018
TI  - In silico characterization and evolutionary analyses of CCAAT binding proteins in
      the lycophyte plant Selaginella moellendorffii genome: a growing comparative
      genomics resource.
AB  - NF-Y transcription factors encoded by HAP gene family, composed of three subunits
      (HAP2/NF-YA, HAP3/NF-YB and HAP5/NF-YC), are capable of transcriptional
      regulation of target genes with high specificity by binding to the CCAAT
      containing promoter sequences. Here, we have characterized duplicated HAP genes
      in Selaginella moellendorffii and explored some features that might be involved
      in the regulation of gene expression and their function. Subsequently, the
      evolutionary relationships of LEC1-type of HAP3 genes have been studied starting
      from lycophytes to angiosperm to reveal the details of conservation and
      diversification of these genes during plant evolution. Computational analyses
      demonstrated the variation in length of cis-regulatory region of HAP3 duplicates
      in S. moellendorffii containing three thermodynamically stable and evolutionarily
      conserved RNA secondary structures. The homology modeling of NF-Y proteins,
      secondary structural details, DNA binding large positive patches, binding
      affinity of H2A-H2B interactive residues of NF-YC subunits on the duplicated NF
      YB subunits, conserved domain analyses and protein structural alignments
      indicated that gene duplication process of HAP genes in S. moellendorffii,
      followed by structural diversification, provide specific hints about their
      functional specificity under various circumstances for the survival of this
      lycophytic plant. We have identified several conserved motifs in LEC1 proteins
      among all plant lineages during evolution. 

PMID- 24013019
TI  - Are the parasiticidal avermectins resistant to dissipation in the environment?
      The case of eprinomectin.
AB  - Eprinomectin (EPM) is a veterinary drug currently licensed in many countries for
      the treatment of endo- and ecto-parasites in cattle. Despite the notable evidence
      for its high toxicity to the terrestrial and aquatic environment ecosystems, its
      environmental behavior and fate are currently unknown. In the present research,
      the dissipation of EPM was studied in three soils and in cattle manure by using
      the OECD 307 guideline and the recently developed European Medicines Agency
      (EMA/CVMP/ERA/430327) guideline, respectively. The procedure presented by the
      FOrum for Co-ordination of pesticide models and their USe (FOCUS) was adopted for
      estimating the EPM degradation kinetics in soil and cattle manure. The EPM
      dissipation in soil was best described by the SFO (Simple First Order) and the HS
      (Hockey Stick) models, under aerobic and anaerobic conditions, respectively. The
      EPM dissipation in cattle manure was best described by the FOMC (First Order
      Multi Compartment) model. The Dissipation Time for the 50% of the initial EPM
      mass (DT50) range was 38-53days under aerobic and 691-1491days under anaerobic
      conditions. In addition, the DT50 for EPM in cattle manure was 333days.
      Therefore, EPM could be characterized as moderately to highly persistent to
      dissipation in soil, which depends on soil type, its oxygen content (aerobic or
      anaerobic conditions in soil) and the microbial activity. Moreover, the EPM
      resists dissipation in cattle manure, resulting to a high load in soil after
      manure application in agricultural land (or direct defecation in grassland).
      Consequently, the high possibility for EPM accumulation in soil and cattle manure
      should be considered when assessing the environmental risk of the drug. 

PMID- 24013020
TI  - Potentially harmful elements (PHEs) in scalp hair, soil and metallurgical wastes
      in Mitrovica, Kosovo: the role of oral bioaccessibility and mineralogy in human
      PHE exposure.
AB  - Internationally publicized impacts upon human health associated with potentially
      harmful element (PHE) exposure have been reported amongst internally displaced
      populations (IDPs) in Mitrovica, Kosovo, following the Kosovan War. Particular
      concern has surrounded the exposure to Pb indicated by the presence of highly
      elevated concentrations of Pb in blood and hair samples. This study utilizes a
      physiologically-based in-vitro extraction method to assess the bioaccessibility
      of PHEs in surface soils and metallurgical waste in Mitrovica and assesses the
      potential daily intake of soil-bound PHEs. Maximum As (210mgkg(-1)), Cd (38mgkg(
      1)), Cu (410mgkg(-1)), Pb (18790mgkg(-1)) and Zn (8500mgkg(-1)) concentrations in
      surface soils (0-10cm) are elevated above guideline values. Samples with high PHE
      concentrations (e.g. As >1000mgkg(-1); Pb >1500mgkg(-1)) exhibit a wide range of
      bioaccessibilities (5.40 - 92.20% in the gastric (G) phase and 10.00 - 55.80% in
      the gastric-intestinal (G-I) phase). Samples associated with lower
      bioaccessibilities typically contain a number of XRD-identifiable primary and
      secondary mineral phases, particularly As- and Pb-bearing arsenian pyrite,
      beudantite, galena and cerrusite. Quantification of the potential human exposure
      risk associated with the ingestion of soil-associated PHEs indicates that on
      average, 0.01MUg Cd kg(-1) BW d(-1), 0.16MUg Cu kg(-1) BW d(--1), 0.12MUg As kg(
      1) BW d(-1), 7.81MUg Pb kg(-1) BW d(-1), and 2.68MUg Zn kg(-1) BW d(-1) could be
      bioaccessible following ingestion of PHE-rich soils in the Mitrovica region, with
      Pb, and to a lesser extent As, indicating the likely possibility of local
      populations exceeding the recommended tolerable daily intake. Lead present within
      surface soils of the area could indeed have contributed to the human Pb burden
      due to the high bioaccessibility of Pb present within these soils (13.40 - 92.20%
      in the gastric phase). Data for Pb levels in scalp hair (<=120MUgg(-1)) and blood
      (>=650MUgdL(-1); WHO, 2004) for children that have lived within IDP camps in
      Mitrovica indicate significant Pb uptake has indeed taken place. The highly
      bioaccessible nature of soil-associated PHEs in this study highlights the need
      for appropriate environmental management approaches that limit the exposure of
      local populations to these contaminated soils. 

PMID- 24013021
TI  - A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human
      health effects.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds
      comprised of two or more fused benzene rings arranged in various configurations.
      PAHs are widespread environmental contaminants formed as a result of incomplete
      combustion of organic materials such as fossil fuels. The occurrence of PAHs in
      ambient air is an increasing concern because of their carcinogenicity and
      mutagenicity. Although emissions and allowable concentrations of PAHs in air are
      now regulated, the health risk posed by PAH exposure suggests a continuing need
      for their control through air quality management. In light of the environmental
      significance of PAH exposure, this review offers an overview of PAH properties,
      fates, transformations, human exposure, and health effects (acute and chronic)
      associated with their emission to the atmosphere. Biomarkers of PAH exposure and
      their significance are also discussed. 

PMID- 24013022
TI  - Temporal trends of perfluoroalkyl acids in plasma samples of pregnant women in
      Hokkaido, Japan, 2003-2011.
AB  - Perfluoroalkyl acids (PFAAs) are persistent organic pollutants that are used in a
      wide range of consumer products. Recent epidemiological studies have shown that
      prenatal exposure to toxic levels of PFAAs in the environment may adversely
      affect fetal growth and humoral immune response in infants and children. Here we
      have characterized levels of prenatal exposure to PFAA between 2003 and 2011 in
      Hokkaido, Japan, by measuring PFAA concentrations in plasma samples from pregnant
      women. The study population comprised 150 women who enrolled in a prospective
      birth cohort study conducted in Hokkaido. Eleven PFAAs were measured in maternal
      plasma samples using simultaneous analysis by ultra-performance liquid
      chromatography coupled to triple quadrupole tandem mass spectrometry. At the end
      of the study, in 2011, age- and parity-adjusted mean concentrations of
      perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic
      acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid
      (PFDoDA), perfluorotridecanoic acid (PFTrDA), perfluorohexane sulfonate (PFHxS),
      and perfluorooctane sulfonate (PFOS) were 1.35ng/mL, 1.26ng/mL, 0.66ng/mL,
      1.29ng/mL, 0.25ng/mL, 0.33ng/mL, 0.28ng/mL, and 3.86ng/mL, respectively. Whereas
      PFOS and PFOA concentrations declined 8.4%/y and 3.1%/y, respectively, PFNA and
      PFDA levels increased 4.7%/y and 2.4%/y, respectively, between 2003 and 2011.
      PFUnDA, PFDoDA, and PFTrDA were detected in the vast majority of maternal
      samples, but no significant temporal trend was apparent. Future studies must
      involve a larger population of pregnant women and their children to determine the
      effects of prenatal exposure to PFAA on health outcomes in infants and children. 

PMID- 24013024
TI  - Possible origins and evolution of the hepatitis B virus (HBV).
AB  - All members of the family Hepadnaviridae are primarily viruses which contain
      double-stranded DNA genomes that are replicated via reverse transcription of a
      pregenomic RNA template. There are two subgroups within this family: mammalian
      and avian. The avian member's include the duck hepatitis B virus (DHBV), heron
      hepatitis B virus, Ross goose hepatitis B virus, stork hepatitis B virus and the
      recently identified parrot hepatitis B virus. More recently, the detection of
      endogenous avian hepadnavirus DNA integrated into the genomes of zebra finches
      has revealed a deep evolutionary origin of hepadnaviruses that was not previously
      recognised, dating back over 40 million years ago. The non-primate mammalian
      members of the Hepadnaviridae include the woodchuck hepatitis virus (WHV), the
      ground squirrel hepatitis virus and arctic squirrel virus, as well as the
      recently described bat hepatitis virus. The identification of hepatitis B virus
      (HBV) in higher primates such as chimpanzee, gorilla, orangutan, and gibbons that
      cluster with the human genotypes further implies a more complex origin of this
      virus. By studying the molecular epidemiology of HBV in indigenous and relict
      populations in Asia-Pacific we propose a model for the origin and evolution of
      HBV that involves multiple cross-species transmissions and subsequent
      recombination events on a background of genotype C HBV infection. 

PMID- 24013023
TI  - A review of the current understanding and clinical utility of miRNAs in
      esophageal cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) are a class of small, well-conserved, non-coding
      RNAs that regulate the translation of RNAs. They have a role in biological and
      pathological process including cell differentiation, apoptosis, proliferation and
      metabolism. Since their discovery, they have been shown to have a potential role
      in cancer pathogenesis through their function as oncogenes or tumor suppressors.
      A substantial number of miRNAs show differential expression in esophageal cancer
      tissues, and so have been investigated for possible use in diagnosis.
      Furthermore, there is increasing interest in their use as prognostic markers and
      determining treatment response, as well as identifying their downstream targets
      and understanding their mode of action. METHODS: We analyzed the most recent
      studies on miRNAs in esophageal cancer and/or Barrett's esophagus (BE). The
      publications were identified by searching in PuBMed for the following terms:
      Barrett's esophagus and microRNA; esophageal cancer and microRNA. RESULTS: Four
      miRNAs (mi-R-25, -99a, -133a and -133b) showed good potential as diagnostic
      markers and interestingly five (mi-R-21, -27b, -126, - 143 and -145) appeared to
      be useful both as diagnostic and prognostic/predictive markers. CONCLUSION: The
      data so far on miRNAs in esophageal carcinogenesis is promising but further work
      is required to determine whether miRNAs can be used as biomarkers, not only in
      the clinical setting or added to individualized treatment regimes but also in non
      invasive test by making use of miRNAs identified in blood.

PMID- 24013025
TI  - Effect of sterilization on structural and material properties of 3-D silk fibroin
      scaffolds.
AB  - The development of porous scaffolds for tissue engineering applications requires
      the careful choice of properties, as these influence cell adhesion, proliferation
      and differentiation. Sterilization of scaffolds is a prerequisite for in vitro
      culture as well as for subsequent in vivo implantation. The variety of methods
      used to provide sterility is as diverse as the possible effects they can have on
      the structural and material properties of the three-dimensional (3-D) porous
      structure, especially in polymeric or proteinous scaffold materials. Silk fibroin
      (SF) has previously been demonstrated to offer exceptional benefits over
      conventional synthetic and natural biomaterials in generating scaffolds for
      tissue replacements. This study sought to determine the effect of sterilization
      methods, such as autoclaving, heat-, ethylene oxide-, ethanol- or antibiotic
      antimycotic treatment, on porous 3-D SF scaffolds. In terms of scaffold
      morphology, topography, crystallinity and short-term cell viability, the
      different sterilization methods showed only few effects. Nevertheless, mechanical
      properties were significantly decreased by a factor of two by all methods except
      for dry autoclaving, which seemed not to affect mechanical properties compared to
      the native control group. These data suggest that SF scaffolds are in general
      highly resistant to various sterilization treatments. Nevertheless, care should
      be taken if initial mechanical properties are of interest. 

PMID- 24013026
TI  - C57BL/6 NK cell gene complex is crucially involved in vascular remodeling.
AB  - OBJECTIVE: NK cells are known to be involved in cardiovascular disease processes.
      One of these processes, vascular remodeling, may strongly differ between
      individuals and mouse strains such as the C57BL/6 and BALB/c. Moreover, C57BL/6
      and BALB/c mice vary in immune responses and in the composition of their Natural
      Killer gene Complex (NKC). Here we study the role of NK cells, and in particular
      the C57BL/6 NKC in vascular remodeling and intimal hyperplasia formation. METHODS
      AND RESULTS: C57BL/6, BALB/c and CMV1(r) mice, a BALB/c strain congenic for the
      C57BL/6 NKC, were used in an injury induced cuff model and a vein graft model. NK
      cell depleted C57BL/6 mice demonstrated a 43% reduction in intimal hyperplasia
      after femoral artery cuff placement compared to control C57BL/6 mice (p<0.05).
      Cuff placement and vein grafting resulted in profound intimal hyperplasia in
      C57BL/6 mice, but also in CMV1(r) mice, whereas this was significantly less in
      BALB/c mice. Significant more leukocyte infiltrations and IFN-gamma staining were
      seen in both C57BL/6 and CMV1(r) vein grafts compared to BALB/c vein grafts.
      CONCLUSIONS: These data demonstrate an important role for NK cells in intimal
      hyperplasia and vascular remodeling. Furthermore, the C57BL/6 NKC in CMV1(r) mice
      stimulates vascular remodeling most likely through the activation of (IFN-gamma
      secreting) NK-cells that modulate the outcome of vascular remodeling.

PMID- 24013027
TI  - Serotonin directly stimulates cortisol secretion from the interrenals in
      goldfish.
AB  - While serotonin (5-HT) can stimulate the hypothalamic-pituitary-interrenal stress
      axis in fish, the specific site(s) of 5-HT action are poorly understood. In this
      study, goldfish (Carassius auratus) were injected intraperitoneally with either
      saline or the 5-HT1A/7 receptor agonist 8-OH-DPAT at a dose of 100 or 400 MUg/kg
      body weight and sampled 1.5 and 8 h post-injection. Relative to unhandled
      controls, the saline and 100 MUg/kg 8-OH-DPAT treatments elicited similar
      transient 5- to 7-fold increases in plasma cortisol and the 400 MUg/kg 8-OH-DPAT
      dosage resulted in a sustained 16-fold increase in cortisol levels. Although the
      5-HT1A receptor is expressed in the brain preoptic area (POA), the pituitary and
      the head kidney, neither the saline nor the 8-OH-DPAT treatments affected the
      mRNA abundance of POA corticotropin-releasing factor and pituitary pro
      opiomelanocortin or plasma adrenocorticotropic hormone (ACTH) levels. To assess
      the direct actions of 5-HT on cortisol secretion relative to those of ACTH, head
      kidney tissue were superfused with 10(-7)M 5-HT, ACTH or a combined 5-HT/ACTH
      treatment. Overall, the ACTH and 5-HT/ACTH treatments resulted in higher peak
      cortisol and total cortisol release than in the 5-HT treatment but the response
      time to peak cortisol release was shorter in the combined treatment than in
      either the 5-HT or ACTH alone treatments. Both 8-OH-DPAT and cisapride, a 5-HT4
      receptor agonist, also stimulated cortisol release in vitro and their actions
      were reversed by selective 5-HT1A and 5-HT4 receptor antagonists, respectively.
      Finally, double-labeling with anti-tyrosine hydroxylase and anti-5-HT revealed
      that the chromaffin cells of the head kidney contain 5-HT. Thus, in goldfish, 5
      HT can directly stimulate cortisol secretion from the interrenals via multiple 5
      HT receptor subtypes and the chromaffin cells may be involved in the paracrine
      regulation of cortisol secretion via 5-HT.

PMID- 24013028
TI  - Mediation of glucose-induced anorexia by central nervous system interleukin 1
      signaling.
AB  - Hypothalamic glucose sensing plays a critical role in the regulation of food
      intake and metabolism. Glucose injection, either centrally or peripherally
      suppresses food intake. However, the mechanism of glucose-induced feeding
      suppression is not fully understood. It has been demonstrated that hypothalamic
      interleukin 1 beta (IL-1beta) mRNA levels are altered by metabolic states and IL
      1 signaling participates in the regulation of food intake. Therefore, we
      hypothesized that hypothalamic IL-1 gene expression is regulated by glucose and
      glucose-induced feeding suppression is mediated via hypothalamic IL-1 signaling.
      To address this hypothesis, we examined the effect of glucose on IL-1alpha and IL
      1beta mRNA expression in the hypothalamus. We also examined the effect of
      intraperitoneal injection of glucose on food intake in wild-type and type I IL-1
      receptor (IL-1RI)-deficient mice. Levels of IL-1alpha and IL-1beta mRNA in the
      hypothalamus were increased in response to feeding and intraperitoneal injection
      of glucose, and were positively correlated with blood glucose levels in mice.
      Exposure of hypothalamic explants to high glucose (10 mM) media increased IL
      1alpha and IL-1beta mRNA levels compared to low glucose (1 mM) media.
      Intraperitoneal glucose administration reduced food intake in wild-type mice,
      while the feeding-suppressing effect of glucose was attenuated in IL-1RI
      deficient mice. These findings support the role for hypothalamic IL-1 signaling
      in the mediation of the anorectic effect of glucose.

PMID- 24013029
TI  - Genistein stimulates fatty acid oxidation in a leptin receptor-independent manner
      through the JAK2-mediated phosphorylation and activation of AMPK in skeletal
      muscle.
AB  - Obesity is a public health problem that contributes to the development of insulin
      resistance, which is associated with an excessive accumulation of lipids in
      skeletal muscle tissue. There is evidence that soy protein can decrease the
      ectopic accumulation of lipids and improves insulin sensitivity; however, it is
      unknown whether soy isoflavones, particularly genistein, can stimulate fatty acid
      oxidation in the skeletal muscle. Thus, we studied the mechanism by which
      genistein stimulates fatty acid oxidation in the skeletal muscle. We showed that
      genistein induced the expression of genes of fatty acid oxidation in the skeletal
      muscle of Zucker fa/fa rats and in leptin receptor (ObR)-silenced C2C12 myotubes
      through AMPK phosphorylation. Furthermore, the genistein-mediated AMPK
      phosphorylation occurred via JAK2, which was possibly activated through a
      mechanism that involved cAMP. Additionally, the genistein-mediated induction of
      fatty acid oxidation genes involved PGC1alpha and PPARdelta. As a result, we
      observed that genistein increased fatty acid oxidation in both the control and
      silenced C2C12 myotubes, as well as a decrease in the RER in mice, suggesting
      that genistein can be used in strategies to decrease lipid accumulation in the
      skeletal muscle. 

PMID- 24013030
TI  - Preparation and characterization of a novel tobramycin-containing antibacterial
      collagen film for corneal tissue engineering.
AB  - Corneal disease is a major cause of blindness and keratoplasty is an effective
      treatment method. However, clinical treatment is limited due to a severe shortage
      of high-quality allogeneic corneal tissues and the bacterial infection after
      corneal transplantation. In this study, we develop a novel artificial and
      antibacterial collagen film (called Col-Tob) for corneal repair. In the Col-Tob
      film, the tobramycin, which is an aminoglycoside antibiotic to treat various
      types of bacterial infections, was cross-linked by 1-ethyl-3-(3-dimethyl
      aminopropyl) carbodiimide and N-hydroxysuccinimide onto the collagen. Physical
      properties, antibacterial property and biocompatibility of the films were
      characterized. The results indicate that the film is basically transparent and
      has appropriate mechanical properties. Cell experiments show that human corneal
      epithelial cells could adhere to and proliferate well on the film. Most
      importantly, the film exhibits excellent antibacterial effect in vitro. Lamellar
      keratoplasty shows that the Col-Tob film can be sutured in rabbit eyes and are
      epithelialized completely in 15 +/- 5 days, and their transparency is restored
      quickly in the first month. Corneal rejection reaction, neovascularization and
      keratoconus are not observed within 3 months. This film, which can be prepared in
      large quantities and at low cost,should have potential application in corneal
      repair.

PMID- 24013031
TI  - Combined HPLC-DAD-MS, HPLC-MS(n) and NMR spectroscopy for quality control of
      plant extracts: the case of a commercial blend sold as dietary supplement.
AB  - The efficiency of 1D and 2D NMR spectroscopy along with HPLC-DAD-MS analyses in
      characterising the content of a dietary supplement is demonstrated. Experiments
      directly performed on a lyophilised sample of a commercial product gave details
      on the quality control of the product. The lack of the marker constituents of
      some of the declared plant species (Crataegus oxyacantha, Olea europea, Capsella
      bursa-pastoris and Fumaria officinalis) and the presence of banned adulterants,
      responsible for the strong antihypertensive effect of the supplement were
      established. The analyses proved the presence of indole alkaloids belonging to
      the group of Rauwolfia sp., such as ajmaline, reserpine and yohimbine.
      Quantitative HPLC analysis showed that the content of reserpine in the product
      was in the therapeutic range and therefore responsible for the collapses of the
      patients. 

PMID- 24013032
TI  - Pharmacokinetic study of ginsenoside Rc and simultaneous determination of its
      metabolites in rats using RRLC-Q-TOF-MS.
AB  - A rapid resolution liquid chromatography coupled with quadruple-time-of-flight
      mass spectrometry (RRLC-Q-TOF-MS) method was developed for pharmacokinetic study
      of ginsenoside Rc and applied in the simultaneous determination of ginsenoside Rc
      metabolites in rats. The experimental results indicate that the concentration
      versus time profile of ginsenoside Rc shows a two-compartment pharmacokinetic
      model after intravenous administration of ginsenoside Rc at a dosage of 0.4mg/kg
      for rats. In the metabolic study, prototype ginsenoside Rc and its deglycosylated
      metabolites Mb, Mc, and compound K were characterized by comparing the retention
      time (tR), accurate mass, and characteristic MS/MS fragment ions with standard
      compounds. The experiments show that part of the ginsenoside Rc was excreted
      through urine as prototype and part was metabolized into metabolites Mb and Mc
      after intravenous administration. In contrast, most of ginsenoside Rc were
      transformed into Mc and CK in feces after oral administration. The in vivo
      metabolic pathway of ginsenoside Rc was summarized. 

PMID- 24013033
TI  - A comparison of methods for classifying samples as truly specific with
      confirmatory immunoassays.
AB  - Biotechnology-derived therapeutics may induce an unwanted immune response leading
      to the formation of anti-drug antibodies (ADAs) which can result in altered
      efficacy and safety of the therapeutic protein. Anti-drug antibodies may, for
      example, affect pharmacokinetics of the therapeutic protein or induce
      autoimmunity. It is therefore crucial to have assays available for the detection
      and characterization of ADAs. Commonly, a screening assay is initially used to
      classify samples as either ADA positive or negative. A confirmatory assay,
      typically based on antigen competition, is subsequently employed to separate
      false positive samples from truly positive samples. In this manuscript we
      investigate the performance of different statistical methods classifying samples
      in competition assays through simulation and analysis of real data. In our
      evaluations we do not find a uniformly best method although a simple t-test does
      provide good results throughout. More crucially we find that very large
      differences between uninhibited and inhibited measurements relative to the assay
      variability are required in order to obtain useful classification results
      questioning the usefulness of competition assays with high variability. 

PMID- 24013035
TI  - A multi-target, non-infectious and clonable artificial positive control for
      routine PCR-based assays.
AB  - Positive controls are essential for PCR reliability and are challenging to obtain
      for rare, exotic and/or emerging pathogens and pose biosafety risks if
      manufactured using infectious pathogens. Custom synthetic DNA inserts can be
      designed de novo in tandems of forward and reverse complement priming sequences
      to be inserted in circular plasmid vectors. To test this concept, artificial
      positive controls (APCs) for use in PCR were synthesized to contain primer
      sequences targeting four viruses (Barley yellow dwarf virus, Soilborne wheat
      mosaic virus, Triticum mosaic virus and Wheat streak mosaic virus) pathogenic to
      wheat and, as internal control, the plant mitochondrial nad5 gene. Thermodynamics
      and folding parameters of twenty-four APC inserts were assessed in silico. Two
      thermodynamically different APCs, designated optimal and sub-optimal, were cloned
      and tested using end point PCR. The optimal APC had a 100% amplification rate,
      while only 92% of virus-infected plant tissues, commonly used as reference
      positive controls, amplified. An array of APC priming sequences from different
      organisms and/or previously tested primers can be accommodated in a large and
      flexible number of positive control targets. APCs will streamline and standardize
      routine PCR, improve reliability and biosafety, and create opportunities for
      development and commercialization of new synthetic positive control sequences. 

PMID- 24013034
TI  - Impact of pubertal and adult estradiol treatments on cocaine self-administration.
AB  - Estradiol is thought to play a critical role in the increased vulnerability to
      psychostimulant abuse in women. Sex differences in the ability of estradiol to
      influence cocaine self-administration in adult rats have been hypothesized to
      depend upon pubertal estradiol exposure. The current study investigated whether
      the presence of gonadal hormones during puberty affected cocaine self
      administration behavior and its sensitivity to adult estradiol treatment in male
      and female Sprague-Dawley rats. Subjects were gonadectomized or SHAM-operated at
      postnatal day (PD) 22, and received either OIL or estradiol benzoate (EB) during
      the approximate time of puberty (PD27 to PD37). Adult rats were subsequently
      treated with either EB or OIL 30 min before cocaine self-administration (0.3
      mg/kg/inf) in order to examine the effects of pubertal manipulations on the
      estradiol sensitivity of acquisition on a fixed ratio (FR) 1 schedule, total
      intake on a FR5 schedule and motivation on a progressive ratio schedule. Adult EB
      treatment only affected cocaine self-administration in females, which is
      consistent with previous research. Adult EB treatment enhanced acquisition in all
      females irrespective of puberty manipulations. All females, except those treated
      with EB during puberty, displayed increased cocaine intake following adult EB
      treatment. Adult EB treatment only enhanced motivation in females that were
      intact during puberty, whereas those treated with EB during puberty showed
      reduced motivation. Therefore, the sensitivities of different self-administration
      behaviors to adult estradiol treatment are organized independently in females,
      with pubertal estradiol exerting a greater influence over motivational processes,
      and negligible effects on learning/acquisition.

PMID- 24013036
TI  - Norbisabolane and eremophilane sesquiterpenoids from cultures of the
      Basidiomycete Polyporus ellisii.
AB  - Three new 11,12,15-norbisabolane sesquiterpenoids, polisins A-C (1-3), and four
      new eremophilane sesquiterpenoids, polylisins A-D (4-7), were isolated from
      cultures of the Basidiomycete Polyporus ellisii. These new structures were
      elucidated based on extensive spectroscopic studies and the structures of polisin
      A (1) and polylisin A (4) were confirmed by single-crystal X-ray crystallographic
      analysis. All compounds were evaluated for their inhibitory activities against
      two isozymes of 11beta-hydroxysteroid dehydrogenases (11beta-HSD1 and 11beta
      HSD2). 

PMID- 24013037
TI  - Antinociceptive activity of cyclopeptide alkaloids isolated from Ziziphus
      oxyphylla Edgew (Rhamnaceae).
AB  - The current study was designed to evaluate the antinociceptive profile of five
      cyclopeptide alkaloids isolated from Ziziphus oxyphylla, including Oxyphylline-B
      1, Oxyphylline C 2 Oxyphylline-D 3, Nummularin-C 4, and Nummularin-R 5. The
      effect was studied in acetic acid induced writhing and formalin induced flinching
      behavior tests, at 2.5 and 5mg/kg i.p. In the post-acetic acid induced writhing
      test, the compounds significantly ameliorated abdominal constrictions in a dose
      dependent manner, with compounds 1 and 5 showing 80.98% and 77.87% protection,
      respectively. When challenged in the formalin induced test, pretreatment of
      compounds significantly attenuated painful sensation in both phases. Moreover,
      compounds 1 and 5 were more effective with 45.32% and 75.32% for 1 and 36.77% and
      71.10% protection for 5, in the 1st and 2nd phases respectively. The peripheral
      analgesia was strongly augmented by the central effects of these compounds. The
      current finding strongly supports the ethnomedicinal use of this valuable
      medicinal plant in various painful conditions. 

PMID- 24013038
TI  - The effect of reducing the number of cigarettes smoked on risk of lung cancer,
      COPD, cardiovascular disease and FEV(1)--a review.
AB  - Searches identified 14 studies investigating effects of reducing cigarette
      consumption on lung cancer, CVD, COPD or FEV1 decline. Three were case-control
      studies, six cohort studies, and five follow-up studies of FEV1. Six studies
      consistently reported lower lung cancer risk in reducers. Compared to non
      reducers, meta-analysis (random-effects) showed significantly lower risk (RR
      0.81, 95% CI 0.74-0.88 for any reduction, and RR 0.78, 0.66-0.92 for the greatest
      reduction), with no between-study heterogeneity. Four cohort studies presented
      CVD results, the combined RR for any reduction being a non-significant 0.93 (0.84
      1.03). An effect of reduction was not consistently seen for COPD or FEV1 decline.
      Four cohort studies presented all-cause mortality results, the combined RR of
      0.92 (0.85-1.01) being non-significant. The RR of 0.95 (0.88-1.02) for total
      smoking-related cancer, from three studies, was also non-significant. The
      evidence has various weaknesses; few studies, few cases in reducers in some
      studies, limited dose-response data, incomplete adjustment for baseline
      consumption, questionable accuracy of the lifetime smoking history data in case
      control studies, and bias in cohort studies if reducers are likelier than non
      reducers to quit during follow-up. Also, the variable definitions of reduction
      make meta-analysis problematic. Though the results suggest some benefits of
      smoking reduction, more evidence is needed. 

PMID- 24013040
TI  - Signaling stress? An analysis of phaeomelanin-based plumage color and individual
      corticosterone levels at two temporal scales in North American barn swallows,
      Hirundo rustica erythrogaster.
AB  - Sexually selected traits confer greater reproductive benefits to individuals with
      more elaborate forms of the signal. However, whether these signals convey
      reliable information about the physiology underlying trait development remains
      unknown in many species. The steroid hormone corticosterone (CORT) mediates
      important physiological and behavioral processes during the vertebrate stress
      response, and CORT secretion itself can be modulated by melanocortins. Thus,
      sexually selected melanin-based plumage coloration could function as an honest
      signal of an individual's ability to respond to stressors. This hypothesis was
      tested in North American barn swallows, Hirundo rustica erythrogaster, where
      males with darker ventral plumage color exhibit higher phaeomelanin content and
      are more successful at reproduction. Because reproductive behavior occurs months
      after plumage signals are developed, we also addressed the potential temporal
      disconnect of physiological state during trait development and trait
      advertisement by analyzing three different measurements of CORT levels in adult
      males during the breeding season (trait advertisement) and in nestling males
      while they were growing their feathers (trait development). Variation in adult
      plumage color did not predict baseline or stress-induced CORT, or stress
      responsiveness. Likewise, there was no relationship between nestling plumage
      color and any of the CORT measurements, but heavier nestlings had significantly
      lower baseline CORT. Our finding that a predominantly phaeomelanin-based trait is
      unrelated to circulating CORT suggests that phaeomelanin and eumelanin signals
      may convey different physiological information, and highlights the need for
      further study on the biochemical links between the hypothalamic-pituitary-adrenal
      (HPA) axis and the production of different melanin-based pigments. 

PMID- 24013041
TI  - Rapidly progressive multifocal phyllodes tumour of the breast: A case report and
      review of the literature.
AB  - INTRODUCTION: Malignant transformation of a phyllodes tumour is a rare form of
      breast cancer, accounting for just 0.5% of all breast cancer cases.(1)
      PRESENTATION OF CASE: We report a case of a 49 year old female with rapidly
      progressive, multifocal disease. She initially presented with two giant
      fibroadenomas which were excised. She represented eight months post surgery with
      two new lesions in the same breast, one suspicious, one suggestive of
      fibroadenoma. Biopsy was borderline. Surgery was therefore scheduled for wide
      local excision. At localisation two weeks later, at least eight lesions were seen
      on ultrasound scan. Three were removed as histology was at this point unknown to
      conserve the breast. Histology revealed intermediate grade DCIS, benign Phyllodes
      and borderline/malignant phyllodes. She was scheduled for mastectomy and
      immediate Strattice reconstruction. An MRI was performed pre-operatively to
      ascertain extent of disease. Two weeks post localisation, 13 lesions were
      identified. The right breast was entirely unaffected. Surgery interval was three
      weeks and final histology revealed 18 lesions, ranging from fibroadenoma through
      to borderline/malignant phyllodes with an incidental papilloma. DISCUSSION: This
      is the first report of such rapid progression of disease, with 16 new lesions, of
      varied histology, developing in just an eight week period. CONCLUSION: This case
      highlights the difficulty of forming a clear diagnostic and therapeutic pathway
      in this highly variable disease. Arguments for over and under treating these
      patients remain but those with any borderline/malignant potential have to be
      removed as recurrence is both common and aggressive, with a clear surgical margin
      the only proven protective factor.

PMID- 24013039
TI  - Voluntary exercise impairs initial delayed spatial alternation performance in
      estradiol treated ovariectomized middle-aged rats.
AB  - Estrogens differentially modulate behavior in the adult female rodent. Voluntary
      exercise can also impact behavior, often reversing age associated decrements in
      memory processes. Our research group has published a series of papers reporting a
      deficit in the acquisition of an operant working memory task, delayed spatial
      alternation (DSA), following 17beta-estradiol treatment to middle-aged
      ovariectomized (OVX) rats. The current study examined if voluntary exercise could
      attenuate the 17beta-estradiol induced deficits on DSA performance. OVX 12-month
      old Long-Evans rats were implanted with a Silastic capsule containing 17beta
      estradiol (10% in cholesterol: low physiological range) or with a blank capsule.
      A subset of the 17beta-estradiol and OVX untreated rats were given free access to
      a running wheel in their home cage. All rats were tested for 40 sessions on the
      DSA task. Surprisingly, we found running wheel access to impair initial
      acquisition of the DSA task in 17beta-estradiol treated rats, an effect not seen
      in OVX untreated rats given running wheel access. This deficit was driven by an
      increase in perseverative responding on a lever no longer associated with
      reinforcement. We also report for the first time a 17beta-estradiol induced
      impairment on the DSA task following a long intertrial delay (18-sec), an effect
      revealed following more extended testing than in our previous studies (15
      additional sessions). Overall, running wheel access increased initial error rate
      on the DSA task in 17beta-estradiol treated middle-aged OVX rats, and failed to
      prevent the 17beta-estradiol induced deficits in performance of the operant DSA
      task in later testing sessions. 

PMID- 24013042
TI  - Longitudinal, quantitative monitoring of therapeutic response in 3D in vitro
      tumor models with OCT for high-content therapeutic screening.
AB  - In vitro three-dimensional models of cancer have the ability to recapitulate many
      features of tumors found in vivo, including cell-cell and cell-matrix
      interactions, microenvironments that become hypoxic and acidic, and other
      barriers to effective therapy. These model tumors can be large, highly complex,
      heterogeneous, and undergo time-dependent growth and treatment response processes
      that are difficult to track and quantify using standard imaging tools. Optical
      coherence tomography is an optical ranging technique that is ideally suited for
      visualizing, monitoring, and quantifying the growth and treatment response
      dynamics occurring in these informative model systems. By optimizing both optical
      coherence tomography and 3D culture systems, it is possible to continuously and
      non-perturbatively monitor advanced in vitro models without the use of labels
      over the course of hours and days. In this chapter, we describe approaches and
      methods for creating and carrying out quantitative therapeutic screens with in
      vitro 3D cultures using optical coherence tomography to gain insights into
      therapeutic mechanisms and build more effective treatment regimens. 

PMID- 24013044
TI  - Reply: Diagnosis of "paradoxical" low-gradient aortic stenosis patients.

PMID- 24013043
TI  - Metabolic imaging in multiple time scales.
AB  - We report here a novel combination of time-resolved imaging methods for probing
      mitochondrial metabolism in multiple time scales at the level of single cells. By
      exploiting a mitochondrial membrane potential reporter fluorescence we
      demonstrate the single cell metabolic dynamics in time scales ranging from
      microseconds to seconds to minutes in response to glucose metabolism and
      mitochondrial perturbations in real time. Our results show that in comparison
      with normal human mammary epithelial cells, the breast cancer cells display
      significant alterations in metabolic responses at all measured time scales by
      single cell kinetics, fluorescence recovery after photobleaching and by scaling
      analysis of time-series data obtained from mitochondrial fluorescence
      fluctuations. Furthermore scaling analysis of time-series data in living cells
      with distinct mitochondrial dysfunction also revealed significant metabolic
      differences thereby suggesting the broader applicability (e.g. in mitochondrial
      myopathies and other metabolic disorders) of the proposed strategies beyond the
      scope of cancer metabolism. We discuss the scope of these findings in the context
      of developing portable, real-time metabolic measurement systems that can find
      applications in preclinical and clinical diagnostics. 

PMID- 24013045
TI  - Resection of left ventricular rhabdomyosarcoma.

PMID- 24013046
TI  - Reply: left ventricular assist devices in chronic heart failure: more questions
      than answers?

PMID- 24013047
TI  - Reply: Enalapril and carvedilol for preventing chemotherapy-induced left
      ventricular systolic dysfunction in patients with malignant hemopathies.

PMID- 24013048
TI  - Enalapril and carvedilol for preventing chemotherapy-induced left ventricular
      systolic dysfunction.

PMID- 24013049
TI  - Enalapril/carvedilol for prevention of chemotherapy-induced heart failure: an end
      to the problem.

PMID- 24013050
TI  - Left ventricular assist devices in chronic heart failure: more questions than
      answers?

PMID- 24013051
TI  - Insulin as a biomarker to predict vascular protection from weight-loss therapy.

PMID- 24013052
TI  - Why are clinically indicated, but lower-risk, patients less likely to receive
      implantable cardioverter-defibrillator and cardiac resynchronization therapy?

PMID- 24013053
TI  - New insights into ventricular interactions during cardiac resynchronization.

PMID- 24013054
TI  - Carotid body denervation: too soon to get breathless about heart failure?

PMID- 24013055
TI  - The relationship between pre-eclampsia and peripartum cardiomyopathy: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: The goal of this study was to systematically review the peripartum
      cardiomyopathy (PPCM) literature and determine the prevalence of pre-eclampsia
      (PE) in women with PPCM. Secondary analyses included evaluation of the prevalence
      of hypertensive disorders, multiple gestations, and multiparity. BACKGROUND: PPCM
      is a significant cause of maternal and infant morbidity and mortality worldwide,
      yet its etiology remains unknown. PE is often cited as a risk factor for the
      development of PPCM and recent research suggests that PE and PPCM share
      mechanisms that contribute to their pathobiology. No comprehensive evaluation of
      the relationship between PE and PPCM exists. METHODS: A systematic predetermined
      search strategy was performed in multiple databases to identify studies
      describing >=3 women with PPCM. Prevalence rates of PE, hypertension, multiple
      gestations, and multiparity were pooled. RESULTS: Data from 22 studies (n = 979)
      were included in this analysis. The pooled prevalence of 22% (95% confidence
      interval [CI]: 16% to 28%) was more than quadruple the 5% average worldwide
      background rate of PE in pregnancy (p < 0.001). There were no geographic or
      racial differences detected in the prevalence of PE in women with PPCM. The rates
      of hypertension during pregnancy (37% [95% CI: 29% to 45%]) and multiple
      gestations (9% [95% CI: 7% to 11%]) were also elevated. CONCLUSIONS: The
      prevalence of PE, hypertensive disorders, and multiple gestations in women with
      PPCM is markedly higher than that in the general population. These findings
      support the concept of a shared pathogenesis between PE and PPCM and highlight
      the need for awareness of the overlap between these 2 diseases.

PMID- 24013056
TI  - Carotid chemoreceptor ablation improves survival in heart failure: rescuing
      autonomic control of cardiorespiratory function.
AB  - OBJECTIVES: This study sought to investigate whether selective ablation of the
      carotid body (CB) chemoreceptors improves cardiorespiratory control and survival
      during heart failure. BACKGROUND: Chronic heart failure (CHF) is a recognized
      health problem worldwide, and novel treatments are needed to better improve life
      quality and decrease mortality. Enhanced carotid chemoreflex drive from the CB is
      thought to contribute significantly to autonomic dysfunction, abnormal breathing
      patterns, and increased mortality in heart failure. METHODS: Chronic heart
      failure was induced by coronary ligation in rats. Selective CB denervation was
      performed to remove carotid chemoreflex drive in the CHF state (16 weeks post
      myocardial infarction). Indexes of autonomic and respiratory function were
      assessed in CB intact and CB denervated animals. CB denervation at 2 weeks post
      myocardial infarction was performed to evaluate whether early targeted CB
      ablation decreases the progression of left ventricular dysfunction, cardiac
      remodeling, and arrhythmic episodes and improves survival. RESULTS: The CHF rats
      developed increased CB chemoreflex drive and chronic central pre-sympathetic
      neuronal activation, increased indexes of elevated sympathetic outflow, increased
      breathing variability and apnea incidence, and desensitization of the baroreflex.
      Selective CB ablation reduced the central pre-sympathetic neuronal activation by
      40%, normalized indexes of sympathetic outflow and baroreflex sensitivity, and
      reduced the incidence of apneas in CHF animals from 16.8 +/- 1.8 events/h to 8.0
      +/- 1.4 events/h. Remarkably, when CB ablation was performed early, cardiac
      remodeling, deterioration of left ventricle ejection fraction, and cardiac
      arrhythmias were reduced. Most importantly, the rats that underwent early CB
      ablation exhibited an 85% survival rate compared with 45% survival in CHF rats
      without the intervention. CONCLUSIONS: Carotid chemoreceptors play a seminal role
      in the pathogenesis of heart failure, and their targeted ablation might be of
      therapeutic value to reduce cardiorespiratory dysfunction and improve survival
      during CHF.

PMID- 24013057
TI  - Comparative electromechanical and hemodynamic effects of left ventricular and
      biventricular pacing in dyssynchronous heart failure: electrical
      resynchronization versus left-right ventricular interaction.
AB  - OBJECTIVES: The purpose of this study was to enhance understanding of the working
      mechanism of cardiac resynchronization therapy by comparing animal experimental,
      clinical, and computational data on the hemodynamic and electromechanical
      consequences of left ventricular pacing (LVP) and biventricular pacing (BiVP).
      BACKGROUND: It is unclear why LVP and BiVP have comparative positive effects on
      hemodynamic function of patients with dyssynchronous heart failure. METHODS:
      Hemodynamic response to LVP and BiVP (% change in maximal rate of left
      ventricular pressure rise [LVdP/dtmax]) was measured in 6 dogs and 24 patients
      with heart failure and left bundle branch block followed by computer simulations
      of local myofiber mechanics during LVP and BiVP in the failing heart with left
      bundle branch block. Pacing-induced changes of electrical activation were
      measured in dogs using contact mapping and in patients using a noninvasive
      multielectrode electrocardiographic mapping technique. RESULTS: LVP and BiVP
      similarly increased LVdP/dtmax in dogs and in patients, but only BiVP
      significantly decreased electrical dyssynchrony. In the simulations, LVP and BiVP
      increased total ventricular myofiber work to the same extent. While the LVP
      induced increase was entirely due to enhanced right ventricular (RV) myofiber
      work, the BiVP-induced increase was due to enhanced myofiber work of both the
      left ventricle (LV) and RV. Overall, LVdP/dtmax correlated better with total
      ventricular myofiber work than with LV or RV myofiber work alone. CONCLUSIONS:
      Animal experimental, clinical, and computational data support the similarity of
      hemodynamic response to LVP and BiVP, despite differences in electrical
      dyssynchrony. The simulations provide the novel insight that, through ventricular
      interaction, the RV myocardium importantly contributes to the improvement in LV
      pump function induced by cardiac resynchronization therapy.

PMID- 24013058
TI  - Mipomersen, an apolipoprotein B synthesis inhibitor, reduces atherogenic
      lipoproteins in patients with severe hypercholesterolemia at high cardiovascular
      risk: a randomized, double-blind, placebo-controlled trial.
AB  - OBJECTIVES: This study sought to examine the efficacy and safety of mipomersen
      for reducing atherogenic lipids and lipoproteins in patients with
      hypercholesterolemia. BACKGROUND: Many patients on lipid-lowering therapies
      remain unable to achieve target low-density lipoprotein (LDL) cholesterol levels.
      Mipomersen, an antisense oligonucleotide inhibitor of apolipoprotein B, reduces
      LDL cholesterol and atherogenic lipoproteins. METHODS: This randomized, double
      blind, multicenter study enrolled 158 patients with baseline LDL cholesterol
      levels >=100 mg/dl with, or at high risk for, coronary heart disease who were
      receiving maximally tolerated lipid-lowering therapy. Patients received weekly
      subcutaneous mipomersen 200 mg (n = 105) or placebo (n = 52) for 26 weeks, with a
      24-week follow-up period. Randomization was stratified by type 2 diabetes status.
      RESULTS: Sixty mipomersen and 44 placebo patients completed treatment. Mean
      baseline LDL cholesterol levels were 122.7 and 122.6 mg/dl in the placebo and
      mipomersen patients, respectively. Mipomersen reduced LDL cholesterol by -36.9%
      compared with placebo at -4.5% (p < 0.001). Target LDL cholesterol <100 mg/dl was
      attained in 76% of mipomersen and 38% of placebo patients. Mipomersen also
      significantly reduced apolipoprotein B (-38%) and lipoprotein(a) (-24%) (p <
      0.001). Common adverse events included injection site reactions (78% with
      mipomersen, 31% with placebo) and flu-like symptoms (34% with mipomersen, 21%
      with placebo). Elevations in transaminases and liver fat also occurred in some
      patients, and these levels returned toward baseline after treatment cessation.
      CONCLUSIONS: Mipomersen significantly reduced LDL cholesterol, apolipoprotein B,
      and lipoprotein(a) in patients with hypercholesterolemia with, or at risk for,
      coronary heart disease not controlled by existing therapies. (Safety and Efficacy
      of Mipomersen [ISIS 301012] as Add-On Therapy in High Risk Hypercholesterolemic
      Patients; NCT00770146).

PMID- 24013059
TI  - Echocardiographic and clinical outcomes of central versus noncentral percutaneous
      edge-to-edge repair of degenerative mitral regurgitation.
AB  - OBJECTIVES: This study aimed to assess the clinical and echocardiographic results
      of MitraClip implantation in noncentral degenerative mitral regurgitation (dMR)
      compared with central dMR. BACKGROUND: It is unknown whether the use of MitraClip
      therapy in noncentral dMR is as safe and effective as in central dMR. METHODS: We
      analyzed a multicenter registry of 173 patients treated with the MitraClip and
      compared results of central and noncentral dMR. RESULTS: Seventy-nine patients
      (age 79.2 +/- 8.0 years, 58.2% men) had dMR. Forty-nine patients (62%) had
      central dMR, with the remainder classified as noncentral dMR (n = 30, 38%).
      Patients with noncentral dMR had a wider pre-procedural vena contracta (8.5 +/-
      2.0 mm vs. 6.9 +/- 2.2 mm, p = 0.039) and higher systolic pulmonary pressure
      (57.9 +/- 18.0 vs. 47.3 +/- 13.0 mm Hg, p = 0.019). Procedural success was the
      same in both groups (95.5% central vs. 96.7% noncentral, p = 0.866). Post
      procedural MR and New York Heart Association (NYHA) functional class at 1 month
      (MR <=2, 96.0% vs. 96.6%, p = 0.866, and NYHA functional class <=II, 81.6% vs.
      90.0%, p = 0.335) and 6 months (95.2% central vs. 91.7% noncentral, p = 0.679;
      and NYHA functional class >II, 21.1% vs. 0%, p = 0.128) did not differ between
      groups. There were also no differences in serious post-procedural adverse events:
      partial clip detachment (central n = 1 [2.0%] vs. noncentral n = 1 [3.3%], p =
      1.000), death (5.4% central vs. 13.0% noncentral, p = 0.298), or heart failure
      admission (10.8% central vs. 8.7% noncentral, p = 0.791). CONCLUSIONS: In
      experienced centers, MitraClip treatment can be performed safely and effectively
      in both central and noncentral dMR.

PMID- 24013060
TI  - Noncentral mitral regurgitation: a new niche for the MitraClip.

PMID- 24013061
TI  - Lipid control in the modern era: an orphan's tale of rags to riches.

PMID- 24013062
TI  - Diagnosis of "paradoxical" low-gradient aortic stenosis patients.

PMID- 24013064
TI  - Structural effects on the hesperidin properties obtained by chelation to
      magnesium complexes.
AB  - The magnesium complex [Mg(hesp)2(phen)] (1), where hesp=hesperidin and phen=1,10'
      phenanthroline, was synthesized and characterized by Elemental Analysis (C,H,N),
      atomic absorption and spectroscopic (FTIR, UV-visible, (1)H NMR) techniques. The
      congested structure facilitates the tilting and contact of the two hesperidin
      ligands by hydrogen bonding interactions having a stabilizer effect on the
      hesperidin. The hydrogen bonds are strongly affected by the solvent used which
      can lead to changes in the physical-chemical, luminescence and biologic
      properties of complex 1. Complex 1 is more hydrosoluble (S=472+/-3.05MUgmL(-1))
      and liposoluble (log P=-0.15+/-0.01) than free hesperidin (S=5.92+/-0.49MUgmL(
      1), log P=0.30). Oxidation of the complex in an aqueous solution and room
      temperature investigated by cyclic voltammetry resulted in a very stable two
      electron cyclic process to form the phenoxonium neutral, cation and dication
      radicals. The stability of the voltammetric process indicates that the species
      produced are never exhausted and does not lead to changes in the coordination
      sphere composition. The complex was found to be a better radical scavenger for
      superoxide radical (IC50=68.3MUM at pH7.8) than free hesperidin
      (IC50=116.68MUmolL(-1)) and vitamin C (IC50=852MUmolL(-1)). The strong blue
      fluorescence of complex 1 switches through loss of luminescence in pure
      water/protic organic solvents or when protected from water (in octanol for
      example as a model of phospholipid membranes). These features provide an
      opportunity to map the reactivity of hesperidin in the physiologic medium. In
      this context, a high uptake of complex into HeLa cells was detected by
      fluorescence microscopy. The blue fluorescence was uniformly distributed mainly
      in per nucleic region. 

PMID- 24013063
TI  - Electrochemistry of mammalian cytochrome P450 2B4 indicates tunable thermodynamic
      parameters in surfactant films.
AB  - Electrochemical methods continue to present an attractive means for achieving in
      vitro biocatalysis with cytochromes P450; however understanding fully the nature
      of electrode-bound P450 remains elusive. Herein we report thermodynamic
      parameters using electrochemical analysis of full-length mammalian microsomal
      cytochrome P450 2B4 (CYP 2B4) in didodecyldimethylammonium bromide (DDAB)
      surfactant films. Electronic absorption spectra of CYP 2B4-DDAB films on silica
      slides reveal an absorption maximum at 418nm, characteristic of low-spin, six
      coordinate, water-ligated Fe(III) heme in P450. The Fe(III/II) and Fe(II/I) redox
      couples (E1/2) of substrate-free CYP 2B4 measured by cyclic voltammetry are 
      0.23V and -1.02V (vs. SCE, or 14mV and -776mV vs. NHE) at 21 degrees C. The
      standard heterogeneous rate constant for electron transfer from the electrode to
      the heme for the Fe(III/II) couple was estimated at 170s(-1). Experiments
      indicate that the system is capable of catalytic reduction of dioxygen, however
      substrate oxidation was not observed. From the variation of E1/2 with temperature
      (18-40 degrees C), we have measured entropy and enthalpy changes that accompany
      heme reduction, -151Jmol(-1)K(-1) and -46kJmol(-1), respectfully. The
      corresponding entropy and enthalpy values are less for the six-coordinate low
      spin, imidazole-ligated enzyme (-59Jmol(-1)K(-1) and -18kJmol(-1)), consistent
      with limited conformational changes upon reduction. These thermodynamic
      parameters are comparable to those measured for bacterial P450 from Bacillus
      megaterium (CYP BM3), confirming our prior reports that the surfactant
      environment exerts a strong influence on the redox properties of the heme. 

PMID- 24013065
TI  - Molecular and cell biological effects of 3,5,3'-triiodothyronine on progenitor
      cells of the enteric nervous system in vitro.
AB  - INTRODUCTION: Thyroid hormones play important roles in the development of neural
      cells in the central nervous system. Even minor changes to normal thyroid hormone
      levels affect dendritic and axonal outgrowth, sprouting and myelination and might
      even lead to irreversible damages such as cretinism. Despite our knowledge of the
      influence on the mammalian CNS, the role of thyroid hormones in the development
      of the enteric nervous system (ENS) still needs to be elucidated. In this study
      we have analyzed for the first time the influence of 3,5,3'-triiodothyronine (T3)
      on ENS progenitor cells using cell biological assays and a microarray technique.
      RESULTS: In our in vitro model, T3 inhibited cell proliferation and stimulated
      neurite outgrowth of differentiating ENS progenitor cells. Microarray analysis
      revealed a group of 338 genes that were regulated by T3 in differentiating
      enterospheres. 67 of these genes are involved in function and development of the
      nervous system. 14 of them belong to genes that are involved in axonal guidance
      or neurite outgrowth. Interestingly, T3 regulated the expression of netrin G1 and
      endothelin 3, two guidance molecules that are involved in human enteric
      dysganglionoses. CONCLUSION: The results of our study give first insights how T3
      may affect the enteric nervous system. T3 is involved in proliferation and
      differentiation processes in enterospheres. Microarray analysis revealed several
      interesting gene candidates that might be involved in the observed effects on
      enterosphere differentiation. Future studies need to be conducted to better
      understand the gene to gene interactions.

PMID- 24013066
TI  - Stepwise, non-adherent differentiation of human pluripotent stem cells to
      generate basal forebrain cholinergic neurons via hedgehog signaling.
AB  - Basal forebrain cholinergic neurons (bfCNs) which provide innervation to the
      hippocampus and cortex, are required for memory and learning, and are primarily
      affected in Alzheimer's Disease (AD), resulting in related cognitive decline.
      Therefore generation of a source of bfCNs from human pluripotent stem cells
      (hPSCs) is crucial for in vitro disease modeling and development of novel AD
      therapies. In addition, for the advancement of regenerative approaches there is a
      requirement for an accurate developmental model to study the neurogenesis and
      survival of this population. Here we demonstrate the efficient production of
      bfCNs, using a novel embryoid body (EB) based non-adherent differentiation (NAdD)
      protocol. We establish a specific basal forebrain neural stem cell (NSC)
      phenotype via expression of the basal forebrain transcription factors NKX2.1 and
      LHX8, as well as the general forebrain marker FOXG1. We present evidence that
      this lineage is achieved via recapitulation of embryonic events, with induction
      of intrinsic hedgehog signaling, through the use of a 3D non-adherent
      differentiation system. This is the first example of hPSC-derived basal forebrain
      like NSCs, which are scalable via self-renewal in prolonged culture. Furthermore
      upon terminal differentiation these basal forebrain-like NSCs generate high
      numbers of cholinergic neurons expressing the specific markers ChAT, VACht and
      ISL1. These hPSC-derived bfCNs possess characteristics that are crucial in a
      model to study AD related cholinergic neuronal loss in the basal forebrain.
      Examples are expression of the therapeutic target p75(NTR), the release of
      acetylcholine, and demonstration of a mature, and functional electrophysiological
      profile. In conclusion, this work provides a renewable source of human functional
      bfCNs applicable for studying AD specifically in the cholinergic system, and also
      provides a model of the key embryonic events in human bfCN development. 

PMID- 24013067
TI  - Surgical management of extensive jugular paragangliomas: 10-year-experience with
      a large cohort of patients in China.
AB  - OBJECTIVE: Jugular paraganglioma (JP) is a rare vascular lesion. Surgical
      treatment is challenging as differing degrees of skull base invasion and cranial
      nerve infiltration complicate the procedure. The infra-temporal fossa type A
      (IFTA) approach has been advocated as the primary surgical strategy. However, due
      to the small number of cases in each report and the different categories of JP,
      no study has provided concrete results about the effectiveness and safeness of
      IFTA in treating different categories of JP. METHODS: We reviewed our
      institutional experience in the management of patients with JP. RESULTS: Records
      of 89 JP patients were reviewed. The IFTA procedure appears equally effective in
      preserving lower cranial nerve function for both extradural and intracranial
      extension JP. Use of the IFTA approach for intracranial JP poses a significant
      risk of post-operative morbidity including facial nerve dysfunction, tumor
      recurrence and CSF leak. CONCLUSION: Improvements in the standard IFTA approach
      are necessary for improved outcomes in patients with intracranial extension JP.

PMID- 24013069
TI  - TRAP assists membrane protein topogenesis at the mammalian ER membrane.
AB  - Membrane protein insertion and topogenesis generally occur at the Sec61
      translocon in the endoplasmic reticulum membrane. During this process, membrane
      spanning segments may adopt two distinct orientations with either their N- or C
      terminus translocated into the ER lumen. While different topogenic determinants
      in membrane proteins, such as flanking charges, polypeptide folding, and
      hydrophobicity, have been identified, it is not well understood how the
      translocon and/or associated components decode them. Here we present evidence
      that the translocon-associated protein (TRAP) complex is involved in membrane
      protein topogenesis in vivo. Small interfering RNA (siRNA)-mediated silencing of
      the TRAP complex in HeLa cells enhanced the topology effect of mutating the
      flanking charges of a signal-anchor, but not of increasing signal hydrophobicity.
      The results suggest a role of the TRAP complex in moderating the 'positive
      inside' rule. 

PMID- 24013070
TI  - Wafer-scale nanowell array patterning based electrochemical impedimetric
      immunosensor.
AB  - We have reported that nanowell array (NWA) can enhance electrochemical detection
      of molecular binding events by controlling the binding sites of the captured
      molecules. Using NWA biosensor based amperometric analysis, we have detected
      biological macromolecules such as DNA, protein or aptamers at low concentrations.
      In this research, we developed an impedimetric immunosensor based on wafer-scale
      NWA for electrochemical detection of stress-induced-phosphoprotein-1 (STIP-1). In
      order to develop NWA sensor through the cost-effective combination of high
      throughput nanopattern, the NWA electrode was fabricated on Si wafer by krypton
      fluoride (KrF) stepper semiconductor process. Finally, 12,500,000 ea nanowell
      with a 500 nm diameter was fabricated on 4 mm * 2 mm substrate. Next, by using
      these electrodes, we measured impedance to quantify antigen binding to the
      immunoaffinity layer. The limit of detection (LOD) of the NWA was improved about
      100-fold compared to milli-sized electrodes (4 mm * 2 mm) without an NWA. These
      results suggest that wafer-scale NWA immunosensor will be useful for biosensing
      applications because their interface response is appropriate for detecting
      molecular binding events.

PMID- 24013071
TI  - Ontogeny of the avian intestinal immunoglobulin repertoire: modification in CDR3
      length and conserved VH-pseudogene usage.
AB  - Immunoglobulins play an important role in maintenance of mucosal homeostasis in
      the gut. The antigen binding specificity of these immunoglobulins depends for a
      large part on the hypervariable CDR3 region. To gain knowledge about isotype
      specific development of the CDR3 repertoire we examined CDR3 spectratypes at
      multiple time points between 4 and 70 days post hatch. In order to identify
      clonal expansions deviation from the normal distribution (SS) and the average
      CDR3 length was calculated. IgA-CDR3 regions were studied in more detail by DNA
      sequence analysis at day 7 and 70 and preferential VH pseudogene usage was
      estimated. The SS of CDR3 repertoires of the IgM, IgG and IgA isotypes
      successively increased, but for each isotype this increase was transiently. The
      length of the CDR3 regions decreased with age for IgM becoming similar to the
      CDR3 length of IgA at day 70. The IgA- and IgG-CDR3 lengths did not change with
      age. On average, the CDR3 length of IgA was the shortest. IgA CDR3 sequences were
      similar between animals aged 7 and 70 days. A limited number of pseudogenes was
      used, and no differences in pseudogene usage were observed between animals aged 7
      and 70 days. Of the identified VH pseudogenes, half of the sequences used VH15,
      whilst a number of the pseudogenes were not used at all. We conclude that CDR3
      spectratype profiles change during aging, whilst at the CDR3-sequence level,
      variation in VH pseudogene usage for ileal IgA is limited suggesting conservation
      during ontogeny. 

PMID- 24013072
TI  - Recent advances in diagnosis and treatment of transitional cell carcinoma of the
      bladder.
AB  - The management of transitional cell carcinoma of the bladder (TCCB) presents a
      challenge to urological surgeons due to the diversity of patient factors, stage
      at presentation and propensity for disease recurrence and progression. Advances
      in the last decade have seen an evolution in techniques for diagnosis, treatment
      and ongoing surveillance. A good understanding of our patients, the disease and
      the available diagnostic and therapeutic options is essential for the management
      of this condition. We review the current literature focusing on the merits of
      recent advances in this field. Given the breadth of the subject, we have
      deliberately selected only the most relevant and recent advances already in
      clinical use. 

PMID- 24013073
TI  - Capsaicin pretreatment increased the bioavailability of cyclosporin in rats:
      involvement of P-glycoprotein and CYP 3A inhibition.
AB  - Capsaicin (CAP), the main ingredient responsible for the hot pungent taste of
      chilli peppers. This study investigated the effect of CAP on the pharmacokinetics
      of Cyclosporin A (CyA) in rats and the mechanism of this food-drug interaction.
      The results indicated that after 7 days of low or middle dose of CAP (0.3 or 1.0
      mg/kg), the blood concentration of CyA was not significantly changed compared
      with that of vehicle-treated rats, whereas the blood concentration of CyA in high
      dose group (3.0 mg/kg) was significantly increased. The total clearance (CL/F) of
      CyA was decreased, and the bioavailability was significantly increased to about
      1.44-fold of that in vehicle-treated rats after 7 days of high dose CAP
      treatment. At this time, the P-gp and CYP3A1/2 in the liver and intestine were
      decreased at both the mRNA and protein levels. These results demonstrated that
      chronic ingestion of high doses of CAP will increase the bioavailability of CyA
      to a significant extent in rats and the food-drug interaction between CAP and CyA
      appears to be due to modulation of P-gp and CYP3A gene expression by CAP, with
      differential dose-dependence.

PMID- 24013068
TI  - The tiers and dimensions of evasion of the type I interferon response by human
      cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) is a member of the beta-herpesvirus family that
      invariably occupies hosts for life despite a consistent multi-pronged antiviral
      immune response that targets the infection. This persistence is enabled by the
      large viral genome that encodes factors conferring a wide assortment of
      sophisticated, often redundant phenotypes that disable or otherwise manipulate
      impactful immune effector processes. The type I interferon system represents a
      first line of host defense against infecting viruses. The physiological reactions
      induced by secreted interferon act to effectively block replication of a broad
      spectrum of virus types, including HCMV. As such, the virus must exhibit
      counteractive mechanisms to these responses that involve their inhibition,
      tolerance, or re-purposing. The goal of this review is to describe the impact of
      the type I interferon system on HCMV replication and to showcase the number and
      diversity of strategies employed by the virus that allow infection of hosts in
      the presence of interferon-dependent activity. 

PMID- 24013074
TI  - Photoprotective effects of Romanian propolis on skin of mice exposed to UVB
      irradiation.
AB  - We aimed at investigating the antioxidant, antiinflamatory, antiapoptotic and
      antigenotoxic effects of a Romanian Propolis (RP) extract in two concentrations
      (RP1 3 mg, respectively RP2 1.5 mg polyphenols/cm(2)), topically administered,
      either prior to or after UVB exposure, in a Swiss mouse model. Our results showed
      that both concentrations of RP extract, independent of the time of
      administration, significantly attenuated the malondialdehyde (MDA) formation and
      restored glutathione peroxidase (GPx) activity. However, the 8-hydroxy-2-deoxy
      guanosine (8-oxo-dG), nitric oxide (NO) and glutathione (GSH) levels were not
      influenced by UVB exposure and RP treatment. Interleukin (IL)-6 levels were
      significantly decreased by RP treatment, both before and after UVB-exposure. RP2
      extract, in both regimens, significantly reduced the epidermal hyperplasia and
      dermal inflammation, whereas RP1 pre-treatment diminished only the dermal
      inflammation. The effect of our RP extract in terms of reduction of sunburn cell
      formation and of activated caspase-3 and TUNEL-positive cells was observed in
      both subsets of the experiment, RP2 having a slightly better protective effect as
      compared to RP1. The antigenotoxic effect of RP was demonstrated by significantly
      reduced cyclobutane pyrimidine dimers (CPDs) formation. Our results suggest that
      RP extract might be a potential chemopreventive candidate by modulation of
      multiple UVB-induced signaling pathways in skin.

PMID- 24013075
TI  - Standard metabolic rate of the bed bug, Cimex lectularius: effects of
      temperature, mass, and life stage.
AB  - Metabolic rates provide important information about the biology of organisms. For
      ectothermic species such as insects, factors such as temperature and mass heavily
      influence metabolism, but these effects differ considerably between species. In
      this study we examined the standard metabolic rate of the bed bug, Cimex
      lectularius L. We used closed system respirometry and measured both O2
      consumption and CO2 production across a range of temperatures (10, 20, 25, 30, 35
      degrees C) and life stages, while also accounting for activity. Temperature had a
      stronger effect on the mass specific .VO2 (mlg(-1)h(-1)) of mated males
      (Q10=3.29), mated females (Q10=3.19), unmated males (Q10=3.09), and nymphs that
      hatched (first instars, Q10=3.05) than on unmated females (Q10=2.77) and nymphs
      that molted (second through fifth instars, Q10=2.78). First instars had
      significantly lower respiratory quotients (RQ) than all other life stages. RQ of
      all stages was not affected by temperature. .VO2 (mlh(-1)) scaled more with mass
      than values previously reported for other arthropods or that would be predicted
      by the 3/4-power law. The results are used to understand the biology and ecology
      of the bed bug.

PMID- 24013076
TI  - Effects of time constraints on clinician-computer interaction: a study on
      information synthesis from EHR clinical notes.
AB  - BACKGROUND: Time is a measurable and critical resource that affects the quality
      of services provided in clinical practice. There is limited insight into the
      effects of time restrictions on clinicians' cognitive processes with the
      electronic health record (EHR) in providing ambulatory care. OBJECTIVE: To
      understand the impact of time constraints on clinicians' synthesis of text-based
      EHR clinical notes. METHODS: We used an established clinician cognitive framework
      based on a think-aloud protocol. We studied interns' thought processes as they
      accomplished a set of four preformed ambulatory care clinical scenarios with and
      without time restrictions in a controlled setting. RESULTS: Interns most often
      synthesized details relevant to patients' problems and treatment, regardless of
      whether or not the time available for task performance was restricted. In
      contrast to previous findings, subsequent information commonly synthesized by
      clinicians related most commonly to the chronology of clinical events for the
      unrestricted time observations and to investigative procedures for the time
      restricted sessions. There was no significant difference in the mean number of
      omission errors and incorrect deductions when interns synthesized the EHR
      clinical notes with and without time restrictions (3.5+/-0.5 vs. 2.3+/-0.5,
      p=0.14). CONCLUSION: Our results suggest that the incidence of errors during
      clinicians' synthesis of EHR clinical notes is not increased with modest time
      restrictions, possibly due to effective adjustments of information processing
      strategies learned from the usual time-constrained nature of patient visits.
      Further research is required to investigate the effects of similar or more
      extreme time variations on cognitive processes employed with different levels of
      expertise, specialty, and with different care settings.

PMID- 24013077
TI  - The extracellular protein VlsE is destabilized inside cells.
AB  - We use U2OS cells as in vivo "test tubes" to study how the same cytoplasmic
      environment has opposite effects on the stability of two different proteins.
      Protein folding stability and kinetics were compared by fast relaxation imaging,
      which combines a temperature jump with fluorescence microscopy of FRET (Forster
      resonance energy transfer)-labeled proteins. While the stability of the
      cytoplasmic enzyme PGK (phosphoglycerate kinase) increases in cells, the
      stability of the cell surface antigen VlsE, which presumably did not evolve for
      stability inside cells, decreases. VlsE folding also slows down more than PGK
      folding in cells, relative to their respective aqueous buffer kinetics. Our FRET
      measurements provide evidence that VlsE is more compact inside cells than in
      aqueous buffer. Two kinetically distinct protein populations exist inside cells,
      making a connection with previous in vitro crowding studies. In addition, we
      confirm previous studies showing that VlsE is stabilized by 150mg/mL of the
      carbohydrate crowder Ficoll, even though it is destabilized in the cytoplasm
      relative to aqueous buffer. We propose two mechanisms for the observed
      destabilization of VlsE in U2OS cells: long-range interactions competing with
      crowding or shape-dependent crowding favoring more compact states inside the cell
      over the elongated aqueous buffer native state. 

PMID- 24013078
TI  - Identification of 30 MYB transcription factor genes and analysis of their
      expression during abiotic stress in peanut (Arachis hypogaea L.).
AB  - The MYB superfamily constitutes one of the most abundant groups of transcription
      factors and plays central roles in developmental processes and defense responses
      in plants. In the work described in this article, 30 unique peanut MYB genes that
      contained full-length cDNA sequences were isolated. The 30 genes were grouped
      into three categories: one R1R2R3-MYB, nine R2R3-MYBs and 20 MYB-related members.
      The sequence composition of the R2 and R3 repeats was conserved among the nine
      peanut R2R3-MYB proteins. Phylogenetic comparison of the members of this
      superfamily between peanut and Arabidopsis revealed that the putative functions
      of some peanut MYB proteins were clustered into the Arabidopsis functional
      groups. Expression analysis during abiotic stress identified a group of MYB genes
      that responded to at least one stress treatment. This is the first comprehensive
      study of the MYB gene family in peanut. 

PMID- 24013079
TI  - Genome-wide identification and expression profile of homeodomain-leucine zipper
      Class I gene family in Cucumis sativus.
AB  - The HD-Zip proteins comprise one of the largest families of transcription factors
      in plants. HD-Zip genes have been grouped into four different classes: HD-Zip I
      to IV. In this study, we described the identification and structural
      characterization of Class I HD-Zip genes in cucumber. A complete set of 13 HD-Zip
      I genes were identified in the cucumber genome using Blast search tools and
      phylogeny. The cucumber HD-Zip I family contained a smaller number of identified
      genes compared to other higher plants such as Arabidopsis and maize due to the
      absence of recent gene duplication events. Chromosomal location of these genes
      revealed that they are distributed unevenly across 5 of 7 chromosomes. Tissue
      specific expression profiles showed that 13 cucumber HD-Zip I genes were
      expressed in at least one of the tissues, which suggested that cucumber HD-Zip I
      genes took part in many cellular processes. The transcript abundance level
      analysis during abiotic stress conditions (NaCl, ABA and low temperature
      treatments) identified a group of HD-Zip I genes that responded to one or more
      treatments.

PMID- 24013080
TI  - Transcriptomic analysis of incised leaf-shape determination in birch.
AB  - Plant researchers have focused much attention on leaf shape because of its
      importance in the identification. To evaluate the impact of intraspecies leaf
      shape variation on the transcriptome, a series of Betula pendula 'Dalecarlica'
      and B. pendula saplings were generated through tissue culture. The leaf shapes
      and transcriptomes of B. pendula 'Dalecarlica' clones were compared with those of
      B. pendula clones. The leaf shape of B. pendula 'Dalecarlica' was incised and
      that of B. pendula was ovate. Transcriptome data revealed numerous changes in
      gene expression between B. pendula 'Dalecarlica' and B. pendula, including
      upregulation of 8767 unigenes and downregulation of 8379 unigenes in B. pendula
      'Dalecarlica'. A pathway analysis revealed that the transport and signal
      transduction of auxin were altered in 'Dalecarlica', which may have contributed
      to its altered leaf shape. These results shed light on variation in birch leaf
      shape and help identify important genes for the genetic engineering of birch
      trees.

PMID- 24013081
TI  - GJB2-associated hearing loss undetected by hearing screening of newborns.
AB  - The hearing loss caused by GJB2 mutations is usually congenital in onset,
      moderate to profound in degree, and non-progressive. The objective of this study
      was to study genotype/phenotype correlations and to document 14 children with
      biallelic GJB2 mutations who passed newborn hearing screening (NHS). Genetic
      testing for GJB2 mutations by direct sequencing was performed on 924 individuals
      (810 families) with hearing loss, and 204 patients (175 families) were found to
      carry biallelic GJB2 mutations. NHS results were obtained through medical
      records. A total of 18 pathological mutations were identified, which were
      subclassified as eight inactivating and 10 non-inactivating mutations. p.I128M
      and p.H73Y were identified as novel missense GJB2 mutations. Of the 14 children
      with biallelic GJB2 mutations who passed NHS, eight were compound heterozygotes
      and 3 were homozygous for the c.235delC mutation in GJB2, and the other three
      combinations of non-c.235delC mutations identified were p.Y136X-p.G45E/p.V37I
      heterozygous, c.512ins4/p.R143W heterozygous, and p.V37I/p.R143W heterozygous.
      These 14 cases demonstrate that the current NHS does not identify all infants
      with biallelic GJB2 mutations. They suggest that the frequency of non-penetrance
      at birth is approximately 6.9% or higher in DFNB1 patients and provide further
      evidence that GJB2 hearing loss may not always be congenital in onset. 

PMID- 24013082
TI  - Assessment of HER-2 gene overexpression in Isfahan province breast cancer
      patients using Real Time RT-PCR and immunohistochemistry.
AB  - PURPOSE: Overexpression of proto-oncogene HER-2 is one of the main molecular
      markers of breast cancer involved in prognosis and diagnosis and also in
      trastuzumab therapy. Thus, a request for the evaluation of HER-2 status in breast
      cancer has been increasing. The aim of our study was assessment of HER-2
      overexpression in malignant and benign breast cancer specimens by Real Time RT
      PCR technique and comparison of its results with IHC outcomes. METHODS: Twenty
      benign and sixty malignant breast cancers in addition to fifteen normal breast
      tissue specimens were analyzed by Real Time RT-PCR method. Fresh tissue samples
      were disrupted by mortar and pestle. A syringe and a needle were used for
      complete homogenization of the tissues. The RNA was then isolated from the
      samples and converted to cDNA. A standard curve was initially plotted using
      BioEasy SYBR Green I and then all 95 specimens were studied by Real Time RT-PCR
      using 2(-DeltaDeltaCt) method. RESULTS: 23.3% of 60 malignant specimens showed
      HER-2 overexpression, while all of the benign samples represented the normal
      expression level of HER-2 gene. The concordance rate between the results of Real
      Time RT-PCR and IHC was 86.6%. CONCLUSION: Real Time RT-PCR method is an almost
      reliable technique and at least can be used as a complementary method for
      confirming IHC results. This is emanated from relatively high rate of concordance
      between outcomes of IHC test, as a routine method of detecting the HER-2 gene
      expression status, and Real Time RT-PCR technique.

PMID- 24013083
TI  - A new small supernumerary marker chromosome involving 14pter -> q12 in a child
      with severe neurodevelopmental retardation: case report and literature review.
AB  - Unstable, gene-rich pericentric regions have been associated with various
      structural aberrations including small supernumerary marker chromosomes (sSMCs).
      We hereby report on a new sSMC derived from chromosome 14, generating trisomy
      14pter -> q12 in a child with severe neurodevelopmental delay. The patient
      featured facial dysmorphism, generalized hypotonia, transverse palmar creases,
      structural brain abnormality, and severe cognitive and motor impairment.
      Literature review indicated this to be a unique case of sSMC 14 which was only
      composed of pter -> q12, and the phenotype secondary to duplications of the
      similar region partially overlaps with the phenotype reported in this study. The
      genetic analysis on our case helps to better delineate karyotype-phenotype
      correlations between proximal trisomy 14 and associated clinical phenomena, and
      we also propose that the involved chromosomal regions may contain dosage
      sensitive genes which are important for the development.

PMID- 24013084
TI  - Polymorphism of BMP4 gene in Indian goat breeds differing in prolificacy.
AB  - Bone morphogenetic proteins (BMPs) are members of the TGF-beta (transforming
      growth factor-beta) superfamily, of which BMP4 is the most important due to its
      crucial role in follicular growth and differentiation, cumulus expansion and
      ovulation. Reproduction is a crucial trait in goat breeding and based on the
      important role of BMP4 gene in reproduction it was considered as a possible
      candidate gene for the prolificacy of goats. The objective of the present study
      was to detect polymorphism in intronic, exonic and 3' un-translated regions of
      BMP4 gene in Indian goats. Nine different goat breeds (Barbari, Beetal, Black
      Bengal, Malabari, Jakhrana (Twinning>40%), Osmanabadi, Sangamneri (Twinning 20
      30%), Sirohi and Ganjam (Twinning<10%)) differing in prolificacy and geographic
      distribution were employed for polymorphism scanning. Cattle sequence
      (AC_000167.1) was used to design primers for the amplification of a targeted
      region followed by direct DNA sequencing to identify the genetic variations.
      Single nucleotide polymorphisms (SNPs) were not detected in exon 3, the intronic
      region and the 3' flanking region. A SNP (G1534A) was identified in exon 2. It
      was a non-synonymous mutation resulting in an arginine to lysine change in a
      corresponding protein sequence. G to A transition at the 1534 locus revealed two
      genotypes GG and GA in the nine investigated goat breeds. The GG genotype was
      predominant with a genotype frequency of 0.98. The GA genotype was present in the
      Black Bengal as well as Jakhrana breed with a genotype frequency of 0.02. A
      microsatellite was identified in the 3' flanking region, only 20 nucleotides
      downstream from the termination site of the coding region, as a short sequence
      with more than nineteen continuous and repeated CA dinucleotides. Since the gene
      is highly evolutionarily conserved, identification of a non-synonymous SNP
      (G1534A) in the coding region gains further importance. To our knowledge, this is
      the first report of a mutation in the coding region of the caprine BMP4 gene. But
      whether the reproduction trait of goat is associated with the BMP4 polymorphism,
      needs to be further defined by association studies in more populations so as to
      delineate an effect on it. 

PMID- 24013085
TI  - Identification and characterization of a nanog homolog in Japanese flounder
      (Paralichthys olivaceus).
AB  - The homeodomain-containing transcription factor nanog plays a key role in
      maintaining the pluripotency and self-renewal of embryonic stem cells in mammals.
      Stem cells offered as a significant and effective tool for generation of
      transgenic animals and preservation of genetic resources. The molecular genetic
      organization and expression of nanog gene in marine fish have not been reported
      yet. In this study, we isolated and characterized the flounder nanog gene as a
      first step towards understanding the mechanism of the plurpotency of fish stem
      cells and develop a potential molecular marker to identify the stem cells in vivo
      and in vitro. Phylogenetic, gene structure and chromosome synteny analysis
      provided the evidence that Po-nanog is homologous to the mammalian nanog gene.
      Protein sequence comparison showed that flounder Nanog shared low similarity with
      other vertebrate orthologs except for a conserved homeodomain. Quantitative RT
      PCR analysis showed that flounder nanog was maternally expressed, and the
      transcripts were present from the one-cell stage to the neurula stage with the
      peaking at blastula stage. Whole mount in situ hybridization analyses
      demonstrated that the transcripts were present in all blastomeres of the early
      embryo. Tissue distribution analysis indicated that nanog was detectable only in
      gonads. Further, the expression was significantly high in ovary than in testis.
      In situ hybridization revealed that the transcripts were located in the cytoplasm
      of the oogonia and oocytes in ovary, only in the spermatogonia but no
      spermatocytes or spermatids in testis. The promoter region was also analyzed to
      have several basal core promoter elements and transcription factor binding sites.
      All these results suggest that Po-Nanog may have a conservative function between
      teleosts and mammals. 

PMID- 24013087
TI  - Place shaping to create health and wellbeing using health impact assessment:
      health geography applied to develop evidence-based practice.
AB  - In a political milieu where there is pressure towards localised and participative
      decisionmaking, and an environment of global recession and environmental
      degradation, it is crucial that population health considerations inform strategic
      decisions. The paper puts forward 'place shaping to create health and wellbeing'
      as a strategic tool, drawing on ideas that are fundamental in health geography,
      and argues that this is an important emerging application of Health Impact
      Assessment (HIA), as part of evidence-based practice. These views developed
      primarily from case study work in the North East of England aiming to enhance
      health and wellbeing in a population with significant health disadvantages. 

PMID- 24013088
TI  - Housing conditions and mental health of orphans in South Africa.
AB  - Literature from the developed world suggests that poor housing conditions and
      housing environments contribute to poor mental health outcomes, although research
      results are mixed. This study investigates the relationship between housing
      conditions and the socio-emotional health of orphans and vulnerable children
      (OVC) in South Africa. The results of the study are mainly inconclusive, although
      it is suggested that methodological considerations play a vital role in
      explaining the mixed results. However, a positive relationship was found between
      living in informal settlements and better socio-emotional health of the OVC. We
      speculate that the historical context of informal settlement formation in South
      Africa helps to explain this unexpected result. 

PMID- 24013086
TI  - Structure and function of the DNA ligases encoded by the mammalian LIG3 gene.
AB  - Among the mammalian genes encoding DNA ligases (LIG), the LIG3 gene is unique in
      that it encodes multiple DNA ligase polypeptides with different cellular
      functions. Notably, this nuclear gene encodes the only mitochondrial DNA ligase
      and so is essential for this organelle. In the nucleus, there is significant
      functional redundancy between DNA ligase IIIalpha and DNA ligase I in excision
      repair. In addition, DNA ligase IIIalpha is essential for DNA replication in the
      absence of the replicative DNA ligase, DNA ligase I. DNA ligase IIIalpha is a
      component of an alternative non-homologous end joining (NHEJ) pathway for DNA
      double-strand break (DSB) repair that is more active when the major DNA ligase IV
      dependent pathway is defective. Unlike its other nuclear functions, the role of
      DNA ligase IIIalpha in alternative NHEJ is independent of its nuclear partner
      protein, X-ray repair cross-complementing protein 1 (XRCC1). DNA ligase IIIalpha
      is frequently overexpressed in cancer cells, acting as a biomarker for increased
      dependence upon alternative NHEJ for DSB repair and it is a promising novel
      therapeutic target.

PMID- 24013089
TI  - Lest we forget: why the use of chemical weapons must not go unchallenged.

PMID- 24013090
TI  - Patient-reported outcome measures: an on-line system empowering patient choice.
AB  - An innovative web-based system was developed to allow patient-reported outcome
      measures (PROMs) to be easily administered. Stakeholders guided the design and
      implementation. The software gives patients access to their current and previous
      scores. This pilot study focused on patients undergoing arthroscopic subacromial
      decompression, evaluated using the Oxford shoulder score (OSS). Patients showing
      good improvement in their OSS were offered the choice to return for routine
      follow-up clinic appointments, or continue rehabilitation, reassured by their
      improved score. Thirty-six of 117 patients were eligible. Thirty of these (83%)
      were opted to avoid further clinics. PROMs 2.0 can be used for any medical
      intervention with a validated PROM. Evolution and refinement is ongoing. Funding
      has been granted for 12 primary and secondary healthcare trusts to implement
      PROMs 2.0. Further work is needed to assess economic impact, patient views and
      satisfaction with the process. 

PMID- 24013091
TI  - Electronic health record use and preventive counseling for US children and
      adolescents.
AB  - The objective was to assess whether rates of preventive counseling delivered at
      well child visits (WCVs) differ for practices with basic, fully functional, or no
      electronic health record (EHR). Cross-sectional analyses of WCVs included in the
      National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical
      Care Survey Electronic Medical Records Supplement, 2007-2010 were performed.
      Practices with fully functional EHRs documented delivery of 34% more counseling
      topics than those without an EHR. WCVs with a fully functional EHR lasted 3.5
      more minutes than those with a basic EHR. Overall, for each additional 10 min,
      12% more topics were covered, regardless of EHR functionality. Further studies
      should assess the impact of such systems on the quality of patient care during
      preventive care visits and on health outcomes. 

PMID- 24013092
TI  - The impact of cold acclimation and hibernation on antioxidant defenses in the
      ground squirrel (Spermophilus citellus): an update.
AB  - Any alteration in oxidative metabolism is coupled with a corresponding response
      by an antioxidant defense (AD) in appropriate subcellular compartments. Seasonal
      hibernators pass through circannual metabolic adaptations that allow them to
      either maintain euthermy (cold acclimation) or enter winter torpor with body
      temperature falling to low values. The present study aimed to investigate the
      corresponding pattern of AD enzyme protein expressions associated with these
      strategies in the main tissues involved in whole animal energy homeostasis: brown
      and white adipose tissues (BAT and WAT, respectively), liver, and skeletal
      muscle. European ground squirrels (Spermophilus citellus) were exposed to low
      temperature (4 +/- 1  degrees C) and then divided into two groups: (1) animals
      fell into torpor (hibernating group) and (2) animals stayed active and euthermic
      for 1, 3, 7, 12, or 21 days (cold-exposed group). We examined the effects of cold
      acclimation and hibernation on the tissue-dependent protein expression of four
      enzymes which catalyze the two-step detoxification of superoxide to water:
      superoxide dismutase 1 and 2 (SOD 1 and 2), catalase (CAT), and glutathione
      peroxidase (GSH-Px). The results showed that hibernation induced an increase of
      AD enzyme protein expressions in BAT and skeletal muscle. However, AD enzyme
      contents in liver were largely unaffected during torpor. Under these conditions,
      different WAT depots responded by elevating the amounts of specific enzymes, as
      follows: SOD 1 in retroperitoneal WAT, GSH-Px in gonadal WAT, and CAT in
      subcutaneous WAT. Similar perturbations of AD enzymes contents were seen in all
      tissues during cold acclimation, often in a time-dependent manner. It can be
      concluded that BAT and muscle AD capacity undergo the most dramatic changes
      during both cold acclimation and hibernation, while liver is relatively
      unaffected by either condition. Additionally, this study provides a basis for
      further metabolic study that will illuminate the causes of these tissue-specific
      AD responses, particularly the novel finding of distinct responses by different
      WAT depots in hibernators.

PMID- 24013094
TI  - Are intra-gastric adjustable balloon system safe? A case series.
AB  - INTRODUCTION: Intra-gastric balloons have been in use as an aide to weight loss.
      Since its introduction, it has evolved from air filled to saline filled intra
      gastric balloons. The SPATZ-ABS is a new adjustable saline filled balloon.
      PRESENTATION OF CASE: Three patients have presented to our hospital as
      emergencies due to complications arising from this balloon. Two of these patients
      required emergency laparotomy and resection of small bowel due to pressure
      necrosis effects of the anchoring device. One patient had migration of the device
      into the duodenum that was removed endoscopically. Of the 2 patients who
      underwent a laparotomy, one patient did not have any symptoms or signs that
      correlated with the intra-operative findings. DISCUSSION: The anchoring device
      meant to prevent the intra-gastric balloon from migrating distally has migrated
      in three patients. To our knowledge, there has been no reported incident of
      migration of this device. These serious complications pose a risk to patients
      having these balloons fitted. CONCLUSION: There is a need to study our experience
      with a larger population of patients who have had this device inserted. Its
      safety needs to be questioned and its design may need to be addressed.

PMID- 24013093
TI  - Gamma-tocopherol attenuates moderate but not severe colitis and suppresses
      moderate colitis-promoted colon tumorigenesis in mice.
AB  - Inflammation can promote colon cancer. Mechanistic studies indicate that gamma
      tocopherol (gammaT), a major form of vitamin E in diets, has anti-inflammatory
      and anticancer properties. Here we investigated the effectiveness of gammaT and a
      mixture of tocopherols against colitis and colitis-promoted colon tumorigenesis
      in male BALB/c mice. gammaT or mixed tocopherols (at 0.1% diet) did not show any
      effect on colon tumorigenesis induced by azoxymethane (AOM, 10mg/kg) with three
      cycles of dextran sodium sulfate (DSS at 1.5-2.5%). gammaT failed to exhibit
      protection of severe colitis caused by three cycles of DSS at 2.5%. In contrast,
      when AOM-initiated carcinogenesis was promoted by relatively mild colitis induced
      by one-cycle DSS (1.5%), gammaT, but not mixed tocopherols, suppressed total
      multiplicity of macroscopic adenomas (P=0.06) and large adenomatous polyps
      (>2mm(2), P<0.05) by 60 and 85%, respectively. gammaT also significantly
      decreased tumor multiplicity (>2mm(2)) induced by AOM with two cycles of 1.5% DSS
      even when dietary supplementation was started after AOM injection. Consistently,
      gammaT but not mixed tocopherols attenuated DSS (1.5%)-induced colon inflammation
      and damage as well as formation of atypical glandular hyperplasia. Mice
      supplemented with tocopherols had high fecal excretion of 13'-carboxychromanol, a
      long-chain vitamin E metabolite shown to have potent anti-inflammatory
      activities. Our study demonstrates that gammaT is able to alleviate moderate but
      not severe colitis and its promoted tumorigenesis, and indicates that
      inflammation severity should be considered in evaluating anticancer effectiveness
      of chemoprevention agents. 

PMID- 24013095
TI  - Association analysis of the DISC1 gene with schizophrenia in the Japanese
      population and DISC1 immunoreactivity in the postmortem brain.
AB  - The Disrupted-in-Schizophrenia 1 (DISC1) gene plays a role in the regulation of
      neural development. Previous evidence from genetic association and biological
      studies implicates the DISC1 gene as having a role in the pathophysiology of
      schizophrenia. In the present study, we explored the association between DISC1
      missense mutation rs821616 (Ser704Cys) single nucleotide polymorphism (SNP) and
      four other SNPs (rs1772702, rs1754603, rs821621, rs821624) in the related
      haplotype block and schizophrenia in the Japanese population. We could not find a
      significant association of selected SNPs with schizophrenia after correction for
      multiple testing. We performed a meta-analysis of the Ser704Cys variant in
      schizophrenia using data from the present study and five previous Japanese
      population studies, and found no association with schizophrenia. We also examined
      DISC1 immunoreactivity in postmortem prefrontal cortex specimens of schizophrenia
      patients compared to control samples. The immunoreactivity revealed a significant
      decrease of DISC1 protein expression in the schizophrenia samples after ruling
      out potential confounding factors. However, the Ser704Cys variant did not show
      effects on DISC1 immunoreactivity. These results provide evidence that this
      functional genetic variation of DISC1 do not underlie the pathophysiology of
      schizophrenia in the Japanese population. 

PMID- 24013096
TI  - Reorganization of motor circuits after neonatal hemidecortication.
AB  - It is well recognized that a juvenile brain is more plastic than an adult brain
      and often undergoes better functional recovery following cortical injury. Infants
      treated with hemispherectomy to cure intractable epilepsy often exhibit restored
      normal motor function in the extremities contralateral to the lesion. Neuronal
      mechanisms of functional recovery after such a large cortical damage at a young
      age have been studied using animals with a similar lesion, hemidecortication. In
      such animals, descending pathways from the undamaged sensorimotor cortex to the
      ipsilateral forelimb motoneurons are reorganized as restoring normal motor
      function of the forelimb contralateral to the injury. Similar aberrant pathways
      from the motor cortex to the ipsilateral motoneurons are also generated following
      suppression of cortical activity in the other hemisphere, suggesting the
      development of contralateral connections in an activity-dependent manner in
      normal animals. Thus, formation of ipsilateral descending pathways following
      neonatal hemidecortication might be due to a loss of balance in cortical activity
      between the two hemispheres. Studies using animal models of neonatal cortical
      injury can reveal mechanisms of neural development and may help to establish
      therapeutic strategies to facilitate recovery from human juvenile cortical
      injury. 

PMID- 24013097
TI  - miRNA-141, downregulated in pancreatic cancer, inhibits cell proliferation and
      invasion by directly targeting MAP4K4.
AB  - miRNAs are associated with various types of cancer due to their ability to affect
      expression of genes that modulate tumorigenesis. In this study, we explored the
      role of miR-141 in pancreatic cancer. The analysis of clinical characteristics
      showed that miR-141 was significantly downregulated in tissues and cell lines of
      pancreatic cancer. Moreover, the decreased miR-141 level was significantly
      associated with tumor size and TNM stage, as well as lymph node and distant
      metastasis. Meanwhile, both Kaplan-Meier and multivariate survival analysis
      showed decreased miR-141 were associated with overall survival. Overexpression of
      miR-141 in pancreatic cancer cells inhibited cell proliferation, clonogenicity,
      and invasion; induced G1 arrest and apoptosis; and enhanced chemosensitivity. To
      understand how miR-141 mediates the phenotype of pancreatic cancer cells, a
      bioinformatics tool was used to identify MAP4K4 as a potential target of miR-141.
      The Dual-Luciferase reporter gene assay showed that miR-141 binds directly to the
      3'-untranslated region (3'UTR) of MAP4K4 to inhibit MAP4K4 expression. Western
      blot and quantitative real-time PCR (qRT-PCR) analyses revealed that MAP4K4
      expression was inversely correlated with miR-141 expression both in pancreatic
      cancer samples and cell lines. Knockdown of MAP4K4 inhibited cell proliferation,
      clonogenicity, and invasion, induced G1 arrest and apoptosis, and enhanced
      chemosensitivity. In a nude mouse xenograft model, both overexpression of miR-141
      and knockdown of MAP4K4 significantly repressed pancreatic cancer cell growth.
      Therefore, we conclude that miR-141 targets MAP4K4, acts as a tumor suppressor in
      pancreatic cancer cells, and may serve as a novel therapeutic agent for miRNA
      based pancreatic cancer therapy.

PMID- 24013098
TI  - Analysis of the quantity and quality of published randomised controlled trials
      related to injury prevention from 2001 to 2010 in China.
AB  - OBJECTIVE: To report the quantity and quality of published randomised controlled
      trails (RCT) on injury prevention in China. DESIGN: Bibliometric analysis.
      SETTING: China, 2001-2010. DATA SOURCES: The published RCTs that were indexed by
      four domestic electronic databases and two international databases between 1
      January 2001 and 31 December 2010. MAIN OUTCOME MEASURES: Numbers and proportions
      of published RCTs and those that did not report or specify the quality items
      recommended by Cochrane Handbook for Systematic Reviews of Intervention V.5.0.0.
      RESULTS: Of 4834 publications of injury prevention, 25 RCTs with 55,431
      participants were identified. One study had no full text. Twenty-three RCTs were
      published in Chinese language. All 25 studies chose education as the
      intervention, including 19 studies using education as single intervention and 6
      studies using education as a part of combined intervention. Eighteen of 19
      studies that used injury incidence rate as the primary outcome measure; 10
      studies reported 24-59% reductions in injury incidence rate in the intervention
      group, and 8 studies reported 24-76% rate difference between the intervention
      group and the control group after the implementation of intervention. Only 1
      study reported no significant difference. The other 6 studies only reported
      improvements in knowledge, attitude and practice/behaviour. None of 24 studies
      with full text included the information of 'allocation concealment', 'blinding'
      and 'free of early stopping bias'. CONCLUSIONS: The value of 25 published RCTs
      cannot be determined due to the lack of quality information. More high-quality
      RCTs need to be performed in the future.

PMID- 24013099
TI  - Combined deletion of two Condensin II system genes (NCAPG2 and MCPH1) in a case
      of severe microcephaly and mental deficiency.
AB  - 7qter deletion syndrome includes prenatal and/or postnatal growth retardation,
      microcephaly, psychomotor delay or mental retardation and a characteristic
      dysmorphism. If clinical features are well described, the molecular mechanisms
      underlying the 7qter deletion syndrome remain unknown. Those deletions usually
      arise de novo. Here, we describe a young boy with an abnormal phenotype
      consistent with a 7qter deletion syndrome. High resolution genomic analysis
      (Affymetrix Human Genome Wide SNP 6.0) revealed a 7q36.3 deletion encompassing
      NCAPG2, ESYT2, WDR60 and VIPR2, inherited from his asymptomatic father and
      paternal grandfather. In addition, the patient also harbored a MCPH1 deletion
      inherited from his healthy mother. Combined NCAPG2 and MCPH1 deletions were
      correlated with low mRNA levels and protein expression in the patient. MCPH1 and
      NCAPG2 proteins interaction is known to control chromosome structure and we thus
      propose that double heterozygosity for null mutations of those two genes of the
      Condensin II system contribute to mental deficiency with severe microcephaly
      phenotype. 

PMID- 24013100
TI  - Industrial PE-2 strain of Saccharomyces cerevisiae: from alcoholic fermentation
      to the production of recombinant proteins.
AB  - Saccharomyces cerevisiae is the most important microorganism used in the ethanol
      fermentation process. The PE-2 strain of this yeast is widely used to produce
      alcohol in Brazil due to its high fermentation capacity. The aim of the present
      study was to develop an expression system for recombinant proteins using the
      industrial PE-2 strain of S. cerevisiae during the alcoholic fermentation
      process. The protein chosen as a model for this system was CaneCPI-1, a cysteine
      peptidase inhibitor. A plasmid containing the CaneCPI-1 gene was constructed and
      yeast cells were transformed with the pYADE4_CaneCPI-1 construct. To evaluate the
      effect on fermentation ability, the transformed strain was used in the
      fermentation process with cell recycling. During the nine-hour fermentative
      cycles the transformed strain did not have its viability and fermentation ability
      affected. In the last cycle, when the fermentation lasted longer, the protein was
      expressed probably at the expense of ethanol once the sugars were exhausted. The
      recombinant protein was expressed in yeast cells, purified and submitted to
      assays of activity that demonstrated its functionality. Thus, the industrial PE-2
      strain of S. cerevisiae can be used as a viable system for protein expression and
      to produce alcohol simultaneously. The findings of the present study demonstrate
      the possibility of producing recombinant proteins with biotechnological
      applications during the ethanol fermentation process.

PMID- 24013101
TI  - Relations of hedonic hunger and behavioral change to weight loss among adults in
      a behavioral weight loss program utilizing meal-replacement products.
AB  - Greater self-regulatory behavior usage is associated with greater weight loss
      within behavioral weight loss treatments. Hedonic hunger (i.e., susceptibility to
      environmental food cues) may impede successful behavior change and weight loss.
      Adult men and women (N = 111, body mass index M +/- SD = 35.89 +/- 6.97 kg/m(2))
      were assessed before and after a 15-week lifestyle change weight loss program
      with a partial meal-replacement diet. From pre- to post-treatment, reported
      weight control behavior usage improved and hedonic hunger decreased, and these
      changes were inversely related. Individuals with higher hedonic hunger scores at
      baseline showed the greatest weight loss. Similarly, participants with lower
      baseline use of weight control behaviors lost more weight, and increased weight
      control behavior usage was associated with greater weight loss-particularly among
      individuals with low baseline hedonic hunger. Further study is warranted
      regarding the significance of hedonic hunger in weight loss treatments. 

PMID- 24013102
TI  - Enrichment of target sequences for next-generation sequencing applications in
      research and diagnostics.
AB  - Abstract Targeted re-sequencing such as gene panel sequencing (GPS) has become
      very popular in medical genetics, both for research projects and in diagnostic
      settings. The technical principles of the different enrichment methods have been
      reviewed several times before; however, new enrichment products are constantly
      entering the market, and researchers are often puzzled about the requirement to
      take decisions about long-term commitments, both for the enrichment product and
      the sequencing technology. This review summarizes important considerations for
      the experimental design and provides helpful recommendations in choosing the best
      sequencing strategy for various research projects and diagnostic applications. 

PMID- 24013103
TI  - Cancer antigen 125, human epididymis 4, kallikrein 6, osteopontin and soluble
      mesothelin-related peptide immunocomplexed with immunoglobulin M in epithelial
      ovarian cancer diagnosis.
AB  - BACKGROUND: Human epididymis protein 4 (HE4), kallikrein 6 (KLK6), osteopontin
      (OPN) and soluble mesothelin-related peptide (SMRP) are new promising biomarkers
      that could integrate CA125 in epithelial ovarian cancer (EOC) diagnosis. The
      autoantibody response to tumor antigens is a potential tool for improving the
      diagnostic performances of biomarkers. The aim of this study was to assess the
      diagnostic potential of these biomarkers in the form of free markers and
      immunocomplexed with immunoglobulin M (IgM). Moreover, we analyzed the
      association between these markers and clinico-pathological characteristics of EOC
      patients. METHODS: Serum and plasma samples of 60 healthy controls, 60 ovarian
      benign cysts, 60 endometriosis and 60 EOCs, collected before any treatment, were
      tested for CICs and free antigens by immunoassays. RESULTS: Immunocomplexes were
      characterized by poor sensitivity and specificity, since they allowed the
      detection only of a small number of EOC patients and were increased in patients
      with benign gynecological pathologies. However, the markers in the form of free
      antigens showed good diagnostic performances. Of note, CA125 and HE4 showed high
      sensitivity in the detection of the malignancy and HE4 emerged as a useful
      biomarker in differential diagnosis between EOC and endometriosis. Finally,
      elevated KLK6 and OPN, were associated with advanced FIGO stage, high grade
      disease, suboptimally debulked tumor and ascites. CONCLUSIONS: This study
      confirms the diagnostic role of CA125, HE4, KLK6, OPN and SMRP, and for the first
      time showed that CA125, HE4, KLK6, OPN and SMRP immunocomplexed with IgM are not
      a potential tool for EOC diagnosis.

PMID- 24013104
TI  - Five years later: are accelerated, second-degree program graduates still in the
      workforce?
AB  - This retrospective study explores the work activities of graduates from an
      accelerated, second-degree BSN program. There is documented growth in the number
      of accelerated, second-degree programs and the number of graduates from these
      programs. However, there are no published studies of whether or not these
      graduates are members of the workforce 5 years following graduation. This
      retrospective study found that the majority of the graduates are employed in
      nursing, and a large percentage have earned or are pursuing advanced degrees in
      nursing.

PMID- 24013106
TI  - Bidirectional best hits miss many orthologs in duplication-rich clades such as
      plants and animals.
AB  - Bidirectional best hits (BBH), which entails identifying the pairs of genes in
      two different genomes that are more similar to each other than either is to any
      other gene in the other genome, is a simple and widely used method to infer
      orthology. A recent study has analyzed the link between BBH and orthology in
      bacteria and archaea and concluded that, given the very high consistency in BBH
      they observed among triplets of neighboring genes, a high proportion of BBH are
      likely to be bona fide orthologs. However, limited by their analysis setup, the
      previous study could not easily test the reverse question: which proportion of
      orthologs are BBH? In this follow-up study, we consider this question in theory
      and answer it based on conceptual arguments, simulated data, and real biological
      data from all three domains of life. Our analyses corroborate the findings of the
      previous study, but also show that because of the high rate of gene duplication
      in plants and animals, as much as 60% of orthologous relations are missed by the
      BBH criterion. 

PMID- 24013105
TI  - Lizards and LINEs: selection and demography affect the fate of L1
      retrotransposons in the genome of the green anole (Anolis carolinensis).
AB  - Autonomous retrotransposons lacking long terminal repeats (LTR) account for much
      of the variation in genome size and structure among vertebrates. Mammalian
      genomes contain hundreds of thousands of non-LTR retrotransposon copies, mostly
      resulting from the amplification of a single clade known as L1. The genomes of
      teleost fish and squamate reptiles contain a much more diverse array of non-LTR
      retrotransposon families, whereas copy number is relatively low. The majority of
      non-LTR retrotransposon insertions in nonmammalian vertebrates also appear to be
      very recent, suggesting strong purifying selection limits the accumulation of non
      LTR retrotransposon copies. It is however unclear whether this turnover model,
      originally proposed in Drosophila, applies to nonmammalian vertebrates. Here, we
      studied the population dynamics of L1 in the green anole lizard (Anolis
      carolinensis). We found that although most L1 elements are recent in this genome,
      truncated insertions accumulate readily, and many are fixed at both the
      population and species level. In contrast, full-length L1 insertions are found at
      lower population frequencies, suggesting that the turnover model only applies to
      longer L1 elements in Anolis. We also found that full-length L1 inserts are more
      likely to be fixed in populations of small effective size, suggesting that the
      strength of purifying selection against deleterious alleles is highly dependent
      on host demographic history. Similar mechanisms seem to be controlling the fate
      of non-LTR retrotransposons in both Anolis and teleostean fish, which suggests
      that mammals have considerably diverged from the ancestral vertebrate in terms of
      how they interact with their intragenomic parasites.

PMID- 24013107
TI  - Medical and endoscopic therapies for angiodysplasia and gastric antral vascular
      ectasia: a systematic review.
AB  - BACKGROUND & AIMS: Few studies have compared the efficacy and complications of
      endoscopic or medical therapies for bleeding angiodysplasias or gastric antral
      vascular ectasias (GAVE). We conducted a systematic review to evaluate therapies.
      METHODS: We performed a PubMed search for studies (written in English from
      January 1, 1980, through January 1, 2013) of medical or endoscopic treatment of
      bleeding angiodysplasias and GAVE. Measured outcomes included levels of
      hemoglobin, transfusion requirements, rebleeding rates, complications, treatment
      failures, and overall mortality. RESULTS: We analyzed data from 63 studies that
      met inclusion criteria; 50 evaluated endoscopic treatment (1790 patients), 13
      evaluated medical treatment (392 patients), and 12 were comparative studies. In
      patients with angiodysplasias, the combination of estrogen and progesterone did
      not significantly reduce bleeding episodes, compared with placebo (0.7/y vs
      0.9/y, respectively), and increased mortality, compared with conservative therapy
      (33% vs 21%). A higher percentage of patients receiving octreotide were free of
      rebleeding at 1 and 2 years vs placebo (77% vs 55% and 68% vs 36%, respectively;
      P = .03). Thalidomide reduced the number of bleeding episodes (-8.96/y), compared
      with iron therapy (-1.38/y, P < .01), but neither treatment reduced mortality.
      More patients with GAVE treated by endoscopic band ligation were free from
      rebleeding (92%) than those treated with argon plasma coagulation (32%, P = .01).
      CONCLUSIONS: In a systematic review, we found a low quality of evidence to
      support treatment of angiodysplasias with thalidomide or the combination of
      estrogen and progesterone and insufficient evidence to support treatment with
      octreotide. There is also insufficient evidence for endoscopic therapy of
      angiodysplasia or GAVE. Well-designed randomized controlled trials are needed to
      study the efficacy and complications of medical and endoscopic treatments for
      patients with angiodysplasias or GAVE.

PMID- 24013108
TI  - Cholestatic phenotypes of autoimmune hepatitis.
AB  - Autoimmune hepatitis can have cholestatic features that are outside the codified
      diagnostic criteria. These features have uncertain effects on the clinical
      presentation and progression of disease. Patients with autoimmune hepatitis can
      have antimitochondrial antibodies and coincidental bile duct injury or loss (2%
      13% of patients), focal biliary strictures and dilations based on cholangiography
      (2%-11%), or histologic changes of bile duct injury or loss in the absence of
      other features (5%-11%). These findings probably represent atypical
      manifestations of autoimmune hepatitis or variants of primary biliary cirrhosis
      or primary sclerosing cholangitis, depending on the predominant findings. Serum
      levels of alkaline phosphatase and gamma-glutamyl transferase, histologic
      features of bile duct injury, and findings from cholangiography are associated
      with responsiveness to corticosteroid therapy and individualized alternative
      treatments. Corticosteroid therapy, in combination with low-dose ursodeoxycholic
      acid, has been promulgated by international societies, but these recommendations
      are not based on strong evidence. The frequency, variable outcomes, and
      uncertainties in diagnosis and management of the cholestatic phenotypes must be
      addressed by a collaborative investigational network. This network should define
      the genetic and pathologic features of these disorders, standardize their
      nomenclature, and establish a treatment algorithm. In this review, the different
      cholestatic phenotypes of autoimmune hepatitis, mechanisms of pathogenesis,
      current management strategies and outcomes, and opportunities for improving
      understanding and therapy are presented. 

PMID- 24013109
TI  - Epstein-Barr virus-associated smooth muscle tumours after transplantation,
      infection with human immunodeficiency virus and congenital immunodeficiency
      syndromes.
AB  - Smooth muscle tumours (SMT) after transplantation (PTSMT) or associated with
      congenital immunodeficiency syndromes (CI-SMT) and human immunodeficiency virus
      (HIV-SMT) are rare. The majority of PTSMT and CI-SMT are associated with Epstein
      Barr virus (EBV), while some HIV-SMT can be EBV-negative. SMT in immunodeficient
      states may present with unspecific symptoms which are mainly related to tumour
      localisation. In PTSMT, >50% of tumours manifest in the liver/transplant liver,
      but in general PTSMT, HIV-SMT and CI-SMT can occur at any site as single or
      multiple tumours. Multiple tumour manifestations do not define metastatic disease
      as PTSMT can occur synchronously and/or metachronously. PTSMT can originate from
      the recipient as well as from the donor. Morphologically, most tumours, in
      particular PTSMT, lack marked histological atypia or tumour necrosis, while some
      HIV-SMT and CI-SMT can present as sarcoma-like variants, but histomorphology does
      not predict clinical aggressiveness or tumourbiological behaviour. In PTSMT,
      surgery and reduced immunosuppression show comparable overall survival rates,
      while poor prognosis is mainly associated with intracranial manifestation and non
      resectable tumours. In HIV-SMT and CI-SMT, surgery should be performed. In all 3
      tumour types, adverse prognosis is mainly related to comorbidities associated
      with immunosuppression but not with the extent of histological atypia or tumour
      size. 

PMID- 24013110
TI  - Crosswalk time estimation and time perception: an experimental study among older
      female pedestrians.
AB  - Since the sense of time is strongly influenced by advancing age, this laboratory
      study aimed to find out more about older pedestrians' decisions to cross the
      road, focusing on their estimates of how long it would take them to cross. The
      walking times of older female adults with or without any walking impairment and
      of healthy young adults were recorded on a walkway representing a road section.
      Participants also performed actual and imagined crossings of this "road" as well
      as a duration production task. Results showed that misestimated crossing times
      were related to the individual time base, with stronger time distortions in some
      older participants. A comparison between the older participants with disabilities
      and their age-paired counterparts without disabilities revealed an overestimation
      of crossing time in the former, affording them a bigger safety margin. 

PMID- 24013111
TI  - The "killing zone" revisited: serial nonlinearities predict general aviation
      accident rates from pilot total flight hours.
AB  - BACKGROUND: Is there a "killing zone" (Craig, 2001)-a range of pilot flight time
      over which general aviation (GA) pilots are at greatest risk? More broadly, can
      we predict accident rates, given a pilot's total flight hours (TFH)? These
      questions interest pilots, aviation policy makers, insurance underwriters, and
      researchers alike. Most GA research studies implicitly assume that accident rates
      are linearly related to TFH, but that relation may actually be multiply
      nonlinear. This work explores the ability of serial nonlinear modeling functions
      to predict GA accident rates from noisy rate data binned by TFH. METHOD: Two sets
      of National Transportation Safety Board (NTSB)/Federal Aviation Administration
      (FAA) data were log-transformed, then curve-fit to a gamma-pdf-based function.
      Despite high rate-noise, this produced weighted goodness-of-fit (Rw(2)) estimates
      of .654 and .775 for non-instrument-rated (non-IR) and instrument-rated pilots
      (IR) respectively. CONCLUSION: Serial-nonlinear models could be useful to
      directly predict GA accident rates from TFH, and as an independent variable or
      covariate to control for flight risk during data analysis. Applied to FAA data,
      these models imply that the "killing zone" may be broader than imagined.
      Relatively high risk for an individual pilot may extend well beyond the 2000-h
      mark before leveling off to a baseline rate.

PMID- 24013112
TI  - Can a safety-in-numbers effect and a hazard-in-numbers effect co-exist in the
      same data?
AB  - Safety-in-numbers denotes a non-linear relationship between exposure (traffic
      volume) and the number of accidents, characterised by declining risk as traffic
      volume increases. There is safety-in-numbers when the number of accidents
      increases less than proportional to traffic volume, e.g. a doubling of traffic
      volume is associated with less than a doubling of the number of accidents. Hazard
      in-numbers, a less-used concept, refers to the opposite effect: the number of
      accidents increases more than in proportion to traffic volume, e.g. is more than
      doubled when traffic volume is doubled. This paper discusses whether a safety-in
      numbers effect and a hazard-in-numbers effect can co-exist in the same data. It
      is concluded that both effects can exist in a given data set. The paper proposes
      to make a distinction between partial safety-in-numbers and complete safety-in
      numbers. Another issue that has been raised in discussions about the safety-in
      numbers effect is whether the effect found in some studies is an artefact created
      by the way exposure was measured. The paper discusses whether measuring exposure
      as a rate or a share, e.g. kilometres travelled per inhabitant per year, will
      generate a safety-in-numbers effect as a statistical artefact. It is concluded
      that this is the case. The preferred measure of exposure is a count of the number
      of road users. The count should not be converted to a rate or to the share any
      group of road user contribute to total traffic volume. 

PMID- 24013113
TI  - Vibrational spectroscopy of the borate mineral pinnoite MgB2O(OH)6.
AB  - There is a large number of boron containing minerals with water and/or hydroxyl
      units of which pinnoite MgB2O(OH)6 is one. Some discussion about the molecular
      structure of pinnoite exists in the literature. Whether water is involved in the
      structure is ill-determined. The molecular structure of pinnoite has been
      assessed by the combination of Raman and infrared spectroscopy. The Raman
      spectrum is characterized by an intense band at 900 cm(-1) assigned to the BO
      stretching vibrational mode. A series of bands in the 1000-1320 cm(-1) spectral
      range are attributed to BO antisymmetric stretching modes and in-plane bending
      modes. The infrared spectrum shows complexity in this spectral range. Multiple
      Raman OH stretching vibrations are found at 3179, 3399, 3554 and 3579 cm(-1). The
      infrared spectrum shows a series of overlapping bands with bands identified at
      3123, 3202, 3299, 3414, 3513 and 3594 cm(-1). By using a Libowitzky type
      function, hydrogen bond distances were calculated. Two types of hydrogen bonds
      were identified based upon the hydrogen bond distance. It is important to
      understand the structure of pinnoite in order to form nanomaterials based upon
      the pinnoite structure.

PMID- 24013114
TI  - Comprehensive physicochemical studies of a new hybrid material: 2-amino-4-methyl
      3-nitropyridinium hydrogen oxalate.
AB  - A new organic-organic salt, 2-amino-4-methyl-3-nitropyridinium hydrogen oxalate
      (AMNPO), and its deuterium analogue have been synthesized and characterized by
      means of FT-IR, FT-Raman, DSC and single crystal X-ray studies. The DSC
      measurements and temperature dependence of the IR and Raman spectra in the range
      4-295 K show that it undergoes a reversible phase transition at ~240 K. At room
      temperature it crystallizes in noncentrosymmetric space group P21. The unit-cell
      is built of the 2-amino-4-methyl-3-nitropyridinium cations and oxalate monoanions
      which are connected via the N-H...O and O-H...O hydrogen bonds. The geometrical
      and hydrogen bond parameters are similar for non-deuterated (at 120 and 293 K)
      and deuterated compounds (at 90K). The phase transition is probably a consequence
      of order-disorder transition inside of hydrogen network. The 6-311G(2d,2p) basis
      set with B3LYP functional have been used to discuss the structure and vibrational
      spectra of the studied compound.

PMID- 24013115
TI  - A variational algebraic method used to study the full vibrational spectra and
      dissociation energies of some specific diatomic systems.
AB  - The algebraic method (AM) proposed by Sun et al. is improved to be a variational
      AM (VAM) to offset the possible experimental errors and to adapt to the
      individual energy expansion nature of different molecular systems. The VAM is
      used to study the full vibrational spectra {Eupsilon} and the dissociation
      energies De of (4)HeH(+)-X(1)Sigma(+), (7)Li2-1(3)Deltag,Na2-C(1)Piu,NaK-7(1)Pi,
      Cs2-B(1)Piu and (79)Br2-beta1g((3)P2) diatomic electronic states. The results not
      only precisely reproduce all known experimental vibrational energies, but also
      predict correct dissociation energies and all unknown high-lying levels that may
      not be given by the original AM or other numerical methods or experimental
      methods. The analyses and the skill suggested here might be useful for other
      numerical simulations and theoretical fittings using known data that may carry
      inevitable errors.

PMID- 24013116
TI  - Building national M&E systems in the context of changing aid modalities: the
      underexplored potential of national evaluation societies.
AB  - Changes in the aid architecture have provided a renewed impetus for monitoring
      and evaluation (M&E), while simultaneously imposing a major reform agenda on the
      key players involved. More specifically, since 1999, aid-dependent countries have
      been facing pressure to strengthen their national M&E systems, while donors have
      been asked to refrain from using their own parallel systems and to rely instead
      on country systems. Surprisingly, attempts to strengthen national M&E frameworks
      have thus far largely overlooked the potential of national evaluation societies
      (NES). Similarly, NES have also remained off the academic radar. Our study aims
      to fill this gap by mapping key features of NES, as well as their perceived
      contributions to country-led M&E. In this effort, we rely upon evidence from our
      survey of 23 NES in Sub-Saharan African countries with Poverty Reduction Strategy
      Papers (PSRP). Our findings show that there is quite some diversity among NES.
      Overall, NES are active organisations, whose unique membership features a wide
      variety of national M&E stakeholders who potentially play key roles in country
      led and localised M&E development. Major obstacles faced by NES include the lack
      of financial resources, donor support and political influence. Survey findings
      also demonstrate that the increasing interest of donors and governments in NES
      has yet to materialise into strategic support. 

PMID- 24013117
TI  - Gene promoters dictate histone occupancy within genes.
AB  - Spt6 is a transcriptional elongation factor and histone chaperone that
      reassembles transcribed chromatin. Genome-wide H3 mapping showed that Spt6
      preferentially maintains nucleosomes within the first 500 bases of genes and
      helps define nucleosome-depleted regions in 5' and 3' flanking sequences. In Spt6
      depleted cells, H3 loss at 5' ends correlates with reduced pol II density
      suggesting enhanced transcription elongation. Consistent with its 'Suppressor of
      Ty' (Spt) phenotype, Spt6 inactivation caused localized H3 eviction over 1-2
      nucleosomes at 5' ends of Ty elements. H3 displacement differed between genes
      driven by promoters with 'open'/DPN and 'closed'/OPN chromatin conformations with
      similar pol II densities. More eviction occurred on genes with 'closed'
      promoters, associated with 'noisy' transcription. Moreover, swapping of 'open'
      and 'closed' promoters showed that they can specify distinct downstream patterns
      of histone eviction/deposition. These observations suggest a novel function for
      promoters in dictating histone dynamics within genes possibly through effects on
      transcriptional bursting or elongation rate. 

PMID- 24013119
TI  - Autophagy plays a WASHing game.

PMID- 24013118
TI  - FoxO3 coordinates metabolic pathways to maintain redox balance in neural stem
      cells.
AB  - Forkhead Box O (FoxO) transcription factors act in adult stem cells to preserve
      their regenerative potential. Previously, we reported that FoxO maintains the
      long-term proliferative capacity of neural stem/progenitor cells (NPCs), and that
      this occurs, in part, through the maintenance of redox homeostasis. Herein, we
      demonstrate that among the FoxO3-regulated genes in NPCs are a host of enzymes in
      central carbon metabolism that act to combat reactive oxygen species (ROS) by
      directing the flow of glucose and glutamine carbon into defined metabolic
      pathways. Characterization of the metabolic circuit observed upon loss of FoxO3
      revealed a drop in glutaminolysis and filling of the tricarboxylic acid (TCA)
      cycle. Additionally, we found that glucose uptake, glucose metabolism and
      oxidative pentose phosphate pathway activity were similarly repressed in the
      absence of FoxO3. Finally, we demonstrate that impaired glucose and glutamine
      metabolism compromises the proliferative potential of NPCs and that this is
      exacerbated following FoxO3 loss. Collectively, our findings show that a FoxO3
      dependent metabolic programme supports redox balance and the neurogenic potential
      of NPCs. 

PMID- 24013120
TI  - The NAD-dependent deacetylase sirtuin 2 is a suppressor of microglial activation
      and brain inflammation.
AB  - Deleterious sustained inflammation mediated by activated microglia is common to
      most of neurologic disorders. Here, we identified sirtuin 2 (SIRT2), an abundant
      deacetylase in the brain, as a major inhibitor of microglia-mediated inflammation
      and neurotoxicity. SIRT2-deficient mice (SIRT2(-/-)) showed morphological changes
      in microglia and an increase in pro-inflammatory cytokines upon intracortical
      injection of lipopolysaccharide (LPS). This response was associated with
      increased nitrotyrosination and neuronal cell death. Interestingly, manipulation
      of SIRT2 levels in microglia determined the response to Toll-like receptor (TLR)
      activation. SIRT2 overexpression inhibited microglia activation in a process
      dependent on serine 331 (S331) phosphorylation. Conversely, reduction of SIRT2 in
      microglia dramatically increased the expression of inflammatory markers, the
      production of free radicals, and neurotoxicity. Consistent with increased NF
      kappaB-dependent transcription of inflammatory genes, NF-kappaB was found
      hyperacetylated in the absence of SIRT2, and became hypoacetylated in the
      presence of S331A mutant SIRT2. This finding indicates that SIRT2 functions as a
      'gatekeeper', preventing excessive microglial activation through NF-kappaB
      deacetylation. Our data uncover a novel role for SIRT2 opening new perspectives
      for therapeutic intervention in neuroinflammatory disorders. 

PMID- 24013122
TI  - Combined application of dispersive liquid-liquid microextraction based on the
      solidification of floating organic droplets and charged aerosol detection for the
      simple and sensitive quantification of macrolide antibiotics in human urine.
AB  - A novel analytical method combining dispersive liquid-liquid microextraction
      based on the solidification of floating organic droplets (DLLME-SFO) and liquid
      chromatography with charged aerosol detection (LC-CAD) was established. For the
      first time, CAD was applied for the detection of macrolide antibiotics lacking
      chromophores. Parameters influencing the microextraction efficiency were
      systematically investigated, and the optimized microextraction conditions yielded
      high enrichment factors in the range of 60-106. The combined application of DLLME
      SFO and LC-CAD provided the sensitivity of the method, expressed as the limit of
      detection (LOD), as low as 10 to 40ngmL(-1) and intra-day and inter-day
      precisions below 8.7% and 12.6%, respectively. The measured absolute recovery
      values were approximately 100%, indicating that the extraction efficiency was
      very high. Direct comparisons of the liquid-liquid extraction and organic solvent
      precipitation methods demonstrated that the proposed method was more sensitive,
      specific, rapid, and environmentally friendly for the determination of five
      macrolide antibiotics in human urine. The results suggest that the combined use
      of DLLME-SFO and LC-CAD may be applicable to the analysis of various compounds
      with poor to no chromophores in complex matrices. 

PMID- 24013121
TI  - Determination of intracellular fludarabine triphosphate in human peripheral blood
      mononuclear cells by LC-MS/MS.
AB  - Fludarabine is a nucleoside analog routinely used in conditioning regimens of
      pediatric allogeneic stem cell transplantation to promote stem cell engraftment.
      In children, it remains a challenge to accurately and precisely quantify the
      active intracellular triphosphate species of fludarabine in vivo, primarily due
      to limitations on blood volume and inadequate assay sensitivity. Here we report a
      liquid chromatography tandem mass spectrometry (LC-MS/MS) method for
      determination of fludarabine triphosphate in human peripheral blood mononuclear
      cells (PBMC). PBMC (~5 million cells) were collected and lysed in 1mL 70%
      methanol containing 1.2mM tris buffer (pH 7.4). The lysate (80MUL) was mixed with
      internal standard (2-chloro-adenosine triphosphate, 150ng/mL, 20MUL) and injected
      onto an API5000 LC-MS/MS system. Separation was achieved on a hypercarb column
      (100mm*2.1mm, 3MUm) eluted with 100mM ammonium acetate (pH 9.8) and acetonitrile
      in a gradient mode at a flow rate of 0.4mL/min. Multiple reactions monitoring
      (MRM) and electrospray ionization in negative mode (ESI(-)) were used for
      detection. The ion pairs 524.0/158.6 for the drug and 540.0/158.8 for the IS were
      selected for quantification and 524.0/425.7 used for confirmation. Retention time
      was 3.0 and 3.4min for fludarabine triphosphate and the IS, respectively. The
      concentration range for the calibration curve was 1.52-76nM. Our method is
      simple, fast, and has been successfully applied in a clinical dose-concentration
      study in children to quantify intracellular fludarabine in low volume clinical
      samples. The median concentration was 1.03 and 3.19pmole/million PBMC at trough
      and peak time points, respectively. Fludarabine triphosphate is degraded in water
      within hours but relatively stable in 70% methanol-tris (1.2mM, pH 7.4). One
      limitation is that the hypercarb column takes a longer time to equilibrate than
      conventional reverse phase columns, and peaks become broad and distorted if the
      column is not washed and stored properly. 

PMID- 24013123
TI  - Aryl hydrocarbon receptor-dependent cell cycle arrest in isolated mouse oval
      cells.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor,
      which mediates toxic responses to environmental pollutants, such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Besides its well known
      role in induction of xenobiotic metabolizing enzymes, for instance CYP1A1, the
      AhR is also involved in tumor promotion in rodents although the underlying
      mechanisms are still poorly understood. Additionally, the AhR is known to
      regulate cellular proliferation, which might result in either inhibition or
      stimulation of proliferation depending on the cell-type studied. Potential
      targets in hepatocarcinogenesis are liver oval (stem/progenitor) cells. In the
      present work we analyzed the effect of TCDD on proliferation in oval cells
      derived from mouse liver. We show that TCDD inhibits proliferation in these
      cells. In line, the amount of G0/G1 cells increases in response to TCDD. We
      further show that the expression of cyclin D1 and cyclin A is decreased, while
      p27 is increased. As a result, the retinoblastoma protein is not phosphorylated
      thereby inducing G0/G1 arrest. Pharmacological inhibition of the AhR and knock
      down of AhR expression by RNA interference decreased the inhibitory effect on
      cell cycle and protein expression, indicating that the AhR at least partially
      mediates cell cycle arrest. 

PMID- 24013124
TI  - Improving the efficiency of quantitative (1)H NMR: an innovative external
      standard-internal reference approach.
AB  - The classical internal standard quantitative NMR (qNMR) method determines the
      purity of an analyte by the determination of a solution containing the analyte
      and a standard. Therefore, the standard must meet the requirements of chemical
      compatibility and lack of resonance interference with the analyte as well as a
      known purity. The identification of such a standard can be time consuming and
      must be repeated for each analyte. In contrast, the external standard qNMR method
      utilizes a standard with a known purity to calibrate the NMR instrument. The
      external standard and the analyte are measured separately, thereby eliminating
      the matter of chemical compatibility and resonance interference between the
      standard and the analyte. However, the instrumental factors, including the
      quality of NMR tubes, must be kept the same. Any deviations will compromise the
      accuracy of the results. An innovative qNMR method reported herein utilizes an
      internal reference substance along with an external standard to assume the role
      of the standard used in the traditional internal standard qNMR method. In this
      new method, the internal reference substance must only be chemically compatible
      and be free of resonance-interference with the analyte or external standard
      whereas the external standard must only be of a known purity. The exact purity or
      concentration of the internal reference substance is not required as long as the
      same quantity is added to the external standard and the analyte. The new method
      reduces the burden of searching for an appropriate standard for each analyte
      significantly. Therefore the efficiency of the qNMR purity assay increases while
      the precision of the internal standard method is retained. 

PMID- 24013125
TI  - 2-Methyltetrahydrofuran and cyclopentylmethylether: two green solvents for
      efficient purification of membrane proteins like FhuA.
AB  - beta-Barrel shaped membrane proteins are attractive hosts for hybrid catalysts in
      which reactions are controlled through space. Production and extraction of beta
      barrel shaped membrane proteins in gram scale is challenging due to their
      hydrophobicity. Solvent mixtures such as chloroform/methanol (CM) are widely used
      for membrane protein extraction but toxicity and mutagenicity were reported in
      several cases. 2-Methyltetrahydrofuran (2-MeTHF) and cyclopentylmethylether
      (CPME) are two green (reduction of solvent-related environmental damage in
      chemical production) and potentially efficient solvents for membrane protein
      purification. On the example of the ferric hydroxamate uptake protein component A
      (FhuA) a 4-Step method was developed to provide gram amounts of highly purified
      FhuA: cell disruption (Step 1), removal of membrane protein impurities with n
      octyl-poly-oxyethylene (oPOE) (Step 2), dissolution of membranes and FhuA
      precipitation (Step 3), and refolding using urea and dialysis with polyethylene
      polyethyleneglycol (PE-PEG; Step 4) resulted in high FhuA purity (95% 2-MeTHF,
      80% CPME; 70mg FhuA per liter fermenter broth). Structural integrity of FhuA
      protein was confirmed by circular dichroism (CD) and a translocation
      functionality assay. 

PMID- 24013126
TI  - Rapid separation and quantitation of curcuminoids combining pseudo two
      dimensional liquid flash chromatography and NMR spectroscopy.
AB  - Rapid separation, characterization and quantitation of curcuminoids are important
      owing to their numerous pharmacological properties including antimicrobial,
      antiviral, antifungal, anticancer, and anti-inflammatory activities. In the
      present study, pseudo two-dimensional liquid flash chromatography was used for
      the separation of four curcuminoids (curcumin, demethoxy curcumin, bisdemethoxy
      curcumin and dihydro bisdemethoxy curcumin) for the first time. Silica and diol
      columns were used for separation of curcuminoids using gradient mobile phase. The
      separated peaks were monitored at 244, 360nm to obtain four compounds. The purity
      of compounds were determined by rapid quantitative (1)H NMR (qNMR) using 3
      (trimethylsilyl) propionic-(2,2,3,3-d4) acid sodium salt (TSP-d4) (0.012%) in
      D2O. These results were compared with those obtained by HPLC method. The purity
      of isolated curcuminoids using pseudo 2D chromatography was found to be in the
      range of 92.4-95.45%. The structures of these compounds were characterized
      unambiguously using (13)C (APT) NMR spectra. The developed pseudo 2D separation
      technique has the advantage of simplified automation with shorter run time
      compared to conventional separation techniques. The method that combines rapid
      pseudo 2D separation and simple quantitation using qNMR reported herein can be of
      wide utility for routine analysis of curcuminoids in complex mixtures. 

PMID- 24013127
TI  - A validated assay for the simultaneous quantification of six tyrosine kinase
      inhibitors and two active metabolites in human serum using liquid chromatography
      coupled with tandem mass spectrometry.
AB  - A sensitive, sophisticated and practical bioanalytical assay for the simultaneous
      determination of six tyrosine kinase inhibitors (imatinib, sunitinib, nilotinib,
      dasatinib, pazopanib, regorafenib) and two active metabolites (N-desmethyl
      imatinib and N-desethyl sunitinib) was developed and validated. For the
      quantitative assay, a mixture of three stable isotopes as internal standards was
      added to human serum, standards and controls. Thereafter, samples were pre
      treated using protein precipitation with methanol. The supernatant was diluted
      with water and injected into an ultra pressure liquid chromatographic system with
      an Acquity TQ tandem mass spectrometry detector. The compounds were separated on
      an Acquity BEH C18 analytical column (100mm*2.1mm ID, 1.7MUm particle size) and
      eluted with a linear gradient system. The ions were detected in the multiple
      reaction monitoring mode. The lower limit of quantification and the linearity of
      all compounds generously met with the concentrations that are to be expected in
      clinical practice. The developed bioanalytical assay can be used for guiding TKI
      therapy in daily clinical practice as well as for investigator-initiated
      research. 

PMID- 24013128
TI  - Analysis of the STAT3 interactome using in-situ biotinylation and SILAC.
AB  - Signal transducer and activator of transcription 3 (STAT3) is activated by a
      variety of cytokines and growth factors. To generate a comprehensive data set of
      proteins interacting specifically with STAT3, we applied stable isotope labeling
      with amino acids in cell culture (SILAC). For high-affinity pull-down using
      streptavidin, we fused STAT3 with a short peptide tag allowing biotinylation in
      situ (bio-tag), which did not affect STAT3 functions. By this approach, 3642
      coprecipitated proteins were detected in human embryonic kidney-293 cells.
      Filtering using statistical and functional criteria finally extracted 136
      proteins as putative interaction partners of STAT3. Both, a physical interaction
      network analysis and the enrichment of known and predicted interaction partners
      suggested that our filtering criteria successfully enriched true STAT3
      interactors. Our approach identified numerous novel interactors, including ones
      previously predicted to associate with STAT3. By reciprocal coprecipitation, we
      were able to verify the physical association between STAT3 and selected
      interactors, including the novel interaction with TOX4, a member of the TOX high
      mobility group box family. Applying the same method, we next investigated the
      activation-dependency of the STAT3 interactome. Again, we identified both known
      and novel interactions. Thus, our approach allows to study protein-protein
      interaction effectively and comprehensively. BIOLOGICAL SIGNIFICANCE: The
      location, activity, function, degradation, and synthesis of proteins are
      significantly regulated by interactions of proteins with other proteins,
      biopolymers and small molecules. Thus, the comprehensive characterization of
      interactions of proteins in a given proteome is the next milestone on the path to
      understanding the biochemistry of the cell. In order to generate a comprehensive
      interactome dataset of proteins specifically interacting with a selected bait
      protein, we fused our bait protein STAT3 with a short peptide tag allowing
      biotinylation in situ (bio-tag). This bio-tag allows an affinity pull-down using
      streptavidin but affected neither the activation of STAT3 by tyrosine
      phosphorylation nor its transactivating potential. We combined SILAC for accurate
      relative protein quantification, subcellular fractionation to increase the
      coverage of interacting proteins, high-affinity pull-down and a stringent
      filtering method to successfully analyze the interactome of STAT3. With our
      approach we confirmed several already known and identified numerous novel STAT3
      interactors. The approach applied provides a rapid and effective method, which is
      broadly applicable for studying protein-protein interactions and their dependency
      on post-translational modifications.

PMID- 24013129
TI  - Isolation and analysis of linker histones across cellular compartments.
AB  - Analysis of histones, especially histone H1, is severely limited by immunological
      reagent availability. This paper describes the application of cellular
      fractionation with LC-MS for profiling histones in the cytosol and upon
      chromatin. First, we show that linker histones enriched by cellular fractionation
      gives less nuclear contamination and higher histone content than when prepared by
      nuclei isolation. Second, we profiled the soluble linker histones throughout the
      cell cycle revealing phosphorylation increases as cells reach mitosis. Finally,
      we monitored histone H1.2-H1.5 translocation to the cytosol in response to the
      CDK inhibitor flavopiridol in primary CLL cells treated ex vivo. Data shows that
      all H1 variants translocate in response to drug treatment with no specific order
      to their cytosolic appearance. The results illustrate the utility of cellular
      fractionation in conjunction with LC-MS for the analysis of histone H1 throughout
      the cell. BIOLOGICAL SIGNIFICANCE: This paper demonstrates the first time
      application of cellular fractionation to characterize cytosolic histone H1 by
      liquid chromatography mass spectrometry (LC-MS). Using the Ramos Burkitt's
      lymphoma cell line, cellular fractionation was shown to give less nuclear
      contamination and higher histone content than preparations by nuclei isolation.
      Further application of the cellular fractionation approach was shown by using
      primary chronic lymphocytic leukemia (CLL) cells to monitor the movement of
      histone H1 across cellular compartments in response to the cyclin dependent
      kinase inhibitor flavopiridol. Collectively, these data establish a mass
      spectrometric method for exploration into the function of cytosolic histone H1.

PMID- 24013130
TI  - Improved working memory performance through self-regulation of dorsal lateral
      prefrontal cortex activation using real-time fMRI.
AB  - Working memory is important for a wide range of high-level cognitive activities.
      Previous studies have shown that the dorsal lateral prefrontal cortex (DLPFC)
      plays a critical role in working memory and that behavioral training of working
      memory can alter the activity of DLPFC. However, it is unclear whether the
      activation in the DLPFC can be self-regulated and whether any self-regulation can
      affect working memory behavior. The recently emerged real-time functional
      magnetic resonance imaging (rtfMRI) technique enables the individuals to acquire
      self-control of localized brain activation, potentially inducing desirable
      behavioral changes. In the present study, we employed the rtfMRI technique to
      train subjects to up-regulate the activation in the left DLPFC, which is linked
      to verbal working memory. After two rtfMRI training sessions, activation in the
      left DLPFC was significantly increased, whereas the control group that received
      sham feedback did not show any increase in DLPFC activation. Pre- and post
      training behavioral tests indicated that performance of the digit span and letter
      memory task was significantly improved in the experimental group. Between-group
      comparison of behavioral changes showed that the increase of digit span in the
      experimental group was significantly greater than that in the control group.
      These findings provide preliminary evidence that working memory performance can
      be improved through learned regulation of activation in associated brain regions
      using rtfMRI. 

PMID- 24013131
TI  - The associations between self-consciousness, depressive state and craving to
      drink among alcohol dependent patients undergoing protracted withdrawal.
AB  - CONTEXT: In order to understand how certain personality traits influence the
      relation between depression symptoms and craving for alcohol, trait self
      consciousness (trait SC) was examined during a withdrawal and detoxification
      program. METHODS: Craving (Obsessive and Compulsive Drinking Scale), depressive
      state (Beck Depression Inventory) and trait SC (Revised Self-Consciousness Scale)
      were assessed in alcohol-dependent inpatients (DSM-IV, N = 30) both at the
      beginning (T1: day 1 or 2) and at the end (T2: day 14 to18) of protracted
      withdrawal during rehabilitation. RESULTS: A significant decrease in craving and
      depressive symptoms was observed from T1 to T2, while SC scores remained stable.
      At both times, strong positive correlations were observed between craving and
      depression. Moreover, regression analyses indicated that trait SC significantly
      moderated the impact of depression on cravings for alcohol. LIMITATIONS: This
      study was performed on a relatively small sample size. Administration of
      medications during detoxification treatment can also be a confounding factor.
      Finally, craving could have been evaluated through other types of measurements.
      CONCLUSIONS: During protracted withdrawal, alcohol craving decreased with the
      same magnitude as depressive mood. Depressive symptoms were related to alcohol
      craving but only among patients with high trait SC scores. Our results suggest
      that metacognitive approaches targeting SC could decrease craving and, in turn,
      prevent future relapses.

PMID- 24013132
TI  - Current-induced skyrmion dynamics in constricted geometries.
AB  - Magnetic skyrmions--vortex-like swirling spin structures with a quantized
      topological number that are observed in chiral magnets--are appealing for
      potential applications in spintronics because it is possible to control their
      motion with ultralow current density. To realize skyrmion-based spintronic
      devices, it is essential to understand skyrmion motions in confined geometries.
      Here we show by micromagnetic simulations that the current-induced motion of
      skyrmions in the presence of geometrical boundaries is very different from that
      in an infinite plane. In a channel of finite width, transverse confinement
      results in steady-state characteristics of the skyrmion velocity as a function of
      current that are similar to those of domain walls in ferromagnets, whereas the
      transient behaviour depends on the initial distance of the skyrmion from the
      boundary. Furthermore, we show that a single skyrmion can be created by an
      electric current in a simple constricted geometry comprising a plate-shaped
      specimen of suitable size and geometry. These findings could guide the design of
      skyrmion-based devices in which skyrmions are used as information carriers.

PMID- 24013133
TI  - Towards control of the size and helicity of skyrmions in helimagnetic alloys by
      spin-orbit coupling.
AB  - Chirality--that is, left- or right-handedness--is an important concept in a broad
      range of scientific areas. In condensed matter, chirality is found not only in
      molecular or crystal forms, but also in magnetic structures. A magnetic skyrmion
      is a topologically stable spin vortex structure, as observed in chiral-lattice
      helimagnets, and is one example of such a structure. The spin swirling direction
      (skyrmion helicity) should be closely related to the underlying lattice chirality
      via the relativistic spin-orbit coupling. Here, we report on the correlation
      between skyrmion helicity and crystal chirality in alloys of helimagnets Mn(1
      x)Fe(x)Ge with varying compositions by Lorentz transmission electron microscopy
      and convergent-beam electron diffraction over a broad range of compositions (x =
      0.3-1.0). The skyrmion lattice constant shows non-monotonous variation with
      composition x, with a divergent behaviour around x = 0.8, where the correlation
      between magnetic helicity and crystal chirality changes sign. This originates
      from continuous variation of the spin-orbit coupling strength and its sign
      reversal in the metallic alloys as a function of x. Controllable spin-orbit
      coupling may offer a promising way to tune skyrmion size and helicity.

PMID- 24013134
TI  - Atrioventricular dyssynchrony provoked diaphragmatic myoclonus.

PMID- 24013135
TI  - Skin cancer in organ transplant recipients.
AB  - Organ transplant recipients (OTR) are at a significantly increased risk for
      developing a wide variety of skin cancers, particularly epithelial skin cancer,
      Merkel cell carcinoma and Kaposi's sarcoma. Melanoma, skin adnexal neoplasm and
      cutaneous lymphomas are also more common in OTR and may differ in their
      clinicopathologic presentation from tumors in immunocompetent patients. The
      accuracy of clinical diagnosis of suspected premalignant and malignant skin
      lesions in OTR is modest. Therefore, histopathological diagnosis is an essential
      element for the diagnostic workup of skin cancers and, in addition, provides
      important information on prognosis. Squamous cell carcinoma and intraepithelial
      neoplasias (actinic keratosis, squamous cell carcinoma in situ or Bowen's
      disease) are the most common forms of skin cancer in OTR. The risk of Merkel cell
      carcinoma and Kaposi's sarcoma is dramatically increased in OTR. Merkel cell
      carcinoma shows a highly aggressive course. Kaposi's sarcoma tends to spread to
      extracutaneous sites. Primary cutaneous lymphomas developing after organ
      transplantation are rare. The spectrum of cutaneous B cell lymphomas in OTR, in
      particular, differs significantly from that of the general population, with a
      predominance of Epstein-Barr virus-driven posttransplant lymphoproliferative
      disorder. This review discusses the clinical and histopathological aspects of
      skin cancers in OTR, the impact of dermatopathological analysis on prognosis and
      the understanding of the pathogenesis of these neoplasms. 

PMID- 24013136
TI  - Human gut microbiota changes reveal the progression of glucose intolerance.
AB  - To explore the relationship of gut microbiota with the development of type 2
      diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on
      their glucose intolerance status: normal glucose tolerance (NGT; n = 44),
      prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gut microbiota
      characterizations were determined with 16S rDNA-based high-throughput sequencing.
      T2DM-related dysbiosis was observed, including the separation of microbial
      communities and a change of alpha diversity between the different glucose
      intolerance statuses. To assess the correlation between metabolic parameters and
      microbiota diversity, clinical characteristics were also measured and a
      significant association between metabolic parameters (FPG, CRP) and gut
      microbiota was found. In addition, a total of 28 operational taxonomic units
      (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most
      of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g.
      Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a
      higher abundance in the NGT group than in the pre-DM group. At genus level, the
      abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre
      DM groups. Previously reported T2DM-related markers were also compared with the
      data in this study, and some inconsistencies were noted. We found that
      Verrucomicrobiae may be a potential marker of T2DM as it had a significantly
      lower abundance in both the pre-DM and T2DM groups. In conclusion, this research
      provides further evidence of the structural modulation of gut microbiota in the
      pathogenesis of diabetes. 

PMID- 24013137
TI  - A novel clinician interface to improve clinician access to up-to-date genetic
      results.
AB  - OBJECTIVES: To understand the impact of GeneInsight Clinic (GIC), a web-based
      tool designed to manage genetic information and facilitate communication of test
      results and variant updates from the laboratory to the clinics, we measured the
      use of GIC and the time it took for new genetic knowledge to be available to
      clinicians. METHODS: Usage data were collected across four study sites for the
      GIC launch and post-GIC implementation time periods. The primary outcome measures
      were the time (average number of days) between variant change approval and
      notification of clinic staff, and the time between notification and viewing the
      patient record. RESULTS: Post-GIC, time between a variant change approval and
      provider notification was shorter than at launch (average days at launch 503.8,
      compared to 4.1 days post-GIC). After e-mail alerts were sent at launch,
      providers clicked into the patient record associated with 91% of these alerts. In
      the post period, clinic providers clicked into the patient record associated with
      95% of the alerts, on average 12 days after the e-mail was sent. DISCUSSION: We
      found that GIC greatly increased the likelihood that a provider would receive
      updated variant information as well as reduced the time associated with
      distributing that variant information, thus providing a more efficient process
      for incorporating new genetic knowledge into clinical care. CONCLUSIONS: Our
      study results demonstrate that health information technology systems have the
      potential effectively to assist providers in utilizing genetic information in
      patient care.

PMID- 24013138
TI  - Limited evidence for effects of intranasal corticosteroids on symptom relief for
      recurrent acute rhinosinusitis.
AB  - OBJECTIVE: To systematically review the evidence base on the effectiveness of
      intranasal corticosteroids in adult patients with recurrent acute rhinosinusitis.
      Data Sources Pubmed, EMBASE, and the Cochrane Library. REVIEW METHODS: A
      comprehensive search was performed up to March 20, 2013. Two reviewers
      independently screened publications on title and abstract. Design of selected
      studies was assessed on directness of evidence and risk of bias. For included
      studies, risk differences with 95% confidence intervals were extracted or
      recalculated. RESULTS: Of 1850 unique records, 3 trials were included. Risk of
      bias was high and directness of evidence was low for 2 trials, the third trial
      had low risk of bias with moderate directness of evidence. They found a
      statistical significant difference for the median number of days to clinical
      success (defined as patients' report of symptoms to be cured or much improved)
      favoring intranasal corticosteroids (6 days) over placebo (9 days), while the
      difference in proportion of patients reporting clinical success after 21 days of
      treatment was 20% favoring intranasal corticosteroids over placebo. CONCLUSION
      AND RECOMMENDATION: The evidence for the benefit of intranasal corticosteroids on
      symptom relief in adult patients with recurrent acute rhinosinusitis is rather
      limited (ie, 3 trials are available; the best evidence is derived from 1 low risk
      of bias trial providing moderate directness of evidence that intranasal
      corticosteroids may speed up relief of symptoms in patients with recurrent acute
      rhinosinusitis). A large methodologically rigorous randomized trial in antibiotic
      naive patients is needed to provide a more definite recommendation.

PMID- 24013139
TI  - Surgeon experience and complications with Transoral Robotic Surgery (TORS).
AB  - OBJECTIVE: To investigate surgeon preferences for perioperative management of
      transoral robotic surgery (TORS) and explore the frequency of postoperative
      complications. STUDY DESIGN: Retrospective survey. SETTING: Multi-institutional.
      SUBJECTS AND METHODS: An electronic survey was sent to over 300 TORS-trained
      surgeons in the United States identified by Intuitive Surgical, Inc.
      Participation was voluntary and solicited by email invitations to participate 3
      times over a 1-month period. RESULTS: A total of 2015 procedures were reported by
      45 respondent TORS-trained surgeons: 67% academic, 33% nonacademic. A minority of
      TORS procedures (n = 214, 10.6%) were performed on previously irradiated
      patients. Neck dissections were performed concurrently (58%) or staged (42%).
      Fewer than 6% of TORS procedures required tracheotomy or reconstruction. Most
      surgeons (62%) initiated oral intake on postoperative day 0-1. Of the patients
      who required readmission, bleeding (n = 62, 3.1%) was the most common cause
      followed by dehydration (n = 26, 1.3%). Other complications of surgery included
      tooth injury (n = 29, 1.4%), percutaneous endoscopic gastrostomy (PEG) dependency
      >6 months (n = 21, 1.0%), temporary hypoglossal nerve injury (n = 18, 0.9%), and
      lingual nerve injury (n = 11, 0.6%). A total of 6 deaths (0.3%) were reported
      within 30 days of TORS. All reported deaths were due to postoperative hemorrhage.
      The complication rate decreased significantly with higher surgeon case volume
      (>50 cases). CONCLUSIONS: TORS is associated with a low major complication rate,
      early initiation of oral intake, and a low rate of long-term PEG dependency.
      Postoperative hemorrhage was the most common cause of hospital readmission and
      postoperative mortality.

PMID- 24013140
TI  - Clinical assessment and treatment of the dysfunctional larynx after radiation.
AB  - OBJECTIVE: To review the pathophysiology of early and late radiation-related
      tissue changes, methods to differentiate these changes from disease recurrence,
      and treatment of these changes in the irradiated larynx. DATA SOURCES: Peer
      reviewed publications. REVIEW METHODS: PubMed database search.
      CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Early and late radiation-related changes
      in the larynx manifest variably between individual patients. Severe radiation
      related tissue changes in the larynx and recurrent malignancy share many clinical
      characteristics, and the presence of malignancy must be considered in these
      patients. Positron emission tomography may help select patients who need
      operative biopsy to rule out recurrence. In patients with a cancer-free but
      dysfunctional larynx, both surgical and nonsurgical treatment options, including
      hyperbaric oxygen, are available for attempted salvage. Further investigation is
      needed before hyperbaric oxygen can be considered standard-of-care treatment for
      these patients.

PMID- 24013141
TI  - Data resource profile: 1991 Canadian Census Cohort.
AB  - The 1991 Canadian Census Cohort is the largest population-based cohort in Canada
      (N=2,734,835). Prior to the creation of this Cohort, no national population-based
      Canadian cohort was available to examine mortality by socioeconomic indicators.
      The 1991 Canadian Census Cohort was created via the linkage of a sub-sample of
      respondents from the mandatory 1991 Canadian Census long-form to historical tax
      summary files, Canadian Mortality Database, Canadian Cancer Database, 1991 Health
      and Activity Limitation Survey and a sub-sample of the Longitudinal Worker File.
      Overall ascertainment of mortality and cancer is anticipated to be nearly
      complete and the Cohort is broadly representative of most groups in the Canadian
      population. The Cohort has been used to examine mortality outcomes by different
      indicators of socioeconomic status, occupational categories, ethnic groups,
      educational attainment, and for exposure to ambient air pollution. Results have
      shown that the estimated remaining years of life at age 25 differed substantially
      by income adequacy quintile, educational attainment, housing type and Aboriginal
      ancestry.

PMID- 24013143
TI  - [Role of heat flow generated by an abdominal cavity in monitoring of acute
      surgical pathology of abdominal organs].
AB  - Despite of significant development of modern surgery results of treatment of
      acute diffused peritonitis and acute intestinal obstruction are still
      unsatisfactory. Successful treatment of these conditions depends considerably on
      timely and adequate diagnosing as it gives a choice of optimal treatment tactics.
      Measuring of a human body heat flow in areas of organs affected by pathology in
      cases of acute diffused peritonitis and acute intestinal obstruction provides a
      possibility to improve the principles of early differential diagnosing, to form
      new approaches to treatment tactics and monitoring of general health status of a
      patient during early postoperative treatment. 47 patient suffering from acute
      diffused peritonitis and 42 patients suffering from acute intestinal obstruction
      have been examined; the patients were divided into groups based on abdominal
      cavity exudates character, intestinal obstruction type and intra-abdominal
      hypertension grade. Measurement of abdominal cavity heat flow was performed by a
      contact method with use of thermoelectric medical thermometer. Intra-abdominal
      hypertension was measured by generally used transvesical method. It has been
      established that abdominal cavity heat flow correlates with character of
      abdominal cavity exudates; this is also confirmed by reliable difference between
      serous peritonitis and fibrinopurulent peritonitis indices. Indices in case of
      acute intestinal obstruction are lower than ones in case of acute diffused
      peritonitis as there are no inflammatory changes of peritoneum. Development of
      intra-abdominal hypertension of grades 3-4 directly influences the heat flow
      extent; this is explained by accelerated and aggravated pathological changes of
      inner organs cased by the main disease. Thus, abdominal cavity heat flow fully
      reflects degree of purulent and inflammatory processes of abdominal cavity organs
      and can be used for additional diagnosing and clinical course monitoring. 

PMID- 24013142
TI  - Classifying chemical mode of action using gene networks and machine learning: a
      case study with the herbicide linuron.
AB  - The herbicide linuron (LIN) is an endocrine disruptor with an anti-androgenic
      mode of action. The objectives of this study were to (1) improve knowledge of
      androgen and anti-androgen signaling in the teleostean ovary and to (2) assess
      the ability of gene networks and machine learning to classify LIN as an anti
      androgen using transcriptomic data. Ovarian explants from vitellogenic fathead
      minnows (FHMs) were exposed to three concentrations of either 5alpha
      dihydrotestosterone (DHT), flutamide (FLUT), or LIN for 12h. Ovaries exposed to
      DHT showed a significant increase in 17beta-estradiol (E2) production while FLUT
      and LIN had no effect on E2. To improve understanding of androgen receptor
      signaling in the ovary, a reciprocal gene expression network was constructed for
      DHT and FLUT using pathway analysis and these data suggested that steroid
      metabolism, translation, and DNA replication are processes regulated through AR
      signaling in the ovary. Sub-network enrichment analysis revealed that FLUT and
      LIN shared more regulated gene networks in common compared to DHT. Using
      transcriptomic datasets from different fish species, machine learning algorithms
      classified LIN successfully with other anti-androgens. This study advances
      knowledge regarding molecular signaling cascades in the ovary that are responsive
      to androgens and anti-androgens and provides proof of concept that gene network
      analysis and machine learning can classify priority chemicals using experimental
      transcriptomic data collected from different fish species. 

PMID- 24013144
TI  - [Fibronectin and insulin-like growth factor-1 in pathogenesis of open-angle and
      pseudoexfoliative glaucoma].
AB  - The aim of the present investigation was to study the role of fibronectin and
      insulin-like growth factor-1 (IGF-1) in pathogenesis of primary open-angle and
      pseudoexfoliative glaucoma. Immune enzyme analysis was performed on aqueous
      humour of 480 patients with complicated cataracts on the background of primary
      open-angle and pseudoexfoliative glaucoma. The aqueous humour of patients with
      senile cataracts was used as control. The content of fibronectin and IGF-1 in
      aqueous humour was determined using appropriate kits (DRG-International Inc.,
      USA) in the absorbance wavelength range 420-450 nm. The obtained results were
      analyzed using Student's criteria and application of SPSS-13/80. Relatively high
      levels of fibronectin and IGF-1 were recorded in aqueous humour of patients with
      complicated cataracts (cataracts on the background of open-angle and
      pseudoexfoliative glaucoma), as compared to indices of both cytokines in the
      aqueous humour of control group patients. In mechanisms of eye drainage function
      impairment and intraocular pressure increase an important role belongs to in situ
      (i.e. in the eye membranes) produced fibronectin and IGF-1. 

PMID- 24013145
TI  - [Treatment of fractures of a mandible by means of onteeth compression-distraction
      apparatus].
AB  - The present work describes the elaboration of onteeth compression-distraction
      apparatus and the treatment method for mandible fractures within dentition using
      onteeth compression-distraction apparatus. The conclusions are made regarding
      advantage of onteeth compression-distraction apparatus over intermaxillary and
      wire fixation of the bone fragments, as well as over helical onteeth compression
      distraction apparatus.

PMID- 24013146
TI  - [Neutrophils expression of adhesion molecules in diabetic nephropaty patients].
AB  - CD11b and CD54 expression on neutrophils in patients with diabetic nephropathy
      (DN), arterial hypertension patients and healthy donors were examined.
      Development of DN associates with an increase of the number of CD11b and CD54
      positive cells and violation of cellular co-operation. In the conditions of
      diabetic microenvironment expression of adhesion molecules rises substantially,
      what may characterized the mechanism of connection between hyperglycemia and
      vascular and tissues injury at DN. Authentication of morphological and
      biochemical markers of intercellular co-operation must in a prospect assist the
      deeper understanding of pathogenic mechanisms of DN. 

PMID- 24013147
TI  - [Clinical electroencephalographic aspects of outcome prognosis of acute period of
      ischemic supratentorial stroke].
AB  - Clinical computed electroencephalographic examination of 120 patients in acute
      period of ischemic supratentorial stroke was made with the aim of outcome
      prognosis optimization. Prognostic value of stroke subtype evaluation using the
      Oxfordshire Community Stroke Project classification and the degree of initial
      neurological deficit (by NIHSS) in acute period of the stroke was clarified.
      Statistical significant correlations between parameters of
      electroencephalographic pattern in the onset of ischemic supratentorial stroke
      and stroke acute period outcome were established. Using logistic regression it
      was proved that combined specification of clinical stroke subtype by Oxfordshire
      Community Stroke Project classification and DAR coefficient of affected
      hemisphere in the onset of disease improves prediction of stroke acute period
      outcome. 

PMID- 24013148
TI  - [The role of endothelial dysfunction in progression of liver fibrosis and
      manifestation of sryoglobulinemia syndrome in patients with chronic hepatitis C].
AB  - The study of 78 patients with chronic hepatitis C is presented. It was found that
      emergence and progression of endothelium-dependent dysfunction of endothelium is
      combined with progression of liver fibrosis. The manifestation of clinical signs
      of the HCV-associated crioglobulinemia syndrome is registered in patients with
      stage F 3-4 liver fibrosis against the background of high concentration of the
      mixed cryoglobulins, rheumatoid factor of Ig M and the expressed endothelium
      dependent dysfunction of endothelium. 

PMID- 24013149
TI  - Trends in the prevalence of childhood asthma and allergy in Western part of
      Georgia.
AB  - Internatinal time trend analyses, using the ISAAC (Phase Three) protocol, have
      yielded variable results and observed a rise in prevalence especially in areas
      where allergic diseases were previously less common. In 2003 and 2012, we
      performed cross-sectional studies in Kutaisi (western part of Georgia)
      schoolchildren aged 6-7 and 13-14 yr., using the validated ISAAC methodology,
      aiming to provide the prevalence trends of asthma and allergy in this population.
      Both cross-sectional studies were carried out in the same city, same season and
      used identical methodologies. In 2003, number of participants in 6-7 and 13-14
      yrs old groups was 2666 and 2650 and in 2012 - 3039 and 2339 correspondently.
      Significant alteration in prevalence of asthma related symptoms was obtained in
      both age groups. The symptom of severe asthma had increased only in 13-14 year
      old adolescents and was not change in 6-7 year old group. There were significant
      increases (all to p < 0.001) in the symptoms of current sneezing (16.4% vs 8.7%
      and 28.4% vs 15.3% in 6-7 yr group and 13-14 yr group correspondently) and
      rhinoconjunctivitis (5.2% vs 2.9% and 9.6% vs 4.5% yr group and 13-14 yr group
      correspondently). Symptoms of current eczema (affecting flexural dermatitis) were
      increased in both age groups. The prevalence of asthma and allergies markedly
      increase among both age groups of schoolchildren in the western part of Georgia.
      The exact reasons for such trends remain to be explored. 

PMID- 24013150
TI  - [Peculiarities of health condition of Tbilisi metro workers accordind to age and
      length of service].
AB  - The purpose of the study was to evaluate the influence of professional factors on
      health condition of Tbilisi metro workers. Working conditions were analyzed;
      paraclinic study was conducted; health status according to age and length of
      service was investigated. It was found that age and length of service affects the
      health condition of the worker; cardiovascular and nervous system diseases are
      the most frequent. 

PMID- 24013151
TI  - [Changes of blood cell's morphological characteristics and their clinical
      significance].
AB  - The purpose of this article is the interpretation of the clinical value of blood
      cells' (erythrocytes, leukocytes, thrombocytes) morphological characteristics
      changes taking into the consideration results of our own long-term (1982-2012)
      investigations as well as literature data. Patients with hematological and
      nonhematological diseases as well as large groups of Georgia population (about
      30.000 persons, in age 2-81) were observed. By Gimsa-Romanovsky method stained
      blood smears were studied in light microscope. Changes of blood cells'
      morphological characteristics, observed by us and known in the literature, as
      well as ones revealed at first in this work, are presented according to the three
      branches of hemopoiesis. Possible changes of blood cells' morphological
      characteristics are described in details. Concrete changes in concrete diseases
      are presented in eight tables. Discussing the results the fact of the revealing
      of blood cells' morphological changes in some diseases, different by etiology,
      pathogenesis, clinical symptomatology and treatment, is accentuated. Some
      examples of the differentiation of different diseases by means of that nuances,
      which are revealed in microscope and which are not noticeable for the modern
      techniques, are presented. The significance of some specific changes of blood
      cells' morphological characteristics for the doubtless diagnostic of some
      concrete anomalies is shown. The list of changes which are revealed in this work
      but are not founded in the literature is presented. The conclusion is drawn that
      the nuances of blood cells' morphological changes revealed in light microscope
      allow to narrow the spectrum of additional investigations for the establishment
      of diagnosis. 

PMID- 24013152
TI  - [A comparative study of antiarrhythmic and antihypoxic effects of magnesium
      sulfate, its prolonged form and blockers of calcium channels].
AB  - The aim of the study is the comparative study of treatment of heart and brain
      damages during the hypoxia with magnesium sulfate, verapamil, diltiazem. As a
      result of the experiment carried out on rats it was proved that magnesium sulfate
      and its prolonged form are not less active than the blockers of calcium channels,
      such as verapamil and diltiazem. It is possible to avoid lethal fibrillations
      caused by calcium chloride with the help of 25% magnesium sulfate solution (after
      intraperitoneal administration with the dose of 1000 mg/kg) in case we make
      arrythmogenic injection 5 minutes after inputting magnesium sulfate solution.
      During the arrhythmia induced by calcium chloride prolonged form of magnesium
      sulfate is also effective only if we inject the drug subcutaneous 30 minutes
      before the arrythmogenic injection. If the interval is 5 minutes lethal
      fibrillations cant be avoided as the release of magnesium ions from the drug form
      is slowed down. The drugs containing magnesium ions also displayed cytoprotective
      activity on the model of normobaric hypoxia. This was resulted in the increase of
      protective index. Neuroprotective action of magnesium ions (in the condition of
      hypoxia) is caused by maintaining homeostasis of calcium ions and by inhibition
      of exocytosis of neuromediators in the synaptic cleft. Thus, magnesium sulfate
      and its prolonged form can be used with the purpose of pharmacocorrection of
      heart and brain injuries during hypoxic conditions. 

PMID- 24013153
TI  - [Study of acetylsalicylic acid role in the potentiation of antiamnesic and
      neuroprotective properties of piracetam in rats with alloxan diabetes].
AB  - It has been established that prolonged alloxan-induced hyperglycemia in rats
      potentiates amnesic properties of scopolamine hydrobromide. It was characterized
      by shortening of the latent period by 44% (p<0,01) and by 47,7% (p<0,05) after 24
      hours and on the 20th day of conditioned passive avoidance test. This effect was
      accompanied by increase in oxidative modification of proteins and nitric oxide
      synthesis in the cerebral cortex. Along with this, a significant enhancement of
      ADP- and collagen-induced platelet aggregation was observed. These processes may
      play the leading role in the development of cognitive deficit in diabetes.
      Meanwhile, co-administration of piracetam with acetylsalicylic acid was
      accompanied by an expressed antiamnetic potential - the reduction of early
      markers of proteins degradation (aldehydephenylhydrazones, APH) by 21,7% (p<0,05)
      and late markers of proteins degradation (ketonephenylhydrazones, KPH) by 23,8%
      (p<0,001) was noted. This combination was 15,7% (p<0,05) more active than
      piracetam according to the effect upon KPH. NO2-/NO3- level was also decreased by
      30,3% (p<0,05) in comparison with alloxan-diabetic rats. The significant anti
      platelet effect was observed: degree of collagen-induced platelet aggregation was
      reduced by 56,8% (p<0,01), ADP (5 MUmol/l)-induced - by 31,7% (p<0,01), ADP (20
      MUmol/l)-induced - by 47,3% (p<0,01) as compared to the hyperglycemic rats. Such
      an increase in nootropic activity of piracetam may be assumed to be directly
      related to the ability of acetylsalicylic acid to improve microcirculation in the
      ischemic areas of the brain in diabetes and probably to its neuroprotective
      potential. 

PMID- 24013154
TI  - Pancreatic cell proteome - qualitative characterization and function.
AB  - The macromolecular protein complex form adult white rat pancreas has been
      obtained and partially characterized. The most important distinguishing
      characteristics of the complex is the thermostability of its components. Using
      polyacrylamid gel by electrophoresis and chromatography of hydrophobic
      interaction has been established, that the components with relatively high (45-60
      kD) molecular weight, are hydrophobic, while the low molecular weight components
      (11-12 kD) corresponds to hydrophilic proteins according to its column retention
      time. Participation of TPC in the regulation of the homotypic cell growth was
      determined. It is shown that the pancreatic TPC through inhibition of
      transcription decreases cell mitotic activity in growing rats. It is also shown
      that this complex is involved in pancreas regeneration processes. On the basis of
      the qualitative characteristics and cell growth regulatory function of this
      macromolecular protein complex described by us, it can be considered as a
      pancreatic cell proteome. 

PMID- 24013155
TI  - [Stress, anxiety, depression and erectile dysfunction in patients with diabetes
      mellitus].
AB  - It was studied the erectile dysfunction (ED), the severity of depression and
      stress in patients with diabetes mellitus (DM) in the stage of compensation and
      decompensation, also investigated the relationship between the duration of the
      disease and the clinical manifestation of the various forms of ED. On a material
      of 293 male patients aged 17-60 years. The duration of diabetes ranged from 6
      months to 30 years (at avarage - 17,4+/-17,5 years). Performed routine and
      special methods of investigation (pharmacodopplerography), also fixed
      psychogenic, organic and mixed forms of erectile dysfunction in correlation with
      the clinical form of the current CD according International index of Erectile
      function (EF) and the tables of Juneman et al. Found that in patients with type I
      and II diabetes anxiety and depression were found in 32.1 % of cases, and were
      accompanied by ED. In the state of decompensation of diabetes mellitus
      manifestation of anxiety, depression and erectile dysfunction were observed more
      often than in a state of long-term compensation. Between the increase in the
      period of limitation of the DM and the incidence of organic and mixed forms of ED
      there is a direct correlation, and between the increase of diabetes duration and
      the frequency of occurrence of psychogenic form of erectile dysfunction -
      inversly relationship. 

PMID- 24013156
TI  - Learning difficulties: a retrospective study of their co morbidity and continuity
      as indicators of adult criminal behaviour in 18-70-year-old prisoners.
AB  - The development of learning difficulties is associated with problems in external
      (executive) and extensive behaviour in a co-occurrence with psycho-emotional
      problems beginning from pre-school, school age, and adolescence up to adulthood.
      Through the current survey, we aim to emphasise the early role of learning
      difficulties during the school age and adolescence of prisoners and their effects
      on the onset of offending behaviours in adulthood, such as criminal behaviour.
      Altogether, we studied 117 Greek adult prisoners from 18 to 70 years old who were
      accused of different types or degrees of offences. Through statistical analyses,
      the following factors were observed with high statistical significance as early
      indicators of criminal behaviour in the adult lives of the prisoners: (i)
      learning difficulties, (ii) family problems, (iii) behaviour disorders, (iv)
      developmental disorders, and (v) psycho-emotional disorders. As a result, the
      learning difficulties were assumed to be the most decisive factor in the
      developmental progression of prisoners because they manifested early in the
      prisoners' lives, weakened the prisoners to be competitive and robust, provoked a
      bad self-image and low self-esteem, and, in the frame of a weak or negative
      family and educational environment, they accompanied antisocial behaviour and
      psycho-emotional disorders even from adolescence, which continued into adulthood.

PMID- 24013157
TI  - Understanding physical activity and motivations for children with developmental
      coordination disorder: an investigation using the theory of planned behavior.
AB  - Developmental coordination disorder (DCD) is a neurodevelopmental condition,
      affecting approximately 5-6% of children. Previous research has consistently
      found children with DCD being less physically active compared to typically
      developing (TD) children; however, the psychosocial factors associated with
      physical activity for children with DCD are poorly understood. The purpose of
      this study was to examine how theory-based physical activity cognitions impacts
      physical activity behaviors for children with and without DCD. Participants
      included a sample of boys (N=61, Mage=13.25 +/-.46) with DCD (n=19) and without
      DCD (n=42), drawn from a larger prospective cohort study. A questionnaire with
      psychosocial measures was first administered, and accelerometers were used to
      assess their physical activity behavior over the subsequent week. Findings
      indicate that DCD was significantly associated with lower physical activity
      (F(1,58)=6.51, p<.05), and poorer physical activity cognitions (F(4,56) Wilks
      Lambda=2.78, p<.05). Meditational analyses found attitudes (B=.23, p<.05) and
      subjective norms (B=.31, p<.05) partially mediating the relationship between DCD
      and physical activity. Overall, this study further confirms that the activity
      deficit that exists among boys with DCD, and that the relationship is partially
      mediated through some physical activity cognitions. Interventions should target
      the perceived approval of influential people, and the personal evaluations of
      physical activity for boys with motoric difficulties. These findings further
      emphasizes the discrepancy in physical activity that exist between boys with DCD
      and TD boys, and highlight the need to better understand the psychological
      factors related to physical activity for children with DCD.

PMID- 24013158
TI  - Impact of oxygen concentration on adult murine pre-antral follicle development in
      vitro and the corresponding metabolic profile.
AB  - Oxygen concentration during in vitro culture has a significant effect on the
      physiology of embryos, altering metabolic profile and developmental outcome.
      Although atmospheric oxygen has been used routinely for the culture of ovarian
      follicles, oxygen concentration may also be critical for follicle growth but the
      optimal concentration has not been determined. In this study, mechanically
      isolated primary and secondary follicles (80-140 um diameter) from adult mouse
      ovaries were cultured in serum-free conditions for 8 days in either 5 or 20%
      oxygen to determine growth (follicular diameter), morphology and viability. For
      each oxygen concentration, half of the medium was replaced on Days 2, 4 and 6 or
      on Day 4 only. In the latter group, metabolic analysis of spent follicular
      culture media was performed by (1)H-NMR. The proportion of viable, growing
      follicles was significantly (P < 0.0001) higher in 5% than in 20% oxygen (59%
      versus 8%). Reducing the frequency of medium replacement during culture in 5%
      oxygen resulted in significantly (P < 0.001) more viable follicles (79 versus
      46%). In 20% oxygen, poor follicular viability was observed irrespective of the
      frequency of medium replacement (8 and 10% respectively). Metabolic profiles
      showed marked differences in amino acid and carbohydrate utilization with respect
      to both oxygen concentration and between Days 4 and 8 of development. Metabolites
      which significantly discriminated between oxygen concentration at both time
      points were glucose consumption, lactate utilization, alanine, alanyl-glutamine,
      leucine and proline. In conclusion, the poor in vitro follicular development
      previously observed in minimal culture conditions may reflect the use of 20%
      oxygen. Frequent medium replenishment is not necessary and does not overcome the
      detrimental effect of high oxygen on follicle viability. Further optimization of
      culture conditions would benefit from metabolic analyses and the use of 5% oxygen
      should be tested further for impact on functional aspects of follicle culture
      such as steroid production which is currently unknown. 

PMID- 24013159
TI  - A second generation MRI contrast agent for imaging zinc ions in vivo.
AB  - A Zn2+ specific GdDOTA derivative containing two bis-(3-pyrazolyl) units was
      prepared and characterized. Unlike a previously reported Zn2+ binding agent, the
      new agent binds to human albumin both in the presence and absence of Zn2+.

PMID- 24013160
TI  - A Robust and Efficient Doubly Regularized Metric Learning Approach.
AB  - A proper distance metric is fundamental in many computer vision and pattern
      recognition applications such as classification, image retrieval, face
      recognition and so on. However, it is usually not clear what metric is
      appropriate for specific applications, therefore it becomes more reliable to
      learn a task oriented metric. Over the years, many metric learning approaches
      have been reported in literature. A typical one is to learn a Mahalanobis
      distance which is parameterized by a positive semidefinite (PSD) matrix M. An
      efficient method of estimating M is to treat M as a linear combination of rank
      one matrices that can be learned using a boosting type approach. However, such
      approaches have two main drawbacks. First, the weight change across the training
      samples maybe non-smooth. Second, the learned rank-one matrices might be
      redundant. In this paper, we propose a doubly regularized metric learning
      algorithm, termed by DRMetric, which imposes two regularizations on the
      conventional metric learning method. First, a regularization is applied on the
      weight of the training examples, which prevents unstable change of the weights
      and also prevents outlier examples from being weighed too much. Besides, a
      regularization is applied on the rank-one matrices to make them independent. This
      greatly reduces the redundancy of the rank-one matrices. We present experiments
      depicting the performance of the proposed method on a variety of datasets for
      various applications.

PMID- 24013161
TI  - Characterization and performance assessment of solid dispersions prepared by hot
      melt extrusion and spray drying process.
AB  - The present study investigated effect of manufacturing methods such as hot melt
      extrusion (HME) and spray drying (SD) on physicochemical properties,
      manufacturability, physical stability and product performance of solid
      dispersion. Solid dispersions of compound X and PVP VA64 (1:2) when prepared by
      SD and HME process were amorphous by polarized light microscopy, powder X-ray
      diffractometry, and modulated differential scanning calorimetry analyses with a
      single glass transition temperature. Fourier transform infrared (FT-IR) and Raman
      spectroscopic analyses revealed similar molecular level interactions between
      compound X and PVP VA64 as evident by overlapping FT-IR and FT Raman spectra in
      SD and HME solid dispersions. The compactibility, tabletability, disintegration
      and dissolution performance were similar for solid dispersions prepared by both
      processing techniques. Differences in material properties such as surface area,
      morphological structure, powder densities, and flow characteristics were observed
      between SD and HME solid dispersion. The SD solid dispersion was physically less
      stable compared to HME solid dispersion under accelerated stability conditions.
      Findings from this study suggest that similar product performance could be
      obtained if the molecular properties of the solid dispersion processed by two
      different techniques are similar. However differences in material properties
      might affect the physical stability of the solid dispersions. 

PMID- 24013162
TI  - Silver(I) complexes of tris(pyrazolyl)borate ligands bearing six trifluoromethyl
      and three additional electron-withdrawing substituents.
AB  - Sodium salts of two new tris(pyrazolyl)borates [HB(4-Cl-3,5-(CF3)2Pz)3](-) and
      [HB(4-(NO2)-3,5-(CF3)2Pz)3](-), which are not only highly fluorinated, but also
      loaded with additional electron-withdrawing substituents, have been synthesized
      by reacting 4-Cl-3,5-(CF3)2PzH or 4-(NO2)-3,5-(CF3)2PzH with NaBH4 under nitrogen
      in a solventless process, and isolated after a work up in tetrahydrofuran (THF)
      or diethyl ether (Et2O), as their THF or Et2O adducts. Metathesis of these sodium
      salts with AgOTf in THF leads to [HB(4-Cl-3,5-(CF3)2Pz)3]Ag(THF) and [HB(4-(NO2)
      3,5-(CF3)2Pz)3]Ag(THF). The corresponding cis-cyclooctene (c-COE) complexes [HB(4
      Cl-3,5-(CF3)2Pz)3]Ag(c-COE) and [HB(4-(NO2)-3,5-(CF3)2Pz)3]Ag(c-COE) were
      obtained by displacing THF with cis-cyclooctene. The related [HB(3,5
      (CF3)2Pz)3]Ag(c-COE) can also be obtained via a similar process. X-ray crystal
      structures show that [HB(4-(R)-3,5-(CF3)2Pz)3]Ag(c-COE) (R = H, Cl, NO2) feature
      pseudo-tetrahedral silver sites supported by kappa(3)-bound tris(pyrazolyl)borate
      ligands. [HB(4-(NO2)-3,5-(CF3)2Pz)3]Ag(c-COE) displays the smallest upfield shift
      of the alkene carbon peak (versus free alkene) followed by [HB(4-Cl-3,5
      (CF3)2Pz)3]Ag(c-COE) and [HB(3,5-(CF3)2Pz)3]Ag(c-COE). Experimental and
      computational data indicate very electron poor silver(I) sites in all three [HB(4
      (R)-3,5-(CF3)2Pz)3]Ag(c-COE) adducts with minimal Ag -> (cis-cyclooctene)
      backbonding. Although the impact of R (H, Cl, NO2) on the alkene carbon chemical
      shift of these adducts and the olefin pi/pi* populations is small, the (13)C NMR
      chemical shifts and NBO analysis suggest that [HB(4-(NO2)-3,5-(CF3)2Pz)3]Ag(c
      COE) possesses the most electrophilic metal site, which correlates with the pKa
      values of the free pyrazoles. [HB(4-(R)-3,5-(CF3)2Pz)3]Ag(c-COE) adducts
      effectively catalyze the insertion of the carbene moiety of ethyl diazoacetate
      into C-H bonds of 2,3-dimethylbutane. The [HB(4-(NO2)-3,5-(CF3)2Pz)3]Ag(c-COE)
      catalyst shows a higher selectivity for primary C-H bonds compared to the
      reactions catalyzed by [HB(3,5-(CF3)2Pz)3]Ag(c-COE).

PMID- 24013163
TI  - Broad spectrum photoluminescent quaternary quantum dots for cell and animal
      imaging.
AB  - Highly luminescent oil-soluble quaternary Zn-Ag-In-Se (ZAISe) quantum dots (QDs)
      with extremely wide emission covering the spectral range from 550 to 1000 nm have
      been synthesized for the first time. These broadly emissive quaternary QDs are
      demonstrated to have greater potential in the use of one probe for multi-spatial
      scale biomedical imaging than binary CdTe and ternary Cu-In-S QDs. 

PMID- 24013164
TI  - Extraction and separation of proteins by ionic liquid aqueous two-phase system.
AB  - A satisfactory protocol of protein extraction and separation has been established
      based on the ionic liquid aqueous two-phase system (IL-ATPS) for the purification
      of bioactive substances. Compared with the effects of eight different ionic
      liquids, 1-octyl-3-methylimidazolium bromide ([omim][Br]) was selected as the
      suitable ionic liquid. Based on the single-factor experiment, an initial serial
      investigative test was used to identify the optimal conditions of the extraction.
      Owing to their different isoelectric points, bovine serum albumin (BSA),
      hemoglobin (Hb) and lysozyme (Lys) were used to determine the effect of pH value
      on the protein extraction. Trypsin (Try) was used to confirm the protein
      activity. The linearity for analyzing BSA, Hb, Try and Lys was in the
      concentration range of 0.05-1.00 mg ml(-1), 0.025-1 mg ml(-1), 0.01-1.00 mg ml(
      1) and 0.01-1.00 mg ml(-1), respectively, with a correlation coefficient of
      between 0.9985 and 0.9999. Limits of detection (LODs) were 16.47-7.02 MUg ml(-1)
      and RSDs of inter-day stability were less than 2.9%. Repeatability and precision
      were respectively lower than 5.3% and 1.1%. Under the optimum conditions, the
      average recoveries of BSA, Hb, Try and Lys were 90.5%, 94.5%, 92.7% and 93.8% and
      the obtained RSDs were 1.19%, 1.23%, 1.34% and 1.04%, respectively. According to
      UV spectra, conductivity, dynamic light scattering (DLS), and transmission
      electron microscope (TEM) images, the cluster phenomenon originating from IL
      itself or combined with protein was evaluated. As the driving forces which are
      involved in the partitioning of protein between the IL-rich phase and the
      phosphate phase, the cluster phenomenon could, in principle, be applied to a
      variety of different samples and exhibited potential value. 

PMID- 24013165
TI  - State efforts to promote continuity of coverage and care under the Affordable
      Care Act.
AB  - Many states have worked tirelessly over the past two years to develop health
      insurance exchanges and prepare for the expansion of their Medicaid programs in
      order to meet the requirements of the Patient Protection and Affordable Care Act.
      Programs to expand coverage, however, do not necessarily ensure seamlessness for
      many individuals who are likely to experience shifts in program eligibility due
      to changing circumstances (e.g., income fluctuations, family composition changes,
      etc.). A number of states are actively working to limit the impact of changes in
      program eligibility by developing policies that limit either the incidence of
      program eligibility changes and/or the impact those changes have on individual
      consumers. Various emerging state approaches take into account program history,
      the desire for state flexibility, and the political and operational challenges
      states face in developing coverage expansions that work for consumers,
      stakeholders, and policy makers. 

PMID- 24013166
TI  - Is it rationing if the public decides?

PMID- 24013167
TI  - Posttransplant lymphoproliferative disorder of the central nervous system.
AB  - Posttransplant lymphoproliferative disorder (PTLD) involves uncommon, severe
      complications following the transplantation of solid organs, bone marrow and stem
      cells. Despite comprising mainly lymphoid proliferations that are predominantly
      driven by lymphotropic Epstein-Barr virus (EBV) infections, PTLD often displays
      substantial morphologic heterogeneity that can pose diagnostic challenges. With
      the steady increase in transplantations accompanied by potent immunosuppressive
      therapy, it is important to heighten awareness of this entity among clinicians
      and pathologists. In comparison to systemic PTLD, cases that primarily manifest
      in the central nervous system (CNS) are reported to be more severe and to exhibit
      unique characteristics. So far, only isolated cases and small series have been
      reported describing CNS involvement in PTLD. In this article, we review the
      current knowledge, focusing on the histopathological features of primary CNS
      lymphoproliferative disorders following organ transplantation. 

PMID- 24013168
TI  - The experience of sudden cardiac arrest: becoming reawakened to life.
AB  - BACKGROUND: Sudden cardiac arrest (SCA) is an event that has tremendous impact on
      the physical, cognitive and emotional well-being of individuals. Clinical
      experience and results of various studies indicate that survivors, in addition to
      having problems related to the underlying disease, have unique needs as a result
      of the cardiac arrest. AIM: The main purpose of this study was to describe
      survivors' experiences following SCA and resuscitation in order to gain knowledge
      of the effect of this experience on the needs and concerns of the survivors.
      METHODS: This qualitative study draws on interpretive phenomenology. The sample
      was purposive and data were generated through two semi-structured interviews.
      RESULTS: Seven men aged 50 to 54 years participated. Participants' experience is
      reflected in the following themes: feelings of insecurity and the need for
      support; striving to regain former life; emotional challenges; responding to
      symptoms; and a new view on life. CONCLUSION: The findings illustrate complex
      effects of the cardiac arrest on the survivor's life. Support after hospital
      discharge needs to be organized in a more structured fashion. The need for
      security and support was fundamental and should be addressed with continuity and
      vigilance in health care.

PMID- 24013169
TI  - Evaluating the role of Cardiac Genetics Nurses in inherited cardiac conditions
      services using a Maturity Matrix.
AB  - BACKGROUND: Cardiovascular disease is a leading cause of death worldwide and
      genetic risk factors play a role in nearly all such cases. In the UK, health
      service capacity to meet either current or future estimated needs of people
      affected by inherited cardiac conditions (ICCs) is inadequate. In 2008 the
      British Heart Foundation funded nine three-year Cardiac Genetics Nurse (CGN)
      posts across England and Wales to enhance ICC services. The CGNs were experienced
      cardiac nurses who had additional training in genetics and acted to coordinate
      cardiac and genetics service activities. AIM: To create and apply a framework
      against which progress in ICC service improvement could be measured over time
      following the CGN appointments. METHODS: A performance grid (Maturity Matrix, MM)
      articulating standards in five domains against stages of ICC service development
      was created by stakeholders through a consensus approach. The MM was used to
      guide staged self-assessments by the CGNs between 2009 and 2011. A six-point
      scale was used to locate progress from 'emerging' to 'established', represented
      graphically by spider diagrams. RESULTS: Progress in all domains was significant
      for new, emerging and established services. It was most notable for effective
      utilisation of care pathways and efficient running of clinics. Commitment to
      family-centred care was evident. CONCLUSION: The ICC-MM provided a comprehensive
      framework for assessing ICC services and has merit in providing guidance on
      development. CGNs can help integrate care across specialisms, facilitating the
      development of effective and sustainable ICC services at new, developing, and
      more established ICC service locations.

PMID- 24013170
TI  - Quality of life among patients with abdominal aortic aneurysm undergoing
      endografting in Taiwan.
AB  - BACKGROUND: The use of endovascular aneurysm repair (EVAR) as a treatment for
      abdominal aortic aneurysm (AAA) has started to become popular in Taiwan. Quality
      of life is considered an indicator of clinical outcome, and self-management and
      health literacy have been identified as significant contributors to quality of
      life. However, the research on these three variables, and relationships among
      them in AAA patients who have undergone EVAR, is limited. AIMS: The purpose of
      this study is to examine the relationship between self-management, health
      literacy and quality of life in AAA patients who have undergone EVAR in Taiwan.
      METHODS: This study uses a cross-sectional design with convenience sampling. A
      total of 105 patients were sampled in the outpatient clinic when they returned
      for a follow-up visit to a veterans' general hospital in Taiwan between May 2011
      and June 2012. Four questionnaires (demographic, self-management, health
      literacy, quality of life) were used to collect data. Regarding the relationship
      among these variables, Pearson correlations and hierarchical logistic regression
      were used to analyze the relationship. RESULTS: Self-management has a 73%
      mediation effect and an indirect effect of 13.51 on the relationship between
      health literacy and quality of life, while education and exercise habit has a 57%
      mediation effect and an indirect effect of 6.20 on this same relationship.
      CONCLUSION: These findings can be used to identify specific populations who have
      more risk for worse outcomes. They can then be provided with education to promote
      exercise behavior and to enhance self-management to achieve better quality of
      life.

PMID- 24013171
TI  - Magnetic domain patterns on strong perpendicular magnetization of Co/Ni
      multilayers as spintronics materials: II. Numerical simulations.
AB  - Magnetic domains in ultrathin films form domain patterns, which strongly depend
      on the magnetic anisotropy. The magnetic anisotropy in Co/Ni multilayers changes
      with the number of layers. We provide a model to simulate the experimentally
      observed domain patterns. The model assumes a layer-dependent magnetic
      anisotropy. With the anisotropy parameter estimated from experimental data, we
      reproduce the magnetic domain patterns. 

PMID- 24013172
TI  - Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and
      replication.
AB  - Faithful propagation of DNA methylation patterns during DNA replication is
      critical for maintaining cellular phenotypes of individual differentiated cells.
      Although it is well established that Uhrf1 (ubiquitin-like with PHD and ring
      finger domains 1; also known as Np95 and ICBP90) specifically binds to hemi
      methylated DNA through its SRA (SET and RING finger associated) domain and has an
      essential role in maintenance of DNA methylation by recruiting Dnmt1 to hemi
      methylated DNA sites, the mechanism by which Uhrf1 coordinates the maintenance of
      DNA methylation and DNA replication is largely unknown. Here we show that Uhrf1
      dependent histone H3 ubiquitylation has a prerequisite role in the maintenance
      DNA methylation. Using Xenopus egg extracts, we successfully reproduce
      maintenance DNA methylation in vitro. Dnmt1 depletion results in a marked
      accumulation of Uhrf1-dependent ubiquitylation of histone H3 at lysine 23. Dnmt1
      preferentially associates with ubiquitylated H3 in vitro though a region
      previously identified as a replication foci targeting sequence. The RING finger
      mutant of Uhrf1 fails to recruit Dnmt1 to DNA replication sites and maintain DNA
      methylation in mammalian cultured cells. Our findings represent the first
      evidence, to our knowledge, of the mechanistic link between DNA methylation and
      DNA replication through histone H3 ubiquitylation. 

PMID- 24013173
TI  - Two replication fork maintenance pathways fuse inverted repeats to rearrange
      chromosomes.
AB  - Replication fork maintenance pathways preserve chromosomes, but their faulty
      application at nonallelic repeats could generate rearrangements causing cancer,
      genomic disorders and speciation. Potential causal mechanisms are homologous
      recombination and error-free postreplication repair (EF-PRR). Homologous
      recombination repairs damage-induced DNA double-strand breaks (DSBs) and single
      ended DSBs within replication. To facilitate homologous recombination, the
      recombinase RAD51 and mediator BRCA2 form a filament on the 3' DNA strand at a
      break to enable annealing to the complementary sister chromatid while the RecQ
      helicase, BLM (Bloom syndrome mutated) suppresses crossing over to prevent
      recombination. Homologous recombination also stabilizes and restarts replication
      forks without a DSB. EF-PRR bypasses DNA incongruities that impede replication by
      ubiquitinating PCNA (proliferating cell nuclear antigen) using the RAD6-RAD18 and
      UBC13-MMS2-RAD5 ubiquitin ligase complexes. Some components are common to both
      homologous recombination and EF-PRR such as RAD51 and RAD18. Here we delineate
      two pathways that spontaneously fuse inverted repeats to generate unstable
      chromosomal rearrangements in wild-type mouse embryonic stem (ES) cells. Gamma
      radiation induced a BLM-regulated pathway that selectively fused identical, but
      not mismatched, repeats. By contrast, ultraviolet light induced a RAD18-dependent
      pathway that efficiently fused mismatched repeats. Furthermore, TREX2 (a 3'->5'
      exonuclease) suppressed identical repeat fusion but enhanced mismatched repeat
      fusion, clearly separating these pathways. TREX2 associated with UBC13 and
      enhanced PCNA ubiquitination in response to ultraviolet light, consistent with it
      being a novel member of EF-PRR. RAD18 and TREX2 also suppressed replication fork
      stalling in response to nucleotide depletion. Interestingly, replication fork
      stalling induced fusion for identical and mismatched repeats, implicating faulty
      replication as a causal mechanism for both pathways. 

PMID- 24013174
TI  - Cyclin A regulates kinetochore microtubules to promote faithful chromosome
      segregation.
AB  - The most conspicuous event in the cell cycle is the alignment of chromosomes in
      metaphase. Chromosome alignment fosters faithful segregation through the
      formation of bi-oriented attachments of kinetochores to spindle microtubules.
      Notably, numerous kinetochore-microtubule (k-MT) attachment errors are present in
      early mitosis (prometaphase), and the persistence of those errors is the leading
      cause of chromosome mis-segregation in aneuploid human tumour cells that
      continually mis-segregate whole chromosomes and display chromosomal instability.
      How robust error correction is achieved in prometaphase to ensure error-free
      mitosis remains unknown. Here we show that k-MT attachments in prometaphase cells
      are considerably less stable than in metaphase cells. The switch to more stable k
      MT attachments in metaphase requires the proteasome-dependent destruction of
      cyclin A in prometaphase. Persistent cyclin A expression prevents k-MT
      stabilization even in cells with aligned chromosomes. By contrast, k-MTs are
      prematurely stabilized in cyclin-A-deficient cells. Consequently, cells lacking
      cyclin A display higher rates of chromosome mis-segregation. Thus, the stability
      of k-MT attachments increases decisively in a coordinated fashion among all
      chromosomes as cells transit from prometaphase to metaphase. Cyclin A creates a
      cellular environment that promotes microtubule detachment from kinetochores in
      prometaphase to ensure efficient error correction and faithful chromosome
      segregation. 

PMID- 24013175
TI  - Evaluation of cardiac functions of patients with benign joint hypermobility
      syndrome.
AB  - We sought to investigate whether echocardiography with tissue Doppler imaging
      identifies myocardial dysfunction in children with benign joint hypermobility
      syndrome (BJHS). This cross-sectional study enrolled 75 children with BJHS and 70
      healthy children. We performed detailed echocardiography in individuals with BJHS
      without inherited connective tissue disorders. Any congenital or acquired cardiac
      disease was excluded by clinical and echocardiographic examination. Both groups
      were similar in terms of age, sex, and body mass index. The diameter of the
      aortic annulus and sinus valsalva were wider in patients with BJHS. There was no
      significant differences in ejection fraction or mitral and tricuspid annular
      plane systolic excursion between the two groups. Pulsed-wave Doppler-derived E/A
      ratios in mitral and tricuspid valves were similar in both groups. Deceleration
      time of early mitral inflow was prolonged in patients with BJHS. Mitral and
      tricuspid annulus Ea velocity were significantly lower in children with BJHS. Ea,
      Aa, and Ea/Aa ratios in the interventricular septum, left ventricle posterior
      wall, and right ventricle free wall were lower in patients with BJHS than in the
      control group. The E/Ea ratio was greater in patients with BJHS than in the
      control group. Isovolumic relaxation time and right-ventricular (RV) and left
      ventricular (LV) myocardial performance indices (MPIs) were greater in patients
      with BJHS. This study showed the diastolic dysfunction in patients with BJHS. In
      addition, we detected increased LV and RV MPI. We believe that BJHS may affect
      proteins of the myocardial cytoskeleton and extracellular matrix. 

PMID- 24013176
TI  - Morphology of interatrial defects created by interventional techniques in a
      neonatal animal model.
AB  - Pathological details are lacking of various techniques used for interatrial
      defect (IAD) creation in lesions requiring mixing or with left atrial
      hypertension. Therefore, the morphology of the IAD created by different
      interventional techniques is described. The atrial septa of ten euthanized
      piglets (seven at <3 days and three at 2 weeks of age) were surgically exposed.
      In pigs of both ages, a needle-created communication was dilated with
      angioplasty, cutting, and cryoplasty balloons. A stent was also implanted in a
      newborn pig. By way of a patent foramen ovale (PFO) in newborns, angioplasty and
      septostomy balloons and a stent created IADs. The morphology of the IAD was
      directly imaged and the size measured. Newborn piglets had noticeably thinner
      atrial septa, and a PFO was still present. Static balloon dilation created a
      circular IAD equivalent to the balloon diameter (3 and 6 mm) in both the created
      defects of pigs of both ages and the neonatal PFO. A 3-mm cutting balloon (CB)
      produced a 2-mm triangular IAD (corresponding to atherotomes) in pigs of both
      ages. Premounted stents, by way of a created defect or PFO, led to circular IADs
      equivalent to balloon diameter. The 3-mm cryoplasty balloon created a large 5 * 4
      mm IAD in the newborn pig; however, the IAD measured only 2 * 1-mm at 2 weeks. By
      way of a neonatal PFO, a septostomy balloon (inflated to 2 cc) created a 3-mm
      circular IAD. In neonatal piglet hearts, static balloon angioplasty, CBs, and
      stents created a predictable IAD. Cryoplasty balloons created highly variable
      defects.

PMID- 24013177
TI  - Current world literature. Cardiovascular system.

PMID- 24013179
TI  - Re: novel susceptibility variants at 10p12.31-12.2 for childhood acute
      lymphoblastic leukemia in ethnically diverse populations.

PMID- 24013180
TI  - The novel susceptibility variants for childhood acute lymphoblastic leukemia.

PMID- 24013182
TI  - External validation of the RENAL nephrometry score nomogram for predicting high
      grade renal cell carcinoma in solid, enhancing, and small renal masses.
AB  - PURPOSE: To confirm predictive accuracies of the RENAL nephrometry score (RNS)
      nomogram for identifying malignancy and high-grade renal cell carcinoma (RCC) in
      an external cohort of small renal masses (SRMs). METHODS: A total of 1,129
      patients who underwent extirpative renal surgery for solid and enhancing cT1
      renal tumors between 2005 and 2012 at a single institution were included in the
      validation cohort. A single uro-radiologist utilized computed tomography image
      reconstruction to classify tumors according to the RNS. The area under the curve
      (AUC) and calibration plots were used to determine predictive accuracies of
      malignancy and high-grade models of the RNS nomogram. RESULTS: Malignant and high
      grade tumors were identified in 1,012 (89.6%) and 389 (38.4%) patients with cT1
      tumors, and in 658 (87.3%) and 215 (32.6%) patients with cT1a tumors,
      respectively. Predictive performances of the nomogram for malignancy and high
      grade models revealed AUCs of 0.722 and 0.574 for cT1 tumors, and 0.727 and 0.495
      for cT1a tumors, respectively. The predictive value of the malignancy model was
      comparable to that of the model-development cohort (AUC = 0.76); however, the
      predictive value of the high-grade model was inferior to that of the model
      development cohort (AUC = 0.73). CONCLUSIONS: Unlike previous validation studies,
      we report inferior predictive performance of the RNS nomogram for discriminating
      high-grade RCC in solid and enhancing SRMs. This suggests that the RNS nomogram
      may be unreliable for preoperatively predicting high-grade RCC in SRMs, in which
      tumor size, the key determinant of high-grade RCC, is a limiting factor.

PMID- 24013181
TI  - Open versus laparoscopic partial nephrectomy for clinical T1a renal masses: a
      matched-pair comparison of 280 patients with TRIFECTA outcomes (RECORd Project).
AB  - AIM OF THE STUDY: To report a matched-pair comparative analysis between open
      (OPN) and laparoscopic partial nephrectomy (LPN) for clinical (c) T1a renal
      masses from a large prospective multicenter dataset. MATERIALS AND METHODS: The
      RECORd Project includes all patients who underwent OPN and LPN for kidney cancer
      between January 2009 and January 2011 at 19 Italian centers. Open and
      laparoscopic groups were compared regarding clinical, surgical, pathologic,
      functional results and TRIFECTA outcome. Multivariable logistic regression models
      were used to analyze predictors of WIT >25 min, surgical complications (SC) and
      the achievement of the TRIFECTA outcome. RESULTS: Overall, 301 patients had OPN
      and 149 LPN. Groups were matched 1:1 (140 matched pairs) for clinical diameter,
      tumor location and type of indication. Laparoscopic partial nephrectomy was
      associated with a significantly mean longer WIT (19.9 vs. 15.1 min; p < 0.001),
      and it was an independent predictor of a WIT >25 min (RR 6.29, p < 0.0001). The
      TRIFECTA was achieved in 78.6 and 74.3% after OPN and LPN (p = ns), respectively,
      and the surgical approach was not a predictor of a negative TRIFECTA and SC at
      multivariable analysis. At 6-month follow-up, no significant differences were
      observed between the OPN and LPN group both in estimated glomerular filtration
      rate (eGFR) (?GFR 1.1 vs. 4.1 mL/min) and in new-onset stage III-V chronic kidney
      disease (CKD) rate (0 vs. 0.7%). CONCLUSION: No significant difference in
      achieving the TRIFECTA outcome was reported after OPN and LPN. LPN was associated
      with a significantly longer WIT. However, eGFR at 6-month follow-up did not
      differ significantly between the two surgical approaches.

PMID- 24013183
TI  - Prevalence of antibodies to European porcine influenza viruses in humans living
      in high pig density areas of Germany.
AB  - The risk of zoonotic human infection caused by European porcine influenza virus
      strains was estimated in German regions with a high pig density. Sera from 622
      healthy volunteers were collected between April 2009 and November 2011, mainly in
      Westphalia and western Lower Saxony. These included 362 subjects with
      occupational contact to pigs and 260 blood donors without any direct exposition
      to pigs. Samples were analysed by the haemagglutination inhibition (HI) assay
      against a panel of six swine viruses of subtypes avian-like H1N1 and human-like
      H3N2 as well as against human H1N1 and H3N2 viruses including the pandemic H1N1
      strain of 2009. Reciprocal HI titres >=20 were quoted as seroreactive. Compared
      to the control group, a significantly higher proportion of subjects with direct
      contact to pigs exhibited seroreactivity against porcine antigens of the avian
      like H1N1 (37.0 %/7.7 %), the human-like H3N2 (59.7 %/43.1 %), the pandemic H1N1
      strain of 2009 (51.7 %/26.5 %) and against a historic seasonal H3N2 strain that
      is closely related antigenetically to currently circulating human-like H3N2
      viruses of European pigs (57.5 %/36.5 %). This trend was also observed when a
      reciprocal HI titre >=40 was chosen as cut-off. Particularly, in younger
      subjects, the differences in seroreactivity against porcine strains between the
      exposed and non-exposed group were significant. The data indicate a higher risk
      of infection in the exposed individuals.

PMID- 24013184
TI  - Anti-biofilm activity of low-molecular weight chitosan hydrogel against Candida
      species.
AB  - Candida invasive infections have increased in frequency during the last decades.
      Such infections are often associated to medical indwelling devices like central
      venous catheter. The recurrent nature and difficulties in the treatment of these
      infections are often related to biofilm formation. The objective of this study
      was to investigate the anti-biofilm activity of low-molecular weight chitosan
      hydrogel (LMWCH), a natural biopolymer obtained from the N-deacylation of
      crustacean chitin, upon clinical relevant Candida species. The in vitro ability
      of LMWCH to impair biofilm formation and to disorganize a preformed biofilm was
      tested in polystyrene microplates and quantified by the semi quantitative XTT
      assay and by the crystal violet assay. LMWCH in vivo efficacy as a coating for
      medical indwelling devices was evaluated for the first time for Candida
      parapsilosis, using a mouse subcutaneous foreign body model using polyurethane
      catheter segments. Scanning electron microscopy was used to access biofilm
      architecture after LMWCH treatment. We found that LMWCH efficiently impaired
      biofilm formation of all Candida species, also promoting biofilm disaggregation.
      Most importantly, LMWCH was able to significantly inhibit biofilm formation by C.
      parapsilosis in an in vivo catheter mouse model. SEM images showed biofilm
      collapsed cells compatible with membrane damage, suggesting that this could be
      one of the possible mechanisms underlying biofilm impairment. LMWCH revealed to
      be a promising compound for treatment of candidiasis or its prevention through
      medical device coating. 

PMID- 24013186
TI  - N-acetylation of etamicastat, a reversible dopamine-beta-hydroxylase inhibitor.
AB  - Etamicastat [(R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)
      thione hydrochloride] is a reversible dopamine-beta-hydroxylase inhibitor that
      decreases norepinephrine levels in sympathetically innervated tissues. After in
      vivo administration, N-acetylation of etamicastat was found to be a main
      metabolic pathway. The purpose of the current study was to characterize the N
      acetylation of etamicastat by N-acetyltransferases (NAT1 and NAT2) and evaluate
      potential species differences in etamicastat N-acetylation using a sensitive and
      specific liquid chromatography-mass spectrometry assay. Marked differences in
      etamicastat N-acetylation were observed among the laboratory species and humans.
      After oral administration, the rat, hamster, and human subjects presented the
      highest rates of etamicastat N-acetylation, whereas almost no acetylation was
      observed in the mouse, rabbit, minipig, and monkey and no acetylation was
      observed in the dog. In in vitro studies, rats and humans showed similar
      acetylation rates, whereas no acetylation was detected in the dog. Studies
      performed with human recombinant NAT1 4 and NAT2 4 enzymes revealed that both
      were able to conjugate etamicastat, although at different rates. NAT1 had lower
      affinity compared with NAT2 (Km, 124.8 +/- 9.031 uM and 17.14 +/- 3.577 uM,
      respectively). A significant correlation (r(2) = 0.65, P < 0.05) was observed in
      a comparison of etamicastat N-acetylation by human single-donor enzymes and
      sulfamethazine, a selective substrate to NAT2. No correlation was observed with p
      aminosalicylic acid, a NAT1 selective substrate. In conclusion, these results
      suggest that NAT2 and, to a lesser extent, NAT1 contribute to etamicastat N
      acetylation. Furthermore, the high interspecies and intraspecies differences in N
      acetylation should be taken into consideration when evaluating the in vivo
      bioavailability of etamicastat. 

PMID- 24013187
TI  - Two faces of attractiveness: making beauty in averageness appear and reverse.

PMID- 24013185
TI  - Tracking immune cells in vivo using magnetic resonance imaging.
AB  - The increasing complexity of in vivo imaging technologies, coupled with the
      development of cell therapies, has fuelled a revolution in immune cell tracking
      in vivo. Powerful magnetic resonance imaging (MRI) methods are now being
      developed that use iron oxide- and 19F-based probes. These MRI technologies can
      be used for image-guided immune cell delivery and for the visualization of immune
      cell homing and engraftment, inflammation, cell physiology and gene expression.
      MRI-based cell tracking is now also being applied to evaluate therapeutics that
      modulate endogenous immune cell recruitment and to monitor emerging cellular
      immunotherapies. These recent uses show that MRI has the potential to be
      developed in many applications to follow the fate of immune cells in vivo.

PMID- 24013188
TI  - Everyday empathic accuracy in younger and older couples: do you need to see your
      partner to know his or her feelings?
AB  - On average, older adults are less accurate than younger adults at recognizing
      emotions from faces or voices. We challenge the view that such differences in
      emotion-recognition tasks reflect differences in empathic accuracy (the ability
      to infer other people's feelings): Empathic accuracy relies not only on sensory
      cues (e.g., emotional expressions) but also on knowledge about the target person.
      Using smartphone-based measures, we assessed empathic accuracy in younger and
      older couples' daily lives and found that younger adults' empathic accuracy was
      higher than older adults' empathic accuracy when their partners were visibly
      present. During the partners' absence, however, when judgments relied exclusively
      on knowledge of those partners, no age differences emerged, and performance in
      both age groups was still more accurate than chance. We conclude that across
      adulthood, sensory information and knowledge differentially support empathic
      accuracy. Laboratory emotion-recognition tasks may therefore underestimate older
      adults' empathic competencies. 

PMID- 24013189
TI  - Blood pressure and cognitive function: the role of central aortic and brachial
      pressures.
AB  - Central (aortic) blood pressures differ from brachial pressures and may be more
      relevant to the study of cognitive function, given that blood is delivered to the
      brain through the central large arteries. Pulse-pressure amplification reflects
      the augmentation of blood pressure between the central and peripheral arteries,
      which diminishes with aging. We aimed to determine the association between
      central blood pressure and cognitive function in independently living adults aged
      20 to 82 years (N = 493). In adjusted regression models, higher central systolic
      pressure and higher central pulse pressure were each associated with poorer
      processing speed, Stroop processing, and recognition memory. Lower amplification
      was associated with poorer Stroop processing, working memory, and recognition
      memory. Higher brachial systolic pressure and brachial pulse pressure were both
      associated with poorer Stroop processing. In summary, central pressures and
      amplification were sensitive indicators of cognitive aging, predicting aspects of
      cognitive performance not predicted by brachial blood pressure. 

PMID- 24013191
TI  - A novel UPLC-ESI-MS/MS method for the quantitation of disulfiram, its role in
      stabilized plasma and its application.
AB  - Disulfiram (DSF) has been used to treat alcoholism for many years and it has been
      suggested to play a key role in combatting many kinds of tumors. However,
      disulfiram has complex pharmacokinetics and is rapidly eliminated which limits
      its use as a tumor treatment. Therefore, a rapid and sensitive analytical method
      based on ultra performance liquid chromatography coupled to electrospray
      ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) was developed and validated
      for the determination of disulfiram in rat plasma. Blood samples were pre
      stabilized with a stabilizing agent and then plasma was obtained and subjected to
      solid phase extraction (SPE), and chromatographed on a Phenomenex Kinetex((r)) XB
      C18 column with gradient elution using a mobile phase consisting of acetonitrile
      water (containing 0.1% formic acid and 1mM ammonium acetate) at a flow rate of
      0.2mL/min for 3min. Multiple reactions monitoring in positive mode was carried
      out with disulfiram at 296.95/115.94 and diphenhydramine (internal standard, IS)
      at 256.14/167.02 over a linear range from 0.6 to 1200ng/mL. The extraction
      recovery of disulfiram for different concentrations ranged from 75.7% to 78.3%.
      The intra- and inter-day precision was less than 8.93% and 12.39%, respectively,
      and the accuracy was within +/-7.75%. The validated method was successfully
      applied to a pharmacokinetic study of disulfiram in rat plasma after oral
      administration of a dose of 180mg/kg. 

PMID- 24013190
TI  - An LC-MS assay for the screening of cardiovascular medications in human samples.
AB  - Cardiovascular drugs are the most commonly prescribed medications. Some prior
      assays successfully detect cardiovascular drugs among multiple classes using a
      single sample. Here, we develop an assay to detect a broad range of
      cardiovascular drug classes to include commonly used cardiovascular drugs and
      evaluate the assay's analytical and statistical properties in a clinical setting.
      We describe a protocol for drug detection that encompasses 34 commonly prescribed
      cardiovascular drugs or drug metabolites with a single LC-MS/MS method using
      100MUL of serum or plasma. Drug classes monitored by this assay include:
      anticoagulants, angiotensin converting enzyme inhibitors (ACEI), angiotensin II
      receptor blockers (ARB), beta blockers, calcium channel blockers, diuretics,
      statins, and vasodilators, as well as digoxin, fenofibrate, and niacin.
      Analytical accuracy and precision for each drug were evaluated by repeating the
      assay on spiked samples at low, medium, and high concentrations. In 294 clinical
      samples obtained from hospitalized patients for whom medication administration
      was recorded, we evaluated the assay's statistical sensitivity, specificity, and
      accuracy. For the 34 drugs or drug metabolites, the assay was statistically
      sensitive (>0.90) for all drugs except captopril (0.25), isosorbide (0.81), and
      niacin (0.89). The assay was statistically specific for all drugs, with a minimum
      specificity of 0.94 (aspirin). To our knowledge, this method is the first method
      of simultaneous analysis of 34 cardiovascular drugs or drug metabolites from nine
      drug classes evaluated using clinical samples from hospitalized patients. 

PMID- 24013192
TI  - Ruthenium-catalyzed olefin metathesis accelerated by the steric effect of the
      backbone substituent in cyclic (alkyl)(amino) carbenes.
AB  - Three ruthenium complexes bearing backbone-monosubstituted CAACs were prepared
      and displayed dramatic improvement in catalytic efficiency not only in RCM
      reaction but also in the ethenolysis of methyl oleate, compared to those bearing
      backbone-disubstituted CAACs. 

PMID- 24013193
TI  - Characterization of the IncA/C plasmid pSCEC2 from Escherichia coli of swine
      origin that harbours the multiresistance gene cfr.
AB  - OBJECTIVES: To determine the complete nucleotide sequence of the multidrug
      resistance plasmid pSCEC2, isolated from a porcine Escherichia coli strain, and
      to analyse it with particular reference to the cfr gene region. METHODS: Plasmid
      pSCEC2 was purified from its E. coli J53 transconjugant and then sequenced using
      the 454 GS-FLX System. After draft assembly, predicted gaps were closed by PCR
      with subsequent sequencing of the amplicons. RESULTS: Plasmid pSCEC2 is 135 615
      bp in size and contains 200 open reading frames for proteins of >=100 amino
      acids. Analysis of the sequence of pSCEC2 revealed two resistance gene segments.
      The 4.4 kb cfr-containing segment is flanked by two IS256 elements in the same
      orientation, which are believed to be involved in the dissemination of the rRNA
      methylase gene cfr. The other segment harbours the resistance genes floR, tet(A)
      tetR, strA/strB and sul2, which have previously been found on other IncA/C
      plasmids. Except for these two resistance gene regions, the pSCEC2 backbone
      displayed >99% nucleotide sequence identity to that of other IncA/C family
      plasmids isolated in France, Chile and the USA. CONCLUSIONS: The cfr gene was
      identified on an IncA/C plasmid, which is well known for its broad host range and
      transfer and maintenance properties. The location on such a plasmid will further
      accelerate the dissemination of cfr and co-located resistance genes among
      different Gram-negative bacteria. The genetic context of cfr on plasmid pSCEC2
      underlines the complexity of cfr transfer events and confirms the role that
      insertion sequences play in the spread of cfr.

PMID- 24013194
TI  - An ST405 NDM-4-producing Escherichia coli isolated from a Danish patient
      previously hospitalized in Vietnam.

PMID- 24013195
TI  - High prevalence of beta-lactam and macrolide resistance genes in human oral
      Capnocytophaga species.
AB  - OBJECTIVES: To determine macrolide-lincosamide-streptogramin (MLS) resistance
      determinants in the Capnocytophaga genus and to describe the prevalence of beta
      lactam resistance genes in human oral Capnocytophaga species. METHODS: Forty
      eight Capnocytophaga isolates identified by analysis of 16S rRNA sequences were
      isolated from subgingival samples from 14 haematology patients (HPs), 11
      periodontitis patients (PPs) and 17 healthy volunteers (HVs). MICs of beta-lactam
      and MLS antibiotics were obtained for all isolates. blaCfxA, blaCSP-1 (encoding a
      new class A beta-lactamase) and MLS resistance genes [erm(F), erm(B), erm(Q),
      erm(D), erm(C) and erm(A)] were evaluated using specific PCR and sequencing.
      RESULTS: In HVs, which had the lowest prevalence of beta-lactamase-producing
      isolates in comparison with the other groups (16%; P < 0.001), Capnocytophaga
      ochracea was the prominent species (68%; P < 0.03). In PPs, which had a high
      prevalence of beta-lactamase-positive isolates (82%; P < 0.001), Capnocytophaga
      sputigena was more frequently identified (64%; P < 0.03). In HPs, 50% of isolates
      were beta-lactamase-positive. The more rarely identified species (15%)
      Capnocytophaga gingivalis, Capnocytophaga granulosa and Capnocytophaga
      leadbetteri were isolated only from PPs and/or HPs. All beta-lactam-resistant
      isolates (44%) were PCR-positive for blaCfxA (31%) or blaCSP-1 (12.5%).
      Interestingly, blaCSP-1 was identified only in a subgroup of the C. sputigena
      species. Twenty-nine percent of isolates were MLS resistant independently of
      species identification, beta-lactamase production or patient group. The MLS
      resistant isolates carried the erm(F) or erm(C) gene (93% and 7%, respectively),
      previously unknown in the Capnocytophaga genus. CONCLUSIONS: Our findings
      illustrate that Capnocytophaga species are important contributors to the beta
      lactam and MLS resistance gene reservoir in the oral microbiome.

PMID- 24013196
TI  - Accelerating the design of biomimetic materials by integrating RNA-seq with
      proteomics and materials science.
AB  - Efforts to engineer new materials inspired by biological structures are hampered
      by the lack of genomic data from many model organisms studied in biomimetic
      research. Here we show that biomimetic engineering can be accelerated by
      integrating high-throughput RNA-seq with proteomics and advanced materials
      characterization. This approach can be applied to a broad range of systems, as we
      illustrate by investigating diverse high-performance biological materials
      involved in embryo protection, adhesion and predation. In one example, we rapidly
      engineer recombinant squid sucker ring teeth proteins into a range of structural
      and functional materials, including nanopatterned surfaces and photo-cross-linked
      films that exceed the mechanical properties of most natural and synthetic
      polymers. Integrating RNA-seq with proteomics and materials science facilitates
      the molecular characterization of natural materials and the effective translation
      of their molecular designs into a wide range of bio-inspired materials. 

PMID- 24013199
TI  - Co(3)O(4) microspheres with free-standing nanofibers for high performance non
      enzymatic glucose sensor.
AB  - Co3O4 microspheres with free-standing or bundled nanofibers (NFs) were fabricated
      for use as a platform for non-enzymatic glucose sensing. The sensor based on free
      standing Co3O4 NFs displays enhanced sensitivity (1440 MUA mM(-1) cm(-2)), a
      wider linear range (0.005-12 mM) and superior selectivity. The application of
      this glucose sensor in human blood serum has also been demonstrated successfully.

PMID- 24013198
TI  - Locus-specific editing of histone modifications at endogenous enhancers.
AB  - Mammalian gene regulation is dependent on tissue-specific enhancers that can act
      across large distances to influence transcriptional activity. Mapping experiments
      have identified hundreds of thousands of putative enhancers whose functionality
      is supported by cell type-specific chromatin signatures and striking enrichments
      for disease-associated sequence variants. However, these studies did not address
      the in vivo functions of the putative elements or their chromatin states and did
      not determine which genes, if any, a given enhancer regulates. Here we present a
      strategy to investigate endogenous regulatory elements by selectively altering
      their chromatin state using programmable reagents. Transcription activator-like
      (TAL) effector repeat domains fused to the LSD1 histone demethylase efficiently
      remove enhancer-associated chromatin modifications from target loci, without
      affecting control regions. We find that inactivation of enhancer chromatin by
      these fusion proteins frequently causes downregulation of proximal genes,
      revealing enhancer target genes. Our study demonstrates the potential of
      epigenome editing tools to characterize an important class of functional genomic
      elements. 

PMID- 24013197
TI  - Modified mRNA directs the fate of heart progenitor cells and induces vascular
      regeneration after myocardial infarction.
AB  - In a cell-free approach to regenerative therapeutics, transient application of
      paracrine factors in vivo could be used to alter the behavior and fate of
      progenitor cells to achieve sustained clinical benefits. Here we show that
      intramyocardial injection of synthetic modified RNA (modRNA) encoding human
      vascular endothelial growth factor-A (VEGF-A) results in the expansion and
      directed differentiation of endogenous heart progenitors in a mouse myocardial
      infarction model. VEGF-A modRNA markedly improved heart function and enhanced
      long-term survival of recipients. This improvement was in part due to
      mobilization of epicardial progenitor cells and redirection of their
      differentiation toward cardiovascular cell types. Direct in vivo comparison with
      DNA vectors and temporal control with VEGF inhibitors revealed the greatly
      increased efficacy of pulse-like delivery of VEGF-A. Our results suggest that
      modRNA is a versatile approach for expressing paracrine factors as cell fate
      switches to control progenitor cell fate and thereby enhance long-term organ
      repair. 

PMID- 24013200
TI  - Structural transformations in Pb/Si(111) phases induced by C60 adsorption.
AB  - Structural transformations at the Pb/Si(111) surface occurring upon C60
      adsorption onto Pb/Si(111)1 * 1 phase at room temperature and Pb/Si(111)[Formula:
      see text] at low temperatures between 30 and 210 K, have been studied using
      scanning tunneling microscopy and low-energy electron diffraction observations.
      Typically, C60 fullerenes agglomerate into random molecular islands nucleated at
      the surface defects. C60 island formation is accompanied by expelling Pb atoms to
      the surrounding surface area where more dense Pb/Si(111) phases form.
      Productivity of C60-induced expelling of Pb atoms is controlled by surface
      defects and is suppressed dramatically when regular ('crystalline') C60 islands
      self-assemble at the defect-free Pb/Si(111) surface. When Pb atoms are ejected by
      the random C60 islands, extended structural transformations involving reordering
      of numerous Pb atoms are fully completed at the surface within the shortest
      possible time (a few dozen seconds) to reapproach and image the surface after C60
      deposition. Estimations show that the observed transformations cannot be
      controlled by random walk diffusion of Pb adatoms, which implies a highly
      correlated motion of the Pb atom displacements within the layer.

PMID- 24013201
TI  - Obesity and mortality risk: new findings from body mass index trajectories.
AB  - Little research has addressed the heterogeneity and mortality risk in body mass
      index (BMI) trajectories among older populations. Applying latent class
      trajectory models to 9,538 adults aged 51 to 77 years from the US Health and
      Retirement Study (1992-2008), we defined 6 latent BMI trajectories: normal weight
      downward, normal weight upward, overweight stable, overweight obesity, class I
      obese upward, and class II/III obese upward. Using survival analysis, we found
      that people in the overweight stable trajectory had the highest survival rate,
      followed by those in the overweight obesity, normal weight upward, class I obese
      upward, normal weight downward, and class II/III obese upward trajectories. The
      results were robust after controlling for baseline demographic and socioeconomic
      characteristics, smoking status, limitations in activities of daily living, a
      wide range of chronic illnesses, and self-rated health. Further analysis
      suggested that BMI trajectories were more predictive of mortality risk than was
      static BMI status. Using attributable risk analysis, we found that approximately
      7.2% of deaths after 51 years of age among the 1931-1941 birth cohort were due to
      class I and class II/III obese upward trajectories. This suggests that
      trajectories of increasing obesity past 51 years of age pose a substantive threat
      to future gains in life expectancy. 

PMID- 24013202
TI  - Association of antepartum and postpartum depression in Ghanaian and Ivorian women
      with febrile illness in their offspring: a prospective birth cohort study.
AB  - In low-income countries, perinatal depression is common, but longitudinal data on
      its influence on child health are rare. We examined the association between
      maternal depression and febrile illness in children. There were 654 mother/child
      dyads in Ghana and Cote d'Ivoire that were enrolled in a prospective birth cohort
      in 2010-2011 and underwent 2-years of follow up. Mothers were examined for
      depression using the Patient Health Questionnaire depression module antepartum
      and 3 and 12 months postpartum. The hazard of febrile illness in children of
      depressed and nondepressed mothers was estimated using a recurrent event Cox
      proportional hazards model. The prevalences of antepartum depression in mothers
      from Cote d'Ivoire and Ghana were 28.3% and 26.3%, respectively. The prevalences
      of depression at 3 and 12 months postpartum were 11.8% and 16.1% (Cote d'Ivoire)
      and 8.9% and 7.2% (Ghana). The crude and adjusted (for country and socioeconomic
      status) hazard ratios of febrile illness in children of depressed mothers
      compared with those in children of nondepressed mothers were 1.57 (95% confidence
      interval: 1.20, 2.07) and 1.32 (95% confidence interval: 1.01, 1.74)
      respectively. Perinatal depression was frequent and associated with febrile
      illness in the offspring. Our results showed that a high prevalence of depression
      in sub-Saharan Africa may pose a serious public health threat to women and their
      offspring.

PMID- 24013203
TI  - A new self-controlled case series method for analyzing spontaneous reports of
      adverse events after vaccination.
AB  - In this paper, we propose new methods for analyzing cases of vaccine adverse
      events spontaneously reported to a surveillance database. The methods use the
      self-controlled case series approach, extended in several ways with parametric
      and nonparametric assumptions to account for the specific features of the data
      (large amount of underreporting and variation of reporting with time since
      vaccination). This work was motivated by the documented risk of intussusception
      after RotaShield vaccination (Wyeth-Lederle Vaccines, Radnor, Pennsylvania) and
      used worldwide spontaneous reports of intussusception occurring after Rotarix
      vaccination (GlaxoSmithKline Biologics, Research Triangle Park, North Carolina)
      collected between January 2004 and February 2010. The estimated risk during the 3
      to 7-day period after vaccination was approximately 5 times higher after dose 1
      of Rotarix than after dose 2, which is similar to published findings on the same
      topic. We undertook a large simulation study to evaluate the performance of the
      method in different scenarios, including its robustness to different sample sizes
      and time-dependent reporting functions. The bias was generally small, the type I
      error rate was correctly controlled, and the power to detect a risk ratio of 4
      was satisfactory, provided that the sample size was over 100. The proposed
      methods are an effective way to explore and quantify vaccine safety signals from
      spontaneous reports. 

PMID- 24013204
TI  - Using pneumococcal carriage data to monitor postvaccination changes in invasive
      disease.
AB  - Pneumococcal conjugate vaccines (PCVs) have been introduced worldwide. However,
      few developing countries have high-quality surveillance systems available for
      monitoring vaccine impact. We evaluated whether data from nasopharyngeal carriage
      studies can be used to accurately monitor post-PCV changes in the incidence of
      invasive pneumococcal disease (IPD) among children under 5 years of age. For
      various dates during 1991-2010, data on nasopharyngeal pneumococcal carriage and
      on IPD before and after administration of 7-valent PCV (PCV7) were available from
      England and Wales, the Netherlands, the Navajo and White Mountain Apache American
      Indian populations, and the US states of Massachusetts and Alaska. We estimated
      the change in carriage prevalence for each serotype in each study and then either
      calculated the average change (inverse variance-weighted) among vaccine and
      nonvaccine serotypes (model 1) or used mixed-effects models to estimate the
      change for each serotype individually, pooling serotype data within or between
      studies (models 2 and 3). We then multiplied these values by the proportion of
      IPD caused by each serotype during the pre-PCV7 period to obtain an estimate of
      post-PCV7 disease incidence. Model 1 accurately captured overall changes in IPD
      incidence following PCV7 introduction for most studies, while the more detailed
      models, models 2 and 3, were less accurate. Carriage data can be used in this
      simple model to estimate post-PCV changes in IPD incidence.

PMID- 24013205
TI  - Reconstitution of the 26S proteasome reveals functional asymmetries in its AAA+
      unfoldase.
AB  - The 26S proteasome is the major eukaryotic ATP-dependent protease, yet the
      detailed mechanisms used by the proteasomal heterohexameric AAA+ unfoldase to
      drive substrate degradation remain poorly understood. To perform systematic
      mutational analyses of individual ATPase subunits, we heterologously expressed
      the unfoldase subcomplex from Saccharomyces cerevisiae in Escherichia coli and
      reconstituted the proteasome in vitro. Our studies demonstrate that the six
      ATPases have distinct roles in degradation, corresponding to their positions in
      the spiral staircases adopted by the AAA+ domains in the absence or presence of
      substrate. ATP hydrolysis in subunits at the top of the staircases is critical
      for substrate engagement and translocation. Whereas the unfoldase relies on this
      vertical asymmetry for substrate processing, interaction with the peptidase
      exhibits three-fold symmetry with contributions from alternate subunits. These
      diverse functional asymmetries highlight how the 26S proteasome deviates from
      simpler, homomeric AAA+ proteases. 

PMID- 24013206
TI  - A cancer-associated BRCA2 mutation reveals masked nuclear export signals
      controlling localization.
AB  - Germline missense mutations affecting a single BRCA2 allele predispose humans to
      cancer. Here we identify a protein-targeting mechanism that is disrupted by the
      cancer-associated mutation, BRCA2(D2723H), and that controls the nuclear
      localization of BRCA2 and its cargo, the recombination enzyme RAD51. A nuclear
      export signal (NES) in BRCA2 is masked by its interaction with a partner protein,
      DSS1, such that point mutations impairing BRCA2-DSS1 binding render BRCA2
      cytoplasmic. In turn, cytoplasmic mislocalization of mutant BRCA2 inhibits the
      nuclear retention of RAD51 by exposing a similar NES in RAD51 that is usually
      obscured by the BRCA2-RAD51 interaction. Thus, a series of NES-masking
      interactions localizes BRCA2 and RAD51 in the nucleus. Notably, BRCA2(D2723H)
      decreases RAD51 nuclear retention even when wild-type BRCA2 is also present. Our
      findings suggest a mechanism for the regulation of the nucleocytoplasmic
      distribution of BRCA2 and RAD51 and its impairment by a heterozygous disease
      associated mutation. 

PMID- 24013207
TI  - Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence.
AB  - Although telomeres are heterochromatic, they are transcribed into noncoding
      telomeric repeat-containing RNA (TERRA). Here we show that RNA-DNA hybrids form
      at telomeres and are removed by RNase H enzymes in the budding yeast,
      Saccharomyces cerevisiae. In recombination-competent telomerase mutants,
      telomeric RNA-DNA hybrids promote recombination-mediated elongation events that
      delay the onset of cellular senescence. Reduction of TERRA and telomeric RNA-DNA
      hybrid levels diminishes rates of recombination-mediated telomere elongation in
      cis. Overexpression of RNase H decreases telomere recombination rates and
      accelerates senescence in recombination-competent but not recombination-deficient
      cells. In contrast, in the absence of both telomerase and homologous
      recombination, accumulation of telomeric RNA-DNA hybrids leads to telomere loss
      and accelerated rates of cellular senescence. Therefore, the regulation of TERRA
      transcription and telomeric RNA-DNA-hybrid formation are important determinants
      of both telomere-length dynamics and proliferative potential after the
      inactivation of telomerase. 

PMID- 24013208
TI  - Structure of a pseudokinase-domain switch that controls oncogenic activation of
      Jak kinases.
AB  - The V617F mutation in the Jak2 pseudokinase domain causes myeloproliferative
      neoplasms, and the equivalent mutation in Jak1 (V658F) is found in T-cell
      leukemias. Crystal structures of wild-type and V658F-mutant human Jak1
      pseudokinase reveal a conformational switch that remodels a linker segment
      encoded by exon 12, which is also a site of mutations in Jak2. This switch is
      required for V617F-mediated Jak2 activation and possibly for physiologic Jak
      activation. 

PMID- 24013209
TI  - Crystal structure of a substrate-free aspartate transporter.
AB  - Archaeal glutamate transporter homologs catalyze the coupled uptake of aspartate
      and three sodium ions. After the delivery of the substrate and sodium ions to the
      cytoplasm, the empty binding site must reorient to the outward-facing
      conformation to reset the transporter. Here, we report a crystal structure of the
      substrate-free transporter GltTk from Thermococcus kodakarensis, which provides
      insight into the mechanism of this essential step in the translocation cycle. 

PMID- 24013210
TI  - Provider dismissal of vaccine-hesitant families: misguided policy that fails to
      benefit children.
AB  - Some health care providers have adopted the policy of refusing to accept into
      their practices families who refuse to vaccinate their children according to the
      standard vaccine schedule. While the frustration that drives these policies is
      understandable, the practice of refusing to see these families is misguided. Such
      a strategy does not benefit the child or the health of the community, and may
      have a negative impact on both. Physicians represent the best opportunity to
      influence the vaccine-hesitant parent, but only if physicians are willing to care
      for these families will that be possible. Maintaining a relationship of open
      communication and trust remains the best strategy for addressing the problem of
      parental vaccine hesitancy. 

PMID- 24013212
TI  - Novel paper-based cholesterol biosensor using
      graphene/polyvinylpyrrolidone/polyaniline nanocomposite.
AB  - A novel nanocomposite of graphene (G), polyvinylpyrrolidone (PVP) and polyaniline
      (PANI) has been successfully prepared and used for the modification of paper
      based biosensors via electrospraying. The droplet-like nanostructures of
      G/PVP/PANI-modified electrodes are obtained with an average size of 160 +/- 1.02
      nm. Interestingly, the presence of small amount of PVP (2 mg mL(-1)) in the
      nanocomposites can substantially improve the dispersibility of G and increase the
      electrochemical conductivity of electrodes, leading to enhanced sensitivity of
      the biosensor. The well-defined cyclic voltammogram of standard
      ferri/ferrocyanide is achieved on a G/PVP/PANI-modified electrode with a 3-fold
      increase in the current signal compared to an unmodified electrode. This modified
      electrode also exhibits excellent electrocatalytic activity towards the oxidation
      of hydrogen peroxide (H2O2). Furthermore, cholesterol oxidase (ChOx) is attached
      to G/PVP/PANI-modified electrode for the amperometric determination of
      cholesterol. Under optimum conditions, a linear range of 50 MUM to 10mM is
      achieved and the limit of detection is found to be 1 MUM for cholesterol.
      Finally, the proposed system can be applied for the determination of cholesterol
      in a complex biological fluid (i.e. human serum).

PMID- 24013211
TI  - Impact of elevated plasma serotonin on global gene expression of murine
      megakaryocytes.
AB  - BACKGROUND: Serotonin (5-HT) is a biogenic amine that also acts as a mitogen and
      a developmental signal early in rodent embryogenesis. Genetic and pharmacological
      disruption of 5-HT signaling causes various diseases and disorders via mediating
      central nervous system, cardiovascular system, and serious abnormalities on a
      growing embryo. Today, neither the effective modulators on 5-HT signaling
      pathways nor the genes affected by 5-HT signal are well known yet.
      METHODOLOGY/PRINCIPAL FINDINGS: In an attempt to identify the genes altered by 5
      HT signaling pathways, we analyzed the global gene expression via the Illumina
      array platform using the mouse WG-6 v2.0 Expression BeadChip containing 45,281
      probe sets representing 30,854 genes in megakaryocytes isolated from mice infused
      with 5-HT or saline. We identified 723 differentially expressed genes of which
      706 were induced and 17 were repressed by elevated plasma 5-HT.
      CONCLUSIONS/SIGNIFICANCE: Hierarchical gene clustering analysis was utilized to
      represent relations between groups and clusters. Using gene ontology mining tools
      and canonical pathway analyses, we identified multiple biological pathways that
      are regulated by 5-HT: (i) cytoskeletal remodeling, (ii) G-protein signaling,
      (iii) vesicular transport, and (iv) apoptosis and survival. Our data encompass
      the first extensive genome-wide based profiling in the progenitors of platelets
      in response to 5-HT elevation in vivo.

PMID- 24013213
TI  - Co-evolutionary dynamics of the bacteria Vibrio sp. CV1 and phages V1G, V1P1, and
      V1P2: implications for phage therapy.
AB  - Bacterial infections are the second largest cause of mortality in shrimp
      hatcheries. Among them, bacteria from the genus Vibrio constitute a major threat.
      As the use of antibiotics may be ineffective and banned from the food sector,
      alternatives are required. Historically, phage therapy, which is the use of
      bacteriophages, is thought to be a promising option to fight against bacterial
      infections. However, as for antibiotics, resistance can be rapidly developed.
      Since the emergence of resistance is highly undesirable, a formal
      characterization of the dynamics of its acquisition is mandatory. Here, we
      explored the co-evolutionary dynamics of resistance between the bacteria Vibrio
      sp. CV1 and the phages V1G, V1P1, and V1P2. Single-phage treatments as well as a
      cocktail composed of the three phages were considered. We found that in the
      presence of a single phage, bacteria rapidly evolved resistance, and the phages
      decreased their infectivity, suggesting that monotherapy may be an inefficient
      treatment to fight against Vibrio infections in shrimp hatcheries. On the
      contrary, the use of a phage cocktail considerably delayed the evolution of
      resistance and sustained phage infectivity for periods in which shrimp larvae are
      most susceptible to bacterial infections, suggesting the simultaneous use of
      multiple phages as a serious strategy for the control of vibriosis. These
      findings are very promising in terms of their consequences to different
      industrial and medical scenarios where bacterial infections are present. 

PMID- 24013214
TI  - A general fluorescent sensor design strategy for "turn-on" activity detection of
      exonucleases and restriction endonucleases based on graphene oxide.
AB  - Using graphene oxide (GO) as a nanoquencher, a universal sensor design strategy
      was developed on the basis of significantly different binding affinities of GO to
      single-stranded DNAs (ss-DNAs) with different lengths. The proposed sensors could
      be used for the activity detection of both exonucleases and restriction
      endonucleases. To achieve this, a single-labeled fluorescent oligonucleotide
      probe, which had a single-stranded structure or a hairpin structure with a long
      single-stranded loop, was used. Such a probe could be efficiently absorbed on the
      surface of GO, resulting in the quenching of the fluorescent signal. Excision of
      the single-stranded probe by exonucleases or site-specific cleavage at the double
      stranded stem of the hairpin probe by restriction endonuclease released
      fluorophore-labeled nucleotide, which could not be efficiently absorbed by GO,
      thus leading to increase in fluorescence of the corresponding sensing system. As
      examples, three sensors, which were used for activity detection of the
      exonuclease Exo 1 and the restriction endonucleases EcoR I and Hind III, were
      developed. These three sensors could specifically and sensitively detect the
      activities of Exo 1, EcoR I and Hind III with detection limits of 0.03 U mL(-1),
      0.06 U mL(-1) and 0.04 U mL(-1), respectively. Visual detection was also
      possible. 

PMID- 24013215
TI  - Mast cells in the human dura: effects of age and dural bleeding.

PMID- 24013216
TI  - CSF complications following intradural spinal surgeries in children.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) leakage is a complication of intradural
      spinal surgery and is associated with poor wound healing and infection. The
      incidence of CSF leak is reported at ~16% in adults, but little information is
      available in children. PURPOSE: The aim of this study is to determine the CSF
      leak rate and predisposing factors after intradural pediatric spinal surgeries.
      METHODS: This study was a retrospective chart review of 638 intradural spinal
      operations at BC Children's Hospital. CSF leak was defined as pseudomeningocele
      or CSF leak through incision. Primary operations to untether
      lipomyelomeningoceles, myelomeningocele/meningocele closure, and Chiari
      decompressions were excluded. RESULTS: CSF leaks occurred in 7.1%, with 3% having
      overt CSF leaks through skin (OCSF leak). CSF leaks, specifically OCSF leaks,
      were associated with postoperative wound infection (P = 0.0016). Sixteen of 45
      cases of CSF leak required reoperation. The type of dural suture used, site of
      operation, or use of fibrin glue did not affect CSF leak rates. Previous spinal
      surgery (P < 0.0001), use of dural graft (P = 0.0043), method of dural suturing
      (P = 0.0023), and procedure performed (P < 0.001) were associated with
      postoperative CSF leakage. Patients with CSF leak were older than those without
      leak (98 vs. 72 months, P = 0.002). CONCLUSIONS: Our results provide evidence on
      intraoperative factors that may predispose to CSF leaks after spinal intradural
      surgery and may help guide surgical practice. This study confirms that the
      pediatric population shares many of the same risk factors for CSF leak as in
      adult populations. Further research is needed to explain how specific factors are
      associated with CSF leaks.

PMID- 24013217
TI  - SON connects the splicing-regulatory network with pluripotency in human embryonic
      stem cells.
AB  - Human embryonic stem cells (hESCs) harbour the ability to undergo lineage
      specific differentiation into clinically relevant cell types. Transcription
      factors and epigenetic modifiers are known to play important roles in the
      maintenance of pluripotency of hESCs. However, little is known about regulation
      of pluripotency through splicing. In this study, we identify the spliceosome
      associated factor SON as a factor essential for the maintenance of hESCs.
      Depletion of SON in hESCs results in the loss of pluripotency and cell death.
      Using genome-wide RNA profiling, we identified transcripts that are regulated by
      SON. Importantly, we confirmed that SON regulates the proper splicing of
      transcripts encoding for pluripotency regulators such as OCT4, PRDM14, E4F1 and
      MED24. Furthermore, we show that SON is bound to these transcripts in vivo. In
      summary, we connect a splicing-regulatory network for accurate transcript
      production to the maintenance of pluripotency and self-renewal of hESCs. 

PMID- 24013218
TI  - Regulation of PIK3C3/VPS34 complexes by MTOR in nutrient stress-induced
      autophagy.
AB  - Autophagy is a cellular defense response to stress conditions, such as nutrient
      starvation. The type III phosphatidylinositol (PtdIns) 3-kinase, whose catalytic
      subunit is PIK3C3/VPS34, plays a critical role in intracellular membrane
      trafficking and autophagy induction. PIK3C3 forms multiple complexes and the
      ATG14-containing PIK3C3 is specifically involved in autophagy induction.
      Mechanistic target of rapamycin (MTOR) complex 1, MTORC1, is a key cellular
      nutrient sensor and integrator to stimulate anabolism and inhibit catabolism.
      Inactivation of TORC1 by nutrient starvation plays a critical role in autophagy
      induction. In this report we demonstrated that MTORC1 inactivation is critical
      for the activation of the autophagy-specific (ATG14-containing) PIK3C3 kinase,
      whereas it has no effect on ATG14-free PIK3C3 complexes. MTORC1 inhibits the
      PtdIns 3-kinase activity of ATG14-containing PIK3C3 by phosphorylating ATG14,
      which is required for PIK3C3 inhibition by MTORC1 both in vitro and in vivo. Our
      data suggest a mechanistic link between amino acid starvation and autophagy
      induction via the direct activation of the autophagy-specific PIK3C3 kinase.

PMID- 24013219
TI  - Identification of prognostic immunophenotypic features in cancer stromal cells of
      high-grade neuroendocrine carcinomas of the lung.
AB  - PURPOSE: The immunophenotypes of cancer stromal cells have been recognized as
      prognostic factors of cancer. The purpose of this study was to analyze the
      prognostic markers of high-grade neuroendocrine carcinomas of the lung (HGNEC;
      both small cell carcinoma and large cell neuroendocrine carcinoma) by examining
      the immunophenotypes of cancer stromal cells. MATERIALS AND METHODS: One hundred
      and fifteen patients who underwent a complete resection of HGNEC were included in
      this study. We examined the presence of CD204-positive tumor-associated
      macrophages (TAMs), Foxp3-positive regulatory T cells (Tregs), and podoplanin
      positive cancer-associated fibroblasts (CAFs) to evaluate the prognostic values
      of these markers. RESULTS: The number of CD204-positive TAMs and Foxp3-positive
      Tregs did not influence the overall survival (OS) or the relapse-free survival
      (RFS) of the patients. However, patients with podoplanin-positive CAFs had a
      significantly better prognosis than those with podoplanin-negative CAFs [OS: p =
      0.002, RFS: p = 0.002, 5-year overall survival (5YR): 74 vs. 45 %]. According to
      subgroup analyses, patients with podoplanin-positive CAFs displayed a better
      prognosis for both small cell carcinoma (OS: p = 0.046, 5YR: 74 vs. 46 %) and
      large cell neuroendocrine carcinoma (OS: p = 0.020, 5YR: 74 vs. 45 %). Moreover,
      in multivariate analyses, the podoplanin status of the CAFs was shown to be a
      statistically significant independent predictor of recurrence. CONCLUSION: The
      presence of podoplanin-positive CAFs had a favorable prognostic value, suggesting
      that the evaluation of podoplanin expression by CAFs would lead to a novel risk
      classification of patients.

PMID- 24013221
TI  - Immobilized humic substances as redox mediator for the simultaneous removal of
      phenol and Reactive Red 2 in a UASB reactor.
AB  - The present study reports a novel treatment concept combining the redox-mediating
      capacity of immobilized humic substances with the biodegrading activity of
      anaerobic sludge for the simultaneous removal of two representative pollutants of
      textile wastewaters (e.g., phenol and Reactive Red 2 (RR2)) in a high-rate
      anaerobic reactor. The use of immobilized humic substances (1 g total organic
      carbon (TOC) L(-1), supported on an anion exchange resin) in an upflow anaerobic
      sludge blanket (UASB) reactor increased the decolorization efficiency of RR2 (~90
      %), extent of phenol oxidation (~75 %), and stability as compared to a control
      UASB reactor operated without immobilized humic substances, which collapsed after
      120 days of dye introduction (50-100 mg L(-1)). Increase in the concentration of
      immobilized humic substances (2 g TOC L(-1)) further enhanced the stability and
      efficiency of the UASB reactor. Detection of aniline in the effluent as RR2
      reduction product confirmed that reduction of RR2 was the major mechanism of dye
      removal. This is the first demonstration of immobilized humic substances serving
      as effective redox mediators for the removal of recalcitrant pollutants from
      wastewater in a high-rate anaerobic bioreactor. The novel treatment concept could
      also be applicable to remove a wide variety of contaminants susceptible to redox
      conversion, which are commonly found in different industrial sectors.

PMID- 24013220
TI  - Regulation of rat intrapulmonary arterial tone by arachidonic acid and
      prostaglandin E2 during hypoxia.
AB  - AIMS: Arachidonic acid (AA) and its metabolites, prostaglandins (PG) are known to
      be involved in regulation of vascular homeostasis including vascular tone and
      vessel wall tension, but their potential role in Hypoxic pulmonary
      vasoconstriction (HPV) remains unclear. In this study, we examined the effects of
      AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries
      (IPAs). METHODS AND RESULTS: We carried out the investigation on IPAs by vessel
      tension measurement. Isotetrandrine (20 uM) significantly inhibited phase I,
      phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 uM)
      and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and
      phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic
      response of rat IPAs. PGE2 alone caused a significant vasoconstriction in
      isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L
      161982 (1 uM) significantly inhibited phase I, phase IIb and phase IIc of hypoxic
      vasoconstriction. However, AH6809 (3 uM), an antagonist of EP1, EP2, EP3 and DP1
      receptors, exerted no effect on KPSS or hypoxia induced vessel contraction.
      Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced
      vessel contraction and abolish phase I, phase II b and phase II c of HPV.
      CONCLUSION: Our results demonstrated a vasoconstrictive effect of PGE2 on rat
      IPAs and this effect is via activation of EP4. Furthermore, our results suggest
      that intracellular cAMP plays dual roles in regulation of vascular tone,
      depending on the spatial distribution of cAMP and its coupling with EP receptor
      and Ca(2+) channels.

PMID- 24013222
TI  - Lipopeptides, a novel protein, and volatile compounds contribute to the
      antifungal activity of the biocontrol agent Bacillus atrophaeus CAB-1.
AB  - Bacillus atrophaeus CAB-1 displays a high inhibitory activity against various
      fungal pathogens and suppresses cucumber powdery mildew and tomato gray mold. We
      extracted and identified lipopeptides and secreted proteins and volatile
      compounds produced by strain CAB-1 to investigate the mechanisms involved in its
      biocontrol performance. In vitro assays indicated all three types of products
      contributed to the antagonistic activity against the fungal pathogen Botrytis
      cinerea. Each of these components also effectively prevented the occurrence of
      the cucumber powdery mildew caused by Sphaerotheca fuliginea under greenhouse
      conditions. Matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry revealed that the major bioactive lipopeptide was fengycin A (C15
      C17). We isolated the crude-secreted proteins of CAB-1 and purified a fraction
      with antifungal activity. This protein sequence shared a high identity with a
      putative phage-related pre-neck appendage protein, which has not been reported as
      an antifungal factor. The volatile compounds produced by CAB-1 were complex,
      including a range of alcohols, phenols, amines, and alkane amides. O-anisaldehyde
      represented one of the most abundant volatiles with the highest inhibition on the
      mycelial growth of B. cinerea. To our knowledge, this is the first report on
      profiling three types of antifungal substances in Bacilli and demonstrating their
      contributions to plant disease control.

PMID- 24013223
TI  - Mutations in 3'-long terminal repeat of HERV-W family in chromosome 7 upregulate
      syncytin-1 expression in urothelial cell carcinoma of the bladder through
      interacting with c-Myb.
AB  - Human endogenous retrovirus (HERV) accounts for ~8% of the human genome. Recent
      studies have reported that multiple HERV genes and long terminal repeats (LTRs)
      are involved in human tumorigenesis. Here we demonstrated that HERV-W env
      (syncytin-1) was overexpressed in 75.6% (62/82) of urothelial cell carcinoma
      (UCC) tissues of the bladder compared with only 6.1% (5/82) of matched tumor
      adjacent tissues (P<0.001). Syncytin-1 overexpression increased proliferation and
      viability of immortalized human uroepithelial cells. Colony-formation experiments
      and in-vivo tumor xenografts suggested that syncytin-1 overexpression had
      oncogenic potential. Syncytin-1 3'-LTR mutations (142T>C and 277A>G) were present
      in 87.8% (72/82) of UCC tissues. Normal 3'-LTR was found in 12.2% (10/82) of UCC
      tissues compared with 95.1% (78/82) of matched tumor-adjacent tissues (P<0.001).
      Interestingly, 3'-LTR mutations were significantly associated with syncytin-1
      overexpression. Luciferase assay and expression analysis revealed that 3'-LTR
      mutations, especially the 142T>C mutation, enhanced the syncytin-1 promoter
      activity and expression. In-silico analysis, electrophoretic mobility shift
      assays and chromatin immunoprecipitation assays demonstrated the binding of c-Myb
      to 3'-LTRs when the mutations occurred. This alternative interaction was found to
      be dependent on 142T>C mutation. C-Myb activated syncytin-1 promoter activity and
      expression by binding to mutant 3'-LTRs. Taken together, these data indicate that
      syncytin-1 overexpression may be an indicator of UCC risk. The 3'-LTR mutations
      may upregulate syncytin-1 expression, enabling it to participate in UCC
      tumorigenesis and development by interacting with c-Myb.

PMID- 24013224
TI  - Inhibition of the mitochondrial pyrimidine biosynthesis enzyme dihydroorotate
      dehydrogenase by doxorubicin and brequinar sensitizes cancer cells to TRAIL
      induced apoptosis.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      agent in selectively killing tumor cells. However, TRAIL monotherapy has not been
      successful as many cancer cells are resistant to TRAIL. Chemotherapeutic agents,
      such as doxorubicin have been shown to act synergistically with TRAIL, but the
      exact mechanisms of actions are poorly understood. In this study, we performed
      high-throughput small interfering RNA screening and genome-wide gene expression
      profiling on doxorubicin-treated U1690 cells to explore novel mechanisms
      underlying doxorubicin-TRAIL synergy. The screening and expression profiling
      results were integrated and dihydroorotate dehydrogenase (DHODH) was identified
      as a potential candidate. DHODH is the rate-limiting enzyme in the pyrimidine
      synthesis pathway, and its expression was downregulated by doxorubicin. We
      demonstrated that silencing of DHODH or inhibition of DHODH activity by brequinar
      dramatically increased the sensitivity of U1690 cells to TRAIL-induced apoptosis
      both in 2D and 3D cultures, and was accompanied by downregulation of c-FLIPL as
      well as by mitochondrial depolarization. In addition, uridine, an end product of
      the pyrimidine synthesis pathway was able to rescue the sensitization effects
      initiated by both brequinar and doxorubicin. Furthermore, several other cancer
      cell lines, LNCaP, MCF-7 and HT-29 were also shown to be sensitized to TRAIL by
      brequinar. Taken together, our findings have identified a novel protein target
      and its inhibitor, brequinar, as a potential agent in TRAIL-based combinatorial
      cancer therapy and highlighted for the first time the importance of mitochondrial
      DHODH enzyme and pyrimidine pathway in mediating TRAIL sensitization in cancer
      cells. 

PMID- 24013226
TI  - MicroRNA-148a suppresses the epithelial-mesenchymal transition and metastasis of
      hepatoma cells by targeting Met/Snail signaling.
AB  - 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). miR-148a is a liver-abundant miRNA. However, the role of miR-148a in
      the development of liver cancer remains largely unknown. In this study, we found
      that, compared with normal livers, miR-148a was significantly decreased in
      hepatocellular carcinoma (HCC) tissues, especially in those with the portal vein
      tumor thrombus. An in vitro transwell assay and an in vivo orthotopic liver
      xenograft model showed that the restoration of miR-148a expression significantly
      repressed the migration and pulmonary metastasis of hepatoma cells. Linear
      regression analysis revealed a positive correlation between the expression of miR
      148a and the mRNA level of E-cadherin gene in human HCC tissues. Both gain- and
      loss-of-function studies disclosed that miR-148a promoted the expression of
      epithelial marker (E-cadherin) and reduced the levels of mesenchymal markers (N
      cadherin, fibronectin or vimentin) in hepatoma cells. These data suggest that miR
      148a may suppress EMT and cancer metastasis. Further mechanistic investigations
      showed that miR-148a directly inhibited Met expression by binding to its 3'-UTR.
      Moreover, the reintroduction of miR-148a attenuated the downstream signaling of
      Met, like activated phosphorylation of AKT-Ser473 and inhibitory phosphorylation
      of GSK-3beta-Ser9, and consequently reduced the nuclear accumulation of Snail, a
      transcription factor that promotes EMT. Taken together, miR-148a may negatively
      regulate Met/Snail signaling and therefore inhibit the EMT and metastasis of
      hepatoma cells. These findings highlight the significance of miR-148a
      downregulation in tumor progression and implicate miR-148a as an attractive
      candidate for cancer therapy. 

PMID- 24013225
TI  - Autocrine HBEGF expression promotes breast cancer intravasation, metastasis and
      macrophage-independent invasion in vivo.
AB  - Increased expression of HBEGF in estrogen receptor-negative breast tumors is
      correlated with enhanced metastasis to distant organ sites and more rapid disease
      recurrence upon removal of the primary tumor. Our previous work has demonstrated
      a paracrine loop between breast cancer cells and macrophages in which the tumor
      cells are capable of stimulating macrophages through the secretion of colony
      stimulating factor-1 while the tumor-associated macrophages (TAMs), in turn, aid
      in tumor cell invasion by secreting epidermal growth factor. To determine how the
      autocrine expression of epidermal growth factor receptor (EGFR) ligands by
      carcinoma cells would affect this paracrine loop mechanism, and in particular
      whether tumor cell invasion depends on spatial ligand gradients generated by
      TAMs, we generated cell lines with increased HBEGF expression. We found that
      autocrine HBEGF expression enhanced in vivo intravasation and metastasis and
      resulted in a novel phenomenon in which macrophages were no longer required for
      in vivo invasion of breast cancer cells. In vitro studies revealed that
      expression of HBEGF enhanced invadopodium formation, thus providing a mechanism
      for cell autonomous invasion. The increased invadopodium formation was directly
      dependent on EGFR signaling, as demonstrated by a rapid decrease in invadopodia
      upon inhibition of autocrine HBEGF/EGFR signaling as well as inhibition of
      signaling downstream of EGFR activation. HBEGF expression also resulted in
      enhanced invadopodium function via upregulation of matrix metalloprotease 2
      (MMP2) and MMP9 expression levels. We conclude that high levels of HBEGF
      expression can short-circuit the tumor cell/macrophage paracrine invasion loop,
      resulting in enhanced tumor invasion that is independent of macrophage signaling.

PMID- 24013227
TI  - Crosstalk-induced loss of miR-126 promotes angiogenesis.
AB  - A molecular environment that promotes vascularization around human carcinomas can
      materialise rapidly, and has been termed the angiogenic switch. Turning this
      switch toward a proangiogenic state involves an altered interplay between tumor
      cells and multiple components of the surrounding stroma. The regulatory landscape
      of these interactions in cervical cancer is now investigated by Huang et al. in
      this issue of Oncogene, who demonstrate that the microRNA miR-126 is
      downregulated during cancer progression, particularly in stromal cells. Such a
      reduction of miR-126 is shown to free at least one target, the proangiogenic
      adrenomedullin, from repression, enhancing vascular growth especially at the in
      situ to invasive carcinoma transition. The study implicates the temporal, spatial
      and progressive nature of tumor-stroma interactions during carcinogenesis, while
      in turn suggesting therapeutic strategies. 

PMID- 24013228
TI  - BMP4/Thrombospondin-1 loop paracrinically inhibits tumor angiogenesis and
      suppresses the growth of solid tumors.
AB  - Bone morphogenetic protein 4 (BMP4) has potential as an anticancer agent. Recent
      studies have suggested that BMP4 inhibits the survival of cancer stem cells
      (CSCs) of neural and colon cancers. Here, we showed that BMP4 paracrinically
      inhibited tumor angiogenesis via the induction of Thrombospondin-1 (TSP1), and
      consequently suppressed tumor growth in vivo. Although HeLa (human cervical
      cancer), HCI-H460-LNM35 (highly metastatic human lung cancer) and B16 (murine
      melanoma) cells did not respond to the BMP4 treatment in vitro, the growth of
      xeno- and allografts of these cells was suppressed via reductions in tumor
      angiogenesis after intraperitoneal treatment with BMP4. When we assessed the mRNA
      expression of major angiogenesis-related factors in grafted tumors, we found that
      the expression of TSP1 was significantly upregulated by BMP4 administration. We
      then confirmed that BMP4 was less effective in suppressing the tumor growth of
      TSP1-knockdown cancer cells. Furthermore, we found that BMP4 reduced vascular
      endothelial growth factor (VEGF) expression in vivo in a TSP1-dependent manner,
      which indicates that BMP4 interfered with the stabilization of tumor
      angiogenesis. In conclusion, the BMP4/TSP1 loop paracrinically suppressed tumor
      angiogenesis in the tumor microenvironment, which subsequently reduced the growth
      of tumors. BMP4 may become an antitumor agent and open a new field of
      antiangiogenic therapy.

PMID- 24013229
TI  - High incidence of female reproductive tract cancers in FA-deficient HPV16
      transgenic mice correlates with E7's induction of DNA damage response, an
      activity mediated by E7's inactivation of pocket proteins.
AB  - Fanconi anemia (FA) is a rare genetic disorder caused by defects in a DNA damage
      repair system, the FA pathway. FA patients frequently develop squamous cell
      carcinoma (SCC) at sites that are associated with human papillomavirus (HPV)
      driven cancer including the female reproductive tract. To assess experimentally
      whether FA deficiency increases susceptibility to HPV-associated cervical/vaginal
      cancer, we monitored cancer incidence in the female lower reproductive tract of
      FA-deficient mice expressing HPV16 oncogenes, E6 and/or E7. FA deficiency
      specifically increased the incidence of cancers in mice expressing E7; but this
      effect was not observed in mice just expressing E6. We also observed that E7, but
      not E6, induced DNA damage as scored by induction of gamma-H2AX and 53BP1 (p53
      binding protein 1) nuclear foci, and this induction was heightened in FA
      deficient tissue. Finally, we discovered that this induction of DNA damage
      responses was recapitulated in mice deficient in expression of 'pocket' proteins,
      pRb, p107 and p130, which are established targets of E7. Our findings support the
      hypothesis that E7 induces cancer by causing DNA damage at least in part through
      the inactivation of pocket proteins. This hypothesis explains why a deficiency in
      DNA damage repair would increase susceptibility to E7-driven cancer. 

PMID- 24013230
TI  - The MutSbeta complex is a modulator of p53-driven tumorigenesis through its
      functions in both DNA double-strand break repair and mismatch repair.
AB  - Loss of the DNA mismatch repair (MMR) protein MSH3 leads to the development of a
      variety of tumors in mice without significantly affecting survival rates,
      suggesting a modulating role for the MutSbeta (MSH2-MSH3) complex in late-onset
      tumorigenesis. To better study the role of MSH3 in tumor progression, we crossed
      Msh3(-/-) mice onto a tumor predisposing p53-deficient background. Survival of
      Msh3/p53 mice was not reduced compared with p53 single mutant mice; however, the
      tumor spectrum changed significantly from lymphoma to sarcoma, indicating MSH3 as
      a potent modulator of p53-driven tumorigenesis. Interestingly, Msh3(-/-) mouse
      embryonic fibroblasts displayed increased chromatid breaks and persistence of
      gammaH2AX foci following ionizing radiation, indicating a defect in DNA double
      strand break repair (DSBR). Msh3/p53 tumors showed increased loss of
      heterozygosity, elevated genome-wide copy-number variation and a moderate
      microsatellite instability phenotype compared with Msh2/p53 tumors, revealing
      that MSH2-MSH3 suppresses tumorigenesis by maintaining chromosomal stability. Our
      results show that the MSH2-MSH3 complex is important for the suppression of late
      onset tumors due to its roles in DNA DSBR as well as in DNA MMR. Further, they
      demonstrate that MSH2-MSH3 suppresses chromosomal instability and modulates the
      tumor spectrum in p53-deficient tumorigenesis and possibly has a role in other
      chromosomally unstable tumors as well.

PMID- 24013231
TI  - Burkitt's lymphoma-associated c-Myc mutations converge on a dramatically altered
      target gene response and implicate Nol5a/Nop56 in oncogenesis.
AB  - Burkitt's lymphomas (BLs) acquire consistent point mutations in a conserved
      domain of Myc, Myc Box I. We report that the enhanced transforming activity of BL
      associated Myc mutants can be uncoupled from loss of phosphorylation and
      increased protein stability. Furthermore, two different BL-associated Myc
      mutations induced similar gene expression profiles independently of T58
      phosphorylation, and these profiles are dramatically different from MycWT.
      Nol5a/Nop56, which is required for ribosomal RNA methylation, was identified as a
      gene hyperactivated by the BL-associated Myc mutants. We show that Nol5a is
      necessary for Myc-induced cell transformation, enhances MycWT-induced cell
      transformation and increases the size of MycWT-induced tumors. Thus, Nol5a
      expands the link between Myc-induced regulation of nucleolar target genes, which
      are rate limiting for cell transformation and tumor growth. 

PMID- 24013233
TI  - Zinc(II) tetraphenyltetrabenzoporphyrin complex as triplet photosensitizer for
      triplet-triplet annihilation upconversion.
AB  - Zn(II) tetraphenyltetrabenzoporphyrin (TPTBP) and the free base H2TPTBP were used
      as triplet photosensitizers for triplet-triplet annihilation (TTA) upconversion,
      to replace the long-established precious metal complex triplet photosensitizers
      such as those containing Pd(II)-Pt(II) atoms.

PMID- 24013232
TI  - Fibulin-3-mediated inhibition of epithelial-to-mesenchymal transition and self
      renewal of ALDH+ lung cancer stem cells through IGF1R signaling.
AB  - Fibulins (FBLNs), a family of extracellular matrix proteins, have recently been
      shown to act as tumor suppressors or activators in different cancers, and the
      underlying molecular mechanisms of their action in cancer remain unclear. We have
      previously shown that the expression of FBLN3 is suppressed by promoter
      hypermethylation and is associated with invasiveness in aggressive non-small cell
      lung cancer. In this study, we evaluated the roles and signaling mechanism of
      FBLN3 in lung cancer stem cells (CSCs). Forced expression of FBLN3 suppressed
      invasion and migration of lung adenocarcinoma cells and decreased the expression
      of epithelial-to-mesenchymal transition (EMT) activators, including N-cadherin
      and Snail. Stemness activities of lung adenocarcinoma cells were also suppressed
      by FBLN3 as indicated by a decrease in spheroid formation and the levels of
      stemness markers such as Sox2 and beta-catenin. These effects of FBLN3 were
      mediated by the glycogen synthase kinase-3beta, GSK3beta/beta-catenin pathway,
      and the upstream regulators of GSK3beta, including phosphoinositide 3-kinase
      (PI3K)/AKT and insulin-like growth factor-1 receptor (IGF1R), were inactivated by
      FBLN3. Moreover, IGF1R was shown to be a direct target of FBLN3, which
      competitively inhibited insulin-like growth factor (IGF) action. To confirm the
      effect of FBLN3 on lung CSCs, aldehyde dehydrogenase-positive (ALDH+) A549 lung
      CSCs were sorted and treated with recombinant FBLN3 protein. FBLN3 clearly
      suppressed EMT, stemness activity and the over-activated IGF1R/PI3K/AKT/GSK3beta
      pathway of the ALDH+ CSC subpopulation. In addition, injection of recombinant
      FBLN3 protein around subcutaneous xenografts established with ALDH+ CSCs in
      athymic nude mice significantly suppressed tumor growth and progression. Overall,
      our results show that FBLN3 suppresses both EMT and self-renewal of the lung CSCs
      by modulating the IGF1R/PI3K/AKT/GSK3beta pathway and that FBLN3 would be useful
      as an alternative CSC therapy.

PMID- 24013234
TI  - Cell cycle perturbations induced by human herpesvirus 6 infection and their
      effect on virus replication.
AB  - In this study, we demonstrate that infection of HSB-2 cells with human
      herpesvirus 6 (HHV-6) resulted in the accumulation of infected cells in the G2/M
      phase of the cell cycle. Analysis of various cell-cycle-regulatory proteins
      indicated that the levels of cyclins A2, B1, and E1 were increased in HHV-6
      infected cells, but there was no difference in cyclin D1 levels between mock
      infected and HHV-6-infected cells. Our data also showed that inducing G2/M phase
      arrest in cells infected by HHV-6 provided favorable conditions for viral
      replication. 

PMID- 24013235
TI  - Molecular and biological properties of tomato necrotic stunt virus and
      development of a sensitive real-time RT-PCR assay.
AB  - The newly identified tomato necrotic stunt virus (ToNStV), with a genome of
      10,057 nucleotides, had 60 % nucleotide sequence and 70 % coat protein amino acid
      sequence identity to other potyviruses. Analysis of a second ToNStV isolate
      revealed two single nucleotide substitutions. ToNStV induced stunting and
      chlorotic to necrotic leaf symptoms on tomato plants. In host-range assays,
      ToNStV systemically infected many species in the family Solanaceae and locally
      infected some species in the families Amaranthaceae, Brassicaceae and
      Cucurbitaceae. A sensitive and reliable real-time RT-PCR assay was developed
      using simply prepared crude tissue extract.

PMID- 24013236
TI  - Rice black-streaked dwarf virus genome segment S5 is a bicistronic mRNA in
      infected plants.
AB  - Rice black-streaked dwarf virus (RBSDV) is a recognized member of the genus
      Fijivirus, family Reoviridae. Genome segment S5 has a putative second ORF
      partially overlapping the major ORF but in a different reading frame. This
      putative ORF is present in a published sequence and in two Chinese isolates now
      sequenced. Antibodies were raised against purified P5-1 and P5-2 fusion proteins
      expressed in a prokaryotic system. In western blots, these antibodies reacted
      with proteins of about 106 and 27 kDa, respectively, as predicted by sequence
      analysis. In immunoelectron microscopy, antibodies to P5-1 reacted with
      viroplasms, indicating that P5-1 is a component of viroplasms, but no labeling
      was observed with P5-2 antisera. Northern blot assays showed that the genome
      segment S5 was transcribed as a single mRNA with no subgenomic RNA. These results
      show that S5 is functionally bicistronic in infected plants. Possible
      translational mechanisms for P5-2 are discussed.

PMID- 24013238
TI  - Current world literature. Adolescent and pediatric gynecology.

PMID- 24013237
TI  - Complete genome sequence analysis of two human enterovirus C99 strains isolated
      in Xinjiang Uighur Autonomous Region, China, in 2011.
AB  - Human enterovirus C99 (EV-C99) is a new member of the species Enterovirus C, and
      although only a few EV-C99 sequences have been obtained thus far, the strain has
      been identified on four continents. In 2011, two EV-C99 strains were isolated
      from two healthy children in Xinjiang, China, and to our knowledge, this is the
      first finding of EV-C99 in China. The two strains, designated HT-XEBGH09F and
      KSSC-ALXHH01F, showed 78.8-86.6 % similarity to other EV-C99 strains and
      exhibited intra-serotypic genetic recombination within the P2 coding regions.
      These findings reflect high genetic divergence among the EV-C99 strains.

PMID- 24013241
TI  - Health reform in the context of entelechy.

PMID- 24013242
TI  - Relationship of personal health experiences with interest in health careers among
      youth from an underserved area.
AB  - Only 10% of health professionals are from racial/ethnic minority groups, and much
      research has been focused on encouraging minorities to enter a health career. The
      lack of health workforce diversity has many implications for the effective
      delivery of care to an increasingly diverse US population. The goal of this
      analysis is to examine the influence of personal health experiences on interest
      in a health career. "Personal Health Experiences" is a newly created scaled
      variable that assesses the influence of direct and indirect health experiences of
      respondents. In a sample of 134 predominantly minority 10th graders from
      underprivileged neighborhoods, the scale had adequate psychometric properties
      (range 1-7; mean 4.44, SD 1.46, median 4.60, Cronbach's alpha 0.72), and
      multivariate regression modeling revealed that it predicted increased "Interest
      in Health Careers" (B=0.46, SE 0.10, p<0.01). Future research is needed to
      determine the role that personal health experiences play in career choices and
      one's success in health career decisions. Such information could, for example,
      help to refine health profession recruitment strategies. 

PMID- 24013243
TI  - Agents of change: undergraduate students' attitudes following observations of
      speech-language pathology service delivery: preliminary findings.
AB  - Undergraduate communication sciences and disorders students' attitudes toward
      speech-language pathology (SLP) clinical services to children and adults prior to
      and following community-based observations were examined. Participants (n=25)
      completed an online survey to elicit their opinions regarding their perceptions
      of their observation experiences. Findings revealed that after completion of
      community-based SLP clinical observations, 16 (64%) respondents reported a
      continued interest in a child-based clinical focus; 12 (48%) respondents
      continued to consider a clinical interest in adults, while 5 respondents (20%)
      changed career interests to an adult focus based on their observation
      experiences. Findings support the notion that observations of SLP appear to
      significantly influence students' career choices. Clinical observations typically
      occur at the junior/senior undergraduate levels; therefore, suggestions are
      offered for inclusion of gerontology education embedded throughout the
      undergraduate communication sciences and disorders curricula to foster and expand
      students' knowledge of aging, and to prepare our students to meet the healthcare
      challenges of elders in the 21st century. 

PMID- 24013244
TI  - Fat phobia of university students: attitudes toward obesity.
AB  - This study examined attitudes about obesity among a sample of university students
      from the departments of Health Sciences and Fine Arts. METHODS: This cross
      sectional study was carried out among first- and second-year students of Health
      Sciences and Fine Arts Yeditepe between April and May 2011. The questionnaire
      surveyed sociodemographic characteristics, height, weight, and a short form of
      the "Fat Phobia" scale. A pilot study revealed that the test-retest reliability
      was r=0.71 and internal consistency (Cronbach alpha) was 0.8783. The mean and SD
      were computed for descriptive purposes, and a t-test was used for hypothesis
      testing; significance was considered for p<0.05. RESULTS: A total of 305 students
      (86 men, 219 women) were included in the study. The mean score on the fat phobia
      scale was 3.57+/-0.69 among the whole group. Fat phobia of women was higher than
      of men (p<0.001). Although the mean score of fat phobia was higher in underweight
      students than in obese students, there was no statistically significant
      differences according to body structure (p>0.05). The adjectives about which the
      whole group was phobic were "likes food" (4.50), "overeats" (4.20), "slow"
      (3.90), "inactive" (3.82), "no will power" (3.71), and "shapeless" (3.66). Female
      students were more phobic than men in adjectives (overeats,) (no will power,)
      (shapeless.) CONCLUSIONS: Fat phobia is common among university students, and
      women are more fat phobic than men. Fat phobia and attitudes toward obesity
      should be examined and followed, and methods and messages directed to change
      negative attitudes should be included during training.

PMID- 24013245
TI  - Clinical education from a specialized accreditation viewpoint: a report of the
      ASAHP clinical education task force.
AB  - Access to clinical education poses national challenges to allied health training
      programs. Clinical education is paramount to providing future health
      professionals with experiences that support competencies for success in their
      individual fields. METHOD: The ASAHP Clinical Education Task Force interviewed 14
      executive directors of various specialized accreditation agencies on clinical
      education issues and opportunities. RESULTS: Interview questions were compiled
      and analyzed by members of the task force. Similarities across disciplines were
      found on the high value of clinical education, key reasons for clinical
      education, and the expansion of interprofessional education. Major differences
      included the use of simulation and its replacement for clinical hours,
      measurement of quality of education and student feedback, and the use of
      portfolio assessment. DISCUSSION: Of 14 professions surveyed, all respondents
      regarded clinical education as "very important" to student competency and
      certification. A common theme was that decisions regarding clinical education
      were under the auspices of the training programs as long as students were able to
      demonstrate specified competencies as per the standards in each field. Most
      directors acknowledged the need to accommodate changes in clinical education
      methodology and some discussed related changes in accreditation requirements.
      CONCLUSION: The 100% participation by executive directors spoke to the
      willingness of the accreditation agencies to share information on education of
      the future healthcare workforce. The clinical education environment is poised for
      innovation in methods to teach skill development and build competencies. ASAHP
      partnership and teamwork with specialized accreditation agencies is a fruitful
      avenue for creating and maintaining excellence in clinical education.

PMID- 24013246
TI  - Practice characteristics and lifestyle choices of men and women physician
      assistants and the relationship to career satisfaction.
AB  - With 60% of practicing physician assistants (PAs) being women, it is critical to
      identify any gender-related differences in career satisfaction. The purpose of
      this study was to identify practice characteristics and lifestyle choices of men
      and women practicing PAs, determine any gender-related differences, and identify
      whether a relationship exists between gender and career satisfaction. This
      descriptive study used a survey addressing career satisfaction, lifestyle
      choices, professional practice characteristics, and gender concerns. Randomly
      selected PAs completed an on-line survey. Nonparametric testing was used to
      analyze the data. Analyses included 85 men and 97 women respondents. More men
      (82.4%) than women (59.8%) were married; a significant association between gender
      and domestic status was found (p=0.009). The way that men rated career
      satisfaction was not significantly different than the way women did (p=0.47).
      Sixty-five percent of men and women completely agreed that they are satisfied
      with their career. Eighty-three percent of men and women PAs believed that they
      can balance their personal and professional responsibilities. While the sample
      was small, it does represent the demographics of PAs currently in practice and
      thus supports the assumption that the PA profession affords the ability to
      balance responsibilities and promotes career satisfaction. 

PMID- 24013247
TI  - Home health physical therapy intervention for an adolescent after intramedullary
      skeletal kinetic distractor limb-lengthening surgery: a case report.
AB  - This case report describes the physical therapy episode of care for an adolescent
      following surgical placement of an intramedullary skeletal kinetic distractor
      (ISKD) to minimize a leg-length discrepancy (LLD). METHODS: A 14-year-old female
      was referred to home health physical therapy 2 weeks after ISKD placement in her
      right femur. The initial evaluation revealed the need to instruct in ISKD limb
      lengthening exercises, strength, flexibility, and endurance exercises and provide
      functional mobility training. RESULTS: The patient received nine treatments over
      8 weeks. Her right femur length increased by 4 cm. Improvements occurred with
      functional mobility, the Bruinincks-Oseretsky Test of Motor Proficiency, and the
      Pediatric Evaluation of Disability Inventory. DISCUSSION: Home health physical
      therapy assisted this patient with reducing her LLD and improving her functional
      mobility. Further research is needed to identify the effectiveness of physical
      therapy interventions on functional mobility for adolescents after ISKD
      placements.

PMID- 24013248
TI  - Measurement error and detectable change for the modified Fresno Test in first
      year entry-level physical therapy students.
AB  - Teaching evidence-based practice (EBP) skills is a core component in the
      education of health care professionals. Methods to assess individual student
      development of these skills are not well studied. The purpose of this study was
      to estimate the standard error of measurement (SEM) and minimal detectable change
      (MDC) for the modified Fresno Test (MFT) of Competence in EBP in first-year
      physical therapy students. Using a test-retest design, the MFT was administered
      two times to 35 participating first-year physical therapy students. Tests were
      scored by two trained physical therapist educators. Mean test scores clustered
      near the middle of the 232 point scoring range, 107 points (SD 14.9) and 103
      points (SD 18.9). Inter-rater reliability [ICC (2, 1)] for scorers was 0.83
      (95%CI 0.74-0.96). Intra-rater reliability was 0.85 (95%CI 0.60-0.97) and 0.94
      (95%CI 0.86-0.99). Test-retest reliability [ICC (2, 1)] was 0.46 (95%CI 0.16
      0.69), with a calculated SEM of 11 points, a confidence in a single measurement
      of 18.2 points, and MDC90 (90% confidence) of 25.7 points. Knowledge about
      estimates of SEM and MDC for specific student populations is important to assess
      change in individual student performance on the modified FT. 

PMID- 24013249
TI  - Discharge planning simulation: training the interprofessional team for the future
      workplace.
AB  - PURPOSE: The integration of interprofessional education (IPE) into health
      professions curricula offers a possible way to increase collaboration among
      health professionals. In this paper we introduce an innovative IPE model of a
      team-based discharge planning case scenario. METHODS: Occupational therapy,
      physician assistant, and physical therapy students (n=173) participated in a
      discharge planning simulation (DPS) focused on a patient with a stroke and
      subsequent hip fracture. A discharge-planning meeting DVD was developed and
      disseminated to the students. Pre and post surveys were sent to the students.
      OUTCOMES: Eighty-nine percent (n=153) of the students responded to the pre-DPS
      survey and 77% (n=132) responded to the post-DPS survey. There was no significant
      difference when comparing pre-DPS or post-DPS by program of study, but
      significant differences were found in three of the four questions when comparing
      individual answers. CONCLUSION: Participation in the DPS model resulted in
      significant changes in perception of a student's individual role as well as the
      role of their interprofessional team members in discharge planning for the
      complex patient. Preliminary results indicate that this model can be a useful
      tool to effectively teach the interprofessional team.

PMID- 24013250
TI  - Gauging patient safety programs.
AB  - In response to evidence that adverse medical events are widespread, patient
      safety programs have emerged and proliferated worldwide in recent years. Patient
      safety may be considered a new and distinct healthcare discipline. It emphasizes
      the reporting, analysis, and prevention of medical errors that can lead to
      adverse healthcare events. While this is a useful generic definition, it takes on
      different meanings for each healthcare discipline. When patient safety programs
      were studied, it was found that many are generic and may be inappropriately
      focused and researched. In planning a patient safety program, the basis of
      patient safety programs for all disciplines will have similarities. But each
      discipline will require nuances specific to the discipline since the goals,
      objectives, and requirements of each are unique. Furthermore, each discipline
      will have its own preferred outcomes that may change over time as new data become
      available and service providers become more knowledgeable of ways to increase the
      likelihood of desired outcomes. 

PMID- 24013251
TI  - Reasons identified for seeking the American Physical Therapy Association
      Credentialed Clinical Instructor Program (CCIP) in Florida.
AB  - The American Physical Therapy Association's (APTA) Strategic Plan strives to
      increase the number of APTA credentialed clinical instructors. Available to all
      health care providers, as of 2012, there were 39,851 credentialed clinical
      instructors. OBJECTIVES: Study purposes were threefold: to determine
      participants' a. reasons to attend the APTA Credentialed Clinical Instructor
      Program (CCIP); b. pre-CCIP learning goals; and c. related post-CCIP learning
      outcomes. METHODS: This IRB-approved study was completed with informed consent
      procedures followed. APTA CCIP credentialed trainers (n=5) developed a survey and
      pilot tested for face and content validity. The instrument included demographics,
      forced choice and open-ended questions. The pre/post survey was administered to
      301 participants of 21 Florida APTA CCIP courses with 5 trainers from 2009-2011.
      Quantitative survey data were collated, tabulated, and summarized comparing
      pre/post data. Narrative data was analyzed for codes and themes, synthesized, re
      contextualized and triangulated by trainers then cross-compared with APTA CCIP
      objectives and trainer expertise. The qualitative insights were presented with
      resulting primary themes and subthemes. RESULTS: Results informed the study
      purposes with a clear determination of the reasons participants attend the APTA
      CCIP, the pre-course goals and post learning outcomes. Participants
      overwhelmingly recommend the APTA CCIP and most receive support from employers
      with geographic course location being a prime reason for course selection.
      Precourse learning goals included 5 over-arching themes, with few sub-themes;
      while post learning outcomes generated 12 specific themes with numerous
      subthemes. CONCLUSIONS: APTA CCIP-credentialed clinical instructors are achieving
      numerous learning outcomes immediately applicable for clinical education.

PMID- 24013252
TI  - Interprofessional education: a pilot study of rehabilitation sciences students
      participating in interdisciplinary international service-learning.
AB  - Various models of interprofessional education, including service-learning, are
      used to teach students how to be effective members of healthcare teams. The
      purpose of this study was to examine pilot data related to the impact of an
      elective one-credit global health course with an international service-learning
      experience (ISL) on the student participants. An interdisciplinary team of 3
      faculty accompanied 4 students representing occupational therapy, physical
      therapy, and speech-language pathology programs for an 8-day ISL experience.
      Students responded to faculty-developed reflection questions pre-travel, during
      travel, and 2-weeks and 4-months post travel. Content analysis was used to
      analyze themes that emerged from the students' written reflections. Three major
      themes emerged: collaboration, satisfaction, and self-discovery. The most
      prominent theme was related to interprofessional collaboration. 

PMID- 24013253
TI  - From buy-in to integration: melding an interprofessional initiative into academic
      programs in the health professions.
AB  - Improvement in the provision of health care is essential in a complex, diverse
      and changing system. Studies are beginning to indicate that interprofessional
      (IP) collaboration can be a means to help address this issue. Institutions that
      have programs in health professions develop Interprofessional Education (IPE)
      programs as a way to introduce and nurture the knowledge, skills, and attitudes
      necessary for IP collaboration. It is expected that health professionals with
      this training will serve patients/clients and communities with safe, effective,
      timely, efficient, equitable and patient/client-centered care that leads to
      decreased medical errors, reduced fragmentation of care, and optimal health
      outcomes. Saint Louis University developed an IPE Program that utilizes a
      sophisticated integrated curriculum featuring courses that intentionally address
      teamwork in patient/client-centered care. There were challenges in integrating
      the IPE curriculum into the University's many diverse programs in the health
      professions. The purpose of this paper is to present the process by which IPE was
      integrated into the curricula of 8 different health professional programs.
      Benefits, opportunities, challenges and strategies of this process are presented
      and discussed. It is expected that this change in culture will produce improved
      patient/client outcomes. 

PMID- 24013254
TI  - "I was able to have a voice without being self-conscious": students' perceptions
      of audience response systems in the health sciences curriculum.
AB  - Audience Response Systems (ARS or "clickers") are becoming a popular addition to
      the college classroom. Instructors are using this educational technology to
      elicit feedback from students, to determine students' knowledge of content before
      or during lectures, and to increase participation in the classroom. The purpose
      of this study was to examine first-year allied health students' perceptions of
      the impact of clickers on participation during an introductory health professions
      course. METHOD: At the mid-point of the course, students completed a survey that
      assessed their perception of classroom participation. During the second half of
      the course, clickers were introduced to classroom activities. The survey was re
      administered at the end of the course; students also had the opportunity to write
      a narrative comment. RESULTS: Students felt that clickers increased their level
      of interaction with the instructor and participation of the class as a whole.
      CONCLUSION: Clickers may be a practical way to increase student participation in
      first-year allied health courses.

PMID- 24013256
TI  - A novel approach for rescuing and scleral fixating a posterior dislocated
      intraocular lens/bag complex without conjunctival opening.

PMID- 24013255
TI  - Ovomucoid is not superior to egg white testing in predicting tolerance to baked
      egg.
AB  - BACKGROUND: Children with egg allergy may tolerate baked egg products. Ovomucoid
      specific IgE (sIgE) antibody levels have been suggested to predict outcomes of
      baked egg challenges. OBJECTIVE: We determined the relationship of ovomucoid and
      egg white sIgE levels and egg white skin prick test (SPT) wheal size with baked
      egg challenge outcome. METHODS: Retrospective review of 1186 patients who
      underwent ovomucoid sIgE blood testing. Subset analysis was of 169 patients who
      underwent baked egg food challenges. RESULTS: Egg white sIgE, ovomucoid sIgE, and
      egg white SPT were different among those eating regular egg, eating baked egg
      only, or avoiding all egg (P < .001 for all). One hundred forty-two of 169
      patients (84.0%) passed baked egg challenges. We were able to establish >90%
      predictive values for passing baked egg challenge for egg white sIgE, ovomucoid
      sIgE, and egg white SPT.No patient with egg white SPT wheal <3 mm failed a baked
      egg challenge. Receiver operating characteristic curve analysis of egg white
      sIgE, ovomucoid sIgE, and egg white SPT showed areas under the curve of 0.721,
      0.645, and 0.624, respectively. No significant difference was observed among
      these immunologic parameters in their abilities to predict baked egg challenge
      outcome (P [ .301). CONCLUSION: Most children with egg allergy in this study
      passed baked egg challenges. Ovomucoid sIgE, although a useful clinical predictor
      of baked egg tolerance, was not superior to egg white SPT or sIgE in predicting
      outcome of baked egg challenge.

PMID- 24013257
TI  - Fluid dynamics of vitrectomy probes.
AB  - PURPOSE: To characterize the fluidics of vitreous cutter port in response to
      aspiration and blade motion using particle image velocimetry techniques. Diverse
      surgical scenarios and fluid characteristics were replicated. METHODS: The 23
      gauge vitreous cutters were immersed in seeded Balanced Salt Solution (BSS)
      (Alcon, Forth Worth, TX) or egg albumen, and high-speed video was recorded. Fluid
      velocity, kinetic energy (KE), and acceleration generated by Venturi and
      peristaltic pumps were measured in aspiration only (200 and 300 mmHg), low-speed
      vitrectomy (1,600 cuts per minute; 200 mmHg vacuum), and high-speed vitrectomy
      (3,000 cuts per minute; 300 mmHg vacuum) modes. RESULTS: The Venturi pump
      generated significantly higher KE than peristaltic pump in BSS (P < 0.0001 for
      each pair), and aspiration only yielded significantly higher KE. Cutting
      activation generated significant acceleration (P < 0.001), and the peristaltic
      pump produced higher positive and negative acceleration peaks (P < 0.001) than
      the Venturi pump. In egg albumen, the peristaltic pump generated significantly
      more KE than the Venturi pump (P < 0.001) and perturbed a much wider area.
      Acceleration was higher for the peristaltic pump in low-speed mode (P < 0.001),
      whereas in high-speed modality, the Venturi pump produced the highest
      acceleration peaks (P < 0.001). CONCLUSION: Pump type and blade motion largely
      influence velocity, KE, and acceleration. In BSS, the Venturi pump induces higher
      KE and acceleration, although perturbing fluid less diffusely. In egg albumen,
      the peristaltic pump perturbed a much wider area and induced a higher KE and
      acceleration than the Venturi pump, even more so at lower cut rates. As a
      conclusion, particle image velocimetry allowed precise characterization of fluid
      velocity in response to cutter activation, suggesting a pragmatic approach to
      surgical scenarios.

PMID- 24013258
TI  - Acute retinal pigment epithelium detachments after photocoagulation.
AB  - PURPOSE: To characterize the morphology of patterned scanning laser (PASCAL)
      panretinal photocoagulation. METHODS: In this prospective cohort study, patients
      with proliferative diabetic retinopathy or severe nonproliferative diabetic
      retinopathy with high-risk characteristics, who were treated with PASCAL
      panretinal photocoagulation as part of their indicated clinical course, were
      serially imaged with spectral domain optical coherence tomography. Thirty eyes of
      25 patients were studied from 1 hour to 21 weeks after laser treatment. RESULTS:
      Over a quarter (26.1%) of all treatment spots were imaged by spectral domain
      optical coherence tomography 1 hour after PASCAL panretinal photocoagulation. At
      1 hour (+/-30 minutes) after PASCAL treatment, spectral domain optical coherence
      tomography demonstrated retinal pigment epithelium detachment in 23 of 27 eyes
      (85.2%) and in 36.1% of all imaged laser spots. Detachments occurred
      preferentially at the photocoagulation edges in 48.4% of pigment epithelium
      detachments (PEDs). Linear regression analysis revealed that average laser power
      (Pearson's r = 0.671, P < 0.001) and average laser energy (Pearson's r = 0.588, P
      = 0.001) were significantly associated with PEDs observed 1 hour after treatment.
      Pigment epithelium detachments occurred at a rate of 9.2% +/- 4.9% at an average
      power of 0 mW to 400 mW, 37.8% +/- 9.5% at 401 mW to 800 mW, 42.1% +/- 5.6% at
      801 mW to 1,200 mW, and 53.6% +/- 5.7% at >1,200 mW. By a 1-week follow-up, no
      PEDs were observed, and the retinal pigment epithelium appeared morphologically
      similar to its preoperative structure by 3 weeks. Patient characteristics (study
      eye, sex, race, diagnosis, age, preoperative blood glucose, hemoglobin A1C,
      duration of diabetes, and body mass index) and other PASCAL parameters (number of
      laser applications, spot size, pulse duration, and average laser fluence) were
      not significantly associated with PEDs. CONCLUSION: Retinal pigment epithelium
      detachment occurs 1 hour after PASCAL treatment over a wide range of laser
      settings. Laser power and energy are positively correlated with the occurrence of
      PEDs, which are no longer observed by 1-week follow-up. Future studies might
      examine various acute posttreatment time points and directly compare the
      morphology of PASCAL burns with that of longer pulse-duration laser modalities.

PMID- 24013259
TI  - Choroidal thickness measurement in children using optical coherence tomography.
AB  - PURPOSE: To measure choroidal thickness (CT) in children of various ages by using
      spectral optical coherence tomography with enhanced depth imaging and to
      investigate the association between subfoveal CT and ocular axial length, age,
      gender, weight, and height in children. METHODS: Healthy children were
      prospectively included between May and August 2012. Optical coherence tomography
      with the enhanced depth imaging system (Spectralis, Heidelberg, Germany) was used
      for choroidal imaging at nine defined points of the macula of both eyes. Axial
      length was measured using IOLMaster (Carl Zeiss Meditec, Dublin, CA). Height,
      weight, and refraction were recorded. Interobserver agreement in readings was
      also assessed by the Bland-Altman Method. RESULTS: Three hundred and forty-eight
      eyes from 174 children aged 3.5 years to 14.9 years were imaged. The mean
      subfoveal CT in right eyes was 341.96 +/- 74.7 um. Choroidal thickness increased
      with age (r = 0.24, P = 0.017), height, and weight but not with gender (P >
      0.05). It was also inversely correlated to the axial length (r = 0.24, P =
      0.001). The nasal choroid appeared thinner than in the temporal area (analysis of
      variance, P < 0.0001). CONCLUSION: In children, CT increases with age and is
      inversely correlated to axial length. There is a significant variation of CT
      between children of the same age.

PMID- 24013260
TI  - Effect of 360 degrees  episcleral band as adjunctive to pars plana vitrectomy and
      silicone oil tamponade in the management of myopic macular hole retinal
      detachment.
AB  - PURPOSE: To report the effect of 360 degrees  scleral band in combination with
      pars plana vitrectomy (PPV) and silicone oil tamponade on the anatomical success
      and on the closure of macular hole (MH) in cases of myopic macular hole retinal
      detachment. METHODS: A retrospective consecutive interventional study from
      medical records on patients who had pars plana vitrectomy and silicone oil. with
      or without 360 degrees  scleral band for the treatment of retinal detachment
      associated with MH. The cases were operated in the period from February 2006 to
      May 2012. The included cases were classified into two groups: the first group
      with scleral band and the second group without scleral band. The primary
      anatomical success and optical coherence tomography patterns of MH closure were
      the main outcomes. RESULTS: After the first procedure, the overall success rate
      was 90.6% (in both groups). In 9.4%, there was recurrent retinal detachment. In
      the first group the success rate was 89.5%, and in 10.5% there was recurrent
      retinal detachment. In the second group 92.5% was success and 7.5% was recurrent
      retinal detachment. After the second interference, the success rate was 98.4% in
      both groups. Closure of MH was achieved in 45.2% in both groups. In the first
      group, there was closure of MH in 43.5%, while in 47.8% the hole remained open
      flat, in 4.3% the hole closed partially and in 4.3% there was macular scar. In
      the second group, MH closure was achieved in 47.4%, whereas in 52.6% the hole was
      open flat. CONCLUSION: The use of 360 degrees  band in combination with pars
      plana vitrectomy and silicone oil offered no additional effect on either the
      anatomical success or the rate of MH closure in the management of myopic macular
      hole retinal detachment. Four patterns of MH were reported closed MH, partial
      thickness MH, open flat MH, and macular scar.

PMID- 24013261
TI  - Pars plana vitrectomy for vitreomacular traction syndrome: a systematic review
      and metaanalysis of safety and efficacy.
AB  - PURPOSE: To determine the safety and efficacy of pars plana vitrectomy for
      vitreomacular traction. METHODS: Articles reporting visual acuity change before
      and after pars plana vitrectomy were selected using a systematic literature
      review with predefined eligibility criteria. Visual acuities were converted to
      logarithm of the minimum angle of resolution (logMAR), weighted for study size,
      and pooled across studies. Safety outcomes were also pooled across studies.
      RESULTS: Twenty-one of 460 articles were eligible. Mean (+/-standard deviation)
      logMAR visual acuity improved from 0.67 +/- 0.55 to 0.42 +/- 0.45 (n = 259 eyes)
      after pars plana vitrectomy (from 20/94 to 20/53 Snellen). In series of at least
      20 eyes, mean visual acuity improved in all 5 studies (sign test, P = 0.0625). Of
      392 eyes, 9.2% lost visual acuity, 11.7% were unchanged, and 64.3% improved;
      32.9% of 217 eyes gained >=2 Snellen lines. The most common postoperative
      complications were cataract (34.7% of 304 eyes; 63.2% of 68 phakic eyes),
      epiretinal membrane (5.7% of 348 eyes), and retinal detachment (4.6% of 348
      eyes). Cataract surgery was undertaken in 10.5% of eyes. CONCLUSION: The visual
      acuity gains after pars plana vitrectomy for vitreomacular traction are
      relatively modest, but visual acuity change may not fully reflect symptomatic
      relief.

PMID- 24013262
TI  - Myopic stretch lines: linear lesions in fundus of eyes with pathologic myopia
      that differ from lacquer cracks.
AB  - PURPOSE: To clarify the pathophysiology of linear hypofluorescent lesions
      observed by fluorescein angiography (FA) in the posterior fundus of eyes with
      pathologic myopia and to compare the features of these lesions with those of
      lacquer cracks. METHODS: Medical records of 117 eyes of 81 highly myopic
      patients, which had linear lesions with abnormal fluorescence by FA were
      reviewed. Features obtained by fundus autofluorescence, indocyanine green
      angiography, and optical coherence tomography were also analyzed. RESULTS: In 37
      of 117 eyes, the linear lesions were hyperfluorescent in the fluorescein
      angiograms and appeared yellowish ophthalmoscopically. Optical coherence
      tomography showed discontinuities of retinal pigment epithelium; thus, they were
      considered to represent lacquer cracks. In the remaining 80 eyes, the linear
      lesions were hypofluorescent by FA and ophthalmoscopic observation showed
      pigmented brown lines. Optical coherence tomography showed clumps of retinal
      pigment epithelium at the corresponding sites. Although indocyanine green
      angiography showed hypofluorescence in both types of lesions, fundus
      autofluorescence showed hyperautofluorescence of hypofluorescent lines by FA and
      hypoautofluorescence of lacquer cracks. Hypofluorescent lines by FA were
      considered to be the same as myopic stretch lines. CONCLUSION: There are two
      types of linear lesions in the posterior fundus of highly myopic eyes; lacquer
      cracks and myopic stretch lines, and they should be differentiated.

PMID- 24013263
TI  - Both PAX4 and MAFA are expressed in a substantial proportion of normal human
      pancreatic alpha cells and deregulated in patients with type 2 diabetes.
AB  - Pax4 and MafA (v-maf musculoaponeurotic fibrosarcoma oncogene homolog A) are two
      transcription factors crucial for normal functions of islet beta cells in the
      mouse. Intriguingly, recent studies indicate the existence of notable difference
      between human and rodent islet in terms of gene expression and functions. To
      better understand the biological role of human PAX4 and MAFA, we investigated
      their expression in normal and diseased human islets, using validated antibodies.
      PAX4 was detected in 43.0+/-5.0% and 39.1+/-4.0% of normal human alpha and beta
      cells respectively. We found that MAFA, detected in 88.3+/-6.3% insulin(+)cells
      as in the mouse, turned out to be also expressed in 61.2+/-6.4% of human
      glucagons(+) cells with less intensity than in insulin(+) cells, whereas MAFB
      expression was found not only in the majority of glucagon(+) cells (67.2+/-7.6%),
      but also in 53.6+/-10.5% of human insulin(+) cells. Interestingly, MAFA nuclear
      expression in both alpha and beta cells, and the percentage of alpha cells
      expressing PAX4 were found altered in a substantial proportion of patients with
      type 2 diabetes. Both MAFA and PAX4 display, therefore, a distinct expression
      pattern in human islet cells, suggesting more potential plasticity of human
      islets as compared with rodent islets. 

PMID- 24013264
TI  - Currarino syndrome: report of five consecutive patients.
AB  - INTRODUCTION: The Currarino syndrome is regarded as a developmental disorder
      based on its recognized etiological heterogeneity. This syndrome is thought to
      result from abnormal separation of the neuroectoderm from the endoderm. Our aim
      was to report the neurosurgical management of Currarino syndrome in children and
      adults and to describe what clinician could do if the Currarino triad was
      suspected. CASE REPORTS: We present five cases of Currarino triad who underwent
      surgical intervention. All patients had sacral bony deformity, anorectal
      malformations, and anterior sacral meningocele. A 40-year-old-male had chronic
      constipation. He was incidentally diagnosed with Currarino syndrome. A 19-year
      old-female suffered from a slight weakness in lower extremities and urinary
      incontinence. Her past medical history was remarkable for anal atresia. The other
      three cases were children. CONCLUSION: When an anterior sacral meningocele is
      encountered, Currarino syndrome should be taken into consideration. Although it
      is rarity, the Currarino syndrome might be one of the causes of chronic
      constipation. Endoscopic or endoscope-assisted surgery via a posterior sacral
      route can be feasible for treatment of some of the patients with anterior sacral
      meningocele. Anterior meningocele pouch associated with Currarino syndrome will
      regresses over time following transdural ligation of its neck.

PMID- 24013265
TI  - Clinical features and endovascular treatment of intracranial arteriovenous
      malformations in pediatric patients.
AB  - PURPOSE: The purpose of this study was to characterize clinical features and
      evaluate the clinical outcome of endovascular embolization treatment intracranial
      arteriovenous malformations in pediatric patients. METHODS: A cohort of children
      (age <= 18 years) with arteriovenous malformations (AVMs) from 2000 to 2012 was
      included. Predictors studied included patient gender, age, and angioarchitectural
      features, including AVM location, nidus morphology and size, venous drainage, and
      associated aneurysms. Treatment method, complications and outcomes were recorded.
      The features of AVMs were evaluated before the treatment. RESULTS: One hundred
      twenty-seven children (77 males, mean age 13.2 years) were included; 90/127 (70.9
      %) children were presented with hemorrhage. AVM size and deep venous drainage
      were independently associated with hemorrhage; 66/127 patients (52 %) treated
      with endovascular embolization. Complete obliteration at the end of all
      endovascular procedures was achieved in 14/66 patients (21.2 %), with an average
      of 78 % (range, 20-100 %) volume reduction. A mean of 2.9 (range, 1-9) feeding
      pedicles was embolized per patient. Overall, nine complications occurred in a
      total of 123 procedures (7.3 %). There was no procedure-related death in this
      study population. There was no significant difference between patients with and
      without complications in terms of AVM grade, demographic characteristics, or
      embolization features. CONCLUSIONS: AVM size and deep venous drainage were
      independently associated with hemorrhage in pediatric patients. Endovascular
      procedure is feasible and safe for pediatric AVMs, and complete embolization can
      be achieved in small AVMs, while large AVMs can be adequately reduced in size for
      additional microsurgery or stereotactic radiosurgery.

PMID- 24013266
TI  - Mast cells in the human dura: effects of age and dural bleeding--authors' reply.

PMID- 24013267
TI  - Association between body water status and acute mountain sickness.
AB  - PURPOSE: The present study determined the association between body fluid
      variation and the development of acute mountain sickness (AMS) in adults.
      METHODS: Forty-three healthy participants (26 males and 17 females, age: 26 +/- 6
      yr, height: 174 +/- 9 cm, weight: 68 +/- 12 kg) were passively exposed at a FiO2
      of 12.6% (simulated altitude hypoxia of 4500 m, PiO2 = 83.9 mmHg) for 12-h. AMS
      severity was assessed using the Lake Louise Score (LLS). Food and drink intakes
      were consumed ad libitum and measured; all urine was collected. Before and after
      the 12-h exposure, body weight and plasma osmolality were measured and whole-body
      bioimpedance analysis was performed. RESULTS: The overall AMS incidence was 43%
      (38% males, 50% females). Participants who developed AMS showed lower fluid
      losses (3.0 +/- 0.9 vs. 4.5 +/- 2.0 ml/kg/h, p = 0.002), a higher fluid retention
      (1.9 +/- 1.5 vs. 0.6 +/- 0.8 ml/kg/h, p = 0.022), greater plasma osmolality
      decreases (-7 +/- 7 vs. -2 +/- 5 mOsm/kg, p = 0.028) and a larger plasma volume
      expansion (11 +/- 10 vs. 1 +/- 15%, p = 0.041) compared to participants not
      developing AMS. Net water balance (fluid intake--fluid loss) and the amount of
      fluid loss were strong predictors whether getting sick or not (Nagelkerkes r(2) =
      0.532). The LLS score was related to net water balance (r = 0.358, p = 0.018),
      changes in plasma osmolality (r = -0.325, p = 0.033) and sodium concentration (r
      = -0.305, p = 0.047). Changes in the impedance vector length were related to
      weight changes (r = -0.550, p<0.001), fluid intake (r = -0.533, p<0.001) and net
      water balance (r = -0.590, p<0.001). CONCLUSIONS: Participants developing AMS
      within 12 hours showed a positive net water balance due to low fluid loss. Thus
      measures to avoid excess fluid retention are likely to reduce AMS symptoms.

PMID- 24013269
TI  - The effects of a group-based cognitive behavioral therapy on people with multiple
      sclerosis: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the effectiveness of a cognitive behavioral group-based
      intervention aimed at reducing depression and fostering quality of life and
      psychological well-being of multiple sclerosis patients through the promotion of
      identity redefinition, sense of coherence, and self-efficacy. DESIGN: A
      randomized controlled trial. SETTING: Non-medical setting, external to the
      Multiple Sclerosis Clinic Centre. SUBJECTS: Eighty-two patients: 64% women; mean
      age 40.5, SD = 9.4; 95% with relapsing-remitting multiple sclerosis; Expanded
      Disability Status Scale (EDSS) between 1 and 5.5 were included in the study.
      INTERVENTIONS: Patients were randomly assigned to an intervention group (five
      cognitive behavioral group-based sessions, n = 41) or to a control group (three
      informative sessions, n = 41). MAIN MEASURES: Depression (CES-D), Quality of life
      (MSQOL revised), Psychological well-being (PANAS), Identity Motives Scale, Sense
      of Coherence (SOC), and Self Efficacy in Multiple Sclerosis. RESULTS: Quality of
      life increased in the intervention group compared with the control at 6-months
      follow-up (mean change 0.72 vs. -1.76, p < 0.05). Well-being in the intervention
      group increased for males and slightly decreased for females at 6-months follow
      up (mean change 6.58 vs. -0.82, p < 0.05). Contrasts revealed an increase in self
      efficacy in the intervention group at posttreatment compared with the control
      (mean change 2.95 vs. -0.11, p < 0.05). Depression tended to lower, while
      identity and coherence increased in the intervention group compared with the
      control, though the differences were not significant. CONCLUSIONS: Preliminary
      evidence suggests that intervention promotes patients' quality of life and has an
      effect on psychological well-being and self-efficacy.

PMID- 24013268
TI  - A dual-task home-based rehabilitation programme for improving balance control in
      patients with acquired brain injury: a single-blind, randomized controlled pilot
      study.
AB  - OBJECTIVE: To evaluate the safety, feasibility and effectiveness of a dual-task
      home-based rehabilitation programme on balance impairments among adult patients
      with acquired brain injury. DESIGN: Single-blind, randomized controlled pilot
      study. SETTING: Single rehabilitation centre. SUBJECTS: Sixteen participants
      between 12 and 18 months post-acquired brain injury with balance impairments and
      a score <10 seconds on the One-Leg Stance Test (eyes open). INTERVENTION: All
      participants received 50-minutes individualised traditional physiotherapy
      sessions three times a week for seven weeks. In addition, the intervention group
      (N = 8) performed an individualised dual-task home-based programme six days a
      week for seven weeks. MAIN OUTCOME MEASURES: The primary outcome measure was the
      Balance Evaluation System Test; secondary measures were the Activities-specific
      Balance Confidence Scale and Goal Attainment Scaling. RESULTS: At the end of the
      pilot study, the intervention group showed significantly greater improvement in
      Balance Evaluation System Test scores (17.87, SD 6.05) vs. the control group
      (5.5, SD 3.53; P = 0.008, r = 0.63). There was no significant difference in
      improvement in Activities-specific Balance Confidence Scale scores between the
      intervention group (25.25, SD 25.51) and the control group (7.00, SD 14.73; P =
      0.11, r = 0.63). There was no significant improvement in Goal Attainment Scaling
      scores in the intervention (19.37, SD 9.03) vs. the control group (16.28, SD
      6.58; P = 0.093, r = 0.63). CONCLUSIONS: This pilot study shows the safety,
      feasibility and short-term benefit of a dual-task home-based rehabilitation
      programme to improve balance control in patients with acquired brain injury. A
      sample size of 26 participants is required for a definitive study.

PMID- 24013270
TI  - Physical activity maintenance in patients with rheumatoid arthritis: a
      qualitative study.
AB  - OBJECTIVE: To describe the experience of physical activity maintenance in
      patients with rheumatoid arthritis. DESIGN: A qualitative salutogenic-oriented
      interview study. SETTING: A rheumatology outpatient clinic. SUBJECTS: A purposive
      sample of 16 physically active patients (mean age 50, range 37-67) diagnosed with
      rheumatoid arthritis on average 21 years previously (range 4-46 years). METHODS:
      In-depth interviews were conducted using a semi-structured interview guide to
      illuminate how the phenomenon 'physical activity maintenance' was experienced by
      patients with rheumatoid arthritis. The interviews were analysed using systematic
      text condensation, inspired by Giorgi's descriptive phenomenological methodology.
      RESULTS: The analysis revealed three categories: (1) knowing and enjoying the
      body; (2) responsibility and challenges; (3) autonomy and social belonging. On
      the basis of these categories, the essential meaning of the phenomenon of
      physical activity maintenance for patients with rheumatoid arthritis was
      summarized into 'striving for a transparent body and participation', pointing to
      experiences of sensations of wellbeing, liberation from restrictions and social
      participation on equal terms with non-arthritis populations. CONCLUSION: This
      study demonstrates that physical activity in patients with rheumatoid arthritis
      may be understood as a resource to resist disability and to feel and stay healthy
      while creating and sustaining meaningfulness in life.

PMID- 24013272
TI  - High-pressure carbon dioxide uptake for porous organic cages: comparison of
      spectroscopic and manometric measurement techniques.
AB  - A chemoselective spectroscopic method for measuring CO2 sorption isotherms at
      pressures up to 14 MPa (140 bar) is validated against manometric measurements and
      molecular simulations, giving insights into the preferred sorption sites in
      various crystalline porous organic cages. 

PMID- 24013271
TI  - Genipin inhibits TNF-alpha-induced vascular smooth muscle cell proliferation and
      migration via induction of HO-1.
AB  - Vascular smooth muscle cell (VSMC) proliferation and migration triggered by
      inflammatory stimuli contributes importantly to the pathogenesis of
      atherosclerosis and restenosis. On the other hand, genipin, an aglycon of
      geniposide, exhibits diverse pharmacological functions such as antitumor and anti
      inflammatory effects. The protective effects of genipin on the cardiovascular
      system have also been reported. However, the molecular mechanism involved remains
      unknown. This study aimed to elucidate the precise function of genipin in VSMCs,
      focusing particularly on the role of heme oxygenase-1 (HO-1), a potent anti
      inflammatory enzyme. We found that pretreatment of genipin induced HO-1 mRNA and
      protein levels, as well as its activity in VSMCs. Genipin inhibited TNF-alpha
      induced VSMC proliferation and migration in a dose-dependent manner. At the
      molecular level, genipin prevented ERK/MAPK and Akt phosphorylation while left
      p38 MAPK and JNK unchanged. Genipin also blocked the increase of ROS generation
      induced by TNF-alpha. More importantly, the specific HO-1 siRNA partially
      abolished the beneficial effects of genipin on VSMCs. These results suggest that
      genipin may serve as a novel drug in the treatment of these pathologies by
      inducing HO-1 expression/activity and subsequently decreasing VSMC proliferation
      and migration. 

PMID- 24013273
TI  - Intron 3 of the ARID5B gene: a hot spot for acute lymphoblastic leukemia
      susceptibility.
AB  - PURPOSE: Single-nucleotide polymorphisms (SNPs) in AT-rich interactive domain 5B
      (ARID5B) have been associated with risk for pediatric acute lymphoblastic
      leukemia (ALL). After reviewing previous studies, we realized that the most
      significant associations were restricted to intron 3, but the mechanism(s) by
      which those SNPs affect ALL risk remain to be elucidated. Therefore, the aim of
      this study was to analyze the association between genetic variants of the intron
      3 region of ARID5B and the incidence of B-ALL in a Spanish population. We also
      aimed to find a functional explanation for the association, searching for copy
      number variations (CNVs), and changes in ARID5B expression associated with the
      genotypes of the SNPs. METHODS: We analyzed 10 SNPs in intron 3 of ARID5B in a
      Spanish population of 219 B-ALL patients and 397 unrelated controls with the
      Taqman Open Array platform. CNVs were analyzed in 23 patients and 17 controls
      using the Cytogenetics Whole-genome 2.7 M platform. Expression of ARID5B
      transcript 1 was quantified by qPCR and related to SNPs genotype in seven ALL
      cell lines. RESULTS: Association between intron 3 and B-ALL risk was confirmed
      for all of the SNPs evaluated in our Spanish population. We could not explain
      this association by the presence of CNVs. We neither detected changes in the
      expression of ARID5B isoform associated with the genotype of the SNPs.
      CONCLUSIONS: The intron 3 of ARID5B gene was found to be strongly associated with
      B-ALL risk in the Spanish population examined. However, neither CNVs nor changes
      in mRNA expression were found to be responsible for this association.

PMID- 24013274
TI  - Fifty years of progressive supranuclear palsy.

PMID- 24013275
TI  - Measuring decline in prodromal AD: a pike to hike.

PMID- 24013276
TI  - Science in pictures: Visual representation of climate change in Spain's
      television news.
AB  - The images used by the media to represent science can help people's understanding
      of complex processes and create meaningful links with audiences. This is
      particularly relevant in the case of climate change (CC), an important phenomenon
      that, nevertheless, is often perceived as a remote issue, with no relevance to
      daily life. This article presents the main results of a research on the images
      used in television news to represent CC. From a sample of 1476.4 hours of Spanish
      television news programmes, a content analysis of 78 stories on climate change
      was carried out. This was complemented with six semi-structured interviews at
      five TV newsrooms. Results indicate that the low rate of coverage of CC can be
      related to the scarcity of attractive images available to the channels.

PMID- 24013277
TI  - Receiver psychology turns 20: is it time for a broader approach?
AB  - Twenty years ago, a new conceptual paradigm known as 'receiver psychology' was
      introduced to explain the evolution of animal communication systems. This
      paradigm advanced the idea that psychological processes in the receiver's nervous
      system influence a signal's detectability, discriminability and memorability, and
      thereby serve as powerful sources of selection shaping signal design. While
      advancing our understanding of signal diversity, more recent studies make clear
      that receiver psychology, as a paradigm, has been structured too narrowly and
      does not incorporate many of the perceptual and cognitive processes of signal
      reception that operate between sensory transduction and a receiver's response.
      Consequently, the past two decades of research on receiver psychology have
      emphasized considerations of signal evolution but failed to ask key questions
      about the mechanisms of signal reception and their evolution. The primary aim of
      this essay is to advocate for a broader receiver psychology paradigm that more
      explicitly includes a research focus on receivers' psychological landscapes. We
      review recent experimental studies of hearing and sound communication to
      illustrate how considerations of several general perceptual and cognitive
      processes will facilitate future research on animal signalling systems. We also
      emphasize how a rigorous comparative approach to receiver psychology is critical
      to explicating the full range of perceptual and cognitive processes involved in
      receiving and responding to signals.

PMID- 24013278
TI  - A distinct mechanism for activating uncoupled nicotinic acetylcholine receptors.
AB  - The ability of the nicotinic acetylcholine receptor (nAChR) to undergo
      conformational transitions is exquisitely sensitive to its surrounding lipid
      environment. Previous work has highlighted a conformational selection mechanism,
      whereby different lipids stabilize different proportions of activatable resting
      versus nonactivatable conformations. In the absence of anionic lipids and
      cholesterol, the nAChR adopts an uncoupled conformation, which binds agonist with
      resting state-like affinity but does not usually undergo agonist-induced
      conformational transitions. Very slow (minutes to hours) transitions from
      uncoupled to coupled (resting, open and/or desensitized) conformations, however,
      can occur in membranes with relatively thick hydrophobic cores. Increasing
      membrane hydrophobic thickness 'awakens' uncoupled nAChRs by reducing the large
      activation energy barrier (or barriers) leading to coupled states, thus allowing
      conformational transitions to occur on an experimentally tractable timescale.
      Lipids shape activity by modulating the relative proportions of activatable
      versus nonactivatable conformations and by controlling the transitions between
      uncoupled and coupled conformations. 

PMID- 24013279
TI  - Metrics other than potency reveal systematic variation in responses to cancer
      drugs.
AB  - Large-scale analysis of cellular response to anticancer drugs typically focuses
      on variation in potency (half-maximum inhibitory concentration, (IC50)), assuming
      that it is the most important difference between effective and ineffective drugs
      or sensitive and resistant cells. We took a multiparametric approach involving
      analysis of the slope of the dose-response curve, the area under the curve and
      the maximum effect (Emax). We found that some of these parameters vary
      systematically with cell line and others with drug class. For cell-cycle
      inhibitors, Emax often but not always correlated with cell proliferation rate.
      For drugs targeting the Akt/PI3K/mTOR pathway, dose-response curves were
      unusually shallow. Classical pharmacology has no ready explanation for this
      phenomenon, but single-cell analysis showed that it correlated with significant
      and heritable cell-to-cell variability in the extent of target inhibition. We
      conclude that parameters other than potency should be considered in the
      comparative analysis of drug response, particularly at clinically relevant
      concentrations near and above the IC50. 

PMID- 24013280
TI  - Putrescine overproduction does not affect the catabolism of spermidine and
      spermine in poplar and Arabidopsis.
AB  - The effect of up-regulation of putrescine (Put) production by genetic
      manipulation on the turnover of spermidine (Spd) and spermine (Spm) was
      investigated in transgenic cells of poplar (Populus nigra * maximowiczii) and
      seedlings of Arabidopsis thaliana. Several-fold increase in Put production was
      achieved by expressing a mouse ornithine decarboxylase cDNA either under the
      control of a constitutive (in poplar) or an inducible (in Arabidopsis) promoter.
      The transgenic poplar cells produced and accumulated 8-10 times higher amounts of
      Put than the non-transgenic cells, whereas the Arabidopsis seedlings accumulated
      up to 40-fold higher amounts of Put; however, in neither case the cellular Spd or
      Spm increased consistently. The rate of Spd and Spm catabolism and the half-life
      of cellular Spd and Spm were measured by pulse-chase experiments using [(14)C]Spd
      or [(14)C]Spm. Spermidine half-life was calculated to be about 22-32 h in poplar
      and 52-56 h in Arabidopsis. The half-life of cellular Spm was calculated to be
      approximately 24 h in Arabidopsis and 36-48 h in poplar. Both species were able
      to convert Spd to Spm and Put, and Spm to Spd and Put. The rates of Spd and Spm
      catabolism in both species were several-fold slower than those of Put, and the
      overproduction of Put had only a small effect on the overall rates of turnover of
      Spd or Spm. There was little effect on the rates of Spd to Spm conversion as well
      as the conversion of Spm into lower polyamines. While Spm was mainly converted
      back to Spd and not terminally degraded, Spd was removed from the cells largely
      through terminal catabolism in both species.

PMID- 24013281
TI  - Certification in performing arts medicine.

PMID- 24013282
TI  - Nutrition and nutritional issues for dancers.
AB  - Proper nutrition, not simply adequate energetic intake, is needed to achieve
      optimal dance performance. However, little scientific research exists concerning
      nutrition in dance, and so, to propose nutritional guidelines for this field,
      recommendations need to be based mainly on studies done in other physically
      active groups. To diminish the risk of energy imbalance and associated disorders,
      dancers must consume at least 30 kcal/kg fat-free mass/day, plus the training
      energy expenditure. For macronutrients, a daily intake of 3 to 5 g
      carbohydrates/kg, 1.2 to 1.7 g protein/kg, and 20 to 35% of energy intake from
      fat can be recommended. Dancers may be at increased risk of poor micronutrient
      status due to their restricted energy intake; micronutrients that deserve concern
      are iron, calcium, and vitamin D. During training, dancers should give special
      attention to fluid and carbohydrate intake in order to maintain optimal
      cognition, motivation, and motor skill performance. For competition/stage
      performance preparation, it is also important to ensure that an adequate dietary
      intake is being achieved. Nutritional supplements that may help in achieving
      specific nutritional goals when dietary intake is inadequate include
      multivitamins and mineral, iron, calcium, and vitamin D supplements, sports
      drinks, sports bars, and liquid meal supplements. Caffeine can also be used as an
      ergogenic aid. It is important that dancers seek dietary advice from qualified
      specialists, since the pressure to maintain a low body weight and low body fat
      levels is high, especially in styles as ballet, and this can lead to an
      unbalanced diet and health problems if not correctly supervised. 

PMID- 24013283
TI  - Pain among professional orchestral musicians: a case study in body culture and
      health psychology.
AB  - BACKGROUND: Professional musicians experience high rates of musculoskeletal pain,
      but only few studies have investigated how this pain is accepted by musicians.
      AIM: To investigate the culture of pain and to explore how professional musicians
      experience and cope with pain. METHODS: Ten semi-structured in-depth interviews
      were conducted; 8 with musicians and 2 with professional elite athletes. In
      addition, a concert and two rehearsals were observed. The audiotaped interviews
      were transcribed verbatim. Configurational analysis was used to interpret the
      material as a whole. RESULTS: Musicians often experience pain as a consequence of
      prolonged repetitive work early in their career. Such pain is compounded by the
      lack of breaks during concerts and rehearsals. Orchestras seldom give
      opportunities for adjustments required for individual instruments, breaks, or
      action to prevent pain. Musicians' strong sense of coherence and the experience
      of pain as integral to their identity have encouraged musicians to develop
      flexible coping strategies. Ignoring pain and potential damage is an accepted
      concomitant to striving for perfection. A musician does not focus on pain but on
      the music. CONCLUSION: For the musician, pain has a significance beyond being
      something that can simply be removed by a practitioner. Pain tells both an
      individual story and a cultural story that is crying out to be heard.

PMID- 24013285
TI  - Isokinetic strength profiles of thigh muscles of modern dancers in relation to
      their experience level.
AB  - The aim of this study was to determine maximal voluntary peak torque (PT), PT%
      body weight (PT%BW), total work (TW), and hamstring/quadriceps ratio (HQR) for
      bilateral and unilateral thigh muscle strength during isokinetic muscle
      contractions in modern dancers in relation to their experience level. METHODS:
      Twenty-two female dancers were divided into two groups: intermediate dancers (ID,
      n=11) and advanced dancers (AD, n=11). Strength tests were performed using the
      Biodex System-III Pro Multijoint System isokinetic dynamometer to determine three
      joint angular velocities (60, 180, 300 degrees /s). RESULTS: During extension,
      ADs exhibited higher ratios in the HQR (p=0.016) on right leg at 300 degrees /s,
      IDs generated greater TW (p=0.042), and within groups, there was a significant
      left-to-right difference in the HQR at 300 degrees /s for ADs (p=0.042). During
      flexion, within groups, the ADs exhibited significant differences between legs
      for both PT (p=0.026) and PT%BW (p=0.022) at 300 degrees /s. CONCLUSION: For both
      groups, the average HQR in all angular velocities was not within the recommended
      range, which is required to prevent injuries; at the same time, unilateral
      muscular imbalances existed. Lower extremities of ADs exhibited asymmetric
      strength patterns at a certain level. Further research should be done to confirm
      the findings of this pilot study.

PMID- 24013284
TI  - Dance partner or dance floor?: exogenous factors resulting in accidents in
      professional dancers.
AB  - OBJECTIVE: Injury prevention in professional dancers is very important due to the
      high risk for acute injuries posing a threat to dancers' careers. Causative
      factors of acute injuries in professional dance can be divided into exogenous and
      endogenous factors. Although both are known in professional dance, there is still
      a lack of data to have a differentiated view. The aim of this study is to analyze
      exogenous factors resulting in work accidents of professional dancers. METHODS:
      The data for the evaluation were obtained from work accident reports (n = 1,438,
      female 722, male 716) from six Berlin Theatres. Evaluation and descriptive
      statistics were conducted by SPSS 18 and Excel 2007. RESULTS: About half (48.5%,
      n = 698) of all work accidents are caused by exogenous factors. The "dance
      partner" is the most common exogenous factor (39.9%), followed by the dance floor
      (28.24%) and props (13.6%). The lower extremity is the most frequent structure
      injured in either sex (male 47.3%, female 61.3%), followed by the upper extremity
      in females (14.6%) and spine in male dancers (19.8%). The stage is the most
      common injury location in both genders (males 63.9%, females 56.8%). Acute
      injuries caused by exogenous factors were particularly sustained during
      performances (males 58.8%, females 50.5%) and during rehearsals (males 33%,
      females 39.9%). CONCLUSION: This study shows the key significance of exogenous
      factors in acute injuries in professional dance. Preserving the dancers' health
      and preventing injuries takes top priority, and therefore, interventions in the
      artistic work cannot be ruled out when preventive measures are implemented.

PMID- 24013286
TI  - Head and shoulder functional changes in flutists.
AB  - AIMS: This study aimed at comparing head posture, symmetry of shoulder muscle
      strength, and posture among developing flutists, professional flutists, and a
      matched control group of singers. METHODS: Measurements of head and scapular
      posture and muscle strength were compared between flutists with <=10 yrs of
      practice (developing flutists, n=9), flutists with >10 years of practice
      (professional flutists, n=9), and singers (n=9). Posture was measured with a
      goniometer and tape measure; strength was assessed with an isokinetic
      dynamometer. RESULTS: Significant differences were found between groups
      concerning forward head posture only; developing flutists showed a higher forward
      head posture compared to the other two groups (p<0.05). No significant
      differences were found for scapular posture or muscle strength. CONCLUSIONS:
      Developing flutists showed significantly more forward head posture. This finding
      supports the need to revise existing music curricula targeting the inclusion of
      compulsory disciplines on music medicine.

PMID- 24013287
TI  - Relationships between depression, anxiety, and pain in a group of university
      music students.
AB  - There is emerging interest in studying the incidence of music-related injuries
      and problems among students. The current study drew on a data set collected from
      287 music majors and minors at a large US midwestern university school of music
      in order to determine if correlations existed between anxiety and/or depression
      and the reported presence of physical pain, and to understand the nature of any
      such relationships. Physical pain symptoms were scored on a scale of 0 (none) to
      10 (excruciating) and summed across 21 body regions. Depression and anxiety
      symptoms were scored as none (0), mild (1), moderate (2), or severe (3), and each
      summed across either 13 symptoms for depression or 8 symptoms for anxiety. The
      potential linear relationship among these variables was evaluated using F-tests
      (as part of ANOVAs) and linear regression parameter estimation techniques. The
      explanatory value of these relationships was evaluated using R2 values. Results
      indicate a clear positive linear relationship between both depression and pain,
      and anxiety and pain. However, the presence of depression and/or anxiety symptoms
      was insufficient to explain variability in pain scores of these participants. 

PMID- 24013288
TI  - Training for sustained performance: moving toward long-term musician development.
AB  - Success in the performing arts, like sports, is dependent upon the acquisition
      and consistent use of a diverse range of skills. In sports, an understanding of
      safe and effective use of the body is required to facilitate long-term
      involvement in that activity. In order to assist athletes to attain their
      performance goals, and ensure healthy and sustained involvement, long-term
      athlete development (LTAD) models have been devised and adapted by professional
      sporting bodies throughout the world. LTAD models emphasize the intellectual,
      emotional, and social development of the athlete, encourage long-term
      participation in physical activities, and enable participants to improve their
      overall health and well-being and increase their life-long participation in
      physical activity. At present there is no such long-term development model for
      musicians. Yet musicians must cope with a multitude of career-related physical
      and mental demands, and performance-related injuries and career burnout are rife
      within the profession. Despite this, musicians' training rarely addresses such
      issues and musicians are left largely to learn about them through either chance
      or accrued experience. This paper discusses key concepts and recommendations in
      LTAD models, together with music-specific research highlighting the need for the
      development of a comprehensive long-term approach to musicians' training. The
      results of a survey of existing music training programs are compared to
      recommendations and the different development stages in LTAD models. Finally,
      implementation science is introduced as a methodological option for identifying
      how best to communicate the body of evidence-based knowledge concerning healthy
      and effective music-making to young student musicians. 

PMID- 24013289
TI  - Worker's compensation for musicians.

PMID- 24013290
TI  - Piano technique.

PMID- 24013291
TI  - Metabolic engineering of Clostridium acetobutylicum for enhanced production of
      butyric acid.
AB  - Clostridium acetobutylicum has been considered as an attractive platform host for
      biorefinery due to its metabolic diversity. Considering its capability to
      overproduce butanol through butyrate, it was thought that butyric acid can also
      be efficiently produced by this bacterium through metabolic engineering. The pta
      ctfB-deficient C. acetobutylicum CEKW, in which genes encoding
      phosphotransacetylase and CoA-transferase were knocked out, was assessed for its
      potential as a butyric acid producer in fermentations with four controlled pH
      values at 5.0, 5.5, 6.0, and 6.4. Butyric acid could be best produced by
      fermentation of the CEKW at pH 6.0, resulting in the highest titer of 26.6 g/l,
      which is 6.4 times higher than that obtained with the wild type. However, due to
      the remaining solventogenic ability of the CEKW, 3.6 g/l solvents were also
      produced. Thus, the CEKW was further engineered by knocking out the adhE1
      encoding aldehyde/alcohol dehydrogenase to prevent solvent production. Batch
      fermentation of the resulting C. acetobutylicum HCEKW at pH 6.0 showed increased
      butyric acid production to 30.8 g/l with a ratio of butyric-to-acetic acid
      (BA/AA) of 6.6 g/g and a productivity of 0.72 g/l/h from 86.9 g/l glucose, while
      negligible solvent (0.8 g/l ethanol only) was produced. The butyric acid titer,
      BA/AA ratio, and productivity obtained in this study were the highest values
      reported for C. acetobutylicum, and the BA/AA ratio and productivity were also
      comparable to those of native butyric acid producer Clostridium tyrobutyricum.
      These results suggested that the simultaneous deletion of the pta-ctfB-adhE1 in
      C. acetobutylicum resulted in metabolic switch from biphasic to acidogenic
      fermentation, which enhanced butyric acid production.

PMID- 24013292
TI  - Pb(II) and Cr(VI) sorption by biochars pyrolyzed from the municipal wastewater
      sludge under different heating conditions.
AB  - To optimize the pyrolysis process of municipal wastewater sludge for metal
      sorption, this study investigated the characteristics of the produced biochar
      under different heating conditions with particular interest in Pb(II) or Cr(VI)
      sorption. Results indicate that the biochar pyrolyzed at 400  degrees C for 2 h
      obtained the largest BET surface area and was rich of organic functional groups,
      owning the highest Pb(II) (at pH 5.0) and Cr(VI) (at pH 2.0) sorption capacity.
      The Pb sorption is dominated by the rate-limited chemical processes, and a longer
      residence during pyrolysis significantly reinforces its sorption bonds. The
      Cr(VI) sorption is highly pH-dependent, and the optimal occurs at pH 2, where the
      transformation of Cr(VI) to Cr(III) makes a significant contribution as confirmed
      by the XPS spectra. Similarly, a longer residence during pyrolysis also
      facilitates the Cr(VI) sorption in terms of capacity and affinity, likely due to
      the greater reducing potential of biochar.

PMID- 24013293
TI  - A kinetic study of biohydrogen production from glucose, molasses and cheese whey
      by suspended and attached cells of Thermotoga neapolitana.
AB  - Batch tests of H2 production from glucose, molasses and cheese whey by suspended
      and immobilized cells of Thermotoga neapolitana were conducted to develop a
      kinetic model of the process. H2 production was inhibited by neither H2 (up to
      0.7 mg L(-1)) nor O2 (up to 0.2 mg L(-1)). The H2 specific rates obtained at
      different substrate concentrations were successfully interpolated with Andrew's
      inhibition model. With glucose and molasses, biofilms performed better than
      suspended cells. The suspended-cell process was successfully scaled-up to a 19-L
      bioreactor. Assays co-fed with molasses and cheese whey led to higher H2
      productivities and H2/substrate yields than the single-substrate tests. The
      simulation of the suspended-cell continuous-flow process indicated the potential
      attainment of H2 productivities higher than those of the batch tests (up to 3.6
      mmol H2 h(-1) L(-1) for molasses and 0.67 mmol H2 h(-1) L(-1) for cheese whey)
      and allowed the identification of the optimal dilution rate.

PMID- 24013294
TI  - Mixotrophic growth of Phaeodactylum tricornutum on fructose and glycerol in fed
      batch and semi-continuous modes.
AB  - Mixotrophic cultures of Phaeodactylum tricornutum were carried out in bubble
      columns using fructose and glycerol in indoor fed-batch and semi-continuous
      modes. In the fed-batch cultures, different nutrient-addition strategies,
      combined with stepwise increments in the light intensity, were assayed. It was
      found that glycerol promoted significantly higher biomass productivity than
      fructose. A glycerol-induced photoinhibition that arrested the growth of P.
      tricornutun was also observed. As this was considered a limitation as regards
      transferring the fed-batch mode to outdoor conditions, this information was used
      to culture P. tricornutum in semi-continuous mode. Similar glycerol-induced
      photoinhibition was not observed in these cultures, even at highest dilution
      rates. Although the highest biomass (1.5 g L(-1) d(-1)) and EPA (40 mg L(-1) d(
      1)) productivities found in the semi-continuous cultures were lower than those
      obtained photoautotrophically in outdoor photobioreactors, the findings showed
      that semi-continuous mode was an excellent candidate for transferring mixotrophic
      culture to an outdoor setting.

PMID- 24013295
TI  - Comparison for the compositions of fast and slow pyrolysis oils by NMR
      characterization.
AB  - The pyrolysis of softwood (SW) kraft lignin and pine wood in different pyrolysis
      systems were examined at 400, 500 and 600  degrees C. NMR including quantitative
      (13)C and Heteronuclear Single-Quantum Correlation (HSQC)-NMR, and Gel Permeation
      Chromatography (GPC) were used to characterize various pyrolysis oils. The
      content of methoxyl groups decreased by 76% for pine wood and 70% for lignin when
      using fast pyrolysis system. The carbonyl groups also decreased by 76% and nearly
      completely eliminated in 600  degrees C pine wood fast pyrolysis oil. Compared to
      the slow pyrolysis process, fast pyrolysis process was found to improve the
      cleavage of methoxyl groups, aliphatic CC bonds and carbonyl groups and produce
      more polyaromatic hydrocarbons (PAH) from lignin and aliphatic CO bonds from
      carbohydrates. Another remarkable difference between fast and slow pyrolysis oils
      was the molecular weight of fast pyrolysis oils increased by 85-112% for pine
      wood and 104-112% for lignin.

PMID- 24013296
TI  - Electrocatalytic hydrogen evolution from neutral water by molecular cobalt
      tripyridine-diamine complexes.
AB  - A cobalt complex with a tripyridine-diamine pentadentate ligand was found to be a
      highly active catalyst for electrochemical H2 production from neutral water, with
      an activity of 860 mol H2 (mol cat)(-1) h(-1) (cm(2) Hg)(-1) over 60 h CPE
      experiment at -1.25 V in a pH 7 phosphate buffer solution, without considerable
      deactivation. 

PMID- 24013297
TI  - Liberty has its responsibilities: holding non-vaccinators liable for the harm
      they do.
AB  - David Ropiek in his useful essay on how society should respond to the risks
      created by those who choose not to vaccinate themselves or their children does a
      very useful job of identifying the enormous costs in money and health that non
      vaccinators create. He also pinpoints the many factors that drive vaccine
      resistance locating them not in a misunderstanding of the facts but, in fears and
      negative emotions. It is important to pay attention to his message since
      frequently those who want to try to reduce vaccine hesitation or outright non
      vaccination behavior put their faith in education and resort to an invocation of
      the facts about the value of vaccines when it is fear and emotions that must be
      addressed.

PMID- 24013299
TI  - Advances in diabetes prevention and management through the life's work of Arthur
      Krosnick, MD.

PMID- 24013300
TI  - History of diabetes.

PMID- 24013298
TI  - Dysbiosis of salivary microbiota in inflammatory bowel disease and its
      association with oral immunological biomarkers.
AB  - Analysis of microbiota in various biological and environmental samples under a
      variety of conditions has recently become more practical due to remarkable
      advances in next-generation sequencing. Changes leading to specific biological
      states including some of the more complex diseases can now be characterized with
      relative ease. It is known that gut microbiota is involved in the pathogenesis of
      inflammatory bowel disease (IBD), mainly Crohn's disease and ulcerative colitis,
      exhibiting symptoms in the gastrointestinal tract. Recent studies also showed
      increased frequency of oral manifestations among IBD patients, indicating
      aberrations in the oral microbiota. Based on these observations, we analyzed the
      composition of salivary microbiota of 35 IBD patients by 454 pyrosequencing of
      the bacterial 16S rRNA gene and compared it with that of 24 healthy controls
      (HCs). The results showed that Bacteroidetes was significantly increased with a
      concurrent decrease in Proteobacteria in the salivary microbiota of IBD patients.
      The dominant genera, Streptococcus, Prevotella, Neisseria, Haemophilus,
      Veillonella, and Gemella, were found to largely contribute to dysbiosis
      (dysbacteriosis) observed in the salivary microbiota of IBD patients. Analysis of
      immunological biomarkers in the saliva of IBD patients showed elevated levels of
      many inflammatory cytokines and immunoglobulin A, and a lower lysozyme level. A
      strong correlation was shown between lysozyme and IL-1beta levels and the
      relative abundance of Streptococcus, Prevotella, Haemophilus and Veillonella. Our
      data demonstrate that dysbiosis of salivary microbiota is associated with
      inflammatory responses in IBD patients, suggesting that it is possibly linked to
      dysbiosis of their gut microbiota. 

PMID- 24013302
TI  - Legislative brief: New Jersey legislatures address diabetes & childhood obesity.

PMID- 24013303
TI  - Reducing the impact of diabetes in New Jersey.

PMID- 24013304
TI  - Patient-centric tools for better diabetes self-management.

PMID- 24013305
TI  - The heart of diabetes.

PMID- 24013306
TI  - General approach to the type 2 diabetic patient.

PMID- 24013307
TI  - Stay hungry for knowledge.

PMID- 24013308
TI  - A young adult's perspective: an encouraging story for young diabetics.

PMID- 24013309
TI  - Talking about diabetes.

PMID- 24013310
TI  - ZnSe nanowire/Si p-n heterojunctions: device construction and optoelectronic
      applications.
AB  - Nano-heterojunctions will play essential roles in future nano-electronic and nano
      optoelectronic devices. However, their extensive applications are impeded by the
      complicated multi-step growth method involved and the requirements for precise
      nanowire (NW) positioning/alignment. Here, we develop a facile method to
      fabricate zinc selenide NW (ZnSeNW)/silicon p-n heterojunctions by transferring
      the p-type ZnSeNWs onto a SiO2/Si substrate with pre-defined Si windows; the
      physical contact of the NWs with the Si substrate via van der Waals force leads
      to the formation of heterojunctions. Electrical measurements on the
      heterojunctions reveal their excellent diode characteristics with a relatively
      small ideality factor of ~1.95, high rectification ratio of ~106, and low turn-on
      voltage of ~0.9 V. Moreover, heterojunction field-effect transistors are
      constructed based on the p-ZnSeNWs and show remarkable performance enhancement
      compared to the device counterparts with a metal-oxide-semiconductor field-effect
      transistor structure. The enhanced gate coupling between the NW conduction
      channel and the heterojunction gate is believed to be responsible for the high
      device performance. Significantly, under AM 1.5G light illumination, the
      heterojunctions exhibit pronounced photovoltaic behavior, yielding a power
      conversion efficiency of ~1.8%. Our results demonstrate the great potential of
      ZnSeNW/Si p-n heterojunctions in high-performance nano-device applications.

PMID- 24013311
TI  - Identification of bridged CO2 binding in a Prussian blue analogue using neutron
      powder diffraction.
AB  - Neutron powder diffraction measurements were carried out on the evacuated and CO2
      loaded Prussian blue analogue, Fe3[Co(CN)6]2, identifying two distinct CO2
      adsorption sites: site A, in which CO2 uniquely bridges between two bare-metal
      sites, and site B, in which it interacts in a face capping motif. The saturation
      of site A at low loadings of CO2 demonstrates the favourable nature of the
      interaction of CO2 with bare-metal sites within the material. 

PMID- 24013312
TI  - Biography Tadanori Tomita: ISPN president 2011-2012.

PMID- 24013314
TI  - Spinal dysraphism.
AB  - In the last decade there have been significant improvements in all the fields of
      management of patients with spinal dysraphism, which have increased dramatically
      the quality of life of these children. Prevention of spina bifida with food
      fortification is becoming increasingly practiced worldwide. As result, in many
      parts of the world the frequency of myelomeningocele has decreased. Intrauterine
      closure of myelomeningocele has been attempted in many institutions with variable
      results. While it is still at the sphere of experimental therapy, it is
      reasonable to anticipate progress in this field in the next decade. Antenatal MR
      imaging is already providing very high level of detail even before the child is
      born. This creates new ethical dilemmas and requires additional care, but has
      improved significantly the overall management of patients and their families.
      Further improvements are anticipated in this field. Management of neuropathic
      bladder has improved significantly in the last decade and is anticipated to play
      an increasing role in the long term follow up. Surgery for spinal cord tethering
      in all its forms has improved in the last decade, with far more chances of
      complete untethering now in comparison to 10-15 years ago, with the use of micro
      neurosurgical techniques and intraoperative monitoring. It is reasonable to
      expect that in the next decade, intraoperative neurophysiological monitoring
      during spinal cord surgery will become mandatory. In the 2013 Annual Special
      Issue we have assembled a team of authors distinguished in their fields, who
      bring us up to date with all the latest developments. 

PMID- 24013313
TI  - Pediatric neurosurgery-science, art, and humility: reflection of personal
      experience.

PMID- 24013315
TI  - Genetic studies of myelomeningocele.
AB  - INTRODUCTION: Myelomeningocele is one of the major congenital malformations
      involving the central nervous system. It is caused by a disruption of the neural
      tube closure, which is completed at 3-4 weeks of gestation. DISCUSSION:
      Multidisciplinary approach is necessary to treat and support this malformation
      which is a huge burden to the patient, family, and the society. This is a
      characteristic anomaly that it is known that taking folic acid during the
      periconceptional period, it is possible to reduce the risk of having a neural
      tube defect (NTD). Although folate fortification had dramatically reduced the
      incidence, it was not possible to diminish the risk. To date, many studies have
      been conducted focusing on candidate genes related to folate and glucose
      metabolism. We will describe a brief review of genetic etiology of candidate
      genes of metabolic pathways of folate and glucose, animal models of NTDs, and
      finally recent studies of microRNA.

PMID- 24013316
TI  - Folate and epigenetic mechanisms in neural tube development and defects.
AB  - INTRODUCTION: Multiple genetic and epigenetic factors involved in central nervous
      system (CNS) development influence the incidence of neural tube defects (NTDs).
      DISCUSSION: The beneficial effect of periconceptional folic acid on NTD
      prevention denotes a vital role for the single-carbon biochemical pathway in NTD
      genesis. Indeed, NTDs are associated with polymorphisms in a diversity of genes
      that encode folate pathway enzymes. Recent evidence suggests that CNS development
      and function, and consequently NTDs, are also associated with epigenetic
      mechanisms, many of which participate in the folate cycle and its input and
      output pathways. We provide an overview with select examples drawn from the
      authors' research.

PMID- 24013317
TI  - Experimental models of spinal open neural tube defect and Chiari type II
      malformation.
AB  - INTRODUCTION: Experimental animal models are essential for investigation of the
      pathoembryogenesis, pathophysiology, and management strategy of spinal open
      neural tube defect (ONTD) and its associated anomalies including Chiari type II
      malformation. Genetic, chemical/nutrient, and surgical models have been widely
      used for a variety of purposes. The aim of this article is to review the
      representative animal models of spinal ONTD and associated Chiari type II
      malformation with respect to their advantages and disadvantages. DISCUSSION:
      Among them, the surgical model was described in detail because it is familiar to
      neurosurgeons and it is used for evaluations of prenatal repair of spinal ONTDs.
      The surgical model also has advantages because it allows quantitative analysis of
      the lesions. A description of our previous studies on spinal ONTDs using a chick
      surgical model is presented as an example.

PMID- 24013318
TI  - Closed neural tube defects in children with caudal regression.
AB  - INTRODUCTION: Infants born with caudal regression (CR) may have serious
      multisystem abnormalities that require prompt attention in the neonatal period.
      The presence of a closed neural tube defect (NTD) that can lead to future
      neurological deterioration may be overlooked. MATERIALS AND METHODS: An IRB
      approved retrospective review was conducted among patients with CR and a closed
      NTD that underwent neurosurgical operative intervention between 1996 and 2012 at
      a single institution. RESULTS: Twenty-two patients who met the above criteria
      were identified. Of this group, 13 were identified and surgically addressed in
      the first year of life; however, nine additional children were diagnosed with a
      closed NTD after a year of age with progressive neurological deterioration. Of
      the entire group, none had any cutaneous markers that are often seen with a
      closed NTD. CONCLUSION: The frequent finding of a closed NTD associated with
      major CR abnormalities, even in the absence of any cutaneous markers for
      dysraphism, recommends that infants with CR undergo a MRI screening in early
      infancy to exclude the presence of a closed NTD.

PMID- 24013319
TI  - Limited dorsal myeloschisis: a not-so-rare form of primary neurulation defect.
AB  - PURPOSE: Limited dorsal myeloschisis (LDM) is a distinctive form of spinal
      dysraphism characterized by two constant features: a focal "closed" midline skin
      defect and a fibroneural stalk that links the skin lesion to the underlying cord.
      The embryogenesis is hypothesized to be incomplete disjunction between cutaneous
      and neural ectoderms, thus preventing complete midline skin closure and allowing
      persistence of a physical link (fibroneural stalk) between the disjunction site
      and the dorsal neural tube. OBJECTIVE: We utilize the experience gained from the
      management of 63 patients with LDM to illustrate these features. METHODS: All
      patients were studied with MRI or CT myelogram, operated on, and followed for a
      mean of 9.4 years. RESULTS: There were 11 cervical, 16 thoracic, 8 thoracolumbar,
      and 28 lumbar lesions. Two main types of skin lesion were: saccular (26 patients;
      consisting of a skin base cerebrospinal fluid sac topped with squamous epithelial
      dome or a thin membranous sac) and nonsaccular (37 patients; with a flat or
      sunken squamous epithelial crater or pit). The internal structure of a saccular
      LDM could be a basal neural nodule, a stalk that inserts on the dome, or a
      segmental myelocystocoele. In nonsaccular LDMs, the fibroneural stalk has
      variable thickness and complexity. All fibroneural stalks contain glioneuronal
      tissues accompanied by variable quantities of nerves and mesodermal derivatives.
      In all LDMs, the fibroneural stalk was tethering the cord. Twenty-nine patients
      had neurological deficits. There was a positive correlation between neurological
      grade and age suggesting progression with chronicity. Treatment consisted of
      detaching the stalk from the cord. Most patients improved or remained stable.
      LDMs were associated with three other dysraphic malformations in more than
      coincidental frequencies: six LDMs were contiguous with dorsal lipomas, four LDMs
      shared the same tract or traveled in parallel with a dermal sinus tract, and
      seven LDMs were related to a split cord malformation. The embryogenetic
      implications of these associations are discussed. CONCLUSION: LDM is a
      distinctive clinicopathological entity and a tethering lesion with characteristic
      external and internal features. We propose a new classification incorporating
      both saccular and flat lesions.

PMID- 24013320
TI  - Surgical treatment of complex spinal cord lipomas.
AB  - PURPOSE: This paper shows the long-term benefits of total/near-total resection of
      complex spinal cord lipomas and meticulous reconstruction of the neural placode,
      and specifically, its advantage over partial resection, and over non-surgical
      treatment for the subset of children with asymptomatic virgin lipomas. METHODS:
      The technique of total resection and placode reconstruction, together with
      technical nuances, are described in detail. We added 77 patients with complex
      lipomas to our original lipoma series published in 2009 and 2010, to a total of
      315 patients who had had total or near-total resection and followed for a span of
      20 years. Long-term outcome is measured by overall progression-free survival
      (PFS) with the Kaplan-Meier analysis, and by subgroup Cox proportional recurrence
      hazard analysis for the influence on outcome of 4 predictor variables of lipoma
      type, presence of symptoms, prior surgery, and post-operative cord-sac ratio.
      These results are compared to an age-matched, lesion-matched series of 116
      patients who underwent partial lipoma resection over 11 years. The results for
      total resection is also compared to two large published series of asymptomatic
      lipomas followed without surgery over 9 to 10 years, to determine whether
      prophylactic total resection confers better long-term protection over
      conservative treatment for children with asymptomatic lipomas.. RESULTS: The PFS
      after total resection for all lipoma types and clinical subgroups is 88.1 % over
      20 years versus 34.6 % for partial resection at 10.5 years (p < 0.0001). Culling
      only the asymptomatic patients with virgin (previously unoperated) lipomas, the
      PFS for prophylactic total resection for this subgroup rose to 98.8 % over 20
      years, versus 67 % at 9 years for one group of non-surgical treatment and 60 % at
      10 years for another group of conservative treatment. Our own as well as other
      published results of partial resection also compare poorly to non-surgical
      treatment for the subset of asymptomatic virgin lipomas. Multivariate subgroup
      analyses show that cord-sac ratio is the only independent variable that predicts
      outcome, with a 96.9 % PFS for ratio < 30 % (loosest sac), 86.2 % for ratio
      between 30 and 50 %, and 78.3 % for ratio > 50 % (tightest sac), and a threefold
      increase in recurrence hazard for high ratios (p = 0.0009). Pre-operative patient
      profiling using multiple correspondence analysis shows the ideal patient for
      total resection is a child less than 2 years old with a virgin asymptomatic
      lipoma, who, with a PFS of 99.2 %, is virtually cured by total resection.
      CONCLUSION: Total/near-total resection of complex lipomas and complete
      reconstruction of the neural placode achieves far better long-term protection
      against symptomatic recurrence than partial resection for all lesions; and for
      the subset of asymptomatic virgin lipomas, also better than non-surgical
      treatment. Partial resection in many cases produces worse outcome than
      conservative treatment for asymptomatic lesions.

PMID- 24013322
TI  - Complex forms of spinal dysraphism.
AB  - INTRODUCTION: Spinal dysraphisms are a heterogeneous group of congenital
      malformations involving the bony component of vertebrae or spinal cord or both.
      Simple forms include the contiguous, solitary malformations such as
      myelomeningocele and diastematomyelia, and can be either aperta or occulta type.
      MATERIAL: Complex forms include various types of spinal malformations occurring
      in combination, one type of malformations occurring at multiple levels in
      noncontiguous manner or spinal dysraphisms with other organ anomalies. Anomalous
      development in gastrulation, primary neurulation, and secondary neurulation stage
      in variable proportions give rise to these types of complex malformations. These
      cases can be diagnosed postnatally in early infancy by the strong clinical
      suspicion, supplemented by whole spinal axis and cranial magnetic resonance
      imaging (MRI) screening, to detect any occult spinal dysraphisms like split cord
      malformations, neurenteric cyst, lipoma, or cranial anomalies like Chiari
      malformations and hydrocephalus. Computed tomography and MRI are the gold
      standard to detect bony anomalies and cord malformations, respectively. Complex
      spinal dysraphisms, to our mind, should always be tried to be corrected in single
      operative stage, however, in case of ruptured defects, correction through
      multiple operations can be considered. DISCUSSION: Overall, prognosis of complex
      forms of spinal dysraphism is poor in comparison to their simple forms and
      depends on preoperative neurological status and the nature of complex dyraphism.
      We discuss the classification, embryogenesis, investigation, and treatment
      protocol with review of literature of such complex anomalies.

PMID- 24013321
TI  - Split cord malformation types I and II: a personal series of 131 patients.
AB  - PURPOSE: A personal series of 131 patients with split cord malformation (SCM)
      operated on is presented. METHODS: Age, gender, symptoms and signs, radiological
      and operative findings, complications, associated anomalies, outcome, and
      pathological specimens were analyzed. RESULTS: There were 88 girls (73 %) and 43
      boys (27 %). The female predominance was slightly more remarkable in type I SCMs
      than in type II SCMs. The presenting symptoms can be summarized as skin lesions,
      spina bifida aperta, scoliosis or kyphoscoliosis, sphincter disturbance, foot
      deformities and weakness, and/or atrophy in the lower extremities. The ages of
      patients with neurological deficits and orthopedic deformities were significantly
      older than those without deficits (P = 0.030). The duration of symptoms was
      longer in the patients with neurological deficits and orthopedic deformities than
      that in those without deficits (P = 0.00095). In six patients, composite SCMs
      were present. Only one patient with a type II SCM did not have an associated
      spinal cord lesion. A type I SCM was more frequently encountered in patients with
      spina bifida (P < 0.0005). Transient postoperative complications were seen in 29
      patients (22 %). There was no permanent complication. Retethered cord syndrome
      developed in five patients with a type I SCM. CONCLUSIONS: The risk of
      neurological and orthopedic deficits increases with the age of the patient. The
      risk of permanent deficit after surgery is very low. The whole spine must be
      examined for additional lesions. All patients should be surgically treated when
      diagnosed, especially before the development of orthopedic and neurological
      manifestations, and all associated lesions should also be treated at the same
      session.

PMID- 24013323
TI  - Prevention of myelomeningocele: African perspectives.
AB  - BACKGROUND: The prevention of neural tube defects (NTDs) is now an issue of major
      public health concern. Myelomeningocele, the most common NTD, often results in
      severe disabilities and may be life threatening. In Africa, there is little
      awareness of the NTDs, and most African countries lag behind in the global
      efforts at preventing them. PURPOSE: Following a review of global literature, we
      discuss the burden of myelomeningocele on the society and the current state of
      its prevention with an emphasis on Africa within the global context. The
      realization that folate supplementation reduces the occurrence of NTDs by as much
      as 85 % offers an opportunity to promote global reduction in the incidence of
      NTDs through (1) effective folate supplementation strategies combined with (2)
      secondary prevention using prenatal detection and termination of NTD pregnancies
      within respective national legal frameworks. We call attention to the poor state
      of understanding of NTDs in Africa and the alarming rarity of policies to prevent
      the condition in the continent. CONCLUSIONS: The understanding of the
      contributions of folate deficiency to the causation of NTDs has enabled
      appropriate, though still inadequate, preventive measures to be taken in several
      countries. We call on African governments and the international community to
      rapidly promote policies aimed at making fortification of wheat (and or other
      substitute staple foods) with folic acid universally available.

PMID- 24013324
TI  - Prenatal diagnosis of spinal dysraphism.
AB  - INTRODUCTION: Since intrauterine repair of open spinal dysraphism have
      demonstrated promising results, it has become crucial to accurately define the
      various prenatal pathologies. The embryogenesis of spinal dysraphism according to
      a clinical neuroradiological classification is reviewed, with special emphasis on
      the recent advances in prenatal ultrasound (US), such as high-frequency linear
      transducers and three-dimensional imaging. FUNDINGS: The role of magnetic
      resonance imaging (MRI) of the fetus as a complementary tool for delineating
      complex fetal spinal anomalies and further defining associated central nervous
      system (CNS) anomalies is explored. Differentiation between normal appearance of
      the fetal spine and the wide range of congenital neural tube defects are
      demonstrated in both modalities with special emphasis on their complementary role
      in the accurate diagnosis of neural tube defects.

PMID- 24013325
TI  - Primary and secondary management of the Chiari II malformation in children with
      myelomeningocele.
AB  - OBJECT: Chiari malformation type II is almost exclusively found in patients with
      open spinal dysraphism. Etiology and pathophysiology are not yet completely
      understood, and management guidelines regarding the best follow-up and treatment
      of this pathological entity do not exist. In order to assess essential management
      aspects, literature and a series of secondary neurosurgical interventions in
      Chiari II patients have been reviewed. METHODS: A literature review regarding
      etiology, diagnostics, pathophysiology, and management of Chiari malformation
      type II (CMII) and a retrospective evaluation of a series (2009-2012) of
      secondary interventions in Chiari II patients have been performed. Inclusion
      criteria were ICD for myelomeningocele with or without hydrocephalus and ICD for
      Chiari malformation and neurosurgical OR procedure. Evaluated parameters were:
      patient demographics, primary management, secondary neurosurgical operations
      (cranio-cervical decompression, shunt revision, myelolysis) as well as specific
      findings pre- and postoperatively. Essential results from literature review and
      patients' series are compiled in order to define management recommendations.
      RESULTS: Fifty patients (28 f, 22 m; mean age, 7.1 years (range, 0.5-26 years))
      with myelomeningocele-associated Chiari malformation type II were operated on
      between 2009 and 2012. Twenty-four patients had syringomyelia and scoliosis each,
      and 12 suffered from both. Orthopedic surgery for scoliosis or kyphosis had been
      performed in 13 cases. Shunt revision was performed in 38 cases, myelolysis in
      17, and decompression of the foramen magnum in 14 (28 %). After a mean follow-up
      of 1.9 years, syringomyelia decreased from 24 to 16 cases. There was a
      postoperative reduction of neck pain (one third), sensorimotor (two fifths), and
      cranial nerve deficits (one half). CSF flow at the foramen magnum did not change
      visibly after surgery. Ventricular size improved in about half of the patients.
      Slit-like ventricles were found in nine (6 pre-surgical) and enlarged ventricles
      in nine (23 pre-surgical). Complication rate was 6 % (3/50) per cases, and no
      patient died or deteriorated neurologically after surgery. CONCLUSION: CMII
      related management guidelines are not well defined, since clinical constellations
      and presentations are varying. Often associated findings are syringomyelia,
      hydrocephalus, and scoliosis, and symptomatic CMII may be triggered by more than
      one underlying condition. According to literature and clinical experience,
      management recommendations can be defined. The most important finding is that
      hydrocephalus is often involved in symptomatic CMII and must always be considered
      first in any symptomatic patient. Intrinsic brain stem dysfunctions cannot be
      treated surgically, and monitoring of vital functions is sometimes the only
      clinical means that can be offered to the patient. Knowledge of the complex
      background has led to improved follow-up programs for the affected children and
      thus also improved longtime survival.

PMID- 24013326
TI  - Surgical decompression without dural opening for symptomatic Chiari type II
      malformation in young infants.
AB  - OBJECTIVE: Prompt surgical decompression for symptomatic Chiari type II
      malformation in neonates and young infants has been reported to be effective.
      However, the optimal operative method has been arguable. The authors present
      their experiences with surgical decompression without dural opening. METHODS: We
      retrospectively analyzed surgical results of patients with symptomatic Chiari
      type II malformation. The charts were reviewed for demographic data, clinical
      presentation, surgical procedures, and clinical outcomes. RESULTS: Ten
      consecutive patients with symptomatic Chiari type II malformation were surgically
      treated from August 2004 to December 2012. The mean age was 3.5 months. The
      median interval between onset of symptoms and surgery was 19.5 days. Three
      patients were treated by upper cervical bone decompression with dural opening and
      duraplasty. Seven patients were treated by upper cervical bone decompression with
      delamination of the outer layer of the dura. There were no perioperative
      complications. The mean follow-up period was 55 months (range 3-102 months). All
      10 patients remain alive. In patients with dural opening, one patient showed
      complete recovery, and two patients had residual deficits and required a
      tracheostomy, one with ventilator support and the other with home oxygen therapy.
      In patients without dural opening, six patients (85 %) showed complete or nearly
      complete recovery, and one patient required tracheostomy and home oxygen therapy.
      CONCLUSION: Upper cervical bone decompression with delamination of the outer
      layer of the dura can be a safe and effective treatment for symptomatic Chiari
      type II malformation in neonates and young infants.

PMID- 24013327
TI  - Myelomeningocele: the management of the associated hydrocephalus.
AB  - BACKGROUND: The pathogenesis of the hydrocephalus associated with
      myelomeningocele (MMC) has been the subject of an extensive number of studies.
      The contemporary reduction of the incidence of the Chiari II malformation and of
      the associated active hydrocephalus after closure of the spinal defect in utero
      is in line with previous studies suggesting a prominent role of the posterior
      cranial fossa abnormalities, where even the increased venous pressure might be at
      least mostly a consequence of the constriction of the posterior cranial fossa
      structures. Pure absorptive abnormalities however coexist, the main ones
      documented to be abnormal cisternal spaces and peculiar cerebrospinal fluid
      chemical features. MATERIALS AND METHODS: We reviewed the pertinent literature
      concerning the pathogenesis and management of the hydrocephalus associated to
      MMC. We also reviewed our personal experience in managing the hydrocephalus in
      such patients through an endoscopic third ventriculostomy. RESULTS AND
      CONCLUSIONS: The literature review demonstrated an overall reduction in more
      recent series of children with MMC needing to be treated for the associated
      hydrocephalus postnatally, questioning the role of the prenatal care of the
      disease in this context. Less severe conditions and a more conservative
      neurosurgical attitude have certainly contributed to the reduction of the
      reported active postnatal hydrocephalus rate. Long-term cognitive evaluation of
      the children with MMC that we managed with an endoscopic third
      ventriculocisternostomy (ETV) as primary as well as secondary procedure did not
      demonstrate significant differences in the outcome compared with non-complicated
      extrathecally shunted children, favouring ETV as a valuable option in this subset
      of patients.

PMID- 24013328
TI  - Neuro-orthopaedic conditions in spina bifida: natural course and their management
      and long-term outcomes.
AB  - INTRODUCTION: Management of spina bifida is a complex issue with various systems
      of the body involved either directly or indirectly. DISCUSSION: Deformities of
      the bone and joints (especially spine and lower limbs) play a significant role in
      causation of deficits in the child. Management of these deficits require a
      focused, specialised and multidisciplinary approach with orthopaedician,
      physiotherapist, intensivist and psychologist apart from neurosurgeon playing an
      important part. To manage these deformities, one needs to understand the
      pathophysiology of causation of these defects. The corrective surgical
      intervention ranges from a simple release of contracture to highly complex spinal
      instrumentations. CONCLUSION: We reviewed the literature and have shared our
      experience on this aspect of spina bifida.

PMID- 24013329
TI  - Urodynamic studies in spinal cord tethering.
AB  - INTRODUCTION: Tethered cord syndrome (TCS) is of particular interest to
      urologists through its effects on the function of the lower urinary tract.
      Tethering of the spinal cord can result in bladder dysfunction with multiple
      manifestations, clinically raging from urinary retention and detrusor under
      activity to urinary incontinence, over-activity of the detrusor, and sphincter
      dysfunction. Goals of management include protecting renal function and preserving
      patient quality of life. METHODS: Evaluation of a TCS patient with urinary
      complaints begins with a thorough history and physical examination. Further
      characterization of urinary symptoms with a voiding diary provides vital
      information that helps to direct treatment while engaging the patient and family
      in the treatment plan. Urodynamic studies then provide key diagnostic data
      regarding bladder function, bladder outlet resistance, and urinary sphincter
      function. In the pediatric population, particular care must be paid to counseling
      patients and their families prior to the procedure to alleviate the often
      considerable anxiety associated with an invasive procedure. CONCLUSION: The
      armamentarium for management of neurogenic bladder associated with TCS includes
      behavioral training, biofeedback therapy, medications, patient-performed
      procedures, and surgical intervention. The choice of intervention depends on the
      patient's symptoms, urodynamic findings, and patient and family preferences. The
      primary problem of TCS should be addressed first through detethering, and then
      the urological team can use progressively more aggressive therapies as necessary.
      Interpretation and treatment by a dedicated, specialized, multidisciplinary team
      that includes the pediatric urologist, pediatric neurosurgeon and dedicated nurse
      practitioner, is critical for successful treatment.

PMID- 24013330
TI  - Recurrent tethered cord: radiological investigation and management.
AB  - INTRODUCTION: Recurrent tethered cord (RTC) is almost the rule after the repair
      of myelomeningocele and quite frequent after the repair of lipomyelomeningocele,
      resulting from the adhesions of the placode within a too narrow spinal canal.
      About one-third of patients with myelomeningocele and 10 % of those with spinal
      lipoma develop symptomatic RTC, mainly caused by the ischemic-metabolic injuries
      due to the cord stretching. The goal of this review is to provide information
      about the pathophysiology, the radiological picture, and the management of RTV
      according to the pertinent literature and the authors' experience. RADIOLOGICAL
      INVESTIGATION: The magnetic resonance imaging (MRI) picture is characterized by a
      low position of the conus and by tethering of the spinal cord to the subcutaneous
      scar or to the inner surface of the spinal canal. The radiological work-up always
      includes brain MRI, to rule out other possible causes of late neurological
      deterioration (as shunt malfunction), and MRI of the whole spinal cord, to detect
      possible associated lesions (syringomyelia, dermoids, etc.). X-rays and/or
      computed tomography scan of the spine is required for the assessment of scoliosis
      or other bony malformations. MANAGEMENT: The surgical treatment is planned after
      a multidisciplinary neurological, urological, orthopedic, physiatric, and
      radiological evaluation. The surgical detethering is carried out cautiously,
      possibly with electrophysiological intraoperative monitoring. Surgery ensures
      improvement or stability of the clinical picture in 70-80 % of cases, the
      remaining 20-30 % of patients needing multiple operations for their recovery.
      Complications may affect up to one-third of operated patients, being mainly
      represented by CSF leak, pseudomeningocele, and shunt malfunction.

PMID- 24013331
TI  - Intraoperative neurophysiology in tethered cord surgery: techniques and results.
AB  - INTRODUCTION: Intraoperative neurophysiologic monitoring (IOM) is nowadays
      extensively used to minimize neurological morbidity in tethered cord surgery. Our
      goal is to describe and discuss the standard IOM techniques used during these
      surgical procedures and to summarize our clinical experience using a multimodal
      IOM approach. MATERIAL AND METHODS: Neurophysiological mapping of the conus-cauda
      is performed through direct stimulation of these structures and bilateral
      recording from segmental target muscles. While mapping identifies ambiguous
      neural structures, their functional integrity during surgery can be assessed by
      monitoring techniques only, such as somatosensory evoked potentials (SEPs),
      transcranial motor-evoked potentials (MEPs) from the limb muscles and anal
      sphincters, and the bulbocavernosus reflex (BCR). RESULTS: Between 2002 and 2012,
      we performed 48 surgical procedures in 47 patients with a tethered cord secondary
      to a variety of spinal dysraphisms. The monitorability rate was 84 % for SEPs, 97
      % for limb muscle MEPs, 74 % for the anal sphincter MEPs, and 59 % for the BCR.
      In all patients but one, SEP, MEP, and BCR remained stable during surgery.
      Postoperatively, two out of 47 patients presented a significant-though transient
      neurological worsening. In six patients, an unexpected muscle response was evoked
      by stimulating tissue macroscopically considered as not functional. CONCLUSIONS:
      Mapping techniques allow identifying and sparing functional neural tissue and
      vice versa to cut nonfunctional structures that may contribute to cord tethering.
      Monitoring techniques, MEP and BCR in particular, improve the reliability of
      intraoperative neurophysiology, though these may require a higher degree of
      neuromonitoring expertise. IOM minimizes neurological morbidity in tethered cord
      surgery.

PMID- 24013332
TI  - Syringomyelia and tethered cord in children.
AB  - INTRODUCTION: The presence of syringomyelia varies in patients with different
      forms of dysraphism; from 21 % to 67 %. Only around 60 % of patients with
      syringomyelia is likely to experience symptoms related to it. PATHOPHYSIOLOGY:
      Many theories have been outlined for the creation of syringomyelia. The one most
      applicable to tethered cord dictates that tensile radial stress may create a
      syrinx in a previously normal cord tissue and transiently lower pressure may draw
      in interstitial fluid, causing the syrinx to enlarge if fluid exit is inhibited.
      In addition, arachnoiditis increases flow resistance in the spinal subarachnoid
      space, altering temporal CSF pulse pressure dynamics, which promotes entry of CSF
      in to the spinal cord. CLINICAL PRESENTATION: There is a significant overlap
      between the symptoms that are due to tethered cord and syringomyelia, both in
      newly presenting patients with coexisting syringomyelia, and in previously
      treated patients who during follow-up present recurrent symptoms and a new
      syringomyelia cavity. TREATMENT: The treatment of patients with tethered cord and
      syringomyelia is directed towards untethering the cord from its most caudal
      region upwards and restoring spinal anatomy with reestablishment of unobstructed
      CSF flow in the subarachnoid space. Only if complete untethering has been ensured
      and syringomyelia deteriorates, then surgical treatment can be directed against
      the syrinx. In patients with spinal dysraphism and coexisting hydrocephalus,
      radiological presentation of new syringomyelia or deterioration of previously
      known syringomyelia may signify shunt obstruction "until proven otherwise".
      CONCLUSION: In most occasions, satisfactory cord untethering addresses the
      development of syringomyelia.

PMID- 24013333
TI  - Occult tethered cord syndrome: a review.
AB  - BACKGROUND: Tethered cord syndrome is a well-defined condition, the management of
      which is fairly uniform. In contrast, occult tethered cord syndrome is a recently
      defined entity, where the management is still controversial. The pathophysiology
      is unclear and may be conceptually incongruent with current understanding of
      typical tethered cord syndrome. Presentation, investigation, and management of
      this condition are reviewed, and current understanding is presented. PURPOSE: The
      aim of this study is to review the presentation, pathophysiology, investigation,
      and management of occult tethered cord syndrome. METHODS: Literature review.
      RESULTS: Patients with occult tethered cord syndrome presents predominantly with
      urologic symptoms. Adult and pediatric patients vary slightly in their
      presentation with a higher incidence of pain in the former and incontinence in
      the latter. Operative management for these patients is associated with consistent
      improvement in urologic function in particular, although surgery is also
      associated with risk of worsening symptoms. The natural history of untreated
      patients is unknown. CONCLUSIONS: As occult tethered cord syndrome becomes
      increasingly recognized, it is important to be aware of the potential benefits of
      operative intervention for appropriately selected patients. Given that the
      natural history of this entity remains unknown, a clinical trial is currently
      underway that may assist in defining the role for operative management in
      treating this condition.

PMID- 24013334
TI  - Sacrococcygeal dimple: new classification and relationship with spinal lesions.
AB  - PURPOSE: This study aims to ascertain which specific types of sacrococcygeal
      dimples are associated with underlying spinal cord malformations. METHODS: From
      2008 to 2011, we prospectively examined children less than 2 years old with
      sacrococcygeal dimples. Each patient underwent clinical assessment of dimples and
      magnetic resonance imaging. We devised the following new classification of
      dimples according to their location: type 1, dimples located within the gluteal
      crease, including coccygeal pits; type 2, dimples located at the upper edge of
      the gluteal crease with associated curving or deformity of that crease; and type
      3, dimples located well above the gluteal crease. RESULTS: We evaluated 142
      patients with sacrococcygeal dimples. Although we identified spinal malformations
      such as spinal lipomas, filum cysts, and thickened fila terminalia in only 17 %
      of infants with type 1 dimples, we observed them in 45 % with type 2 and 55 %
      with type 3. Thus, in terms of the rate of spinal malformations, there are
      significant differences between types 1 and 2 and between types 1 and 3.
      CONCLUSIONS: We propose a new classification of sacrococcygeal dimples. Although
      type 2 dimples have previously been classified as simple dimples that require no
      further investigation, we have identified that they are strongly associated with
      spinal deformities, comparable to atypical type 3 dimples. Thus, both types 2 and
      3 dimples warrant radiological investigation.

PMID- 24013335
TI  - Spinal inclusion cysts.
AB  - BACKGROUND: Dermoid and epidermoid tumours are related though pathologically
      distinct entities that can be combined under the term inclusion cysts. Most are
      of developmental origin and in the spine may be intramedullary, intradural
      extramedullary or extraspinal in location. The terminology, aetiology, radiology
      and optimal management of spinal inclusion cysts have been the source of ongoing
      controversy. AIMS: A retrospective review of surgical cases from a single
      institution has been conducted, and this experience is discussed in the context
      of the existing literature. RESULTS: Sixteen cases of paediatric spinal inclusion
      cysts were treated between 2002 and 2012. Associated anomalies included dermal
      sinus track (11), previous myelomeningocele (4) and Currarino syndrome (1). The
      lesions spanned 1-8 spinal levels; in half the cases, there was a history of
      secondary infection at the time of presentation. The aim of treatment was
      complete excision, and macroscopic removal was achieved in all cases. The most
      significant adverse outcome was related to sphincter dysfunction, and this was
      observed in four cases, two with a prior history of myelomeningocele and two who
      had presented with active infection. No instances of recurrence were recorded
      during a median follow up of 7.4 years (range 1-11 years). CONCLUSIONS: Spinal
      inclusion cysts are aetiologically diverse lesions, though in paediatric
      practice, most occur in association with a dysraphic anomaly. There are no
      consistent clinical or radiological features that will reliably distinguish
      between dermoid and epidermoid, and both may result in symptoms from mass effect
      or infection. The recurrence rate is low if complete macroscopic resection can be
      achieved.

PMID- 24013336
TI  - Occult spinal dysraphism: lessons learned by retrospective analysis of 149
      surgical cases about natural history, surgical indications, urodynamic testing,
      and intraoperative neurophysiological monitoring.
AB  - PURPOSE: Prophylactic surgery is indicated for lipoma of the filum, while it is
      still debated for the conus lipomas and more complex tethering malformations of
      the cord. METHODS: We retrospectively reviewed the preoperative and postoperative
      clinical histories and long-term outcomes of 149 operated patients (33 adults,
      116 children). Intraoperative neurophysiological monitoring (NPM) was utilized
      since 1998. Their malformative lesions were reclassified following recent Pang's
      embryological criteria for surgical complexity. In nine cases, the spinal
      tethering malformation was associated with an anorectal malformation (ARM) and in
      nine with a Chiari I malformation (CM1). RESULTS: One hundred nineteen (80 %)
      patients were symptomatic at the time of surgery, 66 (44 %) having presented with
      progressive preoperative deterioration. Postoperative surgery-related
      deterioration was observed in 6 % of the cases operated on under the
      intraoperative NPM control. Surgery did not improve any deficit, especially of
      sphincter functions, independently from the type of associated malformation (ARM,
      CM1). Urodynamic testing was a reliable predictor both in the preoperative and in
      the follow-up period of subsequent neurological deterioration. In the long-term
      follow-up, an increasing percentage of retethering was observed, especially
      concerning complex cases submitted to partial excision. The surgical risk
      increased with repeated operations. CONCLUSIONS: This study demonstrates that the
      rate of the natural deterioration associated with a conservative approach is
      higher than in patients operated on prophylactically, if the operation is
      performed by a team with a special expertise. However, the first surgical
      procedure should be aimed at detethering the conus completely, with the aid of
      intraoperative NPM; even in expert hands, it is associated with a high risk of
      clinical deterioration. Based on these results, we are increasing the percentage
      of children to whom surgery is offered when still asymptomatic as well as the
      degree of the lipoma excision to prevent retethering. However, in cases of
      rethetering and subjects presenting in adult age, we suggest to consider for
      surgery only those symptomatic. Urodynamic testing and magnetic resonance imaging
      in prone position were, in our experience, the best tools for screening those
      patients at risk of symptomatic retethering.

PMID- 24013337
TI  - Health-related quality of life in children and adolescents with spinal
      dysraphism: results from a Taiwanese sample.
AB  - PURPOSE: This study was designed to investigate health-related quality of life
      (HRQL) in children and adolescents with spinal dysraphism and to determine the
      differences between the myelomeningocele (MMC) and lipomyelomeningocele (LMMC)
      groups. METHODS: Thirty-two patients (mean age, 13.2 years) with MMC and 28
      patients (mean age, 11.3 years) with LMMC participated in this study. HRQL was
      measured using the Child Health Questionnaire-Parent Form 50 (CHQ-PF50). The CHQ
      PF50 scores for the study participants were compared with those of a reference
      sample of healthy Taiwanese children. Outcomes for children with MMC were
      compared with those for children with LMMC. We also explored the relationships of
      the lesion level and associated medical problems with HRQL in these subjects.
      RESULTS: Patients with MMC had significantly lower scores on the physical and
      psychosocial aspects of CHQ-PF50 than did healthy children. Patients with LMMC
      had lower scores on some domains but had comparable psychosocial summary scores.
      Significant differences were noted between the MMC and LMMC groups for all
      subscales and both summary scores. Children with a higher lesion level had poor
      physical health (r = -0.52, P < 0.001) but not poor psychosocial health. The
      number of associated medical problems, indicating their severity, was related to
      both physical (r = -0.77, P < 0.001) and psychosocial health (r = -0.57, P <
      0.001). CONCLUSIONS: Children and adolescents with MMC have reduced HRQL compared
      with those with LMMC. Children and adolescents with more associated medical
      problems have the greatest risk of diminished physical and psychosocial well
      being.

PMID- 24013339
TI  - Abstracts of the 41st Annual Meeting of the International Society for Pediatric
      Neurosurgery, Sept 29-Oct 3, 2013, Mainz, Germany.

PMID- 24013338
TI  - Raimondi award.

PMID- 24013340
TI  - Entomopathogenic marine actinomycetes as potential and low-cost biocontrol agents
      against bloodsucking arthropods.
AB  - A novel approach to control strategies for integrated blood-feeding parasite
      management is in high demand, including the use of biological control agents. The
      present study aims to determine the efficacy of optimized crude extract of
      actinomycetes strain LK1 as biological control agent against the fourth-instar
      larvae of Anopheles stephensi and Culex tritaeniorhynchus (Diptera: Culicidae)
      and adults of Haemaphysalis bispinosa, Rhipicephalus (Boophilus) microplus
      (Acari: Ixodidae), and Hippobosca maculata (Diptera: Hippoboscidae).
      Antiparasitic activity was optimized using the Plackett-Burman method, and the
      design was developed using the software Design-Expert version 8.0.7.1. The
      production of the optimized crude actinomycetes LK1 strain extract was performed
      using response surface methodology to optimize the process parameters of protease
      inhibitor activity of marine actinobacteria for the independent variables like
      pH, temperature, glucose, casein, and NaCl at two levels (-1 and +1). The
      potential actinomycetes strain was identified as Saccharomonas spp., and the
      metamodeling surface simulation procedure was followed. It was studied using a
      computer-generated experimental design, automatic control of simulation
      experiments, and sequential optimization of the metamodels fitted to a simulation
      response surface function. The central composite design (CCD) used for the
      analysis of treatment showed that a second-order polynomial regression model was
      in good agreement with the experimental results at R (2) = 0.9829 (p < 0.05). The
      optimized values of the variables for antioxidant production were pH 6.00,
      glucose 1.3%, casein 0.09%, temperature 31.23  degrees C, and NaCl 0.10%. The LK1
      strain-optimized crude extract was purified using reversed-phase high-pressure
      liquid chromatography, and the isolated protease inhibitor showed antiparasitic
      activity. The antiparasitic activity of optimized crude extract of LK1 was tested
      against larvae of A. stephensi (LC50 = 31.82 ppm; r(2) = 0.818) and C.
      tritaeniorhynchus (LC50 = 26.62 ppm; r(2) = 0.790) and adults of H. bispinosa
      (LC50 = 106.58 ppm; r(2) = 0.871), R. (B.) microplus (LC50 = 92.96 ppm; r(2) =
      0.913), and H. maculata (LC50 = 84.90 ppm; r(2) = 0.857).

PMID- 24013341
TI  - Approaches to genotyping individual miracidia of Schistosoma japonicum.
AB  - Molecular genetic tools are needed to address questions as to the source and
      dynamics of transmission of the human blood fluke Schistosoma japonicum in
      regions where human infections have reemerged, and to characterize
      infrapopulations in individual hosts. The life stage that interests us as a
      target for collecting genotypic data is the miracidium, a very small larval stage
      that consequently yields very little DNA for analysis. Here, we report the
      successful development of a multiplex format permitting genotyping of 17
      microsatellite loci in four sequential multiplex reactions using a single
      miracidium held on a Whatman Classic FTA indicating card. This approach was
      successful after short storage periods, but after long storage (>4 years),
      considerable difficulty was encountered in multiplex genotyping, necessitating
      the use of whole genome amplification (WGA) methods. WGA applied to cards stored
      for long periods of time resulted in sufficient DNA for accurate and repeatable
      genotyping. Trials and tests of these methods, as well as application to some
      field-collected samples, are reported, along with the discussion of the potential
      insights to be gained from such techniques. These include recognition of sibships
      among miracidia from a single host, and inference of the minimum number of worm
      pairs that might be present in a host. 

PMID- 24013342
TI  - In vivo anthelmintic effect of flavonol rhamnosides from Dryopteris crassirhizoma
      against Dactylogyrus intermedius in goldfish (Carassius auratus).
AB  - The purpose of the present study was to assess the anthelmintic property of plant
      derived polyphenolic compounds extracted and isolated from Dryopteris
      crassirhizoma against Dactylogyrus intermedius in goldfish. The active ethyl
      acetate extract was loaded on an open silica gel column and eluted with
      chloroform-methanol. According to (1)H-nuclear magnetic resonance (NMR), (13)C
      NMR, and mass spectral data, the structures of three purified compounds were
      identified as protocatechuic acid, sutchuenoside A, and kaempferitrin. Among
      these compounds, sutchuenoside A and kaempferitrin were observed to be effective
      with median effective concentration (EC50) of 3.01 and 2.71 mg L(-1),
      respectively. The alterations in the tegument of the parasites treated with
      isolated compound were examined using scanning electron microscopes.
      Ultrastructural micrographs revealed shrinkage of body surface, dense tegumental
      folds, and disheveled protuberances. The structural deformities in the treated
      parasites were indicative of an efficient anthelmintic activity of the isolated
      compound kaempferitrin. In addition, the 48-h median lethal concentration for
      sutchuenoside A and kaempferitrin against goldfish were 12.03- and 11.98-fold
      higher than corresponding EC50. The present results showed that ethyl acetate
      extract of D. crassirhizoma may be considered as a potent source, and
      sutchuenoside A and kaempferitrin as new natural parasitic agents against D.
      intermedius. 

PMID- 24013343
TI  - Eco-friendly microbial route to synthesize cobalt nanoparticles using Bacillus
      thuringiensis against malaria and dengue vectors.
AB  - The developments of resistance and persistence to chemical insecticides and
      concerns about the non-target effects have prompted the development of eco
      friendly mosquito control agents. The aim of this study was to investigate the
      larvicidal activities of synthesized cobalt nanoparticles (Co NPs) using bio
      control agent, Bacillus thuringiensis against malaria vector, Anopheles subpictus
      and dengue vector, Aedes aegypti (Diptera: Culicidae). The synthesized Co NPs
      were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR),
      Field-emission scanning electron microscopy (FESEM) with energy dispersive X-ray
      spectroscopy, and Transmission electron microscopy (TEM). XRD analysis showed
      three distinct diffraction peaks at 27.03 degrees , 31.00 degrees , and 45.58
      degrees  indexed to the planes 102, 122, and 024, respectively on the face
      centered cubic cobalt acetate with an average size of 85.3 nm. FTIR spectra
      implicated role of the peak at 3,436 cm(-1) for O-H hydroxyl group, 2924 cm(-1)
      for methylene C-H stretch in the formation of Co NPs. FESEM analysis showed the
      topological and morphological appearance of NPs which were found to be spherical
      and oval in shape. TEM analysis showed polydispersed and clustered NPs with an
      average size of 84.81 nm. The maximum larvicidal mortality was observed in the
      cobalt acetate solution, B. thuringiensis formulation, and synthesized Co NPs
      against fourth instar larvae of A. subpictus and A. aegypti with LC50 values of
      29.16, 8.12, 3.59 mg/L; 34.61, 6.94, and 2.87 mg/L; r (2) values of 0.986, 0.933,
      0.942; 0.962, 0.957, and 0.922, respectively. 

PMID- 24013344
TI  - Sequencing the complete mitochondrial genome of Eimeria mitis strain USDA 50
      (Apicomplexa: Eimeriidae) suggests conserved start positions for mtCOI- and
      mtCOIII-coding regions.
AB  - Four complete mitochondrial (mt) sequences from a single-oocyst-derived line of
      Eimeria mitis USDA 50 were obtained (three from cloned whole-genome PCR products,
      one from directly sequenced whole-genome PCR product). The mt genome is 6,408 bp
      long with three genes (CytB, cytochrome c oxidase subunit I (COI) and cytochrome
      c oxidase subunit III (COIII)) and many rDNA fragments (large subunit rDNA 13,
      small subunit rDNA 10); organisation was identical to other Eimeria sp. mt
      genomes. Conserved start codon positions for both COI and COIII are suggested for
      all Eimeria mt genomes; these start codon positions exist and may also be
      conserved, in related apicomplexan parasites. Within the three separate cloned
      PCR products of near-complete mt genomes, there were 26 nucleotide differences
      (collectively) compared to the directly sequenced mt genome. These changes appear
      to be base misincorporations during PCR. Direct sequencing of long PCR
      amplification products may be more likely to generate accurate mt genomic
      sequences than cloning and subsequent sequencing. 

PMID- 24013345
TI  - Characterization of export receptor exportins (XPOs) in the parasite Schistosoma
      mansoni.
AB  - Several proteins and different species of RNA that are produced in the nucleus
      are exported through the nuclear pore complexes, which require a family of
      conserved nuclear export receptors called exportins (XPOs). It has been reported
      that the XPOs (XPO1, XPO5, and XPOT) are directly involved in the transport
      processes of noncoding RNAs from the nucleus to the cytoplasm and/or from
      cytoplasm to the nucleus. All three genes are present in fungi, plants, and
      deuterostome metazoans. However, protostome metazoan species lack one of the
      three genes across evolution. In this report, we have demonstrated that all three
      XPO proteins are present in the parasite protostome Schistosoma mansoni. As this
      parasite has a complex life cycle presenting several stages in different hosts
      and environments, implying a differential gene regulation, we proposed a genomic
      analysis of XPOs to validate their annotation. The results showed the
      conservation of exportin family members and gene duplication events in S.
      mansoni. We performed quantitative RT-PCR, which revealed an upregulation of
      SmXPO1 in 24 h schistosomula (sixfold when compared with cercariae), and similar
      transcription levels were observed for SmXPO5 and SmXPOT in all the analyzed
      stages. These three XPO proteins have been identified for the first time in the
      protostome clade, which suggests a higher complexity in RNA transport in the
      parasite S. mansoni. Taken together, these results suggest that RNA transport by
      exportins might control cellular processes during cercariae, schistosomula, and
      adult worm development. 

PMID- 24013346
TI  - Exertional heat stroke management strategies in United States high school
      football.
AB  - BACKGROUND: The 5-year period of 2005-2009 saw more exertional heat stroke
      related deaths in organized sports than any other 5-year period in the past 35
      years. The risk of exertional heat stroke appears highest in football,
      particularly during the preseason. PURPOSE: To estimate the incidence of
      exertional heat stroke events and assess the utilization of exertional heat
      stroke management strategies during the 2011 preseason in United States high
      school football programs. STUDY DESIGN: Cross-sectional study; Level of evidence,
      3. METHODS: A self-administered online questionnaire addressing the incidence of
      exertional heat stroke events and utilization of exertional heat stroke
      management strategies (eg, removing athlete's football equipment, calling
      Emergency Medical Services [EMS]) was completed in May to June 2012 by 1142
      (18.0%) athletic trainers providing care to high school football athletes during
      the 2011 preseason. RESULTS: Among all respondents, 20.3% reported treating at
      least 1 exertional heat stroke event. An average of 0.50 +/- 1.37 preseason
      exertional heat stroke events were treated per program. Athletic trainers
      responding to exertional heat stroke reported using an average of 6.6 +/- 1.8
      management strategies. The most common management strategies were low-level
      therapeutic interventions such as removing the athlete's football equipment
      (98.2%) and clothing (77.8%) and moving the athlete to a shaded area (91.6%). Few
      athletic trainers reported active management strategies such as calling EMS
      (29.3%) or using a rectal thermometer to check core body temperature (0.9%).
      Athletic trainers in states with mandated preseason heat acclimatization
      guidelines reported a higher utilization of management strategies such as cooling
      the athlete through air conditioning (90.1% vs 65.0%, respectively; P < .001),
      immersion in ice water (63.0% vs 45.4%, respectively; P = .01), or fans (54.3% vs
      42.0%, respectively; P = .06) and monitoring the athlete's temperature (60.5% vs
      46.2%, respectively; P = .04). CONCLUSION: Preseason exertional heat stroke
      events, which are likely to be fatal if untreated, were reported by one fifth of
      all athletic trainers in high school football programs. The standard of care is
      (and should be) to treat proactively; therefore, treatment is not a perfect proxy
      for incidence. Nevertheless, there is an urgent need for improved education and
      awareness of exertional heat stroke in high school football. Areas of improvement
      include the greatly increased use of rectal thermometers and immersion in ice
      water.

PMID- 24013347
TI  - Stable surgical repair with accelerated rehabilitation versus nonsurgical
      treatment for acute Achilles tendon ruptures: a randomized controlled study.
AB  - BACKGROUND: The optimal treatment for acute Achilles tendon ruptures is still a
      subject of debate. Early loading of the tendon is a factor that has been shown to
      be beneficial to recovery and to minimize complications. The main outcome of
      previous studies has been complications such as reruptures and deep infections,
      without focusing on the functional outcome relevant to the majority of patients
      who do not experience these complications. PURPOSE: To evaluate whether stable
      surgical repair and early loading of the tendon could improve patient-reported
      outcome and function after an acute Achilles tendon rupture. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: A total of 100
      patients (86 men, 14 women; mean age, 40 years) with an acute total Achilles
      tendon rupture were randomized to either surgical treatment, including an
      accelerated rehabilitation protocol, or nonsurgical treatment. The primary
      outcome was the Achilles tendon Total Rupture Score (ATRS). The patients were
      evaluated at 3, 6, and 12 months for symptoms, physical activity level, and
      function. RESULTS: There were no significant differences between the groups in
      terms of symptoms, physical activity level, or quality of life. There was a trend
      toward improved function in surgically treated patients; the results were
      significantly superior when assessed by the drop countermovement jump (95% CI,
      0.03-0.15; P = .003) and hopping (95% CI, 0.01-0.33; P = .040). No reruptures
      occurred in the surgical group, while there were 5 in the nonsurgical group (P =
      .06). There were 6 superficial infections in the surgically treated group;
      however, these superficial infections had no bearing on the final outcome.
      Symptoms, reduced quality of life, and functional deficits still existed 12
      months after injury on the injured side in both groups. CONCLUSION: The results
      of the present study demonstrate that stable surgical repair with accelerated
      tendon loading could be performed in all (n = 49) patients without reruptures and
      major soft tissue-related complications. However, this treatment was not
      significantly superior to nonsurgical treatment in terms of functional results,
      physical activity, or quality of life.

PMID- 24013348
TI  - Biomechanical evaluation of different suture techniques for arthroscopic
      transtibial pull-out repair of posterior medial meniscus root tears.
AB  - BACKGROUND: A tear of the posterior medial meniscus root (PMMR) is increasingly
      recognized as a serious knee joint injury. Several suture techniques for
      arthroscopic transtibial pull-out repair have been described; however, only
      limited data about the biomechanical properties of these techniques are currently
      available. HYPOTHESIS: There are significant differences between the tested
      suture techniques, with more complex suture configurations providing superior
      biomechanical properties. STUDY DESIGN: Controlled laboratory study. METHODS: A
      total of 40 porcine medial menisci were randomly assigned to 1 of 4 groups (10
      specimens each) according to suture technique: two simple stitches (TSS),
      horizontal mattress suture (HMS), modified Mason-Allen suture (MMA), and two
      modified loop stitches (TLS). Meniscus-suture constructs were subjected to cyclic
      loading followed by load-to-failure testing in a servohydraulic material testing
      machine. RESULTS: During cyclic loading, the HMS and TLS groups showed a
      significantly higher displacement after 100, 500, and 1000 cycles compared with
      the TSS and MMA groups. After 1000 cycles, the highest displacement was found for
      the TLS group, with significant differences compared with all other groups.
      During load-to-failure testing, the highest maximum load and yield load were
      observed for the MMA group, with statistically significant differences compared
      with the TSS and TLS groups. With regard to stiffness, the TSS and MMA groups
      showed significantly higher values compared with the HMS and TLS groups.
      CONCLUSION: The MMA technique provided the best biomechanical properties with
      regard to cyclic loading and load-to-failure testing. The TSS technique seems to
      be a valuable alternative. Both the HMS and TLS techniques have the disadvantage
      of lower stiffness and higher displacement during cyclic loading. CLINICAL
      RELEVANCE: Using a MMA technique may improve healing rates and avoid progressive
      extrusion of the medial meniscus after transtibial pull-out repair of PMMR tears.
      The TSS technique may be used as an alternative that is easier to perform, but a
      more careful rehabilitation program is possibly necessary to avoid early failure.

PMID- 24013349
TI  - Heritability and inter-population differences in lipid profiles of Drosophila
      melanogaster.
AB  - Characterizing and understanding the complex spectrum of lipids in higher
      organisms lags far behind our analysis of genome and transcriptome sequences.
      Here we generate and evaluate comprehensive lipid profiles (>200 lipids) of 92
      inbred lines from five different Drosophila melanogaster populations. We find
      that the majority of lipid species are highly heritable, and even lipids with odd
      chain fatty acids, which cannot be generated by the fly itself, also have high
      heritabilities. Abundance of the endosymbiont Wolbachia, a potential provider of
      odd-chained lipids, was positively correlated with this group of lipids.
      Additionally, we show that despite years of laboratory rearing on the same
      medium, the lipid profiles of the five geographic populations are sufficiently
      distinct for population discrimination. Our data predicts a strikingly different
      membrane fluidity for flies from the Netherlands, which is supported by their
      increased ethanol tolerance. We find that 18% of lipids show strong concentration
      differences between males and females. Through an analysis of the correlation
      structure of the lipid classes, we find modules of co-regulated lipids and begin
      to associate these with metabolic constraints. Our data provide a foundation for
      developing associations between variation in lipid composition with variation in
      other metabolic attributes, with genome-wide variation, and with metrics of
      health and overall reproductive fitness. 

PMID- 24013351
TI  - It is time for a harmonized ethical review procedure across Europe.

PMID- 24013352
TI  - DNA-directed self-assembly of shape-controlled hydrogels.
AB  - Using DNA as programmable, sequence-specific 'glues', shape-controlled hydrogel
      units are self-assembled into prescribed structures. Here we report that
      aggregates are produced using hydrogel cubes with edge lengths ranging from 30
      MUm to 1 mm, demonstrating assembly across scales. In a simple one-pot agitation
      reaction, 25 dimers are constructed in parallel from 50 distinct hydrogel cube
      species, demonstrating highly multiplexed assembly. Using hydrogel cuboids
      displaying face-specific DNA glues, diverse structures are achieved in aqueous
      and in interfacial agitation systems. These include dimers, extended chains and
      open network structures in an aqueous system, and dimers, chains of fixed length,
      T-junctions and square shapes in the interfacial system, demonstrating the
      versatility of the assembly system.

PMID- 24013354
TI  - A mildly painful wrist mass.

PMID- 24013356
TI  - Fluorescence turn-on detection of a protein using cytochrome c as a quencher.
AB  - A new approach for the sensitive and selective sensing of a protein has been
      developed. Cytochrome c could quench the fluorescence of a fluorophore labeled
      aptamer efficiently. The specific binding between the aptamer and the target
      protein resulted in a turn-on emission signal, which could be used for protein
      quantification. 

PMID- 24013355
TI  - Novel insights in genetic transformation of the probiotic yeast Saccharomyces
      boulardii.
AB  - Saccharomyces boulardii (S. boulardii) is a probiotic yeast related to
      Saccharomyces cerevisiae (S. cerevisiae) but with distinct genetic, taxonomic and
      metabolic properties. S. cerevisiae has been used extensively in biotechnological
      applications. Currently, many strains are available, and multiple genetic tools
      have been developed, which allow the expression of several exogenous proteins of
      interest with applications in the fields of medicine, biofuels, the food
      industry, and scientific research, among others. Although S. boulardii has been
      widely studied due to its probiotic properties against several gastrointestinal
      tract disorders, very few studies addressed the use of this yeast as a vector for
      expression of foreign genes of interest with biotechnological applications. Here
      we show that, despite the similarity of the two yeasts, not all genetic tools
      used in S. cerevisiae can be applied in S. boulardii. While transformation of the
      latter could be obtained using a commercial kit developed for the former,
      consequent screening of successful transformants had to be optimized. We also
      show that several genes frequently used in genetic manipulation of S. cerevisiae
      (e.g., promoters and resistance markers) are present in S. boulardii. Sequencing
      revealed a high rate of homology (> 96%) between the orthologs of the two yeasts.
      However, we also observed some of them are not eligible to be targeted for
      transformation of S. boulardii. This work has important applications toward the
      potential of this probiotic yeast as an expression system for genes of interest. 

PMID- 24013357
TI  - Phosphorylation status of 72 kDa MMP-2 determines its structure and activity in
      response to peroxynitrite.
AB  - Matrix metalloproteinase-2 (MMP-2) is a key intra- and extra-cellular protease
      which contributes to several oxidative stress related pathologies. A molecular
      understanding of 72 kDa MMP-2 activity, directly mediated by S-glutathiolation of
      its cysteine residues in the presence of peroxynitrite (ONOO(-)) and by
      phosphorylation of its serine and threonine residues, is essential to develop new
      generation inhibitors of intracellular MMP-2. Within its propeptide and collagen
      binding domains there is an interesting juxtaposition of predicted
      phosphorylation sites with nearby cysteine residues which form disulfide bonds.
      However, the combined effect of these two post-translational modifications on MMP
      2 activity has not been studied. The activity of human recombinant 72 kDa MMP-2
      (hrMMP-2) following in vitro treatments was measured by troponin I proteolysis
      assay and a kinetic activity assay using a fluorogenic peptide substrate. ONOO(-)
      treatment in the presence of 30 uM glutathione resulted in concentration
      dependent changes in MMP-2 activity, with 0.1-1 uM increasing up to twofold and
      100 uM attenuating its activity. Dephosphorylation of MMP-2 with alkaline
      phosphatase markedly increased its activity by sevenfold, either with or without
      ONOO(-). Dephosphorylation of MMP-2 also affected the conformational structure of
      the enzyme as revealed by circular dichroism studies, suggesting an increase in
      the proportion of alpha-helices and a decrease in beta-strands compared to the
      phosphorylated form of MMP-2. These results suggest that ONOO(-) activation (at
      low uM) and inactivation (at high uM) of 72 kDa MMP-2, in the presence or absence
      of glutathione, is also influenced by its phosphorylation status. These insights
      into the role of post-translational modifications in the structure and activity
      of 72 kDa MMP-2 will aid in the development of inhibitors specifically targeting
      intracellular MMP-2. 

PMID- 24013358
TI  - Fast spectral coherent anti-Stokes Raman scattering microscopy with high-speed
      tunable picosecond laser.
AB  - We develop a coherent anti-Stokes Raman scattering (CARS) microscopy system
      equipped with a tunable picosecond laser for high-speed wavelength scanning. An
      acousto-optic tunable filter (AOTF) is integrated in the laser cavity to enable
      wavelength scanning by varying the radio frequency waves applied to the AOTF
      crystal. An end mirror attached on a piezoelectric actuator and a pair of
      parallel plates driven by galvanometer motors are also introduced into the cavity
      to compensate for changes in the cavity length during wavelength scanning to
      allow synchronization with another picosecond laser. We demonstrate fast spectral
      imaging of 3T3-L1 adipocytes every 5  cm-1 in the Raman spectral region around
      2850  cm-1 with an image acquisition time of 120 ms. We also demonstrate fast
      switching of Raman shifts between 2100 and 2850  cm-1, corresponding to CD2
      symmetric stretching and CH2 symmetric stretching vibrations, respectively. The
      fast-switching CARS images reveal different locations of recrystallized
      deuterated and nondeuterated stearic acid.

PMID- 24013359
TI  - Exploring associations of 6-thioguanine nucleotide levels and other predictive
      factors with therapeutic response to azathioprine in pediatric patients with IBD
      using multilevel analysis.
AB  - BACKGROUND: Metabolite monitoring and response predictors to azathioprine (AZA)
      in pediatric inflammatory bowel disease (IBD) are debatable. In an attempt to
      optimize thiopurine therapy and understand the mechanism of action of
      thiopurines, we correlated metabolites and other factors with AZA efficacy in
      children with IBD. METHODS: Data from 86 children with IBD with 440 metabolite
      measurements were retrospectively analyzed using multilevel logistic regression
      analyses. A therapeutic response was defined as a pediatric Crohn's disease
      activity index <=10 for Crohn's disease or a pediatric ulcerative colitis
      activity index <=10 for ulcerative colitis without any treatment with steroids,
      antitumor necrosis factor, other immunomodulators, or exclusive enteral
      nutrition. RESULTS: The 6-thioguanine nucleotide levels >250 pmol per 8 * 10 red
      blood cells correlated with a higher response (odds ratio, 4.14; 95% confidence
      interval, 1.49-11.46, P = 0.007), whereas 6-methyl-mercaptopurine and 6-methyl
      mercaptopurine:6-thioguanine nucleotide ratio showed no correlation. Other novel
      response predictors in children with IBD were relative leukopenia (odds ratio,
      14.01; 95% confidence interval, 3.77-52.10; P < 0.001) and the absence of
      lymphopenia (odds ratio, 3.71; 95% confidence interval, 1.26-10.89; P = 0.017).
      Lower thiopurine methyltransferase activity (P = 0.015), lower platelet count (P
      = 0.020), and higher aspartate aminotransferase level (P = 0.009) also predicted
      therapeutic response. Age, gender, patient adherence, the duration of AZA
      therapy, IBD type, erythrocyte count, and erythrocyte sedimentation rate did not
      predict efficacy. The high interindividual variability accounting for 57.7% of
      variance in therapeutic response was observed. CONCLUSIONS: The significant 6
      thioguanine nucleotide level-response relationship may support metabolite
      monitoring to improve thiopurine efficacy in pediatric IBD. The reported response
      predictors may be helpful for treatment optimization in AZA-treated children with
      IBD, but should be proved in prospective studies.

PMID- 24013360
TI  - A new heterotopic transplant animal model of intestinal fibrosis.
AB  - BACKGROUND: Severe mucosal tissue damage requiring efficient wound healing is a
      main feature of inflammatory bowel disease but excessive tissue repair promotes
      fibrosis. The clinical investigation of fibrosis is confined to the limited
      amount of biological material available from patients. This makes the
      establishment of a new animal model, a highly desirable goal. We investigated
      whether intestinal fibrosis occurs after heterotopic transplantation of small
      bowel resections in rats. METHODS: Donor (Brown Norway or Lewis rats) small bowel
      resections were transplanted subcutaneously into the neck of recipients (Lewis
      rats). Grafts were explanted 2, 7, 14, and 21 days after transplantation.
      RESULTS: Heterotopic intestinal transplants remained viable for 21 days. Rapid
      loss of crypt structures at day 2 after intestinal transplantation was followed
      by lymphocyte infiltration and obliteration of the intestinal lumen by fibrous
      tissue at day 21. Loss of the intestinal epithelium was confirmed by the lack of
      cytokeratin staining in immunohistochemistry. Collagen expression was increased
      with time after transplantation as confirmed by real-time PCRs, Elastica van
      Gieson, and Sirius Red staining. Lumen obliteration was connected with increased
      expression of potent mediators of fibrosis such as alpha5beta6 integrin,
      interleukin (IL)-13, and transforming growth factor beta. Myofibroblast phenotype
      was demonstrated by the presence of both alpha-smooth muscle actin and vimentin
      in the obliterated lumen. CONCLUSIONS: We established a method for heterotopic
      transplantation of small bowel resections. A variety of histologic and molecular
      features of fibrosis were observed in the heterotopic intestinal grafts which
      suggests, that this new in vivo model will be instrumental in studying
      pathogenesis and treatment of intestinal fibrosis.

PMID- 24013361
TI  - Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory
      bowel disease: a prospective study.
AB  - BACKGROUND: Data on the value of therapeutic drug monitoring of infliximab (IFX)
      to predict mucosal healing (MH) in inflammatory bowel diseases (IBD) are scarce.
      METHODS: All consecutive patients with IBD receiving ongoing IFX (5 mg/kg)
      treatment and developing secondary failure to IFX were enrolled in a prospective
      study between June 2010 and May 2011. IFX trough levels, antibodies to IFX
      concentrations, C-reactive protein levels, and fecal calprotectin were measured
      before IFX optimization and at week 8. A proctosigmoidoscopy was performed on the
      day of first IFX optimization and at week 8 in all patients with ulcerative
      colitis (UC). MH was defined by fecal calprotectin <250 MUg/g stools in Crohn's
      disease (CD) and by an endoscopic Mayo score of 0 or 1 in UC. RESULTS: This study
      included 52 patients with IBD: 34 patients with CD (mean Crohn's Disease Activity
      Index, 300; mean C-reactive protein, 28 +/- 10 mg/L; mean fecal calprotectin, 705
      +/- 300 MUg/g) and 18 patients with UC (mean Simple Clinical Colitis Activity
      Index, 7; mean Mayo endoscopic score, 3). After IFX dose intensification, half of
      CD and UC patients achieved MH. Increase in IFX trough levels (called "delta IFX"
      in micrograms per milliliter) was associated with MH in both CD and UC (P =
      0.001). A delta IFX >0.5 MUg/mL was associated with MH (sensitivity [se], 0.88;
      specificity [sp], 0.77; P = 0.0001, area under the receiver operating
      characteristic curve, 0.89). On multivariate analysis, the only factor associated
      with MH after IFX optimization was a delta IFX >0.5 ug/mL (likelihood ratio =
      2.02; 95% confidence interval, 1.01-4.08; P = 0.048) in patients with IBD.
      CONCLUSIONS: Therapeutic drug monitoring of IFX strongly predicts the likelihood
      of achieving MH following IFX dose intensification in both CD and UC.

PMID- 24013362
TI  - DNA-PKcs inhibition sensitizes cancer cells to carbon-ion irradiation via
      telomere capping disruption.
AB  - Heavy-ion irradiation induces a higher frequency of DNA double strand breaks
      (DSBs) which must be properly repaired. Critical shortening of telomeres can
      trigger DNA damage responses such as DSBs. Telomeres are very sensitive to
      oxidative stress such as ionizing radiation. The DNA-dependent protein kinase
      catalytic subunit (DNA-PKcs) is the central component in the non-homologous end
      joining (NHEJ) repair complex and participates in telomere maintenance.
      Therefore, it is expected to enhance the cell killing effect of heavy-ion
      irradiation via DNA-PKcs inhibition. To test this hypothesis, cellular
      radiosensitivity was measured by the clonal genetic assay. DNA damage repair was
      relatively quantified by long PCR. Apoptosis was quantified by flow-cytometric
      analysis of annexin V/PI double staining, and senescence was analyzed by
      galactosidase activity. Telomere length was semi-quantified by real-time PCR. P53
      and p21 expression was determined by western blotting. Our data demonstrated that
      MCF-7 and HeLa cells with DNA-PKcs inhibition were more susceptible to carbon-ion
      irradiation than Those without DNA-PKcs inhibition. Even though NHEJ was
      inhibited by the DNA-PKcs specific inhibitor, NU7026, most DNA damage induced by
      carbon-ion irradiation was repaired within 24 hours after irradiation in both
      cell lines. However, potential lethal damage repair (PLDR) could not restore
      cellular inactivation in DNA-PKcs inhibited cells. MCF-7 cells showed extensive
      senescence and accelerated telomere length reduction, while HeLa cells underwent
      significant apoptosis after irradiation with NU7026 incubation. In addition, both
      cell lines with shorter telomere were more susceptible to carbon-ion radiation.
      Our current data suggested that DNA-PKcs inhibition could enhance cellular
      sensitivity to carbon-ion radiation via disturbing its functional role in
      telomere end protection. The combination of DNA-PKcs inhibition and carbon-ion
      irradiation may be an efficient method of heavy-ion therapy. 

PMID- 24013363
TI  - Chemometric Resolution and Quantification of Four-Way Data Arising from
      Comprehensive 2D-LC-DAD Analysis of Human Urine.
AB  - Two-dimensional liquid chromatography (LC*LC) is quickly becoming an important
      technique for the analysis of complex samples, owing largely to the relatively
      high peak capacities attainable by this analytical technique. With the increase
      in the complexity of the sample comes a corresponding increase in the complexity
      of the collected data. Thus the need for chemometric methods capable of resolving
      and quantifying such data is ever more urgent in order to obtain the maximum
      information available from the data. To this end, we have developed a chemometric
      method that combines iterative key set factor analysis and multivariate curve
      resolution-alternating least squares analysis with a spectral selectivity
      constraint that is shown to be capable of resolving chromatographically rank
      deficient, non-multilinear data. (Spectrally rank deficient compounds can only be
      quantified if the peaks having the same spectra are chromatographically
      resolved.) Over 50 chromatographic peaks were found in a relatively small section
      of a LC*LC-diode array data set of replicate urine samples (a four-way data set)
      using the developed method. The relative concentrations for 34 of the 50 peaks
      were determined with % RSD values ranging from 0.09 % to 16 %.

PMID- 24013364
TI  - Comparative genomics of the Mycobacterium signaling architecture and implications
      for a novel live attenuated Tuberculosis vaccine.
AB  - Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb), remains a major
      threat to global public health. A new TB vaccine affording superior immune
      protection to M. bovis Bacillus Calmette-Guerin (BCG) is imperative. The
      advantage of a live attenuated vaccine is that it can mimic the bona fide
      pathogen, elicit immune responses similar to natural infection, and potentially
      provide more protection than other vaccines. BCG, the only vaccine and a live
      attenuated vaccine that is the result of cumulative mutations by serial passage
      of M. bovis, has provided clues for the construction of novel improved vaccines.
      A strategy is put forward for identifying a new live attenuated TB vaccine
      generated by cumulative mutation based on M.tb. Given the important role of the
      M.tb signaling network consisting of a two-component system, eukaryotic-like
      Ser/Thr protein kinase system and sigma factor system based on comparisons among
      M.tb H37Rv, M. bovis, and BCG, we have put a premium on this signaling circuit as
      the starting point for the generation of an attenuated TB vaccine. 

PMID- 24013365
TI  - The effect of race and chronic obstructive pulmonary disease on long-term
      survival after coronary artery bypass grafting.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a known predictor of
      decreased long-term survival after coronary artery bypass grafting (CABG).
      Differences in survival by race have not been examined. METHODS: A retrospective
      cohort study was conducted of CABG patients between 2002 and 2011. Long-term
      survival was compared in patients with and without COPD and stratified by race.
      Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox
      regression model. RESULTS: A total of 984 (20%) patients had COPD (black n = 182;
      white n = 802) at the time of CABG (N = 4,801).The median follow-up for study
      participants was 4.4 years. COPD was observed to be a statistically significant
      predictor of decreased survival independent of race following CABG (no COPD: HR =
      1.0; white COPD: adjusted HR = 1.9, 95% CI = 1.7-2.3; black COPD: adjusted HR =
      1.6, 95% CI = 1.1-2.2). CONCLUSION: Contrary to the expected increased risk of
      mortality among black COPD patients in the general population, a similar survival
      disadvantage was not observed in our CABG population.

PMID- 24013366
TI  - Development of an animal model to study congenital urinary obstruction.
AB  - PURPOSE: We outline the development of a reliable model of obstructive uropathy
      in fetal lambs highlighting our understanding of the critical time points for
      interventions and the variability of any such model. We identify some discoveries
      that may have clinical implications. METHODS: The model requires 60-day-gestation
      fetal lambs. In lambs, glomerulogenesis is complete by 90 days gestation. (Term
      is 145 days.) The ability to develop a reliable method of creating bladder outlet
      obstruction in females, ligating both the urethra and urachus was critical. The
      lambs are bred to an accuracy of +/-24 h. RESULTS: Creating the model at 50-60
      days gestation, produces different expressions of renal dysplasia in groups of
      lambs undergoing identical interventions at the same stage of gestation. Early
      complete urethral obstruction can produce the Potter phenotype. An appropriately
      timed vesico-amniotic shunt preserves renal development, producing a shrunken,
      non-compliant bladder. Shunting the normal fetal bladder at 80 days gestation
      produces a similar bladder. Provision of a low-pressure valve in the shunt
      preserves bladder development and compliance. Using a high-pressure shunt
      produces results similar to non-shunted lambs. DISCUSSION: We developed a
      reliable animal model for obstructive uropathy. Being alert to peripheral results
      can lead to new findings.

PMID- 24013367
TI  - Highly tunable local gate controlled complementary graphene device performing as
      inverter and voltage controlled resistor.
AB  - Using single-layer CVD graphene, a complementary field effect transistor (FET)
      device is fabricated on the top of separated back-gates. The local back-gate
      control of the transistors, which operate with low bias at room temperature,
      enables highly tunable device characteristics due to separate control over
      electrostatic doping of the channels. Local back-gating allows control of the
      doping level independently of the supply voltage, which enables device operation
      with very low VDD. Controllable characteristics also allow the compensation of
      variation in the unintentional doping typically observed in CVD graphene.
      Moreover, both p-n and n-p configurations of FETs can be achieved by
      electrostatic doping using the local back-gate. Therefore, the device operation
      can also be switched from inverter to voltage controlled resistor, opening new
      possibilities in using graphene in logic circuitry. 

PMID- 24013368
TI  - Guillain-Barre syndrome following quadrivalent human papillomavirus vaccination
      among vaccine-eligible individuals in the United States.
AB  - Post-marketing surveillance studies provide conflicting evidence about whether
      Guillain-Barre syndrome occurs more frequently following quadrivalent human
      papillomavirus (HPV4) vaccination. We aimed to assess whether Guillain-Barre
      syndrome is reported more frequently following HPV4 vaccination than other
      vaccinations among females and males aged 9 to 26 y in the United States. We used
      adverse event reports received by the United States Vaccine Adverse Event
      Reporting System (VAERS) between January 1, 2010 and December 31, 2012 to
      estimate overall, age-, and sex-specific proportional reporting ratios (PRRs) and
      corresponding Chi2 values for reports of Guillain-Barre syndrome between 5 and 42
      d following HPV vaccination. Minimum criteria for a signal using this approach
      are 3 or more cases, PRR>=2, and Chi2>=4. Guillain-Barre syndrome was listed as
      an adverse event in 45 of 14,822 reports, of which 9 reports followed HPV4
      vaccination and 36 reports followed all other vaccines. The overall, age-, and
      sex-specific PRR estimates were uniformly below 1. In addition, the overall, age
      , and sex-specific Chi2 values were uniformly below 3. Our analysis of post
      marketing surveillance data does not suggest that Guillain-Barre syndrome is
      reported more frequently following HPV4 vaccination than other vaccinations among
      vaccine-eligible females or males in the United States. Our findings may be
      useful when discussing the risks and benefits of HPV4 vaccination.

PMID- 24013370
TI  - [Hip dysplasia and spinal osteochondritis (Scheuermann's disease) in a girl with
      type II manifesting collagenopathy].
AB  - OBJECTIVES: This paper describes the natural course of irritable hip pain
      associated with spinal rigidity and pain in the thoracic region with subsequent
      development of mild kyphosis in a girl with a mutation in the collagen 2 alpha 1
      gene (type II collagenopathy). METHODS: Phenotypic and genotypic characterization
      was carried out in a 14-year-old girl to identify the underlying pathology of
      severe irritable hip pain associated with thoracic spinal rigidity and pain.
      Detailed clinical examination, skeletal survey and genetic testing were performed
      accordingly. Bernese periacetabular osteotomy was used to alleviate pain and to
      improve the anatomical correlation of the acetabular and femoral heads. RESULTS:
      Short stature associated with acetabulo-femoral dysplasia, spinal osteochondritis
      (Scheuermann's disease) and mild thoracic kyphosis were the most prominent
      abnormalities. Genetic analysis showed a heterozygous mutation in the collagen
      type II gene (COL2A1-c.1636G>A, p. G546S). A Bernese periacetabular osteotomy was
      performed to improve the clinical status of the patient. There was significant
      improvement in the extrusion index, the acetabular index and the lateral center
      edge angle. CONCLUSIONS: Hip dysplasia and Scheuermann's osteochondritis have
      never been reported in connection with a mutation in COL2A1 (collagenopathy type
      II). Awareness is needed for careful phenotypic and genotypic characterization in
      patients with irritable hip pain and spinal stiffness.

PMID- 24013372
TI  - Synthesis and characterizations of melamine-based epoxy resins.
AB  - A new, easy and cost-effective synthetic procedure for the preparation of
      thermosetting melamine-based epoxy resins is reported. By this innovative
      synthetic method, different kinds of resins can be obtained just by mixing the
      reagents in the presence of a catalyst without solvent and with mild curing
      conditions. Two types of resins were synthesized using melamine and a glycidyl
      derivative (resins I) or by adding a silane derivative (resin II). The resins
      were characterized by means of chemical-physical and thermal techniques.
      Experimental results show that all the prepared resins have a good thermal
      stability, but differ for their mechanical properties: resin I exhibits
      remarkable stiffness with a storage modulus value up to 830 MPa at room
      temperature, while lower storage moduli were found for resin II, indicating that
      the presence of silane groups could enhance the flexibility of these materials.
      The resins show a pot life higher than 30 min, which makes these resins good
      candidates for practical applications. The functionalization with silane
      terminations can be exploited in the formulation of hybrid organic-inorganic
      composite materials.

PMID- 24013371
TI  - ARF1 and SAR1 GTPases in endomembrane trafficking in plants.
AB  - Small GTPases largely control membrane traffic, which is essential for the
      survival of all eukaryotes. Among the small GTP-binding proteins, ARF1 (ADP
      ribosylation factor 1) and SAR1 (Secretion-Associated RAS super family 1) are
      commonly conserved among all eukaryotes with respect to both their functional and
      sequential characteristics. The ARF1 and SAR1 GTP-binding proteins are involved
      in the formation and budding of vesicles throughout plant endomembrane systems.
      ARF1 has been shown to play a critical role in COPI (Coat Protein Complex I)
      mediated retrograde trafficking in eukaryotic systems, whereas SAR1 GTPases are
      involved in intracellular COPII-mediated protein trafficking from the ER to the
      Golgi apparatus. This review offers a summary of vesicular trafficking with an
      emphasis on the ARF1 and SAR1 expression patterns at early growth stages and in
      the de-etiolation process.

PMID- 24013373
TI  - Self-organizing cyclolinear organosilicon polymers in bulk and on the surface of
      water.
AB  - Cyclolinear organocarbosiloxane polymers with varying content and location of
      (CH2)n groups in the monomer unit were synthesized by reactions of
      heterofunctional polycondensation and polyaddition of difunctional
      organocyclosiloxanes and organocyclocarbosiloxanes. Their bulk properties were
      studied by differential scanning calorimetry and X-ray structural analysis. It
      was shown that on introduction of CH2 groups into the methylcyclohexasiloxane
      unit, the polymer retains the ability to self-organize with formation of a
      mesomorphic state in a wide temperature range, while on introduction of (CH2)2
      fragments in a cyclotetrasiloxane unit or in a bridge connecting two
      methylcyclotetra(hexa)siloxane units it does not. Comparison of the X-ray data of
      dihydroxy derivatives of decamethylcyclohexasiloxane and decamethyl-5
      carbocyclohexasiloxane with packing of cyclolinear organosilicon polymers in bulk
      shows that the polymer inherits the layered type of crystalline structure typical
      for monomers. Langmuir films of cyclolinear polymethylcarbosiloxanes with
      different design of monomer units were studied as well. It was revealed that all
      polymers form monomolecular films at the air/water interface, excluding those
      having longer hydrophobic fragment than hydrophilic ones. The ability to form
      multilayers depends on the surroundings of Si atom in the bridge between the
      cycles.

PMID- 24013374
TI  - Bicistronic gene transfer tools for delivery of miRNAs and protein coding
      sequences.
AB  - MicroRNAs (miRNAs) are a category of small RNAs that modulate levels of proteins
      via post-transcriptional inhibition. Currently, a standard strategy to
      overexpress miRNAs is as mature miRNA duplexes, although this method is
      cumbersome if multiple miRNAs need to be delivered. Many of these miRNAs are
      found within introns and processed through the RNA polymerase II pathway. We have
      designed a vector to exploit this naturally-occurring intronic pathway to deliver
      the three members of the sensory-specific miR-183 family from an artificial
      intron. In one version of the vector, the downstream exon encodes the reporter
      (GFP) while another version encodes a fusion protein created between the
      transcription factor Atoh1 and the hemaglutinin epitope, to distinguish it from
      endogenous Atoh1. In vitro analysis shows that the miRNAs contained within the
      artificial intron are processed and bind to their targets with specificity. The
      genes downstream are successfully translated into protein and identifiable
      through immunofluorescence. More importantly, Atoh1 is proven functional through
      in vitro assays. These results suggest that this cassette allows expression of
      miRNAs and proteins simultaneously, which provides the opportunity for joint
      delivery of specific translational repressors (miRNA) and possibly
      transcriptional activators (transcription factors). This ability is attractive
      for future gene therapy use.

PMID- 24013375
TI  - Neuroprotective effects of alpha-tocotrienol on kainic acid-induced neurotoxicity
      in organotypic hippocampal slice cultures.
AB  - Vitamin E, such as alpha-tocopherol (ATPH) and alpha-tocotrienol (ATTN), is a
      chain-breaking antioxidant that prevents the chain propagation step during lipid
      peroxidation. In the present study, we investigated the effects of ATTN on KA
      induced neuronal death using organotypic hippocampal slice culture (OHSC) and
      compared the neuroprotective effects of ATTN and ATPH. After 15 h KA (5 uM)
      treatment, delayed neuronal death was detected in the CA3 region and reactive
      oxygen species (ROS) formation and lipid peroxidation were also increased. Both
      co-treatment and post-treatment of ATPH (100 uM) or ATTN (100 uM) significantly
      increased the cell survival and reduced the number of TUNEL-positive cells in the
      CA3 region. Increased dichlorofluorescein (DCF) fluorescence and levels of
      thiobarbiturate reactive substances (TBARS) were decreased by ATPH and ATTN
      treatment. These data suggest that ATPH and ATTN treatment have protective
      effects on KA-induced cell death in OHSC. ATTN treatment tended to be more
      effective than ATPH treatment, even though there was no significant difference
      between ATPH and ATTN in co-treatment or post-treatment.

PMID- 24013376
TI  - Magnetic nanosystem for cancer therapy using oncocalyxone a, an antitomour
      secondary metabolite isolated from a Brazilian plant.
AB  - This paper describes the investigation and development of a novel magnetic drug
      delivery nanosystem (labeled as MO-20) for cancer therapy. The drug employed was
      oncocalyxone A (onco A), which was isolated from Auxemma oncocalyx, an endemic
      Brazilian plant. It has a series of pharmacological properties: antioxidant,
      cytotoxic, analgesic, anti-inflammatory, antitumor and antiplatelet. Onco A was
      associated with magnetite nanoparticles in order to obtain magnetic properties.
      The components of MO-20 were characterized by XRD, FTIR, TGA, TEM and
      Magnetization curves. The MO-20 presented a size of about 30 nm and globular
      morphology. In addition, drug releasing experiments were performed, where it was
      observed the presence of the anomalous transport. The results found in this work
      showed the potential of onco A for future applications of the MO-20 as a new
      magnetic drug release nanosystem for cancer treatment.

PMID- 24013379
TI  - Design of phosphonium-type zwitterion as an additive to improve saturated water
      content of phase-separated ionic liquid from aqueous phase toward reversible
      extraction of proteins.
AB  - We designed phosphonium-type zwitterion (ZI) to control the saturated water
      content of separated ionic liquid (IL) phase in the hydrophobic IL/water biphasic
      systems. The saturated water content of separated IL phase, 1-butyl-3
      methyimidazolium bis(trifluoromethanesulfonyl)imide, was considerably improved
      from 0.4 wt% to 62.8 wt% by adding N,N,N-tripentyl-4-sulfonyl-1-butanephosphonium
      type ZI (P555C4S). In addition, the maximum water content decreased from 62.8 wt%
      to 34.1 wt% by increasing KH2PO4/K2HPO4 salt content in upper aqueous phosphate
      buffer phase. Horse heart cytochrome c (cyt.c) was dissolved selectively in IL
      phase by improving the water content of IL phase, and spectroscopic analysis
      revealed that the dissolved cyt.c retained its higher ordered structure.
      Furthermore, cyt. c dissolved in IL phase was re-extracted again from IL phase to
      aqueous phase by increasing the concentration of inorganic salts of the buffer
      solution.

PMID- 24013377
TI  - Experimental models of status epilepticus and neuronal injury for evaluation of
      therapeutic interventions.
AB  - This article describes current experimental models of status epilepticus (SE) and
      neuronal injury for use in the screening of new therapeutic agents. Epilepsy is a
      common neurological disorder characterized by recurrent unprovoked seizures. SE
      is an emergency condition associated with continuous seizures lasting more than
      30 min. It causes significant mortality and morbidity. SE can cause devastating
      damage to the brain leading to cognitive impairment and increased risk of
      epilepsy. Benzodiazepines are the first-line drugs for the treatment of SE,
      however, many people exhibit partial or complete resistance due to a breakdown of
      GABA inhibition. Therefore, new drugs with neuroprotective effects against the SE
      induced neuronal injury and degeneration are desirable. Animal models are used to
      study the pathophysiology of SE and for the discovery of newer anticonvulsants.
      In SE paradigms, seizures are induced in rodents by chemical agents or by
      electrical stimulation of brain structures. Electrical stimulation includes
      perforant path and self-sustaining stimulation models. Pharmacological models
      include kainic acid, pilocarpine, flurothyl, organophosphates and other
      convulsants that induce SE in rodents. Neuronal injury occurs within the initial
      SE episode, and animals exhibit cognitive dysfunction and spontaneous seizures
      several weeks after this precipitating event. Current SE models have potential
      applications but have some limitations. In general, the experimental SE model
      should be analogous to the human seizure state and it should share very similar
      neuropathological mechanisms. The pilocarpine and diisopropylfluorophosphate
      models are associated with prolonged, diazepam-insensitive seizures and
      neurodegeneration and therefore represent paradigms of refractory SE. Novel
      mechanism-based or clinically relevant models are essential to identify new
      therapies for SE and neuroprotective interventions.

PMID- 24013378
TI  - Noncoding RNA in oncogenesis: a new era of identifying key players.
AB  - New discoveries and accelerating progresses in the field of noncoding RNAs
      (ncRNAs) continuously challenges our deep-rooted doctrines in biology and
      sometimes our imagination. A growing body of evidence indicates that ncRNAs are
      important players in oncogenesis. While a stunning list of ncRNAs has been
      discovered, only a small portion of them has been examined for their biological
      activities and very few have been characterized for the molecular mechanisms of
      their action. To date, ncRNAs have been shown to regulate a wide range of
      biological processes, including chromatin remodeling, gene transcription, mRNA
      translation and protein function. Dysregulation of ncRNAs contributes to the
      pathogenesis of a variety of cancers and aberrant ncRNA expression has a high
      potential to be prognostic in some cancers. Thus, a new cancer research era has
      begun to identify novel key players of ncRNAs in oncogenesis. In this review, we
      will first discuss the function and regulation of miRNAs, especially focusing on
      the interplay between miRNAs and several key cancer genes, including p53, PTEN
      and c-Myc. We will then summarize the research of long ncRNAs (lncRNAs) in
      cancers. In this part, we will discuss the lncRNAs in four categories based on
      their activities, including regulating gene expression, acting as miRNA decoys,
      mediating mRNA translation, and modulating protein activities. At the end, we
      will also discuss recently unraveled activities of circular RNAs (circRNAs).

PMID- 24013382
TI  - Bio-functionalization of multi-walled carbon nanotubes.
AB  - Here we present a hybrid approach to functionalize multi-walled carbon nanotubes
      in aqueous solution, exploring a non-covalent binding strategy. We focus on
      formation of hybrid complexes consisting of carbon nanotubes decorated by single
      stranded DNA, non-covalently attached using surfactants as intermediate layers.
      Unlike single walled carbon nanotubes, revealing easy side wall wrapping of DNA,
      we observe that wrapping of nucleic acids around multi-walled carbon nanotubes is
      diameter dependent. 

PMID- 24013381
TI  - Solitary fibrous tumor of the thyroid gland.
AB  - Solitary fibrous tumor is a spindle cell neoplasm rarely arising in the thyroid
      gland. We present a 78-year-old man with the diagnosis of solitary fibrous tumor
      of the thyroid gland resected by subtotal thyroidectomy. Fine needle aspiration
      cytology via ultrasound guidance demonstrated a hypocellular aspirate that
      revealed follicular epithelial cells with mild nuclear atypia and scattered
      spindle cells with bland nuclei. Histologically, the patternless proliferation of
      spindle cells was seen among collagenous bundles, accompanied by
      hemangiopericytomatous vessels, and variously dilated follicles with mild
      atypical cells having slightly enlarged nuclei, indicating adenomatous goiter.
      The neoplastic spindle cells showed diffuse immunoreactivity to CD34, bcl-2, CD99
      and vimentin, but were negative for cytokeratins, calcitonin, TTF-1 and CD5.
      Although solitary fibrous tumor arising in thyroid gland is rare, this tumor
      should be included in the differential diagnosis of thyroid spindle cell tumors
      and also that of adenomatous. 

PMID- 24013380
TI  - The role of initial oligomers in amyloid fibril formation by human stefin B.
AB  - Oligomers are commonly observed intermediates at the initial stages of amyloid
      fibril formation. They are toxic to neurons and cause decrease in neural
      transmission and long-term potentiation. We describe an in vitro study of the
      initial steps in amyloid fibril formation by human stefin B, which proved to be a
      good model system. Due to relative stability of the initial oligomers of stefin
      B, electrospray ionization mass spectrometry (ESI MS) could be applied in
      addition to size exclusion chromatography (SEC). These two techniques enabled us
      to separate and detect distinguished oligomers from the monomers: dimers,
      trimers, tetramers, up to decamers. The amyloid fibril formation process was
      followed at different pH and temperatures, including such conditions where the
      process was slow enough to detect the initial oligomeric species at the very
      beginning of the lag phase and those at the end of the lag phase. Taking into
      account the results of the lower-order oligomers transformations early in the
      process, we were able to propose an improved model for the stefin B fibril
      formation.

PMID- 24013383
TI  - Expression of the chemokine decoy receptor D6 is decreased in colon
      adenocarcinomas.
AB  - Recruitment of immune cells to tumors is a complex process crucial for both
      inflammation-driven tumor progression and specific anti-tumor cytotoxicity.
      Chemokines control the directed migration of immune cells, and their actions are
      partly controlled by nonsignaling chemokine decoy receptors. The role of the
      receptors such as D6, Duffy antigen receptor for chemokines and ChemoCentryx
      chemokine receptor in immunity to tumors is still unclear. Using real-time PCR,
      we detected significantly decreased expression of D6 mRNA in colon tumors
      compared to unaffected mucosa. D6 protein was expressed by lymphatic endothelium
      and mononuclear cells in the colon lamina propria and detected by
      immunohistochemistry in two out of six tissue samples containing high D6 mRNA
      levels, whereas no staining was observed in any tissue samples expressing low
      mRNA levels. When examining the density of lymphatic vessels in colon tumors, we
      detected a marked increase in vessels identified by the lymphatic endothelial
      marker Lyve-1, excluding passive regulation of D6 due to decreased lymphatic
      vessel density. In parallel, the Treg-recruiting chemokine CCL22, which is
      sequestered by D6, was threefold increased in tumor tissue. Furthermore, we could
      show that low D6 expression correlated to more invasive tumors and that tumor
      location influences D6 expression, which is lower in the more distal parts of the
      colon. The data support that regulation of D6 by colon tumors results in altered
      levels of proinflammatory CC chemokines, thereby shaping the local chemokine
      network to favor tumor survival. This may have implications for the design of
      future immunotherapy for colon cancer. 

PMID- 24013384
TI  - Post-marketing study on the safety of a meningococcal group A, C bivalent
      polysaccharide conjugate vaccine.

PMID- 24013385
TI  - G-quadruplex unfolding in higher-order DNA structures.
AB  - G-quadruplex unfolding within a sequence of two quadruplex units was
      characterized by gel electrophoresis, calorimetry and spectroscopy. The obtained
      results suggest that the kinetics and thermodynamics of the individual quadruplex
      unfolding are affected by its interaction with other DNA secondary structural
      elements. 

PMID- 24013386
TI  - Population genetics of Mediterranean and Saharan olives: geographic patterns of
      differentiation and evidence for early generations of admixture.
AB  - BACKGROUND AND AIMS: The olive (Olea europaea subsp. europaea) was domesticated
      in the Mediterranean area but its wild relatives are distributed over three
      continents, from the Mediterranean basin to South Africa and south-western Asia.
      Recent studies suggested that this crop originated in the Levant while a
      secondary diversification occurred in most westward areas. A possible
      contribution of the Saharan subspecies (subsp. laperrinei) has been highlighted,
      but the data available were too limited to draw definite conclusions. Here,
      patterns of genetic differentiation in the Mediterranean and Saharan olives are
      analysed to test for recent admixture between these taxa. METHODS: Nuclear
      microsatellite and plastid DNA (ptDNA) data were compiled from previous studies
      and completed for a sample of 470 cultivars, 390 wild Mediterranean trees and 270
      Saharan olives. A network was reconstructed for the ptDNA haplotypes, while a
      Bayesian clustering method was applied to identify the main gene pools in the
      data set and then simulate and test for early generations of admixture between
      Mediterranean and Saharan olives. KEY RESULTS: Four lineages of ptDNA haplotypes
      are recognized: three from the Mediterranean basin and one from the Sahara. Only
      one haplotype, primarily distributed in the Sahara, is shared between laperrinei
      and europaea. This haplotype is detected once in 'Dhokar', a cultivar from the
      Maghreb. Nuclear microsatellites show geographic patterns of genetic
      differentiation in the Mediterranean olive that reflect the primary origins of
      cultivars in the Levant, and indicate a high genetic differentiation between
      europaea and laperrinei. No first-generation hybrid between europaea and
      laperrinei is detected, but recent, reciprocal admixture between Mediterranean
      and Saharan subspecies is found in a few accessions, including 'Dhokar'.
      CONCLUSIONS: This study reports for the first time admixture between
      Mediterranean and Saharan olives. Although its contribution remains limited,
      Laperrine's olive has been involved in the diversification of cultivated olives.

PMID- 24013387
TI  - Decomposing the seasonal fitness decline.
AB  - Seasonal fitness declines are common, but the relative contribution of different
      reproductive components to the seasonal change in the production of reproductive
      young, and the component-specific drivers of this change is generally poorly
      known. We used long-term data (17 years) on breeding time (i.e. date of first egg
      laid) in northern wheatears (Oenanthe oenanthe) to investigate seasonal
      reproductive patterns and estimate the relative contributions of reproductive
      components to the overall decline in reproduction, while accounting for factors
      potentially linked to seasonal declines, i.e. individual and habitat quality. All
      reproductive components-nest success (reflecting nest predation rate), clutch
      size, fledging success and recruitment success-showed a clear decline with
      breeding time whereas subsequent adult survival did not. A non-linear increase in
      nest predation rate caused nest success to decline rapidly early in the season
      and level off at ~80% success late in the breeding season. The combined seasonal
      decline in all reproductive components caused the mean production of recruits per
      nest to drop from around 0.7-0.2; with the relative contribution greatest for
      recruitment success which accounted for ~50% of the decline. Our data suggest
      that changing environmental conditions together with effects of nest predation
      have strong effects on the seasonal decline in fitness. Our demonstration of the
      combined effects of all reproductive components and their relative contribution
      shows that omitting data from later stages of breeding (recruitment) can greatly
      underestimate seasonal fitness declines.

PMID- 24013388
TI  - Mycoplasma fermentans inhibits the activity of cellular DNA topoisomerase I by
      activation of PARP1 and alters the efficacy of its anti-cancer inhibitor.
AB  - To understand the effects of the interaction between Mycoplasma and cells on the
      host cellular function, it is important to elucidate the influences of infection
      of cells with Mycoplasma on nuclear enzymes such as DNA Topoisomerase type I
      (Topo I). Human Topo I participates in DNA transaction processes and is the
      target of anti-cancer drugs, the camptothecins (CPTs). Here we investigated the
      mechanism by which infection of human tumor cells with Mycoplasma fermentans
      affects the activity and expression of cellular Topo I, and the anti-cancer
      efficacy of CPT. Human cancer cells were infected or treated with live or
      sonicated M. fermentans and the activity and expression of Topo I was determined.
      M. fermentans significantly reduced (by 80%) Topo I activity in the
      infected/treated tumor cells without affecting the level of Topo I protein. We
      demonstrate that this reduction in enzyme activity resulted from ADP-ribosylation
      of the Topo I protein by Poly-ADP-ribose polymerase (PARP-1). In addition, pERK
      was activated as a result of the induction of the MAPK signal transduction
      pathway by M. fermentans. Since PARP-1 was shown to be activated by pERK, we
      concluded that M. fermentans modified the cellular Topo I activity by activation
      of PARP-I via the induction of the MAPK signal transduction pathway. Moreover,
      the infection of tumor cells with M. fermentans diminished the inhibitory effect
      of CPT. The results of this study suggest that modification of Topo I activity by
      M. fermentans may alter cellular gene expression and the response of tumor cells
      to Topo I inhibitors, influencing the anti-cancer capacity of Topo I antagonists.

PMID- 24013389
TI  - Decay chains and photofission investigation based on nuclear spectroscopy of
      highly enriched uranium sample.
AB  - Nuclear spectroscopy experiments were performed for 100g metallic uranium rod
      enriched to 93% (235)U, in order to establish and characterize the most prominent
      gamma-rays in the natural decay series and photofission reaction. Single gamma
      ray spectra and gamma-gamma coincidences measurements were conducted before
      irradiation. The uranium sample was subsequently irradiated with 15 MeV
      bremsstrahlung photons. Relative intensities of gamma-lines and several values of
      half-lives of the fission fragments decays were determined. The obtained
      information can be utilized in detection of smuggled nuclear materials and
      characterization of bulky nuclear waste packages.

PMID- 24013390
TI  - Evidence for two modes of synergistic induction of apoptosis by mapatumumab and
      oxaliplatin in combination with hyperthermia in human colon cancer cells.
AB  - Colorectal cancer is the third leading cause of cancer-related mortality in the
      world--the main cause of death from colorectal cancer is hepatic metastases,
      which can be treated with isolated hepatic perfusion (IHP). Searching for the
      most clinically relevant approaches for treating colorectal metastatic disease by
      isolated hepatic perfusion (IHP), we developed the application of oxaliplatin
      concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody
      mapatumumab (Mapa), and investigated the molecular mechanisms of this
      multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well
      as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this
      study, that the synergistic effect of the multimodality treatment-induced
      apoptosis was caspase dependent and activated death signaling via both the
      extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was
      activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL
      phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL,
      which contributed to the intrinsic pathway. The downregulation of cellular FLICE
      inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was
      accomplished through ubiquitination at lysine residue (K) 195 and protein
      synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant
      (S62A) completely abrogated the synergistic effect. The successful outcome of
      this study supports the application of multimodality strategy to patients with
      colorectal hepatic metastases who fail to respond to standard chemoradiotherapy
      that predominantly targets the mitochondrial apoptotic pathway.

PMID- 24013391
TI  - Short-term evaluation of bioactive glass using the modified osteotome sinus
      elevation technique.
AB  - PURPOSE: The aim of this retrospective study was to evaluate the dimensional
      changes of bioactive glass (BG) that occur after sinus bone grafting using a
      modified osteotome technique and simultaneous implant placement. METHODS: Seventy
      six subjects received 87 implants with a modified osteotome sinus elevation
      technique using BG bone graft and simultaneous implant placement. The radiographs
      taken at the time of implant placement and at the time of implant uncovery were
      retrospectively evaluated to assess the degree of BG dimensional changes.
      RESULTS: Thirty-six subjects with 44 implants were included in the study. A 24.6%
      significant reduction (P < 0.0001) of the apical height of the BG from the apex
      of the implant occurred during the 6-month healing period. There was no
      significant correlation between the extent of sinus floor elevation, healing
      time, and the vertical distance the implant penetrated into the sinus with the
      degree of the dimensional changes of the bone graft. CONCLUSIONS: This study
      demonstrated that BG had a dimensional change reduction of 24.6% after 6 months
      of healing time.

PMID- 24013392
TI  - Immediate free iliac bone graft after nonsegmental mandibular resection and
      delayed implant placement: a case series.
AB  - BACKGROUND: Resection of mandibular tumors without proper reconstruction may lead
      to unfavorable esthetic and function results. The purpose of this case series was
      to describe clinical results and a technique to prevent tissue loss using
      nonvascular iliac grafts immediately following tumor resection and long-term
      stability of the implants. MATERIALS AND METHODS: Three female patients presented
      with oral neoplasms (2 ameloblastoma and 1 ossifying fibroma). The mandibular
      reconstruction was performed with nonvascularized iliac grafts simultaneous with
      tumor removal. Subsequently, 10 dental implants were placed 6 to 9 months after
      reconstruction and restored. Survival and success of the implants were evaluated.
      RESULTS: Marginal mandibulectomy in 1 patient and buccal bone resection in 2
      patients was performed; the resection sites were reconstructed with an immediate
      nonvascularized iliac graft. All implants survived and were successful during
      follow-up periods between 44 and 105 months. Mean marginal bone loss of 10
      implants was 0.09 mm. CONCLUSIONS: Immediate reconstruction with nonvascularized
      iliac grafts following tumor resection may be a viable treatment option for
      nonsegmental inlay osseous defects. In these case series, the resorption of the
      iliac bone was minimal after 6 to 9 months consolidation periods.

PMID- 24013393
TI  - Primary stability determination of implants inserted in sinus augmented sites: 1
      step versus 2-step procedure.
AB  - OBJECTIVES: The aim of this study was to evaluate the primary stability of
      implants placed immediately after a sinus lift, compared with implants placed in
      the area treated with a sinus lift 6 months before. MATERIAL AND METHODS:
      Patients with a residual bone height of at least 4 mm were treated with a 1-stage
      procedure (group A) and patients with a residual bone height < 4 mm with a 2
      stage approach (group B). Sinus lift was always performed with 50% autogenous
      bone and 50% deproteinized bovine bone mineral. Data recorded included maximum
      insertion torque (IT), resonance frequency analysis (RFA) values, and bone
      density, length, and diameter. It was recorded whether an implant was removed
      within 6 months after insertion. RESULTS: Fourteen patients were included in
      group A and 16 patients in group B; 96 implants were inserted. Mean IT was 23.77
      +/- 12.63 N.cm in group A and 26.48 +/- 20.80 N.cm in group B. Mean RFA was 65.25
      +/- 4.45 implant stability quotient (ISQ) in group A and 67.92 +/- 10.99 ISQ in
      group B. No statistically significant differences were found. All implants were
      osseointegrated. CONCLUSIONS: The results show that the implants studied can
      obtain a sufficient primary stability in both clinical situations without
      statistically significant differences.

PMID- 24013394
TI  - Implant-abutment connection designs for anterior crowns: reliability and failure
      modes.
AB  - OBJECTIVES: To investigate the effect of implant-abutment connection types on
      reliability and failure modes of anterior single-unit crowns. METHODS: Fifty-four
      implants were divided in 3 groups (n = 18 each): external hexagon (EH), internal
      hexagon (IH), and Morse taper (MT) connection. Abutments were screwed to the
      implants, and maxillary central incisor metal crowns were cemented and subjected
      to step-stress accelerated life testing. RESULTS: The beta values derived from
      use-level probability Weibull calculations for groups IH (2.52), EH (1.67), and
      MT (0.88) indicated that fatigue influenced the failure only of IH and EH groups.
      The reliability for a mission of 100,000 cycles at 175 N was 0.99 (0.98-1.00),
      0.84 (0.62-0.94) and 0.97 (0.87-0.99) for the EH, IH, and MT, respectively. The
      characteristic strength was not significantly different between EH (290 N) and IH
      (251 N) but significantly higher for MT (357 N). For IH and EH groups, failure
      involved screw fracture, and the MT implants primary failure mode was abutment
      fracture. CONCLUSIONS: Reliability was higher for the EH and MT relative to IH
      groups, whereas the characteristic strength was significantly higher for implants
      with MT connection.

PMID- 24013395
TI  - Effects of polishing methods on Candida albicans adhesion on cast pure titanium
      surfaces.
AB  - OBJECTIVE: To explore the effects of different polishing methods on Candida
      albicans adhesion to cast pure titanium surfaces. METHODS: Pure titanium test
      specimens randomly divided into 4 groups: not specially treated (CT), manual
      polishing (MPT), electrolytic polishing (EPT), and centrifugal barrel polishing
      (CPT). Surface roughness was measured with surface profilometer. Contact angles
      of water, diiodomethane, and ethylene glycol on specimen surface were measured,
      and the free energy was calculated. Each group were immersed in a C. albicans
      suspension for 48 hours, and cell count of C. albicans adhesion were taken.
      Morphology of C. albicans adhesion was observed by SEM. RESULTS: Surface
      roughness (Ra) were in the following order: CT > EPT > MPT > CPT. The amount of
      C. albicans adhesion to the surface of CPT was significantly less than CT, MPT,
      and EPT by cells count (P < 0.05). In SEM, less C. albicans aggregation formed on
      the surface of CPT than other 3 groups. CONCLUSIONS: Specimens treated by the CPT
      method showed superior effect to the specimens treated with MPT and EPT methods
      in reducing the adhesion of C. albicans.

PMID- 24013396
TI  - Prosthodontic rehabilitation in patient with ectodermal dysplasia combining
      preprosthetic techniques: a case report.
AB  - Oral manifestations in ectodermal dysplasia include oligodontia, alveolar ridges
      hypoplasia, and others. Due to the special conditions in terms of unhealthy teeth
      and lack of bone, implant-supported rehabilitation seems to offer the most
      satisfactory outcome. A 27-year-old male diagnosed with ectodermal dysplasia was
      referred to our department for oral rehabilitation. Oral manifestations included
      oligodontia, maxillary and mandibular atrophy, mandibular alveolar ridge with
      knife-edge morphology, and conical teeth. Treatment planning consisted of a Le
      Fort I osteotomy with interpositional grafts, bilateral sinus lift, and placement
      of maxillary and mandibular inlay and onlay corticocancellous grafts, using
      autologous iliac crest bone. In the second surgery, all remaining teeth were
      removed and 11 endosteal implants were placed. Six months after implant
      placement, a bimaxillary fixed implant-supported prosthesis was delivered,
      maintaining a satisfactory esthetic and functional result after a 2-year follow
      up. The use of combined preprosthetic techniques allows the placement of
      endosteal implants and a fixed implant-supported prosthesis in patients with
      oligodontia and ectodermal dysplasia, providing an esthetic and functional oral
      rehabilitation. 

PMID- 24013397
TI  - Effect of clinical factors on bacterial contamination of bone chips collected
      during implant surgery.
AB  - PURPOSE: The objective of this study was to investigate the relationship between
      various clinical factors and bacterial contamination of bone chips (BC) collected
      during dental implant surgery and to elucidate how bacterial contamination might
      be minimized. MATERIALS AND METHODS: Implants were installed in 55 partially
      edentulous patients (36 men and 19 women), among whom the relationship between
      various clinical factors and bacterial contamination of BC collected by bone trap
      was investigated in 37. The effect of rinsing with a saline on BC was determined
      in 18 patients. Number of contaminating microorganisms was expressed as colony
      forming units (CFUs). RESULTS: CFUs in the maxilla were lower than those in the
      mandible (P < 0.01). CFUs at the incisors or canines were lower than those at the
      premolars or molars (P < 0.01). Logistic regression analysis revealed a
      relationship between average bacterial count and duration of surgery (odds ratio,
      1.046; 95% CI, 1.012-1.081). Rinsing of BC reduced bacterial contamination.
      CONCLUSION: Duration of surgery is a major clinical factor affecting
      contamination risk in BC, and rinsing of BC with a sterile saline solution
      reduces bacterial number.

PMID- 24013398
TI  - Implant surface detoxification: a comprehensive review.
AB  - OBJECTIVE: Nonsurgical treatment has been shown to be effective in dealing with
      inflammatory lesions around implant without bone loss. However, when bone loss is
      noticed, surgical treatment may be needed. Nonetheless, before the surgical
      approaches can be effective, the contaminated implant surface has to be
      detoxified. Many detoxifying agents/techniques have been proposed and have shown
      varieties of outcomes, these include but not limited to: citric acid,
      chlorhexidine, local and systemic antibiotics, hydrogen peroxide, air-powder
      abrasive, laser and photodynamic therapy, and implantoplasty using burs. Hence,
      the aim of this review was to evaluate them in terms of their ability in
      achieving implant surface detoxification. MATERIALS AND METHODS: A search of
      PubMed and a hand search of articles were conducted up to December 2011.
      Different keywords related to the treatment of peri-implant diseases were used.
      RESULTS: At this time, all techniques/agents have shown to be equally effective
      to detoxify the contaminated implant surface. CONCLUSION: Comparative studies of
      different detoxification methods are heterogeneous, leaving a few voids when
      selecting a specific technique for detoxifying the contaminated implant surface.

PMID- 24013399
TI  - Ridge width gain with screw spreaders: a cadaver study.
AB  - BACKGROUND: The aim of this cadaver study was to evaluate the amount of ridge
      expansion with screw spreaders. METHODS: Eleven edentulous maxillae providing 20
      eligible sites were used. Ridges with initial width of 3 to 6 mm were expanded
      using a set of 6 screw spreaders, and implants (o3.7 * 10 mm) were subsequently
      placed. Ridge width at 2 mm apical to the crest was measured at the baseline,
      after expansion, and implant placement. Buccal plate thickness and incidence of
      buccal dehiscence after implant placement were measured. RESULTS: The mean
      initial ridge width was 3.97 +/- 0.82 mm. After the expansion, the mean ridge
      width increased to 4.76 +/- 0.77 mm (Delta = 0.79 mm). Majority of sites (7/9
      sites) with an initial ridge width of <4 mm had a buccal dehiscence after implant
      placement. A buccal plate thickness of >=1 mm was consistently present in cases
      with an initial ridge width of >=4.5 mm after implant placement. CONCLUSIONS: The
      screw spreaders had a modest effect on ridge expansion. Their use might be
      limited because additional bone augmentation might be required to prevent or
      correct the bony dehiscence encountered in ridges <4.5 mm wide. Therefore, using
      this particular instrument kit for horizontal ridge augmentation is only
      indicated in specific cases.

PMID- 24013400
TI  - Vertically aligned nanostructures based on Na-doped ZnO nanorods for wide band
      gap semiconductor memory applications.
AB  - Vertically aligned undoped ZnO nanotips, nanotubes and nanorods were synthesized
      on the top facets of Na-doped ZnO nanorods without catalytic assistance under
      different growth times in a chemical vapor deposition system. The growth
      mechanism is discussed. The Na-doped nanorods were grown on a ZnO seed layer on
      Si. The p-type conductivity of the Na-doped nanorods was studied by temperature
      dependent photoluminescence and nanorod back-gated field effect transistor
      measurements. The undoped nanorods, Na-doped nanorods and undoped seed layer form
      an n-p-n memory structure. The programming and retention characteristics have
      been demonstrated. 

PMID- 24013401
TI  - Preliminary evidence suggesting caution in the use of psychiatric self-report
      measures with adolescents with high-functioning autism spectrum disorders.
AB  - This study investigated the utility of self-report measures to screen for
      psychiatric comorbidities in autism spectrum disorders (ASDs). Thirty-eight 10-17
      year olds with an ASD and without mental retardation completed: the Children's
      Depression Inventory-Short version (CDI-S), Revised Children's Manifest Anxiety
      Scale (RCMAS), Conners-Wells Adolescent Self-report Scale-Short edition (CASS-S),
      and Short Leyton Obsessional Inventory-Child Version (SLOI-CV). Their parents
      were interviewed with the Autism Comorbidity Interview-Present and Lifetime (ACI
      PL) to establish psychiatric diagnoses. Sensitivity, specificity, positive and
      negative predictive values, and reliability coefficients were calculated for each
      self-report and compared to values from literature. The CDI-S and CASS-S yielded
      a high number of false negatives, with lower sensitivities and specificities in
      the sample than the literature. There was a nearly significant difference in
      total mean RCMAS scores between participants with and without anxiety, though
      again the means for both groups were below the threshold of concern. The SLOI-CV
      yielded a high false positive rate. All four instruments had reliability
      coefficients comparable to literature values. Results must be considered
      preliminary due to sample size. However, the findings suggest that although self
      report instruments may provide useful information in the diagnosis of psychiatric
      comorbidities in ASD, caution must be exercised in their interpretation.

PMID- 24013402
TI  - RecG and UvsW catalyse robust DNA rewinding critical for stalled DNA replication
      fork rescue.
AB  - Helicases that both unwind and rewind DNA have central roles in DNA repair and
      genetic recombination. In contrast to unwinding, DNA rewinding by helicases has
      proved difficult to characterize biochemically because of its thermodynamically
      downhill nature. Here we use single-molecule assays to mechanically destabilize a
      DNA molecule and follow, in real time, unwinding and rewinding by two DNA repair
      helicases, bacteriophage T4 UvsW and Escherichia coli RecG. We find that both
      enzymes are robust rewinding enzymes, which can work against opposing forces as
      large as 35 pN, revealing their active character. The generation of work during
      the rewinding reaction allows them to couple rewinding to DNA unwinding and/or
      protein displacement reactions central to the rescue of stalled DNA replication
      forks. The overall results support a general mechanism for monomeric rewinding
      enzymes.

PMID- 24013403
TI  - SOX2 and OCT4 mRNA-expressing cells, detected by molecular beacons, localize to
      the center of neurospheres during differentiation.
AB  - Neurospheres are used as in vitro assay to measure the properties of neural stem
      cells. To investigate the molecular and phenotypic heterogeneity of neurospheres,
      molecular beacons (MBs) targeted against the stem cell markers OCT4 and SOX2 were
      designed, and synthesized with a 2'-O-methyl RNA backbone. OCT4 and SOX2 MBs were
      transfected into human embryonic mesencephalon derived cells, which spontaneously
      form neurospheres when grown on poly-L-ornitine/fibronectin matrix and medium
      complemented with bFGF. OCT4 and SOX2 gene expression were tracked in individual
      cell using the MBs. Quantitative image analysis every day for seven days showed
      that the OCT4 and SOX2 mRNA-expressing cells clustered in the centre of the
      neurospheres cultured in differentiation medium. By contrast, cells at the
      periphery of the differentiating spheres developed neurite outgrowths and
      expressed the tyrosine hydroxylase protein, indicating terminal differentiation.
      Neurospheres cultured in growth medium contained OCT4 and SOX2-positive cells
      distributed throughout the entire sphere, and no differentiating neurones. Gene
      expression of SOX2 and OCT4 mRNA detected by MBs correlated well with gene and
      protein expression measured by qRT-PCR and immunostaining, respectively. These
      experimental data support the theoretical model that stem cells cluster in the
      centre of neurospheres, and demonstrate the use of MBs for the spatial
      localization of specific gene-expressing cells within heterogeneous cell
      populations. 

PMID- 24013404
TI  - Graphical assessment of consistency in treatment effect among countries in multi
      regional clinical trials.
AB  - BACKGROUND: One key objective of a multi-regional clinical trial (MRCT) is to use
      the trial results to 'bridge' from the global level to local region in support of
      local registrations. However, data from each individual country are typically
      limited and the large number of countries will increase the chance of false
      positive findings. PURPOSE: Graphical tools to facilitate identification of
      potential outlying countries could be useful for country-level assessment.
      Existing methods such as funnel plot and expected range of treatment effect can
      substantially increase the false positive rate. The expected range approach can
      also have a very low power when there are a large number of small countries,
      which is typical in a MRCT. METHODS: In this article, we apply normal probability
      plots, commonly used as a diagnostic tool in linear regression analysis, to
      assess the differences among countries. Evidence of possible inconsistency, which
      incorporates both the estimated treatment effect and sample size, is plotted
      against its expected order statistic. RESULTS: A simulation study is conducted to
      assess the impact of the negative correlation among residuals due to unequal
      sample sizes among countries and the performance of the proposed methods compared
      to existing approaches. The proposed methods tend to have a balanced
      consideration with substantially smaller false positive rate and reasonable
      probability to identify outlying countries in realistic scenarios. LIMITATIONS:
      While much lower than that of commonly used methods, the false positive rates of
      the proposed methods are not strictly controlled. This may be acceptable for
      these graphical tools with intention to flag potential outliers for
      investigation. CONCLUSIONS: We recommend routine use of normal probability plots
      in MRCTs as a tool to identify potential outliers. If the normal probability plot
      is approximately linear but has heavy tails with a few outlying countries, these
      potential outliers should be examined carefully to understand the possible
      reasons.

PMID- 24013405
TI  - Assessment of biomarkers for risk prediction with nested case-control studies.
AB  - BACKGROUND: Accurate risk prediction plays a key role in disease prevention and
      disease management; emergence of new biomarkers may lead to an important question
      about how much improvement in prediction accuracy it would achieve by adding the
      new markers into the existing risk prediction tools. PURPOSE: In large
      prospective cohort studies, the standard full-cohort design, requiring marker
      measurement on the entire cohort, may be infeasible due to cost and low rate of
      the clinical condition of interest. To overcome such difficulties, nested case
      control (NCC) studies provide cost-effective alternatives but bring about
      challenges in statistical analyses due to complex data sets generated. METHODS:
      To evaluate prognostic accuracy of a risk model, Cai and Zheng proposed a class
      of nonparametric inverse probability weighting (IPW) estimators for accuracy
      measures in the time-dependent receiver operating characteristic curve analysis.
      To accommodate a three-phase NCC design in Nurses' Health Study, we extend the
      double IPW estimators of Cai and Zheng to develop risk prediction models under
      time-dependent generalized linear models and evaluate the incremental values of
      new biomarkers and genetic markers. RESULTS: Our results suggest that aggregating
      the information from both the genetic markers and biomarkers substantially
      improves the accuracy for predicting 5-year and 10-year risks of rheumatoid
      arthritis. CONCLUSIONS: Our method provided robust procedures to evaluate the
      incremental value of new biomarkers allowing for complex sampling designs.

PMID- 24013406
TI  - Synthesis, evaluation of antioxidant activity and crystal structure of 2,4
      dimethylbenzoylhydrazones.
AB  - 2,4-Dimethylbenzoylhydrazones 1-30 were synthesized by condensation reactions of
      2,4-dimethylbenzoylhydrazide with various aromatic aldehydes and characterized.
      The assigned structures of compounds 10, 15 and 22 were further supported by
      single-crystal X-ray diffraction data. The synthesized compounds were evaluated
      for their in vitro DPPH radical scavenging activity. They exerted varying degree
      of scavenging activity toward DPPH radical with IC50 values between 25.6-190 uM.
      Compounds 1, 4, 2, 3, 7, and 6 have IC50 values of 25.6, 28.1, 29.3, 29.8, 30.0
      and 30.1 uM respectively, showing better activity than an n-propyl gallate
      standard (IC50 value = 30.30 uM). For super oxide anion scavenging activity
      compounds 1, 2 and 3 with IC50 values of 98.3, 102.6, and 105.6, respectively,
      also showed better activity than the n-propyl gallate standard (IC50 value =
      106.34 uM).

PMID- 24013407
TI  - Identification of compounds from the water soluble extract of Cinnamomum cassia
      barks and their inhibitory effects against high-glucose-induced mesangial cells.
AB  - The difficulty of diabetic nephropathy (DN) treatment makes prevention the best
      choice. Cinnamomum cassia barks, known as Chinese cinnamon or Chinese cassia, is
      one of the most popular natural spices and flavoring agents in many parts of the
      World. Since previous reports indicated that Chinese cinnamon extract could be
      used for the treatment of diabetes, we proposed that this spice may be beneficial
      for the prevention of DN. However, the responsible compounds need to be further
      identified. In this study, we isolated three new phenolic glycosides,
      cinnacassosides A-C (1-3), together with fifteen known compounds from the water
      soluble extract of Chinese cinnamon. The structures of the new compounds were
      identified by comprehensive spectroscopic evidence. Eleven compounds (6-9, 11, 13
      18) were isolated from this spice for the first time, despite extensive research
      on this species in the past, which added new facets for the chemical profiling of
      this spice. These isolates were purposely evaluated for their inhibitory effects
      on IL-6 and extracellular matrix production in mesangial cells which are
      definitely implicated in DN. The results showed that compounds 4-8 could inhibit
      over secretion of IL-6, collagen IV and fibronectin against high-glucose-induced
      mesangial cells at 10 mM, suggesting that Chinese cinnamon could be used as a
      functional food against DN. 

PMID- 24013408
TI  - Chaetochromones A and B, two new polyketides from the fungus Chaetomium indicum
      (CBS.860.68).
AB  - Chaetochromones A (1) and B (2), two novel polyketides, were isolated from the
      crude extract of fungus Chaetomium indicum (CBS.860.68) together with three known
      analogues PI-3(3), PI-4 (4) and SB236050 (5). The structures of these compounds
      were determined by HRESI-MS and NMR experiments. Chaetochromones A (1) and B (2)
      are a member of the polyketides family, which might originate from a similar
      biogenetic pathway as the known compounds PI-3 (3), PI-4 (4) and SB236050 (5).
      The biological activities of these secondary metabolites were evaluated against
      eight plant pathogens, including Alternaria alternata, Ilyonectria radicicola,
      Trichoderma viride pers, Aspergillus niger, Fusarium verticillioide, Irpex
      lacteus (Fr.), Poria placenta (Fr.) Cooke and Coriolus versicolor (L.) Quel.
      Compound 1 displayed moderate inhibitory rate (>60%) against the brown rot fungus
      Poria placenta (Fr.) Cooke, which causes significant wood decay. In addition, the
      cytotoxic activities against three cancer cell lines A549, MDA-MB-231, PANC-1
      were also tested, without any inhibitory activities being detected. 

PMID- 24013409
TI  - Physiological roles and potential therapeutic applications of the P2X7 receptor
      in inflammation and pain.
AB  - The P2X7 receptor (P2X7R) is a nonselective cation channel that is activated by
      extracellular ATP and triggers the secretion of several proinflammatory
      substances, such as IL-1beta, IL-18, TNF-alpha, and nitric oxide. Recently,
      several preclinical studies have demonstrated that this receptor participates in
      inflammation and pain mechanisms. Taken together, these results indicate that
      P2X7R is a promising pharmacological target, and compounds that modulate the
      function of this receptor show potential as new anti-inflammatory medicines. In
      this review, we discuss aspects of P2X7R pharmacology and the participation of
      this protein in inflammation and pain and provide an overview of some promising
      compounds that have been tested as antagonists of P2X7R, with clinical
      applicability. 

PMID- 24013410
TI  - Impact of organic and inorganic fertilizers application on the phytochemical and
      antioxidant activity of Kacip Fatimah (Labisia pumila Benth).
AB  - A study was conducted to compare secondary metabolites and antioxidant activity
      of Labisia pumila Benth (Kacip Fatimah) in response to two sources of fertilizer
      [i.e., organic (chicken dung; 10% N:10% P2O5:10% K2O) and inorganic fertilizer
      (NPK green; 15% N, 15% P2O5, 15% K2O)] under different N rates of 0, 90, 180 and
      270 kg N/ha. The experiment was arranged in a randomized complete block design
      replicated three times. At the end of 15 weeks, it was observed that the
      application of organic fertilizer enhanced the production of total phenolics,
      flavonoids, ascorbic acid, saponin and gluthathione content in L. pumila,
      compared to the use of inorganic fertilizer. The nitrate content was also reduced
      under organic fertilization. The application of nitrogen at 90 kg N/ha improved
      the production of secondary metabolites in Labisia pumila. Higher rates in excess
      of 90 kg N/ha reduced the level of secondary metabolites and antioxidant activity
      of this herb. The DPPH and FRAP activity was also highest at 90 kg N/ha. The
      results indicated that the use of chicken dung can enhance the production of
      secondary metabolites and improve antioxidant activity of this herb.

PMID- 24013411
TI  - Design, synthesis and structure-activity relationship of novel quinoxaline
      derivatives as cancer chemopreventive agent by inhibition of tyrosine kinase
      receptor.
AB  - The cancer chemopreventive activity of quinoxaline derivatives 1-20 has been
      evaluated by studying the inhibitory effect on Epstein-Barr virus early antigen
      (EBV-EA) activation. The quinoxaline derivatives 1-20 showed inhibitory effect on
      EBV-EA activation without cytotoxicity on Raji cells. All compounds exhibited
      dose dependent inhibitory activities, most of them showed significant activity at
      1000 mol ratio/12-O-tetradecanoylphorbol-13-acetate (TPA). Compounds 7 and 9
      exhibited stronger inhibitory effects on the EBV-EA activation than that of the
      representative control, oleanolic acid, at the highest measured concentration. In
      addition, compounds 7-10 showed potent and selective inhibition of human tyrosine
      kinase (TRK) in liver cancer HepG2 and breast cancer MCF-7 cell lines similar to
      the positive control, doxorubicin.

PMID- 24013412
TI  - Identification and characterization of novel indole based small molecules as
      anticancer agents through SIRT1 inhibition.
AB  - In our pursuit to develop new potential anticancer leads, we designed a
      combination of structural units of indole and substituted triazole; and a library
      of 1-{1-methyl-2-[4-phenyl-5-(propan-2-ylsulfanyl)-4H-1,2,4-triazol-3-yl]-1H
      indol-3-yl}methanamine derivatives was synthesized and characterized. Cytotoxic
      evaluations of these molecules over a panel of three human cancer cell lines were
      carried out. Few molecules exhibited potent growth inhibitory action against the
      treated cancer cell lines at lower micro molar concentration. An in vitro assay
      investigation of these active compounds using recombinant human SIRT1 enzyme
      showed that one of the compounds (IT-14) inhibited the deacetylation activity of
      the enzyme. The in vivo study of IT-14 exemplified its promising action by
      reducing the prostate weight to the body weight ratio in prostate hyperplasia
      animal models. A remarkable decrease in the disruption of histoarchitecture of
      the prostate tissues isolated from IT-14 treated animal compared to that of the
      positive control was observed. The molecular interactions with SIRT1 enzyme were
      also supported by molecular docking simulations. Hence this compound can act as a
      lead molecule to treat prostatic hyperplasia.

PMID- 24013413
TI  - 3-(3-Butylamino-2-hydroxy-propoxy)-1-hydroxy-xanthen-9-one acts as a
      topoisomerase IIalpha catalytic inhibitor with low DNA damage.
AB  - As a continuous study we prepared several alkylamine (n = 3-6) and evaluated for
      the pharmacological activity and mode of action. In the topoisomerase IIalpha
      (topo IIalpha) inhibition test, compound 4 showed strongest inhibitory activity
      among the compounds at 10 MUM. Inhibitory activities of the compounds are in the
      order of 4 (n = 4) > 1 (n = 3) >> 5 (n = 5) ~ 6 (n = 6); 8 (n = 4) >> 7 (n = 3) ~
      9 (n = 5) ~ 10 (n = 6) where n is the number of carbon in the aliphatic side
      chain in ring C and compounds 7-10 have additional methoxy group in ring A
      compared to compounds 1, 4-6. Compound 4 showed efficient cytotoxicities against
      T47D (IC50: 0.93 +/- 0.04 MUM) and HCT15 (IC50: 0.78 +/- 0.01 MUM) cells, which
      are higher than etoposide. Compound 4 was also an ATP-competitive human topo
      IIalpha catalytic inhibitor with partially blocking human topo IIalpha-catalyzed
      ATP hydrolysis and intercalating into DNA. Compound 4 induced much less DNA
      damage than etoposide in HCT15 human colorectal carcinoma cells. Overall,
      compound 4 can be a potential anticancer agent acting as topo IIalpha catalytic
      inhibitor with low DNA damage.

PMID- 24013414
TI  - Synthesis and allosteric modulation of the dopamine receptor by peptide analogs
      of L-prolyl-L-leucyl-glycinamide (PLG) modified in the L-proline or L-proline and
      L-leucine scaffolds.
AB  - Novel analogs of L-prolyl-L-leucylglycinamide (PLG) were synthesized wherein the
      prolyl residue was replaced with other amino acids based on a 3,5-disubstituted
      proline scaffold. In some examples, the L-leucyl residue was also replaced by L
      valine. These analogs were tested for their ability to enhance the binding of
      [(3)H]-N-propylnorapomorphine to short isoform of human dopamine D2 receptors.
      Compounds 18b and 19b, increased [(3)H] NPA binding at concentrations between 10(
      12) and 10(-9) M, which is similar to the effect of PLG in this assay and,
      provides evidences that these compounds are acting as allosteric modulators of
      dopamine D2 receptors.

PMID- 24013415
TI  - Synthesis and biological evaluation of phenyl substituted polyoxygenated xanthone
      derivatives as anti-hepatoma agents.
AB  - A series of novel derivatives of phenyl substituted tetramethoxy xanthone were
      synthesized and evaluated for their in vitro cytotoxicity against human
      hepatocellular carcinoma (HCC) and non-tumor hepatic cells. Among these
      derivatives, compound 6 was more potent than positive control 5-fluorouracil (5
      Fu) on QGY-7703 and SMMC-7721 cells with IC50 values of 6.27 MUM, 7.50 MUM and
      15.56 MUM, 14.55 MUM, respectively. Furthermore, compounds 6, 14, 16, and 29
      exhibited much better selectivity toward the normal hepatic cell line QSG-7701
      than 5-Fu. Additionally, compound 6 significantly induced cell apoptosis in QGY
      7703 cells. Our findings suggested that these phenylxanthone derivatives may hold
      promise as chemotherapeutic agents for the treatment of human HCC.

PMID- 24013416
TI  - An evolving tail of centromere histone variant CENP-A.

PMID- 24013417
TI  - Participation of mitochondrial fission during mitophagy.

PMID- 24013418
TI  - The protracted maturation of human ESC-derived interneurons.

PMID- 24013419
TI  - Activation of an unusual G-protein in the simple protist Trichomonas vaginalis.

PMID- 24013420
TI  - Switching roles for a helicase.

PMID- 24013421
TI  - Ubp-M serine 552 phosphorylation by cyclin-dependent kinase 1 regulates cell
      cycle progression.
AB  - In eukaryotic cells, genomic DNA is organized into a chromatin structure, which
      not only serves as the template for DNA-based nuclear processes, but also as a
      platform integrating intracellular and extracellular signals. Although much
      effort has been spent to characterize chromatin modifying/remodeling activities,
      little is known about cell signaling pathways targeting these chromatin
      modulators. Here, we report that cyclin-dependent kinase 1 (CDK1) phosphorylates
      the histone H2A deubiquitinase Ubp-M at serine 552 (S552P), and, importantly,
      this phosphorylation is required for cell cycle progression. Mass spectrometry
      analysis confirmed Ubp-M is phosphorylated at serine 552, and in vitro and in
      vivo assays demonstrated that CDK1/cyclin B kinase is responsible for Ubp-M
      S552P. Interestingly, Ubp-M S552P is not required for Ubp-M tetramer formation,
      deubiquitination activity, substrate specificity, or regulation of gene
      expression. However, Ubp-M S552P is required for cell proliferation and cell
      cycle G 2/M phase progression. Ubp-M S552P reduces Ubp-M interaction with nuclear
      export protein CRM1 and facilitates Ubp-M nuclear localization. Therefore, these
      studies confirm that Ubp-M is phosphorylated at S552 and identify CDK1 as the
      enzyme responsible for the phosphorylation. Importantly, this study specifically
      links Ubp-M S552P to cell cycle G 2/M phase progression.

PMID- 24013422
TI  - Measurement and modeling of transcriptional noise in the cell cycle regulatory
      network.
AB  - Fifty years of genetic and molecular experiments have revealed a wealth of
      molecular interactions involved in the control of cell division. In light of the
      complexity of this control system, mathematical modeling has proved useful in
      analyzing biochemical hypotheses that can be tested experimentally. Stochastic
      modeling has been especially useful in understanding the intrinsic variability of
      cell cycle events, but stochastic modeling has been hampered by a lack of
      reliable data on the absolute numbers of mRNA molecules per cell for cell cycle
      control genes. To fill this void, we used fluorescence in situ hybridization
      (FISH) to collect single molecule mRNA data for 16 cell cycle regulators in
      budding yeast, Saccharomyces cerevisiae. From statistical distributions of single
      cell mRNA counts, we are able to extract the periodicity, timing, and magnitude
      of transcript abundance during the cell cycle. We used these parameters to
      improve a stochastic model of the cell cycle to better reflect the variability of
      molecular and phenotypic data on cell cycle progression in budding yeast. 

PMID- 24013423
TI  - Recruitment into stress granules prevents irreversible aggregation of FUS protein
      mislocalized to the cytoplasm.
AB  - Fused in sarcoma (FUS) belongs to the group of RNA-binding proteins implicated as
      underlying factors in amyotrophic lateral sclerosis (ALS) and certain other
      neurodegenerative diseases. Multiple FUS gene mutations have been linked to
      hereditary forms, and aggregation of FUS protein is believed to play an important
      role in pathogenesis of these diseases. In cultured cells, FUS variants with
      disease-associated amino acid substitutions or short deletions affecting nuclear
      localization signal (NLS) and causing cytoplasmic mislocalization can be
      sequestered into stress granules (SGs). We demonstrated that disruption of motifs
      responsible for RNA recognition and binding not only prevents SG recruitment, but
      also dramatically increases the protein propensity to aggregate in the cell
      cytoplasm with formation of juxtanuclear structures displaying typical features
      of aggresomes. Functional RNA-binding domains from TAR DNA-binding protein of 43
      kDa (TDP-43) fused to highly aggregation-prone C-terminally truncated FUS protein
      restored the ability to enter SGs and prevented aggregation of the chimeric
      protein. Truncated FUS was also able to trap endogenous FUS molecules in the
      cytoplasmic aggregates. Our data indicate that RNA binding and recruitment to SGs
      protect cytoplasmic FUS from aggregation, and loss of this protection may trigger
      its pathological aggregation in vivo. 

PMID- 24013424
TI  - CD147 regulates the expression of MCT1 and lactate export in multiple myeloma
      cells.
AB  - Increased use of the glycolytic pathway, even in the presence of oxygen, has
      recently been recognized as a key characteristic of malignant cells. However, the
      glycolytic phenotype results in increased lactic acid production and, in order to
      prevent cellular acidosis, tumor cells must increase proton efflux via
      upregulation of pH regulators such as proton-pumps, sodium-proton exchangers,
      and/or monocarboxylate transporters (MCT) (e.g., MCT1, MCT4). Interestingly,
      expression of MCT1 and MCT4 has been previously shown to be dependent upon
      expression of the transmembrane glycoprotein CD147. Recently, we demonstrated
      that primary patient multiple myeloma (MM) cells and human MM cell lines (HMCLs)
      overexpress CD147. Therefore, the goal of the current study was to specifically
      determine if MCT1 and MCT4 were also overexpressed in MM cells. RT-PCR analysis
      demonstrated both primary patient MM cells and HMCLs overexpress MCT1 and MCT4
      mRNA. Notably, primary MM cells or HMCLs were found to express variable levels of
      MCT1 and/or MCT4 at the protein level despite CD147 expression. In those HMCLs
      positive for MCT1 and/or MCT4 protein expression, MCT1 and/or MCT4 were found to
      be associated with CD147. Specific siRNA-mediated downregulation of MCT1 but not
      MCT4 resulted in decreased HMCL proliferation, decreased lactate export, and
      increased cellular media pH. However, western blot analysis revealed that
      downregulation of MCT1 also downregulated CD147 and vice versa despite no effect
      on mRNA levels. Taken together, these data demonstrate the association between
      MCT1 and CD147 proteins in MM cells and importance of their association for
      lactate export and proliferation in MM cells.

PMID- 24013425
TI  - Modification of Akt by SUMO conjugation regulates alternative splicing and cell
      cycle.
AB  - Akt/PKB is a key signaling molecule in higher eukaryotes and a crucial protein
      kinase in human health and disease. Phosphorylation, acetylation, and
      ubiquitylation have been reported as important regulatory post-translational
      modifications of this kinase. We describe here that Akt is modified by SUMO
      conjugation, and show that lysine residues 276 and 301 are the major SUMO
      attachment sites within this protein. We found that phosphorylation and
      SUMOylation of Akt appear as independent events. However, decreasing Akt
      SUMOylation levels severely affects the role of this kinase as a regulator of
      fibronectin and Bcl-x alternative splicing. Moreover, we observed that the Akt
      mutant (Akt E17K) found in several human tumors displays increased levels of
      SUMOylation and also an enhanced capacity to regulate fibronectin splicing
      patterns. This splicing regulatory activity is completely abolished by decreasing
      Akt E17K SUMO conjugation levels. Additionally, we found that SUMOylation
      controls Akt regulatory function at G1/S transition during cell cycle
      progression. These findings reveal SUMO conjugation as a novel level of
      regulation for Akt activity, opening new areas of exploration related to the
      molecular mechanisms involved in the diverse cellular functions of this kinase.

PMID- 24013426
TI  - Nuclear PKM2 regulates the Warburg effect.
AB  - Pyruvate kinase is a rate-limiting glycolytic enzyme. The PKM1 and PKM2 isoforms
      result from mutually exclusive alternative splicing of the PKM pre-mRNA. PKM2
      rather than PKM1 regulates the Warburg effect and tumorigenesis by poorly
      understood mechanisms. Emerging evidence has revealed that ERK1/2 phosphorylates
      PKM2, but not PKM1, leading to PIN1-dependent cis-trans isomerization and
      conversion of PKM2 from a tetramer to a monomer. Monomeric PKM2 translocates into
      the nucleus, where it functions as a histone kinase and upregulates the
      expression of c-Myc and cyclin D1, thereby promoting the Warburg effect and cell
      cycle progression, respectively. Thus, nuclear PKM2 is essential for
      tumorigenesis and may serve as a target for treating human cancer.

PMID- 24013427
TI  - Wee1 kinase as a target for cancer therapy.
AB  - Wee1, a protein kinase, regulates the G 2 checkpoint in response to DNA damage.
      Preclinical studies have elucidated the role of wee1 in DNA damage repair and the
      stabilization of replication forks, supporting the validity of wee1 inhibition as
      a viable therapeutic target in cancer. MK-1775, a selective and potent small
      molecule inhibitor of wee1, is under clinical development as a potentiator of DNA
      damage caused by cytotoxic chemotherapies. We present a review of the role of
      wee1 in the cell cycle and DNA replication and summarize the clinical development
      to date of this novel class of anticancer agents.

PMID- 24013430
TI  - eNOSI4 and EPHX1 polymorphisms affect maternal susceptibility to preeclampsia:
      analysis of five polymorphisms predisposing to cardiovascular disease in 279
      Caucasian and 241 African women.
AB  - PURPOSE: The aim of this study was to evaluate possible associations of genetic
      polymorphisms predisposing to cardiovascular disease with the development and/or
      the severity of preeclampsia. METHODS: A two hospital-based prospective case
      control study was performed in Germany and Ghana. 470 blood samples of 250
      Caucasian and 220 black African have been genotyped by pyrosequencing and
      fragment length analysis. We evaluated the distribution of the epoxide hydrolase
      1 (EPHX1) polymorphism on exon 3, the endothelial nitric oxide synthase (eNOS)
      polymorphisms on exon 7 and on intron 4, the angiotensinogen polymorphism on exon
      2 and the estrogen receptor 1 polymorphism in intron 1. RESULTS: 74 Caucasian and
      84 African were classified as preeclampsia with 27 Caucasian developing a
      hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome and 17
      African women experiencing eclampsia. Multivariate logistic regression analysis
      adjusting for ethnicity, age and parity revealed for carriers of eNOSI4 VNTR4a a
      1.7-fold increased (95% CI 1.10-2.711, p = 0.016) risk to develop preeclampsia
      and a 3.6-fold increase for carriers of the EPHX1 113Tyr (95% CI 1.366-8.750, p =
      0.009) to develop severest preeclampsia. CONCLUSION: Our finding of eNOSI4
      polymorphism predisposing to preeclampsia independently of ethnicity, age and
      parity supports the concept of NO being involved in the endothelial disorder
      preeclampsia. Since EPHX1 is highly expressed in the liver, can interact with
      various signaling pathways and is involved in central nervous system disorders,
      the association of EPHX1 polymorphism with the HELLP syndrome and eclampsia may
      hint to EPHX being a further key player in the pathogenesis of preeclampsia.

PMID- 24013429
TI  - Changing T-cell enigma: cancer killing or cancer control?
AB  - Data from different laboratories and theoretical considerations challenge our
      current view on anticancer immunity. Immune cells are capable of destroying
      cancer cells under in vitro and in vivo conditions. Therefore, cellular immunity
      is considered to control cancers through mechanisms that kill cancers. Yet,
      therapeutic anticancer immune responses rarely delete cancers. If efficient, they
      rather establish a life with stable disease. This raises the question of whether
      killing is the sole mechanism by which immune therapy attacks cancers. Here, we
      show that, besides cancer eradication by cytotoxic lymphocytes, other modes of
      action are operative and strictly required for cancer control. We show that T
      helper-1 cells arrest cancer growth by driving cancers into a state of stable or
      permanent growth arrest, called senescence. Such immune cells establish cytokine
      producing walls around developing cancers. When producing interferon-gamma and
      tumor necrosis factor, this cytokine-induced tumor immune-surveillance keeps the
      cancer cells in a permanently non-proliferating state. Simultaneously,
      antiangiogenic chemokines cut their connections to the surrounding tissues. This
      strategy significantly reduces tumor burden and prolongs life of cancer-bearing
      animals. As human cancers also undergo senescence, the current data suggest tumor
      immune surveillance through cytokine-induced senescence, instead of tumor
      eradication, as the more realistic and primary goal of cancer control. 

PMID- 24013428
TI  - Clamping down on mammalian meiosis.
AB  - The RAD9A-RAD1-HUS1 (9-1-1) complex is a PCNA-like heterotrimeric clamp that
      binds damaged DNA to promote cell cycle checkpoint signaling and DNA repair.
      While various 9-1-1 functions in mammalian somatic cells have been established,
      mounting evidence from lower eukaryotes predicts critical roles in meiotic germ
      cells as well. This was investigated in 2 recent studies in which the 9-1-1
      complex was disrupted specifically in the mouse male germline through conditional
      deletion of Rad9a or Hus1. Loss of these clamp subunits led to severely impaired
      fertility and meiotic defects, including faulty DNA double-strand break repair.
      While 9-1-1 is critical for ATR kinase activation in somatic cells, these studies
      did not reveal major defects in ATR checkpoint pathway signaling in meiotic
      cells. Intriguingly, this new work identified separable roles for 9-1-1 subunits,
      namely RAD9A- and HUS1-independent roles for RAD1. Based on these studies and the
      high-level expression of the paralogous proteins RAD9B and HUS1B in testis, we
      propose a model in which multiple alternative 9-1-1 clamps function during
      mammalian meiosis to ensure genome maintenance in the germline.

PMID- 24013431
TI  - Expression and significance of biglycan in endometrial cancer.
AB  - OBJECTIVE: This study aimed to determine the expression level of biglycan in
      different lesion properties of endometrium and to investigate the possible
      function and prognostic value of biglycan in endometrial cancer. METHODS:
      Immunohistochemical staining (IHC) and quantitative realtime reverse
      transcription polymerase chain reaction (qRT-PCR) were used to determine the
      protein and mRNA levels of biglycan in human normal endometrium, atypical
      hyperplasia endometrium, and endometrial cancer tissue samples. The expression of
      biglycan in serum and peritoneal washings was detected by ELISA method. Then we
      analyzed the correlation of biglycan expression with clinicopathological
      parameters in endometrial cancer. RESULTS: (1) Biglycan was overexpressed in
      endometrial cancer, especially in cancerous mesenchyme. Moreover, biglycan
      expression was significantly correlated with histopathological grade and FIGO
      stage of endometrial cancer; (2) Biglycan expression level in sera and peritoneal
      washings was significantly higher in endometrial cancer patients; otherwise,
      Serum expression correlated with clinicopathological parameters of endometrial
      cancer; (3) Higher level expression of biglycan in cancerous mesenchyme
      correlated with poor prognosis of endometrial cancer. CONCLUSIONS: Biglycan might
      play a role in the progression of human endometrial cancer and it might be a
      useful molecular marker for the prognosis of endometrial cancer. This research is
      an initial step towards biglycan as a potential prognosis marker in endometrial
      cancer.

PMID- 24013432
TI  - Message from the Editor-in-Chief.

PMID- 24013433
TI  - Myomectomy during caesarean: a retrospective evaluation of 16 cases.
AB  - AIM: To evaluate the results and complications of myomectomy carried out during
      caesarean section. MATERIALS AND METHOD: A retrospective study of 16 patients who
      underwent myomectomy concurrently with caesarean section in our clinic between
      January 2009 and September 2012 was conducted. The pre- and postoperative
      haemoglobin values, number, size and total volume of excised fibroid nodules,
      location of fibroids, duration of operation, and duration of hospital stay of all
      patients were retrospectively investigated. RESULTS: While the most common
      leiomyoma was transmural myoma, with ten cases encountered, the most common
      location was in the corpus anterior, where transmural myomas were seen in five
      patients. The volume of the excised leiomyomata ranged from 84 to 3.300 cm3. The
      average preoperative haemoglobin value of our patients was 11.4 g/dl, while the
      postoperative value was 10.3 g/dl. Of 16 patients included in the study, two
      required blood transfusions due to excessive bleeding. Uterine defects caused by
      the myomectomy were closed without problems in all patients, and no patient
      required a hysterectomy. The average time for the myomectomy and caesarean
      section procedure was 56.1 min. All patients were discharged without problems an
      average of 3.25 days after the operation. CONCLUSION: Myomectomy carried out
      during caesarean section is a trusted surgical intervention regardless of the
      size of leiomyomata.

PMID- 24013434
TI  - Efficient cyanoaromatic photosensitizers for singlet oxygen production: synthesis
      and characterization of the transient reactive species.
AB  - In order to graft cyanoaromatic molecules onto various inert supports, we
      designed two new cyanoanthracene derivatives of benzo[b]triphenylene-9,14
      dicarbonitrile (DBTP, 1), which already demonstrated good photosensitizing
      properties. We synthesized 3-(N-hydroxypropyl)carboxamido-9,14
      dicyanobenzo[b]triphenylene, 3 and 3-(N-N0-Boc-aminohexyl)carboxamido-9,14
      dicyanobenzo[b]triphenylene, 4 and compared their photophysical properties in
      acetonitrile relative to those of the parent compound 1 and its carboxylic
      derivative 9,14-dicyanobenzo[b]triphenylene-3-carboxylic acid, 2. The transient
      species were analysed and the quantum yields of singlet oxygen production
      (PhiDelta) determined in acetonitrile. The effect of chemical functionalization
      can be considered negligible, since absorption spectra, fluorescence emission
      spectra and fluorescence lifetimes do not significantly change with the
      substituent. The triplet-triplet absorption spectra and the triplet excited state
      lifetimes are similar for the whole series. For compounds 1-4 high values of
      PhiDelta, close to that of the standard sensitizer 1H-phenalen-1-one (PN,
      PhiDelta ~ 1), and higher than that of the well-known photosensitizer 9,10
      dicyanoanthracene (DCA), are due to very efficient intersystem crossing from the
      singlet to the triplet excited state and subsequent energy transfer to ground
      state oxygen ((3)O2). They belong to a class of very efficient photosensitizers,
      absorbing visible light and stable under irradiation, they may be functionalized
      without significant changes to their photophysical behaviour, and grafted onto
      various supports.

PMID- 24013435
TI  - Do cardiac children need more red blood cell transfusions than other critically
      ill children?

PMID- 24013436
TI  - Partial liberalization of visiting policies and ICU staff: a before-and-after
      study.
AB  - PURPOSE: To investigate possible psychological distress among staff after partial
      liberalization of visiting policies in intensive care units (ICUs). METHODS: We
      surveyed eight Italian ICUs planning to increase daily visiting to at least 8 h.
      Participants completed the Maslach-Jackson Burnout Inventory and the State-Trait
      Anxiety Inventory before policy change (T0), after 6 months (T1) and 12 months
      (T2). At T0 and T2, their opinions on the new policy were solicited. Analyses
      were adjusted for main known confounders (age, gender, centre, educational and
      marital status, experience in ICU, baseline level of burnout or anxiety, and
      mortality rate). RESULTS: Baseline response rate was 89 % (230/258); 198 subjects
      (77 %) responded at T0 and T2, whereas 184 (71 %) participated in all three
      phases. High burnout levels were identified in 34.5 % of participants at T0 and
      42.6 % at T2 (adjusted p = 0.001). All three phases showed a predominance of high
      burnout among nurses (adjusted p = 0.002). State and trait anxiety scores
      remained stable (adjusted p = 0.100 and 0.288, respectively). Most participants
      viewed the change positively at T0 (doctors 81.7 %; nurses 67.7 %) and T2
      (doctors 87.0 %; nurses 62.7 %). At T2, 129 participants made comments (180
      positive, 136 negative). Subjects with high burnout were more likely to comment
      negatively (p = 0.011). CONCLUSIONS: Partial liberalization of ICU visiting
      policies was associated over the course of a year with a small but significant
      increase in staff members' burnout levels. Nonetheless, doctors and nurses viewed
      the policy positively, maintaining this opinion after 1 year. Negative views were
      strongly correlated with burnout.

PMID- 24013437
TI  - Ultrasound-guided central venous catheter insertion: teaching and learning.

PMID- 24013438
TI  - Magnetic resonance mapping of the rim of articular cartilage defects of the
      patella.
AB  - PURPOSE: Elevated T2-values of articular cartilage are associated with an
      increase in cartilage water that results from a damaged collagen matrix, and
      provide a marker for cartilage damage. We used T2 mapping to analyse the rim of
      cartilage defects that appeared to be intact on the morphological sequences, to
      determine whether there are early biochemical changes already present. METHOD: We
      calculated T2 values for the rim of cartilage defects in 25 patients and compared
      these values to another area of control cartilage in these patients. RESULTS: A
      highly significant increase in T2 values of the deep, superficial, and global
      layer of the rim versus the control cartilage was measured. ANOVA showed a
      significant correlation of the defect levels with the T2 values of the deep and
      global zone of the adjacent cartilage tissue, but not with the superficial zone.
      CONCLUSION: Although cartilage appears to be intact on morphological sequences,
      T2 mapping can show a loss of structural anisotropy of collagen and the
      associated increase in cartilage water that indicates the destruction of the
      adjacent cartilage. Preoperative information about the degree of damage of the
      collagen matrix will support decision making for cartilage repair.

PMID- 24013439
TI  - A microbial profiling method for the human microbiota using high-throughput
      sequencing.
AB  - Study of the human microbiota in relation to human health and disease is a
      rapidly expanding field. To fully understand the complex relationship between the
      human gut microbiota and disease risks, study designs that capture the variation
      within and between human subjects at the population level are required, but this
      has been hampered by the lack of cost-effective methods to characterize this
      variation. Illumina sequencing is inexpensive and produces millions of reads per
      run, but it is unclear whether short reads can adequately represent the microbial
      community of a human host. In this study, we examined the utility of a profiling
      method, microbial nucleotide signatures (MNS), focused on low-depth sampling of
      the human microbiota using Ilumina short reads. This method is intended to aid in
      human population-based studies where large sample sizes are required to
      adequately capture variation in disease or phenotype differences. We found that,
      by calculating the nucleotide diversities along the sequenced 16S rRNA gene
      region, which did not require assembly or phylogenetic identification, we were
      able to differentiate the gut microbial nucleotide signatures of 9 healthy
      individuals. When we further subsampled the reads down to 40,000 reads (51 bp
      long) per sample, the diversity profiles were relatively unchanged. Applying MNS
      to a public datasets showed that it could differentiate body site differences.
      The scalability of our approach offers rapid classification of study participants
      for studies with the sample sizes required for epidemiological studies. Using MNS
      to classify the microbiome associated with a disease state followed by targeted
      in-depth sequencing will give a comprehensive understanding of the role of the
      microbiome in human health.

PMID- 24013440
TI  - Influence of doped nitrogen and vacancy defects on the thermal conductivity of
      graphene nanoribbons.
AB  - A systematic investigation of the thermal conductivity of zigzag graphene
      nanoribbons (ZGNRs) doped with nitrogen and containing a vacancy defect was
      performed using reverse nonequilibrium molecular dynamics (RNEMD). The
      investigation showed that the thermal conductivity of the ZGNRs was significantly
      reduced by nitrogen doping. The thermal conductivity dropped rapidly when the
      nitrogen doping concentration was low. Also, the presence of a vacancy defect was
      found to significantly decrease the thermal conductivity. Initially, as the
      vacancy moved from the heat sink to the heat source, the phonon frequency and the
      phonon energy increased, and the thermal conductivity decreased. When the
      distance between the vacancy in the ZGNR and the edge of the heat sink reached
      2.214 nm, tunneling began to occur, allowing high-frequency phonons to pass
      through the vacancies and transfer some energy. The curve of the thermal
      conductivity of the ZGNRs versus the vacancy position was found to be pan-shaped,
      with the thermal conductivity of the ZGNRs controlled by the phonon. These
      findings could be useful when attempting to control heat transfer on the
      nanoscale using GNR-based thermal devices.

PMID- 24013442
TI  - Physiology of Lichtheimia ramosa obtained by solid-state bioprocess using fruit
      wastes as substrate.
AB  - Due to the amount of nutrients available in the agroindustrial wastes, these can
      be converted into high added-value products by the action of microorganisms in
      solid-state bioprocesses. The aim of this work was to evaluate the growth
      physiology and lipase production of the fungus Lichtheimia ramosa using the
      following Brazilian savannah fruit wastes as substrates: bocaiuva (Acrocomia
      aculeata), pequi (Caryocar brasiliense), guavira (Campomanesia pubescens),
      araticum (Annona crassiflora) and seriguela (Spondias purpurea). These residues
      were triturated, homogenized, adjusted to pH 5.0 and 60 % moisture, sterilized
      and packaged in plastic tray-type bioreactors before inoculation with 10 % (w/v)
      of L. ramosa pre-culture medium. The cultivations were conducted in a
      bacteriological incubator at 30  degrees C for 40 days. Samples were taken every
      5 days and fungi and bacteria contents, proximate composition and lipase activity
      were evaluated. The maximum fungal counting was observed between 25 and 35 days.
      L. ramosa reached the stationary phase next to 40 days in all substrates.
      Mesophilic and psicrophilic aerobic bacteria were not detected. Protein
      enrichment was obtained for all media, being superior in seriguela residues
      (391.66 %), followed by pequi (160.04 %), araticum (143.31 %), guavira (102.42
      %), and bocaiuva (67.88 %). Lipase production was observed in all cultivated
      media, except in pequi residues that showed decreasing lipase activity. The
      higher production was observed in guavira (1.12 U/g) followed by araticum (0.58
      U/g), seriguela (0.41 U/g) and bocaiuva (0.21 U/g) waste substrates. It was
      concluded that the studied fruit wastes have been successfully utilized as
      substrates for protein enrichment and lipase production with L. ramosa. 

PMID- 24013441
TI  - Human rotavirus vaccine (RIX4414) efficacy in the first two years of life: a
      randomized, placebo-controlled trial in China.
AB  - Rotaviruses (RV) are a major cause of severe gastroenteritis (GE) in children
      aged<5 y. For the first time in China, we assessed the efficacy of two oral doses
      of the human rotavirus vaccine (RIX4414) in infants during the first two years of
      life (113808/NCT01171963). Healthy infants aged 6-16 weeks were randomized (1:1)
      to receive two oral doses of either the RIX4414 vaccine/placebo according to a 0,
      1 month schedule. Vaccine efficacy (VE) against severe RVGE was assessed from two
      weeks post-Dose 2 up until the end of the second RV season and calculated with
      its 95% confidence intervals (CI). The primary efficacy objective was met if the
      lower limit of the 95% CI on VE was >=10%. Unsolicited symptoms reported during
      the 31-d post-vaccination follow-up period and serious adverse events (SAEs)
      reported throughout the study were assessed. Of 3333 enrolled infants, 3148 were
      included in the according-to-protocol efficacy cohort. Over two consecutive RV
      seasons, fewer severe RVGE episodes were reported in the RIX4414 group (n=21) vs.
      the placebo group (n=75). VE against severe RVGE was 72% (95% CI: 54.1-83.6); the
      lower limit of the 95% CI on VE was >10%. The number of unsolicited symptoms and
      SAEs reported was similar between both groups. Thirteen deaths (RIX4414=6;
      placebo=7) occurred during the study. All SAEs and deaths in the RIX4414 group
      were considered unrelated to vaccination. Two oral doses of RIX4414 vaccine
      provided a substantial level of protection against severe RVGE in Chinese
      children during the first two years of life.

PMID- 24013443
TI  - Biodegradation of chestnut shell and lignin-modifying enzymes production by the
      white-rot fungi Dichomitus squalens, Phlebia radiata.
AB  - As a discarded lignocellulosic biomass, chestnut shell is of great potential
      economic value, thus a sustainable strategy is needed and valuable for
      utilization of this resource. Herein, the feasibility of biological processes of
      chestnut shell with Dichomitus squalens, Phlebia radiata and their co-cultivation
      for lignin-modifying enzymes (LMEs) production and biodegradation of this
      lignocellulosic biomass was investigated under submerged cultivation. The
      treatment with D. squalens alone at 12 days gained the highest laccase activity
      (9.42 +/- 0.73 U mg(-1)). Combined with the data of laccase and manganese
      peroxidase, oxalate and H2O2 were found to participate in chestnut shell
      degradation, accompanied by a rapid consumption of reducing sugar. Furthermore,
      specific surface area of chestnut shell was increased by 77.6-114.1 % with the
      selected fungi, and total pore volume was improved by 90.2 % with D. squalens.
      Meanwhile, the surface morphology was observably modified by this fungus.
      Overall, D. squalens was considered as a suitable fungus for degradation of
      chestnut shell and laccase production. The presence of LMEs, H2O2 and oxalate
      provided more understanding for decomposition of chestnut shell by the white-rot
      fungi. 

PMID- 24013444
TI  - A brief perspective on the evolution of plastic electronics--from highly
      conducting polymers to conjugated organic semiconductors.
AB  - This Viewpoint reflects on the work published in J. Chem. Soc., Chem. Commun. in
      1977 by the Nobel Prize winners Shirakawa, MacDiarmid and Heeger. This paper,
      which is one of the most cited ChemComm articles of all time, motivated the rapid
      development of conducting (conjugated) polymers and the birth of plastic
      electronics. 

PMID- 24013445
TI  - Characterisation of platinum-based fuel cell catalyst materials using 195Pt
      wideline solid state NMR.
AB  - This study demonstrates the utility of the novel Field Sweep Fourier Transform
      (FSFT) method for acquiring wideline (195)Pt NMR data from various sized Pt
      nanoparticles, Pt-Sn intermetallics/bimetallics used to catalyse oxidative
      processes in fuel cell applications, and various other related Pt3X alloys (X =
      Al, Sc, Nb, Ti, Hf and Zr) which can facilitate oxygen reduction catalysis. The
      (195)Pt and (119)Sn NMR lineshapes measured from the PtSn intermetallic and Pt3Sn
      bimetallic systems suggest that these are more ordered than other closely related
      bimetallic alloys; this observation is supported by other characterisation
      techniques such as XRD. From these reconstructed spectra the mean number of atoms
      in a Pt nanoparticle can be accurately determined, along with detailed
      information regarding the number of atoms present effectively in each layer from
      the surface. This can be compared with theoretical predictions of the number of
      Pt atoms in these various layers for cubo-octahedral nanoparticles, thereby
      providing an estimate of the particle size. A comparison of the common NMR
      techniques used to acquire wideline data from the I = 1/2 (195)Pt nucleus
      illustrates the advantages of the automated FSFT technique over the Spin Echo
      Height Spectroscopy (SEHS) (or Spin Echo Integration Spectroscopy (SEIS))
      approach that dominates the literature in this area of study. This work also
      presents the first (195)Pt NMR characterisation of novel small Pt13 nanoclusters
      which are diamagnetic and thus devoid of metallic character. This unique system
      provides a direct measure of an isotropic chemical shift for these Pt
      nanoparticles and affords a better basis for determining the actual Knight shift
      when compared to referencing against the primary IUPAC shift standard (1.2 M
      Na2PtCl6(aq)) which has a very different local chemical environment. 

PMID- 24013446
TI  - Joint haemorrhage partly accelerated immobilization-induced synovial adhesions
      and capsular shortening in rats.
AB  - PURPOSE: To elucidate the effects of intra-articular haemorrhage on the joint
      capsule of immobilized knees in rats. METHODS: The unilateral knee joints were
      immobilized using a plastic plate and screws. Sham operated rats had only screws
      inserted. A single injection of fresh autologous blood was given postoperatively
      into the knee joints of the immobilized blood injection (Im-B) and the Sham blood
      injection (Sm-B) groups. Normal saline was administered for the immobilized
      saline injection (Im-S) group. Sagittal sections were prepared from the medial
      midcondylar region of the knee and assessed with histological, histomorphometric,
      and immunohistochemical methods. The range of motion (ROM) was measured, and the
      mechanical property of the capsule was assessed by scanning acoustic microscope.
      RESULTS: Absorption of the injected blood was delayed and made severe adhesions
      in the Im-B group. The length of the synovial membrane in the Im-B group was
      significantly shorter than that of the other groups. The ROM was significantly
      restricted in the Im-B group compared with the other groups. The elasticity of
      the posterior capsule in the Im-B group was significantly lower than that in the
      Sm-B group. Iron deposition was observed in the Im-B and Sm-B groups. Strong
      immunoreactivities of CD68, TGF-beta1, and alpha-SMA were observed in the
      adhesion area of the Im-B group. Joint immobilization with blood injection caused
      severe capsular adhesion and limited range of motion. Immunostaining related to
      fibrosis increased with joint haemorrhage. CONCLUSION: Intra-articular
      haemorrhage with joint immobilization might be an accelerated risk factor for
      joint contracture. It is likely that leaving a haematoma inside an immobilized
      joint should be avoided.

PMID- 24013449
TI  - Thiophenic compounds adsorption on Na(I)Y and rare earth exchanged Y zeolites: a
      density functional theory study.
AB  - We have theoretically investigated the adsorption of thiophene, benzothiophene,
      dibenzothiophene on Na(I)Y and rare earth exchanged La(III)Y, Ce(III)Y, Pr(III)Y
      Nd(III)Y zeolites by density functional theory calculations. The calculated
      results show that except benzothiophene adsorbed on Na(I)Y with a stand
      configuration, the stable adsorption structures of other thiophenic compounds on
      zeolites exhibit lying configurations. Adsorption energies of thiophenic
      compounds on the Na(I)Y are very low, and decrease with the increase of the
      number of benzene rings in thiophenic compounds. All rare earth exchanged
      zeolites exhibit strong interaction with thiophene. La(III)Y and Nd(III)Y
      zeolites are found to show enhanced adsorption energies to benzothiophene and
      Pr(III)Y zeolites are favorable for dibenzothiophene adsorption. The analysis of
      the electronic total charge density and electron orbital overlaps show that the
      thiophenic compounds interact with zeolites by pi-electrons of thiophene ring and
      exchanged metal atom. Mulliken charge populations analysis reveals that
      adsorption energies are strongly dependent on the charge transfer of thiophenic
      molecule and exchanged metal atom.

PMID- 24013448
TI  - Conditioned medium from bone marrow-derived mesenchymal stem cells improves
      recovery after spinal cord injury in rats: an original strategy to avoid cell
      transplantation.
AB  - Spinal cord injury triggers irreversible loss of motor and sensory functions.
      Numerous strategies aiming at repairing the injured spinal cord have been
      studied. Among them, the use of bone marrow-derived mesenchymal stem cells
      (BMSCs) is promising. Indeed, these cells possess interesting properties to
      modulate CNS environment and allow axon regeneration and functional recovery.
      Unfortunately, BMSC survival and differentiation within the host spinal cord
      remain poor, and these cells have been found to have various adverse effects when
      grafted in other pathological contexts. Moreover, paracrine-mediated actions have
      been proposed to explain the beneficial effects of BMSC transplantation after
      spinal cord injury. We thus decided to deliver BMSC-released factors to spinal
      cord injured rats and to study, in parallel, their properties in vitro. We show
      that, in vitro, BMSC-conditioned medium (BMSC-CM) protects neurons from
      apoptosis, activates macrophages and is pro-angiogenic. In vivo, BMSC-CM
      administered after spinal cord contusion improves motor recovery. Histological
      analysis confirms the pro-angiogenic action of BMSC-CM, as well as a tissue
      protection effect. Finally, the characterization of BMSC-CM by cytokine array and
      ELISA identified trophic factors as well as cytokines likely involved in the
      beneficial observed effects. In conclusion, our results support the paracrine
      mediated mode of action of BMSCs and raise the possibility to develop a cell-free
      therapeutic approach. 

PMID- 24013450
TI  - Theoretical study on cooperative effects between X?N and X?Carbene halogen bonds
      (X = F,Cl,Br and I).
AB  - Quantum chemical calculations are performed to study the interplay between
      halogen?nitrogen and halogen?carbene interactions in NCX?NCX?CH2 complexes, where
      X = F, Cl, Br and I. Molecular geometries and interaction energies of dyads and
      triads are investigated at the MP2/aug-cc-pVTZ level of theory. It is found that
      the X?N and X?Ccarbene interaction energies in the triads are larger than those
      in the dyads, indicating that both the halogen bonding interactions are enhanced.
      The estimated values of cooperative energy E coop are all negative with much
      larger E coop in absolute value for the systems including iodine. The nature of
      halogen bond interactions of the complexes is analyzed using parameters derived
      from the quantum theory atoms in molecules methodology and energy decomposition
      analysis.

PMID- 24013451
TI  - Letter from the editor.

PMID- 24013452
TI  - Genetic design of enhanced valley splitting towards a spin qubit in silicon.
AB  - The long spin coherence time and microelectronics compatibility of Si makes it an
      attractive material for realizing solid-state qubits. Unfortunately, the orbital
      (valley) degeneracy of the conduction band of bulk Si makes it difficult to
      isolate individual two-level spin-1/2 states, limiting their development. This
      degeneracy is lifted within Si quantum wells clad between Ge-Si alloy barrier
      layers, but the magnitude of the valley splittings achieved so far is small--of
      the order of 1 meV or less--degrading the fidelity of information stored within
      such a qubit. Here we combine an atomistic pseudopotential theory with a genetic
      search algorithm to optimize the structure of layered-Ge/Si-clad Si quantum wells
      to improve this splitting. We identify an optimal sequence of multiple Ge/Si
      barrier layers that more effectively isolates the electron ground state of a Si
      quantum well and increases the valley splitting by an order of magnitude, to ~9
      meV.

PMID- 24013453
TI  - IL-17C expression in nasal epithelial cells of chronic rhinosinusitis with nasal
      polyposis.
AB  - Interleukin 17C (IL-17C) is a functionally distinct member of the IL-17 family
      that is selectively induced in epithelia by bacterial challenge and inflammatory
      stimuli. The goal of this study was to explore the expression of IL-17C in nasal
      epithelial cells and their role in the pathogenesis of chronic rhinosinusitis
      with nasal polyposis (CRSwNPs). IL-17C expression was detected using
      immunohistochemistry (IHC) of the epithelial cell layers and using the western
      blot assay on whole tissue homogenates from control subjects (n = 10) and CRSwNP
      patients [10 non-eosinophilic polyps and 10 eosinophilic polyps (EPs)].
      Expression of IL-17C and P47-phox were evaluated in the human nasal epithelial
      cells (RPMI-2650 cells) after treatment with staphylococcal enterotoxin B (SEB)
      and pretreatment with reactive oxygen species (ROS) scavenger, N-acetyl L
      cysteine (NAC). Finally, IL-17C expression was demonstrated in eosinophilic
      rhinosinusitis murine model using IHC. Epithelial expression of IL-17C was higher
      in nasal polyps (especially in EPs) compared to control mucosa. SEB increased the
      expression of IL-17C and P47-phox in RPMI-2650 cells. SEB-induced expressions of
      both IL-17C and P47-phox were significantly decreased in NAC-pretreated cells.
      Epithelial expression of IL-17C was significantly higher in experimental mice
      compared to control mice. SEB-induced IL-17C expression in nasal epithelial cells
      is mediated by ROS production. This pathway may be associated with the
      pathogenesis of CRSwNP, especially eosinophilic nasal polyps. 

PMID- 24013454
TI  - Helium focused ion beam fabricated plasmonic antennas with sub-5 nm gaps.
AB  - We demonstrate a reliable fabrication method to produce plasmonic dipole
      nanoantennas with gap values in the range of 3.5-20 nm. The method combines
      electron beam lithography to create gold nanorods and helium focused ion beam
      milling to cut the gaps. Results show a reproducibility within 1 nm. Scattering
      spectra of antennas show a red shift of resonance wavelengths and an increase of
      the intensity of resonance peaks with a decrease of the gap size, which is in
      agreement with finite element simulations. The measured refractive index
      sensitivity was about 250 nm per refractive index unit for antennas with gap
      values below 5 nm. 

PMID- 24013455
TI  - Neural and behavioral evidence for an intrinsic cost of self-control.
AB  - The capacity for self-control is critical to adaptive functioning, yet our
      knowledge of the underlying processes and mechanisms is presently only inchoate.
      Theoretical work in economics has suggested a model of self-control centering on
      two key assumptions: (1) a division within the decision-maker between two
      'selves' with differing preferences; (2) the idea that self-control is
      intrinsically costly. Neuroscience has recently generated findings supporting the
      'dual-self' assumption. The idea of self-control costs, in contrast, has remained
      speculative. We report the first independent evidence for self-control costs.
      Through a neuroimaging meta-analysis, we establish an anatomical link between
      self-control and the registration of cognitive effort costs. This link predicts
      that individuals who strongly avoid cognitive demand should also display poor
      self-control. To test this, we conducted a behavioral experiment leveraging a
      measure of demand avoidance along with two measures of self-control. The results
      obtained provide clear support for the idea of self-control costs. 

PMID- 24013456
TI  - Examination of artificial MiRNA mimics with centered-site complementarity for
      gene targeting.
AB  - BACKGROUND: MiRNA primarily acts to repress gene expression at the post
      transcriptional level through imperfect complementarity of its 5' region to the
      "seed site" in the 3' untranslated region of target mRNAs, with its "3'
      supplementary site" and "center site" also playing important roles under certain
      circumstances. The aim of this study was to test if artificial miRNA mimics (miR
      Mimics) that are designed to target the "centered sites" without "seed sites"
      complementarity are able to repress gene expression as natural miRNAs. METHODS:
      We designed miR-Mimics carrying centered-site matches (CS-miR-Mimics) or seed
      site matches (SS-miR-Mimics) and siRNA to two antiapoptotic genes BCL2 and AKT1.
      We tested the gene targeting of these constructs using real-time RT-PCR and
      Western blot to quantify mRNA and protein levels of BCL2 and AKT1, respectively,
      luciferase reporter gene assay to investigate the interaction between miR-Mimics
      and their target sites, and cell survival assay to study the functional outcomes
      of the miR-Mimics. RESULTS: We found that CS-miR-Mimic, SS-miR-Mimic and siRNA,
      all down regulated the mRNA and protein levels of their cognate target BCL2 or
      AKT1 in a concentration-dependent manner. Luciferase reporter gene assay further
      confirmed the functional interactions of CS-miR-Mimic, SS-miR-Mimic and siRNA
      with their target sites. We then observed that the miR-Mimics and siRNAs were all
      able to induce cell death, as indicated by the reduced survival rate of cells.
      CONCLUSIONS: We have provided evidence for the feasibility of CS-miR-Mimics for
      post-transcriptional repression of genes, which can be designed to have reduced
      numbers of seed type off-target sites compared to the number of target sites from
      an average endogenous seed-site miRNA. CS-miR-Mimics may be a novel approach for
      miRNA research requiring miRNA gain-of-function.

PMID- 24013457
TI  - Bone Marrow Transplantation Alters the Tremor Phenotype in the Murine Model of
      Globoid-Cell Leukodystrophy.
AB  - Tremor is a prominent phenotype of the twitcher mouse, an authentic genetic model
      of Globoid-Cell Leukodystrophy (GLD, Krabbe's disease). In the current study, the
      tremor was quantified using a force-plate actometer designed to accommodate low
      weight mice. The actometer records the force oscillations caused by a mouse's
      movements, and the rhythmic structure of the force variations can be revealed.
      Results showed that twitcher mice had significantly increased power across a
      broad band of higher frequencies compared to wildtype mice. Bone marrow
      transplantation (BMT), the only available therapy for GLD, worsened the tremor in
      the twitcher mice and induced a measureable alteration of movement phenotype in
      the wildtype mice. These data highlight the damaging effects of conditioning
      radiation and BMT in the neonatal period. The behavioral methodology used herein
      provides a quantitative approach for assessing the efficacy of potential
      therapeutic interventions for Krabbe's disease. 

PMID- 24013458
TI  - A selected screening programme was less effective in the detection of methicillin
      resistant Staphylococcus aureus colonisation in an orthopaedic unit.
AB  - PURPOSE: Our unit has used a selective screening policy for methicillin-resistant
      Staphylococcus aureus (MRSA) colonisation using standard chromogenic growth
      media, based upon risk stratification. The aim of this study was to examine the
      effectiveness of this selective screening policy. METHODS: A cohort of 429
      patients was assessed for their risk status for MRSA colonisation using both
      rapid polymerase chain reaction (PCR) swabs and traditional culture and
      sensitivity analysis. The sensitivity, specificity, positive predictive values
      and negative predictive values of the traditional selective approach were
      calculated compared to universal rapid screening. RESULTS: One hundred eighteen
      patients were considered high risk and would traditionally be further screened
      with standard culture of swabs. The prevalence of MRSA was 15/429 (3.5%). The
      sensitivity of selective screening was 53% identifying eight of 15 cases. The
      false-negative rate was therefore 47% and seven would have been missed. PCR
      results were available within four to six hours, whereas culture results were
      only available at 24 hours for the media showing no growth and not until 72 hours
      for positive MRSA cases. CONCLUSIONS: We now advocate universal screening prior
      to, or on admission, using this rapid PCR test, as we consider this identifies
      MRSA colonisation more effectively and facilitates "ring-fencing" of orthopaedic
      beds.

PMID- 24013459
TI  - Repair of segmental long-bone defects by stem cell concentrate augmented
      scaffolds: a clinical and positron emission tomography--computed tomography
      analysis.
AB  - PURPOSE: Treating segmental long-bone defects remains a major challenge. For
      defects >3 cm, segmental transport represents the gold standard, even though the
      method is time consuming and afflicted with several complications. The aim of
      this study was to evaluate healing of such defects after grafting an osteogenic
      scaffold previously seeded with stem cell concentrate. METHODS: We evaluated five
      patients with segmental long-bone defects (3-14 cm) treated with bone marrow
      aspirate concentrates (BMAC) seeded onto a bovine xenogenous scaffold. The
      healing process was monitored by X-rays and positron emission tomography-computed
      tomography (PET-CT) three months after surgery. RESULTS: Centrifugation led to a
      concentration of leukocytes by factor 8.1 +/- 7.5. Full weight bearing was
      achieved 11.3 +/- 5.0 weeks after surgery. PET analysis showed an increased
      influx of fluoride by factor 8.3 +/- 6.4 compared with the contralateral side (p
      < 0.01). Bone density in the cortical area was 75 +/- 16 % of the contralateral
      side (p < 0.03). The patient with the largest defect sustained an implant failure
      in the distal femur and finally accomplished therapy by segmental transport. He
      also had the lowest uptake of fluoride of the patient collective (2.2-fold
      increase). CONCLUSION: Stem cell concentrates can be an alternative to segmental
      bone transport. Further studies are needed to compare this method with autologous
      bone grafting and segmental transport.

PMID- 24013460
TI  - Coracoid graft positioning in the Latarjet procedure.
AB  - PURPOSE: The success of shoulder stabilization with the Latarjet procedure
      depends on the correct positioning of the coracoid graft at the glenoid. The aim
      of this study was to assess intra-observer reproducibility and inter-observer
      reproducibility of a new standardized CT scan analysis for coracoid graft
      positioning in the axial plane after the Latarjet procedure and to assess the
      positioning in the study group. METHODS: A consecutive series of 27 patients (22
      men, 5 woman, 26.1 +/- 6.4 years-13 right, 14 left shoulders) were followed up
      with CT scans between 2010 and 2012. The analysis of the CT scans (2.4 +/- 0.7
      months postoperatively) was performed with OsirixTM software. The assessment
      included two criteria in the axial plane: relation of the graft to the articular
      surface of the glenoid and impingement of the graft with the maximal humeral head
      circumference. Grafts were judged to be lateral, congruent, flush or medial. The
      strength of intra-observer agreement and inter-observer agreement was measured by
      the Kappa coefficient. RESULTS: The Kappa coefficient for intra-observer
      agreement was "substantial" (K = 0.64 +/- 0.14, z = 4.6) to "almost perfect" (K =
      0.81 +/- 0.14, z = 5.7). The Kappa coefficient for inter-observer variability was
      "substantial" (K = 0.59 +/- 0.14, z = 4.3) to "almost perfect" (K = 0.89 +/-
      0.14, z = 6.0). In our study, in the axial plane, 3 (11 %) transplants were
      lateral; 6 (22 %) transplants were congruent; 16 (60 %) flush and 2 (7 %) medial.
      CONCLUSION: This standardized CT scan analysis after Latarjet procedure has shown
      to accurately describe graft positioning in the axial plane with both good intra
      observer reproducibility and inter-observer reproducibility. LEVEL OF EVIDENCE:
      Case series, treatment study, Level IV.

PMID- 24013461
TI  - A new spacer-guided, PCL balancing technique for cruciate-retaining total knee
      replacement.
AB  - PURPOSE: The goal of this study was to investigate whether a new posterior
      cruciate ligament (PCL) balancing approach with a spacer technique during total
      knee arthroplasty (TKA) reproduced the correct tibiofemoral contact point (CP)
      location. It was hypothesized that it should be possible to adequately balance
      the PCL with this geometrical technique, obtaining correct position and stability
      of the medial femoral condyle, independent of insert shape. METHODS: Nine fresh
      frozen full-leg cadaver specimens were used. After native testing, prototype
      components of a new PCL-retaining implant were implanted using navigation and a
      bone-referencing technique. After finishing the bone cuts, the spacer technique
      was used to ascertain balancing of the PCL and the tibial cut was corrected if
      necessary. Passive and squat motions were performed before and after TKA using a
      dynamic knee simulator while tibiofemoral kinematics were recorded using six
      infrared cameras. CPs (native and implant) were calculated as the projections of
      the femoral condylar centres on the horizontal plane of the tibia. RESULTS: The
      spacer technique resulted in correct PCL balancing in all specimens. The
      kinematic patterns of native and replaced knees showed no statistically
      significant differences in passive and squat motions. The medial CP after TKA was
      at the same position as in the native knee. No paradoxical sliding forward was
      seen after TKA, supporting our hypothesis. CONCLUSIONS: The spacer technique can
      be applied by surgeons during PCL-retaining TKA and will lead to good PCL
      balancing, indicated by a correct CP, no lift-off in flexion and no posterior
      sag.

PMID- 24013462
TI  - Cationic-anionic mediated charge compensation on La2Ti2O7 for visible light
      photocatalysis.
AB  - The cationic-anionic mediated charge compensation effect was studied in the
      layered perovskite La2Ti2O7 for the visible light photocatalysis. Our screened
      hybrid density functional study shows that the electronic structure of La2Ti2O7
      can be tuned by the cationic (V, Nb, Ta)/anionic (N) mono- and co-doping. Such
      mono-doping creates impurity states in the band gap which helps the electron-hole
      recombination. But if the charge compensation is made by the cationic-anionic
      mediated co-doping then such impurity states can be removed and can be a
      promising strategy for visible light photocatalysis. The absolute band edge
      position of the doped La2Ti2O7 has been aligned with respect to the water
      oxidation/reduction potential. The calculated defect formation energy shows the
      stability of the co-doping system is improved due to the coulomb interactions and
      charge compensations effect. 

PMID- 24013464
TI  - Aspirations of Latina adolescent suicide attempters.
AB  - Parents' aspirations and expectations are communicated to their offspring.
      Children internalize their parents' aspirations and accept some of the
      expectations while rejecting others, all part of the developmental process and
      identity-consolidation. When the aspirations and expectations of youth and
      parents are incongruent, the outcomes in youths' behavior can be deleterious,
      such as when adolescents manifest suicidal behaviors. We examined aspirations
      expressed by 12 Latina adolescent suicide attempters and their parents and
      compared them to 12 non-suicidal Latinas and parents. Qualitative analyses
      revealed that incongruence of aspirations between girls and their parents were
      greater among suicidal teens. Suicidal and non-suicidal Latinas presented
      contrasting aspirations: the former on gaining independence and the latter on
      completing their education and pursuing careers. Findings may inform
      developmental research and ways in which clinicians and policymakers can help
      Latinas achieve their own and their parents' aspirations.

PMID- 24013463
TI  - Increased plasma concentrations of vitamin D metabolites and vitamin D binding
      protein in women using hormonal contraceptives: a cross-sectional study.
AB  - Use of hormonal contraceptives (HC) may influence total plasma concentrations of
      vitamin D metabolites. A likely cause is an increased synthesis of vitamin D
      binding protein (VDBP). Discrepant results are reported on whether the use of HC
      affects free concentrations of vitamin D metabolites. AIM: In a cross-sectional
      study, plasma concentrations of vitamin D metabolites, VDBP, and the calculated
      free vitamin D index in users and non-users of HC were compared and markers of
      calcium and bone metabolism investigated. RESULTS: 75 Caucasian women aged 25-35
      years were included during winter season. Compared with non-users (n = 23), users
      of HC (n = 52) had significantly higher plasma concentrations of 25
      hydroxyvitamin D (25OHD) (median 84 interquartile range: [67-111] vs. 70 [47-83]
      nmol/L, p = 0.01), 1,25-dihydroxyvitamin D (1,25(OH)2D) (198 [163-241] vs. 158
      [123-183] pmol/L, p = 0.01) and VDBP (358 [260-432] vs. 271 [179-302] ug/mL, p <
      0.001). However, the calculated free indices (FI-25OHD and FI-1,25(OH)2D) were
      not significantly different between groups (p > 0.10). There were no significant
      differences in indices of calcium homeostasis (plasma concentrations of calcium,
      parathyroid hormone, and calcitonin, p > 0.21) or bone metabolism (plasma bone
      specific alkaline phosphatase, osteocalcin, and urinary NTX/creatinine ratio)
      between groups. IN CONCLUSION: Use of HC is associated with 13%-25% higher
      concentrations of total vitamin D metabolites and VDBP. This however is not
      reflected in indices of calcium or bone metabolism. Use of HC should be
      considered in the interpretation of plasma concentrations vitamin D metabolites.

PMID- 24013465
TI  - The impact of the Affordable Care Act on health education: perceptions of leading
      health educators.
AB  - The health care system in the United States is being overhauled by major
      legislation, the Patient Protection and Affordable Care Act (ACA). This study's
      goal was to provide insight into the perceived impact and changes that could
      occur within the health education profession as a result of this health care
      reform legislation. Seven leaders of the health education profession participated
      in this qualitative research study. Six semistructured, exploratory interviews
      were conducted, and one participant provided written responses to the interview
      questions. A thematic analysis of the content of the interviews yielded five
      themes: (a) a fragmented sick-care system, (b) ACA becomes law: the participants'
      reactions, (c) ACA becomes law: the profession's reactions, (d) impact on the
      profession, and (e) health education in 2020. This article describes the fourth
      theme, the impact of the ACA on the health education profession. Leaders of the
      health education profession believed that the ACA creates a more favorable
      environment for health education practice. The positive elements of this
      legislation, however, will need to be protected, strengthened, and verified,
      through the work of health education professionals. As more mandates within the
      law are enacted over time, the impact on the profession, more than likely, will
      shift. 

PMID- 24013466
TI  - FosPeg(r) PDT alters the EBV miRNAs and LMP1 protein expression in EBV positive
      nasopharyngeal carcinoma cells.
AB  - Nasopharyngeal carcinoma (NPC) is one of the top ten cancers highly prevalent in
      Hong Kong and South China. Epstein-Barr virus (EBV) infection contributes to the
      tumorigenesis of NPC through the expression of different viral proteins. Among
      these, Latent Membrane Protein 1(LMP1) is the major oncoprotein expressed by EBV.
      Foscan(r) (Biolitec AG), m-tetrahydroxyphenylchlorin (mTHPC)-based
      photosensitizing drug, has been used in the photodynamic therapy (PDT) for head
      and neck cancers. FosPeg(r) (Biolitec AG) is a new formulation of mTHPC contained
      in PEGylated liposomes with optimized distribution properties. In this in vitro
      study, the potential of FosPeg(r)-PDT on human EBV positive NPC cell (c666-1) and
      EBV negative cells (HK1 and CNE2) were investigated. Effects of FosPeg(r)-PDT on
      the expression of EBV BART miRNAs (EBV miRNA BART 1-5p, BART 16, and BART 17-5p),
      LMP1 mRNA and proteins on c666-1 cells were also elucidated. The killing efficacy
      of FosPeg(r)-PDT on NPC cells were determined by MTT assay after LED activation.
      Effects of FosPeg(r)-PDT on the expression of LMP1 mRNA and protein were examined
      by real time PCR and western blot analysis. FosPeg(r)-PDT demonstrated its
      antitumor effect on c666-1 cells in a drug and light dose dependent manner. LD30,
      LD50 and LD70 were achieved by applying LED activation (3J/cm(2)) at 4h post
      incubated cells with 0.05MUg/ml, 0.07MUg/ml and 0.3MUg/ml FosPeg(r),
      respectively. Up-regulation of both LMP1 mRNA and protein were observed after
      FosPeg(r)-PDT in a dose dependent manner. FosPeg(r)-PDT exerted antitumor effect
      on c666-1 cells through up-regulation of LMP1 protein. Understanding the
      mechanism of FosPeg(r)-PDT may help to develop better strategies for the
      treatment of NPC. 

PMID- 24013467
TI  - Endoscopic stenting for benign upper gastrointestinal strictures and leaks.
AB  - BACKGROUND: Self-expandable metal stents (SEMS) and self-expandable plastic
      stents (SEPS) maybe used for the treatment of benign upper gastrointestinal (GI)
      leaks and strictures. This study reviewed our experience with stent insertions in
      patients with benign upper GI conditions. METHODS: Patients who underwent stent
      placement for benign upper GI strictures and leaks between March 2007 and April
      2011 at a tertiary referral academic center were studied using an endoscopic
      database and electronic patient records. The technical success, complications,
      and clinical improvement after stent removal were compared according to type of
      stent. The outcomes measured were clinical response, adverse events, and
      predictors of stent migration. RESULTS: Thirty-eight patients (50 % male, mean
      age = 54 years, range = 12-82) underwent 121 endoscopic procedures. Twenty
      patients had stents placed for strictures, and 18 had stents placed for leaks.
      Stent placement was technically successful in all patients. The average duration
      of stent placement was 54 days (range = 18-118). Clinical improvement immediately
      after stent placement was seen in 29 of the 38 patients (76.3 %). Immediate post
      procedure adverse events occurred in 8 patients. Late adverse events were seen in
      18 patients. Evidence of stent migration occurred in 16 patients and was seen in
      42 of the 118 successfully placed stents (35.5 %). Migration was more frequent
      with fully covered SEMS (p = 0.002). After stent removal, 27 patients were
      evaluable for long-term success (median follow-up time of 283 days, IQR 38-762).
      Resolution of strictures or leaks was seen in 11 patients (40.7 %). Predictors
      for long-term success included increasing age and if the stent did not cross the
      GE junction. CONCLUSIONS: Placement of SEPS and SEMS for benign refractory
      strictures and fistulas has modest long-term clinical efficacy and is limited by
      a significant migration rate. Stent migration is common and frequent with fully
      covered SEMS compared to other types of stents, regardless of indication or
      location.

PMID- 24013468
TI  - Incidence, mechanisms, and outcomes of esophageal and gastric perforation during
      laparoscopic foregut surgery: a retrospective review of 1,223 foregut cases.
AB  - BACKGROUND: Intraoperative perforation is a potentially major complication of
      laparoscopic (lap) foregut surgery. This study analyzed the incidence, mechanism,
      and outcomes of intraoperative perforations during these procedures in a large
      institutional experience. METHODS: All patients who underwent lap foregut surgery
      including laparoscopic antireflux surgery (LARS), paraesophageal hernia (PEH)
      repair, Heller myotomy, and reoperative hiatal hernia (redo HH) repair at the
      authors' institution from August 2004 to September 2012 were reviewed
      retrospectively. Perforation events and postoperative outcomes were analyzed, and
      complications were graded by the modified Clavien system. All data are expressed
      as means +/- standard deviations or as medians. Statistical analysis was
      performed using Fisher's exact test and the Mann-Whitney U test. RESULTS: In this
      study, the repairs for 1,223 patients were analyzed (381 LARS procedures, 379 PEH
      repairs, 313 Heller myotomies, 150 redo HH repairs). Overall, 51 patients (4.2 %)
      had 56 perforations resulting from LARS (n = 4, 1 %), PEH repair (n = 7, 1.8 %),
      Heller myotomy (n = 18, 5.8 %), and redo HH repair (n = 22, 14.6 %). Redo HH was
      significantly more likely to result in perforations than LARS or PEH repair (p <
      0.001). The locations of the perforations were esophageal in 13 patients (23.6
      %), gastric in 40 patients (72.7 %), and indeterminate in 2 patients (3.6 %). The
      most common mechanisms of perforations were suture placement for LARS (75 %) and
      traction for PEH repair (43 %) and for Heller myotomy during the myotomy (72 %).
      The most redo HH perforations resulted from dissection/wrap takedown (73 %) and
      traction (14 %). Perforations were recognized and repaired intraoperatively in 43
      cases (84 %) and postoperatively in eight cases (16 %). Perforations discovered
      postoperatively were more likely to require reoperation (75 vs 2 %; p < 0.001),
      to require more gastrointestinal and radiologic interventions (50 vs 2 %; p =
      0.004), and to have higher morbidity (88 vs 26 %; p = 0.004) than perforations
      recognized intraoperatively. CONCLUSIONS: In a high-volume center, intraoperative
      perforations are the most frequent with reoperative HH repair. If perforations
      are recognized and repaired intraoperatively, they require minimal postoperative
      intervention. Unrecognized perforations usually require reoperation and result in
      significantly greater morbidity.

PMID- 24013469
TI  - Laparoscopic total gastrectomy for remnant gastric cancer: feasibility study.
AB  - BACKGROUND: The benefits and feasibility of laparoscopic surgery for remnant
      gastric cancer are still unclear. The purpose of this study was to describe the
      detailed procedure and to evaluate the clinical short-term outcomes of
      laparoscopic total gastrectomy (LTG) compared with open total gastrectomy (OTG)
      for remnant gastric cancer (RGC). METHODS: Of 1,247 consecutive patients who
      underwent gastrectomy for gastric cancer in our department at Kyushu University
      Hospital from January 1996 to May 2012, 22 patients who underwent successful
      curative resection of RGC with precise nodal dissection were enrolled in this
      study. Twelve patients underwent LTG and the remaining ten patients underwent
      OTG. We analyzed the clinical short-term outcomes of LTG and compared the results
      between LTG and OTG groups to evaluate the safety and feasibility of LTG.
      RESULTS: Twelve patients with RGC successfully underwent LTG without open
      conversion and morbidity. The mean operation time of LTG, 362.3 +/- 68.4 min, was
      significantly longer than that of OTG (p = 0.0176), but the mean blood loss of
      LTG, 65.8 +/- 62 g, was smaller than that of OTG (p < 0.01). The mean
      postoperative times to resumption of water and food intake were significantly
      shorter in the LTG group than in the OTG group (p < 0.01). The overall 3-year
      survival rate was comparable between the LTG and OTG groups (77.8 vs. 100 %; p =
      0.9406). CONCLUSIONS: This study shows that LTG is a feasible and reliable
      procedure for the treatment of RGC in terms of short-term outcomes.

PMID- 24013470
TI  - Laparoscopic-assisted versus open total mesorectal excision with anal sphincter
      preservation for mid and low rectal cancer: a prospective, randomized trial.
AB  - BACKGROUND: This single-center, prospective, randomized trial was designed to
      compare the short-term clinical outcome between laparoscopic-assisted versus open
      total mesorectal excision (TME) with anal sphincter preservation (ASP) in
      patients with mid and low rectal cancer. Long-term morbidity and survival data
      also were recorded and compared between the two groups. METHODS: Between August
      2001 and August 2007, 80 patients with mid and low rectal cancer were randomized
      to receive either laparoscopic-assisted (40 patients) or open (40 patients) TME
      with ASP. The median follow-up time for all patients was 75.7 (range 16.9-115.7)
      months for the laparoscopic-assisted group and 76.1 (range 4.7-126.6) months for
      the open group. The primary endpoint of the study was short-term clinical
      outcome. Secondary endpoints included long-term morbidity rate and survival. Data
      were analyzed by intention-to-treat principle. RESULTS: The demographic data of
      the two groups were comparable. Postoperative recovery was better after
      laparoscopic surgery, with less analgesic requirement (P < 0.001), earlier
      mobilization (P = 0.001), lower short-term morbidity rate (P = 0.043), and a
      trend towards shorter hospital stay (P = 0.071). The cumulative long-term
      morbidity rate also was lower in the laparoscopic-assisted group (P = 0.019). The
      oncologic clearance in terms of macroscopic quality of the TME specimen,
      circumferential resection margin involvement, and number of lymph nodes removed
      was similar between both groups. After curative resection, the probabilities of
      survival at 5 years of the laparoscopic-assisted and open groups were 85.9 and
      91.3 %, respectively (P = 0.912). The respective probabilities of being disease
      free were 83.3 and 74.5 % (P = 0.114). CONCLUSIONS: Laparoscopic-assisted TME
      with ASP improves postoperative recovery, reduces short-term and long-term
      morbidity rates, and seemingly does not jeopardize survival compared with open
      surgery for mid and low rectal cancer ( http://ClinicalTrials.gov Identifier:
      NCT00485316).

PMID- 24013471
TI  - Body composition, anthropometrics, energy expenditure, systemic inflammation, in
      premenopausal women 1 year after laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is currently the most
      common bariatric procedure and results in a substantial weight loss and recovery
      from obesity-related comorbidities, both of which are maintained in the long
      term. However, besides the desired loss of fat mass, LRYGBP is also followed by
      the loss of fat-free mass (FFM). We aimed to determine the factors associated
      with the loss of >=20 % of the initial FFM 1 year after LRYGBP in a prospective
      series of 115 Caucasian, premenopausal women. METHODS: Anthropometrics, body
      composition (bioelectrical impedance analysis), resting energy expenditure (REE)
      (indirect calorimetry), inflammation, insulin resistance, and lipid disturbances
      were determined before and 1 year after LRYGBP. RESULTS: The mean loss of initial
      FFM was 15.3 +/- 13.8 %. 1 year after LRYGBP, 81 women lost <20 % (<20 % FFM
      group) and 35 lost >=20 % (>=20 % FFM group) of the initial FFM. Before surgery,
      the FFM, weight, BMI, excess BMI, brachial circumference, waist circumference,
      and REE were significantly higher in the >=20 % FFM group while inflammation,
      insulin resistance, and lipid disturbances were comparable between the two
      groups. 1 year after LRYGBP, the FFM, weight, BMI, excess BMI, brachial
      circumference, waist circumference, and REE decreased significantly and were
      comparable between the two groups. Inflammation, insulin resistance, and lipid
      disturbances improved comparably between the two groups after surgery. The only
      variable associated with the loss of >=20 % of the initial FFM in the
      multivariable analysis was the presence of more FFM before surgery (67.0 +/- 9.9
      vs. 53.5 +/- 6.7 kg). CONCLUSIONS: One year after LRYGBP the loss of >=20 % of
      the initial FFM occurred mainly in women with more FFM before surgery and
      resulted in the same body composition of women who lost <20 % of the initial FFM.

PMID- 24013472
TI  - Submucosal tunneling endoscopic resection for small upper gastrointestinal
      subepithelial tumors originating from the muscularis propria layer.
AB  - BACKGROUND: This prospective study was designed to evaluate the safety and
      efficacy of submucosal tunneling endoscopic resection (STER) for small (<=3 cm)
      upper gastrointestinal (GI) subepithelial tumors (SETs) originating from the
      muscularis propria (MP) layer. METHODS: Between August 2011 and February 2013, a
      total of 85 patients with upper GI SETs originating from the MP layer were
      treated with STER. The key steps were as follows: (1) locating the tumor by
      injection of methylene blue or indigo carmine and then creating a submucosal
      tunnel from 5 cm above the tumor between the submucosal and muscular layers; (2)
      resecting the tumor by endoscopic resection techniques; (3) closing the mucosal
      incision site with several clips after the tumor is removed. RESULTS: Of the 85
      SETs, 60 were located in the esophagus, 16 in the cardia, and 9 in the stomach.
      STER was successfully performed in all cases (success rate: 100 %). The mean
      tumor size was 19.2 mm. The mean procedure time was 57.2 min. The average
      hospital stay after the procedure was 5.9 days. Pathological diagnosis of the
      tumors were leiomyoma (65/85), gastrointestinal stromal tumor (GIST) (19/85), and
      calcifying fibrous tumor (1/85). During the procedure, eight patients developed
      pneumothorax, subcutaneous emphysema, and/or pneumoperitoneum. These patients
      recovered after conservative treatment. The rate of all complications was
      significantly higher for lesions originating in the deeper MP layer (70 %) than
      in the superficial MP layer (1.3 %; p < 0.001). The total complication rate for
      different histological diagnoses was also significantly different (26.3 % for
      GISTs, 4.6 % for leiomyomas, 0 % for calcifying fibrous tumors, p < 0.05). No
      residual or recurrent tumors were detected during the follow-up period (median: 8
      months). CONCLUSIONS: Submucosal tunneling endoscopic resection appears to be a
      feasible, safe, and effective procedure for treatment of small (<=3 cm) upper GI
      SETs originating from the MP layer.

PMID- 24013473
TI  - Laparoscopic surgery in the treatment of liver hydatid cysts.

PMID- 24013474
TI  - Effect of a pi-spacer between a donor and an acceptor on small molecule-based
      data-storage device performance.
AB  - We demonstrate that replacing the hydrazone linkage by a linear pi-spacer
      bridging a carbazole donor and a naphthalimide acceptor induces a critical change
      in molecular organization and electron density distribution in the conjugation
      backbone that correlates with a remarkable variation of memory performance from
      DRAM to WORM types. 

PMID- 24013475
TI  - Potential of wound dressing composed of hyaluronic acid containing epidermal
      growth factor to enhance cytokine production by fibroblasts.
AB  - This study aimed to investigate the potential of a wound dressing composed of
      hyaluronic acid (HA) containing epidermal growth factor (EGF) to enhance cytokine
      production by fibroblasts. The present wound dressing has a two-layered spongy
      structure: an upper layer composed of crosslinked high-molecular-weight HA, and a
      lower layer composed of low-molecular-weight HA containing arginine (Arg) and
      vitamin C derivative (VC) with or without EGF. Human fibroblast-embedded collagen
      gel sheet (cultured dermal substitute: CDS) was elevated to the interface between
      the air and culture medium to create a wound surface model onto which each wound
      dressing was placed, which was followed by culture for 7 days. The EGF dressing
      (with EGF, Arg, VC) significantly enhanced the production of vascular endothelial
      growth factor (VEGF) and hepatocyte growth factor (HGF) by CDS as compared to the
      EGF-free dressing (with Arg, VC). To evaluate if this enhanced production of VEGF
      and HGF achieved with the EGF dressing is sustained, a second experiment was
      conducted using a wound surface model. Each wound dressing was placed on the CDS
      in the wound surface model. Culture was then performed for 3 days (first period),
      after which each dressing was placed on another CDS for a further 3-day culture
      period (second period). The EGF dressing enhanced the production of VEGF and HGF
      by CDS during the first and second periods as compared to the corresponding
      production when using the EGF-free dressing. These results suggest that EGF can
      be maintained in the hydrated layer of a wound dressing composed of crosslinked
      high-molecular-weight HA. 

PMID- 24013476
TI  - Inducing effect on the percolation transition in complex networks.
AB  - Percolation theory concerns the emergence of connected clusters that percolate
      through a networked system. Previous studies ignored the effect that a node
      outside the percolating cluster may actively induce its inside neighbours to exit
      the percolating cluster. Here we study this inducing effect on the classical site
      percolation and K-core percolation, showing that the inducing effect always
      causes a discontinuous percolation transition. We precisely predict the
      percolation threshold and core size for uncorrelated random networks with
      arbitrary degree distributions. For low-dimensional lattices the percolation
      threshold fluctuates considerably over realizations, yet we can still predict the
      core size once the percolation occurs. The core sizes of real-world networks can
      also be well predicted using degree distribution as the only input. Our work
      therefore provides a theoretical framework for quantitatively understanding
      discontinuous breakdown phenomena in various complex systems. 

PMID- 24013477
TI  - Preventing in-hospital newborn falls: a literature review.
AB  - In-hospital newborn falls are arguably one of the most underresearched and
      underreported issues for organizations that care for newborn patients. From the
      few published statistics of in-hospital fall rates, we know that perhaps 600 to
      1,600 newborn falls occur annually. Many of these falls can result in injury or
      even death of the newborn, legal issues for the institution, and severe emotional
      stress to the caregiver(s) and parents. Therefore, we searched the literature to
      ascertain causation and associated risks associated with in-hospital newborn
      falls. This is an important issue for nurses to understand because not only can
      the newborn be harmed due to a fall, but the actual newborn fall can also elicit
      strong feelings of guilt and culpability in the caregiver(s). This article
      reviews the literature to examine what is known about the factors associated with
      in-hospital newborn falls, to explore prevention measures, and to present best
      practices for how to adopt safe-sleep policy to prevent newborn falls. 

PMID- 24013478
TI  - Emotion processing in Psychopathy Checklist-assessed psychopathy: a review of the
      literature.
AB  - Deficient emotional experience is recognized as one of the central features of
      psychopathy and an impressive body of empirical findings regarding emotion
      processing in psychopathy has amassed over the past several decades, resulting in
      two broad theoretical perspectives. The general emotional deficit perspective
      postulates a globally reduced capacity for emotional experience and processing
      across the emotional spectrum. In contrast, according to the specific emotional
      deficit perspective, psychopathy is associated with abnormal experience of only
      specific types of emotion; several distinct hypotheses have been proposed under
      this latter perspective. We systematically and critically review findings from
      peer-reviewed research of emotion processing in psychopathy in relation to the
      two theoretical perspectives. In general, findings suggest that, compared to
      controls, psychopaths exhibit behavioral, psychophysiologic, and regional brain
      activation anomalies when processing emotion, but their ratings of self-arousal
      and stimulus valence/intensity do not differ from controls. However, when
      behavioral findings are examined separately by emotion type, the overall pattern
      of findings is not clearly consistent with any of the dominant theoretical
      perspectives of emotion processing in psychopathy. We summarize the current state
      of the field, including consistencies and inconsistencies in the literature,
      offer alternative explanations for the findings, and outline directions for
      future research. 

PMID- 24013479
TI  - Photoreceptors for a light biotransducer: a comparative study of the electrical
      responses of two (type-1) opsins.
AB  - The increasing interest in photoactivated proteins as natural replacements for
      standard inorganic materials in photocells leads to the comparison analysis of
      bacteriorhodopsin and proteorhodopsin, two widely diffused proteins belonging to
      the family of type-1 opsins. These proteins share similar behaviors but exhibit
      relevant differences in the sequential chain of the amino acids constituting
      their tertiary structure. The use of an impedance network analog to model the
      protein main features provides a microscopic interpretation of a set of
      experiments on their photo-conductance properties. In particular, this model
      links the protein electrical responses to the tertiary structure and to the
      interactions between neighboring amino acids. The same model is also used to
      predict the small-signal response in terms of the Nyquist plot. Interestingly,
      these rhodopsins are found to behave like a wide-gap semiconductor with intrinsic
      conductivities of the order of 10-7 S cm-1.

PMID- 24013480
TI  - Is the clinical course of laryngeal typical carcinoid tumor indolent?

PMID- 24013481
TI  - Hot Spot-Localized Artificial Antibodies for Label-Free Plasmonic Biosensing.
AB  - The development of biomolecular imprinting over the last decade has raised
      promising perspectives in replacing natural antibodies with artificial
      antibodies. A significant number of reports have been dedicated to imprinting of
      organic and inorganic nanostructures, but very few were performed on
      nanomaterials with a transduction function. Herein we describe a relatively fast
      and efficient plasmonic hot spot-localized surface imprinting of gold nanorods
      using reversible template immobilization and siloxane co-polymerization. The
      technique enables a fine control of the imprinting process at the nanometer scale
      and provides a nanobiosensor with high selectivity and reusability. Proof of
      concept is established by the detection of neutrophil gelatinase-associated
      lipocalin (NGAL), a biomarker for acute kidney injury, using localized surface
      plasmon resonance spectroscopy. The work represents a valuable step towards
      plasmonic nanobiosensors with synthetic antibodies for label-free and cost
      efficient diagnostic assays. We expect that this novel class of surface imprinted
      plasmonic nanomaterials will open up new possibilities in advancing biomedical
      applications of plasmonic nanostructures.

PMID- 24013482
TI  - Near-UV radiation acts as a beneficial factor for physiological responses in
      cucumber plants.
AB  - Effects of near-UV radiation on the growth and physiological activity of cucumber
      plants were investigated morphologically, physiologically and biochemically using
      3-week-old seedlings grown under polyvinyl chloride films featuring transmission
      either above 290 nm or above 400 nm in growth chambers. The hypocotyl length and
      leaf area of cucumber seedlings were reduced but the thickness of leaves was
      enhanced by near-UV radiation, due to increased upper/lower epidermis thickness,
      palisade parenchyma thickness and volume of palisade parenchyma cells.
      Photosynthetic and respiratory activities were also promoted by near-UV
      radiation, associated with general enhancement of physiological/biochemical
      responses. Particularly, metabolic activities in the photosynthetic system of
      chloroplasts and the respiratory system of mitochondria were analyzed under the
      conditions of visible light with and without near-UV radiation. For example, the
      activities of NAD(P)-dependent enzymes such as glyceraldehyde-3-phosphate
      dehydrogenase (G3PDH) in chloroplasts and isocitrate dehydrogenase (ICDH) in
      mitochondria were elevated, along with levels of pyridine nucleotides
      (nicotinamide coenzymes) [NAD(H) and NADP(H)] and activity of NAD kinase (NADP
      forming enzyme). Taken together, these data suggest that promotion of cucumber
      plant growth by near-UV radiation involves activation of carbon and nitrogen
      metabolism in plants. The findings of this research showed that near-UV radiation
      reaching the Earth's surface is a beneficial factor for plant growth.

PMID- 24013483
TI  - Inflammatory mediators of systemic inflammation in neonatal sepsis.
AB  - OBJECTIVE AND DESIGN: Sepsis refers to severe systemic inflammation in response
      to invading pathogens. To understand the molecular events that initiate the
      systemic inflammatory response, various inflammatory mediators were analyzed in
      neonatal sepsis samples and compared with normal samples. MATERIALS AND METHODS:
      We initially measured the levels of the various classical inflammatory mediators
      such as acute phase proteins [C-reactive protein (CRP) and procalcitonin (PCT)],
      granule-associated mediators (NE, MPO and NO), proinflammatory cytokines [tumour
      necrosis factor-alpha (TNFalpha), IL-1beta and IL-6), antiinflammatory cytokines
      (IL-10 and IL-13) and chemokines [IL-8 and monocyte chemotactic protein (MCP-1)]
      and novel cytokines (IL-12/IL-23p40, IL-21 and IL-23) using ELISA. We also used
      the human inflammation antibody array membrane to profile the inflammatory
      proteins that are involved in neonatal sepsis. RESULTS: There were significantly
      higher levels of CRP (5.4 +/- 0.70 mg/L), PCT (1.500 +/- 0.2400 MUg/L); NE (499.2
      +/- 22.01 MUg/L), NO (54.22 +/- 3.131 MUM/L); TNFalpha (396.6 +/- 37.40 pg/mL),
      IL-1beta (445.3 +/- 34.25 pg/mL), IL-6 (320.9 +/- 43.38 pg/mL); IL-8 (429.5 +/-
      64.08 pg/mL) MCP-1 (626.25 +/- 88.91 pg/mL), IL-10 (81.80 +/- 9.45 pg/mL), IL
      12/IL-23p40 (30.25 +/- 0.6 pg/mL), IL-21 (8,263.3 +/- 526.8 pg/mL) and IL-23
      (6,083 +/- 781.3 pg/mL) in neonates with sepsis compared to normal. The levels of
      MPO (21.20 +/- 3.099 ng/mL) were downregulated, whereas there was no change in IL
      13 (188.7 +/- 10.63 pg/mL) levels in septic neonates when compared with normal.
      Using the human inflammation antibody array membrane, we detected the presence of
      17 inflammatory proteins such as IL-3, IL6R, IL12p40, IL-16, TNFalpha, TNFbeta,
      TNF R1, chemokines I-309, IP-10 (IFN-gamma inducible protein 10), MCP-1, MCP-2,
      MIP 1beta (macrophage inflammatory protein), MIP-1delta, eotaxin-2, growth
      factors TGFbeta1 (transforming growth factor beta), PDGF (platelet derived growth
      factor), and cell adhesion molecule ICAM-1 (intracellular adhesion molecule) that
      were upregulated whereas RANTES which was downregulated in neonatal sepsis.
      CONCLUSION: The simultaneous secretion and release of multiple mediators such as
      proinflammatory cytokines and chemokines, cell adhesion molecules, and growth
      factors were found to be involved in the initiation of systemic inflammation in
      neonatal sepsis. Therefore, measuring the concentration of multiple mediators may
      help in the early detection of neonatal sepsis and help to avoid unnecessary
      antibiotic treatment.

PMID- 24013484
TI  - Does the impact of urinary incontinence on quality of life differ based on age?
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study was to evaluate if the
      impact of urinary incontinence (UI) on quality of life (QOL) differs between
      women based on age. METHODS: A retrospective review of patients presenting for
      the management of UI was performed. Patients with UI and their corresponding
      degree of bother were identified by their responses to validated questionnaires.
      Distributions of comorbidities and types of UI were presented as frequencies and
      compared between age cohorts with a chi-square test. Mean scale scores were
      assessed for normality and a one-way analysis of variance with a post hoc
      Scheffe's test was used to compare the scores. RESULTS: Of 765 patients meeting
      inclusion criteria, 22.4 % were <45, 28.9 % were 45-55, and 48.8 % were >55 years
      of age. Women older than 55 were significantly more likely to have urge UI and
      mixed UI than their counterparts (p < 0.001). Women <45 and 45-55 were more
      negatively impacted in their ability to perform physical activities compared to
      women >55 (p = 0.004), whereas women >55 were significantly less likely to feel
      frustrated by their incontinence than women <45 (p = 0.022). However, there was
      no significant difference in overall impact of incontinence among groups (p =
      0.585). CONCLUSIONS: UI equally impacts the functional and psychological QOL in
      women regardless of age. UI in women <55 results in a greater negative impact on
      level of physical activity, whereas women <45 are significantly more frustrated.

PMID- 24013485
TI  - Commentary on "acute abdomen after abdominoplasty: differential diagnosis".

PMID- 24013486
TI  - Pacific deep circulation and ventilation controlled by tidal mixing away from the
      sea bottom.
AB  - Vertical mixing in the ocean is a key driver of the global ocean thermohaline
      circulation, one of the most important factors controlling past and future
      climate change. Prior observational and theoretical studies have focused on
      intense tidal mixing near the sea bottom (near-field mixing). However, ocean
      general circulation models that employ a parameterization of near-field mixing
      significantly underestimate the strength of the Pacific thermohaline circulation.
      Here we demonstrate that tidally induced mixing away from the sea bottom (far
      field mixing) is essential in controlling the Pacific thermohaline circulation.
      Via the addition of far-field mixing to a widely used tidal parameterization, we
      successfully simulate the Pacific thermohaline circulation. We also propose that
      far-field mixing is indispensable for explaining the presence of the world
      ocean's oldest water in the eastern North Pacific Ocean. Our findings suggest
      that far-field mixing controls ventilation of the deep Pacific Ocean, a process
      important for ocean carbon and biogeochemical cycles. 

PMID- 24013488
TI  - Surface roughness measurement on a wing aircraft by speckle correlation.
AB  - The study of the damage of aeronautical materials is important because it may
      change the microscopic surface structure profiles. The modification of
      geometrical surface properties can cause small instabilities and then a
      displacement of the boundary layer. One of the irregularities we can often find
      is surface roughness. Due to an increase of roughness and other effects, there
      may be extra momentum losses in the boundary layer and a modification in the
      parasite drag. In this paper we present a speckle method for measuring the
      surface roughness on an actual unmanned aircraft wing. The results show an
      inhomogeneous roughness distribution on the wing, as expected according to the
      anisotropic influence of the winds over the entire wing geometry. A calculation
      of the uncertainty of the technique is given. 

PMID- 24013487
TI  - The COMBREX project: design, methodology, and initial results.

PMID- 24013489
TI  - Underwater sensor nodes and networks.
AB  - Sensor technology has matured enough to be used in any type of environment. The
      appearance of new physical sensors has increased the range of environmental
      parameters for gathering data. Because of the huge amount of unexploited
      resources in the ocean environment, there is a need of new research in the field
      of sensors and sensor networks. This special issue is focused on collecting
      recent advances on underwater sensors and underwater sensor networks in order to
      measure, monitor, surveillance of and control of underwater environments. On the
      one hand, from the sensor node perspective, we will see works related with the
      deployment of physical sensors, development of sensor nodes and transceivers for
      sensor nodes, sensor measurement analysis and several issues such as layer 1 and
      2 protocols for underwater communication and sensor localization and positioning
      systems. On the other hand, from the sensor network perspective, we will see
      several architectures and protocols for underwater environments and analysis
      concerning sensor network measurements. Both sides will provide us a complete
      view of last scientific advances in this research field. 

PMID- 24013490
TI  - Automatic determination of validity of input data used in ellipsoid fitting MARG
      calibration algorithms.
AB  - Ellipsoid fitting algorithms are widely used to calibrate Magnetic Angular Rate
      and Gravity (MARG) sensors. These algorithms are based on the minimization of an
      error function that optimizes the parameters of a mathematical sensor model that
      is subsequently applied to calibrate the raw data. The convergence of this kind
      of algorithms to a correct solution is very sensitive to input data. Input
      calibration datasets must be properly distributed in space so data can be
      accurately fitted to the theoretical ellipsoid model. Gathering a well
      distributed set is not an easy task as it is difficult for the operator carrying
      out the maneuvers to keep a visual record of all the positions that have already
      been covered, as well as the remaining ones. It would be then desirable to have a
      system that gives feedback to the operator when the dataset is ready, or to
      enable the calibration process in auto-calibrated systems. In this work, we
      propose two different algorithms that analyze the goodness of the distributions
      by computing four different indicators. The first approach is based on a
      thresholding algorithm that uses only one indicator as its input and the second
      one is based on a Fuzzy Logic System (FLS) that estimates the calibration error
      for a given calibration set using a weighted combination of two indicators. Very
      accurate classification between valid and invalid datasets is achieved with
      average Area Under Curve (AUC) of up to 0:98. 

PMID- 24013491
TI  - Low-cost ultrasonic distance sensor arrays with networked error correction.
AB  - Distance has been one of the basic factors in manufacturing and control fields,
      and ultrasonic distance sensors have been widely used as a low-cost measuring
      tool. However, the propagation of ultrasonic waves is greatly affected by
      environmental factors such as temperature, humidity and atmospheric pressure. In
      order to solve the problem of inaccurate measurement, which is significant within
      industry, this paper presents a novel ultrasonic distance sensor model using
      networked error correction (NEC) trained on experimental data. This is more
      accurate than other existing approaches because it uses information from indirect
      association with neighboring sensors, which has not been considered before. The
      NEC technique, focusing on optimization of the relationship of the topological
      structure of sensor arrays, is implemented for the compensation of erroneous
      measurements caused by the environment. We apply the maximum likelihood method to
      determine the optimal fusion data set and use a neighbor discovery algorithm to
      identify neighbor nodes at the top speed. Furthermore, we adopt the NEC
      optimization algorithm, which takes full advantage of the correlation
      coefficients for neighbor sensors. The experimental results demonstrate that the
      ranging errors of the NEC system are within 2.20%; furthermore, the mean absolute
      percentage error is reduced to 0.01% after three iterations of this method, which
      means that the proposed method performs extremely well. The optimized method of
      distance measurement we propose, with the capability of NEC, would bring a
      significant advantage for intelligent industrial automation. 

PMID- 24013492
TI  - Anthracene-bisphosphonate based novel fluorescent organic nanoparticles explored
      as apoptosis inducers of cancer cells.
AB  - We report the first synthesis and use of a well defined fluorescent organic
      nanoparticle (FON), tetraethyl anthracene-9,10-diyl-9,10-bis(phosphonate)
      [TEABP], as a selective anticancer candidate by apoptosis mediated cancer therapy
      towards U937 cells together with its unique solvatochromic properties. 

PMID- 24013494
TI  - Performance and characterization of a Pt-Sn(oxidized)/C cathode catalyst with a
      SnO2-decorated Pt3Sn nanostructure for oxygen reduction reaction in a polymer
      electrolyte fuel cell.
AB  - We have prepared and characterized a SnO2-decorated Pt-Sn(oxidized)/C cathode
      catalyst in a polymer electrolyte fuel cell (PEFC). Oxygen reduction reaction
      (ORR) performance of Pt/C (TEC10E50E) remained almost unchanged or even tended to
      reduce in repeated I-V load cycles, whereas the I-V load performance of the Pt
      Sn(oxidized)/C prepared by controlled oxidation of a Pt-Sn alloy/C sample with
      the Pt3Sn phase revealed a significant increase with increasing I-V load cycles.
      The unique increase in the ORR performance of the Pt-Sn(oxidized)/C catalyst was
      ascribed to a promoting effect of SnO2 nano-islands formed on the surface of
      Pt3Sn core nanoparticles. Also in a rotating disk electrode (RDE) setup, the mass
      activity of an oxidized Pt3Sn/C catalyst was initially much lower than that of a
      Pt/C catalyst, but it increased remarkably after 5000 rectangular durability
      cycles and became higher than that of the fresh Pt/C. The maximum power density
      per electrochemical surface area for the Pt-Sn(oxidized)/C catalyst in a PEFC was
      about 5 times higher than that for the Pt/C catalyst at 0.1-0.8 A cm(-2) of the
      current density. In situ X-ray absorption near-edge structure (XANES) analysis at
      the Pt LIII-edge in increasing/decreasing potential operations and at the Sn K
      edge in the I-V load cycles revealed a remarkable suppression of Pt oxidation
      compared with the Pt/C catalyst at higher potentials and no change in the Sn
      oxidation state, respectively, resulting in higher performance and stability of
      the Pt-Sn(oxidized)/C catalyst due to the SnO2 nano-islands under the PEFC
      operation conditions. The SnO2 nano-island decorated Pt-Sn(oxidized)/C catalyst
      with a Pt3Sn alloy nanostructure is regarded as a promising candidate for a PEFC
      cathode catalyst. 

PMID- 24013493
TI  - Ongoing contact activation in patients with hereditary angioedema.
AB  - Hereditary angioedema (HAE) is predominantly caused by a deficiency in C1
      esterase inhibitor (C1INH) (HAE-C1INH). C1INH inhibits activated factor XII
      (FXIIa), activated factor XI (FXIa), and kallikrein. In HAE-C1INH patients the
      thrombotic risk is not increased even though activation of the contact system is
      poorly regulated. Therefore, we hypothesized that contact activation
      preferentially leads to kallikrein formation and less to activation of the
      coagulation cascade in HAE-C1INH patients. We measured the levels of C1INH in
      complex with activated contact factors in plasma samples of HAE-C1INH patients
      (N=30, 17 during remission and 13 during acute attack) and healthy controls
      (N=10). We did not detect differences in enzyme-inhibitor complexes between
      samples of controls, patients during remission and patients during an acute
      attack. Reconstitution with C1INH did not change this result. Next, we determined
      the potential to form enzyme-inhibitory complexes after complete in vitro
      activation of the plasma samples with a FXII trigger. In all samples, enzyme
      C1INH levels increased after activation even in patients during an acute attack.
      However, the levels of FXIIa-C1INH, FXIa-C1INH and kallikrein-C1INH were at least
      52% lower in samples taken during remission and 70% lower in samples taken during
      attack compared to samples from controls (p<0.05). Addition of C1INH after
      activation led to an increase in levels of FXIIa-C1INH and FXIa-C1INH (p<0.05),
      which were still lower than in controls (p<0.05), while the levels of kallikrein
      C1INH did not change. These results are consistent with constitutive activation
      and attenuated depletion of the contact system and show that the ongoing
      activation of the contact system, which is present in HAE-C1INH patients both
      during remission and during acute attacks, is not associated with preferential
      generation of kallikrein over FXIa. 

PMID- 24013495
TI  - PET-CT evaluation of solitary pulmonary nodules: correlation with maximum
      standardized uptake value and pathology.
AB  - PURPOSE: 18-fluorine fluorodeoxyglucose ((18)F-FDG) positron emission tomography
      computed tomography (PET-CT) has an established role for the characterization of
      solitary pulmonary nodules (SPN). Visual assessment of nodule morphology,
      together with maximum standardized uptake value (SUVmax), is used to estimate
      likelihood of malignancy. We correlated SUVmax value with pathology of SPN and
      assessed diagnostic accuracy in differentiating malignant from benign nodule,
      using 2.5 as threshold SUVmax. METHODS: Retrospective review of PET-CT scans for
      SPN characterization between April 2008 and June 2011 was performed. Only cases
      with pathological verification were included. RESULTS: A total of 641 PET-CTs
      were performed for SPN characterization and staging; 186 patients (77 males, 109
      females) with pathological confirmation were included, and 158 (85 %) nodules
      were malignant: adenocarcinomas (n = 66), squamous cell carcinomas (n = 40), and
      metastases (n = 20) were the commonest. 28 lesions (15 %) were benign, including
      granuloma/chronic inflammation (n = 8), infection (n = 7), and hamartomas (n =
      5). Using cutoff SUVmax of 2.5, the accuracy of PET-CT in diagnosing malignant
      SPN is 81.2 %, with sensitivity 86.7 %, specificity 50 %, PPV 90.7 %, and NPV 40
      %. The likelihood of malignancy increases with SUVmax. Nevertheless, even with
      SUVmax <2.5, there is a 62 % chance that a nodule is malignant. CONCLUSIONS:
      Although PET-CT is useful in diagnostic workup of SPN, it cannot replace "gold
      standard" tissue diagnosis.

PMID- 24013496
TI  - Preparation of non-aggregating aqueous fullerenes in highly saline solutions with
      a biocompatible non-ionic polymer.
AB  - Size-tunable stable aqueous fullerenes were prepared with different
      concentrations of biocompatible block-copolymer pluronic (PA) F-127, ranging from
      0.001% to 1% (w/v). Size uniformity increased with the increase in PA
      concentration, yielding optimum 58.8 +/- 5.6 and 61.8 +/- 5.6 nm nC60s and nC70s,
      respectively (0.10%w/v PA), as observed using a dynamic light scattering
      technique. Fullerene aqueous suspensions also manifested enhanced stability in
      saline solution, Dulbecco's modified Eagle medium (DMEM), and Roswell Park
      Memorial Institute (RPMI) culture medium. Transmission electron microscopy was
      performed to elaborate on the morphology and size specificity of fullerene
      clusters. Physicochemical characterizations of the suspended fullerenes were
      performed through UV-vis spectroscopy and electrophoretic mobility measurements.
      PA molecules showed size restriction by encasement, as observed via molecular
      dynamics simulations. Such solubilization with controllable size and non
      aggregating behavior can facilitate application enhancement and mechanistic
      environmental and toxicological studies of size-specific fullerenes.

PMID- 24013497
TI  - The utility of the IGF-I generation test in children with chronic kidney disease.
AB  - BACKGROUND: To determine if the insulin-like-growth factor (IGF-I) generation
      test is a marker for growth hormone (GH) sensitivity in children with chronic
      kidney disease (CKD). METHODS: This was a randomized cross-over study in which
      children with CKD received low-dose (0.025 mg/kg/day) and high-dose (0.05
      mg/kg/day) GH therapy in the framework of a 7-day IGF-I generation test. Blood
      samples were collected on day 1 (D1; pre-dose) and on day 8 (D8; post 7 doses) of
      GH therapy. All subjects received GH for 12 months at 0.05 mg/kg/day. Serum IGF-I
      was measured by radioimmunometric assay. Normative historic data from healthy
      children and those with idiopathic short stature were used for comparison.
      RESULTS: Sixteen subjects (age 2-13 years) with creatinine clearances of between
      25 and 75 ml/min/1.73 m(2) were enrolled. Annualized height velocity for all
      subjects was 10.3 +/- 1.1 cm/year (mean +/- standard deviation), with an annual
      change in height Z score of 0.7 +/- 1.0. No correlation was found between the
      generated serum IGF-I levels (D8 - D1) and creatinine clearances, and with
      changes in height Z scores. Serum IGF-I levels on D1 and D8 in CKD subjects were
      lower than normative data, but with adequate IGF-I generation on D8. CONCLUSIONS:
      Children with CKD were able to respond to GH therapy with both growth and an
      increase in serum IGF-I levels, but the IGF-I generation test was not a good
      predictor of growth response in this cohort.

PMID- 24013498
TI  - Renal parenchymal thickness in children with solitary functioning kidney.
AB  - BACKGROUND: Reduced renal parenchymal thickness (PT) is a parameter used by
      clinicians to assess the degree of hydronephrosis. In patients with a congenital
      hydronephrotic solitary functioning kidney (SFK), PT is difficult to determine as
      there is no comparison with the contralateral kidney. The aim of this study was
      to obtain ultrasound measurements of PT in children with normal SFK and to
      compare these data with PT measurements in children with two functioning kidneys.
      METHODS: This was a prospective multicenter study carried out between 2006 and
      2011 in which 236 children aged 11 days to 18.96 years with healthy SFK were
      examined. The SFK etiologies were unilateral renal agenesis or a nonfunctioning
      contralateral kidney, mostly due to multicystic dysplasia. In addition to
      determining other parameters, we measured PT in the middle third of the kidney by
      ultrasound. Correlations between PT and age, height and weight were assessed.
      RESULTS: Correlation analysis showed a positive correlation with renal PT for all
      parameters. The correlation coefficients for age, height and weight were 0.863,
      0.873 and 0.874, respectively. In most age categories, the renal parenchyma was
      significantly thicker in the SFK than in two functioning kidneys. CONCLUSIONS:
      Based on our results, we suggest that PT in the SFK is correlated with height,
      weight and age of the patient. Consequently, measurements of PT may be used for
      monitoring the development of the healthy SFK and may contribute to a more
      accurate assessment of the severity of SFK anomalies.

PMID- 24013499
TI  - Physical clustering of FLC alleles during Polycomb-mediated epigenetic silencing
      in vernalization.
AB  - Vernalization, the promotion of flowering by cold, involves Polycomb-mediated
      epigenetic silencing of FLOWERING LOCUS C (FLC). Cold progressively promotes cell
      autonomous switching to a silenced state. Here, we used live-cell imaging of FLC
      lacO to monitor changes in nuclear organization during vernalization. FLC-lacO
      alleles physically cluster during the cold and generally remain so after plants
      are returned to warm. Clustering is dependent on the Polycomb trans-factors
      necessary for establishment of the FLC silenced state but not on LIKE
      HETEROCHROMATIN PROTEIN 1, which functions to maintain silencing. These data
      support the view that physical clustering may be a common feature of Polycomb
      mediated epigenetic switching mechanisms.

PMID- 24013500
TI  - A conserved ncRNA-binding protein recruits silencing factors to heterochromatin
      through an RNAi-independent mechanism.
AB  - Long noncoding RNAs (lncRNAs) can trigger repressive chromatin, but how they
      recruit silencing factors remains unclear. In Schizosaccharomyces pombe,
      heterochromatin assembly on transcribed noncoding pericentromeric repeats
      requires both RNAi and RNAi-independent mechanisms. In Saccharomyces cerevisiae,
      which lacks a repressive chromatin mark (H3K9me [methylated Lys9 on histone H3]),
      unstable ncRNAs are recognized by the RNA-binding protein Nrd1. We show that the
      S. pombe ortholog Seb1 is associated with pericentromeric lncRNAs. Individual
      mutation of dcr1+ (Dicer) or seb1+ results in equivalent partial reductions of
      pericentromeric H3K9me levels, but a double mutation eliminates this mark. Seb1
      functions independently of RNAi by recruiting the NuRD (nucleosome remodeling and
      deacetylase)-related chromatin-modifying complex SHREC (Snf2-HDAC [histone
      deacetylase] repressor complex).

PMID- 24013501
TI  - The C terminus of p53 regulates gene expression by multiple mechanisms in a
      target- and tissue-specific manner in vivo.
AB  - The p53 tumor suppressor is a transcription factor that mediates varied cellular
      responses. The C terminus of p53 is subjected to multiple and diverse post
      translational modifications. An attractive hypothesis is that differing sets of
      combinatorial modifications therein determine distinct cellular outcomes. To
      address this in vivo, a Trp53(DeltaCTD/DeltaCTD) mouse was generated in which the
      endogenous p53 is targeted and replaced with a truncated mutant lacking the C
      terminal 24 amino acids. These Trp53(DeltaCTD/DeltaCTD) mice die within 2 wk post
      partum with hematopoietic failure and impaired cerebellar development.
      Intriguingly, the C terminus acts via three distinct mechanisms to control p53
      dependent gene expression depending on the tissue. First, in the bone marrow and
      thymus, the C terminus dampens p53 activity. Increased senescence in the
      Trp53(DeltaCTD/DeltaCTD) bone marrow is accompanied by up-regulation of Cdkn1
      (p21). In the thymus, the C-terminal domain negatively regulates p53-dependent
      gene expression by inhibiting promoter occupancy. Here, the hyperactive
      p53(DeltaCTD) induces apoptosis via enhanced expression of the proapoptotic Bbc3
      (Puma) and Pmaip1 (Noxa). In the liver, a second mechanism prevails, since
      p53(DeltaCTD) has wild-type DNA binding but impaired gene expression. Thus, the C
      terminus of p53 is needed in liver cells at a step subsequent to DNA binding.
      Finally, in the spleen, the C terminus controls p53 protein levels, with the
      overexpressed p53(DeltaCTD) showing hyperactivity for gene expression. Thus, the
      C terminus of p53 regulates gene expression via multiple mechanisms depending on
      the tissue and target, and this leads to specific phenotypic effects in vivo. 

PMID- 24013502
TI  - Epe1 recruits BET family bromodomain protein Bdf2 to establish heterochromatin
      boundaries.
AB  - Heterochromatin spreading leads to the silencing of genes within its path, and
      boundary elements have evolved to constrain such spreading. In fission yeast,
      heterochromatin at centromeres I and III is flanked by inverted repeats termed
      IRCs, which are required for proper boundary functions. However, the mechanisms
      by which IRCs prevent heterochromatin spreading are unknown. Here, we identified
      Bdf2, which is homologous to the mammalian bromodomain and extraterminal (BET)
      family double bromodomain proteins involved in diverse types of cancers, as a
      factor required for proper boundary function at IRCs. Bdf2 is enriched at IRCs
      through its interaction with the boundary protein Epe1. The bromodomains of Bdf2
      recognize acetylated histone H4 tails and antagonize Sir2-mediated deacetylation
      of histone H4K16. Furthermore, abolishing H4K16 acetylation (H4K16ac) with an
      H4K16R mutation promotes heterochromatin spreading, and mimicking H4K16ac by an
      H4K16Q mutation blocks heterochromatin spreading at IRCs. Our results thus
      illustrate a mechanism of establishing chromosome boundaries at specific sites
      through the recruitment of a factor that protects euchromatic histone
      modifications. They also reveal a previously unappreciated function of H4K16ac in
      cooperation with H3K9 methylation to regulate heterochromatin spreading.

PMID- 24013503
TI  - Regulation of constitutive and alternative splicing by PRMT5 reveals a role for
      Mdm4 pre-mRNA in sensing defects in the spliceosomal machinery.
AB  - The tight control of gene expression at the level of both transcription and post
      transcriptional RNA processing is essential for mammalian development. We here
      investigate the role of protein arginine methyltransferase 5 (PRMT5), a putative
      splicing regulator and transcriptional cofactor, in mammalian development. We
      demonstrate that selective deletion of PRMT5 in neural stem/progenitor cells
      (NPCs) leads to postnatal death in mice. At the molecular level, the absence of
      PRMT5 results in reduced methylation of Sm proteins, aberrant constitutive
      splicing, and the alternative splicing of specific mRNAs with weak 5' donor
      sites. Intriguingly, the products of these mRNAs are, among others, several
      proteins regulating cell cycle progression. We identify Mdm4 as one of these key
      mRNAs that senses the defects in the spliceosomal machinery and transduces the
      signal to activate the p53 response, providing a mechanistic explanation of the
      phenotype observed in vivo. Our data demonstrate that PRMT5 is a master regulator
      of splicing in mammals and uncover a new role for the Mdm4 pre-mRNA, which could
      be exploited for anti-cancer therapy.

PMID- 24013504
TI  - Tpz1 controls a telomerase-nonextendible telomeric state and coordinates
      switching to an extendible state via Ccq1.
AB  - Telomeres are nucleoprotein complexes comprising telomeric DNA repeats bound by
      the multiprotein shelterin complex. A dynamic binary switch between telomerase
      extendible and telomerase-nonextendible telomeric states determines telomere
      length homeostasis. However, the molecular nature of the nonextendible state is
      largely unknown. Here, we show that, in fission yeast, Tpz1 (the ortholog of
      human TPP1)-mediated complete linkage within the shelterin complex, bridging
      telomeric dsDNA to ssDNA, controls the telomerase-nonextendible state. Disruption
      of this linkage leads to unregulated telomere elongation while still retaining
      the shelterin components on telomeres. Therefore, the linkage within the
      shelterin components, rather than the individual shelterin components per se,
      defines the telomerase-nonextendible state. Furthermore, epistasis analyses
      reveal that Tpz1 also participates in the activation of telomeres to the
      extendible state via its interaction with Ccq1. Our results suggest critical
      regulatory roles of Tpz1 in the telomere binary switch.

PMID- 24013505
TI  - Mutually exclusive signaling signatures define the hepatic and pancreatic
      progenitor cell lineage divergence.
AB  - Understanding how distinct cell types arise from multipotent progenitor cells is
      a major quest in stem cell biology. The liver and pancreas share many aspects of
      their early development and possibly originate from a common progenitor. However,
      how liver and pancreas cells diverge from a common endoderm progenitor population
      and adopt specific fates remains elusive. Using RNA sequencing (RNA-seq), we
      defined the molecular identity of liver and pancreas progenitors that were
      isolated from the mouse embryo at two time points, spanning the period when the
      lineage decision is made. The integration of temporal and spatial gene expression
      profiles unveiled mutually exclusive signaling signatures in hepatic and
      pancreatic progenitors. Importantly, we identified the noncanonical Wnt pathway
      as a potential developmental regulator of this fate decision and capable of
      inducing the pancreas program in endoderm and liver cells. Our study offers an
      unprecedented view of gene expression programs in liver and pancreas progenitors
      and forms the basis for formulating lineage-reprogramming strategies to convert
      adult hepatic cells into pancreatic cells.

PMID- 24013507
TI  - Expression profiling of Plasmodium berghei HSP70 genes for generation of bright
      red fluorescent parasites.
AB  - Live cell imaging of recombinant malarial parasites encoding fluorescent probes
      provides critical insights into parasite-host interactions and life cycle
      progression. In this study, we generated a red fluorescent line of the murine
      malarial parasite Plasmodium berghei. To allow constitutive and abundant
      expression of the mCherry protein we profiled expression of all members of the P.
      berghei heat shock protein 70 (HSP70) family. We identified PbHSP70/1, an
      invariant ortholog of Plasmodium falciparum HSP70-1, as the protein with the
      highest expression levels during Plasmodium blood, mosquito, and liver infection.
      Stable allelic insertion of a mCherry expression cassette into the PbHsp70/1
      locus created constitutive red fluorescent P. berghei lines, termed Pbred. We
      show that these parasites can be used for live imaging of infected host cells and
      organs, including hepatocytes, erythrocytes, and whole Anopheles mosquitoes.
      Quantification of the fluorescence intensity of several Pbred parasite stages
      revealed significantly enhanced signal intensities in comparison to GFP expressed
      under the control of the constitutive EF1alpha promoter. We propose that
      systematic transcript profiling permits generation of reporter parasites, such as
      the Pbred lines described herein. 

PMID- 24013508
TI  - Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the
      substrate in hypertension and ageing.
AB  - BACKGROUND: Both ageing and hypertension are known risk factors for atrial
      fibrillation (AF) although the pathophysiological contribution or interaction of
      the individual factors remains poorly understood. Here we aim to delineate the
      arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR).
      METHODS: SHR were studied at 12 and 15 months of age (n = 8 per group) together
      with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY).
      Electrophysiologic study was performed on superfused isolated right and left
      atrial preparations using a custom built high-density multiple-electrode array to
      determine effective refractory periods (ERP), atrial conduction and atrial
      arrhythmia inducibility. Tissue specimens were harvested for structural analysis.
      RESULTS: COMPARED TO WKY CONTROLS, THE SHR DEMONSTRATED: Higher systolic blood
      pressure (p<0.0001), bi-atrial enlargement (p<0.05), bi-ventricular hypertrophy
      (p<0.05), lower atrial ERP (p = 0.008), increased atrial conduction heterogeneity
      (p = 0.001) and increased atrial interstitial fibrosis (p = 0.006) & CD68
      positive macrophages infiltration (p<0.0001). These changes resulted in higher
      atrial arrhythmia inducibility (p = 0.01) and longer induced AF episodes (p =
      0.02) in 15-month old SHR. Ageing contributed to incremental bi-atrial
      hypertrophy (p<0.01) and atrial conduction heterogeneity (p<0.01) without
      affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of
      ageing on the atrial substrate may be secondary to the reduction in CD68-positive
      macrophages. CONCLUSIONS: Significant atrial electrical and structural remodeling
      is evident in the ageing spontaneously hypertensive rat atria. Concomitant
      hypertension appears to play a greater pathophysiological role than ageing
      despite their compounding effect on the atrial substrate. Inflammation is
      pathophysiologically linked to the pro-fibrotic changes in the hypertensive
      atria.

PMID- 24013509
TI  - Evaluation of asymptomatic venous disease by venous Doppler ultrasonography in
      patients with Behcet's disease without overt thrombosis.
AB  - One of the major causes of mortality and morbidity in Behcet's disease (BD) is
      vascular involvement. Limited data suggest a high prevalence of venous
      insufficiency (VI) and some cases of asymptomatic thrombosis in BD. In this
      study, we aimed to investigate asymptomatic venous disease by venous Doppler
      ultrasonography (US) prospectively in patients with BD, without known vascular
      disease. The study included 93 patients with BD (M/F, 45/48; age, 36.4 +/- 10
      years), 97 patients with ankylosing spondylitis (AS) (M/F, 50/47; age, 37.5 +/-
      9.5 years), and 43 healthy controls (HC) (M/F, 25/18; age, 34.7 +/- 4.5 years).
      All patients were examined for the clinical findings of venous thrombosis.
      Vessels of both upper and lower extremities were examined, while the subjects
      were in supine position by venous Doppler US. Clinical signs ("C"), the various
      etiologies ("E"), anatomical sites ("A"), and pathophysiological disorder ("P")
      (CEAP) severity score was used to evaluate the severity of the VI. We did not
      detect any "silent thrombosis" in any group. VI findings in lower extremity were
      detected in 32.2 % (n = 30) in the BD group, 28.8 % (n = 28) in AS group, and 9.3
      % (n = 4) in the HC group. Both BD and AS patients had significantly higher VI
      rates than controls (p = 0.007 and 0.015). Similarly, CEAP severity score in BD
      (0.34 (0-3)) was significantly higher than controls (0, p = 0.008) but similar to
      AS (0.18 (0-39), p = 0.18). No correlations were present between C-reactive
      protein elevation (>5 mg/L) and VI in both BD (p = 0.546) and AS (p = 0.754). A
      high prevalence of VI was present in both BD and AS patients without symptomatic
      thrombosis. Presence of VI also in AS, a disease without a major tendency to
      venous thrombosis, might suggest that chronic inflammation might cause a mild
      insufficiency detected only by Power US in venous vessels. Long-term consequences
      of this finding require further follow-up studies to show whether asymptomatic
      venous disease is a predictor of future venous thrombotic events in patients with
      BD.

PMID- 24013510
TI  - Circulating tumor cells and brain metastasis outcome in patients with HER2
      positive breast cancer: the LANDSCAPE trial.
AB  - BACKGROUND: Decrease of circulating tumor cells (CTC) during treatment is an
      independent prognostic factor in metastatic breast cancer (MBC). We specifically
      evaluated the impact of CTC on brain metastasis outcome. METHODS: HER2-positive
      MBC with brain metastasis not previously treated with whole-brain radiotherapy
      received first-line combination of lapatinib and capecitabine in a phase II
      study. CTC were detected at baseline and day 21 (CellSearch). RESULTS: Median
      follow-up of the 44 analyzed patients was 21.2 months. The central nervous system
      objective response (CNS-OR) rate was 66%. At baseline, 20 of 41 assessable
      patients for CTC (49%) had >=1 CTC (range 1-301, median 3) and 9 (22%) had >=5
      CTC. At day 21, 7 of 38 patients (18%) had >=1 CTC (P = 0.006, versus baseline),
      and CTC had disappeared in 11 patients. CNS-OR rate was significantly higher in
      patients with no CTC at day 21 [25 of 31 (80%) versus 2 of 7 (29%), P = 0.01].
      The 1-year overall survival rate was 83.9% in patients with no CTC at day 21
      versus 42.9% in patients with >=1 CTC (P = 0.02). CONCLUSIONS: This is the first
      report showing a correlation between CNS metastasis response, outcome and early
      CTC clearance under targeted treatment of HER2+ MBC. CLINICAL TRIALS NUMBER:
      NCT00967031.

PMID- 24013511
TI  - Time to first cigarette and lung cancer risk in Japan.
AB  - BACKGROUND: Cigarette smoking is the major cause of lung cancer (LC). Although
      the time to first cigarette (TTFC) of the day is a distinct indicator of nicotine
      dependence, little information is available on its possible relation to LC.
      PATIENTS AND METHODS: This case-control study includes a total of 1572 incident
      LC cases and 1572 non-cancer controls visiting for the first time the Aichi
      Cancer Center Hospital between 2001 and 2005. We estimated the odds ratio (OR)
      and 95% confidence interval (CI) for TTFC using a logistic regression model after
      adjustment for several potential confounders. RESULTS: TTFC was inversely
      associated with the risk of LC. This association was consistent across
      histological subtypes of LC. For all LCs considered among ever smokers and after
      accurate allowance for smoking quantity and duration, besides other relevant
      covariates, compared with TTFC >60 min, the adjusted ORs were 1.08 (95% CI, 0.73
      1.61) for TTFC of 31-60 min, 1.40 (0.98-2.01) for 6-30 min and 1.86 (1.28-2.71)
      for within 5 min (Ptrend, < 0.001). Statistically marginally significant
      heterogeneity by histological subtype was observed (Pheterogeneity, 0.002).
      CONCLUSIONS: Nicotine dependence, as indicated by the TTFC, is associated with
      increased risk of LC and is therefore an independent marker of exposure to
      tobacco smoking.

PMID- 24013512
TI  - Palliative radiotherapy and chemotherapy instead of surgery in symptomatic rectal
      cancer with synchronous unresectable metastases: a phase II study.
AB  - BACKGROUND: In stage IV rectal cancer, palliative surgery is often carried out
      upfront. This study investigated whether the surgery can be avoided. PATIENTS AND
      METHODS: Forty patients with symptomatic primary rectal adenocarcinoma and
      synchronous distant metastases deemed to be unresectable received 5 * 5 Gy
      irradiation and then oxaliplatin-based chemotherapy. Before treatment, 38% of
      patients had a near-obstructing lesion. The palliative effect was evaluated by
      questionnaires completed by the patients. RESULTS: The median follow-up for
      living patients was 26 months (range 19-34). The median overall survival was 11.5
      months. Eight patients (20%) required surgery during the course of their disease:
      seven patients required stoma creation and one had local excision. Thirty percent
      of patients had a complete resolution of pelvic symptoms during the whole course
      of the disease, and 35% had significant improvement. In the subgroup with a near
      obstructing lesion, 23% of patients required stoma creation. In all patients, the
      probability of requiring palliative surgery at 2 years was 17.5% [95% confidence
      interval (CI) 13% to 22%), and the probability of sustained good palliative
      effect after radiotherapy and chemotherapy was 67% (95% CI 58% to 76%).
      CONCLUSION: Short-course radiotherapy and chemotherapy allowed most patients to
      avoid surgery, even those with a near-obstructing lesion. CLINICALTRIALS: The
      trial is registered with ClinicalTrials.gov: number NCT01157806.

PMID- 24013513
TI  - Selenium content of Belgian cultivated soils and its uptake by field crops and
      vegetables.
AB  - A series of 695 food crops were collected on 539 soils throughout Belgium. All
      samples were collected on commercial production fields, omitting private gardens.
      All crops were analyzed for their selenium (Se) concentration. The soils
      represent different soil types occurring in Belgium, with soil textures ranging
      from sand to silt loam, and including a few clay soils. They were analyzed for Se
      concentration, organic carbon content, cation exchange capacity and extractable
      sulphur (S) concentration. The Se concentrations in the soils were low (range
      0.14-0.70 mg kg(-1) dw), but increasing soil Se concentrations were observed with
      increasing clay content. Stepwise multiple regressions were applied to determine
      relations between Se concentrations in crops and soil characteristics. Among
      field crops, wheat is the most important accumulator of selenium but the
      concentration remains rather low on the Belgian low Se-soils. Based on dry
      weight, leafy vegetables contain more Se than wheat. The soil is the most
      important source of Se and the element is transported with the water stream to
      the leaves, where it is accumulated. Vegetables rich in S, e.g. some Brassica and
      Allium species, have a higher capacity to accumulate Se as it can replace S in
      the proteins, although this accumulation is still limited at low soil Se
      concentrations. In loamy soils, weak correlations were found between the soil Se
      concentration and its concentration in wheat and potato. The uptake of Se
      increased with increasing pH. The Se concentrations in Belgian soils are far too
      low to generate a driving force on Se uptake. General climatic conditions such as
      temperature, air humidity and soil moisture are also important for the transfer
      of Se within the plant, and plant linked factors such as cultivar, growth stage
      and edible part are important as well, although their influence remains limited
      at low soil Se concentrations.

PMID- 24013514
TI  - Limited representation of drinking-water contaminants in pregnancy-birth cohorts.
AB  - Water contamination and noise have been consistently the least assessed
      environmental/lifestyle exposures in pregnancy-birth cohorts (PBC). Water quality
      surveillance data collected during the past decade within urban drinking-water
      distribution systems call for re-evaluation of water and health issues in the
      developed world. The objectives of this scientific commentary were to (i)
      highlight the extent of appraisal of water contamination in exposure assessment
      studies of PBC, worldwide, and (ii) propose recommendations to increase awareness
      of emerging water-related risks through their improved representation into PBC
      study designs in urban centers. Three scientific literature databases (Scopus,
      PubMed, and Web of Science) were used for a systematic search on worldwide PBC
      and their publications that considered water contamination and health outcomes.
      Publicly-available e-databases (ENRIECO, BIRTHCOHORTS, and CHICOS) were also
      employed for detailed exploration of existing European Union (EU)-based PBC. Out
      of the 76 PBC identified in the EU territory, only 12 of them incorporated water
      contamination into their study designs. Among which only 6 PBC published
      scientific articles that either included data on water contamination and/or water
      intake estimates. Trihalomethanes but not other disinfection by-products were
      mostly studied in the PBC around the globe, while fluoride, atrazine,
      perfluorinated compounds, tetrachloroethylene, and lead were studied to a lesser
      extent as water contaminants. It appears that chemical-based water contamination
      and corresponding human exposures represent a largely underappreciated niche of
      exposure science pertaining to pregnant mother and children's health in PBC.
      Future PBC studies should grasp this opportunity to substantially reform elements
      of water contamination in their exposure assessment protocols and effectively
      combine them with their epidemiological study designs. 

PMID- 24013515
TI  - The new face of the old molecules: crustin Pm4 and transglutaminase type I
      serving as rnps down-regulate astakine-mediated hematopoiesis.
AB  - Astakine is an important cytokine that is involved in crustacean hematopoiesis.
      Interestingly, the protein levels of astakine increased dramatically in plasma of
      LPS-injected shrimp while mRNA levels remained unchanged. Here, we investigated
      the involvement of astakine 3'-untranslated region (UTR) in its protein
      expression. The 3'-UTR of astakine down-regulated the expression of reporter
      protein but the mRNA stability of reporter gene was unaffected. We identified the
      functional regulatory elements of astakine 3'-UTR, where 3'-UTR242-483 acted as
      repressor. The electrophoresis mobility shift assay (EMSA), RNA pull-down assay
      and LC/MS/MS were performed to identify the protein association. We noted that
      crustin Pm4 and shrimp transglutaminase I (STG I) were associated to astakine 3'
      UTR242-483, while two other proteins have yet to be revealed. Depletion of
      hemocytic crustin Pm4 and STG I significantly increased the protein level of
      astakine while astakine mRNA level remained unaffected. Lipopolysaccharide (LPS)
      stimulated the secretion of crustin Pm4 and STG I from hemocytes to plasma and
      increased the astakine level to stimulate the hemocytes proliferation.
      Altogether, we identified the shrimp crustin Pm4 and STG I as novel RNA binding
      proteins that play an important role in down-regulating astakine expression at
      post-transcriptional level and are crucial for the maintenance of hematopoiesis. 

PMID- 24013516
TI  - Efficacy and safety of intermittent hemodialysis in infants and young children
      with inborn errors of metabolism.
AB  - BACKGROUND: Intermittent hemodialysis (IHD) is the most efficient form of renal
      replacement therapy (RRT) for removing toxic substances from patients' bodies.
      However, the efficacy and safety of IHD in infants and young children with inborn
      errors of metabolism are still not clear. METHODS: This retrospective study
      included patients with urea cycle disorders, maple syrup urine disease, and
      methylmalonic acidemia who received IHD or non-IHD RRT at our hospital between
      2001 and 2012 to remove ammonia, leucine, or methylmalonic acid. Both the
      efficacy and safety of the RRT were evaluated. RESULTS: Thirty-five courses of
      RRT, including 25 courses of IHD and ten courses of non-IHD RRT, for 15 patients
      were included in the analysis. Before 2006, non-IHD RRT procedures, including
      peritoneal dialysis (PD) and continuous venous-venous hemofiltration (CVVH), were
      the most often used; from 2006 onwards IHD was used. There was one procedure
      unrelated death. Catheter penetration occurred in one course of IHD. The efficacy
      data revealed that both the median duration of dialysis and the median 50 % toxin
      reduction time were shorter in IHD than in non-IHD RRT. CONCLUSIONS: In infants
      and young children with inborn errors of metabolism, IHD is safe and more
      efficient than non-IHD RRT at removing toxins.

PMID- 24013518
TI  - Coherent Stern-Gerlach momentum splitting on an atom chip.
AB  - In the Stern-Gerlach effect, a magnetic field gradient splits particles into
      spatially separated paths according to their spin projection. The idea of
      exploiting this effect for creating coherent momentum superpositions for matter
      wave interferometry appeared shortly after its discovery, almost a century ago,
      but was judged to be far beyond practical reach. Here we demonstrate a viable
      version of this idea. Our scheme uses pulsed magnetic field gradients, generated
      by currents in an atom chip wire, and radio-frequency Rabi transitions between
      Zeeman sublevels. We transform an atomic Bose-Einstein condensate into a
      superposition of spatially separated propagating wavepackets and observe spatial
      interference fringes with a measurable phase repeatability. The method is
      versatile in its range of momentum transfer and the different available splitting
      geometries. These features make our method a good candidate for supporting a
      variety of future applications and fundamental studies. 

PMID- 24013517
TI  - Association between use of benzodiazepines and risk of fractures: a meta
      analysis.
AB  - Benzodiazepines (BZDs) are some of the most commonly prescribed drugs in the
      world. It has been shown that BZD use could be associated with increased fracture
      risk. However, studies on the use of BZDs and fracture risk have yielded
      inconsistent results. Results from the present meta-analysis show that BZD use is
      associated with a moderate and clinically significant increase in the risk of
      fractures. INTRODUCTION: The relationship between the use of BZDs and fracture
      risk has been neither well identified nor summarized. This meta-analysis reports
      on the use of BZDs, especially short-acting BZDs, and their correlation with a
      moderate and clinically significant increase in fracture risk. This analysis will
      provide evidence for clinicians to consider fracture risk when prescribing BZDs
      among the elderly population. This study was conducted to determine whether
      people who take BZDs are at an increased fracture risk. METHODS: A systematic
      search of studies published through January 2013 was conducted using MEDLINE,
      EMBASE, OVID, and ScienceDirect. Case-control and cohort studies that assessed
      the relationship between BZD use and the risk of fractures were identified.
      Literature searches, study selections, methodological assessments, and data
      mining were independently conducted by two reviewers. Disagreements were resolved
      by consensus. STATA 12.0 software was used for the meta-analysis. Random effects
      models were used for pooled analysis due to heterogeneity among the studies.
      RESULTS: There were 25 studies, including 19 case-control studies and 6 cohort
      studies, that met the inclusion criteria. Overall, the results of the meta
      analysis indicated that BZD use was associated with a significantly increased
      fracture risk (relative risk (RR) = 1.25; 95% confidence intervals (CI), 1.17
      1.34; p < 0.001). Increased fracture risk associated with BZD use was observed in
      participants aged >=65 years old (RR = 1.26; 95% CI, 1.15-1.38; p < 0.001). When
      only hip fractures were included as the outcome measure, the RR increased to
      1.35. However, subgroup meta-analyses showed that there was no significant
      association between BZD use and fracture risk in Eastern countries (RR = 1.27;
      95% CI, 0.76-2.14; p = 0.362) as well as between long-acting BZD use and risk of
      fractures (RR = 1.21; 95% CI, 0.95-1.54; p = 0.12). After accounting for
      publication bias, we observed that the overall association between BZD use and
      fracture risk to be slightly weaker (RR = 1.21; 95% CI, 1.13-1.30) but still
      significant. CONCLUSION: The results of this meta-analysis demonstrate that the
      use of BZD, especially short-acting BZD, is associated with a moderate and
      clinically significant increase in fracture risk. However, large prospective
      studies that minimize selection bias are necessary to determine a more accurate
      fracture risk associated with BZD use.

PMID- 24013519
TI  - A mixed-type autoimmune hemolytic anemia with immune thrombocytopenia related
      with myositis and post-transplantation lymphoproliferative disorder.

PMID- 24013520
TI  - Bcl-2 expression is associated with poor prognosis of solitary plasmacytoma of
      bone.
AB  - Solitary plasmacytoma of bone (SPB) is a rare tumor that represents a minority of
      patients with plasma cell localized malignancy characterized by a single
      osteolytic bone lesion. The molecular mechanism underlying the genesis of SPB has
      remained enigmatic. Signal transducers and activators of transcription-3 (STAT3)
      is often activated in human cancers and is implicated in tumorigenesis. In the
      present work, the immunohistochemical expression of pSTAT3 (the active isoform of
      STAT3) and its potential downstream mediators (Bcl-2, Bcl-xL, c-Myc, cyclin D1,
      VEGF, cIAP-2, Mcl-1, and survivin) were examined, clinical features were
      investigated, and relative prognostic factors were analyzed. Positive expression
      of Bcl-2 was observed in 46.7 % (14/30) of patients, c-Myc in 36.7 % (11/30), and
      cyclin D1 in 23.3 % (7/30). By univariate analysis, Bcl-2 expression was found to
      be closely associated with shorter overall survival (OS) and progression-free
      survival. Bcl-2 and c-Myc positive expression were also found to be a factor that
      affect time to progression to multiple myeloma. In conclusion, results showed Bcl
      2 expression to be a clinically significant prognostic indicator for SPB patients
      and constitutive activated STAT3 may not be the sole primary regulatory
      mechanism. 

PMID- 24013521
TI  - Tuning Fluorescence Direction with Plasmonic Metal-Dielectric- Metal Substrates.
AB  - : Controlling the emission properties of fluorophores is essential for improving
      the performance of fluorescence-based techniques in modern biochemical research,
      medical diagnosis, and sensing. Fluorescence emission is isotropic in nature,
      which makes it difficult to capture more than a small fraction of the total
      emission. Metal- dielectric-metal (MDM) substrates, discussed in this Letter,
      convert isotropic fluorescence into beaming emission normal to the substrate.
      This improves fluorescence collection efficiency and also opens up new avenues
      for a wide range of fluorescence-based applications. We suggest that MDM
      substrates can be readily adapted for multiple uses, such as in microarray
      formats, for directional fluorescence studies of multiple probes or for molecule
      specific sensing with a high degree of spatial control over the fluorescence
      emission. SECTION: Physical Processes in Nanomaterials and Nanostructures.

PMID- 24013522
TI  - The impact of system of care support in adherence to wraparound principles in
      Child and Family Teams in child welfare in North Carolina.
AB  - North Carolina is one of a growing number of states to implement family meeting
      models in child welfare as a way to engage families, while simultaneously
      addressing complex familial needs and child safety issues. However, much is still
      unknown regarding how family meetings actually operate in child welfare,
      underscoring a clear need for further evaluation of this process. Utilizing
      direct observational data of Child and Family Team (CFT) meetings, collected as
      part of two separate evaluations of the North Carolina Division of Social
      Service's Multiple Response System (MRS) and System of Care (SOC) initiatives,
      the purpose of the current study was to examine whether the support provided by
      SOC improved fidelity to the CFT model in child welfare. The observations were
      conducted using the Team Observation Measure consisting of 78 indicators that
      measure adherence to ten domains associated with high quality family team
      meetings (e.g., collaborative, individualized, natural supports, outcomes based,
      strengths-based). Findings indicate that receiving SOC support in child welfare
      leads to a more collaborative and individualized decision-making process with
      families. Meeting facilitators in SOC counties were better prepared for CFTs, and
      had greater ability to lead a more robust and creative brainstorming process to
      develop a family-driven case plan. The current study also provides a much needed
      description of the CFT meeting process within child welfare using a direct
      observational measure.

PMID- 24013523
TI  - The mongoose, the pheasant, the pox, and the retrovirus.
AB  - Paleovirology is the study of ancient viruses. The existence of a paleovirus can
      sometimes be detected by virtue of its accidental insertion into the germline of
      different animal species, which allows one to date when the virus actually
      existed. However, the ancient and the modern often connect, as modern viruses
      have unexpected origins that can be traced to ancient infections. The genomes of
      two species of mongooses and an egg-laying mammal called an echidna show that a
      virus currently present in poultry, the reticuloendotheliosis virus (REV), is
      actually of ancient exotic mammalian origin. REV apparently spread to poultry
      through a circuitous route involving the isolation of malaria parasites from a
      pheasant from Borneo housed at the Bronx Zoo that was contaminated with REV.
      Repeated passage of this virus in poultry adapted the virus to its new host. At
      some point, the virus got inserted into another virus, called fowlpox virus,
      which has spread back into the wild. Although REV may still exist somewhere in a
      mammalian host, its modern form links an 8 million-year-old infection of the
      ancestor of a mongoose to a virus that now is circulating in wild birds through
      malaria studies in the mid-20(th) century. These lessons of ancient and modern
      viruses have implications for modern human pandemics from viral reservoirs and
      for human interventions that may come with unintended consequences.

PMID- 24013525
TI  - The effect of intra-articular injection of betamethasone acetate/betamethasone
      sodium phosphate at the knee joint on the hypothalamic-pituitary-adrenal axis: a
      case-controlled study.
AB  - BACKGROUND: Intra-articular corticosteroid injection (IACI) of betamethasone
      depot preparation is a popular procedure at the knee joint. Intra-articular
      corticosteroid injection in general could be associated with systemic effects
      including suppression of the hypothalamic-pituitary-adrenal axis. There are
      nearly no reports on the effect of IACI of betamethasone at the knee joint on the
      hypothalamic-pituitary-adrenal axis. METHOD: Consecutive patients attending the
      rheumatology or orthopedic clinic with osteoarthritic knee pain who were not
      responding satisfactorily to medical and physical therapy were allocated to group
      1 after consent and given IACI of 6 mg of betamethasone acetate/betamethasone
      sodium phosphate. After completion of this part, consecutive age- and sex-matched
      patients were allocated to group 2 and given intra-articular injection of 60 mg
      of sodium hyaluronate. Demographic, clinical, laboratory, and radiographic
      variables were documented. Just before the knee injection and 1, 2, 3, 4, and 8
      weeks later, patients had 1-MUg adrenocorticotropin hormone (ACTH) stimulation
      test. Secondary adrenal insufficiency (SAI) was defined as levels of less than 18
      ug/dL and lack of a rise of more than 6 ug/dL in serum cortisol level, 30 minutes
      after the ACTH stimulation test.Patients were blinded to the injected material,
      and all injections were ultrasound guided. RESULTS: Twenty patients were enrolled
      in each group and equally divided between the 2 sexes. The mean age of the
      patients was approximately 54 years in both groups. No significant difference in
      any variable was seen between the 2 groups. One patient only from group 1 (the
      betamethasone group) had SAI 3 weeks after the IACI compared to none in the
      control group (P > 0.9999). His serum cortisol level 30 minutes after the ACTH
      stimulation was 17 ug/dL, with a rise of 3 ug/dL from baseline. CONCLUSION: Intra
      articular corticosteroid injection of 6 mg of betamethasone acetate/betamethasone
      sodium phosphate at the knee joint was not significantly associated with SAI at
      the time points tested.

PMID- 24013524
TI  - Cohesin removal precedes topoisomerase IIalpha-dependent decatenation at
      centromeres in male mammalian meiosis II.
AB  - Sister chromatid cohesion is regulated by cohesin complexes and topoisomerase
      IIalpha. Although relevant studies have shed some light on the relationship
      between these two mechanisms of cohesion during mammalian mitosis, their
      interplay during mammalian meiosis remains unknown. In the present study, we have
      studied the dynamics of topoisomerase IIalpha in relation to that of the cohesin
      subunits RAD21 and REC8, the shugoshin-like 2 (Schizosaccharomyces pombe) (SGOL2)
      and the polo-like kinase 1-interacting checkpoint helicase (PICH), during both
      male mouse meiotic divisions. Our results strikingly show that topoisomerase
      IIalpha appears at stretched strands connecting the sister kinetochores of
      segregating early anaphase II chromatids, once the cohesin complexes have been
      removed from the centromeres. Moreover, the number and length of these
      topoisomerase IIalpha-connecting strands increase between lagging chromatids at
      anaphase II after the chemical inhibition of the enzymatic activity of
      topoisomerase IIalpha by etoposide. Our results also show that the etoposide
      induced inhibition of topoisomerase IIalpha is not able to rescue the loss of
      centromere cohesion promoted by the absence of the shugoshin SGOL2 during
      anaphase I. Taking into account our results, we propose a two-step model for the
      sequential release of centromeric cohesion during male mammalian meiosis II. We
      suggest that the cohesin removal is a prerequisite for the posterior
      topoisomerase IIalpha-mediated resolution of persisting catenations between
      segregating chromatids during anaphase II. 

PMID- 24013526
TI  - A postmarketing surveillance study on erbitux (cetuximab) in patients with
      metastatic colorectal cancer refractory to irinotecan-containing treatment.
AB  - OBJECTIVE: This postmarketing surveillance study evaluated the safety and
      efficacy of cetuximab therapy in patients with epidermal growth factor receptor
      (EGFR)-expressing metastatic colorectal cancer (mCRC) in Taiwan. METHODS:
      Patients with EGFR-expressing mCRC who had failed prior irinotecan-based
      chemotherapy and were receiving cetuximab therapy were monitored for treatment
      efficacy and safety from the time of first infusion until 28 days after the last
      infusion regardless of the reasons fordiscontinuation. The study followed 269
      patients for approximately 2 years. RESULTS: No unexpected adverse events
      associated with cetuximab therapy were reported, and most events were grade 1 or
      2. The most common drug-related adverse events of any grade were rash (21.6%) and
      dermatitis acneiform (4.8%). Reported grade 3/4 events were rash (4.5%),
      dermatitis acneiform (0.4%), and diarrhea (0.4%). Cetuximab treatment for
      patients receiving second-/third-line (177 patients) or above therapy (92
      patients) was associated with a median progression-free survival time of 3.37 and
      3.90 months, respectively, and a median overall survival time of 17.6 and 21.1
      months, respectively. The response rates for the second-/third-line treatment and
      fourth-line or above cetuximab treatment groups were similar (21.5% vs 17.4%; P =
      0.428). CONCLUSION: Cetuximab showed no unexpected safety findings and was
      efficacious in treating patients with EGFR-expressing mCRC in community practice
      in Taiwan.

PMID- 24013527
TI  - A Au-functionalized ZnO nanowire gas sensor for detection of benzene and toluene.
AB  - A novel sensing hybrid-material of Au nanoparticles (Au NPs)-functionalized ZnO
      nanowires (Au-ZnO NWs) was successfully synthesized by a two-stage solution
      process. First, ZnO NWs were fabricated via a low-temperature one-pot
      hydrothermal method with SDSN introduced as a structure-directing agent.
      Afterward, the as-prepared ZnO NWs were used as supports to load Au NPs with
      small sizes via precipitating HAuCl4 aqueous solution with ammonia. The obtained
      samples were characterized by means of XRD, SEM, TEM and EDX. Both pristine and
      Au-ZnO NWs were practically applied as gas sensors to compare the effect of Au
      NPs on the sensing performances and the obtained results demonstrated that after
      functionalization by catalytic Au NPs, the hybrid sensor exhibited not only
      faster response and recovery speeds but also a higher response to benzene and
      toluene than the pristine ZnO sensor at 340  degrees C, especially showing high
      selectivity and long-term stability for low concentration toluene, which is
      rarely reported with this method, indicating its original sensor application in
      detecting benzene and toluene. To interpret the enhanced gas sensing mechanism,
      the strong spillover effect of the Au NPs and the increased Schottky barriers
      caused by the electronic interaction between Au NPs and ZnO NW support are
      believed to contribute to the improved sensor performance. 

PMID- 24013529
TI  - Facile synthesis of graphene on dielectric surfaces using a two-temperature
      reactor CVD system.
AB  - Direct deposition of graphene on a dielectric substrate is demonstrated using a
      chemical vapor deposition system with a two-temperature reactor. The two
      temperature reactor is utilized to offer sufficient, well-proportioned floating
      Cu atoms and to provide a temperature gradient for facile synthesis of graphene
      on dielectric surfaces. The evaporated Cu atoms catalyze the reaction in the
      presented method. C atoms and Cu atoms respectively act as the nuclei for forming
      graphene film in the low-temperature zone and the zones close to the high
      temperature zones. A uniform and high-quality graphene film is formed in an
      atmosphere of sufficient and well-proportioned floating Cu atoms. Raman
      spectroscopy, scanning electron microscopy and atomic force microscopy confirm
      the presence of uniform and high-quality graphene. 

PMID- 24013528
TI  - Fractionated stereotactic radiotherapy in the treatment of pituitary adenomas.
AB  - PURPOSE: The purpose of this work was to evaluate tumor control and side effects
      associated with fractionated stereotactic radiotherapy (FSRT) in the management
      of residual or recurrent pituitary adenomas. PATIENTS AND METHODS: We report on
      37 consecutive patients with pituitary adenomas treated with FSRT at our
      department. All patients had previously undergone surgery. Twenty-nine patients
      had nonfunctioning, 8 had hormone-producing adenoma. The mean total dose
      delivered by a linear accelerator was 49.4 Gy (range 45-52.2 Gy), 5 * 1.8 Gy
      weekly. The mean PTV was 22.8 ccm (range 2.0-78.3 ccm). Evaluation included
      serial imaging tests, endocrinologic and ophthalmologic examination. RESULTS:
      Tumor control was 91.9 % for a median follow-up time of 57 months (range 2-111
      months). Before FSRT partial hypopituitarism was present in 41 % of patients,
      while 35 % had anterior panhypopituitarism. After FSRT pituitary function
      remained normal in 22 %, 43 % had partial pituitary dysfunction, and 35 % had
      anterior panhypopituitarism. Visual acuity was stable in 76 % of patients,
      improved in 19 %, and deteriorated in 5 %. Visual fields remained stable in 35
      patients (95 %), improved in one and worsened in 1 patient (2.7 %). CONCLUSION:
      FSRT is an effective and safe treatment for recurrent or residual pituitary
      adenoma. Good local tumor control and preservation of adjacent structures can be
      reached, even for large tumors.

PMID- 24013530
TI  - Innovative technologies for SFA management.

PMID- 24013531
TI  - Superficial femoral artery TASC D Registry: twelve-month effectiveness analysis
      of the Pulsar-18 SE nitinol stent in patients with critical limb ischemia.
AB  - AIM: Single center observational study analyzing the primary patency rate and
      freedom from target lesions revascularization rate of the Pulsar-18 nitinol stent
      after recanalization of long superficial femoral artery (SFA) occlusions (TASC D)
      in 22 patients with critical limb ischemia (CLI). METHODS: Between 1/2011 and
      7/2011, 22 consecutive patients (9 male, 13 female) with chronic total occlusions
      (CTO) of the femoro-popliteal arteries presenting with CLI (17 patients with
      Rutherford 4 score, and 5 patients with Rutherford 5 score) were enrolled and
      successfully recanalized using the Pulsar-18 self-expanding (SE) nitinol stent
      (BIOTRONIK AG, Buelach, Switzerland). Primary patency at 12 months was defined as
      no binary restenosis (>50%) on Duplex ultrasound (PSVR<2.5) and respectively no
      target lesion revascularization performed within 12 months. The average lesion
      length of the treated femoro-popliteal segment was 315 mm. Performing spot
      stenting average stent length in all patients was 245 mm (minimal 215 mm, maximal
      315 mm). RESULTS: Technical success, with establishing an antegrade straight line
      flow to the foot through a reopened SFA, was achieved in all 22 patients.
      Subintimal and intraluminal recanalization techniques were used. Two patients
      with Rutherford 5 score had a minor amputation shortly after the recanalization
      procedure. All other patients had a complete wound healing of their lesions
      during a 6 month follow-up. After 12 month follow-up the primary patency rate of
      the Pulsar-18 SE nitinol stent was 77% with a per protocol restenosis in 5 of 22
      patients. Seventeen patients showed a walking capacity on treadmill test >300
      meters (Rutherford II). Two patients with a documented restenosis were
      Rutherford, these patients were treated conservatively. Three patients with
      restenosis and a Rutherford III score were scheduled for an endovascular target
      lesion revascularization leading to a freedom from target lesion
      revascularization rate of 86%. CONCLUSION: Endovascular intervention of long SFA
      occlusions using subintimal or intraluminal recanalization technique with
      implantation of the Pulsar-18 SE nitinol stent in CLI patients is safe and
      clinically effective with a primary patency rate after 12 months of 77% and a
      freedom from target lesion revascularization rate of 86%.

PMID- 24013532
TI  - Nitinol stents with polymer-free paclitaxel coating for stenosis of failing
      infrainguinal bypass grafts.
AB  - AIM: This study was designed to investigate the immediate and one-year outcomes
      of polymer-free paclitaxel coated drug-eluting stent (DES) implantation in a
      consecutive series of patients presenting with stenosis of infrainguinal bypass
      grafts. METHODS: Between January 2011 and January 2012, 11 patients with failing
      infrainguinal bypass grafts were treated in two institutions. Clinical status and
      Duplex scan parameters were recorded at baseline and over a follow-up period of
      one year. RESULTS: DES implantation was successfully performed in all patients.
      Ten patients received a single stent and one patient received two stents. At one
      year, one patient showed total bypass graft occlusion (9%). In all the remaining
      patients, Duplex scan examination documented patency of the treated grafts.
      CONCLUSION: DES implantation in failing infrainguinal bypass grafts can be safely
      performed and provides satisfactory clinical outcomes. The patency rate of 91%
      favourably compares with those obtained with other endovascular treatments such
      as plain balloon or cutting balloon angioplasty.

PMID- 24013533
TI  - The use of the GORE(r) TIGRIS(r) Vascular Stent with dual component design in the
      superficial femoral and popliteal arteries at 6 months.
AB  - AIM: The aim of this study was to collect procedural and clinical data assessing
      safety and performance of the GORE(r) TIGRIS(r) Vascular Stent, a novel dual
      component stent, made of a nitinol wire frame combined with a fluoropolymer
      interconnecting structure. METHODS: This retrospective analysis included 32
      consecutive patients (20 men, mean age 72.8 years) with 40 atherosclerotic
      femoropopliteal lesions (occlusions in 5%) who underwent angioplasty and
      implantation of a GORE(r) TIGRIS(r) Vascular Stent. The patients were scheduled
      for follow-up at 3, 6 and 12 months after stent implantation for Duplex
      ultrasound and assessment of Rutherford Becker class (RBC) and Ankle-Brachial
      Index (ABI) RESULTS: The mean implanted stent length was 62.3 mm (range 30-100
      mm). Procedural success (residual stenosis <30%) was achieved in 100% of the
      lesions. At 6 months 2 restenosis in 2 patients were observed, resulting in a
      cumulative primary patency rate (+/-standard error) of 91.7+/-8.0%. Between
      baseline and 6 months the ABI increased from 0.65+/-0.18 to 0.96+/-0.12
      (P<0.0001) and the median of RBC increased from 3 to 1.5 (P<0.0005). No stent
      thrombosis was found. CONCLUSION: In this retrospective collection of patients
      all lesions could be successfully treated with this novel hybrid TIGRIS stent.
      These preliminary results show promising primary patency rates at 6 months. In
      addition, significant improvements were observed in symptom classification and
      hemodynamics.

PMID- 24013534
TI  - Treating with an implant: BMS or DES?
AB  - As the minimal invasive procedures for the treatment of peripheral arterial
      disease grow at exponential rates, interventional radiologists and vascular
      surgeons are more often faced with the difficult decision of which devices are
      the most appropriate to bring the desired results. Under the light of the newest
      studies and always having in mind the concept of "leaving no metal behind", when
      focusing on the lesions within the superficial femoral artery and popliteal
      arteries, we try to answer the question: treating with an implant, bare metal
      stents or drug eluting stents? 

PMID- 24013535
TI  - Midterm results of the transarterial use of Onyx in the treatment of persisting
      type II endoleaks after EVAR.
AB  - AIM: Type II endoleaks with growing aneurysm sac >5 mm in diameter after EVAR
      require treatment. Different treatment options have been reported. The aim of
      this study was to evaluate the use of an ethylene-vinyl alcohol copolymer (Onyx)
      in an endovascular approach. METHODS: Between January 2010 and December 2011, 10
      consecutive patients with persistent type II endoleaks leading to aneurysm growth
      >5 mm were treated in our center by transarterial Onyx embolization by super
      selective cannulation of the endoleak with microcatheters. Technical success was
      defined as transarterial Onyx deployment directly into the aneurysm sac. Clinical
      success was defined as stable or shrinking axial aneurysmal diameter during
      follow- up using an angiographic computed tomography. RESULTS: Ten patients with
      13 persistent type II endoleaks leading to aneurysm sac growth of >5 mm were
      identified in the time period. Technical success was 92% (12/13 patients). Two
      patients underwent a staged procedure because several, unconnected type II
      endoleaks were present. In one patient a cannulation of the inflow vessel
      responsible for the endoleak was not possible, continued efforts led to a rupture
      of the hypogastric artery which was treated by covered stent implantation. In one
      patient an extravasation of onyx out of the aneurysm sac into the inferior vena
      cava during the embolization process made a transvenous goose snare maneuver
      necessary to retrieve the dislocated copolymer. No further complications were
      observed during the mean follow-up of 19.8 months (range, 3-31 months). In all
      patients with successful embolization the aneurysm sac remained stable or was
      decreased within the follow-up period. CONCLUSION: Use of Onyx in the
      endovascular treatment of type II endoleaks after EVAR is feasible, safe when
      accurately deployed and efficient. Further studies are necessary to evaluate the
      value of the different treatment modalities (translumbar vs. transarterial).

PMID- 24013536
TI  - Intervention for type II endoleaks? "Primum non nocere": appraisal for the
      conservative management of low-pressure endoleaks after endovascular aneurysm
      repair.
AB  - Endoleaks are the most common problem following endovascular aneurysm repair. The
      importance of a type II endoleak has often been subject of discussion in
      scientific literature. Conflicting data on the natural history of type II
      endoleak have been published. There is no consensus on the threshold for
      treatment of type II endoleak and controversy exists about the optimal treatment
      modality. This paper discusses the evidence behind treating type II endoleak and
      investigates the need for treatment. 

PMID- 24013537
TI  - Embolisation of type 2 endoleaks after endovascular aneurysm repair.
AB  - Endovascular treatment has become the preferred method of repair of abdominal and
      thoracic aortic aneurysms, and comes with a unique complication in the form of
      endoleaks (type I-IV). Type II endoleaks are the focus of this review. They are
      the most common form of endoleak detected in CT surveillance following
      endovascular repair. They are observed in 9% to 30% of patients after abdominal
      endovascular repair (EVR), and 1.4% following thoracic endovascular aortic repair
      (TEVR). They are classified as primary or secondary, depending on when they are
      identified following EVR. Typically, retrograde filling of the aneurysm sac is
      caused by single or multiple, patent feeding vessels. Despite its relative
      frequency, there is a lack of consensus on the threshold at which treatment
      should be considered. The aims of treatment are to halt sac expansion or to
      prevent rupture. A majority of patients may be managed conservatively. In those
      that are treated, the most common form of management is single vessel
      embolization. As we will discuss here, there are several ways of performing this
      procedure, based on the site of endoleak, and causative vessel. Possible reasons
      for poor success rates will also be discussed. A general consensus on how to best
      manage these patients is yet to be reached. The aim of this review is to give an
      overview of type II endoleaks, their natural history and vessels most commonly
      involved, as well as different approaches to embolisation. 

PMID- 24013538
TI  - Juxtarenal aortic aneurysms: preliminary experience with fenestrated E-vita
      abdominal stent-graft.
AB  - Endovascular aneurysm repair (EVAR) offers a minimally invasive treatment to
      patients with improved short-term and similar mid-term results compared to
      conventional, open repair. Approximately 20% of patients have an aneurysm neck
      morphology inadequate for a standard stent-graft and requires an endograft to
      cross vital aortic side branches to achieve a seal. This work describes the
      promising single center preliminary results in the management of juxtarenal
      aortic aneurysm using E-vita stent-graft. 

PMID- 24013539
TI  - Expansion of an iliac aneurysm after treatment with multilayer stent: an unusual
      case.
AB  - A 62 year old man, suffering from arterial hypertension and no other significant
      comorbidities come to our attention for the presence of an asymptomatic 29 mm
      left common iliac artery (CIA) aneurysm and bladder cancer. Given the young age
      of the patient, we opted for endovascular treatment that would allow to maintain
      the patency of the hypogastric artery. In June 2011, the patient underwent an
      endovascular exclusion of the left iliac artery aneurysm corrected by multilayer
      stent placement (Cardiatis 16x120mm) and post-dilatation with 14x40 mm balloon
      (Medtronic Reliant). At the 3 months follow-up, a CT-angio was made, showing a
      Type I endoleak with complete perfusion of the aneurismal sac. We analysed the CT
      Angio using OsiriX and at the 3D reconstruction a poor adhesion of the stent to
      the proximal neck was detected. We decided to intervene by implanting two balloon
      expendable covered stents (Atrium Adventa; 16x40 mm) The aneurysm sac remained
      stable for 9 months but at 12 months follow-up the aneurysm presented a diameter
      of 39mm. Due to the increase of the aneurysm sac, we decided to implant a stent
      graft 16-10x95+10-10x80 mm (Medtronic Endurant) with complete exclusion of the
      aneurysm and internal iliac artery occlusion. At one month follow-up the patient
      is completed asymptomatic with no endoleak at the Duplex scan and at the CT
      Angio. 

PMID- 24013540
TI  - Stent-graft and multilayer stent for treatment of type II thoracoabdominal aortic
      aneurysm in a high-risk patient.
AB  - The aim of the present article was to present an alternative endovascular
      treatment for type II thoracoabdominal aortic aneurysm that would have the
      advantage of limiting the duration of the procedure and the use of contrast. A
      high-risk patient was admitted to our Vascular Unit for type II thoracoabdominal
      aneurysm according to Crawford's classification. Two thoracic stent-grafts
      (Valiant Captivia, Medtronic, Pewaukee, WI, USA), a bifurcated stent-graft
      (Endurant Medtronic) and two multilayer stents (Cardiatis SA, Isnes, Belgium)
      were deployed. No postoperative major complications were observed. Operative time
      and use of contrast material were 45 min and 80 mL, respectively. Computed
      angiography tomography at 1 and 6 months showed patency of visceral and renal
      arteries and progressive thrombosis of the aneurysmal sac. This stent-graft
      treatment in combination with multilayer stent could be an alternative treatment
      for thoracoabdominal aneurysm in high-risk patients. 

PMID- 24013541
TI  - Mammary artery to saphenous vein composite T grafts for coronary artery bypass:
      late follow-up.
AB  - AIM: Composite arterial grafts using a T configuration from the left internal
      mammary artery (LIMA) are commonly used for coronary artery surgery. Little data
      exist regarding the use of saphenous vein (SV) in composite grafts from the LIMA.
      This study aimed to determine whether LIMA patency was reduced by the attachment
      of a SV T graft. METHODS: Patients (N.=166) who underwent coronary bypass surgery
      using the LIMA for SV graft inflow were identified from a database. Post
      discharge angiography was performed for investigation of symptoms or evidence of
      myocardial ischemia. Follow-up identified episodes of angiography, re
      intervention and death. RESULTS: Complete follow-up was obtained in 165 patients,
      mean 6 years (0-16 years). The mean patient age was 70 years and 43 patients
      underwent concomitant procedures. In 25 patients who underwent post discharge
      angiography, the LIMA and T anastomoses were widely patent in 14 patients. The SV
      graft was occluded at the T anastomosis in 8 patients and the distal limb of the
      LIMA was occluded in 2 patients. In no patients were the vein and LIMA both
      occluded. CONCLUSION: The use of the LIMA for SV graft inflow does not appear to
      compromise the LIMA graft even when SV graft occlusion occurs.

PMID- 24013542
TI  - Predictors and outcomes of minor cerebrovascular events after cardiac surgery: a
      multivariable analysis of 1346 patients.
AB  - AIM: There are no extensive data exist regarding the epidemiology and prognosis
      of minor cerebrovascular events (MCVE) in adults after cardiac surgery. The aim
      of this study was to determine perioperative predictors of MCVE and impact on
      postoperative outcomes after cardiac surgery. METHODS: The database of 1346 adult
      patients between June 2004-May 2011 were retrospectively analyzed to determine
      risk factors for postoperative MCVE and prognostic impact in our instution. MCVE
      was defined as ''a new focal neurologic deficit which appears in the
      postoperative period''. Data were collected on patient characteristics,
      intraoperative variables and outcomes, postoperative course, and discharge status
      by univariate analyses. Then multivariate logistic regression with forward
      elimination determined six important denominators of the 24 factors examined on
      univariate analysis for MCVE. RESULTS: Twenty-six patients suffered a
      postoperative minor stroke (2%) at a median of 24 hours postoperatively. Head
      computed tomography was performed in 19 patients (73%) of whom ischemic stroke
      were identified in 4 (21.05%) patients and pituitary macroadenoma was diagnosed
      in one patient treated with surgery. Patients who experienced MCVE had no
      operative mortality and were discharged without any neurological deficit.
      Multivariable logistic regression analysis identified six risk factors for MCVE:
      unstable angina pectoris, hyperlipidemia, cerebrovascular accident within two
      years, EF<50, intra-aortic balloon counterpulsation and higher Euroscore values.
      CONCLUSION: Unstable angina pectoris, hyperlipidemia, cerebrovascular accident
      within last two years, EF<50, intra-aortic balon counterpulsation and higher
      Euroscore values in adults after cardiac surgery are independent predictors of
      minor stroke as compared with similar predictors of major stroke.

PMID- 24013543
TI  - Organized follow-up is essential for the evaluation of cardiac surgery.
AB  - AIM: Follow-up in adult cardiac surgery seems problematic. Mostly only hospital
      data are presented. Evaluation of performed cardiac surgery, is based on these
      data. However is this appropriate? This study evaluates the results of our follow
      up (FU) in terms of completeness, drop out and survival in relation to the
      operative risk and the difference between hospital mortality, 30-day, 6-month and
      1-year mortality. METHODS: Three thousand three hundred twenty-eight patients
      operated between January 2007 and December 2010 were included. Hospital mortality
      was 1.68% (56/3328). The date of mortality or the last date of information is
      endpoint. Our FU is twofold, the Organized FU (OFU) a yearly performed FU by mean
      of a written survey directly to all patients. A non-organized FU (NOFU) covering
      all information supplied spontaneously by cardiologists, general practitionars,
      family or others. RESULTS: Completeness decreases from 99.1% at 30-days over
      85.6% at 1-year postoperative. During the first year there is no statistical
      significant difference between patients in or lost for FU, concerning age and
      Euroscore risk. Survival analysis shows a difference in one-year survival related
      to the risk.The statistical difference between hospital mortality and the
      registered 30-day, 6-month and 1-year mortality is related to the Euroscore risk
      class but also to the number of unobserved patients survival or mortality.
      CONCLUSION: This study shows that hospital mortality, 30-day-, 6 months- and 1
      year mortality is related to the operative risk and the number of unobserved
      patients Most efficient seems an OFU at one year postoperative, where not only
      mortality but also survival is registered.

PMID- 24013544
TI  - A new versatile class of hetero-tetra-metallic assemblies: highlighting single
      molecule magnet behaviour.
AB  - Hetero-tetra-metallic species based on hexanuclear assemblies
      [((valen)M1)Ln(OH2)2(MUM2(CN)8)]2(2-) (Ln = Gd(III), Tb(III); M1 = Cu(II), Ni(II)
      and M2 = Mo(IV), W(IV)) and co-crystallized mononuclear complexes [M3(tpy)2](2+)
      (M3 = Ni(II), Ru(II), Os(II)) were identified, fully characterized, and shown to
      constitute a new class of single-molecule magnets. 

PMID- 24013545
TI  - Why translation counts for mitochondria - retrograde signalling links
      mitochondrial protein synthesis to mitochondrial biogenesis and cell
      proliferation.
AB  - Organelle biosynthesis is a key requirement for cell growth and division. The
      regulation of mitochondrial biosynthesis exhibits additional layers of complexity
      compared with that of other organelles because they contain their own genome and
      dedicated ribosomes. Maintaining these components requires gene expression to be
      coordinated between the nucleo-cytoplasmic compartment and mitochondria in order
      to monitor organelle homeostasis and to integrate the responses to the
      physiological and developmental demands of the cell. Surprisingly, the parameters
      that are used to monitor or count mitochondrial abundance are not known, nor are
      the signalling pathways. Inhibiting the translation on mito-ribosomes genetically
      or with antibiotics can impair cell proliferation and has been attributed to
      defects in aerobic energy metabolism, even though proliferating cells rely
      primarily on glycolysis to fuel their metabolic demands. However, a recent study
      indicates that mitochondrial translational stress and the rescue mechanisms that
      relieve this stress cause the defect in cell proliferation and occur before any
      impairment of oxidative phosphorylation. Therefore, the process of mitochondrial
      translation in itself appears to be an important checkpoint for the monitoring of
      mitochondrial homeostasis and might have a role in establishing mitochondrial
      abundance within a cell. This hypothesis article will explore the evidence
      supporting a role for mito-ribosomes and translation in a mitochondria-counting
      mechanism. 

PMID- 24013546
TI  - The sirtuin SIRT6 regulates stress granule formation in C. elegans and mammals.
AB  - SIRT6 is a NAD(+)-dependent deacetylase that modulates chromatin structure and
      safeguards genomic stability. Until now, SIRT6 has been assigned to the nucleus
      and only nuclear targets of SIRT6 are known. Here, we demonstrate that in
      response to stress, C. elegans SIR-2.4 and its mammalian orthologue SIRT6
      localize to cytoplasmic stress granules, interact with various stress granule
      components and induce their assembly. Loss of SIRT6 or inhibition of its
      catalytic activity in mouse embryonic fibroblasts impairs stress granule
      formation and delays disassembly during recovery, whereas deficiency of SIR-2.4
      diminishes maintenance of P granules and decreases survival of C. elegans under
      stress conditions. Our findings uncover a novel, evolutionary conserved function
      of SIRT6 in the maintenance of stress granules in response to stress. 

PMID- 24013547
TI  - Dynamic association of the ULK1 complex with omegasomes during autophagy
      induction.
AB  - Induction of autophagy requires the ULK1 protein kinase complex and the Vps34
      lipid kinase complex. PtdIns3P synthesised by Vps34 accumulates in omegasomes,
      membrane extensions of the ER within which some autophagosomes form. The ULK1
      complex is thought to target autophagosomes independently of PtdIns3P, and its
      functional relationship to omegasomes is unclear. Here we show that the ULK1
      complex colocalises with omegasomes in a PtdIns3P-dependent way. Live-cell
      imaging of Atg13 (a ULK1 complex component), omegasomes and LC3 establishes and
      annotates for the first time a complete sequence of steps leading to
      autophagosome formation, as follows. Upon starvation, the ULK1 complex forms
      puncta associated with the ER and sporadically with mitochondria. If PtdIns3P is
      available, these puncta become omegasomes. Subsequently, the ULK1 complex exits
      omegasomes and autophagosomes bud off. If PtdIns3P is unavailable, ULK1 puncta
      are greatly reduced in number and duration. Atg13 contains a region with affinity
      for acidic phospholipids, required for translocation to punctate structures and
      autophagy progression.

PMID- 24013549
TI  - Nucleophagy at a glance.
AB  - Under certain circumstances, the removal of damaged or non-essential parts of the
      nucleus, or even an entire nucleus, is crucial in order to promote cell longevity
      and enable proper function. A selective form of autophagy, known as nucleophagy,
      can be used to accomplish the degradation of nucleus-derived material. In this
      Cell Science at a Glance article and the accompanying poster, we summarize the
      similarities and differences between the divergent modes of nucleophagy that have
      been described to date, emphasizing, where possible, the molecular mechanism, the
      membrane interactions and rearrangements, and the nature of the nucleus-derived
      material that is degraded. In turn, we will consider nucleophagy processes in the
      lower eukaryotes, the budding yeast Saccharomyces cerevisiae, filamentous fungi
      Aspergillus and Magnaporthe oryzae and the ciliated protozoan Tetrahymena
      thermophila, and finally in mammalian cells. We will also briefly discuss the
      emerging links between nucleophagy and human disease.

PMID- 24013548
TI  - Activation of the Ca2+-sensing receptor induces deposition of tight junction
      components to the epithelial cell plasma membrane.
AB  - The Ca(2+)-sensing receptor (CaSR) belongs to the G-protein-coupled receptor
      superfamily and plays essential roles in divalent ion homeostasis and cell
      differentiation. Because extracellular Ca(2+) is essential for the development of
      stable epithelial tight junctions (TJs), we hypothesized that the CaSR
      participates in regulating TJ assembly. We first assessed the expression of the
      CaSR in Madin-Darby canine kidney (MDCK) cells at steady state and following
      manipulations that modulate TJ assembly. Next, we examined the effects of CaSR
      agonists and antagonists on TJ assembly. Immunofluorescence studies indicate that
      endogenous CaSR is located at the basolateral pole of MDCK cells. Stable
      transfection of human CaSR in MDCK cells further reveals that this protein co
      distributes with beta-catenin on the basolateral membrane. Switching MDCK cells
      from low-Ca(2+) medium to medium containing a normal Ca(2+) concentration
      significantly increases CaSR expression at both the mRNA and protein levels.
      Exposure of MDCK cells maintained in low-Ca(2+) conditions to the CaSR agonists
      neomycin, Gd(3+) or R-568 causes the transient relocation of the tight junction
      components ZO-1 and occludin to sites of cell-cell contact, while inducing no
      significant changes in the expression of mRNAs encoding junction-associated
      proteins. Stimulation of CaSR also increases the interaction between ZO-1 and the
      F-actin-binding protein I-afadin. This effect does not involve activation of the
      AMP-activated protein kinase. By contrast, CaSR inhibition by NPS-2143
      significantly decreases interaction of ZO-1 with I-afadin and reduces deposition
      of ZO-1 at the cell surface following a Ca(2+) switch from 5 uM to 200 uM
      [Ca(2+)]e. Pre-exposure of MDCK cells to the cell-permeant Ca(2+) chelator BAPTA
      AM, similarly prevents TJ assembly caused by CaSR activation. Finally, stable
      transfection of MDCK cells with a cDNA encoding a human disease-associated gain
      of-function mutant form of the CaSR increases the transepithelial electrical
      resistance of these cells in comparison to expression of the wild-type human
      CaSR. These observations suggest that the CaSR participates in regulating TJ
      assembly. 

PMID- 24013551
TI  - LPS induces mediators of neuroinflammation, cell proliferation, and GFAP
      expression in human astrocytoma cells U373MG: the anti-inflammatory and anti
      proliferative effect of guggulipid.
AB  - Neuroinflammation has been considered to be an integrated part of human
      neurodegenerative diseases. In this study, we examined the effect of guggulipid
      on cell proliferation, nitrite release, interleukin IL-6 and IL-1 beta release,
      and expression of COX-2 and glial fibrillary acidic protein (GFAP) in LPS
      stimulated U373MG cells. LPS significantly stimulated human astrocytoma cells
      U373MG by up-regulating these neuroinflammatory mediators. Guggulipid alone had
      no effect on the cell proliferation of U373MG cells. The up regulation in nitrite
      release, cell proliferation, and release of IL-6 and IL-1 beta in LPS stimulated
      human astrocytoma cells were dose-dependently inhibited by co-treatment with
      guggulipid. The expression level of COX-2 and GFAP proteins was up regulated by
      LPS but the increased level of COX-2 and GFAP was significantly down regulated by
      treatment with guggulipid. These data indicate that guggulipid has a modulatory
      effect on all these parameters, which might explain its beneficial effect in the
      treatment of neuroinflammation-associated disorders directly relating to human
      aspects.

PMID- 24013552
TI  - Primary central nervous system lymphoma mimicking Bickerstaff's encephalitis.

PMID- 24013550
TI  - DNA methylation profiling in human B cells reveals immune regulatory elements and
      epigenetic plasticity at Alu elements during B-cell activation.
AB  - Memory is a hallmark of adaptive immunity, wherein lymphocytes mount a superior
      response to a previously encountered antigen. It has been speculated that
      epigenetic alterations in memory lymphocytes contribute to their functional
      distinction from their naive counterparts. However, the nature and extent of
      epigenetic alterations in memory compartments remain poorly characterized. Here
      we profile the DNA methylome and the transcriptome of B-lymphocyte subsets
      representing stages of the humoral immune response before and after antigen
      exposure in vivo from multiple humans. A significant percentage of activation
      induced losses of DNA methylation mapped to transcription factor binding sites.
      An additional class of demethylated loci mapped to Alu elements across the genome
      and accompanied repression of DNA methyltransferase 3A. The activation-dependent
      DNA methylation changes were largely retained in the progeny of activated B
      cells, generating a similar epigenetic signature in downstream memory B cells and
      plasma cells with distinct transcriptional programs. These findings provide
      insights into the methylation dynamics of the genome during cellular
      differentiation in an immune response. 

PMID- 24013553
TI  - Primary care quality and safety systems in the English National Health Service: a
      case study of a new type of primary care provider.
AB  - OBJECTIVES: Although the predominant model of general practice in the UK National
      Health Service (NHS) remains the small partnership owned and run by general
      practitioners (GPs), new types of provider are emerging. We sought to
      characterize the quality and safety systems and processes used in one large,
      privately owned company providing primary care through a chain of over 50 general
      practices in England. METHODS: Senior staff with responsibility for policy on
      quality and safety were interviewed. We also undertook ethnographic observation
      in non-clinical areas and interviews with staff in three practices. RESULTS: A
      small senior executive team set policy and strategy on quality and safety,
      including a systematic incident reporting and investigation system and processes
      for disseminating learning with a strong emphasis on customer focus.
      Standardization of systems was possible because of the large number of practices.
      Policies appeared generally well implemented at practice level. However, there
      was some evidence of high staff turnover, particularly of GPs. This caused
      problems for continuity of care and challenges in inducting new GPs in the
      company's systems and procedures. CONCLUSIONS: A model of primary care delivery
      based on a corporate chain may be useful in standardizing policies and
      procedures, facilitating implementation of systems, and relieving clinical staff
      of administrative duties. However, the model also poses some risks, including
      those relating to stability. Provider forms that retain the long term, personal
      commitment of staff to their practices, such as federations or networks, should
      also be investigated; they may offer the benefits of a corporate chain combined
      with the greater continuity and stability of the more traditional general
      practice.

PMID- 24013554
TI  - Impact of two different health systems on the burden of type 2 diabetes.
AB  - OBJECTIVES: Health policy directs the management of patients with chronic disease
      in a country, but evaluating nationwide policies is difficult, not least because
      of the absence of suitable comparators. This paper examines the management of
      patients with type 2 diabetes in two demographically comparable populations with
      different health care systems to see if this represents a viable approach to
      evaluation. METHODS: A secondary analysis of centralized prescribing databases
      for 2010 was undertaken to compare the levels and costs of care of patients with
      type 2 diabetes in Northern Ireland's National Health Service (NHS) (NI, n = 1.8
      million) which has structured care, financial incentives related to diabetes care
      and an emphasis on generic prescribing, with that of the Republic of Ireland
      (ROI, n = 4.3 million) where management of diabetes care is guided solely by
      clinical and other guidelines. RESULTS: The prevalence of treated type 2 diabetes
      was 3.59% in NI and 3.09% in ROI, but there were similar and high levels of
      prescribing of secondary cardiovascular medications. Medication costs per person
      for anti-diabetic, anti-obesity and cardiovascular medication were 46% higher in
      ROI than NI, due to differences in levels of generic prescribing. CONCLUSIONS:
      These different health care systems appear to be producing similar levels of care
      for patients with type 2 diabetes, although at different levels of cost. The
      findings question the need for financial incentives in NI and highlight the large
      cost savings potentially accruing from a greater shift to generic prescribing in
      ROI. Cross-country comparison, though not without difficulties, may prove a
      useful adjunct to within-country analysis of policy impact.

PMID- 24013555
TI  - Workplace stress in community pharmacies in England: associations with
      individual, organizational and job characteristics.
AB  - OBJECTIVES: To describe the levels of workplace stress that community pharmacists
      perceive and to examine associations with individual, organizational and job
      characteristics. METHODS: A cross-sectional mailed survey of 2000 randomly
      selected community pharmacists practising in England incorporating a validated
      organizational stress screening tool (ASSET). RESULTS: Response rate was 48%.
      Community pharmacists reported significantly higher levels of stress than other
      health care workers for seven out of eight work-related stressors. Regression
      analyses demonstrated significant associations between a number of individual,
      organizational and job characteristics and stress. Long working days, being a
      pharmacy manager and working for large multiples were associated with higher
      reported levels of stress across a number of work-related stressors including
      work overload, control and the job itself. However, self-reported measures of
      workload (such as dispensing volume) were not associated with higher stress
      levels. CONCLUSIONS: The growth in corporate ownership of community pharmacies,
      which is associated with more stressful working environments, together with
      current economic pressures could have consequences not only for the future well
      being of pharmacists but also for patient safety.

PMID- 24013556
TI  - Bit-by-bit autophagic removal of parkin-labelled mitochondria.
AB  - Eukaryotic cells maintain mitochondrial integrity through mitophagy, an
      autophagic process by which dysfunctional mitochondria are selectively
      sequestered into double-layered membrane structures, termed phagophores, and
      delivered to lysosomes for degradation. Here we show that small fragments of
      parkin-labelled mitochondria at omegasome-marked sites are engulfed by autophagic
      membranes one at a time. Using a light-activation scheme to impair long
      mitochondrial tubules, we demonstrate that sites undergoing bit-by-bit mitophagy
      display preferential ubiquitination, and are situated where parkin-labelled
      mitochondrial tubules and endoplasmic reticulum intersect. Our observations
      suggest contact regions between the endoplasmic reticulum and impaired
      mitochondria are initiation sites for local LC3 recruitment and mitochondrial
      remodelling that support bit-by-bit, parkin-mediated mitophagy. These results
      help in understanding how cells manage to fit large and morphologically
      heterogeneous mitochondria into micron-sized autophagic membranes during
      mitophagy. 

PMID- 24013557
TI  - Chemical, mineralogical and morphological changes in weathered coal fly ash: a
      case study of a brine impacted wet ash dump.
AB  - The mobility of species in coal fly ash (FA), co-disposed with brine using a wet
      ash handling system, from a coal fired power generating utility has been
      investigated. The study was conducted in order to establish if the wet ash dump
      could act as a salt sink. The ash was dumped as a slurry with 5:1 brine/ash ratio
      and the dam was in operation for 20 years. Weathered FA samples were collected
      along three cores at a South African power station's wet ash dump by drilling and
      sampling the ash at 1.5 m depth intervals. A fresh FA sample was collected from
      the hoppers in the ash collection system at the power station. Characterization
      of both fresh FA and weathered FA obtained from the drilled cores S1, S2 and S3
      was done using X-ray diffraction (XRD) for mineralogy, X-ray fluorescence (XRF)
      for chemical composition and scanning electron microscopy (SEM) for morphology.
      Analysis of extracted pore water and moisture content determination of the fresh
      FA and the weathered FA obtained from the drilled cores S1, S2 and S3 was done in
      order to evaluate the physico-chemical properties of the FA. The XRD analysis
      revealed changes in mineralogy along cores S1, S2 and S3 in comparison with the
      fresh FA. The SEM analysis revealed spherical particles with smooth outer
      surfaces for the fresh FA while the weathered ash samples obtained from cores S1,
      S2 and S3 consisted of agglomerated, irregular particles appearing to be
      encrusted, etched and corroded showing that weathering and leaching had occurred
      in the ash dump. The moisture content (MC) analysis carried out on the fresh FA
      (1.8%) and the weathered FA obtained from the drilled cores S1 (41.4-73.2%), S2
      (30.3-94%) and S3 (21.7-76.2%)indicated that the ash dump was water logged hence
      creating favourable conditions for leaching of species. The fresh fly ash (n = 3)
      had a pH of 12.38 +/- 0.15, EC value of 4.98 +/- 0.03 mS/cm and TDS value of 2.68
      +/- 0.03 g/L, the pH of the drilled core S1 (n = 45) was 10.04 +/- 0.50, the EC
      value was 1.08 +/- 0.14 mS/cm and the TDS value was 0.64 +/- 0.08 g/L. Core S2 (n
      = 105) had pH of 10.04 +/- 0.23; EC was 1.08 +/- 0.06 mS/cm and TDS was 0.64 +/-
      0.04 g/L, while core S3 (n = 66) had pH of 11.04 +/- 0.09; EC was 0.99 +/- 0.03
      mS/cm and TDS was 0.57 +/- 0.01 g/L. The changes in pH values can be attributed
      to the dissolution and flushing out of alkaline oxides like CaO and MgO from the
      dumped ash. The variations in pH values shows that the fly ash is acidifying over
      time and metal mobility can be expected under these conditions. The large
      decrease of EC in the drilled ash cores S1, S2 and S3 compared to the fresh ash
      indicated a major loss of ionic species over time in the ash dump. The XRF
      analysis showed the progressive dissolution of the major aluminosilicate ash
      matrix which influenced the release of minor and trace elements into the pore
      water enhancing their mobility as the ash dam acidified over time. Brine co
      disposal on the ash may have been responsible for the slight enrichment of some
      species such as Na (0.27-0.56%), SO4(2-) (0.06-0.08%), Mg (0.57-0.96 %) and K
      (0.02-0.34%) in the disposed weathered FA. However, there was no significant
      accumulation of these species in the disposed FA despite continuous addition of
      large volumes of highly saline brine over the 20 year period that the dump
      existed, indicating that the ash dam was incapable of holding salts and
      continually released elements to the environment over the lifetime of the dam. 

PMID- 24013558
TI  - Prospective and participatory integrated assessment of agricultural systems from
      farm to regional scales: Comparison of three modeling approaches.
AB  - Evaluating the impacts of the development of alternative agricultural systems,
      such as organic or low-input cropping systems, in the context of an agricultural
      region requires the use of specific tools and methodologies. They should allow a
      prospective (using scenarios), multi-scale (taking into account the field, farm
      and regional level), integrated (notably multicriteria) and participatory
      assessment, abbreviated PIAAS (for Participatory Integrated Assessment of
      Agricultural System). In this paper, we compare the possible contribution to
      PIAAS of three modeling approaches i.e. Bio-Economic Modeling (BEM), Agent-Based
      Modeling (ABM) and statistical Land-Use/Land Cover Change (LUCC) models. After a
      presentation of each approach, we analyze their advantages and drawbacks, and
      identify their possible complementarities for PIAAS. Statistical LUCC modeling is
      a suitable approach for multi-scale analysis of past changes and can be used to
      start discussion about the futures with stakeholders. BEM and ABM approaches have
      complementary features for scenarios assessment at different scales. While ABM
      has been widely used for participatory assessment, BEM has been rarely used
      satisfactorily in a participatory manner. On the basis of these results, we
      propose to combine these three approaches in a framework targeted to PIAAS. 

PMID- 24013559
TI  - Can we build better compost? Use of waste drywall to enhance plant growth on
      reclamation sites.
AB  - Compost is a readily available source of organic matter and nutrients and is
      produced large scale in many jurisdictions. Novel advancements in composting
      include addition of construction waste, such as drywall, to address its disposal
      while potentially improving compost quality for use in land reclamation. Varying
      compositions (15-30% by weight) of coarse and ground waste drywall were added to
      manure and biosolids during composting. Six composts were applied at four rates
      (0, 50, 100, 200 Mg ha(-1)) to three reclamation soils (agricultural, urban clean
      fill, oil sands tailings). Response to composts was assessed in the greenhouse
      with three plant species (Hordeum vulgare L. (barley), Agropyron trachycaulum
      (Link) Malte (slender wheat grass) and Festuca saximontana Rydb. (rocky mountain
      fescue). Drywall added to biosolids or manure during composting had no
      detrimental effects on vegetation; any negative effects of compost occurred with
      and without drywall. In agricultural soil and clean fill, biosolids composts with
      15% coarse and 18% ground drywall improved native grass response, particularly
      biomass, relative to biosolids compost without drywall. Drywall manure composts
      reduced native grass response relative to manure compost without drywall. Only
      low quality tailings sand was improved by 30% coarse drywall. Compost rate
      significantly affected above and below ground biomass in agricultural soil and
      reduced performance of native species at highest rates, suggesting a threshold
      beyond which conditions will not be suitable for reclamation. Grinding drywall
      did not significantly improve plant performance and use of coarse drywall would
      eliminate the need for specialized equipment and resources. This initial research
      demonstrates that drywall composts are appropriate soil amendments for
      establishment of native and non native plant species on reclamation sites with
      consideration of substrate properties and plant species tolerances to dictate
      which additional feed stocks should be used. 

PMID- 24013560
TI  - Mechanical properties of DNA-like polymers.
AB  - The molecular structure of the DNA double helix has been known for 60 years, but
      we remain surprisingly ignorant of the balance of forces that determine its
      mechanical properties. The DNA double helix is among the stiffest of all
      biopolymers, but neither theory nor experiment has provided a coherent
      understanding of the relative roles of attractive base stacking forces and
      repulsive electrostatic forces creating this stiffness. To gain insight, we have
      created a family of double-helical DNA-like polymers where one of the four normal
      bases is replaced with various cationic, anionic or neutral analogs. We apply DNA
      ligase-catalyzed cyclization kinetics experiments to measure the bending and
      twisting flexibilities of these polymers under low salt conditions.
      Interestingly, we show that these modifications alter DNA bending stiffness by
      only 20%, but have much stronger (5-fold) effects on twist flexibility. We
      suggest that rather than modifying DNA stiffness through a mechanism easily
      interpretable as electrostatic, the more dominant effect of neutral and charged
      base modifications is their ability to drive transitions to helical conformations
      different from canonical B-form DNA. 

PMID- 24013561
TI  - Co-operation of BRCA1 and POH1 relieves the barriers posed by 53BP1 and RAP80 to
      resection.
AB  - In G2 phase cells, DNA double-strand break repair switches from DNA non
      homologous end-joining to homologous recombination. This switch demands the
      promotion of resection. We examine the changes in 53BP1 and RAP80 ionizing
      radiation induced foci (IRIF) in G2 phase, as these are factors that restrict
      resection. We observed a 2-fold increase in the volume of 53BP1 foci by 8 h,
      which is not seen in G1 cells. Additionally, an IRIF core devoid of 53BP1 arises
      where RPA foci form, with BRCA1 IRIF forming between 53BP1 and replication
      protein A (RPA). Ubiquitin chains assessed using alpha-FK2 antibodies are
      similarly repositioned. Repositioning of all these components requires BRCA1's
      BRCT but not the ring finger domain. 53BP1, RAP80 and ubiquitin chains are
      enlarged following POH1 depletion by small interfering RNA, but a devoid core
      does not form and RPA foci formation is impaired. Co-depletion of POH1 and RAP80,
      BRCC36 or ABRAXAS allows establishment of the 53BP1 and ubiquitin chain-devoid
      core. Thus, the barriers posed by 53BP1 and RAP80 are relieved by BRCA1 and POH1,
      respectively. Analysis of combined depletions shows that these represent distinct
      but interfacing barriers to promote loss of ubiquitin chains in the IRIF core,
      which is required for subsequent resection. We propose a model whereby BRCA1
      impacts on 53BP1 to allow access of POH1 to RAP80. POH1-dependent removal of
      RAP80 within the IRIF core enables degradation of ubiquitin chains, which
      promotes loss of 53BP1. Thus, POH1 represents a novel component regulating the
      switch from non-homologous end-joining to homologous recombination. 

PMID- 24013562
TI  - Efficient genome editing in Caenorhabditis elegans by CRISPR-targeted homologous
      recombination.
AB  - Cas9 is an RNA-guided double-stranded DNA nuclease that participates in clustered
      regularly interspaced short palindromic repeats (CRISPR)-mediated adaptive
      immunity in prokaryotes. CRISPR-Cas9 has recently been used to generate insertion
      and deletion mutations in Caenorhabditis elegans, but not to create tailored
      changes (knock-ins). We show that the CRISPR-CRISPR-associated (Cas) system can
      be adapted for efficient and precise editing of the C. elegans genome. The
      targeted double-strand breaks generated by CRISPR are substrates for transgene
      instructed gene conversion. This allows customized changes in the C. elegans
      genome by homologous recombination: sequences contained in the repair template
      (the transgene) are copied by gene conversion into the genome. The possibility to
      edit the C. elegans genome at selected locations will facilitate the systematic
      study of gene function in this widely used model organism. 

PMID- 24013564
TI  - Use of extremely short Forster resonance energy transfer probes in real-time
      polymerase chain reaction.
AB  - Described in the article is a new approach for the sequence-specific detection of
      nucleic acids in real-time polymerase chain reaction (PCR) using fluorescently
      labeled oligonucleotide probes. The method is based on the production of PCR
      amplicons, which fold into dumbbell-like secondary structures carrying a
      specially designed 'probe-luring' sequence at their 5' ends. Hybridization of
      this sequence to a complementary 'anchoring' tail introduced at the 3' end of a
      fluorescent probe enables the probe to bind to its target during PCR, and the
      subsequent probe cleavage results in the florescence signal. As it has been shown
      in the study, this amplicon-endorsed and guided formation of the probe-target
      duplex allows the use of extremely short oligonucleotide probes, up to
      tetranucleotides in length. In particular, the short length of the fluorescent
      probes makes possible the development of a 'universal' probe inventory that is
      relatively small in size but represents all possible sequence variations. The
      unparalleled cost-effectiveness of the inventory approach is discussed. Despite
      the short length of the probes, this new method, named Angler real-time PCR,
      remains highly sequence specific, and the results of the study indicate that it
      can be effectively used for quantitative PCR and the detection of polymorphic
      variations. 

PMID- 24013563
TI  - Suppression of HPV-16 late L1 5'-splice site SD3632 by binding of hnRNP D
      proteins and hnRNP A2/B1 to upstream AUAGUA RNA motifs.
AB  - Human papillomavirus type 16 (HPV-16) 5'-splice site SD3632 is used exclusively
      to produce late L1 mRNAs. We identified a 34-nt splicing inhibitory element
      located immediately upstream of HPV-16 late 5'-splice site SD3632. Two AUAGUA
      motifs located in these 34 nt inhibited SD3632. Two nucleotide substitutions in
      each of the HPV-16 specific AUAGUA motifs alleviated splicing inhibition and
      induced late L1 mRNA production from episomal forms of the HPV-16 genome in
      primary human keratinocytes. The AUAGUA motifs bind specifically not only to the
      heterogeneous nuclear RNP (hnRNP) D family of RNA-binding proteins including
      hnRNP D/AUF, hnRNP DL and hnRNP AB but also to hnRNP A2/B1. Knock-down of these
      proteins induced HPV-16 late L1 mRNA expression, and overexpression of hnRNP
      A2/B1, hnRNP AB, hnRNP DL and the two hnRNP D isoforms hnRNP D37 and hnRNP D40
      further suppressed L1 mRNA expression. This inhibition may allow HPV-16 to hide
      from the immune system and establish long-term persistent infections with
      enhanced risk at progressing to cancer. There is an inverse correlation between
      expression of hnRNP D proteins and hnRNP A2/B1 and HPV-16 L1 production in the
      cervical epithelium, as well as in cervical cancer, supporting the conclusion
      that hnRNP D proteins and A2/B1 inhibit HPV-16 L1 mRNA production. 

PMID- 24013565
TI  - RILES, a novel method for temporal analysis of the in vivo regulation of miRNA
      expression.
AB  - Novel methods are required to investigate the complexity of microRNA (miRNA)
      biology and particularly their dynamic regulation under physiopathological
      conditions. Herein, a novel plasmid-based RNAi-Inducible Luciferase Expression
      System (RILES) was engineered to monitor the activity of endogenous RNAi
      machinery. When RILES is transfected in a target cell, the miRNA of interest
      suppresses the expression of a transcriptional repressor and consequently switch
      ON the expression of the luciferase reporter gene. Hence, miRNA expression in
      cells is signed by the emission of bioluminescence signals that can be monitored
      using standard bioluminescence equipment. We validated this approach by
      monitoring in mice the expression of myomiRs-133, -206 and -1 in skeletal muscles
      and miRNA-122 in liver. Bioluminescence experiments demonstrated robust
      qualitative and quantitative data that correlate with the miRNA expression
      pattern detected by quantitative RT-PCR (qPCR). We further demonstrated that the
      regulation of miRNA-206 expression during the development of muscular atrophy is
      individual-dependent, time-regulated and more complex than the information
      generated by qPCR. As RILES is simple and versatile, we believe that this
      methodology will contribute to a better understanding of miRNA biology and could
      serve as a rationale for the development of a novel generation of regulatable
      gene expression systems with potential therapeutic applications. 

PMID- 24013566
TI  - Structural insights of non-canonical U*U pair and Hoogsteen interaction probed
      with Se atom.
AB  - Unlike DNA, in addition to the 2'-OH group, uracil nucleobase and its
      modifications play essential roles in structure and function diversities of non
      coding RNAs. Non-canonical U*U base pair is ubiquitous in non-coding RNAs, which
      are highly diversified. However, it is not completely clear how uracil plays the
      diversifing roles. To investigate and compare the uracil in U-A and U*U base
      pairs, we have decided to probe them with a selenium atom by synthesizing the
      novel 4-Se-uridine ((Se)U) phosphoramidite and Se-nucleobase-modified RNAs ((Se)U
      RNAs), where the exo-4-oxygen of uracil is replaced by selenium. Our crystal
      structure studies of U-A and U*U pairs reveal that the native and Se-derivatized
      structures are virtually identical, and both U-A and U*U pairs can accommodate
      large Se atoms. Our thermostability and crystal structure studies indicate that
      the weakened H-bonding in U-A pair may be compensated by the base stacking, and
      that the stacking of the trans-Hoogsteen U*U pairs may stabilize RNA duplex and
      its junction. Our result confirms that the hydrogen bond (O4(...)H-C5) of the
      Hoogsteen pair is weak. Using the Se atom probe, our Se-functionalization studies
      reveal more insights into the U*U interaction and U-participation in structure
      and function diversification of nucleic acids. 

PMID- 24013567
TI  - Reversed-phase ion-pair liquid chromatography method for purification of duplex
      DNA with single base pair resolution.
AB  - Obtaining quantities of highly pure duplex DNA is a bottleneck in the biophysical
      analysis of protein-DNA complexes. In traditional DNA purification methods, the
      individual cognate DNA strands are purified separately before annealing to form
      DNA duplexes. This approach works well for palindromic sequences, in which top
      and bottom strands are identical and duplex formation is typically complete.
      However, in cases where the DNA is non-palindromic, excess of single-stranded DNA
      must be removed through additional purification steps to prevent it from
      interfering in further experiments. Here we describe and apply a novel reversed
      phase ion-pair liquid chromatography purification method for double-stranded DNA
      ranging in lengths from 17 to 51 bp. Both palindromic and non-palindromic DNA can
      be readily purified. This method has the unique ability to separate blunt double
      stranded DNA from pre-attenuated (n-1, n-2, etc) synthesis products, and from DNA
      duplexes with single base pair overhangs. Additionally, palindromic DNA sequences
      with only minor differences in the central spacer sequence of the DNA can be
      separated, and the purified DNA is suitable for co-crystallization of protein-DNA
      complexes. Thus, double-stranded ion-pair liquid chromatography is a useful
      approach for duplex DNA purification for many applications. 

PMID- 24013568
TI  - Patient satisfaction with service quality as a predictor of survival outcomes in
      breast cancer.
AB  - PURPOSE: Despite the recognized relevance of symptom burden in breast cancer,
      there has been limited exploration of whether an individual patient's assessment
      of the overall quality of care received might influence outcome. We therefore
      evaluated the relationship between patient-reported satisfaction with service
      quality and survival in breast cancer. METHODS: A random sample of 1,521 breast
      cancer patients treated at Cancer Treatment Centers of America. A questionnaire
      which covered several dimensions of patient satisfaction was administered. Items
      were measured on a seven-point Likert scale ranging from "completely
      dissatisfied" to "completely satisfied". Univariate and multivariate Cox
      regression was used to evaluate the association between patient satisfaction and
      survival. RESULTS: Of 1,521 patients, 836 were newly diagnosed, and 685 had
      previously been treated. A number of 409, 611, 323, and 178 patients had stage I,
      II, III, and IV disease, respectively. A total of 1,106 (72.7 %) patients were
      completely satisfied with the overall service quality, while 415 (27.3 %) were
      not. On univariate analysis, completely satisfied patients had a significantly
      lower risk of mortality compared to those not completely satisfied (HR = 0.62; 95
      % CI 0.50-0.76; p < 0.001). On multivariate analysis, completely satisfied
      patients demonstrated significantly lower mortality (HR = 0.71; 95 % CI 0.57
      0.87; p = 0.001) compared to those not completely satisfied. CONCLUSIONS: Patient
      satisfaction with service quality was an independent predictor of survival in
      breast cancer. Further exploration of a possible meaningful relationship between
      patient satisfaction with the care they receive and outcomes in breast cancer is
      indicated.

PMID- 24013569
TI  - Prescription and adherence to lymphedema self-care modalities among women with
      breast cancer-related lymphedema.
AB  - PURPOSE: To profile the prescription for and adherence to breast cancer-related
      lymphedema (BCRL) self-care modalities among breast cancer (BrCa) survivors with
      BCRL in a 12-month randomized weightlifting trial. METHODS: We developed a
      questionnaire that assessed prescription for and adherence to 10 BCRL self-care
      modalities that included physical therapy exercise, pneumatic compression pump,
      medication, lymphedema bandaging, arm elevation, self-administered lymphatic
      drainage, therapist-administered lymphatic drainage, compression garments, skin
      care, and taping. We measured prescription for and adherence to BCRL self-care
      modalities at baseline, 3, 6, and 12 months. Longitudinal logistic regression was
      used to estimate the odds ratio (OR) and 95 % confidence interval (95 % CI)
      associated with prescription for and adherence to BCRL modalities over time.
      RESULTS: This study included 141 BrCa survivors with BCRL. Women were prescribed
      an average of 3.6 +/- 2.1 BCRL self-care modalities during the study. The
      prescription for therapist-administered lymphatic drainage (OR = 0.92, 95 % CI
      0.88-0.96), pneumatic compression pump use (OR = 0.94, 95 % CI 0.89-0.98), and
      bandaging (OR = 0.96, 95 % CI 0.93-0.99) decreased over 12 months of follow-up.
      No other prescribed BCRL self-care modalities changed during the study. Over 12
      months, the average adherence to all BCRL self-care modalities varied with 13,
      24, 32, and 31 % of women reporting <25, 25-49, 50-74, and >=75 % adherence,
      respectively. Over 12 months, there was a noticeable change from high to low
      adherence in self-administered lymphatic drainage, such that there was a 15 %
      increased likelihood of adherence <25 % compared to >=75 % (OR = 1.15 (95 % CI
      1.05-1.26); p = 0.002). The adherence patterns of all other modalities did not
      change over follow-up. CONCLUSIONS: Our findings suggest the prescription for
      BCRL self-care modalities is variable. The average adherence to BCRL self-care
      was non-optimal. Future research is necessary to prepare BrCa survivors with the
      knowledge, skills, abilities, and resources necessary to care for this lifelong
      condition.

PMID- 24013570
TI  - Development and validation of a prognostic scale for hospitalized patients with
      terminally ill cancer in China.
AB  - PURPOSE: The purpose of this study is to develop and validate a scale prognostic
      of survival in hospitalized, terminally ill cancer patients in China. METHODS:
      Terminally ill cancer patients hospitalized at two general hospitals in China
      were prospectively analyzed. Patients were divided into a training cohort (n =
      181) and a testing cohort (n = 128). Factors prognostic of survival were
      identified in the training cohort and combined into a scale, which was validated
      in the testing cohort. RESULTS: In the training cohort, eight factors associated
      with reduced survival were identified: low performance status, dyspnea at rest,
      reduced oral intake, cognitive impairment, edema, leukocytosis, and elevated urea
      and alanine transaminase concentrations. A prognostic prediction score was
      calculated for each patient, based on the weight of these eight predictors in the
      regression model, with scores ranging from 0 (no altered variables) to 12
      (maximal altered variables). Patients with different prognostic scores had
      significantly different prognoses (p < 0.001). A cutoff point of >=4 was optimal
      in categorizing patients with "low" (score <4) and "high" (score >=4) risk of
      survival for less than 30 days, with median survival time in these groups of 47
      and 9 days, respectively. Using this cutoff point on the testing cohort, median
      survival time for the low and high risk groups were 66 and 11 days, respectively.
      CONCLUSION: We identified eight indicators predictive of poor survival in Chinese
      patients hospitalized with terminal cancer. A prognostic scale that includes
      these indicators may help in making decisions about end-of-life care.

PMID- 24013571
TI  - Exome sequencing reveals novel rare variants in the ryanodine receptor and
      calcium channel genes in malignant hyperthermia families.
AB  - BACKGROUND: About half of malignant hyperthermia (MH) cases are associated with
      skeletal muscle ryanodine receptor 1 (RYR1) and calcium channel, voltage
      dependent, L type, alpha1S subunit (CACNA1S) gene mutations, leaving many with an
      unknown cause. The authors chose to apply a sequencing approach to uncover causal
      variants in unknown cases. Sequencing the exome, the protein-coding region of the
      genome, has power at low sample sizes and identified the cause of over a dozen
      Mendelian disorders. METHODS: The authors considered four families with multiple
      MH cases lacking mutations in RYR1 and CACNA1S by Sanger sequencing of
      complementary DNA. Exome sequencing in two affecteds per family, chosen for
      maximum genetic distance, were compared. Variants were ranked by allele
      frequency, protein change, and measures of conservation among mammals to assess
      likelihood of causation. Finally, putative pathogenic mutations were genotyped in
      other family members to verify cosegregation with MH. RESULTS: Exome sequencing
      revealed one rare RYR1 nonsynonymous variant in each of three families
      (Asp1056His, Val2627Met, Val4234Leu), and one CACNA1S variant (Thr1009Lys) in the
      fourth family. These were not seen in variant databases or in our control
      population sample of 5,379 exomes. Follow-up sequencing in other family members
      verified cosegregation of alleles with MH. CONCLUSIONS: The authors found that
      using both exome sequencing and allele frequency data from large sequencing
      efforts may aid genetic diagnosis of MH. In a sample selected by the authors,
      this technique was more sensitive for variant detection in known genes than
      Sanger sequencing of complementary DNA, and allows for the possibility of novel
      gene discovery.

PMID- 24013572
TI  - Reconfiguration of network hub structure after propofol-induced unconsciousness.
AB  - INTRODUCTION: General anesthesia induces unconsciousness along with functional
      changes in brain networks. Considering the essential role of hub structures for
      efficient information transmission, the authors hypothesized that anesthetics
      have an effect on the hub structure of functional brain networks. METHODS: Graph
      theoretical network analysis was carried out to study the network properties of
      21-channel electroencephalogram data from 10 human volunteers anesthetized on two
      occasions. The functional brain network was defined by Phase Lag Index, a
      coherence measure, for three states: wakefulness, loss of consciousness induced
      by the anesthetic propofol, and recovery of consciousness. The hub nodes were
      determined by the largest centralities. The correlation between the altered hub
      organization and the phase relationship between electroencephalographic channels
      was investigated. RESULTS: Topology rather than connection strength of functional
      networks correlated with states of consciousness. The average path length,
      clustering coefficient, and modularity significantly increased after
      administration of propofol, which disrupted long-range connections. In
      particular, the strength of hub nodes significantly decreased. The primary hub
      location shifted from the parietal to frontal region, in association with
      propofol-induced unconsciousness. The phase lead of frontal to parietal regions
      in the alpha frequency band (8-13 Hz) observed during wakefulness reversed
      direction after propofol and returned during recovery. CONCLUSIONS: Propofol
      reconfigures network hub structure in the brain and reverses the phase
      relationship between frontal and parietal regions. Changes in network topology
      are more closely associated with states of consciousness than connectivity and
      may be the primary mechanism for the observed loss of frontal to parietal
      feedback during general anesthesia.

PMID- 24013574
TI  - A clinical investigation of inhibitory effect of panobinostat on CYP2D6 substrate
      in patients with advanced cancer.
AB  - PURPOSE: Panobinostat is a potent oral pan-deacetylase inhibitor with promising
      clinical activity in hematologic malignancies. Panobinostat was shown to inhibit
      CYP2D6 activity in vitro; thus understanding the magnitude of the potential
      clinical inhibition of panobinostat on co-medications that are CYP2D6 substrates
      becomes important. METHODS: This study evaluated the effects of co-administration
      of panobinostat with a sensitive CYP2D6 substrate, dextromethorphan (DM), in
      patients with advanced cancer who have functional CYP2D6 genes. Patients received
      60 mg DM alone on day 1, panobinostat at 20 mg alone on days 3 and 5, and both
      agents on day 8. Plasma concentrations of DM and its metabolite dextrorphan (DX)
      were determined by liquid chromatography-tandem mass spectrometry following
      serial blood collections on day 1 (DM alone) and day 8 (in combination with
      panobinostat). RESULTS: Panobinostat increased DM exposure by 64 % [geometric
      mean ratio (GMR), 1.64 (90 % confidence interval (CI), 1.17-2.31)] and DX
      exposure by 29 % (GMR, 1.29 [90 % CI, 1.10-1.51]). These results indicated that
      panobinostat weakly inhibited a sensitive CYP2D6 substrate in cancer patients by
      increasing DM exposure by less than twofold. CONCLUSION: Safety monitoring of
      sensitive CYP2D6 substrates with narrow therapeutic index is recommended when co
      administering with panobinostat in future clinical practice.

PMID- 24013575
TI  - Inhibition of sorcin reverses multidrug resistance of K562/A02 cells and MCF
      7/A02 cells via regulating apoptosis-related proteins.
AB  - PURPOSE: Sorcin, a 22-kDa calcium-binding protein, renders cancer cells resistant
      to chemotherapeutic agents, thus playing an important role in multidrug
      resistance (MDR). But the mechanisms mediated by sorcin still remain quite
      elusive. This study aim to explore whether sorcin silencing could restore
      chemosensitivity in MDR cancer cells and seek to identify the functional
      mechanisms mediated by sorcin. METHODS: To investigate the mechanisms of sorcin
      silencing-induced chemosensitivity, transient expression of sorcin-siRNAs was
      performed in doxorubicin-induced MDR cell lines, K562/A02 and MCF-7/A02.
      Sensitivity to five chemotherapeutic agents was evaluated by analysis of cell
      survival and cell apoptosis. RESULTS: In this report, we show that down
      regulation of sorcin did not alter expression or function of P-gp, but actually
      induced cell apoptosis and chemosensitivity in K562/A02 and MCF-7/A02. We also
      observe that silencing of sorcin-enhanced chemotherapeutic agent effects partly
      through regulating apoptosis-related protein, including Bcl-2, Bax, c-jun and c
      fos. CONCLUSION: This offers the rationale for the development of therapeutic
      strategies down-regulating sorcin expression for the treatment of cancer,
      especially for the reversal of MDR.

PMID- 24013573
TI  - Primary hepatocytes and their cultures in liver apoptosis research.
AB  - Apoptosis not only plays a key role in physiological demise of defunct
      hepatocytes, but is also associated with a plethora of acute and chronic liver
      diseases as well as with hepatotoxicity. The present paper focuses on the
      modelling of this mode of programmed cell death in primary hepatocyte cultures.
      Particular attention is paid to the activation of spontaneous apoptosis during
      the isolation of hepatocytes from the liver, its progressive manifestation upon
      the subsequent establishment of cell cultures and simultaneously to strategies to
      counteract this deleterious process. In addition, currently applied approaches to
      experimentally induce controlled apoptosis in this in vitro setting for
      mechanistic research purposes and thereby its detection using relevant biomarkers
      are reviewed. 

PMID- 24013576
TI  - Pharmacogenetic determinants associated with sunitinib-induced toxicity and
      ethnic difference in Korean metastatic renal cell carcinoma patients.
AB  - PURPOSE: The aim of this study was to investigate the pharmacogenetic
      determinants of sunitinib-related toxicity and ethnic difference in metastatic
      renal cell carcinoma (mRCC) among Korean patients. METHODS: A pharmacogenetic
      study was performed in 65 patients with mRCC treated with the standard schedule
      of sunitinib (50 mg orally once daily for 4 weeks-on/2 weeks-off). Detailed data
      regarding the toxicity of sunitinib, including thrombocytopenia, neutropenia,
      anemia, and hand-foot syndrome (HFS), were prospectively collected in a clinical
      trial program (n = 38) or standard oncology practice (n = 27). Total of 12
      genetic polymorphisms in 8 candidate genes (CYP1A1, CYP3A5, ABCB1, ABCG2,
      PDGFRalpha, VEGFR2, RET, and FLT3) were analyzed for an association with
      treatment-related toxicity from sunitinib using Pearson chi (2) test. RESULTS:
      Common grade 3 or grade 4 treatment-related toxicities were thrombocytopenia
      (36.9 %, 24/65), neutropenia (18.4 %, 12/65), anemia (7.7 %, 5/65), and HFS (12.3
      %, 8/65). Patients carrying an ABCG2 421 AA genotype developed significantly more
      grade 3 or grade 4 thrombocytopenia, neutropenia, and HFS adjusted for age, sex,
      and Eastern Cooperative Oncology Group performance status, and body surface area
      (odds ratio compared with AC/CC genotypes [OR] 9.90, P = 0.04, thrombocytopenia;
      OR 18.20, P = 0.02, neutropenia; and OR 28.46, P = 0.01, HFS). In addition, total
      and surface protein ABCG2 protein expression was decreased in ABCG2 421 AA mutant
      cells compared to wild type. CONCLUSION: Among 12 genetic polymorphisms,
      polymorphism in the ABCG2 421C>A gene may be mostly associated with the risk of
      sunitinib-related toxicity in mRCC patients. Considering the high frequency of
      421C>A SNP in Asian, this may be related to differential toxicities among ethnic
      groups.

PMID- 24013577
TI  - Penetrating electrode stimulation of the rabbit optic nerve: parameters and
      effects on evoked cortical potentials.
AB  - BACKGROUND: Stimulus parameters, in particular pulse shape, are an important
      consideration in the application of electrical stimulation when experimentally
      testing a visual prosthesis. We changed the biphasic pulse shape of several
      asymmetric charge-balanced pulses to investigate their effect on optic nerve (ON)
      stimulation and the recorded cortical response. METHODS: Monopolar platinum
      iridium electrodes were implanted into the rabbit's ON behind the eyeball.
      Electrical evoked potentials (EEPs) were recorded with silver ball electrodes
      placed on the cortex, and the results quantified. RESULTS: Our results indicate
      that changing the shape of cathodic-first charge-balanced biphasic pulse (CA)
      while maintaining charge balance could reduce the current thresholds for
      stimulation. When stimulated at the same charge density, the stimulus having high
      amplitude short-duration (HASD) cathodic phase produced a higher amplitude
      response, with a larger spatial spread but with a lower current threshold
      compared with other stimuli. Adding an inter-phase gap between the two phases of
      the stimulus increased the EEP amplitude, but was saturated at a gap of ~0.2 ms;
      this was most obvious with CA stimulation, which was able to elicit a larger
      cortical response than that elicited by asymmetrical charge-balanced stimulus
      pulses with HASD cathodic phase, in contrast to CA without a gap. As the
      stimulating frequency increased, the amplitudes of the EEP components elicited by
      CA monotonically decreased. The fastest component (P0) was present with
      stimulating frequencies as high as 80 Hz, while the slower P1 and P2 disappeared
      with stimulating frequencies higher than 40 and 20 Hz, respectively. CONCLUSION:
      A CA stimulus waveform with an inter-phase gap of 0.2 ms was more efficacious for
      ON stimulation than other stimulus combinations, and therefore should result in
      less tissue damage, minimal electrode etching, and lower power consumption if
      used in a visual prosthesis.

PMID- 24013578
TI  - Extraction of retinal tacks from subjects implanted with an epiretinal visual
      prosthesis.
AB  - BACKGROUND: Retinal tacks, first developed for the treatment of complex retinal
      detachments, have more recently been used for the fixation of epiretinal
      electrode arrays as part of implanted visual prostheses. Here, we report on the
      clinical experience of extracting four such tacks after chronic implantation. The
      ability to safely extract retinal tacks ensures that epiretinal devices can be
      repositioned or removed if necessary. METHODS: Custom-built, titanium alloy
      retinal tacks were mechanically removed from the posterior coats after prolonged
      implantation (up to 19 months). The resulting wound was characterized by clinical
      evaluation, fundus photography, and fluorescein angiography while being monitored
      for stability over time. The wounds were also compared to earlier published
      reports of the healing response around retinal tacks in human subjects. RESULTS:
      Tack extraction was accomplished successfully, without complication, in all four
      subjects. The wound site was readily identified by pale scar tissue. No change in
      the wound size or appearance was noted over many months of post-operative
      observation (up to 22 months after explant). No adverse effects on overall ocular
      health were detected. CONCLUSION: Extraction of retinal tacks from subjects
      implanted with epiretinal prostheses can be performed without significant
      complication. The long-term healing response appears to be stable and localized
      in eyes afflicted with retinitis pigmentosa or choroideremia. There was also
      minimal, if any, impact on the local circulatory system. These cases suggest that
      the use of retinal tacks for anchoring epiretinal visual prostheses does not
      preclude safe repositioning or removal of the device more than a year after
      implant.

PMID- 24013580
TI  - Hypertensive choroidopathy with eclampsia viewed on spectral-domain optical
      coherence tomography.
AB  - PURPOSE: We report a case of hypertensive choroidopathy with detailed retinal
      images obtained using spectral-domain optical coherence tomography (SD-OCT).
      CASE: A 19-year-old pregnant woman with no history of high blood pressure had an
      eclamptic seizure at the 39th week of pregnancy; the baby was delivered by
      emergency Caesarean section. Six days later, she presented with bilateral blurred
      vision (best-corrected visual acuity [VA], 0.5, right eye; 0.3, left eye).
      Bilateral extensive, punctate, pale-yellow Elschnig's spots were present in the
      posterior fundus. SD-OCT showed a serous retinal detachment (SRD) and retinal
      pigment epithelium detachment (PED) representing a waveform retinal pigment
      epithelium (RPE) layer in each eye. The reflective intensity decreased partly at
      the waveform RPE. A wavy structure suggestive of fibrin was present in both
      foveas between the photoreceptor ellipsoid zone and the RPE-outer segment line.
      Four weeks after delivery and oral antihypertensive treatment, the SRDs, PEDs and
      wavy structure resolved and the VA recovered. CONCLUSION: SD-OCT visualized SRDs,
      PEDs, wavy structures under the photoreceptor ellipsoid zone, and areas of low
      intensity RPE layer in hypertensive choroidopathy.

PMID- 24013579
TI  - The price for reduced light toxicity: Do endoilluminator spectral filters
      decrease color contrast during Brilliant Blue G-assisted chromovitrectomy?
AB  - BACKGROUND: Vitreoretinal surgeons have been slow to adopt the use of spectral
      filters for endoillumination to reduce retinal light toxicity. This study shows
      that spectral filters can be used without a loss in color contrast during
      brilliant blue G chromovitrectomy. METHODS: To evaluate the influence of intra
      operative spectral light filters on perceivable contrast during Brilliant Blue G
      chromovitrectomy, a prospective, observational clinical study was carried out on
      59 consecutive Brilliant Blue G chromovitrectomy interventions in 59 patients
      admitted for macular holes, macular pucker or vitreomacular traction syndromes.
      Subsequent to peeling of the internal limiting membrane, six different
      illumination modes were enabled consecutively: mercury vapor, mercury
      vapor/xenon, and xenon followed by xenon combined with an amber, green or yellow
      spectral filter. Main outcome measure was the chromaticity spread between stained
      internal limiting membrane and unstained retina as a measure for the color
      contrast perceived by the human eye. RESULTS: Mean chromaticity scores were
      similar for all light sources: mercury vapor 7.97, mercury vapor/xenon 7.96 (p =
      0.96), and xenon 7.41 (p = 0.55). Compared to xenon, the additional use of
      endoillumination spectral filters did not change contrast recognizability:
      Chromaticity scores were 9.38 for the amber filter (p = 0.13), 6.63 for the green
      and 7.02 for the yellow filter (p = 0.37 and 0.64, respectively). When comparing
      the different filters head-to-head, the amber filter was superior to the green
      filter (p = 0.03), while the yellow was intermediate and not significantly
      different from either the amber (p = 0.08) or the green filter (p = 0.51).
      CONCLUSIONS: Color contrast perceptibility during Brilliant Blue G assisted
      chromovitrectomy is similar with mercury vapor, mercury vapor/xenon or xenon
      light sources. Spectral filters do not decrease color contrast recognizability.
      Head-to-head comparison shows a significant advantage for the amber over the
      green filter with respect to contrast generation, the yellow filter is
      intermediate. As spectral filters are known to greatly reduce retinal light
      toxicity, we suggest donor eye studies to validate whether the amber filter
      should be generally recommended for Brilliant Blue G chromovitrectomy.

PMID- 24013581
TI  - Loss of HER2 positivity and prognosis after neoadjuvant therapy in HER2-positive
      breast cancer patients.
AB  - BACKGROUND: Emerging literature data are showing that a change in human epidermal
      growth factor receptor (HER2) status adversely affects breast cancer patient's
      prognosis. The aim of this study was to evaluate the prognostic impact of HER2
      loss in patients with HER2-positive disease treated with neoadjuvant therapy with
      or without anti-HER2 agents. METHODS: One hundred and seven consecutive HER2
      positive patients were identified from a prospectively maintained database. The
      first cohort includes 40 patients treated with chemotherapy (CT) alone. The
      second cohort includes 67 patients treated with neoadjuvant CT plus anti-HER2
      agents (trastuzumab and/or lapatinib). HER2 expression was evaluated by
      immunihistochemistry or fluorescence in situ hybridization on pretreatment core
      biopsy and on surgical specimen after therapy. RESULTS: The rates of pathologic
      complete response (pCR) and breast-conserving surgery were higher in the CT +
      anti-HER2 cohort. A loss of HER2 expression was observed in 40% of the patients
      with residual disease after CT alone versus 14.7% of the patients after CT + anti
      HER2 agents (P = 0.019). Patients not achieving a pCR have a significant increase
      in the risk of relapse when compared with those achieving a pCR (hazard ratio
      [HR] 9.55, P = 0.028). Patients with HER2 loss tended to have a higher risk of
      relapse as comparing to patients with maintained HER2 positivity (HR 2.41, P =
      0.063). CONCLUSION: The pCR is confirmed as a powerful predictor of long-term
      outcome. The rate of HER2 loss is higher in patients receiving neoadjuvant CT
      without anti-HER2 agents. HER2 status on residual disease after preoperative
      therapy can be helpful in selecting patients at different risk of relapse, to be
      included in prospective trial exploring further adjuvant therapy.

PMID- 24013582
TI  - Phase I trial combining temozolomide plus lapatinib for the treatment of brain
      metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM
      trial.
AB  - BACKGROUND: Brain metastases (BMs) pose a clinical challenge in breast cancer
      (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the
      combination of both drugs as treatment for patients with HER2-positive BC and BM.
      METHODS: Eighteen patients were enrolled, with sixteen of them having recurrent
      or progressive BM. Any type of previous therapy was allowed, and disease was
      assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The
      primary end points were the evaluation of the dose-limiting toxicities (DLTs) and
      the determination of the maximum-tolerated dose (MTD). The secondary end points
      included objective response rate, clinical benefit and duration of response.
      RESULTS: The lapatinib-temozolomide regimen showed a favorable toxicity profile
      because the MTD could not be reached. The most common adverse events (AEs) were
      fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out
      of 15 assessable patients. The estimated median survival time for the 16 patients
      with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression
      free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37].
      CONCLUSIONS: The lapatinib-temozolomide combination is well tolerated.
      Preliminary evidence of clinical activity was observed in a heavily pretreated
      population, as indicated by the volumetric reductions occurring in brain lesions.

PMID- 24013583
TI  - A risk analysis for production processes with disposable bioreactors.
AB  - : Quality management systems are, as a rule, tightly defined systems that
      conserve existing processes and therefore guarantee compliance with quality
      standards. But maintaining quality also includes introducing new enhanced
      production methods and making use of the latest findings of bioscience. The
      advances in biotechnology and single-use manufacturing methods for producing new
      drugs especially impose new challenges on quality management, as quality
      standards have not yet been set. New methods to ensure patient safety have to be
      established, as it is insufficient to rely only on current rules. A concept of
      qualification, validation, and manufacturing procedures based on risk management
      needs to be established and realized in pharmaceutical production. The chapter
      starts with an introduction to the regulatory background of the manufacture of
      medicinal products. It then continues with key methods of risk management.
      Hazards associated with the production of medicinal products with single-use
      equipment are described with a focus on bioreactors, storage containers, and
      connecting devices. The hazards are subsequently evaluated and criteria for risk
      evaluation are presented. This chapter concludes with aspects of industrial
      application of quality risk management. 

PMID- 24013585
TI  - Synthesis of carboxylate-functionalized graphene nanosheets for high dispersion
      of platinum nanoparticles based on the reduction of graphene oxide via 1
      pyrenecarboxaldehyde.
AB  - A one-step reduction/functionalization strategy for the synthesis of carboxylate
      functionalized graphene nanosheets is reported in this paper. 1
      pyrenecarboxaldehyde (PCA) is introduced as a new reductant for the chemical
      reduction of graphene oxide (GO), serving three roles: reducing GO to graphene
      nanosheets (GNs), stabilizing the as-prepared GNs due to the electrostatic
      repulsion of the oxidation products of PCA (1-pyrenecarboxylate, PC-) on the
      surface of the GNs and anchoring Pt nanoparticles (Pt NPs) with high dispersion
      and small particle size. Transmission electron microscopy shows that Pt NPs with
      an average diameter of 1.3 +/- 0.2 nm are uniformly dispersed on the surface of
      the PC--functionalized GNs (PC--GNs). The obtained Pt NPs/PC--GNs nanohybrids
      have higher electrocatalytic activity and stability towards methanol oxidation in
      comparison with Pt NPs supported on GNs obtained by the chemical reduction of GO
      with the typical reductant, hydrazine.

PMID- 24013584
TI  - miR-106a-5p inhibits the proliferation and migration of astrocytoma cells and
      promotes apoptosis by targeting FASTK.
AB  - Astrocytomas are common malignant intracranial tumors that comprise the majority
      of adult primary central nervous system tumors. MicroRNAs (miRNAs) are small, non
      coding RNAs (20-24 nucleotides) that post-transcriptionally modulate gene
      expression by negatively regulating the stability or translational efficiency of
      their target mRNAs. In our previous studies, we found that the downregulation of
      miR-106a-5p in astrocytomas is associated with poor prognosis. However, its
      specific gene target(s) and underlying functional mechanism(s) in astrocytomas
      remain unclear. In this study, we used mRNA microarray experiments to measure
      global mRNA expression in the presence of increased or decreased miR-106a-5p
      levels. We then performed bioinformatics analysis based on multiple target
      prediction algorithms to obtain candidate target genes that were further
      validated by computational predictions, western blot analysis, quantitative real
      time PCR, and the luciferase reporter assay. Fas-activated serine/threonine
      kinase (FASTK) was identified as a direct target of miR-106a-5p. In human
      astrocytomas, miR-106a-5p is downregulated and negatively associated with
      clinical staging, whereas FASTK is upregulated and positively associated with
      advanced clinical stages, at both the protein and mRNA levels. Furthermore,
      Kaplan-Meier analysis revealed that the reduced expression of miR-106a-5p or the
      increased expression of FASTK is significantly associated with poor survival
      outcome. These results further supported the finding that FASTK is a direct
      target gene of miR-106a-5p. Next, we explored the function of miR-106a-5p and
      FASTK during astrocytoma progression. Through gain-of-function and loss-of
      function studies, we demonstrated that miR-106a-5p can significantly inhibit cell
      proliferation and migration and can promote cell apoptosis in vitro. The
      knockdown of FASTK induced similar effects on astrocytoma cells as those induced
      by the overexpression of miR-106a-5p. These observations suggest that miR-106a-5p
      functions as a tumor suppressor during the development of astrocytomas by
      targeting FASTK. 

PMID- 24013586
TI  - Heart rate dynamics after combined strength and endurance training in middle-aged
      women: heterogeneity of responses.
AB  - The loss of complexity in physiological systems may be a dynamical biomarker of
      aging and disease. In this study the effects of combined strength and endurance
      training compared with those of endurance training or strength training alone on
      heart rate (HR) complexity and traditional HR variability indices were examined
      in middle-aged women. 90 previously untrained female volunteers between the age
      of 40 and 65 years completed a 21 week progressive training period of either
      strength training, endurance training or their combination, or served as
      controls. Continuous HR time series were obtained during supine rest and
      submaximal steady state exercise. The complexity of HR dynamics was assessed
      using multiscale entropy analysis. In addition, standard time and frequency
      domain measures were also computed. Endurance training led to increases in HR
      complexity and selected time and frequency domain measures of HR variability
      (P<0.01) when measured during exercise. Combined strength and endurance training
      or strength training alone did not produce significant changes in HR dynamics.
      Inter-subject heterogeneity of responses was particularly noticeable in the
      combined training group. At supine rest, no training-induced changes in HR
      parameters were observed in any of the groups. The present findings emphasize the
      potential utility of endurance training in increasing the complex variability of
      HR in middle-aged women. Further studies are needed to explore the combined
      endurance and strength training adaptations and possible gender and age related
      factors, as well as other mechanisms, that may mediate the effects of different
      training regimens on HR dynamics. 

PMID- 24013587
TI  - Changing Parent's Mindfulness, Child Management Skills and Relationship Quality
      With Their Youth: Results From a Randomized Pilot Intervention Trial.
AB  - We evaluated the efficacy of a mindful parenting program for changing parents'
      mindfulness, child management practices, and relationships with their early
      adolescent youth and tested whether changes in parents' mindfulness mediated
      changes in other domains. We conducted a pilot randomized trial with 65 families
      and tested an adapted version of the Strengthening Families Program: For Parent
      and Youth 10-14 that infused mindfulness principles and practices against the
      original program and a delayed intervention control group. Results of pre-post
      analyses of mother and youth-report data showed that the mindful parenting
      program generally demonstrated comparable effects to the original program on
      measures of child management practices and stronger effects on measures of
      mindful parenting and parent-youth relationship qualities. Moreover, mediation
      analyses indicated that the mindful parenting program operated indirectly on the
      quality of parent-youth relationships through changes in mindful parenting.
      Overall, the findings suggest that infusing mindful parenting activities into
      existing empirically validated parenting programs can enhance their effects on
      family risk and protection during the transition to adolescence.

PMID- 24013588
TI  - Rank-based variable selection with censored data.
AB  - A rank-based variable selection procedure is developed for the semiparametric
      accelerated failure time model with censored observations where the penalized
      likelihood (partial likelihood) method is not directly applicable. The new method
      penalizes the rank-based Gehan-type loss function with the l1 penalty. To
      correctly choose the tuning parameters, a novel likelihood-based chi2-type
      criterion is proposed. Desirable properties of the estimator such as the oracle
      properties are established through the local quadratic expansion of the Gehan
      loss function. In particular, our method can be easily implemented by the
      standard linear programming packages and hence numerically convenient. Extensions
      to marginal models for multivariate failure time are also considered. The
      performance of the new procedure is assessed through extensive simulation studies
      and illustrated with two real examples.

PMID- 24013590
TI  - The use of an engineered single chain variable fragment in a localized surface
      plasmon resonance method for analysis of the C-reactive protein.
AB  - A gold nanorod (GNR) based LSPR sensor has been developed for label-free
      detection of C-reactive protein (CRP). The sensor utilizes a single chain
      variable fragment (scFv) as a receptor to bind CRP. The results of this effort
      show that CRP in human serum can be quantitatively detected at lower than 1 ng
      mL(-1). 

PMID- 24013589
TI  - Spleen tyrosine kinase (Syk) regulates systemic lupus erythematosus (SLE) T cell
      signaling.
AB  - Engagement of the CD3/T cell receptor complex in systemic lupus erythematosus
      (SLE) T cells involves Syk rather than the zeta-associated protein. Because Syk
      is being considered as a therapeutic target we asked whether Syk is central to
      the multiple aberrantly modulated molecules in SLE T cells. Using a gene
      expression array, we demonstrate that forced expression of Syk in normal T cells
      reproduces most of the aberrantly expressed molecules whereas silencing of Syk in
      SLE T cells normalizes the expression of most abnormally expressed molecules.
      Protein along with gene expression modulation for select molecules was confirmed.
      Specifically, levels of cytokine IL-21, cell surface receptor CD44, and
      intracellular molecules PP2A and OAS2 increased following Syk overexpression in
      normal T cells and decreased after Syk silencing in SLE T cells. Our results
      demonstrate that levels of Syk affect the expression of a number of enzymes,
      cytokines and receptors that play a key role in the development of disease
      pathogenesis in SLE and provide support for therapeutic targeting in SLE
      patients. 

PMID- 24013591
TI  - A pivoting elliptical training system for improving pivoting neuromuscular
      control and rehabilitating musculoskeletal injuries.
AB  - Knee injuries often occur in pivoting activities but most existing training and
      rehabilitation devices mainly involve sagittal movements. A pivoting elliptical
      training system (PETS) was developed to train and evaluate neuromuscular control
      in pivoting for the purposes of prevention and rehabilitation of musculoskeletal
      injuries. The PETS have capabilities of controlling two footplates individually
      or simultaneously through servomotor control so that the footplates behave like
      two torsional springs with adjustable offset and stiffness, slippery surface, or
      under external perturbations. Feasibility of the PETS in improving pivoting
      neuromuscular control and pivoting neuromechanical properties was demonstrated
      through experiments on healthy subjects, with reduced pivoting instability and
      reaction time, and improved proprioceptive acuity following training. The PETS
      can potentially be used as a therapeutic and research tool to investigate
      mechanisms underlying pivoting-related injuries and train human subjects for
      improving neuromuscular control during risky pivoting activities. 

PMID- 24013592
TI  - Online evaluation of novel choices by simultaneous representation of multiple
      memories.
AB  - Prior experience is critical for decision-making. It enables explicit
      representation of potential outcomes and provides training to valuation
      mechanisms. However, we can also make choices in the absence of prior experience
      by merely imagining the consequences of a new experience. Using functional
      magnetic resonance imaging repetition suppression in humans, we examined how
      neuronal representations of novel rewards can be constructed and evaluated. A
      likely novel experience was constructed by invoking multiple independent memories
      in hippocampus and medial prefrontal cortex. This construction persisted for only
      a short time period, during which new associations were observed between the
      memories for component items. Together, these findings suggest that, in the
      absence of direct experience, coactivation of multiple relevant memories can
      provide a training signal to the valuation system that allows the consequences of
      new experiences to be imagined and acted on. 

PMID- 24013595
TI  - Direct design of 2D RF pulses using matrix inversion.
AB  - Multi-dimensional pulses are frequently used in MRI for applications such as
      targeted excitation, fat-water separation or metabolic imaging with
      hyperpolarised (13)C compounds. For the design, the problem is typically
      separated into the different dimensions. In this work, a method to directly
      design two-dimensional pulses using the small-tip angle approximation is
      introduced based on a direct matrix representation. The numerical problem is
      solved in a single step directly in two dimensions by matrix inversion. Exemplary
      spectral-spatial excitation and spatio-temporal encoding (SPEN) pulses are
      designed and validated. The main benefits of the direct design approach include a
      reduction of artefacts in case of spectral-spatial pulses, a simple and
      straightforward computer implementation and high flexibility in the pulse design.

PMID- 24013593
TI  - Food experience-induced taste desensitization modulated by the Drosophila TRPL
      channel.
AB  - Animals tend to reject bitter foods. However, long-term exposure to some
      unpalatable tastants increases acceptance of these foods. Here we show that
      dietary exposure to an unappealing but safe additive, camphor, caused the fruit
      fly Drosophila melanogaster to decrease camphor rejection. The transient receptor
      potential-like (TRPL) cation channel was a direct target for camphor in gustatory
      receptor neurons, and long-term feeding on a camphor diet led to reversible
      downregulation of TRPL protein concentrations. The turnover of TRPL was
      controlled by an E3 ubiquitin ligase, Ube3a. The decline in TRPL levels and
      increased acceptance of camphor reversed after returning the flies to a camphor
      free diet long term. We propose that dynamic regulation of taste receptors by
      ubiquitin-mediated protein degradation comprises an important molecular mechanism
      that allows an animal to alter its taste behavior in response to a changing food
      environment. 

PMID- 24013596
TI  - Integrated electron microscopy: super-duper resolution.
AB  - Since its inception, electron microscopy (EM) has revealed that cellular
      membranes are organized into structurally distinct subdomains, created by
      localized protein and lipid assemblies to perform specific complex cellular
      functions. Caveolae are membrane subdomains that function as signaling platforms,
      endocytic carriers, sensors of membrane tension, and mechanical stress, as well
      as in lipid homeostasis. They were first discovered almost 60 years ago by
      pioneering electron microscopists. While new and exciting developments in SUPER
      resolution fluorescent light microscopy facilitate studies of the spatial
      organization of fluorescently labeled protein components, these techniques cannot
      reveal the underlying cellular structures. Thus, equally exciting are
      developments in EM: genetically encoded probes for protein localization at sub-10
      nm resolution, more powerful instruments that allow imaging of larger cell
      volumes, and computational methods for reconstructing three-dimensional images.
      Used in combination, as done by Ludwig et al. in the current issue of PLOS
      Biology, these tools reveal high-resolution insights into the composition and
      organization of the caveolae coat and the formation of these specialized
      structures. Together, these advances are contributing to a resurgence in EM.

PMID- 24013594
TI  - Neuropeptide signaling remodels chemosensory circuit composition in
      Caenorhabditis elegans.
AB  - Neural circuits detect environmental changes and drive behavior. The routes of
      information flow through dense neural networks are dynamic, but the mechanisms
      underlying this circuit flexibility are poorly understood. Here, we define a
      sensory context-dependent and neuropeptide-regulated switch in the composition of
      a C. elegans salt sensory circuit. The primary salt detectors, ASE sensory
      neurons, used BLI-4 endoprotease-dependent cleavage to release the insulin-like
      peptide INS-6 in response to large, but not small, changes in external salt
      stimuli. Insulins, signaling through the insulin receptor DAF-2, functionally
      switched the AWC olfactory sensory neuron into an interneuron in the salt
      circuit. Worms with disrupted insulin signaling had deficits in salt attraction,
      suggesting that peptidergic signaling potentiates responses to high salt stimuli,
      which may promote ion homeostasis. Our results indicate that sensory context and
      neuropeptide signaling modify neural networks and suggest general mechanisms for
      generating flexible behavioral outputs by modulating neural circuit composition. 

PMID- 24013597
TI  - Capsular serotypes and multilocus sequence types of bacteremic Klebsiella
      pneumoniae isolates associated with different types of infections.
AB  - We investigated the epidemiology of different serotypes of Klebsiella pneumoniae
      isolates causing bacteremic liver abscess (LA) using multilocus sequence typing
      (MLST). MLST and molecular typing were performed for 41 K1 (19 LA), 37 K2 (5 LA),
      and 33 non-K1/K2 (6 LA) isolates that were derived from a previous one-year K.
      pneumoniae bacteremia cohort. Capsular serotypes and rmpA of these isolates were
      determined by polymerase chain reaction (PCR) methods. Among the 41 K1 isolates,
      39 were ST23 and the remaining two isolates were ST23 single-locus variant. There
      were 11 STs among K2 isolates. ST65 was the most common (n = 10), followed by
      ST86, ST373, and ST375. Only ST65 (n = 3), ST373 (n = 1), and ST375 (n = 1)
      caused LA, and ST65 was a three-locus variant of ST23. For non-K1/K2 isolates,
      the ST types varied widely. ST218 (K57) was the most common type (n = 6, 18 %),
      and it was a single-locus variant of ST23 and caused two cases of LA. The
      existences of rmpA among serotypes varied (100 % for K1, 89 % for K2, and 55 %
      for non-K1/K2). For isolates causing LA, all of them were positive for rmpA. For
      non-K1/K2 isolates causing infections other than LA, the positivity of rmpA
      ranged from 0 % (biliary tree infection) to 67 % (pneumonia). In this one-year
      cohort, all K1 isolates were ST23 or its single-locus variants, but the
      composition of ST types among K2 isolates was quite variable. ST23 and its one-
      (ST1005 and ST218) and three-locus (ST65) variants comprised 80 % of isolates
      causing LA.

PMID- 24013598
TI  - Comparing two approaches for studying symptom clusters: factor analysis and
      structural equation modeling.
AB  - PURPOSE: We investigated alternative ways of understanding the relationships
      among co-occurring symptoms in individuals with advanced cancer. While factor
      analysis has been increasingly used to identify symptom clusters, we argue that
      structural equation modeling is more appropriate because it permits investigating
      and testing of a greater variety of potential causal interconnections among
      symptoms. METHODS: The sample included 82 palliative patients whose symptom
      scores were obtained from a database of the Capital Health Regional Palliative
      Care Program in Alberta, Canada, from 1995 to 2000. Data were analyzed using
      exploratory factor analysis (SPSS PASW 18.0.0, 2009) and compared to previous
      results obtained using structural equation modeling (LISREL 8.8, 2009). RESULTS:
      Factor models failed to fit the covariance data, even though a single factor
      "explained" nearly half the variance. Structural equation models fit the data and
      explained an average of 66 % of the variance in the dependent latent variables.
      The factor analytic estimates were not clinically useful because they failed to
      correspond to the reasonable underlying common causes of the symptoms. Structural
      equation models, on the other hand, incorporated and tested specific clinically
      anticipated causal relationships among the symptoms and changes in those symptoms
      over time. CONCLUSION: We used factor analysis to reanalyze data previously
      investigated with structural equation modeling and found that the structural
      equation models fit the data better and were more interpretable from a clinical
      perspective. We caution that factor models should be tested for consistency with
      the data and critically examined for inconsistencies with clinical understandings
      of the causal foundations of coordinated symptoms.

PMID- 24013599
TI  - Neuropathic and neurocongnitive complications of antiretroviral therapy among HIV
      infected patients.
AB  - The neurologic events related to antiretroviral therapy (ART) in HIV-infected ART
      naive patients are relatively common. Side effects of ART and complications of
      HIV infection may overlap significantly. Establishing etiology of neurologic
      (neuropathy and neuropathic pain, changes in cognition, dementia, and myelopathy)
      and psychiatric (neurocognitive disorders, depression, anxiety, substance abuse
      and dependence, and others) complications can present a significant challenge. It
      has long been documented that neurologic and psychological side effects can occur
      with many of the agents used to treat HIV infection. Particularly, efavirenz from
      the non-nucleoside reverse transcriptase inhibitor (NNRTI) has been associated
      with neurologic and psychological complaints that may be difficult to
      differentiate from pre-existing mental illness, substance abuse, and HIV-related
      neuropsychiatric symptoms. Peripheral neuropathy (PN) of at least 6 different
      types is a well-known adverse effect of treatment with nucleoside reverse
      transcriptase inhibitors (NRTIs) in HIV-infected patients. Lack of dealing with
      early stages of neurologic and psychological side effects of HIV infection and
      Highly Active Anti-retroviral Therapy (HAART) are observed in daily practice. The
      purpose of this article is to identify the neurologic, neuropsychiatric and
      psychiatric complications related to HIV and anti-retroviral therapy, to discuss
      current knowledge about these disorders, and to suggest strategies for their
      diagnosis and management. 

PMID- 24013600
TI  - The psychosocial conditions and intensified education that may affect school
      performance of HIV/AIDS orphaned children on antiretroviral drugs.
AB  - OBJECTIVE: This study begins with interpreting basic academic results from the
      House of Family (HOF) comprehensive project for HIV/AIDS orphaned children. We
      reviewed school performance during the academic period from 2007 to 2012.
      METHODS: All the children in the HOF project have vertically acquired HIV
      infection, with approximately 90% being with AIDS/Clinical Stage C at the time of
      admission. Initiation of antiretroviral drugs (ARV) was at the average age of 7
      (mean 6.94, median 6.5, and a mode of 6). In the year 2007, 44 children had been
      receiving ARV. The majority of these children 32 (72.7%) were on ARV for at least
      1 year, 6 (13.6%) of the children on ARV for 4 years, 7 (15.9%) were on ARV for 3
      years, 5 (11.3%) for 2 years, 14 (31.8%) for 1 year, and 12 (27.2%) started ARV
      on that year. Later on, an additional 2 children started ARV in 2008, 1 child in
      2009, and 4 children in 2010. RESULTS: We found that the total number of children
      achieving a certain academic level changed very little between each scholastic
      year. During the four years of school reviewed, it was noted that the Poor
      performers made improvement and an increase in Good performance grades was also
      achieved. The trend of Fair levels remained mostly unchanged at 65%, 70.2%,
      68.5%, and 64.6% respectively. The overall passing performance, including both
      Fair and Good scores, improved from 67.5% in 2008 to 80.8% the following year of
      school. This passing rate of 80.8% in 2009 remains stable over the next two years
      at 80.3% and 80.3% respectively. CONCLUSION: Despite the late introduction of ARV
      medicine, limited family and social support, and deficient academic achievement,
      the children of HOF were able to improve their school performance due to
      intensified psychosocial and educational support provided at the HOF
      comprehensive project.

PMID- 24013601
TI  - Sleeping sickness in Buikwe South Health sub-district: Neuroinfection situation
      report.
AB  - OBJECTIVE: The aim of this paper is to describe the incidence of Trypanosoma
      brucei rhodesiense sleeping sickness in the last functioning treatment centre in
      Buikwe South HSD in Southeast Uganda, in Mukono District, for a 19-year period
      (1989-2008). This is a report on the treatment outcome, structure of population
      affected, comparison with the published data on general incidence of T. b
      rhodesiensae in Uganda and functioning of sleeping sickness control program.
      METHODS: Cross-sectional sleeping sickness data from 1989 to 2008 were collected
      retrospectively in 2009 at Buikwe Sleeping Sickness Center to identify case
      counts and measures of disease magnitude per sub-county per year. Data were
      collected from all available records of sleeping sickness patients. Case counts
      from the Buikwe South sub-counties, and even some neighboring sub-counties for 19
      years (1989-2008) were collected and analyzed by Microsoft Excel and EpiInfo
      program. RESULTS: In the period from 1989 to 2008, 372 cases of sleeping sickness
      were diagnosed and treated. Children under 5 years were 12 (3.22%) - males 6,
      females 6, patients in the age from 6 to 15 years were 51 (13.7%) - males 30,
      females 21, and patients above 15 were 309 (83.06%) - males 176, females 133. In
      the category 5-15 years and above 15 years there was a significant gender
      difference closely connected to the professional exposure. The oldest patient was
      80 years old, the youngest was 3 moths old. The average age of the patients was
      30.8 years. From all 372 patients with trypanosomiasis 30 had died - 10 females
      and 20 males, which means 8% case fatality. The case fatality rate in the late
      stage of the disease was 14%. From this group 6 patients (20%) had negative BS.
      The average interval between the diagnosis and death was 14.4 days, in 10
      patients the exact date of death was not recorded. Average age of the patients
      that died was 30.6 years. CONCLUSION: Sleeping sickness still remains a serious
      public health problem. Since the preventive and educational activities for the
      control of this neglected disease are not functioning, it very easily can re
      emerge. In the future, it is also essential to support the research of less toxic
      drugs, further research and interventions related to parasite transmission
      through cattle movements and potential changes in vector-human exposure in
      central Ugandan districts as well as strengthening of the necessary, relevant
      surveillance systems.

PMID- 24013602
TI  - Tropical neuroinfections in south sudanese rural hospitals - analysis of 8,709
      patients.
AB  - OBJECTIVE: Infections involving the central nervous system have very serious
      consequences and affect thousands of people in Africa. Despite the availability
      of new antibiotics and vaccines, neuroinfections act as dangerous and life
      threatening conditions. The most frequent neuroinfections which are of the
      greatest importance for public health systems are viral diseases (such as HIV,
      encephalitis, poliomyelitis, rabies), bacterial diseases (bacterial meningitis,
      neurological complications of leprosy and tuberculosis) and parasitic infections
      (cerebral malaria, sleeping sickness, trypanosomiasis, schistosomiasis,
      toxoplasmosis etc.). METHODS: A descriptive study to assess the occurrence of
      neuroinfections in two rural hospitals in Sudan (Mapuordit in Yirol and Gordim in
      Aweil) was performed in two periods of two years: (i) 2005-2006 and (ii) 2010
      2011. We obtained data on patients from Mapuordit and from Gordim by studying
      their medical records. RESULTS: Several cases of neuroinfections were observed
      during both periods; those were represented by tetanus, meningococcal meningitis,
      leprosy with neuropathy (altogether 442 patients) in Mapuordit. Also in Gordim,
      severe neuroinfections such as cerebral malaria were very rare (1 case), as well
      as tetanus (1 case), meningococcal meningitis (8 cases) and sleeping sickness (9
      cases). However, the incidence of neuroinfections decreased from 44/1000 in 2005
      2006 to 2/1000 in 2010-2011. CONCLUSIONS: Decreased incidence of serious
      neuroinfections (cerebral malaria, sleeping sickness, meningococcal meningitis)
      in Sudan may be related to improvement of effective therapeutic options,
      represented by (i) intermittent preventive therapy (IPT) for malaria, (ii) by
      suppression of sleeping sickness vectors and (iii) by better accessibility of
      antibiotics.

PMID- 24013603
TI  - Neurologic complications and sequellae of infectious diseases in Uganda and
      Kenya: Analysis of 288 cases from two rural hospitals.
AB  - OBJECTIVE: Many infections occurring in area of Sub-Saharan Africa are associated
      with more or less serious neurologic symptoms or complications. The aim of this
      study was to assess the incidence of selected infectious diseases in the
      equatorial part of Uganda and Kenya and to monitor potential neurological
      complications of these infections. METHODS: The study was performed for May -
      August 2008. Patients suffering from cerebral malaria, AIDS, meningitis, typhoid,
      tuberculosis (TB), syphilis, leprosy, and trypanosomiasis patients were enrolled.
      Besides of standard examination, lumbar puncture (LP) and cerebrospinal fluid
      (CSF) examination was performed, and the occurrence of neurological disorders and
      sequellae was recorded and assessed. RESULTS: Altogether 288 patients with
      neurological manifestation were enrolled. Malaria was the most prevalent disease
      in this study (102 cases, 35.42%), followed by typhoid (47 cases, 16.2%) and
      meningitis (38 cases, 13.2%). Leprosy and trypanosomiasis were only rarely
      detected (2.3% and 1.4%, respectively). CONCLUSION: In malaria and HIV hyper
      endemic area of rural Uganda, cerebral malaria is the leading tropical
      neuroinfection. Also, meningitis is still frequent probably due to insufficient
      access to vaccination.

PMID- 24013605
TI  - Neurologic disorders in HIV-positive orphans: 10 years of follow up.
AB  - OBJECTIVE: Neuropsychic manifestations of AIDS are still noticeable especially in
      developing countries. The aim of this short communication is to describe
      psychological, behavioral and neurologic disorders caused by either HIV-related
      disorders, or drug related toxicities in HIV-infected children from Cambodia
      (Phnom Penh, Sihanoukville) treated during 10 years with highly active
      antiretroviral therapy (HAART). METHODS: One hundred and thirty seven (137) HIV
      positive children (age 2-19 years) treated with HAART since 2003 (6-10 years
      follow up) have been analyzed concerning opportunistic infections, other co
      infections, renal parameters, hematologic parameters, chest X-ray, antiretroviral
      treatment, anti-tuberculotics and antibiotics treatment. We recorded
      prospectively all data since the start of HAART from 2003-2005 up to December
      2012. RESULTS: Occurrence of drug related neuritis due to stavudine (HAART) was
      less than 1% and was associated with anti-tuberculous agents accompanying HAART
      in HIV- and tuberculosis co-infected patients. Co-infections with neurotropic
      viruses were more frequent: 1 case of CMV retinitis, 18 cases of herpes zoster
      neuritis and 37 cases of generalized HZV infections (varicella), after onset
      HAART in children were recorded. All children responded well to anti-viral
      therapy with ganciclovir (CMV), vanciclovir or acyclovir (HZV) in combination
      with first line HAART. CONCLUSION: Neurologic disorders in children with HAART
      are less frequent than in adults. Anti-retrovirals and anti-tuberculosis drugs
      seem to be safe and less toxic in children then in adults. Co-infections with
      neurotropic viruses were more frequent, however, were successfully treated with
      anti-virals.

PMID- 24013604
TI  - Fungal neuroinfections and fungaemia: unexpected increase of mortality from
      invasive fungal infections in 2005-2011 in comparison to 1989-1998: analysis of
      210 cases.
AB  - OBJECTIVE: In this short communication we compared the data of fungaemia cases in
      Slovak hospitals from 1989-1998 published in 1999-2000 with data from 2005-2011.
      METHODS: Risk factors, etiology and outcome of fungaemia between two periods
      (1989-1998 vs. 2005-2011) were compared and risk factors for death assessed by
      univariate analysis (CDC 2006 Statistical Package). RESULTS: In comparison to
      1989-1998 when only amphotericin B and fluconazole has been used (55%), in 2005
      2011 only 35.2% patients received FLU, but 26.4% received voriconazole, 22%
      caspofungin and anidulafungin and about 6.6% lipid formulations of Amphotericin
      B. In etiology, while in 1989-1998 only 37.1% (115/310) represented non-albicans
      Candida (NAC) and non-Candida yeasts in 2005-2011 already reached 63.7%. The
      significant increase of breakthrough fungaemia may be a sign of inappropriate
      empiric therapy.

PMID- 24013606
TI  - Malaria in hyperendemic region of Uganda has seasonal variations and is
      associated with low mortality.
AB  - OBJECTIVE: Majority of malaria cases in hyper-endemic areas have seasonal
      variations. The aim of this short research note is to refer and assess seasonal
      variability and mortality of malaria in Ngogwe in southeast Uganda in 2011/2012
      season. METHODS: We analyzed clinical records of patients admitted to Buikwe
      Ngogwe Hospital in the period from July 1, 2011 to August 25, 2012 to assess
      seasonality of malaria. RESULTS: Altogether, 23,675 patients were admitted to
      Buikwe-Ngogwe Hospital due to fever illness and 14,940 malaria-positive samples
      were obtained (63.1%) from these patients. We have observed significantly higher
      number of malaria cases in December compared to period of June - November
      (p<0.01). Mortality rate was only 0.48%. CONCLUSION: Interestingly, we have
      observed seasonal variability in malaria occurrence in Ngogwe, Southeast Uganda,
      which is, not correlating with rainy season but with movement of population to
      the areas closer to Lake Victoria. However, despite of high prevalence, mortality
      of this disease remained low. The reasons for low mortality are probably a good
      access to health care facility and adaptation of artemisinin-based combinational
      therapy for documented malaria.

PMID- 24013607
TI  - Numbers of non-severe as well as cerebral malaria cases are decreasing with
      higher altitude in Burundi Highlands, but still remains high.
AB  - OBJECTIVE: We aimed to assess the occurrence of malaria-positive cases in 4 rural
      Burundian hospitals during December 2011 placed at different altitudes above sea
      level. METHODS: Diagnosis of malaria was made upon considering clinical symptoms,
      microscopic evaluation and rapid diagnostic test results. We performed analysis
      of patient's clinical data collected in 4 hospitals in Burundi to compare the
      occurrence of malaria at different altitudes. RESULTS: The lowest incidence of
      malaria during December 2011 was detected at Murago Hospital (606 cases per
      month, 47.6%), which is located in the highest altitude, and the highest
      occurrence was in Gasura (1,559 cases, 91.3%), then in Rutovu (732 cases, 81.2%)
      and Buraniro (4,436 cases, 78.6%). Compared with other types of consultations
      (gynecological, HIV/AIDS, other tropical diseases), malaria was the most frequent
      reason for medical consultation. CONCLUSION: We have observed the lowest
      occurrence of malaria at hospitals located in the highest altitude. Despite the
      lower number of malaria cases in higher altitudes, its impact on public health
      should not be underestimated.

PMID- 24013608
TI  - Cerebral malaria complicated with coma, multiorgan failure and psychosocial
      sequellae observed among non-immune travelers to Benin, Sudan and Madagascar.
AB  - OBJECTIVE: Severe malaria represents less than 10% of all malaria cases and is
      associated with significant mortality. The aim of this case series was to review
      severe malaria cases in travelers within the last 10 years in Slovakia. METHODS:
      All cases of severe malaria in travelers reported within last 10 years from the
      Inpatient Department in Slovakia to the Slovak Tropical Institute (STI) are
      reviewed. Only those traveling as tourist to Sub-Saharan Africa were included.
      RESULTS: During the last 10 years, eight (n=8) cases of cerebral malaria were
      reported, of which only one died (12.5%). Seven of all 8 cases had deep coma
      (87.5%), 4 (50%) required ventilator support, 4 (50%) required dialysis, 5
      (62.5%) had liver failure and 6 (75%) had severe acidosis. CONCLUSION: Severe
      malarial cases were rarely detected among travelers returning to Slovakia within
      last 10 years. In survivors usually no sequellae remained. One patient treated
      with quinine alone died.

PMID- 24013609
TI  - Imported tropical neuroinfections: practice skills and knowledge among nurses and
      nursing students.
AB  - OBJECTIVE: Tropical neuroinfections are still cause of substantial mortality in
      travelers. Therefore, good knowledge of early symptoms is very important for
      nurses acting as first contact persons. METHODS: Nurse's practical skills and
      knowledge of signs and early recognition of tropical neuroinfections, providing
      first aid and quick action has been studied among graduates of two Tropical
      Nursing PhD programs (in EU-Countries vs. tropical country) using a standardized
      questionnaire. Statistical package EPI info was used to determine potential
      differences between both groups of graduates. RESULTS: Acceptable knowledge on
      early symptoms and signs of cerebral malaria and meningococcal meningitis in
      returning travelers was found among 121 graduates of two PhD programs who were
      included in the study. Of these, 99 questionnaires were filled in Slovakia, Czech
      Republic and Germany and another 22 were filled in Malaysia, as a part of the
      Tropical Nursing PhD Study Programs. CONCLUSION: Nursing students and recent
      graduates in two PhD programs demonstrated acceptable, although not large-scaled,
      knowledge of early signs and symptoms of tropical neuroinfections.

PMID- 24013610
TI  - A double-blind, placebo controlled, randomized trial of riluzole as an adjunct to
      risperidone for treatment of negative symptoms in patients with chronic
      schizophrenia.
AB  - RATIONALE: Several recent studies have focused on glutamate modulating agents for
      symptoms relief in schizophrenia, especially negative symptoms which are
      resistant to conventional therapies. OBJECTIVES: We aimed to assess the efficacy
      and tolerability of riluzole, an anti-glutamate agent with neuroprotective
      properties, as an adjunct to risperidone in improving negative symptoms of
      schizophrenia. METHODS: In this randomized double-blind placebo-controlled
      parallel-group study, 50 patients with chronic schizophrenia and a score of >=20
      on the negative subscale of positive and negative syndrome scale (PANSS) were
      enrolled in the active phase of their illness. Participants were equally
      randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone
      (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The
      primary outcome of this study was the difference in the decrease of PANSS
      negative subscale score from baseline to the study endpoint between the two
      groups. RESULTS: By the study endpoint, riluzole-treated patients showed
      significantly greater improvement in the negative symptoms (P < 0.001) as well as
      the PANSS total and general psychopathology subscale scores (P = 0.001 and P <
      0.001; respectively) compared to the placebo group. Treatment group was the only
      significant predictor of changes in negative symptom in this trial (beta = -0.56,
      P < 0.001). No significant difference was observed between two groups in the
      frequency of side effects. CONCLUSION: These preliminary findings suggest that
      riluzole may be a safe and effective medication for the treatment of negative
      symptoms in patients with chronic schizophrenia. Further research and replication
      of study findings is warranted. Clinical trial registry name and registration
      number: Iranian registry of clinical trials www.irct.ir , IRCT201107281556N26

PMID- 24013611
TI  - Saccharomyces cerevisiae mutants affected in vacuole assembly or vacuolar H+
      ATPase are hypersensitive to lead (Pb) toxicity.
AB  - Lead is an important environmental pollutant. The role of vacuole, in Pb
      detoxification, was studied using a vacuolar protein sorting mutant strain
      (vps16Delta), belonging to class C mutants. Cells disrupted in VPS16 gene, did
      not display a detectable vacuolar-like structure. Based on the loss of cell
      proliferation capacity, it was found that cells from vps16Delta mutant exhibited
      a hypersensitivity to Pb-induced toxicity, compared to wild type (WT) strain. The
      function of vacuolar H(+)-ATPase (V-ATPase), in Pb detoxification, was evaluated
      using mutants with structurally normal vacuoles but defective in subunits of
      catalytic (vma1Delta or vma2Delta) or membrane domain (vph1Delta or vma3Delta) of
      V-ATPase. All mutants tested, lacking a functional V-ATPase, displayed an
      increased susceptibility to Pb, comparatively to cells from WT strain.
      Modification of vacuolar morphology, in Pb-exposed cells, was visualized using a
      Vma2p-GFP strain. The treatment of yeast cells with Pb originated the fusion of
      the medium size vacuolar lobes into one enlarged vacuole. In conclusion, it was
      found that vacuole plays an important role in the detoxification of Pb in
      Saccharomyces cerevisiae; in addition, a functional V-ATPase was required for Pb
      compartmentalization. 

PMID- 24013612
TI  - Identification and evaluation of reference genes for qRT-PCR normalization in
      Ganoderma lucidum.
AB  - Quantitative real-time reverse transcription PCR (qRT-PCR) is a rapid, sensitive,
      and reliable technique for gene expression studies. The accuracy and reliability
      of qRT-PCR results depend on the stability of the reference genes used for gene
      normalization. Therefore, a systematic process of reference gene evaluation is
      needed. Ganoderma lucidum is a famous medicinal mushroom in East Asia. In the
      current study, 10 potential reference genes were selected from the G. lucidum
      genomic data. The sequences of these genes were manually curated, and primers
      were designed following strict criteria. The experiment was conducted using qRT
      PCR, and the stability of each candidate gene was assessed using four commonly
      used statistical programs-geNorm, NormFinder, BestKeeper, and RefFinder.
      According to our results, PP2A was expressed at the most stable levels under
      different fermentation conditions, and RPL4 was the most stably expressed gene in
      different tissues. RPL4, PP2A, and beta-tubulin are the most commonly recommended
      reference genes for normalizing gene expression in the entire sample set. The
      current study provides a foundation for the further use of qRT-PCR in G. lucidum
      gene analysis. 

PMID- 24013614
TI  - Colloidal stability and thermo-responsive properties of iron oxide nanoparticles
      coated with polymers: advantages of Pluronic(r) F68-PEG mixture.
AB  - Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized to be an
      attractive platform for developing novel drug delivery approaches and thus
      several types of functionalized magnetic nanocarriers based on SPIONs have been
      synthesized and studied. The coating of the metal oxide surface was achieved in a
      one-pot synthesis with biocompatible polyethylene glycol (PEG) and thermo
      responsive modified Pluronic(r) F68. The resulting thermo-responsive magnetic
      nanocarriers can incorporate water insoluble drugs into their hydrophobic
      compartment and later release them in a temperature dependent manner. Here we
      report novel magnetic nanocarriers with significant improvements regarding the
      colloidal stability and critical temperature obtained by mixing various molar
      ratios of hydrophilic PEG with thermo-responsive Pluronic(r) F68 bearing
      different end group functionalities. Various methods have been employed to
      characterize the magnetic nanocarriers, such as photon correlation spectroscopy
      (DLS), atomic absorption, FT-IR spectroscopy, and surface-enhanced Raman
      scattering. The transition temperature that determines changes in the
      conformation of the block copolymer chain was studied by DLS as a function of
      temperature. Moreover, the drug loading properties of SPION-(F68-OMe)-(F68-FA)
      and SPION-PEG-F68-FA were analyzed with a hydrophobic fluorescent dye, DID oil.
      The behavior of the encapsulated DID into the nanocarrier shell was studied as a
      function of temperature via fluorescence spectroscopy. These results offer
      original insights into the enhanced colloidal stability and thermo-sensitive
      properties of the novel synthesized magnetic nanocarriers.

PMID- 24013613
TI  - [Minimally invasive abdominothoracic esophagus resection by transoral
      esophagogastrostomy: interdisciplinary challenge].
AB  - BACKGROUND: Resection of the esophagus is an invasive 2-cavitiy procedure which
      requires special anesthesiological expertise during perioperative care.
      Furthermore, in surgery new minimally invasive techniques are continually being
      established which place special challenges on the treatment team because the
      anesthesiologist is decisively involved in the course of surgery. AIM: The aim of
      this article is to present the development of surgical treatment options for
      esophageal cancer starting from classical open resection up to the minimally
      invasive technique of esophagectomy (MIE). Previous experience with MIE on a
      cohort of patients is presented and the special anesthesiological characteristics
      of this innovative technique are illustrated. MATERIAL AND METHODS: In the
      department for general, visceral and transplantation surgery of the University
      Medical Center of Mainz, minimally invasive abdominothoracic esophageal resection
      has been carried out since 2010. High thoracic anastomization was performed using
      the EEATM-OrVilTM system operated by the anesthesiologist. Currently 17 highly
      selected patients have been surgically treated using this technique. RESULTS:
      Esophagogastric anastomosis with the EEATM-OrVilTM system was feasible in all
      patients. Transoral introduction of the gastric probe with the connecting sheath
      and the angled anvil led to minor dislocation of the double lumen tube in only
      one patient and could immediately be corrected. Further intraoperative
      complications did not occur. Four of the 17 patients developed pneumonia which
      could be controlled by intravenous antibiotics. None of the patients had to be
      reintubated. One patient developed gastric tube necrosis and died 51 days
      postoperatively due to massive intracerebral hemorrhage. There were no
      complications of anastomoses following OrVilTM anastomization. In all patients an
      R0 resection could be achieved. CONCLUSION: Minimally invasive esophagectomy with
      transoral anastomization appears to be an enrichment of the minimally invasive
      spectrum as interdisciplinary cooperation leads to reduced operation time and a
      more efficient process of anastomization. This also results in decreased one-lung
      ventilation time which is directly correlated to postoperative pulmonary
      complications. In particular, the interdisciplinary character of this technique
      and the necessity for targeted communication proved to be of assistance also in
      other situations.

PMID- 24013615
TI  - Correction of nonlinear lateral distortions of scanning probe microscopy images.
AB  - A methodology for the correction of scanning probe microscopy image distortions
      is demonstrated. It is based on the determination of displacement vectors from
      the measurement of a calibration sample. By moving the pixels of the distorted
      scanning probe microscopy image along the displacement vectors an almost complete
      correction of the nonlinear, time independent distortions is achieved. 

PMID- 24013616
TI  - Matrix-free dynamic nuclear polarization enables solid-state NMR 13C-13C
      correlation spectroscopy of proteins at natural isotopic abundance.
AB  - We introduce a general approach for dynamic nuclear polarization (DNP) enhanced
      solid-state NMR that overcomes the current problems in DNP experiments caused by
      the use of frozen solutions. Notably, we report for the first time a 2D (13)C
      (13)C correlation spectrum of a protein without the use of isotopic labeling. 

PMID- 24013617
TI  - Evaluation of left ventricular diastolic function in nonhypertensive nondiabetic
      hemodialysis patients.
AB  - AIM: Diastolic dysfunction (DD) is common in hemodialysis (HD) patients. Because
      diabetes mellitus (DM) and hypertension (HT) are also common in this patient
      group, the exact reason for DD in HD patients is not clear. The present study
      evaluated left ventricular (LV) diastolic function in HD patients without DM and
      HT. METHODS: Fifty patients on HD and 34 age-matched and sex-matched healthy
      control individuals were enrolled. Echocardiography was performed in all
      participants. LV systolic and diastolic functions were evaluated by B-mode
      echocardiography, pulsed wave, and tissue Doppler imaging. The HD patients were
      divided into two groups according to the presence or absence of left ventricular
      hypertrophy (LVH) in echocardiography. RESULTS: LV dimensions and systolic
      function were within normal limits and similar between groups. However, the HD
      patients had significantly worse diastolic function (E/A: 0.78 +/- 0.26 vs. 1.19
      +/- 0.28, P < 0.001, e'/a' septal: 0.77 +/- 0.36 vs. 1.04 +/- 0.21, P < 0.001)
      and increased filling pressure (E/e': 8.55 +/- 3.2 vs. 5.79 +/- 1.93, P < 0.001).
      Thirty-one (62%) patients had LVH, whereas 19 (38%) patients did not have LVH. LV
      systolic and diastolic functions were similar in HD patients with and without
      LVH. Seventeen (55%) hypertrophies were concentric and 14 (45%) were eccentric.
      Diastolic functions were similar in patients with either concentric or eccentric
      hypertrophy. CONCLUSION: Diastolic function is impaired in HD patients even in
      the absence of diseases that can cause DD such as HT and DM.

PMID- 24013618
TI  - Validation of the A&D UA-1020 upper-arm blood pressure monitor with six different
      shaped or different-sized cuffs according to the British Hypertension Society
      protocol.
AB  - OBJECTIVE: The present study aimed to evaluate the accuracy of the automated
      oscillometric upper-arm blood pressure monitor A&D UA-1020 with six different
      shaped or different-sized cuffs according to the British Hypertension Society
      protocol. METHODS: We recruited 136 individuals for four D-ring cuffs (adult,
      large, small, and medium) and 114 individuals for two cylindrical cuffs (adult
      and medium). For each participant, we sequentially measured systolic and
      diastolic blood pressure using a mercury sphygmomanometer (two observers) and UA
      1020 (one supervisor) to obtain three pairs of comparisons. RESULTS: For the four
      D-ring cuffs, the device achieved grade A. The percentage of blood pressure
      differences within 5, 10, and 15 mmHg was 64, 88, and 96%, respectively, for
      systolic blood pressure, and 69, 92, and 99%, respectively, for diastolic blood
      pressure. The average (+/- SD) of the device-observers differences was -1.2 +/-
      7.2 mmHg (P = 0.0006) and 1.0 +/- 6.0 mmHg (P < 0.0001) for systolic and
      diastolic blood pressure, respectively. For the two cylindrical cuffs, the device
      also achieved grade A. The percentage of blood pressure differences within 5, 10,
      and 15 mmHg was 65, 87, and 96%, respectively, for systolic blood pressure, and
      64, 91, and 98%, respectively, for diastolic blood pressure. The average of the
      device-observers differences was -0.4 +/- 7.3 mmHg (P = 0.29) and 2.0 +/- 6.1
      mmHg (P < 0.0001) for systolic and diastolic blood pressure, respectively.
      CONCLUSION: The UA-1020 device has passed the requirements of the British
      Hypertension Society protocol with various sizes of D-ring and cylindrical cuffs,
      and can be recommended in adults.

PMID- 24013619
TI  - No relationship between biopsy sites near the main testicular vessels or rete
      testis and successful sperm retrieval using conventional or microdissection
      biopsies in 220 non-obstructive azoospermic men.
AB  - In 220 consecutive patients with non-obstructive azoospermia, sperm retrieval was
      attempted by a combination of conventional and microdissection testicular sperm
      extraction (TESE). For sperm retrieval, 2-3 conventional biopsies were performed
      followed by a microdissection TESE in cases of negative conventional biopsies.
      During the surgery, the vasculature of the testis was assessed using the
      operative microscope, and the location of positive biopsies was registered in
      relation to the blood supply. The overall sperm retrieval rate was 58.2%. From
      the initial conventional biopsies, sperm could be retrieved in 46.8% of the
      patients. With microdissection TESE, sperm could be retrieved from an additional
      11.4% of the patients. The further use of microdissection TESE improved the sperm
      retrieval rate significantly (P=0.017). No significant accumulation of positive
      biopsies was found towards the rete testis or the main testicular vessels.

PMID- 24013620
TI  - A rare complication of a malleable penile prosthesis: migration to the thigh
      region.

PMID- 24013621
TI  - Characterisation of Lyzls in mice and antibacterial properties of human LYZL6.
AB  - C-type lysozyme genes (Lyzls) belong to the class of lysozymes and are highly
      expressed in the testis and epididymis. The members Lyzl4 and Spaca3 have been
      reported to play a role in sperm-egg binding and fertilisation in mice. However,
      the function of the remaining two mouse c-type lysozyme genes, Lyzl1 and Lyzl6,
      is still not clear. In the present study, we analysed the tissue expression and
      androgen-dependent expression of mouse c-type lysozyme genes and the possible
      contribution of human recombinant LYZL6 (rLYZL6) to immunity. The expression of
      Lyzls was detected by RT-PCR, Western blots, immunohistochemistry and
      immunofluorescence. The bacteriolytic activity of rLYZL6 was analysed by a colony
      forming assay. In mice, the expression of Lyzl genes was mainly in the testis and
      epididymis in a developmentally regulated manner and androgen- or testicular
      factor-regulated manner. Immunodetection revealed the presence of LYZL6 protein
      in primary spermatocytes and round spermatids of the testis and on the post
      acrosomal area and midpiece of mature epididymal spermatozoa. The rLYZL6 protein
      exhibited antibacterial activity. From the results, Lyzls may play a role in
      mitochondrial function of spermatozoa and LYZL6 may contribute to the innate
      immunity of the male genital tract.

PMID- 24013622
TI  - The effects of folate-conjugated gold nanorods in combination with plasmonic
      photothermal therapy on mouth epidermal carcinoma cells.
AB  - The use of lasers has emerged to be highly promising for cancer therapy
      modalities, most commonly, the photothermal therapy method. Unfortunately, the
      most common disadvantage of laser therapy is its nonselectivity and requirement
      of high power density. The use of plasmonic nanoparticles as highly enhanced
      photoabsorbing agents has thus introduced a much more selective and efficient
      cancer therapy strategy. In this study, we aimed to demonstrate the selective
      targeting and destruction of mouth epidermal carcinoma cells (KB cells) using the
      photothermal therapy of folate-conjugated gold nanorods (F-GNRs). Considering the
      beneficial characteristics of GNRs and overexpression of the folate receptor by
      KB cells, we selected F-GNRs as a targeted photothermal therapy agent. Cell
      viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Apoptosis was determined by flow cytometry
      using an annexin V-fluorescein isothiocyanate/propidium iodide apoptosis
      detection kit. No cell damage or cytotoxicity from the individual treatment of
      laser light or F-GNRs was observed. However, a 56% cell lethality was achieved
      for KB cells using combined plasmonic photothermal therapy of 20 MUM F-GNRs with
      seven pulses of laser light and 6-h incubation periods. Cell lethality strongly
      depends on the concentration of F-GNRs and the incubation period that is mainly
      due to the induction of apoptosis. This targeted damage is due to the F-GNRs
      present in the cancer cells strongly absorbing near-infrared laser light and
      rapidly converting it to heat. This new therapeutic avenue for cancer therapy
      merits further investigation using in vivo models for application in humans.

PMID- 24013624
TI  - Effects of laser therapy on the proliferation of human periodontal ligament stem
      cells.
AB  - Low-level laser irradiation (LLLI) stimulates the proliferation of a variety of
      cell types. However, very little is known about the effect of laser therapy on
      dental stem cells. The aim of the present study was to evaluate the effect of
      LLLI (660 nm, 30 mW) on the proliferation rate of human periodontal ligament stem
      cells (hPDLSC), obtained from two healthy permanent third molars extracted due to
      surgical indication. Culture cells were either irradiated or not (control) with
      an InGaAIP diode laser at 0 and 48 h, using two different energy densities (0.5
      J/cm2, 16 s and 1.0 J/cm2, 33 s). Cell proliferation was evaluated by the Trypan
      blue exclusion method and by measuring mitochondrial activity using the MTT-based
      cytotoxicity assay at intervals of 0, 24, 48, and 72 h after the first laser
      application. An energy density of 1.0 J/cm2 improved the cell proliferation in
      comparison to the other groups (control and laser 0.5 J/cm2) at 48 and 72 h. The
      group irradiated with 1.0 J/cm2 presented significantly higher MTT activity at 48
      and 72 h when compared to the energy density of 0.5 J/cm2. It can be concluded
      that LLLI using infrared light and an energy density of 1.0 J/cm2 has a positive
      stimulatory effect on the proliferation of hPDLSC.

PMID- 24013623
TI  - Thermocycling effect on microshear bond strength to zirconia ceramic using Er:YAG
      and tribochemical silica coating as surface conditioning.
AB  - The purpose of this study is to evaluate the thermocycling effect on the
      microshear bond strength (MUSBS) of different self-adhesive resin cements to
      zirconia using tribochemical silica coating RocatecTM (ROC) and Er:YAG as surface
      conditioners. Two hundred forty square-like zirconia samples were polished and
      randomly assigned in four groups according surface treatment applied as follows:
      (1) no treatment (NT), (2) silica coating with ROC, 3) Er:YAG laser irradiation
      (LAS: 2.940 nm, 200 mJ; 10 Hz), and (4) laser followed by RocatecTM (LAROC). Each
      group was divided into two subgroups according the resin tested as follows: (A)
      BiFix SE (BIF) and (B) Clearfil SA (CLE). After 24 h, half of the specimens from
      each subgroup were tested. The other half was stored and thermocycled (5-55 
      degrees C/5,000 cycles). A MUSBS test was performed using a universal testing
      machine (cross head speed = 0.5 mm/min). Failure modes were recorded and observed
      by scanning electronic microscopy. Data was analyzed with ANOVA, Student's t
      test, and chi-square tests, and linear regression was performed (p < 0.05).
      Before thermocycling, both cements showed higher MUSBS results with ROC and
      LAROC. After aging, (1) all BIF specimens evidenced severely decreased adhesion
      with mostly adhesive failures and (2) CLE maintained the initial results in ROC
      and LAROC groups, performing better with ROC. Thermocycling did not negatively
      influence the resin-zirconia MUSBS results in the self-adhesive resin cement
      containing 10-MDP when used on zirconia surface coated with silica, independently
      of previous Er:YAG surface treatment. 

PMID- 24013625
TI  - Targeted therapy by gene transfer of a monovalent antibody fragment against the
      Met oncogenic receptor.
AB  - Due to the key role played in critical sub-populations, Met is considered a
      relevant therapeutic target for glioblastoma multiforme and lung cancers. The
      anti-Met DN30 antibody, engineered to a monovalent Fab (Mv-DN30), proved to be a
      potent antagonist, inducing physical removal of Met receptor from the cell
      surface. In this study, we designed a gene therapy approach, challenging Mv-DN30
      in preclinical models of Met-driven human glioblastoma and lung carcinoma. Mv
      DN30 was delivered by a Tet-inducible-bidirectional lentiviral vector. Gene
      therapy solved the limitations dictated by the short half-life of the low
      molecular weight form of the antibody. In vitro, upon doxycycline induction, the
      transgene: (1) drove synthesis and secretion of the correctly assembled Mv-DN30;
      (2) triggered the displacement of Met receptor from the surface of target cancer
      cells; (3) suppressed the Met-mediated invasive growth phenotype. Induction of
      transgene expression in cancer cells-transplanted either subcutaneously or
      orthotopically in nude mice-resulted in inhibition of tumor growth. Direct Mv
      DN30 gene transfer in nude mice, intra-tumor or systemic, was followed by a
      therapeutic response. These results provide proof of concept for a gene transfer
      immunotherapy strategy by a Fab fragment and encourage clinical studies targeting
      Met-driven cancers with Mv-DN30. KEY MESSAGE: Gene transfer allows the continuous
      in vivo production of therapeutic Fab fragments. Mv-DN30 is an excellent tool for
      the treatment of Met-driven cancers. Mv-DN30 gene therapy represents an
      innovative route for Met targeting.

PMID- 24013626
TI  - Role for cis-acting RNA sequences in the temperature-dependent expression of the
      multiadhesive lig proteins in Leptospira interrogans.
AB  - The spirochete Leptospira interrogans causes a systemic infection that provokes a
      febrile illness. The putative lipoproteins LigA and LigB promote adhesion of
      Leptospira to host proteins, interfere with coagulation, and capture complement
      regulators. In this study, we demonstrate that the expression level of the LigA
      and LigB proteins was substantially higher when L. interrogans proliferated at 37
      degrees C instead of the standard culture temperature of 30 degrees C. The RNA
      comprising the 175-nucleotide 5' untranslated region (UTR) and first six lig
      codons, whose sequence is identical in ligA and ligB, is predicted to fold into
      two distinct stem-loop structures separated by a single-stranded region. The
      ribosome-binding site is partially sequestered in double-stranded RNA within the
      second structure. Toeprint analysis revealed that in vitro formation of a 30S
      tRNA(fMet)-mRNA ternary complex was inhibited unless a 5' deletion mutation
      disrupted the second stem-loop structure. To determine whether the lig sequence
      could mediate temperature-regulated gene expression in vivo, the 5' UTR and the
      first six codons were inserted between the Escherichia coli l-arabinose promoter
      and bgaB (beta-galactosidase from Bacillus stearothermophilus) to create a
      translational fusion. The lig fragment successfully conferred thermoregulation
      upon the beta-galactosidase reporter in E. coli. The second stem-loop structure
      was sufficient to confer thermoregulation on the reporter, while sequences
      further upstream in the 5' UTR slightly diminished expression at each temperature
      tested. Finally, the expression level of beta-galactosidase was significantly
      higher when point mutations predicted to disrupt base pairs in the second
      structure were introduced into the stem. Compensatory mutations that maintained
      base pairing of the stem without restoring the wild-type sequence reinstated the
      inhibitory effect of the 5' UTR on expression. These results indicate that ligA
      and ligB expression is limited by double-stranded RNA that occludes the ribosome
      binding site. At elevated temperatures, the ribosome-binding site is exposed to
      promote translation initiation. 

PMID- 24013627
TI  - Identification and characterization of non-cellulose-producing mutants of
      Gluconacetobacter hansenii generated by Tn5 transposon mutagenesis.
AB  - The acs operon of Gluconacetobacter is thought to encode AcsA, AcsB, AcsC, and
      AcsD proteins that constitute the cellulose synthase complex, required for the
      synthesis and secretion of crystalline cellulose microfibrils. A few other genes
      have been shown to be involved in this process, but their precise role is
      unclear. We report here the use of Tn5 transposon insertion mutagenesis to
      identify and characterize six non-cellulose-producing (Cel(-)) mutants of
      Gluconacetobacter hansenii ATCC 23769. The genes disrupted were acsA, acsC, ccpAx
      (encoding cellulose-complementing protein [the subscript "Ax" indicates genes
      from organisms formerly classified as Acetobacter xylinum]), dgc1 (encoding
      guanylate dicyclase), and crp-fnr (encoding a cyclic AMP receptor
      protein/fumarate nitrate reductase transcriptional regulator). Protein blot
      analysis revealed that (i) AcsB and AcsC were absent in the acsA mutant, (ii) the
      levels of AcsB and AcsC were significantly reduced in the ccpAx mutant, and (iii)
      the level of AcsD was not affected in any of the Cel(-) mutants. Promoter
      analysis showed that the acs operon does not include acsD, unlike the
      organization of the acs operon of several strains of closely related
      Gluconacetobacter xylinus. Complementation experiments confirmed that the gene
      disrupted in each Cel(-) mutant was responsible for the phenotype. Quantitative
      real-time PCR and protein blotting results suggest that the transcription of
      bglAx (encoding beta-glucosidase and located immediately downstream from acsD)
      was strongly dependent on Crp/Fnr. A bglAx knockout mutant, generated via
      homologous recombination, produced only ~16% of the wild-type cellulose level.
      Since the crp-fnr mutant did not produce any cellulose, Crp/Fnr may regulate the
      expression of other gene(s) involved in cellulose biosynthesis. 

PMID- 24013628
TI  - The transfer-messenger RNA-small protein B system plays a role in avian
      pathogenic Escherichia coli pathogenicity.
AB  - Extraintestinal pathogenic Escherichia coli (ExPEC) is capable of colonizing
      outside of the intestinal tract and evolving into a systemic infection. Avian
      pathogenic E. coli (APEC) is a member of the ExPEC group and causes avian
      colibacillosis. Transfer-mRNA-small protein B (tmRNA-SmpB)-mediated trans
      translation is a bacterial translational control system that directs the
      modification and degradation of proteins, the biosynthesis of which has stalled
      or has been interrupted, facilitating the rescue of ribosomes stalled at the 3'
      ends of defective mRNAs that lack a stop codon. We found that disruption of one,
      or both, of the smpB or ssrA genes significantly decreased the virulence of the
      APEC strain E058, as assessed by chicken infection assays. Furthermore, the
      mutants were obviously attenuated in colonization and persistence assays. The
      results of quantitative real-time reverse transcription-PCR analysis indicated
      that the transcription levels of the transcriptional regulation gene rfaH and the
      virulence genes kpsM, chuA, and iss were significantly decreased compared to
      those of the wild-type strain. Macrophage infection assays showed that the mutant
      strains reduced the replication and/or survival ability in the macrophage HD11
      cell line compared to that of the parent strain, E058. However, no significant
      differences were observed in ingestion by macrophages and in chicken serum
      resistance between the mutant and the wild-type strains. These data indicate that
      the tmRNA-SmpB system is important in the pathogenesis of APEC O2 strain E058. 

PMID- 24013629
TI  - The Clostridium perfringens germinant receptor protein GerKC is located in the
      spore inner membrane and is crucial for spore germination.
AB  - The Gram-positive, anaerobic, spore-forming bacterium Clostridium perfringens
      causes a variety of diseases in both humans and animals, and spore germination is
      thought to be the first stage of C. perfringens infection. Previous studies have
      indicated that the germinant receptor (GR) proteins encoded by the bicistronic
      gerKA-gerKC operon as well as the proteins encoded by the gerKB and gerAA genes
      are required for normal germination of C. perfringens spores. We now report the
      individual role of these GR proteins by analyzing the germination of strains
      carrying mutations in gerKA, gerKC, or both gerKB and gerAA. Western blot
      analysis was also used to determine the location and numbers of GerKC proteins in
      spores. Conclusions from this work include the following: (i) gerKC mutant spores
      germinate extremely poorly with KCl, l-asparagine, a mixture of asparagine and
      KCl, or NaPi; (ii) gerKC spores germinate significantly more slowly than wild
      type and other GR mutant spores with a 1:1 chelate of Ca(2+) and dipicolinic acid
      and very slightly more slowly with dodecylamine; (iii) the germination defects in
      gerKC spores are largely restored by expressing the wild-type gerKA-gerKC operon
      in trans; (iv) GerKC is required for the spores' viability, almost certainly
      because of the gerKC spores' poor germination; and (v) GerKC is located in the
      spores' inner membrane, with ~250 molecules/spore. Collectively, these results
      indicate that GerKC is the main GR protein required for nutrient and nonnutrient
      germination of spores of C. perfringens food-poisoning isolates. 

PMID- 24013630
TI  - Characterization of fructose 1,6-bisphosphatase and sedoheptulose 1,7
      bisphosphatase from the facultative ribulose monophosphate cycle methylotroph
      Bacillus methanolicus.
AB  - The genome of the facultative ribulose monophosphate (RuMP) cycle methylotroph
      Bacillus methanolicus encodes two bisphosphatases (GlpX), one on the chromosome
      (GlpX(C)) and one on plasmid pBM19 (GlpX(P)), which is required for
      methylotrophy. Both enzymes were purified from recombinant Escherichia coli and
      were shown to be active as fructose 1,6-bisphosphatases (FBPases). The FBPase
      negative Corynebacterium glutamicum Deltafbp mutant could be phenotypically
      complemented with glpX(C) and glpX(P) from B. methanolicus. GlpX(P) and GlpX(C)
      share similar functional properties, as they were found here to be active as
      homotetramers in vitro, activated by Mn(2+) ions and inhibited by Li(+), but
      differed in terms of the kinetic parameters. GlpX(C) showed a much higher
      catalytic efficiency and a lower Km for fructose 1,6-bisphosphate (86.3 s(-1) mM(
      1) and 14 +/- 0.5 MUM, respectively) than GlpX(P) (8.8 s(-1) mM(-1) and 440 +/-
      7.6 MUM, respectively), indicating that GlpX(C) is the major FBPase of B.
      methanolicus. Both enzymes were tested for activity as sedoheptulose 1,7
      bisphosphatase (SBPase), since a SBPase variant of the ribulose monophosphate
      cycle has been proposed for B. methanolicus. The substrate for the SBPase
      reaction, sedoheptulose 1,7-bisphosphate, could be synthesized in vitro by using
      both fructose 1,6-bisphosphate aldolase proteins from B. methanolicus. Evidence
      for activity as an SBPase could be obtained for GlpX(P) but not for GlpX(C).
      Based on these in vitro data, GlpX(P) is a promiscuous SBPase/FBPase and might
      function in the RuMP cycle of B. methanolicus. 

PMID- 24013631
TI  - Two DHH subfamily 1 proteins in Streptococcus pneumoniae possess cyclic di-AMP
      phosphodiesterase activity and affect bacterial growth and virulence.
AB  - Cyclic di-AMP (c-di-AMP) and cyclic di-GMP (c-di-GMP) are signaling molecules
      that play important roles in bacterial biology and pathogenesis. However, these
      nucleotides have not been explored in Streptococcus pneumoniae, an important
      bacterial pathogen. In this study, we characterized the c-di-AMP-associated genes
      of S. pneumoniae. The results showed that SPD_1392 (DacA) is a diadenylate
      cyclase that converts ATP to c-di-AMP. Both SPD_2032 (Pde1) and SPD_1153 (Pde2),
      which belong to the DHH subfamily 1 proteins, displayed c-di-AMP
      phosphodiesterase activity. Pde1 cleaved c-di-AMP into phosphoadenylyl adenosine
      (pApA), whereas Pde2 directly hydrolyzed c-di-AMP into AMP. Additionally, Pde2,
      but not Pde1, degraded pApA into AMP. Our results also demonstrated that both
      Pde1 and Pde2 played roles in bacterial growth, resistance to UV treatment, and
      virulence in a mouse pneumonia model. These results indicate that c-di-AMP
      homeostasis is essential for pneumococcal biology and disease. 

PMID- 24013632
TI  - Porins increase copper susceptibility of Mycobacterium tuberculosis.
AB  - Copper resistance mechanisms are crucial for many pathogenic bacteria, including
      Mycobacterium tuberculosis, during infection because the innate immune system
      utilizes copper ions to kill bacterial intruders. Despite several studies
      detailing responses of mycobacteria to copper, the pathways by which copper ions
      cross the mycobacterial cell envelope are unknown. Deletion of porin genes in
      Mycobacterium smegmatis leads to a severe growth defect on trace copper medium
      but simultaneously increases tolerance for copper at elevated concentrations,
      indicating that porins mediate copper uptake across the outer membrane.
      Heterologous expression of the mycobacterial porin gene mspA reduced growth of M.
      tuberculosis in the presence of 2.5 MUM copper by 40% and completely suppressed
      growth at 15 MUM copper, while wild-type M. tuberculosis reached its normal cell
      density at that copper concentration. Moreover, the polyamine spermine, a known
      inhibitor of porin activity in Gram-negative bacteria, enhanced tolerance of M.
      tuberculosis for copper, suggesting that copper ions utilize endogenous outer
      membrane channel proteins of M. tuberculosis to gain access to interior cellular
      compartments. In summary, these findings highlight the outer membrane as the
      first barrier against copper ions and the role of porins in mediating copper
      uptake in M. smegmatis and M. tuberculosis. 

PMID- 24013633
TI  - Finely tuned regulation of the aromatic amine degradation pathway in Escherichia
      coli.
AB  - FeaR is an AraC family regulator that activates transcription of the tynA and
      feaB genes in Escherichia coli. TynA is a periplasmic topaquinone- and copper
      containing amine oxidase, and FeaB is a cytosolic NAD-linked aldehyde
      dehydrogenase. Phenylethylamine, tyramine, and dopamine are oxidized by TynA to
      the corresponding aldehydes, releasing one equivalent of H2O2 and NH3. The
      aldehydes can be oxidized to carboxylic acids by FeaB, and (in the case of
      phenylacetate) can be further degraded to enter central metabolism. Thus,
      phenylethylamine can be used as a carbon and nitrogen source, while tyramine and
      dopamine can be used only as sources of nitrogen. Using genetic, biochemical and
      computational approaches, we show that the FeaR binding site is a TGNCA-N8-AAA
      motif that occurs in 2 copies in the tynA and feaB promoters. We show that the
      coactivator for FeaR is the product rather than the substrate of the TynA
      reaction. The feaR gene is upregulated by carbon or nitrogen limitation, which we
      propose reflects regulation of feaR by the cyclic AMP receptor protein (CRP) and
      the nitrogen assimilation control protein (NAC), respectively. In carbon-limited
      cells grown in the presence of a TynA substrate, tynA and feaB are induced,
      whereas in nitrogen-limited cells, only the tynA promoter is induced. We propose
      that tynA and feaB expression is finely tuned to provide the FeaB activity that
      is required for carbon source utilization and the TynA activity required for
      nitrogen and carbon source utilization. 

PMID- 24013634
TI  - D-alanine modification of a protease-susceptible outer membrane component by the
      Bordetella pertussis dra locus promotes resistance to antimicrobial peptides and
      polymorphonuclear leukocyte-mediated killing.
AB  - Bordetella pertussis is the causative agent of pertussis, a highly contagious
      disease of the human respiratory tract. Despite very high vaccine coverage,
      pertussis has reemerged as a serious threat in the United States and many
      developing countries. Thus, it is important to pursue research to discover
      unknown pathogenic mechanisms of B. pertussis. We have investigated a previously
      uncharacterized locus in B. pertussis, the dra locus, which is homologous to the
      dlt operons of Gram-positive bacteria. The absence of the dra locus resulted in
      increased sensitivity to the killing action of antimicrobial peptides (AMPs) and
      human phagocytes. Compared to the wild-type cells, the mutant cells bound higher
      levels of cationic proteins and peptides, suggesting that dra contributes to AMP
      resistance by decreasing the electronegativity of the cell surface. The presence
      of dra led to the incorporation of d-alanine into an outer membrane component
      that is susceptible to proteinase K cleavage. We conclude that dra encodes a
      virulence-associated determinant and contributes to the immune resistance of B.
      pertussis. With these findings, we have identified a new mechanism of surface
      modification in B. pertussis which may also be relevant in other Gram-negative
      pathogens. 

PMID- 24013636
TI  - Development of a direct ELISA based on carboxy-terminal of penicillin-binding
      protein BlaR for the detection of beta-lactam antibiotics in foods.
AB  - beta-Lactam antibiotics, including penicillins and cephalosporins, are commonly
      used in veterinary medicine. Illegal use and abuse of beta-lactams could cause
      allergy and selected bacterial resistance. BlaR-CTD, the carboxy-terminal of
      penicillin-recognizing protein BlaR from Bacillus licheniformis ATCC 14580, was
      utilized in this study to develop a receptor-based ELISA for detection and
      determination of beta-lactam antibiotics in milk, beef, and chicken. This assay
      was based on directly competitive inhibition of binding of horseradish peroxidase
      labeled ampicillin to the immobilized BlaR-CTD by beta-lactams. The assay was
      developed as screening test with the option as semiquantitative assay, when the
      identity of a single type of residual beta-lactam was known. The IC50 values of
      15 beta-lactam antibiotics, including benzylpenicillin, ampicillin, amoxicillin,
      dicloxacillin, oxacillin, nafcillin, cefapirin, cefoperazone, cefalotin,
      cefazolin, cefquinome, ceftriaxone, cefotaxime, cefalexin, ceftiofur and its
      metabolite desfuroylceftiofur were evaluated and ranged from 0.18 to 170.81 MUg
      L(-1). Simple sample extraction method was carried out with only phosphate
      buffered saline, and the recoveries of selected beta-lactam antibiotics in milk,
      beef, and chicken were in the range of 53.27 to 128.29 %, most ranging from 60 to
      120 %. The inter-assay variability was below 30 %. Limits of detection in milk,
      beef, and chicken muscles with cefquinome matrix calibration were 2.10, 30.68,
      and 31.13 MUg kg(-1), respectively. This study firstly established a rapid,
      simple, and accurate method for simultaneous detection of 15 beta-lactams in
      edible tissues, among which 11 beta-lactams controlled by European Union could be
      detected below maximum residue limits.

PMID- 24013635
TI  - A comparison of measurement methods and sexual dimorphism for digit ratio (2D:4D)
      in Han ethnicity.
AB  - The digit ratio (2D:4D) is sexually dimorphic and has been considered an
      indicator of prenatal sex hormone exposure. Previous studies have shown that
      males tend to have lower 2D to 4D ratio than females, and this sexual dimorphism
      has been reported across different ethnic groups and different countries.
      However, digit ratio data are missing from the Han ethnicity in China.
      Furthermore, most of the previous studies used direct measurement for digit
      ratio. In this article, we used multiple measurement methods, including the
      direct measurement and two X-ray measurement methods to examine the trait of
      2D:4D in Chinese Han. Our sample consisted of 128 men and 122 women from Liaoning
      Medical University. They were 18-20 years old. The direct measurement and two
      types of X-ray measurements of the length of their 2nd and 4th fingers were used
      separately to calculate digit ratios. Soft tissue thickness of 2D and 4D
      fingertips were also assessed from the two X-ray methods. The results suggest
      that (1) sex differences in 2D:4D tend to be stronger in the two X-ray
      measurements in comparison to the direct measurement; (2) 2D:4D ratios from X-ray
      measurements tend to be lower than that from the direct measurement; (3) Han
      ethnicity have a lower mean value of 2D:4D than other ethnic groups; (4) no sex
      difference in the soft tissue of finger tips. In conclusion, the digit ratio is
      lower in both men and women in Han, and the sexual dimorphism in digit ratio was
      stronger with X-ray measurements in comparison to the direct measurement.

PMID- 24013637
TI  - Gas chromatography-tandem mass spectrometry analysis of 52 monohydroxylated
      metabolites of polycyclic aromatic hydrocarbons in hairs of rats after controlled
      exposure.
AB  - A method based on gas chromatography-tandem mass spectrometry after
      derivatization with N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide was
      developed for the analysis of monohydroxylated polycyclic aromatic hydrocarbons
      (OH-PAHs) in hair. The method focused on 52 target compounds corresponding to two
      to six-ring monohydroxylated metabolites of polycyclic aromatic hydrocarbons
      (PAHs). The limits of quantification ranged from 0.2 to 50 pg mg(-1). The method
      was then applied to the analysis of hair samples collected from rats exposed to
      12 PAHs at 0.01, 0.1, and 1 mg kg(-1), by intraperitoneal injection, for 28 days.
      The results of this study confirm that these metabolites can be incorporated in
      hair after intraperitoneal administration of the corresponding parent compound.
      Only 20 of the 52 metabolites were actually detected in hair samples and
      corresponded to nine parent PAHs. The mean concentrations of OH-PAHs in rat hair
      samples exposed to PAHs at 1 mg kg(-1) ranged from 0.6 +/- 0.2 pg mg(-1) for 8
      hydroxybenzo[b]fluoranthene to 6.7 +/- 1.0 pg mg(-1) for 1-hydroxypyrene. The
      results also demonstrated that hair pigmentation has no influence on the
      concentration of most OH-PAHs. This animal experiment confirmed the incorporation
      of PAH metabolites in hair and demonstrated that the method was sufficiently
      sensitive to detect low levels of exposure to PAHs. These results confirmed the
      usefulness of hair analysis in the biomonitoring of human exposure to PAHs.

PMID- 24013638
TI  - A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute
      lymphoblastic leukemia.
AB  - Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as
      BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL),
      but inherited mutations of PAX5 have not previously been described. Here we
      report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the
      octapeptide domain of PAX5 that was found to segregate with disease in two
      unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all
      affected individuals in both families exhibited 9p deletion, with loss of
      heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional
      sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting
      Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated
      that it had significantly reduced transcriptional activity. These data extend the
      role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5
      in a new syndrome of susceptibility to pre-B cell neoplasia. 

PMID- 24013640
TI  - The genome of the hydatid tapeworm Echinococcus granulosus.
AB  - Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is
      responsible for considerable human morbidity and mortality. This cosmopolitan
      disease is difficult to diagnose, treat and control. We present a draft genomic
      sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with
      the genome sequences from other taxa show that E. granulosus has acquired a
      spectrum of genes, including the EgAgB family, whose products are secreted by the
      parasite to interact and redirect host immune responses. We also find that genes
      in bile salt pathways may control the bidirectional development of E. granulosus,
      and sequence differences in the calcium channel subunit EgCavbeta1 may be
      associated with praziquantel sensitivity. Our study offers insights into host
      interaction, nutrient acquisition, strobilization, reproduction, immune evasion
      and maturation in the parasite and provides a platform to facilitate the
      development of new, effective treatments and interventions for echinococcosis
      control. 

PMID- 24013641
TI  - Flax and Breast Cancer: A Systematic Review.
AB  - BACKGROUND: Flax is a food and dietary supplement commonly used for menopausal
      symptoms. Flax is known for its lignan, alpha-linolenic acid, and fiber content,
      components that may possess phytogestrogenic, anti-inflammatory, and hormone
      modulating effects, respectively. We conducted a systematic review of flax for
      efficacy in improving menopausal symptoms in women living with breast cancer and
      for potential impact on risk of breast cancer incidence or recurrence. METHODS:
      We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to
      January 2013 for human interventional or observational data pertaining to flax
      and breast cancer. RESULTS: Of 1892 records, we included a total of 10 studies: 2
      randomized controlled trials, 2 uncontrolled trials, 1 biomarker study, and 5
      observational studies. Nonsignificant (NS) decreases in hot flash symptomatology
      were seen with flax ingestion (7.5 g/d). Flax (25 g/d) increased tumor apoptotic
      index (P< .05) and decreased HER2 expression (P< .05) and cell proliferation (Ki
      67 index; NS) among newly diagnosed breast cancer patients when compared with
      placebo. Uncontrolled and biomarker studies suggest beneficial effects on hot
      flashes, cell proliferation, atypical cytomorphology, and mammographic density,
      as well as possible anti-angiogenic activity at doses of 25 g ground flax or 50
      mg secoisolariciresinol diglycoside daily. Observational data suggests
      associations between flax and decreased risk of primary breast cancer (adjusted
      odds ratio [AOR] = 0.82; 95% confidence interval [CI] = 0.69-0.97), better mental
      health (AOR = 1.76; 95% CI = 1.05-2.94), and lower mortality (multivariate hazard
      ratio = 0.69; 95% CI = 0.50-0.95) among breast cancer patients. CONCLUSIONS:
      Current evidence suggests that flax may be associated with decreased risk of
      breast cancer. Flax demonstrates antiproliferative effects in breast tissue of
      women at risk of breast cancer and may protect against primary breast cancer.
      Mortality risk may also be reduced among those living with breast cancer.

PMID- 24013639
TI  - Systematic identification of trans eQTLs as putative drivers of known disease
      associations.
AB  - Identifying the downstream effects of disease-associated SNPs is challenging. To
      help overcome this problem, we performed expression quantitative trait locus
      (eQTL) meta-analysis in non-transformed peripheral blood samples from 5,311
      individuals with replication in 2,775 individuals. We identified and replicated
      trans eQTLs for 233 SNPs (reflecting 103 independent loci) that were previously
      associated with complex traits at genome-wide significance. Some of these SNPs
      affect multiple genes in trans that are known to be altered in individuals with
      disease: rs4917014, previously associated with systemic lupus erythematosus
      (SLE), altered gene expression of C1QB and five type I interferon response genes,
      both hallmarks of SLE. DeepSAGE RNA sequencing showed that rs4917014 strongly
      alters the 3' UTR levels of IKZF1 in cis, and chromatin immunoprecipitation and
      sequencing analysis of the trans-regulated genes implicated IKZF1 as the causal
      gene. Variants associated with cholesterol metabolism and type 1 diabetes showed
      similar phenomena, indicating that large-scale eQTL mapping provides insight into
      the downstream effects of many trait-associated variants. 

PMID- 24013642
TI  - Decalepis hamiltonii inhibits tumor progression and metastasis by regulating the
      inflammatory mediators and nuclear factor kappaB subunits.
AB  - Metastasis is an extremely complex process that is a major problem in the
      management of cancer. In the present study, we had evaluated the antimetastatic
      activity of DECALEPIS HAMILTONI: using B16F-10 melanoma-induced experimental lung
      metastasis in a C57BL/6 mice model. D HAMILTONI: treatment significantly ( : <
      .01) inhibited lung tumor nodule formation and reduced the lung collagen
      hydroxyproline, hexosamine, and uronic acid levels. Similarly serum sialic acid
      and gamma-glutamyl transpeptidase levels were also significantly inhibited after
      D HAMILTONI: treatment. The levels of proinflammatory cytokines such as tumor
      necrosis factor alpha, interleukin (IL)-1beta, IL-6, granulocyte monocyte colony
      stimulating factor, and IL-2 in the serum of these animals were significantly
      altered after D HAMILTONI: treatment. The serum NO level was also found to be
      significantly decreased after D HAMILTONI: treatment. This decreased NO level
      after D HAMILTONI: treatment was also accompanied by decreased inducible NO
      synthase and cyclooxygenase-2 expression. The study reveals that D HAMILTONI:
      treatment could alter proinflammatory cytokine production and could inhibit the
      activation and nuclear translocation of p65 and p50 subunits of nuclear factor
      kappaB in B16F-10 cells.

PMID- 24013643
TI  - Markers Are Shared Between Adipogenic and Osteogenic Differentiated Mesenchymal
      Stem Cells.
AB  - The stem cell differentiation paradigm is based on the progression of cells
      through generations of daughter cells that eventually become restricted and
      committed to one lineage resulting in fully differentiated cells. Herein, we
      report on the differentiation of adult human mesenchymal stem cells (hMSCs)
      towards adipogenic and osteogenic lineages using established protocols. Lineage
      specific geneswere evaluated by quantitative real-time PCR relative to two
      reference genes. The expression of osteoblast-associated genes (alkaline
      phosphatase, osteopontin, and osteocalcin)was detected in hMSCs that underwent
      adipogenesis. When normalized, the expression of adipocyte marker genes
      (adiponectin, fatty acid binding protein P4, and leptin) increasedin a time
      dependent manner during adipogenic induction. Adiponectin and leptin were also
      detected in osteoblast-induced cells. Lipid vacuoles that represent the adipocyte
      phenotype were only present in the adipogenic induction group. Conforming to the
      heterogeneous nature of hMSCs and the known plasticity between osteogenic and
      adipogenic lineages, these data indicatea marker overlap between MSC-derived
      adipocytes and osteoblasts. Weproposea careful consideration of experimental
      conditions such as investigated timepoints, selected housekeeping genesand the
      evidence indicating lack of differentiation into other lineageswhen evaluating
      hMSC differentiation.

PMID- 24013644
TI  - Least Absolute Relative Error Estimation.
AB  - Multiplicative regression model or accelerated failure time model, which becomes
      linear regression model after logarithmic transformation, is useful in analyzing
      data with positive responses, such as stock prices or life times, that are
      particularly common in economic/financial or biomedical studies. Least squares or
      least absolute deviation are among the most widely used criterions in statistical
      estimation for linear regression model. However, in many practical applications,
      especially in treating, for example, stock price data, the size of relative
      error, rather than that of error itself, is the central concern of the
      practitioners. This paper offers an alternative to the traditional estimation
      methods by considering minimizing the least absolute relative errors for
      multiplicative regression models. We prove consistency and asymptotic normality
      and provide an inference approach via random weighting. We also specify the error
      distribution, with which the proposed least absolute relative errors estimation
      is efficient. Supportive evidence is shown in simulation studies. Application is
      illustrated in an analysis of stock returns in Hong Kong Stock Exchange.

PMID- 24013645
TI  - The burden of OASIS increases along with socioeconomic position--register-based
      analysis of 980,733 births in Finland.
AB  - BACKGROUND: Obstetric anal sphincter injury (OASIS) has been identified as a
      major preventable risk factor for anal incontinence. OBJECTIVE: Aim was to
      measure national variation in incidence of OASIS by socioeconomic status (SES).
      METHODS: A retrospective population based case-control study using the data
      derived from the Finnish Medical Birth Register for the years 1991-2010. A total
      population of singleton vaginal births was reviewed. We calculated unadjusted
      incidences of OASIS stratified by SES and vaginal parity, and adjusted risks for
      OASIS in each social class, after controlling for parity, birthweight, mode of
      delivery, maternal age and maternal smoking. SES was recorded into five
      categories based on mother's occupation at time of birth; upper white-collar
      workers such as physicians, lower white-collar workers such as nurses, blue
      collar workers such as cleaners, others such as students, and cases with missing
      information. RESULTS: Seven per thousand (6,404 of 980,733) singleton births were
      affected by OASIS. In nulliparae the incidence of OASIS was 18% higher (adjusted
      OR 1.18 95% CI 1.04-1.34) for upper white-collar workers and 12% higher (adjusted
      OR 1.12 95% CI 1.02-1.24) for lower white-collar workers compared with blue
      collar workers. Among women in these higher SES groups, 40% of the excess OASIS
      risk was explained by age, non-smoking, birthweight and mode of delivery. Despite
      the large effect of SES on OASIS, inclusion of SES in multivariable models caused
      only small changes in estimated adjusted effects for other established risk
      factors. CONCLUSIONS: OASIS at the first vaginal delivery demonstrates a strong
      positive social gradient. Higher SES is associated with a number of risk factors
      for OASIS, including higher birthweight and non-smoking, but only 40% of the
      excess incidence is explained by these known risk factors. Further research
      should address other underlying causes including differences in lifestyle or
      environmental factors, and inequalities in healthcare provision.

PMID- 24013646
TI  - The JAK inhibitor, tofacitinib, reduces the T cell stimulatory capacity of human
      monocyte-derived dendritic cells.
AB  - OBJECTIVE: Tofacitinib, which is a Janus kinase (JAK) inhibitor, has shown
      clinical effects in the treatment of rheumatoid arthritis. JAKs are important
      kinases in lymphocyte differentiation; however, their function in dendritic cells
      (DCs) is unknown. In this study, the function of JAKs in DCs was investigated
      with tofacitinib. METHODS: The effects of tofacitinib on the maturation of human
      monocyte-derived DCs induced by lipopolysaccharide (LPS) stimulation were
      investigated. In addition, its effects on T cell stimulatory capability was
      investigated by coculturing with naive CD45RA-positive T cells. RESULTS:
      Tofacitinib decreased expression of CD80/CD86 in a concentration-dependent manner
      in LPS-stimulated DCs; however, it did not affect HLA-DR expression. Tofacitinib
      suppressed tumour necrosis factor, interleukin (IL)-6 and IL-1beta production
      without affecting transforming growth factor (TGF)-beta and IL-10 production.
      Meanwhile, CD80/CD86 expression in DCs was enhanced by type I interferon (IFN)
      stimulation, and the LPS-induced CD80/CD86 expression was inhibited by an
      antibody to type I IFN receptor. Furthermore, tofacitinib suppressed production
      of type I IFN and activation of interferon regulatory factor (IRF)-7, which is a
      transcription factor involved in CD80/CD86 and type I IFN expression. Tofacitinib
      also decreased the T cell stimulatory capability of DCs and increased expression
      of indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2. CONCLUSIONS: Tofacitinib, a
      JAK1/JAK3 inhibitor, affected the activities of human DCs. It decreased CD80/CD86
      expression and T cell stimulatory capability through suppression of type I IFN
      signalling. These results suggest a novel mode of action for tofacitinib and a
      pivotal role for JAKs in the differentiation of DCs.

PMID- 24013647
TI  - Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis
      including ankylosing spondylitis: 24-week results of a double-blind randomised
      placebo-controlled Phase 3 study.
AB  - OBJECTIVES: To evaluate the efficacy and safety of certolizumab pegol (CZP) after
      24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with
      axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis
      (AS) and non-radiographic axSpA (nr-axSpA). METHODS: Patients with active axSpA
      were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg
      every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was
      ASAS20 (Assessment of SpondyloArthritis international Society 20) response at
      week 12. Secondary outcomes included change from baseline in Bath Ankylosing
      Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease
      Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI)
      linear. RESULTS: Baseline disease activity was similar between AS and nr-axSpA.
      At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and
      CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p<=0.004). At week 24,
      combined CZP arms showed significant (p<0.001) differences in change from
      baseline versus placebo in BASFI (-2.28 vs -0.40), BASDAI (-3.05 vs -1.05), and
      BASMI (-0.52 vs -0.07). Improvements were observed as early as week 1. Similar
      improvements were reported with CZP versus placebo in both AS and nr-axSpA
      subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious
      adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or
      malignancies were reported. CONCLUSIONS: CZP rapidly reduced the signs and
      symptoms of axSpA, with no new safety signals observed compared to the safety
      profile of CZP in RA. Similar improvements were observed across CZP dosing
      regimens, and in AS and nr-axSpA patients.

PMID- 24013649
TI  - The cell block technique revisited for cells cultured in adherence and as
      "spheres".
AB  - A simple modification of the cell block technique for cultured cells grown in
      different conditions and suitable for the construction of tissue micro arrays
      (TMA) is described. The application of mechanical stirring during clot formation
      allows the uniform dispersion of cells in the fibrin mesh, thus increasing the
      final volume of the embedded material of evenly distributed cells. This technique
      is easily applied to spheres-obtained from cell lines cultured under appropriate
      conditions-that are enriched in stem cells. The possibility of constructing TMA
      using cell lines (grown in adherence and as spheres) and samples of the
      corresponding tumors or normal tissues may allow the direct comparison of
      original tumors with in vitro-expanded cell lines. 

PMID- 24013648
TI  - Molecular composition and ultrastructure of the caveolar coat complex.
AB  - Caveolae are an abundant feature of the plasma membrane of many mammalian cell
      types, and have key roles in mechano-transduction, metabolic regulation, and
      vascular permeability. Caveolin and cavin proteins, as well as EHD2 and pacsin 2,
      are all present in caveolae. How these proteins assemble to form a protein
      interaction network for caveolar morphogenesis is not known. Using in vivo
      crosslinking, velocity gradient centrifugation, immuno-isolation, and tandem mass
      spectrometry, we determine that cavins and caveolins assemble into a homogenous
      80S complex, which we term the caveolar coat complex. There are no further
      abundant components within this complex, and the complex excludes EHD2 and pacsin
      2. Cavin 1 forms trimers and interacts with caveolin 1 with a molar ratio of
      about 1?4. Cavins 2 and 3 compete for binding sites within the overall coat
      complex, and form distinct subcomplexes with cavin 1. The core interactions
      between caveolin 1 and cavin 1 are independent of cavin 2, cavin 3, and EHD2
      expression, and the cavins themselves can still interact in the absence of
      caveolin 1. Using immuno-electron microscopy as well as a recently developed
      protein tag for electron microscopy (MiniSOG), we demonstrate that caveolar coat
      complexes form a distinct coat all around the caveolar bulb. In contrast, and
      consistent with our biochemical data, EHD2 defines a different domain at the
      caveolar neck. 3D electron tomograms of the caveolar coat, labeled using cavin
      MiniSOG, show that the caveolar coat is composed of repeating units of a unitary
      caveolar coat complex.

PMID- 24013650
TI  - Simple continuous-flow synthesis of Cu-In-Zn-S/ZnS and Ag-In-Zn-S/ZnS core/shell
      quantum dots.
AB  - We present a simple continuous-flow reaction for the synthesis of quaternary Cu
      In-Zn-S/ZnS and Ag-In-Zn-S/ZnS core/shell quantum dots (QDs) using inexpensive
      and low-toxic precursors. The composition and band gap of Cu-In-Zn-S and Ag-In-Zn
      S QDs were well controlled by changing the molar ratios of the starting
      materials. The PL quantum yields of Cu-In-Zn-S/ZnS core/shell quantum dots can
      reach as high as 40%. 

PMID- 24013652
TI  - Chemical bonding involving d-orbitals.
AB  - The landmark 1954 J. Chem. Soc. paper by Craig et al. exploring the role of d
      orbitals in chemical bonding is discussed. This paper set the agenda for
      discussions that continue until the present about topics in inorganic chemistry
      such as hypervalency, arguably the most significant bonding phenomenon to
      differentiate the chemistry of the 2p main group elements from their heavier
      congeners. 

PMID- 24013651
TI  - Structural and functional measures of efficacy in response to bevacizumab
      monotherapy in diabetic macular oedema: exploratory analyses of the BOLT study
      (report 4).
AB  - BACKGROUND: To describe structural and functional changes associated with
      diabetic macular oedema (DMO) treated with intravitreal bevacizumab over 24
      months. METHODS: A post-hoc analysis of the data of 34 patients that completed 24
      months follow-up in the intravitreal bevacizumab arm of a prospective, randomized
      controlled trial (BOLT study) was performed. The outcome measures previously used
      in clinical trials of intravitreal ranibizumab in DMO were employed to describe
      the visual acuity and macular thickness changes at 12 and 24 months. RESULTS: The
      standard outcomes of mean change in best corrected visual acuity (BCVA) and
      central macular thickness (CMT) in participants treated with bevacizumab were
      comparable to those reported in association with ranibizumab. However,
      exploratory analyses showed that thick maculae at baseline defined as CMT of >=
      400 um, remained significantly thicker than those <400 um with intensive
      bevacizumab therapy, despite a comparable gain in visual acuity at both 12 and 24
      months. The proportion of subjects that attained a dry macula doubled in both CMT
      groups between the 12 and 24-month time-points. CONCLUSIONS: These findings
      provide valuable information both for clinical practice and trials. Further
      studies are required to investigate the impact of intravitreal bevacizumab on
      retinal thickness profiles in DMO.

PMID- 24013653
TI  - [Informed consent consultation as a part of patient safety in pediatric
      traumatology].
AB  - In pediatric traumatology as in any other surgical specialty, every treatment
      measure has to be protected by an adequate clarification. A legally effective
      clarification has to cover various aspects, such as diagnosis, treatment, risk
      and safety clarification and leads to an informed consent consultation. The
      contents of this informed consent discussion must be documented. The nature and
      extent of clarification, among other things depend on the urgency of the
      procedure and in an emergency it can be dispensed with in pediatric traumatology.
      In the case of minors the conversation must be conducted basically in the
      presence of both parents as they alone are legally entitled to give approval.
      General treatment proxies are not allowed. If it is not possible to talk to both
      parents the physician is allowed to trust that the parent present represents the
      will of the absent parent. Intervention cannot be carried out against the will of
      adolescents capable of self-determination even with the consent of the parents.
      The application of these rules is illustrated by means of practical examples.

PMID- 24013654
TI  - Effects of mosapride on esophageal motor activity and esophagogastric junction
      compliance in healthy volunteers.
AB  - BACKGROUND: The effects of the prokinetic drug mosapride on esophageal motor
      activity vary at standard doses. In addition to esophageal motor activities,
      compliance of the esophagogastric junction (EGJ) is important for prevention of
      gastroesophageal reflux. However, the effects of mosapride on EGJ compliance have
      not been reported. Here, we investigated the effects of high-dose mosapride on
      esophageal motor activities and EGJ compliance. METHODS: Nine healthy volunteers
      were enrolled in the study. Peristaltic esophageal contraction and lower
      esophageal sphincter pressures before and after administration of 40 mg mosapride
      were examined by high resolution esophageal manometry. Esophageal compliance was
      also investigated by intra-esophageal impedance planimetry (EndoFLIP((r))).
      RESULTS: High-dose mosapride augmented peristaltic contractions, especially in
      the distal esophageal segments (P < 0.05). The mean resting lower esophageal
      sphincter pressure was elevated from 25.0 mmHg before administration to 28.9 mmHg
      after (P < 0.05). In addition, mosapride significantly reduced EGJ compliance (P
      < 0.05). CONCLUSIONS: Mosapride at 40 mg augmented esophageal motor activities
      and reduced EGJ compliance in healthy volunteers.

PMID- 24013656
TI  - The link between workforce health and safety and the health of the bottom line:
      tracking market performance of companies that nurture a "culture of health".
AB  - OBJECTIVE: To test the hypothesis that comprehensive efforts to reduce a
      workforce's health and safety risks can be associated with a company's stock
      market performance. METHODS: Stock market performance of Corporate Health
      Achievement Award winners was tracked under four different scenarios using
      simulation and past market performance. RESULTS: A portfolio of companies
      recognized as award winning for their approach to the health and safety of their
      workforce outperformed the market. Evidence seems to support that building
      cultures of health and safety provides a competitive advantage in the
      marketplace. This research may have also identified an association between
      companies that focus on health and safety and companies that manage other aspects
      of their business equally well. CONCLUSIONS: Companies that build a culture of
      health by focusing on the well-being and safety of their workforce yield greater
      value for their investors.

PMID- 24013655
TI  - The antihelmintic drug pyrvinium pamoate targets aggressive breast cancer.
AB  - WNT signaling plays a key role in the self-renewal of tumor initiation cells
      (TICs). In this study, we used pyrvinium pamoate (PP), an FDA-approved
      antihelmintic drug that inhibits WNT signaling, to test whether pharmacologic
      inhibition of WNT signaling can specifically target TICs of aggressive breast
      cancer cells. SUM-149, an inflammatory breast cancer cell line, and SUM-159, a
      metaplastic basal-type breast cancer cell line, were used in these studies. We
      found that PP inhibited primary and secondary mammosphere formation of cancer
      cells at nanomolar concentrations, at least 10 times less than the dose needed to
      have a toxic effect on cancer cells. A comparable mammosphere formation IC50 dose
      to that observed in cancer cell lines was obtained using malignant pleural
      effusion samples from patients with IBC. A decrease in activity of the TIC
      surrogate aldehyde dehydrogenase was observed in PP-treated cells, and inhibition
      of WNT signaling by PP was associated with down-regulation of a panel of markers
      associated with epithelial-mesenchymal transition. In vivo, intratumoral
      injection was associated with tumor necrosis, and intraperitoneal injection into
      mice with tumor xenografts caused significant tumor growth delay and a trend
      toward decreased lung metastasis. In in vitro mammosphere-based and monolayer
      based clonogenic assays, we found that PP radiosensitized cells in monolayer
      culture but not mammosphere culture. These findings suggest WNT signaling
      inhibition may be a feasible strategy for targeting aggressive breast cancer.
      Investigation and modification of the bioavailability and toxicity profile of
      systemic PP are warranted. 

PMID- 24013657
TI  - Working conditions and depressive symptoms: a prospective study of US adults.
AB  - OBJECTIVE: Prior longitudinal studies of negative working conditions and
      depression generally have used a single exposure indicator, such as job strain,
      and have required consistent availability of the measure across waves and
      selection of only those working at all measurement points. METHODS: Up to four
      waves of the Americans' Changing Lives study (1986 to 2001/2) and item-response
      theory (IRT) models were used to generate wave-specific measures of negative
      working conditions. Random-intercept linear mixed models assessed the association
      between the score and depressive symptoms. RESULTS: Adjusting for covariates,
      negative working conditions were associated with significantly greater depressive
      symptoms. CONCLUSIONS: A summary score of negative working conditions allowed the
      use of all available working conditions measures and predicted depressive
      symptoms in a nationally representative sample of US workers observed for up to
      15 years. Linear mixed models also allowed retention of intermittent workers.

PMID- 24013658
TI  - Pertussis vaccination of health care workers: ACOEM medical center occupational
      health section task force on pertussis vaccination of health care workers.

PMID- 24013661
TI  - High prevalence of oncogenic MYD88 and CD79B mutations in diffuse large B-cell
      lymphomas presenting at immune-privileged sites.
AB  - Activating mutations in CD79 and MYD88 have recently been found in a subset of
      diffuse large B-cell lymphoma (DLBCL), identifying B-cell receptor and MYD88
      signalling as potential therapeutic targets for personalized treatment. Here, we
      report the prevalence of CD79B and MYD88 mutations and their relation to
      established clinical, phenotypic and molecular parameters in a large panel of
      DLBCLs. We show that these mutations often coexist and demonstrate that their
      presence is almost mutually exclusive with translocations of BCL2, BCL6 and cMYC,
      or Epstein-Bar virus infection. Intriguingly, MYD88 mutations were by far most
      prevalent in immune-privileged site-associated DLBCL (IP-DLBCL), presenting in
      central nervous system (75%) or testis (71%) and relatively uncommon in nodal
      (17%) and gastrointestinal tract lymphomas (11%). Our results suggest that MYD88
      and CD79B mutations are important drivers of IP-DLBCLs and endow lymphoma
      initiating cells with tissue-specific homing properties or a growth advantage in
      these barrier-protected tissues. 

PMID- 24013662
TI  - A novel selective small-molecule PI3K inhibitor is effective against human
      multiple myeloma in vitro and in vivo.
AB  - Developing effective therapies against multiple myeloma (MM) is an unresolved
      challenge. Phosphatidylinositol-3-kinase (PI3K) activation may be associated with
      tumor progression and drug resistance, and inhibiting PI3K can induce apoptosis
      in MM cells. Thus, targeting of PI3K is predicted to increase the susceptibility
      of MM to anticancer therapy. The lead compound of a novel class of PI3K
      inhibitors, BAY80-6946 (IC50=0.5 nM against PI3K-alpha), was highly efficacious
      in four different MM cell lines, where it induced significant antitumoral effects
      in a dose-dependent manner. The compound inhibited cell cycle progression and
      increased apoptosis (P<0.001 compared with controls). Moreover, it abrogated the
      stimulation conferred by insulin-like growth-factor-1, a mechanism relevant for
      MM progression. These cellular effects were paralleled by decreased Akt
      phosphorylation, the main downstream target of PI3K. Likewise, profound
      antitumoral activity was observed ex vivo, as BAY80-6946 significantly inhibited
      proliferation of freshly isolated myeloma cells from three patients (P<0.001
      compared with vehicle). In addition, BAY80-6946 showed convincing in vivo
      activity against the human AMO-1 and MOLP-8 myeloma cell lines in a preclinical
      murine xenograft model, where treatment with 6 mg/kg every other day for 2 weeks
      reduced the cell numbers by 87.0% and 69.3%, respectively (P<0.001 compared with
      vehicle), without overt toxicity in treated animals. 

PMID- 24013663
TI  - Activation of Jak2 in patients with blast crisis chronic myelogenous leukemia:
      inhibition of Jak2 inactivates Lyn kinase.

PMID- 24013664
TI  - Pomalidomide: the new immunomodulatory agent for the treatment of multiple
      myeloma.
AB  - In this report, we provide a comprehensive review on the preclinical and clinical
      investigations conducted in development of the next-generation immunomodulatory
      drug (IMiD) pomalidomide for the treatment of relapsed/refractory multiple
      myeloma (MM). We consulted PubMed, MEDLINE, ASH, ASCO annual symposium abstracts
      and http://clinicaltrials.gov/ for the purpose of this literature review. Twenty
      six preclinical and 11 clinical studies were examined. These studies delineate
      the mechanisms of action of pomalidomide and attest to the robust clinical
      activity in relapsed/refractory MM. MM is the second most common hematological
      malignancy in the US. Despite availability of several therapeutic agents, MM
      remains incurable. Thus, the development of new therapies remains a priority.
      Pomalidomide is the newest member of the IMiDs class of drugs, and in preclinical
      and clinical investigations, it has demonstrated an improved efficacy and
      toxicity profile in comparison to its sister compounds, lenalidomide and
      thalidomide. Importantly, recent clinical studies have demonstrated its activity
      in relapsed or refractory myeloma, particularly in lenalidomide and bortezomib
      refractory patients. Thus, the addition of pomalidomide to the anti-myeloma
      armamentarium is widely anticipated to have a significant impact on the overall
      clinical outcome of advanced stage relapsed and refractory MM patients. 

PMID- 24013665
TI  - PKR negatively regulates leukemia progression in association with PP2A
      activation, Bcl-2 inhibition and increased apoptosis.
AB  - Reduced expression and activity of the proapoptotic, double-stranded RNA
      dependent protein kinase, PKR (protein kinase R) is observed in breast, lung and
      various leukemias, suggesting that loss of PKR potentiates transformation. Now we
      report that decreased PKR activity inhibits chemotherapy-induced apoptosis of
      leukemia cells both in vitro and in vivo. Inhibition of PKR expression or
      activity reduces protein phosphatase 2A (PP2A) activity, a B-cell lymphoma 2 (Bcl
      2) phosphatase, resulting in enhanced Bcl-2 phosphorylation. Thus, inhibition of
      PKR activity leads to hyperphosphorylation of Bcl-2, stabilization of Bcl-2/Bax
      interaction and decreased Bax insertion into the outer mitochondrial membrane.
      Treatment with the PP2A activator, FTY720, restores Bcl-2 dephosphorylation and
      apoptosis in cells with reduced PKR expression following stress. Significantly,
      xenografts of REH leukemic cells with reduced PKR display significantly increased
      tumor volume, increased resistance to doxorubicin treatment and shorter survival.
      Importantly, FTY720 treatment restores sensitivity to chemotherapy and prolongs
      overall survival of these mice. Collectively, these findings suggest that PP2A
      activation is a downstream target of PKR and the PKR/PP2A signaling axis is
      required for rapid and potent stress-induced apoptosis. Importantly, loss of PKR
      promotes leukemia progression and may serve as a biomarker for predicting
      chemosensitivity. 

PMID- 24013666
TI  - Induction of high-titer IgG antibodies against multiple leukemia-associated
      antigens in CML patients with clinical responses to K562/GVAX immunotherapy.
AB  - The ability to target myeloid leukemia with immunotherapy would represent a
      significant therapeutic advance. We report here immunological analysis of
      clinical trials of primary and secondary vaccination with K562/GM-CSF
      immunotherapy in adult chronic phase chronic myeloid leukemia patients (CML-CP)
      with suboptimal responses to imatinib mesylate. Using serological analysis of
      recombinant cDNA expression libraries of K562 with autologous vaccinated patient
      serum, we have identified 12 novel chronic myeloid leukemia-associated antigens
      (LAAs). We show that clinical responses following K562/GM-CSF vaccination are
      associated with induction of high-titer antibody responses to multiple LAAs. We
      observe markedly discordant patterns of baseline and induced antibody responses
      in these identically vaccinated patients. No single antigen was recognized in all
      responses to vaccination. We demonstrate that an additional 'booster' vaccination
      series can be given safely to those with inadequate responses to initial
      vaccination, and is associated with more frequent induction of IgG responses to
      antigens overexpressed in K562 vaccine compared with primary CML-CP. Finally,
      those with induced immune responses to the same LAAs often shared HLA subtypes
      and patients with clinical responses following vaccination recognized a partially
      shared but non-identical spectrum of antigens; both findings have potentially
      significant implications for cancer vaccine immunotherapy. 

PMID- 24013667
TI  - Post-column labeling techniques in amino acid analysis by liquid chromatography.
AB  - Amino acid analysis (AAA) has always presented an analytical challenge in terms
      of sample preparation, separation, and detection. Because of the vast number of
      amino acids, various separation methods have been applied taking into
      consideration the large differences in their chemical structures, which span from
      nonpolar to highly polar side chains. Numerous separation methods have been
      developed in the past 60 years, and impressive achievements have been made in the
      fields of separation, derivatization, and detection of amino acids (AAs). Among
      the separation methods, liquid chromatography (LC) prevailed in the AAA field
      using either pre-column or post-column labeling techniques in order to improve
      either separation of AAs or selectivity and sensitivity of AAA. Of the two
      approaches, the post-column technique is a more rugged and reproducible method
      and provides excellent AAs separation relatively free from interferences. This
      review considers current separations combined with post-column labeling
      techniques for AAA, comparison with the pre-column methods, and the strategies
      used to develop effective post-column methodology. The focus of the article is on
      LC methods coupled with post-column labeling techniques and studying the
      reactions to achieve optimum post-column derivatization (PCD) conditions in order
      to increase sensitivity and selectivity using various types of detectors (UV-Vis,
      fluorescence, electrochemical etc.) and illustrating the versatility of the PCD
      methods for practical analysis.

PMID- 24013669
TI  - Omega-3: a double-edged sword for autoimmune diseases.

PMID- 24013668
TI  - Selective regulation of lymphopoiesis and leukemogenesis by individual zinc
      fingers of Ikaros.
AB  - C2H2 zinc fingers are found in several key transcriptional regulators in the
      immune system. However, these proteins usually contain more fingers than are
      needed for sequence-specific DNA binding, which suggests that different fingers
      regulate different genes and functions. Here we found that mice lacking finger 1
      or finger 4 of Ikaros exhibited distinct subsets of the hematological defects of
      Ikaros-null mice. Most notably, the two fingers controlled different stages of
      lymphopoiesis, and finger 4 was selectively required for tumor suppression. The
      distinct defects support the hypothesis that only a small number of genes that
      are targets of Ikaros are critical for each of its biological functions. The
      subcategorization of functions and target genes by mutagenesis of individual zinc
      fingers will facilitate efforts to understand how zinc-finger transcription
      factors regulate development, immunity and disease. 

PMID- 24013670
TI  - A meta-analysis of the association of IL-6 -174 G/C and -572 G/C polymorphisms
      with systemic lupus erythematosus risk.
AB  - The results from previous studies on association of IL-6 -174 G/C and -572 G/C
      polymorphisms with the risk of systemic lupus erythematosus (SLE) remained
      inconsistent. Therefore, a meta-analysis was performed to assess the association
      between these two polymorphisms and SLE susceptibility. A literature-based search
      was conducted to identify all relevant studies. Pooled data were estimated by
      fixed- and random-effects models when appropriate. Nine publications were
      included in the meta-analysis, seven for -174 G/C polymorphism and three for -572
      G/C polymorphism. The results indicated that IL-6 -174 G/C polymorphism was
      significantly associated with SLE risk for recessive model and allele analysis in
      overall populations (OR 1.64, 95 % CI 1.10-2.45, P = 0.016; and 1.34, 1.05-1.72,
      P = 0.019, respectively, for recessive model and allele analysis) or in
      Caucasians (OR 1.37, 95 % CI 1.04-1.82, P = 0.027; and 1.27, 1.04-1.54, P =
      0.018, respectively, for recessive model and allele analysis). Also, significant
      association between IL-6 -572 G/C polymorphism and SLE was found under recessive
      model (OR 1.49, 95 % CI 1.10-2.01, P = 0.009), but not under dominant model and
      allele analysis (OR 1.05, 95 % CI 0.77-1.43, P = 0.750; and 1.21, 1.00-1.48, P =
      0.054, respectively, for dominant model and allele analysis). Additionally, our
      meta-analysis showed that IL-6 -174 G/C polymorphism was significantly associated
      with discoid skin lesions (P < 0.05). The present study indicates that IL-6 -174
      G/C and -572 G/C polymorphisms could be candidates for susceptibility to SLE.
      Furthermore, a large number of studies should be performed to explore the
      association of IL-6 polymorphisms with the risk and clinical characteristics of
      SLE patients in different ethnics. 

PMID- 24013671
TI  - Surface activation of graphene oxide nanosheets by ultraviolet irradiation for
      highly efficient anti-bacterials.
AB  - A comprehensive investigation of anti-bacterial properties of graphene oxide (GO)
      and ultraviolet (UV) irradiated GO nanosheets was carried out. Microscopic
      characterization revealed that the GO nanosheet-like structures had wavy features
      and wrinkles or thin grooves. Fundamental surface chemical states of GO
      nanosheets (before and after UV irradiation) were investigated using x-ray
      photoelectron spectroscopy and ultraviolet photoelectron spectroscopy. Minimum
      inhibitory concentration (MIC) results revealed that UV irradiated GO nanosheets
      have more pronounced anti-bacterial behavior than GO nanosheets and standard
      antibiotic, kanamycin. The MIC of UV irradiated GO nanosheets was 0.125 MUg ml-1
      for Escherichia coli and Salmonella typhimurium, 0.25 MUg ml-1 for Bacillus
      subtilis and 0.5 MUg ml-1 for Enterococcus faecalis, ensuring its potential as an
      anti-infective agent for controlling the growth of pathogenic bacteria. The
      minimum bactericidal concentration of normal GO nanosheets was determined to be
      two-fold higher than its corresponding MIC value, indicating promising
      bactericidal activity. The mechanism of anti-bacterial action was evaluated by
      measuring the enzymatic activity of beta-D-galactosidase for the hydrolysis of o
      nitrophenol-beta-D-galactopyranoside.

PMID- 24013672
TI  - Age determines the magnitudes of angiotensin II-induced contractions, mRNA, and
      protein expression of angiotensin type 1 receptors in rat carotid arteries.
AB  - In this study, we hypothesized that aging alters angiotensin II (Ang II)-induced
      vasomotor responses and expression of vascular mRNA and protein angiotensin type
      1 receptor (AT1R). Thus, carotid arteries were isolated from the following age
      groups of rats: 8 days, 2-9 months, 12-20 months, and 20-30 months, and their
      vasomotor responses were measured in a myograph after repeated administrations of
      Ang II. Vascular relative AT1R mRNA level was determined by quantitative reverse
      transcriptase polymerase chain reaction and the AT1R protein density was measured
      by Western blot. Contractions to the first administration of Ang II increased
      from 8 days to 6 months and then they decreased to 30 months. In general, second
      administration of Ang II elicited reduced contractions, but they also increased
      from 8 days until 2 months and then they decreased to 30 months. Similarly the
      AT1R mRNA level increased from 8 days to 12 months and then decreased to 30
      months. Similarly the AT1R protein density increased from 8 days until 16 months
      and then they decreased to 30 months. The pattern of these changes correlated
      with functional vasomotor data. We conclude that aging (newborn to senescence)
      has substantial effects on Ang II-induced vasomotor responses and AT1R signaling
      suggesting the importance of genetic programs. 

PMID- 24013673
TI  - Transition to sarcopenia and determinants of transitions in older adults: a
      population-based study.
AB  - BACKGROUND: Diagnostic criteria for sarcopenia from appendicular lean mass (ALM),
      strength, and performance have been proposed, but little is known regarding the
      progression of sarcopenia. We examined the time course of sarcopenia and
      determinants of transitioning toward and away from sarcopenia. METHODS: ALM, gait
      speed, and grip strength were assessed seven times over 9 years in 2,928
      initially well-functioning adults aged 70-79. Low ALM was defined as less than
      7.95 kg/m(2) (men) or less than 6.24 kg/m(2) (women), low performance as gait
      speed less than 1.0 m/s, low strength as grip strength less than 30 kg (men) or
      less than 20 kg (women). Presarcopenia was defined as low ALM and sarcopenia as
      low ALM with low performance or low strength. Hidden Markov modeling was used to
      characterize states of ALM, strength, and performance and model transitions
      leading to sarcopenia and death. Determinants of transitioning toward and away
      from sarcopenia were examined with logistic regression. RESULTS: Initially, 54%
      of participants had normal ALM, strength, and performance; 21% had presarcopenia;
      5% had sarcopenia; and 20% had intermediate characteristics. Of participants with
      normal ALM, strength, and performance, 1% transitioned to presarcopenia and none
      transitioned to sarcopenia. The greatest transition to sarcopenia (7%) was in
      presarcopenic individuals. Low-functioning and sarcopenia states were more likely
      to lead to death (12% and 13%). Higher body mass index (p < .001) and pain (p =
      .05) predicted transition toward sarcopenia, whereas moderate activity predicted
      transition from presarcopenia to more normal states (p = .02). CONCLUSIONS: Pain,
      physical activity, and body mass index, potentially modifiable factors, are
      determinants of transitions. Promotion of health approaching old age is important
      as few individuals transition away from their initial state.

PMID- 24013674
TI  - Exercise training modifies ghrelin and adiponectin concentrations and is related
      to inflammation in older adults.
AB  - The purpose of this study was to observe exercise training-induced effects on
      adiponectin, leptin, and ghrelin. Twenty-nine older, healthy participants were
      classified as physically active (comparison group: N = 15, 70.9 +/- 1.2 years) or
      physically inactive (exercise group: N = 14, 70.5 +/- 1.4 years). Exercise group
      participants completed 12 weeks of combined aerobic and resistance exercise
      training, whereas comparison group participants maintained their current level of
      exercise and served as a physically active comparison group. Monocyte phenotype,
      as well as serum ghrelin, leptin, adiponectin, and soluble tumor necrosis factor
      receptor II were analyzed prior to and following the 12-week period. Ghrelin and
      adiponectin increased 47% and 55%, respectively, in exercise group participants
      following exercise training. Percent change in ghrelin (post and pre) was
      negatively correlated with the percent change in CD14+CD16+ monocytes (post and
      pre) in exercise group participants. Despite no changes in body mass, these data
      contribute to evidence for the anti-inflammatory effects of exercise.

PMID- 24013675
TI  - Comparison of the effect of rose bengal- and eosin Y-mediated photodynamic
      inactivation on planktonic cells and biofilms of Candida albicans.
AB  - Candida albicans is an opportunistic yeast that can cause oral candidosis through
      the formation of a biofilm, an important virulence factor that compromises the
      action of antifungal agents. The objective of this study was to compare the
      effect of rose bengal (RB)- and eosin Y (EY)-mediated photodynamic inactivation
      (PDI) using a green light-emitting diode (LED; 532 +/- 10 nm) on planktonic cells
      and biofilms of C. albicans (ATCC 18804). Planktonic cultures were treated with
      photosensitizers at concentrations ranging from 0.78 to 400 MUM, and biofilms
      were treated with 200 MUM of photosensitizers. The number of colony-forming unit
      per milliliter (CFU/mL) was compared by analysis of variance and Tukey's test (P
      <= 0.05). After treatment, one biofilm specimen of the control and PDI groups
      were examined by scanning electron microscopy. The photosensitizers (6.25, 25,
      50, 200, and 400 MUM of EY, and 6.25 MUM of RB or higher) significantly reduced
      the number of CFU/mL in the PDI groups when compared to the control group. With
      respect to biofilm formation, RB- and EY-mediated PDI promoted reductions of 0.22
      log10 and 0.45 log10, respectively. Scanning electron microscopy showed that the
      two photosensitizers reduced fungal structures. In conclusion, EY- and RB
      mediated PDI using LED irradiation significantly reduced C. albicans planktonic
      cells and biofilms.

PMID- 24013676
TI  - Molecular structure and vibrational bands and 13C chemical shift assignments of
      both enmein-type diterpenoids by DFT study.
AB  - We report here theoretical and experimental studies on the molecular structure
      and vibrational and NMR spectra of both natural enmein type diterpenoids molecule
      (6, 7-seco-ent-kaurenes enmein type), isolated from the leaves of Isodon japonica
      (Burm.f.) Hara var. galaucocalyx (maxin) Hara. The optimized geometry, total
      energy, NMR chemical shifts and vibrational wavenumbers of epinodosinol and
      epinodosin have been determined using B3LYP method with 6-311G (d,p) basis set. A
      complete vibrational assignment is provided for the observed IR spectra of
      studied compounds. The calculated wavenumbers and 13C c.s. are in an excellent
      agreement with the experimental values. Quantum chemical calculations at the
      B3LYP/6-311G (d,p) level of theory have been carried out on studied compounds to
      obtain a set of molecular electronic properties (MEP,HOMO, LUMO and gap energies
      DeltaEg). Electrostatic potential surfaces have been mapped over the electron
      density isosurfaces to obtain information about the size, shape, charge density
      distribution and chemical reactivity of the molecules. 

PMID- 24013677
TI  - IBIL analysis of road dust samples from San Bernardo tunnel.
AB  - Road dust in urban or industrial sites is an important source of atmospheric
      particulate by re-suspension of finer particles that may contain potentially
      toxic pollutants. In this work Ion Beam Induced Luminescence (IBIL), Nuclear
      Magnetic Resonance and fluorescence spectroscopy analyses were used to
      characterize road dust samples with particle size lower than 250 MUm collected on
      the walls and on the floor of the ventilation air shaft of "Traforo del San
      Bernardo" highway tunnel. Moreover, for comparison, IBIL analyses were performed
      both on some possible anthropic sources of particulate matter and on a road dust
      reference sample (BCR-723). IBIL spectra as a function of the fluence were
      analyzed with a multivariate approach in order to identify the spectral
      components evolving with different rate. Nuclear Magnetic Resonance and
      fluorescence spectroscopy analyses were performed on extracted samples of the
      road dust in order to study the contribution of organic compounds to the IBIL
      features. Results point out that IBIL, here performed for the first time for road
      dust analysis, can be applied for the identification of compounds by
      characterizing the sample origin.

PMID- 24013678
TI  - Intramolecular resonance-assisted hydrogen bonds: a theoretical description by
      means of atomic charges and charge fluxes.
AB  - The characterization of intramolecular H-bonds in terms of atomic charges and
      charge fluxes (at the B3LYP/cc-pVTZ level of theory) has been extended to the
      case of the so called resonance-assisted (RA) H-bonds. A quadratic correlation
      between the charge fluxes phiH and the molecular IR absorption coefficients E
      that includes the entire family of the studied systems (31 of them) containing
      both intra- and intermolecular hydrogen bonds (O-H...O/N) confirmed the critical
      importance of the charge fluxes on the IR intensity enhancements. Since they
      reflect changing of the atomic charge distribution during the normal modes of
      vibrations, the dynamic nature of hydrogen bonding properties has been re
      emphasized. The changes of the charge flux of the hydroxyl hydrogen in an RA
      intramolecular H-bond are between those for "free" OH bonds and the values
      calculated for intermolecular H-bonds. The transition "free"->intramolecular
      >intermolecular is gradual and therefore the hydrogen charge flux can be
      considered as practically sufficient to give quantitative measure to the
      intuitively obvious statement that "intramolecular H-bonding is somehow in
      between no H-bonding situation and intermolecular H-bonding" and thus provide a
      quantitative and yet simple parameterization of H-bond strength. In strictly
      planar molecules, the difference of the sums of charges of atoms participating in
      the 6-membered H-bond ring DeltaSigma can serve as a measure of the charge
      delocalization after the H-bond is formed. The electronic charge is withdrawn
      from the group of six atoms when the H-bond is formed in nitrophenol (DeltaSigma=
      0.07), while the opposite is true (DeltaSigma=+0.03) for 2-hydroxy benzylidene
      amine. The corresponding values of the geometrical resonance parameter Delta are
      0.39 and 0.37, respectively, similar to those found for 2-hydroxy acetophenone
      and 2-hydroxy benzaldehyde. The extent of the pi-electron delocalization as
      measured by the resonance parameter Delta does not follow the strength of H-bond
      as measured by the charge flux phiH.

PMID- 24013680
TI  - Optimization of flow assisted entrapment of pollen grains in a microfluidic
      platform for tip growth analysis.
AB  - A biocompatible polydimethylsiloxane (PDMS) biomicrofluidic platform is designed,
      fabricated and tested to study protuberance growth of single plant cells in a
      micro-vitro environment. The design consists of an inlet to introduce the cell
      suspension into the chip, three outlets to conduct the medium or cells out of the
      chip, a main distribution chamber and eight microchannels connected to the main
      chamber to guide the growth of tip growing plant cells. The test cells used here
      were pollen grains which produce cylindrical protrusions called pollen tubes. The
      goal was to adjust the design of the microfluidic network with the aim to enhance
      the uniformly distributed positioning of pollen grains at the entrances of the
      microchannels and to provide identical fluid flow conditions for growing pollen
      tubes along each microchannel. Computational fluid analysis and experimental
      testing were carried out to estimate the trapping efficiencies of the different
      designs. 

PMID- 24013679
TI  - Stretch and activation of the human biarticular hamstrings across a range of
      running speeds.
AB  - PURPOSE: The human biarticular hamstrings [semimembranosus (SM), semitendinosus
      (ST) and biceps femoris long head (BF(LH))] have an important role in running.
      This study determined how hamstrings neuro-mechanical behaviour changed with
      faster running, and whether differences existed between SM, ST and BF(LH).
      METHODS: Whole-body kinematics and hamstrings electromyographic (EMG) activity
      were measured from seven participants running at four discrete speeds (range: 3.4
      +/- 0.1 to 9.0 +/- 0.7 m/s). Kinematic data were combined with a three
      dimensional musculoskeletal model to calculate muscle-tendon unit (MTU) stretch
      and velocity. Activation duration and magnitude were determined from EMG data.
      RESULTS: With faster running, MTU stretch and velocity patterns remained similar,
      but maxima and minima significantly increased. The hamstrings were activated from
      foot-strike until terminal stance or early swing, and then again from mid-swing
      until foot-strike. Activation duration was similar with faster running, whereas
      activation magnitude significantly increased. Hamstrings activation almost always
      ended before minimum MTU stretch, and it always started before maximum MTU
      stretch. Comparing the hamstrings, maximum MTU stretch was largest for BF(LH) and
      smallest for ST irrespective of running speed, while the opposite was true for
      peak-to-peak MTU stretch. Furthermore, peak MTU shortening velocity was largest
      for ST and smallest for BF(LH) at all running speeds. Finally, for the two
      fastest running speeds, the amount of MTU stretch that occurred during terminal
      swing after activation had started was less for BF(LH) compared to SM and ST.
      CONCLUSION: Differences were evident in biarticular hamstrings neuro-mechanical
      behaviour during running. Such findings have implications for hamstrings function
      and injury.

PMID- 24013681
TI  - Silver nanoprism enhanced fluorescence in YVO4:Eu3+ nanoparticles.
AB  - Silver nanoprisms of different sizes influence fluorescence enhancement in
      YVO4:Eu(3+) nanoparticles to various degrees under excitation of green light (532
      nm). The local field generated by silver nanoprisms and their dimers is simulated
      through the FDTD method and a direct correlation with fluorescence enhancement is
      established. 

PMID- 24013682
TI  - Conservative care in Europe--nephrologists' experience with the decision not to
      start renal replacement therapy.
AB  - BACKGROUND: For some patients with end-stage renal disease (ESRD), providing
      conservative care until death may be an acceptable alternative for renal
      replacement therapy (RRT). We aimed to estimate the occurrence of conservative
      care in Europe and evaluated opinions about which factors nephrologists consider
      important in their decision not to offer RRT. METHODS: With a web-based survey
      sent to nephrologists in 11 European countries, we inquired how often RRT was not
      started in 2009 and how specific factors would influence the nephrologists'
      decision to provide conservative care. We compared subgroups by nephrologist and
      facility characteristics using chi-square tests and Mann-Whitney U tests.
      RESULTS: We received 433 responses. Nephrologists decided to offer conservative
      care in 10% of their patients [interquartile range (IQR) 5-20%]. An additional 5%
      (IQR 2-10%) of the patients chose conservative care as they refused when
      nephrologists intended to start RRT. Patient preference (93%), severe clinical
      conditions (93%), vascular dementia (84%) and low physical functional status
      (75%) were considered extremely or quite important in the nephrologists' decision
      to provide conservative care. Nephrologists from countries with a low incidence
      of RRT, not-for-profit centres and public centres more often scored these factors
      as extremely or quite important than their counterparts from high-incidence
      countries, for-profit centres and private centres. CONCLUSIONS: Nephrologists
      estimated conservative care was provided to up to 15% of their patients in 2009.
      The presence of severe clinical conditions, vascular dementia and a low physical
      functional status are important factors in the decision-making not to start RRT.
      Patient preference was considered as a very important factor, confirming the
      importance of extensive patient education and shared decision-making.

PMID- 24013684
TI  - Is there an obesity-related epidemic of CKD starting already in childhood?

PMID- 24013683
TI  - Vitamin D receptor activation, left ventricular hypertrophy and myocardial
      fibrosis.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH), a common complication in chronic
      kidney disease (CKD), is associated with high cardiovascular mortality. The aim
      of this experimental study was to analyze the effect of different vitamin D
      receptor activators (VDRAs) on both LVH and myocardial fibrosis in chronic renal
      failure (CRF). METHODS: Male Wistar rats with CRF, carried out by 7/8
      nephrectomy, were treated intraperitoneally with equivalent doses of VDRAs
      (calcitriol, paricalcitol and alfacalcidol, 5 days per week) during 4 weeks. A
      placebo group (CRF + vehicle) and a Sham group with normal renal function served
      as controls. Biochemical, morphological, functional and molecular parameters
      associated with LVH were evaluated, as well as cardiac fibrosis, collagen I,
      transforming growth factor beta1 (TGFbeta1) and matrix metalloproteinase-1 (MMP1)
      expression. RESULTS: All VDRAs treatment prevented LVH, with values of
      cardiomyocyte size, LV wall and septum thickness and heart-body weight ratio
      similar to those observed in the Sham group. At molecular levels, all VDRAs
      attenuated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)
      expression compared with CRF + vehicle. The phosphorylation of ERK1/2, a signal
      for activating growth, was stimulated in the CRF + vehicle group; VDRAs use
      prevented this activation. Paricalcitol was the only VDRA used that maintained in
      the normal range all parameters associated with myocardial fibrosis (total
      collagen, collagen I, TGFbeta1 and MMP1). CONCLUSIONS: Our findings demonstrated
      that the three VDRAs used induced similar changes in bone metabolic parameters
      and LVH. In addition, paricalcitol was the only VDRA which showed a relevant
      beneficial effect in the reduction of myocardial fibrosis, a key factor in the
      myocardial dysfunction in CKD patients.

PMID- 24013685
TI  - Reduction and residual proteinuria are therapeutic targets in type 2 diabetes
      with overt nephropathy: a post hoc analysis (ORIENT-proteinuria).
AB  - BACKGROUND: Proteinuria is a major predictor for progression of renal disease,
      including diabetic nephropathy. In a post hoc analysis of the ORIENT, a double
      blinded randomized trial of 566 type 2 diabetic patients with nephropathy, we
      examined the risk association of composite renal outcome [end-stage renal
      disease, ESRD, doubling of serum creatinine (SCr) and death] with baseline,
      change and residual urinary protein/creatinine ratio (UPCR). METHODS: We
      estimated the hazard ratios (HRs) with 95% confidence interval (CI) of composite
      renal outcome with baseline UPCR (low <1.0 g/gCr; moderate >= 1.0 g/gCr, <3.0
      g/gCr and high >= 3.0 g/gCr) as well as percentage reduction of UPCR (Delta)
      (worsening: <0%; moderate: >= 0%, <30% and high >= 30%) and residual UPCR at 24
      weeks (remission <1.0 g/gCr; moderate >= 1.0 g/gCr, <3.0 g/gCr and heavy >= 3.0
      g/gCr). RESULTS: Compared with the low group with baseline UPCR < 1.0 g/gCr, the
      respective HRs with 95% CI in the moderate and high UPCR groups were 3.02 (1.76
      5.19) and 9.24 (5.43-15.73). Compared with patients with a worsening UPCR (<0%)
      at 24 weeks, the HR was 0.54 (0.39-0.74) in those with >= 0%, <30% DeltaUPCR and
      0.43 (0.31-0.61) in those with >= 30% DeltaUPCR. Compared with the remission at
      24 weeks, the HR was 2.12 (1.28-3.49) in moderate residual proteinuria and 4.59
      (2.74-7.69) in heavy residual proteinuria. Compared with patients with residual
      UPCR >= 1.0 g/gCr and DeltaUPCR <30%, the HR in those with DeltaUPCR >= 30% and
      residual UPCR<1.0 g/gCr was 0.38 (0.22-0.64). CONCLUSIONS: In patients with type
      2 diabetes and overt nephropathy, over 30% reduction of UPCR compared with
      baseline and/or residual UPCR<1.0 g/gCr at 24 weeks predicted renoprotection.
      These values may be used as targets to guide anti-proteinuric and renoprotective
      therapy in diabetic nephropathy. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00141453.

PMID- 24013688
TI  - [Abstracts of the 65th Congress of the German Society for Urology. September 25
      28, 2013. Dresden, Germany].

PMID- 24013686
TI  - Iron binding at specific sites within the octameric HbpS protects streptomycetes
      from iron-mediated oxidative stress.
AB  - The soil bacterium Streptomyces reticuli secretes the octameric protein HbpS that
      acts as a sensory component of the redox-signalling pathway HbpS-SenS-SenR. This
      system modulates a genetic response on iron- and haem-mediated oxidative stress.
      Moreover, HbpS alone provides this bacterium with a defence mechanism to the
      presence of high concentrations of iron ions and haem. While the protection
      against haem has been related to its haem-binding and haem-degrading activity,
      the interaction with iron has not been studied in detail. In this work, we
      biochemically analyzed the iron-binding activity of a set of generated HbpS
      mutant proteins and present evidence showing the involvement of one internal and
      two exposed D/EXXE motifs in binding of high quantities of ferrous iron, with the
      internal E78XXE81 displaying the tightest binding. We additionally show that HbpS
      is able to oxidize ferrous to ferric iron ions. Based on the crystal structure of
      both the wild-type and the mutant HbpS-D78XXD81, we conclude that the local
      arrangement of the side chains from the glutamates in E78XXE81 within the
      octameric assembly is a pre-requisite for interaction with iron. The data
      obtained led us to propose that the exposed and the internal motif build a highly
      specific route that is involved in the transport of high quantities of iron ions
      into the core of the HbpS octamer. Furthermore, physiological studies using
      Streptomyces transformants secreting either wild-type or HbpS mutant proteins and
      different redox-cycling compounds led us to conclude that the iron-sequestering
      activity of HbpS protects these soil bacteria from the hazardous side effects of
      peroxide- and iron-based oxidative stress. 

PMID- 24013689
TI  - Focus Group Evaluation of the LIVE Network-An Audio Music Program to Promote ART
      Adherence Self-Management.
AB  - We present the results of 3 focus groups conducted to assess the utility, appeal,
      and feasibility of the LIVE Network (LN), a 70-minute audio music program
      developed to educate and motivate HIV-infected persons to adhere to
      antiretroviral therapy (ART) and self-manage medication-related side effects.
      Participants included 15 African American, 2 caucasian, and 1 race unknown HIV
      infected persons who had been taking ART for at least 6 months. In general, the
      LN was well liked, relevant, educational, and motivational. It empowered and
      motivated participants to be responsible for their adherence self-care. One of
      the more surprising findings was how freely focus group participants shared the
      program with family and friends as a means of education and also as a means of
      disclosure. Moreover, the positive reception of the LN by individuals outside of
      the focus groups, especially children and adolescents, speaks well for the
      potential broad appeal of this type of program.

PMID- 24013690
TI  - Donor cell-derived leukemia after cord blood transplantation and a review of the
      literature: differences between cord blood and BM as the transplant source.
AB  - Donor cell-derived leukemia (DCL) is a rare complication of SCT. Here, we present
      a case of DCL following cord blood transplantation (CBT) and review the clinical
      features of previously reported DCL. To our knowledge, this is the first report
      comparing clinical characteristics of DCL from the standpoint of the transplant
      source, with umbilical cord blood and BM. AML and myelodysplastic syndrome (MDS)
      were recognized more frequently in DCL after CBT, whereas the incidence of AML
      and ALL was similar after BMT. The median duration between the occurrence of DCL
      following CBT and BMT was 14.5 and 36 months, respectively. DCL occurred in a
      significantly shorter period after CBT than after BMT. Abnormal karyotypes
      involving chromosome 7 were observed in 52.4% of CBT recipients and 17.3% of BMT
      recipients; this was a statistically significant difference. Particularly, the
      frequency of monosomy 7 was significantly higher in DCL after CBT than after BMT.
      The types of abnormal karyotypes in DCL following BMT were similar to those
      characteristically observed in adult de novo AML and MDS. DCL patients generally
      have a poor prognosis in both groups. SCT is the best treatment for curing DCL.
      DCL appears to have different clinical features according to the transplant
      source. 

PMID- 24013692
TI  - Plasticizer concentration in cord blood cryopreserved with DMSO.

PMID- 24013691
TI  - Expansion of donor-reactive host T cells in primary graft failure after
      allogeneic hematopoietic SCT following reduced-intensity conditioning.
AB  - Graft rejection remains a major obstacle in allogeneic hematopoietic SCT
      following reduced-intensity conditioning (RIC-SCT), particularly after cord blood
      transplantation (CBT). In a murine MHC-mismatched model of RIC-SCT, primary graft
      rejection was associated with activation and expansion of donor-reactive host T
      cells in peripheral blood and BM early after SCT. Donor-derived dendritic cells
      are at least partly involved in host T-cell activation. We then evaluated if such
      an expansion of host T cells could be associated with graft rejection after RIC
      CBT. Expansion of residual host lymphocytes was observed in 4/7 patients with
      graft rejection at 3 weeks after CBT, but in none of the 17 patients who achieved
      engraftment. These results suggest the crucial role of residual host T cells
      after RIC-SCT in graft rejection and expansion of host T cells could be a marker
      of graft rejection. Development of more efficient T cell-suppressive conditioning
      regimens may be necessary in the context of RIC-SCT. 

PMID- 24013693
TI  - Prolonged apnea, caused by remifentanil, during awakening from anesthesia for
      emergency ventriculoperitoneal shunt placement.

PMID- 24013694
TI  - Modeling charge recombination in dye-sensitized solar cells using first
      principles electron dynamics: effects of structural modification.
AB  - We have performed real-time excited state simulations of electron injection and
      charge recombination at a dye/semiconductor interface within the framework of
      time-dependent density functional theory (TDDFT). We found that by inserting a
      phenyl ring into the organic dye, the charge recombination rate is slowed down by
      about four times, while the injection rate keeps almost the same. This introduces
      a drastic increase in the energy conversion efficiency by several folds, in
      agreement with experimental observations. Quantum simulations thus provide a new
      way to understand the role of the dye's building blocks and offer new strategies
      to optimize individual energy transfer steps for improving the efficiency in
      renewable energy applications. 

PMID- 24013695
TI  - Chemical composition, techno-functional and sensory properties and effects of
      three dietary fibers on the quality characteristics of Tunisian beef sausage.
AB  - This study determined the effects of three dietary fibers namely, VITACEL LC200
      powdered cellulose (LC200), barley beta-glucan concentrate (BBC), and VITACEL
      KF500 potato fiber (KF500), on the techno-functional and sensory properties and
      quality characteristics of Tunisian beef sausage. The findings revealed
      interesting functional properties for LC200 fiber. This fiber displayed high
      water binding capacity (WBC) and oil binding capacity (OBC), values of 16.2 g/g
      and 10.2 g/g, respectively, which are higher than reported for most fruit and
      vegetable fiber concentrates. The application of LC200 improved the masticability
      and elasticity of beef sausage formulations and minimized their hardness and
      production costs without negatively affecting their sensory properties. Overall,
      the findings demonstrate the potential functional and economic utility of LC200
      fiber as a promising source of dietary fiber.

PMID- 24013696
TI  - Effects of kimchi and smoking on quality characteristics and shelf life of cooked
      sausages prepared with irradiated pork.
AB  - The combined effects of kimchi powder (KP) and smoking (SM) on the quality
      characteristics and shelf life of cooked sausage prepared with 10 kGy irradiated
      pork (IP) were studied. The cooked sausages were formulated with single or
      combined treatment of 0.5% KP and SM (70 degrees C for 30 min). IP+KP+SM
      treatment showed increased redness, hardness, gumminess, and chewiness, but
      decreased cooking yield. As for sensory evaluation, treatment with both KP and SM
      was effective to mask the radiolytic off-flavor. Moreover, the cooked sausage
      treated with both KP and SM had the highest color, flavor, and overall acceptance
      (P<0.05), where the differences of flavor patterns were verified by using an
      electronic nose. During chilled storage for 4 weeks, the combined treatment is
      effective to retard lipid oxidation, formation of volatile compound, and total
      microbial number due to the addition of KP. Therefore, usages of KP and SM can
      provide improved quality characteristics and shelf life of cooked sausage
      prepared with IP.

PMID- 24013697
TI  - Effect of sex and final fattening on ultrasound and carcass traits in Iberian
      pigs.
AB  - A hundred and twenty-five castrated Iberian pigs (61 males and 64 females, from
      106.9 kg of live weight at star to 160.3 kg at slaughter) was used to investigate
      the effect of feeding system on carcass attributes (backfat thickness and loin
      area measured with ultrasound before slaughter, and intramuscular fat and weights
      and yields of hams, forelegs and loins after slaughter). Pigs were fattened
      outdoor under extensive conditions. There were 4 treatments: "montanera", M;
      "recebo", R; "cebo a campo", C; and high oleic fed, O). Ultrasound images were
      collected at two rib locations (10th and 14th). M and O groups had the highest
      fat thickness and loin area was lower in M than in C group. M and O showed higher
      carcass weight and yield than the other groups. The largest ham weight was for C
      and the lowest for M groups. Loin weight and yield were higher in M and R than
      the other two groups (O and C).

PMID- 24013698
TI  - Influence of PA6 nanocomposite films on the stability of vacuum-aged beef loins
      during storage in modified atmospheres.
AB  - A masterbatch of polyamide 6 (PA6) containing dispersed nanoclays, was used to
      fabricate a novel multilayer film for vacuum packed meat. Performance of the
      nanocomposite was compared to a control PA6 multilayer and a high barrier
      commercial film. Addition of nanoclays improved oxygen barrier properties, UV
      blocking capability and stiffness. Beef loins were vacuum-aged using the three
      films for 0 7, 14 and 21 days at 2 degrees C. After each ageing time, beef steaks
      were packaged in commercial trays and high oxygen atmosphere and stored at 4
      degrees C for 9 days. Beef quality parameters and gas content were studied during
      display time in MAP (1, 3, 6 and 9 d). Beef quality parameters were not
      influenced by the packaging materials used during ageing and the performance of
      nanocomposites was comparable to high barrier films. Ageing had a positive impact
      on the stabilization of redness up to day 6 in MAP. Thereafter, oxymyoglobin
      content and oxidation levels were negatively influenced by ageing.

PMID- 24013699
TI  - Aitchbone hanging and ageing period are additive factors influencing pork eating
      quality.
AB  - The effects of abattoir, carcase weight (60 or 80 kg HCW), hanging method
      (Achilles or aitchbone) and ageing period (2 or 7 day post-slaughter) on eating
      quality attributes of pork were investigated in this 3*2*2*2 factorial study. A
      total of 144 Large White*Landrace female pigs were slaughtered at one of three
      abattoirs and sides hung from either the Achilles tendon or the aitchbone. After
      24 h chilling, loin (M. longissimus thoracis et lumborum) and topside (M.
      semimembranosus) muscles were individually vacuum packaged and aged for 2 or 7
      days post-slaughter. Consumers (n=852) evaluated eating quality. Neither abattoir
      nor carcase weight influenced tenderness, flavour or overall liking of pork.
      Improvements in tenderness, flavour and overall liking were found due to
      aitchbone hanging (P<0.001) and ageing (P<0.001) for 7 days compared with
      Achilles-hung carcases and pork aged for 2 days, respectively. This study
      demonstrated that aitchbone hanging and 7 day ageing can improve eating quality,
      but these effects were additive as the interaction term was not significant.

PMID- 24013700
TI  - Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV
      infected rhesus macaques.
AB  - The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) is of
      global concern: the virus has caused severe respiratory illness, with 111
      confirmed cases and 52 deaths at the time of this article's publication.
      Therapeutic interventions have not been evaluated in vivo; thus, patient
      management relies exclusively on supportive care, which, given the high case
      fatality rate, is not highly effective. The rhesus macaque is the only known
      model organism for MERS-CoV infection, developing an acute localized to
      widespread pneumonia with transient clinical disease that recapitulates mild to
      moderate human MERS-CoV cases. The combination of interferon-alpha2b and
      ribavirin was effective in reducing MERS-CoV replication in vitro; therefore, we
      initiated this treatment 8 h after inoculation of rhesus macaques. In contrast to
      untreated, infected macaques, treated animals did not develop breathing
      abnormalities and showed no or very mild radiographic evidence of pneumonia.
      Moreover, treated animals showed lower levels of systemic (serum) and local
      (lung) proinflammatory markers, in addition to fewer viral genome copies,
      distinct gene expression and less severe histopathological changes in the lungs.
      Taken together, these data suggest that treatment of MERS-CoV infected rhesus
      macaques with IFN-alpha2b and ribavirin reduces virus replication, moderates the
      host response and improves clinical outcome. As these two drugs are already used
      in combination in the clinic for other infections, IFN-alpha2b and ribavirin
      should be considered for the management of MERS-CoV cases. 

PMID- 24013701
TI  - Quantitative imaging of disease signatures through radioactive decay signal
      conversion.
AB  - In the era of personalized medicine, there is an urgent need for in vivo
      techniques able to sensitively detect and quantify molecular activities.
      Sensitive imaging of gamma rays is widely used; however, radioactive decay is a
      physical constant, and its signal is independent of biological interactions.
      Here, we introduce a framework of previously uncharacterized targeted and
      activatable probes that are excited by a nuclear decay-derived signal to identify
      and measure molecular signatures of disease. We accomplished this by using
      Cerenkov luminescence, the light produced by beta-particle-emitting radionuclides
      such as clinical positron emission tomography (PET) tracers. Disease markers were
      detected using nanoparticles to produce secondary Cerenkov-induced fluorescence.
      This approach reduces background signal compared to conventional fluorescence
      imaging. In addition to tumor identification from a conventional PET scan, we
      demonstrate the medical utility of our approach by quantitatively determining
      prognostically relevant enzymatic activity. This technique can be applied to
      monitor other markers and represents a shift toward activatable nuclear medicine
      agents. 

PMID- 24013702
TI  - Deep sedation during catheter ablation for atrial fibrillation in elderly
      patients.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF
      incidence increases with age. AF ablation procedures are routinely performed
      under deep sedation with propofol. The purpose of the study was to evaluate if
      propofol deep sedation during AF ablation is safe in elderly patients. METHODS:
      Four hundred one consecutive patients (mean age, 61.4 +/- 11.1 years; range, 20
      82; 66.3 % men) who were presented to our institution for ablation of symptomatic
      AF were enrolled. Patients were divided into three groups: Patients in group A
      were <=50 years old; patients in group B were 51-74 years old; and patients in
      group C were >=75 years old. Procedures were performed under deep sedation with
      propofol, midazolam, and piritramide. SaO2, electrocardiogram, arterial blood
      pressure, and arterial blood gas were monitored throughout the procedure.
      Sedation-related complications, intraprocedural complications, and other adverse
      events were evaluated. Fisher exact or chi (2) tests were used for comparison of
      adverse events and complications among groups. Analysis of variance was used to
      compare sedation- and procedure-related parameters. RESULTS: Fifty-three (13.2 %)
      elderly patients were in group C and were compared to 73 (18.2 %) patients in
      group A and 275 (68.8 %) in group B. No significant differences in sedation
      related or intraprocedural complications were seen (group A, 1.4 %; group B, 1.1
      %; group C, 3.7 %; p = 0.336). Despite a significantly greater drop in systolic
      blood pressure in under sedation in group C (group A, 15.5 +/- 9.5 mmHg; group B,
      18.9 +/- 16.3 mmHg; group C, 32.3 +/- 15.5 mmHg; p < 0.001), no prolonged
      hypotension was observed. The rate of other adverse events (delirium, respiratory
      infection, renal failure) was significantly higher in group C (9.4 %), compared
      to group A (0 %) and group B (2.2 %; p = 0.004). CONCLUSION: Deep sedation with
      propofol and midazolam during AF ablation did not result in an increased rate in
      sedation-related complications in elderly patients. Similarly, the rate of
      procedural complications was not significantly different among the study groups.
      The rate of respiratory infections and renal failure was significantly higher in
      the elderly. All adverse events were treated successfully without any remaining
      sequelae.

PMID- 24013703
TI  - Effectiveness of VF induction with DC fibber versus conventional induction
      methods in patients on chronic amiodarone therapy.
AB  - BACKGROUND: Amiodarone therapy, especially chronic, can result in difficult
      ventricular fibrillation (VF) inductions during implantable cardioverter
      defibrillator (ICD) testing. The efficacy of various VF induction methods on
      patients treated with amiodarone has not been well described. This prospective
      analysis evaluated the impact of direct current (DC) fibber, burst fibber, and
      synchronized T-wave shock VF induction methods. METHODS: Data were collected from
      one study and two enrolling centers totaling 14 ICD patients (92.9 % male, age
      64.3 years (range 23.6-81.2)). A minimum of two successful VF inductions from
      each patient were required to be included in the study analysis. Each VF
      induction method was attempted in each patient. Non-sustained VF resulting in an
      aborted shock was considered an induction failure. All 14 patients were on
      chronic amiodarone therapy. RESULTS: From a total of 42 attempted inductions, 25
      (59.5 %) were successful at inducing VF. The success rates of effective induction
      of VF during the first attempt using DC, burst, and Shock-on-T are 100, 50, and
      28.6 %, respectively. DC fibber had significantly higher VF induction rates than
      Shock-on-T (p = 0.004) or burst fibber (p = 0.02). There was no difference
      between Shock-on-T and burst fibber (p = 0.45). CONCLUSION: The success rate of
      VF induction using DC fibber method is significantly higher than either Shock-on
      T or burst fibber induction methods for patients on chronic amiodarone therapy.
      This may facilitate defibrillation threshold testing in such patients.

PMID- 24013704
TI  - Prospective evaluation of cinefluoroscopy and chest radiography for Riata lead
      defects: implications for future lead screening.
AB  - INTRODUCTION: Lead insulation defects with externalization of the conductors
      exist in Riata defibrillator leads. Cinefluoroscopy is currently the gold
      standard to detect such defects. Prospective evaluation of alternative screening
      options such as chest radiography (CXR), which has been recommended by the FDA,
      is not well described. METHODS AND RESULTS: Patients with Riata leads underwent
      cinefluoroscopy, CXR, and device interrogation. Leads were classified as abnormal
      (clear cable separation), borderline, or normal by independent evaluation of
      cinefluoroscopy and CXR. CXR evaluation was done in two ways as follows: (1)
      routine CXR read by daily staff radiologists for lead screening and (2) CXR
      evaluation by a radiologist educated about the lead defect. One hundred two
      patients were evaluated at our institution. Cinefluoroscopy showed externalized
      conductors in 33 patients (32 %). Twenty-five of 33 patients (76 %) who had
      abnormal cinefluoroscopic findings had abnormal CXR findings on blinded review by
      the educated radiologist. All 25 patients with abnormal CXR had abnormal findings
      on cinefluoroscopy. Daily staff radiologists without direct education other than
      prompts for lead screening detected CXR abnormalities in only 8 out of 102 (8 %)
      cases. CONCLUSION: Cinefluoroscopy appears to be more sensitive than CXR for the
      detection of Riata cable extrusion. Interpretation of CXR by a radiologist with
      education in lead defects correlates highly with cinefluoroscopy with very high
      specificity. Depending on available resources for screening, CXR may be a
      reasonable alternative to cinefluoroscopy. Multidisciplinary collaboration across
      specialties (radiology and electrophysiology) can lead to improved diagnostic
      capability and thus the potential for enhanced quality of care.

PMID- 24013705
TI  - Fragmented QRS as a predictor of arrhythmic events in patients with hypertrophic
      obstructive cardiomyopathy.
AB  - OBJECTIVES: This study aims to determine whether fragmented QRS (fQRS) in the
      surface electrocardiogram (ECG) at implantable cardioverter defibrillator (ICD)
      implant can predict arrhythmic events using appropriate therapy delivered by the
      ICD as a surrogate. BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) is
      a genetic disorder associated with life-threatening arrhythmias frequently
      requiring an ICD. Seeking a noninvasive method of risk stratification remains a
      challenge. METHODS: This paper is a retrospective, multicenter study of patients
      with HOCM and ICD. Surface 12-lead ECGs were analyzed. Appropriate therapy was
      validated by a blinded Core Lab. Univariate and multivariate analyses were
      performed. A p value of <0.05 was considered significant. RESULTS: We included
      102 patients from 13 centers. Mean age at implant was 41.16 +/- 18.25 years, 52%
      were male. Mean left ventricular ejection fraction was 61.56 +/- 9.46% and two
      thirds had heart failure according to the New York Heart Association class I.
      Secondary prophylaxis ICD implantation was the indication for implant in 40.2% of
      cases. About half received a single-chamber ICD. fQRS was present at the time of
      diagnosis in 21 and in 54% at ICD implant. At a mean follow-up of 47.8 +/- 39.3
      months, 41 patients (40.2%) presented with appropriate therapy. In a multivariate
      logistic regression, predictors of appropriate therapy included fQRS at implant
      (odds ratio [OR], 16.4; 95% confidence interval [CI], 3.6-74.0; p = 0.0003),
      history of combined ventricular tachycardia/fibrillation/sudden death (OR, 14.3;
      95% CI, 3.2-69.3; p = 0.001) and history of syncope (OR, 5.5; 95% CI, 1.5-20.4; p
      = 0.009). Ten deaths (9.8%) occurred during the follow-up. fQRS in the lateral
      location increased the risk of appropriate therapy (p < 0.0001). CONCLUSIONS:
      fQRS predicts arrhythmic events in patients with HOCM and should be considered in
      a model of risk stratification.

PMID- 24013706
TI  - The extraordinary evolutionary history of the reticuloendotheliosis viruses.
AB  - The reticuloendotheliosis viruses (REVs) comprise several closely related
      amphotropic retroviruses isolated from birds. These viruses exhibit several
      highly unusual characteristics that have not so far been adequately explained,
      including their extremely close relationship to mammalian retroviruses, and their
      presence as endogenous sequences within the genomes of certain large DNA viruses.
      We present evidence for an iatrogenic origin of REVs that accounts for these
      phenomena. Firstly, we identify endogenous retroviral fossils in mammalian
      genomes that share a unique recombinant structure with REVs-unequivocally
      demonstrating that REVs derive directly from mammalian retroviruses. Secondly,
      through sequencing of archived REV isolates, we confirm that contaminated
      Plasmodium lophurae stocks have been the source of multiple REV outbreaks in
      experimentally infected birds. Finally, we show that both phylogenetic and
      historical evidence support a scenario wherein REVs originated as mammalian
      retroviruses that were accidentally introduced into avian hosts in the late
      1930s, during experimental studies of P. lophurae, and subsequently integrated
      into the fowlpox virus (FWPV) and gallid herpesvirus type 2 (GHV-2) genomes,
      generating recombinant DNA viruses that now circulate in wild birds and poultry.
      Our findings provide a novel perspective on the origin and evolution of REV, and
      indicate that horizontal gene transfer between virus families can expand the
      impact of iatrogenic transmission events.

PMID- 24013707
TI  - Screening for sexual dysfunction in women diagnosed with breast cancer:
      systematic review and recommendations.
AB  - Breast cancer patients are at increased risk of sexual dysfunction. Despite this,
      both patients and practitioners are reluctant to initiate a conversation about
      sexuality. A sexual dysfunction screening tool would be helpful in clinical
      practice and research, however, no scale has yet been identified as a "gold
      standard" for this purpose. The present review aimed at evaluating the scales
      used in breast cancer research in respect to their psychometric properties and
      the extent to which they measure the DSM-5/ICD-10 aspects of sexual dysfunction.
      A comprehensive search of the literature was conducted for the period 1992-2013,
      yielding 129 studies using 30 different scales measuring sexual functioning, that
      were evaluated in the present review. Three scales (Arizona Sexual Experience
      Scale, Female Sexual Functioning Index, and Sexual Problems Scale) were
      identified as most closely meeting criteria for acceptable psychometric
      properties and incorporation of the DSM-5/ICD-10 areas of sexual dysfunction.
      Clinical implications for implementation of these measures are discussed as well
      as directions for further research. 

PMID- 24013708
TI  - Targeted elimination of breast cancer cells with low proteasome activity is
      sufficient for tumor regression.
AB  - Breast cancers are thought to be organized hierarchically with a small number of
      breast cancer stem cells (BCSCs), able to regrow a tumor after sublethal
      treatment while their progeny lack this feature. Furthermore, BCSCs are highly
      resistant to conventional anticancer treatments. According to the cancer stem
      cell hypothesis, all cancer stem cells in a tumor have to be eliminated to
      achieve cancer cure. In this study we tested if targeted elimination of BCSCs
      leads to tumor regression. Specific targeting of BCSCs was achieved via a unique
      imaging and targeting system that relies on their low proteasome activity. In our
      system breast cancer cells stably express a fluorescent fusion protein, thymidine
      kinase-ZsGreen-cODC, which is readily degraded after translation in cells with
      normal 26S proteasome activity. However, cells with low proteasome activity
      accumulate this fluorescent fusion protein, thus allowing for their
      identification, tracking, and specific elimination. Here, we show that the
      activity of the 26S proteasome was significantly down-regulated in MCF-7, T47D,
      and MDA-MB-231 cultures enriched for BCSCs. Treatment with ganciclovir resulted
      in abrogation of sphere formation in vitro, and tumor regression in vivo, thus
      demonstrating that targeted elimination of BCSCs leads to loss of self-renewal in
      vitro and tumor regression in vivo. We conclude that specific targeting of BCSCs
      could be a useful strategy to improve treatment outcome. 

PMID- 24013710
TI  - A non-covalent strategy to prepare electron donor-acceptor rotaxanes.
AB  - A straightforward non-covalent synthetic strategy for producing donor-acceptor
      rotaxanes is reported. Femtosecond absorption spectroscopy illustrates that the
      use of this strategy gives rise to supramolecular chromophores with different
      electron transfer behavior. 

PMID- 24013709
TI  - Timeliness vaccination of measles containing vaccine and barriers to vaccination
      among migrant children in East China.
AB  - BACKGROUND: The reported coverage rates of first and second doses of measles
      containing vaccine (MCV) are almost 95% in China, while measles cases are
      constantly being reported. This study evaluated the vaccine coverage, timeliness,
      and barriers to immunization of MCV1 and MCV2 in children aged from 8-48 months.
      METHODS: We assessed 718 children aged 8-48 months, of which 499 children aged 18
      48 months in September 2011. Face to face interviews were administered with
      children's mothers to estimate MCV1 and MCV2 coverage rate, its timeliness and
      barriers to vaccine uptake. RESULTS: The coverage rates were 76.9% for MCV1 and
      44.7% for MCV2 in average. Only 47.5% of surveyed children received the MCV1
      timely, which postpone vaccination by up to one month beyond the stipulated age
      of 8 months. Even if coverage thus improves with time, postponed vaccination adds
      to the pool of unprotected children in the population. Being unaware of the
      necessity for vaccination and its schedule, misunderstanding of side-effect of
      vaccine, and child being sick during the recommended vaccination period were
      significant preventive factors for both MCV1 and MCV2 vaccination. Having
      multiple children, mother's education level, household income and children with
      working mothers were significantly associated with delayed or missing MCV1
      immunization. CONCLUSIONS: To avoid future outbreaks, it is crucial to attain
      high coverage levels by timely vaccination, thus, accurate information should be
      delivered and a systematic approach should be targeted to high-risk groups.

PMID- 24013711
TI  - Pathways of Breast Cancer Screening Among Chinese American Women.
AB  - OBJECTIVE: The purpose of this community-based study was to develop a structural
      equation model for factors contributing to breast cancer screening among Chinese
      American women. METHODS: A cross-sectional design included a sample of 440
      Chinese American women aged 40 years and older. The initial step involved use of
      confirmatory factor analysis, which included the following variables:
      access/satisfaction with health care, enabling, predisposing, and cultural and
      health belief factors. Structural equation model analyses were conducted to
      evaluate factors related to breast cancer screening in Chinese American women.
      RESULTS: Initial univariate analyses indicated that women without health
      insurance were significantly more likely to report being never-screened compared
      to women with health insurance. Structural equation modeling techniques were used
      to evaluate the utility of the Sociocultural Health Behavior model in
      understanding breast cancer screening among Chinese American women. Results
      indicated that enabling and predisposing factors were significantly and
      positively related to breast cancer screening. Cultural factors were
      significantly associated with enabling factors and satisfaction with healthcare.
      Overall, the proposed model explained 34% of the variance in breast cancer
      screening among Chinese American women. CONCLUSIONS: The model highlights the
      significance of enabling and predisposing factors in understanding breast cancer
      screening behaviors among Chinese American women. In addition, cultural factors
      were associated with enabling factors, reinforcing the importance of providing
      translation assistance to Chinese women with poor English fluency and increasing
      awareness of the critical role of breast cancer screening. Partnering with
      community organizations may help to facilitate and enhance the screening rates.

PMID- 24013712
TI  - Preoperative platelet count in esophageal squamous cell carcinoma: is it a
      prognostic factor?
AB  - PURPOSE: Platelet count is inversely related to prognosis in many cancers;
      however, its role in esophageal cancer is still controversial. The purpose of
      this study was to determine the prognostic value of preoperative platelet count
      in esophageal squamous cell carcinoma (ESCC). METHODS: From January 2006 to
      December 2008, a retrospective analysis of 425 consecutive patients with ESCC was
      conducted. A receiver operating characteristic (ROC) curve for survival
      prediction was plotted to verify the optimum cutoff point for preoperative
      platelet count. Univariate and multivariate analyses were performed to evaluate
      the prognostic parameters. RESULTS: A ROC curve for survival prediction was
      plotted to verify the optimum cutoff point for platelet count, which was 205 (*
      10(9)/L). Patients with platelet count <= 205 had a significantly better 5-year
      survival than patients with a platelet count >205 (60.7 vs. 31.6 %, P < 0.001).
      The 5-year survival of patients either with platelet count <= 205 or >205 were
      similar (68.6 vs. 58.8 %, P = 0.085) when the nodes were negative. However, the 5
      year survival of patients with platelet count <= 205 was better than that of
      patients with a platelet count >205 when the nodes were involved (32.0 vs. 12.7
      %, P = 0.004). Multivariate analysis showed that platelet count (P = 0.013), T
      grade (P = 0.017), and N staging (P < 0.001) were independent prognostic factors.
      CONCLUSIONS: Preoperative platelet count is a predictive factor for long-term
      survival in ESCC, especially in nodal-positive patients. We conclude that 205
      (*10(9)/L) may be the optimum cutoff point for platelet count in predicting
      survival in ESCC patients.

PMID- 24013713
TI  - Immunosuppression-associated pathology.

PMID- 24013714
TI  - Reversible diffusion restriction of the middle cerebellar peduncles and dentate
      nucleus in acute respiratory syncytial virus cerebellitis: a case report.
AB  - Acute cerebellitis is a postinfectious or postvaccinal disorder that
      predominantly affects children. The typical magnetic resonance imaging appearance
      has been previously described as cerebellar hemispheric cortical edema. Here, we
      report a rare case of respiratory syncytial virus-related cerebellitis with
      transient diffusion restriction of cerebellar peduncles and dentate nucleus.
      Differential diagnoses are also discussed. 

PMID- 24013715
TI  - Interleukin-21, a potential diagnostic and therapeutic target for systemic lupus
      erythematosus.

PMID- 24013716
TI  - QHREDGS enhances tube formation, metabolism and survival of endothelial cells in
      collagen-chitosan hydrogels.
AB  - Cell survival in complex, vascularized tissues, has been implicated as a major
      bottleneck in advancement of therapies based on cardiac tissue engineering. This
      limitation motivates the search for small, inexpensive molecules that would
      simultaneously be cardio-protective and vasculogenic. Here, we present peptide
      sequence QHREDGS, based upon the fibrinogen-like domain of angiopoietin-1, as a
      prime candidate molecule. We demonstrated previously that QHREDGS improved
      cardiomyocyte metabolism and mitigated serum starved apoptosis. In this paper we
      further demonstrate the potency of QHREDGS in its ability to enhance endothelial
      cell survival, metabolism and tube formation. When endothelial cells were exposed
      to the soluble form of QHREDGS, improvements in endothelial cell barrier
      functionality, nitric oxide production and cell metabolism (ATP levels) in serum
      starved conditions were found. The functionality of the peptide was then examined
      when conjugated to collagen-chitosan hydrogel, a potential carrier for in vivo
      application. The presence of the peptide in the hydrogel mitigated paclitaxel
      induced apoptosis of endothelial cells in a dose dependent manner. Furthermore,
      the peptide modified hydrogels stimulated tube-like structure formation of
      encapsulated endothelial cells. When integrin alphavbeta3 or alpha5beta1 were
      antibody blocked during cell encapsulation in peptide modified hydrogels, tube
      formation was abolished. Therefore, the dual protective nature of the novel
      peptide QHREDGS may position this peptide as an appealing augmentation for
      collagen-chitosan hydrogels that could be used for biomaterial delivered cell
      therapies in the settings of myocardial infarction.

PMID- 24013717
TI  - Obesity phenotype is related to NLRP3 inflammasome activity and immunological
      profile of visceral adipose tissue.
AB  - AIMS/HYPOTHESIS: Obesity is a heterogeneous condition comprising both individuals
      who remain metabolically healthy (MHO) and those who develop metabolic disorders
      (metabolically unhealthy, MUO). Adipose tissue is also heterogeneous in that its
      visceral component is more frequently associated with metabolic dysfunction than
      its subcutaneous component. The development of metabolic disorders is partly
      mediated by the NLR family pyrin domain containing-3 (NLRP3) inflammasome, which
      increases the secretion of inflammatory cytokines via activation of caspase-1. We
      compared the immunological profile and NLRP3 activity in adipose tissue between
      MUO and MHO individuals. METHODS: MHO and MUO phenotypes were defined,
      respectively, as the absence and the presence of the metabolic syndrome. Cellular
      composition and intrinsic inflammasome activity were investigated by flow
      cytometry, quantitative RT-PCR and tissue culture studies in subcutaneous and
      visceral adipose tissue from 23 MUO, 21 MHO and nine lean individuals. RESULTS:
      We found significant differences between the three study groups, including an
      increased secretion of IL-1beta, increased expression of IL1B and NLRP3,
      increased number of adipose tissue macrophages and decreased number of regulatory
      T cells in the visceral adipose tissue of MUO patients compared with MHO and lean
      participants. In macrophages derived from visceral adipose tissue, both caspase-1
      activity and IL-1beta levels were higher in MUO patients than in MHO patients.
      Furthermore, caspase-1 activity was higher in CD11c(+)CD206(+) adipose tissue
      macrophages than in CD11c(-)CD206(+) cells. CONCLUSIONS/INTERPRETATION: The MUO
      phenotype seems to be associated with an increased activation of the NLPR3
      inflammasome in macrophages infiltrating visceral adipose tissue, and a less
      favourable inflammatory profile compared with the MHO phenotype.

PMID- 24013718
TI  - Anterior versus posterior approach for treatment of thoracolumbar burst
      fractures: a meta-analysis.
AB  - PURPOSE: To critically review and summarize the literature comparing the results
      of surgery via an anterior approach and that via a posterior approach for the
      treatment of thoracolumbar burst fractures to identify the better approach.
      METHODS: In this meta-analysis, we conducted electronic searches of MEDLINE,
      EMBASE, the Cochrane Central Register of Controlled Trials and other databases
      using the search terms "thoracolumbar fractures", "anterior", "posterior",
      "controlled clinical trials". Relevant journals or conference proceedings were
      also searched manually. Data extraction and quality assessment were in accordance
      with Cochrane Collaboration guidelines. The analysis was performed on individual
      patient data from all the trials that met the selection criteria. Sensitivity
      analysis was performed when there was significant heterogeneity. Results were
      expressed as risk difference for dichotomous outcomes and mean difference for
      continuous outcomes with 95 % confidence interval. RESULTS: Four randomized
      clinical trials and three controlled clinical trials comparing the results of the
      anterior versus posterior approach in the treatment of thoracolumbar burst
      fractures were retrieved; these studies included 179 and 152 patients in the
      anterior and posterior approach groups, respectively. There were no differences
      in terms of neurological recovery, return to work, complications and Cobb angle
      between the two groups. The anterior approach was associated with longer
      operative time, greater blood loss and higher cost than the posterior approach.
      CONCLUSIONS: The posterior approach may be more effective than the anterior
      approach. However, more high-quality, randomized controlled trials are required
      to compare these approaches and guide clinical decision-making. Level of Evidence
      Level II, therapeutic study. See the Guidelines for Authors for a complete
      description of level of evidence.

PMID- 24013719
TI  - The combination of mesenchymal stem cells and a bone scaffold in the treatment of
      vertebral body defects.
AB  - PURPOSE: Vertebral body defects represent one of the most common orthopedic
      challenges. In order to advance the transfer of stem cell therapies into
      orthopedic clinical practice, we performed this study to evaluate the safety and
      efficacy of a composite bioartificial graft based on a hydroxyapatite bone
      scaffold (CEM-OSTETIC((r))) combined with human mesenchymal stem cells (MSCs) in
      a rat model of vertebral body defects. METHODS: Under general isoflurane
      anesthesia, a defect in the body of the L2 vertebra was prepared and left to heal
      spontaneously (group 1), implanted with scaffold material alone (group 2), or
      implanted with a scaffold together with 0.5 million MSCs (group 3) or 5 million
      MSCs (group 4). The rats were killed 8 weeks after surgery. Histological and
      histomorphometrical evaluation of the implant as well as micro-CT imaging of the
      vertebrae were performed. RESULTS: We observed a significant effect on the
      formation of new bone tissue in the defect in group 4 when compared to the other
      groups and a reduced inflammatory reaction in both groups receiving a scaffold
      and MSCs. We did not detect any substantial pathological changes or tumor
      formation after graft implantation. CONCLUSIONS: MSCs in combination with a
      hydroxyapatite scaffold improved the repair of a model bone defect and might
      represent a safe and effective alternative in the treatment of vertebral bone
      defects.

PMID- 24013720
TI  - Biomechanical comparison of laminectomy, hemilaminectomy and a new minimally
      invasive approach in the surgical treatment of multilevel cervical intradural
      tumour: a finite element analysis.
AB  - PURPOSE: The objective of this study was to investigate the impact of the less
      invasive procedures of hemilaminectomy and unilateral multilevel interlaminar
      fenestration (UMIF) on the cervical spinal biomechanics. METHODS: A validated
      nonlinear finite element model of the intact cervical spine (C2-C7) was modified
      to study the biomechanical changes as a result of surgical alteration for
      treatment of intradural tumours at C3-6 using multilevel laminectomy (ML),
      multilevel hemilaminectomy (MHL) and UMIF with or without unilateral graded
      facetectomy. RESULTS: Under the load-controlled method, the greatest
      biomechanical changes occurred at the surgical segments. The largest increases
      occurred in flexion motions following ML approach with 70, 62 and 60 % increase
      at C3-4, C4-5 and C5-6, respectively. The increases were significantly reduced to
      no more than 14 % under MHL and UMIF. When combined with graded facetectomy, the
      changes in flexion under ML approach have a significantly further increase, up to
      110 % at C3-4. The further increase was not significantly following MHL and UMIF,
      with no more than 31 % increase at C3-4, C4-5 and C5-6. The motion following UMIF
      was only slightly smaller in axial rotation than MHL. The maximum stresses in the
      annulus occurred during flexion in ML model, with 39, 34 and 38 % more stress
      than the intact at C3-4, C4-5 and C5-6, respectively. The increases of stress
      were significantly reduced to 5-7 % under MHL and UMIF. CONCLUSIONS: The less
      invasive approaches of UMIF and MHL greatly preserved the flexion motion (more
      than 48 %) of the cervical spine compared with laminectomy, and the preserved
      motion mean the low-risk of postoperative spinal instability. UMIF and MHL also
      reduced the increased stress of annulus caused by ML, and the lesser stress will
      lower the risk of postoperative disc degeneration. The posterior bone elements
      play a slight role in spinal stability after removal of the attached ligaments.

PMID- 24013721
TI  - The EMT activator ZEB1 promotes tumor growth and determines differential response
      to chemotherapy in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is a B-cell malignancy characterized by a poor
      response to treatment and prognosis. Constitutive activation of different
      signaling pathways in subsets of MCLs, through genetic and/or nongenetic
      alterations, endows tumor cells with enhanced proliferation and reduced
      apoptosis. The canonical Wnt pathway (beta-catenin/TCF-LEF), implicated in the
      pathogenesis of numerous cancers, is constitutively active in half of MCLs. Here,
      we show that ZEB1, a transcription factor better known for promoting metastasis
      in carcinomas, is expressed in primary MCLs with active Wnt signaling. ZEB1
      expression in MCL cells depends on Wnt, being downregulated by beta-catenin
      knockdown or blocking of Wnt signaling by salinomycin. Knockdown of ZEB1 reduces
      in vitro cell viability and proliferation in MCL cells, and, importantly, tumor
      growth in mouse xenograft models. ZEB1 activates proliferation-associated (HMGB2,
      UHRF1, CENPF, MYC, MKI67, and CCND1) and anti-apoptotic (MCL1, BCL2, and BIRC5)
      genes and inhibits pro-apoptotic ones (TP53, BBC3, PMAIP1, and BAX). We show that
      ZEB1 expression in MCL cells determines differential resistance to chemotherapy
      drugs and regulates transporters involved in drug influx/efflux. Downregulation
      of ZEB1 by salinomycin increases the sensitivity of MCL cells to the cytotoxic
      effect of doxorubicin, cytarabine and gemcitabine. Lastly, salinomycin and
      doxorubicin display a synergistic effect in established and primary MCL cells.
      These results identify ZEB1 in MCL where it promotes cell proliferation, enhanced
      tumor growth and a differential response to chemotherapy drugs. ZEB1 could thus
      potentially become a predictive biomarker and therapeutic target in this
      lymphoma. 

PMID- 24013723
TI  - An appointment with death, : 2013 Cold Spring Harbor Asia meeting 'mechanisms and
      functions of non-apoptotic cell death'.

PMID- 24013722
TI  - DeltaNp63 regulates select routes of reprogramming via multiple mechanisms.
AB  - Somatic cells can be converted into induced pluripotent stem cells (iPSCs) by
      forced expression of various combinations of transcription factors, but the
      molecular mechanisms of reprogramming are poorly understood. Specifically,
      evidence that the reprogramming process can take many distinct routes only begins
      to emerge. It is definitively established that p53 deficiency greatly enhances
      reprogramming, revealing p53's barrier function for induced pluripotency, but the
      role of its homologs p63 and p73 are unknown. Here we report that in stark
      contrast to p53, p73 has no role in reprogramming. However, p63 is an enabling
      (rather than a barrier) factor for Oct4, Sox2 and Klf4 (OSK) and Oct4 and Sox2
      (OS), but not for Oct4 and Klf4 (OK) reprogramming of mouse embryonic
      fibroblasts. Specifically, p63 is essential during reprogramming for maximum
      efficiency, albeit not for the ability to reprogram per se, and is dispensable
      for maintaining stability and pluripotency of established iPSC colonies.
      DeltaNp63, but not TAp63, is the principal isoform involved. Loss of p63 can
      affect reprogramming via several mechanisms such as reduced expression of
      mesenchymal-epithelial transition and pluripotency genes, hypoproliferation and
      loss of the most reprogrammable cell populations. During OSK and OS
      reprogramming, different mechanisms seem to be critical, such as regulation of
      epithelial and pluripotency genes in OSK reprogramming versus regulation of
      proliferation in OS reprogramming. Finally, our data reveal three different
      routes of reprogramming by OSK, OS or OK, based on their differential p63
      requirements for iPSC efficiency and pluripotency marker expression. This
      supports the concept that many distinct routes of reprogramming exist. 

PMID- 24013724
TI  - PCAF ubiquitin ligase activity inhibits Hedgehog/Gli1 signaling in p53-dependent
      response to genotoxic stress.
AB  - The Hedgehog (Hh) signaling regulates tissue development, and its aberrant
      activation is a leading cause of malignancies, including medulloblastoma (Mb). Hh
      dependent tumorigenesis often occurs in synergy with other mechanisms, such as
      loss of p53, the master regulator of the DNA damage response. To date, little is
      known about mechanisms connecting DNA-damaging events to morphogen-dependent
      processes. Here, we show that genotoxic stress triggers a cascade of signals,
      culminating with inhibition of the activity of Gli1, the final transcriptional
      effector of Hh signaling. This inhibition is dependent on the p53-mediated
      elevation of the acetyltransferase p300/CBP-associated factor (PCAF). Notably, we
      identify PCAF as a novel E3 ubiquitin ligase of Gli1. Indeed PCAF, but not a
      mutant with a deletion of its ubiquitination domain, represses Hh signaling in
      response to DNA damage by promoting Gli1 ubiquitination and its proteasome
      dependent degradation. Restoring Gli1 levels rescues the growth arrest and
      apoptosis effect triggered by genotoxic drugs. Consistently, DNA-damaging agents
      fail to inhibit Gli1 activity in the absence of either p53 or PCAF. Finally, Mb
      samples from p53-null mice display low levels of PCAF and upregulation of Gli1 in
      vivo, suggesting PCAF as potential therapeutic target in Hh-dependent tumors.
      Together, our data define a mechanism of inactivation of a morphogenic signaling
      in response to genotoxic stress and unveil a p53/PCAF/Gli1 circuitry centered on
      PCAF that limits Gli1-enhanced mitogenic and prosurvival response. 

PMID- 24013725
TI  - DNA damage leads to progressive replicative decline but extends the life span of
      long-lived mutant animals.
AB  - Human-nucleotide-excision repair (NER) deficiency leads to different
      developmental and segmental progeroid symptoms of which the pathogenesis is only
      partially understood. To understand the biological impact of accumulating
      spontaneous DNA damage, we studied the phenotypic consequences of DNA-repair
      deficiency in Caenorhabditis elegans. We find that DNA damage accumulation does
      not decrease the adult life span of post-mitotic tissue. Surprisingly, loss of
      functional ERCC-1/XPF even further extends the life span of long-lived daf-2
      mutants, likely through an adaptive activation of stress signaling. Contrariwise,
      NER deficiency leads to a striking transgenerational decline in replicative
      capacity and viability of proliferating cells. DNA damage accumulation induces
      severe, stochastic impairment of development and growth, which is most pronounced
      in NER mutants that are also impaired in their response to ionizing radiation and
      inter-strand crosslinks. These results suggest that multiple DNA-repair pathways
      can protect against replicative decline and indicate that there might be a direct
      link between the severity of symptoms and the level of DNA-repair deficiency in
      patients. 

PMID- 24013726
TI  - Potent and multiple regulatory actions of microglial glucocorticoid receptors
      during CNS inflammation.
AB  - In CNS, glucocorticoids (GCs) activate both GC receptor (GR) and
      mineralocorticoid receptor (MR), whereas GR is widely expressed, the expression
      of MR is restricted. However, both are present in the microglia, the resident
      macrophages of the brain and their activation can lead to pro- or anti
      inflammatory effects. We have therefore addressed the specific functions of GR in
      microglia. In mice lacking GR in macrophages/microglia and in the absence of
      modifications in MR expression, intraparenchymal injection of lipopolysaccharide
      (LPS) activating Toll-like receptor 4 signaling pathway resulted in exacerbated
      cellular lesion, neuronal and axonal damage. Global inhibition of GR by RU486 pre
      treatment revealed that microglial GR is the principal mediator preventing
      neuronal degeneration triggered by lipopolysaccharide (LPS) and contributes with
      GRs of other cell types to the protection of non-neuronal cells. In vivo and in
      vitro data show GR functions in microglial differentiation, proliferation and
      motility. Interestingly, microglial GR also abolishes the LPS-induced delayed
      outward rectifier currents by downregulating Kv1.3 expression known to control
      microglia proliferation and oxygen radical production. Analysis of GR
      transcriptional function revealed its powerful negative control of pro
      inflammatory effectors as well as upstream inflammatory activators. Finally, we
      analyzed the role of GR in chronic unpredictable mild stress and aging, both
      known to prime or sensitize microglia in vivo. We found that microglial GR
      suppresses rather than mediates the deleterious effects of stress or aging on
      neuronal survival. Overall, the results show that microglial GR acts on several
      key processes limiting pro-inflammatory actions of activated microglia. 

PMID- 24013727
TI  - TLR9 independent interferon alpha production by neutrophils on NETosis in
      response to circulating chromatin, a key lupus autoantigen.
AB  - OBJECTIVES: Interferon (IFN) alpha is a key immunoregulatory cytokine secreted by
      activated plasmacytoid dendritic cells (PDC) that constitute less than 1% of
      leucocytes. IFNalpha plays an important role in the pathogenesis of systemic
      lupus erythematosus (SLE). Nevertheless, the natural IFNalpha inducers in SLE as
      well as the different IFNalpha secreting cell types are only partially
      characterised. METHODS: Chromatin was purified from calf thymus. Human peripheral
      blood mononuclear cells (PBMC), neutrophils and mouse bone marrow neutrophils
      were purified and cultured with different stimuli. IFNalpha production was
      estimated by flow cytometry, ELISA and a bioassay, and gene expression by
      quantitative real time PCR. Neutrophil activation and NETosis were analysed by
      flow cytometry, ELISA and confocal microscopy. RESULTS: Neutrophils produced a
      bioactive IFNalpha on stimulation with purified chromatin. IFNalpha secretion was
      observed with steady state neutrophils purified from 56 independent healthy
      individuals and autoimmune patients in response to free chromatin and not
      chromatin containing immune complexes. Chromatin induced IFNalpha secretion
      occurred independently of Toll-like receptor 9 (TLR9). Neutrophil priming by
      granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating
      factor or IFNalpha was not necessary but PBMC sustained IFNalpha secretion by
      neutrophils. PDC were 27 times more efficient than neutrophils but blood
      neutrophils were 100 times more frequent than PDC. Finally, neutrophil activation
      by chromatin was associated with NETosis and DNA sensor upregulation.
      CONCLUSIONS: Neutrophils have the capability of producing IFNalpha on selective
      triggering, and we identified a natural lupus stimulus involved, unveiling a new
      mechanism involved in SLE. Neutrophils represent another important source of
      IFNalpha and important targets for future therapies aimed at influencing IFNalpha
      levels.

PMID- 24013728
TI  - Levels of target activation predict antifibrotic responses to tyrosine kinase
      inhibitors.
AB  - OBJECTIVES: To assess whether the discrepancy between the strong antifibrotic
      effects of tyrosine kinase inhibitors (TKIs) in animal models and the
      inconsistent results in clinical studies might be related to the activation
      levels of drug targets. METHODS: Skin sections of bleomycin, TSK1, Fra-2
      transgenic mice, SSc patients and controls were analysed by histology and
      immunohistochemistry. Subgroups of mice were treated with the TKIs nilotinib or
      imatinib. Differences in the activation levels of the TKI targets p-PDGFRbeta
      (platelet derived growth factor beta) and p-c-abl were assessed. RESULTS: In
      bleomycin and TSK1 mice, expression of activated p-PDGFRbeta (platelet derived
      growth factor receptor beta) and p-c-abl was ubiquitous with strong upregulation
      compared with controls. Treatment with TKIs resulted in successful target
      inhibition and consequently reduced dermal fibrosis. In the Fra-2 model, the
      activation levels of p-PDGFRbeta and p-c-abl were much lower than in the
      bleomycin and the TSK1 models. Accordingly, nilotinib did not prevent dermal
      fibrosis and target inhibition was unsuccessful. Notably, in skin biopsies of SSc
      patients, the mean activation levels of TKI targets were only moderate and in the
      majority of patients resembled those of the non-responsive Fra-2 model.
      CONCLUSIONS: Animal models for proof-of-concept studies should be selected based
      on a similar activation level and expression pattern of drug targets as in human
      SSc.

PMID- 24013729
TI  - Formation of single-walled bimetallic coinage alloy nanotubes in confined carbon
      nanotubes: molecular dynamics simulations.
AB  - The growth of single-walled bimetallic Au-Ag, Au-Cu and Ag-Cu alloy nanotubes
      (NTs) and nanowires (NWs) in confined carbon nanotubes (CNTs) has been
      investigated by using the classical molecular dynamics (MD) method. It is found
      that three kinds of single-walled gold-silver, gold-copper and silver-copper
      alloy NTs could indeed be formed in confined CNTs at any alloy concentration,
      whose geometric structures are less sensitive to the alloy concentration. And an
      extra nearly pure Au (Cu) chain will exist at the center of Au-Ag (Au-Cu and Ag
      Cu) NTs when the diameters of the outside CNTs are big enough, thus producing a
      new type of tube-like alloy NWs. The bonding energy differences between the mono-
      and hetero-elements of the coinage metal atoms and the quasi-one-dimensional
      confinement from the CNT play important roles in suppressing effectively the
      "self-purification" effects, leading to formation of these coinage alloy NTs. In
      addition, the fluid-solid phase transition temperatures of the bimetallic alloy
      NTs are found to locate between those of the corresponding pure metal tubes.
      Finally, the dependences of the radial breathing mode (RBM) frequencies and the
      tube diameters of the alloy NTs on the alloying concentration were obtained,
      which will be very helpful for identifying both the alloying concentration and
      the alloy tube diameters in future experiments. 

PMID- 24013730
TI  - Privacy and protection in the genomic era.

PMID- 24013731
TI  - After 40 years, fate of recombinant DNA committee under review.

PMID- 24013732
TI  - Longer exclusivity sought for fixed-dose drug combinations.

PMID- 24013733
TI  - First vaccines targeting 'cruise ship virus' sail into clinical trials.

PMID- 24013734
TI  - 'Molecular biocontainment' proposed to ease flu research worry.

PMID- 24013736
TI  - Flurry of deal-making surrounds new autoimmunity target.

PMID- 24013737
TI  - Pipeline for COPD drugs flows with combination candidates.

PMID- 24013739
TI  - Straight talk with...Jonathan Quick. Interview by Roxanne Khamsi.
AB  - In April 2012, an e-mail announcing the impending closure of the Global Health
      Council following the cancellation of its annual conference sent shockwaves
      through its community of 325 organizational members spanning 39 countries. For 40
      years, the Alexandria, Virginia-based nonprofit had acted as an umbrella
      organization for stakeholders that include some of the world's most prominent
      medical institutions and drug companies. As the June 2012 closure of the GHC
      approached, several members stepped in to rescue the operation, including
      Jonathan Quick, a family physician and CEO of Management Sciences for Health, a
      Cambridge, Massachusetts-based outfit that works to strengthen health systems and
      infrastructure around the globe. In January, a new GHC board was elected, with
      Quick at the helm. In the ensuing months the board members have built the
      organization back up-albeit as a leaner and more targeted operation. This past
      summer, they launched a revamped website (www.globalhealth.org) and are looking
      ahead to convening GHC members at the UN General Assembly on 18 September in New
      York, where the discussion of Millennium Development Goals will take place. As
      Nature Medicine went to press, the relaunched GHC was in the midst of recruiting
      for its first staff position, executive director. Roxanne Khamsi spoke with Quick
      about the health of the organization.

PMID- 24013740
TI  - Aura of mystery.
AB  - It begins as a slowly expanding spot of light or similar visual disturbance,
      often accompanied by phantom noises and other sensory distortions. People who
      experience such 'auras' know all too well that these early warning signs will
      culminate in a head-splitting migraine, yet scientists have little idea what
      causes the debilitating deluge of symptoms. Elie Dolgin talks to neurologists
      hoping to change that - by triggering auras in the laboratory in order to study
      them.

PMID- 24013741
TI  - Scientists: you really need to get out of the lab more.

PMID- 24013743
TI  - Alzheimer's and prion diseases: PDK1 at the crossroads.
AB  - TACE-mediated proteolysis is a key event interfering with both Alzheimer's and
      prion diseases. A new study shows that phosphoinositide-dependent kinase-1 (PDK1)
      is activated by cellular prion protein, which alters membrane-associated TACE
      levels, thereby influencing both Alzheimer's and prion pathologies.

PMID- 24013744
TI  - Forever (FGF) 21.
AB  - The fibroblast growth factor 21 (FGF21)-beta-Klotho pathway orchestrates a switch
      to oxidative metabolism during fasting and starvation and has been implicated as
      a signal connecting nutrition, growth, reproduction and longevity. Two new
      studies in mice show that Fgf21 interacts directly with the brain circadian clock
      to coordinate activity and reproduction as part of the adaptation to fasting.

PMID- 24013745
TI  - IL-17 mediates resistance to anti-VEGF therapy.
AB  - Interleukin-17 (IL-17) released in the tumor microenvironment in response to
      drugs blocking vascular endothelial growth factor (VEGF) triggers stromal-derived
      inflammatory and VEGF-independent angiogenic programs that induce the drug
      refractoriness found in cancers resistant to anti-angiogenic therapy.

PMID- 24013746
TI  - Proliferating macrophages prevail in atherosclerosis.
AB  - Macrophages accumulate in atherosclerotic lesions during the inflammation that is
      part of atherosclerosis development and progression. A new study in mice
      indicates that the accumulation of macrophages in atherosclerotic plaques depends
      on local macrophage proliferation rather than the recruitment of circulating
      monocytes.

PMID- 24013747
TI  - Assessing the potential of induced liver regeneration.

PMID- 24013748
TI  - Immunotherapy at large: the road to personalized cancer vaccines.

PMID- 24013749
TI  - Immunotherapy at large: Balancing tumor immunity and inflammatory pathology.

PMID- 24013756
TI  - Roadblocks to translational advances on metastasis research.
AB  - Promising advances in cancer therapy stemming from an increasing understanding of
      the molecular and genetic underpinnings of the tumorigenic process have been
      fueled by a strong, determined scientific community, influential patient advocacy
      groups and committed funding bodies. Despite these efforts, the development of
      effective drugs to prevent systemic dissemination of cancer cells or to eliminate
      overt metastasis in secondary organs remains a challenge to both researchers and
      physicians. In an attempt to tackle the most relevant and timely translational
      issues, a meeting held in 2012 as a result of a successful partnership between
      the Volkswagen Foundation and Nature Medicine brought together a group of
      metastasis research experts to identify the most important hurdles and help
      create a framework for potential clinical and translational strategies.

PMID- 24013757
TI  - Mitochondrial respiratory chain and creatine kinase activities following trauma
      brain injury in brain of mice preconditioned with N-methyl-D-aspartate.
AB  - Traumatic brain injury (TBI) induces glutamatergic excitotoxicity through N
      methyl-D-aspartate (NMDA) receptors, affecting the integrity of the mitochondrial
      membrane. Studies have pointed to mitochondria as the master organelle in the
      preconditioning-triggered endogenous neuroprotective response. The present study
      is aimed at understanding energy metabolism in the brains of mice after
      preconditioning with NMDA and TBI. For this purpose, male albino CF-1 mice were
      pre-treated with NMDA (75 mg/kg) and subjected to brain trauma. Mitochondrial
      respiratory chain and creatine kinase activities were assessed at 6 or 24 h after
      trauma. The mice preconditioned and subjected to TBI exhibited augmented
      activities of complexes II and IV in the cerebral cortex and/or cerebellum.
      Creatine kinase activity was also augmented in the cerebral cortex after 24 h. We
      suggest that even though NMDA preconditioning and TBI have similar effects on
      enzyme activities, each manage their response via opposite mechanisms because the
      protective effects of preconditioning are unambiguous. In conclusion, NMDA
      preconditioning induces protection via an increase of enzymes in the
      mitochondria. 

PMID- 24013758
TI  - Regulation of mineral metabolism by lithium.
AB  - Lithium, an inhibitor of glycogen synthase kinase 3 (GSK3), is widely used for
      the treatment of mood disorders. Side effects of lithium include nephrogenic
      diabetes insipidus, leading to renal water loss. Dehydration has in turn been
      shown to downregulate Klotho, which is required as co-receptor for the
      downregulation of 1,25(OH)2D3 formation by fibroblast growth factor 23 (FGF23).
      FGF23 decreases and 1,25(OH)2D3 stimulates renal tubular phosphate reabsorption.
      The present study explored whether lithium influences renal Klotho expression,
      FGF23 serum levels, 1,25(OH)2D3 formation, and renal phosphate excretion. To this
      end, mice were analyzed after a 14-day period of sham treatment or of treatment
      with lithium (200 mg/kg/day subcutaneously). Serum antidiuretic hormone (ADH),
      FGF23, and 1,25(OH)2D3 concentrations were determined by ELISA or EIA, renal
      Klotho protein abundance and GSK3 phosphorylation were analyzed by Western
      blotting, and serum phosphate and calcium concentration by photometry. Lithium
      treatment significantly increased renal GSK3 phosphorylation, enhanced serum ADH
      and FGF23 concentrations, downregulated renal Klotho expression, stimulated renal
      calcium and phosphate excretion, and decreased serum 1,25(OH)2D3 and phosphate
      concentrations. In conclusion, lithium treatment upregulates FGF23 formation, an
      effect paralleled by substantial decrease of serum 1,25(OH)2D3, and phosphate
      concentrations and thus possibly affecting tissue calcification. 

PMID- 24013759
TI  - Efficiency and cross-bridge work output of skeletal muscle is decreased at low
      levels of activation.
AB  - The purpose of this study was to determine how the mechanical efficiency of
      skeletal muscle is affected by level of activation. Experiments were performed in
      vitro (35  degrees C) using bundles of fibres from fast-twitch extensor digitorum
      longus (EDL) and slow-twitch soleus muscles of mice. Measurements were made of
      the total work and heat produced in response to 10 brief contractions. Mechanical
      efficiency was the ratio of total work performed to (total heat produced + work
      performed). Level of activation was varied by altering stimulation frequency
      between 40 and 160 Hz. Efficiency did not differ significantly between the two
      muscle types but was significantly lower using 40 Hz stimulation (mean efficiency
      +/- SEM, 0.092 +/- 0.012, n = 12, averaged across EDL and soleus) than at any of
      the other frequencies (160 Hz: 0.147 +/- 0.007, n = 12). Measurements of the
      partitioning of energy output between force-dependent and force-independent
      components enabled calculation of the amount of Ca(2+) released and number of
      cross-bridge cycles performed during the contractions. At 40 Hz stimulation
      frequency, less Ca(2+) was released than at higher frequencies and fewer cross
      bridge cycles were performed. Furthermore, less work was performed in each cross
      bridge cycle. It is concluded that skeletal muscles are less efficient at low
      levels of activation than when fully activated and this indicates that level of
      activation affects not only the number of cycling cross-bridges but also the
      ability of individual cross-bridges to perform work. 

PMID- 24013760
TI  - Hand tapping at mixed frequencies requires more motor cortex activity compared to
      single frequencies: an fNIRS study.
AB  - Fast cyclic movements and discrete motor acts are controlled differently,
      presumably because fast cyclic tasks are more automated, thereby depending on
      different circuits. If fast cyclic movements are made less predictable (e.g., by
      mixing frequencies), one would predict that their control will be less automated,
      requiring increased activity in motor cortical areas. The present functional near
      infrared spectroscopy (fNIRS) study investigated whether switching between
      frequencies increases the motor cortex activity compared to movements at single
      rates. Therefore, hand tapping at mixed frequencies ("mixed") was compared with
      hand tapping at 0.4 ("low frequency"), 0.8 ("mid-frequency"), and 1.4 Hz ("high
      frequency"). Oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) concentration
      changes were studied in eleven healthy subjects with eight-channel fNIRS covering
      the hand motor cortex. Repeated-measures ANOVAs revealed significant main effects
      for the type of task in HbO and HbR. Post hoc analysis showed a larger HbO
      increase and HbR decrease for the mixed task compared to the low- and high
      frequency conditions. In addition, the mid-frequency condition revealed a smaller
      HbR decrease compared to the mixed task. Single frequency data indicated the
      existence of separate motor control systems for low- and high-frequency
      movements. The increased activity for the mixed task is suggested to be the
      result of the recruitment of a voluntary command motor system instead of
      automated systems.

PMID- 24013761
TI  - Wood chemistry analysis and expression profiling of a poplar clone expressing a
      tyrosine-rich peptide.
AB  - KEY MESSAGE: Our study has identified pathways and gene candidates that may be
      associated with the greater flexibility and digestibility of the poplar cell
      walls. With the goal of facilitating lignin removal during the utilization of
      woody biomass as a biofuel feedstock, we previously transformed a hybrid poplar
      clone with a partial cDNA sequence encoding a tyrosine- and hydroxyproline-rich
      glycoprotein from parsley. A number of the transgenic lines released more
      polysaccharides following protease digestion and were more flexible than wild
      type plants, but otherwise normal in phenotype. Here, we report that
      overexpression of the tyrosine-rich peptide encoding sequence in these transgenic
      poplar plants did not significantly alter total lignin quantity or quality (S/G
      lignin ratio), five- and six-carbon sugar contents, growth rate, or
      susceptibility to a major poplar fungal pathogen, Septoria musiva. Whole-genome
      microarray analysis revealed a total of 411 differentially expressed transcripts
      in transgenic lines, all with decreased transcript abundance relative to wild
      type plants. Their corresponding genes were overrepresented in functional
      categories such as secondary metabolism, amino acid metabolism, and energy
      metabolism. Transcript abundance was decreased primarily for five types of genes
      encoding proteins involved in cell-wall organization and in lignin biosynthesis.
      The expression of a subset of 19 of the differentially regulated genes by qRT-PCR
      validated the microarray results. Our study has identified pathways and gene
      candidates that may be the underlying cause for the enhanced flexibility and
      digestibility of the stems of poplar plants expressing the TYR transgene.

PMID- 24013762
TI  - Nitric oxide contributes to copper tolerance by influencing ROS metabolism in
      Arabidopsis.
AB  - KEY MESSAGE: Nitric oxide improves copper tolerance via modulation of superoxide
      and hydrogen peroxide levels. This reflects the necessity of a well-coordinated
      interplay between NO and ROS during stress tolerance. Copper (Cu) excess causes
      toxicity and one probable consequence of this is the disturbance of cell redox
      state maintenance, inter alia, by reactive oxygen- (ROS) and nitrogen species
      (RNS). The objective of this paper was to examine the role of nitric oxide (NO)
      in Cu stress tolerance and its relationship with ROS in Arabidopsis. In agar
      grown seedlings, concentration-dependent Cu accumulation was observed. The 5 MUM
      Cu resulted in reduced cell viability in the NO overproducing nox1 and gsnor1-3
      root tips compared to the wild-type (WT). In contrast, 25 and 50 MUM Cu caused
      higher viability in these mutants, while in the NO-lacking nia1nia2 lower
      viability was detected than in the WT. The exogenous NO donor enhanced cell
      viability and scavenging endogenous NO decreased it in Cu-exposed WT seedlings.
      Besides, SNP in nia1nia2 roots led to the improvement of viability. The ascorbic
      acid-deficient mutants (vtc2-1, vtc2-3) possessing slightly elevated ROS levels
      proved to be Cu sensitive, while miox4 showing decreased ROS production was more
      tolerant to Cu than the WT. In nox1 and gsnor1-3, Cu did not induce superoxide
      formation, and H2O2 accumulation occurred only in the case of NO deficiency.
      Based on these, under mild stress NO intensifies cell injury, while in the case
      of severe Cu excess it contributes to better viability. ROS were found to be
      responsible for aggravation of Cu-induced damage. NO alleviates acute Cu stress
      via modulation of O2(.-) and H2O2 levels reflecting the necessity of a well
      coordinated interplay between NO and ROS during stress tolerance.

PMID- 24013763
TI  - New-generation therapy for ANCA-associated vasculitis.
AB  - Newer therapies for systemic vasculitis are required to improve the efficacy and
      reduce the toxicity associated with current agents. Our understanding of its
      pathogenesis is increasing with the availability of targeted therapies. B-cell
      depletion with rituximab is now a licensed therapy for ANCA vasculitis. Targets
      for therapy currently in development in ANCA associated vasculitis include
      blockade of complement and pro-inflammatory cytokines, and inhibition of T cell
      co-stimulation. 

PMID- 24013764
TI  - Creatinine-based equation to estimate the glomerular filtration rate in Japanese
      children and adolescents with chronic kidney disease.
AB  - BACKGROUND: Renal inulin clearance is the gold standard for evaluation of kidney
      function, but cannot be measured easily in children. Therefore, we utilize the
      serum creatinine (Cr)-based estimated GFR (eGFR) measuring serum Cr by the
      enzymatic method, and we have reported simple serum Cr-based eGFR in Japanese
      children aged between 2 and 11 years old. Furthermore, we should use serum Cr
      based eGFR in Japanese adolescents as well as children with chronic kidney
      disease for evaluation of renal function. METHODS: The inulin clearance and serum
      Cr level determined by an enzymatic method were measured in 131 pediatric chronic
      kidney disease (CKD) patients between the ages of 2 and 18 years old with no
      underlying disease affecting renal function except CKD to determine the serum Cr
      based eGFR in Japanese children and adolescents. RESULTS: We offer the complex
      estimated GFR equation using polynomial formulae for reference serum creatinine
      levels with body length in Japanese children except infants, resulting in the
      following equation:[Formula: see text] Reference serum Cr levels (y) are shown by
      the following two equations of body length (x):[Formula: see text] CONCLUSION:
      The new polynomial eGFR formula showing the relationship with body length and
      serum Cr level may be applicable for clinical screening of renal function in
      Japanese children and adolescents aged between 2 and 18 years.

PMID- 24013766
TI  - Matrix isolation and spectroscopic properties of the methylsulfinyl radical
      CH3(O)S.
AB  - The atmospherically highly relevant methylsulfinyl radical CH3(O)S was generated
      thermally under flash pyrolysis conditions and isolated in Ar matrices at 10 K;
      the allyl radical is a byproduct. CH3(O)S and its D3- and (13)C-isotopologues
      were characterized through the excellent agreement between experimental and
      computed IR and UV/Vis spectra. 

PMID- 24013767
TI  - Planning to avoid risk or planning for a positive life: the relationship between
      release plan valence and reoffending.
AB  - Following release from prison, offenders face a variety of challenges
      reintegrating back into the community. As a result, many high-risk offenders fail
      quickly. Research has shown that good quality release plans-plans to address
      offenders' basic needs in the community-are related to reduced rates of
      recidivism during this risky time. But what makes a good plan? The current study
      examines release plan valence: whether plans are approach-oriented or avoidance
      oriented. Although it was hypothesized that approach plans would be related to
      better outcomes, the results showed no relationship between release plan valence
      and reoffending rates. These results indicate that planning for a positive life
      and plans for risk management are equally important in reducing risk in the
      community. 

PMID- 24013765
TI  - Efficacy and safety of darbepoetin alfa for anemia in children with chronic
      kidney disease: a multicenter prospective study in Japan.
AB  - BACKGROUND: We evaluated the safety and efficacy of darbepoetin alfa (DA), an
      attractive alternative to recombinant human erythropoietin (rHuEPO) in managing
      renal anemia, in Japanese children with chronic kidney disease (CKD) on
      peritoneal dialysis (PD) and hemodialysis (HD), and not on dialysis (ND).
      METHODS: A total of 31 pediatric CKD patients (13 PD, 2 HD, and 16 ND) were
      enrolled. DA was administered bi-weekly intravenously (IV) or subcutaneously (SC)
      for PD or ND patients, and weekly IV for HD patients for 24 weeks. The target Hb
      was defined as 11.0 to <=13.0 g/dl. In patients receiving rHuEPO, the initial DA
      dose was calculated at 1 MUg DA for 200 IU rHuEPO. The initial DA dose for naive
      patients was determined by body weight, and intended not to exceed 0.5 MUg/kg per
      administration. For some PD or ND patients, the dosing frequency was subsequently
      changed to once every 4 weeks. RESULTS: Mean Hb values increased from 10.5 +/-
      1.1 to 11.1 +/- 1.1 g/dl after 4 weeks of DA treatment. The target Hb was
      achieved in all patients, 64.5 % of whom maintained the value at completion of
      the study. Hb responses were similar between IV and SC. The dosing frequency was
      extended to once every 4 weeks in 37.9 % of PD or ND patients. Eighty-seven
      adverse events were noted in 27 (87.1 %) of 31 patients, none of which were
      associated with DA. CONCLUSION: These results suggest that IV or SC
      administration of DA is an effective and safe treatment for renal anemia in
      Japanese children with CKD.

PMID- 24013768
TI  - Psychological strengths and posttraumatic growth in the successful reintegration
      of South African ex-offenders.
AB  - This study aimed to explore the possible presence of psychological strengths and
      posttraumatic growth in the life stories of ex-offenders who desisted returning
      to crime. Recidivism rates in South African offenders released from prison remain
      as high as 97%. Little is known about positive psychological factors that may
      facilitate successful reentry of ex-offenders in the South African context. In an
      exploratory qualitative study, three adult male ex-offenders who had successfully
      reintegrated into society were interviewed, using a semi-structured interview
      schedule focusing on their life stories. Data was analyzed using thematic
      analysis. Several psychological strengths, including hope, gratitude, and
      spirituality, were evident in the responses of the participants. Furthermore,
      they seemed to experience a sense of posttraumatic growth. Identifying
      psychological strengths, including character strengths, may add to understanding
      and facilitating successful reintegration of ex-offenders. From these preliminary
      findings, implications for practice and research are proposed. 

PMID- 24013769
TI  - Prevalence and risk factors for self-reported violence of Osaka and Seattle male
      youths.
AB  - Traditionally, Japan has been regarded as a country with low crime. Comparative
      research has given insights into the extent of similarities and differences in
      crime between America and Japan. The importance of these studies is the
      examination of whether Western-established criminological knowledge is applicable
      to non-Western societies like Japan. Unfortunately, comparative self-report
      studies involving Japan and investigating youth offending are scarce. The current
      study investigates risk factors and self-reports of violence from Osaka and
      Seattle male youths. The findings reveal that Japanese male youths self-report a
      higher prevalence of violence than Seattle male youths. Risk factors for
      violence, issues of comparability, and prevalence versus strength of
      relationships of risk factors are examined. It is concluded that the higher
      prevalence of violence in Osaka is primarily a function of the higher prevalence
      of troubled peers and risk taking. The findings call for replication of this type
      of comparative research. 

PMID- 24013770
TI  - Criminality and the 2D:4D ratio: testing the prenatal androgen hypothesis.
AB  - A decade old theory hypothesizes that brain exposure to androgens promotes
      involvement in criminal behavior. General support for this hypothesis has been
      provided by studies of postpubertal circulating levels of testosterone, at least
      among males. However, the theory also predicts that for both genders, prenatal
      androgens will be positively correlated with persistent offending, an idea for
      which no evidence currently exists. The present study used an indirect measure of
      prenatal androgen exposure-the relative length of the second and fourth fingers
      of the right hand (r2D:4D)-to test the hypothesis that elevated prenatal
      androgens promote criminal tendencies later in life for males and females.
      Questionnaires were administered to 2,059 college students in Malaysia and 1,291
      college students in the United States. Respondents reported their r2D:4D relative
      finger lengths along with involvement in 13 categories of delinquent and criminal
      acts. Statistically significant correlations between the commission of most types
      of offenses and r2D:4D ratios were found for males and females even after
      controlling for age. It is concluded that high exposure to androgens during
      prenatal development contributes to most forms of offending following the onset
      of puberty. 

PMID- 24013771
TI  - From immunosuppression to immunomodulation: current principles and future
      strategies.
AB  - Over the last few decades, tremendous progress has been made in understanding the
      mechanisms of immune responses. This progress has also led to a more detailed
      knowledge of the processes leading to the loss of self-tolerance and the
      destruction of self-tissue in the case of autoimmune diseases, the effector
      mechanism involved in transplant allograft rejection as well as the driving
      factors in exacerbated inflammatory disorders. Despite this progress, the
      challenge still remains to selectively interfere with immune responses
      responsible for autoimmunity or transplant rejection while keeping an intact
      response to infectious agents. To date, such a selective interference is still
      difficult to achieve, as highlighted by the fact that an overall increased risk
      for infections and malignancy continues to be the most frequent side effect of
      the currently used immunosuppressive principles. Nevertheless, although
      discovered several decades ago, many of the 'first-generation' immunosuppressive
      principles such as steroids, methotrexate and cyclosporin A are still in clinical
      use, demonstrating the therapeutic value of these drugs for the patients that are
      in need. In this review, the author describes the mode of action of the currently
      most used immunosuppressive agents (not attempting to cover all principles that
      are available) and expands on recent activities in the discovery and development
      of novel immunomodulatory principles. 

PMID- 24013772
TI  - Differences in the cancer burden among foreign-born and US-born Arab Americans
      living in metropolitan Detroit.
AB  - PURPOSE: Migrant studies often provide clues for cancer etiology. We estimated
      the cancer burden among Arab Americans (ArA) by immigrant status in the
      metropolitan Detroit area, home to one of the highest concentrations of ArA in
      USA. METHODS: A validated name algorithm was used to identify ArA cancer cases
      diagnosed 1990-2009 in the Detroit SEER database. Recorded birthplace was
      supplemented with imputation of nativity using birthdate and social security
      number. Age-adjusted, gender-specific proportional incidence ratios and 95 %
      confidence intervals were calculated comparing all ArA, foreign-born ArA, and US
      born ArA, to non-Hispanic Whites (NHW). RESULTS: Foreign-born ArA males had
      higher proportions of multiple myeloma, leukemia, kidney, liver, stomach, and
      bladder cancer than NHW, while bladder cancer and leukemia were higher among US
      born ArA males. For ArA women, gall bladder and thyroid cancers were
      proportionally higher among both foreign- and US-born compared with NHW. Stomach
      cancer was proportionally higher only among foreign-born women. CONCLUSIONS:
      Cancer proportional incidence patterns among ArA show some similarity to other
      migrant groups, with higher proportional incidences of stomach and liver cancers
      among foreign-born than US-born. Other patterns, such as tobacco-related cancers
      among ArA men and gall bladder and thyroid cancers among ArA women, will require
      more investigation of genetic, epigenetic, and environmental factors.

PMID- 24013773
TI  - Workplace social networks and their relationship with job outcomes and other
      employment characteristics for people with severe mental illness.
AB  - Clients with severe mental illness (SMI) often struggle in their efforts to
      maintain employment. One cause of early job terminations is interpersonal
      difficulties in the workplace. This study explored workplace social networks and
      their relationship with job outcomes and other employment characteristics for
      people with SMI. Results indicated that clients generally had positive
      experiences with both supervisors and coworkers. Contrary to our hypothesis,
      employment model was not associated with better workplace network
      characteristics. Also contrary to our hypothesis, clients employed in group
      placements did not differ in workplace network characteristics from those in
      competitive employment settings. Workplace network characteristics were robustly
      correlated with job satisfaction, but not strongly related to hourly wages or
      overall job tenure. Job tenure at the time of the workplace network assessment
      did show a few modest negative correlations with supervisor and coworker support,
      indicating declining perceived social network support with increasing job tenure.
      Study limitations and future directions for research using this methodology are
      discussed.

PMID- 24013774
TI  - A small peptide with therapeutic potential for inflammatory acne vulgaris.
AB  - A designed peptide named LZ1 with 15 amino acid residues containing strong
      antimicrobial activity against bacteria pathogens of acne vulgaris including
      Propionibacterium acnes, Staphylococcus epidermidis and S. aureus. Especially, it
      exerted strong anti-P. acnes ability. The minimal inhibitory concentration
      against three strains of P. acnes was only 0.6 ug/ml, which is 4 times lower than
      that of clindamycin. In experimental mice skin colonization model, LZ1
      significantly reduced the number of P. acnes colonized on the ear, P. acnes
      induced ear swelling, and inflammatory cell infiltration. It ameliorated
      inflammation induced by P. acnes by inhibiting the secretion of inflammatory
      factors including tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)
      1beta. LZ1 showed little cytotoxicity on human keratinocyte and hemolytic
      activity on human blood red cells. Furthermore, LZ1 was very stable in human
      plasma. Combined with its potential bactericidal and anti-inflammatory
      properties, simple structure and high stability, LZ1 might be an ideal candidate
      for the treatment of acne. 

PMID- 24013776
TI  - Reprogramming and genome integrity: role of non-homologous end joining.

PMID- 24013775
TI  - Rapid copper acquisition by developing murine mesothelioma: decreasing
      bioavailable copper slows tumor growth, normalizes vessels and promotes T cell
      infiltration.
AB  - Copper, an essential trace element acquired through nutrition, is an important co
      factor for pro-angiogenic factors including vascular endothelial growth factor
      (VEGF). Decreasing bioavailable copper has been used as an anti-angiogenic and
      anti-cancer strategy with promising results. However, the role of copper and its
      potential as a therapy in mesothelioma is not yet well understood. Therefore, we
      monitored copper levels in progressing murine mesothelioma tumors and analyzed
      the effects of lowering bioavailable copper. Copper levels in tumors and organs
      were assayed using atomic absorption spectrophotometry. Mesothelioma tumors
      rapidly sequestered copper at early stages of development, the copper was then
      dispersed throughout growing tumor tissues. These data imply that copper uptake
      may play an important role in early tumor development. Lowering bioavailable
      copper using the copper chelators, penicillamine, trientine or
      tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any
      cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody
      therapy. The impact of copper lowering on tumor blood vessels and tumor
      infiltrating T cells was measured using flow cytometry and confocal microscopy.
      Copper lowering was associated with reduced tumor vessel diameter, reduced
      endothelial cell proliferation (reduced Ki67 expression) and lower surface
      ICAM/CD54 expression implying reduced endothelial cell activation, in a process
      similar to endothelial normalization. Copper lowering was also associated with a
      CD4(+) T cell infiltrate. In conclusion, these data suggest copper lowering is a
      potentially useful anti-mesothelioma treatment strategy that slows tumor growth
      to provide a window of opportunity for inclusion of other treatment modalities to
      improve patient outcomes. 

PMID- 24013777
TI  - Hippo signaling: to die or not to die.

PMID- 24013778
TI  - A Bim-activating mould.

PMID- 24013779
TI  - Competition for growth factors: a lot more death with a little less Aktion.

PMID- 24013780
TI  - Cervical pyogenic spinal infections: are they more severe diseases than
      infections in other vertebral locations?
AB  - PURPOSE: Cervical spine pyogenic infections are unusual compared to other
      vertebral segments, but they can be associated to worse clinical outcomes. We
      compared all patients with cervical spine pyogenic infections to those with
      thoracolumbar involvement in terms of epidemiology, prognostic factors and
      clinical outcomes. METHODS: We retrospectively reviewed all patients discharged
      from our institution with diagnosis of pyogenic spinal infections (PSI) during a
      14-year period. Patients' demographics, etiologic agent, co-morbidities, site of
      infection, white blood cell count, erythrocyte sedimentation rate (ESR), C
      reactive protein (CRP) at time of presentation, neurological impairment and
      mortality were registered to compare clinical outcomes of patients with PSI
      affecting the cervical spine and other segments. RESULTS: We studied 102 patients
      with PSI. Nineteen (18.6 %) had cervical involvement; 73.7 % of them were males,
      with a mean age of 65.22 years. 89.7 % of them presented spondylodiscitis; 12
      patients (63.2 %) exhibited a one segment involvement (C5-C6 being the most
      common), and 11 patients presented an epidural abscess. Thirteen patients (68.4
      %) exhibited neurological deficit. Seventeen patients (89.5 %) presented elevated
      ESR and CRP, while 12 patients (63.2 %) exhibited leukocytosis. The causative
      organism was identified in 17 patients (89.5 %). Despite similar baseline
      characteristics, compared to PSI in other locations, patients with cervical PSI
      presented significantly more neurological involvement (68.4 vs. 41 %; p = 0.03),
      they more often required surgical treatment (84.2 vs. 46.3 %; p < 0.01), and they
      had and increased mortality (21.1 % compared to 3.6 %; p = 0.02). CONCLUSION: An
      early diagnosis and prompt treatment should be the goal treating cervical PSI,
      considering the potential devastating complications and increased mortality.

PMID- 24013781
TI  - Nuclear multidrug-resistance related protein 1 contributes to multidrug
      resistance of mucoepidermoid carcinoma mainly via regulating multidrug-resistance
      protein 1: a human mucoepidermoid carcinoma cells model and Spearman's rank
      correlation analysis.
AB  - BACKGROUND: Multidrug resistance-related protein 1 (MRP1/ABCC1) and multidrug
      resistance protein 1 (MDR1/P-glycoprotein/ABCB1) are both membrane-bound drug
      transporters. In contrast to MDR1, MRP1 also transports glutathione (GSH) and
      drugs conjugated to GSH. Due to its extraordinary transport properties,
      MRP1/ABCC1 contributes to several physiological functions and pathophysiological
      incidents. We previously found that nuclear translocation of MRP1 contributes to
      multidrug-resistance (MDR) of mucoepidermoid carcinoma (MEC). The present study
      investigated how MRP1 contributes to MDR in the nuclei of MEC cells. METHODS:
      Western blot and RT-PCR was carried out to investigate the change of multidrug
      resistance protein 1 (MDR1) in MC3/5FU cells after MRP1 was downregulated through
      RNA interference (RNAi). Immunohistochemistry (IHC) staining of 127 cases of MEC
      tissues was scored with the expression index (EI). The EI of MDR1 and MRP1 (or
      nuclear MRP1) was analyzed with Spearman's rank correlation analysis. Using
      multiple tumor tissue assays, the location of MRP1 in other tissues was checked
      by HIC. Luciferase reporter assays of MDR1 promoter was carried out to check the
      connection between MRP1 and MDR1 promoter. RESULTS: MRP1 downregulation led to a
      decreased MDR1 expression in MC3/5FU cells which was caused by decreased activity
      of MDR1 promoter. IHC study of 127 cases of MEC tissues demonstrated a strong
      positive correlation between nuclear MRP1 expression and MDR1 expression.
      Furthermore, IHC study of multiple tumor tissue array sections showed that
      although nuclear MRP1 widely existed in MEC tissues, it was not found in normal
      tissues or other tumor tissues. CONCLUSIONS: Our findings indicate that nuclear
      MRP1 contributes to MDR mainly through regulating MDR1 expression in MEC. And the
      unique location of MRP1 made it an available target in identifying MEC from other
      tumors.

PMID- 24013782
TI  - The CD19 signalling molecule is elevated in NOD mice and controls type 1 diabetes
      development.
AB  - AIMS/HYPOTHESIS: Type 1 diabetes is characterised by early peri-islet insulitis
      and insulin autoantibodies, followed by invasive insulitis and beta cell
      destruction. The immunological events that precipitate invasive insulitis are not
      well understood. We tested the hypothesis that B cells in diabetes-prone NOD mice
      drive invasive insulitis through elevated expression of CD19 and consequent
      enhanced uptake and presentation of beta cell membrane-bound antigens to islet
      invasive T cells. METHODS: CD19 expression and signalling pathways in B cells
      from NOD and control mice were compared. Expansion of CD8(+) T cells specific for
      insulin and islet-specific glucose-6-phosphatase catalytic subunit-related
      protein (IGRP) were compared in CD19-deficient and wild-type NOD mice and this
      was correlated with insulitis severity. The therapeutic potential of anti-CD19
      treatment during the period of T cell activation was assessed for its ability to
      block invasive insulitis. RESULTS: CD19 expression and signalling in B cells was
      increased in NOD mice. CD19 deficiency significantly diminished the expansion of
      CD8(+) T cells with specificity for the membrane-bound beta cell antigen, IGRP.
      Conversely the reduction in CD8(+) T cells with specificity for the soluble beta
      cell antigen, insulin, was relatively small and not significant.
      CONCLUSIONS/INTERPRETATION: Elevated CD19 on NOD B cells promotes presentation of
      the membrane-bound antigen, IGRP, mediating the expansion of autoreactive T cells
      specific for antigens integral to beta cells, which are critical for invasive
      insulitis and diabetes. Downregulating the CD19 signalling pathway in insulin
      autoantibody-positive individuals before the development of type 1 diabetes may
      prevent expansion of islet-invasive T cells and preserve beta cell mass.

PMID- 24013784
TI  - Global Neighborhoods: New Pathways to Diversity and Separation.
AB  - Analyses of neighborhood racial composition in 1980-2000 demonstrate that in
      multiethnic metropolitan regions there is an emerging pathway of change that
      leads to relatively stable integration These are "global neighborhoods" where
      Hispanics and Asians are the pioneer integrators of previously all-white zones,
      later followed by blacks. However, region-wide segregation is maintained at high
      levels by whites' avoidance of all-minority areas and by their continued exodus
      (albeit at reduced levels) from mixed settings. Globalization of neighborhoods
      adds a positive new element of diversity that alters but does not erase the
      traditional dynamic of minority invasion succession.

PMID- 24013783
TI  - Trans-ethnic fine mapping identifies a novel independent locus at the 3' end of
      CDKAL1 and novel variants of several susceptibility loci for type 2 diabetes in a
      Han Chinese population.
AB  - AIMS/HYPOTHESIS: Candidate gene and genome-wide association studies have
      identified ~60 susceptibility loci for type 2 diabetes. A majority of these loci
      have been discovered and tested only in European populations. The aim of this
      study was to assess the presence and extent of trans-ethnic effects of these loci
      in an East Asian population. METHODS: A total of 9,335 unrelated Chinese Han
      individuals, including 4,535 with type 2 diabetes and 4,800 non-diabetic
      ethnically matched controls, were genotyped using the Illumina 200K Metabochip.
      We tested 50 established loci for type 2 diabetes and related traits (fasting
      glucose, fasting insulin, 2 h glucose). Disease association with the additive
      model of inheritance was analysed with logistic regression. RESULTS: We found
      that 14 loci significantly transferred to the Chinese population, with two loci
      (p = 5.7 * 10(-12) for KCNQ1; p = 5.0 * 10(-8) for CDKN2A/B-CDKN2BAS) reaching
      independent genome-wide statistical significance. Five of these 14 loci had
      similar lead single-nucleotide polymorphisms (SNPs) as were found in the European
      studies while the other nine were different. Further stepwise conditional
      analysis identified a total of seven secondary signals and an independent novel
      locus at the 3' end of CDKAL1. CONCLUSIONS/INTERPRETATION: These results suggest
      that many loci associated with type 2 diabetes are commonly shared between
      European and Chinese populations. Identification of population-specific SNPs may
      increase our understanding of the genetic architecture underlying type 2 diabetes
      in different ethnic populations.

PMID- 24013785
TI  - Slithering toward clarity: snakes shed new light on the evolution and function of
      sex chromosomes.

PMID- 24013787
TI  - Super-thermostable platinum nanoparticles on fluorinated clay.
AB  - Pt/fluorinated clay nanocomposites were prepared by clay-mediated in situ
      reduction; these nanocomposites demonstrated ultrahigh Pt nanoparticle thermal
      stability (up to 1000  degrees C), large BET surface area (379 m(2) g(-1)),
      uniform dispersion in aqueous media, and intriguing catalytic properties. 

PMID- 24013786
TI  - Expression of HAb18G in non-small lung cancer and characterization of activation,
      migration, proliferation, and apoptosis in A549 cells following siRNA-induced
      downregulation of HAb18G.
AB  - HAb18G, a novel cancer biomarker, has been shown to be involved in the
      progression of malignancy by regulating expression of vascular endothelial growth
      factor (VEGF) and matrixmetalloproteinases (MMPs). The goal of this study was to
      evaluate the role of HAb18G in the biology of NSCLC and to determine its
      potential as a therapeutic target. HAb18G protein expression was detected by
      immunohistochemistry in 150 NSCLC tissues. The results showed that HAb18G protein
      expression was associated with tumor diameter, lymph node status, tumor stage,
      and poor prognosis (P < 0.05). Multivariate analysis showed that HAb18G
      overexpression was an independent prognostic factor (HR, 3.713; 95 % CI, 1.114
      12.373; P = 0.033). Transient infection of A549 lung cancer cells with small
      interfering RNA (SiRNA) against HAb18G efficiently inhibited the expression of
      HAb18G in A549 lung cancer cells at both mRNA and protein levels. Downregulation
      of HAb18G not only reduced MMP-2, MMP-9, and VEGF at mRNA and protein levels in
      A549 cells, but also inhibited fibroblasts to secrete MMP-2 and MMP-9 at mRNA
      level. Additionally, downregulation of HAb18G mRNA resulted in decreased
      migration, proliferation, and increased apoptosis of A549 in vitro. Our findings
      suggest that HAb18G overexpression plays an important role in progression of
      NSCLC and HAb18G may be a potential target of NSCLC therapy.

PMID- 24013788
TI  - Integration of visual and inertial cues in the perception of angular self-motion.
AB  - The brain is able to determine angular self-motion from visual, vestibular, and
      kinesthetic information. There is compelling evidence that both humans and non
      human primates integrate visual and inertial (i.e., vestibular and kinesthetic)
      information in a statistically optimal fashion when discriminating heading
      direction. In the present study, we investigated whether the brain also
      integrates information about angular self-motion in a similar manner. Eight
      participants performed a 2IFC task in which they discriminated yaw-rotations (2-s
      sinusoidal acceleration) on peak velocity. Just-noticeable differences (JNDs)
      were determined as a measure of precision in unimodal inertial-only and visual
      only trials, as well as in bimodal visual-inertial trials. The visual stimulus
      was a moving stripe pattern, synchronized with the inertial motion. Peak velocity
      of comparison stimuli was varied relative to the standard stimulus. Individual
      analyses showed that data of three participants showed an increase in bimodal
      precision, consistent with the optimal integration model; while data from the
      other participants did not conform to maximum-likelihood integration schemes. We
      suggest that either the sensory cues were not perceived as congruent, that
      integration might be achieved with fixed weights, or that estimates of visual
      precision obtained from non-moving observers do not accurately reflect visual
      precision during self-motion.

PMID- 24013789
TI  - The effect of haptic guidance and visual feedback on learning a complex tennis
      task.
AB  - While haptic guidance can improve ongoing performance of a motor task, several
      studies have found that it ultimately impairs motor learning. However, some
      recent studies suggest that the haptic demonstration of optimal timing, rather
      than movement magnitude, enhances learning in subjects trained with haptic
      guidance. Timing of an action plays a crucial role in the proper accomplishment
      of many motor skills, such as hitting a moving object (discrete timing task) or
      learning a velocity profile (time-critical tracking task). The aim of the present
      study is to evaluate which feedback conditions-visual or haptic guidance-optimize
      learning of the discrete and continuous elements of a timing task. The experiment
      consisted in performing a fast tennis forehand stroke in a virtual environment. A
      tendon-based parallel robot connected to the end of a racket was used to apply
      haptic guidance during training. In two different experiments, we evaluated which
      feedback condition was more adequate for learning: (1) a time-dependent discrete
      task-learning to start a tennis stroke and (2) a tracking task-learning to follow
      a velocity profile. The effect that the task difficulty and subject's initial
      skill level have on the selection of the optimal training condition was further
      evaluated. Results showed that the training condition that maximizes learning of
      the discrete time-dependent motor task depends on the subjects' initial skill
      level. Haptic guidance was especially suitable for less-skilled subjects and in
      especially difficult discrete tasks, while visual feedback seems to benefit more
      skilled subjects. Additionally, haptic guidance seemed to promote learning in a
      time-critical tracking task, while visual feedback tended to deteriorate the
      performance independently of the task difficulty and subjects' initial skill
      level. Haptic guidance outperformed visual feedback, although additional studies
      are needed to further analyze the effect of other types of feedback visualization
      on motor learning of time-critical tasks. 

PMID- 24013790
TI  - Performance of the Towers of Hanoi task and cortical electroencephalographic
      power changes associated with infancy, adolescence, and early adulthood.
AB  - The executive functions, which depend on the adequate maturation and functioning
      of the prefrontal cortex and its connection to posterior zones, follow a process
      of development as age increases. This work studied changes in the absolute power
      (AP) of EEG activity recorded in the prefrontal and parietal areas during the
      performance of the Tower of Hanoi task in children, adolescents, and young
      adults. Three groups of healthy male subjects such as G1, 11-13; G2, 18-20; and
      G3, 26-30, years of age were recorded at the F3, F4, P3, and P4 derivations under
      two conditions: basal and performance of the Towers of Hanoi task. The majority
      of subjects in G1 failed to complete the task in the allotted time (7 min), while
      those in G2 and G3 were able to resolve the task quickly and efficiently. During
      the Towers of Hanoi task, G1 showed an increase of AP in the delta band only in
      the frontal areas, with a decrease in the alpha1 and alpha2 sub-bands only at the
      parietal derivations, while G2 and G3 were characterized by an increase of AP in
      the delta band and a decreased AP in the alpha1 and alpha2 sub-bands in all
      derivations. These data demonstrate that during the performance of the Towers of
      Hanoi task, the prefrontal and parietal areas show a characteristic EEG pattern
      in relation to age. It is probable that the AP patterns obtained in G2 and G3 are
      associated with the functional changes at cortical levels that adolescents and
      early adults require to achieve an adequate and fast performance of the Towers of
      Hanoi task. 

PMID- 24013791
TI  - Locally enhanced conductivity due to the tetragonal domain structure in
      LaAlO3/SrTiO3 heterointerfaces.
AB  - The ability to control materials properties through interface engineering is
      demonstrated by the appearance of conductivity at the interface of certain
      insulators, most famously the {001} interface of the band insulators LaAlO3 and
      TiO2-terminated SrTiO3 (STO; refs 1, 2). Transport and other measurements in this
      system show a plethora of diverse physical phenomena. To better understand the
      interface conductivity, we used scanning superconducting quantum interference
      device microscopy to image the magnetic field locally generated by current in an
      interface. At low temperature, we found that the current flowed in conductive
      narrow paths oriented along the crystallographic axes, embedded in a less
      conductive background. The configuration of these paths changed on thermal
      cycling above the STO cubic-to-tetragonal structural transition temperature,
      implying that the local conductivity is strongly modified by the STO tetragonal
      domain structure. The interplay between substrate domains and the interface
      provides an additional mechanism for understanding and controlling the behaviour
      of heterostructures.

PMID- 24013792
TI  - Selection of reliable reference genes for quantitative real-time polymerase chain
      reaction studies in maize grains.
AB  - KEY MESSAGE: The stability of candidate reference genes was evaluated in maize
      landrace varieties and during multiple grain developmental stages to evaluate the
      expression of carotenoid-related genes by RT-qPCR for application to maize
      biofortification. Vitamin A deficiency affects millions of children worldwide;
      therefore, increasing the content of vitamin A precursors in maize grains is of
      interest. The study of the expression of genes involved in the carotenoid
      biosynthetic pathway in maize grains has provided useful information for
      metabolic engineering approaches. However, reliable results using real-time
      quantitative polymerase chain reaction (RT-qPCR) experiments are dependent on the
      use of the appropriate reference genes. In this study, we utilized geNorm and
      NormFinder softwares to identify the most stably expressed candidate reference
      genes in samples from seven stages of grain development and from eight landrace
      varieties. The results of the analysis performed using geNorm indicated that
      tubulin (TUB) and actin (ACT) were the most suitable reference genes among all
      experimental conditions, while glyceraldehyde-3-phosphate dehydrogenase gene
      (GAPDH) showed the least stability. The same result was obtained with the
      NormFinder software. The minimum number of genes required in each experimental
      condition to normalize the gene expression data was also determined by geNorm.
      The expression of phytoene synthase gene (PSY1), the first enzyme in the
      carotenoid biosynthetic pathway, was overestimated when the least stable
      candidate gene (GAPDH) was used as the internal control instead of the most
      stable gene pair (ACT + TUB), thus highlighting the importance of validating
      reference genes before conducting a RT-qPCR experiment to obtain accurate
      results. This study is the first survey of the stability of genes for use as
      reference genes to normalize RT-qPCR data from maize landraces during multiple
      stages of grain development.

PMID- 24013793
TI  - The phytochrome gene family in soybean and a dominant negative effect of a
      soybean PHYA transgene on endogenous Arabidopsis PHYA.
AB  - KEY MESSAGE: The evolutionary origin of the phytochrome genes in soybean was
      analyzed. The expression profiles of PHYA paralogs were characterized. The
      heterologous expression of GmPHYA1 in Arabidopsis resulted in longer hypocotyls.
      The phytochromes (PHY) are a small family of red/far-red light photoreceptors
      which regulate a number of important developmental responses in plants. So far,
      the members of the PHY gene family in soybean (Glycine max) remain unclear and an
      understanding of each member's physiological functions is limited. Our present in
      silico analysis revealed that the soybean genome harbors four PHYA, two PHYB and
      two PHYE, totally four pairs of eight PHY loci. The phylogenetic analysis
      suggested that the four PHY paralogous pairs originated from the latest round of
      genome duplication (~13 million years ago) and the four copies of PHYA were
      remnants of the two rounds of genome duplication (~58 and ~13 million years ago).
      A possible evolutionary history of PHYA homologs in the three legume species
      (soybean, Medicago truncatula, and Lotus japonicus) was proposed and the fate of
      duplicate soybean PHYA genes following polyploidization was discussed. The
      expression profiles of a soybean PHYA paralogous pair (GmPHYA1 and GmPHYA2)
      showed that the transcript abundance was highest in the aerial organs of young
      plants. The physiological role of GmPHYA1 was explored by observing the de
      etiolation phenotype of transgenic Arabidopsis plants constitutively expressing
      GmPHYA1. The GmPHYA1 protein interfered with the function of endogenous PHYA with
      respect to de-etiolation in a dominant negative manner when exogenously expressed
      in Arabidopsis. The elucidation of the PHY gene family members in soybean provide
      us with a general description and understanding of the photoreceptor gene family
      in this important crop plant.

PMID- 24013796
TI  - Predicting through-focus visual acuity with the eye's natural aberrations.
AB  - PURPOSE: To develop a predictive optical modeling process that utilizes
      individual computer eye models along with a novel through-focus image quality
      metric. METHODS: Individual eye models were implemented in optical design
      software (Zemax, Bellevue, WA) based on evaluation of ocular aberrations, pupil
      diameter, visual acuity, and accommodative response of 90 subjects (180 eyes; 24
      63 years of age). Monocular high-contrast minimum angle of resolution (logMAR)
      acuity was assessed at 6 m, 2 m, 1 m, 67 cm, 50 cm, 40 cm, 33 cm, 28 cm, and 25
      cm. While the subject fixated on the lowest readable line of acuity, total ocular
      aberrations and pupil diameter were measured three times each using the Complete
      Ophthalmic Analysis System (COAS HD VR) at each distance. A subset of 64 mature
      presbyopic eyes was used to predict the clinical logMAR acuity performance of
      five novel multifocal contact lens designs. To validate predictability of the
      design process, designs were manufactured and tested clinically on a population
      of 24 mature presbyopes (having at least +1.50 D spectacle add at 40 cm). Seven
      object distances were used in the validation study (6 m, 2 m, 1 m, 67 cm, 50 cm,
      40 cm, and 25 cm) to measure monocular high-contrast logMAR acuity. RESULTS:
      Baseline clinical through-focus logMAR was shown to correlate highly (R2 = 0.85)
      with predicted logMAR from individual eye models. At all object distances, each
      of the five multifocal lenses showed less than one line difference, on average,
      between predicted and clinical normalized logMAR acuity. Correlation showed R2
      between 0.90 and 0.97 for all multifocal designs. CONCLUSIONS: Computer-based
      models that account for patient's aberrations, pupil diameter changes, and
      accommodative amplitude can be used to predict the performance of contact lens
      designs. With this high correlation (R2 >= 0.90) and high level of
      predictability, more design options can be explored in the computer to optimize
      performance before a lens is manufactured and tested clinically.

PMID- 24013794
TI  - Wheat gene TaS3 contributes to powdery mildew susceptibility.
AB  - KEY MESSAGE: Identification of TaS3 as a potential susceptibility gene encoding a
      protein homologous to ULP1 protease in wheat, which may regulate SUMO function
      facilitating powdery mildew attack. Some plant genes that are required for
      susceptibilities to certain pathogens are known as susceptibility genes or
      susceptibility factors, whose loss-of-function mutations can confer the plants
      resistances. To identify potential susceptibility genes to powdery mildew in
      wheat, differentially expressed genes in compatible and incompatible interactions
      between wheat and powdery mildew were examined by the cDNA chip assay. The genes
      exclusively expressed in the susceptible cultivar were interfered using biolistic
      transient transformation in wheat epidermal cells. The suppression of gene TaS3
      (Triticum aestivum susceptibility) decreased the pathogen penetration by 19%, and
      its over-expression increased the disease susceptibility. The deduced protein
      from TaS3 belongs to the putative ubiquitin-like protease 1 peptidase domain
      family. Subcellular localization studies revealed that its protein was
      accumulated in the nucleus. Quantitative real-time polymerase chain reaction
      analysis revealed that TaS3 transcript was significantly induced in the
      compatible host. This suggests that TaS3 is a potential susceptible gene and its
      function may be related to regulate SUMO functions.

PMID- 24013795
TI  - A genome-wide identification and characterization of mircoRNAs and their targets
      in 'Suli' pear (Pyrus pyrifolia white pear group).
AB  - MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that are
      endogenous regulators of gene expression. miRNAs play a crucial role in cells via
      degradation of target mRNAs or by inhibition of target protein translation. In
      the present study, 186 new potentially conserved pear miRNAs belonging to 37
      families were identified. The length of mature miRNAs ranged from 19 to 24 nt,
      and most of the miRNAs (154 out of 186) were 21 nt in length. The length of pre
      miRNAs in pear was also found to vary from 62 to 282 nt with an average of 105 +/
      43 nt. The potential miRNAs belonged to 29 clusters involving 20 different miRNA
      families. Using these potential miRNAs, we further scoured of the pear genome and
      found 326 potential target genes, which included transcription factors, stress
      responsive genes, and the genes involved in transmembrane transport and signal
      transduction. Gene ontology analysis of these potential targets suggested that 47
      biological processes were potentially regulated by miRNAs, including oxidation
      reduction, stress response, transport, etc. KEGG pathway analysis showed that the
      identified miRNAs were found in 15 metabolism networks which were related to
      starch and sucrose metabolism, and ascorbate and aldarate metabolism, among
      others. Our study will help in the further understanding of the essential role of
      miRNAs in growth and development and stress response of pear.

PMID- 24013797
TI  - Factors that influence in vitro cholesterol deposition on contact lenses.
AB  - PURPOSE: The purpose of this study was to analyze the impact that incubation
      time, lipid concentration, and solution replenishment have on silicone hydrogel
      (SiHy) and conventional hydrogel (CH) contact lens cholesterol deposition via in
      vitro radiochemical experiments. METHODS: Four SiHy (senofilcon A, lotrafilcon B,
      comfilcon A, balafilcon A) and two CH (etafilcon A and omafilcon A) contact
      lenses were incubated in an artificial tear solution (ATS) that contained major
      tear film proteins, lipids, salts, salts, and a trace amount of radioactive C
      cholesterol. Lenses were incubated for various incubation times (1, 3, 7, 14, or
      28 days), with three concentrations of lipid (0.5*, 1*, 2* tear film
      concentration) and with or without solution replenishment to assess each
      variable's impact on cholesterol deposition. After incubation, the lenses were
      extracted using 2:1 chloroform:methanol, extracts were analyzed in a beta counter
      and masses (micrograms per lens) were extrapolated from standard curves. RESULTS:
      Within the SiHy materials, balafilcon A deposited the greatest amount of
      cholesterol (p < 0.001) and lotrafilcon B the lowest (p < 0.001). The CH lens
      materials showed significantly lower uptake amounts than any of the SiHy lens
      materials (p < 0.001). The uptake of cholesterol ranged from 0.01 +/- 0.01
      MUg/lens to 3.22 +/- 0.34 MUg/lens for all lens materials. Kinetic uptake of
      cholesterol was shown to be continuous throughout the 28 days of incubation
      without plateau (p < 0.001), and varying the lipid concentration did impact the
      resulting cholesterol deposition (p < 0.001). Replenishing the ATS every other
      day also affected cholesterol deposition throughout the experiment. Overall, the
      deposition pattern was 2* > replenishing > 1* > 0.5*. CONCLUSIONS: Overall, SiHy
      lenses deposit significantly more cholesterol than CH lens materials, and the
      mass of lipid deposited is dependent on the contact lens material, length of
      incubation, concentration of lipids in the ATS, and the replenishment of ATS.

PMID- 24013798
TI  - Widowed mothers' coresidence with adult children.
AB  - OBJECTIVES: Coresidence is one way that middle-aged offspring assist vulnerable,
      aging parents. This study investigated which characteristics of widowed mothers
      and adult children predict coresidence. When coresidence occurred, the analysis
      explored how individual children's characteristics were associated with their
      coresidence with the mother. METHOD: Survey data from adults 53-54 years old in
      1993 (N = 2,324) and a random sibling reported about their living situation,
      other siblings, and their mother, median age 80. RESULTS: Logistic regressions
      revealed that mothers in poor health, who were older, and who had a daughter were
      more likely to live with a child. Among coresiding families, results from
      discrete choice conditional logit models showed that widowed mothers were more
      likely to live with an unmarried son than an unmarried daughter. Married children
      were less likely to coreside than unmarried children, but married daughters were
      more likely than married sons to coreside. Past receipt of financial help from
      parents was not associated with coresidence. Coresidence was more likely for
      those with a close relationship with the mother. DISCUSSION: The discussion
      considers coresidence as an intergenerational transfer and its importance for the
      contemporary aging society. Data are needed on characteristics of all offspring
      to test theories about parent-child relationships.

PMID- 24013799
TI  - Age differences in wisdom-related knowledge: does the age relevance of the task
      matter?
AB  - OBJECTIVES: Contrary to lay theories, past work does not suggest robust age
      differences in wisdom-related knowledge across the adult life span. This study
      investigated a potential moderator of age differences in wisdom-related
      knowledge: The age relevance of a given wisdom task. METHOD: To test this
      moderator, 192 participants covering the adult life span were asked to think
      aloud about a traditional vignette-based wisdom task with no particular age
      relevance and about newly developed tasks of problems that arguably are
      particularly salient in young adulthood, namely, marital conflicts. These tasks
      were presented as vignette and as naturalistic video clips. RESULTS: Replicating
      earlier work, there were no linear age differences in wisdom-related knowledge as
      elicited by the traditional age-neutral wisdom task. However, both vignette-based
      and video-based tasks about marital conflict elicited greater wisdom-related
      knowledge in younger than in older adults. Young adults' greater actual
      experience and openness to marital conflict contributed to these age differences.
      DISCUSSION: This study provides evidence for the idea that age differences in
      wise reasoning about fundamental life issues depend on the relevance of age
      normative problems in individuals' own lives. This suggests that any phase of
      life offers opportunities for the attainment of wisdom-related strengths as long
      as an individual is willing and able to actively engage in life's ongoing
      challenges.

PMID- 24013800
TI  - Strategies and factors that help or hinder memory.

PMID- 24013801
TI  - Ageism and body esteem: associations with psychological well-being among late
      middle-aged African American and European American women.
AB  - OBJECTIVES: Social expectancy theory posits that cultural values shape how
      individuals perceive and evaluate others, and this influences how others evaluate
      themselves. Based on this theory, ageism may shape older individuals' self
      evaluations. Given the cultural focus on beauty and youth, perceptions of age
      discrimination may be associated with lower body esteem, and this may be
      associated with poor psychological well-being. Because discrimination has been
      associated with poor health, and perceptions of health can affect body
      perceptions, subjective health status may also contribute to lower body esteem.
      METHOD: These associations are assessed in a structural equation model for 244
      African American and European American women in their early 60s. RESULTS:
      Perceptions of age discrimination and body esteem were associated with lower
      psychological well-being for both ethnic groups. Body esteem partially mediated
      the association between age discrimination and psychological well-being among
      European American women but not among African American women. DISCUSSION: Age
      related discrimination is one source of psychological distress for older adults,
      though ageism's associations with body esteem, health, and psychological well
      being vary significantly for European American and African American women.
      Examining body perceptions and health in the contexts of ageism and ethnicity is
      necessary when considering the psychological well-being of older women.

PMID- 24013803
TI  - Apoptotic colonopathy under immunosuppression: mycophenolate-related effects and
      beyond.
AB  - BACKGROUND/AIMS: Diarrhea developing in patients under immunosuppression has a
      variety of underlying causes. A broad spectrum of histological findings can be
      found in intestinal biopsies taken for the diagnostic workup of diarrhea
      including a pathologically increased proportion of epithelial cell apoptosis in
      the colon, for which the descriptive term 'apoptotic colonopathy' was coined. In
      recent years, the immunosuppressive drug mycophenolate (mycophenolic acid, MPA)
      has been identified as a prototypical cause of apoptotic colonopathy, but other
      conditions may show similar or overlapping histological pictures. METHODS: Cases
      of likely or possible MPA colonopathy (n = 18) were retrospectively identified
      from the archive files. Clinical information on patient history, clinical
      presentation and endoscopic findings were recorded. All cases were routinely
      processed, i.e. stained by hematoxylin and eosin (HE) stain, optionally
      supplemented by special histochemical and immune stains. RESULTS AND CONCLUSION:
      Histopathological hallmarks of MPA treatment-related changes in the colon mucosa
      are reviewed with respect to the major histopathological differential diagnoses
      including normal and near-normal findings, infectious diseases, graft-versus-host
      disease and inflammatory bowel diseases. Furthermore, the challenge of multiple
      concomitant pathologies while on MPA treatment, in particular infectious
      diseases, is discussed, and some open questions concerning the effects of MPA on
      colon pathology are pointed out.

PMID- 24013802
TI  - Stimulus-frequency otoacoustic emission suppression tuning in humans: comparison
      to behavioral tuning.
AB  - As shown by the work of Kemp and Chum in 1980, stimulus-frequency otoacoustic
      emission suppression tuning curves (SFOAE STCs) have potential to objectively
      estimate behaviorally measured tuning curves. To date, this potential has not
      been tested. This study aims to do so by comparing SFOAE STCs and behavioral
      measures of tuning (simultaneous masking psychophysical tuning curves, PTCs) in
      10 normal-hearing listeners for frequency ranges centered around 1,000 and 4,000
      Hz at low probe levels. Additionally, SFOAE STCs were collected for varying
      conditions (probe level and suppression criterion) to identify the optimal
      parameters for comparison with behavioral data and to evaluate how these
      conditions affect the features of SFOAE STCs. SFOAE STCs qualitatively resembled
      PTCs: they demonstrated band-pass characteristics and asymmetric shapes with
      steeper high-frequency sides than low, but unlike PTCs they were consistently
      tuned to frequencies just above the probe frequency. When averaged across
      subjects the shapes of SFOAE STCs and PTCs showed agreement for most recording
      conditions, suggesting that PTCs are predominantly shaped by the frequency
      selective filtering and suppressive effects of the cochlea. Individual SFOAE STCs
      often demonstrated irregular shapes (e.g., "double-tips"), particularly for the
      1,000-Hz probe, which were not observed for the same subject's PTC. These results
      show the limited utility of SFOAE STCs to assess tuning in an individual. The
      irregularly shaped SFOAE STCs may be attributed to contributions from SFOAE
      sources distributed over a region of the basilar membrane extending beyond the
      probe characteristic place, as suggested by a repeatable pattern of SFOAE
      residual phase shifts observed in individual data. 

PMID- 24013805
TI  - Macrophage activation syndrome.

PMID- 24013804
TI  - Docosahexaenoic acid supplementation alters key properties of cardiac
      mitochondria and modestly attenuates development of left ventricular dysfunction
      in pressure overload-induced heart failure.
AB  - PURPOSE: Supplementation with the n3 polyunsaturated fatty acid docosahexaenoic
      acid (DHA) is beneficial in heart failure patients, however the mechanisms are
      unclear. DHA is incorporated into membrane phospholipids, which may prevent
      mitochondrial dysfunction. Thus we assessed the effects of DHA supplementation on
      cardiac mitochondria and the development of heart failure caused by aortic
      pressure overload. METHODS: Pathological cardiac hypertrophy was generated in
      rats by thoracic aortic constriction. Animals were fed either a standard diet or
      were supplemented with DHA (2.3 % of energy intake). RESULTS: After 14 weeks,
      heart failure was evident by left ventricular hypertrophy and chamber enlargement
      compared to shams. Left ventricle fractional shortening was unaffected by DHA
      treatment in sham animals (44.1 +/- 1.6 % vs. 43.5 +/- 2.2 % for standard diet
      and DHA, respectively), and decreased with heart failure in both treatment
      groups, but to a lesser extent in DHA treated animals (34.9 +/- 1.7 %) than with
      the standard diet (29.7 +/- 1.5 %, P < 0.03). DHA supplementation increased DHA
      content in mitochondrial phospholipids and decreased membrane viscosity.
      Myocardial mitochondrial oxidative capacity was decreased by heart failure and
      unaffected by DHA. DHA treatment enhanced Ca(2+) uptake by subsarcolemmal
      mitochondria in both sham and heart failure groups. Further, DHA lessened Ca(2+)
      induced mitochondria swelling, an index of permeability transition, in heart
      failure animals. Heart failure increased hydrogen peroxide-induced mitochondrial
      permeability transition compared to sham, which was partially attenuated in
      interfibrillar mitochondria by treatment with DHA. CONCLUSIONS: DHA decreased
      mitochondrial membrane viscosity and accelerated Ca(2+) uptake, and attenuated
      susceptibility to mitochondrial permeability transition and development of left
      ventricular dysfunction.

PMID- 24013806
TI  - Synthesis of biaryl imino/keto carboxylic acids via aryl amide directed C-H
      activation reaction.
AB  - A novel Pd-catalysed C-H activation reaction for the synthesis of biaryl
      imino/keto carboxylic acids is developed. This reaction underwent aryl amide
      directed C-H activation ortho-acylation followed by ring closing and ring opening
      processes to give a range of biaryl imino/keto carboxylic acids. Our methodology
      features the utilization of a cheap and green oxidant (TBHP) as well as readily
      available aldehydes. 

PMID- 24013807
TI  - Predicting a biliary aetiology in paediatric acute pancreatitis.
AB  - OBJECTIVE: Acute biliary pancreatitis (ABP) is a common cause of pancreatitis
      which may require timely intervention. We aimed to identify routine laboratory
      parameters for early prediction of biliary aetiology in paediatric acute
      pancreatitis (AP). DESIGN: A retrospective review of children with AP (January
      2000-July 2011) was performed at two tertiary paediatric hospitals in New South
      Wales, Australia. Predictors of ABP using laboratory parameters (measured within
      48 h of presentation) were determined using a multivariate logistic regression
      model and evaluated. RESULTS: Of the 131 pancreatitis episodes reviewed, 21 (16%)
      were biliary-related. Raised serum lipase, alkaline phosphatase, gamma-glutamyl
      transpeptidase (GGT), alanine aminotransferase (ALT) and aspartate
      aminotransferase were associated with biliary aetiology (all p<0.0016) on
      univariate analysis. In multiple logistic regression, serum GGT >=40 U/L, ALT
      >=150 U/L, and lipase >=15 * the upper limit of normal (ULN) were predictive of
      ABP. To improve clinical applicability, the predictive performance when at least
      two of the three ABP predictors (coined the 'biliary pancreatitis triad') were
      satisfied was evaluated. The triad performed with a specificity, sensitivity,
      positive predictive value and negative predictive value of 95, 89, 76 and 98%,
      respectively. CONCLUSIONS: The biliary pancreatitis triad of serum GGT >=40 U/L,
      ALT >=150 U/L and lipase >=15*ULN within 48 h of presentation may be used as
      simple clinical predictors of ABP in children. Children with values falling below
      2 or 3 of these thresholds are very unlikely to have AP due to a biliary cause.

PMID- 24013808
TI  - Suicide and accidental deaths in children and adolescents in England and Wales,
      2001-2010.
AB  - OBJECTIVES: To investigate the impact of narrative verdicts on suicide statistics
      among 10-19-year-olds; to identify the number and rate of suicide and accidental
      deaths, particularly in 10-14-year-olds. DESIGN: National cohort study. SETTING:
      England and Wales. METHODS: Mid-year population estimates from the Office for
      National Statistics (ONS) were used to calculate rates per 100,000 population for
      suicide (undetermined and suicide verdicts) and accidental deaths (poisoning,
      hanging) for those aged 10-14 and 15-19. Trends in rates over time (2001-2010)
      were investigated using Poisson regression. Interaction tests were carried out to
      determine differences in trends between the two time periods (2001-2005 and 2006
      2010). RESULTS: There were 1523 suicides (2.25/100,000). Suicide rates were
      highest in those aged 15-19 years (4.04/100,000) and in males (3.14/100,000).
      Between 2001 and 2010, rates significantly decreased among those aged 15-19 years
      (incidence rate-ratio (IRR): 0.95; 95% CI 0.93 to 0.97), with no change in rates
      of accidental deaths (IRR: 1.01, 95% CI 0.95 to 1.07). However, there was a
      significant interaction between the two time periods for accidental poisonings
      (2001-2005: IRR: 0.79 (95% CI 0.69 to 0.91); 2006-2010: IRR: 1.01 (95% CI 0.89 to
      1.15), interaction p=0.012) and accidental hangings (2001-2005: IRR: 0.93 (95% CI
      0.76 to 1.14); 2006-2010: IRR: 1.25 (95% CI 1.04 to 1.49), interaction=0.01)
      Undetermined deaths significantly decreased among females aged 15-19 yeras (IRR:
      0.93; 95% CI 0.88 to 0.98). There were no significant trends among 10-14-year
      olds. CONCLUSIONS: Rates of suicide are higher among older adolescents and males.
      There was a significant fall in suicide rates in males aged 15-19 years that was
      not accounted for by changes in rates of accidental death. The absence of a
      significant trend in suicide or accidental deaths in those aged 10-14 years may
      have been the result of small numbers. However, monitoring should continue to
      identify longitudinal trends in all young people.

PMID- 24013809
TI  - Laparoscopic adjustable gastric banded plication: evolution of procedure and 2
      year results.
AB  - BACKGROUND: Laparoscopic adjustable gastric banded plication (LAGBP) is a new
      restrictive bariatric procedure combining adjustable banding and greater
      curvature plication of the stomach. This study aimed to report the evolution of
      this surgical technique and analyze the surgical results. METHODS: Eighty
      patients who underwent LAGBP were enrolled in this study. The band-first
      technique was used in 50 patients from May 2009 to June 2011 and was then changed
      to the plication-first technique from July 2011 to October 2011. Patients'
      demographics and pre- and postoperative data, including complications and weight
      loss, were collected and analyzed. RESULTS: Eighty patients (26 men and 54 women)
      with a mean age of 30.75 +/- 8.68 years and a mean body mass index of 38.05 +/-
      4.73 kg/m2 were evaluated with a mean follow-up of 10.52 (1-24) months. The
      average operation duration and hospital stay were 92.85 +/- 35.86 min and 1.73 +/
      1.04 days, respectively. No intraoperative complications or surgical mortality
      was observed in this series. Four (8%) postoperative complications occurred with
      the band-first technique and one (3%) with the plication-first technique. Mean
      excess weight loss (percentage) at 6, 12, 18, and 24 months were 42.59 +/- 13.67,
      56.38 +/- 19.89, 57.59 +/- 19.88, and 65.84 +/- 17.36%, respectively. The
      frequency of band adjustment was 2.44 +/- 2.21 times in 2 years. CONCLUSIONS: In
      this present 2-year result, LAGBP using plication-first technique revealed fewer
      complications and good weight loss. Longer follow-up is still necessary to be
      accepted as a stand-alone bariatric procedure.

PMID- 24013810
TI  - Profiling solute carrier transporters in the human blood-brain barrier.
AB  - The neuroprotective function of the blood-brain barrier (BBB) presents a major
      challenge for drug delivery to the central nervous system (CNS). Critical to this
      function, BBB membrane transporters include the ATP-binding cassette (ABC)
      transporters, which limit drug penetration across the BBB, and the less-well
      studied solute carrier (SLC) transporters. In this work, expression profiling of
      359 SLC transporters, comparative expression analysis with kidney and liver, and
      immunoassays in brain microvessels (BMVs) identified previously unknown
      transporters at the human BBB. 

PMID- 24013811
TI  - Clinical nanomedicine: a solution to the chemotherapy conundrum in pediatric
      leukemia therapy.
AB  - Although chemotherapy-based treatment of leukemia has tremendously improved
      survival rates in children, induction of treatment-related side effects is a
      major concern in clinical oncology. The development of nanotechnology-based drug
      delivery techniques to target clinically approved anticancer agents specifically
      to leukemic cells should diminish toxic side effects. This review aims to address
      the rational design of nanotherapeutics in treating hematologic malignancies with
      a focus on acute lymphoblastic leukemia (ALL)--the most prominent form of
      pediatric cancer.

PMID- 24013812
TI  - Freehand 'figure 4' technique for tibial intramedullary nailing: introduction of
      technique and review of 87 cases.
AB  - Intramedullary nailing of tibial fractures is commonplace, and freehand operative
      techniques are increasingly popular. The standard freehand method has the knee of
      the injured leg flexed over a radiolucent bolster. This requires the theatre
      fluoroscope to swing from antero-posterior to lateral position several times.
      Furthermore, guide wire placement, reaming and nail insertion are all performed
      well above most surgeons' shoulder height. Alternatively the leg is hung over the
      edge of the table, and the assistant must crouch and hold the leg until the nail
      is passed beyond the fracture. We describe a freehand figure 4 position technique
      for tibial nailing which is easier both for the surgeons and the radiographer,
      and present a series of 87 consecutive cases utilising this method.

PMID- 24013813
TI  - Three-column classification and Schatzker classification: a three- and two
      dimensional computed tomography characterisation and analysis of tibial plateau
      fractures.
AB  - OBJECTIVE: The aim of the study was to evaluate inter-observer reliability and
      intra-observer reproducibility between the three-column classification and
      Schatzker classification systems using 2D and 3D CT models. MATERIALS AND
      METHODS: Fifty-two consecutive patients with tibial plateau fractures were
      evaluated by five orthopaedic surgeons. All patients were classified into
      Schatzker and three-column classification systems using x-rays and 2D and 3D CT
      images. The inter-observer reliability was evaluated in the first round and the
      intra-observer reliability was determined during the second round 2 weeks later.
      RESULTS: The average intra-observer reproducibility for the three-column
      classification was from substantial to excellent in all sub classifications, as
      compared with Schatzker classification. The inter-observer kappa values increased
      from substantial to excellent in three-column classification and to moderate in
      Schatzker classification The average values for three-column classification for
      all the categories are as follows: (I-III) k2D = 0.718, 95% CI 0.554-0.864, p <
      0.0001 and average 3D = 0.874, 95% CI 0.754-0.890, p < 0.0001. For Schatzker
      classification system, the average values for all six categories are as follows:
      (I-VI) k2D = 0.536, 95% CI 0.365-0.685, p < 0.0001 and average k3D = 0.552 95% CI
      0.405-0.700, p < 0.0001. The values are statistically significant. CONCLUSION:
      Statistically significant inter-observer values in both rounds were noted with
      the three-column classification, making it statistically an excellent agreement.
      The intra-observer reproducibility for the three-column classification improved
      as compared with the Schatzker classification. The three-column classification
      seems to be an effective way to characterise and classify fractures of tibial
      plateau.

PMID- 24013814
TI  - A modified posterolateral approach for Hoffa fracture.

PMID- 24013815
TI  - Acrometastases.
AB  - Metastases distal to the elbow and the knee (acrometastases) are rare, accounting
      for approximately 0.1 % of all cases. Acrometastases can appear in patients of
      every age, with men being twice as likely as women to be affected. The most
      common primary cancer site is the lung (>50 %), followed by the colon, breast and
      genito-urinary tract. They mainly appear in cancer patients with wide-spread
      disseminated disease. Rarely, they may be the first presentation of occult silent
      cancer, mimicking a benign condition. Current evidence supports that the tumor
      cells reach the bones of the hands through the circulation and not the lymphatic
      system; the malignant cells from the lungs have an easy access through the
      arterial circulation of the arms. The rare incidence of foot acrometastases is
      believed to be due to the lack of red marrow in these bones, a further distance
      from the primary cancer site, and the valveless paravertebral venous plexuses
      (Batson's plexuses), which allow retrograde tumor cell embolization through the
      iliofemoral venous system. Treatment depends on staging and tumor extent.
      Amputative surgery is the more common approach, especially for cancers with poor
      response to radiation therapy and chemotherapy. In the majority of cases,
      disarticulation of the ray is required to achieve wide margin resection. In the
      foot, amputation can be that of a ray, midfoot or transtibial, depending on the
      location and spread of the tumor. If unresectable, palliative treatment with
      radiation therapy, bisphosphonates and chemotherapy is recommended. The prognosis
      of the patients with acrometastatic cancer is poor; the mean survival time after
      diagnosis is <6 months. An exception seems to be the patients with renal cell
      carcinoma, if treated with radical surgical resection, and a long latency period
      between nephrectomy and metastasis has occurred. 

PMID- 24013817
TI  - Wrinkled-graphene enriched MoO3 nanobelts with increased conductivity and reduced
      stress for enhanced electrochemical performance.
AB  - MoO3 has long suffered from poor conductivity and cyclability, which limit its
      high rate performance and ultralong cycling ability. Increasing the electronic
      conductivity with electron pathways of cathode materials can effectively enhance
      the lithium storage properties with stable cyclability and rate capability
      theoretically. Here the MoO3-reduced graphene oxide (rGO) hybrid nanobelts were
      designed and prepared and were tested as cathode materials for lithium batteries.
      It is demonstrated that the rGO is wrinkled and twisted around MoO3 nanobelts
      after reacting under high temperature and pressure conditions. The unique
      morphology of rGO, which has continuous electron pathways and stress buffering
      effects, endows the MoO3-rGO hybrid nanobelts with significantly increased rate
      capability and cycling ability. Meanwhile, it is demonstrated that MoO3-rGO
      hybrid nanobelts are promising cathode materials for use in rechargeable lithium
      batteries and our synthesis strategy is also versatile for exploiting advanced
      materials for Li-ion batteries. 

PMID- 24013816
TI  - Cumulative association between age-related macular degeneration and less studied
      genetic variants in PLEKHA1/ARMS2/HTRA1: a meta and gene-cluster analysis.
AB  - The objective of this study is to examine the cumulative effect of the less
      studied genetic variants in PLEKHA1/ARMS2/HTRA1 on age-related macular
      degeneration (AMD). We performed an extensive literature search for studies on
      the association between AMD and the less studied genetic variants in
      PLEKHA1/ARMS2/HTRA1. Multiple meta-analyses were performed to evaluate the
      association between individual genetic variants and AMD. A gene-cluster analysis
      was used to investigate the cumulative effect of these less studied genetic
      variants on AMD. A total of 23 studies from 20 published papers met the
      eligibility criteria and were included in our analyses. Several genetic variants
      in the gene cluster are significantly associated with AMD in our meta-analyses or
      in individual studies. Gene-cluster analysis reveals a strong cumulative
      association between these genetic variants in this gene cluster and AMD (p < 10(
      5)). However, two previously suspected SNPs in ARMS2, including rs2736911, the
      SNP having the largest number of studies in our meta-analyses; and rs3793917, the
      SNP with the largest sample size, were not significantly associated with AMD
      (both p's > 0.12). Sensitivity analyses reveal significant association of AMD
      with rs2736911 in Chinese but not in Caucasian, with c.372_815del443ins54 in
      Caucasian but not in Chinese, and with rs1049331 in both ethnic groups. These
      less studied genetic variants have a significant cumulative effect on wet AMD.
      Our study provides evidence of the joint contribution of genetic variants in
      PLEKHA1/ARMS2/HTRA1 to AMD risk, in addition to the two widely studied genetic
      variants whose association with AMD was well established.

PMID- 24013818
TI  - Dynamic CT myocardial perfusion imaging: performance of 3D semi-automated
      evaluation software.
AB  - OBJECTIVES: To evaluate the performance of three-dimensional semi-automated
      evaluation software for the assessment of myocardial blood flow (MBF) and blood
      volume (MBV) at dynamic myocardial perfusion computed tomography (CT). METHODS:
      Volume-based software relying on marginal space learning and probabilistic
      boosting tree-based contour fitting was applied to CT myocardial perfusion
      imaging data of 37 subjects. In addition, all image data were analysed manually
      and both approaches were compared with SPECT findings. Study endpoints included
      time of analysis and conventional measures of diagnostic accuracy. RESULTS: Of
      592 analysable segments, 42 showed perfusion defects on SPECT. Average analysis
      times for the manual and software-based approaches were 49.1 +/- 11.2 and 16.5 +/
      3.7 min respectively (P < 0.01). There was strong agreement between the two
      measures of interest (MBF, ICC = 0.91, and MBV, ICC = 0.88, both P < 0.01) and no
      significant difference in MBF/MBV with respect to diagnostic accuracy between the
      two approaches for both MBF and MBV for manual versus software-based approach;
      respectively; all comparisons P > 0.05. CONCLUSIONS: Three-dimensional semi
      automated evaluation of dynamic myocardial perfusion CT data provides similar
      measures and diagnostic accuracy to manual evaluation, albeit with substantially
      reduced analysis times. This capability may aid the integration of this test into
      clinical workflows. KEY POINTS: * Myocardial perfusion CT is attractive for
      comprehensive coronary heart disease assessment. * Traditional image analysis
      methods are cumbersome and time-consuming. * Automated 3D perfusion software
      shortens analysis times. * Automated 3D perfusion software increases
      standardisation of myocardial perfusion CT. * Automated, standardised analysis
      fosters myocardial perfusion CT integration into clinical practice.

PMID- 24013819
TI  - Solid-state NMR spectroscopy structure determination of a lipid-embedded
      heptahelical membrane protein.
AB  - Determination of structure of integral membrane proteins, especially in their
      native environment, is a formidable challenge in structural biology. Here we
      demonstrate that magic angle spinning solid-state NMR spectroscopy can be used to
      determine structures of membrane proteins reconstituted in synthetic lipids, an
      environment similar to the natural membrane. We combined a large number of
      experimentally determined interatomic distances and local torsional restraints to
      solve the structure of an oligomeric membrane protein of common seven-helical
      fold, Anabaena sensory rhodopsin (ASR). We determined the atomic resolution
      detail of the oligomerization interface of the ASR trimer, and the arrangement of
      helices, side chains and the retinal cofactor in the monomer. 

PMID- 24013821
TI  - Posttransplant lymphoproliferative disorder in pediatric patients.
AB  - Transplantation of solid organs and hematopoietic stem cells is accompanied by
      profound disturbance of immune function mediated by immunosuppressive drugs or
      delayed immune reconstitution. Disturbed T cell control of Epstein-Barr virus
      (EBV)-infected B cells leads to posttransplant lymphoproliferative disorder
      (PTLD) in up to 10% of patients. Children are at a higher risk because they are
      more often EBV-naive before transplantation. Patients with PTLD often present
      with unspecific symptoms (pain and organ/graft dysfunction). Depending on the
      onset of PTLD, manifestations vary between mainly nodal (late PTLD) and
      extranodal sites (early PTLD). Histology, immunohistology, EBER in situ
      hybridization and molecular pathology are required for diagnosis and
      subclassification of PTLD. The three major types are early lesions (resembling
      reactive proliferations in immunocompetent patients), polymorphic PTLD
      (proliferation of B and T cells with effacement of histoarchitecture) and
      monomorphic PTLD (presenting as malignant lymphomas, mainly high-grade B cell
      lymphomas). In a subfraction of cases, including monomorphic PTLD, reduction of
      immunosuppressive medication alone is sufficient to induce remission. Surgical
      debulking of tumor mass and anti-CD20-antibody treatment with or without
      chemotherapy (usually at lower dosages than in immunocompetent patients)
      constitute the basis of additional therapy. 

PMID- 24013820
TI  - Brain-wide 3D imaging of neuronal activity in Caenorhabditis elegans with
      sculpted light.
AB  - Recent efforts in neuroscience research have been aimed at obtaining detailed
      anatomical neuronal wiring maps as well as information on how neurons in these
      networks engage in dynamic activities. Although the entire connectivity map of
      the nervous system of Caenorhabditis elegans has been known for more than 25
      years, this knowledge has not been sufficient to predict all functional
      connections underlying behavior. To approach this goal, we developed a two-photon
      technique for brain-wide calcium imaging in C. elegans, using wide-field temporal
      focusing (WF-TeFo). Pivotal to our results was the use of a nuclear-localized,
      genetically encoded calcium indicator, NLS-GCaMP5K, that permits unambiguous
      discrimination of individual neurons within the densely packed head ganglia of C.
      elegans. We demonstrate near-simultaneous recording of activity of up to 70% of
      all head neurons. In combination with a lab-on-a-chip device for stimulus
      delivery, this method provides an enabling platform for establishing functional
      maps of neuronal networks. 

PMID- 24013822
TI  - Directional plasticity rapidly improves 3D vestibulo-ocular reflex alignment in
      monkeys using a multichannel vestibular prosthesis.
AB  - Bilateral loss of vestibular sensation can be disabling. We have shown that a
      multichannel vestibular prosthesis (MVP) can partly restore vestibular sensation
      as evidenced by improvements in the 3-dimensional angular vestibulo-ocular reflex
      (3D VOR). However, a key challenge is to minimize misalignment between the axes
      of eye and head rotation, which is apparently caused by current spread beyond
      each electrode's targeted nerve branch. We recently reported that rodents wearing
      a MVP markedly improve 3D VOR alignment during the first week after MVP
      activation, probably through the same central nervous system adaptive mechanisms
      that mediate cross-axis adaptation over time in normal individuals wearing prisms
      that cause visual scene movement about an axis different than the axis of head
      rotation. We hypothesized that rhesus monkeys would exhibit similar improvements
      with continuous prosthetic stimulation over time. We created bilateral vestibular
      deficiency in four rhesus monkeys via intratympanic injection of gentamicin. A
      MVP was mounted to the cranium, and eye movements in response to whole-body
      passive rotation in darkness were measured repeatedly over 1 week of continuous
      head motion-modulated prosthetic electrical stimulation. 3D VOR responses to
      whole-body rotations about each semicircular canal axis were measured on days 1,
      3, and 7 of chronic stimulation. Horizontal VOR gain during 1 Hz, 50  degrees /s
      peak whole-body rotations before the prosthesis was turned on was <0.1, which is
      profoundly below normal (0.94 +/- 0.12). On stimulation day 1, VOR gain was 0.4
      0.8, but the axis of observed eye movements aligned poorly with head rotation
      (misalignment range ~30-40  degrees ). Substantial improvement of axis
      misalignment was observed after 7 days of continuous motion-modulated prosthetic
      stimulation under normal diurnal lighting. Similar improvements were noted for
      all animals, all three axes of rotation tested, for all sinusoidal frequencies
      tested (0.05-5 Hz), and for high-acceleration transient rotations. VOR asymmetry
      changes did not reach statistical significance, although they did trend toward
      slight improvement over time. Prior studies had already shown that directional
      plasticity reduces misalignment when a subject with normal labyrinths views
      abnormal visual scene movement. Our results show that the converse is also true:
      individuals receiving misoriented vestibular sensation under normal viewing
      conditions rapidly adapt to restore a well-aligned 3D VOR. Considering the
      similarity of VOR physiology across primate species, similar effects are likely
      to occur in humans using a MVP to treat bilateral vestibular deficiency.

PMID- 24013823
TI  - Citrate inhibition of cisplatin reaction with DNA studied using fluorescently
      labeled oligonucleotides: implication for selectivity towards guanine.
AB  - The reaction between cisplatin and DNA is conveniently studied using
      fluorescently labeled oligonucleotides and gel electrophoresis; as an example of
      application, the inhibition of this reaction by citrate is demonstrated, which
      might increase selectivity of cisplatin towards guanine over adenine. 

PMID- 24013825
TI  - Noninvasive control of the power transferred to an implanted device by an
      ultrasonic transcutaneous energy transfer link.
AB  - Ultrasonic transcutaneous energy transfer is an effective method for powering
      implanted devices noninvasively. Nevertheless, the amount of power harvested by
      the implanted receiver is sensitive to the distance and orientation of the
      external transmitting transducer attached to the skin with respect to the
      implanted receiving transducer. This paper describes an ultrasonic power transfer
      link whose harvested power is controlled by an inductive link. A small (5 MUF)
      storage capacitor voltage, which is part of the implanted unit, is allowed to
      swing between 3.8 and 3.5 V using hysteretic control. The two control states are
      indicated by excitation (while the implanted storage capacitor voltage decreases)
      or the absence of excitation of an implanted coil that is magnetically coupled to
      an external coil attached to the skin surface. A 35 mW Ultrasonic Transcutaneous
      Energy Transfer link was fabricated using two piezoelectric transducers of equal
      size (Fuji Ceramics C-2 PZT disc 15 mm * 3 mm) operated at a vibration frequency
      of 720 kHz. By applying the proposed hysteretic control, the captured power was
      effectively regulated for implantation depths of up to 85 mm. 

PMID- 24013824
TI  - Region specific response of intervertebral disc cells to complex dynamic loading:
      an organ culture study using a dynamic torsion-compression bioreactor.
AB  - The spine is routinely subjected to repetitive complex loading consisting of
      axial compression, torsion, flexion and extension. Mechanical loading is one of
      the important causes of spinal diseases, including disc herniation and disc
      degeneration. It is known that static and dynamic compression can lead to
      progressive disc degeneration, but little is known about the mechanobiology of
      the disc subjected to combined dynamic compression and torsion. Therefore, the
      purpose of this study was to compare the mechanobiology of the intervertebral
      disc when subjected to combined dynamic compression and axial torsion or pure
      dynamic compression or axial torsion using organ culture. We applied four
      different loading modalities [1. control: no loading (NL), 2. cyclic compression
      (CC), 3. cyclic torsion (CT), and 4. combined cyclic compression and torsion
      (CCT)] on bovine caudal disc explants using our custom made dynamic loading
      bioreactor for disc organ culture. Loads were applied for 8 h/day and continued
      for 14 days, all at a physiological magnitude and frequency. Our results provided
      strong evidence that complex loading induced a stronger degree of disc
      degeneration compared to one degree of freedom loading. In the CCT group, less
      than 10% nucleus pulposus (NP) cells survived the 14 days of loading, while cell
      viabilities were maintained above 70% in the NP of all the other three groups and
      in the annulus fibrosus (AF) of all the groups. Gene expression analysis revealed
      a strong up-regulation in matrix genes and matrix remodeling genes in the AF of
      the CCT group. Cell apoptotic activity and glycosaminoglycan content were also
      quantified but there were no statistically significant differences found. Cell
      morphology in the NP of the CCT was changed, as shown by histological evaluation.
      Our results stress the importance of complex loading on the initiation and
      progression of disc degeneration. 

PMID- 24013826
TI  - Sleep and wakefulness state detection in nocturnal actigraphy based on movement
      information.
AB  - Wrist actigraphy (ACT) is a low-cost and well-established technique for long-term
      monitoring of human activity. It has a special relevance in sleep studies, where
      its noninvasive nature makes it a valuable tool for behavioral characterization
      and for the detection and diagnosis of some sleep disorders. The traditional
      sleep/wakefulness state estimation algorithms from the nocturnal ACT data are
      unbalanced from a sensitivity and specificity points of view since they tend to
      overestimate sleep state, with severe consequences from a diagnosis point of
      view. They usually maximize the overall accuracy that does not take into account
      the highly unbalanced state distribution. In this paper, a method is proposed to
      appropriately deal with this unbalanced problem, achieving similar sensitivity
      and specificity scores in the state estimation process. The proposed method
      combines two linear discriminant classifiers, trained with two different criteria
      involving movement detection to generate a first state estimate. This result is
      then refined by a Hidden Markov Model-based algorithm. The global accuracy, the
      sensitivity, and the specificity of the method are 77.8%, 75.6%, and 81.6%,
      respectively, performing better than the tested algorithms. If the performance is
      assessed only for movement periods, this improvement is even higher.

PMID- 24013827
TI  - Optimization of measurement arrangements for magnetic detection electrical
      impedance tomography.
AB  - Magnetic detection electrical impedance tomography (MDEIT) is an imaging modality
      that aims to compute the cross-sectional distribution of the conductivity inside
      a volume. The current is injected into the volume by the surface electrodes and
      the resulting magnetic fields surrounding the object are detected by coils. The
      image resolution and contrast in MDEIT image reconstruction are affected by the
      parameters such as the numbers and locations of electrodes and measurements, and
      the finite-element mesh resolution. This paper addresses the numerical experiment
      applied to the singular value analysis (SVA) of the sensitivity matrix in the
      presence of noisy measurements, subsequently suggesting the optimal electrode and
      detector configurations for the whole imaging object region. For the region of
      interest (RoI), the combined SVA and redundancy reduction is used to obtain the
      optimum measurement arrangement. Finally, the optimum design is confirmed by
      examining the image reconstructions of the simulated data acquired with different
      measurement arrangements. The results indicate that properly increasing the
      number of current injections and the number of measurement circles, and locating
      preferentially the electrodes and detectors on the region nearest to the RoI
      produce more useful singular values and better reconstructed images. These
      results provide guidelines for the design of the MDEIT experimental system.

PMID- 24013828
TI  - Predicting and evaluating the effect of bivalirudin in cardiac surgical patients.
AB  - Bivalirudin, used in patients with heparin-induced thrombocytopenia, is a direct
      thrombin inhibitor. Since it is a rarely used drug, clinical experience with its
      dosing is sparse. We develop two approaches to predict the Partial Thromboplastin
      Time (PTT) based on bivalirudin infusion rates. The first approach is model free
      and utilizes regularized regression. It is flexible enough to be used as
      predictors bivalirudin infusion rates measured over several time instances before
      the time at which a PTT prediction is sought. The second approach is model based
      and proposes a specific model for obtaining PTT which uses a shorter history of
      the past measurements. We learn population-wide model parameters by solving a
      nonlinear optimization problem. We also devise an adaptive algorithm based on the
      extended Kalman filter that can adapt model parameters to individual patients.
      The latter adaptive model emerges as the most promising as it yields reduced mean
      error compared to the model-free approach. The model accuracy we demonstrate on
      actual patient measurements is sufficient to be useful in guiding the optimal
      therapy.

PMID- 24013830
TI  - Adaptive neural network output feedback control for stochastic nonlinear systems
      with unknown dead-zone and unmodeled dynamics.
AB  - This paper discusses the problem of adaptive neural network output feedback
      control for a class of stochastic nonlinear strict-feedback systems. The
      concerned systems have certain characteristics, such as unknown nonlinear
      uncertainties, unknown dead-zones, unmodeled dynamics and without the direct
      measurements of state variables. In this paper, the neural networks (NNs) are
      employed to approximate the unknown nonlinear uncertainties, and then by
      representing the dead-zone as a time-varying system with a bounded disturbance.
      An NN state observer is designed to estimate the unmeasured states. Based on both
      backstepping design technique and a stochastic small-gain theorem, a robust
      adaptive NN output feedback control scheme is developed. It is proved that all
      the variables involved in the closed-loop system are input-state-practically
      stable in probability, and also have robustness to the unmodeled dynamics.
      Meanwhile, the observer errors and the output of the system can be regulated to a
      small neighborhood of the origin by selecting appropriate design parameters.
      Simulation examples are also provided to illustrate the effectiveness of the
      proposed approach. 

PMID- 24013829
TI  - The microbial spectrum of neonatal sepsis in Uganda: recovery of culturable
      bacteria in mother-infant pairs.
AB  - Neonatal sepsis in the developing world is incompletely characterized. We seek to
      characterize the microbial spectrum involved in sepsis and determine the role of
      maternal transmission by comparing organisms that can be cultured from septic
      newborn infants and their mothers. From 80 consecutive mother-infant pairs
      meeting clinical criteria for neonatal sepsis, we collected infant blood and
      spinal fluid, and maternal blood and vaginal specimens. Identifiable bacteria
      were recovered from the blood in 32.5% of infants, and from 2.5% of cerebrospinal
      fluid cultures, for a total of 35% recoverable putative causative agents.
      Bacteria recovered from vaginal specimens were not concordant with those
      recovered from infants. Similarly there was no concordance of bacteria recovered
      from blood and cerebrospinal fluid. We conclude that relying on traditional
      bacterial culture techniques does not adequately delineate the role of maternal
      versus environmental sources of neonatal sepsis in this setting. More sensitive
      molecular approaches will be needed to properly characterize the maternal and
      environmental microbial community involved in neonatal sepsis in such developing
      countries. 

PMID- 24013831
TI  - A reduced-complexity data-fusion algorithm using belief propagation for location
      tracking in heterogeneous observations.
AB  - This paper presents a low-complexity and high-accuracy algorithm to reduce the
      computational load of the traditional data-fusion algorithm with heterogeneous
      observations for location tracking. For the location-estimation technique with
      the data fusion of radio-based ranging measurement and speed-based sensing
      measurement, the proposed tracking scheme, based on the Bayesian filtering
      concept, is handled by a state space model. The location tracking problem is
      divided into many mutual-interaction local constraints with the inherent message-
      passing features of factor graphs. During each iteration cycle, the messages with
      reliable information are passed efficiently between the prediction phase and the
      correction phase to simplify the data-fusion implementation for tracking the
      location of the mobile terminal. Numerical simulations show that the proposed
      forward and one-step backward refining tracking approach that combines radio
      ranging with speed sensing measurements for data fusion not only can achieve an
      accurate location close to that of the traditional Kalman filtering data-fusion
      algorithm, but also has much lower computational complexity. 

PMID- 24013832
TI  - Mathematical biodynamic feedthrough model applied to rotorcraft.
AB  - Biodynamic feedthrough (BDFT) occurs when vehicle accelerations feed through the
      human body and cause involuntary control inputs. This paper proposes a model to
      quantitatively predict this effect in rotorcraft. This mathematical BDFT model
      aims to fill the gap between the currently existing black box BDFT models and
      physical BDFT models. The model structure was systematically constructed using
      asymptote modeling, a procedure described in detail in this paper. The resulting
      model can easily be implemented in many typical rotorcraft BDFT studies, using
      the provided model parameters. The model's performance was validated in both the
      frequency and time domain. Furthermore, it was compared with several recent BDFT
      models. The results show that the proposed mathematical model performs better
      than typical black box models and is easier to parameterize and implement than a
      recent physical model. 

PMID- 24013833
TI  - Nonparallel support vector machines for pattern classification.
AB  - We propose a novel nonparallel classifier, called nonparallel support vector
      machine (NPSVM), for binary classification. Our NPSVM that is fully different
      from the existing nonparallel classifiers, such as the generalized eigenvalue
      proximal support vector machine (GEPSVM) and the twin support vector machine
      (TWSVM), has several incomparable advantages: 1) two primal problems are
      constructed implementing the structural risk minimization principle; 2) the dual
      problems of these two primal problems have the same advantages as that of the
      standard SVMs, so that the kernel trick can be applied directly, while existing
      TWSVMs have to construct another two primal problems for nonlinear cases based on
      the approximate kernel-generated surfaces, furthermore, their nonlinear problems
      cannot degenerate to the linear case even the linear kernel is used; 3) the dual
      problems have the same elegant formulation with that of standard SVMs and can
      certainly be solved efficiently by sequential minimization optimization
      algorithm, while existing GEPSVM or TWSVMs are not suitable for large scale
      problems; 4) it has the inherent sparseness as standard SVMs; 5) existing TWSVMs
      are only the special cases of the NPSVM when the parameters of which are
      appropriately chosen. Experimental results on lots of datasets show the
      effectiveness of our method in both sparseness and classification accuracy, and
      therefore, confirm the above conclusion further. In some sense, our NPSVM is a
      new starting point of nonparallel classifiers. 

PMID- 24013834
TI  - Differential evolution with two-level parameter adaptation.
AB  - The performance of differential evolution (DE) largely depends on its mutation
      strategy and control parameters. In this paper, we propose an adaptive DE (ADE)
      algorithm with a new mutation strategy DE/lbest/1 and a two-level adaptive
      parameter control scheme. The DE/lbest/1 strategy is a variant of the greedy
      DE/best/1 strategy. However, the population is mutated under the guide of
      multiple locally best individuals in DE/lbest/1 instead of one globally best
      individual in DE/best/1. This strategy is beneficial to the balance between fast
      convergence and population diversity. The two-level adaptive parameter control
      scheme is implemented mainly in two steps. In the first step, the population
      level parameters Fp and CRp for the whole population are adaptively controlled
      according to the optimization states, namely, the exploration state and the
      exploitation state in each generation. These optimization states are estimated by
      measuring the population distribution. Then, the individual-level parameters Fi
      and CRi for each individual are generated by adjusting the population-level
      parameters. The adjustment is based on considering the individual's fitness value
      and its distance from the globally best individual. This way, the parameters can
      be adapted to not only the overall state of the population but also the
      characteristics of different individuals. The performance of the proposed ADE is
      evaluated on a suite of benchmark functions. Experimental results show that ADE
      generally outperforms four state-of-the-art DE variants on different kinds of
      optimization problems. The effects of ADE components, parameter properties of
      ADE, search behavior of ADE, and parameter sensitivity of ADE are also studied.
      Finally, we investigate the capability of ADE for solving three real-world
      optimization problems. 

PMID- 24013835
TI  - Robust mixed l(1)/H(infinity) filtering for affine fuzzy systems with measurement
      errors.
AB  - This paper investigates the robust filtering problem for a class of nonlinear
      systems described by affine fuzzy parts with norm-bounded uncertainties. The
      system outputs are chosen as the premise variables of fuzzy models, and their
      measured values are chosen as the premise variables and inputs of fuzzy filters.
      The measurement errors between the outputs of the plant and the inputs of the
      filter are considered, and as a result, the plant and the estimator cannot always
      evolve in the same region at the same time, especially in the neighborhoods of
      region boundaries. By using a piecewise Lyapunov function combined with S
      procedure and adding slack matrix variables, a fuzzy-basis-dependent mixed
      l1/Hinfinity filter design method is obtained in the formulation of linear matrix
      inequalities, which allows for reducing the worst case peak output due to the
      measurement errors, and satisfying an Hinfinity -norm constraint. In contrast to
      existing work, the proposed fuzzy-basis-dependent filter can guarantee a better
      Hinfinity performance and less computational burden. Finally, a numerical example
      illustrates the effectiveness of the proposed method. 

PMID- 24013836
TI  - Combined hepatocellular-cholangiocarcinoma producing parathyroid hormone-related
      protein: report of a case.
AB  - Combined hepatocellular-cholangiocarcinoma (CHCC) is an uncommon form of primary
      liver cancer. A 57-year-old man was readmitted to our hospital for treatment of
      recurrent CHCC, 12 months after central bisegmentectomy and 4 months after
      limited hepatic resection. Magnetic resonance imaging (MRI) revealed multiple
      hepatic nodules. Laboratory data showed increased serum levels of alpha
      fetoprotein (AFP), calcium, and parathyroid hormone-related protein (PTH-rP), to
      5,571 ng/mL, 17.0 mg/dL, and 16.1 pmol/L, respectively. Palliative mass reduction
      surgery was indicated by the fact that the hypercalcemia was difficult to manage
      medically. Thus, we performed lateral segmentectomy with partial resection of
      segment 7 and the caudate lobe, and microwave coagulation therapy for multiple
      recurrent CHCC. Thereafter, the serum PTH-rP and AFP levels decreased remarkably
      and the hypercalcemia was controlled for the next 3 months. He died of disease
      progression 9 months after the last hepatic surgery. To our knowledge, this is
      only the second reported case of CHCC producing PTH-rP in the English-language
      literature. 

PMID- 24013837
TI  - Impact of second-line and later cetuximab-containing therapy and KRAS genotypes
      in patients with metastatic colorectal cancer: a multicenter study in Japan.
AB  - PURPOSES: This retrospective study evaluated the treatment outcomes and clinical
      relevance of the KRAS mutation status in Japanese metastatic colorectal cancer
      patients treated with second-line and later cetuximab-containing therapy.
      METHODS: The subjects comprised 65 patients with metastatic colorectal cancer who
      received cetuximab-containing therapy. At the start of cetuximab-containing
      therapy, the KRAS mutation status had been proven to be wild type in 12 patients.
      Tumors were retrospectively screened for KRAS mutations using direct sequencing.
      RESULTS: A detailed analysis revealed the presence of 24 wild-type (57.1 %) and
      18 mutant tumors (42.9 %). Grade 3-4 neutropenia and anemia were observed in 21
      (32.3 %) and nine (13.8 %) patients, respectively. An acne-like rash was observed
      in 50 patients (76.9 %), and among them three patients (4.6 %) experienced a
      Grade 3 rash. A KRAS mutation was associated with resistance to cetuximab
      containing treatment (11.1 vs. 41.7 % responders among 18 mutant and 36 wild-type
      patients, respectively; P = 0.03). A KRAS mutation was also associated with
      poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients,
      respectively; P = 0.018). CONCLUSIONS: The present results indicated the clinical
      relevance of KRAS mutations in predicting the efficacy of cetuximab-containing
      therapy for metastatic colorectal patients in the Japanese population.

PMID- 24013838
TI  - Among patients with sustained viral suppression in a resource-limited setting,
      CD4 gains are continuous although gender-based differences occur.
AB  - INTRODUCTION: There is conflicting data on long-term CD4 immune recovery after
      combination antiretroviral therapy (ART) in resource-limited settings. Virologic
      suppression is rarely documented in cohorts from sub-Saharan Africa so objective
      evidence of adherence is biologically unsubstantiated. We sought to investigate
      long-term patterns of immune recovery in Ugandan patients on ART with sustained
      viral suppression. METHODS: A prospective cohort of patients starting ART between
      April, 2004 and April, 2005 at the Infectious Diseases Institute with sustained
      viral suppression (viral load <= 400 copies/ml at month 6 and 12) while on first
      line ART. Propensity scores were used to adjust for treatment allocation
      (nevirapine or efavirenz) at ART initiation. Data were analyzed using Kaplan
      Meier methods and cross-sectional time series regression. RESULTS: Three hundred
      and fifty-six patients were included in the analysis.71.6% were female, 87% in
      WHO stage 3 or 4, median age was 37 years, (IQR:32-43), and median CD4 count was
      108 cells/uL, (IQR:35-174) at ART start. At multivariable analysis, lower immune
      recovery (measured by change in CD4 from ART start at each time interval) was
      associated with male-gender (-59, 95% CI: 90, -28, P<0.001), baseline CD4 count
      of 101-200 cells/uL (-35, 95% CI: 62, -9, P=0.009) and >200 (-64, 95% CI: 101, 
      26, P=0.001), and use of AZT at baseline (-47, 95% CI: -74, -20, P=0.001). Median
      time to reach >400 cells/uL was longer in males (197.4 weeks, IQR:119.9-312.0),
      compared to females (144.7 weeks, IQR:96.6-219.7, P<0.001). The cumulative
      probability of attaining CD4 >400 cells/uL over 7 years was higher in females
      compared to males (P<0.001). CONCLUSIONS: There was long-term, continuous,
      immunologic recovery up to 7 years after ART initiation in an urban Ugandan
      cohort. Virologically suppressed women had better sustained immune recovery than
      men. Men take longer to immune reconstitute and have a lower probability of
      reaching a CD4 cell count >400 cells/uL. The biologic mechanisms of these gender
      differences need further exploration.

PMID- 24013839
TI  - Better reporting of scientific studies: why it matters.

PMID- 24013841
TI  - How to educate and evaluate cardiothoracic surgeon.

PMID- 24013840
TI  - Sustained impact of inattention and hyperactivity-impulsivity on peer problems:
      mediating roles of prosocial skills and conduct problems in a community sample of
      children.
AB  - This prospective 2-year longitudinal study tested whether inattentive and
      hyperactive/impulsive symptom dimensions predicted future peer problems, when
      accounting for concurrent conduct problems and prosocial skills. A community
      sample of 492 children (49 % female) who ranged in age from 6 to 10 years (M =
      8.6, SD = .93) was recruited. Teacher reports of children's inattention, and
      hyperactivity/impulsivity symptoms, conduct problems, prosocial skills and peer
      problems were collected in two consecutive school years. Elevated inattention and
      hyperactivity/impulsivity in Year-1 predicted greater peer problems in Year-2.
      Conduct problems in the first and second years of the study were associated with
      more peer problems, and explained a portion of the relationship between
      inattention and hyperactivity/impulsivity with peer problems. However, prosocial
      skills were associated with fewer peer problems in children with elevated
      inattention and hyperactivity/impulsivity. Inattention and
      hyperactivity/impulsivity have negative effects on children's peer functioning
      after 1-year, but concurrent conduct problems and prosocial skills have important
      and opposing impacts on these associations. 

PMID- 24013842
TI  - The Role of Implicit Measurement in the Assessment of Risky Behavior: A Pilot
      Study with African American Girls.
AB  - With the aim of developing a novel strategy for identifying vulnerability for
      early sexual activity and adjustment problems, African American girls (n = 39)
      completed partially structured scenarios in which female characters of similar
      age faced circumstances characterized by varying levels of risk. Most girls
      indicated that they believed the characters would have sex, regardless of their
      own sexual history or the level of risk in the scenario. However, the combination
      of girls' sexual history and girls' predictions of characters' behavior in the
      scenario provided more information regarding the girls at greatest risk for
      adjustment problems. Implicit techniques offer an additional strategy for
      identifying girls most vulnerable to adjustment difficulties in the context of
      early sexual activity.

PMID- 24013843
TI  - Macrophage polarization in response to wear particles in vitro.
AB  - Total joint replacement is a highly successful surgical procedure for treatment
      of patients with disabling arthritis and joint dysfunction. However, over time,
      with high levels of activity and usage of the joint, implant wear particles are
      generated from the articulating surfaces. These wear particles can lead to
      activation of an inflammatory reaction, and subsequent bone resorption around the
      implant (periprosthetic osteolysis). Cells of the monocyte/macrophage lineage
      orchestrate this chronic inflammatory response, which is dominated by a pro
      inflammatory (M1) macrophage phenotype rather than an anti-inflammatory pro
      tissue healing (M2) macrophage phenotype. While it has been shown that
      interleukin-4 (IL-4) selectively polarizes macrophages towards an M2 anti
      inflammatory phenotype which promotes bone healing, rather than inflammation,
      little is known about the time course in which this occurs or conditions in which
      repolarization through IL-4 is most effective. The goal of this work was to study
      the time course of murine macrophage polarization and cytokine release in
      response to challenge with combinations of polymethyl methacrylate (PMMA)
      particles, lipopolysaccharide (LPS) and IL-4 in vitro. Treatment of particle
      challenged monocyte/macrophages with IL-4 led to an initial suppression of pro
      inflammatory cytokines and inducible nitric oxide synthase (iNOS) production and
      subsequent polarization into an M2 anti-inflammatory phenotype. This result was
      optimized when IL-4 was delivered before PMMA particle challenge, to an M1
      phenotype rather than to uncommitted (M0) macrophages. The effects of this
      polarization were sustained over a 5-day time course. Polarization of M1
      macrophages into an M2 phenotype may be a strategy to mitigate wear particle
      associated periprosthetic osteolysis. 

PMID- 24013846
TI  - Recent advances in the chemoselective reduction of functional groups mediated by
      samarium(II) iodide: a single electron transfer approach.
AB  - Recently, samarium(II) iodide reductants have emerged as powerful single electron
      donors for the highly chemoselective reduction of common functional groups.
      Complete control of the product formation can be achieved on the basis of a
      judicious choice of a Sm(II) complex/proton donor couple, even in the presence of
      extremely sensitive functionalities (iodides, aldehydes). In most cases, the
      reductions are governed by thermodynamic control of the first electron transfer,
      which opens up new prospects for unprecedented transformations via radical
      intermediates under mild regio-, chemo- and diastereoselective conditions that
      are fully orthogonal to hydrogenation or metal-hydride mediated processes.

PMID- 24013844
TI  - The DNA-binding factor Ctcf critically controls gene expression in macrophages.
AB  - Macrophages play an important role in immunity and homeostasis. Upon pathogen
      recognition via specific receptors, they rapidly induce inflammatory responses.
      This process is tightly controlled at the transcriptional level. The DNA binding
      zinc-finger protein CCCTC-binding factor (Ctcf) is a crucial regulator of long
      range chromatin interactions and coordinates specific communication between
      transcription factors and gene expression processes. In this study, the Ctcf gene
      was specifically deleted in myeloid cells by making use of the transgenic Cre
      LoxP system. Conditional deletion of the Ctcf gene in myeloid cells induced a
      mild phenotype in vivo. Ctcf-deficient mice exhibited significantly reduced
      expression of major histocompatibility complex (MHC) class II in the liver. Ctcf
      deficient macrophages demonstrated a normal surface phenotype and phagocytosis
      capacity. Upon Toll-like receptor (TLR) stimulation, they produced normal levels
      of the pro-inflammatory cytokines IL-12 and IL-6, but manifested a strongly
      impaired capacity to produce tumor-necrosis factor (TNF) and IL-10, as well as to
      express the IL-10 family members IL-19, IL-20 and IL-24. Taken together, our data
      demonstrate a role of Ctcf that involves fine-tuning of macrophage function. 

PMID- 24013845
TI  - Treatment of allergic inflammation and hyperresponsiveness by a simple compound,
      Bavachinin, isolated from Chinese herbs.
AB  - Asthmatic inflammation is mediated by a type 2 helper T cell (Th2) cytokine
      response, and blocking Th2 cytokine production is proven to have a potent
      therapeutic effect against asthmatic inflammation. Using IL-4-green fluorescent
      protein (GFP) reporter mice, we demonstrated that Bavachinin, a single compound
      isolated from a Chinese herb, significantly inhibited Th2 cytokine production,
      including IL-4, IL-5 and IL-13. Notably, this compound almost completely blocked
      inflammation in the ovalbumin (OVA)-sensitized animal asthma model. Furthermore,
      we demonstrated that this chemical selectively affects the level of GATA-3, most
      likely by affecting the stability of GATA-3 mRNA. Our results demonstrate, for
      the first time, the potential therapeutic value of this single compound derived
      from Chinese herbs. 

PMID- 24013847
TI  - MRI features associated with acute appendicitis.
AB  - OBJECTIVES: To identify MRI features associated with appendicitis. METHODS:
      Features expected to be associated with appendicitis were recorded in consensus
      by two expert radiologists on 223 abdominal MRIs in patients with suspected
      appendicitis. Nine MRI features were studied: appendix diameter >7 mm,
      appendicolith, peri-appendiceal fat infiltration, peri-appendiceal fluid, absence
      of gas in the appendix, appendiceal wall destruction, restricted diffusion of the
      appendiceal wall, lumen or focal fluid collections. Appendicitis was assigned as
      the final diagnosis in 117/223 patients. Associations between imaging features
      and appendicitis were evaluated with logistic regression analysis. RESULTS: All
      investigated features were significantly associated with appendicitis in
      univariate analysis. Combinations of two and three features were associated with
      a probability of appendicitis of 88 % and 92 %, respectively. In patients without
      any of the nine features, appendicitis was present in 2 % of cases. After
      multivariate analysis, only an appendix diameter >7 mm, peri-appendiceal fat
      infiltration and restricted diffusion of the appendiceal wall were significantly
      associated with appendicitis. The probability of appendicitis was 96 % in their
      presence and 2 % in their absence. CONCLUSIONS: An appendix diameter >7 mm, peri
      appendiceal fat infiltration and restricted diffusion of the appendiceal wall
      have the strongest association with appendicitis on MRI. KEY POINTS: * An
      enlarged appendix, fat infiltration and restricted diffusion are associated with
      appendicitis. * One such feature on MRI gives an 88 % probability of
      appendicitis. * Two features in combination give a probability of appendicitis of
      94 %. * Combinations of three features give a probability of appendicitis of 96
      %. * The absence of these features almost rules out appendicitis (2 %).

PMID- 24013848
TI  - Head and neck tumours: combined MRI assessment based on IVIM and TIC analyses for
      the differentiation of tumors of different histological types.
AB  - OBJECTIVES: We evaluated the combined use of intravoxel incoherent motion (IVIM)
      and time-signal intensity curve (TIC) analyses to diagnose head and neck tumours.
      METHODS: We compared perfusion-related parameters (PP) and molecular diffusion
      values (D) determined from IVIM theory and TIC profiles among 92 tumours with
      different histologies. RESULTS: IVIM parameters (f and D values) and TIC profiles
      in combination were distinct among the different types of head and neck tumours,
      including squamous cell carcinomas (SCCs), lymphomas, malignant salivary gland
      tumours, Warthin's tumours, pleomorphic adenomas and schwannomas. A
      multiparametric approach using both IVIM parameters and TIC profiles
      differentiated between benign and malignant tumours with 97 % accuracy and
      diagnosed different tumour types with 89 % accuracy. CONCLUSIONS: Combined use of
      IVIM parameters and TIC profiles has high efficacy in diagnosing head and neck
      tumours. KEY POINTS: * Head and neck tumours have wide MR perfusion/diffusion
      properties. * Dynamic contrast-enhanced (DCE) MR imaging can characterise tumour
      perfusion (TIC analysis). * Intravoxel incoherent motion (IVIM) imaging can
      provide diffusion and perfusion properties. * However, IVIM or DCE imaging alone
      is insufficient for diagnosing head/neck tumours. * Multiparametric approach
      using both IVIM and TIC profiles can facilitate the diagnosis.

PMID- 24013849
TI  - Successful Recruitment of Centenarians for Post-Mortem Brain Donation: Results
      from the Georgia Centenarian Study.
AB  - OBJECTIVE: Brain donation and neuropathological examination of brain tissues is
      the only way to obtain definitive diagnostic information on research subjects
      enrolled in aging studies. We investigated predictors of brain donation in a
      population-based study of centenarians in Phase III of the Georgia Centenarian
      Study (GCS). METHODS: Sixty-six individuals (mean age = 100.6 years, 91% female,
      20% African American) were successfully recruited from the core sample of 244
      individuals residing in 44 counties of Northeast Georgia to provide brain
      donation. RESULTS: Bivariate (t-tests, chi-square tests) and multivariate
      analyses (logistic regression) showed no significant differences between donors
      and non-donors across a wide range of demographic, religious, personality,
      cognitive and physical functioning characteristics. CONCLUSIONS: We succeeded in
      recruiting a diverse, population-based sample of centenarians for brain donation.
      Our findings also suggest that barriers to brain donation reported in other
      studies may have less impact in these exceptional survivors.

PMID- 24013851
TI  - Risk factors for non-adherence to antidepressant treatment in patients with mood
      disorders.
AB  - PURPOSE: Adherence to antidepressant therapy by patients with depressive
      disorders is essential not only to achieve a positive patient outcome but also to
      prevent a relapse. The aim of this study was to identify potential modelling
      factors influencing adherence to antidepressant treatment by patients with mood
      disorders in the community mental health care setting METHODS: A total of 160
      consecutive psychiatric outpatients attending two Community Mental Health Centres
      on Tenerife Island between September 2011 and May 2012 were asked to participate
      in the study; of these, 145 accepted. The Morisky self-report scale was used to
      assess adherence. The potential predictors examined included socio-demographic,
      clinical and therapeutic variables. The Clinical Global Impression-Severity and 
      Improvement scales and the Beck Depression Inventory were used for clinical
      assessment. Drug treatment side-effects were assessed using the "Self-report
      Antidepressant Side-Effect Checklist." All participants were also asked to
      complete the "Drug Attitude Inventory" (DAI), "Beliefs about Medicine
      Questionnaire" (BMQ), and "Leeds Attitude towards concordance Scale".
      Discriminant analyses were performed to predict non-adherence. RESULTS: There was
      no clear correlation between adherence and the socio-demographic variables
      examined, but adherence was related to a positive attitude of the patients
      towards his/her treatment (DAI) and low scores in the BMQ-Harm and -Concern
      subscales. Non-adherence was also related to an increasing severity of depression
      and to the presence and severity of side-effects. CONCLUSIONS: Among our study
      cohort, the profiles of adherent patients to antidepressant treatment were more
      closely associated with each patient's attitudes and beliefs than to objective
      socio-demographic variables. The severity of depression played a relevant role in
      adherence, but whether this role is direct or an interaction with several
      concurrent factors is not yet clear. Side-effects were also closely related to
      adherence, as conditioned by frequent polypharmacy.

PMID- 24013852
TI  - Prefrontal control of cerebellum-dependent associative motor learning.
AB  - Behavioral studies have demonstrated that both medial prefrontal cortex (mPFC)
      and cerebellum play critical roles in trace eyeblink conditioning. However,
      little is known regarding the mechanism by which the two brain regions interact.
      By use of electrical stimulation of the caudal mPFC as a conditioned stimulus, we
      show evidence that persistent outputs from the mPFC to cerebellum are necessary
      and sufficient for the acquisition and expression of a trace conditioned response
      (CR)-like response. Specifically, the persistent outputs of caudal mPFC are
      relayed to the cerebellum via the rostral part of lateral pontine nuclei.
      Moreover, interfering with persistent activity by blockade of the muscarinic Ach
      receptor in the caudal mPFC impairs the expression of learned trace CRs. These
      results suggest an important way for the caudal mPFC to interact with the
      cerebellum during associative motor learning. 

PMID- 24013853
TI  - Ataxia, intellectual disability, and ocular apraxia with cerebellar cysts: a new
      disease?
AB  - Cerebellar cysts are rare findings in pediatric neuroimaging and rather
      characteristic for dystroglycanopathies and GPR56-related encephalopathy. We aim
      to report on seven children with cerebellar cysts showing absence of weakness and
      ruling out mutations within eight dystroglycanopathy genes and GPR56. Data about
      neurological and ophthalmological features, outcome, and creatine kinase values
      were collected from clinical histories and follow-up examinations. All MR images
      were qualitatively evaluated for infra- and supratentorial abnormalities. A SNP
      6.0-Array was performed in three children. The POMT1, POMT2, POMGnT1, FKRP, FKTN,
      LARGE, ISPD, B3GALNT2, and GPR56 genes were screened in all patients by Sanger
      sequencing. Seven children from five families were studied. Ataxia, intellectual
      disability, and language impairment were found in all patients, ocular motor
      apraxia in five, and severe myopia in three. None of the patients had weakness,
      only three a minimally increased creatine kinase value. Qualitative neuroimaging
      evaluation showed cerebellar cysts and dysplasia in the cerebellar hemispheres
      and vermis in all children. Additional findings were an enlarged fourth ventricle
      in all children, vermian hypoplasia and brain stem morphological abnormalities in
      five. The SNP array showed no pathogenetic imbalances in all children evaluated.
      In all patients, no mutations were found in POMT1, POMT2, POMGnT1, FKRP, FKTN,
      LARGE, ISPD, B3GALNT2, and GPR56. The peculiar combination of the same clinical
      and neuroimaging findings in our patients highly suggests that this phenotype may
      represent a novel entity, possibly falling within the spectrum of
      dystroglycanopathies. 

PMID- 24013854
TI  - Gender differences in disability-free life expectancy at old ages in Bangladesh.
AB  - OBJECTIVE: We examined gender differences in the prevalence of disability and
      Disability-free Life Expectancy (DFLE) for Bangladeshi older adults. METHOD: We
      used data representing 4,189 elderly subjects aged 60 years and over from a
      nationally representative survey (Bangladesh's Household Income and Expenditure
      Survey-2010). The Sullivan method was used to compute DFLE. RESULTS: Eyesight
      disability is prevalent among 28.94 and 36.47 men and women, respectively, and is
      the most prevalent type of disability in Bangladesh. Women have each disability
      and at least one disability in significantly higher percentages than men. At all
      ages, and in both numbers and proportion, women have longer life expectancy but
      shorter DFLE than men. DISCUSSION: Attention should be given to the elderly, with
      special care devoted to elderly women. The findings of the current study have
      important implications for risk of disability and the need for, and use of, long
      term care services.

PMID- 24013855
TI  - Health problems and marital satisfaction among older couples.
AB  - OBJECTIVE: Older couples are likely to be confronted with health problems of both
      spouses and these health problems may negatively influence their marital
      satisfaction. The present study examined these possible negative effects using a
      dyadic perspective. METHOD: Data from 78 independently living older couples were
      analyzed using the Actor-Partner Interdependence Model (APIM). Health problems
      were modeled as a latent factor of functional disability, the number of chronic
      diseases, and self-rated health. The couple's health context, that is, similarity
      or dissimilarity, was examined with an actor-partner interaction variable.
      RESULTS: For wives, spousal health problems were negatively associated with their
      marital satisfaction, but only under the condition that their own health was
      relatively good. For husbands, neither own nor spousal health problems were
      associated with their marital satisfaction. DISCUSSION: Future research focusing
      on older couples needs to consider the couple's health context next to health at
      the individual level.

PMID- 24013856
TI  - Dihydrogen activation by a tungsten-alkylidyne complex: toward photoredox
      chromophores that deliver renewable reducing equivalents.
AB  - The d(1) tungsten-alkylidyne radical [W(CPh)(dppe)2Cl](+) reacts with H2 to give
      the d(0) hydride [W(CPh)(H)(dppe)2Cl](+), which on deprotonation yields the d(2)
      photoredox chromophore W(CPh)(dppe)2Cl. This family of reactions results in a
      cycle by which renewable H2 provides the reducing equivalents for photochemical
      reductions. 

PMID- 24013858
TI  - Antimicrobial activity of electrospun poly(butylenes succinate) fiber mats
      containing PVP-capped silver nanoparticles.
AB  - In this study, biodegradable poly(butylenes succinate) (PBS) fiber mats
      containing silver nanoparticles (AgNPs) were prepared by the electrospinning
      process. Small AgNPs (<10 nm) were simply synthesized using polyvinylpyrrolidone
      as the capping agent as well as the reductant. The morphology of the PBS-AgNPs
      fiber mats and the distribution of the AgNPs were well characterized by TEM and
      SEM. The release of Ag from the PBS fiber mats was quantitively determined by
      ICP. The PBS fiber mats with 0.29 % AgNPs content showed strong antimicrobial
      activity against both gram-positive Staphylococcus aureus and gram-negative
      Escherichia coli with the efficacy as high as 99 %. The effective bactericidal
      activity on E. coli was demonstrated for a short contacting time with the PBS
      AgNPs fiber mats. In addition, the long-term release performance of Ag from the
      fiber mats can keep inhibiting the bacterial growth in the mats over a long
      period of time.

PMID- 24013857
TI  - Longitudinal myocardial peak velocities using high temporal resolution phase
      contrast and simple averaging are comparable to tissue Doppler echocardiography.
AB  - OBJECT: Phase contrast imaging is widely used to measure blood velocity. However
      tissue Doppler imaging (TDI) echocardiography is the reference for myocardial
      velocity assessment. This study aims at validating the ability of phase contrast
      (PC) sequences to correctly assess myocardial velocities and to compare these
      velocities to TDI. The phase contrast sequence was performed with breath-hold
      parameters and with parameters tuned to increase temporal resolution in free
      breathing. MATERIALS AND METHODS: Left and Right auriculo-ventricular annuluses
      longitudinal velocities were recorded on six healthy volunteers with different
      temporal resolutions (TDI: 5 ms, breath-hold PC: 94 ms and free-breathing PC: 19
      ms). Free-breathing PC was obtained by averaging of three excitations. Amplitudes
      of four standard echocardiographic and clinically relevant myocardial
      longitudinal velocity waves were compared: Early filling and auricular, systolic
      and isovolumic contractions. RESULTS: Isovolumic contraction waves were only
      visible with free-breathing PC and TDI. The differences with the reference TDI
      wave velocities were lower (p = 0.02) for free-breathing PC (19.2 +/- 2.6%) than
      for breath-hold PC (28.1 +/- 2.9%). These differences for free-breathing PC were
      close to (p = 0.21) the coefficient of variation of the measurements provided by
      TDI (14.8 +/- 1.2%). CONCLUSION: Myocardial longitudinal peak velocities can be
      assessed with a PC sequence tuned to optimize temporal resolution.

PMID- 24013859
TI  - Growth, osmolyte concentration and antioxidant enzymes in the leaves of Sesuvium
      portulacastrum L. under salinity stress.
AB  - In this study, growth and osmolyte concentration in the leaves of halophyte,
      Sesuvium portulacastrum, were studied with respect to salinity. Therefore, the
      changes in shoot growth, leaf tissue water content, osmolyte concentration
      (proline content, glycine betaine) and antioxidant enzymes [polyphenol oxidase
      (PPO), superoxide dismutase (SOD) and catalase (CAT)] were investigated. The 30
      day old S. portulacastrum plants were subjected to 100, 200, 300, 400, 500 and
      600 mM NaCl for 28 days. The plant growth was steadily increased up to 500 mM
      NaCl stress at 28 days. TWC was higher in 300 mM NaCl treated leaves than that of
      600 mM NaCl. Salinity stress induced the accumulation of osmolyte concentration
      when compared to control during the study period. The antioxidant enzymes PPO,
      CAT and SOD were increased under salinity.

PMID- 24013860
TI  - Growth of Chlorella vulgaris on sugarcane vinasse: the effect of anaerobic
      digestion pretreatment.
AB  - Microalgae farming has been identified as the most eco-sustainable solution for
      producing biodiesel. However, the operation of full-scale plants is still limited
      by costs and the utilization of industrial and/or domestic wastes can
      significantly improve economic profits. Several waste effluents are valuable
      sources of nutrients for the cultivation of microalgae. Ethanol production from
      sugarcane, for instance, generates significant amounts of organically rich
      effluent, the vinasse. After anaerobic digestion treatment, nutrient remaining in
      such an effluent can be used to grow microalgae. This research aimed to testing
      the potential of the anaerobic treated vinasse as an alternative source of
      nutrients for culturing microalgae with the goal of supplying the biodiesel
      industrial chain with algal biomass and oil. The anaerobic process treating
      vinasse reached a steady state at about 17 batch cycles of 24 h producing about
      0.116 m(3)CH4 kgCODvinasse (-1). The highest productivity of Chlorella vulgaris
      biomass (70 mg l(-1) day(-1)) was observed when using medium prepared with the
      anaerobic digester effluent. Lipid productivity varied from 0.5 to 17 mg l(-1)
      day(-1). Thus, the results show that it is possible to integrate the culturing of
      microalgae with the sugarcane industry by means of anaerobic digestion of the
      vinasse. There is also the advantageous possibility of using by-products of the
      anaerobic digestion such as methane and CO2 for sustaining the system with energy
      and carbon source, respectively.

PMID- 24013861
TI  - An ancestral member of the polysaccharide lyase family 2 displays endolytic
      activity and magnesium dependence.
AB  - Polysaccharide lyases (PLs) are enzymes that cleave glycosidic linkages in
      hexuronate polysaccharides, such as homogalacturonan (HG), using a beta
      elimination mechanism. Traditionally, PL activities on HG have been associated
      with catalytic calcium cofactors, unusually high pH optima, and arginine
      Bronstead bases. Recently, however, PL families that harness transition metal
      cofactors, utilize lysine and histidine Bronstead bases, and display more neutral
      pH optima have been described. One such family is PL2, which has members found
      primarily in phytopathogenic (e.g., Dickeya spp. and Pectobacterium spp.) or
      enteropathogenic (e.g., Yersinia spp.) bacterial species. PL2 is divided into two
      major subfamilies that are correlated with either an endolytic or exolytic
      activity. This study has focused on the activity of a PL2 member, which is not
      classified within either subfamily and helps to illuminate the origin of enzyme
      activities within the family. In addition, the role of Mg(2+) as a preferential
      catalytic metal for an intracellular PL2 (PaePL2) is described. The implications
      for the relationship between catalytic metal selectivity and the cellular
      location of pectate lyase-mediated catalysis are discussed. 

PMID- 24013862
TI  - Microsporum fulvum IBRL SD3: as novel isolate for chicken feathers degradation.
AB  - Keratinous wastes have increasingly become a problem and accumulate in the
      environment mainly in the form of feathers, generated mainly from a large number
      of poultry industries. As keratins are very difficult to degrade by general
      proteases, they pose a major environmental problem. Therefore, microorganisms
      which would effectively degrade keratins are needed for recycling such wastes. A
      geophilic dermatophyte, Microsporum fulvum IBRL SD3 which was isolated from a
      soil sample collected from a chicken feather dumping site using a baiting
      technique, was capable to produce keratinase significantly. The crude keratinase
      was able to degrade whole chicken feathers effectively. The end product of the
      degradation was protein that contained essential amino acids and may have
      potential application in animal feed production. Thus, M. fulvum could be a novel
      organism to produce keratinase for chicken feathers degradation. 

PMID- 24013864
TI  - No dedicated second-order motion system.
AB  - The existence of a second-order motion system distinct from both the first-order
      and feature tracking motion systems remains controversial even though many
      consider it well established. In the present study, the texture contribution to
      motion was measured within and beyond the spatial acuity of attention by
      presenting the stimuli in the near periphery where the spatial resolution of
      attention is low. The logic was that when moving elements are too close one to
      another for attention to individually select them (i.e., crowding), it is not
      possible to track them. To test the existence of a dedicated second-order motion
      system, the texture contribution to motion was measured when neutralizing both
      the feature tracking motion system and the contribution of the first-order motion
      system due to preprocessing nonlinearities introducing residual distortion
      products. When the contribution of distortion products was not neutralized,
      texture substantially contributed to motion for spatial frequencies within and
      beyond the spatial acuity of attention. When neutralizing the contribution of
      distortion products, texture substantially contributed to motion for spatial
      frequencies within the spatial acuity of attention, but not for spatial
      frequencies beyond the spatial acuity of attention. We conclude that there is no
      dedicated second-order motion system; the texture contribution to motion is
      mediated solely by the first-order (due to residual distortion products) and
      feature tracking (at frequencies within spatiotemporal acuity of attention)
      motion systems. 

PMID- 24013863
TI  - Co-expression of receptors of the HER family correlates with clinical outcome in
      non-small cell lung cancer (NSCLC).
AB  - HER family receptors play a critical role in lung carcinogenesis. There is a
      growing body of evidence showing that cooperation between them contributes to a
      more aggressive tumor phenotype and impacts on their response to targeted
      therapy. We explored immunohistochemical co-expression of HER family receptors
      (HER1, HER2, HER3, HER4) and its potential role as prognostic factor in resected
      non-small cell lung cancer (NSCLC). Expression of HER family receptors was
      assessed by immunohistochemistry on 125 surgically resected NSCLC. Kaplan-Meier
      estimates of overall survival (OS), disease-free survival (DFS), and time to
      recurrence were calculated for clinical variables and HER expression, using the
      Cox model for multivariate analysis. HER1 and HER3 expression was detected more
      frequently in squamous cell carcinoma (p = 0.002 and p = <0.001, respectively).
      HER4 was more often expressed in patients older than 60 years (p = 0.02) and in
      tumors of low histological grade (p = 0.04). Cases which expressed only HER1 had
      a worse DFS (p = 0.01) and OS (p = 0.01) compared to cases expressing HER1 and
      one or more of the other family members and to cases which did not express HER1
      but one of the other HERs. By multivariate analysis, stage was an independent
      prognostic factor for DFS and OS. Furthermore, different patterns of co
      expression of HER family receptors showed a statistically significant correlation
      with a shorter DFS (p = 0.03) and OS (p = 0.02). Our findings suggest that
      expression of HER1 only is correlated with worse DFS and OS. A better
      understanding of the functional relationships between these receptors may lead to
      a useful predictive indicator of response to targeted therapy.

PMID- 24013865
TI  - Depth and luminance edges attract.
AB  - The spatial resolution of disparity perception is poor compared to luminance
      perception, yet we do not notice that depth edges are more blurry than luminance
      edges. Is this because the two cues are combined by the visual system? Subjects
      judged the locations of depth-defined or luminance-defined edges, which were
      separated by up to 5.6 min of arc. The perceived edge location was a function of
      the depth-defined edge and the luminance-defined edge, with the luminance edge
      tending to play a larger role. Our data are compatible with but not completely
      explained by an optimal cue-combination model that gives more reliable cues a
      heavier weight. Both edge cues (depth and luminance) contribute to the final
      percept, with an adaptive weighting depending on the task and the acuity with
      which each cue is perceived. 

PMID- 24013866
TI  - Vision in water.
AB  - The purpose of this study is to determine visual performance in water, including
      the influence of pupil size. The water environment was simulated by placing
      goggles filled with saline in front of the eyes with apertures placed at the
      front of the goggles. Correction factors were determined for the different
      magnification under this condition in order to estimate vision in water.
      Experiments were conducted on letter visual acuity (seven participants), grating
      resolution (eight participants), and grating contrast sensitivity (one
      participant). For letter acuity, mean loss of vision in water, compared to
      corrected vision in air, varied between 1.1 log min of arc resolution (logMAR)
      for a 1 mm aperture to 2.2 logMAR for a 7 mm aperture. The vision in min of arc
      was described well by a linear relationship with pupil size. For grating acuity,
      mean loss varied between 1.1 logMAR for a 2 mm aperture to 1.2 logMAR for a 6 mm
      aperture. Contrast sensitivity for a 2 mm aperture deteriorated as spatial
      frequency increased with a 2 log unit loss by 3 c/ degrees . Superimposed on this
      deterioration were depressions (notches) in sensitivity with the first three
      notches occurring at 0.45, 0.8, and 1.3 c/ degrees  with estimates for water of
      0.39, 0.70, and 1.13 c/ degrees . In conclusion, vision in water is poor. It
      becomes worse as pupil size increases, but the effects are much more marked for
      letter targets than for grating targets. 

PMID- 24013867
TI  - Validation of a new neurological score (FOUR Score) in the assessment of
      neurosurgical patients with severely impaired consciousness.
AB  - BACKGROUND: The Glasgow coma scale (GCS) was introduced as a scoring system for
      patients with impaired consciousness after traumatic brain injury (TBI). Since,
      it has become the worldwide standard in TBI assessment. The GCS has repeatedly
      been criticized for its several failures to reflect verbal reaction in intubated
      patients, and to test brain stem reflexes. Recently, the full outline of
      unresponsiveness (FOUR) score was introduced, which is composed of four
      clinically distinct categories of evaluation: eye reaction, motor function,
      brainstem reflexes and respiratory pattern. This study aims to validate the FOUR
      score in neurosurgical patients. METHODS: FOUR score and GCS were assessed in a
      consecutive series of neurosurgical patients with severely impaired consciousness
      (GCS < 9). Their correlation with the 30-day Glasgow outcome score (GOS) was
      compared. Patients admitted for TBI, spontaneous intracranial hemorrhage
      (intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, cerebellar
      hemorrhage), or malignant middle cerebral artery infarction were included.
      RESULTS: We assessed a total of 101 patients (mean age = 64y, SD = 36.1y). The
      area under the curve (AUC) for mortality was 0.768 (P = 0.0001) for the FOUR
      Score, and 0.699 (P = 0.001) for the GCS. For poor outcome (GOS = 2-3) the FOUR
      score AUC was 0.683 (P = 0.018), the GCS AUC was 0.682 (P = 0.019). The FOUR
      score value for favorable outcome (GOS = 4-5) was 0.748 (P = 0.001), the
      corresponding GCS value was 0.704 (P = 0.002). CONCLUSIONS: The FOUR score was
      more robust than the GCS in predicting mortality after 30 days in neurosurgical
      patients with severely impaired consciousness. There was no relevant difference
      in predicting poor and good outcome.

PMID- 24013869
TI  - An assessment of intrathecal catheters in the perioperative period: an analysis
      of 84 cases.
AB  - BACKGROUND: Intrathecal opioid administration yields high quality analgesia with
      an associated low incidence of side effects and complication. The benefits of
      spinal "opioid only technique" include absence of neuronal blockade, infusion
      pump malfunction and sympathetic blockade. This technique declined after serious
      side effects were reported in the 1990s. AIMS: To report on the safety and
      efficacy of the intrathecal catheter repeat bolus morphine technique for
      postoperative analgesia in patients having thoracotomy. METHODS: A 22 gauge
      intrathecal catheter was inserted through the lumbar 3-4 interspace prior to
      induction of anaesthesia for postoperative analgesia. Repeat bolus preservative
      free morphine was administered for 48 h, target VAS was <4. RESULTS: The mean
      morphine administered via ITC in 48 h was 2.56 mg (+/- SD 0.88 mg). Only one
      patient required rescue morphine. There were no serious complications or sequelae
      at 6-month follow-up. CONCLUSIONS: Intrathecal morphine for post-op analgesia is
      efficacious and safe in a post-thoracotomy population.

PMID- 24013868
TI  - A dose-response study of arsenic exposure and global methylation of peripheral
      blood mononuclear cell DNA in Bangladeshi adults.
AB  - BACKGROUND: Several studies employing cell culture and animal models have
      suggested that arsenic (As) exposure induces global DNA hypomethylation. However,
      As has been associated with global DNA hypermethylation in human study
      populations. We hypothesized that this discrepancy may reflect a nonlinear
      relationship between As dose and DNA methylation. OBJECTIVE: The objective of
      this study was to examine the dose-response relationship between As and global
      methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy
      Bangladeshi adults chronically exposed to a wide range of As concentrations in
      drinking water. METHODS: Global PBMC DNA methylation, plasma folate, blood S
      adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and
      urine were measured in 320 adults. DNA methylation was measured using the [3H]
      methyl incorporation assay, which provides disintegration-per-minute (DPM) values
      that are negatively associated with global DNA methylation. RESULTS: Water,
      blood, and urinary As were positively correlated with global PBMC DNA methylation
      (p < 0.05). In multivariable-adjusted models, 1-MUg/L increases in water and
      urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95%
      CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical
      models indicated that estimated mean levels of PBMC DNA methylation were highest
      in participants with the highest As exposures. CONCLUSIONS: These results suggest
      that As is positively associated with global methylation of PBMC DNA over a wide
      range of drinking water As concentrations. Further research is necessary to
      elucidate underlying mechanisms and physiologic implications.

PMID- 24013870
TI  - Prescribing of antidiabetic therapies in Ireland: 10-year trends 2003-2012.
AB  - BACKGROUND: Over the last decade there have been significant changes in the
      prescribing of antidiabetic therapies. It is of interest to know about these
      trends and variations in the Irish population so that future prescribing patterns
      can be estimated. AIMS: To examine the trends in prescribed antidiabetic
      treatments, including variations across age, gender, socioeconomic status and
      regions in the Irish population over the last 10 years. METHODS: The Irish
      national pharmacy claims database was used to identify patients >= 16 years
      dispensed antidiabetic agents (oral or insulin) from January 2003 to December
      2012 through the two main community drug schemes for diabetes. The rate of
      prescribing per 1,000 population was calculated. Logistic regression was used to
      examine variations in prescribing in patients with diabetes. RESULTS: There was a
      significant increase in the prescribing of fast and long-acting insulin analogues
      with a rapid decline in the prescribing of human insulin (p < 0.0001). Increased
      prescribing of metformin, incretin modulators and fixed oral combination agents
      was observed (p < 0.0001). Females and older aged patients were more likely to be
      prescribed human insulin than other insulins. Metformin was less likely while
      sulphonylureas were more likely to be prescribed in older than younger aged
      patients. Socioeconomic differences were observed in increased prescribing of the
      newer and more expensive antidiabetic agents in the non-means tested scheme.
      Regional variations were observed in the prescribing of both insulin and oral
      antidiabetic agents. CONCLUSION: There has been an increase over time in the
      prescribing of both insulin and oral antidiabetic agents in the Irish population
      with increasing uptake of newer antidiabetic agents. This has implications for
      projecting future uptake and expenditure of these agents given the rising level
      of diabetes in the population.

PMID- 24013871
TI  - Explaining the increase in breastfeeding at hospital discharge in Ireland, 2004
      2010.
AB  - BACKGROUND: Despite a steady increase in the rate of breastfeeding in Ireland
      over the period 2004-2010 (from 46.8 % in 2004 to 55.7 % in 2010), Irish rates of
      breastfeeding are still low by international standards. Over this period, the
      characteristics of mothers and babies changed, with mothers increasingly older,
      having fewer children and increasingly born outside the Republic of Ireland.
      AIMS: The purpose of this paper is to understand the extent to which changing
      maternal and birth characteristics explained the increase in the breastfeeding
      rate in Ireland over the period 2004-2010. METHODS: We apply non-linear
      decomposition techniques to micro-data from the 2004-2010 Irish National
      Perinatal Reporting System to examine this issue. The technique allows us to
      quantify the extent to which the increase in the breastfeeding rate over the
      period 2004-2010 is due to changing maternal and birth characteristics. RESULTS:
      We find that between 55 and 74 % of the increase over the period can be explained
      by changing characteristics, with the increasing share of mothers from Eastern
      Europe, and increasing maternal age the most important contributors. CONCLUSIONS:
      These findings suggest that the existing policy initiatives have been relatively
      ineffective in increasing breastfeeding rates in Ireland, i.e. most of the
      observed increase occurred simply because the characteristics of mothers were
      changing in ways that made them increasingly likely to breastfeed.

PMID- 24013872
TI  - Bioinspired, direct synthesis of aqueous CdSe quantum dots for high-sensitive
      copper(II) ion detection.
AB  - Luminescent CdSe semiconductor quantum dots (QDs), which are coated with a
      denatured bovine serum albumin (dBSA) shell, have been directly synthesized via a
      bioinspired approach. The dBSA coated CdSe QDs are ultrasmall (d < 2.0 nm) with a
      narrow size distribution and exhibit a strong green fluorescent emission at about
      525 nm. They can be stored for months at room temperature and possess excellent
      stability against ultraviolet irradiation, high salt concentration, and a wide
      physiological range of pH. Systematic experimental investigations have shown the
      contribution of dBSA with free cysteine residues for both their effective ion
      chelating and surface passivating interactions during the formation and
      stabilization of CdSe QDs. The luminescent QDs are used for copper(II) ion
      detection due to their highly sensitive and selective fluorescence quenching
      response to Cu(2+). The concentration dependence of the quenching effect can be
      best described by the typical Stern-Volmer equation in a linearly proportional
      concentration of Cu(2+) ranging from 10 nM to 7.5 MUM with a detection limit of 5
      nM. As confirmed by various characterization results, a possible quenching
      mechanism is given: Cu(2+) ions are first reduced to Cu(+) by the dBSA shell and
      then chemical displacement between Cu(+) and Cd(2+) is performed at the surface
      of the ultrasmall metallic core to impact the fluorescence performance.

PMID- 24013873
TI  - Transgenic Rat Models of Huntington's Disease.
AB  - Several animal models for Huntington's disease (HD) have been created in order to
      investigate mechanisms of disease, and to evaluate the potency of novel
      therapies. Here, we describe the characteristics of the two transgenic rat
      models: transgenic rat model of HD (fragment model) and the Bacterial Artificial
      Chromosome HD model (full-length model). We discuss their genetic, behavioural,
      neuropathological and neurophysiological features. 

PMID- 24013874
TI  - B7-H3-mediated tumor immunology: Friend or foe?
AB  - B7-H3 (CD276), a newly identified member of the B7 family of molecules, is often
      induced in human tumors and its overexpression is closely correlated with
      survival, prognosis or tumor grade. Although cancer immunotherapy has not been
      completely translated into clinical successes, interest has been further enhanced
      by the realization of these costimulatory molecules' potential as targets to
      modulate clinical immune responses. Despite ample evidence implicating B7-H3 in
      tumor immune escape, a steady flow of reports have suggested that it may also
      have antitumor effects under certain circumstances. The safety and efficacy of
      targeting B7-H3 with a monoclonal antibody for the treatment of advanced-stage
      central nervous system cancer in children has been proven, making B7-H3 an
      attractive therapeutic target for this kind of tumor. In addition, B7-H3 was
      shown to promote invasion and accelerate carcinogenesis in tumor progression
      according to its nonimmunological regulatory roles. In this review, we discuss
      current understanding of the diverse functions of B7-H3 in carcinogenesis and
      cancer progression, and consider future directions for designing cancer
      immunotherapeutic agents targeting B7-H3. 

PMID- 24013875
TI  - Comparing operational definitions of DSM-5 anorexia nervosa for research
      contexts.
AB  - OBJECTIVE: DSM-5 anorexia nervosa (AN) criteria include several changes that
      increase reliance on clinical judgment. However, research contexts require
      operational definitions that can be applied reliably and that demonstrate
      validity. The present study evaluated different operational definitions for DSM-5
      AN. METHOD: DSM-5 AN criteria were applied to diagnostic interview data from 364
      women varying two features: threshold for determining low weight for Criterion A
      (body mass index [BMI] <17.0 kg/m(2) vs. <18.5 kg/m(2)) and explicit endorsement
      of weight phobia (Criterion B explicit vs. inferred). Resulting groups of
      individuals with DSM-5 AN were compared on estimated frequency. In addition, AN
      groups were compared to non-eating disorder controls and individuals with an
      other specified feeding or eating disorder (OSFED) on external validators.
      RESULTS: All operational DSM-5 definitions produced higher lifetime frequency
      estimates than reported for DSM-IV AN, with a particularly large increase
      associated with the broadest definition. All definitions produced significant
      differences in comparison to controls on external validators that were associated
      with medium to large effect sizes. Only definitions that required a lower weight
      threshold or explicit endorsement of weight phobia demonstrated significant
      differences compared to OSFED on external validators, and these were of small
      effect size. The specific combination of BMI <18.5 kg/m(2) with inferred weight
      phobia exhibited few meaningful distinctions from the OSFED group. DISCUSSION: To
      balance inclusivity, syndromal reliability, and validity, an operational
      definition for DSM-5 AN in research contexts should define low weight as BMI
      <18.5 kg/m(2) and require measurable rather than inferred weight phobia.

PMID- 24013876
TI  - Guidewire advancement is interrupted by an internal jugular vein valve with a
      restricted opening: an ultrasound image.

PMID- 24013877
TI  - Facile fabrication of dextran-based fluorescent nanogels as potential glucose
      sensors.
AB  - Glucose-responsive nanogels based on dextran and poly(3-acrylamidophenylboronic
      acid) (PAAPBA) were fabricated by a facile self-assembly assisted (SAA) strategy.
      Further introduction of the fluorescent agent 2-[4-(3-hydroxy-4-oxo-4H-chromen-2
      yl)phenoxy]ethylacrylamide (3HF-AM) allowed visualization of this glucose
      sensitivity, thus ensuring their potential use as glucose sensors. 

PMID- 24013878
TI  - Experimental focal neocortical epilepsy is associated with reduced white matter
      volume growth: results from multiparametric MRI analysis.
AB  - Focal epilepsy has recently been associated with remote white matter damage,
      including reduced white matter volume. Longitudinal assessment of these white
      matter changes, in relation to functional mechanisms and consequences, may be
      ideally done by in vivo neuroimaging in well-controlled experimental animal
      models. We assessed whether advanced machine learning algorithm models could
      accurately detect volumetric changes in white matter from multiparametric MR
      images, longitudinally collected in a neocortical focal epilepsy rat model. We
      measured classification accuracy in two supervised segmentation models: i.e. the
      generalized linear model and the nonlinear random forest model-by comparing
      computed white matter probabilities with actual neuroanatomically identified
      white matter. We found excellent overall discriminatory power for both models.
      However, the random forest model demonstrated a superior goodness-of-fit
      calibration plot that was close to the ideal calibration line. Based on this
      model, we measured that total white matter volume increased in young adult
      control and epileptic rats over a period of 10 weeks, but the average white
      matter volume was significantly lower in the focal epilepsy group. Changes in
      gray matter volume were not significantly different between control and epileptic
      rats. Our results (1) indicate that recurrent spontaneous seizures have an
      adverse effect on global white matter growth and (2) show that individual whole
      brain white matter volume can be accurately determined using a combination of
      multiparametric MRI and supervised segmentation models, offering a powerful tool
      to assess white matter volume changes in preclinical studies of neurological
      disease.

PMID- 24013879
TI  - De Novo mutations in the beta-tubulin gene TUBB4: from DYT4 to
      leukoencephalopathy with hypomyelination with atrophy of the basal ganglia and
      cerebellum (H-ABC syndrome).

PMID- 24013880
TI  - Application of a chitosan-immobilized Talaromyces thermophilus lipase to a batch
      biodiesel production from waste frying oils.
AB  - Waste frying oil, which not only harms people's health but also causes
      environmental pollution, can be a good alternative to partially substitute
      petroleum diesel through transesterification reaction. This oil contained 8.8 %
      of free fatty acids, which cause a problem in a base-catalyzed process. In this
      study, synthesis of biodiesel was efficiently catalyzed by the covalently
      immobilized Talaromyces thermophilus lipase and allowed bioconversion yield up to
      92 % after 24 h of reaction time. The optimal molar ratio was four to six parts
      of methanol to one part of oil with a biocatalyst loaded of 25 wt.% of oil.
      Further, experiments revealed that T. thermophilus lipase, immobilized by a
      multipoint covalent liaison onto activated chitosan via a short spacer
      (glutaraldehyde), was sufficiently tolerant to methanol. In fact, using the
      stepwise addition of methanol, no significant difference was observed from the
      one-step whole addition at the start of reaction. The batch biodiesel synthesis
      was performed in a fixed bed reactor with a lipase loaded of 10 g. The
      bioconversion yield of 98 % was attained after a 5-h reaction time. The
      bioreactor was operated successfully for almost 150 h without any changes in the
      initial conversion yield. Most of the chemical and physical properties of the
      produced biodiesel meet the European and USA standard specifications of biodiesel
      fuels.

PMID- 24013881
TI  - Mode of antibacterial activity of Eclalbasaponin isolated from Eclipta alba.
AB  - The present study was undertaken to evaluate the mode of antibacterial activity
      of Eclalbasaponin isolated from Eclipta alba, against selected Gram-positive and
      Gram-negative bacteria. The probable chemical structure was determined by using
      various spectroscopic techniques such as Fourier transform infrared spectroscopy
      (FTIR) and mass spectroscopy. The antibacterial activity was evaluated by well
      diffusion technique, pH sensitivity, chemotaxis, and crystal violet assays.
      Eclalbasaponin showed clear zone of inhibition against both Bacillus subtilis and
      Pseudomonas aeruginosa and exhibited growth inhibition at the pH range of 5.5
      9.0. The isolated saponin exhibited its positive chemoattractant property for
      both bacterial strains. Results of crystal violet assay and the presence of UV
      sensitive materials in the cell-free supernatant confirmed the cellular damages
      caused by the treatment of Eclalbasaponin. The release of intracellular proteins
      due to the membrane damage was determined by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Changes in the cell surface structure and
      membrane disruption were further revealed by FTIR and scanning electron
      microscopy analysis. The present study suggests that the isolated saponin from E.
      alba causes the disruption of the bacterial cell membrane which leads to the loss
      of bacterial cell viability. 

PMID- 24013882
TI  - Improvement of regio-specific production of myricetin-3-O-alpha-L-rhamnoside in
      engineered Escherichia coli.
AB  - Myricetin is an important flavonol whose medically important properties include
      activities as an antioxidant, anticarcinogen, and antimutagen. The solubility,
      stability, and other biological properties of the compounds can be enhanced by
      conjugating aglycon with sugar moieties. The type of sugar moiety also plays a
      significant role in the biological and physical properties of the natural product
      glycosides. Reconstructed Escherichia coli containing thymidine diphosphate-alpha
      L-rhamnose sugar gene cassette and Arabidopsis-derived glycosyltransferase were
      used for rhamnosylation of myricetin. Myricetin (100 MUM) was exogenously
      supplemented to induced cultures of engineered E. coli. The formation of target
      product-myricetin-3-O-alpha-L-rhamnoside-was confirmed by chromatographic and NMR
      analyses. The yield of product was improved by using various mutants and
      methylated cyclodextrin as a molecular carrier for myricetin in combination with
      E. coli M3G3. The maximal yield of product is 55.6 MUM (3.31-fold higher than the
      control E. coli MG3) and shows 55.6 % bioconversion of substrate under optimized
      conditions.

PMID- 24013883
TI  - Anti-inflammatory and antinociceptive activity of chitin-binding lectin from
      Canna limbata seeds.
AB  - Lectins are a structurally heterogeneous group of proteins or glycoproteins with
      at least one noncatalytic domain binding reversibly to a specific mono- or
      oligosaccharide. Monocot mannose-binding lectins are an extended superfamily of
      structurally and evolutionarily related proteins. In this study, we evaluated
      anti-inflammatory and antinociceptive effects of monocot lectin from the Canna
      limbata seeds (CLL). To accomplish this, CLL was purified and subjected to
      pharmacological assays: abdominal writhing induced by acetic acid, formalin, hot
      plate and Zymosan A-induced peritonitis tests. The CLL was purified by
      chromatographic chitin column, and the relative mass of 21 kDa observed in
      electrophoresis was confirmed by electrospray mass spectrometry, which also
      revealed that purified CLL consists of a dimer having a weight of 49,676 Da. The
      CLL showed nociceptive activity in the acetic acid test as well as peripheral
      antinociceptive response. The CLL also showed anti-inflammatory effect with the
      reduction of inflammation in the formalin test and neutrophil migration into the
      peritoneal cavity. This is the first report of anti-inflammatory activity for a
      monocot lectin, and it suggests a new pharmacological tool to understand
      inflammatory and antinociceptive processes mediated through lectins.

PMID- 24013884
TI  - A newly isolated Pseudomonas sp., epibiotic on the seaweed, Padina
      tetrastromatica, off Southeastern Coast of India, reveals antibacterial action.
AB  - Epibionts from the red (Hypnea valentiae) and brown seaweeds (Padina
      tetrastromatica) were rapidly isolated on Zobell agar medium. All the isolates
      from both the seaweeds (76 numbers) were tested against five human pathogens
      which were resistant to at least one of the commercially available antibiotics at
      a minimal concentration of 10 mg. The most antibiotic productive isolate (PT19)
      from Padina tetrastromatica was extracted and observed to inhibit Klebsiella
      pneumoniae and Pseudomonas aeruginosa with zone sizes of 15 and 10 mm radius,
      respectively, at a concentration of 300 MUg. Further, a direct bioautography was
      done and an inhibition was witnessed against the aforementioned pathogens even at
      2 MUg concentration around three spots (R f values 0.6, 0.7, and 0.8).
      Preparative thin-layer chromatography yielded a yellow sticky compound (6 mg)
      which was identified as an alkaloid. The compound on reversed-phase high-pressure
      liquid chromatography analysis yielded two major and two minor peaks with
      retention times, 3.1, 4.2, 4.7, and 4.9 min, respectively. The antibacterial
      compound was recorded 96.6 % pure, and the producer strain was identified as
      Pseudomonas sp. To our knowledge, we are the first to isolate and identify
      Pseudomonas from Padina tetrastromatica producing antibacterial alkaloids. This
      study will pave way for exploring more bacterial load from the said algal groups
      for bioactivities.

PMID- 24013885
TI  - Nonsteroidal anti-inflammatory drugs diclofenac and celecoxib attenuates Wnt/beta
      catenin/Tcf signaling pathway in human glioblastoma cells.
AB  - Glioblastoma, the most common and aggressive primary brain tumors, carry a bleak
      prognosis and often recur even after standard treatment modalities. Emerging
      evidence suggests that deregulation of the Wnt/beta-catenin/Tcf signaling pathway
      contributes to glioblastoma progression. Nonsteroidal anti-inflammatory drugs
      (NSAIDs) inhibit tumor cell proliferation by suppressing Wnt/beta-catenin/Tcf
      signaling in various human malignancies. In this study, we sought to inhibit
      Wnt/beta-catenin/Tcf signaling in glioblastoma cells by the NSAIDs diclofenac and
      celecoxib. Both diclofenac and celecoxib significantly reduced the proliferation,
      colony formation and migration of human glioblastoma cells. Diclofenac and
      celecoxib downregulated beta-catenin/Tcf reporter activity. Western and qRT-PCR
      analysis showed that diclofenac and celecoxib reduced the expression of beta
      catenin target genes Axin2, cyclin D1 and c-Myc. In addition, the cytoplasmic
      accumulation and nuclear translocation of beta-catenin was significantly reduced
      following diclofenac and celecoxib treatment. Furthermore, diclofenac and
      celecoxib significantly increased phosphorylation of beta-catenin and reduced the
      phosphorylation of GSK3beta. These results clearly indicated that diclofenac and
      celecoxib are potential therapeutic agents against glioblastoma cells that act by
      suppressing the activation of Wnt/beta-catenin/Tcf signaling.

PMID- 24013886
TI  - Age-dependent effects of prenatal stress on the corticolimbic dopaminergic system
      development in the rat male offspring.
AB  - We have previously demonstrated that prenatal stress (PS) exerts an impairment of
      midbrain dopaminergic (DA) system metabolism especially after puberty, suggesting
      a particular sensitivity of DA development to variations in gonadal hormonal
      peaks. Furthermore we demonstrated that PS alters the long term androgens profile
      of the rat male offspring from prepubertal to adult stages. In this work we
      evaluated the sexual hormones activational effects on the DA system by analysing
      PS effects on the dopaminergic D2-like (D2R) and on the gonadal hormones receptor
      levels on cortical and hippocampal areas of prepubertal and adult male offspring.
      We further evaluated the dendritic arborization in the same areas by quantifying
      MAP2 immunoexpresion. Our results show that PS affected oestrogen receptor alpha
      (ERalpha) expression: mRNA er1s and ERalpha protein levels were decreased on
      prefrontal cortex and hippocampus of adult offspring. Moreover, PS reduced D2R
      protein levels in hippocampus of prepubertal rats. Morphological studies revealed
      that prepubertal PS rats presented decreased MAP2 immunoexpression in both areas
      suggesting that PS reduces the number of dendritic arborizations. Our findings
      suggest that PS exerts long-term effects on the DA system by altering the normal
      connectivity in the areas, and by modulating the expression of D2R and ERalpha in
      an age-related pattern. Since the developing forebrain DA system was shown to be
      influenced by androgen exposure, and PS was shown to disrupt perinatal
      testosterone surges, our results suggest that prenatal insults might be affecting
      the organizational role of androgens and differentially modulating their
      activational role on the DA development.

PMID- 24013887
TI  - Alterations on Na+,K+-ATPase and acetylcholinesterase activities induced by
      amyloid-beta peptide in rat brain and GM1 ganglioside neuroprotective action.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder whose pathogenesis
      involves production and aggregation of amyloid-beta peptide (Abeta). Abeta
      induced toxicity is believed to involve alterations on as Na(+),K(+)-ATPase and
      acetylcholinesterase (AChE) activities, prior to neuronal death. Drugs able to
      prevent or to reverse these biochemical changes promote neuroprotection. GM1 is a
      ganglioside proposed to have neuroprotective roles in AD models, through
      mechanisms not yet fully understood. Therefore, this study aimed to investigate
      the effect of Abeta1-42 infusion and GM1 treatment on recognition memory and on
      Na(+),K(+)-ATPase and AChE activities, as well as, on antioxidant defense in the
      brain cortex and the hippocampus. For these purposes, Wistar rats received i.c.v.
      infusion of fibrilar Abeta1-42 (2 nmol) and/or GM1 (0.30 mg/kg). Behavioral and
      biochemical analyses were conducted 1 month after the infusion procedures. Our
      results showed that GM1 treatment prevented Abeta-induced cognitive deficit,
      corroborating its neuroprotective function. Abeta impaired Na(+),K(+)-ATPase and
      increase AChE activities in hippocampus and cortex, respectively. GM1, in turn,
      has partially prevented Abeta-induced alteration on Na(+),K(+)-ATPase, though
      with no impact on AChE activity. Abeta caused a decrease in antioxidant defense,
      specifically in hippocampus, an effect that was prevented by GM1 treatment. GM1,
      both in cortex and hippocampus, was able to increase antioxidant scavenge
      capacity. Our results suggest that Abeta-triggered cognitive deficit involves
      region-specific alterations on Na(+),K(+)-ATPase and AChE activities, and that
      GM1 neuroprotection involves modulation of Na(+),K(+)-ATPase, maybe by its
      antioxidant properties. Although extrapolation from animal findings is difficult,
      it is conceivable that GM1 could play an important role in AD treatment.

PMID- 24013888
TI  - Selenium compounds prevent amyloid beta-peptide neurotoxicity in rat primary
      hippocampal neurons.
AB  - Neuropathological hallmarks of Alzheimer's disease (AD) include amyloid plaque
      formation, neurofibrillary tangles, neuronal and synaptic loss. This study aims
      to identify the neuroprotective effects of the selenium compounds on the
      neurotoxicity of amyloid beta(1-42) in primary cultures of murine hippocampal
      neurons. Samples were subjected to immunocytochemistry and western blotting
      techniques to determine the role of treatments on neuronal viability and synaptic
      protein SNAP-25. We observed a reduced cell viability amyloid beta-peptide (1-42)
      induced. When cells were co-treated with amyloid beta-peptide (1-42) and selenium
      compounds, we verified a strong increase in relative cell viability and in the
      level of synaptic marker synaptosomal-associated protein SNAP-25 induced by
      selenium compounds. 

PMID- 24013889
TI  - Screening of radical-scavenging natural neuroprotective antioxidants from Swertia
      chirayita.
AB  - To detect and identify natural antioxidants in Swertia chirayita with protective
      effect against cerebral infarction, a screening method, using column
      chromatography and cerebral ischemia-reperfusion injury in rat, was developed.
      Seventeen compounds were purposefully separated and identified by Nuclear
      Magnetic Resonance, Fourier Transform Infrared Spectroscopy, Ultraviolet
      Spectrum, and Mass Spectrometry. The purified compounds were further screened by
      radical scavenging activity and cerebral ischemia-reperfusion injury in rats. Two
      compounds showed apparent radical scavenging activity and neuroprotective
      activity. The two compounds were identified as 1-hydroxy-2,3,4,6
      tetramethoxyxanthone and 1,5,8-trihydroxy-3-methoxy xanthone, and were
      preliminarily considered as primary natural neuroprotective antioxidants in
      Swertia chirayita. These two compounds (20 mg kg-1) markedly decreased infarct
      size to below 5%, and also caused a significant improvement of activities of
      superoxide dismutase (SOD) (92.90 +/- 11.19 U ml-1), glutathione peroxidase (GSH
      Px) (122.58 +/- 12.31 MUmol mg-1) and a decrease in the content of
      malondialdehyde (MDA) (3.98 +/- 2.00 nmol ml-1) in serum. The two compounds
      showed strong capability for protective effects against cerebral damages induced
      by ischemia-reperfusion, and the protective effect may be related to the
      inhibition of lipid peroxidation. The use of the screening method based on
      tracing separation and ischemia reperfusion would provide a new way for detection
      of radical-scavenging and natural neuroprotective compounds from Swertia
      chirayita or complex matrices. 

PMID- 24013890
TI  - Comparative study concerning mistletoe viscotoxins antitumor activity.
AB  - Viscum album L. (Santalaceae) (VA) - a parasitic plant that grows on various
      trees - has proved a significant anticancer effect in both experimental studies
      and clinical trials. The present study assesses the influence of oxidative stress
      in mistletoe induced cytotoxicity in tumor cells, in relation to classic
      cytostatic therapy. VA ethanolic extract was administered alone and combined with
      doxorubicin (chloride) in Swiss female mice previously intraperitoneally (i.p.)
      inoculated with Ehrlich tumor cells (1 * 106/animal) that consequently developed
      Ehrlich ascites carcinoma (EAC). The administered doses were of 50 mg/kg on the
      1st, 3rd and 6th day for the VA extract, respectively of 2.5 mg/kg on the 1st and
      6th day for doxorubicin, after tumor cell implantation. Fourteen days later all
      mice were euthanized, ascites of the EAC were collected in order to analyze the
      tumor proliferation parameters, as well as blood samples, in order to evaluate
      the antioxidant status in plasma. Tumor development was associated with increased
      activity of plasma enzymes; classic doxorubicin therapy not only prevents the
      accumulation of ascitic fluid, but also significantly reduces the activity of
      plasma antioxidant enzymes. Furthermore, in association with VA extract, the
      protective effect is improved. Oxidative changes in Ehrlich tumor cells consisted
      in decreased catalase activity and amplified xanthine oxidase and peroxidase
      activities. 

PMID- 24013891
TI  - Body mass related variations in the polar lipid fatty acyl chain composition of
      the mammalian lung and alveolar surfactant.
AB  - In nine mammalian species (mouse - cattle: 21.5 g-503 kg) lung total
      phospholipids (PL), alveolar surfactant phosphatidylcholine (PC) and
      sphingomyelin (SM) fatty acyl (FA) chain composition was tested relating to body
      mass (BM) and resting respiratory rate (RRR) associated adaptations. In PL, PC
      and SM oleic acid (C18:1 n9) provided negative correlations with RRR. Palmitic
      acid (C16:0) was strongly, positively correlated with RRR in the pulmonary PLs,
      and myristic (C14:0) acid correlated positively with RRR in the surfactant PCs.
      In pulmonary PLs negative allometry was found for myristic, palmitic, palmitoleic
      (C16:1 n7) and docosahexaenoic (C22:6 n3) acids and total saturation, while oleic
      (C18:1 n9), alpha-linolenic (C18:3 n3) and gondoic (C20:1 n9) acids, total n9 FA
      s and monounsaturation increased allometrically. In surfactant PC FA s palmitic
      acid provided negative, while oleic acid and monounsaturation positive allometry;
      the average FA chain length (ACL) was identical in all species. Surfactant SM FA
      composition was fully species independent for palmitic and arachidonic acids,
      total saturation, monounsaturation and ACL. The in vivo lipid peroxidation rate
      was species independent. The variability of lung PLs was consonant with the
      "membrane pacemakers theory", while surfactant PC composition was mostly related
      to RRR. 

PMID- 24013892
TI  - Stem fasciation in cacti and succulent species--tissue anatomy, protein pattern
      and RAPD polymorphisms.
AB  - Fasciated and normal stem segments of Opuntia microdasys, Opuntia cylindrica,
      Huernia primulina and Euphorbia lactea were collected from the same plant and
      compared for their anatomy, water relations and genetic variations. Anatomical
      differences in terms of thickness of cuticle, vascular bundle, xylem and phloem
      were analyzed in both normal and fasciated stems. The mucilage cells were higher
      in the fasciated form of Opuntia microdasys than that in the normal form. Water
      status in terms of total water content (TWC), water deficit and relative water
      content (RWC) was influenced by fasciation. Genetic variations were tested in
      normal and fasciated stems using randomly amplified polymorphic DNA (RAPD)
      fingerprints and SDS-PAGE of soluble protein extracts. SDS-PAGE protein and RAPD
      analysis confirmed that normal and fasciated tissues were genetically different.
      Polymerase chain reaction (PCR) yielded different polymorphic banding patterns
      that were unique to each primer and distinguishable over all samples. The PCR
      results of normal and fasciated samples were significantly different in cases of
      primers P1, P2 and P3. These results indicate that occurrence of fasciation in
      Opuntia microdasys, Opuntia cylindrica, Huernia primulina and Euphorbia lactea is
      an epigenetic mutation of tissues. 

PMID- 24013893
TI  - Ultrastructure of central cell in female gametophyte of Castilleja wightii Elmer
      (Scrophulariaceae).
AB  - Embryo sac cells are highly differentiated in plants. The central cell is one of
      the most important cells of the embryo sac. It forms endosperm by fusion with a
      sperm cell. Ultrastructure of the central cell in the mature embryo sac of
      Castilleja wightii was investigated in this study. Nucleolus which had a lot of
      vacuole in a large secondary nucleus and numerous dictyosomes, vesicles,
      mitochondria, amyloplasts in cytoplasm were seen in this cell. Also free
      ribosomes in the form of polysomes and large lipid bodies were detected in the
      cytoplasm. Numerous vacuoles of different size were observed and some of them had
      autophagic function. Both smooth and rough endoplasmic reticulums were seen.
      Although invaginations were seen in the plasmalemma of the central cell to the
      inside of the embryo sac, a thick cuticular layer was observed outer side on the
      cell wall. The aim of this study was to contribute studies about the
      ultrastructure of embryo sacs. 

PMID- 24013894
TI  - Cell wall degradation and the dynamic changes of Ca2+ and related enzymes in the
      developing aerenchyma of wheat (Triticum aestivum L.) under waterlogging.
AB  - This research was aimed to study the cell wall degradation and the dynamic
      changes of Ca2+ and related enzymes in developing aerenchyma of wheat root under
      waterlogging. An examination of morphological development by light and electron
      microscope revealed that the structure of cell wall in middle cortical cells
      remained intact after 12 h of waterlogging and turned thinner after waterlogging
      for 24 h. At 48 h, the aerenchyma has been formed. The cellulase activity
      gradually increased in middle cortical cells within 24 h of waterlogging, and
      decreased with the formation of aerenchyma. Fluorescence detection and
      subcellular localization of Ca2+ showed the dynamic changing of Ca2+ at the
      cellular and subcellular levels during the development of aerenchyma. The
      activity of Ca2+-ATPase enhanced markedly in intercellular space, plasma membrane
      and tonoplast of some middle cortical cells after 8 h of waterlogging and
      remained high after 24 h, but it decreased after 48 h of waterlogging. All these
      suggests that cellulase, Ca2+ and Ca2+-ATPase show a dynamic distribution during
      the aerenchyma development which associated with the cell wall degradation of
      middle cortical cells. Moreover, there is a feedback regulation between Ca2+ and
      Ca2+-ATPase. 

PMID- 24013895
TI  - Oxidative stress in leaves of two olive cultivars under freezing conditions.
AB  - Olive is one of the most important cultivated Mediterranean plants. In order to
      determine the differences in frost resistance of two, two-year-old olive
      cultivars (Olea europaea cv. Leccino and cv. Oblica) growing on different types
      of nutrient substrates (soil and coconut fibres), the trees were exposed to low
      temperature (-5  degrees C) in the dark. It was shown that low temperature caused
      an increase in H2O2 concentration, level of lipid peroxidation and carbonyl
      protein content in both cultivars and on both nutrient substrates, respectively.
      The CAT and APX activities significantly varied depending on the cultivar, the
      nutrient substrate type and the time of exposure to low temperature. Cv. Oblica
      and cv. Leccino growing on coconut fibres showed a better antioxidative response
      to low temperature probably due to the higher nitrogen and phosphorus
      concentration established in this type of nutrient substrate. That positive
      antioxidative response determined on coconut fibres was more pronounced in leaves
      of cv. Leccino. 

PMID- 24013896
TI  - Variability of stomata and 45S and 5S rDNAs loci characteristics in two species
      of Anthoxanthum genus: A. aristatum and A. odoratum (Poaceae).
AB  - Diploid Anthoxanthum odoratum and tetraploid A. aristatum were compared with
      respect to stomatal guard cell lengths, and stomatal density at adaxial and
      abaxial surfaces of the lamina. Further, the genome size of both species was
      determined by flow cytometry, and the number as well as the chromosomal
      distribution of 5S and 45S rDNAs were examined using FISH with ribosomal DNA
      (rDNA) probes. The average length of stomatal guard cells in A. odoratum was
      shown to be greater than that for A. aristatum, but the ranges overlapped.
      Moreover, reduction in stomatal frequency was found at higher ploidy levels.The
      genome size was 6.863 pg/2C DNA for A. aristatum and 13.252 pg/2C DNA for A.
      odoratum. A. aristatum has four sites of 5S rDNA in its root-tip meristematic
      cells, whereas A. odoratum has six. Both species have six sites of 45S rDNA.
      Chromosomal localization of the rDNA varied, which suggests that chromosome
      rearrangements took place during Anthoxanthum genome evolution. 

PMID- 24013897
TI  - Phytohormone and assimilate profiles in emasculated flowers of the black locust
      (Robinia pseudoacacia) during development.
AB  - Emasculation and bagging of flowers, which are widely used in the controlled
      pollination of monoclinous plants, may induce premature senescence, flower
      abscission and low fruit set. To determine the mechanism responsible for these
      phenomena, levels of abscisic acid (ABA), jasmonic acid (JA), indole-3-acetic
      acid (IAA), ethylene, soluble sugars, reducing sugars and free amino acids in
      black locust (Robinia pseudoacacia) flowers subjected to different treatments
      were quantified at different developmental stages. The phytohormones and
      assimilates were also quantified in untreated flowers to investigate the presence
      of discernible patterns. The levels of ethylene and ABA in emasculated and bagged
      (EB) flowers increased prematurely compared with those of untreated flowers,
      whereas the content of reducing sugars in EB flowers decreased compared with that
      of untreated flowers. These results indicated that the premature increase in
      ethylene and ABA synthesis, and the decrease in reducing sugars content, in EB
      flowers may cause flower abscission and result in low fruit set, which may be
      relevant for assimilate applications and future research on the regulation of
      controlled pollinations with exogenous phytohormones. 

PMID- 24013898
TI  - Pre-culturing of nodal explants in thidiazuron supplemented liquid medium
      improves in vitro shoot multiplication of Cassia angustifolia.
AB  - An in vitro propagation system for Cassia angustifolia Vahl. has been developed.
      Due to the presence of sennosides, the demand of this plant has increased
      manyfold in global market. Multiple shoots were induced by culturing nodal
      explants excised from mature plants on a liquid Murashige and Skoog [8] medium
      supplemented with 5-100 MUM of thidiazuron (TDZ) for different treatment duration
      (4, 8, 12 and 16 d). The optimal level of TDZ supplemented to the culture medium
      was 75 MUM for 12 d induction period followed by subculturing in MS medium devoid
      of TDZ as it produced maximum regeneration frequency (87%), mean number of shoots
      (9.6 +/- 0.33) and shoot length (4.4 +/- 0.46 cm) per explant. A culture period
      longer than 12 d with TDZ resulted in the formation of fasciated or distorted
      shoots. Ex vitro rooting was achieved when the basal cut end of regenerated
      shoots was dipped in 200 MUM indole-3-butyric acid (IBA) for half an hour
      followed by their transplantation in plastic pots filled with sterile soilrite
      where 85% plantlets grew well and all exhibited normal development. The present
      findings describe an efficient and rapid plant regeneration protocol that can
      further be used for genetic transformation studies. 

PMID- 24013899
TI  - Effect of submerged and solid-state fermentation on pigment and citrinin
      production by Monascus purpureus.
AB  - Monascus pigments, which are produced by various species of Monascus, often have
      been used as a natural colourant and as traditional natural food additives,
      especially in Southern China, Japan and Southeastern Asia. The limitation of wide
      using Monascus pigment is attributed to one of its secondary metabolites named
      citrinin. The aim of this study was to investigate the influence of pigment and
      citrinin production via submerged fermentation (SmF) and solid-state fermentation
      (SF) from rice (Oryza sativa L.) by Monascus purpureus AS3.531. The optimal
      fermentation temperature and pH were significantly different for pigment
      production through different fermentation mode (35  degrees C, pH 5.0 for SF and
      32  degrees C, pH 5.5 for SmF, respectively). Adding 2% (w/v) of glycerol in the
      medium could enhance the pigment production. On the optimized condition, although
      the concentration of citrinin produced by SmF (19.02 ug/g) increased more than
      100 times than that by SF (0.018 ug/g), the pigment yield by SmF (7.93 U/g/g)
      could be comparable to that by SF (6.63 U/g/g). Those indicate us that
      fermentation mode seems to be the primary factor which influence the citrinin
      yield and secondary factor for pigment production. 

PMID- 24013900
TI  - Lymph node counts and ratio in axillary dissections following neoadjuvant
      chemotherapy for breast cancer: a better alternative to traditional pN staging.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NCT) for breast cancer might change the
      number of involved and detected nodes in axillary lymph node dissections (ALND).
      In this study, we analyzed whether the number of dissected nodes and the lymph
      node ratio (LNR, defined as the proportion of involved nodes in dissected nodes)
      would have a better prognostic value than traditional pN staging. METHODS: A
      total of 569 patients with stage II, III breast cancer were included in this
      retrospective study. All patients underwent a median of three cycles of NCT
      followed by mastectomy and ALND. Clinical and pathological variables were
      investigated using univariate and multivariate survival analyses. RESULTS: In
      post-NCT node-negative (LN-) patients, those with 4-9 dissected nodes experienced
      a significantly lower relapse-free survival (RFS) compared with those with 10 or
      more dissected nodes (hazard ratio = 0.19, 0.41, for 10-19 nodes, 20+ nodes,
      respectively; 4-9 nodes as the reference; P = 0.002). In post-NCT node-positive
      (LN+) patients, a lower LNR was correlated with a better RFS on multivariate
      analysis, and pN staging failed to show independent prognostic significance when
      the LNR was included in the Cox regression model (hazard ratio = 4.2, 2.97, 2.24,
      and 1.68 for LNR 81-100, 61-80, 41-60; and 21-40 %, respectively; LNR 0-20 % as
      the reference. P < 0.001). In addition, there were significant differences in the
      estimated 5-year RFS for pN1 (P = 0.043) and pN3 patients (P = 0.03) among the
      different LNR subgroups. CONCLUSIONS: Our study has provided new evidence that
      the number of dissected nodes (in LN- patients) and the LNR (in LN+ patients)
      might be a complementary or alternative method to traditional pN staging when
      evaluating disease after primary treatment.

PMID- 24013902
TI  - Dimensional weighting in cross-dimensional singleton conjunction search.
AB  - In order to efficiently deploy our limited visual processing resources, we must
      decide what information is relevant and to be prioritized and what information
      should rather be ignored. To detect visual information that we know is relevant
      but that is not very salient, we need to set our system to prioritize and combine
      information from different visual dimensions (e.g., size, color, motion). Four
      experiments examined the allocation of processing resources across different
      visual dimensions when observers searched for a singleton target defined by a
      conjunction of size (primary dimension: the target was always large) with either
      color or motion (secondary dimension: variable across trials) within
      heterogeneously sized, colored, and moving distractors. The results revealed
      search reaction times to be substantially increased in a given trial in which the
      secondary target dimension was changed from the preceding trial--indicative of a
      suboptimal distribution of dimensional weights carried over from the previous
      trial and of attentional weight being bound by the (need to filter within the)
      primary dimension, thereby reducing the weight available for processing the
      secondary dimensions. Semantic precueing of the secondary dimension and visual
      marking of the search-irrelevant items in the primary dimension reduced these
      costs significantly. However, observers were limited in their ability to
      implement both top-down sets simultaneously. These findings argue in favor of a
      parallel distribution of dimensional processing resources across multiple visual
      dimensions and, furthermore, that visual marking releases attentional weight
      bound to the primary dimension, thus permitting more efficient (parallel)
      processing in the secondary dimensions.

PMID- 24013903
TI  - Phosphorylation and externalization of galectin-4 is controlled by Src family
      kinases.
AB  - Galectin-4 is a cytosolic protein that lacks a signal sequence but is
      externalized and binds to 3-O-sulfated glycoconjugates extracellularly. The
      mechanism of subcellular localization and externalization of galectin-4 has not
      yet been determined. A preliminary experiment using pervanadate (PV) showed that
      galectin-4 is tyrosine-phosphorylated in cells and suggested that Src kinases are
      involved. Cell transfection with galectin-4 and active Src plasmids showed that
      galectin-4 can be tyrosine phosphorylated by members of the Src kinase family.
      The C-terminal peptide YVQI of galectin-4 was found to play an important role in
      its tyrosine phosphorylation, and the SH2 domains of Src and SHP2 were found to
      bind to this peptide. Immunofluorescence analysis showed that galectin-4 and
      phosphorylated proteins were intensely stained in the area of membrane
      protrusions of PV-treated or Src-activated cells. Furthermore, MUC1 derived from
      NUGC-4 cells was observed to bind to galectin-4, and externalization of the bound
      molecules from the cell to the medium increased in the hyperphosphorylated
      condition. Study of the transfection of the mutant galectin-4 which lacks the C
      terminal peptide revealed that the phosphorylation status is important for
      externalization of galectin-4. These results suggest that externalization of
      galectin-4 can be regulated by signaling molecules and that it may function
      intracellularly as an adaptor protein serving to modulate the trafficking of
      glycoproteins. 

PMID- 24013901
TI  - Increased systemic Th17 cytokines are associated with diastolic dysfunction in
      children and adolescents with diabetic ketoacidosis.
AB  - Diastolic dysfunction suggestive of diabetic cardiomyopathy is established in
      children with T1DM, but its pathogenesis is not well understood. We studied the
      relationships of systemic inflammatory cytokines/chemokines and cardiac function
      in 17 children with T1DM during and after correction of diabetic ketoacidosis
      (DKA). Twenty seven of the 39 measured cytokines/chemokines were elevated at 6-12
      hours into treatment of DKA compared to values after DKA resolution. Eight
      patients displayed at least one parameter of diastolic abnormality (DA) during
      acute DKA. Significant associations were present between nine of the
      cytokine/chemokine levels and the DA over time. Interestingly, four of these nine
      interactive cytokines (GM-CSF, G-CSF, IL-12p40, IL-17) are associated with a Th17
      mediated cell response. Both the DA and CCL7 and IL-12p40, had independent
      associations with African American patients. Thus, we report occurrence of a
      systemic inflammatory response and the presence of cardiac diastolic dysfunction
      in a subset of young T1DM patients during acute DKA. 

PMID- 24013904
TI  - Phase II trial of capecitabine and everolimus (RAD001) combination in refractory
      gastric cancer patients.
AB  - BACKGROUND: The aim of this study was to assess the efficacy and safety of
      combination regimen of capecitabine plus everolimus in patients with refractory
      gastric cancer who have failed to at least two cytotoxic regimens. METHODS:
      Patients received capecitabine 650 mg/m(2) twice daily (D1-14) and everolimus 5
      mg twice daily (D1-21) every 3 weeks until disease progression or unacceptable
      toxicity. The primary endpoint of the study was overall response (partial or
      complete response) and the secondary endpoints were progression-free survival
      (time between registration and disease progression or death) and overall
      survival. Pharmacokinetic analysis was also performed. Patients who have failed
      to at least two cytotoxic regimens were enrolled. RESULTS: Between March 2010 and
      June 2012, 47 patients were enrolled. 33 patients (70.2%) had received more than
      three previous regimens prior to enrolment. Among 43 evaluable patients for
      treatment response, 5 patients achieved confirmed partial response and 18
      patients showed stable disease, resulting in an overall response rate (ORR) of
      10.6% (95% C.I.: 1.8-19.4%) and disease control rate of 48.9% (95% C.I.:34.6
      63.2%). At a median follow-up of 106 weeks (range, 21-141 weeks), the median
      progression-free survival and overall survival were 11.0 weeks (95% C.I.: 5.7
      16.3 weeks) and 21.0 weeks (95% C.I.: 14.3-27.7 weeks), respectively. Grade 3
      nausea, diarrhea and stomatitis occurred in two, three and three patients,
      respectively. Elevated liver enzyme was observed in 21 patients and no patient
      had pulmonary fibrosis. CONCLUSIONS: The combination of capecitabine 650 mg/m(2)
      twice daily and everolimus 5 mg twice daily was found to be effective in a small
      subset of GC patients who were heavily pre-treated.

PMID- 24013905
TI  - Circadian clock regulation of the cell cycle in the zebrafish intestine.
AB  - The circadian clock controls cell proliferation in a number of healthy tissues
      where cell renewal and regeneration are critical for normal physiological
      function. The intestine is an organ that typically undergoes regular cycles of
      cell division, differentiation and apoptosis as part of its role in digestion and
      nutrient absorption. The aim of this study was to explore circadian clock
      regulation of cell proliferation and cell cycle gene expression in the zebrafish
      intestine. Here we show that the zebrafish gut contains a directly light
      entrainable circadian pacemaker, which regulates the daily timing of mitosis.
      Furthermore, this intestinal clock controls the expression of key cell cycle
      regulators, such as cdc2, wee1, p21, PCNA and cdk2, but only weakly influences
      cyclin B1, cyclin B2 and cyclin E1 expression. Interestingly, food deprivation
      has little impact on circadian clock function in the gut, but dramatically
      reduces cell proliferation, as well as cell cycle gene expression in this tissue.
      Timed feeding under constant dark conditions is able to drive rhythmic expression
      not only of circadian clock genes, but also of several cell cycle genes,
      suggesting that food can entrain the clock, as well as the cell cycle in the
      intestine. Rather surprisingly, we found that timed feeding is critical for high
      amplitude rhythms in cell cycle gene expression, even when zebrafish are
      maintained on a light-dark cycle. Together these results suggest that the
      intestinal clock integrates multiple rhythmic cues, including light and food, to
      function optimally. 

PMID- 24013907
TI  - Heterogeneity and hypothesis testing in neuropsychiatric illness.
AB  - The confounding effects of heterogeneity in biological psychiatry and psychiatric
      genetics have been widely discussed in the literature. We suggest an approach in
      which heterogeneity may be put to use in hypothesis testing and may find
      application in evaluation of the Crespi and Badcock (C&B) imprinting hypothesis.
      Here we consider three potential sources of etiologic subtypes for analysis.

PMID- 24013906
TI  - Magnitude representations in Williams syndrome: differential acuity in time,
      space and number processing.
AB  - For some authors, the human sensitivity to numerosities would be grounded in our
      ability to process non-numerical magnitudes. In the present study, the
      developmental relationships between non numerical and numerical magnitude
      processing are examined in people with Williams syndrome (WS), a genetic disorder
      known to associate visuo-spatial and math learning disabilities. Twenty patients
      with WS and 40 typically developing children matched on verbal or non-verbal
      abilities were administered three comparison tasks in which they had to compare
      numerosities, lengths or durations. Participants with WS showed lower acuity
      (manifested by a higher Weber fraction) than their verbal matched peers when
      processing numerical and spatial but not temporal magnitudes, indicating that
      they do not present a domain-general dysfunction of all magnitude processing.
      Conversely, they do not differ from non-verbal matched participants in any of the
      three tasks. Finally, correlational analyses revealed that non-numerical and
      numerical acuity indexes were both related to the first mathematical acquisitions
      but not with later arithmetical skills. 

PMID- 24013908
TI  - Space versus Place in Complex Human-Natural Systems: Spatial and Multi-level
      Models of Tropical Land Use and Cover Change (LUCC) in Guatemala.
AB  - The relative role of space and place has long been debated in geography. Yet
      modeling efforts applied to coupled human-natural systems seemingly favor models
      assuming continuous spatial relationships. We examine the relative importance of
      placebased hierarchical versus spatial clustering influences in tropical land
      use/cover change (LUCC). Guatemala was chosen as our study site given its high
      rural population growth and deforestation in recent decades. We test predictors
      of 2009 forest cover and forest cover change from 2001-2009 across Guatemala's
      331 municipalities and 22 departments using spatial and multi-level statistical
      models. Our results indicate the emergence of several socio-economic predictors
      of LUCC regardless of model choice. Hierarchical model results suggest that
      significant differences exist at the municipal and departmental levels but
      largely maintain the magnitude and direction of single-level model coefficient
      estimates. They are also intervention-relevant since policies tend to be
      applicable to distinct political units rather than to continuous space. Spatial
      models complement hierarchical approaches by indicating where and to what
      magnitude significant negative and positive clustering associations emerge.
      Appreciating the comparative advantages and limitations of spatial and nested
      models enhances a holistic approach to geographical analysis of tropical LUCC and
      human-environment interactions.

PMID- 24013909
TI  - Mechanical design and performance specifications of anthropomorphic prosthetic
      hands: a review.
AB  - In this article, we set forth a detailed analysis of the mechanical
      characteristics of anthropomorphic prosthetic hands. We report on an empirical
      study concerning the performance of several commercially available myoelectric
      prosthetic hands, including the Vincent, iLimb, iLimb Pulse, Bebionic, Bebionic
      v2, and Michelangelo hands. We investigated the finger design and kinematics,
      mechanical joint coupling, and actuation methods of these commercial prosthetic
      hands. The empirical findings are supplemented with a compilation of published
      data on both commercial and prototype research prosthetic hands. We discuss
      numerous mechanical design parameters by referencing examples in the literature.
      Crucial design trade-offs are highlighted, including number of actuators and hand
      complexity, hand weight, and grasp force. Finally, we offer a set of rules of
      thumb regarding the mechanical design of anthropomorphic prosthetic hands. 

PMID- 24013910
TI  - Load applied on bone-anchored transfemoral prosthesis: characterization of a
      prosthesis-a pilot study.
AB  - The objectives of this study were to (1) record the inner-prosthesis loading
      during activities of daily living (ADLs), (2) present a set of variables
      comparing loading data, and (3) provide an example of characterization of two
      prostheses. The load was measured at 200 Hz using a multi-axial transducer
      mounted between the residuum and the knee of an individual with unilateral
      transfemoral amputation fitted with a bone-anchored prosthesis. The load was
      measured while using two different prosthetic knees, mechanical (PRO1) and micro
      processor-controlled (PRO2), during six ADLs. The characterization of the
      prostheses was achieved using a set of variables split into four categories,
      including temporal characteristics, maximum loading, loading slopes, and impulse.
      Approximately 360 gait cycles were analyzed for each prosthesis. PRO1 showed a
      cadence improved by 19% and 7%, a maximum force on the long axis reduced by 11%
      and 19%, and an impulse reduced by 32% and 15% during descent of incline and
      stairs compared with PRO2, respectively. This work confirmed that the proposed
      apparatus and characterization can reveal how changes of prosthetic components
      are translated into inner-prosthetic loading. 

PMID- 24013911
TI  - Cardiometabolic risk factors in Iranians with spinal cord injury: analysis by
      injury-related variables.
AB  - Persons with spinal cord injury (SCI) have a high prevalence of abnormalities in
      carbohydrate and lipid metabolism. These abnormalities cause adverse coronary
      heart disease (CHD) in patients with SCI. In this study, we performed a detailed
      analysis of the level-specific cardiometabolic risk factors in individuals with
      SCI and analyzed the association of injury level on these risk factors. This was
      a cross-sectional study of 162 patients with SCI, assessing the prevalence of
      diabetes mellitus, dyslipidemia, hypertension, obesity, and smoking. Fasting
      blood sugar (>100) was diagnosed in 27 patients (16.7%). Of the total patients,
      36 (22.2%) had a total cholesterol (TC) level of >200. A triglyceride level of
      >150 was present in 56 patients (34.6%). Hypertension was present in 2.5% of the
      entire patient group. Body mass index (BMI), TC, and low-density lipoprotein
      cholesterol (LDL-C) were significantly higher in the paraplegia group than the
      tetraplegia group (24.44 +/- 4.23 vs 22.65 +/- 4.27, p = 0.01; 185.71 +/- 40.69
      vs 163.28 +/- 37.92, p < 0.001; and 102.51 +/- 28.20 vs 89.15 +/- 22.35, p =
      0.01, respectively). Patients with paraplegia may have increased hypertension,
      higher BMI, and increasing levels of serum LDL-C and TC than those with
      tetraplegia. Conventional risk factors for CHD should be identified and treated
      in individuals with SCI. 

PMID- 24013912
TI  - Internet-based physical assessment of people with Parkinson disease is accurate
      and reliable: a pilot study.
AB  - Telerehabilitation may be an alternative service delivery model for people with
      Parkinson disease (PD) who live in areas where traditional rehabilitation
      services are not readily accessible. The aim of this study was to determine the
      accuracy and reliability of performing remote physical assessments of people with
      PD via telerehabilitation when compared with traditional face-to-face
      assessments. Twelve subjects were simultaneously examined by a face-to-face
      investigator and a remote investigator via the eHAB telerehabilitation system.
      The outcome measures evaluated included the timed stance test, Timed "Up and Go"
      test, step test, steps in 360 degree turn, Berg Balance Scale, and lateral and
      functional reach tests. Limits of agreements intervals and weighted kappa
      statistics demonstrated the telerehabilitation assessments to be accurate within
      clinically acceptable limits. A high level of inter- and intrarater reliability
      was demonstrated across all telerehabilitation assessments. This study indicates
      that it is possible to assess the physical ability of people with PD via
      telerehabilitation systems and provides support for the further development of
      telerehabilitation applications for patients with neurological disorders. 

PMID- 24013913
TI  - Coordination patterns of shoulder muscles during level-ground and incline
      wheelchair propulsion.
AB  - The aim of this study was to investigate how the coordination patterns of
      shoulder muscles change with level-ground and incline wheelchair propulsion.
      Wheelchair kinetics and electromyography (EMG) activity of seven muscles were
      recorded with surface electrodes for 15 nondisabled subjects during wheelchair
      propulsion on a stationary ergometer and wooden ramp (4 degree slope). Kinetic
      data were measured by a SmartWheel. The kinetics variables and the onset,
      cessation, and duration of EMG activity from seven muscles were compared with
      paired t-tests for two sessions. Muscle coordination patterns across seven
      muscles were analyzed by principal component analysis. Push forces on the push
      rim and the percentage of push phase in the cycle increased significantly during
      incline propulsion. Propulsion condition and posture affected muscle coordination
      patterns. During incline propulsion, there was more intense and longer EMG
      activity of push muscles in the push phase and less EMG activity of the recovery
      muscles, which corresponded with the increased kinetic data total force output
      and longer push phase in the incline condition. This work establishes a framework
      for developing a performance feedback system for wheelchair users to better
      coordinate their muscle patterning activity. 

PMID- 24013914
TI  - Veterans Health Administration vocational services for Operation Iraqi
      Freedom/Operation Enduring Freedom Veterans with mental health conditions.
AB  - High rates of mental health conditions and unemployment are significant problems
      facing Veterans of Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF).
      We examined two national Veterans Health Administration (VHA) databases from
      fiscal years 2008-2009: a larger database (n = 75,607) of OIF/OEF Veterans with
      posttraumatic stress disorder, depression, substance use disorder, or traumatic
      brain injury (TBI) and a smaller subset (n = 1,010) of those Veterans whose
      employment was tracked during their participation in VHA vocational services.
      Only 8.4% of Veterans in the larger database accessed any vocational services and
      retention was low, with most Veterans attending one or two appointments. Veterans
      with TBI and with more mental health conditions overall were more likely to
      access vocational services. Only 2.2% of Veterans received evidence-based
      supported employment. However, supported employment was effective, with 51% of
      those Veterans receiving it obtaining competitive work. Effect sizes quantifying
      the effect of supported employment provision on competitive work attainment,
      number of jobs, job tenure, and retention in vocational services were large.
      Given the high success rate of supported employment for these Veterans,
      additional supported employment specialists for this population would be expected
      to improve work outcomes for post-9/11 Veterans who want assistance returning to
      work. 

PMID- 24013915
TI  - Prosthesis preference is related to stride-to-stride fluctuations at the
      prosthetic ankle.
AB  - The purpose of this study was to determine the relationship between stride-to
      stride fluctuations and prosthesis preference. Thirteen individuals with
      unilateral, transtibial amputation consented to participate. Individuals walked
      on a treadmill for 3 min with their prescribed and an alternate prosthesis.
      Stride-to-stride fluctuations were quantified with the largest Lyapunov exponent
      (LyE) of each joint flexion/extension time series. The change in the LyE was
      calculated for each major lower-limb joint for both conditions. Participants
      indicated preference between the prostheses on a continuous visual analog scale.
      The change in the LyE was correlated with the degree of preference between the
      two prostheses at the prosthetic ankle. The change in the LyE of the prosthetic
      ankle was strongly related to the degree of preference (r = 0.629, p = 0.02).
      Thus, stride-to-stride fluctuations, quantified by the LyE, are strongly related
      to the patient's perception of the prosthesis. As a result, the LyE is the first
      objective measure to detect changes in gait that relate to the patient's
      perception of the prosthesis. The LyE should be further examined as a potentially
      effective prescriptive and outcome measure in prosthetic rehabilitation. 

PMID- 24013916
TI  - Motor control and learning with lower-limb myoelectric control in amputees.
AB  - Advances in robotic technology have recently enabled the development of powered
      lower-limb prosthetic limbs. A major hurdle in developing commercially successful
      powered prostheses is the control interface. Myoelectric signals are one way for
      prosthetic users to provide feedforward volitional control of prosthesis
      mechanics. The goal of this study was to assess motor learning in people with
      lower-limb amputation using proportional myoelectric control from residual-limb
      muscles. We examined individuals with transtibial amputation and nondisabled
      controls performing tracking tasks of a virtual object. We assessed how quickly
      the individuals with amputation improved their performance and whether years
      since amputation correlated with performance. At the beginning of training,
      subjects with amputation performed much worse than control subjects. By the end
      of a short training period, tracking error did not significantly differ between
      subjects with amputation and nondisabled subjects. Initial but not final
      performance correlated significantly with time since amputation. This study
      demonstrates that although subjects with amputation may initially have poor
      volitional control of their residual lower-limb muscles, training can
      substantially improve their volitional control. These findings are encouraging
      for the future use of proportional myoelectric control of powered lower-limb
      prostheses. 

PMID- 24013917
TI  - Effects of cognitive task on gait initiation in Parkinson disease: evidence of
      motor prioritization?
AB  - While much is known about the effects of dual tasking on cyclical and continuous
      motor performance (e.g., locomotion), there is a paucity of information on the
      effect of dual tasking on the initiation of movement. Therefore, the purpose of
      this study was to investigate the effect of a concurrent cognitive task on gait
      initiation in three groups: patients with Parkinson disease, healthy older
      adults, and healthy young adults. We examined the anticipatory postural
      adjustment displacements and velocities during single-task gait initiation as
      well as two dual-task conditions: (1) 0-back + gait initiation and (2) 2-back +
      gait initiation. The Parkinson disease group exhibited less anticipatory postural
      adjustment displacement and velocity than their aged-matched healthy peers and
      young adults during the single- and dual-task gait initiation settings (p <
      0.05). Of interest was the finding of no additional effect on anticipatory
      postural adjustment displacement or velocity of gait initiation during the dual
      task conditions in any group, including the Parkinson disease group. More
      traditionally studied gait/balance dual-task paradigms have demonstrated both
      motor and cognitive decline. Therefore, our results may suggest a prioritization
      of more "intentional" movement task (e.g., gait initiation) while dual tasking in
      Parkinson disease. 

PMID- 24013919
TI  - Comparison of mechanical properties of silicone and PVC (polyvinylchloride)
      cosmetic gloves for articulating hand prostheses.
AB  - Current articulating electric and body-powered hands have a lower pinch force (15
      34 N) than electric hands with stiff fingers (55-100 N). The cosmetic glove,
      which covers a hand prosthesis, negatively affects the mechanical efficiency of a
      prosthesis. The goal of this study is to mechanically compare polyvinylchloride
      (PVC) and silicone cosmetic gloves and quantify the stiffness of the finger
      joints, the required actuation energy, and the energy dissipation during joint
      articulation. Six cosmetic gloves, identical in size but made from different
      materials, were mechanically tested: three PVC and three silicone. The silicone
      gloves required less work and dissipated less energy during flexing. They also
      had a lower joint stiffness and required a lower maximum joint torque. Based on
      energy requirements, joint stiffness, and required joint torque, the tested
      silicone glove is most suitable for application on an articulating hand
      prosthesis. 

PMID- 24013918
TI  - New method of fixation of in-bone implanted prosthesis.
AB  - This article presents results on the effectiveness of a new version of the
      titanium porous composite skin and bone integrated pylon (SBIP). The SBIP is
      designed for direct skeletal attachment of limb prostheses and was evaluated in a
      preclinical study with three rabbits. In accordance with the study protocol, a
      new version of the pylon (SBIP-3) was implanted into the hind leg residuum of
      three rabbits. The SBIP-3 has side fins that are designed to improve the bond
      between the bone and pylon. The fins are positioned inside two slots precut in
      the bone walls; their length can be adjusted to match the thickness of the bone
      walls. After 13 (animal 1) or 26 (animals 2 and 3) wk, the animals were
      sacrificed and samples collected for histopathological analysis. The space
      between the fins and the bone into which they were fit was filled with
      fibrovascular tissue and woven bone. No substantial inflammation was found. We
      suggest that if further studies substantiate the present results, the proposed
      method can become an alternative to the established technique of implanting
      prostheses into the medullary canal of the hosting bone. 

PMID- 24013920
TI  - Healthcare provider beliefs about exercise and fatigue in people with multiple
      sclerosis.
AB  - This study describes the experiences of four groups of healthcare providers who
      facilitate exercise interventions for people with multiple sclerosis (MS)-related
      fatigue. Fatigue is a complex symptom frequently experienced by people with MS,
      yet it is poorly understood by clinicians and clinical researchers. Historically,
      clinicians have recommended less physical activity in order to limit fatigue;
      however, recent experimental studies suggest that regular exercise provides
      health benefits with little increase in fatigue. We used interpretive description
      methodology to guide data collection and analysis. Four groups of healthcare
      providers participated in either focus group discussions or individual
      interviews. Transcripts were analyzed for key meanings. Healthcare providers
      described their perceptions of the "nature of fatigue" and how this raised
      "professional challenges," specifically "barriers to implementation" of
      interventions, "stirring conflict" among interdisciplinary members, and
      "modifying roles." The nature of fatigue and professional challenges influenced
      clinician practice by "demanding creativity" with regard to exercise prescription
      and advice. Healthcare providers are encouraged to consider strategies of active
      listening and careful observation when providing individualized exercise programs
      for people with MS-related fatigue. In addition, recognition and understanding of
      the complex nature of fatigue by the interdisciplinary team might facilitate more
      positive exercise experiences for this population. 

PMID- 24013921
TI  - The CK2 kinase stabilizes CLOCK and represses its activity in the Drosophila
      circadian oscillator.
AB  - Phosphorylation is a pivotal regulatory mechanism for protein stability and
      activity in circadian clocks regardless of their evolutionary origin. It
      determines the speed and strength of molecular oscillations by acting on
      transcriptional activators and their repressors, which form negative feedback
      loops. In Drosophila, the CK2 kinase phosphorylates and destabilizes the PERIOD
      (PER) and TIMELESS (TIM) proteins, which inhibit CLOCK (CLK) transcriptional
      activity. Here we show that CK2 also targets the CLK activator directly.
      Downregulating the activity of the catalytic alpha subunit of CK2 induces CLK
      degradation, even in the absence of PER and TIM. Unexpectedly, the regulatory
      beta subunit of the CK2 holoenzyme is not required for the regulation of CLK
      stability. In addition, downregulation of CK2alpha activity decreases CLK
      phosphorylation and increases per and tim transcription. These results indicate
      that CK2 inhibits CLK degradation while reducing its activity. Since the CK1
      kinase promotes CLK degradation, we suggest that CLK stability and
      transcriptional activity result from counteracting effects of CK1 and CK2.

PMID- 24013922
TI  - Risk factors associated with preterm delivery after fetoscopic laser ablation for
      twin-twin transfusion syndrome.
AB  - OBJECTIVE: Despite improved perinatal survival following fetoscopic laser
      ablation (FLA) for twin-twin transfusion syndrome (TTTS), prematurity remains an
      important contributor to perinatal mortality and morbidity. The objective of the
      study was to identify risk factors for complicated preterm delivery after FLA.
      METHODS: Retrospective cohort study of prospectively collected data on
      maternal/fetal demographics and pre-operative, operative and postoperative
      variables of 459 patients treated with FLA in three USA fetal centers.
      Multivariate linear regression was performed to identify significant risk factors
      associated with preterm delivery, which were cross-validated using the k-fold
      method. Multivariate logistic regression was performed to identify risk factors
      for early compared with late preterm delivery based on median gestational age at
      delivery of 32 weeks. RESULTS: There were significant differences in case
      selection and outcomes between the centers. After controlling for the center of
      surgery, multivariate analysis indicated that a lower maternal age at procedure,
      a history of previous prematurity, shortened cervical length, use of
      amnioinfusion, a cannula diameter of 12 French (Fr), lack of a collagen plug
      placement and iatrogenic preterm premature rupture of membranes (iPPROM) were
      significantly associated with a lower gestational age at delivery. CONCLUSIONS:
      Specific fetal/maternal and operative variables are associated with preterm
      delivery after FLA for the treatment of TTTS. Further studies to modify some of
      these variables may decrease the perinatal morbidity after laser therapy.

PMID- 24013924
TI  - Fluorescent azobenzenes and aromatic aldimines featuring an N-B interaction.
AB  - Azobenzenes are constituents of the commonly and widely used azo dyes. Many dyes,
      except for the azo dyes, have been utilized for fluorescent materials. However,
      there are only a few fluorescent azobenzene derivatives and their fluorescence
      efficiencies are quite low. The current perspective provides an account of the
      fluorescent azobenzenes and aromatic aldimines featuring an N-B interaction.
      Incorporation of the intramolecular N-B interaction by using the
      bis(pentafluorophenyl)boryl group makes the azobenzenes and aromatic aldimines
      fluorescent with a range of colours. Some of them fluoresce with extraordinarily
      high fluorescence quantum yields. Their synthesis, structures, fluorescence
      properties, and applications are discussed. 

PMID- 24013926
TI  - The Xeno-glycomics database (XDB): a relational database of qualitative and
      quantitative pig glycome repertoire.
AB  - SUMMARY: In recent years, the improvement of mass spectrometry-based glycomics
      techniques (i.e. highly sensitive, quantitative and high-throughput analytical
      tools) has enabled us to obtain a large dataset of glycans. Here we present a
      database named Xeno-glycomics database (XDB) that contains cell- or tissue
      specific pig glycomes analyzed with mass spectrometry-based techniques, including
      a comprehensive pig glycan information on chemical structures, mass values, types
      and relative quantities. It was designed as a user-friendly web-based interface
      that allows users to query the database according to pig tissue/cell types or
      glycan masses. This database will contribute in providing qualitative and
      quantitative information on glycomes characterized from various pig cells/organs
      in xenotransplantation and might eventually provide new targets in the alpha1,3
      galactosyltransferase gene-knock out pigs era. AVAILABILITY: The database can be
      accessed on the web at http://bioinformatics.snu.ac.kr/xdb.

PMID- 24013925
TI  - targetHub: a programmable interface for miRNA-gene interactions.
AB  - MOTIVATION: With the expansion of high-throughput technologies, understanding
      different kinds of genome-level data is a common task. MicroRNA (miRNA) is
      increasingly profiled using high-throughput technologies (microarrays or next
      generation sequencing). The downstream analysis of miRNA targets can be
      difficult. Although there are many databases and algorithms to predict miRNA
      targets, there are few tools to integrate miRNA-gene interaction data into high
      throughput genomic analyses. RESULTS: We present targetHub, a CouchDB database of
      miRNA-gene interactions. TargetHub provides a programmer-friendly interface to
      access miRNA targets. The Web site provides RESTful access to miRNA-gene
      interactions with an assortment of gene and miRNA identifiers. It can be a useful
      tool to integrate miRNA target interaction data directly into high-throughput
      bioinformatics analyses. AVAILABILITY: TargetHub is available on the web at
      http://app1.bioinformatics.mdanderson.org/tarhub/_design/basic/index.html.

PMID- 24013927
TI  - Multi-profile Bayesian alignment model for LC-MS data analysis with integration
      of internal standards.
AB  - MOTIVATION: Liquid chromatography-mass spectrometry (LC-MS) has been widely used
      for profiling expression levels of biomolecules in various '-omic' studies
      including proteomics, metabolomics and glycomics. Appropriate LC-MS data
      preprocessing steps are needed to detect true differences between biological
      groups. Retention time (RT) alignment, which is required to ensure that ion
      intensity measurements among multiple LC-MS runs are comparable, is one of the
      most important yet challenging preprocessing steps. Current alignment approaches
      estimate RT variability using either single chromatograms or detected peaks, but
      do not simultaneously take into account the complementary information embedded in
      the entire LC-MS data. RESULTS: We propose a Bayesian alignment model for LC-MS
      data analysis. The alignment model provides estimates of the RT variability along
      with uncertainty measures. The model enables integration of multiple sources of
      information including internal standards and clustered chromatograms in a
      mathematically rigorous framework. We apply the model to LC-MS metabolomic,
      proteomic and glycomic data. The performance of the model is evaluated based on
      ground-truth data, by measuring correlation of variation, RT difference across
      runs and peak-matching performance. We demonstrate that Bayesian alignment model
      improves significantly the RT alignment performance through appropriate
      integration of relevant information. AVAILABILITY AND IMPLEMENTATION: MATLAB
      code, raw and preprocessed LC-MS data are available at
      http://omics.georgetown.edu/alignLCMS.html. CONTACT: hwr@georgetown.edu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24013928
TI  - BRCA sequencing and large rearrangement testing in young Black women with breast
      cancer.
AB  - Young Black women in the United States are disproportionately afflicted with
      breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene
      mutations. In a cancer registry-based sample of young Black women with breast
      cancer, we evaluated: (1) the prevalence of BRCA mutations detected through full
      gene sequencing and large rearrangements testing and (2) proportions that
      accessed genetic services pre-dating study enrollment. Black women diagnosed with
      invasive breast cancer <=age 50 years in 2009-2012 were recruited through the
      Florida Cancer Registry. Participants completed genetic counseling, a study
      questionnaire, and consent for medical record release. Saliva specimens were
      collected for BRCA testing. Overall, 13 participants (9 %) had BRCA mutations
      detected (including 11 through full gene sequencing and two through large
      rearrangements testing). One of these large rearrangements, BRCA1 (delExon8), was
      identified in a participant who had previously tested negative on clinical
      comprehensive BRCAnalysis that was performed prior to undergoing a lumpectomy.
      Although all 144 participants met national criteria for referral for cancer
      genetic risk assessment, 61 (42 %) were referred for genetic counseling and/or
      had genetic testing preceding study enrollment, and only 20 (14 %) received
      genetic counseling. Our findings emphasize the importance of large rearrangements
      testing to increase detection of deleterious BRCA mutations in young Black women
      with breast cancer. The registry-based design of our study increase the
      generalizability of findings compared with efforts focused on clinic-based
      populations. Furthermore, results suggest efforts are needed to improve access to
      genetic counseling and testing. 

PMID- 24013929
TI  - Norvaline and norleucine may have been more abundant protein components during
      early stages of cell evolution.
AB  - The absence of the hydrophobic norvaline and norleucine in the inventory of
      protein amino acids is readdressed. The well-documented intracellular
      accumulation of these two amino acids results from the low-substrate specificity
      of the branched-chain amino acid biosynthetic enzymes that act over a number of
      related alpha-ketoacids. The lack of absolute substrate specificity of leucyl
      tRNA synthase leads to a mischarged norvalyl-tRNA(Leu) that evades the
      translational proofreading activities and produces norvaline-containing proteins,
      (cf. Apostol et al. J Biol Chem 272:28980-28988, 1997). A similar situation
      explains the presence of minute but detectable amounts of norleucine in place of
      methionine. Since with few exceptions both leucine and methionine are rarely
      found in the catalytic sites of most enzymes, their substitution by norvaline and
      norleucine, respectively, would have not been strongly hindered in small
      structurally simple catalytic polypeptides during the early stages of biological
      evolution. The report that down-shifts of free oxygen lead to high levels of
      intracellular accumulation of pyruvate and the subsequent biosynthesis of
      norvaline (Soini et al. Microb Cell Factories 7:30, 2008) demonstrates the
      biochemical and metabolic consequences of the development of a highly oxidizing
      environment. The results discussed here also suggest that a broader definition of
      biomarkers in the search for extraterrestrial life may be required.

PMID- 24013930
TI  - Conformational stabilization of the membrane embedded targeting domain of the
      lysosomal peptide transporter TAPL for solution NMR.
AB  - The ATP binding cassette transporter TAPL translocates cytosolic peptides into
      the lumen of lysosomes driven by the hydrolysis of ATP. Functionally, this
      transporter can be divided into coreTAPL, comprising the transport function, and
      an additional N-terminal transmembrane domain called TMD0, which is essential for
      lysosomal targeting and mediates the interaction with the lysosomal associated
      membrane proteins LAMP-1 and LAMP-2. To elucidate the structure of this unique
      domain, we developed protocols for the production of high quantities of cell-free
      expressed TMD0 by screening different N-terminal expression tags. Independently
      of the amino acid sequence, high expression was detected for AU-rich sequences in
      the first seven codons, decreasing the free energy of RNA secondary structure
      formation at translation initiation. Furthermore, avoiding NGG codons in the
      region of translation initiation demonstrated a positive effect on expression.
      For NMR studies, conditions were optimized for high solubilization efficiency,
      long-term stability, and high quality spectra. A most critical step was the
      careful exchange of the detergent used for solubilization by the detergent
      dihexanoylphosphatidylcholine. Several constructs of different size were tested
      in order to stabilize the fold of TMD0 as well as to reduce the conformation
      exchange. NMR spectra with sufficient resolution and homogeneity were finally
      obtained with a TMD0 derivative only modified by a C-terminal His10-tag and
      containing a codon optimized AT-rich sequence. 

PMID- 24013931
TI  - Effect of feeding inorganic chromium on growth performance, endocrine variables,
      and energy metabolites in winter-exposed buffalo calves (Bubalus bubalis).
AB  - We investigated the effect of chromium (Cr) supplementation on the growth
      performance, energy metabolites, and hormonal variation in winter-exposed buffalo
      calves. Twenty-four female buffalo calves were randomly allotted to four dietary
      treatments (n = 6) for a period of 120 days. Feeding regimen was the same in all
      the groups, except the animals in the four respective groups were additionally
      supplemented with 0.0, 0.5, 1.0, and 1.5 mg of Cr/kg DM in the form of
      CrCl3.6H2O. Calves were monitored daily for physiological variables and dry
      matter intake (DMI). Blood samples were collected at fortnightly intervals from
      each buffalo calves to measure concentrations of hormones (insulin, cortisol, and
      growth hormone), energy metabolites (glucose and non-esterified fatty acids), and
      plasma mineral levels. After 120 days of feeding trial, buffalo calves fed with
      Cr had lower (P < 0.05) circulating plasma concentrations of glucose, insulin,
      and cortisol hormones, whereas plasma thyroid hormone and non-esterified fatty
      acids concentrations were found similar (P > 0.05) among all the treatments. The
      results suggested that dietary Cr supplementation influenced plasma Cr levels
      without affecting the plasma concentrations of other trace minerals. However,
      physiological variables, nutrient intake, and growth performance of buffalo
      calves did not differ among all treatments (P > 005). In summary, the current
      study showed that supplementation of Cr at the level of 1.0 and 1.5 mg of Cr/kg
      DMI was more effective in improving glucose utilization by increasing potency of
      insulin hormone and reducing concentration of cortisol hormone. Results also
      suggested that supplemental Cr also improves blood plasma Cr levels. 

PMID- 24013932
TI  - The concentration of manganese, iron and strontium in bone of red fox Vulpes
      vulpes (L. 1758).
AB  - The aims of the study were to determine manganese (Mn), iron (Fe) and strontium
      (Sr) concentrations in fox bone samples from north-western Poland and to examine
      the relationships between the bone Mn, Fe and Sr concentrations and the sex and
      age of the foxes. In the studied samples of fox cartilage, cartilage with
      adjacent compact bone, compact bone and spongy bone, the concentrations of the
      analysed metals had the following descending order: Fe > Sr > Mn. The only
      exception was in compact bone, in which the concentrations were arranged in the
      order Sr > Fe > Mn. Manganese concentrations were significantly higher in
      cartilage, compact bone and cartilage with compact bone than in spongy bone. Iron
      concentrations were higher in cartilage and spongy bone compared with compact
      bone. Strontium concentrations were greater in compact bone than in cartilage and
      spongy bone. The manganese, iron and strontium concentrations in the same type of
      bone material in many cases correlated with each other, with the strongest
      correlation (r > 0.70) between Mn and Fe in almost all types of samples. In
      addition, concentrations of the same metals in different bone materials were
      closely correlated for Mn and Fe in cartilage and cartilage with adjacent compact
      bone, and for Sr in compact bone and cartilage with compact bone. In the fox from
      NW Poland, there were no statistically significant differences in Mn, Fe and Sr
      in any of the types of bone material between the sexes and immature and adult
      foxes. 

PMID- 24013933
TI  - Rhodium-catalyzed oxidative annulation of sulfoximines and alkynes as an approach
      to 1,2-benzothiazines.
AB  - Revitalization by oxygen: A rhodium(III)-catalyzed oxidative C?H/N?H
      activation/annulation sequence provided access to a variety of substituted 1,2
      benzothiazine derivatives from readily available NH-sulfoximines and alkynes (see
      scheme; Cp*=C5 Me5 ). The oxidation system consisted of molecular oxygen in
      combination with a catalytic amount of Fe(OAc)2 . 

PMID- 24013934
TI  - Evaluation of a matrix to calculate fungicide resistance risk.
AB  - BACKGROUND: In the European Union, assessments of resistance risk are required by
      the regulatory authorities for each fungicide product and are used to guide the
      extent of anti-resistance strategies. This paper reports an evaluation of a
      widely used 'risk matrix', to determine its predictive value. Sixty-seven unique
      cases of fungicide resistance in Europe were identified for testing the risk
      assessment scheme, where each case was the first occurrence of resistance in a
      pathogen species against a fungicide group. RESULTS: In most cases, high-,
      moderate- and low-risk categories for fungicide, pathogen and agronomic systems
      were each associated with significant differences in the number of years from
      fungicide introduction to the first detection of resistance (FDR time). The
      combined risk, calculated by multiplying the individual risk factors using the
      risk matrix, had useful predictive power (72.8% of FDR time variance accounted
      for; VAF) for all fungicides, but only limited predictive power (25.8% VAF) for
      single-site acting fungicides (the predominant type). CONCLUSION: The resistance
      risk matrix has significant, but limited, predictive value. New fungicide modes
      of action, or pathogens that have become newly prevalent, cannot be assigned to
      risk categories until new methods of resistance risk assessment are developed.

PMID- 24013935
TI  - Kinetic modeling of lipase-catalyzed esterification reaction between oleic acid
      and trimethylolpropane: a simplified model for multi-substrate multi-product ping
      pong mechanisms.
AB  - Kinetic models are among the tools that can be used for optimization of
      biocatalytic reactions as well as for facilitating process design and upscaling
      in order to improve productivity and economy of these processes. Mechanism
      pathways for multi-substrate multi-product enzyme-catalyzed reactions can become
      very complex and lead to kinetic models comprising several tens of terms. Hence
      the models comprise too many parameters, which are in general highly correlated
      and their estimations are often prone to huge errors. In this study, Novozym((r))
      435 catalyzed esterification reaction between oleic acid (OA) and
      trimethylolpropane (TMP) with continuous removal of side-product (water) was
      carried out as an example for reactions that follow multi-substrate multi-product
      ping-pong mechanisms. A kinetic model was developed based on a simplified ping
      pong mechanism proposed for the reaction. The model considered both enzymatic and
      spontaneous reactions involved and also the effect of product removal during the
      reaction. The kinetic model parameters were estimated using nonlinear curve
      fitting through unconstrained optimization methodology and the model was verified
      by using empirical data from different experiments and showed good predictability
      of the reaction under different conditions. This approach can be applied to
      similar biocatalytic processes to facilitate their optimization and design.

PMID- 24013937
TI  - Investigation of changes in psycho-physiological parameters evoked by short
      duration, intensive physical stress.
AB  - The aim of our study was to investigate changes in psycho-physiological
      parameters evoked by short duration, intensive physical stress on university
      students practicing judo at different intensities and timely manner. Stability of
      posture, muscle strength (hand force exertions), attention concentration (choice
      reaction time), cardiac parameters, (ECG, heart rate, heart rate variability),
      and oxygen saturation were measured, cardiac state and stress index were computed
      before and after the physical stress. The actual psychic state of the subjects
      was evaluated using the Spielberger's STPI-H Y-1 test which determined anxiety,
      curiosity, anger and depression level. Analysis of psychometric and physiologic
      parameters indicated significant correlations, among others, between force and
      cardiac stress (-), force and depression (-), anxiety and errors in actions (+),
      cardiac state and errors in action (-), cardiac state and depression (-). Paired
      samples tests showed the influence of intensive physical stress within groups of
      students, and independent samples tests made it possible to evaluate the power of
      medical and sport students, performing physical training at a significantly
      higher level than it is usual among the medical students. Our results proved that
      higher level physical training influences the psychic state advantageously,
      limits increases in cardiac stress level, and decreases susceptibility to anxiety
      and depression. 

PMID- 24013938
TI  - Metabolic enzyme activities and drug excretion in the small intestine and in the
      liver in the rat.
AB  - The aim of these experiments was the investigation of the correlation between the
      metabolic enzyme activities and the intestinal and hepatic excretion of p
      nitrophenol (PNP) and its metabolites (PNP-glucuronide: PNP-G and PNP-sulfate:
      PNP-S) in the same group of rats (n = 10). A jejunal loop was perfused with
      isotonic medium containing PNP in a concentration of 500 MUM. The samples were
      obtained from the luminal perfusion medium and from the bile. For enzyme assays
      tissue samples were obtained from the liver and jejunum at the end of
      experiments. Significant differences were calculated by the Student's t-test. The
      activity of UDP-glucuronyltransferase and sulfotransferase was about three times
      higher in the liver than in the small intestine. The activity of the beta
      glucuronidase was about six times higher, the activity of the arylsulfatase was
      approximately seven times greater in the liver than in the jejunum. No
      significant difference was found between the luminal appearance and the biliary
      excretion of PNP-G. Contrary to these findings, the biliary excretion of PNP-S
      was significantly higher than the luminal appearance of PNP-sulfate. It can be
      concluded that no direct correlation exists between the activity of metabolic
      enzymes and the excretion rate of PNP-metabolites in the liver and in the jejunal
      segment of the small intestine. 

PMID- 24013936
TI  - Phase I/II trial of pemetrexed plus nab-paclitaxel in advanced solid tumor
      patients with emphasis on non-small cell lung cancer.
AB  - BACKGROUND: Despite advances in targeted therapies, there is an ongoing need to
      develop new and effective cytotoxic drug combinations in non-small cell lung
      cancer (NSCLC). Based on preclinical demonstration of additive cytotoxicity, we
      evaluated the safety and efficacy of combining pemetrexed and nanoparticle
      albumin bound (nab) paclitaxel with a focus on NSCLC for phase II expansion.
      METHODS: A 3 + 3 dose-escalation design was used to determine the maximum
      tolerated dose (MTD) and the recommended phase II dose (RP2D). Three dose levels
      were tested: pemetrexed 500 mg/m(2) day 1 and nab-paclitaxel day 1 at 180, 220, &
      260 mg/m(2) every 21 days. Phase II eligibility included advanced NSCLC, <=2 line
      prior therapy, PS 0-1, adequate organ function. Primary endpoint for further
      study was response rate (RR) >= 25%. RESULTS: Planned dose escalation was
      completed without reaching the MTD. The RP2D was pemetrexed 500 mg/m(2) and nab
      paclitaxel 260 mg/m(2). The phase II portion accrued 37 pts before early closure
      due to increasing first-line pemetrexed/platinum doublet use in non-squamous
      NSCLC. In 31 assessable phase II patients there were 5 partial responses, 12
      stable disease, 14 progressive disease. The median overall survival was 8.8
      months; progressive disease 4.4 months and disease control 15.6 months.
      CONCLUSIONS: Pemetrexed 500 mg/m(2) day 1 with nab-paclitaxel 260 mg/m(2) was
      feasible and well tolerated. The phase II component demonstrated activity in
      second/third-line therapy of advanced NSCLC; response rate 14% and disease
      control rate 46%. Treatment practice patterns of advanced NSCLC have evolved;
      further trials of this regimen are not planned.

PMID- 24013939
TI  - Short and long latency response due to transition from bilateral to unilateral
      contraction.
AB  - The aim of this study was to investigate the effect of fast and slow relaxation
      of the knee extensor muscle of the dominant leg on torque-time curve of the
      unilaterally contracting contralateral muscle. Eight adult male subjects were
      recruited without bilateral deficit. In Task 1 subjects exerted bilateral and
      unilateral torque and bilateral index was calculated. In Task 2 subjects relaxed
      the right knee extensors as slow as possible while maximum activation of the
      contralateral muscle had to be maintained. In Task 3 the relaxation was as fast
      as possible. During slow relaxation the short latency response (dM1) was 6.6%
      torque reduction in the left leg. On the contrary fast muscle relaxation resulted
      in a 7.3% increase. During long latency response the torque increased in both
      tasks, but did not exceed the torque measured in Task 1. Significant correlation
      was found between the rate of torque reduction (RTR) and dM1 (r = 0.95, P <
      0.001), time to peak (t1) and dM1 (r = 0.812, P < 0.01). The regression analysis
      indicated that RTR greater or less than -1.0 Nm/ms results in opposite short
      latency response. We concluded that the different tasks for two knee extensor
      muscles result in transient interhemispheric effects which are time and rate of
      torque reduction dependent. 

PMID- 24013940
TI  - Changes in metabolic and muscle damage indicators following a single bout of jump
      training on stair versus at level.
AB  - We hypothesized that stair-jump exercise would induce less muscle damage and
      greater acute metabolic responses than level-jumps. METHODS: Trained males
      executed 100 unilateral jumps on stairs with one leg, and at level with the other
      leg, with two weeks hiatus. Maximal isometric voluntary torque (MVC) and rate of
      torque development (RTD)in the quadriceps, and unilateral vertical jump height
      (VJ) were determined in the trained leg at pre-exercise,immediately at post-
      (IP), 24 h and 48 h after exercise. Serum creatine kinase (CK) level and delayed
      onset muscle soreness (DOMS) were evaluated at pre-exercise, 24 h and 48 h. Acute
      lactate and heart rate responses were also measured. RESULTS: Lactate and heart
      rate at IP increased similarly under the two conditions. CK was elevated and MVC
      was depressed while RTD and VJ remained unchanged at 24 h in both types of
      training. MVC recovered at 48 h only after stair-jump exercise. DOMS developed
      only after level-jumps. Except DOMS, no effects of condition were found in any
      other variables. CONCLUSIONS: We conclude that vigorous stair-jump exercise
      highly stresses the aerobic and the anaerobic energy system, and it preserves
      power and rapid torque generating ability 24 h after exercise. Stair-jump could
      be one alternative exercise to prevent muscle soreness.

PMID- 24013941
TI  - Changes in muscle architecture induced by low load blood flow restricted
      training.
AB  - In order to ascertain whether differing structural mechanisms could underlie
      blood flow restricted training (BFRT) and high intensity training (HIT), this
      study had two aims: (i) to gain an insight into the acute variations of muscle
      architecture following a single bout of two different volumes of BFRT, and (ii)
      to compare these variations with those observed after HIT. Thirty-five young men
      volunteered for the study and were randomly divided into three groups: BFRT low
      volume (BFRT LV), BFRT high volume (BFRT HV) and traditional high intensity
      resistance training (HIT). All subjects performed a bilateral leg extension
      exercise session with a load of 20% of one repetition maximum (1RM) in the BFRT
      groups, whereas the load of the HIT group was equivalent to an 85% of their 1RM.
      Before and immediately after the exercise bout, ultrasound images were taken from
      the rectus femoris (RF) and the vastus lateralis (VL). All groups increased their
      RF (p < 0.001) and VL (p < 0.001) muscle thickness, while the increases in
      pennation angle were larger in HIT as compared to BFRT LV (p = 0.013) and BFRT HV
      (p = 0.037). These results support the hypothesis that acute muscle cell swelling
      may be involved in the processes underlying BFRT induced muscle hypertrophy.
      Furthermore, our data indicate differing structural responses to exercise between
      BFRT and HIT. 

PMID- 24013942
TI  - Relationship between exhaled nitric oxide and the frequency of severe acute
      exacerbation of COPD: 3-year follow-up.
AB  - In a recent trial we have assessed fractional exhaled nitric oxide (FENO) in a
      cohort of patients with an acute exacerbation of chronic obstructive pulmonary
      disease (COPD). In the current study we have retrospectively investigated the
      frequency of severe hospitalization-associated exacerbations in the same cohort
      over 3 years after the initial FENO measurement. A total of 58 COPD patients were
      enrolled and allocated either into the low (< 27 ppb) or the high (>= 27 ppb)
      FENO group depending on their FENO level at exacerbation. Beside the annual rate
      of exacerbations, sputum culture results and the frequency of antibiotic
      treatments were also analyzed during the follow-up. Both the number of
      exacerbations per patient-year and the hospitalization days due to exacerbations
      were significantly increased in patients from the low FENO group compared to
      those from the high FENO group. Sputum samples derived from patients in the low
      FENO group were more frequently indicative of a bacterial infection compared to
      those obtained from the other subgroup. Also, the frequency of antibiotic
      treatments was significantly increased in subjects from the low FENO group.
      Results of this pilot study suggest that COPD patients have diverse risks for
      future exacerbations depending on their FENO levels at exacerbation. 

PMID- 24013943
TI  - Effects of maximum intensity aerobic swimming exercise until exhaustion at
      different times of day on the hematological parameters in rats.
AB  - The aims of this study were: a) to analyze the time of day effect on the aerobic
      capacity and time to exhaustion at aerobic capacity intensity (TE), and b) to
      analyze the physiological impact of handling and exercise testing during the
      light and dark periods, based on hematological parameters. Eighty rats were
      randomly divided into two control groups (C12 and C20) and two exercise groups
      (E12 and E20), assessed at 12:00 h (C12 and E12) or 20:00 h (C20 and E20). The
      lactate minimum intensity (LMi) was measured and after 48 h the exercise groups
      were subjected to a bout of swimming until exhaustion at LMi (TE). The TE was
      1.30 +/- 0.51 h for the E12 group and 1.81 +/- 0.77 h for the E20 group (p =
      0.03). The time of day effect was significant for all white blood cell counts
      (12:00 h > 20:00 h). Chronic handling and performing exercise tests at 12:00 h
      (light period) resulted in an increased WBC counts and decreased exercise
      tolerance. The favorable time of day for aerobic capacity and performance
      assessment and hematological parameters was at 20:00 h (dark period), which is
      associated with the wakefulness period of the assessed animals. 

PMID- 24013945
TI  - Anti-inflammatory M2, but not pro-inflammatory M1 macrophages promote
      angiogenesis in vivo.
AB  - OBJECTIVE: Macrophages show extreme heterogeneity and different subsets have been
      characterized by their activation route and their function. For instance,
      macrophage subsets are distinct by acting differently under pathophysiological
      conditions such as inflammation and cancer. Macrophages also contribute to
      angiogenesis, but the role of various specific subsets in angiogenesis has not
      been thoroughly investigated. METHODS AND RESULTS: Matrigel supplemented with
      macrophage subsets [induced by IFNgamma (M1), IL-4 (M2a) or IL-10 (M2c)] was
      injected subcutaneously in C57BL/6 J mice and analyzed by CD31 staining after 14
      days. Increased numbers of endothelial cells and tubular structures were observed
      in M2-enriched plugs compared to control and other subsets. Additionally, more
      tubular structures formed in vitro in the presence of M2 macrophages or their
      conditioned medium. To identify a mechanism for the pro-angiogenic effect, gene
      expression of angiogenic growth factors was analyzed. Induced expression of basic
      fibroblast growth factor (Fgf2), insulin-like growth factor-1 (Igf1), chemokine
      (C-C motif) ligand 2 (Ccl2) and placental growth factor (Pgf) was observed in M2
      macrophages. Using a blocking antibody of PlGF to inhibit M2c induced
      angiogenesis resulted in mildly reduced (40 %) tube formation whereas
      neutralization of FGF-2 (M2a) signaling by sFGFR1-IIIc affected tube formation by
      nearly 75 %. CONCLUSIONS: These results indicate that macrophages polarized
      towards an M2 phenotype have a higher angiogenic potential compared to other
      subsets. Furthermore, we propose FGF signaling for M2a- and PlGF signaling for
      M2c-induced angiogenesis as possible working mechanisms, yet, further research
      should elucidate the exact mechanism for M2-induced angiogenesis.

PMID- 24013944
TI  - Molecular basis for downregulation of C5a-mediated inflammation by IgG1 immune
      complexes in allergy and asthma.
AB  - Allergy and asthma are triggered primarily by the binding of allergen-specific
      immunoglobulin E (IgE)-allergen complexes to their receptors, recognition of the
      allergens by antigen-presenting cells, and allergen presentation to the T cells.
      These events lead to mucus secretions, runny nose, itchy eyes, sneezing, airway
      hyperresponsiveness, and nasal congestion. Complement 5a (C5a) has emerged as a
      central molecule that mediates these allergic reactions. Many allergens and
      allergen-specific IgG immune complexes (IgG-ICs) cause complement activation and
      C5a generation. C5a interaction with its receptor (C5aR) leads to the
      infiltration and activation of several immunologic cell types and the secretion
      of pathogenic inflammatory and proinflammatory mediators. However, IgG1-IC
      binding to the IgG inhibitory Fc gamma receptor (FcgammaRIIB) suppresses C5aR
      mediated inflammatory signaling and, hence, may reduce the inflammatory immune
      responses through this FcgammaRIIB-mediated pathway. Reviews of the IgG1-IC
      interactions with C5a-mediated inflammatory immune responses suggest that IgG1-IC
      C5a inhibitory therapy may reduce inflammation in allergic diseases. 

PMID- 24013946
TI  - Resistance exercise training does not affect plasma irisin levels of hemodialysis
      patients.
AB  - Irisin, a hormone secreted by myocytes induced in exercise, acts as a muscle
      derived energy-expenditure signal that binds to undetermined receptors on the
      white adipose tissue surface, stimulating its browning and uncoupling protein 1
      (UCP1) expression. The purpose of this study was to assess the effect of an
      intradialytic resistance exercise training program (RETP) on plasma irisin levels
      of hemodialysis (HD) patients and compare the baseline plasma irisin levels of HD
      patients to healthy subjects. This longitudinal study enrolled 26 patients
      undergoing HD (50% men, 44.8+/-14.1 years, body mass index (BMI) 23.5+/-3.9
      kg/m2). The healthy subjects group consisted of 11 women and 7 men with mean age
      of 50.9+/-6.6 years and BMI, 24.2+/-2.7 kg/m2. Anthropometric and biochemistry
      parameters (Irisin by Enzyme-Linked Immunosorbent Assay) were measured at the
      baseline and after 6 months of RETP (in both lower limbs). There was no
      difference regarding gender, age, and BMI between HD patients and healthy
      subjects. Plasma irisin levels in HD patients were lower than in healthy subjects
      (71.0+/-41.6 vs. 101.3+/-12.5 ng/ml, p<0.05). Although the muscle mass increased
      in consequence of exercise [evaluated by arm muscle area from 27.9 (24.1) to 33.1
      (19.0) cm2], plasma irisin did not differ significantly after exercises (71.0+/
      41.6 vs. 73.3+/-36.0 ng/ml). HD patients seem to have lower plasma irisin when
      compared to healthy subjects. Moreover, a resistance exercise training program
      was unable to augment plasma irisin despite increasing muscle mass.

PMID- 24013947
TI  - GH responsiveness before and after a 3-week multidisciplinary body weight
      reduction program associated with an incremental respiratory muscle endurance
      training in obese adolescents.
AB  - Several studies have demonstrated that the obesity-related hyposomatropism is
      usually reversible after a consistent weight loss induced by diet and/or
      bariatric surgery. Recently, a single bout of respiratory muscle endurance
      training (RMET) by means of a specific commercially available device (Spiro
      Tiger(r)) has been reported to induce a marked GH response in obese adults, its
      GH-releasing effect being significantly lower in obese adolescents. The GH
      response disappeared in both obese adults and adolescents when RMET was repeated
      at 2-h intervals in-between. The aim of the present study was to evaluate GH
      responses to repeated bouts of RMET administered before and after a 3-week in
      hospital multidisciplinary body weight reduction program (entailing energy
      restricted diet, 90 min/daily aerobic physical activity, psychological
      counseling, and nutritional education) combined with a progressively increasing
      RMET (15 daily sessions, 5 sessions per week) in 7 obese male adolescents [age:
      12-17 years; body mass index (BMI): 38.5+/-3.1 kg/m2; percent fat mass (FM):
      37.0+/-2.0%]. Blood samplings for GH determinations were collected during the 1st
      and 15th sessions, which were composed of 2 consecutive bouts of RMET (of
      identical intensity and duration) at 2-h interval in-between. At the beginning of
      the study, baseline GH levels significantly increased after the first bout of
      RMET in all subjects (p<0.05). The administration of the second bout of RMET
      resulted in a significantly lower (p<0.05) GH increase in comparison with the
      first one. Three weeks of the integrated intervention significantly reduced both
      body weight (from 115.3+/-9.2 kg to 111.5+/-8.7 kg, p<0.05) and FM (from 43.1+/
      5.7 kg to 41.9+/-5.3 kg, p<0.05), these combined effects being, however, not
      sufficient to influence GH responsiveness to the 2 repeated bouts of RMET (GH
      peaks to the first bout: 4.8+/-1.6 ng/ml vs. 4.8+/-1.6 ng/ml; GH peaks to the
      second bout: 0.9+/-0.2 ng/ml vs. 1.1+/-0.1 ng/ml, before and after 3 weeks of the
      treatment, respectively, p=NS). In conclusion, a 3-week incremental RMET combined
      with a body weight reduction intervention does not seem useful to positively
      influence the reduced GH responsiveness to 2 repeated RMET bouts in obese
      adolescents. More intensive and/or long-term RMET protocols, associated with
      energy-restricted diets, determining more consistent changes in body composition,
      are likely needed to restore the impaired GH-IGF-1 function of obese adolescents.

PMID- 24013949
TI  - The -842G/C polymorphisms of PIN1 contributes to cancer risk: a meta-analysis of
      10 case-control studies.
AB  - BACKGROUND: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) plays
      an important role in cancer development. The relationship between PIN1 -842G/C
      (rs2233678) polymorphism and cancer risk was inconclusive according to published
      literature. METHODOLOGY/PRINCIPAL FINDINGS: A literature search, up to February
      2013, was carried out using PubMed, EMBASE and the China National Knowledge
      Infrastructure (CNKI) database. A total of 10 case-control studies including 4619
      cases and 4661 controls contributed to the quantitative analysis. Odds ratio (OR)
      and 95% confidence intervals (95% CI) were used to assess the strength of
      association. Overall, individuals with the variant CG (OR = 0.728, 95% CI:
      0.585,0.906; Pheterogeneity<0.01) and CG/CC (OR = 0.731, 95% CI: 0.602,0.888;
      Pheterogeneity<0.01) genotypes were associated with a significantly reduced
      cancer risk compared with those with wild GG genotype. Sub-group analysis
      revealed that the variant CG (OR = 0.635, 95% CI: 0.548,0.735; Pheterogeneity =
      0.240) and CG/CC (OR = 0.645, 95% CI: 0.559,0.744, Pheterogeneity = 0.258)
      genotypes still showed an reduced risk of cancer in Asians; while no significant
      association was observed in Caucasians (CG vs.GG: OR = 0.926, 95% CI:
      0.572,1.499, Pheterogeneity<0.01; CG/CC vs. GG: OR = 0.892, 95% CI: 0.589,1.353;
      Pheterogeneity<0.01). Furthermore, sensitivity analysis confirmed the stability
      of results. Begg's funnel plot and Egger's test did not reveal any publication
      bias. CONCLUSIONS: This meta-analysis suggests that the PIN1 -842G/C polymorphism
      is associated with a significantly reduced risk of cancer, especially in Asian
      populations.

PMID- 24013950
TI  - Mechanism of action of sodium channel blocker insecticides (SCBIs) on insect
      sodium channels.
AB  - Sodium channel blocker insecticides (SCBIs) are a relatively new class of
      insecticides, with a mechanism of action different from those of other classes of
      insecticides that target voltage-gated sodium channels. These compounds have no
      effect at hyperpolarized membrane potentials, but cause a voltage-dependent,
      nearly irreversible block as the membrane potential is depolarized. The mechanism
      of action of SCBIs is similar to that of local anesthetics (LAs), class I
      anticonvulsants and class I antiarrhythmics. In this article, we review the
      physiological actions of these compounds on the whole animal, the nervous system
      and sodium channels, and also present the results from recent studies that
      elucidate the receptor site of SCBIs.

PMID- 24013948
TI  - A review of feature reduction techniques in neuroimaging.
AB  - Machine learning techniques are increasingly being used in making relevant
      predictions and inferences on individual subjects neuroimaging scan data.
      Previous studies have mostly focused on categorical discrimination of patients
      and matched healthy controls and more recently, on prediction of individual
      continuous variables such as clinical scores or age. However, these studies are
      greatly hampered by the large number of predictor variables (voxels) and low
      observations (subjects) also known as the curse-of-dimensionality or small-n
      large-p problem. As a result, feature reduction techniques such as feature subset
      selection and dimensionality reduction are used to remove redundant predictor
      variables and experimental noise, a process which mitigates the curse-of
      dimensionality and small-n-large-p effects. Feature reduction is an essential
      step before training a machine learning model to avoid overfitting and therefore
      improving model prediction accuracy and generalization ability. In this review,
      we discuss feature reduction techniques used with machine learning in
      neuroimaging studies. 

PMID- 24013951
TI  - Effect of catenation and basicity of pillared ligands on the water stability of
      MOFs.
AB  - Metal-organic frameworks (MOFs) have extremely high surface areas and pore
      volumes, tunable pore sizes and chemical functionalities and are an interesting
      addition to the field of porous materials. One of the key challenges that needs
      to be overcome to elevate MOFs to the applied level is their sensitivity to humid
      environments. The work reported here seeks to address this critical issue by
      examining two important contributors to MOF stability or instability: basicity
      (pKa value) of the pillar ligand and catenation of the framework. Catenation is
      the interpenetration or interweaving of two or more identical and independent
      frameworks. We demonstrate that, using catenation in combination with a pillaring
      strategy, it is possible to obtain water stable MOFs even when the pillar ligand
      has lower basicity (pKa value). This study shows that after 90% relative humidity
      (RH) exposure, comparing Zn-BDC-DABCO (DMOF) and Zn-BDC-BPY (MOF-508), MOF-508 is
      stable due to its two-fold interpenetration that prevents significant water
      adsorption. In contrast, comparing non-catenated isostructural pillared MOFs Zn
      TMBDC-DABCO (DMOF-TM) and Zn-TMBDC-BPY (MOF-508-TM), MOF-508-TM is unstable since
      BPY is less basic (higher pKa) and less rigid than DABCO. 

PMID- 24013952
TI  - ORIUM: optimized RDC-based Iterative and Unified Model-free analysis.
AB  - Residual dipolar couplings (RDCs) are NMR parameters that provide both structural
      and dynamic information concerning inter-nuclear vectors, such as N-H(N) and
      Calpha-Halpha bonds within the protein backbone. Two approaches for extracting
      this information from RDCs are the model free analysis (MFA) (Meiler et al. in J
      Am Chem Soc 123:6098-6107, 2001; Peti et al. in J Am Chem Soc 124:5822-5833,
      2002) and the direct interpretation of dipolar couplings (DIDCs) (Tolman in J Am
      Chem Soc 124:12020-12030, 2002). Both methods have been incorporated into
      iterative schemes, namely the self-consistent RDC based MFA (SCRM) (Lakomek et
      al. in J Biomol NMR 41:139-155, 2008) and iterative DIDC (Yao et al. in J Phys
      Chem B 112:6045-6056, 2008), with the goal of removing the influence of
      structural noise in the MFA and DIDC formulations. Here, we report a new
      iterative procedure entitled Optimized RDC-based Iterative and Unified Model-free
      analysis (ORIUM). ORIUM unifies theoretical concepts developed in the MFA, SCRM,
      and DIDC methods to construct a computationally less demanding approach to
      determine these structural and dynamic parameters. In all schemes, dynamic
      averaging reduces the actual magnitude of the alignment tensors complicating the
      determination of the absolute values for the generalized order parameters. To
      readdress this scaling issue that has been previously investigated (Lakomek et
      al. in J Biomol NMR 41:139-155, 2008; Salmon et al. in Angew Chem Int Edit
      48:4154-4157, 2009), a new method is presented using only RDC data to establish a
      lower bound on protein motion, bypassing the requirement of Lipari-Szabo order
      parameters. ORIUM and the new scaling procedure are applied to the proteins
      ubiquitin and the third immunoglobulin domain of protein G (GB3). Our results
      indicate good agreement with the SCRM and iterative DIDC approaches and signify
      the general applicability of ORIUM and the proposed scaling for the extraction of
      inter-nuclear vector structural and dynamic content. 

PMID- 24013953
TI  - An updated review of sepsis for the anesthesiologist.
AB  - Severe sepsis and septic shock continue to be among of the leading causes of
      death in intensive care unit patients, carrying an estimated mortality rate
      between 30% and 50%. This article provides an evidence-based focused review of
      sepsis, including an update on management strategies based on the most recent
      guidelines published by the Surviving Sepsis Campaign. 

PMID- 24013954
TI  - Atmospheric pressure room temperature plasma jets facilitate oxidative and
      nitrative stress and lead to endoplasmic reticulum stress dependent apoptosis in
      HepG2 cells.
AB  - Atmospheric pressure room temperature plasma jets (APRTP-Js) that can emit a
      mixture of different active species have recently found entry in various medical
      applications. Apoptosis is a key event in APRTP-Js-induced cellular toxicity, but
      the exact biological mechanisms underlying remain elusive. Here, we explored the
      role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in
      APRTP-Js-induced apoptosis using in vitro model of HepG2 cells. We found that
      APRTP-Js facilitated the accumulation of ROS and RNS in cells, which resulted in
      the compromised cellular antioxidant defense system, as evidenced by the
      inactivation of cellular antioxidants including glutathione (GSH), superoxide
      dismutase (SOD) and catalase. Nitrotyrosine and protein carbonyl content analysis
      indicated that APRTP-Js treatment caused nitrative and oxidative injury of cells.
      Meanwhile, intracellular calcium homeostasis was disturbed along with the
      alteration in the expressions of GRP78, CHOP and pro-caspase12. These effects
      accumulated and eventually culminated into the cellular dysfunction and
      endoplasmic reticulum stress (ER stress)-mediated apoptosis. The apoptosis could
      be markedly attenuated by N-acetylcysteine (NAC, a free radical scavenger), which
      confirmed the involvement of oxidative and nitrative stress in the process
      leading to HepG2 cell apoptosis by APRTP-Js treatment. 

PMID- 24013955
TI  - Investigating the candidacy of LPS-based glycoconjugates to prevent invasive
      meningococcal disease: conjugates based on core oligosaccharides.
AB  - In this study we have prepared glycoconjugates with core oligosaccharides (OS)
      from the lipopolysaccharide (LPS) of Neisseria meningitidis, thus avoiding the
      neo-epitopes of the deacylated lipid A region of the derived LPS molecule
      identified in our previous studies. A comprehensive investigation was performed
      with glycoconjugates prepared from the most extended to the most truncated core
      OS still maintaining the conserved inner core epitope. As previously, we have
      established reproducible bactericidal killing of the homologous antigen
      elaborating strain, but a failure to kill wild-type strains. In these studies it
      was evident that the linker molecules used in the conjugation methodologies were
      dominating the immune response. However, when galE core OS based conjugates were
      prepared without utilizing linkers, via direct reductive amination, we failed to
      generate an immune response to even the homologous antigen. We also identified
      that immunisation with the galE antigen via linker methodologies provoked an
      immune response that was dependent upon key residues of the conserved inner core
      OS structure, whereas the immune responses to lgtB and lgtA antigens did not
      involve the inner core OS. This comprehensive study has, despite our best
      efforts, cast significant doubt as to the utility of the conserved inner core
      region of the meningococcal LPS as a potential vaccine antigen. 

PMID- 24013956
TI  - Mutation in the C-di-AMP cyclase dacA affects fitness and resistance of
      methicillin resistant Staphylococcus aureus.
AB  - Faster growing and more virulent strains of methicillin resistant Staphylococcus
      aureus (MRSA) are increasingly displacing highly resistant MRSA. Elevated fitness
      in these MRSA is often accompanied by decreased and heterogeneous levels of
      methicillin resistance; however, the mechanisms for this phenomenon are not yet
      fully understood. Whole genome sequencing was used to investigate the genetic
      basis of this apparent correlation, in an isogenic MRSA strain pair that differed
      in methicillin resistance levels and fitness, with respect to growth rate.
      Sequencing revealed only one single nucleotide polymorphism (SNP) in the
      diadenylate cyclase gene dacA in the faster growing but less resistant strain.
      Diadenylate cyclases were recently discovered to synthesize the new second
      messenger cyclic diadenosine monophosphate (c-di-AMP). Introduction of this
      mutation into the highly resistant but slower growing strain reduced resistance
      and increased its growth rate, suggesting a direct connection between the dacA
      mutation and the phenotypic differences of these strains. Quantification of
      cellular c-di-AMP revealed that the dacA mutation decreased c-di-AMP levels
      resulting in reduced autolysis, increased salt tolerance and a reduction in the
      basal expression of the cell wall stress stimulon. These results indicate that c
      di-AMP affects cell envelope-related signalling in S. aureus. The influence of c
      di-AMP on growth rate and methicillin resistance in MRSA indicate that altering c
      di-AMP levels could be a mechanism by which MRSA strains can increase their
      fitness levels by reducing their methicillin resistance levels. 

PMID- 24013958
TI  - Addition by Subtraction: The Relation Between Dropout Rates and School-Level
      Academic Achievement.
AB  - BACKGROUND/CONTEXT: Efforts to improve student achievement should increase
      graduation rates. However, work investigating the effects of student-level
      accountability has consistently demonstrated that increases in the standards for
      high school graduation are correlated with increases in dropout rates. The most
      favored explanation for this finding is that high-stakes testing policies that
      mandate grade repetition and high school exit exams may be the tipping point for
      students who are already struggling academically. These extra demands may, in
      fact, push students out of school. PURPOSE/OBJECTIVE/FOCUS: This article examines
      two hypotheses regarding the relation between school-level accountability and
      dropout rates. The first posits that improvements in school performance lead to
      improved success for everyone. If school-level accountability systems improve a
      school for all students, then the proportion of students performing at grade
      level increases, and the dropout rate decreases. The second hypothesis posits
      that schools facing pressure to improve their overall accountability score may
      pursue this increase at the cost of other student outcomes, including dropout
      rate. RESEARCH DESIGN: Our approach focuses on the dynamic relation between
      school-level academic achievement and dropout rates over time-that is, between
      one year's achievement and the subsequent year's dropout rate, and vice versa.
      This article employs longitudinal data of records on all students in North
      Carolina public schools over an 8-year period. Analyses employ fixed-effects
      models clustering schools and districts within years and controls each year for
      school size, percentage of students who were free/reduced-price lunch eligible,
      percentage of students who are ethnic minorities, and locale. FINDINGS/RESULTS:
      This study finds partial evidence that improvements in school-level academic
      performance will lead to improvements (i.e., decreases) in school-level dropout
      rates. Schools with improved performance saw decreased dropout rates following
      these successes. However, we find more evidence of a negative side of the quest
      for improved academic performance. When dropout rates increase, the performance
      composites in subsequent years increase. CONCLUSIONS/RECOMMENDATIONS:
      Accountability systems need to remove any indirect benefit a school may receive
      from increasing its dropout rate. Schools should be held accountable for those
      who drop out of school. Given the personal and social costs of dropping out,
      accountability systems need to place more emphasis on dropout prevention. Such an
      emphasis could encompass increasing the dropout age and having the school's
      performance composite include scores of zero on end-of-grade tests for those who
      leave school.

PMID- 24013957
TI  - Alcohol brief intervention in community pharmacies: a feasibility study of
      outcomes and customer experiences.
AB  - BACKGROUND: Studies indicate that community pharmacy-based alcohol brief
      intervention (BI) is feasible. However, few studies report significant reductions
      in post-BI alcohol consumption and customer experience. Cost-effectiveness has
      not been previously examined. OBJECTIVES: This 5 month study adopted a single
      group pre- and post-experimental design to: (1) assess uptake of the community
      pharmacy alcohol BI service; (2) establish post-BI changes in alcohol consumption
      for hazardous drinkers; (3) report the acceptability of the service to customers
      who received it; and (4) undertake a preliminary economic evaluation of the
      service through establishing whether pharmacy-based alcohol BI affected health
      and social care costs, including lost employment costs, and whether it was cost
      effective. SETTING: 26 community pharmacies in south London, UK. METHOD: Trained
      pharmacists used the AUDIT-C and a retrospective 7-day Drinking Diary to identify
      risky drinkers and inform feedback and advice. Harmful drinkers were referred to
      their general practitioner and/or specialist alcohol services. A confidential
      service feedback questionnaire was completed by alcohol BI recipients. Baseline
      and 3-month follow-up telephone interviews were conducted with hazardous and low
      risk drinkers to assess post-BI alcohol use change and service cost
      effectiveness. MAIN OUTCOME MEASURES: AUDIT-C, 7-day alcohol unit consumption,
      drinking days, cost utilisation data. RESULTS: Of the 663 eligible customers
      offered alcohol BI, 141 (21 %) took up the service. Three-quarters of customers
      were identified as risky drinkers. Follow-up interviews were conducted with 61
      hazardous/low risk drinkers (response rate = 58 %). Hazardous drinkers were found
      to significantly reduce their 7-day alcohol unit consumption and drinking days,
      but not AUDIT-C scores. The majority of harmful drinkers (91 %, n = 10) who were
      contactable post-BI had accessed further alcohol related services. Customer
      feedback was generally positive. Over 75 % of customers would recommend the
      service to others. The cost of delivering the service was estimated to be L 134.
      The difference in service costs pre-BI and post-BI was not statistically
      significant and remained non-significant when calculated on 500 customers
      receiving the intervention. CONCLUSION: Community pharmacy-based alcohol BI is a
      low cost service that may not have immediate beneficial impact on health and
      social service use, but can be effective in reducing drinking in hazardous
      drinkers.

PMID- 24013959
TI  - Dry eye disease, dry eye symptoms and depression: the Beijing Eye Study.
AB  - AIM: To investigate the association between dry eye symptoms and depression in an
      adult population. METHODS: In this population-based cross-sectional study, a
      random sample of 1957 subjects from the Beijing Eye Study was examined for dry
      eye disease (DED) in 2006. All patients completed an interviewer-assisted
      questionnaire on dry eye symptoms and underwent measurement of tear break-up time
      (TBUT), slit-lamp evaluation of corneal staining and meibomian gland dysfunction
      (MGD), and the Schirmer test. In 2011, 1456 subjects from this sample were
      evaluated for depression using a depression scale. The association between
      depression symptoms and dry eye clinical tests was evaluated. RESULTS: Definite
      depression was more prevalent in patients with DED than in subjects without DED
      (13.7+/-0.4% vs 8.6+/-0.3%, p=0.02). The depression score was correlated with dry
      eye symptoms (correlation coefficient r=0.07; p=0.013) but not with TBUT
      (p=0.18), the Schirmer test (p=0.37), corneal staining (p=0.30) and MGD
      evaluation (p=0.93). In multivariate regression analysis, the risk of definite
      depression remained significantly associated with dry eye symptoms (p=0.028)
      after adjusting for lower cognitive status (p=0.01), rural region of habitation
      (p=0.023) and lower body weight (p=0.05). CONCLUSIONS: In an older population
      from Beijing, depression was associated with DED and in particular with dry eye
      symptoms.

PMID- 24013961
TI  - Human leukemic cell lines synthesize hyaluronan to avoid senescence and resist
      chemotherapy.
AB  - Hyaluronan (HA) is one of the major components of the extracellular matrix.
      Several solid tumors produce high levels of HA, which promotes survival and
      multidrug resistance (MDR). HA oligomers (oHAs) can block HA effects. However,
      little is known about the role of HA in hematological malignancies. The aim of
      this work was to determine whether HA or its oligomers can modulate the
      proliferation of leukemia cells as well as their effect on MDR. Receptors and
      signaling pathways involved were also analyzed. For this purpose, the human
      leukemic cell lines K562 and Kv562, which are sensitive and resistant to
      Vincristine (VCR), respectively, were used. We demonstrated that HA induced cell
      proliferation in both cell lines. On K562 cells, this effect was mediated by
      cluster differentiation 44 (CD44) and activation of both phosphoinositide 3
      kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase kinase
      (MEK)/extracellular signal-regulated kinase (ERK) pathways, whereas on Kv562
      cells, the effect was mediated by receptor for hyaluronan-mediated motility
      (RHAMM) and PI3K/Akt activation. The inhibition of HA synthesis by 4
      methylumbelliferone (4MU) decreased cell line proliferation and sensitized Kv562
      to the effect of VCR through P-glycoprotein (Pgp) inhibition, in both cases with
      senescence induction. Moreover, oHAs inhibited K562 proliferation mediated by
      CD44 as well as Akt and ERK down-regulation. Furthermore, oHAs sensitized Kv562
      cells to VCR by Pgp inhibition inducing senescence. We postulate that the
      synthesis of HA would promote leukemia progression mediated by the triggering of
      the above-mentioned proliferative signals. These findings highlight the potential
      use of oHAs and 4MU as coadjuvant for drug-resistant leukemia. 

PMID- 24013960
TI  - Utilization of major fucosylated and sialylated human milk oligosaccharides by
      isolated human gut microbes.
AB  - Human milk oligosaccharides (HMOS) are not digested in the proximal intestine. In
      distal intestine, HMOS collectively modify the microbiota, but the response of
      individual bacteria to individual components of the HMOS is not well defined.
      Here, each of 25 major isolates of the human intestinal microbiota was fed
      individual major fucosylated and sialylated HMOS in anaerobic culture. This
      allowed for an assessment of the influence of specific HMOS on the growth and
      metabolic products of individual microbiota bacteria. Most Bifidobacteria spp.
      and Bacteroides spp. grew, induced alpha-L-fucosidase activity, and produced
      abundant lactate or short-chain fatty acids (SCFAs) when fed 2'-fucosyllactose
      (2'-FL), 3-FL, and lactodifucotetraose (LDFT). Lactobacillus delbrueckii
      ATCC7830, Enterococcus faecalis ATCC19433, and Streptococcus thermophilus
      ATCC19258 exhibited slight growth, pH reduction, and lactate production when
      supplemented with 2'-FL or 3-FL, but not LDFT. Supplementation with 3'
      sialyllactose (3'-SL) and 6'-SL promoted moderate growth of Bifidobacterium
      longum JCM7007, 7009, 7010, 7011, 1272, 11347, ATCC15708, Bacteroides vulgatus
      ATCC8482, and B. thetaiotaomicron ATCC29148; accordingly, these bacteria
      exhibited greater neuraminidase activity and produced copious lactate, SCFA, or
      both. Lactobacillus delbrueckii ATCC7830 also consumed 6'-SL. In contrast,
      Clostridium spp., L. rhamnosus ATCC53103, E. faecalis ATCC29200, Staphylococcus
      spp., Enterobacter spp., and Escherichia coli K12 did not consume milk
      oligosaccharides nor produce appreciable acidic fermentation products. Specific
      Bifidobacteria and Bacteroides differentially digest specific individual HMOS,
      with the major fucosylated milk oligosaccharides most strongly stimulating key
      species of mutualist symbionts. This suggests strategies for treating dysbiosis
      of the microbiota and associated inflammatory disorders.

PMID- 24013962
TI  - Psychological care in a national health service: challenges for people with
      diabetes.
AB  - Recently, there has been a growing interest in psychological problems in people
      with diabetes and a concomitant increasing concern that these often go unreported
      and, thus, unidentified and treated. This has serious implications for both the
      self-management of diabetes and the individual's quality of life. In this review
      article we consider the question of screening for depression in people with
      diabetes within a national health service in the UK. The inadequacies of
      psychological care for patients with diabetes are discussed, in particular with
      regard to the importance of distinguishing between depressive symptoms and
      emotional distress related to having diabetes. Criteria for assessing the
      validity of screening for depression are discussed, together with national and
      international recommendations, with particular emphasis on current practice. The
      screening strategy currently recommended for implementation in primary care in
      the UK is outlined. The need for rigorous evaluation of screening initiatives is
      highlighted and a key conclusion is that case-finding alone is unlikely to be
      effective in terms of improving patient outcomes unless considered and applied in
      the context of overall case management. This review highlights the barriers and
      challenges to optimizing care for patients with co-morbid diabetes and
      depression, and outlines the therapies currently available in the UK, which might
      be disseminated in other countries. 

PMID- 24013964
TI  - Early and middle holocene hunter-gatherer occupations in western Amazonia: the
      hidden shell middens.
AB  - We report on previously unknown early archaeological sites in the Bolivian
      lowlands, demonstrating for the first time early and middle Holocene human
      presence in western Amazonia. Multidisciplinary research in forest islands
      situated in seasonally-inundated savannahs has revealed stratified shell middens
      produced by human foragers as early as 10,000 years ago, making them the oldest
      archaeological sites in the region. The absence of stone resources and partial
      burial by recent alluvial sediments has meant that these kinds of deposits have,
      until now, remained unidentified. We conducted core sampling, archaeological
      excavations and an interdisciplinary study of the stratigraphy and recovered
      materials from three shell midden mounds. Based on multiple lines of evidence,
      including radiocarbon dating, sedimentary proxies (elements, steroids and black
      carbon), micromorphology and faunal analysis, we demonstrate the anthropogenic
      origin and antiquity of these sites. In a tropical and geomorphologically active
      landscape often considered challenging both for early human occupation and for
      the preservation of hunter-gatherer sites, the newly discovered shell middens
      provide evidence for early to middle Holocene occupation and illustrate the
      potential for identifying and interpreting early open-air archaeological sites in
      western Amazonia. The existence of early hunter-gatherer sites in the Bolivian
      lowlands sheds new light on the region's past and offers a new context within
      which the late Holocene "Earthmovers" of the Llanos de Moxos could have emerged. 

PMID- 24013963
TI  - The challenges and future considerations regarding pregnancy-related outcomes in
      women with pre-existing diabetes.
AB  - Ineffective management of blood glucose levels during preconception and pregnancy
      has been associated with severe maternal and fetal complications in women with
      pre-existing diabetes. Studies have demonstrated that preconception counseling
      and pre-pregnancy care can dramatically reduce these risks. However, pregnancy
      related outcomes in women with diabetes continue to be less than ideal. This
      review highlights and discusses a variety of patient, provider, and
      organizational factors that can contribute to these suboptimal outcomes. Based on
      the findings of studies reviewed and authors' clinical and research experiences,
      recommendations have been proposed focusing on various aspects of care provided,
      including improved accessibility to effective preconception and pregnancy-related
      care and better organized clinic consultations that are sensitive to women's
      diabetes and pregnancy needs. 

PMID- 24013965
TI  - Commentary: Pediatric obesity: systems science strategies for prevention.
AB  - OBJECTIVES: Pediatric obesity is a major public health problem that undermines
      the physical and mental health of children and increases their risk for adult
      obesity and other chronic illnesses. Although health care providers, including
      pediatric psychologists, have implemented prevention programs, effects have been
      minimal, with no solid evidence of sustainable programs. METHODS: A systems
      science framework that incorporates the multiple interacting factors that
      influence pediatric obesity may be useful in guiding prevention. RESULTS: The
      National Prevention Strategy provides recommendations that can be incorporated
      into systems science designs, including (1) Healthy and Safe Environments, (2)
      Clinical and Community Preventive Services, (3) Empowering People, and (4)
      Elimination of Health Disparities. In addition, our recommendation is that future
      obesity prevention programs target early in life (pre-pregnancy through
      toddlerhood) and use multilevel multidisciplinary designs. CONCLUSIONS: The
      benefits of preventing pediatric obesity extend from the health and well-being of
      individual children to the economic security of the nation.

PMID- 24013967
TI  - Pantoea beijingensis sp. nov., isolated from the fruiting body of Pleurotus
      eryngii.
AB  - Four Gram-negative-staining, facultatively anaerobic bacterial isolates were
      obtained from a fruiting body of the edible mushroom Pleurotus eryngii showing
      symptoms of soft rot disease in Beijing, China. Partial 16S rRNA gene sequencing,
      together with partial rpoB sequencing, placed these isolates in the genus
      Pantoea. Multilocus sequence analysis based on the partial sequences of gyrB,
      rpoB, infB and atpD revealed Pantoea dispersa and Pantoea gaviniae as their
      closest phylogenetic relatives and indicated that these isolates constituted a
      possible novel species. DNA-DNA hybridization studies confirmed the
      classification of the new isolates as a novel species and phenotypic tests
      allowed for differentiation from the closest phylogenetic neighbours. The name
      Pantoea beijingensis sp. nov. [type strain LMG 27579(T) = KCTC 32406(T) =
      JZB2120001(T) (deposited at Institute of Plant and Environment Protection,
      Beijing Academy of Agriculture and Forestry Sciences)] is proposed.

PMID- 24013966
TI  - Patterns and predictors of paternal involvement in early adolescents' type 1
      diabetes management over 3 years.
AB  - OBJECTIVE: To document trajectories of paternal involvement in diabetes
      management and examine bidirectional associations with diabetes outcomes across
      early adolescence. METHODS: 3-year prospective assessment of paternal
      involvement, diabetes self-management, and glycemic control among 136 youth (age
      9-12 at baseline) and their mothers and fathers. RESULTS: Unconditional growth
      curves demonstrated decreasing amount (maternal report: F(1,128) = 14.79;
      paternal report: F(1,111) = 12.95, ps < 0.01) and level of contribution (maternal
      report: F(1,131) = 23.6, p < .01) of paternal involvement. Controlling for
      covariates, lower youth self-management predicted an increasing slope in fathers'
      self-reported amount of involvement (b = -0.15 to -0.22, p < .05), and higher
      levels of fathers' self-reported level of contribution predicted a decreasing
      slope in youths' self-reported self-management (b = -0.01, p < .05). CONCLUSIONS:
      Like mothers, fathers' involvement declines modestly during early adolescence.
      Different aspects of paternal involvement influence or are influenced by youths'
      self-management. Communication about ways to enhance fathers' involvement before
      this transition may help prevent or reduce declining diabetes management and
      control common in adolescence.

PMID- 24013973
TI  - Pre-operative ultrasound identification of thyroiditis helps predict the need for
      thyroid hormone replacement after thyroid lobectomy.
AB  - OBJECTIVE: To evaluate whether pre-operative thyroiditis identified by ultrasound
      (US) could help predict the need for thyroid hormone replacement (THR) following
      thyroid lobectomy. METHODS: Data from patients who underwent thyroid lobectomy in
      2006-2011, were not taking THR pre-operatively, and had >=1 month of follow-up
      were reviewed retrospectively. THR was prescribed for relatively elevated thyroid
      stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was
      used to estimate the percentage of patients who required THR at 6, 12, 18, and 24
      months postoperatively, and Cox proportional hazards regression models were used
      to evaluate prognostic factors for requiring post-thyroid lobectomy THR. RESULTS:
      During follow-up, 45 of 98 patients required THR. Median follow-up among patients
      not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after
      thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI],
      15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at
      18 months (95% CI, 43-67%). On univariate analysis, significant prognostic
      factors for postoperative THR included a pre-operative TSH level >2.5 MU
      international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004)
      and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005).
      Patients with both pre-operative TSH >2.5 MUIU/mL and US-identified thyroiditis
      had a 5.8-fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9;
      P<.0001). CONCLUSION: A pre-operative TSH level >2.5 MUIU/mL significantly
      increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add
      to that prediction and guide pre-operative patient counseling and surgical
      decision making. US-identified thyroiditis should be reported and post-thyroid
      lobectomy patients followed long-term (>=18 months).

PMID- 24013974
TI  - Cushing disease revealed by bilateral atypical central serous chorioretinopathy:
      case report.
AB  - OBJECTIVE: We report the case of a patient with Cushing disease revealed by
      bilateral central serous chorioretinopathy (CSCR). METHODS: We present the
      clinical history, physical findings, laboratory results, and imaging studies of a
      53-year-old Chinese woman with a Cushing disease revealed by bilateral CSCR. The
      association with CSCR and the pertinent literature are reviewed. RESULTS: A 53
      year-old patient initially presented to the Department of Ophthalmology with a 4
      week history of decreased vision in the left eye. Standard ophthalmologic
      examination and fluorescein angiography established the diagnosis of bilateral
      CSCR. Systemic clinical signs and biochemical analysis indicated
      hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary gland showed
      a left-side lesion compatible with a microadenoma. The diagnosis of
      Adrenocorticotropic hormone (ACTH)-dependent Cushing syndrome secondary to a
      pituitary microadenoma was selected. Endoscopic endonasal transsphenoidal surgery
      was performed and the pituitary adenoma was successfully removed. The histology
      confirmed the presence of ACTH-immunopositive pituitary adenoma. Early
      postoperative morning cortisol levels indicated early remission. At 6 weeks
      postoperatively, the patient's morning cortisol remains undetectable, and serous
      retinal detachments had regressed. CONCLUSION: CSCR is an uncommon manifestation
      of endogenous Cushing syndrome. It can be the first presentation of
      hypercortisolism caused by Cushing disease. CSCR should be considered when
      assessing patients with Cushing syndrome complaining of visual disorders. On the
      other hand, it is useful in patients with an atypical form of CSCR to exclude
      Cushing's syndrome.

PMID- 24013975
TI  - Variability in quantitative expression of receptors in nonfunctioning pituitary
      macroadenomas--an opportunity for targeted medical therapy.
AB  - OBJECTIVE: The surgical removal of a nonfunctioning pituitary macroadenoma (NFP
      Mac) is often incomplete. The appropriate treatment of recurrent/residual NFP
      Macs is not well established. Our objective was to detect and quantify receptors
      that may serve as potential targets for medical therapy for NFP-Macs with
      postsurgical residuals. METHODS: Several classes of pituitary receptors were
      analyzed by quantitative reverse transcriptase-polymerase chain reaction in 17
      adult NFP-Mac patients who underwent surgery. RESULTS: The median age was 50
      years, and 76% of patients were male. On magnetic resonance imaging, the mean NFP
      Mac diameter was 3.3 +/- 1.02 cm. Somatostatin receptor (SSTR) and dopamine
      receptor (DR) subtypes were found in almost all tumors. Based on previous
      studies, we postulated a cutoff of >= 2,000 receptor copies at which a response
      to therapy may occur. This cutoff was found in SSTR3 in 3 patients, SSTR2 in 2
      patients, SSTR1 and SSTR5 in 1 patient each, DR(2_total) in 13 patients,
      DR(2_short) (considered the most responsive to dopamine agonists) in 10 patients,
      and DR(2_long), DR5, DR4, and DR1 in 7, 3, 2, and 1 patient, respectively. Tumor
      size, invasiveness score, immunochemistry, gender, age, clinical symptoms, and
      postoperative residual tumor growth did not correlate with the type or copy
      number of receptor mRNAs. CONCLUSION: NFP-Macs with significant postsurgical
      tumor residuals contain several DR and SSTR subtypes, some with high copy
      numbers. The receptor composition of NFP-Macs may guide future clinical research
      into targeted treatment strategies to reduce residual tumor volume. Such studies
      would determine the potential threshold of receptor levels for response to
      therapy for existing dopaminergic agonists and somatostatin analogs.

PMID- 24013976
TI  - Long-term follow-up of patients on drug holiday from bisphosphonates: real-world
      setting.
AB  - OBJECTIVE: Atypical femoral fractures and osteoporosis of the jaw have been
      associated with prolonged bisphosphonate therapy for postmenopausal osteoporosis.
      American Association of Clinical Endocrinologists guidelines suggest a drug
      holiday after 4 to 5 years of bisphosphonate treatment for moderate-risk patients
      and 10 years for high-risk patients, but there are minimal data on safe holiday
      durations. A recent U. S. Food and Drug Administration perspective suggests a
      treatment duration of 3 to 5 years. Our aim was to describe a group of patients
      on drug holiday and identify fracture risk. METHODS: A retrospective chart review
      was conducted of 209 patients who started a bisphosphonate drug holiday between
      2005 and 2010. Collected data included bone mineral density (BMD), markers of
      bone turnover, vitamin D status, and clinical and radiographic reports of
      fractures. RESULTS: Eleven of 209 patients (5.2%) developed a fracture. Their
      mean age was 69.36 years (+/-15.58), and the mean lumbar spine and femoral neck T
      scores were -2.225 (+/-1.779) and -2.137 (+/-0.950), respectively. All patients
      had a significant increase in bone-specific alkaline phosphatase at 6 months,
      which was more pronounced in the fracture group (3.0 +/- 0.6083 MUg/L vs. 1.16 +/
      1.9267 MUg/L). Over 4 years, there was no significant change in mean lumbar
      spine BMD for the entire cohort, but there was a statistically significant
      decline in the femoral neck BMD at year 2 (-0.0084 +/- 0.03 gm/cm2). CONCLUSION:
      The current practice of initiating BP holidays needs further evaluation,
      particularly in the real-world setting. Elderly patients and those with very low
      BMD warrant close follow-up during a drug holiday. A fracture, early significant
      rise in bone turnover markers, and/or a decline in BMD should warrant resumption
      of osteoporosis therapy.

PMID- 24013977
TI  - Is above age 45 appropriate for upstaging well-differentiated papillary thyroid
      cancer?
AB  - OBJECTIVE: Age greater than 45 years old is a prognostic marker in well
      differentiated papillary thyroid cancer (PTC) using the American Joint Cancer
      Committee/Union Internationale Contre le Cancer Tumor Nodes Metastasis (AJCC/UICC
      TNM) staging system. Our clinical observation has been that patients aged 45 to
      64 years have similar outcomes when compared to patients younger than 45 years,
      and we questioned the origin and accuracy of this prognostic variable. METHODS:
      Using SEERstat software, we analyzed the Surveillance, Epidemiology, and End
      Result (SEER) database for PTC using the following International Classification
      of Diseases for Oncology (ICD-O) codes: 8050, 8260, 8340, 8341, 8342, 8243, and
      8344. Data were stratified in 5-year categories by age at diagnosis from 20 to 84
      years old, with patients 85 years old and above categorized together. Survival is
      reported as cause specific. RESULTS: A total of 53,581 patients were identified.
      The 5-year survival rate decreased with each increasing age category with no
      inflection point at age 45 in the survival curve. While the prognosis was less
      favorable in each advancing age group, survival remained above 90% for all age
      groups under 65 years. CONCLUSION: A review of the literature reveals a lack of
      data supporting the use of age 45 as a prognostic variable. Our SEER database
      review revealed a continuum of disease-specific mortality for each incremental 5
      year time period above age 45. We conclude that the current use of age 45 as a
      single prognostic age marker does not accurately reflect the progressive
      mortality risk that is apparent with each 5-year increment in age.

PMID- 24013978
TI  - Regional differences in thyroid cancer presentation and survival: a SEER study.
AB  - OBJECTIVE: The incidence of thyroid cancer has been steadily increasing. Several
      studies have identified gender and racial/ethnic differences in the incidence and
      prognosis of thyroid cancer. In this study, we sought to determine if the stage
      of presentation and survival rate of patients with thyroid cancer in the United
      States is affected by geographic region. METHODS: Using the Surveillance,
      Epidemiology, and End Results (SEER) database, we identified 100,404 patients
      diagnosed with thyroid cancer from 1973 through 2009. We assessed historical
      stage of diagnosis and cancer-free survival rate according to geographic region.
      To compare stages of diagnosis, we used multinomial logistic regression. To
      compare survival rates, we used Cox proportional hazards regression. Models were
      adjusted for age, year of diagnosis, cancer type, registry site, race/ethnicity,
      and stage. RESULTS: Of 100,404 patients, 52,902 (52.7%) were from the West,
      17,915 (17.8%) from the East, 15,302 (15.2%) from the South, and 14,285 (14.2%)
      from the Midwest. Overall, most patients presented with localized disease. Those
      from the West had a higher risk of presenting with regional and distant
      metastases. When we double-stratified by cancer subtype and racial group, we
      found no significant associations between geographic region and cancer-free
      survival rate. CONCLUSION: The presentation stage and survival rate of patients
      with thyroid cancer differs by geographic region, but not within separate
      racial/ethnic groups.

PMID- 24013979
TI  - Secondary parathyromatosis in a patient with normal kidney function: review of
      diagnostic modalities and approaches to management.
AB  - OBJECTIVE: To present a patient with secondary parathyromatosis, a rare
      complication of parathyroidectomy, and to discuss issues currently pertinent to
      its diagnosis and management. METHODS: Data were derived from clinical and
      pathologic observations obtained during patient care. RESULTS: The index patient
      developed intractable hyperparathyroidism and hypercalcemia that has persisted
      after 4 surgical procedures and has remained largely resistant to medication,
      albeit with partial amelioration with combined bisphosphonate and cinacalcet.
      CONCLUSION: Despite the rarity of this difficult complication of
      parathyroidectomy, its iatrogenic basis emphasizes a need for heightened
      awareness and caution among surgeons and endocrinologists. Herein we report an
      instance of intractable secondary parathyromatosis in a patient with normal
      kidney function, and we review current approaches to diagnosis and management.

PMID- 24013980
TI  - Amiodarone-induced thyrotoxicosis in adults with congenital heart disease-
      clinical presentation and response to therapy.
AB  - OBJECTIVE: The development of amiodarone-induced thyrotoxicosis (AIT) can
      threaten the hemodynamic stability of adult patients with congenital heart
      disease (CHD). Here, we describe the natural history and treatment response of
      AIT in this at-risk population. METHODS: We studied retrospectively all cases of
      AIT that occurred in CHD patients at our institution after a minimum of 3 months
      on amiodarone. Subjects were identified from the cohort of adults with CHD who
      were treated at the Mayo Clinic Adult CHD clinic between 1987 and 2009. RESULTS:
      We identified 23 cases of AIT: 7 were type 1, 13 were type 2, and 3 were
      undefined due to insufficient data. Most patients were symptomatic (17 of 23,
      74%), with arrhythmia and weight loss as the most common symptoms. The majority
      (12 of 23, 52%) were initially observed; 10 patients (43%) were treated medically
      and 1 patient (5%) underwent thyroidectomy. Four patients from the observation
      group eventually required active treatment and 3 patients from the medical group
      required surgery. Asymptomatic patients tended to resolve under observation (5 of
      7, 71.4%) rather than progress to active treatment (0 of 4) (P = .06).
      Discontinuation of amiodarone, AIT type, or use of perchlorate did not impact AIT
      duration. CONCLUSION: AIT in CHD patients exhibits a wide range of severity and
      sensitivity to medical therapy. Asymptomatic patients display a trend toward AIT
      resolution with observation alone. Amiodarone continuation does not appear to
      impact management outcome or disease duration. Additional studies in this high
      risk population could identify elements of pathophysiology that would point
      toward better disease prevention and treatment.

PMID- 24013981
TI  - Diabetes duration and the efficacy and safety of insulin glargine versus
      comparator treatment in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: To evaluate the effect of diabetes duration on efficacy and safety in
      patients with type 2 diabetes mellitus (T2DM) using insulin glargine versus
      comparator (oral antidiabetic drugs [OADs], dietary changes, or other insulins).
      METHODS: Data were pooled from randomized controlled clinical trials conducted in
      adults with T2DM with at least 24-week treatment with insulin glargine or a
      comparator, where predefined insulin titration algorithms were utilized to
      achieve fasting plasma glucose (FPG) concentrations of <=100 mg/dL. Glycated
      hemoglobin A1C (A1C), FPG, and insulin dose and safety (hypoglycemia) outcomes
      were analyzed. RESULTS: Nine studies were included in the analysis of 2,930
      patients. Patients with shorter duration of diabetes were more likely to have
      greater reductions in A1C compared with those who had longer-duration disease
      (P<.0001). Disease duration did not affect change in FPG concentrations (P =
      .9017), but lower weight-adjusted insulin dose was correlated with longer
      duration disease (P<.0001). Patients with longer-duration diabetes had increased
      risks of symptomatic hypoglycemia, confirmed hypoglycemia (self-monitored blood
      glucose <50 mg/dL and <70 mg/dL), and nocturnal hypoglycemia (all P<.001). No
      significant relationship was found between severe hypoglycemia and duration of
      diabetes. However, treatment with insulin glargine lowered A1C values more
      effectively than comparator treatments with fewer hypoglycemic episodes.
      CONCLUSION: Patients with shorter-duration T2DM better achieved target A1C levels
      and had less hypoglycemia than those with longer disease duration. Insulin
      glargine was associated with reduced A1C and fewer hypoglycemic events than
      comparators, regardless of disease duration.

PMID- 24013982
TI  - Insulin stacking versus therapeutic accumulation: understanding the differences.
AB  - OBJECTIVE: The build-up in insulin levels following repeated injection of
      prandial insulin at close intervals--referred to as insulin stacking--can
      increase the risk of hypoglycemia. With the development of basal insulins with a
      half-life > 24 hours and a duration of action > 40 hours, clinicians may be
      concerned about stacking when these long-acting formulations are administered
      once daily. The objective of this review is to clarify the difference between
      inappropriate insulin stacking when shorter-acting insulin formulations are
      repeatedly used to correct hyperglycemia and the appropriate accumulation of long
      acting insulin formulations dosed to steady-state pharmacokinetic (PK) profiles.
      METHODS: Relevant literature on insulin stacking, glucose-clamp studies, and
      clinical studies of insulin, in conjunction with the clinical experience of the
      authors, were used to present an overview of insulin PK properties and the
      effects of appropriate and inappropriate dosing intervals on steady-state
      conditions and likely clinical outcomes. RESULTS: Clinical studies confirm
      theoretical PK principles showing that unwanted insulin stacking (excessive
      concentrations) for basal insulin can be avoided by following recommended dosing
      and titration algorithms. Long-acting basal insulins need more time to reach
      steady state than shorter-acting basal insulins but then show reduced peak-trough
      fluctuations, translating into more consistent biologic action over a 24-hour
      period. CONCLUSION: The unwanted stacking and consequent hypoglycemia that can
      occur when correctional doses of rapid-acting insulin are administered at close
      intervals does not occur when long-acting basal insulins are dosed in appropriate
      amounts and adjusted at appropriate time intervals (e.g., insulin stacking,
      insulin administration, diabetes, ultralong duration of action, hypoglycemia
      every three or more days), allowing for pharmacologic steady-state accumulation.

PMID- 24013984
TI  - A pregnant dilemma: primary hyperparathyroidism due to parathyromatosis in
      pregnancy.
AB  - OBJECTIVE: To describe an exceedingly rare case of parathyromatosis in pregnancy
      and the limited medical treatment options available for such cases that are
      refractory to surgery. METHODS: Case presentation and description of clinical
      course with brief review of the literature. RESULTS: A 21-year-old woman with a
      history of 3.5 gland parathyroidectomy presented with severe hyperemesis during
      her first trimester of pregnancy and was found to have primary
      hyperparathyroidism attributable to parathyromatosis. We describe the diagnostic
      and management dilemmas associated with this case, which included localization of
      the culprit lesions, a technically challenging surgical resection and subsequent
      medical management with cinacalcet when symptomatic hypercalcemia recurred during
      the third trimester. To our knowledge, this is only the third report of the
      successful use of cinacalcet during pregnancy, and the first case report of
      parathyromatosis presenting during pregnancy. CONCLUSION: Cinacalcet was used
      safely and effectively during the third trimester of pregnancy to treat
      symptomatic hypercalcemia due to parathyromatosis.

PMID- 24013983
TI  - Hypercalcemia secondary to gastrointestinal stromal tumors: parathyroid hormone
      related protein independent mechanism?
AB  - OBJECTIVE: Hypercalcemia is a common paraneoplastic manifestation of many
      malignancies like breast, ovarian, and squamous-cell cancers of head and neck;
      however, there have been only a few case reports of hypercalcemia associated with
      gastrointestinal stromal tumors (GISTs). We report a case of GIST presenting with
      hypercalcemia without any osseous metastasis and provide a literature review
      regarding the mechanisms of hypercalcemia and therapeutic strategies. METHODS: We
      present a report of case and a review of the relevant literature. RESULTS: A 52
      year-old woman with history of localized breast cancer in remission and a pelvic
      13 * 12 cm GIST with peritoneal, liver, and lung metastases presented with
      hypercalcemia of 14.3 mg/dL (8.5-10.5 mg/dL). Parathyroid hormone-related protein
      (PTHrP) was undetectable, intact parathyroid hormone (PTH) was appropriately low
      at 1 pg/mL (10-65 pg/mL), and 1,25 dihydroxy vitamin D (1,25 OH2 vit D) was
      elevated at 131 pg/mL (18-78 pg/mL) with normal renal function. Calcium responded
      transiently to tyrosine kinase inhibitor therapy and bisphosphonates but within a
      year, she expired due to tumor progression. CONCLUSION: GIST is a rare cause of
      hypercalcemia. In addition to PTHrP expression, direct tumor production of
      1,25(OH)2 vit D or 1-alpha hydroxylase enzyme resulting in activation of 25
      hydroxy vitamin D may be an alternative mechanism in GIST-related hypercalcemia.
      Therapy with tyrosine kinase inhibitors and bisphosphonates is recommended,
      though prognosis is poor. Further investigations are needed to characterize the
      etiology and management of hypercalcemia in these patients.

PMID- 24013985
TI  - Osteocalcin levels on oral glucose load in women being investigated for
      polycystic ovary syndrome.
AB  - OBJECTIVE: Osteocalcin (OC) might play a hormone-like role in energy metabolism
      and the regulatory circuit between the pancreas and osteoblasts. Effects of a 75
      g oral glucose tolerance test (OGTT) on total OC, undercarboxylated (ucOC), and
      carboxylated osteocalcin (cOC) in insulin-resistant (IR) and noninsulin-resistant
      (nIR) premenopausal women was evaluated, and the relationships of changes in OC,
      ucOC, and cOC with area under the curve (AUC) insulin and the Matsuda index were
      examined. METHODS: In this cross-sectional study, 105 premenopausal women
      underwent OGTT; 18 were IR (homeostatic model assessment of insulin resistance
      [HOMA-IR] > 2.6; (2 with type 2 diabetes, 2 with impaired glucose tolerance), and
      87 were nIR (3 with impaired glucose tolerance). Changes in total OC, ucOC, and
      cOC were evaluated 60 and 120 minutes after glucose loading. RESULTS: At
      baseline, IR subjects had significantly lower levels of total OC, cOC, and ucOC.
      In nIR women, total OC decreased by 19% from 18.0 ng/mL (14.5-24.7) at baseline
      to 14.6 ng/mL (10.9-17.8) after 120 minutes, ucOC decreased by 22% from 3.2 ng/mL
      (2.1-4.5) to 2.5 ng/mL (1.7-3.5), and cOC decreased by 26% from 14.9 ng/mL (12.1
      20.4) to 11.1 ng/mL (9.0-14.5) (P < .001, respectively). No significant decreases
      were noted in IR subjects. The declines in OC and cOC predicted AUCinsulin
      (DeltaOC: beta = 0.301, P = .001; DeltacOC: beta = 0.315, P < .001) and the
      Matsuda index (DeltaOC: beta = -0.235, P = .003; DeltacOC: beta = -0.245, P =
      .002). CONCLUSIONS: Glucose intake lowers levels of OC, ucOC, and cOC in nIR
      women, the extent of which predicts IR and insulin sensitivity in premenopausal
      women. OC parameters seem suppressed in IR women. There might be a differential
      osteoblast response to oral glucose in IR and nIR women, with OC reflecting this
      finding.

PMID- 24013987
TI  - Transient thyrotoxicosis following minimally invasive radio-guided
      parathyroidectomy.
AB  - OBJECTIVE: We report a case of thyrotoxicosis following minimally invasive
      parathyroidectomy. METHODS: Case report with literature review. RESULTS: A 70
      year-old woman with primary hyperparathyroidism developed thyrotoxicosis 2 weeks
      following minimally invasive radio-guided parathyroidectomy. A diagnosis of
      postparathyroidectomy transient thyrotoxicosis (PTT) was made after excluding
      other causes of thyrotoxicosis. The patient reverted back to a euthyroid state in
      4 weeks with conservative management. CONCLUSION: PTT should be considered in the
      differential diagnosis in patients developing features of thyrotoxicosis
      following parathyroidectomy.

PMID- 24013986
TI  - Glucose variability is an independent predictor of mortality in hospitalized
      patients treated with total parenteral nutrition.
AB  - OBJECTIVE: Hyperglycemia is associated with increased mortality in critically ill
      patients treated with total parenteral nutrition (TPN). The role of glucose
      variability (GV) in predicting outcomes in these patients is not known. METHODS:
      This retrospective study included medical and surgical patients receiving TPN in
      a community teaching hospital. GV was calculated by standard deviation (SD) of
      blood glucose (BG) values and by mean BG daily (Delta) change (daily max - daily
      minimum). RESULTS: A total of 276 medical and surgical patients (mean age: 51 +/-
      18 years), 19% with a history of diabetes mellitus (DM), and 74% with intensive
      care unit (ICU) admission were treated with TPN. During TPN, the mean daily BG
      was 142.9 +/- 33 mg/dL; frequencies of hypoglycemia < 70 and < 40 mg/dL were 41%
      and 3%, respectively; and hospital mortality was 27.2%. The mean GV by SD was 38
      +/- 21 mg/dL and by mean (D) change 58 +/- 34 mg/dL. GV was significantly higher
      in deceased patients (SD: 48 +/- 25 vs. 34 +/- 18 mg/dL and Delta change: 75 +/-
      39 vs. 51 +/- 29 mg/dL, both P < .01) than surviving patients. Multivariate
      analysis adjusted for age, DM status, gender, APACHE (Acute Physiology and
      Chronic Health Evaluation) score, mean daily glucose, and hypoglycemia revealed
      that GV was an independent predictor of hospital mortality (P < .05). The
      association between GV and mortality was limited to patients without a history of
      DM and was not present in patients with DM. CONCLUSION: High GV is associated
      with increased hospital mortality independent of the presence and severity of
      hyperglycemia or hypoglycemia during TPN therapy. Prospective randomized trials
      are needed to determine if reduction in GV with intensive glycemic control
      improves clinical outcomes in patients treated with TPN.

PMID- 24013988
TI  - Evaluation of epicardial fat tissue thickness in patients with primary
      hyperparathyroidism.
AB  - OBJECTIVE: Primary hyperparathyroidism (pHPT) affects the cardiovascular system,
      and epicardial fat tissue (EFT) thickness is closely associated with
      cardiovascular diseases and atherosclerosis. Despite this, the association
      between EFT thickness and pHPT has not been studied in a clinical setting. This
      study aimed to assess EFT thickness in patients with pHPT. METHODS: The study
      included 38 patients with pHPT and 40 healthy controls. EFT thickness, carotid
      intima-media thickness (CIMT), serum levels of parathormone (PTH) and calcium,
      and blood chemistry profiles were determined in all subjects. Correlation and
      regression analyses were performed with EFT thickness and CIMT as dependent
      variables and age; systolic and diastolic blood pressure; body mass index (BMI);
      presence of diabetes mellitus; and free plasma glucose (FPG), PTH, and serum
      calcium (Ca) levels as independent variables. RESULTS: Both the mean EFT
      thickness and the mean CIMT were significantly greater in the pHPT group than the
      control group (P < .001 for both). Correlation analysis showed that EFT thickness
      was significantly correlated with CIMT, age, systolic blood pressure, and PTH and
      serum Ca levels. Furthermore, the regression analysis revealed that EFT thickness
      retained its independent and positive association with FPG and serum Ca levels.
      CONCLUSIONS: The results of this study indicate that EFT thickness may be a
      useful marker of early atherosclerosis in patients with pHPT. Furthermore, the
      increase in EFT thickness appears to be due to hypercalcemia.

PMID- 24013989
TI  - Three cases of dermatomyositis associated with papillary thyroid cancer.
AB  - OBJECTIVE: Dermatomyositis (DM) is considered a paraneoplastic phenomenon and
      cancer may precede or follow the development of clinical features by several
      years. Despite the prevalence of thyroid cancer, reports of an association are
      rare. We report 3 cases of dermatomyositis and thyroid cancer, focusing on the
      clinical course of the rheumatologic condition following thyroidectomy. We also
      performed a comprehensive review of the current literature. METHODS: We performed
      a chart review between 1960 and 2012 to identify patients with DM and papillary
      thyroid cancer (PTC) seen in Mayo Clinic, Rochester, in Minnesota, a tertiary
      referral center. Only 3 patients were identified using the above criteria.
      RESULTS: There was a significant improvement in the course of the dermatological
      condition after definitive treatment for thyroid cancer (i.e. thyroidectomy) in
      one of our patients. The risk of a first malignancy is highest at the time the
      diagnosis of dermatomyositis is made and remains significantly higher in the
      first two years following diagnosis. A comprehensive literature review identified
      only two patients with PTC and dermatomyositis (both in Taiwan) across 4
      international population cohorts. In addition, several cases have been reported
      from patients in the Far East, a geographical predilection that is unexplained.
      CONCLUSIONS: Our case series highlights the uncommon association between thyroid
      cancer and dermatomyositis while illustrating prevailing knowledge about the
      temporal relationship between dermatomyositis and thyroid cancer. Increased
      vigilance for and treatment of thyroid cancer in patients with dermatomyositis
      may assist in the successful management of this difficult rheumatologic
      condition.

PMID- 24013990
TI  - Real-world insulin treatment persistence among patients with type 2 diabetes.
AB  - OBJECTIVE: To evaluate real-world treatment persistence among patients with type
      2 diabetes mellitus (T2DM) initiating treatment with insulin. METHODS: Patient
      level data were pooled from 3 previously published observational retrospective
      studies evaluating patients with T2DM who were previously on oral antidiabetic
      drugs (OADs) and initiated with a basal analog insulin (insulin glargine or
      insulin detemir). Treatment persistence was defined as remaining on the study
      drug during the 1-year follow-up period without discontinuation or switching
      after study drug initiation. Analyses were conducted to identify baseline factors
      associated with persistence with insulin therapy and to estimate the association
      between insulin treatment persistence and patients' clinical and economic
      outcomes during the follow-up period. RESULTS: A total of 4,804 patients with
      T2DM (insulin glargine: n = 4,172, insulin detemir: n = 632) were included. The
      average insulin persistence rate over the 1-year follow-up period was 65.0%. A
      significantly higher persistence rate was associated with older age, initiation
      with insulin glargine using either disposable pens or vial-and-syringe, and with
      baseline exenatide or sitagliptin use. Higher insulin treatment persistence was
      also associated with lower hemoglobin A1c (A1C) at follow-up, a greater reduction
      in A1C from baseline, and lower health care utilization. CONCLUSION: In real
      world settings, treatment persistence among patients with T2DM initiating basal
      insulin is influenced by the type of insulin and patient factors. Greater insulin
      treatment persistence is linked to improved clinical outcomes and reduced health
      care utilization.

PMID- 24013991
TI  - Third-generation ELISA thyrotropin-receptor antibody levels as an adjuvant tool
      to guide management of patients with Graves orbitopathy.
AB  - OBJECTIVE: When assessing patients with Graves orbitopathy (GO) in an
      endocrinology outpatient setting, it is desirable to have a diagnostic laboratory
      tool to complement the clinical activity score (CAS) in distinguishing patients
      with moderate-severe active GO requiring high-priority ophthalmological care from
      those with mild or inactive GO who can be electively scheduled and to asses
      response to treatment. METHODS: A retrospective study was conducted to evaluate
      the correlation between thyrotropin-receptor antibody (TRAb)-Fast-enzyme-linked
      immunosorbent assay (ELISA) results and CAS in patients with GO seen at a
      tertiary referral center between 2000 and 2009. TRAb levels were quantified using
      a commercial third-generation TRAb-specific ELISA. Other variables analyzed
      included smoking status, gender, age, and thyroid-stimulating hormone level.
      RESULTS: Fifty-five patients with GO had a documented CAS within a mean of 22
      days from the recorded TRAb level determined by TRAb-Fast-ELISA. An increase in
      TRAb-Fast-ELISA of 1 unit was associated with a 15% (95% confidence interval, 7
      24%) increase in the odds ratio of elevated CAS. A TRAb-Fast-ELISA result >=10 as
      a diagnostic tool to predict a CAS >=3 was assessed and was found to have a
      specificity of 86.7% and a sensitivity of 87.2% for moderately severe GO.
      CONCLUSION: Our results demonstrate the ability to predict a patient's GO
      activity level by antibody titer. A TRAb-Fast-ELISA result >=10 can be used as a
      complementary diagnostic tool to predict a CAS >=3.

PMID- 24013992
TI  - Effect of the preoperative use of dopamine agonists in the postoperative course
      of prolactinomas: a systematic review.
AB  - OBJECTIVE: Since the 1980s, it has been discussed whether the preoperative
      treatment of prolactinomas with dopamine agonists (DAs) is beneficial or
      detrimental regarding postoperative residue or recurrence. Many neurosurgeons
      have emphasized the difficulties caused by fibrosis during the ablation of such
      prolactinomas. METHODS: From February to December 2012, the authors searched
      electronic databases and book chapters published from 1991 to 2012; a total of
      3,771 articles and 37 book chapters were searched. Ten articles that explicitly
      addressed this issue were identified. RESULTS: Five articles reported that
      preoperative treatment did not affect postoperative status. One article described
      a positive influence of preoperative treatment with DAs (P < .01), and 3 articles
      found a negative influence (P = .040, P = .02, no significance value reported).
      One article described histopathological evidence of tumor fibrosis that was found
      intraoperatively after preoperative DA treatment. CONCLUSIONS: This systematic
      review did not identify any strong evidence that preoperative treatment of
      prolactinomas with DAs is harmful or beneficial. Therefore, further studies are
      needed.

PMID- 24013993
TI  - Ectopic ACTH-secreting syndrome: a single-center experience.
AB  - OBJECTIVE: Ectopic adrenocorticotropic hormone (ACTH)-secreting syndrome (EAS) is
      a rare cause of ACTH-dependent endogenous hypercortisolism. The objective of this
      study was to analyze clinical, biochemical, and imaging characteristics;
      management strategies; and outcomes of EAS patients. METHOD: We screened the
      records (1993-2012) of ACTH-dependent endogenous hypercortisolism cases managed
      at a tertiary care center. RESULTS: Of the 218 patients, 17 were diagnosed with
      EAS. The median 8:00 AM serum cortisol was 36 MUg/dL (11.4-82.7 MUg/dL), and the
      median basal plasma ACTH was 156 pg/mL (53.5-468 pg/mL). Notably, ACTH levels
      below 100 pg/mL were found in 4 patients. Suspicious microadenoma was found on
      magnetic resonance imaging (MRI) of the pituitary in 5 patients, and all of them
      underwent transsphenoidal surgery (TSS). Inferior petrosal sinus sampling (IPSS)
      was performed in 8 patients, and the results were suggestive of a peripheral
      source in all 8. Computed tomography (CT) localized the lesion in 15/17 patients.
      In 2 patients with negative CTs, gallium DOTATATE positron emission tomography
      (PET) scans localized the lesion. Despite difficulties localizing bronchial
      carcinoids, the cure rate was high (72%). In contrast, thymic carcinoids were
      easily localized but had poor outcomes. CONCLUSION: EAS cannot be ruled out on
      the basis of marginally elevated ACTH. In cases with an equivocal MRI pituitary
      finding, prior IPSS can help avoid unnecessary TSS. CT is a useful modality for
      localization of an ectopic source. Functional imaging may help in cases where
      anatomical imaging fails.

PMID- 24013994
TI  - Clinical course and outcome of nonfunctioning pituitary adenomas in the elderly
      compared with younger age groups.
AB  - OBJECTIVE: Nonfunctioning pituitary adenomas (NFPAs) are the most common type of
      pituitary adenomas diagnosed in older patients. However, there are insufficient
      data regarding the clinical course, risk of regrowth, and long-term prognosis in
      elderly versus younger patients. METHODS: This retrospective cohort study
      observed 105 adult patients with NFPAs diagnosed between 1995 and 2012. Patients
      were stratified into 3 age groups: 18 to 44 years (29 patients), 45 to 64 years
      (38 patients), and 65 years and over (38 patients). The impact of age on
      presenting symptoms, disease course, and outcome was analyzed. RESULTS: Adenoma
      size was larger in patients <45 years (mean, 2.9 +/- 1.2 cm) compared to patients
      aged 45 to 64 years and those >=65 years old (2.3 +/- 0.9 and 2.5 +/- 0.8 cm,
      respectively; P = .05), with transsphenoidal surgery being the treatment of
      choice in all 3 groups (83, 92, and 84%, not significant). After a mean follow-up
      of 6 years, there were higher recovery rates from hypopituitarism in patients <45
      years old (58% vs. 27% and 24%; P = .04). Visual fields improved in most affected
      patients in each group following surgery (74, 94, and 86%), with a trend toward
      more full normalization in the youngest age group (58% vs. 44% and 41%; P = .09).
      There were no significant differences in the risk of remnant growth (29 to 39%),
      rates of radiation therapy, or need for repeated surgeries. There was no disease
      related mortality. CONCLUSION: Elderly patients with NFPA have lower rates of
      recovery from hypopituitarism after treatment compared to younger patients, but
      the rates of regrowth and need for salvage surgery are similar.

PMID- 24013995
TI  - Statistical transformation and the interpretation of inpatient glucose control
      data.
AB  - OBJECTIVE: To introduce a statistical method of assessing hospital-based non
      intensive care unit (non-ICU) inpatient glucose control. METHODS: Point-of-care
      blood glucose (POC-BG) data from hospital non-ICUs were extracted for January 1
      through December 31, 2011. Glucose data distribution was examined before and
      after Box-Cox transformations and compared to normality. Different subsets of
      data were used to establish upper and lower control limits, and exponentially
      weighted moving average (EWMA) control charts were constructed from June, July,
      and October data as examples to determine if out-of-control events were
      identified differently in nontransformed versus transformed data. RESULTS: A
      total of 36,381 POC-BG values were analyzed. In all 3 monthly test samples,
      glucose distributions in nontransformed data were skewed but approached a normal
      distribution once transformed. Interpretation of out-of-control events from EWMA
      control chart analyses also revealed differences. In the June test data, an out
      of-control process was identified at sample 53 with nontransformed data, whereas
      the transformed data remained in control for the duration of the observed period.
      Analysis of July data demonstrated an out-of-control process sooner in the
      transformed (sample 55) than nontransformed (sample 111) data, whereas for
      October, transformed data remained in control longer than nontransformed data.
      CONCLUSION: Statistical transformations increase the normal behavior of inpatient
      non-ICU glycemic data sets. The decision to transform glucose data could
      influence the interpretation and conclusions about the status of inpatient
      glycemic control. Further study is required to determine whether transformed
      versus nontransformed data influence clinical decisions or evaluation of
      interventions.

PMID- 24013996
TI  - Advanced bone age and hyperinsulinemia in overweight and obese children.
AB  - OBJECTIVE: In obese children, bone age (BA) tends to significantly exceed
      chronological age (CA). In vitro studies in mice suggest that insulin may
      directly modulate skeletal growth. We investigated whether there is an
      association between fasting insulin and BA maturation in obese children. METHODS:
      The study cohort comprised 74 overweight and obese children ages 4 to 13 years.
      BA divided by CA was used as an index for bone advancement. Participants were
      classified into tertiles based on their BA:CA ratio. Advanced BA maturation was
      defined as the third tertile, with BA:CA > 1.21. Components of the metabolic
      syndrome, including fasting insulin, fasting glucose, triglycerides, and high
      density lipoprotein (HDL) levels, were measured. RESULTS: Children with advanced
      BA were significantly younger, had a higher body mass index (BMI)-Z score (BMI
      Z), and were taller than children with bone advancement in the lower tertiles.
      Females had a 4.7-fold increased risk for advanced BA compared with males (95%
      confidence interval [CI], 1.29-17.1; P = .02). Children with a BMI-Z >= 1.96 and
      fasting insulin <= 30 MUU/L had a 3.6-fold increased risk of advanced BA (95% CI,
      1.00-12.8; P = 0.05). Moreover, hyperinsulinemia (fasting insulin > 30 MUU/L) was
      associated with a 6.8-fold increased risk for advanced BA, independent of the
      degree of obesity (95% CI, 1.45-32.1; P = .01). CONCLUSION: Marked
      hyperinsulinemia is associated with advanced BA in obese children. Insulin
      appears to modulate skeletal growth in humans.

PMID- 24013997
TI  - Adherence to growth hormone therapy: results of a multicenter study.
AB  - OBJECTIVE: To evaluate the adherence to growth hormone (GH) therapy and identify
      the influencing factors and outcomes in children. METHODS: A total of 217 GH
      naive patients in 6 pediatric endocrinology clinics were enrolled in the study.
      Structured questionnaires were filled out and patients were evaluated at the
      initiation and 3rd, 6th, and 12th months of therapy. Patients were categorized
      into 4 adherence segments based on percentage of doses omitted at each evaluation
      period, classified as excellent if 0%, good if 5%, fair if 5 to 10%, and poor if
      > 10%. RESULTS: There was a decrement in adherence to GH therapy during the study
      period (P = .006). Patients who showed excellent and good adherence to therapy
      had better growth velocity and growth velocity standard deviation scores (SDSs)
      (P = .014 and P = .015, respectively). A negative correlation between growth
      velocity SDS and number of missed injections was also observed (r = -.412; P =
      .007). A positive correlation between delta insulin-like growth factor-1 (IGF-1)
      SDS and growth velocity was demonstrated (r = .239; P = .042). IGF-1 levels were
      significantly higher in patients who showed excellent and good adherence to
      therapy (P = .01). Adherence was better in boys than in girls (P = .035), but
      adherence rates were not associated with age, cause of GH treatment,
      socioeconomic status, person who administered the injections, type of injection
      device, or GH product. CONCLUSION: Poor adherence to GH therapy was common in our
      group of patients and was one of the factors underlying suboptimal growth during
      therapy. Before considering other problems that can affect growth, clinicians
      should confirm good adherence to therapy.

PMID- 24013999
TI  - Care directed by a specialty-trained nurse practioner or physician assistant can
      overcome clinical inertia in management of inpatient diabetes.
AB  - OBJECTIVE: The study's objective was to determine the impact of care directed by
      a specialty-trained nurse practitioner (NP) or physician assistant (PA) on use of
      basal-bolus insulin therapy and glycemic control in a population of noncritically
      ill patients with diabetes. METHODS: A retrospective review of diabetes patients
      evaluated between July 1, 2011 and December 31, 2011 was conducted. Patients
      cotreated by a specialty-trained NP/PA were compared with patients who did not
      receive such care. RESULTS: In total, 171 patients with 222 hospitalizations were
      cotreated by an NP/PA and 543 patients with 665 hospitalizations were not.
      Patients with NP/PA involvement were younger, and had more frequent
      hyperglycemia, and had greater corticosteroid use than patients without NP/PA
      involvement (P<.01 for all). Basal-bolus insulin therapy was administered to 80%
      of patients with NP/PA involvement and 34% of patients without it (P<.01). After
      adjustment for age, sex, hyperglycemia measures, and corticosteroid use, the odds
      of basal-bolus insulin therapy being administered were increased significantly
      through NP/PA care (odds ratio, 3.66; 95% confidence interval, 2.36-5.67; P<.01).
      After adjustment for these variables and insulin regimen, NP/PA care was
      significantly correlated with lower mean point-of-care glucose levels at 24 hours
      before discharge (P = .042). CONCLUSION: Diabetes care assisted by an NP/PA
      trained in inpatient diabetes management results in greater use of recommended
      basal-bolus insulin therapy and is correlated with lower mean glucose levels
      before discharge. Adapting this model for use outside an endocrinology consult
      service needs to be explored so that the expertise can be brought to a broader
      inpatient population with diabetes.

PMID- 24014000
TI  - Primary hyperparathyroidism after laser therapy to the larynx.

PMID- 24014001
TI  - Andropause or male menopause? Rationale for testosterone replacement therapy in
      older men with low testosterone levels.
AB  - OBJECTIVE: To provide rationale for testosterone replacement therapy (TRT) in
      older men with low testosterone levels and symptoms consistent with testosterone
      deficiency. METHODS: The relevant literature was reviewed using PubMed. RESULTS:
      Cross-sectional and longitudinal population-based studies indicate that total and
      free testosterone levels fall with aging, and they may be accompanied by symptoms
      consistent with androgen deficiency. Testosterone treatment of younger men with
      very low testosterone levels and hypothalamic, pituitary, or testicular disease
      is associated with improvements in symptoms, body composition, bone density, and
      hematocrit/hemoglobin. Studies evaluating testosterone treatment of older men
      with low testosterone levels are limited, but they suggest some increase in fat
      free mass, some decrease in fat mass, and some increase in bone density of the
      lumbar spine and femoral neck. CONCLUSION: The Testosterone Trial should provide
      definitive information regarding the potential benefits of TRT in men >=65 years
      of age. If efficacy is confirmed, we will still need more information regarding
      the risks of TRT in older men.

PMID- 24014002
TI  - Over hypothyroidism in a woman undergoing controlled ovarian hyperstimulation.
AB  - OBJECTIVE: Thyroid function and gonadal axis are related throughout a woman's
      fertile period. Modifications of thyroid hormone levels have been reported as a
      consequence of controlled ovarian stimulation for infertility. METHODS: A 28-year
      old woman with regular menses and previous evidence of euthyroidism underwent
      controlled ovarian hyperstimulation (COH) for assisted reproductive technology
      (ART). Free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating
      hormone (TSH), and autoantibodies against thyroperoxidase and thyroglobulin
      (TPOAb and TgAb, respectively) were measured before COH. FT4, FT3, and TSH were
      re-evaluated 6 days, 2 weeks (during oocyte retrieval), and 1 month after the
      beginning of the procedure. RESULTS: The baseline evaluation revealed subclinical
      autoimmune hypothyroidism. The patient was hypothyroidic at 6 days and 2 weeks
      and spontaneously returned to euthyroidism 1 month after COH. CONCLUSION: This is
      the first case of a woman with an unknown subclinical autoimmune hypothyroidism
      who developed overt and transient hypothyroidism as a consequence of COH. Careful
      thyroid evaluation is advised for women undergoing COH.

PMID- 24014003
TI  - Association between subclinical hypothyroidism and blood pressure--a meta
      analysis of observational studies.
AB  - OBJECTIVE: This meta-analysis aimed to examine the relationship between
      subclinical hypothyroidism (SCH) and blood pressure (BP). METHODS: A systematic
      search of MEDLINE and EMBASE databases was performed to identify all related
      cross-sectional studies and baseline data in prospective cohort studies in the
      general population. Weighted mean differences (WMDs) of systolic blood pressure
      (SBP) and diastolic blood pressure (DBP) between SCH and euthyroid groups were
      calculated. Subgroup analyses and meta-regression were used to explore potential
      heterogeneities among studies. RESULTS: Twenty studies with 50,147 individuals
      were included. The WMDs of SBP and DBP were 1.47 mm Hg (95% confidence interval
      [CI] 0.54-2.39 mm Hg, P = .002) and 0.44 mm Hg [95% CI: -0.15-1.02 mm Hg, P =
      .142] between SCH and euthyroid groups, respectively. Significant heterogeneity
      was indentified among the included studies. Subgroup analysis showed that
      differences in study design, gender, and thyroid-stimulating hormone (TSH) cutoff
      level were not associated with the WMD of SBP, except for age difference between
      SCH and euthyroid groups. Meta-regression revealed a significant association
      between WMDs of SBP and age difference between the 2 groups (P = .015).
      CONCLUSION: In this meta-analysis, SCH was associated with slightly higher SBP,
      which could be attributed to the age difference between SCH and euthyroid groups
      in the general population. However, this study could not exclude an association
      between SCH and BP. Prospective studies are needed to confirm these findings.

PMID- 24014004
TI  - Visual vignette. Cabozantinib-induced hand-foot syndrome.

PMID- 24014005
TI  - TSH reference limits: new concepts and implications for diagnosis of subclinical
      hypothyroidism.

PMID- 24014006
TI  - Venous serum bicarbonate concentration predicts arterial pH in adults with
      diabetic ketoacidosis.
AB  - OBJECTIVE: The initial assessment of metabolic acidosis in subjects with diabetic
      ketoacidosis (DKA) is arterial blood gas analysis. This process is expensive,
      painful, and technically difficult. Furthermore, blood gas analysis may not be
      available in some facilities, especially in developing countries where DKA
      associated morbidity and mortality remain high. Therefore, we investigated the
      utility of venous bicarbonate concentration obtained from a basic metabolic panel
      in predicting arterial pH in adults with DKA. METHODS: We performed a
      retrospective analysis of clinical and biochemical data of 396 adults admitted to
      2 community teaching hospitals with DKA. We determined the correlation between
      arterial pH and venous serum parameters. Using multiple logistic regression, we
      obtained a predictive formula for arterial pH from serum venous bicarbonate
      level. RESULTS: The patient population was 59.0% male and had a mean age of 36.7
      +/- 13.3 years. We derived that arterial pH = 6.97 + (0.0163 x bicarbonate), and
      by applying this equation, we determined that serum venous bicarbonate
      concentration of <=20.6 mEq/L predicted arterial pH <=7.3 with over 95%
      sensitivity and 92% accuracy. CONCLUSION: Venous serum bicarbonate obtained from
      the basic metabolic panel is an affordable and reliable way of estimating
      arterial pH in adults with DKA. Validation of this formula in a prospective study
      would offer a more accessible means of estimating metabolic acidosis in adults
      with DKA, especially in developing countries where DKA incidence and mortality
      remain high.

PMID- 24014007
TI  - Plasma free metanephrine and normetanephrine levels are increased in patients
      with chronic kidney disease.
AB  - OBJECTIVE: Patients with impaired renal function, particularly those on dialysis,
      frequently exhibit high blood pressure and hemodynamic instability, which often
      lead to pheochromocytoma assessment. Our objective was to assess plasma free
      metanephrine (MN) and normetanephrine (NMN) in chronic kidney disease patients
      (CKD) with or without dialysis. METHODS: In this prospective observational study
      we performed enzyme-linked immunosorbent assays (ELISAs) to evaluate plasma free
      MN and NMN in 48 CKD patients (15 with stage 3-5 CKD without dialysis, 26 on
      hemodialysis [HD], and 7 continuous ambulatory peritoneal dialysis [CAPD]), 30
      patients with histologically proven pheochromocytoma, and 43 hypertensive
      patients. Adrenal masses were ruled out by abdominal computed tomography (CT)
      scans in all CKD and control hypertensive patients. RESULTS: All 3 CKD groups
      (HD, CAPD, and CKD without dialysis) had significantly higher plasma free MN and
      NMN levels than the control hypertensive group (P<.0055). HD and CAPD patients
      had significantly lower plasma free NMN (P<.0055), but free MN levels were not
      significantly different than those observed in pheochromocytoma patients. In
      patients with HD, CAPD, and CKD without dialysis, plasma free MN and NMN were
      higher than manufacturer's upper limits of normal in 57.7% and 28.5%, 13.3% and
      61.5%, and 85.7% and 26.6%, respectively. Regression models showed that the
      number of dialysis years was significantly correlated with plasma free MN (r =
      0.615, P<.001) but not free NMN. CONCLUSION: Plasma free MN and NMN levels are
      frequently elevated in CKD patients, particularly in those on dialysis. Plasma
      free MN levels significantly overlap with the range in pheochromocytoma patients
      and correlate with the number of years on dialysis.

PMID- 24014008
TI  - Mody-3: novel HNF1A mutation and the utility of glucagon-like peptide (GLP)-1
      receptor agonist therapy.
AB  - OBJECTIVE: An estimated 1 to 2% of cases of diabetes mellitus have a monogenic
      basis; however, delayed diagnosis and misdiagnosis as type 1 and 2 diabetes are
      common. Correctly identifying the molecular basis of an individual's diabetes may
      significantly alter the management approach to both the patient and his or her
      relatives. We describe a case of mature onset diabetes of the young (MODY) with
      sufficient evidence to support the classification of a novel HNF1A (hepatocyte
      nuclear factor-1-alpha) mutation as a cause of MODY-3. METHODS: A 21-year-old
      Caucasian female presented to our office with a diagnosis of noninsulin-dependent
      diabetes mellitus (NIDDM) at age 10; glycemia was initially managed with oral
      antidiabetic (OAD) agents and insulin detemir. The patient reported a strong
      family history of early-onset NIDDM in both her mother and maternal grandmother,
      both of whom eventually required insulin therapy to control glycemia. The
      patient's medical and family history were highly suggestive of maturity-onset
      diabetes of the young (MODY), and genetic testing was performed. RESULTS: Genetic
      screening detected a mutation p. Arg200Trp in the HNF1A gene in the patient, her
      mother, and maternal grandmother, suggesting a diagnosis of MODY-3. This finding
      resulted in a change of antidiabetic therapy in all 3 patients, including the
      addition of once-daily liraglutide therapy, which helped improve their glycemic
      control. CONCLUSION: Our case report supports the classification of the p.
      Arg200Trp mutation as a cause of MODY-3. The findings also suggest that glucagon
      like peptide-1 (GLP-1) receptor agonist therapy may be of value in managing
      glycemia in patients with MODY-3.

PMID- 24014009
TI  - Systemic treatment of gastroenteropancreatic neuroendocrine tumors (GEP-NETS):
      current approaches and future options.
AB  - OBJECTIVE: To describe recent advances in the treatment of gastroenteropancreatic
      neuroendocrine tumors (GEP-NETs). METHODS: A review of the published English
      language literature on GEP-NET therapy with a focus on practice-changing clinical
      trials. RESULTS: Somatostatin analog (SSA) treatment remains a cornerstone of GEP
      NET therapy, primarily for patients with hormonally functional tumors and midgut
      carcinoids. The biologic agents everolimus and sunitinib have similar tumor
      stabilizing effects in pancreatic NETs and are both approved to treat progressive
      low-intermediate-grade tumors. Their role in nonpancreatic NETs remains
      controversial. Cytotoxic chemotherapy is effective against pancreatic NETs, but
      modern prospective data is lacking. Radiolabeled SSAs will likely become more
      widely available once phase III randomized studies are completed. CONCLUSIONS:
      New treatment options for GEP-NETs have become available and highlight the
      necessity of developing predictive biomarkers that will allow for appropriate and
      individualized therapy selection.

PMID- 24014011
TI  - Neuroendocrine thymic carcinoma metastatic to the parathyroid gland that was
      reimplanted into the forearm in patient with multiple endocrine neoplasia type 1
      syndrome: a challenging management dilemma.
AB  - OBJECTIVE: To describe a unique case of a metastatic thymic carcinoma to the
      hyperplastic parathyroid gland and to present a challenging management dilemma.
      METHODS: Our patient is 60-year-old, intellectually disabled man with history of
      the multiple endocrine neoplasia type 1 (MEN1) syndrome, a surgery in 1985 for
      hypercalcemia with removal of one parathyroid gland, surgery in 2007 with
      findings of extensively necrotic well differentiated neuroendocrine carcinoma
      (carcinoid tumor) of the thymus. In 2012, he presented with persistent
      hypercalcemia (calcium level 11.7 mg/dL [range, 8.6-10.2]), and a parathyroid
      hormone (PTH) level of 225 pg/mL (range, 15-65 pg/mL). He underwent a repeat neck
      exploration with removal of 2 small inferior and a large left superior 4.5 * 2.5
      * 1.5 cm parathyroid glands, all of which showed hyperplasia on intraoperative
      frozen section. A small portion of the superior gland was reimplanted into the
      patient's forearm. Final pathology showed the presence of a focus of
      neuroendocrine tumor within the left superior parathyroid gland with immunostain
      identical to the thymic carcinoma. His postoperative PTH level was 14 pg/mL and
      calcium 8.5 mg/dL. A positron emission tomography-computed tomography (PET-CT)
      and octreotide scans revealed an extensive metastatic disease within the lung,
      mediastinum, and bones. RESULTS: We decided to leave a portion of the reimplanted
      parathyroid gland with possible metastatic thymic carcinoid in his forearm
      because of the presence a widespread metastatic disease and his intellectual
      disability that would result in noncompliance with calcium replacement in case of
      permanent hypocalcemia. CONCLUSION: Metastatic thymic carcinoma to the
      parathyroid gland has never been reported in the literature. We have described
      the first case and presented a challenging management dilemma.

PMID- 24014010
TI  - New tools for weight-loss therapy enable a more robust medical model for obesity
      treatment: rationale for a complications-centric approach.
AB  - OBJECTIVE: Recent advances in lifestyle intervention programs, pharmacotherapy,
      and bariatric surgery have enabled the development of medical models for the
      treatment of obesity. Regarding pharmacotherapy, in 2012 the U.S. Food and Drug
      Administration approved two new effective and safe weight-loss medications,
      phentermine/topiramate extended release and lorcaserin, which has greatly
      augmented options for medically assisted weight loss. METHODS: The rationale for
      advantages of a complications-centric medical model over current body mass index
      (BMI)-centric indications for therapy is examined. RESULTS: Currently, the
      baseline BMI level is the principle determinant of indications for obesity
      treatment using medication and surgery. However, the BMI-centric approach fails
      to target therapy to those obese patients who will benefit most from weight loss.
      In contrast, a complications-centric medical model is proposed that will earmark
      the modality and intensity of the therapeutic intervention based on the presence
      and severity of complications that can be ameliorated by weight loss. CONCLUSION:
      The complications-centric approach to "medicalizing" obesity care employs weight
      loss primarily as a tool to treat obesity-related complications and promotes the
      optimization of health outcomes, the benefit/risk ratio, and the cost
      effectiveness of therapy.

PMID- 24014012
TI  - IMPROVEMENT IN PANCREATIC beta-CELL FUNCTION WITH VITAMIN D AND CALCIUM
      SUPPLEMENTATION IN VITAMIN D-DEFICIENT NONDIABETIC SUBJECTS.
AB  - OBJECTIVE: There are varied reports on the effect of vitamin D supplementation on
      beta-cell function and plasma glucose levels. The objective of this study was to
      examine the effect of vitamin D and calcium supplementation on beta-cell function
      and plasma glucose levels in subjects with vitamin D deficiency. METHODS:
      Nondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D
      (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and
      intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency
      underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570
      international units [IU]/day; tolerable upper intake level, 10,000 IU/day;
      according to the Endocrine Society guidelines for vitamin D supplementation) and
      calcium (1 g/day) were supplemented. RESULTS: Thirty-seven patients with 25-OHD
      deficiency participated in the study. The baseline and post-vitamin D/calcium
      supplementation and the difference (corrected) were: serum calcium, 9 +/- 0.33
      and 8.33 +/- 1.09 mg/dL (-0.66 +/- 1.11 mg/dL); 25-OHD, 8.75 +/- 4.75 and 36.83
      +/- 18.68 ng/mL (28.00 +/- 18.33 ng/mL); PTH, 57.9 +/- 29.3 and 36.33 +/- 22.48
      pg/mL (-20.25 +/- 22.45 pg/mL); fasting plasma glucose, 78.23 +/- 7.60 and 73.47
      +/- 9.82 mg/dL (-4.88 +/- 10.65 mg/dL); and homeostasis model assessment-2
      percent beta-cell function C-peptide secretion (HOMA-2-%B C-PEP), 183.17 +/-
      88.74 and 194.67 +/- 54.71 (11.38 +/- 94.27). Significant differences were
      observed between baseline and post-vitamin D/calcium supplementation serum levels
      of corrected calcium (Z, -3.751; P<.0001), 25-OHD (Z, -4.9; P<.0001), intact PTH
      (Z, -4.04; P<.0001), fasting plasma glucose (Z, -2.7; P<.007), and HOMA-2-%B C
      PEP (Z, -1.923; P<.05) as determined by Wilcoxon signed rank test. Insulin
      resistance as measured by HOMA was unchanged. CONCLUSION: Optimizing serum 25-OHD
      concentrations and supplementation with calcium improves fasting plasma glucose
      levels and beta-cell secretory reserve. Larger randomized control studies are
      needed to determine if correction of 25-OHD deficiency will improve insulin
      secretion and prevent abnormalities of glucose homeostasis.

PMID- 24014013
TI  - Dr. John Shaw Billings: the surgeon general's librarian a historical vignette.

PMID- 24014015
TI  - False-positive FNA due to highly sensitive BRAF assay.
AB  - OBJECTIVE: False-positive BRAF analysis on fine-needle aspiration (FNA) has
      rarely been reported in the literature but may become more common with the advent
      of assays that can detect the BRAF V600E mutation in only 2% of otherwise wild
      type thyroid cells. We present the case of an indeterminate BRAF-positive FNA
      that showed no evidence of cancer on final surgical pathology. METHODS: Case
      report and literature review. RESULTS: An 87-year-old female with an
      indeterminate 1.7-cm nodule but BRAF-positive cytology underwent thyroid
      lobectomy. Final pathology revealed a benign adenomatoid nodule. An area rich in
      tumor cells from the nodule was identified, labeled, and microdissected for
      molecular testing, which demonstrated only wild-type BRAF, at the analytical
      limit of the assay. CONCLUSION: Increasingly sensitive BRAF assays using dual
      priming oligonucleotide-based multiplex polymerase chain reaction analysis can
      detect the BRAF V600E mutation when present in only 2% of a population of wild
      type cells. This increases the risk of false-positive results, particularly in
      cases of indeterminate FNA. Clinicians must caution patients in these
      circumstances that BRAF molecular testing may not have a 100% positive predictive
      value.

PMID- 24014014
TI  - Sarcoidosis.

PMID- 24014016
TI  - Visual vignette. Giant partially thrombosed left ophthalmic artery aneurysm.

PMID- 24014017
TI  - Testosterone therapy in older men with late-onset hypogonadism: a counter
      rationale.
AB  - OBJECTIVE: The past decade has seen a surge in referrals of older men for
      consideration of testosterone therapy for late-onset hypogonadism (LOH) to treat
      symptoms such as fatigue, sexual dysfunction and decreased vitality. Prescription
      sales of testosterone have accordingly increased by 20-fold over the same period,
      due mainly to marketing campaign as well as to the failure of clinicians to
      distinguish organic hypogonadism from LOH. This review seeks to provide a counter
      rationale for testosterone therapy in LOH. METHODS: A retrospective review of
      English-language epidemiologic studies, clinical trials and their relevant cited
      studies related to testosterone and older men was carried out. RESULTS:
      Shortcomings of population studies on LOH include use of multiple numeric
      definitions and non-standard testosterone assays, and measurement of testosterone
      at a single time point. In contrast to higher estimates of prevalence based
      solely on numeric values, the syndromic prevalence of LOH is only 2%. Although
      attrition of testicular Leydig cells and slowing of gonadotropin-releasing
      hormone neurons both contribute to LOH, obesity and other comorbidities strongly
      influence testosterone levels, suggesting that testosterone is a biomarker of
      health. Testosterone therapy in LOH has consistently resulted in improvements in
      muscle mass and strength, although data regarding effects on physical function
      and improvements in fall and fracture rates remain unknown. Eythrocytosis is the
      most common adverse effect of testosterone therapy in older men, while long-term
      risks in the prostate and cardiovascular system remain unclear. CONCLUSION:
      Considering the paucity of data on clinically meaningful outcomes, the number of
      uncertain risks, and the fact that modifiable risk factors adversely influence
      testosterone levels, healthy lifestyle and treatment of comorbidities might
      attenuate age-related declines in testosterone levels.

PMID- 24014018
TI  - The outer membrane TolC-like channel HgdD is part of tripartite resistance
      nodulation-cell division (RND) efflux systems conferring multiple-drug resistance
      in the Cyanobacterium Anabaena sp. PCC7120.
AB  - The TolC-like protein HgdD of the filamentous, heterocyst-forming cyanobacterium
      Anabaena sp. PCC 7120 is part of multiple three-component "AB-D" systems spanning
      the inner and outer membranes and is involved in secretion of various compounds,
      including lipids, metabolites, antibiotics, and proteins. Several components of
      HgdD-dependent tripartite transport systems have been identified, but the
      diversity of inner membrane energizing systems is still unknown. Here we
      identified six putative resistance-nodulation-cell division (RND) type factors.
      Four of them are expressed during late exponential and stationary growth phase
      under normal growth conditions, whereas the other two are induced upon incubation
      with erythromycin or ethidium bromide. The constitutively expressed RND component
      Alr4267 has an atypical predicted topology, and a mutant strain (I-alr4267) shows
      a reduction in the content of monogalactosyldiacylglycerol as well as an altered
      filament shape. An insertion mutant of the ethidium bromide-induced all7631 did
      not show any significant phenotypic alteration under the conditions tested.
      Mutants of the constitutively expressed all3143 and alr1656 exhibited a Fox(-)
      phenotype. The phenotype of the insertion mutant I-all3143 parallels that of the
      I-hgdD mutant with respect to antibiotic sensitivity, lipid profile, and ethidium
      efflux. In addition, expression of the RND genes all3143 and all3144 partially
      complements the capability of Escherichia coli DeltaacrAB to transport ethidium.
      We postulate that the RND transporter All3143 and the predicted membrane fusion
      protein All3144, as homologs of E. coli AcrB and AcrA, respectively, are major
      players for antibiotic resistance in Anabaena sp. PCC 7120. 

PMID- 24014019
TI  - Conformational plasticity and ligand binding of bacterial monoacylglycerol
      lipase.
AB  - Monoacylglycerol lipases (MGLs) play an important role in lipid catabolism across
      all kingdoms of life by catalyzing the release of free fatty acids from
      monoacylglycerols. The three-dimensional structures of human and a bacterial MGL
      were determined only recently as the first members of this lipase family. In
      addition to the alpha/beta-hydrolase core, they showed unexpected structural
      similarities even in the cap region. Nevertheless, the structural basis for
      substrate binding and conformational changes of MGLs is poorly understood. Here,
      we present a comprehensive study of five crystal structures of MGL from Bacillus
      sp. H257 in its free form and in complex with different substrate analogs and the
      natural substrate 1-lauroylglycerol. The occurrence of different conformations
      reveals a high degree of conformational plasticity of the cap region. We identify
      a specific residue, Ile-145, that might act as a gatekeeper restricting access to
      the binding site. Site-directed mutagenesis of Ile-145 leads to significantly
      reduced hydrolase activity. Bacterial MGLs in complex with 1-lauroylglycerol,
      myristoyl, palmitoyl, and stearoyl substrate analogs enable identification of the
      binding sites for the alkyl chain and the glycerol moiety of the natural ligand.
      They also provide snapshots of the hydrolytic reaction of a bacterial MGL at
      different stages. The alkyl chains are buried in a hydrophobic tunnel in an
      extended conformation. Binding of the glycerol moiety is mediated via Glu-156 and
      water molecules. Analysis of the structural features responsible for cap
      plasticity and the binding modes of the ligands suggests conservation of these
      features also in human MGL. 

PMID- 24014021
TI  - miR-1247 functions by targeting cartilage transcription factor SOX9.
AB  - microRNAs are a large and essential class of gene regulators that play key roles
      in development, homeostasis, and disease. They are necessary for normal skeletal
      development, and their expression is altered in arthritis. However, the specific
      role of individual microRNAs is only beginning to be unraveled. Using microRNA
      expression profiling in healthy human articular cartilage cells (chondrocytes),
      we identified miR-1247 expression as highly correlated with that of the
      differentiated cell phenotype. Transcribed from the DLK1-DIO3 locus, the function
      of miR-1247 is completely unknown. In mice its expression level was relatively
      high in cartilage tissue, and correlated with cartilage-associated microRNA miR
      675 across a range of 15 different mouse tissues. To further probe miR-1247
      function, overexpression and inhibition studies were performed in isolated human
      chondrocytes. Modulation of miR-1247 was found to exert profound phenotypic
      effects altering expression levels of cartilage master regulator transcription
      factor SOX9. SOX9 is essential for cartilage development and subsequent function
      throughout life, and mutations in this gene result in severe dwarfism. Putative
      miR-1247 binding sites were further investigated using luciferase reporter
      assays, which indicated binding of miR-1247 to a highly conserved region in the
      coding sequence of SOX9 but not in its 3'-UTR. Interestingly, depletion of SOX9
      in human chondrocytes resulted in increased levels of the mature, processed
      microRNA, suggesting a negative feedback loop between miR-1247 and its target
      SOX9. 

PMID- 24014020
TI  - O-Linked beta-N-acetylglucosamine (O-GlcNAc) regulates emerin binding to barrier
      to autointegration factor (BAF) in a chromatin- and lamin B-enriched "niche".
AB  - Emerin, a membrane component of nuclear "lamina" networks with lamins and barrier
      to autointegration factor (BAF), is highly O-GlcNAc-modified ("O-GlcNAcylated")
      in mammalian cells. Mass spectrometry analysis revealed eight sites of O
      GlcNAcylation, including Ser-53, Ser-54, Ser-87, Ser-171, and Ser-173. Emerin O
      GlcNAcylation was reduced ~50% by S53A or S54A mutation in vitro and in vivo. O
      GlcNAcylation was reduced ~66% by the triple S52A/S53A/S54A mutant, and S173A
      reduced O-GlcNAcylation of the S52A/S53A/S54A mutant by ~30%, in vivo. We
      separated two populations of emerin, A-type lamins and BAF; one population
      solubilized easily, and the other required sonication and included histones and B
      type lamins. Emerin and BAF associated only in histone- and lamin-B-containing
      fractions. The S173D mutation specifically and selectively reduced GFP-emerin
      association with BAF by 58% and also increased GFP-emerin hyper-phosphorylation.
      We conclude that beta-N-acetylglucosaminyltransferase, an essential enzyme,
      controls two regions in emerin. The first region, defined by residues Ser-53 and
      Ser-54, flanks the LEM domain. O-GlcNAc modification at Ser-173, in the second
      region, is proposed to promote emerin association with BAF in the chromatin/lamin
      B "niche." These results reveal direct control of a conserved LEM domain nuclear
      lamina component by beta-N-acetylglucosaminyltransferase, a nutrient sensor that
      regulates cell stress responses, mitosis, and epigenetics.

PMID- 24014022
TI  - Restoring the procofactor state of factor Va-like variants by complementation
      with B-domain peptides.
AB  - Coagulation factor V (FV) circulates as an inactive procofactor and is activated
      to FVa by proteolytic removal of a large inhibitory B-domain. Conserved basic and
      acidic sequences within the B-domain appear to play an important role in keeping
      FV as an inactive procofactor. Here, we utilized recombinant B-domain fragments
      to elucidate the mechanism of this FV autoinhibition. We show that a fragment
      encoding the basic region (BR) of the B-domain binds with high affinity to
      cofactor-like FV(a) variants that harbor an intact acidic region. Furthermore,
      the BR inhibits procoagulant function of the variants, thereby restoring the
      procofactor state. The BR competes with FXa for binding to FV(a), and limited
      proteolysis of the B-domain, specifically at Arg(1545), ablates BR binding to
      promote high affinity association between FVa and FXa. These results provide new
      insight into the mechanism by which the B-domain stabilizes FV as an inactive
      procofactor and reveal how limited proteolysis of FV progressively destabilizes
      key regulatory regions of the B-domain to produce an active form of the molecule.

PMID- 24014024
TI  - The nitric-oxide reductase from Paracoccus denitrificans uses a single specific
      proton pathway.
AB  - The NO reductase from Paracoccus denitrificans reduces NO to N2O (2NO + 2H(+) +
      2e(-) -> N2O + H2O) with electrons donated by periplasmic cytochrome c
      (cytochrome c-dependent NO reductase; cNOR). cNORs are members of the heme-copper
      oxidase superfamily of integral membrane proteins, comprising the O2-reducing,
      proton-pumping respiratory enzymes. In contrast, although NO reduction is as
      exergonic as O2 reduction, there are no protons pumped in cNOR, and in addition,
      protons needed for NO reduction are derived from the periplasmic solution (no
      contribution to the electrochemical gradient is made). cNOR thus only needs to
      transport protons from the periplasm into the active site without the requirement
      to control the timing of opening and closing (gating) of proton pathways as is
      needed in a proton pump. Based on the crystal structure of a closely related cNOR
      and molecular dynamics simulations, several proton transfer pathways were
      suggested, and in principle, these could all be functional. In this work, we show
      that residues in one of the suggested pathways (denoted pathway 1) are sensitive
      to site-directed mutation, whereas residues in the other proposed pathways
      (pathways 2 and 3) could be exchanged without severe effects on turnover activity
      with either NO or O2. We further show that electron transfer during single
      turnover reduction of O2 is limited by proton transfer and can thus be used to
      study alterations in proton transfer rates. The exchange of residues along
      pathway 1 showed specific slowing of this proton-coupled electron transfer as
      well as changes in its pH dependence. Our results indicate that only pathway 1 is
      used to transfer protons in cNOR. 

PMID- 24014023
TI  - Transgenic expression of microRNA-185 causes a developmental arrest of T cells by
      targeting multiple genes including Mzb1.
AB  - miR-185 is a microRNA (miR) that targets Bruton's tyrosine kinase in B cells,
      with reductions in miR-185 linked to B cell autoantibody production. In
      hippocampal neurons, miR-185 targets both sarcoplasmic/endoplasmic reticulum
      calcium ATPase 2 and a novel Golgi inhibitor. This miR is haploinsufficient in 90
      95% of individuals with chromosome 22q11.2 deletion syndrome, patients who can
      present with immune, cardiac, and parathyroid problems, learning disorders, and a
      high incidence of schizophrenia in adults. The reduced levels of miR-185 in
      neurons cause presynaptic neurotransmitter release. Many of the 22q11.2 deletion
      syndrome patients have a thymic hypoplasia, which results in a peripheral T cell
      lymphopenia and unusual T helper cell skewing. The molecular targets of miR-185
      in thymocytes are unknown. Using an miR-185 T cell transgenic approach,
      increasing levels of miR-185 attenuated T cell development at the T cell receptor
      beta (TCRbeta) selection checkpoint and during positive selection. This caused a
      peripheral T cell lymphopenia. Mzb1, Nfatc3, and Camk4 were identified as novel
      miR-185 targets. Elevations in miR-185 enhanced TCR-dependent intracellular
      calcium levels, whereas a knockdown of miR-185 diminished these calcium
      responses. These effects concur with reductions in Mzb1, an endoplasmic reticulum
      calcium regulator. Consistent with their haploinsufficiency of miR-185, Mzb1
      levels were elevated in thymocyte extracts from several 22q11.2 deletion syndrome
      patients. Our findings indicate that miR-185 regulates T cell development through
      its targeting of several mRNAs including Mzb1. 

PMID- 24014025
TI  - MCF-7 cells expressing nuclear associated lysyl oxidase-like 2 (LOXL2) exhibit an
      epithelial-to-mesenchymal transition (EMT) phenotype and are highly invasive in
      vitro.
AB  - LOXL2 is a copper- and lysine tyrosylquinone-dependent amine oxidase that has
      been proposed to function both extracellularly and intracellularly to activate
      oncogenic signaling pathways leading to EMT and invasion of breast cancer cells.
      In this study, we selected MCF-7 cells that stably express forms of recombinant
      LOXL2 differing in their subcellular localizations and catalytic competencies.
      This enabled us to dissect the molecular functions of intracellular and
      extracellular LOXL2s and examine their contributions to breast cancer
      metastasis/invasion. We discovered that secreted LOXL2 (~100-kDa) is N
      glycosylated at Asn-455 and Asn-644, whereas intracellular LOXL2 (~75-kDa) is
      nonglycosylated and N-terminally processed, and is primarily associated with the
      nucleus. Both forms of LOXL2 can oxidize lysine in solution. However, we found
      that expression of intracellular LOXL2 is more strongly associated with EMT and
      invasiveness than secreted LOXL2 in vitro. The results indicate that nuclear
      associated LOXL2 contributes to the stabilization of Snail1 transcription factor
      at the protein level to induce EMT and promote invasion in vitro, through
      repression of E-cadherin, occludin, and estrogen receptor-alpha, and up
      regulation of vimentin, fibronectin, and MT1-MMP.

PMID- 24014026
TI  - Characterization of the AtsR hybrid sensor kinase phosphorelay pathway and
      identification of its response regulator in Burkholderia cenocepacia.
AB  - AtsR is a membrane-bound hybrid sensor kinase of Burkholderia cenocepacia that
      negatively regulates quorum sensing and virulence factors such as biofilm
      production, type 6-secretion, and protease secretion. Here we elucidate the
      mechanism of AtsR phosphorelay by site-directed mutagenesis of predicted
      histidine and aspartic acid phosphoacceptor residues. We demonstrate by in vitro
      phosphorylation that histidine 245 and aspartic acid 536 are conserved sites of
      phosphorylation in AtsR, and we also identify the cytosolic response regulator
      AtsT (BCAM0381) as a key component of the AtsR phosphorelay pathway. Monitoring
      the function of AtsR and its derivatives in vivo by measuring extracellular
      protease activity and swarming motility confirmed the in vitro phosphorylation
      results. Together we find that the AtsR receiver domain plays a fine-tuning role
      in determining the levels of phosphotransfer from its sensor kinase domain to the
      AtsT response regulator. 

PMID- 24014027
TI  - p87 and p101 subunits are distinct regulators determining class IB
      phosphoinositide 3-kinase (PI3K) specificity.
AB  - Class IB phosphoinositide 3-kinase gamma (PI3Kgamma) comprises a single catalytic
      p110gamma subunit, which binds to two non-catalytic subunits, p87 or p101, and
      controls a plethora of fundamental cellular responses. The non-catalytic subunits
      are assumed to be redundant adaptors for Gbetagamma enabling G-protein-coupled
      receptor-mediated regulation of PI3Kgamma. Growing experimental data provide
      contradictory evidence. To elucidate the roles of the non-catalytic subunits in
      determining the specificity of PI3Kgamma, we tested the impact of p87 and p101 in
      heterodimeric p87-p110gamma and p101-p110gamma complexes on the modulation of
      PI3Kgamma activity in vitro and in living cells. RT-PCR, biochemical, and imaging
      data provide four lines of evidence: (i) specific expression patterns of p87 and
      p101, (ii) up-regulation of p101, providing the basis to consider p87 as a
      protein forming a constitutively and p101 as a protein forming an inducibly
      expressed PI3Kgamma, (iii) differences in basal and stimulated enzymatic
      activities, and (iv) differences in complex stability, all indicating apparent
      diversity within class IB PI3Kgamma. In conclusion, expression and activities of
      PI3Kgamma are modified differently by p87 and p101 in vitro and in living cells,
      arguing for specific regulatory roles of the non-catalytic subunits in the
      differentiation of PI3Kgamma signaling pathways. 

PMID- 24014028
TI  - Dynamic analysis of the epidermal growth factor (EGF) receptor-ErbB2-ErbB3
      protein network by luciferase fragment complementation imaging.
AB  - ErbB3 is a member of the ErbB family of receptor tyrosine kinases. It is unique
      because it is the only member of the family whose kinase domain is defective. As
      a result, it is obliged to form heterodimers with other ErbB receptors to signal.
      In this study, we characterized the interaction of ErbB3 with the EGF receptor
      and ErbB2 and assessed the effects of Food and Drug Administration-approved
      therapeutic agents on these interactions. Our findings support the concept that
      ErbB3 exists in preformed clusters that can be dissociated by NRG-1beta and that
      it interacts with other ErbB receptors in a distinctly hierarchical fashion. Our
      study also shows that all pairings of the EGF receptor, ErbB2, and ErbB3 form
      ligand-independent dimers/oligomers. The small-molecule tyrosine kinase
      inhibitors erlotinib and lapatinib differentially enhance the dimerization of the
      various ErbB receptor pairings, with the EGFR/ErbB3 heterodimer being
      particularly sensitive to the effects of erlotinib. The data suggest that the
      physiological effects of these drugs may involve not only inhibition of tyrosine
      kinase activity but also a dynamic restructuring of the entire network of
      receptors. 

PMID- 24014029
TI  - Ei24, a novel E2F target gene, affects p53-independent cell death upon
      ultraviolet C irradiation.
AB  - The deficiency of retinoblastoma (Rb) gene deregulates E2F transcription factors
      and thus induces E2F target genes directly or p53 target genes indirectly via
      mouse p19(Arf) (or p14(ARF) in humans), an E2F target gene. Here, we identified
      that etoposide-induced 2.4 mRNA (Ei24)/p53-induced gene 8 (Pig8), a p53 target
      gene involved in apoptosis and autophagy, was up-regulated in Rb(-/-) mouse
      embryonic fibroblasts (MEFs). The Ei24 promoter was activated by E2F1 via
      multiple E2F-responsive elements, independently of the previously reported p53
      responsive element. Chromatin immunoprecipitation assays revealed that E2F1
      directly acts on the mouse Ei24 promoter. We observed that Ei24 expression was
      suppressed in p53(-/-) MEFs upon UVC irradiation, which was exacerbated in p53(-/
      ) E2f1(-/-) MEFs, supporting the positive role of E2F1 on Ei24 transcription.
      Furthermore, Ei24 knockdown sensitized p53(-/-) MEFs against UVC irradiation.
      Together, our data indicate that Ei24 is a novel E2F target gene contributing to
      the survival of p53-deficient cells upon UVC irradiation and thus may have a
      potential significance as a therapeutic target of certain chemotherapy for
      treating p53-deficient tumors. 

PMID- 24014030
TI  - Assessing the conformational changes of pb5, the receptor-binding protein of
      phage T5, upon binding to its Escherichia coli receptor FhuA.
AB  - Within tailed bacteriophages, interaction of the receptor-binding protein (RBP)
      with the target cell triggers viral DNA ejection into the host cytoplasm. In the
      case of phage T5, the RBP pb5 and the receptor FhuA, an outer membrane protein of
      Escherichia coli, have been identified. Here, we use small angle neutron
      scattering and electron microscopy to investigate the FhuA-pb5 complex. Specific
      deuteration of one of the partners allows the complete masking in small angle
      neutron scattering of the surfactant and unlabeled proteins when the complex is
      solubilized in the fluorinated surfactant F6-DigluM. Thus, individual structures
      within a membrane protein complex can be described. The solution structure of
      FhuA agrees with its crystal structure; that of pb5 shows an elongated shape.
      Neither displays significant conformational changes upon interaction. The
      mechanism of signal transduction within phage T5 thus appears different from that
      of phages binding cell wall saccharides, for which structural information is
      available. 

PMID- 24014032
TI  - The thiamine biosynthetic enzyme ThiC catalyzes multiple turnovers and is
      inhibited by S-adenosylmethionine (AdoMet) metabolites.
AB  - ThiC (4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate synthase; EC
      4.1.99.17) is a radical S-adenosylmethionine (AdoMet) enzyme that uses a [4Fe
      4S](+) cluster to reductively cleave AdoMet to methionine and a 5'-deoxyadenosyl
      radical that initiates catalysis. In plants and bacteria, ThiC converts the
      purine intermediate 5-aminoimidazole ribotide to 4-amino-5-hydroxymethyl-2
      methylpyrimidine phosphate, an intermediate of thiamine pyrophosphate (coenzyme
      B1) biosynthesis. In this study, assay conditions were implemented that
      consistently generated 5-fold molar excess of HMP, demonstrating that ThiC
      undergoes multiple turnovers. ThiC activity was improved by in situ removal of
      product 5'-deoxyadenosine. The activity was inhibited by AdoMet metabolites S
      adenosylhomocysteine, adenosine, 5'-deoxyadenosine, S-methyl-5'-thioadenosine,
      methionine, and homocysteine. Neither adenosine nor S-methyl-5'-thioadenosine had
      been shown to inhibit radical AdoMet enzymes, suggesting that ThiC is distinct
      from other family members. The parameters for improved ThiC activity and turnover
      described here will facilitate kinetic and mechanistic analyses of ThiC. 

PMID- 24014031
TI  - Structure, folding dynamics, and amyloidogenesis of D76N beta2-microglobulin:
      roles of shear flow, hydrophobic surfaces, and alpha-crystallin.
AB  - Systemic amyloidosis is a fatal disease caused by misfolding of native globular
      proteins, which then aggregate extracellularly as insoluble fibrils, damaging the
      structure and function of affected organs. The formation of amyloid fibrils in
      vivo is poorly understood. We recently identified the first naturally occurring
      structural variant, D76N, of human beta2-microglobulin (beta2m), the ubiquitous
      light chain of class I major histocompatibility antigens, as the amyloid fibril
      protein in a family with a new phenotype of late onset fatal hereditary systemic
      amyloidosis. Here we show that, uniquely, D76N beta2m readily forms amyloid
      fibrils in vitro under physiological extracellular conditions. The globular
      native fold transition to the fibrillar state is primed by exposure to a
      hydrophobic-hydrophilic interface under physiological intensity shear flow. Wild
      type beta2m is recruited by the variant into amyloid fibrils in vitro but is
      absent from amyloid deposited in vivo. This may be because, as we show here, such
      recruitment is inhibited by chaperone activity. Our results suggest general
      mechanistic principles of in vivo amyloid fibrillogenesis by globular proteins, a
      previously obscure process. Elucidation of this crucial causative event in
      clinical amyloidosis should also help to explain the hitherto mysterious timing
      and location of amyloid deposition. 

PMID- 24014033
TI  - RNA recognition by the Caenorhabditis elegans oocyte maturation determinant OMA
      1.
AB  - Maternally supplied mRNAs encode proteins that pattern early embryos in many
      species. In the nematode Caenorhabditis elegans, a suite of RNA-binding proteins
      regulates expression of maternal mRNAs during oogenesis, the oocyte to embryo
      transition, and early embryogenesis. To understand how these RNA-binding proteins
      contribute to development, it is necessary to determine how they select specific
      mRNA targets for regulation. OMA-1 and OMA-2 are redundant proteins required for
      oocyte maturation--an essential part of meiosis that prepares oocytes for
      fertilization. Both proteins have CCCH type tandem zinc finger RNA-binding
      domains. Here, we define the RNA binding specificity of OMA-1 and demonstrate
      that OMA-1/2 are required to repress the expression of a glp-1 3'-UTR reporter in
      developing oocytes. OMA-1 binds with high affinity to a conserved region of the
      glp-1 3'-UTR previously shown to interact with POS-1 and GLD-1, RNA-binding
      proteins required for glp-1 reporter repression in the posterior of fertilized
      embryos. Our results reveal that OMA-1 is a sequence-specific RNA-binding protein
      required to repress expression of maternal transcripts during oogenesis and
      suggest that interplay between OMA-1 and other factors for overlapping binding
      sites helps to coordinate the transition from oocyte to embryo.

PMID- 24014034
TI  - Dual positive feedback regulation of protein degradation of an extra-cytoplasmic
      function sigma factor for cell differentiation in Streptomyces coelicolor.
AB  - Here we report that in Streptomyces coelicolor, the protein stability of an ECF
      sigma factor SigT, which is involved in the negative regulation of cell
      differentiation, was completely dependent on its cognate anti-sigma factor RstA.
      The degradation of RstA caused a ClpP/SsrA-dependent degradation of SigT during
      cell differentiation. This was consistent with the delayed morphological
      development or secondary metabolism in the DeltaclpP background after rstA
      deletion or sigT overexpression. Meanwhile, SigT negatively regulated clpP/ssrA
      expression by directly binding to the clpP promoter (clpPp). The SigT-clpPp
      interaction could be disrupted by secondary metabolites, giving rise to the
      stabilized SigT protein and retarded morphological development in a non
      antibiotic-producing mutant. Thus a novel regulatory mechanism was revealed that
      the protein degradation of the ECF sigma factor was initiated by the degradation
      of its anti-sigma factor, and was accelerated in a dual positive feedback manner,
      through regulation by secondary metabolites, to promote rapid and irreversible
      development of the secondary metabolism. This ingenious cooperation of
      intracellular components can ensure economical and exquisite control of the ECF
      sigma factor protein level for the proper cell differentiation in Streptomyces. 

PMID- 24014035
TI  - Mitochondrially mediated integrin alphaIIbbeta3 protein inactivation limits
      thrombus growth.
AB  - When platelets are strongly stimulated, a procoagulant platelet subpopulation is
      formed that is characterized by phosphatidylserine (PS) exposure and epitope
      modulation of integrin alphaIIbbeta3 or a loss of binding of activation-dependent
      antibodies. Mitochondrial permeability transition pore (mPTP) formation, which is
      essential for the formation of procoagulant platelets, is impaired in the absence
      of cyclophilin D (CypD). Here we investigate the mechanisms responsible for these
      procoagulant platelet-associated changes in integrin alphaIIbbeta3 and the
      physiologic role of procoagulant platelet formation in the regulation of platelet
      aggregation. Among strongly stimulated adherent platelets, integrin alphaIIbbeta3
      epitope changes, mPTP formation, PS exposure, and platelet rounding were closely
      associated. Furthermore, platelet mPTP formation resulted in a decreased ability
      to recruit additional platelets. In the absence of CypD, integrin alphaIIbbeta3
      function was accentuated in both static and flow conditions, and, in vivo, a
      prothrombotic phenotype occurred in mice with a platelet-specific deficiency of
      CypD. CypD-dependent proteolytic events, including cleavage of the integrin beta3
      cytoplasmic domain, coincided closely with integrin alphaIIbbeta3 inactivation.
      Calpain inhibition blocked integrin beta3 cleavage and inactivation but not mPTP
      formation or PS exposure, indicating that integrin inactivation and PS exposure
      are mediated by distinct pathways subsequent to mPTP formation. mPTP-dependent
      alkalinization occurred in procoagulant platelets, suggesting a possible
      alternative mechanism for enhancement of calpain activity in procoagulant
      platelets. Together, these results indicate that, in strongly stimulated
      platelets, mPTP formation initiates the calpain-dependent cleavage of integrin
      beta3 and associated regulatory proteins, resulting in integrin alphaIIbbeta3
      inactivation, and demonstrate a novel CypD-dependent negative feedback mechanism
      that limits platelet aggregation and thrombotic occlusion. 

PMID- 24014037
TI  - [Updated incidence of dry eye syndrome in Germany].
AB  - BACKGROUND: Dry eye is one of the most common eye surface disorders. Patients
      suffer in particular from annoying subjective symptoms that compromise quality of
      life. The aim of the study was to find out when patients consult ophthalmologists
      in Germany and what symptoms they present. PATIENTS/MATERIAL AND METHODS: 170
      patients treated at ophthalmological practices in Bavaria, Saxony and Saxony
      Anhalt with dry eye were surveyed regarding their symptoms. RESULTS: The majority
      of those questioned were 40 years of age or older (88 %) (average: 60), female
      (59 %) and described a variety of subjective symptoms (65 %). More than five
      different concurrent symptoms were named. There is a recognisable increase in
      cases - by more than 3.5 times - at the age of forty (in women) and fifty (in
      men). CONCLUSIONS: We hope to contribute with the data obtained to a more
      complete understanding of this highly complex pathological process. A further aim
      is to facilitate recognition of this mostly chronic condition in its early stages
      when the symptoms are still poorly defined. The data on the German population
      obtained here should become part of a comparative analysis within the
      international context. Despite considerable scientific effort, dry eye remains a
      difficult challenge for both patients and attending physicians.

PMID- 24014036
TI  - Glucose-starved cells do not engage in prosurvival autophagy.
AB  - In response to nutrient shortage or organelle damage, cells undergo
      macroautophagy. Starvation of glucose, an essential nutrient, is thought to
      promote autophagy in mammalian cells. We thus aimed to determine the role of
      autophagy in cell death induced by glucose deprivation. Glucose withdrawal
      induces cell death that can occur by apoptosis (in Bax, Bak-deficient mouse
      embryonic fibroblasts or HeLa cells) or by necrosis (in Rh4 rhabdomyosarcoma
      cells). Inhibition of autophagy by chemical or genetic means by using 3
      methyladenine, chloroquine, a dominant negative form of ATG4B or silencing Beclin
      1, Atg7, or p62 indicated that macroautophagy does not protect cells undergoing
      necrosis or apoptosis upon glucose deprivation. Moreover, glucose deprivation did
      not induce autophagic flux in any of the four cell lines analyzed, even though
      mTOR was inhibited. Indeed, glucose deprivation inhibited basal autophagic flux.
      In contrast, the glycolytic inhibitor 2-deoxyglucose induced prosurvival
      autophagy. Further analyses indicated that in the absence of glucose, autophagic
      flux induced by other stimuli is inhibited. These data suggest that the role of
      autophagy in response to nutrient starvation should be reconsidered. 

PMID- 24014038
TI  - [Charles Bonnet's syndrome: clinical insights in a fascinating disease].
AB  - Even mentally and cognitively healthy people can experience visual
      hallucinations. These are called Charles Bonnet's syndrome, named after the Swiss
      scientist, who first described such perceptions in the 18th century. Usually
      patients possess insight in the unreality of their visual experiences. The
      definitions of CBS are not consistent. Visual impairment or blindness is not part
      of every definition, but often is associated with CBS. Ophthalmologists should be
      aware of this syndrome, since its prevalence is high among blind or visually
      impaired people: patients often are reluctant to admit their hallucinatory
      experiences, because of the fear of being stigmatised. Possibly women are
      affected more often than men. CBS is well investigated in the elderly, but also
      young people might experience visual hallucinations. Hallucinatory contents
      commonly are persons, with varying duration of the hallucinations. Most patients
      experience more than one hallucinatory episode. CBS is best investigated in
      patients suffering from AMD. Neuroimaging studies suggest that cerebral
      abnormalities, mainly in the occipital cortex, might also play a role in the
      pathogenesis of CBS. Many patients do not require (drug) treatment, since
      education itself is helpful in most cases. The pathophysiology remains unclear,
      but there are a couple of theories. 

PMID- 24014039
TI  - Novel intra-adrenal secondary lymphoid follicle formation.

PMID- 24014041
TI  - Intravascular large B cell lymphoma presenting as a thyroid mass.

PMID- 24014040
TI  - Predictive factors of malignancy in thyroid nodules with a cytological diagnosis
      of follicular neoplasm.
AB  - In cases of follicular neoplasm identified by thyroid fine-needle aspiration
      (FNA), surgery is required to achieve a precise diagnosis. We investigated
      potential clinical factors for the preoperative prediction of malignancy in
      thyroid nodules with a cytological diagnosis of follicular neoplasm. We
      retrospectively reviewed the data of 97 patients who were diagnosed with
      follicular neoplasm by FNA and had undergone surgery at the Korea Cancer Center
      Hospital between April 2010 and April 2012. Age, sex, laboratory data (such as
      thyroid-stimulating hormone, free T4, thyroglobulin (Tg), and Tg antibody), and
      ultrasonographic findings were reviewed from the electronic medical records. Of
      97 patients, 50 (51.5 %) were diagnosed with benign nodules, 16 (16.5 %) with
      follicular thyroid carcinoma (FTC), and 31 (32.0 %) with papillary thyroid
      carcinoma (PTC). In comparison with the features of benign nodules, FTC presented
      with a large nodule size, high serum Tg level, isoechogenicity, calcifications,
      and peripheral halo, whereas PTC exhibited traits similar to those of benign
      nodules, except for high serum Tg level and the presence of calcifications on
      ultrasonography. Therefore, a high serum Tg level (>=75 ng/mL) and calcification
      were the only significant predictive factors for malignancy in case of follicular
      neoplasm (p < 0.01). Serum Tg levels and the presence of calcification on
      ultrasonography are important clinical features to predict malignancy in thyroid
      nodules with cytological diagnosis of follicular neoplasm. 

PMID- 24014042
TI  - Therapeutic alliance in two treatments for adults with severe and enduring
      anorexia nervosa.
AB  - OBJECTIVE: The aim of this study was to investigate the strength and role of
      therapeutic alliance in a trial comparing Cognitive Behavioral Therapy for
      anorexia nervosa (CBT-AN) and Specialist Supportive Clinical Management for the
      treatment of severe and enduring AN (SE-AN). METHOD: Participants were 63 adult
      females with SE-AN presenting to an outpatient, multisite randomized controlled
      trial conducted at two clinical sites. Participants completed measures assessing
      their perception of the quality of the therapeutic relationship, eating disorder
      (ED) symptomatology, and depressive symptomatology. RESULTS: Beyond the effect of
      early treatment change and treatment assignment, early therapeutic alliance was a
      significant predictor of Restraint and Shape Concern at follow-up (ps < .02).
      Late therapeutic alliance was a significant predictor of weight change,
      depressive symptomatology, and ED symptomatology at end of treatment and follow
      up (ps < .008), with the exception of Shape Concern at follow-up (p = .07).
      DISCUSSION: The results suggest that therapeutic alliance can be effectively
      established in the treatment of SE-AN and may be relevant for treatment response,
      particularly in late treatment, on some aspects of ED and depressive
      symptomatology.

PMID- 24014044
TI  - Selective reduction of amides to amines by boronic acid catalyzed
      hydrosilylation.
AB  - Not a 'B'ore! Benzothiophene-based boronic acids catalyze the reduction of
      tertiary, secondary, and primary amides in the presence of a hydrosilane. The
      reaction demonstrates good functional-group tolerance. 

PMID- 24014043
TI  - Striatal parvalbuminergic neurons are lost in Huntington's disease: implications
      for dystonia.
AB  - Although dystonia represents a major source of motor disability in Huntington's
      disease (HD), its pathophysiology remains unknown. Because recent animal studies
      indicate that loss of parvalbuminergic (PARV+) striatal interneurons can cause
      dystonia, we investigated if loss of PARV+ striatal interneurons occurs during
      human HD progression, and thus might contribute to dystonia in HD. We used
      immunolabeling to detect PARV+ interneurons in fixed sections, and corrected for
      disease-related striatal atrophy by expressing PARV+ interneuron counts in ratio
      to interneurons co-containing somatostatin and neuropeptide Y (whose numbers are
      unaffected in HD). At all symptomatic HD grades, PARV+ interneurons were reduced
      to less than 26% of normal abundance in rostral caudate. In putamen rostral to
      the level of globus pallidus, loss of PARV+ interneurons was more gradual, not
      dropping off to less than 20% of control until grade 2. Loss of PARV+
      interneurons was even more gradual in motor putamen at globus pallidus levels,
      with no loss at grade 1, and steady grade-wise decline thereafter. A large
      decrease in striatal PARV+ interneurons, thus, occurs in HD with advancing
      disease grade, with regional variation in the loss per grade. Given the findings
      of animal studies and the grade-wise loss of PARV+ striatal interneurons in motor
      striatum in parallel with the grade-wise appearance and worsening of dystonia,
      our results raise the possibility that loss of PARV+ striatal interneurons is a
      contributor to dystonia in HD.

PMID- 24014045
TI  - Near-infrared spectroscopic evaluation of lyophilized viral vaccine formulations.
AB  - This article examines the applicability of near-infrared spectroscopy (NIRS) to
      evaluate the virus state in a freeze-dried live, attenuated vaccine formulation.
      Therefore, this formulation was freeze-dried using different virus volumes and
      after applying different pre-freeze-drying virus treatments (resulting in
      different virus states): (i) as used in the commercial formulation; (ii) without
      antigen (placebo); (iii) concentrated via a centrifugal filter device; and (iv)
      stressed by 96 h exposure to room temperature. Each freeze-dried product was
      measured directly after freeze-drying with NIR spectroscopy and the spectra were
      analyzed using principal component analysis (PCA). Herewith, two NIR spectral
      regions were evaluated: (i) the 7300-4000 cm(-1) region containing the amide A/II
      band which might reflect information on the coated proteins of freeze-dried live,
      attenuated viruses; and (ii) the C-H vibration overtone regions (10,000-7500 and
      6340-5500 cm(-1) ) which might supply information on the lipid layer surrounding
      the freeze-dried live, attenuated viruses. The different pre-freeze-drying
      treated live, attenuated virus formulations (different virus states and virus
      volumes) resulted in different clusters in the scores plots resulting from the
      PCA of the collected NIR spectra. Secondly, partial least squares discriminant
      analysis models (PLS-DA) were developed and evaluated, allowing classification of
      the freeze-dried formulations according to virus pretreatment. The results of
      this study suggest the applicability of NIR spectroscopy for evaluating live,
      attenuated vaccine formulations with respect to their virus pretreatment and
      virus volume.

PMID- 24014046
TI  - Di(imino)aryltin(IV) dichlorides as tectons for heterometallic coordination
      compounds.
AB  - Hydrolysis of [2-{(CH2O)2CH}C6H4]2SnCl2 (1) [prepared from 2-[(CH2O)2CH]C6H4MgBr
      and SnCl4, in 2 : 1 molar ratio] gave [2-(O=CH)C6H4]2SnCl2 (2). Treatment of with
      the appropriate amine, in the absence of a solvent or catalyst, resulted in the
      isolation in high yields of [2-(RN[double bond, length as m-dash]CH)C6H4]2SnCl2
      [R = 2'-C10H7 (3), 2',4',6'-Me3C6H2 (4), PhCH2 (5), Me2NCH2CH2 (6), 2'-PyCH2
      (7)]. The reaction of with [Pd(COD)Cl2] provided the heterometallic species
      [Cl2Pd{2-(2'-PyCH2N[double bond, length as m-dash]CH)C6H4}2SnCl2] (8). The
      compounds were characterised by multinuclear NMR spectroscopy in solution, and
      mass spectrometry and IR spectroscopy in the solid state. The molecular
      structures of 1, 2, 4-7 and 8.CH3CN were established by single-crystal X-ray
      diffraction. For all diorganotin(IV) dichlorides intramolecular O->Sn or Nimine
      >Sn coordination results in hypercoordinated species with a distorted octahedral
      (C,E)2SnCl2 core (E = O, N). The presence of intramolecular N->Sn interactions in
      solution, responsible for the restriction of free rotation of mesityl groups
      around the C-N(=C) single bonds, is suggested by (1)H and (13)C NMR data. In the
      heterometallic dinuclear complex 8 the octahedral coordination around tin is
      preserved as in 7 and the nitrogen atoms from the pyridyl groups in the pendant
      arms are coordinated to palladium, leading to a trans-square planar PdCl2N2 core.

PMID- 24014047
TI  - Semiquantitative classification of ductus venosus blood flow patterns.
AB  - OBJECTIVES: To identify the range of waveform abnormalities in the ductus venosus
      (DV) characterized by their timing in the cardiac cycle and to evaluate if they
      can be categorized into distinct patterns. METHODS: DV velocity ratios were
      calculated from peak velocities during ventricular systole (S), end-systolic
      ventricular relaxation (v), early diastole (D) and atrial systole (a) (S/v, S/D,
      v/D, S/a, v/a and D/a ratios). The ratios were converted to their Z-scores and
      elevation > 2 SD was assigned as abnormal. Combinations of ratio abnormalities
      were grouped to define distinct waveform patterns and their distribution was
      related to the clinical presentation. RESULTS: Five-hundred and forty-two
      abnormal DV waveforms fell into three principal patterns. In Pattern 1 only the a
      wave-related ratios were abnormal (180, 33.2%), in Pattern 2 the v/D ratio was
      abnormal (143, 26.3%) and in Pattern 3 combinations of a-wave abnormalities in
      the presence of a normal v/D ratio were normal (94, 17.3%). CONCLUSIONS:
      Interpretation of venous waveform patterns is complex because the multiphasic
      waveforms reflect events in the cardiac cycle that may be differentially affected
      by clinical pathology. We sought to present a classification for the DV flow
      profile that characterizes abnormal flow confined to atrial systole and occurs
      during ventricular relaxation or during holodiastole. Further research is
      warranted to determine the significance of these patterns in specific fetal
      conditions.

PMID- 24014048
TI  - Epitope analysis and detection of human chorionic gonadotropin (hCG) variants by
      monoclonal antibodies and mass spectrometry.
AB  - Human chorionic gonadotropin (hCG) is an important marker for pregnancy,
      pregnancy-related disorders, and various cancers. Different molecular forms of
      hCG occur in different clinical conditions, and these can be distinguished with
      immunoassays using well-characterized monoclonal antibodies. Exact knowledge of
      the epitopes of the antibodies used is crucial for the design of assays with
      desired specificity. The epitopes of many hCG antibodies have been determined by
      comparing their reactivity with six 1st International Reference Reagents (IRRs)
      for hCG, but the specificity of some antibodies remains to be exactly defined. We
      have therefore studied the reactivity of 30 monoclonal antibodies (mAbs) with the
      six 1st IRRs for hCG, and variants were investigated using immunoaffinity
      extraction combined with liquid chromatography-mass spectrometry (LC-MS/MS) for
      the detection of hCG variants by specific tryptic signature peptides. Each of the
      mAbs had previously been characterized with regard to epitope specificity in the
      2nd Tissue Differentiation Workshop on hCG of the International Society of
      Oncology and BioMarkers (ISOBM). Simultaneous identification of different hCG
      variants by LC-MS/MS confirmed that two standards used for mAb characterization,
      nicked hCG (hCGn, 1st IRR 99/642) and nicked beta subunit of hCG (hCGbetan, 1st
      IRR 99/692), are heterogeneous, being composed of two major variants each:
      hCGn44/45 and hCGn47/48 as well as hCGbetan44/45 and hCGbeta47/48. Furthermore,
      MS revealed cross-contamination by non-nicked hCG of the 1st IRR hCGn (99/642)
      standard. This information enabled fine-tuning of the previous epitope
      classifications of mAbs specific for heterodimeric hCG (c-mAbs). LC-MS/MS
      confirmed that c2-mAbs and most c1-mAbs did not recognize hCGn as the observed
      response in radioimmunoassays obviously resulted from the contamination of hCGn
      with hCG. Thus, c1 and c2 epitopes are partially dependent on hCGbeta peptide
      loop 2. c3-mAbs recognized both hCG and hCGn. It appeared that c-mAbs cannot
      discriminate between hCGn44/45 and hCGn47/48 as they either recognize both or
      neither variant. For most mAbs directed against hCGbeta, epitope specificity
      determined by LC-MS/MS was highly concordant with that obtained using standard
      immunological methods. In analogy to c-mAbs, hCGbeta-mAbs cannot discern between
      hCGbetan44/45, hCGbetan47/48, or intact hCGbeta as all 15 mAbs recognizing
      hCGbeta also recognized both nicked variants irrespective of which of the three
      major hCGbeta antigenic domains their epitopes were located within: on the caps
      of peptide loops 1 and 3, around the cystine knot, or along the hCGbetaCTP. LC
      MS/MS confirmed that their epitopes were not located on hCGbeta peptide loop 2.
      Thus, LC-MS/MS provided in-depth information on hCG variant composition of hCGn
      (99/642) and hCGbetan (99/692) and hCG variant specificity profiles and
      facilitated precise classification of the epitopes of anti-hCG mAbs. This has
      impact on the design of selective immunoassays.

PMID- 24014049
TI  - Association of COX2 gene hypomethylation with intestinal type gastric cancer in
      samples of patients from northern Brazil.
AB  - To verify the methylation status of THBS1, GPX3, and COX2 genes and to evaluate
      their association with Helicobacter pylori in gastric adenocarcinomas.
      Methylation-sensitive restriction enzyme PCR assay was performed in 16 diffuse
      type gastric cancer samples, 23 intestinal type, and 15 normal stomach tissue.
      The presence of H. pylori was performed by amplification of the fragment of the
      16S rRNA. Statistical analyses were performed using Fisher's exact test. The
      hypermethylation of GPX3, THBS1, and COX2 occurred in 18 (n = 7), 5 (n = 2), and
      36 % (n = 14) of gastric cancer samples, respectively, whereas in normal samples,
      it was found in 13, 7, and 67 %. The presence of H. pylori was detected in 67 %
      of gastric cancer samples and 67 % in normal gastric samples. The methylation of
      THBS1 and GPX3 was not significantly different between the types of tumors,
      normal sample, the presence of H. pylori, or clinicopathological variables
      studied (P > 0.05). However, the methylation status of the gene COX2 is
      significantly different between normal tissue and intestinal type gastric cancer
      (P = 0.02). Therefore, our results suggest that the methylation status of the
      gene COX2 is associated with the intestinal type of gastric cancer.

PMID- 24014050
TI  - The role of Bax and Bcl-2 in gemcitabine-mediated cytotoxicity in uveal melanoma
      cells.
AB  - Gemcitabine (GEM), a new cytotoxic agent, was shown to be effective against uveal
      melanoma (UM) which is noted for its resistance to chemotherapy. In this study,
      we found the different sensitivities to GEM in UM cell lines and identified
      apoptotic cell death as the cause of GEM cytotoxicity. Both UM cell lines showed
      an increase in Bax protein levels and activation of cleaved Caspase 3.
      Additionally, SP6.5 cells showed a gradual increase in Bcl-2 expression over
      time, whereas VUP cells showed almost none. After interfering in the expression
      of Bcl-2, the sensitivity to GEM was obviously enhanced in SP6.5 cells. These
      results suggest that an increase in Bax plays a crucial role in apoptotic cell
      death induced by GEM in the absence of p53. Moreover, inhibition of Bcl-2
      expression can efficiently enhance the cytotoxic effect of, and sensitivity to,
      GEM in UM cells.

PMID- 24014051
TI  - Role of dysregulated expression of leptin and leptin receptors in colorectal
      carcinogenesis.
AB  - Leptin is a multifunctional adipose-derived cytokine that plays a critical role
      in bodyweight homeostasis and energy balance. Plasma level of leptin is an
      indicator of the amount of energy stored in adipose tissues. Recently, leptin and
      leptin receptor dysregulation have been reported in a variety of malignant cells
      including colorectal cancers (CRCs). There are growing evidence that leptin may
      be the link between obesity and CRC carcinogenesis. Leptin influence the growth
      and proliferation of cancer cells via activation of various growth and survival
      signaling pathways including JAK/STAT, PI3-kinase/AKT, and/or MAP kinases. In
      this review, current understanding of leptin and its receptor's roles in the
      pathogenesis of colonogenic cancer has been described.

PMID- 24014052
TI  - The prognostic value of elevated ezrin in patients with osteosarcoma.
AB  - Published studies researching the prognostic significance of ezrin expression in
      patients with osteosarcoma are inconclusive and heterogeneous. We conducted a
      meta-analysis to assess its prognostic value more precisely. The hazard ratios
      with corresponding 95 % confidence intervals were calculated to evaluate the
      effects. Five studies with 318 osteosarcoma patients were included to estimate
      the relationship between ezrin and disease-free survival, and ezrin and overall
      survival. Compared with osteosarcoma patients with low or negative ezrin
      expression, patients with high ezrin expression tended to be associated with
      lower disease-free survival, but the difference was not significant. However,
      patients with high ezrin expression were obviously associated with lower overall
      survival. Therefore, the findings from this systematic review suggest that ezrin
      expression is an effective biomarker of prognosis in patients with osteosarcoma.

PMID- 24014053
TI  - A systematic review of p53 as a biomarker of survival in patients with
      osteosarcoma.
AB  - Osteosarcoma is the most common malignant bone tumor, and the prognosis of
      patients with osteosarcoma is still unsatisfactory with low survival rates. There
      are many studies assessing the prognostic role of upregulated p53 in patients
      presenting osteosarcoma, and there is no consistent finding. To summarize the
      existing evidence about whether the presence of upregulated p53 was a biomarker
      of survival in patients with osteosarcoma, we performed a systematic review and
      meta-analysis of relevant publications. We assessed the effect of upregulated p53
      on the 3-year overall survival and the 3-year disease-free survival by
      calculating the pooled odds ratio (OR) with corresponding 95% confidence interval
      (95%CI). Fifteen studies with a total of 609 patients with osteosarcoma were
      finally included into the systematic review and meta-analysis. Compared with
      osteosarcoma patients with low or undetectable p53, patients with upregulated p53
      were obviously associated with decreased 3-year overall survival (OR = 0.29, 95
      %CI 0.19-0.43, P < 0.001). In addition, patients with upregulated p53 were
      obviously associated with decreased 3-year disease-free survival (OR = 0.06, 95
      %CI 0.02-0.23, P < 0.001). The results from the systematic review and meta
      analysis highlight that p53 is an effective biomarker of survival in patients
      with osteosarcoma. In addition, more studies with a large sample size are needed
      to identify the effect of p53 expression in osteosarcoma patients.

PMID- 24014054
TI  - Self-assembled supramolecular channels: toward biomimetic materials for
      directional translocation.
AB  - This Personal Account summarizes the recent developments in the development of
      self-assembled supramolecular channels and their dimensional extension towards up
      scaled self-organized materials. This Personal Account begins with a short, non
      exhaustive description of artificial supramolecular channel systems that are
      involved in water-, proton-, and ion-transport processes through bilayer
      membranes. Then, these "all-made" artificial systems will be described as a
      source of inspiration, by presenting several breakthroughs over the last few
      years in the field of biomimetic supramolecular channel systems. Their inclusion
      in artificial polymeric/hybrid matrixes, which results in the formation of
      biomimetic artificial materials for directional translocation through channeling
      pathways, will be described in the last part of the Personal Account, with an
      emphasis on all of the efforts that are necessary to maintain their channel
      transporting function within bilayer membranes under up-scaled operating
      conditions. 

PMID- 24014055
TI  - A panoramic view of the skull base: systematic review of open and endoscopic
      endonasal approaches to four tumors.
AB  - Endoscopic endonasal surgery has been established as the safest approach to
      pituitary tumors, yet its role in other common skull base lesions has not been
      established. To answer this question, we carried out a systematic review of
      reported series of open and endoscopic endonasal approaches to four major skull
      base tumors: olfactory groove meningiomas (OGM), tuberculum sellae meningiomas
      (TSM), craniopharyngiomas (CRA), and clival chordomas (CHO). Data from 162
      studies containing 5,701 patients were combined and compared for differences in
      perioperative mortality, gross total resection (GTR), cerebrospinal fluid (CSF)
      leak, neurological morbidity, post-operative visual function, post-operative
      anosmia, post-operative diabetes insipidus (DI), and post-operative
      obesity/hyperphagia. Weighted average rates for each outcome were calculated
      using relative study size. Our findings indicate similar rates of GTR and
      perioperative mortality between open and endoscopic approaches for all tumor
      types. CSF leak was increased after endoscopic surgery. Visual function symptoms
      were more likely to improve after endoscopic surgery for TSM, CRA, and CHO. Post
      operative DI and obesity/hyperphagia were significantly increased after open
      resection in CRA. Recurrence rates per 1,000 patient-years of follow-up were
      higher in endoscopy for OGM, TSM, and CHO. Trends for open and endoscopic surgery
      suggested modest improvement in all outcomes over time. Our observations suggest
      that endonasal endoscopy is a safe alternative to craniotomy and may be preferred
      for certain tumor types. However, endoscopic surgery is associated with higher
      rates of CSF leak, and possibly increased recurrence rates. Prospective study
      with long-term follow-up is required to verify these preliminary observations. 

PMID- 24014056
TI  - Telehealth cognitive behavior therapy for co-occurring insomnia and depression
      symptoms in older adults.
AB  - OBJECTIVE: Telehealth has proven effective with a wide range of disorders, but
      there is a paucity of data on the use of telehealth using cognitive-behavior
      therapy (CBT) with late-life insomnia and depression. This pilot study was
      designed to examine the feasibility and effectiveness of using telehealth to
      treat older adults with comorbid insomnia and depression living in rural Alabama.
      METHOD: Five patients received 10 sessions of CBT for insomnia and depression.
      Patients were engaged in treatment via Skype from their primary care physician's
      office. Assessments were conducted at baseline, posttreatment, and 2-month follow
      up. RESULTS: Patients exhibited clinically significant improvement in both
      insomnia (sleep diaries and Insomnia Severity Index) and depression (Hamilton
      Rating Scale for Depression) at posttreatment, and these gains were well
      maintained at 2-month follow-up. CONCLUSIONS: These preliminary data suggest that
      telehealth may be an effective means of providing treatment to older adults,
      including underserved populations.

PMID- 24014057
TI  - A randomized controlled trial of an internet intervention for adults with
      insomnia: effects on comorbid psychological and fatigue symptoms.
AB  - OBJECTIVE: Insomnia is frequently comorbid with other medical and psychological
      disorders. This secondary data analysis investigated whether an Internet
      delivered cognitive behavioral therapy for insomnia (CBT-I) intervention could
      also reduce comorbid psychological and fatigue symptoms. METHOD: Data from a
      pilot randomized controlled trial (RCT) testing the efficacy of Internet
      delivered CBT-I relative to a waitlist control was used to examine changes in
      symptoms of depression, anxiety, mental health quality of life (QOL), and
      fatigue. RESULTS: Group by time interactions from repeated measures analyses
      revealed significant post intervention improvements in Internet participants (n =
      22) relative to control participants (n = 22) on all psychological symptoms,
      mental health QOL, and fatigue. A small post hoc subsample of Internet
      participants with mild or moderate depression also showed large effect size
      changes in these constructs (depression, anxiety, mental health QOL, and
      fatigue). CONCLUSION: Internet-delivered CBT-I appears to not only improve sleep
      but also reduce comorbid psychological and fatigue symptoms.

PMID- 24014058
TI  - Type and branched pattern of N-glycans and their structural effect on the chicken
      egg allergen ovotransferrin: a comparison with ovomucoid.
AB  - Ovotransferrin (OT), a multifunctional glycoprotein with defensive and protective
      activities, accounts for approximately 13% of chicken egg white proteins and is
      known as a major egg-associated allergen along with ovomucoid (OM). In contrast
      to the well-characterized N-glycans of OM, the N-glycan structure of OT has not
      been reported. Here, using HPLC equipped with a fluorescence detector and mass
      spectrometric analysis in combination with exoglycosidase digestion, we
      investigated the N-glycan type and branched pattern of OT, and compared them with
      those of OM. The HPLC peak area was used to calculate the relative quantity (%)
      of each glycan. Seventeen N-glycans, including 11 glycans (1 core structure and
      10 complex-type oligosaccharides), that commonly exist in ovotransferrin and
      ovomucoid were identified. Six characteristic glycans (2 truncated structures, 1
      complex-type, and 3 hybrid-type oligosaccharides) in OT and eight characteristic
      glycans in OM were classified. OT contains the following branched complex-type
      structures: mono-(13.2%), bi-(23.9%), tri-(9.0%), tetra-(2.7%), and penta-(2.8%)
      antennary oligosaccharides. However, OM contained mostly tri-(33.5%) and penta
      (31.2%) antennary oligosaccharides. The N-glycan-containing bisecting N
      acetylglucosamine comprised 43.4% and 79.8% of the total glycans in OT and OM,
      respectively. Moreover, using circular dichroism analysis, we observed that the
      secondary structure of the deglycosylated OT is quite different from that of the
      intact protein. To our knowledge, this is the first study to analyze N-glycans in
      OT in comparison with those of OM.

PMID- 24014066
TI  - Single institutional experience of the treatment of angiosarcoma of the face and
      scalp.
AB  - OBJECTIVE: Angiosarcoma is a rare malignant neoplasm with a poor prognosis. A
      retrospective study was performed to accumulate radiotherapy (RT) data. METHODS:
      Data from 17 patients with angiosarcoma of the face and scalp (AFS) who were
      treated with definitive RT between January 1999 and July 2011 were
      retrospectively analysed. The total radiation dose was 70 Gy, and the fractional
      doses were 2.0-2.5 Gy. Combined with RT, chemotherapy using docetaxel alone,
      recombinant interleukin-2 immunotherapy alone and both of these was performed in
      10, 4 and 2 patients, respectively. Three patients underwent limited surgery
      before RT. RESULTS: The response rate was 82%, and the median overall survival
      (OS) rate was 26 months. Locoregional relapse alone, distant metastasis alone and
      both of these were confirmed in 4, 5 and 4 patients, respectively. Patients
      treated with docetaxel showed a better prognosis (p=0.0477), a distant metastasis
      free rate (p=0.0063) and a better in-field control rate, although the last was
      not statistically significant (p=0.1645). CONCLUSION: Definitive RT combined with
      docetaxel chemotherapy provided an effective approach for treating AFS. ADVANCES
      IN KNOWLEDGE: Since patients treated with chemoradiotherpy using docetaxel showed
      better OS and distant metastasis-free rates than those who did not receive
      docetaxel, it was warranted to continue use of docetaxel. In chemoradiotherapy at
      a dose of 70 Gy using docetaxel, 2-year in-field control rate was 67%.

PMID- 24014068
TI  - Context matters in pediatric obesity: commentary on innovative treatment and
      prevention programs for pediatric overweight and obesity.
AB  - This commentary reviews the 9 articles in the Special Issue on Innovative
      Treatment and Prevention Programs for Pediatric Overweight and Obesity. Taking a
      socio-ecological perspective, contextual factors such as characteristics of the
      child, family, community, and culture are offered as ways to improve treatment
      and prevention programs. Using a more tailored approach that takes into account
      individual differences in family communication patterns and problem solving is
      warranted. Pediatric psychologists are urged to consider the role of prevention
      and targeted efforts during early childhood to reduce the prevalence of childhood
      obesity.

PMID- 24014067
TI  - Affect and eating behavior in obese adults with and without elevated depression
      symptoms.
AB  - OBJECTIVE: Although there is a modest relation between obesity and depression,
      mechanisms that contribute to this co-occurrence are unclear. This study examined
      mood and eating behavior among obese adults with and without elevated depression
      symptoms. METHOD: Obese adults (N = 50) were subtyped according to a Beck
      Depression Inventory (BDI) cutoff of 14, indicating "probable depression."
      Participants with (BDI >= 14; n = 15) and without (BDI < 14; n = 35) elevated
      depression symptoms were compared on affect- and eating-related variables
      measured via questionnaire and ecological momentary assessment (EMA) using ANCOVA
      and mixed model regression. RESULTS: After adjusting for group differences in
      body mass index (BMI; p = .03), participants with elevated depression symptoms
      reported greater emotional eating via self-report questionnaire [F(1,50) = 4.3; p
      = .04], as well as more frequent binge eating (Wald chi(2)  = 13.8; p < .001) and
      higher daily negative affect (Wald chi(2)  = 7.7; p = .005) on EMA recordings.
      Emotional eating mediated the relationship between depression status and BMI
      (indirect effect estimate = 3.79; 95% CI = 1.02-7.46). DISCUSSION: Emotional
      eating and binge eating were more commonly reported by obese adults with elevated
      depression symptoms compared to those without and may occur against a general
      backdrop of overall low mood. Intervention and prevention programs for obesity
      and/or depression should address disordered eating to prevent or minimize adverse
      health consequences.

PMID- 24014069
TI  - Investigating the effect of peptide agonists on the chondrogenic differentiation
      of human mesenchymal stem cells using design of experiments.
AB  - Human mesenchymal stem cells (MSCs) are attractive for use in cartilage tissue
      engineering. Cells are often seeded in a structural scaffold containing growth
      factors. Peptide mimics of full-length growth factors are a promising alternative
      because they are less expensive and easier to manufacture. We investigated four
      short peptides for their effect on the chondrogenesis of human MSCs. The peptides
      were originally designed to mimic bone morphogenetic protein-2 (BMP-2),
      transforming growth factor-beta 1 (TGF-beta1), and insulin, all of which have
      been shown to affect MSC chondrogenesis. Previous studies demonstrated that the
      peptides elicited bioactivity in other cell types, but the peptides have not been
      investigated for their effect on chondrogenesis in human MSCs. In a preliminary
      investigation, peptides were added to a pellet culture of human MSCs and assayed
      for their effect on glycosaminoglycan (GAG) production. These experiments
      determined peptide concentrations used in a full-factorial experiment to
      investigate any interactions. The experiment revealed the BMP peptide as a robust
      stimulant for GAG production. .

PMID- 24014070
TI  - Emerging issues on comprehensive hemophilia care: preventing, identifying, and
      monitoring age-related comorbidities.
AB  - Life expectancy for persons with hemophilia (PWH) has considerably increased in
      the last decades as a direct result of the availability of modern therapies to
      control the clotting defect. Because their life expectancy now matches that of
      the general population, PWH are experiencing age-related comorbidities, such as,
      cardiovascular diseases, metabolic syndrome, renal diseases, sexuality issues,
      malignancies, and neurologic problems, that until recently have been rarely seen
      in this group of patients. In this article, we present a summary of the current
      knowledge on the aging PWH along with the clinical approaches that may be
      integrated into the routine comprehensive care of these patients for preventing,
      diagnosing, and monitoring age-related comorbidities. In general, patients with
      and without hemophilia should receive similar care, with close collaboration
      between the physician treating PWH and the specialty expert treating the comorbid
      disease. 

PMID- 24014071
TI  - FEIBA versus NovoSeven in hemophilia patients with inhibitors.
AB  - The management of patients with congenital hemophilia who develop alloantibodies
      that neutralize coagulation factor activity is the most important challenge for
      hemophilia care providers because this complication renders replacement treatment
      with factor concentrates partially or completely ineffective, exposing the
      patients to an increased risk of morbidity and mortality. Development of
      inhibitors complicates the clinical course of severe hemophilia in up to 30% of
      patients with hemophilia A and up to 5% of those with hemophilia B. Although the
      ultimate goal of treatment of patients with alloantibodies against factors VIII
      and IX is eradication of the inhibitor, the control of bleeding through high
      doses of factor concentrates (low titer inhibitors) or bypassing agents (high
      titer inhibitors) is the mainstay of management of these patients. In this
      review, we summarize the main characteristics of the bypassing agents FEIBA and
      NovoSeven, briefly discussing available literature data, and in particular,
      focusing on comparative studies. 

PMID- 24014072
TI  - Identifying nongenetic risk factors for inhibitor development in severe
      hemophilia a.
AB  - The development of inhibitory antibodies against infused factor VIII (FVIII) is a
      major challenge in hemophilia treatment. As the antibodies swiftly inactivate
      administered therapeutic FVIII concentrates, FVIII is no longer effective in
      controlling bleeding. To achieve adequate hemostasis, bypassing therapies are
      required, with accompanying clinical challenges and financial expense. Extensive
      research has aimed to elucidate the multifactorial etiology of inhibitor
      development. Both genetic and nongenetic causes have been identified.
      Identification of treatment-related risk factors would offer the possibility to
      modify treatment strategies in high-risk patients, thereby reducing the risk of
      inhibitor development. Have we presently gained sufficient knowledge to make a
      prediction of the inhibitor risk possible and justify changes in treatment
      regimens for specific patient groups? This review summarizes and evaluates the
      research findings on nongenetic risk factors of inhibitor development, with
      special focus on treatment-related factors. 

PMID- 24014073
TI  - Hemophilia a and hemophilia B: different types of diseases?
AB  - Hemophilia A and B are traditionally considered clinically indistinguishable;
      however, differences in bleeding frequency, clinical scores, use of prophylaxis,
      and need for orthopedic surgery have been reported, suggesting that the bleeding
      tendency associated with factor IX deficiency may be less severe with consequent
      better outcomes in the long term.Hemophilia A and B show their own peculiar
      aspects, not only in terms of epidemiological and clinical features, including
      inhibitor incidence and associated symptoms, but also with respect to molecular
      defects. The type of factor VIII/IX mutation is a major determinant of the
      bleeding tendency as well as of the risk of inhibitor formation; thus, there is a
      biological plausibility behind the different clinical expression of these two
      forms of congenital hemophilia. The distinction of various bleeding phenotypes in
      hemophilia has considerable therapeutic implications; therefore, further research
      in this field is required to optimize treatment regimens. 

PMID- 24014074
TI  - Rotigotine polyoxazoline conjugate SER-214 provides robust and sustained
      antiparkinsonian benefit.
AB  - Currently available dopaminergic drugs such as levodopa and dopamine (DA)
      receptor agonists impart considerable improvement in Parkinson's disease (PD)
      motor symptoms but often lead to significant motor complications including
      "wearing-off" and dyskinesia. Such complications are believed to stem from the
      pulsatile nature of dopaminergic stimulation with these agents. Continuous
      dopaminergic drug delivery using polyoxazoline (POZ) polymer conjugation may
      improve motor symptoms, while avoiding development of side effects. The purposes
      of the current study are to characterize the in vitro and in vivo
      pharmacokinetics of POZ conjugation of a U.S. Food and Drug Administration (FDA)
      approved DA agonist, rotigotine, and to evaluate their effects in an established
      rat model of PD. After determination of release profiles of several POZ
      conjugated constructs ("fast": SER-212; "moderate": SER-213; and "slow": SER-214)
      using in vitro hydrolysis, normal male Sprague-Dawley rats were used for
      determination of the pharmacokinetic profile of both acute and chronic exposure.
      Finally, a separate group of rats was rendered hemiparkinsonian using
      intracranial 6-hydroxydopamine (6-OHDA) infusions, treated acutely with POZ
      rotigotine, and assessed for rotational behavior and antiparkinsonian benefit
      using the cylinder test. POZ-rotigotine formulations SER-213 and SER-214 led to
      substantial pharmacokinetic improvement compared to unconjugated rotigotine. In
      addition, SER-214 led to antiparkinsonian effects in DA-lesioned rats that
      persisted up to 5 days posttreatment. Repeated weekly dose administration of SER
      214 to normal rats for up to 12 weeks demonstrated highly reproducible
      pharmacokinetic profiles. The continuous dopaminergic stimulation profile
      afforded by SER-214 could represent a significant advance in the treatment of PD,
      with potential to be a viable, once-per-week therapy for PD patients. 

PMID- 24014075
TI  - Transition readiness in adolescents and emerging adults with diabetes: the role
      of patient-provider communication.
AB  - Transition from pediatric to adult care represents a high risk period for
      adolescents and emerging adults with diabetes. Fundamental differences between
      pediatric and adult care delivery models may contribute to increased risk for
      poor health outcomes. This review provides a brief overview of models of care in
      pediatric and adult settings and focuses on patient-provider communication
      content and quality as potential points of intervention to improve transition
      related outcomes. This review also highlights disparities in transition and
      communication for adolescents and emerging adults from racial/ethnic minority
      groups and discusses recent changes in health care legislation that have
      significant implications for the transition process. Intervention opportunities
      include programs to enhance developmentally-appropriate patient-provider
      interactions and increased attention to promoting transition readiness skills.
      Improving patient-provider communication may hasten the development of vital self
      advocacy skills needed in adult health care systems and, thus, help establish a
      lasting pattern of positive diabetes self-care. 

PMID- 24014076
TI  - Adult and pediatric cases of B-cell lymphoblastic leukemia differ in the clinical
      significance of CD66c expression.

PMID- 24014077
TI  - Specificity of lipoxygenase pathways supports species delineation in the marine
      diatom genus Pseudo-nitzschia.
AB  - Oxylipins are low-molecular weight secondary metabolites derived from the
      incorporation of oxygen into the carbon chains of polyunsaturated fatty acids
      (PUFAs). Oxylipins are produced in many prokaryotic and eukaryotic lineages where
      they are involved in a broad spectrum of actions spanning from stress and defense
      responses, regulation of growth and development, signaling, and innate immunity.
      We explored the diversity in oxylipin patterns in the marine planktonic diatom
      Pseudo-nitzschia. This genus includes several species only distinguishable with
      the aid of molecular markers. Oxylipin profiles of cultured strains were obtained
      by reverse phase column on a liquid chromatograph equipped with UV photodiode
      detector and q-ToF mass spectrometer. Lipoxygenase compounds were mapped on
      phylogenies of the genus Pseudo-nitzschia inferred from the nuclear encoded hyper
      variable region of the LSU rDNA and the plastid encoded rbcL. Results showed that
      the genus Pseudo-nitzschia exhibits a rich and varied lipoxygenase metabolism of
      eicosapentaenoic acid (EPA), with a high level of specificity for oxylipin
      markers that generally corroborated the genotypic delineation, even among
      genetically closely related cryptic species. These results suggest that oxylipin
      profiles constitute additional identification tools for Pseudo-nitzschia species
      providing a functional support to species delineation obtained with molecular
      markers and morphological traits. The exploration of the diversity, patterns and
      plasticity of oxylipin production across diatom species and genera will also
      provide insights on the ecological functions of these secondary metabolites and
      on the selective pressures driving their diversification. 

PMID- 24014079
TI  - Phenotypic parameters predict time to normalization in infants with
      hypogammaglobulinemia.
AB  - PURPOSE: Infants with recurrent infection may be found to have
      hypogammaglobulinemia without impaired specific antibody responses. Many will be
      diagnosed with transient hypogammaglobulinemia of infancy. METHODS: This study
      used a parametric survival analysis of 100 infants with hypogammaglobulinemia to
      predict time to normalization. RESULTS: Aggregate initial immunoglobulins (IgG +
      IgA + IgM), as a percentage of age-adjusted normal, predicted time to resolution:
      median time to resolution for the infants in the lowest quartile of aggregate
      levels (<=81 % of age-adjusted lower limits) was greater than 5 years, with 34 %
      resolving in 3 years. For infants in the highest quartile (>=130 % of age
      adjusted lower limits), the median was 9.9 months, with 77 % resolving in 3 years
      (P = 0.008). Initial IgG level, as a percentage of age-adjusted normal, also
      predicted resolution: the median time in the lowest quartile (<=78 % of age
      adjusted lower limits) was greater than 5 years, with 36 % resolving in 3 years.
      In the highest quartile (>=128 %), the median time was 14.5 months, with 70 %
      resolving in 3 years (P = 0.010). Male sex was associated with more rapid
      resolution. The median time in males was 13 months, with 73 % resolution in 3
      years. The median time in females was greater than 5 years, with 32 % resolution
      in 3 years. CONCLUSIONS: These results suggest that if a term infant presents
      with hypogammaglobulinemia, protective specific antibody titers, and an absence
      of other known immune deficiency, initial immunoglobulin levels and sex may
      predict time to normalization.

PMID- 24014078
TI  - New insights of Microsporidial infection among asymptomatic aboriginal population
      in Malaysia.
AB  - BACKGROUND: Studies on microsporidial infection mostly focus on immunodeficiency
      or immunosuppressive individuals. Therefore, this cross-sectional study describes
      the prevalence and risk factors of microsporidiosis among asymptomatic
      individuals in Malaysia. METHODS/FINDINGS: Four hundred and forty seven stool
      samples were collected and examined for microsporidia after staining with Gram
      chromotrope Kinyoun. Demographic, socioeconomic, environmental, and behavioral
      information were collected by using a pre-tested questionnaire. Overall, 67 (15%)
      samples were positive for microsporidia. The prevalence of infection was
      significantly higher among individuals aged more than 15 years compared to those
      aged <15 years (OR = 1.97, 95% CI = 1.08, 3.62; P = 0.028). Furthermore, logistic
      regression analysis confirmed that the presence of other family members infected
      with microsporidia (OR = 8.45; 95% CI = 4.30, 16.62; P<0.001) and being a
      consumer of raw vegetables (OR = 2.05; 95% CI = 1.15, 3.66; P = 0.016) were the
      significant risk factors of this infection. CONCLUSIONS: These findings clearly
      show that exposure to microsporidia is common among Aboriginal population.
      Further studies using molecular approach on microsporidia isolates from
      asymptomatic individuals is needed to determine species-specific. The risk
      factors associated with microsporidiosis will help in identifying more clearly
      the sources of the infection in the environment that pose a risk for transmission
      so that preventive strategies can be implemented.

PMID- 24014080
TI  - Houston's rapid ozone increases: preconditions and geographic origins.
AB  - Many of Houston's highest 8-h ozone (O3) peaks are characterised by increases in
      concentrations of at least 40 ppb in 1 h, or 60 ppb in 2 h. These rapid increases
      are called non-typical O3 changes (NTOCs). In 2004, the Texas Commission on
      Environmental Quality (TCEQ) developed a novel emissions control strategy aimed
      at eliminating NTOCs. The strategy limited routine and short-term emissions of
      ethene, propene, 1,3-butadiene and butene isomers, collectively called highly
      reactive volatile organic compounds (HRVOCs), which are released from
      petrochemical facilities. HRVOCs have been associated with NTOCs through field
      campaigns and modelling studies. This study analysed wind measurements and O3,
      formaldehyde (HCHO) and sulfur dioxide (SO2) concentrations from 2000 to 2011 at
      25 ground monitors in Houston. NTOCs almost always occurred when monitors were
      downwind of petrochemical facilities. Rapid O3 increases were associated with low
      wind speeds; 75 % of NTOCs occurred when the 3-h average wind speed preceding the
      event was less than 6.5 km h-1. Statistically significant differences in HCHO
      concentrations were seen between days with and without NTOCs. Early afternoon
      HCHO concentrations were greater on NTOC days. In the morning before an observed
      NTOC event, however, there were no significant differences in HCHO concentrations
      between days with and without NTOCs. Hourly SO2 concentrations also increased
      rapidly, exhibiting behaviour similar to NTOCs. Oftentimes, the SO2 increases
      preceded a NTOC. These findings show that, despite the apparent success of
      targeted HRVOC emission controls, further restrictions may be needed to eliminate
      the remaining O3 events.

PMID- 24014081
TI  - How autism became autism: The radical transformation of a central concept of
      child development in Britain.
AB  - This article argues that the meaning of the word 'autism' experienced a radical
      shift in the early 1960s in Britain which was contemporaneous with a growth in
      epidemiological and statistical studies in child psychiatry. The first part of
      the article explores how 'autism' was used as a category to describe
      hallucinations and unconscious fantasy life in infants through the work of
      significant child psychologists and psychoanalysts such as Jean Piaget, Lauretta
      Bender, Leo Kanner and Elwyn James Anthony. Theories of autism were then
      associated both with schizophrenia in adults and with psychoanalytic styles of
      reasoning. The closure of institutions for 'mental defectives' and the growth in
      speech therapy services in the 1960s and 1970s encouraged new models for
      understanding autism in infants and children. The second half of the article
      explores how researchers such as Victor Lotter and Michael Rutter used the
      category of autism to reconceptualize psychological development in infants and
      children via epidemiological studies. These historical changes have influenced
      the form and function of later research into autism and related conditions.

PMID- 24014082
TI  - HIV positivity but not HPV/p16 status is associated with higher recurrence rate
      in anal cancer.
AB  - AIM: Human papillomavirus (HPV) is a pathogenic factor of squamous cell carcinoma
      in various mucosal locations, including anal carcinoma (ACA). It is also known
      that patients positive for HIV are at high risk of ACA. The goal of this study
      was to examine clinical outcome in ACA in relation to HPV/p16 positivity,
      histologic tumor differentiation, and HIV status. Patients with oropharyngeal
      cancers that are positive for HPV and show overexpression of p16 as well as
      having non-keratinizing/basaloid histology have been reported to have better
      outcomes following chemoradiation (CRT). However, such relationships in ACA
      remain unknown. METHODS: Forty-two patients with SCC of the anus treated with CRT
      between 1997 and 2009 were identified. The tumors were subclassified as either
      non-keratinizing (including basaloid) or keratinizing categories. HPV testing was
      performed using SPF10-PCR, and all cases were immunostained for p16. RESULTS:
      There were 23 men and 19 women; 43% of men and 11% of women were HIV-positive (p
      = 0.04). Fifty-five percent of patients had local disease (stages I and II) and
      41% were stages III and IV, with 4% stage unknown. All tumors were positive for
      high-oncogenic risk HPVs, and all were positive with p16 immunostain. Sixty-four
      percent of tumors were non-keratinizing/basaloid and 36 % were keratinizing. The
      keratinizing tumors were more common in HIV-positive patients (67%), whereas non
      keratinizing/basaloid tumors were more common in HIV-negative patients (77%) (p =
      0.008). Thirty-one percent of patients had recurrence of disease, including 50%
      HIV-positive patients and 23% HIV-negative patients (p = 0.09). There was no
      difference in the recurrence rate between non-keratinizing and keratinizing tumor
      subtypes (p = 0.80). The 24-month recurrence-free survival for the cohort was 66%
      (95% CI = 46%, 81%), with HIV-positive patients having worse recurrence-free
      survival compared to HIV-negative patients (HR = 2.85, 95% CI = 0.95, 8.53; p =
      0.06). CONCLUSION: The regional and distant failure rate was not related to
      HPV/p16 positivity or histologic differentiation of ACA; however, HIV positivity
      appeared to be associated with a higher recurrence rate and worse recurrence-free
      survival.

PMID- 24014083
TI  - Chromatin-modifying agents for epigenetic reprogramming and endogenous neural
      stem cell-mediated repair in stroke.
AB  - The recent explosion of interest in epigenetics and chromatin biology has made a
      significant impact on our understanding of the pathophysiology of cerebral
      ischemia and led to the identification of new treatment strategies for stroke,
      such as those that employ histone deacetylase inhibitors. These are key advances;
      however, the rapid pace of discovery in chromatin biology and innovation in the
      development of chromatin-modifying agents implies there are emerging classes of
      drugs that may also have potential benefits in stroke. Herein, we discuss how
      various chromatin regulatory factors and their recently identified inhibitors may
      serve as drug targets and therapeutic agents for stroke, respectively. These
      factors primarily include members of the repressor element-1 silencing
      transcription factor (REST)/neuron-restrictive silencer factor macromolecular
      complex, polycomb group (PcG) proteins, and associated chromatin remodeling
      factors, which have been linked to the pathophysiology of cerebral ischemia.
      Further, we suggest that, because of the key roles played by REST, PcG proteins
      and other chromatin remodeling factors in neural stem and progenitor cell (NSPC)
      biology, chromatin-modifying agents can be utilized not only to mitigate ischemic
      injury directly but also potentially to promote endogenous NSPC-mediated brain
      repair mechanisms. 

PMID- 24014084
TI  - High sensitive detection of carbohydrate binding proteins in an ELISA-solid phase
      assay based on multivalent glyconanoparticles.
AB  - Improved detection of anti-carbohydrate antibodies is a need in clinical
      identification of biomarkers for cancer cells or pathogens. Here, we report a new
      ELISA approach for the detection of specific immunoglobulins (IgGs) against
      carbohydrates. Two nanometer gold glyconanoparticles bearing oligosaccharide
      epitopes of HIV or Streptococcus pneumoniae were used as antigens to coat ELISA
      plates. A ~3,000-fold improved detection of specific IgGs in mice immunized
      against S. pneumoniae respect to the well known BSA-glycoconjugate ELISA was
      achieved. Moreover, these multivalent glyconanoparticles have been employed in
      solid phase assays to detect the carbohydrate-dependent binding of human
      dendritic cells and the lectin DC-SIGN. Multivalent glyconanoparticles in ELISA
      provide a versatile, easy and highly sensitive method to detect and quantify the
      binding of glycan to proteins and to facilitate the identification of biomarkers.

PMID- 24014085
TI  - Quantitative assessment of the association between MTHFR rs1801131 polymorphism
      and risk of liver cancer.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is one of the most important enzymes
      for folate metabolism which plays a key role in cell metabolism. MTHFR rs1801131
      (A1298C) polymorphism can decrease in vitro MTHFR enzyme activity and has been
      hypothesized to be associated with liver cancer risk. This study aimed to
      quantify the strength of the association between MTHFR rs1801131 polymorphism and
      liver cancer risk by performing a meta-analysis. We searched the PubMed and
      Wanfang databases for studies relating on the association between MTHFR rs1801131
      polymorphism and risk of liver cancer. Seven studies with 2,030 cases of liver
      cancer and 3,096 controls were finally included into the meta-analysis. Meta
      analysis of a total of seven studies showed that the homozygote genotype CC of
      MTHFR rs1801131 polymorphism was significantly associated with decreased risk of
      liver cancer (for CC versus AA: odds ratio (OR) = 0.65, 95% confidence interval
      (CI) 0.47-0.89, P = 0.007; for CC versus AA + AC: OR = 0.65, 95% CI 0.48-0.89, P
      = 0.006). Subgroup by race showed that the homozygote genotype CC of MTHFR
      rs1801131 polymorphism was significantly associated with decreased risk of liver
      cancer in Asians (CC versus AA: OR = 0.64, 95% CI 0.46-0.90, P = 0.010; for CC
      versus AA + AC: OR = 0.63, 95% CI 0.45-0.88, P = 0.007). However, the association
      in Caucasians was still unclear owing to the limited data available now. Thus,
      Asian individuals with the homozygote genotype CC of MTHFR rs1801131 polymorphism
      are significantly associated with decreased risk of liver cancer. The association
      in Caucasians needs further studies.

PMID- 24014086
TI  - An updated meta-analysis of the association between GSTM1 polymorphism and
      colorectal cancer in Asians.
AB  - Glutathione S-transferases (GSTs) are a large family of phase II detoxification
      enzymes that are expressed in many tissues and play critical roles in protecting
      hosts against cancer. The association of glutathione S-transferase M1 (GSTM1)
      polymorphism with susceptibility to colorectal cancer in Asians has not been well
      established. We performed a meta-analysis to quantitatively assess the
      association between GSTM1 polymorphism and colorectal cancer in Asians. We
      systematically searched the PubMed and Embase databases to identify the eligible
      studies. Finally, 17 eligible studies with 5,907 cases and 9,726 controls were
      included into the meta-analysis. The pooled odds ratio (OR) with its 95 %
      confidence intervals (95 %CI) was used to assess the association. The meta
      analysis of those included studies suggests that GSTM1 null genotype was
      significantly associated with colorectal cancer risk in Asians (OR = 1.14, 95 %CI
      = 1.013-1.29, P = 0.03). The cumulative meta-analyses showed a trend of an
      obvious association between the GSTM1 null genotype and risk of colorectal cancer
      in Asians as information accumulated by year. Thus, there is an obvious
      association between the GSTM1 null genotype and risk of colorectal cancer in
      Asians.

PMID- 24014087
TI  - CIP2A is overexpressed in osteosarcoma and regulates cell proliferation and
      invasion.
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a newly characterized
      oncoprotein involved in a variety of malignant tumors. However, its expression
      pattern and biological functions in osteosarcoma remain unclear. In the present
      study, CIP2A expression was analyzed in 51 human osteosarcoma specimens using
      immunohistochemistry. CIP2A siRNA was used in the MG-63 cell line, and the effect
      of CIP2A depletion on cell proliferation and invasion was evaluated. We found
      that CIP2A was overexpressed in 76.5 % (39/51) of osteosarcoma tissues, while
      normal bone tissues showed negative CIP2A expression. In addition, the positive
      rate of CIP2A expression was higher in stage IIB osteosarcoma than stage IIA
      cases. Knockdown of the CIP2A expression significantly reduced osteosarcoma cell
      proliferation and invasion, with decreased c-Myc expression and p-AKT expression.
      CIP2A depletion also facilitated apoptosis and inhibited MMP9 mRNA expression.
      Taken together, our data identified CIP2A as a critical oncoprotein involved in
      cell proliferation and invasion, which could serve as a therapeutic target in
      osteosarcoma.

PMID- 24014088
TI  - Association between the cytotoxic T-lymphocyte antigen 4 +49A/G polymorphism and
      bladder cancer risk.
AB  - Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a potent immunoregulatory molecule
      that suppresses antitumor response by downregulating T cell activation. The most
      studied CTLA-4 +49A/G polymorphism has been associated with various cancers
      risks. However, little is known about the association between CTLA-4 +49A/G
      polymorphism and bladder cancer risk. A hospital-based case-control study was
      conducted in 300 patients with bladder cancer and 300 healthy controls matched
      with age and sex. The CTLA-4 +49A/G polymorphism was genotyped using polymerase
      chain reaction-restriction fragment length polymorphism. Patients with bladder
      cancer had a significantly lower frequency of CTLA-4 +49GG genotype [odds ratio
      (OR) = 0.44, 95 % confidence interval (CI) = 0.23, 0.85; P = 0.01] and G allele
      (OR = 0.73, 95 % CI = 0.56, 0.96; P = 0.02) than healthy controls. When
      stratifying by the stage, grade, and histological type of bladder cancer, we
      found no statistical association. This is the first study to highlight the
      significant association between CTLA-4 +49A/G polymorphism and bladder cancer
      risk. Additional studies are needed to confirm this finding.

PMID- 24014089
TI  - Everolimus in combination with letrozole inhibit human breast cancer MCF-7/Aro
      stem cells via PI3K/mTOR pathway: an experimental study.
AB  - This study evaluated the effects of an mTOR inhibitor everolimus alone or in
      combination with letrozole on MCF-7/Aro (MCF-7 cells stably transfected with
      CYP19) in vitro and in vivo. In vitro studies, full-length CYP19 (aromatase) was
      cloned in a plasmid transfer vector pH beta-Aro and then transfected into MCF-7
      stem cells which were ESA(+)CD44(+)CD24(-/low) sorted by flow cytometry. MTT
      assays were used to quantify the inhibitory effect of the drugs on MCF-7/Aro stem
      cells (SCs) and non-stem cells (NSCs). Apoptosis and the cell cycle distributions
      of stem cells were examined by flow cytometry. The tumorigenicity of stem cells
      after treatment was investigated by soft agar colony formation assays. In vivo
      studies, the BALB/c mice were injected with MCF-7/Aro SCs, and the different
      treatments were administered. After necropsy, the expression of KI67, CD31, AKT1,
      phospho-AKT (Thr308), and mTOR was analyzed by immunohistochemistry. In vitro,
      compared with MCF-7/Aro NSCs, there were greater resistance to the standard
      treatment doses of letrozole and everolimus in MCF-7/Aro SCs (17- and 15-fold,
      respectively). Treatment with everolimus or letrozole resulted in growth
      inhibition of SCs in a dose-dependent manner. Compared with single-agent therapy,
      the combination of everolimus with letrozole was more effective in the inhibition
      of cell growth (P < 0.001) and tumorigenicity (P < 0.01). In addition, an
      increase in G1 cell cycle arrest and increases in early apoptosis were observed
      in the combination treatment group compared with either single-agent group. In
      vivo, the xenograft tumor sizes were significantly decreased in everolimus alone
      group compared to control group, and everolimus plus letrozole therapy was much
      more effective compared with either single agent alone (P < 0.01). Compared with
      everolimus alone, the combination of everolimus and letrozole reduced the
      expression of KI67, mTOR, and phospho-AKT (Thr308; P < 0.01). Everolimus has
      effective inhibition on aromatase-overexpressing stem cell in vitro and in vivo.
      The combination everolimus and letrozole could be more effective than either drug
      alone.

PMID- 24014090
TI  - Novel mutations in ADAMTSL2 gene underlying geleophysic dysplasia in families
      from United Arab Emirates.
AB  - BACKGROUND: Geleophysic dysplasia (GD) is an autosomal recessive disorder
      characterized by short stature, brachydactyly, stiff joints, thick skin, and
      cardiac valvular abnormalities that are often responsible for early death.
      Mutations in ADAMTSL2 and FBN1 genes have been shown to cause GD due to the
      dysregulation of transforming growth factor-beta signaling pathways. Small
      numbers of mutations in ADAMTSL2 have been reported so far in patients with GD
      type 1 (GD1). METHODS: In this study, we clinically evaluated two children from
      two consanguineous Arab families living in the United Arab Emirates with GD1. In
      addition we have sequenced all the coding exons of ADAMTSL2 gene using Sanger
      sequencing. RESULTS: The two patients exhibited most of the typical features of
      this rare bone dysplasia. Molecular analysis of the ADAMTSL2 gene revealed two
      novel homozygous missense mutations (c.938T>C, p.M313T and c.499G>A, p.D167N).
      The mutations segregated well in the studied families with the parents being
      heterozygous. In addition, bioinformatics analyses showed that these mutations
      are affecting conserved amino acids residues and thus strongly support their
      pathogenicity. CONCLUSION: We describe the clinical phenotypes of two patients
      with GD1 that are caused by two novel homozygous missense mutations in the
      ADAMTSL2 gene.

PMID- 24014092
TI  - Synthesis of aryl trimethylstannanes from aryl amines: a Sandmeyer-type
      stannylation reaction.
AB  - Sandmeyer-type stannylation: Stille coupling is one of the most powerful coupling
      reactions for C?C bond formation, whereas there are only limited methods to
      access aryl stannane compounds. A mild stannylation process based on a Sandmeyer
      type transformation using aromatic amines as the starting materials is described.
      DCE: 1,2-dichloroethane. 

PMID- 24014091
TI  - Substitutions at the opening of the Rubisco central solvent channel affect
      holoenzyme stability and CO2/O 2 specificity but not activation by Rubisco
      activase.
AB  - Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the initial
      step of carbon metabolism in photosynthesis. The holoenzyme comprises eight large
      subunits, arranged as a tetramer of dimers around a central solvent channel that
      defines a fourfold axis of symmetry, and eight small subunits, arranged as two
      tetramers at the poles of the axis. The phylogenetically divergent small-subunit
      loops between beta-strands A and B form the entrance to the solvent channel. In
      the green alga Chlamydomonas reinhardtii, Ile-58 from each of the four small
      subunit betaA-betaB loops defines the minimal diameter of the channel opening. To
      understand the role of the central solvent channel in Rubisco function, directed
      mutagenesis and transformation of Chlamydomonas were employed to replace Ile-58
      with Ala, Lys, Glu, Trp, or three Trp residues (I58W3) to close the entrance to
      the channel. The I58E, I58K, and I58W substitutions caused only small decreases
      in photosynthetic growth at 25 and 35  degrees C, whereas I58W3 had a substantial
      effect at both temperatures. The mutant enzymes had decreased carboxylation
      rates, but the I58W3 enzyme had decreases in both carboxylation and CO2/O2
      specificity. The I58E, I58W, and I58W3 enzymes were inactivated at lower
      temperatures than wild-type Rubisco, and were degraded at slower rates under
      oxidative stress. However, these mutant enzymes were activated by Rubisco
      activase at normal rates, indicating that the structural transition required for
      carboxylation is not affected by altering the solvent channel opening. Structural
      dynamics alone may not be responsible for these distant effects on the Rubisco
      active site. 

PMID- 24014094
TI  - Data generation for the Cox proportional hazards model with time-dependent
      covariates: a method for medical researchers.
AB  - The proliferation of longitudinal studies has increased the importance of
      statistical methods for time-to-event data that can incorporate time-dependent
      covariates. The Cox proportional hazards model is one such method that is widely
      used. As more extensions of the Cox model with time-dependent covariates are
      developed, simulations studies will grow in importance as well. An essential
      starting point for simulation studies of time-to-event models is the ability to
      produce simulated survival times from a known data generating process. This paper
      develops a method for the generation of survival times that follow a Cox
      proportional hazards model with time-dependent covariates. The method presented
      relies on a simple transformation of random variables generated according to a
      truncated piecewise exponential distribution and allows practitioners great
      flexibility and control over both the number of time-dependent covariates and the
      number of time periods in the duration of follow-up measurement. Within this
      framework, an additional argument is suggested that allows researchers to
      generate time-to-event data in which covariates change at integer-valued steps of
      the time scale. The purpose of this approach is to produce data for simulation
      experiments that mimic the types of data structures applied that researchers
      encounter when using longitudinal biomedical data. Validity is assessed in a set
      of simulation experiments, and results indicate that the proposed procedure
      performs well in producing data that conform to the assumptions of the Cox
      proportional hazards model.

PMID- 24014093
TI  - C1q-tumour necrosis factor-related protein 8 (CTRP8) is a novel interaction
      partner of relaxin receptor RXFP1 in human brain cancer cells.
AB  - We report a novel ligand-receptor system composed of the leucine-rich G-protein
      coupled relaxin receptor, RXFP1, and the C1q-tumour necrosis factor-related
      protein 8 (CTRP8) in human primary brain cancer, a tumour entity devoid of the
      classical RXFP1 ligands, RLN1-3. In structural homology studies and computational
      docking experiments we delineated the N-terminal region of the globular C1q
      region of CTRP8 and the leucine-rich repeat units 7 and 8 of RXFP1 to mediate
      this new ligand-receptor interaction. CTRP8 secreted from HEK293T cells,
      recombinant human (rh) CTRP8, and short synthetic peptides derived from the C1q
      globular domain of human CTRP8 caused the activation of RXFP1 as determined by
      elevated intracellular cAMP levels and the induction of a marked pro-migratory
      phenotype in established glioblastoma (GB) cell lines and primary cells from GB
      patients. Employing a small competitor peptide, we were able to disrupt the CTRP8
      RXFP1-induced increased GB motility. The CTRP8-RXFP1-mediated migration in GB
      cells involves the activation of PI3K and specific protein kinase C pathways and
      the increased production/secretion of the potent lysosomal protease cathepsin B
      (cathB), a known prognostic marker of GB. Specific inhibition of CTRP8-induced
      cathB activity effectively blocked the ability of primary GB to invade laminin
      matrices. Finally, co-immunoprecipitation studies revealed the direct interaction
      of human CTRP8 with RXFP1. Our results support a therapeutic approach in GB aimed
      at targeting multiple steps of the CTRP8-RXFP1 signalling pathway by a combined
      inhibitor and peptide-based strategy to block GB dissemination within the brain.

PMID- 24014095
TI  - Evaluation of hospital medication inventory policies.
AB  - As supply chain costs constitute a large portion of hospitals' operating expenses
      and with $27.7 billion spent by the US hospitals on drugs alone in 2009,
      improving medication inventory management provides a great opportunity to
      decrease the cost of healthcare. This study investigates different management
      approaches for a system consisting of one central storage location, the main
      pharmacy, and multiple dispensing machines located in each department. Each
      medication has a specific unit cost, availability from suppliers, criticality
      level, and expiration date. Event-driven simulation is used to evaluate the
      performance of several inventory policies based on the total cost and patient
      safety (service level) under various arrangements of the system defined by the
      number of drugs and departments, and drugs' criticality, availability, and
      expiration levels. Our results show that policies that incorporate drug
      characteristics in ordering decisions can address the tradeoff between patient
      safety and cost. Indeed, this study shows that such policies can result in higher
      patient safety and lower overall cost when compared to traditional approaches.
      Additional insights from this study allow for better understanding of the
      medication inventory system's dynamics and suggest several directions for future
      research in this topic. Findings of this study can be applied to help hospital
      pharmacies with managing their inventory. 

PMID- 24014096
TI  - N-methyl-D-aspartate receptor antibodies in post-herpes simplex virus
      encephalitis neurological relapse.
AB  - Herpes simplex virus encephalitis (HSVE) is a devastating condition that
      relapses, often with a chorea in children, despite adequate antiviral treatment.
      At relapse, evidence of viral replication is frequently absent, suggesting that
      the relapse may be immune-mediated. Seven children who had a neurological relapse
      following their initial encephalitis, identified from 20 cases of pediatric HSVE,
      were studied. Serum and/or cerebrospinal fluid (CSF) were tested for N-methyl-D
      aspartate receptor (NMDAR) and other antibodies previously reported in central
      nervous system autoimmunity. Five of the 7 relapsing children had
      choreoathetosis; 2 of these were NMDAR antibody-positive, 2 were negative (1 with
      HSV-positive CSF), and 1 was not available for testing. An additional patient,
      who relapsed with cognitive regression but with no movement disorder, was also
      NMDAR antibody-positive. In 2 of the NMDAR antibody-positive patients who were
      treated at relapse and in 1 who was treated only after 10 years of having a
      relapsing encephalopathy, a beneficial response was observed. Neurological
      relapses after HSVE may frequently be immune-mediated, particularly in children
      with chorea. NMDAR antibodies are common, and immunotherapy may be beneficial.

PMID- 24014097
TI  - Heterodera schachtii nematodes interfere with aphid-plant relations on Brassica
      oleracea.
AB  - Aboveground and belowground herbivore species modify plant defense responses
      differently. Simultaneous attack can lead to non-additive effects on primary and
      secondary metabolite composition in roots and shoots. We previously found that
      aphid (Brevicoryne brassicae) population growth on Brassica oleracea was reduced
      on plants that were infested with nematodes (Heterodera schachtii) prior (4
      weeks) to aphid infestation. Here, we examined how infection with root-feeding
      nematodes affected primary and secondary metabolites in the host plant and
      whether this could explain the increase in aphid doubling time from 3.8 to 6.7
      days. We hypothesized that the effects of herbivores on plant metabolites would
      depend on the presence of the other herbivore and that nematode-induced changes
      in primary metabolites would correlate with reduced aphid performance. Total
      glucosinolate concentration in the leaves was not affected by nematode presence,
      but the composition of glucosinolates shifted, as gluconapin concentrations were
      reduced, while gluconapoleiferin concentrations increased in plants exposed to
      nematodes. Aphid presence increased 4-methoxyglucobrassicin concentrations in
      leaves, which correlated positively with the number of aphids per plant.
      Nematodes decreased amino acid and sugar concentrations in the phloem. Aphid
      population doubling time correlated negatively with amino acids and glucosinolate
      levels in leaves, whereas these correlations were non-significant when nematodes
      were present. In conclusion, the effects of an herbivore on plant metabolites
      were independent of the presence of another herbivore. Nematode presence reduced
      aphid population growth and disturbed feeding relations between plants and
      aphids.

PMID- 24014098
TI  - Spatial and temporal instability of local biotic community mediate a form of
      aposematic defense in newts, consisting of carotenoid-based coloration and
      tetrodotoxin.
AB  - Most animals advertise their unprofitability to potential predators via
      conspicuous signals. Whether the strength of this aposematic signal indicates the
      quality and quantity of chemical defenses in animals is controversial. Here, we
      investigated the relationship between the conspicuousness of an aposematic signal
      and toxicity, which likely depends, at least in part, on dietary sources, in the
      newt Cynops pyrrhogaster. Our results indicate that the magnitude of the
      aposematic signal was not correlated with the amount of tetrodotoxin (TTX) and 6
      epi TTX of wild individuals among populations. Using atoxic newts, reared from
      eggs, we compared the ability to accumulate TTX from diets between mainland and
      island populations. Newts of a mainland population that exhibited a less
      conspicuous signal accumulated more TTX than did equivalent newts of an insular
      population that displayed a more conspicuous signal; this was unrelated to
      variation in the toxicity of wild individuals of these two populations. We also
      found toxicity of wild newts changed over approximately one generation (10 years)
      in both populations. These results indirectly suggest that environmental
      variance, such as fluctuations in TTX resources in nature, may obscure
      differences in the ability of wild newts to accumulate TTX, and that this
      variation may be responsible for a lack of correlation between the strength of a
      newt's signal and its toxicity in the wild. These results imply that toxicity of
      wild individuals likely is a phenotypic trait largely dependent on environmental
      conditions.

PMID- 24014099
TI  - Ischemic complications after pituitary surgery: a report of two cases.
AB  - BACKGROUND: Cerebral ischemic complications after pituitary surgery are not
      frequently reported. These vascular complications may be related to (1) direct
      trauma to the vessel wall, (2) compression of the internal carotid artery (ICA)
      due to pituitary apoplexy, (3) vasospasm secondary to subarachnoid hemorrhage or
      vasoactive tumor extract, or (4) hypothalamic injury. PATIENTS: We describe two
      cases where major vessel infarcts occurred after removal of pituitary tumor. One
      case has repeated episodes of thrombembolism probably due to a internal carotid
      artery (ICA) dissection triggered by minor intraoperative ICA injury during
      transsphenoidal excision. The other cases had a late-onset cerebral ischemia due
      vasospasm of middle cerebral artery after transcranial excision of a large
      pituitary tumor. RESULT: Both patients had a long hospital stay and were managed
      successfully with anticoagulant and antiplatelet drugs, aggressive supportive
      care in the intensive care unit, and rehabilitation. CONCLUSION: These cases
      highlight two different mechanisms of infarcts after pituitary surgery. The first
      case highlights the importance of ICA evaluation before surgery in elderly
      patients with risk factors, such as chronic smoking, hypertension, and
      atherosclerotic disease. Even minimal manipulation of the ICA can generate a
      cascade of thrombembolic events in such patients. The second case highlights the
      importance of observing the patient of a highly vascular giant pituitary adenoma
      in the hospital for a longer than usual time. Delayed vasospasm can occur like in
      aneurysmal subarachnoid hemorrhage and have a good outcome if detected early and
      managed judiciously.

PMID- 24014100
TI  - Association of imaging classification of intracranial cerebral atherosclerotic
      vascular stenosis in ischemic stroke and renalase gene polymorphisms.
AB  - Cerebral atherosclerosis vascular stenosis is a common etiology for ischemic
      stroke and a major factor in recurrent stroke and vascular mortality. Recent
      studies suggest that renalase plays a role in hypertension and ischemic stroke,
      and may be involved in atherosclerosis. The aim of the present study was to
      investigate whether there were correlations between single-nucleotide
      polymorphisms (SNPs) in the renalase gene and severity of intracranial cerebral
      atherosclerotic vascular stenosis in ischemic stroke patients as determined by
      imaging. A total of 212 ischemic stroke patients and 244 healthy controls from
      the north Chinese Han population were enrolled in this study. Polymerase chain
      reaction and ligase detection reaction were used for SNP analysis. We classified
      the case samples by severity of the intracranial cerebral atherosclerotic
      vascular stenosis. Allele, genotype, and haplotype were analyzed in cases and
      controls, and logistic regression was used to adjust for bias due to conventional
      stroke risk factors. The allele and the genotype of rs10887800 in the renalase
      gene were both associated with severe intracranial cerebral atherosclerotic
      vascular stenosis (p = 0.013 and p = 0.049, respectively). No association was
      observed with severity for SNP rs2576178 or SNP rs2296545. Our findings show that
      the SNP rs10887800 in the renalase gene is closely associated with severe
      intracranial cerebral atherosclerotic vascular stenosis in ischemic stroke
      patients of north Chinese Han origin.

PMID- 24014101
TI  - Plac1 (placenta-specific 1) is widely expressed during fetal development and is
      associated with a lethal form of hydrocephalus.
AB  - BACKGROUND: Plac1 is an X-linked gene essential for normal placental development.
      Plac1 ablation is associated with placentomegaly and intrauterine growth
      retardation. Additionally, Plac1-null mice exhibit reduced postnatal viability.
      This study was conducted as part of our ongoing examination of the postnatal
      phenotype associated with Plac1 ablation. METHODS: Plac1 was deleted in murine
      embryonic stem cells and bred against a C57BL/6 background. Mutant mice were
      genotyped using a polymerase chain reaction-based strategy. Embryonic Plac1
      expression was assessed by quantitative real-time polymerase chain reaction, in
      situ hybridization, and beta-galactosidase expression. RESULTS: A total of 20% of
      the surviving X(m-)Y (knockout) males as well as 10-15% of the X(m-)X females
      (mutant maternal allele) developed lethal hydrocephalus at 4-8 weeks. By
      contrast, XX(p-) hets (paternal null allele) did not. Plac1 mRNA expression was
      detected in the fetal brain that markedly decreased after birth. Plac1 mRNA
      expression localized to the hindbrain and lateral ventricles of wild-type
      embryos. Additionally, Plac1 expression was observed throughout the fetus
      including the fetal lungs, kidney, intestine, liver, and heart. Embryonic Plac1
      expression was paternally imprinted with partial escape of the paternal allele
      from complete inactivation. The Plac1 protein localized to the apical surface of
      the epithelial cells lining the developing airways of the lung and proximal renal
      tubules, consistent with its localization in the differentiated
      syncytiotrophoblast. CONCLUSION: Plac1 is expressed in the brain in a
      developmentally regulated manner and its absence is linked to increased risk for
      hydrocephalus. It is also widely expressed in fetal tissues expanding the
      existing paradigm to include direct tissue-specific roles during development.

PMID- 24014102
TI  - Tunable photochromism in air-stable, robust dithienylethene-containing phospholes
      through modifications at the phosphorus center.
AB  - Robust photoswitch: The photophysical and photochromic properties of a series of
      robust dithienylethene-containing phosphole derivatives can be readily tuned by
      simple modifications at the phosphorus center. Both the open and closed forms of
      the phosphole compounds are stable in benzene solution and in PMMA film in the
      dark. 

PMID- 24014104
TI  - SDF-1 restores angiogenesis synergistically with VEGF upon LDL exposure despite
      CXCR4 internalization and degradation.
AB  - AIMS: Angiogenesis is compromised under conditions of hypercholesterolaemia.
      Since disturbed angiogenesis predisposes to ischaemic injuries, efforts have been
      made to promote angiogenesis by delivery of growth factors. How stromal cell
      derived growth factor (SDF)-1 influences angiogenesis under conditions reflecting
      hypercholesterolaemia was unknown. METHODS AND RESULTS: We investigated the
      effects of SDF-1, administered alone or in combination with vascular endothelial
      growth factor (VEGF), on angiogenesis using proliferation, transwell migration,
      and Matrigel-based tube formation assays with human umbilical vein endothelial
      cells that were exposed to low-density lipoprotein (LDL). We observed that SDF-1
      dose-dependently enhanced angiogenesis, but only partly reversed the LDL-mediated
      suppression of angiogenesis. Reduced abundance of SDF-1's receptor, CXCR4, was
      noted on the surface of LDL-exposed endothelial cells. In subcellular
      localization studies combined with pharmacological experiments, we showed that
      the loss of CXCR4 resulted from its internalization and degradation. SDF-1
      synergistically increased angiogenesis when combined with VEGF. As a consequence,
      angiogenesis was fully restored. SDF-1 reduced oxidized LDL formation and
      increased the anti-oxidant capacity of endothelial cells, most strongly when
      administered together with VEGF. CONCLUSION: Combination therapies of growth
      factors, specifically SDF-1 and VEGF, might enhance angiogenesis more
      successfully than monotherapies under conditions of hypercholesterolaemia.

PMID- 24014103
TI  - FAS-1377 G/A (rs2234767) polymorphism and cancer susceptibility: a meta-analysis
      of 17,858 cases and 24,311 controls.
AB  - BACKGROUND AND OBJECTIVES: Disruption of apoptosis has been implicated in
      carcinogenesis. Specifically, various single-nucleotide polymorphisms (SNPs) in
      apoptotic genes, such as FAS-1377 G/A SNP, have been associated with cancer risk.
      FAS-1377 G/A SNP has been shown to alter FAS gene promoter transcriptional
      activity. Down-regulation of FAS and cell death resistance is key to many
      cancers, but an association between FAS-1377 G/A SNP and cancer risk is
      uncertain. Therefore, we conducted a meta-analysis of the current literature to
      clarify this relationship. METHODOLOGY/PRINCIPAL FINDINGS: From PubMed and
      Chinese language (CNKI and WanFang) databases, we located articles published up
      to March 5, 2013, obtaining 44 case-control studies from 41 different articles
      containing 17,858 cases and 24,311 controls based on search criteria for cancer
      susceptibility related to the FAS gene -1377 G/A SNP. Odds ratios (ORs) and 95%
      confidence intervals (CI) revealed association strengths. Data show that the 
      1377 G allele was protective against cancer risk. Similar associations were
      detected in "source of control," ethnicity and cancer type subgroups. Lower
      cancer risk was found in both smokers with a GG+GA genotype and in non-smokers
      with the GG+GA genotype, when compared to smokers and nonsmokers with the AA
      genotype. Males carrying the -1377G allele (GG+GA) had lower cancer incidence
      than those with the AA genotype. Individuals who carried both FAS
      1377(GG+GA)/FASL-844(TT+TC) genotypes appeared to have lower risk of cancer than
      those who carried both FAS-1377 AA/FASL-844 CC genotypes.
      CONCLUSIONS/SIGNIFICANCE: The FAS-1377 G/A SNP may decrease cancer risk. Studies
      with larger samples to study gene-environment interactions are warranted to
      understand the role of FAS gene polymorphisms, especially -1377 G/A SNP, in
      cancer risk.

PMID- 24014105
TI  - Is the image quality of I-124-PET impaired by an automatic correction of prompt
      gammas?
AB  - OBJECTIVES: The aim of this study is to evaluate the quality of I-124 PET images
      with and without prompt gamma compensation (PGC) by comparing the recovery
      coefficients (RC), the signal to noise ratios (SNR) and the contrast to F-18 and
      Ga-68. Furthermore, the influence of the PGC on the quantification and image
      quality is evaluated. METHODS: For measuring the image quality the NEMA NU2-2001
      PET/SPECT-Phantom was used containing 6 spheres with a diameter between 10 mm and
      37 mm placed in water with different levels of background activity. Each sphere
      was filled with the same activity concentration measured by an independently
      cross-calibrated dose calibrator. The "hot" sources were acquired with a full 3D
      PET/CT (Biograph mCT(r), Siemens Medical USA). Acquisition times were 2 min for F
      18 and Ga-68, and 10 min for I-124. For reconstruction an OSEM algorithm was
      applied. For I-124 the images were reconstructed with and without PGC. For the
      calculation of the RCs the activity concentrations in each sphere were
      determined; in addition, the influence of the background correction was studied.
      RESULTS: The RCs of Ga-68 are the smallest (79%). I-124 reaches similar RCs (87%
      with PGC, 84% without PGC) as F-18 (84%). showing that the quantification of I
      124 images is similar to F-18 and slightly better than Ga-68. With background
      activity the contrast of the I-124 PGC images is similar to Ga-68 and F-18 scans.
      There was lower background activity in the I-124 images without PGC, which
      probably originates from an overcorrection of the scatter contribution.
      Consequently, the contrast without PGC was much higher than with PGC. As a
      consequence PGC should be used for I-124. CONCLUSIONS: For I-124 there is only a
      slight influence on the quantification depending on the use of the PGC. However,
      there are considerable differences with respect to I-124 image quality.

PMID- 24014106
TI  - Effects of eugenol on T-type Ca2+ channel isoforms.
AB  - Eugenol has been used as an analgesic in dentistry. Previous studies have
      demonstrated that voltage-gated Na(+) channels and high-voltage-activated Ca(2+)
      channels expressed in trigeminal ganglion (TG) neurons sensing dental pain are
      molecular targets of eugenol for its analgesic effects. However, it has not been
      investigated whether eugenol can affect T-type Ca(2+) channels, which are known
      to be detected in the afferent neurons. In this report, we investigate how
      eugenol can influence cloned T-type channel isoforms expressed in HEK293 cells,
      using whole-cell patch clamp. Application of eugenol inhibited Cav3.1, Cav3.2,
      and Cav3.3 currents in a concentration-dependent manner with IC50 values of 463,
      486, and 708 MUM, respectively. Eugenol was found to negatively shift the steady
      state inactivation curves of the T-type channel isoforms, but it did not shift
      their activation curves. In addition, eugenol had little effect on the current
      kinetics of Cav3.1 and Cav3.2, but it accelerated the inactivation kinetics of
      Cav3.3 currents. Reduction of channel availability enhanced eugenol inhibition
      sensitivity for Cav3.1 and Cav3.2, but not for Cav3.3. Moreover, eugenol
      inhibition of T-type channel isoforms was found to be use dependent. Finally, we
      show that the T-type currents recorded from rat TG neurons were inhibited by
      eugenol with a similar potency to Cav3.1 and Cav3.2 isoforms. Taken together, our
      findings suggest that T-type Ca(2+) channels are additional molecular targets for
      the pain-relieving effects of eugenol. 

PMID- 24014107
TI  - Prevention science supplemental issue commentary promoting healthy sexual
      practices: what we have learned from 100 years of work.

PMID- 24014108
TI  - The study of absorption kinetics of berberine based on portal vein in rat, and
      the influence of verapamil and borneol to its absorption ability by UHPLC method.
AB  - This paper aims to investigate the portal-vein absorption kinetics of berberine
      in rat, and the influence of P-gp inhibitors such as verapamil and borneol, to
      its absorption ability. In the paper, a validated UHPLC method was established to
      determine the berberine in plasma, and the portal-vein absorption model was
      applied to conduct the pharmacokinetic study. Animals were divided into four
      groups as follow: group berberine group (BG); group verapamil + berberine group
      (VBG); group borneol + berberine group (BBG) and group long-term use of borneol +
      berberine group (LBBG). Plasma samples were obtained at regular time intervals
      after administration and separated on Agilent 1290 Infinity UHPLC instrument. The
      method showed good linearity (r = 0.9988) over wide dynamic ranges (4.08-163.20
      ng/mL). Variations within- and between-batch never exceeded 7.58 and 2.21 %,
      respectively. The extraction recovery rates ranged from 85.34 to 111.62 %. We
      discovered that the AUC of four group exhibited no significant differences (P >
      0.05), and co-administration of berberine with borneol of group BBG and group
      LBBG in advance could both reduce the T max and C max as compared to group BG (P
      < 0.05), while co-administration of verapamil seems to have had little influence
      to berberine's absorption ability.

PMID- 24014109
TI  - An exploration of social circles and prescription drug abuse through Twitter.
AB  - BACKGROUND: Prescription drug abuse has become a major public health problem.
      Relationships and social context are important contributing factors. Social media
      provides online channels for people to build relationships that may influence
      attitudes and behaviors. OBJECTIVE: To determine whether people who show signs of
      prescription drug abuse connect online with others who reinforce this behavior,
      and to observe the conversation and engagement of these networks with regard to
      prescription drug abuse. METHODS: Twitter statuses mentioning prescription drugs
      were collected from November 2011 to November 2012. From this set, 25 Twitter
      users were selected who discussed topics indicative of prescription drug abuse.
      Social circles of 100 people were discovered around each of these Twitter users;
      the tweets of the Twitter users in these networks were collected and analyzed
      according to prescription drug abuse discussion and interaction with other users
      about the topic. RESULTS: From November 2011 to November 2012, 3,389,771 mentions
      of prescription drug terms were observed. For the 25 social circles (n=100 for
      each circle), on average 53.96% (SD 24.3) of the Twitter users used prescription
      drug terms at least once in their posts, and 37.76% (SD 20.8) mentioned another
      Twitter user by name in a post with a prescription drug term. Strong correlation
      was found between the kinds of drugs mentioned by the index user and his or her
      network (mean r=0.73), and between the amount of interaction about prescription
      drugs and a level of abusiveness shown by the network (r=0.85, P<.001).
      CONCLUSIONS: Twitter users who discuss prescription drug abuse online are
      surrounded by others who also discuss it-potentially reinforcing a negative
      behavior and social norm.

PMID- 24014110
TI  - Evidence of serologic activity in chronic hepatitis B after surface antigen
      (HBsAg) seroclearance documented by conventional HBsAg assay.
AB  - BACKGROUND: Possible serologic activity after hepatitis B surface antigen (HBsAg)
      seroclearance documented by conventional assays in chronic hepatitis B (CHB) has
      not been thoroughly investigated. METHODS: We determined the levels of serum
      hepatitis B virus (HBV) DNA, hepatitis B core-related antigen (HBcrAg), and
      linearized HBsAg (CLEIA prototype) in 329 CHB patients (72.0% male) after HBsAg
      seroclearance was documented by a conventional HBsAg assay. RESULTS: The median
      interval between presentation and HBsAg seroclearance was 69.4 months. The median
      age at HBsAg seroclearance was 50 years. Assays for serum HBV DNA, HBcrAg, and
      linearized HBsAg were performed at a median time interval of 11.2 months after
      HBsAg loss. Linearized HBsAg and HBcrAg were detectable in 85 (25.8%) and 69
      (21%) patients, respectively, and one or both serologic markers were detectable
      in 133 patients (40.4%). Serum HBV DNA was detectable in only 7 patients (2.1%).
      There was no correlation between linearized HBsAg and HBcrAg levels (r = 0.095, p
      = 0.924). The incidences of detectable linearized HBsAg and HBcrAg did not differ
      between patient samples taken at 6-12 and >12 months after HBsAg seroclearance (p
      = 0.146 and 0.079, respectively). Among patients with detectable serologic
      markers, median levels of linearized HBsAg (p = 0.581) and HBcrAg (p = 0.951) did
      not significantly change with time after HBsAg seroclearance. CONCLUSION: Using
      novel HBcrAg and linearized HBsAg assays, viral serologic activity after HBsAg
      seroclearance was demonstrated in more than 40% of CHB patients. These tests have
      potential applications in diagnosing and prognosticating CHB patients with HBsAg
      seroclearance.

PMID- 24014111
TI  - Cancer cell-derived lymphotoxin mediates reciprocal tumour-stromal interactions
      in human ovarian cancer by inducing CXCL11 in fibroblasts.
AB  - We have investigated the role of cytokine lymphotoxin in tumour-stromal
      interactions in human ovarian cancer. We found that lymphotoxin overexpression is
      commonly shared by the cancer cells of various ovarian cancer subtypes, and
      lymphotoxin-beta receptor (LTBR) is expressed ubiquitously in both the cancer
      cells and cancer-associated fibroblasts (CAFs). In monoculture, we showed that
      ovarian cancer cells are not the major lymphotoxin-responsive cells. On the other
      hand, our co-culture studies demonstrated that the cancer cell-derived
      lymphotoxin induces chemokine expression in stromal fibroblasts through LTBR-NF
      kappaB signalling. Amongst the chemokines being produced, we found that
      fibroblast-secreted CXCL11 promotes proliferation and migration of ovarian cancer
      cells via the chemokine receptor CXCR3. CXCL11 is highly expressed in CAFs in
      ovarian cancer biopsies, while CXCR3 is found in malignant cells in primary
      ovarian tumours. Additionally, the overexpression of CXCR3 is significantly
      associated with the tumour grade and lymph node metastasis of ovarian cancer,
      further supporting the role of CXCR3, which interacts with CXCL11, in promoting
      growth and metastasis of human ovarian cancer. Taken together, these results
      demonstrated that cancer-cell-derived lymphotoxin mediates reciprocal tumour
      stromal interactions in human ovarian cancer by inducing CXCL11 in fibroblasts.
      Our findings suggest that lymphotoxin-LTBR and CXCL11-CXCR3 signalling represent
      therapeutic targets in ovarian cancer.

PMID- 24014112
TI  - The Effects of a Between-Wave Incentive Experiment on Contact Update and
      Production Outcomes in a Panel Study.
AB  - Since 1969, families participating in the U.S. Panel Study of Income Dynamics
      (PSID) have been sent a mailing asking them to update or verify their contact
      information in order to keep track of their whereabouts between waves. Having
      updated contact information prior to data collection is associated with fewer
      call attempts, less tracking, and lower attrition. Based on these advantages, two
      experiments were designed to increase response rates to the between-wave contact
      mailing. The first experiment implemented a new protocol that increased the
      overall response rate by 7 - 10 percentage points compared to the protocol in
      place for decades on the PSID. This article provides results from the second
      experiment which examines the basic utility of the between-wave mailing,
      investigates how incentives affect article cooperation to the update request and
      field effort, and attempts to identify an optimal incentive amount.
      Recommendations for the use of contact update strategies in panel studies are
      made.

PMID- 24014113
TI  - IMD-0354 targets breast cancer stem cells: a novel approach for an adjuvant to
      chemotherapy to prevent multidrug resistance in a murine model.
AB  - Although early detection of breast cancer improved in recent years, prognosis of
      patients with late stage breast cancer remains poor, mostly due to development of
      multidrug resistance (MDR) followed by tumor recurrence. Cancer stem cells
      (CSCs), with higher drug efflux capability and other stem cell-like properties,
      are concentrated in a side population (SP) of cells, which were proposed to be
      responsible for MDR and tumor repopulation that cause patients to succumb to
      breast cancer. Therefore, targeting of CSCs as an adjuvant to chemotherapy should
      be able to provide a more effective treatment of this disease. Here, we used IMD
      0354, an inhibitor of NF-kappaB, identified for targeting CSCs, in a combination
      therapy with doxorubicin encapsulated in targeted nanoparticles. IMD-0354 did
      target CSCs, evidenced by a decrease in the SP, demonstrated by the inhibition of
      the following: dye/drug efflux, reduction in ABC transporters as well as in
      colony formation in soft agar and low attachment plates. Decrease of stem-like
      gene expression of Oct4, Nanog and Sox2, and apoptosis resistance related to the
      Survivin gene also was observed after treatment with this compound. In addition,
      IMD-0354 targeted non-CSCs as indicated by reducing viability and increasing
      apoptosis. Targeted drug delivery, achieved with a legumain inhibitor, proved to
      enhance drug delivery under hypoxia, a hallmark of the tumor microenvironment,
      but not under normoxia. Together, this allowed a safe, non-toxic delivery of both
      anticancer agents to the tumor microenvironment of mice bearing syngeneic
      metastatic breast cancer. Targeting both bulk tumor cells with a chemotherapeutic
      agent and CSCs with IMD-0354 should be able to reduce MDR. This could eventually
      result in decreasing tumor recurrences and/or improve the outcome of metastatic
      disease. 

PMID- 24014114
TI  - Efficient cellulose solvent: quaternary ammonium chlorides.
AB  - Pure quaternary tetraalkylammonium chlorides with one long alkyl chain dissolved
      in various organic solvents constitute a new class of cellulose solvents. The
      electrolytes are prepared in high yields and purity by Menshutkin quaternization,
      an inexpensive and easy synthesis route. The pure molten tetraalkylammonium
      chlorides dissolve up to 15 wt% of cellulose. Cosolvents, including N,N
      dimethylacetamide (DMA), may be added in large excess, leading to a system of
      decreased viscosity. Contrary to the well-established solvent DMA/LiCl, cellulose
      dissolves in DMA/quaternary ammonium chlorides without any pretreatment. Thus,
      the use of the new solvent avoids some disadvantages of DMA/LiCl and ionic
      liquids, the most extensively employed solvents for homogeneous cellulose
      chemistry. 

PMID- 24014115
TI  - Activin A: a potential therapeutic target for characterizing and stopping joint
      pain early in rheumatoid arthritis patients.
AB  - It is common for rheumatoid arthritis patients to suffer from persistent joint
      pain for decades during their lifetime. Activin A, a member of the transforming
      growth factor beta superfamily, which plays a role in the very early phase of
      inflammatory processes, can also induce pain behaviors. In view of the
      contribution of synovial inflammation to the progression of rheumatoid arthritis,
      here we present the hypothesis that activin A may be a potential therapeutic
      target, serving as a marker for joint pain in which inflammatory processes are
      involved and as a target for early intervention. 

PMID- 24014117
TI  - Three Generation Family Households: Differences by Family Structure at Birth.
AB  - Using data from the Fragile Families and Child Well-being Study (N=4,898), this
      study investigates how the share, correlates, transition patterns, and duration
      of three generation households vary by mother's relationship status at birth.
      Nine percent of married mothers, 17 % of cohabiting, and 45% of single mothers
      live in a three generation family household at the birth of the child. Incidence
      over time is much higher and most common among single mother households, 60% live
      in a three generation family household in at least one wave. Economic need,
      culture, and generational needs are associated with living in a three generation
      household and correlates vary by mother's relationship status. Three generation
      family households are short lived and transitions are frequent. Kin support
      through coresidence is an important source of support for families with young
      children and in particular families that are unwed at the birth of their child.

PMID- 24014116
TI  - Age-period-cohort models using smoothing splines: a generalized additive model
      approach.
AB  - Age-period-cohort (APC) models are used to analyze temporal trends in disease or
      mortality rates, dealing with linear dependency among associated effects of age,
      period, and cohort. However, the nature of sparseness in such data has severely
      limited the use of APC models. To deal with these practical limitations and
      issues, we advocate cubic smoothing splines. We show that the methods of
      estimable functions proposed in the framework of generalized linear models can
      still be considered to solve the non-identifiability problem when the model
      fitting is within the framework of generalized additive models with cubic
      smoothing splines. Through simulation studies, we evaluate the performance of the
      cubic smoothing splines in terms of the mean squared errors of estimable
      functions. Our results support the use of cubic smoothing splines for APC
      modeling with sparse but unaggregated data from a Lexis diagram.

PMID- 24014118
TI  - To cease or 'de-cyst'? The evaluation and management of pancreatic cystic
      lesions.
AB  - Due to the widespread use of cross-sectional imaging and advances in imaging
      technology, pancreatic cystic lesions are increasingly being detected. The
      diagnosis and management of such cysts remains challenging and continues to
      evolve. Different pancreatic cyst types have varying malignant potential. Thus,
      accurate cyst characterization is essential to appropriate management; the most
      clinically important distinction is differentiating mucinous lesions, which have
      malignant potential and may benefit from surgical resection, from non-mucinous
      cystic lesions. Endoscopic ultrasound with fine needle aspiration with cytologic,
      chemical,, and tumor marker analysis appears to be the best currently available
      method for accurately characterizing a cyst's malignant potential, and therefore
      impacts the most important management decision for a pancreatic cyst-continued
      surveillance or surgical resection. 

PMID- 24014119
TI  - EUS access to the biliary tree.
AB  - EUS-guided biliary access procedures can target the gallbladder or the bile duct
      for drainage in selected cases. EUS-guided gallbladder drainage offers comparable
      results to percutaneous cholecystostomy in high-surgical risk patients with acute
      cholecystitis refractory to medical treatment. The procedure is not yet widely
      available. Novel lumen-apposing stents may improve long-term outcomes, resulting
      in rapid dissemination. EUS access to the bile duct is coupled with ERCP
      techniques into a hybrid procedure, endosono-cholangiopancreatography (ESCP).
      ESCP admits six variant approaches to bile duct drainage based on the combination
      of two access routes (intrahepatic and extrahepatic) with three drainage routes:
      transmural, retrograde transpapillary and antegrade transpapillary. A thousand
      ESCP cases have been reported to date with good outcomes. When the expertise is
      available, ESCP is increasingly replacing percutaneous transhepatic biliary
      drainage to provide biliary drainage in patients in whom ERCP is not feasible,
      predominantly in the setting of palliation, but not limited to it.

PMID- 24014120
TI  - New insights in gastroesophageal reflux, esophageal function and gastric emptying
      in relation to dysphagia before and after anti-reflux surgery in children.
AB  - In children with gastroesophageal reflux (GER) disease refractory to
      pharmacological therapies, anti-reflux surgery (fundoplication) may be a
      treatment of last resort. The applicability of fundoplication has been hampered
      by the inability to predict which patient may benefit from surgery and which
      patient is likely to develop post-operative dysphagia. pH impedance measurement
      and conventional manometry are unable to predict dysphagia, while the role of
      gastric emptying remains poorly understood. Recent data suggest that the
      selection of patients who will benefit from surgery might be enhanced by
      automated impedance manometry pressure-flow analysis (AIM) analysis, which
      relates bolus movement and pressure generation within the esophageal lumen. 

PMID- 24014121
TI  - Patient-control association study of the Leucine-Rich repeat kinase 2 (LRRK2)
      gene in South African Parkinson's disease patients.

PMID- 24014122
TI  - Prenatal diagnosis of BMD in Morocco: evolution and limits.
AB  - The muscular dystrophy is a group of inherited disorders characterized in the
      most of cases by progressive muscle weakness. The best known are X-linked
      disorder Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD).
      BMD is a milder form of the disease with a later age of onset and a slower
      clinical progression. The DMD gene, located on Xp21, is the largest human gene in
      the human genome (2.3 Mb). DMD gene consists of 79 exons and codes for dystrophin
      protein. A 9-year-old boy, who experienced symptoms of the disease, was admitted
      to the Casablanca University Children's Hospital. The patient, with no known
      family history of significant muscle disease, was first examined at 4 years of
      age because of walking difficulties and a limited hands force. Blood tests
      revealed elevated serum levels of creatine kinase (7.60 U/L). The electromyogram
      showed myopathic changes, consisting of polyphasic potentials, and the muscular
      biopsy revealed dystrophic aspect. Analysis of the dystrophin-encoding gene by
      PCR deletion analysis of the dystrophin gene was performed by multiplex PCR
      primer sets of Chamberlain and Beggs. The analysis showed a deletion of exons 45
      to 49. Mother genetic testing showed the heterozygosis deletion.

PMID- 24014125
TI  - The prevalence, variety and impact of wrist problems in elite professional
      golfers on the European Tour.
AB  - OBJECTIVES: Golf is a popular sport played by an estimated 57 million people.
      Previous studies on wrist injuries in elite golfers have been of simple design
      and have demonstrated such injuries to be frequent, although no studies report
      the incidence, variety, severity or impact on the activity of wrist injuries in
      detail. This prospective cross-sectional study assesses these factors in a cohort
      of elite professional golfers. METHODS: European Tour golfers eligible to compete
      at the 2009 BMW PGA Championship at Wentworth were studied. Study design involved
      the completion of a structured questionnaire supplemented by interview and
      examination when required, with performance statistics provided by the European
      Tour. The severity of injury was assessed by the number of missed tournaments and
      the amount of time of missed practice. RESULTS: 128 of 153 eligible golfers,
      (84%) completed the study with 38 golfers (30%) reporting 43 problems. The
      majority of injuries (67%) occurred in the leading wrist at the most common
      location, the ulnar side of the wrist (35%). 87% of all ulnar-sided and 100% of
      radial-sided problems were in the leading wrist. CONCLUSIONS: There were clear
      side differences reported by the players with the lead wrist demonstrating much
      higher injury rates in all areas. The most significant injury, in terms of
      absence from competition, was extensor carpi ulnaris tendon subluxation. Specific
      injuries are explained in relation to the biomechanics of the golf swing. Most
      structural injuries have a specific treatment and rehabilitation plan, which can
      involve significant periods of time away from the sport, while the management of
      many of the more minor problems is through alterations in technique or practice
      regimes, aiming to keep a golfer playing during recovery.

PMID- 24014123
TI  - Upregulated expression of NF-YC contributes to neuronal apoptosis via
      proapoptotic protein bim in rats' brain hippocampus following middle cerebral
      artery occlusion (MCAO).
AB  - Cerebral ischemia represents a severe brain injury that could lead to significant
      neuronal damage and death. In this study, we performed a middle cerebral artery
      occlusion (MCAO) in adult rats and observed that a subunit of nuclear factor-Y
      (NF-Y) transcriptional factor, NF-YC, was accumulated in rat hippocampal CA1
      neurons. Immunochemistrical and immunofluorescent analysis revealed that NF-YC
      was primarily expressed in the nucleus of neurons. Meanwhile, we found that the
      changes of bim, one of the target genes of NF-Y, were consistent with the
      expression of NF-YC and Bim was mainly located in the NF-YC positive cells.
      Moreover, there was a concomitant upregulation of active caspase-3 and TUNEL
      positive cells. Taken together, these results suggested that the upregulation of
      NF-YC might play an important role in the pathophysiology via proapoptotic
      protein Bim after MCAO and further research is needed to have a better
      understanding of its function and mechanism. 

PMID- 24014126
TI  - Broken symmetry of an adsorbed molecular switch determined by scanning tunneling
      spectroscopy.
AB  - An asymmetric turn: Scanning tunneling spectroscopy has been used to analyze the
      structure of tris[4-(phenylazo)phenyl)]amine on a Au(111) surface. A degenerate
      marker state serves as a sensitive probe for the structure of the adsorbed
      molecules. 

PMID- 24014128
TI  - The functional Aquaporin 1 -783G/C-polymorphism is associated with survival in
      patients with glioblastoma multiforme.
AB  - BACKGROUND: Despite a dismal prognosis, variability exists regarding the survival
      time in patients with glioblastoma-multiforme (GBM), which may be explained by
      genetic variation. A possible candidate-gene for such variation is Aquaporin-1
      (AQP1), since Aquaporin-1-expression influences the pathogenesis and outcome of
      various malignancies. Functional genetic variants in the promoter of AQP1,
      modifying Aquaporin-1-expression, could be associated with altered survival in
      patients with GBM. METHODS: We sequenced the human AQP1-promoter to detect novel
      sequence variants, which might impact on Aquaporin-1-expression and tested the
      hypothesis, that functional single nucleotide polymorphisms are associated with
      different survival-times of patients suffering from GBM. RESULTS: Sequencing the
      AQP1-promoter revealed a novel -783G/C-polymorphism. Reporter-assays showed that
      substitution of G for C was associated both with increased transcriptional
      activation of the AQP1-promoter by serum and with increased AQP1 mRNA expression.
      Finally, we assessed in a cohort of 155 Caucasian patients with GBM whether the
      functional single-nucleotide-783G/C-polymorphism is associated with survival
      time. Cox-regression analyses revealed the AQP1 -783G/C genotype status as an
      independent prognostic-factor when jointly considering other predictors of
      survival. Homozygous CC subjects had a significantly worse outcome compared to
      GC/GG genotypes (hazard ratio: 3.09; 95% CI, 1.43-6.65; P = 0.004). CONCLUSIONS:
      Our findings suggest the novel AQP1 polymorphism as a survival prognosticator in
      patients suffering from GBM that could help to identify a subgroup of patients at
      high risk for death. Further studies are necessary to reveal the exact molecular
      mechanisms.

PMID- 24014129
TI  - Changes in the expression levels of tight junction components during
      reconstruction of tight junction from mucosal lesion by intestinal
      ischemia/reperfusion.
AB  - Tight junction (TJ) is composed of the most apical components of the
      intercellular junctional complex in epithelial cells; TJ has cell polarity and
      functions as a major determinant of epithelial barrier function. In this study,
      to clarify the components of TJ required for its reconstruction and functional
      acquisition, we examined the changes in intestinal mucosal structure that
      depended on mucosal lesion by intestinal I/R, that is, the changes in mRNA and
      protein expression of the claudin family and scaffold proteins. We used an in
      vivo intestinal I/R model made using the spring scale and surgical sutures, and
      examined the mRNA and protein expression levels of TJ components by real-time RT
      PCR and Western blotting, respectively. Changes in mRNA and protein expression
      levels of TJ components by intestinal I/R were observed. Among them,
      characteristic changes were observed in claudin-2 and claudin-4. In addition, the
      expression behavior of multi-PDZ domain protein (MPDP) mRNA was similar to that
      of claudin-4. In conclusion, in the recovery process of TJ from mucosal lesion by
      intestinal I/R, it was suggested that claudin-2 and claudin-4 strongly
      participate in the reconstruction and functional acquisition of TJ, respectively.
      Furthermore, it was suggested that MPDZ, which is scaffold protein, also has an
      important role in these processes.

PMID- 24014130
TI  - Molecular testing for cystic fibrosis carrier status practice guidelines:
      recommendations of the National Society of Genetic Counselors.
AB  - PURPOSE: To provide practice recommendations for genetic counselors whose clients
      are considering cystic fibrosis (CF) carrier testing or seeking information
      regarding CF molecular test results. The goals of these recommendations are to:
      1) Provide updated information about the natural history, diagnosis, and
      treatment of CF and related conditions. 2) Supplement genetic counselors'
      knowledge and understanding of the available carrier screening and diagnostic
      testing options. 3) Describe the current state of genotype/phenotype correlations
      for CFTR mutations and an approach to interpreting both novel and previously
      described variants. 4) Provide a framework for genetic counselors to assist
      clients' decision-making regarding CF carrier testing, prenatal diagnosis, and
      pregnancy management. Disclaimer The practice guidelines of the National Society
      of Genetic Counselors (NSGC) are developed by members of the NSGC to assist
      genetic counselors and other health care providers in making decisions about
      appropriate management of genetic concerns; including access to and/or delivery
      of services. Each practice guideline focuses on a clinical or practice-based
      issue, and is the result of a review and analysis of current professional
      literature believed to be reliable. As such, information and recommendations
      within the NSGC practice guidelines reflect the current scientific and clinical
      knowledge at the time of publication, are only current as of their publication
      date, and are subject to change without notice as advances emerge.In addition,
      variations in practice, which take into account the needs of the individual
      patient and the resources and limitations unique to the institution or type of
      practice, may warrant approaches, treatments and/or procedures that differ from
      the recommendations outlined in this guideline. Therefore, these recommendations
      should not be construed as dictating an exclusive course of management, nor does
      the use of such recommendations guarantee a particular outcome. Genetic
      counseling practice guidelines are never intended to displace a health care
      provider's best medical judgment based on the clinical circumstances of a
      particular patient or patient population.Practice guidelines are published by
      NSGC for educational and informational purposes only, and NSGC does not "approve"
      or "endorse" any specific methods, practices, or sources of information.

PMID- 24014131
TI  - Pretransplant peritoneal dialysis relative to hemodialysis improves long-term
      survival of kidney transplant patients: a single-center observational study.
AB  - BACKGROUND: Kidney transplantation is the best option for the treatment of end
      stage renal disease in terms of survival and quality of life. These results can
      be influenced by the pretransplant dialysis modality. The aim of this study was
      to evaluate whether the pretransplantation dialysis modality influences patient
      and allograft survival beyond 10 years and examine the potential risk factors
      associated with the outcomes. METHODS: We conducted an observational,
      retrospective, single-center clinical study that included 236 patients [118
      undergoing peritoneal dialysis (PD) and 118 undergoing hemodialysis (HD)] who
      proceeded to transplantation during the period December 1990-2002. Donor and
      recipient data were collected from our hospital's clinical registries. The follow
      up period extended to the patient's death, the loss of the allograft, or loss to
      follow-up. The end date of the study was set at March 2012. RESULTS: In the
      multivariate analysis, the long-term patient survival rate was higher for the PD
      group than for the HD group [HR = 2.62 (1.01-6.8); p = 0.04]; however, the
      allograft survival rate was not significantly different between the two groups
      [HR = 0.68 (0.41-1.10); p = 0.12]. CONCLUSION: Pretransplantation dialysis
      modality is associated with long-term patient survival, with outcomes favoring
      peritoneal dialysis over hemodialysis. However, the pretransplant dialysis
      modality does not influence long-term graft loss risk.

PMID- 24014132
TI  - A prospective study comparing bipolar endoscopic enucleation of prostate with
      bipolar transurethral resection in saline for management of symptomatic benign
      prostate enlargement larger than 70 g in a matched cohort.
AB  - PURPOSE: This study aims to compare the efficacy and safety of bipolar endoscopic
      enucleation of prostate with transurethral resection in saline for large BPE
      greater than 70 g. METHODS: All patients from two urology centres who had bipolar
      enucleation or bipolar resection performed for large BPE greater than 70 g from
      December 2008 to April 2012 were prospectively assessed. The pre-operative and
      post-operative measures included IPSS, QOL score, uroflowmetry results, PSA and
      prostate volume. The perioperative measures were compared, and the post-operative
      complications/resumption of medical treatment for lower urinary tract symptoms
      were also assessed. RESULTS: There were 74 and 86 consecutive patients with
      bipolar enucleation and bipolar resection performed, respectively. No difference
      in pre-operative characteristics was observed between the two groups with mean
      prostate size 115 cc in each group. Comparing bipolar enucleation with bipolar
      resection, there was longer operative time (156 vs 87 min, p = 0.000), more
      haemoglobin drop (1.8 vs 1.1 g/dL, p = 0.006), but more prostate tissue resected
      (61.4 vs 45.7 g, p = 0.000). There was no difference in overall transfusion
      requirement and hospital stay. At 12 month after the procedure, patients with
      bipolar enucleation performed had better IPSS (6.4 vs 11.6, p = 0.032), QOL (1.7
      vs 2.6, p = 0.040) and peak flow rate (19.5 vs 15.1 ml/s, p = 0.019). The post
      operative complications had no significant difference between the two groups.
      CONCLUSIONS: For surgical treatment of big BPE, bipolar endoscopic enucleation of
      prostate provided superior functional outcome than bipolar resection but required
      longer operative time.

PMID- 24014133
TI  - The effects of preoperative immunosuppressive therapy on ischemia and reperfusion
      (I/R) injury in healthy rats.
AB  - PURPOSE: Warm-ischemia-induced injuries might be encountered during renal
      transplants from cadavers and healthy donors. Toll-like receptors (TLR) in
      ischemia-reperfusion (I/R) injury are one of the indicators of intracellular
      injury pathways. The intensity of ischemic injury is directly proportionate to
      high TLR levels. To minimize the I/R injury, we investigated TLR2 and TLR4 levels
      on rats, which were pretreated with tacrolimus (FK506) before I/R. METHODS: Eight
      Wistar albino rats in the study group were administered .01 mg/kg intramuscular
      tacrolimus. Administration to the study group was performed 24 and 1 h before
      warm ischemia. Eight rats in the control group were injected with 0.1 c.c. of
      distilled water. Blood samples were collected from the tail veins of all the rats
      on the first, second and third days. Expression levels of TLR2 and TLR4 genes
      were analyzed using the polymerase chain reaction method, to determine any
      significant difference between the control and study groups on the days when
      blood was taken. RESULTS: TLR2 (p = 0.045) and TLR4 (p = 0.022) levels in the
      study group were found to be statistically, and significantly, lower than those
      in the control group, on the second day following warm-ischemia- and reperfusion
      induced injury. CONCLUSIONS: Administration of immunosuppressive drugs to healthy
      donor rats led to a statistically significant reduction in the expression levels
      of TLR2 and TLR4 in the early period. In light of the data obtained by this
      study, we hypothesize that a preoperative therapy on donors might have a role in
      preventing I/R injury.

PMID- 24014134
TI  - Safety and efficacy of teneligliptin: a novel DPP-4 inhibitor for hemodialysis
      patients with type 2 diabetes.
AB  - PURPOSE: Teneligliptin is a novel DPP-4 inhibitor in development for treating
      type 2 diabetes mellitus that does not require dose adjustment for diabetic
      patients with end-stage renal disease; however, it had not been known whether or
      not teneligliptin is safe or potent in dialysis patients. We conducted a
      prospective study to assess the utility of teneligliptin for diabetic patients
      undergoing hemodialysis. METHODS: Blood glucose, glycated albumin, and HbA1c were
      measured every 4 weeks, at 4, 12, 20, and 28 weeks, and every 8 weeks,
      respectively, for patients treated with teneligliptin (n = 14; 7 patients newly
      started and 7 that switched from other medications) and patients of a control
      group who continued ongoing antidiabetic therapy (n = 29). RESULTS: Blood glucose
      level showed a 36.7 mg/dl decrease from 4 weeks in the teneligliptin group (p <
      0.05). The differences in glycated albumin (at 28 w) and HbA1c (at 24 w) between
      the teneligliptin group and the control group were -3.1 % (p < 0.05) and -0.57 %
      (p = 0.057), respectively. These parameters also decreased in patients who
      switched from voglibose 0.2 mg t.i.d. or vildagliptin 50 mg qd after
      teneligliptin administration. No case with hypoglycemia was identified. One
      patient had the dose of a laxative administered for constipation increased;
      however, no patient ceased teneligliptin due to side effects. CONCLUSION:
      Teneligliptin 20 mg is well tolerated, safe, and significantly improves glycemic
      control in diabetic patients with end-stage renal disease. Teneligliptin 20 mg
      once daily was considered to be more potent than voglibose 0.2 mg t.i.d. or
      vildagliptin 50 mg qd.

PMID- 24014135
TI  - One-Pot Synthesis of Multifunctional Polymers by Light-Controlled Radical
      Polymerization and Enzymatic Catalysis with Candida antarctica Lipase B.
AB  - The preparation of multifunctional polymers and block copolymers by a
      straightforward one-pot reaction process that combines enzymatic transacylation
      with light-controlled polymerization is described. Functional methacrylate
      monomers are synthesized by enzymatic transacylation and used in situ for light
      controlled polymerization, leading to multifunctional methacrylate-based polymers
      with well-defined microstructure. 

PMID- 24014136
TI  - Investigating the effect of the London living wage on the psychological wellbeing
      of low-wage service sector employees: a feasibility study.
AB  - BACKGROUND: Working poverty has become a major public health concern in recent
      times, and low-paid, insecure employment has been widely linked to poor
      psychological wellbeing. The London Living Wage (LLW) campaign aims to ensure
      employees receive adequate pay. The objective of this study is to investigate
      whether working for a LLW employer predicted higher levels of psychological
      wellbeing among low-wage service sector employees. METHODS: Workplace interviews
      were conducted with 300 service sector employees in London; 173 of whom were in
      LLW workplaces. Positive psychological wellbeing was measured using the Warwick
      Edinburgh Mental Wellbeing Scale. Multivariate linear regression was used to
      assess whether working for a LLW employer was associated with greater
      psychological wellbeing, adjusting for hypothesised confounding and mediating
      factors. RESULTS: After adjustment, respondents working for LLW employers had
      wellbeing scores 3.9 units higher on average than those who did not (95% CI: 1.8,
      6.0). These empirical results are complemented by methodological findings
      regarding the difficulties associated with accessing the study group.
      CONCLUSIONS: Those who worked for a LLW employer had significantly higher
      psychological wellbeing on average than those who did not. This was shown to be
      irrespective of any differences in the socioeconomic or demographic composition
      of these two groups.

PMID- 24014137
TI  - The value of impulsivity to define subgroups of addicted individuals differing in
      personality dysfunction, craving, psychosocial adjustment, and wellbeing: a
      latent class analysis.
AB  - High impulsivity is common to substance and gambling addictions. Despite these
      commonalities, there is still substantial heterogeneity on impulsivity levels
      within these diagnostic groups, and variations in impulsive levels predict higher
      severity of symptoms and poorer outcomes. We addressed the question of whether
      impulsivity scores can yield empirically driven subgroups of addicted individuals
      that will exhibit different clinical presentations and outcomes. We applied
      latent class analysis (LCA) to trait (UPPS-P impulsive behavior scale) and
      cognitive impulsivity (Stroop and d2 tests) scores in three predominantly male
      addiction diagnostic groups: Cocaine with Personality Disorders, Cocaine Non
      comorbid, and Gambling and analyzed the usefulness of the resulting subgroups to
      differentiate personality beliefs and relevant outcomes: Craving, psychosocial
      adjustment, and quality of life. In accordance with impulsivity scores, the three
      addiction diagnostic groups are best represented as two separate classes: Class 1
      characterized by greater trait impulsivity and poorer cognitive impulsivity
      performance and Class 2 characterized by lower trait impulsivity and better
      cognitive impulsivity performance. The two empirically derived classes showed
      significant differences on personality features and outcome variables (Class 1
      exhibited greater personality dysfunction and worse clinical outcomes), whereas
      conventional diagnostic groups showed non-significant differences on most of
      these measures. Trait and cognitive impulsivity scores differentiate subgroups of
      addicted individuals with more versus less severe personality features and
      clinical outcomes.

PMID- 24014139
TI  - Glycine insertion makes yellow fluorescent protein sensitive to hydrostatic
      pressure.
AB  - Fluorescent protein-based indicators for intracellular environment conditions
      such as pH and ion concentrations are commonly used to study the status and
      dynamics of living cells. Despite being an important factor in many biological
      processes, the development of an indicator for the physicochemical state of
      water, such as pressure, viscosity and temperature, however, has been neglected.
      We here found a novel mutation that dramatically enhances the pressure dependency
      of the yellow fluorescent protein (YFP) by inserting several glycines into it.
      The crystal structure of the mutant showed that the tyrosine near the chromophore
      flipped toward the outside of the beta-can structure, resulting in the entry of a
      few water molecules near the chromophore. In response to changes in hydrostatic
      pressure, a spectrum shift and an intensity change of the fluorescence were
      observed. By measuring the fluorescence of the YFP mutant, we succeeded in
      measuring the intracellular pressure change in living cell. This study shows a
      new strategy of design to engineer fluorescent protein indicators to sense
      hydrostatic pressure. 

PMID- 24014138
TI  - Wnt signaling in skeletal muscle dynamics: myogenesis, neuromuscular synapse and
      fibrosis.
AB  - The signaling pathways activated by Wnt ligands are related to a wide range of
      critical cell functions, such as cell division, migration, and synaptogenesis.
      Here, we summarize compelling evidence on the role of Wnt signaling on several
      features of skeletal muscle physiology. We briefly review the role of Wnt
      pathways on the formation of muscle fibers during prenatal and postnatal
      myogenesis, highlighting its role on the activation of stem cells of the adult
      muscles. We also discuss how Wnt signaling regulates the precise formation of
      neuromuscular synapses, by modulating the differentiation of presynaptic and
      postsynaptic components, particularly regarding the clustering of acetylcholine
      receptors on the muscle membrane. In addition, based on previous evidence showing
      that Wnt pathways are linked to several diseases, such as Alzheimer's and cancer,
      we address recent studies indicating that Wnt signaling plays a key role in
      skeletal muscle fibrosis, a disease characterized by an increase in the
      extracellular matrix components leading to failure in muscle regeneration, tissue
      disorganization and loss of muscle activity. In this context, we also discuss the
      possible cross-talk between the Wnt/beta-catenin pathway with two other critical
      profibrotic pathways, transforming growth factor beta and connective tissue
      growth factor, which are potent stimulators of the accumulation of connective
      tissue, an effect characteristic of the fibrotic condition. As it has emerged in
      other pathological conditions, we suggests that muscle fibrosis may be a
      consequence of alterations of Wnt signaling activity. 

PMID- 24014142
TI  - The effect of lisdexamfetamine dimesylate on body weight, metabolic parameters,
      and attention deficit hyperactivity disorder symptomatology in adults with
      bipolar I/II disorder.
AB  - OBJECTIVES: We primarily sought to determine the effect of adjunctive
      lisdexamfetamine dimesylate (LDX) on anthropometric and metabolic parameters. Our
      secondary aim was to evaluate the effect of LDX on attention deficit
      hyperactivity disorder (ADHD) symptom severity in adults with bipolar I/II
      disorder. METHODS: Forty-five stable adults (i.e., non-rapid cycling, absence of
      clinically significant hypo/manic symptoms) with bipolar I/II disorder and
      comorbid ADHD were enrolled in a phase IV, 4-week, flexible dose, open-label
      study of adjunctive LDX. All subjects were initiated at 30 mg/day of adjunctive
      LDX for the first week with flexible dosing (i.e., 30-70 mg/day) between weeks 2
      and 4. RESULTS: Of the 45 subjects enrolled, 40 received adjunctive LDX (mean
      dose = 60 +/- 10 mg/day). A statistically significant decrease from baseline to
      endpoint was evident in weight (p < 0.001), body mass index (p < 0.001), fasting
      total cholesterol (p = 0.011), low density lipoprotein cholesterol (p = 0.044),
      high density lipoprotein cholesterol (p = 0.015) but not triglycerides, or blood
      glucose. Significant reductions were also observed in leptin (p = 0.047), but not
      in ghrelin, adiponectin, or resistin levels. Diastolic blood pressure and pulse
      increased significantly over time but on average remained within the normal range
      (p < 0.001). There was a significant reduction from baseline to endpoint in the
      total score of the ADHD Self-Report Scale. Significant improvement from baseline
      to endpoint was also observed in the Montgomery-Asberg Depression Rating Scale
      total score as well as the Clinical Global Impression Severity and Improvement
      score. CONCLUSIONS: Short-term adjunctive LDX treatment was well tolerated by
      this sample of adults with stable bipolar I/II disorder. Lisdexamfetamine
      dimesylate offered beneficial effects on body weight, body mass index and several
      metabolic parameters. In addition to demonstrating short-term (i.e., 4 weeks)
      safety and tolerability, beneficial effects of LDX were also observed in
      mitigating depressive and ADHD symptom severity.

PMID- 24014141
TI  - Epidemiology and natural history of recovery of left ventricular function in
      recent onset dilated cardiomyopathies.
AB  - Although the long term prognosis of patients with dilated cardiomyopathy (DCM)
      remains poor, approximately 25 % of DCM patients with recent onset of heart
      failure (< 6 months) have a relatively benign clinical course with a
      spontaneously improvement in symptoms and partial, or in some cases complete,
      recovery of left ventricular (LV) function. Despite the longstanding recognition
      of the clinical phenomenon of LV recovery, relatively little attention has been
      paid to the etiology and natural history of this important group of DCM patients.
      Accordingly, in the present review we will focus on the epidemiology and natural
      history of recent onset DCM in patients who undergo spontaneous resolution of
      symptoms that is accompanied by recovery of LV function.

PMID- 24014140
TI  - Treatment strategies for the prevention of heart failure.
AB  - With the astounding morbidity and mortality associated with heart failure (HF),
      preventive approaches have been explored. Controlling hypertension to prevent HF
      is well-established, especially with sodium restriction and thiazide-based
      antihypertensive therapies showing potential advantages. Control of dyslipidemia
      with aggressive statin therapy is particularly beneficial in preventing HF in the
      setting of acute coronary syndrome. The HOPE study also established the benefit
      of ACE inhibitors in the prevention of HF in high-risk subjects. Meanwhile old
      data supporting tight glycemic control in preventing HF have not been confirmed,
      suggesting the complexity of diabetic cardiomyopathy. Avoiding tobacco use and
      other known cardiotoxins are likely helpful. While there has been substantial
      development in identifying biomarkers predicting future development of HF,
      therapeutic interdiction guided by biomarker levels have yet to be established,
      even though it offers hope in modulating the natural history of the development
      of HF in at-risk individuals. 

PMID- 24014143
TI  - Effect of food on the pharmacokinetics of lurasidone: results of two randomized,
      open-label, crossover studies.
AB  - OBJECTIVE: This study aimed to investigate the effect of prandial status and
      caloric and fat composition of meals on the pharmacokinetics of lurasidone.
      METHODS: Two randomized, open-label, crossover studies were conducted in
      clinically stable adults with schizophrenia or schizoaffective disorder. Study 1
      (n = 16) evaluated the effect of fasting and three meal types (100 kcal/medium
      fat, 200 kcal/medium fat, and 800-1000 kcal/high fat), and Study 2 (n = 26)
      evaluated the effect of fasting and five meal types (350 kcal/high fat, 500
      kcal/low fat, 500 kcal/high fat, 800-1000 kcal/low fat, and 800-1000 kcal/high
      fat) on the bioavailability of lurasidone. Subjects received lurasidone 120 mg
      once daily. Maximum serum concentration (Cmax ) and area under the serum
      concentration-time curve over the dosing interval (AUC0-tau ) were determined on
      Day 5 for each meal type. RESULTS: In Study 1, the geometric mean Cmax in the
      fasted state was 56.7 ng/mL compared with 123.0 ng/mL for the 800- to 1000-kcal
      meal; mean AUC0-tau was 360.0 versus 752.4 ng.h/mL (both p < 0.001). Lurasidone
      exposure following meals containing 100 and 200 kcal was substantially lower than
      with meals containing 800-1000 kcal. In Study 2, the geometric mean Cmax was 52.9
      ng/mL in the fasted state, 161 ng/mL for the 350-kcal/high-fat meal, 135 ng/mL
      for the 500-kcal/high-fat meal, and 131 ng/mL for the 800- to 1000-kcal/high-fat
      meal; mean AUC0-tau was 390, 743, 727, and 769 ng.h/mL, respectively. For all
      comparisons, the 90% confidence interval of the fed to fasted ratios indicated
      nonequivalence. Lurasidone exposure was similar following meals containing 350
      1000 kcal and was independent of fat content. CONCLUSION: Lurasidone should be
      administered with food-at least 350 kcal-to ensure maximum exposure.

PMID- 24014144
TI  - Longitudinal missing data strategies for substance use clinical trials using
      generalized estimating equations: an example with a buprenorphine trial.
AB  - OBJECTIVE: A review of substance use clinical trials indicates that sub-optimal
      methods are the most commonly used procedures to deal with longitudinal missing
      information. METHODS: Listwise deletion (i.e., using complete cases only),
      positive urine analysis (UA) imputation, and multiple imputation (MI) were used
      to evaluate the effect of baseline substance use and buprenorphine/naloxone
      tapering schedule (7 or 28 days) on the probability of a positive UA (UA+) across
      the 4-week treatment period. RESULTS: The listwise deletion generalized
      estimating equations (GEE) model demonstrated that those in the 28-day taper
      group were less likely to submit a UA+ for opioids during the treatment period
      (odds ratios (OR) = 0.57, 95% confidence interval (CI): 0.39-0.83), as did the
      positive UA imputation model (OR = 0.43, CI: 0.34-0.55). The MI model also
      demonstrated a similar effect of taper group (OR = 0.57, CI: 0.42-0.77), but the
      effect size was more similar to that of the listwise deletion model. CONCLUSIONS:
      Future researchers may find utilization of the MI procedure in conjunction with
      the common method of GEE analysis as a helpful analytic approach when the missing
      at random assumption is justifiable.

PMID- 24014145
TI  - Pharmacogenetic polymorphisms and response to escitalopram and venlafaxine over 8
      weeks in major depression.
AB  - OBJECTIVE: The objective of this study is to investigate the influence of the 5
      HTTLPR (serotonin transporter-linked promoter region), cytochrome P450 2C19, and
      cytochrome P450 2D6 polymorphisms on escitalopram (ESC) and venlafaxine (VEN)
      responses in major depressive disorder. METHOD: A prospective multi-site study of
      106 patients (Caucasian and Han Chinese ethnicities) with major depressive
      disorder treated with either ESC or VEN was conducted. The 17-item Hamilton
      Depression scale (HDRS), Clinical Global Impression Scale, and an adverse events
      scale (UKU) were assessed over 8 weeks, blind to genotype. RESULTS: At the 8-week
      end point, a significant HDRS reduction for both ESC and VEN occurred (p <
      0.0001). The 5-HTTLPR l/l genotype was associated with significantly greater
      score reductions on the HDRS compared with s/s carriers (p = 0.016) among
      Caucasian subjects receiving ESC (n = 47). Response rates were significantly
      higher for l/l (92%) compared with l/s (61%) and s/s (46%) variants (p = 0.042).
      For every l allele a participant carried, there was a 3.33 (95% confidence
      interval 1.25, 8.84; p = 0.02) times greater odds of ESC response. No significant
      associations between any of the genotypes and adverse effects were found.
      CONCLUSION: Ethnicity may have differential effects on the 5-HTTLPR genotype
      efficacy relationship. Results suggest that l/l allele for 5-HTTLPR is associated
      with a robust treatment response to ESC in Caucasian subjects only.

PMID- 24014147
TI  - Twenty-five-gauge vitrectomy versus 23-gauge vitrectomy in the management of
      macular diseases: a comparative analysis through a Health Technology Assessment
      model.
AB  - Small-gauge vitreoretinal techniques have been shown to be safe and effective in
      the management of a wide spectrum of vitreoretinal diseases. However, the costs
      of the new technologies may represent a critical issue for national health
      systems. The aim of the study is to plan a Health Technology Assessment (HTA) by
      performing a comparative analysis between the 23- and 25-gauge techniques in the
      management of macular diseases (epiretinal membranes, macular holes, vitreo
      macular traction syndrome). In this prospective study, 45-80-year-old patients
      undergoing vitrectomy surgery for macular disease were enrolled at the Torino Eye
      Hospital. In the HTA model we assessed the safety, clinical effectiveness, and
      cost and financial evaluation of 23-gauge compared with 25-gauge vitrectomies.
      Fifty patients entered the study; 14 patients underwent 23-gauge vitrectomy and
      36 underwent 25-gauge vitrectomy. There was no statistically significant
      difference in post-operative visual acuity at 1 year between the two groups. No
      cases of retinal detachment or endophtalmitis were registered at 1-year follow
      up. The 23-gauge technique was slightly more expensive than the 25-gauge: the
      total surgical costs were EUR1217.70 versus EUR1164.84 (p = 0.351). We provide a
      financial comparison between new vitreoretinal procedures recently introduced in
      the market and reimbursed by the Italian National Health System and we also
      stimulate a critical debate about the expensive technocratic model of medicine.

PMID- 24014148
TI  - Declining diversity in abandoned grasslands of the carpathian mountains: do
      dominant species matter?
AB  - Traditional haymaking has created exceptionally high levels of plant species
      diversity in semi-natural grasslands of the Carpathian Mountains (Romania), the
      maintenance of which is jeopardized by recent abandonment and subsequent
      vegetation succession. We tested the hypothesis that the different life history
      strategies of dominant grasses cause different patterns of diversity loss after
      abandonment of traditional haymaking in two types of meadow. Although diversity
      loss rate was not significantly different, the mechanism of loss depended on the
      life history of dominant species. In meadows co-dominated by competitive stress
      tolerant ruderals, diversity loss occurred following the suppression of dominant
      grasses by tall forbs, whereas in meadows dominated by a stress-tolerant
      competitor, diversity loss resulted from increased abundance and biomass of the
      dominant grass. We conclude that management for species conservation in abandoned
      grasslands should manipulate the functional turnover in communities where the
      dominant species is a weaker competitor, and abundance and biomass of dominant
      species in communities where the dominant species is the stronger competitor. 

PMID- 24014149
TI  - Studies for the enantiocontrolled preparation of substituted tetrahydropyrans:
      Applications for the synthesis of leucascandrolide A macrolactone.
AB  - Strategies for the stereocontrolled preparations of 2,6-cis-and 2,6-trans
      substituted tetrahydropyrans have been devised. These studies have explored
      methodology for asymmetric induction in SE' reactions using chiral 1,3,2
      diazaborolidine controllers. Reactions with aldehydes at -78  degrees C yield
      nonracemic 1,5-diols for chemoselective internal backside displacements. This
      concept is developed as a flexible and reliable strategy in studies toward
      leucascandrolide A macrolactone 2 via the sequential applications of SE'
      reactions leading to the C1-C9 aldehyde 14, and the bis-tetrahydropyran 59,
      respectively.

PMID- 24014150
TI  - Improved identification and relative quantification of sites of peptide and
      protein oxidation for hydroxyl radical footprinting.
AB  - Protein oxidation is typically associated with oxidative stress and aging and
      affects protein function in normal and pathological processes. Additionally,
      deliberate oxidative labeling is used to probe protein structure and protein
      ligand interactions in hydroxyl radical protein footprinting (HRPF). Oxidation
      often occurs at multiple sites, leading to mixtures of oxidation isomers that
      differ only by the site of modification. We utilized sets of synthetic, isomeric
      "oxidized" peptides to test and compare the ability of electron-transfer
      dissociation (ETD) and collision-induced dissociation (CID), as well as nano
      ultra high performance liquid chromatography (nanoUPLC) separation, to quantitate
      oxidation isomers with one oxidation at multiple adjacent sites in mixtures of
      peptides. Tandem mass spectrometry by ETD generates fragment ion ratios that
      accurately report on relative oxidative modification extent on specific sites,
      regardless of the charge state of the precursor ion. Conversely, CID was found to
      generate quantitative MS/MS product ions only at the higher precursor charge
      state. Oxidized isomers having multiple sites of oxidation in each of two peptide
      sequences in HRPF product of protein Robo-1 Ig1-2, a protein involved in nervous
      system axon guidance, were also identified and the oxidation extent at each
      residue was quantified by ETD without prior liquid chromatography (LC)
      separation. ETD has proven to be a reliable technique for simultaneous
      identification and relative quantification of a variety of functionally different
      oxidation isomers, and is a valuable tool for the study of oxidative stress, as
      well as for improving spatial resolution for HRPF studies. 

PMID- 24014151
TI  - Atmospheric pressure photo ionization hydrogen/deuterium exchange mass
      spectrometry--a method to differentiate isomers by mass spectrometry.
AB  - In this report, a method for in-source hydrogen/deuterium (H/D) exchange at
      atmospheric pressure is reported. The method was named atmospheric pressure photo
      ionization hydrogen/deuterium exchange mass spectrometry (APPI HDX MS). H/D
      exchange was performed by mixing samples dissolved in toluene with CH3OD solvent
      and analyzing the mixture using atmospheric pressure photo ionization mass
      spectrometry (APPI-MS). The APPI HDX spectra obtained with contact times between
      the analyte solution and methanol-OD (CH3OD) of < 0.5 s or 1 h showed the same
      pattern of H/D exchange. Therefore, it was concluded that APPI HDX occurred in
      the source but not in the solution. The proposed method does not require a
      specific type of mass spectrometer and can be performed at atmospheric pressure.
      H/D exchange can be performed in any laboratory with a mass spectrometer and a
      commercial APPI source. Using this method, multiple H/D exchanges of aromatic
      hydrogen and/or H/D exchange of active hydrogen were observed. These results
      demonstrated that H/D exchange can be used to distinguish between isomers
      containing primary, secondary, and tertiary amines, as well as pyridine and
      pyrrole functional groups.

PMID- 24014152
TI  - Practical aspects of recruitment and retention in clinical trials of rare genetic
      diseases: the phenylketonuria (PKU) experience.
AB  - Bringing treatments for rare genetic diseases to patients requires clinical
      research. Despite increasing activism from patient support and advocacy groups to
      increase access to clinical research studies, connecting rare disease patients
      with the clinical research opportunities that may help them has proven
      challenging. Chief among these challenges are the low incidence of these diseases
      resulting in a very small pool of known patients with a particular disease,
      difficulty of diagnosing rare genetic diseases, logistical issues such as long
      distances to the nearest treatment center, and substantial disease burden leading
      to loss of independence. Using clinical studies of phenylketonuria as an example,
      this paper discusses how, based on the authors' collective experience,
      partnership among clinicians, patients, study coordinators, genetic counselors,
      dietitians, industry, patient support groups, and families can help overcome the
      challenges of recruiting and retaining patients in rare disease clinical trials.
      We discuss specific methods of collaboration, communication, and education as
      part of a long-term effort to build a community committed to advancing the
      medical care of patients with rare genetic diseases. By talking to patients and
      families regularly about research initiatives and taking steps to make study
      participation as easy as possible, rare disease clinic staff can help ensure
      adequate study enrollment and successful study completion. 

PMID- 24014153
TI  - Acceptability of telemedicine and other cancer genetic counseling models of
      service delivery in geographically remote settings.
AB  - This work examined acceptability of cancer genetic counseling models of service
      delivery among Maine residents at risk for hereditary cancer susceptibility
      disorders. Pre-counseling, participants ranked characteristics reflecting models
      of care from most to least important including: mode-of-communication (in-person
      versus telegenetics), provider level of training (genetic specialty versus some
      training/experience), delivery format (one-on-one versus group counseling), and
      location (local versus tertiary service requiring travel). Associations between
      models of care characteristic rankings and patient characteristics, including
      rural residence, perceived cancer risk, and perceived risk for a hereditary
      cancer risk susceptibility disorder were examined. A total of 149/300 (49.7%
      response rate) individuals from 11/16 Maine counties responded; 30.8% were from
      rural counties; 92.2% indicated that an important/the most important model of
      care characteristic is provider professional qualifications. Among other
      characteristics, 65.1% ranked one-on-one counseling as important/the most
      important. In-person and local counseling were ranked the two least important
      characteristics (51.8% and 52.1% important/the most important, respectively).
      Responses did not vary by patient characteristics with the exception of greater
      acceptance of group counseling among those at perceived high personal cancer
      risk. Cancer telegenetic services hold promise for access to expert providers in
      a one-on-one format for rurally remote clients.

PMID- 24014154
TI  - Climate change hotspots in the CMIP5 global climate model ensemble.
AB  - We use a statistical metric of multi-dimensional climate change to quantify the
      emergence of global climate change hotspots in the CMIP5 climate model ensemble.
      Our hotspot metric extends previous work through the inclusion of extreme
      seasonal temperature and precipitation, which exert critical influence on climate
      change impacts. The results identify areas of the Amazon, the Sahel and tropical
      West Africa, Indonesia, and the Tibetan Plateau as persistent regional climate
      change hotspots throughout the 21st century of the RCP8.5 and RCP4.5 forcing
      pathways. In addition, areas of southern Africa, the Mediterranean, the Arctic,
      and Central America/western North America also emerge as prominent regional
      climate change hotspots in response to intermediate and high levels of forcing.
      Comparisons of different periods of the two forcing pathways suggest that the
      pattern of aggregate change is fairly robust to the level of global warming below
      approximately 2 degrees C of global warming (relative to the late-20th-century
      baseline), but not at the higher levels of global warming that occur in the late
      21st-century period of the RCP8.5 pathway, with areas of southern Africa, the
      Mediterranean, and the Arctic exhibiting particular intensification of relative
      aggregate climate change in response to high levels of forcing. Although specific
      impacts will clearly be shaped by the interaction of climate change with human
      and biological vulnerabilities, our identification of climate change hotspots can
      help to inform mitigation and adaptation decisions by quantifying the rate,
      magnitude and causes of the aggregate climate response in different parts of the
      world.

PMID- 24014156
TI  - Remote lung injury after experimental intestinal ischemia-reperfusion in horses.
AB  - Ischemia followed by reperfusion leads to release of toxic molecules into the
      circulation, and these molecules may cause injury in remote organs such as the
      lung. Horses commonly suffer from episodes of intestinal ischemia-reperfusion
      (IR) due to intestinal twisting/strangulation followed by repair. Because there
      is no evidence of lung injury associated with IR in horses, we designed a study
      to characterize the intestinal IR-associated lung inflammation and determine the
      effect of lidocaine on lung inflammation in IR horses. Lung tissues were
      collected from non-anesthetized (n=4) and anesthetized (n=4) control horses and
      horses (n=12) after 70 minutes of ischemia followed by 60 minutes of reperfusion.
      Horses in IR groups received Lactated Ringer's Solution (LRS; n=6) or lidocaine
      (n=6) intravenously. Control lungs had normal histology but lungs from IR horses
      showed moderate accumulation of neutrophils in blood vessels and airways. We
      found increased staining for TLR4, IL-8, TLR9, and von Willebrand factor (vWF)
      along with aggregates of vWF-positive platelets in lung vessels of IR horses
      compared to the controls. Lung TNFalpha was significantly increased in IR horses
      compared to the control horses (P<0.05). Neutrophil numbers, but not MPO
      concentrations, were significantly lower, while macrophage numbers were higher in
      the IR group receiving lidocaine compared to the LRS horses (P<0.05). We conclude
      that intestinal IR leads to remote lung injury characterized by recruitment of
      inflammatory cells and expression of inflammatory molecules in horses, and
      lidocaine may ameliorate lung inflammation following intestinal IR.

PMID- 24014155
TI  - Geriatric Traumatic Brain Injury in China.
AB  - Traumatic brain injury (TBI) is one of the major causes of morbidity and
      mortality in China. The elderly population has the higher rates of TBI-related
      hospitalization and death. Traffic accidents are the major cause for TBI in all
      age groups except in the group of 75 years and older, in which stumbles occurred
      in nearly half of those who suffered TBI. Older age is known to negatively
      influence outcome after TBI. To date, investigators have identified a panel of
      prognostic factors that include initial Glasgow Coma Scale score, comorbidities,
      cerebrospinal fluid leakage, associated extracranial lesions, and other factors
      such as cerebral perfusion pressure on recovery after injury. However, these
      aspects remain understudied in elderly patients with TBI. In the absence of
      complete clinical data, predicting outcomes and providing good care of the
      elderly population with TBI remain limited. To address this significant public
      health issue, a refocusing of research efforts is justified to prevent TBI in
      this population and to develop unique care strategies for achieving better
      clinical outcomes of the patients with TBI.

PMID- 24014157
TI  - Nod-like receptor protein 1 inflammasome mediates neuron injury under high
      glucose.
AB  - Diabetic encephalopathy is one of the most common complications of diabetes.
      Inflammatory events during diabetes may be an important mechanism of diabetic
      encephalopathy. Inflammasome is a multiprotein complex consisting of Nod-like
      receptor proteins (NLRPs), apoptosis-associated speck-like protein (ASC), and
      caspase 1 or 5, which functions to switch on the inflammatory process and the
      release of inflammatory factors. The present study hypothesized that the
      formation and activation of NLRP1 inflammasome turns on neuroinflammation and
      neuron injury during hyperglycemia. The results demonstrated that the levels of
      interleukin-1 beta (IL-1beta) were increased in the cortex of streptozocin (STZ)
      induced diabetic rats. The levels of mature IL-1beta and IL-18 were also elevated
      in culture medium of neurons treated with high glucose (50 mM). The expression of
      three essential components of the NLRP1 inflammasome complex, namely, NLRP1, ASC,
      and caspase 1, was also upregulated in vivo and in vitro under high glucose.
      Silencing the ASC gene prevented the caspase-1 activation, and inhibiting caspase
      1 activity blocked hyperglycemia-induced release of inflammatory factors and
      neuron injury. Moreover, we found that pannexin 1 mediated the actvitation of
      NLRP1 inflammasome under high glucose. These results suggest that hyperglycemia
      induces neuroinflammation through activation of NLRP1 inflammasome, which
      represents a novel mechanism of diabetes-associated neuron injury.

PMID- 24014159
TI  - Structure elucidation of host-guest complexes of tartaric and malic acids by
      quasi-racemic crystallography.
AB  - Racemic on the outside, but not inside: Aromatic-foldamer hosts are enantiomers
      and as such prefer to co-crystallize even though the guests (e.g. L-tartaric
      acid, see picture) in each host are not present as enantiomers. This behavior
      allows a one-step structure elucidation of diastereomeric and quasi-racemic
      structures in the solid state. 

PMID- 24014158
TI  - Modulation of Ca2+-currents by sequential and simultaneous activation of
      adenosine A1 and A 2A receptors in striatal projection neurons.
AB  - D(1)- and D(2)-types of dopamine receptors are located separately in direct and
      indirect pathway striatal projection neurons (dSPNs and iSPNs). In comparison,
      adenosine A(1)-type receptors are located in both neuron classes, and adenosine
      A(2A)-type receptors show a preferential expression in iSPNs. Due to their
      importance for neuronal excitability, Ca(2+)-currents have been used as final
      effectors to see the function of signaling cascades associated with different G
      protein-coupled receptors. For example, among many other actions, D(1)-type
      receptors increase, while D(2)-type receptors decrease neuronal excitability by
      either enhancing or reducing, respectively, CaV1 Ca(2+)-currents. These actions
      occur separately in dSPNs and iSPNs. In the case of purinergic signaling, the
      actions of A(1)- and A(2A)-receptors have not been compared observing their
      actions on Ca(2+)-channels of SPNs as final effectors. Our hypotheses are that
      modulation of Ca(2+)-currents by A(1)-receptors occurs in both dSPNs and iSPNs.
      In contrast, iSPNs would exhibit modulation by both A(1)- and A2A-receptors. We
      demonstrate that A(1)-type receptors reduced Ca(2+)-currents in all SPNs tested.
      However, A(2A)-type receptors enhanced Ca(2+)-currents only in half tested
      neurons. Intriguingly, to observe the actions of A(2A)-type receptors, occupation
      of A(1)-type receptors had to occur first. However, A(1)-receptors decreased
      Ca(V)2 Ca(2+)-currents, while A(2A)-type receptors enhanced current through
      Ca(V)1 channels. Because these channels have opposing actions on cell discharge,
      these differences explain in part why iSPNs may be more excitable than dSPNs. It
      is demonstrated that intrinsic voltage-gated currents expressed in SPNs are
      effectors of purinergic signaling that therefore play a role in excitability.

PMID- 24014160
TI  - Relation between parent psychiatric symptoms and youth problems: moderation
      through family structure and youth gender.
AB  - Links between parents' psychiatric symptoms and their children's behavioral and
      emotional problems have been widely documented in previous research, and the
      search for moderators of this association has begun. However, family structure
      (single versus dual-parent households) has received little attention as a
      potential moderator, despite indirect evidence that risk may be elevated in
      single-parent homes. Two other candidate moderators-youth gender and age-have
      been tested directly, but with inconsistent findings across studies, perhaps in
      part because studies have differed in whether they used youth clinical samples
      and in which informants (parents vs. youths) reported on youth problems. In the
      present study, we examined these three candidate moderators using a sample of
      exclusively clinic-referred youths (N = 333, 34 % girls, aged 7-14,) and
      assessing youth problems through both parent- and youth-reports. Both family
      structure and youth gender emerged as robust moderators across parent and youth
      informants. Parent symptoms were associated with youth internalizing and
      externalizing problems in single-parent but not dual-parent homes; and parent
      symptoms were associated with youth internalizing problems among boys, but not
      girls. The moderator findings suggest that the risks associated with parent
      psychopathology may not be uniform but may depend, in part, on family structure
      and youth gender.

PMID- 24014161
TI  - Adolescents' text message communication and growth in antisocial behavior across
      the first year of high school.
AB  - This study examined whether adolescents communicate about antisocial topics and
      behaviors via text messaging and how adolescents' antisocial text message
      communication relates to growth in rule-breaking and aggression as reported by
      youth, parents, and teachers. Participants (n = 172; 82 girls) received
      BlackBerry devices configured to capture all text messages sent and received.
      Four days of text messages during the 9th grade year were coded for discussion of
      antisocial activities. The majority of participants engaged in at least some
      antisocial text message communication. Text messaging about antisocial activities
      significantly predicted increases in parent, teacher, and self-reports of
      adolescents' rule-breaking behavior, as well as teacher and self-reports of
      adolescents' aggressive behavior. Text message communication may provide
      instrumental information about how to engage in antisocial behavior and reinforce
      these behaviors as normative within the peer group.

PMID- 24014163
TI  - The link between childhood exposure to violence and academic achievement: complex
      pathways.

PMID- 24014162
TI  - Early pubertal timing as a vulnerability to depression symptoms: differential
      effects of race and sex.
AB  - Robust evidence supports that girls and boys who experience early pubertal
      timing, maturing earlier than one's peers, are vulnerable to developing symptoms
      of depression. However, it has yet to be clarified whether early pubertal timing
      confers vulnerability to African American as well as to Caucasian adolescents and
      whether this vulnerability is specific to depressive symptoms or can be
      generalized to symptoms of social anxiety. In previous studies, one race or one
      sex was examined in isolation or sample sizes were too small to examine racial
      differences. Our longitudinal study consisted of a sample of 223 adolescents
      (Mage = 12.42, 54.3 % female, 50.2 % African American, and 49.8 % Caucasian). At
      baseline, depressive symptoms, social anxiety symptoms, and pubertal timing were
      assessed by self-report. Nine months later, we assessed depressive symptoms,
      social anxiety symptoms, body esteem, and stressful life events that occurred
      between baseline and follow-up. Analyses indicated that early pubertal timing
      interacted with stressful life events to predict increased symptoms of
      depression, but only for Caucasian girls and African American boys. Results were
      found to be specific to depressive symptoms and did not generalize to symptoms of
      social anxiety. Additionally, there was a significant positive indirect effect of
      pubertal timing on symptoms of depression through body esteem for Caucasian
      females. 

PMID- 24014164
TI  - Validation of the problem gambling severity index using confirmatory factor
      analysis and rasch modelling.
AB  - The Problem Gambling Severity Index (PGSI), a screening tool used to measure the
      severity of gambling problems in general population research, was subjected to
      confirmatory factor analysis and Rasch modelling to (a) confirm the one-factor
      structure; (b) assess how well the items measure the continuum of problem
      gambling severity; (c) identify sources of differential item functioning among
      relevant subpopulations of gamblers. Analyses were conducted on a nationally
      representative sample of over 25,000 gamblers compiled by merging data from the
      Canadian Community Health Survey and Canadian Problem Gambling Index (CPGI)
      integrated datasets. Results provided support for a one-factor model that was
      invariant across gender, age, income level, and gambler type. Rasch modelling
      revealed a well-fitting, unidimensional model with no miss-fitting items. The
      average severity assessed by the PGSI is consistent with moderately severe
      problem gambling. The PGSI is therefore weak in assessing low to moderate problem
      severity, a notable limitation of most brief gambling screens. Evidence of
      clinically significant differential item functioning was found with only one
      item, borrowing money to gamble, which behaved differently in gamblers who play
      electronic gaming machines or casino games compared to gamblers who avoid these
      games.

PMID- 24014166
TI  - Usefulness of parent-completed ASQ for neurodevelopmental screening of preterm
      children at five years of age.
AB  - INTRODUCTION: Preterm children are at greater risk of developmental impairment
      and require close follow-up for early and optimal medical care. Our goal was to
      examine use of the parent-completed Ages and Stages Questionnaire (ASQ) as a
      screening tool for neurodevelopmental disabilities in preterm infants at five
      years of age. PATIENTS AND METHODS: A total of 648 preterm children (<35 weeks
      gestational age) born between 2003 and 2004 and included in the regional Loire
      Infant Follow-up network were evaluated at five years of age. ASQ was compared
      with two validated tools (Intelligence Quotient and Global School Adaptation
      Score) and the impact of maternal education on the accuracy of this questionnaire
      was assessed. RESULTS: Overall ASQ scores for predicting full-scale IQ<85 and GSA
      score produced an area under the receiver operating characteristic curve of
      0.73+/-0.03 and 0.77+/-0.03, respectively. An ASQ cut-off value of 285 had
      optimal discriminatory power for identifying children with IQ scores<85 and GSA
      scores in the first quintile. ASQ values<285 were significantly associated with a
      higher risk of non-optimal neurologic outcomes (sensitivity of 0.80, specificity
      of 0.54 for IQ<85). ASQ values>285 were not distinctive for mild delay or normal
      development. In children with developmental delay, no difference was found when
      ASQ scores according to maternal education levels were analyzed. CONCLUSIONS: ASQ
      at five years is a simple and cost-effective tool that can detect severe
      developmental delay in preterm children regardless of maternal education level,
      while its capacity to identify children with mild delay appears to be more
      limited.

PMID- 24014167
TI  - Transitions between subclasses of bullying and victimization when entering middle
      school.
AB  - We examined the effects of depressive symptoms, antisocial attitudes, and
      perspective-taking empathy on patterns of bullying and victimization during the
      transition from late elementary (4th grade to 5th grade) to middle school (6th
      grade) among 1,077 students who participated in the Youth Matters (YM) bullying
      prevention trial. Latent transition analysis was used to establish classes of
      bullying, victimization, bully-victimization, and uninvolvement. The intervention
      had a positive impact on children as they moved from elementary to middle school.
      More students in the YM group transitioned from the involved statuses to the
      uninvolved status than students in the control group during the move to middle
      school. Elementary school bullies with higher levels of depressive symptoms were
      less likely than other students to move to an uninvolved status in the first year
      of middle school. Students who held greater antisocial attitudes were more likely
      to be a member of the bully-victim status than the uninvolved status during the
      move to middle school. Perspective-taking empathy, however, was not a significant
      predictor of status change during the transition to middle school. Implications
      for school-based prevention programs during the move to middle school are noted.

PMID- 24014168
TI  - Intentional forgetting: note-taking as a naturalistic example.
AB  - In the present study, we examined whether note-taking as a memory aid may provide
      a naturalistic example of intentional forgetting. In the first experiment,
      participants played Concentration, a memory card game in which the identity and
      location of pairs of cards need to be remembered. Before the game started, half
      of the participants were allowed to study the cards, and the other half made
      notes that were then unexpectedly taken away. No significant differences emerged
      between the two groups for remembering identity information, but the study group
      remembered significantly more location information than did the note-taking
      group. In a second experiment, we examined whether note-takers would show signs
      of proactive interference while playing Concentration repeatedly. The results
      indicated that they did not. The findings suggest that participants adopted an
      intentional-forgetting strategy when using notes to store certain types of
      information. 

PMID- 24014169
TI  - Structure-based gene targeting discovery of sphaerimicin, a bacterial translocase
      I inhibitor.
AB  - Rise and shine: Using a gene-targeting approach aimed at identifying potential L
      threonine:uridine-5'-transaldolases that catalyze the formation of (5'S,6'S)-C
      glycyluridine, a new bacterial translocase I inhibitor was discovered from an
      actinomycete following fermentation optimization. 

PMID- 24014165
TI  - Substance Abuse, Hepatitis C, and Aging in HIV: Common Cofactors that Contribute
      to Neurobehavioral Disturbances.
AB  - Although the prevalence of neurocognitive disturbances among individuals with HIV
      has decreased in recent years, rates of impairment still remain high. This review
      presents findings from comorbid conditions that may contribute to further
      neurocognitive impairments in this already vulnerable population. We will focus
      on three co-factors that have received substantial attention in the neuroAIDS
      literature: drug use, hepatitis C co-infection (HCV), and aging. All three
      conditions commonly co-occur with HIV and likely interact with HIV in complex
      ways. Collectively, the extant literature suggests that drug use, HCV, and aging
      serve to worsen the neurocognitive profile of HIV through several overlapping
      mechanisms. A better understanding of how specific comorbidities interact with
      HIV may reveal specific phenotypes of HIV-associated neurocognitive disorder that
      may aid in the development of more targeted behavioral and pharmacological
      treatment efforts.

PMID- 24014170
TI  - Interventions for managing relapse of the lower front teeth after orthodontic
      treatment.
AB  - BACKGROUND: Orthodontic relapse can be defined as the tendency for teeth to
      return to their pre-treatment position, and this occurs especially in lower front
      teeth (lower canines and lower incisors). Retention, to maintain the position of
      corrected teeth, has become one of the most important phases of orthodontic
      treatment. However, 10 years after the completion of orthodontic treatment, only
      30% to 50% of orthodontic patients effectively retain the satisfactory alignment
      initially obtained. After 20 years, satisfactory alignment reduces to 10%. When
      relapse occurs, simple effective strategies are required to effectively manage
      the problem. The periodontal, physiological or psychological conditions may be
      different from those before orthodontic treatment, so re-treatment methods may
      also need to be different. OBJECTIVES: To assess the effects of interventions
      used to manage relapse of the lower front teeth after first fixed orthodontic
      treatment. SEARCH METHODS: The following electronic databases were searched: the
      Cochrane Oral Health Group Trials Register (to 9 November 2012), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue
      10), MEDLINE via OVID (1950 to 9 November 2012), EMBASE via OVID (1980 to 9
      November 2012). There were no restrictions regarding language or date of
      publication. A thorough handsearch was done in relation to the following
      journals: American Journal of Orthodontics and Dentofacial Orthopedics (1970 to 9
      November 2012), Angle Orthodontist (1978 to 9 November 2012), European Journal of
      Orthodontics (1979 to 9 November 2012), Journal of Orthodontics (1978 to 9
      November 2012), Chinese Journal of Stomatology (1953 to 9 November 2012), West
      China Journal of Stomatology (1983 to 9 November 2012), Chinese Journal of Dental
      Materials and Devices (1992 to 9 November 2012) and Chinese Journal of
      Orthodontics (1994 to 9 November 2012). SELECTION CRITERIA: We would have
      included randomised controlled trials (RCTs) which compared any of the following:
      fixed options (including labial braces, lingual braces and fixed lingual wire),
      removable options (including Hawley's retainer with active components such as
      Hawley's retainer with spring elastomeric module, Bloore removable aligner and
      any other modifications on the Hawley's retainer to correct the lower front
      teeth, and invisible removable aligners such as Invisalign and Clearstep) and no
      active treatment for the management of relapsed lower front teeth after
      orthodontic treatment. We excluded RCTs of participants with craniofacial
      deformities/syndromes or serious skeletal deformities who received prior
      surgical/surgical orthodontic treatment. DATA COLLECTION AND ANALYSIS: Two review
      authors, independently and in duplicate, assessed the results of the searches to
      identify studies for inclusion. The Cochrane Collaboration statistical guidelines
      were to be followed for data synthesis. MAIN RESULTS: We did not identify any
      RCTs which met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: This
      review has revealed that there was no evidence from RCTs to show that one
      intervention was superior to another to manage the relapse of the alignment of
      lower front teeth using any method or index, aesthetic assessment by participants
      and practitioners, treatment time, patient's discomfort, quality of life, cost
      benefit considerations, stability of the correction, and side effects including
      pain, gingivitis, enamel decalcification and root resorption. There is an urgent
      need for RCTs in this area to identify the most effective and safe method for
      managing the relapse of alignment of the lower front teeth.

PMID- 24014172
TI  - Engaging with Lyell: Alfred Russel Wallace's Sarawak Law and Ternate papers as
      reactions to Charles Lyell's Principles of Geology.
AB  - Alfred Russel Wallace (1823-1913) and Charles Darwin (1809-1882) are honored as
      the founders of modern evolutionary biology. Accordingly, much attention has
      focused on their relationship, from their independent development of the
      principle of natural selection to the receipt by Darwin of Wallace's essay from
      Ternate in the spring of 1858, and the subsequent reading of the Wallace and
      Darwin papers at the Linnean Society on 1 July 1858. In the events of 1858
      Wallace and Darwin are typically seen as central players, with Darwin's friends
      Charles Lyell (1797-1875) and Joseph Dalton Hooker (1817-1911) playing supporting
      roles. This narrative has resulted in an under-appreciation of a more central
      role for Charles Lyell as both Wallace's inspiration and foil. The extensive anti
      transmutation arguments in Lyell's landmark Principles of Geology were taken as
      the definitive statement on the subject. Wallace, in his quest to solve the
      mystery of species origins, engaged with Lyell's arguments in his private field
      notebooks in a way that is concordant with his engagement with Lyell in the 1855
      and 1858 papers. I show that Lyell was the object of Wallace's Sarawak Law and
      Ternate papers through a consideration of the circumstances that led Wallace to
      send his Ternate paper to Darwin, together with an analysis of the material that
      Wallace drew upon from the Principles. In this view Darwin was, ironically,
      intended for a supporting role in mediating Wallace's attempted dialog with
      Lyell. 

PMID- 24014173
TI  - Charles Robert Darwin and Alfred Russel Wallace: their dispute over the units of
      selection.
AB  - Charles Darwin and Alfred Russel Wallace independently discovered the mechanism
      of natural selection for evolutionary change. However, they viewed the working of
      selection differently. For Darwin, selection was always focused on the benefit
      for the individual. For Wallace, selection was as much something of benefit for
      the group as for the individual. This difference is traced to their different
      background political-economic views, with Darwin in favor of Adam Smith's view of
      society and Wallace following Robert Owen in being a socialist. 

PMID- 24014171
TI  - Ordered disorder of the astrocytic dystrophin-associated protein complex in the
      norm and pathology.
AB  - The abundance and potential functional roles of intrinsically disordered regions
      in aquaporin-4, Kir4.1, a dystrophin isoforms Dp71, alpha-1 syntrophin, and alpha
      dystrobrevin; i.e., proteins constituting the functional core of the astrocytic
      dystrophin-associated protein complex (DAPC), are analyzed by a wealth of
      computational tools. The correlation between protein intrinsic disorder, single
      nucleotide polymorphisms (SNPs) and protein function is also studied together
      with the peculiarities of structural and functional conservation of these
      proteins. Our study revealed that the DAPC members are typical hybrid proteins
      that contain both ordered and intrinsically disordered regions. Both ordered and
      disordered regions are important for the stabilization of this complex. Many
      disordered binding regions of these five proteins are highly conserved among
      vertebrates. Conserved eukaryotic linear motifs and molecular recognition
      features found in the disordered regions of five protein constituting DAPC likely
      enhance protein-protein interactions that are required for the cellular functions
      of this complex. Curiously, the disorder-based binding regions are rarely
      affected by SNPs suggesting that these regions are crucial for the biological
      functions of their corresponding proteins. 

PMID- 24014174
TI  - Improving question-asking initiations in young children with autism using pivotal
      response treatment.
AB  - Social initiations make up a core deficit for children with autism spectrum
      disorder (ASD). In particular, initiated questions during social interactions are
      often minimal or absent in this population. In the context of a multiple baseline
      design, the efficacy of using the motivational procedures of Pivotal Response
      Treatment to increase social question-asking for three young children with autism
      was assessed. Results indicated that participants initiated a greater number of
      targeted questions following intervention. Additionally, all children exhibited
      increases in initiation of untargeted questions during social interaction in
      novel settings. Furthermore, post intervention data revealed collateral gains in
      communication and adaptive behavior. Theoretical implications of incorporating
      motivational strategies into intervention to improve social initiations in young
      children with ASD are discussed. 

PMID- 24014175
TI  - Traumatic Brain Injury in the Elderly: Is it as Bad as we Think?
AB  - Traumatic brain injury in elderly patients is a neglected global disease burden.
      The main cause is fall, followed by motor vehicle accidents. This review article
      summarizes different aspects of geriatric traumatic brain injury, including
      epidemiology, pathology, and effects of comorbidities and pre-injury medications
      such as antiplatelets and anticoagulants. Functional outcome with or without
      surgical intervention, cognitive outcome, and psychiatric complications are
      discussed. Animal models are also reviewed in attempt to explain the relationship
      of aging and outcome, together with advances in stem cell research. Though
      elderly people in general did fare worse after traumatic brain injury, certain
      "younger elderly" people, aged 65-75 years, could have a comparable outcome to
      younger adults after minor to moderate head injury.

PMID- 24014176
TI  - Characterization of thalamo-cortical association using amplitude and connectivity
      of functional MRI in mild traumatic brain injury.
AB  - PURPOSE: To examine thalamic and cortical injuries using fractional amplitude of
      low-frequency fluctuations (fALFFs) and functional connectivity MRI (fcMRI) based
      on resting state (RS) and task-related fMRI in patients with mild traumatic brain
      injury (MTBI). MATERIALS AND METHODS: Twenty-seven patients and 27 age-matched
      controls were recruited. The 3 Tesla fMRI at RS and finger tapping task were used
      to assess fALFF and fcMRI patterns. fALFFs were computed with filtering (0.01
      0.08 Hz) and scaling after preprocessing. fcMRI was performed using a standard
      seed-based correlation method, and delayed fcMRI (coherence) in frequency domain
      were also performed between thalamus and cortex. RESULTS: In comparison with
      controls, MTBI patients exhibited significantly decreased fALFFs in the thalamus
      (and frontal/temporal subsegments) and cortical frontal and temporal lobes; as
      well as decreased thalamo-thalamo and thalamo-frontal/ thalamo-temporal fcMRI at
      rest based on RS-fMRI (corrected P < 0.05). This thalamic and cortical disruption
      also existed at task-related condition in patients. CONCLUSION: The decreased
      fALFFs (i.e., lower neuronal activity) in the thalamus and its segments provide
      additional evidence of thalamic injury in patients with MTBI. Our findings of
      fALFFs and fcMRI changes during motor task and resting state may offer insights
      into the underlying cause and primary location of disrupted thalamo-cortical
      networks after MTBI.

PMID- 24014178
TI  - The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) induces mitochondrial and nuclear DNA damage in Caenorhabditis elegans.
AB  - The metabolites of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) form DNA adducts in animal models. While there are many
      reports of formation of nuclear DNA adducts, one report also detected NNK-induced
      damage to the mitochondrial genome in rats. Using a different DNA damage
      detection technology, we tested whether this finding could be repeated in the
      nematode Caenorhabditis elegans. We treated N2 strain (wild-type) nematodes with
      NNK in liquid culture, and applied quantitative PCR to analyze NNK-induced
      nuclear and mitochondrial DNA (mtDNA) damage. Our results confirm that NNK causes
      both nuclear and mtDNA damage. However, we did not detect a difference in the
      level of nuclear versus mtDNA damage in C. elegans. To test whether the mtDNA
      damage was associated with mitochondrial dysfunction, we used a transgenic
      nematode strain that permits in vivo measurement of ATP levels and found lower
      levels of ATP in NNK-exposed animals when compared with the unexposed controls.
      To test whether the lower levels of ATP could be attributed to inhibition of
      respiratory chain components, we investigated oxygen consumption in whole C.
      elegans and found reduced oxygen consumption in exposed animals when compared
      with the unexposed controls. Our data suggest a model in which NNK exposure
      causes damage to both C. elegans nuclear and mitochondrial genomes, and support
      the hypothesis that the mitochondrial damage is functionally important in this
      model. These results also represent a first step in developing this genetically
      tractable organism as a model for assessing NNK toxicity.

PMID- 24014177
TI  - Non-lyme tick-borne diseases: a neurological perspective.
AB  - Tick-borne diseases are prevalent throughout the world and present a diagnostic
      challenge owing to their nonspecific clinical symptoms. Many tick-borne diseases
      involve the central and peripheral nervous systems. Early diagnosis or at least
      suspicion of a tick-borne cause is necessary to institute early empiric
      treatment. After a brief review of tick biology, we present the most common tick
      borne diseases. A brief discussion of epidemiology, the transmission route, and
      pathogenesis is followed by a discussion of the clinical manifestations,
      diagnosis and treatment options when available. The review emphasizes the
      infectious causes with a significant neurological manifestation.

PMID- 24014180
TI  - The Rey Auditory Verbal Learning Test: normative data developed for the
      Venezuelan population.
AB  - The Rey Auditory Verbal Learning Test (RAVLT) is a neuropsychological tool widely
      used to assess functions such as attention, memory, and learning ability in the
      auditory-verbal domain. Norms for the test have been developed in many different
      languages and they show different relationships with demographic variables. The
      main objective of this research was to develop specific norms for the Venezuelan
      population, with particular focus on the influences of age, education, gender,
      and socioeconomic status. A Spanish version of the test was administered to a
      quota sample of 629 healthy adults. Pearson's correlation analysis (p < .001)
      showed a significant association between RAVLT performance and age (r = -.401),
      education (r = .386), and socioeconomic status (r = -.196), but not between RAVLT
      performance and gender (r = -.054). Due to the strength of the correlations, only
      age and education were considered in the development of final norms. 

PMID- 24014179
TI  - Theoretical approach towards increasing effectiveness of palatal surgery in
      obstructive sleep apnea: role for concomitant positional therapy?
AB  - PURPOSE: The aims of this study are to evaluate the effect of palatal surgery
      (uvulopalatopharyngoplasty (UPPP) or Z-palatoplasty (ZPP)) with or without (+/-)
      concomitant radiofrequent ablation of the base of the tongue (RFTB) on body
      position-specific apnea-hypopnea index (AHI) values in patients with obstructive
      sleep apnea (OSA) and to compare this treatment outcome to the theoretical effect
      of (addition of) positional therapy (PT). METHODS: Retrospective analysis of pre-
      and posttreatment polysomnographies in 139 patients who had undergone UPPP/ZPP +/
      RFTB was performed. Hypothetical evaluation of the effects of (addition of)
      ideal PT on AHI in positional OSA (POSA) patients was carried out. RESULTS:
      Median AHI significantly decreased from 18.0 to 11.2 (p < 0.001). Median AHI in
      all separate positions decreased significantly as well. Sixty-eight patients
      suffered from POSA and showed a significant decrease in median AHI from 15.5 to
      11.5 (p = 0.002). In the 71 non-positional OSA (NPOSA) patients, the significant
      AHI decrease was more outspoken, from 23.0 to 11.0 (p < 0.001). Our hypothetical
      model to treat POSA patients with an ideal PT (as monotherapy or in addition to
      surgery) resulted in a significant median AHI decrease from 18.0 to 4.5 (p <
      0.0001). CONCLUSIONS: UPPP/ZPP +/- RFTB significantly reduces AHI and all body
      position-specific AHI values. This reduction is significantly higher in NPOSA
      than in POSA patients. When considering UPPP/ZPP +/- RFTB, the effect of body
      position needs to be taken into account. PT, either as monotherapy or in addition
      to surgery, theoretically has shown to improve treatment results dramatically in
      POSA patients. Prospective, controlled trials focusing on the effects of this
      combination of treatments should further evaluate this hypothetical conclusion.

PMID- 24014181
TI  - Exporting poor health: the Irish in England.
AB  - In the twentieth century, the Irish-born population in England has typically been
      in worse health than both the native population and the Irish population in
      Ireland, a reversal of the commonly observed healthy migrant effect. Recent birth
      cohorts living in England and born in Ireland, however, are healthier than the
      English population. The substantial Irish migrant health penalty arises
      principally for cohorts born between 1920 and 1960. In this article, we attempt
      to understand the processes that generated these changing migrant health patterns
      for Irish migrants to England. Our results suggest a strong role for economic
      selection in driving the dynamics of health differences between Irish-born
      migrants and white English populations. 

PMID- 24014182
TI  - Big microdata for population research.
AB  - This article describes an explosion in the availability of individual-level
      population data. By 2018, demographic researchers will have access to over 2
      billion records of accessible microdata from over 100 countries, dating from 1703
      to the present. Another 2 to 4 billion records will be available through
      restricted-access data enclaves. These new resources represent a new kind of data
      that will enable transformative research on demographic and economic change and
      the spatial organization of society.

PMID- 24014183
TI  - Selection of specific protein binders for pre-defined targets from an optimized
      library of artificial helicoidal repeat proteins (alphaRep).
AB  - We previously designed a new family of artificial proteins named alphaRep based
      on a subgroup of thermostable helicoidal HEAT-like repeats. We have now assembled
      a large optimized alphaRep library. In this library, the side chains at each
      variable position are not fully randomized but instead encoded by a distribution
      of codons based on the natural frequency of side chains of the natural repeats
      family. The library construction is based on a polymerization of micro-genes and
      therefore results in a distribution of proteins with a variable number of
      repeats. We improved the library construction process using a "filtration"
      procedure to retain only fully coding modules that were recombined to recreate
      sequence diversity. The final library named Lib2.1 contains 1.7*10(9) independent
      clones. Here, we used phage display to select, from the previously described
      library or from the new library, new specific alphaRep proteins binding to four
      different non-related predefined protein targets. Specific binders were selected
      in each case. The results show that binders with various sizes are selected
      including relatively long sequences, with up to 7 repeats. ITC-measured
      affinities vary with Kd values ranging from micromolar to nanomolar ranges. The
      formation of complexes is associated with a significant thermal stabilization of
      the bound target protein. The crystal structures of two complexes between
      alphaRep and their cognate targets were solved and show that the new interfaces
      are established by the variable surfaces of the repeated modules, as well by the
      variable N-cap residues. These results suggest that alphaRep library is a new and
      versatile source of tight and specific binding proteins with favorable
      biophysical properties. 

PMID- 24014185
TI  - Incidentally detected hepatocellular carcinoma in cirrhotic children.

PMID- 24014184
TI  - Precocious puberty--perspectives on diagnosis and management.
AB  - The term 'precocious puberty' signifies the onset of secondary sexual characters
      before the age of 9 y in boys and 8 y in girls. Menarche before 9.5 y is also
      considered precocious. These definitions are constantly evolving due to the
      secular trends observed all over the world. It is crucial to decide whether the
      child has central (gonadotropin-dependent, GDPP) or peripheral (gonadotropin
      independent, GIPP) form of precocious puberty. Some benign conditions such as
      premature thelarche and premature pubarche may mimic precocious puberty. A
      systematic approach with detailed history and clinical examination helps to
      arrive at a diagnosis in most cases. An underlying neurologic disorder is more
      likely in a very young boy. Basal LH level is the best screening test to diagnose
      GDPP. LH level less than 0.1 IU/L by a very sensitive assay indicates prepubertal
      stage. Stimulation tests using gonadotropin releasing hormone (GnRH) or its
      analog (GnRHa), leuprolide help to confirm the diagnosis of GDPP. High resolution
      MRI of brain helps to detect abnormalities in hypothalamus and pituitary region.
      GnRH analogs (GnRHa) are the only effective treatment for GDPP at present. In
      girls, breast size may regress; menses ceases and vaginal mucosa becomes non
      estrogenized. In boys testicular volumes remain static or decrease and genital
      growth regresses. The effects of GnRH analogs are reversible on discontinuation
      of therapy, with restoration of normal function within 3 mo after stopping
      treatment. Treatment of GIPP however is far from satisfactory. 

PMID- 24014186
TI  - Pharmacokinetics of lopinavir determined with an ELISA test in youths with
      perinatally acquired HIV.
AB  - OBJECTIVE: To investigate the plasma levels of lopinavir by enzyme-linked
      immunosorbent assay (ELISA) in a cohort of patients who were vertically infected
      with human immunodeficiency virus 1 (HIV). METHODS: Plasma levels of lopinavir
      (Cmin) were determined by ELISA test in patients treated with lopinavir/ritonavir
      based combined antiretroviral therapy who had achieved virological response after
      4 wk of therapy. Reference lopinavir concentrations were Cmin 1-8 MUg/mL.
      Correlation between lopinavir plasma concentration and continuous variables was
      evaluated by mean of Pearson correlation coefficient. Differences in lopinavir
      (LPV) concentration for binary categorical variables were assessed by Mann
      Whitney test, while for variables with more than two categories Kruskal-Wallis
      test was used. RESULTS: Thirty-four patients were enrolled; median age was 133 mo
      (15-265). The median lopinavir dose tested was 383.5 mg/kg (IQR: 266.6-400
      mg/kg), with a median plasma concentration of 8.8 MUg/mL (IQR: 5-14 MUg/mL).
      Lopinavir Cmin was <1 MUg/mL in only one sample (2.9 %), while 14 samples had
      Cmin between 1 and 8 MUg/mL (41.2 %) and 19 (55.9 %) > 8 MUg/mL. No significant
      correlations were found between plasma concentrations of lopinavir and the
      continuous variables considered in the study. A negative but, not completely
      significant, correlation was found between plasma drug concentration and body
      mass index (r = -0.29; p = 0.09). CONCLUSIONS: The use of a simple and relatively
      cost-effective methodology might render therapeutic drug monitoring (TDM) appeal
      in the daily clinical practice.

PMID- 24014187
TI  - Bronchiolitis obliterans associated with Stevens-Johnson syndrome and response to
      azathioprine.

PMID- 24014188
TI  - Occurrence of the synthetic analgesic tramadol in an African medicinal plant.

PMID- 24014189
TI  - Multi-Source Learning for Joint Analysis of Incomplete Multi-Modality
      Neuroimaging Data.
AB  - Incomplete data present serious problems when integrating largescale brain
      imaging data sets from different imaging modalities. In the Alzheimer's Disease
      Neuroimaging Initiative (ADNI), for example, over half of the subjects lack
      cerebrospinal fluid (CSF) measurements; an independent half of the subjects do
      not have fluorodeoxyglucose positron emission tomography (FDG-PET) scans; many
      lack proteomics measurements. Traditionally, subjects with missing measures are
      discarded, resulting in a severe loss of available information. We address this
      problem by proposing two novel learning methods where all the samples (with at
      least one available data source) can be used. In the first method, we divide our
      samples according to the availability of data sources, and we learn shared sets
      of features with state-of-the-art sparse learning methods. Our second method
      learns a base classifier for each data source independently, based on which we
      represent each source using a single column of prediction scores; we then
      estimate the missing prediction scores, which, combined with the existing
      prediction scores, are used to build a multi-source fusion model. To illustrate
      the proposed approaches, we classify patients from the ADNI study into groups
      with Alzheimer's disease (AD), mild cognitive impairment (MCI) and normal
      controls, based on the multi-modality data. At baseline, ADNI's 780 participants
      (172 AD, 397 MCI, 211 Normal), have at least one of four data types: magnetic
      resonance imaging (MRI), FDG-PET, CSF and proteomics. These data are used to test
      our algorithms. Comprehensive experiments show that our proposed methods yield
      stable and promising results.

PMID- 24014190
TI  - Health status, perceptions and needs of Hispanics in rural Shelbyville, Kentucky.
AB  - This cross-sectional study was completed to characterize the health status,
      perceptions and needs of Hispanics in Shelbyville, KY, USA. Community Health
      Workers interviewed 668 Hispanic residents in Shelbyville, KY, USA. Data were
      collected from 2009 to 2010 and analyzed from 2011 until present. Hispanic
      immigrants from Mexico and other Central American countries completed the survey.
      The most common self-reported diseases were allergies, asthma, diabetes, lung
      disease and cardiovascular disease. High blood pressure and diabetes were the two
      most common diagnoses among insured, older females. Health education, disease
      prevention and nutrition were the top health concerns among participants.
      Deficits in health care infrastructure for this largely transient community may
      compromise their ability to meet health care needs and concerns. Similar issues
      may be faced by other disadvantaged Hispanic communities in the continental US
      and likely to be influenced by anticipated provisions of the Patient Protection
      and Affordable Care Act. 

PMID- 24014191
TI  - Antibiotics for treating chronic osteomyelitis in adults.
AB  - BACKGROUND: Chronic osteomyelitis is generally treated with antibiotics and
      surgical debridement but can persist intermittently for years with frequent
      therapeutic failure or relapse. Despite advances in both antibiotic and surgical
      treatment, the long-term recurrence rate remains around 20%. This is an update of
      a Cochrane review first published in 2009. OBJECTIVES: To determine the effects
      of different systemic antibiotic treatment regimens for treating chronic
      osteomyelitis in adults. SEARCH METHODS: We searched the Cochrane Bone, Joint and
      Muscle Trauma Group Specialised Register (October 2012), the Cochrane Central
      Register of Controlled Trials (The Cochrane Library 2012, Issue 9), MEDLINE
      (January 1948 to September Week 4 2012), EMBASE (January 1980 to 2012 Week 40),
      LILACS (October 2012), the WHO International Clinical Trials Registry Platform
      (June 2012) and reference lists of relevant articles. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) or quasi-RCTs addressing the effects of
      different antibiotic treatments given after surgical debridement for chronic
      osteomyelitis in adults. DATA COLLECTION AND ANALYSIS: Two review authors
      independently screened papers for inclusion, extracted data and appraised risk of
      bias in the included trials. Where appropriate, we pooled data using the fixed
      effect model. MAIN RESULTS: We included eight small trials involving a total of
      282 participants with chronic osteomyelitis. Data were available from 248
      participants. Most participants were male with post-traumatic osteomyelitis,
      usually affecting the tibia and femur, where recorded. The antibiotic regimens,
      duration of treatment and follow-up varied between trials. All trials mentioned
      surgical debridement before starting on antibiotic therapy as part of treatment,
      but it was unclear in four trials whether all participants underwent surgical
      debridement.We found that study quality and reporting were often inadequate. In
      particular, we judged almost all trials to be at moderate to high risk of bias
      due to failure to conceal allocation and inadequate follow-up.Four trials
      compared oral versus parenteral route for administration of antibiotics. There
      was no statistically significant difference between the two groups in the
      remission at the end of treatment (70/80 versus 58/70; risk ratio (RR) 1.04, 95%
      confidence interval (CI) 0.92 to 1.18; four trials, 150 participants). There was
      no statistically significant difference between the two groups in the remission
      rate 12 or more months after treatment (49/64 versus 44/54; RR 0.94, 95% CI 0.78
      to 1.13; three trials, 118 participants). There was also no significant
      difference between the two groups in the occurrence of mild adverse events (11/64
      versus 8/54; RR 1.08, 95% CI 0.49 to 2.42; three trials, 118 participants) or
      moderate and severe adverse events (3/49 versus 4/42; RR 0.69, 95% CI 0.19 to
      2.57; three trials, 91 participants). Superinfection occurred in participants of
      both groups (5/66 in the oral group versus 4/58 in the parenteral group; RR 1.08,
      95% CI 0.33 to 3.60; three trials, 124 participants).Single trials with few
      participants found no statistical significant differences for remission or
      adverse events for the following four comparisons: oral only versus parenteral
      plus oral administration; parenteral plus oral versus parenteral only
      administration; two different parenteral antibiotic regimens; and two different
      oral antibiotic regimens. No trials compared different durations of antibiotic
      treatment for chronic osteomyelitis, or adjusted the remission rate for bacteria
      species or severity of disease. AUTHORS' CONCLUSIONS: Limited and low quality
      evidence suggests that the route of antibiotic administration (oral versus
      parenteral) does not affect the rate of disease remission if the bacteria are
      susceptible to the antibiotic used. However, this and the lack of statistically
      significant differences in adverse effects need confirmation. No or insufficient
      evidence exists for other aspects of antibiotic therapy for chronic
      osteomyelitis.The majority of the included trials were conducted over 20 years
      ago and currently we are faced with a far higher prevalence of bacteria that are
      resistant to many of the available antibiotics used for healthcare. This
      continuously evolving bacterial resistance represents another challenge in the
      choice of antibiotics for treating chronic osteomyelitis.

PMID- 24014192
TI  - Sex differences in predictors of violent and non-violent juvenile offending.
AB  - In response to concerns regarding the rise in female juvenile violent crime and
      the dearth of gender-specific research, this study aimed to identify predictors
      of violent offending in female offenders. Data were extracted from risk
      assessments of 586 male and female juvenile offenders (aged 11-17 years)
      conducted between 2005 and 2009 by the Youth Offending Service in
      Gloucestershire, an English county. Information regarding the young people's
      living arrangements, family and personal relationships, education,
      emotional/mental health, thinking and behavior, and attitudes to offending was
      recorded. Comparisons were made between the violent male offenders (N = 185), the
      violent female offenders (N = 113), the non-violent male offenders (N = 150), and
      the non-violent female offenders (N = 138) for these variables. These were
      followed by a multinomial logistic regression analysis. The findings indicated
      that engaging in self-harm was the best predictor of being a female violent
      offender, with the predictors of giving into pressure from others and attempted
      suicide nearing significance. Furthermore, non-violent females were significantly
      less likely to lose control of their temper and more likely to give in to
      pressure from others than their violent counterparts. Non-violent males were
      significantly less likely to lose control of their temper and more likely to self
      harm and give in to pressure from others than violent males. Although many
      similarities existed between sexes for predictors of violent offending, the
      findings of this study indicate that more attention needs to be paid to the
      mental health of female offenders.

PMID- 24014193
TI  - Isolation and characterization of two satellite DNAs in some Iberian rock lizards
      (Squamata, Lacertidae).
AB  - Satellite DNAs represent a large portion of all high eukaryotic genomes. They
      consist of numerous very similar repeated sequences, tandemly arranged in large
      clusters up to 100 million base pairs in length, usually located in the
      heterochromatic parts of chromosomes. The biological significance of satDNAs is
      still under discussion, but most of their proposed functions are related to
      heterochromatin and/or centromere formation and function. Because information
      about the structure of reptilian satDNA is far from exhaustive, we present a
      molecular and cytogenetic characterization of two satDNA families in four
      lacertid species. Two families of tandemly repeated DNAs, namely TaqI and HindIII
      satDNAs, have been cloned and sequenced from four species belonging to the genus
      Iberolacerta. These satDNAs are characterized by a monomer length of 171-188 and
      170-172 bp, and by an AT content of 60.5% and 58.1%, respectively. FISH
      experiments with TaqI satDNA probe produced bright signals in pericentromeric
      regions of a subset of chromosomes whereas all the centromeres were marked by
      HindIII probe. The results obtained in this study suggest that chromosome
      location and abundance of satDNAs influence the evolution of these elements, with
      centromeric families evolving tenfold faster than interstitial/pericentromeric
      ones. Such different rates render different satellites useful for phylogenetic
      investigation at different taxonomic ranks.

PMID- 24014194
TI  - Can Robotic Interaction Improve Joint Attention Skills?
AB  - Although it has often been argued that clinical applications of advanced
      technology may hold promise for addressing impairments associated with autism
      spectrum disorder (ASD), relatively few investigations have indexed the impact of
      intervention and feedback approaches. This pilot study investigated the
      application of a novel robotic interaction system capable of administering and
      adjusting joint attention prompts to a small group (n = 6) of children with ASD.
      Across a series of four sessions, children improved in their ability to orient to
      prompts administered by the robotic system and continued to display strong
      attention toward the humanoid robot over time. The results highlight both
      potential benefits of robotic systems for directed intervention approaches as
      well as potent limitations of existing humanoid robotic platforms.

PMID- 24014195
TI  - Brief report: The use of self-report measures in young people with autism
      spectrum disorder to access symptoms of anxiety, depression and negative
      thoughts.
AB  - The aims of this study were two-fold; firstly, to investigate whether self-report
      measures are useful and reflect parent-reported psychiatric symptoms in children
      with autism spectrum disorder (ASD), and secondly, to investigate whether
      children with ASD are able to access and report their cognitions, a prerequisite
      skill for cognitive behavior therapies. Thirty children with ASD and 21
      comparison children without ASD completed the Spence Children's Anxiety Scale and
      the Children's Depression Inventory, with parents completing the parent version
      of both questionnaires. Intraclass correlations revealed that there was good
      agreement between ASD children and their parents on both measures, but only on
      the depression measure in non-ASD children. The children in both groups also
      completed the Children's Automatic Thoughts Questionnaires; multiple regression
      analyses indicated that within the ASD group, child-rated scores on the CATS
      questionnaire were positively related to increased self-reported symptoms of
      anxiety and depression, but not in the comparison group, suggesting that children
      with ASD are able to accurately report their anxious and depressed cognitions.
      The implications of these results for both the practice and theory of CBT for
      children with ASD are discussed. 

PMID- 24014197
TI  - National Bone Health Alliance: an innovative public-private partnership improving
      America's bone health.
AB  - The U.S. National Bone Health Alliance (NBHA) is a public-private partnership
      launched in 2010 that brings together its 56 partners from the government,
      nonprofit, and for-profit sectors to collectively promote bone health and prevent
      disease; improve bone disease diagnosis and treatment; and enhance bone research,
      surveillance, and evaluation. NBHA is driven to achieve its 20/20 vision to
      reduce fractures 20 % by the year 2020 through projects including 2Million2Many,
      an osteoporosis awareness campaign; Fracture Prevention CENTRAL, an online
      resource center providing support to sites interested in launching a secondary
      fracture prevention program; bone turnover marker standardization project; and
      working groups in rare bone disease and the clinical diagnosis of osteoporosis.
      NBHA provides a platform to coordinate messaging among individuals and
      organizations on subjects important to bone health; pool funding and efforts
      around shared priorities; and work together towards the goals and recommendations
      of the National Action Plan on Bone Health. 

PMID- 24014196
TI  - Reduction in retinal nerve fiber layer thickness in young adults with autism
      spectrum disorders.
AB  - Recent years have seen an increase in the use of retinal nerve fiber layer (RNFL)
      evaluation as an easy-to-use, reproducible, proxy-measure of brain structural
      abnormalities. Here, we evaluated RNFL thickness in a group of subjects with high
      functioning autism (HFA) or with Asperger Syndrome (AS) to its potential as a
      tool to study autism pathophysiology. All subjects underwent high-resolution
      spectral domain optical coherence tomography to evaluate RNFL thickness. HFA
      subjects presented with reduced global RNFL thickness compared both to AS
      subjects and controls. AS subjects showed a reduced nasal quadrant RNFL thickness
      compared to controls. Verbal-IQ/performance-IQ discrepancy correlated with RNFL
      thickness. Our data suggest that RNFL evaluation could help in the development of
      biological markers of autism pathophysiology. 

PMID- 24014198
TI  - Phytoscreening and phytoextraction of heavy metals at Danish polluted sites using
      willow and poplar trees.
AB  - The main purpose of this study was to determine typical concentrations of heavy
      metals (HM) in wood from willows and poplars, in order to test the feasibility of
      phytoscreening and phytoextraction of HM. Samples were taken from one strongly,
      one moderately, and one slightly polluted site and from three reference sites.
      Wood from both tree species had similar background concentrations at 0.5 mg kg(
      1) for cadmium (Cd), 1.6 mg kg(-1) for copper (Cu), 0.3 mg kg(-1) for nickel
      (Ni), and 25 mg kg(-1) for zinc (Zn). Concentrations of chromium (Cr) and lead
      (Pb) were below or close to detection limit. Concentrations in wood from the
      highly polluted site were significantly elevated, compared to references, in
      particular for willow. The conclusion from these results is that tree coring
      could be used successfully to identify strongly heavy metal-polluted soil for Cd,
      Cu, Ni, Zn, and that willow trees were superior to poplars, except when screening
      for Ni. Phytoextraction of HMs was quantified from measured concentration in wood
      at the most polluted site. Extraction efficiencies were best for willows and Cd,
      but below 0.5% over 10 years, and below 10/00 in 10 years for all other HMs.

PMID- 24014199
TI  - Behavior and mechanism of arsenate adsorption on activated natural siderite:
      evidences from FTIR and XANES analysis.
AB  - Activated natural siderite (ANS) was used to investigate its characteristics and
      mechanisms of As(V) adsorption from aqueous solution. Batch tests were carried
      out to determine effects of contact time, initial As(V) concentration,
      temperature, pH, background electrolyte, and coexisting anions on As(V)
      adsorption. Arsenic(V) adsorption on ANS well-fitted pseudo-second-order
      kinetics. ANS showed a high-adsorption capacity of 2.19 mg/g estimated from
      Langmuir isotherm at 25  degrees C. Thermodynamic studies indicated that As(V)
      adsorption on ANS was spontaneous, favorable, and endothermic. ANS adsorbed As(V)
      efficiently in a relatively wide pH range between 2.0 and 10.0, although the
      removal efficiency was slightly higher in acidic conditions than that in basic
      conditions. Effects of background electrolyte and coexisting anions were not
      significant within the concentration ranges observed in high As groundwater.
      Results of XRD and Fe K-edge XANES analysis suggested ANS acted as an
      Fe(II)/(III) hybrid system, which was quite effective in adsorbing As from
      aqueous solution. There was no As redox transformation during adsorption,
      although Fe(II) oxidation occurred in the system. Two infrared bands at 787 and
      872 cm(-1) after As(V) adsorption suggested that As(V) should be predominantly
      adsorbed on ANS via inner-sphere bidendate binuclear surface complexes.

PMID- 24014200
TI  - Heterogeneous Fenton oxidation of Direct Black G in dye effluent using functional
      kaolin-supported nanoscale zero iron.
AB  - This study investigated kaolin-supported nanoscale zero-valent iron (nZVI/K) as a
      heterogeneous Fenton-like catalyst for the adsorption and oxidation of an azo
      dye, Direct Black G (DBG). New findings suggest that kaolin as a support material
      not only reduced the aggregation of nanoscale zero-valent iron (nZVI) but also
      improved the adsorption of DBG. It consequently improved Fenton oxidation by
      increasing the local concentration of DBG in the vicinity of nZVI. This was
      confirmed by scanning electron microscopy and X-ray diffraction for the surface
      morphology of nZVI/K before and after the Fenton-like reaction. Furthermore,
      nZVI/K proved to be a catalyst for the heterogeneous Fenton-like oxidation of the
      DBG process in the neutral pH range. More than 87.22 % of DBG was degraded, and
      54.60 % of total organic carbon was removed in the optimal conditions: 0.6 g/L
      dosage of nZVI/K, 33 mM H2O2, 100 mg/L initial DBG concentration, temperature of
      303 K and pH of 7.06. Finally, it was demonstrated that nZVI/K removed DBG from
      dye wastewater through the processes of adsorption and oxidation.

PMID- 24014201
TI  - Feature Grouping and Selection Over an Undirected Graph.
AB  - High-dimensional regression/classification continues to be an important and
      challenging problem, especially when features are highly correlated. Feature
      selection, combined with additional structure information on the features has
      been considered to be promising in promoting regression/classification
      performance. Graph-guided fused lasso (GFlasso) has recently been proposed to
      facilitate feature selection and graph structure exploitation, when features
      exhibit certain graph structures. However, the formulation in GFlasso relies on
      pairwise sample correlations to perform feature grouping, which could introduce
      additional estimation bias. In this paper, we propose three new feature grouping
      and selection methods to resolve this issue. The first method employs a convex
      function to penalize the pairwise linfinity norm of connected
      regression/classification coefficients, achieving simultaneous feature grouping
      and selection. The second method improves the first one by utilizing a non-convex
      function to reduce the estimation bias. The third one is the extension of the
      second method using a truncated l1 regularization to further reduce the
      estimation bias. The proposed methods combine feature grouping and feature
      selection to enhance estimation accuracy. We employ the alternating direction
      method of multipliers (ADMM) and difference of convex functions (DC) programming
      to solve the proposed formulations. Our experimental results on synthetic data
      and two real datasets demonstrate the effectiveness of the proposed methods.

PMID- 24014202
TI  - Mutations in the EPHA2 gene are a major contributor to inherited cataracts in
      South-Eastern Australia.
AB  - Congenital cataract is the most common cause of treatable visual impairment in
      children worldwide. Mutations in many different genes lead to congenital
      cataract. Recently, mutations in the receptor tyrosine kinase gene, EPHA2, have
      been found to cause congenital cataract in six different families. Although these
      findings have established EPHA2 as a causative gene, the total contribution of
      mutations in this gene to congenital cataract is unknown. In this study, for the
      first time, a population-based approach was used to investigate the frequency of
      disease causing mutations in the EPHA2 gene in inherited cataract cases in South
      Eastern Australia. A cohort of 84 familial congenital or juvenile cataract index
      cases was screened for mutations in the EPHA2 gene by direct sequencing. Novel
      changes were assessed for segregation with the disease within the family and in
      unrelated controls. Microsatellite marker analysis was performed to establish any
      relationship between families carrying the same mutation. We report a novel
      congenital cataract causing mutation c.1751C>T in the EPHA2 gene and the
      previously reported splice mutation c.2826-9G>A in two new families.
      Additionally, we report a rare variant rs139787163 potentially associated with
      increased susceptibility to cataract. Thus mutations in EPHA2 account for 4.7% of
      inherited cataract cases in South-Eastern Australia. Interestingly, the
      identified rare variant provides a link between congenital and age-related
      cataract. 

PMID- 24014203
TI  - Letter to the Glycoforum: Improved protocols for preparing lipid-linked and
      related saccharides for Fluorophore-Assisted Carbohydrate Electrophoresis (FACE).

PMID- 24014205
TI  - Inspiratory muscle training for asthma.
AB  - BACKGROUND: In some people with asthma, expiratory airflow limitation, premature
      closure of small airways, activity of inspiratory muscles at the end of
      expiration and reduced pulmonary compliance may lead to lung hyperinflation. With
      the increase in lung volume, chest wall geometry is modified, shortening the
      inspiratory muscles and leaving them at a sub-optimal position in their length
      tension relationship. Thus, the capacity of these muscles to generate tension is
      reduced. An increase in cross-sectional area of the inspiratory muscles caused by
      hypertrophy could offset the functional weakening induced by hyperinflation.
      Previous studies have shown that inspiratory muscle training promotes diaphragm
      hypertrophy in healthy people and patients with chronic heart failure, and
      increases the proportion of type I fibres and the size of type II fibres of the
      external intercostal muscles in patients with chronic obstructive pulmonary
      disease. However, its effects on clinical outcomes in patients with asthma are
      unclear. OBJECTIVES: To evaluate the efficacy of inspiratory muscle training with
      either an external resistive device or threshold loading in people with asthma.
      SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of
      trials, Cochrane Central Register of Controlled Trials (CENTRAL),
      ClinicalTrials.gov and reference lists of included studies. The latest search was
      performed in November 2012. SELECTION CRITERIA: We included randomised controlled
      trials that involved the use of an external inspiratory muscle training device
      versus a control (sham or no inspiratory training device) in people with stable
      asthma. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures
      expected by The Cochrane Collaboration. MAIN RESULTS: We included five studies
      involving 113 adults. Participants in four studies had mild to moderate asthma
      and the fifth study included participants independent of their asthma severity.
      There were substantial differences between the studies, including the training
      protocol, duration of training sessions (10 to 30 minutes) and duration of the
      intervention (3 to 25 weeks). Three clinical trials were produced by the same
      research group. Risk of bias in the included studies was difficult to ascertain
      accurately due to poor reporting of methods.The included studies showed a
      statistically significant increase in inspiratory muscle strength, measured by
      maximal inspiratory pressure (PImax) (mean difference (MD) 13.34 cmH2O, 95% CI
      4.70 to 21.98, 4 studies, 84 participants, low quality evidence). Our other
      primary outcome, exacerbations requiring a course of oral or inhaled
      corticosteroids or emergency department visits, was not reported. For the
      secondary outcomes, results from one trial showed no statistically significant
      difference between the inspiratory muscle training group and the control group
      for maximal expiratory pressure, peak expiratory flow rate, forced expiratory
      volume in one second, forced vital capacity, sensation of dyspnoea and use of
      beta2-agonist. There were no studies describing inspiratory muscle endurance,
      hospital admissions or days off work or school. AUTHORS' CONCLUSIONS: There is no
      conclusive evidence in this review to support or refute inspiratory muscle
      training for asthma. The evidence was limited by the small number of trials with
      few participants together with the risk of bias. More well conducted randomised
      controlled trials are needed. Future trials should investigate the following
      outcomes: lung function, exacerbation rate, asthma symptoms, hospital admissions,
      use of medications and days off work or school. Inspiratory muscle training
      should also be assessed in people with more severe asthma and conducted in
      children with asthma.

PMID- 24014206
TI  - Development and validation of Trivandrum Development Screening Chart for children
      aged 0-6 years [TDSC (0-6)].
AB  - OBJECTIVE: To develop and validate a simple screening tool for identifying
      developmental delay among children of 0-6 y of age in the community. METHODS: The
      51-items of Trivandrum Development Screening Chart for children of 0-6 y [TDSC (0
      6 y)], were carefully prepared from the norms in various existing developmental
      charts/scales, by experts keeping in mind the face validity and content validity.
      The criterion validity was assessed in a community sample of 1,183 children of 0
      6 y with a mean age of 35.38 mo (SD of 19.25) including 597 (50.46%) boys and 586
      (49.54%) girls. TDSC (0-6 y) was validated against Denver Developmental Screening
      Test (DDST) as the 'Reference Standard'. RESULTS: When one item delay in TDSC (0
      6 y) was considered as 'TDSC delay' (test positive), the sensitivity and
      specificity of TDSC (0-6 y) was found to be 84.62% (95% CI: 71.92-93.12) and
      90.8% (95% CI: 88.97-92.43) respectively with a Negative Predictive Value of
      99.23% (95% CI: 98.48-99.67) and LR (negative) of 0.17(95% CI: 0.09-0.32). The
      test-retest and inter-rater reliability [an interclass correlation (ICC) of 0.77
      for test-retest and ICC of 0.97 for inter-rater] were good and acceptable.
      CONCLUSIONS: TDSC (0-6 y) is a simple, reliable and valid screening tool for use
      in the community to identify children between 0 and 6 y with developmental delay,
      enabling early intervention practices.

PMID- 24014207
TI  - Microglia in normal appearing white matter of multiple sclerosis are alerted but
      immunosuppressed.
AB  - Little is known about the functional phenotype of microglia in normal appearing
      white matter (NAWM) of multiple sclerosis (MS), although it may hold valuable
      clues about mechanisms for lesion development. Therefore, we studied microglia
      from NAWM obtained post-mortem from controls (n = 25) and MS patients (n = 21)
      for their phenotype ex vivo and their immune responsiveness in vitro, using a
      microglia isolation method that omits culture and adherence. By flow cytometry,
      microglia in MS NAWM displayed elevated CD45 levels and increased size and
      granularity but were distinct from autologous choroid plexus macrophages by
      absent or low expression of additional markers, in particular CD206. Flow
      cytometric analysis of microglia from NAWM of three controls and four MS patients
      showed alterations in levels of Fc-gamma receptors in MS. In primary microglia
      from a bigger sample of subjects, analysis of Fc-gamma receptors by quantitative
      PCR indicated a significant increase in mRNA levels of the inhibitory CD32b
      isoform in MS NAWM. Despite their changed activation status, microglia from MS
      NAWM were unresponsive to lipopolysaccharide in vitro. Notably, culture with
      dexamethasone led to an impaired induction of the inflammation-limiting cytokine
      CCL18 in microglia from MS NAWM compared with those from control NAWM. Together,
      these data demonstrate that microglia in MS NAWM are in an alerted state, but
      display features of immunosuppression. Thus, the activation status of microglia
      in NAWM of MS patients likely reflects a response to ongoing neuroinflammation,
      which coincides with upregulation of immunoregulatory molecules to prevent full
      activation and damage to the vulnerable milieu.

PMID- 24014208
TI  - Pharmacokinetics and safety of the sesame lignans, sesamin and episesamin, in
      healthy subjects.
AB  - A single-blind, placebo-controlled, parallel-group and multiple oral dose study
      was conducted in 48 healthy subjects to investigate the pharmacokinetics and
      safety of multiple oral doses of sesame lignans (sesamin and episesamin).
      Subjects were randomly divided into two groups. Each subject was administered 50
      mg of sesame lignans (sesamin/episesamin=1/1) or placebo once daily for 28 days.
      The pharmacokinetics of the sesame lignans were investigated using 10 of the 24
      subjects in the sesame lignans group. No serious adverse events were observed in
      this study. Sesamin was absorbed with a peak plasma concentration at 5.0 h. The
      plasma concentration of the main metabolite, SC-1, reached a peak at 5.0 h and
      decreased rapidly with a terminal half-life of 2.4 h. Episesamin was also
      absorbed with a peak plasma concentration at 5.0 h and decreased with a terminal
      half-life of 7.1 h. The plasma concentration of the main metabolite, EC-1,
      reached a peak at 5.0 h and decreased rapidly with a terminal half-life of 3.4 h.
      The plasma concentrations of sesamin and episesamin reached a steady state by day
      7. Sesame lignans were confirmed to be safe and tolerable in healthy subjects.
      The results of the pharmacokinetic study demonstrate that no accumulation was
      observed following multiple 50 mg doses of sesame lignans.

PMID- 24014209
TI  - Teaching with comics: a course for fourth-year medical students.
AB  - Though graphic narratives (or comics) now permeate popular culture, address every
      conceivable topic including illness and dying, and are used in educational
      settings from grade school through university, they have not typically been
      integrated into the medical school curriculum. This paper describes a popular and
      innovative course on comics and medicine for 4th-year medical students. In this
      course, students learn to critically read book length comics as well as create
      their own stories using the comics format. The rationale for the course, its
      general content and format, and methods for teaching are described. Finally, the
      author offers some reflections on why this medium resonates so powerfully with
      medical student learners. 

PMID- 24014211
TI  - Probing lateral charge transport in single molecule layers: how charge is
      transported over long distances in fullerene self-assembled monolayers.

PMID- 24014212
TI  - Laser acupuncture in the treatment of burning mouth syndrome: a pilot study.

PMID- 24014213
TI  - Simultaneously enhancing spectral resolution and sensitivity in heteronuclear
      correlation NMR spectroscopy.
AB  - BIRD's eye view: Adding periodic BIRD J-refocusing (BIRD=bilinear rotation
      decoupling) to data acquisition in an HSQC experiment causes broadband
      homonuclear decoupling, giving a single signal for each proton chemical shift.
      This pure shift method improves both resolution and signal-to-noise ratio,
      without the need for special data processing. 

PMID- 24014215
TI  - Live birth rates and birth outcomes by diagnosis using linked cycles from the
      SART CORS database.
AB  - PURPOSE: This study uses linked cycles of assisted reproductive technology (ART)
      to examine cumulative live birth rates, birthweight, and length of gestation by
      diagnostic category. METHODS: We studied 145,660 women with 235,985 ART cycles
      reported to the Society for Assisted Reproductive Technology Clinic Outcomes
      Reporting System during 2004-2010. ART cycles were linked to individual women by
      name, date of birth, social security number, partner's name, and sequence of ART
      treatments. The study population included the first four autologous oocyte cycles
      for women with a single diagnosis of male factor, endometriosis, ovulation
      disorders, diminished ovarian reserve, or unexplained infertility. Live birth
      rates were calculated per cycle, per cycle number (1-4), and cumulatively.
      Birthweight and length of gestation were calculated for singleton births.
      RESULTS: Within each diagnosis, live birth rates were highest in the first cycle
      and declined with successive cycles. Women with diminished ovarian reserve had
      the lowest live birth rate (cumulative rate of 28.3 %); the live birth rate for
      the other diagnoses were very similar (cumulative rates from 62.1 % to 65.7 %).
      Singleton birthweights and lengths of gestation did not differ substantially
      across diagnoses, ranging from 3,112 to 3,286 g and 265 to 270 days,
      respectively. These outcomes were comparable with national averages for singleton
      births in the United States (3,296 g and 271 days). CONCLUSION: Women with the
      diagnosis of diminished ovarian reserve had substantially lower live birth rates.
      However, singleton birthweights and lengths of gestation outcomes were similar
      across all other diagnoses.

PMID- 24014216
TI  - Effects of mammalian herbivore declines on plant communities: observations and
      experiments in an African savanna.
AB  - 1. Herbivores influence the structure and composition of terrestrial plant
      communities. However, responses of plant communities to herbivory are variable
      and depend on environmental conditions, herbivore identity and herbivore
      abundance. As anthropogenic impacts continue to drive large declines in wild
      herbivores, understanding the context dependence of herbivore impacts on plant
      communities becomes increasingly important. 2. Exclosure experiments are
      frequently used to assess how ecosystems reorganize in the face of large wild
      herbivore defaunation. Yet in many landscapes, declines in large wildlife are
      often accompanied by other anthropogenic activities, especially land conversion
      to livestock production. In such cases, exclosure experiments may not reflect
      typical outcomes of human-driven extirpations of wild herbivores. 3. Here, we
      examine how plant community responses to changes in the identity and abundance of
      large herbivores interact with abiotic factors (rainfall and soil properties). We
      also explore how effects of wild herbivores on plant communities differ between
      large-scale herbivore exclosures and landscape sites where anthropogenic activity
      has caused wildlife declines, often accompanied by livestock increases. 4.
      Abiotic context modulated the responses of plant communities to herbivore
      declines with stronger effect sizes in lower-productivity environments. Also,
      shifts in plant community structure, composition and species richness following
      wildlife declines differed considerably between exclosure experiments and
      landscape sites in which wild herbivores had declined and were often replaced by
      livestock. Plant communities in low wildlife landscape sites were distinct in
      both composition and physical structure from both exclosure and control sites in
      experiments. The power of environmental (soil and rainfall) gradients in
      influencing plant response to herbivores was also greatly dampened or absent in
      the landscape sites. One likely explanation for these observed differences is the
      compensatory effect of livestock associated with the depression or extirpation of
      wildlife. 5.Synthesis. Our results emphasize the importance of abiotic
      environmental heterogeneity in modulating the effects of mammalian herbivory on
      plant communities and the importance of such covariation in understanding effects
      of wild herbivore declines. They also suggest caution when extrapolating results
      from exclosure experiments to predict the consequences of defaunation as it
      proceeds in the Anthropocene.

PMID- 24014214
TI  - Clomiphene citrate co-treatment with low dose urinary FSH versus urinary FSH for
      clomiphene resistant PCOS: randomized controlled trial.
AB  - PURPOSE: The aim of this study was to examine the effect of clomiphene citrate
      [CC] co-administration during the use of exogenous low-dose urinary FSH [uFSH]
      for induction of ovulation in CC-resistant infertile PCOS women. METHODS: In a
      randomised controlled setting, 174 CC-resistant infertile PCOS women were
      randomized into two parallel groups; Group I received CC 100 mg/day for 5 days
      plus uFSH 37.5 IU/day while group II received only uFSH 37.5 IU /day. Subsequent
      increments of uFSH by 37.5 IU/day were made according to response. Primary
      outcome was ovulation rate. Secondary outcomes were clinical pregnancy rates,
      number of follicles, endometrial thickness, and gonadotropins consumption.
      RESULTS: Our results have demonstrated that group I compared to group II had
      significantly higher ovulation rate per intention to treat [ITT] [72.4 % vs. 34.2
      %, p < 0.001]. Clinical pregnancy and live birth rates were comparable between
      the two groups. Group I consumed significantly lower total FSH dose and needed
      significantly shorter stimulation duration compared to group II. CONCLUSION: CC
      co-administered during low dose HP uFSH versus uFSH for CC-resistant PCOS yields
      significantly higher ovulation rate and less consumption of FSH.

PMID- 24014217
TI  - Feasibility of transcatheter aortic valve implantation in systemic lupus
      erythematosus associated non-calcific aortic stenosis.

PMID- 24014218
TI  - Frequency of drug-induced valvular heart disease in patients previously exposd to
      benfluorex: a multicentre prospective study.
AB  - AIMS: The epidemiologic link between benfluorex use and an increased global
      frequency of left heart valve regurgitation has been well documented. However, no
      data linking previous drug exposure to the frequency of diagnosis of drug-induced
      valvular heart disease (DI-VHD) are available. The present study was conducted to
      address this issue. METHODS AND RESULTS: This echocardiography reader-blinded,
      controlled study conducted in 10 centres between February 2010 and February 2012
      prospectively included 835 subjects previously exposed to benfluorex referred by
      primary care physicians for echocardiography. Based on blinded off-line analysis,
      echocardiography findings were classified as: (i) DI-VHD+ for patients with an
      echocardiographic diagnosis of DI-VHD, (ii) inconclusive, and (iii) DI-VHD- for
      patients without signs of DI-VHD. Fifty-seven (6.8%) patients exposed to
      benfluorex were classified as DI-VHD+, 733 (87.8%) patients were classified as DI
      VHD-, and 45 (5.4%) were classified as inconclusive. Mitral and aortic DI-VHD
      were reported in 43 patients (5.1%) and 30 (3.6%) patients, respectively. Longer
      duration of exposure, female gender, smoking, and lower BMI were independently
      associated with a diagnosis of DI-VHD. Good inter-observer reproducibility was
      observed for the echocardiography classification (Kappa = 0.83, P < 0.00001).
      CONCLUSIONS: About 7% of patients without a history of heart valve disease
      previously exposed to benfluorex present echocardiography features of DI-VHD.
      Further studies are needed to study the natural history of DI-VHD and to identify
      risk factors for the development of drug-induced valve lesions.

PMID- 24014219
TI  - Repairs of an aortic root to right atrium iatrogenic fistula after unsuccessful
      percutaneous mitral valvuloplasty.

PMID- 24014220
TI  - Physical activity in patients with stable coronary heart disease: an
      international perspective.
AB  - AIMS: Despite the known benefits of regular exercise, the reasons why many
      coronary heart disease (CHD) patients engage in little physical activity are not
      well understood. This study identifies factors associated with low activity
      levels in individuals with chronic CHD participating in the STABILITY study, a
      global clinical outcomes trial evaluating the lipoprotein phospholipaseA2
      inhibitor darapladib. METHODS AND RESULTS: Prior to randomization, 15 486 (97.8%)
      participants from 39 countries completed a lifestyle questionnaire. Total
      physical activity was estimated from individual subject self-reports of hours
      spend each week on mild, moderate, and vigorous exercise, corresponding
      approximately to 2, 4, and 8 METS, respectively. Multivariate logistic regression
      evaluated clinical and demographic variables for the lowest compared with higher
      overall exercise levels, and for individuals who decreased rather than maintained
      or increased activity since diagnosis of CHD. The least active 5280 subjects
      (34%) reported exercise of <= 24 MET.h/week. A total of 7191 subjects (46%)
      reported less exercise compared with before diagnosis of CHD. The majority of
      participants were either 'not limited' or 'limited a little' walking 100 m (84%),
      climbing one flight of stairs (82%), or walking 1 km/1/2; mile (68%), and <10%
      were limited 'a lot' by dyspnoea or angina. Variables independently associated
      with both low physical activity and decreasing exercise after diagnosis of CHD
      included more co-morbid conditions, poorer general health, fewer years of
      education, race, and country (P < 0.001 for all). CONCLUSION: In this
      international study, low physical activity was only partly explained by
      cardiovascular symptoms. Potentially modifiable societal and health system
      factors are important determinants of physical inactivity in patients with
      chronic CHD.

PMID- 24014221
TI  - Cardiogenic shock from acute ST-segment elevation myocardial infarction induced
      by severe multivessel coronary vasospasm.

PMID- 24014222
TI  - The impact of climate change on the potential distribution of agricultural pests:
      the case of the coffee white stem borer (Monochamus leuconotus P.) in Zimbabwe.
AB  - The production of agricultural commodities faces increased risk of pests,
      diseases and other stresses due to climate change and variability. This study
      assesses the potential distribution of agricultural pests under projected
      climatic scenarios using evidence from the African coffee white stem borer (CWB),
      Monochamus leuconotus (Pascoe) (Coleoptera: Cerambycidae), an important pest of
      coffee in Zimbabwe. A species distribution modeling approach utilising Boosted
      Regression Trees (BRT) and Generalized Linear Models (GLM) was applied on current
      and projected climate data obtained from the WorldClim database and occurrence
      data (presence and absence) collected through on-farm biological surveys in
      Chipinge, Chimanimani, Mutare and Mutasa districts in Zimbabwe. Results from both
      the BRT and GLM indicate that precipitation-related variables are more important
      in determining species range for the CWB than temperature related variables. The
      CWB has extensive potential habitats in all coffee areas with Mutasa district
      having the largest model average area suitable for CWB under current and
      projected climatic conditions. Habitat ranges for CWB will increase under future
      climate scenarios for Chipinge, Chimanimani and Mutare districts while it will
      decrease in Mutasa district. The highest percentage change in area suitable for
      the CWB was for Chimanimani district with a model average of 49.1% (3 906 ha)
      increase in CWB range by 2080. The BRT and GLM predictions gave similar predicted
      ranges for Chipinge, Chimanimani and Mutasa districts compared to the high
      variation in current and projected habitat area for CWB in Mutare district. The
      study concludes that suitable area for CWB will increase significantly in
      Zimbabwe due to climate change and there is need to develop adaptation
      mechanisms. 

PMID- 24014223
TI  - Challenges in understanding the sources of bioaccumulated metals in biota
      inhabiting turbid river systems.
AB  - Bioaccumulation of As, Cd, Cu, Pb and Zn by Macrobrachium prawns was observed to
      occur in the Strickland River downstream of a gold mine at Porgera, Papua New
      Guinea. This was despite the total metal concentrations of waters and sediments
      indicating no difference from reference sites within tributaries. To provide
      information on potential sources and bioavailability of metals to prawns, an
      extensive range of analyses were made on waters, suspended solids, deposited
      sediments and plant materials within the river system. Dissolved metal
      concentrations were mostly sub-micrograms per liter and no major differences
      existed in concentrations or speciation between sites within the Strickland River
      or its tributaries. Similarly, no differences were detected between sites for
      total or dilute acid-extractable metal concentrations in bed sediments and plant
      materials, which may be ingested by the prawns. However, the rivers in this
      region are highly turbid and the dilute acid-extractable cadmium and zinc
      concentrations in suspended solids were greater at sites in the Strickland River
      than at sites in tributaries. The results indicated that mine-derived inputs
      increased the proportion of these forms of metals or metalloids in the Strickland
      River. These less strongly bound metals and metalloids would be more bioavailable
      to the prawns via the dietary pathway. The results highlighted many of the
      difficulties in using routine monitoring data without information on metal
      speciation to describe metal uptake and predict potential effects when
      concentrations are low and similar to background. The study indicated that the
      monitoring of contaminant concentrations in organisms that integrate the exposure
      from multiple exposure routes and durations may often be more effective for
      detecting impacts than intermittent monitoring of contaminants in waters and
      sediments. 

PMID- 24014224
TI  - Decision support tool for soil sampling of heterogeneous pesticide (chlordecone)
      pollution.
AB  - When field pollution is heterogeneous due to localized pesticide application, as
      is the case of chlordecone (CLD), the mean level of pollution is difficult to
      assess. Our objective was to design a decision support tool to optimize soil
      sampling. We analyzed the CLD heterogeneity of soil content at 0-30- and 30-60-cm
      depth. This was done within and between nine plots (0.4 to 1.8 ha) on andosol and
      ferralsol. We determined that 20 pooled subsamples per plot were a satisfactory
      compromise with respect to both cost and accuracy. Globally, CLD content was
      greater for andosols and the upper soil horizon (0-30 cm). Soil organic carbon
      cannot account for CLD intra-field variability. Cropping systems and tillage
      practices influence the CLD content and distribution; that is CLD pollution was
      higher under intensive banana cropping systems and, while upper soil horizon was
      more polluted than the lower one with shallow tillage (<40 cm), deeper tillage
      led to a homogenization and a dilution of the pollution in the soil profile. The
      decision tool we proposed compiles and organizes these results to better assess
      CLD soil pollution in terms of sampling depth, distance, and unit at field scale.
      It accounts for sampling objectives, farming practices (cropping system,
      tillage), type of soil, and topographical characteristics (slope) to design a
      relevant sampling plan. This decision support tool is also adaptable to other
      types of heterogeneous agricultural pollution at field level.

PMID- 24014225
TI  - A Cr(VI)-reducing Microbacterium sp. strain SUCR140 enhances growth and yield of
      Zea mays in Cr(VI) amended soil through reduced chromium toxicity and improves
      colonization of arbuscular mycorrhizal fungi.
AB  - Pot culture experiments were conducted in a glasshouse to evaluate the effects of
      four efficient Cr(VI)-reducing bacterial strains (SUCR44, SUCR140, SUCR186, and
      SUCR188) isolated from rhizospheric soil, and four arbuscular mycorrhizal fungi
      (AMF-Glomus mosseae, G. aggregatum, G. fasciculatum, and G. intraradices) alone
      or in combination, on Zea mays in artificially Cr(VI)-amended soil. Presence of a
      strain of Microbacterium sp. SUCR140 reduced the chromate toxicity resulting in
      improved growth and yields of plants compared to control. The bioavailability of
      Cr(VI) in soil and its uptake by the plant reduced significantly in SUCR140
      treated plants; the effects of AMF, however, either alone or in presence of
      SUCR140 were not significant. On the other hand, presence of AMF significantly
      restricted the transport of chromium from root to the aerial parts of plants. The
      populations of AMF chlamydospores in soil and its root colonization improved in
      presence of SUCR140. This study demonstrates the usefulness of an efficient
      Cr(VI)-reducing bacterial strain SUCR140 in improving yields probably through
      reducing toxicity to plants by lowering bioavailability and uptake of Cr(VI) and
      improving nutrient availability through increased mycorrhizal colonization which
      also restricted the transport of chromium to the aerial parts. 

PMID- 24014226
TI  - Association between air quality and quality of life.
AB  - Air quality-or its converse, air pollution-is a significant risk factor for human
      health. Recent studies have reported association between air pollution and human
      health. There are numerous diseases that may be caused by air pollution such as
      respiratory infection, lung cancer, cardiovascular disease, chronic obstructive
      pulmonary disease, and asthma. In this study, the relationship between air
      quality and quality of life was examined by using canonical correlation analysis.
      Data of this study was collected from 27 countries. WHO statistics were used as
      the main source of quality of life data set (Y variables set). European
      Environment Agency statistics and (for outdoor air-PM10) WHO statistics were used
      as the main source of air quality data set (X variables set). It is found that
      there are significant positive correlation between air quality and quality of
      life. 

PMID- 24014227
TI  - Comparison of species sensitivity distributions for species from China and the
      USA.
AB  - China has recently commenced water quality criteria (WQC) research using the
      species sensitivity distribution (SSD) method; however, it is difficult to obtain
      sufficient native species toxicity data for thousands of contaminants. In this
      study, the feasibility of using non-native toxicity data in deriving native WQC
      was analyzed. We constructed SSDs based on acute toxicity data of species from
      China and the USA for eight priority pollutants, and compared the sensitivities
      of different taxonomic groups between the two countries. The results showed that
      the SSD method of log-logistic distribution fit the toxicity data of different
      taxa well. The comparison of sensitivity distribution and hazardous concentration
      for 5% of the species and 50% of the species showed that there was no significant
      difference between Chinese and American taxa. It could be feasible to use
      toxicity data from the USA to provide a temporary way to protect organisms in
      China in emergency situations or for management of priority pollutants when
      native toxicity data are lacking.

PMID- 24014228
TI  - The appropriation process of the belief in a just world.
AB  - Research on the belief in a just world (BJW) has been developing since the mid
      60s. However, studies have been mainly developed from an individual differences
      perspective. As a consequence there are no studies that analyze the cognitive
      processes implied in the appropriation of the BJW during the socialization
      processes that occur in infancy and onwards. The main purpose of this paper is
      therefore to analyze this psychological process from childhood to adolescence.
      The study was carried out with a convenience sample of children and adolescents
      (N = 216) from Buenos Aires, between 6 and 17 years old, who participated in an
      interview guided by the piagetian clinical method. Results indicate that during
      the appropriation process of the BJW participants reconstruct this belief to make
      it coherent with hypothetical deductive thinking. This is expressed in three
      different justifications that the individuals give to justify their BJW: immanent
      justice, social reciprocity and personal merit. Yet, the appropriation process is
      incomplete. In the majority of the adolescents a magical thinking remains,
      constituting a state of cognitive polyphasia expressed in oscillating answers. In
      conclusion, the BJW is not a previous social condition transmitted from one
      generation to another. Its appropriation goes beyond the mere reproduction of
      social beliefs and involves a conceptual reconstruction.

PMID- 24014229
TI  - Dissociative disorders in medical settings.
AB  - Despite the challenges of conducting research on dissociation and the
      dissociative disorders, our understanding has grown greatly over the past three
      decades, including our knowledge of the often overlooked sensorimotor
      manifestations of dissociation, more commonly referred to as somatoform
      dissociation. This article will first review the definitions and presentations of
      dissociation in general along with recent research on the concept of somatoform
      dissociation. Then, each of the dissociative disorders and conversion disorder
      will be discussed in further detail as well as how they might present in a
      medical setting. Current recommendations for diagnosis and treatment will also be
      provided. 

PMID- 24014230
TI  - Supraglottic airway devices versus tracheal intubation for airway management
      during general anaesthesia in obese patients.
AB  - BACKGROUND: The number of obese patients requiring general anaesthesia is likely
      to increase in coming years, and obese patients pose considerable challenges to
      the anaesthetic team. Tracheal intubation may be more difficult and risk of
      aspiration of gastric contents into the lungs is increased in obese patients.
      Supraglottic airway devices (SADs) offer an alternative airway to traditional
      tracheal intubation with potential benefits, including ease of fit and less
      airway disturbance. Although SADs are now widely used, clinical concerns remain
      that their use for airway management in obese patients may increase the risk of
      serious complications. OBJECTIVES: We wished to examine whether supraglottic
      airway devices can be used as a safe and effective alternative to tracheal
      intubation in securing the airway during general anaesthesia in obese patients
      (with a body mass index (BMI) > 30 kg/m(2)). SEARCH METHODS: We searched for
      eligible trials in the following databases: Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library, Issue 8, 2012), MEDLINE via
      Ovid (from 1985 to 9 September 2012) and EMBASE via Ovid (from 1985 to 9
      September 2012). The Cochrane highly sensitive filter for randomized controlled
      trials was applied in MEDLINE and EMBASE. We also searched trial registers such
      as www.clinicaltrials.gov and the Current Controlled Clinical Trials Website
      (http://www.controlled-trials.com/) for ongoing trials. The start date of these
      searches was limited to 1985, shortly before the first SAD was introduced, in
      1988. We undertook forward and backward citation tracing for key review articles
      and eligible articles identified through the electronic resources. SELECTION
      CRITERIA: We considered all randomized controlled trials of participants aged 16
      years and older with a BMI > 30 kg/m(2) undergoing general anaesthesia. We
      compared the use of any model of SAD with the use of tracheal tubes (TTs) of any
      design. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures
      expected by The Cochrane Collaboration. Two review authors independently assessed
      trial quality and extracted data, including information on adverse events. We
      contacted study authors for additional information. If sufficient data were
      available, results were presented as pooled risk ratios (RRs) with 95% confidence
      intervals (CIs) based on random-effects models (inverse variance method). We
      employed the Chi(2) test and calculated the I(2) statistic to investigate study
      heterogeneity. MAIN RESULTS: We identified two eligible studies, both comparing
      the use of one model of SAD, the ProSeal laryngeal mask airway (PLMA) with a TT,
      with a total study population of 232. One study population underwent laparoscopic
      surgery. The included studies were generally of high quality, but there was an
      unavoidable high risk of bias in the main airway variables, such as change of
      device or laryngospasm, as the intubator could not be blinded. Many outcomes
      included data from one study only.A total of 5/118 (4.2%) participants randomly
      assigned to PLMA across both studies were changed to TT insertion because of
      failed or unsatisfactory placement of the device. Postoperative episodes of
      hypoxaemia (oxygen saturation < 92% whilst breathing air) were less common in the
      PLMA groups (RR 0.27, 95% CI 0.10 to 0.72). We found a significant postoperative
      difference in mean oxygen saturation, with saturation 2.54% higher in the PLMA
      group (95% CI 1.09% to 4.00%). This analysis showed high levels of heterogeneity
      between results (I(2) = 71%). The leak fraction was significantly higher in the
      PLMA group, with the largest difference seen during abdominal insufflation-a 6.4%
      increase in the PLMA group (95% CI 3.07% to 9.73%).No cases of pulmonary
      aspiration of gastric contents, mortality or serious respiratory complications
      were reported in either study. We are therefore unable to present effect
      estimates for these outcomes.In all, 2/118 participants with a PLMA suffered
      laryngospam or bronchospasm compared with 4/114 participants with a TT. The
      pooled estimate shows a non-significant reduction in laryngospasm in the PLMA
      group (RR 0.48, 95% CI 0.09 to 2.59).Postoperative coughing was less common in
      the PLMA group (RR 0.10, 95% CI 0.03 to 0.31), and there was no significant
      difference in the risk of sore throat or dysphonia (RR 0.25, 95% CI 0.03 to
      2.13). On average, PLMA placement took 5.9 seconds longer than TT placement (95%
      CI 3 seconds to 8.8 seconds). There was no significant difference in the
      proportion of successful first placements of a device, with 33/35 (94.2%) first
      time successes in the PLMA group and 32/35 (91.4%) in the TT group. AUTHORS'
      CONCLUSIONS: We have inadequate information to draw conclusions about safety, and
      we can only comment on one design of SAD (the PLMA) in obese patients. We
      conclude that during routine and laparoscopic surgery, PLMAs may take a few
      seconds longer to insert, but this is unlikely to be a matter of clinical
      importance. A failure rate of 3% to 5% can be anticipated in obese patients.
      However, once fitted, PLMAs provide at least as good oxygenation, with the caveat
      that the leak fraction may increase, although in the included studies, this did
      not affect ventilation. We found significant improvement in oxygenation during
      and after surgery, indicating better pulmonary performance of the PLMA, and
      reduced postoperative coughing, suggesting better recovery for patients.

PMID- 24014231
TI  - Cdc42 regulates Schwann cell radial sorting and myelin sheath folding through
      NF2/merlin-dependent and independent signaling.
AB  - The Rho family GTPase Cdc42 has been implicated in developmental Schwann cell
      (SC) proliferation, providing sufficient SCs for radial sorting of axons
      preceding SC differentiation in the peripheral nervous system. We generated Cdc42
      conditional knockout (Cdc42-CKO) mice and confirmed aberrant axon sorting in
      Cdc42-CKO nerves. In adult Cdc42-CKO nerves, blood vessels were enlarged, and
      mature Remak bundles containing small axons were absent. Abnormal infoldings and
      outfoldings of myelin sheaths developed in Cdc42-CKO nerves, mimicking
      pathological features of Charcot-Marie-Tooth (CMT) disease. The NF2/merlin tumor
      suppressor has been implicated up- and down-stream of Cdc42. In Cdc42-CKO;NF2-del
      double mutant mice, radial sorting defects seen in Cdc42-CKO nerves were rescued,
      while changes in myelin sheaths in Cdc42-CKO nerves were not. Phosphorylation of
      Focal adhesion kinase (FAK) and P-GSK3beta, as well as expression of beta-catenin
      were decreased in Cdc42-CKO nerves, and these changes were rescued by NF2/merlin
      mutation in Cdc42-CKO;NF2-del double mutant mice. Thus, Cdc42 regulates SC radial
      sorting in vivo through NF2/merlin dependent signaling pathways, while Cdc42
      modulation of myelin sheath folding is NF2/merlin independent.

PMID- 24014232
TI  - From the galleries to the clinic: applying art museum lessons to patient care.
AB  - Increasingly, medical educators integrate art-viewing into curricular
      interventions that teach clinical observation-often with local art museum
      educators. How can cross-disciplinary collaborators explicitly connect the skills
      learned in the art museum with those used at the bedside? One approach is for
      educators to align their pedagogical approach using similar teaching methods in
      the separate contexts of the galleries and the clinic. We describe two linked
      pedagogical exercises--Visual Thinking Strategies (VTS) in the museum galleries
      and observation at the bedside--from "Training the Eye: Improving the Art of
      Physical Diagnosis," an elective museum-based course at Harvard Medical School.
      It is our opinion that while strategic interactions with the visual arts can
      improve skills, it is essential for students to apply them in a clinical context
      with faculty support-requiring educators across disciplines to learn from one
      another.

PMID- 24014233
TI  - Insights into stabilization of a viral protein cage in templating complex
      nanoarchitectures: roles of disulfide bonds.
AB  - As a typical protein nanostructure, virus-based nanoparticle (VNP) of simian
      virus 40 (SV40), which is composed of pentamers of the major capsid protein of
      SV40 (VP1), has been successfully employed in guiding the assembly of different
      nanoparticles (NPs) into predesigned nanostructures with considerable stability.
      However, the stabilization mechanism of SV40 VNP remains unclear. Here, the
      importance of inter-pentamer disulfide bonds between cysteines in the
      stabilization of quantum dot (QD)-containing VNPs (VNP-QDs) is comprehensively
      investigated by constructing a series of VP1 mutants of cysteine to serine.
      Although the presence of a QD core can greatly enhance the assembly and stability
      of SV40 VNPs, disulfide bonds are vital to stability of VNP-QDs. Cysteine at
      position 9 (C9) and C104 contribute most of the disulfide bonds and play
      essential roles in determining the stability of SV40 VNPs as templates to guide
      assembly of complex nanoarchitectures. These results provide insightful clues to
      understanding the robustness of SV40 VNPs in organizing suprastructures of
      inorganic NPs. It is expected that these findings will help guide the future
      design and construction of protein-based functional nanostructures. 

PMID- 24014234
TI  - Impact of Epstein-Barr virus load, virus genotype, and frequency of the 30 bp
      deletion in the viral BNLF-1 gene in patients harboring the human
      immunodeficiency virus.
AB  - Patients infected with the human immunodeficiency virus (HIV) are at higher risk
      of developing Epstein-Barr Virus (EBV)-associated lymphomas. The usefulness of
      monitoring EBV in peripheral blood mononuclear cells (PBMCs) of patients infected
      with HIV has not been established. The aim of this study was to evaluate the EBV
      viral load in PBMCs, the frequency of viral genotypes, and the presence of the 30
      bp deletion in the BNLF-1 gene. DNA samples from 156 patients attending the
      HIV/AIDS Day Clinic at Botucatu School of Medicine, Sao Paulo State University
      were evaluated. The EBV viral load was detectable by real time PCR in 123/156
      (78.8%) cases and was higher in patients not receiving antiretroviral treatment
      or under therapeutic failure than in patients under successful highly active
      antiretroviral therapy (HAART) (P = 0.0076). Overall, the profile of patients
      with high EBV viral load included elevated HIV viremia (P = 0.0005), longer time
      of HIV diagnosis (P = 0.0026), and increased levels of T CD8 (+) lymphocytes (P =
      0.0159). The successful amplification of the EBNA-2 gene by nested-PCR was
      achieved in 95 of 123 (77.2%) cases, of which 75.8% were EBV-1, 9.5% EBV-2, and
      14.7% were co-infected with both EBV-1 and -2. The analysis of the BNLF-1 gene
      was possible in 99 of 123 (80.5%) cases, of which 50.5% had the 30-bp deletion.
      EBV-1 was more common than EBV-2, which may reflect the fact that the cohort was
      predominantly Caucasian and heterosexual.

PMID- 24014235
TI  - Infection-induced anaemia: a cross-sectional study of 14,636 German travellers
      aged 20-49 years.
AB  - BACKGROUND: Anaemia is a frequently diagnosed condition which can develop as a
      consequence of numerous factors, including infectious diseases (IDs). Travelling,
      especially in sub-/tropical regions, leads to an elevated risk of contracting
      IDs. The aim of our study was to assess the epidemiological significance of IDs
      in inducing anaemia among a large cohort of returned travellers. METHODS: This
      was a cross-sectional study in which data on 17,009 returned travellers aged 20
      49 years who consulted the travel medicine clinic of the University of Munich
      between 1999 and 2011 were retrieved and analysed. RESULTS: Of the returned
      travellers, 8.3 % (6.0 % of males/10.4 % of females) were diagnosed with anaemia.
      The prevalence of anaemia was significantly elevated among patients of African
      (21.4/28.3 %) and Asian (11.6/15.7 %) origin. When the study population was
      restricted to the 14,636 travellers of German origin, 7.1 % of the returned
      travellers (4.6/9.6 %) were diagnosed with anaemia. The prevalence was
      significantly elevated among patients who travelled for >30 days (5.7 of
      males/10.6 % of females) and for male travellers visiting friends and relatives
      (7.7 %). However, these correlations were confounded by malaria. The prevalence
      of anaemia was significantly elevated only among returned travellers diagnosed
      with malaria (36.1 of males/26.9 % of females) and with symptomatic intestinal
      Entamoeba histolytica infections (30.0/33.3 %). CONCLUSION: Following the
      exclusion of confounding by malaria from the statistical analysis, the prevalence
      of anaemia was found to be significantly elevated among patients of African and
      Asian origin, and among patients of German origin who had travelled for >30 days,
      it could be mainly attributable to chronic, long-lasting causes. Although more
      than 550 travel-associated IDs were assessed in our study, only symptomatic
      intestinal Entamoeba histolytica infections and, to an even larger extent,
      malaria were determined to be of epidemiological significance for inducing
      anaemia among travellers.

PMID- 24014236
TI  - Lipid-bilayer-spanning DNA nanopores with a bifunctional porphyrin anchor.

PMID- 24014237
TI  - Interpretation in cross-language research: tongues-tied in the health care
      interview?
AB  - Medication prescribing and use is a normative aspect of health care for the
      elderly, rendering medication taking by elderly persons problematic. In an
      earlier qualitative study, we examined how medicine-use is negotiated
      (used/refused/resisted, and assessed against expected outcomes) by older persons
      with limited fluency in English-the main language of health care in the study
      setting. In the present article, we describe a reflexive methodological review of
      that study's design, with a particular focus placed on interpreter-mediated data
      collection. We illustrate that what was heard in open-ended interviews (what
      became data) was influenced by not only what was asked and how, but also by how
      the interpreter 'heard' and conveyed dialogue to and from study participants. We
      illustrate differing accounts of the dialogue between an interviewer and
      participant provided via real-time interpretation and through a reflexive re
      interpretation of talk-to-text transcripts, reflecting the different stakes in
      the research, and different capital available to study- and review-interpreters.
      Implications for research design and practice of cross-cultural and cross
      language research are highlighted. 

PMID- 24014239
TI  - The interaction between factor H and VWF increases factor H cofactor activity and
      regulates VWF prothrombotic status.
AB  - Vascular endothelial cells (ECs) link hemostasis, thrombosis, and complement. ECs
      synthesize both the clotting initiator von Willebrand factor (VWF) and the
      complement regulator factor H (FH). VWF is stored in EC Weibel-Palade bodies
      (WPBs), but the intracellular location of FH is not well defined. We found that
      FH colocalizes with VWF in WPBs of human umbilical vein ECs. Moreover, FH bound
      to VWF with an apparent nanomolar affinity and the complex was present in normal
      plasma. The binding of VWF to FH enhanced FH cofactor activity toward factor I
      mediated downregulation of complement activation. Besides, this interaction
      inhibited ADAMTS13-mediated proteolysis of VWF and promoted platelet aggregation.
      Here, we describe a novel interaction between complement and hemostasis. The
      simultaneous secretion of VWF and FH by activated ECs may promote adhesion of
      platelets to endothelial injury sites to assure wound healing, simultaneously
      dampening the proinflammatory effect of complement to limit bystander tissue
      damage. 

PMID- 24014238
TI  - IL-21 and CD40L signals from autologous T cells can induce antigen-independent
      proliferation of CLL cells.
AB  - Chronic lymphocytic leukemia (CLL) cells multiply in secondary lymphoid tissue,
      but the mechanisms leading to their proliferation are still uncertain. In
      addition to B-cell receptor (BCR)-triggered signals, other microenvironmental
      factors might well be involved. In proliferation centers, leukemic B cells are in
      close contact with CD4(+)CD40L(+) T cells. Therefore, we here dissected the
      signals provided by autologous activated T cells (Tact) to CLL cells. Although
      the gene expression profile induced by Tact was highly similar to that induced by
      sole CD40 signaling, an obvious difference was that Tact induced proliferation of
      CLL cells. We determined that stimulation with only CD40L+IL-21 was sufficient to
      induce robust proliferation in CLL cells. We then defined an interleukin (IL)-21
      induced gene signature in CLL, containing components of Janus kinase/signal
      transducer and activator of transcription and apoptosis pathways, and this
      signature could be detected in lymph node (LN) samples from patients. Finally, we
      could detect IL-21 RNA and protein in LN, and IL-21 production ex vivo by LN
      CD4(+)CXCR5(+) follicular helper T cells. These results indicate that in addition
      to BCR signaling, activated T cells might contribute to CLL cell proliferation
      via CD40 and IL-21. Targeting these signaling pathways might offer new venues for
      treatment of CLL. 

PMID- 24014240
TI  - Protein S levels and the risk of venous thrombosis: results from the MEGA case
      control study.
AB  - In thrombophilic families, protein S deficiency is clearly associated with venous
      thrombosis. We aimed to determine whether the same holds true in a population
      based case-control study (n = 5317). Subjects were regarded protein S deficient
      when protein S levels were < 2.5th percentile of the controls. Free and total
      protein S deficiency was not associated with venous thrombosis: free protein S <
      53 U/dL, odds ratio [OR] 0.82 (95% confidence interval [CI], 0.56-1.21) and total
      protein S < 68 U/dL, OR 0.90 (95% CI, 0.62-1.31). When lower cutoff values were
      applied, it appeared that subjects at risk of venous thrombosis could be
      identified at levels < 0.10th percentile of free protein S (< 33 U/dL, OR 5.4;
      95% CI, 0.61-48.8). In contrast, even extremely low total protein S levels were
      not associated with venous thrombosis. PROS1 was sequenced in 48 subjects with
      free protein S level < 1st percentile (< 4 6 U/dL), and copy number variations
      were investigated in 2718 subjects, including all subjects with protein S (free
      or total) < 2.5th percentile. Mutations in PROS1 were detected in 5 patients and
      5 controls reinforcing the observation that inherited protein S deficiency is
      rare in the general population. Protein S testing and PROS1 testing should not be
      considered in unselected patients with venous thrombosis.

PMID- 24014241
TI  - Inhibiting glutamine uptake represents an attractive new strategy for treating
      acute myeloid leukemia.
AB  - Cancer cells require nutrients and energy to adapt to increased biosynthetic
      activity, and protein synthesis inhibition downstream of mammalian target of
      rapamycin complex 1 (mTORC1) has shown promise as a possible therapy for acute
      myeloid leukemia (AML). Glutamine contributes to leucine import into cells, which
      controls the amino acid/Rag/mTORC1 signaling pathway. We show in our current
      study that glutamine removal inhibits mTORC1 and induces apoptosis in AML cells.
      The knockdown of the SLC1A5 high-affinity transporter for glutamine induces
      apoptosis and inhibits tumor formation in a mouse AML xenotransplantation model.
      l-asparaginase (l-ase) is an anticancer agent also harboring glutaminase
      activity. We show that l-ases from both Escherichia coli and Erwinia chrysanthemi
      profoundly inhibit mTORC1 and protein synthesis and that this inhibition
      correlates with their glutaminase activity levels and produces a strong apoptotic
      response in primary AML cells. We further show that l-ases upregulate glutamine
      synthase (GS) expression in leukemic cells and that a GS knockdown enhances l-ase
      induced apoptosis in some AML cells. Finally, we observe a strong autophagic
      process upon l-ase treatment. These results suggest that l-ase anticancer
      activity and glutamine uptake inhibition are promising new therapeutic strategies
      for AML. 

PMID- 24014242
TI  - Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a
      pooled analysis of 1546 patients.
AB  - Limited comparative data exist for the treatment of HIV-associated non-Hodgkin
      lymphoma. We analyzed pooled individual patient data for 1546 patients from 19
      prospective clinical trials to assess treatment-specific factors (type of
      chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use)
      and their influence on the outcomes complete response (CR), progression free
      survival (PFS), and overall survival (OS). In our analysis, rituximab was
      associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS
      (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with
      cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial
      therapy with more dose-intense regimens resulted in better CR rates (ACVBP
      [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70;
      P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001)
      and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide,
      prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide
      (EPOCH) was associated with significantly better OS in diffuse large B-cell
      lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved
      CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07).
      These findings provide supporting evidence for current patterns of care where
      definitive evidence is unavailable. 

PMID- 24014243
TI  - The control of hematopoietic stem cell maintenance, self-renewal, and
      differentiation by Mysm1-mediated epigenetic regulation.
AB  - Epigenetic histone modifications play critical roles in the control of self
      renewal and differentiation of hematopoietic stem cells (HSCs). Mysm1 is a
      recently identified histone H2A deubiquitinase with essential and intrinsic roles
      for maintaining functional HSCs. In this study, in addition to confirming this
      function of Mysm1, by using Mysm1-deficient (Mysm1(-/-)) mice, we provide more
      evidence for how Mysm1 controls HSC homeostasis. Mysm1 deletion drives HSCs from
      quiescence into rapid cycling and increases their apoptotic rate, resulting in an
      exhaustion of the stem cell pool, which leads to an impaired self-renewal and
      lineage reconstituting abilities in the Mysm1-deficient mice. Our study
      identified Gfi1 as one of the candidate genes responsible for the HSC defect in
      Mysm1-deficient mice. Mechanistic studies revealed that Mysm1 modulates histone
      modifications and directs the recruitment of key transcriptional factors such as
      Gata2 and Runx1 to the Gfi1 locus in HSCs. We found that Mysm1 directly
      associates with the Gfi1 enhancer element and promotes its transcription through
      Gata2 and Runx1 transactivation. Thus, our study not only elaborates on the
      initial reports of Mysm1 association with HSC homeostasis but also delineates a
      possible epigenetic mechanism through which Mysm1 carries out this function in
      the HSCs. 

PMID- 24014244
TI  - MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic
      cells.
AB  - During microbial infections, plasmacytoid dendritic cells (pDCs) are a main
      source of type I interferons alpha/beta (IFN-alpha/-beta). Nucleic acids from
      microbes are sensed by Toll-like receptors 7/9 (TLR7/9), which are selectively
      expressed in pDCs. Activated pDCs also produce proinflammatory cytokines and
      upregulate costimulatory molecules. Together, this equips pDCs with the ability
      to prime T, B, and NK cells and conventional DCs, thereby initiating adaptive
      immune responses. To avoid deleterious effects to the host, tight regulation of
      pDC activation is required. Despite data linking aberrant activation of pDCs with
      autoimmune diseases, little is known about mechanisms controlling pDC activation.
      Here, we investigated the role of microRNA-146a (miR-146a) in TLR pathway
      regulation in human pDCs. MiR-146a expression was induced upon TLR7/9 signaling.
      Furthermore, ectopic miR-146a expression effectively impaired TLR-mediated
      signaling in pDCs as TLR-induced nuclear factor-kappaB activation was reduced.
      This consequently diminished the production of proinflammatory cytokines and
      reduced pDC survival. Moreover, miR-146a-expressing pDCs had decreased ability to
      induce CD4(+) T-cell proliferation likely due to reduced expression levels of
      major histocompatibility complex class II and costimulatory molecules. Our data
      unravel the crucial immunomodulatory role of miR-146a in pDCs and may add to our
      understanding of aberrant responses in autoimmune diseases. 

PMID- 24014246
TI  - Toxicokinetics and coagulopathy threshold of the rodenticide diphacinone in
      eastern screech-owls (Megascops asio).
AB  - In the United States, new regulations on second-generation anticoagulant
      rodenticides will likely be offset by expanded use of first-generation
      anticoagulant rodenticides. In the present study, eastern screech-owls (Megascops
      asio) were fed 10 ug diphacinone/g wet weight food for 7 d, and recovery was
      monitored over a 21-d postexposure period. By day 3 of exposure, diphacinone
      (DPN) was detected in liver (1.63 ug/g wet wt) and kidney (5.83 ug/g) and
      coagulopathy was apparent. By day 7, prothrombin time (PT) and Russell's viper
      venom time (RVVT) were prolonged, and some individuals were anemic. Upon
      termination of exposure, coagulopathy and anemia were resolved within 4 d, and
      residues decreased to <0.3 ug/g by day 7. Liver and kidney DPN elimination
      occurred in 2 phases (initial rapid loss, followed by slower loss rate), with
      overall half-lives of 11.7 d and 2.1 d, respectively. Prolonged PT and RVVT
      occurred in 10% of the exposed owls with liver DPN concentrations of 0.122 ug/g
      and 0.282 ug/g and in 90% of the owls with liver concentrations of 0.638 ug/g and
      0.361 ug/g. These liver residue levels associated with coagulopathy fall in the
      range of values reported in raptor mortality incidents involving DPN. These
      tissue-based toxicity reference values for coagulopathy in adult screech-owls
      have application for interpreting nontarget mortality and assessing the hazard of
      DPN in rodent-control operations. Diphacinone exposure evokes toxicity in raptors
      within a matter of days; but once exposure is terminated, recovery of hemostasis
      occurs rapidly.

PMID- 24014245
TI  - Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low
      dose dexamethasone in relapsed or progressive multiple myeloma.
AB  - We previously reported a phase 1b dose-escalation study of carfilzomib,
      lenalidomide, and low-dose dexamethasone (CRd) in relapsed or progressive
      multiple myeloma where the maximum planned dose (MPD) was carfilzomib 20 mg/m2
      days 1 and 2 of cycle 1 and 27 mg/m2 days 8, 9, 15, 16, and thereafter;
      lenalidomide 25 mg days 1 to 21; and dexamethasone 40 mg once weekly on 28-day
      cycles. Herein, we present results from the phase 2 dose expansion at the MPD,
      focusing on the 52 patients enrolled in the MPD cohort. Median follow-up was 24.4
      months. In the MPD cohort, overall response rate (ORR) was 76.9% with median time
      to response of 0.95 month (range, 0.5-4.6) and duration of response (DOR) of 22.1
      months. Median progression-free survival was 15.4 months. ORR was 69.2% in
      bortezomib-refractory patients and 69.6% in lenalidomide-refractory patients with
      median DOR of 22.1 and 10.8 months, respectively. A median of 9.5 (range, 1-45)
      carfilzomib cycles were started with 7.7% of patients requiring carfilzomib dose
      reductions and 19.2% discontinuing CRd due to adverse events (AEs). Grade 3/4 AEs
      included lymphopenia (48.1%), neutropenia (32.7%), thrombocytopenia (19.2%), and
      anemia (19.2%). CRd at the MPD was well tolerated with robust, rapid, and durable
      responses.

PMID- 24014247
TI  - Biphasic calcium phosphate loading on polycaprolactone/poly(lacto-co-glycolic
      acid) membranes for improved tensile strength, in vitro biocompatibility, and in
      vivo tissue regeneration.
AB  - Electrospun polycaprolactone and poly(lacto-co-glycolide) membranes were loaded
      with biphasic calcium phosphate powder to facilitate osteoconductivity. Different
      concentrations of biphasic calcium phosphate powder were added to the polymer
      solution, and successful loading was confirmed by X-ray diffraction analysis,
      transmission electron microscope, and scanning electron microscope with energy
      dispersive spectroscopy visualization. The effect of the added biphasic calcium
      phosphate on the polymer membrane was investigated in terms of the material's
      tensile strength and strain, in vitro cytocompatibility, and in vivo tissue
      regeneration. It was observed that the tensile strength of the membranes
      increased with the addition of the biphasic calcium phosphate powder. Immersion
      in simulated body fluid solution for seven days leads to the formation of apatite
      like deposits in the fibers, which further improved the mechanical stability.
      Moreover, proliferation and adhesion of osteoblast-like cells were more apparent
      upon the addition of the biphasic calcium phosphate powder as seen with the
      increasing cell density from (3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay and micrographs from scanning electron
      microscope and confocal microscopy. Sample membranes were also implanted to
      investigate the membrane's ability to regenerate bone in a rat calvarium.
      Histological staining and micro-CT histomorphometric analyses showed neo-bone
      formation in the implanted rat skull.

PMID- 24014248
TI  - Bioaccumulation and excretion of enantiomers of myclobutanil in Tenebrio molitor
      larvae through dietary exposure.
AB  - The bioaccumulation and excretion of enantiomers of myclobutanil in Tenebrio
      molitor larvae through dietary exposure under laboratory conditions were
      investigated using high-performance liquid chromatography tandem mass
      spectrometry (HPLC-MS/MS) based on a ChiralcelOD-3R [cellulosetris-tris-(3, 5
      dichlorophenyl-carbamate)] column. The wheat bran fed to Tenebrio molitor larvae
      was spiked with racemic myclobutanil at two dose levels of 20 mg/kg and 2 mg/kg
      (dry weight). The results showed that there was a significant trend of
      enantioselective bioaccumulation in the larvae with a preferential accumulation
      of (-)-myclobutanil in 20 mg/kg dose exposure, but it was not obviously observed
      in the 2 mg/kg dose group. A kinetic model considering enantiomerization between
      the two enantiomers based on first-order reactions was built and the rate
      constants were estimated to discuss the kinetic reason for the different
      concentrations of individual enantiomers in the larvae. The approximations
      implied an inversion between the two enantiomers with a relatively higher rate of
      the inversion from (-)-myclobutanil to (+)-myclobutanil. Meanwhile, analysis of
      data of excretion samples suggested the active excretion is probably an important
      pathway for the insect to eliminate myclobutanil rapidly with
      nonenantioselectivity as a passive transport process, which was consistent with
      the low accumulation efficiency of myclobutanil measured by BAF (bioaccumulation
      factor).

PMID- 24014249
TI  - Predictors of long-term HIV RNA suppression on darunavir/ritonavir monotherapy in
      the MONET trial.

PMID- 24014252
TI  - A Three-dimensional Polymer Scaffolding Material Exhibiting a Zero Poisson's
      Ratio.
AB  - Poisson's ratio describes the degree to which a material contracts (expands)
      transversally when axially strained. A material with a zero Poisson's ratio does
      not transversally deform in response to an axial strain (stretching). In tissue
      engineering applications, scaffolding having a zero Poisson's ratio (ZPR) may be
      more suitable for emulating the behavior of native tissues and accommodating and
      transmitting forces to the host tissue site during wound healing (or tissue
      regrowth). For example, scaffolding with a zero Poisson's ratio may be beneficial
      in the engineering of cartilage, ligament, corneal, and brain tissues, which are
      known to possess Poisson's ratios of nearly zero. Here, we report a 3D
      biomaterial constructed from polyethylene glycol (PEG) exhibiting in-plane
      Poisson's ratios of zero for large values of axial strain. We use digital micro
      mirror device projection printing (DMD-PP) to create single- and double-layer
      scaffolds composed of semi re-entrant pores whose arrangement and deformation
      mechanisms contribute the zero Poisson's ratio. Strain experiments prove the zero
      Poisson's behavior of the scaffolds and that the addition of layers does not
      change the Poisson's ratio. Human mesenchymal stem cells (hMSCs) cultured on
      biomaterials with zero Poisson's ratio demonstrate the feasibility of utilizing
      these novel materials for biological applications which require little to no
      transverse deformations resulting from axial strains. Techniques used in this
      work allow Poisson's ratio to be both scale-independent and independent of the
      choice of strut material for strains in the elastic regime, and therefore ZPR
      behavior can be imparted to a variety of photocurable biomaterial.

PMID- 24014251
TI  - Adjustment for smoking does not alter the FOXO3A association with longevity.
AB  - Human longevity is a multifactorial phenotype influenced by both genetic and
      environmental factors. Despite its heritability of 25-32 %, the genetic
      background of longevity is as yet largely unexplained. Apart from APOE status,
      variation in the FOXO3A gene is the only confirmed genetic contributor to
      survival into old age. On the other hand, FOXO3A activity is known to be
      downregulated in various cancers, and the gene was recently identified as a novel
      deletion hotspot in human lung adenocarcinoma. In view of the strong association
      between smoking and lung cancer, we set out to explore whether smoking modifies
      the known association between FOXO3A variation and longevity. To this end, we
      conducted a case-control study in two different populations, drawing upon
      extensive collections of old-aged individuals and younger controls available to
      us (1,613 German centenarians/nonagenarians and 1,104 controls; 1,088 Danish
      nonagenarians and 736 controls). In the German sample, 21 single nucleotide
      polymorphisms (SNPs) from the FOXO3A gene region were genotyped, whereas 15
      FOXO3A SNPs were analyzed in the Danish sample. Eight SNPs were typed in both
      populations. Logistic regression analysis revealed that adjustment for smoking
      does not systematically alter the association between FOXO3A variation and
      longevity in neither population. Our analysis therefore suggests that the said
      association is not largely due to the confounding effects of lung cancer. 

PMID- 24014253
TI  - Size-controlled soft-template synthesis of carbon nanodots toward versatile
      photoactive materials.
AB  - Size-controlled soft-template synthesis of carbon nanodots (CNDs) as novel
      photoactive materials is reported. The size of the CNDs can be controlled by
      regulating the amount of an emulsifier. As the size increases, the CNDs exhibit
      blue-shifted photoluminescence (PL) or so-called an inverse PL shift. Using time
      correlated single photon counting, ultraviolet photoelectron spectroscopy, and
      low-temperature PL measurements, it is revealed that the CNDs are composed of sp2
      clusters with certain energy gaps and their oleylamine ligands act as auxochromes
      to reduce the energy gaps. This insight can provide a plausible explanation on
      the origin of the inverse PL shift which has been debatable over a past decade.
      To explore the potential of the CNDs as photoactive materials, several prototypes
      of CND-based optoelectronic devices, including multicolored light-emitting diodes
      and air-stable organic solar cells, are demonstrated. This study could shed light
      on future applications of the CNDs and further expedite the development of other
      related fields.

PMID- 24014254
TI  - C-PHIS: a concept map-based knowledge base framework to develop personal health
      information systems.
AB  - In this paper we describe the development of a Personal Health Information System
      using a knowledge base developed using concept maps. Here we describe a solution
      for providing the critical need to develop an information capturing system that
      helps domain experts in developing a graphical representation of the
      aforementioned knowledge base which can then be converted to a machine-actable
      form of information. A prototype application has been developed using this
      information capturing system that clearly demonstrates the use of the knowledge
      base framework using concept maps to develop Personal Health Information System
      for lung cancer patients. 

PMID- 24014255
TI  - Development and evaluation of tools for measuring the quality of experience (QoE)
      in mHealth applications.
AB  - The rapid spread of smartphones and tablets in the last years has created a new
      software industry whose fast growth has propitiated numerous low-quality
      applications to be revised and improved. The main aim of this paper is to develop
      a tool to assess the Quality of Experience (QoE) of mobile Health (mHealth)
      applications in order to improve the quality of the existing apps and the ones to
      be released. Firstly, a review of the applications of mHealth has been done in
      order to obtain a general classification. Secondly, the tool for measuring the
      QoE is developed in the form of a survey with the help of psychologists. Finally,
      this tool is evaluated using a sample of applications selected with the aid of
      the classification obtained. A survey with 21 questions using the Likert scale
      and destined to users has been successfully created, and its evaluation has been
      positive, resulting in a good method for measuring the QoE of the different
      features that the applications in the field of health care usually have. The tool
      created can be very useful for developers in order to assess the quality of their
      health care apps, indicating their positive aspects and the ones which must be
      revised and improved, avoiding the releasing of low-quality apps. 

PMID- 24014257
TI  - Application of Analyte Harvesting Nanoparticle Technology to the Measurement of
      Urinary HGH in Healthy Individuals.
AB  - Urine represents a valuable biofluid for noninvasive measurement of Human Growth
      Hormone (HGH) secretion. Unfortunately, currently available commercial HGH
      immunoassays do not achieve the sensitivity needed for urinary HGH measurement in
      the low picogram per milliliter range, the expected normal concentration range of
      HGH in urine. A nanotechnology based sample preprocessing step was used to
      extract and concentrate HGH in urine so that urinary HGH could be measured with a
      clinical grade standard immunoassay designed for serum (Immulite 1000, Siemens).
      We applied the nanoparticle enhanced immunoassay to evaluate the baseline value
      of urinary HGH in a population of healthy young adults (age 18-30, N=33, median
      21, M: F=39%:61%, with no reported medical therapies). Nanoparticle sample
      preprocessing effectively improved the lower limit of detection of the Immulite
      HGH assay by more than 50 fold, shifting the linear range of the assay to
      encompass the expected value of urinary HGH. The full process between run and
      within run CV% was 7.9 and 9.0%, respectively. On 33 healthy volunteers, the 95%
      reference values for hGH in spot urine normalized to specific gravity were 0.64 -
      16.85 pg/mL (0.05-5.82 ng/g creatinine). Nanoparticle preprocessing constitutes a
      reliable means of measuring urinary HGH with a clinical grade immunoassay, now
      establishing a normal baseline value for HGH in urine. Nanoparticles can be used
      to study the kinetics of HGH excretion in urine, and the factors that influence
      urinary HGH secretion and HGH isoform proportions.

PMID- 24014256
TI  - Top 10 clinical research developments in antiphospholipid syndrome.
AB  - Persistently positive antiphospholipid antibodies (aPL) with thrombosis and/or
      pregnancy morbidity are a characteristic of antiphospholipid syndrome (APS).
      Although many challenges and controversies exist regarding APS diagnosis and
      management, there has been significant progress in APS clinical research in
      parallel with increased understanding of the pathogenesis. The purpose of this
      review is to discuss the "top ten" recent clinical developments in APS, including
      the magnitude of the problem, standardization of aPL tests, predictors of
      clinical events, diagnostic algorithms, new clinical research collaboration, and
      potential future treatments, e.g., new anticoagulants and immunosuppressive
      agents. 

PMID- 24014258
TI  - Bifurcation study of a neural field competition model with an application to
      perceptual switching in motion integration.
AB  - Perceptual multistability is a phenomenon in which alternate interpretations of a
      fixed stimulus are perceived intermittently. Although correlates between activity
      in specific cortical areas and perception have been found, the complex patterns
      of activity and the underlying mechanisms that gate multistable perception are
      little understood. Here, we present a neural field competition model in which
      competing states are represented in a continuous feature space. Bifurcation
      analysis is used to describe the different types of complex spatio-temporal
      dynamics produced by the model in terms of several parameters and for different
      inputs. The dynamics of the model was then compared to human perception
      investigated psychophysically during long presentations of an ambiguous,
      multistable motion pattern known as the barberpole illusion. In order to do this,
      the model is operated in a parameter range where known physiological response
      properties are reproduced whilst also working close to bifurcation. The model
      accounts for characteristic behaviour from the psychophysical experiments in
      terms of the type of switching observed and changes in the rate of switching with
      respect to contrast. In this way, the modelling study sheds light on the
      underlying mechanisms that drive perceptual switching in different contrast
      regimes. The general approach presented is applicable to a broad range of
      perceptual competition problems in which spatial interactions play a role. 

PMID- 24014259
TI  - Psychopathological similarities and differences between obese patients seeking
      surgical and non-surgical overweight treatments.
AB  - PURPOSE: To compare the psychopathological characteristics of obese patients
      seeking bariatric surgery with those seeking a medical approach. METHODS: A total
      of 394 consecutive outpatients seeking bariatric surgery were compared with 683
      outpatients seeking a medical treatment. All patients were referred to the same
      institution. RESULTS: Obesity surgery patients reported higher body mass index
      (BMI), objective/subjective binging and more severe general psychopathology,
      while obesity medical patients showed more eating and body shape concerns.
      Depression was associated with higher BMI among obesity surgery clinic patients,
      whereas eating-specific psychopathology was associated with higher BMI and
      objective binge-eating frequency among obesity medical clinic patients.
      CONCLUSIONS: Patients seeking bariatric surgery showed different
      psychopathological features compared with those seeking a non-surgical approach.
      This suggests the importance for clinicians to consider that patients could seek
      bariatric surgery on the basis of the severity of the psychological distress
      associated with their morbid obesity, rather than criteria only based on clinical
      indication.

PMID- 24014260
TI  - Neuropsychological variables and clinical status in anorexia nervosa:
      relationship between visuospatial memory and central coherence and eating
      disorder symptom severity.
AB  - AIM: To explore the relationship between visuospatial memory, weak central
      coherence, and eating disorder (ED) symptoms in anorexia nervosa (AN) inpatients.
      SAMPLE: 31 female AN inpatients. METHODS: Rey complex figure test (RCFT) was used
      to assess both visuospatial memory and central coherence. RCFT consisted of copy
      and recall trials. ED symptoms were assessed by The Eating Disorder Examination
      Questionnaire (EDE-Q) and The Clinical and Research Inventory for Eating
      Disorders (CR-EAT). RESULTS: We found a statistically significant negative
      correlation between recall accuracy and the total EDE-Q score. Furthermore,
      recall accuracy and recall central coherence significantly negatively correlate
      with several EDE-Q and CR-EAT scales. CONCLUSIONS: These findings may contribute
      to a better understanding of cognitive impairments specifically in ED, and to
      refining interventions aiming at their improvement.

PMID- 24014262
TI  - Melt infiltration: an emerging technique for the preparation of novel functional
      nanostructured materials.
AB  - The rapidly expanding toolbox for design and preparation is a major driving force
      for the advances in nanomaterials science and technology. Melt infiltration
      originates from the field of ceramic nanomaterials and is based on the
      infiltration of porous matrices with the melt of an active phase or precursor. In
      recent years, it has become a technique for the preparation of advanced
      materials: nanocomposites, pore-confined nanoparticles, ordered mesoporous and
      nanostructured materials. Although certain restrictions apply, mostly related to
      the melting behavior of the infiltrate and its interaction with the matrix, this
      review illustrates that it is applicable to a wide range of materials, including
      metals, polymers, ceramics, and metal hydrides and oxides. Melt infiltration
      provides an alternative to classical gas-phase and solution-based preparation
      methods, facilitating in several cases extended control over the nanostructure of
      the materials. This review starts with a concise discussion on the physical and
      chemical principles for melt infiltration, and the practical aspects. In the
      second part of this contribution, specific examples are discussed of
      nanostructured functional materials with applications in energy storage and
      conversion, catalysis, and as optical and structural materials and emerging
      materials with interesting new physical and chemical properties. Melt
      infiltration is a useful preparation route for material scientists from different
      fields, and we hope this review may inspire the search and discovery of novel
      nanostructured materials. 

PMID- 24014261
TI  - Roles of adenosine A1 and A2A receptors in the control of micturition in rats.
AB  - AIMS: Adenosine is a neurotransmitter that exerts numerous physiological effects
      in many organs. However, few studies have focused on the role of adenosine
      receptors in the control of micturition. Therefore, we examined the role of
      adenosine A1 and A2A receptors in the control of bladder activity in rats with
      normal or acetic acid (AA) irritated bladders. METHODS: Cystometrograms during
      saline or 0.2% AA infusion were recorded under urethane anesthesia in female
      Sprague-Dawley rats. After a stabilization period, CCPA (A1 receptor agonist)
      and/or ZM24138 (A2A receptor antagonist) were administered intravenously (i.v.),
      intrathecally (i.t.), intracerebroventricularly (i.c.v.), or intravesically.
      Micturition parameters were recorded and compared before and after drug
      administration. RESULTS: I.v., i.t., or i.c.v. administration of CCPA or ZM24138
      significantly increased intercontraction intervals (ICIs) in both saline and AA
      infusion groups. During AA infusion, the inhibitory effects induced by i.c.v.
      CCPA or i.t. ZM24138 were significantly greater than those by i.t. or i.c.v.
      administration, respectively. Intravesical administration of CCPA, but not
      ZM24138, significantly increased ICI. CONCLUSIONS: These results indicated that:
      (1) when nociceptive signals from the bladder increase, adenosine A1 receptor
      mediated inhibition of micturition is enhanced in the brain, compared to the
      normal condition, (2) A1 receptor activation also exerts a peripheral inhibitory
      effect on micturition, and (3) adenosine A2A receptor-mediated excitatory
      mechanisms are enhanced in the spinal cord following C-fiber bladder afferent
      stimulation. Thus adenosine A1 receptor agonists and A2A receptor antagonists
      might be effective for the treatment of overactive bladder and/or bladder
      hypersensitive disorders, in which C-fiber afferent function is enhanced.

PMID- 24014263
TI  - Nocturnal enuresis in sickle cell disease and thalassemia major: associated
      factors in a clinical sample.
AB  - In this study, we aimed to investigate the prevalence and associated factors of
      nocturnal enuresis in sickle cell disease (SCD) and thalassemia major (TM)
      patients in a single center from Turkey. One hundred and six patients, 51 (48.1
      %) with TM and 55 (51.9 %) with SCD, and 80 age-matched healthy controls were
      included in the study. Semi-structured interviews were conducted with the
      caregivers of pediatric and adult patients. The interview included questions on
      nocturnal enuresis and psychosocial variables. Patients' hospital files were
      reviewed to search for disease-related factors. Twenty-eight of the patients
      (26.4 %) and three (3.7 %) of the controls had nocturnal enuresis. Younger age,
      TM diagnosis, family history of nocturnal enuresis and family problems were found
      to be more frequent in patients with nocturnal enuresis. Among the patients with
      SCD, frequencies of hospitalization and painful crises were found to be higher in
      those with enuresis. According to the binary logistic regression analysis,
      diagnosis of TM (p = 0.031, OR = 0.262) and younger age (p = 0.005, OR = 0.869)
      were found to be independent risk factors for nocturnal enuresis in the patient
      group. Nocturnal enuresis is a common problem in children and young adults with
      TM and SCD. Associated factors in both conditions will be clarified with future
      studies.

PMID- 24014264
TI  - Urinary 6-sulphatoxymelatonin levels and sleep disorders in children with
      migraine.
AB  - We conducted the present study to assess melatonin secretion in a sample of
      children with migraine, to describe their sleep patterns and problems, and to
      examine the impact of sleep problems on migraine disability. The parents of 18
      children with migraine completed the Children's Sleep Habits Questionnaire and
      Pediatric Migraine Disability Assessment Score in Arabic. The parents of 18
      healthy controls also completed the Children's Sleep Habits Questionnaire.
      Urinary 6-sulphatoxymelatonin levels were determined with the enzyme-linked
      immunosorbent assay method. There was no significant difference in urinary 6
      sulphatoxymelatonin between the migraine and control groups (Z = -0.127, P =
      .889). There were no significant differences between groups in Children's Sleep
      Habits Questionnaire subscales or total scores. There were significant
      correlations between bedtime resistance, parasomnias subscales, and migraine
      disability. Our findings indicate that nocturnal production of melatonin is not
      reduced in children with migraine, and sleep disturbances impact the degree of
      migraine disability. 

PMID- 24014265
TI  - Copper-catalyzed domino cycloaddition/C-N coupling/cyclization/(C-H arylation):
      an efficient three-component synthesis of nitrogen polyheterocycles.
AB  - A cat of all trades: A single copper catalyst promoted up to three reaction steps
      with separate catalytic cycles in a domino sequence (azide-alkyne
      cycloaddition/Goldberg amidation/Camps cyclization/(C?H arylation)) for the rapid
      construction of complex heterocycles from three simple components under mild
      conditions. Facile cleavage of the triazole ring enables further elaboration of
      the condensation products. 

PMID- 24014266
TI  - The role of privacy protection in healthcare information systems adoption.
AB  - Privacy protection is an important issue and challenge in healthcare information
      systems (HISs). Recently, some privacy-enhanced HISs are proposed. Users' privacy
      perception, intention, and attitude might affect the adoption of such systems.
      This paper aims to propose a privacy-enhanced HIS framework and investigate the
      role of privacy protection in HISs adoption. In the proposed framework, privacy
      protection, access control, and secure transmission modules are designed to
      enhance the privacy protection of a HIS. An experimental privacy-enhanced HIS is
      also implemented. Furthermore, we proposed a research model extending the unified
      theory of acceptance and use of technology by considering perceived security and
      information security literacy and then investigate user adoption of a privacy
      enhanced HIS. The experimental results and analyses showed that user adoption of
      a privacy-enhanced HIS is directly affected by social influence, performance
      expectancy, facilitating conditions, and perceived security. Perceived security
      has a mediating effect between information security literacy and user adoption.
      This study proposes several implications for research and practice to improve
      designing, development, and promotion of a good healthcare information system
      with privacy protection. 

PMID- 24014267
TI  - Letter to the editor: Staphylococcus aureus screening and decolonization in
      orthopaedic surgery and reduction of surgical site infections.

PMID- 24014268
TI  - CORR Insights (r): Does vitamin D improve osteoarthritis of the knee: a
      randomized controlled pilot trial.

PMID- 24014269
TI  - Ipsilateral proximal femur and shaft fractures treated with hip screws and a
      reamed retrograde intramedullary nail.
AB  - BACKGROUND: Although not common, proximal femoral fractures associated with
      ipsilateral shaft fractures present a difficult management problem. A variety of
      surgical options have been employed with varying results. QUESTIONS/PURPOSES: We
      investigated the use of hip screws and a reamed retrograde intramedullary (IM)
      nail for the treatment of this combined fracture pattern in terms of
      postoperative alignment (malunion), nonunion, and complications. METHODS: Between
      May 2002 and October 2011, a total of 95 proximal femoral fractures with
      associated shaft fractures were treated at three participating Level 1 trauma
      centers; all were treated with hip screw fixation (cannulated screws or sliding
      hip screws) and retrograde reamed IM nails. The medical records of these patients
      were reviewed retrospectively for alignment, malunion, nonunion, and
      complications. Followup was available on 92 of 95 (97%) of the patients treated
      with hip screws and a retrograde nail. Forty were treated with a sliding hip
      screw, and 52 were treated with cannulated screws. RESULTS: There were five
      proximal malunions in this series (5%). The union rate was 98% (90 of 92) for the
      femoral neck fractures and 91.3% (84 of 92) for the femoral shaft fractures after
      the initial surgery. There were two nonunions of comminuted femoral neck
      fractures after cannulated screw fixation. There was no difference in femoral
      neck union or alignment when comparing cannulated screws to a sliding hip screw.
      Four open comminuted femoral shaft fractures went on to nonunion and required
      secondary surgery to obtain union, and one patient developed symptomatic
      avascular necrosis. CONCLUSIONS: The treatment of ipsilateral proximal femoral
      neck and shaft fractures with hip screw fixation and a reamed retrograde nail
      demonstrated a high likelihood of union for the femoral neck fractures and a low
      risk of malunion. Comminution and initial displacement of the proximal femoral
      fracture may still lead to a small incidence of malunion or nonunion, and open
      comminuted femoral shaft fractures still may progress to nonunion despite
      appropriate surgical management. LEVEL OF EVIDENCE: Level IV, therapeutic study.
      See Instructions for Authors for a complete description of levels of evidence.

PMID- 24014270
TI  - CORR Insights (r): Abbreviated psychologic questionnaires are valid in patients
      with hand conditions.

PMID- 24014272
TI  - Reply to the Letter to the editor: Femoroacetabular impingement predisposes to
      traumatic posterior hip dislocation.

PMID- 24014273
TI  - Medieval monastic mortality: hazard analysis of mortality differences between
      monastic and nonmonastic cemeteries in England.
AB  - Scholarship on life in medieval European monasteries has revealed a variety of
      factors that potentially affected mortality in these communities. Though there is
      some evidence based on age-at-death distributions from England that monastic
      males lived longer than members of the general public, what is missing from the
      literature is an explicit examination of how the risks of mortality within
      medieval monastic settings differed from those within contemporaneous lay
      populations. This study examines differences in the hazard of mortality for adult
      males between monastic cemeteries (n = 528) and non-monastic cemeteries (n = 368)
      from London, all of which date to between AD 1050 and 1540. Age-at-death data
      from all cemeteries are pooled to estimate the Gompertz hazard of mortality, and
      "monastic" (i.e., buried in a monastic cemetery) is modeled as a covariate
      affecting this baseline hazard. The estimated effect of the monastic covariate is
      negative, suggesting that individuals in the monastic communities faced reduced
      risks of dying compared to their peers in the lay communities. These results
      suggest better diets, the positive health benefits of religious behavior, better
      living conditions in general in monasteries, or selective recruitment of healthy
      or higher socioeconomic status individuals.

PMID- 24014275
TI  - A ratiometric probe composed of an anionic conjugated polyelectrolyte and a
      cationic phosphorescent iridium(III) complex for time-resolved detection of
      Hg(II) in aqueous media.
AB  - A hybrid complex composed of an anionic conjugated polyelectrolyte (PFB-SO3Na)
      and a cationic phosphorescent Ir(III) oligomer is formed through electrostatic
      interaction by simple physical mixing in aqueous media. Due to their opposite
      charges and their effective spectral overlap, fluorescence resonance energy
      transfer occurs from the blue-emissive PFB-SO3Na to the red-emissive
      phosphorescent Ir(III) complex, which allows ratiometric and colorimetric Hg(2+)
      sensing in aqueous solution with good selectivity, sensitivity, as well as
      visible detection. Time-resolved photoluminescence is applied for Hg(2+)
      detection, which can effectively eliminate the background interference and
      improve the sensing sensitivity and signal-to-noise ratio in complicated media.

PMID- 24014274
TI  - Transforming growth factor-beta (TGF-beta) expression is increased in the
      subsynovial connective tissues of patients with idiopathic carpal tunnel
      syndrome.
AB  - Non-inflammatory fibrosis of the subsynovial connective tissue (SSCT) is a
      hallmark of carpal tunnel syndrome (CTS). The etiology of this finding and its
      relationship to the development of CTS remain poorly understood. Recent studies
      have found that transforming growth factor-beta (TGF-beta) plays a central role
      in fibrosis. The purpose of this study was to investigate the expression of TGF
      beta and connective tissue growth factor (CTGF), a downstream mediator of TGF
      beta, in the pathogenesis of CTS. We compared SSCT specimens from 26 idiopathic
      CTS patients with specimens from 10 human cadaver controls with no previous
      diagnosis of CTS. Immunohistochemistry was performed to determine levels TGF
      beta1, CTGF, collagen 1(Col1) and collagen 3 (Col3) expression. TGF-beta1 (p <
      0.01), CTGF (p < 0.01), and Col3 (p < 0.01) were increased in SSCT of CTS
      patients compared with control tissue. In addition, a strong positive correlation
      was found between TGF-beta1 and CTGF, (R(2) = 0.80, p < 0.01) and a moderate
      positive correlation between Col3 and TGF-beta1 (R(2) = 0.49, p < 0.01). These
      finding suggest that there is an increased expression of TGF-beta and CTGF, a TGF
      beta regulated protein, and that this TGF-beta activation may be responsible for
      SSCT fibrosis in CTS patients.

PMID- 24014277
TI  - Photo-roll lithography (PRL) for continuous and scalable patterning with
      application in flexible electronics.
AB  - A novel nanofabrication methodology for continuous, scalable, and geometry
      tunable lithography is developed, named photo-roll lithography (PRL), by
      integrating photolithography with rollable processing. As a flexible mask
      attached to a quartz cylinder containing a UV source rolls over a
      photoresistcoated substrate, PRL realizes continuous photolithographic
      fabrication of various micro/nanoscale patterns with geometry that is tunable by
      controlling mask-substrate motions. 

PMID- 24014276
TI  - Optimism and survival: does an optimistic outlook predict better survival at
      advanced ages? A twelve-year follow-up of Danish nonagenarians.
AB  - BACKGROUND AND AIMS: Studies examining predictors of survival among the oldest
      old have primarily focused on objective measures, such as physical function and
      health status. Only a few studies have examined the effect of personality traits
      on survival, such as optimism. The aim of this study was to examine whether an
      optimistic outlook predicts survival among the oldest-old. METHODS: The Danish
      1905 Cohort Survey is a nationwide, longitudinal survey comprising all
      individuals born in Denmark in 1905. At baseline in 1998, a total of 2,262
      persons aged 92 or 93 agreed to participate in the intake survey. The baseline in
      person interview consisted of a comprehensive questionnaire including physical
      functioning and health, and a question about whether the respondent had an
      optimistic, neutral or pessimistic outlook on his or her own future. RESULTS:
      During the follow-up period of 12 years (1998-2010) there were 2,239 deaths (99
      %) in the 1905 Cohort Survey. Univariable analyses revealed that optimistic women
      and men were at lower risk of death compared to their neutral counterparts [HR
      0.82, 95 % CI (0.73-0.93) and 0.81, 95 % CI (0.66-0.99), respectively]. When
      confounding factors such as baseline physical and cognitive functioning and
      disease were taken into account the association between optimism and survival
      weakened in both sexes, but the general pattern persisted. Optimistic women were
      still at lower risk of death compared to neutral women [HR 0.85, 95 % CI (0.74
      0.97)]. The risk of death was also decreased for optimistic men compared to their
      neutral counterparts, but the effect was non-significant [HR 0.91, 95 % CI (0.73
      1.13)]. CONCLUSION: An optimistic outlook appears to be a significant predictor
      of survival among the oldest-old women. It may also be a significant predictor
      for men but the sample size is small.

PMID- 24014278
TI  - Structure-based functional site recognition for p21-activated kinase 4.
AB  - Recently, many molecular modeling methods are being developed to better
      understand the principles underlying protein folding. In the present study, fully
      flexible dinucleotides d(pApA), d(pApC), d(pApG), d(pApT), d(pCpA), d(pCpC),
      d(pCpG), d(pCpT), d(pGpA), d(pGpC), d(pGpG), d(pGpT), d(pTpA), d(pTpC), d(pTpG)
      and d(pTpT) were docked onto the surface of p21-activated kinase 4 (PAK4) kinase
      domain. The results showed that automated docking was a useful tool to identify
      the functional sites of PAK4 and it may provide a theoretical basis for the
      interaction data obtained from previous experiments. Therefore, structure-based
      docking with fully flexible dinucleotide probes might be a good tool to predict
      and annotate the functional sites of enzymes. 

PMID- 24014279
TI  - Reciprocal ECG change in reperfused ST-elevation myocardial infarction is
      associated with myocardial salvage and area at risk assessed by cardiovascular
      magnetic resonance.
AB  - OBJECTIVE: ST-elevation acute myocardial infarction (STEMI) is frequently
      associated with reciprocal ST depression in contralateral ECG leads. The
      relevance of these changes is debated. This study examined whether reciprocal ECG
      changes in STEMI reflect larger myocardial area at risk (AAR) and/or infarct
      size. DESIGN: Patients were stratified by presence of reciprocal change on the
      presenting ECG, defined as >= 1 mm ST depression in >= 2 inferior leads for
      anterior STEMI, or >= 2 anterior leads for inferior STEMI. Infarcted tissue was
      defined on late enhancement and AAR on T2-weighted cardiovascular magnetic
      resonance (CMR). SETTING: Patients with reperfused first STEMI underwent CMR
      within 3 days of presentation. MAIN OUTCOME MEASURES: In addition to AAR and
      infarct mass, myocardial salvage was calculated as (AAR mass-infarct mass) and
      salvage index as myocardial salvage/AAR mass. RESULTS: Thirty-five patients were
      analysed (n=35). Patients with reciprocal ECG changes (n=19) had higher AAR mass
      than those without (42 g vs 29 g, p<0.001), and higher myocardial salvage (27 g
      vs 9 g, p<0.001) and myocardial salvage index (61% vs 17%, p<0.001) but similar
      infarct size (16 g vs 20 g, p=0.3) and ejection fraction (43% vs 45%, p=0.5).
      CONCLUSIONS: STEMI patients with reciprocal ECG changes have larger AAR, higher
      myocardial salvage and salvage index than those without. Reciprocal changes
      appear to be a marker of increased ischaemic myocardium at risk and indicate the
      potential for increased salvage with emergency revascularisation. Reciprocal
      changes showed no relationship to infarct size, which may be influenced by
      ischaemia time and other treatment factors.

PMID- 24014280
TI  - Global left ventricular longitudinal systolic strain as a major predictor of
      cardiovascular events in patients with atrial fibrillation.
AB  - OBJECTIVE: Although global left ventricular longitudinal systolic strain (GLS) is
      a sensitive measure of left ventricular mechanics, its relationship with adverse
      cardiovascular (CV) events in atrial fibrillation (AF) has not been evaluated.
      This study sought to examine the ability of GLS in predicting CV events in AF.
      DESIGN: Observational cohort study. SETTING: Department of cardiology in a
      university hospital. PATIENTS: 196 persistent AF patients referred for
      echocardiographic examination. MAIN OUTCOME MEASURES: The risk of GLS measured by
      index beat method for CV events was assessed by Cox proportional hazards
      analyses. CV events were defined as CV death, non-fatal stroke and
      hospitalisation for heart failure. RESULTS: There were 19 CV deaths, 12 non-fatal
      stroke and 28 hospitalisations for heart failure during an average follow-up of
      21 +/- 10 months. Multivariate analysis showed worsening GLS (HR 1.121; 95% CI
      1.023 to 1.228, p=0.014) was independently associated with increased CV events.
      In direct comparison, GLS outperformed left ventricular ejection fraction (LVEF)
      and systolic mitral annulus velocity (Sa) in predicting adverse CV events both in
      univariate and multivariate models (p <= 0.043). Besides, the addition of GLS to
      a Cox model containing chronic heart failure, hypertension, age >= 75 years,
      diabetes, prior stroke score, estimated glomerular filtration rate, LVEF and Sa
      provided an additional benefit in the prediction of adverse CV events (p=0.022).
      CONCLUSIONS: GLS was a major parameter and stronger than LVEF and Sa in
      predicting adverse CV events and could offer an additional prognostic benefit
      over conventional clinical and echocardiographic systolic parameters in AF.

PMID- 24014281
TI  - Tumour necrosis factor-alpha antagonism: a potential therapeutic target for
      prevention of arrhythmogenesis in the setting of acute myocardial infarction?

PMID- 24014282
TI  - Atrial fibrillation and thromboembolism in patients with hypertrophic
      cardiomyopathy: systematic review.
AB  - CONTEXT: HCM is commonly associated with AF. Current guidelines for AF management
      omit detailed advice for HCM because of a lack of clinical prediction tools that
      estimate the risk of developing AF and an absence of adequately powered treatment
      studies. OBJECTIVE: To critically review current literature on atrial
      fibrillation (AF) and thromboembolism in hypertrophic cardiomyopathy (HCM) and
      meta-analyse prevalence and incidence. DATA SOURCES: PubMed and Web of Science.
      STUDY SELECTION: Studies investigating AF and stroke in HCM as primary or
      secondary endpoint. DATA EXTRACTION: Two investigators independently reviewed and
      extracted data from the identified articles. A random effect meta-regression
      model and I(2) statistics were used for analysis. RESULTS: A population of 7381
      patients (33 studies) revealed overall AF prevalence of 22.45% (95% CI 20.13% to
      24.77%), I(2)=78.9% (p<0.001). Overall prevalence of thromboembolism in HCM
      patients with AF was 27.09% (95% CI 20.94% to 33.25%), I(2)=61.4% ( p<0.01).
      Overall AF incidence was 3.08% per 100 patients per year (95% CI 2.63% to 3.54%,
      I(2)=86.5%, p<0.001) and incidence of thromboembolism in HCM patients with AF was
      3.75% per 100 patients per year (95% CI 2.88% to 4.61%), I(2)=37.9% (p=0.1). Left
      atrial (LA) dimension and age were common predictors for AF and thromboembolism.
      Meta-analysis revealed an LA diameter of 38.03 mm (95% CI 34.62% to 41.44%) in
      sinus rhythm and 45.37 mm (95% CI 41.64% to 49.04%) in AF. There were no
      randomised controlled trials of therapy; anticoagulation was associated with
      lower stroke incidence but data on other interventions were limited and
      contradictory. CONCLUSIONS: AF is common in HCM and associated with high
      thromboembolic risk. LA dimension and age are independently associated with AF
      but the literature is insufficient to create robust clinical tools to predict AF
      or thromboembolism. Most data suggest that AF patients should be anticoagulated.

PMID- 24014283
TI  - The author's reply.

PMID- 24014284
TI  - The association between plasma homocysteine and coronary heart disease is
      modified by the MTHFR 677C>T polymorphism.
AB  - OBJECTIVE: An elevated level of total plasma homocysteine (tHcy) has been
      associated with risk of coronary heart disease (CHD). The level of tHcy is
      affected by lifestyle, in addition to genetic predisposition. The methylene
      tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the
      strongest genetic predictors of tHcy. We examined whether the association between
      tHcy and CHD is modified by the MTHFR 677C>T polymorphism. DESIGN AND SETTING:
      Data from two case-control studies of first-time myocardial infarction (MI),
      Stockholm Heart Epidemiology Programme (SHEEP), and for MI and unstable angina,
      INTERGENE, were analysed in parallel. PATIENTS: THcy was determined in a total of
      1150 cases and 1753 controls. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The
      outcome comprised first-time MI and unstable angina, subsumed as CHD. Logistic
      regression was used to investigate the association between tHcy and CHD, and its
      modification by genotype. RESULTS: High tHcy was confirmed to be a risk factor
      for CHD in both studies. In SHEEP, the association between tHcy and MI was
      observed in MTHFR 677 C-homozygotes (OR=1.4, 95% CI 1.2 to 1.6, for a difference
      by 1 SD of log tHcy) and in heterozygotes (OR=1.3, 95% CI 1.1 to 1.6) but not in
      T-homozygotes, independent of smoking, physical activity and obesity. An effect
      modification of similar magnitude was observed but not statistically significant
      in the smaller INTERGENE study, and confirmed in a meta-analysis of both studies.
      CONCLUSIONS: Two Swedish case-control studies showed that the association between
      elevated tHcy and CHD was confined to carriers of the MTHFR 677 C-allele, which
      could have implications for the efficiency of tHcy-lowering treatment.

PMID- 24014285
TI  - Bias attenuation results for nondifferentially mismeasured ordinal and coarsened
      confounders.
AB  - Suppose we are interested in the effect of a binary treatment on an outcome where
      that relationship is confounded by an ordinal confounder. We assume that the true
      confounder is not observed, rather we observe a nondifferentially mismeasured
      version of it. We show that under certain monotonicity assumptions about its
      effect on the treatment and on the outcome, an effect measure controlling for the
      mismeasured confounder will fall between its corresponding crude and the true
      effect measures. We present results for coarsened, and, under further
      assumptions, for multiple misclassified confounders.

PMID- 24014286
TI  - Surgical hip dislocation for treatment of femoroacetabular impingement: factors
      predicting 5-year survivorship.
AB  - BACKGROUND: Patients with femoroacetabular impingement (FAI) often develop pain,
      impaired function, and progression of osteoarthritis (OA); this is commonly
      treated using surgical hip dislocation, femoral neck and acetabular rim
      osteoplasty, and labral reattachment. However, results with these approaches, in
      particular risk factors for OA progression and conversion to THA, have varied.
      QUESTIONS/PURPOSES: We asked if patients undergoing surgical hip dislocation with
      labral reattachment to treat FAI experienced (1) improved hip pain and function;
      and (2) prevention of OA progression; we then determined (3) the survival of the
      hip at 5-year followup with the end points defined as the need for conversion to
      THA, progression of OA by at least one Tonnis grade, and/or a Merle d'Aubigne
      Postel score less than 15; and calculated (4) factors predicting these end
      points. METHODS: Between July 2001 and March 2003, we performed 146 of these
      procedures in 121 patients. After excluding 35 patients (37 hips) who had prior
      open surgery and 11 patients (12 hips) who had a diagnosis of Perthes disease,
      this study evaluated the 75 patients (97 hips, 66% of the procedures we performed
      during that time) who had a mean followup of 6 years (range, 5-7 years). We used
      the anterior impingement test to assess pain, the Merle d'Aubigne-Postel score to
      assess function, and the Tonnis grade to assess OA. Survival and predictive
      factors were calculated using the method of Kaplan and Meier and Cox regression,
      respectively. RESULTS: The proportion of patients with anterior impingement
      decreased from 95% to 17% (p < 0.001); the Merle d'Aubigne-Postel score improved
      from a mean of 15 to 17 (p < 0.001). Seven hips (7%) showed progression of OA and
      another seven hips (7%) converted to THA Survival free from any end point (THA,
      progression of OA, or a Merle d'Aubigne-Postel < 15) of well-functioning joints
      at 5 years was 91%; and excessive acetabular rim trimming, preoperative OA,
      increased age at operation, and weight were predictive factors for the end
      points. CONCLUSIONS: At 5-year followup, 91% of patients with FAI treated with
      surgical hip dislocation, osteoplasty, and labral reattachment showed no THA,
      progression of OA, or an insufficient clinical result, but excessive acetabular
      trimming, OA, increased age, and weight were associated with early failure. To
      prevent early deterioration of the joint, excessive rim trimming or trimming of
      borderline dysplastic hips has to be avoided.

PMID- 24014288
TI  - A spatiotemporal view of plasmid loss in biofilms and planktonic cultures.
AB  - This Commentary by Madsen, Burmolle, and Sorensen discusses the article Non
      invasive in situ monitoring and quantification of TOL plasmid segregational loss
      within Pseudomonas putida biofilms by Ma, Katzenmeyer, and Bryers. (2013.
      Biotechnol Bioeng. 110(11):2949-2958. DOI: 10.1002/bit.24953).

PMID- 24014287
TI  - Copper(II)-bis-histidine coordination structure in a fibrillar amyloid beta
      peptide fragment and model complexes revealed by electron spin echo envelope
      modulation spectroscopy.
AB  - Truncated and mutated amyloid-beta (Abeta) peptides are models for systematic
      study-in homogeneous preparations-of the molecular origins of metal ion effects
      on Abeta aggregation rates, types of aggregate structures formed, and
      cytotoxicity. The 3D geometry of bis-histidine imidazole coordination of Cu(II)
      in fibrils of the nonapetide acetyl-Abeta(13-21)H14A has been determined by
      powder (14) N electron spin echo envelope modulation (ESEEM) spectroscopy. The
      method of simulation of the anisotropic combination modulation is described and
      benchmarked for a Cu(II) -bis-cis-imidazole complex of known structure. The
      revealed bis-cis coordination mode, and the mutual orientation of the imidazole
      rings, for Cu(II) in Ac-Abeta(13-21)H14A fibrils are consistent with the proposed
      beta-sheet structural model and pairwise peptide interaction with Cu(II) , with
      an alternating [-metal-vacancy-]n pattern, along the N-terminal edge. Metal
      coordination does not significantly distort the intra-beta-strand peptide
      interactions, which provides a possible explanation for the acceleration of Ac
      Abeta(13-21)H14A fibrillization by Cu(II) , through stabilization of the
      associated state and low-reorganization integration of beta-strand peptide pair
      precursors. 

PMID- 24014290
TI  - B cell receptor and antigens in CLL.
AB  - Nowadays, chronic lymphocytic leukemia (CLL) is considered as a prototypic
      antigen-driven lymphoma, with antigenic stimuli from the microenvironment
      promoting tumor outgrowth. Antigen recognition is a function of both the
      clonotypic B cell receptor immunoglobulin (BcR IG) and various other immune
      sensors, e.g., the Toll-like receptors. The critical role of BcR IG-mediated
      signaling in CLL development and evolution is underscored by the following: the
      disease-biased IG gene repertoire; the subdivision of CLL based on the somatic
      hypermutation load of the BcR IG into two broad categories with vastly different
      prognosis and eventual outcome; the existence of subsets of cases with distinct,
      quasi-identical (stereotyped) BcR IGs; and the clinical efficacy of novel
      therapeutics inhibiting BcR signaling. Here, we trace the immunogenetic evidence
      for antigen selection in CLL and also consider the types of implicated antigens
      as well as the immune signaling pathways relevant for CLL ontogeny and clonal
      progression. 

PMID- 24014289
TI  - Alteration of the microRNA network during the progression of Alzheimer's disease.
AB  - An overview of miRNAs altered in Alzheimer's disease (AD) was established by
      profiling the hippocampus of a cohort of 41 late-onset AD (LOAD) patients and 23
      controls, showing deregulation of 35 miRNAs. Profiling of miRNAs in the
      prefrontal cortex of a second independent cohort of 49 patients grouped by Braak
      stages revealed 41 deregulated miRNAs. We focused on miR-132-3p which is strongly
      altered in both brain areas. Downregulation of this miRNA occurs already at Braak
      stages III and IV, before loss of neuron-specific miRNAs. Next-generation
      sequencing confirmed a strong decrease of miR-132-3p and of three family-related
      miRNAs encoded by the same miRNA cluster on chromosome 17. Deregulation of miR
      132-3p in AD brain appears to occur mainly in neurons displaying Tau hyper
      phosphorylation. We provide evidence that miR-132-3p may contribute to disease
      progression through aberrant regulation of mRNA targets in the Tau network. The
      transcription factor (TF) FOXO1a appears to be a key target of miR-132-3p in this
      pathway. 

PMID- 24014291
TI  - The CLL cell microenvironment.
AB  - Cross talk between CLL cells and accessory stromal cells in specialized tissue
      microenvironments, such as the secondary lymphoid organs, favors CLL progression
      by promoting malignant B cell growth and drug resistance. Disrupting the cross
      talk between CLL cells and their milieu is an attractive, novel strategy for
      treating CLL patients. This chapter summarizes current knowledge about cellular
      and molecular interactions between CLL cells and their supportive tissue
      microenvironment and the therapeutic targets that are emerging, focusing on the
      CXCR4-CXCL12 axis and small molecule inhibitors that are targeting the B cell
      receptor-associated kinases SYK, BTK, and PI3Kdelta. Clinically relevant aspects
      of these new therapeutics will be discussed, along with an outlook into future
      biologically oriented therapeutic strategies. The rapid progress in dissecting
      the CLL microenvironment and the promising early results of these new targeted
      treatments in CLL indicate that CLL has become a role model for microenvironment
      dependent cancers. 

PMID- 24014292
TI  - Acquired genomic copy number aberrations in CLL.
AB  - Approximately 80 % of chronic lymphocytic leukemia (CLL) carries somatically
      acquired genomic copy number aberrations (aCNAs). These include gains of entire
      chromosomes (trisomy 12) and recurrent genomic losses, including interstitial
      deletions of various lengths at 13q14, 11q, and of more uniform length at 17p. In
      addition, approximately 10-15 second-tier aCNAs, with frequencies of 1-5 %, have
      been identified. In this chapter, we will discuss the biology and clinical
      significance of these CLL-associated aCNAs in detail and also discuss generic
      aspects of aCNAs relevant to all cancer cells. The hypothesis is advanced that
      most if not all aCNAs in CLL deregulate multiple target genes as a consequence of
      aCNA-associated gene mutations and through stable deregulation of gene
      expression. The concept of elevated genomic complexity (multiple aCNAs per CLL
      case) is reinforced as one of the strongest biological traits associated with
      aggressive CLL with short survival. Further, all inherited polymorphic copy
      number variations as detected through SNP 6.0 array profiling of T-cell-derived
      DNA of 255 CLL patients are listed to allow the reader a more critical appraisal
      of the somatic status of CLL-associated aCNAs as reported in the literature.
      Finally, given that aCNAs and gene mutations coexist in many CLL cells, we stress
      the importance of understanding in detail the relative biological and clinical
      roles each mutation type serves in individual CLL patients; this is a research
      area in need of more in-depth investigation. 

PMID- 24014293
TI  - Recurrent gene mutations in CLL.
AB  - Next-generation sequencing of whole genomes and exomes in chronic lymphocytic
      leukemia (CLL) has provided the first comprehensive view of somatic mutations in
      this disease. Subsequent studies have characterized the oncogenic pathways and
      clinical implications of a number of these mutations. The global number of
      somatic mutations per case is lower than those described in solid tumors but is
      in agreement with previous estimates of less than one mutation per megabase in
      hematological neoplasms. The number and pattern of somatic mutations differ in
      tumors with unmutated and mutated IGHV, extending at the genomic level the
      clinical differences observed in these two CLL subtypes. One of the striking
      conclusions of these studies has been the marked genetic heterogeneity of the
      disease, with a relatively large number of genes recurrently mutated at low
      frequency and only a few genes mutated in up to 10-15 % of the patients. The
      mutated genes tend to cluster in different pathways that include NOTCH1
      signaling, RNA splicing and processing machinery, innate inflammatory response,
      Wnt signaling, and DNA damage and cell cycle control, among others. These results
      highlight the molecular heterogeneity of CLL and may provide new biomarkers and
      potential therapeutic targets for the diagnosis and management of the disease. 

PMID- 24014294
TI  - TP53 aberrations in chronic lymphocytic leukemia.
AB  - CLL patients harboring TP53 defects remain the most challenging group in terms of
      designing rational and effective therapy. Irrespective of the treatment employed
      chemotherapy, chemoimmunotherapy, or pure biological drugs-median survival of
      these patients does not exceed 3-4 years. This adverse outcome is caused by a
      less effective response to therapeutics acting through DNA damage induction and
      relying on the subsequent initiation of apoptosis as well as by virtually
      inevitable aggressive relapse. Patient proportions with TP53 defects at diagnosis
      or before first therapy were reported within the range 5-15 %, but they increase
      dramatically in pretreated cohorts (reported up to 44 %), and also in patients
      with Richter transformation (50 % harbor TP53 defects). Currently, most
      laboratories monitor TP53 defect as presence of 17p deletion using I-FISH, but 23
      45 % of TP53-affected patients were shown to harbor only mutation(s). In other
      patients with intact TP53, the p53 pathway may be impaired by mutations in ATM
      gene coding for the p53-regulatory kinase; however, prognosis of ATM-defective
      patients is not as poor as those with TP53 abnormalities. Though many novel
      agents are under development, the monoclonal antibody alemtuzumab and allogeneic
      stem cell transplantation remain the basic treatment options for TP53-affected
      CLL patients. 

PMID- 24014295
TI  - Gene expression and epigenetic deregulation.
AB  - The last decade resulted in many scientific discoveries illuminating epigenetic
      mechanisms of gene regulation and genome organization. DNA methylation emerged as
      playing a pivotal role in development and cancer. Genome-wide changes in DNA
      methylation, including hypermethylation of tumor suppressor genes and genome-wide
      loss of methylation, are two dominant mechanisms that deregulate gene expression
      and contribute to chromosomal instability. In this chapter we give an overview of
      how methylation patterns are established during B-cell development and what
      machinery is necessary to maintain those patterns. We summarize the current state
      of knowledge of aberrant changes taking place during and contributing to lymphoid
      transformation in general and to the development of CLL in particular. We discuss
      key deregulated biomarkers extensively studied using single-gene approaches and
      give an overview of a wealth of data that became available from genome-wide
      approaches, focusing on pathways that are critical for lymphomagenesis. We also
      highlight epigenetic differences between known prognostic groups of CLL. 

PMID- 24014296
TI  - Apoptosis deregulation in CLL.
AB  - The description of apoptosis and the identification of the genes that regulate it
      have proved pivotal to our understanding of how cancer cells accumulate and
      ultimately cause morbidity and mortality. It has become increasingly clear that
      in CLL the balance between the pro- and anti-apoptotic members of the BCL2 family
      of apoptotic regulatory proteins is critical in the development and clinical
      progression of CLL. Furthermore, the apoptotic potential of the CLL cell
      determines chemotherapy sensitivity and ultimately progression-free and overall
      survival. The unravelling of the BCL2 story in CLL has led to the development of
      a whole new class of therapeutic agents-the BH3 mimetics-which are significantly
      more targeted than conventional chemo-immunotherapy and therefore promise potent
      clinical activity coupled with reduced toxicity. 

PMID- 24014297
TI  - Richter syndrome.
AB  - Transformation of chronic lymphocytic leukemia (CLL) to aggressive lymphoma is
      known as Richter syndrome (RS). In the CLL population considered as a whole, the
      prevalence of RS development ranges from 2 to 7 %. The most common pathologic
      phenotype at the time of RS transformation is diffuse large B-cell lymphoma
      (DLBCL), while, in a small fraction of cases, the transformed phase shows
      pathologic features mimicking Hodgkin lymphoma. TP53 disruption and MYC
      activation cooperate as dual hits in driving DLBCL transformation. Two biomarkers
      (NOTCH1 mutations and usage of the immunoglobulin VH CDR3 subset 8) may help in
      identifying CLL patients at risk of DLBCL transformation to be considered for
      close monitoring and a careful biopsy policy. In the presence of clinical
      features suspicious of RS, diagnosis of transformation and choice of the site of
      biopsy may take advantage of (18)FDG PET/CT. The prognosis of RS transformation
      is generally highly unfavorable. However, the pattern of survival is not
      homogeneous and may be predicted on clinical and biological grounds. RS that are
      clonally unrelated to the paired CLL phase are biologically and clinically
      different from clonally related cases, and should be considered, and probably
      managed, as a de novo DLBCL arising in the context of CLL. Rituximab-containing
      polychemotherapy represents the backbone for induction treatment in patients with
      clonally related DLBCL transformation. Younger patients who respond to induction
      therapy should be offered stem cell transplant to prolong survival. 

PMID- 24014298
TI  - Molecular biomarkers in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western
      World and remains incurable with conventional chemotherapy treatment approaches.
      CLL has a highly varied clinical course. The substantial clinical variability in
      the clinical course of CLL has motivated intense efforts at identifying molecular
      markers that can be used for CLL prognostication. While many such markers have
      been proposed, few have stood the test of time; this is due to various reasons
      outlined in detail in this chapter.Of the reasons that have affected the
      usefulness and broad applicability of CLL biomarkers a few stand out as
      recurrent: lack of independent effects of individual markers on prognosis; the
      use of arbitrary cutoffs when using continuous variables; technical challenges in
      validity, reproducibility, and reliability (classical test characteristics); and
      lack of marker validation in prospectively identified CLL patient
      cohorts.Nonetheless, a few useful prognostic markers (CLL interphase FISH,
      immunoglobulin heavy chain variable region mutation status) have been identified,
      and others are still in transition to widespread clinical applications (TP53
      mutations, SNP array-based elevated genomic complexity).As CLL therapy
      transitions from genotoxic combination therapies to targeted therapies, it will
      be of importance to reestablish the usefulness of our current understanding of
      individual CLL traits in CLL prognosis. Finally, the identification of predictive
      markers remains important given the established associations of poor response
      rates with shortened survival and the ongoing need for more personalized
      approaches in CLL management. 

PMID- 24014300
TI  - Immunotherapies in CLL.
AB  - Chronic lymphocytic leukemia (CLL) is the most frequently diagnosed leukemia in
      the Western world, yet remains essentially incurable. Although initial
      chemotherapy response rates are high, patients invariably relapse and
      subsequently develop resistance to chemotherapy. For the moment, allogeneic
      hematopoietic stem cell transplant (allo-HSCT) remains the only potentially
      curative treatment for patients with CLL, but it is associated with high rates of
      treatment-related mortality. Immune-based treatment strategies to augment the
      cytotoxic potential of T cells offer exciting new treatment options for patients
      with CLL, and provide a unique and powerful spectrum of tools distinct from
      traditional chemotherapy. Among the most novel and promising of these approaches
      are chimeric antigen receptor (CAR)-based cell therapies that combine advances in
      genetic engineering and adoptive immunotherapy. 

PMID- 24014301
TI  - Towards targeted therapy of chronic lymphocytic leukemia.
AB  - The B cell antigen receptor (BCR) and its downstream pathways are pivotal in the
      pathogenesis of chronic lymphocytic leukemia (CLL). Recently, inhibitors of
      kinases in the BCR pathway have shown promising clinical activity in CLL. Based
      upon these results, the treatment paradigm for CLL will likely undergo major
      changes. The kinases essential for BCR signal transduction, which are emerging as
      targets for CLL treatment, and the specific inhibitors under development are the
      focus of this chapter. In particular, the BTK inhibitor ibrutinib and the PI3K
      inhibitor idelalisib (GS-1101) are two evolving targeted therapies with the most
      mature clinical data. 

PMID- 24014302
TI  - Inherited susceptibility to CLL.
AB  - Chronic lymphocytic leukaemia (CLL) is the most common lymphoid malignancy in
      Western countries, accounting for around a quarter of all leukaemias. Despite a
      strong familial basis to CLL, with risks in first-degree relatives of CLL cases
      being increased around sevenfold, the inherited genetic basis of CLL is currently
      largely unknown. The failure of genetic studies of CLL families to provide
      support for a major disease-causing locus has suggested a model of susceptibility
      based on the co-inheritance of multiple low-risk variants, some of which will be
      common. Recent genome-wide association studies of CLL have vindicated this model
      of inherited susceptibility to CLL, identifying common variants at multiple
      independent loci influencing risk. Here we review the evidence for inherited
      genetic predisposition to CLL and what the currently identified risk loci are
      telling us about the biology of CLL development. 

PMID- 24014299
TI  - Critical signal transduction pathways in CLL.
AB  - Receptor tyrosine kinases (RTKs) are cell-surface transmembrane receptors that
      contain regulated kinase activity within their cytoplasmic domain and play a
      critical role in signal transduction in both normal and malignant cells. Besides
      B cell receptor (BCR) signaling in chronic lymphocytic leukemia (CLL), multiple
      RTKs have been reported to be constitutively active in CLL B cells, resulting in
      enhanced survival and resistance to apoptosis of the leukemic cells induced by
      chemotherapeutic agents. In addition to increased plasma levels of various types
      of cytokines/growth factors in CLL, we and others have detected that CLL B cells
      spontaneously produce multiple cytokines in vitro which may constitute an
      autocrine loop of RTK activation on the leukemic B cells. Moreover, aberrant
      expression and activation of non-RTKs, for example, Src/Syk kinases, induce
      resistance of the leukemic B cells to therapy. Based on current available
      knowledge, we detailed the impact of aberrant activities of various RTKs/non-RTKs
      on CLL B cell survival and the potential of using these signaling components as
      future therapeutic targets in CLL therapy. 

PMID- 24014305
TI  - Phenolic compounds with IL-6 inhibitory activity from Aster yomena.
AB  - A new biflavonoid, named asteryomenin (1), as well as six known phenolic
      compounds, esculetin (2), 4-O-beta-D-glucopyranoside-3-hydroxy methyl benzoate
      (3), caffeic acid (4), isoquercitrin (5), isorhamnetin-3-O-glucoside (6), and
      apigenin (7) were isolated from the aerial parts of Aster yomena. The structures
      of compounds (1-7) were identified based on 1D and 2D NMR, including (1)H-(1)H
      COSY, HSQC, HMBC and NOESY spectroscopic analyses. Compounds 2-7 were isolated
      from this plant for the first time. For these isolates, the inhibitory activity
      of IL-6 production in the TNF-alpha stimulated MG-63 cell was examined. Among
      these isolates, compounds 4 and 7 appeared to have potent inhibitory activity of
      IL-6 production in the TNF-alpha stimulated MG-63 cell, while compounds 1-3 and 5
      6 showed moderate activity. 

PMID- 24014306
TI  - Anti-adipogenic activity of the edible brown alga Ecklonia stolonifera and its
      constituent fucosterol in 3T3-L1 adipocytes.
AB  - Fucosterol is a sterol metabolite of brown algae and regulates genes involved
      with cholesterol homeostasis. As a part of our continuous search for anti-obesity
      agents from natural marine sources, the anti-adipogenic activities of Ecklonia
      stolonifera and its sterol, fucosterol, were evaluated for the inhibition of
      adipocyte differentiation and lipid formation. Oil Red O staining was used to
      evaluate triglyceride contents in 3T3-L1 pre-adipocytes primed by differentiation
      medium (DM) I and DM II. The methanolic extract of E. stolonifera showed strong
      anti-adipogenic activity, and was thus fractionated with several solvents. Among
      the tested fractions, the dichloromethane (CH2Cl2) fraction was found to be the
      most active fraction, with significant inhibition (40.5 %) of intracellular lipid
      accumulation at a non-toxic concentration, followed by the ethyl acetate fraction
      (30.2 %) at the same concentration, while the n-butanol and water fractions did
      not show inhibitory activity within the tested concentrations. The strong anti
      adipogenic CH2Cl2-soluble fraction was further purified by a repeated
      chromatography to yield fucosterol. Fucosterol reduced lipid contents in a
      concentration-dependent manner without showing any cytotoxicity. Fucosterol
      treatment also yielded a decrease in the expression of the adipocyte marker
      proteins peroxisome proliferator-activated receptor gamma (PPARgamma) and
      CCAAT/enhancer-binding protein alpha (C/EBPalpha) in a concentration-dependent
      manner. Taken together, these results suggest that fucosterol inhibits expression
      of PPARgamma and C/EBPalpha, resulting in a decrease of lipid accumulation in 3T3
      L1 pre-adipocytes, indicating that the potential use of E. stolonifera and its
      bioactive fucosterol as an anti-obesity agent.

PMID- 24014307
TI  - A new neolignan and lignans from the stems of Lindera obtusiloba Blume and their
      anti-allergic inflammatory effects.
AB  - A new neolignan, linderin A (1), together with six known lignans, (+)-xanthoxyol
      (2), pluviatilol (3), actiforin (4), (+)-syringaresinol (5), (+)-(7S,8R,8'R)
      acuminatolide (6), and (+)-9'-O-trans-feruloyl-5,5'-dimethoxylariciresinol (7)
      were isolated from the stems of Lindera obtusiloba Blume (Lauraceae). Their
      chemical structures were elucidated by a combination of spectroscopic analysis
      and chemical reaction, and the absolute configuration of 1 was determined by
      Mosher's esterification. The effect of compounds 1-7 on tumor necrosis factor
      (TNF)-alpha, interleukin(IL)-6, and their inhibitory activity of histamine
      release were examined using human mast cells. Among the lignans tested, compounds
      1, 3, 4, 6, and 7 inhibited release of histamine from mast cells. Especially,
      compounds 1 and 4 suppressed the gene expressions of pro-inflammatory cytokines,
      TNF-alpha, and IL-6 in human mast cells. Our findings suggest that the lignan
      constituents in L. obtusiloba may contribute to its anti-allergic inflammatory
      effects. 

PMID- 24014303
TI  - miR deregulation in CLL.
AB  - B-cell chronic lymphocytic leukemia (CLL) is the most frequent human leukemia and
      it occurs in two forms, indolent and aggressive. Although clinical features and
      genetic abnormalities in CLL are well documented, molecular details underlying
      the disease are still under investigation.MicroRNAs are small noncoding RNAs
      involved in a variety of cellular processes and expressed in a tissue-specific
      manner. MicroRNAs have the ability to regulate gene expression. In physiological
      conditions, microRNAs act as gene expression controllers by targeting the mRNA or
      inhibiting its translation. Their deregulation can lead to an alteration of the
      expression level of many genes which can induce the development or promote the
      progression of tumors.In CLL, microRNAs can function as oncogenes, tumor
      suppressor genes, and/or can be used as markers for disease onset/progression.
      For example, in indolent CLL, 13q14 deletions targeting miR-15/16 initiate the
      disease, while in aggressive CLL miR-181 targets the critical TCL1 oncogene and
      can also be used as a progression marker.Here we discuss the foremost findings
      about the role of microRNAs in CLL pathogenesis, and how this knowledge can be
      used to identify new approaches to treat CLL. 

PMID- 24014308
TI  - Spinal reconstruction for osteomyelitis with free vascularized fibular grafts
      using intra-abdominal recipient vessels: A series of three cases.
AB  - Reconstruction of bony defects in the surgical management of vertebral
      osteomyelitis is a challenging endeavor. Our objective is to report the use of
      intra-abdominal vessels as the recipient vessels for microanastomosis of
      vascularized bone graft and the use of a spinal cage for fixation. Three patients
      failed conservative treatment for vertebral osteomyelitis and suffered pathologic
      fracture. Their treatment consisted of staged posterior irrigation and
      debridement with segmental fixation, followed by a thoracoabdominal approach
      multiple-level corpectomy. Reconstruction was performed with a free vascularized
      fibular graft placed within a custom, expandable cage. The vascularized fibular
      graft was anastomosed to an intra-abdominal recipient vessel. All patients
      improved clinically with no neurologic deficits noted. All showed evidence of
      successful fusion. Free vascularized bone grafts continue to be an excellent
      option for multi-level spinal defects related to osteomyelitis. Intra-abdominal
      recipient vessels are appropriate recipient vessels, as their diameter, length,
      and accessibility allow vascularized bone graft reconstruction of vertebral
      column defects of the thoracolumbar region. These vessels are also easily
      accessible and the anastomoses can be performed in the superficial operating
      incision.

PMID- 24014310
TI  - Determining the role of matrix compliance in the differentiation of mammary stem
      cells.
AB  - Multipotent stem cells maintain the structure and function of the mammary gland
      throughout its development and respond to the physiological demands associated
      with pregnancy and lactation. The ability of mammary stem cells to maintain
      themselves as well as to give rise to differentiated progeny is not only affected
      by soluble factors but has increasingly become linked to mechanical cues
      including the elastic modulus of the extracellular matrix (ECM). Here we describe
      a protocol for determining how the mechanical properties of the ECM regulate the
      fate of mammary stem or progenitor cells. This protocol includes detailed methods
      for the fabrication of substrata with varying stiffness, culture of mammary
      progenitor cells on synthetic substrata, pharmacological modulation of actomyosin
      contractility, and analysis of gene expression to define the resulting fate of
      human mammary stem cells. 

PMID- 24014309
TI  - Parents' nonstandard work schedules and child well-being: a critical review of
      the literature.
AB  - This paper provides a comprehensive review of empirical evidence linking parental
      nonstandard work schedules to four main child developmental outcomes:
      internalizing and externalizing problems, cognitive development, and body mass
      index. We evaluated the studies based on theory and methodological rigor
      (longitudinal data, representative samples, consideration of selection and
      information bias, confounders, moderators, and mediators). Of 23 studies
      published between 1980 and 2012 that met the selection criteria, 21 reported
      significant associations between nonstandard work schedules and an adverse child
      developmental outcome. The associations were partially mediated through parental
      depressive symptoms, low quality parenting, reduced parent-child interaction and
      closeness, and a less supportive home environment. These associations were more
      pronounced in disadvantaged families and when parents worked such schedules full
      time. We discuss the nuance, strengths, and limitations of the existing studies,
      and propose recommendations for future research. 

PMID- 24014311
TI  - Conjugation of proteins to polymer chains to create multivalent molecules.
AB  - The activation of cellular signaling cascades, critical for regulating cell
      function and fate, often involves changes in the organization of receptors in the
      cell membrane. Using synthetic multivalent ligands to control the nanoscale
      organization of cellular receptors into clusters is an attractive approach to
      elicit desired downstream cellular responses, since multivalent ligands can be
      significantly more potent than their corresponding monovalent ligands. Synthetic
      multivalent ligands can serve as both versatile biological tools and potent
      nanoscale therapeutics, for example in applications to harness them to control
      stem cell fate in vitro and in vivo. Here we describe the use of recombinant
      protein expression and bioconjugate chemistry to synthesize multivalent ligands
      that have the potential to regulate cell signaling in a variety of cell types. 

PMID- 24014312
TI  - Bioreactor cultivation of anatomically shaped human bone grafts.
AB  - In this chapter, we describe a method for engineering bone grafts in vitro with
      the specific geometry of the temporomandibular joint (TMJ) condyle. The
      anatomical geometry of the bone grafts was segmented from computed tomography
      (CT) scans, converted to G-code, and used to machine decellularized trabecular
      bone scaffolds into the identical shape of the condyle. These scaffolds were
      seeded with human bone marrow-derived mesenchymal stem cells (MSCs) using spinner
      flasks and cultivated for up to 5 weeks in vitro using a custom-designed
      perfusion bioreactor system. The flow patterns through the complex geometry were
      modeled using the FloWorks module of SolidWorks to optimize bioreactor design.
      The perfused scaffolds exhibited significantly higher cellular content, better
      matrix production, and increased bone mineral deposition relative to non-perfused
      (static) controls after 5 weeks of in vitro cultivation. This technology is
      broadly applicable for creating patient-specific bone grafts of varying shapes
      and sizes.

PMID- 24014313
TI  - The multivalent effect in glycosidase inhibition: probing the influence of
      valency, peripheral ligand structure, and topology with cyclodextrin-based
      iminosugar click clusters.
AB  - In view of recent reports of a strong multivalent effect in glycosidase
      inhibition, a library of beta-CD-based multivalent iminosugars has been
      efficiently synthesized by way of Cu(I) -catalyzed azide-alkyne cycloaddition
      (CuAAC). In combination with the first application of isothermal titration
      calorimetry (ITC) experiments to the study of multivalent iminosugar-enzyme
      interactions, the inhibition properties of these click clusters were evaluated on
      a panel of glycosidases. The structural parameters that were varied include
      valency, peripheral ligand structure, and topology. The inhibition results
      obtained with the iminosugar clusters further highlight the importance of
      multivalency in the inhibition of alpha-mannosidase. Generally, the evaluated
      multivalent iminosugars displayed comparable thermodynamic signatures of binding
      towards alpha-mannosidase (Jack bean): that is, large negative enthalpies of
      complexation coupled with small entropies of either sign. In addition, the
      enthalpy-entropy compensation observed in all tested cases may be attributed to a
      common mechanism of dissociation for the enzyme-multivalent iminosugar
      interactions. The measured binding stoichiometries indicated that each iminosugar
      cluster interacts with no more than one protein molecule. 

PMID- 24014314
TI  - A short-read multiplex sequencing method for reliable, cost-effective and high
      throughput genotyping in large-scale studies.
AB  - Accurate genotyping is important for genetic testing. Sanger sequencing-based
      typing is the gold standard for genotyping, but it has been underused, due to its
      high cost and low throughput. In contrast, short-read sequencing provides
      inexpensive and high-throughput sequencing, holding great promise for reaching
      the goal of cost-effective and high-throughput genotyping. However, the short
      read length and the paucity of appropriate genotyping methods, pose a major
      challenge. Here, we present RCHSBT-reliable, cost-effective and high-throughput
      sequence based typing pipeline-which takes short sequence reads as input, but
      uses a unique variant calling, haploid sequence assembling algorithm, can
      accurately genotype with greater effective length per amplicon than even Sanger
      sequencing reads. The RCHSBT method was tested for the human MHC loci HLA-A, HLA
      B, HLA-C, HLA-DQB1, and HLA-DRB1, upon 96 samples using Illumina PE 150 reads.
      Amplicons as long as 950 bp were readily genotyped, achieving 100% typing
      concordance between RCHSBT-called genotypes and genotypes previously called by
      Sanger sequence. Genotyping throughput was increased over 10 times, and cost was
      reduced over five times, for RCHSBT as compared with Sanger sequence genotyping.
      We thus demonstrate RCHSBT to be a genotyping method comparable to Sanger
      sequencing-based typing in quality, while being more cost-effective, and higher
      throughput. 

PMID- 24014315
TI  - Do we need another Kt/V?

PMID- 24014316
TI  - Nrf2 implicated as a novel therapeutic target for renal regeneration after acute
      kidney injury.

PMID- 24014319
TI  - Reply: To PMID 21248295.

PMID- 24014321
TI  - MR image reconstruction based on framelets and nonlocal total variation using
      split Bregman method.
AB  - PURPOSE: An efficient algorithm for magnetic resonance (MR) image reconstruction
      is needed, especially when sparse sampling is employed to accelerate data
      acquisition. The aim of this paper is to solve the sparse MRI problem based on
      nonlocal total variation (NLTV) and framelet sparsity using the split Bregman
      algorithm. A new method was developed and tested in a variety of MR image
      acquisitions. METHODS: The proposed method minimizes a linear combination of
      NLTV, least square data fitting and framelet terms to reconstruct the MR images
      from undersampled k-space data. The NLTV and framelet sparsity are taken as the
      L1-regularization functional and solved by using the split Bregman method.
      Experiments were conducted to compare the proposed algorithm with several
      different reconstruction methods, including the operator splitting algorithm,
      variable splitting method, composite splitting algorithm and its accelerated
      version called the fast composite splitting algorithm. A detailed evaluation
      study was done on the reconstruction of MR images which represent varying degrees
      of object structural complexity. Both qualitative visualization-based and
      quantitative metric-based evaluations were done. RESULTS: Numerical results on
      various data corresponding to different sampling rates showed the advantages of
      the new method in preserving geometrical features, textures and fine structures.
      The proposed algorithm was compared with previous methods in terms of the
      reconstruction accuracy and computational complexity with favorable results.
      CONCLUSION: An efficient new algorithm was developed for compressed MR image
      reconstruction based on NLTV and framelet sparsity. The algorithm effectively
      solves a hybrid regularizer based on framelet sparsity and NLTV using the split
      Bregman method. NLTV makes the recovered image quality sharper by preserving the
      edges or boundaries more accurately, and framelets often improve image quality.
      The comparison with alternative method yielded results that demonstrate the
      superiority of the proposed algorithm for compressed MR image reconstruction.

PMID- 24014323
TI  - Ion-pairing of phosphonium salts in solution: C-H???halogen and C-H???pi hydrogen
      bonds.
AB  - The (1) H NMR chemical shifts of the C(alpha)?H protons of arylmethyl
      triphenylphosphonium ions in CD2 Cl2 solution strongly depend on the
      counteranions X(-) . The values for the benzhydryl derivatives Ph2 CH?PPh3 (+) 
      X(-) , for example, range from deltaH =8.25 (X(-) =Cl(-) ) over 6.23 (X(-) =BF4 (
      ) ) to 5.72 ppm (X(-) =BPh4 (-) ). Similar, albeit weaker, counterion-induced
      shifts are observed for the ortho-protons of all aryl groups. Concentration
      dependent NMR studies show that the large shifts result from the deshielding of
      the protons by the anions, which decreases in the order Cl(-) > Br(-) ? BF4 (-) >
      SbF6 (-) . For the less bulky derivatives PhCH2 ?PPh3 (+)  X(-) , we also find
      C?H???Ph interactions between C(alpha)?H and a phenyl group of the BPh4 (-)
      anion, which result in upfield NMR chemical shifts of the C(alpha)?H protons.
      These interactions could also be observed in crystals of (p-CF3 -C6 H4 )CH2 ?PPh3
      (+)  BPh4 (-) . However, the dominant effects causing the counterion-induced
      shifts in the NMR spectra are the C?H???X(-) hydrogen bonds between the
      phosphonium ion and anions, in particular Cl(-) or Br(-) . This observation
      contradicts earlier interpretations which assigned these shifts predominantly to
      the ring current of the BPh4 (-) anions. The concentration dependence of the (1)
      H NMR chemical shifts allowed us to determine the dissociation constants of the
      phosphonium salts in CD2 Cl2 solution. The cation-anion interactions increase
      with the acidity of the C(alpha)?H protons and the basicity of the anion. The
      existence of C?H???X(-) hydrogen bonds between the cations and anions is
      confirmed by quantum chemical calculations of the ion pair structures, as well as
      by X-ray analyses of the crystals. The IR spectra of the Cl(-) and Br(-) salts in
      CD2 Cl2 solution show strong red-shifts of the C?H stretch bands. The C?H stretch
      bands of the tetrafluoroborate salt PhCH2 ?PPh3 (+)  BF4 (-) in CD2 Cl2 ,
      however, show a blue-shift compared to the corresponding BPh4 (-) salt. 

PMID- 24014320
TI  - Pathological impact of SMN2 mis-splicing in adult SMA mice.
AB  - Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading
      genetic cause of infant mortality. The related SMN2 gene expresses suboptimal
      levels of functional SMN protein, due to a splicing defect. Many SMA patients
      reach adulthood, and there is also adult-onset (type IV) SMA. There is currently
      no animal model for adult-onset SMA, and the tissue-specific pathogenesis of post
      developmental SMN deficiency remains elusive. Here, we use an antisense
      oligonucleotide (ASO) to exacerbate SMN2 mis-splicing. Intracerebroventricular
      ASO injection in adult SMN2-transgenic mice phenocopies key aspects of adult
      onset SMA, including delayed-onset motor dysfunction and relevant
      histopathological features. SMN2 mis-splicing increases during late-stage
      disease, likely accelerating disease progression. Systemic ASO injection in adult
      mice causes peripheral SMN2 mis-splicing and affects prognosis, eliciting marked
      liver and heart pathologies, with decreased IGF1 levels. ASO dose-response and
      time-course studies suggest that only moderate SMN levels are required in the
      adult central nervous system, and treatment with a splicing-correcting ASO shows
      a broad therapeutic time window. We describe distinctive pathological features of
      adult-onset and early-onset SMA. 

PMID- 24014322
TI  - Surgical process modelling: a review.
AB  - PURPOSE: Surgery is continuously subject to technological and medical innovations
      that are transforming daily surgical routines. In order to gain a better
      understanding and description of surgeries, the field of surgical process
      modelling (SPM) has recently emerged. The challenge is to support surgery through
      the quantitative analysis and understanding of operating room activities. Related
      surgical process models can then be introduced into a new generation of computer
      assisted surgery systems. METHODS: In this paper, we present a review of the
      literature dealing with SPM. This methodological review was obtained from a
      search using Google Scholar on the specific keywords: "surgical process
      analysis", "surgical process model" and "surgical workflow analysis". RESULTS:
      This paper gives an overview of current approaches in the field that study the
      procedural aspects of surgery. We propose a classification of the domain that
      helps to summarise and describe the most important components of each paper we
      have reviewed, i.e., acquisition, modelling, analysis, application and
      validation/evaluation. These five aspects are presented independently along with
      an exhaustive list of their possible instantiations taken from the studied
      publications. CONCLUSION: This review allows a greater understanding of the SPM
      field to be gained and introduces future related prospects.

PMID- 24014324
TI  - Pituitary apoplexy initially mistaken for bacterial meningitis.
AB  - We presented a case of a 62-year-old man whose initial clinical picture was
      suggestive of bacterial meningitis, but instead had pituitary apoplexy. We
      highlighted how pituitary apoplexy can mimic bacterial meningitis, learning
      points on how clinical assessment can aid earlier diagnosis and the importance of
      considering this differential diagnosis, particularly with the associated
      morbidity and mortality if missed.

PMID- 24014325
TI  - A newborn internal and external malformations.

PMID- 24014326
TI  - Rickets in the tropics: not always nutritional.

PMID- 24014327
TI  - Uncontrolled hyperglycaemia: a reversible cause of hemichorea-hemiballismus.
AB  - Hyperosmolar hyperglycaemic state (HHS) an acute complication of diabetes
      mellitus, can be associated with neurological involvement ranging from seizures,
      involuntary movements to reversible focal neurological deficits without any
      structural lesions. We report a 71-year-old woman, a known case of type 2
      diabetes mellitus who presented with the sudden onset of hemichorea
      hemiballismus. On investigations she had hyperglycaemia and urinary tract
      infection. Achievement of euglycemia with insulin therapy resolved the
      involuntary movements completely. This highlights the fact that HHS is an
      uncommon but easily treatable cause of recent onset unilateral hemichorea
      hemiballismus.

PMID- 24014328
TI  - Cryptococcal lymphadenitis: an unusual initial presentation of HIV infection.
AB  - Lymphadenopathy can occur at any stage of HIV infection, with multiple
      aetiologies including reactive, infectious and malignant. An accurate and timely
      diagnosis has obvious implications for treatment. We report cryptococcal
      lymphadenitis as the presenting manifestation of HIV infection. The diagnosis in
      our patient was eventually confirmed with a lymph node biopsy. Fine needle
      aspiration cytology has been shown to be a rapid and cost-effective method, which
      has been used in the diagnosis of lymphadenopathy in HIV infection, and could
      have been used to make an earlier diagnosis in our patient.

PMID- 24014329
TI  - Small bowel evisceration through the anus in rectal prolapse in an Indian male
      patient.
AB  - Evisceration of small intestine through anus is a rare presentation in emergency.
      We reported a case with long history of recurrent complete rectal prolapse
      presenting in emergency as small bowel protruding out through anal orifice. The
      small bowel herniated out from a spontaneous perforation in rectosigmoid. After
      resuscitation, emergency exploratory laparotomy was carried out and small bowel
      was reposited in the peritoneal cavity through the site of perforation by pulling
      and pushing maneuvere and the perforated segment of rectosigmoid was exteriorised
      as double barrel colostomy.

PMID- 24014330
TI  - An unusual recurrence of dysembroplastic neuroepithelial tumours after a seizure
      free period of 8 years.
AB  - Dysembryoplastic neuroepithelial tumours (DNETs) are grade 1 central nervous
      tumours, which can be diagnosed judiciously based on clinical features and
      radiological investigations, having a good prognosis after surgical resection.
      However, the recurrence of tumours due to variable epileptic zones leading to
      persistence of seizures can make the management of such cases challenging. We
      present a case of DNET where the patient had recurrence of the tumour with
      worsening of seizure activity 8 years after initial surgical resection.

PMID- 24014331
TI  - Infiltrating angiolipoma of the cheek.
AB  - Angiolipoma, spindle cell lipoma, myelolipoma, chondrolipoma and myxolipoma are
      histological variants of lipomas arising from fat tissue. Although angiolipoma is
      the most common tumour in the trunk and forearm, it occurs infrequently in the
      head and neck region. In this report we present a case of angiolipoma occurring
      in the buccal mucosa of a 33-year-old man. The patient had noticed a painless
      mass in his buccal mucosa for 2 months. The surgically removed tumour, measuring
      4 * 4 cm in diameter was histologically evaluated. The tumour was composed of
      proliferations of mature fat cells and connective tissue containing many small
      blood vessels, which were evenly distributed.

PMID- 24014332
TI  - Atypical features in a patient with acute promyelocytic leukaemia: a potential
      diagnostic pitfall.
AB  - Acute promyelocytic leukaemia (APML) is a malignancy with a high cure rate;
      however, delay in diagnosis or treatment can result in morbidity and mortality.
      APML has characteristic clinical, morphological, immunophenotypic and molecular
      features. In patients with acute leukaemia, a high index of suspicion is required
      to exclude APML. Very rarely APML patients at diagnosis can demonstrate atypical
      features. We reported a patient whose bone marrow features resembled acute
      myeloid leukaemia with predominantly agranular blasts, devoid of Auer rods and
      expressing CD34 and HLA-DR on flow cytometry. APML was not suspected initially
      but after cytogenetic and molecular genetic studies demonstrated t(15;17),
      appropriate therapy with ATRA+ chemotherapy was instituted and the patient showed
      remarkable and sustained response to treatment. This case highlights the fact
      that morphology and immunophenotyping are useful but not infallible indicators
      for these malignancies and, ultimate diagnoses will require detection of the
      characteristic molecular markers.

PMID- 24014333
TI  - Intravitreal bevacizumab as an adjunct in the management of a vascular choroidal
      granuloma.
AB  - A 43-year-old woman with tubercular choroidal granuloma showed poor response to
      conventional first-line four-drug antitubercular therapy (ATT) and
      corticosteroids. A therapeutic trial with intravitreal bevacizumab (1.25 mg in
      0.05 mL) injections as an adjunct to ATT and corticosteroids led to a prompt
      initial regression of granuloma with restoration of visual acuity that was
      sustained for almost 2 years. A subsequent recurrence of the same lesion with
      evidence of enhanced vascularity was treated with intravitreal bevacizumab alone,
      that led to a complete regression of the granuloma with no recurrence until 1
      year of follow-up.

PMID- 24014334
TI  - Osteoma of temporomandibular joint: a rarity.
AB  - Osteoma is a benign tumour consisting of mature bone tissue. It is an uncommon
      lesion that occurs in the bones of the craniofacial complex. Only a few cases
      involving the temporomandibular joint have been reported. An osteoma of the left
      temporomandibular joint causing limited mouth opening in a 22-year-old man with
      CT findings revealing the unusual possibility in differential diagnosis of
      trismus.

PMID- 24014335
TI  - Actinomycosis mimicking sinonasal malignant disease.

PMID- 24014336
TI  - Primary colorectal non-Hodgkin's lymphoma in a retropositive patient.
AB  - A 43-year-old man known case of retropositive illness presented with abdomen pain
      of 15 days and loose stools for 10 days. Loose stools were foul smelling and
      blood stained. The patient was a known case of type 2 diabetes and retroviral
      illness on highly active antiretroviral therapy (HAART). General physical
      examination was normal. On examination an irregular mass was palpable in the
      right iliac fossa and right flank. The mass was hard in nature; irregular with
      restricted mobility. There was no palpable liver or spleen. CT of the abdomen and
      pelvis revealed a well-defined heterogeneously enhancing hypodense mass lesion
      measuring 16 * 11.7 * 12 cm involving the ileocaecal region and extending
      medially and inferiorly to sigmoid colon and rectum. A colonoscopy showed a
      proliferative highly vascular mass 15 cm from anal verge at the rectosigmoid
      junction. Histopathology revealed sheets of neoplastic lymphoid cells in rectal
      wall suggestive of non-Hodgkins lymphoma.

PMID- 24014337
TI  - Fahr's disease: bilateral symmetrical striopallidodentate calcification in two
      brothers with two distinct presentations.
AB  - Bilateral striopallidodentate calcinosis, commonly known as Fahr's disease is a
      rare clinical entity present mainly with extrapyramidal signs and accompanied
      with metabolic, biochemical, neuroradiological and neuropsychiatric situations.
      It is characterised by the symmetrical and bilateral intracranial deposition of
      calcium associated with cell loss in the basal ganglia, cerebral cortex and
      cerebellum.In this study, we discussed two brothers' cases of Fahr's diseases who
      presented with different symptomatology. The first presented with walking
      difficulty, cramps and dysarthria and moderate memory impairment whereas the
      second with vertigo, ataxia, forgetfulness and headache. CT scans of both
      patients revealed intracranial diffuse bilateral calcifications in the basal
      ganglia and the cerebellum. The second patient revealed progressive cerebral
      atrophy but reduction in the calcification. Fahr's disease, although encountered
      rarely, should also be taken into account in the differential diagnosis of cases
      with abnormal intracranial calcifications along with other familial, congenital
      and metabolic diseases and syndromes.

PMID- 24014338
TI  - Multiple and superimposed Mongolian spots.

PMID- 24014339
TI  - "Hardly worth the effort"? Medical journals' policies and their editors' and
      publishers' views on trial registration and publication bias: quantitative and
      qualitative study.
AB  - OBJECTIVES: To determine the proportion of medical journals requiring trial
      registration and to understand their reasons for adopting (or not adopting) such
      policies and other measures designed to reduce publication bias. DESIGN:
      Quantitative study of journals' instructions to authors (in June 2012) and
      qualitative study of editors' and publishers' views on trial registration and
      publication bias (carried out in Autumn 2012). SETTING: Random selection of 200
      medical journals publishing clinical trials identified from the Cochrane CENTRAL
      database. PARTICIPANTS: Editors (n=13) and publishers (n=3) of journals with
      different policies on trial registration (and with recently changed policies)
      identified from the survey of their instructions to authors. RESULTS: Only 55/200
      journals (28%) required trial registration according to their instructions and a
      further three (2%) encouraged it. The editors and publishers interviewed
      explained their journals' reluctance to require registration in terms of not
      wanting to lose out to rival journals, not wanting to reject otherwise sound
      articles or submissions from developing countries, and perceptions that such
      policies were not relevant to all journals. Some interviewees considered that
      registration was unnecessary for small or exploratory studies. CONCLUSIONS:
      Although many major medical journals state that they will only publish clinical
      trials that have been prospectively registered, and such policies have been
      associated with a dramatic increase in the number of trials being registered,
      most smaller journals have not adopted such policies. Editors and publishers may
      be reluctant to require registration because they do not understand its benefits
      or because they fear that adopting such a policy would put their journal at a
      disadvantage to competitors.

PMID- 24014340
TI  - Doctor bashing and the brain drain.

PMID- 24014341
TI  - Treatment for sexual offenders against children.

PMID- 24014342
TI  - Healing with an eye on the clock.

PMID- 24014343
TI  - New oral hypoglycaemics fail to show cardiovascular benefits.

PMID- 24014344
TI  - Prosecutors defend decision not pursue doctors over sex selection abortions.

PMID- 24014345
TI  - Changes of the donor nerve in end-to-side neurorrhaphies with epineurial window
      and partial neurectomy: a long-term evaluation in the rat model.
AB  - End-to-side (ETS) neurorrhaphy has been applied in the repair of peripheral nerve
      injuries and in babysitter procedures. However, the long-term changes of donor
      nerve and muscle after ETS remain unknown. This study was designed to investigate
      long-term changes in donor nerve and muscle in a rat model. Sixty Lewis rats were
      equally allocated into three groups of 20 rats. The peroneal nerve was divided.
      In Group A, end-to-end (ETE) neurorrhaphy was performed. In Group B, ETS was
      performed to an epineurial window on the tibial nerve. In Group C, ETS was
      performed to the tibial nerve with 40% partial neurectomy. The following data
      were obtained at 6, 12, 18, and 24 weeks postoperatively: latency delaying rate
      (LDR), amplitude recovery rate (ARR), myelinated fiber counts, muscle force and
      weight, and cross-sectional area of gastrocnemius muscle fibers. The results
      showed no significant changes of the donor nerve and muscle in Group B. Nerve
      regeneration was found in the peroneal nerve, and myelinated fiber number was
      significantly decreased when compared to the nerve with ETE. In Group C, the
      myelinated axon number in the peroneal nerve was equivalent to the level in ETE
      repair. However, function and structure of the donor nerve and muscle were
      significantly impaired in the early postoperative period. Nonetheless, full
      recovery was observed 24 weeks after surgery. Both ETS with epineurial window and
      40% donor nerve neurectomy showed reinnervation of the recipient nerve without
      structural and functional changes of the donor system in a long-term follow-up.
      Partial neurectomy may promote recipient nerve regeneration, but at the cost of
      donor neuromuscular compromises in the early postoperative period. This study
      provides long-term evidence for further investigation of ETS in peripheral nerve
      repair and in babysitter procedures.

PMID- 24014347
TI  - An overview and online registry of microvillus inclusion disease patients and
      their MYO5B mutations.
AB  - Microvillus inclusion disease (MVID) is one of the most severe congenital
      intestinal disorders and is characterized by neonatal secretory diarrhea and the
      inability to absorb nutrients from the intestinal lumen. MVID is associated with
      patient-, family-, and ancestry-unique mutations in the MYO5B gene, encoding the
      actin-based motor protein myosin Vb. Here, we review the MYO5B gene and all
      currently known MYO5B mutations and for the first time methodologically
      categorize these with regard to functional protein domains and recurrence in
      MYO7A associated with Usher syndrome and other myosins. We also review animal
      models for MVID and the latest data on functional studies related to the myosin
      Vb protein. To congregate existing and future information on MVID geno
      /phenotypes and facilitate its quick and easy sharing among clinicians and
      researchers, we have constructed an online MOLGENIS-based international patient
      registry (www.MVID-central.org). This easily accessible database currently
      contains detailed information of 137 MVID patients together with reported
      clinical/phenotypic details and 41 unique MYO5B mutations, of which several
      unpublished. The future expansion and prospective nature of this registry is
      expected to improve disease diagnosis, prognosis, and genetic counseling. 

PMID- 24014346
TI  - Characterisation of CMP-sialic acid transporter substrate recognition.
AB  - CMP-sialic acid transporter: We report an in-depth, multidisciplinary, structural
      study that has identified the amino acid residues intimately involved in CMP
      sialic acid transporter (CST) substrate specificity. Our data provide a
      significant contribution towards a better understanding the structure-function
      relationship of this important family of transporters and the rational design of
      CST inhibitors. 

PMID- 24014348
TI  - A biopsychosocial model of body image concerns and disordered eating in early
      adolescent girls.
AB  - Body image and eating concerns are prevalent among early adolescent girls, and
      associated with biological, psychological and sociocultural risk factors. To
      date, explorations of biopsychosocial models of body image concerns and
      disordered eating in early adolescent girls are lacking. A sample of 488 early
      adolescent girls, mean age = 12.35 years (SD = 0.53), completed a questionnaire
      assessing depressive symptoms, self-esteem, body mass index (BMI), sociocultural
      appearance pressures, thin-ideal internalization, appearance comparison, body
      image concerns and disordered eating. Structural equation modelling was conducted
      to test a hypothetical model in which internalization and comparison were
      mediators of the effect of both negative affect and sociocultural influences on
      body image concerns and disordered eating. In addition, the model proposed that
      BMI would impact body image concerns. Although the initial model was a poor fit
      to the data, the fit was improved after the addition of a direct pathway between
      negative affect and bulimic symptoms. The final model explained a large to
      moderate proportion of the variance in body image and eating concerns. This study
      supports the role of negative affect in biopsychosocial models of the development
      of body image concerns and disordered eating in early adolescent girls.
      Interventions including strategies to address negative affect as well as
      sociocultural appearance pressures may help decrease the risk for body image
      concerns and disordered eating among this age group.

PMID- 24014350
TI  - Female moth pheromones.
AB  - The sex pheromone, a volatile secreted by a female moth, is stored in the
      pheromone gland and can be easily extracted with hexane. The extract is
      effectively analyzed using a gas chromatography combined with an electro
      antennogram detector (GC-EAD) and a mass spectrometry (GC-MS), both of which are
      equipped with a capillary column. GC-EAD analysis indicates the number of
      pheromone components that have a different chromatographic behavior. The mass
      spectrum measured by GC-MS suggests the outline of the chemical structure. In
      addition to a comparison with chemical data of authentic synthetic compounds,
      micro-chemical reactions reveal a precise structure of the natural pheromone.
      Finally, the chemical structure is confirmed by field evaluation of the synthetic
      pheromone. 

PMID- 24014349
TI  - The effects of media violence on anxiety in late adolescence.
AB  - Exposure to media violence is related to anxiety in youth, but the causality of
      the effect has not been established. This experimental study examined the effects
      of media violence on anxiety, blood pressure, and heart rate in late adolescents.
      We also examined whether these responses varied by previous exposure to media and
      real-life violence. College students (N = 209; M age = 18.74; 75 % female; 50 %
      Caucasian, 34 % African American, 9 % Asian, 3 % Hispanic, and 3 % other racial
      minorities) were randomized to view either violent or nonviolent high-action
      movie clips. Participants reported on their anxiety before and after watching the
      clips, as well as their previous exposure to violence. Measures of blood pressure
      and heart rate were taken at baseline and during movie viewing. Participants
      watching violent movie clips showed a greater anxiety increase than those
      watching nonviolent clips. Both groups experienced increased blood pressure and
      reduced heart rate during movie watching compared to baseline. Prior exposure to
      media violence was associated with diminished heart rate response. Additionally,
      students previously exposed to high levels of real-life violence showed lower
      blood pressure increases when watching violent clips compared to nonviolent
      clips. Thus, relatively brief exposure to violent movie clips increased anxiety
      among late adolescents. Prior exposure to media and real-life violence were
      associated with lower physiological reactivity to high-action and violent movies,
      respectively, possibly indicating desensitization. Future studies should
      investigate long-term anxiety and physiological consequences of regular exposure
      to media violence in adolescence. 

PMID- 24014351
TI  - Pheromones in the fruit fly.
AB  - The identification of pheromones (chemical communication cues) is critical to our
      understanding of complex social behavior in insects and other animals. In this
      chapter, we describe analytical methods for the purification of lipid pheromones
      by thin layer chromatography and the quantification and determination of their
      elemental composition by mass spectrometry. 

PMID- 24014353
TI  - Murine nonvolatile pheromones: isolation of exocrine-gland secreting Peptide 1.
AB  - Our search for a substance recognized by the vomeronasal neurons revealed that
      the extra-orbital lacrimal gland (ELG) isolated from adult male mice produced the
      male-specific peptide pheromone exocrine gland-secreting peptide 1 (ESP1). The
      following protocol reveals how ESP1 may be extracted from the ELG, purified using
      anion-exchange and reverse-phase high-performance liquid chromatography (HPLC),
      and analyzed by mass spectrometry. This protocol has been specifically designed
      for the purification of ESP1, but may be modified to isolate a variety of
      peptides from the exocrine glands. Peptides purified in this manner may help
      further define the molecular mechanisms underlying pheromone communication in the
      vomeronasal system. 

PMID- 24014352
TI  - Analysis of volatile mouse pheromones by gas chromatography mass spectrometry.
AB  - High-precision quantitative profiling of volatile organic constituents in rodent
      physiological fluids and glandular secretions is needed to relate olfactory
      signals to physiology and behavior. Whereas capillary gas chromatography-mass
      spectrometry (GC-MS) analysis has become the most widely applied in such
      investigations, the extraction and preconcentration of volatile organics is
      arguably the most critical step in the overall analytical task. In this chapter,
      we describe technical details of two main sample extraction procedures used in
      our laboratory: dynamic headspace trapping, and stir bar sorptive extraction
      (SBSE). They have been demonstrated here for the chromatographic analysis of
      mouse urine, serum, saliva, and preputial gland specimens. 

PMID- 24014354
TI  - Chemical analysis of aquatic pheromones in fish.
AB  - Pheromones are chemicals that pass between members of the same species that have
      inherent meaning. In the case of fish, pheromones are water-soluble and found in
      low concentrations. As such, sensitive and selective methods are needed to
      separate and analyze these pheromones from an environmental matrix that may
      contain many other chemicals. This chapter describes a generic method used to
      concentrate and identify these chemicals and two extremely sensitive and
      selective methods for analysis, namely, mass spectrometry and enzyme-linked
      immunosorbent assay. 

PMID- 24014356
TI  - Identification of chemosensory receptor genes from vertebrate genomes.
AB  - Chemical senses are essential for the survival of animals. In vertebrates, mainly
      three different types of receptors, olfactory receptors (ORs), vomeronasal
      receptors type 1 (V1Rs), and vomeronasal receptors type 2 (V2Rs), are responsible
      for the detection of chemicals in the environment. Mouse or rat genomes contain
      >1,000 OR genes, forming the largest multigene family in vertebrates, and have
      >100 V1R and V2R genes as well. Recent advancement in genome sequencing enabled
      us to computationally identify nearly complete repertories of OR, V1R, and V2R
      genes from various organisms, revealing that the numbers of these genes are
      highly variable among different organisms depending on each species' living
      environment. Here I would explain bioinformatic methods to identify the entire
      repertoires of OR, V1R, and V2R genes from vertebrate genome sequences. 

PMID- 24014355
TI  - Analysis of ascarosides from Caenorhabditis elegans using mass spectrometry and
      NMR spectroscopy.
AB  - The nematode Caenorhabditis elegans secretes a family of water-soluble small
      molecules, known as the ascarosides, into its environment and uses these
      ascarosides in chemical communication. The ascarosides are derivatives of the 3,6
      dideoxysugar ascarylose, modified with different fatty acid-derived side chains.
      C. elegans uses specific ascarosides, which are together known as the dauer
      pheromone, to trigger entry into the stress-resistant dauer larval stage. In
      addition, C. elegans uses specific ascarosides to control certain behaviors,
      including mating attraction, aggregation, and avoidance. Although in general the
      concentration of the ascarosides in the environment increases with population
      density, C. elegans can vary the types and amounts of ascarosides that it
      secretes depending on the culture conditions under which it has been grown and
      its developmental history. Here, we describe how to grow high-density worm
      cultures and the bacterial food for those cultures, as well as how to extract the
      culture medium to generate a crude pheromone extract. Then, we discuss how to
      analyze the types and amounts of ascarosides in that extract using mass
      spectrometry and NMR spectroscopy. 

PMID- 24014357
TI  - Functional assays for insect olfactory receptors in Xenopus oocytes.
AB  - Reconstitution of olfactory or pheromone receptors in heterologous expression
      systems greatly facilitates the functional analysis of these receptors. Xenopus
      laevis oocytes can be used to efficiently express insect olfactory or pheromone
      receptors. In this chapter, we describe how to use Xenopus laevis oocytes for
      functional assays of insect olfactory receptors. The procedure can be subdivided
      into the four following steps: (1) in vitro complementary RNA (cRNA) synthesis,
      (2) isolation of oocytes from female Xenopus laevis, (3) cRNA microinjection into
      oocytes, and (4) two-electrode voltage-clamp recording. This system can be used
      to identify odor or pheromone ligands and to analyze structure-function
      relationships involving receptor proteins of interest. 

PMID- 24014358
TI  - A protocol for heterologous expression and functional assay for mouse pheromone
      receptors.
AB  - Innate social behaviors like intermale aggression, fear, and mating rituals are
      important for survival and propagation of a species. In mice, these behaviors
      have been implicated to be mediated by peptide pheromones that are sensed by a
      class of G protein-coupled receptors, vomeronasal receptor type 2 (V2Rs),
      expressed in the pheromone-detecting vomeronasal organ (VNO) (Chamero et al.,
      Nature 450:899-902, 2007; Haga et al., Nature 466:118-122, 2010; Kimoto et al.,
      Curr Biol 17:1879-1884, 2007; Leinders-Zufall et al., Nat Neurosci 12:1551-1558,
      2009; Papes et al., Cell 141:692-703, 2010). Matching V2Rs with their cognate
      ligands is required to understand what receptors the biologically relevant
      pheromones are acting on. However, this goal has been greatly limited by the
      unavailability of appropriate heterologous tools commonly used to carry out
      receptor deorphanization, due to the fact that this family of receptors fails to
      traffic to the surface of heterologous cells. We have demonstrated that
      calreticulin, a housekeeping chaperone commonly expressed in most eukaryotic
      cells, is sparsely expressed in the vomeronasal sensory neurons (VSNs). Stable
      knock down of calreticulin in a HEK293T derived cell line (R24 cells) allows us
      to functionally express V2Rs on the surface of heterologous cells. In this
      chapter we describe protocols for maintenance and expansion of the R24 cell line
      and functional assays for V2Rs using these cells. 

PMID- 24014359
TI  - Genetic manipulation to analyze pheromone responses: knockouts of multiple
      receptor genes.
AB  - Gene targeting in the mouse is an essential technique to study gene function in
      vivo. Multigene families encoding vomeronasal receptor (VR) type 1 and type 2
      consist of ~300 intact genes, which are clustered at multiple loci in the mouse
      genome. To understand the function of VRs and neurons expressing a particular VR
      in vivo, individual endogenous receptor genes can be manipulated by conventional
      gene targeting to create loss-of-function mutations or to visualize neurons and
      their axons expressing the VR. Multiple receptor genes in a cluster can also be
      deleted simultaneously by chromosome engineering, allowing analysis of function
      of a particular VR subfamily. Here, we describe protocols for conventional gene
      targeting and chromosome engineering for deleting a large genomic region in mouse
      embryonic stem (ES) cells. 

PMID- 24014360
TI  - Electroantennogram and single sensillum recording in insect antennae.
AB  - Electrophysiology is an invaluable technique to quickly and quantitatively assess
      the response of the olfactory system to odor stimuli. For measuring the response
      of the insect antenna, two basic techniques exist, electroantennography and
      single sensillum recording. Here, we describe the general practice of both
      methods in terms of equipment used, insect preparation, recording technique, and
      basic analysis. 

PMID- 24014361
TI  - Calcium imaging of pheromone responses in the insect antennal lobe.
AB  - Calcium imaging is a powerful technique that permits the visual monitoring of
      neural responses to pheromones and other odors in large ensembles of neurons.
      Here, we describe a method that permits the monitoring of Drosophila antennal
      lobe responses to odors using the genetically encoded calcium monitor GCaMP. 

PMID- 24014362
TI  - Live cell calcium imaging of dissociated vomeronasal neurons.
AB  - Sensory neurons in the vomeronasal organ (VNO) are thought to mediate a
      specialized olfactory response. Currently, very little is known about the
      identity of stimulating ligands or their cognate receptors that initiate neural
      activation. Each sensory neuron is thought to express 1 of approximately 250
      variants of Vmn1Rs, Vmn2Rs (A, B, or D), or FPRs which enables it to be tuned to
      a subset of ligands (Touhara and Vosshall, Annu Rev Physiol 71:307-332, 2009).
      The logic of how different sources of native odors or purified ligands are
      detected by this complex sensory repertoire remains mostly unknown. Here, we
      describe a method to compare and analyze the response of VNO sensory neurons to
      multiple stimuli using conventional calcium imaging. This method differs from
      other olfactory imaging approaches in that we dissociate the tightly packed
      sensory epithelium into individual single cells. The advantages of this approach
      include (1) the use of a relatively simple approach and inexpensive microscopy,
      (2) comparative analysis of several hundreds of neurons to multiple stimuli with
      single-cell resolution, and (3) the possibility of isolating single cells of
      interest to further analyze by molecular biology techniques including in situ RNA
      hybridization, immunofluorescence, or creating single-cell cDNA libraries (Malnic
      et al., Cell 96:713-723, 1999). 

PMID- 24014363
TI  - Whole-mount imaging of responses in mouse vomeronasal neurons.
AB  - Imaging permits the visualization of neural activity from the whole-mount
      vomeronasal sensory epithelium with single-cell resolution. The preparation
      preserves an intact tissue environment, enabling the robust detection of cellular
      responses upon chemical stimulation and study of the precise 3D mapping of
      vomeronasal sensory neuron (VSN) functional types within the epithelium. Using
      objective-coupled planar illumination (OCPI) microscopy to perform fast
      volumetric imaging, we routinely record the responses of thousands of VSNs for
      hours from a single intact vomeronasal organ preparation. Here we document the
      preparation of the whole-mounted vomeronasal epithelium, multichannel stimulus
      delivery, and three-dimensional calcium imaging by OCPI microscopy. 

PMID- 24014364
TI  - Calcium imaging of vomeronasal organ response using slice preparations from
      transgenic mice expressing G-CaMP2.
AB  - The vomeronasal organ (VNO) in vertebrate animals detects pheromones and
      interspecies chemical signals. We describe in this chapter a Ca(2+) imaging
      approach using transgenic mice that express the genetically encoded Ca(2+) sensor
      G-CaMP2 in VNO tissue. This approach allows us to analyze the complex patterns of
      the vomeronasal neuron response to large number of chemosensory stimuli. 

PMID- 24014365
TI  - The electrovomeronasogram: field potential recordings in the mouse vomeronasal
      organ.
AB  - Mammalian vomeronasal neurons (VSNs) located in the sensory epithelium of the
      vomeronasal organ (VNO) detect and transduce molecular cues emitted by other
      individuals and send this information to the olfactory forebrain. The initial
      steps in the detection of pheromones and other chemosignals by VSNs involve
      interaction of a ligand with a G protein-coupled receptor and downstream
      activation of the primary signal transduction cascade, which includes activation
      of ion channels located in microvilli and the dendritic tip of a VSN. The
      electrovomeronasogram (EVG) recording technique provides a sensitive means
      through which ligand-induced activation of populations of VSNs can be recorded
      from the epithelial surface using an intact, ex vivo preparation of the mouse
      VNO. We describe methodological aspects of this preparation and the EVG recording
      technique which, together with single-cell recordings, contributed significantly
      to our understanding of mammalian vomeronasal function, the identification of
      pheromonal ligands, and the analysis of mice with targeted deletions in specific
      signal transduction molecules such as Trpc2, Galphao, V1R, or V2R receptors. 

PMID- 24014366
TI  - Electrical recordings from the accessory olfactory bulb in VNO-AOB ex vivo
      preparations.
AB  - Electrical recordings from individual accessory olfactory bulb neurons allow
      exploration of the functional properties of this important pheromonal processing
      circuit. Several approaches to performing such recordings have been used. Here,
      we describe ex vivo methods that we have found useful for recording from
      accessory olfactory bulb neurons using simple extracellular glass electrodes. 

PMID- 24014367
TI  - Pheromone-induced expression of immediate early genes in the mouse vomeronasal
      sensory system.
AB  - Immediate early genes (IEGs) are powerful tools for visualizing activated neurons
      and extended circuits that are stimulated by sensory input. Several kinds of IEGs
      (e.g., c-fos, egr-1) have been utilized for detecting activated receptor neurons
      in the pheromone sensory organ called the vomeronasal organ (VNO), as well as for
      mapping the neurons within the central nervous system (CNS) excited by
      pheromones.In this chapter, we describe the procedure for the detection of
      pheromone-induced neural activation in the VNO and CNS using the c-Fos
      immunostaining technique. 

PMID- 24014368
TI  - Insect pheromone behavior: fruit fly.
AB  - The amenability to genetics of Drosophila melanogaster has made this organism one
      of the best-suited models for studying the neurobiology of pheromone-guided
      behavior. Single-male assays use the minigene encoding the thermosensitive
      channel dTrpA1 to activate neurons expressing fruitless (fru), a major courtship
      regulator gene, and thereby induce most of the elementary courtship acts in a
      solitary male exposed to temperature increase. Tethered male assays allow Ca(2+)
      imaging of neuronal activities of a male fly displaying courtship behavior on a
      treadmill when stimulated with a female or pheromones. Here we describe technical
      details of these assays. 

PMID- 24014369
TI  - Quantitative assessment of pheromone-induced Dauer formation in Caenorhabditis
      elegans.
AB  - Environmental conditions experienced during early larval stages dictate the
      developmental trajectory of the nematode C. elegans. Favorable conditions such as
      low population density, abundant food, and lower temperatures allow reproductive
      growth, while stressful conditions promote entry of second-stage (L2) larvae into
      the alternate dauer developmental stage. Population density is signaled by the
      concentration and composition of a complex mixture of small molecules that is
      produced by all stages of animals, and is collectively referred to as dauer
      pheromone; pheromone concentration is a major trigger for dauer formation. Here,
      we describe a quantitative dauer formation assay that provides a measure of the
      potency of single or mixtures of pheromone components in regulating this critical
      developmental decision. 

PMID- 24014370
TI  - Acute behavioral responses to pheromones in C. elegans (adult behaviors:
      attraction, repulsion).
AB  - The pheromone drop test is a simple and robust behavioral assay to quantify acute
      avoidance of pheromones in C. elegans, and the suppression of avoidance by
      attractive pheromones. In the pheromone drop test, water-soluble C. elegans
      pheromones are individually applied to animals that are freely moving on a large
      plate. Upon encountering a repellent, each C. elegans animal may or may not try
      to escape by making a long reversal. The fraction of animals that make a long
      reversal response indicates the repulsiveness of a given pheromone to a specific
      genotype/strain of C. elegans. Performing the drop test in the presence of
      bacterial food enhances the avoidance response to pheromones. Attraction to
      pheromones can be assayed by the suppression of reversals to repulsive pheromones
      or by the suppression of the basal reversal rate to buffer. 

PMID- 24014371
TI  - Behavioral analysis of pheromones in fish.
AB  - Pheromones are chemicals that pass between members of the same species which have
      inherent meaning. Because most fish pheromones are mixtures, and their actions
      can be complex, behavioral assays are required to identify them. This chapter
      describes a few strategies and two specific methods (one for measuring attraction
      and another for sexual arousal) that can serve this purpose in fishes that live
      in nonflowing water such as the carps. 

PMID- 24014372
TI  - Analysis of male aggressive and sexual behavior in mice.
AB  - Pheromone and odor signals play a pivotal role in male mouse reproductive
      behaviors, such as sexual and aggressive behavior. There are several methods used
      to assess male behaviors, each of which examines a unique aspect of the
      biological function of mice. There are two major ways of assessing male
      aggressive behavior in mice, one is using isolation-induced aggression, and the
      other is territorial aggression in pair-housed males. To analyze male sexual
      behavior, a female mouse that is hormone-primed with estradiol and progesterone
      is usually introduced into a male home range, and mounting, intromission, and
      ejaculation behaviors are observed for 1 h. Here, we summarize the detailed
      protocols for assessing male behaviors. 

PMID- 24014373
TI  - Assessment of urinary pheromone discrimination, partner preference, and mating
      behaviors in female mice.
AB  - Behavioral testing methods are described for determining whether female mice can
      discriminate between volatile urinary pheromones of conspecifics of the same vs.
      opposite sex and/or in different endocrine conditions, for determining sexual
      partner preference, for quantifying receptive (lordosis) behavior, and for
      monitoring the expression of male-typical mounting behavior in female mice. 

PMID- 24014374
TI  - Assessing postpartum maternal care, alloparental behavior, and infanticide in
      mice: with notes on chemosensory influences.
AB  - Chemosensory signaling influences maternal care and other innate behaviors toward
      conspecific young animals in rodents. In this chapter, we describe basic
      protocols for assessment of postpartum maternal behavior and other pup-directed
      behaviors in laboratory mice. The specific aim of this protocol is to screen out
      the abnormal phenotypes in parenting of genetic mutant mice under the standard
      housing condition. The possible underlying mechanisms for a given abnormality in
      the mother-young interaction are briefly suggested as well. 

PMID- 24014375
TI  - Testing smell when it is really vital: behavioral assays of social odors in the
      neonatal mouse.
AB  - The initial interactions of mouse newborns with their mother are crucial for
      their survival. These interactions rapidly end in the pups reaching nipples and
      getting milk. While we realize that olfaction is clearly prevailing in the
      success of these first suckling episodes, we still understand little about the
      nature and range of the natural odorants involved. Here we non-exhaustively
      describe some experimental principles and methods to assay the behavior of newly
      born and infant mice exposed to different odor stimuli from conspecifics. Testing
      neonatal and young mice with chemostimuli which they are evolutionarily or
      developmentally canalized to detect may be a productive way to trace
      unanticipated odor signals. Moreover, testing neonates also may also lead to
      characterize unsuspected strategies of murine females to produce and release odor
      messages. 

PMID- 24014376
TI  - An assay for human chemosignals.
AB  - Like all mammals, humans use chemosignals. Nevertheless, only few such
      chemosignals have been identified. Here we describe an experimental arrangement
      that casts a wide net for the possible chemosignaling functions of target
      molecules. This experimental arrangement can be used in concert with various
      methods for measuring the human behavioral and brain responses, including
      psychophysiology and brain imaging. Moreover, many of the methodological issues
      we describe are relevant to any study with human chemosignals. 

PMID- 24014377
TI  - Equol as a potent radiosensitizer in estrogen receptor-positive and -negative
      human breast cancer cell lines.
AB  - BACKGROUND: Breast cancer is the most common cause of cancer death among women
      worldwide, and diet plays an important role in its prevention and progression.
      Radiotherapy has a limited but important role in the management of nearly every
      stage of breast cancer. We studied whether equol, the major metabolite of the
      soybean isoflavone daidzein, could enhance radiosensitivity in two human breast
      cancer cell lines (T47D and MDA-MB-231). METHODS: MTT assay was used to examine
      equol's effect on cell viability. Sensitivity of cells to equol, radiation and a
      combination of both was determined by colonogenic assays. Induction of apoptosis
      by equol, radiation and the combination of both was also determined by acridine
      orange/ethidium bromide double staining fluorescence microscopy. DNA strand
      breaks were assessed by Comet assay. RESULT: MTT assay showed that equol (0.1-350
      MUM) inhibited MDA-MB-231 and T47D cell growth in a time- and dose-dependent
      manner. Treatment of cells with equol for 72 h (MDA-MB-231) and 24 h (T47D) was
      found to inhibit cell growth with IC50 values of 252 MUM and 228 MUM,
      respectively. Furthermore, pretreatment of cells with 50 MUM equol for 72 h (MDA
      MB-231) and 24 h (T47D) sensitized the cells to irradiation. Equol was also found
      to enhance radiation-induced apoptosis. Comet assay results showed that the
      radiosensitizing effect of equol was accompanied by increased radiation-induced
      DNA damages. CONCLUSIONS: These results suggest for the first time that equol can
      be considered as a radiosensitizing agent and its effects may be due to
      increasing cell death following irradiation, increasing the remaining radiation
      induced DNA damage and thus reducing the surviving fraction of irradiated cells.

PMID- 24014379
TI  - Counseling for prenatal diagnosis and termination of pregnancy due to thalassemia
      major: a survey of health care workers' practices in Malaysia.
AB  - OBJECTIVE: Genetic counseling for thalassemia carriers is conducted by
      nongeneticist health care workers (HCWs) in many countries. The aim of the study
      was to assess Malaysian HCWs' genetic counseling practices with regards to
      discussing prenatal diagnosis (PND) and termination of pregnancy (TOP) when
      counseling thalassemia carriers. METHOD: A total of 118 Malaysian HCWs (52
      doctors and 66 nurses) completed a structured questionnaire that enquired if they
      would discuss PND and TOP when counseling couples with thalassemia traits, and
      reasons for their responses were explored. RESULTS: All the nurses and 50 (96.1%)
      doctors were in favor of discussing PND. Only 29 (58%) doctors and 33 (50%)
      nurses were agreeable to discuss about the option of TOP. Main reasons given for
      declining to discuss TOP were views that "the condition was not serious enough"
      (54.9%), TOP is not permissible by their religion (17.6%) and abortion for this
      indication was illegal (13.7%). CONCLUSION: The results showed that HCWs in
      Malaysia lacked the comprehensive information and necessary skills required when
      counseling thalassemia carriers. When nongeneticist HCWs are tasked with such
      responsibilities, their practices and attitudes should be regularly evaluated so
      that areas of deficiencies could be identified and addressed.

PMID- 24014380
TI  - Treatment of recurrent lingual nerve end-neuroma: A case report.
AB  - A neuroma is a collection of disorganized nerve sprouts emanating from an
      interruption of axonal continuity, forming within a collagen scar as the nerve
      attempts to regenerate. Lingual neuroma formation secondary to iatrogenic trauma
      to the tongue is likely not uncommon; however, we could not find a report in the
      literature of treatment of a distal tongue end-neuroma treated by resection and
      implantation into muscle. Here we describe a patient who experienced debilitating
      chronic tongue pain after excision of a benign mass. After failing conservative
      management, the patient was taken to the operating room where an end-neuroma of
      the lingual nerve was identified and successfully treated by excision and burying
      of the free proximal stump in the mylohyoid muscle. At 17 months postoperatively,
      she remains pain free without dysesthesias.

PMID- 24014378
TI  - VBP15, a novel anti-inflammatory and membrane-stabilizer, improves muscular
      dystrophy without side effects.
AB  - Absence of dystrophin makes skeletal muscle more susceptible to injury, resulting
      in breaches of the plasma membrane and chronic inflammation in Duchenne muscular
      dystrophy (DMD). Current management by glucocorticoids has unclear molecular
      benefits and harsh side effects. It is uncertain whether therapies that avoid
      hormonal stunting of growth and development, and/or immunosuppression, would be
      more or less beneficial. Here, we discover an oral drug with mechanisms that
      provide efficacy through anti-inflammatory signaling and membrane-stabilizing
      pathways, independent of hormonal or immunosuppressive effects. We find VBP15
      protects and promotes efficient repair of skeletal muscle cells upon laser
      injury, in opposition to prednisolone. Potent inhibition of NF-kappaB is mediated
      through protein interactions of the glucocorticoid receptor, however VBP15 shows
      significantly reduced hormonal receptor transcriptional activity. The translation
      of these drug mechanisms into DMD model mice improves muscle strength, live
      imaging and pathology through both preventive and post-onset intervention
      regimens. These data demonstrate successful improvement of dystrophy independent
      of hormonal, growth, or immunosuppressive effects, indicating VBP15 merits
      clinical investigation for DMD and would benefit other chronic inflammatory
      diseases. 

PMID- 24014381
TI  - Phase II study of cilengitide in the treatment of refractory or relapsed high
      grade gliomas in children: a report from the Children's Oncology Group.
AB  - BACKGROUND: Cilengitide, an alphav integrin antagonist, has demonstrated activity
      in recurrent adult glioblastoma (GBM). The Children's Oncology Group ACNS0621
      study thus evaluated whether cilengitide is active as a single agent in the
      treatment of children with refractory high-grade glioma (HGG). Secondary
      objectives were to investigate the pharmacokinetics and pharmacogenomics of
      cilengitide in this population. METHODS: Cilengitide (1800 mg/m(2)/dose
      intravenous) was administered twice weekly until evidence of disease progression
      or unacceptable toxicity. Thirty patients (age range, 1.1-20.3 years) were
      enrolled, of whom 24 were evaluable for the primary response end point. RESULTS:
      Toxicity was infrequent and mild, with the exception of one episode of grade 2
      pain possibly related to cilengitide. Two intratumoral hemorrhages were reported,
      but only one (grade 2) was deemed to be possibly related to cilengitide and was
      in the context of disease progression. One patient with GBM received cilengitide
      for 20 months and remains alive with continuous stable disease. There were no
      other responders, with median time to tumor progression of 28 days (range, 11-114
      days). Twenty-one of the 24 evaluable patients died, with a median time from
      enrollment to death of 172 days (range, 28-325 days). The 3 patients alive at the
      time of this report had a follow-up time of 37, 223, and 1068 days, respectively.
      CONCLUSIONS: We conclude that cilengitide is not effective as a single agent for
      refractory pediatric HGG. However, further study evaluating combination therapy
      with cilengitide is warranted before a role for cilengitide in the treatment of
      pediatric HGG can be excluded.

PMID- 24014383
TI  - Do we need clinical registries?

PMID- 24014382
TI  - Toll-like receptor 2 mediates microglia/brain macrophage MT1-MMP expression and
      glioma expansion.
AB  - BACKGROUND: Glioblastomas are the most aggressive primary brain tumors in humans.
      Microglia/brain macrophage accumulation in and around the tumor correlates with
      malignancy and poor clinical prognosis of these tumors. We have previously shown
      that microglia promote glioma expansion through upregulation of membrane type 1
      matrix metalloprotease (MT1-MMP). This upregulation depends on signaling via the
      Toll-like receptor (TLR) adaptor molecule myeloid differentiation primary
      response gene 88 (MyD88). METHODS: Using in vitro, ex vivo, and in vivo
      techniques, we identified TLR2 as the main TLR controlling microglial MT1-MMP
      expression and promoting microglia-assisted glioma expansion. RESULTS: The
      implantation of mouse GL261 glioma cells into TLR2 knockout mice resulted in
      significantly smaller tumors, reduced MT1-MMP expression, and enhanced survival
      rates compared with wild-type control mice. Tumor expansion studied in
      organotypic brain slices depended on both parenchymal TLR2 expression and the
      presence of microglia. Glioma-derived soluble factors and synthetic TLR2 specific
      ligands induced MT1-MMP expression in microglia from wild-type mice, but no such
      change in MT1-MMP gene expression was observed in microglia from TLR2 knockout
      mice. We also found evidence that TLR1 and TLR6 cofunction with TLR2 as
      heterodimers in regulating MT1-MMP expression in vitro. CONCLUSIONS: Our results
      thus show that activation of TLR2 along with TLRs 1 and/or 6 converts microglia
      into a glioma supportive phenotype.

PMID- 24014384
TI  - Mechanical circulatory support in cardiogenic shock.
AB  - Despite advances in coronary revascularization and widespread use of primary
      percutaneous interventions, cardiogenic shock complicating an acute ST-elevation
      myocardial infarction (CSMI) remains a clinical challenge with high mortality
      rates. Conservative management with catecholamines is associated with serious
      limitations, including arrhythmias, increased myocardial oxygen consumption, and
      inadequate circulatory support. Clinicians have therefore turned to mechanical
      means of circulatory support. Circulatory assist systems for CSMI can be
      distinguished by the method of placement (i.e. percutaneous vs. surgical), the
      type of circulatory support (i.e. left ventricular, right ventricular, or
      biventricular pressure and/or volume unloading), and whether they are combined
      with extracorporal membrane oxygenation (ECMO). The percutaneous assist systems
      most commonly used in CSMI are the intra-aortic balloon pump (IABP), venoarterial
      ECMO, the Impella pump, and the TandemHeart. Decades of clinical studies and
      experience demonstrated haemodynamic improvement, including elevation of
      diastolic perfusion pressure and cardiac output. Recently, the large randomized
      IABP-Shock II Trial did not show a significant reduction in 30-day mortality in
      CSMI with IABP insertion. There are no randomized study data available for ECMO
      use in CSMI. Both the Impella pump and the TandemHeart did not reduce 30-day
      mortality when compared with IABP in small randomized controlled trials (RCTs).
      In conclusion, despite the need for effective mechanical circulatory support in
      CSMI, current devices, as tested, have not been demonstrated to improve short- or
      long-term survival rates. RCTs testing the optimal timing of device therapy and
      optimal device design are needed to improve outcomes in CSMI.

PMID- 24014386
TI  - An unusual cause of intracardiac mass in a heart transplant patient.

PMID- 24014387
TI  - Left ventricular contractile reserve in asymptomatic primary mitral
      regurgitation.
AB  - AIMS: There are very few data regarding the assessment and prognostic value of
      left ventricular contractile reserve (LVCR) in asymptomatic patients with primary
      mitral regurgitation (MR). We aimed to quantify LVCR and to evaluate its
      usefulness for risk stratification in asymptomatic patients with primary MR.
      METHODS AND RESULTS: Comprehensive resting and exercise (EX) transthoracic
      echocardiography, including two-dimensional speckle tracking quantification, were
      performed in 115 consecutive asymptomatic patients with >= moderate degenerative
      MR and no LV dysfunction/dilatation. Left ventricular contractile reserve was
      defined as an EX-induced increase in LV ejection fraction (LVCR(LVEF)) >= 4% or
      in LV global longitudinal strain (LVCR(GLS)) >= 2%. LVCR(LVEF) was present in 54
      patients (47%) and LVCR(GLS) in 58 (50%). The brain natriuretic peptide (BNP)
      level was significantly correlated with EX-induced changes in GLS (r = 0.45, P <
      0.0001), but not in LVEF (r = 0.09, P = 0.31). Patients with no LVCR(GLS) had
      significant lower 3-year cardiac event-free survival (42 +/- 8 vs. 69 +/- 7%, P =
      0.0008). In contrast, there was no significant difference in outcome regarding to
      the presence or absence of LVCR(LVEF) (60 +/- 7 vs. 51 +/- 8%, P = 0.40). The
      multivariable Cox proportional hazard model showed that the absence of LVCR(GLS)
      was a strong independent predictor of cardiac events (HR = 2.27, 95% CI: 1.05
      4.76, P = 0.037), even after adjustment for Ex-echo variables and BNP level. The
      association between LVCR(GLS) and outcome remained significant (HR = 1.6, 95% CI:
      1.1-2.3, P = 0.01) after further adjustment for the resting echocardiographic
      parameters included in the ESC Guidelines. CONCLUSION: In asymptomatic primary
      MR, LVCR seems to be better assessed using EX-induced changes in LV myocardial
      longitudinal function rather than in LVEF. In patients with preserved LV
      function, the absence of LVCR is independently associated with two-fold increase
      in risk of cardiac events. Left ventricular contractile reserve may be useful to
      improve risk stratification and clinical decision-making in these patients.

PMID- 24014385
TI  - Endothelial dysfunction over the course of coronary artery disease.
AB  - The vascular endothelium regulates blood flow in response to physiological needs.
      Endothelial dysfunction is closely related to atherosclerosis and its risk
      factors, and it constitutes an intermediate step on the progression to adverse
      events throughout the natural history of coronary artery disease (CAD), often
      affecting clinical outcomes. Understanding the relation of endothelial function
      with CAD provides an important pathophysiological insight, which can be useful
      both in clinical and research management. In this review, we summarize the
      current knowledge on endothelial dysfunction and its prognostic influence
      throughout the natural history of CAD, from early atherosclerosis to post
      transplant management. 

PMID- 24014388
TI  - Geriatric congenital heart disease: a new challenge in the care of adults with
      congenital heart disease?

PMID- 24014389
TI  - Managing tobacco use: the neglected cardiovascular disease risk factor.
AB  - Cigarette smoking is a major risk factor for cardiovascular disease (CVD) and the
      leading avoidable cause of death worldwide. Exposure to secondhand smoke (SHS)
      increases the risk of CVD among non-smokers. Smoking cessation benefits all
      smokers, regardless of age or amount smoked. The excess risk of CVD is rapidly
      reversible, and stopping smoking after a myocardial infarction reduces an
      individual's risk of CVD mortality by 36% over 2 years. Smoking cessation is a
      key component of primary and secondary CVD prevention strategies, but tobacco use
      often receives less attention from cardiologists than other risk factors, despite
      the availability of proven treatments that improve smoking cessation rates. Both
      psychosocial counselling and pharmacotherapy are effective methods to help
      smokers quit, but they are most effective when used together. The first-line
      medications licensed to aid smoking cessation, nicotine replacement therapy,
      bupropion and varenicline, are effective in and appropriate for patients with
      CVD. An evidence-based approach for physicians is to routinely ask all patients
      about smoking status and SHS exposure, advise all smokers to quit and all
      patients to adopt smoke-free policies for their home and car, and offer all
      smokers in the office or hospital brief counselling, smoking cessation
      pharmacotherapy, and referral to local programmes where psychosocial support can
      be sustained in person or by telephone. Like other chronic diseases, tobacco use
      requires a long-term management strategy. It deserves to be managed as
      intensively as other CVD risk factors. 

PMID- 24014390
TI  - Cardiovascular disease in Europe: epidemiological update.
AB  - This overview provides a Europe-wide update on the current burden of
      cardiovascular disease, and specifically of coronary heart disease and stroke.
      Cardiovascular disease continues to cause a large proportion of deaths and
      disability in Europe, and places a substantial burden on the health care systems
      and economies of Europe. The overall picture, and the distribution of the burden,
      continues to evolve in a developing Europe. There have been major improvements in
      recent years on many measures of cardiovascular disease; however, these
      improvements have not been universal, and substantial inequalities persist. 

PMID- 24014391
TI  - High-density lipoprotein cholesterol, coronary artery disease, and cardiovascular
      mortality.
AB  - AIMS: High-density lipoprotein (HDL) cholesterol is a strong predictor of
      cardiovascular mortality. This work aimed to investigate whether the presence of
      coronary artery disease (CAD) impacts on its predictive value. METHODS AND
      RESULTS: We studied 3141 participants (2191 males, 950 females) of the
      LUdwigshafen RIsk and Cardiovascular health (LURIC) study. They had a mean +/-
      standard deviation age of 62.6 +/- 10.6 years, body mass index of 27.5 +/- 4.1
      kg/m&sup2;, and HDL cholesterol of 38.9 +/- 10.8 mg/dL. The cohort consisted of
      699 people without CAD, 1515 patients with stable CAD, and 927 patients with
      unstable CAD. The participants were prospectively followed for cardiovascular
      mortality over a median (inter-quartile range) period of 9.9 (8.7-10.7) years. A
      total of 590 participants died from cardiovascular diseases. High-density
      lipoprotein cholesterol by tertiles was inversely related to cardiovascular
      mortality in the entire cohort (P = 0.009). There was significant interaction
      between HDL cholesterol and CAD in predicting the outcome (P = 0.007). In
      stratified analyses, HDL cholesterol was strongly associated with cardiovascular
      mortality in people without CAD [3rd vs. 1st tertile: HR (95% CI) = 0.37 (0.18
      0.74), P = 0.005], but not in patients with stable [3rd vs. 1st tertile: HR (95%
      CI) = 0.81 (0.61-1.09), P = 0.159] and unstable [3rd vs. 1st tertile: HR (95% CI)
      = 0.91 (0.59-1.41), P = 0.675] CAD. These results were replicated by analyses in
      3413 participants of the AtheroGene cohort and 5738 participants of the ESTHER
      cohort, and by a meta-analysis comprising all three cohorts. CONCLUSION: The
      inverse relationship of HDL cholesterol with cardiovascular mortality is weakened
      in patients with CAD. The usefulness of considering HDL cholesterol for
      cardiovascular risk stratification seems limited in such patients.

PMID- 24014392
TI  - Does remote ischaemic preconditioning with postconditioning improve clinical
      outcomes of patients undergoing cardiac surgery? Remote Ischaemic Preconditioning
      with Postconditioning Outcome Trial.
AB  - AIMS: The aim of this study was to evaluate whether remote ischaemic
      preconditioning (RIPC) combined with remote ischaemic postconditioning (RIPostC)
      improves the clinical outcomes of patients undergoing cardiac surgery. METHODS
      AND RESULTS: From June 2009 to November 2010, 1280 patients who underwent
      elective cardiac surgery were randomized into the RIPC with RIPostC group or the
      control group in the morning of the surgery. In the RIPC with RIPostC group, four
      cycles of 5-min ischaemia and 5-min reperfusion were administered twice to the
      upper limb-before cardiopulmonary bypass (CPB) or coronary anastomoses for RIPC
      and after CPB or coronary anastomoses for RIPostC. The primary endpoint was the
      composite of major adverse outcomes, including death, myocardial infarction,
      arrhythmia, stroke, coma, renal failure or dysfunction, respiratory failure,
      cardiogenic shock, gastrointestinal complication, and multiorgan failure. Remote
      ischaemic preconditioning with RIPostC did not reduce the composite outcome
      compared with the control group (38.0 vs. 38.1%, respectively; P = 0.998) and
      there was no difference in each major adverse outcome. The intensive care unit
      and hospital stays were not different between the two groups. However, in the off
      pump coronary artery bypass surgery subgroup, multivariate logistic regression
      analysis revealed that RIPC with RIPostC was related to increased composite
      outcome (odds ratio: 1.54; 95% confidence interval: 1.02-2.30; P = 0.038).
      CONCLUSION: Remote ischaemic preconditioning with RIPostC by transient upper limb
      ischaemia did not improve clinical outcome in patients who underwent cardiac
      surgery.

PMID- 24014393
TI  - Towards highly stable storage of sodium ions: a porous Na(3)V(2)(PO(4))(3)/C
      cathode material for sodium-ion batteries.
AB  - A porous Na3 V2 (PO4 )3 cathode material coated uniformly with a layer of
      approximately 6 nm carbon has been synthesized by the sol-gel method combined
      with a freeze-drying process. The special porous morphology and structure
      significantly increases the specific surface area of the material, which greatly
      enlarges the contact area between the electrode and electrolyte, and consequently
      supplies more active sites for sodium ions. When employed as a cathode material
      of sodium-ion batteries, this porous Na3 V2 (PO4 )3 /C exhibits excellent rate
      performance and cycling stability; for instance, it shows quite a flat potential
      plateau at 3.4 V in the potential window of 2.7-4.0 V versus Na(+) /Na and
      delivers an initial capacity as high as 118.9 and 98.0 mA h g(-1) at current
      rates of 0.05 and 0.5 C, respectively, and after 50 cycles, a good capacity
      retention of 92.7 and 93.6 % are maintained. Moreover, even when the discharge
      current density is increased to 5 C (590 mA g(-1) ), an initial capacity of 97.6
      mA h g(-1) can still be achieved, and an exciting capacity retention of 88.6 % is
      obtained after 100 cycles. The good cycle performance, excellent rate capability,
      and moreover, the low cost of Na3 V2 (PO4 )3 /C suggest that this material is a
      promising cathode for large-scale sodium-ion rechargeable batteries. 

PMID- 24014394
TI  - A homozygous mutation in LYRM7/MZM1L associated with early onset encephalopathy,
      lactic acidosis, and severe reduction of mitochondrial complex III activity.
AB  - Mutations in nuclear genes associated with defective complex III (cIII) of the
      mitochondrial respiratory chain are rare, having been found in only two cIII
      assembly factors and, as private changes in single families, three cIII
      structural subunits. Recently, human LYRM7/MZM1L, the ortholog of yeast MZM1, has
      been identified as a new assembly factor for cIII. In a baby patient with early
      onset, severe encephalopathy, lactic acidosis and profound, isolated cIII
      deficiency in skeletal muscle, we identified a disease-segregating homozygous
      mutation (c.73G>A) in LYRM7/MZM1L, predicting a drastic change in a highly
      conserved amino-acid residue (p.Asp25Asn). In a mzm1Delta yeast strain, the
      expression of a mzm1(D25N) mutant allele caused temperature-sensitive respiratory
      growth defect, decreased oxygen consumption, impaired maturation/stabilization of
      the Rieske Fe-S protein, and reduced complex III activity and amount. LYRM7/MZM1L
      is a novel disease gene, causing cIII-defective, early onset, severe
      mitochondrial encephalopathy. 

PMID- 24014395
TI  - A unique amino transfer mechanism for constructing the beta-amino fatty acid
      starter unit in the biosynthesis of the macrolactam antibiotic cremimycin.
AB  - Cremimycin is a 19-membered macrolactam glycoside antibiotic based on three
      distinctive substructures: 1) a beta-amino fatty acid starter moiety, 2) a
      bicyclic macrolactam ring, and 3) a cymarose unit. To elucidate the biosynthetic
      machineries responsible for these three structures, the cremimycin biosynthetic
      gene cluster was identified. The cmi gene cluster consists of 33 open reading
      frames encoding eight polyketide synthases, six deoxysugar biosynthetic enzymes,
      and a characteristic group of five beta-amino-acid-transfer enzymes. Involvement
      of the gene cluster in cremimycin production was confirmed by a gene knockout
      experiment. Further, a feeding experiment demonstrated that 3-aminononanoate is a
      direct precursor of cremimycin. Two characteristic enzymes of the cremimycin-type
      biosynthesis were functionally characterized in vitro. The results showed that a
      putative thioesterase homologue, CmiS1, catalyzes the Michael addition of glycine
      to the beta-position of a non-2-enoic acid thioester, followed by hydrolysis of
      the thioester to give N-carboxymethyl-3-aminononanoate. Subsequently, the
      resultant amino acid was oxidized by a putative FAD-dependent glycine oxidase
      homologue, CmiS2, to produce 3-aminononanoate and glyoxylate. This represents a
      unique amino transfer mechanism for beta-amino acid biosynthesis. 

PMID- 24014396
TI  - Introduction: sirtuins in aging and diseases.
AB  - Over the past 15 years, the number of papers published on sirtuins has exploded.
      The initial link between sirtuins and aging comes from studies in yeast, in which
      it was shown that the life span of yeast mother cells (replicative aging) was
      proportional to the SIR2 gene dosage. Subsequent studies have shown that SIR2
      homologs also slow aging in C. elegans, Drosophila, and mice. An important
      insight into the function of sirtuins came from the finding that yeast Sir2p and
      mammalian SIRT1 are NAD(+)-dependent protein deacetylases. In mammals, there are
      seven sirtuins (SIRT1-7). Their functions do not appear to be redundant, in part
      because three are primarily nuclear (SIRT1, 6, and 7), three are mitochondrial
      (SIRT3, 4, and 5), and one is cytoplasmic (SIRT2). The past decade has provided
      an avalanche of data showing deacetylation of many key transcription factors. In
      this chapter, I will address the evidence that sirtuins mediate the effects of CR
      on physiology and will then turn to the evidence of a relationship between
      sirtuins and aging and life span. Finally, I will discuss the roles of sirtuins
      in diseases of aging and the prospects of translating these findings to novel
      therapeutic strategies to treat major diseases.

PMID- 24014397
TI  - Sirtuins in yeast: phenotypes and tools.
AB  - Originally discovered as a transcriptional silencing protein, SIR2 was later
      linked to yeast replicative aging and the rest was history. Sir2p is now known to
      be a member of a class of protein deacetylases with a unique enzymatic activity
      coupling the deacetylation event to NAD(+) hydrolysis. While still incompletely
      understood, the mechanism by which Sir2p modulates yeast aging is linked to
      inhibition of rDNA recombination. Here we describe phenotypes associated with
      yeast Sirtuins and assays used to monitor Sirtuin function in yeast, including
      the replicative aging assay. 

PMID- 24014398
TI  - C. elegans sirtuins.
AB  - The nematode Caenorhabditis elegans (C. elegans) has four Sir2 paralogs, sir-2.1,
      sir-2.2, sir-2.3, and sir-2.4. Thus far, most of the research tools to study worm
      sirtuins have been developed for sir-2.1, due to its homology to yeast SIR2 and
      human SIRT1. Here, we have compiled a listing of the currently available strains
      (including both loss-of-function alleles and transgenics), antibodies, and RNAi
      constructs relevant to studies on all C. elegans sirtuin family members. We also
      describe the methods used in the analysis of C. elegans sirtuin function,
      including life span analysis, various stress-resistance assays, and fat content
      analysis and provide an overview of all phenotypic data relevant to C. elegans
      sir-2.1. 

PMID- 24014399
TI  - Genetic and biochemical tools for investigating sirtuin function in Drosophila
      melanogaster.
AB  - Drosophila melanogaster is one of the most widely used genetic model systems in
      biology. The ease of working in an invertebrate model system allows the design
      and execution of many experiments that would be infeasible in a vertebrate model.
      Although the strength of the fly as a model system lies primarily in the ease of
      genetic manipulation, it is flexible enough that biochemical and proteomic
      approaches can also be used to build a more comprehensive study. Here we present
      a pair of complementary protocols that we have used to examine sirtuin biology in
      Drosophila. First, we describe our protocol for measuring lifespan in flies
      expressing a gene of interest under the inducible control of the Gene-Switch
      system. Finally, we describe a method for performing chromatin
      immunoprecipitation on adult flies, including some of the difficulties associated
      with using this technique in chitinous tissue.

PMID- 24014400
TI  - Generating mammalian sirtuin tools for protein-interaction analysis.
AB  - The sirtuins are a family of NAD(+)-dependent deacylases with important effects
      on aging, cancer, and metabolism. Sirtuins exert their biological effects by
      catalyzing deacetylation and/or deacylation reactions in which Acyl groups are
      removed from lysine residues of specific proteins. A current challenge is to
      identify specific sirtuin target proteins against the high background of
      acetylated proteins recently identified by proteomic surveys. New evidence
      indicates that bona fide sirtuin substrate proteins form stable physical
      associations with their sirtuin regulator. Therefore, identification of sirtuin
      interacting proteins could be a useful aid in focusing the search for substrates.
      Described here is a method for identifying sirtuin protein interactors. Employing
      basic techniques of molecular cloning and immunochemistry, the method describes
      the generation of mammalian sirtuin protein expression plasmids and their use to
      overexpress and immunoprecipitate sirtuins with their interacting partners. Also
      described is the use of the Database for Annotation, Visualization, and
      Integrated Discovery for interpreting the sirtuin protein-interaction data
      obtained.

PMID- 24014401
TI  - Mass spectrometry-based detection of protein acetylation.
AB  - Improved sample preparation techniques and increasingly sensitive mass
      spectrometry (MS) analysis have revolutionized the study of protein post
      translational modifications (PTMs) (Rush et al., Nat Biotechnol 23:94-101, 2005).
      Here, we describe a general approach for immunopurification and MS-based
      identification of acetylated proteins in biological samples. This approach is
      useful to characterize changes in the acetylome in response to biological
      interventions (Schwer et al., Aging Cell 8:604-606, 2009). 

PMID- 24014402
TI  - SILAC-based quantification of Sirt1-responsive lysine acetylome.
AB  - Stable Isotope Labeling by Amino acids in Cell culture (SILAC) is one of the in
      vivo metabolic labeling methods widely used for dynamic analysis of protein
      modifications. Here, we describe a general approach to applying SILAC, in
      combination with affinity enrichment of acetyllysine peptides and mass
      spectrometry, to study the dynamic changes of the Lysine acetylome in response to
      Sirt1. The method should be applicable to quantify changes to other post
      translational modifications in diverse cellular systems. 

PMID- 24014403
TI  - Targeted quantitation of acetylated lysine peptides by selected reaction
      monitoring mass spectrometry.
AB  - Mass spectrometry (MS) allows for the large-scale identification of multiple
      peptide analytes in complex mixtures. However, the low abundance of acetylated
      peptides in the overall mixture requires an enrichment step. After enrichment,
      the resulting acetylated peptides of interest can be quantitated using selected
      reaction monitoring (SRM)-MS with stable isotope dilution. Here, we describe the
      enrichment of lysine acetylated peptides from typsin digested mouse liver
      mitochondria, and the targeted quantitation of a known lysine acetylation site in
      succinate dehydrogenase A using SRM-MS on a triple quadrupole instrument. 

PMID- 24014404
TI  - Identification of deacetylase substrates with the biotin switch approach.
AB  - The identification of lysine-acetylated proteins and deacetylase substrates has
      primarily relied on protein immune-affinity techniques with antibodies that
      recognize acetylated lysine residues (Kac antibodies). While these antibody-based
      techniques are continuously improving, they can be limited by the narrow and many
      times unknown epitope specificity of Kac antibodies. An alternative approach is
      the biotin switch capture of deacetylated proteins. Similar in part to other
      biotin switch methodologies, this technique relies on the blocking of native
      lysine residues and removal of the modification of interest in vitro, after which
      the newly deacetylated proteins can be captured and identified by mass
      spectrometry (MS). In this chapter, we cover the essential steps of the
      procedure, highlight key points in the assay to reduce false positive protein
      identification, and discuss the quantitative MS methods useful for identifying
      the captured deacetylase substrates. We also discuss potential strategies and
      future improvements to overcome current limitations of the assay. 

PMID- 24014405
TI  - Assaying chromatin sirtuins.
AB  - Most of the sirtuins' nuclear substrates identified so far are histones or other
      chromatin-associated proteins and, thus, it is of special relevance the
      development of good biochemical techniques to analyze the biology of these
      proteins in the context of chromatin. Here, we describe several of the chromatin
      based techniques to identify sirtuins' substrates, including a chromatin
      immunoprecipitation (ChIP) protocol, an acid-extraction protocol, and a
      nucleosomal immunoprecipitation protocol to analyze putative sirtuin chromatin
      interactors. 

PMID- 24014407
TI  - Detecting sirtuin-catalyzed deacylation reactions using 32P-labeled NAD and thin
      layer chromatography.
AB  - Sirtuins are a class of enzymes with important functions in regulation aging,
      metabolism, and genome stability. They were originally known as nicotinamide
      adenine dinucleotide (NAD)-dependent protein lysine deacetylases. However,
      recently it has been discovered that certain sirtuins with weak deacetylase
      activity also hydrolyze novel acyl lysine modifications. These findings indicate
      that other sirtuins with weak deacetylase activity may also possess novel
      activities on unknown protein posttranslational modifications. Analytical methods
      that can help to identify new activity of sirtuins and new acyl lysine
      modifications are thus needed. Here we describe a sensitive method that uses
      (32)P-labeled NAD and thin-layer chromatography to detect sirtuin-catalyzed
      deacylation reactions. This method can help to discover new acyl lysine
      modifications that can be removed by novel sirtuin activities. 

PMID- 24014406
TI  - Measurement of sirtuin enzyme activity using a substrate-agnostic fluorometric
      nicotinamide assay.
AB  - The sirtuins are NAD(+)-dependent, multifunctional lysine deacylases that play
      key roles in cellular homeostasis. They are increasingly being found to target a
      variety of substrates including acetyl-, butyryl-, malonyl-, and succinyl
      lysines. Early assays for measuring sirtuin activity in vitro were criticized for
      their use of fluorophores on the peptide substrates used, which may alter the
      results obtained and not be representative of the in vivo situation. We describe
      a new protocol for the measurement of sirtuin activity by detecting the
      production of nicotinamide (NAM). The assay is amenable to any substrate and any
      modification removed by sirtuins. The assay may also be used to measure
      glycohydrolase (e.g., CD38) and ADP-ribosyltransferase activity (e.g., mARTs and
      PARPs).

PMID- 24014408
TI  - Chemical acetylation and deacetylation.
AB  - Lysine acetylation is an important posttranslational modification known to alter
      protein structure and function. Understanding the mechanisms involved in
      regulating protein acetylation remains a key factor in elucidating what role this
      modification plays in numerous disease pathologies. Here, we describe an in vitro
      strategy to examine the site-specific deacetylation of proteins utilizing the
      chemical acetylation of protein lysine residues via acetic anhydride. The impact
      of chemical acetylation on protein lysine residues is characterized by native gel
      electrophoresis and Western blotting. Acetyl-Lys modifications are then examined
      for deacetylation using a SIRT3 deacetylase activity assay and followed by stable
      isotope dilution mass spectrometry.

PMID- 24014409
TI  - Accurate measurement of nicotinamide adenine dinucleotide (NAD+) with high
      performance liquid chromatography.
AB  - Nicotinamide adenine dinucleotide (NAD(+)) plays a critical role in regulating
      numerous biological and physiological pathways including metabolism,
      inflammation, cancer, and aging in mammals. Here we describe a highly
      quantitative method with reverse-phase high-performance liquid chromatography
      (HPLC) for the determination of NAD(+) levels in cells and tissues. This
      methodology provides accurate, reliable, and reproducible results of NAD(+)
      measurement, which enables us to analyze various pathophysiological changes in
      NAD(+) levels in vitro and in vivo. 

PMID- 24014410
TI  - In vivo measurement of the acetylation state of sirtuin substrates as a proxy for
      sirtuin activity.
AB  - Evaluating the precise catalytic activity of sirtuin proteins in vivo is a
      challenging endeavor. Enzymological methods, including those employed in
      commercially available kits, require the isolation of immunopurified protein from
      cells or tissues, which can perturb regulatory protein-protein interactions as
      well as remove the enzyme from the reaction-altering effects of intracellular
      NAD(+), nicotinamide, and O-acetyl-ADP ribose concentrations. As such, the
      measurement of the steady state acetylation status of select sirtuin substrates
      in vivo remains an important tool for evaluating changes in sirtuin activity.
      Here, we describe how to perform the analysis of the acetylation status of key
      SIRT1 and SIRT3 targets in rodent tissues and cultured cells. 

PMID- 24014411
TI  - Oxygen flux analysis to understand the biological function of sirtuins.
AB  - The sirtuins are a family of highly conserved NAD(+)-dependent lysine deacylases
      with important roles in metabolic regulation. Of the seven mammalian sirtuins,
      three localize to the mitochondria: SIRT3, SIRT4, and SIRT5. Mitochondrial
      sirtuins are crucial regulators of the metabolic network that controls energy
      homeostasis and impacts cancer, obesity, diabetes, mitochondrial diseases,
      metabolic disorders, and many other human diseases of aging. To best study the
      mitochondrial function of the sirtuins, we have employed an oxygen flux analyzer
      as a tool to track and record the extracellular oxygen consumption rate and
      acidification rate that reflects mitochondrial respiration and glycolysis,
      respectfully. Here we described the methods using this assay to study the
      substrate utilization and mitochondrial function in a human hepatocellular
      carcinoma cell line, Huh7. Additionally, we have generated a stable SIRT4 knocked
      down Huh7 cell line. With this cell line, we evaluated how the absence of SIRT4
      affects mitochondrial function, glucose utilization, glutamine oxidation, and
      fatty acid oxidation in these cells.

PMID- 24014412
TI  - The emerging links between sirtuins and autophagy.
AB  - Evidence suggests a role for acetylation and deacetylation in regulating
      autophagy. In this chapter, we describe the methods useful for understanding this
      important connection. In particular, we discuss methods for the measurements of
      sirtuin deacetylase activity, in vivo acetylation detection, and the common
      assays used to monitor both autophagy and the more selective process of
      mitophagy.

PMID- 24014413
TI  - Methods to study the role of sirtuins in genome stability.
AB  - One of the most important roles of Sirtuins is to ensure the maintenance of
      genome integrity under stress conditions. In this chapter, we provide a
      methodology to study this role of Sirtuins at two different levels: detection of
      genomic instability (with the Neutral Comet Assay) and study of Sirtuin dynamics
      in chromatin under stress conditions (by isolating insoluble chromatin
      fractions). 

PMID- 24014414
TI  - Circadian measurements of sirtuin biology.
AB  - Many of our behavioral and physiological processes display daily oscillations
      that are under the control of the circadian clock. The core molecular clock
      network is present in both the brain and peripheral tissues and is composed of a
      complex series of interlocking transcriptional/translational feedback loops that
      oscillate with a periodicity of ~24 h. Recent evidence has implicated NAD(+)
      biosynthesis and the sirtuin family of NAD(+)-dependent protein deacetylases as
      part of a novel feedback loop within the core clock network, findings which
      underscore the importance of taking circadian timing into consideration when
      designing and interpreting metabolic studies, particularly in regard to sirtuin
      biology. Thus, this chapter introduces both in vivo and in vitro circadian
      methods to analyze various sirtuin-related endpoints across the light-dark cycle
      and discusses the transcriptional, biochemical, and physiological outputs of the
      clock. 

PMID- 24014415
TI  - Utilizing calorie restriction to evaluate the role of sirtuins in healthspan and
      lifespan of mice.
AB  - Calorie restriction is the most powerful method currently known to delay aging
      associated disease and extend lifespan. Use of this technique in combination with
      genetic models has led to identification of key metabolic regulators of lifespan.
      Limiting energy availability by restricting caloric intake leads to
      redistribution of energy expenditure and storage. The signaling required for
      these metabolic changes is mediated in part by the sirtuins at both the
      posttranslational and transcriptional levels, and consequently, sirtuins are
      recognized as instigating factors in the regulation of lifespan. This family of
      class III protein deacetylases is responsible for directing energy regulation
      based on NAD(+) availability. However, there are many effectors of NAD(+)
      availability, and hence sirtuin action, that should be considered when performing
      experiments using calorie restriction. The methods outlined in this chapter are
      intended to provide a guide to help the aging community to use and interpret
      experimental calorie restriction properly. The importance of healthspan and the
      use of repeated measures to assess metabolic health during lifespan experiments
      are strongly emphasized.

PMID- 24014416
TI  - Birth defects associated with perturbations in preimplantation, gastrulation, and
      axis extension: from conjoined twinning to caudal dysgenesis.
AB  - Congenital malformations represent approximately 3 in 100 live births within the
      human population. Understanding their pathogenesis and ultimately formulating
      effective treatments are underpinned by knowledge of the events and factors that
      regulate normal embryonic development. Studies in model organisms, primarily in
      the mouse, the most prominent genetically tractable mammalian model, have
      equipped us with a rudimentary understanding of mammalian development from early
      lineage commitment to morphogenetic processes. In this way, information provided
      by studies in the mouse can, in some cases, be used to draw parallels with other
      mammals, including human. Here, we provide an overview of our current
      understanding of the general sequence of developmental events from early cell
      cleavages to gastrulation and axis extension occurring in human embryos. We will
      also review some of the rare birth defects occurring at these stages, in
      particular those resulting in conjoined twinning or caudal dysgenesis.

PMID- 24014417
TI  - Neocortical neurogenesis and neuronal migration.
AB  - The neocortex, the evolutionarily newest part of the cerebral cortex, controls
      nearly all aspects of behavior, including perception, language, and decision
      making. It contains an immense number of neurons that can be broadly divided into
      two groups, excitatory neurons and inhibitory interneurons. These neurons are
      predominantly produced through extensive progenitor cell divisions during the
      embryonic stages. Moreover, they are not randomly dispersed, but spatially
      organized into horizontal layers that are essential for neocortex function. The
      formation of this laminar structure requires exquisite control of neuronal
      migration from their birthplace to their final destination. Extensive research
      over the past decade has greatly advanced our understanding of the production and
      migration of both excitatory neurons and inhibitory interneurons in the
      developing neocortex. In this review, we aim to give an overview on the molecular
      and cellular processes of neocortical neurogenesis and neuronal migration.

PMID- 24014419
TI  - Neural induction and early patterning in vertebrates.
AB  - In vertebrates, the development of the nervous system is triggered by signals
      from a powerful 'organizing' region of the early embryo during gastrulation. This
      phenomenon--neural induction--was originally discovered and given conceptual
      definition by experimental embryologists working with amphibian embryos. Work on
      the molecular circuitry underlying neural induction, also in the same model
      system, demonstrated that elimination of ongoing transforming growth factor-beta
      (TGFbeta) signaling in the ectoderm is the hallmark of anterior neural-fate
      acquisition. This observation is the basis of the 'default' model of neural
      induction. Endogenous neural inducers are secreted proteins that act to inhibit
      TGFbeta ligands in the dorsal ectoderm. In the ventral ectoderm, where the
      signaling ligands escape the inhibitors, a non-neural fate is induced. Inhibition
      of the TGFbeta pathway has now been demonstrated to be sufficient to directly
      induce neural fate in mammalian embryos as well as pluripotent mouse and human
      embryonic stem cells. Hence the molecular process that delineates neural from non
      neural ectoderm is conserved across a broad range of organisms in the
      evolutionary tree. The availability of embryonic stem cells from mouse, primates,
      and humans will facilitate further understanding of the role of signaling
      pathways and their downstream mediators in neural induction in vertebrate
      embryos.

PMID- 24014418
TI  - Genetic causes of microcephaly and lessons for neuronal development.
AB  - The study of human developmental microcephaly is providing important insights
      into brain development. It has become clear that developmental microcephalies are
      associated with abnormalities in cellular production, and that the
      pathophysiology of microcephaly provides remarkable insights into how the brain
      generates the proper number of neurons that determine brain size. Most of the
      genetic causes of 'primary' developmental microcephaly (i.e., not associated with
      other syndromic features) are associated with centrosomal abnormalities. In
      addition to other functions, centrosomal proteins control the mitotic spindle,
      which is essential for normal cell proliferation during mitosis. However, the
      brain is often uniquely affected when microcephaly genes are mutated implying
      special centrosomal-related functions in neuronal production. Although models
      explaining how this could occur have some compelling data, they are not without
      controversy. Interestingly, some of the microcephaly genes show evidence that
      they were targets of evolutionary selection in primates and human ancestors,
      suggesting potential evolutionary roles in controlling neuronal number and brain
      volume across species. Mutations in DNA repair pathway genes also lead to
      microcephaly. Double-stranded DNA breaks appear to be a prominent type of damage
      that needs to be repaired during brain development, yet why defects in DNA repair
      affect the brain preferentially and if DNA repair relates to centrosome function,
      are not clearly understood.

PMID- 24014421
TI  - Notch signaling in the pancreas: patterning and cell fate specification.
AB  - Notch signaling is an evolutionarily conserved mechanism adapted to control
      binary fate decisions. The first evidence of Notch in pancreatic development
      focused on its critical role in controlling endocrine fate decisions. Since then,
      we have come to understand that this signaling system operates iteratively in the
      pancreas, and is not limited to the control of endocrine fate decision. Notch
      appears to play a role in early organ development, then during organ domain
      patterning, and only during a final refinement process, in the control of
      terminal cell fates. In so doing, Notch receptors and their ligands are under the
      influence of a wealth of genetic components that together help orchestrate the
      building of a complex, glandular organ.

PMID- 24014424
TI  - Total deglovement of the fourth digit due to ring avulsion injury.

PMID- 24014420
TI  - Cardiac outflow tract anomalies.
AB  - The mature outflow tract (OFT) is, in basic terms, a short conduit. It is a
      simple, although vital, connection situated between contracting muscular heart
      chambers and a vast embryonic vascular network. Unfortunately, it is also a focal
      point underlying many multifactorial congenital heart defects (CHDs). Through the
      use of various animal models combined with human genetic investigations, we are
      beginning to comprehend the molecular and cellular framework that controls OFT
      morphogenesis. Clear roles of neural crest cells (NCC) and second heart field
      (SHF) derivatives have been established during OFT formation and remodeling. The
      challenge now is to determine how the SHF and cardiac NCC interact, the complex
      reciprocal signaling that appears to be occurring at various stages of OFT
      morphogenesis, and finally how endocardial progenitors and primary heart field
      (PHF) communicate with both these colonizing extra-cardiac lineages. Although we
      are beginning to understand that this dance of progenitor populations is
      wonderfully intricate, the underlying pathogenesis and the spatiotemporal cell
      lineage interactions remain to be fully elucidated. What is now clear is that OFT
      alignment and septation are independent processes, invested via separate SHF and
      cardiac neural crest (CNC) lineages. This review will focus on our current
      understanding of the respective contributions of the SHF and CNC lineage during
      OFT development and pathogenesis.

PMID- 24014423
TI  - Does bone resorption stimulate periosteal expansion? A cross-sectional analysis
      of beta-C-telopeptides of type I collagen (CTX), genetic markers of the RANKL
      pathway, and periosteal circumference as measured by pQCT.
AB  - We hypothesized that bone resorption acts to increase bone strength through
      stimulation of periosteal expansion. Hence, we examined whether bone resorption,
      as reflected by serum beta-C-telopeptides of type I collagen (CTX), is positively
      associated with periosteal circumference (PC), in contrast to inverse
      associations with parameters related to bone remodeling such as cortical bone
      mineral density (BMDC ). CTX and mid-tibial peripheral quantitative computed
      tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years)
      from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were
      adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass,
      and height. CTX was positively related to PC (beta=0.19 [0.13, 0.24])
      (coefficient=SD change per SD increase in CTX, 95% confidence interval)] but
      inversely associated with BMDC (beta=-0.46 [-0.52,-0.40]) and cortical thickness
      [beta=-0.11 (-0.18, -0.03)]. CTX was positively related to bone strength as
      reflected by the strength-strain index (SSI) (beta=0.09 [0.03, 0.14]). To examine
      the causal nature of this relationship, we then analyzed whether single
      nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to
      reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants
      within or proximal to genes encoding receptor activator of NF-kappaB (RANK), RANK
      ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search.
      Six of the 15 alleles that were inversely related to BMD were positively related
      to CTX (p<0.05 cut-off) (n=2379). Subsequently, we performed a meta-analysis of
      associations between these SNPs and PC in ALSPAC (n=3382), Gothenburg
      Osteoporosis and Obesity Determinants (GOOD) (n=938), and the Young Finns Study
      (YFS) (n=1558). Five of the 15 alleles that were inversely related to BMD were
      positively related to PC (p<0.05 cut-off). We conclude that despite having lower
      BMD, individuals with a genetic predisposition to higher bone resorption have
      greater bone size, suggesting that higher bone resorption is permissive for
      greater periosteal expansion.

PMID- 24014425
TI  - Hypereosinophilic syndrome associated with ulcerative colitis presenting with
      recurrent Loeffler's endocarditis and left ventricular thrombus treated
      successfully with immune suppressive therapy and anticoagulation.
AB  - We reported a case of a 28-year-old Caucasian woman with hypereosinophilic
      syndrome (HES) associated with ulcerative colitis who presented on separate
      occasions with Loeffler's endocarditis. She was admitted in 2008 with fever,
      headache, confusion and visual loss. Diagnostic workup uncovered an eosinophilia
      of 3.1*109/L and major ECG abnormalities. Subsequent echocardiography revealed
      left ventricular wall motion abnormalities with mural thrombus. MRI brain scan
      showed multiple white matter lesions consistent with acute infarcts. She
      recovered rapidly with corticosteroids and anticoagulation. Four years later she
      re-presented with headache, fatigue and an eosinophilia of 13.4*109/L. This
      occurred 3 months after cessation of immunosuppression and within 12 months of
      total colectomy for fulminant ulcerative colitis. Echocardiography was suggestive
      of hypereosinophilic endomyocardial fibrosis with left ventricular thrombus.
      Anticoagulation and corticosteroids were resumed with good effect. This report
      highlights the findings, treatment and outcome of ulcerative colitis-associated
      HES manifesting as recurrent Loeffler's endocarditis.

PMID- 24014422
TI  - Retinal differentiation in Drosophila.
AB  - Drosophila eye development has been extensively studied, due to the ease of
      genetic screens for mutations disrupting this process. The eye imaginal disc is
      specified during embryonic and larval development by the Pax6 homolog Eyeless and
      a network of downstream transcription factors. Expression of these factors is
      regulated by signaling molecules and also indirectly by growth of the eye disc.
      Differentiation of photoreceptor clusters initiates in the third larval instar at
      the posterior of the eye disc and progresses anteriorly, driven by the secreted
      protein Hedgehog. Within each cluster, the combined activities of Hedgehog
      signaling and Notch-mediated lateral inhibition induce and refine the expression
      of the transcription factor Atonal, which specifies the founding R8 photoreceptor
      of each ommatidium. Seven additional photoreceptors, followed by cone and pigment
      cells, are successively recruited by the signaling molecules Spitz, Delta, and
      Bride of sevenless. Combinations of these signals and of intrinsic transcription
      factors give each ommatidial cell its specific identity. During the pupal stages,
      rhodopsins are expressed, and the photoreceptors and accessory cells take on
      their final positions and morphologies to form the adult retina. Over the past
      few decades, the genetic analysis of this small number of cell types arranged in
      a repetitive structure has allowed a remarkably detailed understanding of the
      basic mechanisms controlling cell differentiation and morphological
      rearrangement.

PMID- 24014426
TI  - Evidence for dysregulation of genome-wide recombination in oocytes with
      nondisjoined chromosomes 21.
AB  - In oocytes with nondisjoined chromosomes 21 due to a meiosis I (MI) error,
      recombination is significantly reduced along chromosome 21; several lines of
      evidence indicate that this contributes to the nondisjunction event. A pilot
      study found evidence that these oocytes also have reduced recombination genome
      wide when compared with controls. This suggests that factors that act globally
      may be contributing to the reduced recombination on chromosome 21, and hence, the
      nondisjunction event. To identify the source of these factors, we examined two
      levels of recombination count regulation in oocytes: (i) regulation at the
      maternal level that leads to correlation in genome-wide recombination across her
      oocytes and (ii) regulation at the oocyte level that leads to correlation in
      recombination count among the chromosomes of an oocyte. We sought to determine
      whether either of these properties was altered in oocytes with an MI error. As it
      relates to maternal regulation, we found that both oocytes with an MI error (N =
      94) and their siblings (N = 64) had reduced recombination when compared with
      controls (N = 2723). At the oocyte level, we found that the correlation in
      recombination count among the chromosomes of an oocyte is reduced in oocytes with
      MI errors compared with that of their siblings or controls. These results suggest
      that regulation at the maternal level predisposes MI error oocytes to reduced
      levels of recombination, but additional oocyte-specific dysregulation contributes
      to the nondisjunction event.

PMID- 24014428
TI  - The catalytic mechanism of protein phosphatase 5 established by DFT calculations.
AB  - In order to elucidate the catalytic mechanism of the Mn-Mn containing
      serine/threonine protein phosphatase 5 (PP5), we present a density functional
      theory study with a cluster model approach. According to our results, the
      reaction occurs through an in-line concerted transition state with an energy of
      15.8 kcal mol(-1) , and no intermediates are formed. The important role played by
      His304 and Asp274 as stabilizers of the leaving group has been shown, whereas the
      role played by the metal ions seems to be mostly electrostatic. The indispensable
      requirement of having a neutral active center has been demonstrated by testing
      different protonation states of the cluster model. We have shown also the
      importance of describing properly the electronic configuration of the Mn-Mn
      binuclear centers.

PMID- 24014427
TI  - Epigenome-wide DNA methylation landscape of melanoma progression to brain
      metastasis reveals aberrations on homeobox D cluster associated with prognosis.
AB  - Melanoma brain metastasis (MBM) represents a frequent complication of cutaneous
      melanoma. Despite aggressive multi-modality therapy, patients with MBM often have
      a survival rate of <1 year. Alteration in DNA methylation is a major hallmark of
      tumor progression and metastasis; however, it remains largely unexplored in MBM.
      In this study, we generated a comprehensive DNA methylation landscape through the
      use of genome-wide copy number, DNA methylation and gene expression data
      integrative analysis of melanoma progression to MBM. A progressive genome-wide
      demethylation in low CpG density and an increase in methylation level of CpG
      islands according to melanoma progression were observed. MBM-specific partially
      methylated domains (PMDs) affecting key brain developmental processes were
      identified. Differentially methylated CpG sites between MBM and lymph node
      metastasis (LNM) from patients with good prognosis were identified. Among the
      most significantly affected genes were the HOX family members. DNA methylation of
      HOXD9 gene promoter affected transcript and protein expression and was
      significantly higher in MBM than that in early stages. A MBM-specific PMD was
      identified in this region. Low methylation level of this region was associated
      with active HOXD9 expression, open chromatin and histone modifications associated
      with active transcription. Demethylating agent induced HOXD9 expression in
      melanoma cell lines. The clinical relevance of this finding was verified in an
      independent large cohort of melanomas (n = 145). Patients with HOXD9
      hypermethylation in LNM had poorer disease-free and overall survival. This
      epigenome-wide study identified novel methylated genes with functional and
      clinical implications for MBM patients. 

PMID- 24014429
TI  - Geranylation of cyclic dipeptides by the dimethylallyl transferase AnaPT
      resulting in a shift of prenylation position on the indole ring.
AB  - The dimethylallyl transferase AnaPT from Neosartorya fischeri is involved in the
      biosynthesis of acetylaszonalenin and catalyses the regioselective and
      stereospecific C3alpha-prenylation of (R)-benzodiazepinedione in the presence of
      dimethylallyl diphosphate. This enzyme also converts several tryptophan
      containing cyclic dipeptides to C3alpha-prenylated indolines. In this study, we
      demonstrate the geranylation of (R)-benzodiazepinedione and five other cyclic
      dipeptides by AnaPT in the presence of geranyl diphosphate (GPP). Interestingly,
      structure elucidation by NMR and MS analyses revealed that, with GPP, the geranyl
      moiety is attached to C-6 or C-7 rather than C-3 of the indole ring of the enzyme
      products. For (R)-benzodiazepinedione, one dominant C6-geranylated derivative was
      obtained, whereas the other five substrates yielded both C6- and C7-geranylated
      products. Neither acceptance of GPP by a dimethylallyl transferase from the
      dimethylallyltryptophan synthase superfamily, nor the alkylation shift from C-3
      to the benzene ring of the indole nucleus has been reported previously. 

PMID- 24014430
TI  - Hantzsch based macrocyclization approach for the synthesis of thiazole containing
      cyclopeptides.
AB  - An innovative macrocyclization approach via high-yielding solid-phase
      intramolecular thioalkylation reaction is described. The reaction of S
      nucleophiles with newly generated N-terminal 4-chloromethyl thiazoles leads to
      the desired cyclic products in high purities and good yields.

PMID- 24014431
TI  - The chemical synthesis of alpha-conotoxins and structurally modified analogs with
      enhanced biological stability.
AB  - alpha-Conotoxins are peptide neurotoxins isolated from the venom ducts of
      carnivorous marine cone snails that exhibit exquisite pharmacological potency and
      selectivity for various nicotinic acetylcholine receptor subtypes. As such, they
      are important research tools and drug leads for treating various diseases of the
      central nervous system, including pain and tobacco addiction. Despite their
      therapeutic potential, the chemical synthesis of alpha-conotoxins for use in
      structure-activity relationship studies is complicated by the possibility of
      three disulfide bond isomers, where inefficient folding methods can lead to a
      poor recovery of the pharmacologically active isomer. In order to achieve higher
      yields of the native isomer, especially in high-throughput syntheses it is
      necessary to select appropriate oxidative folding conditions. Moreover, the poor
      biochemical stability exhibited by alpha-conotoxins limits their general
      therapeutic applicability in vivo. Numerous strategies to enhance their stability
      including the substitution of disulfide bond with diselenide bond and N-to-C
      cyclization via an oligopeptide spacer have successfully overcome these
      limitations. This chapter describes methods for performing both selective and
      nonselective disulfide bond oxidation strategies for controlling the yields and
      formation of alpha-conotoxin disulfide bond isomers, as well as methods for the
      production of highly stable diselenide-containing and N-to-C cyclized conotoxin
      analogs. 

PMID- 24014432
TI  - Synthesis of AApeptides.
AB  - The creation and development of nonnatural peptidomimetics has become an area of
      increasing significance in bioorganic and chemical biology. A wide range of new
      peptide mimics with novel structures and functions are urgently needed to be
      explored in order to identify potential drug candidates and targeted probes, and
      to study protein functions. AApeptides are a new class of peptide mimics based on
      chiral PNA backbone. They are resistant to proteolytic degradation and have
      limitless potential for diversification. They have been found to have a wide
      variety of biological applications including cellular translocation, disruption
      of protein-protein interactions, formation of nanostructures, antimicrobial
      activity, etc. The synthesis of AApeptides is modular and straightforward. In
      this chapter, methods for the synthesis of AApeptides (including different
      subclasses) are described.

PMID- 24014433
TI  - Peptoids and peptide-peptoid hybrid biopolymers as peptidomimetics.
AB  - Peptoids (oligomers of N-substituted glycine residues) and peptide-peptoid hybrid
      polymers (peptomers) are interesting classes of compounds mimicking structure and
      function of biologically active peptides. The oligomeric peptidomimetics such as
      peptoids are particularly important compounds since they provide access to an
      enormous molecular diversity, by variation of the building blocks. The modular
      structure of peptoids, ease of synthesis, and high compatibility with existing
      peptide chemistry synthetic protocols, make peptoids and peptoid-containing
      peptidomimetics ideal tools for structure-activity and drug discovery related
      studies. 

PMID- 24014434
TI  - Synthesis of side chain N,N'-diaminoalkylated derivatives of basic amino acids
      for application in solid-phase peptide synthesis.
AB  - Despite the enormous therapeutic potential, the clinical use of peptides has been
      limited by their poor bioavailability and low stability under physiological
      conditions. Hence, efforts have been undertaken to alter peptide structure in
      ways to improve their pharmacological properties. Inspired by the importance of
      basic amino acids in biological systems and the remarkable versatility displayed
      by lysine during the synthesis of complex peptide scaffolds, this chapter
      describes a simple procedure that enables rapid access to protected N,N'
      diaminoalkylated basic amino acid building blocks suitable for standard solid
      phase peptide synthesis. This procedure allows preparation of symmetrical, as
      well as unsymmetrical, dialkylated amino acid derivatives that can be further
      modified, enhancing their synthetic utility. The suitability of the synthesized
      branched basic amino acid building blocks for use in standard solid-phase peptide
      synthesis has been demonstrated by synthesis of an indolicidin analog in which
      the lysine residue was substituted with its synthetic polyamino derivate. The
      substitution provided indolicidin analog with increase net positive charge, more
      ordered secondary structure in biological membranes mimicking conditions, and
      enhanced antibacterial activity without altering hemolytic activity. Taking into
      consideration the increasing interest for peptides with unusual structural
      features due to their improved biological properties, the described synthesis of
      polyfunctional amino acid building blocks is of particular practical value.

PMID- 24014435
TI  - Study protein folding and aggregation using nonnatural amino acid p
      cyanophenylalanine as a sensitive optical probe.
AB  - Incorporation of nonnatural amino acids with a variety of special side groups
      into protein sequences has substantially expanded the experimental means of
      exploring protein structures and functions. Recently, p-cyanophenylalanine
      (PheCN), the nitrile analogue of phenylalanine, has been used as a novel optical
      probe for protein binding and folding studies. The fluorescence emission of PheCN
      is sensitive to solvent and local environment of the residue, making it a useful
      fluorescent probe of protein structural change at residue-specific resolution.
      Moreover, the utility of PheCN is increased by its ability to excite tryptophan
      fluorescence via the mechanism of fluorescence resonance energy transfer. PheCN
      could be applied to study a variety of biological problems, e.g., protein
      folding/unfolding and protein aggregation. 

PMID- 24014436
TI  - Adamantoylated biologically active small peptides and glycopeptides structurally
      related to the bacterial peptidoglycan.
AB  - A large number of novel synthetic compounds representing smaller parts of
      original peptidoglycan molecules have been synthesized and found to possess
      versatile biological activity, particularly immunomodulating properties. A series
      of compounds containing the adamantyl residues coupled to peptides and
      glycopeptides characteristic for bacterial peptidoglycan was described. The new
      adamantylpeptides and adamantylglycopeptides were prepared starting from N
      protected racemic adamantylglycine and dipeptide L-Ala-D-isoglutamine. The
      adamantyl glycopeptides were obtained by coupling the adamantyltripeptides with
      alpha-D-mannose moiety through spacer molecule of fixed chirality. Since the
      starting material was D,L-(adamantyl-glycine) the condensation products with the
      dipeptide were mixtures of diastereoisomers. The obtained diastereoisomers were
      separated, characterized, and tested for immunostimulating activity. An HPLC
      method for purity testing was developed and adapted for the particular compounds.

PMID- 24014437
TI  - Optimization of physicochemical and pharmacological properties of peptide drugs
      by glycosylation.
AB  - Many biological interactions and functions are mediated by glycans, leading to
      the emerging importance of carbohydrate and glycoconjugate chemistry in the
      design of novel drug therapeutics. In addition to direct effects on biological
      activity, sugar addition appears to alter many physicochemical and
      pharmacological properties of the peptide backbone. Consequently, glycosylation
      has been often used to improve various less than optimal features of peptide drug
      leads.In order to study the effects that naturally occurring and/or nonnatural
      glycans have on peptide drug solubility, conformation, proteolytic resistance,
      membrane permeability, and toxicity, it is essential to have convenient synthetic
      access toward synthesis of glycopeptide analogs. The crucial step in the
      synthesis of glycopeptides is the introduction of the carbohydrate group. The
      preformed glycosyl amino acid building block is the most commonly employed
      approach used in glycopeptide synthesis.In this review, we will describe various
      synthetic approaches to prepare N- and O-glycopeptides bearing simple
      monosaccharides as a tool to improve peptide therapeutic efficacy by
      glycosylation. 

PMID- 24014438
TI  - The Maillard reaction induced modifications of endogenous opioid peptide
      enkephalin.
AB  - Nonenzymatic glycation (Maillard reaction) is a posttranslational modification of
      peptides and proteins by sugars, which, after a cascade of reactions, leads to
      the formation of a complex family of irreversibly changed advanced glycation end
      products (AGE) implicated in the pathogenesis of human diseases. Last reversible
      intermediates of this reaction are Amadori/Heyns compounds formed in
      glucose/fructose induced modification of peptides. The stability of these
      compounds determines the further course of the reaction.To provide information
      concerning the preparation of model systems as well as the fate of glycated
      opioid peptides introduced in the human circulation, the enzymatic (80 % human
      serum) and chemical (PBS) stability of Amadori and Heyns compounds related to the
      endogenous opioid pentapeptides leucine- and methionine-enkephalin (Tyr-Gly-Gly
      Phe-Leu/Met) were investigated. 

PMID- 24014439
TI  - Solid-phase guanidinylation of peptidyl amines compatible with standard Fmoc
      chemistry: formation of monosubstituted guanidines.
AB  - With the growing importance of peptides and peptidomimetics as potential
      therapeutic agents, a continuous synthetic interest has been shown for their
      modification to provide more stable and bioactive analogs. Among many approaches,
      peptide/peptidomimetic guanidinylation offers access to analogs possessing
      functionality with strong basic properties, capable of forming stable
      intermolecular H-bonds, charge pairing, and cation-pi interactions. Therefore,
      guanidinium functional group is considered as an important pharmacophoric
      element. Although a number of methods for solid-phase guanidinylation reactions
      exist, only a few are fully compatible with standard Fmoc solid-phase peptide
      chemistry.In this chapter we summarize the solid-phase guanidinylation methods
      fully compatible with standard Fmoc-synthetic methodology. This includes use of
      direct guanidinylating reagents such as 1-H-pyrazole-1-carboxamidine and
      triflylguanidine, and guanidinylation with di-protected thiourea derivatives in
      combination with promoters such as Mukaiyama's reagent, N-iodosuccinimide, and
      N,N'-diisopropylcarbodiimide.

PMID- 24014441
TI  - Identification of adipokine receptor agonists and turning them to antagonists.
AB  - Receptor-ligand interactions represent one of the most basic processes in
      biological systems. Receptor activation and deactivation induce or prevent a
      series of downstream signaling events that ultimately result in normal or
      abnormal cellular functions. Contemporary biology is in continuous search for the
      identification of novel receptors and their ligands. The adipose tissue
      participates in the regulation of energy homeostasis as an important endocrine
      organ that secretes a number of biologically active adipokines, including leptin
      and adiponectin. A recent discovery and design process for leptin and adiponectin
      receptor response modifier peptides can be generalized to a series of
      transmembrane receptor ligands. A family of 11-13 amino acid residue-long leptin
      receptor (ObR) agonists has been identified by analyzing the effect of peptides
      corresponding to the three presumed active sites of leptin on the growth of
      leptin-responsive cancer cells. In the case of adiponectin, overlapping peptides
      were walked across the entire globular domain of the protein to identify the
      active site and derive adiponectin receptor (AdipoR) agonist peptides. In both
      sets, native residues were replaced by nonnatural analogs to improve the
      pharmacological properties including stability, efficacy and targeting. Later the
      ObR analogs were converted into true ObR antagonists that show antagonist-agonist
      selectivity of 1,000 in cellular assays. The design process of ObR antagonists
      included shortening of the peptide length and incorporating additional nonnatural
      residues. Here I take a look into this receptor agonist and antagonist discovery
      process from a practical point of view. 

PMID- 24014442
TI  - Peptide detection and structure determination in live cells using confocal Raman
      microscopy.
AB  - Peptides are an important class of bioactive compounds that continue to be
      developed for a variety of therapeutic uses. The bioactivity of peptides stems in
      most cases from their ability to enter or bind to the surface of cells to elicit
      a cellular response, and the primary sequence and secondary structure of the
      peptide determine this. Therefore, experimental methods that can provide
      structural information on peptides in live cells are useful for exploring peptide
      structure-activity relationships and metabolism directly within the targeted
      cellular environment. In this chapter we describe an experimental methodology for
      the detection and structure determination of exogenous peptides within living
      cells using confocal Raman microscopy (CRM). CRM is Raman spectroscopy performed
      under a confocal microscope. Raman spectroscopy itself has been applied to the
      study of peptides for several decades and provides a wealth of information,
      including secondary structure via the amide backbone vibrational modes, cysteine
      redox status via the S-S and S-H stretches, and disulfide conformation via the S
      S stretch. The Raman spectra of peptides are dominated by intense bands
      associated with the aromatic ring vibrations of Phe, Tyr, and Trp. The positions
      and intensities of some of these bands are sensitive to the hydrophobicity and pH
      of the peptide environment and thus can potentially be used as intracellular
      probes. Heavy-isotope labeling of aromatic ring side chains shifts the spectral
      positions of the aromatic ring vibrations and enables unambiguous detection of
      the peptide within cells. We employ this method primarily for the study of cell
      penetrating peptides in live cells. However, the method could in principle be
      applied to the study of any type of peptide within any type of cell if the
      intracellular concentration of the peptide reaches high enough levels to enable
      detection. 

PMID- 24014440
TI  - Stabilization of collagen-model, triple-helical peptides for in vitro and in vivo
      applications.
AB  - The triple-helical structure of collagen has been accurately reproduced in
      numerous chemical and recombinant model systems. Triple-helical peptides and
      proteins have found application for dissecting collagen-stabilizing forces,
      isolating receptor- and protein-binding sites in collagen, mechanistic
      examination of collagenolytic proteases, and development of novel biomaterials.
      Introduction of native-like sequences into triple-helical constructs can reduce
      the thermal stability of the triple-helix to below that of the physiological
      environment. In turn, incorporation of nonnative amino acids and/or templates can
      enhance triple-helix stability. We presently describe approaches by which triple
      helical structure can be modulated for use under physiological or near
      physiological conditions. 

PMID- 24014443
TI  - Caution over use of catheter ablation for atrial fibrillation.

PMID- 24014444
TI  - Indian MPs criticise HPV vaccination project for ethical violations.

PMID- 24014445
TI  - Journal agrees to retract paper after university found study was never done.

PMID- 24014446
TI  - Event-related fMRI at 7T reveals overlapping cortical representations for
      adjacent fingertips in S1 of individual subjects.
AB  - Recent fMRI studies of the human primary somatosensory cortex have been able to
      differentiate the cortical representations of different fingertips at a single
      subject level. These studies did not, however, investigate the expected overlap
      in cortical activation due to the stimulation of different fingers. Here, we used
      an event-related design in six subjects at 7 Tesla to explore the overlap in
      cortical responses elicited in S1 by vibrotactile stimulation of the five
      fingertips. We found that all parts of S1 show some degree of spatial overlap
      between the cortical representations of adjacent or even nonadjacent fingertips.
      In S1, the posterior bank of the central sulcus showed less overlap than regions
      in the post-central gyrus, which responded to up to five fingertips. The
      functional properties of these two areas are consistent with the known layout of
      cytoarchitectonically defined subareas, and we speculate that they correspond to
      subarea 3b (S1 proper) and subarea 1, respectively. In contrast with previous
      fMRI studies, however, we did not observe discrete activation clusters that could
      unequivocally be attributed to different subareas of S1. Venous maps based on T2*
      weighted structural images suggest that the observed overlap is not driven by
      extra-vascular contributions from large veins.

PMID- 24014447
TI  - Development and manipulation of spontaneous eye blinking in the first year:
      relationships to context and positive affect.
AB  - The present study explored the development of spontaneous eye blinking (SEB) and
      its relationship to approach-inhibition behavior during the second half of the
      first year. The dopaminergic regulation of SEB in adult primates provides an
      empirical basis for studying blinking in infants, and dopamine's role in infant
      temperament provides justification for examining approach-inhibition
      specifically. A longitudinal design with an experimental manipulation was used to
      examine developmental change in the rate of SEB. Healthy, full-term infants (N =
      74) were observed at 4 and 12 months. Blinking rate was observed during a quiet
      baseline and a randomly assigned stimulus condition. Then, approach-inhibition
      responses were examined as stimulus objects were presented. Experimental
      conditions altered blink rate at both ages, but the effects varied by age and
      stimulus type. At 12 months, individual differences in SEB were associated with
      positive affect during the approach-inhibition task. The divergent effects for
      the cognitive and social conditions suggest that the mechanisms regulating blink
      rate have distinct relationships to these behavioral domains and that these
      undergo changes during the first year.

PMID- 24014449
TI  - Using mutants, knockdowns, and transgenesis to investigate gene function in
      Drosophila.
AB  - The sophisticated genetic techniques available in Drosophila are largely
      responsible for its success as a model organism. One of the most important of
      these is the ability to disrupt gene function in vivo and observe the resulting
      phenotypes. This review considers the ever-increasing repertoire of approaches
      for perturbing the functions of specific genes in flies, ranging from classical
      and transposon-mediated mutageneses to newer techniques, such as homologous
      recombination and RNA interference. Since most genes are used over and over again
      in different contexts during development, many important advances have depended
      on being able to interfere with gene function at specific times or places in the
      developing animal, and a variety of approaches are now available to do this. Most
      of these techniques rely on being able to create genetically modified strains of
      Drosophila and the different methods for generating lines carrying single copy
      transgenic constructs will be described, along with the advantages and
      disadvantages of each approach.

PMID- 24014450
TI  - Chromatin looping and organization at developmentally regulated gene loci.
AB  - Developmentally regulated genes are often controlled by distant enhancers,
      silencers and insulators, to implement their correct transcriptional programs. In
      recent years, the development of 3C and derived techniques (4C, 5C, HiC, ChIA
      PET, etc.) has confirmed that chromatin looping is an important mechanism for the
      transfer of regulatory information in mammalian cells. At many developmentally
      regulated gene loci, transcriptional activation is indeed accompanied by the
      formation of chromatin loops between genes and distant enhancers. Similarly,
      dynamic looping between insulator elements and changes in local 3D organization
      may be observed upon variation in transcriptional activity. Chromatin looping
      also occurs at silent gene loci, where its function remains less understood. In
      lineage-committed cells, partial 3D configurations are detected at loci that are
      activated at later stages. However, these partial configurations usually lack
      promoter-enhancer loops that accompany transcriptional activation, suggesting
      they have structural functions. Definitive evidence for a repressive role of
      chromatin looping is still lacking. Chromatin loops have been reported at
      repressed loci but, alternatively, they may act as a distraction for active
      loops. Together, these mechanisms allow fine-tuning of regulatory programs, thus
      providing further diversity in the transcriptional control of developmentally
      regulated gene loci.

PMID- 24014448
TI  - Kidney organogenesis in the zebrafish: insights into vertebrate nephrogenesis and
      regeneration.
AB  - Vertebrates form a progressive series of up to three kidney organs during
      development-the pronephros, mesonephros, and metanephros. Each kidney derives
      from the intermediate mesoderm and is comprised of conserved excretory units
      called nephrons. The zebrafish is a powerful model for vertebrate developmental
      genetics, and recent studies have illustrated that zebrafish and mammals share
      numerous similarities in nephron composition and physiology. The zebrafish embryo
      forms an architecturally simple pronephros that has two nephrons, and these
      eventually become a scaffold onto which a mesonephros of several hundred nephrons
      is constructed during larval stages. In adult zebrafish, the mesonephros exhibits
      ongoing nephrogenesis, generating new nephrons from a local pool of renal
      progenitors during periods of growth or following kidney injury. The
      characteristics of the zebrafish pronephros and mesonephros make them genetically
      tractable kidney systems in which to study the functions of renal genes and
      address outstanding questions about the mechanisms of nephrogenesis. Here, we
      provide an overview of the formation and composition of these zebrafish kidney
      organs, and discuss how various zebrafish mutants, gene knockdowns, and
      transgenic models have created frameworks in which to further delineate
      nephrogenesis pathways.

PMID- 24014451
TI  - Differential adhesion in model systems.
AB  - During embryonic development, cells or groups of cells migrate from their
      locations of origin to assume their correct anatomical positions. Intercellular
      adhesion plays an active and instructive role in orchestrating this process.
      Precisely how adhesion provides spatial positioning information is a subject of
      intense interest. In the 1960s, Steinberg proposed the differential adhesion
      hypothesis (DAH) to explain how differences in the intensity of cell adhesion
      could give rise to predictable spatial interactions between different cell types.
      The DAH is grounded in the same set of physical principles governing the
      interaction of immiscible fluids and thus provides a rigorous conceptual
      framework connecting the chemistry of cell adhesion to the physics underlying
      cell and tissue segregation. Testing the DAH required the development of methods
      to measure intercellular cohesion and of assays to accurately assess relative
      spatial position between cells. The DAH has been experimentally verified and
      computationally simulated. Moreover, evidence concerning the role of differential
      adhesion in a number of morphodynamic events is accumulating. It is clear that
      differential adhesion is a major driving force in various aspects of embryonic
      development, but recent studies have also advanced the concept that other
      factors, such as cortical tension and elasticity, may also be involved in fine
      tuning, or even driving the process. It is likely that an interplay between
      adhesion and these other factors co-operate to generate the forces required for
      tissue self-organization.

PMID- 24014453
TI  - Core pathways controlling shoot meristem maintenance.
AB  - Essential to the function of shoot meristems in plants to act as sites of
      continuous organ and tissue formation is the ability of cells within the meristem
      to remain undifferentiated and proliferate indefinitely. These are
      characteristics of the stem cells within meristems that are critical for their
      growth properties. Stem cells are found in tight association with the stem cell
      niche-those cells that signal to maintain stem cells. Shoot meristems are unique
      among stem cell systems in that the stem cell niche is a constantly changing
      population of recent daughter stem cells. Recent progress from Arabidopsis and
      other systems have uncovered a large number of genes with defined roles in
      meristem structure and maintenance. This review will focus on well-studied
      pathways that represent signaling between the stem cells and the niche, that
      prevent ectopic differentiation of stem cells, that regulate the chromatin status
      of stem cell factors, and that reveal intersection of hormone signaling and
      meristem maintenance.

PMID- 24014452
TI  - Development and plasticity of the Drosophila larval neuromuscular junction.
AB  - The Drosophila larval neuromuscular system is relatively simple, containing only
      32 motor neurons in each abdominal hemisegment, and its neuromuscular junctions
      (NMJs) have been studied extensively. NMJ synapses exhibit developmental and
      functional plasticity while displaying stereotyped connectivity. Drosophila Type
      I NMJ synapses are glutamatergic, while the vertebrate NMJ uses acetylcholine as
      its primary neurotransmitter. The larval NMJ synapses use ionotropic glutamate
      receptors (GluRs) that are homologous to AMPA-type GluRs in the mammalian brain,
      and they have postsynaptic scaffolds that resemble those found in mammalian
      postsynaptic densities. These features make the Drosophila neuromuscular system
      an excellent genetic model for the study of excitatory synapses in the mammalian
      central nervous system. The first section of the review presents an overview of
      NMJ development. The second section describes genes that regulate NMJ
      development, including: (1) genes that positively and negatively regulate growth
      of the NMJ, (2) genes required for maintenance of NMJ bouton structure, (3) genes
      that modulate neuronal activity and alter NMJ growth, (4) genes involved in
      transsynaptic signaling at the NMJ. The third section describes genes that
      regulate acute plasticity, focusing on translational regulatory mechanisms. As
      this review is intended for a developmental biology audience, it does not cover
      NMJ electrophysiology in detail, and does not review genes for which mutations
      produce only electrophysiological but no structural phenotypes.

PMID- 24014454
TI  - Set2 mediated H3 lysine 36 methylation: regulation of transcription elongation
      and implications in organismal development.
AB  - Set2 is a RNA polymerase II (RNAPII) associated histone methyltransferase
      involved in the cotranscriptional methylation of the H3 K36 residue (H3K36me). It
      is responsible for multiple degrees of methylation (mono-, di-, and
      trimethylation), each of which has a distinct functional consequence. The extent
      of methylation and its genomic distribution is determined by different factors
      that coordinate to achieve a functional outcome. In yeast, the Set2-mediated
      H3K36me is involved in suppressing histone exchange, preventing hyperacetylation
      and promoting maintenance of well-spaced chromatin structure over the coding
      regions. In metazoans, separation of this enzymatic activity affords greater
      functional diversity extending beyond the control of transcription elongation to
      developmental gene regulation. This review focuses on the molecular aspects of
      the Set2 distribution and function, and discusses the role played by H3 K36
      methyl mark in organismal development.

PMID- 24014456
TI  - Regulation of developmental processes: insights from mass spectrometry-based
      proteomics.
AB  - Mass spectrometry (MS)-based proteomics has become an indispensable tool for
      protein identification and quantification. In this paper, common MS workflows are
      described, with an emphasis on applications of MS-based proteomics in
      developmental biology. Progress has been made in the analysis of proteome changes
      during tissue differentiation and in various genetic perturbations. MS-based
      proteomics has been particularly useful for identifying novel protein
      interactions by affinity purification-mass spectrometry (AP-MS), many of which
      have been subsequently functionally validated and led to the discovery of
      previously unknown modes of developmental regulation. Quantitative proteomics
      approaches can be used to study posttranslational modifications (PTMs) of
      proteins such as phosphorylation, to reveal the dynamics of intracellular signal
      transduction. Integrative approaches combine quantitative MS-based proteomics
      with other high-throughput methods, with the promise of a systems level
      understanding of developmental regulation.

PMID- 24014457
TI  - Boundary formation in the development of the vertebrate hindbrain.
AB  - The formation of a sharp interface of adjacent subdivisions is important for
      establishing the precision of tissue organization, and at specific borders it
      serves to organize key signaling centers. We discuss studies of vertebrate
      hindbrain development that have given important insights into mechanisms that
      underlie the formation and maintenance of sharp borders. The hindbrain is
      subdivided into a series of segments with distinct anteroposterior identity that
      underlies the specification of distinct neuronal cell types. During early stages
      of segmentation, cell identity switching contributes to the refinement of borders
      and enables homogenous territories to be maintained despite intermingling of
      cells between segments. At later stages, there is a specific restriction to cell
      intermingling between segments that is mediated by Eph receptor and ephrin
      signaling. Eph-ephrin signaling can restrict cell intermingling and sharpen
      borders through multiple mechanisms, including the regulation of cell adhesion
      and contact inhibition of cell migration.

PMID- 24014459
TI  - Synthesis of C-disaccharides through a one-pot alkynol cycloisomerization
      reductive deoxygenation.

PMID- 24014455
TI  - Initial neurogenesis in Drosophila.
AB  - Early neurogenesis comprises the phase of nervous system development during which
      neural progenitor cells are born. In early development, the embryonic ectoderm is
      subdivided by a conserved signaling mechanism into two main domains, the
      epidermal ectoderm and the neurectoderm. Subsequently, cells of the neurectoderm
      are internalized and form a cell layer of proliferating neural progenitors. In
      vertebrates, the entire neurectoderm folds into the embryo to give rise to the
      neural tube. In Drosophila and many other invertebrates, a subset of
      neurectodermal cells, called neuroblasts (NBs), delaminates and forms the neural
      primordium inside the embryo where they divide in an asymmetric, stem cell-like
      mode. The remainder of the neurectodermal cells that stay behind at the surface
      loose their neurogenic potential and later give rise to the ventral part of the
      epidermis. The genetic and molecular analysis of the mechanisms controlling
      specification and proliferation of NBs in the Drosophila embryo, which played a
      significant part in pioneering the field of modern developmental neurobiology,
      represents the topic of this review.

PMID- 24014458
TI  - Panostotic expansile bone disease with massive jaw tumor formation and a novel
      mutation in the signal peptide of RANK.
AB  - Precise regulation of bone resorption is critical for skeletal homeostasis. We
      report a 32-year-old man with a panostotic expansile bone disease and a massive
      hemorrhagic mandibular tumor. Originally from Mexico, he was deaf at birth and
      became bow-legged during childhood. There was no family history of skeletal
      disease. Puberty occurred normally, but during adolescence he experienced
      difficulty straightening his limbs, sustained multiple fractures, and developed a
      bony tumor on his chin. By age 18 years, all limbs were misshapen. The mandibular
      mass grew and protruded from the oral cavity, extending to the level of the lower
      ribs. Other bony defects included a similar maxillary mass and serpentine limbs.
      Upon referral at age 27 years, biochemical studies showed serum alkaline
      phosphatase of 1760 U/L (Nl: 29-111) and other elevated bone turnover markers.
      Radiography of the limbs showed medullary expansion and cortical thinning with
      severe bowing. Although the jaw tumors were initially deemed inoperable,
      mandibular mass excision and staged partial maxillectomy were eventually
      performed. Tumor histopathology showed curvilinear trabeculae of woven bone on a
      background of hypocellular fibrous tissue. Fibrous dysplasia of bone was
      suspected, but there was no mutation in codon 201 of GNAS in samples from blood
      or tumor. His clinical and radiographic findings, elevated serum markers, and
      disorganized bone morphology suggested amplified receptor activator of NF-kappaB
      (RANK) signaling, even though his disorder differed from conditions with known
      constitutive activation of RANK signaling (eg, familial expansile osteolysis). We
      found a unique 12-base pair duplication in the signal peptide of TNFRSF11A, the
      gene that encodes RANK. No exon or splice site mutations were found in the genes
      encoding RANK ligand or osteoprotegerin. Alendronate followed by pamidronate
      therapies substantially decreased his serum alkaline phosphatase activity. This
      unique patient expands the phenotypes and genetic basis of the mendelian
      disorders of RANK signaling activation.

PMID- 24014460
TI  - Physical activity correlates in persons with binge eating disorder: a systematic
      review.
AB  - Understanding the factors that influence physical activity in persons with binge
      eating disorders can aid the design of more effective interventions. In order to
      address this, the present paper provides a systematic quantitative review of the
      correlates of physical activity in people with binge eating disorder. We searched
      PsycINFO, PubMed and PEDro from inception until June 2013. Keywords included
      'binge eating' with 'physical activity' or 'exercise', or 'physical inactivity'
      or 'sedentary'. Nine papers involving 636 (489 women) persons with binge eating
      disorders and evaluating 24 correlates were included. No consistent physical
      activity correlates were reported in four or more studies. The only significant
      correlate with lower physical activity participation reported in more than one
      study was a negative body attitude. Further research is required to address this
      current gap in literature.

PMID- 24014462
TI  - Potential rearrangements in the reaction catalyzed by the indole
      prenyltransferase FtmPT1.
AB  - The indole prenyltransferase FtmPT1 catalyzes the C-2 normal prenylation of
      brevianamide F (cyclo-L-Trp-L-Pro) to give tryprostatin B. A previous structural
      analysis and studies with alternate substrates suggest that the reaction might
      not proceed through a direct C-2 attack, but could involve a C-3 prenylation
      followed by a rearrangement. In this work we investigated the reactivity of
      FtmPT1 with tryptophan, 5-hydroxybrevianamide, and 2-methylbrevianamide, and
      isolated products that had been reverse prenylated at C-3 and normal prenylated
      at N-1, C-3, or C-4. The formation of these products can be rationalized through
      mechanisms involving either an initial C-3 normal or C-3 reverse prenylation. In
      addition, we demonstrate that a C-3 reverse prenylated indole can undergo a
      nonenzymatic aza-Cope rearrangement at 37  degrees C to give an N-1 normal
      prenylated product. Together, these studies broaden the known product scope of
      this interesting catalyst and suggest that alternative mechanisms might be
      operating. 

PMID- 24014461
TI  - Early deprivation impairs the development of balance and bilateral coordination.
AB  - This study examined balance and bilateral coordination skills in a sample of
      internationally adopted, post-institutionalized (PI) children. We compared the
      performance of these PI children to two age-matched groups. One was a group of
      children who were internationally adopted from foster care (FC). The second group
      consisted of non-adopted children being raised in their birth families, who
      served as controls (Control). Both PI and FC children scored lower than control
      children on balance, while PI children scored lower than both FC and control
      children on bilateral coordination. These results suggest that aspects of
      institutional rearing impact the development of bilateral coordination, while
      factors common to internationally adopted children other than
      institutionalization impact the development of balance. Region of birth (Asia,
      Latin/South America, Russia/Eastern Europe) did not moderate associations between
      institutional duration and bilateral coordination.

PMID- 24014463
TI  - Identification of chiral alkenyl- and alkynylcarbinols as pharmacophores for
      potent cytotoxicity.
AB  - Illumination by acetylene: Systematic structural variations in a series of
      archetypal acetylenic lipids derived from the naturally occurring (S,E)-icos-4-en
      1-yn-3-ol allowed the discovery of a series of 3R-like 1,4-di-unsaturated
      carbinol units with a significant and systematic enantiomeric effect on
      cytotoxicity. 

PMID- 24014464
TI  - Male reproductive strategies in black and gold howler monkeys (Alouatta caraya).
AB  - Behavioral and demographic factors such as group size, social structure,
      dispersal patterns, and mating systems affect male reproductive success. In the
      present study, we analyze the relationship between social structure, genetic
      relatedness of adult males and offspring paternity in one population of Alouatta
      caraya inhabiting a continuous forest in Northern Argentina. After 14 months of
      behavioral studies and genotyping 11 microsatellites, we found that dominant or
      central males achieved greater mating success and fathered all the offspring
      conceived during our study in two multimale-multifemale groups (both including
      three adult males). Although skewed toward the dominant males, females copulated
      with almost all resident males and with extra group males. We found significantly
      fewer agonistic interactions between adult males in the group with fewer females
      and where males were more genetically related to each other (average relatedness
      r = 0.237; 0.015 int/ind/hr vs. r = 0.02; 0.029 int/ind/hr). Paternity was also
      analyzed in two other neighboring groups which also showed strong skew to one
      male over a 2-year period. These results reveal that even though female black and
      gold howlers mate with many males, infants are typically fathered by one dominant
      male.

PMID- 24014465
TI  - Gray TiO2 nanowires synthesized by aluminum-mediated reduction and their
      excellent photocatalytic activity for water cleaning.
AB  - Not always black and white: Gray TiO2 nanowires with high photocatalytic activity
      have been successfully synthesized by aluminum-mediated reduction in a two-zone
      furnace. These wires, which possess a core (TiO(2-x))/shell (TiO2 ) structure,
      exhibit visible-light and even IR absorption with high photocatalytic activity,
      far exceeding that of commercial Degussa P25. They show high stability in air and
      water under solar-light irradiation.

PMID- 24014466
TI  - The golden hour of stroke intervention: effect of thrombectomy procedural time in
      acute ischemic stroke on outcome.
AB  - INTRODUCTION: Outcome studies in acute ischemic stroke (AIS) have focused on time
      from symptom onset to treatment. The purpose of this study was to investigate
      whether time to achieve vessel recanalization from groin puncture affects
      outcomes. METHODS: We studied all AIS cases that underwent intra-arterial therapy
      between May 2008 and October 2012 at a high volume center for anterior
      circulation occlusions. Candidacy for thrombectomy is determined by CT perfusion
      imaging, irrespective of time of onset. Patients were then dichotomized into two
      groups: 'Early recan' assigned in which recanalization was achieved in <=60 min
      from groin puncture and 'Delayed recan' in which procedures extended beyond 60
      min. Time to recanalize was also studied as a continuous variable. RESULTS: 159
      patients (53.5% women, mean age 66.4+/-15.2 years) were identified. The mean
      National Institutes of Health Stroke Scale (NIHSS) score was similar between
      'Early recan' patients (16.8+/-6.1) compared with 'Delayed recan' patients
      (15.4+/-5.8, p=0.149). Among the 'Early recan' patients, recanalization was
      achieved in 40.7+/-13.6 min compared with 101.7+/-32.5 min in the 'Delayed recan'
      patients (p<0.0001). The likelihood of achieving a good outcome (modified Rankin
      Scale score 0-2) was higher in the 'Early recan' group (53.6%) compared with the
      'Late recan' group (30.8%; p=0.009). On logistic regression analysis, time to
      recanalization from groin puncture, baseline NIHSS, revascularization, diabetes,
      and hemorrhages were found to significantly impact on outcome at 90 days, as
      measured by the modified Rankin Scale. CONCLUSIONS: Our findings suggest that
      extending mechanical thrombectomy procedure times beyond 60 min increases
      complications and device cost rates while worsening outcomes. These findings can
      serve as a time frame of when it is prudent to abort a failed thrombectomy case.

PMID- 24014467
TI  - Carotid artery stenting without post-stenting balloon dilatation.
AB  - PURPOSE: To evaluate the clinical outcome and MRI findings after carotid artery
      stenting (CAS) without post-dilatation. METHODS: Between May 2005 and April 2012,
      a total of 169 consecutive patients (61.4% symptomatic) underwent 176 CAS
      procedures performed with an embolic protection device (GuardWire, n=116;
      FilterWire EZ, n=60). All stents were deployed without post-dilatation.
      Periprocedural complications and mid-term outcomes were analyzed. RESULTS: The
      stroke rate was 2.3% within 30 days post-CAS (asymptomatic patients 1.5%;
      symptomatic patients 2.8%). Cerebral infarction occurred in one asymptomatic
      patient (1.5%) and one symptomatic patient (0.9%). Intracranial hemorrhage
      occurred in two symptomatic patients (1.9%). Post-CAS diffusion-weighted imaging
      (DWI) revealed a high-intensity area in 26 of 176 procedures (14.8%). Ipsilateral
      stroke after 31 days occurred in two patients (1.1%) and restenosis occurred in
      six (3.4%). A post-CAS comparison of the embolic protection devices revealed no
      difference in stroke incidence within 30 days and in DWI high-intensity area.
      CONCLUSIONS: Our CAS procedure without post-dilatation is feasible, safe and
      associated with a low incidence of stroke and restenosis.

PMID- 24014468
TI  - Flexible tip guides and intermediate catheters: two center experience and a
      proposed taxonomy.
AB  - BACKGROUND: Stable access to target lesions is foundational to endovascular
      therapy, be it in hemorrhagic or ischemic disease. Continued evolution in access
      technology has resulted in next generation catheters that afford improved
      trackability and proximal support. OBJECTIVE: Assess safety and patterns of use
      at two high volume centers, and conceptualize usage patterns. MATERIALS AND
      METHODS: A retrospective review of 608 cases in which a 'next generation'
      catheter was used during 2008-2010 at Cleveland Clinic (Cleveland, Ohio, USA) and
      throughout 2009-2010 at Emory University Hospital (Atlanta, Georgia, USA) was
      conducted, and the cases classified by indication. Catheter placement, distal
      most location, and related complications were recorded and experience summarized.
      We also reviewed the differences in the catheters and the rationale for catheter
      selection, as well as relative costs for each approach. RESULTS: 311 Neuron 053,
      166 Neuron 070, 36 distal access catheter (DAC) 3.9 F, 61 DAC 4.3 F, and 34 DAC
      5.2 F catheters were deployed. Of these, 459 placements were in the anterior
      circulation, 130 in the posterior circulation, 11 in the external carotid artery,
      and eight were used intravenously. Complication rates were 9/131 (6.9%) for the
      DAC catheter group, 16/311 (5.1%) for the Neuron 053 group, and 14/166 (8.4%) for
      the Neuron 070 group (p=0.37, chi(2) test). CONCLUSIONS: Next generation access
      catheters possess characteristics that blend qualities of traditional
      microcatheters and stiff guide catheters. There was no statistically significant
      difference in complication rates between the various catheter families in this
      small retrospective review, and the complication rates were similar to historical
      complication rates.

PMID- 24014469
TI  - Mechanical endovascular procedure for the treatment of acute ischemic stroke
      caused by total detachment of a papillary fibroelastoma.
AB  - Papillary fibroelastomas (PFEs) are rare cardiac tumors. Despite their benign
      nature, they are associated with a high risk of embolic complications including
      stroke. Endovascular treatment has been reported as a safe procedure in patients
      with myxoma, the most common type of primary cardiac tumor. A case of ischemic
      stroke due to embolization of a PFE successfully treated with a single pass of a
      retrievable stent is described. A 64-year-old patient with a right middle
      cerebral artery syndrome was treated with an intravenous and endovascular
      protocol as a revascularization procedure. Mechanical thrombectomy resulted in
      total recanalization with clinical improvement. Histological examination of the
      clot showed pathological features of a typical PFE. The endovascular treatment
      was safe and effective. With mechanical embolectomy it is possible to obtain and
      analyze pathological specimens, enabling the diagnosis of uncommon strokes. 

PMID- 24014470
TI  - Pregnancy-associated osteoporosis with a heterozygous deactivating LDL receptor
      related protein 5 (LRP5) mutation and a homozygous methylenetetrahydrofolate
      reductase (MTHFR) polymorphism.
AB  - Pregnancy-associated osteoporosis (PAO) is a rare, idiopathic disorder that
      usually presents with vertebral compression fractures (VCFs) within 6 months of a
      first pregnancy and delivery. Spontaneous improvement is typical. There is no
      known genetic basis for PAO. A 26-year-old primagravida with a neonatal history
      of unilateral blindness attributable to hyperplastic primary vitreous sustained
      postpartum VCFs consistent with PAO. Her low bone mineral density (BMD) seemed to
      respond to vitamin D and calcium therapy, with no fractures after her next
      successful pregnancy. Investigation of subsequent fetal losses revealed
      homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T
      polymorphism associated both with fetal loss and with osteoporosis (OP). Because
      her neonatal unilateral blindness and OP were suggestive of loss-of-function
      mutation(s) in the gene that encodes LDL receptor-related protein 5 (LRP5), LRP5
      exon and splice site sequencing was also performed. This revealed a unique
      heterozygous 12-bp deletion in exon 21 (c.4454_4465del, p.1485_1488del SSSS) in
      the patient, her mother and sons, but not her father or brother. Her mother had a
      normal BMD, no history of fractures, PAO, ophthalmopathy, or fetal loss. Her two
      sons had no ophthalmopathy and no skeletal issues. Her osteoporotic father (with
      a family history of blindness) and brother had low BMDs first documented at ages
      ~40 and 32 years, respectively. Serum biochemical and bone turnover studies were
      unremarkable in all subjects. We postulate that our patient's heterozygous LRP5
      mutation together with her homozygous MTHFR polymorphism likely predisposed her
      to low peak BMD. However, OP did not cosegregate in her family with the LRP5
      mutation, the homozygous MTHFR polymorphism, or even the combination of the two,
      implicating additional genetic or nongenetic factors in her PAO. Nevertheless,
      exploration for potential genetic contributions to PAO may explain part of the
      pathogenesis of this enigmatic disorder and identify some at-risk women.

PMID- 24014472
TI  - Syntheses and anti-tubercular activity of beta-substituted and alpha,beta
      disubstituted peptidyl beta-aminoboronates and boronic acids.
AB  - Tuberculosis is still affecting millions of people worldwide, and new resistant
      strains of Mycobacterium tuberculosis are being found. It is therefore necessary
      to find new compounds for treatment. In this paper, we report the synthesis and
      in vitro testing of peptidyl beta-aminoboronic acids and beta-aminoboronates with
      anti-tubercular activity.

PMID- 24014473
TI  - Characterization of endocytic uptake of MK2-inhibitor peptides.
AB  - Cell penetrating peptides (CPP) have been widely used to increase the cellular
      delivery of their associated cargo. Multiple modes of uptake have been
      identified; however, they cannot be predicted a priori. Elucidating these
      mechanisms is important for understanding peptide function as well as further
      optimizing cellular delivery. We have developed a class of mitogen activated
      protein kinase activated protein kinase 2 (MK2) inhibitor peptides, named FAK and
      YARA that utilize CPP domains to gain cellular access. In this study, we
      investigate the mechanism of endocytosis of these MK2 inhibitors by examining the
      uptake of fluorescently labeled peptide in human monocyte (THP-1) and mesothelial
      cells, and looking for colocalization with known markers of endocytosis. Our
      results indicate that uptake of the MK2 inhibitors was minimally enhanced by the
      addition of the fluorescent label, and that the type of endocytosis used by the
      inhibitor depends on several factors including concentration, cell type, and
      which CPP was used. We found that in THP-1 cells, the uptake of YARA occurred
      primarily via macropinocytosis, whereas FAK entered via all three mechanisms of
      endocytosis examined in this study. In mesothelial cells, uptake of YARA occurred
      via caveolae-mediated endocytosis, but became less specific at higher
      concentrations; whereas uptake of FAK occurred through clathrin-mediated
      endocytosis. In all cases, the delivery resulted in active inhibition of MK2. In
      summary, the results support endocytic uptake of fluorescently labeled FAK and
      YARA in two different cell lines, with the mechanism of uptake dependent on
      extracellular concentration, cell type, and choice of CPP.

PMID- 24014474
TI  - Enhanced binding to and killing of hepatocellular carcinoma cells in vitro by
      melittin when linked with a novel targeting peptide screened from phage display.
AB  - A random phage 12-mer peptide library and a whole-cell subtractive biopanning
      protocol against HepG2 cells were used to select a novel peptide-specific binding
      to hepatocellular carcinoma cells. As a result, peptide SLSLITMLKISR (AM-2) was
      screened as a novel homing peptide to hepatocellular carcinoma cells, tested by
      immunofluorescence and immunochemistry assays. Subsequently, peptide AM-2 was
      linked to melittin by A(EAAAK)2A, and the antitumor effect of this ligation
      product was detected by MTT assay, fluorescence-activated cell sorting, and
      scanning electron microscopy methods. Results of cell growth inhibition tests
      confirmed that the affinity of melittin was increased after being incorporated
      into AM-2, and AM-2-melittin specifically targeted and killed HepG2 cells in
      vitro. Thus, AM-2 is a valuable ligand for tumor targeting, which leads to
      increased binding and killing effect of hepatocellular carcinoma cells in vitro
      when ligated to melittin, and AM-2-melittin has a clinical potential application
      as target agents for the treatment of human hepatocellular carcinoma.

PMID- 24014475
TI  - Identification of small peptides inhibiting the integrase-LEDGF/p75 interaction
      through targeting the cellular co-factor.
AB  - The integration of the viral DNA into the host genome is one of the essential
      steps in the HIV replication cycle. This process is mediated by the viral enzyme
      integrase (IN) and lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75
      has been identified as a crucial cellular co-factor of integration that acts by
      tethering IN to the cellular chromatin. Recently, circular peptides were
      identified that bind to the C-terminal domain of IN and disrupt the interaction
      with LEDGF/p75. Starting from the circular peptides, we identified a short
      peptidic sequence able to inhibit the LEDGF/p75-IN interaction at low MUM
      concentration through its binding to the IN binding site of LEDGF/p75. This
      discovery can lead to the synthesis of peptidomimetics with high anti-HIV
      activity targeting the cellular co-factor LEDGF/p75 and not the viral protein IN.

PMID- 24014476
TI  - Shape-controlled nanostructures in heterogeneous catalysis.
AB  - Nanotechnologies have provided new methods for the preparation of nanomaterials
      with well-defined sizes and shapes, and many of those procedures have been
      recently implemented for applications in heterogeneous catalysis. The control of
      nanoparticle shape in particular offers the promise of a better definition of
      catalytic activity and selectivity through the optimization of the structure of
      the catalytic active site. This extension of new nanoparticle synthetic
      procedures to catalysis is in its early stages, but has shown some promising
      leads already. Here, we survey the major issues associated with this
      nanotechnology-catalysis synergy. First, we discuss new possibilities associated
      with distinguishing between the effects originating from nanoparticle size versus
      those originating from nanoparticle shape. Next, we survey the information
      available to date on the use of well-shaped metal and non-metal nanoparticles as
      active phases to control the surface atom ensembles that define the catalytic
      site in different catalytic applications. We follow with a brief review of the
      use of well-defined porous materials for the control of the shape of the space
      around that catalytic site. A specific example is provided to illustrate how new
      selective catalysts based on shape-defined nanoparticles can be designed from
      first principles by using fundamental mechanistic information on the reaction of
      interest obtained from surface-science experiments and quantum-mechanics
      calculations. Finally, we conclude with some thoughts on the state of the field
      in terms of the advances already made, the future potentials, and the possible
      limitations to be overcome.

PMID- 24014477
TI  - Analytic versus systemic group therapy for women with a history of child sexual
      abuse: 1-year follow-up of a randomized controlled trial.
AB  - OBJECTIVE: This randomized prospective study examines durability of improvement
      in general symptomatology, psychosocial functioning and interpersonal problems,
      and compares the long-term efficacy of analytic and systemic group psychotherapy
      in women 1 year after completion of treatment for childhood sexual abuse. DESIGN
      AND METHODS: Women (n = 106) randomly assigned to analytic or systemic
      psychotherapy completed the Symptom Checklist-90-R, Global Assessment of
      Functioning, Global Life Quality, Registration Chart Questionnaire, and Flashback
      Registration at pre-treatment, post-treatment, and at a 1-year follow-up.
      RESULTS: Post-treatment gains were significant for both treatment modalities on
      all measures, but significantly larger after systemic therapy. Significant
      treatment response was maintained 1-year post-treatment, but different
      trajectories were observed: 1 year after treatment completion, improvements for
      analytic therapy were maintained, whereas they decreased after systemic therapy,
      resulting in no statistically significant difference in gains between the groups
      at the 1-year follow-up. Despite maintaining significant gains, more than half of
      the patients remained above cut-off for caseness concerning general
      symptomatology at post-treatment and at 1-year follow-up. CONCLUSION: The
      findings stress the importance of long-term follow-up data in effect studies.
      Different trajectories were associated with the two treatments, but improvement
      in the two treatment groups did not differ significantly at the 1-year follow-up.
      Implications of the difference in trajectories for treatment planning are
      discussed. PRACTITIONER POINTS: Both analytic and systemic group therapy proved
      efficient in improving general symptomatology, psychosocial functioning, and
      interpersonal problems in women with a history of CSA and gains were maintained
      at a 1-year follow-up. Despite maintaining statistically significant gains at the
      1-year follow-up, 54% of the patients remained above the cut-off for caseness
      with respect to general symptomatology, which may indicate a need for further
      treatment. Different pre-post follow-up treatment trajectories were observed
      between the two treatment modalities. Thus, while systemic group therapy showed a
      significantly better outcome immediately after termination, gains in the systemic
      treatment group decreased during follow-up, while gains were maintained during
      follow-up in analytic group therapy.

PMID- 24014478
TI  - Improved synthesis of capuramycin and its analogues.
AB  - Capuramycin and its congeners are considered to be important lead molecules for
      the development of a new drug for multidrug-resistant (MDR) Mycobacterium
      tuberculosis infections. Extensive structure-activity relationship studies of
      capuramycin to improve the efficacy have been limited because of difficulties in
      selectively chemically modifying the desired position(s) of the natural product
      with biologically interesting functional groups. We have developed efficient
      syntheses of capuramycin and its analogues by using new protecting groups,
      derived from the chiral (chloro-4-methoxyphenyl)(chlorophenyl)methanols, for the
      uridine ureido nitrogen and primary alcohol. The chiral nonracemic (2,6-dichloro
      4-methoxyphenyl)(2,4-dichlorophenyl)methanol derivative is a useful reagent to
      resolve rac-3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, the (S)
      configuration isomer of which plays a significant role in improving the
      mycobactericidal activity of capuramycin. 

PMID- 24014479
TI  - Hedonic hunger and binge eating among women with eating disorders.
AB  - BACKGROUND: Hedonic hunger, the appetitive drive to eat to obtain pleasure in the
      absence of an energy deficit, is associated with overeating and with loss of
      control over eating, but has not been investigated among individuals with eating
      disorders. OBJECTIVE: (1) to compare participants with anorexia nervosa,
      restricting type (AN-R), anorexia nervosa, binge-purge type (AN-B/P), and bulimia
      nervosa (BN) on scores on the Power of Food Scale (PFS), a self-report measure of
      hedonic hunger; (2) to examine the relation between PFS scores and frequency of
      binge eating; and (3) to examine whether pre-treatment PFS scores predict weight
      change during treatment. METHOD: The PFS and measures of eating disorder
      symptomatology were administered to female patients with AN (N = 119) and BN (N =
      144) at admission to residential treatment. RESULTS: Participants with BN scored
      higher on the PFS compared to participants with AN-R or AN-B/P; there was a trend
      for those with AN-B/P to score higher than those with AN-R. PFS scores were
      positively associated with binge eating frequency among participants with BN;
      these associations remained significant when controlling for restraint and weight
      suppression. A similar pattern was found among participants with AN. PFS scores
      predicted weight change in AN but not BN. DISCUSSION: Results suggest that
      hedonic processes may be important in stimulating binge eating. Furthermore,
      hedonic appetite may facilitate weight restoration in AN. Further research should
      investigate whether pre-treatment PFS scores have prognostic significance with
      respect to eating disorder symptoms.

PMID- 24014480
TI  - Physiological functions of osteoblast lineage and T cell-derived RANKL in bone
      homeostasis.
AB  - The cytokine RANKL is essential for osteoclast development in bone. The cellular
      sources of RANKL for support of osteoclast generation under various
      pathophysiological conditions have remained unclear, however. Here we show that
      inactivation of Rankl specifically in osteoblast lineage cells of mice with the
      use of an Osterix-Cre transgene results in typical osteopetrosis in the
      trabecular compartment of the tibia, with the phenotype being progressively less
      marked in the femur and vertebrae. In contrast to its effects on trabecular bone,
      RANKL deficiency in osteoblast lineage resulted in thinning of the femoral cortex
      in association with suppression of bone formation during the modeling process.
      Ablation of RANKL specifically in T cells resulted in a moderate but significant
      increase in tibial trabecular bone. Mice with RANKL deficiency in osteoblast
      lineage were protected from bone loss induced by ovariectomy as well as from
      joint destruction associated with arthritis, whereas loss of RANKL in T cells did
      not confer such protection. Finally, inducible deletion of Rankl selectively in
      the osteoblasts from 6 to 12 weeks of age resulted in an increase in bone mass in
      association with reduced bone resorption and formation. Our results thus suggest
      that RANKL produced by osteoblasts contributes to osteoclast development in vivo.

PMID- 24014481
TI  - "I think this is maybe our Achilles heel..." exploring GPs' responses to young
      people presenting with emotional distress in general practice: a qualitative
      study.
AB  - OBJECTIVE: An exploratory study to investigate general practitioners' (GPs')
      views and experiences of consulting with young people (aged 12-19 years)
      presenting with emotional distress in general practice. DESIGN: A qualitative
      study using grounded theory and situational analysis. Empirical data were
      generated through in-depth interviews based on a topic guide developed from the
      literature, and augmented with a series of situational maps. Continuous field
      notes and theoretical memos were recorded during data collection and analysis.
      The data were analysed using the constant comparative method of grounded theory.
      There were three levels of analysis. The first level developed the open codes and
      is presented here. SETTING: 18 general practices located in the north east of
      England. The practices recruited included rural, urban and mixed populations of
      patients who were predominantly living in socioeconomically disadvantaged
      communities. PARTICIPANTS: 19 GPs (10 women) aged between 29 and 59 years
      participated. The modal age range was 40-49 years. Theoretical sampling was used
      to guide recruitment and continued until theoretical saturation was reached.
      RESULTS: The overarching finding was that anxiety about practice dominated
      clinical consultations involving young people presenting with emotional distress.
      GPs responded differently to anxiety and to related uncertainties about
      professional practice, independent of GP age or gender. Anxiety occurred in the
      consultation, at an external level, across disciplinary boundaries, in relation
      to communication with young people and secondary to the complexity of
      presentations. CONCLUSIONS: Adolescent emotional distress presents professional
      challenges to GPs who feel ill-equipped and inadequately prepared to address
      early need. Medical education needs to prepare doctors better. More research is
      needed to look at what factors facilitate or prohibit greater GP engagement with
      emotionally distressed young people.

PMID- 24014482
TI  - Effects of telephone health mentoring in community-recruited chronic obstructive
      pulmonary disease on self-management capacity, quality of life and psychological
      morbidity: a randomised controlled trial.
AB  - OBJECTIVES: To assess benefits of telephone-delivered health mentoring in
      community-based chronic obstructive pulmonary disease (COPD). DESIGN: Cluster
      randomised controlled trial. SETTING: Tasmanian general practices: capital city
      (11), large rural (3), medium rural (1) and small rural (16). PARTICIPANTS:
      Patients were invited (1207) from general practitioner (GP) databases with COPD
      diagnosis and/or tiotropium prescription, response rate 49% (586), refused (176)
      and excluded (criteria: smoking history or previous study, 68). Spirometry
      testing (342) confirmed moderate or severe COPD in 182 (53%) patients.
      RANDOMISATION: By random numbers code, block stratified on location, allocation
      by sequentially numbered, opaque and sealed envelopes. INTERVENTION: Health
      mentor (HM) group received regular calls to manage illness issues and health
      behaviours from trained community health nurses using negotiated goal setting:
      problem solving, decision-making and action planning. CONTROL: usual care (UC)
      group received GP care plus non-interventional brief phone calls. OUTCOMES:
      Measured at 0, 6 and 12 months, the Short Form 36 (SF-36) and St George's
      Respiratory Questionnaire (SGRQ, primary); Partners In Health (PIH) Scale for
      self-management capacity, Hospital Anxiety and Depression Scale (HADS), Center
      for Epidemiologic Studies-Depression (CES-D) questionnaire, Post-Traumatic Stress
      Disorder Checklist, Satisfaction with life and hospital admissions (secondary).
      RESULTS: 182 participants with COPD (age 68+/-8 years, 62% moderate COPD and 53%
      men) were randomised (HM=90 and UC=92). Mixed model regression analysis
      accounting for clustering, adjusting for age, gender, smoking status and airflow
      limitation assessed efficacy (regression coefficient, beta, reported per 6-month
      visit). There was no difference in quality of life between groups, but self
      management capacity increased in the HM group (PIH overall 0.15, 95% CI 0.03 to
      0.29; knowledge domain 0.25, 95% CI 0.00 to 0.50). Anxiety decreased in both
      groups (HADS A 0.35; 95% CI -0.65 to -0.04) and coping capacity improved (PIH
      coping 0.15; 95% CI 0.04 to 0.26). CONCLUSIONS: Health mentoring improved self
      management capacity but not quality of life compared to regular phone contact,
      which itself had positive effects where decline is generally expected.

PMID- 24014483
TI  - The work of commissioning: a multisite case study of healthcare commissioning in
      England's NHS.
AB  - OBJECTIVE: To examine the work of commissioning care for people with long-term
      conditions and the factors inhibiting or facilitating commissioners making
      service change. DESIGN: Multisite mixed methods case study research, combining
      qualitative analysis of interviews, documents and observation of meetings.
      PARTICIPANTS: Primary care trust managers and clinicians, general practice-based
      commissioners, National Health Service trust and foundation trust senior managers
      and clinicians, voluntary sector and local government representatives. SETTING:
      Three 'commissioning communities' (areas covered by a primary care trust) in
      England, 2010-2012. RESULTS: Commissioning services for people with long-term
      conditions was a long drawn-out process involving a range of activities and
      partners. Only some of the activities undertaken by commissioners, such as
      assessment of local health needs, coordination of healthcare planning and service
      specification, appeared in the official 'commissioning cycle' promoted by the
      Department of Health. Commissioners undertook a significant range of additional
      activities focused on reviewing and redesigning services and providing support
      for implementation of new services. These activities often involved partnership
      working with providers and other stakeholders and appeared to be largely divorced
      from contracting and financial negotiations. At least for long-term condition
      services, the time and effort involved in such work appeared to be
      disproportionate to the anticipated or likely service gains. Commissioners
      adopting an incremental approach to service change in defined and manageable
      areas of work appeared to be more successful in terms of delivering planned
      changes in service delivery than those attempting to bring about wide-scale
      change across complex systems. CONCLUSIONS: Commissioning for long-term condition
      services challenges the conventional distinction between commissioners and
      providers with a significant amount of work focused on redesigning services in
      partnership with providers. Such work is labour-intensive and potentially
      unsustainable at a time of reduced finances. New clinical commissioning groups
      will need to determine how best to balance the relational and transactional
      elements of commissioning.

PMID- 24014484
TI  - Education influences the association between genetic variants and refractive
      error: a meta-analysis of five Singapore studies.
AB  - Refractive error is a complex ocular trait governed by both genetic and
      environmental factors and possibly their interplay. Thus far, data on the
      interaction between genetic variants and environmental risk factors for
      refractive errors are largely lacking. By using findings from recent genome-wide
      association studies, we investigated whether the main environmental factor,
      education, modifies the effect of 40 single nucleotide polymorphisms on
      refractive error among 8461 adults from five studies including ethnic Chinese,
      Malay and Indian residents of Singapore. Three genetic loci SHISA6-DNAH9, GJD2
      and ZMAT4-SFRP1 exhibited a strong association with myopic refractive error in
      individuals with higher secondary or university education (SHISA6-DNAH9:
      rs2969180 A allele, beta = -0.33 D, P = 3.6 * 10(-6); GJD2: rs524952 A allele,
      beta = -0.31 D, P = 1.68 * 10(-5); ZMAT4-SFRP1: rs2137277 A allele, beta = -0.47
      D, P = 1.68 * 10(-4)), whereas the association at these loci was non-significant
      or of borderline significance in those with lower secondary education or below (P
      for interaction: 3.82 * 10(-3)-4.78 * 10(-4)). The evidence for interaction was
      strengthened when combining the genetic effects of these three loci (P for
      interaction = 4.40 * 10(-8)), and significant interactions with education were
      also observed for axial length and myopia. Our study shows that low level of
      education may attenuate the effect of risk alleles on myopia. These findings
      further underline the role of gene-environment interactions in the
      pathophysiology of myopia.

PMID- 24014486
TI  - Passing the torch.

PMID- 24014485
TI  - Epigenetics meets metabolomics: an epigenome-wide association study with blood
      serum metabolic traits.
AB  - Previously, we reported strong influences of genetic variants on metabolic
      phenotypes, some of them with clinical relevance. Here, we hypothesize that DNA
      methylation may have an important and potentially independent effect on human
      metabolism. To test this hypothesis, we conducted what is to the best of our
      knowledge the first epigenome-wide association study (EWAS) between DNA
      methylation and metabolic traits (metabotypes) in human blood. We assess 649
      blood metabolic traits from 1814 participants of the Kooperative
      Gesundheitsforschung in der Region Augsburg (KORA) population study for
      association with methylation of 457 004 CpG sites, determined on the Infinium
      HumanMethylation450 BeadChip platform. Using the EWAS approach, we identified two
      types of methylome-metabotype associations. One type is driven by an underlying
      genetic effect; the other type is independent of genetic variation and
      potentially driven by common environmental and life-style-dependent factors. We
      report eight CpG loci at genome-wide significance that have a genetic variant as
      confounder (P = 3.9 * 10(-20) to 2.0 * 10(-108), r(2) = 0.036 to 0.221). Seven
      loci display CpG site-specific associations to metabotypes, but do not exhibit
      any underlying genetic signals (P = 9.2 * 10(-14) to 2.7 * 10(-27), r(2) = 0.008
      to 0.107). We further identify several groups of CpG loci that associate with a
      same metabotype, such as 4-vinylphenol sulfate and 4-androsten-3-beta,17-beta
      diol disulfate. In these cases, the association between CpG-methylation and
      metabotype is likely the result of a common external environmental factor,
      including smoking. Our study shows that analysis of EWAS with large numbers of
      metabolic traits in large population cohorts are, in principle, feasible. Taken
      together, our data suggest that DNA methylation plays an important role in
      regulating human metabolism.

PMID- 24014487
TI  - Palliative care nursing interventions in Thailand.
AB  - PURPOSE: This study aimed to describe the nursing interventions that nurses in
      Thailand identify as most important in promoting dignified dying. DESIGN: This
      study used a cross-sectional descriptive design. METHOD: A total of 247 Thai
      nurses completed a paper-and-pencil survey written in Thai. The survey included
      both demographic questions and palliative care interventions, listed with
      summative rating scales, from the International Classification for Nursing
      Practice (ICNP) catalogue Palliative Care for Dignified Dying. Descriptive
      statistics were used to analyze the data. FINDINGS: The five most important
      nursing interventions to promote dignified dying, ranked by average importance
      rating, were (a) maintain dignity and privacy, (b) establish trust, (c) manage
      pain, (d) establish rapport, and (e) manage dyspnea. CONCLUSIONS: This research
      identified the palliative care nursing interventions considered most important by
      nurses in Thailand to promote dignified dying. IMPLICATIONS: The ICNP catalogue
      Palliative Care for Dignified Dying can be used for planning and managing
      palliative nursing care in Thailand.

PMID- 24014488
TI  - Cultural meanings of musculoskeletal diseases in Chile's Mapuche Population.
AB  - INTRODUCTION: Eight out of 10 Mapuche indigenous women have a musculoskeletal
      disorder (MSD) and do not seek early medical aid. PURPOSE: To study both the
      cultural meanings and implications of MSD from the Mapuche worldview. DESIGN:
      Ethnographic study carried out from 2008 to 2011 on indigenous reserves in
      southern Chile. Sixty-four Mapuches participated in comprehensive interviews,
      which were transcribed and analyzed by the research team. FINDINGS: Five cultural
      domains: (a) foro kutran/bone disease is the general denomination of MSD; (b) Re
      Rume Kutran/progressive and incurable course, refers to the course of the
      disease; (c) Kalul fucha mawiza/body is an old tree, describes internal
      manifestations such as worn bones, dry body, weak blood, and spiritual weakness;
      (d) witrur tripai foro/deformation is the external manifestation of MSD; and (e)
      Renma ka lof kutran/family and community suffering refers to the impact of MSD.
      CONCLUSIONS: The explanation of MSD is consistent with the integrated body-nature
      spirit worldview of the Mapuche. PRACTICE IMPLICATIONS: To provide cultural
      nursing health care so that patients receive prompt diagnosis and care.

PMID- 24014489
TI  - Moving toward greater diversity: a review of interventions to increase diversity
      in nursing education.
AB  - PURPOSE: To report the results of a comprehensive review of interventions used by
      nursing programs to increase the success of underrepresented minority nursing
      students graduating from prelicensure programs. DESIGN: This review used the five
      stages of review methodology described but Whittemore and Knafl to extract data,
      summarize, and synthesize findings of 11 studies included in this review.
      Intervention strategies were organized using concepts of Jeffreys's Nursing
      Undergraduate Retention and Success model. FINDINGS: Interventions were designed
      to improve recruitment, retention, and academic performance through a variety of
      innovative activities. CONCLUSIONS: This review highlighted the necessity for
      future researchers to report in-depth and detailed information about the
      implementation of interventions. Comprehensive information about the program,
      faculty, setting, interventions, and challenges faced during implementation were
      often missing from these reports, making replication difficult.

PMID- 24014490
TI  - A program to enhance recruitment and retention of disadvantaged and ethnically
      diverse baccalaureate nursing students.
AB  - PURPOSE: To describe and evaluate the use of a "Success in Learning:
      Individualized Pathways Program (SLIPP)" to retain and graduate disadvantaged and
      ethnically diverse nursing students. DESIGN: A summative evaluative design was
      used with a population of 77 disadvantaged and ethnically diverse students who
      were accepted into a pre-entrance preparation quarter. The program based on an
      academic success model, included six pre-entrance classes, academic, social, and
      financial support, and seven faculty development workshops. Program outcomes were
      studied using student records, survey results, and interviews. RESULTS: Following
      the pre-entrance quarter, all 77 students were accepted into the baccalaureate
      nursing program, 90.9% graduated with either a Bachelor in Science (75.3%) or
      Associate in Science (15.6%), and 98.6% of the graduates passed the state board
      registered nursing examination. DISCUSSION: Outcomes are discussed in light of
      similar programs. CONCLUSIONS: Underprepared disadvantaged and ethnically diverse
      students can successfully become registered nurses. IMPLICATIONS: Educators and
      recruiters for nursing practice should accept/hire culturally diverse
      students/nurses to expand the ethnic diversity of the nursing workforce to meet
      the needs of culturally diverse clients. Research is needed to determine the
      classes/components and length of the pre-entrance preparation program to
      successfully enhance success.

PMID- 24014491
TI  - Cross-cultural comparison of attitudes and preferences for care of the elderly
      among Australian and Chinese nursing students.
AB  - PURPOSE: The aim of this study was to compare Australian and Chinese nursing
      students' attitudes and intentions to care for the elderly and the factors
      affecting these intentions. METHOD: A cross-sectional design employed two
      questionnaires to survey 256 Australian nursing students and 204 Chinese nursing
      students within the first weeks of their nursing curriculum.Factor analysis and
      logistical regression analysis were performed to identify predictors of intent to
      care for the elderly. RESULTS: The percentage of students more likely to care for
      the elderly was significantly higher among the Chinese group (72.1%) than the
      Australian group (45.3%). Work experience with older people and being under the
      age of 20 were found to be positive predictors, whereas factors such as prejudice
      toward the elderly and beliefs that elders should live in separate housing were
      negatively associated with an intention to care for the elderly. CONCLUSIONS: The
      collectivist culture has a more positive influence on nursing students' attitudes
      toward the elderly compared with the individualist culture. IMPLICATIONS: It is
      highly recommended that elderly care settings should be incorporated in clinical
      placements and further research is needed to explore how clinical experience
      affects students' career choice.

PMID- 24014493
TI  - Transcultural nursing scholars' corner: emerging scholars.

PMID- 24014494
TI  - President's message: let's get the message out.

PMID- 24014496
TI  - Molar-ratio-dependent supramolecular isomerism: Ag(I) coordination polymers with
      bis(cyanobenzyl)sulfides.
AB  - The ratio is the key: On varying the molar ratio of the reactants, AgNO3 and
      tridentate m-L ligand, supramolecular isomers 1 and 2 comprising a 2D polymeric
      network were obtained. Conformational differences of m-L play a crucial role in
      the 2D network structures adopted for isomers 1 and 2. 

PMID- 24014495
TI  - Interleukin-1 receptor antagonist gene polymorphism and hepcidin in rheumatoid
      arthritis: Correlations with clinical and laboratory indices of disease activity.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is manifested
      as an inflammatory polyarthritis. Authors aimed to analyze the relationship
      between serum hepcidin, 25 amino acid protein, concentration and the anemia
      profiles of RA and to estimate whether it could reflect the disease activity of
      RA. Also, this study was conducted to explore the linkage between interleukin-1
      (IL-1) receptor antagonist gene (IL-1RN) polymorphism, proinflammatory cytokine,
      and RA. One hundred and eighty five RA patients were enrolled in the study. For
      all, the following criteria were measured: RA disease activities, anemia
      profiles, serum concentration of hepcidin using enzyme-linked immunosorbent
      assay, and DNA samples were used to study genotypes of IL-1RN gene by polymerase
      chain reaction. Mean concentration of serum pro-hepcidin was (93.6 +/- 31.5
      ng/mL) in 185 RA patients. An increased frequency of the IL-1RN*1 and IL-1RN*2
      alleles was relative to active RA (DAS28 > 5.1) than those with inactive to
      moderate RA (DAS28 <= 5.1). Both hepcidin and IL-1RN gene showed significant
      correlation with each other as well with RA disease activity parameters and
      anemia profile. IL-1RN gene was significantly correlated with laboratory anemia
      profile apart from transferritin. There was a significant difference among pro
      hepcidin concentration and IL-1RN frequency regarding patients with anemia of
      chronic disease and those without. In conclusion, both serum concentration of pro
      hepcidin and IL-1RN genotypes frequency reflect the disease activity, regardless
      of the anemia states in RA patients, thus they may be another potential markers
      for disease activity of RA.

PMID- 24014498
TI  - Dual impacts of climate change: forest migration and turnover through life
      history.
AB  - Tree species are predicted to track future climate by shifting their geographic
      distributions, but climate-mediated migrations are not apparent in a recent
      continental-scale analysis. To better understand the mechanisms of a possible
      migration lag, we analyzed relative recruitment patterns by comparing juvenile
      and adult tree abundances in climate space. One would expect relative recruitment
      to be higher in cold and dry climates as a result of tree migration with
      juveniles located further poleward than adults. Alternatively, relative
      recruitment could be higher in warm and wet climates as a result of higher tree
      population turnover with increased temperature and precipitation. Using the USDA
      Forest Service's Forest Inventory and Analysis data at regional scales, we
      jointly modeled juvenile and adult abundance distributions for 65 tree species in
      climate space of the eastern United States. We directly compared the optimal
      climate conditions for juveniles and adults, identified the climates where each
      species has high relative recruitment, and synthesized relative recruitment
      patterns across species. Results suggest that for 77% and 83% of the tree
      species, juveniles have higher optimal temperature and optimal precipitation,
      respectively, than adults. Across species, the relative recruitment pattern is
      dominated by relatively more abundant juveniles than adults in warm and wet
      climates. These different abundance-climate responses through life history are
      consistent with faster population turnover and inconsistent with the geographic
      trend of large-scale tree migration. Taken together, this juvenile-adult analysis
      suggests that tree species might respond to climate change by having faster
      turnover as dynamics accelerate with longer growing seasons and higher
      temperatures, before there is evidence of poleward migration at biogeographic
      scales.

PMID- 24014499
TI  - Comparative validity of the chinese versions of the bulimic inventory test
      edinburgh and eating attitudes test for DSM-IV eating disorders among high school
      dance and nondance students in Taiwan.
AB  - OBJECTIVES: To compare the validity of the Eating Attitudes Test (EAT) and the
      Bulimic Investigatory Test Edinburgh (BITE) as screening tools for eating
      disorders (EDs), and to identify a new threshold for each questionnaire to detect
      ED cases among dance and nondance students. METHOD: Dance students enrolled in
      high schools with gifted dance programs and nondance students randomly chosen
      from the same or nearby schools were invited to participate in a 2-phase ED
      survey. Participants completed the EAT and BITE questionnaires in the first
      phase. All participants who screened positive and 10% of the participants who
      screened negative were interviewed blindly using the Structured Clinical
      Interview for DSM-IV-TR Axis I Disorders Patient Edition. RESULTS: The BITE had
      better accuracy than the EAT in detecting ED in general among both dance and non
      dance students. BITE scores of 19 and 16 were the optimal cutoff values for
      determining ED among dance and nondance students, respectively. The optimal
      cutoff value for the EAT to diagnose an ED was 19 for dance students and 12 for
      nondance students. Both questionnaires showed higher sensitivity and lower
      specificity in dance students than nondance students at the same cutoff points.
      DISCUSSION: The BITE had better diagnostic performance than the EAT in this
      nonclinical population, although its ability to detect restrictive behaviors is
      likely as limited as that of the EAT. Plausible explanations for these results
      and limitations of this study are discussed in the text.

PMID- 24014500
TI  - Advances in pathogenesis and therapy of hemolytic uremic syndrome caused by Shiga
      toxin-2.
AB  - Shiga toxin (Stx) producing Escherichia coli (STEC) is responsible to bloody
      diarrhea (hemorrhagic colitis) and the hemolytic uremic syndrome (HUS). STEC
      strains carry inducible lambda phages integrated into their genomes that encode
      Stx 1 and/or 2, with several allelic variants each one. O157:H7 is the serotype
      that was documented in the vast majority of HUS cases although non-O157 serotypes
      have been increasingly reported to account for HUS cases. However, the outbreak
      that occurred in central Europe during late spring of 2011 showed that the
      pathogen was E. coli O104:H4. More than 4,000 persons were infected mainly in
      Germany, and it produced more than 900 cases of HUS resulting in 54 deaths. E.
      coli O104:H4 is a hybrid organism that combines some of the virulence genes of
      STEC and enteroaggregative E. coli specially production of Stx2 and the adherence
      mechanisms to intestinal epithelium. The differences in the epidemiology and
      presentation of E. coli pathogen meant a challenge for public health and
      scientific research to increase the knowledge of HUS-pathophysiology and to
      improve available therapies to treat HUS.

PMID- 24014501
TI  - Service attachment: the relative contributions of ward climate perceptions and
      attachment anxiety and avoidance in male inpatients with psychosis.
AB  - BACKGROUND: It has been suggested that mental health services can help meet the
      attachment needs of inpatients and improve patient outcomes through the provision
      of a 'secure base'; however, what defines the latter is unclear. Perception of
      ward climate might be a useful indicator. AIM: The aim of this study was to
      examine whether inpatient perceptions of the ward climate, which is partly under
      the control of the service, or inpatients' own personal levels of attachment
      anxiety and avoidance are more associated with their attachment to their service.
      METHOD: Seventy-six men diagnosed with a psychotic illness, who were residents in
      one of four regional medium-security units in England, completed questionnaire
      measures of service attachment, personal attachment style and ward climate.
      RESULTS: Ward climate was more strongly associated with service attachment than
      personal levels of attachment anxiety and avoidance. The most important aspect of
      ward climate for service attachment was the depth and influence of staff support
      for the inpatients. CONCLUSIONS: Although patient characteristics are important
      influences on development of service attachment, ward climate is also important.
      The latter may be easily and reliably monitored with a brief questionnaire.
      Strategies to enhance and maintain its positive components are likely to be
      important for progress with forensic hospital inpatients who have a psychotic
      illness.

PMID- 24014502
TI  - Feeling the need ... the need for speed (of processing training) in Parkinson
      disease.

PMID- 24014503
TI  - Randomized trial of cognitive speed of processing training in Parkinson disease.
AB  - OBJECTIVE: To examine the efficacy of cognitive speed of processing training
      (SOPT) among individuals with Parkinson disease (PD). Moderators of SOPT were
      also examined. METHODS: Eighty-seven adults, 40 years of age or older, with a
      diagnosis of idiopathic PD in Hoehn & Yahr stages 1-3 and on a stable medication
      regimen were randomized to either 20 hours of self-administered SOPT (using
      InSight software) or a no-contact control condition. Participants were assessed
      at baseline and after 3 months of training (or an equivalent delay). The primary
      outcome measure was useful field of view test (UFOV) performance, and secondary
      outcomes included cognitive self-perceptions and depressive symptoms. RESULTS:
      Results indicated that participants randomized to SOPT experienced significantly
      greater improvements on UFOV performance relative to controls, Wilks lambda =
      0.938, F 1,72 = 4.79, p = 0.032, partial eta(2) = 0.062. Findings indicated no
      significant effect of training on secondary outcomes, Wilks lambda = 0.987, F2,70
      < 1, p = 0.637, partial eta(2) = 0.013. CONCLUSIONS: Patients with mild to
      moderate stage PD can self-administer SOPT and improve their cognitive speed of
      processing, as indexed by UFOV (a robust predictor of driving performance in
      aging and PD). Further research should establish if persons with PD experience
      longitudinal benefits of such training and if improvements translate to benefits
      in functional activities such as driving. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that SOPT improves UFOV performance among persons in
      the mild to moderate stages of PD.

PMID- 24014505
TI  - Anti-[2.2](1,4)pentacenophane: a covalently coupled pentacene dimer.
AB  - Two in a row: A pentacene dimer in which both units are covalently linked through
      a [2.2]paracyclophane bridge, has been synthesized. The electronic properties of
      the molecule were elucidated by a combination of experimental and computational
      methods. Such molecules could lead to materials with improved charge-transport
      properties. 

PMID- 24014504
TI  - Epstein-Barr virus in oral shedding of children with multiple sclerosis.
AB  - OBJECTIVE: To investigate Epstein-Barr virus (EBV) oral shedding frequency and
      EBV genetic diversity in pediatric patients with multiple sclerosis (MS).
      METHODS: This was a prospective case-control study. We used PCR-based assays to
      detect viral DNA in the monthly mouth swabs of 22 pediatric patients with MS and
      77 age- and sex-matched healthy controls. EBV-positive samples were further
      analyzed for sequence variation in the EBV BCRF1 (ebvIL-10) gene using direct DNA
      sequencing methods, and in the EBV LMP1 gene by mass spectrometry. RESULTS:
      Nineteen of the 22 (86.4%) children with MS were seropositive for remote EBV
      infection compared to 35 out of 77 (45.5%) healthy controls (p = 0.008). Baseline
      analysis of mouth swabs revealed a higher proportion of EBV-positive samples from
      EBV-seropositive patients with MS compared to EBV-seropositive healthy controls
      (52.6% vs 20%, p = 0.007). Longitudinal analysis of monthly swabs revealed
      average EBV detection rates of 50.6% in patients with MS and 20.4% in controls (p
      = 0.01). The oral shedding frequencies of Herpesviruses herpes simplex virus-1,
      cytomegalovirus, human herpesvirus (HHV)-6, and HHV-7 did not differ between
      groups. Changes in the predominant EBV genetic variants were detected more
      frequently in patients with MS; however, no specific EBV genetic variant was
      preferentially associated with MS. CONCLUSION: Children with MS demonstrate
      abnormally increased rates of EBV viral reactivation and a broader range of
      genetic variants, suggesting a selective impairment in their immunologic control
      of EBV.

PMID- 24014506
TI  - Regional brain atrophy in mouse models of neuronal ceroid lipofuscinosis: a new
      rostrocaudal perspective.
AB  - The neuronal ceroid lipofuscinoses (Batten disease) are collectively the most
      common inherited neurodegenerative disorder of childhood. Mouse models of
      neuronal ceroid lipofuscinosis represent a powerful resource for investigating
      the underlying disease mechanisms, which remain poorly understood. Here we
      present a new rostrocaudal analysis of regional brain volume rather than focusing
      on central nervous system structures that can be affected. This has revealed an
      earlier onset of regional atrophy than was suspected in infantile neuronal ceroid
      lipofuscinosis (or CLN1 disease, infantile), with a greater involvement of
      rostral structures. We have also provided the first description of regional
      atrophy in severely affected mice with the juvenile variant (CLN3 disease,
      juvenile). These data reveal new perspectives on how the central nervous system
      is affected in these disorders, which have implications for judging the efficacy
      of therapeutic strategies in preclinical studies. 

PMID- 24014507
TI  - Large animal models for Batten disease: a review.
AB  - The neuronal ceroid lipofuscinoses, collectively referred to as Batten disease,
      make up a group of inherited childhood disorders that result in blindness, motor
      and cognitive regression, brain atrophy, and seizures, ultimately leading to
      premature death. So far more than 10 genes have been implicated in different
      forms of the neuronal ceroid lipofuscinoses. Most related research has involved
      mouse models, but several naturally occurring large animal models have recently
      been discovered. In this review, we discuss the different large animal models and
      their significance in Batten disease research. 

PMID- 24014508
TI  - Neurobehavioral features and natural history of juvenile neuronal ceroid
      lipofuscinosis (Batten disease).
AB  - Juvenile neuronal ceroid lipofuscinosis is a childhood-onset neurodegenerative
      disease with prominent symptoms comprising a pediatric dementia syndrome:
      intellectual decline, mood and behavioral impairments, and loss of adaptive
      skills. We review the history of neurobehavioral features in juvenile neuronal
      ceroid lipofuscinosis and the work of the University of Rochester Batten Center
      to characterize the extent and progression of neurobehavioral symptoms over the
      disease course, and discuss the relevance of neurobehavioral studies as an aid to
      understanding the clinical phenotype of juvenile Batten disease and potential
      targets for intervention. 

PMID- 24014509
TI  - Clinical trials in rare disease: challenges and opportunities.
AB  - The neuronal ceroid lipofuscinoses constitute one of many groups of rare
      childhood diseases for which disease-modifying treatments are nonexistent.
      Disease-specific barriers to therapeutic success include incomplete understanding
      of disease pathophysiology and limitations of treatments that cannot adequately
      cross the blood-brain barrier to access the central nervous system. Therapeutic
      development in the neuronal ceroid lipofuscinoses shares many challenges with
      other rare diseases, such as incomplete understanding of natural history to
      inform trial design, need for alternatives to the randomized controlled clinical
      trial, requirement for more sensitive outcome measures to quantify disease,
      limited access to resources required to mount a clinical trial (including
      funding), and difficulties of recruiting a small sample to participation.
      Solutions to these barriers will require multicenter collaboration, partnership
      with patient organizations, training a new generation of researchers interested
      in rare diseases, and leveraging existing resources. 

PMID- 24014510
TI  - Considerations for the treatment of infantile neuronal ceroid lipofuscinosis
      (infantile Batten disease).
AB  - The infantile form of neuronal ceroid lipofuscinosis (ie, infantile Batten
      disease) is the most rapidly progressing type and is caused by an inherited
      deficiency in the lysosomal enzyme palmitoyl protein thioesterase 1. The absence
      of enzyme activity leads to progressive accumulation of autofluorescent material
      in many cell types, particularly neurons of the central nervous system. Clinical
      signs of infantile neuronal ceroid lipofuscinosis appear between 6 months and 1
      year of age and include vision loss, cognitive decline, motor deficits, seizures,
      and premature death, typically by 3 to 5 years of age. There is currently no
      effective treatment. However, preclinical experiments in the murine model of
      infantile neuronal ceroid lipofuscinosis have shown that gene therapy, enzyme
      replacement, stem cell transplantation, and small-molecule drugs, alone or in
      combination, can significantly slow disease progression. A more thorough
      understanding of the underlying pathogenesis of infantile neuronal ceroid
      lipofuscinosis will identify new therapeutic targets. 

PMID- 24014511
TI  - Treatment of the Ppt1(-/-) mouse model of infantile neuronal ceroid
      lipofuscinosis with the N-methyl-D-aspartate (NMDA) receptor antagonist
      memantine.
AB  - The neuronal ceroid lipofuscinoses, a family of neurodegenerative lysosomal
      storage disorders, represent the most common cause of pediatric-onset
      neurodegeneration. The infantile form has a devastatingly early onset and one of
      the fastest-progressing disease courses. Despite decades of research, the
      molecular mechanisms driving neuronal loss in infantile neuronal ceroid
      lipofuscinosis remain unknown. We have previously shown that N-methyl-d-aspartate
      (NMDA)-type glutamate receptors in the Ppt1(-/-) mouse model of this disease
      exhibit a hyperfunctional phenotype and postulate that aberrant glutamatergic
      activity may contribute to neural pathology in both the mouse model and human
      patients. To test this hypothesis, we treated Ppt1(-/-) mice with the NMDA
      receptor antagonist memantine and assessed their response to the drug using an
      accelerating rotarod. At 20 mg/kg, memantine treatment induced a delayed but
      notable improvement in Ppt1(-/-) mice. Much remains to be assessed before moving
      to patient trials, but these results suggest memantine has potential as a
      treatment. 

PMID- 24014513
TI  - "Being responsible, respectful, trying to keep the tradition alive:" cultural
      resilience and growing up in an Alaska Native community.
AB  - Indigenous circumpolar youth are experiencing challenges of growing up in a
      context much different from that of their parents and their grandparents due to
      rapid and imposed social change. Our study is interested in community resilience:
      the meaning systems, resources, and relationships that structure how youth go
      about overcoming difficulties. The research reflects an understanding that social
      and cultural ecologies influence people's available and meaningful options. The
      in-depth, qualitative study of 20 youth from the same Arctic community shows
      Inupiat (Alaska Native) youth are navigating challenges. Findings from this
      research suggest that Inupiat youth reflect more flexible patterns of resilience
      when they are culturally grounded. This cultural foundation involves kinship
      networks that mediate young people's access to cultural and material assets. Our
      participants emphasized the importance of taking care of others and "giving back
      to the community." Being "in the country" linked youth to traditional ontology
      that profoundly shifted how youth felt in relation to themselves, to others, and
      the world. The vast majority of participants' "fulfillment narratives" centered
      on doing subsistence and/or cultural activities. In relation to this, young
      people were more likely to demonstrate versatility in their resilience strategies
      when deploying coherent self-narratives that reflected novel yet culturally
      resonant styles. Young women were more likely to demonstrate this by
      reconfiguring notions of culture and gender identity in ways that helped them
      meet challenges in their lives. Lastly, generational differences in
      understandings signal particular ways that young people's historical and
      political positioning influences their access to cultural resources. 

PMID- 24014514
TI  - Looking across three generations of Alaska Natives to explore how culture fosters
      indigenous resilience.
AB  - Research has established connection between indigenous culture--often described
      in terms of cultural identity, enculturation, and participation in traditional
      activities--and resilience, the process by which people overcome acute and
      ongoing challenges. Despite correlations between culture and resilience, research
      has seldom described the ways these concepts are linked in indigenous people's
      narratives. Furthermore, little attention has been paid to the affect of
      historical trauma on different generations' understanding and deployment of
      "culture" in the context of hardship. This project, conducted in the summer of
      2008 in an indigenous Arctic community, focuses on narratives from three
      generations who have experienced different degrees of cultural suppression in
      their lifetimes. From this starting point, the study explores how individuals
      make meaning and take strength from particular notions of culture, and
      illuminates the ways each generation accesses and deploys their cultural
      understandings in the face of hardship. By identifying the similarities and
      differences in both the challenges and sources of strength for each generation,
      the paper highlights how understandings of culture are shaped by historical
      experiences and modified through time. The differing ways that culture fosters
      strength, purpose, and fortitude (or does not) in indigenous young people's,
      adults' and Elders' life stories provide clues for enhancing indigenous youth
      resilience. Findings suggest that "culture" can galvanize Inupiaq people's sense
      of identity, feeling of commitment, and purpose, all of which are protective.
      However, young people need support in developing particular ideas around cultural
      identity and group membership that can contribute to resilience.

PMID- 24014515
TI  - Making hospitals in China smoke-free: a prospective study of implementing the new
      standard.
AB  - OBJECTIVES: In the run-up to all Chinese health care facilities becoming smoke
      free, the feasibility of the new standard was assessed by monitoring its
      implementation in a sample of Chinese hospitals. METHODS: Forty-one hospitals
      across 20 provinces were asked to ban smoking inside the hospital and provide
      advice and referral to stop-smoking treatment. Smoking status of more than 24,000
      members of staff at 21 hospitals was surveyed at baseline (April 2009) and at
      follow-up (October 2010). Surveys monitored implementation of several specific
      aspects of the new standard to identify potential barriers to nationwide
      implementation. RESULTS: All hospitals managed to implement the ban and most set
      up smoking cessation clinics. Routine recording of patients' smoking status
      proved more difficult to implement. The hospitals improved significantly in 8 out
      of 11 monitored policy parameters. Smoking prevalence among staff decreased from
      14.8% to 10.7% (p < .001), suggesting an important collateral benefit of making
      hospitals smoke-free. Outdoor smoking areas facilitated the indoor ban. Staff
      education emerged as the key priority. CONCLUSIONS: The smoke-free standard is
      feasible even in a country with a widespread acceptance of smoking inside health
      facilities. Several challenges need to be addressed when the new standard is
      disseminated across China.

PMID- 24014516
TI  - Isolated intraneural schwannoma of the median nerve.

PMID- 24014517
TI  - Spontaneous, isolated rupture of the flexor digitorum superficialis tendon in
      zone II and annular pulley ruptures.

PMID- 24014519
TI  - Faciobrachial dystonic seizures: the influence of immunotherapy on seizure
      control and prevention of cognitive impairment in a broadening phenotype.
AB  - Voltage-gated potassium channel complex antibodies, particularly those directed
      against leucine-rich glioma inactivated 1, are associated with a common form of
      limbic encephalitis that presents with cognitive impairment and seizures.
      Faciobrachial dystonic seizures have recently been reported as immunotherapy
      responsive, brief, frequent events that often predate the cognitive impairment
      associated with this limbic encephalitis. However, these observations were made
      from a retrospective study without serial cognitive assessments. Here, we
      undertook the first prospective study of faciobrachial dystonic seizures with
      serial assessments of seizure frequencies, cognition and antibodies in 10 cases
      identified over 20 months. We hypothesized that (i) faciobrachial dystonic
      seizures would show a differential response to anti-epileptic drugs and
      immunotherapy; and that (ii) effective treatment of faciobrachial dystonic
      seizures would accelerate recovery and prevent the development of cognitive
      impairment. The 10 cases expand both the known age at onset (28 to 92 years,
      median 68) and clinical features, with events of longer duration, simultaneously
      bilateral events, prominent automatisms, sensory aura, and post-ictal fear and
      speech arrest. Ictal epileptiform electroencephalographic changes were present in
      three cases. All 10 cases were positive for voltage-gated potassium channel
      complex antibodies (346-4515 pM): nine showed specificity for leucine-rich glioma
      inactivated 1. Seven cases had normal clinical magnetic resonance imaging, and
      the cerebrospinal fluid examination was unremarkable in all seven tested.
      Faciobrachial dystonic seizures were controlled more effectively with
      immunotherapy than anti-epileptic drugs (P = 0.006). Strikingly, in the nine
      cases who remained anti-epileptic drug refractory for a median of 30 days (range
      11-200), the addition of corticosteroids was associated with cessation of
      faciobrachial dystonic seizures within 1 week in three and within 2 months in six
      cases. Voltage-gated potassium channel-complex antibodies persisted in the four
      cases with relapses of faciobrachial dystonic seizures during corticosteroid
      withdrawal. Time to recovery of baseline function was positively correlated with
      time to immunotherapy (r = 0.74; P = 0.03) but not time to anti-epileptic drug
      administration (r = 0.55; P = 0.10). Of 10 cases, the eight cases who received
      anti-epileptic drugs (n = 3) or no treatment (n = 5) all developed cognitive
      impairment. By contrast, the two who did not develop cognitive impairment
      received immunotherapy to treat their faciobrachial dystonic seizures (P = 0.02).
      In eight cases without clinical magnetic resonance imaging evidence of
      hippocampal signal change, cross-sectional volumetric magnetic resonance imaging
      post-recovery, after accounting for age and head size, revealed cases (n = 8) had
      smaller brain volumes than healthy controls (n = 13) (P < 0.001). In conclusion,
      faciobrachial dystonic seizures can be prospectively identified as a form of
      epilepsy with an expanding phenotype. Immunotherapy is associated with excellent
      control of the frequently anti-epileptic drug refractory seizures, hastens time
      to recovery, and may prevent the subsequent development of cognitive impairment
      observed in this study. 

PMID- 24014520
TI  - The value of magnetoencephalography for seizure-onset zone localization in
      magnetic resonance imaging-negative partial epilepsy.
AB  - Surgical treatment of epilepsy is a challenge for patients with non-contributive
      brain magnetic resonance imaging. However, surgery is feasible if the seizure
      onset zone is precisely delineated through intracranial electroencephalography
      recording. We recently described a method, volumetric imaging of epileptic
      spikes, to delineate the spiking volume of patients with focal epilepsy using
      magnetoencephalography. We postulated that the extent of the spiking volume
      delineated with volumetric imaging of epileptic spikes could predict the
      localizability of the seizure-onset zone by intracranial electroencephalography
      investigation and outcome of surgical treatment. Twenty-one patients with non
      contributive magnetic resonance imaging findings were included. All patients
      underwent intracerebral electroencephalography investigation through
      stereotactically implanted depth electrodes (stereo-electroencephalography) and
      magnetoencephalography with delineation of the spiking volume using volumetric
      imaging of epileptic spikes. We evaluated the spatial congruence between the
      spiking volume determined by magnetoencephalography and the localization of the
      seizure-onset zone determined by stereo-electroencephalography. We also evaluated
      the outcome of stereo-electroencephalography and surgical treatment according to
      the extent of the spiking volume (focal, lateralized but non-focal or non
      lateralized). For all patients, we found a spatial overlap between the seizure
      onset zone and the spiking volume. For patients with a focal spiking volume, the
      seizure-onset zone defined by stereo-electroencephalography was clearly localized
      in all cases and most patients (6/7, 86%) had a good surgical outcome.
      Conversely, stereo-electroencephalography failed to delineate a seizure-onset
      zone in 57% of patients with a lateralized spiking volume, and in the two
      patients with bilateral spiking volume. Four of the 12 patients with non-focal
      spiking volumes were operated upon, none became seizure-free. As a whole,
      patients having focal magnetoencephalography results with volumetric imaging of
      epileptic spikes are good surgical candidates and the implantation strategy
      should incorporate volumetric imaging of epileptic spikes results. On the
      contrary, patients with non-focal magnetoencephalography results are less likely
      to have a localized seizure-onset zone and stereo electroencephalography is not
      advised unless clear localizing information is provided by other presurgical
      investigation methods. 

PMID- 24014518
TI  - Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic
      variation around SCN1A.
AB  - Epilepsy comprises several syndromes, amongst the most common being mesial
      temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal
      lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial
      temporal lobe epilepsy with hippocampal sclerosis is frequently associated with
      important co-morbidities, mandating the search for better understanding and
      treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis
      is unknown, but there is an association with childhood febrile seizures. Several
      rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A,
      which encodes a brain-expressed sodium channel subunit targeted by many anti
      epileptic drugs. We undertook a genome-wide association study in 1018 people with
      mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control
      subjects, with validation in an independent sample set comprising 959 people with
      mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control
      subjects. To dissect out variants related to a history of febrile seizures, we
      tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with
      (overall n = 757) and without (overall n = 803) a history of febrile seizures.
      Meta-analysis revealed a genome-wide significant association for mesial temporal
      lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium
      channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the
      SCN1A gene, P = 3.36 * 10(-9), odds ratio (A) = 1.42, 95% confidence interval:
      1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not
      develop epilepsy during prospective follow-up to age 13 years, and 6456 controls,
      no association was found for rs7587026 and febrile seizures. These findings
      suggest SCN1A involvement in a common epilepsy syndrome, give new direction to
      biological understanding of mesial temporal lobe epilepsy with hippocampal
      sclerosis with febrile seizures, and open avenues for investigation of prognostic
      factors and possible prevention of epilepsy in some children with febrile
      seizures. 

PMID- 24014521
TI  - Correlation of dopaminergic terminal dysfunction and microstructural
      abnormalities of the basal ganglia and the olfactory tract in Parkinson's
      disease.
AB  - Signal abnormalities of the substantia nigra and the olfactory tract detected
      either by diffusion tensor imaging, including measurements of mean diffusivity, a
      parameter of brain tissue integrity, and fractional anisotropy, a parameter of
      neuronal fibre integrity, or transcranial sonography, were recently reported in
      the early stages of Parkinson's disease. In this study, changes in the nigral and
      olfactory diffusion tensor signal, as well as nigral echogenicity, were
      correlated with clinical scales of motor disability, odour function and putaminal
      dopamine storage capacity measured with 6-[(18)F] fluorolevodopa positron
      emission tomography in early and advanced stages of Parkinson's disease.
      Diffusion tensor imaging, transcranial sonography and positron emission
      tomography were performed on 16 patients with Parkinson's disease (mean disease
      duration 3.7 +/- 3.7 years, Hoehn and Yahr stage 1 to 4) and 14 age-matched
      healthy control subjects. Odour function was measured by the standardized
      Sniffin' Sticks Test. Mean putaminal 6-[(18)F] fluorolevodopa influx constant,
      mean nigral echogenicity, mean diffusivity and fractional anisotropy values of
      the substantia nigra and the olfactory tract were identified by region of
      interest analysis. When compared with the healthy control group, the Parkinson's
      disease group showed significant signal changes in the caudate and putamen by 6
      [(18)F] fluorolevodopa positron emission tomography, in the substantia nigra by
      transcranial sonography, mean diffusivity and fractional anisotropy (P < 0.001, P
      < 0.01, P < 0.05, respectively) and in the olfactory tract by mean diffusivity (P
      < 0.05). Regional mean diffusivity values of the substantia nigra and the
      olfactory tract correlated significantly with putaminal 6-[(18)F] fluorolevodopa
      uptake (r = -0.52, P < 0.05 and r = -0.71, P < 0.01). Significant correlations
      were also found between nigral mean diffusivity values and the Unified
      Parkinson's Disease Rating Scale motor score (r = -0.48, P < 0.01) and between
      mean putaminal 6-[(18)F] fluorolevodopa uptake and the total odour score (r =
      0.58; P < 0.05) as well as the Unified Parkinson's Disease Rating Scale motor
      score (r = -0.53, P < 0.05). This study reports a significant association between
      increased mean diffusivity signal and decreased 6-[(18)F] fluorolevodopa uptake,
      indicating that microstructural degradation of the substantia nigra and the
      olfactory tract parallels progression of putaminal dopaminergic dysfunction in
      Parkinson's disease. Since increases in nigral mean diffusivity signal also
      correlated with motor dysfunction, diffusion tensor imaging may serve as a
      surrogate marker for disease progression in future studies of putative disease
      modifying therapies. 

PMID- 24014522
TI  - Hybrid treatment in a patient with acute aortic syndrome and an aberrant right
      subclavian artery.
AB  - A 57-year-old man was admitted to our department with recent onset of chest pain.
      Computed tomography (CT) scans revealed an acute aortic syndrome manifested by a
      penetrating atherosclerotic ulcer and contained rupture at the level of origin of
      an aberrant right subclavian artery. A combined vascular and endovascular
      approach was selected. The entire arch was rerouted, a reversed bifurcated Dacron
      prosthesis was placed, and a bypass was created between the right common carotid
      artery and the lusorian artery, followed by thoracic endovascular aortic repair.
      The clinical course was uneventful. The CT scan obtained after the procedure
      revealed regular supra-aortic perfusion and complete exclusion of the complex
      lesion. 

PMID- 24014523
TI  - Retrievable stent technique and coil embolization of high-flow iatrogenic
      cervical vertebral arteriovenous fistula: technical note.
AB  - Cervical vertebral arteriovenous fistulas (VAFs) are rare clinical entities
      between the vertebral artery and veins of the neighborhood. We report the first
      approach in the literature experience in the treatment of high-flow VAF caused by
      percutaneous catheterization of the internal jugular vein, which was successfully
      occluded with coils and Solitaire AB neurovascular remodeling device system that
      can be fully retrieved even when fully deployed for procedural control. Complete
      angiographic and clinical cure was achieved, and no complications related to the
      new embolization procedure occurred. 

PMID- 24014525
TI  - Tomato fruit and seed colonization by Clavibacter michiganensis subsp.
      michiganensis through external and internal routes.
AB  - The Gram-positive bacterium Clavibacter michiganensis subsp. michiganensis,
      causal agent of bacterial wilt and canker of tomato, is an economically
      devastating pathogen that inflicts considerable damage throughout all major
      tomato-producing regions. Annual outbreaks continue to occur in New York, where
      C. michiganensis subsp. michiganensis spreads via infected transplants,
      trellising stakes, tools, and/or soil. Globally, new outbreaks can be accompanied
      by the introduction of contaminated seed stock; however, the route of seed
      infection, especially the role of fruit lesions, remains undefined. In order to
      investigate the modes of seed infection, New York C. michiganensis subsp.
      michiganensis field strains were stably transformed with a gene encoding enhanced
      green fluorescent protein (eGFP). A constitutively eGFP-expressing virulent C.
      michiganensis subsp. michiganensis isolate, GCMM-22, was used to demonstrate that
      C. michiganensis subsp. michiganensis could not only access seeds systemically
      through the xylem but also externally through tomato fruit lesions, which
      harbored high intra- and intercellular populations. Active movement and expansion
      of bacteria into the fruit mesocarp and nearby xylem vessels followed, once the
      fruits began to ripen. These results highlight the ability of C. michiganensis
      subsp. michiganensis to invade tomato fruits and seeds through multiple entry
      routes. 

PMID- 24014524
TI  - Insights into the mode of action of benzyl isothiocyanate on Campylobacter
      jejuni.
AB  - Campylobacter jejuni is a widespread pathogen responsible for most of the food
      borne gastrointestinal diseases in Europe. The use of natural antimicrobial
      molecules is a promising alternative to antibiotic treatments for pathogen
      control in the food industry. Isothiocyanates are natural antimicrobial
      compounds, which also display anticancer activity. Several studies described the
      chemoprotective effect of isothiocyanates on eukaryotic cells, but the
      antimicrobial mechanism is still poorly understood. We investigated the early
      cellular response of C. jejuni to benzyl isothiocyanate by both transcriptomic
      and physiological approaches. The transcriptomic response of C. jejuni to benzyl
      isothiocyanate showed upregulation of heat shock response genes and an impact on
      energy metabolism. Oxygen consumption was progressively impaired by benzyl
      isothiocyanate treatment, as revealed by high-resolution respirometry, while the
      ATP content increased soon after benzyl isothiocyanate exposition, which suggests
      a shift in the energy metabolism balance. Finally, benzyl isothiocyanate induced
      intracellular protein aggregation. These results indicate that benzyl
      isothiocyanate affects C. jejuni by targeting proteins, resulting in the
      disruption of major metabolic processes and eventually leading to cell death. 

PMID- 24014526
TI  - Efficient production of Bacillus thuringiensis Cry1AMod toxins under regulation
      of cry3Aa promoter and single cysteine mutations in the protoxin region.
AB  - Bacillus thuringiensis Cry1AbMod toxins are engineered versions of Cry1Ab that
      lack the amino-terminal end, including domain I helix alpha-1 and part of helix
      alpha-2. This deletion improves oligomerization of these toxins in solution in
      the absence of cadherin receptor and counters resistance to Cry1A toxins in
      different lepidopteran insects, suggesting that oligomerization plays a major
      role in their toxicity. However, Cry1AbMod toxins are toxic to Escherichia coli
      cells, since the cry1A promoter that drives its expression in B. thuringiensis
      has readthrough expression activity in E. coli, making difficult the construction
      of these CryMod toxins. In this work, we show that Cry1AbMod and Cry1AcMod toxins
      can be cloned efficiently under regulation of the cry3A promoter region to drive
      its expression in B. thuringiensis without expression in E. coli cells. However,
      p3A-Cry1Ab(c)Mod construction promotes the formation of Cry1AMod crystals in B.
      thuringiensis cells that were not soluble at pH 10.5 and showed no toxicity to
      Plutella xylostella larvae. Cysteine residues in the protoxin carboxyl-terminal
      end of Cry1A toxins have been shown to be involved in disulfide bond formation,
      which is important for crystallization. Six individual cysteine substitutions for
      serine residues were constructed in the carboxyl-terminal protoxin end of the p3A
      Cry1AbMod construct and one in the carboxyl-terminal protoxin end of p3A
      Cry1AcMod. Interestingly, p3A-Cry1AbMod C654S and C729S and p3A-Cry1AcMod C730S
      recover crystal solubility at pH 10.5 and toxicity to P. xylostella. These
      results show that combining the cry3A promoter expression system with single
      cysteine mutations is a useful system for efficient expression of Cry1AMod toxins
      in B. thuringiensis. 

PMID- 24014527
TI  - Isolation of butanol- and isobutanol-tolerant bacteria and physiological
      characterization of their butanol tolerance.
AB  - Despite their importance as a biofuel production platform, only a very limited
      number of butanol-tolerant bacteria have been identified thus far. Here, we
      extensively explored butanol- and isobutanol-tolerant bacteria from various
      environmental samples. A total of 16 aerobic and anaerobic bacteria that could
      tolerate greater than 2.0% (vol/vol) butanol and isobutanol were isolated. A 16S
      rRNA gene sequencing analysis revealed that the isolates were phylogenetically
      distributed over at least nine genera: Bacillus, Lysinibacillus,
      Rummeliibacillus, Brevibacillus, Coprothermobacter, Caloribacterium,
      Enterococcus, Hydrogenoanaerobacterium, and Cellulosimicrobium, within the phyla
      Firmicutes and Actinobacteria. Ten of the isolates were phylogenetically distinct
      from previously identified butanol-tolerant bacteria. Two relatively highly
      butanol-tolerant strains CM4A (aerobe) and GK12 (obligate anaerobe) were
      characterized further. Both strains changed their membrane fatty acid composition
      in response to butanol exposure, i.e., CM4A and GK12 exhibited increased
      saturated and cyclopropane fatty acids (CFAs) and long-chain fatty acids,
      respectively, which may serve to maintain membrane fluidity. The gene (cfa)
      encoding CFA synthase was cloned from strain CM4A and expressed in Escherichia
      coli. The recombinant E. coli showed relatively higher butanol and isobutanol
      tolerance than E. coli without the cfa gene, suggesting that cfa can confer
      solvent tolerance. The exposure of strain GK12 to butanol by consecutive passages
      even enhanced the growth rate, indicating that yet-unknown mechanisms may also
      contribute to solvent tolerance. Taken together, the results demonstrate that a
      wide variety of butanol- and isobutanol-tolerant bacteria that can grow in 2.0%
      butanol exist in the environment and have various strategies to maintain
      structural integrity against detrimental solvents. 

PMID- 24014528
TI  - Noninvasive analysis of microbiome dynamics in the fruit fly Drosophila
      melanogaster.
AB  - The diversity and structure of the intestinal microbial community has a strong
      influence on life history. To understand how hosts and microbes interact, model
      organisms with comparatively simple microbial communities, such as the fruit fly
      (Drosophila melanogaster), offer key advantages. However, studies of the
      Drosophila microbiome are limited to a single point in time, because flies are
      typically sacrificed for DNA extraction. In order to test whether noninvasive
      approaches, such as sampling of fly feces, could be a means to assess fly
      associated communities over time on the same cohort of flies, we compared the
      microbial communities of fly feces, dissected fly intestines, and whole flies
      across three different Drosophila strains. Bacterial species identified in either
      whole flies or isolated intestines were reproducibly found in feces samples.
      Although the bacterial communities of feces and intestinal samples were not
      identical, they shared similarities and obviously the same origin. In contrast to
      material from whole flies and intestines, feces samples were not compromised by
      Wolbachia spp. infections, which are widespread in laboratory and wild strains.
      In a proof-of-principle experiment, we showed that simple nutritional
      interventions, such as a high-fat diet or short-term starvation, had drastic and
      long-lasting effects on the micobiome. Thus, the analysis of feces can supplement
      the toolbox for microbiome studies in Drosophila, unleashing the full potential
      of such studies in time course experiments where multiple samples from single
      populations are obtained during aging, development, or experimental
      manipulations. 

PMID- 24014529
TI  - Unraveling the Leloir pathway of Bifidobacterium bifidum: significance of the
      uridylyltransferases.
AB  - The GNB/LNB (galacto-N-biose/lacto-N-biose) pathway plays a crucial role in
      bifidobacteria during growth on human milk or mucin from epithelial cells. It is
      thought to be the major route for galactose utilization in Bifidobacterium longum
      as it is an energy-saving variant of the Leloir pathway. Both pathways are
      present in B. bifidum, and galactose 1-phosphate (gal1P) is considered to play a
      key role. Due to its toxic nature, gal1P is further converted into its activated
      UDP-sugar through the action of poorly characterized uridylyltransferases. In
      this study, three uridylyltransferases (galT1, galT2, and ugpA) from
      Bifidobacterium bifidum were cloned in an Escherichia coli mutant and screened
      for activity on the key intermediate gal1P. GalT1 and GalT2 showed UDP-glucose
      hexose-1-phosphate uridylyltransferase activity (EC 2.7.7.12), whereas UgpA
      showed promiscuous UTP-hexose-1-phosphate uridylyltransferase activity (EC
      2.7.7.10). The activity of UgpA toward glucose 1-phosphate was about 33-fold
      higher than that toward gal1P. GalT1, as part of the bifidobacterial Leloir
      pathway, was about 357-fold more active than GalT2, the functional analog in the
      GNB/LNB pathway. These results suggest that GalT1 plays a more significant role
      than previously thought and predominates when B. bifidum grows on lactose and
      human milk oligosaccharides. GalT2 activity is required only during growth on
      substrates with a GNB core such as mucin glycans. 

PMID- 24014530
TI  - BopA does not have a major role in the adhesion of Bifidobacterium bifidum to
      intestinal epithelial cells, extracellular matrix proteins, and mucus.
AB  - The ability of bifidobacteria to adhere to the intestine of the human host is
      considered to be important for efficient colonization and achieving probiotic
      effects. Bifidobacterium bifidum strains DSM20456 and MIMBb75 adhere well to the
      human intestinal cell lines Caco-2 and HT-29. The surface lipoprotein BopA was
      previously described to be involved in mediating adherence of B. bifidum to
      epithelial cells, but thioacylated, purified BopA inhibited the adhesion of B.
      bifidum to epithelial cells in competitive adhesion assays only at very high
      concentrations, indicating an unspecific effect. In this study, the role of BopA
      in the adhesion of B. bifidum was readdressed. The gene encoding BopA was cloned
      and expressed without its lipobox and hydrophobic signal peptide in Escherichia
      coli, and an antiserum against the recombinant BopA was produced. The antiserum
      was used to demonstrate the abundant localization of BopA on the cell surface of
      B. bifidum. However, blocking of B. bifidum BopA with specific antiserum did not
      reduce adhesion of bacteria to epithelial cell lines, arguing that BopA is not an
      adhesin. Also, adhesion of B. bifidum to human colonic mucin and fibronectin was
      found to be BopA independent. The recombinant BopA bound only moderately to human
      epithelial cells and colonic mucus, and it failed to bind to fibronectin. Thus,
      our results contrast the earlier findings on the major role of BopA in adhesion,
      indicating that the strong adhesion of B. bifidum to epithelial cell lines is
      BopA independent. 

PMID- 24014531
TI  - Lineage and genogroup-defining single nucleotide polymorphisms of Escherichia
      coli O157:H7.
AB  - Escherichia coli O157:H7 is a zoonotic human pathogen for which cattle are an
      important reservoir host. Using both previously published and new sequencing
      data, a 48-locus single nucleotide polymorphism (SNP)-based typing panel was
      developed that redundantly identified 11 genogroups that span six of the eight
      lineages recently described for E. coli O157:H7 (J. L. Bono, T. P. Smith, J. E.
      Keen, G. P. Harhay, T. G. McDaneld, R. E. Mandrell, W. K. Jung, T. E. Besser, P.
      Gerner-Smidt, M. Bielaszewska, H. Karch, M. L. Clawson, Mol. Biol. Evol. 29:2047
      2062, 2012) and additionally defined subgroups within four of those lineages.
      This assay was applied to 530 isolates from human and bovine sources. The SNP
      based lineage groups were concordant with previously identified E. coli O157:H7
      genotypes identified by other methods and were strongly associated with carriage
      of specific Stx genes. Two SNP lineages (Ia and Vb) were disproportionately
      represented among cattle isolates, and three others (IIa, Ib, and IIb) were
      disproportionately represented among human clinical isolates. This 48-plex SNP
      assay efficiently and economically identifies biologically relevant lineages
      within E. coli O157:H7. 

PMID- 24014532
TI  - C1 metabolism in Corynebacterium glutamicum: an endogenous pathway for oxidation
      of methanol to carbon dioxide.
AB  - Methanol is considered an interesting carbon source in "bio-based" microbial
      production processes. Since Corynebacterium glutamicum is an important host in
      industrial biotechnology, in particular for amino acid production, we performed
      studies of the response of this organism to methanol. The C. glutamicum wild type
      was able to convert (13)C-labeled methanol to (13)CO2. Analysis of global gene
      expression in the presence of methanol revealed several genes of ethanol
      catabolism to be upregulated, indicating that some of the corresponding enzymes
      are involved in methanol oxidation. Indeed, a mutant lacking the alcohol
      dehydrogenase gene adhA showed a 62% reduced methanol consumption rate,
      indicating that AdhA is mainly responsible for methanol oxidation to
      formaldehyde. Further studies revealed that oxidation of formaldehyde to formate
      is catalyzed predominantly by two enzymes, the acetaldehyde dehydrogenase Ald and
      the mycothiol-dependent formaldehyde dehydrogenase AdhE. The Deltaald DeltaadhE
      and Deltaald DeltamshC deletion mutants were severely impaired in their ability
      to oxidize formaldehyde, but residual methanol oxidation to CO2 was still
      possible. The oxidation of formate to CO2 is catalyzed by the formate
      dehydrogenase FdhF, recently identified by us. Similar to the case with ethanol,
      methanol catabolism is subject to carbon catabolite repression in the presence of
      glucose and is dependent on the transcriptional regulator RamA, which was
      previously shown to be essential for expression of adhA and ald. In conclusion,
      we were able to show that C. glutamicum possesses an endogenous pathway for
      methanol oxidation to CO2 and to identify the enzymes and a transcriptional
      regulator involved in this pathway. 

PMID- 24014533
TI  - Fatty alcohols for wax esters in Marinobacter aquaeolei VT8: two optional routes
      in the wax biosynthesis pathway.
AB  - The biosynthesis of wax esters in bacteria is accomplished by a unique pathway
      that combines a fatty alcohol and a fatty acyl coenzyme A substrate. Previous in
      vitro enzymatic studies indicated that two different enzymes could be involved in
      the synthesis of the required fatty alcohol in Marinobacter aquaeolei VT8. In
      this study, we demonstrate through a series of gene deletions and transcriptional
      analysis that either enzyme is capable of fulfilling the role of providing the
      fatty alcohol required for wax ester biosynthesis in vivo, but evolution has
      clearly selected one of these, a previously characterized fatty aldehyde
      reductase, as the preferred enzyme to perform this reaction under typical wax
      ester-accumulating conditions. These results complement previous in vitro studies
      and provide the first glimpse into the role of each enzyme in vivo in the native
      organism. 

PMID- 24014534
TI  - Fungal diversity in permafrost and tallgrass prairie soils under experimental
      warming conditions.
AB  - Soil fungi play a major role in terrestrial ecosystem functioning through
      interactions with soil structure, plants, micro- and mesofauna, and nutrient
      cycling through predation, pathogenesis, mutualistic, and saprotrophic roles. The
      diversity of soil fungi was assessed by sequencing their 28S rRNA gene in Alaskan
      permafrost and Oklahoma tallgrass prairie soils at experimental sites where the
      effect of climate warming is under investigation. A total of 226,695 reads were
      classified into 1,063 genera, covering 62% of the reference data set. Using the
      Bayesian Classifier offered by the Ribosomal Database Project (RDP) with 50%
      bootstrapping classification confidence, approximately 70% of sequences were
      returned as "unclassified" at the genus level, although the majority (~65%) were
      classified at the class level, which provided insight into these lesser-known
      fungal lineages. Those unclassified at the genus level were subjected to BLAST
      analysis against the ARB-SILVA database, where ~50% most closely matched
      nonfungal taxa. Compared to the more abundant sequences, a higher proportion of
      rare operational taxonomic units (OTU) were successfully classified to genera at
      50% bootstrap confidence, indicating that the fungal rare biosphere in these
      sites is not composed of sequencing artifacts. There was no significant effect
      after 1 year of warming on the fungal community structure at both sites, except
      perhaps for a few minor members, but there was a significant effect of sample
      depth in the permafrost soils. Despite overall significant community structure
      differences driven by variations in OTU dominance, the prairie and permafrost
      soils shared 90% and 63% of all fungal sequences, respectively, indicating a
      fungal "seed bank" common between both sites. 

PMID- 24014535
TI  - Novel method for genomic promoter shuffling by using recyclable cassettes.
AB  - Genetic elements of interest can be introduced into the Saccharomyces cerevisiae
      genome via homologous recombination. The current method is to link such an
      element to a selectable marker gene to be integrated into the target locus.
      However, the marker gene in this method cannot be reused, which limits repeated
      manipulation of the yeast genome. An alternative method is to utilize a
      counterselectable gene, such as URA3, with flanking tandem repeats. After
      integration, URA3 along with one copy of the repeat can be popped out via
      internal recombination, leaving behind one copy of the unwanted repeat. Here we
      describe a novel concept of genetic element shuffling in which the tandem repeats
      are made of the desired genetic element, so that after integration and popping
      out, only one copy of the element remains at the desired locus to function. As a
      proof of principle, we constructed three recyclable cassettes (PPGK1-URA3-PPGK1,
      PGAL1-URA3-PGAL1, and PtetO7-URA3-PtetO7) and integrated them upstream of an
      engineered chromosomal PHIS3-mCherry-Myc locus. After promoter shuffling, the
      mCherry-Myc gene was regulated precisely as anticipated. 

PMID- 24014536
TI  - Resistance to quorum-quenching compounds.
AB  - Bacteria have the remarkable ability to communicate as a group in what has become
      known as quorum sensing (QS), and this trait has been associated with important
      bacterial phenotypes, such as virulence and biofilm formation. Bacteria also have
      an incredible ability to evolve resistance to all known antimicrobials. Hence,
      although inhibition of QS has been hailed as a means to reduce virulence in a
      manner that is impervious to bacterial resistance mechanisms, this approach is
      unlikely to be a panacea. Here we review the evidence that bacteria can evolve
      resistance to quorum-quenching compounds. 

PMID- 24014537
TI  - Survival of murine norovirus, Tulane virus, and hepatitis A virus on alfalfa
      seeds and sprouts during storage and germination.
AB  - Human norovirus (huNoV) and hepatitis A virus (HAV) have been involved in several
      produce-associated outbreaks and identified as major food-borne viral etiologies.
      In this study, the survival of huNoV surrogates (murine norovirus [MNV] and
      Tulane virus [TV]) and HAV was investigated on alfalfa seeds during storage and
      postgermination. Alfalfa seeds were inoculated with MNV, TV, or HAV with titers
      of 6.46 +/- 0.06 log PFU/g, 3.87 +/- 0.38 log PFU/g, or 7.01 +/- 0.07 log 50%
      tissue culture infectious doses (TCID50)/g, respectively. Inoculated seeds were
      stored for up to 50 days at 22 degrees C and sampled during that storage period
      on days 0, 2, 5, 10, and 15. Following storage, virus presence was monitored over
      a 1-week germination period. Viruses remained infectious after 50 days, with
      titers of 1.61 +/- 0.19 log PFU/g, 0.85 +/- 0.21 log PFU/g, and 3.43 +/- 0.21 log
      TCID50/g for MNV, TV, and HAV, respectively. HAV demonstrated greater persistence
      than MNV and TV, without a statistically significant reduction over 20 days (<1
      log TCID50/g); however, relatively high levels of genomic copies of all viruses
      persisted over the testing time period. Low titers of viruses were found on
      sprouts and were located in all tissues as well as in sprout-spent water sampled
      on days 1, 3, and 6 following seed planting. Results revealed the persistence of
      viruses in seeds for a prolonged period of time, and perhaps of greater
      importance these data suggest the ease of which virus may transfer from seeds to
      sprouts and spent water during germination. These findings highlight the
      importance of sanitation and prevention procedures before and during germination.

PMID- 24014538
TI  - Rapid sample processing for detection of food-borne pathogens via cross-flow
      microfiltration.
AB  - This paper reports an approach to enable rapid concentration and recovery of
      bacterial cells from aqueous chicken homogenates as a preanalytical step of
      detection. This approach includes biochemical pretreatment and prefiltration of
      food samples and development of an automated cell concentration instrument based
      on cross-flow microfiltration. A polysulfone hollow-fiber membrane module having
      a nominal pore size of 0.2 MUm constitutes the core of the cell concentration
      instrument. The aqueous chicken homogenate samples were circulated within the
      cross-flow system achieving 500- to 1,000-fold concentration of inoculated
      Salmonella enterica serovar Enteritidis and naturally occurring microbiota with
      70% recovery of viable cells as determined by plate counting and quantitative PCR
      (qPCR) within 35 to 45 min. These steps enabled 10 CFU/ml microorganisms in
      chicken homogenates or 10(2) CFU/g chicken to be quantified. Cleaning and
      sterilizing the instrument and membrane module by stepwise hydraulic and chemical
      cleaning (sodium hydroxide and ethanol) enabled reuse of the membrane 15 times
      before replacement. This approach begins to address the critical need for the
      food industry for detecting food pathogens within 6 h or less. 

PMID- 24014539
TI  - Characterization of the bacterial community of the chemically defended Hawaiian
      sacoglossan Elysia rufescens.
AB  - Sacoglossans are characterized by the ability to sequester functional
      chloroplasts from their algal diet through a process called kleptoplasty,
      enabling them to photosynthesize. The bacterial diversity associated with
      sacoglossans is not well understood. In this study, we coupled traditional
      cultivation-based methods with 454 pyrosequencing to examine the bacterial
      communities of the chemically defended Hawaiian sacoglossan Elysia rufescens and
      its secreted mucus. E. rufescens contains a defense molecule, kahalalide F, that
      is possibly of bacterial origin and is of interest because of its antifungal and
      anticancer properties. Our results showed that there is a diverse bacterial
      assemblage associated with E. rufescens and its mucus, with secreted mucus
      harboring higher bacterial richness than entire-E. rufescens samples. The most
      abundant bacterial groups affiliated with E. rufescens and its mucus are
      Mycoplasma spp. and Vibrio spp., respectively. Our analyses revealed that the
      Vibrio spp. that were highly represented in the cultivable assemblage were also
      abundant in the culture-independent community. Epifluorescence microscopy and
      matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS) were
      utilized to detect the chemical defense molecule kahalalide F on a longitudinal
      section of the sacoglossan. 

PMID- 24014540
TI  - Thermal inactivation of desiccation-adapted Salmonella spp. in aged chicken
      litter.
AB  - Thermal inactivation of desiccation-adapted Salmonella spp. in aged chicken
      litter was investigated in comparison with that in a nonadapted control to
      examine potential cross-tolerance of desiccation-adapted cells to heat treatment.
      A mixture of four Salmonella serovars was inoculated into the finished compost
      with 20, 30, 40, and 50% moisture contents for a 24-h desiccation adaptation.
      Afterwards, the compost with desiccation-adapted cells was inoculated into the
      aged chicken litter with the same moisture content for heat treatments at 70, 75,
      80, 85, and 150 degrees C. Recovery media were used to allow heat-injured cells
      to resuscitate. A 5-log reduction in the number of the desiccation-adapted cells
      in aged chicken litter with a 20% moisture content required >6, >6, ~4 to 5, and
      ~3 to 4 h of exposure at 70, 75, 80, and 85 degrees C, respectively. As a
      comparison, a 5-log reduction in the number of nonadapted control cells in the
      same chicken litter was achieved within ~1.5 to 2, ~1 to 1.5, ~0.5 to 1, and <0.5
      h at 70, 75, 80, and 85 degrees C, respectively. The exposure time required to
      obtain a 5-log reduction in the number of desiccation-adapted cells gradually
      became shorter as temperature and moisture content were increased. At 150 degrees
      C, desiccation-adapted Salmonella cells survived for 50 min in chicken litter
      with a 20% moisture content, whereas control cells were detectable by enrichment
      for only 10 min. Our results demonstrated that the thermal resistance of
      Salmonella in aged chicken litter was increased significantly when the cells were
      adapted to desiccation. This study also validated the effectiveness of thermal
      processing being used for producing chicken litter free of Salmonella
      contamination. 

PMID- 24014542
TI  - The relationships among perceived peer acceptance of sexual aggression,
      punishment certainty, and sexually aggressive behavior.
AB  - Researching the correlates of men's sexually aggressive behavior (i.e., verbal
      coercion and rape) is critical to both understanding and preventing sexual
      aggression. This study examined 120 men who completed an anonymous online
      questionnaire. The study aimed to determine the relative importance of two
      potential correlates of men's self-reported use of sexual aggression: (a)
      perceptions that male peers use and support sexual aggression and (b) perceptions
      of punishment likelihood associated with sexual aggression. Results revealed that
      perceptions of male friends' acceptance of sexual aggression were strongly
      associated with individual men's reports of using verbal coercion and rape.
      Perceptions of punishment likelihood were negatively correlated with verbal
      coercion but not with rape through intoxication and force. Implications for
      sexual aggression prevention are discussed. 

PMID- 24014541
TI  - Thermotoga lettingae can salvage cobinamide to synthesize vitamin B12.
AB  - We recently reported that the Thermotogales acquired the ability to synthesize
      vitamin B12 by acquisition of genes from two distantly related lineages, Archaea
      and Firmicutes (K. S. Swithers et al., Genome Biol. Evol. 4:730-739, 2012).
      Ancestral state reconstruction suggested that the cobinamide salvage gene cluster
      was present in the Thermotogales' most recent common ancestor. We also predicted
      that Thermotoga lettingae could not synthesize B12 de novo but could use the
      cobinamide salvage pathway to synthesize B12. In this study, these hypotheses
      were tested, and we found that Tt. lettingae did not synthesize B12 de novo but
      salvaged cobinamide. The growth rate of Tt. lettingae increased with the addition
      of B12 or cobinamide to its medium. It synthesized B12 when the medium was
      supplemented with cobinamide, and no B12 was detected in cells grown on
      cobinamide-deficient medium. Upstream of the cobinamide salvage genes is a
      putative B12 riboswitch. In other organisms, B12 riboswitches allow for higher
      transcriptional activity in the absence of B12. When Tt. lettingae was grown with
      no B12, the salvage genes were upregulated compared to cells grown with B12 or
      cobinamide. Another gene cluster with a putative B12 riboswitch upstream is the
      btuFCD ABC transporter, and it showed a transcription pattern similar to that of
      the cobinamide salvage genes. The BtuF proteins from species that can and cannot
      salvage cobinamides were shown in vitro to bind both B12 and cobinamide. These
      results suggest that Thermotogales species can use the BtuFCD transporter to
      import both B12 and cobinamide, even if they cannot salvage cobinamide. 

PMID- 24014543
TI  - European Society of Cardiology: World No-Tobacco Day.

PMID- 24014544
TI  - Pressure-driven microfluidic perfusion culture device for integrated dose
      response assays.
AB  - Cell-based assays are widely used in the various stages of drug discovery.
      Advances in microfluidic systems over the past two decades have enabled them to
      become a powerful tool for cell-based assays to achieve both reliability and high
      throughput. The interface between the micro-world and macro-world is important in
      industrial assay processes. Therefore, microfluidic cell-based assays using
      pressure-driven liquid handling are an ideal platform for integrated assays. The
      aim of this article is to review recent advancements in microfluidic cell-based
      assays focusing on a pressure-driven perfusion culture device. Here, we review
      the development of microfluidic cell-based assay devices and discuss the
      techniques involved in designing a microfluidic network, device fabrication,
      liquid and cell manipulation, and detection schemes for pressure-driven perfusion
      culture devices. Finally, we describe recent progress in semiautomatic and
      reliable pressure-driven microfluidic cell-based assays. 

PMID- 24014545
TI  - The endoplasmic reticulum is the main membrane source for biogenesis of the lytic
      vacuole in Arabidopsis.
AB  - Vacuoles are multifunctional organelles essential for the sessile lifestyle of
      plants. Despite their central functions in cell growth, storage, and
      detoxification, knowledge about mechanisms underlying their biogenesis and
      associated protein trafficking pathways remains limited. Here, we show that in
      meristematic cells of the Arabidopsis thaliana root, biogenesis of vacuoles as
      well as the trafficking of sterols and of two major tonoplast proteins, the
      vacuolar H(+)-pyrophosphatase and the vacuolar H(+)-adenosinetriphosphatase,
      occurs independently of endoplasmic reticulum (ER)-Golgi and post-Golgi
      trafficking. Instead, both pumps are found in provacuoles that structurally
      resemble autophagosomes but are not formed by the core autophagy machinery. Taken
      together, our results suggest that vacuole biogenesis and trafficking of
      tonoplast proteins and lipids can occur directly from the ER independent of Golgi
      function. 

PMID- 24014546
TI  - Copper response regulator1-dependent and -independent responses of the
      Chlamydomonas reinhardtii transcriptome to dark anoxia.
AB  - Anaerobiosis is a stress condition for aerobic organisms and requires extensive
      acclimation responses. We used RNA-Seq for a whole-genome view of the acclimation
      of Chlamydomonas reinhardtii to anoxic conditions imposed simultaneously with
      transfer to the dark. Nearly 1.4 * 10(3) genes were affected by hypoxia.
      Comparing transcript profiles from early (hypoxic) with those from late (anoxic)
      time points indicated that cells activate oxidative energy generation pathways
      before employing fermentation. Probable substrates include amino acids and fatty
      acids (FAs). Lipid profiling of the C. reinhardtii cells revealed that they
      degraded FAs but also accumulated triacylglycerols (TAGs). In contrast with N
      deprived cells, the TAGs in hypoxic cells were enriched in desaturated FAs,
      suggesting a distinct pathway for TAG accumulation. To distinguish
      transcriptional responses dependent on copper response regulator1 (CRR1), which
      is also involved in hypoxic gene regulation, we compared the transcriptomes of
      crr1 mutants and complemented strains. In crr1 mutants, ~40 genes were aberrantly
      regulated, reaffirming the importance of CRR1 for the hypoxic response, but
      indicating also the contribution of additional signaling strategies to account
      for the remaining differentially regulated transcripts. Based on transcript
      patterns and previous results, we conclude that nitric oxide-dependent signaling
      cascades operate in anoxic C. reinhardtii cells.

PMID- 24014547
TI  - Arabidopsis kinetochore null2 is an upstream component for centromeric histone H3
      variant cenH3 deposition at centromeres.
AB  - The centromeric histone H3 variant cenH3 is an essential centromeric protein
      required for assembly, maintenance, and proper function of kinetochores during
      mitosis and meiosis. We identified a kinetochore null2 (KNL2) homolog in
      Arabidopsis thaliana and uncovered features of its role in cenH3 loading at
      centromeres. We show that Arabidopsis KNL2 colocalizes with cenH3 and is
      associated with centromeres during all stages of the mitotic cell cycle, except
      from metaphase to mid-anaphase. KNL2 is regulated by the proteasome degradation
      pathway. The KNL2 promoter is mainly active in meristematic tissues, similar to
      the cenH3 promoter. A knockout mutant for KNL2 shows a reduced level of cenH3
      expression and reduced amount of cenH3 protein at chromocenters of meristematic
      nuclei, anaphase bridges during mitosis, micronuclei in pollen tetrads, and 30%
      seed abortion. Moreover, knl2 mutant plants display reduced expression of
      suppressor of variegation 3-9 homologs2, 4, and 9 and reduced DNA methylation,
      suggesting an impact of KNL2 on the epigenetic environment for centromere
      maintenance.

PMID- 24014548
TI  - Zeaxanthin binds to light-harvesting complex stress-related protein to enhance
      nonphotochemical quenching in Physcomitrella patens.
AB  - Nonphotochemical quenching (NPQ) dissipates excess energy to protect the
      photosynthetic apparatus from excess light. The moss Physcomitrella patens
      exhibits strong NPQ by both algal-type light-harvesting complex stress-related
      (LHCSR)-dependent and plant-type S subunit of Photosystem II (PSBS)-dependent
      mechanisms. In this work, we studied the dependence of NPQ reactions on
      zeaxanthin, which is synthesized under light stress by violaxanthin deepoxidase
      (VDE) from preexisting violaxanthin. We produced vde knockout (KO) plants and
      showed they underwent a dramatic reduction in thermal dissipation ability and
      enhanced photoinhibition in excess light conditions. Multiple mutants (vde lhcsr
      KO and vde psbs KO) showed that zeaxanthin had a major influence on LHCSR
      dependent NPQ, in contrast with previous reports in Chlamydomonas reinhardtii.
      The PSBS-dependent component of quenching was less dependent on zeaxanthin,
      despite the near-complete violaxanthin to zeaxanthin exchange in LHC proteins.
      Consistent with this, we provide biochemical evidence that native LHCSR protein
      binds zeaxanthin upon excess light stress. These findings suggest that zeaxanthin
      played an important role in the adaptation of modern plants to the enhanced
      levels of oxygen and excess light intensity of land environments. 

PMID- 24014550
TI  - Epicardial tumour originating from renal cell carcinoma.

PMID- 24014549
TI  - Tissue-specific profiling reveals transcriptome alterations in Arabidopsis
      mutants lacking morphological phenotypes.
AB  - Traditional genetic analysis relies on mutants with observable phenotypes.
      Mutants lacking visible abnormalities may nevertheless exhibit molecular
      differences useful for defining gene function. To examine this, we analyzed
      tissue-specific transcript profiles from Arabidopsis thaliana transcription
      factor gene mutants with known roles in root epidermis development, but lacking a
      single-gene mutant phenotype due to genetic redundancy. We discovered substantial
      transcriptional changes in each mutant, preferentially affecting root epidermal
      genes in a manner consistent with the known double mutant effects. Furthermore,
      comparing transcript profiles of single and double mutants, we observed
      remarkable variation in the sensitivity of target genes to the loss of one or
      both paralogous genes, including preferential effects on specific branches of the
      epidermal gene network, likely reflecting the pathways of paralog
      subfunctionalization during evolution. In addition, we analyzed the root
      epidermal transcriptome of the transparent testa glabra2 mutant to clarify its
      role in the network. These findings provide insight into the molecular basis of
      genetic redundancy and duplicate gene diversification at the level of a specific
      gene regulatory network, and they demonstrate the usefulness of tissue-specific
      transcript profiling to define gene function in mutants lacking informative
      visible changes in phenotype. 

PMID- 24014551
TI  - Preliminary study of efficacy of dynamic compression system in the correction of
      typical pectus carinatum.
AB  - OBJECTIVES: This preliminary study evaluates, by qualitative score, the efficacy
      of the dynamic compression system (DCS) with a pressure-measuring device in the
      treatment of pectus carinatum (PC) as an alternative to surgery. METHODS: A total
      of 68 patients (infants, adolescents and young adults) presenting with typical PC
      (64 males and 4 females) were evaluated in our Chest Wall Deformities Unit,
      between October 2011 and February 2013. The criteria for including subjects were:
      patients with typical condrogladiolar PC and pressure for initial correction
      (PIC) <= 9 PSI (pound square inch). Seven patients were excluded in this study:
      three typical PC were treated by minimal invasive surgery (Abramson technique)
      due to highly elevated PIC and four atypical PC, hybrids forms (PE and PC) were
      treated by cup suction for pectus excavatum and by the DCS for the PC. The
      management protocol included: adjustment of the DCS, strengthening exercises and
      monthly clinical follow-up. The partial and final results were evaluated by the
      patients, by their parents or by both, using a qualitative scoring scale that was
      measured in a three-step grading system, where C is a low or very low result, B
      is acceptable and A is a very good or excellent result. RESULTS: A total of 61
      patients (59 males and 2 females) presenting with typical PC were treated by the
      DCS and included: symmetric PC in 43 cases and asymmetric PC in 18 cases. The
      mean age was 13.5 years (5-25). The mean PIC was 6.3 PSI (3-9 PSI). The mean
      utilization time was 19 h daily. The patients were divided into three groups. In
      Group I, consisting of 35 cases, all the patients have already completed the
      treatment with excellent aesthetic results (A). In 12 cases, Group II, the normal
      shape of the thorax has been obtained; all the patients in this group rated their
      results as excellent (A); however, these patients are still wearing the brace as
      a retainer for 3 additional months. Fourteen patients, Group III, are progressing
      and improving under active treatment, and surgeons and patients are very
      satisfied with the initial results. None of the 61 patients in this study
      abandoned the treatment and no complications were found. CONCLUSIONS: This
      preliminary study demonstrated that the DCS with a pressure-measuring device is a
      minimal invasive system effective for treatment of PC in patients where the
      anterior chest wall is still compliant. The control of different pressure
      measurements could be used as the inclusion criterion as well as a predictive
      factor for aesthetic results and treatment duration.

PMID- 24014552
TI  - Physical education issues for students with autism: school nurse challenges.
AB  - Extant studies indicate persons with autism have difficulties in social
      interaction, verbal and nonverbal communication, repetitive behaviors, and poor
      ability to generalize learned skills. Obesity has also been identified as
      significantly affecting children with autism spectrum disorders (ASD). Negative
      experience in physical education (PE) may be the antecedent behavior to lack of
      activities that are mediators to sedentary lifestyles and contributors to the
      chronic illnesses associated with overweight and obesity. Students with ASD often
      cannot perform required activities to meet required PE standards. It is
      imperative school nurses be aware of the many challenges students with ASD bring
      into a PE class. School nurses provide education for the members of the school
      community, including the Individualized Education Plan team, regarding the need
      for attention to limitations, including physical activity, of students with ASD. 

PMID- 24014553
TI  - Addison's disease: a survey on 633 patients in Padova.
AB  - OBJECTIVE: Addison's disease (AD) is a rare endocrine condition. DESIGN: We aimed
      to evaluate clinical, immunologic, adrenal imaging, and genetic features in 633
      Italian patients with AD followed up since 1967. METHODS: Adrenal cortex
      autoantibodies, presence of other autoimmune and nonautoimmune diseases,
      nonadrenal autoantibodies, adrenal imaging, and genetic profile for HLA-DRB1 and
      AIRE were analyzed. RESULTS: A total of 492 (77.7%) patients were found to be
      affected by autoimmune AD (A-AD), 57 (9%) tuberculous AD, 29 (4.6%) genetic
      associated AD, 10 (1.6%) adrenal cancer, six (0.94%) post-surgical AD, four
      (0.6%) vascular disorder-related AD, three (0.5%) post-infectious AD, and 32
      (5.1%) were defined as idiopathic. Adrenal cortex antibodies were detected in the
      vast majority (88100%) of patients with recent onset A-AD, but in none of those
      with nonautoimmune AD. Adrenal imaging revealed normal/atrophic glands in all A
      AD patients: 88% of patients with A-AD had other clinical or subclinical
      autoimmune diseases or were positive for nonadrenal autoantibodies. Based on the
      coexistence of other autoimmune disorders, 65.6% of patients with A-AD were found
      to have type 2 autoimmune polyendocrine syndrome (APS2), 14.4% have APS1, and
      8.5% have APS4. Class II HLA alleles DRB1*03 and DRB1*04 were increased, and
      DRB1*01, DRB1*07, DRB1*013 were reduced in APS2 patients when compared with
      controls. Of the patients with APS1, 96% were revealed to have AIRE gene
      mutations. CONCLUSIONS: A-AD is the most prevalent form of adrenal insufficiency
      in Italy, and ~90% of the patients are adrenal autoantibody-positive at the
      onset. Assessment of patients with A-AD for the presence of other autoimmune
      diseases should be helpful in monitoring and diagnosing APS types 1, 2, or 4 and
      improving patients' care.

PMID- 24014555
TI  - Eosinophilic cystitis: treatment with intravesical steroids and oral
      antihistamines.
AB  - This is a case of eosinophilic cystitis in a 56-year-old indigenous Australian
      woman who presented with urosepsis on the background of a urinary tract infection
      unresponsive to oral antibiotics. After resolution of the urosepsis, she had
      persisting urinary retention and a cystoscopy/bladder biopsy suggested
      eosinophilic cystitis. After 1 month of intravesical hydrocortisone and oral
      loratadine, repeat cystoscopy showed vast improvement in the bladder lesions.
      This case further strengthens the use of intravesical steroids and oral
      antihistamines for the management of eosinophilic cystitis.

PMID- 24014554
TI  - Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and
      combined iron chelators as an ideal therapy.
AB  - OBJECTIVE: Endocrine complications characterised patients with beta thalassaemia
      (betaT). In particular, thyroid dysfunction occurs frequently in betaT major, but
      its long-term natural history is poorly understood. DESIGN: A total of 72 betaT
      patients were followed for 8 years. The incidence of thyreopathies, defined as
      the primary study endpoint, was assessed. The aim of this study was to analyse
      the prognostic role of ferritin for thyreopathies in patients with major and
      intermedia betaT. The power of different iron chelators to treat iron overload
      and to prevent or reverse thyreopathies was also assessed. METHODS: Patients were
      treated with chelators with different chelation strategies during the study.
      Receiver operating characteristics analysis was employed to calculate the area
      under the curve for serum ferritin to find the best cutoff values capable of
      identifying thyroid dysfunction in thalassaemic patients. Kaplan-Meier curves
      were generated to assess incidence of thyreopathy. Adjusted risk estimates for
      thyreopathy were calculated using univariate followed by multivariate Cox
      proportional hazard regression analysis. RESULTS: PATIENTS WITH THYROID
      DYSFUNCTION WERE CHARACTERISED BY HIGHER FERRITIN WHEN COMPARED WITH PATIENTS
      WITHOUT THYREOPATHIES (1500 (8722336) VS 513 (370698) G/L; P0.0001). PATIENTS
      WITH FERRITIN VALUES ABOVE 1800G/L EXPERIENCED A SIGNIFICANTLY FASTER EVOLUTION
      TO ENDPOINT (LOG-RANK ((2)): 7.7; P=0.005). Ferritin predicted high risk of
      thyroid dysfunction independently of confounding factors (hazard ratio: 1.20;
      P<0.0001). The intensification of chelation therapy led to an amelioration of
      thyroid function. CONCLUSIONS: Ferritin represents a prognostic marker for betaT
      patients and a predictive factor for progression to thyroid dysfunction.
      Intensive chelation therapy allows the prevention and reversibility of thyroid
      complications.

PMID- 24014556
TI  - Relieving the burden: palliative centesis of an oedematous scrotal wall due to
      anasarca in end-stage heart failure.
AB  - End-stage congestive heart failure is a leading diagnosis among hospice patients
      without cancer. As in terminally ill cancer patients; the aim of the treatment
      was to focus on palliation and maximum symptom relief. Anasarca, a widespread
      swelling of the skin because of effusion of fluid into the extracellular space,
      is a common sign in end-stage heart failure causing much pain and discomfort. We
      described a simple, safe, bed-side technique to alleviate the discomfort
      associated with massive scrotal oedema.

PMID- 24014557
TI  - Osler's nodes, Janeway lesions and splinter haemorrhages.

PMID- 24014558
TI  - A novel treatment for management of a trapped placenta using intracervical
      nitroglycerin tablets.
AB  - A 34-year-old gravida 2, para 1 woman delivered a viable male infant and
      developed retained placenta due to entrapment. A nitroglycerin tablet was used to
      relax the lower uterine segment and cervix, which allowed the placenta to pass
      through the cervix for delivery. The nitroglycerin tablet was placed in the
      cervix and held in place by the delivering physician as it dissolved. Soon after
      administration, the intact placenta delivered. The patient did not experience the
      typical side effects of headache, asymptomatic decrease in blood pressure,
      hypotension, palpitations or dizziness that can be associated with administration
      of nitroglycerin. We suspect that this novel localised route of nitroglycerin
      administration may be an effective management strategy to treat trapped placenta
      while minimising side effects. However, the outcomes of this treatment would
      require further study.

PMID- 24014559
TI  - Bilateral auricular classic Kaposi's sarcoma.
AB  - In 2009, a 57-year-old man was referred to our maxillo facial surgery department
      for the appearance of a reddish-purplish swelling on his right helix. The lesion
      was more than 1 cm in length and did not show changes for 3 months. He was
      otherwise healthy, without any predisposing factors. The patient denied smoking,
      alcohol misuse and intravenous drug use. He had no family history of similar
      lesions or Kaposi's sarcoma . The lesion was completely excised and the surgical
      defect reconstructed with a local flap. In 2011 the same patient returned to our
      attention because of the appearance of a new lesion, similar to the first one on
      the other auricle. The lesion was completely removed. The same situation recurred
      in September 2012, when the patient presented a new little reddish-purplish
      swelling of 3 mm on the left helix. The lesion was excised. The patient has not
      reported further lesion at present.

PMID- 24014560
TI  - Herpes zoster mandibularis.

PMID- 24014561
TI  - Complex partial status epilepticus in a patient with Crohn's disease.
AB  - Few cases of Crohn's disease complicated with meningitis and epidural abscess
      have been described in literature. We present a case of a 42-year-old former
      smoker female patient diagnosed with Crohn's disease in September 1995 (with
      severe nutritional problems). On 20 February 2012, she was admitted due to a
      probable sepsis (without any previous treatment). After several days she
      developed a confusion syndrome (probable Wernicke's disease). On 5 March 2012,
      the patient presented with a febrile episode of 39  degrees  C. Two days later,
      the patient presented aphasia and paraparesis, and 3 days later she presented a
      complex partial status epilepticus. A lumbar puncture was performed and showed
      131 leucocytes (63% granulocytes) and proteins 296.3. The abdominopelvic CT scan
      revealed a presacral collection that seem to extend cranially towards the
      lumbosacral spine. The lumbar MRI confirmed the lumbar epidural abscess secondary
      to the fistulisation of the presacral abscess.

PMID- 24014562
TI  - Toxic shock syndrome related to Streptococcus equi subsp zooepidemicus.
AB  - We describe a documented streptococcal toxic shock syndrome linked to horse-to
      man transmission of Streptococcus equi subsp zooepidemicus. The patient was
      treated successfully with respiratory and haemodynamic support in conjunction
      with antibiotic treatment associated with polyvalent human immunoglobulin and
      high-volume venovenous haemofiltration.

PMID- 24014563
TI  - Coexistence of seizure episodes and symptomatic sinoatrial arrest occurring in
      two sisters suggests an underlying cardioneuronal channelopathy.

PMID- 24014564
TI  - A compound odontoma in the path of an erupting incisor.

PMID- 24014565
TI  - The case of the missing wrist: a probable case of idiopathic osteolysis.

PMID- 24014566
TI  - A bizarre object to swallow.

PMID- 24014567
TI  - A redundant epistatic interaction between IRF5 and STAT4 of the type I interferon
      pathway in susceptibility to lupus and rheumatoid arthritis.
AB  - OBJECTIVE: Two transcription factors in the type I interferon pathway, IRF5 and
      STAT4, have been genetically associated with susceptibility to both systemic
      lupus erythematosus (SLE) and rheumatoid arthritis (RA). This study aimed to
      determine whether these two genes interact with each other to affect the disease
      susceptibilities. METHODS: The genetic interactions between IRF5 and STAT4
      polymorphisms in SLE and RA susceptibility were examined using the epistasis
      options in PLINK software. This study analyzes the genetic data from 2558
      unrelated Korean participants including 589 SLE patients, 987 RA patients, and
      982 controls. RESULTS: All 12 polymorphisms were individually associated with SLE
      susceptibility (p = 2.49 * 10(-8) to 0.00360). Among the three SLE-associated
      polymorphisms of IRF5, rs77571059, alternatively called CGGGG(3-4) indel,
      exhibited the lowest p value (4.60 * 10(-5)) and accounted for the observed
      associations of the other two single-nucleotide polymorphisms (SNPs). Among the
      nine SLE-associated SNPs of STAT4, rs16833215 exhibited the lowest p value (2.49
      * 10(-8)) and accounted for all the other associations. These two polymorphisms,
      rs77571059 of IRF5 and rs16833215 of STAT4, interacted with each other for SLE
      susceptibility in a redundant manner (ORinteraction = 0.77, P epistasis = 0.040).
      Furthermore, these two polymorphisms, which had been individually associated with
      RA susceptibility, also interacted for RA susceptibility in the same manner
      (ORinteraction = 0.75, P epistasis = 0.014). CONCLUSIONS: A redundant interaction
      between IRF5 and STAT4 polymorphisms was found in susceptibility to the type I
      interferon pathway-associated rheumatic autoimmune diseases, SLE and RA, calling
      for further studies on confirmation of these findings.

PMID- 24014568
TI  - Decoy cells due to polyomavirus BK infection in the urine sediment of a patient
      with lupus nephritis.

PMID- 24014569
TI  - Successful treatment of a mycophenolate mofetil-refractory proliferative lupus
      nephritis with Belimumab in a 19-year-old woman.
AB  - We report the case of a 19-year-old woman with progressive proliferative lupus
      nephritis (LN) class III after induction and maintenance therapy with
      mycophenolate mofetil (MMF). Despite a satisfying clinical improvement
      proteinuria progressed under this medication. We treated the patient with
      additional belimumab after discussing other options. Following treatment with
      belimumab, proteinuria rapidly improved to almost normal levels and clinical
      remission lasted. Belimumab might hold promise for this indication. 

PMID- 24014570
TI  - Rituximab therapy in refractory macrophage activation syndrome secondary to
      systemic lupus erythematosus.

PMID- 24014571
TI  - Myocarditis along with acute ischaemic cerebellar, pontine and lacunar infarction
      following viper bite.
AB  - Cerebrovascular complications are rare following viper bites. A 65-year-old man
      presented with loss of consciousness and developed haemiparesis following a viper
      bite. Coagulation parameters were severely deranged. MRI showed acute ischaemic
      infarction on the left side in the precentral and postcentral gyrus, hemipons and
      cerebellum. Troponin T was elevated and transient left bundle branch block was
      seen. The patient had a good outcome following treatment with Anti Snake Venom
      and supportive therapy. Possible mechanisms of infarction are discussed. 

PMID- 24014573
TI  - Impact of electroviscosity on the hydraulic conductance of the bordered pit
      membrane: a theoretical investigation.
AB  - In perfusion experiments, the hydraulic conductance of stem segments ( ) responds
      to changes in the properties of the perfusate, such as the ionic strength ( ),
      pH, and cationic identity. We review the experimental and theoretical work on
      this phenomenon. We then proceed to explore the hypothesis that electrokinetic
      effects in the bordered pit membrane (BPM) contribute to this response. In
      particular, we develop a model based on electroviscosity in which hydraulic
      conductance of an electrically charged porous membrane varies with the properties
      of the electrolyte. We use standard electrokinetic theory, coupled with
      measurements of electrokinetic properties of plant materials from the literature,
      to determine how the conductance of BPMs, and therefore , may change due to
      electroviscosity. We predict a nonmonotonic variation of with with a maximum
      reduction of 18%. We explore how this reduction depends on the characteristics of
      the sap and features of the BPM, such as pore size, density of chargeable sites,
      and their dissociation constant. Our predictions are consistent with changes in
      observed for physiological values of sap and pH. We conclude that
      electroviscosity is likely responsible, at least partially, for the electrolyte
      dependence of conductance through pits and that electroviscosity may be strong
      enough to play an important role in other transport processes in xylem. We
      conclude by proposing experiments to differentiate the impact of electroviscosity
      on from that of other proposed mechanisms. 

PMID- 24014572
TI  - Observational case-control study of the prevalence of chronic cerebrospinal
      venous insufficiency in multiple sclerosis: results from the CoSMo study.
AB  - BACKGROUND: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed
      as a possible cause of multiple sclerosis (MS). OBJECTIVES: The CoSMo study
      evaluated the association between CCSVI and MS. METHODS: The primary end-point of
      this multicentric, case-control study was to compare the prevalence of CCSVI
      between patients with MS, patients with other neurodegenerative diseases (ONDs)
      and healthy controls (HCs). Color-coded duplex sonography was performed by a
      sonologist and the images were sent to one of three central sonologists for a
      second reading. Agreement between local and central sonologists or, in case of
      disagreement, the predominant judgment among the three central readers, was
      required for a diagnosis of CCSVI. All readings, data collection and analysis
      were blinded. RESULTS: The study involved 35 MS centers across Italy and included
      1874 subjects aged 18-55. 1767 (94%) were evaluable: 1165 MS patients, 226
      patients with ONDs and 376 HCs. CCSVI prevalence was 3.26%, 3.10% and 2.13% for
      the MS, OND and HC groups, respectively. No significant difference in CCSVI
      prevalence was found amongst the three cohorts (MS versus HC, OR = 1.55, 95%CI =
      0.72-3.36, p = 0.30; OND versus HC, OR = 1.47, 95%CI = 0.53-4.11, p = 0.46; MS
      versus OND, OR = 1.05, 95%CI = 0.47-2.39, p = 0.99). High negative and low
      positive agreement was found between the local and centralized readers.
      CONCLUSIONS: CCSVI is not associated with MS.

PMID- 24014574
TI  - Dissection of tomato lycopene biosynthesis through virus-induced gene silencing.
AB  - Lycopene biosynthesis in tomato (Solanum lycopersicum) fruits has been proposed
      to proceed through a poly-cis pathway catalyzed by phytoene synthase (PSY), two
      desaturases (phytoene desaturase [PDS] and zeta-carotene desaturase [ZDS]), and
      two cis-trans isomerases (zeta-carotene isomerase [ZISO] and prolycopene
      isomerase [CrtISO]). The mechanism of action of these enzymes has been studied in
      Escherichia coli, but a systematic study of their in vivo function is lacking. We
      studied the function of nine candidate genes (PSY1, PSY2, PSY3, PDS, ZDS, ZISO,
      CrtISO, CrtISO-Like1, and CrtISO-Like2) using virus-induced gene silencing (VIGS)
      coupled to high-resolution liquid chromatography coupled with diode array
      detector and mass spectrometry, which allowed the identification and quantitation
      of 45 different carotenoid isomers, including linear xanthophylls. The data
      confirm the confinement of the VIGS signal to the silenced fruits and the
      similarity of the phenotypes of PSY1- and CrtISO-silenced fruits with those of
      the yellow flesh and tangerine mutants. Light was able to restore lycopene
      biosynthesis in ZISO-silenced fruits. Isomeric composition of fruits silenced at
      different metabolic steps suggested the existence of three functional units,
      comprising PSY1, PDS/ZISO, and ZDS/CrtISO, and responsible for the synthesis of
      15-cis-phytoene, 9,9'-di-cis-zeta-carotene, and all-trans-lycopene, respectively.
      Silencing of a desaturase (PDS or ZDS) resulted in the induction of the isomerase
      in the same functional unit (ZISO or CrtISO, respectively). All-trans-zeta
      carotene was detectable in nonsilenced fruits, greatly increased in ZDS-silenced
      ones, and disappeared in CrtISO-Like1-/CrtISO-Like2-silenced ones, suggesting the
      existence of a metabolic side branch, comprising this compound and initiated by
      the latter enzymes. 

PMID- 24014575
TI  - Phytochrome C is a key factor controlling long-day flowering in barley.
AB  - The spring-type near isogenic line (NIL) of the winter-type barley (Hordeum
      vulgare ssp. vulgare) var. Hayakiso 2 (HK2) was developed by introducing
      VERNALIZATION-H1 (Vrn-H1) for spring growth habit from the spring-type var. Indo
      Omugi. Contrary to expectations, the spring-type NIL flowered later than winter
      type HK2. This phenotypic difference was controlled by a single gene, which
      cosegregated only with phytochrome C (HvPhyC) among three candidates around the
      Vrn-H1 region (Vrn-H1, HvPhyC, and CASEIN KINASE IIalpha), indicating that HvPhyC
      was the most likely candidate gene. Compared with the late-flowering allele
      HvPhyC-l from the NIL, the early-flowering allele HvPhyC-e from HK2 had a single
      nucleotide polymorphism T1139C in exon 1, which caused a nonsynonymous amino acid
      substitution of phenylalanine at position 380 by serine in the functionally
      essential GAF (3', 5'-cyclic-GMP phosphodiesterase, adenylate cyclase, formate
      hydrogen lyase activator protein) domain. Functional assay using a rice (Oryza
      sativa) phyA phyC double mutant line showed that both of the HvPhyC alleles are
      functional, but HvPhyC-e may have a hyperfunction. Expression analysis using NILs
      carrying HvPhyC-e and HvPhyC-l (NIL [HvPhyC-e] and NIL [HvPhyC-l], respectively)
      showed that HvPhyC-e up-regulated only the flowering promoter FLOWERING LOCUS T1
      by bypassing the circadian clock genes and flowering integrator CONSTANS1 under a
      long photoperiod. Consistent with the up-regulation, NIL (HvPhyC-e) flowered
      earlier than NIL (HvPhyC-l) under long photoperiods. These results implied that
      HvPhyC is a key factor to control long-day flowering directly. 

PMID- 24014577
TI  - Fertilization and uniparental chromosome elimination during crosses with maize
      haploid inducers.
AB  - Producing maternal haploids via a male inducer can greatly accelerate maize (Zea
      mays) breeding process. However, the mechanism underlying haploid formation
      remains unclear. In this study, we constructed two inducer lines containing
      cytogenetic marker B chromosome or alien centromeric histone H3 variant-yellow
      fluorescent protein vector to investigate the mechanism. The two inducer lines as
      the pollinators were crossed with a hybrid ZhengDan958. B chromosomes were
      detected in F1 haploids at a low frequency, which was direct evidence to support
      the occurrence of selective chromosome elimination during haploid formation. We
      found that most of the inducer chromosomes were eliminated in haploid embryonic
      cells during the first week after pollination. The gradual elimination of
      chromosomes was also detected in the endosperm of defective kernels, although it
      occurred only in some endosperm cells as late as 15 d after pollination. We also
      performed a genome-wide identification of single nucleotide polymorphism markers
      in the inducers, noninducer inbred lines, and 42 derived haploids using a 50K
      single nucleotide polymorphism array. We found that an approximately 44-Mb
      heterozygous fragment from the male parent was detected in a single haploid,
      which further supported the occurrence of paternal introgression. Our results
      suggest that selective elimination of uniparental chromosomes leads to the
      formation of haploid and possible defective kernels in maize as well, which is
      accompanied with unusual paternal introgression in haploid cells. 

PMID- 24014576
TI  - Recent advances in calcium/calmodulin-mediated signaling with an emphasis on
      plant-microbe interactions.

PMID- 24014578
TI  - Alterations in seed development gene expression affect size and oil content of
      Arabidopsis seeds.
AB  - Seed endosperm development in Arabidopsis (Arabidopsis thaliana) is under control
      of the polycomb group complex, which includes Fertilization Independent Endosperm
      (FIE). The polycomb group complex regulates downstream factors, e.g. Pheres1
      (PHE1), by genomic imprinting. In heterozygous fie mutants, an endosperm develops
      in ovules carrying a maternal fie allele without fertilization, finally leading
      to abortion. Another endosperm development pathway depends on MINISEED3 (a WRKY10
      transcription factor) and HAIKU2 (a leucine-rich repeat kinase). While the role
      of seed development genes in the embryo and endosperm establishment has been
      studied in detail, their impact on metabolism and oil accumulation remained
      unclear. Analysis of oil, protein, and sucrose accumulation in mutants and
      overexpression plants of the four seed development genes revealed that (1) seeds
      carrying a maternal fie allele accumulate low oil with an altered composition of
      triacylglycerol molecular species; (2) homozygous mutant seeds of phe1, mini3,
      and iku2, which are smaller, accumulate less oil and slightly less protein, and
      starch, which accumulates early during seed development, remains elevated in
      mutant seeds; (3) embryo-specific overexpression of FIE, PHE1, and MINI3 has no
      influence on seed size and weight, nor on oil, protein, or sucrose content; and
      (4) overexpression of IKU2 results in seeds with increased size and weight, and
      oil content of overexpressed IKU2 seeds is increased by 35%. Thus, IKU2
      overexpression represents a novel strategy for the genetic manipulation of the
      oil content in seeds. 

PMID- 24014580
TI  - Aneurysmal bone cyst of temporal bone.
AB  - Aneurysmal bone cysts (ABC) are benign neoplasms frequently occurring in the long
      tubular bones. It is very rare in temporal bone. We report a case of ABC of the
      left temporal bone in an 8-year-old Asian boy who presented clinically with
      swelling over the left temporal region for 5 months. CT and MRI features were
      suggestive of ABC. Surgical resection was performed and on follow-up the patient
      was doing well. CT and MRI are the imaging modalities for proper evaluation of
      ABC, aiding to diagnosis and helpful in treatment planning.

PMID- 24014579
TI  - Calcium-dependent protein kinases: hubs in plant stress signaling and
      development.

PMID- 24014581
TI  - Bilateral femoral fractures in a 21-year-old man following a simple fall.
AB  - We present a case of a 21-year-old man with hip pain to the orthopaedic team.
      During the initial assessment he was found to be hypercalcaemic (adjusted calcium
      3.55) due to the primary hyperparathoidism (PTH 1285), with all other screening
      for multiple endocrine neoplasia negative. During his time on the ward while
      being treated for the hypercalcaemia he had a fall resulting in bilateral femoral
      fractures, requiring surgical management. He underwent an emergency exploration
      of neck and excision of a large parathyroid adenoma, measuring 5.5 cm. He also
      developed renal failure as a result of nephrocalcinosis. This case highlights the
      importance of early detection and management of hyperparathyroidism with the aim
      of preventing long-term complications. This patient ultimately required a renal
      transplant and multiple orthopaedic procedures as a result of undiagnosed PTH and
      recently underwent excision of the remaining parathyroid glands.

PMID- 24014582
TI  - Progressive external ophthalmoplegia (PEO) due to a mutation in the C10orf2
      (PEO1) gene mimicking a myasthenic crisis.
AB  - We described a case of a patient with autosomal dominant progressive external
      ophthalmoplegia (PEO) who presented with the acute onset dysphagia,
      quadriparesis, ptosis and respiratory insufficiency following a cardiac procedure
      and mimicking a myasthenic crisis. A pathogenic mutation in the C10orf2 (PEO1)
      gene was confirmed. The unusual presentation of our patient contributes to expand
      the clinical phenotype of PEO1 mutations and reinforces the need to consider
      mitochondrial myopathy as differential diagnosis of myasthenia gravis even in the
      case of acute onset symptoms.

PMID- 24014583
TI  - The cold-fingered carpenter: an uncommon cause of digital ischaemia.

PMID- 24014584
TI  - Giant intracranial calcification associated with new onset focal seizure.

PMID- 24014585
TI  - Bilateral optic neuropathy in a patient with familial amyloidotic polyneuropathy.
AB  - Amyloidogenic transthyretin (ATTR)-related familial amyloidotic polyneuropathy
      (FAP) is an autosomal-dominant hereditary disease characterised by slowly
      progressive peripheral sensorimotor and autonomic neuropathy and tissue
      involvement of the heart, kidneys and central nervous system. Secondary glaucoma
      has been reported following intraocular surgery, but optic nerve involvement
      unrelated to glaucoma has not previously been described. We reported a male
      patient in his late 40s when deceased, who previously had a liver transplant in
      order to reduce the abnormal protein synthesis underlying his FAP ATTR Val30Met
      mutation. After 11 years of ophthalmic follow-up best-corrected visual acuity was
      20/100 in his seeing eye, which further had visual field findings suggestive of
      optic neuropathy. This was also the diagnosis underlying the preceding insidious
      full loss of vision in the fellow eye, with colour Doppler imaging to support an
      ischaemic aetiology. To our knowledge, this is the first report of ischaemic
      optic neuropathy in this familial amyloid disorder.

PMID- 24014586
TI  - Hutch diverticulum presenting as acute urinary retention in early life.
AB  - There are only a few reports of recurrent acute urinary retention caused by
      obstruction from congenital paraureteral diverticulum. We review the literature
      and present a case of a 14-month-old boy with bilateral hutch diverticuli who had
      his first episode of acute urinary retention in the neonatal period caused by
      left-sided diverticulum. We emphasised the fact that hutch diverticulum should be
      considered as one of the possible differential diagnoses in a child presenting
      with acute urinary retention.

PMID- 24014588
TI  - Weighted means and Karcher equations of positive operators.
AB  - The Karcher or least-squares mean has recently become an important tool for the
      averaging and study of positive definite matrices. In this paper, we show that
      this mean extends, in its general weighted form, to the infinite-dimensional
      setting of positive operators on a Hilbert space and retains most of its
      attractive properties. The primary extension is via its characterization as the
      unique solution of the corresponding Karcher equation. We also introduce power
      means in the infinite-dimensional setting and show that the Karcher mean is the
      strong limit of the monotonically decreasing family of power means as . We show
      each of these characterizations provide important insights about the Karcher
      mean. 

PMID- 24014587
TI  - Primate genome architecture influences structural variation mechanisms and
      functional consequences.
AB  - Although nucleotide resolution maps of genomic structural variants (SVs) have
      provided insights into the origin and impact of phenotypic diversity in humans,
      comparable maps in nonhuman primates have thus far been lacking. Using massively
      parallel DNA sequencing, we constructed fine-resolution genomic structural
      variation maps in five chimpanzees, five orang-utans, and five rhesus macaques.
      The SV maps, which are comprised of thousands of deletions, duplications, and
      mobile element insertions, revealed a high activity of retrotransposition in
      macaques compared with great apes. By comparison, nonallelic homologous
      recombination is specifically active in the great apes, which is correlated with
      architectural differences between the genomes of great apes and macaque.
      Transcriptome analyses across nonhuman primates and humans revealed effects of
      species-specific whole-gene duplication on gene expression. We identified 13 gene
      duplications coinciding with the species-specific gain of tissue-specific gene
      expression in keeping with a role of gene duplication in the promotion of
      diversification and the acquisition of unique functions. Differences in the
      present day activity of SV formation mechanisms that our study revealed may
      contribute to ongoing diversification and adaptation of great ape and Old World
      monkey lineages. 

PMID- 24014589
TI  - Nuclear quantum effects and hydrogen bond fluctuations in water.
AB  - The hydrogen bond (HB) is central to our understanding of the properties of
      water. However, despite intense theoretical and experimental study, it continues
      to hold some surprises. Here, we show from an analysis of ab initio simulations
      that take proper account of nuclear quantum effects that the hydrogen-bonded
      protons in liquid water experience significant excursions in the direction of the
      acceptor oxygen atoms. This generates a small but nonnegligible fraction of
      transient autoprotolysis events that are not seen in simulations with classical
      nuclei. These events are associated with major rearrangements of the electronic
      density, as revealed by an analysis of the computed Wannier centers and (1)H
      chemical shifts. We also show that the quantum fluctuations exhibit significant
      correlations across neighboring HBs, consistent with an ephemeral shuttling of
      protons along water wires. We end by suggesting possible implications for our
      understanding of how perturbations (solvated ions, interfaces, and confinement)
      might affect the HB network in water. 

PMID- 24014590
TI  - Observational evidence supports the role of tropical cyclones in regulating
      climate.

PMID- 24014591
TI  - Efficient nonmeiotic allele introgression in livestock using custom
      endonucleases.
AB  - We have expanded the livestock gene editing toolbox to include transcription
      activator-like (TAL) effector nuclease (TALEN)- and clustered regularly
      interspaced short palindromic repeats (CRISPR)/Cas9-stimulated homology-directed
      repair (HDR) using plasmid, rAAV, and oligonucleotide templates. Toward the
      genetic dehorning of dairy cattle, we introgressed a bovine POLLED allele into
      horned bull fibroblasts. Single nucleotide alterations or small indels were
      introduced into 14 additional genes in pig, goat, and cattle fibroblasts using
      TALEN mRNA and oligonucleotide transfection with efficiencies of 10-50% in
      populations. Several of the chosen edits mimic naturally occurring performance
      enhancing or disease- resistance alleles, including alteration of single base
      pairs. Up to 70% of the fibroblast colonies propagated without selection harbored
      the intended edits, of which more than one-half were homozygous. Edited
      fibroblasts were used to generate pigs with knockout alleles in the DAZL and APC
      genes to model infertility and colon cancer. Our methods enable unprecedented
      meiosis-free intraspecific and interspecific introgression of select alleles in
      livestock for agricultural and biomedical applications. 

PMID- 24014592
TI  - Adaptive hydrophobic and hydrophilic interactions of mussel foot proteins with
      organic thin films.
AB  - The adhesion of mussel foot proteins (Mfps) to a variety of specially engineered
      mineral and metal oxide surfaces has previously been investigated extensively,
      but the relevance of these studies to adhesion in biological environments remains
      unknown. Most solid surfaces exposed to seawater or physiological fluids become
      fouled by organic conditioning films and biofilms within minutes. Understanding
      the binding mechanisms of Mfps to organic films with known chemical and physical
      properties therefore is of considerable theoretical and practical interest. Using
      self-assembled monolayers (SAMs) on atomically smooth gold substrates and the
      surface forces apparatus, we explored the force-distance profiles and adhesion
      energies of three different Mfps, Mfp-1, Mfp-3, and Mfp-5, on (i) hydrophobic
      methyl (CH3)- and (ii) hydrophilic alcohol (OH)-terminated SAM surfaces between
      pH 3 and pH 7.5. At acidic pH, all three Mfps adhered strongly to the CH3
      terminated SAM surfaces via hydrophobic interactions (range of adhesive
      interaction energy = -4 to -9 mJ/m(2)) but only weakly to the OH-terminated SAM
      surfaces through H- bonding (adhesive interaction energy <= -0.5 mJ/m(2)). 3, 4
      Dihydroxyphenylalanine (Dopa) residues in Mfps mediate binding to both SAM
      surface types but do so through different interactions: typical bidentate H
      bonding by Dopa is frustrated by the longer spacing of OH-SAMs; in contrast, on
      CH3-SAMs, Dopa in synergy with other nonpolar residues partitions to the
      hydrophobic surface. Asymmetry in the distribution of hydrophobic residues in
      intrinsically unstructured proteins, the distortion of bond geometry between H
      bonding surfaces, and the manipulation of physisorbed binding lifetimes represent
      important concepts for the design of adhesive and nonfouling surfaces. 

PMID- 24014593
TI  - A variant CRISPR-Cas9 system adds versatility to genome engineering.

PMID- 24014594
TI  - Circular RNA and miR-7 in cancer.
AB  - MicroRNAs (miRNA) play important roles in fine-tuning gene expression and are
      often deregulated in cancer. The identification of competing endogenous RNA and
      circular RNA (circRNA) as important regulators of miRNA activity underscores the
      increasing complexity of ncRNA-mediated regulatory networks. Particularly, the
      recently identified circular RNA, ciRS-7, which acts as a designated miR-7
      inhibitor/sponge, has conceptually changed the mechanistic understanding of miRNA
      networks. As miR-7 modulates the expression of several oncogenes, disclosing the
      regulation of miR-7 activity will likely advance the understanding of various
      cancer etiologies. Here, we review the current knowledge about the ciRS-7/miR-7
      axis in cancer-related pathways and discuss possible models explaining the
      relevance of coexpressing miR-7 along with a circRNA inhibitor.

PMID- 24014596
TI  - Antitumor immunity: easy as 1, 2, 3 with monoclonal bispecific trifunctional
      antibodies?
AB  - Monoclonal antibodies occupy an increasing niche in the arsenal available to
      treat cancer. Several developments have rendered this the fastest growing sector
      in the pharmaceutical industry. Traditionally, antibodies were developed to block
      key signaling molecules implicated in tumor progression. However, antibodies also
      recruit additional immune effector mechanisms against tumors, a property that may
      be exploited for clinical benefit. Bispecific antibodies represent one such
      strategy in which elements derived from two monoclonal antibodies are
      incorporated into a single molecular species. Commonly, the bispecific approach
      is used to achieve simultaneous cross-linking of CD3 and a tumor antigen such as
      epithelial cell adhesion molecule (EpCAM), thereby recruiting T-cell activation
      to the tumor cell surface. A further sophistication involves the engineering of
      trifunctional derivatives such as the clinically approved agent, catumaxomab.
      Catumaxomab has antigen-binding arms that engage CD3 and EpCAM and a constant
      domain that recruits Fc receptor-bearing cells, notably monocytes, dendritic
      cells, and natural killer cells. Owing to this triangular binding capability,
      catumaxomab can activate both innate and adaptive immune effector mechanisms in
      addition to promoting immunologic memory. Recent data indicate that this agent
      can also promote immunogenic cell death, particularly when used in combination
      with selected chemotherapeutic agents such as oxaliplatin.

PMID- 24014597
TI  - TIG1 promotes the development and progression of inflammatory breast cancer
      through activation of Axl kinase.
AB  - Inflammatory breast cancer (IBC) is the most lethal form of breast cancer, but
      the basis for its aggressive properties are not fully understood. In this study,
      we report that high tumoral expression of TIG1 (RARRES1), a functionally
      undefined membrane protein, confers shorter survival in patients with IBC. TIG1
      depletion decreased IBC cell proliferation, migration, and invasion in vitro and
      inhibited tumor growth of IBC cells in vivo. We identified the receptor tyrosine
      kinase, Axl, as a TIG1-binding protein. TIG1 interaction stablilized Axl by
      inhibiting its proteasome-dependent degradation. TIG1-depleted IBC cells
      exhibited reduced Axl expression, inactivation of NF-kappaB, and downregulation
      of matrix metalloproteinase-9, indicating that TIG1 regulates invasion of IBC
      cells by supporting the Axl signaling pathway in IBC cells. Consistent with these
      results, treatment of IBC cells with the Axl inhibitor SGI-7079 decreased their
      malignant properties in vitro. Finally, TIG1 expression correlated positively
      with Axl expression in primary human IBC specimens. Our findings establish that
      TIG1 positively modifies the malignant properties of IBC by supporting Axl
      function, advancing understanding of its development and rationalizing TIG1 and
      Axl as promising therapeutic targets in IBC treatment.

PMID- 24014598
TI  - Oral contraceptive use and risk of breast, cervical, colorectal, and endometrial
      cancers: a systematic review.
AB  - Oral contraceptives may influence the risk of certain cancers. As part of the
      AHRQ Evidence Report, Oral Contraceptive Use for the Primary Prevention of
      Ovarian Cancer, we conducted a systematic review to estimate associations between
      oral contraceptive use and breast, cervical, colorectal, and endometrial cancer
      incidence. We searched PubMed, Embase, and Cochrane Database of Systematic
      Reviews. Study inclusion criteria were women taking oral contraceptives for
      contraception or ovarian cancer prevention; includes comparison group with no
      oral contraceptive use; study reports quantitative associations between oral
      contraceptive exposure and relevant cancers; controlled study or pooled patient
      level meta-analyses; sample size for nonrandomized studies >=100; peer-reviewed,
      English-language; published from January 1, 2000 forward. Random-effects meta
      analyses were conducted by estimating pooled ORs with 95% confidence intervals
      (CIs). We included 44 breast, 12 cervical, 11 colorectal, and 9 endometrial
      cancers studies. Breast cancer incidence was slightly but significantly increased
      in users (OR, 1.08; CI, 1.00-1.17); results show a higher risk associated with
      more recent use of oral contraceptives. Risk of cervical cancer was increased
      with duration of oral contraceptive use in women with human papillomavirus
      infection; heterogeneity prevented meta-analysis. Colorectal cancer (OR, 0.86;
      CI, 0.79-0.95) and endometrial cancer incidences (OR, 0.57; CI, 0.43-0.77) were
      significantly reduced by oral contraceptive use. Compared with never use, ever
      use of oral contraceptives is significantly associated with decreases in
      colorectal and endometrial cancers and increases in breast cancers. Although
      elevated breast cancer risk was small, relatively high incidence of breast
      cancers means that oral contraceptives may contribute to a substantial number of
      cases.

PMID- 24014599
TI  - Influence of cell loss after vitrification or slow-freezing on further in vitro
      development and implantation of human Day 3 embryos.
AB  - STUDY QUESTION: Is the effect of cell loss on further cleavage and implantation
      different for vitrified than for slowly frozen Day 3 embryos? SUMMARY ANSWER:
      Vitrified embryos develop better overnight than slowly frozen embryos, regardless
      of the number of cells lost, but have similar implantation potential if further
      cleavage occurs overnight. WHAT IS KNOWN ALREADY: After slow-freezing, similar
      implantation rates have been obtained for intact 4-cell embryos or 4-cell embryos
      with 1 cell damaged. For slowly frozen Day 3 embryos, lower implantation rates
      have been observed when at least 25% of cells were lost. Other studies reported
      similar implantation potential for 7- to 8-cell embryos with 0, 1 or 2 cells
      damaged. No data are available on further development of vitrified embryos in
      relation to cell damage. STUDY DESIGN, SIZE, DURATION: Survival and overnight
      cleavage were retrospectively assessed for 7664 slowly frozen Day 3 embryos
      (study period: January 2004-December 2008) and 1827 vitrified embryos (study
      period: April 2010-September 2011). Overnight cleavage was assessed according to
      cell stage at cryopreservation and post-thaw cell loss for both protocols. The
      relationship between cell loss and implantation rate was analysed in a subgroup
      of single-embryo transfers (SETs) with 780 slowly frozen and 294 vitrified
      embryos. PARTICIPANTS/MATERIALS, SETTING, METHODS: Embryos with >=6 blastomeres
      and <=20% fragmentation were cryopreserved using slow controlled freezing [with
      dimethyl sulphoxide (DMSO) as cryoprotectant] or closed vitrification [with DMSO
      ethylene glycol (EG)-sucrose (S) as cryoprotectants]. Only embryos with >=50% of
      cells intact after thawing were cultured overnight and were only transferred if
      further cleaved. For each outcome, logistic regression analysis was performed.
      MAIN RESULTS AND ROLE OF CHANCE: Survival was 94 and 64% after vitrification and
      slow-freezing respectively. Logistic regression analysis showed that overnight
      cleavage of surviving embryos was higher after vitrification than after slow
      freezing (P < 0.001) and decreased according to the degree of cell damage (P <
      0.001). If the embryo continued to cleave after thawing, there was no effect of
      the number of cells lost or the cryopreservation method on its implantation
      potential. The implantation rates of embryos with 0, 1 or 2 cells damaged were,
      respectively, 21% (n = 114), 21% (n = 28) and 20% (n = 12) after slow-freezing
      and 20% (n = 50), 21% (n = 5) and 27% (n = 4) after vitrification. LIMITATIONS,
      REASONS FOR CAUTION: This analysis is retrospective and study periods for
      vitrification and slow-freezing are different. The number of SETs with vitrified
      embryos is limited. However, a large number of vitrified embryos were available
      to analyse the further cleavage of surviving embryos. WIDER IMPLICATIONS OF THE
      FINDINGS: Although it is not proved that vitrified embryos are more viable than
      slowly frozen embryos in terms of pregnancy outcome, vitrification yields higher
      survival rates, better overnight development and higher transfer rates per embryo
      warmed. This increases the number of frozen transfer cycles originating from a
      single treatment and might result in a better cumulative clinical outcome. Based
      on the present data, the policy to warm an extra embryo before overnight culture
      depends on the cell stage at cryopreservation and the cell damage after warming.
      For 8-cell embryos, up to two cells may be damaged compared with only one cell
      for 6- to 7-cell embryos, before an additional embryo is warmed. STUDY
      FUNDING/COMPETING INTEREST(S): none.

PMID- 24014600
TI  - Identification of CD147 (basigin) as a mediator of trophoblast functions.
AB  - STUDY QUESTION: Does CD147 regulate trophoblast functions in vitro? SUMMARY
      ANSWER: CD147 exists as a receptor complex on human trophoblast and regulates the
      implantation, invasion and differentiation of trophoblast. WHAT IS KNOWN ALREADY:
      CD147 is a membrane protein implicated in a variety of physiological and
      pathological conditions due to its regulation of cell-cell recognition, cell
      differentiation and tissue remodeling. Reduced placental CD147 expression is
      associated with pre-eclampsia, but the mechanism of actions remains unclear.
      STUDY DESIGN, SIZE, DURATION: A loss of function approach or functional blocking
      antibody was used to study the function of CD147 in primary human
      cytotrophoblasts isolated from first trimester termination of pregnancy and/or in
      the BeWo cell line, which possesses characteristics of human cytotrophoblasts.
      PARTICIPANTS/MATERIALS, SETTING METHODS: CD147 expression was analyzed by
      immunofluorescence staining and western blotting. CD147-associated protein
      complex on plasma membrane were separated by blue native gel electrophoresis and
      identified by reversed-phase liquid chromatography coupled with quadrupole time
      of-flight hybrid mass spectrometer. Cell proliferation and invasion were
      determined by fluorometric cell proliferation assays and transwell invasion
      assays, respectively. Matrix metalloproteinases (MMPs) and urokinase plasminogen
      activator (uPA) activities were measured by gelatin gel zymography and uPA assay
      kits, respectively. Cell migration was determined by wound-healing assays. Cell
      fusion was analyzed by immunocytochemistry staining of E-cadherin and 4',6
      diamidino-2-phenylindole. The transcripts of matrix proteinases and trophoblast
      lineage markers were measured by quantitative PCR. Extracellular signal-regulated
      kinase (ERK) activation was analyzed by western blot using antibodies against
      ERKs. MAIN RESULTS AND THE ROLE OF CHANCE: CD147 exists as protein complexes on
      the plasma membrane of primary human cytotrophoblasts and BeWo cells. Several
      known CD147-interacting partners, including integrin beta1 and monocarboxylate
      transporter-1, were identified. Suppression of CD147 by siRNA significantly (P <
      0.05) reduced trophoblast-endometrial cell interaction, cell invasion,
      syncytialization, differentiation and ERK activation of BeWo cells. Consistently,
      anti-CD147 functional blocking antibody suppressed the invasiveness of primary
      human cytotrophoblasts. The reduced invasiveness was probably due to the
      restrained (P < 0.05) enzyme activities of MMP-2, MMP-9 and uPA. LIMITATIONS,
      REASONS FOR CAUTION: Most of the above findings are based on BeWo cell lines.
      These results need to be confirmed with human first trimester primary
      cytotrophoblast. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study on
      the role of CD147 in trophoblast function. Further investigation on the function
      of CD147 and its associated protein complexes will enhance our understanding on
      human placentation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported
      in part by the University of Hong Kong Grant 201011159200. The authors have no
      competing interests to declare.

PMID- 24014602
TI  - Reply: consensus on current management of endometriosis.

PMID- 24014601
TI  - Circulating insulin-like factor 3 (INSL3) in healthy and infertile women.
AB  - STUDY QUESTION: How does insulin-like factor 3 (INSL3) concentration in blood
      vary across the menstrual cycle in women? SUMMARY ANSWER: INSL3 is secreted by
      the theca interna cells of growing antral follicles and is phasic in its
      expression. WHAT IS KNOWN ALREADY: The relaxin-like hormone INSL3 is known to be
      expressed in follicles of several mammal species, and was recently shown in cows
      to be specifically secreted into the bloodstream by growing antral follicles,
      corresponding to follicular waves. In males INSL3 is known to be acutely
      independent of the hormones of the hypothalamic-pituitary-gonadal axis,
      suggesting that in women INSL3 might be a novel biomarker for antral follicle
      recruitment and development. STUDY DESIGN, SIZE, DURATION: Two cohorts of women
      were studied. First, 18 healthy women of reproductive age were followed
      longitudinally for one and a half cycles, with blood sampling and hormone
      measurement every 2-3 days. A second cohort comprised a cross-sectional study of
      909 women attending an infertility clinic, with a single blood sample taken at
      entry, together with other clinical and hormonal parameters.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples from both retrospective
      cohorts were analyzed for INSL3 using a highly sensitive time-resolved
      fluorescent immunoassay, and data were analyzed in comparison with other clinical
      and hormonal parameters. MAIN RESULT AND THE ROLE OF CHANCE: For young healthy
      women of reproductive age, we showed a phasic expression of INSL3 corresponding
      to antral follicle growth in both the follicular and luteal phases of the cycle,
      which was significantly (P < 0.05) elevated compared with that during menses. For
      women attending an infertility clinic, those with diagnosed polycystic ovarian
      syndrome indicated significantly (P < 0.0005) greater circulating INSL3 levels
      and those with low ovarian reserve showed significantly (P < 0.002) decreased
      INSL3 values. LIMITATIONS, REASONS FOR CAUTION: These were retrospective studies
      and the results were obtained from natural cycles only, with their inherent
      variability. WIDER IMPLICATIONS OF THE FINDINGS: We show for the first time that
      INSL3 in women does vary across the menstrual cycle, and appears to reflect the
      number of growing antral follicles recruited within both follicular and luteal
      phases. STUDY FUNDING/COMPETING INTEREST(S): The present retrospective study was
      largely supported by departmental funds. There were no competing interests.

PMID- 24014603
TI  - Follicular flushing and in vitro fertilization outcomes in the poorest
      responders: a randomized controlled trial.
AB  - STUDY QUESTION: Does follicular flushing during oocyte retrieval improve the
      number of oocytes retrieved in the poorest responders? SUMMARY ANSWER: Follicular
      flushing in the poorest responders does not increase the number of oocytes
      retrieved and may result in lower implantation and clinical pregnancy rates. WHAT
      IS KNOWN ALREADY: Although previous studies have shown no beneficial effect of
      follicular flushing in normal responders, no study has demonstrated a detrimental
      effect and many IVF centers continue to perform this technique in poor
      responders. Data on follicular flushing in this patient group are limited, with
      no randomized trial to date assessing its utility in the poorest responders.
      STUDY DESIGN, SIZE, DURATION: This randomized controlled trial compared the
      effects of follicular flushing and direct aspiration on IVF outcomes in the
      poorest responders, defined as having four or fewer follicles >=12 mm on the day
      of hCG administration. Fifty patients were randomized during the 12-month
      enrollment period. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients were
      treated at an academic fertility center at Weill Cornell Medical College, New
      York. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty women were randomized to
      follicular flushing (n = 25) or direct aspiration (n = 25). One patient in the
      direct aspiration group was canceled prior to oocyte retrieval for premature
      ovulation and was included in the intent-to-treat analysis. There was no
      difference in the number of oocytes retrieved with a median (IQR) of 4 (2-6) in
      the aspiration group versus 3 (2-5) in the flushing group (95% CI: -0.78, 1.98; P
      = 0.41). Patients who underwent follicular flushing had significantly fewer
      embryos transferred {1.7 [standard deviation (SD) 0.6] versus 2.5 (SD 1.2), P =
      0.03}, a lower implantation rate (5.3 versus 34.2%, P = 0.006) and a lower
      clinical pregnancy rate (4 versus 36%, P = 0.01). The difference in pregnancy
      rates remained significant after adjusting for embryos transferred. LIMITATIONS,
      REASONS FOR CAUTION: Findings, including results for secondary outcome measures,
      may not be generalizable to natural IVF cycles as these were excluded from the
      study. WIDER IMPLICATIONS OF THE FINDINGS: This is the first randomized trial to
      evaluate the utility of follicular flushing in the poorest responders, and the
      first to demonstrate a potentially detrimental effect of flushing on IVF
      outcomes. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER:
      NCT 01558141.

PMID- 24014604
TI  - Uterine length and fertility outcomes: a cohort study in the IVF population.
AB  - STUDY QUESTION: What is the relationship between pre-cycle uterine length and IVF
      outcome (chemical pregnancy, clinical pregnancy, spontaneous abortion and live
      birth)? SUMMARY ANSWER: Women at extremes of uterine length (<7.0 or >9.0 cm)
      were less likely to achieve live birth and women with uterine lengths <6.0 cm
      were also more likely to experience spontaneous abortion. WHAT IS KNOWN ALREADY:
      A prospective study of 807 women published in 2000 found that implantation and
      clinical pregnancy rates were highest in women with uterine lengths between 7.0
      and 9.0 cm, though the difference was not significant. The relationship between
      pre-cycle uterine length and live birth has not been evaluated. STUDY DESIGN,
      SIZE, DURATION: A retrospective cohort study of all cycles performed after
      uterine length measurement at an academic hospital IVF clinic from 2001 to 2012.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 8981 fresh cycles were
      performed in 5120 adult women with normal uterine anatomy. Women with uterine
      anomalies (unicornuate, bicornuate, septate or uterus exposed to
      diethylstilbestrol) were excluded and women with fibroids were identified for
      subanalysis. Uterine length was measured by uterine sounding. Cycles were divided
      by uterine length into groups: <6.0 cm (very short, n = 76), 6.0-6.9 cm (short, n
      = 2014), 7.0-7.9 cm (referent, n = 4984), 8.0-8.9 cm (long, n = 1664) and >=9 cm
      (very long, n = 243). Multivariate logistic regression (first-cycle analyses) and
      generalized estimating equations (all-cycle analyses) were adjusted for age,
      fibroids and ART treatment (assisted hatching, intracytoplasmic sperm injection)
      to generate relative risk (RR) of cycle outcomes by uterine length. MAIN RESULTS
      AND THE ROLE OF CHANCE: Median uterine length in the IVF population was 7.0 cm
      (interquartile range 7.0-7.8) and was positively associated with BMI (P < 0.001)
      and fibroids (P = 0.02). Compared with the referent group, women with uterine
      lengths <6.0 cm were half as likely to achieve live birth (RR: 0.53; 95%
      confidence interval (CI): 0.35-0.81) and women with lengths of 6.0-6.9 cm were
      also less likely (RR: 0.91; CI: 0.85-0.98). Cubic regression spline identified a
      significant inverse U-shaped association whereby women with uterine lengths <7.0
      or >9.0 cm were less likely to achieve live birth. Women with lengths <6.0 cm
      were also more likely to experience spontaneous abortion (RR: 2.16; CI: 1.23
      3.78). Results remained consistent when excluding women with a uterine factor
      diagnosis (n = 8823), when limiting to the first cycle at our institution (n =
      5120) and when further restricting to first-ever cycles (n = 3941). LIMITATIONS,
      REASONS FOR CAUTION: Optimal assessment of uterine length by ultrasound was not
      feasible due to time and cost limitations, though uterine sounding is a
      clinically relevant measurement allowing for results with practical implications.
      Findings from our predominantly Caucasian clinic population may not be
      generalizable to infertile populations with different ethnic compositions. WIDER
      IMPLICATIONS OF THE FINDINGS: Reproducibility of results would solidify findings
      and inform patient counseling in women undergoing IVF. STUDY FUNDING/COMPETING
      INTEREST(S): No funding was sought for this investigation. MD declares
      relationships with UpToDate (royalties) and WINFertlity (consultant).

PMID- 24014605
TI  - Increased protein expression of LHCG receptor and 17alpha-hydroxylase/17-20-lyase
      in human polycystic ovaries.
AB  - STUDY QUESTION: Does the expression of LHCG receptor (LHCGR) protein and key
      enzymes in the androgen biosynthetic pathway differ in normal human versus
      polycystic ovarian tissue? SUMMARY ANSWER: LHCGR and 17alpha-hydroxylase/17-20
      lyase (CYP17A1) protein levels are increased in polycystic ovaries (PCOs). WHAT
      IS KNOWN ALREADY: The predominant source of excess androgen secretion in women
      with polycystic ovary syndrome (PCOS) is ovarian theca cells but few studies have
      directly assessed the presence and abundance of protein for key molecules
      involved in androgen production by theca, including LHCGR and the rate-limiting
      enzyme in androgen production, CYP17A1. STUDY DESIGN, SIZE, DURATION: This is a
      laboratory-based, cross-sectional study comparing protein expression of key
      molecules in the androgen biosynthetic pathway in archived ovarian tissue from
      women with normal ovaries (n = 10) with those with PCOs (n = 16).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: A quantitative morphometric study was
      performed using sections of archived human ovaries (n = 26) previously
      characterized as normal or polycystic. The distribution and abundance of LHCGR,
      CYP17A1, 3beta-hydroxysteroid dehydrogenase type 2 (3betaHSDII) and 17beta
      hydroxysteroid dehydrogenase type 5 (17betaHSD5) proteins were evaluated by
      immunohistochemistry and quantified. MAIN RESULTS AND THE ROLE OF CHANCE: A
      higher proportion of theca cells from anovulatory PCO expressed LHCGR protein
      when compared with control ovaries (P = 0.01). A significant increase in the
      intensity of immunostaining for CYP17A1 was identified in antral follicles in
      sections of PCO compared with ovaries from normal women (P = 0.04). LIMITATIONS,
      REASONS FOR CAUTION: As the study used formalin-fixed ovarian tissue sections, it
      was not possible to carry out studies 'in vitro' using the same ovarian tissues
      in order to also demonstrate increased functional activity of LHCGR and CYP17A1.
      WIDER IMPLICATIONS OF THE FINDINGS: The data are in keeping with the results of
      previous studies in isolated theca cells and support the notion of an intrinsic
      abnormality of theca cell androgen production in women with PCOS. STUDY
      FUNDING/COMPETING INTEREST(S): The research was supported by a Programme Grant,
      G0802782, from the Medical Research Council (MRC) UK and by the National
      Institute for Health Research (NIHR) Biomedical Research Centre based at Imperial
      College Healthcare NHS Trust and Imperial College London. F.V.C was supported by
      Capes Foundation (Brazilian Ministry of Education). The authors have no conflicts
      of interest to disclose.

PMID- 24014606
TI  - Consensus on current management of endometriosis.

PMID- 24014607
TI  - Increased risk for ovarian cancer and borderline ovarian tumours in subfertile
      women with endometriosis.
AB  - STUDY QUESTION: Is ovarian or extra-ovarian endometriosis associated with an
      increased risk of ovarian cancer and borderline ovarian tumours (BOT)? SUMMARY
      ANSWER: We found a 3- to 8-fold increased risk of ovarian tumours associated with
      endometriosis: the magnitude of the risk increase depended on the definition of
      endometriosis. WHAT IS KNOWN ALREADY: There is increasing evidence of an
      association between endometriosis and increased risk of ovarian cancer. However,
      most reports were based on self-reported diagnosis of endometriosis. STUDY
      DESIGN, SIZE, DURATION: We conducted a nationwide historic cohort study among
      women with subfertility problems between 1980 and 1995. For this analysis we
      selected all cohort members with endometriosis, and a comparison group of
      subfertile women (male factor or idiopathic) without endometriosis (total cohort
      of 8904 women). Median follow-up time was 15.2 for the entire study population.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: For this analysis we selected all
      cohort members with (n = 3657) and without (n = 5247) evidence of endometriosis.
      Seventy-eight per cent of diagnoses of endometriosis were confirmed by pathology
      report, and 22% was self-reported endometriosis (positive predictive value of
      73%). We linked the cohort with the Dutch Pathology Database and the Netherlands
      Cancer Registry to assess the occurrence of ovarian cancer and BOT between
      January 1989 and June 2007. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a
      substantially increased risk of all ovarian malignancies combined in women with
      endometriosis when we based the definition of endometriosis on self-report,
      medical records information at subfertility treatment and/or the nationwide
      pathology database (hazard ratio (HR) 8.2; 95% confidence interval (CI) 3.1
      21.6). The HR associated with endometriosis was 12.4 (95% CI 2.8-54.2) for
      ovarian cancer and 5.5 (95% CI 1.5-20.2) for BOT. When we excluded information
      from the pathology database, HRs were 3.0 (95% CI 1.5-6.1) for all ovarian
      tumours, 4.3 (95% CI 1.6-11.2) for ovarian cancer and 1.9 (95% CI 0.6-5.8) for
      BOT. Both ovarian and extra-ovarian endometriosis carried a significantly
      increased risk for ovarian cancer and BOT. LIMITATIONS, REASONS FOR CAUTION: We
      did not have information on oral contraceptive use and parity for 23.4 and 3.4%,
      of women in the analytic cohort, respectively. Furthermore, a limitation of our
      study, and also of other studies, is that the date of diagnosis of endometriosis
      is usually made long after the onset of the disease. Also, the number of cases in
      the cohort is small (n = 34), resulting in wide CIs. WIDER IMPLICATIONS OF THE
      FINDINGS: The fact that endometriosis was assessed before diagnosis of ovarian
      malignancy and the high degree of medical confirmation in our study likely
      contribute to the validity of our estimate of a 3- to 8-fold increased risk of
      ovarian tumours associated with endometriosis. The risk of ovarian malignancies
      associated with endometriosis was much higher in analyses including information
      on endometriosis from the nationwide pathology database, implying that risk
      estimates from studies using self-reported information on endometriosis may be
      too low due to non-differential misclassification bias. STUDY FUNDING/COMPETING
      INTEREST(S): None. TRIAL REGISTRATION NUMBER: None.

PMID- 24014608
TI  - First reported clinical pregnancy following heterotopic grafting of cryopreserved
      ovarian tissue in a woman after a bilateral oophorectomy.
AB  - Ovarian tissue cryopreservation and transplantation is a form of fertility
      preservation offered to young women at high risk of losing ovarian function after
      cancer treatment. While there have been successful births resulting from
      orthotopic site grafts, we report the first case of an ongoing pregnancy from a
      heterotopic graft in a patient who had previously undergone bilateral
      oopherectomy for a granulosa cell tumour. Frozen-thawed ovarian tissue was
      transplanted to the anterior abdominal wall. Subsequent ovarian stimulation and
      transabdominal ultrasound-guided oocyte retrieval from the grafts resulted in two
      oocytes. These were fertilized with ICSI and two embryos were transferred. Serial
      ultrasounds have confirmed an ongoing 26-week intrauterine twin pregnancy. Thus,
      this first demonstration of a pregnancy from a heterotopic graft site provides
      unequivocal evidence that cryopreservation preserves complete follicle
      development and that normal ovarian function can occur at a non-ovarian site.
      This provides optimism for further efforts to assist women who have had
      oophorectomy and pelvic surgery or radiotherapy, without an appropriate
      orthotopic site for grafting. 

PMID- 24014609
TI  - Epistasis between IGF2R and ADAMTS19 polymorphisms associates with premature
      ovarian failure.
AB  - STUDY QUESTION: Do single nucleotide polymorphisms (SNPs) or synergistic
      interactions between SNPs and diplotypes within the insulin-like growth factor 2
      receptor (IGF2R) and ADAM metallopeptidase with thrombospondin type 1 motif, 19
      (ADAMTS19), contribute to premature ovarian failure (POF)? SUMMARY ANSWER:
      Synergistic interactions were detected between SNPs, including a non-synonymous
      SNP, and diplotypes within IGF2R and ADAMTS19 which may contribute to POF;
      however, there was no correlation with POF in a single SNP model after Bonferroni
      correction. WHAT IS KNOWN ALREADY: IGF2R regulates free IGF2 level, which is
      involved in steroidogenesis in bovine granulosa cells. ADAMTS19 expression is
      higher in the murine embryonic ovary than in the embryonic testis during sexual
      differentiation, and an ADAMTS19 SNP (rs246246) showed a possible association
      with POF in a genome-wide association study in Caucasian women. STUDY DESIGN,
      SIZE, DURATION: This study analyzed interactions between SNPs and diplotypes
      within IGF2R and ADAMTS19 as well as SNPs within the two genes. In Stage I, a
      total of 120 patients with POF and 152 female controls were recruited. All
      patients were diagnosed with POF at the CHA hospital in Seoul, Korea, and were
      recruited between 1994 and 2004. The 152 controls were recruited from Chungju,
      Korea, as part of another study that was conducted from April 2002 to March 2004.
      For Stage II, we obtained genotype data for an additional 1641 female controls,
      recruited in Ansung and Ansan from 2001 to 2008, from the Korean Genome
      Epidemiology Study (KoGES). PARTICIPANTS/MATERIALS, SETTING, METHODS: In Stage I,
      the GoldenGate assay with VeraCode technology was used to genotype SNPs in IGF2R
      and ADAMTS19. In Stage II, we obtained genotype data for IGF2R and ADAMTS19 using
      Affymetrix Genome-Wide Human SNP array 5.0 and imputed data by the IMPUTE program
      from the KoGES. To identify POF-associated SNPs, logistic regression analysis in
      an additive model was performed using the PLINK tool. Synergistic interactions
      between SNPs and diplotypes within IGF2R and ADAMTS19 were analyzed by logistic
      regression analysis in three alternative models. MAIN RESULTS AND THE ROLE OF
      CHANCE: In Stage I, 13 combinations of SNPs showed significant synergistic
      interactions after Bonferroni correction [the strongest association had odds
      ratio (OR) = 5.77, 95% confidence interval (CI): 2.26-14.75, P = 0.00025]. In
      Stage II and combined analyses, two and four combinations, respectively, of the
      significant results in Stage I showed significant synergistic interactions after
      Bonferroni correction. For interactions between diplotypes in block 2 of IGF2R
      and block 3 of ADAMTS19 in Stage I, we found 17 synergistic interactions with P <
      0.0001, but there was no significant interaction after Bonferroni correction. In
      Stage II and combined analyses, we found that three and seven combinations in the
      same blocks, respectively, showed significant synergistic interactions after
      Bonferroni correction (strongest association: OR = 4.12, 95% CI: 2.22-7.62, P =
      6.74E-06). LIMITATIONS, REASONS FOR CAUTION: The sample size for patients with
      POF in this study was small but, compared with recent reports describing
      associations between SNPs and POF and considering the low prevalence of POF (1%),
      the sample size is considered to be reasonable. These results should be confirmed
      in large-scale studies involving different ethnic groups. WIDER IMPLICATIONS OF
      THE FINDINGS: Our results may ultimately provide predictive markers for women at
      a high risk of POF. STUDY FUNDING/COMPETING INTERESTS: This study was supported
      by grants from Basic Science Research Program through the National Research
      Foundation of Korea (NRF), which is funded by the Ministry of Education (2009
      0093821, 2011-0010637). There are no competing interests.

PMID- 24014610
TI  - Environmental pathobiology and global opportunities.

PMID- 24014611
TI  - Pathology in context.

PMID- 24014612
TI  - Toxoplasma gondii: clues from stranded dolphins.

PMID- 24014613
TI  - Recommendations to improve collaboration and expedite acceptance of animal
      models.

PMID- 24014614
TI  - Mechanism of MTA1 protein overexpression-linked invasion. MTA1 regulation of
      hyaluronan-mediated motility receptor (HMMR) expression and function.

PMID- 24014616
TI  - Decisional involvement: actual and preferred involvement in decision-making among
      registered nurses.
AB  - Enhancing nurse involvement in decision-making is a starting point in addressing
      the nursing shortage, recruitment, and retention. The purpose of this descriptive
      comparative secondary data analysis was to describe the level of registered
      nurses' actual and preferred decisional involvement (DI) in two studies carried
      out during 2004 and 2010 and to describe the difference in the levels of actual
      and preferred DI between the 2004 study (N = 290) and the 2010 (N = 111) study in
      a Midwestern medical center after a new shared governance structure was
      implemented. In the 2004 and 2010 studies, there were statistically significant
      differences between actual and preferred levels of DI. A statistically
      significant decrease in means occurred in actual and preferred DI in 2010 as
      compared with that in 2004. A concerted effort must be made by nursing leaders to
      enhance DI, offer adequate resources, promote learning and growth, and recognize
      nursing contributions within a shared governance. 

PMID- 24014617
TI  - The efficacy of 320-detector row computed tomography for the assessment of
      preoperative pulmonary vasculature of candidates for pulmonary segmentectomy.
AB  - OBJECTIVES: The purpose of this study was to compare the efficacy of 320-detector
      row computed tomography (CT) with that of 64-detector row CT for three
      dimensional assessment of pulmonary vasculature of candidates for pulmonary
      segmentectomy. METHODS: We included 32 patients who underwent both 320- and 64
      detector CT before pulmonary segmentectomy, which was performed by cutting the
      pulmonary artery and bronchi of the affected segment followed by dissection of
      the intersegmental plane along the intersegmental vein. Before the operation,
      three-dimensional pulmonary vasculature images were obtained for each patient,
      and the arteries and intersegmental veins of the affected segments were
      identified. Two thoracic surgeons independently assessed the vessels with visual
      scoring systems, and kappa analysis was used to determine interobserver
      agreement. The Wilcoxon signed-rank test was used to compare the visual scores
      for the assessment of the visualization capabilities of the two methods. In
      addition, the final determination of pulmonary vasculature at a given site was
      made by consensus from thoracic surgeons during operation, and receiver operating
      characteristic analysis was performed to compare their efficacy of pulmonary
      vasculature assessment. Sensitivity, specificity and accuracy of either method
      were also compared by means of McNemar's test. RESULTS: Of the 32 cases, there
      were no operative complications, but 1 patient died of postoperative idiopathic
      interstitial pneumonia. Visualization scores for the pulmonary vessels were
      significantly higher for 320- than those for 64-detector CT (P < 0.0001 for the
      affected arteries and P < 0.0001 for the intersegmental veins). As for pulmonary
      vasculature assessment, the areas under the curve showed no statistically
      significant differences in between the two methods, while the specificity and
      accuracy of intersegemental vein assessment were significantly better for 320-
      than those for 64-detector row CT (P < 0.05). Interobserver agreement for the
      assessment yielded by either method was almost perfect for all cases.
      CONCLUSIONS: Three hundred and twenty-detector row CT is more useful than
      conventional 64-detector row CT for preoperative three-dimensional assessment of
      pulmonary vasculature, especially when we identify the intersegmental veins, in
      candidates for pulmonary segmentectomy.

PMID- 24014618
TI  - Successful reversal of immediate paraplegia associated with repair of acute Type
      A aortic dissection using cerebrospinal fluid drainage.
AB  - We present a case of a 49-year old man who suffered from immediate paraplegia
      upon awakening from anaesthesia after surgery for acute aortic dissection Type A.
      A catheter was promptly inserted into the spinal canal for cerebrospinal fluid
      drainage, and the cerebrospinal fluid pressure was maintained <10 cmH2O. Although
      magnetic resonance imaging showed extensive spinal cord ischaemia, the patient
      gradually recovered from the paraplegia and was able to walk by himself after
      rehabilitation. In some cases, cerebrospinal fluid drainage can be effective for
      the treatment of immediate postoperative spinal cord damage. 

PMID- 24014619
TI  - Oxidative stress and nitric oxide pathway in adult patients who are candidates
      for cardiac surgery: patterns and differences.
AB  - OBJECTIVES: We investigated whether oxidative stress and the arginine/nitric
      oxide pathway differ in control subjects and in adult patients who are candidates
      for the three most common cardiac surgical operations: coronary bypass surgery,
      aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral
      valve repair for degenerative mitral insufficiency. METHODS: In this prospective
      observational study, we studied 165 consecutive patients undergoing surgery from
      January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement
      for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for
      degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with
      cardiovascular risk factors similar to surgery patients were also studied
      (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and
      urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors
      involved in nitric oxide synthesis (arginine, symmetric and asymmetric
      dimethylarginine) were measured before surgery. Analysis of variance general
      linear models and principal component analysis were used for statistical
      analysis. RESULTS: Surgical patients had increased levels of oxidative stress and
      decreased levels of antioxidants. Increased levels of nitric oxide inhibitor
      asymmetric dimethylarginine were detected in surgical candidates, suggesting
      arginine/nitric oxide pathway impairment. Concerning the differences among
      surgical procedures, higher oxidative stress and a major imbalance of the ratio
      between substrate and inhibitors of nitric oxide synthesis were evidenced in
      patients who were candidates for mitral valve repair with respect to coronary
      bypass surgery patients and patients with calcific non-rheumatic aortic stenosis.
      CONCLUSIONS: Patients undergoing cardiac surgery have increased oxidative stress
      and a trend towards an impaired arginine/nitric oxide pathway with respect to
      Controls. Patients affected by mitral valve regurgitation show more pronounced
      perturbations in these pathways. The clinical implications of these findings need
      to be investigated.

PMID- 24014620
TI  - Is there evidence that fresh frozen plasma is superior to antithrombin
      administration to treat heparin resistance in cardiac surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was, 'in [patients with heparin resistance] is
      [treatment with FFP] superior [to antithrombin administration] in [achieving
      adequate anticoagulation to facilitate safe cardiopulmonary bypass]?' More than
      29 papers were found using the reported search, of which six 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. Antithrombin (AT) binds to heparin and increases
      the rate at which it binds to thrombin. The levels of antithrombin in the blood
      are an important aspect of the heparin dose-response curve. When the activated
      clotting time (ACT) fails to reach a target >480, this is commonly defined as
      heparin resistance (HR). Heparin resistance is usually treated with a combination
      of supplementary heparin, fresh frozen plasma (FFP) or antithrombin III
      concentrate. There is a paucity of evidence on the treatment of heparin
      resistance with FFP, with only five studies identified, including one
      retrospective study, one in vitro trial and three case reports. AT has been
      studied more extensively with multiple studies, including a crossover trial
      comparing AT to supplemental heparin and a multicentre, randomized, double blind,
      placebo-controlled trial. Antithrombin (AT) concentrate is a safe and efficient
      treatment for heparin resistance to elevate the activated clotting time (ACT). It
      avoids the risk of transfusion-related acute lung injury (TRALI), volume
      overload, intraoperative time delay and viral or vCJD transmission. Antithrombin
      concentrates are more expensive than fresh frozen plasma and may put patients at
      risk of heparin rebound in the early postoperative period. Patients treated with
      AT have a lower risk of further FFP transfusions during their stay in hospital.
      We conclude that the treatment of HR with FFP may not restore the ACT to
      therapeutic levels with adequate heparinization, but AT is efficient with
      benefits including lower volume administration, less risk of TRALI and lower risk
      of transfusion-related infections. 

PMID- 24014621
TI  - Successful treatment of tumor-induced osteomalacia due to an intracranial tumor
      by fractionated stereotactic radiotherapy.
AB  - CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome,
      characterized by tumor secretion of fibroblast growth factor-23 (FGF23) causing
      hypophosphatemia due to renal phosphate wasting. TIO is usually caused by small,
      benign, difficult-to-localize, mesenchymal tumors. Although surgery with wide
      excision of tumor borders is considered the "gold standard" for definitive
      therapy, it can be associated with considerable morbidity depending on the
      location. To date, radiation therapy has not been considered as an effective
      treatment modality in TIO. OBJECTIVE: A 67-year-old female presented with
      multiple nontraumatic fractures, progressive bone pain, and muscle weakness for 4
      years. She was found to have biochemical evidence of urinary phosphate wasting
      with low serum phosphorus, low-normal serum calcium, normal 25-hydroxyvitamin D
      and 1,25-dihydroxyvitamin D, and high serum FGF23 levels. TIO was diagnosed.
      Selective venous sampling for FGF23 confirmed that a 1.7-cm left frontal mass,
      radiographically similar to a meningioma, was the causative tumor. She declined
      surgery due to fear of complications and instead underwent fractionated
      stereotactic radiotherapy for 6 weeks. RESULTS: In less than 4 years after
      radiation therapy, she was successfully weaned off phosphorus and calcitriol,
      starting from 2 g of oral phosphorus daily and 1 MUg of calcitriol daily. Her
      symptoms have resolved, and she has not had any new fractures. CONCLUSIONS:
      Stereotactic radiotherapy was an effective treatment modality for TIO in our
      patient. Fractionated stereotactic radiation therapy represents an alternative to
      surgery for patients with TIO who are not surgical candidates or who decline
      surgery.

PMID- 24014622
TI  - Endometrial Intracrinology--generation of an estrogen-dominated microenvironment
      in the secretory phase of women.
AB  - CONTEXT: The human endometrium is a complex multicellular tissue subject to
      cyclical fluctuations in ovarian-derived steroid hormones. Fertile cycles are
      characterized by differentiation (decidualization) of endometrial stromal cells
      (ESC). OBJECTIVE: To determine the impact of human stromal cell decidualization
      on biosynthesis and secretion of estrogens. DESIGN: Primary cell culture was
      used. Cells were decidualized in vitro. Some cultures were treated with an
      aromatase inhibitor. SETTING: A University Research Institute. PATIENTS: Primary
      ESC were derived from women with normal menstrual cycles (n = 12). None of the
      women were receiving hormonal therapy or suffering from endometriosis. MAIN
      OUTCOME MEASUREMENTS: Expression of mRNA and protein encoded by the aromatase
      (CYP19A1) and 3-beta-hydroxysteroid dehydrogenase (HSD3B1) genes was assessed.
      Aromatase activity was measured using a tritiated water assay; steroid metabolism
      was determined using thin layer chromatography. Estrone (E1) and estradiol (E2)
      in cell culture media were measured by ELISA. RESULTS: Decidualization induced a
      two-fold increase in aromatase mRNA. Aromatase protein was only detected in
      decidualized ESC. 3-beta-Hydroxysteroid dehydrogenase protein was present in ESC
      both before and after decidualization; concentrations appeared unchanged. The
      existence of functional aromatase in decidualized ESC was confirmed; E1 and E2
      were secreted into culture media in decidualized ESC and concentrations were
      reduced when cells were incubated with an aromatase inhibitor. Decidualization
      resulted in reduced metabolism of E2 and an increase in the ratio of E2:E1.
      CONCLUSIONS: Decidualization is characterized by an increase in aromatase
      expression/activity favoring the generation of an E2-dominated estrogen
      microenvironment within the endometrial stroma.

PMID- 24014623
TI  - Gemmobacter megaterium sp. nov., isolated from coastal planktonic seaweeds.
AB  - A Gram-stain-negative, non-motile and aerobic bacterium, designated CF17(T), was
      isolated from coastal planktonic seaweeds, East China Sea. The isolate grew at 18
      37  degrees C (optimum 25-28  degrees C), pH 6.5-9.0 (optimum 7.0-8.0) and with 0
      5 % NaCl (optimum 1-2 %, w/v) and 0.5-10 % sea salts (optimum 2-3 %, w/v). Growth
      of strain CF17(T) could be stimulated prominently by supplementing the growth
      medium with the autoclaved supernatant of a culture of strain CF5, which was
      isolated from the same sample along with strain CF17(T). The cell morphology of
      strain CF17(T) was a bean-shaped rod consisting of a swollen end and a long
      prostheca. The phylogenetic analysis of 16S rRNA gene sequences indicated that
      strain CF17(T) clustered with Gemmobacter nectariphilus DSM 15620(T) within the
      genus Gemmobacter. The DNA G+C content of strain CF17(T) was 61.4 mol%. The
      respiratory quinone was ubiquinone Q-10. The major fatty acids included C18 :
      1omega7c and C18 : 0. The polar lipids of strain CF17(T) consisted of
      phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two
      uncharacterized phospholipids, one uncharacterized aminolipid, three
      uncharacterized glycolipids and one uncharacterized lipid. On the basis of
      phenotypic, phylogenetic and chemotaxonomic data, strain CF17(T) ( = CGMCC
      1.11024(T) = JCM 18498(T)) is considered to represent a novel species of the
      genus Gemmobacter, for which the name Gemmobacter megaterium sp. nov. is
      proposed. 

PMID- 24014625
TI  - Cloacibacterium haliotis sp. nov., isolated from the gut of an abalone, Haliotis
      discus hannai.
AB  - A novel Gram-stain-negative, aerobic, non-motile, yellow-pigmented and rod-shaped
      bacterium, designated strain WB5(T), was isolated from the intestinal tract of an
      abalone, Haliotis discus hannai, collected from the northern coast of Jeju in
      Korea. The isolate grew optimally at 30  degrees C, at pH 7 and in the presence
      of 0.5 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences
      indicated that strain WB5(T) was clustered in the genus Cloacibacterium and
      shared the highest sequence similarity with C. normanense (98.2 % similarity).
      The predominant fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH. Menaquinone-6
      was the major respiratory quinone. The genomic DNA G+C content was 29.6 mol%. The
      DNA-DNA hybridization values indicated <22 % genomic relatedness with other
      members of the genus Cloacibacterium. The results of physiological, biochemical,
      chemotaxonomic and genotypic analyses showed that strain WB5(T) represents a
      novel species of the genus Cloacibacterium, for which the name Cloacibacterium
      haliotis sp. nov. is proposed. The type strain is WB5(T) ( = KACC 17210(T) = JCM
      18869(T)). 

PMID- 24014624
TI  - Scheffersomyces parashehatae f.a., sp. nov., Scheffersomyces xylosifermentans
      f.a., sp. nov., Candida broadrunensis sp. nov. and Candida manassasensis sp.
      nov., novel yeasts associated with wood-ingesting insects, and their ecological
      and biofuel implications.
AB  - During a survey of yeasts associated with wood-ingesting insects, 69 strains in
      the Scheffersomyces clade and related taxa were isolated from passalid and
      tenebrionid beetles and the decayed wood inhabited by them. The majority of these
      yeasts was found to be capable of fermenting xylose, and was recognized as
      Scheffersomyces stipitis or its close relative Scheffersomyces illinoinensis,
      which are known to be associated with wood-decaying beetles and rotten wood.
      Yeasts in 'Scheffersomyces' ( = Candida) ergatensis and 'Scheffersomyces' ( =
      Candida) coipomoensis were also frequently isolated. The remaining six strains
      were identified as representing four novel species in the genera Scheffersomyces
      and Candida based on multilocus sequence analyses of nuclear rRNA genes and four
      protein-coding genes, as well as other taxonomic characteristics. Two xylose
      fermenting species, Scheffersomyces parashehatae f.a., sp. nov. (type strain ATCC
      MYA-4653(T) = CBS 12535(T) = EH045(T); MycoBank MB805440) and Scheffersomyces
      xylosifermentans f.a., sp. nov. (type strain ATCC MYA-4859(T) = CBS 12540(T) =
      MY10-052(T); MycoBank MB805441), formed a clade with Scheffersomyces shehatae and
      related Scheffersomyces species. Interestingly, S. xylosifermentans can survive
      at 40  degrees C, which is a rare property among xylose-fermenting yeasts.
      Candida broadrunensis sp. nov. (type strain ATCC MYA-4650(T) = CBS 11838(T) =
      EH019(T); MycoBank MB805442) is a sister taxon of C. ergatensis, while Candida
      manassasensis sp. nov. (type strain ATCC MYA-4652(T) = CBS 12534(T) = EH030(T);
      MycoBank MB805443) is closely related to Candida palmioleophila in the Candida
      glaebosa clade. The multilocus DNA sequence comparisons in this study suggest
      that the genus Scheffersomyces needs to be circumscribed to the species near S.
      stipitis (type species) and S. shehatae that can be characterized by the ability
      to ferment xylose. 

PMID- 24014628
TI  - Materials recovery--a challenge for municipal solid waste managers.

PMID- 24014626
TI  - Kodamaea transpacifica f.a., sp. nov., a yeast species isolated from ephemeral
      flowers and insects in the Galapagos Islands and Malaysia: further evidence for
      ancient human transpacific contacts.
AB  - Twenty-four yeast strains were isolated from ephemeral flowers of Ipomoea spp.
      and Datura sp. and their associated insects in the Galapagos Archipelago,
      Ecuador, and from Ipomoea spp. and associated insects in the Cameron Highlands,
      Malaysia. Sequences of the D1/D2 domains of the large subunit rRNA gene indicated
      that these strains belong to a novel yeast species of the Kodamaea clade,
      although the formation of ascospores was not observed. The closest relative is
      Candida restingae. The human-mediated dispersion of this species by transpacific
      contacts in ancient times is suggested. The name Kodamaea transpacifica f.a., sp.
      nov. is proposed to accommodate these isolates. The type strain is CLQCA-24i
      070(T) ( = CBS 12823(T) = NCYC 3852(T)); MycoBank number MB 803609. 

PMID- 24014629
TI  - We are very much amused.

PMID- 24014631
TI  - What is top of the charts? BPIFB1/LPLUNC1 localises to the bronchiolised
      epithelium in the honeycomb cysts in UIP.

PMID- 24014632
TI  - On the impermissibility of infant male circumcision: a response to Mazor (2013).
AB  - This is a response to Dr Joseph Mazor's paper 'The child's interests and the case
      for the permissibility of male infant circumcision.' I argue that Dr Mazor fails
      to prove that bodily integrity and self-determination are mere interests as
      opposed to genuine rights in the case of infant male circumcision. Moreover, I
      cast doubt on the interest calculus that Dr Mazor employs to arrive at his
      conclusions about circumcision. 

PMID- 24014633
TI  - Improving the Helsinki Declaration's guidance on research in incompetent
      subjects.
AB  - Research involving children or other incompetent subjects who are deemed unable
      to provide informed consent is complex, particularly in the case of research that
      does not directly benefit the research subjects themselves. The Helsinki
      Declaration, the World Medical Association's landmark document for research
      ethics, therefore states that incompetent research subjects must not be included
      in such research unless it entails only minimal risk and minimal burden. In this
      paper, we argue that now that research in these groups is expected to expand,
      this undifferentiated minimal risk and burden requirement does not suffice any
      more. In the upcoming revision of the Declaration, the paragraph at stake should
      be refined in such a way that it is not unnecessarily restrictive or more
      permissive than can be ethically justified. Our first recommendation is to
      stimulate research ethics committees to identify more accurately those risks and
      burdens that the research subjects must undergo solely for research purposes by
      distinguishing between two types of study procedures instead of between two types
      of studies. Our second recommendation is to allow for exceptions to the minimal
      risk and burden requirement in cases of exceptionally valuable studies that
      involve subjects who can give their assent to participate in the study and that
      involve at most a minor increase over minimal risk and/or burden. 

PMID- 24014634
TI  - Forced circumcision of men (abridged).
AB  - The forced circumcision of men is a widespread human rights abuse that often
      accompanies other human rights violations. It occurs in clashes between
      circumcising and non-circumcising cultures, or when individuals in circumcising
      cultures reject circumcision. This article documents the forced circumcision of
      men against their will, shows how evidence of forced circumcision has been
      downplayed and discounted, and outlines and discusses some measures that could
      help to reduce its prevalence. 

PMID- 24014636
TI  - The impact of smoke-free legislation on reducing exposure to secondhand smoke:
      differences across gender and socioeconomic groups.
AB  - BACKGROUND: On 11 January 2009, Taiwan expanded its smoke-free legislation to all
      indoor public places and workplaces. This study examined the impact of this
      policy on secondhand smoke (SHS) exposure in adult non-smokers, across gender and
      socioeconomic status groups (SES). METHODS: An annual sample of about 13,000
      14,000 non-smokers was drawn from cross-sectional nationwide data of Taiwan Adult
      Tobacco Behavior Surveys during 2005-2011. Logistic regressions were used to
      analyse the aggregate data to estimate the association between the 2009 smoke
      free legislation and SHS exposures in homes and workplaces. Interaction terms
      were used to examine the impact of the 2009 smoke-free policy on reducing
      differences in SHS exposure across gender, education and income groups. RESULTS:
      The 2009 policy reduced the odds of SHS exposure in homes in 2009 (OR=0.76, 95%
      CI 0.68 to 0.84) and in workplaces (year 2009: OR=0.49, 95% CI 0.39 to 0.62; year
      2010: OR=0.79, 95% CI 0.66 to 0.95). The model with interaction terms showed that
      men were more likely than women to be exposed to workplace SHS (OR=2.02, 95% CI
      1.80 to 2.27) but were less likely to be exposed to home SHS (OR=0.79, 95% CI
      0.73 to 0.86). SHS exposure in homes was significantly related to lower
      socioeconomic status, but the 2009 smoke-free policy reduced the difference in
      SHS exposure across education levels. CONCLUSIONS: The 2009 smoke-free policy
      reduced the SHS exposure for non-smokers. However, this impact on home SHS did
      not persist after 2009, and the effect of protection was unequal across gender
      and SES groups. Thus, further enforcement of smoking restrictions would be needed
      to reduce the risk of SHS exposure and improve protection against SHS risk among
      parts of the population with lower socioeconomic status.

PMID- 24014642
TI  - What's trust got to do with it? Revisiting opioid contracts.
AB  - Prescription opioid abuse (POA) is an escalating clinical and public health
      problem. Physician worries about iatrogenic addiction and whether patients are
      'drug seeking', 'abusing' and 'diverting' prescription opioids exist against a
      backdrop of professional and legal consequences of prescribing that have created
      a climate of distrust in chronic pain management. One attempt to circumvent these
      worries is the use of opioid contracts that outline conditions patients must
      agree to in order to receive opioids. Opioid contracts have received some
      scholarly attention, with trust and trustworthiness identified as key values and
      virtues. However, few articles have provided a critical account of trust and
      trustworthiness in this context, particularly when there exists disagreement
      about their role in terms of enhancing or detracting from the patient-physician
      relationship. This paper argues that opioid contracts represent a misleading
      appeal to patient-physician trust. Assuming the patient is untrustworthy may
      wrongfully undermine the credibility of the patient's testimony, which may
      exacerbate certain vulnerabilities of the person in pain. However, misplaced
      trust in certain patients may render the physician vulnerable to the potential
      harms of POA. If patients distrust their physician, or feel distrusted by them,
      this may destabilise the therapeutic relationship and compromise care. A process
      of epistemic humility may help cultivate mutual patient-physician trust.
      Epistemic humility is a collaborative effort between physicians and patients that
      recognises the role of patients' subjective knowledge in enhancing physicians'
      self-understanding of their theoretical and practice frameworks, values and
      assumptions about the motivations of certain patients who report chronic pain. 

PMID- 24014643
TI  - Tobacco smoke-related health effects induced by 1,3-butadiene and strategies for
      risk reduction.
AB  - 1,3-Butadiene (BD) is a smoke component selected by the World Health Organization
      (WHO) study group on Tobacco Product Regulation (TobReg) for mandated lowering.
      We examined the tobacco smoke-related health effects induced by BD and possible
      health impacts of risk reduction strategies. BD levels in mainstream smoke (MSS)
      from international and Canadian cigarettes and environmental tobacco smoke (ETS)
      were derived from scientific journals and international government reports. Dose
      response analyses from toxicity studies from government reports were evaluated
      and the most sensitive cancer and noncancer endpoints were selected. The risks
      were evaluated by taking the ratio (margin of exposure, MOE) from the most
      sensitive toxicity endpoint and appropriate exposure estimates for BD in MSS and
      ETS. BD is a good choice for lowering given that MSS and ETS were at levels for
      cancer (leukemia) and noncancer (ovarian atrophy) risks, and the risks can be
      significantly lowered when lowering the BD concentrations in smoke. Several risk
      reduction strategies were analyzed including a maximum level of 125% of the
      median BD value per milligram nicotine obtained from international brands as
      recommended by the WHO TobReg, tobacco substitute sheets, dual and triple carbon
      filters, and polymer-derived carbon. The use of tobacco substitute sheet with a
      polymer-derived carbon filter resulted in the most significant change in risk for
      cancer and noncancer effects. Our results demonstrate that MOE analysis might be
      a practical way to assess the impact of risk reduction strategies on human health
      in the future. 

PMID- 24014644
TI  - Early identification of clinically relevant drug interactions with the human bile
      salt export pump (BSEP/ABCB11).
AB  - A comprehensive analysis was performed to investigate how inhibition of the human
      bile salt export pump (BSEP/ABCB11) relates to clinically observed drug-induced
      liver injury (DILI). Inhibition of taurocholate (TA) transport was investigated
      in BSEP membrane vesicles for a data set of 250 compounds, and 86 BSEP inhibitors
      were identified. Structure-activity modeling identified BSEP inhibition to
      correlate strongly with compound lipophilicity, whereas positive molecular charge
      was associated with a lack of inhibition. All approved drugs in the data set (n =
      182) were categorized according to DILI warnings in drug labels issued by the
      Food and Drug Administration, and a strong correlation between BSEP inhibition
      and DILI was identified. As many as 38 of the 61 identified BSEP inhibitors were
      associated with severe DILI, including 9 drugs not previously linked to BSEP
      inhibition. Further, among the tested compounds, every second drug associated
      with severe DILI was a BSEP inhibitor. Finally, sandwich-cultured human
      hepatocytes (SCHH) were used to investigate the relationship between BSEP
      inhibition, TA transport, and clinically observed DILI in detail. BSEP inhibitors
      associated with severe DILI greatly reduced the TA canalicular efflux, whereas
      BSEP inhibitors with less severe or no DILI resulted in weak or no reduction of
      TA efflux in SCHH. This distinction illustrates the usefulness of SCHH in refined
      analysis of BSEP inhibition. In conclusion, BSEP inhibition in membrane vesicles
      was found to correlate to DILI severity, and altered disposition of TA in SCHH
      was shown to separate BSEP inhibitors associated with severe DILI from those with
      no or mild DILI.

PMID- 24014645
TI  - Endocrine disruptors differentially target ATP-binding cassette transporters in
      the blood-testis barrier and affect Leydig cell testosterone secretion in vitro.
AB  - Endocrine-disrupting chemicals (EDCs) are considered to cause testicular toxicity
      primarily via interference with steroid hormone function. Alternatively, EDCs
      could possibly exert their effects by interaction with ATP-binding cassette (ABC)
      transporters that are expressed in the blood-testis barrier. In this study, we
      investigated the effects of bisphenol A (BPA), tetrabromobisphenol A (TBBPA),
      bis(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate, perfluorooctanoic acid
      (PFOA), and perfluorooctanesulfonic acid (PFOS) on breast cancer resistance
      protein (BCRP), multidrug resistance proteins 1 and 4 (MRP1 and MRP4), and P
      glycoprotein (P-gp) using membrane vesicles overexpressing these transporters.
      BPA solely inhibited BCRP activity, whereas TBBPA, PFOA, and PFOS inhibited all
      transporters tested. No effect was observed for the phthalates. Using transporter
      overexpressing Madin-Darby canine kidney cells, we show that BPA and PFOA, but
      not TBBPA, are transported by BCRP, whereas none of the compounds were
      transported by P-gp. To investigate the toxicological implications of these
      findings, testosterone secretion and expression of steroidogenic genes were
      determined in murine Leydig (MA-10) cells upon exposure to the selected EDCs.
      Only BPA and TBBPA concentration dependently increased testosterone secretion by
      MA-10 cells to 6- and 46-fold of control levels, respectively. Inhibition of the
      Mrp's by MK-571 completely blocked testosterone secretion elicited by TBBPA,
      which could not be explained by coinciding changes in expression of steroidogenic
      genes. Therefore, we hypothesize that transporter-mediated efflux of testosterone
      precursors out of MA-10 cells is inhibited by TBBPA resulting in higher
      availability for testosterone production. Our data show the toxicological and
      clinical relevance of ABC transporters in EDC risk assessment related to
      testicular toxicity.

PMID- 24014646
TI  - Listeria monocytogenes strains encoding premature stop codons in inlA invade mice
      and guinea pig fetuses in orally dosed dams.
AB  - Listeria monocytogenes is an important food-borne bacterial pathogen and
      listeriosis can result in abortions in pregnant women. The bacterium can colonize
      food-processing environments, where specific molecular subtypes can persist for
      years. The purpose of this study was to determine the virulence potential of a
      group of food-processing persistent L. monocytogenes strains encoding a premature
      stop codon in inlA (encoding internalin A) by using two orally dosed models,
      pregnant mice and pregnant guinea pigs. A food-processing persistent strain of L.
      monocytogenes invaded placentas (n = 58; 10 % positive) and fetuses (3 %
      positive) of pregnant mice (n = 9 animals per strain), similar to a genetically
      manipulated murinized strain, EGD-e InlA(m*) (n = 61; 3 and 2 %, respectively).
      In pregnant guinea pigs (n = 9 animals per bacterial strain), a maternofetal
      strain (from a human fetal clinical fatal case) was isolated from 34 % of
      placenta samples (n = 50), whereas both food-processing persistent strains were
      found in 5 % of placenta samples (n = 36 or 37). One of the food-processing
      persistent strains, N53-1, was found in up to 8 % of guinea pig fetal liver and
      brain samples, whereas the maternofetal control was found in 6 % of fetal tissue
      samples. As the food-processing persistent strains carry a premature stop codon
      in inlA but are invasive in orally dosed pregnant mice and guinea pigs, we
      hypothesize that listerial crossing of the placental barrier can occur by a
      mechanism that is independent of an interaction between E-cadherin and InlA. 

PMID- 24014647
TI  - Articular adipose tissue resident macrophages in rheumatoid arthritis patients:
      potential contribution to local abnormalities.
AB  - OBJECTIVES: The objectives of this study were to characterize macrophages
      resident in inflamed articular adipose tissue (AAT) and non-inflamed subcutaneous
      adipose tissue (ScAT) of RA patients and to evaluate the basal and cytokine
      triggered secretory activities of these tissues. METHODS: Tissues were obtained
      from patients undergoing knee joint replacement surgery. The number of total
      CD68(+), CD14(+) and CD163(+) macrophages was evaluated by immunohistochemistry.
      The concentrations of select factors were measured in supernatants from untreated
      and cytokine-treated tissue explant cultures using ELISA. IL-1beta and TNF were
      applied as the stimuli. RESULTS: Paired samples of AAT and ScAT, obtained from
      the same patients, contained a similar number of macrophages, displaying an M2
      skewed phenotype. Both tissues released equivalent amounts of IL-1beta, TNF, IL
      10 and macrophage migration inhibitory factor (MIF). However, AAT secreted more
      chemokines (CCL2, CCL5), cytokines [IL-6, IL-8, IL-1 receptor antagonist (IL
      1Ra)], hepatocyte growth factor (HGF) and MMP-3 than ScAT. Basal secretion of
      adipocytokines was not patient specific. Except for HGF and MIF, cytokine
      treatment up-regulated the release of these factors from both tissues, but also
      upon stimulation AAT produced more IL-6, IL-8 and IL-1Ra than ScAT. CONCLUSION:
      The secretory activity, reflecting cell activation status but not phenotype or
      the number of macrophages, discriminates rheumatoid AAT from ScAT. By releasing
      various factors possessing chemotactic, proinflammatory, anti-inflammatory and
      tissue degrading activities, AAT resident macrophages may drive and control local
      pathological processes.

PMID- 24014648
TI  - Development of a colour Doppler ultrasound scoring system in patients of
      Takayasu's arteritis and its correlation with clinical activity score (ITAS
      2010).
AB  - OBJECTIVES: The objectives of this study were to develop a scoring system with
      colour Doppler ultrasound (CDUS) in patients with Takayasu's arteritis, to
      correlate the CDUS score with the Indian Takayasu's Activity Score (ITAS) and to
      assess the degree of agreement between CDUS and angiogram in the diagnosis of
      Takayasu's arteritis. METHODS: Nineteen angiographically confirmed Takayasu's
      arteritis patients fulfilling three or more of the 1990 ACR criteria were
      evaluated. Their ITASs were recorded. A CDUS scoring system, CDUS-Kolkata (CDUS
      K), was devised based on the presence of stenosis and altered flow patterns. It
      was then correlated with the ITAS. An inter-rater agreement analysis was done
      between the CDUS-K scores and angiographic scores in selected arterial sites.
      RESULTS: We found a significant degree of correlation between the ITAS and the
      CDUS-K score (r = 0.7144, 95% CI 0.3852, 0.8823, P = 0.0006). A high degree of
      correlation was found between the CDUS-K and angiographic scores in the selected
      arterial sites (kappa-value = 0.725 on inter-rater agreement analysis).
      CONCLUSION: CDUS imaging may be used as an objective tool for assessing disease
      severity in Takayasu's arteritis. Development of a CDUS-K scoring system would be
      a supplementary tool to clinical scoring and the ITAS. CDUS imaging could be a
      cost-effective, non-invasive and reliable substitute for angiogram, especially
      for follow-up in Takayasu's arteritis patients.

PMID- 24014649
TI  - Paediatric rheumatology practice in the UK benchmarked against the British
      Society for Paediatric and Adolescent Rheumatology/Arthritis and Musculoskeletal
      Alliance Standards of Care for juvenile idiopathic arthritis.
AB  - OBJECTIVE: To describe current clinical practice against the BSPAR/ARMA Standards
      of Care (SOCs) for children and young people (CYP) with incident JIA. METHODS:
      Ten UK paediatric rheumatology centres (including all current centres nationally
      accredited for paediatric rheumatology higher specialist training) participated
      in a retrospective case notes review using a pretested pro forma based on the
      SOC. Data collected per centre included clinical service configuration and the
      initial clinical care for a minimum of 30 consecutive new patients seen within
      the previous 2 years and followed up for at least 6 months. RESULTS: A total of
      428 CYP with JIA (median age 11 years, range 1-21 years) were included, with
      complete data available for 73% (311/428). Against the key SOCs, 41% (175/428)
      were assessed <=10 weeks from symptom onset, 60% (186/311) <=4 weeks from
      referral, 26% (81/311) had eye screening at <=6 weeks, 83% (282/341) had joint
      injections at <=6 weeks, 59% (184/311) were assessed by a nurse specialist at <=4
      weeks and 45% (141/311) were assessed by a physiotherapist at <=8 weeks. A median
      of 6% of patients per centre participated in clinical trials. All centres had
      access to eye screening and prescribed biologic therapies. All had access to a
      nurse specialist and physiotherapist. Most had access to an occupational
      therapist (8/10), psychologist (8/10), joint injection lists (general
      anaesthesia/inhaled analgesia) (9/10) and designated transitional care clinics
      (7/10). CONCLUSION: This first description of UK clinical practice in paediatric
      rheumatology benchmarked against the BSPAR/ARMA SOCs demonstrates variable
      clinical service delivery. Considerable delay in access to specialist care is
      evident and this needs to be addressed in order to improve clinical outcomes.

PMID- 24014651
TI  - Progesterone receptor and Stat5 signaling cross talk through RANKL in mammary
      epithelial cells.
AB  - Progesterone (P4) stimulates proliferation of the mammary epithelium by a
      mechanism that involves paracrine signaling mediated from progesterone receptor
      (PR)-positive to neighboring PR-negative cells. Here we used a primary mouse
      mammary epithelial cell (MEC) culture system to define the molecular mechanism by
      which P4 regulates the expression of target gene effectors of proliferation
      including the paracrine factor receptor and activator of nuclear factor kappaB
      ligand (RANKL). MECs from adult virgin mice grown and embedded in three
      dimensional basement-membrane medium resemble mammary ducts in vivo structurally
      and with respect to other properties including a heterogeneous pattern of PR
      expression, P4 induction of RANKL and other target genes in a PR-dependent
      manner, and a proliferative response to progestin. RANKL was demonstrated to have
      multiple functional P4-responsive enhancers that bind PR in a hormone-dependent
      manner as detected by chromatin immunoprecipitation assay. P4 also stimulated
      recruitment of signal transducer and activator of transcription (Stat)5a to RANKL
      enhancers through an apparent tethering with PR. Analysis of primary MECs from
      Stat5a knockout mice revealed that P4 induction of RANKL and a broad range of
      other PR target genes required Stat5a, as did P4-stimulated cell proliferation.
      In the absence of Stat5a, PR binding was lost at selective RANKL enhancers but
      was retained with others, suggesting that Stat5a acts to facilitate PR DNA
      binding at selective sites and to function as a coactivator with DNA-bound PR at
      others. These results show that RANKL is a direct PR target gene and that Stat5a
      has a novel role as a cofactor in PR-mediated transcriptional signaling in the
      mammary gland. 

PMID- 24014650
TI  - Regulation of iNOS gene transcription by IL-1beta and IFN-gamma requires a
      coactivator exchange mechanism.
AB  - The proinflammatory cytokines IL-1beta and IFN-gamma decrease functional islet
      beta-cell mass in part through the increased expression of specific genes, such
      as inducible nitric oxide synthase (iNOS). Dysregulated iNOS protein accumulation
      leads to overproduction of nitric oxide, which induces DNA damage, impairs beta
      cell function, and ultimately diminishes cellular viability. However, the
      transcriptional mechanisms underlying cytokine-mediated expression of the iNOS
      gene are not completely understood. Herein, we demonstrated that individual
      mutations within the proximal and distal nuclear factor-kappaB sites impaired
      cytokine-mediated transcriptional activation. Surprisingly, mutating IFN-gamma
      activated site (GAS) elements in the iNOS gene promoter, which are classically
      responsive to IFN-gamma, modulated transcriptional sensitivity to IL-1beta.
      Transcriptional sensitivity to IL-1beta was increased by generation of a
      consensus GAS element and decreased correspondingly with 1 or 2 nucleotide
      divergences from the consensus sequence. The nuclear factor-kappaB subunits p65
      and p50 bound to the kappaB response elements in an IL-1beta-dependent manner. IL
      1beta also promoted binding of serine-phosphorylated signal transducer and
      activator of transcription-1 (STAT1) (Ser727) but not tyrosine-phosphorylated
      STAT1 (Tyr701) to GAS elements. However, phosphorylation at Tyr701 was required
      for IFN-gamma to potentiate the IL-1beta response. Furthermore, coactivator p300
      and coactivator arginine methyltransferase were recruited to the iNOS gene
      promoter with concomitant displacement of the coactivator CREB-binding protein in
      cells exposed to IL-1beta. Moreover, these coordinated changes in factor
      recruitment were associated with alterations in acetylation, methylation, and
      phosphorylation of histone proteins. We conclude that p65 and STAT1 cooperate to
      control iNOS gene transcription in response to proinflammatory cytokines by a
      coactivator exchange mechanism. This increase in transcription is also associated
      with signal-specific chromatin remodeling that leads to RNA polymerase II
      recruitment and phosphorylation. 

PMID- 24014652
TI  - Lack of P-glycoprotein-mediated efflux and the potential involvement of an influx
      transport process contributing to the intestinal uptake of deltamethrin, cis
      permethrin, and trans-permethrin.
AB  - The effectiveness and widespread use of pyrethroid insecticides has lead to
      concerns regarding their safety. Human ingestion of these potentially neurotoxic
      compounds is typically through hand-to-mouth contact or consumption of
      contaminated foods. A substantial proportion of ingested pyrethroids are
      eliminated in feces, suggesting that absorption is limited, possibly by the
      action of the efflux transporter P-glycoprotein (P-gp). We utilized caco-2 cells
      as a model system for intestinal enterocytes and qualitatively and quantitatively
      assessed the transport of deltamethrin (DLM), cis-permethrin (CPM), and trans
      permethrin (TPM). Caco-2 cell uptake of the P-gp substrate R6G was increased by
      the P-gp inhibitors cyclosporine A (CSA) and ritonavir but not by DLM, CPM, and
      TPM. Unexpectedly, CSA and ritonavir significantly reduced the uptake of DLM,
      CPM, and TPM. Permeability coefficients (P app) and directional flux of DLM, CPM,
      or TPM were greater in the absorptive than the secretory (efflux) direction when
      measured across caco-2 monolayers grown on Transwell inserts. When CSA was
      applied to the monolayers' apical (AP) side, the AP to basolateral (BL) P app was
      significantly reduced, with no change in the BL to AP P app. Kinetic analysis
      demonstrated saturable transport kinetics for all 3 pyrethroids. These findings
      indicate that the cellular uptake of DLM, CPM, and TPM is not limited by P-gp
      efflux but undergo absorptive influx transport as a contributing mechanism for
      cellular uptake. However, the overall P app values for DLM, CPM, and TPM are
      consistent with the low permeability/low absorption compound mannitol, suggesting
      limited gastrointestinal absorption potential.

PMID- 24014656
TI  - Differentiation of PCV1 and PCV2 by a multiplex real-time PCR assay.

PMID- 24014653
TI  - Structure-activity relationship of selected meta- and para-hydroxylated non
      dioxin like polychlorinated biphenyls: from single RyR1 channels to muscle
      dysfunction.
AB  - Non-dioxin like polychlorinated biphenyls (NDL-PCBs) are legacy environmental
      contaminants with contemporary unintentional sources. NDL-PCBs interact with
      ryanodine receptors (RyRs), Ca(2+) channels of sarcoplasmic/endoplasmic reticulum
      (SR/ER) that regulate excitation-contraction coupling (ECC) and Ca(2+)-dependent
      cell signaling in muscle. Activities of 4 chiral congeners PCB91, 95, 132, and
      149 and their respective 4- and 5-hydroxy (-OH) derivatives toward rabbit
      skeletal muscle ryanodine receptor (RyR1) are investigated using [(3)H]ryanodine
      binding and SR Ca(2+) flux analyses. Although 5-OH metabolites have comparable
      activity to their respective parent in both assays, 4-OH derivatives are unable
      to trigger Ca(2+) release from SR microsomes in the presence of Ca(2+)-ATPase
      activity. PCB95 and derivatives are investigated using single channel voltage
      clamp and primary murine embryonic muscle cells (myotubes). Like PCB95, 5-OH
      PCB95 quickly and persistently increases channel open probability (p o > .9) by
      stabilizing the full-open channel state, whereas 4-OH-PCB95 transiently enhances
      p o. Ca(2+) imaging of myotubes loaded with Fluo-4 show that acute exposure to
      PCB95 (5 uM) potentiates ECC and caffeine responses and partially depletes SR
      Ca(2+) stores. Exposure to 5-OH-PCB95 (5 uM) increases cytoplasmic Ca(2+),
      leading to rapid ECC failure in 50% of myotubes with the remainder retaining
      negligible responses. 4-OH-PCB95 neither increases baseline Ca(2+) nor causes ECC
      failure but depresses ECC and caffeine responses by 50%. With longer (3h)
      exposure to 300 nM PCB95, 5-OH-PCB95, or 4-OH-PCB95 decreases the number of ECC
      responsive myotubes by 22%, 81%, and 51% compared with control by depleting SR
      Ca(2+) and/or uncoupling ECC. NDL-PCBs and their 5-OH and 4-OH metabolites
      differentially influence RyR1 channel activity and ECC in embryonic skeletal
      muscle.

PMID- 24014657
TI  - The prevalence of sarcopenia in very old individuals according to the European
      consensus definition: insights from the BELFRAIL study.
AB  - BACKGROUND: the prevalence of sarcopenia varies widely between studies. The
      objective of this study was to assess the prevalence of sarcopenia in a
      representative sample of persons aged 80 years and older according to the
      European Working Group on Sarcopenia in Older People (EWGSOP) algorithm and the
      proposed cut-off values. A secondary aim was to investigate the relationship
      between different individual criteria and low physical performance capacity.
      METHODS: baseline data of the prospective BELFRAIL study (BFC80+) were analysed.
      Sarcopenia status was determined according to the EWGSOP guidelines. The skeletal
      muscle mass index (SMI) was assessed according to bioelectrical impedance. Muscle
      strength and muscle performance were evaluated according to grip strength and the
      modified short physical performance battery (SPPBm). A logistic regression
      analysis was performed. RESULTS: according to the EWGSOP algorithm, 12.5% of the
      participants were classified in the sarcopenia group. Sixty percent of the female
      participants had muscle strength values below the cut-off and 70% had low SPPBm
      values. In males, these prevalence values were 49.5% for grip strength and 39.7%
      for SPPB. The logistic regression analysis showed that low SPPBm was associated
      with grip strength (OR: 0.88, 95% CI: 0.84-0.92) independent of SMI. CONCLUSION:
      in a population-based sample of the very old the prevalence of sarcopenia
      according to the EWGSOP algorithm is similar to the prevalence of sarcopenia with
      SMI as a single criterion. A large number of participants with a sufficient SMI
      value showed low muscle strength and/or a poor SPPBm score. A low SPPBm was
      associated with grip strength but not with SMI.

PMID- 24014658
TI  - Passive immunization against marinobufagenin attenuates renal fibrosis and
      improves renal function in experimental renal disease.
AB  - BACKGROUND: We have shown that the cardiotonic steroid marinobufagenin (MBG) is
      elevated in clinical and experimental renal disease, and significantly
      contributes to the development of experimental uremic cardiomyopathy induced by
      removal of five-sixths of the kidney (5/6 nephrectomy; PNx) in the rat. We have
      demonstrated that both active and passive immunization against MBG with an anti
      MBG monoclonal antibody (mAb 3E9) significantly attenuated cardiac fibrosis
      following PNx. In the present study we sought to determine whether the use of mAb
      3E9 could improve renal function following PNx. METHODS: Sprague-Dawley rats were
      treated with either mAb 3E9 or with DigiFab (an affinity-purified anti-digoxin
      antibody formerly named Digibind) during the fourth week after PNx. Sham-operated
      animals and PNx animals treated with an IgG antibody served as controls. Plasma,
      urine, and renal tissue were collected at the completion of the study to
      determine the effects of antibody treatment on renal function. RESULTS: In PNx
      rats, treatments with mAb 3E9 and DigiFab, respectively, significantly reduced
      plasma creatinine, improved creatinine clearance, and reduced proteinuria below
      the values of these three measures in IgG-treated PNx controls. Additionally,
      treatment with mAb 3E9 and DigiFab significantly reduced renal fibrosis as
      measured with Western blotting and Sirius red/Fast green staining. CONCLUSIONS:
      Passive immunization against MBG significantly improved renal function and
      markedly reduced renal fibrosis following the experimental induction of renal
      disease. The work in the study reported here adds to a growing body of knowledge
      implicating MBG in the development of chronic renal disease. Passive immunization
      against cardiotonic steroids may serve as a promising treatment for chronic renal
      disease.

PMID- 24014660
TI  - Osmotic stress adaptation in Lactobacillus casei BL23 leads to structural changes
      in the cell wall polymer lipoteichoic acid.
AB  - The probiotic Gram-positive bacterium Lactobacillus casei BL23 is naturally
      confronted with salt-stress habitats. It has been previously reported that growth
      in high-salt medium, containing 0.8 M NaCl, leads to modifications in the cell
      envelope of this bacterium. In this study, we report that L. casei BL23 has an
      increased ability to form biofilms and to bind cations in high-salt conditions.
      This behaviour correlated with modifications of surface properties involving
      teichoic acids, which are important cell wall components. We also showed that, in
      these high-salt conditions, L. casei BL23 produces less of the cell wall polymer
      lipoteichoic acid (LTA), and that this anionic polymer has a shorter mean chain
      length and a lower level of d-alanyl-substitution. Analysis of the transcript
      levels of the dltABCD operon, encoding the enzymes required for the incorporation
      of d-alanine into anionic polymers, showed a 16-fold reduction in mRNA levels,
      which is consistent with a decrease in d-alanine substitutions on LTA.
      Furthermore, a 13-fold reduction in the transcript levels was observed for the
      gene LCABL_09330 coding for a putative LTA synthase. To provide further
      experimental evidence that LCABL_09330 is a true LTA synthase (LtaS) in L. casei
      BL23, the enzymic domain was cloned and expressed in E. coli. The purified
      protein was able to hydrolyse the membrane lipid phosphatidylglycerol as expected
      for an LTA synthase enzyme, and hence LCABL_09330 was renamed LtaS. The purified
      enzyme showed Mn(2+)-ion dependent activity, and its activity was modulated by
      differences in NaCl concentration. The decrease in both ltaS transcript levels
      and enzyme activity observed in high-salt conditions might influence the length
      of the LTA backbone chain. A putative function of the modified LTA structure is
      discussed that is compatible with the growth under salt-stress conditions and
      with the overall envelope modifications taking place during this stress
      condition. 

PMID- 24014659
TI  - Effect of dietary pulses on blood pressure: a systematic review and meta-analysis
      of controlled feeding trials.
AB  - BACKGROUND: Current guidelines recommend diet and lifestyle modifications for
      primary prevention and treatment of hypertension, but do not encourage dietary
      pulses specifically for lowering blood pressure (BP). To quantify the effect of
      dietary pulse interventions on BP and provide evidence for their inclusion in
      dietary guidelines, a systematic review and meta-analysis of controlled feeding
      trials was conducted. METHODS: MEDLINE, EMBASE, Cochrane Library, and CINAHL were
      each searched from inception through 5 May 2013. Human trials >=3 weeks that
      reported data for systolic, diastolic, and/or mean arterial BPs were included.
      Two reviewers independently extracted data and assessed methodological quality
      and risk of bias of included studies. Effect estimates were pooled using random
      effects models, and reported as mean differences (MD) with 95% confidence
      intervals (CIs). Heterogeneity was assessed (chi(2) test) and quantified (I(2)).
      RESULTS: Eight isocaloric trials (n = 554 participants with and without
      hypertension) were included in the analysis. Dietary pulses, exchanged
      isocalorically for other foods, significantly lowered systolic (MD = -2.25 mm Hg
      (95% CI, -4.22 to -0.28), P = 0.03) and mean arterial BP (MD = -0.75 mm Hg (95%
      CI, -1.44 to -0.06), P = 0.03), and diastolic BP non-significantly (MD = -0.71 mm
      Hg (95% CI, -1.74 to 0.31), P = 0.17). Heterogeneity was significant for all
      outcomes. CONCLUSIONS: Dietary pulses significantly lowered BP in people with and
      without hypertension. Higher-quality large-scale trials are needed to support
      these findings. CLINICAL TRIAL REGISTRATION: NCT01594567.

PMID- 24014661
TI  - Insertion site and distribution of a genomic island conferring DNA
      phosphorothioation in the Mycobacterium abscessus complex.
AB  - Nearly half of US clinical isolates of the emerging pathogen Mycobacterium
      abscessus were reported to exhibit smeared DNA during PFGE. This DNA degradation
      (Dnd) phenotype results from DNA phosphorothioation, a sulfur modification found
      in other bacteria and conferred by dnd genes located on mobile elements. Putative
      dnd genes are located on a 19.6 kbp genomic island (GI) in the M. abscessus type
      strain ATCC 19977. We confirmed that ATCC 19977(T) is Dnd-positive by PFGE and we
      developed a PCR assay to predict Dnd phenotype. Dnd-positive strains generated an
      amplicon from dndC whereas Dnd-negative strains generated a bridge amplicon that
      spanned the GI insertion site, indicating they lacked the entire 'Dnd-GI'.
      Comparative analyses of sequences from the bridge amplicon with ATCC 19977(T)
      revealed the Dnd-GI is flanked by 22 bp repeats in M. abscessus sensu stricto and
      inserted downstream of a tRNA-Ala gene and between inverted repeats. Regions
      flanking the Dnd-GI were highly conserved within the M. abscessus complex.
      Bioinformatics studies suggest the Dnd-GI inserted independently into a strain of
      Mycobacterium massiliense and that other species of mycobacteria also have dnd
      genes, supporting reports that the Dnd phenotype is common among actinomycetes.
      Within the M. abscessus complex, Dnd-positive clinical isolates were primarily M.
      abscessus sensu stricto, and tandem repeat typing indicated these isolates were
      highly related, confirming previous PFGE studies and revealing a widespread
      family of strains with significance in human disease. 

PMID- 24014662
TI  - The WbaK acetyltransferase of Salmonella enterica group E gives insights into O
      antigen evolution.
AB  - O antigens are polysaccharides consisting of repeat units of three to eight
      sugars, generally assembled by genes in a discrete O antigen gene cluster.
      Salmonella enterica produces 46 forms of O antigen, and most of the variation is
      determined by genes in the gene cluster. However in some cases the structures are
      modified by enzymes encoded outside of the gene cluster, and several such
      modifications have been reported for Salmonella enterica group E, some with the
      genes on bacteriophages and one gene at a distant chromosomal site. We identified
      the enzyme, WbaK, that is responsible for O-acetylating the subgroup E1 O
      antigen, and found that the gene is located just downstream of the gene cluster
      as currently known. The wbaK gene appears to have been imported by a
      recombination event that also replaced the last 37 bp of the wbaP gene,
      indicating that homologous recombination was involved. Some of the group E
      strains we studied must have the original gene cluster, as they lack wbaK and the
      sequence downstream of wbaP is very similar to that in several other S. enterica
      O antigen gene clusters. In effect the gene cluster was extended by one gene in
      subgroup E1. It appears that a function that is usually encoded by a gene outside
      of the gene cluster has been added to the gene cluster, in this case giving an
      example of how such gene clusters can evolve. 

PMID- 24014663
TI  - Conformational folding of mycobacterial methoxy- and ketomycolic acids
      facilitated by alpha-methyl trans-cyclopropane groups rather than cis
      cyclopropane units.
AB  - The oxygenated long-chain mycolic acids from many mycobacteria are characterized
      by the presence of mid-chain cyclopropane groups, which can have either cis
      configuration or trans-configuration with an adjacent methyl branch. To determine
      the effect of these functional groups on mycolic acid conformation, surface
      pressure (pi) versus mean molecular area isotherms of methoxy- (MeO-) mycolic
      acids (MAs) from Mycobacterium kansasii, Mycobacterium tuberculosis (Mtb) Canetti
      and Mtb H37Ra, and of keto-MAs from Mycobacterium avium-intracellulare complex
      (MAC) and Mtb H37Ra were recorded and analysed. The MeO- and keto-MAs from Mtb
      H37Ra, containing scarcely any trans-cyclopropyl groups, apparently took no fully
      folded 'W-form' conformations. Keto-MA from MAC, whose trans-cyclopropyl group
      content is nearly 90 %, showed a very solid W-form conformation. MeO-MAs from M.
      kansasii and Mtb Canetti gave stable W-form conformations at lower temperatures
      and surface pressures and extended conformations at higher temperatures and
      surface pressures; their W-form conformation was not as stable as expected from
      their cis-cyclopropyl group content, probably because they had a wide range of
      constituent homologues. Energy level calculations of cis- or alpha-methyl trans
      cyclopropane-containing model molecules and computer simulation studies confirmed
      the superior folding properties of the latter functional unit. The present
      results were compared with those of MeO- and keto-MAs from Mtb and from M. bovis
      Bacillus Calmette-Guerin (BCG) reported previously. Among the oxygenated MAs,
      those having higher trans-cyclopropane content tended to take W-form
      conformations more firmly, implying that the meromycolate proximal intra-chain
      alpha-methyl trans-cyclopropane groups facilitated MA folding more than cis
      cyclopropane groups. 

PMID- 24014664
TI  - Modulation of gene expression by Pseudomonas aeruginosa during chronic infection
      in the adult cystic fibrosis lung.
AB  - Chronic Pseudomonas aeruginosa infection is the leading cause of morbidity and
      mortality in cystic fibrosis (CF) patients. P. aeruginosa isolates undergo
      significant transcriptomic and proteomic modulation as they adapt to the niche
      environment of the CF lung and the host defences. This study characterized the in
      vitro virulence of isogenic strain pairs of P. aeruginosa epidemic or frequent
      clonal complexes (FCCs) and non-epidemic or infrequent clonal complexes (IFCCs)
      that were collected 5-8 years apart from five chronically infected adult CF
      patients. Strains showed a significant decrease in virulence over the course of
      chronic infection using a Caenorhabditis elegans slow-killing assay and in
      phenotypic tests for important virulence factors. This decrease in virulence
      correlated with numerous differentially expressed genes such as oprG, lasB, rsaL
      and lecB. Microarray analysis identified a large genomic island deletion in the
      IFCC strain pair that included type three secretion system effector and fimbrial
      subunit genes. This study presents novel in vitro data to examine the
      transcriptomic profiles of sequentially collected P. aeruginosa from CF adults.
      The genes with virulence-related functions identified here present potential
      targets for new therapies and vaccines against FCCs and IFCCs. 

PMID- 24014665
TI  - Francisella tularensis subsp. holarctica DsbA homologue: a thioredoxin-like
      protein with chaperone function.
AB  - Francisella tularensis is a highly infectious facultative intracellular bacterium
      and aetiological agent of tularaemia. The conserved hypothetical lipoprotein with
      homology to thiol/disulphide oxidoreductase proteins (FtDsbA) is an essential
      virulence factor in F. tularensis. Its protein sequence has two different
      domains: the DsbA_Com1_like domain (DSBA), with the highly conserved
      catalytically active site CXXC and cis-proline residue; and the domain amino
      terminal to FKBP-type peptidyl-prolyl isomerases (FKBP_N). To establish the role
      of both domains in tularaemia infection models, site-directed and deletion
      mutagenesis affecting the active site (AXXA), the cis-proline (P286T) and the
      FKBP_N domain (DeltaFKBP_N) were performed. The generated mutations led to high
      attenuation with the ability to induce full or partial host protective immunity.
      Recombinant protein analysis revealed that the active site CXXC as well as the
      cis-proline residue and the FKBP_N domain are necessary for correct
      thiol/disulphide oxidoreductase activity. By contrast, only the DSBA domain (and
      not the FKBP_N domain) seems to be responsible for the in vitro chaperone
      activity of the FtDsbA protein. 

PMID- 24014666
TI  - A synthetic system for expression of components of a bacterial microcompartment.
AB  - In general, prokaryotes are considered to be single-celled organisms that lack
      internal membrane-bound organelles. However, many bacteria produce proteinaceous
      microcompartments that serve a similar purpose, i.e. to concentrate specific
      enzymic reactions together or to shield the wider cytoplasm from toxic metabolic
      intermediates. In this paper, a synthetic operon encoding the key structural
      components of a microcompartment was designed based on the genes for the
      Salmonella propanediol utilization (Pdu) microcompartment. The genes chosen
      included pduA, -B, -J, -K, -N, -T and -U, and each was shown to produce protein
      in an Escherichia coli chassis. In parallel, a set of compatible vectors designed
      to express non-native cargo proteins was also designed and tested. Engineered
      hexa-His tags allowed isolation of the components of the microcompartments
      together with co-expressed, untagged, cargo proteins. Finally, an in vivo
      protease accessibility assay suggested that a PduD-GFP fusion could be protected
      from proteolysis when co-expressed with the synthetic microcompartment operon.
      This work gives encouragement that it may be possible to harness the genes
      encoding a non-native microcompartment for future biotechnological applications. 

PMID- 24014668
TI  - Expansion of the piriform cortex contributes to corticothalamic pathfinding
      defects in Gli3 conditional mutants.
AB  - The corticothalamic and thalamocortical tracts play essential roles in the
      communication between the cortex and thalamus. During development, axons forming
      these tracts have to follow a complex path to reach their target areas. While
      much attention has been paid to the mechanisms regulating their passage through
      the ventral telencephalon, very little is known about how the developing cortex
      contributes to corticothalamic/thalamocortical tract formation. Gli3 encodes a
      zinc finger transcription factor widely expressed in telencephalic progenitors
      which has important roles in corticothalamic and thalamocortical pathfinding.
      Here, we conditionally inactivated Gli3 in dorsal telencephalic progenitors to
      determine its role in corticothalamic tract formation. In Emx1Cre;Gli3(fl/fl)
      mutants, only a few corticothalamic axons enter the striatum in a restricted
      dorsal domain. This restricted entry correlates with a medial expansion of the
      piriform cortex. Transplantation experiments showed that the expanded piriform
      cortex repels corticofugal axons. Moreover, expression of Sema5B, a
      chemorepellent for corticofugal axons produced by the piriform cortex, is
      similarly expanded. Finally, time course analysis revealed an expansion of the
      ventral pallial progenitor domain which gives rise to the piriform cortex. Hence,
      control of lateral cortical development by Gli3 at the progenitor level is
      crucial for corticothalamic pathfinding. 

PMID- 24014669
TI  - Cortical and subcortical connections of the human claustrum revealed in vivo by
      constrained spherical deconvolution tractography.
AB  - The claustrum is a thin layer of gray matter that is at the center of an active
      scientific debate. Recently, Constrained Spherical Deconvolution (CSD)
      tractography has proved to be an extraordinary tool allowing to track white
      matter fibers from cortex to cortical and subcortical targets with subvoxel
      resolution. The aim of this study was to evaluate claustral connectivity in the
      human brain. Ten normal brains were analyzed by using the High Angular Resolution
      Diffusion Imaging CSD-based technique. Tractography revealed 4 groups of white
      matter fibers connecting the claustrum with the brain cortex: Anterior,
      posterior, superior, and lateral. The anterior and posterior cortico-claustral
      tracts connected the claustrum to prefrontal cortex and visual areas. The
      superior tract linked the claustrum with sensory-motor areas, while the lateral
      pathway connected the claustrum to the auditory cortex. In addition, we
      demonstrated a claustral medial pathway connecting the claustrum with the basal
      ganglia, specifically with caudate nucleus, putamen, and globus pallidus. An
      interesting and exciting new finding was the demonstration of a bilateral
      connection between claustrum and contralateral cortical areas and a well
      represented interclaustral communication with interconnection bundles
      interspersed within the bulk of the trunk of the corpus callosum. The
      physiological and pathophysiological relevance of these findings are discussed. 

PMID- 24014670
TI  - Correlated gene expression and target specificity demonstrate excitatory
      projection neuron diversity.
AB  - The neocortex contains diverse populations of excitatory neurons segregated by
      layer and further definable by their specific cortical and subcortical projection
      targets. The current study describes a systematic approach to identify molecular
      correlates of specific projection neuron classes in mouse primary somatosensory
      cortex (S1), using a combination of in situ hybridization (ISH) data mining,
      marker gene colocalization, and combined retrograde labeling with ISH for layer
      specific marker genes. First, we identified a large set of genes with specificity
      for each cortical layer, and that display heterogeneous patterns within those
      layers. Using these genes as markers, we find extensive evidence for the
      covariation of gene expression and projection target specificity in layer 2/3, 5,
      and 6, with individual genes labeling neurons projecting to specific subsets of
      target structures. The combination of gene expression and target specificity
      imply a great diversity of projection neuron classes that is similar to or
      greater than that of GABAergic interneurons. The covariance of these 2 phenotypic
      modalities suggests that these classes are both discrete and genetically
      specified. 

PMID- 24014671
TI  - Is there diurnal variation of the vestibulosympathetic reflex: implications for
      orthostatic hypotension.
AB  - Incidences of adverse cardiac events and orthostatic hypotension are associated
      with diurnal variations. The primary purpose of the present study was to
      determine if the vestibulosympathetic reflex (VSR) follows a diurnal variation in
      humans. We hypothesized that the VSR would be attenuated at night based on the
      relation between melatonin and the VSR. Arterial blood pressure, heart rate, calf
      blood flow, and muscle sympathetic nerve activity (MSNA) were measured in nine
      healthy subjects (28 +/- 1 yr, 5 men and 4 women) at rest and during head-down
      rotation. Each subject was tested during the day at 11:34 +/- 13 and again at
      night 22:10 +/- 5. MSNA was significantly decreased at night compared with day (8
      +/- 1 vs. 11 +/- 2 bursts/min, respectively, P < 0.02). Heart rate and arterial
      blood pressure at rest were significantly increased at night compared with day
      (heart rate: 70 +/- 4 vs. 66 +/- 4 beats/min and mean arterial blood pressure: 91
      +/- 2 vs. 87 +/- 1 mmHg, respectively). MSNA and hemodynamic responses to head
      down rotation were not significantly altered at night compared with day (changes
      of 3 +/- 1 bursts/min and 25 +/- 6% for MSNA and calf blood flow, respectively).
      The data indicate that MSNA at rest decreases during the late evening hours and
      exhibits a diurnal variation, whereas the VSR does not. In summary, diurnal
      variation of orthostatic hypotension in humans does not appear to be associated
      with changes in the VSR and MSNA at rest.

PMID- 24014672
TI  - Upregulation of heme oxygenase-1 potentiates EDH-type relaxations in the
      mesenteric artery of the spontaneously hypertensive rat.
AB  - Heme oxygenase (HO) converts heme to carbon monoxide, bilirubin, and free iron.
      The present study investigated whether or not HO-1 induction improves vascular
      relaxations attributable to endothelium-dependent hyperpolarization (EDH). Thirty
      six-week-old spontaneously hypertensive rats were treated with the HO-1 inducer
      hemin, the HO inhibitor zinc protoporphyrin IX (II) (ZnPP), the antioxidant
      apocynin, or combinations of these compounds. Isolated mesenteric arteries were
      prepared for measurement of isometric tension, protein presence, and production
      of reactive oxygen species (ROS). Hemin potentiated acetylcholine-evoked EDH-type
      relaxations in the presence of N(omega)-nitro-L-arginine methyl ester (l-NAME)
      and indomethacin, while the combined treatment with ZnPP plus hemin prevented
      these improvements. The intermediate conductance Ca(2+)-activated K(+) channel
      (IKCa) blocker TRAM-34 and the Na(+)-K(+)-ATPase blocker ouabain significantly
      impaired these hemin-potentiated relaxations. NS309-induced TRAM-34- and ouabain
      sensitive relaxations were enhanced by hemin. K(+)-induced ouabain-sensitive
      relaxations and the expression of Na(+)-K(+)-ATPase were increased by hemin. Thus
      HO-1 induction improves EDH-type relaxations by augmented activation of IKCa and
      the downstream Na(+)-K(+)-ATPase. Treatment with apocynin showed a similar effect
      as hemin in impairing ROS production, enhancing K(+)-induced relaxations, and
      increasing Na(+)-K(+)-ATPase expression, without affecting the expression of HO
      1. The effects of hemin and apocynin were not additive. These observations
      suggest that the effect of HO-1 induction on EDH-type relaxations is possibly due
      to its antioxidant properties. In vitro treatment with bilirubin, but not carbon
      monoxide, enhanced EDH-type relaxations and K(+)-induced ouabain-sensitive
      relaxations, suggesting that the production of bilirubin may be also involved.
      The present findings reveal that HO-1 may be a potential vascular-specific
      therapeutic strategy for endothelial dysfunction in hypertension.

PMID- 24014673
TI  - Attenuated muscle metaboreflex-induced increases in cardiac function in
      hypertension.
AB  - Sympathoactivation may be excessive during exercise in subjects with
      hypertension, leading to increased susceptibility to adverse cardiovascular
      events, including arrhythmias, infarction, stroke, and sudden cardiac death. The
      muscle metaboreflex is a powerful cardiovascular reflex capable of eliciting
      marked increases in sympathetic activity during exercise. We used conscious,
      chronically instrumented dogs trained to run on a motor-driven treadmill to
      investigate the effects of hypertension on the mechanisms of the muscle
      metaboreflex. Experiments were performed before and 30.9 +/- 4.2 days after
      induction of hypertension, which was induced via partial, unilateral renal artery
      occlusion. After induction of hypertension, resting mean arterial pressure was
      significantly elevated from 98.2 +/- 2.6 to 141.9 +/- 7.4 mmHg. The hypertension
      was caused by elevated total peripheral resistance. Although cardiac output was
      not significantly different at rest or during exercise after induction of
      hypertension, the rise in cardiac output with muscle metaboreflex activation was
      significantly reduced in hypertension. Metaboreflex-induced increases in left
      ventricular function were also depressed. These attenuated cardiac responses
      caused a smaller metaboreflex-induced rise in mean arterial pressure. We conclude
      that the ability of the muscle metaboreflex to elicit increases in cardiac
      function is impaired in hypertension, which may contribute to exercise
      intolerance.

PMID- 24014674
TI  - Recording sympathetic nerve activity chronically in rats: surgery techniques,
      assessment of nerve activity, and quantification.
AB  - The sympathetic nervous system plays a pivotal role in homeostasis through its
      direct innervation and functional impact on a variety of end organs. In rats, a
      number of methods are available to assess sympathetic nervous system function.
      Traditionally, direct recording of sympathetic nerve activity (SNA) has been
      restricted to acute, anesthetized preparations or conscious animals within a few
      days after electrode implantation. However, these approaches provide short-term
      data in studies designed to investigate changes in SNA during chronic disease
      states. Over the last several years, chronic SNA recording has been pioneered in
      rabbits and more recently in rats. The purpose of this article is to provide
      insights and a "how to" guide for chronic SNA recordings in rats based on
      experiences from two independent laboratories. We will present common
      methodologies used to chronically record SNA, characteristics and methods to
      distinguish sympathetic bursts versus electrical artifacts (and provide
      corresponding audio clips when available), and provide suggestions for analysis
      and presentation of data. In many instances, these same guidelines are applicable
      to acute SNA recordings. Using the surgical approaches described herein, both
      laboratories have been able to chronically record SNA in >50% of rats for a
      duration >3 wk. The ability to record SNA over the time course of several weeks
      will, undoubtedly, greatly impact the field of autonomic and cardiovascular
      physiology.

PMID- 24014676
TI  - Hemodynamic effects of implanting a unidirectional valve in the inferior vena
      cava of the Fontan circulation pathway: an in vitro investigation.
AB  - The Fontan surgical procedure used for treating patients with single ventricle
      congenital heart disorders results in a total cavopulmonary connection (TCPC) of
      the vena cavae to the pulmonary arteries (PAs). Sluggish TCPC flow and elevated
      hepatic venous pressures are commonly observed in this altered physiology, which
      in turn can lead to long-term complications including liver congestion and
      cirrhosis. The hypothesis of this study is that placement of a unidirectional
      valve within the inferior vena cava (IVC) will improve hemodynamics of the Fontan
      circulation by preventing retrograde flow and lowering hepatic venous pressure.
      An in vitro experimental setup consisting of an idealized TCPC model with
      flexible walls was used for investigation, and a bovine venous valve was inserted
      in the IVC below the TCPC. Pressure fluctuations were introduced in the flow
      through the model to simulate venous pulsatility. Hemodynamics of baseline and
      valve-implanted conditions were compared across total caval flows ranging from
      1.0 to 2.5 l/min with varying caval flow distributions. The results indicated
      that valve closure occurred for 15-20% of the total cycle, with consequent
      reduction in the upstream hepatic venous pressure by 5 to 10 mmHg. Energy loss
      (EL) through the TCPC was lowered with valve implantation to 20-50% of baseline,
      occurring across all flow conditions considered with mean caval and PA pressures
      greater than 10 mmHg. The results of this in vitro modeling suggest that IVC
      valve placement has the potential to improve hemodynamics in the Fontan
      circulation by decreasing hepatic venous hypertension and EL.

PMID- 24014675
TI  - Sympathetic cardiac hyperinnervation and atrial autonomic imbalance in diet
      induced obesity promote cardiac arrhythmias.
AB  - Obesity increases the risk of arrhythmias and sudden cardiac death, but the
      mechanisms are unknown. This study tested the hypothesis that obesity-induced
      cardiac sympathetic outgrowth and hyperinnervation promotes the development of
      arrhythmic events. Male Sprague-Dawley rats (250-275 g), fed a high-fat diet (33%
      kcal/fat), diverged into obesity-resistant (OR) and obesity-prone (OP) groups and
      were compared with rats fed normal chow (13% kcal/fat; CON). In vitro experiments
      showed that both OR and OP rats exhibited hyperinnervation of the heart and high
      sympathetic outgrowth compared with CON rats, even though OR rats are not obese.
      Despite the hyperinnervation and outgrowth, we showed that, in vivo, OR rats were
      less susceptible to arrhythmic events after an intravenous epinephrine challenge
      compared with OP rats. On examining total and stimulus-evoked neurotransmitter
      levels in an ex vivo system, we demonstrate that atrial acetylcholine content and
      release were attenuated in OP compared with OR and CON groups. OP rats also
      expressed elevated atrial norepinephrine content, while norepinephrine release
      was suppressed. These findings suggest that the consumption of a high-fat diet,
      even in the absence of overt obesity, stimulates sympathetic outgrowth and
      hyperinnervation of the heart. However, normalized cardiac parasympathetic
      nervous system control may protect the heart from arrhythmic events.

PMID- 24014677
TI  - Cyclooxygenase-1 inhibition attenuates angiotensin II-salt hypertension and
      neurogenic pressor activity in the rat.
AB  - Cyclooxygenase (COX)-derived prostanoids contribute to angiotensin II (ANG II)
      hypertension (HTN). However, the specific mechanisms by which prostanoids act are
      unclear. ANG II-induced HTN is caused partly by increased sympathetic nervous
      system activity, especially in a setting of high dietary salt intake. This study
      tested the hypothesis that COX-derived prostanoids cause ANG II-salt
      sympathoexcitation and HTN. Experiments were conducted in conscious rats.
      Infusion of ANG II (150 ng.kg(-1).min(-1) sc) caused a marked HTN in rats on 2%
      salt diet, but a much smaller increase in blood pressure in rats on 0.4% salt
      diet. The nonselective COX inhibitor ketoprofen (2 mg/kg sc) given throughout the
      ANG-II infusion period attenuated HTN development in rats on 2% NaCl diet, but
      not in rats on 0.4% NaCl diet. The acute depressor response to ganglion blockade
      was used to assess neurogenic pressor activity in rats on 2% NaCl diet.
      Ketoprofen-treated rats showed a smaller fall in arterial pressure in response to
      ganglion blockade during ANG-II infusion than did nontreated controls. In
      additional experiments, ketoprofen-treated rats exhibited smaller increases in
      plasma norepinephrine levels and whole body norepinephrine spillover than we
      previously reported in ANG II-salt HTN. Finally, the effects of the selective COX
      1 inhibitor SC560 (10 mg.kg(-1).day(-1) ip) and the selective COX-2 inhibitor
      nimesulide (10 mg.kg(-1).day(-1) ip) were investigated. Treatment with SC560 but
      not nimesulide significantly reduced blood pressure and the depressor response to
      ganglion blockade in ANG II-salt HTN rats. The results suggest that COX-1
      products are critical for sympathoexcitation and the full development of ANG II
      salt HTN in rats.

PMID- 24014678
TI  - COX-1-derived PGE2 and PGE2 type 1 receptors are vital for angiotensin II-induced
      formation of reactive oxygen species and Ca(2+) influx in the subfornical organ.
AB  - Regulation of blood pressure by angiotensin II (ANG II) is a process that
      involves the reactive oxygen species (ROS) and calcium. We have shown that ANG-II
      type 1 receptor (AT1R) and prostaglandin E2 (PGE2) type 1 receptors (EP1R) are
      required in the subfornical organ (SFO) for ROS-mediated hypertension induced by
      slow-pressor ANG-II infusion. However, the signaling pathway associated with this
      process remains unclear. We sought to determine mechanisms underlying the ANG II
      induced ROS and calcium influx in mouse SFO cells. Ultrastructural studies showed
      that cyclooxygenase 1 (COX-1) codistributes with AT1R in the SFO, indicating
      spatial proximity. Functional studies using SFO cells revealed that ANG II
      potentiated PGE2 release, an effect dependent on AT1R, phospholipase A2 (PLA2)
      and COX-1. Furthermore, both ANG II and PGE2 increased ROS formation. While the
      increase in ROS initiated by ANG II, but not PGE2, required the activation of the
      AT1R/PLA2/COX-1 pathway, both ANG II and PGE2 were dependent on EP1R and Nox2 as
      downstream effectors. Finally, ANG II potentiated voltage-gated L-type Ca(2+)
      currents in SFO neurons via the same signaling pathway required for PGE2
      production. Blockade of EP1R and Nox2-derived ROS inhibited ANG II and PGE2
      mediated Ca(2+) currents. We propose a mechanism whereby ANG II increases COX-1
      derived PGE2 through the AT1R/PLA2 pathway, which promotes ROS production by
      EP1R/Nox2 signaling in the SFO. ANG II-induced ROS are coupled with Ca(2+) influx
      in SFO neurons, which may influence SFO-mediated sympathoexcitation. Our findings
      provide the first evidence of a spatial and functional framework that underlies
      ANG-II signaling in the SFO and reveal novel targets for antihypertensive
      therapies.

PMID- 24014681
TI  - Natural radioactivity in surface soil samples from dwelling areas in Tehran city,
      Iran.
AB  - The study was carried out to determine radioactivity concentrations in surface
      soil samples of the city of Tehran and associated potential radiological hazards.
      The natural radionuclide ((226)Ra, (232)Th and (40)K) contents were determined
      for 50 locations throughout the geological surface formations in a representative
      area in the city of Tehran, Iran, using high-resolution gamma-spectrometric
      analysis. The range of activity concentrations of (226)Ra, (232)Th and (40)K in
      the soil from the studied areas varies from 30.5+/-0.6 to 45.4+/-0.9, 27.3+/-0.5
      to 57.1+/-1.1 and 328.0+/-4.6 to 768.5+/-13.4 Bq kg(-1) with overall mean values
      of 38.8+/-0.7, 43.4+/-0.8 and 555.1+/-8.9 Bq kg(-1), respectively. The mean
      radium equivalent activity, external hazard index, internal hazard index to
      quantify the internal exposure to radon and its daughter products, as well as the
      gamma activity concentration index for each sample are 143.6+/-4.6 Bq kg(-1),
      0.39, 0.49 and 0.53, respectively. The average estimated radium equivalent is
      comparable with reported values for many countries in the world. Therefore, these
      areas may not pose radiological risks to the inhabitants due to harmful effects
      of the ionising radiation from the natural radioactivity in soil. The calculated
      average external and internal hazard indexes were found to be less than unity, as
      a recommended safe level. Estimates of the measured radionuclide content have
      been made for calculating the absorbed dose rate in the outdoor air at 1 m above
      the ground level. The absorbed dose rates resulting from those concentrations
      ranged from 48.1 to 88.7 nGy h(-1). Assuming a 20 % occupancy factor proposed by
      UNSCEAR, 2000, the corresponding effective dose rates in outdoor air equivalent
      to the population were calculated to be between 0.06 and 0.11 mSv y(-1). The
      measurement results and calculated values obtained from this study indicate that
      the dwelling areas in Tehran city, Iran, have background radioactivity levels
      within natural limits. 

PMID- 24014680
TI  - Kir6.2 limits Ca(2+) overload and mitochondrial oscillations of ventricular
      myocytes in response to metabolic stress.
AB  - ATP-sensitive K(+) (KATP) channels are abundant membrane proteins in cardiac
      myocytes that are directly gated by intracellular ATP and form a signaling
      complex with metabolic enzymes, such as creatine kinase. KATP channels are known
      to be essential for adaption to cardiac stress, such as ischemia; however, how
      all the molecular components of the stress response interact is not fully
      understood. We examined the effects of decreasing the KATP current density on
      Ca(2+) and mitochondrial homeostasis and ischemic preconditioning. Acute
      knockdown of the pore-forming subunit, Kir6.2, was achieved using adenoviral
      delivery of short hairpin RNA targeted to Kir6.2. The acute nature of the
      knockdown of Kir6.2 accurately shows the effects of Kir6.2 depletion without any
      compensatory effects that may arise in transgenic studies. We also investigated
      the effect of reducing the KATP current while maintaining KATP channel protein in
      the sarcolemmal membrane using a nonconducting Kir6.2 construct. Only 50% KATP
      current remained after Kir6.2 knockdown, yet there were profound effects on
      myocyte responses to metabolic stress. Kir6.2 was essential for cardiac myocyte
      Ca(2+) homeostasis under both baseline conditions before any metabolic stress and
      after metabolic stress. Expression of nonconducting Kir6.2 also resulted in
      increased Ca(2+) overload, showing the importance of K(+) conductance in the
      protective response. Both ischemic preconditioning and protection during ischemia
      were lost when Kir6.2 was knocked down. KATP current density was also important
      for the mitochondrial membrane potential at rest and prevented mitochondrial
      membrane potential oscillations during oxidative stress. KATP channel density is
      important for adaption to metabolic stress.

PMID- 24014679
TI  - Xanthine oxidase inhibition preserves left ventricular systolic but not diastolic
      function in cardiac volume overload.
AB  - Xanthine oxidase (XO) is increased in human and rat left ventricular (LV)
      myocytes with volume overload (VO) of mitral regurgitation and aortocaval fistula
      (ACF). In the setting of increased ATP demand, XO-mediated ROS can decrease
      mitochondrial respiration and contractile function. Thus, we tested the
      hypothesis that XO inhibition improves cardiomyocyte bioenergetics and LV
      function in chronic ACF in the rat. Sprague-Dawley rats were randomized to either
      sham or ACF +/- allopurinol (100 mg.kg(-1).day(-1), n >=7 rats/group).
      Echocardiography at 8 wk demonstrated a similar 37% increase in LV end-diastolic
      dimension (P < 0.001), a twofold increase in LV end-diastolic pressure/wall
      stress (P < 0.05), and a twofold increase in lung weight (P < 0.05) in treated
      and untreated ACF groups versus the sham group. LV ejection fraction, velocity of
      circumferential shortening, maximal systolic elastance, and contractile
      efficiency were significantly depressed in ACF and significantly improved in ACF
      + allopurinol rats, all of which occurred in the absence of changes in the
      maximum O2 consumption rate measured in isolated cardiomyocytes using the
      extracellular flux analyzer. However, the improvement in contractile function is
      not paralleled by any attenuation in LV dilatation, LV end-diastolic
      pressure/wall stress, and lung weight. In conclusion, allopurinol improves LV
      contractile function and efficiency possibly by diminishing the known XO-mediated
      ROS effects on myofilament Ca(2+) sensitivity. However, LV remodeling and
      diastolic properties are not improved, which may explain the failure of XO
      inhibition to improve symptoms and hospitalizations in patients with severe heart
      failure.

PMID- 24014682
TI  - Magnetic resonance imaging tracking of ferumoxytol-labeled human neural stem
      cells: studies leading to clinical use.
AB  - Numerous stem cell-based therapies are currently under clinical investigation,
      including the use of neural stem cells (NSCs) as delivery vehicles to target
      therapeutic agents to invasive brain tumors. The ability to monitor the time
      course, migration, and distribution of stem cells following transplantation into
      patients would provide critical information for optimizing treatment regimens. No
      effective cell-tracking methodology has yet garnered clinical acceptance. A
      highly promising noninvasive method for monitoring NSCs and potentially other
      cell types in vivo involves preloading them with ultrasmall superparamagnetic
      iron oxide nanoparticles (USPIOs) to enable cell tracking using magnetic
      resonance imaging (MRI). We report here the preclinical studies that led to U.S.
      Food and Drug Administration approval for first-in-human investigational use of
      ferumoxytol to label NSCs prior to transplantation into brain tumor patients,
      followed by surveillance serial MRI. A combination of heparin, protamine sulfate,
      and ferumoxytol (HPF) was used to label the NSCs. HPF labeling did not affect
      cell viability, growth kinetics, or tumor tropism in vitro, and it enabled MRI
      visualization of NSC distribution within orthotopic glioma xenografts. MRI
      revealed dynamic in vivo NSC distribution at multiple time points following
      intracerebral or intravenous injection into glioma-bearing mice that correlated
      with histological analysis. Preclinical safety/toxicity studies of
      intracerebrally administered HPF-labeled NSCs in mice were also performed, and
      they showed no significant clinical or behavioral changes, no neuronal or
      systemic toxicities, and no abnormal accumulation of iron in the liver or spleen.
      These studies support the clinical use of ferumoxytol labeling of cells for post
      transplant MRI visualization and tracking. 

PMID- 24014684
TI  - Regulation of ion transport by oxidants.
AB  - Ion channels perform a variety of cellular functions in lung epithelia. Oxidant-
      and antioxidant-mediated mechanisms (that is, redox regulation) of ion channels
      are areas of intense research. Significant progress has been made in our
      understanding of redox regulation of ion channels since the last Experimental
      Biology report in 2003. Advancements include: 1) identification of nonphagocytic
      NADPH oxidases as sources of regulated reactive species (RS) production in
      epithelia, 2) an understanding that excessive treatment with antioxidants can
      result in greater oxidative stress, and 3) characterization of novel RS signaling
      pathways that converge upon ion channel regulation. These advancements, as
      discussed at the 2013 Experimental Biology Meeting in Boston, MA, impact our
      understanding of oxidative stress in the lung, and, in particular, illustrate
      that the redox state has profound effects on ion channel and cellular function. 

PMID- 24014683
TI  - Activation of developmental nuclear fibroblast growth factor receptor 1 signaling
      and neurogenesis in adult brain by alpha7 nicotinic receptor agonist.
AB  - Reactivation of endogenous neurogenesis in the adult brain or spinal cord holds
      the key for treatment of central nervous system injuries and neurodegenerative
      disorders, which are major health care issues for the world's aging population.
      We have previously shown that activation of developmental integrative nuclear
      fibroblast growth factor receptor 1 (FGFR1) signaling (INFS), via gene
      transfection, reactivates neurogenesis in the adult brain by promoting neuronal
      differentiation of brain neural stem/progenitor cells (NS/PCs). In the present
      study, we report that targeting the alpha7 nicotinic acetylcholine receptors
      (alpha7nAChRs) with a specific TC-7020 agonist led to a robust accumulation of
      endogenous FGFR1 in the cell nucleus. Nuclear FGFR1 accumulation was accompanied
      by an inhibition of proliferation of NS/PCs in the subventricular zone (SVZ) and
      by the generation of new neurons. Neuronal differentiation was observed in
      different regions of the adult mouse brain, including (a) betaIII-Tubulin
      expressing cortical neurons, (b) calretinin-expressing hippocampal neurons, and
      (c) cells in substantia nigra expressing the predopaminergic Nurr1+ phenotype.
      Furthermore, we showed that in vitro stimulation of neural stem/progenitor cells
      with alpha7nAChR agonist directly activated INFS and neuronal-like
      differentiation. TC-7020 stimulation of the betaIII-Tubulin gene was accompanied
      by increased binding of FGFR1, CREB binding protein, and RNA polymerase II to a
      Nur77 targeted promoter region. TC-7020 augmented Nur77-dependent activation of
      nerve growth factor inducible-B protein responsive element, indicating that
      alpha7nAChR upregulation of betaIII-Tubulin involves neurogenic FGFR1-Nur
      signaling. The reactivation of INFS and neurogenesis in adult brain by the
      alpha7nAChR agonist may offer a new strategy to treat brain injuries,
      neurodegenerative diseases, and neurodevelopmental diseases. 

PMID- 24014685
TI  - Mesenchymal stromal cell turnover in the normal adult lung revisited.
AB  - We have employed a simple and robust noninvasive method of continuous in vivo
      long-term bromodeoxyuridine (BrdU) labeling to analyze lung mesenchymal stromal
      cell turnover in adult mice in the steady state. Mathematical modeling of BrdU
      uptake in flow cytometrically sorted CD45(neg)CD31(neg)Sca-1(pos) lung cells
      following long-term feeding of BrdU to mice in their drinking water reveals that
      lung mesenchymal stromal cells cycle continuously throughout life. Analysis of
      BrdU incorporation during long-term feeding and during chasing (delabeling)
      following replacement of BrdU-water with normal water shows that the
      CD45(neg)CD31(neg)Sca-1(pos) lung mesenchymal stromal cell compartment turns over
      at a rate of ~2.26% per day with a time to half-cycled of 44 days, an estimated
      cell proliferation rate of 0.004/day, and a cell death rate of 0.018/day. 

PMID- 24014686
TI  - Protein expression profile of rat type two alveolar epithelial cells during
      hyperoxic stress and recovery.
AB  - In rodent model systems, the sequential changes in lung morphology resulting from
      hyperoxic injury are well characterized and are similar to changes in human acute
      respiratory distress syndrome. In the injured lung, alveolar type two (AT2)
      epithelial cells play a critical role in restoring the normal alveolar structure.
      Thus characterizing the changes in AT2 cells will provide insights into the
      mechanisms underpinning the recovery from lung injury. We applied an unbiased
      systems-level proteomics approach to elucidate molecular mechanisms contributing
      to lung repair in a rat hyperoxic lung injury model. AT2 cells were isolated from
      rat lungs at predetermined intervals during hyperoxic injury and recovery.
      Protein expression profiles were determined by using iTRAQ with tandem mass
      spectrometry. Of the 959 distinct proteins identified, 183 significantly changed
      in abundance during the injury-recovery cycle. Gene ontology enrichment analysis
      identified cell cycle, cell differentiation, cell metabolism, ion homeostasis,
      programmed cell death, ubiquitination, and cell migration to be significantly
      enriched by these proteins. Gene set enrichment analysis of data acquired during
      lung repair revealed differential expression of gene sets that control
      multicellular organismal development, systems development, organ development, and
      chemical homeostasis. More detailed analysis identified activity in two
      regulatory pathways, JNK and miR 374. A novel short time-series expression miner
      algorithm identified protein clusters with coherent changes during injury and
      repair. We concluded that coherent changes occur in the AT2 cell proteome in
      response to hyperoxic stress. These findings offer guidance regarding the
      specific molecular mechanisms governing repair of the injured lung. 

PMID- 24014688
TI  - Fourteen problems: but not Mid-Staffordshire.

PMID- 24014689
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 1: Brachial arterial blood sampling: safe or not?
AB  - A shortcut review was carried out to establish whether brachial artery puncture
      is safe in patients requiring arterial blood sampling. 47 papers were found using
      the reported searches, of which one presented the best evidence to answer the
      clinical question. The author, date and country of publication, patient group
      studied, study type, relevant outcomes, results and study weaknesses of this
      paper are tabulated. It is concluded that brachial artery puncture is likely to
      be safe in the non-shocked patient who is not on concurrent anticoagulant
      therapy. 

PMID- 24014687
TI  - Comparison of computer tomographic volumetry versus nuclear split renal function
      to determine residual renal function after living kidney donation.
AB  - BACKGROUND: Living-donor kidney transplantation is an established practice.
      Traditionally a combination of renal scintigram and computed tomography (CT) is
      used to select the kidney that is to be harvested in each donor. PURPOSE: To
      evaluate the ability of split renal volume (SRV) calculated from volumetric
      examination of CT images compared to nuclear split renal function (nSRF) derived
      from gamma camera scintigram to predict donor residual single kidney function
      after donor nephrectomy. MATERIAL AND METHODS: This pilot study comprised a
      retrospective analysis of CT images and renal scintigrams from 12 subsequent live
      kidney donors who had at least 12 months post-donation renal function follow-up.
      RESULTS: nSRF derived from the renal scintigram, expressed as the right kidney's
      function in percent of the total, was 50.2 +/- 3.3 (range, 44.1-54.0%) and SRV
      estimated following analysis of CT imaging was 49.0 +/- 2.9 (range, 46.4-52.3%).
      Although the correlation between nSRF and SRV was moderate (R = 0.46), there was
      92% agreement on the dominant kidney if a difference of <2% in nSRF versus SRV
      was considered. Post-donation glomerular filtration rate (GFR) by CKD-EPI formula
      was 92 +/- 10 mL/min/1.73m2 at 1 year and the correlation between estimated GFR
      (eGFR) at 1 year and extrapolated single kidney eGFR adjusted by nSRF (R(2 )=
      0.69, P = 0.0007) or SRV (R(2 )= 0.74, P = 0.0003) was similar. CONCLUSION:
      Calculation of SRV from pre-donation CT examination is a valid method to estimate
      nSRF with good concordance with nSRF determined by renal scintigram and could
      replace the latter in the assessment of potential kidney donors.

PMID- 24014691
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 2: Is shift work bad for you?
AB  - A shortcut review was carried out to establish whether night shift working
      worsens health and shortens life. 127 papers were found using the reported
      searches, of which one systematic review presented the best evidence to answer
      the clinical question. The author, date and country of publication, patient group
      studied, study type, relevant outcomes, results and study weaknesses of this
      paper are tabulated. It is concluded that shift work is associated with an
      increased risk of vascular events but does not appear to have an effect on
      mortality. 

PMID- 24014692
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. BET 3: Is nebulised naloxone effective in opioid overdose?
AB  - A shortcut review was carried out to establish whether nebulised naloxone is a
      safe and effective alternative to intravenous naloxone in patients with suspected
      opioid overdose. 18 papers were found using the reported searches, of which two
      presented the best evidence to answer the clinical question. The author, date and
      country of publication, patient group studied, study type, relevant outcomes,
      results and study weaknesses of these papers are tabulated. It is concluded that
      nebulised naloxone is a safe and effective firstline alternative to parenteral
      naloxone in spontaneously breathing patients with suspected opioid overdose. 

PMID- 24014693
TI  - Short answer question case series: noisy breathing in an adult.

PMID- 24014731
TI  - Arterial stiffness parameters should be evaluated with different types of
      psoriasis.

PMID- 24014732
TI  - Assessment of liver fibrosis by transient elastography in patients with HIV and
      hepatitis B virus coinfection in Nigeria.

PMID- 24014733
TI  - Preventing Campylobacter at the source: why is it so difficult?
AB  - Campylobacteriosis in humans, caused by Campylobacter jejuni and Campylobacter
      coli, is the most common recognized bacterial zoonosis in the European Union and
      the United States. The acute phase is characterized by gastrointestinal symptoms.
      The long-term sequelae (Guillain-Barre syndrome, reactive arthritis, and
      postinfectious irritable bowel syndrome) contribute considerably to the disease
      burden. Attribution studies identified poultry as the reservoir responsible for
      up to 80% of the human Campylobacter infections. In the European Union, an
      estimated 30% of the human infections are associated with consumption and
      preparation of poultry meat. Until now, interventions in the poultry meat
      production chain have not been effectively introduced except for targeted
      interventions in Iceland and New Zealand. Intervention measures (eg, biosecurity)
      have limited effect or are hampered by economic aspects or consumer acceptance.
      In the future, a multilevel approach should be followed, aiming at reducing the
      level of contamination of consumer products rather than complete absence of
      Campylobacter. 

PMID- 24014734
TI  - Vitamin D3 supplementation and upper respiratory tract infections in a
      randomized, controlled trial.
AB  - BACKGROUND: Randomized controlled trials testing the association between vitamin
      D status and upper respiratory tract infection (URTI) have given mixed results.
      During a multicenter, randomized controlled trial of colorectal adenoma
      chemoprevention, we tested whether 1000 IU/day vitamin D(3) supplementation
      reduced winter episodes and duration of URTI and its composite syndromes,
      influenza-like illness (ILI; fever and >=2 of sore throat, cough, muscle ache, or
      headache) and colds (no fever, and >=2 of runny nose, nasal congestion, sneezing,
      sore throat, cough, swollen or tender neck glands). METHODS: The 2259 trial
      participants were aged 45-75, in good health, had a history of colorectal
      adenoma, and had a serum 25-hydroxyvitamin D level >=12 ng/mL. They were
      randomized to vitamin D(3) (1000 IU/day), calcium (1200 mg/day), both, or
      placebo. Of these, 759 participants completed daily symptom diaries. Secondary
      data included semiannual surveys of all participants. RESULTS: Among those who
      completed symptom diaries, supplementation did not significantly reduce winter
      episodes of URTI (rate ratio [RR], 0.93; 95% confidence interval [CI], .79-1.09)
      including colds (RR, 0.93; 95% CI, .78-1.10) or ILI (RR, 0.95; 95% CI, .62-1.46),
      nor did it reduce winter days of illness (RR, 1.13; 95% CI, .90-1.43). There was
      no significant benefit according to adherence, influenza vaccination, body mass
      index, or baseline vitamin D status. Semiannual surveys of all participants (N =
      2228) identified no benefit of supplementation on ILI (odds ratio [OR], 1.14; 95%
      CI, .84-1.54) or colds (OR, 1.03; 95% CI, .87-1.23). CONCLUSIONS: Supplementation
      with 1000 IU/day vitamin D(3) did not significantly reduce the incidence or
      duration of URTI in adults with a baseline serum 25-hydroxyvitamin D level >=12
      ng/mL.

PMID- 24014736
TI  - Fluzone high-dose vaccine is significantly more effective than the standard dose
      of fluzone vaccine in preventing influenza in adults >=65 years of age.

PMID- 24014735
TI  - Economics of malaria prevention in US travelers to West Africa.
AB  - BACKGROUND: Pretravel health consultations help international travelers manage
      travel-related illness risks through education, vaccination, and medication. This
      study evaluated costs and benefits of that portion of the health consultation
      associated with malaria prevention provided to US travelers bound for West
      Africa. METHODS: The estimated change in disease risk and associated costs and
      benefits resulting from traveler adherence to malaria chemoprophylaxis were
      calculated from 2 perspectives: the healthcare payer's and the traveler's. We
      used data from the Global TravEpiNet network of US travel clinics that collect de
      identified pretravel data for international travelers. Disease risk and
      chemoprophylaxis effectiveness were estimated from published medical reports.
      Direct medical costs were obtained from the Nationwide Inpatient Sample and
      published literature. RESULTS: We analyzed 1029 records from January 2009 to
      January 2011. Assuming full adherence to chemoprophylaxis regimens, consultations
      saved healthcare payers a per-traveler average of $14 (9-day trip) to $372 (30
      day trip). For travelers, consultations resulted in a range of net cost of $20 (9
      day trip) to a net savings of $32 (30-day trip). Differences were mostly driven
      by risk of malaria in the destination country. CONCLUSIONS: Our model suggests
      that healthcare payers save money for short- and longer-term trips, and that
      travelers save money for longer trips when travelers adhere to malaria
      recommendations and prophylactic regimens in West Africa. This is a potential
      incentive to healthcare payers to offer consistent pretravel preventive care to
      travelers. This financial benefit complements the medical benefit of reducing the
      risk of malaria.

PMID- 24014737
TI  - The significance of previous invasive and orthodontic treatment experiences on
      children's dental fear.
AB  - OBJECTIVES: The aim was to find out if children who have gone through orthodontic
      and invasive treatment have less dental fear than children who have experienced
      only invasive treatment or no treatment at all. MATERIALS AND METHODS: The data
      consisted of 910 9- to 15-year-old children from Jyvaskyla and Kuopio, Finland. A
      questionnaire was used that contained 11 dental fear-related questions and family
      member's dental fear and questions on oral health habits and family
      characteristics. Information on treatment procedures from three preceding years
      was collected from patient records. To study the association between dental fear
      and treatment experiences, analysis of variance, and multiple logistic regression
      analyses were performed. RESULTS: Dental fear was found more often in children
      who had experiences of orthodontic treatment experiences and invasive treatment
      than in children with invasive treatment only or no treatment experiences at all.
      LIMITATIONS: Different orthodontic treatment experiences were not analysed
      individually, and the study was retrospective. CONCLUSION: Familiarization to
      dental treatment via orthodontic procedures does not necessarily decrease dental
      fear among children.

PMID- 24014738
TI  - Bilateral hypodontia is more common than unilateral hypodontia in children with
      Down syndrome: a prospective population-based study.
AB  - BACKGROUND: In individuals with simple hypodontia, congenital absence of teeth
      commonly affects just one tooth of a pair, not both. However, patterns of
      hypodontia have not been fully explored in children with Down syndrome (DS).
      OBJECTIVE: We describe the frequency and left-right symmetry of hypodontia in the
      permanent dentition of 8- to 9-year-old Norwegian children with DS. MATERIALS AND
      METHODS: This population-based cross-sectional study was part of a national
      prospective study evaluating upper airway function, hearing, dental, and
      craniofacial characteristics in a cohort of children with DS born in 2002. The
      cohort consisted of 29 children with DS and represented 57 per cent of all
      children born with DS in Norway in 2002. Hypodontia was assessed using panoramic
      and/or dental radiographs. Data were collected prospectively at TAKO-Centre,
      National Resource Centre for Oral Health in Rare Medical Conditions, Lovisenberg
      Diakonale Hospital, Oslo, Norway. RESULTS: Hypodontia of permanent teeth,
      excluding third molars, was found in 61.5 per cent of the 26 children included in
      the final sample. Among the 16 children with hypodontia, 75.0 per cent were
      missing two or more permanent teeth. Two children (7.7 per cent) had severe
      hypodontia (oligodontia). The teeth most often missing were the maxillary lateral
      incisors, followed by the mandibular second premolars and maxillary second
      premolars. Most (68.9 per cent) cases of hypodontia occurred bilaterally.
      CONCLUSIONS: The majority of the children with DS were missing one or more
      permanent teeth. Unlike in the general population, bilateral hypodontia was more
      common than unilateral hypodontia in this sample of children with DS.

PMID- 24014740
TI  - Standards launched to help regulate pet advertising online.

PMID- 24014739
TI  - Concurrent overexpression of RET/PTC1 and TTF1 confers tumorigenicity to
      thyrocytes.
AB  - A variant located on 14q13.3 nearest to thyroid transcription factor-1 (TTF1)
      predisposes individuals to thyroid cancer, but whether this variant is related to
      the RET/PTC rearrangement associated with human papillary thyroid carcinomas
      (PTCs) is unknown. The aims of this study were to investigate the effects of
      RET/PTC1 on the expression of thyroid-specific genes in thyrocytes and their
      relationship with malignant transformation of the thyrocytes. In the absence or
      presence of TSH, an extracellular signal-regulated kinase was phosphorylated in
      FRTL5 cells that stably expressed RET/PTC1, and these cells grew independently of
      TSH. FRTL (RET/PTC1) cells produced 566% more thyroglobulin mRNA and 474% more
      Na+/I- symporter mRNA than did the control FRTL (pcDNA) cells. FRTL (RET/PTC1)
      cells expressed 468% more Ttf1 mRNA than did FRTL (pcDNA) cells, but these two
      cell types did not differ significantly with respect to Pax8 or Ttf2 mRNA levels.
      When FRTL (RET/PTC1) cells and FRTL (pcDNA), cells were injected into each of
      nine nude mice, each mouse developed a single tumor at the site of FRTL
      (RET/PTC1) cell injection; in contrast, tumor formation never occurred at sites
      of FRTL (cDNA) cells injection. Tumors resulting from FRTL (RET/PTC1) cells
      retained (125)I-uptake activity; moreover, the cells invaded into surrounding
      skeletal muscle. When overexpression of Ttf1 in FRTL (RET/PTC1) cells was
      silenced, the cells completely lost their tumorigenic potential. Exogenous TTF1
      cDNA enhanced the tumorigenicity of BHP18-21v cells, human PTC cells that express
      RET/PTC1, in nude mice. These results indicated that concurrent overexpression of
      RET/PTC1 and TTF1 confers tumorigenicity to FRTL5 and BHP18-21v cells in nude
      mice.

PMID- 24014741
TI  - Call for more safeguards for wild animals in captivity.

PMID- 24014742
TI  - Vet jailed for insurance fraud.

PMID- 24014743
TI  - Summer school gives an insight into the role of vets in agriculture.

PMID- 24014746
TI  - PDSA presents posthumous gold medal to New Zealand police dog.

PMID- 24014745
TI  - Vets urged to be partners in sustainable development.

PMID- 24014748
TI  - Obesity is a complex issue.

PMID- 24014750
TI  - Confirmation of SBV disease in Aberdeenshire.

PMID- 24014751
TI  - Testing mammary gland secretions to help predict when a mare will foal.

PMID- 24014752
TI  - Mass mortality of puffins, linked to starvation.

PMID- 24014753
TI  - RCVS fellowship proposals.

PMID- 24014754
TI  - Veterinary clinical trials in the UK.

PMID- 24014755
TI  - Veterinary clinical trials in the UK.

PMID- 24014756
TI  - Collaborating on One Health.

PMID- 24014764
TI  - Mutations on the N-terminal edge of the DELSEED loop in either the alpha or beta
      subunit of the mitochondrial F1-ATPase enhance ATP hydrolysis in the absence of
      the central gamma rotor.
AB  - F(1)-ATPase is a rotary molecular machine with a subunit stoichiometry of
      alpha(3)beta(3)gamma(1)delta(1)epsilon(1). It has a robust ATP-hydrolyzing
      activity due to effective cooperativity between the three catalytic sites. It is
      believed that the central gamma rotor dictates the sequential conformational
      changes to the catalytic sites in the alpha(3)beta(3) core to achieve
      cooperativity. However, recent studies of the thermophilic Bacillus PS3 F(1)
      ATPase have suggested that the alpha(3)beta(3) core can intrinsically undergo
      unidirectional cooperative catalysis (T. Uchihashi et al., Science 333:755-758,
      2011). The mechanism of this gamma-independent ATP-hydrolyzing mode is unclear.
      Here, a unique genetic screen allowed us to identify specific mutations in the
      alpha and beta subunits that stimulate ATP hydrolysis by the mitochondrial F(1)
      ATPase in the absence of gamma. We found that the F446I mutation in the alpha
      subunit and G419D mutation in the beta subunit suppress cell death by the loss of
      mitochondrial DNA (rho(o)) in a Kluyveromyces lactis mutant lacking gamma. In
      organello ATPase assays showed that the mutant but not the wild-type gamma-less
      F(1) complexes retained 21.7 to 44.6% of the native F(1)-ATPase activity. The
      gamma-less F(1) subcomplex was assembled but was structurally and functionally
      labile in vitro. Phe446 in the alpha subunit and Gly419 in the beta subunit are
      located on the N-terminal edge of the DELSEED loops in both subunits. Mutations
      in these two sites likely enhance the transmission of catalytically required
      conformational changes to an adjacent alpha or beta subunit, thereby allowing
      robust ATP hydrolysis and cell survival under rho(o) conditions. This work may
      help our understanding of the structural elements required for ATP hydrolysis by
      the alpha(3)beta(3) subcomplex.

PMID- 24014765
TI  - Restricted substrate specificity for the geranylgeranyltransferase-I enzyme in
      Cryptococcus neoformans: implications for virulence.
AB  - Proper cellular localization is required for the function of many proteins. The
      CaaX prenyltransferases (where CaaX indicates a cysteine followed by two
      aliphatic amino acids and a variable amino acid) direct the subcellular
      localization of a large group of proteins by catalyzing the attachment of
      hydrophobic isoprenoid moieties onto C-terminal CaaX motifs, thus facilitating
      membrane association. This group of enzymes includes farnesyltransferase (Ftase)
      and geranylgeranyltransferase-I (Ggtase-1). Classically, the variable (X) amino
      acid determines whether a protein will be an Ftase or Ggtase-I substrate, with
      Ggtase-I substrates often containing CaaL motifs. In this study, we identify the
      gene encoding the beta subunit of Ggtase-I (CDC43) and demonstrate that Ggtase
      mediated activity is not essential. However, Cryptococcus neoformans CDC43 is
      important for thermotolerance, morphogenesis, and virulence. We find that Ggtase
      I function is required for full membrane localization of Rho10 and the two Cdc42
      paralogs (Cdc42 and Cdc420). Interestingly, the related Rac and Ras proteins are
      not mislocalized in the cdc43Delta mutant even though they contain similar CaaL
      motifs. Additionally, the membrane localization of each of these GTPases is
      dependent on the prenylation of the CaaX cysteine. These results indicate that C.
      neoformans CaaX prenyltransferases may recognize their substrates in a unique
      manner from existing models of prenyltransferase specificity. It also suggests
      that the C. neoformans Ftase, which has been shown to be more important for C.
      neoformans proliferation and viability, may be the primary prenyltransferase for
      proteins that are typically geranylgeranylated in other species. 

PMID- 24014768
TI  - Editorial: Evidence-based medicine.

PMID- 24014766
TI  - Structural and functional characterization of the N terminus of
      Schizosaccharomyces pombe Cwf10.
AB  - The spliceosome is a dynamic macromolecular machine that catalyzes the removal of
      introns from pre-mRNA, yielding mature message. Schizosaccharomyces pombe Cwf10
      (homolog of Saccharomyces cerevisiae Snu114 and human U5-116K), an integral
      member of the U5 snRNP, is a GTPase that has multiple roles within the splicing
      cycle. Cwf10/Snu114 family members are highly homologous to eukaryotic
      translation elongation factor EF2, and they contain a conserved N-terminal
      extension (NTE) to the EF2-like portion, predicted to be an intrinsically
      unfolded domain. Using S. pombe as a model system, we show that the NTE is not
      essential, but cells lacking this domain are defective in pre-mRNA splicing.
      Genetic interactions between cwf10-DeltaNTE and other pre-mRNA splicing mutants
      are consistent with a role for the NTE in spliceosome activation and second-step
      catalysis. Characterization of Cwf10-NTE by various biophysical techniques shows
      that in solution the NTE contains regions of both structure and disorder. The
      first 23 highly conserved amino acids of the NTE are essential for its role in
      splicing but when overexpressed are not sufficient to restore pre-mRNA splicing
      to wild-type levels in cwf10-DeltaNTE cells. When the entire NTE is overexpressed
      in the cwf10-DeltaNTE background, it can complement the truncated Cwf10 protein
      in trans, and it immunoprecipitates a complex similar in composition to the late
      stage U5.U2/U6 spliceosome. These data show that the structurally flexible NTE is
      capable of independently incorporating into the spliceosome and improving
      splicing function, possibly indicating a role for the NTE in stabilizing
      conformational rearrangements during a splice cycle. 

PMID- 24014767
TI  - Clonal variants of Plasmodium falciparum exhibit a narrow range of rolling
      velocities to host receptor CD36 under dynamic flow conditions.
AB  - Cytoadhesion of Plasmodium falciparum parasitized red blood cells (pRBCs) has
      been implicated in the virulence of malaria infection. Cytoadhesive interactions
      are mediated by the protein family of Plasmodium falciparum erythrocyte membrane
      protein 1 (PfEMP1). The PfEMP1 family is under strong antibody and binding
      selection, resulting in extensive sequence and size variation of the
      extracellular domains. Here, we investigated cytoadhesion of pRBCs to CD36, a
      common receptor of P. falciparum field isolates, under dynamic flow conditions.
      Isogeneic parasites, predominantly expressing single PfEMP1 variants, were
      evaluated for binding to recombinant CD36 under dynamic flow conditions using
      microfluidic devices. We tested if PfEMP1 size (number of extracellular domains)
      or sequence variation affected the pRBC-CD36 interaction. Our analysis showed
      that clonal parasite variants varied ~5-fold in CD36 rolling velocity despite
      extensive PfEMP1 sequence polymorphism. In addition, adherent pRBCs exhibited a
      characteristic hysteresis in rolling velocity at microvascular flow rates, which
      was accompanied by changes in pRBC shape and may represent important adaptations
      that favor stable binding. 

PMID- 24014769
TI  - Commentary: Antibiotic-coated pins for prevention of pin-tract infection: a
      rabbit study.

PMID- 24014770
TI  - Commentary: Correlation between trochlear dysplasia and anterior cruciate
      ligament injury.

PMID- 24014771
TI  - Comparison of different warfarin reversal protocols on surgical delay and
      complication rate in hip fracture patients.
AB  - PURPOSE. To compare the effects of different warfarin reversal protocols on
      surgical delay and complication rate in hip fracture patients. METHODS. Records
      of 7 men and 17 women aged 68 to 93 (mean, 82) years who were on warfarin and
      underwent surgery for femoral neck fractures were reviewed. The time to surgery,
      complication rate, and mortality were recorded, as were the International
      Normalised Ratio (INR) on admission and the day of operation, as well as the
      dose, route, and time of administration of vitamin K for reversing the
      anticoagulation effect of warfarin. Patients were divided into 4 groups based on
      the warfarin reversal treatment. Group 1 (n=4) included patients who did not
      receive reversal treatment, as their admission INR was 1.5 or less. Group 2 (n=6)
      included patients who did not receive reversal treatment even though their INR
      was >1.6. Group 3 (n=5) included patients who received inappropriate reversal
      treatment (late or low-dose oral administration). Group 4 (n=9) included patients
      who received appropriate reversal treatment in terms of dose, route, and time of
      administration. RESULTS. Among the 4 groups, the mean INR was 2.2 (range, 1.3
      4.6) on admission and 1.4 (range, 1.0-1.6) on the day of surgery. Group 1 was
      excluded from further analysis. Respectively in groups 2, 3, and 4, the mean
      times to surgery were 2.3, 2.6, and 1.2 days, and the complication rates were
      67%, 20%, and 11%. CONCLUSION. Early administration of intravenous vitamin K for
      hip fracture patients on warfarin is recommended to ensure early operative
      management and avoid postoperative complications. 

PMID- 24014773
TI  - Surgical outcome for hip fractures in patients with and without Parkinson's
      disease.
AB  - PURPOSE. To compare surgical outcome of hip fractures (in terms of the ability to
      walk and complications) in patients with and without Parkinson's disease (PD).
      METHODS. Records of 207 patients who underwent surgery for femoral neck fractures
      were reviewed. Of whom, 9 men and 26 women with PD aged 58 to 89 (mean, 76.8)
      years underwent hemiarthroplasty for subcapital fractures (n=22) or internal
      fixation for intertrochanteric fractures (n=13). The remaining 36 men and 136
      women with no PD aged 61 to 96 (mean, 81.8) years underwent hemiarthroplasty
      (n=108) or internal fixation (n=64) for subcapital (n=120) or intertrochanteric
      (n=52) fractures. None of the patients had pathological fractures, and all had
      been ambulatory prior to the fracture. According to the Columbia classification
      system, severity of PD was grade II in 11, grade III in 11, and grade IV in 13
      patients. RESULTS. Respectively for the patients with and without PD at the one
      year follow-up, 68.2% and 79.6% of those treated with hemiarthroplasty and 46.2%
      and 62.5% of those treated with internal fixation were able to walk with or
      without assistive devices. 81.8%, 63.6%, and 38.5% of the patients with grade-II,
      -III, and -IV PD, respectively, were able to walk at the one-year follow-up,
      compared to 73.3% of the patients without PD. CONCLUSION. Surgical treatment for
      hip fractures was appropriate for patients with grade-II or -III PD. 

PMID- 24014772
TI  - Withholding clopidogrel for 3 to 6 versus 7 days or more before surgery in hip
      fracture patients.
AB  - PURPOSE. To compare morbidity and mortality after hip fracture surgery in
      patients withholding clopidogrel for 3 to 6 days versus >=7 days or more.
      METHODS. Records of 16 men and 31 women aged 49 to 92 (mean, 80.2) years who
      underwent hip fracture surgery after withholding clopidogrel for 3 to 6 days
      (n=24) versus >=7 days or more (n=23) were compared. The patients were taking
      clopidogrel owing to ischaemic heart disease (n=37), cerebrovascular disease
      (n=7), and intolerance to aspirin (n=3). Patient demographics, American Society
      of Anesthesiologists status, preoperative delay, length of hospital stay,
      perioperative haemoglobin reduction, receipt of blood and platelet transfusions,
      morbidity, and mortality were recorded. RESULTS. Respectively in the early
      surgery and delayed-surgery groups, the mean surgical delay was 4.2 and 8.0 days,
      the mean length of hospital stay was 21.1 and 28.7 days, the mean peri-operative
      haemoglobin reduction was 1.5 and 1.1 g/dl, the mean units of blood transfusion
      per patient was 0.8 and 0.7. No severe intra-operative bleeding or wound
      haematoma was encountered in either group. Two patients in each group died within
      one month, and 2 more in the delayed-surgery group died within 3 months. The main
      cause of death was cardiovascular. CONCLUSION. Withholding clopidogrel for <7
      days before surgery conferred no increased risk in hip fracture patients.

PMID- 24014774
TI  - Complications and their risk factors following hip fracture surgery.
AB  - PURPOSE. To evaluate various postoperative complications and their risk factors
      in hip fracture patients. METHODS. 207 female and 87 male consecutive patients
      (mean age, 78.1 years) who underwent surgical (n=242) or conservative (n=52)
      treatment for closed fractures of the femoral neck (n=157) or peritrochanter
      (n=137) were prospectively studied. The types of complication and outcome were
      recorded. The comorbidity status of the patients was categorised based on the
      American Society of Anesthesiologists (ASA) classification. Complications and
      their associations with various risk factors and mortality were analysed.
      RESULTS. For all patients, the mean length of hospitalisation was 14.6 days. For
      the 242 patients who underwent surgical treatment after a mean of 3.6 days, 56.8%
      of them had at least one complication. Acute urinary retention (39.3%) and
      urinary tract infection (24.0%) were most common. Patients with ASA grade III or
      higher had 2.3 fold higher risk of developing complications than those with lower
      grade comorbidity, whereas patients with delayed operation (>48 hours after
      presentation) had 1.8 fold higher risk of developing complications than those
      without delayed operation. Four patients died in hospital: 2 from myocardial
      infarction and 2 from upper gastrointestinal bleeding. CONCLUSION. Complications
      after hip fracture surgery were common. Advanced age, high ASA status, and delay
      in surgery were associated with higher complication rates. Operations should be
      performed on medically fit patients as early as possible. 

PMID- 24014775
TI  - Blocking screws: an adjunct to retrograde nailing for distal femoral shaft
      fractures.
AB  - PURPOSE. To review records of 11 patients who underwent retrograde nailing in
      conjunction with blocking screws to aid fracture reduction for distal femoral
      shaft fractures. METHODS. Records of 8 men and 3 women aged 27 to 60 (mean, 41)
      years who underwent retrograde nailing with the use of blocking screws for distal
      femoral shaft fractures were reviewed. Two of the fractures were open and graded
      as Gustilo-Anderson grade II. The mean surgical delay was 2 (range, 1-5) days.
      RESULTS. All fractures united after a mean of 14 (range, 11-16) weeks without
      malalignment. There was no screw breakage, screw bending, or wound infection.
      CONCLUSION. Blocking screws increase the stability of the construct and thereby
      minimise macro-motion at the fracture site. 

PMID- 24014776
TI  - Correlation between the forearm plus little finger length and the femoral length.
AB  - PURPOSE. To assess the correlation between the forearm plus little finger length
      and the femoral length in 100 volunteers. METHODS. The forearm plus little finger
      length and the ipsilateral femoral length of 68 male and 32 female volunteers
      aged 19 to 55 (mean, 35.8) years were measured using a measuring tape. The
      forearm plus litter finger length was measured from the tip of the olecranon to
      the tip of the little finger, whereas the femoral length was measured from the
      tip of the greater trochanter to the level of proximal pole of the patella over
      the outer aspect of thigh. Two observers made the measurements on 2 separate
      occasions. Intra- and inter-observer variations were calculated. A value of 0.75
      or greater indicated excellent agreement. RESULTS. The mean forearm plus little
      finger length and femoral length were 39.87 (SD, 2.73) and 39.85 (SD, 2.44) cm,
      respectively. The mean difference between these 2 measurements was 0.028 (95% CI,
      -0.109 to 0.165) cm. The correlation between these 2 measurements was 0.861
      (p<0.001). Patient age, sex, and body mass index did not affect this correlation.
      The intra- and inter-observer reliability was excellent. CONCLUSION. The forearm
      plus little finger length correlated with the femoral length. This method is
      simple, radiation-free, and can be applied in day-today practice.

PMID- 24014777
TI  - Effect of calcium triphosphate cement on proximal humeral fracture
      osteosynthesis: a finite element analysis.
AB  - PURPOSE. To measure the effect of void-filling calcium triphosphate cement on the
      loads at the implant-bone interface of a proximal humeral fracture osteosynthesis
      using a finite element analysis. METHODS. Finite element models of a 3-part
      proximal humeral fracture fixed with a plate with and without calcium
      triphosphate cement augmentation were generated from a quantitative computed
      tomography dataset of an intact proximal humerus. Material properties were
      assigned to bone fragments using published expressions relating Young's modulus
      to local Hounsfield number. Boundary conditions were then applied to the model to
      replicate the physiological loads. The effect of void-filling calcium
      triphosphate cement was analysed. RESULTS. When the void was filled with calcium
      triphosphate cement, the pressure gradient of the bone surrounding the screws in
      the medial fracture fragment decreased 97% from up to 21.41 to 0.66 MPa. Peak
      pressure of the fracture planes decreased 95% from 6.10 to 0.30 MPa and occurred
      along the medial aspect. The mean stress in the screw locking mechanisms
      decreased 78% from 71.23 to 15.92 MPa. The angled proximal metaphyseal screw had
      the highest stress. CONCLUSION. Augmentation with calcium triphosphate cement
      improves initial stability and reduces stress on the implant-bone interface. 

PMID- 24014778
TI  - Effect of calcium triphosphate cement on proximal humeral fracture
      osteosynthesis: a cadaveric biomechanical study.
AB  - PURPOSE. To evaluate the effect of filling a central humeral bone void with
      calcium triphosphate cement on the strength and stability of an osteosynthesis in
      elderly cadavers. METHODS. 14 fresh cadaveric shoulder specimens obtained from 11
      donors (mean age, 91.5 years; mean body weight, 61 kg) were divided into 2 age-
      and sex-matched groups. A standardised 3-part proximal humeral fracture with a
      central bone void was created in each specimen. Each specimen was reduced and
      fixed with a locking plate. In half the specimens the central bone void was
      packed with calcium triphosphate cement. The intra-fragmentary motion and the
      load and mode of failure were recorded. RESULTS. Respectively in the test group
      and controls, the intra-fragmentary motion was 1.0 and 6.4 mm, and the peak
      displacement at the 500 N load was 1.8 and 9.1 mm. The Cohen's d was 1.6 to 2.7
      for all load steps, indicating a large effect of the calcium triphosphate cement
      on strength and stability. The mean difference in the failure load was 300 N
      (p<0.05). CONCLUSION. Construct stability and failure load improved significantly
      when the central humeral bone void was filled with calcium triphosphate cement. 

PMID- 24014779
TI  - Open reduction and Kirschner wire fixation with triceps lengthening for neglected
      elbow dislocations.
AB  - PURPOSE. To evaluate outcome of open reduction and Kirschner wire fixation with
      triceps lengthening for neglected elbow dislocations. METHODS. Records of 6 women
      and 14 men aged 7 to 60 (mean, 20) years who underwent open reduction and
      Kirschner wire fixation with triceps lengthening for neglected elbow dislocations
      were reviewed. The dislocations were posterolateral (n=11), posterior (n=4), and
      posteromedial (n=5). No patient had a neurologic deficit. Elbow stiffness was the
      main indication for surgery. The duration of dislocation was 25 to 45 days in 11
      patients and >45 days in 9; the mean was 47 days. The Mayo Elbow Performance
      Index (MEPI) was used to assess outcome at the final follow-up. The maximum score
      was 100. Scores of 90 to 100 were considered excellent, 75 to 89 good, 60 to 74
      fair, and <60 poor. RESULTS. The mean follow-up period was 39.1 months. At the
      final follow-up, the mean MEPI score was 79.3; outcome was excellent in 6
      patients, good in 8, fair in 4, and poor in 2. The mean MEPI was 86.4 and 70.6
      for patients with <=45 or less and >45 days of dislocation, respectively. The
      mean range of movement improved from 20 to 84.5 degrees (p<0.001). The 2 groups
      were significantly different in terms of MEPI (p=0.005) and range of movement
      (p=0.001). The MEPI correlated negatively with the duration of dislocation (r= 
      0.562, p=0.01). The range of movement correlated negatively with patient age (r= 
      0.649, p=0.002). CONCLUSION. Open reduction and Kirschner wire fixation with
      triceps lengthening, together with active postoperative elbow movements achieved
      favourable results for neglected elbow dislocations, especially in younger
      patients and those in whom the duration of dislocation was <45 days.

PMID- 24014780
TI  - Joint hypermobility and anterior cruciate ligament injury.
AB  - PURPOSE. To compare the rates of joint hypermobility in patients with and without
      anterior cruciate ligament (ACL) injury. METHODS. Records of 135 men and 75 women
      (mean age, 24.6 years) who underwent ACL reconstructions were reviewed and
      compared with 55 male and 35 female controls with no knee injury. Joint
      hypermobility was evaluated by 2 examiners using the Beighton score. The maximum
      score was 9, and a score of 4 or greater was defined as hypermobility. RESULTS.
      The mean time from injury to presentation was 18 days. A non-contact mechanism of
      injury was more common. The inter-observer reliability was 0.7. 127 (60.5%) of
      the patients with ACL injury and 23 (25.5%) of the controls had hypermobility
      (p<0.01). Among them, 58% and 24% were men and 65% and 29% were women,
      respectively. Female gender was associated with hypermobility. Patients with ACL
      injury were more likely to have joint hypermobility with an odds ratio of 4.46.
      CONCLUSION. Joint hypermobility was more common in patients with ACL injury. 

PMID- 24014781
TI  - Correlation between trochlear dysplasia and anterior cruciate ligament injury.
AB  - PURPOSE. To evaluate the correlation between trochlear dysplasia and anterior
      cruciate ligament (ACL) injury METHODS. Magnetic resonance images (MRIs) of 95
      knees in 54 males and 36 females aged 4 to 74 (mean, 28) years who had anterior
      knee pain and suspected ligamentous injury were reviewed. The MRIs were
      independently reviewed by 2 musculoskeletal radiologists on 2 occasions.
      According to the Dejour classification, trochlear dysplasia was classified into
      types A, B, C, and D. Intra-articular injuries/ disorders of the patients
      included patellofemoral osteoarthritis, chondromalacia patella, meniscal tears,
      and ligamentous injuries. Intra- and inter-observer variability was calculated.
      RESULTS. 58 of the knees had trochlear dysplasia, 38 of which were Dejour type A.
      The intra- and inter-observer variability was good to excellent (Kappa=0.76-1).
      ACL tear was the most common injury (n=13). No ACL injury occurred in patients
      without trochlear dysplasia. The odds of having sustained an ACL injury were 8.8
      fold greater in Dejour type-A knees than in non-type-A knees (p=0.023).
      CONCLUSION. Dejour type-A trochlear dysplasia was associated with ACL injuries. 

PMID- 24014782
TI  - Using the transverse acetabular ligament as a landmark for acetabular
      anteversion: an intra-operative measurement.
AB  - PURPOSE. To measure the transverse acetabular ligament (TAL) anteversion in hips
      with severe deformity, using fluoroscopy-computed tomographic navigation.
      METHODS. 31 hips in 10 men and 19 women aged 40 to 78 (mean, 58.7) years who
      underwent total hip arthroplasty for primary osteoarthritis (n=6) or
      osteoarthritis secondary to developmental hip dysplasia (n=19) or congenital hip
      dislocation (n=6) were included. The severity of hip dislocation was classified
      according to the Crowe classification; 15 hips were grade 1, 7 were grade 2, 3
      were grade 3, and 6 were grade 4. The TAL anteversion was measured using
      fluoroscopy-computed tomographic navigation. The difference in TAL anteversion
      between non-dislocated hips (Crowe grade 1, n=15) and dislocated hips (Crowe
      grades 2-4, n=16) was compared. RESULTS. In all 31 hips, the TAL could be
      visualised intra-operatively. No patient reported severe pain, early wear,
      loosening, or dislocation after 2 years. The mean TAL anteversion and inclination
      angles measured by the navigation system were 26.5 (SD, 8.9; range, 8-42) degrees
      and 41.5 (SD, 4.6; range, 32-49) degrees, respectively. 22 of the 31 hips were in
      the safe zone. TAL anteversion in non-dislocated and dislocated hips was not
      significantly different. Inter- and intra-observer mean absolute differences in
      TAL anteversion were 0.3 and 0.4 degree, respectively. CONCLUSION. The TAL is a
      useful anatomic landmark for total hip arthroplasty in dislocated hips. 

PMID- 24014783
TI  - Chromium level of salvaged blood in patients undergoing revision hip
      arthroplasty.
AB  - PURPOSE. To evaluate the chromium level of the salvaged blood in patients
      undergoing revision total hip arthroplasty (THA). METHODS. Records of 7 women and
      one man aged 54 to 83 (mean, 64.3) years who underwent revision THA for aseptic
      loosening of the acetabular component (n=6), osteolysis of the acetabulum (n=1),
      or migration of the outer head (n=1) were reviewed, as were 2 controls who
      underwent primary THA. The initial THA entailed a metal-on-metal prosthesis
      (n=4), a metal-on-polyethylene prosthesis (n=3), and a bipolar head prosthesis
      (n=1). Chromium levels in the preoperative peripheral blood and intraoperative
      salvaged blood were measured using atomic absorption analysis. RESULTS. For
      controls and the patient with a bipolar head prosthesis, the mean chromium level
      in salvaged blood was 0.4 (range, 0.2-0.6) micrograms/l, which was significantly
      lower than that in the remaining 7 patients undergoing revision THA (mean, 5.6
      micrograms/l; range, 1.2-9.8 micrograms/l). CONCLUSION. Salvaged blood of
      patients with a metal-on-metal prosthesis undergoing revision THA contained
      higher levels of chromium. 

PMID- 24014784
TI  - One-stage long-stem total knee arthroplasty for arthritic knees with stress
      fractures.
AB  - PURPOSE. To evaluate the outcome of one-stage long-stem total knee arthroplasty
      (TKA) for patients with arthritic knees and tibiofemoral stress fractures.
      METHODS. Records of 11 men and 18 women aged 47 to 78 (mean, 66) years who
      underwent fixed-bearing posterior-stabilised TKA for osteoarthritis or rheumatoid
      arthritis of the knee with tibial (n=31) and femoral (n=3) stress fractures were
      reviewed. All the tibial fractures involved the proximal half. There were 7
      associated fibular stress fractures. Of the 31 knees with tibial stress
      fractures, 26 and 5 manifested varus and valgus deformity, respectively. RESULTS.
      The mean follow-up period was 51 (range, 24-96) months. The mean tibiofemoral
      angle improved from 23.2 to 1.9 degrees varus. The mean Knee Society knee score
      improved from 38.5 (range, 15- 63) to 89.6 (range, 80-95) [p<0.05]. The mean Knee
      Society functional score improved from 25.5 (range, 0-40) to 86.5 (range, 60-100)
      [p<0.05]. All fractures were united at the last follow-up. No complications were
      encountered. CONCLUSION. One-stage long-stem TKA restores limb alignment and
      facilitates fracture healing, with excellent outcome. 

PMID- 24014785
TI  - Computed tomography-guided core needle biopsy versus incisional biopsy in
      diagnosing musculoskeletal lesions.
AB  - PURPOSE. To compare computed tomography (CT)- guided core needle biopsy (CNB)
      with incisional biopsy in diagnosing musculoskeletal lesions. METHODS. 62 men and
      50 women aged 12 to 83 (mean, 45) years who underwent a CT-guided CNB were
      compared with 31 men and 33 women aged 9 to 81 (mean, 53) years who underwent an
      incisional biopsy. All specimens had final pathology report to compare with.
      Comparisons were made in terms of (1) diagnostic rate, (2) accuracy in
      distinguishing benign from malignant lesions, (3) accuracy in distinguishing low-
      from high-grade sarcomas, (4) accuracy for histological diagnosis, and (5)
      complication and repeated biopsy rates. RESULTS. The diagnostic rate of CT-guided
      CNB and incisional biopsy was not significantly different (92.9% vs. 96.9%,
      p=0.33), nor were the accuracy in distinguishing benign from malignant lesions
      (100% vs. 98.4%, p=0.37), the accuracy in distinguishing low- from high-grade
      sarcomas (100% vs. 100%, p=1.00), the accuracy for specific diagnosis (75.9% vs.
      85.2%, p=0.17), the repeated biopsy rate (6.3% vs. 4.7%, p=0.75), and the
      complication rate (0.9% vs. 4.7%, p=0.14). The accuracy for specific diagnosis
      was higher for bone than soft-tissue lesions for both CT-guided CNB (87.0% vs.
      59.5%, p=0.002) and incisional biopsy (87.0% vs. 77.3%, p=0.43). The accuracy of
      CT-guided CNB for specific diagnosis of benign soft-tissue tumours as well as
      infection and inflammation was relatively low. CONCLUSION. CT-guided CNB is safe,
      easy to perform, efficient, and less invasive, and should be considered as a
      first-line biopsy for musculoskeletal lesions. 

PMID- 24014786
TI  - Treating giant cell tumours with curettage, electrocautery, burring, phenol
      irrigation, and cementation.
AB  - PURPOSE. To report on 23 patients with giant cell tumour (GCT) of the femur or
      tibia treated with curettage, electrocautery, burring, phenol irrigation, and
      cementation. METHODS. Records of these 14 men and 9 women aged 22 to 38 (mean,
      31) years were reviewed. The most common site involved was the distal femur
      (n=13), followed by proximal tibia (n=8), proximal femur (n=1), and distal tibia
      (n=1). The lesions were classified as grade I (n=3), grade II (n=18), and grade
      III (n=2). Based on histology, the tumour stage was classified as grade I (n=5)
      and grade II (n=18). Two of these patients had recurrences, which were initially
      treated with simple curettage and bone grafting of the distal femur and distal
      tibia. RESULTS. The mean follow-up period was 5.7 (range, 2.5-10.1) years. 14 of
      the 23 patients were followed up for over 10 years. No patient developed any
      local recurrence, remote metastasis, or complication related to surgery or
      adjuvant therapy. CONCLUSION. Combined treatment entailing curettage,
      electrocautery, burring, phenol irrigation, and cementation was effective in
      treating GCT of bone. 

PMID- 24014787
TI  - Antibiotic-coated pins for prevention of pin-tract infection: a rabbit study.
AB  - PURPOSE. To evaluate the efficacy of antibiotic-coated pins for prevention of pin
      tract infection in a rabbit model. METHODS. 10 rabbits were divided into 2
      groups. A unilateral external fixator was applied to the tibia with 4 self-taping
      1.8-mm pins. In the test group, pins were coated with hydroxyapatite and
      antibiotic. In the control group, pins were not coated. All pins were then placed
      in Staphylococcus aureus- containing media. At postoperative day 5, all 40 pin
      sites were subcutaneously inoculated with S aureus. The sites were clinically
      examined for signs of pin tract infection. Nine days later, a piece of soft
      tissue around the pin site was harvested for microbiologic examination. RESULTS.
      In the test group, all except one pin sites appeared clean and without clinical
      infection, and the culture media remained clear. In the control group, all pin
      sites showed evidence of clinical infection and yielded positive cultures, and
      the culture media became dark indicating growth of S aureus. CONCLUSION.
      Antibiotic-coated pins were effective in preventing pin tract infection. 

PMID- 24014788
TI  - Collagen expression in various degenerative meniscal changes: an
      immunohistological study.
AB  - PURPOSE. To examine changes in acid mucopolysaccharides and collagen expression
      during meniscal degeneration, tearing, and repair, using menisci excised from
      knee joint surgeries. METHODS. Menisci excised from 23 patients aged 15 to 80
      years who underwent meniscal surgery for flap and bucket handle tears (n=11) and
      total knee arthroplasty (TKA) for osteoarthritis (n=12) were examined
      histologically. Staining images were converted to greyscale images to measure the
      mean grey levels, which indicated densitometry. Comparisons were made between
      acutely injured menisci and menisci with and without degeneration (from patients
      with osteoarthritis) in terms of acid mucopolysaccharides, collagen types I, II,
      and III expression. RESULTS. In menisci with no degeneration, acid
      mucopolysaccharides, collagen types I and II were expressed throughout the entire
      meniscus except for the circulating area. Collagen type III was intensely
      expressed at the exterior peripheral border and on the surface. During
      progression of meniscal degeneration, the expression of acid mucopolysaccharides
      increased, and the expression of collagen types I, II, and III decreased. In
      acutely injured menisci, collagen types II and III disappeared first, followed by
      collagen type I, resulting in the abrogation of fibre construction. CONCLUSION.
      In normal menisci, acid mucopolysaccharides and collagen types I, II, and III
      were well-balanced, and meniscal function was maintained. When the limits of
      repair were exceeded, the meniscus tissue deteriorated owing to the disappearance
      of collagen types II and III and a decrease in collagen type I, resulting in the
      abrogation of meniscus fabric construction. 

PMID- 24014789
TI  - Calamine lotion to reduce skin irritation in children with cast immobilisation.
AB  - PURPOSE. To evaluate the effect of calamine lotion in reducing skin irritation in
      children with cast immobilisation and to identify factors correlating with skin
      irritation. METHODS. 250 children aged 6 to 15 years who underwent cast
      immobilisation for limb fractures were assigned into calamine (n=122) and non
      calamine (n=128) groups. Data were collected at the time the cast was applied and
      removed. Potential confounders (gender, age, race, medical history, drug allergy,
      cast type, duration of casting, and extent of itch prior to casting) were
      identified. Each patient graded his levels of itch, sweat, and heat using a 5
      point scale (with 5 indicating most severe). The on-duty plaster technician
      recorded the presence and type of skin lesions (blisters, wounds, or others)
      during cast removal. RESULTS. Children in the calamine group were less likely to
      develop skin lesions (1 vs. 9, odds ratio [OR]=0.115, p=0.009), had less itch
      during casting (mean difference=0.74, p<0.0001), had a greater decrease in the
      itch level (mean difference=0.84, p<0.0001), and had lower sweat levels
      (p=0.048). After adjusting for confounders, the chance of developing skin lesions
      remained lower in the calamine group (OR=0.063, p=0.003). Being an older child
      and having shorter duration of casting were associated with presence of skin
      lesions. The odds for having skin lesions increased by 39.2% per year increase in
      age (OR=1.392, p=0.04) and decreased by 9.4% per day increase in casting duration
      (OR=0.906, p=0.03). The decrease in itch level remained significantly greater in
      the calamine group after adjusting for confounders (p<0.0001). CONCLUSION.
      Calamine lotion may reduce skin irritation in children with full casts. 

PMID- 24014790
TI  - Review article: Regenerative techniques for repair of rotator cuff tears.
AB  - The failure rate of rotator cuff repair is high. Regenerative techniques using
      material scaffolds, stem cells, and growth factors help augment repair and
      regenerate tissue. We reviewed the literature of various regenerative techniques
      in terms of (1) enhancing the repair process, (2) tissue regeneration, (3)
      mechanical strength, and (4) clinical outcome. 

PMID- 24014791
TI  - Review article: Treatment for Achilles tendon ruptures in athletes.
AB  - Treatment for Achilles tendon ruptures in athletes is controversial. Surgical
      fixation has lower rates of re-rupture and confers increased strength and
      function, whereas conservative treatment has lower risks of wound complications.
      We review the literature on the optimal treatment for Achilles tendon rupture in
      athletes. 

PMID- 24014792
TI  - Review article: Joint aspiration for diagnosis of periprosthetic infection.
AB  - Joint aspiration is a reliable tool for diagnosis of periprosthetic infection.
      There are different indications, techniques, and approaches for joint aspiration.
      We recommend that it be performed selectively when infection is suspected
      clinically. The specimens should be interpreted based on the results of the
      culture as well as the white cell count and differential. Specimen collection,
      transport, and analysis should be prompt to ensure yield accuracy. 

PMID- 24014793
TI  - Two-stage knee arthrodesis using a cemented modular tumour replacement system for
      recalcitrant septic proximal tibial non-union: a case report.
AB  - Knee arthrodesis is an alternative to amputation for treating recalcitrant septic
      non-union of the proximal tibia with bone loss, soft-tissue compromise, and knee
      joint involvement. Nonetheless, arthrodesis is difficult to achieve if bone loss
      is massive, and the septic environment can result in failed bone fusion. We
      report on a 77-year-old man with massive bone loss secondary to recalcitrant
      septic non-union who underwent radical bone resection, followed by knee
      arthrodesis using a cemented modular intercalary megaprosthesis in conjunction
      with a microvascularised flap in 2 stages. 

PMID- 24014794
TI  - Rhinosporidiosis of the left wrist joint: a case report.
AB  - Rhinosporidiosis is a chronic granulomatous disease caused by Rhinosporidium
      seeberi. It usually occurs in the mucous membranes of nose, nasopharynx, and
      eyes, and less commonly in extra nasal sites such as skin, bones, genitalia, and
      even the internal organs. Rhinosporidiosis occurs in the wrist joint with
      isolated bony involvement is rare. We report one such case in a 50-year-old man
      who presented with a non-tender, fixed swelling over his anterolateral aspect of
      left forearm. Radiography and computed tomography showed a lytic destructive
      lesion involving the distal radius, ulna, carpals, and base of metacarpals.
      Biopsy revealed features of rhinosporidiosis. The patient underwent below-elbow
      amputation. 

PMID- 24014795
TI  - Bosworth fracture-dislocation of the ankle: a case report.
AB  - Bosworth fracture-dislocation of the ankle is a rare injury in which the proximal
      fibular fragment is entrapped behind the tibia. Closed reduction is extremely
      difficult to achieve. Early open reduction and internal fixation enables a better
      outcome by minimising soft-tissue damage. We report on a 36-year-old man who
      underwent open reduction and internal fixation for a Bosworth fracture
      dislocation of the ankle complicated by severe soft-tissue swelling and an
      impending risk of skin necrosis after failed closed reduction. 

PMID- 24014796
TI  - A subtrochanteric femoral fracture 15 years after radiotherapy: a case report.
AB  - Pathological fracture is a rare but serious complication of radiotherapy. We
      report on a 44-year-old man who presented with a subtrochanteric femoral fracture
      15 years after radiotherapy for a soft-tissue sarcoma in the thigh. We discuss
      its potential causes, a scoring system to identify high-risk patients for
      prophylactic intramedullary nailing of the femur, and radiographic signs to
      identify an impending insufficiency fracture. 

PMID- 24014797
TI  - Legg-Calve-Perthes disease in two generations of male family members: a case
      report.
AB  - Legg-Calve-Perthes disease (LCPD) is a type of avascular necrosis of the femoral
      head occurring mainly in male children and causing early osteoarthritis. We
      report 2 generations of 4 male family members with LCPD-like features and
      mutation of the COL2A1 gene of the 12q13 chromosome. If LCPD occurs in any family
      member, we recommend genetic analysis and counselling as well as early
      radiological screening of related children. 

PMID- 24014799
TI  - Percutaneous autologous bone marrow injections for delayed or non-union of bones.

PMID- 24014798
TI  - Loeys-Dietz syndrome with bilateral radial head dislocations: a case report.
AB  - Loeys-Dietz syndrome is characterised by vascular aneurysms, hypertelorism, and a
      bifid uvula. We report on an 11-year-old boy with Loeys-Dietz syndrome who
      presented with bilateral radial head dislocations and severe osteopaenia with
      changes of avascular necrosis in both hips causing an out-toeing, wide gait.
      Considering the poor prognosis for elbow movement and possible radial head
      dysplasia, surgical reduction of the radial heads was deferred. A subtrochanteric
      de-rotation osteotomy of the left hip was performed to improve the gait. 

PMID- 24014801
TI  - An Overview of Hepatitis B Virus Surface Antigen Mutant in the Asia Pacific.
AB  - Hepatitis B virus infection is a serious health problem worldwide, and more than
      350 million people are chronic carriers, constituting a major global threat.
      Southeast Asia and the Western Pacific have the highest levels of endemicity in
      the world, with an estimated seroprevalence ranging between 2% and 31%. Mutations
      in the hepatitis B surface antigen (HBsAg) have been reported in many parts of
      the world but are most common in Asian infants; such mutants have several
      clinical effects, such as the development of hepatocellular carcinoma. Diagnostic
      failures by commercial assays have reduced the diagnostic effectiveness of HBsAg
      detection. For example the substitution of an amino acid in the major hydrophilic
      region of the S gene reduces the binding of hepatitis B surface antibodies
      leading to immune escape. The safety of blood transfusion may be compromised by
      current screening tests due to escape from being neutralised by antibodies
      induced by HBsAg mutants, and undetectable levels of viral surface protein. Data
      on the epidemiology of HBsAg mutation in Asia Pacific are scant; however, this
      manuscript has reviewed the available information on the epidemiology of HBsAg
      mutation in Asia Pacific. 

PMID- 24014802
TI  - Acute direct current cardioversion: how 'dangerous' is it?

PMID- 24014803
TI  - Navigated DENSE strain imaging for post-radiofrequency ablation lesion assessment
      in the swine left atria.
AB  - AIMS: Prior work has demonstrated that magnetic resonance imaging (MRI) strain
      can separate necrotic/stunned myocardium from healthy myocardium in the left
      ventricle (LV). We surmised that high-resolution MRI strain, using navigator-echo
      triggered DENSE, could differentiate radiofrequency ablated tissue around the
      pulmonary vein (PV) from tissue that had not been damaged by radiofrequency
      energy, similarly to navigated 3D myocardial delayed enhancement (3D-MDE).
      METHODS AND RESULTS: A respiratory-navigated 2D-DENSE sequence was developed,
      providing strain encoding in two spatial directions with 1.2 * 1.0 * 4 mm(3)
      resolution. It was tested in the LV of infarcted sheep. In four swine, incomplete
      circumferential lesions were created around the right superior pulmonary vein
      (RSPV) using ablation catheters, recorded with electro-anatomic mapping, and
      imaged 1 h later using atrial-diastolic DENSE and 3D-MDE at the left atrium/RSPV
      junction. DENSE detected ablation gaps (regions with >12% strain) in similar
      positions to 3D-MDE (2D cross-correlation 0.89 +/- 0.05). Low-strain (<8%) areas
      were, on average, 33% larger than equivalent MDE regions, so they include both
      injured and necrotic regions. Optimal DENSE orientation was perpendicular to the
      PV trunk, with high shear strain in adjacent viable tissue appearing as a
      sensitive marker of ablation lesions. CONCLUSIONS: Magnetic resonance imaging
      strain may be a non-contrast alternative to 3D-MDE in intra-procedural monitoring
      of atrial ablation lesions.

PMID- 24014804
TI  - Clinical response with adaptive CRT algorithm compared with CRT with
      echocardiography-optimized atrioventricular delay: a retrospective analysis of
      multicentre trials.
AB  - AIMS: Adaptive cardiac resynchronization therapy (aCRT) is a novel algorithm for
      CRT pacing that provides automatic ambulatory selection between synchronized left
      ventricular (LV) or bi-ventricular (BiV) pacing and optimization of
      atrioventricular (AV) and inter-ventricular (VV) delays based on periodic
      measurement of intrinsic conduction. We aimed to compare the clinical response
      between aCRT and standard CRT in historical trials. METHODS AND RESULTS: The
      treatment arm of the aCRT trial was compared with a pooled historical control
      (HC) derived from the CRT arms of four clinical trials (MIRACLE, MIRACLE ICD,
      PROSPECT, and InSync III Marquis) with respect to the proportion of patients who
      had an improved clinical composite score (CCS) at the 6-month follow-up. Patients
      in the HC underwent echocardiography-guided AV optimization after the implant. A
      propensity score model was used to adjust for 22 potential baseline confounders
      of the effect of CRT. Patients were stratified into quintiles according to the
      propensity score and the adjusted absolute treatment effect was obtained by
      averaging estimates across these quintiles. The propensity score model included
      751 patients (aCRT: 266, historical trials: 485). The adjusted absolute
      difference in percent improved in CCS between the aCRT and HC arms was 11.9% [95%
      confidence interval (CI): 2.7-19.2%] favouring aCRT. The patients in the aCRT
      group were significantly more likely to have an improved CCS than the patients in
      the HC (odds ratio = 1.65, 95% CI: 1.1-2.5). CONCLUSION: The aCRT algorithm may
      be associated with additional improvement in clinical response compared with
      historical CRT with echocardiographic AV optimization.

PMID- 24014805
TI  - Muscle afferents and cardiorespiratory control: the Birmingham connection.
AB  - NEW FINDINGS: What is the topic of this review? This brief review describes the
      work of Professor John Coote and colleagues at the University of Birmingham,
      which has contributed to understanding of the role of muscle afferent involvement
      in cardiorespiratory control in exercise. What advances does it highlight? The
      seminal findings of John Coote's early work are highlighted, as well as more
      recent developments in the field, especially the role of muscle afferents in the
      control of human ventilation during exercise. Through the work of John Coote,
      research into the role of muscle afferent involvement in cardiorespiratory
      control has had strong links with Birmingham since the late 1960s. This brief
      review gives an historical background to John's early work and how his research
      and mentorship of colleagues continues to have a profound influence on the field
      today.

PMID- 24014806
TI  - Pneumatic antishock garment inflation activates the human sympathetic nervous
      system by abdominal compression.
AB  - Pneumatic antishock garments (PASG) have been proposed to exert their blood
      pressure-raising effect mechanically, i.e. by increasing venous return and
      vascular resistance of the lower body. We tested whether, alternatively, PASG
      inflation activates the sympathetic nervous system. Five men and four women wore
      PASG while mean arterial pressure (MAP), muscle sympathetic nerve activity
      (MSNA), heart rate and stroke volume were measured. One leg bladder (LEG) and the
      abdominal bladder (ABD) of the trousers were inflated individually and in
      combination (ABD+LEG), at 60 or 90 mmHg for 3 min. By the end of 3 min of
      inflation, conditions that included the ABD region caused significant increases
      in MAP in a dose-dependent fashion (7 +/- 2, 8 +/- 3, 14 +/- 4 and 13 +/- 5 mmHg
      for ABD60, ABD+LEG60, ABD90 and ABD+LEG90, respectively, P < 0.05). Likewise,
      inflation that included ABD caused significant increases in total MSNA compared
      with control values [306 +/- 70, 426 +/- 98 and 247 +/- 79 units for ABD60, ABD90
      and ABD+LEG90, respectively, P < 0.05 (units = burst frequency * burst
      amplitude]. There were no changes in MAP or MSNA in the LEG-alone conditions. The
      ABD inflation also caused a significant decrease in stroke volume (-11 +/- 3 and 
      10 +/- 3 ml per beat in ABD90 and ABD+LEG90, respectively, P < 0.05) with no
      change in cardiac output. Neither cardiopulmonary receptor deactivation nor
      mechanical effects can account for a slowly developing rise in both sympathetic
      activity and blood pressure during ABD inflation. Rather, these data provide
      direct evidence that PASG inflation activates the sympathetic nervous system
      secondarily to abdominal, but not leg, compression.

PMID- 24014807
TI  - Effect of inspiratory muscle fatigue on exercise performance taking into account
      the fatigue-induced excess respiratory drive.
AB  - Inspiratory muscle fatigue (IMF) is suggested to compromise exercise performance,
      possibly via a respiratory muscle metaboreflex that impairs blood flow to working
      muscles, thereby accelerating the development of fatigue in these muscles.
      Cycling with IMF has also been associated with an excess ventilatory response,
      which could per se impair performance. Therefore, the present study investigated
      whether prior-induced IMF would affect subsequent cycling performance via
      increased quadriceps muscle fatigue alone and whether fatigue-induced excess
      ventilation would contribute to this impairment. Fourteen healthy male subjects
      (peak oxygen uptake, 57.0 +/- 5.5 ml min(-1) kg(-1)) cycled to exhaustion at 85%
      of their maximal work output with prior-induced IMF (PF-EX) and without prior
      induced IMF (C-EX). Subjects then cycled twice for the duration of PF-EX but
      without prior IMF, once with spontaneous breathing (C-ISO) and once with
      breathing coached to match PF-EX ventilation (MATCH-ISO). Inspiratory muscle
      (P(tw)) and quadriceps muscle contractility (Q(tw)) was assessed via magnetic
      nerve stimulation before and after exercise. The time to exhaustion in the PF-EX
      conditions was significantly reduced by 14% compared with C-EX. The reduction in
      P(tw) and Q(tw) was greater after PF-EX (P(tw), 17.3 +/- 9.7%; Q(tw), 32.0 +/-
      10.8%) than after MATCH-ISO (P(tw), 10.8 +/- 10.3%; Q(tw), 23.3 +/- 15.2%; P <
      0.05), which may explain the increased perception of exertion and earlier task
      failure with prior-induced IMF. The augmented ventilatory drive had no effect on
      reductions in P(tw) and Q(tw) after MATCH-ISO compared with C-ISO. Thus, prior
      induced IMF reduces exercise performance, probably as a result of the increased
      quadriceps muscle fatigue and thus greater perception of exertion independent of
      the excess respiratory drive when cycling with fatigued inspiratory muscles.

PMID- 24014808
TI  - Vagal modulation of cardiac ventricular arrhythmia.
AB  - NEW FINDINGS: What is the topic of this review? This article addresses the
      relationship between vagus nerve activity and malignant ventricular arrhythmias.
      It focuses on the clinical association of an impaired vagal tone in cardiac
      disease states with high mortality from sudden cardiac death and the potential
      underlying mechanisms. What advances does it highlight? The article summarizes
      the mounting evidence that vagal innervation in the cardiac ventricle plays a key
      direct role in the prevention of the initiation of ventricular fibrillation. Data
      are presented on the role that nitric oxide plays in mediating the effects of
      vagal protection against ventricular fibrillation, supporting the notion that a
      separate non-muscarinic, nitrergic population of vagal neurons is responsible for
      this protection. Sudden cardiac death remains a significant unresolved clinical
      problem, with many of the deaths being due to malignant ventricular arrhythmias.
      Markers of abnormal autonomic function have been shown to be strong prognostic
      predictors, highlighting the important relationship between reduced vagal tone
      and malignant ventricular arrhythmias, such as ventricular fibrillation, in
      cardiac patients. Exploring the mechanisms underlying the autonomic modulation of
      ventricular fibrillation, my group has shown that vagus nerve stimulation
      protects against ventricular fibrillation in the innervated isolated heart
      preparation. We have provided direct evidence that nitric oxide is released in
      the ventricle with cervical vagus nerve stimulation and NO mediates the
      antifibrillatory actions of vagus nerve stimulation in the ventricle. Classical
      physiology teaches that vagal postganglionic nerves modulate the heart via
      acetylcholine acting at muscarinic receptors and, dogmatically, that there is
      little vagal effect in the ventricle, as innervation was believed to be sparse.
      Mounting evidence from many species now supports the presence of a rich vagal
      innervation in the ventricle. Data from my group showing that the protective
      actions of vagus nerve stimulation against ventricular fibrillation and NO
      release are preserved in the presence of muscarinic block support the notion that
      a population of nitrergic neurons could be responsible. This potentially
      exploitable downstream pathway together with the availability of vagus nerve
      stimulators make it an exciting time to investigate the development of an
      effective strategy of vagal protection against ventricular fibrillation in the
      clinical setting.

PMID- 24014809
TI  - Ontogeny and control of the heart rate power spectrum in the last third of
      gestation in fetal sheep.
AB  - Power spectral analysis of fetal heart rate variability has been proposed to
      provide a non-invasive estimate of autonomic balance. However, there are few
      systematic data before birth. We therefore examined developmental changes in the
      frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high
      frequencies (0.15-0.4 Hz), as well as the ratio of low- to high-frequency power
      (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n
      = 7) and 0.8 gestational age (ga; n = 11). In a second study, 0.8 ga fetuses
      received either atropine (4.8 mg bolus, then 4.8 mg h(-1) for 30 min, n = 6) or 6
      hydroxydopamine (20 mg ml(-1) at 2.5 ml h(-1) for 3 h; n = 9). Data were analysed
      by sleep state, defined by low-voltage-high-frequency (LV) or high-voltage-low
      frequency (HV) EEG. Total spectral power increased with gestational age (P <
      0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF
      were significantly higher during HV than LV sleep (P < 0.05). Consistent with
      this, although total spectral power was not significantly greater during HV
      sleep, there was a significant interaction between sleep state and frequency band
      (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were
      associated with an overall reduction in spectral power but no significant effect
      on the LF/HF ratio. This study does not support substantial, consistent
      differences between the frequencies of sympathetic and parasympathetic activity
      in late-gestation fetal sheep. 

PMID- 24014810
TI  - In memoriam: Seymour Lieberman, hormonologist, chemist and humanist (1916-2012)
      National Academy of Sciences of the United States of America, member, and
      Endocrine Society, president, 1974-1975.

PMID- 24014812
TI  - The normal TSH reference range: what has changed in the last decade?

PMID- 24014811
TI  - Approach to male infertility and induction of spermatogenesis.
AB  - Male subfertility is common, and it causes significant duress to couples.
      Although the most common cause of male subfertility is idiopathic failure of
      spermatogenesis, a significant percentage of male subfertility is medically
      treatable. Compared to reproductive specialists, endocrinologists may see a
      population of men that have a higher prevalence of treatable causes of
      subfertility including sexual disorders, endocrinopathies, obesity, drugs, and
      ejaculatory dysfunction. Seminal fluid analysis is the most important diagnostic
      study, and at least 2 samples should be analyzed. All patients with sperm
      concentrations < 10 million/mL due to idiopathic spermatogenic defects should be
      referred for genetic counseling and karyotyping; most experts also recommend that
      these patients be tested for Y chromosomal microdeletions. For most men with low
      sperm concentrations due to gonadotropin deficiency, gonadotropin therapy
      effectively increases spermatogenesis. The endocrinologist must recognize when to
      use medical therapy to stimulate spermatogenesis and when to refer for
      consideration of assisted reproductive technology. 

PMID- 24014813
TI  - The J-curve limbo: how low can you go?

PMID- 24014814
TI  - Normal long-term health for infants of diabetic mothers: can we achieve it?

PMID- 24014815
TI  - Ethnic differences and beta-cell changes.

PMID- 24014819
TI  - PCOS: what teens need to know.

PMID- 24014822
TI  - Crossing borders: one world, global health.

PMID- 24014820
TI  - Aging enhances release of exosomal cytokine mRNAs by Abeta1-42-stimulated
      macrophages.
AB  - Amyloid-beta1-42 (Abeta) peptide effects on human models of central nervous
      system (CNS)-patrolling macrophages (Ms) and CD4 memory T-cells (CD4-Tms) were
      investigated to examine immune responses to Abeta in Alzheimer's disease. Abeta
      and lipopolysaccharide (LPS) elicited similar M cytokine and exosomal mRNA (ex
      mRNA) responses. Abeta- and LPS-stimulated Ms from 20 >=65-yr-old subjects
      generated significantly more IL-1, TNF-alpha, and IL-6, but not IL-8 or IL-12,
      and significantly more ex-mRNAs for IL-6, TNF-alpha, and IL-12, but not for IL-8
      or IL-1, than Ms from 20 matched 21- to 45-yr-old subjects. CD4-Tm generation of
      IL-2, IL-4, and IFN-gamma and, for young subjects, IL-10, but not IL-6, evoked by
      Abeta was significantly lower than with anti-T-cell antigen receptor antibodies
      (Abs). Abs significantly increased all CD4-Tm ex-mRNAs, but only IL-2 and IL-6 ex
      mRNAs were increased by Abeta. There were no significant differences between
      cytokine and ex-mRNA responses of CD4-Tms from the old compared to the young
      subjects. M-derived serum exosomes from the old subjects had significantly higher
      IL-6 and IL-12 ex-mRNA levels than those from the young subjects, whereas there
      were no differences for CD4-Tm-derived serum exosomes. An Abeta level relevant to
      neurodegeneration elicited broad M cytokine and ex-mRNA responses that were
      significantly greater in the old subjects, but only narrow and age-independent
      CD4-Tm responses.

PMID- 24014823
TI  - Size matters! Impact of age, sex, height, and weight on the normal heart size.
AB  - BACKGROUND: Therapeutic decisions in cardiology are determined frequently by
      cardiac chamber size. To decide whether cardiac dimensions are still in the
      normal range, reliable reference values are needed. However, published reference
      values mostly refer to historical cohorts using motion-mode measurements and have
      not been adjusted for sex or age. The impact of body size was only vaguely
      addressed. The importance of such adjustments is illustrated by studies, which
      show that smaller individuals and women are at risk of delayed treatment and
      impaired outcome when currently used reference values are applied. The aim of the
      present study was to assess the impact of body size, sex, and age on the normal
      heart size. METHODS AND RESULTS: We prospectively studied 622 individuals (52.7%
      women; 17-91 years; 143-200 cm; 32-240 kg) without cardiac disease by standard
      transthoracic echocardiography. Multivariable linear regression analyses of the
      impact of sex, age, height, and weight on cardiac chamber size were performed. By
      multivariable regression analysis (n=500), all 4 variables independently
      influenced cardiac chamber size. The validity of cardiac dimensions predicted by
      the regression model was tested prospectively in a validation cohort (n=122). A
      calculator is proposed that estimates cardiac dimensions on the basis of the
      regression analysis. CONCLUSIONS: Sex, height, weight, and age significantly
      affect the normal heart size. These parameters need to be considered when cutoff
      values indicating the need for treatment or even surgery are established.

PMID- 24014824
TI  - Transient ischemic dilation in patients with diabetes mellitus: prognostic value
      and effect on clinical outcome after coronary revascularization.
AB  - BACKGROUND: We prospectively evaluated the incremental prognostic value of
      transient ischemic dilation (TID) in patients with type 2 diabetes mellitus
      during long-term follow-up and estimated cardiac death and nonfatal myocardial
      infarction (MI) using traditional approaches of prognostication to more recent
      methods. METHODS AND RESULTS: A total of 672 consecutive diabetic patients with
      available rest and stress gated myocardial perfusion single-photon emission
      computed tomographic data were enrolled. Stepwise Cox regression analysis was
      used to estimate cardiac death or nonfatal MI. Risk reclassification was
      calculated, and an exploratory analysis was performed to evaluate the effect of
      coronary revascularization on event-free survival. Adding TID to a multivariable
      model, including age, history of MI, stress type, poststress left ventricular
      ejection fraction, and stress-induced myocardial ischemia, improved
      discrimination of cardiac death or nonfatal MI (C statistic, 0.74-0.82; P=0.01;
      adjusted hazard ratio, 3.6; P<0.0001) and led to a net reclassification
      improvement of 0.39 (95% confidence interval, 0.14-0.64). Revascularization had a
      significant effect on event-free survival (adjusted hazard ratio, 0.25; P<0.001),
      with significant interactions between revascularization and poststress left
      ventricular ejection fraction, revascularization and stress-induced myocardial
      ischemia, and revascularization and TID (all P<0.01) CONCLUSIONS: TID provides
      independent and incremental prognostic information for the prediction of cardiac
      death or nonfatal MI in patients with diabetes mellitus. The addition of TID to a
      prediction model based on cardiovascular risk factors, left ventricular ejection
      fraction, and ischemia significantly improves risk discrimination and
      reclassification for incident cardiac events. The effect of revascularization
      seems to be influenced by left ventricular systolic function, stress-induced
      myocardial ischemia, and TID.

PMID- 24014825
TI  - Functional significance of elevated mitral gradients after repair for
      degenerative mitral regurgitation.
AB  - BACKGROUND: We have observed that elevated mitral gradients can develop in some
      patients after mitral valve repair for degenerative mitral regurgitation. METHODS
      AND RESULTS: We screened 275 patients who had mitral valve repair involving >1
      leaflet scallop between October 2001 and July 2010. Mitral valve hemodynamics
      were assessed at rest and at peak exercise using the cycle ergometer. B-type
      natriuretic peptide levels were measured at rest and after exercise. The patients
      also performed a 6-minute walk test and short-form 36-Item Health Survey
      questionnaire. We enrolled 110 patients, with resting mean mitral diastolic
      gradient of <=3 mm Hg in 35 patients (group 1) and >3 mm Hg indicative of
      elevated mitral gradients in 75 patients (group 2). Posterior mitral leaflet
      plication (P=0.04) and the use of a complete mitral annuloplasty ring (P<0.0001)
      were associated with elevated mitral gradients. Group 2 patients had larger left
      atrial volume (P=0.02), higher mitral gradients at peak exercise and higher
      pulmonary artery systolic pressure at rest and at peak exercise, and lower
      exercise capacity (101+/-40 versus 122+/-51 W; P=0.02). Group 2 patients also had
      higher B-type natriuretic peptide levels and lower scores in 3 short-form 36-Item
      Health Survey health concepts. Multivariate regression analyses showed that
      mitral valve area was an independent predictor of maximum exercise capacity
      (P=0.003). CONCLUSIONS: After mitral valve repair for degenerative mitral
      regurgitation, elevated mitral gradients is not uncommon and is associated with
      worse intracardiac hemodynamics, higher B-type natriuretic peptide levels, lower
      exercise capacity, and poorer quality of life. Further refinement in the surgical
      technique may reduce the incidence of this complication.

PMID- 24014826
TI  - Myocardial titin hypophosphorylation importantly contributes to heart failure
      with preserved ejection fraction in a rat metabolic risk model.
AB  - BACKGROUND: Obesity and diabetes mellitus are important metabolic risk factors
      and frequent comorbidities in heart failure with preserved ejection fraction.
      They contribute to myocardial diastolic dysfunction (DD) through collagen
      deposition or titin modification. The relative importance for myocardial DD of
      collagen deposition and titin modification was investigated in obese, diabetic
      ZSF1 rats after heart failure with preserved ejection fraction development at 20
      weeks. METHODS AND RESULTS: Four groups of rats (Wistar-Kyoto, n=11; lean ZSF1,
      n=11; obese ZSF1, n=11, and obese ZSF1 with high-fat diet, n=11) were followed up
      for 20 weeks with repeat metabolic, renal, and echocardiographic evaluations and
      hemodynamically assessed at euthanization. Myocardial collagen, collagen cross
      linking, titin isoforms, and phosphorylation were also determined. Resting
      tension (Fpassive)-sarcomere length relations were obtained in small muscle
      strips before and after KCl-KI treatment, which unanchors titin and allows
      contributions of titin and extracellular matrix to Fpassive to be discerned. At
      20 weeks, the lean ZSF1 group was hypertensive, whereas both obese ZSF1 groups
      were hypertensive and diabetic. Only the obese ZSF1 groups had developed heart
      failure with preserved ejection fraction, which was evident from increased lung
      weight, preserved left ventricular ejection fraction, and left ventricular DD.
      The underlying myocardial DD was obvious from high muscle strip stiffness, which
      was largely (+/-80%) attributable to titin hypophosphorylation. The latter
      occurred specifically at the S3991 site of the elastic N2Bus segment and at the
      S12884 site of the PEVK segment. CONCLUSIONS: Obese ZSF1 rats developed heart
      failure with preserved ejection fraction during a 20-week time span. Titin
      hypophosphorylation importantly contributed to the underlying myocardial DD.

PMID- 24014827
TI  - Do outcomes for patients with heart failure vary by emergency department volume?
AB  - BACKGROUND: Heart failure is a common Emergency Department (ED) presentation but
      whether ED volume influences patient outcomes is unknown. METHODS AND RESULTS:
      Retrospective cohort of all adults presenting to 93 EDs between 1999 and 2009
      with a most responsible diagnosis of heart failure (n=44 925 ED visits; mean age,
      76.4 years). Cases seen in low-volume EDs had less comorbidities and were less
      likely to be hospitalized (54.5%) than those seen in medium (61.8%; adjusted odds
      ratio [aOR] 1.16, [95% confidence interval {CI} 1.10-1.23]) or high-volume EDs
      (73.6%; aOR, 1.95 [95% CI, 1.83-2.07]). Of patients treated and released, low
      volume ED cases exhibited higher risk of death/hospitalization/ED visit in the
      subsequent 7 (22.0%) and 30 days (44.9%) than medium (16.3%; aOR, 0.81 [95% CI,
      0.73-0.90], and 35.3%; aOR, 0.79 [95% CI, 0.73-0.86]) or high-volume ED cases
      (13.0%; aOR, 0.69 [95% CI, 0.61-0.78], and 30.2%; aOR, 0.67 [95% CI, 0.61-0.74]).
      Of patients hospitalized at the time of their index ED visit, low-volume ED cases
      exhibited a higher risk of 30-day death/all-cause readmission (24.3%) than those
      seen in medium (21.9%; aOR, 0.83 [95% CI, 0.76-0.91]) or high-volume EDs (18.1%;
      aOR, 0.77 [95% CI, 0.70-0.85]). CONCLUSIONS: Low-volume EDs were more likely to
      discharge patients with heart failure home, but low-volume ED cases exhibited
      worse outcomes (driven largely by readmissions or repeat ED visits).
      Interventions to improve management of acute heart failure are required at low
      volume sites.

PMID- 24014828
TI  - Impact of ejection fraction on the clinical response to cardiac resynchronization
      therapy in mild heart failure.
AB  - BACKGROUND: Current guidelines recommend cardiac resynchronization therapy (CRT)
      in mild heart failure (HF) patients with QRS prolongation and ejection fraction
      (EF) <=30%. To assess the effect of CRT in less severe systolic dysfunction,
      outcomes in the REsynchronization reVErses Remodeling in Systolic left
      vEntricular dysfunction (REVERSE) study were evaluated in which patients with
      left ventricular (LV) ejection fraction (LVEF) >30% were included. METHODS AND
      RESULTS: The results of patients with baseline EF >30% (n=177) and those with EF
      <=30% (n=431), as determined by a blinded core laboratory, were compared. In the
      LVEF >30% subgroup, there was a trend for improvement in the clinical composite
      response with CRT ON versus CRT OFF (P=0.06) and significant reductions in LV end
      systolic volume index (-6.7 +/- 21.1 versus 2.1 +/- 17.6 mL/m(2); P=0.01) and LV
      mass (-20.6 +/- 50.5 versus 5.0 +/- 42.4 g; P=0.04) after 12 months. The time to
      death or first HF hospitalization was significantly prolonged with CRT (hazard
      ratio, 0.26; P=0.012). In the LVEF <30% subgroup, significant improvements in
      clinical composite response (P=0.02), reverse remodeling parameters, and time to
      death or first HF hospitalization (hazard ratio, 0.58; P=0.047) were observed.
      After adjusting for important covariates, the CRT ON assignment remained
      independently associated with improved time to death or first HF hospitalization
      (hazard ratio, 0.54; P=0.035), whereas there was no significant interaction with
      LVEF. CONCLUSIONS: Among subjects with mild HF, QRS prolongation, and LVEF >30%,
      CRT produced reverse remodeling and similar clinical benefit compared with
      subjects with more severe LV systolic dysfunction. CLINICAL TRIAL REGISTRATION-
      URL: http://www.clinicaltrials.gov. Unique identifier: NCT00271154.

PMID- 24014829
TI  - Brain angiotensin-converting enzyme type 2 shedding contributes to the
      development of neurogenic hypertension.
AB  - RATIONALE: Overactivity of the brain renin-angiotensin system is a major
      contributor to neurogenic hypertension. Although overexpression of angiotensin
      converting enzyme type 2 (ACE2) has been shown to be beneficial in reducing
      hypertension by transforming angiotensin II into angiotensin-(1-7), several
      groups have reported decreased brain ACE2 expression and activity during the
      development of hypertension. OBJECTIVE: We hypothesized that ADAM17-mediated ACE2
      shedding results in decreased membrane-bound ACE2 in the brain, thus promoting
      the development of neurogenic hypertension. METHODS AND RESULTS: To test this
      hypothesis, we used the deoxycorticosterone acetate-salt model of neurogenic
      hypertension in nontransgenic and syn-hACE2 mice overexpressing ACE2 in neurons.
      Deoxycorticosterone acetate-salt treatment in nontransgenic mice led to
      significant increases in blood pressure, hypothalamic angiotensin II levels,
      inflammation, impaired baroreflex sensitivity, and autonomic dysfunction, as well
      as decreased hypothalamic ACE2 activity and expression, although these changes
      were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2
      expression and activity in the brain paralleled an increase in ACE2 activity in
      the cerebrospinal fluid of nontransgenic mice after deoxycorticosterone acetate
      salt treatment and were accompanied by enhanced ADAM17 expression and activity in
      the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the
      development of hypertension and restored ACE2 activity and baroreflex function.
      CONCLUSIONS: Our data provide the first evidence that ADAM17-mediated shedding
      impairs brain ACE2 compensatory activity, thus contributing to the development of
      neurogenic hypertension.

PMID- 24014831
TI  - Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG
      145, in homozygous familial hypercholesterolemia.
AB  - BACKGROUND: Homozygous familial hypercholesterolemia is a rare, serious disorder
      with a substantial reduction in low-density lipoprotein (LDL) receptor function,
      severely elevated LDL cholesterol, cardiovascular disease, and often death in
      childhood. Response to conventional drug therapies is modest. Monoclonal
      antibodies to proprotein convertase subtilisin/kexin 9 (PCSK9) reduce LDL
      cholesterol in heterozygous familial hypercholesterolemia. The effect in
      homozygous familial hypercholesterolemia is unknown and uncertain. We evaluated
      the efficacy and safety of AMG 145 in an open-label, single-arm, multicenter,
      dose-scheduling pilot study in patients with homozygous familial
      hypercholesterolemia. METHODS AND RESULTS: Eight patients with LDL receptor
      negative or -defective homozygous familial hypercholesterolemia on stable drug
      therapy were treated with subcutaneous 420 mg AMG 145 every 4 weeks for >=12
      weeks, followed by 420 mg AMG 145 every 2 weeks for an additional 12 weeks. All
      patients completed both treatment periods. Mean change from baseline in LDL
      cholesterol at week 12 was -16.5% (range, 5.2% to -43.6%; P=0.0781) and -13.9%
      (range, 39.9% to -43.3%; P=0.1484) with 4- and 2-week dosing, respectively. No
      reduction was seen in the 2 receptor-negative patients. Over the treatment
      periods, mean+/-SD LDL cholesterol reductions in the 6 LDL receptor-defective
      patients were 19.3+/-16% and 26.3+/-20% with 4- and 2-week dosing, respectively
      (P=0.0313 for both values), ranging from 4% to 48% with 2-week dosing. No serious
      side effects were reported. CONCLUSION: This study demonstrates significant and
      dose-related LDL cholesterol lowering with a PCSK9 monoclonal antibody in
      homozygous familial hypercholesterolemia patients with defective LDL receptor
      activity but no reduction in those who were receptor negative.

PMID- 24014830
TI  - MicroRNA-663 regulates human vascular smooth muscle cell phenotypic switch and
      vascular neointimal formation.
AB  - RATIONALE: Abnormal phenotypic switch of vascular smooth muscle cell (VSMC) is a
      hallmark of vascular disorders such as atherosclerosis and restenosis after
      angioplasty. MicroRNAs (miRNAs) have emerged as important regulators for VSMC
      function, and we recently identified miR-663 as critical for controlling human
      aortic smooth muscle cell proliferation. OBJECTIVE: To investigate whether miR
      663 plays a role in human VSMC phenotypic switch and the development of neointima
      formation. METHODS AND RESULTS: By using quantitative reverse-transcription
      polymerase chain reaction, we found that miR-663 was significantly downregulated
      in human aortic VSMCs on platelet-derived growth factor treatment, whereas
      expression was markedly increased during VSMC differentiation. Furthermore, we
      demonstrated that overexpression of miR-663 increased expression of VSMC
      differentiation marker genes, such as smooth muscle 22alpha, smooth muscle alpha
      actin, calponin, and smooth muscle myosin heavy chain, and potently inhibited
      platelet-derived growth factor-induced VSMC proliferation and migration. We
      identified the transcription factor JunB and myosin light chain 9 as downstream
      targets of miR-663 in human VSMCs, because overexpression of miR-663 markedly
      inhibited expression of JunB and its downstream molecules, such as myosin light
      chain 9 and matrix metalloproteinase 9. Finally, we showed that adeno-miR-663
      markedly suppressed the neointimal lesion formation by ~50% in mice after
      vascular injury induced by carotid artery ligation, specifically via decreased
      JunB expression. CONCLUSIONS: These results indicate that miR-663 is a novel
      modulator of human VSMC phenotypic switch by targeting JunB/myosin light chain 9
      expression. These findings suggest that targeting miR-663 or its specific
      downstream targets in human VSMCs may represent an attractive approach for the
      treatment of proliferative vascular diseases.

PMID- 24014833
TI  - Reverse remodeling in the perspective of decision making for mitral valve repair
      with the MitraClip.

PMID- 24014832
TI  - Impaired cholesterol metabolism and enhanced atherosclerosis in clock mutant
      mice.
AB  - BACKGROUND: Clock is a key transcription factor that positively controls
      circadian regulation. However, its role in plasma cholesterol homeostasis and
      atherosclerosis has not been studied. METHODS AND RESULTS: We show for the first
      time that dominant-negative Clock mutant protein (Clock(Delta19/Delta19))
      enhances plasma cholesterol and atherosclerosis in 3 different mouse models.
      Detailed analyses revealed that Clk(Delta19/Delta19)Apoe(-/-) mice display
      hypercholesterolemia resulting from the accumulation of apolipoprotein B48
      containing cholesteryl ester-rich lipoproteins. Physiological studies showed that
      enhanced cholesterol absorption by the intestine contributes to
      hypercholesterolemia. Molecular studies indicated that the expression of Niemann
      Pick C1 Like 1, Acyl-CoA:Cholesterol acyltransferase 1, and microsomal
      triglyceride transfer protein in the intestines of Clk(Delta19/Delta19)Apoe(-/-)
      mice was high and that enterocytes assembled and secreted more chylomicrons.
      Furthermore, we identified macrophage dysfunction as another potential cause of
      increased atherosclerosis in Clk(Delta19/Delta19)Apoe(-/-) mice. Macrophages from
      Clk(Delta19/Delta19)Apoe(-/-) mice expressed higher levels of scavenger receptors
      and took up more modified lipoproteins compared with Apoe(-/-) mice, but they
      expressed low levels of ATP binding casette protein family A member 1 and were
      defective in cholesterol efflux. Molecular studies revealed that Clock regulates
      ATP binding casette protein family A member 1 expression in macrophages by
      modulating upstream transcription factor 2 expression. CONCLUSIONS:
      Clock(Delta19/Delta19) protein enhances atherosclerosis by increasing intestinal
      cholesterol absorption, augmenting uptake of modified lipoproteins by
      macrophages, and reducing cholesterol efflux from macrophages. These studies
      establish that circadian Clock activity is crucial in maintaining low plasma
      cholesterol levels and in reducing atherogenesis in mice.

PMID- 24014834
TI  - Relationship between the magnitude of reduction in mitral regurgitation severity
      and left ventricular and left atrial reverse remodeling after MitraClip therapy.
AB  - BACKGROUND: MitraClip has been shown to reduce mitral regurgitation (MR) severity
      safely but to a lesser degree than surgery. No data exist on the magnitude of MR
      reduction necessary to reverse left ventricular (LV) and left atrial (LA)
      dilation in patients with severe MR. Therefore, an analysis was performed to
      evaluate the relationship between MR reduction and LV and LA volumes after
      MitraClip therapy. METHODS AND RESULTS: A total of 801 patients treated with
      MitraClip and 80 patients treated surgically were included. All patients had
      severe (3-4+) MR. MR severity, LV volumes at end-diastole and end-systole, and LA
      volumes were measured at baseline, discharge, 30 days, 6 months, and 1 year by an
      independent echocardiographic core laboratory. A linear repeated measures model
      was developed to determine the relationship between MR severity and time of
      measurement postindex procedure on longitudinal LV and LA volumes. Separate
      models were fit for functional MR and degenerative MR. In both degenerative and
      functional MR, reduction in LV volumes at end-diastole was associated with degree
      of residual MR at 12 months (P<0.0001). LV volumes at end-systole was
      significantly reduced in functional MR but not degenerative MR. LA volumes were
      significantly related to reduction of MR severity in both groups. CONCLUSIONS:
      Reduction of LV volumes at end-diastole and LA volumes, but not LV volumes at end
      systole in degenerative MR, is consistent with correction of volume overload from
      primary MR. Reduction of all 3 measurements in functional MR demonstrates reverse
      remodeling when MR severity is reduced to either 1+ or 2+ by MitraClip therapy.
      CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00209274.

PMID- 24014835
TI  - Endothelial microparticle-mediated transfer of MicroRNA-126 promotes vascular
      endothelial cell repair via SPRED1 and is abrogated in glucose-damaged
      endothelial microparticles.
AB  - BACKGROUND: Repair of the endothelium after vascular injury is crucial for
      preserving endothelial integrity and preventing the development of vascular
      disease. The underlying mechanisms of endothelial cell repair are largely
      unknown. We sought to investigate whether endothelial microparticles (EMPs),
      released from apoptotic endothelial cells (ECs), influence EC repair. METHODS AND
      RESULTS: Systemic treatment of mice with EMPs after electric denudation of the
      endothelium accelerated reendothelialization in vivo. In vitro experiments
      revealed that EMP uptake in ECs promotes EC migration and proliferation, both
      critical steps in endothelial repair. To dissect the underlying mechanisms,
      Taqman microRNA array was performed, and microRNA (miR)-126 was identified as the
      predominantly expressed miR in EMPs. The following experiments demonstrated that
      miR-126 was transported into recipient human coronary artery endothelial cells by
      EMPs and functionally regulated the target protein sprouty-related, EVH1 domain
      containing protein 1 (SPRED1). Knockdown of miR-126 in EMPs abrogated EMP
      mediated effects on human coronary artery endothelial cell migration and
      proliferation in vitro and reendothelialization in vivo. Interestingly, after
      simulating diabetic conditions, EMPs derived from glucose-treated ECs contained
      significantly lower amounts of miR-126 and showed reduced endothelial repair
      capacity in vitro and in vivo. Finally, expression analysis of miR-126 in
      circulating microparticles from 176 patients with stable coronary artery disease
      with and without diabetes mellitus revealed a significantly reduced miR-126
      expression in circulating microparticles from diabetic patients. CONCLUSIONS:
      Endothelial microparticles promote vascular endothelial repair by delivering
      functional miR-126 into recipient cells. In pathological hyperglycemic
      conditions, EMP-mediated miR-126-induced EC repair is altered.

PMID- 24014836
TI  - Single-nucleotide polymorphisms and other mismatches reduce performance of
      quantitative PCR assays.
AB  - BACKGROUND: Genome-sequencing studies have led to an immense increase in the
      number of known single-nucleotide polymorphisms (SNPs). Designing primers that
      anneal to regions devoid of SNPs has therefore become challenging. We studied the
      impact of one or more mismatches in primer-annealing sites on different
      quantitative PCR (qPCR)-related parameters, such as quantitative cycle (Cq),
      amplification efficiency, and reproducibility. METHODS: We used synthetic
      templates and primers to assess the effect of mismatches at primer-annealing
      sites on qPCR assay performance. Reactions were performed with 5 commercially
      available master mixes. We studied the effects of the number, type, and position
      of priming mismatches on Cq value, PCR efficiency, reproducibility, and yield.
      RESULTS: The impact of mismatches was most pronounced for the number of
      mismatched nucleotides and for their distance from the 3' end of the primer. In
      addition, having >=4 mismatches in a single primer or having 3 mismatches in one
      primer and 2 in the other was required to block a reaction completely. Finally,
      the degree of the mismatch effect was concentration independent for single
      mismatches, whereas concentration independence failed at higher template
      concentrations as the number of mismatches increased. CONCLUSIONS: Single
      mismatches located >5 bp from the 3' end have a moderate effect on qPCR
      amplification and can be tolerated. This finding, together with the concentration
      independence for single mismatches and the complete blocking of the PCR reaction
      for >=4 mismatches, can help to chart mismatch behavior in qPCR reactions and
      increase the rate of successful primer design for sequences with a high SNP
      density or for homologous regions of sequence.

PMID- 24014837
TI  - First metabolic profile of XLR-11, a novel synthetic cannabinoid, obtained by
      using human hepatocytes and high-resolution mass spectrometry.
AB  - BACKGROUND: Since the mid-2000s synthetic cannabinoids have been abused as
      recreational drugs, prompting scheduling of these substances in many countries.
      To circumvent legislation, manufacturers constantly market new compounds; [1-(5
      fluoropentyl)indol-3-yl]-(2,2,3,3-tetramethylcyclopropyl)methanone (XLR-11), the
      fluorinated UR-144 analog, is one of the most recent and widely abused drugs, and
      its use is now linked with acute kidney injury. Our goal was to investigate XLR
      11 metabolism for identification of major urinary targets in analytical methods
      and to clarify the origin of metabolites when one or more parent synthetic
      cannabinoids can be the source. METHODS: We incubated 10 MUmol/L XLR-11 with
      pooled human hepatocytes and sampled after 1 and 3 h. Samples were analyzed by
      high-resolution mass spectrometry with a TOF scan followed by information
      dependent acquisition triggered product ion scans with dynamic background
      subtraction and mass defect filters. Scans were thoroughly data mined with
      different data processing algorithms (Metabolite Pilot 1.5). RESULTS: XLR-11
      underwent phase I and II metabolism, producing more than 25 metabolites resulting
      from hydroxylation, carboxylation, hemiketal and hemiacetal formation, internal
      dehydration, and further glucuronidation of some oxidative metabolites. No
      sulfate or glutathione conjugation was observed. XLR-11 also was defluorinated,
      forming UR-144 metabolites. On the basis of mass spectrometry peak areas, we
      determined that the major metabolites were 2'-carboxy-XLR-11, UR-144 pentanoic
      acid, 5-hydroxy-UR-144, hydroxy-XLR-11 glucuronides, and 2'-carboxy-UR-144
      pentanoic acid. Minor metabolites were combinations of the biotransformations
      mentioned above, often glucuronidated. CONCLUSIONS: These are the first data
      defining major urinary targets of XLR-11 metabolism that could document XLR-11
      intake in forensic and clinical investigations.

PMID- 24014840
TI  - Mental health status and gender as risk factors for onset of physical illness
      over 10 years.
AB  - BACKGROUND: There is a growing interest in understanding the connection between
      mental illness (MI) and the onset of new physical illnesses among previously
      physically healthy individuals. Yet the role of gender is often forgotten in
      research focused on comorbidity of health problems. The objective of this study
      was to examine gender differences in the onset of physical illness in a cohort of
      respondents who met criteria for MI compared with a control cohort without mental
      health problems. METHODS: This cohort study, conducted in Ontario, Canada, used a
      unique linked dataset with information from the 2000-2001 Canadian Community
      Health Survey and medical records (n=15,902). We used adjusted Cox proportional
      survival analysis to examine risk of onset of four physical health problems
      (chronic obstructive pulmonary disorder, asthma, hypertension and diabetes) for
      those with and without baseline MI across a 10-year period (2002-2011) among
      respondents aged 18-74 years. We controlled for socioeconomic and health
      indicators associated with health. RESULTS: The incidence of physical illness in
      the MI cohort was 28.5% among women and 29.9% among men (p=0.85) relative to
      controls (23.8% and 24%, respectively; p=0.48). Women in the MI cohort developed
      secondary physical health problems a year earlier than their male counterparts
      (p=0.002). Findings from the Cox proportional survival regression showed that
      women were at 14% reduced risk of developing physical illness, meaning that men
      were more disadvantaged (HR=0.89, CI 0.80 to 0.98). Those in the MI cohort were
      at 10 times greater risk of developing a secondary physical illness over the 10
      year period (HR=1.10, CI 0.98 to 1.21). There was no significant interaction
      between gender and MI cohort (HR=1.05, CI 0.85 to 1.27). CONCLUSIONS: Policy and
      clinical practice have to be sensitive to these complex-needs patients. Gender
      specific treatment and prevention practices can be developed to target those at
      higher risk of multiple health conditions.

PMID- 24014863
TI  - A receptor-like protein RMC is involved in regulation of iron acquisition in
      rice.
AB  - Iron (Fe) is one of the essential mineral elements for plant growth and
      development. Acquisition of Fe by plants is mediated by a complex network
      involving Fe mobilization, uptake by root cells, and transport within plants.
      Here, we evaluated the role of a previously clarified gene encoding a receptor
      like protein from rice, OsRMC, in the regulation of Fe acquisition by comparing
      Fe concentration, biomass, and expression patterns of genes associated with Fe
      mobilization and transport in wild-type (WT) rice with those in OsRMC
      overexpression and RNA interference (RNAi) knockdown transgenic rice plants.
      Expression of OsRMC was upregulated in both shoots and roots upon exposure of WT
      to Fe-deficient medium. Expression levels of OsRMC were positively correlated
      with Fe concentration in rice plants under both Fe-sufficient and Fe-deficient
      conditions such that overexpression and RNAi lines had higher and lower Fe
      concentration in both roots and shoots than WT plants, respectively. Moreover,
      overexpression of OsRMC conferred greater accumulation of Fe in mature seeds
      under Fe-sufficient conditions. OsRMC may also play a role in regulation of Fe
      deficiency-induced changes in root growth, as evidenced by greater and smaller
      root systems of OsRMC overexpression lines and RNAi lines than WT under Fe
      deficient conditions, respectively. Several Fe deficiency-responsive genes
      including OsDMAS1, OsNAS1, OsNAS2, OsNAAT1, OsIRT1, OsYSL15, and OsIRO2 were up-
      and downregulated in OsRMC-overexpressing and RNAi plants compared with WT rice
      plants. These novel findings highlight an important role of OsRMC played in
      mediation of Fe acquisition and root growth in rice, particularly under Fe
      deficient conditions. 

PMID- 24014865
TI  - The cellular mechanics of an invasive lifestyle.
AB  - Invasive behaviour is the hallmark of a variety of cell types of animal, plant,
      and fungal origin. Here we review the purpose and mechanism of invasive growth
      and migration. The focus is on the physical principles governing the process, the
      source of invasive force, and the cellular mechanism by which the cell penetrates
      the substrate. The current experimental methods for measuring invasive force and
      the modelling approaches for studying invasive behaviour are explained, and
      future experimental strategies are proposed. 

PMID- 24014864
TI  - A DELLA gene, RhGAI1, is a direct target of EIN3 and mediates ethylene-regulated
      rose petal cell expansion via repressing the expression of RhCesA2.
AB  - Ethylene plays an important role in organ growth. In Arabidopsis, ethylene can
      inhibit root elongation by stabilizing DELLA proteins. In previous work, it was
      found that ethylene suppressed cell expansion in rose petals, and five
      unisequences of DELLA genes are induced by ethylene. However, the mechanism of
      transcriptional regulation of DELLA genes by ethylene is still not clear. The
      results showed that the expression of RhGAI1 was induced in both ethylene-treated
      and ETR gene-silenced rose petals, and the promoter activity of RhGAI1 was
      strongly induced by RhEIN3-3 in Arabidopsis protoplasts. What is more, RhEIN3-3
      could bind to the promoter of RhGAI1 directly in an electrophoretic mobility
      shift assay (EMSA). Cell expansion was suppressed in RhGAI1-Delta17-overexpressed
      Arabidopsis petals and promoted in RhGAI1-silenced rose petals. Moreover, in
      RhGAI1-silenced petals, the expression of nine cell expansion-related genes was
      clearly changed, and RhGAI1 can bind to the promoter of RhCesA2 in an EMSA. These
      results suggested that RhGAI1 was regulated by ethylene at the transcriptional
      level, and RhGAI1 was a direct target of RhEIN3-3. Also, RhGAI1 was shown to be
      involved in cell expansion partially through regulating the expression of cell
      expansion-related genes. Furthermore, RhCesA2 was a direct target of RhGAI1. This
      work uncovers the transcriptional regulation of RhGAI1 by ethylene and provides a
      better understanding of how ethylene regulates petal expansion in roses. 

PMID- 24014867
TI  - Integrative biomechanics for tree ecology: beyond wood density and strength.
AB  - Functional ecology has long considered the support function as important, but its
      biomechanical complexity is only just being elucidated. We show here that it can
      be described on the basis of four biomechanical traits, two safety traits against
      winds and self-buckling, and two motricity traits involved in sustaining an
      upright position, tropic motion velocity (MV) and posture control (PC). All these
      traits are integrated at the tree scale, combining tree size and shape together
      with wood properties. The assumption of trait constancy has been used to derive
      allometric scaling laws, but it was more recently found that observing their
      variations among environments and functional groups, or during ontogeny, provides
      more insights into adaptive syndromes of tree shape and wood properties. However,
      oversimplified expressions have often been used, possibly concealing key adaptive
      drivers. An extreme case of oversimplification is the use of wood basic density
      as a proxy for safety. Actually, as wood density is involved in stiffness, loads,
      and construction costs, the impact of its variations on safety is non-trivial.
      Moreover, other wood features, especially the microfibril angle (MFA), are also
      involved. Furthermore, wood is not only stiff and strong, but it also acts as a
      motor for MV and PC. The relevant wood trait for this is maturation strain
      asymmetry. Maturation strains vary with cell-wall characteristics such as MFA,
      rather than with wood density. Finally, the need for further studies about the
      ecological relevance of branching patterns, motricity traits, and growth
      responses to mechanical loads is discussed. 

PMID- 24014866
TI  - The rare sugar D-allose acts as a triggering molecule of rice defence via ROS
      generation.
AB  - Only D-allose, among various rare monosaccharides tested, induced resistance to
      Xanthomonas oryzae pv. oryzae in susceptible rice leaves with defence responses:
      reactive oxygen species, lesion mimic formation, and PR-protein gene expression.
      These responses were suppressed by ascorbic acid or diphenylene iodonium.
      Transgenic rice plants overexpressing OsrbohC, encoding NADPH oxidase, were
      enhanced in sensitivity to D-allose. D-Allose-mediated defence responses were
      suppressed by the presence of a hexokinase inhibitor. 6-Deoxy-D-allose, a
      structural derivative of D-allose unable to be phosphorylated, did not confer
      resistance. Transgenic rice plants expressing Escherichia coli AlsK encoding D
      allose kinase to increase D-allose 6-phosphate synthesis were more sensitive to D
      allose, but E. coli AlsI encoding D-allose 6-phosphate isomerase expression to
      decrease D-allose 6-phosphate reduced sensitivity. A D-glucose 6-phosphate
      dehydrogenase-defective mutant was also less sensitive, and OsG6PDH1
      complementation restored full sensitivity. These results reveal that a
      monosaccharide, D-allose, induces rice resistance to X. oryzae pv. oryzae by
      activating NADPH oxidase through the activity of D-glucose 6-phosphate
      dehydrogenase, initiated by hexokinase-mediated conversion of D-allose to D
      allose 6-phosphate, and treatment with D-allose might prove to be useful for
      reducing disease development in rice.

PMID- 24014868
TI  - Modes of deformation of walled cells.
AB  - The bewildering morphological diversity found in cells is one of the starkest
      illustrations of life's ability to self-organize. Yet the morphogenetic
      mechanisms that produce the multifarious shapes of cells are still poorly
      understood. The shared similarities between the walled cells of prokaryotes, many
      protists, fungi, and plants make these groups particularly appealing to begin
      investigating how morphological diversity is generated at the cell level. In this
      review, I attempt a first classification of the different modes of surface
      deformation used by walled cells. Five modes of deformation were identified:
      inextensional bending, equi-area shear, elastic stretching, processive
      intussusception, and chemorheological growth. The two most restrictive modes
      inextensional and equi-area deformations-are embodied in the exine of pollen
      grains and the wall-like pellicle of euglenoids, respectively. For these modes,
      it is possible to express the deformed geometry of the cell explicitly in terms
      of the undeformed geometry and other easily observable geometrical parameters.
      The greatest morphogenetic power is reached with the processive intussusception
      and chemorheological growth mechanisms that underlie the expansive growth of
      walled cells. A comparison of these two growth mechanisms suggests a possible way
      to tackle the complexity behind wall growth. 

PMID- 24014869
TI  - Peptides as triggers of plant defence.
AB  - Plants are confronted with several biotic stresses such as microbial pathogens
      and other herbivores. To defend against such attackers, plants possess an array
      of pattern recognition receptors (PRRs) that sense the danger and consequently
      initiate a defence programme that prevents further damage and spreading of the
      pest. Characteristic pathogenic structures, so-called microbe-associated
      molecular patterns (MAMPs), serve as signals that allow the plant to sense
      invaders. Additionally, pathogens wound or damage the plant and the resulting
      release of damage-associated molecular patterns (DAMPs) serves as a warning
      signal. This review focuses on peptides that serve as triggers or amplifiers of
      plant defence and thus follow the definition of a MAMP or a DAMP. 

PMID- 24014870
TI  - Message in a bottle: small signalling peptide outputs during growth and
      development.
AB  - Classical and recently found phytohormones play an important role in plant growth
      and development, but plants additionally control these processes through small
      signalling peptides. Over 1000 potential small signalling peptide sequences are
      present in the Arabidopsis genome. However, to date, a mere handful of small
      signalling peptides have been functionally characterized and few have been linked
      to a receptor. Here, we assess the potential small signalling peptide outputs,
      namely the molecular, biochemical, and morphological changes they trigger in
      Arabidopsis. However, we also include some notable studies in other plant
      species, in order to illustrate the varied effects that can be induced by small
      signalling peptides. In addition, we touch on some evolutionary aspects of small
      signalling peptides, as studying their signalling outputs in single-cell green
      algae and early land plants will assist in our understanding of more complex land
      plants. Our overview illustrates the growing interest in the small signalling
      peptide research area and its importance in deepening our understanding of plant
      growth and development. 

PMID- 24014871
TI  - Arabidopsis GLASSY HAIR genes promote trichome papillae development.
AB  - Specialized plant cells form cell walls with distinct composition and properties
      pertinent to their function. Leaf trichomes in Arabidopsis form thick cell walls
      that support the upright growth of these large cells and, curiously, have strong
      light-reflective properties. To understand the process of trichome cell-wall
      maturation and the molecular origins of this optical property, mutants affected
      in trichome light reflection were isolated and characterized. It was found that
      GLASSY HAIR (GLH) genes are required for the formation of surface papillae
      structures at late stages of trichome development. Trichomes in these mutants
      appeared transparent due to unobstructed light transmission. Genetic analysis of
      the isolated mutants revealed seven different gene loci. Two--TRICHOME
      BIREFRINGENCE (TBR) and NOK (Noeck)--have been reported previously to have the
      glassy trichome mutant phenotype. The other five glh mutants were analysed for
      cell-wall-related phenotypes. A significant reduction was found in cellulose
      content in glh2 and glh4 mutant trichomes. In addition to the glassy trichome
      phenotype, the glh6 mutants showed defects in leaf cuticular wax, and glh6 was
      found to represent a new allele of the eceriferum 10 (cer10) mutation. Trichomes
      of the glh1 and glh3 mutants did not show any other phenotypes beside reduced
      papillae formation. These data suggest that the GLH1 and GLH3 genes may have
      specific functions in trichome papillae formation, whereas GLH2, GLH4, and GLH6
      genes are also involved in deposition of other cell-wall components.

PMID- 24014872
TI  - Comparative proteomic and transcriptomic approaches to address the active role of
      GA4 in Japanese apricot flower bud dormancy release.
AB  - Hormones are closely associated with dormancy in deciduous fruit trees, and
      gibberellins (GAs) are known to be particularly important. In this study, we
      observed that GA4 treatment led to earlier bud break in Japanese apricot. To
      understand better the promoting effect of GA4 on the dormancy release of Japanese
      apricot flower buds, proteomic and transcriptomic approaches were used to analyse
      the mechanisms of dormancy release following GA4 treatment, based on two
      dimensional gel electrophoresis (2-DE) and digital gene expression (DGE)
      profiling, respectively. More than 600 highly reproducible protein spots (P<0.05)
      were detected and, following GA4 treatment, 38 protein spots showed more than a 2
      fold difference in expression, and 32 protein spots were confidently identified
      according to the databases. Compared with water treatment, many proteins that
      were associated with energy metabolism and oxidation-reduction showed significant
      changes after GA4 treatment, which might promote dormancy release. We observed
      that genes at the mRNA level associated with energy metabolism and oxidation
      reduction also played an important role in this process. Analysis of the
      functions of the identified proteins and genes and the related metabolic pathways
      would provide a comprehensive proteomic and transcriptomic view of the
      coordination of dormancy release after GA4 treatment in Japanese apricot flower
      buds. 

PMID- 24014873
TI  - Heterosis, stress, and the environment: a possible road map towards the general
      improvement of crop yield.
AB  - Contemporary plant breeding is under pressure to improve crop productivity at a
      rate surpassing past achievements. Different research groups dealing with this
      issue reached similar conclusions that the solution lies in improved biomass
      production by way of enhanced light capture and use efficiency, modified
      photosystem biochemistry, and improved partitioning of assimilates to the
      economic part of the plant. There seems to be a consensus of sorts. This 'opinion
      paper' calls attention to the phenomenon of heterosis, as expressed in maize,
      sorghum, and other crops where, depending on the case and the trait, larger
      biomass and greater yield have been achieved without a change in growth duration,
      photosystem biochemistry, or harvest index. This discussion maintains that there
      is no consensus about the genetics or the genomics of heterosis in regulating
      yield under diverse environments. Therefore, in a search for the basis of
      heterosis in yield and adaptation, the discussion bypasses the genetics and
      searches for answers in the phenomics of heterosis. The heterotic phenotype in
      itself provides challenging and important hints towards improving the yield of
      open-pollinated crops in general. These hints are linked to the homeostasis of
      photosynthesis with respect to temperature, the photobiology of the plant as
      mediated by phytochrome, the architectural foundations of the formation of a
      large sink, and the associated hormones and signals in controlling sink
      differentiation and source-sink communication. This discussion does not lay out
      plans and protocols but provides clues to explore within and beyond the current
      thinking about breeding for high yield. 

PMID- 24014874
TI  - Genome-wide identification and characterization of cadmium-responsive microRNAs
      and their target genes in radish (Raphanus sativus L.) roots.
AB  - MicroRNAs (miRNAs) are endogenous non-coding small RNAs that play vital
      regulatory roles in plant growth, development, and environmental stress
      responses. Cadmium (Cd) is a non-essential heavy metal that is highly toxic to
      living organisms. To date, a number of conserved and non-conserved miRNAs have
      been identified to be involved in response to Cd stress in some plant species.
      However, the miRNA-mediated gene regulatory networks responsive to Cd stress in
      radish (Raphanus sativus L.) remain largely unexplored. To dissect Cd-responsive
      miRNAs and their targets systematically at the global level, two small RNA
      libraries were constructed from Cd-treated and Cd-free roots of radish seedlings.
      Using Solexa sequencing technology, 93 conserved and 16 non-conserved miRNAs
      (representing 26 miRNA families) and 28 novel miRNAs (representing 22 miRNA
      families) were identified. In all, 15 known and eight novel miRNA families were
      significantly differently regulated under Cd stress. The expression patterns of a
      set of Cd-responsive miRNAs were validated by quantitative real-time PCR. Based
      on the radish mRNA transcriptome, 18 and 71 targets for novel and known miRNA
      families, respectively, were identified by the degradome sequencing approach.
      Furthermore, a few target transcripts including phytochelatin synthase 1 (PCS1),
      iron transporter protein, and ABC transporter protein were involved in plant
      response to Cd stress. This study represents the first transcriptome-based
      analysis of miRNAs and their targets responsive to Cd stress in radish roots.
      These findings could provide valuable information for functional characterization
      of miRNAs and their targets in regulatory networks responsive to Cd stress in
      radish. 

PMID- 24014876
TI  - IFIT2 is an effector protein of type I IFN-mediated amplification of
      lipopolysaccharide (LPS)-induced TNF-alpha secretion and LPS-induced endotoxin
      shock.
AB  - Type I IFN signaling amplifies the secretion of LPS-induced proinflammatory
      cytokines such as TNF-alpha or IL-6 and might thus contribute to the high
      mortality associated with Gram-negative septic shock in humans. The underlying
      molecular mechanism, however, is ill defined. In this study, we report the
      generation of mice deficient in IFN-induced protein with tetratricopeptide
      repeats 2 (Ifit2) and demonstrate that Ifit2 is a critical signaling intermediate
      for LPS-induced septic shock. Ifit2 expression was significantly upregulated in
      response to LPS challenge in an IFN-alpha receptor- and IFN regulatory factor
      (Irf)9-dependent manner. Also, LPS induced secretion of IL-6 and TNF-alpha by
      bone marrow-derived macrophages (BMDMs) was significantly enhanced in the
      presence of Ifit2. In accordance, Ifit2-deficient mice exhibited significantly
      reduced serum levels of IL-6 and TNF-alpha and reduced mortality in an endotoxin
      shock model. Investigation of the underlying signal transduction events revealed
      that Ifit2 upregulates Irf3 phosphorylation. In the absence of Irf3, reduced Ifn
      beta mRNA expression and Ifit2 protein expression after LPS stimulation was
      found. Also, Tnf-alpha and Il-6 secretion but not Tnf-alpha and Il-6 mRNA
      expression levels were reduced. Thus, IFN-stimulated Ifit2 via enhanced Irf3
      phosphorylation upregulates the secretion of proinflammatory cytokines. It
      thereby amplifies LPS-induced cytokine production and critically influences the
      outcome of endotoxin shock. 

PMID- 24014875
TI  - Fibrosis and subsequent cytopenias are associated with basic fibroblast growth
      factor-deficient pluripotent mesenchymal stromal cells in large granular
      lymphocyte leukemia.
AB  - Cytopenias occur frequently in systemic lupus erythematosus, rheumatoid
      arthritis, Felty's syndrome, and large granular lymphocyte (LGL) leukemia, but
      the bone marrow microenvironment has not been systematically studied. In LGL
      leukemia (n = 24), retrospective analysis of bone marrow (BM) histopathology
      revealed severe fibrosis in 15 of 24 patients (63%) in association with the
      presence of cytopenias, occurrence of autoimmune diseases, and splenomegaly, but
      was undetectable in control cases with B cell malignancies (n = 11). Fibrosis
      severity correlated with T cell LGL cell numbers in the BM, but not in the
      periphery, suggesting deregulation is limited to the BM microenvironment. To
      identify fibrosis-initiating populations, primary mesenchymal stromal cultures
      (MSCs) from patients were characterized and found to display proliferation
      kinetics and overabundant collagen deposition, but displayed normal telomere
      lengths and osteoblastogenic, chondrogenic, and adipogenic differentiation
      potentials. To determine the effect of fibrosis on healthy hematopoietic
      progenitor cells (HPCs), bioartificial matrixes from rat tail or purified human
      collagen were found to suppress HPC differentiation and proliferation. The
      ability of patient MSCs to support healthy HSC proliferation was significantly
      impaired, but could be rescued with collagenase pretreatment. Clustering analysis
      confirmed the undifferentiated state of patient MSCs, and pathway analysis
      revealed an inverse relationship between cell division and profibrotic ontologies
      associated with reduced basic fibroblast growth factor production, which was
      confirmed by ELISA. Reconstitution with exogenous basic fibroblast growth factor
      normalized patient MSC proliferation, collagen deposition, and HPC supportive
      function, suggesting LGL BM infiltration and secondary accumulation of MSC
      derived collagen is responsible for hematopoietic failure in autoimmune
      associated cytopenias in LGL leukemia. 

PMID- 24014877
TI  - Antibodies targeting human OX40 expand effector T cells and block inducible and
      natural regulatory T cell function.
AB  - Current cancer vaccines induce tumor-specific T cell responses without sustained
      tumor regression because immunosuppressive elements within the tumor induce
      exhaustion of effector T cells and infiltration of immune-suppressive regulatory
      T cells (Tregs). Therefore, much effort has been made to generate agonistic Abs
      targeting members of the TNFR superfamily, such as OX40, 4-1BB, and GITR,
      expressed on effector T cells and Tregs, to reinvigorate T cell effector function
      and block Treg-suppressive function. In this article, we describe the development
      of a panel of anti-human OX40 agonistic mouse mAbs that could promote effector
      CD4(+) and CD8(+) T cell proliferation, inhibit the induction of CD4(+) IL-10 
      producing type 1 regulatory T cells, inhibit the expansion of ICOS(+)IL-10(+)
      Tregs, inhibit TGF-beta-induced FOXP3 expression on naive CD4(+) T cells, and
      block natural Treg-suppressive function. We humanized two anti-human OX40 mAb
      clones, and they retained the potency of their parental clones. These Abs should
      provide broad opportunities for potential combination therapy to treat a wide
      realm of cancers and preventative vaccines against infectious diseases. 

PMID- 24014878
TI  - Distinction and temporal stability of conformational epitopes on myelin
      oligodendrocyte glycoprotein recognized by patients with different inflammatory
      central nervous system diseases.
AB  - Autoantibodies targeting conformationally intact myelin oligodendrocyte
      glycoprotein (MOG) are found in different inflammatory diseases of the CNS, but
      their antigenic epitopes have not been mapped. We expressed mutants of MOG on
      human HeLa cells and analyzed sera from 111 patients (104 children, 7 adults) who
      recognized cell-bound human MOG, but had different diseases, including acute
      disseminated encephalomyelitis (ADEM), one episode of transverse myelitis or
      optic neuritis, multiple sclerosis (MS), anti-aquaporin-4 (AQP4)-negative
      neuromyelitis optica (NMO), and chronic relapsing inflammatory optic neuritis
      (CRION). We obtained insight into the recognition of epitopes in 98 patients. All
      epitopes identified were located at loops connecting the beta strands of MOG. The
      most frequently recognized MOG epitope was revealed by the P42S mutation
      positioned in the CC'-loop. Overall, we distinguished seven epitope patterns,
      including the one mainly recognized by mouse mAbs. In half of the patients, the
      anti-MOG response was directed to a single epitope. The epitope specificity was
      not linked to certain disease entities. Longitudinal analysis of 11 patients for
      up to 5 y indicated constant epitope recognition without evidence for
      intramolecular epitope spreading. Patients who rapidly lost their anti-MOG IgG
      still generated a long-lasting IgG response to vaccines, indicating that their
      loss of anti-MOG reactivity did not reflect a general lack of capacity for long
      standing IgG responses. The majority of human anti-MOG Abs did not recognize
      rodent MOG, which has implications for animal studies. Our findings might assist
      in future detection of potential mimotopes and pave the way to Ag-specific
      depletion. 

PMID- 24014879
TI  - Induction of complement C3a receptor responses by kallikrein-related peptidase
      14.
AB  - Activation of the complement system is primarily initiated by pathogen- and
      damage-associated molecular patterns on cellular surfaces. However, there is
      increasing evidence for direct activation of individual complement components by
      extrinsic proteinases as part of an intricate crosstalk between physiological
      effector systems. We hypothesized that kallikrein-related peptidases (KLKs),
      previously known to regulate inflammation via proteinase-activated receptors, can
      also play a substantial role in innate immune responses via complement. Indeed,
      KLKs exemplified by KLK14 were efficiently able to cleave C3, the point of
      convergence of the complement cascade, indicating a potential modulation of C3
      mediated functions. By using in vitro fragmentation assays, mass spectrometric
      analysis, and cell signaling measurements, we pinpointed the generation of the
      C3a fragment of C3 as a product with potential biological activity released by
      the proteolytic action of KLK14. Using mice with various complement deficiencies,
      we demonstrated that the intraplantar administration of KLK14 results in C3
      associated paw edema. The edema response was dependent on the presence of the
      receptor for C3a but was not associated with the receptor for the downstream
      complement effector C5a. Our findings point to C3 as one of the potential
      substrates of KLKs during inflammation. Given the wide distribution of the KLKs
      in tissues and biological fluids where complement components may also be
      expressed, we suggest that via C3 processing, tissue-localized KLKs can play an
      extrinsic complement-related role during activation of the innate immune
      response. 

PMID- 24014880
TI  - Processes of sterile inflammation.
AB  - Sterile inflammation occurs in acute conditions, such as ischemia reperfusion
      injury and crystal-induced arthritis, as well as with chronic diseases, such as
      particle-induced lung diseases and atherosclerosis. The triggers of sterile
      inflammation are still being identified, and the pathways that transduce sterile
      inflammatory signals are not completely clear. Most of the innate immune pathways
      that sense infection have been implicated in sterile inflammation, although
      distinct signaling pathways of sterile inflammation exist. Whether immune
      pathology ensues after sterile inflammation depends on the balance of induced
      inflammatory and resolution pathways. Further identification of the molecular
      mechanisms of sterile inflammation will lead to novel therapeutics to treat a
      range of diseases. 

PMID- 24014881
TI  - Poly(I:C)-induced protection of neonatal mice against intestinal Cryptosporidium
      parvum infection requires an additional TLR5 signal provided by the gut flora.
AB  - The neonatal intestinal immune system is still undergoing development at birth,
      leading to a higher susceptibility to mucosal infections. In this study, we
      investigated the effect of poly(I:C) on controlling enteric infection by the
      protozoan Cryptosporidium parvum in neonatal mice. After poly(I:C)
      administration, a rapid reduction in parasite burden was observed and proved to
      be dependent on CD11c(+) cells and TLR3/TRIF signaling. Protection against C.
      parvum required additional signals provided by the gut flora through TLR5 and
      MyD88 signaling. This cooperation gave rise to higher levels of expression of
      critical mutually dependent cytokines such as interleukin 12p40 and type 1 and
      type 2 interferons, the last 2 being known to play a key role in the elimination
      of infected enterocytes. Our findings demonstrate in neonatal mice how gut flora
      synergizes with poly(I:C) to elicit protective intestinal immunity against an
      intracellular pathogen. 

PMID- 24014883
TI  - New challenges and inspired answers for anticancer drug discovery and
      development.
AB  - Many pharmaceutical companies worldwide specialize in oncology drug development
      and marketing. Among them, we have continued to take up the challenge of
      understanding the metabolism of pyrimidines as essential components of
      deoxyribonucleic acid for many years, and have provided unique products such as
      UFT((r)) and TS-1 for cancer patients. Using our cumulative experience and
      knowledge, we are currently developing novel agents such as TAS-114, a dual
      inhibitor of deoxyuridine triphosphatase and dihydropyrimidine dehydrogenase, and
      TAS-102, a unique pyrimidine derivative inducing deoxyribonucleic acid
      dysfunction in cancer cells. Regarding molecular-targeted drugs, we have made
      huge efforts to establish ideal drug discovery platforms for the last several
      years. For kinase inhibitors, we established three core platforms such as a
      kinase-directed chemical library, a kinase assay panel and a target selection
      informatics system. The core platforms were further combined with peripheral
      technologies to measure essential parameters such as physicochemical properties,
      pharmacokinetics, efficacy and toxicities. Unique drug candidates have been
      identified at an early stage by assessing all important parameters. Several
      promising programs are proceeding simultaneously in the clinical or preclinical
      development stage such as TAS-115, a dual inhibitor of c-Met and vascular
      endothelial growth factor receptor, TAS-2104, a selective Aurora A inhibitor, TAS
      117, an allosteric Akt inhibitor, TAS-2985, an irreversible fibroblast growth
      factor receptor inhibitor and TAS-2913, a T790M mutant selective epidermal growth
      factor receptor inhibitor. Other than kinase inhibitors, another drug discovery
      engine was established based on the fragment-based drug discovery technology. TAS
      116, a new class of Hsp-90alpha/beta inhibitor, is one of the products. Taiho's
      final goal is to provide innovative anticancer drugs together with companion
      diagnostics that are truly beneficial for patients.

PMID- 24014882
TI  - Prevalence of and risk factors for oral human papillomavirus among young women in
      Costa Rica.
AB  - BACKGROUND: Little is known about the epidemiology of oral human papillomavirus
      (HPV) in Latin America. METHODS: Women (N = 5838) aged 22-29 in the control and
      vaccine arms of an HPV-16/18 vaccine trial in Costa Rica had oral, cervical, and
      anal specimens collected. Samples were tested for alpha mucosal HPV types
      (SPF10/LiPA25 version 1); a subset of oral samples (n = 500) was tested for
      cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu. RESULTS: In the
      control arm (n = 2926), 1.9% of women had an oral alpha mucosal HPV detected,
      1.3% had carcinogenic HPV, and 0.4% had HPV-16; similar patterns for non-16/18
      HPV types were observed in the vaccine arm. Independent risk factors for any oral
      alpha mucosal HPV among women in the control arm included marital status
      (adjusted odds ratio [AOR], 3.2; 95% confidence interval [CI], 1.8-5.7 for single
      compared to married/living as married), number of sexual partners (AOR, 2.4; 95%
      CI, 1.0-6.1 for >=4 partners compared to 0-1 partners), chronic sinusitis (AOR,
      3.1; 95% CI, 1.5-6.7), and cervical HPV infection (AOR, 2.6; 95% CI, 1.4-4.6).
      Detection of beta HPV was common (18.6%) and not associated with sexual activity.
      CONCLUSIONS: Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in
      the oral region and were predominately associated with sexual behavior. Clinical
      Trials Registration. NCT00128661.

PMID- 24014884
TI  - Randomized Phase III study of 5-fluorouracil continuous infusion vs. sequential
      methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with
      peritoneal metastasis (JCOG0106).
AB  - OBJECTIVE: Owing to the risks of serious and sustained toxicity, anticancer drugs
      such as cisplatin and irinotecan cannot be readily administered to patients with
      gastric cancer and severe peritoneal metastasis. Therefore, a standard
      chemotherapy regimen has yet to be established for these types of patients. This
      randomized study investigated the utility of sequential methotrexate and 5
      fluorouracil therapy vs. 5-fluorouracil continuous infusion for gastric cancer
      with peritoneal metastasis. METHODS: Eligible patients had radiologically
      confirmed peritoneal metastasis with intestinal stenosis, peritoneal tumor or
      ascites. Treatment with 5-fluorouracil continuous infusion (800 mg/m(2)/day, ci,
      d1-5, q4w) or methotrexate and 5-fluorouracil therapy (methotrexate, 100 mg/m(2),
      bolus infusion, followed 3 h later by 5-fluorouracil, 600 mg/m(2), bolus
      infusion, with leucovorin rescue, q1w) was continued until disease progression or
      unacceptable toxicity. The projected sample size was 236, providing 80% power to
      detect a 40% increase in median overall survival in methotrexate and 5
      fluorouracil therapy with a one-sided alpha of 0.05. RESULTS: All 237 randomized
      patients were included in the primary analysis. The methotrexate and 5
      fluorouracil therapy arm was not superior to the 5-fluorouracil continuous
      infusion arm (median survival time, 9.4 months in the 5-fluorouracil continuous
      infusion arm, 10.6 months in the methotrexate and 5-fluorouracil therapy arm;
      hazard ratio, 0.94; 95% confidence interval, 0.72-1.22; one-sided P = 0.31).
      Frequencies of Grade 3 or higher neutropenia, Grade 3 or higher anorexia and
      treatment-related deaths were 0.9, 27.4 and 1.7%, respectively, in the 5
      fluorouracil continuous infusion arm, and 31.9, 33.6 and 0.9%, respectively, in
      the methotrexate and 5-fluorouracil therapy arm. CONCLUSIONS: Methotrexate and 5
      fluorouracil therapy is not suitable for use as standard therapy for advanced
      gastric cancer with peritoneal metastasis.

PMID- 24014885
TI  - Descriptive epidemiology of bile duct carcinoma in Osaka.
AB  - OBJECTIVE: An outbreak of bile duct carcinoma has been reported among workers in
      a certain printing company in Osaka, Japan, where there was no descriptive
      epidemiological study. We conducted descriptive studies of bile duct carcinoma in
      Osaka. METHODS: Based on the data from the Osaka Cancer Registry, the incidence
      and survival rate of intrahepatic and extrahepatic bile duct carcinomas,
      gallbladder carcinomas and hepatocellular carcinomas were analyzed. The study
      period was between 1975 and 2007, and total 108 407 incidents were retrieved from
      the Osaka Cancer Registry. Age- and sex-specific incidence rates and age
      standardized incidence rates were calculated. Standardized incidence ratios were
      evaluated for each municipality in Osaka prefecture. Relative 5-year survival
      rates were also calculated for the cases diagnosed between 1993 and 2005.
      RESULTS: Age-standardized incidence rates of bile duct carcinomas increased
      distinctly from the middle of the 1970s to the early 1980s in males and the 1990s
      in females. However, no distinct increase in the incidence rates was observed in
      2000. Standardized incidence ratios of those did not exceed the unity
      significantly in males between 1992 and 2007. In females, standardized incidence
      ratios exceeded the unity significantly in a few regions without any relation to
      the location of the printing company where the outbreak was reported. The
      relative 5-year survival rate is generally poor; however, patients who were
      diagnosed with localized disease at the age of 25-49 years showed a better
      survival. CONCLUSION: Neither change in trend nor regional accumulation of bile
      duct carcinoma was confirmed in Osaka, corresponding to the outbreak reported in
      the printing company.

PMID- 24014886
TI  - Chemically induced pluripotent stem cells (CiPSCs): a transgene-free approach.
AB  - Induced pluripotent stem cells (iPSCs) could be generated by a single gene Oct4
      and chemical compounds, in which exogenous expression of Oct4 was indispensable
      for reprogramming. Recent advances in chemical-mediated cellular reprogramming
      suggest that small molecules alone (i.e. without Yamanaka factors) can
      successfully establish iPSCs from mouse somatic cells. 

PMID- 24014888
TI  - Aggregating Local Preferences to Guide Marginal Policy Adjustments.

PMID- 24014889
TI  - Transition-Path Theory Calculations on Non-Uniform Meshes in Two and Three
      Dimensions using Finite Elements.
AB  - Rare events between states in complex systems are fundamental in many scientific
      fields and can be studied by building reaction pathways. A theoretical framework
      to analyze reaction pathways is provided by transition-path theory (TPT). The
      central object in TPT is the committor function, which is found by solution of
      the backward-Kolmogorov equation on a given potential. Once determined, the
      committor can be used to calculate reactive fluxes and rates, among other
      important quantities. We demonstrate here that the committor can be calculated
      using the method of finite elements on non-uniform meshes. We show that this
      approach makes it feasible to perform TPT calculations on 3D potentials because
      it requires many fewer degrees of freedom than a regular-mesh finite-difference
      approach. In various illustrative 2D and 3D problems, we calculate the committor
      function and reaction rates at different temperatures, and we discuss effects of
      temperatures and simple entropic barriers on the structure of the committor and
      the reaction rate constants.

PMID- 24014887
TI  - E2F1 promotes angiogenesis through the VEGF-C/VEGFR-3 axis in a feedback loop for
      cooperative induction of PDGF-B.
AB  - Angiogenesis is essential for primary tumor growth and metastatic dissemination.
      E2F1, frequently upregulated in advanced cancers, was recently shown to drive
      malignant progression. In an attempt to decipher the molecular events underlying
      this behavior, we demonstrate that the tumor cell-associated vascular endothelial
      growth factor-C/receptor-3 (VEGF-C/VEGFR-3) axis is controlled by E2F1.
      Activation or forced expression of E2F1 in cancer cells leads to the upregulation
      of VEGFR-3 and its ligand VEGF-C, whereas E2F1 depletion prevents their
      expression. E2F1-dependent receptor induction is crucial for tumor cells to
      enhance formation of capillary tubes and neovascularization in mice. We further
      provide evidence for a positive feedback loop between E2F1 and VEGFR-3 signaling
      to stimulate pro-angiogenic platelet-derived growth factor B (PDGF-B). E2F1 or
      VEGFR-3 knockdown results in reduced PDGF-B levels, while the coexpression
      synergistically upregulates promoter activity and endogenous protein expression
      of PDGF-B. Our findings delineate an as yet unrecognized function of E2F1 as
      enhancer of angiogenesis via regulation of VEGF-C/VEGFR-3 signaling in tumors to
      cooperatively activate PDGF-B expression. Targeting this pathway might be
      reasonable to complement standard anti-angiogenic treatment of cancers with
      deregulated E2F1. 

PMID- 24014890
TI  - Rehabilitation in the Punitive Era: The Gap between Rhetoric and Reality in U.S.
      Prison Programs.
AB  - Scholars of mass incarceration point to the 1970s as a pivotal turning point in
      U.S. penal history, marked by a shift towards more punitive policies and a
      consensus that "nothing works" in rehabilitating inmates. However, while there
      has been extensive research on changes in policy-makers' rhetoric, sentencing
      policy, and incarceration rates, we know very little about changes in the actual
      practices of punishment and prisoner rehabilitation. Using nationally
      representative data for U.S. state prisons, this article demonstrates that there
      were no major changes in investments in specialized facilities, funding for
      inmate services-related staff, or program participation rates throughout the late
      1970s and the 1980s. Not until the 1990s, more than a decade after the start of
      the punitive era, do we see patterns of inmate services change, as investments in
      programming switch from academic to reentry-related programs. These findings
      suggest that there is a large gap between rhetoric and reality in the case of
      inmate services and that since the 1990s, inmate "rehabilitation" has
      increasingly become equated with reentry-related life skills programs.

PMID- 24014891
TI  - Evaluating Joint Effects of Induction-Salvage Treatment Regimes on Overall
      Survival in Acute Leukemia.
AB  - Typical oncology practice often includes not only an initial, frontline
      treatment, but also subsequent treatments given if the initial treatment fails.
      The physician chooses a treatment at each stage based on the patient's baseline
      covariates and history of previous treatments and outcomes. Such sequentially
      adaptive medical decision-making processes are known as dynamic treatment
      regimes, treatment policies, or multi-stage adaptive treatment strategies.
      Conventional analyses in terms of frontline treatments that ignore subsequent
      treatments may be misleading, because they actually are an evaluation of more
      than front-line treatment effects on outcome. We are motivated by data from a
      randomized trial of four combination chemotherapies given as frontline treatments
      to patients with acute leukemia. Most patients in the trial also received a
      second-line treatment, chosen adaptively and subjectively rather than by
      randomization, either because the initial treatment was ineffective or the
      patient's cancer later recurred. We evaluate effects on overall survival time of
      the 16 two-stage strategies that actually were used. Our methods include a
      likelihood-based regression approach in which the transition times of all
      possible multi-stage outcome paths are modeled, and estimating equations with
      inverse probability of treatment weighting to correct for bias. While the two
      approaches give different numerical estimates of mean survival time, they lead to
      the same substantive conclusions when comparing the two-stage regimes.

PMID- 24014893
TI  - Cyanovanadate(III) complexes as novel additives for efficient generation of
      volatile cadmium species in complex samples prior to determinations by
      inductively coupled plasma mass spectrometry (ICP-MS).
AB  - A new method has been described for generation of volatile species of Cd using
      vanadium(III) cyanide complex. Aqueous solutions of 0.04 mol L(-1) vanadium
      chloride (VCl3) and 0.12 mol L(-1) potassium cyanide (KCN) were reacted on-line
      yielding a suspension of vanadium hydroxide, V(OH)3. This suspension was
      dissolved along the stream of sample solution in dilute HCl to form
      heptacyanovanadate(III) complex, [V(CN)7]4-. Volatile Cd species were generated
      by reacting the stream of sample solution and cyanovanadate(III) complex with
      sodium borohydride (NaBH4). Feasibility of off-line and on-online approaches was
      investigated for quantitative determinations. Better precision and daily
      stability were achieved with on-line settings. Optimum signals were obtained from
      sample solutions within a range of 3 to 5% v/v HCl. A concentration of 2% m/v
      NaBH4 was adequate to achieve an enhancement of 20-fold in the presence of
      cyanovanadate(III) complex. The limits of detection were 5.0 and 4.5 ng L(-1) for
      110Cd and 111Cd isotopes, respectively. Precision (%RSD) was better than 4.7% for
      six replicate measurements. The interferences of Cu(II) and Ni(II) were marginal
      (<10%) at 1.0 ug mL(-1). Depressive effects from Bi, Se and Sn were not
      significant below 0.1 ug mL(-1). The method was validated by determination of Cd
      using ICP-MS in certified reference materials of Nearshore seawater (CASS-4),
      Bone ash (SRM 1400), Dogfish liver (DOLT-4) and Mussel tissue (SRM 2976).

PMID- 24014894
TI  - Regiospecific oxidation of polycyclic aromatic phenols to quinones by hypervalent
      iodine reagents.
AB  - The hypervalent iodine reagents o-iodoxybenzoic acid (IBX) and bis(trifluoro
      acetoxy)iodobenzene (BTI) are shown to be general reagents for regio-controlled
      oxidation of polycyclic aromatic phenols (PAPs) to specific isomers (ortho, para,
      or remote) of polycyclic aromatic quinones (PAQs). The oxidations of a series of
      PAPs with IBX take place under mild conditions to furnish the corresponding ortho
      PAQs. In contrast, oxidations of the same series of PAPs with BTI exhibit
      variable regiospecificity, affording para-PAQs where structurally feasible and
      ortho-PAQs or remote PAQ isomers in other cases. The structures of the specific
      PAQ isomers formed are predictable on the basis of the inherent
      regioselectivities of the hypervalent iodine reagents in combination with the
      structural requirements of the phenol precursors. IBX and BTI are recommended as
      the preferred reagents for regio-controlled oxidation of PAPs to PAQs.

PMID- 24014895
TI  - Bifunctional cinchona alkaloid-squaramide-catalyzed highly enantioselective aza
      Michael addition of indolines to alpha,beta-unsaturated ketones.
AB  - An enantioselective aza-Michael addition of indolines to alpha,beta-unsaturated
      ketones was achieved using a bifunctional cinchona alkaloid-derived chiral
      squaramide derivative. Various beta-indolinyl ketone derivatives were obtained in
      good to excellent yields and with high enantioselectivity. DDQ or MnO2 oxidation
      of indoline derivatives provided convenient access to various enantioenriched N
      substituted indole derivatives.

PMID- 24014896
TI  - Family Structure and Adolescent Alcohol Use Problems: Extending Popular
      Explanations to American Indians.
AB  - Competing explanations of the relationship between family structure and alcohol
      use problems are examined using a sample of American Indian adolescents from the
      National Longitudinal Study of Adolescent Health. Living in a single-parent
      family is found to be a marker for the unequal distribution of stress exposure
      and parental alcohol use, but the effects of other family structures like non
      parent families and the presence of under 21-year-old extended family or non
      family members emerge or remain as risk or protective factors for alcohol use
      problems after a consideration of SES, family processes, peer socialization, and
      social stress. In particular, a non-parent family structure that has not been
      considered in prior research emerged as a protective family structure for
      American Indian adolescent alcohol use problems.

PMID- 24014897
TI  - Redisposition of phoma-like anamorphs in Pleosporales.
AB  - The anamorphic genus Phoma was subdivided into nine sections based on
      morphological characters, and included teleomorphs in Didymella, Leptosphaeria,
      Pleospora and Mycosphaerella, suggesting the polyphyly of the genus. Recent
      molecular, phylogenetic studies led to the conclusion that Phoma should be
      restricted to Didymellaceae. The present study focuses on the taxonomy of
      excluded Phoma species, currently classified in Phoma sections Plenodomus,
      Heterospora and Pilosa. Species of Leptosphaeria and Phoma section Plenodomus are
      reclassified in Plenodomus, Subplenodomus gen. nov., Leptosphaeria and
      Paraleptosphaeria gen. nov., based on the phylogeny determined by analysis of
      sequence data of the large subunit 28S nrDNA (LSU) and Internal Transcribed
      Spacer regions 1 & 2 and 5.8S nrDNA (ITS). Phoma heteromorphospora, type species
      of Phoma section Heterospora, and its allied species Phoma dimorphospora, are
      transferred to the genus Heterospora stat. nov. The Phoma acuta complex
      (teleomorph Leptosphaeria doliolum), is revised based on a multilocus sequence
      analysis of the LSU, ITS, small subunit 18S nrDNA (SSU), beta-tubulin (TUB), and
      chitin synthase 1 (CHS-1) regions. Species of Phoma section Pilosa and allied
      Ascochyta species were determined to belong to Pleosporaceae based on analysis of
      actin (ACT) sequence data. Anamorphs that are similar morphologically to Phoma
      and described in Ascochyta, Asteromella, Coniothyrium, Plectophomella,
      Pleurophoma and Pyrenochaeta are included in this study. Phoma-like species,
      which grouped outside the Pleosporineae based on a LSU sequence analysis, are
      transferred to the genera Aposphaeria, Paraconiothyrium and Westerdykella. The
      genera Medicopsis gen. nov. and Nigrograna gen. nov. are introduced to
      accommodate the medically important species formerly known as Pyrenochaeta
      romeroi and Pyrenochaeta mackinnonii, respectively. TAXONOMIC NOVELTIES: New
      genera: Medicopsis Gruyter, Verkley & Crous, Nigrograna Gruyter, Verkley & Crous,
      Paraleptosphaeria Gruyter, Verkley & Crous, Subplenodomus Gruyter, Verkley &
      Crous. New species: Aposphaeria corallinolutea Gruyter, Aveskamp & Verkley,
      Paraconiothyrium maculicutis Verkley & Gruyter. New combinations: Coniothyrium
      carteri (Gruyter & Boerema) Verkley & Gruyter, C. dolichi (Mohanty) Verkley &
      Gruyter, C. glycines (R.B. Stewart) Verkley & Gruyter, C. multiporum (V.H. Pawar,
      P.N. Mathur & Thirum.) Verkley & Gruyter, C. telephii (Allesch.) Verkley &
      Gruyter, Heterospora (Boerema, Gruyter & Noordel.) Gruyter, Verkley & Crous, H.
      chenopodii (Westend.) Gruyter, Aveskamp & Verkley, H. dimorphospora (Speg.)
      Gruyter, Aveskamp & Verkley, Leptosphaeria errabunda (Desm.) Gruyter, Aveskamp &
      Verkley, L. etheridgei (L.J. Hutchison & Y. Hirats.) Gruyter, Aveskamp & Verkley,
      L. macrocapsa (Trail) Gruyter, Aveskamp & Verkley, L. pedicularis (Fuckel)
      Gruyter, Aveskamp & Verkley, L. rubefaciens (Togliani) Gruyter, Aveskamp &
      Verkley, L. sclerotioides (Sacc.) Gruyter, Aveskamp & Verkley, L. sydowii
      (Boerema, Kesteren & Loer.) Gruyter, Aveskamp & Verkley, L. veronicae (Hollos)
      Gruyter, Aveskamp & Verkley, Medicopsis romeroi (Borelli) Gruyter, Verkley &
      Crous, Nigrograna mackinnonii (Borelli) Gruyter, Verkley & Crous,
      Paraconiothyrium flavescens (Gruyter, Noordel. & Boerema) Verkley & Gruyter,
      Paracon. fuckelii (Sacc.) Verkley & Gruyter, Paracon. fusco-maculans (Sacc.)
      Verkley & Gruyter, Paracon. lini (Pass.) Verkley & Gruyter, Paracon. tiliae (F.
      Rudolphi) Verkley & Gruyter, Paraleptosphaeria dryadis (Johanson) Gruyter,
      Aveskamp & Verkley, Paralept. macrospora (Thum.) Gruyter, Aveskamp & Verkley,
      Paralept. nitschkei (Rehm ex G. Winter) Gruyter, Aveskamp & Verkley, Paralept.
      orobanches (Schweinitz: Fr.) Gruyter, Aveskamp & Verkley, Paralept. praetermissa
      (P. Karst.) Gruyter, Aveskamp & Verkley, Plenodomus agnitus (Desm.) Gruyter,
      Aveskamp & Verkley, Plen. biglobosus (Shoemaker & H. Brun) Gruyter, Aveskamp &
      Verkley, Plen. chrysanthemi (Zachos, Constantinou & Panag.) Gruyter, Aveskamp &
      Verkley, Plen. collinsoniae (Dearn. & House) Gruyter, Aveskamp & Verkley, Plen.
      confertus (Niessl ex Sacc.) Gruyter, Aveskamp & Verkley, Plen. congestus (M.T.
      Lucas) Gruyter, Aveskamp & Verkley, Plen. enteroleucus (Sacc.) Gruyter, Aveskamp
      & Verkley, Plen. fallaciosus (Berl.) Gruyter, Aveskamp & Verkley, Plen.
      hendersoniae (Fuckel) Gruyter, Aveskamp & Verkley, Plen. influorescens (Boerema &
      Loer.) Gruyter, Aveskamp & Verkley, Plen. libanotidis (Fuckel) Gruyter, Aveskamp
      & Verkley, Plen. lindquistii (Frezzi) Gruyter, Aveskamp & Verkley, Plen. lupini
      (Ellis & Everh.) Gruyter, Aveskamp & Verkley, Plen. pimpinellae (Lowen & Sivan.)
      Gruyter, Aveskamp & Verkley, Plen. tracheiphilus (Petri) Gruyter, Aveskamp &
      Verkley, Plen. visci (Moesz) Gruyter, Aveskamp & Verkley, Pleospora fallens
      (Sacc.) Gruyter & Verkley, Pleo. flavigena (Constantinou & Aa) Gruyter & Verkley,
      Pleo. incompta (Sacc. & Martelli) Gruyter & Verkley, Pyrenochaetopsis pratorum
      (P.R. Johnst. & Boerema) Gruyter, Aveskamp & Verkley, Subplenodomus apiicola
      (Kleb.) Gruyter, Aveskamp & Verkley, Subplen. drobnjacensis (Bubak) Gruyter,
      Aveskamp & Verkley, Subplen. valerianae (Henn.) Gruyter, Aveskamp & Verkley,
      Subplen. violicola (P. Syd.) Gruyter, Aveskamp & Verkley, Westerdykella capitulum
      (V.H. Pawar, P.N. Mathur & Thirum.) de Gruyter, Aveskamp & Verkley, W.
      minutispora (P.N. Mathur ex Gruyter & Noordel.) Gruyter, Aveskamp & Verkley. New
      names: Pleospora angustis Gruyter & Verkley, Pleospora halimiones Gruyter &
      Verkley.

PMID- 24014898
TI  - Phylogenetic lineages in Pseudocercospora.
AB  - Pseudocercospora is a large cosmopolitan genus of plant pathogenic fungi that are
      commonly associated with leaf and fruit spots as well as blights on a wide range
      of plant hosts. They occur in arid as well as wet environments and in a wide
      range of climates including cool temperate, sub-tropical and tropical regions.
      Pseudocercospora is now treated as a genus in its own right, although formerly
      recognised as either an anamorphic state of Mycosphaerella or having
      mycosphaerella-like teleomorphs. The aim of this study was to sequence the
      partial 28S nuclear ribosomal RNA gene of a selected set of isolates to resolve
      phylogenetic generic limits within the Pseudocercospora complex. From these data,
      14 clades are recognised, six of which cluster in Mycosphaerellaceae.
      Pseudocercospora s. str. represents a distinct clade, sister to Passalora
      eucalypti, and a clade representing the genera Scolecostigmina, Trochophora and
      Pallidocercospora gen. nov., taxa formerly accommodated in the Mycosphaerella
      heimii complex and characterised by smooth, pale brown conidia, as well as the
      formation of red crystals in agar media. Other clades in Mycosphaerellaceae
      include Sonderhenia, Microcyclosporella, and Paracercospora. Pseudocercosporella
      resides in a large clade along with Phloeospora, Miuraea, Cercospora and
      Septoria. Additional clades represent Dissoconiaceae, Teratosphaeriaceae,
      Cladosporiaceae, and the genera Xenostigmina, Strelitziana, Cyphellophora and
      Thedgonia. The genus Phaeomycocentrospora is introduced to accommodate
      Mycocentrospora cantuariensis, primarily distinguished from Pseudocercospora
      based on its hyaline hyphae, broad conidiogenous loci and hila. Host specificity
      was considered for 146 species of Pseudocercospora occurring on 115 host genera
      from 33 countries. Partial nucleotide sequence data for three gene loci, ITS, EF
      1alpha, and ACT suggest that the majority of these species are host specific.
      Species identified on the basis of host, symptomatology and general morphology,
      within the same geographic region, frequently differed phylogenetically,
      indicating that the application of European and American names to Asian taxa, and
      vice versa, was often not warranted. TAXONOMIC NOVELTIES: New genera -
      Pallidocercospora Crous, Phaeomycocentrospora Crous, H.D. Shin & U. Braun; New
      species - Cercospora eucommiae Crous, U. Braun & H.D. Shin, Microcyclospora
      quercina Crous & Verkley, Pseudocercospora ampelopsis Crous, U. Braun & H.D.
      Shin, Pseudocercospora cercidicola Crous, U. Braun & C. Nakash., Pseudocercospora
      crispans G.C. Hunter & Crous, Pseudocercospora crocea Crous, U. Braun, G.C.
      Hunter & H.D. Shin, Pseudocercospora haiweiensis Crous & X. Zhou,
      Pseudocercospora humulicola Crous, U. Braun & H.D. Shin, Pseudocercospora
      marginalis G.C. Hunter, Crous, U. Braun & H.D. Shin, Pseudocercospora ocimi
      basilici Crous, M.E. Palm & U. Braun, Pseudocercospora plectranthi G.C. Hunter,
      Crous, U. Braun & H.D. Shin, Pseudocercospora proteae Crous, Pseudocercospora
      pseudostigmina-platani Crous, U. Braun & H.D. Shin, Pseudocercospora
      pyracanthigena Crous, U. Braun & H.D. Shin, Pseudocercospora ravenalicola G.C.
      Hunter & Crous, Pseudocercospora rhamnellae G.C. Hunter, H.D. Shin, U. Braun &
      Crous, Pseudocercospora rhododendri-indici Crous, U. Braun & H.D. Shin,
      Pseudocercospora tibouchinigena Crous & U. Braun, Pseudocercospora xanthocercidis
      Crous, U. Braun & A. Wood, Pseudocercosporella koreana Crous, U. Braun & H.D.
      Shin; New combinations - Pallidocercospora acaciigena (Crous & M.J. Wingf.) Crous
      & M.J. Wingf., Pallidocercospora crystallina (Crous & M.J. Wingf.) Crous & M.J.
      Wingf., Pallidocercospora heimii (Crous) Crous, Pallidocercospora heimioides
      (Crous & M.J. Wingf.) Crous & M.J. Wingf., Pallidocercospora holualoana (Crous,
      Joanne E. Taylor & M.E. Palm) Crous, Pallidocercospora konae (Crous, Joanne E.
      Taylor & M.E. Palm) Crous, Pallidoocercospora irregulariramosa (Crous & M.J.
      Wingf.) Crous & M.J. Wingf., Phaeomycocentrospora cantuariensis (E.S. Salmon &
      Wormald) Crous, H.D. Shin & U. Braun, Pseudocercospora hakeae (U. Braun & Crous)
      U. Braun & Crous, Pseudocercospora leucadendri (Cooke) U. Braun & Crous,
      Pseudocercospora snelliana (Reichert) U. Braun, H.D. Shin, C. Nakash. & Crous,
      Pseudocercosporella chaenomelis (Y. Suto) C. Nakash., Crous, U. Braun & H.D.
      Shin; Typifications: Epitypifications - Pseudocercospora angolensis (T. Carvalho
      & O. Mendes) Crous & U. Braun, Pseudocercospora araliae (Henn.) Deighton,
      Pseudocercospora cercidis-chinensis H.D. Shin & U. Braun, Pseudocercospora
      corylopsidis (Togashi & Katsuki) C. Nakash. & Tak. Kobay., Pseudocercospora
      dovyalidis (Chupp & Doidge) Deighton, Pseudocercospora fukuokaensis (Chupp) X.J.
      Liu & Y.L. Guo, Pseudocercospora humuli (Hori) Y.L. Guo & X.J. Liu,
      Pseudocercospora kiggelariae (Syd.) Crous & U. Braun, Pseudocercospora lyoniae
      (Katsuki & Tak. Kobay.) Deighton, Pseudocercospora lythri H.D. Shin & U. Braun,
      Pseudocercospora sambucigena U. Braun, Crous & K. Schub., Pseudocercospora
      stephanandrae (Tak. Kobay. & H. Horie) C. Nakash. & Tak. Kobay., Pseudocercospora
      viburnigena U. Braun & Crous, Pseudocercosporella chaenomelis (Y. Suto) C.
      Nakash., Crous, U. Braun & H.D. Shin, Xenostigmina zilleri (A. Funk) Crous;
      Lectotypification - Pseudocercospora ocimicola (Petr. & Cif.) Deighton;
      Neotypifications - Pseudocercospora kiggelariae (Syd.) Crous & U. Braun,
      Pseudocercospora lonicericola (W. Yamam.) Deighton, Pseudocercospora zelkovae
      (Hori) X.J. Liu & Y.L. Guo.

PMID- 24014899
TI  - Species concepts in Cercospora: spotting the weeds among the roses.
AB  - The genus Cercospora contains numerous important plant pathogenic fungi from a
      diverse range of hosts. Most species of Cercospora are known only from their
      morphological characters in vivo. Although the genus contains more than 5 000
      names, very few cultures and associated DNA sequence data are available. In this
      study, 360 Cercospora isolates, obtained from 161 host species, 49 host families
      and 39 countries, were used to compile a molecular phylogeny. Partial sequences
      were derived from the internal transcribed spacer regions and intervening 5.8S
      nrRNA, actin, calmodulin, histone H3 and translation elongation factor 1-alpha
      genes. The resulting phylogenetic clades were evaluated for application of
      existing species names and five novel species are introduced. Eleven species are
      epi-, lecto- or neotypified in this study. Although existing species names were
      available for several clades, it was not always possible to apply North American
      or European names to African or Asian strains and vice versa. Some species were
      found to be limited to a specific host genus, whereas others were isolated from a
      wide host range. No single locus was found to be the ideal DNA barcode gene for
      the genus, and species identification needs to be based on a combination of gene
      loci and morphological characters. Additional primers were developed to
      supplement those previously published for amplification of the loci used in this
      study. TAXONOMIC NOVELTIES: New species - Cercospora coniogrammes Crous & R.G.
      Shivas, Cercospora delaireae C. Nakash., Crous, U. Braun & H.D. Shin, Cercospora
      euphorbiae-sieboldianae C. Nakash., Crous, U. Braun & H.D. Shin, Cercospora
      pileicola C. Nakash., Crous, U. Braun & H.D. Shin, Cercospora vignigena C.
      Nakash., Crous, U. Braun & H.D. Shin. Typifications: epitypifications -
      Cercospora alchemillicola U. Braun & C.F. Hill, Cercospora althaeina Sacc.,
      Cercospora armoraciae Sacc., Cercospora corchori Sawada, Cercospora mercurialis
      Pass., Cercospora olivascens Sacc., Cercospora violae Sacc.; neotypifications -
      Cercospora fagopyri N. Nakata & S. Takim., Cercospora sojina Hara.

PMID- 24014900
TI  - Alternaria redefined.
AB  - Alternaria is a ubiquitous fungal genus that includes saprobic, endophytic and
      pathogenic species associated with a wide variety of substrates. In recent years,
      DNA-based studies revealed multiple non-monophyletic genera within the Alternaria
      complex, and Alternaria species clades that do not always correlate to species
      groups based on morphological characteristics. The Alternaria complex currently
      comprises nine genera and eight Alternaria sections. The aim of this study was to
      delineate phylogenetic lineages within Alternaria and allied genera based on
      nucleotide sequence data of parts of the 18S nrDNA, 28S nrDNA, ITS, GAPDH, RPB2
      and TEF1-alpha gene regions. Our data reveal a Pleospora/Stemphylium clade sister
      to Embellisia annulata, and a well-supported Alternaria clade. The Alternaria
      clade contains 24 internal clades and six monotypic lineages, the assemblage of
      which we recognise as Alternaria. This puts the genera Allewia, Brachycladium,
      Chalastospora, Chmelia, Crivellia, Embellisia, Lewia, Nimbya, Sinomyces,
      Teretispora, Ulocladium, Undifilum and Ybotromyces in synonymy with Alternaria.
      In this study, we treat the 24 internal clades in the Alternaria complex as
      sections, which is a continuation of a recent proposal for the taxonomic
      treatment of lineages in Alternaria. Embellisia annulata is synonymised with
      Dendryphiella salina, and together with Dendryphiella arenariae, are placed in
      the new genus Paradendryphiella. The sexual genera Clathrospora and Comoclathris,
      which were previously associated with Alternaria, cluster within the
      Pleosporaceae, outside Alternaria s. str., whereas Alternariaster, a genus
      formerly seen as part of Alternaria, clusters within the Leptosphaeriaceae.
      Paradendryphiella is newly described, the generic circumscription of Alternaria
      is emended, and 32 new combinations and 10 new names are proposed. A further 10
      names are resurrected, while descriptions are provided for 16 new Alternaria
      sections. TAXONOMIC NOVELTIES: New combinations - Alternaria abundans (E.G.
      Simmons) Woudenb. & Crous, Alternaria alternariae (Cooke) Woudenb. & Crous,
      Alternaria atra (Preuss) Woudenb. & Crous, Alternaria bornmuelleri (Magnus)
      Woudenb. & Crous, Alternaria botrytis (Preuss) Woudenb. & Crous, Alternaria
      caespitosa (de Hoog & C. Rubio) Woudenb. & Crous, Alternaria cantlous (Yong Wang
      bis & X.G. Zhang) Woudenb. & Crous, Alternaria caricis (E.G. Simmons) Woudenb. &
      Crous, Alternaria cinerea (Baucom & Creamer) Woudenb. & Crous, Alternaria
      didymospora (Munt.-Cvetk.) Woudenb. & Crous, Alternaria fulva (Baucom & Creamer)
      Woudenb. & Crous, Alternaria hyacinthi (de Hoog & P.J. Mull. bis) Woudenb. &
      Crous, Alternaria indefessa (E.G. Simmons) Woudenberg & Crous, Alternaria
      leptinellae (E.G. Simmons & C.F. Hill) Woudenb. & Crous, Alternaria lolii (E.G.
      Simmons & C.F. Hill) Woudenb. & Crous, Alternaria multiformis (E.G. Simmons)
      Woudenb. & Crous, Alternaria obclavata (Crous & U. Braun) Woudenb. & Crous,
      Alternaria obovoidea (E.G. Simmons) Woudenb. & Crous, Alternaria oudemansii (E.G.
      Simmons) Woudenb. & Crous, Alternaria oxytropis (Q. Wang, Nagao & Kakish.)
      Woudenb. & Crous, Alternaria penicillata (Corda) Woudenb. & Crous, Alternaria
      planifunda (E.G. Simmons) Woudenb. & Crous, Alternaria proteae (E.G. Simmons)
      Woudenb. & Crous, Alternaria scirpinfestans (E.G. Simmons & D.A. Johnson)
      Woudenb. & Crous, Alternaria scirpivora (E.G. Simmons & D.A. Johnson) Woudenb. &
      Crous, Alternaria septospora (Preuss) Woudenb. & Crous, Alternaria slovaca (Svob.
      Pol., L. Chmel & Bojan.) Woudenb. & Crous, Alternaria subcucurbitae (Yong Wang
      bis & X.G. Zhang) Woudenb. & Crous, Alternaria tellustris (E.G. Simmons) Woudenb.
      & Crous, Alternaria tumida (E.G. Simmons) Woudenb. & Crous, Paradendryphiella
      salina (G.K. Sutherl.) Woudenb. & Crous, Paradendryphiella arenariae (Nicot)
      Woudenb. & Crous. New names - Alternaria aspera Woudenb. & Crous, Alternaria
      botryospora Woudenb. & Crous, Alternaria brassicae-pekinensis Woudenb. & Crous,
      Alternaria breviramosa Woudenb. & Crous, Alternaria chlamydosporigena Woudenb. &
      Crous, Alternaria concatenata Woudenb. & Crous, Alternaria embellisia Woudenb. &
      Crous, Alternaria heterospora Woudenb. & Crous, Alternaria papavericola Woudenb.
      & Crous, Alternaria terricola Woudenb. & Crous. Resurrected names - Alternaria
      cetera E.G. Simmons, Alternaria chartarum Preuss, Alternaria consortialis (Thum.)
      J.W. Groves & S. Hughes, Alternaria cucurbitae Letendre & Roum., Alternaria
      dennisii M.B. Ellis, Alternaria eureka E.G. Simmons, Alternaria gomphrenae
      Togashi, Alternaria malorum (Ruehle) U. Braun, Crous & Dugan, Alternaria
      phragmospora Emden, Alternaria scirpicola (Fuckel) Sivan. New sections, all in
      Alternaria - sect. Chalastospora Woudenb. & Crous, sect. Cheiranthus Woudenb. &
      Crous, sect. Crivellia Woudenb. & Crous, sect. Dianthicola Woudenb. & Crous,
      sect. Embellisia Woudenb. & Crous, sect. Embellisioides Woudenb. & Crous, sect.
      Eureka Woudenb. & Crous, sect. Infectoriae Woudenb. & Crous, sect. Japonicae
      Woudenb. & Crous, sect. Nimbya Woudenb. & Crous, sect. Phragmosporae Woudenb. &
      Crous, sect. Pseudoulocladium Woudenb. & Crous, sect. Teretispora Woudenb. &
      Crous, sect. Ulocladioides Woudenb. & Crous, sect. Ulocladium Woudenb. & Crous,
      sect. Undifilum Woudenb. & Crous. New genus - Paradendryphiella Woudenb. & Crous.

PMID- 24014892
TI  - Hematopoietic stem cell gene therapy:assessing the relevance of preclinical
      models.

PMID- 24014901
TI  - A new approach to species delimitation in Septoria.
AB  - Septoria is a large genus of asexual morphs of Ascomycota causing leaf spot
      diseases of many cultivated and wild plants. Host specificity has long been a
      decisive criterium in species delimitation in Septoria, mainly because of the
      paucity of useful morphological characters and the high level of variation
      therein. This study aimed at improving the species delimitation of Septoria by
      adopting a polyphasic approach, including multilocus DNA sequencing and
      morphological analyses on the natural substrate and in culture. To this end 365
      cultures preserved in CBS, Utrecht, The Netherlands, among which many new
      isolates obtained from fresh field specimens were sequenced. Herbarium material
      including many types was also studied. Full descriptions of the morphology in
      planta and in vitro are provided for 57 species. DNA sequences were generated for
      seven loci, viz. nuclear ITS and (partial) LSU ribosomal RNA genes, RPB2, actin,
      calmodulin, Btub, and EF. The robust phylogeny inferred showed that the septoria
      like fungi are distributed over three main clades, establishing the genera
      Septoria s. str., Sphaerulina, and Caryophylloseptoria gen. nov. Nine new
      combinations and one species, Sphaerulina tirolensis sp. nov. were proposed. It
      is demonstrated that some species have wider host ranges than expected, including
      hosts from more than one family. Septoria protearum, previously only associated
      with Proteaceae was found to be also associated with host plants from six
      additional families of phanerogams and cryptogams. To our knowledge this is the
      first study to provide DNA-based evidence that multiple family-associations occur
      for a single species in Septoria. The distribution of host families over the
      phylogenetic tree showed a highly dispersed pattern for 10 host plant families,
      providing new insight into the evolution of these fungi. It is concluded that
      trans-family host jumping is a major force driving the evolution of Septoria and
      Sphaerulina. TAXONOMIC NOVELTIES: New genus - Caryophylloseptoria Verkley,
      Quaedvlieg & Crous; New species - Sphaerulina tirolensis Verkley, Quaedvlieg &
      Crous; New combinations - Caryophylloseptoria lychnidis (Desm.) Verkley,
      Quaedvlieg & Crous, Caryophylloseptoria silenes (Westend.) Verkley, Quaedvlieg &
      Crous, Caryophylloseptoria spergulae (Westend.) Verkley, Quaedvlieg & Crous,
      Sphaerulina aceris (Lib.) Verkley, Quaedvlieg & Crous, Sphaerulina cornicola
      (DC.: Fr.) Verkley, Quaedvlieg & Crous, Sphaerulina gei (Roberge ex Desm.)
      Verkley, Quaedvlieg & Crous, Sphaerulina hyperici (Roberge ex Desm.) Verkley,
      Quaedvlieg & Crous, Sphaerulina frondicola (Fr.) Verkley, Quaedvlieg & Crous,
      Sphaerulina socia (Pass.) Quaedvlieg, Verkley & Crous; Epitypifications
      (basionyms) - Ascochyta lysimachiae Lib., Septoria astragali Roberge ex Desm.,
      Septoria cerastii Roberge ex Desm., Septoria clematidis Roberge ex Desm.,
      Septoria cruciatae Roberge ex Desm., Septoria spergulae Westend., Septoria
      epilobii Westend., Septoria galeopsidis Westend., Septoria gei Roberge ex Desm.,
      Septoria hyperici Roberge ex Desm., Septoria rubi Westend., Septoria senecionis
      Westend., Septoria urticae Roberge ex Desm.

PMID- 24014902
TI  - Sizing up Septoria.
AB  - Septoria represents a genus of plant pathogenic fungi with a wide geographic
      distribution, commonly associated with leaf spots and stem cankers of a broad
      range of plant hosts. A major aim of this study was to resolve the phylogenetic
      generic limits of Septoria, Stagonospora, and other related genera such as
      Sphaerulina, Phaeosphaeria and Phaeoseptoria using sequences of the the partial
      28S nuclear ribosomal RNA and RPB2 genes of a large set of isolates. Based on
      these results Septoria is shown to be a distinct genus in the Mycosphaerellaceae,
      which has mycosphaerella-like sexual morphs. Several septoria-like species are
      now accommodated in Sphaerulina, a genus previously linked to this complex.
      Phaeosphaeria (based on P. oryzae) is shown to be congeneric with Phaeoseptoria
      (based on P. papayae), which is reduced to synonymy under the former. Depazea
      nodorum (causal agent of nodorum blotch of cereals) and Septoria avenae (causal
      agent of avenae blotch of barley and rye) are placed in a new genus,
      Parastagonospora, which is shown to be distinct from Stagonospora (based on S.
      paludosa) and Phaeosphaeria. Partial nucleotide sequence data for five gene loci,
      ITS, LSU, EF-1alpha, RPB2 and Btub were generated for all of these isolates. A
      total of 47 clades or genera were resolved, leading to the introduction of 14 new
      genera, 36 new species, and 19 new combinations. TAXONOMIC NOVELTIES: New genera 
      Acicuseptoria Quaedvlieg, Verkley & Crous, Cylindroseptoria Quaedvlieg, Verkley
      & Crous, Kirstenboschia Quaedvlieg, Verkley & Crous, Neoseptoria Quaedvlieg,
      Verkley & Crous, Neostagonospora Quaedvlieg, Verkley & Crous, Parastagonospora
      Quaedvlieg, Verkley & Crous, Polyphialoseptoria Quaedvlieg, R.W. Barreto, Verkley
      & Crous, Ruptoseptoria Quaedvlieg, Verkley & Crous, Septorioides Quaedvlieg,
      Verkley & Crous, Setoseptoria Quaedvlieg, Verkley & Crous, Stromatoseptoria
      Quaedvlieg, Verkley & Crous, Vrystaatia Quaedvlieg, W.J. Swart, Verkley & Crous,
      Xenobotryosphaeria Quaedvlieg, Verkley & Crous, Xenoseptoria Quaedvlieg, H.D.
      Shin, Verkley & Crous. New species - Acicuseptoria rumicis Quaedvlieg, Verkley &
      Crous, Caryophylloseptoria pseudolychnidis Quaedvlieg, H.D. Shin, Verkley &
      Crous, Coniothyrium sidae Quaedvlieg, Verkley, R.W. Barreto & Crous, Corynespora
      leucadendri Quaedvlieg, Verkley & Crous, Cylindroseptoria ceratoniae Quaedvlieg,
      Verkley & Crous, Cylindroseptoria pistaciae Quaedvlieg, Verkley & Crous,
      Kirstenboschia diospyri Quaedvlieg, Verkley & Crous, Neoseptoria caricis
      Quaedvlieg, Verkley & Crous, Neostagonospora caricis Quaedvlieg, Verkley & Crous,
      Neostagonospora elegiae Quaedvlieg, Verkley & Crous, Paraphoma dioscoreae
      Quaedvlieg, H.D. Shin, Verkley & Crous, Parastagonospora caricis Quaedvlieg,
      Verkley & Crous, Parastagonospora poae Quaedvlieg, Verkley & Crous, Phlyctema
      vincetoxici Quaedvlieg, Verkley & Crous, Polyphialoseptoria tabebuiae
      serratifoliae Quaedvlieg, Alfenas & Crous, Polyphialoseptoria terminaliae
      Quaedvlieg, R.W. Barreto, Verkley & Crous, Pseudoseptoria collariana Quaedvlieg,
      Verkley & Crous, Pseudoseptoria obscura Quaedvlieg, Verkley & Crous,
      Sclerostagonospora phragmiticola Quaedvlieg, Verkley & Crous, Septoria cretae
      Quaedvlieg, Verkley & Crous, Septoria glycinicola Quaedvlieg, H.D. Shin, Verkley
      & Crous, Septoria oenanthicola Quaedvlieg, H.D. Shin, Verkley & Crous, Septoria
      pseudonapelli Quaedvlieg, H.D. Shin, Verkley & Crous, Setophoma chromolaenae
      Quaedvlieg, Verkley, R.W. Barreto & Crous, Setoseptoria phragmitis Quaedvlieg,
      Verkley & Crous, Sphaerulina amelanchier Quaedvlieg, Verkley & Crous, Sphaerulina
      pseudovirgaureae Quaedvlieg, Verkley & Crous, Sphaerulina viciae Quaedvlieg, H.D.
      Shin, Verkley & Crous, Stagonospora duoseptata Quaedvlieg, Verkley & Crous,
      Stagonospora perfecta Quaedvlieg, Verkley & Crous, Stagonospora pseudocaricis
      Quaedvlieg, Verkley, Gardiennet & Crous, Stagonospora pseudovitensis Quaedvlieg,
      Verkley & Crous, Stagonospora uniseptata Quaedvlieg, Verkley & Crous, Vrystaatia
      aloeicola Quaedvlieg, Verkley, W.J. Swart & Crous, Xenobotryosphaeria
      calamagrostidis Quaedvlieg, Verkley & Crous, Xenoseptoria neosaccardoi
      Quaedvlieg, H.D. Shin, Verkley & Crous. New combinations - Parastagonospora
      avenae (A.B. Frank) Quaedvlieg, Verkley & Crous, Parastagonospora nodorum (Berk.)
      Quaedvlieg, Verkley & Crous, Phaeosphaeria papayae (Speg.) Quaedvlieg, Verkley &
      Crous, Pseudocercospora domingensis (Petr. & Cif.) Quaedvlieg, Verkley & Crous,
      Ruptoseptoria unedonis (Roberge ex Desm.) Quaedvlieg, Verkley & Crous,
      Septorioides pini-thunbergii (S. Kaneko) Quaedvlieg, Verkley & Crous, Sphaerulina
      abeliceae (Hiray.) Quaedvlieg, Verkley & Crous, Sphaerulina azaleae (Voglino)
      Quaedvlieg, Verkley & Crous, Sphaerulina berberidis (Niessl) Quaedvlieg, Verkley
      & Crous, Sphaerulina betulae (Pass.) Quaedvlieg, Verkley & Crous, Sphaerulina
      cercidis (Fr.) Quaedvlieg, Verkley & Crous, Sphaerulina menispermi (Thum.)
      Quaedvlieg, Verkley & Crous, Sphaerulina musiva (Peck) Quaedvlieg, Verkley &
      Crous, Sphaerulina oxyacanthae (Kunze & J.C. Schmidt) Quaedvlieg, Verkley &
      Crous, Sphaerulina patriniae (Miura) Quaedvlieg, Verkley & Crous, Sphaerulina
      populicola (Peck) Quaedvlieg, Verkley & Crous, Sphaerulina quercicola (Desm.)
      Quaedvlieg, Verkley & Crous, Sphaerulina rhabdoclinis (Butin) Quaedvlieg, Verkley
      & Crous, Stromatoseptoria castaneicola (Desm.) Quaedvlieg, Verkley & Crous.
      Typifications: Epitypifications - Phaeosphaeria oryzae I. Miyake, Phaeoseptoria
      papayae Speg.; Neotypification - Hendersonia paludosa Sacc. & Speg.

PMID- 24014903
TI  - Regulatory changes in conduct of clinical trials: a need for review.

PMID- 24014904
TI  - Development of an in vitro cell culture model to study milk to plasma ratios of
      therapeutic drugs.
AB  - OBJECTIVE: To create an in vitro cell culture model to predict the M/P
      (concentration of drug in milk/concentration in maternal plasma) ratios of
      therapeutic drugs viz. rifampicin, theophylline, paracetamol, and aspirin.
      MATERIALS AND METHODS: An in vitro cell culture model using CIT3 cells (mouse
      mammary epithelial cells) was created by culturing the cells on transwells. The
      cells formed an integral monolayer, allowing only transcellular transport as it
      happens in vivo. Functionality of the cells was confirmed through scanning
      electron microscopy. Time wise transfer of the study drugs from plasma to milk
      was studied and compared with actual (in vivo) M/P ratios obtained at reported
      tmax for the respective drugs. RESULTS: The developed model mimicked two
      important intrinsic factors of mammary epithelial cells viz. secretory and tight
      junction properties and also the passive route of drug transport. The in vitro
      M/P ratios at reported tmax were 0.23, 0.61, 0.87, and 0.03 respectively, for
      rifampicin, theophylline, paracetamol, and salicylic acid as compared to 0.29,
      0.65, 0.65, and 0.22, respectively, in vitro. CONCLUSION: Our preliminary effort
      to develop an in vitro physiological model showed promising results. Transfer
      rate of the drugs using the developed model compared well with the transfer
      potential seen in vivo except for salicylic acid, which was transferred in far
      lower concentration in vitro. The model has a potential to be developed as a non
      invasive alternative to the in vitro technique for determining the transfer of
      therapeutic drugs into breast milk.

PMID- 24014905
TI  - Pharmacokinetics of single-dose primaquine in patients with chronic kidney
      dysfunction.
AB  - AIM: The pharmacokinetics of primaquine has not been studied in special
      populations. Being a basic compound, preferential binding to alpha-1 acid
      glycoprotein and substrate for P-glycoprotein, may predispose the drug for an
      altered pharmacokinetics in states of renal dysfunction. This study attempts to
      evaluate the pharmacokinetics of a single oral dose (15 mg) of primaquine in
      severely impaired renal function and end stage renal dysfunction patients
      compared to healthy participants. MATERIALS AND METHODS: Twelve patients each
      with chronic kidney disease classified as either Stage IV or V (not on dialysis)
      were recruited. Data from 12 healthy participants was used as concurrent
      controls. Serial blood collections were performed following a single dose 15 mg
      Primaquine orally. Primaquine concentrations were measured in the plasma using a
      validated HPLC method. RESULTS: The Cmax [median (range) in ng/ml] was 29.3 (14.6
      104.3), 40.3 (14.8 - 78.6), and 49.8 (15 - 169.6) and the tmax [median (range) in
      hours] was 3.0 (1.0- 6.0), 2.0 (1.5 - 8) and 2.0 (1.0 - 4.0) for healthy and
      stage IV, V (not on dialysis) CKD participants, respectively. No statistically
      significant difference was observed in any of the pharmacokinetic parameters
      between healthy, stage IV and V CKD participants. CONCLUSION: Pharmacokinetics of
      single oral dose primaquine (15 mg) does not appear to be altered in patients
      with severely impaired renal function and end stage renal dysfunction. A change
      in dose or frequency of the drug administration perhaps may not be required in
      this population.

PMID- 24014906
TI  - A comparative study of efficacy and safety of gabapentin versus amitriptyline as
      coanalgesics in patients receiving opioid analgesics for neuropathic pain in
      malignancy.
AB  - OBJECTIVE: To assess the efficacy and safety of gabapentin and amitriptyline
      along with opioids in patients suffering from neuropathic pain in malignancy.
      MATERIALS AND METHODS: Eighty-eight adult patients between 18 and 70 years of age
      with neuropathic pain in stage III malignant disease, matched for baseline
      charactistics, were randomly assigned to two groups. Group A received oral
      tramadol and gabapentin and group B received oral tramadol and amitriptyline. The
      treatment duration of each patient was 6 months. Visual analog scale (VAS) was
      the primary efficacy parameter. Verbal rating scale (VRS) score, percentage of
      pain relief (PPR), and global pain score (GPS) were the secondary efficacy
      parameters. Oral morphine tablets or fentanyl transdermal patch were used as
      rescue medication. Data analysis was carried out in Graph Pad instat. RESULTS:
      There was decline in VAS pain score from baseline in both the groups in the early
      phase of the study though there was no statistically detectable difference
      between them at any study point. Similar changes were seen in the secondary
      efficacy parameters too. Thus both the drugs were effective in providing relief
      to cancer patients with neuropathic pain though there was no statistically
      detectable difference in efficacy between them. Six patients in group A and eight
      patients in group B required rescue medication. A total of 12 subjects in the
      gabapentin group and 15 subjects in the amitriptyline group experienced adverse
      events which were of mild to moderate grades. CONCLUSIONS: Amitriptyline may be a
      suitable alternative for management of neuropathic pain in cancer patients
      although gabapentin is widely used for this purpose. The lower cost of
      amitriptyline may favor patient compliance with lesser number of drop-outs.

PMID- 24014907
TI  - Effect of thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage
      in rat kidney.
AB  - OBJECTIVES: The biochemical effects of thiamine pyrophosphate on ischemia
      reperfusion (IR) induced oxidative damage and DNA mutation in rat kidney tissue
      were investigated, and compared to thiamine. MATERIALS AND METHODS: Rats were
      divided into four groups: renal ischemia-reperfusion (RIR); thiamine
      pyrophosphate + RIR (TPRIR); thiamine + RIR (TRIR); and sham group (SG). RESULTS:
      The results of biochemical experiments have shown that malondialdehyde (MDA)
      levels in rat kidney tissue after TRIR and TPRIR treatment were 7.2 +/- 0.5 (P >
      0.05) and 3.3 +/- 0.3 (P < 0.0001) MUmol/g protein, respectively. The MDA levels
      in the SG rat kidney tissue and in RIR group were 3.6 +/- 0.2 (P < 0.0001) and
      7.6 +/- 0.6 MUmol/g protein, respectively. Total glutathione (tGSH) levels in
      TRIR, TPRIR, SG, and RIR animal groups were 2.2 +/- 0.3 (P > 0.05), 5.8 +/- 0.4
      (P < 0.0001), 6.2 +/- 0.2 (P < 0.0001), and 1.7 +/- 0.2 nmol/g protein,
      respectively. In the TRIR, TPRIR, SG, and RIR animal groups; 8-hydroxyguanine (8
      OHGua)/Gua levels, which indicate mutagenic DNA, were 1.75 +/- 0.12 (P > 0.05),
      0.93 +/- 0.1 (P < 0.0001), 0.85 +/- 0.08 (P < 0.0001), and 1.93 +/- 0.24 pmol/L,
      respectively. CONCLUSIONS: It has been shown that thiamine pyrophosphate prevents
      increase in mutagenic DNA in IR induced oxidative damage, whereas thiamine does
      not have this effect.

PMID- 24014908
TI  - Effect of methylprednisolone on bone mineral density in rats with ovariectomy
      induced bone loss and suppressed endogenous adrenaline levels by metyrosine.
AB  - OBJECTIVES: In this study, effect of methylprednisolone on bone mineral density
      (BMD) was investigated in rats with overiectomy induced bone lose and suppressed
      endogenous adrenalin levels, and compared to alendronate. MATERIALS AND METHODS:
      Severity of bone loss in the examined material (femur bones) was evaluated by BMD
      measurement. RESULTS: The group with the highest BMD value was
      metyrosinemetyrosine + methylprednisolone combination (0.151 g/cm(2)), while that
      with the lowest BMD was methylprednisolone (0.123 g/cm(2)). Alendronate was
      effective only when used alone in ovariectomized rats (0.144 g/cm(2)), but not
      when used in combination with methylprednisolone (0.124 g/cm(2)). In the
      ovariectomized rat group which received only metyrosine, BMD value was
      statistically indifferent from ovariectomized control group. CONCLUSIONS:
      Methylprednisolone protected bone loss in rats with suppressed adrenaline levels
      because of metyrosinemetyrosine.

PMID- 24014909
TI  - Antidepressant-like effect of novel 5-HT3 receptor antagonist N-n-butyl-3
      ethoxyquinoxalin-2-carboxamide (6p): an approach using rodent behavioral
      antidepressant tests.
AB  - OBJECTIVE: The present study was designed to investigate the antidepressant
      potential of N-n-butyl-3-ethoxyquinoxalin-2-carboxamide (6p), a novel 5-HT3
      receptor antagonist in rodent behavioral models of depression. MATERIALS AND
      METHODS: The compound 6p was examined in various behavioral models like forced
      swim test (FST), tail suspension test (TST), mechanistic models [5
      hydroxytryptophan (5-HTP)-induced head twitch and reserpine-induced hypothermia
      (RIH)], and in chronic surgery model-olfactory bulbectomy in rats. RESULTS:
      Compound 6p (1, 2, and 4 mg/kg, i.p.) exhibited antidepressant-like effect in FST
      and TST after acute treatment without having an effect on baseline locomotor
      activity. Moreover, 6p (2 mg/kg, i.p.), potentiated the 5-HTP-induced head twitch
      responses in mice and inhibited the RIH in rats. Chronic treatment (14 days) with
      6p (1 and 2 mg/kg, p.o.) and paroxetine (10 mg/kg, p.o.) in rats significantly
      reversed the behavioral anomalies induced by bilateral olfactory bulbectomy using
      open field exploration. CONCLUSION: The preliminary studies reveal that compound
      6p exhibits antidepressant-like effect in behavioral rodent models of depression.

PMID- 24014910
TI  - Amelioration of cisplatin-induced nephrotoxicity by statins.
AB  - OBJECTIVES: This study aimed to investigate the protective effect of simvastatin
      (SIM) and rosuvastatin (RST) on cisplatin (CIS)-induced nephrotoxicity. MATERIALS
      AND METHODS: Adult female Wistar rats were divided into six groups: control group
      (Group 1) received 0.5% sodium carboxy methyl cellulose, group 2 and group 3
      received SIM and RST for 10 days, respectively, and group 4 was injected single
      dose of CIS (7 mg/kg, i.p.). Group 5 and 6 were treated with SIM (10 mg/kg, p.o.)
      and RST (10 mg/kg, p.o.) for 10 days, respectively. All groups received cisplatin
      on the 5(th) day of treatment. Renal function tests like serum creatinine, urea,
      BUN, albumin, calcium, uric acid and magnesium, serum lipids, and markers of
      oxidative stress such as renal malondialdehyde (MDA) level and superoxide
      dismutase (SOD) and catalase (CAT) activities were measured. All tissues were
      investigated for histopathological changes. RESULT: CIS reduced the renal
      function, which was reflected with significant increase in serum urea, BUN, serum
      creatinine, uric acid and also significant decrease serum calcium, magnesium,
      albumin levels. In addition, cisplatin caused renal tubular damage with a higher
      MDA level, depletion of SOD and CAT activity, and elevation of serum lipids. SIM
      or RST ameliorate CIS induced renal damage due to improvement in renal function,
      oxidative stress, suppression of serum lipids, and histological alteration.
      CONCLUSIONS: This finding suggests that simvastatin and rosuvastatin may have a
      protective effect against cisplatin-induced kidney damage via amelioration of
      lipid peroxidation as well as due to improvement of renal function, and lipid
      lowering effects.

PMID- 24014911
TI  - Anticoagulant effect of Huisheng Oral Solution in a rat model of thrombosis.
AB  - OBJECTIVE: To investigate whether Huisheng Oral Solution has an anticoagulant
      effect in a rat model of thrombosis. MATERIALS AND METHODS: A total of 40 male SD
      rats were equally and randomly divided into four groups: blank group, model
      group, and two treatment groups (A and B). Rats were subcutaneously injected with
      carrageenan to induce thrombosis. Rats in the treatment group A were
      intragastrically administered with Huisheng Oral Solution at a dose of 2 ml/100 g
      body weight (once per 8 hours), 72 hours after carrageenan injection, while those
      in the treatment group B were administered with Huisheng Oral Solution both 72
      hours before and after induction of thrombosis. Blood samples were collected 24,
      48, and 72 hours after carrageenan injection for measurements of prothrombin time
      (PT), activated partial thromboplastin time (APTT), international normalized
      ratio (INR), fibrinogen (FIB), prothrombin activity (PTA), platelets (PLT),
      fibrin degradation products (FDPs), and D-dimer. Lung, liver, and mesentery
      samples were taken 72 hours after carrageenan injection for histopathological
      analysis. The numbers of microthrombi in sections of different tissue samples
      were counted under a microscope. Blood parameters among each group were compared
      using the Welch test, the Kruskal-Wallis test, or the SNK test after testing for
      normality, while the number of microthrombi was compared using the Bonferroni
      test. RESULTS: Compared to those in the model group, PT, APTT, and INR were
      significantly prolonged or increased while FIB was significantly reduced at the
      majority of time points in the two treatment groups (P < 0.05 for all). The
      levels of FDPs and D-dimer and PLT counts at the majority of time points were
      significantly lower (P < 0.05 for all), and the numbers of microthrombi in lung,
      liver, and mesentery samples were significantly decreased (P < 0.05 for all) in
      the two treatment groups. The above parameters at the majority of time points
      showed no significant differences between the two treatment groups. CONCLUSIONS:
      Huisheng Oral Solution can significantly improve coagulation parameters,
      fibrinolysis parameters, and PLT count, and reduce blood hypercoagulability and
      microthrombosis, suggesting that Huisheng Oral Solution has an anticoagulant
      effect in a rat model of thrombosis.

PMID- 24014912
TI  - A study to investigate capsaicin-induced pressure response in vagotomized rats.
AB  - OBJECTIVES: Capsaicin is used to evoke pulmonary C reflexes and produces complex
      pressure responses along with apnea/tachypnea, and bradycardia. In the present
      study, the mechanisms involved in capsaicin-induced pressure responses were
      explored. MATERIALS AND METHODS: Tracheal, jugular venous, and femoral artery
      cannulations were performed in anesthetized adult rats. Blood pressure,
      respiratory excursions, and electrocardiogram were recorded. Cardiorespiratory
      reflex changes evoked by jugular venous injection of capsaicin (10 MUg/kg) were
      recorded in vagotomized and antagonist pretreated animals. RESULTS: Capsaicin
      produced triphasic pressure response exhibiting immediate hypotension,
      intermediate recovery, and delayed hypotension. Time-matched respiratory changes
      showed apnea, bradypnea, and tachypnea, respectively. Bradycardia occurred at
      immediate and intermediate phases. After vagotomy, immediate hypotension was
      abolished; the intermediate recovery was potentiated as hypertensive response;
      and the delayed hypotension persisted. In case of respiration, the immediate
      bradypnea persisted and delayed tachypnea was abolished; while heart rate changes
      at immediate and intermediate phases were abolished. Antagonists of alpha1
      adrenoceptor (prazosin or terazosin, 0.5 mg/kg), beta-adrenoceptor (propranolol,
      1 mg/kg), AT1 receptor (losartan, 10 mg/kg) and Ca(2+) channel (diltiazem, 1
      mg/kg) failed to block the capsaicin-induced intermediate hypertensive response
      in vagotomized animals. CONCLUSIONS: These observations implicate the existence
      of mechanisms other than adrenergic, angiotensinergic, or Ca(2+) channel
      dependent mechanisms for mediating the capsaicin-induced intermediate
      hypertensive response in vagotomized animals.

PMID- 24014913
TI  - Involvement of opioid and monoaminergic pain pathways in Aegle marmelos induced
      analgesia in mice.
AB  - OBJECTIVE: To study analgesic activity and to evaluate the involvement of opioid
      and monoamines in the antinociceptive activity of methanol extract of leaves of
      Aegle marmelos. MATERIALS AND METHODS: Analgesic activity of methanol extract
      (ME) of A. marmelos alone (75,150 and 300 mg/kg orally) and in combination with
      morphine or venlafaxine (subanalgesic) were studied using tail flick test and
      acetic acid-induced writhing in mice. The effect of pre-treatment with opioid
      antagonist naltrexone 1mg/kg was also studied on antinociception induced due to
      ME. RESULT: ME produced a dose-dependent significant antinociceptive activity in
      the tail flick test and acetic acid-induced writhing in mice. (P<0.05)
      Administration of subanalgesic dose of ME with morphine or venlafaxine also
      resulted in significant (P<0.05) antinociceptive activity in both the pain
      models. Pre-treatment with naltrexone inhibited analgesic activity induced by ME
      alone and combination with morphine or venlafaxine. CONCLUSION: A.marmelos in
      induced antinociception is mediated through both opioid and monoaminergic pain
      pathways, suggest its possible use in chronic pain.

PMID- 24014914
TI  - Protective effect of Clerodendrum colebrookianum Walp., on acute and chronic
      inflammation in rats.
AB  - AIM: To evaluate antioxidant, anti-inflammatory potential of the aqueous extracts
      and its aqueous, n-butanol, ethyl-acetate, and chloroform fractions of
      Clerodendrum colebrookianum Walp. leaves. MATERIALS AND METHODS: In this present
      study, all the test samples were evaluated on in-vivo inflammatory model such as
      carrageenan and histamine-induced acute-inflammation and cotton pellet induced
      granuloma formation in albino male rats. Test samples were also employed in in
      vitro assays like DPPH free radical scavenging activity and COX inhibition assay.
      RESULTS: The test samples at the dose of 200mg/kg/p.o. were found to cause
      significant inhibition of carrageenan and histamine-induced inflammation and
      cotton pallet-induced granuloma formation on acute and chronic inflammation in
      rats. The test samples, except n-butanol fraction, exhibited inhibitory effect
      for both COX-1 and COX-2, in in-vitro assay but their percentage of inhibition
      values differs from each other. The test samples (aqueous extracts, aqueous, n
      butanol, ethyl-acetate, and chloroform fractions) at 100 MUg concentration
      exhibits 54.37%, 33.88%, 62.85%, 56.28%, and 57.48% DPPH radical-scavenging
      effect respectively in in-vitro antioxidant study. CONCLUSION: These observations
      established the anti-inflammatory effect of C. colebrookianum leaves in acute and
      chronic stages of inflammation by free radical scavenging and inhibition of COX-1
      and COX-2.

PMID- 24014915
TI  - Cytotoxic activity of aqueous extracts of Anogeissus leiocarpus and Terminalia
      avicennioides root barks against Ehrlich ascites carcinoma cells.
AB  - OBJECTIVES: Folkloric claims on the use of a mixture of Anogeissus leiocarpus and
      Terminalia avicennioides root barks in tumor management exist without scientific
      evidence. This study aimed at investigating the phytochemical constituents and in
      vitro antiproliferative activity of these plants and their mixture. MATERIALS AND
      METHODS: Phytochemical screening was carried out on the aqueous extracts after
      which various concentrations (0 to 1 000 MUg/ml) were incubated with Ehrlich
      ascites carcinoma cell lines for 3 and 24 hours. RESULTS: The extracts contained
      alkaloids, tannins, flavonoids, phenolics, saponins, phlobatannins, and terpenes.
      The separate extracts and their 1:1 mixture significantly (P<0.05) decreased the
      computed percentage viability of the cell lines in a dose- and time-dependent
      manner. CONCLUSIONS: The antiproliferative activity may be due to the presence of
      the bioactive compounds in the extracts and has a potential in the management of
      tumor.

PMID- 24014916
TI  - Antidepressant-like action of the hydromethanolic flower extract of Tagetes
      erecta L. in mice and its possible mechanism of action.
AB  - OBJECTIVE: Tagetes erecta, the marigold, has commercial and ethnomedicinal use;
      however, reports concerning its efficacy for the treatment of depression are
      lacking. This study was carried out to elucidate the antidepressant effect of
      hydromethanolic flower extract of T. erecta. MATERIALS AND METHODS:
      Hydromethanolic extract of flowers of Tagetes erecta was subjected to preliminary
      phytochemical screening. The extract (12.5, 25, and 50 mg/kg, i.p.) was evaluated
      for antidepressant effect using forced swim test in mice. The mechanism of
      antidepressant action was further examined using different drugs and imipramine
      was used as standard drug. RESULTS: T. erecta significantly inhibited the
      immobility period in forced swim test in mice P<0.05). T. erecta (25 mg/kg, i.p.)
      enhanced the anti-immobility effect of antidepressant drugs like imipramine,
      fluoxetine, and p-chlorophenylalanine, an inhibitor of serotonin synthesis
      significantly attenuated its antidepressant effect. The antidepressant effect of
      T. erecta in the forced swim test was prevented by pretreatment with L-arginine
      and sildenafil, whereas pretreatment of mice with nitric oxide synthase
      inhibitors potentiated the action. Pentazocine, a high-affinity sigma receptor
      agonist, produced synergism with effective dose of T. erecta while progesterone,
      a sigma receptor antagonist, reversed the antidepressant effect of T. erecta.
      However, the locomotor activity was not affected at tested doses. CONCLUSIONS:
      Serotonergic, nitrergic pathway, and sigma receptors are possibly involved in
      mediating antidepressant action of T. erecta in mouse forced swim test.

PMID- 24014917
TI  - Evaluation of anti-inflammatory effect of statins in chronic periodontitis.
AB  - OBJECTIVES: Statins are the group of lipid-lowering drugs commonly used to
      control cardiovascular and cerebrovascular diseases. Statins have potential anti
      inflammatory effect by blocking the intermediate metabolites of the mevalonate
      pathway. The objective of this study was to evaluate the anti-inflammatory effect
      of statin medication in chronic periodontitis patients. MATERIALS AND METHODS:
      Thirty patients of age group between 40 and 60 years were selected from the
      outpatient pool of Department of Periodontics, Thaimoogambigai Dental College and
      Hospital, Chennai. Thirty patients selected were grouped into two groups, Group-I
      consists of patients with generalized chronic periodontitis and on statin
      medication and Group-II consists of patients with generalized chronic
      periodontitis. Clinical parameters were recorded and gingival crevicular fluid
      (GCF) samples were analyzed for interleukin (IL)-1beta using commercially
      available enzyme-linked immunosorbent assay. RESULTS: The mean GCF IL-1beta
      levels in generalized chronic periodontitis patients who are on statin medication
      (Group-I) were lower than the generalized chronic periodontitis patients without
      statin medication (Group-II). CONCLUSION: Reduction of GCF IL-1beta levels in
      statin users indicate that statins have anti-inflammatory effect on periodontal
      disease.

PMID- 24014919
TI  - Unexpected death due to cefuroxime-induced disulfiram-like reaction.
AB  - Cefuoxime, a second-generation cephalosporin, is used in the treatment of Gram
      positive infections. Here, we report a case cefuroxime-induced disulfiram-like
      reaction which led to sudden death of the patient. 

PMID- 24014918
TI  - Antioxidative effects of hesperetin against lead acetate-induced oxidative stress
      in rats.
AB  - OBJECTIVES: Oxidative stress with subsequent lipid peroxidation (LP) has been
      suggested as a mechanism for lead-induced toxicity. The current study was carried
      out to evaluate antioxidant activity of hesperetin against lead acetate-induced
      oxidative stress. MATERIALS AND METHODS: The male rats were treated with
      hesperetin in combination with lead acetate (500 mg/L). RESULTS: The results
      indicated that hesperetin alone did not induce any significant changes in the
      biochemistry of serum, liver, and kidney tissues. On the other hand, lead-induced
      oxidative stress as indicated by significant changes in serum biochemical
      parameters, including increased lipid peroxide and decreased reduced glutathione
      (GSH), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase
      (GPx) levels in liver and kidney tissues. Hesperetin succeeded in improving these
      biochemical parameters towards the normal values of control. CONCLUSIONS: It
      suggests that hesperetin shows antioxidant activity and plays a protective role
      against lead-induced oxidative damage in liver and kidney of rats.

PMID- 24014920
TI  - Nevirapine-induced rash with eosinophilia and systemic symptoms (DRESS).
AB  - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an adverse
      reaction commonly occurring with antiepileptic agents. It was earlier referred to
      by various names such as dilantin hypersensitivity syndrome and anticonvulsant
      hypersensitivity syndrome. It is characterized by the triad of fever, skin
      eruption, and systemic involvement. DRESS syndrome has also been reported with a
      number of other drugs including allopurinol, minocycline, terbinafine,
      sulfonamides, azathioprine, dapsone, and antiretroviral agents such as abacavir
      and nevirapine. We describe a rare case of nevirapine-induced hypersensitivity
      syndrome that was successfully treated with oral steroids. 

PMID- 24014921
TI  - Terlipressin-induced hyponatremic seizure in a child.
AB  - Terlipressin, an analog of the natural hormone arginine-vasopressin, is a
      splanchnic constrictor that is used to control variceal bleeding in portal
      hypertension. It has a very good safety profile compared to vasopressin. Although
      rare, adverse effects such as hyponatremia and seizure can occur. We describe a 7
      year-old male child who developed hyponatremia induced by infusion of
      terlipressin which resulted in a generalized seizure. After withdrawal of
      terlipressin, the serum sodium level became normal. Through this case, we
      emphasize the importance of monitoring patient's electrolyte levels during the
      course of terlipressin therapy. 

PMID- 24014922
TI  - A case of thrombocytopenia caused by rifampicin and pyrazinamide.
AB  - A 32-year-old male patient was diagnosed as having pulmonary tuberculosis and put
      on category II antitubercular regime since he had a history of antituberculosis
      treatment 10 years ago. Within 3 weeks, patient presented with ulcers in mouth,
      and blood picture confirmed thrombocytopenia. Rifampicin-induced thrombocytopenia
      was suspected and antitubercular treatment stopped. Patient improved and was re
      exposed to the drugs one by one. After re-exposure with pyrazinamide, the
      platelet count decreased drastically and oral mucosal ecchymoses reappeared,
      while with rifampicin, thrombocytopenia was accompanied with petechiae on legs
      and forearms. Isoniazid, ethambutol, and streptomycin were continued.

PMID- 24014923
TI  - Severe photosensitivity reaction induced by topical diclofenac.
AB  - Albeit uncommon, photosensitivity reaction induced by diclofenac can be an
      unfortunate adverse reaction complicating its use as a topical analgesic. We here
      present a case of a patient who suffered such a reaction as a result of exposure
      to diclofenac, employed as a topical analgesic for low backache. The lesions
      healed with conservative management without extensive scarring or other
      complications. 

PMID- 24014924
TI  - Inflamed psoriatic plaques: drug toxicity or disease exacerbation?
AB  - We are presenting a case of Methotrexate treated stable plaque psoriasis, in whom
      inflamed psoriatic plaques of drug toxicity were misdiagnosed as disease
      exacerbation. Erosive psoriatic plaques were present in the absence of
      biochemical or hematological derangements. Ulceration of psoriatic plaques in the
      presence of disturbed hematological profile is well described as a harbinger of
      methotrexate toxicity, but this kind of erosions in the absence of any systemic
      involvement is the first report of its kind.

PMID- 24014925
TI  - Integration can lead to efficiencies as well as costs.

PMID- 24014926
TI  - Chronic fluoxetine treatment and sexual behavior in male and female albino rats.

PMID- 24014927
TI  - Detection of complete dihydropyrimidine dehydrogenase deficiency in a Tunisian
      family using a simple phenotypic test.

PMID- 24014928
TI  - Rutin exerts antiulcer effect by inhibiting the gastric proton pump.

PMID- 24014929
TI  - Effects of Withania somnifera in patients of schizophrenia: a randomized, double
      blind, placebo controlled pilot trial study.

PMID- 24014930
TI  - Bayesian Frequentist hybrid Model wth Application to the Analysis of Gene Copy
      Number Changes.
AB  - Gene copy number (GCN) changes are common characteristics of many genetic
      diseases. Comparative genomic hybridization (CGH) is a new technology widely used
      today to screen the GCN changes in mutant cells with high resolution genome-wide.
      Statistical methods for analyzing such CGH data have been evolving. Existing
      methods are either frequentist's, or full Bayesian. The former often has
      computational advantage, while the latter can incorporate prior information into
      the model, but could be misleading when one does not have sound prior
      information. In an attempt to take full advantages of both approaches, we develop
      a Bayesian-frequentist hybrid approach, in which a subset of the model parameters
      is inferred by the Bayesian method, while the rest parameters by the
      frequentist's. This new hybrid approach provides advantages over those of the
      Bayesian or frequentist's method used alone. This is especially the case when
      sound prior information is available on part of the parameters, and the sample
      size is relatively small. Spatial dependence and false discovery rate are also
      discussed, and the parameter estimation is efficient. As an illustration, we used
      the proposed hybrid approach to analyze a real CGH data.

PMID- 24014931
TI  - Selective hydride generation- cryotrapping- ICP-MS for arsenic speciation
      analysis at picogram levels: analysis of river and sea water reference materials
      and human bladder epithelial cells.
AB  - An ultra sensitive method for arsenic (As) speciation analysis based on selective
      hydride generation (HG) with preconcentration by cryotrapping (CT) and
      inductively coupled plasma- mass spectrometry (ICP-MS) detection is presented.
      Determination of valence of the As species is performed by selective HG without
      prereduction (trivalent species only) or with L-cysteine prereduction (sum of tri
      and pentavalent species). Methylated species are resolved on the basis of
      thermal desorption of formed methyl substituted arsines after collection at -196
      degrees C. Limits of detection of 3.4, 0.04, 0.14 and 0.10 pg mL-1 (ppt) were
      achieved for inorganic As, mono-, di- and trimethylated species, respectively,
      from a 500 MUL sample. Speciation analysis of river water (NRC SLRS-4 and SLRS-5)
      and sea water (NRC CASS-4, CASS-5 and NASS-5) reference materials certified to
      contain 0.4 to 1.3 ng mL-1 total As was performed. The concentrations of
      methylated As species in tens of pg mL-1 range obtained by HG-CT-ICP-MS systems
      in three laboratories were in excellent agreement and compared well with results
      of HG-CT-atomic absorption spectrometry and anion exchange liquid chromatography-
      ICP-MS; sums of detected species agreed well with the certified total As content.
      HG-CT-ICP-MS method was successfully used for analysis of microsamples of
      exfoliated bladder epithelial cells isolated from human urine. Here, samples of
      lysates of 25 to 550 thousand cells contained typically tens pg up to ng of iAs
      species and from single to hundreds pg of methylated species, well within
      detection power of the presented method. A significant portion of As in the cells
      was found in the form of the highly toxic trivalent species.

PMID- 24014932
TI  - Does weight affect children's test scores and teacher assessments differently?
AB  - The prevalence of childhood overweight and obesity increased dramatically in the
      United States during the past three decades. This increase has adverse public
      health implications, but its implication for children's academic outcomes is less
      clear. This paper uses data from five waves of the Early Childhood Longitudinal
      Study-Kindergarten to examine how children's weight is related to their scores on
      standardized tests and to their teachers' assessments of their academic ability.
      The results indicate that children's weight is more negatively related to teacher
      assessments of their academic performance than to test scores.

PMID- 24014933
TI  - Statistical properties on semiparametric regression for evaluating pathway
      effects.
AB  - Most statistical methods for microarray data analysis consider one gene at a
      time, and they may miss subtle changes at the single gene level. This limitation
      may be overcome by considering a set of genes simultaneously where the gene sets
      are derived from prior biological knowledge. We call a pathway as a predefined
      set of genes that serve a particular cellular or physiological function. Limited
      work has been done in the regression settings to study the effects of clinical
      covariates and expression levels of genes in a pathway on a continuous clinical
      outcome. A semiparametric regression approach for identifying pathways related to
      a continuous outcome was proposed by Liu et al. (2007), who demonstrated the
      connection between a least squares kernel machine for nonparametric pathway
      effect and a restricted maximum likelihood (REML) for variance components.
      However, the asymptotic properties on a semiparametric regression for identifying
      pathway have never been studied. In this paper, we study the asymptotic
      properties of the parameter estimates on semiparametric regression and compare
      Liu et al.'s REML with our REML obtained from a profile likelihood. We prove that
      both approaches provide consistent estimators, have [Formula: see text]
      convergence rate under regularity conditions, and have either an asymptotically
      normal distribution or a mixture of normal distributions. However, the estimators
      based on our REML obtained from a profile likelihood have a theoretically smaller
      mean squared error than those of Liu et al.'s REML. Simulation study supports
      this theoretical result. A profile restricted likelihood ratio test is also
      provided for the non-standard testing problem. We apply our approach to a type II
      diabetes data set (Mootha et al., 2003).

PMID- 24014934
TI  - What happened (and what didn't): Discourse constraints on encoding of plausible
      alternatives.
AB  - Three experiments investigated how font emphasis influences reading and
      remembering discourse. Although past work suggests that contrastive pitch
      contours benefit memory by promoting encoding of salient alternatives, it is
      unclear both whether this effect generalizes to other forms of linguistic
      prominence and how the set of alternatives is constrained. Participants read
      discourses in which some true propositions had salient alternatives (e.g.,
      British scientists found the endangered monkey when the discourse also mentioned
      French scientists) and completed a recognition memory test. In Experiments 1 and
      2, font emphasis in the initial presentation increased participants' ability to
      later reject false statements about salient alternatives but not about
      unmentioned items (e.g., Portuguese scientists). In Experiment 3, font emphasis
      helped reject false statements about plausible alternatives, but not about less
      plausible alternatives that were nevertheless established in the discourse. These
      results suggest readers encode a narrow set of only those alternatives plausible
      in the particular discourse. They also indicate that multiple manipulations of
      linguistic prominence, not just prosody, can lead to consideration of
      alternatives.

PMID- 24014935
TI  - Limitations on adaptation to foreign accents.
AB  - Although foreign accents can be highly dissimilar to native speech, existing
      research suggests that listeners readily adapt to foreign accents after minimal
      exposure. However, listeners often report difficulty understanding non-native
      accents, and the time-course and specificity of adaptation remain unclear. Across
      five experiments, we examined whether listeners could use a newly learned feature
      of a foreign accent to eliminate lexical competitors during online speech
      perception. Participants heard the speech of a native English speaker and a
      native speaker of Quebec French who, in English, pronounces /i/ as [i] (e.g.,
      weak as wick) before all consonants except voiced fricatives. We examined whether
      listeners could learn to eliminate a shifted /i/-competitor (e.g., weak) when
      interpreting the accented talker produce an unshifted word (e.g., wheeze). In
      four experiments, adaptation was strikingly limited, though improvement across
      the course of the experiment and with stimulus variations indicates learning was
      possible. In a fifth experiment, adaptation was not improved when a native
      English talker produced the critical vowel shift, demonstrating that the
      limitation is not simply due to the fact the accented talker was non-native.
      These findings suggest that although listeners can arrive at the correct
      interpretation of a foreign accent, this process can pose significant difficulty.

PMID- 24014936
TI  - Molecular organization of 'Rh' gene is likely to be heterogeneous across the
      world.

PMID- 24014937
TI  - Acute non-immunologic hemolytic transfusion reaction due to intravenous dextrose
      infusion.

PMID- 24014938
TI  - Implementing fourth generation human immunodeficiency virus enzyme-linked
      immunosorbent assay: One step forward in blood safety.

PMID- 24014939
TI  - Retrospective evaluation of adverse transfusion reactions following blood product
      transfusion from a tertiary care hospital: A preliminary step towards
      hemovigilance.
AB  - BACKGROUND: The goal of hemovigilance is to increase the safety and quality of
      blood transfusion. Identification of the adverse reactions will help in taking
      appropriate steps to reduce their incidence and make blood transfusion process as
      safe as possible. AIMS: To determine the frequency and type of transfusion
      reactions (TRs) occurring in patients, reported to the blood bank at our
      institute. MATERIALS AND METHODS: A retrospective review of all TRs reported to
      the blood bank at the All India Institute of Medical Sciences, between December
      2007 and April 2012 was done. All the TRs were evaluated in the blood bank and
      classified using standard definitions. RESULTS: During the study period a total
      of 380,658 bloods and blood components were issued by our blood bank. Out of the
      total 196 adverse reactions reported under the hemovigilance system, the most
      common type of reaction observed was allergic 55.1% (n = 108), followed by
      febrile non-hemolytic transfusion reaction (FNHTR) 35.7% (n = 70). Other less
      frequently observed reactions were Anaphylactoid reactions 5.1% (n = 10), Acute
      non-immune HTRs 2.6% (n = 5), Circulatory overload 0.5% (n = 1), Transfusion
      related acute lung injury 0.5% (n = 1), Delayed HTRs 0.5% (n = 1). Not a single
      case of bacterial contamination was observed. CONCLUSION: The frequency of TRs in
      our patients was found to be 0.05% (196 out of 380,658). This can be an
      underestimation of the true incidence because of under reporting. It should be
      the responsibility of the blood transfusion consultant to create awareness
      amongst their clinical counterpart about safe transfusion practices so that
      proper hemovigilance system can be achieved to provide better patient care.

PMID- 24014940
TI  - Transfusion transmittable infections - Seroprevalence among blood donors in a
      tertiary care hospital of Delhi.
AB  - CONTEXT: Transfusion transmittable infections (TTI) continue to be a major threat
      to safe transfusion practices. Blood is one of the major sources of transmission
      of infectious diseases viz. human immunodeficiency virus (HIV), hepatitis B virus
      (HBV), hepatitis C virus (HCV), syphilis, malaria, and many other infections in
      India. Screening assays for the infectious diseases with excellent sensitivity
      and specificity helps to enhance the safety of the blood transfusions reducing
      the diagnostic window period as much as possible. AIMS: The present study was
      designed to determine the seroprevalence of TTIs viz., HIV, HCV, and HBV, among
      the blood donors in Max Super Specialty Hospital, New Delhi, India based on dual
      testing strategy using high sensitive screening assays such as enhanced
      chemiluminescence assay and nucleic acid testing (NAT). MATERIALS AND METHODS: A
      total of 41207 blood units collected from the donors (both voluntary and
      replacement donors) were screened for the TTI s, viz., anti HIV 1 and 2 antibody,
      anti HCV antibody, anti HBcore antibody, and HBsAg by enhanced chemiluminescence
      assay on VITROS((r)) ECiQ immunodiagnostics system. NAT was performed using Roche
      Cobas((r)) TaqScreen MPX assay, which can detect simultaneously HIV 1 (groups M
      and O), HIV-2, HCV, and HBV on Roche Cobas((r)) s201 system. RESULTS: The
      seroprevalence of HIV, HBsAg, anti HBcore antibody, and HCV based on enhanced
      chemiluminescence assay was found to be 0.25, 0.2, 7.06, and 0.7%, respectively.
      A total number of 6587 samples from July 2010 to December 2010 were tested on
      NAT, of which 3 samples were reactive for HBV in NAT; this was missed by enhanced
      chemiluminescence assay. CONCLUSIONS: Based on the seroprevalence study of
      infectious diseases viz., HIV, HBV, and HCV, we conclude that screening of blood
      and blood components by dual testing strategy using high sensitivity serological
      assay like enhanced chemiluminescence technology and NAT helps in detecting the
      potentially infectious blood units in all phases of infection, which aids in
      enhancing the safety of blood transfusion and reducing the potential risk of post
      transfusion infection.

PMID- 24014941
TI  - RHD alleles in the Tunisian population.
AB  - BACKGROUND: A comprehensive survey of RHD alleles in Tunisia population was
      lacking. The aim of this study was to use a multiplex RHD typing assay for
      simultaneous detection of partial D especially with RHD/RHCE deoxyribonucleic
      acid (DNA) sequence exchange mechanism and some weak D alleles. MATERIALS AND
      METHODS: Six RHD specific primer sets were designed to amplify RHD exons 3, 4, 5,
      6, 7 and 9. DNA from 2000 blood donors (1777 D+ and 223 D-) from several regions
      was selected for RHD genotyping using a PCR multiplex assay. Further molecular
      investigations were done to characterize the RHD variants that were identified by
      the PCR multiplex assay. RESULTS: In the 1777 D+ samples, only 10 individuals
      showed the absence of amplification of exons 4 and 5 that were subsequently
      identified by PCR-SSP as weak D type 4 variants. No hybrid allele was detected.
      In the 223 D-, RHD amplification of some exons was observed only in 5 samples: 4
      individuals expressed only RHD exon 9, and one subject lacking exons 4 and 5.
      These samples were then screened by PCR-SSPs on d(C) ce(s) and weak D type 4,
      respectively. CONCLUSION: The weak D type 4 appears to be the most common D
      variant allele. We have not found any partial D variant. Findings also indicated
      that RHD gene deletion is the most prevalent cause of the D- phenotype in the
      Tunisian population.

PMID- 24014942
TI  - Seroprevalence of human immunodeficiency virus in north Indian blood donors using
      third and fourth generation Enzyme linked immunosorbent assay.
AB  - BACKGROUND: The percentage of HIV cases attributable to blood transfusion has
      decreased significantly in the last decade. The newer 4(th) generation Enzyme
      linked immunosorbent assay (ELISA) has been shown to have increased sensitivity
      compared to 3(rd) generation ELISA. OBJECTIVES: To estimate the seroprevalence of
      HIV among blood donors using 4(th) generation ELISA assay and to compare it with
      the 3(rd) generation ELISA. MATERIALS AND METHODS: This prospective study
      involved 10,200 blood donors- 6,800 were voluntary donors (3400-students and 3400
      non students) and 3400 were replacement donors. All blood units were tested with
      3(rd) as well as 4(th) generation ELISA. All samples found reactive or in grey
      zone with either 3(rd) or 4(th) generation ELISA were retested by Western blot
      (WB). RESULTS: The seroprevalence of HIV was estimated to be 1.37/1000 donations
      (0.14%) with 3(rd) generation ELISA compared to 3.62/1000 donations (0.36%) with
      4(th) generation ELISA (p>0.05). The seroprevalence of HIV among voluntary donors
      was estimated to be 1.32/1000 donations (0.13%) with 3(rd) generation ELISA and
      3.67/1000 donations (0.36%) with 4(th) generation ELISA. The prevalence of HIV
      among replacement donors was 1.47/1000 donations (0.15%) with 3(rd) generation
      ELISA and 3.52/1000 donations (0.35%) with 4(th) generation ELISA. CONCLUSION:
      4(th) generation HIV ELISA detects a higher number of seroreactive donors
      compared to 3(rd) generation ELISA. However, larger studies are required with
      confirmatory tests for both 3(rd) and 4(th) generation ELISA for making any
      policy changes.

PMID- 24014943
TI  - Looking to the future, working on the present. Intention to donate blood and risk
      behavior: A study on adolescents.
AB  - BACKGROUND: The aim of this work was to investigate adolescents' propensity to
      donate blood, the incidence in this population of risk behaviors that limit and
      restrict the potential for blood donation, thus reducing the number of possible
      subjects suitable for donation, and the link between propensity to donate and
      healthy lifestyles. MATERIALS AND METHODS: Adolescents were asked to complete an
      anonymous self-report questionnaire during class time. The questionnaire included
      ad hoc items designed to investigate the intention to donate blood and behaviors
      traditionally considered to put adolescents' "health at risk". Participants were
      201 students from northern Italy (range 12-19, M = 17.98, SD = 1.82; 38.9% male,
      61.1% female). RESULTS: About half of respondents perceived that they were able
      to donate blood and could overcome any obstacle that might prevent them from
      doing so. Some of the examined risk behaviors were widespread in the population
      under consideration. The linear regressions run show that there is no link
      between the propensity to give blood and a tendency to engage in healthy
      lifestyles. CONCLUSION: The study shows that adolescents demonstrate an interest
      in blood donation; however, it shows a real lack of "action" to make it happen:
      there is, indeed, a serious lack of attention to matters related to healthy
      lifestyles. In fact, adolescents are not aware of how to act to access the world
      of donation, with the risk that they present themselves at blood donation centers
      and are then found to be unfit to donate. The research offers many suggestions
      and implications.

PMID- 24014944
TI  - Detection of alloimmunization to ensure safer transfusion practice.
AB  - BACKGROUND: Serological safety is an integral part of overall safety for blood
      banks. Emphasis is on the use of routinue Red Blood Cell (RBC) antibody screen
      test, at set time intervals, to reduce risks related to alloantibodies. Also
      emphasis is on importance of issuing antigen negative blood to alloantibody
      positive patients. Effect of using leucodepleted blood on the rate of
      alloimmunization is highlighted. The concept of provision of phenotypically
      matched blood is suggested. MATERIALS AND METHODS: Antibody screen test is
      important to select appropriate blood for transfusion. Repeat antibody screen
      testing, except if time interval between the earlier and subsequent transfusion
      was less than 72 hours, followed by antibody identification, if required, was
      performed in patients being treated with repeat multiple blood transfusions.
      Between February 2008 and June 2009, repeat samples of 306 multi-transfused
      patients were analyzed. Search for irregular antibodies and reading of results
      was conducted using RBC panels (three-cell panel of Column Agglutination
      Technology (CAT) and two cell panel of the Solid Phase Red Cell Adherence
      Technology (SPRCAT). Specificities of antibodies were investigated using
      appropriate panels, 11 cell panel of CAT and 16 cell panel of SPRCA. These
      technologies, detecting agglutination in columns and reactions in solid phase,
      evaluate the attachment of irregular incomplete antibody to antigen in the first
      phase of immunological reaction more directly and hence improve the reading of
      agglutination. Three to four log leuco reduced red blood cells were transfused to
      patients in the study using blood collection bags with integral filters. RESULTS:
      Alloimmunization rate of 4.24% was detected from 306 multiply transfused patients
      tested and followed up. The Transfusion therapy may become significantly
      complicated. CONCLUSION: Red cell antibody screening and identification and
      subsequent issue of antigen negative blood have a significant role in improving
      blood safety. Centers that have incorporated antibody screen test and
      identification have ensured safe transfusion. Identified patients should be
      flagged in a database and information shared. Such patients can be given carry-on
      cards and educated about the names of the identified antibodies. Full red cell
      phenotyping of individuals, patients and donors, can be feasibility.

PMID- 24014945
TI  - Preoperative predictors of blood component transfusion in living donor liver
      transplantation.
AB  - CONTEXT: Extensive bleeding associated with liver transplantation is a major
      challenge faced by transplant surgeons, worldwide. AIMS: To evaluate the blood
      component consumption and determine preoperative factors that predict the same in
      living donor liver transplantation (LDLT). SETTINGS AND DESIGN: This prospective
      study was performed for a 1 year period, from March 2010 to February 2011.
      MATERIALS AND METHODS: Intra- and postoperative utilization of blood components
      in 152 patients undergoing LDLT was evaluated and preoperative patient parameters
      like age, gender, height, weight, disease etiology, hemoglobin (Hb), hematocrit
      (Hct), platelet count (Plt), total leukocyte count (TLC), activated partial
      thromboplastin time (aPTT), international normalized ratio (INR), serum bilirubin
      (T. bilirubin), total proteins (T. proteins), albumin to globulin ratio (A/G
      ratio), serum creatinine (S. creatinine), blood urea (B. urea), and serum
      electrolytes were assessed to determine their predictive values. Univariate and
      stepwise discriminant analysis identified those factors, which could predict the
      consumption of each blood component. RESULTS: The average utilization of packed
      red cells (PRCs), cryoprecipitates (cryo), apheresis platelets, and fresh frozen
      plasma was 8.48 units, 2.19 units, 0.93 units, and 2,025 ml, respectively.
      Disease etiology and blood component consumption were significantly correlated.
      Separate prediction models which could predict consumption of each blood
      component in intra and postoperative phase of LDLT were derived from among the
      preoperative Hb, Hct, model for end-stage liver disease (MELD) score, body
      surface area (BSA), Plt, T. proteins, S. creatinine, B. urea, INR, and serum
      sodium and chloride. CONCLUSIONS: Preoperative variables can effectively predict
      the blood component requirements during liver transplantation, thereby allowing
      blood transfusion services in being better prepared for surgical procedure.

PMID- 24014946
TI  - Interesting case of G6PD deficiency anemia with severe hemolysis.
AB  - Severe hemolysis was observed in a critically ill patient with G6Pd deficiency
      where the causative trigger could not be identified. We describe one young
      patient with severe hemolysis treated with two cycles of plasmapheresis which
      proved to be an effective tool in the treatment. The patient presented with
      diffuse pain abdomen, vomiting, yellowish discoloration of sclera and skin and
      acute breathlessness. Hemoglobin 5.4 mg/dl and total (T) serum bilirubin 17.08
      mg/dl: Direct (D) 4.10 mg/dl and Indirect (I) 12.98 mg/dl. Subsequently patient
      started passing black color urine. As the patient developed severe hemolysis and
      the trigger agent of hemolysis was unknown, two cycles of plasmapheresis were
      performed with the aim to remove unknown causative agent. Consequently no trace
      of hemolysis was found and patient stabilized. Plasmapheresis can be used to
      treat G6PD deficient patients with severe hemolysis due to unidentified trigger
      agent. 

PMID- 24014947
TI  - Delayed hemolytic transfusion reaction with multiple alloantibody (Anti S, N, K)
      and a monospecific autoanti-JK(b) in intermediate beta-thalassemia patient in
      Tabriz.
AB  - It appears that delayed hemolytic transfusion reactions may occur several days
      after the administration of donor red cells is true even though they have been
      shown to be compatible in cross match tests by the antiglobulin technique. A
      specific case was observed in our center, which confirms the fact. The patient
      was a 37-year-old male suffering from intermediate beta-thalassemia. He had a
      history of two previous transfusions, with unknown transfusion reaction. In the
      last transfusion, laboratory data showed: Hb 7.8 g/dL and Hematocrit (Hct) 24.2%.
      The patient received two units of cross matched, compatible concentrated red
      blood cells (RBCs). After eight days a severe reaction was observed with clinical
      evidence of tachycardia, fatigue, fever, back pain, chest discomfort, jaundice,
      nausea and anorexia. Accordingly delayed hemolytic transfusion reaction was
      suspected, and anti-RBC antibodies were tested. Laboratory tests revealed the
      presence of three alloantibodies: Anti-N, anti-S, anti-K, and a monospecific
      autoanti-JK(b). 

PMID- 24014948
TI  - Autoimmune hemolytic anemia in a patient with Malaria.
AB  - Autoimmune Hemolytic Anemia (AIHA), a very infrequent condition which represents
      a group of disorders in which presence of autoantibodies directed against self
      antigens leads to shortened red cell survival. Till date, a very few cases of
      AIHA in Malaria patients are reported worldwide but still AIHA should be
      considered a relatively rare cause of anemia in malaria. A 20 year male presented
      with intermittent fever since seven days and yellowish discoloration of urine and
      sclera since 5 days. He was transfused three units of blood at a private clinic
      before one month. On examination, pallor, icterus and spelnomegaly were present.
      Hemoglobin (Hb) was 3.2 gm% and peripheral smear revealed ring forms of both
      Plasmodium vivax and Plasmodium falciparum. Serum LDH and Serum billirubin
      (Indirect and Direct) were high. This patient's blood group was B +ve with
      positive autocontrol. Indirect Antiglobulin Test (IAT), antibody screening and
      antibody identification were pan-positive with reaction strength of +4 against
      each cell. Direct Antiglobulin Test was +4 positive anti IgG and negative with
      anti C3. He was treated with Artesunate and methylprednisone. Least incompatible,
      saline washed O Neg and B neg red cells were transfused on the 2(nd) day of
      starting treatment. Hb was raised to 6.1 gm% on 4(th) day. Patient was discharged
      on 9th day with Hb 7.0 gm% with oral tapering dose of steroids. In the above
      case, patient was suffering from high grade malarial parasitemia with co-existing
      autoimmune RBC destruction by IgG auto-antibodies which led to sudden drop in Hb
      and rise in serum LDH and indirect billirubin. Least incompatible packed red
      cells along with antimalarials and steroids led to clinical improvement. So far,
      one case report each from India, Korea, Canada and Germany and one case series
      report of three cases from India have been reported. Under-reporting or rarity of
      this phenomenon may be accountable for this. 

PMID- 24014949
TI  - A rare case of haemolytic disease of newborn with Bombay phenotype mother.
AB  - We are reporting a rare case of severe hemolytic disease of newborn (HDN) with
      Bombay phenotype mother. A retrospective study of a case with severe haemolytic
      disease of newborn with Bombay phenotype mother was done. Blood grouping,
      antibody screening, and lectin study was done on the blood sample of the baby and
      mother to confirm the diagnosis. Hematological and biochemical parameters were
      obtained from the hospital laboratory information system for the analysis. Blood
      group of the baby was A positive, direct antiglobulin test was negative. Blood
      group of the mother was confirmed to be Bombay phenotype, Hematological
      parameters showed all the signs of ongoing hemolysis and the bilirubin level was
      in the zone of exchange transfusion. Due to the unavailability of this rare
      phenotype blood unit, baby was managed conservatively. Anticipating the fetal
      anemia and HDN with mothers having Bombay phenotype and prior notification to the
      transfusion services will be of great help in optimizing the neonatal care and
      outcome. 

PMID- 24014951
TI  - Perspectives and attitudes to voluntary blood donation in a tertiary referral
      hospital blood bank.

PMID- 24014950
TI  - Rhesus-D zygosity and hemolytic disease of fetus and newborn.
AB  - Alloimmunization against the Rhesus-D (RhD) antigen still remains as a major
      cause of hemolytic disease of fetus and newborn (HDFN). Determination of paternal
      RhDzygosity is performed by molecular testing and is valuable for the management
      of alloimmunized pregnant women. A 30-year-old pregnant woman with AB negative
      blood group presented with two consecutive abortions and no history of blood
      transfusion. By application of the antibody screening, identification panel, and
      selected cells, she was found to be highly alloimmunized. RhDzygosity was
      performed on her partner and was shown to be homozygous for RhD. The sequence-
      specific priming-polymerase chain reaction used in this report is essential to
      establish whether the mother requires an appropriate immunoprophylaxis or the
      fetus is at risk of HDFN. 

PMID- 24014952
TI  - Prevalence of ABO blood groups and rhesus (Rh) factor in the population residing
      in and around Amritsar, Punjab (a 4-year study from June 2007 to June 2011).

PMID- 24014953
TI  - Hepatitis B virus vaccination of voluntary blood donors and immunization status
      assessment by Anti-Hepatitis B Surface (HBs) antibody titer.

PMID- 24014954
TI  - Analysis of blood donor deferral pattern: Scenario in a Tertiary Health Care
      Hospital in India.

PMID- 24014955
TI  - A profile of rare bloods in Oman.

PMID- 24014956
TI  - Seroprevalence of human immunodeficiency virus, hepatitis B virus and hepatits C
      virus in blood donors of Jammu Province: A tertiary care centre experience.

PMID- 24014957
TI  - Profile of deferral of blood donors in regional blood transfusion center in North
      India.

PMID- 24014958
TI  - Needs assessment and evaluation are vital components in curriculum design.

PMID- 24014959
TI  - Promoting affordable and quality tuberculosis testing in India.

PMID- 24014960
TI  - Multidrug resistance in bacteria: a serious patient safety challenge for India.
AB  - Patient safety is an important issue affecting the delivery of health care in
      developed, transitional and developing countries. With the advancements in
      patient care, hitherto unknown issues relating to patient safety are emerging. An
      important problem endangering patient safety is infections acquired in the health
      care facilities. Health care associated infections (HCAIs) are no longer a local
      or regional problem. With the dissemination of multi-drug resistant bacteria
      across the globe, the problem of HCAIs has become even grimmer. The emergence of
      pan-resistant bacterial strains, compounded by lack of availability of new
      antimicrobials foretells a grave future for management of infections acquired in
      hospitals. Therefore, it is important to frame local policies and measures and
      take affirmative actions for prevention of HCAIs and reduce the burden of multi
      drug resistance. 

PMID- 24014961
TI  - Diagnostic performance of commercially available enzyme-linked immunosorbent
      assay kit in the diagnosis of extrapulmonary tuberculosis.
AB  - OBJECTIVES: Antibody based serodiagnosis tests for tuberculosis (TB) was used
      widely in developed and developing countries. Pathozyme Myco((r)) immunoglobulin
      (Ig) M, IgA, and IgG were evaluated in pulmonary TB in many studies. MATERIALS
      AND METHODS: In this study we assessed this commercially available kit in
      detecting extrapulmonary TB (EPTB). RESULTS: A total of 354 subjects were
      recruited for the study, of which 217 (61.2%) were EPTB patients and 137 (38.7%)
      were subjects with no suggestive TB. The mean age was 29.7 +/- 13.7 and 31.2 +/-
      15.2 years, respectively for two groups. Serum samples were tested for IgM, IgA,
      and IgG using Pathozyme Myco((r)) IgM, IgA, and IgG kit. The individual
      specificity rates of IgM, IgA, and IgG were 70.8% (95% confidence interval (CI):
      62.7-77.7), 77.3% (95% CI: 68.6-83.5), and 68.6%. (95% CI: 60.4-75.7); while
      their sensitivity was 29% (95% CI: 23.4-35.4), 24.4% (95% CI: 19.1-30.5), and
      34.5% (95% CI: 28.5-41.1); respectively. CONCLUSION: The serological tests either
      singly or in combination failed or performed poorly to diagnose EPTB.

PMID- 24014962
TI  - Effect of urogenital cleaning with paper soap on bacterial contamination rate
      while collecting midstream urine specimens.
AB  - CONTEXT: Urinary tract infection (UTI) is one of the major health problems. Urine
      culture is considered as a gold standard method for the diagnosis of UTI. But,
      improper sample collection can lead to contamination with normal urogenital
      flora. Use of any portable disinfectant that can reduce contamination rate would
      be the significant help in urine culture interpretation. AIMS: To observe the
      effect of urogenital cleaning with paper soap on bacterial contamination rate
      while collecting specimens. MATERIALS AND METHODS: A cross-sectional comparative
      study was done in 600 patients aged 15-45 years, equally divided into three
      groups. The first group was given sterile container and instructed to collect
      midstream clean catch urine (MSU) after urogenital cleaning with provided piece
      of paper soap. The second group was given sterile container and strictly
      instructed to collect the MSU sample after urogenital cleansing by tap water
      only. The third group was given the sterile container and asked for midstream
      urine. Collected specimens were inoculated in CLED media, incubated aerobically
      for overnight at 37 degrees C. Reporting of culture was done according to the
      guideline of American Society of Microbiology. RESULTS: The contamination rate in
      the three groups were 6.0%, 13.0%, and 27.5%, respectively (P value < 0.05),
      which was statistically significant. CONCLUSIONS: Contamination rate was
      significantly lower in group who provided urine specimen after urogenital
      cleaning with paper soap. Thus, cleaning the urogenital area may reduce the need
      of the repeat sample to rule out actual contamination and prevent from the
      unnecessary antibiotic treatment.

PMID- 24014963
TI  - Detection of Different beta-Lactamases and their Co-existence by Using Various
      Discs Combination Methods in Clinical Isolates of Enterobacteriaceae and
      Pseudomonas spp.
AB  - BACKGROUND: Resistance to broad spectrum beta-lactams mediated by extended
      spectrum beta-lactamase (ESBL), AmpC, and metallobetalactamase (MBLs) enzymes are
      an increasing problem worldwide. The study was aimed to detect occurrence rate
      and to evaluate different substrates and inhibitors by disc combination method
      for detecting varying degree of beta-lactamase enzymes and their co-production.
      MATERIALS AND METHODS: A disc panel containing imipenem (IMP), IMP/EDTA,
      ceftazidime (CA), ceftazidime-tazobactum (CAT), CAT/cloxacillin (CLOX),
      ceftazidime-clavulanic acid (CAC), CAC/CLOX, cefoxitin (CN), and CN/CLOX in a
      single plate was used to detect presence of ESBLs, AmpC, and MBLs and/or their co
      existence in 184 consecutive, nonrepetitive, clinical isolates of
      Enterobacteriace (n = 96) and Pseudomonas spp. (n = 88) from pus samples of
      hospitalized patients, resistant to 3(rd) generation cephalosporins. RESULTS: Out
      of a total of 96 clinical isolates of Enterobacteriaceae, 18.7, 20.8, and 27%
      were pure ESBL, AmpC, and MBL producers, respectively. ESBL and AmpC were co
      produced by 25% isolates. Among 88 Pseudomonas spp. 38.6, 13, and 6% were pure
      MBL, ESBL, and AmpC producers, respectively. ESBL/AmpC and MBL/AmpC co-production
      was seen in 20% and 18% isolates, respectively. Among ESBL and AmpC co-producers,
      CA/CAC/CLOX disc combination (DC) missed 7 of the 24 ESBL producers in
      Enterobacteriace and 4 of the 18 ESBL in Pseudomonas spp., which were detected by
      CA/CAT/CLOX DC. No mechanism was detected among 8.3% Enterobacteriaceae and 2.3%
      Pseudomonas isolates. CONCLUSION: Diagnostic problems posed by co-existence of
      different classes of beta-lactamases in a single isolate could be solved by disc
      combination method by using simple panel of discs containing CA, CAT, CAT/CLOX,
      IMP, and IMP/EDTA.

PMID- 24014964
TI  - Thyroid hormone levels in apparently euthyroid subjects with essential
      hypertension in a tertiary hospital in Nigeria.
AB  - BACKGROUND: High blood pressure (BP) is a major health problem in Nigeria and the
      involvement of thyroid hormones in this condition has not been evaluated in this
      center. OBJECTIVE: The objective of this study was to evaluate the proportion of
      patients with an essential hypertension who had abnormal thyroid hormone levels
      and the type of thyroid disorders commonly observed in this group of patients.
      MATERIALS AND METHODS: A retrospective study of 94 patients (30 males, aged 30.4
      +/- 2 years and 64 females, aged 43.4 +/- 1.3 years) with essential hypertension
      was carried out between January 2005 and December 2007. Demographic and other
      medical information were obtained from the health records. Analysis of laboratory
      results of triiodothyronine (T3), Thyroxine (T4), and thyroid stimulating hormone
      (TSH) were made. RESULTS: Of the 94 patients evaluated, 26 (27.7%) had abnormal
      thyroid hormone levels, with 23.4% having hyperthyroidism, 4.3% had sub-clinical
      hypothyroidism and none had overt hypothyroidism. Of the 26 subjects with
      abnormal thyroid hormone levels, 18 (69.2%) were females while 8 (30.8%) were
      males. Out of the 18 female subjects with abnormal thyroid hormone levels, 16 had
      hyperthyroid levels while 2 had sub-clinical hypothyroid levels. Out of the 8
      male patients, 6 had hyperthyroid hormone levels while 2 had sub-clinical
      hypothyroid levels. CONCLUSION: Thyroid hormone abnormalities are common in
      patients with essential hypertension. Hyperthyroidism was the most common thyroid
      disorder observed. Young patients presenting with essential hypertension should
      be screened for thyroid hormone abnormalities since they can best be managed by
      treating the underlying causes.

PMID- 24014965
TI  - Evaluation of serum zinc status and glycated hemoglobin of type 2 diabetes
      mellitus patients in a tertiary care hospital of assam.
AB  - The present study was undertaken to find out any correlation between serum zinc
      concentration and HbA1C% in patients with type 2 diabetes mellitus (DM). The
      study was carried out on 50 newly diagnosed patients of type 2 diabetes and
      controls in the Department of Biochemistry, Assam Medical College and Hospital,
      Dibrugarh. Analyses of blood glucose (fasting and postprandial), glycated
      hemoglobin (HbA1c), serum zinc, urea, and creatinine concentrations were
      performed by standard methods. Concentrations of fasting and postprandial blood
      glucose were significantly higher in the diabetic group than controls (P < 0.001)
      and the mean HbA1c% was also higher in cases (8.32% +/-1.58%). The mean serum
      zinc concentration in cases was found to be significantly lower than controls
      (79.85 +/- 13.4 vs. 109.74 +/- 9.72 MUg/dL) and P < 0.001 with correlation
      coefficient r = -0.804. Present study revealed an inverse relationship between
      HbA1C% and serum zinc concentration in patients with type 2 DM, substantiated by
      regression analysis. 

PMID- 24014966
TI  - Association of hematological profile of human immunodeficiency virus-positive
      patients with clinicoimmunologic stages of the disease.
AB  - AIM: This work was carried out to study the hematologic profile of human
      immunodeficiency virus (HIV)-positive patients and its association with the
      clinicoimmunologic stage of the disease. MATERIALS AND METHODS: A total of 187
      patients with HIV, whether symptomatic or asymptomatic, diagnosed by enzyme
      linked immunosorbent assay (ELISA) method according to the National AIDS Control
      Organization (NACO) guidelines were included in this study. Patients in the study
      population were divided into two groups: (1) Group A (antiretroviral therapy
      (ART) included patients receiving ART [ART-Y]) and (2) Group B included treatment
      naive patients (ART-N). The patients were tested for hemoglobin (Hb), total red
      blood cells (RBC) count, RBC indices, reticulocyte count, packed cell volume
      (PCV), total lymphocyte counts(TLC), differential leukocyte counts (DLC),
      platelet count, and erythrocyte sedimentation rate (ESR). Cut-off values were
      determined as Hb < 10 g/dl, platelet count < 1.5 lakh/cumm, and TLC < 4,000/cumm.
      The group or categorical data were tested for statistical significance using Chi
      square test and Z-test. The difference was reported as significant if P < 0.05.
      RESULTS: (1) Anemia (predominantly normocytic normochromic) was prevalent in
      40.1%, with slightly higher prevalence in those not receiving ART. It occurred
      with high frequency in patients with immunological (42.05%) and clinical acquired
      immunodeficiency disease syndrome (AIDS) (70.58%) compared with those who had an
      asymptomatic HIV infection with CD4 > 200/MUl (28.57%). Patients on zidovudine
      (AZT) therapy had 34.6% anemia with increased mean corpuscular volume (MCV). (2)
      Thrombocytopenia was seen in 3.74% patients (higher percentage in untreated
      patients). (3) Leucopenia was observed in 5.88% in ART-Y (Group A) and 8.14% in
      ART-N (Group B) patients. (4) Pancytopenia was found in 1.6% patients.

PMID- 24014967
TI  - Comparison of Serum Lipid Profiles between Normal Controls and Breast Cancer
      Patients.
AB  - BACKGROUND: Researchers have reported association of plasma/serum lipids and
      lipoproteins with different cancers. Increase levels of circulating lipids and
      lipoproteins have been associated with breast cancer risk. AIM: THE AIM OF THIS
      STUDY IS TO COMPARE SERUM LIPID PROFILES: total-cholesterol (T-CHOL),
      triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density
      lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol
      (VLDL-C) between breast cancer patients and normal participants. MATERIALS AND
      METHODS: A total of 403 women in this study were divided into two groups in the
      period during May 2006-April 2007. Blood samples were collected from 249 patients
      with early stage breast cancer and 154 normal controls for serum lipid profiles
      (T-CHOL, TG, HDL-C, LDL-C and VLDL-C) analysis using Hitachi 717 Autoanalyzer
      (Roche Diagnostic GmbH, Germany). TG, LDL-C and VLDL-C levels in breast cancer
      group were significantly increased as compared with normal controls group (P <
      0.001), whereas HDL-C and T-CHOL levels were not. RESULTS: The results of this
      study suggest that increased serum lipid profiles may associate with breast
      cancer risk in Thai women. Further studies to group important factors including,
      cancer stages, types of cancer, parity, and menopausal status that may affect to
      lipid profiles in breast cancer patients along with an investigation of new lipid
      profiles to clarify most lipid factors that may involve in breast cancer
      development are needed.

PMID- 24014968
TI  - Comparison of various culture methods for isolation of group B streptococcus from
      intrapartum vaginal colonization.
AB  - AIMS: Group B Streptococcus (GBS) is one of the most common causes of neonatal
      sepsis throughout the world. Reports of vaginal colonization of GBS in India are
      few and variable. A study was conducted on pregnant women in a tertiary care
      hospital to compare various methods for isolation of GBS, to study the prevalence
      of GBS in pregnant women in third trimester, and to determine risk factors for
      GBS colonization. SETTINGS AND DESIGN: Observational descriptive study. MATERIALS
      AND METHODS: High vaginal swabs from 150 pregnant women in their third trimester
      were used to compare three methods for isolation of GBS viz. direct culture on 5%
      Sheep Blood agar, direct culture on selective Columbia Blood Agar and culture in
      LIM enrichment broth with subsequent culture on 5% Sheep Blood agar. A history of
      associated risk factors was also taken. STATISTICAL ANALYSIS USED: Statistical
      analysis was performed by Chi-square test. RESULTS: Isolation was best from LIM
      enrichment broth with subsequent culture on 5% Sheep Blood Agar. Prevalence of
      GBS colonization by using culture method was 12.67%. Most frequently associated
      risk factor was intrapartum fever (42.11%). CONCLUSIONS: Standard Culture Method
      using LIM enrichment should be adopted as standard practice for isolation of GBS
      from vaginal swabs.

PMID- 24014969
TI  - Staphylococcal blood stream infections: epidemiology, resistance pattern and
      outcome at a level 1 Indian trauma care center.
AB  - PURPOSE: Blood stream infection (BSI)/bacteremia is a potentially life
      threatening infection and are associated with a high crude mortality. Coagulase
      negative Staphylococcus (CONS) and Staphylococcus aureus are the most commonly
      isolated gram positive bacteria from blood culture samples. While S. aureus is a
      known pathogen causing BSIs, CONS are considered to be common contaminants of
      blood culture. Of late many studies have challenged this traditional viewpoint.
      The aim of this study was to determine the epidemiology and significance of
      Staphylococcus aureus and CONS bacteremia, their resistance patterns and
      associated mortality in critically ill trauma patients admitted to a level 1
      trauma center. MATERIALS AND METHODS: The study was conducted from January 2009
      to June 2011. All patients from whose blood samples yielded a S. aureus or CONS
      on culture were included in this study. A detailed history was obtained and
      follow-up of the patients was done. The isolates of Staphylococci were identified
      to species level. Antibiotic susceptibility was performed by the disc diffusion
      method and VITEK-2 system. RESULTS: During this 30 month period, total of 10,509
      blood samples were received from 2,938 patients. A total of 1,961 samples taken
      from 905 patients were positive for one or more pathogens. S. aureus/CONS were
      isolated from 469 samples from 374 patients. Crude mortality amongst the patients
      having Staphylococcal BSI was 25% (94/374). CONCLUSION: Staphylococcal blood
      stream infections are a leading cause of morbidity and mortality.

PMID- 24014970
TI  - Association of secondary hyperparathyroidism with hemoglobin level in patients
      with chronic kidney disease.
AB  - PURPOSE: Secondary hyperparathyroidism (SHPT) is one of the less recognized
      reasons of anemia in chronic kidney disease (CKD). In this study, we evaluated
      the role of SHPT as a cause of anemia and correlation of intact parathyroid
      hormone (iPTH) and hemoglobin (Hb) level in hemodialysis (HD) patients. METHODS:
      This cross-sectional study was carried out in 63 individuals admitted in HD unit
      of the institute. Serum samples were collected and urea, creatinine, Hb, ferritin
      and iPTH levels were measured. Statistical analysis was carried out using the
      SPSS software (IBM, NY, USA). RESULTS: Mean +/- standard deviation for serum
      urea, creatinine, Hb, ferritin and intact PTH were 177 +/- 15.52, 15.16 +/- 2.28
      mg/dl, 7.03 +/- 2.26 g/dl, 654.7 +/- 563.4 ng/ml, 539.18 +/- 493.59 pg/ml
      respectively. A reverse correlation was found between intact PTH and Hb level.
      CONCLUSIONS: A variety of postulated pathophysiological mechanisms linking SHPT
      and anemia in CKD are discussed. An efficient control of parathyroid hormone
      hypersecretion may be required to achieve a better management of anemia in HD
      patients.

PMID- 24014971
TI  - Primary pulmonary poorly differentiated synovial sarcoma: transducer-like
      enhancer of split 1 immunohistochemistry as a valuable diagnostic aid.
AB  - Poorly differentiated primary pulmonary synovial sarcomas are rare and
      challenging for a surgical pathologist to diagnose. Although the demonstration of
      the tumor specific translocation, t (x; 18)(p11.2;q11.2) or the resultant fusion
      gene (SYT-SSX) is the gold standard for diagnosis, this test is not always
      accessible. We report the use of immunohistochemistry, including transducer-like
      enhancer of split-1 in the diagnosis of one such tumor in a young individual. 

PMID- 24014972
TI  - Iatrogenic Infection of Clostridium welchii Following Intramuscular Injection of
      Sodium Diclofenac.
AB  - Injection site abscess is an iatrogenic infection. Intramuscular (IM) injection
      is a common route to administer medication. Microorganisms known to cause
      injection site abscess are Staphylococcus aureus, Pseudomonas, Klebsiella,
      Escherichia coli commonly, Atypical mycobacteria, Clostridium species rarely. Gas
      gangrene is a necrotic infection of soft tissue with high mortality, often
      necessitating amputation in order to control the infection. Here, presenting a
      case of gas gangrene in a 19-year-old healthy male, who developed a life
      threatening infection after IM injection of sodium diclofenac. Prompt clinical
      diagnosis, laboratory support, and timely surgical intervention saved the
      patient's life. 

PMID- 24014973
TI  - Axillary schwannoma with extensive cystic degeneration.
AB  - Schwannoma affect mainly head, neck, and flexor aspect of the limbs. Neurogenic
      tumors arising from the brachial plexus are rare and axillary schwannoma is
      extremely uncommon. Cystic degeneration is common in longstanding cases and which
      when aspirated may yield only macrophages or lymphocytes leading to false
      diagnosis of the case in spite of strong clinical suspicion. We report one such
      rare case of a solitary axillary schwannoma with extensive cystic degeneration,
      which was misdiagnosed on fine needle aspiration cytology and subsequently
      confirmed by the histopathological examination and immunohistochemistry. 

PMID- 24014974
TI  - Melanoacanthoma of external ear: report of two cases.
AB  - Melanoacanthoma is a rare lesion. Melanoacanthoma of external ear is still rarer.
      We present two cases of melanoacanthoma of external ear in adults which presented
      as pigmented growths and clinically were suspected as malignant lesions.
      Histopathology was diagnostic as it demonstrated the characteristic elevated
      lesion with abundant melanin pigment. No recurrence of the lesion was reported
      after four years of initial diagnosis. These cases have been presented because of
      their uncommon location, highlighting the differential diagnoses. 

PMID- 24014975
TI  - Limb body wall complex: a rare anomaly.
AB  - We present autopsy findings of a case of limb body wall complex (LBWC). The fetus
      had encephalocele, genitourinary agenesis, skeletal anomalies and body wall
      defects. The rare finding in our case is the occurrence of both cranial and
      urogenital anomalies. The presence of complex anomalies in this fetus, supports
      embryonal dysplasia theory of pathogenesis for LBWC. 

PMID- 24014976
TI  - Congenital pseudoarthrosis tibia with fibrous hamartoma in a child with
      neurofibromatosis.

PMID- 24014977
TI  - Beyond a typical thyroid eye disease.

PMID- 24014978
TI  - Eyelid masses: a 10-year survey from a tertiary eye hospital in Tehran.
AB  - PURPOSE: The purpose of this study was to evaluate the demographics and clinical
      features of eyelid masses in a tertiary eye hospital over a 10-year period.
      MATERIALS AND METHODS: A retrospective chart review was performed for patients
      admitted with eyelid tumors from 2000 to 2010. Data were collected and analyzed
      on the demographic features, location of the tumor, types of treatment, and
      pathologic findings. RESULTS: A total number of 182 patients were evaluated of
      which, 82 cases were benign and 100 cases were malignant neoplasms. The most
      common benign tumors included melanocytic nevi (35%), papilloma (19.5%), and
      cysts (11%). The most frequent malignant tumors included basal cell carcinoma
      (BCC) (83%), squamous cell carcinoma (8%) and sebaceous gland carcinoma (6%). The
      most common site for malignancy was the lower lid followed by the upper lid. BCC
      recurred in 16 cases that were most frequent in the lower lid. CONCLUSION:
      Melanocytic nevus, papilloma and cysts are the most common benign lesions and BCC
      is the most common malignant lesion in the eyelids. Recurrence is a feature of
      BCC especially in the lower lid.

PMID- 24014980
TI  - Etiology of tearing in patients seen in an oculoplastic clinic in Saudi Arabia.
AB  - AIM: To determine the prevalence of various causes of tearing among patients
      referred to an oculoplastic clinic. MATERIALS AND METHODS: A prospective study on
      all patients seen in an oculoplastic clinic with a chief complaint of tearing.
      The cause of tearing was determined on the basis of the anatomical location of
      the primary etiology. RESULTS: This study included 357 patients with a mean age
      53.9 years. Punctal stenosis was the most common etiology, affecting 37.8% of the
      patients. Among patients with punctual stenosis, 63.4% were women over 50-year
      old (P = 0.001); 55.6% had tearing for less than 6 months (P = 0.038), and all of
      them had associated chronic blepharitis. The remaining study participants had dry
      eye with reflex tearing (27.7%), nasolacrimal duct obstruction (10.1%),
      canalicular obstruction (4.2%), entropion or ectropion (3.4%), pterygium (1.7%),
      megalo-caruncle (1.7%), and functional tearing (1.7%). CONCLUSION: The outcomes
      of this study indicate the most common cause of tearing is punctal pathology.
      Therefore, slit lamp evaluation with careful attention to the punctum is
      warranted in all patients with tearing.

PMID- 24014979
TI  - Anterior orbit and adnexal amyloidosis.
AB  - PURPOSE: To describe six cases of anterior orbital and adnexal amyloidosis and to
      report on proteomic analysis to characterize the nature of amyloid in archived
      biopsies in two cases. MATERIALS AND METHODS: The clinical features, radiological
      findings, pathology, and outcome of six patients with anterior orbit and adnexal
      amyloidosis were retrieved from the medical records. The biochemical nature of
      the amyloid was determined using liquid chromatography/mass spectroscopy archived
      paraffin-embedded tissue in two cases. RESULTS: Of the six cases, three had
      unilateral localized anterior orbit and lacrimal gland involvement. Four of the
      six patients were female with an average duration of 12.8 years from the time of
      onset to presentation eyelid infiltration by amyloid caused ptosis in five cases.
      CT scan in patients with lacrimal gland involvement (n = 3) demonstrated
      calcified deformable anterior orbital masses and on pathological
      exmaintionamyloid and calcific deposits replaced the lacrimal gland acini. Ptosis
      repair was performed in three patients with good outcomes. One patient required
      repeated debulking of the mass and one patient had recurrenct disease. Proteomic
      analysis revealed polyclonal IgG-associated amyloid deposition in one patient and
      AL kappa amyloid in the second patient. CONCLUSION: Amyloidosis of the anterior
      orbit and lacrimal gland can present with a wide spectrum of findings with good
      outcomes after surgical excision. The nature of amyloid material can be precisely
      determined in archival pathology blocks using diagnostic proteomic analysis.

PMID- 24014981
TI  - Comparison of corneal curvature and anterior chamber depth measurements using the
      manual keratometer, Lenstar LS 900 and the Pentacam.
AB  - PURPOSE: The purpose of this study was to compare keratometry and anterior
      chamber depth (ACD) measurements from the Lenstar LS 900 (Haag-Streit AG,
      Switzerland) and the Pentacam (Oculus, Weltzar, Germany), and compare the
      keratometry readings of these two systems to a manual keratometer (MK), (Haag
      Streit, Switzerland). MATERIALS AND METHODS: In this prospective study,
      keratometry and ACD measurements were obtained in 50 eyes of 50 normal subjects
      with the Lenstar and the Pentacam. Keratometry was also measured using a MK.
      Correlation, comparison, and interdevice agreement was evaluated using intraclass
      correlation analysis, Wilcoxon test, and Bland-Altman plots. RESULTS: The
      keratometry and ACD measurements obtained from the Lenstar and the Pentacam
      showed excellent correlation. The mean interdevice differences in mean
      keratometry (Km) for the Lenstar and the Pentacam, the Lenstar and the MK, and
      the Pentacam and the MK were 0.39 D, 0.10 D, and 0.30 D respectively; and the 95%
      limits of agreement (LoA) for Km were 0.04-0.82 D; -1.90-2.10 D; and -2.30-1.70
      D, respectively. The mean interdevice difference in ACD for the Lenstar versus
      the Pentacam was 0.09 mm, with 95% LoA of 0.23-0.05 mm. CONCLUSIONS: The ACD
      measurements obtained using the Lenstar and the Pentacam seem to be
      interchangeable, whereas, the keratometry measurements obtained using the
      Lenstar, Pentacam, and MK differ considerably, and are not interchangeable.

PMID- 24014982
TI  - Diffractive multifocal intraocular lens compared to pseudo-accommodative
      intraocular lens implant for unilateral cataracts in pre-presbyopic patients.
AB  - PURPOSE: To evaluate the efficacy of diffractive multifocal and pseudo
      accommodative IOLs in pre-presbyopes with cataract. MATERIALS AND METHODS: A
      prospective randomized control study was performed on patients with cataract in
      the pre-presbyopic age group. Patients were randomly allocated to 2 groups: Group
      1 comprised 12 patients who underwent implantation of a diffractive multifocal
      IOL and Group 2 comprised 13 patients who underwent implantation of a pseudo
      accommodative IOL after standard phacoemulsification. Efficacy was measured by
      postoperative distance and near uncorrected visual acuity, contrast sensitivity,
      spectacle independence, and glare and halo. RESULTS: The study patients were aged
      22-35 years and included 14 females and 11 males. All examinations were performed
      6 months postoperatively by a second observer unaware of the study objectives.
      Mean uncorrected distance visual acuity was 0.125 +/- 0.1 LogMAR in Group 1 and
      0.1385 +/- 0.1 in Group 2 (P = 0.7993). Near visual acuity was 0.0917 +/- 0.1 in
      Group 1 and 0.386 +/- 0.2 in Group 2 (P < 0.0001). Contrast sensitivity was good
      in both groups based on the Pelli-Robson chart (P = 0.3919). Night-time glare was
      present in 3 (25%) patients in Group 1 and in 2 (15.4%) patients in Group 2. No
      patients in either group had difficulty driving during the day or night. Ten
      patients in Group 1 (83.3%) and 7 patients in Group 2 (53.85%) had spectacle
      independence (P = 0.1249). CONCLUSION: Greater proportions of patients who
      underwent diffractive multifocal implantation achieved functional distance and
      near vision as compared to those in the pseudo-accommodative IOL group. There was
      greater variability in near vision in patients who received the pseudo
      accommodative IOL as compared to those in the multifocal IOLs. Contrast
      sensitivity remained adequate in both the groups. There were more glare and halos
      in the multifocal group as compared to those in the pseudo-accommodative group.
      More patients achieved spectacle independence with multifocal IOLs.

PMID- 24014983
TI  - Anterior segment study with the Pentacam Scheimpflug camera in refractive surgery
      candidates.
AB  - PURPOSE: The purpose of this study was to evaluate the anterior segment
      measurements according to refractive status in a sample of the Iranian
      population. SETTING: Rassoul Akram Hospital, Tehran University of Medical
      Sciences. MATERIAL AND METHODS: IN THIS STUDY, REFRACTIVE SURGERY CANDIDATES WERE
      ASSIGNED ACCORDING TO THE REFRACTIVE ERROR TO ONE OF THREE GROUPS : emmetropia,
      myopia, and hyperopia. Myopic eyes were further divided to four subgroups :
      simple myopic group, simple myopic astigmatism group, high myopic group, and high
      myopia with astigmatism group. Anterior segment measurements with the Pentacam
      Scheimpflug system were performed in the right eye of all subjects. RESULTS: The
      study sample was comprised of 283 subjects with a mean age of 29.1 +/- 7.5
      (standard deviation) years. Mean keratometry reading, Anterior chamber depth
      (ACD) and volume measurements were significantly higher in the myopic group and
      mean keratometry reading and anterior chamber angle measurements were
      significantly lower in the hyperopic group (P < 0.05, all comparisons). Maximum
      anterior elevation (AEmax) and maximum posterior elevation (PEmax), Q value,
      progression index, minimum corneal thickness, and corneal volume measurements
      were similar for all groups (P > 0.05, all comparisons). In the myopic subgroups,
      AEmax and PEmax and maximum keratometry (Kmax) were significantly higher, and ACD
      was lower in the astigmatic groups (P < 0.05, all comparisons). The Q value was
      less negative in low myopia (P < 0.05). CONCLUSIONS: Myopic eyes had steeper
      corneas than hyperopic eyes and anterior chamber measurements were significantly
      higher in the myopic eyes. In myopic eyes, AEmax and PEmax and Kmax measurements
      were higher, and ACD measurements were lower in the astigmatic groups.

PMID- 24014984
TI  - Results of cataract surgery and plasma ablation posterior capsulotomy in anterior
      persistent hyperplastic primary vitreous.
AB  - PURPOSE: To report the feasibility and outcome of lens aspiration, and Fugo blade
      assisted capsulotomy and anterior vitrectomy in eyes with anterior persistent
      hyperplastic primary vitreous (PHPV). MATERIALS AND METHODS: In this case series,
      10 eyes of 10 patients with anterior PHPV underwent lens aspiration. The
      vascularized posterior capsule was cut with a Fugo blade (plasma knife) and
      removed with a vitrector. A foldable posterior chamber intraocular lens (IOL) was
      implanted in eight eyes and the outcomes were evaluated. RESULTS: The mean age of
      patients was 16.8 +/- 6.37 months (range: 5 to 28 months). The surgery was
      completed successfully in all eyes. There were no cases of intraocular hemorrhage
      intraoperatively. Foldable acrylic IOL was implanted in the bag in 3 eyes and in
      the sulcus in 5 eyes. Two eyes were microphthalmic and did no undergo IOL
      implantation (aphakic). None of the eyes had a significant reaction or elevated
      intraocular pressure postoperatively. The follow-up ranged from 4 to 21 months.
      All the pseudophakic eyes achieved a best corrected visual acuity of >=20/200
      with 50% (4/8) of these eyes with >=20/60 vision. CONCLUSION: Lens aspiration
      followed by posterior capsulotomy with Fugo blade-assisted plasma ablation is a
      feasible technique for performing successful lens surgery in cases with florid
      anterior PHPV.

PMID- 24014985
TI  - A single drop of 0.5% proparacaine hydrochloride for uncomplicated clear corneal
      phacoemulsification.
AB  - PURPOSE: The purpose of this study was to compare the efficacy of a single drop
      of 0.5% proparacaine hydrochloride in uncomplicated cataract surgery with
      phacoemulsification. MATERIALS AND METHODS: Two hundred and ninety five patients
      scheduled for the phacoemulsification were divided into 2 groups based on the
      anesthetic agents they were to receive: 146 patients who received a single drop
      of 0.5% proparacaine 2 min before the start of the surgery (proparacaine group)
      and; 149 patients who received supplementation of 0.5% intracameral preservative
      free xylocaine (xylocaine group). A single surgeon performed all surgeries.
      Intraoperative and post-operative pain scores were evaluated on a visual analog
      scale. The surgeon noted his subjective impression of corneal clarity, discomfort
      while performing the surgery any supplemental anesthesia required and
      intraoperative complications. An anesthetist noted vital parameters and the need
      for intravenous sedation. Total surgical time was noted. Comparison of parameters
      was performed with the Chi-square test, and A P value less than 0.05 was
      considered as statistically significant. RESULTS: No statistically significant
      difference was seen in the intraoperative (P = 0.24) and post-operative (P =
      0.164) pain scores between groups. There was no pain (0 score) in 41.8% of
      patients in the proparacaine group and 46.3% of patients in the xylocaine group.
      The average surgical time (P = 0.279) and surgeon discomfort (P = 0.07) were not
      statistically significantly different between groups. No patients required
      supplemental anesthesia. There were no surgical complications that could
      compromise the visual outcome. An equal number of patients in both groups
      preferred same type of anesthetic technique for the fellow eye cataract surgery
      (89.11% for the proparacaine group and 90.18% for the xylocaine group). No
      patients in either group had changes in vital parameters or required intravenous
      sedation. CONCLUSION: A single drop pre-operatively, of proparacaine
      hydrochloride was comparable to the intracameral supplementation of preservative
      free xylocaine for phacoemulsification in uncomplicated cataract surgery without
      compromising the visual outcome. However, we recommend individualizing the
      anesthetic technique according to the requirements of the surgeon.

PMID- 24014986
TI  - Loop suture technique for optional adjustment in strabismus surgery.
AB  - PURPOSE: To describe a loop suture technique that allows intraoperative
      conjunctival closure and later optional suture adjustment in strabismus surgery
      in uncooperative patients. MATERIALS AND METHODS: This retrospective case series
      comprised 25 patients. After a recessed or resected horizontal muscle was secured
      to the sclera with a primary suture suspended back 2 mm, a second loop suture was
      passed through the body of the muscle and under the primary suture knot. The loop
      suture could be removed later while the patient was awake, or it could be tied to
      advance the muscle. Success was defined as a residual deviation of 10 prism
      diopters (PD) or less at 2 months postoperatively. RESULTS: In the study cohort,
      20 patients had successful alignment at 2 months (80%). Six patients (24%)
      underwent postoperative suture tightening by the loop technique, and each muscle
      affected the alignment an average of 7.7 PD (+/-3.8 PD). No patients underwent a
      reoperation within the first 2 months. One patient had a pyogenic granuloma (4%).
      CONCLUSIONS: The loop suture technique permits optional postoperative tightening
      of muscles and avoids sedation in children or uncooperative patients not
      requiring adjustment.

PMID- 24014987
TI  - Barriers to cataract surgical uptake in central ethiopia.
AB  - PURPOSE: The aim of this study was to assess the factors that delay surgical
      intervention in patients suffering from age related mature cataract in Ethiopia.
      MATERIALS AND METHODS: A short term descriptive study was performed that
      evaluated patients with mature cataract presenting to outreach eye care clinics
      in rural central Ethiopia. Patients were interviewed to determine the reasons for
      delay in their cataract surgeries. RESULT: A total of 146 subjects (57 male and
      89 females) with operable age related cataract were evaluated at 31 outreach
      clinics. Over 86% of the respondents were above 55 years of age, (range, 45-78
      years). The male to female ratio was 1:1.5 and 30.2% of the subjects were blind
      bilaterally (best corrected visual acuity <3/60). The majority of the respondents
      were farmers (53.4%) and 86.3% were illiterate. The major factors that delayed
      cataract surgery included: Cost of surgery (91.8%), insufficient family income
      (78.1%), good vision in the fellow (unaffected) eye (39.7%), and the distance to
      hospital from their village (47.9%). CONCLUSION: Surgical cost, insufficient
      family income, and the distance to an eye care centre were the major factors
      delaying cataract surgery in rural Ethiopia.

PMID- 24014988
TI  - Efficacy of intacs intrastromal corneal ring segment relative to depth of
      insertion evaluated with anterior segment optical coherence tomography.
AB  - AIM: To evaluate the effect of implantation depth of Intacs microthin
      prescription inserts (Addition Technology Inc, Fremont, California) on visual and
      topographic outcomes in patients with post- laser-assisted in situ keratomileusis
      (LASIK) ectasias. SETTINGS AND DESIGN: Retrospective, observational case series.
      MATERIALS AND METHODS: In this case series, 16 eyes of 12 patients were
      evaluated. All cases were post-LASIK ectasia that had undergone intrastromal
      corneal ring segment (ICRS) implantation. The planned insertion depth was 70% of
      stromal thickness using a manual dissector. At least 12 months postoperatively,
      all eyes underwent Visante (Carl Zeiss Meditec) AS-OCT to determine insertion
      depth. Cases were categorized into 3 groups based on the measured implantation
      depth: 40-59% thickness; 60-79% thickness; and >=80% thickness. Visual,
      refractive and topographic outcomes were evaluated relative to implantation
      depth. RESULTS: The lowest improvement in the study parameters ocurred when the
      implantation depth was >=80%. In this group, uncorrected visual acuity (UCVA) and
      best spectacle corrected VA (BSCVA) improved less than 0.5 lines. Manifest
      refractive spherical equivalent (MRSE) and mean keratometry (Km) change was less
      than 0.5 diopters (D). The greatest improvements were observed with implantation
      depth of 60-79% where UCVA and BSCVA increased by 4.5 and 2.5 lines respectively,
      and MRSE and Km changed by approximately 2.00 D. Less improvement was found when
      ICRS were implanted between 40-59% of stromal thickness. CONCLUSION: Implantation
      of ICRS greater than 80% of stromal thickness may have no effect on visual and
      topographic status.

PMID- 24014989
TI  - Autologous cryoprecipitate for attaching conjunctival autografts after pterygium
      excision.
AB  - PURPOSE: To report the efficacy, safety, and reliability of autologous
      cryoprecipitate in pterygium excision surgery and to compare it with the
      traditional method of using absorbable sutures, in regard to surgical time and
      the patient comfort. MATERIALS AND METHODS: A prospective interventional clinical
      study was carried out in a specialized eye clinic. A total of 54 patients (90
      eyes) underwent surgical excision of the nasal pterygium (whether primary or
      recurrent) with conjunctival autograft obtained from the same eye. Patients were
      divided into two groups. Autologous cryoprecipitate was used in 47 eyes (glue
      group), and absorbable sutures (8/0 vicryl) were used in 43 eyes (suture group)
      to attach the free conjunctival graft. There were 42 primary and 48 recurrent
      nasal pterygia that were included in the study. The surgical time was noted, and
      post-operative pain was graded. Follow-up period ranged from 6 months to 18
      months (mean 12 months). P < 0.05 was statistically significant. RESULTS: The
      medians of the visual analogue scale values were significantly lower in the glue
      group (P < 0.05). The median surgical time was statistically significantly lower
      at 11 min (range 9 min to 15 min) in the glue group, compared to 21 min (range 12
      min to 28 min) for the suture group (P < 0.05). No significant intraoperative or
      post-operative complications were noted. Recurrence rate was 12%, and all
      recurrence cases occurred in the sutures group. CONCLUSIONS: Application of
      autologous cryoprecipitate glue instead of sutures for attaching the free
      conjunctival graft in pterygium surgery resulted in less post-operative pain and
      shorter surgical time. Additionally, there were no cases of recurrence during the
      follow-up in patients who received autologous cryoprecipitate glue during
      pterygium surgery.

PMID- 24014990
TI  - Vitrectomy for posterior segment intraocular foreign bodies, visual and
      anatomical outcomes.
AB  - PURPOSE: To evaluate the visual and anatomic results and determine the prognostic
      factors after pars plana vitrectomy and posterior segment intraocular foreign
      body (IOFB) removal. MATERIALS AND METHODS: This retrospective study reviews the
      patients' charts of 48 consecutive patients with posterior segment IOFB who
      underwent pars plana vitrectomy and IOFB removal over a 4-year period, recently.
      Association between visual outcome and various preoperative, operative, and
      postoperative variables was statistically analyzed. Data were analyzed with the
      paired t-test and the chi square test. Statistical significance was indicated by
      P < 0.05. RESULTS: The mean interval between the time of injury and IOFB removal
      was 24 +/- 43.1 days and 27 (53%) eyes underwent IOFB removal within 7 days of
      the injury. Nine (19.1%) patients achieved a visual acuity of 20/40 or better. An
      improvement of visual acuity of at least three lines occurred in 21 (44.6%) eyes
      and the vision remained unchanged in 15 (31.9%) eyes. Postoperative retinal
      detachment occurred in five (10.6%) eyes. Visual improvement was more likely to
      occur in eyes with lower levels of presenting visual acuity (P = 0.2). Visual
      improvement was not associated with an entry site and IOFB location, lens injury,
      time to surgery, and pre- and post-operative retinal detachment. At the end of
      follow up, anatomical success was achieved in 97.9% of eyes. CONCLUSIONS: High
      anatomical success could be achieved after the removal of posterior segment IOFBs
      by vitrectomy, despite a delay in surgery. Poor visual outcome may be mainly due
      to the initial ocular injury.

PMID- 24014991
TI  - Albinism: particular attention to the ocular motor system.
AB  - The purpose of this report is to summarize an understanding of the ocular motor
      system in patients with albinism. Other than the association of vertical
      eccentric gaze null positions and asymmetric, (a) periodic alternating nystagmus
      in a large percentage of patients, the ocular motor system in human albinism does
      not contain unique pathology, rather has "typical" types of infantile ocular
      oscillations and binocular disorders. Both the ocular motor and afferent visual
      system are affected to varying degrees in patients with albinism, thus, combined
      treatment of both systems will maximize visual function.

PMID- 24014992
TI  - Successful use of intravitreal bevacizumab and pascal laser photocoagulation in
      the management of adult Coats' disease.
AB  - Traditional methods of managing exudative retinal detachment secondary to Coats'
      disease have been associated with varying degrees of success. We describe a case
      of a 34 year-old male who presented with a sub-total exudative retinal detachment
      of the right eye that encroached upon the macula, associated with a
      vasoproliferative tumor secondary to Coats' disease. The patient under-went
      successful treatment with two intravitreal injections of bevacizumab (Avastin,
      Genetech Inc., San Francisco, CA, USA) combined with targeted laser
      photocoagulation with a 532 nm Pascal laser (Topcon Corp., Tokyo, Japan). The
      visual acuity improved 5 days after the second intravitreal injection from 6/18
      to 6/5, with no residual macular edema and complete regression of the
      vasoproliferative tumor. The improvement in visual acuity was maintained at 12
      months post-treatment. We believe this is the first case report describing the
      successful use of Pascal laser photocoagulation with intravitreal bevacizumab in
      the treatment of Coats' disease. Our aim was to defer laser treatment until 'near
      total' retinal reattachment and regression of the vasoproliferative tumor was
      achieved. There are, however, reports of vitreous fibrosis in patients with
      Coats' disease treated with intravitreal bevacizumab. This suggests further long
      term follow-up studies are required in patients treated with this approach.

PMID- 24014993
TI  - Eyelid angiosarcoma: a case report and review of the literature.
AB  - A 77-year-old woman presented with a 3-month history of a lesion on her left
      lower eyelid. External examination showed a tan-colored nodule with an overlying
      crust-covered ulcer on the left lower eyelid, nasally. The ulcer measured 12 mm *
      7 mm. Complete surgical excision with a frozen section margin control was
      performed. Histopathological examination showed islands and sheets of spindle and
      epithelioid cells with little intervening stroma. The cells had copious amounts
      of either rounded or tapered eosinophilic cytoplasm with occasional
      intracytoplasmic lumina and large vesicular nuclei with prominent nucleoli. There
      was intense immunoreactivity for CD34, CD31, factor VIII, and Ki-67. The
      diagnosis was eyelid angiosarcoma. The patient refused any further therapy. At 1
      year follow-up, there was no recurrence or development of metastasis. In
      conclusion, tan-colored eyelid nodules with overlying ulcer are usually a basal
      cell carcinoma; however, rarely it can be an eyelid angiosarcoma.

PMID- 24014994
TI  - Bilateral congenital lacrimal fistula in Down syndrome.
AB  - Congenital lacrimal fistulae are rare in Down syndrome and bilateral presentation
      is very unusual. It can be associated with nasolacrimal duct obstruction. We
      report a 3-year-old female with Down syndrome who presented with watering and
      discharge from both eyes and bilateral fistulous openings present inferonasal to
      the medial canthus. Upon examination, the lacrimal sac regurgitation test was
      positive on both sides. Our case report documents a distinctive case of bilateral
      congenital lacrimal fistulae in association with Down syndrome. It was managed
      successfully by primary fistulectomy and nasolacrimal duct probing.

PMID- 24014995
TI  - Acute hydrops in the donor cornea graft in non-keratoconus patients.
AB  - A 44-year-old Hispanic male and 91-year-old Caucasian male presented to the
      clinic with acute vision loss and pain years after penetrating keratoplasty
      (PKP). Neither patient had a history of keratoconus. Both patients had a history
      of eye rubbing and intraocular device present in the anterior chamber. The first
      patient had a history of a glaucoma drainage tube and the second patient had an
      anterior chamber intraocular lens implanted. Anterior segment ocular coherence
      tomography showed deep stromal cystic cavities. Both patients exhibited breaks in
      the endothelium by ultrasound biomicroscopy and the histopathologic examination
      after repeat PKP. Those findings were most consistent with acute corneal hydrops
      in the donor graft.

PMID- 24014996
TI  - Oculocardiac reflex in a medial orbital wall fracture without clinically evident
      entrapment.
AB  - In this report, we describe a patient with a medial wall orbital fracture, who
      presented with vasovagal-like symptoms secondary to an oculocardiac reflex. This
      case is unusual because the patient had no other clinical evidence of muscle
      entrapment. A 15-year-old male presented with daily 5-10 min episodes of
      dizziness, light headedness, and nausea consistent with a vasovagal reaction. On
      examination, the patient had full extra ocular motility and was orthotropic in
      all fields of gaze. On computed tomography a comminuted medial orbital wall
      fracture was identified. The adjacent medial rectus muscle was in normal
      position, but was "rounded" relative to the contralateral side. The patient
      underwent fracture repair with immediate resolution of all symptoms. Symptoms
      related to a vasovagal response may occur with orbital fractures despite normal
      extra ocular motility. Presumably this relates to tension or pulling on an extra
      ocular muscle, which is not to a degree that alteration in function is
      appreciable clinically.

PMID- 24014997
TI  - Does raisins protect against cavities?

PMID- 24014998
TI  - The effect of four sprue shapes on the quality of cobalt-chromium cast removable
      partial denture frame-works.
AB  - STATEMENT OF PROBLEM: Sprue design is a factor that controls the velocity and
      adequate supply of metal to the mould. Currently various manufacturers recommend
      different shapes of sprue, which have not been advocated in textbooks and
      literature is lacking for their routine applications. PURPOSE: This in vitro
      study was carried out to determine the efficacy of four sprue shapes in producing
      complete, void free cobalt-chrome removable partial denture frameworks. MATERIALS
      AND METHODS: A brass metal die with a Kennedy class III, modification 1,
      partially edentulous arch was used and four sprue shapes (Group A-Ribbon, Group B
      Square, Group C-Round and Group D- Round with reservoir) were evaluated. 40
      refractory casts were made, 10 wax patterns for each sprue design were waxed up,
      invested with phosphate bonded investment material and castings done with
      induction casting machine by the same operator under standardized protocols. The
      cast frameworks were evaluated for 1. The defects observed visually before
      finishing and polishing procedures, 2. Fit on the master die as seen with naked
      eye and 3. Defects on radiographic evaluation. Data were tabulated and
      statistically analyzed with 1-way ANOVA followed by Student 't' test. RESULTS:
      The results differed significantly (P < 0.0001) between the Groups with maximum
      defects in the castings of Group A followed in decreasing order by Group B, Group
      C and Group D. When comparing between the Groups (P < 0.05), the defects in
      Groups C and D was significantly lower than Group A and Group B. CONCLUSIONS:
      Round sprues with reservoir produced most satisfactory fit of castings with
      minimum number of internal and external defects.

PMID- 24014999
TI  - A comparative evaluation of the retention of metallic brackets bonded with resin
      modified glass ionomer cement under different enamel preparations: A pilot study.
AB  - INTRODUCTION: For orthodontists, the ideal bonding material should be less
      moisture-sensitive and should release fluoride, thereby reducing unfavorable
      iatrogenic decalcification. Resin-Modified Glass Ionomer Cements (RMGICs), due to
      their ability to bond in the presence of saliva and blood can be a very good
      bonding agent for orthodontic attachments especially in the areas of mouth, which
      are difficult to access. Moreover, their fluoride releasing property makes them
      an ideal bonding agent for patients with poor oral hygiene. However, their
      immediate bond strength is said to be too low to immediately ligate the initial
      wire, which could increase the total number of appointments. The effect of
      sandblasting and the use of sodium hypochlorite (NaOCL) on the immediate bond
      failure of RMGIC clinically have not been reported in the literature until the
      date. This investigation intended to assess the effect of sandblasting (of the
      bracket base and enamel) and NaOCL on the rate of bond failure (with immediate
      ligation at 30 min) of Fuji Ortho LC and its comparison with that of conventional
      light cured composite resin over a period of 1 year. MATERIALS AND METHODS: 400
      sample teeth were further divided into 4 groups of 100 each and bonded as
      follows: (1) Group 1: Normal metallic brackets bonded with Fuji Ortho LC. (2)
      Group 2: Sandblasted bracket base and enamel surface, brackets bonded with Fuji
      Ortho LC. (3) Group 3: Deproteinized enamel surface using sodium hypochlorite and
      brackets bonded with Fuji Ortho LC. (4) Group 4: Normal metallic bracket bonded
      with Transbond XT after etching enamel with 37% phosphoric acid. This group
      served as control group. RESULTS AND CONCLUSION: Results showed that sandblasting
      the bracket base and enamel, can significantly reduce the bond failure rate of
      RMGIC.

PMID- 24015000
TI  - Comparative evaluation of surface porosities in conventional heat polymerized
      acrylic resin cured by water bath and microwave energy with microwavable acrylic
      resin cured by microwave energy.
AB  - BACKGROUND: Conventional heat cure poly methyl methacrylate (PMMA) is the most
      commonly used denture base resin despite having some short comings. Lengthy
      polymerization time being one of them and in order to overcome this fact
      microwave curing method was recommended. Unavailability of specially designed
      microwavable acrylic resin made it unpopular. Therefore, in this study,
      conventional heat cure PMMA was polymerized by microwave energy. AIM AND
      OBJECTIVES: This study was designed to evaluate the surface porosities in PMMA
      cured by conventional water bath and microwave energy and compare it with
      microwavable acrylic resin cured by microwave energy. MATERIALS AND METHODS: Wax
      samples were obtained by pouring molten wax into a metal mold of 25 mm * 12 mm *
      3 mm dimensions. These samples were divided into three groups namely C, CM, and
      M. Group C denotes conventional heat cure PMMA cured by water bath method, CM
      denotes conventional heat cure PMMA cured by microwave energy, M denotes
      specially designed microwavable acrylic denture base resin cured by microwave
      energy. After polymerization, each sample was scanned in three pre-marked areas
      for surface porosities using the optical microscope. As per the literature
      available, this instrument is being used for the first time to measure the
      porosity in acrylic resin. It is a reliable method of measuring area of surface
      pores. Portion of the sample being scanned is displayed on the computer and with
      the help of software area of each pore was measured and data were analyzed.
      RESULTS: Conventional heat cure PMMA samples cured by microwave energy showed
      maximum porosities than the samples cured by conventional water bath method and
      microwavable acrylic resin cured by microwave energy. Higher percentage of
      porosities was statistically significant, but well within the range to be
      clinically acceptable. CONCLUSION: Within the limitations of this in-vitro study,
      conventional heat cure PMMA can be cured by microwave energy without compromising
      on its property such as surface porosity.

PMID- 24015001
TI  - Distance and protective barrier effects on the composite resin degree of
      conversion.
AB  - CONTEXT: The food wrap films are used to cover the tip of curing light units in
      order to avoid contamination and prevent damage to the light guide. However,
      their effects on resin polymerization are not fully known. AIMS: We investigated
      the effects on restoration efficiency of a food wrap protective barrier used on
      the tip of curing light units. MATERIALS AND METHODS: For each treatment, five
      replications were performed, a total of 60 bovine incisor. The degree of
      conversion (%DC) of restorations with the composite resin Opallis EA2 was
      evaluated using 3 curing light devices (Optilux 501, Optilight and Ultra LED) and
      2 curing distances (0 and 5 mm). The composite resin was tested for restoration
      of cavities in bovine crowns. %DC values were measured by the Fourier transform
      infrared spectroscopy-attenuated total reflectance technique. STATISTICAL
      ANALYSIS USED: The data were analyzed using 3-way ANOVA and Tukey's test.
      RESULTS: Use of the protective film lowered %DC (F = 4.13; P = 0.05), and the
      effects of curing distance were associated to the curing light device (F = 3.61;
      P = 0.03). CONCLUSIONS: The distance from the light curing tip and use of a
      translucent protective barrier on the light-cure device can both impair composite
      resin %DC.

PMID- 24015002
TI  - Comparison of the efficacy of chlorhexidine varnish and chip in the treatment of
      chronic periodontitis.
AB  - BACKGROUND: The purpose of this study was to clinically evaluate the benefits of
      sub gingival chlorhexidine (CHX) varnish and biodegradable CHX chip application
      used as an adjunct to scaling and root planning (SRP) as combined therapy and
      also to compare the effect of combined therapy with SRP alone. MATERIALS AND
      METHODS: Fifteen patients with at least three sites with a probing pocket depth
      (PPD) of 5-8 mm were considered. Following baseline evaluation, all three sites
      were subjected for SRP. After completing SRP, each site was randomly subjected
      for CHX varnish, CHX chip application and the 3(rd) site was left without any
      medication as a control. Clinical parameters such as sulcus bleeding index,
      plaque index, bleeding on probing (BOP), PPD, and clinical attachment level (CAL)
      were recorded at baseline, 1 month and 3 months post-operatively. RESULTS: All
      three groups presented with an improvement in clinical parameters compared to
      baseline. The mean reduction in PPD was 2.4 mm in SRP sites, 2.5 mm in SRP + CHX
      varnish sites and 2.8 mm in SRP + CHX chip sites. The mean gain in CAL was 2.4 mm
      in SRP sites, 2.3 mm in SRP + CHX varnish sites and 2.8 mm SRP + CHX chip sites.
      INTERPRETATION AND CONCLUSION: The present study indicated that application of
      CHX varnish and placement of CHX chip as an adjunct to SRP produced a clinically
      significant reduction in the PPD, BOP and a gain in CAL at 30(th) day and 90(th)
      day from baseline when compared to SRP alone. The results though were not
      statistically significant.

PMID- 24015003
TI  - A clinical study of the variation in horizontal condylar guidance obtained by
      using three anterior points of reference and two different articulator systems.
AB  - BACKGROUND AND OBJECTIVES: For mounting the maxillary cast to articulator,
      minimum three reference points not on single line, decide the plane to which
      maxillary cast is mounted. Variations exist in condylar guidance when different
      anterior reference points are used to mount the cast. Type of articulator may
      have influence on condylar guidance. A clinical study was planned to evaluate the
      effects of different anterior points of reference and two different articulator
      systems on condylar guidance. MATERIALS AND METHODS: Total 15 subjects were
      selected. Six sets of maxillary casts were obtained. Face bow record was made
      using orbitale as anterior point of reference and the record was transferred to
      the Arcon and Non-Arcon articulator. The second and third mounting on Arcon and
      Non-Arcon articulator were done using Superior and inferior annular groove on
      incisal pin of articulator. Protrusive interocclusal records were made for all
      the subjects. Two lateral cephalograms one in maximum intercuspation and the
      other in protrusion for left and right side were taken. Anatomic condylar
      guidance of the subject were obtained from radiograph tracing. Arcon and Non
      arcon articulator were programmed with Protrusive interocclusal record of the
      subjects and the condylar guidance was tabulated for right and left side. The
      procedure was repeated for all three mountings for both the articulators.
      RESULTS: The orbitale is the best reference point which mounts maxillary cast
      closer to anatomic position. Inferior annular groove can also be used as anterior
      point of the reference. The superior annular groove is not recommended anterior
      point of reference.

PMID- 24015004
TI  - Acquired acid resistance of human enamel treated with laser (Er:YAG laser and Co2
      laser) and acidulated phosphate fluoride treatment: An in vitro atomic emission
      spectrometry analysis.
AB  - BACKGROUND: Dental caries is essentially a process of diffusion and dissolution.
      If the aspect of dissolution can be curtailed some degree of prevention can be
      achieved. AIMS: The present study was carried out to evaluate and compare the
      effect of Er:YAG laser and Co2 laser irradiation combined with acidulated
      phosphate fluoride treatment on in vitro acid resistance of human enamel. DESIGN:
      An in vitro study was carried out on 30 human premolars to evaluate the enamel's
      acid resistance using an atomic emission spectrometry analysis. MATERIALS AND
      METHODS: A total of 60 enamel specimens were prepared from 30 human premolars and
      were randomly assigned to 6 groups: (1) Untreated (control); (2) 1.23% acidulated
      phosphate fluoride (APF) gel application alone for 4 min; (3) Er:YAG laser
      treatment alone; (4) Co2 laser treatment alone; (5) Er:YAG laser + APF gel
      application; (6) Co2 laser + APF gel application. The specimens were then
      individually immersed in 5 ml of acetate buffer solution (0.1 mol/L, pH 4.5) and
      incubated at 37 degrees C for 24 h, and the acid resistance was evaluated by
      determining the calcium ion concentration using the atomic emission spectrometry.
      STATISTICAL ANALYSIS: An ANOVA model was constructed (P value of 0.05), followed
      by Tukey's test for multiple pair wise comparisons of mean values. RESULTS:
      Significant differences were found between the control group and the test groups
      (P < 0.001). CONCLUSIONS: Combining acidulated phosphate fluoride with either
      Er:YAG or Co2 laser had a synergistic effect in decreasing the enamel
      demineralization more than either fluoride treatment or laser treatment alone.

PMID- 24015005
TI  - A comparative evaluation of antioxidant enzymes and selenium in the serum of
      periodontitis patients with diabetes mellitus type 2.
AB  - CONTEXT: Chronic periodontitis is an inflammatory disease with an aberrant
      response characterized by exaggerated inflammation, involving the release of
      excess proteolytic enzymes and reactive oxygen species (ROS). Diabetes mellitus
      is a group of complex multisystem metabolic disorders characterized by a relative
      or absolute insufficiency of insulin secretion and or concomitant resistance to
      the metabolic action of insulin on target tissues. Increased production of ROS
      necessitates elevated requirements for the nutrients involved in antioxidant
      defenses: Selenium, zinc, and copper. Inflammatory states promote a decrease in
      the amount of systemic glutathione levels. Catalase is a central antioxidant
      enzyme constituting the primary defense against oxidative stress. AIMS: This
      study has been designed to evaluate the comparison of glutathione, catalase, and
      selenium levels in the serum of diabetes mellitus type 2 patients and healthy
      individuals with and without periodontal disease. SETTINGS AND DESIGN: This study
      is a case control study. MATERIALS AND METHODS: The study was designed as a case 
      control study comprising of 150 subjects, inclusive of both sexes and were
      divided into three groups of 50 patients each. Group I: 50 subjects with type 2
      diabetes mellitus and chronic periodontitis. Group II: 50 subjects who are
      systemically healthy with the chronic periodontitis. Group III: 50 subjects who
      are systemically healthy and not suffering from. PERIODONTITIS: Serum samples
      were taken for estimation of glutathione, catalase, and selenium from all groups,
      and Subjected to biochemical analysis after which atomic absorption
      spectrophotometry method was used to obtain their levels in serum. STATISTICAL
      ANALYSIS USED: ANOVA and Tukey HSD. RESULTS: The serum levels of glutathione in
      diabetic patients with periodontitis were significantly lower with a mean of
      61.36 + 8.054 when compared to healthy individuals with and without periodontitis
      with a mean of 56.93 + 6.874 and 90.36 + 6.564 respectively (P <= 0.005). The
      serum levels of catalase were significantly lower in diabetic patients with
      periodontitis with a mean of 19.30 + 7.355 when compared to healthy individuals
      with and without periodontitis with a mean of 20.71 + 6.472 and 36.09 + 5.108
      respectively (P <= 0.005). The serum levels of selenium were significantly lower
      in diabetic patients with periodontitis with a mean of 81.41 + 55.419 when
      compared to healthy individuals with and without periodontitis with a mean of
      161.44 + 84.787 and 193.84 + 66.713 respectively (P <= 0.005). CONCLUSIONS: The
      findings from the study suggest that the levels of glutathione, catalase, and
      selenium are significantly lower in diabetic patients with periodontitis and also
      in healthy individuals with periodontitis, but are highest in healthy controls,
      showing that the serum levels are inversely proportional to inflammation and
      tissue destruction.

PMID- 24015006
TI  - Demographic and clinical profile of oral lichen planus: A retrospective study.
AB  - INTRODUCTION: Oral lichen planus (OLP) is a relatively common inflammatory
      mucocutaneous disorder that frequently involves the oral mucosa. The clinical
      presentation of OLP ranges from mild painless white keratotic lesions to painful
      erosions and ulcerations. An important complication of OLP is the development of
      oral squamous cell carcinoma, which led the World Health Organization (WHO) to
      classify OLP as a potentially malignant disorder. The demographic and clinical
      characteristics of OLP have been well-described in several relatively large
      series from developed countries, whereas such series from developing countries
      are rare. OBJECTIVE: The objective of this retrospective study was to investigate
      the epidemiological and clinical characteristics of 128 OLP patients in rural
      population of India. MATERIALS AND METHODS: In this study, the diagnostic
      criteria proposed by van der Meij et al. in 2003 based on the WHO definition of
      OLP were used to identify cases. RESULTS: In 128 patients, M:F ratio was 1.61:1.
      The buccal mucosa was the most common site (88.20%). White lichen was seen in
      83.59% and red lichen in 16.40% cases. Reticular type of OLP was the most common
      form (83.5%) followed by erosive (15.6%) and atrophic OLP (0.78%). The incidence
      of systemic diseases included hypertension (11%), diabetes mellitus (2.4%), and
      hypothyroidism (0.78%). Histopathologically epithelial dysplasia was present in 4
      cases. CONCLUSION: Most of the characteristics are consistent with previous
      studies with differences in few. Lichen planus is a chronic disease where
      treatment is directed to control of symptoms. Long-term follow-up is essential to
      monitor for symptomatic flare ups and possible malignant transformation.

PMID- 24015007
TI  - Effectiveness of sub gingival irrigation of an indigenous 1% curcumin solution on
      clinical and microbiological parameters in chronic periodontitis patients: A
      pilot randomized clinical trial.
AB  - AIM: The aim of this study is to evaluate the efficacy of 1% curcumin (CU)
      solution and compare it with conventional irrigant i.e., 0.2% chlorhexidine (CHX)
      gluconate and a positive control (saline) as an adjunct to thorough scaling and
      root planing. MATERIALS AND METHODS: A total of 23 patients with non-adjacent
      probing pocket depths (PPDs) >=5mm were randomly assigned to CHX, CU and positive
      control irrigation groups and subjected to randomized single blinded clinical
      control trial. The clinical parameters bleeding on probing, redness, plaque
      index, PPD and microbiological parameter N-benzoyl-DL-arginine-2-naphthylamide
      (BANA) test were evaluated at baseline, 1, 3 and 6 months interval. RESULTS: At 1
      month evaluation, CU group showed better results compared with the other groups.
      However, by the end of the study period CHX group showed the best results with as
      light recurrence in the CU group. The results of BANA test showed similar results
      for both CU and CHX group throughout the study period. CONCLUSION: The results of
      this study show a mild to moderate beneficiary effect of CU irrigation when used
      as an adjunct to Scaling and root planing. Further studies may be required using
      varied concentrations of the drug to improve the substantivity of the drug and
      also to prevent early re-colonization of periodontal pathogens.

PMID- 24015008
TI  - Resistin in serum and gingival crevicular fluid as a marker of periodontal
      inflammation and its correlation with single-nucleotide polymorphism in human
      resistin gene at -420.
AB  - AIMS: Resistin is an adipocytokine, which have been studied for its role in
      insulin resistance and recently in inflammation. The aim of the present study is
      to assess the concentration of resistin in serum and gingival crevicular fluid
      (GCF) and to compare the levels between subjects with and without periodontitis
      and type 2 diabetes mellitus (T2DM) and to further correlate the resistin levels
      with the single-nucleotide polymorphism (SNP) at -420. SETTING AND DESIGNS: A
      total of 96 subjects (48 males and 48 females) were divided on the basis of
      gingival index (GI), probing pocket depth (PD), clinical attachment level (CAL)
      and hemoglobin A1c levels into healthy (group 1, n = 24), uncontrolled-diabetes
      related periodontitis (group 2, n = 24), controlled-diabetes related
      periodontitis (group 3, n = 24) and chronic periodontitis without T2DM (group 4,
      n = 24). MATERIALS AND METHODS: The GCF and serum levels of resistin were
      quantified using the enzyme-linked immunosorbent assay and compared among the
      study groups. Further, the association of the resistin levels with periodontal
      inflammation and SNP at -420 was studied. RESULTS AND CONCLUSION: The resistin
      levels in GCF and serum from patients with periodontitis or diabetes mellitus
      related periodontitis (controlled or uncontrolled) were higher than that of
      healthy subjects and correlated positively with GI. Further, subjects with GG
      genotype at -420 showed significantly higher GI, PD, CAL as compared with
      genotype group CC. Resistin was detected in all serum and GCF samples and was
      significantly higher in periodontitis. Further, GG genotype at -420 was
      associated significantly with periodontal inflammation and resistin levels.

PMID- 24015009
TI  - A comparative scanning electron microscopy study between hand instrument,
      ultrasonic scaling and erbium doped:Yttirum aluminum garnet laser on root
      surface: A morphological and thermal analysis.
AB  - BACKGROUND AND OBJECTIVES: Scaling and root planing is one of the most commonly
      used procedures for the treatment of periodontal diseases. Removal of calculus
      using conventional hand instruments is incomplete and rather time consuming. In
      search of more efficient and less difficult instrumentation, investigators have
      proposed lasers as an alternative or as adjuncts to scaling and root planing.
      Hence, the purpose of the present study was to evaluate the effectiveness of
      erbium doped: Yttirum aluminum garnet (Er:YAG) laser scaling and root planing
      alone or as an adjunct to hand and ultrasonic instrumentation. SUBJECTS AND
      METHODS: A total of 75 freshly extracted periodontally involved single rooted
      teeth were collected. Teeth were randomly divided into five treatment groups
      having 15 teeth each: Hand scaling only, ultrasonic scaling only, Er:YAG laser
      scaling only, hand scaling + Er:YAG laser scaling and ultrasonic scaling + Er:YAG
      laser scaling. Specimens were subjected to scanning electron microscopy and
      photographs were evaluated by three examiners who were blinded to the study.
      Parameters included were remaining calculus index, loss of tooth substance index,
      roughness loss of tooth substance index, presence or absence of smear layer,
      thermal damage and any other morphological damage. RESULTS: Er:YAG laser treated
      specimens showed similar effectiveness in calculus removal to the other test
      groups whereas tooth substance loss and tooth surface roughness was more on
      comparison with other groups. Ultrasonic treated specimens showed better results
      as compared to other groups with different parameters. However, smear layer
      presence was seen more with hand and ultrasonic groups. Very few laser treated
      specimens showed thermal damage and morphological change. INTERPRETATION AND
      CONCLUSION: In our study, ultrasonic scaling specimen have shown root surface
      clean and practically unaltered. On the other hand, hand instrument have produced
      a plane surface, but removed more tooth structure. The laser treated specimens
      showed rough surfaces without much residual deposit or any other sign of
      morphological change.

PMID- 24015010
TI  - Comparison of esthetic outcome after extraction or non-extraction orthodontic
      treatment in class II division 1 malocclusion patients.
AB  - INTRODUCTION: The extraction of premolars as a practical form of orthodontic
      therapy has been accepted for many years, but there remains a controversy
      regarding the effect of premolar extraction to improve esthetics as well as
      dentoskeletal relationship. The esthetic impact of the soft-tissue profile might
      play a major role in deciding on premolar extraction or non-extraction treatment,
      particularly in borderline patients. This cephalometric study was undertaken to
      compare the post-treatment soft-tissue profiles of successfully managed Class II,
      Division 1 malocclusions treated with either all first premolar extractions or
      treatment with a non-extraction therapy. MATERIALS AND METHODS: The sample
      consisted of 100 post-pubertal female patients of Class II Division I
      malocclusion. Group 1, treated with four first premolar extractions, consisted of
      50 female patients with a mean age of 14 years 1 month. Group 2, treated without
      extractions, consisted of 50 patients with a mean age of 13 years 5 months. Pre
      treatment and post-treatment lateral cephalometric radiographs were evaluated.
      The pre-treatment to post-treatment stage comparison and the intergroup
      comparison of the treatment changes were conducted between extraction and non
      extraction groups of Class II malocclusion samples with t-tests. RESULTS: The
      soft-tissue facial profiles of the extraction and non-extraction samples were the
      same following active treatment except for a more retruded lower lip and a more
      pronounced lower labial sulcus in those patients subjected to extraction.
      CONCLUSIONS: The extraction or non-extraction decision, if based on sound
      diagnostic criteria, seems to have no systematic detrimental effects on the
      facial profile.

PMID- 24015011
TI  - The effect of using different rinsing angles on the micro-tensile bond strength
      of the sealant to the etched enamel.
AB  - BACKGROUND AND OBJECTIVES: Attempts to enhance bond strength of the sealant have
      been among the most important sides of dental research. The purpose of the
      present study was to evaluate the effect of using different rinsing angles on the
      micro-tensile bond strength of the sealant to the etched enamel. MATERIALS AND
      METHODS: Sixty first-premolars were randomly assigned to six groups based on the
      rinsing angle applied (15 degrees , 30 degrees , 45 degrees , 60 degrees , 75
      degrees  and 90 degrees ). Following etching and rinsing, a 4-mm height build-up
      of sealant material was created. Bonded specimens were sectioned into sticks (1
      mm * 1 mm), which were subjected to micro-tensile bond strength, testing at a
      cross head speed of 0.5 mm/min. STATISTICAL ANALYSIS USED: The data were analyzed
      by Kolmogorov-Smirnov and post-hoc Tukey test. RESULTS: The tensile bond strength
      in specimens rinsed at 90 degrees  were statistically higher compared to those
      rinsed at 15 degrees  and 30 degrees  (P < 0.05) and increasing the angle from 15
      degrees  to 90 degrees  was correlated with a reduction in the number of
      specimens with adhesive failures. CONCLUSIONS: Rinsing the conditioned enamel
      surface at 90 degrees  may improve the bond strength and retention of the
      sealant.

PMID- 24015012
TI  - Abberantly placed impacted mandibular canine.
AB  - Pre-eruptive migration of a tooth across the midline is termed as transmigration.
      It is believed that transmigration is rare and unique to the mandibular permanent
      canines, and even more rarely reported for others. Transmigration is a phenomenon
      of yet unknown etiology. It follows the direction of its long axis, with the
      crown leading the migration. The tendency of a canine to cross the barrier of
      mandibular midline suture is a more important consideration than the distance of
      migration after crossing the midline. Here we present one new case of aberrantly
      positioned right mandibular canine which has undergone migration and was
      accidently found on radiological examination before orthodontic treatment. Once
      diagnosed an aberrantly positioned impacted canine requires surgical removal. 

PMID- 24015013
TI  - Recurrent ameloblastoma in temporal fossa: A diagnostic dilemma.
AB  - Ameloblastoma is a unique, histologically benign but aggressive neoplasm of the
      jaws, arising from odontogenic epithelium with potency to cause extensive
      destruction of jaw bones and infiltration into the surrounding tissues.
      Recurrences are common after incomplete treatment. Recurrences can occur at
      difficult sites such as temporal and infratemporal fossa, orbit, anterior cranial
      base, paranasal sinuses etc. Fine needle aspiration cytology or core biopsy of
      these recurrent lesions may be misleading. Clinical course and radiological
      features help immensely in these situations. Good communication between surgeon,
      radiologist, and pathologist is of paramount importance. 

PMID- 24015014
TI  - Management of anterior dental crossbite with removable appliances.
AB  - This case report describes the treatment of an 8-year-old girl with anterior
      dental crossbite using a series of removable appliances to bring the teeth into a
      normal position. CLINICAL PRESENTATION AND INTERVENTION: A removable acrylic
      appliance with a bite plate incorporating a screw was used to correct the
      anterior dental crossbite and align the incisors. The subsequent eruption of the
      maxillary left lateral incisor on the palatinal side was treated with a second
      acrylic plate incorporating a labiolingual spring. After an 8-month period, the
      anterior crossbite involving multiple incisors was corrected.

PMID- 24015015
TI  - Paget disease of bone: A classic case report.
AB  - Paget disease of bone (PDB) is a chronic progressive disease of the bone of
      uncertain etiology, characterized initially by an increase in bone resorption,
      followed by a disorganized and excessive formation of bone, leading to pain,
      fractures, and deformities. It can manifest as a monostotic or polyostotic
      disease. The prevalence of PDB is common in the Anglo-Saxon population, but
      relatively rare in India. The disease is often asymptomatic and commonly seen in
      an aging population. The diagnosis of the disease is mostly based on radiological
      examination and on biochemical markers of bone turnover. Markedly elevated serum
      alkaline phosphatase (SAP) is a constant feature while calcium and phosphate
      levels are typically within normal limits. It is being successfully treated by
      biphosphonates, a group of anti-resorptive drugs, thereby decreasing the
      morbidity and mortality associated with the disease. We report a classic case of
      PDB with craniofacial involvement resulting in Leontiasis Ossea (lion like face),
      cotton wool appearance of the skull and elevated SAP. 

PMID- 24015016
TI  - Full mouth rehabilitation of a patient with mandibular implant screw retained Fp
      3 prosthesis opposing maxillary acrylic removable over-denture.
AB  - A hybrid denture is one that is fabricated over a metal framework and retained by
      screws threaded into the implant abutments. The anterior part of a mandibular
      hybrid denture is fixed on implants while the posterior part of the denture is
      extended and cantilevered from implants. This article presents the fabrication of
      a maxillary over-denture opposing mandibular implant retained hybrid prosthesis.
      A total of four implants were placed in the mandibular arch. Castable abutments
      were used to produce the optimal angulations. Framework was waxed, cast
      recovered, and the fit was refined until the framework seated passively on the
      master cast. The mandibular denture teeth were waxed to the hybrid framework, and
      a final wax try-in was performed to verify and correct maxillomandibular
      relations before processing. The prosthesis was inserted after verification of
      occlusion, retention, and stability. The rehabilitation of edentulous patients
      with hybrid dentures has been observed to achieve greater masticatory function
      and psychological satisfaction than with conventional over-dentures. Producing a
      passive-fitting substructure for a fixed removable screw retained hybrid
      prosthesis is arguably one of the most technically complex tasks in implant
      dentistry. The technique presented may not initially produce a perfectly passive
      framework, but use of disclosing media and adjusting the internal aspect of the
      casting can result in non-binding, fully seated prostheses. 

PMID- 24015017
TI  - Deep vein thrombosis: A rare complication in oral and maxillofacial surgery: A
      review of two cases.
AB  - Deep vein thrombosis (DVT) is caused by obstruction of blood flow of deep veins
      in upper and lower limb. One of the precipitating factors for DVT is surgery
      under general anesthesia exceeding 30 min. However, there are very few reports of
      DVT associated with surgery of oral and maxillofacial region. In this paper we
      report two cases of DVT involving left ilio-femoropopliteal deep vein in one
      patient treated for fractured left angle of mandible and left peroneal vein in
      the other patient treated for oral sub mucous fibrosis. Clinical and color
      Doppler examination were performed to diagnose the condition and were referred to
      vascular surgical unit of higher institute for further management. These cases
      illustrates any surgery of maxillofacial region is not free from risk of DVT,
      which can cause fatal pulmonary thromboembolism. 

PMID- 24015018
TI  - Intraosseous adenoid cystic carcinoma of maxilla: A rare case report.
AB  - Adenoid cystic carcinoma (ACC) accounts for approximately 6-10% of all salivary
      gland tumors. Palatal minor salivary glands, parotid, and sub-mandibular glands
      are usually affected. Rarely, these lesions arising intraosseously have been
      reported. Mandible is commonly involved than maxilla. The present case is a giant
      ACC involving the right maxilla. A thorough clinical and radiographic evaluation
      was performed to assess the involvement of surrounding vital structures along
      with a meticulous metastatic work-up. Computed tomography showed a giant lesion
      in maxilla encroaching the left nasal fossa, antrum, buccal space, and oral
      cavity. No metastasis was noted. Histological evaluation from multiple sites
      showed both cribriform and solid patterns. Radiotherapy was given as patient did
      not comply for surgery. Though central ACC is extremely rare, especially in
      maxilla, it should be included in the differentials for lesions in maxilla. A
      prompt diagnosis with treatment and long-term follow-up is advised in such cases.

PMID- 24015019
TI  - Forced orthodontic eruption for augmentation of soft and hard tissue prior to
      implant placement.
AB  - Forced orthodontic eruption (FOE) is a non-surgical treatment option that allows
      modifying the osseous and gingival topography. The aim of this article is to
      present a clinical case of a FOE, which resulted in an improvement of the amount
      of available bone and soft-tissues for implant site development. Patient was
      referred for treatment of mobility and unesthetic appearance of their maxillary
      incisors. Clinical and radiographic examination revealed inflamed gingival
      tissue, horizontal and vertical tooth mobility and interproximal angular bone
      defects. It was chosen a multidisciplinary treatment approach using FOE, tooth
      extraction, and immediate implant placement to achieve better esthetic results.
      The use of FOE, in periodontally compromised teeth, promoted the formation of a
      new bone and soft-tissue in a coronal direction, without additional surgical
      procedures, enabling an esthetic, and functional implant-supported restoration. 

PMID- 24015020
TI  - Facial pain due to elongated styloid process.
AB  - Pain is the most frequent cause of suffering and disability. The etiology of
      orofacial pain is still elusive. However, the etiology has to be ascertained for
      definitive treatment. Only after a systematic and careful evaluation can a
      treating surgeon be aware of the underlying cause. Though dental causes
      predominate in the diagnosis of orofacial pain, the rare cause of facial pain
      have to be excluded, which would prevent unnecessary and fruitless dental
      treatment. The present case is an example of a rare condition that may be
      overlooked during examination. This paper will describe a case of vague
      unilateral orofacial pain, the diagnosis of which zeroed down to an elongated
      styloid process. 

PMID- 24015021
TI  - Osteoradionecrosis of mandible: Case report with review of literature.
AB  - Osteoradionecrosis (ORN) of the jaws, particularly of the mandible, is a long
      term and serious complication of therapeutic radiotherapy for head and neck
      cancer. The mandible is affected more commonly than any other bones of the head
      and neck region. The incidence of ORN of mandible is reported to be between 2%
      and 22%. With the older radiation techniques, the rate of ORN was reported to be
      between 5% and 15%, whereas with newer techniques such as 3D conformal therapy
      and intensity modulated radiotherapy the rate of ORN has decreased to 6% or less.
      We here report a case of mandibular ORN and the literature review discusses the
      clinical features, pathogenesis, preventive measures, and management of ORN. 

PMID- 24015022
TI  - Filariasis of the buccal mucosa: A diagnostic dilemma.
AB  - Filariasis is an endemic disease in tropical and subtropical countries. Filarial
      nematodes can infect humans through vectors, commonly mosquitoes. Human infection
      can manifest as lymphatic filariasis, subcutaneous or pulmonary nodules and with
      eye involvement. Intra-oral presentation is very rare and often poses a
      diagnostic dilemma to the dentist. We report a case of intra-oral Dirofilaria
      repens infection in a 54-year-old female patient, involving the buccal mucosa.
      History was unremarkable and on clinical examination, a diffuse swelling with no
      significant signs and symptoms was seen. Laboratory investigations and
      radiographs were non-contributory to diagnosis. Ultrasound findings revealed a
      hypo-echoic lesion in the muscular layer of the left cheek. Differential
      diagnoses considered were minor salivary gland tumor, parotid sialolith, and
      cysticercosis among others. The presence of a Dirofilaria worm in the excised
      nodule confirmed the diagnosis. Medical awareness of the risk of intra-oral
      nematode infection is essential. A detailed travel history, awareness of endemic
      status of certain diseases, proper diagnosis and management helps in better
      prognosis for the patient. 

PMID- 24015023
TI  - Oral proliferative verrucous leukoplakia: A case report with an update.
AB  - White lesions both physiologic as well as pathologic are relatively frequent in
      the oral cavity, the most common pathology being oral leukoplakia (OL). There are
      many variants of OL, one of which is oral proliferative verrucous leukoplakia
      (OPVL). OPVL is a rare clinico-pathological entity, which is slow growing, long
      term progressive lesion, but remains an enigmatic and difficult to define. The
      etiology of OPVL remains still unclear. Tobacco use does not seem to have a
      significant influence on the appearance of OPVL. These lesions may occur both in
      smokers and non-smokers. It is observed more frequently in women and elderly
      patients over 60 years at the time of diagnosis. The buccal mucosa and tongue are
      the most frequently involved sites. It develops initially as a white plaque of
      hyperkeratosis that eventually becomes a multifocal disease with confluent,
      exophytic and proliferative features. Various published case series have
      presented OPVL as a disease with aggressive biological behavior due to its high
      probability of recurrence and a high rate of malignant transformation. Prognosis
      is poor for this seemingly harmless-appearing white lesion of the oral mucosa.
      This article describes the clinical aspects and histologic features of an OPVL
      case that demonstrated the typical behavior pattern in a long-standing,
      persistent lesion and discusses this relatively rare entity in light of current
      information. 

PMID- 24015024
TI  - Triple tooth in primary dentition: A proposed classification.
AB  - Triple teeth may result from fusion, gemination or concrescence causing transient
      esthetic and functional problems in primary dentition and retardation or
      alteration of development and eruption of permanent successors. We report an
      unusual case of a boy aged five with fusion among maxillary left primary central
      incisor, lateral incisor and a supernumerary tooth concomitant with agenesis of
      permanent lateral incisor. A review of literature on triple tooth was done along
      with a proposed classification of the triple teeth. 

PMID- 24015025
TI  - Maturogenesis of non-vital immature permanent teeth.
AB  - Pulpal necrosis in young permanent teeth often results in teeth with open apex,
      thin root walls and poor crown root ratio. Out of the available treatment options
      maturogenesis has been the most conservative option that exploits full potential
      of pulp for dentin deposition. Maturogenesis involves disinfecting the root canal
      system followed by stimulation of blood clot from the periapical tissue, which
      provides a matrix into which the cell could grow and sealing the coronal excess.
      In the present case report, tri antibacterial paste (3 Mix) was used as an
      intracanal medicament that proved successful in stimulating vital pulp cells of
      the periapical region for maturogenesis. Five months radiograph follow-up showed
      thickening of lateral dentinal walls, which progress until 15 months resulting in
      apical closure, thickening of lateral dentinal walls and increase root length. 

PMID- 24015026
TI  - Orthodontic movement of a maxillary central incisor with a horizontal root
      fracture treated using an intra-radicular fibre splint.
AB  - This paper reports the case of a 15-year-old boy with a horizontal root fracture
      in the left maxillary central incisor along with class II division 1 malocclusion
      for whom a fixed orthodontic treatment was planned. The fracture was present at
      the junction of apical and middle-third as a result of trauma 2 years back. No
      splinting was carried out at that time and the tooth was found to be vital,
      asymptomatic and showed a type-1 repair pattern. An intentional root canal
      treatment was carried out for placement of an intra-radicular fiber splint,
      nearly 3 mm beyond the fracture line. Orthodontic treatment was initiated after a
      month; to which the fractured and splinted tooth responded successfully. This
      report highlights the successful use of an intra-radicular splint for
      horizontally fractured tooth requiring orthodontic treatment. 

PMID- 24015027
TI  - Shock-induced collapse of a bubble inside a deformable vessel.
AB  - Shockwave lithotripsy repeatedly focuses shockwaves on kidney stones to induce
      their fracture, partially through cavitation erosion. A typical side effect of
      the procedure is hemorrhage, which is potentially the result of the growth and
      collapse of bubbles inside blood vessels. To identify the mechanisms by which
      shock-induced collapse could lead to the onset of injury, we study an idealized
      problem involving a preexisting bubble in a deformable vessel. We utilize a high
      order accurate, shock- and interface-capturing, finite-volume scheme and simulate
      the three-dimensional shock-induced collapse of an air bubble immersed in a
      cylindrical water column which is embedded in a gelatin/water mixture. The
      mixture is a soft tissue simulant, 10% gelatin by weight, and is modeled by the
      stiffened gas equation of state. The bubble dynamics of this model configuration
      are characterized by the collapse of the bubble and its subsequent jetting in the
      direction of the propagation of the shockwave. The vessel wall, which is defined
      by the material interface between the water and gelatin/water mixture, is
      invaginated by the collapse and distended by the impact of the jet. The present
      results show that the highest measured pressures and deformations occur when the
      volumetric confinement of the bubble is strongest, the bubble is nearest the
      vessel wall and/or the angle of incidence of the shockwave reduces the distance
      between the jet tip and the nearest vessel surface. For a particular case
      considered, the 40 MPa shockwave utilized in this study to collapse the bubble
      generated a vessel wall pressure of almost 450 MPa and produced both an
      invagination and distention of nearly 50% of the initial vessel radius on a
      ??(10) ns timescale. These results are indicative of the significant potential of
      shock-induced collapse to contribute to the injury of blood vessels in shockwave
      lithotripsy.

PMID- 24015028
TI  - Intraoperative neurophysiologic monitoring: basic principles and recent update.
AB  - The recent developments of new devices and advances in anesthesiology have
      greatly improved the utility and accuracy of intraoperative neurophysiological
      monitoring (IOM). Herein, we review the basic principles of the
      electrophysiological methods employed under IOM in the operating room. These
      include motor evoked potentials, somatosensory evoked potentials,
      electroencephalography, electromyography, brainstem auditory evoked potentials,
      and visual evoked potentials. Most of these techniques have certain limitations
      and their utility is still being debated. In this review, we also discuss the
      optimal stimulation/recording method for each of these modalities during
      individual surgeries as well as the diverse criteria for alarm signs. 

PMID- 24015029
TI  - Multidisciplinary bibliographic databases.

PMID- 24015030
TI  - Mortality of community-acquired pneumonia in Korea: assessed with the pneumonia
      severity index and the CURB-65 score.
AB  - The pneumonia severity index (PSI) and CURB-65 are widely used tools for the
      prediction of community-acquired pneumonia (CAP). This study was conducted to
      evaluate validation of severity scoring system including the PSI and CURB-65
      scores of Korean CAP patients. In the prospective CAP cohort (participated in by
      14 hospitals in Korea from January 2009 to September 2011), 883 patients aged
      over 18 yr were studied. The 30-day mortalities of all patients were calculated
      with their PSI index classes and CURB scores. The overall mortality rate was 4.5%
      (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3%
      (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88);
      score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class
      were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5%
      (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP
      patients varies based on the severity scores and CURB-65 is more valid for the
      lower scores, and PSI, for the higher scores. Thus, these variations must be
      considered when using PSI and CURB-65 for CAP in Korean patients. 

PMID- 24015031
TI  - Comparative estimation of coverage between national immunization program vaccines
      and non-NIP vaccines in Korea.
AB  - This study aimed to describe the differences in vaccination coverage between
      National Immunization Program (NIP) vaccines and non-NIP vaccines in Korea and to
      identify factors affecting the difference. Nationwide face-to-face interview
      based questionnaire survey among randomly selected 4,374 participants aged 7-83
      months was conducted. Vaccination coverage analyzed according to the birth
      cohorts, geographic areas, and socio-demographic characteristics. We found that
      NIP vaccines recorded higher primary vaccination coverage compared to non-NIP
      vaccines (95.9%-100% vs 30.7%-85.4%). The highest rate was Haemophilus influenzae
      type b (Hib) vaccine (85.4%), which was introduced in 1996, and the lowest rate
      was rotavirus vaccine (30.7%), which was introduced recently. On multivariate
      analysis, having a sibling were significantly associated with lower uptake of Hib
      vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine; while,
      older mother's age and attendance to daycare center were significantly associated
      with lower uptake of PCV and rotavirus vaccine (P < 0.001). We found differences
      in the vaccine coverage rate between NIP vaccines and non-NIP vaccines; and the
      data suggests potential disparity in accessing non-NIP vaccines in Korea.
      Expansion of NIP to include non-NIP vaccines can provide better protection
      against the diseases through increased coverage. 

PMID- 24015032
TI  - Caspase-1 level in synovial fluid is high in patients with spondyloarthropathy
      but not in patients with gout.
AB  - Activation of caspase-1 by NALP3 inflammasomes has been shown to be important in
      initiating acute gouty arthritis. The objectives of this study were to measure
      the levels of caspase-1 in synovial fluid in gout and various arthritides, and to
      elucidate the clinical significance of caspase-1 levels in synovial fluid.
      Caspase-1, IL-1beta, IL-18, and uric acid were measured in synovial fluid from
      112 patients with gout and other arthritides, such as rheumatoid arthritis,
      osteoarthritis, and spondyloarthropathy. Caspase-1 in synovial fluid from
      patients with crystal-induced arthritis, inflammatory arthritis, osteoarthritis,
      and spondyloarthropathy was 35.9 +/- 86.7, 49.7 +/- 107.7, 2.1 +/- 7.0, and 152.6
      +/- 155.7 pg/mL, respectively. The mean level and the frequency of high levels
      (>=125 pg/mL) of caspase-1 in spondyloarthropathy were significantly higher than
      those in the other arthritides including gout. Caspase-1 was detectible in the
      synovial fluid of patients with the various arthritides. Contrary to our
      hypothesis, the caspase-1 level in the synovial fluid of patients with gout was
      not higher than in that of other arthritides. High levels of caspase-1 may be
      helpful in differentiating spondyloarthropathy from other arthritides. 

PMID- 24015033
TI  - Podoplanin, alpha-smooth muscle actin or S100A4 expressing cancer-associated
      fibroblasts are associated with different prognosis in colorectal cancers.
AB  - The interactions between the tumor microenvironment and tumor cells determine the
      behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have
      a tumor progressive or a protective role likely depends on the type of tumor
      cells and the CAF subpopulation. In the present study, we analyzed the prognostic
      significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes
      were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN),
      alpha-smooth muscle actin (alpha-SMA), and S100A4. The relationship between the
      CAF phenotypes and 11 clinicopathological parameters were evaluated and their
      prognostic significance was analyzed from the disease-free and overall survival
      times. We observed that at the tumor invasive front, PDPN CAFs were present in
      40% of the cases, and S100A4 or alpha-SMA CAFs were detected in all the cases.
      PDPN/S100A4 and alpha-SMA/S100A4 dual-stained CAFs were observed in 10% and 40%
      of the cases, respectively. The PDPN(+) CAFs were associated with 6 favorable
      clinicopathological parameters and prolonged disease-free survival time. The
      PDPN(-)/alpha-SMA(high) CAFs were associated with 6 aggressive
      clinicopathological parameters and tended to exhibit shorter disease-free
      survival time. On the other hand, the PDPN(-)/S100A4(high) CAFs were associated
      with 2 tumor progression parameters, but not with disease prognosis. The PDPN(+)
      CAF phenotype is distinct from the alpha-SMA or S100A4 CAFs in that it is
      associated with less aggressive tumors and a favorable prognosis, whereas the
      PDPN(-)/alpha-SMA(high) or PDPN(-)/S100A4(high) CAFs are associated with tumor
      progression in CRC. These findings suggest that CAFs can be a useful prognostic
      biomarker or potential targets of anti-cancer therapy in CRC. 

PMID- 24015034
TI  - Impact of interleukin-10 gene polymorphisms on survival in patients with
      colorectal cancer.
AB  - Chronic inflammation is thought to be the leading cause of colorectal cancer, and
      interleukin-10 (IL10) has been identified as a potent immunomodulatory cytokine
      that regulates inflammatory responses in the gastrointestinal tract. Although
      several single nucleotide polymorphisms (SNPs) in IL10 have been associated with
      the risk of colorectal cancer, their prognostic significance has not been
      determined. Two hundred and eighty-two colorectal cancer patients were genotyped
      for two candidate cancer-associated SNPs in IL10. The associations of these SNPs
      with distant metastasis-free survival and overall survival were evaluated by
      Kaplan-Meier analysis and Cox regression model. The minor homozygote GG genotype
      of IL10 rs3021094 was significantly associated with a 3.30-fold higher risk of
      death compared with the TT+TG genotypes (P=0.011). The patients with IL10
      rs3021094 GG genotype also had a poorer overall survival in Kaplan-Meier analysis
      (log-rank P=0.007) and in multivariate Cox regression model (P=0.044) adjusting
      for age, gender, carcinoembryonic antigen levels, tumor differentiation, stage,
      lymphovascular invasion, and perineural invasion. In conclusion, our results
      suggest that IL10 rs3021094 might be a valuable prognostic biomarker for
      colorectal cancer patients. 

PMID- 24015035
TI  - The impact of vascular access for in-hospital major bleeding in patients with
      acute coronary syndrome at moderate- to very high-bleeding risk.
AB  - The aim of our study was to determine the impact of vascular access on in
      hospital major bleeding (IHMB) in acute coronary syndrome (ACS). We analyzed 995
      patients with non-ST elevation myocardial infarction and unstable angina at the
      Can Rapid risk stratification of Unstable angina patients Suppress ADverse
      outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) moderate-
      to very high-bleeding risk scores in trans-radial intervention (TRI)
      retrospective registry from 16 centers in Korea. A total of 402 patients received
      TRI and 593 patients did trans-femoral intervention (TFI). The primary end-point
      was IHMB as defined in the CRUSADE. There were no significant differences in in
      hospital and 1-yr mortality rates between two groups. However, TRI had lower
      incidences of IHMB and blood transfusion than TFI (6.0% vs 9.4%, P = 0.048; 4.5%
      vs 9.4%, P = 0.003). The patients suffered from IHMB had higher incidences of in
      hospital and 1-yr mortality than those free from IHMB (3.1% vs 15.0%, P < 0.001;
      7.2% vs 30.0%, P < 0.001). TRI was an independent negative predictor of IHMB
      (odds ratio, 0.305; 95% confidence interval, 0.109-0.851; P = 0.003). In
      conclusions, IHMB is still significantly correlated with in-hospital and 1-yr
      mortality. Our study suggests that compared to TFI, TRI could reduce IHMB in
      patients with ACS at moderate- to very high-bleeding risk. 

PMID- 24015036
TI  - Hemoglobin concentration and risk of cardiovascular disease in Korean men and
      women - the Korean heart study.
AB  - This study investigated the relationship between hemoglobin concentration and the
      incidence of cardiovascular diseases (CVD). A total of 407,858 subjects (256,851
      men, aged 30-94 yr), who underwent physical examination at 17 Korean nationwide
      health examination centers, was included in this study. Data regarding CVD
      incidence were obtained from the Korean National Health Insurance database. In
      Cox proportional hazard models, men with lower or higher hemoglobin level showed
      higher hazard ratios (HR) with total CVD (HR, 1.14; 95% Confidence interval [CI],
      1.08-1.21 for the 1st quintile; HR, 1.14; 95% CI, 1.09-1.21 for the 5th
      quintile), ischemic heart disease (HR, 1.16; 95% CI, 1.07-1.26 for the 1st
      quintile; HR, 1.16; 95% CI, 1.07-1.25 for the 5th quintile), and stroke (HR,
      1.13; 95% CI, 1.02-1.25 for the 1st quintile; HR, 1.18; 95% CI, 1.07-1.30 for the
      5th quintile) compared to those with mid-level of hemoglobin (3rd quintile).
      Women with higher hemoglobin level showed higher HR with total CVD (HR, 1.15; 95%
      CI, 1.01-1.31 for pre-menopausal women; HR, 1.08; 95% CI, 1.01-1.16 for post
      menopausal women). We found an independent U-shaped association between
      hemoglobin level and CVD incidence in Korean population. 

PMID- 24015037
TI  - Complication rate of transfemoral endomyocardial biopsy with fluoroscopic and two
      dimensional echocardiographic guidance: a 10-year experience of 228 consecutive
      procedures.
AB  - Endomyocardial biopsy (EMB) is one of the reliable methods for the diagnosis of
      various cardiac diseases. However, EMB can cause various complications. The
      purpose of this study is to evaluate the complication of transfemoral EMB with
      both fluoroscopic and two-dimensional (2-D) echocardiographic guidance. A total
      of 228 patients (148 men; 46.0+/-14.6 yr-old) who underwent EMB at Kyungpook
      National University Hospital from January 2002 to June 2012 were included. EMB
      was performed via the right femoral approach with the guidance of both
      echocardiography and fluoroscopy. Overall, EMB-related complications occurred in
      21 patients (9.2%) including one case (0.4%) with cardiac tamponade requiring
      emergent pericardiocentesis, four cases (1.8%) with small pericardial effusion
      without pericardiocentesis, two cases (0.9%) with hemodynamically unstable
      ventricular tachycardia (VT), one case (0.4%) with nonsustained VT, one case
      (0.4%) with tricuspid regurgitation, twelve cases (5.3%) with right bundle branch
      block. There was no occurrence of either EMB-related death or cardiac surgery.
      Left ventricular ejection fraction was significantly lower (32.0+/-18.7% vs
      42.0+/-19.1%, P=0.023) and left ventricular end-diastolic dimension was larger
      (60.0+/-10.0 mm vs 54.2+/-10.2 mm, P=0.013) in patients with EMB related
      complications than in those without. It is concluded that transfemoral EMB with
      fluoroscopic and 2-D echocardiographic guidance is a safe procedure with low
      complication rate. 

PMID- 24015038
TI  - Association of polymorphisms in the vitamin D receptor promoter with idiopathic
      short stature.
AB  - The genetic alterations of vitamin D receptor (VDR) are related with the growth
      of long bone. There were a lot of reports regarding an association of
      polymorphisms in the VDR promoter with many disorders, but not with idiopathic
      short stature (ISS). We investigated the association of them with ISS. A total of
      50 subjects, including 29 ISS patients and 21 healthy controls with their heights
      within the normal range was recruited. We selected two single nucleotide
      polymorphisms (SNPs) from VDR promoter (rs11568820 at the Cdx-2 binding site
      upstream of exon 1e and rs4516035 at -1012 upstream of exon 1a) as candidates,
      respectively. In genotype analysis, the frequency of A/A genotype at the Cdx-2
      binding site locus (rs11568820) upstream of exon 1e of VDR was decreased to 6.9%
      in ISS patients (28.6% in controls) (P = 0.027). The genetic variation at the Cdx
      2 binding site of VDR promoter can be a contributing factor of growth of height. 

PMID- 24015039
TI  - Sleep duration and glycemic control in patients with diabetes mellitus: Korea
      National Health and Nutrition Examination Survey 2007-2010.
AB  - Short sleep duration has been reported to increase the risk of diabetes. However,
      the influence of sleep duration on glycemic control in diabetic patients has not
      been clarified. In this study we evaluated the association between sleep duration
      and glycemic control in diabetic patients. We analyzed the data from the Korea
      National Health and Nutrition Examination Survey (KNHANES) 2007-2010. Sleep
      duration was classified into five groups: <6, 6, 7, 8, and >=9 h/day. Fasting
      blood glucose and HbA1c showed a U-shaped trend according to sleep duration.
      Sleep duration of 7 h/day had the lowest HbA1c (7.26%) among the subjects
      (P=0.026). In the older age group (>=65 yr), a sleep duration of 6 h/day was
      associated with the lowest HbA1c (7.26%). The adjusted odds ratio (OR) with a 95%
      confidence interval (CI) of worse glycemic control (HbA1c >=7.0%) in group of
      sleep duration of >=9 h/day was 1.48 (1.04-2.13) compared with the group of 7
      h/day. This relationship disappeared after adjusting duration of diabetes (OR,
      1.38; 95% CI, 0.93-2.03). Our results suggest that sleep duration and glycemic
      control in diabetic patients has U-shaped relationship which was mainly affected
      by duration of diabetes. 

PMID- 24015040
TI  - The clinical measures associated with C-peptide decline in patients with type 1
      diabetes over 15 years.
AB  - This study was done to characterize the natural course of C-peptide levels in
      patients with type 1 diabetes and identify distinguishing characters among
      patients with lower rates of C-peptide decline. A sample of 95 children with type
      1 diabetes was analyzed to retrospectively track serum levels of C-peptide,
      HbA1c, weight, BMI, and diabetic complications for the 15 yr after diagnosis. The
      clinical characteristics were compared between the patients with low and high C
      peptide levels, respectively. The average C-peptide level among all patients was
      significantly reduced five years after diagnosis (P < 0.001). The incidence of
      diabetic ketoacidosis was significantly lower among the patients with high levels
      of C-peptide (P = 0.038). The body weight and BMI standard deviation scores (SDS)
      15 yr after diagnosis were significantly higher among the patients with low C
      peptide levels (weight SDS, P = 0.012; BMI SDS, P = 0.044). In conclusion, C
      peptide level was significantly decreased after 5 yr from diagnosis. Type 1
      diabetes patients whose beta-cell functions were preserved might have low
      incidence of diabetic ketoacidosis. The declines of C-peptide level after
      diagnosis in type 1 diabetes may be associated with changes of body weight and
      BMI. 

PMID- 24015041
TI  - Factors predictive of high-risk adenomas at the third colonoscopy after initial
      adenoma removal.
AB  - Evaluating predictive factors for high-risk adenomas at the third colonoscopy
      based on two prior colonoscopies may help evaluate high-risk adenoma at the third
      colonoscopy. We analyzed clinical data of 131 patients at Severance Hospital from
      January 1997 to January 2011. All of them underwent two subsequent colonoscopies
      after removal of adenomas during an initial colonoscopy. Among 20 patients with
      high-risk adenoma at the first and second colonoscopies, 10 (50%) patients had
      high-risk adenoma at the third colonoscopy. Among the 67 patients who had high
      risk adenoma only once at the first or second colonoscopy, 15 (22.4%) patients
      had high-risk adenoma at the third colonoscopy but among the 44 patients without
      high-risk adenoma at the first and second colonoscopies, only 1 (2.3%) patient
      had high-risk adenoma at the third colonoscopy (P < 0.001). A multivariate time
      dependent covariate Cox regression analysis confirmed that high-risk adenoma at
      the first and/or second colonoscopy (HR, 9.56; 95% CI, 2.37-38.54; P = 0.002) was
      independent predictor of high-risk adenoma at the third colonoscopy. Given these
      findings, data from two prior colonoscopies, not one prior examination, may help
      identify high-risk populations at the third colonoscopy who require careful
      colonoscopic surveillance. 

PMID- 24015042
TI  - Influence of body mass index on the growth hormone response to provocative
      testing in short children without growth hormone deficiency.
AB  - Obesity and its related factors are known to suppress the secretion of growth
      hormone (GH). We aimed to evaluate the influence of body mass index (BMI) on the
      peak GH response to provocative testing in short children without GH deficiency.
      We conducted a retrospective review of medical records of 88 children (2-15 yr
      old) whose height was less than 3 percentile for one's age and sex, with normal
      results (peak GH level > 10 ng/mL) of GH provocative testing with clonidine and
      dopamine. Peak stimulated GH level, height, weight, pubertal status and serum IGF
      1 level were measured. Univariate analysis showed that the BMI standard deviation
      score (SDS) correlated negatively with the natural log (ln) of the peak
      stimulated GH level (ln peak GH). BMI SDS did not correlate significantly with
      sex, age, pubertal status, or ln IGF-1 level. BMI SDS correlated negatively with
      ln peak GH level induced by clonidine but not by dopamine. In stepwise
      multivariate regression analysis, BMI SDS was the only significant predictor of
      ln peak GH level in the combination of tests and the clonidine test, but not in
      the dopamine test. In children without GH deficiency, BMI SDS correlates
      negatively with the peak GH level. BMI SDS should be included in the analysis of
      the results of GH provocation tests, especially tests with clonidine. 

PMID- 24015043
TI  - Prevalence, clinical characteristics, and management of functional constipation
      at pediatric gastroenterology clinics.
AB  - The purpose of this study was to investigate the prevalence, clinical
      characteristics, and management of functional constipation at pediatric
      gastroenterology clinics. A prospective survey using the Rome III criteria was
      distributed to a group of parents of children with a constipation history and its
      control group in May 2008. The mean prevalence of constipation was 6.4%, which
      was similar to those in other countries. Statistically significant variables for
      children without constipation were that more children had a body mass index of
      below the 10th percentile even though they received more mother's care and ate
      balanced meals compared to the constipation group. Meanwhile, the constipation
      group frequently showed a history of constipation in infancy, picky-eating, lack
      of exercise, and retentive posturing. When analyzed with the Rome III criteria,
      the children showed greater than 60% rate of hard stools, painful stools, a
      history of large fecal mass in rectum, and its disappearance of constipation
      symptoms after passing a large stool. Our study found different approaches
      amongst pediatric gastroenterologists like rectal examinations, disimpaction, or
      drug treatment. Several factors addressed in our study can provide better
      guidelines for clinicians treating constipation and its future research. 

PMID- 24015044
TI  - Early experience of pre- and post-contrast 7.0T MRI in brain tumors.
AB  - We investigated the safety and clinical applicability of 7.0 Tesla (T) brain
      magnetic resonance imaging (MRI) in patients with brain tumors. Twenty-four
      patients with intraaxial or extraaxial brain tumors were enrolled in this study.
      7.0T MRIs of T2*-weighted axial and T1-weighted coronal or sagittal images were
      obtained and compared with 1.5T brain MRIs. The T2*-weighted images from 7.0T
      brain MRI revealed detailed microvasculature and the internal contents of
      supratentorial brain tumors better than that of 1.5T brain MRI. For brain tumors
      located in parasellar areas or areas adjacent to major cerebral vessels, flow
      related artifacts were exaggerated in the 7.0T brain MRIs. For brain tumors
      adjacent to the skull base, susceptibility artifacts in the interfacing areas of
      the paranasal sinus and skull base hampered the aquisition of detailed images and
      information on brain tumors in the 7.0T brain MRIs. This study shows that 7.0T
      brain MRI can provide detailed information on the intratumoral components and
      margins in supratentorial brain tumors. Further studies are needed to develop
      refined MRI protocols for better images of brain tumors located in the skull
      base, parasellar, and adjacent major cerebrovascular structures. 

PMID- 24015045
TI  - Prevalence of snoring and high risk of obstructive sleep apnea syndrome in young
      male soldiers in Korea.
AB  - There are little information on prevalence of obstructive sleep apnea syndrome
      (OSAS) and clinical features in the young military population. The purpose of
      this study was to estimate the prevalence of snoring and high risk of OSAS in
      young male soldiers in Korea and to identify the risk factors of OSAS. A total of
      665 participants (aged 20-23 yr) who visited the Armed Forces Ildong Hospital for
      regular physical examination were enrolled. All participants completed the Berlin
      Questionnaire and underwent a physical examination. The participants with high
      risk for OSAS completed portable sleep monitoring. The prevalence of snoring and
      high risk of OSAS in young male soldiers in Korea was 13.5% and 8.1%,
      respectively. The prevalence of high arched palate, tongue indentation, long
      uvula, large tonsil and retrognathia was significantly higher in the high risk
      OSAS group. High arched palate, long uvula or low lying soft palate, tonsil size
      III or IV, Epworth Sleepiness Scale score > 10 and obesity (BMI > 27 kg/m(2))
      were found to independently predict OSAS. For early identification and treatment
      of young soldiers with OSAS in a military environment, a precise screening by
      questionnaire and physical examination is needed. 

PMID- 24015046
TI  - Poor prognosis in elderly patients who refused surgery because of economic burden
      and medical problem after hip fracture.
AB  - Although many studies have assessed mortality and morbidity of conservative
      treatment after hip fracture in elderly patients, the mortality of conservative
      treatment done because of economic burden is unclear. Among 451 patients
      diagnosed with displaced hip fracture during 3 yr, 28 patients (Group I) were
      enrolled as conservative treatment. Fifty-six patients matched in age, gender,
      ASA score, and diagnosis (Group II) who had undergone surgical treatment were
      used as the control group. The causal factors of non-operative treatment and
      mortality rate and functional recovery were evaluated according to the causal
      factors of patients with surgical procedure. Ten patients (36%) in Group I
      involved medical problems and 18 (64%) by economic burdens. The cumulative
      mortality rate over 3, 6, 12, and 24 months was 54%, 61%, 64%, and 82% in Group I
      and 9%, 11%, 14%, and 21% in Group II, respectively. At the latest follow-up, all
      five patients in Group I displayed a nonfunctional ambulatory state, whereas only
      seven of 44 patients in Group II were in a nonfunctional ambulatory state. Non
      surgical treatment following hip fracture that is done because of the economic
      burden is associated with substantially high mortality and serious functional
      loss. 

PMID- 24015047
TI  - Incidence of deep vein thrombosis after spinal cord injury in Korean patients at
      acute rehabilitation unit.
AB  - Deep vein thrombosis (DVT) and subsequent pulmonary embolism (PE) remain
      significant causes of morbidity, mortality in patients with spinal cord injury
      (SCI). Since incidence of DVT after SCI in Korean population has not been much
      studied, we retrospectively analyzed the medical records of 185 SCI patients
      admitted for acute rehabilitation unit to investigate the incidence of DVT. Color
      Doppler ultrasonography was performed to screen for the occurrence of DVT at the
      time of initial presentation to acute rehabilitation unit. Primary study outcome
      was the incidence of DVT. Possible risk factors for DVT including the
      epidemiologic characteristics, completeness of motor paralysis, cause of injury,
      spasticity, surgery, and active cancer were analyzed. The incidence of DVT after
      SCI was 27.6%. In multiple logistic regression analysis, absence of spasticity
      was a significant independent risk factor (P<0.05) for occurrence of DVT.
      Symptomatic pulmonary embolism was evident in 7 patients without an episode of
      sudden death. Therefore, it is concluded that the incidence of DVT after SCI in
      Korean patients is comparable with that in Western populations. This result
      suggests that pharmacologic thromboprophylaxis should be considered in Korean
      patients with SCI. 

PMID- 24015048
TI  - Single nucleotide deletion mutation of KCNH2 gene is responsible for LQT syndrome
      in a 3-generation Korean family.
AB  - Long QT syndrome (LQTS) is characterized by the prolongation of the QT interval
      in ECG and manifests predisposition to life threatening arrhythmia which often
      leads to sudden cardiac death. We encountered a 3-generation family with 5
      affected family members in which LQTS was inherited in autosomal dominant manner.
      The LQTS is considered an ion channel disorder in which the type and location of
      the genetic mutation determines to a large extent the expression of the clinical
      syndrome. Upon screening of the genomic sequences of cardiac potassium ion
      channel genes, we found a single nucleotide C deletion mutation in the exon 3 of
      KCNH2 gene that co-segregates with the LQTS in this family. This mutation
      presumably resulted in a frameshift mutation, P151fs+15X. This study added a new
      genetic cause to the pool of mutations that lead to defected potassium ion
      channels in the heart. 

PMID- 24015049
TI  - An infant with prenatally diagnosed congenital anaplastic astrocytoma who remains
      disease-free after proton therapy.
AB  - The authors present a rare of prenatally diagnosed congenital anaplastic
      astrocytoma. A 9-month-old boy had three recurrences despite two surgical
      resections and various chemotherapeutic regimens. He underwent the 3rd gross
      tumor removal at 11 months of age, followed by proton therapy, and now he remains
      disease-free for 3 yr without a significant neurocognitive dysfunction. This is
      the 1st case of a pediatric tumor treated by proton therapy in Korea, and proton
      therapy may be a treatment of choice for a congenital anaplastic astrocytoma in
      infants and young children, considering limitation of radiation therapy. 

PMID- 24015050
TI  - Muscular sarcoidosis detected by F-18 FDG PET/CT in a hypercalcemic patient.
AB  - Sarcoidosis is a systemic granulomatous disease of unknown etiology that involves
      many organs, occasionally mimicking malignancy. We herein report a 50-yr-old
      woman of muscular sarcoidosis of chronic myopathic type, manifested by
      hypercalcemia and muscle wasting. Besides insignificant hilar lymphadenopathy,
      her sarcoidosis was confined to generalized atrophic muscles and therefore, F-18
      FDG PET/CT alone among conventional imaging studies provided diagnostic clues for
      the non-parathyroid-related hypercalcemia. On follow-up PET/CT during low-dose
      steroid treatment, FDG uptake in the muscles disappeared whereas that in the
      hilar lymph nodes remained. PET/CT may be useful in the evaluation of unexpected
      disease extent and monitoring treatment response in suspected or known
      sarcoidosis patients. 

PMID- 24015051
TI  - Association of the catechol-o-methyltransferase gene polymorphisms with Korean
      autism spectrum disorders.
AB  - This study evaluated the family-based genetic association between autism spectrum
      disorders (ASDs) and 5 single-nucleotide polymorphisms (SNPs) in the catechol-o
      methyltransferase gene (COMT), which was found among 151 Korean ASDs family trios
      (dominant model Z = 2.598, P = 0.009, P FDR = 0.045). We found a statistically
      significant allele transmission or association in terms of the rs6269 SNP in the
      ASDs trios. Moreover, in the haplotype analysis, the haplotypes with rs6269
      demonstrated significant evidence of an association with ASDs (additive model
      rs6269-rs4818-rs4680-rs769224 haplotype P = 0.004, P FDR = 0.040). Thus, an
      association may exist between the variants of the COMT gene and the occurrence of
      ASDs in Koreans. 

PMID- 24015052
TI  - National trends of surgical treatment for intertrochanteric fractures in Korea.
AB  - Intramedullary nailing has been reported to have better outcome compared with
      traditional plate fixation in surgical treatment of intertrochanteric fractures.
      We evaluated the trends of surgical treatment of intertrochanteric fracture in
      Korea. Data of patients with intertrochanteric fractures, who were operated
      between the years of 2006 and 2011, was obtained from the Health Insurance Review
      and Assessment Service. The ratio of intramedullary nailing increased from 27.9%
      in 2006 to 64.3% in 2011 (P < 0.001), while the ratio of plate fixation
      decreased. During recent 5 yr, the utilization of intramedullary nailing doubled
      in clinical practice of intertrochanteric fractures in Korea. 

PMID- 24015053
TI  - Bed sharing deaths in infancy - sids or asphyxia?

PMID- 24015054
TI  - Resolution of UTIs post deflux injections for VUR may be due to the cure of BBD.

PMID- 24015056
TI  - Immediate Effects of a School Readiness Intervention for Children in Foster Care.
AB  - RESEARCH FINDINGS: School readiness is a strong predictor of adjustment in
      elementary school and beyond. Children in foster care are at particular risk for
      academic and social difficulties in school. Limitations in self-regulatory skills
      and caregiver involvement among these children might contribute to a lack of
      school readiness. This study presents the immediate effects on school readiness
      of a targeted, short-term intervention designed to improve children's early
      literacy, prosocial, and self-regulatory skills during the summer before
      kindergarten entry: Kids in Transition to School (KITS). Using a randomized
      controlled trial design, 192 children in foster care were assigned to either an
      intervention or services as usual comparison condition. Multimethod, multiagent
      assessments were conducted immediately prior to and following the completion of
      the intervention. The results from structural equation modeling indicated that
      the intervention had significant, positive effects on early literacy and self
      regulatory skills. PRACTICE: An efficacious, short-term, readily scalable,
      theoretically-based intervention targeted at specific vulnerabilities for
      children in foster care may help to improve their school readiness and eventual
      school adjustment.

PMID- 24015057
TI  - Exploring Parental Predictors of Child Anxiety: The Mediating Role of Child
      Interpretation Bias.
AB  - BACKGROUND: Separate lines of research have shown that higher levels of parental
      overcontrol and parental anxiety are related to higher levels of child anxiety.
      The mechanisms of transmission, however, are poorly understood. OBJECTIVE: It has
      been theorized, though not empirically tested, that parental overcontrol and
      anxiety increase children's interpretation bias by signaling to the child that
      the environment is threatening (e.g. through modeling or restriction of
      autonomy), thus increasing the child's anxiety level. METHODS: The present study
      investigated this theory using 75 parent-child dyads (parents aged 27-52, 82 %
      female; children aged 7-12, 52 % female, 80 % Caucasian). All parents were
      diagnosed with a primary anxiety disorder, while no child was diagnosed with an
      anxiety disorder. RESULTS: Children's interpretation bias, measured using
      ambiguous stories, was shown to partially mediate the relation between parental
      overcontrol and child anxiety and completely mediate the relation between
      parental anxiety and child anxiety. There was no significant relation between
      parental overcontrol and parental anxiety. CONCLUSIONS: Findings partially
      support theoretical models, which posit that higher levels of overcontrol and
      parental anxiety signal to children that their environment is threatening,
      perhaps increasing their threat appraisal of ambiguous situations and increasing
      their anxiety. Implications and directions for future research are discussed.

PMID- 24015058
TI  - COPD exacerbations admitted to intensive care unit. Organization, mortality, and
      noninvasive or invasive mechanical ventilation strategies: are they sufficiently
      well known?

PMID- 24015059
TI  - Notes on three species of the genus euphoriomyces (laboulbeniales) from Korea.
AB  - Three species of the genus Euphoriomyces (Laboulbeniales) were found newly from
      Korea. E. agathidii (Maire) Tavales was collected from Agathidium sp. (Leiodidae,
      Coleoptera). The characteristic traits of this species are the distal portion of
      the primary axis composed of 5~11 superposed layers and bearing more or less the
      elongated appendages. E. cybocephali (Thaxter) Thaxter was collected from
      Pseudocolenis hilleri Reitter (Leiodidae, Coleoptera). The primary axis of this
      species composed of 5~9 superposed layers is simple, not branched and a single
      antheridium occurs on the apex of the secondary axis. E. sugiyamae Majewski was
      collected from Scaphisoma rufum Achard (Scaphidiidae, Coleoptera). This species
      is very unique in having the antheridia formed as coner cells with lateral necks.

PMID- 24015060
TI  - Effect of Various Sawdusts and Logs Media on the Fruiting Body Formation of
      Phellinus gilvus.
AB  - Present experiments were conducted to determine the possibility of artificial
      culture with various sawdust of P. gilvus. The pH value was 6.0 of oak sawdust,
      6.5 of mulberry sawdust, 6.6 of elm sawdust, 6.3 of acacia sawdust and 6.1 of
      apple tree sawdust. Mycelial density on elm sawdust and acacia sawdust were lower
      than those of oak sawdust, and apple sawdust. Weight of fresh fruiting body
      showed that 179 g on oak tree, 227 g on oak sawdust, 21 g on elm tree, 76 g on
      elm sawdust, 106 g on apple tree, and 170 g on apple sawdust. Among them, the
      yield of oak substrates was the highest whereas acacia sawdust was the lowest,
      and it is concluded that the yields of sawdust substrates were higher than log
      substrates. P. gilvus grown on various sawdusts and logs used in this study have
      shown similar in anti-tumor activity against P388. 

PMID- 24015061
TI  - The Neuroprotective and Neurotrophic Effects of Tremella fuciformis in PC12h
      Cells.
AB  - We examined the neuroprotective and neurotrophic effects of Tremella fuciformis.
      The neurotrophic effects of the hot water extract of T. fuciformis was evaluated
      by microscopically monitoring its potency to induce neurite outgrowth in PC12h
      cells. The hot water extract of T. fuciformis promoted neurite outgrowth in PC12h
      cells in this study, superior to other natural substances which was reported
      previously. When cells were treated with the hot water extract of T. fuciformis
      prior to beta-amyloid peptide treatment (active domain of A peptide 25~35
      treated), toxicity was significantly diminished (p<0.01). These results suggest
      that T. fuciformis might potentially be used as a precautionary agent in
      neurodegenerative disease, such as Alzheimer's disease, etc. 

PMID- 24015062
TI  - Hypolipidemic Effects of Biopolymers Extracted from Culture Broth, Mycelia, and
      Fruiting Bodies of Auricularia auricula-judae in Dietary-induced Hyperlipidemic
      Rats.
AB  - Hypolipidemic effect of biopolymers extracted from culture broth (CP), mycelia
      (MP), and fruiting bodies (FP) of Auricularia auricula-judae was investigated in
      dietary-induced hyperlipidemic rats. The experimental animals were administrated
      (100 mg/kg body weight) with different biopolymers, daily for 4 weeks.
      Hypolipidemic effects were achieved in all the experimental groups, however, FP
      was proved to be the most potent one. The administration of the FP reduced the
      plasma triglyceride, total cholesterol, low-density lipoprotein cholesterol, and
      atherogenic index by 24.3, 28.5, 36.4, and 40.9%, respectively, while increased
      the high-density lipoprotein cholesterol level (9.0%), when compared to the
      saline (control) administered group. 

PMID- 24015063
TI  - Comparison of dyes for easy detection of extracellular cellulases in fungi.
AB  - To evaluate which dye is effective in a plate assay for detecting extracellular
      cellulase activity produced by fungi, four chromogenic dyes including remazol
      brilliant blue, phenol red, congo red, and tryphan blue, were compared using
      chromagenic media. For the comparison, 19 fungal species belonging to three
      phyla, ascomycota, basidiomycota, and zygomycota were inoculated onto yeast
      nitrogen-based media containing different carbon substrates such as cellulose
      (carboxylmethyl and avicel types) and cellobiose labeled with each of the four
      dyes. Overall, the formation of clear zone on agar media resulting from the
      degradation of the substrates by the enzymes secreted from the test fungi was
      most apparent with media containing congo red. The detection frequency of
      cellulase activity was also most high on congo red-supplemented media. The
      results of this study showed that congo red is better dye than other three dyes
      in a plate assay for fungal enzyme detection. 

PMID- 24015064
TI  - Biological Screening of a Novel Nickel (II) Tyrosine Complex.
AB  - A newly synthesized Nickel (II) tyrosine complex was screened as potential
      antimicrobial agent against a number of medically important bacteria (Bacillus
      subtilis, Streptococcus beta-haemolytica, Escherichia coli, Shigella dysenterae)
      and fungi (Aspergillus fumigatus, Candida albicans, Aspergillus niger,
      Aspergillus flavus, Penicillium sp.) strains. were used for antifungal activity.
      The antimicrobial activity was evaluated using the Agar Disc method. Moreover,
      the minimum inhibitory concentration of the complexes was determined against the
      same pathogenic bacteria and the values were found between 4~64 ug ml (-1). Brine
      shrimp bioassay was carried out for cytotoxicity measurements of the complexes.
      The LC50 values were calculated after probit transformation of the resulting
      mortality data and found to be 6 ug ml (-1). 

PMID- 24015065
TI  - Characterization of a brown rot fungus isolated from dwarf flowering almond in
      Korea.
AB  - The fruits showing brown rot symptom on dwarf flowering almond were found in
      Gongju, Chungchungnam-Do in Korea in July 2005. Small water-soaked lesions on the
      fruits were initiated, and gradually developed to soft rot covered with gray
      conidia. Then the diseased fruits were shrunk and became grayish-black mummies. A
      fungus was isolated from the diseased fruit and its morphological, cultural and
      molecular genetic characteristics were investigated. Typical blastospores of
      Monilinia spp. were observed under a light microscope both from tissues of the
      diseased fruits and from PDA-grown cultures. The fungus grew well at 25C and on
      PDA. The ITS ribosomal DNA region (650 bp) of the fungus was amplified by PCR and
      analyzed. Comparative data on ITS sequence homology among Monilinia spp., ITS
      sequence-based phylogram and morphological characteristics showed that the fungus
      is Monilinia fructicola. This is the first report on Monilinia fructicola causing
      brown rot on fruits of dwarf flowering almond in Korea. 

PMID- 24015066
TI  - Populations of fungi and bacteria associated with samples of stored rice in
      Korea.
AB  - Stored rice was collected from rice processing complexes of National Agricultural
      Cooperative Federation of 11 regions in Korea to evaluate the occurrence of fungi
      and bacteria and to identify the predominant fungi and bacteria to the genus
      levels. Most rice samples generally produced the higher levels of fungi and
      bacteria than white rice. The occurrence of fungi and bacteria varied in various
      locations of Korea. Among fungi observed, Aspergillus spp. and Penicillium spp.
      were dominant in the samples and Aspergillus spp. were observed more frequently
      than Penicillium spp. Predominant bacteria from rice and white rice samples
      tentatively belonged to the Genus Bacillus, Pectobacterium, Pantoea, and
      Microbacterium according to BIOLOG and FAME analyses. The results of this study
      showed that rice in Korea was contaminated in a relatively high level by two
      dominant storage fungi such as Aspergillus spp. and Penicillium spp. In addition,
      occurrence of mycotoxins in rice by the fungi could be possible and thus it is
      necessary to control the storage fungi. 

PMID- 24015067
TI  - Furfural from Pine Needle Extract Inhibits the Growth of a Plant Pathogenic
      Fungus, Alternaria mali.
AB  - The antifungal effect of pine needle extract prepared by a distinguishable
      extraction method and the dry distillation method, was examined. The effect of
      this extract itself was insignificant. The chemical components of pine needle
      extract were then investigated by gas chromatographic analysis, and four chemical
      components, acetol, furfural, 5-methyl furfural, and terpine-4-ol, were
      identified. The antifungal effects of those four chemical components against
      Alternaria mali (A. mali), an agent of Alternaria blotch of apple, were then
      examined. It was observed that the minimum inhibitory concentrations (MICs) were
      6.25, 0.78, 0.78, and 12.5 (mg/ml) of acetol, furfural, 5-methyl furfural, and
      terpine-4-ol, respectively. MICs of furfural and 5-methyl furfural had the same
      order of magnitude as that of an antifungal agrochemical, chlorothalonil.
      Although furfural itself can not be completely substituted for an antifungal
      agrochemical, a partial mixture of furfural and antifungal agrochemical may be
      used as a substitute. The use of agrochemicals for the prevention of plant
      disease caused by pathogenic fungus such as A. mali could be partially reduced by
      the application of this mixture. 

PMID- 24015068
TI  - New Record of Lecanora muralis (Lichenized Fungus) in South Korea.
AB  - Lecanora muralis was found on the rock along coastal line during the field trip
      in Jeju island in 2006. Thallus crustose, placodioid, closely adnate, forming
      orbicular patches; upper surface grayish green, glossy; central lobes areolate,
      marginal parts plane, edges thin pruinose; lower surface ecorticate; apothecia
      sessile, lecanorine type, exciple dense and intact when young, and disc plane,
      but when mature, exciple laciniate, disc protrudent, yellowish brown to orange,
      0.5~1.5 mm in diameter; ascospores ellipsoid, simple, colorless, 12.5~15.0 *
      5.0~7.5 um. Usnic acid and zeorin contained in thallus. This is the first record
      of this species in South Korea. 

PMID- 24015069
TI  - Spices mycobiota and mycotoxins available in saudi arabia and their abilities to
      inhibit growth of some toxigenic fungi.
AB  - The prevalence and population density of the mycobiota of 50 samples belonging to
      10 kinds of spices (anise, black pepper, red pepper, black cumin, peppermint,
      cardamom, clove, cumin, ginger and marjoram) which collected from different
      places in Jeddah Governorate were studied. The natural occurrence of mycotoxins
      in those samples was also investigated. Fifteen genera and thirty - one species
      of fungi in addition to one species variety were isolated and identified during
      this study. The most common genera were Aspergillus, Penicillium and Fusarium.
      Aflatoxins (12~40 ug/kg) were detected in the extract of 5 samples of each of
      anise seeds and black pepper fruits; three samples of black cumin seeds and on
      sample only of each of peppermint and marjoram leaves out of 5 samples tested of
      each. Sterigmatocystin (15~20 ug/kg) was detected in some samples of red pepper,
      cumin and marjoram. The inhibitory effects of 10 kinds of powdered spices were
      tested against 3 toxigenic isolates of fungi (Aspergillus flavus, A. versicolor
      and Penicillium citrinum). Clove proved to be antimycotic compounds. It inhibited
      the growth of the tested toxigenic fungi. Black pepper, peppermint, cardamom,
      cumin and marjoram completely inhibited aflatoxins production, while black pepper
      and cardamom also completely inhibited sterigmatocystin production. 

PMID- 24015070
TI  - Proliferation of Tricholoma matsutake Mycelial Mats in Pine Forest Using Mass
      Liquid Inoculum.
AB  - Two isolates of Tricholoma matsutake T-008 and T-034, preserved in
      Entomopathogenic Fungal Culture Collection (EFCC) of Korea, were used in the
      present study. The isolates had 100% Bootstrap homology with Tricholoma matsutake
      U62964 and T. matsutake AB188557 and AF309538 preserved in Gene Bank of NCBI.
      Mycelial growth of T. matsutake was highest in TMM and MYA at 25C. The highest
      dry wt. of mycelium was obtained after 65 days of culture, when 6 mycelial discs
      were inoculated in 100 ml of broth in 250 ml shaking flask. Mycelial mats were
      observed in clumped condition at the inoculation sites of pine forest after two
      weeks of inoculation. After 5 months of inoculation, mycelia mats were observed
      growing inside soil and walls of a few inoculation sites, while mycelial mats
      growth up to 5~8 cm were observed in the roots of pine tree after 6 months. The
      survival rate of the inoculum was about 40% of the total inoculation sites. The
      survival rate was found below 20% when the mycelium was inoculated in the summer.
      The reasons for low survival rates of the mycelium were mainly due to dry season
      and the soil-borne small animals such as earthworm and mole. After one year of
      inoculation, no external difference was observed between the artificially
      inoculated mycelia and the naturally existing mycelia of T. matsutake. The
      present study showed that fruiting bodies of T. matsutake could be produced by
      artificial inoculation under the appropriate environmental conditions. 

PMID- 24015071
TI  - Antifungal Activity of an Alkaloid Allosecurinine against Some Fungi.
AB  - An allosecurinine alkaloid was assayed against spore germination of some
      saprophytic and pathogenic fungi e.g., Alternaria alternata, A. solani, A.
      brassicicola, A. brassicae, Curvularia lunata, C. pallescens, C. maculans,
      Curvularia species, Colletotrichum species, C. musae, C. gloeosporioides,
      Erysiphe pisi, Fusarium udum, Helminthosporium echinoclova, H. pennisetti, H.
      spiciferum, and Heterosporium sp. It inhibited mild spore germination of all the
      fungi tested. Curvularia lunata, Curvularia sp., Collectotrichum sp., C. musae
      and Heterosporium sp. were most sensitive as complete inhibition of spore
      germination was observed at very low concentrations. 

PMID- 24015072
TI  - Designing and synthesis of antifungal active macrocyclic ligand and its complexes
      derived from diethylphthalate and benzidine.
AB  - Three novel complexes of Cu(II), Co(II) and Zn(II) using a macrocyclic ligand
      derived by the condensation of diethylphthalate and benzidine have been
      designed,synthesized and characterized by UV-Vis.,IR,Mass and Elemental analyses
      data in order to find out their antifungal activities. The stoichiometry of the
      complexes has been found to be 1: 1(Metal : Ligand). The analytical data indicate
      that the complexes exhibit square-planar geometry. The antifungal activity of the
      macrocyclic ligand and its metal complexes has been screened in vitro against
      fungi such as Aspergillus niger, A. flavus, Trichoderma harizanum, T. viridae and
      Rhizoctonia solani. 

PMID- 24015073
TI  - Effect of 1-corydalmine,an Alkaloid Isolated from Corydalis chaerophylla Roots on
      Spore Germination of Some Fungi.
AB  - 1-Corydalmine,an alkaloid isolated from roots of Corydalis chaerophylla inhibited
      spore germination of some plant pathogenic as well as saprophytic fungi e.g.
      Alternaria brassicae, A. brassicicola, A. solani, Curvularia lunata, C. maculans,
      C. sp., C. pallscens, Erysiphe pisi, Fusarium udum, Helminthosporium species,H.
      penniseti and a Heterosporium species. 1-Corydalmine significantly inhibited
      spore germination of all the fungi at 100 to 1500 ppm. It was effective against
      all the fungi at 1500 ppm. C. lunata was highly sensitive to this chemical even
      at 250 ppm. 

PMID- 24015074
TI  - Antifungal activity of 2-hydroxy 4,4'6'trimethoxy chalcone.
AB  - Antifungal activity of 2-hydroxy 4,4'6'trimethoxy chalcone individually was
      tested against spore germination of ten fungi of different genera. Efficacy of
      the chemical was also tested against conidial germination and other growth
      parameters of Erysiphe pisi on excised pea leaves. 2-Hydroxy 4,4'6'trimethoxy
      chalcone inhibited spore germination at all the concentrations. Maximum
      inhibition was observed at 2000 ppm where more than 78 per cent inhibition of
      spore germination was observed in Ustilago cynodontis, Alternaria brassicicola,
      A. solani and Aspergillus flavus. It also reduced conidial germination of E. pisi
      significantly, when applied as pre-inoculation treatment. 

PMID- 24015075
TI  - Inhibition of Aflatoxin Production of Aspergillus flavus by Lactobacillus casei.
AB  - Lactobacillus casei KC-324 was tested for its ability to inhibit aflatoxin
      production and mycelial growth of Aspergillus flavus ATCC 15517 in liquid
      culture. Aflatoxin B1 biosynthesis and mycelial growth were inhibited in both
      simultaneous culture and individual antagonism assays,suggesting that the
      inhibitory activity was due to extracellular metabolites produced in cell-free
      supernatant fluids of the cultured broth of L. casei KC-324. In cell-free
      supernatant fluids of all media tested,deMan,Rogosa and Sharpe broth,potato
      dextrose broth,and Czapek-Dox broth + 1% yeast extract showed higher
      antiaflatoxigenic activity. In these case, fungal growths, however, was not
      affected as measured by mycelial dry weight. The antiaflatoxigenic metabolites
      from L. casei KC-324 were produced over wide range of temperatures between 25C
      and 37C. However, these metabolites were not thermostable since the inhibitory
      activity of the supernatant was inactivated within 30 minutes at 100C and 121C.
      The inhibitory activity was not influenced by changing pH of supernatant between
      4 and 10. However,the antiaflatoxigenic activity was slightly reduced at pH 10. 

PMID- 24015076
TI  - Improvement of Ergone Production from Mycelial Culture of Polyporus umbellatus.
AB  - Ergone,a fungal metabolite derived from ergosterol,was previously isolated and
      identified from Polyporus umbellatus. Ergone is a major component of P.
      umbellatus known to have anti-aldosteronic diuretic effect and also displays
      cytotoxic activities. Most of mushroom's fruit bodies used for test contained
      less than 10 ug/g of ergone. But P. umbellatus have larger amount of ergone than
      any other mushrooms. In order to improve the ergone production from the submerged
      culture of P. umbellatus, several factors including medium composition,culture
      conditions (temperature and pH) and different combinations of co-cultivation with
      various mycelia were studied. Among various carbon sources examined,starch proved
      to be most effective for the production of mycelia. The optimum pH and
      temperature for a flask culture of P. umbellatus mycelia were found to be 4.5 and
      25C,respectively. Under the optimized culture conditions,both the ergone
      production (86.9 ug/g) and mycelial growth (3.5 g/l) increased when P. umbellatus
      was cultured with Armillariella mellea. When the optimized conditions were
      applied,both mycelium and ergone production were significantly enhanced. 

PMID- 24015077
TI  - Identification and distribution of two fungal species causing sclerotial disease
      on mulberry fruits in Korea.
AB  - A total of 520 overwintered sclerotia were collected from surface of soil under
      mulberry trees in six locations in Korea during February in 2006 and 2007. The
      collected sclerotia were tested for their germination in vitro and identified
      based on their morphological characteristics. Out of all sclerotia tested, 52.3%
      of the sclerotia germinated and produced two types of apothecia. The two types of
      fungi occurred from the sclerotia at the ratio of 49.8 vs. 50.2. The fungal type
      with cup-shaped apothecia was identified as Ciboria shiraiana and another type of
      fungus with club-shaped apothecia as Scleromitrula shiraiana. Taxonomy and
      distribution of the two sclerotial fungi were described and discussed. 

PMID- 24015078
TI  - Characterization of Fusarium oxysporum Isolated from Paprika in Korea.
AB  - In the present study we first report in Korea the identification and
      characterization of Fusarium oxysporum isolated from rotten stems and roots of
      paprika (Capsicum annuum var. grossum) at Masan, Kyungsangnamdo in 2006. The
      fungal species produced white aerial mycelia accompanying with dark violet
      pigment on PDA. The optimal temperature and pH for the growth of the species was
      25C and pH 7, respectively. Microscopic observation of one of isolates of the
      species shows that its conidiophores are unbranched and monophialides, its
      microconidia have oval-ellipsoidal shape with no septate and are of 3.0~11 *
      1.5~3.5 um sizes, its macroconidia are of 15~20 * 2.0~3.5 um sizes and have
      slightly curved or slender shape with 2~3 septate. The results of molecular
      analysis show that the ITS rDNA of F. oxysporum from paprika shares 100% sequence
      identity with that of known F. oxysporum isolates. The identified species proved
      it's pathogenicity by causing rotting symptom when it was inoculated on paprika
      fruits. The growth of F. oxysporum from paprika was suppressed on PDA by
      agrochemicals such as benomyl, tebuconazole and azoxystrobin. The identified
      species has the ability of producing extracelluar enzymes that degrade cellobiose
      and pectin. 

PMID- 24015079
TI  - Two species of myxomycetes causing slime mold of sweet potato.
AB  - Specimens collected from sweet potato plants with slime mold symptoms in fields
      in Daejeon, Korea were examined. Two species of Myxomycetes, Fuligo septica and
      Stemonitis herbatica were identified based on their morphological
      characteristics. This is the first report that the two species of Myxomycetes
      cause slime mold of sweet potato in Korea. 

PMID- 24015080
TI  - Molds isolated from pet dogs.
AB  - Pet dogs have been considered to be involved in the contamination of indoor air
      by serving as a source of providing molds at houses. Currently, information on
      the molds originated from pet dogs is rarely available in Korea. The present
      study was carried out to obtain basic information on the fungi present on pet
      dogs. For this, fungal isolation was performed to the skin and hairs of 70 pet
      dogs at different houses and veterinary hospitals. A total of 44 fungal isolates
      were obtained from skin (27 isolates) and hairs (17 isolates) of the dogs
      investigated. Based on the observation of microstructures and colony morphology,
      and the ITS rDNA sequence analysis, the fungal isolates were identified at the
      level of genus. The identified isolates belong to the genera of Alternaria,
      Aspergillus, Beauveria, Chrysosporium, Cladosporium, Penicillium, Scopulariopsis,
      and Trichoderma. Among these genera, Aspergillus (25%), Cladosporium (23%) and
      Penicillium (20.5%) were 3 major genera. 63% of the 44 isolates showed color
      changes on dermatophyte test medium (DTM). When we tested the growth ability of
      44 isolates at 37C, 45% of the isolates were able to grow. These results show
      that pet dogs could carry fungi having a potentiality of affecting on human
      health. 

PMID- 24015081
TI  - Taxonomic study on the lichen genus cetrelia (lecanorales, ascomycota) in South
      Korea.
AB  - Seventy-two lichen specimens of Cetrelia collected in South Korea since 2003 were
      examined by both phenotypic and phylogenetic analyses. The phenotypic analysis
      was based on morphological and chemical characters, and the phylogenetic analysis
      was based on nrDNA ITS sequences. The result suggested that the presence and
      absence of isidia, soredia, lobules and medullar reaction C+ or C- are the
      important characters in the taxonomy of this genus. Four species of Cetrelia, C.
      chicitae, C. braunsiana, C. japonica, and C. pseudolivetorum have been identified
      in this study. Description of each species is presented with morphological and
      chemical characters. A key to the Cetrelia species is also presented. 

PMID- 24015082
TI  - Response of the Higher Basidiomycetic Ganoderma resinaceum to Sodium Chloride
      Stress.
AB  - Ganoderma resinaceum tolerated sodium chloride salt stress within a range of 0 mM
      till 300 mM. It responded to salt stress with fluctuation in proline formation at
      different NaCl concentrations. However,the mycelial dry weight,total protein
      contents and exopolysaccharides did not changed considerably. Increasing sodium
      chloride concentration led to morphological alteration in fungal mycelia with
      disappearance of fungal cell wall,plasmolysis,and vacuolation as indicated with
      electron microscopic examination of the fungal growth. 

PMID- 24015083
TI  - Foliar Application of Plant Growth-Promoting Rhizobacteria Increases Antifungal
      Compounds in Pea (Pisum sativum) Against Erysiphe pisi.
AB  - Systemic effect of two plant growth-promoting rhizobacterial (PGPR) strains,viz.,
      Pseudomonas fluorescens (Pf4) and P. aeruginosa (Pag), was evaluated on pea
      (Pisum sativum) against the powdery mildew pathogen Erysiphe pisi. Foliar spray
      of the two PGPR strains was done on specific nodal leaves of pea and conidial
      germination of E. pisi was observed on other nodal leaves,distal to the treated
      ones. Conidial germination was reduced on distant leaves and at the same
      time,specific as well as total phenolic compounds increased in the leaves distal
      to those applied with PGPR strains,thereby indicating a positive correlation. The
      strains induced accumulation of phenolic compounds in pea leaves and the amount
      increased when such leaves were get inoculated with E. pisi conidia. Between the
      two strains, Pag was found to be more effective than Pf4 as its effect was more
      persistent in pea leaves. Foliar application of PGPR strains for the control of
      powdery mildew of pea is demonstrated in vitro while correlating it with the
      increased accumulation of plant phenolics. 

PMID- 24015084
TI  - Removal Efficiency of the Heavy Metals Zn(II), Pb(II) and Cd(II) by Saprolegnia
      delica and Trichoderma viride at Different pH Values and Temperature Degrees.
AB  - The removal efficiency of the heavy metals Zn, Pb and Cd by the zoosporic fungal
      species Saprolegnia delica and the terrestrial fungus Trichoderma viride,
      isolated from polluted water drainages in the Delta of Nile in Egypt, as affected
      by various ranges of pH values and different temperature degrees,was extensively
      investigated. The maximum removal efficiency of S. delica for Zn(II) and Cd(II)
      was obtained at pH 8 and for Pb(II) was at pH 6 whilst the removal efficiency of
      T. viride was found to be optimum at pH 6 for the three applied heavy metals.
      Regardless the median lethal doses of the three heavy metals, Zn recorded the
      highest bioaccumulation potency by S. delica at all pH values except at pH 4,
      followed by Pb whereas Cd showed the lowest removal potency by the fungal species
      and vice versa in case of T. viride. The optimum biomass dry weight production by
      S. delica was found when the fungus was grown in the medium treated with the
      heavy metal Pb at pH 6, followed by Zn at pH 8 and Cd at pH 8. The optimum
      biomass dry weight yield by T. viride amended with Zn,Pb and Cd was obtained at
      pH 6 for the three heavy metals with the maximum value at Zn. The highest yield
      of biomass dry weight was found when T. viride treated with Cd at all different
      pH values followed by Pb whilst Zn output was the lowest and this result was
      reversed in case of S. delica. The maximum removal efficiency and the biomass dry
      weight production for the three tested heavy metals was obtained at the
      incubation temperature 20C in case of S. delica while it was 25C for T. viride.
      Incubation of T. viride at higher temperatures (30C and 35C) enhanced the removal
      efficiency of Pb and Cd than low temperatures (15C and 20C) and vice versa in
      case of Zn removal. At all tested incubation temperatures, the maximum yield of
      biomass dry weight was attained at Zn treatment by the two tested fungal species.
      The bioaccumulation potency of S. delica for Zn was higher than that for Pb at
      all temperature degrees of incubation and Cd bioaccumulation was the lowest
      whereas T. viride showed the highest removal efficiency for Pb followed by Cd and
      Zn was the minor of the heavy metals. 

PMID- 24015085
TI  - Anti-complementary Activities of Exo- and Endo-biopolymer Produced by Submerged
      Mycelial Culture of Eight Different Mushrooms.
AB  - The Elfvingia applanata (EA), Hericium erinaceum (HE),Grifola frondosa (GF),
      Pholiota nameko (PN), Pleurotus eryngii (PE), Trametes suaveolens (TS), Fomes
      fomentarius (FF), and Inonotus obliquus (IO) could produce the endo- (EN) and exo
      biopolymer (EX) in submerged culture. The highest anti-complementary activity of
      the EN was exhibited by PN (49.1%), followed by HE (38.6%), TS (37.0%),and FF
      (33.0%),whereas the high activity of the EX was found with GF (59.8%),followed by
      HE (36.3%),TS (30.8%),and IO (28.8%). The EN of P. nameko (EN-PN) and EX of G.
      frondosa (EX-GF) were found to contain 78.6% and 41.2% carbohydrates, while 21.4%
      and 58.8% protein, respectively. The sugar and amino acid compositions of EN-PN
      and EX-GF were also analyzed in detail. 

PMID- 24015086
TI  - Synthesis and spectral characterization of antifungal sensitive schiff base
      transition metal complexes.
AB  - New N2O2 donor type Schiff base has been designed and synthesized by condensing
      acetoacetanilido-4-aminoantipyrine with 2-aminobenzoic acid in ethanol. Solid
      metal complexes of the Schiff base with Cu(II), Ni(II), Co(II), Mn(II), Zn(II),
      VO(IV), Hg(II) and Cd(II) metal ions were synthesized and characterized by
      elemental analyses, magnetic susceptibility, molar conduction, fast atom
      bombardment (FAB) mass, IR, UV-Vis, and (1)H NMR spectral studies. The data show
      that the complexes have the composition of ML type. The UV-Vis. and magnetic
      susceptibility data of the complexes suggest a square-planar geometry around the
      central metal ion except VO(IV) complex which has square-pyramidal geometry. The
      in vitro antifungal activities of the compounds were tested against fungi such as
      Aspergillus niger, Aspergillus flavus, Rhizopus stolonifer, Candida albicans,
      Rhizoctonia bataicola and Trichoderma harizanum. All the metal complexes showed
      stronger antifungal activities than the free ligand. The minimum inhibitory
      concentrations (MIC) of the metal complexes were found in the range of 10~31
      ug/ml. 

PMID- 24015087
TI  - MushBase: A Mushroom Information Database Application.
AB  - A database application, namely MushBase, has been built based on Microsoft Access
      in order to store and manage different kinds of data about mushroom biological
      information of species, strains and their physiological characteristics such as
      geometries and growth condition(s). In addition, it is also designed to store
      another group of information that is experimental data about mushroom
      classification by Random Amplification of Polymorphic DNA (RAPD). These two
      groups of information are stored and managed in the way so that it is convenient
      to retrieve each group of data and to cross-refer between them as well. 

PMID- 24015088
TI  - Inhibitive Effect of Fuyuziphine isolated from Plant (Pittapapra) (Fumaria
      indica) on Spore Germination of Some Fungi.
AB  - The alkaloid fuyuziphine was isolated from the whole plant of Fumaria indica. It
      had inhibitive effect against spore germination of some plant pathogenic fungi
      (Collectotrichum sp., C. gloeosporioides, C. falcatum, Curvularia maculans, C.
      lunata, Erysiphe cichoracearum, Helminthosporium pennisetti, Oidium erysiphoides,
      Ustilago cynodontis, Alternaria chieranthi, A. melongenae, A. brassicicola and A.
      solani). Curvularia lunata, Oidium erysiphoides, Alternaria brassicicola and A.
      solani did not germinate at 750 and 1000 ppm and Colletotrichum gloeosporioides,
      C. falcatum, Curvularia maculans were inhibited at 1000 ppm for 24 hr incubation.
      Germination of most fungi was significantly inhibited at 100~750 ppm. 

PMID- 24015089
TI  - Fungi isolated from pine wood nematode, its vector Japanese pine sawyer, and the
      nematode-infected Japanese black pine wood in Korea.
AB  - Pine tree death caused by pine wood nematode (PWN) involves phoretic
      relationships between PWN and its vector Japanese pine sawyer beetle (JPS). In an
      effort to understand the diversity of fungi involved in PWN life cycle, a total
      of 176 fungal isolates were collected from PWNs, adults and larvae of JPS, PWN
      diseased Japanese black pine that was cut down in 2005 at Jinju, Korea. Based on
      microscopic observation and colony morphology, and sequence analysis of the ITS
      rDNA, the fungal isolates were identified at the level of genus. Three genera
      including Mucor, Ophiostoma, and Penicillium were identified from PWN. Two genera
      of Ophiostoma and Penicillium were discovered from JPS larvae. From JPS adult
      beetles, nine genera of Aspergillus, Gibberella, Hypocrea, Irpex, Leptosphaeria,
      Ophiostoma, Penicillium, and Plectosphaerella and unknown basidiomycetes were
      found. Ten genera from PWN-infected wood were confirmed as Bionectria, Botrytis,
      Camarops, Fusarium, Hypocrea, Nectrtia, Mucor, Ophiostoma, Penicillium, and
      Trichoderma. Penicillium and Ophiostoma were commonly distributed on PWN and its
      vector and host. This is first report of the fungi associated with PWN and its
      vector and host in Korea. 

PMID- 24015090
TI  - Detection of Extracellular enzymes Activities in Various Fusarium spp.
AB  - Thirty seven species of Fusarium were evaluated for their ability of producing
      extracellular enzymes using chromogenic medium containing substrates such as
      starch, cellobiose, CM-cellulose, xylan, and pectin. Among the tested species
      Fusarium mesoamericanum, F. graminearum, F. asiaticum, and F. acuminatum showed
      high beta-glucosidase acitivity. Xylanase activity was strongly detected in F.
      proliferatum and F. oxysporum. Strong pectinase activity was also found in F.
      oxysporum and F. proliferatum. Amylase activity was apparent in F. oxysporum. No
      clear activity in cellulase was found from all the Fusarium species tested. 

PMID- 24015091
TI  - Detection of Extracellular Enzyme Activity in Penicillium using Chromogenic
      Media.
AB  - A total of 106 Penicillium species were tested to examine their ability of
      degrading cellobiose, pectin and xylan. The activity of beta-glucosidase was
      generally strong in all the Penicillium species tested. P. citrinum, P.
      charlesii, P. manginii and P. aurantiacum showed the higher ability of producing
      beta-glucosidase than other tested species. Pectinase activity was detected in 24
      Penicillium species. P. paracanescens, P. sizovae, P. sartoryi, P. chrysogenum,
      and P. claviforme showed strong pectinase activity. In xylanase assay, 84
      Penicillium species showed activity. Strong xylanase activity was detected from
      P. megasporum, P. sartoryi, P. chrysogenum, P. glandicola, P. discolor, and P.
      coprophilum. Overall, most of the Penicillium species tested showed strong beta
      glucosidase activity. The degree of pectinase and xylanase activity varied
      depending on Penicillium species. 

PMID- 24015092
TI  - New Record of Xylaria persicaria on Liquidambar Fruits in Korea.
AB  - Some Xylaria materials growing on the fruits of Liquidambar spp. were collected.
      They were identified as X. persicaria on the basis of morphological
      characteristics and sequence analysis of the complete ITS region (ITS1-5.8S-ITS2)
      of rDNA. This is the first record of this species from Korea. 

PMID- 24015093
TI  - Taxonomic study on the lichen genus coccocarpia (lecanorales, ascomycota) in
      South Korea.
AB  - Three species of Coccocarpia have been reported from Korean Peninsular. However,
      there was no revisional study on this genus before. After careful examination of
      the specimens deposited in the Korean Lichen Research Institute (KoLRI) and
      collected from main mountain areas of Korea, two species of Coccocarpia, C.
      palmicola and C. erythroxyli, have been revealed to occur and confirmed in South
      Korea. The presence and absence of isidia and apothecia are the most important
      characters for the South Korean species. We provide the detailed description and
      illustration of the available two species. A key to the species is also provided.

PMID- 24015094
TI  - Six species of penicillium associated with blue mold of grape.
AB  - Grape fruits with blue mold symptoms were collected from house storages in
      different locations in Korea and were investigated for their association with
      Penicillium species. A total of 12 isolates of Penicillium were isolated from the
      collected fruits. Based on morphological and cultural characteristics and beta
      tublin gene sequence data analysis, they were identified as P. bialowiezense, P.
      citrinum, P. echinulatum, P. expansum, P. solitum and unidentified Penicillium
      species. P. solitum was the predominant followed by P. expansum. P. bialowiezense
      and P. echinulatum were newly recorded in Korea. beta-Tubulin gene sequences
      could be used to distinguish each species of Penicillium and the molecular groups
      were correlated well with the morphological species. The unidentified species was
      supposed to be a new species, not previously reported in literature. 

PMID- 24015095
TI  - Effects of mycorrhizal and endophytic fungi on plant community: a microcosm
      study.
AB  - This study was conducted to investigate the effects of foliar endophytic fungi
      and arbuscular mycorrhizal fungi (AMF) on plant community structure in
      experimental microcosms containing an assemblage of five species of plants
      (Oenothera odorata, Plantago asiatica, Trifolium repens, Isodon japonicas and
      Aster yomena). Leaves of Sasa borealis, Potentilla fragarioides, and Viola
      mandshurica were collected in Chungbuk, Korea. Endophytic fungi were isolated
      from the surface sterilized leaves and identified to species level using
      molecular and morphological techniques. Four isolates of the endophytic fungi
      were inoculated to the leaves of host plants in the microcosms. Also, three
      species of AMF spores were extracted from pure cultures and the mixture of the
      three species inoculated to the roots of the plants. After four months of growth
      in a green house, effects of both symbiotic fungi on plant species diversity,
      community composition and productivity were examined. The plant species diversity
      showed significant differences with inoculation of the symbiotic fungi. Results
      indicate that AMF significantly affect plant productivity and plant community
      structure. 

PMID- 24015096
TI  - Variation of Soil Mycoflora in Decomposition of Rice Stubble from Rice-wheat
      Cropping System.
AB  - The colonization pattern and extent of decay produced in paddy stubble by soil
      inhabiting mycoflora were done by using nylon net bag technique. Among the three
      methods used for isolation of fungi, dilution plate technique recorded the
      highest number of fungi followed by damp chamber and direct observation method.
      Nutrient availability and climatic conditions (temperature, humidity and
      rainfall) influenced the occurrence and colonization pattern of fungi. Maximum
      fungal population was recorded in October (48.99 * 10(4)/g dry litter) and
      minimum in May (11.41 * 10(4)/g dry litter). Distribution of Deuteromycetous
      fungi was more in comparison to Zygomycetes, oomycetes and ascomycetes. In the
      early stage of decomposition Mucor racemosus, Rhizopus nigricans, Chaetomium
      globosum and Gliocladium species were found primarly whereas at later stages of
      decomposition preponderance of Aspergillus candidus, Torula graminis,
      Cladosporiun cladosporioides and Aspergillus luchuensis was recorded. 

PMID- 24015097
TI  - Enzyme activities and substrate degradation by fungal isolates on cassava waste
      during solid state fermentation.
AB  - The growth and bioconversion potential of selected strains growing on cassava
      waste substrate during solid state fermentation were assessed. Rhizopus
      stolonifer showed the highest and the fastest utilization of starch and cellulose
      in the cassava waste substrate. It showed 70% starch utilization and 81%
      cellulose utilization within eight days. The release of reducing sugars
      indicating the substrate saccharification or degradation potential of the
      organisms reached the highest value of 406.5 mg/g by R. stolonifer on cassava
      waste during the eighth day of fermentation. The protein content was gradually
      increased (89.4 mg/g) on the eighth day of fermentation in cassava waste by R.
      stolonifer. The cellulase and amylase activity is higher in R. stolonifer than A.
      niger and P. chrysosporium. The molecular mass of purified amylase and cellulase
      seemed to be 75 KDal, 85 KDal respectively. 

PMID- 24015098
TI  - Evaluation of White-rot Fungi for Biopulping of Wood.
AB  - Ergosterol involves in fungal cell growth as a major component in fungal cell
      membranes. It can be an indicator that shows the fungal activity, and its content
      depends on the fungal strains, culture, growth conditions and so on. In this
      study, fungal activities and growth patterns of three white-rot fungi strains
      isolated in Korea were evaluated by determination of ergosterol contents during
      the incubation. Wood decay test and chemical analyses of wood were also performed
      to verify the relationship between fungal activity and wood degrading capacity of
      white-rot fungi for 60 days. In the results of experiments, it is considered that
      the test strains selectively degrade large amount of lignin in wood at the early
      stage of decay. Especially, Phanerochaete chrysosporium showed the best
      capability on selective degradation of lignin among the test fungi. It is
      suggested that the determination of ergosterol content in the fungal culture
      during the incubation is the simple and effective screening method of white-rot
      fungi for the application to biopulping of wood. 

PMID- 24015099
TI  - Antibacterial and Antifungal Activities of Stereum ostrea, an Inedible Wild
      Mushroom.
AB  - Antibacterial and antifungal activities of liquid culture filtrate, water and
      ethanol extract (solid culture) of Stereum ostrea were evaluated against 5
      bacteria and 3 plant pathogenic fungi. To determine the minimal inhibitory
      concentration (MIC), we studied 5~300 mg/ml concentrations against bacteria and
      fungi separately. The MIC was 10 mg/ml for Bacillus subtilis and 40 mg/ml for
      Colletotrichum gloeosporioides and Colletotrichum miyabeanus. Liquid culture
      filtrate was more effective against Gram positive than Gram negative bacteria,
      and Staphylococcus aureus was the most inhibited (20.3 mm) bacterium. Water and
      ethanol extracts were effective against both Gram positive and Gram negative
      bacteria, and water extract was better than ethanol extract. In water and ethanol
      extract, inhibition zones were 23.6 and 21.0 mm (S. aureus) and 26.3 and 22.3 mm
      (Pseudomonas aeruginosa), respectively. For plant pathogenic fungi, the highest
      and lowest percent inhibition of mycelial growth (PIMG) was found 82.8 and 14.4
      against C. miyabeanus and Botrytis cinerea in liquid culture filtrate,
      respectively. In water extract, the PIMG was found to be the highest 85.2 and
      lowest 41.7 for C. miyabeanus and C. gloeosporioides, respectively. The
      inhibitory effect of ethanol extract was better against C. miyabeanus than C.
      gloeosporioides and B. cinerea. Among 3 samples, water extract was the best
      against tested pathogenic fungi. This study offers that the extracts isolated
      from S. ostrea contain potential compounds which inhibit the growth of both
      bacteria and fungi. 

PMID- 24015100
TI  - Chemical Components of Paecilomyces tenuipes (Peck) Samson.
AB  - The caterpillar-shaped Chinese medicinal mushroom (DongChongXiaCao) looks like a
      worm in the winter and like a grass in the summer. The fruiting body has been
      regarded as popular folk or effective medicines used to treat human diseases such
      as asthma, bronchial and lung inflammation, and kidney disease. The fruiting
      bodies of Paecilomyces tenuipes that formed on the living silkworm (Bombyx mori)
      host were used in this examination. This study was carried out to investigate the
      proximate composition, soluble sugar, amino acid and fatty acid profiles, and
      contents of the bioactive ingredient including adenosine and D-mannitol in the
      fruiting-bodies. The moisture content was 57.56%. Soluble sugars found were
      glycerol, glucose, mannitol and sucrose, and the contents exceeded 24 mgg(-1)dry
      weight. Total free amino acid content was 17.09 mg g(-1)dry weight. Arginine,
      glycine, proline and tyrosine were main amino acids. The content of oleic acid in
      fatty acids was high. Adenosine was more abundant in fruiting bodies than corpus.

PMID- 24015101
TI  - Purification and Characterization of a Keratinase from a Feather-Degrading
      Fungus, Aspergillus flavus Strain K-03.
AB  - A keratinolytic enzyme secreted by Aspergillus flavus K-03 cultured in feather
      meal basal medium (FMBM) containing 2% (w/v) chicken feather was purified and
      characterized. Keratinolytic enzyme secretion was the maximal at day 16 of the
      incubation period at pH 8 and 28C. No relationship was detected between enzyme
      yield and increase of fungal biomass. The fraction obtained at 80% ammonium
      sulfate saturation showed 2.39-fold purification and was further purified by gel
      filtration in Sephadex G-100 followed by ion exchange chromatography on DEAE
      Sephadex A-50, yielding an active protein peak showing 11.53-fold purification.
      Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and
      zymograms indicated that the purified keratinase is a monomeric enzyme with 31
      kDa molecular weight. The extracellular keratinase of A. flavus was active in a
      board range of pH (7~10) and temperature (30C~70C) profiles with the optimal for
      keratinase activity at pH 8 and 45C. The keratinase activity was totally
      inhibited by protease inhibitors such as phenylmethylsulfonyl fluoride (PMSF),
      iodoacetic acid, and ethylenediaminetetraacetate (EDTA) while no reduction of
      activity by the addition of dithiothreitol (DTT) was observed. N-terminal amino
      acid sequences were up to 80% homologous with the fungal subtilisins produced by
      Fusarium culmorum. Therefore, on the basis of these characteristics, the
      keratinase of A. flavus K-03 is determined to be subtilisins-like. 

PMID- 24015102
TI  - The Artificial Cultivation of Oudemansiella mucida on the Oak Sawdust Medium.
AB  - To produce fruiting bodies of Oudemansiella mucida, porcelain fungus, on the oak
      sawdust medium, additives suitable for the mycelial growth and fruiting body
      formation were screened. In general, the mycelial growth of the three strains of
      O. mucida used in this study have been good on oak sawdust mixed rice bran of
      20~30%. The mycelia incubated in potato dextrose broth for 7 days were inoculated
      on oak sawdust medium supplemented with various ratios of rice bran and incubated
      for 30 days at 25C in the dark condition until the mycelia of O. mucida fully
      colonized the media from top to bottom. Then, top surface of the media in the
      bottles were horizontally scratched with a spatula and filled with tap water for
      3 hours. To induce the primordial formation of O. mucida, the bottles were
      transferred to the mushroom cultivating room under 12 hrs of light (350 lux) and
      dark condition with relative humidity of 95% at 17C. The primordia of O. mucida
      were formed on the surface of oak sawdust media after 7 days of incubation. The
      mature fruiting bodies were observed 5 days after primordial formation. The
      fruiting bodies O. mucida were formed on oak sawdust medium mixed with 5 to 30%
      rice bran. However, abundant fruiting-bodies of O. mucida were produced in oak
      sawdust medium supplemented with 20% rice bran. This is the first report
      associated with an artificial fruiting body production of O. mucida in Korea. 

PMID- 24015103
TI  - Stable Formation of Fruiting Body in Cordyceps bassiana.
AB  - In order to breed a Cordyceps bassiana isolate that stably forms fruiting body in
      artificial cultivation, isolates derived from subculturing and single spores were
      tested through mating. From C. bassiana EFCC 783, three subcultured isolates EFCC
      2830, EFCC 2831 and EFCC 2832 were obtained and fourteen single conidial isolates
      were obtained from these three subcultured isolates. Two different morphological
      types were found in the fourteen single conidial isolates. One type was able to
      form synnemata and another type was not able to form synnemata. Since switch of
      morphological type was not observed despite their continuous subculturing, cross
      was performed between the two types and the formation of fruiting body was
      examined. Ascospores were obtained from a selected fruiting body formed by hybrid
      of the cross. Self-cross and combinational cross of the ascospore-derived
      isolates generated hybrids that stably produce high quality fruiting body in
      artificial media. 

PMID- 24015104
TI  - Occurrence of Narcissus Smoulder Caused by Botrytis narcissicola in Korea.
AB  - Leaf blight and bulb rot symptoms were observed on narcissus plants grown in
      Yongin, Cheongwon and Namhae areas in Korea during disease survey from 1999 to
      2002. A total of 15 isolates of Botrytis sp. were obtained from the infected
      plant parts of narcissus. All the isolates were identified as Botrytis
      narcissicola based on their morphological and cultural characteristics. Three
      isolates of B. narcissicola were tested for their pathogenicity to leaves and
      bulbs of narcissus by artificial inoculation. All the isolates induced leaf
      blight and bulb rot symptoms on the plants of narcissus by artificial
      inoculation. The symptoms induced by artificial inoculation were similar to those
      observed in the fields. This is the first report of narcissus smoulder caused by
      B. narcissicola in Korea. 

PMID- 24015105
TI  - Occurrence of Anthracnose on Fruits of Asian Pear Tree Caused by Colletotrichum
      acutatum.
AB  - Anthracnose symptoms often occurred on fruits of Asian pear trees grown in
      Anseong, Naju, Seonghwan and Pyeongtaek in Korea during the harvesting period
      from 2000 to 2005. A total of 28 isolates of Colletotrichum sp. were obtained
      from the anthracnose symptoms. All the isolates were identified as Colletotrichum
      acutatum based on their morphological and cultural characteristics. Four isolates
      of the fungus were tested for pathogenicity to fruits of Asian pear tree by
      artificial inoculation. All the isolates induced anthracnose symptoms on the
      fruits by wound inoculation but not by unwound inoculation. The anthracnose
      symptoms induced by artificial inoculation were similar to those observed in the
      orchard. This is the first report of anthracnose of Asian pear tree caused by
      Colletotrichum acutatum. 

PMID- 24015106
TI  - Antifungal activity of clove essential oil and its volatile vapour against
      dermatophytic fungi.
AB  - Antifungal activities of clove essential oil and its volatile vapour against
      dermatophytic fungi including Candida albicans, Epidermophyton floccosum.
      Microsporum audouinii, Trichophyton mentagrophytes, and Trichophyton rubrum were
      investigated. Both clove essential oil and its volatile vapour strongly inhibit
      spore germination and mycelial growth of the dermatophytic fungi tested. The
      volatile vapour of clove essential oil showed fungistatic activity whereas direct
      application of clove essential oil showed fungicidal activity. 

PMID- 24015108
TI  - A regionalized national universal kriging model using Partial Least Squares
      regression for estimating annual PM2.5 concentrations in epidemiology.
AB  - Many cohort studies in environmental epidemiology require accurate modeling and
      prediction of fine scale spatial variation in ambient air quality across the U.S.
      This modeling requires the use of small spatial scale geographic or "land use"
      regression covariates and some degree of spatial smoothing. Furthermore, the
      details of the prediction of air quality by land use regression and the spatial
      variation in ambient air quality not explained by this regression should be
      allowed to vary across the continent due to the large scale heterogeneity in
      topography, climate, and sources of air pollution. This paper introduces a
      regionalized national universal kriging model for annual average fine particulate
      matter (PM2.5) monitoring data across the U.S. To take full advantage of an
      extensive database of land use covariates we chose to use the method of Partial
      Least Squares, rather than variable selection, for the regression component of
      the model (the "universal" in "universal kriging") with regression coefficients
      and residual variogram models allowed to vary across three regions defined as
      West Coast, Mountain West, and East. We demonstrate a very high level of cross
      validated accuracy of prediction with an overall R2 of 0.88 and well-calibrated
      predictive intervals. In accord with the spatially varying characteristics of
      PM2.5 on a national scale and differing kriging smoothness parameters, the
      accuracy of the prediction varies by region with predictive intervals being
      notably wider in the West Coast and Mountain West in contrast to the East.

PMID- 24015109
TI  - Ensemble projections of wildfire activity and carbonaceous aerosol concentrations
      over the western United States in the mid-21st century.
AB  - We estimate future wildfire activity over the western United States during the
      mid-21st century (2046-2065), based on results from 15 climate models following
      the A1B scenario. We develop fire prediction models by regressing meteorological
      variables from the current and previous years together with fire indexes onto
      observed regional area burned. The regressions explain 0.25-0.60 of the variance
      in observed annual area burned during 1980-2004, depending on the ecoregion. We
      also parameterize daily area burned with temperature, precipitation, and relative
      humidity. This approach explains ~0.5 of the variance in observed area burned
      over forest ecoregions but shows no predictive capability in the semi-arid
      regions of Nevada and California. By applying the meteorological fields from 15
      climate models to our fire prediction models, we quantify the robustness of our
      wildfire projections at mid-century. We calculate increases of 24-124% in area
      burned using regressions and 63-169% with the parameterization. Our projections
      are most robust in the southwestern desert, where all GCMs predict significant
      (p<0.05) meteorological changes. For forested ecoregions, more GCMs predict
      significant increases in future area burned with the parameterization than with
      the regressions, because the latter approach is sensitive to hydrological
      variables that show large inter-model variability in the climate projections. The
      parameterization predicts that the fire season lengthens by 23 days in the warmer
      and drier climate at mid-century. Using a chemical transport model, we find that
      wildfire emissions will increase summertime surface organic carbon aerosol over
      the western United States by 46-70% and black carbon by 20-27% at midcentury,
      relative to the present day. The pollution is most enhanced during extreme
      episodes: above the 84th percentile of concentrations, OC increases by ~90% and
      BC by ~50%, while visibility decreases from 130 km to 100 km in 32 Federal Class
      1 areas in Rocky Mountains Forest.

PMID- 24015110
TI  - Psychological need satisfaction, intrinsic motivation and affective response to
      exercise in adolescents.
AB  - OBJECTIVES: To further understanding of the factors influencing adolescents'
      motivations for physical activity, the relationship of variables derived from
      Self-Determination Theory to adolescents' affective response to exercise was
      examined. DESIGN: Correlational. METHOD: Adolescents (N = 182) self-reported
      psychological needs satisfaction (perceived competence, relatedness, and
      autonomy) and intrinsic motivation related to exercise. In two clinic visits,
      adolescents reported their affect before, during, and after a moderate-intensity
      and a hard-intensity exercise task. RESULTS: Affective response to exercise and
      psychological needs satisfaction independently contributed to the prediction of
      intrinsic motivation in hierarchical linear regression models. The association
      between affective response to exercise and intrinsic motivation was partially
      mediated by psychological needs satisfaction. CONCLUSIONS: Intrinsic motivation
      for exercise among adolescents may be enhanced when the environment supports
      perceived competence, relatedness, and autonomy, and when adolescents participate
      in activities that they find enjoyable.

PMID- 24015112
TI  - Pediatric AIDS in the elimination agenda.

PMID- 24015111
TI  - Comparative sex chromosome genomics in snakes: differentiation, evolutionary
      strata, and lack of global dosage compensation.
AB  - Snakes exhibit genetic sex determination, with female heterogametic sex
      chromosomes (ZZ males, ZW females). Extensive cytogenetic work has suggested that
      the level of sex chromosome heteromorphism varies among species, with Boidae
      having entirely homomorphic sex chromosomes, Viperidae having completely
      heteromorphic sex chromosomes, and Colubridae showing partial differentiation.
      Here, we take a genomic approach to compare sex chromosome differentiation in
      these three snake families. We identify homomorphic sex chromosomes in boas
      (Boidae), but completely heteromorphic sex chromosomes in both garter snakes
      (Colubridae) and pygmy rattlesnake (Viperidae). Detection of W-linked gametologs
      enables us to establish the presence of evolutionary strata on garter and pygmy
      rattlesnake sex chromosomes where recombination was abolished at different time
      points. Sequence analysis shows that all strata are shared between pygmy
      rattlesnake and garter snake, i.e., recombination was abolished between the sex
      chromosomes before the two lineages diverged. The sex-biased transmission of the
      Z and its hemizygosity in females can impact patterns of molecular evolution, and
      we show that rates of evolution for Z-linked genes are increased relative to
      their pseudoautosomal homologs, both at synonymous and amino acid sites (even
      after controlling for mutational biases). This demonstrates that mutation rates
      are male-biased in snakes (male-driven evolution), but also supports faster-Z
      evolution due to differential selective effects on the Z. Finally, we perform a
      transcriptome analysis in boa and pygmy rattlesnake to establish baseline levels
      of sex-biased expression in homomorphic sex chromosomes, and show that
      heteromorphic ZW chromosomes in rattlesnakes lack chromosome-wide dosage
      compensation. Our study provides the first full scale overview of the evolution
      of snake sex chromosomes at the genomic level, thus greatly expanding our
      knowledge of reptilian and vertebrate sex chromosomes evolution.

PMID- 24015113
TI  - First diagnosis and management of incontinence in older people with and without
      dementia in primary care: a cohort study using The Health Improvement Network
      primary care database.
AB  - BACKGROUND: Dementia is one of the most disabling and burdensome diseases.
      Incontinence in people with dementia is distressing, adds to carer burden, and
      influences decisions to relocate people to care homes. Successful and safe
      management of incontinence in people with dementia presents additional
      challenges. The aim of this study was to investigate the rates of first diagnosis
      in primary care of urinary and faecal incontinence among people aged 60-89 with
      dementia, and the use of medication or indwelling catheters for urinary
      incontinence. METHODS AND FINDINGS: We extracted data on 54,816 people aged 60-89
      with dementia and an age-gender stratified sample of 205,795 people without
      dementia from 2001 to 2010 from The Health Improvement Network (THIN), a United
      Kingdom primary care database. THIN includes data on patients and primary care
      consultations but does not identify care home residents. Rate ratios were
      adjusted for age, sex, and co-morbidity using multilevel Poisson regression. The
      rates of first diagnosis per 1,000 person-years at risk (95% confidence interval)
      for urinary incontinence in the dementia cohort, among men and women,
      respectively, were 42.3 (40.9-43.8) and 33.5 (32.6-34.5). In the non-dementia
      cohort, the rates were 19.8 (19.4-20.3) and 18.6 (18.2-18.9). The rates of first
      diagnosis for faecal incontinence in the dementia cohort were 11.1 (10.4-11.9)
      and 10.1 (9.6-10.6). In the non-dementia cohort, the rates were 3.1 (2.9-3.3) and
      3.6 (3.5-3.8). The adjusted rate ratio for first diagnosis of urinary
      incontinence was 3.2 (2.7-3.7) in men and 2.7 (2.3-3.2) in women, and for faecal
      incontinence was 6.0 (5.1-7.0) in men and 4.5 (3.8-5.2) in women. The adjusted
      rate ratio for pharmacological treatment of urinary incontinence was 2.2 (1.4
      3.7) for both genders, and for indwelling urinary catheters was 1.6 (1.3-1.9) in
      men and 2.3 (1.9-2.8) in women. CONCLUSIONS: Compared with those without a
      dementia diagnosis, those with a dementia diagnosis have approximately three
      times the rate of diagnosis of urinary incontinence, and more than four times the
      rate of faecal incontinence, in UK primary care. The clinical management of
      urinary incontinence in people with dementia with medication and particularly the
      increased use of catheters is concerning and requires further investigation.
      Please see later in the article for the Editors' Summary.

PMID- 24015114
TI  - Calculating the sensitivity and robustness of binding free energy calculations to
      force field parameters.
AB  - Binding free energy calculations offer a thermodynamically rigorous method to
      compute protein-ligand binding, and they depend on empirical force fields with
      hundreds of parameters. We examined the sensitivity of computed binding free
      energies to the ligand's electrostatic and van der Waals parameters. Dielectric
      screening and cancellation of effects between ligand-protein and ligand-solvent
      interactions reduce the parameter sensitivity of binding affinity by 65%,
      compared with interaction strengths computed in the gas-phase. However, multiple
      changes to parameters combine additively on average, which can lead to large
      changes in overall affinity from many small changes to parameters. Using these
      results, we estimate that random, uncorrelated errors in force field nonbonded
      parameters must be smaller than 0.02 e per charge, 0.06 A per radius, and 0.01
      kcal/mol per well depth in order to obtain 68% (one standard deviation)
      confidence that a computed affinity for a moderately-sized lead compound will
      fall within 1 kcal/mol of the true affinity, if these are the only sources of
      error considered.

PMID- 24015115
TI  - Automated Optimization of Potential Parameters.
AB  - An algorithm and software to refine parameters of empirical energy functions
      according to condensed phase experimental measurements are discussed. The
      algorithm is based on sensitivity analysis and local minimization of the
      differences between experiment and simulation as a function of potential
      parameters. It is illustrated for a toy problem of alanine dipeptide and is
      applied to folding of the peptide WAAAH. The helix fraction is highly sensitive
      to the potential parameters while the slope of the melting curve is not. The
      sensitivity variations make it difficult to satisfy both observations
      simultaneously. We conjecture that there is no set of parameters that reproduces
      experimental melting curves of short peptides that are modeled with the usual
      functional form of a force field.

PMID- 24015116
TI  - Optimizing the Pharmacologic Treatment of Insomnia: Current Status and Future
      Horizons.
AB  - A number of medications are available for treating patients with insomnia. These
      medications include agents approved as insomnia therapies by the U.S. Food and
      Drug Administration (FDA), agents approved by the FDA for another condition that
      are used "off-label" to treat insomnia, and agents available "over-the-counter"
      that are taken by individuals with insomnia. These agents differ in their
      properties, their safety and efficacy when used for different insomnia patient
      subtypes, and the available data on their efficacy and safety in these subtypes.
      As a result, optimizing the medication treatment of insomnia for a given patient
      requires that the clinician select an agent for use which has characteristics
      that make it most likely to effectively and safely address the type of sleep
      difficulty experienced by that individual. This article is intended to assist
      clinicians and researchers in carrying out this optimization. It begins by
      reviewing the basic characteristics of the medications used to treat insomnia.
      This is followed by a review of the fundamental ways that individuals with
      insomnia may differ and affect the choice of medication therapy. This review
      includes discussions that illustrate how to best choose a medication based on the
      characteristics of the available medications, the key differences among insomnia
      patients, and the available research literature. Lastly, we discuss future
      directions for the optimizing pharmacologic management of insomnia. It is hoped
      that the treatment tailoring methods discussed herein serve as a means of
      improving the clinical management of insomnia and, thus, improve the lives of the
      many patients who suffer from this common and impairing condition.

PMID- 24015117
TI  - Insomnia and Obstructive Sleep Apnea.

PMID- 24015118
TI  - Focal Infection Treatment using Laser-Mediated Heating of Injectable Silk
      Hydrogels with Gold Nanoparticles.
AB  - Medical treatment of subcutaneous bacterial abscesses usually involves systemic
      high-dose antibiotics and incision-drainage of the wound. Such an approach
      suffers from two main deficiencies: bacterial resistance to antibiotics and pain
      associated with multiple incision-drainage-wound packing procedures. Furthermore,
      the efficacy of high-dose systemic antibiotics is limited because of the
      inability to penetrate into the abscess. To address these obstacles, we present a
      treatment relying on laser-induced heating of gold nanoparticles embedded in an
      injectable silk-protein hydrogel. Although bactericidal nanoparticle systems have
      been previously employed based on silver and nitric oxide, they have limitations
      regarding customization and safety. The method we propose is safe and uses
      biocompatible, highly tunable materials: an injectable silk hydrogel and Au
      nanoparticles, which are effective absorbers at low laser powers such as those
      provided by hand held devices. We demonstrate that a single 10-minute laser
      treatment of a subcutaneous infection in mice preserves the general tissue
      architecture, while achieving a bactericidal effect - even resulting in complete
      eradication in some cases. The unique materials platform presented here can
      provide the basis for an alternative treatment of focal infections.

PMID- 24015119
TI  - Sedation spectrum in endoscopic retrograde cholangiopancreatography: Continuous
      adaptation is the way forward.

PMID- 24015120
TI  - Non-invasive fluid responsiveness monitoring: Patients selection considerations.

PMID- 24015121
TI  - Effects of tranexamic acid during endoscopic sinsus surgery in children.
AB  - OBJECTIVES: This study was conducted to evaluate the effect of tranexamic acid
      (TA) on the intra-operative bleeding during the functional endoscopic sinus
      surgery (FESS) in children. METHODS: A total of 100 children recruited to undergo
      FESS were randomized into two groups. Group I: Was given just after induction,
      intra-venous 25 mg/kg TA diluted in 10 ml of normal saline. Group II: Was given
      10 ml of normal saline. Non-invasive blood pressure, heart rate, and quality of
      the surgical field were estimated every 15 min. Volume of bleeding and duration
      of the surgical procedure were recorded. RESULTS: Surgical field quality after 15
      min revealed that seven patients in group I had minimal bleeding versus no one in
      group II, P=0.006. Meanwhile, 35 patients in group I had mild bleeding versus 26
      patients in group II, P=0.064. Higher number of patients in group II than in
      group I had moderate bleeding, P=0006. Also, at 30 min, revealed that 10 patients
      in group I had minimal bleeding versus one patient in group II, P=0.004.
      Meanwhile, 37 patients in group I had mild bleeding versus 28 patients in group
      II, P=0.059. Higher number of patients in group II than in group I had moderate
      bleeding, P<0001. Duration of the surgeries and volume of bleeding were
      significantly less in tranexamic group than the placebo group, P<0.0001.
      CONCLUSION: Single intra-venous bolus dose of tranexamic in children during the
      FESS improves quality of surgical field, reduces intra-operative bleeding, and
      duration of surgery.

PMID- 24015122
TI  - Effect of hypercapnia on pleth variability index during stable propofol:
      Remifentanil anesthesia.
AB  - BACKGROUND: The pleth variability index (PVI), which is calculated from
      respiratory variations in the perfusion index (PI), has been shown to predict
      fluid responsiveness in mechanically ventilated patients; however, vasomotor tone
      changes induced by hypercapnia can affect PI and hence may slim down the accuracy
      of PVI. This study was designed to find out the impact of mild hypercapnia on
      PVI. METHODS: A total of 30 patients were randomized after induction of general
      anesthesia with target controlled infusion propofol and remifentanil to either
      hypercapnia, (etCO2 =45 mmHg), (group 1, 15 patients) or normocapnia (etCO2 =35
      mmHg) (group 2, 15 patients). After a stabilization period of 10 min, patients
      were crossed over to the other intentional level of etCO2. Heart rate (HR), mean
      arterial pressure (MAP), PI, PVI were collected at the end of each stabilization
      period. RESULTS: Patient characteristics and baseline values of HR, MAP, PI and
      PVI were comparable between the groups. Carryover effect was statistically
      excluded. Hypercapnia significantly increased PI and decreased PVI with
      significant negative correlation. CONCLUSION: Hypercapnia retracts back PVI
      values compared with normocapnia. Precise judgment of fluid responsiveness as
      indicated by PVI necessitates its comparison against similar etCO2 levels.

PMID- 24015123
TI  - Duration of one-lung ventilation stage, POSSUM value and the quality of post
      operative analgesia significantly affect survival and length of stay on intensive
      care unit of patients undergoing two-stage esophagectomy.
AB  - PURPOSE: To analyze different factors affecting the outcome of patients
      undergoing Two Stage Esophagectomy (TSE) for the treatment of esophageal
      carcinoma (EC) while relating these factors to the length of stay on Intensive
      Care Unit (ILOS), mortality, and morbidity. METHODS: Retrospective study of case
      notes of 45 patients who underwent a TSE for resection of EC at a general
      district hospital in the United Kingdom (UK). These procedures were performed by
      the same surgical team and followed same approach, known as the Ivor-Lewis
      procedure. RESULTS: The duration of One Lung Ventilation (OLV) during TSE was
      found to be critical for patient's outcome. Statistical analysis suggested a
      potentially strong effect of the duration of OLV (range: 90-320 minutes) on the
      ILOS (P=0.001). The ratio OLV: Total duration of surgery (TOT) was significantly
      different in early post-operative (PO) deaths (within 3 months) and late deaths
      after the third month (P=0.032). The POSSUM value (Physiological and Operative
      Severity Score for Enumeration of Mortality) correlated well with ILOS (P=0.05).
      Regression analysis showed a strong relationship between the two variables
      (P=0.03). An excellent to good quality of PO analgesia allowed for shorter ILOS
      (P=0.023). CONCLUSIONS: Duration of the OLV appears as an important factor in the
      outcome of patients. POSSUM value could help in planning the post-operative
      critical care need of patients undergoing TSE. A well managed post-operative pain
      allowed to reduce the ILOS.

PMID- 24015124
TI  - A comparison of Truview EVO2 laryngoscope with Macintosh laryngoscope in routine
      airway management: A randomized crossover clinical trial.
AB  - BACKGROUND: The Truview EVO2 blade facilitates the view of vocal cords by
      indirect laryngoscopy and does not require the proper alignment of the oral,
      pharyngeal and tracheal axes as with the Macintosh blade. METHODS: In a crossover
      fashion, we prospectively compared the view obtained at laryngoscopy with Truview
      EVO2 and the Macintosh blade in 110 adult patients of either sex between the age
      of 18 and 60 years, who were scheduled to undergo general anesthesia with
      endotracheal intubation. The patients were intubated with the second
      laryngoscope. The preoperative airway variables, laryngoscopic view, difficulty
      of intubation scale (IDS) score, duration of intubation, and degree of difficulty
      percentage of glottic opening (POGO score) of use with each laryngoscope were
      compared. RESULTS: The IDS score was low and comparable between the two
      laryngoscopes. The laryngeal view was easy; Modified Cormack Lehane (MCL) grade
      2a or less in 98.14% of the cases with the Truview laryngoscope compared to 78.7%
      of the cases with the Macintosh laryngoscope. Nineteen patients of MCL grade 3,
      one patient of grade 2b, and seven patients of grade 2a view with the Macintosh
      laryngoscope had MCL grade 1 view with the Truview laryngoscope. The duration of
      intubation was comparable between Truview and Macintosh laryngoscopes (12.1+/-3.8
      s vs. 10.9+/-2.1 s). CONCLUSION: Truview laryngoscope performed comparably to
      Macintosh laryngoscope in patients with normal airway; however, the Truview
      laryngoscope may be a better option in difficult airway situations when the
      Macintosh blade fails to show the glottic opening.

PMID- 24015125
TI  - Comparative study of intrathecal hyperbaric versus isobaric ropivacaine: A
      randomized control trial.
AB  - BACKGROUND: Hyperbaric ropivacaine produce more reliable sensory and motor block,
      with faster onset, better quality of muscles relaxation than isobaric
      ropivacaine. So, this study was designed to compare the efficacy of hyperbaric
      ropivacaine with isobaric ropivacaine in patients undergoing lower abdominal
      surgery. METHODS: A randomized controlled double blind study in two groups of
      patients. group A (n=35) received 3 ml of isobaric ropivacaine 6 mg/ml (18 mg).
      Group B (n=35) received 3 ml of hyperbaric ropivacaine 6 mg/ml (18 mg). The onset
      and duration of sensory block at dermatome level T10, maximum upper and lower
      spread of sensory block, intensity, and duration of motor block were recorded.
      STATISTICAL ANALYSIS: Block characteristics were compared using the two-tailed
      Mann - Whitney U-test. The proportion of side effects was compared using the Chi
      square test. RESULTS: The median time of onset of sensory block at the T10
      dermatome was 4.4+/-1.3 min in group B and 6.0+/-1.03 min in group A. The median
      time to maximum block height was 16.7+/-3.7 min in group A and 12.03+/-1.96 min
      in group B. The median duration of complete motor recovery (B0) was significantly
      shorter in the heavy ropivacaine group (166.5+/-11.7 min) compared with the
      isobaric ropivacaine group (192.9+/-9.6 min). CONCLUSIONS: Intrathecal hyperbaric
      ropivacaine provides more rapid, adequate, and good quality of sensory and motor
      block with rapid post-operative recovery as compare to isobaric ropivacaine.

PMID- 24015126
TI  - Comparison of the antiemetic effect of ramosetron with the combination of
      dexamethasone and ondansetron in middle ear surgery: A double-blind, randomized
      clinical study.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) is a frequent complication
      of middle ear surgery. Ondansetron has been shown to be effective for early PONV
      and dexamethasone has been shown to be effective for late PONV. Therefore, a
      combination of dexamethasone and ondansetron is commonly used for middle ear
      surgery. This study was conducted to compare the combination of ondansetron and
      dexamethasone with ramosetron for early and late PONV up to 48 h after middle ear
      surgery. METHODS: One hundred and twenty adults scheduled for middle ear surgery
      were allocated to receive either dexamethasone 8 mg and ondansetron 4 mg (n=60)
      or ramosetron 0.3 mg (n=60). General anesthesia with inhalation agents was used
      for all the patients. The incidence and severity of PONV, administration of
      rescue antiemetic, and the side effects of the antiemetic were documented during
      the first 48 h after surgery. RESULTS: The incidence of nausea was significantly
      lower in the dexamethasone and ondansetron group compared to the ramosetron group
      between 2 and 24 h. The complete response, which is patients with no nausea or
      vomiting, was significantly more in dexamethasone and ondansetron group compared
      to ramosetron group between 2 and 24 h and between 24 and 48 h (76% vs. 56%,
      P=0.02, 93% vs. 81%, P=0.05, respectively). Overall, complete response was more
      in dexamethasone and ondansetron group compared to ramosetron group (71% vs. 40%,
      P=0.01). CONCLUSION: The combination of dexamethasone and ondansetron is superior
      to ramosetron for prevention of PONV after middle ear surgeries.

PMID- 24015127
TI  - Outpatient endoscopic retrograde cholangiopancreatography: Safety and efficacy of
      anesthetic management with a natural airway in 653 consecutive procedures.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a unique
      diagnostic and therapeutic procedure performed in high risk patients in
      prone/semi-prone position. Propofol based deep sedation has emerged as the method
      of choice however, the ability to predict possible complications is yet un
      explored. AIMS: The present study aimed to evaluate known high risk-factors for
      general anesthesia (American Society of Anesthesiologists (ASA) status, body mass
      index (BMI), and Mallampati class) for their ability to affect outcomes in ERCP
      patients. STUDY DESIGN: Retrospective data of 653 patients who underwent ERCP
      during a period of 26 months at university hospital of Pennsylvania was reviewed.
      Patient-specific and procedure specific data was extracted. Desaturation was
      defined by fall of pulse oximeter saturation below 95% and its relation to
      patient specific high risk-factors was analyzed. RESULTS: Only 45 patients had
      transient de-saturation below 95% without any residual sequlae. No statistically
      significant relation between desaturation episodes and patients higher ASA status
      or BMI or modified Mallampati (MMP) class was found. Despite 60% patients being
      ASA III/IV none required emergency intubation or procedural interruption. Optimal
      oxygenation and airway patency was maintained with high degree of success using
      simple airway maneuvers or conduit devices (nasal/oral trumpet) with oxygen
      supplementation in all patients. CONCLUSIONS: Unlike general anesthesia, pre
      operative patient ASA status, higher MMP or increasing BMI does not bear relation
      with likelihood of patients desaturating during ERCP. In presence of vigilant
      apnea monitoring and careful dose titration of maintenance anesthetics with
      airway conduits, general anesthesia, emergency intubations, and procedure
      interruptions can be avoided.

PMID- 24015128
TI  - Propofol for laryngeal mask airway insertion in children: Effect of two different
      doses.
AB  - PURPOSE: To compare two different doses of propofol for laryngeal mask airway
      (LMA) insertion in children undergoing out-patient surgeries. BACKGROUND:
      Insertion of LMA just after anesthesia induction is facilitated using propofol.
      However, the optimal dose of this drug not determined yet as heavy doses may lead
      to severe complications, whereas lower doses may not be quite as effective.
      METHODS: In a double-blind randomized clinical trial, 120 children undergoing out
      patient surgeries were recruited to receive intravenous propofol at a dose of
      either 2.5 mg/kg (group 1) or 3.5 mg/kg (group 2) for induction. Intravenous
      midazolam (0.03 mg/kg) and fentanyl (1 MUg/kg) were used as pre-medication in all
      patients and anesthesia induction was initiated using lidocaine (1 mg/kg) prior
      to propofol administration. Hemodynamic changes, probable complications, quality
      of the established airway and number of attempts for LMA insertion were compared
      between two groups. RESULTS: There were no differences in systolic and diastolic
      blood pressure, heart rate, peripheral oxygen saturation and intraoperative
      complications between the groups (P>0.05). LMA insertion was successful at the
      first attempt in 55 (93.2%) and 54 (91.5%) cases in group 1 and group 2,
      respectively (P>0.05). The efficiency of the established airways was adequate in
      all the patients of both groups. CONCLUSION: It seems that propofol doses of 2.5
      and 3.5 mg/kg are equally effective for LMA insertion following intravenous
      midazolam, fentanyl, and lidocaine.

PMID- 24015129
TI  - Dynamics of brain natriuretic peptide in critically ill patients with severe
      sepsis and septic shock.
AB  - PURPOSE: Changes of B-type natriuretic peptide (BNP) in sepsis and its utility in
      predicting intensive care unit outcomes remains a conflicting issue. To
      investigate the changes in plasma levels of BNP in patients with severe
      sepsis/septic shock and to study the association of BNP levels with the severity
      of the disease and prognosis of those patients. METHODS: Thirty patients with
      severe sepsis or septic shock were enrolled in our study. BNP measurements and
      echocardiography were carried out on admission and on 4(th) and 7(th) days. Blood
      concentrations of BNP were measured by commercially available assays (Abbott
      methods). In-hospital mortality and length of stay were recorded multivariate
      analyses adjusted for acute physiology and chronic health evaluation score II
      (APACHE II score) was used for mortality prediction. RESULTS: Twenty patients
      admitted with the diagnosis of severe sepsis and 10 patients with septic shock.
      The in-hospital mortality was 23.3% (7 patients). Admission BNP was significantly
      higher in the non-survivors 1123+/-236.08 versus 592.7+/-347.1 (P<0.001). By
      doing multivariate logestic regression, the predicatable variables for mortality
      was APACHE II score, BNP, and then EF. CONCLUSION: BNP concentrations were
      increased in patients with severe sepsis or septic shock and poor outcome was
      associated with high BNP levels; thus, it may serve as a useful laboratory marker
      to predict survival in these patients.

PMID- 24015130
TI  - Does the Maslach Burnout Inventory correlate with cognitive performance in
      anesthesia practitioners? A pilot study.
AB  - BACKGROUND: Chronic stress is a common condition among health-care operators,
      anesthetists in particular. It is known to cause cognitive weakening and
      pathological outcomes, as the Burnout syndrome. Nevertheless, the impact of
      clinicians' health on their performance has received limited attention thus far.
      Our pilot study, aims at evaluating the influence of burnout on the cognitive
      performance in a population of anesthesia practitioners. METHODS: In 18
      practitioners we assessed attention by means of reaction times (RTs), pre- and
      post-shift, with a five-subtest computerized neuropsychological battery. RTs were
      controlled for the situational anxiety with the State-Trait Anxiety Inventory X1.
      The burnout level was evaluated with the Maslach Burnout Inventory (MBI). The
      three MBI sub-scores (emotional exhaustion, depersonalization and professional
      achievement) were combined to obtain two groups according to the burnout score
      (high and low). RESULTS: Anesthetists showed a significantly worse performance in
      the fifth test post-shift (P=0.041) than pre-shift. The high-score burnout group
      reacted slower than the low-score burnout group in three of the five cognitive
      subtests, without reaching a statistical significance. Nevertheless, our effect
      size, which is independent from the sample size, is very large (d=1.165).
      CONCLUSION: We found that in a population of health-care operators, burnout may
      affect the cognitive and potentially, the working performance. Qualitative and
      quantitative measurements should be integrated to ensure a better management of
      burnout and its consequences in workplaces.

PMID- 24015131
TI  - The effect of addition of intrathecal clonidine to hyperbaric bupivacaine on
      postoperative pain after lower segment caesarean section: A randomized control
      trial.
AB  - BACKGROUND: Intrathecal clonidine prolongs spinal anesthesia but the optimum dose
      to be used in cesarean delivery is not yet known. We evaluated the effect of
      addition of intrathecal clonidine to hyperbaric bupivacaine on postoperative pain
      after lower segment caesarean section. METHODS: A total of 105 parturients
      carrying a singleton fetus at term, scheduled to undergo elective LSCS under
      spinal anesthesia were randomized in a double blind fashion to one of the three
      groups. Group BF (n=35) received 2 ml of 0.5% hyperbaric bupivacaine+25 MUg
      fentanyl, Group BC50 (n=35) received 2 ml of 0.5% hyperbaric bupivacaine+50 MUg
      clonidine, Group BC75 (n=35) received 2 ml of 0.5% hyperbaric bupivacaine+75 MUg
      clonidine. RESULTS: The duration of postoperative analgesia was 184.73+/-68.64
      min in group BF, 360.71+/-86.51 min in group BC50 and 760.50+/-284.03 min in
      group BC75, P<0.001. The incidence of hypotension was comparable, P=0.932,
      whereas the incidence of nausea and pruritis was significantly lower in groups
      BC50 and BC75 as compared to group BF, P<0.001. No other side effects of
      intrathecal clonidine were detected. Neonatal outcome was similar in all the
      three groups. CONCLUSIONS: Addition of 75 MUg clonidine to hyperbaric bupivacaine
      in spinal anesthesia for LSCS significantly prolongs the duration of
      postoperative analgesia without any increase in maternal side effects. There was
      no difference in neonatal outcome.

PMID- 24015132
TI  - Opioid therapy in non-cancer chronic pain patients: Trends and efficacy in
      different types of pain, patients age and gender.
AB  - BACKGROUND: In both developing and developed countries, chronic pain remains a
      real issue and a true disease that affects up to 42% of the population in some
      areas. Opioids are widely used for the management of chronic pain with variations
      in prescribing practices, indications and observed efficacy. AIM: to analyze
      trends in opioids prescribing and patient response in chronic non-cancer pain
      conditions. METHODS: Retrospective study of 1500 casenotes of patients suffering
      variable non-cancer chronic pain conditions. Detailed review of those cases who
      were managed using opioids. Statistical analysis using "SOFA" software set.
      RESULTS: The prevalence of opioids prescribing in patients suffering this
      condition was thus around 35% (n=526). Women older than 50 years were more likely
      than men to have a chronic pain condition and to be given opioid therapy for 1
      year or more. Opioid efficacy on neuropathic and mixed types of pain was found to
      be significant with relatively low rate of drop-out and limited side-effects that
      are not life threatening. Overall, patients stopped or changed their opioid
      medication due to inefficacy in only 12.7% of cases. CONCLUSIONS: The simple fact
      of having pain is itself a source of self-reported disability regardless of the
      actual physiological or pathological mechanism. Policy makers should be aware of
      the huge impact of chronic pain disease and of its serious effects on social and
      economical well-being. In developing countries, chronic pain could represent a
      real challenge for all parties. Multimodal management, including opioids, appears
      crucial for the approach of this disease.

PMID- 24015133
TI  - Prevention of sevoflurane related emergence agitation in children undergoing
      adenotonsillectomy: A comparison of dexmedetomidine and propofol.
AB  - BACKGROUND: Emergence agitation (EA) in children is increased after sevoflurane
      anesthesia. Propofol and dexmedetomidine have been used for prophylactic
      treatment with controversial results. The aim of the present study was to compare
      the effect of a single dose of propofol or dexmedetomidine prior to termination
      of sevoflurane-based anesthesia on the incidence and severity of EA in children.
      METHODS: One hundred and twenty children, American Society of Anesthesiologists I
      II, 2-6 years old undergoing adenotonsillectomy under sevoflurane based
      anesthesia were enrolled in the study. Children were randomly allocated to one of
      the three equal groups: (Group C) received 10 ml saline 0.9%, (Group P) received
      propofol 1 mg/kg or (group D) received dexmedetomidine 0.3 ug/kg(-1). The study
      drugs were administered 5 min before the end of surgery. In post anesthesia care
      unit (PACU), the incidence of EA was assessed with Aonos four point scale and the
      severity of EA was assessed with pediatric anesthesia emergence delirium scale
      upon admission (T0), after 5 min (T5), 15 min (T15) and 30 min (T30). Extubation
      time, emergence time, duration of PACU stay and pain were assessed. RESULTS: The
      incidence and severity of EA were lower in group P and group D compared to group
      C at T0, T5 and T15. The incidence and severity of EA in group P were
      significantly higher than group D at the same times. The incidence and severity
      of EA decreased significantly over time in all groups. The modified Children's
      Hospital of Eastern Ontario Pain Scale was significantly lower in group D
      compared to group C and group P. CONCLUSIONS: Dexmedetomidine 0.3 ug/kg(1) was
      more effective than propofol 1 mg/kg in decreasing the incidence and severity of
      EA, when administered 5 min before the end of surgery in children undergoing
      adenotonsillectomy under sevoflurane anesthesia.

PMID- 24015134
TI  - Prophylactic administration of recombinant activated factor VII in coronary
      revascularization surgery.
AB  - OBJECTIVE: The objective of this clinical trial is to study the effectiveness of
      administering recombinant activated factor VII (rFVIIa) in reducing the amount of
      bleeding and the need for homologous blood and products transfusion in cardiac
      surgical coronary revascularization procedures done under cardiopulmonary bypass
      (CPB). METHODS: In a randomized controlled prospective observational study, 30
      patients were scheduled for elective cardiac revascularization under CPB.
      Patients were randomly allocated into two groups. In Group I (Control group), no
      rFVIIa was administered following CPB. In Group II (Study group), a dose of 90
      ug/Kg of rFVIIa was administered following weaning off CPB. The total amount of
      chest tube drain during the 1(st) 24 h following surgery was recorded as well as
      the qualitative and quantitative assessments of homologous blood and products
      transfusion. Serial analysis of hematological parameters including hemoglobin
      level and coagulation test in a definite data points was done. T0=baseline
      readings prior to CPB, T1=off CPB after protamine administration and before
      administration of the study drug, T2=on Cardiac Intensive Care Unit (CICU)
      admission, T3=12 h post-CICU admission, and T4=24 h post-CICU admission. RESULTS:
      Considering the total chest tube drainage, mean values showed statistically
      significant results with a P value of 0.001. Homologous blood and products
      transfusion were statistically lower in the study group. Regarding the mean
      values for hematological assessment, results showed statistically lower
      International Normalized Ratio values at CICU admission and 12 h post-CICU
      admission with a P value of 0.018 and 0.004, respectively. Also, the Partial
      Thromboplastin Time mean values were statistically lower at same timings with
      estimated P values of 0.04 and 0.001, respectively. CONCLUSION: It is concluded
      that the prophylactic use of rFVIIa in patients undergoing coronary
      revascularization surgery under the management of CPB had a remarkable
      significant results on both the amount of post-operative bleeding and the amount
      of blood and products transfusion.

PMID- 24015135
TI  - Efficacy of diltiazem as an adjunct to lignocaine in intravenous regional
      anesthesia.
AB  - BACKGROUND: Various adjuncts have been used with lignocaine to decrease
      tourniquet pain and prolong post-operative analgesia during intravenous regional
      anesthesia (IVRA). Calcium-channel blockers potentiate the analgesic effect of
      local anesthetics. This study was designed to evaluate the efficacy of diltiazem
      as an adjunct to lignocaine in IVRA with respect to tourniquet tolerance,
      perioperative analgesia, and quality of anesthesia. METHODS: In this prospective,
      randomized, and double-blind study, 40 patients (American Society for
      Anesthesiologists grade I/II) undergoing elective hand surgery under IVRA were
      assigned into two groups of 20 each and administered IVRA either with lignocaine
      3 mg/kg (group Lignocaine (L)) or lignocaine 3 mg/kg plus diltiazem 0.2 mg/kg
      (group Lignocaine-Diltiazem (LD)) with normal saline (total volume-40 ml).
      Hemodynamic parameters, onset of the complete sensory blockade, motor blockade,
      and intraoperative (tourniquet pain) and post-operative Visual Analogue Scale
      scores, total intraoperative and consumption of post-operative fentanyl
      intraoperative were recorded. RESULTS: Sensory block was established in 2.5+/
      0.688 min in group LD verses 5.60+/-0.851 min in group L. Motor blockade was
      established in 8.65+/-0.933 min in group LD and 13.46+/-0.604 min in group L. The
      mean VAS scores >3 were attained early at 30 min (3.1+/-0.912) in group L.
      Patients in group L requested early rescue analgesic at 30+/-8.633 min compared
      with 49.64+/-7.958 min in group LD. CONCLUSIONS: Diltiazem as an adjunct to
      lignocaine provided enhanced intraoperative and post-operative analgesia without
      any significant side effects.

PMID- 24015136
TI  - Survival rate in patients after sudden cardiac arrest at the university hospital
      of northern Norway treated with or without opioids: A retrospective evaluation.
AB  - BACKGROUND: Experimental studies both in vivo and in vitro show significantly
      increased survival rate in animals and in cortical neurons respectively exposed
      to acute hypoxia and pre-treated with opioids compared to non-treated
      counterparts. Thus, the main aim of the study was to examine survival rates in
      patients after sudden cardiac arrest (SCA) in the hospital who were or were not
      treated with opioids before and/or during cardiac pulmonary resuscitation (CPR).
      METHODS: The registry SCA database at the University Hospital of Northern Norway
      (UNN) for the period of January 2006-December 2009 was used to obtain data for
      the evaluation. Inclusion criteria were observed SCA at UNN for patients with
      American Society of Anesthesiologists (ASA) 1-3. Exclusion criteria included ASA
      four to five patients and unobserved SCA. Study patients were divided into two
      groups: Those not treated with opioids and those treated with opioids not more
      then 3 h before and/or during CPR. Survival rate 1, 2, 3 and 28 days post CPR
      were compared for the two groups. RESULTS: A total of 117 patients were
      registered in the SCA database at UNN for the period from January 2006 to
      December 2009. Sixty seven patients were excluded from the study: 17 patients had
      an unknown time of SCA diotabut, two patients had only syncope and 48 were ASA
      four to five patients. A total of 50 ASA one to three patients were included in
      the study, 33 and 17 patients respectively in the control and opioid-treated
      groups. The patients who were treated with opioids before or during CPR had a
      significantly higher 1, 2, 3 and 28 days survival rate as compared to those
      receiving only conventional CPR. The model was adjusted for duration of CPR
      (P=0.047) and treatment with adrenaline (P=0.779) in the groups. Adjusted Odds
      ratio was 0.075 (95% confidence interval (CI): 0.015-0.387). Relative risk of
      fatal outcome in the opioids group was 0.2944 (95% CI: 0.1549-0.5594).
      CONCLUSION: Significantly higher 1, 2, 3 and 28 days survival rate and reduced
      duration of CPR were found in the patients additionally treated with opioids
      compared to ordinary resuscitation. Further prospective, randomized, controlled
      trials are needed to investigate the effects of early administration of opioids
      during CPR on survival and brain function in patients with witnessed in-hospital
      SCA.

PMID- 24015137
TI  - Melatonin in perioperative medicine: Current perspective.
AB  - Melatonin, a new addition to the armamentarium of anesthesiologist, has some
      unique properties that are highly desirable in routine peri-operative care.
      Available clinical data show that preoperative melatonin is as effective as
      benzodiazepines in reducing preoperative anxiety with minimal action on
      psychomotor performance and sleep wake cycle. It may be considered as a safe and
      effective alternative of benzodiazepines as preoperative anxiolytic. It may have
      opioid sparing effect, may reduce intraocular pressure, and have role in
      prevention of postoperative delirium. The short-term administration of melatonin
      is free from significant adverse effects also. 

PMID- 24015138
TI  - Tapentadol hydrochloride: A novel analgesic.
AB  - Tapentadol is a novel, centrally acting analgesic with dual mechanism of action,
      combining mu-opioid receptor agonism with noradrenaline reuptake inhibition in
      the same molecule. It has an improved side effect profile when compared to
      opioids and nonsteroidal anti-inflammatory drugs. The dual mechanism of action
      makes Tapentadol a useful analgesic to treat acute, chronic, and neuropathic
      pain. 

PMID- 24015139
TI  - Bronchoscopy as a rescue therapy in patients with status asthmaticus: Two case
      reports and review of literature.
AB  - Management of status asthmaticus requires more than guidelines-guided therapy.
      Occasionally, uncommon therapeutic interventions and procedures may provide
      significant benefits. The role of bronchoscopy in fatal asthma is still not
      clearly defined. We illustrate two cases of severe status asthmaticus on
      mechanical ventilation who showed remarkable improvement after therapeutic
      bronchoscopy. 

PMID- 24015140
TI  - Fatal pulmonary embolism subsequent to the use of Esmarch bandage and tourniquet:
      A case report and review of literature.
AB  - We report a case of fatal pulmonary embolism (PE) following exsanguinations of
      lower limb in orthopedic surgery. A 30-year-old man was posted for fixation of a
      tibial plateau fracture on the seventh day after injury. Subarchnoid block was
      performed. Esmarch bandage was used for exsanguination of the limb and tourniquet
      was inflated. Within three minutes after tourniquet inflation, the patient became
      unconscious hypotensive, and collapsed. Resuscitation was instituted and
      spontaneous circulation restored. Right ventricular strain pattern on
      transthoracic echocardiography, increased levels of D-dimer, and Doppler
      examination of the lowerlimb confirmed deep venous thrombosis of right femoral
      vessels and PE. In spite of thrombolytic therapy with streptokinase and heparin,
      the patient died on the ninth day after the event. Cases of PE secondary to the
      use of Esmarch bandage and tourniquet are reviewed here to identify the risk
      groups and management of PE. 

PMID- 24015141
TI  - Perioperative care of a patient with neuronal ceroid lipofuscinoses.
AB  - The neuronal ceroid lipofuscinoses (NCL) are a group of inherited, autosomal
      recessive, and progressive neurodegenerative diseases, which result from an
      enzymatic defect or the deficiency of a transmembrane protein, leading to the
      accumulation of lipopigments (lipofuscin) in various tissues. NCL results in the
      impairment of function in several end-organs including the central nervous system
      with loss of cognitive and motor function, myoclonus, and intractable seizures.
      Additional involvement includes the cardiovascular system with arrhythmias and
      bradycardia as well as impairment of thermoregulation leading to perioperative
      hypothermia. Given the complexity of the end-organ involvement and the
      progressive nature of the disorder, the anesthetic care of such patients can be
      challenging. Till date, there are a limited number of reports regarding the
      anesthetic management of patients with NCL. We present an 18-year-old patient
      with NCL who required anesthetic care during replacement of a vagal nerve
      stimulator. Previous reports of anesthetic care for these patients are reviewed,
      the end-organ involvement of NCL discussed, and options for anesthetic care
      presented. 

PMID- 24015142
TI  - Right hypoglossal nerve paralysis after tracheal intubation for aesthetic breast
      surgery.
AB  - Aesthetic and functional complications caused by general anesthesia have been
      rarely described after aesthetic surgery. We report a case of unilateral right
      hypoglossal nerve paralysis following the use of a cuffed endotracheal airway in
      a 24-year-old woman undergoing aesthetic breast surgery. Neurological examination
      and magnetic resonance imaging of the head failed to provide additional insights
      into the cause of the nerve injury. Postoperatively, the patient was carefully
      monitored and made a full recovery within 2 weeks without any pharmacological
      treatment. The transient hypoglossal nerve paralysis seemed to be due to
      neuropraxia. In this patient, we postulate that the right hypoglossal nerve was
      compressed between the endotracheal tube cuff and the hyoid bone, which was
      inflated with 30 cm H2O. Patients undergoing aesthetic surgery must be
      appropriately and adequately informed that postoperative aesthetic and functional
      deficits can occur due to anesthesia as well as the surgery. 

PMID- 24015143
TI  - A simple solution to unexpected kinking of endotracheal tube.
AB  - We report a case of unexpected kinking of endotracheal (ET) tube in an infant who
      was being operated in supine position and positioned away from the anesthetist.
      The usual management mentioned in the literature was unsuccessful. So, a simple
      and unique solution that can be useful in unanticipated kinking of ET tube is
      described. 

PMID- 24015144
TI  - Cardiopulmonary resuscitation in undiagnosed situs inversus totalis in emergency
      department: An intensivist challenge.
AB  - Situs inversus totalis is a rare congenital condition. A 34-year-old woman with
      undiagnosed situs inversus was referred to our emergency department with cardiac
      arrested state. She underwent cardiopulmonary resuscitation (CPR) and
      defibrillation with a modified approach. We faced different challenging aspects
      during intensive care management. Ultrasonography in CPR in our patient was very
      helpful. We restricted our discussion on special aspect of SIT in emergency and
      intensive care unit. 

PMID- 24015145
TI  - Obstetric use of nitroglycerin: Anesthetic implications.
AB  - Nitroglycerin has been used in anesthetic practice for induced hypotension and
      managing perioperative hypertension and myocardial ischemia. Contrary to the
      continuous low dose infusions (5-20 mcg/min) used for the same, intravenous bolus
      dosages are sometimes administered at the behest of obstetricians for removal of
      retained placenta. Use of nitroglycerine in managing retained placenta is
      undertaken as a last resort when other measures fail to relax the uterine smooth
      muscles. Intravenous nitroglycerine relaxes smooth muscle cells by releasing
      nitric oxide thus causing prompt cervico-uterine relaxation. However,
      administration of nitroglycerine in this manner is not without risks which should
      be kept in mind while using it for obstetric purposes. We hereby report a case of
      22-year-old female scheduled for manual removal of placenta where unpredictable
      and unexpected hypoxemia was observed following nitroglycerine administration. 

PMID- 24015146
TI  - Airway management in patient with retropharyngeal cerebrospinal fluid collection
      with pre-existing multiple airway problems.

PMID- 24015147
TI  - Anesthesia for Wolff-Parkinson-White syndrome: A report of two cases.

PMID- 24015148
TI  - Severe bradycardia during scalp nerve block in patient undergoing awake
      craniotomy.

PMID- 24015149
TI  - Are we responsible for the dizzy operating surgeon?

PMID- 24015150
TI  - Reinforced endotracheal tube: A life threatening experience in intensive care
      unit.

PMID- 24015151
TI  - Use of a new curved forceps for McGrath MAC(TM) video laryngoscope to remove a
      foreign body causing airway obstruction.

PMID- 24015152
TI  - Molecular Basis of Insulin Resistance: The Role of IRS and Foxo1 in the Control
      of Diabetes Mellitus and Its Complications.
AB  - Insulin/IGF-1 signaling plays a central role in control of cellular metabolism
      and survival, while insulin receptor substrate (IRS) protein -1 and -2 and
      downstream PI-3 kinase->Akt->Foxo1 signaling cascade play key roles in many
      functions of insulin/IGF-1. Dysregulation of this branch of signaling cascades
      may provide a mechanism for insulin resistance as we observed in cells, animals,
      and even humans. Targeting this branch of IRS->Foxo1 signaling may provide us
      with fundamental strategies for drug development in the future.

PMID- 24015153
TI  - Response of snow-dependent hydrologic extremes to continued global warming.
AB  - Snow accumulation is critical for water availability in the northern hemisphere
      1,2, raising concern that global warming could have important impacts on natural
      and human systems in snow-dependent regions 1,3. Although regional hydrologic
      changes have been observed (e.g., 1,3-5), the time of emergence of extreme
      changes in snow accumulation and melt remains a key unknown for assessing climate
      change impacts 3,6,7. We find that the CMIP5 global climate model ensemble
      exhibits an imminent shift towards low snow years in the northern hemisphere,
      with areas of western North America, northeastern Europe, and the Greater
      Himalaya showing the strongest emergence during the near-term decades and at 2
      degrees C global warming. The occurrence of extremely low snow years becomes
      widespread by the late-21st century, as do the occurrence of extremely high early
      season snowmelt and runoff (implying increasing flood risk), and extremely low
      late-season snowmelt and runoff (implying increasing water stress). Our results
      suggest that many snow-dependent regions of the northern hemisphere are likely to
      experience increasing stress from low snow years within the next three decades,
      and from extreme changes in snow-dominated water resources if global warming
      exceeds 2 degrees C above the pre-industrial baseline.

PMID- 24015154
TI  - Polymerization of Protecting-Group-Free Peptides via ROMP.
AB  - A study was conducted to survey the tolerance of ring-opening metathesis
      polymerization (ROMP) with respect to amino acid (a.a) identity of pentapeptide
      modified norbornene-based monomers. A library of norbornyl-pentapeptides were
      prepared with the general structure, norbornyl-GX2PLX5, where residue 'X' was
      changed at each of the two positions (2 or 5) alternately to consist of the
      natural amino acids F, A, V, R, S, K, N, T, M, Q, H, W, C, Y, E, Q, and D. Each
      peptide monomer, free of protecting groups, was mixed in turn under a standard
      set of polymerization conditions with the ROMP initiator
      (IMesH2)C5H5N)2(Cl)2Ru=CHPh. Two sets of polymerization reactions were performed,
      one with Monomer:Initiator (M:I) ratio of 20:1, and another with M:I of 200:1.
      For the nucleophilic amino acids cysteine and lysine, polymerization reactions
      were quantitatively compared to those of their protected analogues. Furthermore,
      we describe polymerization of macromonomers containing up to 30 a.a. to test for
      tolerance of ROMP to peptide molecular weight. These reactions were studied via
      SEC-MALS and NMR. Finally, with knowledge of sequence scope in hand, we prepared
      a set of enzyme-substrate containing brush polymers and studied them with respect
      to their bioactivity.

PMID- 24015155
TI  - Mechanical strain controls endothelial patterning during angiogenic sprouting.
AB  - Cyclic strain is known to affect endothelial cell phenotype, but its effects on
      neovascular pattern formation remain poorly understood. To examine how cyclic
      strain affects angiogenesis, we designed a stretchable, polydimethylsiloxane
      (PDMS)-based multi-well system that supports a 3D cell culture model of
      angiogenesis, consisting of endothelial cells coated onto microcarrier beads
      embedded in a fibrin gel with a supporting monolayer of smooth muscle cells atop
      the gel. Calibration of the integrated system showed a linear relationship
      between applied strain and strain within the fibrin gel. Capillaries formed in
      unstrained conditions grew radially outward, while 3D constructs subjected to 10%
      cyclic strain at 0.7 Hz sprouted in a direction parallel to the applied strain.
      Removal of the tissue from the strain stimulus eliminated directional sprouting.
      To better understand this directional biasing, the strain field surrounding a
      microcarrier bead was modeled computationally, showing local strain anisotropy
      surrounding a microcarrier. Confocal reflection microscopy revealed only modest
      fiber alignment in regions of the gel close to microcarriers, with no evidence of
      alignment further away. Together, these data showed that externally applied
      cyclic strain can spatially pattern capillaries in a 3D culture, and suggests a
      means to control pattern formation in engineered tissues.

PMID- 24015157
TI  - Recovery of Viable Bacteria from Probiotic Products that Target Oral Health.
AB  - Probiotic therapy has predominantly been directed toward promoting and
      maintaining intestinal health. In recent years, however, probiotic regimens that
      target oral health have appeared on the market. These regimens are often
      delivered in the form of lozenges. Despite the oral health claims made by the
      manufacturers of these products, there is little independent evidence in the
      literature to support such claims. In theory, probiotic organisms can be
      beneficial by several different means including direct inhibition of pathogens
      and boosting of the host immune response, with the underlying assumption that
      these mechanisms require a critical number of viable organisms. In this study,
      five brands of probiotics marketed for oral health were tested for the recovery
      of viable bacteria. For only one brand could viable bacteria be recovered within
      one log of the manufacturer's stated starting amount of bacteria. Nearly a
      billion viable bacteria could be recovered from a lozenge of this brand. The
      other brands claimed similar starting amounts of bacteria at the time of
      manufacture but at least a three-log drop off was observed in the amount of
      viable bacteria recovered from those products. Refrigeration of the probiotics
      significantly improved the recovery for one brand, but recoveries for all but one
      brand remained below the recommended daily dosage for probiotic regimens. It is
      concluded that probiotic brands differ significantly in the quantities of
      bacteria that remain viable with most failing to meet recommended dosage targets.

PMID- 24015156
TI  - Self-Disclosure and Mental Health Service Use in Socially Anxious Adolescents.
AB  - Social anxiety disorder is highly prevalent in adolescence, persistent into
      adulthood, and associated with multiple impairments. Despite the development of
      efficacious treatments for socially anxious youth, few affected adolescents
      receive such treatment. This study examined service use in a sample of high
      school students (n = 1,574), as well as predictors of treatment delay and factors
      associated with adolescents' disclosure of social difficulties. Self-report
      measures of social anxiety and service utilization were administered by study
      staff to 10th- and 11th-grade classrooms across three public high schools.
      Consistent with the literature, results indicated low treatment utilization (14
      %) and lengthy delays in treatment initiation. Symptom severity, impairment, and
      disclosing anxiety to school personnel were significant predictors of service
      utilization. Several demographic and illness-specific factors were associated
      with a higher likelihood of disclosing social discomfort. These findings
      underscore the important role of school personnel in identifying and referring
      youth with anxiety disorders. Implications are discussed for increasing access to
      services, including school-wide screenings and training of school personnel to
      recognize and provide intervention for anxious youth.

PMID- 24015158
TI  - Intrasynovial tendon graft for chronic flexor tendon laceration of the finger: a
      case report.
AB  - We present the case of a patient with flexor digitorum profundus tendon
      laceration at the A2 pulley level caused by an injury to the base of the right
      ring finger by a knife. The patient was treated by flexor tendon reconstruction
      from the palm to the fingertip by using the left second toe flexor tendon as a
      graft, which improved the active range of motion. Further improvement was
      achieved by subsequent tenolysis, which eventually restored nearly normal
      function. Our experience with this case indicates that the intrasynovial tendon
      is a reasonable graft source for the synovial space in fingers and may enable
      restoration of excellent postoperative function. 

PMID- 24015159
TI  - Quantification of vertebral involvement in metastatic spinal disease.
AB  - INTRODUCTION: For patients with a solitary and well-delimitated spinal metastasis
      that resides inside the vertebral body, without vertebral canal invasion, and who
      are in good general health with a long life expectancy, en bloc
      spondylectomy/total vertebrectomy combined with the use of primary stabilizing
      instrumentation has been advocated. However, clinical experience suggests that
      these qualifying conditions occur very rarely. OBJECTIVE: The purpose of this
      paper is to quantify the distribution of vertebral involvement in spinal
      metastases and determine the frequency with which patients can be considered
      candidates for radical surgery (en bloc spondylectomy). METHODS: Consecutive
      patients were classified accordingly to Enneking's and Tomita's schemes for
      grading vertebral involvement of metastases. RESULTS: Fifty-one (51) consecutive
      patients were evaluated. Eighty-three percent of patients presented with the
      involvement of multiple vertebral levels and/or spinal canal invasion.
      CONCLUSION: Because of diffuse vertebral involvement of metastases, no patients
      in this sample were considered to be candidates for radical spondylectomy of
      vertebral metastasis.

PMID- 24015161
TI  - The unusual chance fracture: case report & literature review.
AB  - The Chance fracture represents a spinal lesion caused by a flexion-distraction
      injury pattern. We describe a rare case of a male driver admitted at the
      Emergencies of our Institution, level A Trauma center. The was involved in an
      automobile accident without wearing a seatbelt. Radiological findings of plain
      radiography and computed tomography (CT) demonstrated a horizontal fracture
      extending across the vertebral body to the posterior elements with loss of
      vertebral height at the anterior aspect of T12. Based on these findings, the
      diagnosis of a T12 Chance fracture was established. The patient was treated
      conservatively with a thoracolumbar orthosis, without any subsequent
      disabilities. Although Chance fractures are rare lesions, they should always be
      considered in spinal injuries, even in cases of motor-vehicle accidents where no
      seatbelt is used. 

PMID- 24015160
TI  - Surgical and Biomechanical Perspectives on Osteoarthritis and the ACL Deficient
      Knee: A Critical Review of the Literature.
AB  - This review was undertaken to better understand the debate regarding the issue of
      osteoarthritis associated with anterior cruciate ligament (ACL) injuries, from a
      surgical and biomechanical standpoint. Much of the current debate focuses on
      contributory surgical factors and their relative roles in increasing or
      decreasing the risk of future osteoarthritis development, primarily highlighting
      the controversy over whether reconstructive surgery itself is necessarily
      protective. This review addresses the evolution of ACL reconstruction techniques
      over time, and with a view to thoroughly examine the role of surgery, outcome
      differences in procedural technique are reviewed, with a focus on open versus
      arthroscopic methods, graft choice and the use of a double versus single bundle
      reconstruction technique. Moreover, other potentially important contributory
      factors are identified and discussed, such as intrinsic biomechanical alterations
      sustained at the time of initial injury, and how these may have a more
      significant role with regard to future osteoarthritic changes in the knee than
      previously attributed. 

PMID- 24015162
TI  - A case report of crimean congo hemorrhagic Fever in ostriches in iran.
AB  - Crimean Congo hemorrhagic fever (CCHF) is a viral zoonosis, which is usually
      transmitted via tick bites or close contact with infected blood or tissue. This
      disease can cause a case fatality rate of up to 25%-30% in humans. CCHF Infection
      in birds is less documented. An ostrich can reproduce viruses and can also play
      the role of a mechanical vector, by transporting infected ticks without becoming
      ill. In March 2007, three butchers and one worker in an ostrich farm were
      infected with CCHF in central part of Iran. Considering the role ostriches play
      in transmitting the disease, serum samples from five ostriches of that farm were
      taken and sent to the laboratory for CCHF ELISA tests. The result of the IgG test
      was positive for one (20%) of the ostriches. At the same time, serum samples of
      eight sheep from the same farm were sent for IgG testing, two (25%) of which were
      positive. This was the first report of CCHF infection of an ostrich in Iran and
      tracing CCHF IgG against this ostrich and the afore-mentioned sheep may have
      revealed that the disease in the worker was the cause of transmission of this
      disease from these animals or their ticks. 

PMID- 24015163
TI  - Changes in day 1 post-operative intraocular pressure following sutureless 23
      gauge and conventional 20-gauge pars plana vitrectomy.
AB  - BACKGROUND/AIMS: The benefits associated with transconjunctival sutureless
      vitrectomy techniques are continuing to be defined. The purpose of this study was
      to compare the incidence of extreme changes in day 1 intraocular pressure (IOP)
      following 23-gauge sutureless vitrectomy compared with conventional 20-gauge
      vitrectomy. METHODS: Fifty consecutive 23-gauge and 50 consecutive 20-gauge cases
      were included; eyes with a history of previous vitreoretinal surgery were
      excluded. 23-gauge surgery was completed with passive fluid air exchange where no
      long acting tamponade was indicated. The surgery remained sutureless unless a
      leak was visible at the end of the procedure. Data were collected by
      retrospective case note review. Statistical analysis was carried out using
      Fisher's exact and chi-square tests. RESULTS: Twenty-two percent (11/50) of 23
      gauge vitrectomies required suturing of one or more ports. On the first post
      operative day hypotony (IOP<5mmHg) occurred in 1/50 eyes in the 20- and 23-gauge
      groups. Raised pressure (IOP>21mmHg) occurred in 30% (15/50) of eyes in the 20
      gauge group and 8% (4/50) of eyes in the 23-gauge group; IOP>30mmHg only occurred
      in the 20-gauge group (3/50). CONCLUSION: Fluid air exchange following 23-gauge
      vitrectomy is associated with very low risk of day 1 hypotony. This predominantly
      sutureless technique appears to reduce the incidence and magnitude of early post
      operative IOP elevation compared with conventional 20-gauge vitrectomy.

PMID- 24015164
TI  - Study on the use of dielectrophoresis and electrothermal forces to produce on
      chip micromixers and microconcentrators.
AB  - The present study uses the dielectrophoresis (DEP) and electrothermal (ET) forces
      to develop on-chip micromixers and microconcentrators. A microchannel with
      rectangular array of microelectrodes, patterned either on its bottom surface only
      or on both the top and the bottom surfaces, is considered for the analysis. A
      mathematical model to compute electrical field, temperature field, the fluid
      velocity, and the concentration distributions is developed. Both analytical and
      numerical solutions of standing wave DEP (SWDEP), traveling wave DEP (TWDEP),
      standing wave ET (SWET), and traveling wave ET (TWET) forces along the length and
      the height of the channel are compared. The effects of electrode size and their
      placement in the microsystem on micromixing and microconcentrating performance
      are studied and compared to velocity and concentration profiles. SWDEP forces can
      be used to collect the particles at different locations in the microchannel.
      Under positive and negative DEP effect, the particles are collected at electrode
      edges and away from the electrodes, respectively, irrespective of the position,
      size, and number of electrodes. The location of the concentration region can be
      shifted by changing the electrode position. SWET and TWET forces are used for
      mixing and producing concentration regions by circulating the fluid at a given
      location. The effect of forces can be changed with the applied voltage. The TWDEP
      method is the better method for mixing along the length of the channels among the
      four options explored in the present work. If two layers of particle suspension
      are placed side by side in the channel, triangular electrode configuration can be
      used to mix the suspensions. Triangular and rectangular electrode configurations
      can efficiently mix two layers of particle suspension placed side-by-side and one
      atop-the-other, respectively. Hence, SWDEP forces can be successfully used to
      create microconcentrators, whereas TWDEP, SWET, and TWET can be used to produce
      efficient micromixers in a microfluidic chip. 

PMID- 24015170
TI  - Anxiolytic-like effects of antisauvagine-30 in mice are not mediated by CRF2
      receptors.
AB  - The role of brain corticotropin-releasing factor type 2 (CRF2) receptors in
      behavioral stress responses remains controversial. Conflicting findings suggest
      pro-stress, anti-stress or no effects of impeding CRF2 signaling. Previous
      studies have used antisauvagine-30 as a selective CRF2 antagonist. The present
      study tested the hypotheses that 1) potential anxiolytic-like actions of
      intracerebroventricular (i.c.v.) administration of antisauvagine-30 also are
      present in mice lacking CRF2 receptors and 2) potential anxiolytic-like effects
      of antisauvagine-30 are not shared by the more selective CRF2 antagonist
      astressin2-B. Cannulated, male CRF2 receptor knockout (n = 22) and wildtype
      littermate mice (n = 21) backcrossed onto a C57BL/6J genetic background were
      tested in the marble burying, elevated plus-maze, and shock-induced freezing
      tests following pretreatment (i.c.v.) with vehicle, antisauvagine-30 or
      astressin2-B. Antisauvagine-30 reduced shock-induced freezing equally in wildtype
      and CRF2 knockout mice. In contrast, neither astressin2-B nor CRF2 genotype
      influenced shock-induced freezing. Neither CRF antagonist nor CRF2 genotype
      influenced anxiety-like behavior in the plus-maze or marble burying tests. A
      literature review showed that the typical antisauvagine-30 concentration infused
      in previous intracranial studies (~1 mM) was 3 orders greater than its IC50 to
      block CRF1-mediated cAMP responses and 4 orders greater than its binding
      constants (Kd , Ki ) for CRF1 receptors. Thus, increasing, previously used doses
      of antisauvagine-30 also exert non-CRF2-mediated effects, perhaps via CRF1. The
      results do not support the hypothesis that brain CRF2 receptors tonically promote
      anxiogenic-like behavior. Utilization of CRF2 antagonists, such as astressin2-B,
      at doses that are more subtype-selective, can better clarify the significance of
      brain CRF2 systems in stress-related behavior. 

PMID- 24015171
TI  - Tumor necrosis factor alpha rs1800629 polymorphism and risk of cervical lesions:
      a meta-analysis.
AB  - BACKGROUND: Tumor necrosis factor- alpha (TNF-alpha) is an inflammatory cytokine
      which may play important role on the immune response may control the progression
      of cervical lesions. There is a possible association between TNF-alpha rs1800629
      G/A polymorphism and cervical lesions, but previous studies report conflicting
      results. We performed a meta-analysis to comprehensively assess the association
      between TNF-alpha rs1800629 polymorphism and cervical lesions risk. METHODS:
      Literature searches of Pubmed, Embase, Web of Science, and Wanfang databases were
      performed for all publications on the association between TNF-alpha rs1800629
      polymorphism and cervical lesions through December 15, 2012. The pooled odds
      ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to
      assess the strength of the association. RESULTS: Twenty individual case-control
      studies from 19 publications with a total of 4,146 cases and 4,731 controls were
      finally included into the meta-analysis. Overall, TNF-alpha rs1800629
      polymorphism was significantly associated with increased risk of cervical lesions
      under two main genetic comparison models (For A versus G: OR 1.22, 95%CI 1.04
      1.44, P = 0.017; for AA versus GG: OR 1.32, 95%CI 1.02-1.71, P = 0.034). Subgroup
      analysis by ethnicity further showed that there was a significant association
      between TNF-alpha rs1800629 polymorphism and increased risk of cervical lesions
      in Caucasians but not in Asians. Subgroup analysis by the types of cervical
      lesions showed that there was a significant association between TNF-alpha
      rs1800629 polymorphism and increased risk of cervical cancer (For A versus G: OR
      1.24, 95%CI 1.05-1.47, P = 0.011; for AA versus GG: OR 1.31, 95%CI 1.01-1.70, P =
      0.043; for AA/GA versus GG: OR 1.25, 95%CI 1.01-1.54, P = 0.039). CONCLUSION: The
      meta-analysis suggests that TNF-alpha rs1800629 polymorphism is associated with
      increased risk of cervical lesions, especially in Caucasians.

PMID- 24015172
TI  - Numerical study of boundary layer flow and heat transfer of oldroyd-B nanofluid
      towards a stretching sheet.
AB  - In the present article, we considered two-dimensional steady incompressible
      Oldroyd-B nanofluid flow past a stretching sheet. Using appropriate similarity
      variables, the partial differential equations are transformed to ordinary
      (similarity) equations, which are then solved numerically. The effects of various
      parameters, namely, Deborah numbers [Formula: see text] and [Formula: see text],
      Prandtl parameter [Formula: see text], Brownian motion [Formula: see text],
      thermophoresis parameter [Formula: see text] and Lewis number [Formula: see
      text], on flow and heat transfer are investigated. To see the validity of the
      present results, we have made the comparison of present results with the existing
      literature. 

PMID- 24015174
TI  - Recent changes in glacial area and volume on Tuanjiefeng peak region of Qilian
      Mountains, China.
AB  - Glaciers' runoff in the Qilian Mountains serves as a critical water resource in
      the northern sections of the Gansu province, the northeastern sections of the
      Qinghai province, and the northeastern fringe of the Tibetan Plateau. Changes in
      the glacial area and volume around the highest peak of the Qilian Mountains,
      i.e., Tuanjiefeng Peak, were estimated using multi-temporal remote-sensing images
      and digital elevation models, and all possible sources of uncertainty were
      considered in detail. The total glacier area decreased by 16.1+/-6.34 km(2)
      (9.9+/-3.9%) during 1966 to 2010. The average annual glacier shrinkage was -0.15%
      a(-1) from 1966 to 1995, -0.61% a(-1) from 1995 to 2000, -0.20% a(-1) from 2000
      to 2006, and -0.45% a(-1) from 2006 to 2010. A comparison of glacier surface
      elevations using digital elevation models derived from topographic maps in 1966
      and from the Shuttle Radar Topography Mission in 1999 suggests that 65% of the
      grid cells has decreased, thereby indicating that the glacier thickness has
      declined. The average change in glacier thickness was -7.3+/-1.5 m (-0.21+/-0.04
      m.a(-1)) from 1966 to 1999. Glaciers with northeastern aspects thinned by 8.3+/
      1.4 m from 1966 to 1999, i.e., almost twice as much as those with southwestern
      aspects (4.3+/-1.3 m). The ice volume decreased by 11.72+/-2.38*10(8) m(3) from
      1966 to 1999, which was about 17.4% more than the value calculated from the
      statistical relationship between glacier area and volume. The relationship
      between glacier area change and elevation zone indicates that glacier change is
      not only dominated by climate change but also affected by glacier dynamics, which
      are related to local topography. The varied response of a single glacier to
      climate change indicates that the glacier area change scheme used in some models
      must be improved. 

PMID- 24015173
TI  - Unilateral hindlimb casting induced a delayed generalized muscle atrophy during
      rehabilitation that is prevented by a whey or a high protein diet but not a free
      leucine-enriched diet.
AB  - Sarcopenia is the general muscle mass and strength loss associated with ageing.
      Muscle atrophy could be made worse by exposure to acute periods of
      immobilization, because muscle disuse by itself is a stimulus for atrophy. Using
      a model of unilateral hindlimb casting in old adult rats, we have already
      demonstrated that the primary effect of immobilization was atrophy in the casted
      leg, but was also surprisingly associated with a retarded atrophy in the non
      casted leg during rehabilitation. In search of mechanisms involved in this
      generalized atrophy, we demonstrated in the present study that contrary to pair
      fed non-immobilized control animals, muscle protein synthesis in the non
      immobilized limb was unable to adapt and to respond positively to food intake.
      Because pair-fed control rats did not lose muscle mass, this defect in muscle
      protein synthesis may represent one of the explanation for the muscle mass loss
      observed in the non-immobilized rats. Nevertheless, in order to stimulate protein
      turn over and generate a positive nitrogen balance required to maintain the whole
      muscle mass in immobilized rats, we tested a dietary free leucine supplementation
      (an amino acid known for its stimulatory effect on protein metabolism) during the
      rehabilitation period. Leucine supplementation was able to overcome the anabolic
      resistance in the non-immobilized limb. A greater muscle protein synthesis up
      regulation associated with a stimulation of the mTOR signalling pathway was
      indeed recorded but it remained inefficient to prevent the loss of muscle in the
      non-immobilized limb. By contrast, we demonstrated here that whey protein or high
      protein diets were able to prevent the muscle mass loss of the non-immobilized
      limb by sustaining muscle protein synthesis during the entire rehabilitation
      period. 

PMID- 24015175
TI  - Eye-catching odors: olfaction elicits sustained gazing to faces and eyes in 4
      month-old infants.
AB  - This study investigated whether an odor can affect infants' attention to visually
      presented objects and whether it can selectively direct visual gaze at visual
      targets as a function of their meaning. Four-month-old infants (n = 48) were
      exposed to their mother's body odors while their visual exploration was recorded
      with an eye-movement tracking system. Two groups of infants, who were assigned to
      either an odor condition or a control condition, looked at a scene composed of
      still pictures of faces and cars. As expected, infants looked longer at the faces
      than at the cars but this spontaneous preference for faces was significantly
      enhanced in presence of the odor. As expected also, when looking at the face, the
      infants looked longer at the eyes than at any other facial regions, but, again,
      they looked at the eyes significantly longer in the presence of the odor. Thus, 4
      month-old infants are sensitive to the contextual effects of odors while looking
      at faces. This suggests that early social attention to faces is mediated by
      visual as well as non-visual cues. 

PMID- 24015176
TI  - Naturalistic stimulus structure determines the integration of audiovisual looming
      signals in binocular rivalry.
AB  - Rapid integration of biologically relevant information is crucial for the
      survival of an organism. Most prominently, humans should be biased to attend and
      respond to looming stimuli that signal approaching danger (e.g. predator) and
      hence require rapid action. This psychophysics study used binocular rivalry to
      investigate the perceptual advantage of looming (relative to receding) visual
      signals (i.e. looming bias) and how this bias can be influenced by concurrent
      auditory looming/receding stimuli and the statistical structure of the auditory
      and visual signals. Subjects were dichoptically presented with looming/receding
      visual stimuli that were paired with looming or receding sounds. The visual
      signals conformed to two different statistical structures: (1) a 'simple' random
      dot kinematogram showing a starfield and (2) a "naturalistic" visual Shepard
      stimulus. Likewise, the looming/receding sound was (1) a simple amplitude- and
      frequency-modulated (AM-FM) tone or (2) a complex Shepard tone. Our results show
      that the perceptual looming bias (i.e. the increase in dominance times for
      looming versus receding percepts) is amplified by looming sounds, yet reduced and
      even converted into a receding bias by receding sounds. Moreover, the influence
      of looming/receding sounds on the visual looming bias depends on the statistical
      structure of both the visual and auditory signals. It is enhanced when
      audiovisual signals are Shepard stimuli. In conclusion, visual perception
      prioritizes processing of biologically significant looming stimuli especially
      when paired with looming auditory signals. Critically, these audiovisual
      interactions are amplified for statistically complex signals that are more
      naturalistic and known to engage neural processing at multiple levels of the
      cortical hierarchy. 

PMID- 24015177
TI  - The prevalence and influence factors of inter-ankle systolic blood pressure
      difference in community population.
AB  - AIM: The aim of this study was to investigate the prevalence of interankle
      systolic blood pressure difference (sIAND) and its influencing factors in
      community population. METHODS: This study included 2849 (65.1+/-9.4 y) subjects.
      Blood pressure (BPs) of four limbs was simultaneously measured with 4 electronic
      sphygmomanometers after 10 min rest in supine position. The difference of
      systolic BP (SBP) between two ankles was calculated as DETASBP. The criterion for
      abnormal sIAND was >=10 mmHg of absolute DeltaSBP, in which the criterion for 1o
      sIAND was 10-19 mmHg and for 2o sIAND was >=20 mmHg. Age, gender, smoking,
      hypertension, family histories of hypertension and diabetes were recorded.
      Fasting blood glucose and lipids, circumference of hip and waist, and body mass
      index (BMI) were measured. RESULTS: The SBP was higher in the right ankle than in
      the left ankle (158.9+/-21.8 vs 157.3+/-21.6 mmHg, P<0.05) and mean DeltaSBP was
      6.08+/-6.26 mmHg. Similar difference was found in both genders. The prevalence of
      abnormal was 18.5%, in which, the prevalence 1o sIAND was 15.3% and that of 2o
      sIAND was 3.1%. Multivariate regression analysis showed that age, waist
      circumference and blood glucose level were the positive factors for DeltaSBP. The
      normal upper limit for DeltaSBP was 16.7 mmHg in this population, the prevalence
      of sIAND by>=16 mmHg was 5.8%. CONCLUSION: Aging, hypertension, obesity and
      abnormal glucose metabolism are positive factors for inter-ankle SBP difference.

PMID- 24015178
TI  - Full genome sequencing of Corriparta virus, identifies California mosquito pool
      virus as a member of the Corriparta virus species.
AB  - The species Corriparta virus (CORV), within the genus Orbivirus, family
      Reoviridae, currently contains six virus strains: corriparta virus MRM1 (CORV
      MRM1); CS0109; V654; V370; Acado virus and Jacareacanga virus. However, lack of
      neutralization assays, or reference genome sequence data has prevented further
      analysis of their intra-serogroup/species relationships and identification of
      individual serotypes. We report whole-genome sequence data for CORV-MRM1, which
      was isolated in 1960 in Australia. Comparisons of the conserved, polymerase
      (VP1), sub-core-shell 'T2' and core-surface 'T13' proteins encoded by genome
      segments 1, 2 and 8 (Seg-1, Seg-2 and Seg-8) respectively, show that this virus
      groups with the other mosquito borne orbiviruses. However, highest levels of
      nt/aa sequence identity (75.9%/91.6% in Seg-2/T2: 77.6%/91.7% in Seg-8/T13,
      respectively) were detected between CORV-MRM1 and California mosquito pool virus
      (CMPV), an orbivirus isolated in the USA in 1974, showing that they belong to the
      same virus species. The data presented here identify CMPV as a member of the
      Corriparta virus species and will facilitate identification of additional CORV
      isolates, diagnostic assay design and epidemiological studies. 

PMID- 24015179
TI  - A functional polymorphism in a serotonin transporter gene (5-HTTLPR) interacts
      with 9/11 to predict gun-carrying behavior.
AB  - On September 11, 2001, one of the deadliest terrorist attacks in US history took
      place on American soil and people around the world were impacted in myriad ways.
      Building on prior literature which suggests individuals are more likely to
      purchase a gun for self-protection if they are fearful of being victimized, the
      authors hypothesized that the terrorist attacks of 9/11 would lead to an increase
      in gun carrying among US residents. At the same time, a line of research has
      shown that a polymorphism in the 5-HTT gene (i.e., 5-HTTLPR) interacts with
      environmental stressors to predict a range of psychopathologies and behaviors.
      Thus, it was hypothesized that 9/11 and 5-HTTLPR would interact to predict gun
      carrying. The results supported both hypotheses by revealing a positive
      association between 9/11 and gun carrying (b = .426, odds ratio = 1.531, standard
      error for b = .194, z = 2.196, p = .028) in the full sample of respondents (n =
      15,052) and a statistically significant interaction between 9/11 and 5-HTTLPR in
      the prediction of gun carrying (b = -1.519, odds ratio = .219, standard error for
      b = .703, z = -2.161, p = .031) in the genetic subsample of respondents (n =
      2,350). This is one of the first studies to find an association between 9/11 and
      gun carrying and, more importantly, is the first study to report a gene
      environment interaction (GxE) between a measured gene and a terrorist attack. 

PMID- 24015180
TI  - CTLA4 gene polymorphisms influence the incidence of infection after renal
      transplantation in Chinese recipients.
AB  - BACKGROUND: Immunosuppressive therapy is usually administered following renal
      transplantation to protect the graft from rejection. However, this often causes
      complications such as infections to occur. Single nucleotide polymorphisms (SNPs)
      within the CTLA4 gene, such as -1772T/C (rs733618), +49A/G (rs231775) and +6230
      G/A (rs3087243), can affect graft rejection and the long-term clinical outcome of
      organ transplantation. The role of CTLA4 SNPs in T cell-mediated immunity in
      renal transplantation and association with infection after transplantation is
      unknown. METHODS: In this study, the risk of infection according to CTLA4 SNPs
      was investigated in 304 patients who received kidney graft transplants between
      2008 and 2012. RESULTS: The frequency of the rs4553808 GG genotype was
      significantly higher in recipients with viral infection (14.89%) than in those
      without infections (3.50%) (Bonferroni-adjusted p = 0.005). A significant
      difference (p = 0.001) in patients with the rs4553808 GG genotype from those with
      the AA+AG genotypes was found in the viral cohort using the log-rank test. A
      significant association was found between the rs4553808 genotype and onset of
      viral infection in transplant recipients (p = 0.001). The frequencies of the
      CGTAG and CGCAG haplotypes were significantly higher in the viral infection group
      (9.6% and 5.3%) than in the non-viral infection group (3.8% and 1.4%) (p = 0.0149
      and p = 0.0111). No association between any CTLA4 SNP and bacterial infection was
      found. Multivariate analyses revealed that one risk factor, the use of antibody
      induction therapy (p = 0.007), was associated with bacterial infection, and two
      risk factors, antibody use (p = 0.015) and recipient rs4553808 genotype (p =
      0.001), were associated with viral infection. CONCLUSIONS: The rs4553808 GG
      genotype may be a risk factor for viral infection in kidney transplantation. The
      CTLA4 haplotypes CGTAG and CGCAG were partially associated with the development
      of viral infection in Chinese kidney transplant recipients.

PMID- 24015181
TI  - Hypoxia-inducible factor-1alpha polymorphisms and risk of cancer metastasis: a
      meta-analysis.
AB  - BACKGROUND: HIF-1alpha is a major regulator in tumor progression and metastasis
      which responds to hypoxia. Many studies have demonstrated that hypoxia-inducible
      factor1-alpha (HIF-1alpha) polymorphisms are significantly associated with cancer
      metastasis, but the results are inconsistent. We conducted a comprehensive meta
      analysis to estimate the associations between HIF-1alpha C1772 T polymorphism and
      cancer metastasis. METHODS: Comprehensive searches were conducted on PubMed and
      EMBASE database. Fifteen studies were included in the meta-analysis. We used the
      OR and 95%CI to assess the associations between HIF-1alpha C1772T polymorphism
      and cancer metastasis. Heterogeneity and publication bias were also assessed by Q
      test, I (2), and funnel plot. RESULTS: Totally, fifteen studies including 1239
      cases with metastasis-positive (M+) and 2711 cases with metastasis-negative (M-)
      were performed in this meta-analysis. The results showed that HIF-1a C1772T
      polymorphism was associated with the increased risk of cancer metastasis (T
      allele vs. C allele, OR  = 1.36, 95% CI  = 1.12-1.64; TT+ TC vs. CC, OR  = 1.39,
      95% CI  = 1.13-1.71; TT vs. TC+ CC, OR  = 1.93, 95% CI  = 0.86-4.36). In the
      subgroup analyses, the significant associations remained significant among
      Asians, Caucasians and other cancers in the dominant model. Publication bias was
      not observed in the analysis. CONCLUSIONS: Our results indicate that the HIF
      1alphaC1772T polymorphism T allele may increase the risk of cancer metastasis,
      which might be a potential risk factor of cancer progress.

PMID- 24015182
TI  - Working memory updating function training influenced brain activity.
AB  - Recent studies demonstrated that working memory could be improved by training. We
      recruited healthy adult participants and used adaptive running working memory
      training tasks with a double-blind design, combined with the event-related
      potentials (ERPs) approach, to explore the influence of updating function
      training on brain activity. Participants in the training group underwent training
      for 20 days. Compared with the control group, the training group's accuracy (ACC)
      in the two-back working memory task had no significant differences after
      training, but reaction time (RT) was reduced significantly. Besides, the
      amplitudes of N160 and P300 increased significantly whereas that of P200
      decreased significantly. The results suggest that training could have improved
      the participants' capacity on both inhibitory and updating. 

PMID- 24015183
TI  - Geldanamycin-induced osteosarcoma cell death is associated with hyperacetylation
      and loss of mitochondrial pool of heat shock protein 60 (hsp60).
AB  - Osteosarcoma is one of the most malignant tumors of childhood and adolescence
      that is often resistant to standard chemo- and radio-therapy. Geldanamycin and
      geldanamycin analogs have been recently studied as potential anticancer agents
      for osteosarcoma treatment. Here, for the first time, we have presented novel
      anticancer mechanisms of geldanamycin biological activity. Moreover, we
      demonstrated an association between the effects of geldanamycin on the major heat
      shock proteins (HSPs) and the overall survival of highly metastatic human
      osteosarcoma 143B cells. We demonstrated that the treatment of 143B cells with
      geldanamycin caused a subsequent upregulation of cytoplasmic Hsp90 and Hsp70
      whose activity is at least partly responsible for cancer development and drug
      resistance. On the other hand, geldanamycin induced upregulation of Hsp60 gene
      expression, and a simultaneous loss of hyperacetylated Hsp60 mitochondrial
      protein pool resulting in decreased viability and augmented cancer cell death.
      Hyperacetylation of Hsp60 seems to be associated with anticancer activity of
      geldanamycin. In light of the fact that mitochondrial dysfunction plays a
      critical role in the apoptotic signaling pathway, the presented data may support
      a hypothesis that Hsp60 can be another functional part of mitochondria-related
      acetylome being a potential target for developing novel anticancer strategies. 

PMID- 24015184
TI  - What is the relevance of the tip-apex distance as a predictor of lag screw cut
      out?
AB  - Using a simple mathematical formulation, the relationship between the position of
      the lag screw tip (relevant to both intramedullary and extramedullary devices)
      and the concept of tip-apex distance (TAD) was derived. TAD is widely used in
      operating theaters as a surgical guideline in relation to the fixation of
      trochanteric fractures, and in clinical studies as a predictor of lag screw cut
      out. In order to visualize better this concept, the locus of points having the
      same TAD was plotted and the dependence of TAD on the location of the lag screw
      tip was also reported. It was shown that TAD should be adjusted for the size of
      the femoral head (a variable which varies a lot according to the sex of the
      patient) while no correlation was found between TAD and bone morphometry indices
      obtained from micro-CT data (BV/TV and Tb.Th). Therefore, these results seem to
      suggest that TAD lacks mechanical justification and that predictors which are
      based on mechanical properties, such as bone density, should be investigated
      further. 

PMID- 24015185
TI  - Altered DNA methylation patterns of the H19 differentially methylated region and
      the DAZL gene promoter are associated with defective human sperm.
AB  - DNA methylation disturbance is associated with defective human sperm. However,
      oligozoospermia (OZ) and asthenozoospermia (AZ) usually present together, and the
      relationship between the single-phenotype defects in human sperm and DNA
      methylation is poorly understood. In this study, 20 infertile OZ patients and 20
      infertile AZ patients were compared with 20 fertile normozoospermic men.
      Bisulfate-specific PCR was used to analyze DNA methylation of the H19-DMR and the
      DAZL promoter in these subjects. A similar DNA methylation pattern of the H19-DMR
      was detected in AZ and NZ(control), with only complete methylation and mild
      hypomethylation(<50% unmethylated CpGs) identified, and there was no significant
      difference in the occurrence of these two methylation patterns between AZ and NZ
      (P>0.05). However, the methylation pattern of severe hypomethylation (>50%
      unmethylated CpGs ) and complete unmethylation was only detected in 5 OZ
      patients, and the occurrence of these two methylation patterns was 8.54+/-10.86%
      and 9+/-6.06%, respectively. Loss of DNA methylation of the H19-DMR in the OZ
      patients was found to mainly occur in CTCF-binding site 6, with occurrence of
      18.15+/-14.71%, which was much higher than that in patients with NZ (0.84+/
      2.05%) and AZ (0.58+/-1.77%) (P<0.001).Additional, our data indicated the
      occurrence of >20% methylated clones in the DAZL promoter only in infertile
      patients, there was no significant difference between the AZ and OZ patients in
      the proportion of moderately-to-severely hypermethylated clones (p>0.05). In all
      cases, global sperm genome methylation analyses, using LINE1 transposon as the
      indicator, showed that dysregulation of DNA methylation is specifically
      associated with the H19-DMR and DAZL promoter. Therefore, abnormal DNA
      methylation status of H19-DMR, especially at the CTCF-binding site 6, is closely
      associated with OZ. Abnormal DNA methylation of the DAZL promoter might represent
      an epigenetic marker of male infertility. 

PMID- 24015186
TI  - Comparative phylogenomics of pathogenic and non-pathogenic mycobacterium.
AB  - Mycobacterium species are the source of a variety of infectious diseases in a
      range of hosts. Genome based methods are used to understand the adaptation of
      each pathogenic species to its unique niche. In this work, we report the
      comparison of pathogenic and non-pathogenic Mycobacterium genomes. Phylogenetic
      trees were constructed using sequence of core orthologs, gene content and gene
      order. It is found that the genome based methods can better resolve the inter
      species evolutionary distances compared to the conventional 16S based tree.
      Phylogeny based on gene order highlights distinct evolutionary characteristics as
      compared to the methods based on sequence, as illustrated by the shift in the
      relative position of M. abscessus. This difference in gene order among the
      Mycobacterium species is further investigated using a detailed synteny analysis.
      It is found that while rearrangements between some Mycobacterium genomes are
      local within synteny blocks, few possess global rearrangements across the
      genomes. The study illustrates how a combination of different genome based
      methods is essential to build a robust phylogenetic relationship between closely
      related organisms. 

PMID- 24015187
TI  - The hitchhiking effect of a strongly selected substitution in male germline on
      neutral polymorphism in a monogamy population.
AB  - Comparative genomic studies suggest that a huge number of genes that show the
      strongest evidence for positive selection in human are testis- or sperm-specific
      genes, which are possibly due to germline selection. We propose a novel selection
      model in which the germlines of heterozygous males in a monogamous population are
      under natural selection. Under this model, we study the dynamics of a strongly
      selected substitution in the male germline and its hitch-hiking effect on the
      preexisting linked neutral polymorphism. We show that the expected heterozygosity
      at the neural locus is reduced by [Formula: see text], where c is the
      recombination rate between selected and neutral locus, s is selective coefficient
      of advantageous allele, [Formula: see text] and N is diploid effective population
      size. 

PMID- 24015189
TI  - Identifying probable suicide clusters in wales using national mortality data.
AB  - BACKGROUND: Up to 2% of suicides in young people may occur in clusters i.e.,
      close together in time and space. In early 2008 unprecedented attention was given
      by national and international news media to a suspected suicide cluster among
      young people living in Bridgend, Wales. This paper investigates the strength of
      statistical evidence for this apparent cluster, its size, and temporal and
      geographical limits. METHODS AND FINDINGS: The analysis is based on official
      mortality statistics for Wales for 2000-2009 provided by the UK's Office for
      National Statistics (ONS). Temporo-spatial analysis was performed using Space
      Time Permutation Scan Statistics with SaTScan v9.1 for suicide deaths aged 15 and
      over, with a sub-group analysis focussing on cases aged 15-34 years. These
      analyses were conducted for deaths coded by ONS as: (i) suicide or of
      undetermined intent (probable suicides) and (ii) for a combination of suicide,
      undetermined, and accidental poisoning and hanging (possible suicides). The
      temporo-spatial analysis did not identify any clusters of suicide or undetermined
      intent deaths (probable suicides). However, analysis of all deaths by suicide,
      undetermined intent, accidental poisoning and accidental hanging (possible
      suicides) identified a temporo-spatial cluster (p = 0.029) involving 10 deaths
      amongst 15-34 year olds centred on the County Borough of Bridgend for the period
      27(th) December 2007 to 19(th) February 2008. Less than 1% of possible suicides
      in younger people in Wales in the ten year period were identified as being
      cluster-related. CONCLUSIONS: There was a possible suicide cluster in young
      people in Bridgend between December 2007 and February 2008. This cluster was
      smaller, shorter in duration, and predominantly later than the phenomenon that
      was reported in national and international print media. Further investigation of
      factors leading to the onset and termination of this series of deaths, in
      particular the role of the media, is required.

PMID- 24015188
TI  - HDL-apoA-I exchange: rapid detection and association with atherosclerosis.
AB  - High density lipoprotein (HDL) cholesterol levels are associated with decreased
      risk of cardiovascular disease, but not all HDL are functionally equivalent. A
      primary determinant of HDL functional status is the conformational adaptability
      of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical
      modification of apoA-I, as may occur under conditions of inflammation or
      diabetes, can severely impair HDL function and is associated with the presence of
      cardiovascular disease. Chemical modification of apoA-I also impairs its ability
      to exchange on and off HDL, a critical process in reverse cholesterol transport.
      In this study, we developed a method using electron paramagnetic resonance
      spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we
      measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a
      high fat, high cholesterol diet, as well as human subjects with acute coronary
      syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was
      markedly reduced when atherosclerosis was present, or when the subject carries at
      least one risk factor of cardiovascular disease. These results show that HDL-apoA
      I exchange is a clinically relevant measure of HDL function pertinent to
      cardiovascular disease. 

PMID- 24015191
TI  - No evidence for selection of HIV-1 with enhanced gag-protease or Nef function
      among breakthrough infections in the CAPRISA 004 tenofovir microbicide trial.
AB  - BACKGROUND: Use of antiretroviral-based microbicides for HIV-1 prophylaxis could
      introduce a transmission barrier that inadvertently facilitates the selection of
      fitter viral variants among incident infections. To investigate this, we assessed
      the in vitro function of gag-protease and nef sequences from participants who
      acquired HIV-1 during the CAPRISA 004 1% tenofovir microbicide gel trial. METHODS
      AND RESULTS: We isolated the earliest available gag-protease and nef gene
      sequences from 83 individuals and examined their in vitro function using
      recombinant viral replication capacity assays and surface protein downregulation
      assays, respectively. No major phylogenetic clustering and no significant
      differences in gag-protease or nef function were observed in participants who
      received tenofovir gel versus placebo gel prophylaxis. CONCLUSION: Results
      indicate that the partial protective effects of 1% tenofovir gel use in the
      CAPRISA 004 trial were not offset by selection of transmitted/early HIV-1
      variants with enhanced Gag-Protease or Nef fitness.

PMID- 24015192
TI  - An application of outer membrane protein p6-specific enzyme-linked immunosorbent
      assay for detection of haemophilus influenzae in middle ear fluids and
      nasopharyngeal secretions.
AB  - An enzyme-linked immunosorbent assay specific to outer membrane protein P6 (P6
      ELISA) was applied for detecting Haemophilus influenzae in middle ear fluids
      (MEFs) from acute otitis media (AOM) patients and in nasopharyngeal secretions
      (NPSs) from acute rhinosinusitis patients. P6-ELISA had a sensitivity of 83.3%
      for MEFs and 71.5% for NPSs and a specificity of 85.6% for MEFs and 92.5% for
      NPSs, respectively. Real-time PCR exhibited significant differences in the number
      of ompP1 gene copies among samples determined by P6-ELISA to be positive and
      negative for H. influenzae. However, because the P6-ELISA test has the reactivity
      in Haemophilus species include two commensals H. haemolyticus and H.
      parainfluenzae, it is thus a weak method in order to detect only NTHi correctly.
      Consequently, diagnosis using the P6-ELISA should be based on an overall
      evaluation, including the results of other related examinations and clinical
      symptoms to prevent misleading conclusions in clinical setting. 

PMID- 24015193
TI  - Increased serum and musculotendinous fibrogenic proteins following persistent low
      grade inflammation in a rat model of long-term upper extremity overuse.
AB  - We examined the relationship between grip strength declines and muscle-tendon
      responses induced by long-term performance of a high-repetition, low-force (HRLF)
      reaching task in rats. We hypothesized that grip strength declines would
      correlate with inflammation, fibrosis and degradation in flexor digitorum muscles
      and tendons. Grip strength declined after training, and further in weeks 18 and
      24, in reach limbs of HRLF rats. Flexor digitorum tissues of reach limbs showed
      low-grade increases in inflammatory cytokines: IL-1beta after training and in
      week 18, IL-1alpha in week 18, TNF-alpha and IL-6 after training and in week 24,
      and IL-10 in week 24, with greater increases in tendons than muscles. Similar
      cytokine increases were detected in serum with HRLF: IL-1alpha and IL-10 in week
      18, and TNF-alpha and IL-6 in week 24. Grip strength correlated inversely with IL
      6 in muscles, tendons and serum, and TNF-alpha in muscles and serum. Four
      fibrogenic proteins, TGFB1, CTGF, PDGFab and PDGFbb, and hydroxyproline, a marker
      of collagen synthesis, increased in serum in HRLF weeks 18 or 24, concomitant
      with epitendon thickening, increased muscle and tendon TGFB1 and CTGF. A
      collagenolytic gelatinase, MMP2, increased by week 18 in serum, tendons and
      muscles of HRLF rats. Grip strength correlated inversely with TGFB1 in muscles,
      tendons and serum; with CTGF-immunoreactive fibroblasts in tendons; and with MMP2
      in tendons and serum. Thus, motor declines correlated with low-grade systemic and
      musculotendinous inflammation throughout task performance, and increased
      fibrogenic and degradative proteins with prolonged task performance. Serum TNF
      alpha, IL-6, TGFB1, CTGF and MMP2 may serve as serum biomarkers of work-related
      musculoskeletal disorders, although further studies in humans are needed. 

PMID- 24015195
TI  - Determining airborne concentrations of spatial repellent chemicals in mosquito
      behavior assay systems.
AB  - BACKGROUND: Mosquito behavior assays have been used to evaluate the efficacy of
      vector control interventions to include spatial repellents (SR). Current
      analytical methods are not optimized to determine short duration concentrations
      of SR active ingredients (AI) in air spaces during entomological evaluations. The
      aim of this study was to expand on our previous research to further validate a
      novel air sampling method to detect and quantitate airborne concentrations of a
      SR under laboratory and field conditions. METHODOLOGY/PRINCIPAL FINDINGS: A
      thermal desorption (TD) gas chromatography-mass spectrometry (GC-MS) method was
      used to determine the amount of dichlorodiphenyltrichloroethane (DDT) in samples
      of air. During laboratory experiments, 1 L volumes of air were collected over 10
      min intervals from a three-chamber mosquito behavior assay system. Significantly
      higher levels of airborne DDT were measured in the chamber containing textiles
      treated with DDT compared to chambers free of AI. In the field, 57 samples of air
      were collected from experimental huts with and without DDT for onsite analysis.
      Airborne DDT was detected in samples collected from treated huts. The mean DDT
      air concentrations in these two huts over a period of four days with variable
      ambient temperature were 0.74 ug/m(3) (n = 17; SD = 0.45) and 1.42 ug/m(3) (n =
      30; SD = 0.96). CONCLUSIONS/SIGNIFICANCE: The results from laboratory experiments
      confirmed that significantly different DDT exposure conditions existed in the
      three-chamber system establishing a chemical gradient to evaluate mosquito
      deterrency. The TD GC-MS method addresses a need to measure short-term (<1 h) SR
      concentrations in small volume (<100 L) samples of air and should be considered
      for standard evaluation of airborne AI levels in mosquito behavior assay systems.
      Future studies include the use of TD GC-MS to measure other semi-volatile vector
      control compounds.

PMID- 24015194
TI  - Both PKA and Epac pathways mediate N-acetylcysteine-induced Connexin43
      preservation in rats with myocardial infarction.
AB  - Cardiac remodeling was shown to be associated with reduced gap junction
      expression after myocardial infarction. A reduction in gap junctional proteins
      between myocytes may trigger ventricular arrhythmia. Therefore, we investigated
      whether N-acetylcysteine exerted antiarrhythmic effect by preserving connexin43
      expression in postinfarcted rats, focusing on cAMP downstream molecules such as
      protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac).
      Male Wistar rats after ligating coronary artery were randomized to either
      vehicle, or N-acetylcysteine for 4 weeks starting 24 hours after operation.
      Infarct size was similar between two groups. Compared with vehicle, cAMP levels
      were increased by N-acetylcysteine treatment after infarction. Myocardial
      connexin43 expression was significantly decreased in vehicle-treated infarcted
      rats compared with sham operated rats. Attenuated connexin43 expression and
      function were blunted after administering N-acetylcysteine, assessed by
      immunofluorescent analysis, dye coupling, Western blotting, and real-time
      quantitative RT-PCR of connexin43. Arrhythmic scores during programmed
      stimulation in the N-acetylcysteine-treated rats were significantly lower than
      those treated with vehicle. In an ex vivo study, enhanced connexin43 levels
      afforded by N-acetylcysteine were partially blocked by either H-89 (a PKA
      inhibitor) or brefeldin A (an Epac-signaling inhibitor) and completely blocked
      when H-89 and brefeldin A were given in combination. Addition of either the PKA
      specific activator N6Bz or Epac specific activator 8-CPT did not have additional
      increased connexin43 levels compared with rats treated with lithium chloride
      alone. These findings suggest that N-acetylcysteine protects ventricular
      arrhythmias by attenuating reduced connexin43 expression and function via both
      PKA- and Epac-dependent pathways, which converge through the inactivation of
      glycogen synthase kinase-3beta. 

PMID- 24015196
TI  - Potential elucidation of a novel CTL epitope in HIV-1 protease by the protease
      inhibitor resistance mutation L90M.
AB  - The combination of host immune responses and use of antiretrovirals facilitate
      partial control of human immunodeficiency virus type 1 (HIV-1) infection and
      result in delayed progression to Acquired Immunodeficiency Syndrome (AIDS). Both
      treatment and host immunity impose selection pressures on the highly mutable HIV
      1 genome resulting in antiretroviral resistance and immune escape. Researchers
      have shown that antiretroviral resistance mutations can shape cytotoxic T
      lymphocyte immunity by altering the epitope repertoire of HIV infected cells.
      Here it was discovered that an important antiretroviral resistance mutation, L90M
      in HIV protease, occurs at lower frequencies in hosts that harbor the B*15, B*48
      or A*32 human leukocyte antigen subtypes. A likely reason is the elucidation of
      novel epitopes by L90M. NetMHCPan predictions reveal increased affinity of the
      peptide spanning the HIV protease region, PR 89-97 and PR 90-99 to HLA-B*15/B*48
      and HLA-A*32 respectively due to the L90M substitution. The higher affinity could
      increase the chance of the epitope being presented and recognized by Cytotoxic T
      lymphocytes and perhaps provide additional immunological pressures in the
      presence of antiretroviral attenuating mutations. This evidence supports the
      notion that knowledge of HLA allotypes in HIV infected individuals could augment
      antiretroviral treatment by the elucidation of epitopes due to antiretroviral
      resistance mutations in HIV protease. 

PMID- 24015190
TI  - Mapping the genetic variation of regional brain volumes as explained by all
      common SNPs from the ADNI study.
AB  - Typically twin studies are used to investigate the aggregate effects of genetic
      and environmental influences on brain phenotypic measures. Although some
      phenotypic measures are highly heritable in twin studies, SNPs (single nucleotide
      polymorphisms) identified by genome-wide association studies (GWAS) account for
      only a small fraction of the heritability of these measures. We mapped the
      genetic variation (the proportion of phenotypic variance explained by variation
      among SNPs) of volumes of pre-defined regions across the whole brain, as
      explained by 512,905 SNPs genotyped on 747 adult participants from the
      Alzheimer's Disease Neuroimaging Initiative (ADNI). We found that 85% of the
      variance of intracranial volume (ICV) (p = 0.04) was explained by considering all
      SNPs simultaneously, and after adjusting for ICV, total grey matter (GM) and
      white matter (WM) volumes had genetic variation estimates near zero (p = 0.5). We
      found varying estimates of genetic variation across 93 non-overlapping regions,
      with asymmetry in estimates between the left and right cerebral hemispheres.
      Several regions reported in previous studies to be related to Alzheimer's disease
      progression were estimated to have a large proportion of volumetric variance
      explained by the SNPs. 

PMID- 24015197
TI  - Fabry disease - underestimated in the differential diagnosis of multiple
      sclerosis?
AB  - OBJECTIVE: Fabry disease is a rare X-linked inherited lysosomal storage disorder
      affecting multiple organ systems. It includes central nervous system involvement
      via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms
      and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple
      sclerosis. We present an overview of cases from Fabry centres in Germany
      initially misdiagnosed with multiple sclerosis and report the clinical, MR
      tomographical, and laboratory findings. METHODS: Eleven Fabry patients (one male,
      ten females) initially diagnosed with multiple sclerosis were identified from 187
      patient records (5.9%) and analyzed for presenting symptoms, results of the
      initial diagnostic workup, and the clinical course of the disease. RESULTS: Four
      patients were identified as having a "possible" history of MS, and 7 patients as
      "definite" cases of multiple sclerosis (revised McDonald criteria). On average,
      Fabry disease was diagnosed 8.2 years (+/-9.8 years) after the MS diagnosis, and
      12.8 years after onset of first symptoms (+/-10.3 years). All patients revealed
      white matter lesions on MRI. The lesion pattern and results of cerebrospinal
      fluid examination were inconsistent and non-specific. White matter lesion volumes
      ranged from 8.9 mL to 34.8 mL (mean 17.8 mL+/-11.4 mL). There was no association
      between extra-neurological manifestations or enzyme activity and lesion load.
      CONCLUSION: There are several anamnestic and clinical hints indicating when Fabry
      disease should be considered a relevant differential diagnosis of multiple
      sclerosis, e.g. female patients with asymmetric, confluent white matter lesions
      on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria,
      or lack of intrathecally derived immunoglobulin synthesis.

PMID- 24015198
TI  - Effects of clopidogrel on mortality, cardiovascular and bleeding outcomes in
      patients with chronic kidney disease - data from Taiwan acute coronary syndrome
      full spectrum registry.
AB  - BACKGROUND: The efficacy of clopidogrel is inconclusive in the chronic kidney
      disease (CKD) population with acute coronary syndrome (ACS). Furthermore, CKD
      patients are prone to bleeding with antiplatelet therapy. We investigated the
      efficacy and safety of clopidogrel in patients with ACS and CKD. METHODS: In a
      Taiwan national-wide registry, 2819 ACS patients were enrolled. CKD is defined as
      an estimated glomerular filtration rate of less than 60 ml/min per 1.73 m(2). The
      primary endpoints are the combined outcomes of death, non-fatal myocardial
      infarction and stroke at 12 months. RESULTS: Overall 949 (33.7%) patients had CKD
      and 2660 (94.36%) patients received clopidogrel treatment. CKD is associated with
      increased risk of the primary endpoint at 12 months (HR 2.39, 95% CI 1.82 to
      3.15, p<0.01). Clopidogrel use is associated with reduced risk of the primary
      endpoint at 12 months (HR 0.42, 95% CI: 0.29-0.60, p<0.01). Cox regression
      analysis showed that clopidogrel reduced death and primary endpoints for CKD
      population (HR 0.35, 95% CI: 0.21-0.61 and HR 0.48, 95% CI: 0.30-0.77,
      respectively, both p<0.01). Patients with clopidogrel(-)/CKD(-),
      clopidogrel(+)/CKD(+) and clopidogrel(-)/CKD(+) have 2.4, 3.0 and 10.4 fold risk
      to have primary endpoints compared with those receiving clopidogrel treatment
      without CKD (all p<0.01). Clopidogrel treatment was not associated with increased
      in-hospital Thrombolysis In Myocardial Infarction (TIMI) bleeding in CKD
      population. CONCLUSION: Clopidogrel could decrease mortality and improve
      cardiovascular outcomes without increasing risk of bleeding in ACS patients with
      CKD.

PMID- 24015199
TI  - Microbial life in a fjord: metagenomic analysis of a microbial mat in Chilean
      patagonia.
AB  - The current study describes the taxonomic and functional composition of
      metagenomic sequences obtained from a filamentous microbial mat isolated from the
      Comau fjord, located in the northernmost part of the Chilean Patagonia. The
      taxonomic composition of the microbial community showed a high proportion of
      members of the Gammaproteobacteria, including a high number of sequences that
      were recruited to the genomes of Moritella marina MP-1 and
      Colwelliapsycherythraea 34H, suggesting the presence of populations related to
      these two psychrophilic bacterial species. Functional analysis of the community
      indicated a high proportion of genes coding for the transport and metabolism of
      amino acids, as well as in energy production. Among the energy production
      functions, we found protein-coding genes for sulfate and nitrate reduction, both
      processes associated with Gammaproteobacteria-related sequences. This report
      provides the first examination of the taxonomic composition and genetic diversity
      associated with these conspicuous microbial mat communities and provides a
      framework for future microbial studies in the Comau fjord. 

PMID- 24015200
TI  - Clinical significance of MYT1L gene polymorphisms in Chinese patients with
      gastric cancer.
AB  - BACKGROUND: Myelin transcription factor 1 (MYT1) and its homologue MYT1-like
      (MYT1L) are the two main members of MYT/NZF family transcription factors, which
      are highly related, share a high degree of identity and show similar regulatory
      functions in neural development. There are evidences from several cytology
      experiments showing that MYT1 is associated with carcinoma. METHODOLOGY/PRINCIPAL
      FINDINGS: In the present study, we genotyped 944 surgically resected gastric
      cancer patients by the SNaPshot method to explore the association of MYT1L
      rs17039396 polymorphism with survival of gastric cancer in a Chinese population.
      We found that cardia cancer patients carrying MYT1L rs17039396 GG genotype
      survived for a significantly shorter time than those carrying the GA genotype.
      This significance was enhanced in the dominant model (GG vs. GA/AA, log-rank P =
      0.001), suggesting a potential protect role of the variant A allele. Multivariate
      Cox regression analyses showed that the AG/GG genotypes were associated with a
      significantly decreased risk of death from gastric cancer (adjusted hazard ratio
      (HR) = 0.57, 95% confidence interval (CI) = 0.40-0.81). Stratification analyses
      further showed that such protective effect was statistically significant in
      subgroups of patients with tumor size <=5 cm (adjusted HR = 0.34, 95%CI = 0.19
      0.64), well-moderate gastric cancer (adjusted HR = 0.59, 95%CI = 0.35-0.98), no
      lymph-node metastasis (adjusted HR = 0.49, 95%CI = 0.31-0.76), no distant
      metastasis (adjusted HR = 0.59, 95%CI = 0.41-0.84). CONCLUSIONS/SIGNIFICANCE: In
      conclusion, these data represents the first demonstration that MYT1L rs17039396
      variants could indentified as a favorable prognostic indicator for gastric
      cancer, particularly among the cardia gastric cancer. Further validation in other
      larger studies with different ethnic populations and functional evaluations are
      needed.

PMID- 24015202
TI  - Mood and the market: can press reports of investors' mood predict stock prices?
AB  - We examined whether press reports on the collective mood of investors can predict
      changes in stock prices. We collected data on the use of emotion words in
      newspaper reports on traders' affect, coded these emotion words according to
      their location on an affective circumplex in terms of pleasantness and activation
      level, and created indices of collective mood for each trading day. Then, by
      using time series analyses, we examined whether these mood indices, depicting
      investors' emotion on a given trading day, could predict the next day's opening
      price of the stock market. The strongest findings showed that activated pleasant
      mood predicted increases in NASDAQ prices, while activated unpleasant mood
      predicted decreases in NASDAQ prices. We conclude that both valence and
      activation levels of collective mood are important in predicting trend
      continuation in stock prices. 

PMID- 24015201
TI  - Effects of pleiotrophin overexpression on mouse skeletal muscles in normal
      loading and in actual and simulated microgravity.
AB  - Pleiotrophin (PTN) is a widespread cytokine involved in bone formation, neurite
      outgrowth, and angiogenesis. In skeletal muscle, PTN is upregulated during
      myogenesis, post-synaptic induction, and regeneration after crushing, but little
      is known regarding its effects on muscle function. Here, we describe the effects
      of PTN on the slow-twitch soleus and fast-twitch extensor digitorum longus (EDL)
      muscles in mice over-expressing PTN under the control of a bone promoter. The
      mice were maintained in normal loading or disuse condition, induced by hindlimb
      unloading (HU) for 14 days. Effects of exposition to near-zero gravity during a 3
      months spaceflight (SF) into the Mice Drawer System are also reported. In normal
      loading, PTN overexpression had no effect on muscle fiber cross-sectional area,
      but shifted soleus muscle toward a slower phenotype, as shown by an increased
      number of oxidative type 1 fibers, and increased gene expression of cytochrome c
      oxidase subunit IV and citrate synthase. The cytokine increased soleus and EDL
      capillary-to-fiber ratio. PTN overexpression did not prevent soleus muscle
      atrophy, slow-to-fast transition, and capillary regression induced by SF and HU.
      Nevertheless, PTN exerted various effects on sarcolemma ion channel
      expression/function and resting cytosolic Ca(2+) concentration in soleus and EDL
      muscles, in normal loading and after HU. In conclusion, the results show very
      similar effects of HU and SF on mouse soleus muscle, including activation of
      specific gene programs. The EDL muscle is able to counterbalance this latter,
      probably by activating compensatory mechanisms. The numerous effects of PTN on
      muscle gene expression and functional parameters demonstrate the sensitivity of
      muscle fibers to the cytokine. Although little benefit was found in HU muscle
      disuse, PTN may emerge useful in various muscle diseases, because it exerts
      synergetic actions on muscle fibers and vessels, which could enforce oxidative
      metabolism and ameliorate muscle performance. 

PMID- 24015203
TI  - Hypothermia activates adipose tissue to promote malignant lung cancer
      progression.
AB  - Microenvironment has been increasingly recognized as a critical regulator of
      cancer progression. In this study, we identified early changes in the
      microenvironment that contribute to malignant progression. Exposure of human
      bronchial epithelial cells (BEAS-2B) to methylnitrosourea (MNU) caused a
      reduction in cell toxicity and an increase in clonogenic capacity when the
      temperature was lowered from 37 degrees C to 28 degrees C. Hypothermia-incubated
      adipocyte media promoted proliferation in A549 cells. Although a hypothermic
      environment could increase urethane-induced tumor counts and Lewis lung cancer
      (LLC) metastasis in lungs of three breeds of mice, an increase in tumor size
      could be discerned only in obese mice housed in hypothermia. Similarly,
      coinjections using differentiated adipocytes and A549 cells promoted tumor
      development in athymic nude mice when adipocytes were cultured at 28 degrees C.
      Conversely, fat removal suppressed tumor growth in obese C57BL/6 mice inoculated
      with LLC cells. Further studies show hypothermia promotes a MNU-induced
      epithelial-mesenchymal transition (EMT) and protects the tumor cell against
      immune control by TGF-beta1 upregulation. We also found that activated adipocytes
      trigger tumor cell proliferation by increasing either TNF-alpha or VEGF levels.
      These results suggest that hypothermia activates adipocytes to stimulate tumor
      boost and play critical determinant roles in malignant progression. 

PMID- 24015204
TI  - 2-hydroxy arachidonic acid: a new non-steroidal anti-inflammatory drug.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are a family of COX1
      and COX2 inhibitors used to reduce the synthesis of pro-inflammatory mediators.
      In addition, inflammation often leads to a harmful generation of nitric oxide.
      Efforts are being done in discovering safer NSAIDs molecules capable of
      inhibiting the synthesis of pro-inflammatory lipid mediators and nitric oxide to
      reduce the side effects associated with long term therapies.
      METHODOLOGY/PRINCIPAL FINDINGS: The analogue of arachidonic acid (AA), 2-hydroxy
      arachidonic acid (2OAA), was designed to inhibit the activities of COX1 and COX2
      and it was predicted to have similar binding energies as AA for the catalytic
      sites of COX1 and COX2. The interaction of AA and 2OAA with COX1 and COX2 was
      investigated calculating the free energy of binding and the Fukui function.
      Toxicity was determined in mouse microglial BV-2 cells. COX1 and COX2 (PGH2
      production) activities were measured in vitro. COX1 and COX2 expression in human
      macrophage-like U937 cells were carried out by Western blot, immunocytochemistry
      and RT-PCR analysis. NO production (Griess method) and iNOS (Western blot) were
      determined in mouse microglial BV-2 cells. The comparative efficacy of 2OAA,
      ibuprofen and cortisone in lowering TNF-alpha serum levels was determined in
      C57BL6/J mice challenged with LPS. We show that the presence of the -OH group
      reduces the likelihood of 2OAA being subjected to H* abstraction in COX, without
      altering significantly the free energy of binding. The 2OAA inhibited COX1 and
      COX2 activities and the expression of COX2 in human U937 derived macrophages
      challenged with LPS. In addition, 2OAA inhibited iNOS expression and the
      production of NO in BV-2 microglial cells. Finally, oral administration of 2OAA
      decreased the plasma TNF-alpha levels in vivo. CONCLUSION/SIGNIFICANCE: These
      findings demonstrate the potential of 2OAA as a NSAID.

PMID- 24015205
TI  - Protein kinase C zeta regulates human pancreatic cancer cell transformed growth
      and invasion through a STAT3-dependent mechanism.
AB  - Pancreatic cancer is a very aggressive disease with few therapeutic options. In
      this study, we investigate the role of protein kinase C zeta (PKCzeta) in
      pancreatic cancer cells. PKCzeta has been shown to act as either a tumor
      suppressor or tumor promoter depending upon the cellular context. We find that
      PKCzeta expression is either maintained or elevated in primary human pancreatic
      tumors, but is never lost, consistent with PKCzeta playing a promotive role in
      the pancreatic cancer phenotype. Genetic inhibition of PKCzeta reduced adherent
      growth, cell survival and anchorage-independent growth of human pancreatic cancer
      cells in vitro. Furthermore, PKCzeta inhibition reduced orthotopic tumor size in
      vivo by inhibiting tumor cell proliferation and increasing tumor necrosis. In
      addition, PKCzeta inhibition reduced tumor metastases in vivo, and caused a
      corresponding reduction in pancreatic cancer cell invasion in vitro. Signal
      transducer and activator of transcription 3 (STAT3) is often constitutively
      active in pancreatic cancer, and plays an important role in pancreatic cancer
      cell survival and metastasis. Interestingly, inhibition of PKCzeta significantly
      reduced constitutive STAT3 activation in pancreatic cancer cells in vitro and in
      vivo. Pharmacologic inhibition of STAT3 mimicked the phenotype of PKCzeta
      inhibition, and expression of a constitutively active STAT3 construct rescued the
      transformed phenotype in PKCzeta-deficient cells. We conclude that PKCzeta is
      required for pancreatic cancer cell transformed growth and invasion in vitro and
      tumorigenesis in vivo, and that STAT3 is an important downstream mediator of the
      pro-carcinogenic effects of PKCzeta in pancreatic cancer cells. 

PMID- 24015206
TI  - Trait associations across evolutionary time within a drosophila phylogeny:
      correlated selection or genetic constraint?
AB  - Traits do not evolve independently. To understand how trait changes under
      selection might constrain adaptive changes, phenotypic and genetic correlations
      are typically considered within species, but these capture constraints across a
      few generations rather than evolutionary time. For longer-term constraints,
      comparisons are needed across species but associations may arise because of
      correlated selection pressures rather than genetic interactions. Implementing a
      unique approach, we use known patterns of selection to separate likely trait
      correlations arising due to correlated selection from those reflecting genetic
      constraints. We examined the evolution of stress resistance in >90 Drosophila
      species adapted to a range of environments, while controlling for phylogeny.
      Initially we examined the role of climate and phylogeny in shaping the evolution
      of starvation and body size, two traits previously not examined in this context.
      Following correction for phylogeny only a weak relationship between climate and
      starvation resistance was detected, while all of the variation in the
      relationship between body size and climate could be attributed to phylogeny.
      Species were divided into three environmental groups (hot and dry, hot and wet,
      cold) with the expectation that, if genetic correlations underpin trait
      correlations, these would persist irrespective of the environment, whereas
      selection-driven evolution should produce correlations dependent on the
      environment. We found positive associations between most traits in hot and dry
      environments coupled with high trait means. In contrast few trait correlations
      were observed in hot/wet and cold environments. These results suggest trait
      associations are primarily driven by correlated selection rather than genetic
      interactions, highlighting that such interactions are unlikely to limit evolution
      of stress resistance. 

PMID- 24015207
TI  - The immune response of hemocytes of the insect Oncopeltus fasciatus against the
      flagellate Phytomonas serpens.
AB  - The genus Phytomonas includes parasites that are etiological agents of important
      plant diseases, especially in Central and South America. These parasites are
      transmitted to plants via the bite of an infected phytophagous hemipteran.
      Despite the economic impact of these parasites, many basic questions regarding
      the genus Phytomonas remain unanswered, such as the mechanism by which the
      parasites cope with the immune response of the insect vector. In this report,
      using a model of systemic infection, we describe the function of Oncopeltus
      fasciatus hemocytes in the immune response towards the tomato parasite Phytomonas
      serpens. Hemocytes respond to infection by trapping parasites in nodular
      structures and phagocytizing the parasites. In electron microscopy of hemocytes,
      parasites were located inside vacuoles, which appear fused with lysosomes. The
      parasites reached the O. fasciatus salivary glands at least six hours post
      infection. After 72 hours post-infection, many parasites were attached to the
      salivary gland outer surface. Thus, the cellular responses did not kill all the
      parasites. 

PMID- 24015208
TI  - Prenatal antidepressant exposure and risk of spontaneous abortion - a population
      based study.
AB  - PURPOSE: To estimate the risk of spontaneous abortion after use of antidepressant
      medication during pregnancy. METHODS: From the Danish Medical Birth Registry and
      the Danish National Hospital Registry, we identified all pregnancies leading to
      in- or outpatient contacts in Denmark from February 1997 to December 2008. The
      Danish Registry of Medicinal Product Statistics provided information on the
      women's prescriptions for antidepressants during pregnancy. We obtained
      information on women who were diagnosed with depression from the Danish
      Psychiatric Central Registry. Adjusted relative risks (aRR) of spontaneous
      abortion were estimated according to exposure to antidepressants or maternal
      depression using binomial regression. RESULTS: Of the 1,005,319 pregnancies
      (547,300 women) identified, 114,721 (11.4%) ended in a spontaneous abortion. We
      identified 22,061 pregnancies exposed to antidepressants and 1,843 with a
      diagnosis of depression with no antidepressant use, of which 2,637 (12.0%) and
      205 (11.1%) ended in a spontaneous abortion, respectively. Antidepressant
      exposure was associated with an aRR of 1.14 (95% confidence interval (CI) 1.10
      1.18) for spontaneous abortion compared with no exposure to antidepressants.
      Among women with a diagnosis of depression, the aRR for spontaneous abortion
      after any antidepressant exposure was 1.00 (95% CI 0.80-1.24). No individual
      selective serotonin reuptake inhibitor (SSRI) was associated with spontaneous
      abortions. In unadjusted analyses, we found that mirtazapine, venlafaxine, and
      duloxetine were associated with spontaneous abortions among women with depression
      but we had no information on potential differences in disease severity and only
      few pregnancies were exposed in the population. CONCLUSION: We identified a
      slightly increased risk of spontaneous abortion associated with the use of
      antidepressants during pregnancy. However, among women with a diagnosis of
      depression, antidepressants in general or individual SSRI in particular were not
      associated with spontaneous abortions. Further studies are warranted on the newer
      non-SSRI antidepressants, as we had insufficient data to adjust for important
      confounding factors.

PMID- 24015209
TI  - Identification of altered plasma proteins by proteomic study in valvular heart
      diseases and the potential clinical significance.
AB  - BACKGROUND: Little is known about genetic basis and proteomics in valvular heart
      disease (VHD) including rheumatic (RVD) and degenerative (DVD) valvular disease.
      The present proteomic study examined the hypothesis that certain proteins may be
      associated with the pathological changes in the plasma of VHD patients. METHODS
      AND RESULTS: Differential protein analysis in the plasma identified 18
      differentially expressed protein spots and 14 corresponding proteins or
      polypeptides by two-dimensional electrophoresis and mass spectrometry in 120
      subjects. Two up-regulated (complement C4A and carbonic anhydrase 1) and three
      down-regulated proteins (serotransferrin, alpha-1-antichymotrypsin, and
      vitronectin) were validated by ELISA in enlarging samples. The plasma levels (n =
      40 for each) of complement C4A in RVD (715.8+/-35.6 vs. 594.7+/-28.2 ng/ml, P =
      0.009) and carbonic anhydrase 1 (237.70+/-15.7 vs. 184.7+/-10.8 U/L, P = 0.007)
      in DVD patients were significantly higher and that of serotransferrin (2.36+/
      0.20 vs. 2.93+/-0.16 mg/ml, P = 0.025) and alpha-1-antichymotrypsin (370.0+/-13.7
      vs. 413.0+/-11.6 ug/ml, P = 0.019) in RVD patients were significantly lower than
      those in controls. The plasma vitronectin level in both RVD (281.3+/-11.0 vs.
      323.2+/-10.0 ug/ml, P = 0.006) and DVD (283.6+/-11.4 vs. 323.2+/-10.0 ug/ml, P =
      0.011) was significantly lower than those in normal controls. CONCLUSIONS: We
      have for the first time identified alterations of 14 differential proteins or
      polypeptides in the plasma of patients with various VHD. The elevation of plasma
      complement C4A in RVD and carbonic anhydrase 1 in DVD and the decrease of
      serotransferrin and alpha-1-antichymotrypsin in RVD patients may be useful
      biomarkers for these valvular diseases. The decreased plasma level of vitronectin
      - a protein related to the formation of valvular structure - in both RVD and DVD
      patients might indicate the possible genetic deficiency in these patients.

PMID- 24015210
TI  - A CNGB1 frameshift mutation in Papillon and Phalene dogs with progressive retinal
      atrophy.
AB  - Progressive retinal degenerations are the most common causes of complete
      blindness both in human and in dogs. Canine progressive retinal atrophy (PRA) or
      degeneration resembles human retinitis pigmentosa (RP) and is characterized by a
      progressive loss of rod photoreceptor cells followed by a loss of cone function.
      The primary clinical signs are detected as vision impairment in a dim light.
      Although several genes have been associated with PRAs, there are still PRAs of
      unknown genetic cause in many breeds, including Papillons and Phalenes. We have
      performed a genome wide association and linkage studies in cohort of 6 affected
      Papillons and Phalenes and 14 healthy control dogs to map a novel PRA locus on
      canine chromosome 2, with a 1.9 Mb shared homozygous region in the affected dogs.
      Parallel exome sequencing of a trio identified an indel mutation, including a 1
      bp deletion, followed by a 6-bp insertion in the CNGB1 gene. This mutation causes
      a frameshift and premature stop codon leading to probable nonsense mediated decay
      (NMD) of the CNGB1 mRNA. The mutation segregated with the disease and was
      confirmed in a larger cohort of 145 Papillons and Phalenes (PFisher = 1.4*10(-8))
      with a carrier frequency of 17.2 %. This breed specific mutation was not present
      in 334 healthy dogs from 10 other breeds or 121 PRA affected dogs from 44 other
      breeds. CNGB1 is important for the photoreceptor cell function its defects have
      been previously associated with retinal degeneration in both human and mouse. Our
      study indicates that a frameshift mutation in CNGB1 is a cause of PRA in
      Papillons and Phalenes and establishes the breed as a large functional animal
      model for further characterization of retinal CNGB1 biology and possible retinal
      gene therapy trials. This study enables also the development of a genetic test
      for breeding purposes. 

PMID- 24015211
TI  - A meta-analysis of the association between the CC chemokine ligand 5 (CCL5) -403
      G>A gene polymorphism and tuberculosis susceptibility.
AB  - AIM: Many case-control studies have been performed in the recent past to
      investigate the association between CCL5 -403 G>A (rs2107538) gene polymorphism
      and tuberculosis (TB) susceptibility in various ethnic groups. However, these
      studies have produced inconsistent and contradictory results. In the present
      study, meta-analysis was performed to assess the association between CCL5 -403
      G>A polymorphism and TB risk. METHODOLOGY: Quantitative synthesis was done for
      the published studies based upon association between CCL5 -403 G>A polymorphism
      and TB risk from PubMed (Medline), EMBASE web search. Pooled odds ratios (ORs)
      and 95% confidence intervals (95% CIs) were calculated for allele contrast,
      homozygous, heterozygous, dominant and recessive genetic models. RESULTS: A total
      of six studies comprising 1638 confirmed TB cases and 1519 healthy controls were
      included in this meta-analysis. Variant A allele (A vs. G: p = 0.035; OR = 1.301,
      95% CI = 1.019 to 1.662) and variant homozygous (AA vs. GG; p = 0.001; OR =
      1.520, 95% CI = 1.202 to 1.923) carriers were significantly associated with TB
      susceptibility. Similarly, recessive model (AA vs. GG+GA: p = 0.016; OR = 1.791,
      95% CI = 1.117 to 2.873) also indicated increased TB risk. Whereas, heterozygous
      (GA vs. GG: p = 0.837; OR = 1.028, 95% CI = 0.791 to 1.335) and dominant (AA+GA
      vs. GG: p = 0.222; OR = 1.188, 95% CI = 0.901 to 1.567) models failed to show
      increased risk of developing TB. CONCLUSIONS: This meta-analysis suggests that
      there is a significant association between the CCL5 -403 G>A polymorphism and
      increased risk of TB. However, larger well-designed epidemiological studies with
      stratified case control and biological characterization may be helpful to
      validate this association.

PMID- 24015212
TI  - Revertant fibers in the mdx murine model of Duchenne muscular dystrophy: an age-
      and muscle-related reappraisal.
AB  - Muscles in Duchenne dystrophy patients are characterized by the absence of
      dystrophin, yet transverse sections show a small percentage of fibers (termed
      "revertant fibers") positive for dystrophin expression. This phenomenon, whose
      biological bases have not been fully elucidated, is present also in the murine
      and canine models of DMD and can confound the evaluation of therapeutic
      approaches. We analyzed 11 different muscles in a cohort of 40 mdx mice, the most
      commonly model used in pre-clinical studies, belonging to four age groups; such
      number of animals allowed us to perform solid ANOVA statistical analysis. We
      assessed the average number of dystrophin-positive fibers, both absolute and
      normalized for muscle size, and the correlation between their formation and the
      ageing process. Our results indicate that various muscles develop different
      numbers of revertant fibers, with different time trends; besides, they suggest
      that the biological mechanism(s) behind dystrophin re-expression might not be
      limited to the early development phases but could actually continue during
      adulthood. Importantly, such finding was seen also in cardiac muscle, a fact that
      does not fit into the current hypothesis of the clonal origin of "revertant"
      myonuclei from satellite cells. This work represents the largest, statistically
      significant analysis of revertant fibers in mdx mice so far, which can now be
      used as a reference point for improving the evaluation of therapeutic approaches
      for DMD. At the same time, it provides new clues about the formation of revertant
      fibers/cardiomyocytes in dystrophic skeletal and cardiac muscle. 

PMID- 24015213
TI  - Drug-induced acute myocardial infarction: identifying 'prime suspects' from
      electronic healthcare records-based surveillance system.
AB  - BACKGROUND: Drug-related adverse events remain an important cause of morbidity
      and mortality and impose huge burden on healthcare costs. Routinely collected
      electronic healthcare data give a good snapshot of how drugs are being used in
      'real-world' settings. OBJECTIVE: To describe a strategy that identifies
      potentially drug-induced acute myocardial infarction (AMI) from a large
      international healthcare data network. METHODS: Post-marketing safety
      surveillance was conducted in seven population-based healthcare databases in
      three countries (Denmark, Italy, and the Netherlands) using anonymised
      demographic, clinical, and prescription/dispensing data representing 21,171,291
      individuals with 154,474,063 person-years of follow-up in the period 1996-2010.
      Primary care physicians' medical records and administrative claims containing
      reimbursements for filled prescriptions, laboratory tests, and hospitalisations
      were evaluated using a three-tier triage system of detection, filtering, and
      substantiation that generated a list of drugs potentially associated with AMI.
      Outcome of interest was statistically significant increased risk of AMI during
      drug exposure that has not been previously described in current literature and is
      biologically plausible. RESULTS: Overall, 163 drugs were identified to be
      associated with increased risk of AMI during preliminary screening. Of these, 124
      drugs were eliminated after adjustment for possible bias and confounding. With
      subsequent application of criteria for novelty and biological plausibility,
      association with AMI remained for nine drugs ('prime suspects'): azithromycin;
      erythromycin; roxithromycin; metoclopramide; cisapride; domperidone;
      betamethasone; fluconazole; and megestrol acetate. LIMITATIONS: Although global
      health status, co-morbidities, and time-invariant factors were adjusted for,
      residual confounding cannot be ruled out. CONCLUSION: A strategy to identify
      potentially drug-induced AMI from electronic healthcare data has been proposed
      that takes into account not only statistical association, but also public health
      relevance, novelty, and biological plausibility. Although this strategy needs to
      be further evaluated using other healthcare data sources, the list of 'prime
      suspects' makes a good starting point for further clinical, laboratory, and
      epidemiologic investigation.

PMID- 24015215
TI  - Comparative analysis of induced vs. spontaneous models of autoimmune uveitis
      targeting the interphotoreceptor retinoid binding protein.
AB  - Animal models of autoimmunity to the retina mimic specific features of human
      uveitis, but no model by itself reproduces the full spectrum of human disease. We
      compared three mouse models of uveitis that target the interphotoreceptor
      retinoid binding protein (IRBP): (i) the "classical" model of experimental
      autoimmune uveitis (EAU) induced by immunization with IRBP; (ii) spontaneous
      uveitis in IRBP T cell receptor transgenic mice (R161H) and (iii) spontaneous
      uveitis in Autoimmune Regulator (AIRE)(-/-) mice. Disease course and severity,
      pathology and changes in visual function were studied using fundus imaging and
      histological examinations, optical coherence tomography and electroretinography.
      All models were on the B10.RIII background. Unlike previously reported, IRBP
      induced EAU in B10.RIII mice exhibited two distinct patterns of disease depending
      on clinical scores developed after onset: severe monophasic with extensive
      destruction of the retina and rapid loss of visual signal, or lower grade with a
      prolonged chronic phase culminating after several months in retinal degeneration
      and loss of vision. R161H and AIRE(-/-) mice spontaneously developed chronic
      progressive inflammation; visual function declined gradually as retinal
      degeneration developed. Spontaneous uveitis in R161H mice was characterized by
      persistent cellular infiltrates and lymphoid aggregation, whereas AIRE(-/-) mice
      characteristically developed multi-focal infiltrates and severe choroidal
      inflammation. These data demonstrate variability and unique distinguishing
      features in the different models of uveitis, suggesting that each one can
      represent distinct aspects of uveitis in humans. 

PMID- 24015214
TI  - The soluble guanylate cyclase activator BAY 58-2667 protects against morbidity
      and mortality in endotoxic shock by recoupling organ systems.
AB  - Sepsis and septic shock are associated with high mortality rates and the majority
      of sepsis patients die due to complications of multiple organ failure (MOF). The
      cyclic GMP (cGMP) producing enzyme soluble guanylate cyclase (sGC) is crucially
      involved in the regulation of (micro)vascular homeostasis, cardiac function and,
      consequently, organ function. However, it can become inactivated when exposed to
      reactive oxygen species (ROS). The resulting heme-free sGC can be reactivated by
      the heme- and nitric oxide (NO)-independent sGC activator BAY 58-2667
      (Cinaciguat). We report that late (+8 h) post-treatment with BAY 58-2667 in a
      mouse model can protect against lethal endotoxic shock. Protection was associated
      with reduced hypothermia, circulating IL-6 levels, cardiomyocyte apoptosis, and
      mortality. In contrast to BAY 58-2667, the sGC stimulator BAY 41-2272 and the
      phosphodiesterase 5 inhibitor Sildenafil did not have any beneficial effect on
      survival, emphasizing the importance of the selectivity of BAY 58-2667 for
      diseased vessels and tissues. Hemodynamic parameters (blood pressure and heart
      rate) were decreased, and linear and nonlinear indices of blood pressure
      variability, reflective for (un)coupling of the communication between the
      autonomic nervous system and the heart, were improved after late protective
      treatment with BAY 58-2667. In conclusion, our results demonstrate the pivotal
      role of the NO/sGC axis in endotoxic shock. Stabilization of sGC function with
      BAY 58-2667 can prevent mortality when given in the correct treatment window,
      which probably depends on the dynamics of the heme-free sGC pool, in turn
      influenced by oxidative stress. We speculate that, considering the central role
      of sGC signaling in many pathways required for maintenance of (micro)circulatory
      homeostasis, BAY 58-2667 supports organ function by recoupling inter-organ
      communication pathways. 

PMID- 24015216
TI  - A descriptive analysis of HIV prevalence, HIV service uptake, and HIV-related
      risk behaviour among patients attending a mental health clinic in Rural Malawi.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) and mental illness are interlinked
      health problems; mental illness may pose a risk for contracting HIV and HIV
      positive individuals are at higher risk of mental illness. However, in countries
      with high HIV prevalence, the main focus of HIV-related health programmes is
      usually on prevention and treatment of somatic complications of HIV, and mental
      illness is not given high priority. We examined HIV prevalence, uptake of HIV
      services, and HIV-related risk behaviour among people attending a mental health
      clinic in rural Malawi. METHODOLOGY: Semi-structured interviews were performed
      with patients capable to consent (94%), and with those accompanied by a capable
      caregiver who consented. HIV counselling and testing was offered to participants.
      FINDINGS: Among 174 participants, we collected 162 HIV test results (91%). HIV
      prevalence was 14.8%. Women were three times as likely to be HIV-positive
      compared to men. Two-thirds of participants reported having been tested for HIV
      prior to this study. The uptake of HIV-services among HIV-positive patients was
      low: 35% did not use recommended prophylactic therapy and 44% of patients not
      receiving antiretroviral treatment (ART) had never been assessed for ART
      eligibility. The reported rate of sexual activity was 61%, and 9% of sexually
      active participants had multiple partners. Inconsistent condom use with stable
      (89%) and occasional (79%) sexual partners, and absence of knowledge of the HIV
      status of those partners (53%, 63%) indicate high levels of sexual risk
      behaviour. CONCLUSIONS: HIV-prevalence among persons attending the clinic,
      particularly men, was lower than among the general population in a population
      survey. The rate of HIV testing was high, but there was low uptake of preventive
      measures and ART. This illustrates that HIV-positive individuals with mental
      illness or epilepsy constitute a vulnerable population. HIV programmes should
      include those with neuropsychiatric illness.

PMID- 24015217
TI  - A novel constraint for thermodynamically designing DNA sequences.
AB  - Biotechnological and biomolecular advances have introduced novel uses for DNA
      such as DNA computing, storage, and encryption. For these applications, DNA
      sequence design requires maximal desired (and minimal undesired) hybridizations,
      which are the product of a single new DNA strand from 2 single DNA strands. Here,
      we propose a novel constraint to design DNA sequences based on thermodynamic
      properties. Existing constraints for DNA design are based on the Hamming
      distance, a constraint that does not address the thermodynamic properties of the
      DNA sequence. Using a unique, improved genetic algorithm, we designed DNA
      sequence sets which satisfy different distance constraints and employ a free
      energy gap based on a minimum free energy (MFE) to gauge DNA sequences based on
      set thermodynamic properties. When compared to the best constraints of the
      Hamming distance, our method yielded better thermodynamic qualities. We then used
      our improved genetic algorithm to obtain lower-bound DNA sequence sets. Here, we
      discuss the effects of novel constraint parameters on the free energy gap. 

PMID- 24015218
TI  - Elucidating the signal responses of multi-parametric surface plasmon resonance
      living cell sensing: a comparison between optical modeling and drug-MDCKII cell
      interaction measurements.
AB  - In vitro cell-based assays are widely used during the drug discovery and
      development process to test the biological activity of new drugs. Most of the
      commonly used cell-based assays, however, lack the ability to measure in real
      time or under dynamic conditions (e.g. constant flow). In this study a multi
      parameter surface plasmon resonance approach in combination with living cell
      sensing has been utilized for monitoring drug-cell interactions in real-time,
      under constant flow and without labels. The multi-parameter surface plasmon
      resonance approach, i.e. surface plasmon resonance angle versus intensity plots,
      provided fully specific signal patterns for various cell behaviors when
      stimulating cells with drugs that use para- and transcellular absorption routes.
      Simulated full surface plasmon resonance angular spectra of cell monolayers were
      compared with actual surface plasmon resonance measurements performed with MDCKII
      cell monolayers in order to better understand the origin of the surface plasmon
      resonance signal responses during drug stimulation of cells. The comparison of
      the simulated and measured surface plasmon resonance responses allowed to better
      understand and provide plausible explanations for the type of cellular changes,
      e.g. morphological or mass redistribution in cells, that were induced in the
      MDCKII cell monolayers during drug stimulation, and consequently to differentiate
      between the type and modes of drug actions. The multi-parameter surface plasmon
      resonance approach presented in this study lays the foundation for developing new
      types of cell-based tools for life science research, which should contribute to
      an improved mechanistic understanding of the type and contribution of different
      drug transport routes on drug absorption. 

PMID- 24015219
TI  - Why are product prices in online markets not converging?
AB  - Why are product prices in online markets dispersed in spite of very small search
      costs? To address this question, we construct a unique dataset from a Japanese
      price comparison site, which records price quotes offered by e-retailers as well
      as customers' clicks on products, which occur when they proceed to purchase the
      product. The novelty of our approach is that we seek to extract useful
      information on the source of price dispersion from the shape of price
      distributions rather than focusing merely on the standard deviation or the
      coefficient of variation of prices, as previous studies have done. We find that
      the distribution of prices retailers quote for a particular product at a
      particular point in time (divided by the lowest price) follows an exponential
      distribution, showing the presence of substantial price dispersion. For example,
      20 percent of all retailers quote prices that are more than 50 percent higher
      than the lowest price. Next, comparing the probability that customers click on a
      retailer with a particular rank and the probability that retailers post prices at
      a particular rank, we show that both decline exponentially with price rank and
      that the exponents associated with the probabilities are quite close. This
      suggests that the reason why some retailers set prices at a level substantially
      higher than the lowest price is that they know that some customers will choose
      them even at that high price. Based on these findings, we hypothesize that price
      dispersion in online markets stems from heterogeneity in customers' preferences
      over retailers; that is, customers choose a set of candidate retailers based on
      their preferences, which are heterogeneous across customers, and then pick a
      particular retailer among the candidates based on the price ranking. 

PMID- 24015220
TI  - The effect of differentiation induction on FAK and Src activity in live HMSCs
      visualized by FRET.
AB  - FAK and Src signaling play important roles in cell differentiation, survival and
      migration. However, it remains unclear how FAK and Src activities are regulated
      at the initial stage of stem cell differentiation. We utilized fluorescence
      resonance energy transfer (FRET)-based FAK and Src biosensors to visualize these
      kinase activities at the plasma membrane of human mesenchymal stem cells (HMSCs)
      under the stimulation of osteogenic, myoblastic, or neural induction reagents.
      Our results indicate that the membrane FAK and Src activities are distinctively
      regulated by these differentiation induction reagents. FAK and Src activities
      were both up-regulated with positive feedback upon osteogenic induction, while
      myoblastic induction only activated Src, but not FAK. Neural induction, however,
      transiently activated FAK and subsequently Src, which triggered a negative
      feedback to partially inhibit FAK activity. These results unravel distinct
      regulation mechanisms of FAK and Src activities during HMSC fate decision, which
      should advance our understanding of stem cell differentiation in tissue
      engineering. 

PMID- 24015221
TI  - iGPCR-drug: a web server for predicting interaction between GPCRs and drugs in
      cellular networking.
AB  - Involved in many diseases such as cancer, diabetes, neurodegenerative,
      inflammatory and respiratory disorders, G-protein-coupled receptors (GPCRs) are
      among the most frequent targets of therapeutic drugs. It is time-consuming and
      expensive to determine whether a drug and a GPCR are to interact with each other
      in a cellular network purely by means of experimental techniques. Although some
      computational methods were developed in this regard based on the knowledge of the
      3D (dimensional) structure of protein, unfortunately their usage is quite limited
      because the 3D structures for most GPCRs are still unknown. To overcome the
      situation, a sequence-based classifier, called "iGPCR-drug", was developed to
      predict the interactions between GPCRs and drugs in cellular networking. In the
      predictor, the drug compound is formulated by a 2D (dimensional) fingerprint via
      a 256D vector, GPCR by the PseAAC (pseudo amino acid composition) generated with
      the grey model theory, and the prediction engine is operated by the fuzzy K
      nearest neighbour algorithm. Moreover, a user-friendly web-server for iGPCR-drug
      was established at http://www.jci-bioinfo.cn/iGPCR-Drug/. For the convenience of
      most experimental scientists, a step-by-step guide is provided on how to use the
      web-server to get the desired results without the need to follow the complicated
      math equations presented in this paper just for its integrity. The overall
      success rate achieved by iGPCR-drug via the jackknife test was 85.5%, which is
      remarkably higher than the rate by the existing peer method developed in 2010
      although no web server was ever established for it. It is anticipated that iGPCR
      Drug may become a useful high throughput tool for both basic research and drug
      development, and that the approach presented here can also be extended to study
      other drug - target interaction networks. 

PMID- 24015222
TI  - Characterizing Alzheimer's disease severity via resting-awake EEG amplitude
      modulation analysis.
AB  - Changes in electroencephalography (EEG) amplitude modulations have recently been
      linked with early-stage Alzheimer's disease (AD). Existing tools available to
      perform such analysis (e.g., detrended fluctuation analysis), however, provide
      limited gains in discriminability power over traditional spectral based EEG
      analysis. In this paper, we explore the use of an innovative EEG amplitude
      modulation analysis technique based on spectro-temporal signal processing. More
      specifically, full-band EEG signals are first decomposed into the five well-known
      frequency bands and the envelopes are then extracted via a Hilbert transform.
      Each of the five envelopes are further decomposed into four so-called modulation
      bands, which were chosen to coincide with the delta, theta, alpha and beta
      frequency bands. Experiments on a resting-awake EEG dataset collected from 76
      participants (27 healthy controls, 27 diagnosed with mild-AD, and 22 with
      moderate-AD) showed significant differences in amplitude modulations between the
      three groups. Most notably, i) delta modulation of the beta frequency band
      disappeared with an increase in disease severity (from mild to moderate AD), ii)
      delta modulation of the theta band appeared with an increase in severity, and
      iii) delta modulation of the beta frequency band showed to be a reliable
      discriminant feature between healthy controls and mild-AD patients. Taken
      together, it is hoped that the developed tool can be used to assist clinicians
      not only with early detection of Alzheimer's disease, but also to monitor its
      progression. 

PMID- 24015223
TI  - Perceptions and practices of self-medication among medical students in coastal
      South India.
AB  - Self-medication is a common practice worldwide and the irrational use of drugs is
      a cause of concern. This study assessed the prevalence of self-medication among
      the medical students in South India. The data was analysed using SPSS version
      11.5. A total of 440 students were included in the study. The prevalence of self
      medication was 78.6%. A larger number of females were self-medicating (81.2%)
      than males (75.3%). The majority of the students self-medicated because of the
      illness being too trivial for consultation (70.5%). Antipyretics were most
      commonly self-medicated by the participants (74.8%). Only 47% of the participants
      opined that self-medication was a part of self-care and it needs to be
      encouraged. 39.3% of the participants perceived that the supply of medicine
      without prescription by the pharmacist can prevent the growing trend of self
      medication. Easy availability and accessibility to health care facilities remains
      the cornerstone for reducing the practice of self-medication. 

PMID- 24015224
TI  - IFN-gamma-stimulated neutrophils suppress lymphocyte proliferation through
      expression of PD-L1.
AB  - During systemic inflammation different neutrophil subsets are mobilized to the
      peripheral blood. These neutrophil subsets can be distinguished from normal
      circulating neutrophils (CD16(bright)/CD62L(bright)), based on either an immature
      CD16(dim)/CD62L(bright) or a CD16(bright)/CD62L(dim) phenotype. Interestingly,
      the latter neutrophil subset is known to suppress lymphocyte proliferation ex
      vivo, but how neutrophils become suppressive is unknown. We performed
      transcriptome analysis on the different neutrophil subsets to identify changes in
      mRNA expression that are relevant for their functions. Neutrophil subsets were
      isolated by fluorescence-activated cell sorting from blood of healthy volunteers
      that were administered a single dose of lipopolysaccharide (2 ng/kg i.v.) and the
      transcriptome was determined by microarray analysis. Interestingly, the
      CD16(bright)/CD62L(dim) suppressive neutrophils showed an interferon-induced
      transcriptome profile. More importantly, IFN-gamma, but not IFN-alpha or IFN-beta
      stimulated neutrophils, acquired the capacity to suppress lymphocyte
      proliferation through the expression of programmed death ligand 1 (PD-L1). These
      data demonstrate that IFN-gamma-induced expression of PD-L1 on neutrophils
      enables suppression of lymphocyte proliferation. Specific stimulation of
      neutrophils present at the inflammatory sites might therefore have a pivotal role
      in regulating lymphocyte-mediated inflammation and autoimmune disease. 

PMID- 24015225
TI  - Indirect estimation of the comparative treatment effect in pharmacogenomic
      subgroups.
AB  - Evidence of clinical utility is a key issue in translating pharmacogenomics into
      clinical practice. Appropriately designed randomized controlled trials generally
      provide the most robust evidence of the clinical utility, but often only data
      from a pharmacogenomic association study are available. This paper details a
      method for reframing the results of pharmacogenomic association studies in terms
      of the comparative treatment effect for a pharmacogenomic subgroup to provide
      greater insight into the likely clinical utility of a pharmacogenomic marker,
      its' likely cost effectiveness, and the value of undertaking the further (often
      expensive) research required for translation into clinical practice. The method
      is based on the law of total probability, which relates marginal and conditional
      probability. It takes as inputs: the prevalence of the pharmacogenomic marker in
      the patient group of interest, prognostic effect of the pharmacogenomic marker
      based on observational association studies, and the unstratified comparative
      treatment effect based on one or more conventional randomized controlled trials.
      The critical assumption is that of exchangeability across the included studies.
      The method is demonstrated using a case study of cytochrome P450 (CYP) 2C19
      genotype and the anti-platelet agent clopidogrel. Indirect subgroup analysis
      provided insight into relationship between the clinical utility of genotyping
      CYP2C19 and the risk ratio of cardiovascular outcomes between CYP2C19 genotypes
      for individuals using clopidogrel. In this case study the indirect and direct
      estimates of the treatment effect for the cytochrome P450 2C19 subgroups were
      similar. In general, however, indirect estimates are likely to have substantially
      greater risk of bias than an equivalent direct estimate. 

PMID- 24015226
TI  - Self-fulfilling prophecies as a link between men's facial width-to-height ratio
      and behavior.
AB  - The facial width-to-height ratio (fWHR) has been identified as a reliable
      predictor of men's behavior, with researchers focusing on evolutionary selection
      pressures as the underlying mechanism explaining these relationships. In this
      paper, we complement this approach and examine the extent to which social
      processes also determine the extent to which men's fWHR serves as a behavioral
      cue. Specifically, we propose that observers' treatment of target men based on
      the targets' fWHR subsequently affects behavior, leading the targets to behave in
      ways that are consistent with the observers' expectations (i.e., a self
      fulfilling prophecy). Results from four studies demonstrate that individuals
      behave more selfishly when interacting with men with greater fWHRs, and this
      selfish behavior, in turn, elicits selfish behavior in others. 

PMID- 24015227
TI  - In vitro formation of beta cell pseudoislets using islet-derived endothelial
      cells.
AB  - beta cell pseudoislets (PIs) are used for the in vitro study of beta-cells in a
      three-dimensional (3-D) configuration. Current methods of PI induction require
      unique culture conditions and extensive mechanical manipulations. Here we report
      a novel co-culture system consisting of high passage beta-cells and islet-derived
      endothelial cells (iECs) that results in a rapid and spontaneous formation of
      free-floating PIs. PI structures were formed as early as 72 h following co
      culture setup and were preserved for more than 14 d. These PIs, composed solely
      of beta-cells, were similar in size to that of native islets and showed an
      increased percentage of proinsulin-positive cells, increased insulin gene
      expression in response to glucose stimulation, and restored glucose-stimulated
      insulin secretion when compared to beta-cells cultured as monolayers. Key
      extracellular matrix proteins that were absent in beta-cells cultured alone were
      deposited by iECs on PIs and were found in and around the PIs. iEC-induced PIs
      are a readily available tool for examining beta cell function in a native 3-D
      configuration and can be used for examining beta-cell/iEC interactions in vitro. 

PMID- 24015229
TI  - A reassessment of Bergmann's rule in modern humans.
AB  - It is widely accepted that modern humans conform to Bergmann's rule, which holds
      that body size in endothermic species will increase as temperature decreases.
      However, there are reasons to question the reliability of the findings on which
      this consensus is based. One of these is that the main studies that have reported
      that modern humans conform to Bergmann's rule have employed samples that contain
      a disproportionately large number of warm-climate and northern hemisphere groups.
      With this in mind, we used latitudinally-stratified and hemisphere-specific
      samples to re-assess the relationship between modern human body size and
      temperature. We found that when groups from north and south of the equator were
      analyzed together, Bergmann's rule was supported. However, when groups were
      separated by hemisphere, Bergmann's rule was only supported in the northern
      hemisphere. In the course of exploring these results further, we found that the
      difference between our northern and southern hemisphere subsamples is due to the
      limited latitudinal and temperature range in the latter subsample. Thus, our
      study suggests that modern humans do conform to Bergmann's rule but only when
      there are major differences in latitude and temperature among groups.
      Specifically, groups must span more than 50 degrees of latitude and/or more than
      30 degrees C for it to hold. This finding has important implications for work on
      regional variation in human body size and its relationship to temperature. 

PMID- 24015228
TI  - Autophagy enhances bacterial clearance during P. aeruginosa lung infection.
AB  - Pseudomonas aeruginosa is an opportunistic bacterial pathogen which is the
      leading cause of morbidity and mortality among cystic fibrosis patients. Although
      P. aeruginosa is primarily considered an extacellular pathogen, recent reports
      have demonstrated that throughout the course of infection the bacterium acquires
      the ability to enter and reside within host cells. Normally intracellular
      pathogens are cleared through a process called autophagy which sequesters and
      degrades portions of the cytosol, including invading bacteria. However the role
      of autophagy in host defense against P. aeruginosa in vivo remains unknown.
      Understanding the role of autophagy during P. aeruginosa infection is of
      particular importance as mutations leading to cystic fibrosis have recently been
      shown to cause a blockade in the autophagy pathway, which could increase
      susceptibility to infection. Here we demonstrate that P. aeruginosa induces
      autophagy in mast cells, which have been recognized as sentinels in the host
      defense against bacterial infection. We further demonstrate that inhibition of
      autophagy through pharmacological means or protein knockdown inhibits clearance
      of intracellular P. aeruginosa in vitro, while pharmacologic induction of
      autophagy significantly increased bacterial clearance. Finally we find that
      pharmacological manipulation of autophagy in vivo effectively regulates bacterial
      clearance of P. aeruginosa from the lung. Together our results demonstrate that
      autophagy is required for an effective immune response against P. aeruginosa
      infection in vivo, and suggest that pharmacological interventions targeting the
      autophagy pathway could have considerable therapeutic potential in the treatment
      of P. aeruginosa lung infection. 

PMID- 24015230
TI  - Genetic background may contribute to PAM50 gene expression breast cancer subtype
      assignments.
AB  - Recent advances in genome wide transcriptional analysis have provided greater
      insights into the etiology and heterogeneity of breast cancer. Molecular
      signatures have been developed that stratify the conventional estrogen receptor
      positive or negative categories into subtypes that are associated with differing
      clinical outcomes. It is thought that the expression patterns of the molecular
      subtypes primarily reflect cell-of-origin or tumor driver mutations. In this
      study however, using a genetically engineered mouse mammary tumor model we
      demonstrate that the PAM50 subtype signature of tumors driven by a common
      oncogenic event can be significantly influenced by the genetic background on
      which the tumor arises. These results have important implications for
      interpretation of "snapshot" expression profiles, as well as suggesting that
      incorporation of genetic background effects may allow investigation into
      phenotypes not initially anticipated in individual mouse models of cancer. 

PMID- 24015231
TI  - The RNA binding protein ESRP1 fine-tunes the expression of pluripotency-related
      factors in mouse embryonic stem cells.
AB  - In pluripotent stem cells, there is increasing evidence for crosstalk between
      post-transcriptional and transcriptional networks, offering multifold steps at
      which pluripotency can be controlled. In addition to well-studied transcription
      factors, chromatin modifiers and miRNAs, RNA-binding proteins are emerging as
      fundamental players in pluripotency regulation. Here, we report a new role for
      the RNA-binding protein ESRP1 in the control of pluripotency. Knockdown of Esrp1
      in mouse embryonic stem cells induces, other than the well-documented epithelial
      to mesenchymal-like state, also an increase in expression of the core
      transcription factors Oct4, Nanog and Sox2, thereby enhancing self-renewal of
      these cells. Esrp1-depleted embryonic stem cells displayed impaired early
      differentiation in vitro and formed larger teratomas in vivo when compared to
      control embryonic stem cells. We also show that ESRP1 binds to Oct4 and Sox2
      mRNAs and decreases their polysomal loading. ESRP1 thus acts as a physiological
      regulator of the finely-tuned balance between self-renewal and commitment to a
      restricted developmental fate. Importantly, both mouse and human epithelial stem
      cells highly express ESRP1, pinpointing the importance of this RNA-binding
      protein in stem cell biology. 

PMID- 24015232
TI  - Use of liver stiffness measurement for liver resection surgery: correlation with
      indocyanine green clearance testing and post-operative outcome.
AB  - BACKGROUND: Liver stiffness measurement (LSM) using transient elastography has
      recently become available for the assessment of liver fibrosis. Whether LSM can
      predict the functional liver reserve in patients undergoing liver resection is
      not certain. AIM: To correlate liver stiffness measurement (LSM) with indocyanine
      green (ICG) clearance test and liver biochemistry, and to determine its
      usefulness in predicting postoperative outcomes in patients undergoing liver
      resection. PATIENTS AND METHODS: Transient elastography and ICG clearance test
      were performed pre-operatively in 44 patients with hepatocellular carcinoma. The
      LSM and ICG retention rate at 15 minutes (R15) were correlated with pre-operative
      factors and post-operative outcomes. RESULTS: There was significant correlation
      between ICG R15 and LSM. In patients with LSM >=11 kPa vs <11 kPa, there was
      significantly higher ICG R15 (17.1% vs 10.0% respectively, p = 0.025). For
      patients with ICG R15>=10% compared to those <10%, there was significantly higher
      LSM (12.0 vs 7.6 kPa respectively, p = 0.015). Twenty-eight patients proceeded to
      resection. There was a significant correlation between LSM and the peak INR after
      liver resection (r = 0.426, p = 0.024). There was a significant correlation
      between ICG R15 and the post-operative peak AST level (r = -0.414, p = 0.029) and
      peak ALT level (r = -0.568, p = 0.002). The operative time was a significant
      independent factor associated with post-operative complications and peak INR.
      CONCLUSION: LSM correlated well with ICG R15 in patients undergoing liver
      resection, and predicted early post-operative complications. Addition of LSM to
      ICG R15 testing may provide better prognostic information for patients undergoing
      resection.

PMID- 24015233
TI  - Two invaders instead of one: the true identity of species under the name Ceracis
      cucullatus (Coleoptera: Ciidae).
AB  - The Neotropical obligate fungivorous beetle Ceracis cucullatus (Mellie) has
      attracted attention of coleopterists due to the increasing number of records of
      populations in Africa. Although its disjunct populations have been interpreted as
      a cohesive taxonomic unity, previous comparisons between African and Neotropical
      specimens revealed differences in their external morphology, causing uncertainty
      about the true unity of the species. Here, we compare the external morphology of
      specimens named Cer. cucullatus from several localities of the Neotropical,
      Palearctic, Afrotropical, Afrotemperate and Oriental regions. As results, we
      reverse three previous junior synonymies of Cer. cucullatus, proposing Cer.
      lamellatus (Pic) and Cer. tabellifer (Mellie), both reinstated status and new
      combinations, as separate species. We also propose Enn. bilamellatum Pic as a new
      synonym of Cer. tabellifer. In face of these taxonomic changes, we identify Cer.
      tabellifer as the actual invasive species on African lands, instead of Cer.
      cucullatus as was previously accepted. Then, through historical records gathered
      from scientific collections and literature, and through examination of recently
      collected specimens from South Africa and Brazil, we provide data on host fungi
      and geographic distribution of Cer. tabellifer. Based on these data, we discuss
      possible explanations to the successful invasion of Cer. tabellifer in Africa and
      elsewhere and its potential threat to native faunas of ciids. This study helps to
      fulfil an old gap in the literature on biological invasions, with considerably
      more studies on predatory species, disease vectors or potential pests of
      agricultural crops, than on non-pest fungivorous organisms. 

PMID- 24015234
TI  - Quantitative reconstruction of weaning ages in archaeological human populations
      using bone collagen nitrogen isotope ratios and approximate Bayesian computation.
AB  - BACKGROUND: Nitrogen isotope analysis of bone collagen has been used to
      reconstruct the breastfeeding practices of archaeological human populations.
      However, weaning ages have been estimated subjectively because of a lack of both
      information on subadult bone collagen turnover rates and appropriate analytical
      models. METHODOLOGY: Temporal changes in human subadult bone collagen turnover
      rates were estimated from data on tissue-level bone metabolism reported in
      previous studies. A model for reconstructing precise weaning ages was then
      developed using a framework of approximate Bayesian computation and incorporating
      the estimated turnover rates. The model is presented as a new open source R
      package, WARN (Weaning Age Reconstruction with Nitrogen isotope analysis), which
      computes the age at the start and end of weaning, (15)N-enrichment through
      maternal to infant tissue, and [Formula: see text] value of collagen synthesized
      entirely from weaning foods with their posterior probabilities. The model was
      applied to 39 previously reported Holocene skeletal populations from around the
      world, and the results were compared with weaning ages observed in ethnographic
      studies. CONCLUSIONS: There were no significant differences in the age at the end
      of weaning between the archaeological (2.80+/-1.32 years) and ethnographic
      populations. By comparing archaeological populations, it appears that weaning
      ages did not differ with the type of subsistence practiced (i.e., hunting
      gathering or not). Most of [Formula: see text]-enrichment (2.44+/-0.900/00) was
      consistent with biologically valid values. The nitrogen isotope ratios of
      subadults after the weaning process were lower than those of adults in most of
      the archaeological populations (-0.48+/-0.610/00), and this depletion was greater
      in non-hunter-gatherer populations. Our results suggest that the breastfeeding
      period in humans had already been shortened by the early Holocene compared with
      those in extant great apes.

PMID- 24015235
TI  - Interleukin 6 deficiency modulates the hypothalamic expression of energy balance
      regulating peptides during pregnancy in mice.
AB  - Pregnancy is associated with hyperphagia, increased adiposity and multiple
      neuroendocrine adaptations. Maternal adipose tissue secretes rising amounts of
      interleukin 6 (IL6), which acts peripherally modulating metabolic function and
      centrally increasing energy expenditure and reducing body fat. To explore the
      role of IL6 in the central mechanisms governing dam's energy homeostasis, early,
      mid and late pregnant (gestational days 7, 13 and 18) wild-type (WT) and Il6
      knockout mice (Il6-KO) were compared with virgin controls at diestrus. Food
      intake, body weight and composition as well as indirect calorimetry measurements
      were performed in vivo. Anabolic and orexigenic peptides: neuropeptide Y (Npy)
      and agouti-related peptide (Agrp); and catabolic and anorectic neuropeptides:
      proopiomelanocortin (Pomc), corticotrophin and thyrotropin-releasing hormone (Crh
      and Trh) mRNA levels were determined by in situ hybridization. Real time-PCR and
      western-blot were used for additional tissue gene expression and protein studies.
      Non-pregnant Il6-KO mice were leaner than WT mice due to a decrease in fat but
      not in lean body mass. Pregnant Il6-KO mice had higher fat accretion despite
      similar body weight gain than WT controls. A decreased fat utilization in absence
      of Il6 might explain this effect, as shown by increased respiratory exchange
      ratio (RER) in virgin Il6-KO mice. Il6 mRNA levels were markedly enhanced in
      adipose tissue but reduced in hypothalamus of mid and late pregnant WT mice. Trh
      expression was also stimulated at gestational day 13 and lack of Il6 blunted this
      effect. Conversely, in late pregnant mice lessened hypothalamic Il6 receptor
      alpha (Il6ra), Pomc and Crh mRNA were observed. Il6 deficiency during this stage
      up-regulated Npy and Agrp expression, while restoring Pomc mRNA levels to virgin
      values. Together these results demonstrate that IL6/IL6Ra system modulates
      Npy/Agrp, Pomc and Trh expression during mouse pregnancy, supporting a role of
      IL6 in the central regulation of body fat in this physiological state. 

PMID- 24015236
TI  - Gelam honey attenuates carrageenan-induced rat paw inflammation via NF-kappaB
      pathway.
AB  - The activation of nuclear factor kappa B (NF-kappaB) plays a major role in the
      pathogenesis of a number of inflammatory diseases. In this study, we investigated
      the anti-inflammatory mechanism of Gelam honey in inflammation induced rats via
      NF-kappaB signalling pathway. Rats paw edema was induced by subplantar injection
      of 1% carrageenan into the right hind paw. Rats were pre-treated with Gelam honey
      at different doses (1 or 2 g/kg, p.o.) and NSAID Indomethacin (10 mg/kg, p.o.),
      in two time points (1 and 7 days). Our results showed that Gelam honey at both
      concentrations suppressed the gene expressions of NF-kappaB (p65 & p50) and
      IkappaBalpha in inflamed rats paw tissues. In addition, Gelam honey inhibited the
      nuclear translocation and activation of NF-kappaB and decreased the cytosolic
      degradation of IkappaBalpha dose dependently in inflamed rats paw tissues. The
      immunohistochemical expressions of pro-inflammatory mediators COX-2 and TNF-alpha
      were also decreased in inflamed rats paw tissues when treated with Gelam honey.
      The results of our findings suggest that Gelam honey exhibits its inhibitory
      effects by attenuating NF-kappaB translocation to the nucleus and inhibiting
      IkappaBalpha degradation, with subsequent decrease of inflammatory mediators COX
      2 and TNF-alpha. 

PMID- 24015237
TI  - Modelling of usual nutrient intakes: potential impact of the choices programme on
      nutrient intakes in young dutch adults.
AB  - INTRODUCTION: The Choices Programme is an internationally applicable nutrient
      profiling system with nutrition criteria for trans fatty acids (TFA), saturated
      fatty acids, sodium, added sugar and for some product groups energy and fibre.
      These criteria determine whether foods are eligible to carry a "healthier option"
      stamp. In this paper a nutrient intake modelling method is described to evaluate
      these nutritional criteria by investigating the potential effect on nutrient
      intakes. METHODS: Data were combined from the 2003 Dutch food consumption survey
      in young adults (aged 19-30) and the Dutch food composition table into the Monte
      Carlo Risk Assessment model. Three scenarios were calculated: the "actual
      intakes" (scenario 1) were compared to scenario 2, where all foods that did not
      comply were replaced by similar foods that did comply with the Choices criteria.
      Scenario 3 was the same as scenario 2 adjusted for the difference in energy
      density between the original and replacement food. Additional scenarios were
      calculated where snacks were not or partially replaced and stratified analyses
      for gender, age, Body Mass Index (BMI) and education. RESULTS: Calculated intake
      distributions showed that median energy intake was reduced by 16% by replacing
      normally consumed foods with Choices compliant foods. Intakes of nutrients with a
      maximal intake limit were also reduced (ranging from -23% for sodium and -62% for
      TFA). Effects on intakes of beneficial nutrients varied from an unintentional
      reduction in fat soluble vitamin intakes (-15 to -28%) to an increase of 28% for
      fibre and 17% calcium. Stratified analyses in this homogeneous study population
      showed only small differences across gender, age, BMI and education. CONCLUSIONS:
      This intake modelling method showed that with consumption of Choices compliant
      foods, nutrient intakes shift towards population intake goals for the nutrients
      for which nutrition criteria were defined, while effects on beneficial nutrients
      were diverse.

PMID- 24015238
TI  - Are there gender differences in coronary artery disease? The Malaysian National
      Cardiovascular Disease Database - Percutaneous Coronary Intervention (NCVD-PCI)
      Registry.
AB  - OBJECTIVES: To assess whether gender differences exist in the clinical
      presentation, angiographic severity, management and outcomes in patients with
      coronary artery disease (CAD). METHODS: The study comprised of 1,961 women and
      8,593 men who underwent percutaneous coronary intervention (PCI) and were
      included in the Malaysian NCVD-PCI Registry from 2007-2009. Significant stenosis
      was defined as >=70% stenosis in at least one of the epicardial vessels. RESULTS:
      Women were significantly older and had significantly higher rates of diabetes
      mellitus, hypertension, chronic renal failure, new onset angina and prior history
      of heart failure whereas smokers and past history of myocardial infarction were
      higher in men. In the ST-elevation myocardial infarction (STEMI) cohort, more
      women were in Killip class III-IV, had longer door-to-balloon time (169.5 min. vs
      127.3 min, p<0.052) and significantly longer transfer time (300.4 min vs 166.3
      min, p<0.039). Overall, women had significantly more left main stem (LMS) disease
      (1.3% vs 0.6%, p<0.003) and smaller diameter vessels (<3.0 mm: 45.5% vs 34.8%,
      p<0.001). In-hospital mortality rates for all PCI, STEMI, Non-STEMI (NSTEMI) and
      unstable angina for women and men were 1.99% vs 0.98%, Odds ratio (OR): 2.06 (95%
      confidence interval (CI): 1.40 to 3.01), 6.19% vs 2.88%, OR: 2.23 (95% CI: 1.31
      to 3.79), 2.90% vs 0.79%, OR: 3.75 (95% CI: 1.58 to 8.90) and 1.79% vs 0.29%, OR:
      6.18 (95% CI: 0.56 to 68.83), respectively. Six-month adjusted OR for mortality
      for all PCI, STEMI and NSTEMI in women were 2.18 (95% CI: 0.97 to 4.90), 2.68
      (95% CI: 0.37 to 19.61) and 2.66 (95% CI: 0.73 to 9.69), respectively.
      CONCLUSIONS: Women who underwent PCI were older with more co-morbidities. In
      hospital and six-month mortality for all PCI, STEMI and NSTEMI were higher due
      largely to significantly more LMS disease, smaller diameter vessels, longer door
      to-balloon and transfer time in women.

PMID- 24015239
TI  - Fluid dynamics of coarctation of the aorta and effect of bicuspid aortic valve.
AB  - Up to 80% of patients with coarctation of the aorta (COA) have a bicuspid aortic
      valve (BAV). Patients with COA and BAV have elevated risks of aortic
      complications despite successful surgical repair. The development of such
      complications involves the interplay between the mechanical forces applied on the
      artery and the biological processes occurring at the cellular level. The focus of
      this study is on hemodynamic modifications induced in the aorta in the presence
      of a COA and a BAV. For this purpose, numerical investigations and magnetic
      resonance imaging measurements were conducted with different configurations: (1)
      normal: normal aorta and normal aortic valve; (2) isolated COA: aorta with COA
      (75% reduction by area) and normal aortic valve; (3) complex COA: aorta with the
      same severity of COA (75% reduction by area) and BAV. The results show that the
      coexistence of COA and BAV significantly alters blood flow in the aorta with a
      significant increase in the maximal velocity, secondary flow, pressure loss, time
      averaged wall shear stress and oscillatory shear index downstream of the COA.
      These findings can contribute to a better understanding of why patients with
      complex COA have adverse outcome even following a successful surgery. 

PMID- 24015240
TI  - Cerebrospinal fluid interleukin-6 in central nervous system inflammatory
      diseases.
AB  - BACKGROUND: Interleukin (IL)-6 is recognised as an important cytokine involved in
      inflammatory diseases of the central nervous system (CNS). OBJECTIVE: To perform
      a large retrospective study designed to test cerebrospinal fluid (CSF) IL-6
      levels in the context of neurological diseases, and evaluate its usefulness as a
      biomarker to help discriminate multiple sclerosis (MS) from other inflammatory
      neurological diseases (OIND). PATIENTS AND METHODS: We analyzed 374 CSF samples
      for IL-6 using a quantitative enzyme-linked immunosorbent assay. Groups tested
      were composed of demyelinating diseases of the CNS (DD, n = 117), including
      relapsing-remitting MS (RRMS, n = 65), primary progressive MS (PPMS, n = 11),
      clinically isolated syndrome (CIS, n = 11), optic neuritis (ON, n = 30);
      idiopathic transverse myelitis (ITM, n = 10); other inflammatory neurological
      diseases (OIND, n = 35); and non-inflammatory neurological diseases (NIND, n =
      212). Differences between groups were analysed using Kruskal-Wallis test and Mann
      Whitney U-test. RESULTS: CSF IL-6 levels exceeded the positivity cut-off of 10
      pg/ml in 18 (51.4%) of the 35 OIND samples, but in only three (3.9%) of the 76 MS
      samples collected. CSF IL-6 was negative for all NIND samples tested (0/212). IL
      6 cut-off of 10 pg/ml offers 96% sensitivity to exclude MS. CONCLUSION: CSF IL-6
      may help to differentiate MS from its major differential diagnosis group, OIND.

PMID- 24015241
TI  - Enhanced activation of motor execution networks using action observation combined
      with imagination of lower limb movements.
AB  - The combination of first-person observation and motor imagery, i.e. first-person
      observation of limbs with online motor imagination, is commonly used in
      interactive 3D computer gaming and in some movie scenes. These scenarios are
      designed to induce a cognitive process in which a subject imagines
      himself/herself acting as the agent in the displayed movement situation. Despite
      the ubiquity of this type of interaction and its therapeutic potential, its
      relationship to passive observation and imitation during observation has not been
      directly studied using an interactive paradigm. In the present study we show
      activation resulting from observation, coupled with online imagination and with
      online imitation of a goal-directed lower limb movement using functional MRI
      (fMRI) in a mixed block/event-related design. Healthy volunteers viewed a video
      (first-person perspective) of a foot kicking a ball. They were instructed to
      observe-only the action (O), observe and simultaneously imagine performing the
      action (O-MI), or imitate the action (O-IMIT). We found that when O-MI was
      compared to O, activation was enhanced in the ventralpremotor cortex bilaterally,
      left inferior parietal lobule and left insula. The O-MI and O-IMIT conditions
      shared many activation foci in motor relevant areas as confirmed by conjunction
      analysis. These results show that (i) combining observation with motor imagery (O
      MI) enhances activation compared to observation-only (O) in the relevant foot
      motor network and in regions responsible for attention, for control of goal
      directed movements and for the awareness of causing an action, and (ii) it is
      possible to extensively activate the motor execution network using O-MI, even in
      the absence of overt movement. Our results may have implications for the
      development of novel virtual reality interactions for neurorehabilitation
      interventions and other applications involving training of motor tasks. 

PMID- 24015242
TI  - De novo assembly of the Indo-Pacific humpback dolphin leucocyte transcriptome to
      identify putative genes involved in the aquatic adaptation and immune response.
AB  - BACKGROUND: The Indo-Pacific humpback dolphin (Sousa chinensis), a marine mammal
      species inhabited in the waters of Southeast Asia, South Africa and Australia,
      has attracted much attention because of the dramatic decline in population size
      in the past decades, which raises the concern of extinction. So far, this species
      is poorly characterized at molecular level due to little sequence information
      available in public databases. Recent advances in large-scale RNA sequencing
      provide an efficient approach to generate abundant sequences for functional
      genomic analyses in the species with un-sequenced genomes. PRINCIPAL FINDINGS: We
      performed a de novo assembly of the Indo-Pacific humpback dolphin leucocyte
      transcriptome by Illumina sequencing. 108,751 high quality sequences from
      47,840,388 paired-end reads were generated, and 48,868 and 46,587 unigenes were
      functionally annotated by BLAST search against the NCBI non-redundant and Swiss
      Prot protein databases (E-value<10(-5)), respectively. In total, 16,467 unigenes
      were clustered into 25 functional categories by searching against the COG
      database, and BLAST2GO search assigned 37,976 unigenes to 61 GO terms. In
      addition, 36,345 unigenes were grouped into 258 KEGG pathways. We also identified
      9,906 simple sequence repeats and 3,681 putative single nucleotide polymorphisms
      as potential molecular markers in our assembled sequences. A large number of
      unigenes were predicted to be involved in immune response, and many genes were
      predicted to be relevant to adaptive evolution and cetacean-specific traits.
      CONCLUSION: This study represented the first transcriptome analysis of the Indo
      Pacific humpback dolphin, an endangered species. The de novo transcriptome
      analysis of the unique transcripts will provide valuable sequence information for
      discovery of new genes, characterization of gene expression, investigation of
      various pathways and adaptive evolution, as well as identification of genetic
      markers.

PMID- 24015243
TI  - Chaihu-Shugan-San administration ameliorates perimenopausal anxiety and
      depression in rats.
AB  - Chaihu-Shugan-San (CSS) is a traditional Chinese herbal formula that is widely
      used for treating perimenopausal symptoms in China; however, its mechanisms
      remain unknown. The present study was designed to investigate potential CSS
      mechanisms in rats with unpredicted chronic mild stress (UCMS) and normally aging
      rats (52 weeks of age). We performed the sucrose consumption test along with the
      forced swimming test to confirm depression-like behavior and the open field test
      (OFT) to confirm anxiety-like behavior in the animals. In addition, we used an
      enzyme-linked immunosorbent assay to measure serum and hippocampal estradiol (E2)
      levels and a quantitative real-time polymerase chain reaction to assess
      hippocampal mRNA levels of estrogen receptors (ERs) alpha and beta as well as G
      protein-coupled receptor 30 (GPR30). We found that CSS administration resulted in
      a significant increase in the ratio of hippocampal ERalpha and ERbeta mRNA
      (ERalpha/ERbeta ratio) in UCMS rats (p<0.001). However, no significant changes
      were observed in E2 levels, ERalpha mRNA expression, and GPR30 mRNA expression.
      In contrast, changes in ERalpha/ERbeta mRNA ratio were sensitively associated
      with changes in mood states in the animal models. These findings suggest that
      enhancement of ERalpha/ERbeta ratio may play a role in the pharmacological
      mechanisms of CSS. Furthermore, this ratio can be employed as a potential index
      for evaluating mood states in animal models and can be considered as a
      therapeutic target for perimenopausal anxiety and depression in the future. 

PMID- 24015244
TI  - CD49f(high) cells retain sphere-forming and tumor-initiating activities in human
      gastric tumors.
AB  - Identification of gastric tumor-initiating cells (TICs) is essential to explore
      new therapies for gastric cancer patients. There are reports that gastric TICs
      can be identified using the cell surface marker CD44 and that they form floating
      spheres in culture, but we could not obtain consistent results with our patient
      derived tumor xenograft (PDTX) cells. We thus searched for another marker for
      gastric TICs, and found that CD49f(high) cells from newly-dissected gastric
      cancers formed tumors with histological features of parental ones while
      CD49f(low) cells did not when subcutaneously injected into immunodeficient mice.
      These results indicate that CD49f, a subunit of laminin receptors, is a promising
      marker for human gastric TICs. We established a primary culture system for PDTX
      cells where only CD49f(high) cells could grow on extracellular matrix (ECM) to
      form ECM-attaching spheres. When injected into immunodeficient mice, these
      CD49f(high) sphere cells formed tumors with histological features of parental
      ones, indicating that only TICs could grow in the culture system. Using this
      system, we found that some sphere-forming TICs were more resistant than gastric
      tumor cell lines to chemotherapeutic agents, including doxorubicin, 5
      fluorouracil and doxifluridine. There was a patient-dependent difference in the
      tumorigenicity of sphere-forming TICs and their response to anti-tumor drugs.
      These results suggest that ECM plays an essential role for the growth of TICs,
      and that this culture system will be useful to find new drugs targeting gastric
      TICs. 

PMID- 24015245
TI  - Uptake, outcomes, and costs of antenatal, well-baby, and prevention of mother-to
      child transmission of HIV services under routine care conditions in Zambia.
AB  - BACKGROUND: Zambia adopted Option A for prevention of mother-to-child
      transmission of HIV (PMTCT) in 2010 and announced a move to Option B+ in 2013. We
      evaluated the uptake, outcomes, and costs of antenatal, well-baby, and PMTCT
      services under routine care conditions in Zambia after the adoption of Option A.
      METHODS: We enrolled 99 HIV-infected/HIV-exposed (index) mother/baby pairs with a
      first antenatal visit in April-September 2011 at four study sites and 99 HIV
      uninfected/HIV-unexposed (comparison) mother/baby pairs matched on site,
      gestational age, and calendar month at first visit. Data on patient outcomes and
      resources utilized from the first antenatal visit through six months postpartum
      were extracted from site registers. Costs in 2011 USD were estimated from the
      provider's perspective. RESULTS: Index mothers presented for antenatal care at a
      mean 23.6 weeks gestation; 55% were considered to have initiated triple-drug
      antiretroviral therapy (ART) based on information recorded in site registers. Six
      months postpartum, 62% of index and 30% of comparison mother/baby pairs were
      retained in care; 67% of index babies retained had an unknown HIV status.
      Comparison and index mother/baby pairs utilized fewer resources than under fully
      guideline-concordant care; index babies utilized more well-baby resources than
      comparison babies. The average cost per comparison pair retained in care six
      months postpartum was $52 for antenatal and well-baby services. The average cost
      per index pair retained was $88 for antenatal, well-baby, and PMTCT services and
      increased to $185 when costs of triple-drug ART services were included.
      CONCLUSIONS: HIV-infected mothers present to care late in pregnancy and many are
      lost to follow up by six months postpartum. HIV-exposed babies are more likely to
      remain in care and receive non-HIV, well-baby care than HIV-unexposed babies.
      Improving retention in care, guideline concordance, and moving to Option B+ will
      result in increased service delivery costs in the short term.

PMID- 24015246
TI  - Convenient, rapid and accurate measurement of SVOC emission characteristics in
      experimental chambers.
AB  - Chamber tests are usually used to determine the source characteristics of semi
      volatile organic compounds (SVOCs) which are critical to quantify indoor exposure
      to SVOCs. In contrast to volatile organic compounds (VOCs), the sorption effect
      of SVOCs to chamber surfaces usually needs to be considered due to the much
      higher surface/air partition coefficients, resulting in a long time to reach
      steady state, frequently on the order of months, and complicating the
      mathematical analysis of the resulting data. A chamber test is also complicated
      if the material-phase concentration is not constant. This study shows how to
      design a chamber to overcome these limitations. A dimensionless mass transfer
      analysis is used to specify conditions for (1) neglecting the SVOC sorption
      effect to chamber surfaces, (2) neglecting the convective mass transfer
      resistance at sorption surfaces if the sorption effect cannot be neglected, and
      (3) regarding the material-phase concentration in the source as constant. Several
      practical and quantifiable ways to improve chamber design are proposed. The
      approach is illustrated by analyzing available data from three different chambers
      in terms of the accuracy with which the model parameters can be determined and
      the time needed to conduct the chamber test. The results should greatly
      facilitate the design of chambers to characterize SVOC emissions and the
      resulting exposure. 

PMID- 24015247
TI  - Perceived stress at work is associated with lower levels of DHEA-S.
AB  - BACKGROUND: It is known that long-term psychosocial stress may cause or
      contribute to different diseases and symptoms and accelerate aging. One of the
      consequences of prolonged psychosocial stress may be a negative effect on the
      levels of dehydroepiandrosterone (DHEA) and its sulphated metabolite
      dehydroepiandrosterone sulphate (DHEA-S). The aim of this study is to investigate
      whether levels of DHEA and DHEA-S differ in individuals who report perceived
      stress at work compared to individuals who report no perceived stress at work.
      METHODS: Morning fasting DHEA-S and DHEA levels were measured in serum in a non
      stressed group (n = 40) and a stressed group (n = 41). DHEA and DHEA-S levels
      were compared between the groups using ANCOVA, controlling for age. RESULTS: The
      mean DHEA-S levels were 23% lower in the subjects who reported stress at work
      compared to the non-stressed group. Statistical analysis (ANCOVA) showed a
      significant difference in DHEA-S levels between the groups (p = 0.010). There was
      no difference in DHEA level between the groups. CONCLUSIONS: This study indicates
      that stressed individual have markedly lower levels of DHEA-S. Given the
      important and beneficial functions of DHEA and DHEA-S, lower levels of DHEA-S may
      constitute one link between psychosocial stress, ill health and accelerated
      ageing.

PMID- 24015248
TI  - Identification of putative steroid receptor antagonists in bottled water:
      combining bioassays and high-resolution mass spectrometry.
AB  - Endocrine disrupting chemicals (EDCs) are man-made compounds interfering with
      hormone signaling and thereby adversely affecting human health. Recent reports
      provide evidence for the presence of EDCs in commercially available bottled
      water, including steroid receptor agonists and antagonists. However, since these
      findings are based on biological data the causative chemicals remain unidentified
      and, therefore, inaccessible for toxicological evaluation. Thus, the aim of this
      study is to assess the antiestrogenic and antiandrogenic activity of bottled
      water and to identify the causative steroid receptor antagonists. We evaluated
      the antiestrogenic and antiandrogenic activity of 18 bottled water products in
      reporter gene assays for human estrogen receptor alpha and androgen receptor.
      Using nontarget high-resolution mass spectrometry (LTQ-Orbitrap Velos), we
      acquired corresponding analytical data. We combined the biological and chemical
      information to determine the exact mass of the tentative steroid receptor
      antagonist. Further MS(n) experiments elucidated the molecule's structure and
      enabled its identification. We detected significant antiestrogenicity in 13 of 18
      products. 16 samples were antiandrogenic inhibiting the androgen receptor by up
      to 90%. Nontarget chemical analysis revealed that out of 24520 candidates present
      in bottled water one was consistently correlated with the antagonistic activity.
      By combining experimental and in silico MS(n) data we identified this compound as
      di(2-ethylhexyl) fumarate (DEHF). We confirmed the identity and biological
      activity of DEHF and additional isomers of dioctyl fumarate and maleate using
      authentic standards. Since DEHF is antiestrogenic but not antiandrogenic we
      conclude that additional, yet unidentified EDCs must contribute to the
      antagonistic effect of bottled water. Applying a novel approach to combine
      biological and chemical analysis this is the first study to identify so far
      unknown EDCs in bottled water. Notably, dioctyl fumarates and maleates have been
      overlooked by science and regulation to date. This illustrates the need to
      identify novel toxicologically relevant compounds to establish a more holistic
      picture of the human exposome. 

PMID- 24015249
TI  - Autophagy plays a critical role in ChLym-1-induced cytotoxicity of non-hodgkin's
      lymphoma cells.
AB  - Autophagy is a critical mechanism in both cancer therapy resistance and tumor
      suppression. Monoclonal antibodies have been documented to kill tumor cells via
      apoptosis, antibody-dependent cellular cytotoxicity (ADCC) and complement
      dependent cytotoxicity (CDC). In this study, we report for the first time that
      chLym-1, a chimeric anti-human HLA-DR monoclonal antibody, induces autophagy in
      Raji Non-Hodgkin's Lymphoma (NHL) cells. Interestingly, inhibition of autophagy
      by pharmacological inhibitors (3-methyladenine and NH4Cl) or genetic approaches
      (siRNA targeting Atg5) suppresses chLym-1-induced growth inhibition, apoptosis,
      ADCC and CDC in Raji cells, while induction of autophagy could accelerate
      cytotoxic effects of chLym-1 on Raji cells. Furthermore, chLym-1-induced
      autophagy can mediate apoptosis through Caspase 9 activation, demonstrating the
      tumor-suppressing role of autophagy in antilymphoma effects of chLym-1. Moreover,
      chLym-1 can activate several upstream signaling pathways of autophagy including
      Akt/mTOR and extracellular signal-regulated kinase 1/2 (Erk1/2). These results
      elucidate the critical role of autophagy in cytotoxicity of chLym-1 antibody and
      suggest a potential therapeutic strategy of NHL therapy by monoclonal antibody
      chLym-1 in combination with autophagy inducer. 

PMID- 24015250
TI  - How television fast food marketing aimed at children compares with adult
      advertisements.
AB  - OBJECTIVES: Quick service restaurant (QSR) television advertisements for
      children's meals were compared with adult advertisements from the same companies
      to assess whether self-regulatory pledges for food advertisements to children had
      been implemented. METHODS: All nationally televised advertisements for the top 25
      US QSR restaurants from July 1, 2009 to June 30, 2010 were obtained and viewed to
      identify those advertising meals for children and these advertisements were
      compared with adult advertisements from the same companies. Content coding
      included visual and audio assessment of branding, toy premiums, movie tie-ins,
      and depictions of food. For image size comparisons, the diagonal length of the
      advertisement was compared with the diagonal length of salient food and drink
      images. RESULTS: Almost all of the 92 QSR children's meal advertisements that
      aired during the study period were attributable to McDonald's (70%) or Burger
      King (29%); 79% of 25,000 television placements aired on just four channels
      (Cartoon Network, Nickelodeon, Disney XD, and Nicktoons). Visual branding was
      more common in children's advertisements vs. adult advertisements, with food
      packaging present in 88% vs. 23%, and street view of the QSR restaurant present
      in 41% vs. 12%. Toy premiums or giveaways were present in 69% vs. 1%, and movie
      tie-ins present in 55% vs. 14% of children's vs. adult advertisements. Median
      food image diagonal length was 20% of the advertisement diagonal for children's
      and 45% for adult advertisements. The audio script for children's advertisements
      emphasized giveaways and movie tie-ins whereas adult advertisements emphasized
      food taste, price and portion size. CONCLUSIONS: Children's QSR advertisements
      emphasized toy giveaways and movie tie-ins rather than food products. Self
      regulatory pledges to focus on actual food products instead of toy premiums were
      not supported by this analysis.

PMID- 24015251
TI  - The role of explicit and implicit self-esteem in peer modeling of palatable food
      intake: a study on social media interaction among youngsters.
AB  - OBJECTIVE: This experimental study investigated the impact of peers on palatable
      food intake of youngsters within a social media setting. To determine whether
      this effect was moderated by self-esteem, the present study examined the roles of
      global explicit self-esteem (ESE), body esteem (BE) and implicit self-esteem
      (ISE). METHODS: Participants (N = 118; 38.1% boys; M age 11.14+/-.79) were asked
      to play a computer game while they believed to interact online with a same-sex
      normal-weight remote confederate (i.e., instructed peer) who ate either nothing,
      a small or large amount of candy. RESULTS: Participants modeled the candy intake
      of peers via a social media interaction, but this was qualified by their self
      esteem. Participants with higher ISE adjusted their candy intake to that of a
      peer more closely than those with lower ISE when the confederate ate nothing
      compared to when eating a modest (beta = .26, p = .05) or considerable amount of
      candy (kcal) (beta = .32, p = .001). In contrast, participants with lower BE
      modeled peer intake more than those with higher BE when eating nothing compared
      to a considerable amount of candy (kcal) (beta = .21, p = .02); ESE did not
      moderate social modeling behavior. In addition, participants with higher
      discrepant or "damaged" self-esteem (i.e., high ISE and low ESE) modeled peer
      intake more when the peer ate nothing or a modest amount compared to a
      substantial amount of candy (kcal) (beta = -.24, p = .004; beta = -.26, p<.0001,
      respectively). CONCLUSION: Youngsters conform to the amount of palatable food
      eaten by peers through social media interaction. Those with lower body esteem or
      damaged self-esteem may be more at risk to peer influences on food intake.

PMID- 24015252
TI  - Evolutionary history of the grey-faced Sengi, Rhynchocyon udzungwensis, from
      Tanzania: a molecular and species distribution modelling approach.
AB  - Rhynchocyon udzungwensis is a recently described and poorly understood sengi
      (giant elephant-shrew) endemic to two small montane forests in Southern Tanzania,
      and surrounded in lower forests by R. cirnei reichardi. In this study, we
      investigate the molecular genetic relationship between R. udzungwensis and R. c.
      reichardi, and the possible role that shifting species distributions in response
      to climate fluctuations may have played in shaping their evolutionary history.
      Rhynchocyon udzungwensis and R. c. reichardi individuals were sampled from five
      localities for genetic analyses. Three mitochondrial and two nuclear loci were
      used to construct species trees for delimitation and to determine whether
      introgression was detectable either from ancient or ongoing hybridization. All
      species-tree results show R. udzungwensis and R. c. reichardi as distinct
      lineages, though mtDNA shows evidence of introgression in some populations.
      Nuclear loci of each species were monophyletic, implying introgression is
      exclusively historical. Because we found evidence of introgression, we used
      distribution data and species distribution modelling for present, glacial, and
      interglacial climate cycles to predict how shifting species distributions may
      have facilitated hybridization in some populations. Though interpretations are
      affected by the limited range of these species, a likely scenario is that the
      mtDNA introgression found in eastern mid-elevation populations was facilitated by
      low numbers of R. udzungwensis that expanded into lowland heavily occupied R. c.
      reichardi areas during interglacial climate cycles. These results imply that
      relationships within the genus Rhynchocyon may be confounded by porous species
      boundaries and introgression, even if species are not currently sympatric. 

PMID- 24015253
TI  - Does the duration and time of sleep increase the risk of allergic rhinitis?
      Results of the 6-year nationwide Korea youth risk behavior web-based survey.
AB  - Allergic rhinitis (AR) is the most common chronic disorder in the pediatric
      population. Although several studies have investigated the correlation between AR
      and sleep-related issues, the association between the duration and time of sleep
      and AR has not been analyzed in long-term national data. This study investigated
      the relationship between sleep time and duration and AR risk in middle- and high
      school students (adolescents aged 12-18). We analyzed national data from the
      Korea Youth Risk Behavior Web-based Survey by the Korea Centers for Disease
      Control and Prevention from 2007-2012. The sample size was 274,480, with an
      average response rate of 96.2%. Multivariate logistic regression analyses were
      conducted to determine the relationship between sleep and AR risk. Furthermore,
      to determine the best-fitted model among independent variables such as sleep
      duration, sleep time, and the combination of sleep duration and sleep time, we
      used Akaike Information Criteria (AIC) to compare models. A total of 43,337 boys
      and 41,665 girls reported a diagnosis of AR at baseline. The odds ratio increased
      with age and with higher education and economic status of the parents. Further,
      students in mid-sized and large cities had stronger relationships to AR than
      those in small cities. In both genders, AR was associated with depression and
      suicidal ideation. In the analysis of sleep duration and sleep time, the odds
      ratio increased in both genders when sleep duration was <7 hours, and when the
      time of sleep was later than 24:00 hours. Our results indicate an association
      between sleep time and duration and AR. This study is the first to focus on the
      relationship between sleep duration and time and AR in national survey data
      collected over 6 years.

PMID- 24015254
TI  - Learning to obtain reward, but not avoid punishment, is affected by presence of
      PTSD symptoms in male veterans: empirical data and computational model.
AB  - Post-traumatic stress disorder (PTSD) symptoms include behavioral avoidance which
      is acquired and tends to increase with time. This avoidance may represent a
      general learning bias; indeed, individuals with PTSD are often faster than
      controls on acquiring conditioned responses based on physiologically-aversive
      feedback. However, it is not clear whether this learning bias extends to
      cognitive feedback, or to learning from both reward and punishment. Here, male
      veterans with self-reported current, severe PTSD symptoms (PTSS group) or with
      few or no PTSD symptoms (control group) completed a probabilistic classification
      task that included both reward-based and punishment-based trials, where feedback
      could take the form of reward, punishment, or an ambiguous "no-feedback" outcome
      that could signal either successful avoidance of punishment or failure to obtain
      reward. The PTSS group outperformed the control group in total points obtained;
      the PTSS group specifically performed better than the control group on reward
      based trials, with no difference on punishment-based trials. To better understand
      possible mechanisms underlying observed performance, we used a reinforcement
      learning model of the task, and applied maximum likelihood estimation techniques
      to derive estimated parameters describing individual participants' behavior.
      Estimations of the reinforcement value of the no-feedback outcome were
      significantly greater in the control group than the PTSS group, suggesting that
      the control group was more likely to value this outcome as positively reinforcing
      (i.e., signaling successful avoidance of punishment). This is consistent with the
      control group's generally poorer performance on reward trials, where reward
      feedback was to be obtained in preference to the no-feedback outcome. Differences
      in the interpretation of ambiguous feedback may contribute to the facilitated
      reinforcement learning often observed in PTSD patients, and may in turn provide
      new insight into how pathological behaviors are acquired and maintained in PTSD. 

PMID- 24015255
TI  - Evaluation of memory enhancing clinically available standardized extract of
      Bacopa monniera on P-glycoprotein and cytochrome P450 3A in Sprague-Dawley rats.
AB  - Bacopa monniera is a traditional Ayurvedic herbal medicine used to treat various
      mental ailments from ancient times. Recently, chemically standardized alcoholic
      extract of Bacopa monniera (BM) has been developed and currently available as
      over the counter herbal remedy for memory enhancement in children and adults.
      However, the consumption of herbal drugs has been reported to alter the
      expression of drug metabolizing enzymes and membrane transporters. Present study
      in male Sprague-Dawley rat was performed to evaluate the effect of memory
      enhancing standardized extract of BM on hepatic and intestinal cytochrome P450 3A
      and P-glycoprotein expression and activity. The BM (31 mg/kg/day) was orally
      administered for one week in BM pre-treated group while the control group
      received the same amount of vehicle for the same time period. The BM treatment
      decreased the cytochrome P450 3A (CYP3A) mediated testosterone 6beta
      hydroxylation activity of the liver and intestine by 2 and 1.5 fold, respectively
      compared to vehicle treated control. Similarly pretreatment with BM extract
      decreased the expression of intestinal P-glycoprotein (Pgp) as confirmed by
      Western blot analysis but did not alter the expression of hepatic Pgp. To
      investigate whether this BM pretreatment mediated decrease in activity of CYP3A
      and Pgp would account for the alteration of respective substrate or not,
      pharmacokinetic study with carbamazepine and digoxin was performed in BM pre
      treated rats and vehicle treated rats. Carbamazepine and digoxin were used as
      CYP3A and Pgp probe drugs, respectively. Significant increase in AUC and Cmax of
      carbamazepine (4 and 1.8 fold) and digoxin (1.3 and 1.2 fold), respectively
      following the BM pre-treatment confirmed the down regulation of CYP3A and Pgp. 

PMID- 24015256
TI  - Pseudomonas aeruginosa pyocyanin activates NRF2-ARE-mediated transcriptional
      response via the ROS-EGFR-PI3K-AKT/MEK-ERK MAP kinase signaling in pulmonary
      epithelial cells.
AB  - The redox-active pyocyanin (PCN) secreted by the respiratory pathogen Pseudomonas
      aeruginosa generates reactive oxygen species (ROS) and causes oxidative stress to
      pulmonary epithelial cells. Nuclear factor (erythroid-derived 2)-like 2 (NRF2)
      confers protection against ROS-mediated cell death by inducing the expression of
      detoxifying enzymes and proteins via its binding to the cis-acting antioxidant
      response element (ARE). However, a clear relationship between NRF2 and PCN
      mediated oxidative stress has not been established experimentally. In this study,
      we investigated the induction of NRF2-ARE response by PCN in the pulmonary
      epithelial cells. We analyzed the effect of PCN on NRF2 expression and nuclear
      translocation in cultured human airway epithelial cells, and in a mouse model of
      chronic PCN exposure. NRF2-dependent transcription of antioxidative enzymes was
      also assessed. Furthermore, we used inhibitors to examine the involvement of EGFR
      and its downstream signaling components that mediate NRF2-ARE-activation in
      response to PCN. PCN enhances the nuclear NRF2 accumulation and activates the
      transcription of ARE-mediated antioxidant genes. Furthermore, PCN activates NRF2
      by inducing the EGFR-phosphoinositide-3-kinase (PI3K) signaling pathway and its
      main downstream effectors, AKT and MEK1/2-ERK1/2 MAP kinases. Inhibition of the
      EGFR-PI3K signaling markedly attenuates PCN-stimulated NRF2 accumulation in the
      nucleus. We demonstrate for the first time that PCN-mediated oxidative stress
      activates the EGFR-PI3K-AKT/MEK1/2-ERK1/2 MAP kinase signaling pathway, leading
      to nuclear NRF2 translocation and ARE responsiveness in pulmonary epithelial
      cells. 

PMID- 24015257
TI  - Modulation of protease activated receptor 1 influences human metapneumovirus
      disease severity in a mouse model.
AB  - Human metapneumovirus (hMPV) infection causes acute respiratory tract infections
      (RTI) which can result in hospitalization of both children and adults. To date,
      no antiviral or vaccine is available for this common viral infection.
      Immunomodulators could represent an interesting strategy for the treatment of
      severe viral infection. Recently, the role of protease-activated receptors (PAR)
      in inflammation, coagulation and infection processes has been of growing
      interest. Herein, the effects of a PAR1 agonist and a PAR1 antagonist on hMPV
      infection were investigated in BALB/c mice. Intranasal administration of the PAR1
      agonist resulted in increased weight loss and mortality of infected mice.
      Conversely, the PAR1 antagonist was beneficial to hMPV infection by decreasing
      weight loss and clinical signs and by significantly reducing pulmonary
      inflammation, pro-inflammatory cytokine levels (including IL-6, KC and MCP-1) and
      recruitment of immune cells to the lungs. In addition, a significant reduction in
      pulmonary viral titers was also observed in the lungs of PAR1 antagonist-treated
      mice. Despite no apparent direct effect on virus replication during in vitro
      experiments, an important role for PAR1 in the regulation of furin expression in
      the lungs was shown for the first time. Further experiments indicated that the
      hMPV fusion protein can be cleaved by furin thus suggesting that PAR1 could have
      an effect on viral infectivity in addition to its immunomodulatory properties.
      Thus, inhibition of PAR1 by selected antagonists could represent an interesting
      strategy for decreasing the severity of paramyxovirus infections. 

PMID- 24015258
TI  - Clioquinol synergistically augments rescue by zinc supplementation in a mouse
      model of acrodermatitis enteropathica.
AB  - BACKGROUND: Zinc deficiency due to poor nutrition or genetic mutations in zinc
      transporters is a global health problem and approaches to providing effective
      dietary zinc supplementation while avoiding potential toxic side effects are
      needed. METHODS/PRINCIPAL FINDINGS: Conditional knockout of the intestinal zinc
      transporter Zip4 (Slc39a4) in mice creates a model of the lethal human genetic
      disease acrodermatitis enteropathica (AE). This knockout leads to acute zinc
      deficiency resulting in rapid weight loss, disrupted intestine integrity and
      eventually lethality, and therefore provides a model system in which to examine
      novel approaches to zinc supplementation. We examined the efficacy of dietary
      clioquinol (CQ), a well characterized zinc chelator/ionophore, in rescuing the
      Zip4 (intest KO) phenotype. By 8 days after initiation of the knockout neither
      dietary CQ nor zinc supplementation in the drinking water was found to be
      effective at improving this phenotype. In contrast, dietary CQ in conjunction
      with zinc supplementation was highly effective. Dietary CQ with zinc
      supplementation rapidly restored intestine stem cell division and differentiation
      of secretory and the absorptive cells. These changes were accompanied by rapid
      growth and dramatically increased longevity in the majority of mice, as well as
      the apparent restoration of the homeostasis of several essential metals in the
      liver. CONCLUSIONS: These studies suggest that oral CQ (or other 8
      hydroxyquinolines) coupled with zinc supplementation could provide a facile
      approach toward treating zinc deficiency in humans by stimulating stem cell
      proliferation and differentiation of intestinal epithelial cells.

PMID- 24015259
TI  - Circulating fibroblast growth factor 23 is associated with angiographic severity
      and extent of coronary artery disease.
AB  - OBJECTIVE: Fibroblast growth factor 23 (FGF23) is a circulating regulator of
      phosphate and vitamin D metabolism and is associated with coronary artery
      calcification, and has been implicated in the pathogenesis of cardiovascular
      disease. The aim of this study was to determine whether circulating FGF23
      concentration is independently associated with the severity and extent of
      coronary artery disease in patients undergoing coronary angiography. METHOD: A
      cross-sectional design was used to examine the relationship between serum FGF23
      and the severity and extent of coronary artery stenosis in 2076 patients
      undergoing coronary angiography (1263 male and 813 female, mean aged 62.5 years).
      Subgroup analyses were performed to assess the associations between FGF23 and
      coronary arterial plaque characteristics evaluated by intravascular ultrasound
      and 12-month incidence of target vessel revascularization (TVR) and target lesion
      revascularization (TLR). FINDINGS: We found a stepwise increase of serum FGF23
      concentrations in patients with mild, moderate, severe stenosis or with increased
      number of stenotic vessels compared with those without stenosis (P<0.001). Serum
      FGF23 concentration was positively correlated with stenosis scores as the global
      index of the severity and extent of coronary artery stenosis in both male and
      female (r = 0.315 and r = 0.291, P<0.001). In multiple regression analyses, serum
      FGF23 concentration was a significant determinant of the stenosis scores
      independent of other traditional risk factors (standardized beta = 0.326,
      P<0.001). Furthermore, subgroup analyses found FGF23 was significantly associated
      with plaque and dense calcium volumes. Multiple logistic regression analyses
      showed that serum FGF23 levels were significantly independent predictors of TVR
      and TLR. CONCLUSIONS: We report an independent association between circulating
      FGF23 concentration and the severity and extent of coronary artery stenosis in
      the coronary angiographic patients. Future studies are needed to elucidate the
      potential biological mechanisms and whether FGF23 is a modifiable cardiovascular
      risk factor.

PMID- 24015260
TI  - Lobesia botrana larvae develop faster in the presence of parasitoids.
AB  - To combat parasitism hosts often rely on their immune system, which is the last
      line of defense. However, the immune system may not always be effective, and
      other non-immunological defenses might be favored to reduce the cost of parasite
      infection. Here we report that larvae of the moth Lobesia botrana can rapidly
      accelerate their development and reach maturity earlier in response to cues
      perceived at a distance from parasitoids. Such a phenotypically plastic life
      history shift, induced by the perception of deadly enemies in the environment, is
      likely to be an adaptive defensive strategy to prevent parasitoid attack, and has
      important implications in host-parasite dynamics. 

PMID- 24015261
TI  - The Receptor-Bound Guanylyl Cyclase DAF-11 Is the Mediator of Hydrogen Peroxide
      Induced cGMP Increase in Caenorhabditis elegans [corrected]..
AB  - Adenosine 3', 5'-cyclic monophosphate (cAMP) and guanosine 3', 5'-cyclic
      monophosphate (cGMP) are well-studied second messengers that transmit
      extracellular signals into mammalian cells, with conserved functions in various
      other species such as Caenorhabditis elegans (C. elegans). cAMP is generated by
      adenylyl cyclases, and cGMP is generated by guanylyl cyclases, respectively.
      Studies using C. elegans have revealed additional roles for cGMP signaling in
      lifespan extension. For example, mutants lacking the function of a specific
      receptor-bound guanylyl cyclase, DAF-11, have an increased life expectancy. While
      the daf-11 phenotype has been attributed to reductions in intracellular cGMP
      concentrations, the actual content of cyclic nucleotides has not been
      biochemically determined in this system. Similar assumptions were made in studies
      using phosphodiesterase loss-of-function mutants or using adenylyl cyclase
      overexpressing mutants. In the present study, cyclic nucleotide regulation in C.
      elegans was studied by establishing a special nematode protocol for the
      simultaneous detection and quantitation of cyclic nucleotides. We also examined
      the influence of reactive oxygen species (ROS) on cyclic nucleotide metabolism
      and lifespan in C. elegans using highly specific HPLC-coupled tandem mass
      spectrometry and behavioral assays. Here, we show that the relation between cGMP
      and survival is more complex than previously appreciated. 

PMID- 24015262
TI  - Immunization of Mastomys coucha with Brugia malayi recombinant trehalose-6
      phosphate phosphatase results in significant protection against homologous
      challenge infection.
AB  - Development of a vaccine to prevent or reduce parasite development in lymphatic
      filariasis would be a complementary approach to existing chemotherapeutic tools.
      Trehalose-6-phosphate phosphatase of Brugia malayi (Bm-TPP) represents an
      attractive vaccine target due to its absence in mammals, prevalence in the major
      life stages of the parasite and immunoreactivity with human bancroftian
      antibodies, especially from endemic normal subjects. We have recently reported on
      the cloning, expression, purification and biochemical characterization of this
      vital enzyme of B. malayi. In the present study, immunoprophylactic evaluation of
      Bm-TPP was carried out against B. malayi larval challenge in a susceptible host
      Mastomys coucha and the protective ability of the recombinant protein was
      evaluated by observing the adverse effects on microfilarial density and adult
      worm establishment. Immunization caused 78.4% decrease in microfilaremia and
      71.04% reduction in the adult worm establishment along with sterilization of
      70.06% of the recovered live females. The recombinant protein elicited a mixed
      Th1/Th2 type of protective immune response as evidenced by the generation of both
      pro- and anti-inflammatory cytokines IL-2, IFN-gamma, TNF-alpha, IL-4 and an
      increased production of antibody isotypes IgG1, IgG2a, IgG2b and IgA. Thus
      immunization with Bm-TPP conferred considerable protection against B. malayi
      establishment by engendering a long-lasting effective immune response and
      therefore emerges as a potential vaccine candidate against lymphatic filariasis
      (LF). 

PMID- 24015263
TI  - Robots with display screens: a robot with a more humanlike face display is
      perceived to have more mind and a better personality.
AB  - It is important for robot designers to know how to make robots that interact
      effectively with humans. One key dimension is robot appearance and in particular
      how humanlike the robot should be. Uncanny Valley theory suggests that robots
      look uncanny when their appearance approaches, but is not absolutely, human. An
      underlying mechanism may be that appearance affects users' perceptions of the
      robot's personality and mind. This study aimed to investigate how robot facial
      appearance affected perceptions of the robot's mind, personality and eeriness. A
      repeated measures experiment was conducted. 30 participants (14 females and 16
      males, mean age 22.5 years) interacted with a Peoplebot healthcare robot under
      three conditions in a randomized order: the robot had either a humanlike face,
      silver face, or no-face on its display screen. Each time, the robot assisted the
      participant to take his/her blood pressure. Participants rated the robot's mind,
      personality, and eeriness in each condition. The robot with the humanlike face
      display was most preferred, rated as having most mind, being most humanlike,
      alive, sociable and amiable. The robot with the silver face display was least
      preferred, rated most eerie, moderate in mind, humanlikeness and amiability. The
      robot with the no-face display was rated least sociable and amiable. There was no
      difference in blood pressure readings between the robots with different face
      displays. Higher ratings of eeriness were related to impressions of the robot
      with the humanlike face display being less amiable, less sociable and less
      trustworthy. These results suggest that the more humanlike a healthcare robot's
      face display is, the more people attribute mind and positive personality
      characteristics to it. Eeriness was related to negative impressions of the
      robot's personality. Designers should be aware that the face on a robot's display
      screen can affect both the perceived mind and personality of the robot. 

PMID- 24015264
TI  - Relevance of baseline viral genetic heterogeneity and host factors for treatment
      outcome prediction in hepatitis C virus 1b-infected patients.
AB  - BACKGROUND: Only about 50% of patients chronically infected with HCV genotype 1
      (HCV-1) respond to treatment with pegylated interferon-alfa and ribavirin (dual
      therapy), and protease inhibitors have to be administered together with these
      drugs increasing costs and side-effects. We aimed to develop a predictive model
      of treatment response based on a combination of baseline clinical and viral
      parameters. METHODOLOGY: Seventy-four patients chronically infected with HCV-1b
      and treated with dual therapy were studied (53 retrospectively -training group-,
      and 21 prospectively -validation group-). Host and viral-related factors (viral
      load, and genetic variability in the E1-E2, core and Interferon Sensitivity
      Determining Region) were assessed. Multivariate discriminant analysis and
      decision tree analysis were used to develop predictive models on the training
      group, which were then validated in the validation group. PRINCIPAL FINDINGS: A
      multivariate discriminant predictive model was generated including the following
      variables in decreasing order of significance: the number of viral variants in
      the E1-E2 region, an amino acid substitution pattern in the viral core region,
      the IL28B polymorphism, serum GGT and ALT levels, and viral load. Using this
      model treatment outcome was accurately predicted in the training group (AUROC =
      0.9444; 96.3% specificity, 94.7% PPV, 75% sensitivity, 81% NPV), and the accuracy
      remained high in the validation group (AUROC = 0.8148, 88.9% specificity, 90.0%
      PPV, 75.0% sensitivity, 72.7% NPV). A second model was obtained by a decision
      tree analysis and showed a similarly high accuracy in the training group but a
      worse reproducibility in the validation group (AUROC = 0.9072 vs. 0.7361,
      respectively). CONCLUSIONS AND SIGNIFICANCE: The baseline predictive models
      obtained including both host and viral variables had a high positive predictive
      value in our population of Spanish HCV-1b treatment naive patients. Accurately
      identifying those patients that would respond to the dual therapy could help
      reducing implementation costs and additional side effects of new treatment
      regimens.

PMID- 24015265
TI  - Non-linear relationship between serum 25-hydroxyvitamin D and hemoglobin in
      Korean females: the Korean National Health and Nutrition Examination Survey 2010
      2011.
AB  - BACKGROUND: Anemia and vitamin D deficiency are both important health issues;
      however, the nature of the association between vitamin D and either hemoglobin or
      anemia remains unresolved in the general population. METHODS: Data on 11,206
      adults were obtained from the fifth Korean National Health and Nutritional
      Examination Survey. A generalized additive model was used to examine the
      threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and
      hemoglobin levels. A multivariate logistic regression for anemia was conducted
      according to 25(OH)D quintiles. All analyses were stratified according to sex and
      menstrual status. RESULTS: The generalized additive model confirmed a threshold
      25(OH)D level of 26.4 ng/mL (male, 27.4 ng/mL; premenopausal females, 11.8 ng/mL;
      postmenopausal females, 13.4 ng/mL). The threshold level affected the pattern of
      association between 25(OH)D and anemia risk: the odds ratio of the 1(st) quintile
      but not the 2(nd), 3(rd), and 4(th) quintiles were significantly different from
      the 5(th) quintile in both premenopausal and postmenopausal females, however
      there was no obvious trend in males. CONCLUSIONS: This population-based study
      demonstrated a non-linear relationship with a threshold effect between serum
      25(OH)D and hemoglobin levels in females. Further interventional studies are
      warranted to determine whether the appropriate level of hemoglobin can be
      achieved by the correction of vitamin D deficiency.

PMID- 24015266
TI  - Cross-linguistic similarity and task demands in Japanese-English bilingual
      processing.
AB  - Even in languages that do not share script, bilinguals process cognates faster
      than matched noncognates in a range of tasks. The current research more fully
      explores what underpins the cognate 'advantage' in different script bilinguals
      (Japanese-English). To do this, instead of the more traditional binary
      cognate/noncognate distinction, the current study uses continuous measures of
      phonological and semantic overlap, L2 (second language) proficiency and lexical
      variables (e.g., frequency). An L2 picture naming (Experiment 1) revealed a
      significant interaction between phonological and semantic similarity and
      demonstrates that degree of overlap modulates naming times. In lexical decision
      (Experiment 2), increased phonological similarity (e.g., bus/basu/vs.
      radio/rajio/) lead to faster response times. Interestingly, increased semantic
      similarity slowed response times in lexical decision. The studies also indicate
      how L2 proficiency and lexical variables modulate L2 word processing. These
      findings are explained in terms of current models of bilingual lexical
      processing. 

PMID- 24015267
TI  - Chronic cadmium exposure stimulates SDF-1 expression in an ERalpha dependent
      manner.
AB  - Cadmium is an omnipotent environmental contaminant associated with the
      development of breast cancer. Studies suggest that cadmium functions as an
      endocrine disruptor, mimicking the actions of estrogen in breast cancer cells and
      activating the receptor to promote cell growth. Although acute cadmium exposure
      is known to promote estrogen receptor-mediated gene expression associated with
      growth, the consequence of chronic cadmium exposure is unclear. Since heavy
      metals are known to bioaccumulate, it is necessary to understand the effects of
      prolonged cadmium exposure. This study aims to investigate the effects of chronic
      cadmium exposure on breast cancer progression. A MCF7 breast cancer cell line
      chronically exposed to 10(-7) M CdCl2 serves as our model system. Data suggest
      that prolonged cadmium exposures result in the development of more aggressive
      cancer phenotypes - increased cell growth, migration and invasion. The results
      from this study show for the first time that chronic cadmium exposure stimulates
      the expression of SDF-1 by altering the molecular interactions between ERalpha, c
      jun and c-fos. This study provides a mechanistic link between chronic cadmium
      exposure and ERalpha and demonstrates that prolonged, low-level cadmium exposure
      contributes to breast cancer progression. 

PMID- 24015268
TI  - Adenosine-mediated enteric neuromuscular function is affected during herpes
      simplex virus type 1 infection of rat enteric nervous system.
AB  - Adenosine plays an important role in regulating intestinal motility and
      inflammatory processes. Previous studies in rodent models have demonstrated that
      adenosine metabolism and signalling are altered during chronic intestinal
      inflammatory diseases. However, the involvement of the adenosinergic system in
      the pathophysiology of gut dysmotility associated to a primary neurodysfunction
      is still unclear. Recently, we showed that the neurotropic Herpes simplex virus
      type-1 (HSV-1), orally inoculated to rodents, infects the rat enteric nervous
      system (ENS) and affects gut motor function without signs of systemic infection.
      In this study we examined whether changes in purinergic metabolism and signaling
      occur during permanent HSV-1 infection of rat ENS. Using isolated organ bath
      assays, we found that contraction mediated by adenosine engagement of A1 or A2A
      receptors was impaired at 1 and 6 weeks post-viral administration.
      Immunofluorescence studies revealed that viral infection of ENS led to a marked
      redistribution of adenosine receptors: A1 and A2B receptors were confined to the
      muscle layers whereas A2A and A3 receptors were expressed mainly in the myenteric
      plexus. Viral-induced ENS neurodysfunction influenced adenosine metabolism by
      increasing adenosine deaminase and CD73 levels in longitudinal muscle-myenteric
      plexus with no sign of frank inflammation. This study provides the first evidence
      for involvement of the adenosinergic system during HSV-1 infection of the ENS. As
      such, this may represent a valid therapeutic target for modulating gut
      contractility associated to a primary neurodysfunction. 

PMID- 24015269
TI  - miR-26a suppresses tumor growth and metastasis by targeting FGF9 in gastric
      cancer.
AB  - The role of miR-26a in cancer cells seemed controversial in previous studies.
      Until now, the role of miR-26a in gastric cancer remains undefined. In this
      study, we found that miR-26a was strongly downregulated in gastric cancer (GC)
      tissues and cell lines, and its expression levels were associated with lymph node
      metastasis and clinical stage, as well as overall survival and replase-free
      survival of GC. We also found that ectopic expression of miR-26a inhibited GC
      cell proliferation and GC metastasis in vitro and in vivo. We further identified
      a novel mechanism of miR-26a to suppress GC growth and metastasis. FGF9 was
      proved to be a direct target of miR-26a, using luciferase assay and western blot.
      FGF9 overexpression in miR-26a-expressing cells could rescue invasion and growth
      defects of miR-26a. In addition, miR-26a expression inversely correlated with
      FGF9 protein levels in GC. Taken together, our data suggest that miR-26a
      functions as a tumor suppressor in GC development and progression, and holds
      promise as a prognostic biomarker and potential therapeutic target for GC. 

PMID- 24015270
TI  - Association between polymorphisms in the renin-angiotensin-aldosterone system
      genes and essential hypertension in the Han Chinese population.
AB  - BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) is the most important
      endocrine blood pressure control mechanism in our body, genes encoding components
      of this system have been strong candidates for the investigation of the genetic
      basis of hypertension. However, previous studies mainly focused on limited
      polymorphisms, thus we carried out a case-control study in the Han Chinese
      population to systemically investigate the association between polymorphisms in
      the RAAS genes and essential hypertension. METHODS: 905 essential hypertensive
      cases and 905 normotensive controls were recruited based on stringent inclusion
      and exclusion criteria. All 41 tagSNPs within RAAS genes were retrieved from
      HapMap, and the genotyping was performed using the GenomeLab SNPstream Genotyping
      System. Logistic regression analysis, Multifactor dimensionality reduction (MDR),
      stratified analysis and crossover analysis were used to identify and characterize
      interactions among the SNPs and the non-genetic factors. RESULTS: Serum levels of
      total cholesterol (TC) and triglyceride (TG), and body mass index (BMI) were
      significantly higher in the hypertensive group than in the control group. Of 41
      SNPs genotyped, rs3789678 and rs2493132 within AGT, rs4305 within ACE, rs275645
      within AGTR1, rs3802230 and rs10086846 within CYP11B2 were shown to associate
      with hypertension. The MDR analysis demonstrated that the interaction between BMI
      and rs4305 increased the susceptibility to hypertension. Crossover analysis and
      stratified analysis further indicated that BMI has a major effect, and rs4305 has
      a minor effect. CONCLUSION: These novel findings indicated that together with non
      genetic factors, these genetic variants in the RAAS may play an important role in
      determining an individual's susceptibility to hypertension in the Han Chinese.

PMID- 24015272
TI  - What are you or who are you? The emergence of social interaction between dog and
      an unidentified moving object (UMO).
AB  - Robots offer new possibilities for investigating animal social behaviour. This
      method enhances controllability and reproducibility of experimental techniques,
      and it allows also the experimental separation of the effects of bodily
      appearance (embodiment) and behaviour. In the present study we examined dogs'
      interactive behaviour in a problem solving task (in which the dog has no access
      to the food) with three different social partners, two of which were robots and
      the third a human behaving in a robot-like manner. The Mechanical UMO
      (Unidentified Moving Object) and the Mechanical Human differed only in their
      embodiment, but showed similar behaviour toward the dog. In contrast, the Social
      UMO was interactive, showed contingent responsiveness and goal-directed behaviour
      and moved along varied routes. The dogs showed shorter looking and touching
      duration, but increased gaze alternation toward the Mechanical Human than to the
      Mechanical UMO. This suggests that dogs' interactive behaviour may have been
      affected by previous experience with typical humans. We found that dogs also
      looked longer and showed more gaze alternations between the food and the Social
      UMO compared to the Mechanical UMO. These results suggest that dogs form
      expectations about an unfamiliar moving object within a short period of time and
      they recognise some social aspects of UMOs' behaviour. This is the first evidence
      that interactive behaviour of a robot is important for evoking dogs' social
      responsiveness. 

PMID- 24015271
TI  - Protective but not anticonvulsant effects of ghrelin and JMV-1843 in the
      pilocarpine model of Status epilepticus.
AB  - In models of status epilepticus ghrelin displays neuroprotective effects mediated
      by the growth hormone secretagogue-receptor 1a (GHS-R1a). This activity may be
      explained by anticonvulsant properties that, however, are controversial. We
      further investigated neuroprotection and the effects on seizures by comparing
      ghrelin with a more effective GHS-R1a agonist, JMV-1843. Rats were treated either
      with ghrelin, JMV-1843 or saline 10 min before pilocarpine, which was used to
      induce status epilepticus. Status epilepticus, developed in all rats, was
      attenuated by diazepam. No differences were observed among the various groups in
      the characteristics of pilocarpine-induced seizures. In saline group the area of
      lesion, characterized by lack of glial fibrillary acidic protein
      immunoreactivity, was of 0.45 +/- 0.07 mm(2) in the hippocampal stratum lacunosum
      moleculare, and was accompanied by upregulation of laminin immunostaining, and by
      increased endothelin-1 expression. Both ghrelin (P<0.05) and JMV-1843 (P<0.01)
      were able to reduce the area of loss in glial fibrillary acidic protein
      immunostaining. In addition, JMV-1843 counteracted (P<0.05) the changes in
      laminin and endothelin-1 expression, both increased in ghrelin-treated rats. JMV
      1843 was able to ameliorate neuronal survival in the hilus of dentate gyrus and
      medial entorhinal cortex layer III (P<0.05 vs saline and ghrelin groups). These
      results demonstrate diverse protective effects of growth hormone secretagogues in
      rats exposed to status epilepticus.

PMID- 24015273
TI  - Metabolome-wide association study of neovascular age-related macular
      degeneration.
AB  - PURPOSE: To determine if plasma metabolic profiles can detect differences between
      patients with neovascular age-related macular degeneration (NVAMD) and similarly
      aged controls. METHODS: Metabolomic analysis using liquid chromatography with
      Fourier-transform mass spectrometry (LC-FTMS) was performed on plasma samples
      from 26 NVAMD patients and 19 controls. Data were collected from mass/charge
      ratio (m/z) 85 to 850 on a Thermo LTQ-FT mass spectrometer, and metabolic
      features were extracted using an adaptive processing software package. Both non
      transformed and log2 transformed data were corrected using Benjamini and Hochberg
      False Discovery Rate (FDR) to account for multiple testing. Orthogonal Partial
      Least Squares-Discriminant Analysis was performed to determine metabolic features
      that distinguished NVAMD patients from controls. Individual m/z features were
      matched to the Kyoto Encyclopedia of Genes and Genomes database and the Metlin
      metabolomics database, and metabolic pathways associated with NVAMD were
      identified using MetScape. RESULTS: Of the 1680 total m/z features detected by LC
      FTMS, 94 unique m/z features were significantly different between NVAMD patients
      and controls using FDR (q = 0.05). A comparison of these features to those found
      with log2 transformed data (n = 132, q = 0.2) revealed 40 features in common,
      reaffirming the involvement of certain metabolites. Such metabolites included di-
      and tripeptides, covalently modified amino acids, bile acids, and vitamin D
      related metabolites. Correlation analysis revealed associations among certain
      significant features, and pathway analysis demonstrated broader changes in
      tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to
      urea metabolism. CONCLUSIONS: These data suggest that metabolomic analysis can
      identify a panel of individual metabolites that differ between NVAMD cases and
      controls. Pathway analysis can assess the involvement of certain metabolic
      pathways, such as tyrosine and urea metabolism, and can provide further insight
      into the pathophysiology of AMD.

PMID- 24015274
TI  - Dynamics of Notch pathway expression during mouse testis post-natal development
      and along the spermatogenic cycle.
AB  - The transcription and expression patterns of Notch pathway components (Notch 1-3,
      Delta1 and 4, Jagged1) and effectors (Hes1, Hes2, Hes5 and Nrarp) were evaluated
      (through RT-PCR and IHC) in the mouse testis at key moments of post-natal
      development, and along the adult spermatogenic cycle. Notch pathway components
      and effectors are transcribed in the testis and expressed in germ, Sertoli and
      Leydig cells, and each Notch component shows a specific cell-type and time-window
      expression pattern. This expression at key testis developmental events prompt for
      a role of Notch signaling in pre-pubertal spermatogonia quiescence, onset of
      spermatogenesis, and regulation of the spermatogenic cycle. 

PMID- 24015275
TI  - Interleukin 13 and serotonin: linking the immune and endocrine systems in murine
      models of intestinal inflammation.
AB  - OBJECTIVE: Infiltration of activated immune cells and increased cytokine
      production define the immunophenotype of gastrointestinal (GI) inflammation. In
      addition, intestinal inflammation is accompanied by alteration in the numbers of
      serotonin (5-hydroxytryptamine; 5-HT) synthesizing enterochromaffin (EC) cells
      and in 5-HT amount. It has been established that EC cells express interleukin
      (IL)-13 receptor, additionally IL-13 has been implicated in the pathogenesis of
      ulcerative colitis. In this study, we investigated the role of IL-13 mediated 5
      HT signaling in pathogenesis of colitis. METHODOLOGY: Colitis was induced in IL
      13 deficient (IL-13-/-) and wild-type (WT) mice with dextran sulfate sodium (DSS)
      and dinitrobenzene sulfonic acid (DNBS), as well as in IL-13-/- mice given
      recombinant mouse IL-13 (rmIL-13) and 5-hydroxytryptamine (5-HTP), the direct
      precursor of 5-HT. PRINCIPAL FINDINGS AND CONCLUSION: Elevated colonic IL-13
      levels were observed in WT mice receiving DSS in comparison to control. IL-13-/-
      mice administered DSS exhibited significantly reduced severity of colitis
      compared to WT mice as reflected by macroscopic and histological damage
      assessments. Following DSS administration, significantly lower pro-inflammatory
      cytokine production and fewer infiltrating macrophages were observed in IL-13-/-
      mice compared to WT. The reduced severity of colitis observed in IL-13-/- mice
      was also accompanied by down-regulation of EC cell numbers and colonic 5-HT
      content. In addition, increasing colonic 5-HT content by administration of rmIL
      13 or 5-HTP exacerbated severity of DSS colitis in IL-13-/- mice. IL-13-/- mice
      also exhibited reduced severity of DNBS-induced colitis. These results
      demonstrate that IL-13 plays a critical role in the pathogenesis of experimental
      colitis and 5-HT is an important mediator of IL-13 driven intestinal
      inflammation. This study revealed important information on immune-endocrine axis
      in gut in relation to inflammation which may ultimately lead to better strategy
      in managing various intestinal inflammatory conditions including inflammatory
      bowel disease.

PMID- 24015276
TI  - Pancreatic duct patterns in acute pancreatitis: a MRI study.
AB  - OBJECTIVES: To study the MRI findings of the pancreatic duct in patients with
      acute pancreatitis. MATERIALS AND METHODS: A total of 239 patients with acute
      pancreatitis and 125 controls were analyzed in this study. The severity of acute
      pancreatitis was graded using the MR severity index (MRSI) and the Acute
      Physiology And Chronic Healthy Evaluation II(APACHE II) scoring systems. The
      number of main pancreatic duct (MPD) segments visualized, and both MPD diameter
      and pancreatic duct disruption were noted and compared with the severity of acute
      pancreatitis. RESULTS: The frequency of MPD segment visualization in the control
      group was higher than that in the acute pancreatitis group (p<0.05). The number
      of MPD segments visualized was negatively correlated with the MRSI score (p<0.05)
      and the APACHE II score (p<0.05). There was no difference in the MPD diameter
      between the acute pancreatitis and control groups or among the patients with
      different severities of acute pancreatitis (p>0.05). The prevalence of pancreatic
      duct disruption was 7.9% in the acute pancreatitis group. The prevalences of
      pancreatic duct disruption were 4.8% and 15.3% in the mild and severe acute
      pancreatitis groups based on the APACHE II score, respectively, and were 0%, 5.7%
      and 43.5% in the mild, moderate and severe acute pancreatitis groups according
      the MRSI score, respectively. The prevalence of pancreatic duct disruption was
      correlated with the severity of acute pancreatitis based on the APACHE II score
      (p<0.05) and MRSI score (p<0.05). CONCLUSION: The pancreatic duct in acute
      pancreatitis patients was of normal diameter. The number of MPD segments
      visualized and visible pancreatic duct disruption on MRI may be supplementary
      indicators for determining the severity of acute pancreatitis.

PMID- 24015278
TI  - Reef odor: a wake up call for navigation in reef fish larvae.
AB  - The behavior of reef fish larvae, equipped with a complex toolbox of sensory
      apparatus, has become a central issue in understanding their transport in the
      ocean. In this study pelagic reef fish larvae were monitored using an unmanned
      open-ocean tracking device, the drifting in-situ chamber (DISC), deployed
      sequentially in oceanic waters and in reef-born odor plumes propagating offshore
      with the ebb flow. A total of 83 larvae of two taxonomic groups of the families
      Pomacentridae and Apogonidae were observed in the two water masses around One
      Tree Island, southern Great Barrier Reef. The study provides the first in-situ
      evidence that pelagic reef fish larvae discriminate reef odor and respond by
      changing their swimming speed and direction. It concludes that reef fish larvae
      smell the presence of coral reefs from several kilometers offshore and this odor
      is a primary component of their navigational system and activates other
      directional sensory cues. The two families expressed differences in their
      response that could be adapted to maintain a position close to the reef. In
      particular, damselfish larvae embedded in the odor plume detected the location of
      the reef crest and swam westward and parallel to shore on both sides of the
      island. This study underlines the critical importance of in situ Lagrangian
      observations to provide unique information on larval fish behavioral decisions.
      From an ecological perspective the central role of olfactory signals in marine
      population connectivity raises concerns about the effects of pollution and
      acidification of oceans, which can alter chemical cues and olfactory responses. 

PMID- 24015277
TI  - Immunogenicity of seven-valent pneumococcal conjugate vaccine administered at 6,
      14 and 40 weeks of age in South African infants.
AB  - BACKGROUND: The high cost of pneumococcal conjugate vaccine (PCV) and local
      epidemiological factors contributed to evaluating different PCV dosing-schedules.
      This study evaluated the immunogenicity of seven-valent PCV (PCV7) administered
      at 6-weeks; 14-weeks and 9-months of age. METHODS: 250 healthy, HIV-unexposed
      infants were immunized with PCV7 concurrently with other childhood vaccines.
      Serotype-specific anti-capsular IgG concentrations were measured one-month
      following the 1(st) and 2(nd) PCV-doses, prior to and two-weeks following the
      3(rd) dose. Opsonophagocytic killing assay (OPA) was measured for three serotypes
      following the 2(nd) and 3(rd) PCV7-doses. Immunogenicity of the current schedule
      was compared to a historical cohort of infants who received PCV7 at 6, 10 and 14
      weeks of age. RESULTS: The proportion of infants with serotype-specific antibody
      >= 0.35 ug/ml following the 2(nd) PCV7-dose ranged from 84% for 6B to >= 89% for
      other serotypes. Robust antibody responses were observed following the 3(rd)
      dose. The proportion of children with OPA >= 8 for serotypes 9V, 19F and 23F
      increased significantly following the 3(rd) PCV7-dose to 93.6%; 86.0% and 89.7%
      respectively. The quantitative antibody concentrations following the 2(nd) PCV7
      dose were comparable to that after the 3(rd) -dose in the 6-10-14 week schedule.
      Geometric mean concentrations (GMCs) following the 3(rd) PCV7-dose were higher
      for all serotypes in this study compared to the historical cohort. CONCLUSIONS:
      The studied PCV7 dosing schedule induced good immune responses, including higher
      GMCs following the 3(rd-)dose at 9-months compared to when given at 14-weeks of
      age. This may confer longer persistence of antibodies and duration of protection
      against pneumococcal disease.

PMID- 24015279
TI  - Identification of MiRNA from eggplant (Solanum melongena L.) by small RNA deep
      sequencing and their response to Verticillium dahliae infection.
AB  - MiRNAs are a class of non-coding small RNAs that play important roles in the
      regulation of gene expression. Although plant miRNAs have been extensively
      studied in model systems, less is known in other plants with limited genome
      sequence data, including eggplant (Solanum melongena L.). To identify miRNAs in
      eggplant and their response to Verticillium dahliae infection, a fungal pathogen
      for which clear understanding of infection mechanisms and effective cure methods
      are currently lacking, we deep-sequenced two small RNA (sRNA) libraries prepared
      from mock-infected and infected seedlings of eggplants. Specifically, 30,830,792
      reads produced 7,716,328 unique miRNAs representing 99 known miRNA families that
      have been identified in other plant species. Two novel putative miRNAs were
      predicted with eggplant ESTs. The potential targets of the identified known and
      novel miRNAs were also predicted based on sequence homology search. It was
      observed that the length distribution of obtained sRNAs and the expression of 6
      miRNA families were obviously different between the two libraries. These results
      provide a framework for further analysis of miRNAs and their role in regulating
      plant response to fungal infection and Verticillium wilt in particular. 

PMID- 24015280
TI  - Spontaneous ejaculation in a wild Indo-Pacific bottlenose dolphin (Tursiops
      aduncus).
AB  - Spontaneous ejaculation, which is defined as the release of seminal fluids
      without apparent sexual stimulation, has been documented in boreoeutherian
      mammals. Here we report spontaneous ejaculation in a wild Indo-Pacific bottlenose
      dolphin (Tursiops aduncus), and present a video of this rare behavior. This is
      the first report of spontaneous ejaculation by an aquatic mammal, and the first
      video of this behavior in animals to be published in a scientific journal. 

PMID- 24015281
TI  - Crystal structure and substrate specificity of D-galactose-6-phosphate isomerase
      complexed with substrates.
AB  - D-Galactose-6-phosphate isomerase from Lactobacillus rhamnosus (LacAB; EC
      5.3.1.26), which is encoded by the tagatose-6-phosphate pathway gene cluster
      (lacABCD), catalyzes the isomerization of D-galactose-6-phosphate to D-tagatose-6
      phosphate during lactose catabolism and is used to produce rare sugars as low
      calorie natural sweeteners. The crystal structures of LacAB and its complex with
      D-tagatose-6-phosphate revealed that LacAB is a homotetramer of LacA and LacB
      subunits, with a structure similar to that of ribose-5-phosphate isomerase (Rpi).
      Structurally, LacAB belongs to the RpiB/LacAB superfamily, having a Rossmann-like
      alphabetaalpha sandwich fold as has been identified in pentose phosphate
      isomerase and hexose phosphate isomerase. In contrast to other family members,
      the LacB subunit also has a unique alpha7 helix in its C-terminus. One active
      site is distinctly located at the interface between LacA and LacB, whereas two
      active sites are present in RpiB. In the structure of the product complex, the
      phosphate group of D-tagatose-6-phosphate is bound to three arginine residues,
      including Arg-39, producing a different substrate orientation than that in RpiB,
      where the substrate binds at Asp-43. Due to the proximity of the Arg-134 residue
      and backbone Calpha of the alpha6 helix in LacA to the last Asp-172 residue of
      LacB with a hydrogen bond, a six-carbon sugar-phosphate can bind in the larger
      pocket of LacAB, compared with RpiB. His-96 in the active site is important for
      ring opening and substrate orientation, and Cys-65 is essential for the
      isomerization activity of the enzyme. Two rare sugar substrates, D-psicose and D
      ribulose, show optimal binding in the LacAB-substrate complex. These findings
      were supported by the results of LacA activity assays. 

PMID- 24015282
TI  - Proteomic analysis of the function of sigma factor sigma54 in Helicobacter pylori
      survival with nutrition deficiency stress in vitro.
AB  - H. pylori can survive under a nutrition-deficient environment. During infection
      and transmission, H. pylori is confronted with nutrient limitation and the
      bacterium requires rapid alteration in gene expression for survival under stress
      conditions. However, the mechanism underlining this regulation remains unknown. A
      previous study showed that sigma(54) is an important regulation factor for H.
      pylori survival in the nutrition-deficient environment. Our results show that the
      expression of sigma(54) (rpoN) is significantly induced in the stationary phase
      (nutrition deficiency) and the rpoN mutant showed a significantly lower viability
      than wild-type H. pylori in the late stationary phase. Thus, sigma(54) is
      involved in H. pylori survival during nutrient limitation. We used comparative
      proteomics to analyze the protein differentiation between wild-type and rpoN
      mutant during the stationary phase. With depleted nutrients, sigma(54) can slow
      the process of proliferation by negatively regulating genes involved in energy
      metabolism and biosynthesis and enhance stress-resistant ability by positively
      regulating genes involved in protein fate and redox reaction. Especially, NapA
      positively regulated by sigma(54) plays an important function in H. pylori
      survival both in the stationary phase and in water, and the latter situation
      would be beneficial for bacterial in vitro transmission. Our investigations give
      new light on the adaptive regulation of H. pylori under stress conditions. 

PMID- 24015283
TI  - Errors in recall of age at first sex.
AB  - AIMS: To measure the degree and direction of errors in recall of age at first
      sex. METHOD: Participants were initially recruited in 1994-1995 (Wave I) with 3
      subsequent follow-ups in: 1996 (Wave II); 2001- 2002 (Wave III); and 2007-2008
      (Wave IV). Participants' individual errors in recall of their age at first sex at
      Wave IV were estimated by the paired difference between responses given for age
      at first sex in Wave I and Wave IV (recalled age at first sex obtained at Wave IV
      minus the age at first sex obtained at Wave I). RESULTS: The mean of the recall
      estimation of age at first sex at Wave IV was found to be slightly increased
      comparing to the age at first sex at Wave I (less than 1 year). The errors in the
      recalled age at first sex tended to increase in participants who had their first
      sex younger or older than the average, and the recalled age at first sex tended
      to bias towards the mean (i.e. participants who had first sex younger than the
      average were more likely to recall an age at first sex that was older than the
      age, and vice versa). CONCLUSIONS: In this U.S. population-based sample, the
      average recall error for age at first sex was small. However, the accuracy of
      recalled information varied significantly among subgroup populations.

PMID- 24015284
TI  - Aflatoxin B1 negatively regulates Wnt/beta-catenin signaling pathway through
      activating miR-33a.
AB  - MicroRNAs are known to play an important role in modulating gene expression in
      various diseases including cancers and cardiovascular disorders, but only a few
      of them are associated with the pathology of aflatoxin B1 (AFB1), a potent
      mycotoxin. Here, we discovered a novel regulatory network between AFB1, miR-33a
      and beta-catenin in human carcinoma cells. The level of miR-33a was up-regulated
      in hepatocellular carcinoma (HCC) cells treated with AFB1, while in the same
      cells causing the decrease in beta-catenin expression when treated at their IC50
      values. miR-33a, specifically miR-33a-5p, was demonstrated to down-regulate the
      expression of beta-catenin, affect the beta-catenin pathway, and inhibit cell
      growth. Also, by employing a luciferase assay, we found that miR-33a down
      regulated beta-catenin by directly binding to the 3'-UTR of beta-catenin. These
      results suggested that AFB1 might down-regulate beta-catenin by up-regulating miR
      33a. This understanding opens new lines of thought in the potential role of miR
      33a in the clinical therapy of cancer. 

PMID- 24015285
TI  - Strategy to better select HIV-infected individuals for latent TB treatment in BCG
      vaccinated population.
AB  - OBJECTIVE: To evaluate the T-SPOT.TB interferon-gamma releasing assay and the
      tuberculin skin test (TST), for the diagnosis of latent tuberculosis
      infection(LTBI) and the development of subsequent active tuberculosis, in BCG
      vaccinated HIV-infected individuals. METHODS: HIV-infected individuals without
      clinical suspicion of active TB or a past history of TB were enrolled from 1
      January 2008 to 30 November 2010. Both T-SPOT.TB test and TST were offered to the
      participants whom were followed up prospectively until April 30, 2012 for
      development of TB. RESULTS: Among the 909 participants, 25% had positive TST
      reactions with cut-off point of 5 mm and 15% had positive T-SPOT.TB results.
      After a median follow-up of 2.97 years, there were 5 cases developed culture
      confirmed active TB (all had dual positive TST and T-SPOT.TB results), and the
      incidence was 0.17 per 100 person-years. The relative risks (RRs) for subsequent
      active TB in HIV-infected individuals with positive TST results, positive T
      SPOT.TB results and dual positive results compared with the risk for individuals
      with negative results were 40.6 (95% CI 2.1-767.9), 73.9 (95% CI 3.9-1397.7) and
      226.5 (95% CI 12.0-4284), respectively. The number needed to treat to prevent one
      subsequent TB case among patients with a positive TST, a positive T-SPOT.TB and
      dual positive results was 35, 22 and 8 respectively. CONCLUSIONS: Adopting
      positive results of the TST and T-SPOT.TB to screen LTBI among BCG-vaccinated HIV
      infected individuals might be feasible. Number needed to treat for isoniazid
      preventive therapy could be reduced significantly by using dual positive
      strategy.

PMID- 24015286
TI  - A second tubulin binding site on the kinesin-13 motor head domain is important
      during mitosis.
AB  - Kinesin-13s are microtubule (MT) depolymerases different from most other kinesins
      that move along MTs. Like other kinesins, they have a motor or head domain (HD)
      containing a tubulin and an ATP binding site. Interestingly, kinesin-13s have an
      additional binding site (Kin-Tub-2) on the opposite side of the HD that contains
      several family conserved positively charged residues. The role of this site in
      kinesin-13 function is not clear. To address this issue, we investigated the in
      vitro and in-vivo effects of mutating Kin-Tub-2 family conserved residues on the
      Drosophila melanogaster kinesin-13, KLP10A. We show that the Kin-Tub-2 site
      enhances tubulin cross-linking and MT bundling properties of KLP10A in-vitro.
      Disruption of the Kin-Tub-2 site, despite not having a deleterious effect on MT
      depolymerization, results in abnormal mitotic spindles and lagging chromosomes
      during mitosis in Drosophila S2 cells. The results suggest that the additional
      Kin-Tub-2 tubulin biding site plays a direct MT attachment role in-vivo. 

PMID- 24015288
TI  - Characterization of the Arabidopsis thaliana E3 ubiquitin-ligase AtSINAL7 and
      identification of the ubiquitination sites.
AB  - Protein ubiquitination leading to degradation by the proteasome is an important
      mechanism in regulating key cellular functions. Protein ubiquitination is carried
      out by a three step process involving ubiquitin (Ub) activation by a E1 enzyme,
      the transfer of Ub to a protein E2, finally an ubiquitin ligase E3 catalyzes the
      transfer of the Ub peptide to an acceptor protein. The E3 component is
      responsible for the specific recognition of the target, making the unveiling of
      E3 components essential to understand the mechanisms regulating fundamental cell
      processes through the protein degradation pathways. The Arabidopsis thaliana
      seven in absentia-like 7 (AtSINAL7) gene encodes for a protein with
      characteristics from a C3HC4-type E3 ubiquitin ligase. We demonstrate here that
      AtSINAL7 protein is indeed an E3 protein ligase based on the self-ubiquitination
      in vitro assay. This activity is dependent of the presence of a Lys residue in
      position 124. We also found that higher AtSINAL7 transcript levels are present in
      tissues undergoing active cell division during floral development. An interesting
      observation is the circadian expression pattern of AtSINAL7 mRNA in floral buds.
      Furthermore, UV-B irradiation induces the expression of this transcript
      indicating that AtSINAL7 may be involved in a wide range of different cell
      processes. 

PMID- 24015287
TI  - LRRK2 and RIPK2 variants in the NOD 2-mediated signaling pathway are associated
      with susceptibility to Mycobacterium leprae in Indian populations.
AB  - In recent years, genome wide association studies have discovered a large number
      of gene loci that play a functional role in innate and adaptive immune pathways
      associated with leprosy susceptibility. The immunological control of
      intracellular bacteria M. leprae is modulated by NOD2-mediated signaling of Th1
      responses. In this study, we investigated 211 clinically classified leprosy
      patients and 230 ethnically matched controls in Indian population by genotyping
      four variants in NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), RIPK2 (rs40457A/G and
      rs42490G/A). The LRRK2 locus is associated with leprosy outcome. The LRRK2
      rs1873613A minor allele and respective rs1873613AA genotypes were significantly
      associated with an increased risk whereas the LRRK2 rs1873613G major allele and
      rs1873613GG genotypes confer protection in paucibacillary and leprosy patients.
      The reconstructed GA haplotypes from RIPK2 rs40457A/G and rs42490G/A variants was
      observed to contribute towards increased risk whereas haplotypes AA was observed
      to confer protective role. Our results indicate that a possible shared mechanisms
      underlying the development of these two clinical forms of the disease as
      hypothesized. Our findings confirm and validates the role of gene variants
      involved in NOD2-mediated signalling pathways that play a role in immunological
      control of intracellular bacteria M. leprae. 

PMID- 24015289
TI  - The soluble receptor for vitamin B12 uptake (sCD320) increases during pregnancy
      and occurs in higher concentration in urine than in serum.
AB  - BACKGROUND: Cellular uptake of vitamin B12 (B12) demands binding of the vitamin
      to transcobalamin (TC) and recognition of TC-B12 (holoTC) by the receptor CD320,
      a receptor expressed in high quantities on human placenta. We have identified a
      soluble form of CD320 (sCD320) in serum and here we present data on the
      occurrence of this soluble receptor in both serum and urine during pregnancy.
      METHODS: We examined serum from twenty-seven pregnant women (cohort 1) at
      gestational weeks 13, 24 and 36 and serum and urine samples from forty pregnant
      women (cohort 2) tested up to 8 times during gestational weeks 17-41. sCD320,
      holoTC, total TC and complex formation between holoTC and sCD320 were measured by
      in-house ELISA methods, while creatinine was measured on the automatic platform
      Cobas 6000. Size exclusion chromatography was performed on a Superdex 200 column.
      RESULTS: Median (range) of serum sCD320 increased from 125 (87-839) pmol/L (week
      15) to reach a peak value of 199 (72-672) pmol/L (week 35) then dropped back to
      its baseline level just before birth (week 40). Around one third of sCD320 was
      precipitated with holoTC at all-time points studied. The urinary concentration of
      sCD320 was around two fold higher than in serum. Urinary sCD320/creatinine ratio
      correlated with serum sCD320 and reached a peak median level of 53 (30-101)
      pmol/mmol creatinine (week 35). sCD320 present in serum and urine showed the same
      elution pattern upon size exclusion chromatography. CONCLUSION: We report for the
      first time that sCD320 is present in urine and in a higher concentration than in
      serum and that serum and urine sCD320 increase during pregnancy. The high urinary
      concentration and the strong correlation between urinary and serum sCD320
      suggests that sCD320 is filtered in the kidney.

PMID- 24015290
TI  - Formation of a unique cluster of G-quadruplex structures in the HIV-1 Nef coding
      region: implications for antiviral activity.
AB  - G-quadruplexes are tetraplex structures of nucleic acids that can form in G-rich
      sequences. Their presence and functional role have been established in telomeres,
      oncogene promoters and coding regions of the human chromosome. In particular,
      they have been proposed to be directly involved in gene regulation at the level
      of transcription. Because the HIV-1 Nef protein is a fundamental factor for
      efficient viral replication, infectivity and pathogenesis in vitro and in vivo,
      we investigated G-quadruplex formation in the HIV-1 nef gene to assess the
      potential for viral inhibition through G-quadruplex stabilization. A
      comprehensive computational analysis of the nef coding region of available
      strains showed the presence of three conserved sequences that were uniquely
      clustered. Biophysical testing proved that G-quadruplex conformations were
      efficiently stabilized or induced by G-quadruplex ligands in all three sequences.
      Upon incubation with a G-quadruplex ligand, Nef expression was reduced in a
      reporter gene assay and Nef-dependent enhancement of HIV-1 infectivity was
      significantly repressed in an antiviral assay. These data constitute the first
      evidence of the possibility to regulate HIV-1 gene expression and infectivity
      through G-quadruplex targeting and therefore open a new avenue for viral
      treatment. 

PMID- 24015291
TI  - Poor metabolizers at the cytochrome P450 2C19 loci is at increased risk of
      developing cancer in Asian populations.
AB  - BACKGROUND: CYP2C19 encodes a member of the cytochrome P450 superfamily of
      enzymes, which play a central role in activating and detoxifying many carcinogens
      and endogenous compounds thought to be involved in the development of cancer. In
      the past decade, two common polymorphisms among CYP2C19 (CYP2C19*2 and CYP2C19*3)
      that are responsible for the poor metabolizers (PMs) phenotype in humans and
      cancer susceptibility have been investigated extensively; however, these studies
      have yielded contradictory results. METHODS AND RESULTS: To investigate this
      inconsistency, we conducted a comprehensive meta-analysis of 11,554 cases and
      16,592 controls from 30 case-control studies. Overall, the odds ratio (OR) of
      cancer was 1.52 [95% confidence interval (CI): 1.23-1.88, P<10(-4)] for CYP2C19
      PMs genotypes. However, this significant association vanished when the analyses
      were restricted to 5 larger studies (no. of cases >= 500 cases). In the subgroup
      analysis for different cancer types, PMs genotypes had an effect of increasing
      the risks of esophagus cancer, gastric cancer, lung cancer and hepatocellular
      carcinoma as well as head neck cancer. Significant results were found in Asian
      populations when stratified by ethnicity; whereas no significant associations
      were found among Caucasians. Stratified analyses according to source of controls,
      significant associations were found only in hospital base controls. CONCLUSIONS:
      Our meta-analysis suggests that the CYP2C19 PMs genotypes most likely contributes
      to cancer susceptibility, particularly in the Asian populations.

PMID- 24015292
TI  - Spectrum of ocular manifestations in CLN2-associated batten (Jansky-Bielschowsky)
      disease correlate with advancing age and deteriorating neurological function.
AB  - BACKGROUND: Late infantile neuronal ceroid lipofuscinosis (LINCL), one form of
      Batten's disease is a progressive neurodegenerative disorder resulting from a
      CLN2 gene mutation. The spectrum of ophthalmic manifestations of LINCL and the
      relationship with neurological function has not been previously described.
      METHODS: Patients underwent ophthalmic evaluations, including anterior segment
      and dilated exams, optical coherence tomography, fluorescein and indocyanine
      green angiography. Patients were also assessed with the LINCL Neurological
      Severity Scale. Ophthalmic findings were categorized into one of five severity
      scores, and the association of the extent of ocular disease with neurological
      function was assessed. RESULTS: Fifty eyes of 25 patients were included. The mean
      age at the time of exam was 4.9 years (range 2.5 to 8.1). The mean ophthalmic
      severity score was 2.6 (range 1 to 5). The mean neurological severity score was
      6.1 (range 2 to 11). Significantly more severe ophthalmic manifestations were
      observed among older patients (p<0.005) and patients with more severe
      neurological findings (p<0.03). A direct correlation was found between the
      Ophthalmic Severity Scale and the Weill Cornell Neurological Scale (p<0.002). A
      direct association was also found between age and the ophthalmic manifestations
      (p<0.0002), with older children having more severe ophthalmic manifestations.
      CONCLUSIONS: Ophthalmic manifestations of LINCL correlate closely with the degree
      of neurological function and the age of the patient. The newly established LINCL
      Ophthalmic Scale may serve as an objective marker of LINCL severity and disease
      progression, and may be valuable in the evaluation of novel therapeutic
      strategies for LINCL, including gene therapy.

PMID- 24015293
TI  - The high cost of free tuberculosis services: patient and household costs
      associated with tuberculosis care in Ebonyi State, Nigeria.
AB  - OBJECTIVE: Poverty is both a cause and consequence of tuberculosis. The objective
      of this study is to quantify patient/household costs for an episode of
      tuberculosis (TB), its relationships with household impoverishment, and the
      strategies used to cope with the costs by TB patients in a resource-limited high
      TB/HIV setting. METHODS: A cross-sectional study was conducted in three rural
      hospitals in southeast Nigeria. Consecutive adults with newly diagnosed pulmonary
      TB were interviewed to determine the costs each incurred in their care-seeking
      pathway using a standardised questionnaire. We defined direct costs as out-of
      pocket payments, and indirect costs as lost income. RESULTS: Of 452 patients
      enrolled, majority were male 55% (249), and rural residents 79% (356), with a
      mean age of 34 (+/- 11.6) years. Median direct pre-diagnosis/diagnosis cost was
      $49 per patient. Median direct treatment cost was $36 per patient. Indirect pre
      diagnostic and treatment costs were $416, or 79% of total patient costs, $528.
      The median total cost of TB care per household was $592; corresponding to 37% of
      median annual household income pre-TB. Most patients reported having to borrow
      money 212(47%), sell assets 42(9%), or both 144(32%) to cope with the cost of
      care. Following an episode of TB, household income reduced increasing the
      proportion of households classified as poor from 54% to 79%. Before TB illness,
      independent predictors of household poverty were; rural residence (adjusted odds
      ratio [aOR] 2.8), HIV-positive status (aOR 4.8), and care-seeking at a private
      facility (aOR 5.1). After TB care, independent determinants of household poverty
      were; younger age (<= 35 years; aOR 2.4), male gender (aOR 2.1), and HIV-positive
      status (aOR 2.5). CONCLUSION: Patient and household costs for TB care are
      potentially catastrophic even where services are provided free-of-charge. There
      is an urgent need to implement strategies for TB care that are affordable for the
      poor.

PMID- 24015294
TI  - Development and validation of non-integrative, self-limited, and replicating
      minicircles for safe reporter gene imaging of cell-based therapies.
AB  - Reporter gene (RG) imaging of cell-based therapies provides a direct readout of
      therapeutic efficacy by assessing the fate of implanted cells. To permit long
      term cellular imaging, RGs are traditionally required to be integrated into the
      cellular genome. This poses a potential safety risk and regulatory bottleneck for
      clinical translation as integration can lead to cellular transformation. To
      address this issue, we have developed non-integrative, replicating minicircles
      (MCs) as an alternative platform for safer monitoring of cells in living
      subjects. We developed both plasmids and minicircles containing the
      scaffold/matrix attachment regions (S/MAR) of the human interferon-beta gene,
      driven by the CMV promoter, and expressing the bioluminescence RG firefly
      luciferase. Constructs were transfected into breast cancer cells, and expanded
      S/MAR minicircle clones showed luciferase signal for greater than 3 months in
      culture and minicircles remained as episomes. Importantly, luciferase activity in
      clonal populations was slowly lost over time and this corresponded to a loss of
      episome, providing a way to reversibly label cells. To monitor cell proliferation
      in vivo, 1.5 * 10(6) cells carrying the S/MAR minicircle were implanted
      subcutaneously into mice (n = 5) and as tumors developed significantly more
      bioluminescence signal was noted at day 35 and 43 compared to day 7 post-implant
      (p<0.05). To our knowledge, this is the first work examining the use of episomal,
      self-limited, replicating minicircles to track the proliferation of cells using
      non-invasive imaging in living subjects. Continued development of S/MAR
      minicircles will provide a broadly applicable vector platform amenable with any
      of the numerous RG technologies available to allow therapeutic cell fate to be
      assessed in individual patients, and to achieve this without the need to
      manipulate the cell's genome so that safety concerns are minimized. This will
      lead to safe tools to assess treatment response at earlier time points and
      improve the precision of cell-based therapies.

PMID- 24015295
TI  - Impact of ileocecal resection and concomitant antibiotics on the microbiome of
      the murine jejunum and colon.
AB  - Ileocecal resection (ICR) is a commonly required surgical intervention in
      unmanageable Crohn's disease and necrotizing enterocolitis. However, the impact
      of ICR, and the concomitant doses of antibiotic routinely given with ICR, on the
      intestinal commensal microbiota has not been determined. In this study, wild-type
      C57BL6 mice were subjected to ICR and concomitant single intraperitoneal
      antibiotic injection. Intestinal lumen contents were collected from jejunum and
      colon at 7, 14, and 28 days after resection and compared to non-ICR controls.
      Samples were analyzed by 16S rRNA gene pyrosequencing and quantitative PCR. The
      intestinal microbiota was altered by 7 days after ICR and accompanying antibiotic
      treatment, with decreased diversity in the colon. Phylogenetic diversity (PD)
      decreased from 11.8 +/- 1.8 in non-ICR controls to 5.9 +/- 0.5 in 7-day post-ICR
      samples. There were also minor effects in the jejunum where PD values decreased
      from 8.3 +/- 0.4 to 7.5 +/- 1.4. PCoA analysis indicated that bacterial
      populations 28 days post-ICR differed significantly from non-ICR controls.
      Moreover, colon and jejunum bacterial populations were remarkably similar 28 days
      after resection, whereas the initial communities differed markedly. Firmicutes
      and Bacteroidetes were the predominant phyla in jejunum and colon before ICR;
      however, Firmicutes became the vastly predominant phylum in jejunum and colon 28
      days after ICR. Although the microbiota returned towards a homeostatic state,
      with re-establishment of Firmicutes as the predominant phylum, we did not detect
      Bacteroidetes in the colon 28 days after ICR. In the jejunum Bacteroidetes was
      detected at a 0.01% abundance after this time period. The changes in jejunal and
      colonic microbiota induced by ICR and concomitant antibiotic injection may
      therefore be considered as potential regulators of post-surgical adaptive growth
      or function, and in a setting of active IBD, potential contributors to post
      surgical pathophysiology of disease recurrence.

PMID- 24015296
TI  - Evaluation of a novel thermosensitive heparin-poloxamer hydrogel for improving
      vascular anastomosis quality and safety in a rabbit model.
AB  - Despite progress in the design of advanced surgical techniques, stenosis recurs
      in a large percentage of vascular anastomosis. In this study, a novel heparin
      poloxamer (HP) hydrogel was designed and its effects for improving the quality
      and safety of vascular anastomosis were studied. HP copolymer was synthesized and
      its structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and
      nuclear magnetic resonance spectroscopy ((1)H-NMR). Hydrogels containing HP were
      prepared and their important characteristics related to the application in
      vascular anastomosis including gelation temperature, rheological behaviour and
      micromorphology were measured. Vascular anastomosis were performed on the right
      common carotid arteries of rabbits, and the in vivo efficiency and safety of HP
      hydrogel to achieve vascular anastomosis was verified and compared with Poloxamer
      407 hydrogel and the conventional hand-sewn method using Doppler ultrasound, CT
      angiograms, scanning electron microscopy (SEM) and histological technique. Our
      results showed that HP copolymer displayed special gel-sol-gel phase transition
      behavior with increasing temperature from 5 to 60  degrees C. HP hydrogel
      prepared from 18 wt% HP solution had a porous sponge-like structure, with
      gelation temperature at approximately 38  degrees C and maximum elastic modulus
      at 10,000 Pa. In animal studies, imaging and histological examination of rabbit
      common jugular artery confirmed that HP hydrogel group had similar equivalent
      patency, flow and burst strength as Poloxamer 407 group. Moreover, HP hydrogel
      was superior to poloxamer 407 hydrogel and hand-sewn method for restoring the
      functions and epithelial structure of the broken vessel junctions after
      operation. By combining the advantages of heparin and poloxamer 407, HP hydrogel
      holds high promise for improving vascular anastomosis quality and safety. 

PMID- 24015297
TI  - Differences in chemosensitivity between primary and metastatic tumors in
      colorectal cancer.
AB  - PURPOSE: We retrospectively evaluated the in vitro chemosensitivity of primary
      site and metastatic site tumors in colorectal cancer. METHODS: Various resected
      tumor samples (33 from lymph nodes, 42 from liver, six from lung, and 68 primary
      tumors) were assessed via a collagen gel droplet-embedded culture drug
      sensitivity test to determine chemosensitivity to a single agent or a combination
      of agents. RESULTS: Sensitivity to combination chemotherapy was significantly
      higher than that of monotherapy in the primary site group, lymph node group, and
      liver group. There was significant difference between chemosensitivity of primary
      site and that of liver metastasis in each agent (5-FU, p<0.001; SN38, p = 0.045;
      5-FU/SN38, p<0.001; OHP, p = 0.037; 5-FU/OHP, p = 0.045). CONCLUSIONS: Tumors
      showed greater in vitro chemosensitivity to combination therapy when compared
      with monotherapy. Further, tumors that had metastasized to the liver were more
      resistant to chemotherapy when compared with matched primary tumors.

PMID- 24015298
TI  - Chitin in the silk gland ducts of the spider Nephila edulis and the silkworm
      Bombyx mori.
AB  - Here we report the detection and localisation of chitin in the cuticle of the
      spinning ducts of both the spider Nephila edulis and the silkworm Bombyx mori.
      Our observations demonstrate that the duct walls of both animals contain chitin
      notwithstanding totally independent evolutionary pathways of the systems. We
      conclude that chitin may well be an essential component for the construction of
      spinning ducts; we further conclude that in both species chitin may indicate the
      evolutionary origin of the spinning ducts. 

PMID- 24015299
TI  - HER2 as a promising target for cytotoxicity T cells in human melanoma therapy.
AB  - Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of
      HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range
      of human melanoma cells including a primary culture and seven cell lines, and we
      further investigated whether HER2 could be served as a target for T cell mediated
      immunotherapy of human melanoma. Specific cytolytic activity of activated T cells
      (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against
      Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase
      reporter which did not alter HER2 expression or proliferation ability of Malme-3M
      cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed
      ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of
      1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of
      activation marker CD69 and secreted significantly higher level of IFN-gamma than
      unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti
      HER2 mAb (Herceptin(r)) or unarmed ATC, HER2Bi-armed ATC showed remarkable
      suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor
      cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the
      growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide
      a promising immunotherapy for melanoma in the future. 

PMID- 24015300
TI  - The Coxsackievirus and Adenovirus Receptor (CAR) undergoes ectodomain shedding
      and regulated intramembrane proteolysis (RIP).
AB  - The Coxsackievirus and Adenovirus Receptor (CAR) is a cell adhesion molecule
      originally characterized as a virus receptor but subsequently shown to be
      involved in physiological processes such as neuronal and heart development,
      epithelial tight junction integrity, and tumour suppression. Proteolysis of cell
      adhesion molecules and a wide variety of other cell surface proteins serves as a
      mechanism for protein turnover and, in some cases, cell signaling.
      Metalloproteases such as A Disintegrin and Metalloprotease (ADAM) family members
      cleave cell surface receptors to release their substrates' ectodomains, while the
      presenilin/gamma-secretase complex mediates regulated intramembrane proteolysis
      (RIP), releasing intracellular domain fragments from the plasma membrane. In the
      case of some substrates such as Notch and amyloid precursor protein (APP), the
      released intracellular domains enter the nucleus to modulate gene expression. We
      report that CAR ectodomain is constitutively shed from glioma cells and
      developing neurons, and is also shed when cells are treated with the phorbol
      ester phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore ionomycin.
      We identified ADAM10 as a sheddase of CAR using assays involving shRNA knockdown
      and rescue, overexpression of wild-type ADAM10 and inhibition of ADAM10 activity
      by addition of its prodomain. In vitro peptide cleavage, mass spectrometry and
      mutagenesis revealed the amino acids M224 to L227 of CAR as the site of ADAM10
      mediated ectodomain cleavage. CAR also undergoes RIP by the presenilin/gamma
      secretase complex, and the intracellular domain of CAR enters the nucleus.
      Ectodomain shedding is a prerequisite for RIP of CAR. Thus, CAR belongs to the
      increasing list of cell surface molecules that undergo ectodomain shedding and
      that are substrates for gamma-secretase-mediated RIP. 

PMID- 24015301
TI  - Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is
      partially mediated by translocation of miR-221 in microvesicles.
AB  - INTRODUCTION: microRNAs (miRs), a novel class of small non-coding RNAs, are
      involved in cell proliferation, differentiation, development, and death. In this
      study, we found that miR-221 translocation by microvesicles (MVs) plays an
      important role in cardioprotection mediated by GATA-4 overexpressed mesenchymal
      stem cells (MSC). METHODS AND RESULTS: Adult rat bone marrow MSC and neonatal rat
      ventricle cardiomyocytes (CM) were harvested as primary cultures. MSC were
      transduced with GATA-4 (MSC(GATA-4)) using the murine stem cell virus (pMSCV)
      retroviral expression system. Empty vector transfection was used as a control
      (MSC(Null)). The expression of miRs was assessed by real-time PCR and localized
      using in situ hybridization (ISH). MVs collected from MSC cultures were
      characterized by expression of CD9, CD63, and HSP70, and photographed with
      electron microscopy. Cardioprotection during hypoxia afforded by conditioned
      medium (CdM) from MSC cultures was evaluated by lactate dehydrogenase (LDH)
      release, MTS uptake by CM, and caspase 3/7 activity. Expression of miR-221/222
      was significantly higher in MSC than in CM and miR-221 was upregulated in
      MSC(GATA-4). MSC overexpression of miR-221 significantly enhanced
      cardioprotection by reducing the expression of p53 upregulated modulator of
      apoptosis (PUMA). Moreover, expression of PUMA was significantly decreased in CM
      co-cultured with MSC. MVs derived from MSC expressed high levels of miR-221, and
      were internalized quickly by CM as documented in images obtained from a Time
      Lapse Imaging System. CONCLUSIONS: Our results demonstrate that cardioprotection
      by MSC(GATA-4) may be regulated in part by a transfer of anti-apoptotic miRs
      contained within MVs.

PMID- 24015302
TI  - Locking the 150-cavity open: in silico design and verification of influenza
      neuraminidase inhibitors.
AB  - Neuraminidase (NA) of influenza is a key target for virus infection control and
      the recently discovered open 150-cavity in group-1 NA provides new opportunity
      for novel inhibitors design. In this study, we used a combination of theoretical
      methods including fragment docking, molecular linking and molecular dynamics
      simulations to design ligands that specifically target at the 150-cavity. Through
      in silico screening of a fragment compound library on the open 150-cavity of NA,
      a few best scored fragment compounds were selected to link with Zanamivir, one NA
      targeting drug. The resultant new ligands may bind both the active site and the
      150-cavity of NA simultaneously. Extensive molecular dynamics simulations in
      explicit solvent were applied to validate the binding between NA and the designed
      ligands. Moreover, two control systems, a positive control using Zanamivir and a
      negative control using a low-affinity ligand 3-(p-tolyl) allyl-Neu5Ac2en (ETT,
      abbreviation reported in the PDB) found in a recent experimental work, were
      employed to calibrate the simulation method. During the simulations, ETT was
      observed to detach from NA, on the contrary, both Zanamivir and our designed
      ligand bind NA firmly. Our study provides a prospective way to design novel
      inhibitors for controlling the spread of influenza virus. 

PMID- 24015303
TI  - The interaction of endothelin-1 and TGF-beta1 mediates vascular cell remodeling.
AB  - BACKGROUND: Pulmonary arterial hypertension is characterized by increased
      thickness of pulmonary vessel walls due to both increased proliferation of
      pulmonary arterial smooth muscle cell (PASMC) and deposition of extracellular
      matrix. In patients suffering from pulmonary arterial hypertension, endothelin-1
      (ET-1) synthesis is up-regulated and may increase PASMC activity and vessel wall
      remodeling through transforming growth factor beta-1 (TGF-beta1) and connective
      tissue growth factor. OBJECTIVE: To assess the signaling pathway leading to ET-1
      induced proliferation and extracellular matrix deposition by human PASMC.
      METHODS: PASMC were serum starved for 24 hours before stimulation with either ET
      1 and/or TGF-beta1. ET-1 was inhibited by Bosentan, ERK1/2 mitogen activated
      protein kinase (MAPK) was inhibited by U0126 and p38 MAPK was inhibited by
      SB203580. RESULTS: ET-1 increased PASMC proliferation when combined with serum.
      This effect involved the mitogen activated protein kinases (MAPK) ERK1/2 MAPK and
      was abrogated by Bosentan which caused a G1- arrest through activation of
      p27((Kip)). Regarding the contribution of extracellular matrix deposition in
      vessel wall remodeling, TGF-beta1 increased the deposition of collagen type-I and
      fibronectin, which was further increased when ET-1 was added mainly through
      ERK1/2 MAPK. In contrast, collagen type-IV was not affected by ET-1. Bosentan
      dose-dependently reduced the stimulatory effect of ET-1 on collagen type-I and
      fibronectin, but had no effect on TGF-beta1. CONCLUSION AND CLINICAL RELEVANCE:
      ET-1 alone does not induce PASMC proliferation and extracellular matrix
      deposition. However, ET-1 significantly up-regulates serum induced proliferation
      and TGF-beta1 induced extracellular matrix deposition, specifically of collagen
      type-I and fibronectin. The synergistic effects of ET-1 on serum and TGF-beta1
      involve ERK1/2 MAPK and may thus present a novel mode of action in the
      pathogenesis of pulmonary arterial hypertension.

PMID- 24015304
TI  - Experienced mindfulness meditators exhibit higher parietal-occipital EEG gamma
      activity during NREM sleep.
AB  - Over the past several years meditation practice has gained increasing attention
      as a non-pharmacological intervention to provide health related benefits, from
      promoting general wellness to alleviating the symptoms of a variety of medical
      conditions. However, the effects of meditation training on brain activity still
      need to be fully characterized. Sleep provides a unique approach to explore the
      meditation-related plastic changes in brain function. In this study we performed
      sleep high-density electroencephalographic (hdEEG) recordings in long-term
      meditators (LTM) of Buddhist meditation practices (approximately 8700 mean hours
      of life practice) and meditation naive individuals. We found that LTM had
      increased parietal-occipital EEG gamma power during NREM sleep. This increase was
      specific for the gamma range (25-40 Hz), was not related to the level of
      spontaneous arousal during NREM and was positively correlated with the length of
      lifetime daily meditation practice. Altogether, these findings indicate that
      meditation practice produces measurable changes in spontaneous brain activity,
      and suggest that EEG gamma activity during sleep represents a sensitive measure
      of the long-lasting, plastic effects of meditative training on brain function. 

PMID- 24015305
TI  - Topical gene electrotransfer to the epidermis of hairless guinea pig by non
      invasive multielectrode array.
AB  - Topical gene delivery to the epidermis has the potential to be an effective
      therapy for skin disorders, cutaneous cancers, vaccinations and systemic
      metabolic diseases. Previously, we reported on a non-invasive multielectrode
      array (MEA) that efficiently delivered plasmid DNA and enhanced expression to the
      skin of several animal models by in vivo gene electrotransfer. Here, we
      characterized plasmid DNA delivery with the MEA in a hairless guinea pig model,
      which has a similar histology and structure to human skin. Significant elevation
      of gene expression up to 4 logs was achieved with intradermal DNA administration
      followed by topical non-invasive skin gene electrotransfer. This delivery
      produced gene expression in the skin of hairless guinea pig up to 12 to 15 days.
      Gene expression was observed exclusively in the epidermis. Skin gene
      electrotransfer with the MEA resulted in only minimal and mild skin changes. A
      low level of human Factor IX was detected in the plasma of hairless guinea pig
      after gene electrotransfer with the MEA, although a significant increase of
      Factor IX was obtained in the skin of animals. These results suggest gene
      electrotransfer with the MEA can be a safe, efficient, non-invasive skin delivery
      method for skin disorders, vaccinations and potential systemic diseases where low
      levels of gene products are sufficient. 

PMID- 24015306
TI  - Effects of different pulmonary vasodilators on arterial saturation in a model of
      pulmonary hypertension.
AB  - BACKGROUND: Approved therapies for pulmonary arterial hypertension can induce
      oxygen desaturation when administered to patients with secondary forms of
      pulmonary hypertension (PH), probably due to an increase in ventilation/perfusion
      mismatch. Thus, so far these treatments have largely failed in secondary forms of
      PH. METHODS: We established an animal model of heterogeneous lung ventilation to
      evaluate the desaturation potential of mechanistically distinct vasoactive drugs
      launched or currently in clinical development for the treatment of PH. Single
      lung ventilation was induced in five groups (N = 6) of anesthetized minipigs (7
      weeks, 4 to 5 kg BW), and their hemodynamic parameters were monitored before and
      after intravenous injection of control (vehicle only), endothelin antagonist
      (bosentan; 0.3, 1, 3, 10 mg/kg), phosphodiesterase type 5 inhibitor (sildenafil;
      3, 10, 30, 100 ug/kg), and soluble guanylate cyclase stimulators (BAY 41-8543 and
      riociguat; 1, 3, 10, 30 ug/kg). Cumulative doses were administered before
      successive unilateral ventilation cycles. The doses were chosen to achieve equal
      effect on blood pressure by the different pharmacologic principles. RESULTS:
      Single-lung ventilation resulted in transient increases in mean pulmonary artery
      pressure (mPAP) and desaturation. In contrast to control, all drugs dose
      dependently decreased hypoxic mPAP (a positive treatment effect) and increased
      area under the arterial hemoglobin saturation curve (unwanted desaturation
      effect). Riociguat and bosentan reduced hypoxic mPAP to the greatest extent,
      while the soluble guanylate cyclase stimulators riociguat and BAY 41-8543 lowered
      arterial oxygen saturation of hemoglobin the least. CONCLUSIONS: Future
      investigations will be required to confirm these findings in clinical settings.

PMID- 24015307
TI  - Plasma p-cresol lowering effect of sevelamer in peritoneal dialysis patients:
      evidence from a Cross-Sectional Observational Study.
AB  - p-Cresol is a by-product of the metabolism of aromatic aminoacid operated by
      resident intestinal bacteria. In patients with chronic kidney disease, the
      accumulation of p-cresol and of its metabolite p-cresyl-sulphate causes
      endothelial dysfunction and ultimately increases the cardiovascular risk of these
      patients. Therapeutic strategies to reduce plasma p-cresol levels are highly
      demanded but not available yet. Because it has been reported that the phosphate
      binder sevelamer sequesters p-cresol in vitro we hypothesized that it could do so
      also in peritoneal dialysis patients. To explore this hypothesis we measured
      total cresol plasma concentrations in 57 patients with end-stage renal disease on
      peritoneal dialysis, 29 receiving sevelamer for the treatment of
      hyperphosphatemia and 28 patients not assuming this drug. Among the patients not
      assuming sevelamer, 16 were treated with lanthanum whereas the remaining 12
      received no drug because they were not hyperphosphatemic. Patients receiving
      sevelamer had plasma p-cresol and serum high sensitivity C-reactive protein
      concentrations significantly lower than those receiving lanthanum or no drug.
      Conversely, no difference was observed among the different groups either in
      residual glomerular filtration rate, total weekly dialysis dose, total clearance,
      urine volume, protein catabolic rate, serum albumin or serum phosphate levels.
      Multiple linear regression analysis showed that none of these variables predicted
      plasma p-cresol concentrations that, instead, negatively correlated with the use
      of sevelamer. These results suggest that sevelamer could be an effective strategy
      to lower p-cresol circulating levels in peritoneal dialysis patients in which it
      could also favorably affect cardiovascular risk because of its anti-inflammatory
      effect. 

PMID- 24015308
TI  - Two independent contributions to step variability during over-ground human
      walking.
AB  - Human walking exhibits small variations in both step length and step width, some
      of which may be related to active balance control. Lateral balance is thought to
      require integrative sensorimotor control through adjustment of step width rather
      than length, contributing to greater variability in step width. Here we propose
      that step length variations are largely explained by the typical human preference
      for step length to increase with walking speed, which itself normally exhibits
      some slow and spontaneous fluctuation. In contrast, step width variations should
      have little relation to speed if they are produced more for lateral balance. As a
      test, we examined hundreds of overground walking steps by healthy young adults (N
      = 14, age < 40 yrs.). We found that slow fluctuations in self-selected walking
      speed (2.3% coefficient of variation) could explain most of the variance in step
      length (59%, P < 0.01). The residual variability not explained by speed was small
      (1.5% coefficient of variation), suggesting that step length is actually quite
      precise if not for the slow speed fluctuations. Step width varied over faster
      time scales and was independent of speed fluctuations, with variance 4.3 times
      greater than that for step length (P < 0.01) after accounting for the speed
      effect. That difference was further magnified by walking with eyes closed, which
      appears detrimental to control of lateral balance. Humans appear to modulate fore
      aft foot placement in precise accordance with slow fluctuations in walking speed,
      whereas the variability of lateral foot placement appears more closely related to
      balance. Step variability is separable in both direction and time scale into
      balance- and speed-related components. The separation of factors not related to
      balance may reveal which aspects of walking are most critical for the nervous
      system to control. 

PMID- 24015309
TI  - Associations of tobacco use and alcohol drinking with laryngeal and
      hypopharyngeal cancer risks among men in Karunagappally, Kerala, India 
      Karunagappally cohort study.
AB  - BACKGROUND: From among a cohort of 65,553 men aged 30-84 in Karunagappally Taluk,
      Kerala, India, 52 hypopharyngeal cancer cases and 85 laryngeal cancer cases were
      identified by the Karunagappally Cancer Registry during the period between 1990
      and 2009. METHODS: We conduct Poisson regression analysis of grouped data, taking
      into account age and education. RESULTS: This study showed that the incidence
      rates of cancers of the hypopharynx and the larynx were strongly related to the
      number of bidis smoked a day (P<0.001 for both hypopharyngeal and laryngeal
      cancers) and duration of bidi smoking (P=0.009; P<0.001). Laryngeal cancer risk
      was significantly increased by bidi smoking (P<0.001), cigarette smoking
      (P=0.013) and regular alcohol use (P=0.005). CONCLUSION: The present study, the
      first cohort study to examine the association of hypopharyngeal and laryngeal
      cancer incidence rates with bidi smoking in South Asia, clearly showed dose
      response relationships between those cancer risks and bidi smoking; larger
      amounts of bidi smoked a day and longer durations of bidi smoking increased the
      incidence rates of those cancers. Tobacco chewing was found not related to the
      risk of hypopharynx or larynx cancer.

PMID- 24015310
TI  - Hemoglobin levels and weaning outcome of mechanical ventilation in difficult-to
      wean patients: a retrospective cohort study.
AB  - INTRODUCTION: The effect of hemoglobin levels on the weaning outcomes of
      mechanically ventilated patients remains under debate, particularly for the
      patients with difficult weaning. This study aims to evaluate the effect of
      hemoglobin levels on weaning outcomes in difficult-to-wean patients. METHODS:
      This retrospective cohort study was conducted in a university-affiliated teaching
      hospital in Taiwan. Patients who fulfilled the criteria of difficult weaning were
      enrolled. Medical records were reviewed to obtain data on hemograms, biochemistry
      tests, transfusion records, comorbidities and weaning outcome. The association
      between hemoglobin levels and 30-day weaning outcomes was evaluated using a
      logistic regression model. RESULTS: A total of 751 patients received mechanical
      ventilation during the study period, 138 of whom fulfilled the criteria of
      difficult weaning. Compared with the patients whose hemoglobin was <8 g/dL, those
      with higher hemoglobin levels were more likely to be successfully weaned (odds
      ratio [OR], 3.69; 95% CI, 1.22-11.15 for hemoglobin 8-10 g/dL and OR, 4.16, 95%
      CI, 1.30-13.29 for hemoglobin >10 g/dL). Multivariate analysis showed that the
      odds ratio for weaning success remained significant for hemoglobin levels of 8-10
      g/dL (adjusted OR, 3.3; 95% CI, 1.07-10.15) with borderline significance for
      hemoglobin level > 10 g/dL (adjusted OR, 2.95, 95% CI, 0.88-9.96). CONCLUSIONS:
      Hemoglobin level is independently associated with weaning outcome in difficult-to
      wean patients. Further studies are needed to evaluate whether a restrictive
      transfusion trigger for acute critical illness is also appropriate for such
      patients.

PMID- 24015312
TI  - Joint effects of asymmetric payoff and reciprocity mechanisms on collective
      cooperation in water sharing interactions: a game theoretic perspective.
AB  - Common-pool resource (CPR) dilemmas distinguish themselves from general public
      good problems by encompassing both social and physical features. This paper
      examines how a physical mechanism, namely asymmetric payoff; and a social
      mechanism, reciprocity; simultaneously affect collective cooperation in
      theoretical water sharing interactions. We present an iterative N-person game
      theoretic model to investigate the joint effects of these two mechanisms in a
      linear fully connected river system under three information assumptions. From a
      simple evolutionary perspective, this paper quantitatively addresses the
      conditions for Nash Equilibrium in which collective cooperation might be
      established. The results suggest that direct reciprocity increases every actor's
      motivation to contribute to the collective good of the river system. Meanwhile,
      various upstream and downstream actors manifest individual disparities as a
      result of the direct reciprocity and asymmetric payoff mechanisms. More
      specifically, the downstream actors are less willing to cooperate unless there is
      a high probability that long-term interactions are ensured; however, a greater
      level of asymmetries is likely to increase upstream actors' incentives to
      cooperate even though the interactions could quickly end. The upstream actors
      also display weak sensitivity to an increase in the total number of actors, which
      generally results in a reduction in the other actors' motivation for cooperation.
      It is also shown that the indirect reciprocity mechanism relaxes the overall
      conditions for cooperative Nash Equilibrium. 

PMID- 24015313
TI  - Newcastle disease virus fusion protein is the major contributor to protective
      immunity of genotype-matched vaccine.
AB  - Virulent strains of Newcastle disease virus (NDV) can cause devastating disease
      in chickens worldwide. Although the current vaccines are substantially effective,
      they do not completely prevent infection, virus shedding and disease. To produce
      genotype-matched vaccines, a full-genome reverse genetics system has been used to
      generate a recombinant virus in which the F protein cleavage site has been
      changed to that of avirulent vaccine virus. In the other strategy, the vaccines
      have been generated by replacing the F and HN genes of a commercial vaccine
      strain with those from a genotype-matched virus. However, the protective efficacy
      of a chimeric virus vaccine has not been directly compared with that of a full
      genome virus vaccine developed by reverse genetics. Therefore, in this study, we
      evaluated the protective efficacy of genotype VII matched chimeric vaccines by
      generating three recombinant viruses based on avirulent LaSota (genotype II)
      strain in which the open reading frames (ORFs) encoding the F and HN proteins
      were replaced, individually or together, with those of the circulating and highly
      virulent Indonesian NDV strain Ban/010. The cleavage site of the Ban/010 F
      protein was mutated to the avirulent motif found in strain LaSota. In vitro
      growth characteristics and a pathogenicity test indicated that all three chimeric
      viruses retained the highly attenuated phenotype of the parental viruses.
      Immunization of chickens with chimeric and full-length genome VII vaccines
      followed by challenge with virulent Ban/010 or Texas GB (genotype II) virus
      demonstrated protection against clinical disease and death. However, only those
      chickens immunized with chimeric rLaSota expressing the F or F plus HN proteins
      of the Indonesian strain were efficiently protected against shedding of Ban/010
      virus. Our findings showed that genotype-matched vaccines can provide protection
      to chickens by efficiently preventing spread of virus, primarily due to the F
      protein. 

PMID- 24015311
TI  - Increased risk of Q151M and K65R mutations in patients failing stavudine
      containing first-line antiretroviral therapy in Cambodia.
AB  - BACKGROUND: Multi-nucleos(t)ide resistance (MNR) mutations including Q151M, K65R
      mutations, and insertion at codon 69 of HIV-1 reverse transcriptase coding region
      may confer resistance to all molecules of nucleos(t)ide reverse transcriptase
      inhibitors (NRTI). The presence of these mutations is an emerging problem
      compromising non-nucleoside reverse transcriptase inhibitors and protease
      inhibitors-based therapies. Furthermore, factors associated with selection of
      these mutations are still not well defined. The current study aimed to evaluate
      the frequency and to characterize factors associated with the occurrence of multi
      nucleos(t)ide resistance mutations among HIV-1 infected patients failing
      recommended first-line antiretroviral regimens in Cambodia. METHODOLOGY/PRINCIPAL
      FINDING: This is a retrospective analysis of HIV-1 drug resistance genotyping of
      520 HIV-1 infected patients in virological failure (viral load > 250 copies/mL)
      while on first-line antiretroviral therapy in Cambodia with at least one reverse
      transcriptase inhibitor resistance associated mutation. Among these 520 patients,
      a total of 66 subjects (66/520, 12.7%) presented >= 1 MNR mutation, including
      Q151M, K65R, and Insert69 for 59 (11.3%), 29 (5.6%), and 2 (0.4%) patients,
      respectively. In multivariate analysis, both Q151M (p = 0.039) and K65R (p =
      0.029) mutations were independently associated with current stavudine- compared
      to zidovudine-use. CONCLUSION: Such selection of mutations by stavudine
      drastically limits the choice of antiretroviral molecules available for second
      line therapy in resource-limited settings. This finding supports the World Health
      Organization's recommendation for stavudine phase-out.

PMID- 24015314
TI  - Sulfated Escherichia coli K5 polysaccharide derivatives inhibit dengue virus
      infection of human microvascular endothelial cells by interacting with the viral
      envelope protein E domain III.
AB  - Dengue virus (DENV) is an emerging mosquito-borne pathogen that causes cytokine
      mediated alterations in the barrier function of the microvascular endothelium,
      leading to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). We
      observed that DENV (serotype 2) productively infects primary (HMVEC-d) and
      immortalized (HMEC-1) human dermal microvascular endothelial cells, despite the
      absence of well-described DENV receptors, such as dendritic cell-specific
      intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) or the mannose
      receptor on the cell surface. However, heparan sulfate proteoglycans (HSPGs) were
      highly expressed on these cells and pre-treatment of HMEC-1 cells with heparinase
      II or with glycosaminoglycans reduced DENV infectivity up to 90%, suggesting that
      DENV uses HSPGs as attachment receptor on microvascular endothelial cells.
      Sulfated Escherichia coli K5 derivatives, which are structurally similar to
      heparin/heparan sulfate but lack anticoagulant activity, were able to block DENV
      infection of HMEC-1 and HMVEC-d cells in the nanomolar range. The highly sulfated
      K5-OS(H) and K5-N,OS(H) inhibited virus attachment and subsequent entry into
      microvascular endothelial cells by interacting with the viral envelope (E)
      protein, as shown by surface plasmon resonance (SPR) analysis using the receptor
      binding domain III of the E protein. 

PMID- 24015315
TI  - Structural interactions within the default mode network identified by Bayesian
      network analysis in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a well-known neurodegenerative disease that is
      associated with dramatic morphological abnormalities. The default mode network
      (DMN) is one of the most frequently studied resting-state networks. However, less
      is known about specific structural dependency or interactions among brain regions
      within the DMN in AD. In this study, we performed a Bayesian network (BN)
      analysis based on regional grey matter volumes to identify differences in
      structural interactions among core DMN regions in structural MRI data from 80 AD
      patients and 101 normal controls (NC). Compared to NC, the structural
      interactions between the medial prefrontal cortex (mPFC) and other brain regions,
      including the left inferior parietal cortex (IPC), the left inferior temporal
      cortex (ITC) and the right hippocampus (HP), were significantly reduced in the AD
      group. In addition, the AD group showed prominent increases in structural
      interactions from the left ITC to the left HP, the left HP to the right ITC, the
      right HP to the right ITC, and the right IPC to the posterior cingulate cortex
      (PCC). The BN models significantly distinguished AD patients from NC with 87.12%
      specificity and 81.25% sensitivity. We then used the derived BN models to examine
      the replicability and stability of AD-associated BN models in an independent
      dataset and the results indicated discriminability with 83.64% specificity and
      80.49% sensitivity. The results revealed that the BN analysis was effective for
      characterising regional structure interactions and the AD-related BN models could
      be considered as valid and predictive structural brain biomarker models for AD.
      Therefore, our study can assist in further understanding the pathological
      mechanism of AD, based on the view of the structural network, and may provide new
      insights into classification and clinical application in the study of AD in the
      future. 

PMID- 24015316
TI  - Host targeted activity of pyrazinamide in Mycobacterium tuberculosis infection.
AB  - Pyrazinamide (PZA) is one of the first line antibiotics used for the treatment of
      tuberculosis (TB). In the present study, we have used in vitro and in vivo
      systems to investigate whether PZA, in addition to its known anti-mycobacterial
      properties, modulate the host immune response during Mycobacterium tuberculosis
      (Mtb) infection. In vitro we have examined the effect of PZA on cytokine and
      chemokine release by Mtb-infected or Toll-like receptor (TLR) -stimulated primary
      human monocytes. In vivo, we have investigated at the transcriptional levels
      using genome-wide microarray gene expression analysis, whether PZA treatment of
      Mtb-infected mice alters the host immune response to Mtb infection in the lungs.
      Here, we report that PZA treatment of Mtb-infected human monocytes and mice
      significantly reduces the release of pro-inflammatory cytokines and chemokines,
      including IL-1beta, IL-6, TNF-alpha and MCP-1 at the protein and at the gene
      transcription levels, respectively. Data from microarray analysis also reveal
      that PZA treatment of Mtb-infected mice significantly alters the expression level
      of genes involved in the regulation of the pro-inflammatory mediators, lung
      inflammatory response and TLR signaling networks. Specifically, genes coding for
      adenylate cyclase and Peroxisome-Proliferator Activated Receptor (PPAR),
      molecules known for their anti-inflammatory effect, were found to be up-regulated
      in the lungs of PZA-treated Mtb-infected mice. Based on the microarray findings,
      we propose that PZA treatment modulates the host immune response to Mtb infection
      by reducing pro-inflammatory cytokine production, probably through PPAR- and NF
      kB- dependent pathways. In addition, our results suggest that inclusion or
      exclusion of PZA in the TB treatment regimen could potentially affect the
      biomarker signature detected in the circulation of TB patients. 

PMID- 24015317
TI  - Cylindrospermopsin and saxitoxin synthetase genes in Cylindrospermopsis
      raciborskii strains from Brazilian freshwater.
AB  - The Cylindrospermopsis raciborskii population from Brazilian freshwater is known
      to produce saxitoxin derivatives (STX), while cylindrospermopsin (CYN), which is
      commonly detected in isolates from Australia and Asia continents, has thus far
      not been detected in South American strains. However, during the investigation
      for the presence of cyrA, cyrB, cyrC and cyrJ CYN synthetase genes in the genomes
      of four laboratory-cultured C. raciborskii Brazilian strains, the almost complete
      cyrA gene sequences were obtained for all strains, while cyrB and cyrC gene
      fragments were observed in two strains. These nucleotide sequences were
      translated into amino acids, and the predicted protein functions and domains
      confirmed their identity as CYN synthetase genes. Attempts to PCR amplify cyrJ
      gene fragments from the four strains were unsuccessful. Phylogenetic analysis
      grouped the nucleotide sequences together with their homologues found in known
      CYN synthetase clusters of C. raciborskii strains with high bootstrap support. In
      addition, fragments of sxtA, sxtB and sxtI genes involved in STX production were
      also obtained. Extensive LC-MS analyses were unable to detect CYN in the cultured
      strains, whereas the production of STX and its analogues was confirmed in
      CENA302, CENA305 and T3. To our knowledge, this is the first study reporting the
      presence of cyr genes in South American strains of C. raciborskii and the
      presence of sxt and cyr genes in a single C. raciborskii strain. This discovery
      suggests a shift in the type of cyanotoxin production over time of South American
      strains of C. raciborskii and contributes to the reconstruction of the
      evolutionary history and diversification of cyanobacterial toxins. 

PMID- 24015319
TI  - Anthrax edema factor toxicity is strongly mediated by the N-end rule.
AB  - Anthrax edema factor (EF) is a calmodulin-dependent adenylate cyclase that
      converts adenosine triphosphate (ATP) into 3'-5'-cyclic adenosine monophosphate
      (cAMP), contributing to the establishment of Bacillus anthracis infections and
      the resulting pathophysiology. We show that EF adenylate cyclase toxin activity
      is strongly mediated by the N-end rule, and thus is dependent on the identity of
      the N-terminal amino acid. EF variants having different N-terminal residues
      varied by more than 100-fold in potency in cultured cells and mice. EF variants
      having unfavorable, destabilizing N-terminal residues showed much greater
      activity in cells when the E1 ubiquitin ligase was inactivated or when proteasome
      inhibitors were present. Taken together, these results show that EF is uniquely
      affected by ubiquitination and/or proteasomal degradation. 

PMID- 24015318
TI  - Deletion of hepatic FoxO1/3/4 genes in mice significantly impacts on glucose
      metabolism through downregulation of gluconeogenesis and upregulation of
      glycolysis.
AB  - Forkhead transcription factors FoxO1/3/4 have pleiotrophic functions including
      anti-oxidative stress and metabolism. With regard to glucose metabolism, most
      studies have been focused on FoxO1. To further investigate their hepatic
      functions, we generated liver-specific FoxO1/3/4 knockout mice (LTKO) and
      examined their collective impacts on glucose homeostasis under physiological and
      pathological conditions. As compared to wild-type mice, LTKO mice had lower blood
      glucose levels under both fasting and non-fasting conditions and they manifested
      better glucose and pyruvate tolerance on regular chow diet. After challenged by a
      high-fat diet, wild-type mice developed type 2 diabetes, but LTKO mice remained
      euglycemic and insulin-sensitive. To understand the underlying mechanisms, we
      examined the roles of SIRT6 (Sirtuin 6) and Gck (glucokinase) in the FoxO
      mediated glucose metabolism. Interestingly, ectopic expression of SIRT6 in the
      liver only reduced gluconeogenesis in wild-type but not LTKO mice whereas
      knockdown of Gck caused glucose intolerance in both wild-type and LTKO mice. The
      data suggest that both decreased gluconeogenesis and increased glycolysis may
      contribute to the overall glucose phenotype in the LTKO mice. Collectively,
      FoxO1/3/4 transcription factors play important roles in hepatic glucose
      homeostasis. 

PMID- 24015320
TI  - Identification of amino acid residues of ERH required for its recruitment to
      nuclear speckles and replication foci in HeLa cells.
AB  - ERH is a small, highly evolutionarily conserved nuclear protein of unknown
      function. Its three-dimensional structure is absolutely unique and it can form a
      homodimer through a beta sheet surface. ERH has been shown to interact, among
      others, with PDIP46/SKAR and Ciz1. When coexpressed with the latter protein, ERH
      accumulates in replication foci in the nucleus of HeLa cells. Here, we report
      that when ERH is coexpressed with PDIP46/SKAR in HeLa cells, it is recruited to
      nuclear speckles, and identify amino acid residues critical for targeting ERH to
      both these subnuclear structures. ERH H3A Q9A shows a diminished recruitment to
      nuclear speckles but it is recruited to replication foci. ERH E37A T51A is very
      poorly recruited to replication foci while still accumulating in nuclear
      speckles. Consequently, ERH H3A Q9A E37A T51A is recruited neither to nuclear
      speckles nor to replication foci. The lack of interactions of these three ERH
      forms with PDIP46/SKAR and/or Ciz1 was further confirmed in vitro by GST pull
      down assay. The residues whose substitutions interfere with the accumulation in
      nuclear speckles are situated on the beta sheet surface of ERH, indicating that
      only the monomer of ERH can interact with PDIP46/SKAR. Substitutions affecting
      the recruitment to replication foci map to the other side of ERH, near a long
      loop between the alpha1 and alpha2 helices, thus both the monomer and the dimer
      of ERH could interact with Ciz1. The construction of the ERH mutants not
      recruited to nuclear speckles or replication foci will facilitate further studies
      on ERH actions in these subnuclear structures. 

PMID- 24015322
TI  - CASE REPORT Rotational Vascularized Tibiaplasty After Oncologic Resection and
      Major Wound Healing Problems: A Novel Technique.
AB  - OBJECTIVE: To describe a novel method to reconstruct, with a vascularized
      rotational tibiaplasty, a complex femoral defect in an adolescent. METHODS: After
      a femoral osteosarcoma resection, allograft reconstruction, and chemotherapy, an
      11-year-old girl developed recurrent thigh wound infections and femoral allograft
      osteomyelitis despite multiple operative interventions. At the age of 13, she
      presented to our center with a complex right thigh wound and an unstable lower
      extremity secondary to a segmental femoral loss. To reestablish thigh stability
      and function and to avoid amputation at the hip, the authors performed a
      rotational vascularized tibiaplasty. The tibia was rotated 180 degrees  with the
      pivot at the knee. The distal tibia was internally stabilized to the residual
      proximal femur. RESULTS: Ten years later, the patient had a stable thigh, a
      functional hip, no evidence of infection or sarcoma, and a Toronto Extremity
      Salvage Score of 92.5 (minimal disability). CONCLUSIONS: In this patient, the
      tibial rotationplasty provided a vascularized bone strut mimicking the resected
      femur; saved the hip; obviated an allograft bone; and created a functional,
      biologic, stable, and durable thigh that allowed full weight bearing on a
      prosthesis, with a low physical disability level. We conclude that, for patients
      with complex femoral defects, a vascularized rotational tibiaplasty should be
      considered a feasible option before amputation.

PMID- 24015323
TI  - Locally aggressive and multicentric recurrent extraocular sebaceous carcinoma:
      case report and literature review.
AB  - OBJECTIVE: Sebaceous Carcinoma is a rare and aggressive malignant tumor. We
      present a case report of a large truncal tumor with multicentricity and
      aggressive locoregional recurrence that required trapezius myocutaneous flap
      reconstruction. Examining patterns of multicentricity, metastasis, and recurrence
      of sebaceous carcinoma in the literature we sought to explore potential reasons
      behind the aggressive behavior. METHODS: Retrospective chart review was used to
      analyze the case in detail. Preoperative workup, intraoperative details,
      pathology, and follow-up visits were reviewed. Selected literature was considered
      with series of 5 or more patients. RESULTS: The recurrent tumor was resected with
      negative margins leaving a defect of 14 * 7 cm(2) that was covered with a
      trapezius myocutaneous flap. Postoperative hospital course was uneventful with no
      further local recurrence. On follow-up visits, tumors at other sites have been
      discovered. Reported rates of multicentricity, metastasis, and recurrence vary
      widely in the literature, but both subtypes of sebaceous carcinoma behave
      aggressively. CONCLUSIONS: A combination of genetic predisposition, delayed
      definitive care, and inherent tumor biology led to the aggressive locoregional
      disease in this case.

PMID- 24015321
TI  - Signatures of rapid evolution in urban and rural transcriptomes of white-footed
      mice (Peromyscus leucopus) in the New York metropolitan area.
AB  - Urbanization is a major cause of ecological degradation around the world, and
      human settlement in large cities is accelerating. New York City (NYC) is one of
      the oldest and most urbanized cities in North America, but still maintains 20%
      vegetation cover and substantial populations of some native wildlife. The white
      footed mouse, Peromyscusleucopus, is a common resident of NYC's forest fragments
      and an emerging model system for examining the evolutionary consequences of
      urbanization. In this study, we developed transcriptomic resources for urban P.
      leucopus to examine evolutionary changes in protein-coding regions for an
      exemplar "urban adapter." We used Roche 454 GS FLX+ high throughput sequencing to
      derive transcriptomes from multiple tissues from individuals across both urban
      and rural populations. From these data, we identified 31,015 SNPs and several
      candidate genes potentially experiencing positive selection in urban populations
      of P. leucopus. These candidate genes are involved in xenobiotic metabolism,
      innate immune response, demethylation activity, and other important biological
      phenomena in novel urban environments. This study is one of the first to report
      candidate genes exhibiting signatures of directional selection in divergent urban
      ecosystems. 

PMID- 24015324
TI  - FREQUENCY CONTENT OF CARTILAGE IMPACT FORCE SIGNAL REFLECTS ACUTE HISTOLOGIC
      STRUCTURAL DAMAGE.
AB  - OBJECTIVE: The objective of this study was to determine if acute cartilage impact
      damage could be predicted by a quantification of the frequency content of the
      impact force signal. DESIGN: Osteochondral specimens excised from bovine lateral
      tibial plateaus were impacted with one of six impact energies. Each impact force
      signal underwent frequency analysis, with the amount of higher-frequency content
      (percent of frequency spectrum above 1 KHz) being registered. Specimens were
      histologically evaluated to assess acute structural damage (articular surface
      cracking and cartilage crushing) resulting from the impact. RESULTS: Acute
      histologic structural damage to the cartilage had higher concordance with the
      high-frequency content measure than with other mechanical impact measures
      (delivered impact energy, impact maximum stress, and impact maximum stress rate
      of change). CONCLUSIONS: This result suggests that the frequency content of an
      impact force signal, specifically the proportion of higher-frequency components,
      can be used as a quick surrogate measure for acute structural cartilage injury.
      Taking advantage of this relationship could reduce the time and expense of
      histological processing needed to morphologically assess cartilage damage,
      especially for purposes of initial screening when evaluating new impaction
      protocols.

PMID- 24015325
TI  - Desmethyl Macrolides: Synthesis and Evaluation of 4,8-Didesmethyl Telithromycin.
AB  - There is an urgent need for novel sources of antibiotics to address the incessant
      and inevitable onset of bacterial resistance. To this end, we have initiated a
      structure-based drug design program that features a desmethylation strategy
      (i.e., replacing methyl groups with hydrogens). Herein we report the total
      synthesis, molecular modeling and biological evaluation of 4,8-didesmethyl
      telithromycin (5), a novel desmethyl analogue of the third-generation ketolide
      antibiotic telithromycin (2), which is an FDA-approved semisynthetic derivative
      of erythromycin (1). We found 4,8-didesmethyl telithromycin (5) to be eight times
      more active than previously prepared 4,8,10-tridesmethyl congener (3) and two
      times more active than 4,10-didesmethyl regioisomer (4) in MIC assays. While less
      potent than telithromycin (2) and paralleling the observations made in the
      previous study of 4,10-didesmethyl analogue (4), the inclusion of a single methyl
      group improves biological activity thus supporting its role in antibiotic
      activity.

PMID- 24015326
TI  - Adenosine Dioxolane Nucleoside Phosphoramidates as Antiviral Agents for Human
      Immunodeficiency and Hepatitis B Viruses.
AB  - There are currently six nucleoside reverse transcriptase inhibitors (NRTI) that
      are FDA approved for human clinical use and these remain the backbone of current
      HIV therapy. In order for these NRTIs to be effective they need to be
      phosphorylated consecutively by cellular kinases to their triphosphate forms.
      Herein, we report the synthesis of C-6 modified (-)-beta-D-(2R,4R)-1,3-dioxolane
      adenosine nucleosides and their nucleotides including our novel phosphoramidate
      prodrug technology. We have introduced a side chain moiety on the phenol portion
      of the phosphoramidate to reduce the toxicity potential. The synthesized
      phosphoramidates displayed up to a 3,600-fold greater potency versus HIV-1 when
      compared to their corresponding parent nucleoside and were up to 300-fold more
      potent versus HBV. No cytotoxicity was observed up to 100 MUM in the various cell
      systems tested, except for compound 17 and 18 which displayed a CC50 of 7.3 and
      12 MUM respectively in Huh-7 cells. The improved and significant dual antiviral
      activity of these novel phosphoramidate nucleosides was partially explained by
      the increased intracellular formation of the adenosine dioxolane triphosphate.

PMID- 24015327
TI  - Development of a chimeric c-Src kinase and HDAC inhibitor.
AB  - On the basis of synergism observed between a selective c-Src kinase inhibitor
      with an HDAC inhibitor, the development of the first chimeric c-Src kinase and
      HDAC inhibitor is described. The optimized chimeric inhibitor is shown to be a
      potent c-Src and HDAC inhibitor. Chimeric inhibitor 4 is further shown to be
      highly efficacious in cancer cell lines and significantly more efficacious than a
      dual-targeting strategy using discrete c-Src and HDAC inhibitors.

PMID- 24015328
TI  - The first Keystone Symposia Conference on pulmonary vascular isease and right
      ventricular dysfunction: Current concepts and future therapies.

PMID- 24015329
TI  - Signal transduction in the development of pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a unique disease. Properly speaking, it
      is not a disease of the lung. It can be seen more as a microvascular disease
      occurring mainly in the lungs and affecting the heart. At the cellular level, the
      PAH paradigm is characterized by inflammation, vascular tone imbalance, pulmonary
      arterial smooth muscle cell proliferation and resistance to apoptosis and the
      presence of in situ thrombosis. At a clinical level, the aforementioned abnormal
      vascular properties alter physically the pulmonary circulation and ventilation,
      which greatly influence the right ventricle function as it highly correlates with
      disease severity. Consequently, right heart failure remains the principal cause
      of death within this cohort of patients. While current treatment modestly improve
      patients' conditions, none of them are curative and, as of today, new therapies
      are lacking. However, the future holds potential new therapies that might have
      positive influence on the quality of life of the patient. This article will first
      review the clinical presentation of the disease and the different molecular
      pathways implicated in the pathobiology of PAH. The second part will review
      tomorrow's future putative therapies for PAH. 

PMID- 24015330
TI  - Gender, sex hormones and pulmonary hypertension.
AB  - Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a
      greater susceptibility to disease among females, although females with PAH appear
      to live longer after diagnosis. While this "estrogen paradoxo of enhanced female
      survival despite increased female susceptibility remains a mystery, recent
      progress has begun to shed light upon the interplay of sex hormones, the
      pathogenesis of pulmonary hypertension, and the right ventricular response to
      stress. For example, emerging data in humans and experimental models suggest that
      estrogens or differential sex hormone metabolism may modify disease risk among
      susceptible subjects, and that estrogens may interact with additional local
      factors such as serotonin to enhance the potentially damaging chronic effects of
      estrogens on the pulmonary vasculature. Regardless, it remains unclear why not
      all estrogenic compounds behave equally, nor why estrogens appear to be
      protective in certain settings but detrimental in others. The contribution of
      androgens and other compounds, such as dehydroepiandrosterone, to pathogenesis
      and possibly treatment must be considered as well. In this review, we will
      discuss the recent understandings on how estrogens, estrogen metabolism,
      dehydroepiandrosterone, and additional susceptibility factors may all contribute
      to the pathogenesis or potentially to the treatment of pulmonary hypertension, by
      evaluating current human, cell-based, and experimental model data. 

PMID- 24015332
TI  - On the origin of microparticles: From "platelet dust" to mediators of
      intercellular communication.
AB  - Microparticles are submicron vesicles shed from a variety of cells. Peter Wolf
      first identified microparticles in the midst of ongoing blood coagulation
      research in 1967 as a product of platelets. He termed them platelet dust.
      Although initially thought to be useless cellular trash, decades of research
      focused on the tiny vesicles have defined their roles as participators in
      coagulation, cellular signaling, vascular injury, and homeostasis. The purpose of
      this review is to highlight the science leading up to the discovery of
      microparticles, feature discoveries made by key contributors to the field of
      microparticle research, and discuss their positive and negative impact on the
      pulmonary circulation. 

PMID- 24015333
TI  - Chronic thromboembolic pulmonary hypertension: Medical treatment.
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is responsible for
      significant levels of morbidity and mortality. The estimated cumulative incidence
      of CTEPH is 2-4% among patients presenting with acute pulmonary thromboembolism.
      Currently, at the time of CTEPH diagnosis, 37.9% of the patients in an
      international registry were receiving at least one pulmonary arterial
      hypertension (PAH)-targeted therapy. Advanced medical therapy is considered in
      patients with inoperable disease, as a bridge to pulmonary endarterectomy or in
      those with persistent or recurrent pulmonary hypertension. PAH-specific medical
      therapies include endothelin receptor antagonists, phosphodiesterase inhibitors,
      and prostacyclin analogues. The present article will focus on recent developments
      in the pharmacological treatment of CTEPH. 

PMID- 24015331
TI  - Role of microRNAs in lung development and pulmonary diseases.
AB  - MicroRNAs (miRNAs) are a class of small noncoding RNA which exert post
      transcriptional gene regulation activity by targeting messenger RNAs. miRNAs have
      been found to be involved in various fundamental biological processes and
      deregulation of miRNAs is known to result in pathological conditions. In this
      review, we provide an overview of recent discoveries on the role played by this
      class of molecules in lung development and in pulmonary diseases, such as asthma,
      cystic fibrosis, chronic obstructive pulmonary disease, and pulmonary artery
      hypertension. Considering the relevant role of these miRNAs under physiological
      and pathological conditions, they represent new clinical targets as well as
      diagnostic and prognostic tools. Therefore, this review pays special attention to
      recent advances and possible future directions for the use of miRNAs for clinical
      applications. 

PMID- 24015334
TI  - Reproducibility of intracardiac and transpulmonary biomarkers in the evaluation
      of pulmonary hypertension.
AB  - Intracardiac and transpulmonary levels of natriuretic peptides (NPs) and cyclic
      guanosine monophosphate (cGMP) provide insight into the pathophysiology of
      pulmonary hypertension (PH) secondary to left-heart failure but have not been
      evaluated in established or suspected pulmonary arterial hypertension (PAH).
      Demonstrating adequate reproducibility of these markers is an important precursor
      to further study. We hypothesized that the reproducibility of intracardiac and
      transpulmonary NPs and cGMP is similar to the reproducibility of these markers
      sampled from the peripheral venous circulation. In outpatients undergoing right
      heart catheterization for PH, blood samples were obtained from a peripheral
      venous site, superior vena cava, inferior vena cava, coronary sinus, pulmonary
      artery, and pulmonary capillary wedge position. At each site, a repeat sample was
      collected approximately 60 seconds after the initial measurement. Reproducibility
      was assessed using the slope of the regression line between initial and follow-up
      levels. We enrolled 10 patients: Six had PAH, two had pulmonary venous
      hypertension, and two had normal pulmonary pressure. At all sites, the slopes of
      the regression lines for BNP were close to identity. BNP was generally more
      reproducible than NT-pro-BNP. For the NPs and cGMP, reproducibility at
      intracardiac and transpulmonary sites was similar to the peripheral venous site.
      Reproducibility of NPs was not influenced by PH severity, access site, or time
      between measurements. The two patients with the highest transpulmonary pressure
      gradients had high transpulmonary BNP uptake, but their transpulmonary cGMP
      gradients were negative. In patients evaluated for PH, reproducibility of NPs and
      cGMP at intracardiac and transpulmonary sites is high and is comparable to that
      of peripheral venous measurements. 

PMID- 24015335
TI  - Magnetic resonance imaging of the right ventricle in pediatric pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) causes changes in the right ventricle (RV),
      affecting RV size and function, ultimately leading to death. These changes have
      been evaluated by cardiac MRI (CMR) in adults with PAH, but not in children.
      Using CMR in pediatric patients with PAH, we examined how RV size and function
      (1) compare to normal data, (2) change over time, and (3) compare to similar
      studies in the adult population. Data from two institutions were retrospectively
      reviewed. Subjects with PAH and a CMR were included. Baseline CMR variables
      (right and left ventricular end-diastolic and end-systolic volumes indexed for
      body surface area, and calculated stroke volume and ejection fraction) were
      compared to normative data and follow-up CMR data. Twenty-six subjects (15
      female), age 2-16 (mean 11) years, with idiopathic PAH were included. All
      patients were on PAH medication, and 65% on prostacyclin therapy. The baseline 6
      Minute Walk Distance (6MWD; 481 +/- 137) was normal. RV volumes and ejection
      fraction were markedly abnormal compared to normal data (P < 0.001). Follow-up
      CMRs were analyzed in 15 patients. RV volumes and function and LV stroke volume
      showed no significant change over one year. Our pediatric patients with PAH have
      markedly abnormal right ventricles by CMR but have normal walk distances. The
      lack of change in CMR parameters over one year may represent a stable cohort and
      is different than similar studies in adults. 

PMID- 24015336
TI  - Schistosomiasis causes remodeling of pulmonary vessels in the lung in a
      heterogeneous localized manner: Detailed study.
AB  - Schistosomiasis is a global parasitic disease with high impact on public health
      in tropical areas. Schistosomiasis is a well-described cause of pulmonary
      arterial hypertension (PAH). The exact pathogenesis is still unclear, though
      inflammatory mechanisms are suspected. Another unknown is whether the changes in
      the pulmonary vasculature are generalized or localized. We studied 13 mice
      infected with cercariae for 12 weeks compared with 10 control mice. In our model,
      we observed that the liver was a target during infection and was enlarged more
      than two-fold after infection. However, right heart hypertrophy as measured by
      RV/(LV + S) ratio was not observed at this time point. Moreover, we noticed that
      72% of the sampled lobes (92% of the lungs) harvested from these animals
      costained evidence of granulomatous changes, secondary to egg deposition. We
      systemically mapped the distribution of granulomatous lesions in right lung lobes
      (n = 43) of infected mice. We observed that the distribution of the granulomatous
      lesions was heterogeneous. Remodeled pulmonary vessels were seen in 26% of the
      lobes (46% of the lungs) and were observed only in close proximity to the
      granuloma. No remodeling was observed in the absence of granulomas. These
      findings support the view that pulmonary vascular remodeling is caused by the
      local presence of granulomas in PAH associated with schistosomiasis. The
      heterogeneous nature of the remodeling partly explains why many patients with
      schistosomiasis do not develop pulmonary hypertension. 

PMID- 24015337
TI  - Increased pulmonary artery diameter on chest computed tomography can predict
      borderline pulmonary hypertension.
AB  - Pulmonary hypertension (PH) often leads to dilatation of the pulmonary artery
      (PA), which can be measured on chest computed tomography (CT). While the
      predictive capability of PA dilatation is useful to distinguish PH (mean PA
      pressure >=25 mmHg) from normal (mean PA pressure <= 20 mmHg), CT characteristics
      of borderline PH (mean PA pressure 21-24 mmHg) have not been described. We aimed
      to investigate whether patients with borderline PH already show PA dilatation and
      to assess the diagnostic accuracy of PA dilatation for borderline PH diagnosis.
      Between April 2003 and September 2008, consecutive symptomatic patients with a
      mean PA pressure below 25 mmHg on right heart catheterization who had a chest CT
      available were retrospectively included. PA diameters from chest CT were
      correlated with hemodynamic measurements and analyzed with respect to their
      accuracy of predicting borderline PH. Main PA diameters were significantly larger
      in 26 patients with borderline PH compared with 52 patients without PH (3.16 +/-
      0.53 vs. 2.78 +/- 0.43 cm, P = 0.001). The main PA diameter on CT correlated with
      mean PA pressure (r = 0.496, P < 0.001) and pulmonary vascular resistance (r =
      0.445, P < 0.001), and predicted borderline PH with sensitivity, specificity,
      negative and positive predictive values of 77%, 62%, 84%, and 50%, respectively,
      using a cutoff >=2.9 cm. This first systematic investigation of CT parameters in
      symptomatic patients with mean PA pressures less than 25 mmHg could show that,
      even in patients with borderline PH, significant PA dilatation can be present,
      which was related to PA pressure and pulmonary vascular resistance. This can be
      useful for identification of patients with borderline PH for further study and to
      prompt further diagnostic work-up of possible underlying diseases. 

PMID- 24015338
TI  - Circulating angiogenic modulatory factors predict survival and functional class
      in pulmonary arterial hypertension.
AB  - The diagnosis of pulmonary arterial hypertension (PAH) is frequently delayed. We
      hypothesized that circulating angiogenic modulatory protein levels might
      correspond with vascular remodeling activity and serve as sensitive biomarkers of
      PAH. Levels of soluble endoglin (sEng), soluble vascular endothelial growth
      factor receptor-1 (sVEGFR1), N-terminal brain natriuretic peptide (NT-proBNP), C
      reactive protein (CRP), and other biomarkers were measured in peripheral blood
      from 97 PAH patients, 16 first-degree relatives of idiopathic or heritable
      pulmonary arterial hypertension (HPAH) patients, and 56 controls, and correlated
      with disease, functional class, hemodynamic parameters, exercise capacity, and
      transplant-free survival. Endoglin expression was analyzed in lung tissues of six
      individuals with idiopathic or HPAH and four individuals without PAH. Levels of
      sEng, sVEGFR1, CRP, and NT-proBNP were elevated in Group I PAH of diverse
      etiologies, with sEng performing better than NT-proBNP in detecting PAH (receiver
      operator characteristic-area-under-the curve [ROC-AUC] of 0.82 +/- 0.03 vs. 0.71
      +/- 0.05, P = 0.016). While sEng, sVEGFR1, and NT-proBNP correlated with New York
      Heart Association (NYHA) class, sEng levels were more sensitive than NT-proBNP in
      detecting NYHA Class I-II disease (ROC-AUC of 0.88 +/- 0.05 vs. 0.67 +/- 0.08, P
      = 0.028). sEng, sVEGFR1, CRP, and NT-proBNP predicted transplant-free survival by
      univariate Cox regression. After adjusting for NT-proBNP levels, each of the
      other three markers predicted transplant-free survival. In multivariate analysis,
      sEng and CRP were independent predictors of survival. Endoglin expression was
      markedly enhanced in the microvascular endothelium and endovascular lesions of
      PAH versus control lung tissues. Circulating angiogenic proteins sEng and sVEGFR1
      are sensitive markers of prognosis and function in Group I PAH, including mildly
      symptomatic disease, and may provide unique noninvasive data reflecting
      underlying remodeling activity. 

PMID- 24015339
TI  - A multicenter, retrospective study of patients with pulmonary arterial
      hypertension transitioned from parenteral prostacyclin therapy to inhaled
      iloprost.
AB  - Pulmonary arterial hypertension (PAH) is characterized by progressive increases
      in pulmonary vascular resistance, leading to right heart failure and death.
      Guidelines recommend customization of treatment, necessitating the development of
      effective strategies for transitioning patients among treatments. In this study,
      we characterized our experience with patient transitions from parenteral
      prostacyclin to inhaled iloprost. We retrospectively assessed records from 11
      centers of 37 consecutive patients with PAH aged >= 18 years who were treated
      with intravenous (IV) or subcutaneous (SC) prostacyclin analogues and
      transitioned to inhaled iloprost. The transition period began on the first day of
      inhaled iloprost with the intent of discontinuing parenteral prostacyclin and
      ended on the first day on inhaled iloprost free of parenteral prostacyclin.
      Persistence was defined as the absence of (1) parenteral prostacyclin while
      remaining on inhaled iloprost during post-transition Days 1-90 and (2) no
      reinitiation of parenteral prostacyclin during post-transition Days 90-365. All
      patients were clinically stable before transitioning to inhaled iloprost. The
      mean age was 46.5 years, 70.3% were female, 51.4% had idiopathic PAH, and 43.0%
      were in New York Heart Association Functional Class III. Among patients with an
      overlapping transition, the mean transition period was 10.5 days. A transition
      dosing algorithm was used in 10 patients (27.0%). At one year, 78.4% of the
      patients remained persistent on inhaled iloprost and 81.1% were free of clinical
      worsening. In selected patients on background oral PAH therapy, transitioning
      from parenteral prostacyclin to inhaled iloprost appears safe and feasible and is
      associated with long-term success. Further study is needed to define the optimal
      patient selection criteria and transition algorithm. 

PMID- 24015340
TI  - Provider recognition and response to echocardiographic findings indicating
      pulmonary hypertension in the Veterans affairs medical center population.
AB  - PH occurs alone or in association with many disorders. Many patients with
      transthoracic echocardiography (TTE) findings suggesting PH never receive
      additional evaluation. Patient characteristics and echocardiographic data
      associated with increased recognition of PH have not been fully evaluated. We
      evaluated TTE reports at the Cincinnati Veterans Affairs Medical Center from 2005
      to 2006 retrospectively for findings highly indicative of PH: Estimated systolic
      pulmonary artery pressure (sPAP) >=40 mmHg, increased right atrial or right
      ventricular (RV) size, or reduced RV function. Only patients with left
      ventricular ejection fraction (LVEF) >=50% and no known diagnosis of PH were
      included. Patient characteristics, TTE findings, provider recognition rates, and
      subsequent referral for additional evaluation were assessed. A total of 227 of
      3,960 (5.7%) TTE reports revealed findings indicating possible PH. Providers
      acknowledged possible PH in 53 (23.4%) reports. Recognized PH was predicted by
      increased RV size (odds ratio (OR) = 5.07, P < 0.001), increased right atrial
      dimension (OR = 6.45, P < 0.001), decreased RV function (OR = 8.86, P < 0.001),
      and increased PAP (OR = 1.04 corresponding to each unit increase of PAP, P <
      0.01). Patients with comorbid obstructive sleep apnea (OSA), interstitial lung
      disease, and dyspnea were also more likely to be recognized (OR = 3.63, P =
      0.021; OR = 10.98, P = 0.004; OR = 2.39, P = 0.007, respectively). The 12-month
      mortality rate for recognized patients, 11.3% (7/53), was lower than for
      unrecognized patients, 25.3% (44/174; P = 0.03). Providers recognized less than
      one in four patients with echocardiographic evidence suggesting PH.
      Echocardiography reports revealing higher PAP and right heart dilation and
      dysfunction are associated with increased acknowledgement of possible PH. 

PMID- 24015342
TI  - Comparison of drugs for pulmonary hypertension reversibility testing: A meta
      analysis.
AB  - Multiple drugs are used for reversibility testing of pulmonary hypertension (PH)
      in advanced heart failure (HF), especially in the process of heart transplant
      evaluation. Effects of these drugs were never systematically compared. The aim of
      this meta-analysis was to compare hemodynamic effects of different drugs. We
      identified 20 prospective studies reporting hemodynamic variables before and
      after acute pharmacologic testing for PH reversibility in patients with advanced
      HF. The data from individual studies were grouped by an outcome measure and
      analyzed. A mixed model meta-analysis was performed using SAS to give weighted
      mean effect of pre- and post-test change and inverse variance. The mean effects
      were weighted by the published sample size. Prostacyclin, inhaled or intravenous,
      and prostaglandin E1 (PGE1) had the most potent effect on pulmonary vascular
      resistance (PVR). Sodium nitroprusside and nitroglycerin decreased pulmonary
      capillary wedge pressure (PCWP), and mean pulmonary arterial pressure (MPAP)
      better than other drugs. Sildenafil provided overall good hemodynamic outcomes
      but was not the strongest drug with regard to any particular outcome. PCWP, MPAP,
      and systolic pulmonary arterial pressure respond better to nitroglycerin and
      sodium nitroprusside than to other drugs in the setting of reversibility testing.
      Prostacyclin and PGE1 are superior to other drugs in their acute effects on PVR. 

PMID- 24015341
TI  - Optimization of isolated perfused/ventilated mouse lung to study hypoxic
      pulmonary vasoconstriction.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is a compensatory physiological
      mechanism in the lung that optimizes the matching of ventilation to perfusion and
      thereby maximizes gas exchange. Historically, HPV has been primarily studied in
      isolated perfused/ventilated lungs; however, the results of these studies have
      varied greatly due to different experimental conditions and species. Therefore,
      in the present study, we utilized the mouse isolated perfused/ventilated lung
      model for investigation of the role of extracellular Ca(2+) and caveolin-1 and
      endothelial nitric oxide synthase expression on HPV. We also compared HPV using
      different perfusate solutions: Physiological salt solution (PSS) with albumin,
      Ficoll, rat blood, fetal bovine serum (FBS), or Dulbecco's Modified Eagle Medium
      (DMEM). After stabilization of the pulmonary arterial pressure (PAP), hypoxic (1%
      O2) and normoxic (21% O2) gases were applied via a ventilator in five-minute
      intervals to measure HPV. The addition of albumin or Ficoll with PSS did not
      induce persistent and strong HPV with or without a pretone agent. DMEM with the
      inclusion of FBS in the perfusate induced strong HPV in the first hypoxic
      challenge, but the HPV was neither persistent nor repetitive. PSS with rat blood
      only induced a small increase in HPV amplitude. Persistent and repetitive HPV
      occurred with PSS with 20% FBS as perfusate. HPV was significantly decreased by
      the removal of extracellular Ca(2+) along with addition of 1 mM EGTA to chelate
      residual Ca(2+) and voltage-dependent Ca(2+) channel blocker (nifedipine 1 MUM).
      PAP was also reactive to contractile stimulation by high K(+) depolarization and
      U46619 (a stable analogue of thromboxane A2). In summary, optimal conditions for
      measuring HPV were established in the isolated perfused/ventilated mouse lung.
      Using this method, we further confirmed that HPV is dependent on Ca(2+) influx. 

PMID- 24015343
TI  - Cardiopulmonary exercise test findings in symptomatic mustard gas exposed cases
      with normal HRCT.
AB  - Many patients with sulfur mustard (SM) exposure present dyspnea in exertion while
      they have a normal pulmonary function test (PFT) and imaging. The cardiopulmonary
      exercise test (CPET) has been used for evaluation of dyspnea in exertion among
      patients with different pulmonary disorders focusing on assessing gas exchange.
      We evaluated subjects who were exposed to SM with normal imaging compared to the
      controls with CPET. A case-control study was carried out on two groups in Tehran,
      Iran during 2010 to compare the CPET findings. The cases with a history of SM
      exposure and complaint of exertional dyspnea while they had normal physical
      examination, chest X-ray, PFT, and nonsignificant air trapping in lung high
      resolution computed tomography (HRCT) were included. A group of sex- and age
      matched healthy people were considered as controls. One hundred fifty-nine male
      patients (aged 37 +/- 4.3 years) were enrolled as a case group and ten healthy
      subjects (aged 35 +/- 5.9 years) as the control group. There was no significant
      difference in the demographic and baseline PFT characters between the two groups
      (P > 0.05). Only peak VO2/kg, VO2-predicted, and RR peak were statistically
      different between cases and controls (P < 0.05). Despite the fact that abnormal
      gas exchange may be present in our cases, it does not explain the low VO2 in
      CPET. Also, impaired cell O2 consumption could be a hypothesis for low VO2 in
      these cases. It seems that routine assessment of lung structure cannot be
      effectively used for discrimination of the etiology of dyspnea in low-dose SM
      exposed cases. 

PMID- 24015344
TI  - Preclinical pulmonary capillary endothelial dysfunction is present in brain dead
      subjects.
AB  - Pulmonary endothelium is a major metabolic organ affecting pulmonary and systemic
      vascular homeostasis. Brain death (BD)-induced physiologic and metabolic
      derangements in donors' lungs, in the absence of overt lung pathology, may cause
      pulmonary dysfunction and compromise post-transplant graft function. To explore
      the impact of BD on pulmonary endothelium, we estimated pulmonary capillary
      endothelium-bound (PCEB)-angiotensin converting enzyme (ACE) activity, a direct
      and quantifiable index of pulmonary endothelial function, in eight brain-dead
      patients and ten brain-injured mechanically ventilated controls. No subject
      suffered from acute lung injury or any other overt lung pathology. Applying
      indicator-dilution type techniques, we measured single-pass transpulmonary
      percent metabolism (%M) and hydrolysis (v) of the synthetic, biologically
      inactive, and highly specific for ACE substrate (3)H-benzoyl-Phe-Ala-Pro, under
      first order reaction conditions, and calculated lung functional capillary surface
      area (FCSA). Substrate %M (35 +/- 6.8%) and v (0.49 +/- 0.13) in BD patients were
      decreased as compared to controls (55.9 +/- 4.9, P = 0.033 and 0.9 +/- 0.15, P =
      0.033, respectively), denoting decreased pulmonary endothelial enzyme activity at
      the capillary level; FCSA, a reflection of endothelial enzyme activity per
      vascular bed, was also decreased (BD patients: 1,563 +/- 562 mL/min vs 4,235 +/-
      559 in controls; P = 0.003). We conclude that BD is associated with subtle
      pulmonary endothelial injury, expressed by decreased PCEB-ACE activity. The
      applied indicator-dilution type technique provides direct and quantifiable
      indices of pulmonary endothelial function at the bedside that may reveal the
      existence of preclinical lung pathology in potential lung donors. 

PMID- 24015345
TI  - Persistent pulmonary artery hypertension in patients undergoing balloon mitral
      valvotomy.
AB  - Pulmonary artery pressure (PAP) is known to regress after successful balloon
      mitral valvotomy (BMV). Data of persistent pulmonary artery hypertension (PPAH)
      following BMV is scarce. We analyzed the clinical, echocardiographic, and
      hemodynamic data of 701 consecutive patients who have undergone successful BMV in
      our institute from 1997 to 2003. Data of 287 patients who had PPAH (defined by
      pulmonary artery systolic pressure [PASP] of >= 40 mmHg at one year following
      BMV) were compared to the data of 414 patients who did not have PPAH. Patients
      who had PPAH were older (39.9 +/- 9.9 years vs. 29.4 +/- 10.1; P < 0.001). They
      had higher prevalence of atrial fibrillation (AF; 21.9 vs. 12.1%, P < 0.05),
      moderate or severe pulmonary artery hypertension (PAH) defined as PASP more than
      50 mmHg (43.5 vs. 33.8%, P = 0.00), anatomically advanced mitral valve disease as
      assessed by Wilkin's echocardiographic score > 8 (33.7 vs. 23.2%, P < 0.001), and
      coexistent aortic valve disease (45.6 vs. 37.9%, P < 0.001) at the baseline.
      Those patients with PPAH had comparatively lower immediate postprocedural mitral
      valve area (MVA). On follow-up of more than five years, the occurrence of
      restenosis (39.3 vs. 10.1%, P = 0.000), new onset heart failure (14% vs. 4%, P <
      0.05) and need for reinterventions (9.5% vs. 2.8%, P < 0.05) were higher in the
      PPAH group. Patients with PPAH were older, sicker, and had advanced rheumatic
      mitral valve disease. They had higher incidence of restenosis, new onset heart
      failure, and need for reinterventions on long term follow-up. PPAH represents an
      advanced stage of rheumatic valve disease and indicates chronicity of the
      disease, which may be the reason for the poorer prognosis of these patients.
      Patients with PPAH requires intense and more frequent follow-up. 

PMID- 24015346
TI  - Upper-body extracorporeal membrane oxygenation as a strategy in decompensated
      pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a disease with significant morbidity and
      mortality, particularly during an acute decompensation. We describe a single
      center experience of three patients with severe Group 1 PAH, refractory to
      targeted medical therapy, in which an extubated, nonsedated, extracorporeal
      membrane oxygenation (ECMO) strategy with an upper-body configuration was used as
      a bridge to recovery or lung transplantation. All three patients were extubated
      within 24 hours of ECMO initiation. Two patients were successfully bridged to
      lung transplantation, and the other patient was optimized on targeted PAH therapy
      with subsequent recovery from an acute decompensation. The upper-body ECMO
      configuration allowed for daily physical therapy, including one patient, who
      would otherwise have been unsuitable for transplantation, ambulating over 850
      meters daily. This series demonstrates the feasibility of using ECMO to bridge
      PAH patients to recovery or transplantation while avoiding the complications of
      immobility and invasive mechanical ventilation. 

PMID- 24015347
TI  - A case of recurrent pericardial constriction presenting with severe pulmonary
      hypertension.
AB  - Chronic constrictive pericarditis (CP) is a relatively rare condition in which
      the pericardium becomes fibrotic and noncompliant, eventually resulting in heart
      failure due to impaired ventricular filling. The only curative treatment is
      pericardiectomy. Classically, CP does not usually cause severe pulmonary
      hypertension. When attempting to differentiate CP from restrictive
      cardiomyopathy, the presence of severely elevated pulmonary arterial pressure is
      used as a diagnostic criterion ruling against CP. We present a case of proven
      recurrent pericardial constriction following pericardiectomy presenting with
      severe pulmonary hypertension. 

PMID- 24015348
TI  - Pulmonary arterial hypertension combined with a high cardiac output state: Three
      remarkable cases.
AB  - A congenital extrahepatic portosystemic venous shunt (CEPVS), also known as an
      Abernethy malformation, is a rare cause of pulmonary arterial hypertension (PAH).
      In this case series, we describe three male patients of 30, 23, and 27 years of
      age with PAH due to a CEPVS. In all three patients, a right heart catheterization
      revealed a high cardiac output. The aim of this case series is to make pulmonary
      hypertension physicians aware of the possibility of a CEPVS when PAH is
      accompanied with a high cardiac output state. 

PMID- 24015349
TI  - Regarding "A process-based review of mouse models of pulmonary hypertension".

PMID- 24015350
TI  - Author's Reply.

PMID- 24015351
TI  - Circulating endothelial progenitor cells in adults with sickle cell disease.

PMID- 24015352
TI  - Author's Reply.

PMID- 24015353
TI  - Effect of cerium oxide nanoparticles on intestinal serotonin in zebrafish.
AB  - Cerium oxide nanoparticles or nanoceria are emerging as a new and promising class
      of nanoparticle technology for biomedical applications. The safe implementation
      of these particles in clinical applications requires evaluation of their redox
      properties and reactivity that might cause neurotoxic effects by interacting with
      redox components of the physiological environment. We report in vitro and in vivo
      studies to evaluate the impact of nanoceria exposure on serotonin (5-HT), an
      important neurotransmitter that plays a critical role in various physiological
      processes including motility and secretion in the digestive system. In vitro
      studies of 5-HT in the presence of nanoceria using spectroscopic, electrochemical
      and surface characterization methods demonstrate that nanoceria interacts with 5
      HT and forms a surface adsorbed 5-HT-nanoceria complex. Further in vivo studies
      in live zebrafish embryos indicate depletion of the 5-HT level in the intestine
      for exposure periods longer than three days. Intestinal 5-HT was assessed
      quantitatively in live embryos using implantable carbon fiber microelectrodes and
      the results were compared to immunohistochemistry of the dissected intestine. 20
      and 50 ppm nanoparticle exposure decreased the 5-HT level to 20.5 (+/-1.3) and
      5.3 (+/-1.5) nM respectively as compared to 30.8 (+/-3.4) nM for unexposed
      control embryos. The results suggest that internalized nanoceria particles can
      concentrate 5-HT at the nanoparticle accumulation site depleting it from the
      surrounding tissue. This finding might have long term implications in the
      neurophysiology and functional development of organisms exposed to these
      particles through intended or unintended exposure.

PMID- 24015354
TI  - Mammalian genes induce partially reprogrammed pluripotent stem cells in non
      mammalian vertebrate and invertebrate species.
AB  - Cells are fundamental units of life, but little is known about evolution of cell
      states. Induced pluripotent stem cells (iPSCs) are once differentiated cells that
      have been re-programmed to an embryonic stem cell-like state, providing a
      powerful platform for biology and medicine. However, they have been limited to a
      few mammalian species. Here we found that a set of four mammalian transcription
      factor genes used to generate iPSCs in mouse and humans can induce a partially
      reprogrammed pluripotent stem cell (PRPSCs) state in vertebrate and invertebrate
      model organisms, in mammals, birds, fish, and fly, which span 550 million years
      from a common ancestor. These findings are one of the first to show cross-lineage
      stem cell-like induction, and to generate pluripotent-like cells for several of
      these species with in vivo chimeras. We suggest that the stem-cell state may be
      highly conserved across a wide phylogenetic range.
      DOI:http://dx.doi.org/10.7554/eLife.00036.001. 

PMID- 24015355
TI  - Ultrafast endocytosis at Caenorhabditis elegans neuromuscular junctions.
AB  - Synaptic vesicles can be released at extremely high rates, which places an
      extraordinary demand on the recycling machinery. Previous ultrastructural studies
      of vesicle recycling were conducted in dissected preparations using an intense
      stimulation to maximize the probability of release. Here, a single light stimulus
      was applied to motor neurons in intact Caenorhabditis elegans nematodes
      expressing channelrhodopsin, and the animals rapidly frozen. We found that docked
      vesicles fuse along a broad active zone in response to a single stimulus, and are
      replenished with a time constant of about 2 s. Endocytosis occurs within 50 ms
      adjacent to the dense projection and after 1 s adjacent to adherens junctions.
      These studies suggest that synaptic vesicle endocytosis may occur on a
      millisecond time scale following a single physiological stimulus in the intact
      nervous system and is unlikely to conform to current models of endocytosis.
      DOI:http://dx.doi.org/10.7554/eLife.00723.001. 

PMID- 24015356
TI  - DNA methylation presents distinct binding sites for human transcription factors.
AB  - DNA methylation, especially CpG methylation at promoter regions, has been
      generally considered as a potent epigenetic modification that prohibits
      transcription factor (TF) recruitment, resulting in transcription suppression.
      Here, we used a protein microarray-based approach to systematically survey the
      entire human TF family and found numerous purified TFs with methylated CpG (mCpG)
      dependent DNA-binding activities. Interestingly, some TFs exhibit specific
      binding activity to methylated and unmethylated DNA motifs of distinct sequences.
      To elucidate the underlying mechanism, we focused on Kruppel-like factor 4
      (KLF4), and decoupled its mCpG- and CpG-binding activities via site-directed
      mutagenesis. Furthermore, KLF4 binds specific methylated or unmethylated motifs
      in human embryonic stem cells in vivo. Our study suggests that mCpG-dependent TF
      binding activity is a widespread phenomenon and provides a new framework to
      understand the role and mechanism of TFs in epigenetic regulation of gene
      transcription. DOI:http://dx.doi.org/10.7554/eLife.00726.001. 

PMID- 24015357
TI  - High-order social interactions in groups of mice.
AB  - Social behavior in mammals is often studied in pairs under artificial conditions,
      yet groups may rely on more complicated social structures. Here, we use a novel
      system for tracking multiple animals in a rich environment to characterize the
      nature of group behavior and interactions, and show strongly correlated group
      behavior in mice. We have found that the minimal models that rely only on
      individual traits and pairwise correlations between animals are not enough to
      capture group behavior, but that models that include third-order interactions
      give a very accurate description of the group. These models allow us to infer
      social interaction maps for individual groups. Using this approach, we show that
      environmental complexity during adolescence affects the collective group behavior
      of adult mice, in particular altering the role of high-order structure. Our
      results provide new experimental and mathematical frameworks for studying group
      behavior and social interactions. DOI:http://dx.doi.org/10.7554/eLife.00759.001. 

PMID- 24015358
TI  - Mechanism of synergistic activation of Arp2/3 complex by cortactin and N-WASP.
AB  - Nucleation promoting factors (NPFs) initiate branched actin network assembly by
      activating Arp2/3 complex, a branched actin filament nucleator. Cellular actin
      networks contain multiple NPFs, but how they coordinately regulate Arp2/3 complex
      is unclear. Cortactin is an NPF that activates Arp2/3 complex weakly on its own,
      but with WASP/N-WASP, another class of NPFs, potently activates. We dissect the
      mechanism of synergy and propose a model in which cortactin displaces N-WASP from
      nascent branches as a prerequisite for nucleation. Single-molecule imaging
      revealed that unlike WASP/N-WASP, cortactin remains bound to junctions during
      nucleation, and specifically targets junctions with a ~160-fold increased on rate
      over filament sides. N-WASP must be dimerized for potent synergy, and targeted
      mutations indicate release of dimeric N-WASP from nascent branches limits
      nucleation. Mathematical modeling shows cortactin-mediated displacement but not N
      WASP recycling or filament recruitment models can explain synergy. Our results
      provide a molecular basis for coordinate Arp2/3 complex regulation.
      DOI:http://dx.doi.org/10.7554/eLife.00884.001. 

PMID- 24015359
TI  - Cytoplasmic dynein crosslinks and slides anti-parallel microtubules using its two
      motor domains.
AB  - Cytoplasmic dynein is the predominant minus-end-directed microtubule (MT) motor
      in most eukaryotic cells. In addition to transporting vesicular cargos, dynein
      helps to organize MTs within MT networks such as mitotic spindles. How dynein
      performs such non-canonical functions is unknown. Here we demonstrate that dynein
      crosslinks and slides anti-parallel MTs in vitro. Surprisingly, a minimal dimeric
      motor lacking a tail domain and associated subunits can cause MT sliding. Single
      molecule imaging reveals that motors pause and frequently reverse direction when
      encountering an anti-parallel MT overlap, suggesting that the two motor domains
      can bind both MTs simultaneously. In the mitotic spindle, inward microtubule
      sliding by dynein counteracts outward sliding generated by kinesin-5, and we show
      that a tailless, dimeric motor is sufficient to drive this activity in mammalian
      cells. Our results identify an unexpected mechanism for dynein-driven microtubule
      sliding, which differs from filament sliding mechanisms described for other motor
      proteins. DOI:http://dx.doi.org/10.7554/eLife.00943.001. 

PMID- 24015360
TI  - Three-color single molecule imaging shows WASP detachment from Arp2/3 complex
      triggers actin filament branch formation.
AB  - During cell locomotion and endocytosis, membrane-tethered WASP proteins stimulate
      actin filament nucleation by the Arp2/3 complex. This process generates highly
      branched arrays of filaments that grow toward the membrane to which they are
      tethered, a conflict that seemingly would restrict filament growth. Using three
      color single-molecule imaging in vitro we revealed how the dynamic associations
      of Arp2/3 complex with mother filament and WASP are temporally coordinated with
      initiation of daughter filament growth. We found that WASP proteins dissociated
      from filament-bound Arp2/3 complex prior to new filament growth. Further,
      mutations that accelerated release of WASP from filament-bound Arp2/3 complex
      proportionally accelerated branch formation. These data suggest that while WASP
      promotes formation of pre-nucleation complexes, filament growth cannot occur
      until it is triggered by WASP release. This provides a mechanism by which
      membrane-bound WASP proteins can stimulate network growth without restraining it.
      DOI:http://dx.doi.org/10.7554/eLife.01008.001. 

PMID- 24015361
TI  - The tortoise and the hare revisited.
AB  - Optogenetics and electron microscopy reveal an ultrafast mode of synaptic vesicle
      recycling, adding a new twist to a 40-year-old controversy. 

PMID- 24015362
TI  - Making the most of methylation.
AB  - A high-throughput screening approach based on a protein microarray reveals that
      many human transcription factors interact specifically with methylated promoter
      sequences. 

PMID- 24015363
TI  - Human infections with avian influenza A(H7N9) virus in China: preliminary
      assessments of the age and sex distribution.

PMID- 24015364
TI  - Avian influenza A(H7N9) and the closure of live bird markets.

PMID- 24015365
TI  - The threat of chikungunya in Oceania.

PMID- 24015366
TI  - The tuberculosis profile of the Philippines, 2003-2011: advancing DOTS and
      beyond.
AB  - The Philippines is one of the highest tuberculosis (TB) burden countries in the
      world with nationwide coverage of directly observed treatment, short-course
      (DOTS) achieved in 2003. This study reports on the National TB Control Programme
      (NTP) surveillance data for the period 2003 to 2011. During this period, the
      number of TB symptomatics examined increased by 82% with 94% completing the
      required three diagnostic sputum microscopy examinations. Of the 1,379,390 cases
      diagnosed and given TB treatment, 98.9% were pulmonary TB cases. Of these, 54.9%
      were new smear-positive cases, 39.3% new smear-negative cases and 4.7% were cases
      previously treated. From 2008 to 2011, 50,030 TB cases were reported by non-NTP
      providers. Annual treatment success rates were over 85% with an average of 90%;
      the annual cure rates had an eight-year average of 82.1%. These surveillance data
      represent NTP priorities - the large proportion of smear-positive cases reflected
      the country's priority to treat highly infectious cases to cut the chain of
      transmission. The performance trend suggests that the Philippines is likely to
      achieve Millennium Development Goals and Stop TB targets before 2015.

PMID- 24015367
TI  - Assessment of gender distribution in dengue surveillance data, the Lao People's
      Democratic Republic.
AB  - OBJECTIVE: Adolescent and young adult males account for a large proportion of
      dengue cases reported through national surveillance systems in the Western
      Pacific Region. To preliminarily assess the validity of these observed
      distributions, a field investigation was conducted in the Lao People's Democratic
      Republic's Savannakhet Province in November 2011. METHODS: Mixed quantitative and
      qualitative methods were used. Dengue surveillance data from Savannakhet
      Province, and aggregate hospital admission data from the Savannakhet Provincial
      Hospital for outpatients and inpatients were analysed by age and sex.
      Unstructured informal interviews were conducted with local health care workers,
      primary and secondary school officials and villagers. RESULTS: An excess of males
      was found among reported dengue cases in Savannakhet Province in the 15-49 year
      age group. Females in the same age group, however, were found to access health
      care more than their male counterparts. Qualitative assessments attributed this
      distribution to young females being more health-conscious and having greater
      health care-seeking behaviour. DISCUSSION: The excess of male dengue cases in the
      surveillance data appeared to be associated with a truly higher risk of dengue
      rather than greater health care access or health care-seeking behaviour by young
      men. This investigation indicated the importance of assessing the reported
      surveillance data within the context of health care utilization behaviour of the
      population under surveillance.

PMID- 24015368
TI  - Oseltamivir resistance among influenza viruses: surveillance in northern Viet
      Nam, 2009-2012.
AB  - INTRODUCTION: Antiviral resistance has been reported in seasonal influenza A
      viruses and avian influenza A(H5N1) viruses in Viet Nam, raising concerns about
      the efficacy of treatment. METHODS: We analysed specimens from two sources during
      the period 2009-2012: influenza-positive samples from influenza-like illness
      patients at sentinel clinics in northern Viet Nam and isolates from patients with
      confirmed A(H5N1) infections. Pyrosequencing was used to detect mutations: H275Y
      [for A(H1N1) and A(H5N1)], E119V [for A(H3N2)] and I117V [for A(H5N1)]. A
      neuraminidase inhibition assay was used to determine the Inhibitory Concentration
      50 (IC50) values for all influenza A and B isolates. RESULTS: There were 341
      influenza A positive samples identified; influenza A(H1N1)pdm09 was identified
      most frequently (n = 215). In 2009, oseltamivir resistance was observed in 100%
      (19 of 19) of seasonal A(H1N1) isolates and 1.4% (3/215) of A(H1N1)pdm09
      isolates. This H275Y mutation was not found in influenza subtypes A(H5N1) or
      A(H3N2) isolates. DISCUSSION: In Viet Nam, seasonal and A(H5N1) influenza
      vaccines are not currently available; thus, effective treatment is required. The
      presence of oseltamivir-resistant viruses is therefore a concern. Active
      surveillance for oseltamivir resistance among influenza viruses circulating in
      Viet Nam should be continued.

PMID- 24015369
TI  - An increase in neural tube defect notifications, South Australia, 2009-2010.
AB  - INTRODUCTION: In South Australia, reporting of live births, stillbirths of at
      least 20 weeks or 400 g birth weight, termination of pregnancies and congenital
      anomalies is mandated. We describe the investigation of an increase in
      notifications of neural tube defects (NTDs) in South Australia in 2009 and 2010
      using data from several surveillance systems. METHODS: NTD trend data from 1966
      to 2010 were reviewed. Comparisons of pregnancies affected by an NTD in 2009 and
      2010 were made with pregnancies affected by an NTD in the period 2003-2008 and
      with all pregnancies in 2009 and 2010. Statistical analysis was undertaken using
      Poisson regression, chi(2) or Fisher's exact tests. RESULTS: The prevalence of
      NTD-affected pregnancies was 1.95 per 1000 births (39 cases) in 2010 and 1.91 per
      1000 births in 2009 (38 cases), the highest annual rates since 1991. Case series
      comparisons indicated women with NTD-affected pregnancies in 2009 and 2010 were
      less likely to be Caucasian compared with women who had NTD-affected pregnancies
      in the period 2003-2008. Women born in the Middle East and African region (n = 7)
      were significantly more likely to have NTD-affected pregnancies in the years 2009
      and 2010 (relative risk: 3.03; 95% confidence interval: 1.39-6.62) compared with
      women born in the Oceania region. DISCUSSION: The increased notifications of NTDs
      can only be partially explained by the increase in numbers of women from the
      Middle East and African region, with no other contributory causes revealed. This
      analysis highlighted areas where prevention efforts should be strengthened and
      surveillance data improved.

PMID- 24015370
TI  - Three cases of neonatal tetanus in Papua New Guinea lead to development of
      national action plan for maternal and neonatal tetanus elimination.
AB  - Maternal or neonatal tetanus causes deaths primarily in Asia and Africa and is
      usually the result of poor hygiene during delivery. In 2011, three neonatal
      tetanus cases were investigated in Papua New Guinea, and all three cases were
      delivered at home by untrained assistants. The babies were normal at birth but
      subsequently developed spasms. A neonatal tetanus case must be viewed as a
      sentinel event indicating a failure of public health services including
      immunization, antenatal care and delivery care. The confirmation of these cases
      led to the drafting of the Papua New Guinea National Action Plan for Maternal and
      Neonatal Tetanus Elimination. This included three rounds of a tetanus toxoid
      supplementary immunization campaign targeting women of childbearing age (WBCA)
      and strengthening of other clean delivery practices. The first immunization round
      was conducted in April and May 2012, targeting 1.6 million WBCA and achieved
      coverage of 77%. The government of Papua New Guinea should ensure detailed
      investigation of all neonatal tetanus cases reported in the health information
      system and perform subprovincial analysis of tetanus toxoid coverage following
      completion of all three immunization rounds. Efforts also should be made to
      strengthen clean delivery practices to help eliminate maternal and neonatal
      tetanus in Papua New Guinea. 

PMID- 24015371
TI  - Avian influenza A(H7N9): information-sharing through government web sites in the
      Western Pacific Region.

PMID- 24015372
TI  - Epidemiologic update on the dengue situation in the Western Pacific Region, 2011.
AB  - Dengue is an emerging vectorborne infectious disease that is a major public
      health concern in the Asia and the Pacific. Official dengue surveillance data for
      2011 provided by ministries of health were summarized as part of routine
      activities of the World Health Organization Regional Office for the Western
      Pacific. Based on officially reported surveillance data, dengue continued to show
      sustained activity in the Western Pacific Region. In 2011, Member States reported
      a total of 244,855 cases of which 839 died for a case fatality rate of 0.34%.
      More than 1000 cases were reported each from Cambodia, the Federated States of
      Micronesia, the Lao People's Democratic Republic, Malaysia, the Philippines, the
      Marshall Islands, Singapore and Viet Nam. Cambodia, the Federated States of
      Micronesia and the Marshall Islands reported higher activity relative to 2010.
      There continues to be great variability among the dengue-endemic countries and
      areas in the Region in the number of cases and serotype distribution. The
      continued high notification rate and complex dengue epidemiology in the Region
      highlight the need for information-sharing on a routine and timely basis.

PMID- 24015373
TI  - Cu/Nitroxyl Catalyzed Aerobic Oxidation of Primary Amines into Nitriles at Room
      Temperature.
AB  - An efficient catalytic method has been developed for aerobic oxidation of primary
      amines to the corresponding nitriles. The reactions proceed at room temperature
      and employ a catalyst consisting of (4,4'- t Bu2bpy)CuI/ABNO (ABNO = 9
      azabicyclo[3.3.1]nonan-3-one N-oxyl). The reactions exhibit excellent functional
      group compatibility and substrate scope, and are effective with benzylic, allylic
      and aliphatic amines. Preliminary mechanistic studies suggest that aerobic
      oxidation of the Cu catalyst is the turnover-limiting step of the reaction.

PMID- 24015374
TI  - Photocatalytic Conversion of CO2 to CO using Rhenium Bipyridine Platforms
      Containing Ancillary Phenyl or BODIPY Moieties.
AB  - Harnessing of solar energy to drive the reduction of carbon dioxide to fuels
      requires the development of efficient catalysts that absorb sunlight. In this
      work, we detail the synthesis, electrochemistry and photophysical properties of a
      set of homologous fac-ReI(CO)3 complexes containing either an ancillary phenyl
      (8) or BODIPY (12) substituent. These studies demonstrate that both the
      electronic properties of the rhenium center and BODIPY chromophore are maintained
      for these complexes. Photolysis studies demonstrate that both assemblies 8 and 12
      are competent catalysts for the photochemical reduction of CO2 to CO in DMF using
      triethanolamine (TEOA) as a sacrificial reductant. Both compounds 8 and 12
      display TOFs for photocatalytic CO production upon irradiation with light
      (lambdaex >= 400 nm) of ~5 hr-1 with TON values of approximately 20. Although
      structural and photophysical measurements demonstrate that electronic coupling
      between the BODIPY and fac-ReI(CO)3 units is limited for complex 12, this work
      clearly shows that the photoactive BODIPY moiety is tolerated during catalysis
      and does not interfere with the observed photochemistry. When taken together,
      these results provide a clear roadmap for the development of advanced rhenium
      bipyridine complexes bearing ancillary BODIPY groups for the efficient
      photocatalytic reduction of CO2 using visible light.

PMID- 24015375
TI  - Pharmacogenomic Discovery Delineating the Genetic Basis of Drug Response.
AB  - Personalized medicine has the promise to tailor medical care based on the
      patient's genetic make-up and clinical variables such as gender, race and
      exposure to environmental stimuli. Recent progress in pharmacogenetic and
      pharmacogenomic studies has suggested that drug response to therapeutic
      treatments is likely a complex trait influenced by a variety of genetic and non
      genetic factors. Identifying molecular targets (e.g., genetic variants)
      delineating the genetic basis of drug response could help understand the complex
      nature of drug response. The last decade has witnessed significant advances in
      genome-wide profiling technologies for genetic/epigenetic variations and gene
      expression. As an unbiased, cell-based model for pharmacogenomic discovery, a
      tremendous resource of whole-genome molecular targets has been accumulated for
      the HapMap lymphoblastoid cell lines (LCLs) during the past decade. The current
      progress, particularly in cancer pharmacogenomics, using the LCL model was
      reviewed to illustrate the potential impact of systems biology approaches on
      pharmacogenomic discovery.

PMID- 24015376
TI  - Prostanoids but not oral therapies improve right ventricular function in
      pulmonary arterial hypertension.
AB  - OBJECTIVES: This study hypothesized that right ventricular stroke work index
      (RVSWI) and pulmonary capacitance (PC) would increase after treatment for
      pulmonary arterial hypertension (PAH) and that prostanoids would have a stronger
      effect than oral therapy. BACKGROUND: Right ventricular (RV) function is a major
      determinant of outcome in patients with PAH. Little is known about the response
      of RV function or its hemodynamic determinants to PAH-specific therapy. METHODS:
      We reviewed hemodynamic and health data on 58 patients from an institutional
      registry and analyzed changes in hemodynamic status between diagnostic and first
      repeat catheterization after initiation of therapy for PAH. RESULTS: The RVSWI
      and PC increased significantly after therapy (p = 0.007 and p = 0.02,
      respectively). Improvement in RV function was limited to patients treated with
      prostanoid-only therapy (p = 0.04); no improvement was found in patients treated
      with oral therapy (p = 0.25). Patients with the poorest baseline RV function
      (lowest tertile) had the greatest improvement post-therapy (p = 0.005 and p <
      0.001 vs. middle and highest tertiles). The major determinant of RVSWI was change
      in stroke volume (r(s) = 0.54, p < 0.001), indicating RVSWI is an accurate
      reflection of RV function. CONCLUSIONS: Right ventricular function improves after
      therapy with regimens including prostanoids but not oral-only regimens. Patients
      with the least compensated RV function at diagnosis might derive the most benefit
      from therapy. Larger studies are needed to determine whether changes in RVSWI
      after therapy are associated with outcomes.

PMID- 24015377
TI  - Left Ventricular Energy Model Predicts Adverse Events in Women With Suspected
      Myocardial Ischemia: Results From The NHLBI-Sponsored Women's Ischemia Syndrome
      Evaluation (WISE) Study.
AB  - OBJECTIVES: To assess the prognostic value of a left ventricular energy-model in
      women with suspected myocardial ischemia. BACKGROUND: The prognostic value of
      internal energy utilization (IEU) of the left ventricle in women with suspected
      myocardial ischemia is unknown. METHODS: Women (n=227, mean age 59+/-12 years,
      range 31-86), with symptoms of myocardial ischemia, underwent myocardial
      perfusion imaging (MPI) assessment for regional perfusion defects along with
      measurement of ventricular volumes separately by gated Single Photon Emission
      Computed Tomography (SPECT) (n= 207) and magnetic resonance imaging (MRI)
      (n=203). During follow-up (40+/-17 months), time to first major adverse
      cardiovascular event (MACE, death, myocardial infarction or hospitalization for
      congestive heart failure) was analyzed using MRI and gated SPECT variables.
      RESULTS: Adverse events occurred in 31 (14%). Multivariable Cox models were
      formed for each modality: IEU and wall thickness by MRI (Chi-squared 34, p<0.005)
      and IEU and systolic blood pressure by gated SEPCT (Chi-squared 34, p<0.005). The
      models remained predictive after adjustment for age, disease history and
      Framingham risk score. For each Cox model, patients were categorized as high-risk
      if the model hazard was positive and not high-risk otherwise. Kaplan-Meier
      analysis of time to MACE was performed for high-risk vs. not high-risk for MR
      (log rank 25.3, p<0.001) and gated SEPCT (log rank 18.2, p<001) models.
      CONCLUSIONS: Among women with suspected myocardial ischemia a high internal
      energy utilization has higher prognostic value than either a low EF or the
      presence of a myocardial perfusion defect assessed using two independent
      modalities of MR or gated SPECT.

PMID- 24015378
TI  - Orally dissolving strips: A new approach to oral drug delivery system.
AB  - Recently, fast dissolving films are gaining interest as an alternative of fast
      dissolving tablets. The films are designed to dissolve upon contact with a wet
      surface, such as the tongue, within a few seconds, meaning the consumer can take
      the product without need for additional liquid. This convenience provides both a
      marketing advantage and increased patient compliance. As the drug is directly
      absorbed into systemic circulation, degradation in gastrointestinal tract and
      first pass effect can be avoided. These points make this formulation most popular
      and acceptable among pediatric and geriatric patients and patients with fear of
      choking. Over-the-counter films for pain management and motion sickness are
      commercialized in the US markets. Many companies are utilizing transdermal drug
      delivery technology to develop thin film formats. In the present review, recent
      advancements regarding fast dissolving buccal film formulation and their
      evaluation parameters are compiled. 

PMID- 24015379
TI  - Effect assessment of "film coating and packaging" on the photo-stability of
      highly photo-labile antihypertensive products.
AB  - INTRODUCTION: Lacidipine (LCDP) is chemically a "1, 4-dihydropyridine derivative"
      Ca+(2) channel blocker used as an antihypertensive. Type and extent of packaging
      have a strong influence on the photo-stability of the 1,4-dihydropyridine
      derivatives. In standard, light protection of drug substance/drug product can be
      obtained either by use of an opaque additive in the formulation that
      competitively absorbs or reflects light reaching the sample and/or by blocking
      the access of light to the drug through external protection by packaging.
      MATERIALS AND METHODS: External protection by covering tablets with an opaque
      film coating involving a light-reflecting inorganic pigment such as titanium
      dioxide and/or by using an opaque impermeable packaging material was an
      appropriate suitable option for establishing photo-stability. Thus, the main
      objective of the present study was to optimize the % level of film coating in
      LCDP core tablets, and selection of a final packaging material and its respective
      extent, that is, primary, secondary and/or tertiary packaging, for LCDP tablets.
      RESULTS AND CONCLUSION: The main objective (% level of film coating) was
      optimized by directly exposing core tablets, 1% w/w, 2% w/w and 3% w/w film
      coated tablets, to a light source as per Option-2 of ICH Q1B and its comparative
      analysis at the end of light exposure testing. The other objective (extent of
      drug product packaging) was established successfully by assessing whether or not
      an acceptable change has occurred at the end of the light exposure testing of the
      LCDP film-coated tablets in a direct exposure study or a primary immediate pack
      and/or secondary marketing pack.

PMID- 24015380
TI  - Superporous hybrid hydrogels based on polyacrylamide and chitosan:
      Characterization and in vitro drug release.
AB  - OBJECTIVE: Current research was aimed at the development of the drug delivery
      systems based on the superporous hydrogels (SPH) with the desired swelling and
      the mechanical properties. MATERIALS AND METHODS: Superporous hydrogel composites
      (SPHCs) and superporous hybrid hydrogels (SPHHs) based on the chitosan and the
      polyacrylamide were synthesized using the gas blowing technique. The prepared
      hydrogels were evaluated for swelling studies, mechanical strength and scanning
      electron microscopy. The selected hydrogels were loaded with the drug (verapamil
      hydrochloride) by aqueous loading method. Drug integrity with in polymeric
      network was evaluated via fourier transform infrared spectroscopy (FTIR), X-ray
      diffraction (X-RD), differential scanning calorimetry (DSC), proton nuclear
      magnetic resonance ((1)HNMR) studies. In vitro drug release studies were carried
      out using the united state pharmacopoeial (USP) dissolution apparatus (type II).
      RESULTS AND DISCUSSION: The mechanical strength was observed to be higher in SPH
      hybrids in comparison to that in SPHCs while no significant difference was
      observed in swelling behavior. In situ crosslinking of chitosan with
      glutaraldehyde (GA) may be responsible for high mechanical strength. The
      equilibrium swelling time was slight higher in SPHH than in SPHCs. The integrity
      of pores was maintained in ethanol treated hydrogels as observed in scanning
      electron micrographs. Whereas, freeze dried SPH samples showed non-uniform pores.
      No drug polymer interaction was observed as indicated by DSC, FTIR, X-RD and NMR
      studies. However, the crosslinking of chitosan with GA was clearly indicated by
      these studies. The in vitro drug release studies from SPH hybrids indicated
      initial fast release (65%) with in first 2 h and then sustained release at the
      end of 24 h (95%). The addition of hydroxypropyl methyl cellulose with drug;
      however, leads to a significant decrease in drug release (56% at the end of 24
      h). CONCLUSION: Superporous hybrid hydrogels can be promising devices for the
      sustained delivery of drug candidates to the gastrointestinal region.

PMID- 24015381
TI  - Self micro-emulsifying drug delivery system of tacrolimus: Formulation, in vitro
      evaluation and stability studies.
AB  - BACKGROUND: Tacrolimus has poor solubility in water ranging from 4 to 12 MUg/mL.
      The oral bio availabilities of tacrolimus is poor and exhibits high intra and
      inter-subject variability (4-89%, average 25%) in the liver and the kidney
      transplant recipients and in patients with renal impairment. AIM: The present
      study deals with the development and characterization of self-micro-emulsifying
      drug delivery system to improve the oral bioavailability of poorly soluble drug
      tacrolimus. MATERIALS AND METHODS: Solubility of the tacrolimus was estimated in
      various oils, surfactants, and co-surfactants. Various in vitro tests such as
      percentage transmittance, emulsification time, cloud point, precipitation, and
      thermodynamic stabilities were used to find out optimized formulations. Optimized
      liquid self micro-emulsifying (SMEDDS) were characterized by particle size
      analysis and converted in solid by using the Florite RE as an adsorbent, which is
      further characterized by differential scanning calorimetry (DSC), scanning
      electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FTIR), and particle size analysis. RESULTS: The optimized liquid
      SMEDDS formulation contained 10% Lauroglycol FCC as an oil, 60% Cremophor RH, and
      30% PEG (polyethylene glycol) 400 as a surfactant and co-surfactant respectively.
      The optimized liquid and solid SMEDDS showed higher drug release than the
      marketed capsule and pure API (active pharmaceutical ingredient) powder. For
      optimized liquid SMEDDS and solid SMEDDS, the globule sizes were found 113 nm and
      209 nm respectively. The solid state characterization of solid-SMEDDS by SEM,
      DSC, FTIR, and XRD revealed the absence of crystalline tacrolimus in the solid
      SMEDDS. Shelf-lives for liquid SMEDDS and solid SMEDDS were found to be 1.84 and
      2.25 year respectively. CONCLUSIONS: The results indicate that liquid SMEDDS and
      solid SMEDDS of tacrolimus, owing to nano-sized, have potential to enhance the
      absorption of the drug.

PMID- 24015382
TI  - Investigation of the ex vivo and in vivo iontophoretic delivery of aceclofenac
      from topical gels in Albino rats.
AB  - INTRODUCTION: Iontophoresis was used to enhance the delivery of aceclofenac (ACF)
      from topical gels formulated with various polymers for the purpose of relieving
      pain and inflammation. MATERIALS AND METHODS: Gels were formulated from
      hydroxypropyl methyl cellulose (HPMC), carbopol 934P, and sodium carboxymethyl
      cellulose (NaCMC). The formulations were evaluated for cathodal iontophoretic
      delivery of ACF through excised rat abdominal skin at three levels of current
      density of 0.5, 0.6 and 0.7 mA/cm(2). The in vivo effectiveness of the drug
      delivered passively as well as under the influence of iontophoresis at pH 7.4 at
      a current density of 0.5 mA/cm(2) was also investigated using male Albino rats
      with carrageenan induced paw edema. RESULTS AND DISCUSSION: In the ex vivo
      studies, though it was clear that iontophoresis significantly increased drug
      permeation through the excised skin from all formulations; the percentage drug
      permeated from HPMC gels was superior to that from carbopol 934P or NaCMC gels
      but increased with an increase in the current density only for the former. The
      steady state flux, permeability coefficient, enhancement factor were
      significantly greater from HPMC gels than from the gels of the ionic polymers due
      to the interference of competitive ions. With iontophoresis, the carrageenan
      induced paw edema was significantly reduced by 61.53% (P < 0.01) for HPMC gels as
      compared to the control although passive permeation without iontophoresis showed
      a 54.6% reduction (P < 0.05) at the end of 4 h. CONCLUSION: The results of the
      study indicate that ACF could be administered topically by using iontophoresis
      from a suitably formulated gel for effective control of pain and inflammation.

PMID- 24015384
TI  - Reader's Forum.

PMID- 24015383
TI  - Oral buccoadhesive films of ondansetron: Development and evaluation.
AB  - INTRODUCTION: Difficulty or inability in swallowing tablets/capsules during or
      after chemotherapy is common due to chemotherapy induced nausea and vomiting in
      patients. Buccoadhesive films of ondansetron hydrochloride were prepared for the
      prevention and treatment of chemotherapy-induced emesis. Films of varying
      polymeric composition were prepared in order to facilitate initial as well as
      prolonged drug release that could take care of acute as well as delayed emesis.
      MATERIALS AND METHODS: Mucoadhesive films were prepared using polymers such as
      hydroxypropyl methylcellulose (HPMC) E5, HPMC K100, and Eudragit((r)) NE 30 D.
      The effect of concentration of these polymers on physical properties and drug
      release were studied. All the films were prepared by solvent casting method. In
      another part of the study, the effect of drug concentration on physical and
      mucoadhesive properties of film were assessed, keeping the polymer concentration
      fixed. RESULTS: Films containing HPMC showed good mucoadhesion. Increasing the
      concentration of Eudragit((r)) NE 30 D in the films retarded drug release and
      increased residence time, however, reduced mucoadhesion. At a fixed polymer
      concentration and ratio, films prepared using an increased drug content showed an
      increased mucoadhesion. CONCLUSION: Films prepared using HPMC E5 (1000 mg), HPMC
      K100 (500 mg), and Eudragit((r)) NE 30 D (750 mg) provided initial rapid followed
      by sustained drug release over a period of 6 h. Given the promising results, the
      study concluded that the developed buccal films have the potential to release
      ondansetron required for chemotherapy induced acute and delayed emesis.

PMID- 24015385
TI  - Three-dimensional evaluation of the relationship between nasopharyngeal airway
      shape and adenoid size in children.
AB  - OBJECTIVE: To evaluate the shapes and sizes of nasopharyngeal airways by using
      cone-beam computed tomography and to assess the relationship between
      nasopharyngeal airway shape and adenoid hypertrophy in children. METHODS: Linear
      and cross-sectional measurements on frontal and sagittal cross-sections
      containing the most enlarged adenoids and nasopharyngeal airway volumes were
      obtained from cone-beam computed tomography scans of 64 healthy children (11.0 +/
      1.8 years), and the interrelationships of these measurements were evaluated.
      RESULTS: On the basis of frontal section images, the subjects' nasopharyngeal
      airways were divided into the following 2 types: the broad and long type and the
      narrow and flat type. The nasopharyngeal airway sizes and volumes were smaller in
      subjects with narrow and flat airways than in those with broad and long airways
      (p < 0.01). Children who showed high adenoid-nasopharyngeal ratios on sagittal
      imaging, indicating moderate to severe adenoid hypertrophy, had the narrow and
      flat type nasopharyngeal airway (p < 0.01). CONCLUSIONS: Cone-beam computed
      tomography is a clinically simple, reliable, and noninvasive tool that can
      simultaneously visualize the entire structure and a cross section of the
      nasopharyngeal airway and help in measurement of adenoid size as well as airway
      volume in children with adenoid hypertrophy.

PMID- 24015386
TI  - Relationship between chin deviation and the position and morphology of the
      mandible in individuals with a unilateral cleft lip and palate.
AB  - OBJECTIVE: In this study, we aimed to examine the relationship between chin
      deviation and the positional and morphological features of the mandible and to
      determine the factors that contributed to chin deviation in individuals with a
      unilateral cleft lip and palate (UCLP). METHODS: Cone-beam computed tomography
      (CBCT) images of 28 adults with UCLP were analyzed in this study. Segmented three
      dimensional temporomandibular fossa and mandible images were reconstructed, and
      angular, linear, and volumetric parameters were measured. RESULTS: For all 28
      individuals, the chin was found to deviate to the cleft side by 1.59 mm.
      Moreover, among these 28 individuals, only 7 showed distinct (more than 4 mm)
      chin deviation, which was toward the cleft side. Compared to the non-cleft side,
      the mandibular body length, frontal ramal inclination, and vertical position of
      the condyle were lower and inclination of the temporomandibular fossa was steeper
      on the cleft side. Furthermore, the differences in inclination of the
      temporomandibular fossa, mandibular body length, ramus length, and condylar
      volume ratio (non-deviated/deviated) were positively correlated with chin
      deviation. CONCLUSIONS: UCLP individuals show mild chin deviation to the cleft
      side. Statistical differences were noted in the parameters that represented
      positional and morphological asymmetries of the mandible and temporomandibular
      fossa; however, these differences were too small to indicate clinical
      significance.

PMID- 24015387
TI  - Soft-tissue thickness of South Korean adults with normal facial profiles.
AB  - OBJECTIVE: To standardize the facial soft-tissue characteristics of South Korean
      adults according to gender by measuring the soft-tissue thickness of young men
      and women with normal facial profiles by using three-dimensional (3D)
      reconstructed models. METHODS: Computed tomographic images of 22 men aged 20 - 27
      years and 18 women aged 20 - 26 years with normal facial profiles were obtained.
      The hard and soft tissues were three-dimensionally reconstructed by using Mimics
      software. The soft-tissue thickness was measured from the underlying bony surface
      at bilateral (frontal eminence, supraorbital, suborbital, inferior malar, lateral
      orbit, zygomatic arch, supraglenoid, gonion, supraM2, occlusal line, and subM2)
      and midline (supraglabella, glabella, nasion, rhinion, mid-philtrum,
      supradentale, infradentale, supramentale, mental eminence, and menton) landmarks.
      RESULTS: The men showed significantly thicker soft tissue at the supraglabella,
      nasion, rhinion, mid-philtrum, supradentale, and supraglenoid points. In the
      women, the soft tissue was significantly thicker at the lateral orbit, inferior
      malar, and gonion points. CONCLUSIONS: The soft-tissue thickness in different
      facial areas varies according to gender. Orthodontists should use a different
      therapeutic approach for each gender.

PMID- 24015388
TI  - Fatigue resistance, debonding force, and failure type of fiber-reinforced
      composite, polyethylene ribbon-reinforced, and braided stainless steel wire
      lingual retainers in vitro.
AB  - OBJECTIVE: To analyze the fatigue resistance, debonding force, and failure type
      of fiber-reinforced composite, polyethylene ribbon-reinforced, and braided
      stainless steel wire lingual retainers in vitro. METHODS: Roots of human
      mandibular central incisors were covered with silicone, mimicking the periodontal
      ligament, and embedded in polymethylmethacrylate. The specimens (N = 50), with
      two teeth each, were randomly divided into five groups (n = 10/group) according
      to the retainer materials: (1) Interlig (E-glass), (2) everStick Ortho (E-glass),
      (3) DentaPreg Splint (S2-glass), (4) Ribbond (polyethylene), and (5) Quad Cat
      wire (stainless steel). After the recommended adhesive procedures, the retainers
      were bonded to the teeth by using flowable composite resin (Tetric Flow). The
      teeth were subjected to 10,00,000 cyclic loads (8 Hz, 3 - 100 N, 45 degrees 
      angle, under 37 +/- 3C water) at their incisoproximal contact, and debonding
      forces were measured with a universal testing machine (1 mm/min crosshead speed).
      Failure sites were examined under a stereomicroscope (*40 magnification). Data
      were analyzed by one-way analysis of variance. RESULTS: All the specimens
      survived the cyclic loading. Their mean debonding forces were not significantly
      different (p > 0.05). The DentaPreg Splint group (80%) showed the highest
      incidence of complete adhesive debonding, followed by the Interlig group (60%).
      The everStick Ortho group (80%) presented predominantly partial adhesive
      debonding. The Quad Cat wire group (50%) presented overlying composite
      detachment. CONCLUSIONS: Cyclic loading did not cause debonding. The retainers
      presented similar debonding forces but different failure types. Braided stainless
      steel wire retainers presented the most repairable failure type.

PMID- 24015390
TI  - Correction of palatally displaced maxillary lateral incisors without brackets.
AB  - This article describes the orthodontic treatment of a 25-year-old Korean female
      patient with anterior crowding, including palatally displaced lateral incisors.
      Her facial profile was satisfactory, but 3.5 mm of maxillary anterior crowding
      was observed. To correct this crowding, we decided to minimize the use of the
      conventional fixed orthodontic appliances and employed a less bulky and more
      aesthetic appliance for applying light continuous force. We determined the final
      positions of the maxillary teeth via a working model for diagnostic set up and
      achieved space gaining and alignment with simple Ni-Ti spring and stainless steel
      round tubes. Tooth alignment was achieved efficiently and aesthetically without
      the conventional brackets. 

PMID- 24015389
TI  - Psychosocial impact of malocclusion in Spanish adolescents.
AB  - OBJECTIVE: To evaluate the psychosocial impact of malocclusion, determine its
      relationship with the severity of malocclusion, and assess the influence of
      gender and social class on this relationship in adolescents. METHODS: A random
      sample of 627 Spanish adolescents aged 12 - 15 years underwent intraoral
      examinations by 3 calibrated examiners (intraexaminer and interexaminer kappa >
      0.85) at their schools. Psychosocial impact was measured through a self-rated
      Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ). The severity of
      malocclusion was measured by the Index of Orthodontic Treatment Need (IOTN).
      Gender and social class were also recorded. RESULTS: The total PIDAQ score and
      those of its 4 subscales, social impact, psychological impact, aesthetic concern,
      and dental self-confidence, presented significant differences (p <= 0.05 by
      analysis of variance) and linear relationships with the IOTN grades (p <= 0.05 by
      linear regression). Stepwise linear regression models showed that the IOTN dental
      health component was a predictive variable of the total and subscale PIDAQ
      scores. Neither gender nor social class was an independent predictive variable of
      this relationship, except the linear model for psychological impact, where gender
      was a predictive variable. The occlusal conditions responsible for higher PIDAQ
      scores were increased overjet, impeded eruption, tooth displacement, and
      increased overbite. CONCLUSIONS: Malocclusion has a psychological impact in
      adolescents and this impact increases with the severity of malocclusion. Social
      class may not influence this association, but the psychological impact seems to
      be greater among girls.

PMID- 24015391
TI  - My African experiences.

PMID- 24015392
TI  - A versatile chemical called chlorine.

PMID- 24015393
TI  - The Brown Kenya Medical Exchange Program: an overview.

PMID- 24015394
TI  - Brown Kenya Program: the growth of a progressive partnership.

PMID- 24015395
TI  - Practical aspects of the Kenya Medical Exchange Program.

PMID- 24015396
TI  - The Medical Exchange: Brown, Moi students/residents share their experiences.

PMID- 24015397
TI  - Reexpansion pulmonary edema following thoracentesis.

PMID- 24015398
TI  - The future of generic HIV drugs in Rhode Island.
AB  - The number of HIV-infected persons in the United States continues to increase and
      most patients with HIV will be on antiretroviral therapy (ART) for many decades.
      The introduction of generic antiretroviral medications has the potential for
      significant cost savings which may then be accompanied by improved access. State
      AIDS Drug Assistance Programs will be made more effective by the switch to
      generic ARTs. Cost savings and barriers to the introduction of generic ART are
      discussed. 

PMID- 24015399
TI  - RI influenza surveillance summary 2012-2013.

PMID- 24015400
TI  - A novel, post-column micro-membrane reactor for fluorescent analysis of protein
      in capillary electrophoresis.
AB  - Based on the semipermeability of hollow fiber membranes, a post-column membrane
      reactor was developed for capillary electrophoresis (CE)-laser induced
      fluorescence (LIF) analysis of proteins by using a hollow fiber membrane to
      connect the separation and detection capillaries. The membrane length between the
      separation and detection capillaries was 1 mm. Driven by the chemical potential
      difference between the separation buffer inside the membrane and the fluorescence
      derivatization solution outside the membrane, the derivatization reagent can be
      easily drawn into hollow fiber membrane to react with proteins. Also, the
      separation buffer can be adjusted by the derivatization solution to match the
      conditions of derivatization without sample loss. The effect of the separation
      buffer on the derivatization reaction was investigated and the results showed
      that even a strong acidic solution and multiple additives can be adopted in the
      separation buffer without destroying the post-column derivatization of proteins.
      Under the optimized conditions, the highly sensitive detection of BSA was
      achieved with a detection limit of 3.3 nmol L(-1) and a linear calibration range
      from 0.007 to 0.1 mg mL(-1). The proposed CE-LIF system with a post-column
      membrane reactor was also successfully applied to the separation and detection of
      proteins in rat liver and loach muscle. 

PMID- 24015401
TI  - Is the prevalence of visual impairment rising or falling in the people with
      diabetes mellitus? It depends on who you study.

PMID- 24015402
TI  - Sclerochoroidal calcification is primarily a scleral condition based on enhanced
      depth imaging optical coherence tomography.

PMID- 24015403
TI  - Isotope effect and multiscale physics in fusion plasmas.
AB  - The mechanism governing the impact of the mass isotope on plasma confinement is
      still one of the main scientific conundrums facing the magnetic fusion community
      after more than thirty years of intense research. We have investigated the
      properties of local turbulence and long-range correlations in hydrogen and
      deuterium plasmas in the TEXTOR tokamak. Experimental findings have shown a
      systematic increasing in the amplitude of long-range correlations during the
      transition from hydrogen to deuterium dominated plasmas. These results provide
      the first direct experimental evidence of the importance of multiscale physics
      for unraveling the physics of the isotope effect in fusion plasmas.

PMID- 24015404
TI  - Prof. Shahbudin H. Rahimtoola MB, FRCP, MACC, MACP, FESC, DSc (Hon) has been
      described as a cardiologist of the world and the father of research and clinical
      practice in myocardial hibernation.

PMID- 24015405
TI  - The strengths and limitations of the Japanese healthcare system.

PMID- 24015406
TI  - ACE inhibitor reduces radiation injury to myocardium.

PMID- 24015408
TI  - Guest editorial--ISCAS 2011 special issue.

PMID- 24015407
TI  - Emotional reactivity to emotional and smoking cues during smoking abstinence:
      potentiated startle and P300 suppression.
AB  - Negative affect is thought to be an important factor in the maintenance of
      cigarette smoking, and thus it is important to further develop objective measures
      of smoking-related emotional responses. Nonsmokers, non abstinent smokers, and
      abstinent smokers participated in a cue reactivity task where eyeblink startle
      amplitude and startle probe P300 (P3) suppression were measured during the
      presentation of emotional pictures.During unpleasant pictures, the amplitude of
      both measures was smaller in non abstinent smokers than in nonsmokers or
      abstinent smokers. P3 suppression, but not startle amplitude, was larger in
      abstinent smokers than in nonsmokers. Abstinence-induced increases in cigarette
      craving were associated with P3 suppression during tobacco-related pictures.
      Results suggest that tobacco abstinence increases emotional reactivity to
      unpleasant stimuli, which is consistent with negative reinforcement models of
      tobacco addiction.

PMID- 24015409
TI  - Guest editorial--special issue on selected papers from BioCAS 2011.

PMID- 24015411
TI  - Provider deals jump. Tenet's Vanguard play leads the pack.

PMID- 24015410
TI  - Sour earnings report. Federal inquiry, bad debt shake community health.

PMID- 24015412
TI  - Rethinking philanthropy. Hospitals, systems use income from donations for broader
      range of purposes.

PMID- 24015413
TI  - New collaborations. Providers partner to gain population health expertise.

PMID- 24015414
TI  - Dural involvement in skull base tumors--accuracy of preoperative radiological
      evaluation and intraoperative assessment.
AB  - BACKGROUND: Dural involvement is an important consideration in assessment of
      cranial base tumors dictating resectability and prognosis. Preoperative as well
      as intraoperative clues are valuable but not always correct. We evaluated a
      consecutive series of craniofacial resections at our center to correlate
      radiologically suspected dural involvement vis-a-vis intraoperative assessment
      and eventual pathology. METHODS: We conducted a retrospective analysis of cases
      of skull base tumors where potential dural involvement was considered. We
      recorded the preoperative radiological impression (contrast-enhanced magnetic
      resonance imaging) regarding dural involvement (normal, extradural, intradural,
      parenchymal disease), intraoperative impression (normal, adherent, subdural,
      parenchymal disease), and final histology (normal, reactive, tumor). We also
      recorded instances where the dura was resected and/or inadvertently breached and
      the incidence of postoperative cerebrospinal fluid leak and meningitis. RESULTS:
      One hundred twenty-seven cases were evaluated. Transcranial approaches were
      performed in 68 cases. Nineteen percent (24 cases) were endoscopic procedures.
      Dural resection was performed in 38 cases (30 being proven pathologically). The
      incidence of cerebrospinal fluid leak was 4.7%. The sensitivity, specificity,
      positive predictive value, and negative predictive value of magnetic resonance
      assessment were 34.5%, 97.9%, 83.3%, and 83.2%, respectively, providing an
      overall accuracy of 84%, and those for intraoperative dural adherence were 84.6%,
      85.6%, 44%, 97.6%, and 85.5.%, respectively. CONCLUSIONS: Preoperative magnetic
      resonance imaging, although a good modality for imaging the disease extent, may
      not always identify the extent of dural involvement. Intraoperative assessment
      therefore becomes very important especially when it is unequivocally normal. Both
      should be used to ensure accurate treatment strategies and tailor the need for
      dural resection.

PMID- 24015415
TI  - The effects of sevoflurane and isoflurane in nasal septal surgery.
AB  - OBJECTIVES: The objective of this study was to evaluate the effect of sevoflurane
      and isoflurane in nasal septal surgery in terms of intraoperative blood loss,
      operation time, recovery time, and especially postoperative pain. METHODS: A
      total of 90 elective nasal septal surgery patients between the ages of 19 and 58
      years (mean age, 32.95 years) who were classified as American Society of
      Anesthesiologists physical status I and II between January 2011 and June 2012
      were included the study. Patients were assigned by randomization to receive 1 of
      2 anesthetic agents (n = 45 patients each group): balanced general anesthesia
      with sevoflurane or isoflurane group. In all patients, the amount of
      intraoperative blood loss, the duration of operation, recovery time, and
      postoperative pain scores were recorded. RESULTS: The amount of perioperative
      bleeding in sevoflurane cases was less than that in the isoflurane group, and the
      difference was statistically significant (P G 0.05). Similarly, mean operative
      time was shorter in the sevoflurane group, and again the difference between 2
      groups was statistically significant (P G 0.05). No statistically significant
      differences were observed between the 2 groups with respect to the anesthesia
      duration, extubation time, recovery time, and postoperative pain scores (P 9
      0.05). CONCLUSIONS: Sevoflurane, which is one of the volatile anesthetics, leads
      to a lower amount of intraoperative bleeding, postoperative pain, and operation
      time than isoflurane during nasal septal surgery.

PMID- 24015416
TI  - Monobloc minus Le Fort II for single-stage treatment of the Apert phenotype.
AB  - Treatment of the Apert syndrome phenotype aims to correct airway obstruction,
      exorbitism, elevated intracranial pressure, midface hypoplasia, and malocclusion.
      Cranial vault expansion prevents elevated intracranial pressure, normalizes head
      shape, and protects the globes, but variation exists in surgical timing and
      osteotomy to treat the midface. We present the case of an 11-year-old female
      patient with Apert syndrome and no prior surgical interventions who presented
      with severe turribrachycephaly, exorbitism, severe midface retrusion, and
      apertognathia. A monobloc distraction with simultaneous Le Fort II distraction
      was planned using computer-aided design and modeling (CAD/CAM) techniques to
      provide for concurrent distraction of the segments in independent vectors without
      bony interferences. Monobloc minus Le Fort II distraction was performed without
      intraoperative complications. Surgical time was 340 minutes with an estimated
      blood loss of 1100 mL. Distraction began on postoperative day 5 at a rate of 1.5
      mm/day for the Le Fort II via an external Halo distractor and 1 mm/day for the
      monobloc segment via internal distractors anchored bitemporally. The monobloc was
      distracted a total of 17 mm in a horizontal vector, while the Le Fort II segment
      was distracted 18 mm horizontally and 5 mm inferiorly. The Halo distractor was
      removed 3 months following the procedure and the internal distractors 1 month
      later. Monobloc minus Le Fort II distraction enables correction of the Apert
      phenotype with a single-stage approach, potentially decreasing the burden of care
      with improved results. Utilization of CAD/CAM modeling allows for accurate
      planning of multisegment distraction in independent vectors without concerns for
      bony interferences.

PMID- 24015417
TI  - [Picture in clinical hematology].

PMID- 24015418
TI  - [Reconstruction for spinal cord injury].

PMID- 24015419
TI  - [Mechanism of electrical potential dynamics of lymph fluid in inner ear].

PMID- 24015420
TI  - [Diagnostic and treatment of allergic rhinitis].

PMID- 24015421
TI  - [Not Available].

PMID- 24015422
TI  - We are pleased to inform our readers that The Sixth Adam Smith Award in Mental
      Health Policy and Economics Research was presented. Introduction.

PMID- 24015423
TI  - Author's reply: To PMID 23229216.

PMID- 24015424
TI  - Electrocardiogram consistent with anterolateral myocardial injury in the setting
      of a spontaneous right-sided pneumothorax.

PMID- 24015425
TI  - Rare manifestations of coccidioidomycosis.
AB  - Involvement of the central nervous system and extrapulmonary sites by
      Coccidioides immitis is reported primarily in patients with cell-mediated immune
      deficiency. We present a case of a patient with no prior history of
      immunosuppression who presented to a public hospital in New Orleans with
      disseminated Coccidioides infection.

PMID- 24015426
TI  - A skin nodule in a 66-year-old man as sign of an ominous prognosis.
AB  - Skin metastases are common in lung cancer but are rarely noted as the presenting
      complaint. As evidence of dissemination, they, of course, carry an ominous
      prognosis. We present a case of metastatic adenocarcinoma of the lung in an
      otherwise healthy man, whose only symptom was a painless skin nodule.

PMID- 24015427
TI  - Splenic nodules at autopsy.
AB  - Gamna-Gandy bodies (GGBs), also known as hemosiderotic nodules, were first
      described in 1921 in association with sickle cell disease. Since then, they have
      been documented to occur in association with other pathological processes such as
      hemolytic anemia, congestive splenomegaly, hereditary hemochromatosis; and
      acquired hemosiderosis. Despite a uniquely characteristic microscopic appearance
      that is easily recognized by routine histopathologic examination, the precise
      significance of GGBs remains unknown. As such, documentation of GGBs in patients
      either by pathology or radiology should herald the presence of a systemic
      disorder such as sickle cell anemia or hemochromatosis wherein portal
      hypertension and/or congestive splenomegaly are present. In this article, we
      briefly present two autopsy cases from two patients with distinctly different
      clinical presentations wherein classic Gamna-Gandy bodies are illustrated on
      routine histopathologic examination.

PMID- 24015428
TI  - How natural disasters change natural patterns: coccidioidomycosis imported to New
      Orleans.
AB  - OBJECTIVE: To identify cases of coccidioidomycosis in the New Orleans area
      following Hurricane Katrina. METHODS: We performed clinical surveillance across
      multiple medical disciplines and among three major teaching hospitals in the
      greater NOLA area in the posthurricane period. Each case involved a detailed
      history, physical examination, laboratory evaluations, and, in the two fatal
      cases, a comprehensive postmortem examination. RESULTS: We identified four cases
      of coccidioidomycosis during the posthurricane period: three with disseminated
      disease and one with disease limited to the respiratory tract. Two patients were
      co-infected with HIV and died during hospitalization; one was only diagnosed at
      autopsy. The two immunocompetent patients responded well to antimicrobial
      therapy. CONCLUSIONS: A heightened awareness of non-endemic disease is warranted
      in the practice of postdisaster clinical medicine and public health, as
      demonstrated by the appearance of coccidioidomycosis in the traditionally
      nonendemic NOLA area following Hurricane Katrina.

PMID- 24015429
TI  - Left ventricular noncompaction cardiomyopathy.
AB  - Isolated Left Ventricular Non Compaction Cardiomyopathy (LVNCC) is a rare genetic
      cardiomyopathy characterized by a thickened left ventricle with two distinct
      layers - an inner noncompacted (spongy) layer and an outer compact (dense) layer.
      The spongy layer is composed of deep intertrabecular recesses. Familial and
      sporadic forms are known to exist and there is significant genetic heterogeneity
      among the inherited forms. Symptoms vary and range from asymptomatic to severe
      heart failure and sudden death. The clinical diagnosis of LVNCC can be
      challenging partly because there is currently no consensus for diagnostic
      criteria. As such, many affected individuals are, inopportunely, first diagnosed
      at post-mortem examination.

PMID- 24015430
TI  - Epidermoid cyst arising from an intrapancreatic accessory spleen: a case report
      and a review of the literature.
AB  - Accessory spleen is estimated to occur in 1 in 10 people in the general
      population, usually in the tail of the pancreas. Epidermoid cysts arising from
      ectopic spleen tissue in the tail of the pancreas are a benign and extremely rare
      pathology. Only 27 cases with such pathology have been reported in the English
      literature. Differentiating this pathology from other pancreatic pathologies,
      especially in the presence of a history of recent cancer, is almost impossible.
      In this article, we report a 36-year-old African-American woman with a history of
      colon cancer and hemicolectomy who was incidentally found to have a cystic lesion
      in the tail of her pancreas during surveillance abdominal imaging. After a distal
      pancreatectomy, the lesion was diagnosed to be an epidermoid cyst in an
      intrapancreatic accessory spleen. This is the first report of such pathology in a
      patient with a recent history of cancer. We propose that this pathology be
      considered as a differential diagnosis when assessing patients with cystic
      lesions in their pancreas, even when they have a history of previous
      malignancies.

PMID- 24015431
TI  - Treatment of chronic sickle cell leg ulcers with supplemental oxygen.

PMID- 24015432
TI  - Chest pains--a formal risk assessment of acute coronary syndrome.
AB  - Two patients presented on the same day with similar stories of chest pain,
      physical exams, laboratory results, and ECG findings. Applying formal risk
      assessment provided validation of the initial impression that one patient had a
      higher likelihood of acute coronary syndrome than the other patient. Using pre
      test probabilities of coronary artery disease, likelihood ratios of symptoms, and
      diagnostic tests, we demonstrate how to calculate a post-test probability for
      acute coronary syndrome (ACS). We discuss the importance of knowing disease
      prevalence and recognizing powerful tests. We also explore the variables for
      early risk stratification of ACS listed in the American College of
      Cardiology/American Heart Association guidelines. This demonstrates how the
      application of formal risk assessment can be used to teach clinical reasoning and
      improve clinical practice.

PMID- 24015433
TI  - Delayed traumatic lung herniation.
AB  - There are very few lung herniation cases described in literature. We present a
      case of a delayed lung herniation. In our case, the initial imaging was negative
      but patient developed a herniated lung during his hospital stay.

PMID- 24015434
TI  - ECG of the month. Electrocardiogram in an attempted suicide. Sinus bradycardia
      with an atrial escape complex, followed by a junctional escape rhythm with
      isorhythmic atrioventricular dissociation; voltage criteria for left ventricular
      hypertrophy.

PMID- 24015435
TI  - Radiology case of the month. An infant with leukocoria: persistent fetal
      vasculature syndrome. Persistent fetal vasculature syndrome (PFVS) of the right
      eye associated with microphthalmia, bilateral optic nerve and optic chiasm
      hypoplasia, and absence of the neurohypophysis.

PMID- 24015436
TI  - A case of disseminated cryptococcosis with skin manifestations in a patient with
      newly diagnosed HIV.
AB  - In this case report, we provide a concise review of the pathogenesis, clinical
      presentation, key diagnostic findings, and treatment options for Cryptococcus.
      Cryptococcus neoformans is a ubiquitous dimorphic fungus that can potentially be
      life threatening, especially in immunocompromised hosts. It commonly infects the
      respiratory tract or central nervous system. However, skin manifestations can be
      a marker of severe and disseminated disease, particularly in individuals at
      higher risk, including those patients with AIDS, cancer, long-term corticosteroid
      use, and organ transplant recipients. A timely diagnostic workup, including skin
      biopsy,blood cultures, and lumber puncture, is crucial since skin lesions may
      mimic other infectious processes. In addition, prompt, appropriate antifungal
      treatment should be initiatedto decrease morbidity and mortality.

PMID- 24015437
TI  - Acute onset of extreme shortness of breath.

PMID- 24015438
TI  - Ohio nurses are vital key to healthcare system transformation.

PMID- 24015439
TI  - Patient-centered medical homes--what is it?

PMID- 24015440
TI  - Live long and prosper.

PMID- 24015441
TI  - Data trans-par-en-cy in 1-2-3.

PMID- 24015442
TI  - What's going on with Medicaid?

PMID- 24015443
TI  - Two new laws with immediate impact.

PMID- 24015444
TI  - 89th General Assembly--Scott Smith's legislative review. AMS work on physicians'
      behalf in a Medicaid-centered session.

PMID- 24015445
TI  - Updates in palliative medicine.

PMID- 24015446
TI  - Payment reform at one year: much accomplished, much left to do.

PMID- 24015447
TI  - Aspergillus brain abscess.
AB  - Aspergillus brain abscess is a rare clinical entity, which remains a challenge to
      diagnose and treat. Most fungi are low virulence organisms, often living as
      commensals. They however, pose a considerable challenge in an immune-compromised
      host. Systemic steroids are commonly used in treatment of various inflammatory
      conditions. Despite their relatively safe profile, one peril of such treatment is
      immune suppression. It is prudent that physicians remain aware of the risk of
      various opportunistic infections in such patients. We present a case of fatal
      intra-cranial aspergillosis in an immuno-compromised patient on systemic
      steroids.

PMID- 24015448
TI  - Predictors of stage and the application of curative-intent surgery in pancreatic
      cancer: a population-based analysis from the Arkansas Cancer Registry.
AB  - BACKGROUND: The purpose of this study was to describe the characteristics of
      pancreatic cancer subjects within the state of Arkansas. METHODS: Pancreatic
      cancer patients diagnosed from 5/1997 to 12/2007 were identified from the
      Arkansas Cancer Registry. Analysis was performed to identify variables associated
      with advanced-stage and curative-intent surgery. RESULTS: For 3,227 subjects,
      only grade was associated with advanced stage pancreatic cancer. Age > 80,
      pancreatic cancer site not specified, and grade were associated with curative
      intent surgery. CONCLUSIONS: Studies utilizing the Arkansas Cancer Registry are
      feasible and can identify variables associated with stage and treatment.

PMID- 24015449
TI  - Oral and maxillofacial pathology case of the month. Foreign body giant cell
      reaction to cosmetic filler material Radiesse.

PMID- 24015450
TI  - A technique for fabricating a milled titanium complete-arch framework using a new
      CAD/CAM software and scanner with laser probe.
AB  - By using traditional casting procedures, accurately fitting of complete-arch
      frameworks that are screwed on multiple implants is difficult to achieve. The
      introduction of computer-aided design and manufacturing (CAD/CAM) techniques for
      fabricating custom 1-piece titanium frameworks simplifies this challenge and
      reduces time spent by the restorative dentist. This report presents a milled
      titanium complete-arch mandibular framework using a new planning software and a
      new scanner using non-contact laser probe, which eliminates the need for wax
      pattern fabrication.

PMID- 24015451
TI  - Predictable immediate loading of mandibular implants.
AB  - Technological advancements have resulted in modern dental implant protocols that
      provide the possibility to immediately load implants in fresh extraction sockets.
      This article briefly addresses various aspects to be considered such as computed
      tomography (CT), surgical guides, implant considerations for the edentulous
      patient, and considerations for immediate implant placement and loading. In this
      clinical case, immediate post-extraction implant placement with immediate loading
      was performed accurately because of the planning done with the CT scan. The use
      of a stereolithographic model and a surgical guide prevented technical
      difficulties and improved the predictability during the prosthetically driven
      surgery.

PMID- 24015452
TI  - Restoration of congenitally missing maxillary lateral incisors using mini
      implants.
AB  - In this author's opinion, the advent of mini implants, or small diameter implants
      (SDIs) as they are more frequently being called, are becoming in many situations
      a viable alternative to the more traditional root form implants. They offer
      advantages of less cost, a more simplified placement technique, usually faster
      healing times, and generally less post-operative complications. A case
      presentation is given to demonstrate their usage for a narrow ridge application
      to restore congenitally missing maxillary lateral incisors.

PMID- 24015453
TI  - Light-cured resin-based sealants have a significantly higher long-term retention
      rate than fluoride-containing light-cured resin-based sealants (UT CAT #2442).

PMID- 24015454
TI  - Wilcox-Jewitt obtunder syringe.

PMID- 24015455
TI  - Value for your profession: Why having a mobile-friendly website is so important.

PMID- 24015456
TI  - The participation in health-related research projects: compensated, reimbursed or
      gratuitous.

PMID- 24015457
TI  - [Accuracy of nursing interventions for patients with type 2 diabetes mellitus in
      outpatient consultation].
AB  - The objective of this study was to identify the accuracy of nursing interventions
      from the nursing diagnoses (ND) of patients who consulted in the Program for
      Diabetes Education, in outpatient care of the university hospital relating them
      with sociodemographic characteristics and comorbidities. It was a cross-sectional
      study of 136 patients with type 2 diabetes mellitus (DM2), with 77 (57%) women,
      with an average age of 66 +/- 9.38 years, and the presence of comorbidities in 97
      (71%), and using medications. A significant association was found between the NDs
      and the most frequently prescribed interventions. "nutritional counseling" (n=99;
      73%), "promotion of exercise" (n=64; 47%) and "teaching: feet care (n=48; 35%);
      however, not with the sociodemographic characteristics or comorbidities. The
      interventions most prescribed in nursing consultations showed ND accuracy for the
      domains of Promotion of Health and Nutrition, which are related to the principles
      of treatment for DM2: healthy eating, physical exercise and health education.

PMID- 24015458
TI  - [Association of Braden subscales with the risk of development of pressure ulcer].
AB  - Pressure ulcers (PU) may increase the incidence of hospital complications, and
      one should prevent this damage. The Braden Scale stands out as a tool to assess
      the risk of PU. The study aimed to identify changes in the score of the Braden
      subscales are associated with the risk of developing PCU. Logistic regression was
      used in a retrospective cohort study conducted in Hospital de Clinicas de Porto
      Alegre in adults hospitalized in surgical clinical units from October 2005 to
      June 2006. We evaluated the records database of 1503 patients with a mean aged
      55.5 +/- 16 years, 52.7% female. The incidence of PU was 1.8% and was associated
      with diabetes and heart failure. There was a higher PU in patients worst in
      sensory perception, mobility, and activity and the presence of moisture. No
      association was found between nutrition and PU. Except nutrition, the other
      Braden sub-scales shown to be predictive of PU.

PMID- 24015459
TI  - [Construction of an educational technology for teaching about nursing on
      peripheral venipuncture].
AB  - The aim of the study was to describe the construction of a course on peripheral
      venipuncture using the Information and Communication Technologies. This is a
      methodological research, developed at the Federal University of Ceara from
      January to March 2012. The construction phases are: the analysis, design and
      development according to the theoretical framework of Galvis-Panqueva. In the
      analysis, objectives, content target audience, the study environment and
      technology infrastructure were delimited. During the design phase the environment
      interface and navigation structure of the course were evaluated. The development
      consisted in the materialization of all that was designed in the previous phase
      Once all three phases of construction of the course were conducted it was
      available in the Virtual Learning Environment SOLAR. The finalproduct of the
      course is presented as support of nursing students and consequently the training
      of future nurses in their care practice on peripheral venipuncture.

PMID- 24015460
TI  - [Consumption of medications, alcohol and smoking in pregnancy and assessment of
      teratogenic risks].
AB  - Medications, alcohol and smoking can cause fetal damage. A cross-sectional study
      was conducted with 326 mothers of the Fortaleza General Hospital to evaluate the
      use of drugs, alcohol and smoking during pregnancy and its relation to
      teratogenic potential in different population characteristics, between 2006 and
      2007. Postpartum women who had their babies in the research site were included
      and those whose babies were not admitted as hospital inpatients were excluded.
      Chi-square tests and t-tests were used in the analysis, with a p value <0.05
      considered significant. 96.6% of the mothers took medications (2.8 drugs/
      pregnancy) and self-medication occurred in 11.3% of the cases. Single women took
      more drugs with high teratogenic potential (p=0.037). 11 cases of fetal
      malformation were observed, five of them were exposed to high teratogenic risks.
      Smoking occurred in 11.3% and alcohol use in 16%. Being single was found to be a
      risk factor for exposure to high teratogenic potential. Quality of prenatal care
      and other sociodemographic variables weren't related to exposure to teratogenic
      risks.

PMID- 24015461
TI  - [Nursing care in the perspective of complexity for nursing professors].
AB  - The complex nursing care is essential for understanding the human being as unique
      and multidimensional. This study aimed at knowing what nursing care means to
      nurse-teachers in the perspective of complexity. It is a qualitative research,
      carried out with seven nurse-teachers of a nursing school from central Rio Grande
      do Sul, Brazil. Data were collected in November 2011, through focus group,from
      three meetings, systematized with themes which considered the objective of this
      study. Discursive text analysis was used for data analysis. Results evinced
      nursing care as unique construction that goes beyond a technical-prescriptive,
      punctual and linear care. It is concluded that nursing care cannot be conceived
      as a reductionist action, but as a unique construction, which involves
      interactions, reflections and self-knowledge.

PMID- 24015462
TI  - [Acceptance of patients with mental illness: a family perspective].
AB  - The aim of this descriptive and qualitative study is to analyse how acceptance of
      mental illness is perceived by family members of the patient and the surrounding
      community. This study was conducted with the help of 10 families of patients with
      mental disorders admitted to the psychiatric emergency unit of the Municipal
      Hospital of Maringa, state of Parana, Brazil. Data were collected from October to
      December 2010, in open interviews and submitted to thematic content analysis,
      resulting in three categories: "Care, a constant requirement", "Living with a
      patient with mental illness: a whirlwind of emotions", "A wall constructed with
      stigma and prejudgement: the need for deconstruction". The conclusion is that an
      understanding of the disease is vital for acceptance of the illness itself and of
      the patient, and that healthcare professionals must remain close to the family to
      provide support, answer queries related to the disease, and help the family to
      face the difficulties of everyday life.

PMID- 24015463
TI  - [Images and representations of the female body in Brazilian magazines].
AB  - This documentary, qualitative, descriptive study has the objective to analyze
      images and representations of the female body and their relation to drug use in
      the content of articles published in four magazines with national circulation
      (Veja, Isto E, Boa Forma, Claudia). The articles selected were submitted to the
      technique of content analysis, with three thematic groups identified: the body as
      an incentive to use drugs; risks to the body resulting from drug use; and the
      search for the perfect body through drug use. The data showed that the media
      reproduces rigid aesthetic standards, exposing women to social and health
      offenses that stimulate drug use, either autonomously or by prescription. The
      search for beauty and the appeal to feminine eroticism, published through the
      communication channels analyzed limit the social importance of women by using
      images that link them to the status of sexual object.

PMID- 24015464
TI  - [Factors associated with the participation of elderly people in group educational
      activities].
AB  - This study sought to characterize the elderly and their participation in group
      educational activities, and to verify the sociodemographic and health factors
      associated with non-participation. It was a cross-sectional survey carried out
      with 2,142 elderly individuals, using descriptive analysis, Student's t-test and
      logistical regression (p<0.05). In both groups, the majority of participants were
      women, 60 - 70 years of age, married with an income of one minimum salary. The
      elderly participants predominately showed 1-4 years of education, with non
      participants 4 - 8. The morbidities most cited by the elderly who participated in
      educational activities were: hypertension and vision problems. Among non
      participants, vision and spinal problems prevailed. In both groups, the greatest
      percentage was 1 - 3 incapacities. The age range of 80 years and above was
      associated with a greater chance of non-participation in activities. It is
      necessary to plan actions that favor participation, thereby contributing to
      monitor their health conditions.

PMID- 24015465
TI  - [Infrastructure and adherence to hand hygiene: challenges to patient safety].
AB  - Considering the importance of hands in the chain of transmission of
      microorganisms, this observational research investigated the material
      infrastructure and compliance of hand hygiene in an intensive care unit in the
      south of Brazil in 2010. The data was collected by direct non-participant
      observation and through the use of self-administered questionnaires to be
      completed by the 39 participants, which was analyzed with the assistance of the
      chi2 Test, descriptive statistics and quantitative discourse analysis. Although
      health professionals overestimate compliance rates, recognize the practice as
      relevant to the prevention of infection and refer there are no impeding factors,
      of the 1,277 opportunities observed, compliance was 26% and significantly lower
      before patient contact and the use of aseptic procedures than after patient
      contact: infrastructure was shown to be deficient. The results indicate risk to
      patient safety, and thus, the planning of corrective actions to promote hand
      washing is relevant.

PMID- 24015466
TI  - [Mothers of visually impaired children: difficult and easy aspects faced in
      care].
AB  - This study aimed to identify the difficult and easy aspects faced by mothers of
      visually impaired (VI) children in their care. It is a descriptive qualitative
      study, developed in the second semester of 2011, with ten mothers of children
      with visual impairment from an Educational Center for the Visually Impaired
      located in southern Brazil. Data were collected by means of semistructured
      interviews and submitted to thematic content analysis. The identified
      difficulties were the lack of knowledge regarding the disease and how to take
      care of the child, the lack of access to health services, overload generated by
      the dependence of the child and lack of support and prejudice within their own
      family. The easy aspects involved the desire for the child's healthy development
      the chance of being in touch with qualified professionals for their education,
      and the contact with other VI children. Therefore, it is important to qualify the
      family for the care of VI children so as to ensure the development of skills and
      competencies enabling them to live with quality.

PMID- 24015467
TI  - [Women in outpatient treatment for alcohol abuse: sociodemographic and clinical
      characteristics].
AB  - Quantitative and descriptive study aimed to identify sociodemographic and
      clinical characteristics of women undergoing outpatient treatment for alcohol
      abuse. Data were collected from medical records of women with alcohol-related
      disorders who were treated at a psychiatric outpatient service We performed a
      reading and descriptive analysis of such data. The sample was composed of 27
      medical records, the average age of women was 50 years, mostly married (59.6%),
      not working (70.4%) with incomplete primary education (70.4%), with an alcoholic
      family (81.5%) and other psychiatric diagnoses (70.3%). Losses physical, social
      and emotional was the most common symptoms resulting from alcohol withdrawal
      syndrome (66.7%), family conflicts (72%) and "sadness" (79.2%). Family violence
      was recorded in 11 records (40.7%). There was low education, unemployment,
      psychiatric comorbidities and the presence of other family members with alcohol
      abuse as common characteristics. We emphasize the importance of professional
      knowledge about the peculiarities of female alcoholism for health activities more
      effective.

PMID- 24015468
TI  - [The tuberculosis control program in Pelotas/RS, Brazil: home contact
      investigations].
AB  - The aim of this study is to evaluate the investigation actions of home contacts
      of tuberculosis (TB) index cases in the Tuberculosis Control Program (TCP) of
      Pelotas/RS - Brazil. This cross-sectional descriptive study was based on data
      from the records of index cases. The sample consisted of 163 contacts of 68
      subjects with pulmonary TB in treatment in the TCP between June and August, 2009.
      These contacts were predominantly female, over 10 years of age and the daughters
      of index cases. The requested examination was a chest radiography and
      bacilloscopy. Active TB was found in 1.8 % of contacts. Results show that
      assistance for TB patients in Pelotas-Brazil, which is centralized in a single
      specialized service, hinders the investigation of home contacts. Primary care is
      required to narrow the gap between professionals and the family, and facilitate
      early diagnosis and interruption of the TB transmission chain in a timely manner.

PMID- 24015469
TI  - [Organization of the health system from the perspective of home care
      professionals].
AB  - The aim of this qualitative case study is to analyze how the health system is
      organized from the perspective of homecare professionals. Data was collected by
      means of semi-structured interviews with seven professionals that provide home
      healthcare services. Content analysis revealed the following empirical
      categories: Perception of home care professionals in relation to their work and
      the health system; Difficulties in articulating the Home Care Program with other
      services of the health system; and, Opportunities to articulate the various
      health services with the Home Care Program. Results indicate that the work
      conducted in the Home Care Program significantly interfaces with other health
      service programs, and is considered important to implement principles of the
      National Health Service.

PMID- 24015470
TI  - [Humanization of healthcare: perception of a nursing team in a neonatal and
      paediatric intensive care unit].
AB  - The humanization of healthcare is one of the key priorities of healthcare
      policies in Brazil, and directly reflects on the attitudes of user, employees and
      managers of health services. The aim of this study was to identify perception of
      the nursing team in terms of humanization of assistance in a neonatal and
      paediatric intensive care unit based on exploratory-descriptive research and a
      qualitative approach. A total of 11 members of a nursing team at the neonatal and
      paediatric intensive care unit of a hospital in southern Brazil participated in
      this study. Data was collected by means of semi structured interviews that were
      subsequently processed according to reference standards of thematic content
      analysis. This analysis resulted in three thematic categories: to humanize is to
      perceive the other as all-providing and all-supportive; bonding and communication
      as humanizing practices; and lack of ambience as a dehumanizing practice. Results
      showed that perception of the nursing team in relation to humanization is
      determined by the actual science and awareness of nursing care rather than
      specific acknowledgement of the National Humanization Policy.

PMID- 24015471
TI  - [Nurse undergraduate students' perception of quality of life].
AB  - The research objective was to know nurse undergraduate students' perception of
      quality of life. A cross-sectional study was conducted from August 2010 to August
      2011 with 56 nursing students of the Faculty of Health Sciences, University of
      Brasilia, Brazil. A specific questionnaire was used (sociodemographic, academic
      and health profile) and the WHOQOL-BREF. Statistical analyzes included a
      description of frequency, central tendency and dispersion measures, and
      comparison between domains. The Psychological and Environment domains were
      assessed as the best and worst scores, respectively. The facets called Thinking,
      learning, memory and concentration, Sleep and rest Energy and fatigue, Activities
      of daily living, Work Capacity, Participation in and opportunities for
      recreation/leisure activities,financial resources and negative feelings were
      affected. The facets with the worst score influenced negatively the quality of
      life for students and might trigger negative feelings such as bad mood,
      desperation anxiety and depression.

PMID- 24015472
TI  - [Patient profile and nursing workload at the nephrology unit].
AB  - Chronic kidney failure (CKF), which is frequently silent, can lead to
      considerable changes in the lives of patients. Depending on the stage,
      hospitalization and hours of nursing care are required to ensure medical and
      surgical treatment. The aim of this descriptive and quantitative study is to
      measure nursing workload at a nephrology unit based on daily application of the
      Nursing Activities Score (NAS) for 47 consecutive days. Patients were mostly
      young male adults in the chronic stage of the disease or admitted for kidney
      transplant. A total of 833 observations were obtained from 62 patients. The
      resulting NAS workload upon admission was 52%, corresponding to 12.5 hours of
      care per patient for 24 hours, which is similar to the workload found in
      intensive care units. This profile allows calculation of nursing work hours
      required for each patient and is a valuable tool for nursing managers when
      determining the number of staff members required to ensure assistance. Other
      studies should be conducted for clinical validation.

PMID- 24015473
TI  - [Nurses' subjectivity production and the decision-making in the process of care].
AB  - This study aimed to understand the relationship between Nurse's production of
      subjectivity and the decision-making in the process of Nursing care. A
      qualitative design of research was conducted. The investigation was carried out
      with twelve nurses who work at the Associacao de Caridade Santa Casa do Rio
      Grande, a hospital located in Rio Grande, RS, Brazil. For data collection, focus
      group technique was used three meetings were conducted in december 2011. The
      results were presented in semantic categories: Capitalist System: maintenance of
      employment bond; Submission System: institutionalized culture and vision of
      society; Nursing Hierarchical System; and Values System: feeling of guilt and
      lack of professional recognition. The capitalist system mediates, mainly, the
      behavior that prevails in the decision-making process in Nursing care.

PMID- 24015474
TI  - [Meaning of living with external fixation for grade III open fracture of lower
      limbs: patient view].
AB  - The present study is aimed to understand the meaning of living with an external
      fixation device for grade III open fractures of the lower limbs from the
      perspective of the patient. The data were collected with six young adults who
      were undergoing outpatient orthopedic treatment in a public hospital in the city
      of Sao Paulo, through semi-structured interviews with open questions, between
      June and August 2010. Seeking to understand the meaning of this experience, we
      have maintained a phenomenological attitude during the analysis, which made it
      possible to reveal the phenomenon "try to live in spite of feeling trapped in a
      cage." Patients said that their personal desire and support from others helped
      them reorganize their lives, despite the several challenges they had to overcome
      to adapt to the fastener attached to their body and the fear of the future and
      doubts about the success of treatment.

PMID- 24015475
TI  - [Expert system to support the decision in topical therapy for venous ulcers].
AB  - Although the treatment of venous ulcers requires a set of specific knowledge, non
      specialist nurses are unaware of the appropriate therapy, which is a concern in
      the topical therapy for these skin lesions. This paper aims to present an expert
      system to support the nursing decision making process in the topical therapy of
      venous ulcers. It is a development research implemented in five stages: system
      modeling, knowledge acquisition, knowledge representation from production rules,
      and system implementation and evaluation. The production rules are presented as
      well as some cases to simulate the expert system behavior, demonstrating the
      viability of its usage in nurse's practice. The system may support the decision
      making about the topical therapy of venous ulcers. However, ulcer evaluation
      should be correctly made, so that the system provides appropriate suggestions,
      allowing better organization and planning assistance.

PMID- 24015476
TI  - [Translation and cross-cultural adaptation of the Edmonton Symptom Assessment
      System for use in Palliative Care].
AB  - The objective of the study was translation and cross-cultural adaptation into
      Brazilian Portuguese of the instrument Edmonton Symptom Assessment System (ESAS
      r). The ESAS-r is a revised version of the instrument ESAS that assesses nine
      symptoms in Palliative Care. This is a methodological study based on a benchmark
      composed of six steps: translation, synthesis, backtranslation, expert committee,
      pre-test and submission of translated version for consideration of the authors.
      As a result changes were made to the title, statements and certain terms to
      ensure adequacy of grammar and vocabulary. In the pre-test the term 'nausea'
      raised doubts, and an additional explanation on this word was suggested.
      Standardization of instrument columns and the replacement of the term
      'depression' for 'sadness' was also recommended. In this study, the ESAS-r
      instrument was translated and adapted to Brazilian Portuguese, and the next step
      will be testing the psychometric properties.

PMID- 24015477
TI  - [Concept maps of the graduate programme in nursing: experience report].
AB  - The conceptual map is considered a strategy that enables the development of
      critical thinking skills. The aim of this article was to evaluate concept maps
      produced by students to obtain an understanding of research projects. This is an
      experience report based on the Special Topic: concept map of the Graduate Program
      in Nursing/Federal University of Paraiba in February/2012. Methodology comprised
      interactive reading of concept maps, installation and use of Cmap Tools software
      and construction of concept maps. Concept evaluation included coherence,
      propositions, clarity of ideas and logical relation between concepts. This
      evaluation of maps revealed consistency among concepts, significant
      relationships, clarity of ideas and logical relationship between the stages of a
      research project. Results showed that the concept map is a valid strategy to
      evaluate the learning-teaching process and can be used for education, research
      and reflection in the nursing practice.

PMID- 24015478
TI  - Functional electrospun poly (lactic acid) scaffolds for biomedical applications:
      experimental conditions, degradation and biocompatibility study.
AB  - The electrospinning technique is a method used to produce nano and microfibers
      using the influence of electrostatic forces. Porous three dimensional networks of
      continuous and interconnected fibers as scaffolds were obtained from a poly
      (lactic acid) solution. The concentration of the polymeric solution, 12.5% m/w,
      as well as the conditions of voltage (V = 11kV) and tip-metallic collector
      distance (H = 13cm) were established to develop these scaffolds through the
      electrospinning process. The characteristics of the scaffolds, such as fiber
      diameter, sintering and the biomimetics of the characteristics of a native extra
      cellular matrix were verified by Scanning Electron Microscopy (SEM). The
      orientation induced in the material as a consequence of the electrospinning
      forces was studied by Differential Scanning Calorimetry (DSC) and X-Ray
      Diffraction (XRD).The same techniques were used to study the hydrolytic
      degradation of samples in a ringer solution (pH = 7-7.4 at 37 degrees C) for 12
      weeks and showed evidences of superficial degradation on the microfibers. The
      suitability of these scaffolds for tissue engineering was studied through the
      primary cell culture of chondrocytes, by observing adhesion and cellular
      proliferation developed during 14 days of assay.

PMID- 24015479
TI  - Challenge of biomechanics.
AB  - The application of mechanics to biology--biomechanics--bears great challenges due
      to the intricacy of living things. Their dynamism, along with the complexity of
      their mechanical response (which in itself involves complex chemical, electrical,
      and thermal phenomena) makes it very difficult to correlate empirical data with
      theoretical models. This difficulty elevates the importance of useful
      biomechanical theories compared to other fields of engineering. Despite inherent
      imperfections of all theories, a well formulated theory is crucial in any field
      of science because it is the basis for interpreting observations. This is all-the
      more vital, for instance, when diagnosing symptoms, or planning treatment to a
      disease. The notion of interpreting empirical data without theory is unscientific
      and unsound. This paper attempts to fortify the importance of biomechanics and
      invigorate research efforts for those engineers and mechanicians who are not yet
      involved in the field. It is not aimed here, however, to give an overview of
      biomechanics. Instead, three unsolved problems are formulated to challenge the
      readers. At the micro-scale, the problem of the structural organization and
      integrity of the living cell is presented. At the meso-scale, the enigma of
      fingerprint formation is discussed. At the macro-scale, the problem of predicting
      aneurysm ruptures is reviewed. It is aimed here to attract the attention of
      engineers and mechanicians to problems in biomechanics which, in the author's
      opinion, will dominate the development of engineering and mechanics in
      forthcoming years.

PMID- 24015480
TI  - Bone tissue formation under ideal conditions in a scaffold generated by a
      reaction-diffusion system.
AB  - The design of porous scaffolds for tissue engineering requires methods to
      generate geometries in order to control the stiffness and the permeability of the
      implant among others characteristics. This article studied the potential of the
      reaction-diffusion systems to design porous scaffolds for bone regeneration. We
      simulate the degradation of the scaffold material and the formation of new bone
      tissue over canal-like, spherical and ellipsoid structures obtained by this
      approach. The simulations show that the degradation and growth rates are affected
      by the form of porous structures. The results have indicated that the proposed
      method has potential as a tool to generate scaffolds with internal porosities and
      is comparable with other methodologies to obtain this type of structures.

PMID- 24015482
TI  - Patient-centric care is all about relationships.

PMID- 24015483
TI  - Contemplating meaningful use. HMT asks industry experts to comment on the most
      important issues related to meeting MU.

PMID- 24015481
TI  - Effect of cartilage endplate on cell based disc regeneration: a finite element
      analysis.
AB  - This study examines the effects of cartilage endplate (CEP) calcification and the
      injection of intervertebral disc (IVD) cells on the nutrition distributions
      inside the human IVD under physiological loading conditions using multiphasic
      finite element modeling. The human disc was modeled as an inhomogeneous mixture
      consisting of a charged elastic solid, water, ions (Na+ and Cl-), and nutrient
      solute (oxygen, glucose and lactate) phases. The effect of the endplate
      calcification was simulated by a reduction of the tissue porosity (i.e., water
      volume faction) from 0.60 to 0.48. The effect of cell injection was simulated by
      increasing the cell density in the nucleus pulposus (NP) region by 50%, 100%, and
      150%. Strain-dependent transport properties (e.g., hydraulic permeability and
      solute diffusivities) were considered to couple the solute transport and the
      mechanical loading. The simulation results showed that nutrient solute
      distribution inside the disc is maintained at a stable state during the day and
      night. The physiological diurnal cyclic loading does not change the nutrient
      environment in the human IVD. The cartilage endplate plays a significant role in
      the nutrient supply to human IVD. Calcification of the cartilage endplate
      significantly reduces the nutrient levels in human IVD. Therefore, in cell based
      therapy for IVD regeneration, the increased nutrient demand as a result of cell
      injection needs to be addressed. Excessive numbers of injected cells may cause
      further deterioration of the nutrient environment in the degenerated disc. This
      study is important for understanding the pathology of IVD degeneration and
      providing new insights into cell based therapies for low back pain.

PMID- 24015485
TI  - Stewards of our own healthcare. Growth of Web-based health records offers
      enormous benefits to consumers.

PMID- 24015484
TI  - Impacts of big data. Potential is huge, so are challenges.

PMID- 24015486
TI  - Incorporating analytics into EMRs. Pushes for quality care are inspiring a deeper
      delving into analytics.

PMID- 24015487
TI  - VAE surveillance helps clinicians improve outcomes. What the CDC's new ventilator
      associated event protocol means.

PMID- 24015488
TI  - N.J. health system saves $1.2 million. How real-time locating systems improve
      efficiency and patient care.

PMID- 24015490
TI  - No internet? No problem. Ensuring access to clinical decision support even when
      internet is spotty or nonexistent.

PMID- 24015489
TI  - Healthcare's new magic wand. Mobile communication is driving innovation and
      improved care.

PMID- 24015491
TI  - Give your EMR eyes and ears. How an RTLS-enabled EMR supports care.

PMID- 24015492
TI  - The messy nature of democracy.

PMID- 24015493
TI  - "If I had an enemy bigger than my apathy, I might have won...".

PMID- 24015494
TI  - OHCA C-section quality initiative follow-up.

PMID- 24015495
TI  - Paclitaxel loaded fibrinogen coated CdTe/ZnTe core shell nanoparticles for
      targeted imaging and drug delivery to breast cancer cells.
AB  - The study aims at the targeted imaging using CdTe/ZnTe core shell QDs and
      delivery of paclitaxel (PTX) loaded fibrinogen coated yellow-QDs (PTX-fib-yellow
      QDs) towards breast cancer cells via the alpha5Beta1-integrins. We developed
      fibrinogen coated different sized CdTe/ZnTe core shell quantum dots of 2-10 nm
      size, which have been prepared by one-pot aqueous-phase approach. The fib-coated
      QDs (fib-coated-QDs) and PTX-fib-yellow-QDs were prepared by two-step
      coacervation technique using CaCl2 as cross-linker. Particle size of fib-coated
      QDs was in between 60-220 nm while PTX-fib-yellow-QDs showed 180 +/- 40 nm. The
      MTT assay confirmed cytocompatibility of fib-coated-QDs on L929 and MCF-7 than
      bare QDs, whereas significant toxicity toward MCF-7 by PTX-fib-yellow-QDs was
      observed. The hemocompatible fib-coated-QDs showed enhanced localization and
      retention toward alpha5beta1-integrins +ve MCF-7 compared to alpha5beta1
      integrins -ve L929 cells. The specific binding of fib-coated-yellow-QDs was
      further confirmed with alpha5beta1-integrins +ve HeLa and alpha5/beta1-integrins 
      ve HT29 cells. Cellular uptake studies revealed localization of PTX-fib-coated
      yellow-QDs inside MCF-7 cells compared to the normal L929 cells. These results
      indicated that fib-coated-QDs could be used for targeted imaging and as a
      suitable "nanocarrier" aiming breast cancer cells.

PMID- 24015496
TI  - Coaxially electrospun core/shell structured poly(L-lactide) acid/chitosan
      nanofibers for potential drug carrier in tissue engineering.
AB  - Biodegradable core/shell structured poly(L-lactide) acid (PLLA)/chitosan (CS)
      nanofibers were fabricated by coaxial electrospinning. PLLA and CS were dissolved
      in dichloromethane and aqueous acetic acid solvents for spinning into core and
      shell layers, respectively. CS of high molecular weight was difficult to spin
      into nanofibers by electrospinning due to its high viscosity, but it was easier
      to achieve by coaxial electrospinning with PLLA. The preparation conditions were
      optimized by changing the ratios of PLLA/CS under different jet voltages. After
      being investigated by scanning electron microscope (SEM), a smooth structure was
      prepared using 2% CS as the shell solution with applied voltage 15 kV.
      Transmission electron microscopy (TEM) study and infrared spectrometry (IR)
      characterization of PLLA/CS nanofibers indicated that the core/shell structure
      was successfully fabricated. Brunauer-Emmett-Teller (BET) surface area and pore
      size distribution exhibited higher capacity of PLLA/CS than PLLA used as drug
      carrier in tissue engineering. The cytocompatibility of nanofibers were evaluated
      by co-cultured with human bone marrow-derived UE7T-13 cells, the 3-(4,5)
      dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) test exhibited good
      proliferation of PLLA/CS for cells. Results of blood compatibility tests showed
      decreased hemolytic ratio and platelets adhesion of PLLA/CS compared with PLLA.
      The results indicated that PLLA/CS nanofibers could be potential drug carrier for
      tissue engineering.

PMID- 24015497
TI  - Fabrication of graphene quantum dots and hexagonal boron nitride nanocomposites
      for fluorescent cell imaging.
AB  - Graphene quantum dots (GQDs) with green fluorescence were incorporated onto
      hexagonal boron nitride sheets (HBN) through electrostatic interaction by using
      poly(diallyldimethylammonium) (PDDA) as the bridge to fabricate the novel
      nanocomposites (HBN-GQDs). The HBN-GQDs nanocomposites exhibited strong green
      fluorescent property, high stability, water solubility, very low cytotoxicity on
      Hela cells. These properties make the HBN-GQDs nanocomposites as good candidate
      materials for biological applications. The results for the imaging of live cells
      indicated that the cell-penetrating HBN-GQDs could be a promising nanoprobe for
      intracellular imaging and therapeutic applications.

PMID- 24015498
TI  - Facile immunotargeting of nanoparticles against tumor antigens using site
      specific biotinylated antibody fragments.
AB  - Nanotechnology is actively being developed for preclinical and clinical oncology
      applications. Nanoparticle-based immunotargeting against tumor antigens with
      antibodies or antibody fragments is designed to increase the nanoparticle
      concentration at the tumor site. However, chemical-based strategies for
      bioconjugating antibody fragments to nanoparticles typically result in a
      functionally heterogeneous population of conjugates due to alteration of amino
      acids within the antigen binding site. The loss of function can be prevented by
      expressing recombinant antibodies that contain a unique bioconjugation site,
      which is isolated from the antigen binding site. Biobodies are antibody fragments
      biosynthetically biotinylated by yeast at a specific biotin acceptor site and
      secreted into the culture supernatant. The high specificity and affinity between
      streptavidin-labeled nanoparticles and soluble biobodies allow self-assembly of
      immunotargeted nanoparticles directly in the yeast culture supernatant. Here, we
      demonstrate the versatility of biobodies for nanoparticle immunotargeting using
      streptavidin-labeled superparamagnetic iron oxide nanoparticles as a general,
      modular scaffold. Biobody-mediated targeting was performed against two antigens
      (mesothelin and TEM1) that are upregulated in solid tumors. The technology for
      biosynthetic biotinylation can be extended to proteins other than antibody
      fragments and adopted by fields outside of oncology for directed modification of
      any streptavidin-functionalized surface.

PMID- 24015499
TI  - Micro-patterned nanowire surfaces encourage directional neural progenitor cell
      adhesion and proliferation.
AB  - Peripheral nerve damage is common in the United States, with an estimated 200,000
      patients treated surgically each year. Autografts, the current gold standard
      treatment, require that the patient trade functionality by transplanting a nerve
      from elsewhere in the body. For this reason, tissue-engineering scaffolds that
      can regenerate nervous tissue and that can direct proliferation need to be
      investigated. In this work we investigated the influence of micro-patterned
      nanowire surfaces on neuronal progenitor cell adhesion and proliferation. We
      created a simple micro-patterning process to create a micro-patterned scaffold
      with regions lacking a nano-topography approximately 60 microns in width bordered
      by regions with a nanowire topography approximately 400 microns in width. We
      hypothesized that neural progenitor cells would preferentially adhere to the
      regions containing the nano-topography and in turn would avoid regions lacking
      the nano-topography. Our results indicate that we can direct neural progenitor
      cell proliferation using this technique. Furthermore, the results show that after
      2 days of culture, cells contacting the boundary have elongated morphology. After
      5 days of culture, quantifying dimensions on the cell aggregates reveals that
      they grow twice as long as they do wide on micro-patterned nanowires when
      compared to controls. These studies suggest that neural progenitor cell growth
      can be directed by simply creating a scaffold with distinct linear regions of
      nano-topography bordered by a smooth, hard, hydrophobic surface.

PMID- 24015500
TI  - 1,25 Dihydroxyvitamin D3 uptake is localized at caveolae and requires caveolar
      function.
AB  - Vitamin D3 is an essential vitamin that has been extensively studied due to its
      potential role as therapeutic for many diseases, including breast cancer.
      Previous research has indicated that calcitriol, the active form of Vitamin D3
      has a negative effect on the metastatic ability of Inflammatory Breast Cancer
      (IBC) cells however the mechanism is not fully understood. The effect of
      calcitriol on IBC cells starting from cellular uptake must be investigated in
      order to understand these therapeutic effects. Calcitriol bound Quantum Dots
      (CalQDs) are a novel nanoparticle conjugated probe that can be used to directly
      examine the distribution, uptake, and signaling of calcitriol in live cells.
      Therefore we used these conjugated probes to directly investigate the uptake of
      calcitriol into live IBC cells. Interestingly, calcitriol uptake was observed to
      decrease when caveolae mediated endocytosis is disrupted. A luciferase assay
      confirmed that caveolae function is necessary; since calcitriol mediated activity
      decreases when caveolae mediated endocytosis is disrupted in IBC cells. In vitro
      examination of the localization of the probe indicated colocalization between
      caveolae and CalQDs. Additionally, Vitamin D Receptor (VDR) colocalization was
      observed with caveolae and calcitriol. This study demonstrates that in IBC cells
      calcitriol enters cells via caveolae mediated endocytosis and that caveolae are
      required for calcitriol to be uptaken at the increased rate.

PMID- 24015502
TI  - Optimization of rate-controlled 17beta-estradiol nanoparticles for cerebral
      ischemia therapy.
AB  - The objective of this study was to prepare and evaluate rate-controlled 17beta
      estradiol nanoparticles (E2-NPs), and then optimize them by central composite
      design (CCD) using a response surface methodology (RSM). The E2-NPs were designed
      for cerebral ischemia therapy and prepared by oil-in-water (o/w) emulsion by
      mixing E2 and phosphatidylcholine, cross-linking of the bovine serum albumin
      (BSA) wall material with glutaraldehyde, and subsequently creating a
      biodegradable coating shell with L-arginine. In two-factor, five-level CCD, the
      independent variables were the pH value of the aqueous phase (X1) and the amount
      of glutaraldehyde (X2). The optimal formulation of the E2-NPs was developed from
      the response equations of each fitted model. The optimal E2-NPs particle size was
      92.4 +/- 1.4 nm, and its cumulative release in 4.0 h (therapeutic window for
      stroke) was 71.17 +/- 0.24%, with a zero-order release model of 24 h. The
      preparation and testing of the optimal formulation showed a good correlation
      between the predicted and observed values. In addition, a brain microdialysis
      study demonstrated that the E2-NPs had the ability to penetrate the blood-brain
      barrier and clearly increase and maintain the drug concentration in the brain
      over 12 h. Furthermore, the E2-NPs reduced brain infarct size in rats with middle
      cerebral artery occlusion (MCAO)-induced stroke. These results suggest that rate
      controlled E2-NPs increase the efficacy of E2 for ischemic stroke therapy.

PMID- 24015501
TI  - Antibacterial gold nanoparticles-biomass assisted synthesis and characterization.
AB  - Xylose is a natural monosaccharide found in biomass such as straw, pecan shells,
      cottonseed hulls, and corncobs. Using this monosaccharide, we report the facile,
      green synthesis and characterization of stable xylose encapsulated gold
      nanoparticles (Xyl-GNPs) with potent antibacterial activity. Xyl-GNPs were
      synthesized using the reduction property of xylose in an aqueous solution
      containing choloraurate anions carried out at room temperature and atmospheric
      pressure. These nanoparticles were stable and near spherical in shape with an
      average diameter of 15 +/- 5 nm. Microbiological assay results showed the
      concentration dependent antibacterial activity of these particles against both
      Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus epidermidis)
      bacteria. Thus the facile, environmentally friendly Xyl-GNPs have many potential
      applications in chemical and biomedical industries, particularly in the
      development of antibacterial agents in the field of biomedicine.

PMID- 24015503
TI  - In vivo delivery of Atoh1 gene to rat cochlea using a dendrimer-based
      nanocarrier.
AB  - Gene therapy is a promising clinical solution to hearing loss. However suitable
      gene carriers for the auditory system are currently unavailable. Given the unique
      structure of the inner ear, the route of delivery and gene transfer efficiency
      are still not optimal at present. This study presented a non-viral delivery
      system of in vivo delivery of Atoh1 gene (a potentially therapeutic gene for
      hearing loss) to rat cochlea. We treated polyamidoamine (PAMAM) dendrimers by
      activating and modifying with Na-carboxymethyl-beta-cyclodextrins (CM-beta-CD) in
      sequence. A novel gene carrier (CM-beta-CD modified activated PAMAM dendrimers,
      CMAP) was then constructed. CMAP nanoparticles could bind pRK5-Atoh1-EGFP
      plasmids to form vector-DNA complexes (dendriplexes) with a mean particle size of
      132 +/- 20 nm and zeta potential of 31 +/- 3 mV. These dendriplexes were locally
      applied on the round window membrane and delivered to the inner ear by passive
      gradient permeation. Results showed that the Atoh1 gene was successfully
      transferred into the cells as indicated by the green fluorescence detected in the
      inner ear. A relatively selective gene transfer with high efficiency was achieved
      in the auditory hair cells but not much in other cell types in the cochlea.
      Auditory brainstem response was determined seven days after inoculation,
      indicating good tolerance. This approach may provide a novel tool for inner ear
      gene therapy and initiate the applications of biomaterials to treat auditory
      disorders.

PMID- 24015504
TI  - Gold nanoparticles induce nanostructural reorganization of VEGFR2 to repress
      angiogenesis.
AB  - The inhibition of the binding between VEGFs and their receptors reduces
      angiogenesis and retards tumor growth. Owing to the large amount of antibodies
      required, the antibody-based anti-angiogenic drug remains limited. Gold
      nanoparticles (AuNPs) displayed excellent biocompatibility, low toxicity and anti
      angiogenic effect, but the mechanism of anti-angiogenesis was unknown. Here, the
      antitumor effects of a well-dispersed AuNPs, specifically regarding its influence
      on VEGF signaling, were examined mechanistically. The effects of AuNPs on the
      interaction of VEGF with its receptor, VEGFR2 were observed using near-field
      scanning optical microscopy/quantum dot (NSOM/QD) imaging. We found AuNPs can
      reduce VEGF165-induced VEGFR2 and AKT phosphorylation. Furthermore, the antitumor
      effects of AuNPs were determined using xenograft and ascites model. AuNPs
      inhibited VEGF165-VEGFR2 interaction and suppressed the formation of nanodomains
      of VEGFR2 on the HUVEC. As determined by CD34 immunhistochemistry, AuNPs reduced
      angiogenesis in a liver tumor nude mice model, as observed by a decreased
      microvascular density in liver tumor sections and reduced the tumor weight and
      volume. In addition, AuNPs inhibited ascites formation in mice. Taken together,
      this study provides new insights into nanomaterial-based antitumor drug
      development.

PMID- 24015505
TI  - Biological characteristics of mesenchymal stem cells grown on different
      topographical nanofibrous poly-L-lactide meshes.
AB  - The nanotopographical features of artificial scaffolds have complex effects on
      the biological characteristics of stem cells. They influence cell adhesion,
      spreading, proliferation, and differentiation; however we have limited knowledge
      on how these processes occur under nanotopographical cues. In this study, two
      kinds of electrospun nanofibrous meshes with different fiber arrangements
      (totally non-woven and lattice-like) were fabricated and used for in vitro
      culture of mesenchymal stem cells (MSCs). By comparing the characteristic marks
      related to osteogenic differentiation, we found that with prolonged culture time,
      osteopontin (OPN), osteocalcin (OCN) and alkaline phosphatase (ALP), as well as
      related genes (Runx2 and Colla genes), were all expressed at higher levels on
      lattice-like nanofibrous meshes than on non-woven ones. These results indicated
      that the lattice-like nanofibrous mesh activated the osteogenic differentiation
      of MSCs owing to changes in cell morphology directed by nanofiber orientations.
      Compared with pure non-woven nanofibrous meshes, lattice-like ones possessed a
      combined structure of parallel, magnetic-line-like, and non-woven regions. MSCs
      adhering onto them had upregulated expression levels of integrin subunits a5 and
      b1, and activated downstream signaling pathways of Ras homolog gene family member
      A (RhoA) and extracellular signal-regulated kinase (ERK). When the specific
      inhibitors PD98059 and Y27632 were used to inhibit phosphorylated ERK and p160
      ROCKII activity, respectively, F-actin became disordered and the expression level
      of Runx2 was downregulated. Thus, we concluded that the scaffold nanotopography
      may modulate the microenvironment of MSCs and promote their osteogenic
      differentiation through the RhoA and ERK signaling pathways. These findings
      provided valuable information on the selection of artificial matrices suitable
      for MSCs application in bone tissue engineering.

PMID- 24015506
TI  - Enrichment of malaria parasites by antibody immobilized magnetic nanoparticles.
AB  - The simple and less expensive technique based on magnetic nanoparticles (MNPs)
      was developed for separation of malaria parasites containing specific antigens.
      The carboxylated MNPs were chemically bound with anti-P. falciparum IgG
      antibodies (Ab-MNPs) purified from the plasma of malaria patients and then used
      for removal of P. falciparum malaria-infected erythrocytes from other non
      infected blood cells in malaria culture at a given percent parasitemia. The
      results from optical microscope showed that all blood stages parasites, i.e.,
      ring, trophozoite and schizont, could be separated from other blood components
      with high purity (> or = 95%) and yield of 33.5% (the early stages of ring and
      trophozoite:the schizont stage were 1:1.34). Highly specific interaction between
      Ab-MNPs and the P. falciparum malaria infected erythrocytes was confirmed by
      scanning electron microscope. When compared to the centrifugation with Percoll
      gradient and depletion by sorbitol lysis which are specific to the mature and the
      ring stages, respectively, our technique would be more useful for production of
      high quality of parasites to use in malaria pathogenesis or immunological
      studies, and in detection techniques.

PMID- 24015507
TI  - A new amperometric glucose biosensor based on one-step electrospun poly(vinyl
      alcohol)/chitosan nanofibers.
AB  - In this work, a new glucose amperometric biosensor was developed by directly
      electrospinning poly(vinyl alcohol)/chitostan nanofibers on the surface of the
      platinum electrode, in which glucose oxidase (GOD) was effectively immobilized in
      nanofibers by encapsulation. After been cross-linked in glutaraldehyde vapor and
      modified with a thin nafion film, the nanofibers (PVA/chitosan/GOD)/nafion
      electrode was used for glucose amperometric measurements. The electrospun
      nanofibrous enzyme membrane served as a better sensing element than the casing
      one due to the unique properties of nanofibers such as the special three
      dimensional network structure, large pores, high porosity, and large surface to
      volume ratios. The as-prepared biosensor showed a wide linear calibration range,
      low detection limit, and low apparent Michaelis-Menten constant in the glucose
      determination. The stability, reproducibility and anti-interference capability of
      biosensor were also presented. Furthermore, the new biosensor was successfully
      applied to detect glucose in human serum samples.

PMID- 24015508
TI  - Protein-bearing cubosomes prepared by liquid precursor dilution: inner ear
      delivery and pharmacokinetic study following intratympanic administration.
AB  - This study aims to design self-assembled cubic liquid crystalline nanoparticles
      (cubosomes) to enhance inner ear bioavailability of earthworm fibrinolytic enzyme
      (EFE). The cubosomes were prepared using a liquid precursor mixture containing
      glyceryl monooleate, hydrotrope propylene glycol, and F127 as stabilizer.
      Submicron-size particles (100 nm to 200 nm) with slight negative charge formed
      spontaneouly upon dilution of the liquid precursors. Small-angle X-ray scattering
      (SAXS) results demonstrated that the formation of cubsomses largely depended on
      the hydration level of liquid precursor and the encapsulation of highly
      hydrophilic EFE induced the phase transition of the cubosome. The encapsulatoin
      efficiency of EFE in cubosomes was 79.6% and their cubic ultrastructure were
      confirmed by TEM. In vitro cell toxicity results showed that the viability of
      L929 cells decreased by increasing the concentration of nanoparticles. Octadecyl
      rhodamine B chloride (R18) labeled cubosomes were identified in the basal turn of
      the scala tympani and middle portion of the cochlea after 30 min post
      intratympanic administration, indicating that cubosomes could permeate through
      the RWM. The AUC(0 h-24 h) of EFE administrated as EFE cubosomes was 2.6-fold in
      cochlear fluid compared to those applied by free drug via the intratympanic
      route. In conclusion, self-assembled liquid crystalline nanoparticles provide a
      promising protein vehicle for effective inner ear drug delivery.

PMID- 24015509
TI  - Applications of ZnO nanoflowers as antimicrobial agents for Escherichia coli and
      enzyme-free glucose sensor.
AB  - Well-crystalline ZnO nanoflowers were prepared by a facile solution process and
      their applications as an antimicrobial agent against Escherichia coli and enzyme
      free glucose sensor have been studied. The morphological, structural,
      compositional, and optical properties of ZnO nanoflowers were characterized by
      various techniques, which confirmed the well-crystalline wurtzite hexagonal
      phase. The minimum inhibitory concentration of ZnO nanoflowers for inhibiting the
      growth of Escherichia coli was found to be 25 microg/ml. ZnO nanoflowers were
      also tested as an efficient electron mediator for the fabrication of highly
      sensitive non-enzymatic glucose sensor, which exhibited a high sensitivity of 
      411 microA M(-1) cm(-2) and detection limit of -1.25 mM with a quick response
      time of -10.0 s. The presented studies showed that ZnO nanomaterials can be
      efficiently used as an antimicrobial agent and a highly sensitive non-enzymatic
      glucose sensor.

PMID- 24015510
TI  - Synergistic effects of algal overgrowth and corallivory on Caribbean reef
      building corals.
AB  - Indirect biotic interactions play a crucial role in structuring ecological
      communities, but many of these interactions have not been explored. Algal
      competition and corallivory are two major stressors contributing to the decline
      of coral reefs. Here, we provide the first evidence of algal-induced corallivory
      and synergistic effects between the two stressors on corals. When corals
      (Montastraeafaveolata) were placed in contact with algae (Halimeda opuntia)
      together with corallivorous fireworms (Hermodice carunculata) in aquaria, corals
      suffered high tissue mortality. This mortality was reduced in the presence of
      algae only, and no mortality occurred in the presence of fireworms only or when
      excluding both algae and fireworms. These findings were supported by field
      observations showing a predominance of fireworms inside algae contacting live
      corals, and by an in situ experiment demonstrating higher coral mortality in
      contact with algae left undisturbed than with algae from which all mobile
      epifauna were periodically removed. Among the main contributing mechanisms, we
      suggest that algal contact produces decaying coral tissue that attracts the
      corallivore and enhances its aggregation behavior. Our study demonstrates an
      indirect effect pathway by which algae can impact corals, which shares
      similarities with the classic models of apparent competition and habitat
      facilitation.

PMID- 24015511
TI  - Parsing handling time into its components: implications for responses to a
      temperature gradient.
AB  - The functional response is a key element of predator-prey interactions, and
      variations in its parameters influence interaction strength and population
      dynamics. Recent studies have used the equation of the metabolic theory of
      ecology (MTE) to quantify the effect of temperature on the parameter Th, called
      "handling time," and then predict the responses of predators and communities to
      climate change. However, our understanding of the processes behind Th and how
      they vary with temperature remains limited. Using a ladybeetle-aphid system, we
      compared estimates of Th to direct observations of handling time across a
      temperature gradient. We found estimated Th values to be greater than observed Th
      values, suggesting that predation rate is not limited by the time available for
      handling prey. We next estimated the corrected digestion time, i.e., digestion
      time corrected for gut capacity, by subtracting observed to estimated Th values.
      We finally plotted the relationships between temperature and handling or
      digestion rates. As predicted by MTE, the corrected digestion rate increased
      exponentially with warming whereas, in contrast to MTE prediction, the
      relationship between handling rate and temperature was hump shaped. The parameter
      Th is thus confusing because it combines handling and digestive processes that
      have different thermal responses. This may explain why general patterns in the
      relationship between Th and temperature have been difficult to identify in
      previous studies.

PMID- 24015512
TI  - The role of transient dynamics in stochastic population growth for nine perennial
      plants.
AB  - Most populations exist in variable environments. Two sets of theory have been
      developed to address this variability. Stochastic dynamics focus on variation in
      population growth rates based on random differences in vital rates such as
      growth, survival, and reproduction. Transient dynamics focus on short-term,
      deterministic responses to changes in the stage distribution of individuals.
      These processes are related: demographic variation shifts stage structures,
      producing transient responses, which then contribute to the overall variability
      of population growth rate. The relative contributions of vital rates vs.
      transient responses to stochastic dynamics, and the implications for transient
      analyses, are unclear. This study explores the role of transient responses in
      stochastic dynamics of nine perennial plant species. Across the species,
      transient responses contributed more on average to variability in annual
      population growth rates than did variation in vital rates alone. Transient
      potential of an average matrix was indicative of the contribution of transient
      dynamics, although these metrics varied greatly across years. Transient responses
      were often in the opposite direction as demographic variation, suggesting that
      transient dynamics may at times have a buffering effect on populations. Overall,
      transient dynamics had an important role in modulating environmental variation,
      with implications for both processes in understanding stochastic dynamics.

PMID- 24015513
TI  - Sensitivity of grassland plant community composition to spatial vs. temporal
      variation in precipitation.
AB  - Climate gradients shape spatial variation in the richness and composition of
      plant communities. Given future predicted changes in climate means and
      variability, and likely regional variation in the magnitudes of these changes, it
      is important to determine how temporal variation in climate influences temporal
      variation in plant community structure. Here, we evaluated how species richness,
      turnover, and composition of grassland plant communities responded to interannual
      variation in precipitation by synthesizing long-term data from grasslands across
      the United States. We found that mean annual precipitation,(MAP) was a positive
      predictor of species richness across sites, but a positive temporal relationship
      between annual precipitation and richness was only evident within two sites with
      low MAP. We also found higher average rates of species turnover in dry sites that
      in turn had a high proportion of annual species, although interannual rates of
      species turnover were surprisingly high across all locations. Annual species were
      less abundant than perennial species at nearly all sites, and our analysis showed
      that the probability of a species being lost or gained from one year to the next
      increased with decreasing species abundance. Bray-Curtis dissimilarity from one
      year to the next, a measure of species composition change that is influenced
      mainly by abundant species, was insensitive to precipitation at all sites. These
      results suggest that the richness and turnover patterns we observed were driven
      primarily by rare species, which comprise the majority of the local species pools
      at these grassland sites. These findings are consistent with the idea that short
      lived and less abundant species are more sensitive to interannual climate
      variability than longer-lived and more abundant species. We conclude that, among
      grassland ecosystems, xeric grasslands are likely to exhibit the greatest
      responsiveness of community composition (richness and turnover) to predicted
      future increases in interannual precipitation variability. Over the long-term,
      species composition may shift to reflect spatial patterns of mean precipitation;
      however, perennial-dominated systems will be buffered against rising interannual
      variation, while systems that have a large number of rare, annual species will
      show the greatest temporal variability in species composition in response to
      rising interannual variability in precipitation.

PMID- 24015514
TI  - Biodiversity simultaneously enhances the production and stability of community
      biomass, but the effects are independent.
AB  - To predict the ecological consequences of biodiversity loss, researchers have
      spent much time and effort quantifying how biological variation affects the
      magnitude and stability of ecological processes that underlie the functioning of
      ecosystems. Here we add to this work by looking at how biodiversity jointly
      impacts two aspects of ecosystem functioning at once: (1) the production of
      biomass at any single point in time (biomass/area or biomass/ volume), and (2)
      the stability of biomass production through time (the CV of changes in total
      community biomass through time). While it is often assumed that biodiversity
      simultaneously enhances both of these aspects of ecosystem functioning, the joint
      distribution of data describing how species richness regulates productivity and
      stability has yet to be quantified. Furthermore, analyses have yet to examine how
      diversity effects on production covary with diversity effects on stability. To
      overcome these two gaps, we reanalyzed the data from 34 experiments that have
      manipulated the richness of terrestrial plants or aquatic algae and measured how
      this aspect of biodiversity affects community biomass at multiple time points.
      Our reanalysis confirms that biodiversity does indeed simultaneously enhance both
      the production and stability of biomass in experimental systems, and this is
      broadly true for terrestrial and aquatic primary producers. However, the strength
      of diversity effects on biomass production is independent of diversity effects on
      temporal stability. The independence of effect sizes leads to two important
      conclusions. First, while it may be generally true that biodiversity enhances
      both productivity and stability, it is also true that the highest levels of
      productivity in a diverse community are not associated with the highest levels of
      stability. Thus, on average, diversity does not maximize the various aspects of
      ecosystem functioning we might wish to achieve in conservation and management.
      Second, knowing how biodiversity affects productivity gives no information about
      how diversity affects stability (or vice versa). Therefore, to predict the
      ecological changes that occur in ecosystems after extinction, we will need to
      develop separate mechanistic models for each independent aspect of ecosystem
      functioning.

PMID- 24015515
TI  - Phenological cues drive an apparent trade-off between freezing tolerance and
      growth in the family Salicaceae.
AB  - With increasing concern about the ecological consequences of global climate
      change, there has been renewed interest in understanding the processes that
      determine species range limits. We tested a long-hypothesized trade-off between
      freezing tolerance and growth rate that is often used to explain species range
      limits. We grew 24 willow and poplar species (family Salicaceae) collected from
      across North America in a greenhouse common garden under two climate treatments.
      Maximum entropy models were used to describe species distributions and to
      estimate species-specific climate parameters. A range of traits related to
      freezing tolerance, including senescence, budburst, and susceptibility to
      different temperature minima during and after acclimation were measured. As
      predicted, species from colder climates exhibited higher freezing tolerance and
      slower growth rates than species from warmer climates under certain environmental
      conditions. However, the average relative growth rate (millimeters per meter per
      day) of northern species markedly increased when a subset of species was grown
      under a long summer day length (20.5 h), indicating that genetically based day
      length cues are required for growth regulation in these species. We conclude that
      the observed relationship between freezing tolerance and growth rate is not
      driven by differences in species' intrinsic growth capacity but by differences in
      the environmental cues that trigger growth. We propose that the coordinated
      evolution of freezing tolerance and growth phenology could be important in
      circumscribing willow and poplar range limits and may have important implications
      for species' current and future distributions.

PMID- 24015516
TI  - Landscape-scale density-dependent recruitment of oaks in planted forests: more is
      not always better.
AB  - Plant colonization studies usually address density-dependent processes in the
      narrow sense of recruitment constraints due to negative density-dependent seed
      and seedling mortality. However, complex density-dependent effects may be
      involved in additional stages of the recruitment process. We hypothesized that
      seed arrival and seedling establishment are influenced by density dependence
      acting at small scales at the site of colonization, and at larger scales as a
      function of the colonizing species' landscape abundance. These hypotheses were
      tested in a study of colonization of pine forests by oaks in a heterogeneous
      Mediterranean landscape. Maximum-likelihood models show that density effects
      switch from positive to negative along the range of landscape-scale oak seed
      source abundance. Contrary to expectations, high seed source densities limited
      oak recruitment, suggesting a landscape-scale Janzen-Connell effect. We propose a
      range of mechanisms that generate positive or negative density dependence during
      colonization, resulting in nonlinear density-dependent feedbacks that can
      generate unexpected colonization patterns.

PMID- 24015517
TI  - Fire-mediated pathways of stand development in Douglas-fir/ western hemlock
      forests of the Pacific Northwest, USA.
AB  - Forests dominated by Douglas-fir and western hemlock in the Pacific Northwest of
      the United States have strongly influenced concepts and policy concerning old
      growth forest conservation. Despite the attention to their old-growth
      characteristics, a tendency remains to view their disturbance ecology in
      relatively simple terms, emphasizing infrequent, stand-replacing (SR) fire and an
      associated linear pathway toward development of those old-growth characteristics.
      This study uses forest stand- and age-structure data from 124 stands in the
      central western Cascades of Oregon to construct a conceptual model of stand
      development under the mixed-severity fire regime that has operated extensively in
      this region. Hierarchical clustering of variables describing the age
      distributions of shade-intolerant and shade-tolerant species identified six
      groups, representing different influences of fire frequency and severity on stand
      development. Douglas-fir trees > 400 years old were found in 84% of stands, yet
      only 18% of these stands (15% overall) lack evidence of fire since the
      establishment of these old trees, whereas 73% of all stands show evidence of at
      least one non-stand-replacing (NSR) fire. Differences in fire frequency and
      severity have contributed to multiple development pathways and associated
      variation in contemporary stand structure and the successional roles of the major
      tree species. Shade-intolerant species form a single cohort following SR fire, or
      up to four cohorts per stand in response to recurring NSR fires that left living
      trees at densities up to 45 trees/ha. Where the surviving trees persist at
      densities of 60-65 trees/ha, the postfire cohort is composed only of shade
      tolerant species. This study reveals that fire history and the development of old
      growth forests in this region are more complex than characterized in current
      stand-development models, with important implications for maintaining existing
      old-growth forests and restoring stands subject to timber management.

PMID- 24015518
TI  - Comparison of plant preference hierarchies of male and female moths and the
      impact of larval rearing hosts.
AB  - Selection of a suitable host plant is essential for the fitness of herbivorous
      insects. For polyphagous insects the underlying proximate mechanisms for host
      plant selection, including phenotypic plasticity, remain only partially
      understood. We established an experimental protocol evaluating preferences to
      five plant species in males and females of the polyphagous moth Spodoptera
      littoralis. Female preference hierarchies were assessed by oviposition decisions;
      those of males were assessed by the attraction to female sex pheromones in
      background odors of different plant species. The experiments revealed clear
      preference hierarchies in both males and females, which were partly overlapping
      in spite of the different behavioral contexts of the respective assays.
      Furthermore, we demonstrated strong effects of the larval rearing host on adult
      plant preference, where the larval host plant species was generally elevated to
      the most preferred plant in both sexes, without otherwise affecting the overall
      preference hierarchy. Our results suggest that both sexes are involved in host
      plant choice and that experience-based convergent intersexual plant preferences
      may confer selective advantages. The host plant choice is guided by a stable
      plant preference hierarchy, which can be modified by the larval rearing host,
      permitting fast adaptation to variation in local conditions and to novel
      environments. It may also provide a mechanism for reducing costs associated with
      polyphagy by functional plasticity in plant choice.

PMID- 24015519
TI  - Insect herbivores change the outcome of plant competition through both inter- and
      intraspecific processes.
AB  - Insect herbivores can affect plant abundance and community composition, and
      theory suggests that herbivores influence plant communities by altering
      interspecific interactions among plants. Because the outcome of interspecific
      interactions is influenced by the per capita competitive ability of plants,
      density dependence, and intrinsic rates of increase, measuring herbivore effects
      on all these processes is necessary to understand the mechanisms by which
      herbivores influence plant communities. We fit alternative competition models to
      data from a response surface experiment conducted over four years to examine how
      herbivores affected the outcome of competition between two perennial plants,
      Solidago altissima and Solanum carolinense. Within a growing season, herbivores
      reduced S. carolinense plant size but did not affect the size of S. altissima,
      which exhibited compensatory growth. Across seasons, herbivores did not affect S.
      carolinense density or biomass but reduced both the density and population growth
      of S. altissima. The best-fit models indicated that the effects of herbivores
      varied with year. In some years, herbivores increased the per capita competitive
      effect of S. altissima on S. carolinense; in other years, herbivores influenced
      the intrinsic rate of increase of S. altissima. We examined possible herbivore
      effects on the longer-term outcome of competition (over the time scale of a
      typical old-field habitat), using simulations based on the best-fit models. In
      the absence of herbivores, plant coexistence was observed. In the presence of
      herbivores, S. carolinense was excluded by S. altissima in 72.3% of the
      simulations. We demonstrate that herbivores can influence the outcome of
      competition through changes in both per capita competitive effects and intrinsic
      rates of increase. We discuss the implications of these results for ecological
      succession and biocontrol.

PMID- 24015520
TI  - Insect herbivores, chemical innovation, and the evolution of habit specialization
      in Amazonian trees.
AB  - Herbivores are often implicated in the generation of the extraordinarily diverse
      tropical flora. One hypothesis linking enemies to plant diversification posits
      that the evolution of novel defenses allows plants to escape their enemies and
      expand their ranges. When range expansion involves entering a new habitat type,
      this could accelerate defense evolution if habitats contain different assemblages
      of herbivores and/or divergent resource availabilities that affect plant defense
      allocation. We evaluated this hypothesis by investigating two sister habitat
      specialist ecotypes of Protium subserratum (Burseraceae), a common Amazonian tree
      that occurs in white-sand and terra firme forests. We collected insect herbivores
      feeding on the plants, assessed whether growth differences between habitats were
      genetically based using a reciprocal transplant experiment, and sampled multiple
      populations of both lineages for defense chemistry. Protium subserratum plants
      were attacked mainly by chrysomelid beetles and cicadellid hemipterans.
      Assemblages of insect herbivores were dissimilar between populations of ecotypes
      from different habitats, as well as from the same habitat 100 km distant.
      Populations from terra firme habitats grew significantly faster than white-sand
      populations; they were taller, produced more leaf area, and had more chlorophyll.
      White-sand populations expressed more dry mass of secondary compounds and
      accumulated more flavone glycosides and oxidized terpenes, whereas terra firme
      populations produced a coumaroylquinic acid that was absent from white-sand
      populations. We interpret these results as strong evidence that herbivores and
      resource availability select for divergent types and amounts of defense
      investment in white-sand and terra firme lineages of Protium subserratum, which
      may contribute to habitat-mediated speciation in these trees.

PMID- 24015521
TI  - Testing the stress gradient hypothesis in herbivore communities facilitation
      peaks at intermediate nutrient levels.
AB  - The role of positive interactions in structuring plant and animal communities is
      increasingly recognized, but the generality of current theoretical models has
      remained practically unexplored in animal communities. The stress gradient
      hypothesis predicts a linear increase in the intensity of facilitation as
      environmental conditions become increasingly stressful, whereas other theoretical
      models predict a maximum at intermediate environmental stress. We tested how
      competition and facilitation between herbivores change over a manipulated
      gradient of nutrient availability. We studied the effect of grazing by pond
      snails (Lymnaea stagnalis L.) as bulk grazers on aquatic caterpillars (Acentria
      ephemerella Denis and Schiffermuller) as small specialist grazers along an
      experimental gradient of environmental nutrient concentration. Higher nutrient
      levels increased overall total plant biomass but induced a shift toward dominance
      of filamentous algae at the expense of macrophytes. Facilitation of caterpillars
      by snail presence peaked at intermediate nutrient levels. Both caterpillar
      biomass and caterpillar grazing on macrophytes were highest at intermediate
      nutrient levels. Snails facilitated caterpillars possibly by removing filamentous
      algae and increasing access to the macrophyte resource, whereas they did not
      affect macrophyte biomass or C: nutrient ratios, a measure of food quality. We
      conclude that competition and facilitation in herbivore communities change along
      nutrient availability gradients that affect plant biomass and community
      composition. Understanding how interspecific interactions may change in strength
      and direction along environmental gradients is important to predict how the
      diversity and structure of communities may respond to the introduction or removal
      of herbivore species in ecosystems.

PMID- 24015522
TI  - Extinction cascades partially estimate herbivore losses in a complete Lepidoptera
      -plant food web.
AB  - The loss of species from an ecological community can have cascading effects
      leading to the extinction of other species. Specialist herbivores are highly
      diverse and may be particularly susceptible to extinction due to host plant loss.
      We used a bipartite food web of 900 Lepidoptera (butterfly and moth) herbivores
      and 2403 plant species from Central Europe to simulate the cascading effect of
      plant extinctions on Lepidoptera extinctions. Realistic extinction sequences of
      plants, incorporating red-list status, range size, and native status, altered
      subsequent Lepidoptera extinctions. We compared simulated Lepidoptera extinctions
      to the number of actual regional Lepidoptera extinctions and found that all
      predicted scenarios underestimated total observed extinctions but accurately
      predicted observed extinctions attributed to host loss (n = 8, 14%). Likely, many
      regional Lepidoptera extinctions occurred for reasons other than loss of host
      plant alone, such as climate change and habitat loss. Ecological networks can be
      useful in assessing a component of extinction risk to herbivores based on host
      loss, but further factors may be equally important.

PMID- 24015523
TI  - Context-dependent amphibian host population response to an invading pathogen.
AB  - Amphibian chytridiomycosis, caused by the chytrid fungus Batrachochytrium
      dendrobatidis (Bd), is an emerging infectious disease that widely threatens
      amphibian biodiversity. However, population-level outcomes following the
      introduction of the pathogen are highly context dependent and are mediated by a
      broad suite of biotic and abiotic variables. Here, we examine the effect of the
      introduction of Bd on native island populations of the IUCN red-listed amphibian
      species Alytes muletensis, the Mallorcan midwife toad. We show that the outcome
      of pathogen introduction is not only dependent on biotic factors, but is also
      dependent on environmental factors that vary across local scales. Our
      experimental infections confirm that the genotype of Bd occurring on Mallorca is
      hypovirulent in A. muletensis when compared against the lineage found occurring
      on mainland Iberia. Long-term population data show that A. muletensis populations
      on the island are increasing overall, but trends in highly infected populations
      are conflicting. We use mathematical models and field data to demonstrate that
      this divergence in population response to infection can be explained by local
      environmental differences between infected sites, whereas pathogen genetics, host
      genetics, and intrinsic epidemiological dynamics driven by fungal load are less
      likely to be the cause of these differing population trajectories. Our results
      illustrate the need to take into account the appropriate environmental scale and
      context when assessing the risk that an emerging pathogen presents to a naive
      population or species.

PMID- 24015524
TI  - Variation in adult body mass of roe deer: early environmental conditions
      influence early and late body growth of females.
AB  - There is increasing evidence that environmental conditions experienced early in
      life can markedly affect an organism's life history, but the pathways by which
      early environment influences adult phenotype are poorly known. We used long-term
      data from two roe deer (Capreolus capreolus) populations (Chize and Trois
      Fontaines, France) to investigate the direct and indirect (operating through fawn
      body mass) effects of environmental conditions during early life on adult body
      mass. We found that environmental conditions (population size and spring
      temperatures) around birth influenced body mass of adult females through both
      direct and indirect effects in both populations. The occurrence of direct effects
      means that, for a given fawn body mass, adult female mass decreases with adverse
      conditions in early life. In contrast, we found no evidence for direct effects of
      early-life conditions on adult body mass of males, suggesting the existence of
      sex-specific long-term responses of body mass to stressful early conditions. Our
      results provide evidence that early environmental conditions influence the adult
      phenotype through persistent effects over the body development in wild mammal
      populations.

PMID- 24015525
TI  - Nitrogen allocation to offspring and milk production in a capital breeder.
AB  - Nitrogen (N) is a limiting nutrient for many herbivores, especially when plant
      availability and N content are low during the period of maternal investment,
      which is common for arctic ungulates. We used natural abundance of N isotopes to
      quantify allocation of maternal nitrogen to neonatal calves and milk in wild
      migratory caribou (Rangifer tarandus). We contrasted female-calf pairs from two
      herds in northern Quebec/Labrador, Canada: Riviere-George herd (RG; low
      population size with heavy calves) and the Riviere-aux-Feuilles herd (RAF; high
      population size and small calves). We assessed whether females of both herds
      relied on body protein or dietary N to produce the neonatal calf and milk at
      calving and weaning. Female caribou of both herds relied mostly on body N for
      fetal development. RAF females allocated less body N to calves than did RG
      females (92% vs. 95% of calf N), which was consistent with the production of
      calves that were 8% smaller in RAF than in RG. Allocation of body N to milk was
      also high for both herds, similar at calving for RAF and RG females (88% vs. 91%
      of milk N, respectively), but lower in RAF than RG females (95% vs. 99% of milk
      N) at weaning, which was consistent with a small but significantly greater
      reliance on dietary N supplies to support milk production at weaning. Female
      caribou used body protein stores to ensure a constant supply of N for fetal
      growth and milk production that minimized the effects of trophic mismatches on
      reproduction. The combination of migration and capital investment may therefore
      allow females to produce calves and attenuate the effects of both temporal and
      spatial mismatches between vegetation green-up and calf growth, which ultimately
      would reduce trophic feedbacks on population growth. Our data suggest that small
      changes in maternal allocation of proteins over the long period of gestation
      produce significant changes in calf mass as females respond to changes in
      resources that accompany changes in the size and distribution of the population.

PMID- 24015526
TI  - Strong contribution of immigration to local population regulation: evidence from
      a migratory passerine.
AB  - A mechanistic understanding of the dynamics of populations requires knowledge
      about the variation of the underlying demographic rates and about the reasons for
      their variability. In geographically open populations, immigration is often
      necessary to prevent declines, but little is known about whether immigration can
      contribute to its regulation. We studied the dynamics of a Red-backed Shrike
      population (Lanius collurio) over 36 years in Germany with a Bayesian integrated
      population model. We estimated mean and temporal variability of population sizes,
      productivity, apparent survival, and immigration. We assessed how strongly the
      demographic rates were correlated with population growth to understand the
      demographic reasons of population change and how strongly the demographic rates
      were correlated with population size to identify possible density-dependent
      mechanisms. The shrike population varied between 35 and 74 breeding pairs but did
      not show a significant trend in population size over time (growth rate 1.002 +/-
      0.001 [mean +/- SD]). Apparent survival of females (juveniles 0.06 +/- 0.01;
      adults 0.37 +/- 0.03) was lower than that of males (juveniles 0.10 +/- 0.01;
      adults 0.44 +/- 0.02). Immigration rates were substantial and higher in females
      (0.56 +/- 0.02) than in males (0.43 +/- 0.02), and average productivity was 2.76
      +/- 0.14. Without immigration, the Red-backed Shrike population would have
      declined strongly. Immigration was the strongest driver for the number of females
      while local recruitment was the most important driver for the number of males.
      Immigration of both sexes and productivity, but not local recruitment and
      survival, were subject to density dependence. Density-dependent productivity was
      not effectively regulating the local population but may have contributed to
      regulate shrike populations at larger spatial scales. These findings suggest that
      immigration is not only an important component to prevent a geographically open
      population from decline, but that it can also contribute to its regulation.

PMID- 24015527
TI  - Population-level scaling of avian migration speed with body size and migration
      distance for powered fliers.
AB  - Optimal migration theory suggests specific scaling relationships between body
      size and migration speed for individual birds based on the minimization of time,
      energy, and risk. Here we test if the quantitative predictions originating from
      this theory can be detected when migration decisions are integrated across
      individuals. We estimated population-level migration trajectories and daily
      migration speeds for the combined period 2007-2011 using the eBird data set. We
      considered 102 North American bird species that use flapping or powered flight
      during migration. Many species, especially in eastern North America, had looped
      migration trajectories that traced a clockwise path with an eastward shift during
      autumn migration. Population-level migration speeds decelerated rapidly going
      into the breeding season, and accelerated more slowly during the transition to
      autumn migration. In accordance with time minimization predictions, spring
      migration speeds were faster than autumn migration speeds. In agreement with
      optimality predictions, migration speeds of powered flyers scaled negatively with
      body mass similarly during spring and autumn migration. Powered fliers with
      longer migration journeys also had faster migration speeds, a relationship that
      was more pronounced during spring migration. Our findings indicate that powered
      fliers employed a migration strategy that, when examined at the population level,
      was in compliance with optimality predictions. These results suggest that the
      integration of migration decisions across individuals does result in population
      level patterns that agree with theoretical expectations developed at the
      individual level, indicating a role for optimal migration theory in describing
      the mechanisms underlying broadscale patterns of avian migration for species that
      use powered flight.

PMID- 24015528
TI  - The importance of progressive senescence in the biomass dynam of giant kelp
      (Macrocystis pyrifera).
AB  - Temporal variation in primary producer biomass has profound effects on the
      structure and function of the surrounding ecological community. The giant kelp
      (Macrocystis pyrifera) exhibits strong intra-annual variation in biomass density,
      which is better explained by the demographic rates of fronds than by those of
      whole plants. To better understand the processes controlling the dynamics of
      giant kelp fronds we collected monthly time-series data of frond initiation and
      survival. These data were used to determine how frond loss and frond initiation
      rates were predicted by factors thought to affect the growth and survival of
      Macrocystis, including external environmental factors (i.e., wave height, day
      length, temperature, nutrient concentration, and neighborhood density) and
      intrinsic biological characteristics (i.e., frond age, plant size, and
      nutritional status). Our results revealed that frond dynamics were better
      explained by intrinsic biological processes rather than external environmental
      factors. A metric of frond age structure that incorporated progressive senescence
      was the best predictor of frond loss rate, accounting for 58% of the explained
      variation in frond loss. A similar analysis revealed that frond age structure was
      also the single best predictor of frond initiation rate, accounting for 46% of
      the explained variation. To further examine the importance of senescence in
      biomass dynamics, we used frond age-dependent mortality and frond initiation
      rates to predict biomass in subsequent months and found that the model explained
      73% of the observed variation in biomass at our sites. Vegetation dynamics of
      many species including giant kelp are often considered largely in the context of
      external controls on resource availability and physical disturbance. Our results
      indicate that investigations of the processes controlling vegetation dynamics may
      benefit greatly from the inclusion of intrinsic biological factors such as age
      dependent mortality and growth, which can outweigh the effects of external
      forcing in accounting for fluctuations in vegetation biomass.

PMID- 24015529
TI  - Geographic coupling of juvenile and adult habitat shapes spatial population
      dynamics of a coral reef fish.
AB  - Marine spatial population dynamics are often addressed with a focus on larval
      dispersal, without taking into account movement behavior of individuals in later
      life stages. Processes occurring during demersal life stages may also drive
      spatial population dynamics if habitat quality is perceived differently by
      animals belonging to different life stages. In this study, we used a dual
      approach to understand how stage-structured habitat use and dispersal ability of
      adults shape the population of a marine fish species. Our study area and focal
      species provided us with the unique opportunity to study a closed island
      population. A spatial simulation model was used to estimate dispersal distances
      along a coral reef that surrounds the island, while contributions of different
      nursery bays were determined based on otolith stable isotope signatures of adult
      reef fish. The model showed that adult dispersal away from reef areas near
      nursery bays is limited. The results further show that different bays contributed
      unequally to the adult population on the coral reef, with productivity of
      juveniles in bay nursery habitat determining the degree of mixing among local
      populations on the reef and with one highly productive area contributing most to
      the island's reef fish population. The contribution of the coral reef as a
      nursery habitat was minimal, even though it had a much larger surface area. These
      findings indicate that the geographic distribution of nursery areas and their
      productivity are important drivers for the spatial distribution patterns of
      adults on coral reefs. We suggest that limited dispersal of adults on reefs can
      lead to a source-sink structure in the adult stage, where reefs close to
      nurseries replenish more isolated reef areas. Understanding these spatial
      population dynamics of the demersal phase of marine animals is of major
      importance for the design and placement of marine reserves, as nursery areas
      contribute differently to maintain adult populations.

PMID- 24015530
TI  - Unity through nonlinearity: a unimodal coral-nutrient interaction.
AB  - The magnitude and direction of biological effects of environmental disturbances
      can vary considerably, especially among studies that use presence/absence
      manipulations. Because nonlinearities (e.g., humped relationships) are common in
      biological systems, this heterogeneity in effects may arise if systems are
      similar in their responses but specific studies use few (e.g., two) levels, or a
      narrow range, of a factor. To test whether nonlinearity can explain heterogeneous
      responses to a common environmental disturbance, I examined the effect of
      nutrient enrichment on coral growth, which has been previously shown using simple
      (e.g., two-level) manipulations to yield positive, negative, or neutral
      responses. I subjected corals (Porites) to a nutrient gradient in situ for 28
      days. Coral growth rate increased (2.4-fold) then decreased (2.7-fold) with
      enrichment, returning to near-ambient values at the highest nutrient levels. This
      unimodal response could explain disparities among past findings and provides a
      compelling case for using regression designs to understand heterogeneity within
      ecological interactions.

PMID- 24015531
TI  - Functionally and phylogenetically diverse plant communities key to soil biota.
AB  - Recent studies assessing the role of biological diversity for ecosystem
      functioning indicate that the diversity of functional traits and the evolutionary
      history of species in a community, not the number of taxonomic units, ultimately
      drives the biodiversity--ecosystem-function relationship. Here, we simultaneously
      assessed the importance of plant functional trait and phylogenetic diversity as
      predictors of major trophic groups of soil biota (abundance and diversity), six
      years from the onset of a grassland biodiversity experiment. Plant functional and
      phylogenetic diversity were generally better predictors of soil biota than the
      traditionally used species or functional group richness. Functional diversity was
      a reliable predictor for most biota, with the exception of soil microorganisms,
      which were better predicted by phylogenetic diversity. These results provide
      empirical support for the idea that the diversity of plant functional traits and
      the diversity of evolutionary lineages in a community are important for
      maintaining higher abundances and diversity of soil communities.

PMID- 24015532
TI  - [Effects of sampling plot number on tree species distribution prediction under
      climate change].
AB  - Based on the neutral landscapes under different degrees of landscape
      fragmentation, this paper studied the effects of sampling plot number on the
      prediction of tree species distribution at landscape scale under climate change.
      The tree species distribution was predicted by the coupled modeling approach
      which linked an ecosystem process model with a forest landscape model, and three
      contingent scenarios and one reference scenario of sampling plot numbers were
      assumed. The differences between the three scenarios and the reference scenario
      under different degrees of landscape fragmentation were tested. The results
      indicated that the effects of sampling plot number on the prediction of tree
      species distribution depended on the tree species life history attributes. For
      the generalist species, the prediction of their distribution at landscape scale
      needed more plots. Except for the extreme specialist, landscape fragmentation
      degree also affected the effects of sampling plot number on the prediction. With
      the increase of simulation period, the effects of sampling plot number on the
      prediction of tree species distribution at landscape scale could be changed. For
      generalist species, more plots are needed for the long-term simulation.

PMID- 24015533
TI  - [Effects of road construction on regional vegetation types].
AB  - As a regional artificial disturbance component, road exerts great effects on
      vegetation types, and plays a substantial role in defining vegetation
      distribution to a certain extent. Aiming at the tropical rainforest degradation
      and artificial forest expansion in Yunnan Province of Southwest China, this paper
      analyzed the effects of road network extension on regional vegetation types. In
      the Province, different classes of roads had different effects on the vegetation
      types, but no obvious regularity was observed in the effects on the patch areas
      of different vegetation types due to the great variations of road length and
      affected distance. However, the vegetation patch number was more affected by
      lower class roads because of their wide distribution. As for different vegetation
      types, the vegetations on cultivated land were most affected by roads, followed
      by Castanopsis hystrix and Schima wallichii forests. Road network formation
      contributed most to the vegetation fragmentation, and there existed significant
      correlations between the human disturbance factors including village- and road
      distributions.

PMID- 24015534
TI  - [Scale-dependency of spatial variability of surface soil moisture under different
      land use types in Heihe Oasis, China].
AB  - To study the surface soil moisture spatial variability and its scale effect is of
      significance to understand the real variability of soil moisture and to
      objectively provide a reference for constructing a logical sampling scheme. By
      using "re-sampling" method, this paper studied the scale-dependency of the
      spatial variability of soil surface moisture in the woodland and farmland in the
      oasis ecological system in the middle reaches of Heihe River. The results showed
      that the variation degree of the surface soil moisture in the test woodland and
      farmland increased with increasing soil moisture content, and the coefficient of
      variation (CV) became closer to the true value when the sampling scale increased.
      Under both dry and moist conditions, and when the sampling amplitude increased
      within a definite range, the CV, Moran's I index, nugget, and sill of soil
      moisture in the woodland and farmland as well as the variation range in the
      woodland all increased, while the variation range in the farmland under arid
      condition did not show a stable regular pattern. When the sampling density
      increased within a definite range, the nugget and variation range increased, but
      the CV, Moran's I index, and sill showed less change.

PMID- 24015535
TI  - [Characteristics of evapotranspiration and crop coefficient of agroecosystems in
      semi-arid area of Loess Plateau, Northwest China].
AB  - Evapotranspiration (ET) is an important component of ground surface energy
      balance and water balance, and closely related to water cycle. By using eddy
      covariance technique, this paper studied the ET characteristics of agroecosystems
      in the semi-arid area of Loess Plateau in growth season (from April to
      September), 2010, and analyzed the relationships between crop coefficient and
      environmental factors. During the observation period, the diurnal variation of
      latent heat flux (LE) in each month was similar to single-peak curve, and the
      peak value (151.4 W x m(-2)) occurred in August. The daytime energy partitioning
      manner showed a significant seasonal variation, with LE/R(n) < H/R(n) (R(n) was
      net radiation, and H was sensible heat flux) from April to June, and LE/R(n) >
      H/R(n) from July to September. The daily ET rate also showed a significant
      seasonal variation, with the maximum of 4.69 mm x d(-1). The wind speed (W(s)),
      relative humidity (RH), soil water content (theta), and atmospheric vapor
      pressure deficit (D) were the major factors affecting the crop coefficient K(c)
      which was exponentially decreased with increasing W(s), exponentially increased
      with increasing RH and theta, and linearly decreased with increasing D.

PMID- 24015536
TI  - [Optimization of urban green space spatial arrangement based on supply-demand
      analysis: a case study in Nanjing City, China].
AB  - Urban green space has the functions of ecological and social services, and the
      two services levels are decided by the supply-demand relationship. However, the
      supply-demand of green space not only involves in quantity, but also refers to
      spatial distribution. Therefore, only greening indicators can not wholly reflect
      the true levels of green space services. Based on the supply-demand analysis and
      supported by the ArcGIS, this paper examined the ecological and social services
      levels of the urban green spaces in Nanjing City by using the evenness indicator
      and the rate the people could enjoy the public green space in their accessible
      area. Accordingly, the ecological and social services levels of the green space
      in the City were investigated. The results showed that in the east of Nanjing
      City, green spaces were rich, but high accessible ones were lack, which resulted
      in a moderate social service level. In the center of the City, green spaces were
      lack and distributed unevenly, resulting in the low levels of ecological and
      social services. In Hexi area, due to the shortage in ecological green space and
      its uneven distribution, the green spaces had a high level social service but a
      low level ecological service. In the southern and northern areas of the City,
      green spaces were in deficiency, uneven distribution, and lack in high
      accessible.

PMID- 24015537
TI  - [Landscape regionalization of agro-pastoral transitional zone using self
      organizing feature maps (SOFM) network: a case study of Inner Mongolia Autonomous
      Region, China].
AB  - Taking the agro-pastoral transitional zone of Inner Mongolia Autonomous Region,
      which has the most extrusive landscape differentiation in Northern China, as the
      object, a landscape spatial differentiation index was established based on the
      NDVI, integrated index of land use degree, and aridity index, and the
      characteristics of the landscape spatial differentiation were quantitatively
      identified by using SOFM network. The study area could be divided into six
      landscape zones, i. e., forest zone, forest-steppe transitional zone, agro-steppe
      mixed zone, typical steppe zone, steppe-desert transitional zone, and desert
      zone. As compared with the traditional schemes of physical geographical
      regionalization, our landscape regionalization could quickly regionalize the
      large scale landscape spatial differentiation in a quantitative way, and the
      regionalization results were basically in accordance with the original landscape
      characteristics and the landscape spatial differentiation pattern of the study
      area.

PMID- 24015538
TI  - [Land use change and its effects on ecosystem services value in Ji' nan City of
      Shandong Province, East China].
AB  - Based on the GIS software platform, referring to the China 'Terrestrial ecosystem
      services per unit area value', and by using transition matrix, Costanza
      evaluation formula, and sensitivity analysis, this paper studied the change
      characteristics of land use and ecosystem services value in Ji' nan City in 1989
      2009. During the study period, the built-up area in the City increased by 99.65
      km2, while agriculture land and green space reduced by 103.21 km2, 90.4% of which
      was taken by the built-up land. The total ecosystem services value decreased from
      256.22 x 10(6) yento 214.16 x 10(6) yen, with a decrement of 42.06 x 10(6) yen,
      mainly due to the decrease in the areas of agriculture land and green space. For
      the sustainable development of the population, resources, and environment in
      Ji'nan City, future urban planning should pay more attention on the natural
      resources protection, reasonable planning of land use structure, and maintenance
      of ecosystem stability and balance.

PMID- 24015539
TI  - [Assessment of ecosystem and its services conservation: indicators and methods].
AB  - To conserve ecosystem and its services is a frontier and hot topic in the
      researches of conservation ecology. This paper reviewed the newest concepts and
      methods in the assessment of ecosystem and its services conservation, with the
      focus on the indicators and criteria for assessing the conservation status and
      the endangerment level of ecosystem as well as the main methods of ecosystem
      services assessment and conservation (including benefit transfer, systematic
      modeling, and quantitative indicator-based estimation). With the consideration of
      the research progress and the demands of ecological conservation in China, some
      issues to be urgently solved were put forward: 1) formulating the indicators,
      criteria, and methods suitable for the assessment of ecosystem conservation in
      China, 2) developing the methodologies for the quantitative assessment of
      ecosystem services, 3) determining the demands and optimal spatial arrangement of
      ecosystem and its services conservation in China, and 4) establishing the
      policies and incentive mechanisms for ecosystem and its services conservation.
      The resolution of these issues would supply important guarantee to the
      development of ecological civilization in China.

PMID- 24015540
TI  - [Coupling coordination measurement of urbanization and eco-environment system in
      Huaihe River Basin of China based on fuzzy matter element theory].
AB  - Based on the statistical data of urbanization and eco-environment of 35 cities in
      the Huaihe River Basin of China in 2010, an index system of urbanization-eco
      environment system was established by using fuzzy matter element theory, and the
      weight of each indicator was calculated by entropy method. The improved function
      of the coupling coordination degree of urbanization and eco-environment was
      constructed to measure this coupling coordination degree in the Huaihe River
      Basin. In 2010, the development level of urbanization subsystem in the Basin was
      lower than that of the eco-environment subsystem, and the integrated coordination
      index of urbanization and eco-environment was 0.186, indicating that there was a
      gap between the two types of indicators. The average coupling degree of
      urbanization and eco-environment was 0.475, indicating that the urbanization-eco
      environment system was at antagonistic stage. There was a greater difference in
      the development level of urbanization subsystem, but a smaller difference in the
      development level of eco-environment subsystem among the cities. The average
      value of the coordination degree of all the cities was 0.706, indicating that the
      Huaihe River Basin was at high coordination coupling stage, and the integrated
      coherence and synergistic effect of urbanization and eco-environment construction
      in the Huaihe River Basin was higher.

PMID- 24015541
TI  - [Effects of reclaimed water recharge on groundwater quality: a review].
AB  - Reclaimed water recharge to groundwater is an effective way to relieve water
      resource crisis. However, reclaimed water contains some pollutants such as
      nitrate, heavy metals, and new type contaminants, and thus, there exists definite
      environmental risk in the reclaimed water recharge to groundwater. To promote the
      development of reclaimed water recharge to groundwater and the safe use of
      reclaimed water in China, this paper analyzed the relevant literatures and
      practical experiences around the world, and summarized the effects of different
      reclaimed water recharge modes on the groundwater quality. Surface recharge makes
      the salt and nitrate contents in groundwater increased but the risk of heavy
      metals pollution be smaller, whereas well recharge can induce the arsenic release
      from sedimentary aquifers, which needs to be paid more attention to. New type
      contaminants are the hotspots in current researches, and their real risks are
      unknown. Pathogens have less pollution risks on groundwater, but some virus with
      strong activity can have the risks. Some suggestions were put forward to reduce
      the risks associated with the reclaimed water recharge to groundwater in China.

PMID- 24015542
TI  - [Carbon storage of Pinus thunbergii and Robinia pseudoacacia plantations on
      Nanchangshan Island, Changdao County of Shandong Province, China].
AB  - Using indigenous tree species to transform large area pure plantations has been
      an effective close-to-nature forest management mode in China islands. By using
      the biomass allometric equation and combined with the investigation data from
      sampling plots, the carbon storage of the dominant species Pinus thunbergii and
      Robinia pseudoacacia in the plantations on the Nanchangshan Island of Miaodao
      Archipelago in Changdao County of Shandong Province was estimated. The average
      carbon storage in the arbor layer of P. thunbergii and R. pseudoacacia
      plantations was 56.81 and 37.26 t x hm(-2), respectively, being higher than the
      average carbon stock (27.62 t x hm(-2)) of tree plantations in Shandong Province.
      Slope aspect and stand density were the important environmental and biological
      factors affecting the tree's carbon stock in the Island, respectively. There was
      no significant correlation between the average cumulative rate of biomass in the
      arbor layer of P. thunbergi plantation and the stand age. The P. thunbergii with
      good carbon sequestration function could be an ideal tree species on Nanchangshan
      Island.

PMID- 24015543
TI  - [Seasonal dynamics and vertical distribution pattern of bud bank in different
      erosion environments on hilly-gully Loess Plateau of Northwest China].
AB  - This paper studied the vegetation composition, bud composition, and the seasonal
      dynamics and vertical distribution pattern of bud bank in five erosion
      environments (sunny gully slope, sunny hilly slope, hilltop, shady hilly slope,
      and shady gully slope) on the hilly-gully Loess Plateau of North Shaanxi. In the
      study area, the perennial species with perennial bud bank accounted for 80.3% of
      the total species, while the annual species with seasonal bud bank took up 19.7%
      of the total. In vegetation turning-green season, there was a relatively large
      perennial bud bank stock on the sunny hilly-gully slope where serious erosion
      occurred, while seasonal bud bank showed a higher bud bank density in blossom and
      fruit-setting season on the hilltop and two shady slopes where soil erosion
      intensity was relatively gentle. The proportion of underground bud bank to total
      perennial bud bank in different erosion environments was relatively stable. On
      the land surface, the perennial bud bank stock was larger on the sunny slope
      where the soil disturbance often occurred, whereas the seasonal bud bank stock
      was larger on the shady slope and hilltop. Due to the different species
      composition of plant communities in different erosion environments, in addition
      to the disturbance of soil erosion and the seasonal plant regeneration, the
      seasonal dynamics and vertical distribution pattern of bud bank changed. It was
      suggested that bud bank played an important role in the vegetation regeneration
      after the disturbance of soil erosion on the hilly-gully Loess Plateau of North
      Shaanxi.

PMID- 24015544
TI  - [Effects of elevated O3 concentration and UV-B radiation on the chlorophyll
      content and active oxygen metabolism of soybean leaves].
AB  - Taking the soybean (Glycine max) cultivar Tiefeng 29 as test material, and by
      using open-top chamber, this paper studied the effects of elevated O3
      concentration and UV-B radiation on the leaf chlorophyll content, lipid
      peroxidation, reactive oxygen species (ROS) production rate, anti-oxidation
      enzymes activities, and the grain yield. During the growth period of soybean, as
      compared with the control, the leaf Chl a, Chl b and Chl (a+b) contents under the
      stresses of O3 and UV-B had a decreasing trend, the relative electrical
      conductivity, malondialdehyde content, superoxide anion (O2) production rate, and
      hydrogen peroxide (H2O2) content increased, and the activities of superoxide
      dismutase, peroxidase and catalase as well as the grain yield decreased. O3+ UV
      stress aggravated the leaf membrane lipid peroxidation, promoted the ROS
      production, and decreased the plant antioxidant capacity and leaf chlorophyll
      content. The negative effects of O3 stress on soybean leaves were more close to
      the impacts of O3+UV stress, suggesting that O3 might play an important role in
      the combined stress.

PMID- 24015545
TI  - [Effects of soil PAHs pollution on plant ecophysiology].
AB  - Polycyclic aromatic hydrocarbons (PAHs) are the ubiquitous organic persistent
      pollutants in natural environments (especially in soil), giving serious potential
      risks to the eco-environment, plants, and human beings. At present, the
      remediation of PAHs-polluted soil is one of the hot topics in the research fields
      of soil and environment. Phytoremediation is one of the environmental restoration
      techniques with most potentiality. This paper reviewed the newest progress in the
      researches of the effects of soil PAHs pollution and its combined stress with
      other pollutants on the plant growth, morphological structure, photosynthesis,
      and antioxidant system, and prospected the important fields and hotspots of
      related researches in the future.

PMID- 24015546
TI  - [Effects of filamentous macroalgae on the methane emission from urban river: a
      review].
AB  - The global warming caused by greenhouse gases emission has raised serious
      concerns. Recent studies found that the carbon dioxide (CO2) and methane (CH4)
      emissions from river ecosystem can partly offset the carbon sequestration by
      terrestrial ecosystem, leading to a rethink of the effects of river ecosystem on
      the global carbon balance and greenhouse gases emission inventory. As an
      important primary producer in urban river ecosystem, filamentous macroalgae can
      deeply affect the carbon cycle process of river system through changing the
      abiotic and biotic factors in the interface of water-sediment. This paper
      reviewed the effects of filamentous macroalgae on the CH4 emission from urban
      river system from the aspects of 1) the effects of urbanization on the river
      ecosystem and its CH4 emission flux, 2) the effects of filamentous macroalgae on
      the CH4 generation and emission process in natural river systems, and 3) the
      effects of filamentous macroalgae on the primary productivity and CH4 emission
      process in urban river systems. The current problems and future directions in
      related researches were discussed and prospected.

PMID- 24015548
TI  - [Effects of different landscape patch structure on the diversity of arthropod
      community in tea plantations].
AB  - A field survey with random block design was conducted to study the effects of
      different landscape patch structure on the arthropod community in tea
      plantations. In the tea plantations with small woodland (QM) or Acacia confuse
      (XS) patches, predatory spider had the highest proportion, occupying 62.3% and
      69.5% of the total arthropods, respectively, being significantly higher than that
      in the tea plantations close to paddy field (DT) or near a village (RJ). The tea
      plantations with QM had the highest diversity index and species richness of
      arthropod community, while the evenness index and dominance index were not
      significantly different from the other tea plantations. The tea plantations with
      QM and XS had much richer natural enemies, and the order of the diversity index,
      evenness index, and richness index of natural enemies in the tea plantations
      ranked as QM > XS > DT > RJ. It was suggested that landscape patch structure had
      great effect on the diversity of arthropod community in tea plantations.

PMID- 24015547
TI  - [Effects of temperature and density on the mortality and reproduction of cotton
      aphid Aphis gossypii].
AB  - A laboratory cotton leaf disc experiment was conducted to study the effects of
      different temperature (32, 34, 36, 38, and 40 degrees C) and density (5, 25, 50,
      and 75 individuals per dish) on the mortality and reproduction of Aphis gossypii.
      With the increase of temperature, density, and culture duration, the cumulative
      mortality of A. gossypii presented an increasing trend. The parameters estimated
      by complementary log-log (CLL) model showed that the beta value decreased with
      the increase of density, indicating that the effects of temperature weakened with
      increasing density. The gamma value, a parameter for the time effect of
      temperature, changed with culture duration, indicating that the morality of A.
      gossypii was co-affected by the temperature and culture duration. The two-way
      ANOVA analysis of variance showed that temperature and density had significant
      effects on the fecundity of A. gossypii, and there existed interactive effect. At
      32-36 degrees C, the reproduction rate of A. gossypii decreased with the increase
      of density, but at 40 degrees C, no significant difference was observed in the
      reproduction rate under different densities, suggesting that the density effect
      was weakened with increasing temperature, i. e., the contribution of temperature
      and density to the survival and reproduction of individual varied with the ranges
      of the temperature and density. This study could provide reference for the
      monitoring and forecasting of A. gossypii population and for the improvement of
      pests control.

PMID- 24015549
TI  - [Effects of thinning intensity on Pinus tabulaeformis plantation in Huanglong
      Mountain, Northwest China: a comprehensive evaluation].
AB  - A sampling plot investigation was conducted on the seedling regeneration, stand
      growth, species diversity, and soil characteristics in a Pinus tabulaeformis
      plantation in Huanglong Mountain on the Loess Plateau of Northwest China after 7
      years of close-to-natural management thinning 15% (light thinning), 30% (medium
      thinning), and 45% (heavy thinning), with the effect of different thinning
      intensities evaluated. With the increase of thinning intensity, the amount and
      growth indices of 1-7 years old P. tabulaeformis seedlings increased, but the
      mean annual increments of the growth indices decreased after an initial increase,
      with the maximum under medium thinning. As compared with the control (un-thinned
      plantation), the individual volume under light, medium, and heavy thinning was
      increased by 20.9%, 32.1% and 52.6%, the volume per hm2 decreased by 4.4%, 15.1%,
      and 25.3%, and the mean annual growth rate of volume increased by 28.6%, 46.2%
      and 82.0%, respectively. The species diversity and soil characteristics were
      improved under thinning, with the order of heavy thinning > medium thinning >
      light thinning > un-thinning. In this study, 45% thinning was most suitable to
      the management of P. tabulaeformis plantation in Huanglong Mountain.

PMID- 24015550
TI  - [Health assessment of individual trees in natural Larix gmelinii forest in Great
      Xing' an Mountains of China].
AB  - To integrate the health assessment results of individual trees into the health
      assessment of subcompartment (or stand) scale could improve the accuracy of
      subcompartment (or stand) scale health assessment, and realize the coupling
      process between the individual tree scale and the subcompartment (or stand)
      scale, providing a theoretical basis for the realization of forest health
      management. Taking the natural Larix gmelinii forest in Great Xing' an Mountains
      as the object, a health assessment indicators system of individual trees was
      established, which included root state, canopy defoliation degree, crown
      transparency, crown overlap, crown dieback ratio, live crown ratio, crown
      skewness, and vertical competition index. The principal component analysis (PCA)
      was employed to eliminate the correlations, the entropy value method was adopted
      to confirm the weight of each indicator, and the health status of individual L.
      gmelinii was assessed by fuzzy synthetic evaluation (FSE) method. Based on the
      health assessment results, a prediction model of the individual tree health was
      established by discriminant analysis (DA) method. The results showed that the
      trees in sub-healthy gradation were up to 36.7%, and those in healthy gradation
      only reached 12.9%. The proportion of the trees in unhealthy gradation exceeded
      that of the trees in healthy gradation, occupying 21.1% of the total. The
      prediction accuracy of the established model was 86.3%. More rational and
      effective management measures should be taken to improve the tree health grade.

PMID- 24015551
TI  - [Distribution pattern of Rhododendron aganniphum var. schizopeplum population at
      the timberline of Sejila Mountains, Tibet of China].
AB  - Rhododendron aganniphum var. schizopeplum grows at the elevation of 4300-4500 m
      in Sejila Mountains, being a dominant species of shrub layer at the timberline of
      southeast Tibet. Based on the sampling plot investigation and basal diameter
      structure analysis, this paper studied the distribution pattern of R. aganniphum
      var. schizopeplum population at the timberline of Sejila Mountains. With the
      increase of altitude, the population density of R. aganniphum var. schizopeplum
      increased, but the population height decreased. At the same altitudes, the
      population density on the shady slope was larger than that on the sunny slope,
      while the basal diameter was smaller. On the two slope directions, the
      distribution of the basal diameter classes of the population appeared as "(see
      text for symbol)" shape, i. e., middle-aged individuals were more, while
      seedlings and saplings were relatively less. The intraspecific competition of R.
      aganniphum var. schizopeplum population was in the form of wave, being stronger
      on shady slope than on sunny slope, and existing self-thinning.

PMID- 24015552
TI  - [Effects of different forest restoration approaches on the soil quality in red
      soil region of Southern China].
AB  - In 2008-2009, an investigation was conducted on the effects of three typical
      forest restoration approaches, i. e., naturally restored secondary forest,
      artificially restored native species Pinus massoniana plantation (Masson pine
      plantation), and introduced species Pinus elliottii plantation (slash pine
      plantation), on the soil quality in red soil region of Southern China. The
      results showed that the soil moisture content, bulk density, particle
      composition, and the contents of total carbon (C), total nitrogen (N), total
      phosphorus (P), organic C, available N, available P, and available potassium (K)
      in natural secondary forest were all superior to those in artificial plantations.
      The soil physical, chemical, and microbial properties were integrated into a soil
      quality index, which was significantly higher (1.20 +/- 0.10) in natural
      secondary forest than in Masson pine plantation (0.59 +/- 0.03) and slash pine
      plantation (0.59 +/- 0.06). Our results suggested as compared with the
      restoration with native species P. massoniana and with introduced P. elliottii,
      natural restoration could be a better forest restoration approach to improve the
      soil quality in red soil region of Southern China.

PMID- 24015553
TI  - [Effects of exogenous Ca2+ on the seed germination of Koelreuteria paniculata in
      limestone area of Southwest China under drought stress].
AB  - In this paper, different arid environments in the limestone area of Southwest
      China were simulated by using different concentrations (0%, 5%, 15%, 25%, and
      30%) of PEG6000 (polyethylene glycol), and a gradient of exogenous Ca2+ (0, 15,
      20, 25, and 30 mmol x L(-1) of CaCl2) was installed to simulate the high calcium
      soil environments, aimed to study the effects of different concentration PEG6000,
      CaCl2, and their interactions on the seed germination characteristics of
      Koelreuteria bipinnata, one of the preferred species in the ecological
      restoration in limestone area. Under the action of CaCl2 alone, medium or low
      concentration exogenous Ca2+ had lesser effect on the seed germination
      parameters, but high concentration exogenous Ca2+ had inhibition effect on the
      seed germination. Medium or low concentration CaC12 could increase the seedling
      fresh biomass. When the PEG6000 concentration increased from 0% to 25%, the seed
      germination rate, germination potential, germination index, and vigor index
      showed a significant decreasing trend, and the seedling fresh biomass decreased
      remarkably. When certain concentration of exogenous Ca2+ was exerted to the
      drought treatment groups, medium or low concentration CaCl2 improved the seed
      germination characteristics, which compensated the loss from drought stress to a
      certain degree. When the CaCl2 concentration was up to 30 mmol x L(-1), the seeds
      were hard to germinate. Additionally, no seeds germinated under the condition of
      PEG with the concentration of 30%. It was suggested that applying definite
      concentration of exogenous Ca2+ could increase the seedling fresh biomass under
      PEG6000 stress, and make the seedlings more adapt to arid environment.

PMID- 24015554
TI  - [Uptake and accumulation characteristics of silicon and other nutritional
      elements in different age Phyllostachys praecox plants].
AB  - The samples of different age (1-4 years old) Phyllostachys praecox plants and
      their organs (leaf, branch, and culm) were collected from their main production
      area in Lin' an County, Zhejiang Province of East China to study the contents and
      the uptake and accumulation characteristics of silicon and other nutritional
      elements, as well as the interrelations between Si and other nutrient elements.
      In the P. praecox plants, the C content in aboveground part was in the order of
      culm > branch> leaf, whereas the Si, N, P, K, Ca, Mg, Al, Fe and Mn contents were
      in the order of leaf > branch > culm. Mn was mainly accumulated in leaf, while
      the other nine nutrient elements were mainly accumulated in the culm of 1-year
      old plants. The average Si content in the aboveground part of 3-4 year old plants
      was 13.66 g x kg(-1), suggesting that P. praecox belonged to Si accumulation
      plant. The leaf N, P, K, and Mg contents decreased, while the C, Al, and Mn
      contents increased with increasing plant age. The Si uptake by the aboveground
      part was mainly occurred in the second year (57.1%), while the N and K uptake was
      mainly in the first two years (67.7% - 93.7%). Thereafter, the N and K flowed out
      from the aboveground part, with the outflow rates reached 19.1% - 39.1% of the
      total accumulated amounts. The Si in P. praecox was significantly correlated with
      Ca, Al, and Mn, and negatively correlated with N, P, K, and Mg.

PMID- 24015555
TI  - [Effects of long-term rotation on the nutritional quality of wheat grain protein
      on dryland of Loess Plateau, Northwest China].
AB  - A long-term experiment was conducted on the dryland of Loess Plateau to study the
      effects of three typical rotation systems, including wheat-sainfoin rotation,
      wheat-pea rotation, and wheat-maize rotation, on the nutritional quality of wheat
      grain protein. Rotation system and the cropping years of rotated plants affected
      the nutritional quality of wheat grain protein in varying degrees. As compared
      with continuous wheat cropping, wheat-sainfoin rotation made the nutritional
      quality of wheat grain protein relatively stable, and the essential amino acid
      content, amino acid score, amino acid ratio coefficient, chemical score, and
      amino acid index of the protein all relatively high, being able to be adopted as
      a cropping system to product high quality protein wheat in Loess Plateau. Under
      wheat-pea rotation, the nutritional quality of wheat grain protein after 1-year
      pea cropping was relatively high, but the essential amino acid content of wheat
      grain protein after 2-year pea cropping was relatively low, and several essential
      amino acid scores and chemical score of the grain protein were lower than those
      under continuous wheat cropping. Furthermore, the essential amino acid index was
      12.2% lower than that under continuous wheat cropping. Therefore, wheat-pea
      rotation showed a relatively low nutritional quality of wheat grain protein.
      Under wheat-maize rotation, the nutritional quality of wheat grain protein was
      also relatively stable, but the crude protein and essential amino acid contents
      and amino acid balance level were lower than those under continuous wheat
      cropping.

PMID- 24015556
TI  - [Effects of supplemental irrigation based on the measurement of moisture content
      in different soil layers on the water consumption characteristics and grain yield
      of winter wheat].
AB  - In 2010-2011, a field experiment with high-yielding winter wheat cultivar Jimai
      22 was conducted to study the effects of supplemental irrigation based on the
      measurement of moisture content in different soil layers on the water consumption
      characteristics and grain yield of winter wheat. Four soil layers (0-20 cm, W1; 0
      40 cm, W2; 0-60 cm, W3; and 0-140 cm, W4) were designed to make the supplemental
      irrigation at wintering stage (target soil relative moisture content = 75%),
      jointing stage (target soil relative moisture content = 70%), and anthesis stage
      (target soil relative moisture content = 70%), taking no irrigation (W0) during
      the whole growth season as the control. At the wintering, jointing, and anthesis
      stages, the required irrigation amount followed the order of W3 > W2 > W1.
      Treatment W4 required smaller irrigation amount at wintering and jointing stages,
      but significantly higher one at anthesis stage than the other treatments. The
      proportion of the irrigation amount relative to the total water consumption over
      the entire growth season followed the sequence of W4, W3 > W2 > W1. By contrast,
      the proportion of soil water consumption relative to the total water consumption
      followed the trend of W1 > W2 > W3 > W4. With the increase of the test soil
      depths, the soil water utilization ratio decreased. The water consumption in 80
      140 cm and 160-200 cm soil layers was significantly higher in W2 than in W3 and
      W4. The required total irrigation amount was in the order of W3 > W4 > W2 > W1,
      the grain yield was in the order of W2, W3, W4 > W1 > W0, and the water use
      efficiency followed the order of W2, W4 > W0, W1 > W3. To consider the irrigation
      amount, grain yield, and water use efficiency comprehensively, treatment W2 under
      our experimental condition could be the optimal treatment, i. e., the required
      amount of supplemental irrigation based on the measurement of the moisture
      content in 0-40 cm soil layer should be feasible for the local winter wheat
      production.

PMID- 24015557
TI  - [Effects of watering and nitrogen fertilization on the growth, grain yield, and
      water- and nitrogen use efficiency of winter wheat].
AB  - A field experiment with split-plot design was conducted to study the effects of
      watering, nitrogen fertilization, and their interactions on the growth, grain
      yield, and water- and nitrogen use efficiency of winter wheat. Four watering
      levels (0, 900, 1200, and 1500 m3 x hm(-2)) in main plots and five nitrogen
      fertilization levels (0, 90, 150, 210, and 270 kg N x hm(-2)) in sub-plots were
      designed. The results showed that the grain yield, nitrogen absorption, nitrogen
      use efficiency, and nitrogen productive efficiency of winter wheat increased with
      increasing level of watering, but the nitrogen use efficiency and nitrogen
      productive efficiency decreased with increasing nitrogen fertilization level. The
      grain yield, nitrogen absorption, and nitrogen harvest index were increased with
      increasing nitrogen fertilization level when the nitrogen application rate was 0
      150 kg N x hm(-2), but not further increased significantly when the nitrogen
      application rate exceeded 150 kg x hm(-2). With the increasing level of watering,
      the water consumption amount (WCA) and the total water use efficiency increased,
      while the proportion of precipitation and soil water supply to WCA as well as the
      irrigation water use efficiency decreased. With the increasing level of nitrogen
      fertilization, the proportion of precipitation and watering amount to WCA
      increased, that of soil water supply to WCA decreased, and the total water use
      efficiency and irrigation water use efficiency decreased after an initial
      increase, with no significant differences among the treatments of 150, 210, and
      270 kg N x hm(-2). It was considered that under our experimental condition, 1500
      m3 x hm(-2) of watering amount plus 150 kg x hm(-2) of nitrogen fertilization
      could be the optimal combination for the high yielding and high efficiency.

PMID- 24015558
TI  - [Effects of different maize straw-returning modes on the soil respiration in a
      winter wheat field].
AB  - By using static chamber-TGC method, an in situ observation was conducted in a 10
      year conservation tillage winter wheat field to study the effects of different
      maize straw-returning modes on the soil respiration. The soil respiration had a
      significant positive correlation with the stubble height of maize straw, and two
      peaks were observed in wheat growth period. Under no tillage and no straw
      returning, the soil respiration was 72.5% of that under no tillage with all straw
      returning, and the soil respiration under conventional tillage and no straw-
      returning was 76.5% of that under conventional tillage with all straw-returning.
      The soil respiration was significantly positively correlated with the soil
      temperature and soil organic carbon at 20 cm depth, but no significant
      correlation with the soil organic carbon at 40 cm depth. A correlation was also
      observed between the soil respiration and soil moisture. The diurnal soil
      respiration in the treatments of all straw-returning presented a single-peak
      curve, with the peak at 18:00. There was a similar variation trend of soil
      temperature and soil respiration at the depth of 20 cm. Among the treatments of
      different straw-returning amounts, straw-returning with the stubble of 1 m height
      could reduce the soil respiration significantly, being a reasonable straw
      returning mode.

PMID- 24015559
TI  - [Changes of rice yield and quality in different accumulated temperature zones in
      Heilongjiang Province of Northeast China].
AB  - Field experiments were installed in different accumulated temperature zones in
      Heilongjiang Province to study the changes of the grain yield and quality of five
      major rice varieties with accumulated temperature. The rice yield changed with
      accumulated temperature in quadratic curve, and the correlation degree differed
      with the varieties. The panicle number and the grain number per panicle changed
      significantly in quadratic curve with accumulated temperature, while the 1000
      grain mass had less correlation with accumulated temperature. The sterile
      spikelet rate of grain increased obviously from suitable accumulated temperature
      zone to low accumulated temperature zone, but had no obvious change from suitable
      accumulated temperature zone to high accumulated temperature zone. The rates of
      chalky and head milled rice also changed with accumulated temperature in
      quadratic curve, i. e., there were both the lowest and the highest values in
      suitable accumulated temperature zone. The protein and amylose contents of the
      grain as well as the taste varied little with accumulated temperature. According
      to the sensitivity to temperature, the test rice varieties were divided into
      sensitive, medium, and blunt types, with the optimal and allowable cultivation
      accumulated temperature limits being 300 degrees C and 420 degrees C, 360 degrees
      C and 440 degrees C, and 380 degrees C and 520 degrees C, respectively. It would
      be very important to select the rice varieties with higher yield and better
      quality according to the local conditions, especially the accumulated
      temperature.

PMID- 24015560
TI  - [Short-term effects of different tillage modes combined with straw-returning on
      the soil labile organic carbon components in a farmland with rice-wheat double
      cropping].
AB  - A two-year (2009-2011) field experiment was conducted to study the effects of
      different tillage modes, straw-returning, and their interactions on the soil
      total organic carbon (TOC) and labile organic carbon (LOC) components (easily
      oxidizable organic carbon (EOC), water-soluble organic carbon (WSOC), and
      microbial biomass carbon (MBC)) at the soil depths of 0-7, 7-14, and 14-21 cm in
      a farmland with rice-wheat double cropping. In all treatments of straw-returning,
      the TOC and LOC contents in each soil layer were significantly higher than those
      without straw-returning. Under plowing tillage, the MBC content in 0-7 cm soil
      layer was significantly higher than that under rotary tillage, but the EOC
      content was in adverse. Rotary tillage made the TOC content in 7 - 14 cm soil
      layer being significantly higher, as compared with plowing tillage. The TOC,
      WSOC, and MBC contents in 14-21 cm soil layer under plowing tillage were
      significantly higher than those under rotary tillage. Plowing tillage combined
      with rice and wheat straws-returning made the soil TOC content being higher than
      the other treatments.

PMID- 24015561
TI  - [Effects of soil compaction stress on the growth and nitrogen metabolism of
      cucumber roots].
AB  - Taking cucumber cultivar 'Jinchun 4' as test material, a pot experiment was
      conducted to study the effects of soil compaction stress on cucumber root growth,
      respiration rate, activity, and nitrogen metabolism at different development
      stages. Two treatment were installed, i. e., bulk density 1.25 g x cm(-3) (loose
      soil, CK) and 1.55 g x cm(-3) (compacted soil). Under the stress of soil
      compaction, the total root length, root surface area, root forks, and root tips
      at different development stages decreased significantly, the root elongation
      growth and lateral root emergence were constrained remarkably, but the root
      radial growth was stimulated and the root average diameter was significantly
      increased. Meanwhile, both the root activity and the respiration rate decreased
      significantly, the root NO3(-), free amino acids, and soluble protein contents
      had a large decrease, the root nitrate reductase, glutamine synthetase, and
      glutamate synthase activities decreased significantly, whereas the root NH4(+)
      content had a significant increase. All the results indicated that under the
      stress of soil compaction, the uptake of nitrate by cucumber roots decreased, the
      nitrogen assimilation was inhibited, and the nitrogen metabolism was remarkably
      constrained.

PMID- 24015562
TI  - [Effects of exogenous spermidine on the nitrogen metabolism and main mineral
      elements contents of tomato seedlings under saline-alkali stress].
AB  - Taking two tomato cultivars Zhongza No. 9 and Jinpengchaoguan as test objects, a
      hydroponic experiment was conducted to study the effects of exogenous spermidine
      (Spd) on the tomato seedling nitrogen metabolism and main mineral elements
      contents under saline-alkali stress. Under the stress, the seedling dry biomass
      decreased significantly, and the plant growth was inhibited. The activities of
      nitrate reductase (NR), glutamine synthetase (GS), and glutamate synthase (GOGAT)
      and the contents of nitrate nitrogen (NO3(-)-N) and total N, K, Ca2+, and Mg2+ in
      leaves and roots decreased significantly, while the contents of ammonium nitrogen
      (NH4(+)-N), and Na+ had a significant increase. The activity of glutamate
      dehydrogenase (GDH) in the leaves of the two cultivars and in the roots of
      Zhongza No. 9 increased significantly, but that in the roots of Jinpengchaoguan
      had less change. The total P content in the leaves of the two cultivars decreased
      significantly, while that in the roots of Jinpengchaoguan and Zhongza No. 9 had a
      significant increase and less change, respectively. Applying exogenous Spd
      increased the assimilation of NH4+ by the plants through increasing the NR, GS
      and GOGAT activities, alleviated the nitrogen metabolic disturbance caused by the
      saline-alkali stress, and further, promoted the absorption, release, or
      transportation of P, K, Ca, Mg, and Na in different organs, maintained a proper
      balance among the nutrients, and improved the plant saline-alkali resistance.
      Zhongza No. 9 was more sensitive to the saline-alkali stress than
      Jinpengchaoguan, and the alleviation effect of exogenous Spd on the nitrogen
      metabolic disturbance and nutritional out-of-balance of Zhongza No. 9 was more
      obvious.

PMID- 24015563
TI  - [Alleviation effects of brassinolide on cucumber seedlings under NaCl stress].
AB  - This paper studied the effects of 2,4-epibrassinolide (EBR) on the photosynthesis
      and antioxidant system of cucumber seedling leaves under NaCl stress. As compared
      with the control, NaCl stress increased the leaf superoxide anion production
      rate, hydrogen peroxide content, malondialdehyde content, and cell membrane
      permeability while decreased the leaf net photosynthetic rate, stomatal
      conductance, transpiration rate, and intercellular CO2 concentration
      significantly, and inhibited the seedlings growth significantly. Applying EBR
      could increase the activities of leaf superoxide dismutase, peroxidase, and
      catalase, decrease the leaf superoxide anion production rate, hydrogen peroxide
      content, malondialdehyde content, and cell membrane permeability, make the leaves
      keep a higher photosynthetic rate, and thus, promote the seedlings growth, being
      able to effectively alleviate the damage of NaCl stress.

PMID- 24015564
TI  - [Variations of arsenic species in the solution of arsenic-contaminated paddy soil
      under flooding and at different temperatures].
AB  - Taking arsenic (As)-contaminated paddy soil as test object, and by using high
      performance liquid chromatography inductively coupled plasma-mass spectrometry
      (HPLC-ICP-MS), this paper studied the variations of As species in soil solution
      when the soil was sterilized or non-sterilized and incubated at different
      temperatures (5, 27, and 50 degrees C) under flooding. In the soil solution (pore
      water), only As(III) (arsenite), As(V) (arsenate), and DMA(V) ( dimethylarsinic
      acid) were detected, but no MMA(V)(mono methylarsinic acid) was found. With the
      increasing time of flooding and at the test temperatures, arsenite became the
      predominant species, averagely accounting for 64%, followed by As(V), with the
      proportion of 35%, and DMA(V), with the least proportion of 1%. Soil
      sterilization or non-sterilization had less effect on the concentrations of
      As(III) and DMA(V) in the soil solution, but remarkably affected the reduction of
      As(V) and the methylation of As(III). The promotion effect of soil sterilization
      decreased gradually with the increasing time of flooding and incubation. At 50
      degrees C and after flooded for 23 days, the DMA(V) concentration in sterilized
      soil solution was the highest and up to 23.7 ng x mL(-1), indicating that some
      thermophilic microbes remained in sterilized soil became predominant species, and
      promoted the methylation of As(III) In sum, the total arsenic concentration in
      non-sterilized soil at incubation temperature 27 degrees C and flooded for 23
      days was relatively low (501 ng x mL(-1)), and thus, in As-contaminated paddy
      rice planting areas, to adopt the water management mode of short cycle flooding
      non-flooding could decrease the As level in soil solution as far as possible, and
      in the same time, save water resources and ensure yielding.

PMID- 24015565
TI  - [Effects of mulberry/soybean intercropping on the plant growth and rhizosphere
      soil microbial number and enzyme activities].
AB  - A root separation experiment was conducted to investigate the plant growth and
      rhizosphere soil microbes and enzyme activities in a mulberry/soybean
      intercropping system. As compared with those in plastic barrier and nylon mesh
      barrier treatments, the plant height, leaf number, root length, root nodule
      number, and root/shoot ratio of mulberry and soybean in non-barrier treatment
      were significantly higher, and the soybean's effective nodule number was larger.
      The available phosphorous content in the rhizosphere soils of mulberry and
      soybean in no barrier and nylon mesh barrier treatments was increased by 10.3%
      and 11.1%, and 5.1% and 4.6%, respectively, as compared with that in plastic
      barrier treatment. The microbial number, microbial diversity, and enzyme
      activities in the rhizosphere soils of mulberry and soybean were higher in the
      treatments of no barrier and nylon mesh barrier than in the treatment of plastic
      barrier. All the results indicated that there was an obvious interspecific
      synergistic effect between mulberry and soybean in the mulberry/soybean
      intercropping system.

PMID- 24015566
TI  - [Effects of intercropping Sedum plumbizincicola and Apium graceolens on the soil
      chemical and microbiological properties under the contamination of zinc and
      cadmium from sewage sludge application].
AB  - Taking the vegetable soil with zinc- and cadmium contamination from a long-term
      sewage sludge application as the object, a pot experiment was conducted to study
      the remediation effect of Sedum plumbizincicola and Apium graceolens under
      continuous monoculture and intercropping. With the remediation time increased,
      both S. plumbizincicola and A. graceolens under monoculture grew poorly, but S.
      plumbizincicola under intercropping grew well. Under intercropping, the soil
      organic matter, total N, extractable N, and total P contents decreased
      significantly while the soil extractable K content had a significant increase,
      the counts of soil bacteria and fungi increased by 7.9 and 18.4 times and 3.7 and
      4.3 times, respectively, but the soil urease and catalase activities remained
      unchanged, as compared with those under A. graceolens and S. plumbizincicola
      monoculture. The BIOLOG ECO micro-plates also showed that the carbon sources
      utilization level and the functional diversity index of soil microbial
      communities were higher under intercropping than under monoculture, and the
      concentrations of soil zinc and cadmium under intercropping decreased by 5.8% and
      50.0%, respectively, with the decrements being significantly higher than those
      under monoculture. It was suggested that soil microbial effect could be one of
      the important factors affecting plant growth.

PMID- 24015567
TI  - [Effects of host plants on the life table parameters of experimental populations
      of Aphis gossypii].
AB  - A comparative study was conducted on the life table parameters of Aphis gossypii
      reared on five host plant species at (25 +/- 1) degrees C in laboratory. There
      existed significant differences in the durations of various developmental stages,
      adult longevity, mean offspring number per day, net reproductive rate, intrinsic
      rate of increase, finite rate of increase, mean generation time, and population
      doubling time for the A. gossypii populations reared on the host plants. For the
      aphids on Lagenaria siceraria var. turbinate, they needed the longest time (5.84
      days) to complete one generation, but for those on the other four plants, no
      significant differences were observed, with the time needed ranged from 5.24 to
      5.45 days. The adult longevity was the longest (20.04 days) on Cucumis sativus,
      but had no significant differences on the other four host plants, being from
      14.76 to 16.03 days. The populations' survival curves on all test host plants
      were of Deevey I, i. e., the death mainly occurred during late period. The
      survival rate on C. sativus was higher than those on the other four host plants.
      Based on the intrinsic rates of increase of A. gossypii, its host suitability was
      in the order of Cucumis melo var. saccharinus > Lagenaria siceraria var.
      turbinate > Cucurbita moschata var. melonaeformis > Cucumis sativus > Cucurbita
      pepo var. medullosa.

PMID- 24015568
TI  - [Effects of sediment on the early settlement stage of Sargassum horneri on rocky
      subtidal reefs].
AB  - By using sediment trap and suction pump to measure the relative sediment levels
      across different sites and water depths, and through the in situ measurements of
      Sargassum horneri density, this paper assessed the relationships between the
      distribution of S. horneri and the sediment levels and wave exposure on the rocky
      subtidal platforms around Gouqi Island, China. The laboratory-based experiments
      were also conducted to test the effects of different sediment levels on the
      attachment of S. horneri zygote and the survival rate of S. horneri germling
      after the attachment. S. horneri predominated at the sites with lesser sediment
      and wave exposure, but less distributed in the sites with high level sediment and
      wave-exposure. At different water depths, the distribution of S. horneri was
      negatively correlated with the amount of sediment. A medium dusting (dry mass
      10.47 mg x cm(-2), approximate 0.543 mm deep) of sediment on the plate reduced
      the percentage of S. horneri zygotes attached to the substratum by 4.4%, and a
      heavy dusting (dry mass 13.96 mg x cm(-2), approximate 0.724 mm deep) of sediment
      on the plate completely prevented the attachment. One week after the settlement
      of the zygotes, there were 24% of the germlings still survived when the dry mass
      sediment coverage was 13.96 mg x cm(-2). However, when the dry mass sediment
      coverage was up to 34.9 mg x cm(-2) (approximate 1.81 mm deep), 100% of the
      germlings died. Overall, the distribution of S. horneri was not only related to
      sediment level, but also restricted by wave exposure to some extent. Sediment
      level was a critical factor affecting the distribution of S. horneri,
      particularly at its zygote attachment stage.

PMID- 24015569
TI  - [Feeding ecology of Amblychaeturichthys hexanema in Jiaozhou Bay, China].
AB  - From February to November 2011, four seasonal bottom trawl surveys were conducted
      in the Jiaozhou Bay of China. A total of 624 Amblychaeturichthys hexanema
      individuals were collected to analyze their stomach contents, with the feeding
      ecology of A. hexanema studied. The prey items of A. hexanema included more than
      40 species, among which, Alpheus japonicas, Philine kinglippini, and Leptochela
      gracilis were the dominant prey species. The diet composition of A. hexanema had
      an obvious seasonal variation, with the gastropods, fish, decapods, and
      microcrustacean being the most important prey items in spring, summer, autumn,
      and winter, respectively. This phenomenon could be mainly related to the seasonal
      variations in the species and biomass of the preys in Jiaozhou Bay. With the
      increase of predator size, the prey species of A. hexanema varied from small size
      copepod to larger sizes P. kinglippini, Raphidopus ciliates, and A. japonicas.
      The canonical correspondence analysis (CCA) showed that water temperature and
      salinity were the most important factors affecting the feeding of A. hexanema,
      followed by predator size and water pH.

PMID- 24015570
TI  - [Effects of temperature on the embryonic development and larval growth of Sepia
      lycidas].
AB  - A single-factor experiment was conducted to study the effects of different
      temperature (15, 18, 21, 24, 27, 30, and 33 degrees C) on the embryonic
      development and larval growth of Sepia lycidas, aimed to search for the optimum
      temperature for the development and growth of S. lycidas. The results showed that
      temperature had significant effects on the embryonic development and larval
      growth of S. lycidas (P < 0.05). The suitable temperature for hatching ranged
      from 21 degrees C to 30 degrees C, and the optimum temperature was 24 degrees C.
      At the optimum temperature, the hatching rate was (93.3 +/- 2.9)%, incubation
      period was (24.33 +/- 0.58) d, hatching period was (6.00 +/- 1.00) d, completely
      absorked rate of yolk sac was (96.4 +/- 3.1)%, and newly hatched larvae mass was
      (0.258 +/- 0.007) g. The effective accumulated temperature model was N =
      284.42/(T-12.57). The suitable temperature for the larval survival and growth
      ranged from 21 degrees C to 30 degrees C, and the optimum temperature was from 24
      degrees C to 27 degrees C. At the optimum temperature, the survival rate ranged
      from 70.0% to 73.3%, and the specific growth rate was from 2.4% to 3.8%.

PMID- 24015571
TI  - [Species composition and geographical distribution of threatened fishes in Yunnan
      Province of Southwest China].
AB  - Based on the related published papers, and by using Geographic Information System
      (ArcGIS 9.3), this paper analyzed the species composition and geographical
      distribution of threatened fishes in Yunnan Province of Southwest China. There
      were 83 threatened species living in the Province, belonging to 5 orders, 13
      families, and 47 genera. Cypriniformes was absolutely dominant, with 64 species,
      followed by Siluriformes, with 16 species. Cyprinidae fishes had 51 species,
      accounting for 79.7% of Cypriniformes. The most species of Cyprinid fishes were
      of Barbinae (14 species), Cyprininae (10 species), and Cultrinae (10 species).
      The threatened fishes could be divided into two zoogeographical regions, i. e.,
      Tibetan Plateau region and Oriental region, and their species composition and
      geographical distribution were resulted from the historical evolution adapted to
      the related environments. Whatever in rivers and in lakes, the Cyprinid fishes
      were both absolutely dominant, occupying 36.1% and 31.3% of the total,
      respectively. The Cyprinid fishes in rivers were mostly of endangered species,
      while those in lakes were mostly of vulnerable species. The factors affecting the
      threatened fishes in the Province were discussed from the two aspects of
      geodynamic evolution and present situation.

PMID- 24015572
TI  - [Ecological security of wastewater treatment processes: a review].
AB  - Though the regular indicators of wastewater after treatment can meet the
      discharge requirements and reuse standards, it doesn't mean the effluent is
      harmless. From the sustainable point of view, to ensure the ecological and human
      security, comprehensive toxicity should be considered when discharge standards
      are set up. In order to improve the ecological security of wastewater treatment
      processes, toxicity reduction should be considered when selecting and optimizing
      the treatment processes. This paper reviewed the researches on the ecological
      security of wastewater treatment processes, with the focus on the purposes of
      various treatment processes, including the processes for special wastewater
      treatment, wastewater reuse, and for the safety of receiving waters. Conventional
      biological treatment combined with advanced oxidation technologies can enhance
      the toxicity reduction on the base of pollutants removal, which is worthy of
      further study. For the process aimed at wastewater reuse, the integration of
      different process units can complement the advantages of both conventional
      pollutants removal and toxicity reduction. For the process aimed at ecological
      security of receiving waters, the emphasis should be put on the toxicity
      reduction optimization of process parameters and process unit selection. Some
      suggestions for the problems in the current research and future research
      directions were put forward.

PMID- 24015573
TI  - Anchored metal nanoparticles: effects of support and size on their energy,
      sintering resistance and reactivity.
AB  - Many catalysts consist of metal nanoparticles anchored to the surfaces of oxide
      supports. These are key elements in technologies for the clean production and use
      of fuels and chemicals. We show here that the chemical reactivity of the surface
      metal atoms on these nanoparticles is closely related to their chemical
      potential: the higher their chemical potential, the more strongly they bond to
      small adsorbates. Controlling their chemical potential by tuning the structural
      details of the material can thus be used to tune their reactivity. As their
      chemical potential increases, this also makes the metal surface less noble,
      effectively pushing its behavior upwards and to the left in the periodic table.
      Also, when the metal atoms are in a nanoparticle with higher chemical potential,
      they experience a larger thermodynamic driving force to sinter. Calorimetric
      measurements of metal vapor adsorption energies onto clean oxide surfaces in
      ultrahigh vacuum show that the chemical potential increases with decreasing
      particle size below 6 nm, and, for a given size, decreases with the adhesion
      energy between the metal and its support, Eadh. The structural factors that
      control the metal/oxide adhesion energy are thus also keys for tuning catalytic
      performance. For a given oxide, Eadh increases with (deltaHsub,M-
      deltaHf,MOx)/OmegaM2/3 for the metal, where deltaHsub,M is its heat of
      sublimation, deltaHf,MOx is the standard heat of formation of that metal's most
      stable oxide (per mole of metal), and OmegaM is the atomic volume of the bulk
      solid metal. The value deltaHsub,M--deltaHf,MOx equals the heat of formation of
      that metal's oxide from a gaseous metal atom plus O2(g), so it reflects the
      strength of the chemical bonds which that metal atom can make to oxygen, and
      OmegaM2/3 simply normalizes this energy to the area per metal atom, since Eadh is
      the adhesion energy per unit area. For a given metal, Eadh to different clean
      oxide surfaces increases as: MgO(100) approximately TiO2(110) < or = alpha
      Al2O3(0001) < CeO2-x(111) < or = Fe3O4(111). Oxygen vacancies also increase Eadh,
      but surface hydroxyl groups appear to decrease Eadh, even though they increase
      the initial heat of metal adsorption.

PMID- 24015574
TI  - Exploring surface science and restructuring in reactive atmospheres of
      colloidally prepared bimetallic CuNi and CuCo nanoparticles on SiO2 in situ using
      ambient pressure X-ray photoelectron spectroscopy.
AB  - Bimetallic nanoparticles (to approximately 11 nm diameter) of CuNi and CuCo were
      prepared by a new synthetic route and the 1:1 atomic ratio of their constituent
      elements confirmed using STEM-EDS at a single particle level. These
      nanoparticles, supported on the native oxide layer of a silicon wafer, were
      studied in situ in a series of reactive gas atmospheres (H2 --> CO or CO/H2 -->
      O2 --> H2) using ambient pressure X-ray photoelectron spectroscopy (AP-XPS).
      Despite the deliberate similarity of nickel and cobalt with respect to copper,
      their restructuring behaviour is different. CuNi nanoparticles were found to
      surface segregate nickel in H2, but copper in O2 reversibly, while CuCo
      nanoparticles were found to surface segregate copper irreversibly when exposed to
      O2, such that the surface remains copper rich when re-exposed to H2. Both systems
      also restructure in opposition to the behaviour predicted by the surface free
      energies and enthalpies of oxide formation of the elements from which they are
      comprised--factors that are seen to control restructuring and surface segregation
      in many similar systems.

PMID- 24015575
TI  - The structure of AuPd nanoalloys anchored on spherical polyelectrolyte brushes
      determined by X-ray absorption spectroscopy.
AB  - Well-defined and facetted bimetallic gold-palladium nanoalloys have been
      synthesized and anchored in spherical polyelectrolyte brushes (SPB) as composite
      particles (AuPd@SPB). These particles are better catalysts in aqueous phase than
      the pure metals. The atomistic arrangement of these nanoalloys has been analysed
      by extended X-ray absorption fine structure (EXAFS) spectroscopy at the Au-L3 and
      the Pd-K absorption edge. The samples with high amounts of gold appear as almost
      statistically mixed random alloys. Alloy compositions with less gold show slight
      enrichment of Pd at the surface of the particle. In addition, signals of non
      metallic palladium appear at the Pd-K edge which indicate the presence of the
      Pd2+ species in addition to metallic palladium. The relation of these structural
      features to the catalytic activity is discussed.

PMID- 24015576
TI  - Semi-hydrogenation of alkynes at single crystal, nanoparticle and biogenic
      nanoparticle surfaces: the role of defects in Lindlar-type catalysts and the
      origin of their selectivity.
AB  - For the first time, the method of shell-isolated nanoparticle Raman spectroscopy
      (SHINERS) is used in combination with cyclic voltammetry (CV) and reactivity
      studies to investigate the adsorption behaviour of a series of three alkynes
      undergoing hydrogenation on nanoparticle, single crystal and bacteria/graphite
      supported platinum surfaces. It is found that a strong association of alkynes
      with defect sites to produce a long-lived di-sigma/pi-alkene surface complex
      allows for deep hydrogenation of this intermediate to the alkane product. In
      contrast, when platinum surface defect sites are blocked by either bismuth or
      polyvinylpyrrolidone (PVP) (and thus leaving behind only Pt{111} terrace
      adsorption sites), large increases in selectivity to the semi-hydrogenation
      product are observed for all three alkynes. This finding is consistent with
      SHINERS collected from both well-ordered and roughened Pt{111} electrodes which
      revealed that the di-sigma/pi-bonded surface intermediate is hardly formed at all
      on Pt{111} unless defect sites are introduced via electrochemical roughening. As
      a general method of producing selective catalysts, the elimination of toxic heavy
      metals from Lindlar-type catalyst, used commonly in organic chemistry, and their
      replacement by more benign, organic species adsorbed at defect sites is
      discussed.

PMID- 24015577
TI  - Pt-group bimetallic nanocrystals with high-index facets as high performance
      electrocatalysts.
AB  - Bimetallic nanocrystals bound by high-index facets are promising catalysts, as
      they have both electronic effects from alloying and surface structure effects
      from high-index facets. Herein, we mainly focused on electrochemical preparation
      of two new Pt-Rh nanocrystals with high-index facets: {830}-bound tetrahexahedron
      and {311}-bound trapezohedron, and their excellent electrocatalytic properties
      for ethanol oxidation, especially the ability to break C-C bonds. Combining
      previous results about surface-modified tetrahexahedral Pt nanocrystals, we
      discuss the correlation of alloy and surface effects of the bimetallic system.

PMID- 24015578
TI  - Shape-selected bimetallic nanoparticle electrocatalysts: evolution of their
      atomic-scale structure, chemical composition, and electrochemical reactivity
      under various chemical environments.

PMID- 24015579
TI  - Helium droplets: a new route to nanoparticles.
AB  - Helium droplets are large helium clusters that are capable of picking up
      individual atoms and molecules and show promise as nano-reactors for the
      synthesis of unique nanoparticles. In particular, the sequential addition of
      materials of different types offers opportunities for the fabrication of novel
      core-shell nanoparticles that cannot be synthesised by other methods. To exploit
      this potential, here we have carried out a mass spectrometry investigation on
      metal clusters in order to establish how to control the doping conditions for the
      fabrication of nanoparticles in superfluid helium droplets, and in particular to
      develop a recipe to control core and shell ratios in the case of core-shell
      nanoparticles. Several types of metal nanoparticles, including pure Ag, Au and Ni
      nanoparticles, and Ag/Au and Ni/Au core-shell systems, have been synthesised and
      then removed from the helium droplets by deposition on substrates for ex situ
      investigations using high-resolution transmission electron microscopy (TEM) and X
      ray photoelectron spectroscopy (XPS). The TEM imaging has been used to estimate
      the sizes of nanoparticles, which show a bimodel distribution under the
      conditions employed. We also present the first evidence that crystalline metal
      nanoparticles are formed by self-assembly of metal atoms in helium droplets. The
      XPS investigation of Ni/Au core-shell nanoparticles shows an absence of any Au 4f
      core-level shift that would occur on alloying of Au and Ni, which provides the
      first direct evidence for the successful formation of core-shell nanoparticles
      using superfluid helium droplets.

PMID- 24015580
TI  - General discussion.

PMID- 24015581
TI  - Charge competition with oxygen molecules determines the growth of gold particles
      on doped CaO films.
AB  - The influence of gas-phase oxygen on the growth of Au nanoparticles on Mo-doped
      CaO films has been investigated by means of low temperature scanning tunnelling
      microscopy and X-ray photoelectron spectroscopy. Whereas at ideal vacuum
      conditions, only 2D Au islands develop on the oxide surface, the fraction of 3D
      deposits increases with increasing O2 pressure until they become the dominant
      species in 106 mbar oxygen. The morphology crossover arises from changes in the
      interfacial electron flow between Mo donors in the CaO lattice and different ad
      species on the oxide surface. In the absence of 02 molecules, the donor electrons
      are predominately transferred to the Au ad-atoms, which consequently experience
      enhanced binding to the oxide surface and agglomerate into 2D islands. In an
      oxygen atmosphere, on the other hand, a substantial fraction of the excess
      electrons is trapped by adsorbed O2 molecules, while the Au atoms remain neutral
      and assemble into tall 3D particles that are typical for non-doped oxides. Our
      experiments demonstrate how the competition for charge between different
      adsorbates governs the physical and chemical properties of doped oxides, so
      widely used in heterogeneous catalysis.

PMID- 24015582
TI  - Preparation and structure of a single Au atom on the TiO2(110) surface: control
      of the Au-metal oxide surface interaction.
AB  - Three-dimensional Au structures on bare and organic-compound-modified TiO2(110)
      surfaces were interrogated by Au L3-edge polarization dependent total reflection
      fluorescence X-ray absorption fine structure (PTRF-XAFS) spectroscopy. On the
      bare TiO2(110) surface, icosahedral Au55 nanoclusters were the main product
      found. When the surfaces were modified with ortho or meso mercaptobenzoic acid (o
      MBA or m-MBA), Au was atomically dispersed. Sulfur atoms in the o- and m- MBA
      formed strong covalent bonds with Au to produce stable Au-MBA (o- and m- forms)
      surface complexes. On the other hand, only oxygen atoms on the surface did not
      make a strong enough interaction to stabilize the Au species. We discuss how the
      Au species formed on the modified TiO2(110) surface and the possibility to
      control the Au structure by the surface modification method.

PMID- 24015583
TI  - Operando atomic structure and active sites of TiO2(110)-supported gold
      nanoparticles during carbon monoxide oxidation.
AB  - It is well known that gold nanoparticles supported on TiO2 act as a catalyst for
      CO oxidation, even below room temperature. Despite extensive studies, the origin
      of this catalytic activity remains under debate. Indeed, when the particle size
      decreases, many changes may occur; thus modifying the nanoparticles' electronic
      properties and consequently their catalytic performances. Thanks to a state-of
      the-art home-developed setup, model catalysts can be prepared in ultra-high
      vacuum and their morphology then studied in operando conditions by Grazing
      Incidence Small Angle X-ray Scattering, as well as their atomic structure by
      Grazing Incidence X-ray Diffraction as a function of their catalytic activity. We
      previously reported on the existence of a catalytic activity maximum observed for
      three-dimensional gold nanoparticles with a diameter of 2-3 nm and a height of 6
      7 atomic planes. In the present work we correlate this size dependence of the
      catalytic activity to the nanoparticles' atomic structure. We show that even when
      their size decreases below the optimum diameter, the gold nanoparticles keep the
      face-centered cubic structure characteristic of bulk gold. Nevertheless, for
      these smallest nanoparticles, the lattice parameter presents anisotropic strains
      with a larger contraction in the direction perpendicular to the surface. Moreover
      a careful analysis of the atomic-scale morphology around the catalytic activity
      maximum tends to evidence the role of sites with a specific geometry at the
      interface between the nanoparticles and the substrate. This argues for models
      where atoms at the interface periphery act as catalytically active sites for
      carbon monoxide oxidation.

PMID- 24015584
TI  - CO and O overlayers on Pd nanocrystals supported on TiO2(110).
AB  - We have prepared a model catalytic system by depositing Pd onto a TiO2(110)
      surface held at approximately 720 K. Scanning tunneling microscopy (STM) reveals
      well-defined Pd nanocrystals consisting of (111) top facets with {111} and {100}
      side facets. The Pd nanocrystals go down to about 10 nm in width and 1.3 nm in
      height. Top facets can be imaged with atomic resolution, indicating the absence
      of TiOx encapsulation. The model catalyst was probed by exposure to CO and O2. By
      varying the CO exposure, different CO overlayers were formed on the (111) top
      facets, with coverages ranging from 0.33 to 0.75 of a monolayer. Near edge X-ray
      absorption fine structure (NEXAFS) measurements at 300 K reveal that at around
      0.5 ML coverage, CO is oriented with the molecular axis more or less normal to
      TiO2(110). Dosing small amounts of 02 separately on a Pd/ TiO2(110) surface led
      to an overlayer of p(2 x 2)-O formed on the (111) top facet of the Pd
      nanocrystals at 190 K.

PMID- 24015585
TI  - Fabrication of complex model oxide catalysts: Mo oxide supported on Fe3o4(111).
AB  - Industrial catalysts for the oxidation of methanol to formaldehyde consist of
      iron molybdate [Fe2(MoO4)3]. Using a variety of techniques we have previously
      shown that the surface of these catalysts is segregated in MoO3, and in order to
      understand the relationship between surface structure and reactivity for these
      systems we have begun a surface science study of this system using model, single
      crystal oxides. Model catalysts of molybdenum oxide nanoparticles and films on an
      Fe3O4(111) single crystal were fabricated by the hot-filament metal oxide
      deposition technique (HFMOD), where molybdenum oxides were produced using a
      molybdenum filament heated in an oxygen atmosphere. Low energy electron
      diffraction (LEED), X-ray photoelectron spectroscopy (XPS), and scanning
      tunnelling microscopy (STM) have been used to investigate molybdenum oxide
      nanoparticles and films deposited on Fe3O4(111). The molybdenum oxide film forms
      in the highest oxidation state, +6, and is remarkably stable to thermal
      treatment, remaining on the surface to at least 973 K. However, above
      approximately 573 K cation mixing begins to occur, forming an iron molybdate
      structure, but the process is strongly Mo coverage dependent.

PMID- 24015586
TI  - Stability and migration barriers of small vanadium oxide clusters on the
      CeO2(111) surface studied by density functional theory.
AB  - By virtue of periodic density functional theory, we investigate structure and
      thermodynamic stability of (VO)k and (VO2)k (k = 1, 2, 3) clusters deposited on
      the CeO2(111) surface, which serve as models for the very active sub-monolayer
      vanadia catalyst on a ceria support. We find V always completely oxidized
      (oxidation state +5) and coordinated to four O atoms. As a consequence, Ce4+ is
      (partially) reduced to Ce3+. Thus, localized Ce-4f states are populated, which
      requires an onsite U-term (PBE+U) to avoid over-delocalization off-electrons.
      Importantly, trimers of VO2 were found to be extraordinarily stable
      (agglomeration energy: -1.68 eV), whereas aggregation of VO species on CeO2(111)
      is thermodynamically clearly unfavourable (agglomeration energy: 3.45 eV). As a
      consequence a large area of the VnOm phase diagram (for relevant temperatures) is
      dominated by the VO2 trimer. The latter is less active towards
      reduction/oxidation than the active monomer and dimer of VO2, which are not
      present in the phase diagram at all, although directly observed by recent STM
      measurements. This suggests that kinetic effects hinder VO2 to grow into larger
      oligomers. The lowest migration energy barrier we found is as high as 1.95 eV,
      which indicates that adsorbed monomeric VO2 is "kinetically locked" at low
      temperatures and explains why monomers are stabilized on the ceria surface.

PMID- 24015587
TI  - Mechanistic insights into the partial oxidation of acetic acid by O2 at the dual
      perimeter sites of a Au/TiO2 catalyst.
AB  - The unique interfacial sites of Au nanoparticles supported on TiO2 are known to
      catalyze the activation of oxygen and it's addition to small molecules including
      H2, CO, NO and propylene. Herein we extend these ideas and show that the unique
      Au-Ti dual perimeter sites that form at the Au/TiO2 interface can also catalyze
      more demanding C-H and C-O bond activation reactions involved in the
      deoxygenation organic acids such as acetic acid. We have shown previously that
      acetic acid can be partially oxidized on a Au/TiO2 catalyst to form a novel gold
      ketenylidene (Au2==C==C==O) intermediate. In the present work we use in situ
      infrared spectroscopy and first-principle density functional theory (DFT) to
      examine the mechanism and the kinetics by which this reaction proceeds. The
      reaction was found to be localized at the dual perimeter sites of the Au/TiO2
      catalyst, where 02 was activated. In contrast to Au/TiO2, no ketenylidene
      formation was observed on a similar Au/SiO2 catalyst or a TiO2 blank sample. The
      reaction involves the activation of multiple C-H bonds as well as the C-O bond in
      the adsorbed CH3COO species. C-O bond scission is postulated to occur at the TiO2
      sites, while C-H bond scission occurs on Au sites, both near the active Au-Ti4+
      dual perimeter sites. 18O2 isotopic labeling indicated that the O moiety of the
      ketenylidene species originates from the acetic acid during the oxidation process
      involving molecular O2. The rate-limiting step was found to be the C--O bond
      scission resulting in an apparent overall activation energy of 1.72 eV as
      determined from DFT calculations. This is in very good agreement with the
      experimentally measured apparent activation energy of 1.7 +/- 0.2 eV. A deuterium
      kinetic isotope effect of approximately 4 indicates that C-H bond activation is
      kinetically involved in the overall acetate oxidation reaction.

PMID- 24015588
TI  - Catalyst nano-particle size dependence of the Fischer-Tropsch reaction.
AB  - Computational catalytic studies indicate that the elementary reactions that
      constitute the Fischer-Tropsch reaction strongly dependent on the structure of
      the catalyst reaction center. Recent experimental evidence is available that, for
      metallic Fischer-Tropsch catalysts such as Co or Ru, the very small metallic
      particles show altered catalytic performance. To distinguish between changes in
      the relative concentration of reaction centres, changes in chemical reactivity,
      or rate controlling steps, transient SSITKA data are extremely useful. Here, we
      present kinetics simulations to extract molecular kinetic information from SSITKA
      data. We have applied such simulations to interpret published experimental SSITKA
      data on nano-particle size dependent Fischer-Tropsch (FT) kinetics. The FT
      catalytic cycle consists of four essential reaction steps. Their relative size
      determines activity as well as selectivity. The simulated SSITKA indicate three
      different regimes with different kinetic behaviour, where the two fundamental
      regimes to distinguish are the monomer-formation-limited and the chain-growth
      limited regime. Particle size changes shift kinetics from one to the other
      regime. We note different effects of supports and choice of metal composition on
      changes in elementary rates or the relative number of reactive centres when the
      particle size is decreased in the nanometre regime.

PMID- 24015589
TI  - A computational study of the influence of the ceria surface termination on the
      mechanism of CO oxidation of isolated Rh atoms.
AB  - The reaction mechanism for CO oxidation by isolated Rh atoms stabilized on
      CeO2(111), CeO2(110) and CeO2(100) surfaces is investigated by a combination of
      Density Functional Theory and kinetic Monte Carlo calculations. On Rh/ CeO2(111),
      one adsorbed CO molecule on Rh was found to form a stable intermediate structure
      with surface O. The reaction cycle cannot be closed because of the strong
      adsorption of the CO2 complex. The presence of a second adsorbed CO significantly
      decreases the desorption energy, thus opening a possible reaction path. Formation
      of the oxygen vacancy is accompanied by reduction of surface cerium. On
      Rh/CeO2(110), adsorbed CO can easily react with a ceria surface O atom due to the
      lower Ce-O bond energy. Since surface O atom migration is much more facile on
      Rh/CeO2(110) than on Rh/CeO2(111), CO2 desorption is also more easy for the
      former surface. Molecular oxygen will adsorb on the resulting vacancy. After
      desorption of the second CO2 product molecule by reaction of adsorbed CO with
      another surface O atom, the adsorbed oxygen molecule migrates spontaneously to
      the vacancy site and dissociates with negligible barrier. The role of molecular
      oxygen is to heal the oxygen vacancy rather than being involved in a direct
      reaction with adsorbed CO. The Rh/ CeO2(100) model was found to be inactive for
      CO oxidation, mainly because of the geometric constraints for the adsorbed CO
      molecule to react with one of the surface O atoms, despite the low Ce-O bond
      energy of the CeO2(100) surface. The main reason is the large distance between
      the C of adsorbed CO and the ceria O surface atoms. The particularities of the CO
      oxidation mechanism for isolated Rh atoms on these ceria surfaces are in
      agreement with the experimental activity trends.

PMID- 24015590
TI  - Morphology, dimension, and composition dependence of thermodynamically preferred
      atomic arrangements in Ag-Pt nanoalloys.
AB  - The present article is on Metropolis Monte Carlo simulations coupled with
      semiempirical potentials to obtain the thermodynamically preferred configurations
      of Ag-Pt nanoalloys. The effects of particle size, morphology or alloy
      composition on the surface segregation and the chemical ordering patterns were
      investigated. Surface segregation of Ag is observed in all Ag-Pt nanoalloys. Such
      segregation develops quickly as the increase of particle sizes or global Ag
      composition. Generally, Ag surface enrichment is more apparent for more open
      particles except for large sized icosahedron (ICO) nanoalloys. The most
      energetically favorable chemical ordering patterns gradually evolve from Pt
      core/Ag-shell to onion-like structures when the global Ag composition increases.
      Due to the site preference of Ag segregation, the presence of partly alloyed
      facets and Ag blocked vertices or edges at low global Ag compositions can modify
      the electronic and geometric structures on the nanoalloys' surface. The coupling
      between Pt and Ag sites is a topic of particular interest for catalysis. The
      detailed atomistic understanding of atomic arrangements in Ag-Pt nanoalloys is
      essential to intelligently design robust and active nanocatalysts with a low
      cost.

PMID- 24015591
TI  - General discussion.

PMID- 24015592
TI  - Alumina support and Pdn cluster size effects on activity of Pdn for catalytic
      oxidation of CO.
AB  - A series of model catalysts were prepared by depositing different size Pd(n)
      clusters on alumina films grown to variable thickness on a Ta(110) support.
      Samples were characterized by a combination of X-ray photoelectron spectroscopy,
      low energy He+ scattering, and temperature-programmed reaction and desorption
      (TPR/ TPD). For the activity studies, the samples were first exposed to 18O2 at
      Tox, and then to 13CO at 180 K, where CO sticks to Pd, but not to the alumina
      support. CO oxidation activity increased with increasing thickness of the alumina
      support up to approximately 4.5 nm, but was constant for greater thicknesses.
      Activity increased, with Tox up to 400 K, but then declined for Tox = 500 K.
      Activity was also found to be non-monotonically dependent on deposited cluster
      size, with Pd(n) (n < or = 6) being generally more reactive than the larger
      clusters studied. Activity was only weakly correlated with exposed Pd binding
      sites, which decreased with increasing cluster size, however, there does appear
      to be a correlation between activity and electronic structure, as probed via the
      Pd 3d binding energy. Unlike previous systems we have studied, the activity of
      small Pd(n) on these alumina films was quite stable, with essentially no changes
      observed in up to eight successive TPR experiments.

PMID- 24015593
TI  - Energetics of elementary reaction steps relevant for CO oxidation: CO and O2
      adsorption on model Pd nanoparticles and Pd(111).
AB  - The energetics of elementary surface processes relevant for CO oxidation,
      particularly CO and 02 adsorption, were investigated by a direct calorimetric
      method on model Pd nanoparticles and on the extended Pd(111) single crystal
      surface. The focus of this study lies on a detailed understanding of how a
      nanometer scale confinement of matter affects the binding strength of gaseous
      adsorbates. We report adsorption energies and sticking coefficients of CO and 02
      measured as a function of the adsorbate surface coverage both on pristine and O
      covered Pd surfaces. The reduced dimensions of the Pd substrate were found to
      affect the binding strength of the adsorbates in two principle ways: (i) via the
      change of the local adsorption environment that can result e.g. in stronger
      adsorbate bonding at the particle's low coordinated surface sites and (ii) via
      the contraction of the Pd lattice in small clusters and a concomitant weakening
      of chemisorptive interaction. Particularly for 02 adsorption, the change of the
      adsorption site from a three-fold hollow on Pd(111) to the edge site on Pd
      nanoparticles (approximately 4 nm sized on average) was found to result in a
      strong increase of the Pd-O bond strength. In contrast, CO adsorbs weaker on Pd
      nanoparticles as compared to the extended Pd(111) surface. In total, the binding
      energies of adsorbates on Pd and with this their surface coverages turn out to
      depend in a non-monotonic way on the particular structure of Pd surfaces,
      including the local structure of the adsorption site as well as the global
      properties of the small clusters arising e.g. from the lattice contraction.

PMID- 24015594
TI  - Influence of hot carriers on catalytic reaction; Pt nanoparticles on GaN
      substrates under light irradiation.
AB  - We report the hot carrier-driven catalytic activity of two-dimensional arrays of
      Pt nanoparticles on GaN substrate under light irradiation. In order to elucidate
      the effect of a hot carrier in a catalytic chemical reaction, the CO oxidation
      reaction was carried out on Pt nanoparticles on p- and n-type GaN under light
      irradiation. Metal catalysts composed of Pt nanoparticles were prepared using two
      different preparation methods: the one-pot polyol reduction and are plasma
      deposition methods. Under light irradiation, the catalytic activity of the Pt
      nanoparticles supported on GaN exhibited a distinct change depending on the
      doping type. The catalytic activity of the Pt nanoparticles on the n-doped GaN
      wafer decreased by 8-28% under light irradiation, compared to no irradiation
      (i.e., in the dark), while the Pt nanoparticles on the p-doped GaN wafer
      increased by 11-33% under light irradiation, compared to no irradiation. The
      catalytic activity increased on the smaller Pt nanoparticles, compared to the
      larger nanoparticles, presumably due to the mean free path of hot carriers. Based
      on these results, we conclude that the flow of hot carriers generated at the Pt
      GaN interface during light irradiation is responsible for the change in catalytic
      activity on the Pt nanoparticles.

PMID- 24015595
TI  - Switching-off toluene formation in the solvent-free oxidation of benzyl alcohol
      using supported trimetallic Au-Pd-Pt nanoparticles.
AB  - Trimetallic Au-Pd-Pt nanoparticles have been supported on activated carbon by the
      sol-immobilisation method. They are found to be highly active and selective
      catalysts for the solvent-free aerobic oxidation of benzyl alcohol. The addition
      of Pt promotes the selectivity to the desired product benzaldehyde at the expense
      of toluene formation. Detailed aberration corrected STEM-XEDS analysis confirmed
      that the supported particles are indeed Au-Pd-Pt ternary alloys, but also
      identified composition fluctuations from particle-to-particle which vary
      systematically with nanoparticle size.

PMID- 24015596
TI  - General discussion.

PMID- 24015597
TI  - Concluding remarks.

PMID- 24015599
TI  - Current applications of cardiac troponin T for the diagnosis of myocardial
      damage.
AB  - Biochemical markers of myocardial injury play an important role in the diagnosis
      of cardiovascular diseases. Measurement of cardiac biomarkers is one of the most
      important diagnostic tests in acute myocardial infarction (AMI), heart failure,
      and other cardiovascular disorders. Recently, the European Society of Cardiology,
      the American College of Cardiology Foundation, the American Heart Association,
      and the World Heart Federation have published a consensus definition of AMI that
      includes a detailed guideline for the assessment of biochemical markers in
      suspected disease. The cardiac troponins (cTI and cTnT) were recommended as
      preferred markers of myocardial necrosis in this setting. Herein, we review
      cardiac troponin biochemistry, the performance characteristics of cTnT assays,
      and optimal utilization of troponin in patients with proven or possible
      cardiovascular disease. We also discuss the use of troponin tests, with emphasis
      on cTnT, in different clinical situations in which its levels may be elevated.

PMID- 24015600
TI  - Markers in nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD), the most common liver disorder
      worldwide, encompasses a spectrum of abnormal liver histology ranging from simple
      steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Population
      studies show that NAFLD is strongly associated with insulin resistance, obesity,
      type 2 diabetes mellitus, and lipid abnormalities. In the context of hepatic
      steatosis, factors that promote cell injury, inflammation, and fibrosis include
      oxidative stress, early mitochondrial dysfunction, endoplasmic reticulum stress,
      iron accumulation, apoptosis, adipocytokines, and stellate cell activation. The
      exact NASH prevalence is unknown because of the absence of simple noninvasive
      diagnostic tests. Although liver biopsy is the "gold standard" for the diagnosis
      of NASH, other tests are needed to facilitate the diagnosis and greatly reduce
      the requirement for invasive liver biopsy. In addition, the development of new
      fibrosis markers in NASH is needed to facilitate the assessment of its
      progression and the effectiveness of new therapies. The aim of this chapter,
      which is overview of biomarkers in NASH, is to establish a systematic approach to
      laboratory findings of the disease.

PMID- 24015601
TI  - The expanding role of tandem mass spectrometry in optimizing diagnosis and
      treatment of thyroid disease.
AB  - This review discusses the state-of-the-art measurement of free and total thyroid
      hormones in clinical laboratories. We highlight some of the limitations of
      currently used immunoassays and critically discuss physical separation methods
      for the measurement of free thyroid hormone. Physical separation methods, such as
      equilibrium dialysis or ultrafiltration, followed by tandem mass spectrometry for
      the measurement of free thyroid hormones offer many advantages, which we feel,
      can deepen our understanding of thyroid hormone metabolism and improve patient
      diagnosis and care. Problems with direct analogue immunoassay methods for FT4/FT3
      as well as immunoassay methods for total T3 at low T3 concentrations and during
      pregnancy are highlighted. Improved diagnosis and patient management can be
      achieved utilizing tandem mass spectrometry for these measurements.

PMID- 24015598
TI  - BNP molecular forms and processing by the cardiac serine protease corin.
AB  - The cardiac hormone, B-type natriuretic peptide (BNP), is one of human
      natriuretic peptides which possesses cardiorenal protective actions and is used
      as a therapeutic and a biomarker for heart failure (HF). Its prohormone,
      proBNP1_108, is processed by the proNPs convertases, corin or furin, to inactive
      NT-proBNP1_76 and active BNP1-32. Paradoxically, circulating NT-proBNP and BNP
      are elevated in HF leading to the use of BNP as a sensitive and predictive marker
      of HF. This paradox may be explained by the "nonspecific" nature of conventional
      assays and/or a relative deficiency state of "active BNP" as characterized by an
      increase in inactive proBNP_108 and a decrease in active BNP1-32. Therefore,
      understanding the regulation of proBNP1_108 processing and the role of the
      convertase corin may be important in understanding the physiology of HF. Corin is
      expressed in heart and kidney and may play an important role in regulating blood
      pressure and remodeling of the heart. The processing of proBNP1_108 by corin may
      be controlled by O-linked glycosylation of proBNP1-108. A potential impairment of
      proBNP1lo8 processing in HF may be linked to dysregulation of the convertase
      corin, which may offer therapeutic opportunities to control proBNPlo0s processing
      and its activation in HF.

PMID- 24015602
TI  - Reg proteins and their roles in inflammation and cancer of the human digestive
      system.
AB  - The regenerating gene (Reg) family is a group of small molecules that includes
      four members found in various species, although only three are found in human
      tissues. Their expression is stimulated by certain growth factors or cytokines.
      The Reg family plays different roles in proliferation, migration, and anti
      apoptosis through activating different signaling pathways. Their dysexpression is
      closely associated with a number of human conditions and diseases such as
      inflammation and cancer, especially in the human digestive system. Clinically,
      upregulation of Reg proteins is usually demonstrated in histological sections and
      sera from cancer patients. Therefore, Reg proteins can predict the progression
      and prognosis of cancers, especially those of the digestive tract, and can also
      act as diagnostic markers and therapeutic targets.

PMID- 24015603
TI  - Markers of circulating breast cancer cells.
AB  - The detection of circulating tumor cells (CTC) aids in diagnosis of disease,
      prognosis, disease recurrence, and therapeutic response. The molecular aspects of
      metastasis are reviewed including its relevance in the identification and
      characterization of putative markers that may be useful in the detection thereof.
      Also discussed are methods for CTC enrichment using molecular strategies. The
      clinical application of CTC in the metastatic disease process is also summarized.

PMID- 24015604
TI  - [Biologic effect of novel alternate thermal treatment on breast cancer].
AB  - OBJECTIVE: To develop a novel thermal treatment modality against metastatic
      tumor, and to verify the hypothesis that the extent of tumor angiogenesis damage
      and tumor cell necrosis, accompanied with immune suppression cells relief is
      deterministic to enhance therapeutic effect in the thermal treatment. METHODS:
      The thermal treatment system was developed in our laboratory. The treatment
      including hyperthermia and alternate treatment, were locally applied to 4T1
      murine mammary carcinoma. The extent of tumor necrosis was examined. Further
      investigations were performed to study the changes of MDSCs in peripheral blood
      and spleen. RESULTS: The alternate treatment caused more damage to tumor
      microvasculature and tumor cell necrosis. Immunosuppression cells significantly
      reduced in peripheral blood and spleen. Moreover, it highly increased the
      survival rate of tumor-bearing mice. CONCLUSIONS: The greatest destruction of
      primary tumor induced by the alternate treatment led to a relief of immune
      suppression in tumor bearing mice, and significantly increased therapeutic
      effect, especially for metastatic tumor.

PMID- 24015605
TI  - [Fundus images mosaicking based on edge extended phase correlation].
AB  - With regard to the large amount of calculation in image mosaic algorithm, an
      image mosaic algorithm based on extended phase correlation of edge is presented.
      The improved wavelet edge detection algorithm is to detect edge of blood vessels.
      Then the image translation, rotation and scale changes are calculated by the
      extended phase correlation method. These parameters are utilized to stitch
      images. Finally, image fusion can be achieved by fade-in-fade-out method. It is
      proved by experiments that this algorithm is simple to calculate, and can
      effectively achieve the image mosaic.

PMID- 24015606
TI  - [A positioning method of ultrasound probe in MR system].
AB  - This paper provides a method of positioning the ultrasound probe in MR system.
      Machining 6 slots or cylinder perpendicular to the ultrasound probe surface on
      the edge of ultrasound probe as markers, 12 central cylinder ends are chosen as
      positioning points. By calculating these positioning points' coordinates in MR's
      coordinate system, the coordinate transformation between the ultrasound and MR
      coordinate system can be computed. Furthermore, by taking advantage of redundant
      information, calculating errors can be reduced and the precision can be improved.

PMID- 24015607
TI  - [Perfluoropentane droplets enhanced HIFU therapeutic effect].
AB  - A small HIFU system was used to investigate the phase-shift droplet vaporization
      in vivo and its effect on thermal absorption in tissue-mimicking phantoms. The
      experiments demonstrated that droplets could be vaporized to bubbles in vivo by
      the small HIFU system and the volume of bubbles could increase by tens of times.
      With appropriate droplets concentration, lesion volume produced by HIFU could be
      increased significantly under the same HIFU parameter.

PMID- 24015608
TI  - [Study on the design and detection method of a novel blood pressure measurement
      system].
AB  - A novel blood pressure measurement system was designed which based on
      auscultatory method. And the electret sensor that embedded into the internal
      instrument can detect the Korotkoff-sound signal directly which is coupled by the
      cuff and transmitted in the cross connection. The BP values identification
      algorithm is based on combined detection of Korotkoff-sound and pulse signal, and
      the products of amplitudes and energies are calculated as the characteristic
      values of Korotkoff-sound, and the Korotkoff-sound phases are classified and
      detected by means of clustering of characteristic values, and then BP parameters
      are determined. The contrast test and statistical analysis showed good
      consistency and accuracy between the new BP detection method and conventional
      mercury sphygmomanometer.

PMID- 24015609
TI  - [Realization of DICOM medical image compression technology].
AB  - This paper introduces the implement method of DICOM medical image compression
      technology, The image part of DICOM files are extracted and converted to BMP
      format. The non-image information in DICOM file are stored into the text. When
      the final image of JPEG standard and non-image information are encapsulated to
      DICOM format images, it realizes the compression of medical image, which is
      beneficial to the image storage and transmission.

PMID- 24015610
TI  - [Mining and application of medical equipment basic data].
AB  - OBJECTIVE: In order to realize the medical equipment information management, Need
      based data mining and its application. METHODS: With the help of search engines
      and online translation tools, such as collect basic information, And the data
      mining in information extraction and other methods. RESULTS: To collect
      information on computer and artificial processing, established a professional
      database meets the demand of informatization. CONCLUSIONS: Basic data in the
      application of medical equipment information, make the management more
      convenience, operability and normative.

PMID- 24015611
TI  - [The design of all solid-state tunable pulsed Ti:sapphire laser system].
AB  - This paper presented a design of broadly all solid-state tunable pulsed
      Ti:sapphire laser with high power and stable performance. The laser was pumped by
      custom-made Nd:YAG laser which had water cooling system and amplified by two
      stage amplifier. The method accomplished tunable output of all solid-state
      tunable pulsed Ti:sapphire laser by modifying the reflection angle of the back
      mirror. We investigated the relationship between the power of the pumping laser
      and the all solid-state tunable pulsed Ti: sapphire laser by changing the power
      of the pumping source.

PMID- 24015612
TI  - [Design of a pulse oximeter used to low perfusion and low oxygen saturation].
AB  - This paper presents a new pulse oximeter used to low perfusion at 0.125% and wide
      oxygen saturation range from 35% to 100%. In order to acquire the best PPG
      signals, the variable gain amplifier(VGA) is adopted in hardware. The self
      developed auto-correlation modeling method is adopted in software and it can
      extract pulse wave from low perfusion signals and remove motion artifacts partly.

PMID- 24015613
TI  - [FEA technology applied in the design of CT table].
AB  - In this paper, we develop a method to build FEA model, boundary conditions and to
      analyse static strength and rigidity of the object based on the CT patient table.
      Especially to introduce the examples of how to simplify the actual models to
      ideal models which can easily add some loads. In the end of the paper, we compare
      the results analysis of FEA with the results of experiment and we confirm the
      high accuracy of FEA, so we summarize that FEA technology is very important for
      the development of medical equipment.

PMID- 24015614
TI  - [Design and clinical application of an adjustable spine prone frame].
AB  - The design principle and application of an adjustable spine prone frame are
      introduced. Adjustable spine prone frame is used in posterior lumbar surgery,
      during operation, X-ray can shoot fast and internal fixation implants can fix
      accurately, the vacant abdominal ensure normal respiratory and circulatory
      function, and the lumbar curvature can adjust conveniently. It meets the surgical
      position and care requirements, can prevent the complications effectively.

PMID- 24015615
TI  - [Image processing strategies based on visual attention models under simulated
      prosthetic vision].
AB  - Visual prostheses have the potential to restore partial vision for the blinds.
      The stimulating electrodes generate reproducible phosphenes. Still limited by the
      low resolution vision used in visual prostheses nowadays, it is important to
      optimize the image processing strategies in order to deliver better visual
      information to the patients. This paper presents a review of the current research
      progress on the image processing strategies based on visual attention models
      under simulated prosthetic vision and related psychophysics.

PMID- 24015616
TI  - [The present and future state of minimized extracorporeal circulation].
AB  - Minimized extracorporeal circulation improved in the postoperative side effects
      of conventional extracorporeal circulation is a kind of new extracorporeal
      circulation. This paper introduces the principle, characteristics, applications
      and related research of minimized extracorporeal circulation. For the problems of
      systemic inflammatory response syndrome and limited assist time, the article
      proposes three development direction including system miniaturization and
      integration, pulsatile blood pump and the adaptive control by human parameter
      identification.

PMID- 24015617
TI  - [The classify of fractional photothermolysis laser].
AB  - According to the safety protection of laser, discusses the basis and method of
      classification were discussed the classify of fractional photothermolysis Laser
      was tested and analyzed.

PMID- 24015618
TI  - [In vitro cytotoxicity test of medical ultrasonic couplant].
AB  - The cytotoxicity of medical ultrasonic couplant was tested by MTT assay and agar
      overlay test. By MTT assay, when the inoculum density was high, the cytotoxicity
      level was low, or vice versa. The cytotoxicity grade tested by agar overlay was
      not accord to MTT assay's too. MTT assay is suitable to test the cytotoxicity of
      medical ultrasonic couplant because it is quantitative and more sensitive,
      however, the experimental condition and the preparative method of extraction
      should be determined.

PMID- 24015619
TI  - [Instruction of the technical evaluation for medical devices kits].
AB  - Recent years, the development of medical devices kits is rapid. How to make the
      technical evaluation of medical devices kits more perfect bases on the two major
      principles of safe and effective, and to make kits in the market more normative
      and orderly, these issues for technical evaluation have to be considered. This
      article makes a study on current situation of production, classification of
      management and registration status, combined with existing regulations and
      related standards, and discusses technical evaluation related issues.

PMID- 24015620
TI  - [Discussion about the test method of auditory alarm in YY0709-2009].
AB  - This paper discusses the test method of auditory alarm in YY0709-2009 by
      analyzing the test requirement and process. Consider of the acoustic theory and
      the problem during the test, it provides some suggestions for improvement.

PMID- 24015621
TI  - [Building and application of hospital's electronic film system].
AB  - This paper describes the design process and implementation process of electronic
      film system. The establishment of electronic film system allowed us to
      aggressively reduce film use and costs and to demonstrate a positive return.

PMID- 24015622
TI  - [The establishment and research of ventilator quality control information
      system].
AB  - Ventilator quality control is an important task for the management of hospital
      medical equipment. Analysis the problems of hospital medical device quality
      control and introducing ventilator quality control information system design and
      technical characteristics. The application of the system can improve the
      efficiency of quality control, and enhance hospital medical equipment management
      level.

PMID- 24015623
TI  - [Design and accuracy analysis of upper slicing system of MSCT].
AB  - The upper slicing system is the main components of the optical system in MSCT.
      This paper focuses on the design of upper slicing system and its accuracy
      analysis to improve the accuracy of imaging. The error of slice thickness and ray
      center by bearings, screw and control system were analyzed and tested. In fact,
      the accumulated error measured is less than 1 microm, absolute error measured is
      less than 10 microm. Improving the accuracy of the upper slicing system
      contributes to the appropriate treatment methods and success rate of treatment.

PMID- 24015624
TI  - [Comparison of ArcCheck and film verification for VMAT in the treatment of
      nasopharyngeal carcinoma].
AB  - To compare the performance of ArcCheck and film verification for volumetric
      intensity modulated arc therapy (VMAT) in the treatment of nasopharyngeal
      carcinoma, and to study the feasibility of ArcCheck in VMAT dosimetric
      verification. Five patients of nasopharyngeal carcinoma treated with VMAT were
      enrolled in this study. Dose verification was carried out by ArcCheck and film
      respectively. The result showed that there were no significant differences
      between ArcCheck and film verification. ArcCheck software can obtain three
      dimensional dose distribution directly with simple operation. It is convenient
      for ArcCheck to be used for VMAT dosimetric verification.

PMID- 24015625
TI  - [Dosimetric comparison of treatment plans of pancreatic carcinoma treated with
      body gamma knife and tomotherapy].
AB  - Fourteen patients with pancreatic carcinoma were selected. Two treatment plans
      were designed for each patient, including gamma knife and Tomotherapy. The dose
      characteristics were evaluated by DVH and were compared. The results showed that
      the gamma knife plan had the higher maximal and mean target dose than
      Tomotherapy. Body gamma knife can increase the target dose significantly, and
      decrease the OAR dose. Tomotherapy had excellent dose-target conformality, and it
      can control doses of duodenum and stomach easily, but it had larger low dose
      region.

PMID- 24015626
TI  - [The clinical investigation of the potential complications of H-UPPP surgery in
      removing the partial pharyngeal muscle].
AB  - OBJECTIVE: In order to improve the postoperative effect of modified UPPP,
      removing the partial pharyngeal muscle in surgery, we investigate the
      postoperative effect, the characteristics of pharyngeal cavity and the potential
      complications in OSAHS patients. METHOD: To choose 82 OSAHS patients with
      obstructive oropharyngeal plane diagnosed by Apneagraphy (AG), Fibre
      nasopharyngoscope combined with Muller examination and nasopharyngeal 3D-CT,
      which had completed clinical data inpatients in the anesthesia underwent of the
      partial pharyngeal muscles in the postoperative, divided into a control group of
      26 cases, operating the H-UPPP surgery which did not remove partial pharyngeal
      muscle; The experimental group of 56 cases did a H-UPPP surgical which removed
      partial pharyngeal muscle of possible concurrent symptoms such as nasal
      regurgitation, Eustachian tube dysfunction and other follow-up study in six
      months after the monthly telephone follow-up or outpatient exams to understand
      the disease. Patients were evaluated the sleepiness by ESS(Epworth sleepiness
      scale) in 6 months after the surgery, compared with the preoperative ESS scores,
      do a t test for statistical analysis. AG can be used to evaluate effects of the
      UPPP after 6 months. By measuring uvula length (L1), extent from free edge of
      soft palate to postpharyngeal (L2) and stenosis of nasopharynx width (L3) mean,
      we investigate the characteristics of pharyngeal cavity using the multiple linear
      regression to do the hypothesis test and evaluate the association between
      measuring mean and effect. Using SPSS19.0 software do the preoperative contrast
      analysis. RESULT: After 6 months in surgery, 56 cases in the experimental group,
      effect in 50 cases (89.29%), effective in 6 cases (10.71%); ESS score:
      Preoperative 11.74 +/- 2.48, after the first 6 months 3.84 +/- 2.05. Twenty-six
      cases in control group,effect in 19 cases (73.08%), effective in 7 cases
      (26.92%); ESS score: Preoperative 11.91 +/- 2.40, after the first 6 months 6.92
      +/- 2.47, t-test P value of less than 0.05 between the experimental group and the
      control group; There are no ear fullness, hearing loss, increase their own sound
      which reflect eustachian tube dysfunction and other complications in two groups;
      The function of pharyngeal cavity could be recovered normal lever after 6 months;
      After 6 months of the operation, in the experimental group and the control group
      L1 mean was respectively (5.91 +/- 3.38) mm and (6.20 +/- 3.76) mm (P>0.05); L2
      mean was respectively (15.70 +/- 3.29)mm and (15.35 +/- 1.44) mm (P> 0.05); L3
      mean was respectively (20.54 +/- 3.33) mm and (16.43 +/- 2.21) mm (P<0.05). Nasal
      fauces pitch mean was significantly widened. By the multiple linear regression
      analysis, the postoperative effect has the linear correlation between L2 and 1,3
      residual mean with the negative correlation. Due to the standardized coefficient,
      L3 residual mean has the most influence on the postoperative effect. CONCLUSION:
      Modified UPPP surgery removing the partial pharyngeal muscle is in favor of
      upgrading the postoperative effect with significantly increasing the width of
      postoperative nasal pharyngeal isthmus area, then there are not occur the
      eustachian tube dysfunction, the soft palate function, swallowing and
      articulation function disabled.

PMID- 24015627
TI  - [Research on failure reasons of surgical treatment of obstructive sleep apnea
      hypopnea syndrome and reoperation method].
AB  - OBJECTIVE: To analyze failure reasons of surgical treatment of obstructive sleep
      apnea hypopnea syndrome (OSAHS), and explore the methods of reoperation. METHOD:
      By selecting 27 patients, who accepted surgical treatment for OSAHS and recurred,
      we analyzed failure reasons and obstructive location by apneagraph,
      nasopharyngeal 3D-CT, electronic nasopharynlaryngoscope. Among them, 14 patients
      accepted reoperation, such as uvulopalatopharyngoplasty (UPPP), nasoendoscopic
      surgery, adenoidectomy, partial glossectomy, tracheotomy were applied matching to
      differential obstructive location. AHI, lowest SaO2, Epworth sleepiness scale
      (ESS), complication were recorded after 6 months. RESULT: After 6 months, their
      AHI decreased from 48.19 +/- 13.11 to 11.32 +/- 4. 42, ESS scores decreased from
      12.93 +/- 4.60 to 4.93 +/- 1.44, P<0.05. Two of the 14 patients were cured, while
      the other 12 were efficient. No complications were observed. CONCLUSION:
      Obstructive location judgement and proper surgical operation are the keys of the
      treatment. Preoperative AG sleep monitoring, nasopharyngeal 3D CT, electronic
      nasopharynlaryngoscope examination for determining blocking plane, the decision
      of surgery which is significant.

PMID- 24015628
TI  - [Expression and clinical significance of TLR2 in laryngeal carcinoma tissue].
AB  - OBJECTIVE: To investigate the expression levels of Toll-like receptor 2 (TLR2) in
      laryngeal squamous cell carcinoma (LSCC) tissue and the adjacent normal
      epithelial tissue. METHOD: Reverse transcriptase-polymerase chain reaction(RT
      PCR) and Western-blot were used to detect the expression of TLR2 mRNA and protein
      levels in the tumors and adjacent normal epithelial tissues in 22 patients with
      LSCC, while vocal cord polyps were used as control. RESULT: RT-PCR demonstrated
      that TLR2 mRNA expressed obviously in both of tumor and adjacent tissue, but
      rarely in control. The expression levels of TLR2 mRNA in tumor is higher than
      that in adjacent normal epithelial tissue (t=4.279, P<0.01). It's expression
      intensity was closely related to LSCC clinical stage (F=5.496, P<0.05)and lymph
      node metastasis status (N stage of tumor) (F = 4.271, P<0.05). The protein levels
      of TLR2 were consistent with mRNA expression. CONCLUSION: Both mRNA and protein
      levels of TLR2 were obviously elevated in LSCC, which were associated closely
      with tumor clinical stage and lymph node metastasis. It is indicated that TLR2
      may play an important role by multiple mechanism in laryngeal carcinoma process.

PMID- 24015629
TI  - [Application of harmonic scalpel in Han-uvalopalatopharyngoplasty].
AB  - OBJECTIVE: To investigate the efficacy and feasibility of harmonic scalpel
      assisted Han-uvalopalatoparyngoplasty (H-UPPP) for obstructive sleep apnea and
      hyponea syndrome (OSAHS). METHOD: For each case of 23 patients with OSAHS, the
      left was operated on with traditional method and the right was operated on with
      harmonic scalpel. Operative blood loss, the operation time, postoperative pain,
      the condition of wounds and complications were compared for each case itself.
      RESULT: The operative blood loss, the operation time, of the right with harmonic
      scalpel were much less than the left with traditional method,while no difference
      in postoperative pain, incidence of primary and secondary hemorrhage, the
      condition of wounds was found. CONCLUSION: The application of harmonic scalpel in
      H-UPPP was safe, efficient and feasible, and would have a nice application
      prospect during otolaryngology operations.

PMID- 24015630
TI  - [The discussion on relationship between adenoids hypertrophy and food
      intolerance].
AB  - OBJECTIVE: To explore the relationship between food intolerance and adenoidal
      hypertrophy and accordingly to provide evidence for intolerance and adenoidal
      hypertrophy. METHOD: Adenoidal hypertrophy in patients with a total of 111 cases
      as the experiment group, 30 cases of children with no history of allergies and
      allergy-related diseases and adenoidal hypertrophy symptoms as the control group,
      and compared the result of food intolerance between two groups. RESULT: 1) Food
      intolerance detected positive rate of adenoidal hypertrophy group was higher than
      the control group. 2) The distribution of the two groups of children in the
      extent of food intolerance is different. 3) Adenoid hypertrophy and how many
      types of the food, which is high, moderate intolerance, are unrelated. 4) The
      daily consumption of 14 kinds of food, the top three foods of adenoidal
      hypertrophy group and control group are eggs, milk, cod. CONCLUSION: Food
      intolerance is the possible cause of adenoidal hypertrophy. The detection of
      specific IgG antibodies of food have positive significance in the prevention of
      adenoidal hypertrophy.

PMID- 24015631
TI  - [Study on one stage reconstruction of cranial base defects with ADM].
AB  - OBJECTIVE: The purpose of this study is to explore the effect of reconstruction
      for the nose cranial base defects after removal of tumor with ADM. METHOD:
      Thirteen patients with the nose skull base defects after tumors resection
      underwent cranial base reconstruction with ADM at the same time. Postoperatively,
      routine endoscopic and CT scan were performed on all patients at regular
      intervals. RESULT: The successful cranial base reconstruction was achieved in 13
      patients with ADM. Intracranial infection occurred in 3 patients and recovered
      after two weeks postoperatively, given combination of antibiotics, dexamethasone
      anti-inflammatory, mannitol, reduce intracranial pressure with diuretics and
      cooling, sedation processing. All patients developed no delayed complications.
      CONCLUSION: Our experience has demonstrated that the cranial base reconstruction
      with the ADM "I" shaped sandwich has harvest the satisfactory effect.

PMID- 24015632
TI  - [Clinical study of post-operative pain following coblation tonsillectomy and/or
      adenoidectomy in children with sleep-disordered breathing].
AB  - OBJECTIVE: To explore the characteristics of post-operative pain following
      coblation tonsillectomy and/or adenoidectomy in children with sleep-disordered
      breathing (SDB) and explore the correlation between the first day post-operative
      pain scores and age and operating time. METHOD: 1) A total of 113 SDB children
      scheduled to undergo coblation tonsillectomy and/or adenoidectomy were recruited.
      113 children were divided into two groups according to the method of operation,
      children who underwent coblation tonsillectomy and adenoidectomy were enrolled in
      study group one and children who underwent coblation adenoidectomy only were in
      study group two. Be sides, children of study group one with a history of chronic
      tonsillitis were in chronic tonsillitis group, children without a history of
      chronic tonsillitis were in non-chronic tonsillitis group. 2) The parents scored
      pain in their children on a VAS (anchored by "no pain" at 0 and "worst pain" at
      10) in the morning, before using any analgesics and having breakfast, over the
      first 3 and the seventh post-operative days. 3) Post-operative pain scores were
      compared between both the study group one and two and chronic tonsillitis group
      and non-chronic tonsillitis group. Futhermore, the correlation between the first
      day post-operative pain scores and age and operating time were also analysed.
      RESULT: 1) The difference of post-operative pain scores over the first 3 and the
      seventh post-operative days were significant between the study group one and
      group two (P<0.05). 2) Non-chronic tonsillitis group were significantly less
      painful than chronic tonsillitis group on day 1, day 2 and day 7 (z=-2.004, 
      2.059, -2.334, P<0.05). But there was no significant difference in pain levels on
      day 3 (P>0.05). 3) The first day post-operative pain scores was correlated with
      age (r=0.273, P<0.01) and operating time (r=0.423, P<0.01). CONCLUSION: The first
      day post-operative pain scores was correlated with age and operating time.
      Children with a history of chronic tonsillitis were more painful than children
      without the history.

PMID- 24015633
TI  - [Fourth branchial pouch sinus of children: from diagnosis to techniques and
      technology of surgical operation].
AB  - OBJECTIVE: To clarify the correct diagnostic methods of FBPS of children, and to
      explore techniques and technology of surgical operation aim to complete excision
      of sinus tract and preservation of the recurrent laryngeal nerve through
      analyzing the clinical characteristics and the characteristics of open neck
      surgery in FBPS of children. METHOD: Clinical materials of 6 children FBPS with
      internal pyriform sinus were retrospectively analyzed, and literatures were
      studied to explore the appropriate surgical management of children FBPS; lesions
      of 6 patients were completely dissected by open neck surgery with the help of di
      direction catheterization revealing the tract of fistula, and the openings of the
      fistula to pyriform apex were cauterized by monopolar coagulation at the end of
      the procedure; all 6 cases were with systematic endoscopic follow-up. RESULT: All
      cases of 6 children patients were cured by open neck surgery, no recurrence of
      clinical symptoms were observed during a mean follow-up of 14 months (1-3 years);
      2 cases were diagnosed with an "anatomical" relapse (persistence of the sinus
      tract orifice without clinical symptoms) at the follow-up endoscopy(at 3 and 4
      months after surgery); all 6 cases had no complication of laryngeal paralysis.
      CONCLUSION: The children patients presenting recurrent acute suppurative
      thyroiditis and deep neck abscess of anterior area in the lower part of neck,
      especially locating left neck, should be considered as the diagnosis of FBPS.
      also the same as confirmed by enhanced neck CT scan and direct laryngoscopy.
      Patients with identification of internal pyriform sinus and Betz fold by direct
      laryngoscopy, and with identification of fistula which passes through the
      cricothyroid membrane beneath the superior laryngeal nerve can be confirmed FBPS.
      Completely dissection of sinus tract by open neck surgery was the effective
      management of children FBPS and di direction catheterization aids to reveal and
      identify the tract of fistula. Resection of the posterior part of the thyroid
      cartilage ala can be useful to aid exposure and preservation of the recurrent
      laryngeal nerve; but co-excision of a portion of the upper of the thyroid gland
      aids to the entire dissection of lesions. In addition, cauterizing the opening of
      the fistula to pyriform apex may be useful to obliterate the internal opening of
      pyriform sinus.

PMID- 24015634
TI  - [Levels of serum IL-4, IFN-gamma, IL-32 in children with juvenile-onset recurrent
      respiratory papillomatosis].
AB  - OBJECTIVE: To explore the relationship between serum IL-4, IFN-gamma, IL-10
      levels and the aetiology of juvenile-onset recurrent respiratory papillomatosis.
      METHOD: Serum IL-4, IFN-gamma, IL-32 levels of 15 JORRP children were detected by
      use of enzyme-linked immunosorbent assay (ELISA) and compared with those of
      healthy control group. RESULT: Serum IL-4 levels were significantly higher in the
      JORRP children (P<0.01): (524.65 +/- 147.77)pg/ml in the JORRP children and
      (213.27 +/- 87.48) pg/ml in the healthy control group. Serum IFN-gamma levels
      were significantly lower in the JORRP children (P<0.01): (2.87 +/- 0.84) pg/ml in
      the JORRP children and (10.63 +/- 5.09) pg/ml in the healthy control group. Serum
      IL-32 levels were significantly lower in the JORRP children (P< 0.01): (2.47 +/-
      1.60) pg/ml in the JORRP children and (9.08 +/- 2.66) pg/ml in the healthy
      control group. CONCLUSION: 1) While the concentration of Th2 like cytokine IL-4
      in children with JORRP was higher than that in control group, the concentration
      of Th1 like cytokine IFN-gamma in children with JORRP was lower than that in
      controls, indicating that the polarization of Th1 /Th2 T cell in children with
      JORRP; 2) The polarization of Th1/Th2 T cell may cause the reduction of the serum
      IL-32 as a proinflammatory role in host immunity system that could not eradicate
      HPVs because of lacking enough inflammatory stimulation.

PMID- 24015635
TI  - [The application of mitomycin C in treatment of airway scarring stenosis].
AB  - OBJECTIVE: To explore the feasibility and efficacy of mitomycin C(MMC) in the
      treatment of airway scarring stenosis. METHOD: The clinical materials of 11
      patients with airway stenosis treated with MMC from 2008 to 2012 were analyzed
      retrospectively,including atresiaofnasopharynx/choanal atresia (2 cases),
      pharyngostenosis (1 case), and laryngotracheal stenosis (8 cases). All were
      treated with endoscopic surgery under general anesthesia. Patients received
      topical application of MMC (0.4 mg/ml) to the lesion for 5 minutes after the scar
      tissue removed and repeated five times. RESULT: No patients occurred restenosis
      in 2 months' follow-up postoperative. Two patients with
      atresiaofnasopharynx/choanal atresia achieved satisfactory ventilation outcome, 8
      patients with laryngotracheal stenosis decannulated successfully, 1 patients with
      pharyngostenosis achieved near normal deglutition. CONCLUSION: MMC in endoscopic
      airway surgery is safe and effective in the treatment of airway stenosis and
      offers a high success rate for patients with grade 1-2 stenosis. It should be
      used as a first method in the treatment of airway stenosis.

PMID- 24015636
TI  - [The effect of low-temperature coblation under endoscopy on infantile subglottic
      hemangioma].
AB  - OBJECTIVE: To evaluate the effect of low-temperature coblation on subglottic
      hemangioma under endoscopy. METHOD: Clinical data of 5 patients whom were
      diagnosed as subglottic hemangioma treated with low-temperature coblation under
      endoscopy were retrospectively studied. Two cases of the patients were treated
      after tracheotomy. RESULT: Hemangioma vanished completely in the 5 patients. All
      patients were followed-up from 3-6 months,no recurrence was found, and the 2
      cases were extubated successfully. CONCLUSION: Endoscopic surgery u sing low
      temperature coblation for subglottic hemangioma after tracheotomy can relief the
      airway obstruction quickly, shorten the nature course of hemangioma and the
      period of wearing trachea,also no complication such as subglottic stenosis which
      is thought to be a safe and effective therapy for large size hemangioma. While
      for small size hemangioma, endoscopic surgery using low-temperature coblation
      under good total anesthesia without tracheotomy combined is effective, less
      injure, and suitable. Endoscopic surgery using low-temperature coblation for
      subglottic hemangioma has following advantages such as simplicity, minimal
      invasion and so on. It is a viable surgical method for the treatment of
      subglottic hemangioma.

PMID- 24015637
TI  - [How to choose the method for imaging diagnosis of foreign body of trachea in
      children].

PMID- 24015638
TI  - [The clinical application experiences of laryngeal mask in otolaryngology
      surgery].

PMID- 24015639
TI  - [Application of pectoralis major myocutaneous flap to reconstruction of defects
      in head and neck cancer].

PMID- 24015640
TI  - [The experiences of debridement through external cervical incision in patients
      with tuberculous retropharyngeal abscess].

PMID- 24015641
TI  - [Wide chondrosarcoma of the larynx in female: a case report].
AB  - A case of a 67-years-old female with well-differentiated chondrosarcoma of the
      left lamina of the thyroid cartilage, cricoid cartilage and arytenoid cartilage
      is reported, in which a total arytenoidectomy and partial resection of the left
      thyroid cartilage and cricoid cartilage were performed. The postoperative course
      has been successful except for the existence of a tracheal stoma and slight
      hoarseness. There has been no evidence of recurrence or metastasis in 6 years of
      follow-up.

PMID- 24015642
TI  - [Partial tonsillectomy].
AB  - The feasibility of partial tonsillectomy was reviewed. Compared with total
      tonsillectomy, partial tonsillectomy has the advantages of less postoperative
      pain, lower postoperative bleeding rate and faster recovery. Partial
      tonsillectomy has a potential for tonsil regrowth and its efficacy in treating
      sleep-disordered breathing in children is still controversial.

PMID- 24015643
TI  - [Current situation and development in treatment of laryngopharyngeal reflux].
AB  - The mainstay of treatment of laryngopharyngeal reflux focuses on a concoction
      involving proton-pump inhibitor and modified beneficial behaviors, sometimes
      referring to medications like H2-R blocker etc. Therapeutic effect seems to be
      promising although may at times be challenged by conflict researches. Voice
      therapy and voice parameters emerge to provide a grand new perspective in
      treatment and evaluation of this disease.

PMID- 24015644
TI  - [Standardized evaluation and treatment of patellar fractures].

PMID- 24015645
TI  - [Case-control study on the treatment of patellar fracture with "8" tension band
      wire fixation either by percutaneous or open reduction].
AB  - OBJECTIVE: To study the clinical efficacy of the treatment of patellar fracture
      percutaneous or open reduction with "8" tension band wire fixation. METHODS: From
      July 2007 to April 2010,96 patients with patellar fracture were treated by
      percutaneous or open reduction with "8"tension band wire fixation. In
      percutaneous group,there were 28 males and 20 females with an average age of
      (53.8 +/- 4.7) years old (ranged, 21 to 84); there were 27 transverse fractures
      and 21 comminuted fractures. In open reduction group, there were 26 males and 22
      females with an average age of (49.1 +/- 4.2) years old (ranged, 19 to 86); there
      were 25 transverse fractures and 23 comminuted fractures. The operation time,
      hospital stay, and pain score on the first day and one week after operation were
      compared, and Bostman score was compared too. RESULTS: All patients were followed
      up with an average of 13 months ranging from 6 to 19 months. The mean operation
      time of percutaneous group was (53.0 +/- 4.3)min and the open reduction group was
      (49.0 +/- 3.1) min, and there was no statistic differences between two groups (P
      > 0.05). The hospital stay, healing time in percutaneous group was shorter than
      that of open reduction group; VAS score on first day and the first week after
      operation in percutaneous group was lower than that of open reduction group. The
      mean Bostman score in percutaneous group (28.8 +/- 4.7) was lower than open
      reduction group (24.6 +/- 4.3). CONCLUSION: Percutaneous internal fixation for
      the treatment of patellar fracture has advantages of minimally invasive, quick
      recovery. The clinical effectiveness of this method is superior to the open
      reduction.

PMID- 24015646
TI  - [Case-control study on patellar fixed pin and Kirschner's nail with tension band
      for the treatment of patellar fracture].
AB  - OBJECTIVE: To compare the clinical efficiency of patellar fixed pin and
      Kirschner's nail with tension band in treating patellar fracture. METHODS: From
      November 2010 to January 2012, the clinical data of 42 patients with patella
      fracture were treated with patella fixed needle and Kirschner's nail with tension
      band. The patellar fixed needle group included 21 cases (14 males and 7
      females,aged 26 to 65 with an average of 43.6 years old); The Kirschner's nail
      with tension band group included 21 cases (12 males and 9 females,aged 32 to 58
      with an average of 41.5 years old). The operation time, intra-operative blood
      loss and healing time were compared between two groups. Bostman score was applied
      to compare the therapeutic effects. RESULTS: All patients were followed up with
      an average of 11.5 months ranged from 6 to 14 months. The fractures healed well
      without complications such as nonunion and infection. According to Bostman score,
      there was no significant difference between two groups in clinical efficiency (Z
      = -0.83, P = 0.407). There was significant difference in operation time (t =
      6.67, P = 0.00), while no difference in intra-operative blood loss, bone healing
      time (t = 1.90, P = 0.064; t = 0.612, P = 0.544). CONCLUSION: Both methods can
      obtain good results. However, patellar fixed pin combined with tension band is
      one of the ideal methods for the treatment of patellar fracture, it has an
      advantage of simple with shorter operation time, rigid fixation, less
      complications and well recovery.

PMID- 24015647
TI  - [Application of Ni-Ti patellar concentrator combined with Herbert screw and
      wirerope for the treatment of comminuted patellar inferior pole fractures].
AB  - OBJECTIVE: To evaluate the surgical techniques and clinical effect of Ni-Ti
      patellar concentrator combined with Herbert screw and wirerope in treating
      comminuted patellar inferior pole fractures. METHODS: From March 2008 to June
      2010,34 patients with comminuted patellar inferior pole fracture were treated
      with Ni-Ti patellar concentrator combined with Herbert screw and wirerope. Of
      them, there were 19 males and 15 females with an average age of 38.6 years
      old(ranged from 22 to 75). Early functional exercise was guided postoperatively
      and the patients were regularly followed up and their outcomes were assessed.
      RESULTS: All patients were followed up with an average of 13.5 months (ranged,7
      to 20). All fractures healed. According to Bostman Clinical Rating System, the
      average score was 28.43 +/- 2.34,and excellent results in 21 cases,good in 13
      cases and no poor case. CONCLUSION: Ni Ti patellar concentrator combined with
      Herbert screw and wirerope for the treatment of comminuted patellar inferior pole
      fracture is an effective method and of great value to clinical application.

PMID- 24015648
TI  - [Surgical treatment for multi segmental cervical spondylosis myelopathy through
      anterior approach].
AB  - OBJECTIVE: To explore clinical effects of multi-segmental cervical spondylosis
      myelopathy through anterior approach by surgical treatment. METHODS: From
      September 2006 to September 2012, the data of 85 patients with multi segmental
      cervical spondylosis myelopathy were retrospectively analyzed. Among them, 48
      cases were male, 37 cases were female, ranging the age from 34 to 86 years old
      (mean, 54.5 years old). Surgical procedure included anterior discectomy and
      fusion (19 cases), anterior secondary discectomy and fusion (45 cases) and
      anterior discectomy combined with anterior cervical corpectomy with fusion (21
      cases). Bone fusion were evaluated by X-ray at the 3rd day after operation and
      following up. JOA score and improvement rate were compared. RESULTS: All patients
      were followed up from 6 to 30 months with an average of 18 months. Decompression
      were done throughly during operation and good intervertebral space height and
      cervical curvature were obtained. X-ray showed nonunion in 3 cases, and
      improvement rate was 96%. JOA score after operation was higher than before
      operation, and had significant differences (P < 0.05). Fifty-six cases got
      excellent results, 16 moderate, 9 effective and 4 invalid according to JOA
      scores. CONCLUSION: Surgical procedures for cervical spondylosis myelopathy
      should be chosen reasonably in accordance with sympotoms, signs, imaging data, so
      as to obtain good results in decompression, recoving intervertebral height and
      cervical curature, improving fusion rate.

PMID- 24015649
TI  - [Clinical application of advanced percutaneous vertebroplasty in treating of
      senile osteoporotic vertebral compression fracture].
AB  - OBJECTIVE: To compare the differences between advanced percutaneous
      vertebroplasty and routine percutaneous vertebroplasty,and evaluate the clinical
      application of advanced percutaneous vertebroplasty in treating senile
      osteoporotic vertebral compression fracture. METHODS: From January 2010 to
      January 2011,28 patients with senile osteoporotic vertebral compression fracture
      were concealed random allocated to advanced percutaneous vertebroplasty and
      routine percutaneous vertebroplasty group according to whether using advanced
      percutaneous pedicle puncture. Of them,there were 5 males and 23 females with an
      average age of (70.50 +/- 9.33) years old (ranged, 53 to 85). Course of disease
      was from 2 to 28 days with an average of (7.62 +/- 4.52). The fracture involved
      34 vertebral bodies (19 segments of thoracic vertebrae and 15 segments of lumbar
      vertebra), 3 day's antibiotics were applied to prevent infections. The opreation
      time, X-ray fluoroscopy times were compared, and pain relief effect were
      evaluated by VAS (visual analogue scales) score. RESULTS: For operation time,
      there were significant meaning between routine group (49.00 +/- 7.74) min and
      advanced group (32.36 +/- 4.81) min (t = 6.828,P = 0.000 < 0.05); X-ray
      fluoroscopy times in advanced group (4.28 +/- 1.38) times was shorter than
      routine group (8.78 +/- 2.33) times, and had statistical significance (t = 6.222,
      P = 0.000 < 0.05); while there were no meaning in VAS scores between routine
      group (2.85 +/- 0.94) and advanced group (2.57 +/- 1.08) (t = 0.740, P = 0.456 >
      0.05). CONCLUSION: Compared with routine group, advanced group can shorten
      opreration time, reduce radiological hazard, further reduce image monitoring
      costs and surgical risk, and benefit from the application of advanced
      percutaneous vertebroplasty in treating senile osteoporotic vertebral compression
      fracture. Furthmore, it can provide reference to vertebral body biopsy and
      minimally invasive of pedicle screw fixation.

PMID- 24015650
TI  - [Clinical classification of gluteal muscle contracture under arthroscopy].
AB  - OBJECTIVE: To explore clinical effects of gluteal muscle contracture and minimum
      invasive surgery under the arthroscopy. METHODS: Totally 358 patients with
      gluteus contracture were treated,which included 175 males and 183 females with an
      average age of (19.7 +/- 6.8) years old (ranged, 14 to 41). All patients have a
      history of repetitive intramuscular injection of penicillin with benzyl alcohol
      solvent. According to clinical characteristics and intraoperative situation,
      patients were classified into four groups:cable strip (118 cases), fanshaped (107
      cases), mixed (87 cases), tensor fasciae latae contracture(46 cases). The
      curative effects were evaluated according to postoperative function evaluation
      standard of gluteus contracture. RESULTS: All patients were followed up and 37
      cases withdrew. The following up time ranged from 1.5 to 8 years with an average
      of 3.5 years. According to evaluation standard of gluteus contracture, 303 cases
      got excellent results, 13 cases good,and 5 cases fair at the final follow-up. No
      recurrence, infection and neurovascular injury occurred. CONCLUSION: The
      classification of gluteal muscle contracture is beneficial for choose surgical
      strategy and improve curative effect. The advantage of plasma knife minimally
      invasive solution in treating gluteal muscle contracture with radiofrequency
      under arthroscopy is minimally invasive, safe, and benefit for early functional
      exercises.

PMID- 24015651
TI  - [Diagnosis and management for the non-traumatic epidural sequestered cervical
      disc extrusion].
AB  - OBJECTIVE: To explore the clinical characteristics and management of non
      traumatic epidural sequestered cervical disc extrusion. METHODS: From January
      2002 to July 2011, the clinical data of 10 patients with non-traumatic epidural
      sequestered cervical disc extrusion were treated by anterior cervical mostly
      vertebraectomy and nucleus pulposus removal after decompression and internal
      fixation through longitudinal ligament resection. Of them,there were 6 males and
      4 females with an average age of 48.2 years old (ranged from 42 to 65), the
      course of disease ranged from 1 month to 4 years (mean, 15 months). All patients
      manifested numbness and weakness of four limbs, unstable walking and sphincter of
      oddi dysfunction. Preoperative MRI showed segmental cervical spinal cord
      compression. JOA scoring criteria was applied to evaluate preoperative and follow
      up neurologic function. RESULTS: Ten patients were followed up, and the duration
      ranged from 15 to 32 months, with an average of 21 months. No complications
      related to opreation occurred. Preoperative MRI showed nucelus puplposus
      sequestered longitudinal ligament were on equal signal on T1-weighted and
      corresponding pathological,while it showed equal and high signal on T2-weighted.
      JOA score were increased from 7.20 +/- 1.55 preoperative to 13.60 +/- 1.90
      postoperative (t = -11.8, P < 0.001), and excellent in 3 cases, good in 6 cases
      and moderate in 1 case. CONCLUSION: Anterior cervical mostly vertebraectomy and
      nucleus pulposus removal after decompression and internal fixation through
      longitudinal ligament resection after early diagnosis is the key to success of
      treating non-traumatic epidural sequestered cervical disc extrusion.

PMID- 24015652
TI  - [Spinal fixed-point rotating reduction in treating lumbar disc herniation by
      three-dimensional MRI].
AB  - OBJECTIVE: To observe three-dimensional space position change of nucleus pulposus
      and nerve root before and after treatment of lumbar disc herniation by spinal
      fixed-point rotating reduction, and explore the mechanisms. METHODS: Totally 52
      patients with L5S1 lumbar disc hernation treated by spinal fixed-point rotating
      reduction were collected from April 2009 to June 2011. There were 33 males and 19
      females with an average age of 34.6 years old (ranged, 19 to 55). Three
      dimensional MRI were performed to observe relationship between nucleus pulposus
      and related nerve root,configuration change of spine and pelvic on coronary MRI.
      RESULTS: MRI showed relationship between nucleus pulposus and related nerve root
      mainly located on axillary, shoulder, front and surround. Vertebral displacement
      disappeared, lumbocrural pain alleviated after manipulative therapy. All patients
      were followed up from 2 to 28 months with an average of 12 months, and no
      recurred. All patients recovered work. Nucleus pulposus had no change,while
      lumbral spinal and pelvic curve changed before and after admission. CONCLUSION:
      Lumbar disc herniation combined with single (multiple) vertebral displacement,can
      cause biomechanical properties of nucleus puplosus and related nerve root, while
      spinal fixed-point rotating reduction can correct vertebral displacement, recover
      balance between inside and outside of spinal.

PMID- 24015653
TI  - [Different biological characteristics between nucleus pulposus and annulus
      fibrosus cells in rabbits].
AB  - OBJECTIVE: To compare biological characteristics between nucleus pulposus and
      annulus fibrosus cells in vitro model. METHODS: Five New Zealand white rabbits (2
      to 3 kg, either gender) were isolated nucleus pulposus and annulus fibrosus under
      sterilized condition, then cultured in nutrient solution with 15% FBS and
      DMEM/F12 (1:1) by enzyme digestion combined with tissue block method. When 90%
      cells fused, subcultring were performed. Cell morphology were observed by
      inverted phase contrast microscope, cell viability were detected by trypan blue
      staining, histological were observed by a toluidine blue and HE staining, cell
      proliferation were tested by MTT method, then the cell morphology, viability,
      proliferation between nucleus pulposus and annulus fibrosus were compared.
      RESULTS: There were no obviously differences between nucleus pulposus and annulus
      fibrosus in original and the first strain. Physalides were appeared in annulus
      fibrosus on the second generation. The strapping time was later, and activity was
      lower in nucleus pulposus than annulus fibrosus. The growth of cell proliferation
      in nucleus pulposus was lower than annulus fibrosus from the ninth day.
      CONCLUSION: The cell activity in annulus fibrosus is higher than nucleus
      pulposus. Digenerative disc disease may caused by recession of nucleus
      pulposus,local biomechnical changes, furether caused structure change and
      function loss of annulus fibrosus.

PMID- 24015654
TI  - [Effects of Yiqi Huayu prescription on knee cartilage degeneration in HIF-1alpha
      gene knockout mice].
AB  - OBJECTIVE: To study the role of hypoxia-inducible factor 1 alpha (HIF1alpha) on
      knee cartilage degeneration,and to explore the effects and mechanisms of Chinese
      herbal compound Yiqi Huayu prescription on HIF-1alpha gene knockout mice on knee
      cartilage degeneration. METHODS: The 4-month and 6-month HIF-1alpha gene knock
      out mice were obtained by interbreeding, and divided into HIF-1alpha +/+ 4-month
      mice group,HIF-1alpha -/- 4-month mice group,HIF-1alpha +/+ 6-month mice group
      and HIF-1alpha -/- 6-month mice group, 3 mice in each group. And then the 2-month
      old HIF-1alpha gene knock out mice were randomly divided into Yiqi Huayu
      prescription group and physiological saline group. There were 6 mice in each
      group. After 2 months' drug administration, the knee joint of mice was collected,
      and the Mankin score were evaluated; Safranine-fast green staining, HE Staining,
      and immunohistochemistry analysis for VEGF, Col X, Col II, MMP-13 and Sox-9 were
      performed erespectively. RESULTS: (1) Compared to the results in the HIF
      1alpha+/+ mice groups, the HIF-1alpha-/- mice developed aging related cartilage
      loss and bony tissue appearance, cartilage defects increased,and cells reduced.
      In HIF-1alpha-/-4-month mice and 6-month mice group, the expresion of Col II and
      Sox9 decreased, and the expression of Col X, MMP-13 and VEGF increased. (2)
      Compared to the physiological saline group, the ossification and defect of knee
      joint cartilage reduced of mice in the Yiqi Huayu prescription group, the
      cartilage cell distribution was more uniform, and the total number of cells
      increased. The expression of type II collagen and Sox9 protein increased,
      expression of Col X, MMP-13 and VEGF protein decreased of mice in the Yiqi Huayu
      prescription group. CONCLUSION: The knee cartilage degenerates in the HIF-1alpha
      cKO mice, and the degeneration increased with age adding. The Yiqi Huayu
      prescription can delay the degeneration of knee cartilage of HIF-1alpha cKO mice.

PMID- 24015655
TI  - [Clinical effect of posterior atlanto axial vertebra internal fixation for
      treatment of instability of occipitocervical].
AB  - OBJECTIVE: To explore radiographic results and clinical effects of posterior
      atlanto axial vertebra internal fixation in treating instability of
      occipitocervical. METHODS: The clinical data of 155 patients with instability of
      occipitocervical treated by posterior atlanto axial vertebra internal fixation
      were respectively analyzed from September 2005 to January 2011. There were 68
      males and 87 females, ranging in age from 6 to 75 years old with an average of
      45.6 years old. Of them, 53 cases were fresh odontoid fractures(Aderson type II
      C), 30 cases were os odontoideum, 20 cases were old odontoid fractures, 18 cases
      were unstable atlas fractures, 12 cases were atlanto axial rotatory dislocation,
      11 cases were atlanto axial dislocation after rheumatoid arthritis, and 11 cases
      were basilar invagination. Radiographic results were evaluated in terms of atlas
      pedicle screw fixation, bone healing and bone graft fusion. Clinical effect
      evaluation included relief of pain in the occipital-cervical region by VAS score
      and JOA score. RESULTS: Totally 300 screws were set through atlas pedicle screw
      fixation in 150 patients. Five patients receivde hook fixation. Postoperative CT
      showed ideal nailing were 275 (91.7%),acceptable nailing were 14 (4.7%) and
      unacceptable nailing were 11 (3.6%). All patients were followed up, and the
      duration ranged from 16 to 40 months with an average of 25.4 months. The fresh
      fractures healed and 140 cases got bone graft fusion. Preoperative VAS and JOA
      score were respectively improved from (7.2 +/- 1.1), (7.3 +/- 2.4) to (3.2 +/-
      1.1), (13.3 +/- 2.4) at the latest follow-up. CONCLUSION: Posterior atlanto axial
      vertebra internal fixation in treating instability of occipitocervical can
      effectively recover physiological curvature of cervical, provide mechanical
      stability, and obtain good clinical effect. For the young patients who require
      further activity, posterior fixation and non-fusion technology is a good choose,
      which can avoid bone graft.

PMID- 24015656
TI  - [Imaging measurement of anterior internal fixation for the cervicothoracic
      junction and its clinical significance].
AB  - OBJECTIVE: To measure important parameters of anterior internal fixation for the
      cervicothoracic junction by us-ing imaging measurement, and provide reference for
      cervicothoracic junction surgery and design of steel plate screw internal
      fixation. METHODS: From June to November 2012, 120 health people's median
      sagittal plane MRI of cervical spine were ran-domly collected. Of the 120 cases,
      there were 58 males and 62 females with an average age of 48.3 +/- 13.7, ranging
      the age of 20 to 78 years old. The anterior,middle and posterior height of
      vertebral, anterior, upper, medium and lower sagittal diameter, an-terior height
      of different segments and Cobb angle were measured by measuring machine in the
      PACS system. RESULTS: The an-terior, middle and posterior height of vertebral,
      medium and lower sagittal diameter gradually increased from cranial to caudal of
      cervicothoracic junction (P < 0.01). For single vertebral,posterior>
      anterior>middle height (P < 0.01), lower > upper>medium sagittal diameter (P <
      0.01). The lower sagittal diameter of upper vertebral body was close to upper
      sagittal diameter of lower vertebral body. Cobb angle of male was (7.61 +/- 3.85)
      degrees, while female's was (5.58 +/- 2.59) degrees . CONCLUSION: During the
      anterior in-ternal fixation of cervicothoracic junction, it is suggested that the
      entry points of upper vertebral body should locate on the lower and middle 1/3 of
      vertebral body, and screws could slightly incline towards cranial,the entry
      points of lower vertebral body should locate on the upper and middle 1/3 of
      vertebral body, while screws could slightly incline towards caudal, also can be
      prebent according to Cobb angle of health.

PMID- 24015657
TI  - [Understanding and diagnosis of "Gu Cuo Feng and Jin Chu Cao].
AB  - Traditional Chinese Medicine believes that "Gu Cuo Feng and Jin Chu Cao "is the
      key pathogenesis for spinal degenerative disease, such as cervical spondylosis,
      but there is also lots of controversy for the concept of "Go Cuo Feng and Jin Chu
      Cao". The paper emphasizes the concept of "Cu Cuo Feng and Jin Chu Cao" from
      structural abnormality and dysfunction, and build the clinical standard of
      cervical "Gu Cuo Feng and Jin Chu Cao" from clinical symptoms, conventional
      physical signs of cervical spondylosis, special physical signs (mainly by
      palpation) and imaging measurement (special measuring method).

PMID- 24015658
TI  - [Mid-long-term curative effect analysis of complex acetabular fracture].
AB  - OBJECTIVE: To discuss clinical effects of complex acetabular fracture. METHODS:
      From January 2005 to December 2010, totally 31 patients with complex acetabular
      fracture received surgery. There were 21 males and 10 females with an average age
      of 38.6 years old (ranged, 31 to 57). X-ray, CT, operation scheme and clinical
      efficiacy were retrospectively analyzed. American Academy of Orthopaedic Surgery
      standard was used to evaluate hip joint function. RESULTS: All patients were
      followed up from 12 to 36 months with an average of 17.6 months. No complications
      and neurovascular injury occurred. One case received total hip replacement
      arthroplasty. There were 17 cases obtained anatomical reduction, 12 cases got
      satisfied reduction and 2 cases not satisfied. According to American Academy of
      Orthopaedic Surgery standard, 18 cases got excellent result, good in 9 cases,
      fair in 3 cases and poor in 1 case. CONCLUSION: Complex acetabular fracture
      combine with lots of complications and easily had occurre postoperative
      complications. It can improve curative effect by accurate reduction and reliable
      fixation and maximize restoring function of hip joint.

PMID- 24015659
TI  - [Retrospective study on the treatment of ankylosing spondylitis with cervical
      spine fracture: 8 cases report].
AB  - OBJECTIVE: To discuss surgical procedures and curative effect of ankylosing
      spondylitis with cervical spine fracture. METHODS: From January 2003 to October
      2011, 8 patients with ankylosing spondylitis with cervical spine fracture were
      respectively treated by surgical treatment (7 cases) and conservative treatment
      (1 case), 8 cases were male with an average of age 41 years old (ranged, 27 to
      49). All patients were confirmed by CT and MRI,and 6 cases combined with spinal
      cord injury. One case was treated with skull-neck-thorax model, 7 cases were
      treated by surgery. The procedures included anterior approach (5 cases),
      posterior approach (1 case), and combined anteroposterior approach (1 case).
      Fracture fusion condition were evaluated according to CT at the final following
      up, improvement of spinal cord injury were assessed according to Frankel
      classification. RESULTS: Eight patients were followed up from 4 to 38 months with
      an average of 34 months. Seven cases obtained bone healing, 3 patients without
      spinal cord injury remained intact after operation, 5 patients with spinal cord
      injury improved at different degree after operation. Frankel classification of 7
      patients were improved 1 degree, and 1 case delayed union for following up.
      CONCLUSION: Ankylosing spondylitis with cervical spine fracture is a special kind
      of trauma, which have a high rate of neurological deficits. Surgery should be
      performed as early as possible, and procedures were chosen depending on
      particular case.

PMID- 24015660
TI  - [Preoperative traction of calcaneus in the treatment of Ruedi-Allgower II and III
      pilon fracture].
AB  - OBJECTIVE: To explore the role of preoperative calcaneal traction in the
      treatment of Ruedi-Allgower II and III Pilon fracture. METHODS: From March 2005
      to March 2010, 56 patients with Ruedi-Allgower II and III Pilon fracture were
      treated by calcaneal traction internal fixation on the second phase. There were
      42 males and 14 females with an average age of 34.6 years old (ranged 18 to 68).
      Clinical outcomes were assessed according to Tormette Pilon and tibia fracture
      standard. RESULTS: All patients were followed up from 9 to 36 months with an
      average of 18 months. All fracture obtained bone healing, the time ranged from
      4.5 to 8.2 months with a mean of 6.2 months. No deep infection, breakage of
      internal fixation and other complications occurred. According to Tornetta
      evaluation criteria,35 cases got excellent results, 18 cases good,and 3 cases
      fair. CONCLUSION: Preoperative calcaneal traction as a temporary fixing measure
      can provide a good environment for successful operation, and is an essential
      foundation for recovering functional, painless, load, movable joint.

PMID- 24015661
TI  - [Isolated complete scaphoid dislocation: a case report].

PMID- 24015662
TI  - [Surgical treatment of acetabular type C1 acetabular fracture by posteroproximal
      posteroanterior sequential reduction and internal fixation].
AB  - OBJECTIVE: To investigate the operative reduction techniques and clinical results
      of surgical treatment of type C1 (AO/ASIF) acetabular fracture by posteroproximal
      posteroanterior sequential reduction and internal fixation. METHODS: From August
      2004 to January 2012, 13 patients with type C1 (AO/ASIF) acetabular fracture were
      treated by posteroproximal-posteroanterior sequential reduction and internal
      fixation. Of them, 8 cases were male and 5 cases were female with an average age
      of 42 years years old (ranged, 18 to 64). Pelvis 3-dimentional CT reconstruction
      were used to confirmed the classification of fracture, and the operation were
      performed during from 5 to 20 days with an average of 9.5 days. Operation time,
      blood loss, complications and reduction were recorded and evaluated. The function
      of hip joint were accessed at the final follow-up. RESULTS: The operation time
      ranged from 190 to 290 min with an average of 240 min. The mean blood loss was 1
      800 ml (ranged, 1 300 to 3 000 ml). One case had superficial infection and healed
      after 3 weeks. According to Matta reduction criteria, 8 cases obtained anatomical
      reduction, 4 cases got satisfied results and 1 cases got unsatisfied results.
      Eleven cases were followed up with an average of (24.0 +/- 8.0) months, and 2
      cases were lost to follow-up. According to revised Mede d'Aubingne and Postel
      evaluation system, 7 cases got excellent results, 2 good, 1 moderate and 1 poor.
      CONCLUSION: Posteroproximal-posteroanterior sequential reduction and internal
      fixation for the treatment of type C1 (AO/ASIF) acetabular fracture can achieve
      satisfied surgical proces and operation quality.

PMID- 24015663
TI  - [The un-healing cause of its management after operation of thoracolumbar
      tuberculosis].
AB  - OBJECTIVE: To analyze the un-healing cause and management after operation of
      thoracolumbar tuberculosis. METHODS: From January 2008 to December 2011, the data
      of 12 patients with postoperative un-healing thoracolumbar tuberculosis were
      retrospectively analyzed. There were 5 males and 7 females, with an average age
      of 51.3 years old (ranged, 42 to 65). All the patients occurred different degree
      of vertebral destruction, abscess-formation, kyphosis and nerve functional injury
      at the first operation. Among them, 11 patients underwent debridement and fusion
      with autogenous iliac bone grafting and internal fixation, 1 patient underwent
      debridement and fusion with autogenous iliac bone grafting. At 2-6 months after
      operation, internal fixation loosening, fusion failure, abscess-ormation, or
      erythrocyte sedimentation rate increasing occurred in the patients. For the
      patients to adjust anti-tuberculosis scheme, 2 patients were treated with
      puncture to multiple abscess combining with rifampicin local injection; 10
      patients were reoperated with debridement and internal fixation adjusting.
      RESULTS: At 1-2.5 years (mean 1.8 years) after follow-up, 9 cases were cured
      finally. Re-admission had 3 cases because of re-occurred erythrocyte
      sedimentation rate increasing and abscess-formation at the 2-4 months after
      operation, whose bacterial culture showed more than 2 kinds of drug fast, and the
      treatment effect was still not ideal after adjusting anti-tuberculosis scheme.
      CONCLUSION: Insufficient anti-tuberculosis and bad nutritional status before
      operation,incomplete debridement and unreasonable fixation style during
      operation, inadequate drainage, irregular anti-tuberculosis and drug fast of
      Bacillus tuberculosis after operation are main reasons leading to un-healing of
      tuberculosis. Therefore, actively improving malnutrition, making individual
      operation plan before operation, ensuring complete debridement, rebuilding spinal
      stability, removing the compression of spinal cord, combining with postoperative
      effective, enough, regular combination chemotherapy are important guarantee to
      cure of spinal tuberculosis.

PMID- 24015664
TI  - [Progress on dynamic neutralization system in treating lumbar degenerative
      diseases].
AB  - Dynamic stabilization technology has increasingly become the hot spot in basic
      and clinical research for treating lumbar degenerative diseases. As one kind of
      dynamic stabilization technology,dynamic neutralization system (Dynesys) keeps
      the spinal motion ability and improve clinical symptoms of patients, moreover, it
      shows a certain advantage in delaying the degeneration of adjacent segments. From
      the available documents,the preliminary biomechanical and clinical results of
      Dynesys were optimistically, it has become another choice in treating the lumbar
      degenerative diseases besides the lumbar fusion, and it primarily applies to the
      treatment of mild to moderate lumbar degenerative disease. However, it lacks a
      mechanism to maintain and restore the lumbar lordosis and patients need active
      stretching to achieve lordosis. What's more, how to extend the service life and
      prevent complications remain to be solved, the long-term effect and the mechanism
      of delaying the adjacent segment degeneration need further investigation. In this
      article, the design principle, biomechanical research, clinical outcome and
      clinical application of Dynesys was reviewed.

PMID- 24015665
TI  - [Surgical treatment for chronic radial head dislocation].
AB  - At present, treatment for chronic radial head dislocation mainly focus on open
      reduction, and conservative treatment is invalid. While the surgical procedure
      generally applies to extend ulnar, short radial, reset radial head. Repair or
      reconstruction of annular ligament is the focus of study. For the dysfunction,
      radial head resection served as the final choice. Early diagnosis is the key to
      the treatment of chronic radial head dislocation. While ulnar or radial osteotomy
      and non-reconstruction of annular ligament is still the main trend of today.

PMID- 24015666
TI  - Small-sided games for young athletes: is game specificity influential?
AB  - This study aimed to quantify and compare the physiological, physical and
      technical demands of a sport-specific and non-sport-specific small-sided game
      (SSG) in young athletes. Ten male soccer players (mean +/- SD: age, 13.0 +/- 0.3
      years, [Formula: see text]O2peak, 54.4 +/- 4.9 ml . kg(-1) . min(-1)) completed 3
      vs. 3 and 6 vs. 6 soccer and "bucketball" SSGs twice. Games lasted for 16 min and
      were performed in a randomised order, at least 48 h apart. Movement patterns and
      heart rate were measured using 4 Hz global positioning systems. Technical skill
      executions were assessed by video analysis and ratings of perceived exertion
      (RPE) using the Borg scale (RPEs, 6-20). Total distance (4.9 +/- 4.1% and 8.3 +/-
      6.6%), distance at 7-12.9 km . h(-1) (14.5 +/- 12.5% and 14.9 +/- 16.1%), total
      possessions (14.7 +/- 18.0% and 12.9 +/- 18.9%) and percentage of successful
      passes (24.1 +/- 11.7% and 30.1 +/- 17.6%) were higher for bucketball compared to
      soccer (3 vs. 3 and 6 vs. 6, respectively). Total distance at 13-17.9 km . h(-1)
      was higher for 6 vs. 6 than 3 vs. 3 bucketball (32.3 +/- 21.2%). There was likely
      substantial difference for %HRpeak (89.5 +/- 3.1 vs. 87.4 +/- 2.8 b . min(-1))
      and time above 90% HRpeak (570 +/- 288 s vs. 361 +/- 288 s) between bucketball
      and soccer (3 vs. 3 and 6 vs. 6, respectively). Young players travelled further
      at higher overall speeds, experienced higher physiological workloads and
      performed more successful technical executions during the non-sport-specific SSG.

PMID- 24015667
TI  - Inhibitors of the arachidonic acid cascade: interfering with multiple pathways.
AB  - Modulators of the arachidonic acid cascade have been in the focus of research for
      treatments of inflammation and pain for several decades. Targeting this complex
      pathway experiences a paradigm change towards the design and development of multi
      target inhibitors, exhibiting improved efficacy and less undesired side effects.
      This minireview summarizes recent developments in the field of designed multi
      target ligands of the arachidonic acid cascade. In addition to the well-known
      dual inhibitors of 5-lipoxygenase and cyclooxygenase-2 such as licofelone, very
      recent developments are discussed. Especially, multi-target inhibitors
      interfering with the cytochrome P450 pathway via inhibition of soluble epoxide
      hydrolase seem to offer a novel opportunity for development of novel anti
      inflammatory drugs. 

PMID- 24015668
TI  - Burden of menstrual symptoms in Japanese women: results from a survey-based
      study.
AB  - . OBJECTIVE: Menstrual symptoms are associated with various health problems in
      women and may also significantly impact their lives. This study aims to assess
      the current burden of menstrual symptoms in Japanese women. METHODS: Two online
      surveys were conducted among women aged 15-49 years, where sampling was designed
      to approximate the age and geographic distribution in Japan. The first survey
      collected data on menstrual symptom severity based on a modified, 35-item,
      Japanese version of the Menstrual Distress Questionnaire (mMDQ), current
      treatments, and impact on work productivity. The second survey collected costs of
      outpatient treatment within the previous 3 months. Additional outcomes of the
      second survey will be presented in a separate paper. RESULTS: In this study,
      19,254 women had menses, with 74% suffering from menstrual symptoms. A total of
      50% reported pain and 19% reported heavy bleeding. Increasing severity of
      menstrual symptoms and self-reported heavy bleeding were related to more
      outpatient visits and greater work productivity loss. Among subjects with heavy
      bleeding, increasing severity of symptoms was related to greater interference
      with daily life. The estimated annual economic burden extrapolated to the
      Japanese female population was 683 billion Japanese Yen (JPY) or ~8.6 billion
      United States Dollars (USD). LIMITATIONS: The study population may be biased due
      to the online survey method. CONCLUSIONS: To the authors' knowledge, this is the
      first large-scale research assessing outcomes by severity categories for all
      menstrual symptoms and women's perception of bleeding. A large proportion of
      women suffer from menstrual symptoms, and symptom severity impacts women's lives.
      Menstrual symptoms lead to significant economic burden, mainly due to work
      productivity loss. However, the majority of women do not visit a gynecologist,
      even when their menstrual symptoms are severe. Thus, increasing public awareness
      on the recently available medical treatments has the potential to improve the
      overall burden of menstrual problems.

PMID- 24015669
TI  - In situ transmission electron microscopy observation of the conversion mechanism
      of Fe2O3/graphene anode during lithiation-delithiation processes.
AB  - Transition metal oxides have attracted tremendous attention as anode materials
      for lithium ion batteries (LIBs) recently. However, their electrochemical
      processes and fundamental mechanisms remain unclear. Here we report the direct
      observation of the dynamic behaviors and the conversion mechanism of
      Fe2O3/graphene in LIBs by in situ transmission electron microscopy (TEM). Upon
      lithiation, the Fe2O3 nanoparticles showed obvious volume expansion and
      morphological changes, and the surfaces of the electrode were covered by a
      nanocrystalline Li2O layer. Single-crystalline Fe2O3 nanoparticles were found to
      transform to multicrystalline nanoparticles consisting of many Fe nanograins
      embedded in Li2O matrix. Surprisingly, the delithiated product was not Fe2O3 but
      FeO, accounting for the irreversible electrochemical process and the large
      capacity fading of the anode material in the first cycle. The charge-discharge
      processes of Fe2O3 in LIBs are different from previously recognized mechanism,
      and are found to be a fully reversible electrochemical phase conversion between
      Fe and FeO nanograins accompanying the formation and disappearance of the Li2O
      layer. The macroscopic electrochemical performance of Fe2O3/graphene was further
      correlated with the microcosmic in situ TEM results. 

PMID- 24015670
TI  - Keto-enol tautomerism and conformational landscape of 1,3-cyclohexanedione from
      its free jet millimeter-wave absorption spectrum.
AB  - The free jet millimeter-wave absorption spectrum of 1,3-cyclohexanedione has been
      investigated in the 59.6-74.4 GHz frequency range, and the rotational spectra of
      two conformational species, the chair-diketo and boat-diketo, and probably one
      excited vibrational state belonging to the chair-diketo form have been assigned.
      Quantum chemical calculations, performed at the B3LYP/6-311++G** and MP2/6
      311++G** levels, were used to characterize the potential energy surface minima.
      The potential energy surface related to the interconversion of the observed
      diketonic species was modeled at the DFT level. 

PMID- 24015672
TI  - Pulsed galvanostatic control of a polymeric membrane ion-selective electrode for
      potentiometric immunoassays.
AB  - Pulsed galvanostatic control of ion fluxes across polymeric membrane ion
      selective electrodes (ISEs) is an emerging field for potentiometric sensing.
      Herein we report a novel potentiometric enzyme immunoassay based on current
      controlled release of an enzyme substrate, which eliminates the addition of
      marker ions in the sample solution. In this method, the carboxylated poly(vinyl
      chloride) matrix at the outer layer of the ISE membrane is employed to attach a
      primary antibody. A sandwich immunoassay with an alkaline phosphatase labeled
      antibody (ALP-Ab) as the reporter is used for the determination of human IgG (as
      a model protein). The large difference between the lipophilicity of the substrate
      ion and that of the product ion allows p-nitrophenyl phosphate to be used as the
      enzyme substrate for potentiometric immunosensors. After the immunoreactions, the
      captured ALP-Ab catalyzes the hydrolysis of the substrate ions released at the
      sample-membrane interface by using the pulsed galvanostatic technique. This
      process can be potentiometrically determined by measuring the open circuit
      potential of the ISE. Under optimal conditions, the potential response of the
      proposed immunosensor is proportional to the concentration of human IgG in the
      range of 50-1000 ng/mL with a detection limit of 30 ng/mL (3sigma). Owing to
      simplicity and independence of sample volume and sample turbidity, the proposed
      potentiometric immunoassay offers a viable alternative to those based on optical
      absorbance. 

PMID- 24015671
TI  - Crystal structure of the TRIM25 B30.2 (PRYSPRY) domain: a key component of
      antiviral signalling.
AB  - TRIM (tripartite motif) proteins primarily function as ubiquitin E3 ligases that
      regulate the innate immune response to infection. TRIM25 [also known as Efp
      (oestrogen-responsive finger protein)] has been implicated in the regulation of
      oestrogen receptor alpha signalling and in the regulation of innate immune
      signalling via RIG-I (retinoic acid-inducible gene-I). RIG-I senses cytosolic
      viral RNA and is subsequently ubiquitinated by TRIM25 at its N-terminal CARDs
      (caspase recruitment domains), leading to type I interferon production. The
      interaction with RIG-I is dependent on the TRIM25 B30.2 domain, a protein
      interaction domain composed of the PRY and SPRY tandem sequence motifs. In the
      present study we describe the 1.8 A crystal structure of the TRIM25 B30.2 domain,
      which exhibits a typical B30.2/SPRY domain fold comprising two N-terminal alpha
      helices, thirteen beta-strands arranged into two beta-sheets and loop regions of
      varying lengths. A comparison with other B30.2/SPRY structures and an analysis of
      the loop regions identified a putative binding pocket, which is likely to be
      involved in binding target proteins. This was supported by mutagenesis and
      functional analyses, which identified two key residues (Asp(488) and Trp(621)) in
      the TRIM25 B30.2 domain as being critical for binding to the RIG-I CARDs.

PMID- 24015673
TI  - Assessment of arterial stiffness in patients with inactive and active Behcet's
      disease.
AB  - OBJECTIVES: Behcet's disease (BD) is a systemic vasculitis involving diverse
      sizes of arteries and veins. The aim of this study was to evaluate the
      relationship between central blood pressures, pulse wave velocity (PWV)
      measurements, and biochemical parameters in patients with inactive and active BD
      and control subjects. METHOD: Ninety-six patients with BD were recruited in this
      study. Each subject was evaluated in active and inactive disease periods. For the
      control group, 54 healthy age- and sex-matched subjects were enrolled. All
      patients completed a standard questionnaire form and various laboratory
      parameters were evaluated. Vascular measurements were performed with a Mobil-O
      Graph 24-h PWA Monitor, an automatic oscillometric device. RESULTS: According to
      the vascular function parameters of patients with active and inactive BD, 24-h,
      day, and night PWV values were higher in patients with active BD than in patients
      with inactive BD (p < 0.05). When we performed a linear regression analysis, 24-h
      PWV was positively correlated with age and duration of BD. Cardiac output (CO)
      values and day central diastolic blood pressure (DBP) were higher in patients
      with BD than in the control group (p < 0.05). CONCLUSIONS: PWV values were higher
      in patients with active BD than in patients with inactive BD. This may be
      explained by more prominent inflammatory changes in the vascular wall in the
      active disease period. Further studies in large populations are required to
      confirm our results.

PMID- 24015674
TI  - Synthesis of amines with pendant boronic esters by borrowing hydrogen catalysis.
AB  - Amine alkylation reactions of alcohols have been performed in the presence of
      boronic ester groups to provide products which are known to have use as molecular
      sensors. The boronic ester moiety could be present in either the alcohol or amine
      starting material and was not compromised in the presence of a ruthenium
      catalyst. 

PMID- 24015675
TI  - Coverage and consistency: bioinformatics aspects of the analysis of multirun
      iTRAQ experiments with wheat leaves.
AB  - The hexaploid genome of bread wheat (Triticum aestivum) is large (17 Gb) and
      repetitive, and this has delayed full sequencing and annotation of the genome,
      which is a prerequisite for effective quantitative proteomics analysis. Aware of
      these constraints we investigated the most effective approaches for shotgun
      proteomic analyses of bread wheat that would support large-scale quantitative
      comparisons using iTRAQ reagents. We used a data set that was generated by two
      dimensional LC-MS of iTRAQ labeled peptides from wheat leaves. The main items
      considered in this study were the choice of sequence database for matching LC-MS
      data, the consistency of identification when multiple LC-MS runs were acquired,
      and the options for downstream functional analysis to generate useful insight.
      For peptide identification we examined the extensive NCBInr plant database, a
      smaller composite cereals database, the Brachypodium distachyon model plant
      genome, the EST-based SuperWheat database, as well as the genome sequence from
      the recently sequenced D-genome progenitor Aegilops tauschii. While the most
      spectra were assigned by using the SuperWheat database, this extremely large
      database could not be readily manipulated for the robust protein grouping that is
      required for large-scale, multirun quantitative experiments. We demonstrated a
      pragmatic alternative of using the composite cereals database for peptide spectra
      matching. The stochastic aspect of protein grouping across LC-MS runs was
      investigated using the smaller composite cereals database where we found that
      attaching the Brachypodium best BLAST hit reduced this problem. Further,
      assigning quantitation to the best Brachypodium locus yielded promising results
      enabling integration with existing downstream data mining and functional analysis
      tools. Our study demonstrated viable approaches for quantitative proteomics
      analysis of bread wheat samples and shows how these approaches could be similarly
      adopted for analysis of other organisms with unsequenced or incompletely
      sequenced genomes. 

PMID- 24015676
TI  - Simultaneous splicing of multiple DNA fragments in one PCR reaction.
AB  - BACKGROUND: Rapid and simultaneous splicing of multiple DNA fragments is
      frequently required in many recombinant DNA projects. However, former overlap
      extension PCRs, the most common methods for splicing DNA fragments, are not
      really simultaneous fusing of multiple DNA fragments. RESULTS: We performed an
      optimized method which allowed simultaneous splicing of multiple DNA fragments in
      one PCR reaction. Shorter outermost primers were prior mixed with other PCR
      components at the same time. A sequential thermo cycling program was adopted for
      overlap extension reaction and amplification of spliced DNA. Annealing
      temperature was relatively higher in the overlap extension reaction stage than in
      the fused DNA amplification. Finally we successfully harvested target PCR
      products deriving from fusion of two to seven DNA fragments after 5-10 cycles for
      overlap extension reaction and then 30 cycles for fused DNA amplification.
      CONCLUSIONS: Our method provides more rapid, economical and handy approach to
      accurately splice multiple DNA fragments. We believe that our simultaneous
      splicing overlap extension PCR can be used to fuse more than seven DNA fragments
      as long as the DNA polymerase can match.

PMID- 24015677
TI  - Strong intermolecular vibrational coupling through cyclic hydrogen-bonded
      structures revealed by ultrafast continuum mid-IR spectroscopy.
AB  - Cyclic hydrogen-bonded structures are common motifs in biological systems,
      providing structural stability and mediating proton transfer for redox reactions.
      The mechanism of proton transfer across hydrogen-bonded interfaces depends on the
      strength of the intermolecular coupling between bridging OH/NH vibrational modes.
      Here we present a novel ultrafast continuum mid-IR spectroscopy experiment to
      study the vibrational dynamics of the 7-azaindole-acetic acid (7AI-Ac)
      heterodimer as a model system for asymmetric cyclic hydrogen-bonded structures.
      In addition to spreading of the excitation across the whole OH band within the
      time resolution of the experiment, excitation of a 300 cm(-1) region of the ~1000
      cm(-1) broad OH stretching mode of the acetic acid monomer leads to a frequency
      shift in the NH stretching mode of the 7AI monomer. This indicates that the NH
      and OH stretching modes located on the two monomers are strongly coupled despite
      being separated by 750 cm(-1). The strong coupling further causes the OH and NH
      bands to decay with a common decay time of ~2.5 ps. This intermolecular coupling
      is mediated through the hydrogen-bonded structure of the 7AI-Ac heterodimer and
      is likely a general property of cyclic hydrogen-bonded structures. Characterizing
      the vibrational dynamics of and the coupling between the high-frequency OH/NH
      modes will be important for understanding proton transfer across such molecular
      interfaces. 

PMID- 24015678
TI  - How to improve neurodevelopmental and quality of life outcomes following early
      surgery for congenital heart disease?

PMID- 24015679
TI  - MultiChIPmixHMM: an R package for ChIP-chip data analysis modeling spatial
      dependencies and multiple replicates.
AB  - BACKGROUND: Chromatin immunoprecipitation coupled with hybridization to a tiling
      array (ChIP-chip) is a cost-effective and routinely used method to identify
      protein-DNA interactions or chromatin/histone modifications. The robust
      identification of ChIP-enriched regions is frequently complicated by noisy
      measurements. This identification can be improved by accounting for dependencies
      between adjacent probes on chromosomes and by modeling of biological replicates.
      RESULTS: MultiChIPmixHMM is a user-friendly R package to analyse ChIP-chip data
      modeling spatial dependencies between directly adjacent probes on a chromosome
      and enabling a simultaneous analysis of replicates. It is based on a linear
      regression mixture model, designed to perform a joint modeling of
      immunoprecipitated and input measurements. CONCLUSION: We show the utility of
      MultiChIPmixHMM by analyzing histone modifications of Arabidopsis thaliana.
      MultiChIPmixHMM is implemented in R and including functions in C, freely
      available from the CRAN web site: http://cran.r-project.org.

PMID- 24015680
TI  - Levels of autistic traits in anorexia nervosa: a comparative psychometric study.
AB  - BACKGROUND: A number of characteristics associated with Autism Spectrum Disorders
      (ASD) are over-represented among patients with Anorexia Nervosa (AN) as well as
      among relatives of these patients. Yet the co-occurrence of autistic traits in AN
      has not been fully explored and no previous study has directly compared self
      reported evaluations of cognitive and socio-affective skills in AN and ASD.
      METHODS: We aimed to determine the degree of overlap between AN and ASD from
      scores on questionnaires classically used to measure ASD impairments. Fifteen AN
      participants, 15 ASD participants and two groups of matched controls completed a
      battery of self-reports measuring: autistic traits (Autism-Spectrum Quotient),
      empathy (Empathy Quotient-short and Interpersonal Reactivity Index), systemizing
      (Systemizing Quotient-short) and alexithymia (Bermond-Vorst Alexithymia
      Questionnaire-B). Univariate comparisons of mean totalled scores were performed
      on each measure (patients vs. controls, and AN vs. ASD), and a Principal
      Component Analysis was used to study subject proximities in a reduced-factor
      space constructed from AQ, BVAQ-B and IRI subscales. RESULTS: These analyses
      revealed similarities in a few cognitive domains (Attention Switching,
      Perspective Taking and Fantasy, lack of emotional introspection) and in some
      nonspecific affective dimensions (depression and feelings of distress), but also
      marked dissimilarities in social skills (the ability to communicate emotions to
      others, empathizing). CONCLUSION: The AN and ASD participants reported similar
      needs for sameness, and similar difficulties understanding their emotions and
      taking the perspective of another, but contrasting abilities to feel concerned in
      interpersonal situations. Our mixed findings encourage further exploration of
      transdiagnostic similarities and associations between these disorders.

PMID- 24015683
TI  - Objectively measured and self-reported nonadherence among Jordanian patients
      receiving hemodialysis.
AB  - This study assessed nonadherence behavior to diet and fluid restrictions and
      examined the association between nonadherence behavior and demographic and
      clinical characteristics among Jordanian adults with end-stage renal disease
      receiving hemodialysis. A descriptive, correlational, cross-sectional design was
      used. The patients were interviewed within the first 90 minutes of dialysis
      session using the Dialysis Dietary and Fluid Nonadherence questionnaire (DDFQ).
      Demographic and clinical data were gathered from the patients and the medical
      records. The objective markers of dietary and fluid nonadherence (potassium,
      phosphorus, blood urea nitrogen, and interdialytic weight gain) were followed for
      the last 3 months, and average values were calculated. Diet and fluid
      nonadherence was common among Jordanian hemodialysis patients as 17-80% were
      nonadherent using different measures. Significant strong associations were found
      between the DDFQ subscales, and significant moderate associations between DDFQ
      and objective markers of dietary and fluid nonadherence. Youth, male gender,
      smokers, prolonged dialysis vintage, and less residual renal function were
      associated with nonadherence regardless of the measures used. There was
      substantial consistency between the DDFQ and objective measures of dietary and
      fluid nonadherence among Jordanian adults with end-stage renal disease receiving
      hemodialysis. Future interventional research should incorporate DDFQ and
      objective markers to measure dietary and fluid nonadherence and health-related
      outcomes. 

PMID- 24015684
TI  - Editorial comment to Dorsal onlay (Barbagli technique) versus dorsal inlay (Asopa
      technique) buccal mucosal graft urethroplasty for anterior urethral stricture: a
      prospective randomized study.

PMID- 24015685
TI  - Do importance of religious faith and healthy lifestyle modify the relationships
      between depressive symptoms and four indicators of alcohol consumption? A survey
      of students across seven universities in England, Wales, and Northern Ireland.
AB  - We examined the associations between depressive symptoms and four indicators of
      alcohol consumption (high frequency of drinking, frequency of heavy episodic
      drinking, problem drinking, and possible alcohol dependence). We also explored
      whether personal importance of religious faith as well as healthy lifestyle had
      any modifying roles in these relationships. During 2007-2008, 3,220 students at
      seven UK universities completed a questionnaire containing questions on CAGE,
      frequency alcohol use, heavy episodic drinking, modified Beck-Depression
      Inventory, physical activity and sleep, and importance of religious faith.
      Multivariate logistic regressions were performed separately for four alcohol
      consumption indicators, stratified by gender. Controlling for demographic
      variables, depressive symptoms were positively associated with problem drinking
      and possible alcohol dependence for both genders. Religiosity was negatively
      associated with frequency of drinking and heavy episodic drinking among both
      genders, while healthy lifestyle was not associated with any of the four measures
      of alcohol consumption among both genders. No evidence suggested that either
      religiosity or healthy lifestyle modified the relationships between depressive
      symptoms and any of the four measures of alcohol consumption. This study shows a
      link between hazardous drinking and mental ill health and suggests religiosity as
      a protective factor for high alcohol consumption. Promotion of students' mental
      and spiritual health could have a preventive role in hazardous drinking at
      universities. 

PMID- 24015686
TI  - Alopecia and hypotrichosis as characteristic findings in Woodhouse-Sakati
      syndrome: report of a family with mutation in the C2orf37 gene.
AB  - Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disorder
      characterized by alopecia, hypogonadism, diabetes mellitus, intellectual
      disability, sensorineural deafness, extrapyramidal signs, and low insulinlike
      growth factor 1 levels. Inter- and intrafamilial phenotypic variability have been
      reported. Mutations in the C2orf37 gene cause WSS. The present report describes
      the clinical signs and symptoms of three affected siblings from a consanguineous
      Bedouin family from Kuwait. Direct sequencing of the C2orf37 gene revealed that
      the c.436delC (p.Ala147Hisfs*9) mutation was present in a homozygous state in all
      affected siblings and in a heterozygous state in the parents and a healthy
      sister. Nine C2orf37 mutations causing WSS have been identified. This family
      shared the mutation reported earlier in Saudi families and families of Bedouin
      tribes from Qatar and Israel. No phenotypic or genotypic correlation has been
      observed. Despite the great phenotypic variability of WSS, hypotrichosis has been
      observed in all individuals with WSS reported. This condition has not been
      reported in the dermatologic literature. WSS should be included in the
      differential diagnosis of syndromic congenital hypotrichosis.

PMID- 24015687
TI  - Techniques of electroanatomic mapping and catheter ablation of atrial
      tachyarrhythmias with a recipient to donor atria conduction.

PMID- 24015688
TI  - More than meets the eye: young children's trust in claims that defy their
      perceptions.
AB  - Children and adults often encounter counterintuitive claims that defy their
      perceptions. We examined factors that influence children's acceptance of such
      claims. Children ages 3-6 years were shown familiar objects (e.g., a rock), were
      asked to identify the objects, and were then told that each object was something
      else (e.g., that the rock was soap). For some children, informants explicitly
      stated that the objects were different from what they appeared to be, whereas
      other children received testimony about the objects' identities without any
      reference to the discrepancy between appearance and reality. Children also
      completed standard tasks measuring appearance-reality understanding. When later
      asked about the objects' identities and properties, children who had a firm
      understanding of the appearance-reality distinction and those who heard
      informants mention that distinction were more accepting of the informants'
      counterintuitive claims. Thus, receptivity to counterintuitive claims can reflect
      conceptual growth rather than simple deference or conformity.

PMID- 24015690
TI  - Maternal affection moderates friend influence on schoolwork engagement.
AB  - This study investigated friend influence over adolescent schoolwork engagement in
      160 same-sex friend dyads (94 female dyads and 66 male dyads). Participants were
      approximately 16 years of age at the outset. Each friend described his or her own
      schoolwork engagement, school burnout, and perceptions of maternal affection. The
      results revealed that maternal affection moderated the influence that the higher
      burnout friend exerted over the subsequent schoolwork engagement of the lower
      burnout friend. The schoolwork engagement of the friend reporting higher levels
      of school burnout predicted a decline in the schoolwork engagement of the friend
      reporting lower school burnout, but only if the latter perceived below-average
      maternal affection.

PMID- 24015689
TI  - Genetic and environmental influences on affiliation with deviant peers during
      adolescence and early adulthood.
AB  - Adolescence and early adulthood is a time when peer groups become increasingly
      influential in the lives of young people. Youths exposed to deviant peers risk
      susceptibility to externalizing behaviors and related psychopathology. In
      addition to environmental correlates of deviant peer affiliation, a growing body
      of evidence has suggested that affiliation with deviant peers is heritable. This
      study examined the magnitude of genetic and environmental influences on
      affiliation with deviant peers, changes in the relative importance of these
      factors, and which of these factors contribute to the stability of affiliation
      across this critical developmental period using a longitudinal twin study design
      that assessed same-sex twins (485 monozygotic pairs, 271 dizygotic pairs) at 3
      discrete ages: 15, 18, and 21 years of age. Biometric models revealed that
      genetic influences increased with age. New genetic influences appeared during
      late adolescence, and no new genetic influences emerged by age 21. Environmental
      influences shared by sibling pairs decreased with age, while the proportion of
      nonshared environmental effects unique to each individual remained relatively
      stable over the course of development. Shared environmental influences were
      largely age-overlapping, whereas nonshared environmental influences were largely
      age-specific. In summary, this study found variance in affiliation with deviant
      peers is explained by shared and nonshared environment effects as well as by
      genetic influences (46% by age 21), supporting the role of genetically influenced
      selection factors. The shared environment was almost exclusively responsible for
      the stability in late adolescence, while genetic influences were primarily
      responsible for stability in early adulthood.

PMID- 24015691
TI  - Longitudinal stability of social competence indicators in a Portuguese sample: Q
      sort profiles of social competence, measures of social engagement, and peer
      sociometric acceptance.
AB  - This study examines the temporal stability (over 3 years) of individual
      differences in 3 domains relevant to preschool children's social competence:
      social engagement/motivation, profiles of behavior and personality attributes
      characteristic of socially competent young children, and peer acceptance. Each
      domain was measured with multiple indicators. Sociometric status categories
      (Asher & Dodge, 1986) and reciprocated friendships were derived from sociometric
      data. Composites for social competence domains were significantly associated
      across all time points. Within age-periods, social competence domains were
      associated with both sociometric and friendship status categories; however,
      neither sociometric status nor reciprocated friendships were stable over time.
      Nevertheless, analyses examining the social competence antecedents to
      reciprocated friendship at age-4 and age-5 suggested that more socially competent
      children in the prior year were more likely to have a reciprocated friendship in
      the current year. Popular and rejected sociometric status categories were also
      associated with social competence indicators in prior years, but this was most
      clearly seen at age-5.

PMID- 24015693
TI  - Exciting journal changes.

PMID- 24015692
TI  - Comparing simple root phenotyping methods on a core set of rice genotypes.
AB  - Interest in belowground plant growth is increasing, especially in relation to
      arguments that shallow-rooted cultivars are efficient at exploiting soil
      phosphorus while deep-rooted ones will access water at depth. However, methods
      for assessing roots in large numbers of plants are diverse and direct comparisons
      of methods are rare. Three methods for measuring root growth traits were
      evaluated for utility in discriminating rice cultivars: soil-filled rhizotrons,
      hydroponics and soil-filled pots whose bottom was sealed with a non-woven fabric
      (a potential method for assessing root penetration ability). A set of 38 rice
      genotypes including the OryzaSNP set of 20 cultivars, additional parents of
      mapping populations and products of marker-assisted selection for root QTLs were
      assessed. A novel method of image analysis for assessing rooting angles from
      rhizotron photographs was employed. The non-woven fabric was the easiest yet
      least discriminatory method, while the rhizotron was highly discriminatory and
      allowed the most traits to be measured but required more than three times the
      labour of the other methods. The hydroponics was both easy and discriminatory,
      allowed temporal measurements, but is most likely to suffer from artefacts. Image
      analysis of rhizotrons compared favourably to manual methods for discriminating
      between cultivars. Previous observations that cultivars from the indica
      subpopulation have shallower rooting angles than aus or japonica cultivars were
      confirmed in the rhizotrons, and indica and temperate japonicas had lower maximum
      root lengths in rhizotrons and hydroponics. It is concluded that rhizotrons are
      the preferred method for root screening, particularly since root angles can be
      assessed.

PMID- 24015694
TI  - Evaluation of methods to assess reduced body fat in patients with anorexia
      nervosa.
AB  - OBJECTIVE: To evaluate skinfold anthropometry and dual-energy x-ray
      absorptiometry (DXA) to estimate percentage of body fat (%BF) in adolescent
      patients with anorexia nervosa (AN). METHODS: We examined 80 female AN patients
      (age 15.6 +/- 1.4 years) and 31 healthy, normal weight sex- and age-matched
      controls with DXA and skinfold anthropometry to estimate %BF. Reference values
      for %BF of the same participants were obtained from a 4-compartment (4C) model,
      which was based on measurements of total body protein (with in vivo neutron
      activation), total body water (with deuterium dilution), and mineral content
      (with DXA). We compared the different methods to assess %BF with Bland-Altman
      analysis of agreement. RESULTS: In the AN group, average %BF was well predicted
      with DXA and skinfold measurements in combination with the Deurenberg equation
      based on 2 skinfolds (DXA 13.9 +/- 6.2 %BF; skinfold 14.5 +/- 4.3 vs 14.1 +/- 6.8
      %BF by the 4C model). In the control group, average %BF was closely predicted by
      skinfold measurements in combination with the Slaughter formula (26.1 +/- 4.5 vs
      25.2 +/- 5.2 %BF by the 4C model) but was overestimated with DXA (31.3 +/- 5.8
      %BF). When compared with the 4C model, all methods under investigation showed
      considerable limits of agreement when predicting %BF in any given individual.
      CONCLUSIONS: In our group of patients with AN, the Deurenberg skinfold model and
      DXA were similar in performance; however, DXA overestimated %BF in healthy
      subjects.

PMID- 24015695
TI  - Improvements in glucose metabolism and insulin sensitivity with a low
      carbohydrate diet in obese patients with type 2 diabetes.
AB  - OBJECTIVE: The optimal diet for weight loss in type 2 diabetes remains
      controversial. This study examined a low-carbohydrate, high-fat diet with
      detailed physiological assessments of insulin sensitivity, glycemic control, and
      risk factors for cardiovascular disease. METHODS: Fourteen obese patients (body
      mass index [BMI] 40.6 +/- 4.9 kg/m(2)) with type 2 diabetes were recruited for an
      "Atkins"-type low-carbohydrate diet. Measurements were made at 0, 12, and 24
      weeks of weight, insulin sensitivity, HbA1c, lipids, and blood pressure. RESULTS:
      Twelve completers lost a mean of 9.7 +/- 1.8 kg over 24 weeks attributable to a
      major reduction in carbohydrates and resultant reduction in total energy intake.
      Glycemic control significantly improved (HbA1c -1.1 +/- 0.25%) with reductions in
      hypoglycemic medication. Fasting glucose, homeostasis model assessment (HOMA),
      and area under the curve (AUC) glucose (intravenous glucose tolerance test
      [IVGTT]) were significantly reduced by week 12 ( p < 0.05). There were
      nonsignificant improvements in insulin sensitivity (SI) at week 12 ( p = 0.19)
      and week 24 ( p = 0.31). Systolic blood pressure was reduced (mean -10.0 mmHg
      between weeks 0 and 24, p = 0.13). Mean high-density lipoprotein (HDL), low
      density lipoprotein (LDL), and total cholesterol all increased. The ratio of
      total: HDL cholesterol and triglycerides was reduced. CONCLUSION: A low
      carbohydrate diet was well tolerated and achieved weight loss over 24 weeks in
      subjects with diabetes. Glycemic control improved with a reduction in
      requirements for hypoglycemic agents.

PMID- 24015697
TI  - Green tea and vitamin E enhance exercise-induced benefits in body composition,
      glucose homeostasis, and antioxidant status in elderly men and women.
AB  - OBJECTIVE: To investigate the effects of green tea plus vitamin E in addition to
      exercise on body composition and metabolic and antioxidant parameters in healthy
      elderly individuals. DESIGN: Interventional randomized controlled prospective
      trial. METHODS: For 12 weeks, 22 elderly men and women (age: 71.1 +/- 1.2 years;
      body mass index: 28.3 +/- 0.5 kg/m(2) [mean +/- SE]) undertook 30 minutes of
      moderately intense walking 6 d/wk. They were randomly assigned to ingest either
      green tea plus vitamin E (GTVE; 3 cups and 400 IU, respectively; n = 11) or
      placebo (n = 11). Data on anthropometrics, fasting insulin and glucose levels,
      physical fitness, dietary intake, safety parameters, and biomarkers of oxidation
      status were recorded and analyzed at the start and end of the study. RESULTS:
      Though dietary intake was unchanged, improved exercise capacity was followed by a
      significant reduction in body weight and fasting insulin levels in all
      participants. Additional consumption of GTVE resulted in a twofold increase in
      serum vitamin E (from 20.4 to 40.6 MUmol/L, p < 0.001) and a decrease of men's
      and women's waist circumferences (from 100.8 and 95.7 to 96.9 and 85.0 cm, p <
      0.05 and p < 0.01, respectively) and fasting glucose levels (from 5.30 to 4.98
      mmol/L, p < 0.01). Plasma protein carbonyls dropped (from 0.93 to 0.77 nmol/mg
      protein, p < 0.05), whereas erythrocyte catalase activities increased (from 26.7
      to 29.7 U/g hemoglobin, p < 0.05) in the GTVE group only. Oral peroxidase
      activities were increased in both groups. CONCLUSIONS: A daily dose of GTVE in
      healthy elderly men and women may improve exercise-induced benefits in body
      composition and glucose tolerance and may also lower oxidative burden.

PMID- 24015696
TI  - An encapsulated juice powder concentrate improves markers of pulmonary function
      and cardiovascular risk factors in heavy smokers.
AB  - OBJECTIVE: Cigarette smoking is associated with reduced pulmonary function and
      increased risk factors for cardiovascular disease. This randomized placebo
      controlled double-blind study evaluated the effects of two different combinations
      of mixed fruit and vegetable juice powder concentrate (Juice Plus+, NSA,
      Collierville, TN) on heavy smokers. METHODS: At baseline (T 0) and after 3
      months' supplementation (T 1), pulmonary function parameters and cardiovascular
      risk factors-that is, plasma total homocysteine (tHcy) with related B vitamins
      and cysteine (tCys) concentrations-were assessed in 75 apparently healthy smokers
      (aged 49.2 +/- 10.6 years, >20 cigarettes/d, duration >=10 years) randomized into
      3 groups: placebo (P), fruit/vegetable (FV) and fruit/vegetable/berry (FVB).
      RESULTS: T 0: most smokers showed abnormalities in tHcy and tCys concentrations.
      T 1: respiratory function was unchanged in P and slightly, but not significantly,
      improved in FV, whereas FVB showed a significant improvement in forced expiratory
      flow at 25% (FEF25; p < 0.0001 vs P and FV) and significant improvement in CO
      diffusion lung/alveolar volume (DLCO/VA). FV and FVB (50%) showed significant
      reduction in tHcy and tCys compared to T 0 ( p < 0.0001) and P ( p < 0.0001).
      CONCLUSIONS: At T 1, both supplemented groups, but to a greater extent the FVB
      group, showed improvements in some pulmonary parameters, cardiovascular risk
      factors, and folate status. The beneficial effects of Juice Plus+ supplementation
      could potentially help smokers, even if smoking cessation is advisable.

PMID- 24015698
TI  - Acute effect on satiety, resting energy expenditure, respiratory quotient,
      glucagon-like peptide-1, free fatty acids, and glycerol following consumption of
      a combination of bioactive food ingredients in overweight subjects.
AB  - OBJECTIVE: A combination of bioactive food ingredients (capsaicinoids,
      epigallocatechin gallate, piperin, and l-carnitine, CBFI) may promote satiety and
      thermogenesis. The study was conducted in order to assess whether there is any
      effect on satiety, resting energy expenditure (REE), respiratory quotient,
      glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and glycerol release,
      following a standardized mixed meal with or without single consumption of a CBFI.
      DESIGN: An 8-week randomized double-blind placebo-controlled trial. SETTING:
      Dietetic and Metabolic Unit, Azienda di Servizi alla Persona, University of Pavia
      and "Villa delle Querce" Clinical Rehabilitation Institute, Rome, Italy.
      PARTICIPANTS: Thirty-seven overweight adults (body mass index [BMI]: 25-35).
      INTERVENTION: Nineteen overweight subjects were included in the supplemented
      group (14 women, 5 men; age 46.4 +/- 6.4; BMI: 30.5 +/- 3.3) and 18 in the
      placebo group (13 women, 5 men; age 40.8 +/- 11.5; BMI: 30.1 +/- 2.6). Satiety
      was assessed using 100-mm visual analogue scales (VAS) and the area under the
      curve was calculated. RESULTS: All measured parameters increased significantly in
      comparison with baseline in response to meal, both with CBFI and with placebo.
      However, throughout the study day, the supplemented group experienced a
      significantly greater increase than the placebo group in their sensation of
      satiety following acute administration of the supplement. CONCLUSION: CBFI may
      therefore be of great value in the treatment of overweight patients by increasing
      satiety and stimulating thermogenesis.

PMID- 24015699
TI  - Consumer Acceptance and Preference Study (CAPS) on brown and undermilled Indian
      rice varieties in Chennai, India.
AB  - OBJECTIVES: To study consumer acceptance of unmilled brown and undermilled rice
      among urban south Indians. METHODS: Overweight and normal weight adults living in
      slum and nonslum residences in Chennai participated (n = 82). Bapatla (BPT) and
      Uma (red pigmented) rice varieties were chosen. These rice varieties were
      dehusked (unmilled, 0% polish) and further milled to 2.3% and 4.4% polishing
      (undermilled). Thus, 9 rice samples in both raw and parboiled forms were provided
      for consumer tasting over a period of 3 days. A 7-point hedonic scale was used to
      rate consumer preferences. A validated questionnaire was used to collect
      demographic, anthropometric, medical history, physical activity, dietary intake
      data, and willingness of the consumers to switch over to brown rice. RESULTS:
      Consumers reported that the color, appearance, texture, taste, and overall
      quality of the 4.4% polished rice was strongly preferred in both varieties and
      forms. Ratings for 0% polished (brown rice) were substantially lower than those
      of 2.3% polished rice, which were intermediate in ratings between 0% and 4.4%
      polishing. However, most of the consumers (93%) expressed a willingness to
      substitute brown or 2.3% polished rice, if affordable, after the taste tests and
      education on nutritional and health benefits of whole grains. CONCLUSION: Though
      most consumers preferred polished white rice, education regarding health benefits
      may help this population switch to brown or undermilled rice. Cooking quality and
      appearance of the grains were perceived as the most important factors to consider
      when purchasing rice among Chennai urban adults.

PMID- 24015700
TI  - Comparing effects of carbohydrate (CHO) blockers and trivalent chromium on CHO
      induced insulin resistance and elevated blood pressure in rats.
AB  - OBJECTIVE: In Sprague-Dawley rats (SD), we compared two categories of natural
      dietary supplements that influence carbohydrate (CHO) metabolism via different
      basic mechanisms to ameliorate insulin resistance (IR) and elevated blood
      pressure (BP) associated with heavy sugar/starch consumption. Two dietary
      supplements (bean extract and l-arabinose) are often referred to as carb blockers
      (CBs), because they slow the gastrointestinal absorption of CHO. Trivalent
      chromium (CR) falls into a group of so-called insulin sensitizers, because its
      major effect is to enhance peripheral insulin sensitivity. METHOD: We divided 48
      mature male SD into 4 groups of 12. The first group received powdered baseline
      diet alone (Con). The remaining 3 SD groups (groups 2-4) ingested regular rat
      chow containing 20% w/w sucrose and 20% w/w rice starch. The second group
      received only this CHO-enriched chow. To the high-CHO diets of the remaining two
      groups, either CB to slow CHO absorption (CHO + CB) (group 3) or an insulin
      sensitizer, trivalent CR (CHO + CR; group 4), was added. RESULTS: Compared to Con
      group 1, adding high CHO content to the diet of group 2 significantly increased
      circulating glucose levels and systolic BP (SBP). Addition of CB or CR to the
      feed of groups 3 and 4 overcame the perturbations that occurred with high CHO
      challenge in group 2; that is, they lowered circulating glucose concentrations to
      Con levels, enhanced response to exogenous insulin, and overcame the gradual
      elevation of SBP. Compared to group 2, the two treatment groups (3 and 4) also
      showed decreased renin-angiotensin system activity, decreased serum angiotensin
      converting enzyme activity, and enhanced nitric oxide activity. CONCLUSIONS: Our
      data indicate that high doses of CB and CR, despite their different mechanisms of
      action, can completely overcome CHO-induced IR and BP elevations. The data
      further suggest that CB and CR affect only the changes brought on by heavy CHO
      ingestion, because IR and SBP in groups 3 and 4 mirrored Con values (group 1),
      never producing values lower than baseline. Earlier use of CB and CR in the life
      cycle appears more effective in overcoming CHO-induced perturbations than later
      use.

PMID- 24015701
TI  - The effects of soy and whey protein supplementation on acute hormonal reponses to
      resistance exercise in men.
AB  - OBJECTIVE: For many resistance-trained men concerns exist regarding the
      production of estrogen with the consumption of soy protein when training for
      muscle strength and size. Thus, the purpose of this investigation was to examine
      the effects of soy and whey protein supplementation on sex hormones following an
      acute bout of heavy resistance exercise in resistance trained men. METHODS: Ten
      resistance-trained men (age 21.7 +/- 2.8 [SD] years; height 175.0 +/- 5.4 cm;
      weight 84.2 +/- 9.1 kg) volunteered to participate in an investigation. Utilizing
      a within subject randomized crossover balanced placebo design, all subjects
      completed 3 experimental treatment conditions supplementing with whey protein
      isolate (WPI), soy protein isolate (SPI), and maltodextrin placebo control for 14
      days with participants ingesting 20 g of their assigned supplement each morning
      at approximately the same time each day. Following supplementation, subjects
      performed an acute heavy resistance exercise test consisting of 6 sets of 10
      repetitions in the squat exercise at 80% of the subject's one repetition maximum.
      RESULTS: This investigation observed lower testosterone responses following
      supplementation with soy protein in addition to a positive blunted cortisol
      response with the use of whey protein at some recovery time points. Although sex
      hormone binding globulin (SHBG) was proposed as a possible mechanism for
      understanding changes in androgen content, SHBG did not differ between
      experimental treatments. Importantly, there were no significant differences
      between groups in changes in estradiol concentrations. CONCLUSION: Our main
      findings demonstrate that 14 days of supplementation with soy protein does appear
      to partially blunt serum testosterone. In addition, whey influences the response
      of cortisol following an acute bout of resistance exercise by blunting its
      increase during recovery. Protein supplementation alters the physiological
      responses to a commonly used exercise modality with some differences due to the
      type of protein utilized.

PMID- 24015702
TI  - Eligibility determination for intravenous thrombolysis based on radiology
      interpretation report of the head CT scan in patients with acute ischemic stroke.
AB  - OBJECTIVE: To evaluate the variability of determining eligibility for intravenous
      thrombolysis (IV t-PA) by a stroke team interpretation of computed tomographic
      (CT) scan of the head versus review of the radiology interpretation (presented in
      final report) in patients with acute ischemic stroke. METHODS: We compiled a
      database of all IV t-PA-treated ischemic stroke patients at our academic
      institution based on the stroke team's CT scan interpretation. The CT scan
      reports of 171 patients were reviewed by an independent board-certified vascular
      neurologist who was blinded to clinical information except that all patients were
      being considered for IV t-PA to determine their eligibility for thrombolysis. The
      reviewer's responses were then compared with the treating team's decision to
      identify discrepancies, and the impact of the discrepant decisions on clinical
      outcome including 24-hour National Institute of Health stroke Scale (NIHSS) score
      and discharge modified Rankin scale (mRS), symptomatic hemorrhage (sICH), and
      asymptomatic hemorrhage (aICH). We compared the outcomes of patients who received
      IV t-PA despite cautionary neuroradiologist interpretation and placebo-treated
      patients from NINDS t-PA study. RESULTS: The independent reviewer decided to
      treat with IV t-PA 123 patients (72%) after reviewing the radiology reports. The
      rate of NIHSS score improvement (52.0% vs. 62.5%, P = .22) was not different
      between patients in whom IV t-PA should or should not have been used based on
      radiology reports. Favorable clinical outcome defined by mRS of 0-2 at discharge
      (50.4% vs. 47.9%, P = .77) and in-hospital mortality (15.6% vs. 12.5%, P = .61)
      were similar between the 2 groups. Favorable outcome (discharge or day 7-10 mRS 0
      2) was significantly higher in patients who received t-PA compared with placebo
      treated patients (48% vs. 28%, P = .006). CONCLUSION: Our study demonstrates that
      administering IV t-PA to patients based on the stroke team's interpretation of
      the CT scan versus review of the radiology interpretation does not lead to
      significant differences in clinical outcome, aICH, or sICH.

PMID- 24015704
TI  - Caring for a child with type 1 diabetes: links between family cohesion, perceived
      impact, and parental adjustment.
AB  - This study analyzed the psychological adjustment of parents of children and
      adolescents with type 1 diabetes (T1D) and examined whether family cohesion and
      parental adjustment were connected through the perceived impact of this condition
      on family functioning, as well as whether these links varied according to the
      child's age. In total, 104 parents of children (8-12 years old) and adolescents
      (13-18 years old) with T1D and 142 parents of healthy children and adolescents
      completed self-report measures of family cohesion, parental stress, quality of
      life (QOL), anxious and depressive symptoms, and perceived impact of chronic
      illness. The results indicated that the parents of children and adolescents with
      T1D were more anxious and perceived less family cohesion than the parents of
      healthy children and adolescents. No significant differences were found on
      depressive symptoms, QOL, and parental stress. The hypothesized moderated
      mediation model showed that parents who perceived their family environments as
      more supportive and caring tended to evaluate the impact of T1D on their families
      less negatively; in turn, this perception was associated with better QOL and less
      parental stress and anxious and depressive symptoms. These associations were
      independent of the children's age. Based on a risk and resistance framework, this
      study highlighted the relevance of the perceived impact of T1D on the family as a
      mechanism explaining the link between cohesion and parental adjustment. Family
      centered interventions that help parents better cope with the demands of T1D and
      help family members be more supportive of each other seem to be particularly
      useful in this context.

PMID- 24015703
TI  - Reorientation of the first signal-anchor sequence during potassium channel
      biogenesis at the Sec61 complex.
AB  - The majority of the polytopic proteins that are synthesized at the ER
      (endoplasmic reticulum) are integrated co-translationally via the Sec61
      translocon, which provides lateral access for their hydrophobic TMs
      (transmembrane regions) to the phospholipid bilayer. A prolonged association
      between TMs of the potassium channel subunit, TASK-1 [TWIK (tandem-pore weak
      inwardly rectifying potassium channel)-related acid-sensitive potassium channel
      1], and the Sec61 complex suggests that the ER translocon co-ordinates the
      folding/assembly of the TMs present in the nascent chain. The N-terminus of both
      TASK-1 and Kcv (potassium channel protein of chlorella virus), another potassium
      channel subunit of viral origin, has access to the N-glycosylation machinery
      located in the ER lumen, indicating that the Sec61 complex can accommodate
      multiple arrangements/orientations of TMs within the nascent chain, both in vitro
      and in vivo. Hence the ER translocon can provide the ribosome-bound nascent chain
      with a dynamic environment in which it can explore a range of different
      conformations en route to its correct transmembrane topology and final native
      structure.

PMID- 24015705
TI  - Similarity of relationship standards, couple communication patterns, and marital
      satisfaction among Chinese couples.
AB  - Prior research has indicated that partners' standards for their couple
      relationships are associated with their levels of marital satisfaction, both in
      terms of similarity between standards and the degree to which partners are able
      to resolve differences in their standards constructively. However, little is
      known about processes through which couples effectively cope with conflicting
      relationship standards. Furthermore, most research on relationship standards has
      been conducted in Western countries, and there is a need for more information
      about the role of this form of cognition in Asian and other cultures. In the
      present study, relationship standards and communication patterns were examined in
      relation to marital satisfaction among 297 community couples in a northern city
      in mainland China. Results indicated that the similarity of relationship
      standards of members of real couples was significantly higher than randomly
      matched male-female pairs. A hypothesized conceptual model predicting marital
      satisfaction from partners' similarity of relationship standards and
      communication patterns was tested using structural equation modeling. Similarity
      of relationship standards can affect couple's marital satisfaction indirectly,
      through perceived communication patterns. The interdependence between husbands'
      and wives' aspects of relationship functioning also are examined and discussed.

PMID- 24015706
TI  - Spouse abuse among United States Air Force personnel who deployed in support of
      Operation Iraqi Freedom/Operation Enduring Freedom.
AB  - The authors examined spouse abuse perpetration among all married U.S. Air Force
      personnel who deployed in support of Operation Iraqi Freedom/Operation Enduring
      Freedom. Using Poisson and conditional Poisson regression, they compared rates of
      spouse abuse perpetration predeployment and postdeployment in the population of
      married U.S. Air Force personnel who had a combat-related deployment between
      October 1, 2001 and October 31, 2008 (N = 156,296). Just over 2% (n = 3,524) of
      deployers perpetrated at least one substantiated incident of spouse physical or
      emotional abuse within the 308,197,653 days at risk for abuse during the study
      period. Male deployers perpetrated spouse abuse at approximately twice the rate
      of female deployers. Regarding changes in rates of spouse abuse perpetration
      postdeployment versus predeployment among all deployers, the authors found no
      differences overall; however, several deployer and incident-related
      characteristics moderated this effect. Rates of emotional abuse, mild abuse, and
      abuse not involving alcohol were significantly lower postdeployment, whereas
      rates of moderate/severe abuse and abuse involving alcohol were significantly
      higher postdeployment. Although the majority of U.S. Air Force deployers did not
      perpetrate any substantiated incidents of spouse abuse, there was variability in
      the impact of deployment on spouse abuse rates before versus after deployment.
      The finding that rates of moderate/severe spouse abuse incidents involving
      alcohol were higher postdeployment suggests a need for focused
      prevention/intervention efforts.

PMID- 24015707
TI  - Common dyadic coping is indirectly related to dietary and exercise adherence via
      patient and partner diabetes efficacy.
AB  - Using cross-sectional data from 117 married couples in which one member is
      diagnosed with type 2 diabetes, the current study sought to explore a possible
      indirect association between common dyadic coping and dietary and exercise
      adherence via the mechanism of patient and spouse reports of diabetes efficacy.
      Results from the structural equation model analysis indicated common dyadic
      coping was associated with higher levels of diabetes efficacy for both patients
      and spouses which, in turn, was then associated with better dietary and exercise
      adherence for the patient. This model proved a better fit to the data than three
      plausible alternative models. The bootstrap test of mediation revealed common
      dyadic coping was indirectly associated with dietary adherence via both patient
      and spouse diabetes efficacy, but spouse diabetes efficacy was the only mechanism
      linking common dyadic coping and exercise adherence. This study highlights the
      importance of exploring the indirect pathways through which general intimate
      relationship functioning might be associated with type 2 diabetes outcomes.

PMID- 24015708
TI  - Parenting self-efficacy predicts perceptions of infant negative temperament
      characteristics, not vice versa.
AB  - Infant temperamental characteristics have been found associated with decreasing
      parenting self-efficacy (PSE) during the first year after birth, which has been
      generally interpreted as a child effect on the parent. To test direction of
      effects, PSE was assessed during the third trimester of pregnancy and twice after
      birth together with perceived infant temperament in a group of first-time
      pregnant women (N = 616). Cross-lagged path analysis showed that PSE, even when
      assessed prior to birth, predicted characteristics of infant negative
      temperament. Infant negative temperamental characteristics were concurrently, but
      not prospectively, associated with decreased PSE. These findings indicate that
      perceptions of infant temperament may partly be shaped by parents' self
      perception, rather than the other way around.

PMID- 24015709
TI  - Harsh, inconsistent parental discipline and romantic relationships: mediating
      processes of behavioral problems and ambivalence.
AB  - According to the Development of Early Adult Romantic Relationships (DEARR) model
      (Bryant, C. M., & Conger, R. D. [2002]. Conger, R. D., Cui, M., Bryant, C. M., &
      Elder, G. H., Jr. [2000] interactional characteristics in the family of origin
      influence early adult romantic relationships by promoting or inhibiting the
      development of interpersonal competencies that contribute to relationship success
      in young adulthood. The present study uses the DEARR model as a general framework
      to help examine the long-term link between parental discipline practices in
      adolescence and young adult's interactions in the early years of marriage or
      cohabitation. Using prospective data from 288 target participants, their
      families, and their romantic partner, beginning when the targets were adolescents
      and continuing up to the fifth year of their marital or cohabiting relationships,
      we found empirical support for the DEARR model. Parental discipline practices in
      adolescence were associated with romantic relationship quality during the early
      years of marriage or cohabitation through processes in late adolescence and young
      adulthood. Specifically, harsh and inconsistent discipline practices were
      associated with greater attitudinal ambivalence toward parents in adolescence.
      Inconsistent discipline was also associated with higher risks of externalizing
      problems during late adolescence years. Externalizing problems and ambivalence
      toward parents predicted poorer relationship quality through aggressive behaviors
      and ambivalence toward a romantic partner during the early years of marriage or
      cohabitation. Implications for practitioners working with couples and families
      are discussed.

PMID- 24015710
TI  - Mycobacterium tuberculosis DNA gyrase ATPase domain structures suggest a
      dissociative mechanism that explains how ATP hydrolysis is coupled to domain
      motion.
AB  - DNA gyrase, a type II topoisomerase, regulates DNA topology by creating a double
      stranded break in one DNA duplex and transporting another DNA duplex [T-DNA
      (transported DNA)] through this break. The ATPase domains dimerize, in the
      presence of ATP, to trap the T-DNA segment. Hydrolysis of only one of the two
      ATPs, and release of the resulting Pi, is rate-limiting in DNA strand passage. A
      long unresolved puzzle is how the non-hydrolysable ATP analogue AMP-PNP
      (adenosine 5'-[beta,gamma-imido]triphosphate) can catalyse one round of DNA
      strand passage without Pi release. In the present paper we discuss two crystal
      structures of the Mycobacterium tuberculosis DNA gyrase ATPase domain: one
      complexed with AMP-PCP (adenosine 5'-[beta,gamma-methylene]triphosphate) was
      unexpectedly monomeric, the other, an AMP-PNP complex, crystallized as a dimer.
      In the AMP-PNP structure, the unprotonated nitrogen (P-N=P imino) accepts
      hydrogen bonds from a well-ordered 'ATP lid', which is known to be required for
      dimerization. The equivalent CH2 group, in AMP-PCP, cannot accept hydrogen bonds,
      leaving the 'ATP lid' region disordered. Further analysis suggested that AMP-PNP
      can be converted from the imino (P-N=P) form into the imido form (P-NH-P) during
      the catalytic cycle. A main-chain NH is proposed to move to either protonate AMP
      P-N=P to AMP-P-NH-P, or to protonate ATP to initiate ATP hydrolysis. This
      suggests a novel dissociative mechanism for ATP hydrolysis that could be
      applicable not only to GHKL phosphotransferases, but also to unrelated ATPases
      and GTPases such as Ras. On the basis of the domain orientation in our AMP-PCP
      structure we propose a mechanochemical scheme to explain how ATP hydrolysis is
      coupled to domain motion.

PMID- 24015711
TI  - Antibodies to N-homocysteinylated albumin and haemoglobin in patients with
      rheumatoid arthritis: a potential new marker of disease severity.
AB  - OBJECTIVES: To investigate whether anti-Nepsilon-homocysteinylated albumin (anti
      N-Hcy-Alb) and haemoglobin (anti-N-Hcy-Hb) antibodies occur in rheumatoid
      arthritis (RA) and whether they are associated with RA activity and/or severity.
      METHOD: Plasma total homocysteine (tHcy) and serum anti-N-Hcy-Alb and -Hb
      antibodies levels were determined in 76 RA patients (12 men and 64 women, median
      age 56 years) and 80 age- and sex-matched controls. RESULTS: RA patients compared
      to healthy controls demonstrated elevated tHcy [median (IQR), 13.20 (3.80) vs.
      9.45 (3.25) MUmol/L; p < 0.000001] and anti-N-Hcy-Alb and -Hb antibodies
      [absorbance at 490 nm, median (IQR), 0.546 (0.085) vs. 0.452 (0.056) and 0.649
      (0.106) vs. 0.532 (0.057), respectively; all p < 0.000001]. In RA patients, RA
      radiological class was a strong independent predictor of tHcy [beta (SE), 0.59
      (0.11); p = 0.000001] and anti-N-Hcy-Alb [0.36 (0.12); p = 0.003] and -Hb [0.49
      (0.11); p = 0.00007] antibodies. The number of swollen joints, but not C-reactive
      protein (CRP), interleukin 6 (IL-6), positive rheumatoid factor (RF), or anti
      cyclic citrullinated peptide (anti-CCP) antibodies, showed independent effects on
      anti-N-Hcy-Alb [beta (SE), 0.36 (0.11); p = 0.001] and -Hb [0.25 (0.11); p =
      0.02] antibodies. Anti-N-Hcy-Hb antibodies, but not those against N-Hcy-Alb, were
      positively correlated with RA functional class and RA duration. No effect of any
      medications on tHcy or anti-N-Hcy-protein antibodies was observed. CONCLUSIONS:
      This study is the first to show that RA is characterized by enhanced autoimmune
      response to Nepsilon-homocysteinylated proteins detectable in circulating blood,
      which is related to some clinical measures of RA severity.

PMID- 24015712
TI  - Outcomes of lobectomy in patients with severely compromised lung function
      (predicted postoperative diffusing capacity of the lung for carbon monoxide % <=
      40%).
AB  - RATIONALE: Patients defined as high operative risk by pulmonary function tests
      are often denied lobectomy or offered potentially less curative options,
      including sublobar resection or stereotactic body radiation therapy. OBJECTIVES:
      The aim of this study was to determine the outcomes of lobectomy in a group of
      patients deemed high risk based on predicted postoperative diffusing capacity of
      carbon monoxide (DlCO) less than or equal to 40%. METHODS: This is a
      retrospective review of a prospectively collected database of patients who
      underwent lobectomy with a predicted postoperative DlCO% less than or equal to
      40%. Survival was calculated using the Kaplan-Meier method, and multivariate
      predictors were determined using regression analysis. MEASUREMENTS AND MAIN
      RESULTS: Lobectomy was performed in 50 patients with a predicted DlCO less than
      or equal to 40% (median predicted postoperative DlCO%, 35%). The median age was
      71 years, 68% (n = 34) were women, and 84% (n = 42) had an Eastern Cooperative
      Oncology Group performance status of 0. Eight patients had both predicted
      postoperative FEV1% or predicted postoperative DlCO% less than or equal to 40%.
      Thoracoscopic lobectomy was performed in 36% (n = 18) and reoperations in 6% (n =
      3). There was no operative mortality. Seventy percent (n = 35) of patients had no
      complications, with a median length of stay of 5 days. The most frequent
      complications were pulmonary (14% [n = 7]) and cardiovascular (12% [n = 6]). Four
      patients (8%) were discharged on home oxygen, and four (8%) required
      rehabilitation post discharge. Multivariable analyses evaluating the effects of
      age, sex, comorbidities, smoking status, and operative approach on all-cause
      morbidity, postoperative home oxygen use, and a composite of the two were
      performed. Diabetes was found to be a predictor of the composite of all-cause
      morbidity and postoperative home oxygen use. Overall 5-year survival for the
      entire cohort was 69% (95% confidence interval, 52-87%). CONCLUSIONS: Lobectomy
      can be safely performed in select patients considered to be high risk for
      resection by pulmonary function tests. Additional criteria are needed to assess
      risk.

PMID- 24015713
TI  - The influence of physical and cognitive factors on reactive agility performance
      in men basketball players.
AB  - This study explored the influence of physical and cognitive measures on reactive
      agility performance in basketball players. Twelve men basketball players
      performed multiple sprint, Change of Direction Speed Test, and Reactive Agility
      Test trials. Pearson's correlation analyses were used to determine relationships
      between the predictor variables (stature, mass, body composition, 5-m, 10-m and
      20-m sprint times, peak speed, closed-skill agility time, response time and
      decision-making time) and reactive agility time (response variable). Simple and
      stepwise regression analyses determined the individual influence of each
      predictor variable and the best predictor model for reactive agility time.
      Morphological (r = -0.45 to 0.19), sprint (r = -0.40 to 0.41) and change-of
      direction speed measures (r = 0.43) had small to moderate correlations with
      reactive agility time. Response time (r = 0.76, P = 0.004) and decision-making
      time (r = 0.58, P = 0.049) had large to very large relationships with reactive
      agility time. Response time was identified as the sole predictor variable for
      reactive agility time in the stepwise model (R(2) = 0.58, P = 0.004). In
      conclusion, cognitive measures had the greatest influence on reactive agility
      performance in men basketball players. These findings suggest reaction and
      decision-making drills should be incorporated in basketball training programmes.

PMID- 24015714
TI  - Risk factors for cardiovascular disease: a cautionary tale of diet-microbiome
      interactions.

PMID- 24015715
TI  - Cereal processing influences postprandial glucose metabolism as well as the GI
      effect.
AB  - OBJECTIVE: Technological processes may influence the release of glucose in
      starch. The aim of this study was to compare the metabolic response and the
      kinetics of appearance of exogenous glucose from 2 cereal products consumed at
      breakfast. METHODS: Twenty-five healthy men were submitted to a randomized, open,
      crossover study that was divided into 2 parts: 12 of the 25 subjects were
      included in the "isotope part," and the 13 other subjects were included in the
      "glycemic part." On test days, subjects received biscuits (low glycemic index
      [GI], high slowly available glucose [SAG]) or extruded cereals (medium GI, low
      SAG) as part of a breakfast similar in terms of caloric and macronutrient
      content. The postprandial phase lasted 270 minutes. RESULTS: The rate of
      appearance (RaE) of exogenous glucose was significantly lower after consumption
      of biscuits in the first part of the morning (90-150 minutes) than after
      consumption of extruded cereals (p <= 0.05). Conversely, at 210 minutes, it was
      significantly higher with biscuits (p <= 0.01). For the first 2 hours, plasma
      glucose and insulin were significantly lower after biscuits during the glycemic
      part. C-peptide plasma concentrations were significantly lower at 90, 120, and
      150 minutes after ingestion of the biscuits (p <= 0.05). CONCLUSION: The
      consumption of biscuits with a high content of slowly digestible starch reduces
      the appearance rate of glucose in the first part of the morning and prolongs this
      release in the late phase of the morning (210 minutes). Our results also
      emphasize that modulation of glucose availability at breakfast is an important
      factor for metabolic control throughout the morning in healthy subjects due to
      the lowering of blood glucose and insulin excursions.

PMID- 24015716
TI  - Simulated adaptations to an adult dietary self-report tool to accommodate
      children: impact on nutrient estimates.
AB  - OBJECTIVE: To simulate the effect of child-friendly (CF) adaptations of the
      National Cancer Institute's Automated Self-Administered 24-Hour Dietary Recall
      (ASA24) on estimates of nutrient intake. METHOD: One hundred twenty children, 8
      13 years old, entered their previous day's intake using the ASA24 and completed
      an interviewer-administered recall using the Nutrition Data System for Research
      (NDSR). Based on a hypothesis that proposed adaptations to the ASA24 will not
      significantly affect mean nutrient estimates, ASA24 data were manipulated
      postadministration to simulate a CF version in which 2 categories of data
      collection were removed: (1) foods not likely to be consumed by children (45%)
      based on previous analyses of national dietary data and (2) food detail questions
      (probes) to which children are unlikely to know the answers (46%), based on our
      experience. RESULTS: Mean estimates of select nutrients between the beta version
      of ASA24 and the simulated CF recall showed no significant differences,
      indicating that the food and probe elimination did not significantly affect
      results. However, a comparison of total sugar and vitamin C assessments between
      the original ASA24, the CF version, and NDSR showed that the daily nutrient
      totals for both nutrients were significantly higher in the self-administered
      methods (both ASA24 and CF version) than in NDSR (interviewer-administered),
      which warrants a review of different methods for obtaining information about
      foods that are sources of these nutrients. CONCLUSION: The simulation of CF
      adaptations showed that it is feasible to implement, thereby reducing CF response
      burden without significantly affecting the results.

PMID- 24015717
TI  - Effects of soy-soluble fiber and flaxseed gum on the glycemic and insulinemic
      responses to glucose solutions and dairy products in healthy adult males.
AB  - OBJECTIVE: Soy-soluble polysaccharides and flaxseed gum are underutilized dietary
      fibers of interest to the food industry. However, because the ability of soluble
      fibers to modulate postprandial glucose and insulin metabolism has been related
      to their viscous effects, the utility of these and other low-viscosity soluble
      fibers remains unproven. The objective of this study was to examine the
      associations between soy-soluble polysaccharides and flaxseed gum concentration,
      product viscosity, and the postprandial glycemic and insulinemic responses in the
      context of glucose solutions as well as fluid and gelled dairy products. METHODS:
      Twelve healthy males participated in a randomized crossover postprandial study in
      which they visited the laboratory following overnight fasts on 11 occasions to
      consume one of 11 study treatments, each consisting of 50 g available
      carbohydrates. The study treatments included a glucose reference (in duplicate),
      glucose solutions containing soy-soluble polysaccharides (6%), flaxseed gum
      (0.7%), or guar gum (0.23%), all matched for an apparent viscosity of 61 mPa.s at
      50 s-1, as well as dairy-based beverages and puddings with 0% or 1% soluble fiber
      added. Blood samples were collected at fasting and up to 2 hours postprandially
      for determination of glucose and insulin concentrations. Area under the curve
      (AUC), peak concentration, and time-to-peak values as well as glycemic index (GI)
      and insulinemic index (II) were calculated. RESULTS: Fiber fortification of a 50
      g glucose solution had no effect on postprandial blood glucose or insulin levels,
      even at a high concentration (i.e., 6% soy-soluble polysaccharides). Glucose AUC
      and GI values for the dairy-based beverage (p < 0.05) and pudding (p < 0.01)
      controls were significantly lower than the glucose reference. Glucose AUC and GI
      values for the soy-soluble polysaccharide-fortified dairy products (p < 0.01) and
      flaxseed gum-fortified dairy products (p < 0.001) were significantly lower than
      the glucose reference. No significant differences were observed between the fiber
      fortified fluid and gelled dairy-based study treatments and no significant
      differences were observed in terms of the insulin AUC, II, and peak insulin
      concentration between any of the dairy products. CONCLUSIONS: All dairy products
      had lower glycemic responses relative to the reference, with no effect of
      beverage versus pudding matrix observed and minimal impact of 1% flaxseed gum or
      soy-soluble polysaccharides. Product apparent viscosity, but not fiber
      concentration, was significantly and inversely correlated with glucose AUC and
      GI.

PMID- 24015718
TI  - Healthy eating index and cardiovascular risk factors among Iranians.
AB  - OBJECTIVE: To determine the associations between Healthy Eating Index (HEI) and
      cardiometabolic risk factors among Iranian population. METHODS: This cross
      sectional study was conducted on 9568 Iranians who participated in Isfahan
      Healthy Heart program (IHHP). Dietary intakes were assessed using a 48-item food
      frequency questionnaire (FFQ). HEI scores were calculated based on the number of
      food groups, different kinds of fat intakes, sodium intake, and dietary diversity
      score in 10 separate components. The assessment of anthropometric and biochemical
      variables was done using standard protocols. RESULTS: Mean +/- SD of the HEI
      score was 39.1 +/- 5.2. Those in the highest quintile of HEI consumed more
      fruits, vegetables, and dairy products and had lower total fat, saturated fatty
      acid, cholesterol, and sodium intakes. HEI scores were inversely associated with
      serum C-reactive protein (CRP) levels in both women and men (beta = -0.07 for
      both men and women; p < 0.001). Women in the highest quintile of HEI had the
      lowest mean values of systolic blood pressure and apolipoprotein B (mean +/- SD =
      112.7 +/- 20.2, 112.6 +/- 20.5, 110.6 +/- 19.5 mmHg; p = 0.001 and mean +/- SD =
      99.3 +/- 26.0, 100.1 +/- 26.6, 97.7 +/- 23.1 (mg/dL); p = 0.04, respectively).
      HEI weakly correlated with various cardiovascular risk factors. CONCLUSIONS: The
      low mean of HEI scores in this sample indicates the need to improve diet quality.
      Higher HEI scores were associated with healthier dietary habits and a weak
      inverse association was found between HEI scores and serum levels of CRP,
      apolipoprotein B, and systolic blood pressure.

PMID- 24015719
TI  - Whey protein supplementation during resistance training augments lean body mass.
AB  - Compared to soy, whey protein is higher in leucine, absorbed quicker and results
      in a more pronounced increase in muscle protein synthesis. OBJECTIVE: To
      determine whether supplementation with whey promotes greater increases in muscle
      mass compared to soy or carbohydrate, we randomized non-resistance-trained men
      and women into groups who consumed daily isocaloric supplements containing
      carbohydrate (carb; n = 22), whey protein (whey; n = 19), or soy protein (soy; n
      = 22). METHODS: All subjects completed a supervised, whole-body periodized
      resistance training program consisting of 96 workouts (~9 months). Body
      composition was determined at baseline and after 3, 6, and 9 months. Plasma amino
      acid responses to resistance exercise followed by supplement ingestion were
      determined at baseline and 9 months. RESULTS: Daily protein intake (including the
      supplement) for carb, whey, and soy was 1.1, 1.4, and 1.4 g.kg body mass-1,
      respectively. Lean body mass gains were significantly (p < 0.05) greater in whey
      (3.3 +/- 1.5 kg) than carb (2.3 +/- 1.7 kg) and soy (1.8 +/- 1.6 kg). Fat mass
      decreased slightly but there were no differences between groups. Fasting
      concentrations of leucine were significantly elevated (20%) and postexercise
      plasma leucine increased more than 2-fold in whey. Fasting leucine concentrations
      were positively correlated with lean body mass responses. CONCLUSIONS: Despite
      consuming similar calories and protein during resistance training, daily
      supplementation with whey was more effective than soy protein or isocaloric
      carbohydrate control treatment conditions in promoting gains in lean body mass.
      These results highlight the importance of protein quality as an important
      determinant of lean body mass responses to resistance training.

PMID- 24015720
TI  - A brief history of the surgery for obesity to the present, with an overview of
      nutritional implications.
AB  - Massive obesity results in serious diseases, which are a major public health
      problem. Surgery is frequently the only means to achieve and sustain significant
      weight loss. This historical overview is aimed at providing knowledge and
      appreciation of this surgery to scientists in other complex areas of nutrition.
      The development of these operations is provided, including their potential
      nutritional sequelae. Because type 2 diabetes frequently improves or resolves
      postoperatively, related operations are being investigated in patients with lower
      weights.

PMID- 24015721
TI  - Long-range segregation phenomena in shape-selected bimetallic nanoparticles:
      chemical state effects.
AB  - A study of the morphological and chemical stability of shape-selected octahedral
      Pt0.5Ni0.5 nanoparticles (NPs) supported on highly oriented pyrolytic graphite
      (HOPG) is presented. Ex situ atomic force microscopy (AFM) and in situ X-ray
      photoelectron spectroscopy (XPS) measurements were used to monitor the mobility
      of Pt0.5Ni0.5 NPs and to study long-range atomic segregation and alloy formation
      phenomena under vacuum, H2, and O2 environments. The chemical state of the NPs
      was found to play a pivotal role in their surface composition after different
      thermal treatments. In particular, for these ex situ synthesized NPs, Ni
      segregation to the NP surface was observed in all environments as long as PtOx
      species were present. In the presence of oxygen, an enhanced Ni surface
      segregation was observed at all temperatures. In contrast, in hydrogen and
      vacuum, the Ni outward segregation occurs only at low temperature (<200-270 
      degrees C), while PtOx species are still present. At higher temperatures, the
      reduction of the Pt oxide species results in Pt diffusion toward the NP surface
      and the formation of a Ni-Pt alloy. A consistent correlation between the NP
      surface composition and its electrocatalytic CO oxidation activity was
      established. 

PMID- 24015722
TI  - Propargyl + O2 reaction in helium droplets: entrance channel barrier or not?
AB  - A combination of liquid He droplet experiments and multireference electronic
      structure calculations is used to probe the potential energy surface for the
      reaction between the propargyl radical and O2. Infrared laser spectroscopy is
      used to probe the outcome of the low temperature, liquid He-mediated reaction.
      Bands in the spectrum are assigned to the acetylenic CH stretch (nu1), the
      symmetric CH2 stretch (nu2), and the antisymmetric CH2 stretch (nu13) of the
      trans-acetylenic propargyl peroxy radical ((*)OO-CH2-C=CH). The observed band
      origins are in excellent agreement with previously reported anharmonic frequency
      computations for this species [Jochnowitz, E. B.; Zhang, X.; Nimlos, M. R.;
      Flowers, B. A.; Stanton, J. F.; Ellison, G. B. J. Phys. Chem. A 2010, 114, 1498].
      The Stark spectrum of the nu1 band provides further evidence that the reaction
      leads only to the trans-acetylenic species. There are no other bands in the CH2
      stretching region that can be attributed to any of the other three propargyl
      peroxy isomers/conformers that are predicted to be minimum energy structures
      (gauche-acetylenic, cis-allenic, and trans-allenic). There is also no evidence
      for the kinetic stabilization of a van der Waals complex between propargyl and
      O2. A combination of multireference and coupled-cluster electronic structure
      calculations is used to probe the potential energy surface in the neighborhood of
      the transition state connecting reactants with the acetylenic adduct. The
      multireference based evaluation of the doublet-quartet splitting added to the
      coupled-cluster calculated quartet state energies yields what are likely the most
      accurate predictions for the doublet potential curve. This calculation suggests
      that there is no saddle point for the addition process, in agreement with the
      experimental observations. Other calculations suggest the possible presence of a
      small submerged barrier.

PMID- 24015723
TI  - A concise construction of polycyclic quinolines via annulation of omega-cyano-1
      alkynes with diaryliodonium salts.
AB  - A concise construction of polycyclic quinolines via intramolecular [2 + 2 + 2]
      annulation of omega-cyano-1-alkynes with diaryliodonium salts was realized. The
      process produced polycyclic quinolines in high yields with readily available
      staring materials and was tolerated with halogen substituents. 

PMID- 24015724
TI  - Surface chemical modification of poly(dimethylsiloxane) for the enhanced adhesion
      and proliferation of mesenchymal stem cells.
AB  - The surface chemistry of materials has an interactive influence on cell behavior.
      The optimal adhesion of mammalian cells is critical in determining the cell
      viability and proliferation on substrate surfaces. Because of the inherent high
      hydrophobicity of a poly(dimethylsiloxane) (PDMS) surface, cell culture on these
      surfaces is unfavorable, causing cells to eventually dislodge from the surface.
      Although physically adsorbed matrix proteins can promote initial cell adhesion,
      this effect is usually short-lived. Here, (3-aminopropyl)triethoxy silane (APTES)
      and cross-linker glutaraldehyde (GA) chemistry was employed to immobilize either
      fibronectin (FN) or collagen type 1 (C1) on PDMS. The efficiency of these
      surfaces to support the adhesion and viability of mesenchymal stem cells (MSCs)
      was analyzed. The hydrophobicity of the native PDMS decreased significantly with
      the mentioned surface functionalization. The adhesion of MSCs was mostly
      favorable on chemically modified PDMS surfaces with APTES + GA + protein.
      Additionally, the spreading area of MSCs was significantly higher on APTES + GA +
      C1 surfaces than on other unmodified/modified PDMS surfaces with C1 adsorption.
      However, there were no significant differences in the MSC spreading area on the
      unmodified/modified PDMS surfaces with FN adsorption. Furthermore, there was a
      significant increase in cell proliferation on the PDMS surface with APTES + GA +
      protein functionalization as compared to the PDMS surface with protein adsorption
      only. Therefore, the covalent surface chemical modification of PDMS with APTES +
      GA + protein could offer a more biocompatible platform for the enhanced adhesion
      and proliferation of MSCs. Similar strategies can be applied for other substrates
      and cell lines by appropriate combinations of self-assembly monolayers (SAMs) and
      extracellular matrix proteins. 

PMID- 24015726
TI  - From tolerance to acute metabolic deregulation: contribution of proteomics to dig
      into the molecular response of alder species under a polymetallic exposure.
AB  - Alnus spp. are actinorhizal trees commonly found in wet habitats and able to grow
      effectively in soil slightly contaminated with metal trace- elements. Two clones
      belonging to two Alnus species, namely, A. incana and A. glutinosa, were grown in
      hydroponics and exposed for 9 weeks to a Cd + Ni + Zn polymetallic constraint.
      Although responding by a similar decrease in total biomass production, the
      proteomic analysis associated with the study of various biochemical parameters
      including carbohydrate and mineral analyses revealed that the two clones have a
      distinct stress-responsive behavior. All parameters indicated that the roots, the
      organ in direct contact with the media, are more affected than the leaves. In
      fact, in A. glutinosa the response was almost completely confined to the roots,
      whereas many proteins change significantly in the roots and in the leaves of the
      treated A. incana. In both clones, the changes affected a broad range of
      metabolic processes such as redox regulation and energy metabolism and induced
      the production of pathogenesis-related proteins. In particular, changes in the
      accumulation of bacterial proteins that were not identified as coming from the
      known symbionts of Alnus were reported. Further investigation should be performed
      to identify their origin and exact role in the plant response to the polymetallic
      exposure tested here. 

PMID- 24015725
TI  - Quantifying transient 3D dynamical phenomena of single mRNA particles in live
      yeast cell measurements.
AB  - Single-particle tracking (SPT) has been extensively used to obtain information
      about diffusion and directed motion in a wide range of biological applications.
      Recently, new methods have appeared for obtaining precise (10s of nm) spatial
      information in three dimensions (3D) with high temporal resolution (measurements
      obtained every 4 ms), which promise to more accurately sense the true dynamical
      behavior in the natural 3D cellular environment. Despite the quantitative 3D
      tracking information, the range of mathematical methods for extracting
      information about the underlying system has been limited mostly to mean-squared
      displacement analysis and other techniques not accounting for complex 3D kinetic
      interactions. There is a great need for new analysis tools aiming to more fully
      extract the biological information content from in vivo SPT measurements. High
      resolution SPT experimental data has enormous potential to objectively scrutinize
      various proposed mechanistic schemes arising from theoretical biophysics and cell
      biology. At the same time, methods for rigorously checking the statistical
      consistency of both model assumptions and estimated parameters against observed
      experimental data (i.e., goodness-of-fit tests) have not received great
      attention. We demonstrate methods enabling (1) estimation of the parameters of 3D
      stochastic differential equation (SDE) models of the underlying dynamics given
      only one trajectory; and (2) construction of hypothesis tests checking the
      consistency of the fitted model with the observed trajectory so that extracted
      parameters are not overinterpreted (the tools are applicable to linear or
      nonlinear SDEs calibrated from nonstationary time series data). The approach is
      demonstrated on high-resolution 3D trajectories of single ARG3 mRNA particles in
      yeast cells in order to show the power of the methods in detecting signatures of
      transient directed transport. The methods presented are generally relevant to a
      wide variety of 2D and 3D SPT tracking applications. 

PMID- 24015727
TI  - Subchronic and reproductive/developmental (screening level) toxicity of
      complexation products of iron trichloride and sodium tartrate (FemTA).
AB  - A complexation/reaction product, termed FemTA, of sodium tartrate [D(-)- and L(+)
      tartaric acid and mesotartaric acid], sodium hydroxide, and iron trichloride may
      have use as an anticaking agent in salt preparations. FemTA is composed of about
      4% sodium tartrate, approximately 10% mesotartaric acid, approximately 7%
      chloride, approximately 4% iron, approximately 7% sodium, approximately 0.3%
      sodium oxalate, and approximately 65% water. FemTA was tested in a 90-d oral
      toxicity study, which included a screening level reproductive/developmental
      toxicity phase, in Harlan Wistar rats. FemTA was administered by oral gavage at
      500, 1000, and 2000 mg/kg body weight/d prior to and during mating, or about 20,
      40, or 80 mg of iron/kg body weight/d, such that males received 90/91 d of
      treatment and females 104 to 109 d. Treatment was associated with inflammatory
      lesions of the lower GI tract at the mid- and high-dose levels, increased liver
      and kidney weights, increased serum bile acids and blood urea nitrogen, decreased
      chloride, and changes to hematological parameters consistent with inflammation.
      The effects were considered the result of iron overload. There were no effects on
      reproductive/developmental toxicity parameters. The no-observed-adverse-effect
      level (NOAEL), based on gastrointestinal tract effects was 500 mg/kg body
      weight/d. The NOAEL for reproductive/developmental toxicity was 2000 mg/kg body
      weight/d, the highest dose tested. 

PMID- 24015728
TI  - Angiographic perfusion imaging: real-time assessment of endovascular treatment
      for cerebral vasospasm.
AB  - BACKGROUND AND PURPOSE: Cerebral perfusion analysis is useful in the diagnosis
      and treatment of cerebral vasospasm. A new modality of real-time cerebral
      perfusion imaging and analysis has been developed using standard 2-dimensional
      angiography. We report our initial experience with this technique to assess
      response to therapy during endovascular vasospasm procedures. METHODS: Colorized
      angiographic perfusion maps were obtained immediately before and after
      endovascular vasospasm treatment. Semiquantitative perfusion parameters (cerebral
      blood flow, cerebral blood volume, mean transit time, and time to peak) were
      calculated from time-density curves obtained from intraarterial contrast
      injection. The effects of intraarterial vasospasm therapy were assessed. RESULTS:
      Eight vascular territories in 4 patients with vasospasm underwent interventional
      angiography and angiographic perfusion analysis. Pretreatment perfusion maps
      demonstrated variable perfusion deficits in specific vascular territories. After
      endovascular treatment in 6 vessels, improvement was seen to varying degrees in
      both angiographic appearance and perfusion parameters. Clinical improvement and
      reduction in transcranial Doppler velocity was also observed. CONCLUSIONS: Real
      time angiographic perfusion imaging is feasible during endovascular procedures
      for vasospasm. Perfusion analysis may aid in assessment of efficacy of the
      intervention. Comparison with traditional perfusion imaging is needed to validate
      this technique.

PMID- 24015730
TI  - Learning together to work together.

PMID- 24015729
TI  - Morphology of far-field electrograms and antitachycardia pacing effectiveness
      among fast ventricular tachycardias occurring in ICD patients: a multicenter
      study.
AB  - INTRODUCTION: Fast ventricular tachycardias (FVT) are less likely to be
      terminated by antitachycardia pacing (ATP). No information is available regarding
      the ability of far-field electrogram (Ff-EG) morphology (Ff-EGm) in predicting
      the result of the subsequent ATP. Our objective is to determine the relationship
      between Ff-EGm and ATP efficacy. METHODS AND RESULTS: In this multicenter study
      we analyzed 289 FVT (cycle length [CL]: 250-320 milliseconds) occurring
      consecutively in 52 ICD patients with Medtronic devices (LVEF: 37 +/- 6; pacing
      site: right ventricular apex). FVT programming was standardized, including a
      single ATP burst as initial therapy. The configuration of Ff-EG was HVA versus
      HVB. FVTs were classified in QFVT or non-QFVT according to the presence or
      absence of a negative initial deflection in the Ff-EG. The mean CL was 291 +/- 24
      milliseconds. We observed 4 Ff-EGm: QS (n = 14, 5%), QR (n = 158, 55%), R (n =
      93, 32%), and RS (n = 24, 8%). The ATP effectiveness was 80% (86% in QS, 85% in
      QR, 74% in R, 62% in RS). The frequency of successful ATP was higher in QFVT: 86
      versus 71% (P = 0.002). By logistic regression analysis, a QFVT pattern (OR =
      2.3; P = 0.015) remained as an independent predictor of effective ATP. ATP was
      safer in QFVTs, the frequencies of shock (14% vs 29%; P = 0.002), acceleration
      (5.1 vs 12.3%; P = 0.02), and syncope (4.6 vs 12.3%; P = 0.01) being lower.
      CONCLUSIONS: Since ATP is less effective in non-QFVTs, they are less well
      tolerated. Therefore, the substrate of non-QFVTs may need a specific treatment.

PMID- 24015731
TI  - Learning styles in vertically integrated teaching.
AB  - BACKGROUND: With vertical integration, registrars and medical students attend the
      same educational workshops. It is not known whether these learners have similar
      or different learning styles related to their level of education within the
      medical training schema. This study aims to collect information about learning
      styles with a view to changing teaching strategies. If a significant difference
      is demonstrated this will impact on required approaches to teaching. METHODS: The
      VARK learning inventory questionnaire was administered to 36 general practice
      registrars and 20 medical students. The learning styles were compared as
      individuals and then related to their level of education within the medical
      training schema. RESULTS: Students had a greater preference for multimodal
      learning compared with registrars (62.5 per cent versus 33.3 per cent,
      respectively). More than half of the registrars preferred uni or bimodal learning
      modalities, compared with one-third of the medical students. DISCUSSION: The
      present workshop format based on visual and aural material will not match the
      learning needs of most learners. This small study has shown that the majority of
      medical students and registrars could have their learning preferences better met
      by the addition of written material to the workshop series. Surprisingly, a
      significantly larger number of medical students than registrars appeared to be
      broadly multimodal in their learning style, and this warrants further research.

PMID- 24015732
TI  - Peer review: a tool to enhance clinical teaching.
AB  - BACKGROUND: The system used by academic health centres to evaluate teaching must
      be valued by the large number of faculty staff that teach in clinical settings.
      Peer review can be used to evaluate and enhance clinical teaching. The objective
      of this study was to determine the perceptions of clinical faculty about the
      effects of participating in peer review. METHODS: Faculty members were observed
      teaching in a clinical setting by trained peer observers. Feedback was provided
      using a checklist of behaviours and descriptive comments. Afterwards, semi
      structured interviews were conducted to assess the faculty member's perception
      about the process. Notes from the interviews were analysed using a grounded
      theory approach. The study was approved by the institutional review boards of all
      the institutions involved. RESULTS: Three themes emerged from the interviews with
      faculty members: (1) they found the process to be valuable - they received
      information that affirmed "good" teaching behaviours, and were prompted to be
      more focused on their teaching; (2) they were motivated to enhance their teaching
      by being more deliberate, interactive and learner-centred; and (3) they were
      inspired to explore other opportunities to improve their teaching skills.
      DISCUSSION: Peer review is a process that promotes the open discussion and
      exchange of ideas. This conversation advances clinical teaching skills and allows
      high-quality teaching behaviours to be strengthened.

PMID- 24015733
TI  - A model for peer-assisted learning in paediatrics.
AB  - BACKGROUND: Previous studies have shown peer-assisted learning (PAL) to be an
      effective method of teaching, with benefits to students and tutors; however, the
      effect of PAL in paediatrics has not been evaluated in the literature. This study
      aimed to evaluate a student-led paediatrics revision course for students
      preparing for examinations in medical specialties. METHODS: Students in their
      specialties year were invited to undergo a 1-day revision course consisting of a
      lecture and small group teaching, with a supplemental revision booklet. Tutors
      were recruited from the final-year cohort to facilitate the teaching.
      Questionnaires containing Likert-scale questions (1, strongly disagree; 5,
      strongly agree) were distributed before and after the course to assess its
      effectiveness. RESULTS: In all, 62 per cent (87/140) of students who attended the
      course responded to the study. Students felt significantly more prepared for
      their exam after the course (mean 3.47 post-course versus 2.16 pre-course), and
      significantly more prepared to manage children in clinical practice (mean 3.49
      post-course versus 2.53 pre-course). Students rated the course as good (4.35/5),
      with the small group sessions deemed to be the most useful aspect. Tutors agreed
      that participating had improved their teaching in general (4.0/5), their
      confidence (4.1/5), their clinical knowledge (3.6/5) and their oral presentation
      skills (3.8/5). DISCUSSION: The results demonstrate an effective model for
      students and tutors in building vital skills in paediatrics and exam preparation.
      This reinforces the holistic positive attributes attainable from peer-assisted
      learning, and such schemes should be incorporated into undergraduate medical
      curricula for paediatrics to increase student confidence and potentially increase
      recruitment to paediatrics.

PMID- 24015734
TI  - Peer-supported learning during 'Health Mela'.
AB  - BACKGROUND: The Lancashire Gujarat Health Users Forum has organised several
      successful 'Health Mela' events in Preston, where medical students actively
      volunteered in health-promotion activities. The participating students enjoyed
      these events, but we were keen to assess whether students derived any benefit
      from it in developing their clinical skills. METHODS: A focus group of 12 medical
      students with varied experience was set up following one such event and a semi
      structured interview was conducted. Their experiences were analysed qualitatively
      and grouped into various themes. RESULTS: The students found that the 'Health
      Mela' was very useful to increase their clinical skills and communication skills.
      It also improved their understanding of preventative medicine, which is not well
      covered in their curriculum. In addition, these events developed teamworking and
      leadership skills. Students were also very pleased because they could use their
      personal skills creatively in the planning and smooth running of the 'Health
      Mela'. DISCUSSION: We believe that medical students should be encouraged to form
      groups to engage in health-promotional activities in the community. This will no
      doubt be beneficial to the community, but in addition will also improve the
      students' knowledge and skills, which will help them to be successful doctors in
      the future.

PMID- 24015735
TI  - Using Gagne's theory to teach procedural skills.
AB  - BACKGROUND: Many key medical procedures are performed every day in clinical
      practice to yield important diagnostic information and to help determine the
      disease response to intensive treatments. Training clinicians to perform
      procedures competently and confidently thus carries considerable weight, helping
      to assure patient safety, the obtainment of adequate samples and minimising
      patient discomfort. This article considers how Robert Gagne's instructional
      design model may be effectively used to design lesson plans and teach procedural
      skills in small group settings. CONTEXT: Gagne's model is based upon the
      information-processing model of mental events that occur when adults are
      presented with various stimuli. It highlights nine specific instructional events,
      which correlate with crucial conditions of learning, and are arranged to
      maximally enhance the learning process, improve session flow and, ultimately,
      ensure lesson objectives are comprehensively addressed. INNOVATION: This article
      uses the nine points described by Gagne to outline a comprehensive lesson guide
      for teaching psychomotor skills, using a bone-marrow aspirate procedure as an
      example. Each of Gagne's instructional events is considered with specific
      activities for each, and with the variety of activities delineated to meet
      diverse learning styles. IMPLICATIONS: Gagne's instructional events can produce
      an effective and comprehensive lesson plan for teaching procedural skills,
      preparing learners with various preferred learning styles to perform psychomotor
      skills competently in clinical practice. This lesson plan can be of use for both
      teachers and students across clinical specialties, encouragingly outlining how
      Gagne's systematic and widely referenced theory can be creatively and practically
      used.

PMID- 24015736
TI  - Teaching clinical reasoning to medical students.
AB  - BACKGROUND: Keele Medical School's new curriculum includes a 5-week course to
      extend medical students' consultation skills beyond those historically required
      for competent inductive diagnosis. CONTEXT: Clinical reasoning is a core skill
      for the practice of medicine, and is known to have implications for patient
      safety, yet historically it has not been explicitly taught. Rather, it has been
      assumed that these skills will be learned by accumulating a body of knowledge and
      by observing expert clinicians. This course aims to assist students to develop
      their own clinical reasoning skills and promote their greater understanding of,
      and potential to benefit from, the clinical reasoning skills of others. The
      course takes place in the fourth or penultimate year, and is integrated with
      students' clinical placements, giving them opportunities to practise and quickly
      embed their learning. INNOVATION: This course emphasises that clinical reasoning
      extends beyond initial diagnosis into all other aspects of clinical practice,
      particularly clinical management. It offers students a variety of challenging and
      interesting opportunities to engage with clinical reasoning across a wide range
      of clinical practice. It addresses bias through metacognition and increased self
      awareness, considers some of the complexities of prescribing and non
      pharmacological interventions, and promotes pragmatic evidence-based practice,
      information management within the consultation and the maximising of patient
      adherence. This article describes clinical reasoning-based classroom and
      community teaching. IMPLICATIONS: Early evaluation suggests that students value
      the course and benefit from it.

PMID- 24015737
TI  - Developing teachers of clinical reasoning.
AB  - BACKGROUND: Front-line teachers seek guidance and tools to instruct and remediate
      clinical reasoning, but effective professional development methods to accomplish
      these goals have not been reported. METHODS: A 2-hour workshop was developed to
      empower front-line clinician educators to teach and remediate clinical reasoning
      by understanding the cognitive steps in the clinical reasoning process which can
      be leveraged in clinical settings. The workshop has been given 19 times over 6
      years and uses interactive didactic presentations, facilitated discussion and
      dyad exercises, followed by small group analysis of trainee cases, where the
      diagnosis and remediation of clinical reasoning issues are practised. RESULTS:
      The quality and organisation of the session and the participants' intentions to
      change their teaching practice were rated higher than faculty development
      seminars in the same academic years. Participants cited the four-step model,
      technology analogies and the opportunity to analyse cases with peers as highly
      effective elements of the workshop. DISCUSSION: Similarly structured faculty
      development seminars may help bring insights from clinical reasoning theory to
      bedside and classroom instruction.

PMID- 24015738
TI  - Pro forma: impact on communication skills?
AB  - BACKGROUND: A doctor performs 160 000-300 000 interviews during a lifetime
      career, thus making the medical interview the most common procedure in clinical
      medicine. It is reported that 60-80 per cent of diagnosis is based on history
      taking, yet there is little published data advising on the best method for
      medical students to initially attain and further refine these core skills during
      their medical degree. METHODS: Medical students interviewed two patients: using
      an open interview first, based on the Calgary-Cambridge approach, and then using
      a structured pro forma. The students' medical data were assessed by a senior
      lecturer, and their communication skills were assessed by a behavioural scientist
      and by the patients. RESULTS: An exact Wilcoxon paired signed rank test was
      conducted to determine whether there was a difference between the open interview
      and pro forma methods for history taking and communication skills. The test
      yielded p-values of 0.0017 and 0.069, respectively, with the pro forma method
      providing a statistically significantly higher history-taking score and
      communication score than the open interview method. Subjectively, patients
      reported the pro forma method as being preferable. CONCLUSION: Medical students
      in the early years of training benefit from a structured history-taking pro forma
      to assist them gather an accurate data set without compromising their
      interpersonal and communication skills.

PMID- 24015739
TI  - Implementing student self-video of performance.
AB  - BACKGROUND: Resource and curriculum constraints within contemporary university
      programmes limit opportunities for supervision and feedback of student practice.
      This study investigated the technological challenges, solutions and educational
      rewards in implementing Web-based student self-video of performance as a method
      to foster the development of student self-evaluation. METHODS: Physiotherapy
      students (n = 60) in their final preclinical semester participated in the study.
      All students received guidelines for constructing and uploading self-videos of
      performance to a Web-based learning system. Students completed a reflective task
      on each video submission after receiving online tutor feedback and viewing an
      exemplar peer performance. Students completed a survey of their learning
      experiences and challenges in completing the learning tasks. Technical
      information on submissions was obtained in usage reports from the Web-based
      learning system. RESULTS: Students were successful in recording and uploading
      digital videos of performance for remote tutor review. Students and tutors
      encountered technical problems that could be rectified and potentially avoided
      through activity design. Students reported that the utility of Web-based self
      video for enhancing clinical performance outweighed the additional time and
      effort required in participation. CONCLUSIONS: Web-based student self-video of
      performance, with remote tutor feedback and guided reflection, is a feasible
      method for increasing students' capacity for reflection and self-evaluation.
      Although technical difficulties are inherent in any technology-reliant activity,
      the students' increasing competence with emerging technologies encourage self
      video teaching and learning activities as a resource for facilitating clinical
      skill development.

PMID- 24015741
TI  - How not to do things.

PMID- 24015740
TI  - International medical graduates in transition.
AB  - BACKGROUND: Medical migration is now more frequent, and raises complex issues
      concerning the standards of practice and transitions required for doctors. The
      challenges faced by international medical graduates have been acknowledged
      through the proliferation of orientation programmes designed within hospitals.
      This paper discusses and evaluates a pilot orientation programme for doctors in
      Victoria, Australia, called Transition in Practice. METHODS: Drawing on theories
      of active reflection and situated learning, the programme entailed fortnightly
      meetings for new international medical graduates at a metropolitan hospital in
      Victoria. The programme comprised a series of informal discussion sessions where
      doctors were facilitated to actively reflect on everyday practical challenges in
      their hospital work. Local medical and non-medical staff were invited to each
      session. Data comprised doctors' reflections about new insights gathered at the
      conclusion of each session. RESULTS: Thematic analysis of 55 evaluation cards
      revealed that participants benefited from the programme by learning directly from
      invited staff members' descriptions of their roles and their specific areas of
      practice. Participants gained increased awareness of the differences between
      their past and present work environments, and greater insight into the
      complexities of the local system. Participating doctors became actively involved
      in their own orientation process, generating new topics for future discussions.
      CONCLUSION: This programme successfully integrated experiences and views of both
      international medical graduates and local hospital staff to generate a greater
      understanding of each other and of the workplace. The programme used simple,
      inexpensive methods that tapped into the resources that both international
      medical graduates and local staff bring to the workplace.

PMID- 24015742
TI  - From theory to practice: the reality of failing a student.

PMID- 24015743
TI  - A symbiotic approach to mentoring future academics.

PMID- 24015744
TI  - Interprofessional education.

PMID- 24015750
TI  - Integrating science and medical teaching.

PMID- 24015751
TI  - Calcific mitral stenosis in the hemodialysis patient.
AB  - The dialysis patient is prone to elevations in the calcium phosphorus product and
      hyperparathyroidism, which contributes to valvular and vascular calcification. We
      present the case of a young lady on chronic dialysis that developed mitral
      calcification complicated by severe mitral stenosis, caseous calcification and
      retinal embolization. She subsequently required mitral valve replacement. 

PMID- 24015752
TI  - How direct-to-consumer drug websites convey disease information: analysis of
      stigma-reducing components.
AB  - Given the growing trend of the Internet as a source of health information, this
      study evaluated whether direct-to-consumer prescription drug websites for
      stigmatized illnesses contained stigma-reducing components: onset
      controllability, offset controllability, and recategorization. The authors
      examined the contents of the first-level homepages and the second-level pages in
      88 stand-alone websites for 15 different stigmatized conditions. Overall, about a
      third of the websites did not provide a direct link to detailed disease
      information on the homepage. On the homepages, three stigma-reducing components
      were rarely offered either through textual or visual cues. On the second level,
      in terms of textual cues, onset controllability and recategorization were the
      most prevalent, while offset controllability was relatively less frequent. There
      were no visual cues on the second level. Results point out the limited and
      insufficient stigma-reducing components of direct-to-consumer prescription drug
      websites. 

PMID- 24015753
TI  - In situ growth of well-dispersed CdS nanocrystals in semiconducting polymers.
AB  - A straight synthetic route to fabricate hybrid nanocomposite films of well
      dispersed CdS nanocrystals (NCs) in poly[2-methoxy-5-(2'-ethyl-hexyloxy)-1,4
      phenylene vinylene] (MEH-PPV) is reported. A soluble cadmium complex
      [Cd(SBz)2]2.MI, obtained by incorporating a Lewis base (1-methylimidazole, MI) on
      the cadmium bis(benzyl)thiol, is used as starting reagent in an in situ
      thermolytic process. CdS NCs with spherical shape nucleate and grow well below
      200 degrees C in a relatively short time (30 min). Photoluminescence spectroscopy
      measurements performed on CdS/MEH-PPV nanocomposites show that CdS
      photoluminescence peaks are totally quenched inside MEH-PPV, if compared to
      CdS/PMMA nanocomposites, as expected due to overlapping of the polymer absorption
      and CdS emission spectra. The CdS NCs are well-dispersed in size and
      homogeneously distributed within MEH-PPV matrix as proved by transmission
      electron microscopy. Nanocomposites with different precursor/polymer weight
      ratios were prepared in the range from 1:4 to 4:1. Highly dense materials,
      without NCs clustering, were obtained for a weight/weight ratio of 2:3 between
      precursor and polymer, making these nanocomposites particularly suitable for
      optoelectronic and solar energy conversion applications. 

PMID- 24015754
TI  - Microgravity effects on different stages of higher plant life cycle and
      completion of the seed-to-seed cycle.
AB  - Human inhabitation of Space requires the efficient realisation of crop
      cultivation in bioregenerative life-support systems (BLSS). It is well known that
      plants can grow under Space conditions; however, perturbations of many biological
      phenomena have been highlighted due to the effect of altered gravity and its
      possible interactions with other factors. The mechanisms priming plant responses
      to Space factors, as well as the consequences of such alterations on crop
      productivity, have not been completely elucidated. These perturbations can occur
      at different stages of plant life and are potentially responsible for failure of
      the completion of the seed-to-seed cycle. After brief consideration of the main
      constraints found in the most recent experiments aiming to produce seeds in
      Space, we focus on two developmental phases in which the plant life cycle can be
      interrupted more easily than in others also on Earth. The first regards seedling
      development and establishment; we discuss reasons for slow development at the
      seedling stage that often occurs under microgravity conditions and can reduce
      successful establishment. The second stage comprises gametogenesis and
      pollination; we focus on male gamete formation, also identifying potential
      constraints to subsequent fertilisation. We finally highlight how similar
      alterations at cytological level can not only be common to different processes
      occurring at different life stages, but can be primed by different stress
      factors; such alterations can be interpreted within the model of 'stress-induced
      morphogenic response' (SIMR). We conclude by suggesting that a systematic
      analysis of all growth and reproductive phases during the plant life cycle is
      needed to optimise resource use in plant-based BLSS. 

PMID- 24015755
TI  - Editorial Comment to Magnetic resonance spectroscopy imaging-directed transrectal
      ultrasound biopsy increases prostate cancer detection in men with prostate
      specific antigen between 4-10 ng/mL and normal digital rectal examination.

PMID- 24015757
TI  - Netherton syndrome associated with growth hormone deficiency.
AB  - Netherton syndrome (NS) is a rare autosomal recessive disorder characterized by
      ichthyosiform scaling, hair abnormalities, and variable atopic features.
      Mutations in the serine protease inhibitor Kazal type 5 (SPINK5) gene leading to
      lymphoepithelial Kazal-type-related inhibitor (LEKTI) deficiency cause NS. Growth
      retardation is a classic feature of NS, but growth hormone (GH) deficiency with
      subsequent response to GH therapy is not documented in the literature. It is
      proposed that a lack of inhibition of proteases due to a deficiency of LEKTI in
      the pituitary gland leads to the overprocessing of human GH in NS. Herein we
      report three patients with NS who had growth retardation associated with GH
      deficiency and responded well to GH therapy. 

PMID- 24015756
TI  - Adaptive evolution of the osmoregulation-related genes in cetaceans during
      secondary aquatic adaptation.
AB  - BACKGROUND: Osmoregulation was a primary challenge for cetaceans during the
      evolutionary transition from a terrestrial to a mainly hyperosmotic environment.
      Several physiological mechanisms have been suggested to maintain the water and
      salt balance in cetaceans, but their genetic and evolutionary bases remain poorly
      explored. The current study investigated the genes involved in osmoregulation in
      cetaceans and compared them with their counterparts in terrestrial mammals to
      test whether adaptive evolution occurred during secondary aquatic adaptation.
      RESULTS: The present study analyzed the molecular evolution of 11 osmoregulation
      related genes in 11 cetacean species, which represented all of the major cetacean
      clades. The results demonstrated positive selection acting on angiotensin
      converting enzyme (ACE), angiotensinogen (AGT), SLC14A2, and aquaporin 2 (AQP2).
      This evidence for the positive selection of AQP2 and SLC14A2 suggests that the
      adaptive evolution of these genes has helped to enhance the capacity for water
      and urea transport, thereby leading to the concentration of urine, which is an
      efficient mechanism for maintaining the water balance. By contrast, a series of
      positively selected amino acid residues identified in the ACE and AGT (two key
      members of the renin-angiotensin-aldosterone system, RAAS) proteins of cetaceans
      suggests that RAAS might have been adapted to maintain the water and salt balance
      in response to a hyperosmotic environment. Radical amino acid changes in
      positively selected sites were distributed among most internal and terminal
      branches of the cetacean phylogeny, which suggests the pervasively adaptive
      evolution of osmoregulation since the origin of cetaceans and their subsequent
      diversification. CONCLUSIONS: This is the first comprehensive analysis of the
      molecular evolution of osmoregulation-related genes in cetaceans in response to
      selection pressure from a generally hyperosmotic environment. Four genes, i.e.,
      AQP2, SLC14A2, ACE, and AGT were subject to positive selection in cetaceans,
      which suggests that cetaceans may have adapted to maintain their water and salt
      balance. This also suggests that cetaceans may have evolved an effective and
      complex mechanism for osmoregulation.

PMID- 24015758
TI  - Inheritance and vision.

PMID- 24015759
TI  - The science of exoplanets and their systems.
AB  - A scientific forum on "The Future Science of Exoplanets and Their Systems,"
      sponsored by Europlanet and the International Space Science Institute (ISSI) and
      co-organized by the Center for Space and Habitability (CSH) of the University of
      Bern, was held during December 5 and 6, 2012, in Bern, Switzerland. It gathered
      24 well-known specialists in exoplanetary, Solar System, and stellar science to
      discuss the future of the fast-expanding field of exoplanetary research, which
      now has nearly 1000 objects to analyze and compare and will develop even more
      quickly over the coming years. The forum discussions included a review of current
      observational knowledge, efforts for exoplanetary atmosphere characterization and
      their formation, water formation, atmospheric evolution, habitability aspects,
      and our understanding of how exoplanets interact with their stellar and galactic
      environment throughout their history. Several important and timely research areas
      of focus for further research efforts in the field were identified by the forum
      participants. These scientific topics are related to the origin and formation of
      water and its delivery to planetary bodies and the role of the disk in relation
      to planet formation, including constraints from observations as well as star
      planet interaction processes and their consequences for atmosphere-magnetosphere
      environments, evolution, and habitability. The relevance of these research areas
      is outlined in this report, and possible themes for future ISSI workshops are
      identified that may be proposed by the international research community over the
      coming 2-3 years.

PMID- 24015761
TI  - Continuous digital ECG analysis over accurate R-peak detection using adaptive
      wavelet technique.
AB  - Worldwide, health care segment is under a severe challenge to achieve more
      accurate and intelligent biomedical systems in order to assist healthcare
      professionals with more accurate and consistent data as well as reliability. The
      role of ECG in healthcare is one of the paramount importances and it has got a
      multitude of abnormal relations and anomalies which characterizes intricate
      cardiovascular performance image. Until the recent past, ECG instruments and
      analysis played the role of providing the PQRST signal as raw observational
      output either on paper or on a console or in a file having many diagnostic clues
      embedded in the signal left to the expert cardiologist to look out for
      characteristic intervals and to detect the cardiovascular abnormality. Methods
      and practises are required more and more, to automate this process of cardiac
      expertise using knowledge engineering and an intelligent systems approach. This
      paper presents one of the challenging R-peak detections to classify diagnosis and
      estimate cardio disorders in a fully automated signal processing sequence. This
      study used an adaptive wavelet approach to generate an appropriate wavelet for R
      signal identification under noise, baseband wandering and temporal variations of
      R-positions. This study designed an adaptive wavelet and successfully detected R-
      peak variations under various ECG signal conditions. The result and analysis of
      this method and the ways to use it for further purposes are presented here.

PMID- 24015760
TI  - HEXIM1 down-regulates hypoxia-inducible factor-1alpha protein stability.
AB  - We have previously reported on the inhibition of HIF-1alpha (hypoxia-inducible
      factor alpha)-regulated pathways by HEXIM1 [HMBA (hexamethylene-bis-acetamide)
      inducible protein 1]. Disruption of HEXIM1 activity in a knock-in mouse model
      expressing a mutant HEXIM1 protein resulted in increased susceptibility to the
      development of mammary tumours, partly by up-regulation of VEGF (vascular
      endothelial growth factor) expression, HIF-1alpha expression and aberrant
      vascularization. We now report on the mechanistic basis for HEXIM1 regulation of
      HIF-1alpha. We observed direct interaction between HIF-1alpha and HEXIM1, and
      HEXIM1 up-regulated hydroxylation of HIF-1alpha, resulting in the induction of
      the interaction of HIF-1alpha with pVHL (von Hippel-Lindau protein) and
      ubiquitination of HIF-1alpha. The up-regulation of hydroxylation involves HEXIM1
      mediated induction of PHD3 (prolyl hydroxylase 3) expression and interaction of
      PHD3 with HIF-1alpha. Acetylation of HIF-1alpha has been proposed to result in
      increased interaction of HIF-1alpha with pVHL and induced pVHL-mediated
      ubiquitination, which leads to the proteasomal degradation of HIF-1alpha. HEXIM1
      also attenuated the interaction of HIF-1alpha with HDAC1 (histone deacetylase 1),
      resulting in acetylation of HIF-1alpha. The consequence of HEXIM1 down-regulation
      of HIF-1alpha protein expression is attenuated expression of HIF-1alpha target
      genes in addition to VEGF and inhibition of HIF-1alpha-regulated cell invasion.

PMID- 24015763
TI  - Cu(2+)-responsive bimodal (optical/MRI) contrast agent for cellular imaging.
AB  - A water-soluble T1 magnetic resonance imaging contrast agent (1) has been
      synthesized. The bimodal contrast agent 1 responds to the Cu(2+) ion in living
      cells by enhancing the MRI modality signal whereas the optical signal gradually
      drops. This dual modality probe response depends on the cellular free copper ions
      in RAW 264.7 cells even at the micromolar level. 

PMID- 24015762
TI  - Intimate partner violence against women during and after pregnancy: a cross
      sectional study in Mumbai slums.
AB  - BACKGROUND: At least one-third of women in India experience intimate partner
      violence (IPV) at some point in adulthood. Our objectives were to describe the
      prevalence of IPV during pregnancy and after delivery in an urban slum setting,
      to review its social determinants, and to explore its effects on maternal and
      newborn health. METHODS: We did a cross-sectional study nested within the data
      collection system for a concurrent trial. Through urban community surveillance,
      we identified births in 48 slum areas and interviewed mothers ~6 weeks later.
      After collecting information on demographic characteristics, socioeconomic
      indicators, and maternal and newborn care, we asked their opinions on the
      justifiability of IPV and on their experience of it in the last 12 months.
      RESULTS: Of 2139 respondents, 35% (748) said that violence was justifiable if a
      woman disrespected her in-laws or argued with her husband, failed to provide good
      food, housework and childcare, or went out without permission. 318 (15%, 95% CI
      13, 16%) reported IPV in the year that included pregnancy and the postpartum
      period. Physical IPV was reported by 247 (12%, 95% CI 10, 13%), sexual IPV by 35
      (2%, 95% CI 1, 2%), and emotional IPV by 167 (8%, 95% CI 7, 9). 219 (69%) women
      said that the likelihood of IPV was either unaffected by or increased during
      maternity. IPV was more likely to be reported by women from poorer families and
      when husbands used alcohol. Although 18% of women who had suffered physical IPV
      sought clinical care for their injuries, seeking help from organizations outside
      the family to address IPV itself was rare. Women who reported IPV were more
      likely to have reported illness during pregnancy and use of modern methods of
      family planning. They were more than twice as likely to say that there were
      situations in which violence was justifiable (odds ratio 2.6, 95% CI 1.7, 3.4).
      CONCLUSIONS: One in seven women suffered IPV during or shortly after pregnancy.
      The elements of the violent milieu are mutually reinforcing and need to be taken
      into account collectively in responding to both individual cases and framing
      public health initiatives.

PMID- 24015764
TI  - Physiological and biomechanical responses to walking underwater on a non
      motorised treadmill: effects of different exercise intensities and depths in
      middle-aged healthy women.
AB  - Non-motorised underwater treadmills are commonly used in fitness activities.
      However, no studies have examined physiological and biomechanical responses of
      walking on non-motorised treadmills at different intensities and depths. Fifteen
      middle-aged healthy women underwent two underwater walking tests at two different
      depths, immersed either up to the xiphoid process (deep water) or the iliac crest
      (shallow water), at 100, 110, 120, 130 step-per-minute (spm). Oxygen consumption
      (VO2), heart rate (HR), blood lactate concentration, perceived exertion and step
      length were determined. Compared to deep water, walking in shallow water
      exhibited, at all intensities, significantly higher VO2 (+13.5%, on average) and
      HR (+8.1%, on average) responses. Water depth did not influence lactate
      concentration, whereas perceived exertion was higher in shallow compared to deep
      water, solely at 120 (+40%) and 130 (+39.4%) spm. Average step length was reduced
      as the intensity increased (from 100 to 130 spm), irrespective of water depth.
      Expressed as a percentage of maximum, average VO2 and HR were: 64-76% of peak VO2
      and 71-90% of maximum HR, respectively at both water depths. Accordingly, this
      form of exercise can be included in the "vigorous" range of exercise intensity,
      at any of the step frequencies used in this study.

PMID- 24015765
TI  - Pump and probe of ultrafast charge reorganization in small peptides: a
      computational study through sudden ionizations.
AB  - The ultrafast migratory dynamics of the nonstationary hole resulting from a
      sudden ionization of the small tetrapeptides, Trp-(Leu)3 and Tyr-(Ala)3, is
      studied using as input a high level quantum chemistry description of the
      electronic structure for extended conformers computed for frozen nuclei. The
      sudden ionization process prepares a localized electronic wavepacket that is a
      superposition of a few stationary states of the cation that are energetically
      allowed. The superposition evolves field-free until a second ionization to the
      dication. The wavelength and polarization of the first ultrashort VUV ionizing
      pulse can be used to tailor the amplitudes on the states of the cation and the
      initial localization of the hole. For these molecular chains that extend over 15
      A, the most efficient mechanism for charge migration is sequential, involving
      coherent transitions between neighbor and next neighbor amino-acid subunits. The
      migration of the hole is probed by a second sudden ionization leading to a
      dication peptide. Its time scale is in the range of a few to a dozen of
      femtoseconds depending on the initial state of the cation built by the ionization
      process. The computed angular distributions provide a clear signature of the
      field-free dynamics between the two sudden ionization processes. Our results are
      consistent with the experimental observation that the charge transfer is
      activated, meaning that an excess energy above the ionization potential of the
      cation is required for facile migration of charge. 

PMID- 24015766
TI  - Effect of arm exchange on the liquid-solid transition of dense suspensions of
      star polymers.
AB  - Star polymers with dynamic arm exchange are formed in water by self-assembly of
      amphiphilic diblock copolymers based on poly(ethylene oxide) end capped with a
      small hydrophobic block. The arm exchange was arrested in situ by photo-cross
      linking of the core. The effect of dynamic arm exchange on the osmotic
      compressibility and viscosity was investigated systematically as a function of
      the concentration and temperature. The discontinuous liquid-solid transition
      reported for dense polymeric micelle suspensions was found to be preserved after
      dynamic arm exchange was arrested in situ. The effect of cross-linking and
      aggregation number on the liquid-solid transition was investigated. 

PMID- 24015768
TI  - Mapping the electrical conductivity of poly(methyl methacrylate)/carbon black
      composites prior to and after shear.
AB  - In this letter, the electrical conductivity of disklike poly(methyl
      methacrylate)/carbon black composite samples was investigated prior to and after
      a shear process. Novel electrical conductivity maps of the samples as a function
      of the position were obtained. It was found that the electrical conductivity
      after angular averaging of the static (nonsheared) sample is, as expected,
      independent of the radius. However, for the sheared sample, the electrical
      conductivity is decreasing from the center to the outer rim of the sample. This
      is attributed to the interplay of destruction and buildup effects of the applied
      linear shear stress on the agglomerate network. 

PMID- 24015769
TI  - Single or dual coil defibrillation leads? Let's keep it simple!

PMID- 24015767
TI  - Drug discovery for neglected diseases: molecular target-based and phenotypic
      approaches.
AB  - Drug discovery for neglected tropical diseases is carried out using both target
      based and phenotypic approaches. In this paper, target-based approaches are
      discussed, with a particular focus on human African trypanosomiasis. Target-based
      drug discovery can be successful, but careful selection of targets is required.
      There are still very few fully validated drug targets in neglected diseases, and
      there is a high attrition rate in target-based drug discovery for these diseases.
      Phenotypic screening is a powerful method in both neglected and non-neglected
      diseases and has been very successfully used. Identification of molecular targets
      from phenotypic approaches can be a way to identify potential new drug targets. 

PMID- 24015770
TI  - Development of functional oral health literacy assessment instruments:
      application of literacy and cognitive theories.
AB  - OBJECTIVES: This paper describes the development of a new literacy assessment
      instrument, the Hong Kong Oral Health Literacy Assessment Task for Paediatric
      Dentistry (HKOHLAT-P). Its relationship to literacy theory is analyzed to
      establish content and face validity. Implications for construct validity are
      examined by analyzing cognitive demand to determine how "comprehension" is
      measured. METHODS: Key influences from literacy assessment were identified to
      analyze item development. Cognitive demand was analyzed using an established
      taxonomy. RESULTS: The HKOHLAT-P focuses on the functional domain of health
      literacy assessment. Items had strong content and face validity reflecting
      established principles from modern literacy theory. Inclusion of new text types
      signified relevant developments in the area of new literacies. Analysis of
      cognitive demand indicated that this instrument assesses the "comprehension"
      domain, specifically the areas of factual and procedural knowledge, with some
      assessment of conceptual knowledge. Metacognitive knowledge was not assessed.
      CONCLUSIONS: Comprehension tasks assessing patient health literacy predominantly
      examine functional health literacy at the lower levels of comprehension. Item
      development is influenced by the fields of situated and authentic literacy.
      Inclusion of content regarding multiliteracies is suggested for further research.
      Development of functional health literacy assessment instruments requires careful
      consideration of the clinical context in determining construct validity.

PMID- 24015772
TI  - Improved nonaqueous synthesis of TiO2 for dye-sensitized solar cells.
AB  - Nonaqueous synthesis routes have emerged as a powerful platform for directly
      obtaining diverse metal oxide nanoparticles with high crystallinity and tunable
      compositions. The benzyl alcohol (BA) route, for example, has been applied toward
      dozens of oxides including binary, ternary, and even more complex multimetal
      systems. Here we compare anatase nanoparticles made from the BA route with the
      traditional hydrothermal route. XPS measurements indicated that the BA route
      resulted in more reduced Ti states, corresponding to additional oxygen vacancies.
      These defects resulted in additional trap states, slower recombination, and
      slower charge transport. The performance of BA anatase was improved by
      incorporating niobium intended to suppress oxygen vacancies. The higher
      performance Nb-containing films were post-treated to yield a 7.96% power
      conversion efficiency (AM 1.5), similar to the state-of-the-art hydrolytic TiO2
      in the same configuration. 

PMID- 24015771
TI  - White matter changes in patients with friedreich ataxia after treatment with
      erythropoietin.
AB  - BACKGROUND AND PURPOSE: Erythropoietin (EPO) has received growing attention
      because of its neuroregenerative properties. Preclinical and clinical evidence
      supports its therapeutic potential in brain conditions like stroke, multiple
      sclerosis, and schizophrenia. Also, in Friedreich ataxia, clinical improvement
      after EPO therapy was shown. The aim of this study was to assess possible therapy
      associated brain white matter changes in these patients. METHODS: Nine patients
      with Friedreich ataxia underwent Diffusion Tensor Imaging (DTI) before and after
      EPO treatment. Tract-based spatial statistics was used for longitudinal
      comparison. RESULTS: We detected widespread longitudinal increase in fractional
      anisotropy and axial diffusivity (D||) in cerebral hemispheres bilaterally (P <
      .05, corrected), while no changes were observed within the cerebellum, medulla
      oblongata, and pons. CONCLUSIONS: To the best of our knowledge, this is the first
      DTI study to investigate the effects of EPO in a neurodegenerative disease.
      Anatomically, the diffusivity changes appear disease unspecific, and their
      biological underpinnings deserve further study.

PMID- 24015773
TI  - The unintended target: assessing nonsmokers' reactions to gain- and loss-framed
      antismoking public service announcements.
AB  - This study examined nonsmokers' emotional responses and intentions to promote
      smoking cessation after exposure to a gain- or loss-framed antismoking public
      service announcement (PSA). Participants were 183 nonsmokers, and results reveal
      that gain- and loss-framed antismoking PSAs elicited different types and levels
      of affect as a function of the message theme for the antismoking PSA. Although
      secondhand smoke PSAs elicited higher levels of anger toward smokers and fear of
      secondhand smoke, smoking addiction PSAs tended to elicit more guilt among
      nonsmokers. Elicited emotions were significant predictors of intentions, and
      overall, loss-framed appeals worked better than gain-framed appeals at increasing
      nonsmokers' intentions to talk to friends who smoke about quitting. 

PMID- 24015774
TI  - Platelet-to-Lymphocyte Ratio: One of the novel and valuable platelet indices in
      hemodialysis patients.

PMID- 24015775
TI  - Long-term clinical response to cardiac resynchronisation therapy under a
      multidisciplinary model.
AB  - BACKGROUND: Cardiac resynchronisation therapy (CRT) is established in the
      management of cardiac failure in patients with systolic dysfunction. Clinical
      response to CRT is not uniform, and response has been difficult to predict. AIM:
      Patient management within a high volume, multidisciplinary service focused on
      optimal delivery of CRT would improve response rates. METHODS: Four hundred and
      thirty-five consecutive patients who underwent CRT under a multidisciplinary
      heart failure service were enrolled prospectively over a 5-year period. Medically
      optimised, symptomatic patients with an ejection fraction (EF) <35%, widened QRS
      or abnormal dyssynchrony index were included. Left ventricular lead position was
      targeted anatomically to the segment of latest mechanical activation, and
      electrically to a site with maximal intrinsic intracardiac electrogram
      separation. Routine device and clinical follow up, as well as CRT optimisations,
      were performed at baseline and at 3-monthly intervals. Responders were defined as
      having an absolute reduction in left ventricular end-diastolic diameter >10% and
      an improvement in EF >5%. RESULTS: With a mean follow up of 53 +/- 11 months,
      response rate to CRT was 81%. Mean EF improved from 26 +/- 10% to 37 +/- 11%, and
      mean left ventricular end-diastolic diameter reduced from 68.6 +/- 9.2 mm to 57.8
      +/- 9.3 mm. Predictors of response were sinus rhythm, high dyssynchrony index and
      intrinsic electrical dyssynchrony >80 ms. Successful LV lead implantation at
      initial procedure was achieved in 99.1%, and at latest follow up 94.6% of initial
      LV leads were still active. CONCLUSION: CRT undertaken with a unit focus on
      optimal LV lead positioning and device optimisation, along with a
      multidisciplinary follow-up model, results in an excellent response rate to CRT.

PMID- 24015776
TI  - Managing heteroscedasticity in general linear models.
AB  - Heteroscedasticity refers to a phenomenon where data violate a statistical
      assumption. This assumption is known as homoscedasticity. When the
      homoscedasticity assumption is violated, this can lead to increased Type I error
      rates or decreased statistical power. Because this can adversely affect
      substantive conclusions, the failure to detect and manage heteroscedasticity
      could have serious implications for theory, research, and practice. In addition,
      heteroscedasticity is not uncommon in the behavioral and social sciences. Thus,
      in the current article, we synthesize extant literature in applied psychology,
      econometrics, quantitative psychology, and statistics, and we offer
      recommendations for researchers and practitioners regarding available procedures
      for detecting heteroscedasticity and mitigating its effects. In addition to
      discussing the strengths and weaknesses of various procedures and comparing them
      in terms of existing simulation results, we describe a 3-step data-analytic
      process for detecting and managing heteroscedasticity: (a) fitting a model based
      on theory and saving residuals, (b) the analysis of residuals, and (c)
      statistical inferences (e.g., hypothesis tests and confidence intervals)
      involving parameter estimates. We also demonstrate this data-analytic process
      using an illustrative example. Overall, detecting violations of the
      homoscedasticity assumption and mitigating its biasing effects can strengthen the
      validity of inferences from behavioral and social science data.

PMID- 24015777
TI  - Analysis of serum protein glycosylation by a differential lectin immunosorbant
      assay (dLISA).
AB  - BACKGROUND: Lectin immunosorbant assays (LISAs) have been widely used for
      analyzing protein glycosylation. However, the analysis of serum samples by LISAs
      could suffer from high sample-dependent background noise. The aim of this study
      is to develop a differential lectin immunosorbant assay (dLISA) with reduced
      background interferences. METHODS: For the analysis of protein glycosylation,
      dLISA establishes a dose-response curve for every serum sample. The sample is
      split into five aliquots. Four aliquots undergo differential removal of the
      glycoprotein of interest by immunoprecipitation. Then, all five aliquots are
      subject to two measurements: protein by immunoassay and protein glycans by LISA.
      A dose-response curve is established by plotting glycans signals on the y-axis
      and protein levels on the x-axis for all the aliquots. Slope of the curve,
      calculated by linear progression analysis and expressed as fluorescence per
      concentration of protein, is used for the measurement of protein glycosylation in
      the serum sample. RESULTS/CONCLUSIONS: To demonstrate the feasibility of the
      dLISA approach, we used recombinant, fucosylated tissue inhibitor of
      metallopeptidase 1 (TIMP-1) as the target glycoprotein. Magnetic beads based
      TIMP1 immunoassay and TIMP-1 UEA LISA were developed for the measurement of TIMP1
      protein and terminal alpha1, 2 fucosylated glycans on TIMP1, respectively. Serum
      samples supplemented with differentially fucosylated recombinant TIMP-1 were used
      to demonstrate that the slopes measured the TIMP-1 fucosylation, and were less
      prone to background interference.

PMID- 24015779
TI  - Very rapid DNA-templated reaction for efficient signal amplification and its
      steady-state kinetic analysis of the turnover cycle.
AB  - Oligonucleotide-templated reactions are powerful tools for the detection of
      nucleic acid sequences. One of the major scientific challenges associated with
      this technique is the rational design of non-enzyme-mediated catalytic templated
      reactions capable of multiple turnovers that provide high levels of signal
      amplification. Herein, we report the development of a nucleophilic aromatic
      substitution reaction-triggered fluorescent probe. The probe underwent a rapid
      templated reaction without any of the undesired background reactions. The
      fluorogenic reaction conducted in the presence of a template provided a 223-fold
      increase in fluorescence after 30 s compared with the nontemplated reaction. The
      probe provided an efficient level of signal amplification that ultimately enabled
      particularly sensitive levels of detection. Assuming a simple model for the
      templated reactions, it was possible to estimate the rate constants of the
      chemical reaction in the presence and in the absence of the template. From these
      kinetic analyses, it was possible to confirm that an efficient turnover cycle had
      been achieved, on the basis of the dramatic enhancement in the rate of the
      chemical reaction considered to be the rate-determining step. With maximized
      turnover efficiency, it was demonstrated that the probe could offer a high
      turnover number of 1500 times to enable sensitive levels of detection with a
      detection limit of 0.5 pM in the catalytic templated reactions. 

PMID- 24015778
TI  - Endosymbiosis in trypanosomatids: the genomic cooperation between bacterium and
      host in the synthesis of essential amino acids is heavily influenced by multiple
      horizontal gene transfers.
AB  - BACKGROUND: Trypanosomatids of the genera Angomonas and Strigomonas live in a
      mutualistic association characterized by extensive metabolic cooperation with
      obligate endosymbiotic Betaproteobacteria. However, the role played by the
      symbiont has been more guessed by indirect means than evidenced. Symbiont
      harboring trypanosomatids, in contrast to their counterparts lacking symbionts,
      exhibit lower nutritional requirements and are autotrophic for essential amino
      acids. To evidence the symbiont's contributions to this autotrophy, entire
      genomes of symbionts and trypanosomatids with and without symbionts were
      sequenced here. RESULTS: Analyses of the essential amino acid pathways revealed
      that most biosynthetic routes are in the symbiont genome. By contrast, the host
      trypanosomatid genome contains fewer genes, about half of which originated from
      different bacterial groups, perhaps only one of which (ornithine cyclodeaminase,
      EC:4.3.1.12) derived from the symbiont. Nutritional, enzymatic, and genomic data
      were jointly analyzed to construct an integrated view of essential amino acid
      metabolism in symbiont-harboring trypanosomatids. This comprehensive analysis
      showed perfect concordance among all these data, and revealed that the symbiont
      contains genes for enzymes that complete essential biosynthetic routes for the
      host amino acid production, thus explaining the low requirement for these
      elements in symbiont-harboring trypanosomatids. Phylogenetic analyses show that
      the cooperation between symbionts and their hosts is complemented by multiple
      horizontal gene transfers, from bacterial lineages to trypanosomatids, that
      occurred several times in the course of their evolution. Transfers occur
      preferentially in parts of the pathways that are missing from other eukaryotes.
      CONCLUSION: We have herein uncovered the genetic and evolutionary bases of
      essential amino acid biosynthesis in several trypanosomatids with and without
      endosymbionts, explaining and complementing decades of experimental results. We
      uncovered the remarkable plasticity in essential amino acid biosynthesis pathway
      evolution in these protozoans, demonstrating heavy influence of horizontal gene
      transfer events, from Bacteria to trypanosomatid nuclei, in the evolution of
      these pathways.

PMID- 24015781
TI  - Racial/ethnic differences in inpatient mortality and use of institutional
      postacute care following subarachnoid hemorrhage.
AB  - OBJECT: The goal of this study was to determine racial/ethnic differences in
      inpatient mortality rates and the use of institutional postacute care following
      subarachnoid hemorrhage (SAH) in the U.S. METHODS: A cross-sectional study of
      hospital discharges for SAH was conducted using the Nationwide Inpatient Sample
      for the years 2005-2010. Discharges with a principal diagnosis of SAH were
      identified and abstracted using the appropriate ICD-9-CM diagnostic code.
      Racial/ethnic groups were defined as white, black, Hispanic, Asian/Pacific
      Islander (API), and American Indian. Multinomial logistic regression analyses
      were performed comparing racial/ethnic groups with respect to the primary outcome
      of risk of in-hospital mortality and the secondary outcome of likelihood of
      discharge to institutional care. RESULTS: During the study period, 31,631
      discharges were related to SAH. Race/ethnicity was a significant predictor of
      death (p = 0.003) and discharge to institutional care (p <= 0.001). In the
      adjusted analysis, compared with white patients, API patients were at higher risk
      of death (OR 1.34, 95% CI 1.13-1.59) and Hispanic patients were at lower risk of
      death (OR 0.84, 95% CI 0.72-0.97). The likelihood of discharge to institutional
      care was statistically similar between white, Hispanic, API, and Native American
      patients. Black patients were more likely to be discharged to institutional care
      compared with white patients (OR 1.27, 95% CI 1.14-1.40), but were similar to
      white patients in the risk of death. CONCLUSIONS: Significant racial/ethnic
      differences are present in the risk of inpatient mortality and discharge to
      institutional care among patients with SAH in the US. Outcome is likely to be
      poor among API patients and best among Hispanic patients compared with other
      groups.

PMID- 24015782
TI  - Novel ambipolar orthogonal donor-acceptor host for blue organic light emitting
      diodes.
AB  - Ambipolar triplet hosts comprising 1,2,4-triazole and carbazole in ortho
      positions have been developed. The blue PHOLED has a high current efficiency of
      47.1 cd A(-1), power efficiency of 41.2 lm W(-1), and low efficiency roll-off.
      The high efficiency was attributed to the successful control of pi-conjugation
      through orthogonal arrangement of the substituents so that a wide T1-S0 gap could
      be maintained. 

PMID- 24015780
TI  - Family-based association analysis of alcohol dependence criteria and severity.
AB  - BACKGROUND: Despite the high heritability of alcohol dependence (AD), the genes
      found to be associated with it account for only a small proportion of its total
      variability. The goal of this study was to identify and analyze phenotypes based
      on homogeneous classes of individuals to increase the power to detect genetic
      risk factors contributing to the risk of AD. METHODS: The 7 individual DSM-IV
      criteria for AD were analyzed using latent class analysis (LCA) to identify
      classes defined by the pattern of endorsement of the criteria. A genome-wide
      association study was performed in 118 extended European American families (n =
      2,322 individuals) densely affected with AD to identify genes associated with AD,
      with each of the 7 DSM-IV criteria, and with the probability of belonging to 2 of
      3 latent classes. RESULTS: Heritability for DSM-IV AD was 61% and ranged from 17
      to 60% for the other phenotypes. A single nucleotide polymorphism (SNP) in the
      olfactory receptor OR51L1 was significantly associated (7.3 * 10(-8) ) with the
      DSM-IV criterion of persistent desire to, or inability to, cut down on drinking.
      LCA revealed a 3-class model: the "low-risk" class (50%) rarely endorsed any
      criteria and none met criteria for AD; the "moderate-risk" class (33%) endorsed
      primarily 4 DSM-IV criteria and 48% met criteria for AD; and the "high-risk"
      class (17%) manifested high endorsement probabilities for most criteria and
      nearly all (99%) met criteria for AD. One SNP in a sodium leak channel NALCN
      demonstrated genome-wide significance with the high-risk class (p = 4.1 * 10(-8)
      ). Analyses in an independent sample did not replicate these associations.
      CONCLUSIONS: We explored the genetic contribution to several phenotypes derived
      from the DSM-IV AD criteria. The strongest evidence of association was with SNPs
      in NALCN and OR51L1.

PMID- 24015783
TI  - Field-based Raman spectroscopic analyses of an Ordovician stromatolite.
AB  - Raman spectrometers are being miniaturized for future life-detection missions on
      Mars. Field-portable Raman spectrometers, which have similar spectral parameters
      to the instruments being developed for Mars rovers, have been used to examine
      extant biosignatures, but they have not yet been used to examine ancient
      biosignatures. Here, a portable Raman spectrometer was used to analyze an
      Ordovician stromatolite at the outcrop, revealing both its mineralogy and the
      presence of sp2 carbonaceous material. As stromatolites are often used as proof
      of the presence of life in Archean rocks and are searched for on Mars, the
      ability to analyze them in the field with no sample preparation has important
      ramifications for future Mars missions. However, these results also reveal that a
      785 nm excitation source, rather than the 532 nm excitation source planned for
      future missions, might be a better choice in the search for fossil biosignatures.

PMID- 24015784
TI  - Hemorrhagic acneiform lesions in a teenager as the initial presentation of
      granulomatosis with polyangiitis.
AB  - A 19-year-old girl presented with hemorrhagic acneiform lesions on the face for
      several months that was unresponsive to conventional acne treatment. A biopsy
      revealed a noninfectious suppurative granulomatous dermatitis with hemorrhage,
      possibly representing a ruptured folliculitis. A second biopsy revealed chronic
      granulomatous dermal inflammation and hemorrhage with foreign body giant cells
      non-infectious by stains. No vasculitis was noted in either biopsy. Later in her
      course she developed a severe sinusitis and eventually presented with severe
      fevers, rapid weight loss, sinusitis, and cough. Further workup produced the
      diagnosis of granulomatosis with polyangiitis (Wegener's granulomatosis). She
      rapidly improved with intravenous steroids and rituximab. To date, acneiform
      lesions have only been reported in young adult patients and may represent a
      clinical manifestation of granulomatosis with polyangiitis unique to this age
      group, as illustrated in our patient.

PMID- 24015785
TI  - The air-water interface determines the outcome of seeding during amyloidogenesis.
AB  - Amyloid formation is a hallmark of protein misfolding diseases (e.g. Type II
      diabetes mellitus). The energetically unfavourable nucleation step of
      amyloidogenesis can be accelerated by seeding, during which pre-formed aggregates
      act as templates for monomer recruitment. Hydrophobic-hydrophilic interfaces
      [e.g. AWI (air-water interface)] can also catalyse amyloidogenesis due to the
      surfactant properties of amyloidogenic polypeptides. Using thioflavin T
      fluorescence and electron microscopy, we demonstrate that the outcome of seeding
      on human islet amyloid polypeptide amyloidogenesis is dependent upon whether the
      AWI is present or absent and is dictated by seed type. Seeding significantly
      inhibits (with AWI) or promotes (without AWI) plateau height compared with
      seedless controls; with short fibrils being more efficient seeds than their
      longer counterparts. Moreover, promotion of nucleation by increasing monomer
      concentrations can only be observed in the absence of an AWI. Using biophysical
      modelling, we suggest that a possible explanation for our results may reside in
      lateral interactions between seeds and monomers determining the fibril mass
      formed in seeded reactions at steady-state. Our results suggest that in vivo
      hydrophobic-hydrophilic interfaces (e.g. the presence of membranes and their
      turnover rate) may dictate the outcome of seeding during amyloidogenesis and that
      factors affecting the size of the pre-aggregate may be important.

PMID- 24015787
TI  - Rapid weight-loss impairs simulated riding performance and strength in jockeys:
      implications for making-weight.
AB  - Despite the performance concerns of dehydration in other sports, there are
      currently no data on the effects of rapid weight-loss on the physical and
      cognitive performance of jockeys in a sport-specific context. In a randomised
      crossover design, eight Great Britain (GB) male licensed jockeys were assessed
      for chest strength, leg strength, simulated riding performance (assessed by
      maximum pushing frequency on a mechanical riding simulator during the final two
      furlongs of a simulated 2 mile race) and simple reaction time after performing 45
      min of exercise, during which euhydration was maintained (Control trial) or
      induced 2% dehydration (Rapid Weight-Loss trial). Reductions in both chest (-13.8
      +/- 3.03% vs. 0.62 +/- 1.04%) and leg strength (-4.8 +/- 4.8% vs. -0.56 +/- 2.5%)
      were greater in Rapid Weight-Loss compared with Control (P < 0.01 and P = 0.04,
      respectively). Similarly, reductions in simulated riding performance were also
      greater (P = 0.05) in Rapid Weight-Loss (-2.8 +/- 4.0%) compared with Control (
      0.07 +/- 1.5%), whereas there were no significant changes (P = 0.14) in simple
      reaction time. We conclude that a 2% reduction in body mass, as achieved by 45
      min of moderate-intensity exercise undertaken in a sweatsuit (a common method of
      inducing acute dehydration by jockeys), significantly impairs maximum pushing
      frequency during a simulated race. In addition, the observed reductions in
      strength may also increase the occupational hazards associated with race riding.

PMID- 24015786
TI  - Foreskin cutting beliefs and practices and the acceptability of male circumcision
      for HIV prevention in Papua New Guinea.
AB  - BACKGROUND: Male circumcision (MC) reduces HIV acquisition and is a key public
      health intervention in settings with high HIV prevalence, heterosexual
      transmission and low MC rates. In Papua New Guinea (PNG), where HIV prevalence is
      0.8%, there is no medical MC program for HIV prevention. There are however many
      different foreskin cutting practices across the country's 800 language groups.
      The major form exposes the glans but does not remove the foreskin. This study
      aimed to describe and quantify foreskin cutting styles, practices and beliefs. It
      also aimed to assess the acceptability of MC for HIV prevention in PNG. METHODS:
      Cross-sectional multicentre study, at two university campuses (Madang Province
      and National Capital District) and at two 'rural development' sites (mining site
      Enga Province; palm-oil plantation in Oro Province). Structured questionnaires
      were completed by participants originating from all regions of PNG who were
      resident at each site for study or work. RESULTS: Questionnaires were completed
      by 861 men and 519 women. Of men, 47% reported a longitudinal foreskin cut (cut
      through the dorsal surface to expose the glans but foreskin not removed); 43%
      reported no foreskin cut; and 10% a circumferential foreskin cut (complete
      removal). Frequency and type of cut varied significantly by region of origin (p <
      .001). Most men (72-82%) were cut between the ages of 10-20 years. Longitudinal
      cuts were most often done in a village by a friend, with circumferential cuts
      most often done in a clinic by a health professional. Most uncut men (71%) and
      longitudinal cut men (84%) stated they would remove their foreskin if it reduced
      the risk of HIV infection. More than 95% of uncut men and 97% of longitudinal cut
      men would prefer the procedure in a clinic or hospital. Most men (90%) and women
      (74%) stated they would remove the foreskin of their son if it reduced the risk
      of HIV infection. CONCLUSION: Although 57% of men reported some form of foreskin
      cut only 10% reported the complete removal of the foreskin, the procedure on
      which international HIV prevention strategies are based. The acceptability of MC
      (complete foreskin removal) is high among men (for themselves and their sons) and
      women (for their sons). Potential MC services need to be responsive to the
      diversity of beliefs and practices and consider health system constraints. A
      concerted research effort to investigate the potential protective effects of
      longitudinal cuts for HIV acquisition is essential given the scale of
      longitudinal cuts in PNG.

PMID- 24015788
TI  - Termination of persistent atrial fibrillation during ablation: finding the needle
      in the haystack.

PMID- 24015789
TI  - NMR studies on effects of tetraalkylammonium bromides on micellization of sodium
      dodecylsulfate.
AB  - The effects of tetraalkylammonium bromides (TAABs) on the micellization of sodium
      dodecylsulfate (SDS) are studied using pyrene solubilization and several nuclear
      magnetic resonance (NMR) techniques. Two-dimensional nuclear Overhauser effect
      spectroscopy (2D NOESY) experiments confirm that tetraalkylammonium (TAA(+)) ions
      associate with SDS to form mixed micelles. TAA(+) ions attach to the surface of
      the mixed micelles and become inserted into the hydrophobic core of the mixed
      micelles. Because TAA(+) ions appear in the hydrophobic interior of the TAA-SDS
      mixed micelles, the micropolarity inside the mixed micelles sensed by pyrene
      might not reflect the true hydrophobicity of the micellar core. Using proton
      chemical shift analysis, the degree of hydration on the surface of the mixed
      micelles is determined from the chemical shift change of SDS alpha-CH2 protons.
      The self-diffusion coefficients of SDS and TAA(+) ions in the TAAB/SDS/D2O
      solutions are measured by using pulse-field gradient NMR, and the fraction of
      TAA(+) ions associated with the SDS to form the mixed micelles is calculated from
      the self-diffusion data. Moreover, secondary micelle formation for SDS and TAA(+)
      ions is observed on the basis of (1)H chemical shift analysis and the self
      diffusion data. The 2D NOESY experiments also reveal unusual tumbling behavior of
      SDS alkyl protons. For Pr4NBr/SDS and Bu4NBr/SDS solutions, positive and negative
      nuclear Overhauser effects are simultaneously observed among the SDS alkyl
      protons. 

PMID- 24015790
TI  - Influence of capillary bridge formation onto the silica nanoparticle interaction
      studied by grand canonical Monte Carlo simulations.
AB  - Adhesion forces between nanoparticles strongly depend on the amount of adsorbed
      condensed water from ambient atmosphere. Liquid water forms bridges in the
      cavities separating the particles, giving rise to the so-called capillary forces
      which in most cases dominate the van der Waals and long-range electrostatic
      interactions. Capillary forces promote the undesirable agglomeration of particles
      to large clusters, thereby hindering the flowability of dry powders in process
      containers. In process engineering macroscopic theories based on the Laplace
      pressures are used to estimate the strength of the capillary forces. However,
      especially for low relative humidity and when the wetting of rough or small
      nanoparticles is studied, those theories can fail. Molecular dynamic simulations
      can help to give better insight into the water-particle interface. The simulated
      force versus distance curve as well as adhesion forces and the adsorption
      isotherm for silica nanoparticles at varying relative humidity will be discussed
      in comparison to experiments, theories, and simulations. 

PMID- 24015791
TI  - Maintaining perspective and balance.

PMID- 24015792
TI  - On creating an effective future.

PMID- 24015793
TI  - Assuring content integrity.
AB  - It is important to assure that content integrity is maintained for the
      educational activities you provide. This column addresses the key components of
      content integrity and how to be sure they are implemented in your planning
      process.

PMID- 24015794
TI  - The transition to registered professional nurse: one health system's response.
AB  - This article explores one large health system's approach to the challenges that
      both organizations and newly graduated nurses experience. A few of the available
      transitional support programs are highlighted.

PMID- 24015795
TI  - Developing confidence decreases guessing and increases competency.
AB  - Validating competency to meet accreditation and safety demands is a major
      challenge many organizations face. Traditional testing methods may only reflect
      guessing and may not capture the amount of misinformation nurses are using for
      critical decision making. Using a confidence-based learning methodology allows
      learners to correct misinformation and gain confidence and competency.

PMID- 24015797
TI  - Pitfalls in susceptibility-weighted imaging of the pediatric brain.
AB  - Susceptibility-weighted imaging (SWI) is a recently developed high resolution 3
      dimensional gradient-echo pulse sequence that accentuates the magnetic
      susceptibility of blood, calcium, and nonheme iron. The clinical applications of
      SWI in pediatric neuroimaging have significantly expanded recently. Potential
      pitfalls related to blood oxygenation, blood flow, magnetic field strength, and
      misinterpretation of localization as well as possible mimickers may be misleading
      and affect the correct interpretation of SWI images. Familiarity with these
      potential diagnostic pitfalls is important to prevent misdiagnosis and will
      further enhance the ability of SWI in becoming a robust and reliable technique. 

PMID- 24015798
TI  - Health Care Workers' Suggestions for Improving HIV-Related Maternal Care in South
      Africa: "Listen to Us".
AB  - INTRODUCTION: South Africa has the highest rate of individuals infected with HIV
      in the world. Women in particular are at increased risk for HIV infection and
      typically receive care from nurses and midwives who are on the front lines of
      health care policy and program implementation. The primary objective of this
      study was to compile and analyze suggestions generated by health care
      professionals on how to improve HIV-related maternal care in South Africa. This
      information can then be used to inform the direction of future programs across
      the country and beyond. METHODS: Two hundred forty-nine nurses, midwives, and
      nursing students enrolled in a South African university completed surveys as part
      of this qualitative cross-sectional study. Responses were transcribed and coded
      by independent researchers who met frequently to discuss and come to consensus on
      emerging themes. RESULTS: Four primary strategies to improve HIV-related maternal
      care emerged from the data. These women's health professionals suggested
      improving education, increasing grassroots-level participation by government
      officials, improving resources, and developing strategies aimed at decreasing the
      risk of secondary transmission of HIV. DISCUSSION: Nurses and midwives are
      frontline health care professionals who are in unique positions to offer feedback
      on how HIV-related maternal care can be improved. The identified strategies
      should be integrated into future programs, and human rights implications must be
      examined.

PMID- 24015800
TI  - Correction: Predictive value of IgE/IgG4 antibody ratio in children with egg
      allergy.

PMID- 24015799
TI  - Inflammatory bowel disease cancer surveillance in a tertiary referral hospital:
      attitudes and practice.
AB  - BACKGROUND: Physician adherence to guidelines for colorectal cancer (CRC)
      surveillance in inflammatory bowel disease (IBD) is often poor. This may lead to
      adverse patient outcomes and excess endoscopic workload. AIMS: To assess the
      attitudes and practice of IBD specialists in a tertiary centre towards
      colonoscopic surveillance. METHODS: First, a questionnaire evaluating attitudes
      and approach to CRC surveillance was issued to 36 clinicians at one tertiary
      referral hospital. Second, a retrospective audit of IBD surveillance colonoscopy
      practice over a 2-year period was performed. RESULTS: Questionnaire response rate
      was 97%. Sixty-nine per cent of respondents were aware of, and used, Australian
      guidelines. Surveillance was undertaken by all clinicians in patients with
      extensive colitis, 83% in patients with left-sided colitis and 51% in patients
      with proctitis. Seventy-six per cent used chromoendoscopy, and 47% took 10 to 20
      random biopsies. Colectomy was considered appropriate in 0% for unifocal low
      grade dysplasia, 35% for multifocal low-grade dysplasia and 83% for high-grade
      dysplasia. Sixty-six per cent would remove elevated dysplastic lesions
      endoscopically. The audit identified 103 surveillance colonoscopies in 81
      patients. Chromoendoscopy was used in 21% of cases, and the median number of
      random biopsies was 13. Sixty-two per cent of colonoscopies were performed
      outside the guidelines in relation to colonoscopic frequency. Following
      colonoscopy, an appropriate recommendation for subsequent surveillance was
      documented in 40% of cases. CONCLUSIONS: Knowledge and practice of CRC
      surveillance in IBD vary among specialist clinicians and often deviate from
      guidelines. Many clinicians perform surveillance earlier and more frequently than
      recommended. These findings have implications for patient outcomes and workload.

PMID- 24015801
TI  - DNA polymerase V kinetics support the instructive nature of an oxidized abasic
      lesion in Escherichia coli.
AB  - Translesion synthesis past an oxidized abasic site, 2-deoxyribonolactone, in
      Escherichia coli results in high levels of dG incorporation and is dependent upon
      DNA polymerase V (Pol V). Kinetic experiments performed here affirm that Pol V
      preferentially incorporates dG opposite 2-deoxyribonolactone (L). Pol V
      discriminates between dG and dA on the basis of the apparent KD, suggesting that
      L provides instructive structural information to the enzyme despite lacking a
      Watson-Crick base. 

PMID- 24015802
TI  - Involvement of the ABCG37 transporter in secretion of scopoletin and derivatives
      by Arabidopsis roots in response to iron deficiency.
AB  - Studies of Iron (Fe) uptake mechanisms by plant roots have focussed on Fe(III)
      siderophores or Fe(II) transport systems. Iron deficency also enhances root
      secretion of flavins and phenolics. However, the nature of these compounds, their
      transport outside the roots and their role in Fe nutrition are largely unknown.
      We used HPLC/ESI-MS (TOF) and HPLC/ESI-MS/MS (ion trap) to characterize
      fluorescent phenolic-type compounds accumulated in roots or exported to the
      culture medium of Arabidopsis plants in response to Fe deficiency. Wild-type and
      mutant plants altered either in phenylpropanoid biosynthesis or in the ABCG37
      (PDR9) ABC transporter were grown under standard or Fe-deficient nutrition
      conditions and compared. Fe deficiency upregulates the expression of genes
      encoding enzymes of the phenylpropanoid pathway and leads to the synthesis and
      secretion of phenolic compounds belonging to the coumarin family. The ABCG37 gene
      is also upregulated in response to Fe deficiency and coumarin export is impaired
      in pdr9 mutant plants. Therefore it can be concluded that: Fe deficiency induces
      the secretion of coumarin compounds by Arabidopsis roots; the ABCG37 ABC
      transporter is required for this secretion to take place; and these compounds
      improved plant Fe nutrition. 

PMID- 24015804
TI  - Radiographic localization and isometry of the origin and insertion of the canine
      cranial cruciate ligament.
AB  - OBJECTIVE: To radiographically define the anatomic origin and insertion of the
      cranial cruciate ligament translated to the lateral radiographic projection of
      the stifle (CrCL-Lo and CrCL-Li, respectively), to correlate these landmarks for
      identification of the CrCL-Lo intraoperatively, and to compare the isometry of
      the CrCL-Lo to the lateral fabella. STUDY DESIGN: Experimental study. SAMPLE
      POPULATION: Pelvic limbs (n = 12) from dogs weighing 13-26 kg. METHODS: A
      radiographic quadrant method was used to localize the CrCL-Lo. Mediolateral
      radiographic projections of each stifle were taken through a range of motion.
      Maximum percent change in length between each tibial marker and femoral marker
      during range of motion determined isometry. RESULTS: The CrCL-Lo is located at
      the caudal 33% and distal 50% of the lateral femoral condyle using Blumensaat's
      line or a line from the origin of the long digital extensor (LDE) to the lateral
      fabella, with no significant difference (P = .766) between the 2 reference lines.
      The CrCL-Li is located at the proximal 20% of the tibial plateau. No significant
      difference (P < .05) in isometry was found between the CrCL-Lo and lateral
      fabella. CONCLUSION: The CrCL-Lo is located at the caudal 1/3 and distal 1/2 of
      the lateral femoral condyle. The CrCL-Lo and lateral fabella are not
      significantly different in isometry when used as a proximal anchor point in
      extracapsular stifle stabilization.

PMID- 24015803
TI  - An alternative pathway to ribonucleoside beta-hydroxyphosphonate analogues and
      related prodrugs.
AB  - Nucleoside beta-(S)-hydroxyphosphonate analogues have recently proven to be
      interesting bioactive compounds as 5'-nucleotidase inhibitors. These derivatives
      were obtained in a pyrimidine series through an ex-chiral pool pathway or the
      stereoselective reduction of a beta-ketophosphonate intermediate. Herein, an
      original synthesis of these compounds using nucleoside epoxide intermediates,
      containing either a pyrimidine or a purine as nucleobase, was explored and
      allowed the direct synthesis of the corresponding bis S-acyl-2-thioethyl (SATE)
      prodrugs. 

PMID- 24015805
TI  - Functional regeneration of recurrent laryngeal nerve injury during thyroid
      surgery using an asymmetrically porous nerve guide conduit in an animal model.
AB  - BACKGROUND: Vocal cord paralysis (VCP) caused by recurrent laryngeal nerve (RLN)
      damage during thyroidectomy commonly results in serious medico-legal problems.
      The purpose of this study was to evaluate the usefulness of an asymmetrically
      porous polycaprolactone (PCL)/Pluronic F127 nerve guide conduit (NGC) for
      functional regeneration in a RLN injury animal model. METHODS: A biodegradable,
      asymmetrically porous PCL/F127 NGC with selective permeability was fabricated for
      use in this study. A 10-mm segment of left RLN was resected in 28 New Zealand
      white rabbits, and then an asymmetrically porous NGC or a nonporous silicone tube
      was interposed between both stumps and securely fixed. Vocal cord mobility was
      endoscopically evaluated at one, four, and eight weeks postoperatively. Nerve
      growth through NGCs was assessed by toluidine blue staining, and thyroarytenoid
      (TA) muscle atrophy was evaluated by hematoxylin and eosin staining.
      Immunohistochemical stainings for acetylcholinesterase (AchE), anti-neurofilament
      (NF), and anti-S100 protein were also conducted, and transmission electron
      microscopy (TEM) was used to evaluate functional nerve regeneration. RESULTS: At
      eight weeks postoperatively, endoscopic evaluations showed significantly better
      recovery from VCP in the asymmetrically porous PCL/F127 NGC group (6 of 10
      rabbits) than in the silicone tube group (1 of 10 rabbits). Continued nerve
      growth on the damaged nerve endings was observed with time in the asymmetrically
      porous PCL/F127 NGC-interposed RLNs. TA muscle dimensions and AchE expressions in
      TA muscle were significantly greater in the asymmetrically porous PCL/F127 NGC
      group than in the silicone tube group. Furthermore, immunohistochemical staining
      revealed the expression of NF and S100 protein in the regenerated nerves in the
      asymmetrically porous PCL/F127 NGC group at eight weeks postoperatively, and at
      this time, TEM imaging showed myelinated axons in the regenerated RLNs.
      CONCLUSION: The study shows that asymmetrically porous PCL/F127 NGC provides a
      favorable environment for RLN regeneration and that it has therapeutic potential
      for the regeneration of RLN damage.

PMID- 24015806
TI  - Habitability on Mars from a microbial point of view.
AB  - Extraterrestrial habitability is a complex notion. We briefly review what is
      known about the origin of life on Earth, that is, life based on carbon chemistry
      and water. We then discuss habitable conditions (past and present) for
      established life and for the survival of microorganisms. Based on these elements,
      we propose to use the term habitable only for conditions necessary for the origin
      of life, the proliferation of life, and the survival of life. Not covered by this
      term would be conditions necessary for prebiotic chemistry and conditions that
      would allow the recognition of extinct or hibernating life. Finally, we apply
      this concept to the potential emergence of life on Mars where suitable conditions
      for life to start, proliferate, and survive have been heterogeneous throughout
      its history. These considerations have a profound impact on the nature and
      distribution of eventual traces of martian life, or any precursor, and must
      therefore inform our search-for-life strategies.

PMID- 24015807
TI  - Bacteria as bullies: effects of linguistic agency assignment in health message.
AB  - When describing health threats, communicators can assign agency to the threat
      (e.g., "Hepatitis C has infected 4 million Americans") or to humans (e.g., "Four
      million Americans have contracted hepatitis C"). In an online experiment, the
      authors explored how assignment of agency affects perceptions of susceptibility
      and severity of a health threat, response efficacy, self-efficacy, fear arousal,
      and intentions to adopt health-protective recommendations. Participants were 719
      individuals recruited through Mechanical Turk ( www.mturk.com ), a crowdsource
      labor market run by Amazon ( www.amazon.com ). The participants were assigned
      randomly to read 1 of 8 flyers defined by a 2*4 (Agency Assignment*Topic)
      factorial design. Each flyer examined 1 health threat (E. coli, necrotizing
      fasciitis, salmonella, or Carbapenem-resistant Klebsiella pneumoniae) and was
      written in language that emphasized bacterial or human agency. Perceived
      susceptibility and severity were highest when bacterial agency language was used.
      Response efficacy, self-efficacy, and fear arousal were not significantly
      affected by agency assignment. Participants reported stronger intentions to adopt
      recommendations when bacteria agency language was used, but this effect did not
      reach conventional standards of significance (p < .051). The authors concluded
      that health communicators can increase target audiences' perceptions of
      susceptibility and severity by assigning agency to the threat in question when
      devising health messages. 

PMID- 24015808
TI  - Avoiding steam explosions during catheter ablation: "stopping before popping".

PMID- 24015809
TI  - Nanoparticles that sense thrombin activity as synthetic urinary biomarkers of
      thrombosis.
AB  - Thrombin is a serine protease and regulator of hemostasis that plays a critical
      role in the formation of obstructive blood clots, or thrombosis, that is a life
      threatening condition associated with numerous diseases such as atherosclerosis
      and stroke. To detect thrombi in living animals, we design and conjugate thrombin
      sensitive peptide substrates to the surface of nanoparticles. Following
      intravenous infusion, these "synthetic biomarkers" survey the host vasculature
      for coagulation and, in response to substrate cleavage by thrombin, release
      ligand-encoded reporters into the host urine. To detect the urinary reporters, we
      develop a companion 96-well immunoassay that utilizes antibodies to bind
      specifically to the ligands, thus capturing the reporters for quantification.
      Using a thromboplastin-induced mouse model of pulmonary embolism, we show that
      urinary biomarker levels differentiate between healthy and thrombotic states and
      correlate closely with the aggregate burden of clots formed in the lungs. Our
      results demonstrate that synthetic biomarkers can be engineered to sense vascular
      diseases remotely from the urine and may allow applications in point-of-care
      diagnostics. 

PMID- 24015811
TI  - A family of porous lonsdaleite-e networks obtained through pillaring of decorated
      kagome lattice sheets.
AB  - A new and versatile class of metal-organic materials (MOMs) with augmented
      lonsdaleite-e (lon-e-a) topology is presented herein. This family of lon-e nets
      are built by pillaring of hexagonal two-dimensional kagome (kag) lattices
      constructed from well-known [Zn2(CO2R)4] paddlewheel molecular building blocks
      (MBBs) connected by 1,3-benzenedicarboxylate (bdc(2-)) linkers. The pillars are
      [Cr3(MU3-O)(RCO2)]6 trigonal prismatic primary MBBs decorated by six pyridyl
      moieties (tp-PMBB-1). The three-fold symmetry (D3h) of tp-PMBB-1 is complementary
      with the alternating orientation of the axial sites of the paddlewheel MBBs and
      enables triple cross-linking of the kag layers by each pillar. These MOMs
      represent the first examples of axial-to-axial pillared undulating kag layers,
      and they are readily fine-tuned because the bdc(2-) moieties can be varied at
      their 5-position without changing the overall structure. This lon-e platform
      possesses functionalized hexagonal channels since the kag lattices are
      necessarily eclipsed. The effects of the substituent at the 5-positions of the
      bdc(2-) linkers upon gas adsorption, particularly the heats of adsorption of
      carbon dioxide and methane, were studied. 

PMID- 24015810
TI  - Factors associated with parental smoking in the presence of school-aged children:
      a cross-sectional study.
AB  - BACKGROUND: In 2009, the Tobacco Hazards Prevention Act (Taiwan) was amended to
      more effectively restrict smoking in indoor public places and workplaces in
      Taiwan. However, the lack of prohibitions for smoking in private homes may place
      family members at increased risk for exposure to environmental tobacco smoke
      (ETS). The aim of our study was to determine the factors associated with parental
      smoking in the presence of children at home. METHODS: In 2010, we performed a
      cross-sectional study of factors associated with parental smoking in the presence
      of children at home in Taiwan using self-administered questionnaires. Quota
      sampling was used to select five primary schools from four different regions of
      Taiwan. Parents were surveyed to identify parental smokers and 307 parental
      smokers were selected for participation in our study. Questionnaire data
      regarding parental smoking in the presence of children at home and related
      interactions among family members were analyzed. Hierarchical logistic regression
      was used to determine the best-fit model for examining the relationships among
      the variables related to parental smoking in the presence of children at home.
      RESULTS: Two-thirds of parents who smoked reported smoking in the presence of
      their children. The results of the hierarchical logistic regression analysis
      identified the smokers' compliance with their family's antismoking responses,
      mutual agreement with smoking bans, daily smoking, smoking more than 20
      cigarettes per day, the education level of the parental smoker, and the annual
      family income as determinants of smoking in the presence of children at home.
      CONCLUSIONS: Households with smoking parents should be targeted for interventions
      to encourage the adoption and enforcement of home smoking bans. Educational
      interventions that promote smoke-free homes for children and provide support to
      help parents stop smoking are critical factors in reducing the frequency of
      children's ETS exposure in the home.

PMID- 24015812
TI  - Association of the MTHFR 1298A>C (rs1801131) polymorphism with speed and strength
      sports in Russian and Polish athletes.
AB  - It has been suggested that DNA hypomethylation because of poorer effectiveness of
      the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme induces muscular
      growth. We hypothesised that the common, functional 1298A>C polymorphism in the
      MTHFR gene is associated with athletic status. To test this hypothesis, we
      investigated the distribution of the 1298A>C variant in Polish (n = 302) and
      Russian (n = 842) athletes divided into four groups: endurance, strength
      endurance, sprint-strength and strength-endurance, as well as in 1540 control
      participants. We found different genotypes (the AC heterozygote advantage) and
      allele distributions among sprint-strength athletes and strength athletes than
      the groups of sedentary controls for each nationality. In the combined study, the
      allelic frequencies for the 1298C variant were 35.6% in sprint-strength athletes
      (OR 1.18 [1.02-1.36], P = 0.024 vs. controls) and 38.6% in strength athletes (OR
      1.34 [1.10-1.64], P = 0.003 vs. controls). The results of the initial and
      repetition studies as well as the combined analysis suggest that the functional
      1298A>C polymorphism in the MTHFR gene is associated with athletic status. The
      presence of the C allele seems to be beneficial in sprint-strength and strength
      athletes. It needs to be established whether and to what extent this effect is
      mediated by alteration in DNA methylation status.

PMID- 24015813
TI  - Experimental and theoretical studies on the fragmentation of gas-phase uranyl-,
      neptunyl-, and plutonyl-diglycolamide complexes.
AB  - Fragmentation of actinyl(VI) complexes U(VI)O2(L)2(2+), Np(VI)O2(L)2(2+), and
      Pu(VI)O2(L)2(2+) (L = tetramethyl-3-oxa-glutaramide, TMOGA) produced by
      electrospray ionization was examined in the gas phase by collision induced
      dissociation (CID) in a quadrupole ion trap mass spectrometer. Cleavage of the C
      O(ether) bond was observed for all three complexes, with dominant products being
      U(VI)O2(L)(L-86)(+) with charge reduction, and Np(VI)O2(L)(L-101)(2+) and
      Pu(VI)O2(L)(L-101)(2+) with charge conservation. The neptunyl and plutonyl
      complexes also exhibited substantial L(+) loss to give pentavalent complexes
      Np(V)O2(L)(+) and Pu(V)O2(L)(+), whereas the uranyl complex did not, consistent
      with the comparative An 5f-orbital energies and the An(VI)O2(2+)/An(V)O2(+) (An =
      U, Np, Pu) reduction potentials. CID of Np(V)O2(L)2(+) and Pu(V)O2(L)2(+) was
      dominated by neutral ligand loss to form Np(V)O2(L)(+) and Pu(V)O2(L)(+), which
      hydrated by addition of residual water in the ion trap; U(V)O2(L)2(+) was not
      observed. Theoretical calculations of the structures and bonding of the
      An(VI)O2(L)2(2+) complexes using density functional theory reveal that the metal
      centers are coordinated by six oxygen atoms from two TMOGA ligands.

PMID- 24015815
TI  - Your patient has died ... but your work is not done.

PMID- 24015814
TI  - Transitions between Andean and Amazonian centers of endemism in the radiation of
      some arboreal rodents.
AB  - BACKGROUND: The tropical Andes and Amazon are among the richest regions of
      endemism for mammals, and each has given rise to extensive in situ radiations.
      Various animal lineages have radiated ex situ after colonizing one of these
      regions from the other: Amazonian clades of dendrobatid frogs and passerine birds
      may have Andean ancestry, and transitions from the Amazon to Andes may be even
      more common. To examine biogeographic transitions between these regions, we
      investigated the evolutionary history of three clades of rodents in the family
      Echimyidae: bamboo rats (Dactylomys-Olallamys-Kannabateomys), spiny tree-rats
      (Mesomys-Lonchothrix), and brush-tailed rats (Isothrix). Each clade is
      distributed in both the Andes and Amazonia, and is more diverse in the lowlands.
      We used two mitochondrial (cyt-b and 12S) and three nuclear (GHR, vWF, and RAG1)
      markers to reconstruct their phylogenetic relationships. Tree topologies and
      ancestral geographic ranges were then used to determine whether Andean forms were
      basal to or derived from lowland radiations. RESULTS: Four biogeographic
      transitions are identified among the generic radiations. The bamboo rat clade
      unambiguously originated in the Amazon ca. 9 Ma, followed by either one early
      transition to the Andes (Olallamys) and a later move to the Amazon (Dactylomys),
      or two later shifts to the Andes (one in each genus). The Andean species of both
      Dactylomys and Isothrix are sister to their lowland species, raising the
      possibility that highland forms colonized the Amazon Basin. However, uncertainty
      in their reconstructed ancestral ranges obscures the origin of these transitions.
      The lone Andean species of Mesomys is confidently nested within the lowland
      radiation, thereby indicating an Amazon-to-Andes transition ca. 2 Ma.
      CONCLUSIONS: Differences in the timing of these biogeographic transitions do not
      appear to explain the different polarities of these trees. Instead, even within
      the radiation of a single family, both Andean and Amazonian centers of endemism
      appear enriched by lineages that originated in the other region. Our survey of
      other South American lineages suggests a pattern of reciprocal exchange between
      these regions-among mammals, birds, amphibians, and insects we found no fewer
      than 87 transitions between the Andes and Amazon from Miocene-Pleistocene.
      Because no clear trend emerges between the timing and polarity of transitions, or
      in their relative frequency, we suggest that reciprocal exchange between tropical
      highland and lowland faunas in South America has been a continual process since
      ca. 12 Ma.

PMID- 24015816
TI  - Life is a marketplace.

PMID- 24015817
TI  - Paradox of hope.

PMID- 24015818
TI  - Assessment of the contribution of NAD(P)H-dependent quinone oxidoreductase 1
      (NQO1) to the reduction of vitamin K in wild-type and NQO1-deficient mice.
AB  - NQO1 [NAD(P)H quinone oxidoreductase 1; also known as DT-diaphorase] is a
      cytosolic enzyme that catalyses the two-electron reduction of various quinones
      including vitamin K. The enzyme may play a role in vitamin K metabolism by
      reducing vitamin K to vitamin K hydroquinone for utilization in the post
      translational gamma-glutamyl carboxylation reactions required by several proteins
      involved in blood coagulation. The aim of the present study was to assess the
      contribution of NQO1 to vitamin K reduction and haemostasis in an in vivo model.
      We examined the contribution of NQO1 to haemostasis by examining survival rates
      in mice poisoned with the anticoagulant warfarin. Supraphysiological amounts of
      vitamin K sufficiently reversed the effects of warfarin in both wild-type and
      NQO1-deficient mice. Additionally, vitamin K reductase activities distinct from
      VKOR (vitamin K epoxide reductase) and NQO1 were measured in vitro from both wild
      type and NQO1-defecient mice. The results of the present study suggest that NQO1
      does not play a major role in the production of vitamin K hydroquinone and
      supports the existence of multiple vitamin K reduction pathways. The properties
      of a NAD(P)H-dependent vitamin K reductase different from NQO1 are described.

PMID- 24015819
TI  - Industrial-strength ecology: trade-offs and opportunities in algal biofuel
      production.
AB  - Microalgae represent one of the most promising groups of candidate organisms for
      replacing fossil fuels with contemporary primary production as a renewable source
      of energy. Algae can produce many times more biomass per unit area than
      terrestrial crop plants, easing the competing demands for land with food crops
      and native ecosystems. However, several aspects of algal biology present unique
      challenges to the industrial-scale aquaculture of photosynthetic microorganisms.
      These include high susceptibility to invading aquatic consumers and weeds, as
      well as prodigious requirements for nutrients that may compete with the
      fertiliser demands of other crops. Most research on algal biofuel technologies
      approaches these problems from a cellular or genetic perspective, attempting
      either to engineer or select algal strains with particular traits. However,
      inherent functional trade-offs may limit the capacity of genetic selection or
      synthetic biology to simultaneously optimise multiple functional traits for
      biofuel productivity and resilience. We argue that a community engineering
      approach that manages microalgal diversity, species composition and environmental
      conditions may lead to more robust and productive biofuel ecosystems. We review
      evidence for trade-offs, challenges and opportunities in algal biofuel
      cultivation with a goal of guiding research towards intensifying bioenergy
      production using established principles of community and ecosystem ecology. 

PMID- 24015820
TI  - Polypropylene/glass fiber hierarchical composites incorporating inorganic
      fullerene-like nanoparticles for advanced technological applications.
AB  - Novel isotactic polypropylene (iPP)/glass fiber (GF) laminates reinforced with
      inorganic fullerene-like tungsten disulfide (IF-WS2) nanoparticles as
      environmentally friendly fillers have been successfully fabricated by simple melt
      blending and fiber impregnation in a hot-press without the addition of any
      compatibilizer. The influence of IF-WS2 concentration on the morphology,
      viscosity. and thermal and mechanical behavior of the hierarchical composites has
      been investigated. Results revealed an unprecedented 62  degrees C increase in
      the degradation temperature of iPP/GF upon addition of only 4.0 wt % IF-WS2. The
      coexistence of both micro- and nanoscale fillers resulted in synergistic effects
      on enhancing the stiffness, strength, crystallinity, thermal stability, glass
      transition (Tg) and heat distortion temperature (HDT) of the matrix. The approach
      used in this work is an efficient, versatile, scalable and economic strategy to
      improve the mechanical and thermal behavior of GF-reinforced thermoplastics with
      a view to extend their use in advanced technological applications. This new type
      of composite materials shows great potential to improve the efficiency and
      sustainability of many forms of transport. 

PMID- 24015821
TI  - Identification of the pregnant woman who is using drugs: implications for
      perinatal and neonatal care.
AB  - Neonatal abstinence syndrome (NAS) is a set of drug withdrawal symptoms that
      affect the central nervous, gastrointestinal, and respiratory systems in the
      newborn when separated from the placenta at birth. Maternal substance use of
      opioids, benzodiazepines, barbiturates, and alcohol can cause NAS. Universal drug
      screening via questioning pregnant women is recommended, but identification of
      drug use is incomplete with this method. This article provides resources for the
      identification and management of drug use during pregnancy for midwives who
      provide care not only during the prenatal period but also during the intrapartum
      and postpartum periods. The impact of drug use on newborns can be significant and
      may require pharmacologic assistance with the transition to extrauterine life.
      Challenges involved in caring for the woman who is using drugs during pregnancy
      include ordering toxicology screens on the newborn, alerting social services, and
      educating the woman about her newborn's progress. Several measures to comfort a
      newborn with NAS may help to enable a mother to provide the best care for her
      newborn. 

PMID- 24015823
TI  - Preparation of pyrazine carboxamides: a reaction involving N-heterocyclic carbene
      (NHC) intermediates.
AB  - In the reactions of 2,3-pyrazinedicarboxylic anhydride with amines and anilines,
      pyrazine carboxamides are formed in good to excellent yields. A mechanism is
      proposed involving ring opening of the anhydride and decarboxylation of the
      heterocyclic ring. Based on other similar heterocyclic decarboxylations, this
      suggests the involvement of an N-heterocyclic carbene intermediate leading to the
      product. 

PMID- 24015822
TI  - PD-L1 enhances CNS inflammation and infarct volume following experimental stroke
      in mice in opposition to PD-1.
AB  - BACKGROUND: Stroke severity is worsened by recruitment of inflammatory immune
      cells into the brain. This process depends in part on T cell activation, in which
      the B7 family of co-stimulatory molecules plays a pivotal role. Previous studies
      demonstrated more severe infarcts in mice lacking programmed death-1 (PD-1), a
      member of the B7 family, thus implicating PD-1 as a key factor in limiting stroke
      severity. The purpose of this study was to determine if this protective effect of
      PD-1 involves either of its ligands, PD-L1 or PD-L2. METHODS: Central nervous
      system (CNS) inflammation and infarct volume were evaluated in male PD-L1 and PD
      L2 knockout (-/-) mice undergoing 60 minutes of middle cerebral artery occlusion
      (MCAO) followed by 96 hours of reperfusion and compared to wild-type (WT)
      C57BL/6J mice. RESULTS: PD-L1-/- and PD-L2-/- mice had smaller total infarct
      volumes compared to WT mice. The PD-L1-/- and to a lesser extent PD-L2-/- mice
      had reduced levels of proinflammatory activated microglia and/or infiltrating
      monocytes and CD4+ T cells in the ischemic hemispheres. There was a reduction in
      ischemia-related splenic atrophy accompanied by lower activation status of
      splenic T cells and monocytes in the absence of PD-L1, suggesting a pathogenic
      rather than a regulatory role for both PD-1 ligands (PD-Ls). Suppressor T cells
      (IL-10-producing CD8+CD122+ T cells) trafficked to the brain in PD-L1-/- mice and
      there was decreased expression of CD80 on splenic antigen-presenting cells (APCs)
      as compared to the WT and PD-L2-/- mice. CONCLUSIONS: Our novel observations are
      the first to implicate PD-L1 involvement in worsening outcome of experimental
      stroke. The presence of suppressor T cells in the right MCAO-inflicted hemisphere
      in mice lacking PD-L1 implicates these cells as possible key contributors for
      controlling adverse effects of ischemia. Increased expression of CD80 on APCs in
      WT and PD-L2-/- mice suggests an overriding interaction leading to T cell
      activation. Conversely, low CD80 expression by APCs, along with increased PD-1
      and PD-L2 expression in PD-L1-/- mice suggests alternative T cell signaling
      pathways, leading to a suppressor phenotype. These results suggest that agents
      (for example antibodies) that can target and neutralize PD-L1/2 may have
      therapeutic potential for treatment of human stroke.

PMID- 24015824
TI  - Influence of chirality on vibrational and relaxational properties of (S)- and
      (R,S)-ibuprofen/methyl-beta-cyclodextrin inclusion complexes: an INS and QENS
      study.
AB  - In this paper, we analyze the internal picosecond dynamics of enantiomeric ((S)-)
      and racemic ((R,S)-) ibuprofen (IBP), when forming inclusion complexes, in solid
      state, with methyl-beta-cyclodextrin (Me-beta-CD), by inelastic and quasi elastic
      neutron scattering. The study was aimed at understanding, by the analysis of the
      vibrational and relaxational properties of the inclusion complexes also with
      respect to the single components, if and how the differences in the structural
      properties of the hydrogen bond (HB) network of (S)- and (R,S)-IBP can have
      influence on the complexation process triggered by "host-guest" interactions,
      whose detailed knowledge is retained as a prerequisite for enantiodiscrimination.
      From the results, a similar complexation mechanism for (S)- and (R,S)-IBP is
      argued, with a preferred penetration mode involving the isopropyl group of IBP. 

PMID- 24015825
TI  - Comparison of synthetic dopamine-eumelanin formed in the presence of oxygen and
      Cu2+ cations as oxidants.
AB  - Eumelanin is not only a ubiquitous pigment among living organisms with
      photoprotective and antioxidant functions, but is also the subject of intense
      interest in materials science due to its photoconductivity and as a possible
      universal coating platform, known as "polydopamine films". The structure of
      eumelanin remains largely elusive, relying either on a polymeric model or on a
      heterogeneous aggregate structure. The structure of eumelanin as well as that of
      the closely related "polydopamine films" can be modified by playing on the nature
      of the oxidant used to oxidize dopamine or related compounds. In this
      investigation, we show that dopamine-eumelanins produced from dopamine in the
      presence of either air (O2 being the oxidant) or Cu(2+) cations display
      drastically different optical and colloidal properties in relation with a
      different supramolecular assembly of the oligomers of 5,6 dihydroxyindole, the
      final oxidation product of dopamine. The possible origin of these differences is
      discussed on the basis of Cu(2+) incorporation in Cu dopamine-eumelanin. 

PMID- 24015826
TI  - Cardiac arrest after intravenous calcium administration for calcitonin
      stimulation test.

PMID- 24015827
TI  - Episodic memory and episodic future thinking impairments in high-functioning
      autism spectrum disorder: an underlying difficulty with scene construction or
      self-projection?
AB  - OBJECTIVE: There appears to be a common network of brain regions that underlie
      the ability to recall past personal experiences (episodic memory) and the ability
      to imagine possible future personal experiences (episodic future thinking). At
      the cognitive level, these abilities are thought to rely on "scene construction"
      (the ability to bind together multimodal elements of a scene in mind--dependent
      on hippocampal functioning) and temporal "self-projection" (the ability to
      mentally project oneself through time--dependent on prefrontal cortex
      functioning). Although autism spectrum disorder (ASD) is characterized by
      diminished episodic memory, it is unclear whether episodic future thinking is
      correspondingly impaired. Moreover, the underlying basis of such impairments
      (difficulties with scene construction, self-projection, or both) is yet to be
      established. The current study therefore aimed to elucidate these issues. METHOD:
      Twenty-seven intellectually high-functioning adults with ASD and 29 age- and IQ
      matched neurotypical comparison adults were asked to describe (a) imagined
      atemporal, non-self-relevant fictitious scenes (assessing scene construction),
      (b) imagined plausible self-relevant future episodes (assessing episodic future
      thinking), and (c) recalled personally experienced past episodes (assessing
      episodic memory). Tests of narrative ability and theory of mind were also
      completed. RESULTS: Performances of participants with ASD were significantly and
      equally diminished in each condition and, crucially, this diminution was
      independent of general narrative ability. CONCLUSIONS: Given that participants
      with ASD were impaired in the fictitious scene condition, which does not involve
      self-projection, we suggest the underlying difficulty with episodic memory/future
      thinking is one of scene construction.

PMID- 24015828
TI  - Prospective memory deficits in illicit polydrug users are associated with the
      average long-term typical dose of ecstasy typically consumed in a single session.
AB  - RATIONALE: Neuroimaging evidence suggests that ecstasy-related reductions in SERT
      densities relate more closely to the number of tablets typically consumed per
      session rather than estimated total lifetime use. To better understand the basis
      of drug related deficits in prospective memory (p.m.) we explored the association
      between p.m. and average long-term typical dose and long-term frequency of use.
      METHOD: Study 1: Sixty-five ecstasy/polydrug users and 85 nonecstasy users
      completed an event-based, a short-term and a long-term time-based p.m. task.
      Study 2: Study 1 data were merged with outcomes on the same p.m. measures from a
      previous study creating a combined sample of 103 ecstasy/polydrug users, 38
      cannabis-only users, and 65 nonusers of illicit drugs. RESULTS: Study 1:
      Ecstasy/polydrug users had significant impairments on all p.m. outcomes compared
      with nonecstasy users. Study 2: Ecstasy/polydrug users were impaired in event
      based p.m. compared with both other groups and in long-term time-based p.m.
      compared with nonillicit drug users. Both drug using groups did worse on the
      short-term time-based p.m. task compared with nonusers. Higher long-term average
      typical dose of ecstasy was associated with poorer performance on the event and
      short-term time-based p.m. tasks and accounted for unique variance in the two
      p.m. measures over and above the variance associated with cannabis and cocaine
      use. CONCLUSIONS: The typical ecstasy dose consumed in a single session is an
      important predictor of p.m. impairments with higher doses reflecting increasing
      tolerance giving rise to greater p.m. impairment.

PMID- 24015829
TI  - Talk or text to tell? How young adults in Canada and South Africa prefer to
      receive STI results, counseling, and treatment updates in a wireless world.
AB  - Young adults often lack access to confidential, long-lasting, and nonjudgmental
      interactions with sexual health professionals at brick-and-mortar clinics. To
      ensure that patients return for their STI test results, post-result counseling,
      and STI-related information, computer-mediated health intervention programming
      allows them to receive sexual health information through onsite computers, the
      Internet, and mobile phone calls and text messages. To determine whether young
      adults (age: M = 21 years) prefer to communicate with health professionals about
      the status of their sexual health through computer-mediated communication
      devices, 303 second-year university students (183 from an urban North American
      university and 120 from a periurban university in South Africa) completed a paper
      based survey indicating how they prefer to communicate with doctors and nurses:
      talking face to face, mobile phone call, text message, Internet chat programs,
      Facebook, Twitter, or e-mail. Nearly all students, and female students in South
      Africa in particular, prefer to receive their STI test results, post-results
      counseling, and STI-related information by talking face to face with doctors and
      nurses rather than communicating through computers or mobile phones. Results are
      clarified in relation to gender, availability of various technologies, and
      prevalence of HIV in Canada and in South Africa. 

PMID- 24015830
TI  - Techniques of electroanatomic mapping and catheter ablation of atrial
      tachyarrhythmias with a recipient to donor atria conduction. Reply to letter.

PMID- 24015831
TI  - Regulated DNA rearrangement during sporulation in Bacillus weihenstephanensis
      KBAB4.
AB  - Temperate phages can integrate their genomes into a specific region of a host
      chromosome to produce lysogens (prophage). During genome insertion, prophages may
      interrupt the gene coding sequence. In Bacillus subtilis, the sigma factor gene
      sigK is interrupted by a 48 kb prophage-like element. sigK is a composite coding
      sequence from two partial genes during sporulation. For over two decades,
      however, no further examples of DNA element-mediated gene reconstitution other
      than sigK have been identified in spore formers. Here we report that the gene for
      dipicolinic acid (DPA) synthetase beta subunit spoVFB in B. weihenstephanensis
      KBAB4 is interrupted by a prophage-like element named vfbin. DPA is synthesized
      in the mother cell and required for maintaining spore dormancy. We found that
      spoVFB was a composite coding sequence generated in the mother cell via
      chromosomal rearrangement that excised vfbin. Furthermore, vfbin caused excision
      after phage-inducer treatment, but vfbin appeared to be defective as a prophage.
      We also found various spore-forming bacteria in which sporulation-related genes
      were disrupted by prophage-like DNA elements. These results demonstrate the first
      example of a similar mechanism that affects a sporulation gene other than sigK
      and suggest that this prophage-mediated DNA rearrangement is a common phenomenon
      in spore-forming bacteria. 

PMID- 24015832
TI  - Host-specific Nod-factors associated with Medicago truncatula nodule infection
      differentially induce calcium influx and calcium spiking in root hairs.
AB  - Rhizobial nodulation (Nod) factors activate both nodule morphogenesis and
      infection thread development during legume nodulation. Nod factors induce two
      different calcium responses: intra-nuclear calcium oscillations and a calcium
      influx at the root hair tip. Calcium oscillations activate nodule development; we
      wanted to test if the calcium influx is associated with infection. Sinorhizobium
      meliloti nodL and nodF mutations additively reduce infection of Medicago
      truncatula. Nod-factors made by the nodL mutant lack an acetyl group; mutation of
      nodF causes the nitrogen (N)-linked C16:2 acyl chain to be replaced by C18:1. We
      tested whether these Nod-factors differentially induced calcium influx and
      calcium spiking. The absence of the NodL-determined acetyl group greatly reduced
      the induction of calcium influx without affecting calcium spiking. The calcium
      influx was even further reduced if the N-linked C16:2 acyl group was replaced by
      C18:1. These additive effects on calcium influx correlate with the additive
      effects of mutations in nodF and nodL on legume infection. Infection thread
      development is inhibited by ethylene, which also inhibited Nod-factor-induced
      calcium influx. We conclude that Nod-factor perception differentially activates
      the two developmental pathways required for nodulation and that activation of the
      pathway involving the calcium influx is important for efficient infection. 

PMID- 24015834
TI  - Photo-onycholysis caused by an unusual beach game activity: a pediatric case of a
      side effect caused by doxycycline.
AB  - Photo-onycholysis caused by doxycycline has rarely been reported in children. We
      present the case of a boy who loved to play pinball while at the beach, holding
      tightly to the machine. He developed a photo-onycholysis predominantly on his
      thumbs while he was being treated with 20 mg/day of doxycycline, a low dose but
      enough to trigger the photoreaction. 

PMID- 24015833
TI  - Parental food-related behaviors and family meal frequencies: associations in
      Norwegian dyads of parents and preadolescent children.
AB  - BACKGROUND: Frequent family meals are associated with healthy dietary behaviors
      and other desirable outcomes in children and adolescents. Therefore, increased
      knowledge about factors that may increase the occurrence of family meals is
      warranted. The present study has its focus on the home food environment, and aims
      to explore potential associations between parent-reported feeding behaviors and
      child-reported family meal frequencies. METHODS: Cross-sectional surveys were
      performed among 10-12-year-olds and their parents recruited from eighteen schools
      in southwest Norway. The child questionnaire included measures of family meal
      frequencies (breakfast, dinner and supper). The parent questionnaire included
      measures of parental feeding behaviors adapted from the Comprehensive Feeding
      Practices Questionnaire. A series of multiple linear regression analyses were
      conducted to examine the relationships between parental feeding behaviors and the
      frequency of family meals. RESULTS: The frequency of family breakfasts was
      associated with three parental feeding variables; home environment (beta=.11,
      p<.05), pressure to eat (beta=.11, p<.01), and monitoring (beta=.10, p<.05). The
      frequency of family dinners and suppers was associated with one parental feeding
      variable; home environment (beta=.11, p<.01 and beta=.12, p<.01 for dinners and
      suppers respectively). CONCLUSIONS: The home environment variable was the most
      important correlate of child-reported family meal frequencies in this study.
      Although further research is needed, our findings support the evident influence
      of parents and the home food environment on child and adolescent eating behavior,
      which in the present study was measured as the frequency of shared family meals.

PMID- 24015835
TI  - Optimizing the energy efficiency of capacitive deionization reactors working
      under real-world conditions.
AB  - Capacitive deionization (CDI) is a rapidly emerging desalination technology that
      promises to deliver clean water while storing energy in the electrical double
      layer (EDL) near a charged surface in a capacitive format. Whereas most research
      in this subject area has been devoted to using CDI for removing salts, little
      attention has been paid to the energy storage aspect of the technology. However,
      it is energy storage that would allow this technology to compete with other
      desalination processes if this energy could be stored and reused efficiently.
      This requires that the operational aspects of CDI be optimized with respect to
      energy used both during the removal of ions as well as during the regeneration
      cycle. This translates into the fact that currents applied during deionization
      (charging the EDL) will be different from those used in regeneration (discharge).
      This paper provides a mechanistic analysis of CDI in terms of energy consumption
      and energy efficiencies during the charging and discharging of the system under
      several scenarios. In a previous study, we proposed an operational buffer mode in
      which an effective separation of deionization and regeneration steps would allow
      one to better define the energy balance of this CDI process. This paper reports
      on using this concept, for optimizing energy efficiency, as well as to improve
      upon the electro-adsorption of ions and system lifetime. Results obtained
      indicate that real-world operational modes of running CDI systems promote the
      development of new and unexpected behavior not previously found, mainly
      associated with the inhomogeneous distribution of ions across the structure of
      the electrodes. 

PMID- 24015837
TI  - Highly sensitive detection of caspase-3 activities via a nonconjugated gold
      nanoparticle-quantum dot pair mediated by an inner-filter effect.
AB  - We describe here a simple fluorometric assay for the highly sensitive detection
      of caspase-3 activities on the basis of the inner-filter effect of gold
      nanoparticles (AuNPs) on CdTe quantum dots (QDs). The method takes advantage of
      the high molar absorptivity of the plasmon band of gold nanoparticles as well as
      the large absorption band shift from 520 to 680 nm upon nanoparticle aggregation.
      When labeled with a peptide possessing the caspase-3 cleavage sequence (DEVD),
      the monodispersed Au-Ps (peptide-modified AuNPs) exhibited a tendency to
      aggregate when exposed to caspase-3, which induced the absorption band transition
      from 520 to 680 nm and turned on the fluorescence of the CdTe QDs for caspase-3
      sensing. Under optimum conditions, a high sensitivity towards caspase-3 was
      achieved with a detection limit as low as 18 pM, which was much lower than the
      corresponding assays based on absorbance or other approaches. Overall, we
      demonstrated a facile and sensitive approach for caspase-3 detection, and we
      expected that this method could be potentially generalized to design more
      fluorescent assays for sensing other bioactive entities. 

PMID- 24015838
TI  - Relationship between hunger, adherence to antiretroviral therapy and plasma HIV
      RNA suppression among HIV-positive illicit drug users in a Canadian setting.
AB  - Food insecurity may be a barrier to achieving optimal HIV treatment-related
      outcomes among illicit drug users. This study therefore, aimed to assess the
      impact of severe food insecurity, or hunger, on plasma HIV RNA suppression among
      illicit drug users receiving antiretroviral therapy (ART). A cross-sectional
      Multivariate logistic regression model was used to assess the potential
      relationship between hunger and plasma HIV RNA suppression. A sample of n = 406
      adults was derived from a community-recruited open prospective cohort of HIV
      positive illicit drug users, in Vancouver, British Columbia (BC), Canada. A total
      of 235 (63.7%) reported "being hungry and unable to afford enough food," and 241
      (59.4%) had plasma HIV RNA < 50 copies/ml. In unadjusted analyses, self-reported
      hunger was associated with lower odds of plasma HIV RNA suppression (Odds Ratio =
      0.59, 95% confidence interval [CI]: 0.39-0.90, p = 0.015). In multivariate
      analyses, this association was no longer significant after controlling for socio
      demographic, behavioral, and clinical characteristics, including 95% adherence
      (Adjusted Odds Ratio [AOR] = 0.65, 95% CI: 0.37-1.10, p = 0.105). Multivariate
      models stratified by 95% adherence found that the direction and magnitude of this
      association was not significantly altered by the adherence level. Hunger was
      common among illicit drug users in this setting. Although, there was an
      association between hunger and lower likelihood of plasma HIV RNA suppression,
      this did not persist in adjusted analyses. Further research is warranted to
      understand the social-structural, policy, and physical factors shaping the HIV
      outcomes of illicit drug users. 

PMID- 24015839
TI  - Temporally controlled targeting of 4-hydroxynonenal to specific proteins in
      living cells.
AB  - In-depth chemical understanding of complex biological processes hinges upon the
      ability to systematically perturb individual systems. However, current approaches
      to study impacts of biologically relevant reactive small molecules involve
      bathing of the entire cell or isolated organelle with excess amounts, leading to
      off-target effects. The resultant lack of biochemical specificity has plagued our
      understanding of how biological electrophiles mediate signal transduction or
      regulate responses that confer defense mechanisms to cellular electrophilic
      stress. Here we introduce a target-specific electrophile delivery platform that
      will ultimately pave the way to interrogate effects of reactive electrophiles on
      specific target proteins in cells. The new methodology is demonstrated by
      photoinducible targeted delivery of 4-hydroxynonenal (HNE) to the proteins Keap1
      and PTEN. Covalent conjugation of the HNE-precursor to HaloTag fused to the
      target proteins enables directed HNE delivery upon photoactivation. The strategy
      provides proof of concept of selective delivery of reactive electrophiles to
      individual electrophile-responsive proteins in mammalian cells. It opens a new
      avenue enabling more precise determination of the pathophysiological consequences
      of HNE-induced chemical modifications on specific target proteins in cells. 

PMID- 24015840
TI  - New Opportunities for Birth Centers in a Transforming Health Care System.

PMID- 24015841
TI  - Phase I study of GTI-2040, a ribonucleotide reductase antisense, with high dose
      cytarabine in patients with relapsed/refractory acute myeloid leukemia.
AB  - We hypothesized that GTI-2040, a 20-mer oligonucleotide complementary to the R2
      subunit mRNA of ribonucleotide reductase, combined with high dose cytarabine
      (HiDAC) would result in enhanced cytotoxicity by favoring Ara-CTP DNA
      incorporation. In a phase I dose escalation trial, adults (>= 60 years) with
      refractory or relapsed acute myeloid leukemia (AML) received daily HiDAC plus
      infusional GTI-2040. Using a novel assay, evidence of intracellular drug
      accumulation and target R2 down-regulation was observed. GTI-2040/HiDAC can be
      administered safely. However, with no complete remissions observed, alternative
      doses and schedules may need to be investigated to achieve clinical activity in
      older patients with AML.

PMID- 24015842
TI  - Genetic risk of chronic lymphocytic leukemia: a tale of two cities.

PMID- 24015843
TI  - Elimination of the coffee-ring effect by promoting particle adsorption and long
      range interaction.
AB  - A Monte Carlo model has been developed to investigate the transition from the
      coffee-ring deposition to the uniform coverage in drying pinned sessile colloidal
      droplets. The model applies the diffusion-limited aggregation (DLA) approach
      coupled with the biased random walk (BRW) to simulate the particle migration and
      agglomeration during the droplet drying process. It is shown that the
      simultaneous presence of the particle adsorption, long-range attraction, and
      circulatory motion processes is important for the transition from the coffee-ring
      effect to the uniform deposition of finally dried particles. The absence of one
      of the specified factors favors the coffee-ring deposition near the droplet
      boundary. The strong outward capillary flow on the latest evaporation stage can
      easily destroy the entire particle pre-ordering at the early drying stages. The
      formation of a robust particle structure is required to resist the outward flow
      and alter the coffee-ring effect. 

PMID- 24015844
TI  - Different TLR4 expression and microglia/macrophage activation induced by
      hemorrhage in the rat spinal cord after compressive injury.
AB  - BACKGROUND: Hemorrhage is a direct consequence of traumatic injury to the central
      nervous system and may cause innate immune reactions including cerebral Toll-like
      receptor (TLR) 4 upregulation which usually leads to poor outcome in the
      traumatic brain injury. In spinal cord injury (SCI), however, how hemorrhage
      induces innate immune reaction in spinal parenchyma remains unknown. The present
      study aimed to see whether blood component and/or other factor(s) induce TLR4 and
      microglia/macrophages involved innate immune reactions in the rat spinal cord
      after traumatic injury. METHODS: Using the compressive SCI model of the rat,
      hemorrhage in the spinal cord was identified by hematoxylin-eosin staining.
      Microglia/macrophage activation, TLR4 expression, and cell apoptosis were
      investigated by immunohistochemistry. Nuclear factor (NF)-kappaB p50 level of the
      two segments of the cord was detected by western blotting assay. With carbon
      powder injection, blood origination of the hematoma was explored. The blood
      spinal cord barrier (BSCB) states of the lesion site and the hematoma were
      compared with immunohistochemistry and tannic acid-ferric chloride staining.
      RESULTS: Histological observation found blood accumulated in the center of
      compression lesion site (epicenter) and in the hematoma approximately 1.5 cm away
      from the epicenter. TLR4 expression, microglia//macrophage activation, and
      subsequent apoptosis in the area of far-away hematoma were late and weak in
      comparison to that in epicenter. In addition, TLR4 positive microglia/macrophages
      appeared to be phagocytotic in the far-away hematoma more obviously than that in
      the epicenter. Injected carbon powder indicated that accumulated blood of the far
      away hematoma originated from the bleeding of the lesion epicenter, and the BSCB
      around the hematoma was not compromised in the early phase. Accordingly, at 3
      days post injury, NF-kappaB p50 was upregulated based on the similar levels of
      blood component hemoglobin, and cell apoptosis was obvious in the epicenter but
      not in the far-away hematoma. CONCLUSION: These data suggest that besides blood
      component, BSCB compromise and the extent of tissue injury contribute more to
      TLR4 and microglia/macrophage responses to the spinal cord hemorrhage. Therefore,
      the innate immune environment is a necessary consideration for the SCI therapy
      targeting TLR4 and microglia/macrophages.

PMID- 24015845
TI  - Iron-catalyzed one-pot 2,3-diarylquinazolinone formation from 2-nitrobenzamides
      and alcohols.
AB  - A novel approach for the synthesis of 2,3-diarylquinazolinones using iron as
      catalyst is described. Various 2-nitro-N-arylbenzamides reacted with benzylic
      alcohols to selectively give the corresponding products in the absence of
      external oxidant or reductant. 

PMID- 24015846
TI  - Medical Inpatients' Use of Information Technology: Characterizing the Potential
      to Share Information Electronically.
AB  - Hospitalized patients frequently have an incomplete understanding of important
      aspects of their care. Patient-facing technologies, increasingly used in
      outpatient settings to exchange information between patient and provider, may
      have utility in the hospital setting. We conducted structured interviews of
      hospitalized medical patients to assess current use of information technology,
      gauge interest in receiving information electronically, and prioritize potential
      content options. Overall, 150 of 175 (86%) eligible patients completed
      interviews. A majority (69%) of patients used the Internet prior to hospital
      admission. One third (32%) of patients had used the Internet during their
      hospitalization with half of those reporting use for health information. Overall,
      nearly half (42%) reported interest in receiving health information
      electronically during hospitalization and a majority (59%) were interested in
      receiving health information electronically after hospitalization. Patients
      expressed high interest in receiving information to help them learn more about
      diagnoses and treatments, medication lists, lists of planned tests, and summaries
      of completed tests and procedures. Many general medical patients are interested
      in receiving health information electronically from hospital providers. Our
      findings support the development of hospital-based patient-facing health
      information technologies and prioritize content options patients find most
      beneficial. 

PMID- 24015847
TI  - Effects of maternal hypothyroidism on offspring hippocampus and memory.
AB  - BACKGROUND: Rodents with gestational thyroid-hormone (TH) deficiencies and
      children with congenital hypothyroidism show abnormal hippocampal development.
      Given that the human hippocampus starts to develop early in gestation, we asked
      if children born to women with hypothyroidism during pregnancy also show
      hippocampal abnormalities and if this is related to the severity of maternal TH
      insufficiency and current memory functioning. We additionally sought to determine
      whether effects were more prominent in anterior or posterior hippocampal
      subsections given these support different memory functions and have different
      developmental trajectories. We hypothesized that these children would have
      smaller than normal hippocampal volumes than controls and show memory deficits on
      both standardized tests and indices of "everyday" memory functioning. METHODS: We
      studied 54 children aged 9 to 12 years: 30 controls and 24 HYPO cases-offspring
      from women diagnosed with hypothyroidism prior to or during pregnancy and treated
      with l-thyroxine. All children received a thorough assessment of memory functions
      and an MRI scan. For each child, right and left hippocampi were manually traced,
      and volumes of right and left hippocampi and anterior and posterior segments were
      determined. RESULTS: HYPO cases showed significantly smaller right and left
      hippocampal volumes than controls, particularly in right posterior and left
      anterior segments. In HYPO children, hippocampal volumes were negatively
      correlated with maternal third-trimester TSH levels and positively correlated
      with third-trimester fT4. HYPO cases scored significantly below controls on one
      objective and several subjective memory indices, and these were correlated with
      hippocampal volumes. CONCLUSION: Early TH insufficiency from maternal
      hypothyroidism affects offspring hippocampal development and memory.

PMID- 24015848
TI  - Fragment-based design for the development of N-domain-selective angiotensin-1
      converting enzyme inhibitors.
AB  - ACE (angiotensin-1-converting enzyme) is a zinc metallopeptidase that plays a
      prominent role in blood pressure regulation and electrolyte homeostasis. ACE
      consists of two homologous domains that despite similarities of sequence and
      topology display differences in substrate processing and inhibitor binding. The
      design of inhibitors that selectively inhibit the N-domain (N-selective) could be
      useful in treating conditions of tissue injury and fibrosis due to build-up of N
      domain-specific substrate Ac-SDKP (N-acetyl-Ser-Asp-Lys-Pro). Using a receptor
      based SHOP (scaffold hopping) approach with N-selective inhibitor RXP407, a
      shortlist of scaffolds that consisted of modified RXP407 backbones with novel
      chemotypes was generated. These scaffolds were selected on the basis of enhanced
      predicted interaction energies with N-domain residues that differed from their C
      domain counterparts. One scaffold was synthesized and inhibitory binding tested
      using a fluorogenic ACE assay. A molecule incorporating a tetrazole moiety in the
      P2 position (compound 33RE) displayed potent inhibition (K(i)=11.21+/-0.74 nM)
      and was 927-fold more selective for the N-domain than the C-domain. A crystal
      structure of compound 33RE in complex with the N-domain revealed its mode of
      binding through aromatic stacking with His388 and a direct hydrogen bond with the
      hydroxy group of the N-domain specific Tyr369. This work further elucidates the
      molecular basis for N-domain-selective inhibition and assists in the design of
      novel N-selective ACE inhibitors that could be employed in treatment of fibrosis
      disorders.

PMID- 24015850
TI  - Stability of the K4b2 portable metabolic analyser during rest, walking and
      running.
AB  - This study investigated the stability of the measurement of respiratory variables
      during rest, walking and running using the K4b(2) portable metabolic analyser in
      ten active males (age 31 +/- 11 years; VO2 peak 42.1 +/- 2.6 ml . min(-1) . kg(
      1)). Following a 10 min rest, participants completed three discontinuous
      incremental exercise tests on a treadmill while walking (4, 5 and 6 km . h(-1))
      and running (8, 10, 12, 14 and 16 km . h(-1), or until volitional exhaustion).
      Participants completed 3 min of exercise at each speed, followed by a 3 min
      recovery after each stage above 10 km . h(-1). The respiratory variables were
      measured using either a laboratory-based metabolic cart as a reference method
      (Oxycon Pro, OP), a K4b(2) calibrated immediately before the test (K4b(2)), or a
      K4b(2) calibrated 1 h before the test (K4b(2)DEL). Compared to the OP, carbon
      dioxide production (VCO2) and V(E) were not different when measured by K4b(2) or
      K4b(2)DEL. There was no difference in VO2 between OP and K4b(2) tests (P = 0.19,
      mean difference = 38 ml . min(-1) and limits of agreement (LOA) = 208 to -285)
      although K4b(2)DEL overestimated VO2 (P = 0.05, mean difference = 84 ml . min(-1)
      and LOA = 302 to -469). These data suggest that a drift in measurement accuracy
      appears to cause the K4b(2) to overestimate VO2 in tests lasting longer than 1 h.

PMID- 24015849
TI  - RNA-seq analyses of gene expression in the microsclerotia of Verticillium
      dahliae.
AB  - BACKGROUND: The soilborne fungus, Verticillium dahliae, causes Verticillium wilt
      disease in plants. Verticillium wilt is difficult to control since V. dahliae is
      capable of persisting in the soil for 10 to 15 years as melanized microsclerotia,
      rendering crop rotation strategies for disease control ineffective.
      Microsclerotia of V. dahliae overwinter and germinate to produce infectious
      hyphae that give rise to primary infections. Consequently, microsclerotia
      formation, maintenance, and germination are critically important processes in the
      disease cycle of V. dahliae. RESULTS: To shed additional light on the molecular
      processes that contribute to microsclerotia biogenesis and melanin synthesis in
      V. dahliae, three replicate RNA-seq libraries were prepared from 10 day-old
      microsclerotia (MS)-producing cultures of V. dahliae, strain VdLs.17 (average =
      52.23 million reads), and those not producing microsclerotia (NoMS, average =
      50.58 million reads). Analyses of these libraries for differential gene
      expression revealed over 200 differentially expressed genes, including up
      regulation of melanogenesis-associated genes tetrahydroxynaphthalene reductase
      (344-fold increase) and scytalone dehydratase (231-fold increase), and additional
      genes located in a 48.8 kilobase melanin biosynthetic gene cluster of strain
      VdLs.17. Nearly 50% of the genes identified as differentially expressed in the MS
      library encode hypothetical proteins. Additional comparative analyses of gene
      expression in V. dahliae, under growth conditions that promote or preclude
      microsclerotial development, were conducted using a microarray approach with RNA
      derived from V. dahliae strain Dvd-T5, and from the amicrosclerotial vdh1 strain.
      Differential expression of selected genes observed by RNA-seq or microarray
      analysis was confirmed using RT-qPCR or Northern hybridizations. CONCLUSION:
      Collectively, the data acquired from these investigations provide additional
      insight into gene expression and molecular processes that occur during MS
      biogenesis and maturation in V. dahliae. The identified gene products could
      therefore potentially represent new targets for disease control through
      prevention of survival structure development.

PMID- 24015851
TI  - Novel photo-sulfite system: toward simultaneous transformations of inorganic and
      organic pollutants.
AB  - An efficient and green advanced oxidation process (i.e., photo-sulfite reaction)
      for the simultaneous oxidation of sulfite and organic pollutants in water is
      reported. The photo-sulfite system (UV-Fe(III)-sulfite) is based on the Fe
      catalyzed sulfite oxidation and photochemistry of Fe(III) species. SO4(*-) and
      (*)OH radicals were identified in the photo-sulfite system with radical
      scavenging experiments using specific alcohols. This novel technology was
      consistently proven to be more favorable than the alternative Fe(III)-sulfite
      systems for the degradation of 2,4,6-trichlorophenol (2,4,6-TCP) and other
      organic pollutants at all conditions tested. The reactivity of photo-sulfite
      system was sustained due to the spontaneous switch of photoactive species from
      Fe(III)-sulfito to Fe(III)-hydroxo complexes with the depletion of sulfite and
      the decrease in pH. In contrast, in the absence of light the performance of the
      Fe(III)-sulfite system was greatly diminished after the consumption of sulfite.
      The formation of the Fe(III)-sulfito complex is a necessary step for initiating
      the photo-sulfite reaction. Inhibition of the oxidation of 2,4,6-TCP and methyl
      orange (MO) was observed in the presence of ligands that can stabilize one or
      more of the reactants: Fe(III), Fe(II), or sulfite. Our study provides a new
      facile route for the generation of SO4(*-) and simultaneous removal of organic
      and inorganic pollutants. 

PMID- 24015852
TI  - The co-evolution of social institutions, demography, and large-scale human
      cooperation.
AB  - Human cooperation is typically coordinated by institutions, which determine the
      outcome structure of the social interactions individuals engage in. Explaining
      the Neolithic transition from small- to large-scale societies involves
      understanding how these institutions co-evolve with demography. We study this
      using a demographically explicit model of institution formation in a patch
      structured population. Each patch supports both social and asocial niches. Social
      individuals create an institution, at a cost to themselves, by negotiating how
      much of the costly public good provided by cooperators is invested into
      sanctioning defectors. The remainder of their public good is invested in
      technology that increases carrying capacity, such as irrigation systems. We show
      that social individuals can invade a population of asocials, and form
      institutions that support high levels of cooperation. We then demonstrate
      conditions where the co-evolution of cooperation, institutions, and demographic
      carrying capacity creates a transition from small- to large-scale social groups.

PMID- 24015853
TI  - In situ genetic association for serotiny, a fire-related trait, in Mediterranean
      maritime pine (Pinus pinaster).
AB  - Wildfire is a major ecological driver of plant evolution. Understanding the
      genetic basis of plant adaptation to wildfire is crucial, because impending
      climate change will involve fire regime changes worldwide. We studied the
      molecular genetic basis of serotiny, a fire-related trait, in Mediterranean
      maritime pine using association genetics. A single nucleotide polymorphism (SNP)
      set was used to identify genotype : phenotype associations in situ in an
      unstructured natural population of maritime pine (eastern Iberian Peninsula)
      under a mixed-effects model framework. RR-BLUP was used to build predictive
      models for serotiny in this region. Model prediction power outside the focal
      region was tested using independent range-wide serotiny data. Seventeen SNPs were
      potentially associated with serotiny, explaining approximately 29% of the trait
      phenotypic variation in the eastern Iberian Peninsula. Similar prediction power
      was found for nearby geographical regions from the same maternal lineage, but not
      for other genetic lineages. Association genetics for ecologically relevant traits
      evaluated in situ is an attractive approach for forest trees provided that traits
      are under strong genetic control and populations are unstructured, with large
      phenotypic variability. This will help to extend the research focus to ecological
      keystone non-model species in their natural environments, where polymorphisms
      acquired their adaptive value.

PMID- 24015854
TI  - Sex differences in health care provider communication during genital herpes care
      and patients' health outcomes.
AB  - Research in primary care medicine demonstrates that health care providers'
      communication varies depending on their sex, and that these sex differences in
      communication can influence patients' health outcomes. The present study aimed to
      examine the extent to which sex differences in primary care providers'
      communication extend to the sensitive context of gynecological care for genital
      herpes and whether these potential sex differences in communication influence
      patients' herpes transmission prevention behaviors and herpes-related quality of
      life. Women (N = 123) from the United States recently diagnosed with genital
      herpes anonymously completed established measures in which they rated (a) their
      health care providers' communication, (b) their herpes transmission prevention
      behaviors, and (c) their herpes-related quality of life. The authors found
      significant sex differences in health care providers' communication; this finding
      supports that sex differences in primary care providers' communication extend to
      gynecological care for herpes. Specifically, patients with female health care
      providers indicated that their providers engaged in more patient-centered
      communication and were more satisfied with their providers' communication.
      However, health care providers' sex did not predict women's quality of life, a
      finding that suggests that health care providers' sex alone is of little
      importance in patients' health outcomes. Patient-centered communication was
      significantly associated with greater quality-of-life scores and may provide a
      promising avenue for intervention. 

PMID- 24015855
TI  - Correlation between global longitudinal strain and QRS voltage on
      electrocardiogram in patients with left ventricular hypertrophy.
AB  - PURPOSE: Left ventricular hypertrophy (LVH) is as an independent risk factor.
      Discrepancies were reported between LV mass (LVM) estimated by echocardiography
      and electrocardiography (ECG) findings. We hypothesized that QRS voltage criteria
      may reflect not only anatomical changes (LVM) but also changes in LV function and
      we tested the relationship between QRS voltage and echocardiographic parameters
      of LV function in patients (pts) with different types of LVH. METHODS: We
      prospectively enrolled pts with LVH and preserved ejection fraction (LVEF >50%):
      20 pts with isolated arterial hypertension, HTN, 20 pts with severe aortic
      stenosis, AS (indexed aortic valve area <0.6 cm(2)/m(2)), and 20 pts with
      symmetric hypertrophic cardiomyopathy, HCM. Standard 12-lead ECG (including
      Sokolow and Cornell voltage indices) and a comprehensive two-dimensional (2D)
      echocardiography were performed in all. Left ventricular mass was calculated
      according to Devereux formula. Global longitudinal strain (GLS) was assessed by
      speckle tracking echocardiography. RESULTS: A significant correlation was found
      between both ECG indices and LVM assessed by echocardiography. Moreover,
      significant correlations were found between Sokolow-Lyon voltage and LVEF (r =
      0.26; P = 0.03), GLS (r = 0.59; P < 0.001) and E/e' average (r = 0.43; P <
      0.001). Cornell voltage index correlated significantly only with GLS. In
      multivariable analysis GLS emerged as the only independent correlate of both
      Sokolow-Lyon (beta = 0.6, P < 0.001) and Cornell voltage indices (beta = 0.45, P
      < 0.001). CONCLUSION: These findings suggest that in pts with LVH, ECG should no
      longer be used only as a surrogate method for LVM estimation (structural changes
      only), but rather as an investigation complementary to imaging, incorporating
      information on overall LV remodeling (changes in structure and function).

PMID- 24015856
TI  - Participation and performance trends in 100-km ultra-marathons worldwide.
AB  - The aims of the present study were to (1) investigate the participation trends
      for the origin of athletes competing in 100-km ultra-marathons and (2) determine
      the nationalities of athletes achieving the fastest 100-km race times worldwide.
      Race times and nationality from 112,283 athletes (15,204 women and 97,079 men)
      from 102 countries who completed a 100-km ultra-marathon worldwide between 1998
      and 2011 were investigated using single- and multi-level regression analyses. The
      number of finishers increased exponentially, both for women and men. Most of the
      finishers (73.5%) were from Europe, in particular, France (30.4%). The number of
      finishers from Japan, Germany, Italy, Poland and the United States of America
      increased exponentially during the studied period. For women, runners from Canada
      became slower while those from Italy became faster over time. For men, runners
      from Belgium, Canada and Japan became slower. Between 1998 and 2011, the ten best
      race times were achieved by Japanese runners for both women with 457.1 (s = 28.8)
      min and men with 393.4 (s = 9.6) min. To summarise, most of the finishers in 100
      km ultra-marathons originated from Europe, but the best performances belong to
      Japanese runners. Although East African runners dominate running up to a
      marathon, Japanese were the best in 100 km.

PMID- 24015857
TI  - Assessing posttraumatic stress in military service members: improving efficiency
      and accuracy.
AB  - Posttraumatic stress disorder (PTSD) is assessed across many different
      populations and assessment contexts. However, measures of PTSD symptomatology
      often are not tailored to meet the needs and demands of these different
      populations and settings. In order to develop population- and context-specific
      measures of PTSD it is useful first to examine the item-level functioning of
      existing assessment methods. One such assessment measure is the 17-item PTSD
      Checklist-Military version (PCL-M; Weathers, Litz, Herman, Huska, & Keane, 1993).
      Although the PCL-M is widely used in both military and veteran health-care
      settings, it is limited by interpretations based on aggregate scores that ignore
      variability in item endorsement rates and relatedness to PTSD. Based on item
      response theory, this study conducted 2-parameter logistic analyses of the PCL-M
      in a sample of 196 service members returning from a yearlong, high-risk
      deployment to Iraq. Results confirmed substantial variability across items both
      in terms of their relatedness to PTSD and their likelihood of endorsement at any
      given level of PTSD. The test information curve for the full 17-item PCL-M peaked
      sharply at a value of theta = 0.71, reflecting greatest information at
      approximately the 76th percentile level of underlying PTSD symptom levels in this
      sample. Implications of findings are discussed as they relate to identifying more
      efficient, accurate subsets of items tailored to military service members as well
      as other specific populations and evaluation contexts.

PMID- 24015859
TI  - The internet administration version of the 20-item Toronto alexithymia scale.
AB  - Researchers are increasingly administering tests developed and validated in paper
      format via the Internet. Yet, the equivalence between paper and Internet
      concerning administration of tests is not typically demonstrated. We evaluated
      the reliability, factorial and external validity, and measurement equivalency of
      the Internet version of the 20-item Toronto Alexithymia Scale (TAS-20; Bagby,
      Parker, & Taylor, 1994; Bagby, Taylor, & Parker, 1994; Lumley et al., 2007) vis-a
      vis the paper version. Participants (N = 621) completed the TAS-20 either on the
      Internet or on paper. Reliability and item-to-scale homogeneity were evaluated
      for each format. We used confirmatory factor analyses (CFAs) to evaluate
      factorial validity and used CFA-based factorial invariance procedures to
      determine measurement equivalency. Alpha coefficients and mean interitem
      correlations (MICs) were adequate for the full-scale TAS-20 Internet and paper
      versions and the difficulty identifying feelings (DIF) and difficulty describing
      feelings (DDF) factor scale test scores; in both formats, alpha and MICs were
      poorer for externally oriented thinking (EOT) factor test scores compared to
      scores for the DIF and DDF. The fit of the 3-factor structure of the TAS-20 was
      adequate for both formats. Factorial invariance across formats was also
      demonstrated; mean scores for the total scale and each factor scale were not
      different across formats. Correlations with the domain and facet scales of the
      Revised NEO Personality Inventory (Costa & McCrae, 1992b) were mostly similar
      across formats. The Internet and paper versions of the TAS-20 are comparably
      reliable and valid. An Internet version of the TAS-20 expands opportunities to
      collect data and permits generalizing of results across studies using the
      different modes of administration.

PMID- 24015858
TI  - Personality heterogeneity in PTSD: distinct temperament and interpersonal
      typologies.
AB  - Researchers examining personality typologies of posttraumatic stress disorder
      (PTSD) have consistently identified 3 groups: low pathology, internalizing, and
      externalizing. These groups have been found to predict functional severity and
      psychiatric comorbidity. In this study, we employed Latent Profile Analysis to
      compare this previously established typology, grounded in temperament traits
      (negative emotionality; positive emotionality; constraint), to a novel typology
      rooted in interpersonal traits (dominance; warmth) in a sample of individuals
      with PTSD (n = 155). Using Schedule for Nonadaptive and Adaptive Personality
      (SNAP) traits to create latent profiles, the 3-group temperament model was
      replicated. Using Interpersonal Circumplex (IPC) traits to create latent
      profiles, we identified a 4-group solution with groups varying in interpersonal
      style. These models were nonredundant, indicating that the depiction of
      personality variability in PTSD depends on how personality is assessed. Whereas
      the temperament model was more effective for distinguishing individuals based on
      distress and comorbid disorders, the interpersonal model was more effective for
      predicting the chronicity of PTSD over the 10 year course of the study. We
      discuss the potential for integrating these complementary temperament and
      interpersonal typologies in the clinical assessment of PTSD.

PMID- 24015860
TI  - Operating characteristics of the PTSD checklist in a military primary care
      setting.
AB  - The Department of Defense (DoD) is implementing universal behavioral health
      screening for all DoD health-care beneficiaries presenting to military primary
      care clinics. The PTSD Checklist-Civilian Version (PCL-C; Weathers, Litz, Herman,
      Huska, & Keane, 1993) is used for the identification of posttraumatic stress
      disorder (PTSD); however, the operating characteristics of the PCL-C remain
      unstudied in this population. This study examined the operating characteristics
      of the PCL-C in a sample of 213 patients from 3 Washington, D.C., area military
      primary care clinics. Blinded raters independently assessed PTSD using the PTSD
      Symptom Scale Interview (Foa, Riggs, Dancu, & Rothbaum, 1993) as the diagnostic
      criterion standard. The receiver operating characteristic curve revealed that PCL
      C scores accounted for 92% of the area under the curve. A PCL-C score of 31
      optimized sensitivity (0.93) and specificity (0.90), and the multilevel
      likelihood ratio was 5.50 (95% confidence interval [2.26, 13.37]). Internal
      consistency (0.97) and test-retest reliability (0.87 after a median 13 days) were
      strong. Results suggest that a PCL-C score of 31 is the optimal cutoff score for
      use in a military primary care setting serving active duty service members,
      dependents, and retirees. These findings offer military primary care providers
      preliminary data to interpret PCL-C scores and to inform treatment decisions as
      part of routine clinical practice.

PMID- 24015861
TI  - Characterization of trans-2-[4-[(dimethylamino)styryl]benzothiazole as an
      ultrafast isomerization probe and a modifed Kramers theory analysis.
AB  - The photophysics of trans-2-[4-(dimethylamino)styryl]benzothiazole (DMASBT) was
      investigated by electronic structure calculations and steady-state and time
      resolved emission spectroscopy in a wide range of solvents, including temperature
      and pressure dependence. DMASBT undergoes a facile photoinduced trans-cis
      isomerization similar to the reaction of trans-stilbene. The cis isomer has a
      lifetime of ~1 ps and does not contribute appreciably to the steady-state
      emission spectrum. The absorption spectrum of the cis form overlaps that of the
      trans form such that considerable care is needed in determining correct emission
      quantum yields. The approximate equality of absorption and emission transition
      moments of DMASBT in all solvents indicates that absorption and emission involve
      a single excited state with high radiative rate. The low quantum yields of DMASBT
      in low-viscosity solvents reflect emission lifetimes in the 20-50 ps range. The
      nonradiative rates of DMASBT, which are assumed to measure the rate of
      isomerization in S1, depend upon both solvent viscosity and polarity. A modified
      Kramers analysis, which allows for a polarity-dependent barrier height, provides
      a satisfactory description of these rates but only if it is assumed that friction
      in alcohol solvents is more weakly dependent upon viscosity than in other types
      of solvents. 

PMID- 24015862
TI  - Multifactorial impact of channel beta-subunit gene mutation on automaticity.

PMID- 24015864
TI  - Equine exuberant granulation tissue and human keloids: a comparative
      histopathologic study.
AB  - OBJECTIVE: To compare histopathologic features of a fibroproliferative disorder
      in horses (exuberant granulation tissue-EGT) and people (keloid). SAMPLE
      POPULATION: Archival tissue samples of EGT (n = 8) and keloid (12). METHODS:
      After automated hematoxylin and eosin, histochemical (Gomori trichrome, Verhoeff
      van Gieson elastin) and immunohistochemical (vimentin, alpha-smooth muscle actin,
      CD34, CD68, CD117) stainings, tissue sections were evaluated using a semi
      quantitative grading scale for presence or absence of ulceration, keloidal
      collagen, myofibroblasts, and elastic fibers as well as degree of inflammation,
      fibrosis, vascularity, and orientation of collagen fibers. RESULTS: Superficial
      dermis and deep dermis of both horses and people had increased numbers of
      haphazardly oriented thickened collagen fibers; however, only keloids contained
      "keloidal" collagen. Fibroblast numbers were markedly increased in both groups
      but only EGT had myofibroblasts. Minimal vascularity was observed in the deep
      dermis of both groups. The superficial dermis in EGT was characterized by small
      vessels within immature granulation tissue. Macrophages and mast cells were
      infrequently found in both groups but polymorphonuclear cells were markedly
      increased in EGT. CONCLUSIONS: Humans and horses are the only mammals known to
      naturally develop excessive granulation during wound healing; however,
      similarities and differences between fibroblast populations and associated
      collagen have not been reported. Inflammatory response may contribute to observed
      differences in the cellular populations, with EGT possessing markedly increased
      myofibroblasts, small vessels, and acute inflammatory cells compared with
      keloids. Further work is warranted to develop common treatment strategies for
      these fibroproliferative conditions.

PMID- 24015863
TI  - History of dating violence and the association with late adolescent health.
AB  - BACKGROUND: The present investigation expands upon prior studies by examining the
      relationship between health in late adolescence and the experience of
      physical/sexual and non-physical dating violence victimization, including dating
      violence types that are relevant to today's adolescents (e.g., harassment via
      email and text messaging). We examined the relationship between physical/sexual
      and non-physical dating violence victimization from age 13 to 19 and health in
      late adolescence/early adulthood. METHODS: The sample comprised 585 subjects
      (ages 18 to 21; mean age, 19.8, SD = 1.0) recruited from The Ohio State
      University who completed an online survey to assess: 1) current health
      (depression, disordered eating, binge drinking, smoking, and frequent sexual
      behavior); and 2) dating violence victimization from age 13 to 19
      (retrospectively assessed using eight questions covering physical, sexual, and
      non-physical abuse, including technology-related abuse involving
      stalking/harassment via text messaging and email). Multivariable models compared
      health indicators in never-exposed subjects to those exposed to physical/sexual
      or non-physical dating violence only. The multivariable models were adjusted for
      age and other non-dating abuse victimization (bullying; punched, kicked, choked
      by a parent/guardian; touched in a sexual place, forced to touch someone
      sexually). RESULTS: In adjusted analyses, compared to non-exposed females,
      females with physical/sexual dating violence victimization were at increased risk
      of smoking (prevalence ratio = 3.95); depressive symptoms (down/hopeless, PR =
      2.00; lost interest, PR = 1.79); eating disorders (using diet aids, PR = 1.98;
      fasting, PR = 4.71; vomiting to lose weight, PR = 4.33); and frequent sexual
      behavior (5+ intercourse and oral sex partners, PR = 2.49, PR = 2.02; having anal
      sex, PR = 2.82). Compared to non-exposed females, females with non-physical
      dating violence only were at increased risk of smoking (PR = 3.61), depressive
      symptoms (down/hopeless, PR = 1.41; lost interest, PR = 1.36), eating disorders
      (fasting, PR = 3.37; vomiting, PR = 2.66), having 5+ intercourse partners (PR =
      2.20), and having anal sex (PR = 2.18). For males, no health differences were
      observed for those experiencing physical/sexual dating violence compared to those
      who did not. Compared to non-exposed males, males with non-physical dating
      violence only were at increased risk of smoking (PR = 3.91) and disordered eating
      (fasting, using diet aids, vomiting, PR = 2.93). CONCLUSIONS: For females, more
      pronounced adverse health was observed for those exposed to physical/sexual
      versus non-physical dating violence. For both females and males, non-physical
      dating violence victimization contributed to poor health.

PMID- 24015865
TI  - Barriers to antipsychotic discontinuation in nursing homes: an exploratory study.
AB  - OBJECTIVES: Despite safety warnings on serious adverse effects and guidance
      advising discontinuation, antipsychotic use in nursing homes remains high.
      Studies documenting the barriers experienced to antipsychotic discontinuation are
      rare. This exploratory study investigates the willingness of nurses and general
      practitioners (GPs) as well as the barriers to undertake antipsychotic
      discontinuation. DESIGN AND SETTING: A mixed-method study involving an expert
      meeting, followed by a survey using structured questionnaires distributed to
      responsible nurses (primary caregivers) and treating GPs on selected nursing home
      residents in Belgian nursing homes to generate case-specific information.
      RESULTS: Antipsychotic users (n = 113) had a mean age of 81 years (range 57-97);
      62% were female and 81% had moderate to severe cognitive impairment. Nurses and
      GPs indicated a willingness for antipsychotic discontinuation in a small
      proportion of residents, 13.8% and 12.2%, respectively, with a shared willingness
      in only 4.2%. Residents for whom there was a higher willingness to try
      antipsychotic discontinuation were generally older (mean age 84.6 vs. 80.3, p =
      0.07), had high physical dependency (ADL > 14, 93.3% vs. 60.9%, p = 0.01) and
      resided on a ward with controlled access (80.0% vs. 45.7%, p = 0.02). In
      contrast, residents for whom there was a significant lower willingness for
      discontinuation already had a previously failed discontinuation effort, and may
      present risk of harm to themselves or to others. Nurses working longer on the
      ward, with lower education, presented higher barriers to discontinuation of
      antipsychotics. CONCLUSION: Nurses and GPs share a very low willingness and high
      barriers to antipsychotic discontinuation. To implement discontinuation programs,
      complex multidisciplinary interventions should be offered taking existing
      barriers into account.

PMID- 24015866
TI  - Protein-tyrosine phosphatases: a new frontier in platelet signal transduction.
AB  - Platelet activation must be tightly controlled in order to allow platelets to
      respond rapidly to vascular injury and prevent thrombosis from occurring. Protein
      tyrosine phosphorylation is one of the main ways in which activation signals are
      transmitted in platelets. Although much is known about the protein-tyrosine
      kinases (PTKs) that initiate and propagate activation signals, relatively little
      is known about the protein-tyrosine phosphatases (PTPs) that modulate these
      signals in platelets. PTPs are a family of enzymes that dephosphorylate tyrosine
      residues in proteins and regulate signals transmitted within cells. PTPs have
      been implicated in a variety of pathological conditions, including cancer,
      diabetes and autoimmunity, but their functions in hemostasis and thrombosis
      remain largely undefined. Exciting new findings from a number of groups have
      revealed that PTPs are in fact critical regulators of platelet activation and
      thrombosis. The primary aim of this review is to highlight the unique and
      important functions of PTPs in regulating platelet activity. Establishing the
      functions of PTPs in platelets is essential to better understand the molecular
      basis of thrombosis and may lead to the development of improved antithrombotic
      therapies. 

PMID- 24015867
TI  - High yield growth of patterned vertically aligned carbon nanotubes using inkjet
      printed catalyst.
AB  - This study reports on the fabrication of vertically aligned carbon nanotubes
      localized at specific sites on a growth substrate by deposition of a nanoparticle
      suspension using inkjet printing. Carbon nanotubes were grown with high yield as
      vertically aligned forests to a length of approximately 400 MUm. The use of
      inkjet printing for catalyst fabrication considerably improves the production
      rate of vertically aligned patterned nanotube forests compared with conventional
      patterning techniques, for example, electron beam lithography or
      photolithography. 

PMID- 24015868
TI  - Hydration behavior of poly(ethylene oxide)s in aqueous solution as studied by
      near-infrared spectroscopic techniques.
AB  - Near-infrared (NIR) absorption measurements over a wavenumber range from 4000 to
      12000 cm(-1) were used to investigate hydration behavior of poly(ethylene oxide)s
      bearing molar masses of 3 * 10(3) (PEO3) and 20 * 10(3) (PEO20) in aqueous
      solution at a dilute regime. NIR absorption spectra for solutions were perfectly
      decomposed into three components: bulk water, PEOs, and hydrated water to PEOs.
      While amounts of each component were proportional to the concentrations of PEOs
      (cEO), the wavenumber dependence of each spectrum was independent of cEO and also
      the molar masses of PEOs. A newly determined NIR absorption spectrum of hydrated
      water molecules to PEOs found in a wavenumber range from 5500 to 7500 cm(-1) was
      well described with the summation of two Gaussian-type vibration modes possessing
      the same magnitude, which were observed at different wavenumbers of 6480 and 6910
      cm(-1), respectively. Each mode was assigned to O-H stretching first overtone of
      water molecules hydrated directly to ether oxygen atoms (6480 cm(-1)) and water
      oxygen atoms (6910 cm(-1)) belonging to the secondary hydration layer. 

PMID- 24015869
TI  - MR imaging features of triple-negative breast cancers.
AB  - Triple-negative (TN) breast cancers, which are associated with a more aggressive
      clinical course and poorer prognosis, often present with benign imaging features
      on mammography and ultrasound. The purpose of this study was to compare the
      magnetic resonance imaging features of TN breast cancers with estrogen (ER) and
      progesterone (PR) positive, human epidermal growth factor receptor (HER2)
      negative cancers. Retrospective review identified 140 patients with TN breast
      cancer who underwent a preoperative breast MRI between 2003 and 2008. Comparison
      was made to 181 patients with ER+/PR+/HER2- cancer. Breast MRIs were
      independently reviewed by two radiologists blinded to the pathology.
      Discrepancies were resolved by a third radiologist. TN cancers presented with a
      larger tumor size (p = 0.002), higher histologic grade (<0.001), and were more
      likely to be unifocal (p = 0.018) compared with ER+/PR+/HER2- tumors. MRI
      features associated with TN tumors included mass enhancement (p = 0.026), areas
      of intratumoral high T2 signal intensity (p < 0.001), lobulated shape (p <
      0.001), rim enhancement (p < 0.001), and smooth margins (p = 0.005). Among the TN
      tumors with marked necrosis, 26% showed a large central acellular zone of
      necrosis.

PMID- 24015870
TI  - Laparoscopic transperitoneal heminephrectomy for duplex kidney in infants and
      children: a comparative study.
AB  - BACKGROUND AND OBJECTIVE: Evaluation of the feasibility, safety, and outcome of
      laparoscopic heminephrectomy for duplex kidneys in children above and below the
      age of 12 months. PATIENTS AND METHODS: The transperitoneal surgical technique
      included division of the parenchyma with a sealing device (LigaSureTM; Covidien,
      Mansfield, MA) and amputation of the ureter as low as possible. A follow-up study
      was performed. Patients' records were analyzed retrospectively for operative
      details and postoperative complications. Long-term outcome was assessed during
      follow-up visits and a final telephone interview. Outcome was compared between
      two groups: Group 1 (G1), age at surgery<12 months; Group 2 (G2), age at surgery
      >12 months. RESULTS: Between July 2004 and September 2012, in total, 22
      laparoscopic heminephrectomies (20 upper poles and 2 lower poles) were performed
      in 20 patients (G1, 12 cases; G2, 10 cases). A mean (range) age at surgery was
      7.1 (3-11) months in G1 and 49.4 (15-128) months in G2. Mean (range) operative
      time was 152 (81-220) min in G1 and 197 (90-265) min in G2 (P=.06). All
      procedures were completed laparoscopically. Major postoperative complication was
      one urinoma in G1, which was surgically revised. Mean hospital stay was 3.6 days
      (G1, 4.0 days; G2, 3.1 days). During long-term follow-up (median, 5.2 years)
      febrile urinary tract infections occurred to the same extent in both groups (G1,
      1/12; G2, 2/10; P=.57). CONCLUSIONS: Laparoscopic transperitoneal heminephrectomy
      for duplex kidneys is safe and feasible even in small infants. Long-term results
      are excellent irrespective of the patient's age.

PMID- 24015871
TI  - A novel laparoscopic-assisted approach to the repair of pediatric femoral
      hernias.
AB  - BACKGROUND: Femoral hernias in young children are relatively rare and can be
      difficult to diagnose as they are often mistaken for inguinal hernias. Although a
      few reports have described laparoscopic techniques, most traditional repair
      methods still focus on an open approach using either an inguinal or crural
      incision. Here we describe a laparoscopic-assisted technique that is buttressed
      by a cigarette of mesh for the repair of this uncommon pediatric entity. SUBJECTS
      AND METHODS: We report three consecutive cases of children with femoral hernias
      repaired with only two small incisions: a 5-mm umbilical incision for a 30
      degrees  camera and a 1-cm groin incision for dissection and ligation of the
      hernia sac. After sac ligation, the repair was buttressed with a small mesh
      cigarette. RESULTS: Using this approach, right femoral hernias were repaired
      without complication in three children, between 8 and 9 years of age. Two
      patients had ipsilateral indirect inguinal hernias. No contralateral groin
      hernias were identified in any of the patients. Operative time averaged 40
      minutes, recovery time was quick, and follow-up at 6 months revealed good
      cosmesis. CONCLUSIONS: This laparoscopic-assisted approach to pediatric femoral
      hernia repair with a small mesh plug is a safe, effective, and efficient
      technique. Because only two incisions are required, postoperative pain is
      minimal, and cosmesis is excellent. Nonetheless, more patients and longer follow
      up will be required to accurately judge the long-term implications of this novel
      technique.

PMID- 24015872
TI  - Factors predicting mood changes in oral contraceptive pill users.
AB  - BACKGROUND: Over 100 million women worldwide are using oral contraceptives pills
      (OCP) and mood changes were being as the primary reason for OCP discontinuation.
      The purpose of this study was to determine the prevalence and predicting factors
      of mood changes in oral contraceptive pills users. METHODS: This was a cross
      sectional study of 500 women aged 15-49 years old using low dose (LD) pills
      attending family planning centers in Ahwaz, Iran. Data were collected via face-to
      face interviews using a structured questionnaire including items on demographic,
      self-efficacy and mood change. Both univarate and multiple logistic regression
      analyses were performed to assess the relationship between reported mood change
      and the independent variables. RESULTS: In all 406 women reported that they did
      experience OCP side effects. Of these, 37.7% of women (n =153) reported mood
      changes due to OCP use. The results of multiple logistic regression revealed that
      place of living (OR =2.57, 95% CI = 1.06-6.20, p =0.03), not receiving
      information on OCP side effects (OR =1.80, 95% CI = 1.15-2.80, p =0.009), and
      lower self-efficacy (OR = 0.87, 95% CI = 0.80-0.94, p =0.001) were significant
      predictors of mood changes. CONCLUSION: The findings from this study indicated
      that the prevalence of reported mood changes due to OCP use among Iranian women
      appeared to be consistent with other studies. In addition the findings showed
      that receiving information on OCP side effects from health care workers and self
      efficacy were important predicting factors for mood changes. Indeed implementing
      educational programs and improving self-efficacy among women are recommended.

PMID- 24015873
TI  - Predicting whole genome protein interaction networks from primary sequence data
      in model and non-model organisms using ENTS.
AB  - BACKGROUND: The large-scale identification of physical protein-protein
      interactions (PPIs) is an important step toward understanding how biological
      networks evolve and generate emergent phenotypes. However, experimental
      identification of PPIs is a laborious and error-prone process, and current
      methods of PPI prediction tend to be highly conservative or require large amounts
      of functional data that may not be available for newly-sequenced organisms.
      RESULTS: In this study we demonstrate a random-forest based technique, ENTS, for
      the computational prediction of protein-protein interactions based only on
      primary sequence data. Our approach is able to efficiently predict interactions
      on a whole-genome scale for any eukaryotic organism, using pairwise combinations
      of conserved domains and predicted subcellular localization of proteins as input
      features. We present the first predicted interactome for the forest tree Populus
      trichocarpa in addition to the predicted interactomes for Saccharomyces
      cerevisiae, Homo sapiens, Mus musculus, and Arabidopsis thaliana. Comparing our
      approach to other PPI predictors, we find that ENTS performs comparably to or
      better than a number of existing approaches, including several that utilize a
      variety of functional information for their predictions. We also find that the
      predicted interactions are biologically meaningful, as indicated by similarity in
      functional annotations and enrichment of co-expressed genes in public microarray
      datasets. Furthermore, we demonstrate some of the biological insights that can be
      gained from these predicted interaction networks. We show that the predicted
      interactions yield informative groupings of P. trichocarpa metabolic pathways,
      literature-supported associations among human disease states, and theory
      supported insight into the evolutionary dynamics of duplicated genes in
      paleopolyploid plants. CONCLUSION: We conclude that the ENTS classifier will be a
      valuable tool for the de novo annotation of genome sequences, providing initial
      clues about regulatory and metabolic network topology, and revealing
      relationships that are not immediately obvious from traditional homology-based
      annotations.

PMID- 24015874
TI  - Morphological and health-related changes associated with a 12-week self-guided
      exercise programme in overweight adults: a pilot study.
AB  - Over 12 weeks, supervised physical activity (PA) interventions have demonstrated
      improvements in morphological and health parameters, whereas community walking
      programmes have not. The present study piloted a self-guided programme for
      promoting PA and reducing sedentary behaviour in overweight individuals and
      measured its effect on a range of health outcomes. Six male and 16 female
      sedentary adults aged 48.5 +/- 5.5 years with body mass index (BMI) 33.4 +/- 6.3
      kg m(-2) were assessed for anthropometric variables, blood pressure, functional
      capacity, well-being and fatigue. After an exercise consultation, participants
      pursued their own activity and monitored PA points weekly. At baseline, mid-point
      and 12 weeks, eight participants wore activity monitors, and all participants
      undertook a 5-day food diary to monitor dietary intake. In 17 completers, mass,
      BMI, sit-to-stand, physical and general fatigue had improved by 6 weeks. By 12
      weeks, waist, sagittal abdominal diameter (SAD), diastolic blood pressure, well
      being and most fatigue dimensions had also improved. Throughout the intervention,
      PA was stable, energy intake and lying time decreased and standing time
      increased; thus, changes in both energy intake and expenditure explain the health
      related outcomes. Observed changes in function, fatigue and quality of life are
      consistent with visceral fat loss and can occur at levels of weight loss which
      may not be considered clinically significant.

PMID- 24015875
TI  - High-content screening assay for identification of chemicals impacting
      cardiovascular function in zebrafish embryos.
AB  - Targeted assays are needed to better evaluate effects of chemicals on
      organogenesis and begin classification of chemicals by toxicologically relevant
      modes-of-action. Using transgenic zebrafish (fli1:egfp) that stably express eGFP
      within vascular endothelial cells, we have developed and optimized a 384-well
      based high-content screening (HCS) assay that enables us to screen and identify
      chemicals affecting cardiovascular function at sublethal, nonteratogenic
      concentrations. Following static exposure of one embryo per well from 5 to 72 h
      postfertilization (hpf), automated image acquisition procedures and custom image
      analysis protocols are used to quantify body length, circulation, heart rate,
      pericardial area (a biomarker for cardiac looping defects), and intersegmental
      vessel area within freshly hatched live embryos. After optimizing 72 hpf
      anesthetization procedures, we evaluated each end point across four independent
      control plates containing 384 initial embryos per plate. Survival and imaging
      success rates across these plates ranged from 93 to 99% and 42 to 74%,
      respectively. Criteria were then defined for assay success and analysis of
      treatments, and 10 chemicals were screened for targeted effects on cardiovascular
      function. Compared to existing zebrafish-based assays, this method provides a
      comprehensive discovery platform with (1) increased sample sizes; (2) broad
      concentration-response format; and (3) the ability to identify chemicals that
      target cardiovascular function at nonteratogenic concentrations. 

PMID- 24015876
TI  - Elastometry of deflated capsules: elastic moduli from shape and wrinkle analysis.
AB  - Elastic capsules, prepared from droplets or bubbles attached to a capillary (as
      in a pendant drop tensiometer), can be deflated by suction through the capillary.
      We study this deflation and show that a combined analysis of the shape and
      wrinkling characteristics enables us to determine the elastic properties in situ.
      Shape contours are analyzed and fitted using shape equations derived from
      nonlinear membrane-shell theory to give the elastic modulus, Poisson ratio and
      stress distribution of the membrane. We include wrinkles, which generically form
      upon deflation, within the shape analysis. Measuring the wavelength of wrinkles
      and using the calculated stress distribution gives the bending stiffness of the
      membrane. We compare this method with previous approaches using the Laplace-Young
      equation and illustrate the method on two very different capsule materials:
      polymerized octadecyltrichlorosilane (OTS) capsules and hydrophobin (HFBII)
      coated bubbles. Our results are in agreement with the available rheological data.
      For hydrophobin coated bubbles, the method reveals an interesting nonlinear
      behavior consistent with the hydrophobin molecules having a rigid core surrounded
      by a softer shell. 

PMID- 24015877
TI  - Multiple unfolding pathways of leucine binding protein (LBP) probed by single
      molecule force spectroscopy (SMFS).
AB  - Experimental studies on the folding and unfolding of large multi-domain proteins
      are challenging, given the proteins' complex energy landscapes with multiple
      intermediates. Here, we report a mechanical unfolding study of a 346-residue, two
      domain leucine binding protein (LBP) from the bacterial periplasm. Forced
      unfolding of LBP is a prerequisite for its translocation across the cytoplasmic
      membrane into the bacterial periplasm. During the mechanical stretching of LBP,
      we observe that 38% of the unfolding flux followed a two-state pathway, giving
      rise to a single unfolding force peak at ~70 pN with an unfolding contour length
      of 120 nm in constant-velocity single-molecule pulling experiments. The remaining
      62% of the unfolding flux followed multiple three-state pathways, with
      intermediates having unfolding contour lengths in the range ~20-85 nm. These
      results suggest that the energy landscape of LBP is complex, with multiple
      intermediate states, and a large fraction of molecules go through intermediate
      states during the unfolding process. Furthermore, the presence of the ligand
      leucine increased the unfolding flux through the two-state pathway from 38% to
      65%, indicating the influence of ligand binding on the energy landscape. This
      study suggests that unfolding through parallel pathways might be a general
      mechanism for the large two-domain proteins that are translocated to the
      bacterial periplasmic space.

PMID- 24015878
TI  - Conflicting medication information: prevalence, sources, and relationship to
      medication adherence.
AB  - Conflicting medication information has been defined as contradictory information
      about a medication topic from two or more sources. The objective of this study
      was to determine whether arthritis patients are exposed to conflicting medication
      information, to document sources of conflicting information, and to explore
      whether conflicting information is associated with sociodemographic factors,
      clinical characteristics, and medication adherence. Using an online survey,
      arthritis patients (N = 328) reported how often they received conflicting
      information about 12 medication topics as well as sources of conflicting
      information, demographic/clinical characteristics, and medication adherence. A
      linear regression model, which controlled for various demographic/clinical
      factors, determined whether conflicting information was associated with
      medication adherence. The majority of patients (80.1%) received conflicting
      information and were most likely to receive conflicting information about
      medication risks. Physicians, media sources, and the Internet were the most
      common sources of conflicting information. Less conflicting information (B =
      0.13, p < .05), more information source use (B = 0.22, p < .01), and lower
      perceived regimen complexity (B =-0.17, p < .05) were associated with better
      medication adherence. In conclusion, conflicting medication information is
      pervasive, comes from a variety of sources, and may negatively affect patient
      health outcomes. To potentially decrease exposure to conflicting information,
      providers should direct patients to high-quality medication information sources. 

PMID- 24015879
TI  - Synthesis of a non-aggregating bay-unsubstituted perylene bisimide dye with
      latent bromo groups for C-C cross coupling.
AB  - To address the absence of synthetic routes to access easily functionalizable, non
      aggregating, and soluble bay-unsubstituted perylene bisimide dyes, an efficient,
      three-step, multigram-scale synthesis of the divergent building block N,N'-bis(4
      bromo-2,6-diisopropylphenyl)perylene-3,4:9,10-tetracarboxylic bisimide is
      reported. Suzuki coupling yields new dyes that maintain excellent solubility and
      exhibit unity quantum yields in CHCl3, THF, toluene, and CH3CN. The methodology
      reported here enables access to dyes with sensitive functional groups such as
      aldehydes that are not accessible by traditional imidization routes. 

PMID- 24015880
TI  - The Toxoplasma gondii kinetochore is required for centrosome association with the
      centrocone (spindle pole).
AB  - The kinetochore is a multi-protein structure assembled on eukaryotic centromeres
      mediating chromosome attachment to spindle microtubules. Here we identified the
      kinetochore proteins Nuf2 and Ndc80 in the apicomplexan parasite Toxoplasma
      gondii. Localization revealed that kinetochores remain clustered throughout the
      cell cycle and colocalize with clustered centromeres at the centrocone, a
      structure containing the spindle pole embedded in the nuclear envelope.
      Pharmacological disruption of microtubules resulted in partial loss of some
      kinetochore and centromere clustering, indicating microtubules are necessary but
      not strictly required for kinetochore clustering. Generation of a TgNuf2
      conditional knock-down strain revealed it is essential for chromosome
      segregation, but dispensable for centromere clustering. The centromeres actually
      remained associated with the centrocone suggesting microtubule binding is not
      required for their interaction with the spindle pole. The most striking
      observation upon TgNuf2 depletion was that the centrosome behaved normally, but
      that it lost its association with the centrocone. This suggests that microtubules
      are essential to maintain contact between the centrosome and chromosomes, and
      this interaction is critical for the partitioning of the nuclei into the two
      daughter parasites. Finally, genetic complementation experiments with mutated
      TgNuf2 constructs highlighted an apicomplexan-specific motif with a putative role
      in nuclear localization. 

PMID- 24015882
TI  - Evolution of anaesthesia care and related events between 1996 and 2010 in
      Switzerland.
AB  - BACKGROUND: Anaesthesia Databank Switzerland (ADS) is a voluntary data registry
      introduced in 1996. Its ultimate goal is to promote quality in anaesthesiology.
      METHODS: The ADS registry analyses routinely recorded adverse events and provides
      benchmark comparisons between anaesthesia departments. Data collection comprises
      a set of 31 variables organised into three modules, one mandatory and two
      optional. RESULTS: In 2010, the database included 2,158,735 anaesthetic
      procedures. Over time, the proportions of older patients have increased, the
      largest group being aged 50-64 years. The percentage of patients with American
      Society of Anesthesiologists (ASA) status 1 has decreased while the percentage of
      ASA status 2 or 3 patients has increased. The most frequent comorbidities
      recorded were hypertension (21%), smoking (16%), allergy (15%) and obesity (12%).
      Between 1996 and 2010, 125,579 adverse events were recorded, of which 34% were
      cardiovascular, 7% respiratory, 39% technical and 20% non-specific. The most
      severe events were resuscitation (50%), oliguria (22%), myocardial ischaemia
      (17%) and haemorrhage (10%). CONCLUSION: Routine ADS data collection contributes
      to the monitoring of trends in anaesthesia care in Switzerland. The ADS system
      has proved to be usable in daily practice, although this remains a constant
      challenge that is highly dependent on local quality management and quality
      culture. Nevertheless, success in developing routine regular feedback to users to
      initiate discussions about anaesthetic events would most likely help strengthen
      departmental culture regarding safety and quality of care.

PMID- 24015881
TI  - Animal toxicity of hairpin pyrrole-imidazole polyamides varies with the turn
      unit.
AB  - A hairpin pyrrole-imidazole polyamide (1) targeted to the androgen receptor
      consensus half-site was found to exert antitumor effects against prostate cancer
      xenografts. A previous animal study showed that 1, which has a chiral amine at
      the alpha-position of the gamma-aminobutyric acid turn (gamma-turn), did not
      exhibit toxicity at doses less than 10 mg/kg. In the same study, a polyamide with
      an acetamide at the beta-position of the gamma-turn resulted in animal morbidity
      at 2.3 mg/kg. To identify structural motifs that cause animal toxicity, we
      synthesized polyamides 1-4 with variations at the alpha- and beta-positions in
      the gamma-turn. Weight loss, histopathology, and serum chemistry were analyzed in
      mice post-treatment. While serum concentration was similar for all four
      polyamides after injection, dose-limiting liver toxicity was only observed for
      three polyamides. Polyamide 3, with an alpha-acetamide, caused no significant
      evidence of rodent toxicity and retains activity against LNCaP xenografts. 

PMID- 24015883
TI  - The effect of insomnia on functional status of community-dwelling older adults.
AB  - This secondary data analysis examined the extent to which fatigue mediates the
      relationship between insomnia and the physical, social, and psychological domains
      of functional status in community-dwelling older adults. Data were obtained from
      209 older adults with insomnia. Regression analysis was used to test the proposed
      mediating role of fatigue. Findings identified insomnia of moderate severity in
      community-dwelling older adults. Insomnia was directly associated with social
      function and indirectly associated with physical and psychological function.
      Fatigue mediated the relationship between insomnia and all three domains of
      functional status. The findings have implications for nursing practice and
      research and highlight the importance of successfully managing insomnia and
      fatigue to promote functioning in older adults.

PMID- 24015884
TI  - The adverse reactions to care scale: identifying and measuring triggers during
      transitions in care.
AB  - Transitions in care tend to be difficult and complicated periods for older
      adults, families, and staff in long-term care facilities. For some older adults,
      care activities and care environments in facilities can lead to adverse
      reactions, such as resisting assistance with care or agitation and anxiety.
      Unfortunately, current tools do not adequately assess for triggers to such
      behaviors. In the current study, the 8-item Adverse Reactions to Care (ARC) scale
      was developed and tested with 89 older adults and their caregivers (N = 89).
      Exploratory factor analysis revealed the ARC scale loaded onto two distinct
      factors: (a) reactions to care activities and (b) reactions to care environments,
      with high overall reliability (alpha = 0.84). With additional testing, the ARC
      scale may be useful for clinicians in long-term care settings and for researchers
      focused on understanding care transitions for older adults.

PMID- 24015885
TI  - Transitional care management services: optimizing medication reconciliation to
      improve the care of older adults.
AB  - Recent establishment of Transitional Care Management (TCM) services by the
      Centers for Medicare & Medicaid Services demonstrates the shift in emphasis
      toward interventions that reduce hospital and emergency department utilization.
      Older adults are especially vulnerable during these transitions in care due to
      the increased risk of medication-related problems. Thorough medication
      reconciliation can preemptively identify potential medication-related problems
      such as medication errors, high-risk medications, and adverse effects.

PMID- 24015886
TI  - Nurse entrepreneurs, arise!: improving lives of older adults by bringing your
      ideas to market.
AB  - Many functions that nurses carry out require the use of various technologies, yet
      nurses are rarely involved in the development and/or testing of technology. The
      purpose of this article is to provide an introduction to the world of technology
      development to help nurses understand how to become involved in this endeavor. An
      illustration of a newly developed technology will be used to further clarify the
      steps.

PMID- 24015887
TI  - Family caregivers of individuals with frontotemporal dementia: examining the
      relationship between coping and caregiver physical and mental health.
AB  - To identify strategies to assist family caregivers of individuals with
      frontotemporal dementia (FTD) in dealing with their caregiving demands, nurses
      must understand these family members' unique needs and how they currently deal
      with their demands. The purpose of this study was to examine the relationship
      between coping and caregiver physical and mental health among FTD family
      caregivers. Participants were primary caregivers of individuals with FTD (with
      behavioral symptoms) living at home (N = 61). A small positive association was
      noted between problem-focused coping and caregiver physical health (r = 0.29, p <
      0.05), and a small but nonsignificant positive correlation was noted between
      emotion-focused coping and caregiver mental health (r = 0.21, p = 0.10). However,
      multiple regression analysis showed that emotion-focused coping (beta = 0.46, p <
      0.05) made a statistically significant, unique contribution to caregiver mental
      health and explained approximately 14% of its variance. These findings support
      the potential value of emotion-focused coping strategies when dealing with
      behavioral symptoms manifested by individuals with FTD.

PMID- 24015888
TI  - Lives to cherish: moments to live for.

PMID- 24015889
TI  - The CLOQS trial protocol: a cluster-randomized trial evaluating a simple, low
      cost intervention to reduce treatment times in acute stroke.
AB  - RATIONALE: In acute stroke, time is brain: faster tissue plasminogen activator
      treatment improves patient outcomes. Published guidelines for door-to-scanner
      time are <25 minutes, and for door-to-needle time <60 minutes. These benchmarks
      are rarely met. Paradoxically, the earlier a stroke patient arrives to hospital,
      the longer treatment takes. There is an urgent need to shift focus away from the
      4.5 hour time window, towards treatment times <60 minutes. AIMS: The objective of
      the Countdown Lights to Optimize Quality in acute Stroke (CLOQS) trial is to
      determine whether a simple, low-cost organizational behavior intervention, a
      large, red stopwatch timer attached to the stretcher upon arrival, will decrease
      door-to-scanner and door-to-needle treatment times for tissue plasminogen
      activator-treated patients. DESIGN: A multicenter, time-clustered randomized
      control trial. The stopwatch timers will be used in Emergency Departments for all
      acute stroke patients across the University of Toronto Stroke Program. The order
      of intervention (ON) and control (OFF) blocks will be randomly assigned in a 1:1
      ratio over an 18 month period. Blocks will be weighted in a 2:1 ratio of ON/OFF
      using a permuted block design (ON blocks last two weeks; OFF blocks last one
      week). STUDY OUTCOMES: The primary end-point is percentage of patients achieving
      best-practice guidelines (door-to-needle treatment time <60 minutes). Secondary
      end-points are median time intervals for 1) door-to-scanner and 2) door-to-needle
      times during ON versus OFF blocks. Tertiary end-points are in-hospital mortality
      and time series analysis to determine change in treatment times from prior to
      study onset through study completion.

PMID- 24015890
TI  - Equine ulnar fracture repair with locking compression plates can be associated
      with inadvertent penetration of the lateral cortex of the radius.
AB  - OBJECTIVE: To evaluate if the use of locking head screws (LHS) in the distal
      holes of a locking compression plate (LCP) applied to the caudal aspect of the
      ulna to treat equine ulnar fractures is associated with a risk of injury to the
      lateral cortex of the radius. STUDY DESIGN: Controlled laboratory study. SAMPLE
      POPULATION: Cadaveric equine forelimbs (n = 8 pair). METHODS: After transverse
      ulnar osteotomy, osteosynthesis was performed with a narrow 10-13 hole 4.5/5.0
      LCP applied to the caudal aspect of each ulna. The distal 3 holes were filled
      with 4.5 mm cortex screws (CS) in 1 limb (group 1) and with 5.0 mm LHS
      contralaterally (group 2). CS were inserted in an angle deemed appropriate by the
      surgeon and LHS were inserted perpendicular to the plate. Implant position and
      injury to the lateral cortex of the radius were assessed by radiography, CT, and
      limb dissection. RESULTS: In group 1, injury of the lateral radius cortex did not
      occur. In group 2, 4 limbs and 6/24 LHS were associated with injury of the
      lateral radius cortex by penetration of a LHS. This difference was statistically
      significant. CS were inserted with a mean angle of 17.6 degrees  from the
      sagittal plane in a caudolateral-craniomedial direction. CONCLUSIONS: Use of LHS
      in the distal part of a LCP applied to the caudal aspect of the ulna is
      associated with a risk of inadvertent injury to the lateral cortex of the radius.

PMID- 24015891
TI  - Pacemaker gene mutations, bradycardia, arrhythmias and the coupled clock theory.

PMID- 24015892
TI  - Elevated CO2 decreases the response of the ethylene signaling pathway in Medicago
      truncatula and increases the abundance of the pea aphid.
AB  - The performance of herbivorous insects is greatly affected by plant nutritional
      quality and resistance, which are likely to be altered by rising concentrations
      of atmospheric CO2 . We previously reported that elevated CO2 enhanced biological
      nitrogen (N) fixation of Medicago truncatula, which could result in an increased
      supply of amino acids to the pea aphid (Acyrthosiphon pisum). The current study
      examined the N nutritional quality and aphid resistance of sickle, an ethylene
      insensitive mutant of M. truncatula with supernodulation, and its wild-type
      control A17 under elevated CO2 in open-top field chambers. Regardless of CO2
      concentration, growth and amino acid content were greater and aphid resistance
      was lower in sickle than in A17. Elevated CO2 up-regulated N assimilation and
      transamination-related enzymes activities and increased phloem amino acids in
      both genotypes. Furthermore, elevated CO2 down-regulated expression of 1-amino
      cyclopropane-carboxylic acid (ACC), sickle gene (SKL) and ethylene response
      transcription factors (ERF) genes in the ethylene signaling pathway of A17 when
      infested by aphids and decreased resistance against aphids in terms of lower
      activities of superoxide dismutase (SOD), peroxidase (POD), and polyphenol
      oxidase (PPO). Our results suggest that elevated CO2 suppresses the ethylene
      signaling pathway in M. truncatula, which results in an increase in plant
      nutritional quality for aphids and a decrease in plant resistance against aphids.

PMID- 24015893
TI  - Roughening in electronic growth of Ag on Si(111)-(7*7) surfaces.
AB  - Roughening in the electronic growth of Ag films on Si(111)-(7*7) surfaces for a
      film thickness ranging from 1 to 30 monolayers is reported. Ag films exhibit the
      growth of flat-top plateaus of preferential heights due quantum electronic
      effect. We have observed roughening of the film growth due to instability with
      linear diffusion characterized by the ln(theta)(1/2) dependence of the local
      surface slope, where theta is the Ag coverage. The roughening of the surface
      morphology has been characterized by scaling exponents alpha, beta and 1/z, which
      are determined using scanning tunneling microscopy. Increased value of alpha =
      0.67 +/- 0.04 at the early stage of the electronic growth with two atomic layer
      height flat-top isolated Ag mounds to 0.77 +/- 0.06 at the later stage of the
      growth when isolated mounds coalesce and form percolated structures maintaining
      preferential heights of an even number of atomic layers in the Ag mounds
      indicates the instability in the electronic growth. As a result, interface width
      W increases as a power law of coverage (theta), W ~ theta(beta), with growth
      exponent beta = 0.33 +/- 0.03, and lateral correlation length xi grows as xi ~
      theta(1/z) with 1/z = 0.27 +/- 0.05. 

PMID- 24015894
TI  - The influence of maturation, body size and physical self-perceptions on
      longitudinal changes in physical activity in adolescent girls.
AB  - The aim of this study was to adopt a longitudinal design to explore the direct
      effects of both absolute and relative maturation and changes in body size on
      physical activity, and explore if, and how, physical self-perceptions might
      mediate this effect. We recruited 208 girls (11.8 +/- 0.4 years) at baseline.
      Data were collected at three subsequent time points, each 6 months apart. At 18
      months, 119 girls remained in the study. At each time point, girls completed the
      Physical Activity Questionnaire for Children, the Pubertal Development Scale
      (from which, both a measure of relative and absolute maturation were defined) and
      the Physical Self-Perception Profile, and had physical size characteristics
      assessed. Multilevel modelling for physical activity indicated a significant
      negative effect of age, positive effect for physical condition and sport
      competence and positive association for relatively early maturers. Absolute
      maturation, body mass, waist circumference and sum of skinfolds did not
      significantly contribute to the model. Contrary to common hypotheses, relatively
      more mature girls may, in fact, be more active than their less mature peers.
      However, neither changes in absolute maturation nor physical size appear to
      directly influence changes in physical activity in adolescent girls.

PMID- 24015897
TI  - Predicting aggregation rates of colloidal particles from direct force
      measurements.
AB  - Direct force measurements between negatively charged colloidal latex particles of
      a diameter of 1 MUm were carried out in aqueous solutions of various inorganic
      monovalent and multivalent cations with the multiparticle colloidal probe
      technique based on the atomic force microscope (AFM). The observed force profiles
      were rationalized within the theory of Derjaguin, Landau, Verwey, and Overbeek
      (DLVO). In the presence of monovalent and divalent cations, this theory was
      capable to describe the force profiles correctly down to distances of a few nm.
      At shorter distances, however, a strong non-DLVO attraction was identified. For
      more highly charged cations, an additional and more long-ranged non-DLVO
      attractive force is observed, and it was interpreted by surface charge
      heterogeneities. On the basis of these force profiles, the aggregation rates,
      which were independently measured by light scattering, can be predicted
      relatively well. The main conclusion of this study is that, in the present
      system, direct force measurements do capture the principal interactions driving
      aggregation in colloidal suspensions. 

PMID- 24015895
TI  - A cross-sectional study of frequency and factors associated with dog walking in 9
      10 year old children in Liverpool, UK.
AB  - BACKGROUND: Owning a pet dog could potentially improve child health through
      encouraging participation in physical activity, through dog walking. However,
      evidence to support this is limited and conflicting. In particular, little is
      known about children's participation in dog walking and factors that may be
      associated with this. The objective of this study was to describe the
      participation of children in dog walking, including their own and those belonging
      to somebody else, and investigate factors associated with regular walking with
      their own pet dog. METHODS: Primary school children (n=1021, 9-10 years) from a
      deprived area of Liverpool were surveyed during a 'fitness fun day' as part of
      the SportsLinx project. The 'Child Lifestyle and Pets' survey included questions
      about pet ownership, pet attachment, and dog walking. Multivariable logistic
      regression models were used to investigate factors associated with walking any
      dog, or their own dog, several times a day or more, including level of attachment
      to the dog, dog type, and sociodemographic factors. RESULTS: Overall, 15.4% of
      children reported walking with any dog (their own or belonging to a friend or
      family member) >= once daily, 14.1% several times a week, 27.6% <= once a week,
      and 42.8% never. Dog owning children (37.1% of the population) more often
      reported dog walking 'several times a week or more' (OR=12.30, 95% CI=8.10-18.69,
      P<0.001) compared to those without a dog, but were less likely to report other
      walking without a dog. The majority (59.3%) of dog owning children indicated that
      they usually walked their dog, with 34.6% reporting that they walked their dog >=
      once daily. Attachment score was highly associated with the child reporting
      walking their dog (lower score=higher attachment; OR=0.93, 95% CI=0.89-0.96,
      P<0.001). There was no evidence that gender, ethnicity, sibling status or
      deprivation score was associated with dog walking. Children that reported owning
      Pit Bulls were more likely to report friends walking with their dog than those
      owning non-Pit bull types (OR=10.01, 95% CI=1.52-65.76, P=0.02, respectively).
      CONCLUSIONS: Promotion of supervised walking of suitable pet dogs may be an
      opportunity for increasing physical activity in 9-10 year old children. The
      identification of stronger attachment to dogs regularly walked is similar to
      findings in adult studies.

PMID- 24015896
TI  - Five-fold increase in national prevalence rates of attention
      deficit/hyperactivity disorder medications for children and adolescents with
      autism spectrum disorder, attention-deficit/hyperactivity disorder, and other
      psychiatric disorders: a Danish register-based study.
AB  - OBJECTIVE: The purpose of this study was to estimate the prevalence and time
      trends in prescriptions of methylphenidate, dexamphetamine, and atomoxetine in
      children and adolescents, within three diagnostic groups: 1) autism spectrum
      disorder (ASD), 2) attention-deficit/hyperactivity disorder (ADHD), and 3) other
      psychiatric disorders. METHODS: Data from six different national registers were
      used and merged to identify a cohort of all children and adolescents born in
      Denmark between 1990 and 2001 (n=852,711). Sociodemographic covariates on cohort
      members and their parents and lifetime prescriptions of methylphenidate,
      dexamphetamine, and atomoxetine were extracted from the registers. Prescriptions
      were also stratified by duration (<6 months. vs.>= 6 months). RESULTS: Sixteen
      percent of 9698 children and adolescents with ASD (n=1577), 61% of 11,553
      children and adolescents with ADHD (n=7021) and 3% of 48,468 children and
      adolescents with other psychiatric disorders (n=1537) were treated with one or
      more ADHD medications. There was a significant increase in prescription rates of
      these medications for all three groups. From 2003 to 2010, youth 6-13 years of
      age with ASD, ADHD, and other psychiatric disorders had 4.7-fold (4.4-4.9), 6.3
      fold (6.0-6.4), and 5.5-fold (5.0-5.9) increases, respectively, in prescription
      rates of ADHD medications. CONCLUSION: This is the largest study to date
      assessing stimulant treatment in children and adolescents with ASD, and is the
      first prospective study quantifying the change over time in the prevalence of
      treatment with ADHD medications in a population-based national cohort of children
      and adolescents with ASD. The prevalence of stimulant treatment in youth with ASD
      of 16% is consistent with earlier studies. The past decade has witnessed a clear
      and progressive increase in the prescription rates of medications typically used
      to treat ADHD in children and adolescents in Denmark. This increase is not
      limited to only those with ADHD, but includes others with neuropsychiatric
      disorders, including ASD. The risks and benefits of this practice await further
      study.

PMID- 24015898
TI  - Commercial insurance triples chances of breast cancer survival in a public
      hospital.
AB  - Breast cancer survival is affected both by endogenous factors and exogenous
      factors such as socioeconomic status. This study explored the relationship
      between insurance status and overall survival of 987 female breast cancer
      patients in a population served by a public hospital. All patients were offered
      the same level of care regardless of ability to pay. Of the 987 breast cancer
      patients investigated, 54.6% were African-American. 54.1% of patients were
      insured (commercial insurance or Medicare), 27.1% with Medicaid, and 18.8% who
      were uninsured. Overall median survival was 15.5 years and was not statistically
      significant between Caucasian and African-American women. Median survival times
      were 15.8, 11.3, and 8.2 years for insured, Medicaid, and uninsured groups,
      respectively. Uninsured patients had worse overall survival rates compared with
      insured patients (p < 0.05). Adjusting for other factors (e.g., stage, age, race,
      body mass index, and income), insurance was a significant factor affecting
      survival with hazard ratios of 2.24 and 3.22 for Medicaid and uninsured patients,
      respectively, compared with insured patients. Even in a public hospital, after
      adjusting for potential risk factors, insurance status still proved to be an
      important factor in the survival of breast cancer patients. Further research is
      necessary to identify causal factors related to the survival disparities
      associated with insurance status.

PMID- 24015899
TI  - Shedding light on the sea: Andre Morel's legacy to optical oceanography.
AB  - Andre Morel (1933-2012) was a prominent pioneer of modern optical oceanography,
      enabling significant advances in this field. Through his forward thinking and
      research over more than 40 years, he made key contributions that this field
      needed to grow and to reach its current status. This article first summarizes his
      career and then successively covers different aspects of optical oceanography
      where he made significant contributions, from fundamental work on optical
      properties of water and particles to global oceanographic applications using
      satellite ocean color observations. At the end, we share our views on Andre's
      legacy to our research field and scientific community. 

PMID- 24015900
TI  - Sea ice ecosystems.
AB  - Polar sea ice is one of the largest ecosystems on Earth. The liquid brine
      fraction of the ice matrix is home to a diverse array of organisms, ranging from
      tiny archaea to larger fish and invertebrates. These organisms can tolerate high
      brine salinity and low temperature but do best when conditions are milder.
      Thriving ice algal communities, generally dominated by diatoms, live at the
      ice/water interface and in recently flooded surface and interior layers,
      especially during spring, when temperatures begin to rise. Although protists
      dominate the sea ice biomass, heterotrophic bacteria are also abundant. The sea
      ice ecosystem provides food for a host of animals, with crustaceans being the
      most conspicuous. Uneaten organic matter from the ice sinks through the water
      column and feeds benthic ecosystems. As sea ice extent declines, ice algae likely
      contribute a shrinking fraction of the total amount of organic matter produced in
      polar waters. 

PMID- 24015902
TI  - Internal receptors in insect appendages project directly into a special brain
      neuropile.
AB  - BACKGROUND: The great majority of afferent neurons of insect legs project into
      their segmental ganglion. Intersegmental projections are rare and are only formed
      by sense organs associated with the basal joints of the legs. Such intersegmental
      projections never ascend as far as the brain and they form extensive
      ramifications within thoracic ganglia. A few afferents of chordotonal organs of
      the subcoxal joints ascend as far as the suboesophageal ganglion. RESULTS: We
      describe novel afferent neurons in distal segments of locust legs that project
      directly into the brain without forming ramifications in other ganglia. In the
      brain, the fibres terminate with characteristic terminals in a small neuropile
      previously named the superficial ventral inferior protocerebrum. The somata of
      these neurons are located in the tibiae and tarsi of all legs and they are
      located within branches of peripheral nerves, or closely associated with such
      branches. They are not associated with any accessory structures such as tendons
      or connective tissue strands as typical for insect internal mechanoreceptors such
      as chordotonal organs or stretch receptors. Morphologically they show great
      similarity to certain insect infrared receptors.We could not observe projections
      into the superficial ventral inferior protocerebrum after staining mandibular or
      labial nerves, but we confirm previous studies that showed projections into the
      same brain neuropile after staining maxillary and antennal nerves, indicating
      that most likely similar neurons are present in these appendages also.
      CONCLUSION: Because of their location deep within the lumen of appendages the
      function of these neurons as infrared receptors is unlikely. Their projection
      pattern and other morphological features indicate that the neurons convey
      information about an internal physiological parameter directly into a special
      brain neuropile. We discuss their possible function as thermoreceptors.

PMID- 24015903
TI  - Human (alpha2->6) and avian (alpha2->3) sialylated receptors of influenza A virus
      show distinct conformations and dynamics in solution.
AB  - Differential interactions between influenza A virus protein hemagglutinin (HA)
      and alpha2->3 (avian) or alpha2->6 (human) sialylated glycan receptors play an
      important role in governing host specificity and adaptation of the virus.
      Previous analysis of HA-glycan interactions with trisaccharides showed that, in
      addition to the terminal sialic acid linkage, the conformation and topology of
      the glycans, while they are bound to HA, are key factors in regulating these
      interactions. Here, the solution conformation and dynamics of two representative
      avian and human glycan pentasaccharide receptors [LSTa, Neu5Ac-alpha(2->3)-Gal
      beta(1->3)-GlcNAc-beta(1->3)-Gal-beta(1->4)-Glc; LSTc, (Neu5Ac-alpha(2->6)-Gal
      beta(1->4)-GlcNAc-beta(1->3)-Gal-beta(1->4)-Glc] have been explored using nuclear
      magnetic resonance and molecular dynamics simulation. Analyses demonstrate that,
      in solution, human and avian receptors sample distinct conformations, topologies,
      and dynamics. These unique features of avian and human receptors in solution
      could represent distinct molecular characteristics for recognition by HA, thereby
      providing the HA-glycan interaction specificity in influenza. 

PMID- 24015905
TI  - Interaction mechanism between hydrophobic and hydrophilic surfaces: using
      polystyrene and mica as a model system.
AB  - The interactions between hydrophobic and hydrophilic molecules, particles, or
      surfaces occur in many biological phenomena and industrial processes. In this
      work, polystyrene (PS) and mica were chosen as a model system to investigate the
      interaction mechanism between hydrophilic and hydrophobic surfaces. Using a
      surface forces apparatus (SFA) coupled with a top-view optical microscope,
      interaction forces between PS and mica surfaces were directly probed in five
      different electrolyte solutions (i.e., NaCl, CaCl2, NaOH, HCl, and CH3COOH) of
      various concentrations. Long-range repulsion was observed in low electrolyte
      concentration (e.g., 0.001 M) which was mainly due to the presence of microscopic
      and submicroscopic bubbles on PS surface. A modified Derjaguin-Landau-Verwey
      Overbeek (DLVO) theory well fits the interaction forces by taking into account
      the effect of bubbles on PS surface. The range of the repulsion was dramatically
      reduced in 1.0 M solutions of NaCl, CaCl2, and NaOH but did not significantly
      change in 1.0 M HCl and CH3COOH, which was due to ion specificity effect on the
      formation and stability of bubbles on PS surface. The range of repulsion was also
      significantly reduced to <20 nm in degassed electrolyte solutions. UV-ozone
      treatment changed the hydrophobic attraction of the untreated PS-PS system to
      pure repulsion between untreated PS and treated PS, demonstrating the important
      role of surface hydrophobicity on the formation and stability of bubbles on
      substrates. Our results indicate that DLVO forces dominate the interaction
      between hydrophilic surface (i.e., mica) and hydrophobic polymer (i.e., PS),
      while the types of electrolytes (ion specificity), electrolyte concentration,
      degassing, and surface hydrophobicity can significantly affect the formation and
      stability of bubbles on the interacting surfaces, thus affecting the range and
      magnitude of the interaction forces. 

PMID- 24015904
TI  - Tall fescue endophyte effects on tolerance to water-deficit stress.
AB  - BACKGROUND: The endophytic fungus, Neotyphodium coenophialum, can enhance drought
      tolerance of its host grass, tall fescue. To investigate endophyte effects on
      plant responses to acute water deficit stress, we did comprehensive profiling of
      plant metabolite levels in both shoot and root tissues of genetically identical
      clone pairs of tall fescue with endophyte (E+) and without endophyte (E-) in
      response to direct water deficit stress. The E- clones were generated by treating
      E+ plants with fungicide and selectively propagating single tillers. In time
      course studies on the E+ and E- clones, water was withheld from 0 to 5 days,
      during which levels of free sugars, sugar alcohols, and amino acids were
      determined, as were levels of some major fungal metabolites. RESULTS: After 2-3
      days of withholding water, survival and tillering of re-watered plants was
      significantly greater for E+ than E- clones. Within two to three days of
      withholding water, significant endophyte effects on metabolites manifested as
      higher levels of free glucose, fructose, trehalose, sugar alcohols, proline and
      glutamic acid in shoots and roots. The fungal metabolites, mannitol and loline
      alkaloids, also significantly increased with water deficit. CONCLUSIONS: Our
      results suggest that symbiotic N. coenophialum aids in survival and recovery of
      tall fescue plants from water deficit, and acts in part by inducing rapid
      accumulation of these compatible solutes soon after imposition of stress.

PMID- 24015906
TI  - Iron(III)-based metal-organic frameworks as visible light photocatalysts.
AB  - Herein, a new group of visible light photocatalysts is described. Iron(III)
      oxides could be promising visible light photocatalysts because of their small
      band gap enabling visible light excitation. However, the high electron-hole
      recombination rate limits the yield of highly oxidizing species. This can be
      overcome by reducing the particle dimensions. In this study, metal-organic
      frameworks (MOFs), containing Fe3-MU3-oxo clusters, are proposed as visible light
      photocatalysts. Their photocatalytic performance is tested and proven via the
      degradation of Rhodamine 6G in aqueous solution. For the first time, the
      remarkable photocatalytic efficiency of such Fe(III)-based MOFs under visible
      light illumination (350 up to 850 nm) is shown. 

PMID- 24015907
TI  - Sleep restriction and degraded reaction-time performance in Figaro solo sailing
      races.
AB  - In solo offshore sailing races like those of the Solitaire du Figaro, sleep must
      be obtained in multiple short bouts to maintain competitive performance and
      safety. Little is known about the amount of sleep restriction experienced at sea
      and the effects that fatigue from sleep loss have on sailors' performance.
      Therefore, we assessed sleep in sailors of yachts in the Figaro 2 Beneteau class
      during races and compared response times on a serial simple reaction-time test
      before and after races. Twelve men (professional sailors) recorded their sleep
      and measured their response times during one of the three single-handed races of
      150, 300 and 350 nautical miles (nominally 24-50 h in duration). Total estimated
      sleep duration at sea indicated considerable sleep insufficiency. Response times
      were slower after races than before. The results suggest that professional
      sailors incur severe sleep loss and demonstrate marked performance impairment
      when competing in one- to two-day solo sailing races. Competitive performance
      could be improved by actively managing sleep during solo offshore sailing races.

PMID- 24015908
TI  - Understanding water column and streambed thermal refugia for endangered mussels
      in the Delaware River.
AB  - Groundwater discharge locations along the upper Delaware River, both discrete
      bank seeps and diffuse streambed upwelling, may create thermal niche environments
      that benefit the endangered dwarf wedgemussel (Alasmidonta heterodon). We seek to
      identify whether discrete or diffuse groundwater inflow is the dominant control
      on refugia. Numerous springs and seeps were identified at all locations where
      dwarf wedgemussels still can be found. Infrared imagery and custom high spatial
      resolution fiber-optic distributed temperature sensors reveal complex thermal
      dynamics at one of the seeps with a relatively stable, cold groundwater plume
      extending along the streambed/water-column interface during midsummer. This
      plume, primarily fed by a discrete bank seep, was shown through analytical and
      numerical heat-transport modeling to dominate temperature dynamics in the region
      of potential habitation by the adult dwarf wedgemussel. 

PMID- 24015909
TI  - Impact of coexposure on toluene biomarkers in rats.
AB  - 1. Toluene (TOL) is widely used in industry. Occupational exposure to TOL is
      commonly assessed using TOL in blood, hippuric acid and ortho-cresol. Levels of
      these biomarkers may depend on factors potentially interfering with TOL
      biotransformation, such as the presence of other solvents in the workplace.
      Mercapturic acids (MAs) could be an alternative to the "traditional" TOL
      biomarkers. 2. This study aims (1) to investigate in rat the effects of an
      exposure to vapours mixtures on the TOL metabolism, and (2) to assess how well
      MAs performed in these contexts compared to the traditional TOL biomarkers. 3.
      Rats were exposed by inhalation to binary mixtures of TOL with n-butanol (BuOH),
      ethyl acetate (EtAc), methyl ethyl ketone (MEK) or xylenes (XYLs); biological
      exposure indicators were then measured. 4. Depending on the compounds in the
      mixture and their concentrations, TOL metabolism was accelerated (with BuOH),
      unchanged (with EtAc) or inhibited (with XYLs and MEK). Inhibition leads to an
      increase in blood TOL concentrations, even at authorized atmospheric
      concentrations, which may potentiate the effect of TOL. 5. MAs excretions are
      little affected by coexposure scenarios, their levels correlating well with
      atmospheric TOL levels. They could thus be suitable bioindicators of atmospheric
      TOL exposure.

PMID- 24015910
TI  - Identification of a new class of glucokinase activators through structure-based
      design.
AB  - Glucose flux through glucokinase (GK) controls insulin release from the pancreas
      in response to high glucose concentrations. Glucose flux through GK also
      contributes to reducing hepatic glucose output. Because many individuals with
      type 2 diabetes appear to have an inadequacy or defect in one or both of these
      processes, compounds that can activate GK may serve as effective treatments for
      type 2 diabetes. Herein we report the identification and initial optimization of
      a novel series of allosteric glucokinase activators (GKAs). We discovered an
      initial thiazolylamino pyridine-based hit that was optimized using a structure
      based design strategy and identified 26 as an early lead. Compound 26
      demonstrated a good balance of in vitro potency and enzyme kinetic parameters and
      demonstrated blood glucose reductions in oral glucose tolerance tests in both
      C57BL/6J mice and high-fat fed Zucker diabetic fatty rats. 

PMID- 24015911
TI  - An organized approach to the localization, mapping, and ablation of outflow tract
      ventricular arrhythmias.
AB  - The outflow tract (OT) regions of the right and left ventricles, common sites of
      origin for idiopathic ventricular arrhythmias (VA), have complex three
      dimensional anatomical relationships. The understanding of in situ or
      "attitudinal" relationships not only informs the electrocardiographic
      interpretation of VA site of origin, but also facilitates their catheter-based
      mapping and ablation strategies. By viewing each patient as his or her own
      "control," the expected changes in ECG morphology (i.e., frontal plane QRS axis
      and precordial transition) between adjacent intracardiac structures (e.g., RVOT
      and aortic root) can be reliably predicted. Successful mapping of OT VAs involve
      a combination of activation and pacemapping guided by fluoroscopy,
      electroanatomical mapping, and intracardiac echocardiography. The purpose of this
      manuscript is to provide a simple, reliable strategy for catheter based mapping
      and ablation of OT VAs. We also discuss 2 specific challenges in OT VA mapping:
      (1) differentiating posterior RVOT from right coronary cusp VA origin; and (2)
      mapping VAs originating from the LV summit.

PMID- 24015912
TI  - Effect of FASN gene on milk yield and milk composition in the Chinese Holstein
      dairy population.
AB  - Fatty acid synthase (FASN) is a multifunctional protein that catalyzes de novo
      synthesis of fatty acids in cells. It plays a key role in the lipid biosynthesis
      as well as in the general metabolism of all living animals. We herein
      investigated polymorphisms of FASN. As a result, six single nucleotide
      polymorphisms (SNPs) were found and then genotyped in 752 Chinese Holstein cows.
      It was found that g.17924A>G was non-synonymous, g.13965 C>T, g.16907 T>C and
      g.18663T>C were synonymous mutations and two other two SNPs, g.8948 C>T
      (ss491228481) and g.14439T>C (rs133498277), were in intronic sequences of the
      gene. All such identified SNPs were found to be associated with milk yield and
      composition traits (P = 0.0441 to <0.0001). Significant additive and allele
      substitution effects were observed for three yield traits at all six loci as well
      (P < 0.05 to <0.01). Complete linkage disequilibrium among the five SNPs, with
      the exception of g.8948 C>T, was observed. 

PMID- 24015913
TI  - Development and usability testing of FOCUS: a smartphone system for self
      management of schizophrenia.
AB  - OBJECTIVE: Mobile Health (mHealth) approaches can support the rehabilitation of
      individuals with psychiatric conditions. In the current article, we describe the
      development of a smartphone illness self-management system for people with
      schizophrenia. METHODS: The research was conducted with consumers and
      practitioners at a community-based rehabilitation agency. Stage 1: 904
      individuals with schizophrenia or schizoaffective disorder completed a survey
      reporting on their current use of mobile devices and interest in mHealth
      services. Eight practitioners completed a survey examining their attitudes and
      expectations from an mHealth intervention, and identified needs and potential
      obstacles. Stage 2: A multidisciplinary team incorporated consumer and
      practitioner input and employed design principles for the development of e
      resources for people with schizophrenia to produce an mHealth intervention. Stage
      3: 12 consumers participated in laboratory usability sessions. They performed
      tasks involved in operating the new system, and provided "think aloud" commentary
      and post-session usability ratings. RESULTS: 570 (63%) of survey respondents
      reported owning a mobile device and many expressed interest in receiving mHealth
      services. Most practitioners believed that consumers could learn to use and would
      benefit from an mHealth intervention. In response, we developed a smartphone
      system that targets medication adherence, mood regulation, sleep, social
      functioning, and coping with symptoms. Usability testing revealed several design
      vulnerabilities, and the system was adapted to address consumer needs and
      preferences accordingly. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Through a
      comprehensive development process, we produced an mHealth illness self-management
      intervention that is likely to be used successfully, and is ready for deployment
      and systemic evaluation in real-world conditions.

PMID- 24015914
TI  - Discovery of an allosteric inhibitor binding site in 3-Oxo-acyl-ACP reductase
      from Pseudomonas aeruginosa.
AB  - 3-Oxo-acyl-acyl carrier protein (ACP) reductase (FabG) plays a key role in the
      bacterial fatty acid synthesis II system in pathogenic microorganisms, which has
      been recognized as a potential drug target. FabG catalyzes reduction of a 3-oxo
      acyl-ACP intermediate during the elongation cycle of fatty acid biosynthesis.
      Here, we report gene deletion experiments that support the essentiality of this
      gene in P. aeruginosa and the identification of a number of small molecule FabG
      inhibitors with IC50 values in the nanomolar to low micromolar range and good
      physicochemical properties. Structural characterization of 16 FabG-inhibitor
      complexes by X-ray crystallography revealed that the compounds bind at a novel
      allosteric site located at the FabG subunit-subunit interface. Inhibitor binding
      relies primarily on hydrophobic interactions, but specific hydrogen bonds are
      also observed. Importantly, the binding cavity is formed upon complex formation
      and therefore would not be recognized by virtual screening approaches. The
      structure analysis further reveals that the inhibitors act by inducing
      conformational changes that propagate to the active site, resulting in a
      displacement of the catalytic triad and the inability to bind NADPH. 

PMID- 24015915
TI  - Rationale, design, and baseline features of a randomized controlled trial to
      assess the effects of statin for the secondary prevention of stroke: the Japan
      Statin Treatment Against Recurrent Stroke (J-STARS).
AB  - BACKGROUND: Although statin therapy is beneficial for preventing first strokes,
      the benefit for recurrent stroke and its sub-types remains unknown in Asian
      populations. The aim of this study is to examine the role of pravastatin in the
      secondary prevention of stroke in Japanese patients. METHODS: This is a
      multicenter, randomized, open-label, parallel group study of patients with
      noncardioembolic ischemic stroke (atherothrombotic infarction, lacunar
      infarction, and infarction of undetermined etiology). All patients were diagnosed
      with hyperlipidemia and with a total cholesterol level between 180 and 240 mg/dl
      at enrollment. Patients in the treatment group receive 10 mg/day of pravastatin,
      and those in the control group receive no statin treatment. The primary end-point
      is the recurrence of stroke, including transient ischemic attack. The secondary
      end-points include the onset of respective stroke sub-types and functional
      outcomes related to stroke. The patients were enrolled for five-years and will be
      followed up for five-years. RESULTS: A total of 1578 eligible patients (age: 66.2
      years, men: 68.8%), including 64.2% with lacunar infarction, 25.4% with
      atherothrombotic infarction, and 10.4% with infarction of undetermined etiology
      were included in this study. Lipid levels were generally well controlled (total
      cholesterol: 210.0 mg/dl, low density lipoprotein cholesterol: 129.5 mg/dl) at
      baseline. In addition, the disability of patients was relatively mild, and
      cognitive function was preserved in the majority of patients. CONCLUSION: This
      article reports the rationale, design, and baseline features of a randomized
      controlled trial to assess the effects of statin for the secondary prevention of
      stroke. Follow-ups of patients are in progress and will end in 2014.

PMID- 24015917
TI  - Diverging trends in educational inequalities in cancer mortality between men and
      women in the 2000s in France.
AB  - BACKGROUND: Socioeconomic inequalities in cancer mortality have been observed in
      different European countries and the US until the end of the 1990s, with changes
      over time in the magnitude of these inequalities and contrasted situations
      between countries. The aim of this study is to estimate relative and absolute
      educational differences in cancer mortality in France between 1999 and 2007, and
      to compare these inequalities with those reported during the 1990s. METHODS: Data
      from a representative sample including 1% of the French population were analysed.
      Educational differences among people aged 30-74 were quantified with hazard
      ratios and relative indices of inequality (RII) computed using Cox regression
      models as well as mortality rate difference and population attributable fraction.
      RESULTS: In the period 1999-2007, large relative inequalities were found among
      men for total cancer and smoking and/or alcohol related cancers mortality (lung,
      head and neck, oesophagus). Among women, educational differences were reported
      for total cancer, head and neck and uterus cancer mortality. No association was
      found between education and breast cancer mortality. Slight educational
      differences in colorectal cancer mortality were observed in men and women. For
      most frequent cancers, no change was observed in the magnitude of relative
      inequalities in mortality between the 1990s and the 2000s, although the RII for
      lung cancer increased both in men and women. Among women, a large increase in
      absolute inequalities in mortality was observed for all cancers combined, lung,
      head and neck and colorectal cancer. In contrast, among men, absolute
      inequalities in mortality decreased for all smoking and/or alcohol related
      cancers. CONCLUSION: Although social inequalities in cancer mortality are still
      high among men, an encouraging trend is observed. Among women though, the
      situation regarding social inequalities is less favourable, mainly due to a
      health improvement limited to higher educated women. These inequalities may be
      expected to further increase in future years.

PMID- 24015918
TI  - Role of chicken astrovirus as a causative agent of gout in commercial broilers in
      India.
AB  - Several outbreaks of gout were reported in commercial broilers in India during
      2011 and 2012, causing up to 40% mortality in the birds. Gross and
      histopathological observations confirmed gout. Quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR) analysis from kidney samples of gout-affected
      birds indicated the presence of chicken astrovirus (CAstV) in 41.7% of cases and
      a mixed infection of CAstV and avian nephritis virus (ANV) in 36.4% of cases.
      CAstV isolated from gout-affected kidneys by inoculating embryonated specific
      pathogen free (SPF) eggs showed dwarfing in embryos and a cytopathic effect in
      chicken embryo kidney cells. Inoculation of 1-day-old SPF and broiler chicks with
      CAstVs caused gout and mortality between 4 and 10 days post inoculation. Virus
      isolation and qRT-PCR analysis showed the presence of only CAstV in inoculated
      chicks. Sequence analysis of capsid genes indicated a major group of Indian
      CAstVs that displayed 92.0 to 99.2% intergroup amino acid identity and 83.9 to
      90.4% identity with subgroup Bi CAstVs of UK origin. We designated this group
      Indian Bi. Analysis of the partial polymerase amino acid sequences of our
      isolates indicated two groups of CAstVs (Indian 1 and 2) that displayed 90.2 to
      95.5% amino acid identity between them. We thus report for the first time that,
      in addition to infectious bronchitis virus and ANV, CAstVs are a causative agent
      of gout.

PMID- 24015919
TI  - Atropisomerism of the Asn alpha radicals revealed by Ramachandran surface
      topology.
AB  - C radicals are typically trigonal planar and thus achiral, regardless of whether
      they originate from a chiral or an achiral C-atom (e.g., C-H + (*)OH -> C* +
      H2O). Oxidative stress could initiate radical formation in proteins when, for
      example, the H-atom is abstracted from the Calpha-carbon of an amino acid
      residue. Electronic structure calculations show that such a radical remains
      achiral when formed from the achiral Gly, or the chiral but small Ala residues.
      However, when longer side-chain containing proteogenic amino acid residues are
      studied (e.g., Asn), they provide radicals of axis chirality, which in turn leads
      to atropisomerism observed for the first time for peptides. The two enantiomeric
      extended backbone structures, *betaL and *betaD, interconvert via a pair of
      enantiotopic reaction paths, monitored on a 4D Ramachandran surface, with two
      distinct transition states of very different Gibbs-free energies: 37.4 and 67.7
      kJ/mol, respectively. This discovery requires the reassessment of our
      understanding on radical formation and their conformational and stereochemical
      behavior. Furthermore, the atropisomerism of proteogenic amino acid residues
      should affect our understanding on radicals in biological systems and, thus,
      reframes the role of the D-residues as markers of molecular aging. 

PMID- 24015920
TI  - Mortality and morbidity of very preterm infants in Romania: how are we doing?
AB  - BACKGROUND: Birth before 28 weeks of gestation is associated with high mortality
      and morbidity. The purpose of this study was to examine characteristics
      associated with in-hospital mortality and morbidity among extremely low
      birthweight neonates admitted to three tertiary care centers in Romania. METHODS:
      The study was conducted in three Romanian hospitals with level-III neonatal
      intensive care units. We studied singleton live births at the established
      Romanian limit of viability (i.e., 25-28 weeks' gestational age) born between
      January 2007 and December 2010 (n = 227). Infants born in non-level-III
      facilities transferred to these three centers were included in our study (n =
      39). Descriptive and multivariate statistical analyses were used to describe the
      population and examine outcomes and risk factors. RESULTS: During the study
      period, 62 neonates (27.3%) were delivered at 25 weeks, 56 (24.7%) were delivered
      at 26 weeks, 56 (24.7%) at 27 weeks, and 53 (23.3%) at 28 weeks. Overall in
      hospital mortality was 65% (from 85% at 25 weeks to 35% at 28 weeks). The rates
      for major morbidities were necrotizing enterocolitis 8.8%, bronchopulmonary
      dysplasia 12.5%, and retinopathy of prematurity (stage higher than 2) 26.2%.
      CONCLUSIONS: During 2007-2010, in-hospital survival of infants admitted to three
      neonatal intensive care units in Romania was 35% and ranged from 14% at 25 weeks
      to 64% at 28 weeks.

PMID- 24015921
TI  - Age-related differences in working memory: ERPs reveal age-related delays in
      selection- and inhibition-related processes.
AB  - Faulty inhibition is implicated in age-related working memory decline. ERP signs
      of selection and inhibition of items in working memory (WM) are, respectively, a
      cue-locked parietal positivity (~ 350 ms) and a probe-locked frontal negativity
      (~ 520 ms). To determine when in the older age range differences in selective and
      inhibitory processes might occur, ERPs were recorded in a WM task from 20 young
      (20-28), 20 young-old (60-70), and 20 old-old (71-82) adults. A 4-digit display
      was followed by a cue indicating which 2 of 4 digits were relevant. Proactive
      interference (PI), the reaction time difference between a matching and non
      matching to-be-ignored digit was larger, relative to the young, in both older
      groups. Compared to the young, both the cue- and probe-locked activities were
      prolonged in the older groups. Although there were no topographic differences
      among the age groups, the prolonged PI and associated ERPs suggest a relative age
      related deficit in inhibition.

PMID- 24015922
TI  - Differential cellular gene expression in duck trachea infected with a highly or
      low pathogenic H5N1 avian influenza virus.
AB  - BACKGROUND: Avian influenza A (AI) viruses of subtypes H5 can cause serious
      disease outbreaks in poultry including panzootic due to H5N1 highly pathogenic
      (HP) viruses. These viruses are a threat not only for animal health but also
      public health due to their zoonotic potential. The domestic duck plays a major
      role in the epidemiological cycle of influenza virus subtypes H5 but little is
      known concerning host/pathogen interactions during influenza infection in duck
      species. In this study, a subtracted library from duck trachea (a primary site of
      influenza virus infection) was constructed to analyse and compare the host
      response after a highly or low pathogenic (LP) H5N1-infection. RESULTS: Here, we
      show that more than 200 different genes were differentially expressed in infected
      duck trachea to a significant degree. In addition, significant differentially
      expressed genes between LPAI- and HPAI-infected tracheas were observed. Gene
      ontology annotation was used and specific signalling pathways were identified.
      These pathways were different for LPAI and HPAI-infected tracheas, except for the
      CXCR4 signalling pathway which is implicated in immune response. A different
      modulation of genes in the CXCR4 signalling pathway and TRIM33 was induced in
      duck tracheas infected with a HPAI- or a LPAI-H5N1. CONCLUSION: First, this study
      indicates that Suppressive Subtractive Hybridization (SSH) is an alternative
      approach to gain insights into the pathogenesis of influenza infection in ducks.
      Secondly, the results indicate that cellular gene expression in the duck trachea
      was differently modulated after infection with a LPAI-H5N1 or after infection
      with a HPAI-H5N1 virus. Such difference found in infected trachea, a primary
      infection site, could precede continuation of infection and could explain
      appearance of respiratory symptoms or not.

PMID- 24015923
TI  - Shouldn't it be simpler than that?

PMID- 24015925
TI  - Functional characterization of a serine-threonine protein kinase from Bambusa
      balcooa that implicates in cellulose overproduction and superior quality fiber
      formation.
AB  - BACKGROUND: Molecular markers allow rapid identification of biologically
      important germplasm/s having desired character. Previously we have reported a
      genotype specific molecular marker, Balco1128 [GenBank ID EU258678] of Bambusa
      balcooa containing an ORF (375 bp) having high similarity with receptor like
      cytoplasmic kinase of Arabidopsis and Oryza. Balco1128 was found to be associated
      only with bamboo genotypes endowed with high cellulose and low lignin contents of
      fibers. Under the above backdrop, it was necessitated to characterize this
      genetic marker for better understanding of its biological significance in context
      of superior quality fiber development. RESULTS: The full length cDNA (3342 bp) of
      BbKst, a serine-threonine protein kinase was isolated from B. balcooa comprising
      of six LRR domains at the N-terminal end and a kinase domain at the C-terminal
      end. Bacteria-expressed BbKst-kinase domain (3339 bp long) showed Mg(2+)
      dependent kinase activity at pH 7.0, 28 degrees C. Bioinformatics study followed
      by phospho-amino analysis further confirmed that BbKst-kinase belongs to the
      serine/threonine protein kinase family. Transcript analysis of the BbKst gene
      following RNA slot blot hybridization and qPCR revealed higher expression of
      BbKst during initiation and elongation stages of fiber development. Tissue
      specific expression studies showed much higher expression of BbKst transcript in
      stems and internodes of B. balcooa than in leaves and rhizomes. Southern analysis
      revealed single copy insertion of BbKst in most of the Agrobacterium mediated
      transgenic tobacco plants. Real-time PCR detected 150-200 fold enhanced
      expression of BbKst in different T1 tobacco lines than that of the vector
      transformed plants. Heterologous expression of BbKst under control of 35S
      promoter in transgenic tobacco showed high cellulose deposition in the xylem
      fibers. Number of xylary fibers was higher in transgenic T0 and T1 plants than
      that of empty-vector transformed tobacco plants offering enhanced mechanical
      strength to the transgenic plants, which was also substantiated by their strong
      upright phenotypes, significantly higher cellulose contents, flexibility
      coefficient, slenderness ratio, and lower Runkel ratio of the fibers.
      CONCLUSIONS: This finding clearly demonstrated that BbKst gene (GenBank ID
      JQ432560) encodes a serine/threonine protein kinase. BbKst induced higher
      cellulose deposition/synthesis in transgenic tobacco plants, an important
      attribute of fiber quality bestowing additional strength to the plant.

PMID- 24015924
TI  - Bacterial actins and their diversity.
AB  - For many years, bacteria were considered rather simple organisms, but the
      dogmatic notion that subcellular organization is a eukaryotic trait has been
      overthrown for more than a decade. The discovery of homologues of the eukaryotic
      cytoskeletal proteins actin, tubulin, and intermediate filaments in bacteria has
      been instrumental in changing this view. Over the past few years, we have gained
      an incredible level of insight into the diverse family of bacterial actins and
      their molecular workings. Here we review the functional, biochemical, and
      structural features of the most well-studied bacterial actins. 

PMID- 24015926
TI  - Influence of cationic surfactants on the formation and surface oxidation states
      of gold nanoparticles produced via laser ablation.
AB  - We report on the time evolution of gold nanoparticles produced by laser ablation
      in the presence of the cationic surfactants cetyltrimethylammonium bromide (CTAB)
      and cetyltrimethylammonium chloride (CTAC) in aqueous solution. The broader
      applicability of a laser-induced nanoparticle formation kinetic model previously
      developed by us for the case of anionic surfactants in aqueous solution [ J.
      Phys. Chem. C 2010 , 114 , 15931 - 15940 ] is shown to also apply in the presence
      of cationic surfactants. We explore the surface properties of the nanoparticles
      produced in the presence of the cationic surfactants via synchrotron X-ray
      photoelectron spectroscopy (XPS). The XPS data indicate that at CTA(+)
      concentrations approximating the aqueous critical micelle concentration Au(III)
      is present on the nanoparticle surface. Such oxidation is not observed at (i)
      lower CTA(+) concentrations, (ii) in the presence of an anionic surfactant, or
      (iii) in the case of pure water as a solvent. 

PMID- 24015928
TI  - Determination of the exercise intensity that elicits maximal fat oxidation in
      short-time testing.
AB  - Maximal fat oxidation (MFO) rate and the exercise intensity that elicits MFO
      (FATmax-intensity) were designed to evaluate fat metabolism capacity and to
      provide individuals with a target exercise intensity during prolonged exercise.
      However, the previous methods of determining FATmax-intensity were time
      consuming. The purpose of this study was to examine the validity of FATmax
      intensity determined by short-time testing. Nine healthy young men performed ramp
      exercise, in a short-time test, until exhaustion and 5 constant-load exercises of
      60 min each at individual FATmax-intensity determined by ramp protocol (FATmax
      intensity(R)), FATmax-intensity(R) +/- 5% of peak oxygen uptake (VO2peak) and
      FATmax-intensity(R) +/- 10%VO2peak. FATmax-intensity was determined among 5
      trials at points of early exercise (10 min) and prolonged exercise (60 min) to
      evaluate the validity of FATmax-intensity(R). Ten minutes after starting constant
      load exercise, FATmax-intensity(R) showed the highest fat oxidation among 5
      trials, even though MFO by ramp protocol was overestimated. Therefore, it may be
      useful for evaluation of fat metabolism to include the measurement of the FATmax
      intensity in a routine ramp test. However, because FATmax-intensity(R) did not
      elicit the highest fat oxidation among 5 trials of 60 min each after starting
      constant-load exercise, FATmax-intensity(R) may not be effective for prolonged
      exercise training.

PMID- 24015927
TI  - Activation of snap-top capped mesoporous silica nanocontainers using two near
      infrared photons.
AB  - Photoactivation of "snap-top" stoppers over the pore openings of mesoporous
      silica nanoparticles releases intact cargo molecules from the pores. The on
      command release can be stimulated by either one UV photon or two coherent near-IR
      photons. Two-photon activation is particularly desirable for use in biological
      systems because it enables good tissue penetration and precise spatial control.
      Stoppers were assembled by first binding photolabile coumarin-based molecules to
      the nanoparticle surface. Then, after the particles were loaded with cargo, bulky
      beta-cyclodextrin (CD) molecules were noncovalently associated with the
      substituted coumarin molecule, blocking the pores and preventing the cargo from
      escaping. One-photon excitation at 376 nm or two-photon excitation at 800 nm
      cleaves the bond holding the coumarin to the nanopore, releasing both the CD cap
      and the cargo. The dynamics of both the cleavage of the cap and the cargo release
      was monitored using fluorescence spectroscopy. This system traps intact cargo
      molecules without the necessity of chemical modification, releases them with
      tissue-penetrating near-IR light, and has possible applications in
      photostimulated drug delivery. 

PMID- 24015929
TI  - Effects of varying growth conditions on stable carbon isotope fractionation of
      trichloroethene (TCE) by tceA-containing Dehalococcoides mccartyi strains.
AB  - To quantify in situ bioremediation using compound specific isotope analysis
      (CSIA), isotope fractionation data obtained from the field is interpreted
      according to laboratory-derived enrichment factors. Although previous studies
      that have quantified dynamic isotopic shifts during the reductive dechlorination
      of trichloroethene (TCE) indicate that fractionation factors can be highly
      variable from culture-to-culture and site-to-site, the effects of growth
      condition on the isotope fractionation during reductive dechlorination have not
      been previously examined. Here, carbon isotope fractionation by Dehalococcoides
      mccartyi 195 (Dhc195) maintained under a variety of growth conditions was
      examined. Enrichment factors quantified when Dhc195 was subjected to four
      suboptimal growth conditions, including decreased temperature (-13.3 +/-
      0.90/00), trace vitamin B12 availability (-12.7 +/- 1.00/00), limited fixed
      nitrogen (-14.4 +/- 0.80/00), and elevated vinyl chloride exposure (-12.5 +/-
      0.40/00), indicate that the fractionation is similar across a range of tested
      conditions. The TCE enrichment factors for two syntrophic cocultures, Dhc195 with
      Desulfovibrio vulgaris Hildenborough (-13.0 +/- 2.00/00) and Dhc195 with
      Syntrophomonas wolfei (-10.4 +/- 1.20/00 and -13.3 +/- 1.00/00), were also
      similar to a control experiment. In order to test the stability of enrichment
      factors in microbial communities, the isotope fractionation was quantified for
      Dhc-containing groundwater communities before and after two-year enrichment
      periods under different growth conditions. Although these enrichment factors (
      8.9 +/- 0.40/00, -6.8 +/- 0.80/00, -8.7 +/- 1.30/00, -9.4 +/- 0.70/00, and -7.2
      +/- 0.30/00) were predominantly outside the range of values quantified for the
      isolate and cocultures, all tested enrichment conditions within the communities
      produced nearly similar fractionations. Enrichment factors were not significantly
      affected by changes in any of the tested growth conditions for the pure cultures,
      cocultures or the mixed communities, indicating that despite a variety of
      temperature, nutrient, and cofactor-limiting conditions, stable carbon isotope
      fractionations remain consistent for given Dehalococcoides cultures. 

PMID- 24015930
TI  - High risk accessory pathway ablation inside a large coronary sinus diverticulum
      in a patient with coexistent drug-induced type 1 Brugada ECG pattern.

PMID- 24015931
TI  - Public health nurses' conceptions of their role related to families with a child
      having attention-deficit/hyperactivity disorder.
AB  - Attention-deficit/hyperactivity disorder is one of the most common behavioural
      disorders diagnosed in children. Children who have this disorder have
      difficulties regarding regulation of their emotions, maintaining attention and
      impulse control. Parents may need guidance in creating structure and predictable
      boundaries. One of the personnel who meet these families is the public health
      nurse. The aim of this study was to explore the public health nurses role in
      relation to these families. A qualitative explorative design with a
      phenomenographic approach was used. Interviews were performed with 19 nurses, six
      in group and one individual. In the data analyses, three descriptive categories
      emerged: 'supporting the family-unit', which describes the nurses supervising the
      parents and the child in everyday challenges; 'understanding the child', which
      describes how the public health nurses use professional competence and choose the
      time and arena to observe the child and; 'collaborating multidisciplinary', which
      describes how the public health nurses define their own role and conceive their
      collaboration with other professionals. The public health nurse (PHN)'s support
      for the parents and the entire family is important, and the PHN is the first
      encounter and trustful follower throughout the course of diagnosis and care. 

PMID- 24015933
TI  - Change in heat capacity for enzyme catalysis determines temperature dependence of
      enzyme catalyzed rates.
AB  - The increase in enzymatic rates with temperature up to an optimum temperature
      (Topt) is widely attributed to classical Arrhenius behavior, with the decrease in
      enzymatic rates above Topt ascribed to protein denaturation and/or aggregation.
      This account persists despite many investigators noting that denaturation is
      insufficient to explain the decline in enzymatic rates above Topt. Here we show
      that it is the change in heat capacity associated with enzyme catalysis
      (DeltaC(?)p) and its effect on the temperature dependence of DeltaG(?) that
      determines the temperature dependence of enzyme activity. Through mutagenesis, we
      demonstrate that the Topt of an enzyme is correlated with DeltaC(?)p and that
      changes to DeltaC(?)p are sufficient to change Topt without affecting the
      catalytic rate. Furthermore, using X-ray crystallography and molecular dynamics
      simulations we reveal the molecular details underpinning these changes in
      DeltaC(?)p. The influence of DeltaC(?)p on enzymatic rates has implications for
      the temperature dependence of biological rates from enzymes to ecosystems. 

PMID- 24015932
TI  - Berberine potently attenuates intestinal polyps growth in ApcMin mice and
      familial adenomatous polyposis patients through inhibition of Wnt signalling.
AB  - As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine
      has been recently reported to exhibit anti-tumour effects against a wide spectrum
      of cancer. However, the mechanism was largely unknown. Gene chip array reveals
      that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down
      regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling.
      TOPflash analysis revealed that Wnt activity was significantly reduced after
      berberine treatment, and the mechanism of which might be that berberine disrupted
      beta-catenin transfer to nucleus through up-regulating the expression of
      adenomatous polyposis coli (APC) gene and stabilized APC-beta-catenin complex.
      Berberine administration in ApcMin/+ mice exhibited fewer and smaller polyps in
      intestine, along with reduction in cyclin D1 and c-Myc expression. In clinical
      practice, oral administration of berberine also significantly reduced the
      familial adenomatous polyposis patients' polyp size along with the inhibition of
      cyclin D1 expression in polyp samples. These observations indicate that berberine
      inhibits colon tumour formation through inhibition of Wnt/beta-catenin signalling
      and berberine might be a promising drug for the prevention of colon cancer. 

PMID- 24015934
TI  - Randomized, multicenter, comparative study of NEURO versus CIMT in poststroke
      patients with upper limb hemiparesis: the NEURO-VERIFY Study.
AB  - BACKGROUND: Many poststroke patients suffer functional motor limitation of the
      affected upper limb, which is associated with diminished health-related quality
      of life. AIMS: The aim of this study is to conduct a randomized, multicenter,
      comparative study of low-frequency repetitive transcranial magnetic stimulation
      combined with intensive occupational therapy, NEURO (NovEl intervention Using
      Repetitive TMS and intensive Occupational therapy) versus constraint-induced
      movement therapy in poststroke patients with upper limb hemiparesis. METHODS: In
      this randomized controlled study of NEURO and constraint-induced movement
      therapy, 66 poststroke patients with upper limb hemiparesis were randomly
      assigned at 2:1 ratio to low-frequency repetitive transcranial magnetic
      stimulation plus occupational therapy (NEURO group) or constraint-induced
      movement therapy (constraint-induced movement therapy group) for 15 days. Fugl
      Meyer Assessment and Wolf Motor Function Test and Functional Ability Score of
      Wolf Motor Function Test were used for assessment. RESULTS: No differences in
      patients' characteristics were found between the two groups at baseline. The Fugl
      Meyer Assessment score was significantly higher in both groups after the 15-day
      treatment compared with the baseline. Changes in Fugl-Meyer Assessment scores and
      Functional Ability Score of Wolf Motor Function Test were significantly higher in
      the NEURO group than in the constraint-induced movement therapy group, whereas
      the decrease in the Wolf Motor Function Test log performance time was comparable
      between the two groups (changes in Fugl-Meyer Assessment score, NEURO: 5.39 +/-
      4.28, constraint-induced movement therapy: 3.09 +/- 4.50 points; mean +/-
      standard error of the mean; P < 0.05) (changes in Functional Ability Score of
      Wolf Motor Function Test, NEURO: 3.98 +/- 2.99, constraint-induced movement
      therapy: 2.09 +/- 2.96 points; P < 0.05). CONCLUSIONS: The results of the 15-day
      rehabilitative protocol showed the superiority of NEURO relative to constraint
      induced movement therapy; NEURO improved the motion of the whole upper limb and
      resulted in functional improvement in activities of daily living.

PMID- 24015935
TI  - Magnesium status and the physical performance of volleyball players: effects of
      magnesium supplementation.
AB  - The aim of this study was to test the hypothesis that magnesium supplementation
      influences the physical performance of volleyball players, as the efficacy of
      this approach remains questionable. Twenty-five professional male volleyball
      players were assigned randomly to experimental (350 mg Mg . d(-1), 4 weeks) and
      control groups (500 mg maltodextrin . d(-1), 4 weeks) maintaining inter-group
      homogeneity of urinary magnesium. Erythrocyte, plasma and urinary magnesium
      levels, plasma creatine kinase activity, lactate production, maximal oxygen
      uptake (VO2 max) and plyometric (squat jump, countermovement jump,
      countermovement jump with arm swing) and isokinetic (peak torque, potency and
      total work) performances were evaluated before (T0) and after (T1)
      supplementation. Levels of erythrocyte and urinary magnesium and creatine kinase
      activity and VO2 max remained within normal ranges in both groups. Plasma
      magnesium decreased significantly only within the experimental group. Significant
      decreases in lactate production and significant increases (of up to 3 cm) in
      countermovement jump and countermovement jump with arm swing values were detected
      in the experimental group following magnesium supplementation, but not in the
      control group at T1. It is concluded that magnesium supplementation improved
      alactic anaerobic metabolism, even though the players were not magnesium
      deficient.

PMID- 24015936
TI  - Erythropoiesis-stimulating agents: friends or foes?

PMID- 24015937
TI  - Plasma products and prion removal: "Is you is or is you ain't ...?".

PMID- 24015938
TI  - Transfusion medicine illustrated: Mosaic Trisomy 9 in an infant with mixed-field
      ABO blood grouping.

PMID- 24015939
TI  - Hepatitis A virus strain KRM238 resistant at heat inactivation.

PMID- 24015940
TI  - In reply.

PMID- 24015941
TI  - Posttransfusion thrombocytopenia: a cautionary tale of female group AB plasma.

PMID- 24015942
TI  - Processed residual pump blood using ultrafiltration during cardiovascular
      surgery.

PMID- 24015943
TI  - Processing residual pump blood using ultrafiltration during cardiovascular
      surgery.

PMID- 24015944
TI  - Rapid mobilization of fully functional natural killer cells into blood by
      AMD3100.

PMID- 24015945
TI  - Ketamine and atropine decrease pain for preterm newborn tracheal intubation in
      the delivery room: an observational pilot study.
AB  - AIM: Various analgesic strategies are used before tracheal intubation of preterm
      newborns in the delivery room, due to the lack of a standard protocol and
      difficult venous access. This study evaluated the feasibility and efficacy of
      short venous catheter insertion and immediate ketamine analgesia for tracheal
      intubation of preterm newborns at birth in the delivery room. METHODS:
      Prospective observational pilot study, with ketamine and atropine used at the
      paediatrician's discretion. Pain score, heart rate, SpO2 nadirs, procedure
      duration and neonatal intensive care unit morbidity were recorded. RESULTS: Fifty
      seven consecutive preterm newborns were included between January I and June 30,
      2012: 15 in the no analgesia group and 39 in the intravenous ketamine group.
      Short catheter insertion failed in three newborns. The pain score was lower
      during laryngoscopy in the ketamine group (4 +/- 0.7 vs. 2.9 +/- 3.2 in the no
      analgesia group, p < 0.001). The heart rate nadir during tracheal intubation was
      150.7 +/- 29.6 bpm (vs. 112.6 +/- 35.5 bpm in the no analgesia group, p < 0.01).
      Surfactant therapy was administered to 79.5% of newborns in the ketamine group
      (vs. 92.3%, p = 0.29) in the first 30 min of life. CONCLUSION: Short venous
      catheter insertion with immediate ketamine analgesia plus atropine for tracheal
      intubation of preterm newborns in the delivery room was effective in decreasing
      pain and preventing vagal bradycardia.

PMID- 24015946
TI  - Fate of Arsenate adsorbed on Nano-TiO2 in the presence of sulfate reducing
      bacteria.
AB  - Arsenic removal using nanomaterials has attracted increasing attention worldwide,
      whereas the potential release of As from spent nanomaterials to groundwater in
      reducing environments is presently underappreciated. This research investigated
      the fate of As(V) adsorbed on nano-TiO2 in the presence of sulfate reducing
      bacteria (SRB) Desulfovibrio vulgaris strains DP4 and ATCC 7757. The incubation
      results demonstrated that As(V) was desorbed from nano TiO2, and subsequently
      reduced to As(III) in aqueous solution. The release of adsorbed As(V) was two to
      three times higher in biotic samples than that in abiotic controls. Reduction of
      As(V) to As(III) in biotic samples was coupled with the conversion of sulfate to
      sulfide, while no As(III) was observed in abiotic controls. STXM results provided
      the direct evidence of appreciable As(III) and As(V) on TiO2. XANES analysis
      indicated that As(V) was the predominant species for three As loads of 150, 300,
      and 5700 mg/g, whereas 15-28% As precipitated as orpiment for a high As load of
      5700 mg/g. In spite of orpiment formation, As mobilized in higher amounts in the
      SRB presence than in abiotic controls, highlighting the key role of SRB in the
      fate of As in the presence of nanomaterials. 

PMID- 24015947
TI  - Stereoselective synthesis of five-membered spirooxindoles through Tomita zipper
      cyclization.
AB  - Functionalized five-membered spirooxindoles were furnished in good yields and
      excellent stereoselectivities by using an effective Tomita zipper cyclization
      (TZC) reaction through organophosphine catalysis. 

PMID- 24015948
TI  - Mechanical stability of the antibody domain CH3 homodimer in different oxidation
      states.
AB  - The CH3 homodimer at the C-terminal end of the antibody heavy chain is the key
      noncovalent interaction stabilizing antibody proteins. Here, we use single
      molecule force spectroscopy to investigate the dissociation mechanics of CH3 as a
      proxy for antibody mechanical stability. We find the CH3 homodimer to be a highly
      stable complex, and its dissociation force of >150 pN at a loading rate of ~5500
      pN/s exceeds the stability of most protein-protein interactions studied to date.
      Separated CH3 monomers, on the other hand, are mechanically labile and only short
      lived. Each CH3 monomer contains a conserved buried disulfide bridge, and we find
      that the successive reduction of one or both disulfide bridges in the dimer
      results in a stepwise decrease of the dissociation force. This suggests a
      structural role of the disulfide bridges helping to mold the high-affinity domain
      domain interface, even though they are neither required for nor directly involved
      in dimerization. Taken together, our results set a limit on how much force a
      single antibody can bear and reveal the CH3 homodimer as a mechanical fastener
      that prevents antibody dissociation. 

PMID- 24015949
TI  - The size of the labor wards: is bigger better when it comes to patient safety?
AB  - OBJECTIVE: To assess possible associations between the size of labor units and
      the frequency of approved obstetric claims. DESIGN: A nationwide retrospective
      descriptive study. SETTING: Denmark. POPULATION: All patients seeking financial
      compensation due to obstetric injuries occurring between 1995 and 2009. METHODS:
      In all, 1440 anonymized obstetrics claims were reviewed; 1326 were included in
      the study. Information regarding the annual number of deliveries for each place
      of injury was retrieved from the National Birth Registry. MAIN OUTCOME MEASURES:
      Obstetric injuries approved by the Danish Patient Insurance Association
      categorized by labor unit size. RESULTS: The overall approval rate for submitted
      claims was 39.7%. Large labor units (3000-3999 deliveries/year) were found to
      have a lower approval rate (34.2%), compared with very large (>=4000
      deliveries/year, 38.6%), intermediate (1000-2999 deliveries/year, 41.7%), and
      small (<1000 deliveries/year, 50.0%) units, (p < 0.05). The majority of
      compensation claims were approved with reference to the "specialist rule,"
      assuming that if an experienced specialist had conducted the treatment
      differently the injury could have been avoided. Claims from small units showed a
      trend for being more often based on the specialist rule than seen in larger units
      (p < 0.05, test for trend). CONCLUSION: The results may reflect that large labor
      units are living up to the principle of best practice to a greater degree.
      Several factors can be linked to the size of the labor unit and a better
      availability of in-house obstetricians as well as auxiliary specialists could be
      part of the explanation.

PMID- 24015950
TI  - Intrinsic flexibility of West Nile virus protease in solution characterized using
      small-angle X-ray scattering.
AB  - West Nile virus (WNV) is a mosquito-borne flavivirus with a rapidly expanding
      global distribution. Infection can cause severe neurological disease and fatality
      in humans. Efforts are ongoing to develop antiviral drugs that inhibit the WNV
      protease, a viral enzyme required for polyprotein processing. Unfortunately,
      little is known about the solution structure of recombinant WNV protease (NS2B
      NS3pro) used for antiviral drug discovery and development, although X-ray crystal
      structures and nuclear magnetic resonance (NMR) studies have provided valuable
      insights into the interactions between NS2B-NS3pro and peptide-based inhibitors.
      We completed small-angle X-ray scattering and Fourier transform infrared
      spectroscopy experiments to determine the solution structure and dynamics of WNV
      NS2B-NS3pro in the absence of a bound substrate or inhibitor. Importantly, these
      solution studies suggested that all or most of the NS2B cofactor was highly
      flexible and formed an ensemble of structures, in contrast to the NS2B tertiary
      structures observed in crystallographic and NMR studies. The secondary structure
      of NS2B-NS3pro in solution had high beta-content, similar to the secondary
      structure observed in crystallographic studies. This work provided evidence of
      the intrinsic flexibility and conformational heterogeneity of the NS2B chain of
      the WNV protease in the absence of substratelike ligands, which should be
      considered during antiviral drug discovery and development efforts. 

PMID- 24015951
TI  - On the characterization of inhomogeneity of the density distribution in
      supercritical fluids via molecular dynamics simulation and data mining analysis.
AB  - We combined molecular dynamics simulation and DBSCAN algorithm (Density Based
      Spatial Clustering of Application with Noise) in order to characterize the local
      density inhomogeneity distribution in supercritical fluids. The DBSCAN is an
      algorithm that is capable of finding arbitrarily shaped density domains, where
      domains are defined as dense regions separated by low-density regions. The
      inhomogeneity of density domain distributions of Ar system in sub- and
      supercritical conditions along the 50 bar isobar is associated with the
      occurrence of a maximum in the fluctuation of number of particles of the density
      domains. This maximum coincides with the temperature, Talpha, at which the
      thermal expansion occurs. Furthermore, using Voronoi polyhedral analysis, we
      characterized the structure of the density domains. The results show that with
      increasing temperature below Talpha, the increase of the inhomogeneity is mainly
      associated with the density fluctuation of the border particles of the density
      domains, while with increasing temperature above Talpha, the decrease of the
      inhomogeneity is associated with the core particles. 

PMID- 24015952
TI  - Posterior laryngitis: a disease with different aetiologies affecting health
      related quality of life: a prospective case-control study.
AB  - BACKGROUND: Laryngo-pharyngeal reflux (LPR) is assumed to be the most common
      cause of posterior laryngitis (PL). Since LPR is found in healthy subjects, and
      PL patients are not improved by acid-reducing therapy, other aetiologies to PL
      must be considered. The aims of this study in PL were to investigate the
      prevalence of acid reflux in the proximal oesophagus and functional
      gastrointestinal symptoms, to analyse motilin levels in plasma, and to assess
      health-related quality of life (HRQOL) before and after treatment. METHODS: Forty
      six patients (26 women), with verified PL, median age 55 (IQR 41-68) years, were
      referred to oesophago-gastro-duodenoscopy and 24-h pH monitoring. Plasma motilin
      was analysed. The 36-item Short-Form questionnaire was completed at inclusion and
      at follow-up after 43+/-14 months, when also the Visual Analogue Scale for
      Irritable Bowel Syndrome was completed. Values were compared to controls.
      Treatment and relief of symptoms were noted from medical records. RESULTS: Thirty
      four percent had proximal acid reflux and 40% showed signs of distal reflux.
      Ninety-four percent received acid-reducing treatment, with total relief of
      symptoms in 17%. Patients with reflux symptoms had lower plasma motilin levels
      compared to patients without reflux symptoms (p = 0.021). The HRQOL was impaired
      at inclusion, but improved over time. Patients, especially men, had more
      functional gastrointestinal symptoms than controls. CONCLUSIONS: This study
      indicates that a minority of patients with PL has LPR and is cured by acid
      reducing therapy. Disturbed plasma motilin levels and presence of functional
      gastrointestinal symptoms are found in PL. The impaired HRQOL improves over time.

PMID- 24015953
TI  - Study protocol for a randomized, double-blind, placebo-controlled trial of a
      single preoperative steroid dose to prevent nausea and vomiting after
      thyroidectomy: the tPONV study.
AB  - BACKGROUND: Postoperative nausea and vomiting after general anesthesia is not
      only an unpleasant problem affecting 20-30% of surgical patients but may also
      lead to severe postoperative complications. There is a particularly high
      incidence of postoperative nausea and vomiting following thyroidectomy.
      Dexamethasone has been described as highly effective against chemotherapy-induced
      nausea and vomiting and has been proposed as a first-line method of postoperative
      nausea and vomiting prophylaxis. Despite this possible beneficial effect, the
      prophylactic administration of dexamethasone before surgery to prevent or
      ameliorate postoperative nausea and vomiting has not been established. A
      bilateral superficial cervical plexus block during thyroid surgery under general
      anesthesia significantly reduces pain. Of even greater clinical importance, this
      block prevents the need for postoperative opioids. Therefore, patients undergoing
      thyroidectomy and a bilateral superficial cervical plexus block are an ideal
      group to investigate the efficacy of dexamethasone for postoperative nausea and
      vomiting. These patients have a high incidence of postoperative nausea and
      vomiting and do not require opioids. They have no abdominal surgery, which can
      cause nausea and vomiting via a paralytic ileus. Combined with the highly
      standardized anesthesia protocol in use at our institution, this setting allows
      all known biases to be controlled. METHODS/DESIGN: We will perform a parallel two
      arm, randomized (1:1), double-blind, placebo-controlled, single-center trial.
      Adults (>=18 years) scheduled for primary partial or total thyroidectomy because
      of a benign disease will be eligible for inclusion. The participants will be
      randomized to receive a single, intravenous preoperative dose of either 8 mg of
      dexamethasone in 2 ml saline (treatment group) or saline alone (placebo group).
      All the patients will receive a bilateral superficial cervical plexus block and
      standardized anesthesia. The primary outcome will be the incidence of
      postoperative nausea and vomiting. A total of 152 patients will be recruited,
      providing 80% power to detect a 50% reduction in the incidence of postoperative
      nausea and vomiting. Any patients who require opioid treatment will be excluded
      from the per-protocol analysis. DISCUSSION: In the present protocol, we reduced
      bias to the greatest extent possible. Thus, we expect to definitively clarify the
      efficacy of dexamethasone for postoperative nausea and vomiting prophylaxis.
      TRIAL REGISTRATION: http://www.clinicaltrials.gov: NCT01189292.

PMID- 24015954
TI  - Knowledge matters: how children evaluate the reliability of testimony as a
      process of rational inference.
AB  - Children's causal learning has been characterized as a rational process, in which
      children appropriately evaluate evidence from their observations and actions in
      light of their existing conceptual knowledge. We propose a similar framework for
      children's selective social learning, concentrating on information learned from
      others' testimony. We examine how children use their existing conceptual
      knowledge of the physical and social world to determine the reliability of
      testimony. We describe existing studies that offer both direct and indirect
      support for selective trust as rational inference and discuss how this framework
      may resolve some of the conflicting evidence surrounding cases of indiscriminate
      trust. Importantly, this framework emphasizes that children are active in
      selecting evidence (both social and experiential), rather than being passive
      recipients of knowledge, and motivates further studies that more systematically
      examine the process of learning from social information.

PMID- 24015955
TI  - How do PDP models learn quasiregularity?
AB  - Parallel distributed processing (PDP) models have had a profound impact on the
      study of cognition. One domain in which they have been particularly influential
      is learning quasiregularity, in which mastery requires both learning regularities
      that capture the majority of the structure in the input plus learning exceptions
      that violate the regularities. How PDP models learn quasiregularity is still not
      well understood. Small- and large-scale analyses of a feedforward, 3-layer
      network were carried out to address 2 fundamental issues about network
      functioning: how the model can learn both regularities and exceptions without
      sacrificing generalizability and the nature of the hidden representation that
      makes this learning possible. Results show that capacity-limited learning
      pressures the network to form componential representations, which ensures good
      generalizability. Small and highly local perturbations of this representational
      system allow exceptions to be learned while minimally disrupting
      generalizability. Theoretical and methodological implications of the findings are
      discussed.

PMID- 24015957
TI  - Evaluation of a sex hormone-binding globulin automated chemiluminescent assay.
AB  - BACKGROUND: Sex hormone-binding globulin (SHBG) is the main transport protein of
      sex steroids. This study evaluated the analytical performance of the recently
      developed Access SHBG assay (Beckman Coulter) and compared it with other
      commercial methods for the determination of serum SHBG. Clinical validation was
      also performed. METHODS: Analytical performance including within-run and between
      run imprecision was assessed for Access SHBG assay on the automated Beckman
      UniCel DxI800 analyzer. Linearity was assessed using five dilutions of the serum
      samples. For methods comparison, SHBG levels were determined also with Immulite
      2000 analyzer (Siemens Healthcare) using clinical serum samples (n = 104). For
      clinical validation 135 specimens from healthy subjects, pregnant women,
      hypothyroid and hyperthyroid patients were analyzed. RESULTS: Total coefficients
      of variation were < 5.5%. Linearity test showed > 90% recovery for all samples
      and for all dilution rates. Comparison analysis (Bland-Altman difference analysis
      and Passing-Bablock regression) showed an acceptable agreement between selected
      methods. SHBG values measured by Access SHBG assay in different groups of
      subjects were in agreement with other clinical evidence. CONCLUSIONS: Automated
      Access SHBG assay appears to be a reliable and easy to perform assay, as
      necessary for application in routine diagnostics.

PMID- 24015956
TI  - Discrete-slots models of visual working-memory response times.
AB  - Much recent research has aimed to establish whether visual working memory (WM) is
      better characterized by a limited number of discrete all-or-none slots or by a
      continuous sharing of memory resources. To date, however, researchers have not
      considered the response-time (RT) predictions of discrete-slots versus shared
      resources models. To complement the past research in this field, we formalize a
      family of mixed-state, discrete-slots models for explaining choice and RTs in
      tasks of visual WM change detection. In the tasks under investigation, a small
      set of visual items is presented, followed by a test item in 1 of the studied
      positions for which a change judgment must be made. According to the models, if
      the studied item in that position is retained in 1 of the discrete slots, then a
      memory-based evidence-accumulation process determines the choice and the RT; if
      the studied item in that position is missing, then a guessing-based accumulation
      process operates. Observed RT distributions are therefore theorized to arise as
      probabilistic mixtures of the memory-based and guessing distributions. We
      formalize an analogous set of continuous shared-resources models. The model
      classes are tested on individual subjects with both qualitative contrasts and
      quantitative fits to RT-distribution data. The discrete-slots models provide much
      better qualitative and quantitative accounts of the RT and choice data than do
      the shared-resources models, although there is some evidence for "slots plus
      resources" when memory set size is very small.

PMID- 24015958
TI  - The HER4 isoform JM-a/CYT2 relates to improved survival in bladder cancer
      patients but only if the estrogen receptor alpha is not expressed.
AB  - Bladder cancer tumors expressing human epidermal growth factor receptor 4 (HER4)
      demonstrate improved patient survival. HER4 isoforms and estrogen receptor alpha
      (ER-alpha) can form chaperone complexes causing cell-proliferation. We wanted to
      explore if HER4 isoforms and ER-alpha could correlate to poor prognosis in
      bladder cancers. We developed mRNA assays for HER4 isoforms (JM-a, JM-b, CYT1,
      and CYT2) and for ER-alpha. Expression was analyzed in tumors from 85 bladder
      cancer patients and compared to overall survival (median follow-up of 5.1 years).
      ER-alpha was expressed in 38% (n = 32) of tumors but did not correlate to
      survival (p = 0.4698). HER4 was expressed in 42% (n = 36) and in all cases as the
      ER-alpha binding isoform JM-a. The JM-a isoform can be alternatively spliced to
      either a CYT1 isoform (JM-a/CYT1) or a CYT2 isoform (JM-a/CYT2). All HER4
      expressing tumors expressed the JM-a/CYT2 isoform and half of those (18/36)
      expressed both isoforms. JM-a/CYT2 expression correlated to improved survival (p
      = 0.004), but not when ER-alpha was co-expressed (p = 0.897).
      Immunohistochemistry revealed protein expression of HER4 and ER-alpha in tumor
      cells. Growth of RT4 bladder cancer cells, expressing both JM-a/CYT2 and ER-alpha
      was inhibited by the specific ER-alpha inhibitor raloxifene. Likewise, stable
      transfection with JM-a/CYT2 inhibited the growth of T24 bladder cancer cells, but
      only when ER-alpha was inhibited. Our results demonstrate that HER4 JM-a/CYT2
      expressing bladder cancers relate to favorable prognosis when ER-alpha is not co
      expressed. In vitro studies indicate that ER-alpha inhibition may be a useful
      treatment for patients with tumors expressing both ER-alpha and HER4 JM-a/CYT2.

PMID- 24015959
TI  - Chemoenzymatic synthesis of novel C-ribosylated naphthoquinones.
AB  - The biological activity of many natural products is dependent on the presence of
      carbohydrate units, which are usually attached via an O-glycosidic linkage by
      glycosyltransferases. Recently, an exceptional C-ribosylation event was
      discovered in the biosynthesis of the polyketide antibiotic alnumycin A. The two
      step process involves initial attachment of d-ribose-5-phosphate to the
      polyaromatic aglycone by the C-glycosynthase AlnA and subsequent
      dephosphorylation by AlnB, an enzyme of the haloacid dehalogenase family. Here,
      we tested 23 unnatural substrates to probe the C-ribosylation reaction. The
      chemoenzymatic synthesis of C-ribosylated juglone, 7-methyl juglone, monomethyl
      naphthazarin, 8-chloro-7-methyl juglone, and 9-hydroxy-1,4-anthraquinone revealed
      the importance of a 1,4-quinoid system with an adjacent phenolic ring in order
      for reaction to occur. To further rationalize the molecular basis for reactivity,
      factors governing substrate recognition were investigated by NMR binding
      experiments. Additionally, the suitability of substrates for nucleophilic
      substitution was assessed by molecular modeling using density functional theory
      (DFT) calculations. 

PMID- 24015961
TI  - Inhibition of cereal rust fungi by both class I and II defensins derived from the
      flowers of Nicotiana alata.
AB  - Defensins are a large family of small, cysteine-rich, basic proteins, produced by
      most plants and plant tissues. They have a primary function in defence against
      fungal disease, although other functions have been described. This study reports
      the isolation and characterization of a class I secreted defensin (NaD2) from the
      flowers of Nicotiana alata, and compares its antifungal activity with the class
      II defensin (NaD1) from N. alata flowers, which is stored in the vacuole. NaD2,
      like all other class I defensins, lacks the C-terminal pro-peptide (CTPP)
      characteristic of class II defensins. NaD2 is most closely related to Nt-thionin
      from N. tabacum (96% identical) and shares 81% identity with MtDef4 from alfalfa.
      The concentration required to inhibit in vitro fungal growth by 50% (IC50 ) was
      assessed for both NaD1 and NaD2 for the biotrophic basidiomycete fungi Puccinia
      coronata f. sp. avenae (Pca) and P. sorghi (Ps), the necrotrophic pathogenic
      ascomycetes Fusarium oxysporum f. sp. vasinfectum (Fov), F. graminearum (Fgr),
      Verticillium dahliae (Vd) and Thielaviopsis basicola (Tb), and the saprobe
      Aspergillus nidulans. NaD1 was a more potent antifungal molecule than NaD2
      against both the biotrophic and necrotrophic fungal pathogens tested. NaD2 was 5
      10 times less effective at killing necrotrophs, but only two-fold less effective
      on Puccinia species. A new procedure for testing antifungal proteins is described
      in this study which is applicable to pathogens with spores that are not amenable
      to liquid culture, such as rust pathogens. Rusts are the most damaging fungal
      pathogens of many agronomically important crop species (wheat, barley, oats and
      soybean). NaD1 and NaD2 inhibited urediniospore germination, germ tube growth and
      germ tube differentiation (appressoria induction) of both Puccinia species
      tested. NaD1 and NaD2 were fungicidal on Puccinia species and produced stunted
      germ tubes with a granular cytoplasm. When NaD1 and NaD2 were sprayed onto
      susceptible oat plants prior to the plants being inoculated with crown rust, they
      reduced the number of pustules per leaf area, as well as the amount of chlorosis
      induced by infection. Similar to observations in vitro, NaD1 was more effective
      as an antifungal control agent than NaD2. Further investigation revealed that
      both NaD1 and NaD2 permeabilized the plasma membranes of Puccinia spp. This study
      provides evidence that both secreted (NaD2) and nonsecreted (NaD1) defensins may
      be useful for broad-spectrum resistance to pathogens.

PMID- 24015962
TI  - Is in utero exposure to antidepressant drugs really safe?

PMID- 24015960
TI  - Sigma-1 receptor expression in sensory neurons and the effect of painful
      peripheral nerve injury.
AB  - BACKGROUND: The sigma-1 receptor (sigma1R), an endoplasmic reticulum chaperone
      protein, is widely distributed and regulates numerous intracellular processes in
      neurons. Nerve injury alters the structure and function of axotomized dorsal root
      ganglion (DRG) neurons, contributing to the development of pain. The sigma1R is
      enriched in the spinal cord and modulates pain after peripheral nerve injury.
      However, sigma1R expression in the DRG has not been studied. We therefore
      characterized sigma1R expression in DRGs at baseline and following spinal nerve
      ligation (SNL) in rats. RESULTS: Immunohistochemical (IHC) studies in DRG
      sections show sigma1R in both neuronal somata and satellite glial cells. The
      punctate distribution of sigma1R in the neuronal cytoplasm suggests expression in
      the endoplasmic reticulum. When classified by neuronal size, large neurons (>1300
      MUm) showed higher levels of sigma1R staining than other groups (700-1300 MUm,
      <700 MUm). Comparing sigma1R expression in neuronal groups characterized by
      expression of calcitonin gene-related peptide (CGRP), isolectin-B4 (IB4) and
      neurofilament-200 (NF-200), we found sigma1R expression in all three neuronal
      subpopulations, with highest levels of sigma1R expression in the NF-200 group.
      After SNL, lysates from L5 DRGs that contains axotomized neurons showed decreased
      sigma1R protein but unaffected transcript level, compared with Control DRGs. IHC
      images also showed decreased sigma1R protein expression, in SNL L5 DRGs, and to a
      lesser extent in the neighboring SNL L4 DRGs. Neurons labeled by CGRP and NF-200
      showed decreased sigma1R expression in L5 and, to a lesser extent, L4 DRGs. In
      IB4-labeled neurons, sigma1R expression decreased only in axotomized L5 DRGs.
      Satellite cells also showed decreased sigma1R expression in L5 DRGs after SNL.
      CONCLUSIONS: Our data show that sigma1R is present in both sensory neurons and
      satellite cells in rat DRGs. Expression of sigma1R is down-regulated in
      axotomized neurons as well as in their accompanying satellite glial cells, while
      neighboring uninjured neurons show a lesser down-regulation. Therefore, elevated
      sigma1R expression in neuropathic pain is not an explanation for pain relief
      after sigma1R blockade. This implies that increased levels of endogenous sigma1R
      agonists may play a role, and diminished neuroprotection from loss of glial
      sigma1R may be a contributing factor.

PMID- 24015963
TI  - A new catheter for pulmonary vein isolation: the hole story?

PMID- 24015964
TI  - Herbert Asa Perkins, MD.

PMID- 24015965
TI  - Adolescent pedometer protocols: examining reactivity, tampering and participants'
      perceptions.
AB  - The aim of this study was to investigate adolescents' potential reactivity and
      tampering while wearing pedometers by comparing different monitoring protocols to
      accelerometer output. The sample included adolescents (N = 123, age range = 14-15
      years) from three secondary schools in New South Wales, Australia. Schools were
      randomised to one of the three pedometer monitoring protocols: (i) daily sealed
      (DS) pedometer group, (ii) unsealed (US) pedometer group or (iii) weekly sealed
      (WS) pedometer group. Participants wore pedometers (Yamax Digi-Walker CW700,
      Yamax Corporation, Kumamoto City, Japan) and accelerometers (Actigraph GT3X+,
      Pensacola, USA) simultaneously for seven days. Repeated measures analysis of
      variance was used to examine potential reactivity. Bivariate correlations between
      step counts and accelerometer output were calculated to explore potential
      tampering. The correlation between accelerometer output and pedometer steps/day
      was strongest among participants in the WS group (r = 0.82, P <= 0.001), compared
      to the US (r = 0.63, P <= 0.001) and DS (r = 0.16, P = 0.324) groups. The DS (P
      <= 0.001) and US (P = 0.003), but not the WS (P = 0.891), groups showed evidence
      of reactivity. The results suggest that reactivity and tampering does occur in
      adolescents and contrary to existing research, pedometer monitoring protocols may
      influence participant behaviour.

PMID- 24015966
TI  - Palliative treatment of skin metastases in dermato-oncology.
AB  - Patients with metastatic melanoma, but also other solid tumors (e.g., lung or
      breast cancer), may develop cutaneous metastases in advanced stages. The goal of
      treatment is to alleviate symptoms such as pain, fetor, secretions, or bleeding.
      Current treatment modalities are based on a multimodal treatment approach. Beside
      surgery, treatment options such as electrochemotherapy, isolated limb perfusion,
      radiotherapy, and local administration of cytokines or chemotherapy agents are
      available. In case of concomitant visceral metastases, this local treatment
      approach may not affect overall survival, but the palliation of these tumor
      associated symptoms very often improves the quality of life for the patient. 

PMID- 24015967
TI  - Discovery of epigenetic regulator I-BET762: lead optimization to afford a
      clinical candidate inhibitor of the BET bromodomains.
AB  - The bromo and extra C-terminal domain (BET) family of bromodomains are involved
      in binding epigenetic marks on histone proteins, more specifically acetylated
      lysine residues. This paper describes the discovery and structure-activity
      relationships (SAR) of potent benzodiazepine inhibitors that disrupt the function
      of the BET family of bromodomains (BRD2, BRD3, and BRD4). This work has yielded a
      potent, selective compound I-BET762 that is now under evaluation in a phase I/II
      clinical trial for nuclear protein in testis (NUT) midline carcinoma and other
      cancers. 

PMID- 24015968
TI  - Cognitively challenging physical activity benefits executive function in
      overweight children.
AB  - This study tested the association between aerobic fitness and executive function
      and the impact of enhanced, cognitively challenging physical activity on
      executive function in overweight and lean children. Seventy children aged 9-10
      years were assigned to either a 6-month enhanced physical education programme
      including cognitively demanding (open skill) activities or curricular physical
      education only. Pre- and post-intervention tests assessed aerobic capacity (Leger
      test) and two components of executive function: inhibition and working memory
      updating (random number generation task). Indices of inhibition and memory
      updating were compared in higher- and lower-fit children and intervention effects
      were evaluated as a function of physical activity programme (enhanced vs.
      curricular) and weight status (lean vs. overweight). Results showed better
      inhibition in higher- than lower-fit children, extending the existing evidence of
      the association between aerobic fitness and executive function to new aspects of
      children's inhibitory ability. Overweight children had more pronounced pre- to
      post-intervention improvements in inhibition than lean children only if involved
      in enhanced physical education. Such intervention effects were not mediated by
      aerobic fitness gains. Therefore, the cognitive and social interaction challenges
      inherent in open skill tasks, even though embedded in a low-dose physical
      activity programme, may represent an effective means to promote cognitive
      efficiency, especially in overweight children.

PMID- 24015969
TI  - Intracluster correlation coefficients and reliability of randomized multicenter
      stroke trials within VISTA.
AB  - BACKGROUND: Reliable estimates of intracluster correlation coefficients (ICCs)
      for specific outcome measures are crucial for sample size calculations of future
      cluster randomized trials. ICCs indicate the proportion of data variability that
      is explained by defined levels of clustering. AIMS: In this manuscript, we
      present potentially valuable and reliable estimates of ICCs for specific baseline
      and follow-up data. METHOD: ICCs were estimated from linear and generalized
      linear mixed models using maximum likelihood estimation for common measures used
      in stroke research, including modified Rankin Scale (mRS), National Institutes of
      Health Stroke Scale (NIHSS), and Barthel Index (BI). RESULTS: Data were available
      for 11 841 patients with ischemic stroke from 11 randomized trials. After
      adjusting for age, thrombolysis, and baseline NIHSS, the median ICC for follow-up
      data, using center as the level of clustering, ranged from 0.007 to 0.041. The
      ICCs using trial, continent or year of enrollment as level of clustering were
      distinctly lower. Less than 1% of the variability of mRS, NIHSS, and BI was
      explained by any of these three cluster levels. CONCLUSION: This compendium of
      relevant ICC estimates should assist trial planning. For example, the sample size
      for a cluster trial with 150 patients per center using ordinal analysis of mRS
      should be inflated by 2.0 due to the ICC of 0.007; whereas the ICC of 0.031 using
      mRS dichotomized above mRS 0-1, requires inflation by 5.6. The low contribution
      of trials, year or continent of enrollment to overall variation in outcome offers
      reassurance that analyses using pooled data from multiple trials in VISTA are
      unlikely to suffer from bias from these sources.

PMID- 24015970
TI  - Elucidation of the mechanism of reaction between S2O8(2-), Selenite and Mn2+ in
      aqueous solution and limestone-gypsum FGD liquor.
AB  - The mechanism of reaction between peroxodisulfate ion (S2O8(2-)), selenite
      (Se(IV)O3(2-)) and Mn(2+) as an inhibitor of selenite oxidation was studied using
      aqueous solutions composed of commercial reagents, as well as limestone-gypsum
      flue gas desulfurization (FGD) liquors sampled from coal fired power plants. The
      oxidation of selenite to selenate (Se(VI)O4(2-)) is promoted by the sulfate ion
      radical (SO4(-)) which results from decomposition of S2O8(2-). In the presence of
      Mn(2+), selenite oxidation was prevented due to the difference in rates of
      reaction with SO4(-). The ratio of the oxidation rate constants of selenite and
      Mn(2+) with SO4(-) was determined over a temperature range of 40-60  degrees C,
      and was found to be little influenced by the various coexisting components in FGD
      liquors. 

PMID- 24015971
TI  - Aromatic oligoamide macrocycles with a backbone of reduced constraint.
AB  - Oligoamide macrocycles with a backbone partially constrained by hydrogen bonds
      have been prepared. These macrocycles, carrying multiple H-bonding side chains,
      underwent strong aggregation in solution and form long fibers in the solid state.
      In contrast to the strong and specific complexation of the guanidinium ion by
      analogous macrocycles with fully H-bond-constrained backbones, these macrocycles
      failed to recognize the same cation, indicating that reducing backbone constraint
      has led to a drastic change in their cavity. 

PMID- 24015972
TI  - Tetrabenzo[8]circulene: aromatic saddles from negatively curved graphene.
AB  - An aromatic saddle was designed from the hypothetical three-dimensional graphene
      with the negative Gaussian curvature (Schwarzite P192). Two aromatic saddles,
      tetrabenzo[8]circulene (TB8C) and its octamethyl derivative OM-TB8C, were
      synthesized by the Scholl reaction of cyclic octaphenylene precursors. The
      structure of TB8C greatly deviates from planarity, and the deep saddle shape was
      confirmed by single-crystal X-ray crystallography. There are two conformers with
      the S4 symmetry, which are twisted compared to the DFT structure (D2d). The
      theoretical studies propose that the interconversion of TB8C via the planar
      transition state (125 kcal mol(-1)) is not possible. However, the pseudorotation
      leads to a low-energy tub-to-tub inversion via the nonplanar transition state
      (7.3 kcal mol(-1)). The ground-state structure of TB8C in solution is quite
      different from the X-ray structure because of the crystal-packing force and low
      energy pseudorotation. OM-TB8C is a good electron donor and works as the p-type
      semiconductor. 

PMID- 24015973
TI  - Regulated provider perceptions of feedback reports.
AB  - AIM: This paper reports on regulated (or licensed) care providers' understanding
      and perceptions of feedback reports in a sample of Canadian long-term care
      settings using a cross-sectional survey design. BACKGROUND: Audit with feedback
      quality improvement studies have seldom targeted front-line providers in long
      term care to receive feedback information. METHODS: Feedback reports were
      delivered to front-line regulated care providers in four long-term care
      facilities for 13 months in 2009-10. Providers completed a postfeedback survey.
      RESULTS: Most (78%) regulated care providers (n = 126) understood the reports and
      felt they provided useful information for making changes to resident care (64%).
      Perceptions of the report differed, depending on the role of the regulated care
      provider. In multivariable logistic regression, the regulated nurses'
      understanding of more than half the report was negatively associated with
      'usefulness of information for changing resident care', and perceiving the report
      as generally useful had a positive association. CONCLUSIONS: Front-line regulated
      providers are an appropriate target for feedback reports in long-term care.
      IMPLICATIONS FOR NURSING MANAGEMENT: Long-term care administrators should share
      unit-level information on care quality with unit-level managers and other
      professional front-line direct care providers.

PMID- 24015974
TI  - Cochlear implants--science, serendipity, and success.

PMID- 24015975
TI  - Titanium-zirconium narrow-diameter versus titanium regular-diameter implants for
      anterior and premolar single crowns: 1-year results of a randomized controlled
      clinical study.
AB  - AIM: To test whether titanium-zirconium (TiZr) 3.3 mm diameter implants perform
      differently from titanium (Ti) 4.1 mm diameter implants with respect to marginal
      bone level (MBL) and clinical parameters. MATERIAL AND METHODS: Forty subjects in
      need of a single implant-supported crown in the anterior or premolar regions were
      recruited in two centres. After random allocation, either a Ti or a TiZr implant
      was placed. Definitive crowns were inserted 6 months after implant placement.
      Implant survival, change in MBL, clinical parameters and occurrence of adverse
      events were assessed at the 1-year examination. RESULTS: At 1 year, 38 of the 40
      included patients were examined (18 Ti and 20 TiZr implants). All the implants
      were in place and stable. From the implant placement to the 1-year examination,
      the change of MBL amounted to -0.40 mm in the Ti group and -0.41 mm in the TiZr
      group. There were no significant differences between the groups regarding the
      change in MBL, the clinical parameters and the occurrence of adverse events.
      CONCLUSIONS: The use of TiZr implants with narrow diameter for the support of
      single crowns in the anterior and premolar regions leads to successful tissue
      integration and clinical performance over a 1-year period.

PMID- 24015976
TI  - Poly(4-styrenesulfonate) as an inhibitor of Abeta40 amyloid fibril formation.
AB  - The formation of amyloid, a cross-beta-sheet fibrillar aggregate of proteins, is
      associated with a variety of neurodegenerative diseases. Amyloidogenic proteins
      such as beta-amyloid (Abeta) are known to exist with a large amount of
      polyelectrolyte macromolecules in vivo. The exact nature of Abeta-polyelectrolyte
      interactions and their roles in Abeta-aggregation are largely unknown. In this
      regard, we report the inhibiting effect of an anionic polyelectrolyte poly(4
      styrenesulfonate) (PSS) on the aggregation of Abeta40 peptide. The results
      demonstrate the strong inhibition potential of PSS on the aggregation of Abeta40
      and imply the dominant role of hydrophobicity of the polyelectrolyte in reducing
      the propensity of Abeta40 amyloid formation. Additional studies with poly(vinyl
      sulfate) (PVS) and p-toluenesulfonate (PTS), which share similar charge density
      with PSS except the former lacking the nonpolar aromatic side chain and the
      latter the aliphatic hydrocarbon backbone, reveal that the presence of both
      aliphatic backbone and aromatic side chain group in PSS is essential for its
      Abeta-aggregation inhibition activity. The interactions involved in the Abeta40
      PSS complex were further investigated using molecular dynamics (MD) simulation.
      Our results provide new insights into the structural interplay between
      polyelectrolytes and Abeta peptide, facilitating the ultimate understanding of
      amyloid formation in Alzheimer's disease. The results should assist in developing
      novel polyelectrolytes as potential chemical tools to study amyloid aggregation. 

PMID- 24015977
TI  - Xyloglucan-cellulose nanocrystal multilayered films: effect of film architecture
      on enzymatic hydrolysis.
AB  - Understanding the hydrolysis process of lignocellulosic substrates remains a
      challenge in the biotechnology field. We aimed here at investigating the effect
      of substrate architecture on the enzymatic degradation process using two
      different multilayered model films composed of cellulose nanocrystals (CNCs) and
      xyloglucan (XG) chains. They were built by a spin-assisted layer-by-layer (LbL)
      approach and consisted either of (i) an alternation of CNC and XG layers or of
      (ii) layers of mixed (CNC/XG) complexes alternated with polycation layers.
      Neutron reflectivity (NR) was used to determine the architecture and composition
      of these films and to characterize their swelling in aqueous solution. The films
      displayed different [XG]/[CNC] ratios and swelling behavior. Enzymatic
      degradation of films was then performed and investigated by quartz crystal
      microbalance with dissipation monitoring (QCM-D). We demonstrated that some
      architectural features of the substrate, such as polysaccharide accessibility,
      porosity, and cross-links, influenced the enzymatic degradation. 

PMID- 24015978
TI  - Dental amalgam and urinary mercury concentrations: a descriptive study.
AB  - BACKGROUND: Dental amalgam is a source of elemental and inorganic mercury. The
      safety of dental amalgam in individuals remains a controversial issue. Urinary
      mercury concentrations are used to assess chronic exposure to elemental mercury.
      At present, there are no indications of mercury-associated adverse effects at
      levels below 5 MUg Hg/g creatinine (Cr) or 7 MUg Hg/L (urine). The purpose of the
      present study is to determine the overall urinary mercury level in the Canadian
      general population in relation to the number of dental amalgam surfaces. METHODS:
      Data come from the 2007/09 Canadian Health Measures Survey, which measured
      urinary mercury concentrations in a nationally representative sample of 5,418
      Canadians aged 6-79 years. Urinary mercury concentrations were stratified by sex,
      age, and number of dental amalgam surfaces. RESULTS: The overall mean urinary
      mercury concentration varied between 0.12 MUg Hg/L and 0.31 MUg Hg/L or 0.13 MUg
      Hg/g Cr and 0.40 MUg Hg/g Cr. In general, females showed slightly higher mean
      urinary mercury levels than men. The overall 95th percentile was 2.95 MUg Hg/L,
      the 99th percentile was 7.34E MUg Hg/L, and the 99.9th percentile was 17.45 MUg
      Hg/L. Expressed as MUg Hg/g Cr, the overall 95th percentile was 2.57 MUg Hg/g Cr,
      the 99th percentile was 5.65 MUg Hg/g Cr, and the 99.9th percentiles was 12.14
      MUg Hg/g Cr. Overall, 98.2% of participants had urinary mercury levels below 7
      MUg Hg/L and 97.7% had urinary mercury levels below 5 MUg Hg/g Cr. All data are
      estimates for the Canadian population. The estimates followed by the letter "E"
      should be interpreted with caution due to high sampling variability (coefficient
      of variation 16.6%-33.3%). CONCLUSIONS: The mean urinary mercury concentrations
      in the general Canadian population are significantly lower than the values
      considered to pose any risks for health.

PMID- 24015979
TI  - Is pregnancy a trigger for recovery from an eating disorder?
AB  - OBJECTIVE: Pregnancy produces significant changes in a woman's body weight and
      shape. This study examines changes in body mass index (BMI) and quality of life
      related to eating disorders (QOLED) prior to, during and after pregnancy in both
      women with and without eating disorders. DESIGN: Prospective study. SETTING:
      Royal North Shore Hospital, Northshore Private and Northside Clinic, Sydney.
      SAMPLE: The study comprised 178 pregnant women. METHODS: Women completed the
      QOLED questionnaire retrospectively before pregnancy, prospectively for each
      trimester of pregnancy and at 3, 6 and 12 months postpartum. The QOLED is a
      validated questionnaire used to assess quality of life related to eating
      disorders, including physical health, social function and psychological state.
      Changes in current BMI and QOLED were examined across the stages of pregnancy.
      RESULTS: The women with eating disorders (n = 19) had significantly lower BMIs
      before, during and after pregnancy. Both women with and without eating disorders
      had significant weight gain in the second and third trimesters compared with pre
      pregnancy. There were significant interactions between stage of pregnancy and
      eating disorder status on global QOLED scores. These scores improved
      significantly during second and third trimesters compared with pre-pregnancy but
      varied after pregnancy, particularly among women with eating disorders. The QOLED
      scores for women with eating disorders remained within the eating disorder range
      throughout the study. CONCLUSIONS: Pregnancy is not associated with recovery from
      eating disorders. Women with eating disorders need support during pregnancy and
      the postnatal year, and should not be told that their eating disorder will
      improve during this time.

PMID- 24015980
TI  - Early changes in myocardial repolarization and coronary perfusion after
      cardiopulmonary bypass surgery for ASD repair in children.
AB  - BACKGROUND: In adults, impaired myocardial repolarization and increased risk of
      arrhythmia are known consequences of open heart surgery. Little is known,
      however, about post-operative consequences of cardiopulmonary bypass surgery in
      children. The aim of this study was to assess ventricular repolarization and
      coronary perfusion after bypass surgery for atrial septal defect (ASD) repair in
      children. METHODS: Twelve patients with ASD were assessed one day before and 5-6
      days after ASD repair. Myocardial repolarization (corrected QT interval, QTc, QT
      dispersion, QTd, and PQ interval) was determined on 12-lead electrocardiograms.
      Coronary flow in proximal left anterior descending artery (peak flow velocity in
      diastole, PFVd) was assessed by transthoracic Doppler echocardiography. RESULTS:
      Ten of the 12 (83%) children had normal myocardial repolarization before and
      after surgery. After surgery, QTc increased 1-9% in 5 (42%) patients, decreased 2
      11% in 5 (42%) patients and did not change in 2 (16%) patients. Post-op QTc
      positively correlated with bypass time (R=0.686, p=0.014) and changes in PFVd
      (R=0.741, p=0.006). After surgery, QTd increased 33-67% in 4 (33%) patients,
      decreased 25-50% in 6 patients (50%) and did not change in 2 (16%) patients.
      After surgery, PQ interval increased 5-30% in 4 (33%) patients, decreased 4-29%
      in 6 (50%) patients and did not change in 1 (8%) patient. Post-op PQ positively
      correlated with bypass time (R=0.636, p=0.027). As previously reported, PFVd
      significantly increased after surgery (p<0.001). CONCLUSIONS: Changes in QTc, PQ
      and PFVd are common in young children undergoing surgery for ASD repair. Post-op
      QTc significantly correlates with bypass time, suggesting prolonged
      cardiopulmonary bypass may impair ventricular repolarization. Post-op QTc
      significantly correlates with PFVd changes, suggesting increased coronary flow
      may also impair ventricular repolarization. The clinical significance and
      reversibility of these alternations require further investigations.

PMID- 24015981
TI  - A psychometric analysis and standardization of the Behavior Assessment System for
      Children-2, Self-Report of Personality, Child Version among a Korean sample.
AB  - The psychometric properties of the Korean version of the Behavior Assessment
      System for Children-2, Self-Report of Personality, Child Form (K-BASC-2 SRP-C)
      are reported. A total of 1100 Korean children ages 8-11 years participated in the
      study to establish normative data. The results of this study generally supported
      the factor structure and reliability of the various clinical, adaptive, and
      composite scale scores of the K-BASC-2 SRP-C. A separate sample of 738 Korean
      children was used to examine the convergent validity of a subset of the K-BASC-2
      SRP-C scales related to anxiety, depression, and attention problems. Results
      revealed generally strong psychometric properties of the K-BASC-2 SRP-C. The one
      exception was the Self-Esteem scale: its reliability is low.

PMID- 24015982
TI  - Effects of peer victimization on psychological and academic adjustment in early
      adolescence.
AB  - The purpose of the current study is to investigate the effects of frequency of
      peer victimization experiences on psychological and academic adjustment during
      early adolescence, with a focus on testing psychological adjustment as a
      mediator, as well as differences based on gender and type of victimization. The
      sample in this short-term longitudinal design study consists of 7th and 8th
      graders (n = 670, 50% male) from an ethnically and socioeconomically diverse
      middle school. Victimization was measured using 10 items that assessed frequency
      of verbal, physical, and relational victimization experiences, and outcomes were
      assessed with the Behavior Assessment System for Children (2nd ed.) and school
      records. There was support for gender differences in frequency of peer
      victimization experiences based on type of victimization. More specifically, boys
      reported higher levels of physical and verbal victimization, and girls reported
      higher levels of relational victimization. In addition, there were statistically
      significant differences between boys and girls on the relation between
      victimization and anxiety, attendance, and grades, with girls experiencing more
      maladjustment than boys in response to peer victimization. Finally, results
      demonstrated no gender differences in indirect effects of psychological
      adjustment on the relation between peer victimization and academic outcomes,
      whether victimization was physical, verbal, and relational. These findings
      highlight the importance of addressing social-emotional functioning as well as
      peer victimization in the schools for both boys and girls, as both affect
      students' academic functioning.

PMID- 24015983
TI  - Improving classroom learning environments by Cultivating Awareness and Resilience
      in Education (CARE): results of a randomized controlled trial.
AB  - Cultivating Awareness and Resilience in Education (CARE for Teachers) is a
      mindfulness-based professional development program designed to reduce stress and
      improve teachers' performance and classroom learning environments. A randomized
      controlled trial examined program efficacy and acceptability among a sample of 50
      teachers randomly assigned to CARE or waitlist control condition. Participants
      completed a battery of self-report measures at pre- and postintervention to
      assess the impact of the CARE program on general well-being, efficacy,
      burnout/time pressure, and mindfulness. Participants in the CARE group completed
      an evaluation of the program after completing the intervention. ANCOVAs were
      computed between the CARE group and control group for each outcome, and the
      pretest scores served as a covariate. Participation in the CARE program resulted
      in significant improvements in teacher well-being, efficacy, burnout/time-related
      stress, and mindfulness compared with controls. Evaluation data showed that
      teachers viewed CARE as a feasible, acceptable, and effective method for reducing
      stress and improving performance. Results suggest that the CARE program has
      promise to support teachers working in challenging settings and consequently
      improve classroom environments.

PMID- 24015984
TI  - Increasing self-regulatory energy using an Internet-based training application
      delivered by smartphone technology.
AB  - Self-control resources can be defined in terms of "energy." Repeated attempts to
      override desires and impulses can result in a state of reduced self-control
      energy termed "ego depletion" leading to a reduced capacity to regulate future
      self-control behaviors effectively. Regular practice or "training" on self
      control tasks may improve an individual's capacity to overcome ego depletion
      effectively. The current research tested the effectiveness of training using a
      novel Internet-based smartphone application to improve self-control and reduce
      ego depletion. In two experiments, participants were randomly assigned to either
      an experimental group, which received a daily program of self-control training
      using a modified Stroop-task Internet-based application delivered via smartphone
      to participants over a 4-week period, or a no-training control group.
      Participants assigned to the experimental group performed significantly better on
      post-training laboratory self-control tasks relative to participants in the
      control group. Findings support the hypothesized training effect on self-control
      and highlight the effectiveness of a novel Internet-based application delivered
      by smartphone as a practical means to administer and monitor a self-control
      training program. The smartphone training application has considerable advantages
      over other means to train self-control adopted in previous studies in that it has
      increased ecological validity and enables effective monitoring of compliance with
      the training program.

PMID- 24015985
TI  - Cyberbullying behavior and adolescents' use of media with antisocial content: a
      cyclic process model.
AB  - The present study examined the role of media use in adolescents' cyberbullying
      behavior. Following previous research, we propose a Cyclic Process Model of face
      to-face victimization and cyberbullying through two mediating processes of
      anger/frustration and antisocial media content. This model was tested utilizing a
      cross-sectional design with adolescent participants (N=892). Exposure to
      antisocial media content was measured with a newly developed content-based scale
      (i.e., the C-ME), showing good psychometric qualities. Results of structural
      equation modeling showed that adolescents' exposure to antisocial media content
      was significantly associated with cyberbullying behavior, especially in
      adolescents who experienced anger and frustration due to face-to-face
      victimization. Goodness of fit indices demonstrated a good fit of the theoretical
      model to the data and indicated that exposure to antisocial media content acts as
      an amplifier in a cyclic process of victimization-related anger and cyberbullying
      behavior.

PMID- 24015986
TI  - Structure-guided discovery of a novel aminoglycoside conjugate targeting HIV-1
      RNA viral genome.
AB  - The dimerization initiation site (DIS) of the HIV-1 genomic RNA is a conserved
      stem-loop that promotes viral genome dimerization by forming a loop-loop complex.
      The DIS constitutes a potentially interesting target because it is crucial for
      several key steps of the viral replication. In this work we describe the
      synthesis of a rationally designed aminoglycoside conjugate that binds the HIV-1
      DIS viral RNA with high specificity, as shown by an extensive in vitro binding
      characterization. We propose a three-dimensional model of the drug-RNA
      interaction that perfectly fits with binding data. Our results show the
      feasibility of targeting the HIV DIS viral RNA dimer and open the way to the
      rationale design of a new class of antiviral drugs. In addition, due to
      similarities between the HIV-1 DIS RNA and the bacterial aminoacyl decoding site
      (A site) RNA, we show that this novel aminoglycoside conjugate also binds the
      bacterial A site with a similar affinity as natural aminoglycoside antibiotics. 

PMID- 24015987
TI  - Protein phosphatase 2A as a potential target for treatment of adult T cell
      leukemia.
AB  - The aim of this study was to establish the role of serine/threonine protein
      phosphatase 2A (PP2A) in the survival of leukemic cells from patients with adult
      T cell leukemia (ATL), associated with human T cell leukemia virus type 1 (HTLV
      1). In HTLV-1-infected T cell lines and ATL cells, okadaic acid (OkA), a potent
      PP2A inhibitor, induced decrease in cell viability and G1 cell cycle arrest by
      decreasing the expression levels of cyclin D2, cyclin-dependent kinase 4 and
      cyclin-dependent kinase 6, phosphorylation of pRb, and upregulation of p21, p27
      and GADD45alpha. OkA-induced apoptosis was also due to the suppression of
      expression of Bcl-2, Bcl-x(L) and XIAP, and the activation of caspases-3, -8 and 
      9, and caspase-3 downstream mammalian STE20-like kinase 1 and H2AX. OkA inhibited
      nuclear factor-kappa B DNA binding and activated mitogen-activated protein (MAP)
      kinases. Other new PP2A-specific inhibitors, cytostatin and rubratoxin A, also
      induced decrease in cell viability through caspase-dependent mechanism. MAP
      kinase inhibitors confirmed the role of p38 MAP kinase in PP2A inhibitors-induced
      apoptosis. OkA resulted in the generation of reactive oxygen species, and
      exogenous antioxidant prevented activation of the indicated caspases. Finally,
      PP2A knockdown inhibited cell growth. The results showed that PP2A inhibition
      caused reactive oxygen species generation and affected distinct signaling
      pathways, resulting in the activation of H2AX and subsequent apoptotic cell
      death. These results suggest that PP2A is a potentially useful target in the
      treatment of ATL.

PMID- 24015988
TI  - Significance of prion and prion-like proteins in cancer development, progression
      and multi-drug resistance.
AB  - Prions are renowned for their role in neurodegenerative diseases in humans and
      animals. These are manifested as transmissible spongiform encephalopathies (TSEs)
      that result from the conversion of the normal glycosylphosphatidylinositol (GPI)
      anchored cellular prion protein (PrP(c)) to a misfolded, aggregated and
      pathogenic form, prion protein scrapie (PrP(Sc)) via a post-translational process
      followed by the accumulation of PrP(Sc) within the central nervous system. New
      research in this area has demonstrated that PrP is over-expressed in a variety of
      cancers including gastric, pancreatic and breast cancers, affecting the growth
      and invasiveness of these cancers as well as playing an important role in the
      acquisition of multi-drug resistant (MDR) gastric cancer. Prion-like doppel
      protein (Dpl), sharing 25% amino acid sequence homology to PrP and whose function
      remains elusive, has also been shown to exhibit a high level of expression in a
      number of cancers including acute myeloid leukemia's, myelodysplastic syndromes,
      gastric adenocarcinoma, anaplastic meningioma and astrocytomas. Furthermore, the
      tumour suppressor protein, p53, already known for its involvement in cancer
      development, has recently been shown to display prion-like tendencies. This
      review provides an overview of prions and prion-like proteins in mammals
      discussing their structure, function and role in cell function and disease.
      Furthermore, current research progress on the role of prion/prion-like proteins
      in the development, progression, and drug resistance of various cancers will be
      summarized. Potential implications for future development of new therapeutic
      treatments targeting prion and prion-like proteins will be discussed. 

PMID- 24015989
TI  - Chaperones of the endoplasmic reticulum are required for Ve1-mediated resistance
      to Verticillium.
AB  - The tomato receptor-like protein (RLP) Ve1 mediates resistance to the vascular
      fungal pathogen Verticillium dahliae. To identify the proteins required for Ve1
      function, we transiently expressed and immunopurified functional Ve1-enhanced
      green fluorescent protein (eGFP) from Nicotiana benthamiana leaves, followed by
      mass spectrometry. This resulted in the identification of peptides originating
      from the endoplasmic reticulum (ER)-resident chaperones HSP70 binding proteins
      (BiPs) and a lectin-type calreticulin (CRT). Knock-down of the different BiPs and
      CRTs in tomato resulted in compromised Ve1-mediated resistance to V. dahliae in
      most cases, showing that these chaperones play an important role in Ve1
      functionality. Recently, it has been shown that one particular CRT is required
      for the biogenesis of the RLP-type Cladosporium fulvum resistance protein Cf-4 of
      tomato, as silencing of CRT3a resulted in a reduced pool of complex glycosylated
      Cf-4 protein. In contrast, knock-down of the various CRTs in N. benthamiana or N.
      tabacum did not result in reduced accumulation of mature complex glycosylated Ve1
      protein. Together, this study shows that the BiP and CRT ER chaperones
      differentially contribute to Cf-4- and Ve1-mediated immunity.

PMID- 24015991
TI  - More bad news for cardiac resynchronization therapy in atrial fibrillation
      patients: what to do?

PMID- 24015990
TI  - The effect of intravenous iron on postoperative transfusion requirements in hip
      fracture patients: study protocol for a randomized controlled trial.
AB  - BACKGROUND: Anaemia following hip fracture is common. Approximately 30 to 45% of
      patients have haemoglobin concentrations below population norms on admission, and
      around 10% are severely anaemic. Anaemia on admission, and in the postoperative
      period, is associated with poor outcomes with regard to mobility, postoperative
      mortality and readmission. There is currently no clear consensus on the optimal
      method of managing perioperative anaemia in this group of frail patients with
      frequent comorbidity. Liberal red cell transfusion in the postoperative period
      does not appear to improve outcome, whereas tranexamic acid appears to reduce
      transfusion rate at the expense of increased cardiovascular morbidity. There are
      encouraging results from one centre with the use of agents to stimulate red cell
      production, including intravenous iron and erythropoietin. UK practice differs
      significantly from these patients and these studies, and it is not clear whether
      these promising results will translate to the UK population. METHODS/DESIGN: This
      is a single-centre randomized controlled parallel group trial, in a British
      university hospital.Randomization is achieved using a website and computer
      generated concealed tables. Participants are 80 patients 70 years or over with
      acute hip fracture undergoing operative repair. The intervention group receive
      three daily infusions of 200 mg iron sucrose, starting within 24 hours of
      admission. The control group receive standard hospital care at the discretion of
      the clinical team. Red cell transfusions for each group are given in accordance
      with standard clinical triggers. The primary outcome is an increase in mean
      reticulocyte count in the intervention group at day 7. Secondary outcome measures
      include haemoglobin concentrations, early and late transfusion rates, infectious
      and cardiovascular complications, mobility and 30-day mortality. DISCUSSION: This
      is a pilot study to demonstrate haematopoietic efficacy of intravenous iron in
      this setting. Hence, we have chosen to measure change in reticulocyte count
      rather than the more clinically relevant differences in haemoglobin concentration
      or transfusion rate. If our results are positive, the study will provide the
      necessary information for development of a full-scale trial of intravenous iron.
      TRIAL REGISTRATION: Current Controlled Trials ISRCTN76424792; UK Medicines and
      Healthcare products Regulatory Authority (EuDRACT: 2011-003233-34).

PMID- 24015992
TI  - Behind the scenes: how visual memory load biases selective attention during
      processing of visual streams.
AB  - We recorded ERPs to investigate whether the visual memory load can bias visual
      selective attention. Participants memorized one or four letters and then
      responded to memory-matching letters presented in a relevant color while ignoring
      distractor letters or letters in an irrelevant color. Stimuli in the relevant
      color elicited larger frontal selection positivities (FSP) and occipital
      selection negativities (OSN) compared to irrelevant color stimuli. Only
      distractors elicited a larger FSP in the high than in the low memory load task.
      Memory load prolonged the OSN for all letters. Response mapping complexity was
      also modulated but did not affect the FSP and OSN. Together, the FSP data suggest
      that high memory load increased distractability. The OSN data suggest that memory
      load sustained attention to letters in a relevant color until working memory
      processing was completed, independently of whether the letters were in working
      memory or not. 

PMID- 24015993
TI  - Surgical correction of common atrium without noncardiac congenital anomalies.
AB  - AIMS: Common atrium (CA) is a rare congenital heart defect. We reviewed our
      experience of surgical treatment of CA and summarize the clinical features of CA
      and the key techniques for surgical correction. METHODS: Between August 1984 and
      August 2010, 37 consecutive cases of CA underwent corrective surgery. There were
      no clinical findings of Down, asplenia-polysplenia or Ellis-van Creveld syndromes
      in all cases. Mitral valvuloplasty was performed in 34 cases, and tricuspid
      valvuloplasty in 20 cases. Complete closure of a mitral cleft was required in 32
      cases. All new atrial septa were reconstructed using patches. Follow-up period
      ranged from 1 to 20 years. RESULTS: There were no hospital deaths or conduction
      system block. After surgery, mild mitral insufficiency was observed in only one
      case. Two cases had moderate-severe mitral insufficiency at postoperative years 1
      and 3, respectively, that required mitral valve replacements. One patient died of
      low cardiac output syndrome after reoperation. CONCLUSIONS: Long-term survival
      after surgical correction of CA is good. Routine closure of a cleft in the mitral
      valve is very important for successful surgery.

PMID- 24015994
TI  - Management of peripheral pulmonary emboli with the use of transvenous catheter
      directed thrombolysis and right ventricular assist device.
AB  - OBJECTIVES: Pulmonary emboli (PE) can result in significant hemodynamic
      instability that requires urgent intervention; however, the management of
      peripheral emboli has been controversial. PATIENTS AND METHODS: We present two
      patients in whom a right ventricular assist device (RVAD) was used in treating
      peripheral pulmonary embolism, applying the technique of pulmonary artery
      catheter-directed thrombolysis after resuscitation with an RVAD. RESULTS: The
      clot burden was not suitable for surgical embolectomy due to its peripheral
      locations. The patients' hemodynamic conditions improved with thrombolytic
      therapy and gradually were weaned off the RVAD. Follow-up scans showed near
      resolution of all PE. CONCLUSION: Catheter-directed thrombolysis with an RVAD as
      an adjunct should be considered in management of peripheral PE.

PMID- 24015999
TI  - A model linking sources of stress to approach and avoidance coping styles of
      Turkish basketball referees.
AB  - Purpose of this study was to externally validate and test a conceptual transient
      model involving six paths that linked sources of acute stress to avoidance and
      approach coping styles among Turkish basketball referees. The sample consisted of
      125 Turkish basketball referees ranging in age from 18 to 36 years (mean = 25.58.
      sigma = 3.69). The path analysis tested the relationships simultaneously from
      stressors, in consecutive order, distractions, subpar performance and verbal
      abuse, to coping styles, first both avoidance-cognitive and approach-cognitive,
      and then approach-behaviour. Results indicated that the model achieved a good fit
      and that all paths tested simultaneously were significant. The distractions
      stressor was positively related to subpar performance, which, in turn, was
      positively related to verbal abuse. Verbal abuse was negatively associated with
      an avoidance-cognitive coping style and positively related to the approach
      cognitive coping style. The results also supported a crossover effect of both
      avoidance-cognitive and approach-cognitive on approach-behaviour. One implication
      of this study is that coping should be studied in naturally occurring stages, a
      process-oriented approach. Another implication is that approach and avoidance
      coping styles, each sub-divided into cognitive and behavioural categories,
      provide a meaningful framework which provides sports officials a coherent
      structure for learning and improving ways to cope with acute stress experienced
      during the contest.

PMID- 24016000
TI  - Vemurafenib therapy for stage IV melanoma with V600G-mutation.

PMID- 24016001
TI  - Effects of an acute bout of exercise on serum soluble leptin receptor (sOB-R)
      levels.
AB  - We investigated the effects of an acute bout of exercise on serum soluble leptin
      receptor (sOB-R) concentrations. Eighteen male participants completed two
      different exercise sessions with intensities of 25% and 65% maximal aerobic
      capacity (VO2max). In addition to the energy expenditure during exercise sessions
      being measured, blood samples were collected before exercise, and immediately, at
      24 h, and at 48 h post-exercise to analyse sOB-R, leptin and insulin levels. At
      24 h post-exercise, sOB-R and leptin concentrations at the 65% VO2max were
      significantly different from those at the 25% VO2max. Leptin levels at 48 h post
      exercise were also significantly lower for the 65% VO2max than for the 25% VO2max
      (P < 0.01). In the 65% VO2max session, the energy expenditure during exercise was
      significantly associated with leptin concentrations at 24 h and 48 h and sOB-R
      concentrations at 24 h post-exercise. However, no correlations were found between
      sOB-R and leptin at the three post-exercise time points. In conclusion, an acute
      bout of exercise with 920 kcal of output resulted in an increase in sOB-R levels
      at 24 h post-exercise. However, the changes in sOB-R levels due to an acute bout
      of exercise might not contribute to the delayed decrease observed for leptin.

PMID- 24016003
TI  - Automated microdialysis-based system for in situ microsampling and investigation
      of lead bioavailability in terrestrial environments under physiologically based
      extraction conditions.
AB  - In situ automatic microdialysis sampling under batch-flow conditions is herein
      proposed for the first time for expedient assessment of the kinetics of lead
      bioaccessibility/bioavailability in contaminated and agricultural soils
      exploiting the harmonized physiologically based extraction test (UBM).
      Capitalized upon a concentric microdialysis probe immersed in synthetic gut
      fluids, the miniaturized flow system is harnessed for continuous monitoring of
      lead transfer across the permselective microdialysis membrane to mimic the
      diffusive transport of metal species through the epithelium of the stomach and of
      the small intestine. Besides, the addition of the UBM gastrointestinal fluid
      surrogates at a specified time frame is fully mechanized. Distinct microdialysis
      probe configurations and membranes types were investigated in detail to ensure
      passive sampling under steady-state dialytic conditions for lead. Using a 3-cm
      long polysulfone membrane with averaged molecular weight cutoff of 30 kDa in a
      concentric probe and a perfusate flow rate of 2.0 MUL min(-1), microdialysis
      relative recoveries in the gastric phase were close to 100%, thereby omitting the
      need for probe calibration. The automatic leaching method was validated in terms
      of bias in the analysis of four soils with different physicochemical properties
      and containing a wide range of lead content (16 +/- 3 to 1216 +/- 42 mg kg(-1))
      using mass balance assessment as a quality control tool. No significant
      differences between the mass balance and the total lead concentration in the
      suite of analyzed soils were encountered (alpha = 0.05). Our finding that the
      extraction of soil-borne lead for merely one hour in the GI phase suffices for
      assessment of the bioavailable fraction as a result of the fast immobilization of
      lead species at near-neutral conditions would assist in providing risk assessment
      data from the UBM test on a short notice. 

PMID- 24016002
TI  - Synthesis of a 2-aryl-3-aroyl indole salt (OXi8007) resembling combretastatin A-4
      with application as a vascular disrupting agent.
AB  - The natural products colchicine and combretastatin A-4 are potent inhibitors of
      tubulin assembly, and they have inspired the design and synthesis of a large
      number of small-molecule, potential anticancer agents. The indole-based molecular
      scaffold is prominent among these SAR modifications, leading to a rapidly
      increasing number of agents. The water-soluble phosphate prodrug 33 (OXi8007) of
      2-aryl-3-aroylindole-based phenol 8 (OXi8006) was prepared by chemical synthesis
      and found to be strongly cytotoxic against selected human cancer cell lines (GI50
      = 36 nM against DU-145 cells, for example). The free phenol, 8 (OXi8006), was a
      strong inhibitor (IC50 = 1.1 MUM) of tubulin assembly. The corresponding
      phosphate prodrug 33 (OXi8007) also demonstrated pronounced interference with
      tumor vasculature in a preliminary in vivo study utilizing a SCID mouse model
      bearing an orthotopic PC-3 (prostate) tumor as imaged by color Doppler
      ultrasound. The combination of these results provides evidence that the indole
      based phosphate prodrug 33 (OXi8007) functions as a vascular disrupting agent
      that may prove useful for the treatment of cancer.

PMID- 24016004
TI  - Stable "trait" variance of temperament as a predictor of the temporal course of
      depression and social phobia.
AB  - A large body of research has found robust associations between dimensions of
      temperament (e.g., neuroticism, extraversion) and the mood and anxiety disorders.
      However, mood-state distortion (i.e., the tendency for current mood state to bias
      ratings of temperament) likely confounds these associations, rendering their
      interpretation and validity unclear. This issue is of particular relevance to
      clinical populations who experience elevated levels of general distress. The
      current study used the "trait-state-occasion" latent variable model (D. A. Cole,
      N. C. Martin, & J. H. Steiger, 2005) to separate the stable components of
      temperament from transient, situational influences such as current mood state. We
      examined the predictive power of the time-invariant components of temperament on
      the course of depression and social phobia in a large, treatment-seeking sample
      with mood and/or anxiety disorders (N = 826). Participants were assessed 3 times
      over the course of 1 year, using interview and self-report measures; most
      participants received treatment during this time. Results indicated that both
      neuroticism/behavioral inhibition (N/BI) and behavioral activation/positive
      affect (BA/P) consisted largely of stable, time-invariant variance (57% to 78% of
      total variance). Furthermore, the time-invariant components of N/BI and BA/P were
      uniquely and incrementally predictive of change in depression and social phobia,
      adjusting for initial symptom levels. These results suggest that the removal of
      state variance bolsters the effect of temperament on psychopathology among
      clinically distressed individuals. Implications for temperament-psychopathology
      models, psychopathology assessment, and the stability of traits are discussed.

PMID- 24016005
TI  - Impaired retrieval of semantic information in bipolar disorder: a clustering
      analysis of category-fluency productions.
AB  - On category-cued verbal fluency tasks, such as animal naming, respondents often
      report exemplars in semantically related clusters. We (Sung et al., 2012) used
      this tendency to elucidate sources of semantic dysfunction in adults with
      schizophrenia (SZ). Many patients with bipolar disorder (BD) show cognitive
      deficits that are similar to but milder than those seen in SZ. Whether this
      similarity extends to the functioning of the semantic system is unclear. To test
      the hypothesis that it does, we adapted a clustering technique called singular
      value decomposition (SVD) to investigate the clustering pattern of semantic
      retrieval in BD. Two category-fluency tasks (animal and supermarket-item naming)
      were administered to 98 adult outpatients with BD and 98 healthy adults (NC) who
      matched the BD group in age, sex, education, and estimated premorbid IQ. Results
      of clustering analysis showed that patients with BD produced less coherent
      category clusters than healthy adults. Specifically, patients with BD showed less
      coherent clusters of low-frequency animal names, but their overall productivity
      was not more impaired than the NCs'. In the supermarket condition, patients not
      only showed incoherent clustering of named supermarket items regardless of their
      frequencies, but also produced smaller numbers of exemplars than NCs did. The
      semantic system abnormalities shown by adults with BD were similar to those we
      found previously in persons with SZ, although the group differences were smaller.
      Overall, these results point to a concept retrieval/access deficit in BD and
      underscore the importance of analyzing the content of category-fluency
      productions.

PMID- 24016006
TI  - Psychophysiologic reactivity, subjective distress, and their associations with
      PTSD diagnosis.
AB  - Intense subjective distress and physiologic reactivity upon exposure to reminders
      of the traumatic event are each diagnostic features of posttraumatic stress
      disorder (PTSD). However, subjective reports and psychophysiological data often
      suggest different conclusions. For the present study, we combined data from five
      previous studies to assess the contributions of these two types of measures in
      predicting PTSD diagnosis. One hundred fifty trauma-exposed participants who were
      classified into PTSD or non-PTSD groups based on structured diagnostic interviews
      completed the same script-driven imagery procedure, which quantified measures of
      psychophysiologic reactivity and self-reported emotional responses. We derived
      four discriminant functions (DiscFxs) that each maximally separated the PTSD from
      the non-PTSD group using (1) psychophysiologic measures recorded during personal
      mental imagery of the traumatic event; (2) self-report ratings in response to the
      trauma imagery; (3) psychophysiologic measures recorded during personal mental
      imagery of another highly stressful experience unrelated to the index traumatic
      event; and (4) self-report ratings in response to this other stressor. When PTSD
      status was simultaneously regressed on all four DiscFxs, trauma-related
      psychophysiological reactivity was a significant predictor, but physiological
      reactivity resulting from the highly stressful, but not traumatic script, was
      not. Self-reported distress to the traumatic experience and the other stressful
      event were both predictive of PTSD diagnosis. Trauma-related psychophysiologic
      reactivity was the best predictor of PTSD diagnosis, but self-reported distress
      contributed additional variance. These results are discussed in relation to the
      Research Domain Criteria framework.

PMID- 24016007
TI  - Posttraumatic cognitions and posttraumatic stress symptoms among war-affected
      children: a cross-lagged analysis.
AB  - In a longitudinal study of war-affected children, we tested, first, whether
      posttraumatic cognitions (PTCs) mediated the relationship between initial and
      later posttraumatic stress symptoms (PTSSs). Second, we analyzed the relative
      strength of influences that PTCs and PTSSs have on each other in cross-lagged
      models of levels and latent change scores. The participants were 240 Palestinian
      children 10-12 years of age, reporting PTSSs and PTCs measures at 3, 5, and 11
      months after a major war. Results show that PTCs did not mediate between initial
      and later PTSSs. The levels and changes in PTCs statistically significantly
      predicted later levels and changes in PTSSs, but PTSSs did not statistically
      significantly predict later PTCs. The results are consistent with the hypothesis
      that PTCs have a central role in the development and maintenance of PTSSs over
      time, but they do not support the hypothesis that initial PTSSs develop to
      chronic PTSSs through negative PTCs.

PMID- 24016008
TI  - Biomarkers of threat and reward sensitivity demonstrate unique associations with
      risk for psychopathology.
AB  - Two emotional/motivational constructs that have been posited to underlie anxiety
      and depressive disorders are heightened sensitivity to threat and reduced
      sensitivity to reward, respectively. It is unclear, though, whether these
      constructs are only epiphenomena or also connote risk for these disorders (and
      relatedly, whether they connote risk for separate disorders). Using family
      history of psychopathology as an indicator of risk, the present study examined
      whether biomarkers of sensitivity to threat (startle potentiation) and reward
      (frontal EEG asymmetry) were associated with similar or different familial
      liabilities. In addition, the present study examined whether these biomarkers
      were associated with risk independent of proband DSM-IV diagnosis. One-hundred
      and seventy-three individuals diagnosed with panic disorder (PD), early onset
      major depressive disorder (MDD), both (comorbids), or controls completed two
      laboratory paradigms assessing sensitivity to predictable/unpredictable threat
      (measured via startle response) and reward (measured via frontal EEG asymmetry
      during a gambling task). Results indicated that across all participants: (a)
      startle potentiation to unpredictable threat was associated with family history
      of PD (but not MDD); and (b) frontal EEG asymmetry while anticipating reward was
      associated with family history of MDD (but not PD). Additionally, both measures
      continued to be associated with family history of psychopathology after
      controlling for proband DSM-IV diagnosis. Results suggest that the proposed
      biomarkers of sensitivity to unpredictable threat and reward exhibit discriminant
      validity and may add to the predictive validity of the DSM-IV defined constructs
      of PD and MDD, respectively.

PMID- 24016009
TI  - Natural course of preadolescent loss of control eating.
AB  - Cross-sectional evidence shows that loss of control (LOC) eating is a common and
      psychopathologically relevant experience in preadolescence. This study sought to
      investigate the natural course of preadolescent LOC eating in relation to
      psychopathology and body weight trajectory. A community sample of 55 children
      ages 8-13 years with LOC eating, defined as at least one episode of LOC eating
      within the past 3 months (LOC+), and 59 matched children without LOC history (LOC
      ), were assessed with the Eating Disorder Examination adapted for Children and
      self-report questionnaires every 6 months over a 2-year follow-up. Of the LOC+
      children, 54.5% of children remitted from LOC eating, 3.6% showed persistent LOC
      eating, and 41.8% showed recurring LOC eating over the follow-up period. Of the
      LOC- children, 19% revealed an onset of LOC episodes, mostly with a low level of
      stability. Multilevel modeling showed that LOC eating predicted a partial binge
      eating disorder diagnosis and greater global eating disorder psychopathology, but
      not depressive symptoms or growth in body fatness. Between-person higher shape
      concern and weight-related teasing, as well as within-person decreases in shape
      concern and increases in depression, predicted a greater likelihood of subsequent
      LOC eating. The results indicate a moderate stability of LOC eating in
      preadolescent children, with prognostic significance for clinically relevant
      eating problems and eating disorder psychopathology.

PMID- 24016010
TI  - The relation of weight suppression and body mass index to symptomatology and
      treatment response in anorexia nervosa.
AB  - Weight suppression, the difference between highest past weight and current
      weight, is a robust predictor of clinical characteristics of bulimia nervosa;
      however, the influence of weight suppression in anorexia nervosa (AN) has been
      little studied, and to our knowledge, no study to date has investigated the ways
      in which the relevance of weight suppression in AN may depend upon an
      individual's current body mass index (BMI). The present study investigated weight
      suppression, BMI, and their interaction as cross-sectional and prospective
      predictors of psychological symptoms and weight in AN. Women with AN completed
      depression (Beck Depression Inventory-II) and eating disorder symptomatology
      measures (Eating Disorder Examination Questionnaire and Eating Disorders
      Inventory-3) at residential treatment admission (N = 350) and discharge (N =
      238). Weight suppression and BMI were weakly correlated (r = -.22). At admission,
      BMI was positively correlated with all symptom measures except Restraint and
      Depression scores. Weight suppression was also independently positively
      correlated with all measures except Weight Concern and Body Dissatisfaction
      subscale scores. In analyses examining discharge scores (including admission
      values as covariates), the admission weight suppression * BMI interaction
      consistently predicted posttreatment psychopathology. Controlling for weight gain
      in treatment and age, higher admission weight suppression predicted lower
      discharge scores (less symptom endorsement) among those with lower BMIs; among
      those with higher BMIs, higher weight suppression predicted higher discharge
      scores. These results are the first to our knowledge to demonstrate that absolute
      and relative weight status are joint indicators of AN severity and prognosis.
      These findings may have major implications for conceptualization and treatment of
      AN.

PMID- 24016012
TI  - DSM-IV-TR and DSM-5 eating disorders in adolescents: prevalence, stability, and
      psychosocial correlates in a population-based sample of male and female
      adolescents.
AB  - The current study aimed to compare the prevalence, stability, and psychosocial
      correlates of DSM-IV-TR and DSM-5 eating disorders, in a population-based sample
      of male and female adolescents followed prospectively from 14 to 20 years of age.
      Participants (N = 1,383; 49% male) were drawn from the Western Australian
      Pregnancy Cohort (Raine) Study, a prospective, population-based cohort study that
      has followed participants from prebirth to young adulthood. Detailed self-report
      questionnaires were used to assess eating disorder symptoms when participants
      were aged 14, 17, and 20 years. Comparisons between DSM-IV-TR and DSM-5 were
      conducted using McNemar chi-square tests and Fisher's exact tests. Changes in
      eating disorder prevalence over time were considered using generalized estimating
      equations. Eating disorder prevalence rates were significantly greater when using
      DSM-5 than DSM-IV-TR criteria, at all time points for females and at age 17 only
      for males. "Unspecified"/"other" eating disorder diagnoses were significantly
      less common when applying DSM-5 than DSM-IV-TR criteria, but still formed 15% to
      30% of the DSM-5 cases. Diagnostic stability was low for all disorders, and DSM-5
      binge eating disorder or purging disorder in early adolescence predicted DSM-5
      bulimia nervosa in later adolescence. Cross-over from binge eating disorder to
      bulimia nervosa was particularly high. Regardless of the diagnostic
      classification system used, all eating disorder diagnoses were associated with
      depressive symptoms and poor mental health quality of life. These results provide
      further support for the clinical utility of DSM-5 eating disorder criteria, and
      for the significance of binge eating disorder and purging disorder.

PMID- 24016011
TI  - The role of affect in the maintenance of anorexia nervosa: evidence from a
      naturalistic assessment of momentary behaviors and emotion.
AB  - The current study examines the relationship of affect and eating disorder
      behavior in anorexia nervosa (AN) using ecological momentary assessment.
      Participants were 118 adult females recruited at three sites from eating disorder
      treatment centers and community advertisements. All participants met full
      Diagnostic and statistical manual of mental disorders (4th ed.) criteria or
      subthreshold criteria for AN. Participants were provided handheld computers and
      asked to report positive affect, negative affect, loss of control (LOC) eating,
      purging, exercise, drinking fluids to curb appetite, and weighing one's self
      multiple times per day as well as dietary restriction once daily over a 2-week
      interval. Mixed-effects models were used to examine the extent to which affective
      states predict dietary restriction. In addition, we used two analytic approaches
      to compare affect before and after other eating disorder behaviors. We found that
      higher daily ratings of negative affect were associated with a greater likelihood
      of dietary restriction on subsequent days. When examining the single rating
      immediately before and after behaviors, we found that negative affect increased
      significantly after LOC eating, purging, the combination of LOC and
      eating/purging, and weighing of one's self. Using this same analytic approach, we
      also found negative affect to decrease significantly after the consumption of
      fluids to curb appetite and exercise. When examining the covariation of AN
      behaviors and negative affect assessed multiple times in the hours and minutes
      before the behaviors, we found negative affect significantly increased before LOC
      eating, purging, the combination of LOC eating/and purging, and weighing
      behavior. Negative affect also significantly decreased after the occurrence of
      these behaviors. These findings are consistent with the idea that that negative
      affect is potentially a critical maintenance mechanism of some AN symptoms, but
      that the analytic approach used to examine affect and behavior may have
      significant implications on the interpretation of findings.

PMID- 24016013
TI  - Examination of affective and cognitive interference in schizophrenia and relation
      to symptoms.
AB  - The nature of emotion deficits in schizophrenia and anhedonia is still unclear,
      and understanding the nature of these deficits could help improve treatment of
      chronic symptoms and functional disability. An important mechanism in emotional
      functioning is attention to affective information. People with schizophrenia (n =
      48) and a nonpsychiatric comparison group (n = 28) completed an affective
      interference task, a task used to assess attention to affective information.
      Given that the affective interference task also involves prepotent response
      inhibition, participants also completed a very similar, but nonaffective,
      cognitive interference task that involves prepotent inhibition but does not
      require attention to affective information. Results revealed that people with
      schizophrenia exhibited decreased affective interference on trials with a shorter
      length of time between the onset of the cue and onset of the target but increased
      cognitive interference at all time lengths between the cue and target onsets used
      in the study. In addition, decreased affective interference was associated with
      increased anhedonia and increased reports of wanting to ignore positive emotions.
      In contrast, increased cognitive interference was associated with increased
      communication disturbances and alogia. Overall, these results suggest that there
      may be a decrease in attention to affective information in schizophrenia and that
      affective interference is related to anhedonia. At the same time, these results
      provide further evidence of cognitive control prepotent inhibition deficits in
      schizophrenia, which are related to communication disturbances and alogia.

PMID- 24016014
TI  - Alcohol stress response dampening during imminent versus distal, uncertain
      threat.
AB  - Research indicates that fear and anxiety are distinct processes with separable
      neurobiological substrates. Predictable versus unpredictable shock administration
      has been used to elicit fear versus anxiety, respectively. Recent research has
      demonstrated that alcohol may reduce anxiety but not fear. However, previous
      manipulations of predictability have varied both probability and temporal
      uncertainty of shock threat, leaving unresolved questions regarding which
      stimulus characteristics elicit anxiety and are sensitive to alcohol stress
      response dampening (SRD). We developed a novel paradigm to closely parallel basic
      research in animals that systematically varied temporal uncertainty of threat
      while holding threat probability constant. Intoxicated (0.08% target blood
      alcohol concentration), placebo, and no-alcohol control participants viewed a
      series of visual threat cues. Certain cue duration (5 s) blocks were equivalent
      to predictable shock blocks eliciting fear in earlier research. Uncertain cue
      duration (5, 20, 50, or 80 s, intermixed) blocks introduced temporal uncertainty
      regarding impending shock to elicit anxiety. Startle potentiation relative to
      matched cue periods in no-shock blocks provided the primary measure of affective
      response. All threat cues produced robust startle potentiation. Alcohol reduced
      startle potentiation during the first 5 s of threat cue presentation in uncertain
      but not certain duration blocks. Alcohol also reduced startle potentiation at
      later times among longer uncertain duration cues, suggesting that alcohol SRD
      persisted. Trait negative emotionality and binge drinking status moderated
      alcohol SRD magnitude during uncertain threat. These translational findings
      corroborate previous reports regarding distinct substrates of fear versus anxiety
      and have implications for both alcoholism etiology and comorbidity with anxiety
      disorders.

PMID- 24016015
TI  - The effect of alcohol on emotional inertia: a test of alcohol myopia.
AB  - Alcohol myopia (AM) has emerged as one of the most widely researched theories of
      alcohol's effects on emotional experience. Given this theory's popularity, it is
      notable that a central tenet of AM has not been tested-namely, that alcohol
      creates a myopic focus on the present moment, limiting the extent to which the
      present is permeated by emotions derived from prior experience. We tested the
      impact of alcohol on moment-to-moment fluctuations in affect, applying advances
      in emotion assessment and statistical analysis to test this aspect of AM without
      drawing the attention of participants to their own emotional experiences. We
      measured emotional fluctuations using autocorrelation, a statistic borrowed from
      time-series analysis measuring the correlation between successive observations in
      time. High emotion autocorrelation is termed emotional inertia and is linked to
      negative mood outcomes. Social drinkers (N = 720) consumed alcohol, placebo, or
      control beverages in groups of 3 over a 36-min group formation task. We indexed
      affect using the Duchenne smile, recorded continuously during the interaction
      (34.9 million video frames) according to the Facial Action Coding System (P.
      Ekman, W. V. Friesen, & J. C. Hager, 2002). Autocorrelation of Duchenne smiling
      emerged as the most consistent predictor of self-reported mood and social bonding
      when compared with Duchenne smiling mean, standard deviation, and linear trend.
      Alcohol reduced affective autocorrelation, and autocorrelation mediated the link
      between alcohol and self-reported mood and social outcomes. Findings suggest that
      alcohol enhances the ability to freely enjoy the present moment untethered by
      past experience and highlight the importance of emotion dynamics in research
      examining affective correlates of psychopathology.

PMID- 24016016
TI  - Pubertal development, personality, and substance use: a 10-year longitudinal
      study from childhood to adolescence.
AB  - Most research linking early pubertal development to substance use has focused on
      the effects of pubertal timing (age at which a certain stage of pubertal
      development is reached or pubertal status at a particular age--related to the
      maturation disparity hypothesis), but little research has focused on pubertal
      tempo (rate of growth through pubertal stages--related to the maturation
      compression hypothesis). However, both timing and tempo have not only been
      identified as important components of pubertal development, with different
      predictors, but have also been shown to be independently associated with other
      adolescent psychopathologies. Using latent growth-curve modeling, this study
      examined how pubertal status at age 12 and pubertal tempo (between 11 and 13
      years) related to substance use from 15 to 16 years in boys from low
      socioeconomic backgrounds (N = 871). Results showed that both pubertal status at
      age 12 and tempo were significant predictors of increased levels of substance use
      and problems in mid to late adolescence. In an attempt to identify mechanisms
      that may explain the association between pubertal development and substance use
      it was found that sensation seeking partially mediated the association between
      pubertal status at age 12 and substance use behaviors. Impulse control was found
      to moderate the association sensation seeking had with marijuana use frequency,
      with high sensation-seeking scores predicting higher marijuana use frequency only
      at low levels of impulse control. These findings highlight the importance of
      considering multiple sources of individual variability in the pubertal
      development of boys and provide support for both the maturational disparity and
      compression hypotheses.

PMID- 24016018
TI  - Prediction of psychopathology and functional impairment by positive and negative
      schizotypy in the Chapmans' ten-year longitudinal study.
AB  - The present study examined the predictive validity of psychometrically assessed
      positive and negative schizotypy in the Chapmans' 10-year longitudinal data set.
      Schizotypy provides a useful construct for understanding the etiology and
      development of schizophrenia and related disorders. Schizotypy and schizophrenia
      share a common multidimensional structure that includes positive and negative
      symptom dimensions. Recent cross-sectional studies have supported the validity of
      psychometric positive and negative schizotypy; however, the present study is the
      first to examine the predictive validity of these dimensions. The Chapmans'
      longitudinal data provided an ideal opportunity because of the large sample size,
      high reassessment rate, and extended interval between assessments. A total of 534
      psychometric high-risk and control participants were initially assessed, and 95%
      of this sample was reinterviewed 10 years later. As hypothesized, positive and
      negative schizotypy uniquely predicted the development of schizophrenia-spectrum
      disorders. At the reassessment, both positive and negative schizotypy predicted
      psychotic-like, schizotypal, and paranoid symptoms, as well as poorer adjustment.
      The positive dimension was associated with mood and substance use disorders and
      mental health treatment. Negative schizotypy was associated with schizoid
      symptoms and social impairment at the follow-up. The results extend the growing
      validity findings for psychometrically assessed positive and negative schizotypy
      by demonstrating that they are associated with the development of differential
      patterns of symptoms and impairment.

PMID- 24016017
TI  - Feature-based attention and conflict monitoring in criminal offenders:
      interactive relations of psychopathy with anxiety and externalizing.
AB  - As predicted by the response modulation model, psychopathic offenders are
      insensitive to potentially important inhibitory information when it is peripheral
      to their primary focus of attention. To date, the clearest tests of this
      hypothesis have manipulated spatial attention to cue the location of goal
      relevant versus inhibitory information. However, the theory predicts a more
      general abnormality in selective attention. In the current study, male prisoners
      performed a conflict-monitoring task, which included a feature-based manipulation
      (i.e., color) that biased selective attention toward goal-relevant stimuli and
      away from inhibitory distracters on some trials but not others. Paralleling
      results for spatial cuing, feature-based cuing resulted in less distracter
      interference, particularly for participants with primary psychopathy (i.e., low
      anxiety). This study also investigated the moderating effect of externalizing on
      psychopathy. Participants high in psychopathy but low in externalizing performed
      similarly to primary psychopathic individuals. These results demonstrate that the
      abnormal selective attention associated with primary psychopathy is not limited
      to spatial attention but, instead, applies to diverse methods for establishing
      attentional focus. Furthermore, they demonstrate a novel method of investigating
      psychopathic subtypes using continuous analyses.

PMID- 24016019
TI  - Interrelations between psychosocial functioning and adaptive- and maladaptive
      range personality traits.
AB  - Decrements in one or more domains of psychosocial functioning (e.g., poor job
      performance, poor interpersonal relations) are commonly observed in psychiatric
      patients. The purpose of this study is to increase understanding of psychosocial
      functioning as a broad, multifaceted construct as well as its associations with
      both adaptive- and maladaptive-range personality traits in both nonclinical and
      psychiatric outpatient samples. The study was conducted in two phases. In Study
      1, a nonclinical sample (N = 429) was administered seven psychosocial functioning
      and adaptive-range personality trait measures. In Study 2, psychiatric
      outpatients (N = 181) were administered the same psychosocial functioning
      measures, and maladaptive- as well as adaptive-range personality trait measures.
      Exploratory (both studies) and confirmatory (Study 2) factor analyses indicated a
      common three-factor, hierarchical structure of psychosocial functioning-Well
      Being, Social/Interpersonal Functioning, and Basic Functioning. These
      psychosocial functioning domains were closely--and differentially--linked with
      personality traits, especially strongly so in patients. Across samples, Well
      Being was associated with both Neuroticism/Negative Affectivity and
      Extraversion/Positive Affectivity, Social/Interpersonal Functioning was
      associated with both Agreeableness and Conscientiousness/Disinhibition, and Basic
      Functioning was associated with Conscientiousness/Disinhibition, although only
      modestly in the nonclinical sample. These relations generally were maintained
      even after partialing out current general dysphoric symptoms. These findings have
      implications for considering psychosocial functioning as an important third
      domain in a tripartite model together with personality and psychopathology.

PMID- 24016020
TI  - The hierarchical structure of clinician ratings of proposed DSM-5 pathological
      personality traits.
AB  - Preliminary explorations of the trait model for personality disorders provided in
      Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) Section
      III suggest that the factor structure of proposed traits includes 5 higher order
      factors that resemble other dimensional trait models of personality. These prior
      investigations have been based on self-reported data obtained from personality
      questionnaires, as has much of the research literature from which such trait
      models have evolved. However, the DSM-5 itself involves judgments made by
      clinicians about their patients. Thus, it is important to examine whether this
      factor structure identified in recent studies can also be found in clinician
      rating data. This study examined the hierarchical structure of the 25 proposed
      DSM-5 traits in patient ratings provided by a sample of 337 mental health
      professionals. Exploratory factor analysis revealed a hierarchical structure that
      resembled previously reported trait structures. As with a prior investigation by
      Wright et al. (2012), the various solutions estimated in the hierarchy of the DSM
      5 traits resembled existing models of common mental disorders, temperament, and
      personality pathology.

PMID- 24016021
TI  - The association of ADHD and depression: mediation by peer problems and parent
      child difficulties in two complementary samples.
AB  - Children with attention-deficit/hyperactivity disorder (ADHD) are at increased
      risk for the development of depression, with evidence that peer and academic
      difficulties mediate predictions of later depression from ADHD. In the present
      study, we hypothesized that parent-child relationship difficulties may be an
      additional potential mediator of this association. Academic, peer, and parent
      child functioning were tested as mediators of the association of attention
      problems and depression in two distinctly different yet complementary samples.
      Study 1 was a cross-sectional sample of 5- to 10-year-old children (N = 230) with
      and without ADHD. Study 2 was a prospective longitudinal sample of 472 youth,
      followed prospectively from birth to age 20 years, at risk for depression.
      Despite differences in age, measures, and designs, both studies implicated peer
      and parent-child problems as unique mediators of depressive symptoms, whereas
      academic difficulties did not uniquely mediate the ADHD-depression association.
      Furthermore, inattention symptoms, but not hyperactivity, predicted depressive
      symptoms via the disruption of interpersonal functioning. The inclusion of
      oppositional defiant disorder into models impacted results and supported its
      independent role in parent-child problems. Implications include support for
      interventions that target interpersonal competence, which may effectively reduce
      the risk of depression among children with ADHD.

PMID- 24016022
TI  - Effects of subtype of attention-deficit/hyperactivity disorder in adults on
      lateralized readiness potentials during a go/no-go choice reaction time task.
AB  - We studied 40 young adults with attention-deficit/hyperactivity disorder (ADHD;
      18 predominantly inattentive type, 22 combined type) and 38 demographically
      comparable controls in a go/no-go choice reaction time task with 2 levels of
      difficulty. The ADHD/combined group was less accurate and had more variable
      reactions than controls. The ADHD/inattentive sample was slower than controls and
      had smaller early lateralized readiness potentials (LRPs). Compared with
      controls, both subtypes had (a) smaller early LRPs for no-go stimuli and (b)
      relatively earlier LRP onsets for difficult no-go events. The ADHD/combined
      sample also had smaller late LRP waves than controls. The results suggest that
      adults with ADHD, particularly those with the combined subtype, exhibit weaker
      central preparation to respond to both stimuli requiring a motor response and
      those prompting response inhibition.

PMID- 24016023
TI  - Mapping the country within: a special section on reconceptualizing the
      classification of mental disorders.
AB  - At the outset of the golden era of cartography, fifteenth-century Europeans drew
      the earth as they wished it to be. Some maps were so fanciful as to show four
      continents like petals centered around Jerusalem. It would take a century of
      adventurers, navigators, mathematicians, and artists to align the map with the
      actual places where the rocks met the seas. In this effort, there were many lost
      voyages and sailors. Fictitious islands and isthmuses arose and fell. Yet even in
      their nascent form, the maps suggested important destinations and passages. They
      did not have to be perfect to be useful. Doubtless, there were times in the Age
      of Discovery when navigators were forced to choose between an old and dear map
      that had not been fully discredited, and a new and unknown picture of the world
      that remained yet unproved. How then did they decide which to trust? This special
      section of the Journal of Abnormal Psychology is designed to explore this
      question with three review papers and a commentary all composed by leading
      psychopathologists, the navigators and cartographers of our discipline. In the
      end, the DSM-5 became something more akin to a DSM-IV-TR-revised, as opposed to
      enshrining the new diagnostic paradigm the task force chairs originally sought.
      While there were several innovations, such as a chapter structure that better
      reflected data on the empirical organization of psychopathology, the old map was
      largely retained with a few of the sea monsters relocated.

PMID- 24016025
TI  - Classification and psychopathology research.
AB  - The classification of psychopathology appears to be at a crossroads, with a new
      version of the Diagnostic and Statistical Manual of Mental Disorders impending
      and one of the current aspirations of the National Institute of Mental Health
      being the development of new ways of classifying mental disorders. This article
      discusses what we currently know about psychopathology and the role that
      classification has played in psychopathology research. It is pointed out that a
      wide variety of etiological factors, both within and outside the individual, have
      been implicated in the etiology of psychopathology, and that there is no
      empirical or conceptual reason to privilege any particular level of explanation.
      The ways in which signs/symptoms and disorders may be related are discussed,
      including their implications for classification. The value of theory development
      and theory-driven research is emphasized, along with the potential perils of
      generating an ossified classification scheme that must be adhered to.

PMID- 24016026
TI  - A construct-network approach to bridging diagnostic and physiological domains:
      application to assessment of externalizing psychopathology.
AB  - A crucial challenge in efforts to link psychological disorders to neural systems,
      with the aim of developing biologically informed conceptions of such disorders,
      is the problem of method variance (Campbell & Fiske, 1959). Since even measures
      of the same construct in differing domains correlate only moderately, it is
      unsurprising that large sample studies of diagnostic biomarkers yield only modest
      associations. To address this challenge, a construct-network approach is proposed
      in which psychometric operationalizations of key neurobehavioral constructs serve
      as anchors for identifying neural indicators of psychopathology-relevant
      dispositions, and as vehicles for bridging between domains of clinical problems
      and neurophysiology. An empirical illustration is provided for the construct of
      inhibition-disinhibition, which is of central relevance to problems entailing
      deficient impulse control. Findings demonstrate that: (1) a well-designed
      psychometric index of trait disinhibition effectively predicts externalizing
      problems of multiple types, (2) this psychometric measure of disinhibition shows
      reliable brain response correlates, and (3) psychometric and brain-response
      indicators can be combined to form a joint psychoneurometric factor that predicts
      effectively across clinical and physiological domains. As a methodology for
      bridging between clinical problems and neural systems, the construct-network
      approach provides a concrete means by which existing conceptions of psychological
      disorders can accommodate and be reshaped by neurobiological insights.

PMID- 24016027
TI  - Constructing constructs for psychopathology: the NIMH research domain criteria.
AB  - As a commentary for the special section on Reconceptualizing the Classification
      of Mental Disorders, this article begins with a description of the impetus for
      the U.S. National Institute of Mental Health's (NIMH) Research Domain Criteria
      (RDoC) initiative and provides an update of progress on that initiative to date.
      The commentary then engages the articles in this special section, beginning with
      a response to Berenbaum's concern that the RDoC approach to sorting constructs
      across multiple units of analysis espouses a de facto biological fundamentalism.
      This leads us to delineate the relationship between RDoC and the NIMH priorities
      relevant to this initiative. The commentary then considers how Patrick's
      iterative "construct-network" method can be applied to RDoC construct validation,
      highlighting several aspects that are particularly useful. One aspect of this
      work involves determining subject inclusion and exclusion criteria that provide
      an appropriate range of variance. Finally, this commentary considers the Bilder
      group's article, explicating the ways in which multilevel models can foster
      development of hypotheses and informatics approaches needed for further RDoC
      progress.

PMID- 24016028
TI  - Real-time colorimetric assay of inorganic pyrophosphatase activity based on
      reversibly competitive coordination of Cu2+ between cysteine and pyrophosphate
      ion.
AB  - In this study we demonstrate a new colorimetric method for real-time
      pyrophosphatase (PPase) activity assay based on reversible tuning of the
      dispersion/aggregation states of gold nanoparticles (Au-NPs) by controlling the
      coordination of Cu(2+) between cysteine and pyrophosphate ion (PPi) with PPase.
      The addition of Cu(2+) to the cysteine-stabilized Au-NP dispersion results in the
      aggregation of Au-NPs, while the further addition of PPi to this aggregation
      turns the aggregated Au-NPs into their dispersed state because of the higher
      coordination reactivity between Cu(2+) and PPi than that between Cu(2+) and
      cysteine. The subsequent addition of PPase to the PPi-triggered dispersed Au-NPs
      restores the aggregation state of Au-NPs because PPase catalyzes the hydrolysis
      of PPi into orthophosphate and thus consumes PPi in the reaction system. In this
      study, we utilize this reversibility of the change between the
      aggregation/dispersion states of Au-NPs for real-time colorimetric monitoring of
      PPase activity by continuously measuring the ratio of absorbance at the
      wavelength of 650 nm (A650) to that at 522 nm (A522) in the time-dependent UV-vis
      spectra of Au-NP dispersions containing different activities of PPase. To
      calculate the kinetics of the PPase-catalyzed hydrolysis of PPi, the A650/A522
      values are converted into PPi concentrations to obtain the time-dependent changes
      of PPi concentrations in the dispersions containing different activities of
      PPase. The initial reaction rates (v0) are thus achieved from the time-dependent
      logarithm of PPi concentrations with the presence of different PPase activities.
      Under the experimental conditions employed here, the v0 values are linear with
      the PPase activity within a range from 0.025 to 0.4 U with a detection limit down
      to 0.010 U (S/N = 3). Moreover, the colorimetric method developed here is also
      employed for PPase inhibitor evaluation. This study offers a simple yet effective
      method for real-time PPase activity assay. 

PMID- 24016030
TI  - Sick regimes and sick people: a multilevel investigation of the population health
      consequences of perceived national corruption.
AB  - OBJECTIVE: There is a paucity of empirical work on the potential population
      health impact of living under a regime marred by corruption. African countries
      differ in the extent of national corruption, and we explore whether perceived
      national corruption is associated with population health across all rungs of
      society. METHODS: World Health Survey data were analysed on 72 524 adults from 20
      African countries. The main outcome was self-reported poor general health.
      Multilevel logistic regression was used to assess the association between poor
      health and perceived corruption, while jointly accounting for individual- and
      country-level human development factors. In this research, we use Transparency
      International's corruption perception index (CPI), which measures 'both
      administrative and political corruption' on a 0-10 scale. A higher score pertains
      to a higher rate of perceived corruption within society. We also examined effect
      modification by gender, age and socio-economic status. RESULTS: Higher national
      corruption perception was consistently associated with an increase in poor health
      prevalence, also after multivariable adjustments, with odds ratio (OR) of 1.62
      (95% CI: 1.01-2.60). Stratified analyses by age and gender suggested this same
      pattern in all subgroups. Positive associations between poor health and perceived
      corruption were evident in all socio-economic groups, with the association being
      somewhat more positive among less educated people (OR = 1.61, 95% CI: 1.01-2.58)
      than among more educated people (OR = 1.40, 95% CI: 0.83-2.37). CONCLUSIONS: This
      study is a cautious first step in empirically testing the general health
      consequences of corruption. Our results suggest that higher perceived national
      corruption is associated with general health of both men and women within all
      socio-economic groups across the lifespan. Further research is needed using more
      countries to assess the magnitude of the health consequences of corruption.

PMID- 24016031
TI  - Systematic review of human listeriosis in China, 1964-2010.
AB  - OBJECTIVES: Listeria is an important foodborne pathogen with severe
      manifestations and high case-fatality rate. However, listeriosis is not yet a
      notifiable disease in China, and there is no national monitoring system for
      cases. We conducted a systematic review to better understand the clinical and
      epidemiologic features of listeriosis in China. METHODS: Both electronic and
      manual retrieval systems were used to search Chinese literature for cases and
      isolates of human listeriosis reported between 1964 and 2010. We recorded and
      analysed demographic, clinical and laboratory information available for reported
      cases. RESULTS: A total of 147 clinical cases, 479 Listeria isolates and 82
      outbreak-related cases were reported in 28 (90%) provinces in China from January
      1964 to December 2010. Of the clinical cases, 45 (31%) were central nervous
      system infections, 68 (46%) were septicaemia and 34 (23%) were focal infections
      or gastroenteritis. The overall case-fatality rate was 26% (34/130) among
      clinical cases with known outcomes and 46% (21/46) among neonatal cases.
      CONCLUSION: Listeriosis cases occurred in China throughout the study period
      between 1964 and 2010. Case-fatality was similar to published data from other
      countries. China should consider requiring notification of listeriosis cases to
      improve estimates of incidence, identification of risk factors and design of
      preventive measures.

PMID- 24016032
TI  - Effect of HSV-2 on population-level trends in HIV incidence in Uganda between
      1990 and 2007.
AB  - OBJECTIVE: To assess the long-term effects of population-level HSV-2 infection on
      HIV incidence. METHODS: Data from a population-based cohort in south-western
      Uganda were used to estimate HIV incidence from 1990 to 2007. Stored blood
      samples were tested for HSV-2, and the impact of HSV-2 prevalence and incidence
      on HIV incidence was estimated by calculating population attributable fractions
      (PAFs). The association between population-level annual HIV incidence and annual
      HSV-2 incidence/prevalence was analysed using linear regression. RESULTS: HIV
      incidence declined over time among men, from 8.72/1000 person-years (pyr) in 1990
      to 4.85/1000 pyr in 2007 (P-trend <0.001). In contrast, there was no decline in
      HIV incidence among women (4.86/1000 pyr in 1990 to 6.74/1000 pyr in 2007, P
      trend = 0.18). PAFs of incident HIV attributable to HSV-2 were high (60% in
      males; 70% in females). There was no evidence of an association between long-term
      trends in HIV incidence and HSV-2 prevalence or incidence. CONCLUSION: Assuming a
      causal relationship, a substantial proportion of new HIV infections in this
      population are attributable to HSV-2. The study did not find an effect of HSV-2
      prevalence/incidence on trends in HIV incidence. HIV incidence did not vary much
      during the study period. This may partly explain the lack of association.

PMID- 24016034
TI  - Effect of adenosine A1 receptor agonist on the enhanced excitability of spinal
      dorsal horn neurons after peripheral nerve injury.
AB  - Neuronal hyperactivity has been implicated in abnormal pain sensation following
      peripheral nerve injuries. Previous studies have indicated that the activation of
      adenosine A1 receptors (A1R) in the central and peripheral nervous systems
      produces an antinociceptive effect. However, the mechanisms involved in the
      peripheral effect are still not fully understood. The effects of the local
      application of the selective A1R agonist, 2-chloro-N(6)-cyclopentyladenosine
      (CCPA) on neuronal hyperactivity were examined in this study using a neuropathic
      pain model induced by a tibial nerve injury. We utilized Fos protein-like
      immunoreactivity induced by noxious heat stimulation to examine changes in the
      number of Fos protein like immunoreactive (Fos-LI) neuron profiles in the spinal
      dorsal horn, and behavioral analysis for mechanical and thermal sensitivities.
      The nerve injury induced an exaggerated Fos response to noxious heat stimulation.
      The number of Fos-LI neuron profiles was significantly decreased and their
      distribution was restricted to the central terminal field of the spared peroneal
      nerve 3 days after the injury. The number of Fos-LI neuron profiles returned to
      control levels and a large number of these profiles were observed in the central
      terminal field of the injured tibial nerve 14 days after the injury. These
      enhanced Fos responses were attenuated by the local application of CCPA. The
      nerve injury also resulted in mechanical allodynia and thermal hyperalgesia. The
      local application of CCPA inhibited thermal hyperalgesia, but was less effective
      against mechanical allodynia. These results indicated that activation of
      peripheral A1R plays a role in the regulation of nerve injury-induced
      hyperalgesia. 

PMID- 24016033
TI  - Nasopharyngeal bacterial colonisation in HIV-positive children in Cambodia.
AB  - OBJECTIVE: To determine patterns of nasopharyngeal colonisation in HIV-positive
      children. METHODS: Nasopharyngeal, nasal and ear swabs were prospectively taken
      from all children living in two paediatric nursing homes for HIV-positive orphans
      in Cambodia from 2004 to 2011. RESULTS: A total of 882 swabs were taken, of which
      586 tested positive for bacteria. Staphylococcus aureus was the most frequently
      isolated species (178 isolates; 30.4%) followed by Streptococcus pneumoniae (103
      isolates; 17.6%) and Klebsiella pneumoniae (99 isolates; 16.9%). The rate of S.
      pneumoniae decreased in 2009 when a vaccination programme was introduced.
      CONCLUSIONS: The respiratory tract of HIV-positive children receiving highly
      active antiretroviral therapy is commonly colonised by S. aureus and S.
      pneumoniae, while other species normally found in the respiratory tract, such as
      Moraxella catarrhalis, are far less frequent.

PMID- 24016035
TI  - One phase of the dormancy developmental pathway is critical for the evolution of
      insect seasonality.
AB  - Evolutionary change in the timing of dormancy enables animals and plants to adapt
      to changing seasonal environments and can result in ecological speciation.
      Despite its clear biological importance, the mechanisms underlying the evolution
      of dormancy timing in animals remain poorly understood because of a lack of
      anatomical landmarks to discern which phase of dormancy an individual is
      experiencing. Taking advantage of the nearly universal characteristic of
      metabolic suppression during insect dormancy (diapause), we use patterns of
      respiratory metabolism to document physiological landmarks of dormancy and test
      which of the distinct phases of the dormancy developmental pathway contribute to
      a month-long shift in diapause timing between a pair of incipient moth species.
      Here, we show that divergence in life cycle between the earlier-emerging E-strain
      and the later-emerging Z-strain of European corn borer (ECB) is clearly explained
      by a delay in the timing of the developmental transition from the diapause
      maintenance phase to the termination phase. Along with recent findings indicating
      that life-cycle differences between ECB strains stem from allelic variation at a
      single sex-linked locus, our results demonstrate how dramatic shifts in animal
      seasonality can result from simple developmental and genetic changes. Although
      characterizing the multiple phases of the diapause developmental programme in
      other locally adapted populations and species will undoubtedly yield surprises
      about the nature of animal dormancy, results in the ECB moth suggest that
      focusing on genetic variation in the timing of the dormancy termination phase may
      help explain how (or whether) organisms rapidly respond to global climate change,
      expand their ranges after accidental or managed introductions, undergo seasonal
      adaptation, or evolve into distinct species through allochronic isolation. 

PMID- 24016037
TI  - Quality of life in patients with endometriosis and the effect of pertubation with
      lidocaine - a randomized controlled trial.
AB  - OBJECTIVE: Pertubation with lidocaine has been shown to reduce pain (on a VAS
      scale) in women with endometriosis. A clinical study was performed to evaluate
      the effect of lidocaine pertubations on quality of life. DESIGN: Double-blind,
      randomized and controlled trial. SETTING: Three outpatient units in Stockholm,
      Sweden. POPULATION: Eligible patients had endometriosis with dysmenorrhoic pain
      >VAS 50 mm. METHODS: The patients were randomized to pre-ovulatory pertubations
      with lidocaine (n = 24) or placebo (n = 18) during three consecutive menstrual
      cycles. The procedure comprised passing the solution through the uterus and the
      Fallopian tubes via an intracervical balloon catheter. The effect was evaluated
      with the validated Endometriosis Health Profile-30 questionnaire before and after
      treatments. MAIN OUTCOME MEASURES: Changes in scores at six and 12 months from
      baseline were compared between the groups with the Mann-Whitney U-test. RESULTS:
      After 6 months there was a significant difference between the lidocaine (n = 19)
      and the placebo (n = 16) groups for the dimension social support (median -18.8
      vs. -6.3, p = 0.034), whereas there were no significant differences for the other
      dimensions after 6 or 12 months. The mean changes in the lidocaine group were
      above the minimal important difference levels in eight of 12 measurements of
      quality of life dimensions compared with two of 12 in the placebo group.
      CONCLUSIONS: This clinical trial indicates that pertubations with lidocaine might
      improve the social support dimension of quality of life in patients with
      endometriosis.

PMID- 24016036
TI  - Development of a culture system to induce microglia-like cells from
      haematopoietic cells.
AB  - AIMS: Microglia are the resident immune cells in the central nervous system,
      originating from haematopoietic-derived myeloid cells. A microglial cell is a
      double-edged sword, which has both pro-inflammatory and anti-inflammatory
      functions. Although understanding the role of microglia in pathological
      conditions has become increasingly important, histopathology has been the only
      way to investigate microglia in human diseases. METHODS: To enable the study of
      microglial cells in vitro, we here establish a culture system to induce microglia
      like cells from haematopoietic cells by coculture with astrocytes. The
      characteristics of microglia-like cells were analysed by flow cytometry and
      functional assay. RESULTS: We show that triggering receptor expressing on myeloid
      cells-2-expressing microglia-like cells could be induced from lineage negative
      cells or monocytes by coculture with astrocytes. Microglia-like cells exhibited
      lower expression of CD45 and MHC class II than macrophages, a characteristic
      similar to brain microglia. When introduced into brain slice cultures, these
      microglia-like cells changed their morphology to a ramified shape on the first
      day of the culture. Moreover, we demonstrated that microglia-like cells could be
      induced from human monocytes by coculture with astrocytes. Finally, we showed
      that interleukin 34 was an important factor in the induction of microglia-like
      cells from haematopoietic cells in addition to cell-cell contact with astrocytes.
      Purified microglia-like cells were suitable for further culture and functional
      analyses. CONCLUSION: Development of in vitro induction system for microglia will
      further promote the study of human microglial cells under pathological conditions
      as well as aid in the screening of drugs to target microglial cells.

PMID- 24016038
TI  - Meta-analysis of randomized controlled trials on the efficacy and safety of
      intracoronary administration of tirofiban for no-reflow phenomenon.
AB  - BACKGROUND: Currently, there is still a lack of an optimal treatment for no
      reflow phenomenon (NR). The aim of this simple meta-analysis was to evaluate the
      efficacy and safety of intracoronary (IC) administration of tirofiban compared
      with other conventional drugs during percutaneous coronary intervention (PCI) for
      NR. METHODS: Systematic literature search was done from PubMed, EMBASE, Google
      Scholar, EBSCO, Springer and CNKI databases without language or time limitation.
      Randomized controlled trials were enrolled for analyzing if they investigated the
      treatment of IC administration of tirofiban versus other conventional drugs for
      NR. RESULTS: Ten studies with 702 patients were included. Significantly, the
      treatment of tirofiban was more effective in improving the thrombolysis in
      myocardial infarction (TIMI) flow (OR 0.24, 95% CI 0.15-0.37, P < 0.00001) and
      reducing major adverse cardiovascular events (MACE) (OR 0.09, 95% CI 0.05-0.18, P
      < 0.00001). There was a trend to increase the risk of bleeding, but the data of
      the result did not reach the statistical significance (OR 1.44, 95% CI 0.69-3.00,
      P = 0.32). CONCLUSIONS: Tirofiban is more effective than conventional drugs for
      NR during PCI, but the potential risk of bleeding complication induced by
      tirofiban shouldn't be ignored during clinical practices.

PMID- 24016039
TI  - Maximizing hysteretic losses in magnetic ferrite nanoparticles via model-driven
      synthesis and materials optimization.
AB  - This article develops a set of design guidelines for maximizing heat dissipation
      characteristics of magnetic ferrite MFe2O4 (M = Mn, Fe, Co) nanoparticles in
      alternating magnetic fields. Using magnetic and structural nanoparticle
      characterization, we identify key synthetic parameters in the thermal
      decomposition of organometallic precursors that yield optimized magnetic
      nanoparticles over a wide range of sizes and compositions. The developed
      synthetic procedures allow for gram-scale production of magnetic nanoparticles
      stable in physiological buffer for several months. Our magnetic nanoparticles
      display some of the highest heat dissipation rates, which are in qualitative
      agreement with the trends predicted by a dynamic hysteresis model of coherent
      magnetization reversal in single domain magnetic particles. By combining physical
      simulations with robust scalable synthesis and materials characterization
      techniques, this work provides a pathway to a model-driven design of magnetic
      nanoparticles tailored to a variety of biomedical applications ranging from
      cancer hyperthermia to remote control of gene expression. 

PMID- 24016042
TI  - Breaking bonds with electrons and protons. Models and examples.
AB  - Besides its theoretical interest, the attention currently aroused by proton
      coupled electron transfers (PCET reactions) has two main motives. One is a better
      understanding of biological processes in which PCET reactions are involved,
      Photosystem II as well as a myriad of other natural systems. The other is
      directed toward synthetic processes, many of which are related to global energy
      challenges. Until recently, the analyses of the mechanism and reactivity of PCET
      reactions have focused on outersphere transfers, those in which no bond between
      heavy atoms (all atoms with the exception of H) is concomitantly formed or
      broken. Conversely, reactions in which electron transfer triggers the breaking of
      a heavy-atom bond with no proton transfer have been extensively analyzed, both
      theoretically and experimentally. In both cases, strategies have been developed
      to distinguish between stepwise and concerted pathways. In each case, kinetic
      models have been devised, allowing the relation between activation and
      thermodynamic driving force to be established by means of parameters pertaining
      to the initial and final state. Although many natural and artificial processes
      include electron transfer, proton transfer, and heavy-atom bond breaking
      (/formation), no means were offered until recently to analyze the mechanism of
      such reactions, notably to establish the degree of concertedness of the three
      constitutive events. Likewise, no kinetic models were available to describe
      reactions where the three events are concerted. In this Account, we discuss the
      strategies to distinguish stepwise, partially concerted (when two of the three
      events are concerted), and totally concerted pathways in these reactions that
      include electron transfer, proton transfer, and heavy-atom bond breaking. These
      mechanism analysis methods are illustrated and validated by three examples. First
      we describe the electrochemical cleavage of an O-O bond in an aliphatic peroxide
      molecule with a pendant carboxylic acid group that can serve as proton donor for
      electron transfer and bond breaking. In the second example, we examine the
      breaking of one of the C-O bonds of CO2 within a multistep process where the
      reduction of CO2 into CO is catalyzed by an electrogenerated iron(0) porphyrin in
      the presence of various Bronsted acids. In this case, an intramolecular electron
      transfer triggers proton transfer and bond cleavage. In the first two examples,
      all three events are concerted. The third example also involves catalysis. It
      describes the cleavage of a cobalt-carbon bond in the reduction of
      chloroacetonitrile catalyzed by an electrogenerated cobalt(I) porphyrin. It
      illustrates the rather common case where the intermediate formed by the reaction
      of a transition metal complex with the substrate has to be cleaved to close the
      catalytic cycle. In the first two examples, all three events are concerted,
      whereas, in the last case, a partially concerted pathway takes place: proton
      transfer and bond-breaking (Co-C cleavage) are concerted after an initial
      electron transfer step. The all-concerted cases require a model that connects the
      kinetics to the thermodynamic driving force of the reaction. Starting from
      previous models of outersphere electron transfer, concerted proton-electron
      transfer, and concerted dissociative electron transfer, we describe a model for
      all-concerted proton-electron-bond breaking reactions. These pathways skip the
      high-energy intermediates that occur in stepwise pathways, but could introduce
      kinetic penalties. The all-concerted model allows one to assess these penalties
      and the way in which they can be fought by the supplement of driving force
      offered by concerted proton transfer. 

PMID- 24016040
TI  - Induction of mitochondrial dependent apoptosis and cell cycle arrest in human
      promyelocytic leukemia HL-60 cells by an extract from Dorstenia psilurus: a spice
      from Cameroon.
AB  - BACKGROUND: The use of edible plants is an integral part of dietary behavior in
      the West region of Cameroon. Dorstenia psilurus (Moraceae) is widely used as
      spice and as medicinal plant for the treatment of several diseases in Cameroon.
      The aim of this study is to investigate the cytotoxic and apoptotic potential of
      methanol extract of D. psilurus in human promyelocytic leukemia (HL-60) cells and
      prostate cancer (PC-3) cells. METHODS: Cytotoxicity of D. psilurus extract was
      tested in HL-60 and PC-3 cells using 3-(4, 5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) reduction assay and flow cytometric methods
      RESULTS: The methanol extract of D. psilurus have significant in vitro cytotoxic
      activity in HL-60 cells and PC-3 cells with IC50 value of 12 +/- 1.54 MUg/ml and
      18 +/- 0.45 MUg/ml respectively after 48 h. The mechanism of antiproliferative
      activity showed that after 24 h, D. psilurus extract induces apoptosis on HL-60
      cells by the generation of reactive oxygen species (ROS) along with concurrent
      loss of mitochondrial membrane potential, modification in the DNA distribution
      and enhance of G2/M phase cell cycle. CONCLUSION: The extract induces apoptosis
      of HL-60 cells associated with ROS production, loss of mitochondrial membrane
      potential and apoptotic DNA fragmentation.

PMID- 24016043
TI  - riDOM, a cell-penetrating peptide. Interaction with DNA and heparan sulfate.
AB  - DNA condensation in the presence of polycationic molecules is a well-known
      phenomenon exploited in gene delivery. riDOM (retro-inverso dioleoylmelittin) is
      a cell-penetrating peptide with excellent transporter properties for DNA. It is a
      chimeric molecule where ri-melittin is fused to dioleoylphosphoethanolamine. The
      physical-chemical properties of riDOM in solution and in the presence of DNA and
      heparan sulfate were investigated with spectroscopic and thermodynamic methods.
      Dynamic light scattering shows that riDOM in solution aggregates to well-defined
      nanoparticles with a diameter of ~13 nm and a zeta-potential of 22 mV, composed
      of about 220-270 molecules. Binding of riDOM to DNA was studied with dynamic
      light scattering, zeta-potential measurements, and isothermal titration
      calorimetry and was compared with authentic melittin-DNA interaction. riDOM binds
      tightly to DNA with a microscopic binding constant of 5 * 10(7) M(-1) and a
      stoichiometry of 12 riDOM per 10 DNA base pairs. In the complex the DNA double
      strand is completely shielded by the more hydrophobic riDOM molecules. Authentic
      melittin binds to DNA with a much lower binding constant of 5 * 10(6) M(-1) and
      lower stoichiometry of 5 melittin per 10 DNA base pairs. The binding enthalpies
      for riDOM and melittin are small and the binding reactions are entropy-driven.
      Sulfated glycosaminoglycans such as heparan sulfate are also linear molecules
      with a negative charge. riDOM binding to heparan sulfate on cell surfaces can
      therefore interfere with DNA-riDOM binding. riDOM-heparan sulfate complex
      formation was characterized by isothermal titration calorimetry and spectroscopic
      methods. The binding constant of riDOM for heparan sulfate is K ~ 2 * 10(6) M(
      1). Authentic melittin has a similar binding constant but riDOM shows a 3-fold
      higher packing density on heparan sulfate than the distinctly smaller melittin. 

PMID- 24016045
TI  - The hunt for nonpulmonary vein triggers and acute pulmonary vein reconnections.

PMID- 24016046
TI  - Association of Type D personality with the autonomic and hemodynamic response to
      the cold pressor test.
AB  - Mechanisms relating Type D personality to poor health are largely unknown, with
      autonomic nervous system function being a candidate. This study examined the
      physiologic response to cold stress. Undergraduates (N = 101, 84% female)
      underwent a cold pressor test. An electrocardiogram, impedance cardiogram, and
      blood pressure were recorded. Type D personality was assessed by self-report
      questionnaire. Type D was associated with increased systolic and diastolic blood
      pressure reactivity. Exploratory analyses showed Type D men to respond with
      increased respiratory sinus arrhythmia (i.e., higher parasympathetic activity),
      and decreased pre-ejection period (i.e., larger sympathetic activity), while Type
      D women showed a reciprocal response pattern. In conclusion, Type D personality
      was associated with an exaggerated hemodynamic response to cold stress, which may
      contribute to an increased risk of hypertension in Type D individuals. 

PMID- 24016047
TI  - Addressing the impact factors of nursing education journals.

PMID- 24016049
TI  - Poetic forms: shaping aesthetic knowing.

PMID- 24016048
TI  - Google+ gets an A+ in distance education.

PMID- 24016050
TI  - Timing of dialysis initiation in acute kidney injury and acute-on-chronic renal
      failure.
AB  - The decision to provide dialytic support and choosing the ideal moment to
      initiate therapy are common impasses for physicians treating patients with acute
      kidney injury (AKI). Although renal replacement therapy (RRT) has been
      extensively used in clinical practice for more than 30 years, there is a paucity
      of evidence to guide clinicians on the optimal utilization of RRT in AKI. In the
      absence of traditional or urgent indications, there is no consensus on whether
      dialysis should be offered and when it should be started. The lack of agreed-upon
      parameters to guide the decision, the fear of the risk of the procedure, and the
      possible contribution to worse prognosis with RRT have resulted in a considerable
      variation in practice among physicians and centers. In this review, we summarize
      the evidence evaluating time of initiation of RRT and discuss possible approaches
      for future trials in addressing this issue.

PMID- 24016055
TI  - An investigation of the effect of athletes' age on the coaching behaviours of
      professional top-level youth soccer coaches.
AB  - The aim of the study was to investigate the behaviours, cognitive processes and
      practice activities of 12 English youth professional soccer coaches across 6
      different age groups. Systematic observation data were collected using a modified
      version of the Coach Analysis and Intervention System which provided a detailed
      analysis of coaching behaviours performed during practice. Interpretive
      interviews were then triangulated with the behavioural data to identify the
      cognitive processes underlying the behaviours performed. The behavioural results
      showed that the coaches of the younger age groups used more instruction and the
      coaches of the older age groups used more divergent questioning and significantly
      more total feedback and punitive behaviours. The coaches of the younger age
      groups used more training form activities than the coaches of the older age
      groups who used more playing form activities. However, the interviews revealed
      that instead of the age of athletes' directly affecting the cognitive process of
      coaches it was in fact the coaches underlying beliefs about coaching, their
      previous experiences and perceived pressures from the context that determined the
      behaviours performed.

PMID- 24016056
TI  - Effect of player position on movement behaviour, physical and physiological
      performances during an 11-a-side football game.
AB  - The aim of this study was to identify differences in time-motion, modified
      training impulse, body load and movement behaviour between defenders, midfielders
      and forwards, during an 11-a-side simulated football game. Twenty elite youth
      male footballers from the same squad participated in this study (age: 18.1 +/-
      0.7 years old, body mass: 70.5 +/- 4.3 kg, height: 1.8 +/- 0.3 m and playing
      experience: 9.4 +/- 1.3 years). All data were collected using GPS units (SPI-Pro,
      GPSports, Canberra, Australia). The movement behaviour was measured with
      kinematic data, used to calculate position-specific centroids (defenders,
      midfielders and forwards), and processed with non-linear statistical procedures
      (approximate entropy normalised and relative phase). There were significant
      effects and interactions in all variables across the players' positions. The
      results showed that displacements of all players (defenders, midfielders and
      forwards) were nearer and more coordinated with their own position-specific
      centroids than with the other centroids. However, this coupling effect was
      stronger in midfield players and weaker in forwards. All players' dynamical
      positioning showed more irregularity when related to the forwards' centroid, as a
      consequence of their need to be less predictable when playing. The time-motion
      and physiological variables showed lower activity in forward players. Adding
      together, the results may contribute to a better understanding of players'
      specific performances and football complexity.

PMID- 24016057
TI  - Vermelhotin, an anti-inflammatory agent, suppresses nitric oxide production in
      RAW 264.7 cells via p38 inhibition.
AB  - Vermelhotin exhibited potential anti-inflammatory activity through inhibition of
      nitric oxide production (IC50 = 5.35 +/- 0.59 MUM) in LPS-stimulated RAW 264.7
      macrophage cells. Vermelhotin suppressed expression of inducible nitric oxide
      synthase (iNOS) at mRNA and protein levels, in a dose-dependent manner.
      Mechanistic studies revealed that vermelhotin abrogated upstream signaling of
      iNOS expression by selectively inhibiting p38 phosphorylation, while ERK and JNK
      activations were not affected.

PMID- 24016059
TI  - A hybrid microbial fuel cell membrane bioreactor with a conductive
      ultrafiltration membrane biocathode for wastewater treatment.
AB  - A new hybrid, air-biocathode microbial fuel cell-membrane bioreactor (MFC-MBR)
      system was developed to achieve simultaneous wastewater treatment and
      ultrafiltration to produce water for direct reclamation. The combined advantages
      of this system were achieved by using an electrically conductive ultrafiltration
      membrane as both the cathode and the membrane for wastewater filtration. The MFC
      MBR used an air-biocathode, and it was shown to have good performance relative to
      an otherwise identical cathode containing a platinum catalyst. With 0.1 mm
      prefiltered domestic wastewater as the feed, the maximum power density was 0.38
      W/m(2) (6.8 W/m(3)) with the biocathode, compared to 0.82 W/m(2) (14.5 W/m(3))
      using the platinum cathode. The permeate quality from the biocathode reactor was
      comparable to that of a conventional MBR, with removals of 97% of the soluble
      chemical oxygen demand, 97% NH3-N, and 91% of total bacteria (based on flow
      cytometry). The permeate turbidity was <0.1 nephelometric turbidity units. These
      results show that a biocathode MFC-MBR system can achieve high levels of
      wastewater treatment with a low energy input due to the lack of a need for
      wastewater aeration. 

PMID- 24016060
TI  - Quantitative real-time imaging of protein-protein interactions by LSPR detection
      with micropatterned gold nanoparticles.
AB  - Localized surface plasmon resonance (LSPR) offers powerful means for sensitive
      label-free detection of protein-protein interactions in a highly multiplexed
      format. We have here established self-assembly and surface modification of
      plasmonic nanostructures on solid support suitable for quantitative protein
      protein interaction analysis by spectroscopic and microscopic LSPR detection.
      These architectures were obtained by layer-by-layer assembly via electrostatic
      attraction. Gold nanoparticles (AuNP) were adsorbed on a biocompatible amine
      terminated poly(ethylene glycol) (PEG) polymer brush and further functionalized
      by poly-l-lysine graft PEG (PLL-PEG) copolymers. Stable yet reversible protein
      immobilization was achieved via tris(nitrilotriacetic acid) groups incorporated
      into the PLL-PEG coating. Thus, site-specific immobilization of His-tagged
      proteins via complexed Ni(II) ions was achieved. Functional protein
      immobilization on the surface was confirmed by real-time detection of LSPR
      scattering by reflectance spectroscopy. Association and dissociation rate
      constants obtained for a reversible protein-protein interaction were in good
      agreement with the data obtained by other surface-sensitive detection techniques.
      For spatially resolved detection, AuNP were assembled into micropatterns by means
      of photolithographic uncaging of surface amines. LSPR imaging of reversible
      protein-protein interactions was possible in a conventional wide field
      microscope, yielding detection limits of ~30 protein molecules within a
      diffraction-limited surface area. 

PMID- 24016061
TI  - No association between sperm competition and sperm length variation across dung
      flies (Scathophagidae).
AB  - Sperm length is extremely variable across species, but a general explanation for
      this variation is lacking. However, when the risk of sperm competition is high,
      sperm length is predicted to be less variable within species, and there is some
      evidence for this in birds and social insects. Here, we examined intraspecific
      variation in sperm length, both within and between males, and its potential
      associations with sperm competition risk and variation in female reproductive
      tract morphology across dung flies. We used two measures of variation in sperm
      size, and testis size was employed as our index of sperm competition risk. We
      found no evidence of associations between sperm length variation and sperm
      competition or female reproductive tract variation. These results suggest that
      variation in sperm competition risk may not always be associated with variation
      in sperm morphology, and the cause(s) of sperm length variation in dung flies
      remains unclear. 

PMID- 24016062
TI  - Trichophyton erinacei kerion barbae from a hedgehog with direct osculatory
      transfer to another person.
AB  - We describe a case of kerion tinea barbae infection due to Trichophyton erinacei
      in a 37-year-old man. The infection had also been transferred to his partner by
      direct contact from kissing. T. erinacei is a zoophilic dermatophyte occasionally
      harboured by the hedgehog (Erinaceus europaeus). There are few reports of human
      infection in the literature, and it rarely causes a kerion. There is only one
      previous report of tinea barbae occurrence due to T. erinacei. This case
      highlights the possibility of one of the more unusual fungal infections that can
      be acquired in the UK, and highlights the necessity of asking specific questions
      to identify possible sources of infection.

PMID- 24016063
TI  - In vitro metabolites of di-2-ethylhexyl adipate (DEHA) as biomarkers of exposure
      in human biomonitoring applications.
AB  - Di-2-ethylhexyl adipate (DEHA) is a common plasticizer used in food packaging. At
      high doses, DEHA can cause adverse health effects in rats. Although the potential
      for human exposure to DEHA is high, no DEHA specific biomarkers are identified
      for human biomonitoring. Using human liver microsomes, we investigated the in
      vitro phase I metabolism of DEHA and its hydrolytic metabolite mono-2-ethylhexyl
      adipate (MEHA) and, for comparison purposes, of the analogous di-2-ethylhexyl
      phthalate (DEHP) and its hydrolytic metabolite mono-2-ethylhexyl phthalate. We
      unequivocally identified MEHA, a DEHA specific biomarker, and adipic acid, a
      nonspecific biomarker, using authentic standards. On the basis of their mass
      spectrometric fragmentation patterns, we tentatively identified two other DEHA
      specific metabolites: mono-2-ethylhydroxyhexyl adipate (MEHHA) and mono-2
      ethyloxohexyl adipate (MEOHA), analogous to the oxidative metabolites of DEHP.
      Interestingly, although adipic acid was the major in vitro metabolite of DEHA,
      the analogous phthalic acid was not the major in vitro metabolite of DEHP. Our
      preliminary data for 144 adults with no known exposure to DEHA suggests that
      adipic acid is also the main in vivo urinary metabolite, while MEHA, MEHHA, and
      MEOHA are only minor metabolites. Therefore, the use of these specific
      metabolites for assessing the exposure of DEHA may be limited to highly exposed
      populations. 

PMID- 24016064
TI  - Radiation recall following cisplatin chemotherapy.

PMID- 24016065
TI  - Fluorescent imaging of single nanoparticles and viruses on a smart phone.
AB  - Optical imaging of nanoscale objects, whether it is based on scattering or
      fluorescence, is a challenging task due to reduced detection signal-to-noise
      ratio and contrast at subwavelength dimensions. Here, we report a field-portable
      fluorescence microscopy platform installed on a smart phone for imaging of
      individual nanoparticles as well as viruses using a lightweight and compact opto
      mechanical attachment to the existing camera module of the cell phone. This hand
      held fluorescent imaging device utilizes (i) a compact 450 nm laser diode that
      creates oblique excitation on the sample plane with an incidence angle of ~75
      degrees , (ii) a long-pass thin-film interference filter to reject the scattered
      excitation light, (iii) an external lens creating 2* optical magnification, and
      (iv) a translation stage for focus adjustment. We tested the imaging performance
      of this smart-phone-enabled microscopy platform by detecting isolated 100 nm
      fluorescent particles as well as individual human cytomegaloviruses that are
      fluorescently labeled. The size of each detected nano-object on the cell phone
      platform was validated using scanning electron microscopy images of the same
      samples. This field-portable fluorescence microscopy attachment to the cell
      phone, weighing only ~186 g, could be used for specific and sensitive imaging of
      subwavelength objects including various bacteria and viruses and, therefore,
      could provide a valuable platform for the practice of nanotechnology in field
      settings and for conducting viral load measurements and other biomedical tests
      even in remote and resource-limited environments.

PMID- 24016066
TI  - The human resource information system: a rapid appraisal of Pakistan's capacity
      to employ the tool.
AB  - BACKGROUND: Human resources are an important building block of the health system.
      During the last decade, enormous investment has gone into the information systems
      to manage human resources, but due to the lack of a clear vision, policy, and
      strategy, the results of these efforts have not been very visible. No reliable
      information portal captures the actual state of human resources in Pakistan's
      health sector. The World Health Organization (WHO) has provided technical support
      for the assessment of the existing system and development of a comprehensive
      Human Resource Information System (HRIS) in Pakistan. METHODS: The questions in
      the WHO-HRIS Assessment tool were distributed into five thematic groups.
      Purposively selected (n=65) representatives from the government, private sector,
      and development partners participated in this cross sectional study, based on
      their programmatic affiliations. RESULTS: Fifty-five percent of organizations and
      departments have an independent Human Resources (HR) section managed by an
      establishment branch and are fully equipped with functional computers. Forty-five
      organizations (70%) had HR rules, regulations and coordination mechanisms, yet
      these are not implemented. Data reporting is mainly in paper form, on prescribed
      forms (51%), registers (3%) or even plain papers (20%). Data analysis does not
      give inputs to the decision making process and dissemination of information is
      quite erratic. Most of the organizations had no feedback mechanism for cross
      checking the HR data, rendering it unreliable. CONCLUSION: Pakistan is lacking
      appropriate HRIS management. The current HRIS indeed has a multitude of problems.
      In the wake of 2011 reforms within the health sector, provinces are even in a
      greater need for planning their respective health department services and must
      work on the deficiencies and inefficiencies of their HRIS so that the gaps and HR
      needs are better aligned for reaching the 2015 UN Millennium Development Goals
      (MDGs) targets.

PMID- 24016067
TI  - Distractor devaluation in a flanker task: object-specific effects without
      distractor recognition memory.
AB  - Previous research has shown that ignored stimuli are affectively devalued (i.e.,
      distractor devaluation effect). Whereas previous research used feature-based
      selection tasks to investigate distractor devaluation, we used an object-based
      paradigm, allowing us to investigate open questions regarding underlying
      mechanisms. First, by using an object-based paradigm, we expected to find
      distractor devaluation for specific distractors (in contrast to general effects
      for certain categories). Second, we expected distractor devaluation in the
      absence of explicit recall of the to-be-evaluated stimulus' prior status (e.g.,
      distractor), which is an important and previously untested factor, in order to
      exclude alternative explanations for distractor devaluation. Third, derived from
      the devaluation-by-inhibition hypothesis, we predicted that conditions of
      stronger distractor interference would result in stronger distractor devaluation.
      These predictions were confirmed in two experiments. We thus provide evidence
      that distractor devaluation can be a consequence of selective attention processes
      and that the evaluative consequences of ignoring can be tied to the mental
      representation of specific distractors.

PMID- 24016068
TI  - Interactions between social/ behavioral factors and ADRB2 genotypes may be
      associated with health at advanced ages in China.
AB  - BACKGROUND: Existing literature indicates that ADRB2 gene is associated with
      health and longevity, but none of previous studies investigated associations of
      carrying the ADRB2 minor alleles and interactions between ADRB2 genotypes and
      social/behavioral factors(GxE) with health outcomes at advanced ages. This study
      intends to fill in this research gap. METHOD: We conducted an exploratory
      analysis, using longitudinal survey phenotype/genotype data from 877 oldest-old
      aged 90+. To estimate association of GxE interactions with health outcome,
      adjusted for the potential correlation between genotypes and social/behavioral
      factors and various other potentially confounding factors, we develop and test an
      innovative three-step procedure which combines logistic regression and structural
      equation methods. RESULTS: Interaction between regular exercise and carrying
      rs1042718 minor allele is significantly and positively associated with good
      cognitive function; interaction between regular exercise and carrying rs1042718
      or rs1042719 minor allele is significantly and positively associated with self
      reported good health; and interaction between social-leisure activities and
      carrying rs1042719 minor allele is significantly and positively associated with
      self-reported good health. Carrying rs1042718 or rs1042719 minor alleles is
      significantly and negatively associated with negative emotion, but the ADRB2 SNPs
      are not significantly associated with cognitive function and self-reported
      health. Our structural equation analysis found that, adjusted for the confounding
      effects of correlation of the ADRB2 SNPs with negative emotion, interaction
      between negative emotion and carrying rs1042718 or rs1042719 minor allele is
      significantly and negatively associated with cognitive function. The positive
      association of regular exercise and social-leisure activities with cognitive
      function and self-reported health, and negative association of negative emotion
      with cognitive function, were much stronger among carriers of rs1042718 or
      rs1042719 alleles, compared to the non-carriers. CONCLUSIONS: The results
      indicate significant positive associations of interactions between
      social/behavioral factors and the ADRB2 genotypes with health outcomes of
      cognitive function and self-reported health, and negative associations of
      carrying rs1042718 or rs1042719 minor alleles with negative emotion, at advanced
      ages in China. Our findings are exploratory rather than causal conclusions. This
      study implies that near-future health promotion programs considering individuals'
      genetic profiles, with appropriate protection of privacy/confidentiality, would
      yield increased benefits and reduced costs to the programs and their
      participants.

PMID- 24016069
TI  - Pimavanserin for the treatment of Parkinson's disease psychosis.
AB  - INTRODUCTION: Parkinson's disease (PD) is a neurobehavioral disorder defined by
      its motor features. Its treatment is frequently complicated by the presence of
      psychotic symptoms, most prominently hallucinations and delusions. These cause
      major distress and are the primary cause for nursing home placement. Current
      treatment requires either a reduction in medications for mobility or the addition
      of atypical antipsychotics, none of which are approved in the United States, and
      which are associated with major potential drawbacks. AREAS COVERED: Information
      from extensive personal experience, a Pubmed literature search plus a direct
      request to Acadia Pharmaceuticals was used for this review. A brief review of the
      clinical problem and its current state of treatment will be followed by a
      discussion of pimavanserin and its potential role in treating PD psychosis (PDP).
      Several observations have implicated serotonin in the physiology of psychotic
      symptoms. Lysergic acid diethylamide, phencyclidine, and similar drugs that
      activate 5HT2A serotonin receptors produce psychotic syndromes, and almost all
      antipsychotic neuroleptics share the property of blocking the 5HT2A receptor as
      well as the dopamine D2 receptor. The reduced motor side effects of the second
      generation antipsychotics have been ascribed to these drugs having greater 5HT2A
      antagonism than the first generation. Studies in animal models of psychosis have
      suggested benefits from drugs blocking the 5HT2A receptor alone without the motor
      side effects seen with D2 receptor antagonism. EXPERT OPINION: Pimavanserin, a
      5HT2A inverse agonist, has no motor side effects, and a remarkable safety profile
      that is comparable to placebo. Its antipsychotic effects coupled with its lack of
      motor side effects could make it an ideal drug for treating psychotic symptoms in
      PD, a major unmet need. One Phase III trial in PDP has demonstrated excellent
      tolerability and significant benefit. The FDA agreed to the filing of a planned
      new drug approval (NDA) for an indication in the treatment of PDP.

PMID- 24016071
TI  - CellMinerHCC: a microarray-based expression database for hepatocellular carcinoma
      cell lines.
AB  - BACKGROUND & AIMS: Therapeutic options for hepatocellular carcinoma (HCC) still
      remain limited. Development of gene targeted therapies is a promising option. A
      better understanding of the underlying molecular biology is gained in in vitro
      experiments. However, even with targeted manipulation of gene expression varying
      treatment responses were observed in diverse HCC cell lines. Therefore,
      information on gene expression profiles of various HCC cell lines may be crucial
      to experimental designs. To generate a publicly available database containing
      microarray expression profiles of diverse HCC cell lines. METHODS: Microarray
      data were analyzed using an individually scripted R program package. Data were
      stored in a PostgreSQL database with a PHP written web interface. Evaluation and
      comparison of individual cell line expression profiles are supported via public
      web interface. RESULTS: This database allows evaluation of gene expression
      profiles of 18 HCC cell lines and comparison of differential gene expression
      between multiple cell lines. Analysis of commonly regulated genes for signaling
      pathway enrichment and interactions demonstrates a liver tumor phenotype with
      enrichment of major cancer related KEGG signatures like 'cancer' and
      'inflammatory response'. Further molecular associations of strong scientific
      interest, e.g. 'lipid metabolism', were also identified. CONCLUSIONS: We have
      generated CellMinerHCC (http://www.medicalgenomics.org/cellminerhcc), a publicly
      available database containing gene expression data of 18 HCC cell lines. This
      database will aid in the design of in vitro experiments in HCC research, because
      the genetic specificities of various HCC cell lines will be considered.

PMID- 24016072
TI  - Dual Atrial Tachycardia in a Transplant Heart: When is "In" Really "Out"?

PMID- 24016073
TI  - Are bidentate ligands really better than monodentate ligands for nanoparticles?
AB  - Coordinating ligands are widely used to vary the solubility and reactivity of
      nanoparticles for subsequent bioconjugation. Although long-term colloidal
      stability is enhanced by using bidentate coordinating ligands over monodentate
      ones, other properties such as nonspecific adsorption of target molecules and
      ligand exchange have not been quantified. In this study, we modified a near
      infrared dye to serve as a highly sensitive reporter for nonspecific binding of
      thiolated target molecules to nanoparticle surfaces that are functionalized with
      monodentate or bidentate coordinated ligands. Specifically, we analyzed
      nonspecific binding mechanisms to quantum dots (QDs) by fitting the adsorption
      profiles to the Hill equation and the parameters are used to provide a
      microscopic picture of how ligand density and lability control nonspecific
      adsorption. Surprisingly, bidentate ligands are worse at inhibiting adsorption to
      QD surfaces at low target/QD ratios, although they become better as the ratio
      increases, but only if the nanoparticle surface area is large enough to overcome
      steric effects. This result highlights that a balance between ligand density and
      lability depends on the dentate nature of the ligands and controls how molecules
      in solution can coordinate to the nanoparticle surface. These results will have
      major implications for a range of applications in nanobiomedicine,
      bioconjugation, single molecule spectroscopy, self-assembly, and
      nano(photo)catalysis where both nonspecific and specific surface interactions
      play important roles. As an example, we tested the ability of monodentate and
      bidentate functionalized nanoparticles to resist nonspecific adsorption of IgG
      antibodies that contained free thiol groups at a 1:1 QD/IgG ratio and found that
      QDs with monodentate ligands did indeed result in lower nonspecific adsorption. 

PMID- 24016075
TI  - Regularity encoding and deviance detection of frequency modulated sweeps: human
      middle- and long-latency auditory evoked potentials.
AB  - Fast encoding of frequency modulated (FM) sweeps is crucial for communication. In
      humans, FM sweeps deviating from the acoustic regularity elicit the mismatch
      negativity (MMN) evoked potential. Yet, direction sensitivity to FM sweeps is
      found in animals' primary auditory cortex, upstream of MMN sources found in
      humans. Here, we were interested in whether direction deviants of complex FM
      sweeps modulated brain responses earlier than MMN. We used a controlled oddball
      paradigm, and measured the middle latency responses (MLRs) and the MMN. Our
      results showed a repetition enhancement to the standards at the Pa component of
      the MLR and a genuine MMN in the later response range. These results show that,
      early in the cortical hierarchy, the system is sensitive to the physical
      characteristics of the repetitive stimuli, but a higher-order mechanism is needed
      to detect violations of the acoustic regularity. 

PMID- 24016074
TI  - Brief intervention and decrease of alcohol consumption among women: a systematic
      review.
AB  - Problems related to alcohol consumption are priority public health issues
      worldwide and may compromise women's health. The early detection of risky alcohol
      consumption combined with a brief intervention (BI) has shown promising results
      in prevention for different populations. The aim of this study was to examine
      data from recent scientific publications on the use of BI toward reducing alcohol
      consumption among women through a systematic review. Electronic searches were
      conducted using Web of Science, PubMed(Medline) and PsycInfo databases. In all
      databases, the term "brief intervention" was associated with the words "alcohol"
      and "women", and studies published between the years 2006 and 2011 were selected.
      Out of the 133 publications found, the 36 scientific articles whose central theme
      was performing and/or evaluating the effectiveness of BI were included. The full
      texts were reviewed by content analysis technique. This review identified
      promising results of BI for women, especially pregnant women and female college
      students, in different forms of application (face-to-face, by computer or
      telephone) despite a substantial heterogeneity in the clinical trials analyzed.
      In primary care, which is a setting involving quite different characteristics,
      the results among women were rather unclear. In general, the results indicated a
      decrease in alcohol consumption among women following BI, both in the number of
      days of consumption and the number of doses, suggesting that the impact on the
      woman's reproductive health and the lower social acceptance of female consumption
      can be aspects favorable for the effectiveness of BI in this population. 

PMID- 24016076
TI  - Timing of return to dialysis in patients with failing kidney transplants.
AB  - In the last decade, the number of patients starting dialysis after a failed
      kidney transplant has increased substantially. These patients appear to be
      different from their transplant-naive counterparts, and so may be the timing of
      dialysis therapy initiation. An increasing number of studies suggest that in
      transplant-naive patients, later dialysis initiation is associated with better
      outcomes. Very few data are available on timing of dialysis reinitiation in
      failed transplant recipients, and they suggest that an earlier return to dialysis
      therapy tended to be associated with worse survival, especially among healthier
      and younger patients and women. Failed transplant patients may also have unique
      issues such as continuation of immunosuppression versus withdrawal or the need
      for remnant allograft nephrectomy with regard to dialysis reinitiation. These
      patients may have a different predialysis preparation work-up, worse blood
      pressure control, higher or lower serum phosphorus levels, lower serum
      bicarbonate concentration, and worse anemia management. The choice of dialysis
      modality may also represent an important question for these patients, even though
      there appears to be no difference in mortality between patients starting
      peritoneal versus hemodialysis. Finally, failed transplant patients returning to
      dialysis appear to have a higher mortality rate compared with transplant-naive
      incident dialysis patients, especially in the first several months of dialysis
      therapy. In this review, we will summarize the available data related to the
      timing of dialysis initiation and outcomes in failed kidney transplant patients
      after returning to dialysis.

PMID- 24016097
TI  - Physiological assessment of isolated running does not directly replicate running
      capacity after triathlon-specific cycling.
AB  - Triathlon running is affected by prior cycling and power output during triathlon
      cycling is variable in nature. We compared constant and triathlon-specific
      variable power cycling and their effect on subsequent submaximal running
      physiology. Nine well-trained male triathletes (age 24.6 +/- 4.6 years, [Formula:
      see text] 4.5 +/- 0.4 L . min(-1); mean +/- SD) performed a submaximal
      incremental run test, under three conditions: no prior exercise and after a 1 h
      cycling trial at 65% of maximal aerobic power with either a constant or a
      variable power profile. The variable power protocol involved multiple 10-90 s
      intermittent efforts at 40-140% maximal aerobic power. During cycling, pulmonary
      ventilation (22%, +/- 14%; mean; +/- 90% confidence limits), blood lactate (179%,
      +/- 48%) and rating of perceived exertion (7.3%, +/- 10.2%) were all
      substantially higher during variable than during constant power cycling. At the
      start of the run, blood lactate was 64%, +/- 61% higher after variable compared
      to constant power cycling, which decreased running velocity at 4 mM lactate
      threshold by 0.6, +/- 0.9 km . h(-1). Physiological responses to incremental
      running are negatively affected by prior cycling and, to a greater extent, by
      variable compared to even-paced cycling. Testing and training of triathletes
      should account foe higher physiological cost of triathlon-specific cycling and
      its effect on subsequent running.

PMID- 24016098
TI  - Validation of maturity offset in a longitudinal sample of Polish boys.
AB  - Abstract This study attempted to validate an anthropometric equation for
      predicting age at peak height velocity (APHV) in 193 Polish boys followed
      longitudinally 8-18 years (1961-1972). Actual APHV was derived with Preece-Baines
      Model 1. Predicted APHV was estimated at each observation using chronological age
      (CA), stature, mass, sitting height and estimated leg length. Mean predicted APHV
      increased from 8 to 18 years. Actual APHV was underestimated at younger ages and
      overestimated at older ages. Mean differences between predicted and actual APHV
      were reasonably stable between 13 and 15 years. Predicted APHV underestimated
      actual APHV 3 years before, was almost identical with actual age 2 years before,
      and then overestimated actual age through 3 years after PHV. Predicted APHV did
      not differ among boys of contrasting maturity status 8-11 years, but diverged
      among groups 12-15 years. In conclusion, predicted APHV is influenced by CA and
      by early and late timing of actual PHV. Predicted APHV has applicability among
      average maturing boys 12-16 years in contrast to late and early maturing boys.
      Dependence upon age and individual differences in actual APHV limits utility of
      predicted APHV in research with male youth athletes and in talent programmes.

PMID- 24016100
TI  - In situ generation of functionality in a reactive haloalkane-based ligand for the
      design of new porous coordination polymers.
AB  - Herein, we report new porous coordination polymers (PCPs) via a facile synthetic
      approach called "in situ generation of functionality in the ligand". Upon a
      synthetic process of PCPs, a neutral (-CH2OH) or a cationic functionality (-CH2
      [4,4'-bipyridine](+)) was generated on a isophthalate ligand from a reactive
      haloalkane (-CH2Br) moiety, affording two new PCPs. The PCPs have two-dimensional
      layered structures with large potential solvent-accessible voids for CO2
      adsorption. 

PMID- 24016099
TI  - Apratoxin H and apratoxin A sulfoxide from the Red Sea cyanobacterium Moorea
      producens.
AB  - Cultivation of the marine cyanobacterium Moorea producens, collected from the
      Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new
      apratoxin analogues apratoxin H (1) and apratoxin A sulfoxide (2), together with
      the known apratoxins A-C, lyngbyabellin B, and hectochlorin. The absolute
      configuration of these new potent cytotoxins was determined by chemical
      degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic
      acid in place of the proline residue present in apratoxin A, expanding the known
      suite of naturally occurring analogues that display amino acid substitutions
      within the final module of the apratoxin biosynthetic pathway. The oxidation site
      of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR
      data, and 2 could not be generated experimentally by oxidation of apratoxin A.
      The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC50 = 3.4 and
      89.9 nM, respectively) provides further insight into the structure-activity
      relationships in the apratoxin series. Phylogenetic analysis of the apratoxin
      producing cyanobacterial strains belonging to the genus Moorea, coupled with the
      recently annotated apratoxin biosynthetic pathway, supports the notion that
      apratoxin production and structural diversity may be specific to their
      geographical niche.

PMID- 24016101
TI  - Fresh Pork and Porcine Reproductive and Respiratory Syndrome Virus: Factors
      Related to the Risk of Disease Transmission.
AB  - Porcine reproductive and respiratory syndrome virus (PRRS) is a highly infectious
      virus. Experimentally, the disease can be induced in naive pigs by the oral,
      intranasal and intramuscular routes. Depending on the virulence of the strain of
      the virus and the age of the pig, peak viremia can occur within 7 days of
      infection, and live virus can be isolated from blood or lymph nodes for several
      months post-infection. Young pigs tend to develop higher titres of viremia than
      older pigs infected by the same route and dose with the same strain of virus.
      Porcine reproductive and respiratory syndrome virus survives in pork harvested
      from infected pigs for extended periods at temperatures of -20 or -70 degrees C.
      In experimentally infected pigs, survival of PRRS virus in muscle held at 4
      degrees C has been demonstrated for at least 7 days, and infectivity of the virus
      in these samples was confirmed by bioassay. The optimal pH range for the survival
      of PRRS virus is thought to be 6.0 to 7.5. The elevated pH of non-meat tissues
      (generally one pH unit higher) is likely to favour extended survival of PRRS
      virus in pig carcasses from which all superficial and deep lymph nodes have not
      been removed. It is likely that exsanguinated carcasses held at 4 degrees C
      retain sufficient blood or lymph tissue to contain infective doses of PRRS virus.
      Porcine reproductive and respiratory syndrome virus is rapidly inactivated by
      heat, providing a predictable method to ensure that pork tissues are free of
      viable virus and feeding of cooked swill or garbage should not constitute a risk
      to pigs. While the probability of viable PRRS virus being present in a pig
      carcass may be low, the risk is not zero. The importation of raw pork into
      countries where PRRS is not endemic represents a hazard with potentially severe
      economic consequences.

PMID- 24016102
TI  - Investigation of potential markers of acid resistance in Lactobacillus plantarum
      by comparative proteomics.
AB  - AIMS: To investigate cell determinants of resistance to gastric acidity in
      Lactobacillus plantarum using comparative proteomics. METHODS AND RESULTS: Among
      ten Lact. plantarum strains that were tested for their acid resistance in vitro,
      three strains with different phenotypes were selected for comparative proteomic
      analysis: LC 804 (resistant), CIP A159 (intermediate) and CECT 4185 (sensitive).
      Constitutive differences between whole-cell proteomes of the three strains were
      studied. Among the differentially expressed proteins between strains, 17 have
      previously been reported to be involved in acid resistance processes. The effect
      of a low-pH exposure on these proteomic patterns was investigated, which led to
      the identification of five putative determinants of acid resistance (heat-shock
      protein GrpE, methionine synthase and 30S ribosomal protein S2) or sensitivity
      (phosphotransacetylase and adenylosuccinate synthase). Analysis also revealed
      three additional proteins involved in cell envelope biogenesis (3-oxoacyl
      synthase II, dTDP-glucose 4,6-dehydratase and dTDP-4-dehydrorhamnose 3,5
      epimerase) likely to be key factors of intrinsic acid tolerance in Lact.
      plantarum. CONCLUSIONS: The approach used in this study enabled the
      identification of potential markers of acid tolerance in Lact. plantarum, which
      may serve for phenotyping and screening purposes. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The present work represents a further step towards the identification of
      bacterial biomarkers for each particular probiotic feature.

PMID- 24016103
TI  - Identification of rice proteins recognized by the IgE antibodies of patients with
      food allergies.
AB  - Similarity among food allergens is a great problem affecting the specificity of
      diagnosis and treatment of allergic patients. We have observed that 80% of
      patients with food (including wheat) and pollen allergies have increased IgE
      antibodies against rice proteins. By immunoblotting, we documented that boiling
      decreased solubility and IgE reactivity of PBS-extracted rice and wheat proteins,
      yet in SDS extracts this reactivity was only slightly changed. The sera of
      patients highly positive on the IgE immunoblot and positive in basophil
      activation and skin prick test with boiled rice components were used for
      characterizing the IgE-binding proteins separated by 1D or 2D electrophoresis.
      Using mass spectrometry, we identified 22 rice SDS soluble proteins. Six of them
      were new thermostable potential rice allergens: glutelin C precursor, granule
      bound starch synthase 1 protein, disulfide isomerase-like 1-1 protein,
      hypothetical protein OsI_13867, putative acid phosphatase precursor 1, and a
      protein encoded by locus Os02g0453600. All of the identified rice proteins
      differed from known wheat allergens, except proteins belonging to the alpha
      amylase/trypsin inhibitor family. Furthermore, we would suggest that in patients
      with high IgE reactivity to wheat and rice components, the IgE immunoblot and
      skin prick test with boiled rice proteins could be beneficial before diet
      recommendation. 

PMID- 24016104
TI  - Multiple clustered dermatofibromas (fibrous histiocytomas): an atypical clinical
      variant of dermatofibroma.

PMID- 24016105
TI  - Pharmacokinetics of CNT-based drug delivery systems.
AB  - Carbon nanotubes (CNT) are allotropes of carbon with a cylindrical nanostructure.
      They have recently aroused great interests as drug carriers, but their
      pharmacokinetic profiles which determine their potentials in clinical application
      are yet to be fully understood. Therefore, this overview attempts to outline the
      processes of absorption, distribution, metabolism and excretion (ADME) that
      govern the pharmacokinetics of CNT. In addition, the molecular mechanisms of
      intracellular internalization and drug release are also discussed. 

PMID- 24016106
TI  - Pharmacokinetics of polymeric micelles for cancer treatment.
AB  - Polymeric micelles (PMs) have shown promising applications for the drug delivery
      since they can improve the low water solubility of hydrophobic drugs, reduce
      toxicity of the drug, protect unstable drugs from degradation or metabolism, and
      prolong the time of blood circulation. The incorporation of drugs to PMs can
      fundamentally alter the drug's pharmacokinetics (PK) to enable their efficient
      therapeutic activity. This article reviews the key progress to date about the
      work of the PK of various PMs in oncology. First, the common techniques to
      incorporate the drugs to PMs have been introduced. The PK of PMs for typical anti
      tumor drugs (Taxels, Doxorubicin, Cisplatin, camptothecins) according to
      different amphiphilic polymers is discussed in detail. The strengths and
      limitations of PM formulations for the PK also have been included. 

PMID- 24016107
TI  - Toxicity of carbon nanotubes.
AB  - Carbon nanotubes (CNTs) find their extensive application as a promising material
      in medicine due to unique characteristics. However, such materials have been
      accompanied with potentially hazardous effects on human health. The toxicity of
      CNTs may vary depending on their structural characteristics, surface properties
      and chemical composition. To gain insight into the toxicity of CNTs in vivo and
      in vitro, we summarize contributing factors for the toxic effects of CNTs in this
      review. In addition, we elaborate on the toxic effects and mechanisms in target
      sites at systemic, organic, cellular, and biomacromolecule levels. Various issues
      are reported to be effected when exposed to CNTs including (1) blood circulation,
      (2) lymph circulation, (3) lung, (4) heart, (5) kidney, (6) spleen, (7) bone
      marrow, and (8) blood brain barrier. Though there have been published reports on
      the toxic effects of CNTs to date, more studies will still be needed to gain full
      understanding of their potential toxicity and underlying mechanisms. 

PMID- 24016108
TI  - The toxicity and pharmacokinetics of carbon nanotubes as an effective drug
      carrier.
AB  - Carbon nanotubes have shown broad potential in biomedical applications, given
      their unique mechanical, optical, and chemical properties. Functionalized carbon
      nanotubes not only can deliver drug into specific organs but also can inherently
      produce heating by near-infrared laser radiation for cancer therapy. However, the
      toxicological and pharmacological profile of such carbon nanotube system will
      have to be determined prior to any clinical study undertaken. For providing a
      guide to develop safe drug carriers, this review discusses the functionalization,
      toxicity and pharmacokinetics of carbon nanotubes. Lastly, the drug delivery and
      thermal ablation on carbon nanotubes are proposed. 

PMID- 24016109
TI  - Pharmacokinetics and applications of magnetic nanoparticles.
AB  - Nanomaterials possess enormous potential for biomedical applications, while some
      of the most promising nanomaterials currently under investigation demonstrate
      prolonged tissue retention and contain heavy metals. This article investigates
      the pharmacokinetics of magnetic nanoparticles (MNPs) to help identify promising
      candidates with optimal pharmacokinetics and clearance from the body for
      biomedical use and synthesize nanomaterials ideal for biomedical use. The term
      'magnetic nanoparticles' (MNPs) refers to nanoparticles with ferromagnetism. Such
      nanoparticles have special characteristics, and many in the field of biological
      field have undertaken research involving, e.g., immobilized enzymes and proteins,
      biological cells, macromolecular separation, drug carriers, and targeted, immune,
      biological sensors. 

PMID- 24016110
TI  - Review of and perspectives on the toxicology of graphene-based materials.
AB  - Graphene possesses a wide range of potential biomedical applications because of
      the unique physical and chemical properties. However, the side effects of
      grapheme and its derivatives on a number of biological models even on human body
      are still not very clear. Therefore, to properly assess the potential risk of
      grapheme and its derivatives, we summarize the current state of academic
      knowledge on their toxicity. 

PMID- 24016111
TI  - Perspectives on the toxicology of cadmium-based quantum dots.
AB  - As the number of applications of quantum dots (QDs) grows, the likelihood of
      exposure increases. Because these metals have the potential for detrimental
      environmental and health effects, concerns have been raised over our lack of
      understanding about the fate of these products. Among various types of QDs,
      cadmium-based quantum dots attract the greatest attention due to their wide
      applications. To properly assess the potential risk of cadmium-containing QDs, we
      summarize the current state of academic knowledge on the toxicity of cadmium
      based QDs. 

PMID- 24016112
TI  - Polymeric nanoparticles for a drug delivery system.
AB  - In recent years, nanotechnology research has made great strides in the area of
      pharmacy, especially for drug delivery systems. Polymeric nanoparticles provide
      significant stability in anti-neoplastic drug research and have demonstrated the
      ability to solve the problems of therapeutic efficacy and diagnostic sensitivity.
      In this review, we describe the specific advantages of polymeric nanoparticles
      and their applications for a drug delivery system. The latest research on PHA
      based polymeric nanoparticles and PLGA is also discussed. 

PMID- 24016113
TI  - An overview of the pharmacokinetics of polymer-based nanoassemblies and
      nanoparticles.
AB  - Advancements in the design and synthesis of polymer-based nanoassemblies and
      nanoparticles, combined with achievements in nanotechnology and medicine, have
      resulted in remarkable applications of polymer nanosystems in the areas of
      nanomedicine and pharmaceutical sciences. However, a complete understanding of
      the absorption, distribution, metabolism, and elimination (ADME) processes of
      such polymer nanosystems in living systems has not been achieved. The influences
      of the pharmacokinetic parameters of polymer nanomaterials on the ADME processes
      are reviewed in this article, with discussions of the absorption and
      transportation of polymer nanoparticles across biological barriers, the factors
      affecting the bodily distribution of polymer nanocarriers, the transformation of
      polymer nanomaterials in vivo, the elimination pathway of polymer nanoparticles
      from biological systems, and perspectives of future pharmacokinetics and safety
      investigations of polymer-based nanoassemblies. A full and better understanding
      of the pharmacokinetic parameters of polymer-based nanomaterials is of vital
      importance in developing polymer nanosystems with optimal pharmacokinetics and
      biological safety for applications in nanomedicine and the pharmaceutical
      industry. 

PMID- 24016114
TI  - An overview on the pharmacokinetics of quantum dots.
AB  - Recent developments in nanotechnology have paved the way for using quantum dots
      (QDs) in nanodiagnostics and nanotherapeutics. Careful design and preparation of
      QDs are guided by these application-specific requirements. QDs will probably be
      one of the first nanomaterial to reach clinical applications, however many
      challenges in this field have yet to be overcome. In this article, we present an
      extensive review of the pharmacokinetic properties of QDs. The representative
      studies responsible for observing quantitative determination of QDs
      biodistribution in vivo are presented. The effects of size, surface chemistry,
      and target moiety on their pharmacokinetics are discussed. Finally, future
      directions for improving the pharmacokinetics of QDs and perspectives in the
      field are discussed. The understanding of its absorption, distribution,
      metabolism, and excretion from the body will provide important guidelines for the
      successful clinical use of QDs. 

PMID- 24016115
TI  - Mechanism-based inhibition of CYP450: an indicator of drug-induced
      hepatotoxicity.
AB  - Xenobiotics are converted by cytochrome P450 (CYP450) into highly reactive
      metabolites (RMs) that covalently bind to the catalytic site of the enzyme
      itself, subsequently causing mechanism-based inhibition. This phenomenon is one
      of the fates of RMs in the liver. Depending on their affinity to nucleophiles
      (high-electron density compounds), RMs also may act as hepatotoxic agents by
      binding to intracellular macromolecules. The present study summarized 29
      mechanism-based inhibitors (drugs) with clinical hepatotoxicity. Eighteen of
      these drugs cause hepatotoxicity (7 through idiosyncratic drug-induced liver
      injury) via their RMs. The liver injury caused by remaining 11 drugs, namely,
      fluoxetine, verapamil, furan-containing compounds, and human immunodeficiency
      virus protease inhibitors, cannot be excluded via RMs because of limited data. A
      regular pattern for RM-induced hepatotoxicity is summarized: (a) formation of RM
      protein adducts that trigger immune responses; (b) covalent binding of RMs to
      intracellular macromolecules (mitochondria is a commonly victim) may lead to
      reactive oxygen species (ROS) overproduction, respiratory chain dysfunction, cell
      stress, and so on; and (c) RM overproduction, which results in glutathione (GSH)
      depletion. The binding mechanism of RMs to CYP450s and the quantitative
      parameters (KI, Kinact, and Kinact/KI) of the mechanism-based inhibitors of
      CYP450s are weakly correlated with the occurrence of hepatotoxicity, while the
      induction of CYP450 expression (11/29 drugs) may contribute to hepatotoxicity via
      excessive ROS and RM generation. These results suggest that mechanism-based
      inhibition is an indicator of RM formation and may thus be used to identify drugs
      with RM-induced hepatotoxic potential (particularly idiosyncratic drug-induced
      liver injury). 

PMID- 24016116
TI  - Color-blind racial ideology: theory, training, and measurement implications in
      psychology.
AB  - Synthesizing the interdisciplinary literature, we characterize color-blind racial
      ideology (CBRI) as consisting of two interrelated domains: color-evasion (i.e.,
      denial of racial differences by emphasizing sameness) and power-evasion (i.e.,
      denial of racism by emphasizing equal opportunities). Mounting empirical data
      suggest that the color-evasion dimension is ineffective and in fact promotes
      interracial tension and potential inequality. CBRI may be conceived as an
      ultramodern or contemporary form of racism and a legitimizing ideology used to
      justify the racial status quo. Four types of CBRI are described: denial of (a)
      race, (b) blatant racial issues, (c) institutional racism, and (d) White
      privilege. We discuss empirical findings suggesting a relationship between CBRI
      and increased racial prejudice, racial anger, and racial fear. Implications for
      education, training, and research are provided.

PMID- 24016117
TI  - George A. Miller (1920-2012).
AB  - Presents an obituary for George A. Miller (1920-2012). Miller ranks among the
      most important psychologists of the 20th century. In addition to writing one of
      the best known papers in the history of psychology ("The Magical Number Seven,
      Plus or Minus Two: Some Limits on Our Capacity for Processing Information,"
      published in Psychological Review in 1956), Miller also fomented the cognitive
      revolution, invented psycholinguistics and cognitive psychology, imported
      powerful ideas from the theories of information, communication, grammar,
      semantics, and artificial intelligence, and left us a sparkling oeuvre that
      proves that a rigorous scientist needn't write in soggy prose. Honors rained down
      on Miller. APA gave him the Award for Distinguished Scientific Contributions
      (1963), the American Psychological Foundation Gold Medal Award for Life
      Achievement in Psychological Science (1990), the William James Book Award (1992,
      for The Science of Words), and the Award for Lifetime Contributions to Psychology
      (2003), and named a prize after him, as did the Cognitive Neuroscience Society.
      Miller was also honored by the Association for Psychological Science and the
      American Speech and Hearing Association. In 2000, he won the John P. McGovern
      Award in the Behavioral Sciences from the American Association for the
      Advancement of Science, and in 1991, the National Medal of Science, the country's
      highest scientific honor.

PMID- 24016118
TI  - David L. Rosenhan (1929-2012).
AB  - Presents an obituary for David L. Rosenhan (1929-2012). A distinguished
      psychologist and professor emeritus at Stanford University, Rosenhan died
      February 6, 2012, at the age of 82, after a long illness. Born in Jersey City,
      New Jersey, on November 22, 1929, he received a bachelor's degree in mathematics
      (1951) from Yeshiva College and a master's degree in economics (1953) and a
      doctorate in psychology (1958) from Columbia University. A professor of law and
      of psychology at Stanford University from 1971 until his retirement in 1998,
      Rosenhan was a pioneer in applying psychological methods to the practice of law,
      including the examination of expert witnesses, jury selection, and jury
      deliberation. A former president of the American Psychology-Law Society and of
      the American Board of Forensic Psychology, Rosenhan was a fellow of the American
      Association for the Advancement of Science, of the American Psychological
      Association, and of the American Psychological Society. Before joining the
      Stanford Law School faculty, he was a member of the faculties of Swarthmore
      College, Princeton University, Haverford College, and the University of
      Pennsylvania. He also served as a research psychologist at the Educational
      Testing Service. As generations of Stanford students can attest, David Rosenhan
      was a spellbinding lecturer who managed to convey the sense that he was speaking
      to each individual, no matter how large the group. To his graduate students, he
      was consistently encouraging and optimistic, always ready to share a joke or
      story, and gently encouraging of their creativity and progressive independence as
      researchers. The lessons he cared most about offering, in the classroom as in his
      research, were about human dignity and the need to confront abuse of power and
      human frailties.

PMID- 24016119
TI  - Robert (Bob) L. Helmreich (1937-2012).
AB  - Presents an obituary for Robert (Bob) L. Helmreich (1937-2012). Helmreich was
      born April 29, 1937, in Kansas City, Missouri, the only son of Ralph and Caroline
      Helmreich. Bob received his undergraduate degree from Yale University in 1959. He
      immediately enlisted in the U.S. Navy, where he served for four years. Upon his
      retirement from the service he was executive officer of the USS Decatur (DD-936).
      Perhaps it was his service in the Navy that sparked his lifelong professional
      interest in how people work together in teams to accomplish technically precise
      goals. He returned to Yale University to obtain a doctor of philosophy degree in
      social psychology under Barry Collins. Bob joined the faculty at The University
      of Texas at Austin as an assistant professor in 1966 and remained on the faculty
      in the Department of Psychology until his retirement in 2007, 41 years later.
      During the course of his career, Helmreich published more than 200 research
      articles and monographs. Most of his publications dealt with issues related to
      airline and medical safety, and much of this work was done in collaboration with
      graduate students and colleagues. In recognition of his extensive contributions
      to improving crew performance, in 2005 Helmreich received the Lifetime
      Achievement Award from the Flight Safety Foundation. Helmreich also received the
      Franklin V. Taylor Award for Outstanding Contributions in the Field of Applied
      Experimental/Engineering Psychology from the American Psychological Association
      (APA), the Pro Bene Meritus A ward from The University of Texas (for his
      commitment to the liberal arts), and the David S. Sheridan Award from Albany
      Medical College.

PMID- 24016120
TI  - Robert M. Guion (1924-2012).
AB  - Presents an obituary for Robert M. Guion (1924-2012). Bob received his bachelor's
      degree from the University of Iowa in 1948 and his master's degree (1950) and
      doctorate (1952) from Purdue University, the latter in I-O psychology. His
      doctoral mentor, about whom he always spoke with gratitude, was C. H. Lawshe.
      Although Bob found employment opportunities limited on graduation, he knew that
      he wanted the freedom and independence of an academic position. He joined the
      faculty at Bowling Green State University (BGSU) in 1952. Bob served as chair of
      the department from 1966 to 1971 and edited the Journal of Applied Psychology
      from 1983 to 1988. He continued to rise through the professorial ranks and was
      ultimately named a Distinguished University Professor. In 1965, Bob won the James
      McKeen Cattell Award for research design from Division 14 (Society for Industrial
      and Organizational Psychology; SIOP) of the American Psychological Association
      (APA). He won it again in 1981. His landmark text Personnel Testing (1965, McGraw
      Hill) was required reading for almost every I-O graduate student. In 1998 he
      published another classic, Assessment, Measurement, and Prediction for Personnel
      Decisions (Erlbaum). As an educator, Bob led the development of the master's and
      doctoral programs at BGSU and served as mentor for many of today's leaders in the
      field. As a contributor to professional psychology, he served as the president of
      two APA divisions, 14 and 5 (Evaluation, Measurement and Statistics), and also
      chaired APA's Board of Scientific Affairs. His career is a model of the blend of
      theory, research, and application. Bob was a model of integrity and deeply
      believed that the waste of human resources should pain the professional
      conscience of I-O psychologists. Bob worked tirelessly toward the development of
      a fundamental science that promotes human welfare at work.

PMID- 24016121
TI  - Mollie Stevens Smart (1916-2012).
AB  - Presents an obituary for Mollie Stevens Smart (1916-2012). Mollie attended the
      University of Toronto, from which she graduated with honors in psychology at age
      20 in 1936. She studied and worked at the Merrill-Palmer Institute in Detroit,
      earning a master's degree in child development from the University of Michigan in
      1941. She earned her doctorate in educational psychology at the University of
      Delhi in 1969. An author, teacher, and mentor, Mollie won Fulbright research
      grants to India and New Zealand and lectured in the United States, India, New
      Zealand, Canada, and China. She wrote 26 books, most co-authored with her
      husband, Russell (Rus) C. Smart. Beginning in the 1940s, when Freudian theory had
      a strong grip on the popular view of child development, the books placed the
      developing child in the context of family and community systems. The Smarts' best
      selling college textbook Children: Development and Relationships (1967, 1973,
      1977, 1982) was based on the theories of Erik Erikson and Jean Piaget. Mollie was
      a member of the American Psychological Association throughout her professional
      career and held memberships also in the Society for Research in Child
      Development, the National Council on Family Relations, the Groves Conference on
      Marriage and Family, and the Fulbright Association. After moving to Ridgefield,
      Washington, in 2003 with her daughter Ellen following Rus's death in 1996, she
      applied her great knowledge to advise a community-based organization that serves
      the needs of new babies born into destitute families. Mollie died at home in
      Ridgefield on October 22, 2012, at age 96.

PMID- 24016122
TI  - Robert Spurlin Waldrop (1912-2012).
AB  - Presents an obituary for Robert Spurlin Waldrop (1912-2012). After receiving a
      bachelor of arts degree at the University of Oklahoma in 1934 with a major in
      philosophy and a minor in psychology, Waldrop received a bachelor of divinity
      degree from the McCormick Theological Seminary in Chicago in 1937. He began
      graduate work in psychology at the University of Chicago (1937-1940), where he
      worked with L. L. Thurstone and became interested in the work of William Sheldon.
      He continued graduate work at the University of Michigan (1940-1943) until he was
      inducted into the U.S. Navy during World War II. After his discharge from the
      Navy in 1946, Waldrop returned to Ann Arbor to resume his doctoral studies and
      was additionally appointed director of the Veterans Service Bureau at the
      University of Michigan. He completed his doctorate in June 1948 and in the fall
      accepted a position as dean of students at Vanderbilt University. Waldrop's work
      with veterans and development of doctoral counseling psychology brought him to
      the attention of the Department of Veterans Affairs. Waldrop played a pivotal
      role in the VA's decision to establish doctoral-level counseling psychologists in
      VA hospitals. He resigned from the VA in 1961 to return to academic life. He
      accepted a position as professor of psychology in the Department of Psychology at
      the University of Maryland, College Park, from which he retired in 1979.
      Throughout his career, Waldrop was involved in both professional and community
      affairs. Waldrop lived the history of modern psychology and contributed to that
      history.

PMID- 24016125
TI  - Social justice and the politics of recognition.
AB  - Comments on the original article, "Psychology and social justice: Why we do what
      we do" by M. J. T. Vasquez (see record 2012-18676-002). Vasquez pointed to
      numerous initiatives and task forces that the American Psychological Association
      (APA) has established to address the marginalization and subordination of various
      groups. There is little doubt that the concerns addressed by these initiatives
      and task forces are important and play a central role in the development of a
      just society. Although Vasquez noted that "social realities are important
      determinants of distress" she failed to appreciate the extent to which our social
      relations emerge against the background of specific political and economic
      structures. The cost of this oversight is the perpetuation of a politics of
      recognition that does little to address the economic inequalities that are a
      defining feature of unjust societies. Were APA to restrict its attention to
      psychological distress or access to resources, it would place APA in the service
      of maintaining rather than transforming the existing structure of society. APA
      should consider developing initiatives and task forces to investigate the role
      that capitalism plays in the perpetuation of inequality and exploitation. It may
      also be time to reflect on why an institution that claims to be dedicated to
      social justice has had so little to say about one of the dominant features of
      modern society.

PMID- 24016126
TI  - Evidence-based interventions need to be more systematic, not more disruptive.
AB  - Comments on the original article, "Disruptive innovations for designing and
      diffusing evidence-based interventions," by M. J. Rotheram-Borus et al. (see
      record 2012-10813-001). We concur that psychology has become over
      compartmentalized and that research and interventions alike fail to reflect the
      full complexity of people's lives. More person-centered and family-centered
      approaches are needed, not only for intervention but also for prevention and
      research. As Rotheram-Borus et al. suggested, expanding delivery vehicles is one
      important way forward. Unfortunately, however, our knowledge about what should be
      delivered by these vehicles is regrettably limited. Psychological interventions
      are too often developed, evaluated, and disseminated as fully formed entities. As
      a result, one cannot identify the source of the positive effects when they occur.
      This creates a problem for Rotheram-Borus and colleagues' suggestion that new
      interventions could be created by synthesizing information across randomized
      controlled trials and including the most common elements. "Common" is not
      equivalent to "robust" or "effective," as illustrated by the historical use of
      leeches as a common biomedical intervention for a host of ailments. In cases
      where curricula with common elements have demonstrated positive effects, the
      research does not indicate which elements produce change and which may have no or
      even iatrogenic effects (as has been found in more than one violence prevention
      program).

PMID- 24016127
TI  - Iterative quality improvement can occur faster than one element at a time.
AB  - Responds to the comments by S. Hamby and J. Grych (see record 2013-31242-011) on
      the current authors' original article, "Disruptive innovations for designing and
      diffusing evidence-based interventions" (see record 2012-10813-001). Hamby and
      Grych implied that the careful and systematic testing of one element at a time is
      a prerequisite to its application in service contexts. This is certainly one
      valid approach to generating such evidence and follows the dominant paradigm of
      current scientific norms. In fact, it would partially contribute to a more
      molecular and theory-based understanding of intervention efficacy than we
      currently have; however, we believe that the choice to apply elements of an
      intervention or to study them first is a false dichotomy given the real-world
      complexities of behavioral interventions, ongoing need for interventions to
      impact families currently in need, and funding environments.

PMID- 24016128
TI  - How big is the competent community? And who gets in?
AB  - Comments on the original article, "The competent community: Toward a vital
      reformulation of professional ethics," by W. B. Johnson et al. (see record 2012
      04007-001). Johnson et al. offered a welcome and promising glimpse into the
      future of psychology ethics. The notion that the field of psychology should
      encourage its members to make a communitarian commitment toward caring for each
      other as well as those we serve seems indubitable and perhaps even overdue.
      Assuming that the merits of the "competent community" are recognized, a couple of
      subsequent questions regarding its implementation should be addressed. First, how
      big should the competent community be? The second question centers on who gets in
      to our professional community in the first place: Should admission to graduate
      programs in psychology depend on an applicant's commitment to communitarianism?

PMID- 24016129
TI  - Infusing psychology ethics with a communitarian approach.
AB  - Responds to the comments by A. M. Pomerantz (see record 2013-31242-013) on the
      current authors' original article, "The competent community: Toward a vital
      reformulation of professional ethics" (see record 2012-04007-001). Here, the
      current authors address Pomerantz's two main questions regarding the size of and
      admission to competent communities in professional psychology.

PMID- 24016130
TI  - Does nasal echolocation influence the modularity of the mammal skull?
AB  - In vertebrates, changes in cranial modularity can evolve rapidly in response to
      selection. However, mammals have apparently maintained their pattern of cranial
      integration throughout their evolutionary history and across tremendous
      morphological and ecological diversity. Here, we use phylogenetic, geometric
      morphometric and comparative analyses to test the hypothesis that the modularity
      of the mammalian skull has been remodelled in rhinolophid bats due to the novel
      and critical function of the nasal cavity in echolocation. We predicted that
      nasal echolocation has resulted in the evolution of a third cranial module, the
      'nasal dome', in addition to the braincase and rostrum modules, which are
      conserved across mammals. We also test for similarities in the evolution of skull
      shape in relation to habitat across rhinolophids. We find that, despite broad
      variation in the shape of the nasal dome, the integration of the rhinolophid
      skull is highly consistent with conserved patterns of modularity found in other
      mammals. Across their broad geographical distribution, cranial shape in
      rhinolophids follows two major divisions that could reflect adaptations to
      dietary and environmental differences in African versus South Asian
      distributions. Our results highlight the potential of a relatively simple modular
      template to generate broad morphological and functional variation in mammals. 

PMID- 24016131
TI  - The robust reliability of neuropsychological measures: meta-analyses of test
      retest correlations.
AB  - Test-retest reliability is an important psychometric property relevant to
      assessment instruments typically used in neuropsychological assessment. This
      review presents a quantitative summary of test-retest reliability coefficients
      for a variety of widely used neuropsychological measures. In general, the meta
      analytic test-retest reliabilities of the test scores ranged from adequate to
      high (i.e., r=.7 and higher). Furthermore, the reliability values were largely
      robust across factors such as age, clinical diagnosis, and the use of alternate
      forms. The values for some of the memory and executive functioning scores were
      lower (i.e., less than r=.7). Some of the possible reasons for these lower values
      include ceiling effects, practice effects, and across time variability in
      cognitive abilities measured by those tests. In general, neuropsychologists who
      use these measures in their assessments can be encouraged by the magnitude of the
      majority of the meta-analytic test-retest correlations obtained. 

PMID- 24016133
TI  - Ethanol or bioelectricity? Life cycle assessment of lignocellulosic bioenergy use
      in light-duty vehicles.
AB  - Our study evaluates life cycle energy use and GHG emissions of lignocellulosic
      ethanol and bioelectricity use in U.S. light-duty vehicles. The well-to-pump,
      pump-to-wheel, and vehicle cycle stages are modeled. All ethanol (E85) and
      bioelectricity pathways have similar life cycle fossil energy use (~ 100 MJ/100
      vehicle kilometers traveled (VKT)) and net GHG emissions (~5 kg CO2eq./100 VKT),
      considerably lower (65-85%) than those of reference gasoline and U.S. grid
      electricity pathways. E85 use in a hybrid vehicle and bioelectricity use in a
      fully electric vehicle also have similar life cycle biomass and total energy use
      (~ 350 and ~450 MJ/100 VKT, respectively); differences in well-to-pump and pump
      to-wheel efficiencies can largely offset each other. Our energy use and net GHG
      emissions results contrast with findings in literature, which report better
      performance on these metrics for bioelectricity compared to ethanol. The primary
      source of differences in the studies is related to our development of pathways
      with comparable vehicle characteristics. Ethanol or vehicle electrification can
      reduce petroleum use, while bioelectricity may displace nonpetroleum energy
      sources. Regional characteristics may create conditions under which either
      ethanol or bioelectricity may be the superior option; however, neither has a
      clear advantage in terms of GHG emissions or energy use.

PMID- 24016134
TI  - Direct care staff perspectives related to physical activity in mental health
      group homes.
AB  - Sedentary lifestyle is a modifiable risk factor that contributes to health
      disparities in individuals with serious mental illness. Direct care staff in
      mental health group homes were surveyed to determine barriers and resource needs
      related to conducting physical activity interventions with individuals. An
      investigator-designed survey was used. The most significant barriers cited by
      staff were individuals did not want to engage in physical activity and staff
      needed more information about how to conduct physical activity interventions.
      Resource needs cited by staff included engagement strategies to gain and maintain
      individual interest as well as resource acquisition. Direct care staff are well
      positioned to deliver physical activity interventions but need support and
      direction to engage individuals in safe and effective exercise. Mental health
      nurses are well placed to provide support and direction to staff for these
      interventions.

PMID- 24016136
TI  - Silver-gold alloy nanoclusters as a fluorescence-enhanced probe for aluminum ion
      sensing.
AB  - In this paper, the development of a simple method is described for preparing
      highly red fluorescent mercaptosuccinic acid stabilized AgAu alloy nanoclusters
      (MSA-AgAu NCs) through the core etching of Ag nanoparticles (NPs) and a galvanic
      exchange reaction using nonorganic solvent and no multistep centrifuge washing.
      The as-prepared MSA-AgAu NCs were characterized using spectroscopic and
      microscopic techniques. After covalently attaching methoxy-poly(ethylene glycol)
      NH2 (m-PEG-NH2), PEGylated MSA-AgAu NCs were still stable even in 1 M NaCl.
      Probably based on the deposition of Al(3+)-enhanced fluorescence, the PEGylated
      MSA-AgAu NCs offered highly selective and sensitive sensing of Al(3+) in aqueous
      solution with a detection limit of 0.8 MUM. 

PMID- 24016137
TI  - Clostridium perfringens septicaemia.

PMID- 24016135
TI  - Trouble brewing: pregaming among high school and incoming college students.
AB  - Pregaming (a.k.a., "prepartying," "pre-funking," or "predrinking") consists of
      drinking before going to a social function or gathering where alcohol may or may
      not be served. Existing research suggests that pregaming in high school and pre
      college (i.e., the period between high school graduation and the start of
      college) is widespread. Moreover, pregaming prevalence appears to rapidly
      increase after students graduate from high school and transition into college.
      Thus, the purpose of this brief review is threefold: (a) to summarize the
      existing (albeit limited) research on pregaming among high school students and
      incoming college freshmen, (b) to present an overview of the risk factors that
      have been identified for participation in pregaming, and (c) to discuss the
      implications for practice that may be particularly relevant for school
      employed/affiliated nurses as well as health practitioners who work in college
      settings.

PMID- 24016138
TI  - Perceptual fluency, auditory generation, and metamemory: analyzing the perceptual
      fluency hypothesis in the auditory modality.
AB  - Judgments of learning (JOLs) are sometimes influenced by factors that do not
      impact actual memory performance. One recent proposal is that perceptual fluency
      during encoding affects metamemory and is a basis of metacognitive illusions. In
      the present experiments, participants identified aurally presented words that
      contained inter-spliced silences (the generate condition) or that were intact, a
      manipulation analogous to visual generation manipulations. The generate condition
      produced lower perceptual fluency as assessed by both accuracy and identification
      latency. Consistent with the perceptual fluency hypothesis, the less fluent,
      generate condition produced lower JOLs than the intact condition. However, actual
      memory performance was greater in the generation than intact condition in free
      recall (Experiment 1) and recognition (Experiment 3). The negative effect of
      generation on JOLs occurred for both aggregate and item-by-item JOLs, but in the
      latter case, the positive generation effect in actual memory performance was
      reduced or eliminated (as also occurs with visual generation tasks; Experiments 2
      and 4). Furthermore, the decrease in perceptual fluency produced by the
      generation manipulation was correlated with the decrease in JOLs for this
      condition (Experiment 5). The negative effect of generation on JOLs persisted
      even when participants were warned that the generation condition produces equal
      or greater memory performance compared to the intact condition (Experiment 6).
      The results are in accord with the perceptual fluency hypothesis and show that
      this metamemory illusion is related to objective measures of perceptual
      difficulty. With regard to actual memory performance, this novel auditory
      generation manipulation produces results consistent with those produced in the
      visual modality.

PMID- 24016139
TI  - Collaborative encoding and memory accuracy: examining the effects of interactive
      components of co-construction processes.
AB  - In 2 experiments, the effect of collaborative encoding on memory was examined by
      testing 2 interactive components of co-construction processes. One component
      focused on the nature of the interactive exchange between collaborators: As the
      partners worked together to create descriptions about ways to interact with
      familiar objects, constraints were imposed on the interactions by requiring them
      to take turns (Experiment 1) or to interact without constraints (Experiment 2).
      The nature of the relationship between partners was manipulated as well by
      including 2 pair types, friends or unfamiliar peers (Experiments 1 and 2).
      Interactive component effects were found to influence spontaneous activations
      through content analyses of participants' descriptions, the patterns of false
      recognition errors, and the relationship between content and errors. The findings
      highlight the value of examining the content of participants' collaborative
      efforts when assessing the effects of collaborative encoding on memory and point
      to mechanisms mediating collaboration's effects. Because the interactions
      occurred within the context of an imagery generation task, the findings are also
      intriguing because of their implications for the use of guided imagery techniques
      that incorporate co-construction processes.

PMID- 24016140
TI  - Think twice and then: combining or choosing in dialectical bootstrapping?
AB  - Individuals can partly recreate the "wisdom of crowds" within their own minds by
      combining nonredundant estimates they themselves have generated. Herzog and
      Hertwig (2009) showed that this accuracy gain could be boosted by urging people
      to actively think differently when generating a 2nd estimate ("dialectical
      bootstrapping"). Although the "crowd within" promises accuracy gains, it remains
      unclear whether and when people spontaneously reap those gains. What makes people
      combine their estimates rather than trying to identify the better one? This
      research found that participants were more likely to combine when they were
      instructed to actively contradict themselves. Furthermore, they were more likely
      to combine as the size of the disagreement between 1st and 2nd estimate grew.
      People thus acted as if they were hedging against the risk of making large
      errors. Finally, when people pursued a strategy other than combination, they were
      not able to outperform their crowd within.

PMID- 24016141
TI  - A forgotten aspect of the NICE reference case: an observational study of the
      health related quality of life impact on caregivers of people with multiple
      sclerosis.
AB  - BACKGROUND: There are few published health technology assessments that have
      included the impact of a disease or treatment on caregivers' health related
      quality of life (HRQL). The objectives of this study were to explore the overall
      HRQL of caregivers of people with Multiple Sclerosis compared to matched
      controls, and more specifically explore the impact of different levels of
      functioning in people with MS on caregivers' HRQL scores. METHODS: A cross
      sectional observational study conducted as an online survey was undertaken in the
      UK. 200 caregivers of people with MS and 200 matched controls completed the EQ
      5D, SF-36, HADS and a socio-demographic questionnaire. Caregivers also completed
      the Patient Determined Disease Steps questionnaire as a measure of MS severity.
      Differences in HRQL between caregivers and controls were assessed using t-tests
      and chi square analyses as appropriate. Ordinary Least Squares regression was
      also used to evaluate the disutility of being a caregiver compared to controls
      stratified by MS severity. RESULTS: Caregivers reported significantly lower HRQL,
      as measured by the SF-36, HADS and EQ-5D, compared to matched controls. A lower
      level of functioning in people with MS was mirrored by lower levels of
      caregivers' HRQL. At the point at which mobility problems required wheelchair use
      caregivers reported better HRQL. CONCLUSIONS: The potential impact of caregiving
      on HRQL is an important consideration for economic evaluations. In relation to
      MS, the results suggest that caregiver's HRQL deteriorates as the people with MS
      lose functioning; thus treatments that delay loss of function may have a benefit
      for caregivers as well as patients.

PMID- 24016142
TI  - Electrical modulation of the local conduction at oxide tubular interfaces.
AB  - Heterointerfaces between complex oxides have sparked considerable interest due to
      their fascinating physical properties and their offering of new possibilities for
      next-generation electronic devices. The key to realize practical applications is
      the control through external stimuli. In this study, we take the self-assembled
      BiFeO3-CoFe2O4 tubular interface as a model system to demonstrate the nonvolatile
      electric control of the local conduction at the complex oxide tubular interface.
      The fundamental mechanism behind this modulation was explored based on static and
      dynamic conductive atomic force microscopies. We found the movement of oxygen
      vacancies in the BiFeO3-CoFe2O4 heterostructure is the key to drive this
      intriguing behavior. This study delivers a possibility in developing next
      generation electronic devices. 

PMID- 24016144
TI  - One-pot, two-step synthesis of imidazo[1,2-a]benzimidazoles via a multicomponent
      [4 + 1] cycloaddition reaction.
AB  - A one-pot, two-step synthesis of imidazo[1,2-a]benzimidazoles has been achieved
      by a three-component reaction of 2-aminobenzimidazoles with an aromatic aldehyde
      and an isocyanide. The reaction involving condensation of 2-aminobenzimidazole
      with an aldehyde is run under microwave activation to generate an imine
      intermediate under basic conditions which then undergoes [4 + 1] cycloaddition
      with an isocyanide. 

PMID- 24016143
TI  - STI in remote communities: improved and enhanced primary health care (STRIVE)
      study protocol: a cluster randomised controlled trial comparing 'usual practice'
      STI care to enhanced care in remote primary health care services in Australia.
AB  - BACKGROUND: Despite two decades of interventions, rates of sexually transmissible
      infections (STI) in remote Australian Aboriginal communities remain unacceptably
      high. Routine notifications data from 2011 indicate rates of chlamydia and
      gonorrhoea among Aboriginal people in remote settings were 8 and 61 times higher
      respectively than in the non-Indigenous population. METHODS/DESIGN: STRIVE is a
      stepped-wedge cluster randomised trial designed to compare a sexual health
      quality improvement program (SHQIP) to usual STI clinical care delivered in
      remote primary health care services. The SHQIP is a multifaceted intervention
      comprising annual assessments of sexual health service delivery, implementation
      of a sexual health action plan, six-monthly clinical service activity data
      reports, regular feedback meetings with a regional coordinator, training and
      financial incentive payments. The trial clusters comprise either a single
      community or several communities grouped together based on geographic proximity
      and cultural ties. The primary outcomes are: prevalence of chlamydia, gonorrhoea
      and trichomonas in Aboriginal residents aged 16-34 years, and performance in
      clinical management of STIs based on best practice indicators. STRIVE will be
      conducted over five years comprising one and a half years of trial initiation and
      community consultation, three years of trial conditions, and a half year of data
      analysis. The trial was initiated in 68 remote Aboriginal health services in the
      Northern Territory, Queensland and Western Australia. DISCUSSION: STRIVE is the
      first cluster randomised trial in STI care in remote Aboriginal health services.
      The trial will provide evidence to inform future culturally appropriate STI
      clinical care and control strategies in communities with high STI rates. TRIAL
      REGISTRATION: Australian and New Zealand Clinical Trials Registry
      ACTRN12610000358044.

PMID- 24016145
TI  - In situ degradability and selected ruminal constituents of sheep fed with peanut
      forage hay.
AB  - Because legumes are a very important feed source for ruminants, the aim of this
      study was to evaluate the ideal inclusion level of hay Arachis pintoi cv.
      Belmonte in sheep diets by measuring the dry matter intake (DMI), concentration
      of volatile fatty acids, ammonia-nitrogen concentration, ruminal pH and the in
      situ degradability of dry matter (DM) and crude protein (CP). In the experiment
      with four sheep, a 4 * 4 Latin Square design was used with four periods and four
      treatments (0%, 30%, 60% and 100% Arachis replacing grass hay). Significant
      interactions were observed between treatments and sampling times for ammonia
      nitrogen and acetate, propionate and butyrate concentration and the
      acetate:propionate ratio. The ruminal pH and total volatile fatty acids
      concentration were not affected by interaction between treatments and sampling
      time. The degradation of DM and CP was similar, rising with the increasing
      content of Arachis, showing a linear effect. The treatment containing 60% of
      Arachis showed best results, with good levels of daily weight gain and higher
      ruminal concentrations of volatile fatty acids. The legume showed high levels of
      CP, high digestibility and appropriate levels of fibre, with excellent standards
      of degradation and ruminal characteristics. The use of the legume  Arachis for
      ruminants is a promising option of nutrient supply to meet production demands of
      these animals. 

PMID- 24016146
TI  - Systemic and local expression levels of TNF-like ligand 1A and its decoy receptor
      3 are increased in primary biliary cirrhosis.
AB  - BACKGROUND & AIMS: Through a genome-wide association study of a Japanese
      population, we recently identified TNFSF15, a gene encoding TNF-like ligand 1A
      (TL1A), as a susceptibility gene for primary biliary cirrhosis (PBC). We
      investigated the clinical significance of TL1A and one of its receptors, decoy
      receptor 3 (DcR3), in PBC. METHODS: We analysed the systemic and local expression
      of TL1A and DcR3 in 110 PBC patients and 46 healthy controls using enzyme-linked
      immunosorbent assay, quantitative polymerase chain reaction and
      immunohistochemical staining. RESULTS: Serum TL1A levels were significantly
      increased in PBC patients at both early and late stages as compared with healthy
      controls, and its levels were significantly decreased in early-stage PBC patients
      after ursodeoxycholic acid (UDCA) treatment. TL1A was immunohistochemically
      localized to biliary epithelial cells, Kupffer cells, blood vessels and
      infiltrating mononuclear cells in the PBC liver. In addition, TL1A messenger RNA
      expression was increased in the PBC liver as compared with the non-diseased
      liver. Serum DcR3 levels were also significantly increased in PBC patients, and
      were significantly decreased after UDCA treatment in early-stage PBC patients.
      CONCLUSIONS: These results indicate that TL1A and DcR3 may play an important role
      in the pathogenesis of PBC.

PMID- 24016147
TI  - Catheter versus surgical ablation of atrial fibrillation after a failed initial
      pulmonary vein isolation procedure: a randomized controlled trial.
AB  - INTRODUCTION: The aim of this prospective randomized study was to compare the
      efficacy and safety of catheter ablation (CA) versus surgical ablation (SA) in
      the treatment of paroxysmal and persistent AF after failed initial pulmonary vein
      isolation procedure. METHODS AND RESULTS: Patients with a history of symptomatic
      AF after a previous failed first ablation procedure were eligible for this study.
      Patients were randomized to CA (n = 32) or SA (n = 32) redo ablation. The primary
      endpoint was recurrence of atrial tachyarrhythmia at 1 year of follow-up. At the
      12-month follow-up, 26 (81%) of the 32 SA group patients and 15 (47%) of the 32
      CA group were AF/AT-free on no antiarrhythmic drugs (P = 0.004, log-rank test).
      In patients with PAF, 17 (85%) patients of the 20 in SA group and 10 (56%)
      patients of the 18 in CA group were AF-free (P = 0.04, log-rank test). In
      patients with PersAF, 9 (75%) patients of the 12 in SA group and 5 (36%) patients
      of the 14 in CA group were AF-free (P = 0.04, log-rank test). The number of the
      serious adverse event in the SA group was significantly higher (1 CA group vs 7
      SA group; P = 0.02). CONCLUSION: In patients with PAF and PersAF after failed
      initial CA, SA is superior to CA for maintenance of sinus rhythm, although
      serious adverse event rate is significantly higher for SA.

PMID- 24016148
TI  - Two-dimensional transition metal honeycomb realized: Hf on Ir(111).
AB  - Two-dimensional (2D) honeycomb systems made of elements with d electrons are
      rare. Here, we report the fabrication of a transition metal (TM) 2D layer,
      namely, hafnium crystalline layers on Ir(111). Experimental characterization
      reveals that the Hf layer has its own honeycomb lattice, morphologically
      identical to graphene. First-principles calculations provide evidence for
      directional bonding between adjacent Hf atoms, analogous to carbon atoms in
      graphene. Calculations further suggest that the freestanding Hf honeycomb could
      be ferromagnetic with magnetic moment MU/Hf = 1.46 MU(B). The realization and
      investigation of TM honeycomb layers extend the scope of 2D structures and could
      bring about novel properties for technological applications.

PMID- 24016149
TI  - Determinants of implementation of maternal health guidelines in Kosovo: mixed
      methods study.
AB  - BACKGROUND: One of the challenges to implementing clinical practice guidelines is
      the need to adapt guidelines to the local context and identify barriers to their
      uptake. Several models of framework are available to consider for use in
      guideline adaptation. METHODS: We completed a multiphase study to explore the
      implementation of maternal health guidelines in Kosovo, focusing on determinants
      of uptake and methods to contextualize for local use. The study involved a
      survey, individual interviews, focus groups, and a consensus meeting with
      relevant stakeholders, including clinicians (obstetricians, midwives), managers,
      researchers, and policy makers from the national Ministry of Health and the World
      Health Organization office in Pristina, Kosovo. RESULTS: Participants identified
      several important barriers to implementation. First, lack of communication
      between clinicians and ministry representatives was seen as leading to
      duplication of effort in creating or adapting guidelines, as well as substantial
      mistrust between clinicians and policy makers. Second, there was a lack of
      communication across clinical groups that provide obstetric care and a lack of
      integration across the entire healthcare system, including rural and urban
      centers. This fragmentation was thought to have directly resulted from the war in
      1998 - 1999. Third, the conflict substantially and adversely affected the
      healthcare infrastructure in Kosovo, which has resulted in an inability to
      monitor quality of care across the country. Furthermore, the impact on
      infrastructure has affected the ability to access required medications
      consistently and to smoothly transfer patients from rural to urban centers.
      Another issue raised during this project was the appropriateness of including
      guideline recommendations perceived to be 'aspirational'. CONCLUSIONS:
      Implementing clinical practice guidelines in low- and middle-income countries
      (LMICs) requires consideration of several specific barriers. Particularly
      pertinent to this study were the effects of recent conflict and the resulting
      fragmentation of healthcare and communication strategies among relevant
      stakeholders. However, as Kosovo rebuilds and invests in infrastructure after the
      conflict, there is a tremendous opportunity to create comprehensive, thoughtful
      strategies to monitor and improve quality of care. To avoid duplication of
      effort, it may be beneficial for LMICs to share information on assessing barriers
      as well as on guideline implementation strategies.

PMID- 24016150
TI  - Do ketoanalogues still have a role in delaying dialysis initiation in CKD
      predialysis patients?
AB  - Early versus later start of dialysis is still a matter of debate. Low-protein
      diets have been used for many decades to delay dialysis initiation. Protein
      restricted diets (0.3-0.6 g protein/kg/day) supplemented with essential amino
      acids and ketoanalogues (sVLPD) can be offered, in association with
      pharmacological treatment, to motivated stage 4-5 chronic kidney disease (CKD)
      patients not having severe comorbid conditions; they probably represent 30-40% of
      the concerned population. A satisfactory adherence to such dietary prescription
      is observed in approximately 50% of the patients. While the results of the
      studies on the effects of this diet on the rate of progression of renal failure
      remain inconclusive, they are highly significant when initiation of dialysis is
      the primary outcome. The correction of uremic symptoms allows for initiation of
      dialysis treatment at a level of residual renal function lower than that usually
      recommended. Most of the CKD-associated complications of cardiovascular and
      metabolic origin, which hamper both lifespan and quality of life, are positively
      influenced by the diet. Lastly, with regular monitoring jointly assumed by
      physicians and dietitians, nutritional status is well preserved as confirmed by a
      very low mortality rate and by the absence of detrimental effect on the long-term
      outcome of patients once renal replacement therapy is initiated. On account of
      its feasibility, efficacy and safety, sVLPD deserves a place in the management of
      selected patients to safely delay the time needed for dialysis.

PMID- 24016155
TI  - Foreground-background discrimination indicated by event-related brain potentials
      in a new auditory multistability paradigm.
AB  - For studying multistable auditory perception, we propose a paradigm that evokes
      integrated or segregated perception of a sound sequence, and permits
      decomposition of the segregated grouping into foreground and background sounds.
      The paradigm combines 3-tone pitch patterns with alternating timbres, resulting
      in a repeating 6-tone structure that can be perceived as rising based on temporal
      proximity, or as falling based on timbre similarity. Listeners continuously
      report their percept while EEG is recorded. Results show an ERP modulation
      starting at ~70 ms after sound onset that can be explained by whether a sound
      belongs to perceived foreground or background, with no additional effect of
      integrated versus segregated grouping. Auditory grouping as indexed by the
      mismatch negativity did not correspond with reported sound grouping. The paradigm
      offers a new possibility for investigating effects of conscious perceptual
      organization on sound processing. 

PMID- 24016156
TI  - Beliefs about the causes of success in sports and susceptibility for doping use
      in adolescent athletes.
AB  - The present study set out to assess the impact of attributional beliefs about
      success on the susceptibility for doping use in adolescent athletes. The sample
      consisted of 309 adolescent athletes participating in both team and individual
      sports. Participants completed a battery of questionnaires including Beliefs
      about the Causes of Success in Sport Questionnaire (BACSSQ), current and past
      doping use, and measures of attitudes, norms, situational temptation and social
      desirability. Variance reduction rate analysis revealed that social desirability
      did not act as a confounder in the relationship between doping susceptibility and
      its predictors. With regard to beliefs about the causes of success dimensions,
      only deception emerged as a significant predictor of doping use susceptibility
      over and above the effects of well-established social-cognitive predictors of
      doping intentions and use. These findings imply that beliefs about the causes of
      success in youth sports may comprise another dimension of risk factors for doping
      susceptibility and use.

PMID- 24016157
TI  - Drive for dough. PGA Tour Golfers' tee shot functional accuracy, distance and
      hole score.
AB  - A player's ability to score low is critical to the tournament outcome in golf.
      The relationships of round scores to fairways hit in regulation or striking
      distance on two holes per round have been investigated before with some
      disagreement. The purpose is therefore to examine the relationships of par-4 and
      par-5 hole scores to tee shot functional accuracy and distance, measured as lie
      of the ball and penalty, and striking distance or distance to the pin for the
      second shot. Such information is possible to collect without interviewing
      players. The best US Professional Golfers' Association Tour players' statistics
      during a season are used, provided by the Professional Golfers' Association Tour
      and ShotLink. Distance was measured with laser equipment. The results include
      significant (P < 0.05) correlations between score and striking distance or
      distance to pin, when hitting rough but not fairway on par-4s and when hitting
      fairway and rough on par-5s. It is therefore relevant, for performance, to
      consider the type of fairway miss as well as the striking distance in relation to
      the par and length of the hole. The findings can be considered when making gap
      and needs profiles, and when making tactical decisions for tee shots on different
      types of holes.

PMID- 24016159
TI  - Robustness of Salmonella loop-mediated isothermal amplification assays for food
      applications.
AB  - AIMS: Loop-mediated isothermal amplification (LAMP) assays have been developed
      recently for Salmonella detection. This study aimed at evaluating the robustness
      of two Salmonella LAMP assays in comparison with PCR and real-time quantitative
      PCR for food applications. METHODS AND RESULTS: Performance of the assays was
      examined under abusive preparation conditions, running temperatures and pH, and
      with the addition of various inhibitors and food rinses. LAMP achieved robust
      detection under abusive assay preparation conditions (holding at 22 and 37
      degrees C for up to 30 min) and running temperatures (57-68 degrees C). With a
      hot-start DNA polymerase, PCR obtained comparable results under these temperature
      ranges. However, PCR performed markedly poorer under abusive pH. LAMP also showed
      greater tolerance to potential inhibitors than PCR. When food rinses including
      meat juice, chicken rinse, egg homogenate and produce homogenate were added at
      20% of the reaction mix, PCR amplifications were completely inhibited, but LAMP
      reactions were not. CONCLUSIONS: Our results demonstrated that LAMP is a robust
      alternative to PCR in Salmonella detection for food applications. SIGNIFICANCE
      AND IMPACT OF THE STUDY: This study filled important knowledge gaps regarding the
      robustness of Salmonella LAMP assays. The findings will help bring Salmonella
      LAMP assays closer to wider applications in food testing.

PMID- 24016158
TI  - Electrophysiological correlates of episodic migraine chronification: evidence for
      thalamic involvement.
AB  - BACKGROUND: Episodic migraine is characterized by decreased high-frequency
      somatosensory oscillations (HFOs), reflecting thalamo-cortical activity, and
      deficient habituation of low-frequency (LF-) somatosensory evoked potentials
      (SSEPs) to repetitive sensory stimulation between attacks. Here, we study
      conventional LF-SSEPs and HFOs in episodic migraineurs who developed chronic
      migraine (CM). METHODS: Thirty-four episodic (15 interictally [MOii], 19 ictally
      [MOi]) and 19 CM patients underwent right median nerve SSEPs. The patient groups
      were compared to a group of 20 healthy volunteers (HV) of comparable age and
      gender distribution. We measured the N20-P25 LF-SSEP 1st amplitude block and
      habituation, and, after applying a band-pass filter (450-750 Hz), maximal peak-to
      peak latency and the amplitudes of the early and late HFOs. RESULTS: Reduced
      early HFOs, lower 1st block LF-SSEPs and deficient habituation characterize MOii.
      Initially higher SSEP amplitudes and late normal habituation characterize both CM
      and MOi patients. After the digital filtration, both patient groups showed
      shortened latency peaks and normalization of early HFO amplitudes with increased
      late HFOs. When data of MO and CM patients were combined, the monthly number of
      days with headache negatively correlated with the LF-SSEP slope (r = -0.385, p =
      0.006), which in turn negatively correlated with the 1st amplitude block (r =
      0.568, p < 0.001). CONCLUSIONS: Our results show abnormalities in chronic
      migraine that are also reported during attacks in episodic migraineurs, namely
      early response sensitization and late habituation. The HFO analysis suggests that
      this sensory sensitization may be explained by an increase in the strength of the
      connections between the thalamus and cortex compared to episodic migraine between
      attacks. Whether this electro-functional behaviour is primary or secondary to
      daily headache, thus reflecting an electrophysiological fingerprint of the
      somatosensory system central sensitization process, remains to be determined.

PMID- 24016160
TI  - Zinc(II) and cadmium(II) monohydroxide bridged, dinuclear metallacycles: a unique
      case of concerted double Berry pseudorotation.
AB  - The reactions of M(ClO4)2.6H2O [M = Zn(II), Cd(II)] and the ligands m-bis[bis(1
      pyrazolyl)methyl]benzene, L(m), or m-bis[bis(3,5-dimethyl-1
      pyrazolyl)methyl]benzene, L(m)*, in the presence of a base yield the hydroxide
      bridged dinuclear metallacycles [M2(MU-OH)(MU-L)2](ClO4)3, L = L(m), M = Zn(II)
      (1); L = L(m)*, M = Zn(II) (2), Cd(II) (3). In the solid state, the coordination
      environment of the metals is distorted trigonal bipyramidal with the bridging
      hydroxide in an equatorial position and M-O-M angles greater than 161 degrees .
      The observation of two equal intensity resonances for each type of pyrazolyl-ring
      hydrogen in the (1)H NMR for all three complexes coupled with the determination
      of the hydrodynamic radius based on the diffusion coefficient of 1 that matches
      that observed in the crystal structure, demonstrate this structure is retained in
      solution. Additional proof of the dinuclear structures in solution is given by
      the (113)Cd NMR spectrum of [Cd2(MU-OH)(MU-L(m)*)2](ClO4)3 showing (111/113)Cd
      satellites (J(111)(Cd-)(113)(Cd) = 173 Hz). Complex 1 is dynamic in solution,
      with the resonances for each type of pyrazolyl-ring hydrogen broadening and
      averaging at higher temperatures. Detailed variable temperature studies show that
      DeltaG(pz)(?) = 15.2(+/-0.2) kcal/mol, DeltaH(pz)(?) = 6.6(+/-0.1) kcal/mol, and
      DeltaS(pz)(?) = -28.8(+/-0.4) cal/mol.K at 25  degrees C for this process. The
      same DeltaG(?) value for the dynamic process was also determined by saturation
      transfer experiments. The most plausible mechanism for this dynamic process,
      which exchanges the axial and equatorial positions of the pyrazolyl rings in the
      trigonal bipyramidal arrangement, involves Berry pseudorotation at both metal
      sites using the bridging oxygen atom as the pivot ligand, coupled with the ring
      flip of the ligand's phenylene spacer by 180 degrees , a rearrangement process we
      termed the "Columbia Twist and Flip". This process was shown to be influenced by
      trace amounts of water in the solvent, with a linear relationship between the
      water concentration and DeltaG(pz)(?); increasing the water concentration lowers
      DeltaG(pz)(?). Spin saturation transfer experiments demonstrated the exchange of
      the hydrogens between the water in the solvent and the bridging hydroxide group,
      with DeltaG(OH)(?) = 16.8(+/-0.2) kcal/mol at 25  degrees C, a value larger than
      the barrier of DeltaG(pz)(?) = 15.2(+/-0.2) kcal/mol for the "Columbia Twist and
      Flip". Compounds 2 and 3 do not show dynamic behavior involving the pyrazolyl
      rings in solution because of steric crowding caused by the methyl group
      substitution, but do show the exchange between the water in the solvent and the
      bridging hydroxide group.

PMID- 24016162
TI  - Assessing the assessment of interventions: we're not there yet.

PMID- 24016163
TI  - Why the conception of the doctor as applied scientist is inadequate.

PMID- 24016164
TI  - What is the evidence for clinical placements in underserved areas?

PMID- 24016165
TI  - When I say ... test-enhanced learning.

PMID- 24016166
TI  - Cost analyses approaches in medical education: there are no simple solutions.
AB  - CONTEXT: Medical education is expensive. Although we have made progress in
      working out 'what works' in medical education, there are few data on whether
      medical education offers value relative to cost. Research into cost and value in
      medical education is beset by problems. One of the major problems is the lack of
      clear definitions for many of the terms commonly used. Phrases such as cost
      effectiveness analysis, cost-benefit analysis, cost-utility analysis and cost
      feasibility analysis are used without authors explaining to readers what they
      mean (and sometimes without authors themselves understanding what they mean).
      Sometimes such terms are used interchangeably and sometimes they are used as
      rhetorical devices without any real evidence that backs up such rhetoric as to
      the cost-effectiveness or otherwise of educational interventions. The frequent
      misuse of these terms is surprising considering the importance of the topics
      under consideration and the need for precision in many aspects of medical
      education. METHODS: Here we define commonly used terms in cost analyses and give
      examples of their usage in the context of medical education. CONCLUSIONS: Cost
      effectiveness analysis refers to the evaluation of two or more alternative
      educational approaches or interventions according to their costs and their
      effects in producing a certain outcome. Cost-benefit analysis refers to 'the
      evaluation of alternatives according to their costs and benefits when each is
      measured in monetary terms'. Cost-utility analysis is the examination of two or
      more alternatives according to their cost and their utility. In this context,
      utility means the satisfaction among individuals as a result of one or more
      outcome or the perceived value of the expected outcomes to a particular
      constituency. Cost-feasibility analysis involves simply measuring the cost of a
      proposed intervention in order to decide whether it is feasible.

PMID- 24016167
TI  - A systematic literature review of undergraduate clinical placements in
      underserved areas.
AB  - CONTEXT: The delivery of undergraduate clinical education in underserved areas is
      increasing in various contexts across the world in response to local workforce
      needs. A collective understanding of the impact of these placements is lacking.
      Previous reviews have often taken a positivist approach by only looking at
      outcome measures. This review addresses the question: What are the strengths and
      weaknesses for medical students and supervisors of community placements in
      underserved areas? METHODS: A systematic literature review was carried out by
      database searching, citation searching, pearl growing, reference list checking
      and use of own literature. The databases included MEDLINE, EMBASE, PsycINFO, Web
      of Science and ERIC. The search terms used were combinations and variations of
      four key concepts exploring general practitioner (GP) primary care, medical
      students, placements and location characteristics. The papers were analysed using
      a textual narrative synthesis. FINDINGS: The initial search identified 4923
      results. After the removal of duplicates and the screening of titles and
      abstracts, 185 met the inclusion criteria. These full articles were obtained and
      assessed for their relevance to the research question; 54 were then included in
      the final review. Four main categories were identified: student performance,
      student perceptions, career pathways and supervisor experiences. CONCLUSIONS:
      This review reflects the emergent qualitative data as well as the quantitative
      data used to assess initiatives. Underserved area placements have produced many
      beneficial implications for students, supervisors and the community. There is a
      growing amount of evidence regarding rural, underserved areas, but little in
      relation to inner city, deprived areas, and none in the UK.

PMID- 24016168
TI  - The roles of deliberate practice and innate ability in developing expertise:
      evidence and implications.
AB  - CONTEXT: Medical education research focuses extensively on experience and
      deliberate practice (DP) as key factors in the development of expert performance.
      The research on DP minimises the role of individual ability in expert
      performance. This claim ignores a large body of research supporting the
      importance of innate individual cognitive differences. We review the relationship
      between DP and an innate individual ability, working memory (WM) capacity, to
      illustrate how both DP and individual ability predict expert performance.
      METHODS: This narrative review examines the relationship between DP and WM in
      accounting for expert performance. Studies examining DP, WM and individual
      differences were identified through a targeted search. RESULTS: Although all
      studies support extensive DP as a factor in explaining expertise, much research
      suggests individual cognitive differences, such as WM capacity, predict expert
      performance after controlling for DP. The extent to which this occurs may be
      influenced by the nature of the task under study and the cognitive processes used
      by experts. The importance of WM capacity is greater for tasks that are non
      routine or functionally complex. Clinical reasoning displays evidence of this
      task-dependent importance of individual ability. CONCLUSIONS: No single factor is
      both necessary and sufficient in explaining expertise, and individual abilities
      such as WM can be important. These individual abilities are likely to contribute
      to expert performance in clinical settings. Medical education research and
      practice should identify the individual differences in novices and experts that
      are important to clinical performance.

PMID- 24016169
TI  - More than communication skills: experiences of communication conflict in nursing
      home nurses.
AB  - CONTEXT: Communication conflicts are inevitable in nursing homes. Understanding
      communication conflicts experienced by practising nurses could provide insights
      to guide the development of sound communication education programmes. OBJECTIVES:
      The purpose of this study was to explore the experiences of nurses in nursing
      homes of communication conflict in encounters with nursing home residents and
      their families in Taiwan. METHODS: Data were collected from April 2010 to
      December 2011 through audiotaped, individual, in-depth interviews with 26 nurses
      at five nursing homes in Taiwan. Data were analysed according to van Manen's
      interpretive phenomenological method. RESULTS: Data analysis revealed that
      nurses' experiences of communication conflicts during encounters with nursing
      home residents and their families could be categorised under three themes:
      differences in perspectives of nursing home services; differences in views of
      nurturing health, and mediation between family members and others. CONCLUSIONS:
      The findings of this study can be considered by clinical educators and
      policymakers when designing communication education programmes for nurses and
      other clinicians. These programmes should include ways to increase nurses'
      independent thinking in settings in which power differences exist, as well as
      their cultural sensitivity as embodied in Leininger's culture care theory. These
      programmes should also include education in telephone communication and
      alternative methods of communication (e.g. videoconferencing).

PMID- 24016170
TI  - Medical students' health-related quality of life: roles of social and behavioural
      factors.
AB  - OBJECTIVES: The long and demanding course of medical education may be accompanied
      by distress with serious consequences. This study was conducted to assess the
      multidimensional health-related quality of life (HR-QoL) in medical students in
      different stages of medical education and its associations with behavioural and
      social factors. METHODS: A cross-sectional study was conducted in medical
      students at three medical schools at, respectively, Tehran University of Medical
      Sciences, Aja University of Medical Sciences and Baghiyatalah Medical School, in
      November and December 2011 using stratified sampling. Data were obtained on
      participants' characteristics, including gender, current education stage, living
      situation, smoking status, physical activity, and membership of associations or
      teams. Health-related QoL was measured using the Persian version of the 36-item
      Short Form Health Survey (SF-36), which generates a physical component score
      (PCS) and a mental component score (MCS). Logistic regression was applied to
      measure the adjusted associations between variables. RESULTS: Of the 1350
      students invited, 1086 individuals completed the survey to give a response rate
      of 80.4%. Logistic regression showed male gender (odds ratio [OR] = 2.88, p <
      0.001), living with family versus in a dormitory (OR = 2.72, p < 0.001) and
      participation in daily physical activity (OR = 16.96, p < 0.001) to be
      significantly associated with a higher PCS. Being in an internship versus in the
      basic sciences stage of medical education showed a significant association with a
      lower PCS (OR = 0.12, p < 0.001). Similarly, male gender (OR = 1.67, p < 0.05),
      living with family rather than in a dormitory (OR = 16.91, p < 0.001), daily
      physical activity (OR = 25.36, p < 0.001), and membership of associations or
      teams (OR = 3.67, p < 0.001) were associated with a higher MCS. Likewise,
      studying in internship rather than in the basic sciences stage was accompanied by
      a lower MCS (OR = 0.12, p < 0.001). CONCLUSIONS: This large, multi-institution
      study, despite its limitations, indicates that medical students in internships
      show lower scores in all domains of QoL. Social engagement is an important
      associate of higher HR-QoL. Further studies should address the efficacy of
      interventions, such as self-awareness programmes and initiatives to encourage
      students to be more physically and socially active, in improving students'
      health.

PMID- 24016171
TI  - Can taking a nap during a night shift counteract the impairment of executive
      skills in residents?
AB  - OBJECTIVES: Long and repeated periods of sustained wakefulness constitute a
      serious problem for shift workers in general and for medical interns in
      particular. In a real clinical setting, we investigated whether taking a long nap
      can counteract the negative consequences of acute sleep deprivation on executive
      skills in residents. METHODS: Fifty-four interns at the Faculty of Medicine of
      the University of L'Aquila (Italy) participated in the study. Thirty-two
      participants who worked the night shift were assigned to a wake or nap group (WG,
      NG). The remaining 22 participants, who maintained regular diurnal working hours,
      were assigned to a control sleep group (SG). Each participant performed task
      switching and go/no-go tasks in three sessions, carried out on 3 consecutive
      days, to provide baseline and experimental (after the night shift [WG and NG])
      data and data subsequent to having a normal night's sleep at home (SG) and
      subsequent to recovery (after a night's sleep at home). The dependent variables
      were submitted to a mixed-model analysis of variance (anova). RESULTS: After the
      night shift, SG and NG participants demonstrated better performance speed at task
      switching than WG participants. Moreover, WG participants showed lower accuracy
      throughout the study protocol compared with SG and NG participants. CONCLUSIONS:
      Taking a long nap proved to be effective in ameliorating the deterioration in
      executive skills that accompanies night shift-working in interns. This finding
      raises the two entwined issues of how long a nocturnal nap should be and when it
      should best occur in order to support the maintenance of an effective process of
      consolidation of new executive skills.

PMID- 24016172
TI  - Medical education and moral segmentation in medical students.
AB  - CONTEXT: Many studies indicate that increases in cognitive ability, maturity and
      educational experience lead to a general increase in moral reasoning skills.
      However, research has shown that moral development does not occur during medical
      school and that it may, in fact, plateau or even regress. There is no empirical
      evidence as to what might be the cause of such a result. OBJECTIVES: The present
      study aimed to assess moral judgement competence in medical students and to
      investigate trends in moral judgement competence in relation to age, gender,
      culture, religion, year of medical course and different programmes within the
      medical curriculum. METHODS: We employed a cross-sectional and descriptive design
      over two consecutive years (2011 and 2012). Students completed Lind's Moral
      Judgement Test (MJT), which is based on Kohlberg's stages of moral development
      and is used to measure moral judgement competence (C-INDEX). C-INDEX results were
      analysed in relation to age, gender, cultural background, religion, cohort and
      specific programmes within the medical curriculum. RESULTS: The numbers of
      students who completed the MJT in 2011 and 2012 were 394 and 486, respectively.
      The two studies showed a significant difference and negative correlations between
      the moral judgement competence of medical students and both age and year of
      medical course (p < 0.001). The findings suggested the existence of a phenomenon
      known as 'moral segmentation', which increased significantly as students
      progressed through medical education, and were significantly linear between
      cohorts. CONCLUSIONS: Students show a decline in moral judgement competence
      during medical education. This probably reflects an increase in moral
      segmentation rather than an inhibition in moral development. The challenge is to
      develop a curriculum that will enable medical students to maintain, or better,
      increase their moral judgement competence.

PMID- 24016173
TI  - Analysis of field reports from anaesthesia volunteers in low- to middle-income
      countries.
AB  - OBJECTIVES: The objective of this study was to identify key experiences and
      common motifs of volunteer doctors who have participated in anaesthesia-related
      volunteer experiences abroad through the Health Volunteers Overseas (HVO)
      programme. An additional goal was to understand the effects of medical
      volunteerism in developing countries on the volunteers themselves. METHODS: After
      a medical mission with HVO, anaesthesia volunteers submit a post-experience
      report. Twenty-five reports were randomly selected from the 58 available trip
      reports, including five from each of the five countries collaborating with HVO.
      Data in the reports were analysed using a modified grounded theory and constant
      comparative technique until thematic saturation was achieved. RESULTS: Three
      major discoveries emerged from the analysis of post-experience reports: (i)
      anaesthesia residents and attending physicians find their volunteer experiences
      in the developing world to be personally rewarding and positive; (ii) most
      participants feel their educational interventions have a positive impact on local
      students and anaesthesia providers, and (iii) global volunteerism poses
      challenges, primarily caused by lack of resource availability and communication
      issues. CONCLUSIONS: Our results give new insight into the experiences of and
      challenges faced by a cohort of HVO-sponsored anaesthesia volunteers while abroad
      and validates the positive effects these global health experiences have on the
      volunteers themselves. This group of anaesthesia volunteers was able to further
      their personal and professional growth, sharpen their physical diagnosis and
      clinical reasoning skills in resource-poor environments and, most importantly,
      provide education and promote an exchange of ideas and information.

PMID- 24016174
TI  - Confronting the caring crisis in clinical practice.
AB  - CONTEXT: In light of the call for humanistic caring in the contemporary health
      care system globally and in China, the issue of improving the caring skills that
      are essential to student success, high-quality nursing practice and positive
      patient outcomes is at the forefront of nursing education. OBJECTIVES: The aim of
      this mixed-methods quantitative and qualitative study was to investigate
      baccalaureate nursing students' caring ability in the context of China and to
      explore the role of clinical practice learning in the development of students'
      caring skills. METHODS: A two-phase, descriptive study utilising a mixed
      methodology consisting of a caring ability survey and focus group interviews was
      conducted. In the quantitative phase, 598 baccalaureate nursing students at two
      colleges in Yunnan Province in southwest China were surveyed using the Caring
      Ability Inventory (CAI). In the qualitative phase, 16 of the students who had
      participated in the quantitative phase were interviewed. RESULTS: Students
      obtained lower scores on the CAI than have been reported elsewhere by other
      researchers. In addition, students in the clinical stage of training scored lower
      than students in the pre-clinical stage. Three themes concerning facilitation by
      and three themes concerning the obstructive effects of clinical practice learning
      in the development of caring ability were identified. Themes pertaining to
      facilitation were: (i) promoting a sense of professional responsibility and
      ethics; (ii) providing an arena in which to practise caring, and (iii) learning
      from positive role models. Themes pertaining to obstruction were: (i) a critical
      practice learning environment; (ii) encountering inappropriate clinical teachers,
      and (iii) experiencing shock at the contrast between an idealised and the real
      environment. CONCLUSIONS: The key to developing students' ability to care lies in
      highlighting caring across the entire health care system. By diminishing exposure
      to negative role models, and adopting appropriate pedagogical ideas about
      education in caring, such as truth telling and helping students to think in a
      critical manner, educators can help students to improve their caring ability.

PMID- 24016175
TI  - MB/PhD training in the UK: towards embracement.

PMID- 24016176
TI  - The cultural flavours of problem-based learning.

PMID- 24016177
TI  - Combining fossil and molecular data to date the diversification of New World
      Primates.
AB  - Recent methodological advances in molecular dating associated with the growing
      availability of sequence data have prompted the study of the evolution of New
      World Anthropoidea in recent years. Motivated by questions regarding historical
      biogeography or the mode of evolution, these works aimed to obtain a clearer
      scenario of Platyrrhini origins and diversification. Although some consensus was
      found, disputed issues, especially those relating to the evolutionary affinities
      of fossil taxa, remain. The use of fossil taxa for divergence time analysis is
      traditionally restricted to the provision of calibration priors. However, new
      analytical approaches have been developed that incorporate fossils as terminals
      and, thus, directly assign ages to the fossil tips. In this study, we conducted a
      combined analysis of molecular and morphological data, including fossils, to
      derive the timescale of New World anthropoids. Differently from previous studies
      that conducted total-evidence analysis of molecules and morphology, our approach
      investigated the morphological clock alone. Our results corroborate the
      hypothesis that living platyrrhines diversified in the last 20 Ma and that
      Miocene Patagonian fossils compose an independent evolutionary radiation that
      diversified in the late Oligocene. When compared to the node ages inferred from
      the molecular timescale, the inclusion of fossils augmented the precision of the
      estimates for nodes constrained by the fossil tips. We show that morphological
      data can be analysed using the same methodological framework applied in relaxed
      molecular clock studies. 

PMID- 24016178
TI  - Functional genetic polymorphisms in CYP2C19 gene in relation to cardiac side
      effects and treatment dose in a methadone maintenance cohort.
AB  - Abstract Methadone maintenance therapy is an established treatment for heroin
      dependence. This study tested the influence of functional genetic polymorphisms
      in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism
      on treatment dose, plasma concentration, and side effects of methadone. Two
      single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon
      5), were selected and genotyped in 366 patients receiving methadone maintenance
      therapy in Taiwan. The steady-state plasma concentrations of both methadone and
      its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was
      significantly associated with the corrected QT interval (QTc) change in the
      electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS)
      total score (p=0.021) in patients who continued using heroin, as demonstrated
      with a positive urine opiate test. Using the gene dose (GD) models where the
      CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and
      extensive (2 GD) metabolizers, we found that the extensive metabolizers required
      a higher dose of methadone (p=0.035), and showed a lower plasma R
      methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients,
      as well as a greater QTc change (p=0.008) and higher total scores of TESS
      (p=0.018) in urine opiate test positive patients, than poor metabolizers. These
      results in a large study sample from Taiwan suggest that the gene dose of CYP2C19
      may potentially serve as an indicator for the plasma R-methadone/methadone dose
      ratio and cardiac side effect in patients receiving methadone maintenance
      therapy. Further studies of pharmacogenetic variation in methadone
      pharmacokinetics and pharmacodynamics are warranted in different world
      populations. 

PMID- 24016180
TI  - 14-3-3 Protein in CSF reflects SIV-mediated pre-synaptic damage.
AB  - HIV-associated neurocognitive disorders (HAND) remain prevalent despite effective
      combined anti-retroviral therapy (cART). Cognitive function has been shown to
      inversely correlate with decreased synaptic and dendritic density. In this study,
      macaques inoculated with SIV were examined over a 3-month course of infection to
      characterize the appearance of the neuronal damage marker 14-3-3 protein in CSF
      and to determine whether CSF 14-3-3 levels directly reflected synaptic
      alterations. SIV-infected macaques with 14-3-3 in CSF had significantly lower
      levels of the presynaptic protein synaptophysin in cortical grey matter.
      Synaptophysin levels were inversely correlated with amount of SIV RNA in the CNS.
      In contrast, levels of 14-3-3 in CSF did not correspond with either alterations
      in levels of the postsynaptic protein PSD-95 or viral replication in the brain.
      These findings suggest that the appearance of 14-3-3 in CSF during asymptomatic
      infection reflects pre-synaptic damage in SIV-infected macaques and thus may
      serve as a marker of the early synaptic alterations that underlie HIV-induced
      neurocognitive impairment. 

PMID- 24016179
TI  - Selective nucleic acid removal via exclusion (SNARE): capturing mRNA and DNA from
      a single sample.
AB  - The path from gene (DNA) to gene product (RNA or protein) is the foundation of
      genotype giving rise to phenotype. Comparison of genomic analyses (DNA) with
      paired transcriptomic studies (mRNA) is critical to evaluating the pathogenic
      processes that give rise to human disease. The ability to analyze both DNA and
      mRNA from the same sample is not only important for biologic interrogation but
      also to minimize variance (e.g., sample loss) unrelated to the biology. Existing
      methods for RNA and DNA purification from a single sample are typically time
      consuming and labor intensive or require large sample sizes to split for separate
      RNA and DNA extraction procedures. Thus, there is a need for more efficient and
      cost-effective methods to purify both RNA and DNA from a single sample. To
      address this need, we have developed a technique, termed SNARE (Selective Nucleic
      Acid Removal via Exclusion), that uses pinned oil interfaces to simultaneous
      purify mRNA and DNA from a single sample. A unique advantage of SNARE is the
      elimination of dilutive wash and centrifugation processes that are fundamental to
      conventional methods where sample is typically discarded. This minimizes loss and
      maximizes recovery by allowing nondilutive reinterrogation of the sample. We
      demonstrate that SNARE is more sensitive than commercially available kits,
      robustly and repeatably achieving mRNA and DNA purification from extremely low
      numbers of cells for downstream analyses. In addition to sensitivity, SNARE is
      fast, easy to use, and cost-effective and requires no laboratory infrastructure
      or hazardous chemicals. We demonstrate the clinical utility of the SNARE with
      prostate cancer circulating tumor cells to demonstrate its ability to perform
      both genomic and transcriptomic interrogation on rare cell populations that would
      be difficult to achieve with any current method. 

PMID- 24016181
TI  - On the asymptotic standard error of a class of robust estimators of ability in
      dichotomous item response models.
AB  - In item response theory, the classical estimators of ability are highly sensitive
      to response disturbances and can return strongly biased estimates of the true
      underlying ability level. Robust methods were introduced to lessen the impact of
      such aberrant responses on the estimation process. The computation of asymptotic
      (i.e., large-sample) standard errors (ASE) for these robust estimators, however,
      has not yet been fully considered. This paper focuses on a broad class of robust
      ability estimators, defined by an appropriate selection of the weight function
      and the residual measure, for which the ASE is derived from the theory of
      estimating equations. The maximum likelihood (ML) and the robust estimators,
      together with their estimated ASEs, are then compared in a simulation study by
      generating random guessing disturbances. It is concluded that both the estimators
      and their ASE perform similarly in the absence of random guessing, while the
      robust estimator and its estimated ASE are less biased and outperform their ML
      counterparts in the presence of random guessing with large impact on the item
      response process. 

PMID- 24016182
TI  - Glyco-analytical multispecific proteolysis (Glyco-AMP): a simple method for
      detailed and quantitative Glycoproteomic characterization.
AB  - Despite recent advances, site-specific profiling of protein glycosylation remains
      a significant analytical challenge for conventional proteomic methodology. To
      alleviate the issue, we propose glyco-analytical multispecific proteolysis (Glyco
      AMP) as a strategy for glycoproteomic characterization. Glyco-AMP consists of
      rapid, in-solution digestion of an analyte glycoprotein (or glycoprotein mixture)
      by a multispecific protease (or protease cocktail). Resulting glycopeptides are
      chromatographically separated by isomer-specific porous graphitized carbon nano
      LC, quantified by high-resolution MS, and structurally elucidated by MS/MS. To
      demonstrate the consistency and customizability of Glyco-AMP methodology, the
      glyco-analytical performances of multispecific proteases subtilisin, pronase, and
      proteinase K were characterized in terms of quantitative accuracy, sensitivity,
      and digestion kinetics. Glyco-AMP was shown be effective on glycoprotein mixtures
      as well as glycoproteins with multiple glycosylation sites, providing detailed,
      quantitative, site- and structure-specific information about protein
      glycosylation. 

PMID- 24016183
TI  - Assessing the Safety Attitudes Questionnaire (SAQ), German language version in
      Swiss university hospitals--a validation study.
AB  - BACKGROUND: Improving patient safety has become a major focus of clinical care
      and research over the past two decades. An institution's patient safety climate
      represents an essential component of ensuring a safe environment and thereby can
      be vital to the prevention of adverse events. Covering six patient safety related
      factors, the Safety Attitudes Questionnaire (SAQ) is a validated and widely used
      instrument to measure the patient safety climate in clinical areas. The objective
      of this study was to assess the psychometric properties of the German language
      version of the SAQ. METHODS: A survey was carried out in two University Hospitals
      in Switzerland in autumn 2009 where the SAQ was distributed to a sample of 406
      nurses and physicians in medical and surgical wards. Following the American
      Educational Research Association guidelines, we tested the questionnaire validity
      by levels of evidence: content validity, internal structure and relations to
      other variables. Confirmatory factor analysis was used to examine factor
      structure. Cronbach's alphas and inter-item correlations were calculated to
      examine internal consistency reliability. RESULTS: A total of 319 questionnaires
      were completed representing an overall response rate of 78.6%. For three items,
      the item content validity index was <0.75. Confirmatory factor analysis showed
      acceptable model fit (RMSEA = 0.045; CFI = 0.944) for the six-factor model.
      Additional exploratory factor analysis could not identify a better factor model.
      SAQ factor scores showed positive correlations with the Safety Organizing Scale
      (r = .56-.72). The SAQ German version showed moderate to strong internal
      consistency reliability indices (Cronbach alpha = .65-.83). CONCLUSIONS: The
      German language version of the SAQ demonstrated acceptable to good psychometric
      properties and therefore shows promise to be a sound instrument to measure
      patient safety climate in Swiss hospital wards. However, the low item content
      validity and large number of missing responses for several items suggest that
      improvements and adaptations in translation are required for select items,
      especially within the perception of management scale. Following these revisions,
      psychometric properties should reassessed in a randomly selected sample and
      hospitals and departments prior to use in Swiss hospital settings.

PMID- 24016184
TI  - Gate-controlled spin-orbit interaction in inas high-electron mobility transistor
      layers epitaxially transferred onto Si substrates.
AB  - We demonstrate gate-controlled spin-orbit interaction (SOI) in InAs high-electron
      mobility transistor (HEMT) structures transferred epitaxially onto Si substrates.
      Successful epitaxial transfer of the multilayered structure after separation from
      an original substrate ensures that the InAs HEMT maintains a robust bonding
      interface and crystalline quality with a high electron mobility of 46200 cm(2)/(V
      s) at 77 K. Furthermore, Shubnikov-de Haas (SdH) oscillation analysis reveals
      that a Rashba SOI parameter (alpha) can be manipulated using a gate electric
      field for the purpose of spin field-effect transistor operation. An important
      finding is that the alpha value increases by about 30% in the InAs HEMT structure
      that has been transferred when compared to the as-grown structure. First
      principles calculations indicate that the main causes of the large improvement in
      alpha are the bonding of the InAs HEMT active layers to a SiO2 insulating layer
      with a large band gap and the strain relaxation of the InAs channel layer during
      epitaxial transfer. The experimental results presented in this study offer a
      technological platform for the integration of III-V heterostructures onto Si
      substrates, permitting the spintronic devices to merge with standard Si circuitry
      and technology. 

PMID- 24016186
TI  - Practical ring-opening strategy for the sequence determination of cyclic peptides
      from one-bead-one-compound libraries.
AB  - The use of cyclic peptides in one-bead-one-compound libraries is limited by
      difficulties in sequencing hit compounds. Lacking a free N-terminal amine, such
      peptides cannot be sequenced by the Edman degradation approach, and complex
      fragmentation patterns are obtained by tandem mass spectrometry. To overcome this
      problem, we designed an alternative approach introducing a methionine residue
      within the macrocycle and as a linker to allow simultaneous ring-opening and
      release from the resin upon treatment with cyanogen bromide. The methionine
      linker was inverted relative to the peptide chain to allow the synthesis of
      cyclic peptides anchored by a lysine side chain and to avoid the presence of two
      C-terminal homoserine lactones on the released linear peptides. After MALDI-TOF
      MS/MS analysis, the peptides released from a single bead were sequenced manually
      and with a de novo sequencing software. The strategy described herein is
      compatible with commonly used amino acids and allows sequencing of cyclic
      peptides in one-bead-one-compound libraries, thus reducing the need for encoding.

PMID- 24016185
TI  - Characterizing the syphilis epidemic among men who have sex with men in Lima,
      Peru to identify new treatment and control strategies.
AB  - BACKGROUND: Syphilis is an important sexually transmitted infection (STI) with
      serious public health consequences. Among men who have sex with men (MSM) in
      Lima, the prevalence and incidence are extraordinarily high. Current syndromic
      approaches, however, fail to identify asymptomatic cases, and in settings where
      large proportions of individuals test positive again after treatment, it is
      frequently difficult to distinguish treatment failure from re-infection. Thus,
      new approaches are needed to improve treatment strategies and public health
      control efforts. METHODS/DESIGN: Study participants will undergo baseline testing
      for syphilis infection along with a behavioral survey covering demographics,
      sexual behavior, drug and alcohol abuse and health-care seeking behavior. The
      cohort will be followed for 18 months at three-month intervals. Blood and earlobe
      scrapings will also be collected for T. pallidum DNA testing, to create molecular
      markers for subtyping. We will also perform cytokine testing on collected samples
      in order to create host immunologic profiles associated with recurrence, re
      infection, treatment failure and success. DISCUSSION: Advances in social
      epidemiology, molecular typing and characterization of host immune responses will
      offer promise in developing new understandings of syphilis management. We will
      share our findings with the Peruvian Ministry of Health and other public health
      organizations, to identify new approaches of case detection and successful
      treatment.

PMID- 24016187
TI  - The digestive tract of Drosophila melanogaster.
AB  - The digestive tract plays a central role in the digestion and absorption of
      nutrients. Far from being a passive tube, it provides the first line of defense
      against pathogens and maintains energy homeostasis by exchanging neuronal and
      endocrine signals with other organs. Historically neglected, the gut of the fruit
      fly Drosophila melanogaster has recently come to the forefront of Drosophila
      research. Areas as diverse as stem cell biology, neurobiology, metabolism, and
      immunity are benefitting from the ability to study the genetics of development,
      growth regulation, and physiology in the same organ. In this review, we summarize
      our knowledge of the Drosophila digestive tract, with an emphasis on the adult
      midgut and its functional underpinnings. 

PMID- 24016189
TI  - SIR proteins and the assembly of silent chromatin in budding yeast.
AB  - Saccharomyces cerevisiae provides a well-studied model system for heritable
      silent chromatin in which a histone-binding protein complex [the SIR (silent
      information regulator) complex] represses gene transcription in a sequence
      independent manner by spreading along nucleosomes, much like heterochromatin in
      higher eukaryotes. Recent advances in the biochemistry and structural biology of
      the SIR-chromatin system bring us much closer to a molecular understanding of
      yeast silent chromatin. Simultaneously, genome-wide approaches have shed light on
      the biological importance of this form of epigenetic repression. Here, we
      integrate genetic, structural, and cell biological data into an updated overview
      of yeast silent chromatin assembly. 

PMID- 24016190
TI  - Genomic imprinting: insights from plants.
AB  - Imprinted gene expression--the biased expression of alleles dependent on their
      parent of origin--is an important type of epigenetic gene regulation in flowering
      plants and mammals. In plants, genes are imprinted primarily in the endosperm,
      the triploid placenta-like tissue that surrounds and nourishes the embryo during
      its development. Differential allelic expression is correlated with active DNA
      demethylation by DNA glycosylases and repressive targeting by the Polycomb group
      proteins. Imprinted gene expression is one consequence of a large-scale
      remodeling to the epigenome, primarily directed at transposable elements, that
      occurs in gametes and seeds. This remodeling could be important for maintaining
      the epigenome in the embryo as well as for establishing gene imprinting.

PMID- 24016188
TI  - Expanding horizons: ciliary proteins reach beyond cilia.
AB  - Once obscure, the cilium has come into the spotlight during the past decade. It
      is now clear that aside from generating locomotion by motile cilia, both motile
      and immotile cilia serve as signaling platforms for the cell. Through both
      motility and sensory functions, cilia play critical roles in development,
      homeostasis, and disease. To date, the cilium proteome contains more than 1,000
      different proteins, and human genetics is identifying new ciliopathy genes at an
      increasing pace. Although assigning a function to immotile cilia was a challenge
      not so long ago, the myriad of signaling pathways, proteins, and biological
      processes associated with the cilium have now created a new obstacle: how to
      distill all these interactions into specific themes and mechanisms that may
      explain how the organelle serves to maintain organism homeostasis. Here, we
      review the basics of cilia biology, novel functions associated with cilia, and
      recent advances in cilia genetics, and on the basis of this framework, we further
      discuss the meaning and significance of ciliary connections. 

PMID- 24016191
TI  - Regulation of bacterial metabolism by small RNAs using diverse mechanisms.
AB  - Bacteria live in many dynamic environments with alternating cycles of feast or
      famine that have resulted in the evolution of mechanisms to quickly alter their
      metabolic capabilities. Such alterations often involve complex regulatory
      networks that modulate expression of genes involved in nutrient uptake and
      metabolism. A great number of protein regulators of metabolism have been
      characterized in depth. However, our ever-increasing understanding of the roles
      played by RNA regulators has revealed far greater complexity to regulation of
      metabolism in bacteria. Here, we review the mechanisms and functions of selected
      bacterial RNA regulators and discuss their importance in modulating nutrient
      uptake as well as primary and secondary metabolic pathways. 

PMID- 24016192
TI  - The genotypic view of social interactions in microbial communities.
AB  - Dense and diverse microbial communities are found in many environments.
      Disentangling the social interactions between strains and species is central to
      understanding microbes and how they respond to perturbations. However, the study
      of social evolution in microbes tends to focus on single species. Here, we
      broaden this perspective and review evolutionary and ecological theory relevant
      to microbial interactions across all phylogenetic scales. Despite increased
      complexity, we reduce the theory to a simple null model that we call the
      genotypic view. This states that cooperation will occur when cells are surrounded
      by identical genotypes at the loci that drive interactions, with genetic identity
      coming from recent clonal growth or horizontal gene transfer (HGT). In contrast,
      because cooperation is only expected to evolve between different genotypes under
      restrictive ecological conditions, different genotypes will typically compete.
      Competition between two genotypes includes mutual harm but, importantly, also
      many interactions that are beneficial to one of the two genotypes, such as
      predation. The literature offers support for the genotypic view with relatively
      few examples of cooperation between genotypes. However, the study of microbial
      interactions is still at an early stage. We outline the logic and methods that
      help to better evaluate our perspective and move us toward rationally engineering
      microbial communities to our own advantage. 

PMID- 24016193
TI  - Control of nuclear activities by substrate-selective and protein-group
      SUMOylation.
AB  - Reversible modification of proteins by SUMO (small ubiquitin-like modifier)
      affects a large number of cellular processes. In striking contrast to the related
      ubiquitin pathway, only a few enzymes participate in the SUMO system, although
      this pathway has numerous substrates as well. Emerging evidence suggests that
      SUMOylation frequently targets entire groups of physically interacting proteins
      rather than individual proteins. Protein-group SUMOylation appears to be
      triggered by recruitment of SUMO ligases to preassembled protein complexes.
      Because SUMOylation typically affects groups of proteins that bear SUMO
      interaction motifs (SIMs), protein-group SUMOylation may foster physical
      interactions between proteins through multiple SUMO-SIM interactions. Individual
      SUMO modifications may act redundantly or additively, yet they may mediate
      dedicated functions as well. In this review, we focus on the unorthodox
      principles of this pathway and give examples for SUMO-controlled nuclear
      activities. We propose that collective SUMOylation is typical for nuclear
      assemblies and argue that SUMO serves as a distinguishing mark for functionally
      engaged protein fractions. 

PMID- 24016194
TI  - Electrocardiographic predictors of electroanatomic scar size in arrhythmogenic
      right ventricular cardiomyopathy: implications for arrhythmic risk
      stratification.
AB  - INTRODUCTION: The extent of right ventricular (RV) electroanatomic scar (EAS)
      detected by endocardial voltage mapping (EVM) is a powerful invasive predictor of
      arrhythmic outcome in patients with arrhythmogenic right ventricular
      cardiomyopathy (ARVC). Electrocardiogram (ECG) and signal-averaged ECG are
      noninvasive tools of established clinical value for the diagnosis of electrical
      abnormalities in ARVC. This study was designed to assess the role of ECG and
      SAECG abnormalities for noninvasive estimation of the extent and regional
      distribution of RV-EAS and prediction of scar-related arrhythmic risk. METHODS
      AND RESULTS: The study population included 49 consecutive patients (38 males,
      median age 35 years) with a definite diagnosis of ARVC and an abnormal EVM by
      CARTO system. At univariate analysis, the presence of epsilon waves, the degree
      of RV dilation, the severity of RV dysfunction, and the extent of negative T
      waves correlated with RV-EAS% area. Normal T-waves were associated with a median
      RV-EAS% area of 4.9% (4.5-6.4), negative T waves in V1-V3 of 22.0% (8.5-30.6),
      negative T waves in V1-V3 extending to lateral precordial leads (V4-V6) of 26.8%
      (11.5-35.2), and negative T waves in both precordial (V2-V6) and inferior leads
      of 30.2% (24.8-33.0) (P < 0.001). At multivariate analysis, the extent of
      negative T waves remained the only independent predictor of RV-EAS% area (B =
      4.4, 95%CI 1.3-7.4, P = 0.006) and correlated with the arrhythmic event-rate
      during follow-up (P = 0.03). CONCLUSIONS: In patients with ARVC, the extent of
      negative T-waves across 12-lead ECG allows noninvasive estimation of the amount
      of RV-EAS and prediction of EAS-related arrhythmic risk.

PMID- 24016195
TI  - Helical tomotherapy: an innovative radiotherapy technique for the treatment of
      locally advanced oropharynx and inoperable oral cavity carcinoma.
AB  - BACKGROUND: To report our initial clinical experience of helical tomotherapy (HT)
      in the treatment of locally advanced oropharynx and inoperable oral cavity
      cancer. METHODS: Between February 2008 and January 2011, 24 consecutive patients,
      15 with oropharyngeal cancer and 9 with oral cavity cancer were treated with
      exclusive radiotherapy or concomitant chemoradiotherapy. Simultaneous integrated
      boost (SIB) in 30 fractions scheme was prescribed to all patients, using Helical
      Tomotherapy. Doses administered to primary tumor, oropharynx/oral cavity and
      positive lymph-nodes and negative lymph-nodes were 66-67.5 Gy, 60-63 Gy and 54
      Gy, respectively. RESULTS: Complete response rate for the oropharynx and the oral
      cavity group was 86.7% and 77.8%, respectively. The 1 and 2-year Overall Survival
      (OS) and Disease Free Survival (DFS) rate for the oropharynx group was 92.9%,
      85.1%, 92.9% and 77.4% respectively. For the oral cavity group, 1 and 2-year OS
      and DFS rates were 55.6%, 55.6%, 75% and 75%, respectively. No patient developed
      grade >=3 mucositis, dysphagia or dermatitis. The maximum late-toxicity grade
      observed was 2, for all the variables examined. CONCLUSIONS: HT appears to
      achieve encouraging clinical outcomes in terms of response, survival and toxicity
      rates.

PMID- 24016196
TI  - Dynamical color-controllable lasing with extremely wide tuning range from red to
      green in a single alloy nanowire using nanoscale manipulation.
AB  - Multicolor lasing and dynamic color-tuning in a wide spectrum range are
      challenging to realize but critically important in many areas of technology and
      daily life, such as general lighting, display, multicolor detection, and
      multiband communication. By exploring nanoscale growth and manipulation, we have
      demonstrated the first active dynamical color control of multicolor lasing,
      continuously tunable between red and green colors separated by 107 nm in
      wavelength. This is achieved in a purposely engineered single CdSSe alloy
      nanowire with composition varied along the wire axis. By looping the wide-gap end
      of the alloy nanowire through nanoscale manipulation, two largely independent
      (only weakly coupled) laser cavities are formed respectively for the green and
      red color modes. Our approach simultaneously overcomes the two fundamental
      challenges for multicolor lasing in material growth and cavity design. Such
      multicolor lasing and continuous color tuning in a wide spectral range represents
      a new paradigm shift and would eventually enable color-by-design and white-color
      lasers for lighting, illumination, and many other applications. 

PMID- 24016197
TI  - Infrequent dialysis: a new paradigm for hemodialysis initiation.
AB  - Nearly a half-century ago, the thrice-weekly hemodialysis schedule was
      empirically established as a means to provide an adequate dialysis dose while
      also treating the greatest number of end-stage renal disease (ESRD) patients
      using limited resources. Landmark trials of hemodialysis adequacy have
      historically been anchored to thrice-weekly regimens, but a recent randomized
      controlled trial demonstrated that frequent hemodialysis (six times per week)
      confers cardiovascular and survival benefits. Based on these collective data and
      experience, clinical practice guidelines advise against a less than thrice-weekly
      treatment schedule in patients without residual renal function, yet provide
      limited guidance on the optimal treatment frequency when substantial native
      kidney function is present. Thus, during the transition from Stage 5 chronic
      kidney disease to ESRD, the current paradigm is to initiate hemodialysis on a
      "full-dose" thrice-weekly regimen even among patients with substantial residual
      renal function. However, emerging data suggest that frequent hemodialysis
      accelerates residual renal function decline, and infrequent regimens may provide
      better preservation of native kidney function. Given the high mortality rates
      during the first 6 months of hemodialysis and the survival benefits of preserved
      native kidney function, initiation with twice-weekly treatment schedules
      ("infrequent hemodialysis") with an incremental increase in frequency over time
      may provide an opportunity to optimize patient survival. This review outlines the
      clinical benefits of post-hemodialysis residual renal function, studies of twice
      weekly treatment regimens, and the potential risks and benefits of infrequent
      hemodialysis. 

PMID- 24016202
TI  - Protective role of 17-beta-estradiol towards IL-6 leukocyte expression induced by
      intense training in young female athletes.
AB  - Exercise performed at a competitive level could deeply modify the immune system
      and the cytokine response of athletes. In this report, we demonstrated that young
      elite female artistic gymnasts (n = 16; age: 9-15 years) showed an increase of
      interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) mRNA expression
      in blood mononuclear cells (PBMCs), in comparison to girls performing the same
      sport at a recreational level (n = 16; age: 10-15 years). The increase of IL-6
      and TNF-alpha mRNAs appeared to be directly linked to the intensity and duration
      of the training. Moreover, in elite athletes engaged in artistic gymnastics or in
      synchronised swimming (n =34; age: 9-15 years), IL-6 gene expression appeared to
      be modulated by the levels of circulating oestrogens: pre-pubertal athletes (n =
      20; age: 11 +/- 1 years) revealed a higher increase in IL-6 than pubertal
      athletes (n = 14; age: 14 +/- 1.6 years). In pre-pubertal athletes, body mass
      index (BMI) percentile was inversely correlated with the increase of both IL-6
      and TNF-alpha. The consequence of these events was the shift of the cytokine
      profile towards a pro-inflammatory status. These modifications, induced by
      training performed at an elite level, might negatively affect the growth of
      female children athletes.

PMID- 24016203
TI  - Obsessive passion: a dependency associated with injury-related risky behaviour in
      dancers.
AB  - Grounded in self-determination theory, obsessive passion for an activity has been
      associated with increased risky behaviour and rigid persistence, both symptomatic
      of dependence. However, it is unknown whether obsessive passion may predict the
      development of dependence, and furthermore, theoretically important relationships
      between basic need satisfaction, passion, exercise dependence and subsequent
      risky behaviour have not been fully explored. A sample of 100 professional
      dancers (50(fs); 50(ms); Mage = 20.88; SD = 2.69) completed self-ratings of risk
      related behaviours (doctor visits; following treatment, and warming up), passion
      for dance and dance dependence. Findings supported the maladaptive nature of
      obsessive passion in relation to risky behaviour and as predicted dance
      dependence mediated this relationship. Interestingly, need satisfaction was
      positively related to both obsessive passion and harmonious passion. Results are
      discussed in the light of self-determination theory and dysfunctions of obsessive
      passion, suggesting that professional dancers are at risk of employing
      maladaptive behaviours if high in obsessive passion, which may be detectable via
      symptoms of dance dependence.

PMID- 24016201
TI  - Cortical potentials in an auditory oddball task reflect individual differences in
      working memory capacity.
AB  - This study determined whether auditory cortical responses associated with
      mechanisms of attention vary with individual differences in working memory
      capacity (WMC) and perceptual load. The operation span test defined subjects with
      low versus high WMC, who then discriminated target/nontarget tones while EEG was
      recorded. Infrequent white noise distracters were presented at midline or +/-90
      degrees  locations, and perceptual load was manipulated by varying nontarget
      frequency. Amplitude of the N100 to distracters was negatively correlated with
      WMC. Relative to targets, only high WMC subjects showed attenuated N100
      amplitudes to nontargets. In the higher WMC group, increased perceptual load was
      associated with decreased P3a amplitudes to distracters and longer-lasting
      negative slow wave to nontargets. Results show that auditory cortical processing
      is associated with multiple facets of attention related to WMC and possibly
      higher-level cognition. 

PMID- 24016204
TI  - Surveillance and control of rabies in La Reunion, Mayotte, and Madagascar.
AB  - Mayotte and La Reunion islands are currently free of animal rabies and
      surveillance is performed by the French Human and Veterinary Public Health
      Services. However, dog rabies is still enzootic in Madagascar with 4 to 10
      confirmed human cases each year. The number of antirabies medical centres in
      Madagascar is still scarce to provide easy access to the local population for
      post-exposure rabies prophylaxis. Furthermore, stray dog populations are
      considerable and attempts to control rabies by mass campaigns of dog vaccination
      have not received sufficient attention from the national health authorities. To
      address these challenges, an expanded program to control rabies needs to be
      initiated by the Malagasy authorities. 

PMID- 24016205
TI  - Personality and adaptive performance at work: a meta-analytic investigation.
AB  - We examined emotional stability, ambition (an aspect of extraversion), and
      openness as predictors of adaptive performance at work, based on the evolutionary
      relevance of these traits to human adaptation to novel environments. A meta
      analysis on 71 independent samples (N = 7,535) demonstrated that emotional
      stability and ambition are both related to overall adaptive performance.
      Openness, however, does not contribute to the prediction of adaptive performance.
      Analysis of predictor importance suggests that ambition is the most important
      predictor for proactive forms of adaptive performance, whereas emotional
      stability is the most important predictor for reactive forms of adaptive
      performance. Job level (managers vs. employees) moderates the effects of
      personality traits: Ambition and emotional stability exert stronger effects on
      adaptive performance for managers as compared to employees.

PMID- 24016206
TI  - Hierarchical representations of the five-factor model of personality in
      predicting job performance: integrating three organizing frameworks with two
      theoretical perspectives.
AB  - Integrating 2 theoretical perspectives on predictor-criterion relationships, the
      present study developed and tested a hierarchical framework in which each five
      factor model (FFM) personality trait comprises 2 DeYoung, Quilty, and Peterson
      (2007) facets, which in turn comprise 6 Costa and McCrae (1992) NEO facets. Both
      theoretical perspectives-the bandwidth-fidelity dilemma and construct
      correspondence-suggest that lower order traits would better predict facets of job
      performance (task performance and contextual performance). They differ, however,
      as to the relative merits of broad and narrow traits in predicting a broad
      criterion (overall job performance). We first meta-analyzed the relationship of
      the 30 NEO facets to overall job performance and its facets. Overall, 1,176
      correlations from 410 independent samples (combined N = 406,029) were coded and
      meta-analyzed. We then formed the 10 DeYoung et al. facets from the NEO facets,
      and 5 broad traits from those facets. Overall, results provided support for the 6
      2-1 framework in general and the importance of the NEO facets in particular.

PMID- 24016207
TI  - Exploring the disruptive effects of psychopathy and aggression on group processes
      and group effectiveness.
AB  - The present research examines the influence of implicit and explicit personality
      characteristics on group process and effectiveness. Individuals from 112 groups
      participated in 2 problem-solving tasks and completed measures of group process
      and effectiveness. Results indicated that groups characterized by higher levels
      of psychopathy and implicit aggression tended to have more dysfunctional
      interactions and negative perceptions of the group. In addition, task
      participation and negative socioemotional behaviors fully mediated the
      relationship between group personality traits and group commitment and cohesion,
      and negative socioemotional behaviors fully mediated the relationship between
      group personality and performance on both tasks. Implications of antisocial
      traits for group interactions and performance, as well as for future theory and
      research, are discussed.

PMID- 24016208
TI  - Photoreduction of CO2 using [Ru(bpy)2(CO)L]n+ catalysts in biphasic
      solution/supercritical CO2 systems.
AB  - The reduction of CO2 in a biphasic liquid-condensed gas system was investigated
      as a function of the CO2 pressure. Using 1-benzyl-1,4-dihydronicotinamide (BNAH)
      as sacrificial electron donor dissolved in a dimethylformamide-water mixture and
      [Ru(bpy)2(CO)L](n+) as a catalyst and [Ru(bpy)3](2+) as a photosensitizer, the
      reaction was found to produce a mixture of CO and formate, in total about 250
      MUmol after just 2 h. As CO2 pressure increases, CO formation is greatly favored,
      being four times greater than that of formate in aqueous systems. In contrast,
      formate production was independent of CO2 pressure, present at about 50 MUmol.
      Using TEOA as a solvent instead of water created a single-phase supercritical
      system and greatly favored formate synthesis, but similarly increasing CO2
      concentration favored the CO catalytic cycle. Under optimum conditions, a
      turnover number (TON) of 125 was obtained. Further investigations of the
      component limits led to an unprecedented TON of over 1000, and an initial
      turnover frequency (TOF) of 1600 h(-1). 

PMID- 24016209
TI  - Levomilnacipran for major depressive disorder: a systematic review of the
      efficacy and safety profile for this newly approved antidepressant--what is the
      number needed to treat, number needed to harm and likelihood to be helped or
      harmed?
AB  - OBJECTIVE: To describe the efficacy and safety of levomilnacipran (extended
      release capsules) for the treatment of major depressive disorder (MDD). DATA
      SOURCES: The pivotal registration trials were accessed by querying
      http://www.ncbi.nlm.nih.gov/pubmed/, http://www.clinicaltrialsregister.eu and
      http://www.clinicaltrials.gov for the search terms 'levomilnacipran' and 'F2695',
      and by obtaining posters presented at congresses. Product labelling provided
      additional information. STUDY SELECTION: All available clinical reports of
      studies were identified. DATA EXTRACTION: Descriptions of the principal results
      and calculation of number needed to treat (NNT) and number needed to harm (NNH)
      for relevant dichotomous outcomes were extracted from the available study reports
      and other sources of information. DATA SYNTHESIS: Levomilnacipran (1S, 2R
      milnacipran) is a potent and selective serotonin-norepinephrine reuptake
      inhibitor with greater potency for inhibition of norepinephrine relative to
      serotonin reuptake. Approval for the treatment of MDD was based on a clinical
      development program that included one 10-week Phase II and four 8-week Phase III
      randomised placebo-controlled clinical trials in outpatients with MDD where
      levomilnacipran was titrated to target doses ranging from 40 to 120 mg taken once
      daily. Four of the five trials demonstrated efficacy as measured by the
      Montgomery Asberg Depression Rating Scale, with a NNT for response vs. placebo of
      9 (95% CI 7-15), and for remission, 14 (95% CI 10-28). Levomilnacipran also
      demonstrated superiority over placebo as measured by improvement in the Sheehan
      Disability Scale functional impairment total score. NNH vs. placebo for
      discontinuation because an adverse event (AE) across all five trials was 19 (95%
      CI 14-28). The most commonly encountered AEs (incidence >= 5% and at least twice
      the rate of placebo) as identified in product labelling were nausea,
      hyperhidrosis, constipation, heart rate increased, erectile dysfunction in men,
      vomiting, tachycardia and palpitations, with NNH values vs. placebo of 10 (95% CI
      8-12), 15 (95% CI 12-19), 17 (95% CI 13-24), 21 (95% CI 17-29), 20 (95% CI 14
      36), 25 (95% CI 20-37), 25 (95% CI 19-40) and 30 (95% CI 22-49), respectively.
      Levomilnacipran was not associated with clinically relevant weight change in the
      short-term trials or in a 48-week open-label extension trial. Mean changes from
      baseline in systolic blood pressure (BP), diastolic BP and heart rate were +3.0
      mmHg, +3.2 mm Hg and +7.4 bpm for levomilnacipran, and -0.4 mmHg, no change and 
      0.3 bpm for placebo, respectively. Categorical shift in BP from normal or
      prehypertension at baseline to stage 1 or stage 2 hypertension at end of study
      was 10.4% for levomilnacipran vs. 7.1% for placebo, for a NNH of 31 (95% CI 18
      94). CONCLUSIONS: Levomilnacipran represents another option for the treatment of
      MDD. Levomilnacipran appears to have a favourable weight-gain profile. Additional
      controlled data regarding long-term efficacy and comparative effectiveness will
      help characterise this new agent.

PMID- 24016210
TI  - Why do nurses intend to leave their organization? A large-scale analysis in long
      term care.
AB  - AIM: To analyse the impact of six job characteristics on the intention of nurses
      to leave their organization, specifically focusing on long-term care settings:
      nursing homes, care homes and home care. BACKGROUND: When nurses leave their
      organization, this can negatively affect organizational performance.
      Organizations have to recruit new nurses and tacit knowledge is lost.
      Furthermore, organizational turnover could contribute to the nursing shortage,
      which will increasingly become a problem given the ageing population. This
      article adds to the literature, given: (a) its focus on long-term care; and (b)
      by explicating the differences between nursing and care homes (intramural) on one
      hand and home care (extramural) on the other. DESIGN: Survey. METHOD: Survey of
      9982 nurses in 156 Dutch organizations in 2010-2011, 6321 nurses in nursing and
      care homes and 3661 nurses working in home care, based on the ActiZ Benchmark in
      Healthcare. RESULTS: First, the most important reason for nurses' intention to
      leave is insufficient development and career opportunities. Secondly, a negative
      working atmosphere strongly influenced intention to leave. The impact of the
      working atmosphere is not often examined in the literature. However, this
      research shows that it is an important reason. Thirdly, intention to leave is
      partly context dependent. More specifically, when nurses in home care felt that
      their autonomy was reduced, this strongly influenced their intention to leave,
      although this was not the case for nurses working in nursing and care homes.
      CONCLUSION: This article provides guidelines for organizations on how to retain
      their nurses.

PMID- 24016211
TI  - Engineered botulinum neurotoxins as new therapeutics.
AB  - Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inhibiting
      neurotransmission at cholinergic nerve terminals. Each BoNT consists of three
      domains that are essential for toxicity: the binding domain, the translocation
      domain, and the catalytic light-chain domain. BoNT modular architecture is
      associated with a multistep mechanism that culminates in the intracellular
      proteolysis of SNARE (soluble N-ethylmaleimide-sensitive-fusion-protein
      attachment protein receptor) proteins, which prevents synaptic vesicle
      exocytosis. As the most toxic proteins known, BoNTs have been extensively studied
      and are used as pharmaceutical agents to treat an increasing variety of
      disorders. This review summarizes the level of sophistication reached in BoNT
      engineering and highlights the diversity of approaches taken to utilize the
      modularity of the toxin. Improved efficiency and applicability have been achieved
      by direct mutagenesis and interserotype domain rearrangement. The scope of BoNT
      activity has been extended to nonneuronal cells and offers the basis for novel
      biomolecules in the treatment of secretion disorders.

PMID- 24016212
TI  - The druggable genome: Evaluation of drug targets in clinical trials suggests
      major shifts in molecular class and indication.
AB  - The largest innovations within pharmaceutical development come through new
      compounds that have unique and novel modes of action. These innovations commonly
      involve expanding the protein space targeted by pharmaceutical agents. At
      present, information about drugs and drug targets is available online via public
      databases such as DrugBank and the Therapeutic Targets Database. However, this
      information is biased, understandably so, toward established drugs and drug
      target interactions. To gain a better overview of the drug-targeted portion of
      the human proteome and the directions of current drug development, we developed a
      data set of clinical trial drug-target interactions based on CenterWatch's Drugs
      in Clinical Trials Database, one of the largest databases of its kind. Our
      curation identified 475 potentially novel clinical trial drug targets. This
      review aims to identify trends in drug development based on the potentially novel
      targets currently being explored in clinical trials.

PMID- 24016213
TI  - Body size and sexual size dimorphism in primates: influence of climate and net
      primary productivity.
AB  - Understanding the evolution of body size and sexual size dimorphism has been a
      longstanding goal in evolutionary biology. Previous work has shown that
      environmental stress can constrain male-biased sexual size dimorphism at the
      population level, but we know little about how this might translate to
      geographical patterns of body size and sexual size dimorphism at the species
      level. Environmental constraints due to a highly seasonal, resource-poor and/or
      variable environment have often been cited to explain the unusual lack of sexual
      size dimorphism among Madagascar's diverse and numerous primate taxa; however,
      empirical tests of this hypothesis are lacking. Using a phylogenetic approach and
      a geographical information system platform, we explored the role of seasonality,
      interannual variability and annual measures of temperature and rainfall, and net
      primary productivity on patterns of body size and sexual size dimorphism across
      130 species of primates. Phylogenetically controlled comparisons showed no
      support for a role of environmental constraints in moderating sexual size
      dimorphism at the interspecific level, despite significant associations of
      environmental variables with body mass. Results suggest that the focus of
      discussions that have dominated in the last two decades regarding the role of
      environmental constraints in driving patterns of monomorphism of Madagascar's
      lemurs should be reconsidered; however, the conundrum remains. 

PMID- 24016214
TI  - Electrochemistry and Spectroelectrochemistry of europium(III) chloride in 3LiCl
      2KCl from 643 to 1123 K.
AB  - The electrochemical and spectroelectrochemical behavior of europium(III) chloride
      in a molten salt eutectic, 3LiCl-2KCl, over a temperature range of 643-1123 K
      using differential pulse voltammetry, cyclic voltammetry, potential step
      chronoabsorptometry, and thin-layer spectroelectrochemistry is reported. The
      electrochemical reaction was determined to be the one-electron reduction of
      Eu(3+) to Eu(2+) at all temperatures. The redox potential of Eu(3+/2+) shifts to
      more positive potentials, and the diffusion coefficient for Eu(3+) increases as
      temperature increases. The results for the number of electrons transferred, redox
      potential, and diffusion coefficient are in good agreement between the
      electrochemical and spectroelectrochemical techniques. This research extends our
      ability to develop a spectroelectrochemical sensor for lanthanides and actinides
      into molten salt media. 

PMID- 24016215
TI  - Proteomic revolution to improve tools for evaluating male fertility in animals.
AB  - Artificial insemination has been used as a common breeding technique for the
      rapid dissemination of important genes to improve livestock quality. However,
      infertility or subfertility in the male leads to the disintegration of the
      breeding system and large economic losses. Therefore, the development of an
      accurate diagnostic protocol for male fertility is of critical importance. To
      this end, many basic laboratory assays have been developed on the basis of semen
      analysis. Although these assays may provide a preliminary estimate of male
      fertility, their accuracies are often unacceptably low. Therefore, it is vital to
      develop new semen analyses that are simple to use and accurate. Proteomic
      approaches will shed light on understanding sperm physiology and help in
      developing new diagnostic tools for male fertility. The aim of this study was to
      review the retrospective semen analyses and prospective proteomic studies of male
      fertility determination and usefulness of proteomic approaches in diagnosing male
      fertility potential in animal industry. 

PMID- 24016216
TI  - Local and global processing in blind and sighted children in a naming and drawing
      task.
AB  - This study investigated the spatial analysis of tactile hierarchical patterns in
      110 early-blind children aged 6-8 to 16-18 years, as compared to 90 blindfolded
      sighted children, in a naming and haptic drawing task. The results revealed that
      regardless of visual status, young children predominantly produced local
      responses in both tasks, whereas the production of integrated responses emerged
      later. Development of local and global processing seems to proceed similarly in
      the two populations, but local processing continued to occur at high levels over
      a larger age range in the blind. The possibility of visual mediation is pointed
      out, as totally blind children tended to process information locally more often
      than blind children with minimal light perception.

PMID- 24016217
TI  - Nanotechnology in plant disease management: DNA-directed silver nanoparticles on
      graphene oxide as an antibacterial against Xanthomonas perforans.
AB  - Bacterial spot caused by Xanthomonas perforans is a major disease of tomatoes,
      leading to reduction in production by 10-50%. While copper (Cu)-based
      bactericides have been used for disease management, most of the X. perforans
      strains isolated from tomatoes in Florida and other locations worldwide are Cu
      resistant. We have developed DNA-directed silver (Ag) nanoparticles (NPs) grown
      on graphene oxide (GO). These Ag@dsDNA@GO composites effectively decrease X.
      perforans cell viability in culture and on plants. At the very low concentration
      of 16 ppm of Ag@dsDNA@GO, composites show excellent antibacterial capability in
      culture with significant advantages in improved stability, enhanced antibacterial
      activity, and stronger adsorption properties. Application of Ag@dsDNA@GO at 100
      ppm on tomato transplants in a greenhouse experiment significantly reduced the
      severity of bacterial spot disease compared to untreated plants, giving results
      similar to those of the current grower standard treatment, with no phytotoxicity.

PMID- 24016219
TI  - Early cerebral infarction following aneurysmal subarachnoid hemorrhage:
      frequency, risk factors, patterns, and prognosis.
AB  - Early cerebral infarction (ECI) following aneurysmal subarachnoid hemorrhage
      (aSAH) remains poorly understood. This study aims to determine the frequency and
      risk factors of this special episode, as well as to assess the relationship
      between its patterns and outcome. We retrospectively enrolled 243 patients who
      underwent aneurysm treatment within 60 hours of SAH. ECI was defined as one or
      more new hypodense abnormalities on computed tomography within 3 days after SAH,
      rather than lesions attributable to edema, retraction effect, and ventricular
      drain placement. Risk factors were tested by multivariate analysis. The infarct
      was classified by an established grading system (single or multiple, cortical or
      deep or combined). Poor outcome was defined as the Glasgow Outcome Score of
      severe disability or worse. Sixty-five patients (26.7%) had early infarction.
      Acute hydrocephalus (odds ratio [OR] 6.67; 95% confidence interval [CI] 1.59
      27.95), admission plasma glucose level (OR 1.42 per mmol/L; 95% CI 1.16-1.73),
      and treatment modality (OR 16.27; 95% CI 4.05-65.28) were independent predictors
      of ECI. The pattern was single cortical in 19 patients (29.2%), single deep in 9
      (13.8%), multiple cortical in 8 (12.3%), multiple deep in 14 (21.5%), and
      multiple combined in 15 (23.1%). ECI was associated with delayed cerebral
      infarction (DCI) (P = 0.002) and poor outcome (P < 0.001). Multiple combined
      infarction was related to poor outcome (P = 0.001). In summary, the occurrence of
      ECI, which is associated with surgical treatment, acute hydrocephalus and high
      admission plasma glucose, may potentially predict DCI and unfavorable outcome.
      Further studies are warranted to reveal the underlying mechanisms of this event
      and thereby minimize it. 

PMID- 24016218
TI  - Effectiveness of the National Program of Complementary Feeding for older adults
      in Chile on vitamin B12 status in older adults; secondary outcome analysis from
      the CENEX Study (ISRCTN48153354).
AB  - BACKGROUND: Older people are at increased risk of vitamin B12 deficiency and the
      provision of fortified foods may be an effective way to ensure good vitamin B12
      status in later life. AIM: To evaluate the effectiveness of a vitamin B12
      fortified food provided by a national program of complementary food for older
      people on plasma vitamin B12 levels. SUBJECTS AND METHODS: A random sub-sample of
      351 subjects aged 65-67 y from a large cluster randomised controlled trial
      provided blood samples at baseline and after 24 months of intervention. The
      intervention arm (10 clusters 186 participants) received a vitamin B12 fortified
      food designed to deliver 1.4 MUg/day, while the control arm did not receive
      complementary food (10 clusters, 165 participants). Serum vitamin B12 and folate
      levels determined by radioimmunoassay were used to estimate the effect of
      intervention on vitamin B12 levels, adjusting for baseline levels and sex.
      RESULTS: Attrition at 24 months was 16.7% and 23.6% in the intervention and
      control arms respectively (p = 0.07). Over 24 months of intervention, mean (95%
      CI) serum vitamin B12 decreased from 392 (359-425) pmol/dL to 357 (300-414)
      pmol/dL (p < 0.07) in the intervention arm and from 395 (350-440) pmol/dL to 351
      (308-395) pmol/dL in the control arm. There was no significant effect of the
      intervention on folate status. DISCUSSION: Our findings suggest that foods
      fortified with 1.4 MUg/daily vitamin B12 as provided by Chile's national
      programme for older people are insufficient to ensure adequate vitamin B12 levels
      in this population. Chile has a long and successful experience with nutrition
      intervention programs; however, the country's changing demographic and
      nutritional profiles require a constant adjustment of the programs.

PMID- 24016220
TI  - Three new phenanthrenes, a new stilbenoid isolated from the roots of Stemona
      tuberosa Lour. and their cytotoxicity.
AB  - Three new phenanthrenes, stemophenanthrenes A-C (1-3), along with one new
      stilbenoid, isopinosylvin A (4) and a known compound methyl ferulate (5), were
      isolated and identified from the roots of Stemona tuberosa Lour. plants,
      collected in Attapu province (Laos). Their structures were elucidated by
      spectroscopic analysis (FT-ICR-MS, IR, UV, 1D and 2D NMR). These compounds show
      moderate cytotoxic activity against four cancer cell lines, KB (a human epidermal
      carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and
      HepG2 (hepatocellular carcinoma). 

PMID- 24016221
TI  - Relationship between estimated glomerular filtration rate, albuminuria, and
      oxidant status in the Japanese population.
AB  - BACKGROUND: In the general population, reported levels of oxidative stress and
      antioxidant potential seem to vary. The aim of this study was to investigate the
      levels of oxidant status markers in relation to estimated glomerular filtration
      rate (eGFR) and albuminuria in Japanese population. METHODS: Data were analyzed
      from 8335 individuals who underwent a general health screening test. For the
      estimation of albuminuria, urinary albumin-to-creatinine ratio (UAER) was
      calculated. Oxidant status was determined by assessing derivatives of reactive
      oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). RESULTS:
      After adjusting for age, high blood pressure, depressor agent use, CRP, smoking
      status, multivariate logistic regression analysis showed that the lowest eGFR
      quartile was associated negatively with the top d-ROM quartile in men (odds ratio
      0.78 [95% CI 0.62-0.98, P = 0.034]) and the highest UAER was associated with the
      top d-ROM in men (odds ratio 1.68) [95% CI 1.35-2.10, P < 0.001]. In addition,
      both the first eGFR quartile and the fourth UAER quartile showed significant
      positive association with low BAP levels in men, but not in women. CONCLUSIONS:
      Among men who underwent general health screening, lower eGFR and increased
      albuminuria was negatively and positively, respectively, associated with higher
      oxidative stress levels, whereas both conditions were positively associated with
      lower antioxidant potential levels.

PMID- 24016223
TI  - Cryoablation versus RF ablation for AVNRT: A meta-analysis and systematic review.
AB  - INTRODUCTION: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most
      common supraventricular tachycardia referred for ablation. High success rates
      have been accompanied with a small risk of atrioventricular (AV) block.
      Cryoablation has been used as an alternative to radiofrequency (RF) ablation, but
      studies have been underpowered in comparing the 2 techniques. METHODS AND
      RESULTS: An electronic search and hand-search of reference lists for published
      and unpublished data was carried out. Comparative studies (cohort and randomized
      controlled trials) of RF versus cryoablation for AVNRT were identified
      independently by 2 reviewers. Searches were limited to English language human
      studies. The primary metameter was long-term AVNRT recurrence (>2 months
      postprocedure and ECG/electrophysiology study [EPS]-documented) and secondary
      metameters included acute procedural failure and AV block requiring pacing. A
      total of 5,617 patients in 14 trials were included in this systematic review.
      Acute procedural failure with cryoablation was slightly higher than with RF
      ablation, but the difference was not statistically significant (risk ratio [RR]
      1.44 [95% confidence interval; CI 0.91-2.28], P = 0.12). Long-term recurrence was
      higher with cryoablation (RR 3.66 [95% CI 1.84-7.28], P = 0.0002) even after
      adjusting for larger (6 mm) cryocatheter tips, "insurance lesions" and longer (>6
      months) follow-up duration. RF ablation for AVNRT was associated with permanent
      AV block in 0.75% of patients, but was not reported in any patients treated with
      cryoablation (n = 1066, P = 0.01). CONCLUSIONS: Cryoablation is a safe and
      effective treatment for AVNRT. Although late-recurrence is more common with
      cryoablation than with RF ablation, avoidance of permanent AVN block makes it an
      attractive option in patients where the avoidance of AV block assumes higher
      priority (such as children and young adults).

PMID- 24016222
TI  - Measurements of parity-violating asymmetries in electron-deuteron scattering in
      the nucleon resonance region.
AB  - We report on parity-violating asymmetries in the nucleon resonance region
      measured using inclusive inelastic scattering of 5-6 GeV longitudinally polarized
      electrons off an unpolarized deuterium target. These results are the first parity
      violating asymmetry data in the resonance region beyond the Delta(1232). They
      provide a verification of quark-hadron duality-the equivalence of the quark- and
      hadron-based pictures of the nucleon-at the (10-15)% level in this electroweak
      observable, which is dominated by contributions from the nucleon electroweak
      gammaZ interference structure functions. In addition, the results provide
      constraints on nucleon resonance models relevant for calculating background
      corrections to elastic parity-violating electron scattering measurements.

PMID- 24016224
TI  - Nanoparticles in a capillary trap: dynamic self-assembly at fluid interfaces.
AB  - Dynamic self-assembly is an emerging scientific concept aimed to construct
      artificial systems of adaptative behavior. Here, we present a first nanoscopic
      system that is able to dynamically self-assemble in two dimensions. This system
      is composed of charged gold nanoparticles, dispersed at the air-water interface,
      which self-assemble into a dense monolayer of area of several square centimeters
      in response to surface tension gradient. The surface tension gradient is imposed
      by localized addition or removal of organic solvent from the interface. After the
      surface tension is equalized over the whole fluid interface, the nanoparticles
      return to their initial dispersed state. The arrangement of nanoparticles before
      and after the self-assembly was characterized using SEM microscopy and SAXS
      spectroscopy. The constructed self-assembling system offers a "chemical"
      alternative for the Langmuir-Blodgett technique. Also, it was applied for
      creating self-erasing nanoparticle patterns on a fluid surface. 

PMID- 24016226
TI  - Giant piezoresistive on/off ratios in rare-earth chalcogenide thin films enabling
      nanomechanical switching.
AB  - Sophisticated microelectromechanical systems for device and sensor applications
      have flourished in the past decade. These devices exploit piezoelectric,
      capacitive, and piezoresistive effects, and coupling between them. However, high
      performance piezoresistivity (as defined by on/off ratio) has primarily been
      observed in macroscopic single crystals. In this Letter, we show for the first
      time that rare-earth monochalcogenides in thin film form can modulate a current
      by more than 1000 times due to a pressure-induced insulator to metal transition.
      Furthermore, films as thin as 8 nm show a piezoresistive response. The
      combination of high performance and scalability make these promising candidates
      for nanoscale applications, such as the recently proposed piezoelectronic
      transistor (PET). The PET would mechanically couple a piezoelectric thin film
      with a piezoresistive switching layer, potentially scaling to higher speeds and
      lower powers than today's complementary metal-oxide-semiconductor technology.

PMID- 24016225
TI  - Residential culturable fungi, (1-3, 1-6)-beta-d-glucan, and ergosterol
      concentrations in dust are not associated with asthma, rhinitis, or eczema
      diagnoses in children.
AB  - Qualitative reporting of home indoor moisture problems predicts respiratory
      diseases. However, causal agents underlying such qualitative markers remain
      unknown. In the homes of 198 multiple allergic case children and 202 controls in
      Sweden, we cultivated culturable fungi by directly plating dust, and quantified
      (1-3, 1-6)-beta-D-glucan and ergosterol in dust samples from the child's bedroom.
      We examined the relationship between these fungal agents and degree of parent or
      inspector-reported home indoor dampness, and microbiological laboratory's mold
      index. We also compared the concentrations of these agents between multiple
      allergic cases and healthy controls, as well as IgE-sensitization among cases.
      The concentrations of culturable fungal agents were comparable between houses
      with parent and inspector-reported mold issues and those without. There were no
      differences in concentrations of the individual or the total summed culturable
      fungi, (1-3, 1-6)-beta-D-glucan, and ergosterol between the controls and the
      multiple allergic case children, or individual diagnosis of asthma, rhinitis, or
      eczema. Culturable fungi, (1-3, 1-6)-beta-D-glucan, and ergosterol in dust were
      not associated with qualitative markers of indoor dampness or mold or indoor
      humidity. Furthermore, these agents in dust samples were not associated with any
      health outcomes in the children.

PMID- 24016228
TI  - Seasonal variations in physical fitness among elementary school children.
AB  - There is empirical evidence that children's physical activity is dependent on
      climatic conditions. In addition, a correlation between physical activity level
      and physical fitness has been identified. In this longitudinal study, we
      investigate whether seasons have an influence on physical fitness. A total of 145
      German elementary school children were tested every six months over a two-year
      period. We used the German Motor Test 6-18 to assess physical fitness.
      Performance in the 6-min endurance run (P < 0.001), bidirectional jumping (P <
      0.001), the standing long jump (P = 0.026), the 20 m sprint (P = 0.006) and the
      stand-and-reach task (P = 0.017) was significantly better in summer than in
      winter. There were no differences in the ability to balance backwards (P =
      0.120); in the winter, the results for push-ups (P < 0.001) and sit-ups (P <
      0.001) were better than those in the summer. We have shown that physical fitness
      is significantly influenced by the season. Consequently, when children's fitness
      tests are used (e.g. as the basis for intervention programs, for classifying
      health-risk groups or for recognising talent), the season in which testing
      occurred should be reported and accounted for in future studies.

PMID- 24016227
TI  - Outcomes and complication rates of different bone grafting modalities in long
      bone fracture nonunions: a retrospective cohort study in 182 patients.
AB  - BACKGROUND: Novel bone substitutes have challenged the notion of autologous bone
      grafting as the 'gold standard' for the surgical treatment of fracture nonunions.
      The present study was designed to test the hypothesis that autologous bone
      grafting is equivalent to other bone grafting modalities in the management of
      fracture nonunions of the long bones. METHODS: A retrospective review of patients
      with fracture nonunions included in two prospective databases was performed at
      two US level 1 trauma centers from January 1, 1998 (center 1) or January 1, 2004
      (center 2), respectively, until December 31, 2010 (n = 574). Of these, 182
      patients required adjunctive bone grafting and were stratified into the following
      cohorts: autograft (n = 105), allograft (n = 38), allograft and autograft
      combined (n = 16), and recombinant human bone morphogenetic protein-2 (rhBMP-2)
      with or without adjunctive bone grafting (n = 23). The primary outcome parameter
      was time to union. Secondary outcome parameters consisted of complication rates
      and the rate of revision procedures and revision bone grafting. RESULTS: The
      autograft cohort had a statistically significant shorter time to union (198 +/-
      172-225 days) compared to allograft (416 +/- 290-543 days) and exhibited a trend
      towards earlier union when compared to allograft/autograft combined (389 +/- 159
      619 days) or rhBMP-2 (217 +/- 158-277 days). Furthermore, the autograft cohort
      had the lowest rate of surgical revisions (17%) and revision bone grafting (9%),
      compared to allograft (47% and 32%), allograft/autograft combined (25% and 31%),
      or rhBMP-2 (27% and 17%). The overall new-onset postoperative infection rate was
      significantly lower in the autograft group (12.4%), compared to the allograft
      cohort (26.3%) (P < 0.05). CONCLUSION: Autologous bone grafting appears to
      represent the bone grafting modality of choice with regard to safety and
      efficiency in the surgical management of long bone fracture nonunions.

PMID- 24016229
TI  - Impact of acid and alkaline pretreatments on the molecular network of wheat
      gluten and on the mechanical properties of compression-molded glassy wheat gluten
      bioplastics.
AB  - Wheat gluten can be converted into rigid biobased materials by high-temperature
      compression molding at low moisture contents. During molding, a cross-linked
      protein network is formed. This study investigated the effect of mixing gluten
      with acid/alkali in 70% ethanol at ambient temperature for 16 h followed by
      ethanol removal, freeze-drying, and compression molding at 130 and 150  degrees C
      on network formation and on types of cross-links formed. Alkaline pretreatment (0
      100 mmol/L sodium hydroxide or 25 mmol/L potassium hydroxide) strongly affected
      gluten cross-linking, whereas acid pretreatment (0-25 mmol/L sulfuric acid or 25
      mmol/L hydrochloric acid) had limited effect on the gluten network. Molded
      alkaline-treated gluten showed enhanced cross-linking but also degradation when
      treated with high alkali concentrations, whereas acid treatment reduced gluten
      cross-linking. beta-Elimination of cystine and lanthionine formation occurred
      more pronouncedly at higher alkali concentrations. In contrast, formation of
      disulfide and nondisulfide cross-links during molding was hindered in acid
      pretreated gluten. Bioplastic strength was higher for alkali than for acid
      pretreated samples, whereas the flexural modulus was only slightly affected by
      either alkaline or acid pretreatment. Apparently, the ratio of disulfide to
      nondisulfide cross-links did not affect the mechanical properties of rigid gluten
      materials. 

PMID- 24016230
TI  - Elucidating the etiology of individual differences in parenting: A meta-analysis
      of behavioral genetic research.
AB  - Decades of research have indicated the foundational importance of parenting to
      offspring outcomes during childhood and beyond. Unearthing the specific origins
      of parenting is therefore a critically important research objective. Extant
      research on this topic has suggested that parenting behaviors are multidetermined
      (Belsky, 1984) and are associated with a wide range of contextual and familial
      characteristics (e.g., ethnicity, community, family financial stress), as well as
      characteristics of the parents (e.g., personality) and their children (e.g.,
      temperament). Behavioral genetic studies have further indicated that parenting
      behaviors are in fact heritable-that is, individual differences in parenting are
      at least partially a function of genetic differences between persons. Critically,
      however, the estimates of these genetic influences have varied dramatically
      across studies. It is also unclear how factors such as parent gender, child age,
      and methodological considerations may impact genetic influences on parenting
      behavior. In the current set of meta-analyses, we sought to quantitatively
      synthesize twin and adoption studies (n = 56) examining the etiology of parenting
      behavior, with the goal of more definitively cataloguing genetic and
      environmental effects on parenting. Results reveal significant effects of
      parental genetic makeup on parental behavior, but also highlight the genetic
      makeup of the child as a particularly prominent source of genetic transmission
      (via evocative gene-environment correlation). Environmental contributions to
      parenting also emerged as important, including both shared and nonshared
      environmental effects. Theoretical implications of these findings are discussed.

PMID- 24016231
TI  - Evolution of the strongest vertebrate rightward action asymmetries: Marine mammal
      sidedness and human handedness.
AB  - Marine mammals and humans have the strongest manifestations of what is apparently
      a vertebrate-wide tendency toward a rightward action asymmetry associated with
      routine behavior. Marine mammal asymmetries usually involve whole-body actions
      associated with feeding. The human-like strength of these asymmetries may result
      from a problem of external aquatic support for the reactive component of the
      demanding lateral maneuvers of large marine mammals in daily pursuit of prey. Our
      asymmetrical primate heritage may also have begun with a rightward whole-body
      asymmetry, in prosimians, perhaps also resulting from problems of support for the
      reactive component of action; in this case arising from the arboreal habitat (and
      paradoxically including left-handedness). Monkeys and apes (simians) subsequently
      added right-sided adaptations for manipulation, bimanual coordination,
      bipedalism, throwing, and manual communication, most importantly by distal
      elaboration of limb function. The strength of human right-handedness may result
      partly from further elaboration of these simian action adaptations and partly
      from an evolving cognitive superstructure for tool use and language.

PMID- 24016232
TI  - Does the interpersonally sensitive disposition advance research on personality
      and health? Comment on Marin and Miller (2013).
AB  - Marin and Miller (2013) have proposed the interpersonally sensitive disposition
      as an integrative model of personality characteristics affecting physical health.
      The model has considerable heuristic value and applied potential, and the related
      research is discussed with thoughtful attention to long-standing challenges and
      limitations in research on personality and health. However, their conclusions
      about the association of interpersonal sensitivity and subsequent health may be
      premature and overstated. The agenda for future research they propose is
      valuable, and in addition to the important epidemiologic and psychobiologic
      studies they describe, the essential research on the measurement of interpersonal
      sensitivity and its association with other personality and social-environmental
      risk factors will be best advanced through application of concepts and methods in
      current personality science and related interpersonal approaches.

PMID- 24016233
TI  - Interpersonal sensitivity, social inhibition, and type D personality: how and
      when are they associated with health? Comment on Marin and Miller (2013).
AB  - Marin and Miller (2013) proposed interpersonal sensitivity (IS), characterized by
      ongoing concerns about social threats, as a new model to integrate research on
      interpersonal traits and health. They concluded that IS is associated with
      infectious and cardiovascular disease but not cancer or all-cause mortality and
      discussed a clear agenda for future research. However, the evidence on IS and
      health is mixed, and there still is much to be learned about the pathways that
      underpin these associations and moderators that reveal at what age and in what
      subgroups such associations hold. Marin and Miller noted that a toxic core of IS
      could be social inhibition, a related but distinct trait that refers to inhibited
      behavior during social interaction. On the basis of their proposition, I suggest
      an alternative model that points to social inhibition as an underlying trait that
      paves the way to IS. Social inhibition is a major determinant of chronic social
      stress in children and nonhuman primates. Yet, it remains uncertain whether
      social inhibition and its interaction with negative affectivity in Type D
      personality, is also related to health outcomes in adults. Many other challenges
      remain, but this important work of Marin and Miller highlights the need for more
      research on IS, social inhibition, and health.

PMID- 24016234
TI  - Taking the middle ground, where the path is most clear: reply to Smith (2013) and
      Denollet (2013).
AB  - We appreciate the thoughtful comments on Marin and Miller (2013). Both
      commentaries questioned the validity of our conclusions about interpersonal
      sensitivity (IS) and health, with Smith (2013) arguing that we overstated the
      conclusions and Denollet (2013) arguing that we did not take them far enough.
      Here we offer a middle-ground approach to interpreting the IS-health literature.
      We discuss our rationale for including introversion as an IS construct, and we
      point readers to high-quality evidence that specifically rules out some of the
      competing explanations raised by Smith (2013). Finally, we argue that additional
      work in this area is needed before specific hypotheses about biological
      mechanisms and the roles of age and disease stage as possible moderators can be
      tested.

PMID- 24016235
TI  - On the empirical status of the matching law: comment on McDowell (2013).
AB  - The matching law, regardless of the version, is a mathematical model that
      accounts for an organism's response rate as a function of the reinforcer rate.
      McDowell (2013) investigated to which extent a combined version of the
      quantitative law of effect (Herrnstein, 1970) and the generalized matching law
      (Baum, 1974) accounts for a substantial amount of the variance through several
      data sets. Even if I agree with most points raised by McDowell, there are 2
      important issues within his reanalysis. Two out of 6 studies relied on pooled
      subject data that are inappropriate for an investigation of the matching law
      (Caron, 2013). Moreover, the combined equation was not systemically investigated
      through all data sets. The current study casts some doubt on the empirical status
      of modern matching equations and thus shows that they still deserve extensive
      attention.

PMID- 24016236
TI  - Understanding matching theory and its application to data: reply to Caron (2013).
AB  - Caron (2013b) asserted in his comment on my article on the matching law and
      matching theory that a number of my analyses and conclusions were unsystematic,
      unreliable, doubtful, inappropriate, or violated theoretical assumptions. These
      assertions are based on mistakes and conceptual and theoretical
      misunderstandings. Specifically, my conclusions about Equation 6' are not
      affected by the parametric constraints applied when fitting it, and I used 2
      pooled data sets appropriately as part of my evaluation of Equations 7' and 8'.
      All the conclusions I reached in my article are valid, apply to individual
      subjects, and stand as I stated them.

PMID- 24016238
TI  - Cortical and cerebellar modulation of autonomic responses to loud sounds.
AB  - Detecting unexpected environmental change causes modulation of autonomic activity
      essential for survival. Understanding the neural mechanisms associated with
      responses to loud sounds may provide insights into the pathophysiology of
      posttraumatic stress disorder (PTSD), since individuals with PTSD exhibit
      heightened autonomic responses to unexpected loud sounds. We combined fMRI with
      autonomic psychophysiological assessment to investigate central and peripheral
      reactivity to loud tones in 20 healthy participants. Activity in anterior insula,
      pregenual anterior cingulate cortex, anterior midcingulate cortex, supplementary
      motor area, supramarginal gyrus, and cerebellar lobules VIII-IX was associated
      with both tones and concomitant skin conductance responses. Since regions
      signaling unexpected external events modulate autonomic activity, heightened loud
      tone autonomic responses in PTSD may reflect sensitization of this "salience"
      network. 

PMID- 24016237
TI  - Towards a better understanding of Rift Valley fever epidemiology in the south
      west of the Indian Ocean.
AB  - Rift Valley fever virus (Phlebovirus, Bunyaviridae) is an arbovirus causing
      intermittent epizootics and sporadic epidemics primarily in East Africa.
      Infection causes severe and often fatal illness in young sheep, goats and cattle.
      Domestic animals and humans can be contaminated by close contact with infectious
      tissues or through mosquito infectious bites. Rift Valley fever virus was
      historically restricted to sub-Saharan countries. The probability of Rift Valley
      fever emerging in virgin areas is likely to be increasing. Its geographical range
      has extended over the past years. As a recent example, autochthonous cases of
      Rift Valley fever were recorded in 2007-2008 in Mayotte in the Indian Ocean. It
      has been proposed that a single infected animal that enters a naive country is
      sufficient to initiate a major outbreak before Rift Valley fever virus would ever
      be detected. Unless vaccines are available and widely used to limit its
      expansion, Rift Valley fever will continue to be a critical issue for human and
      animal health in the region of the Indian Ocean. 

PMID- 24016239
TI  - A highly efficient luminescent Pt2Tl2 chain with a short Tl(I)-Tl(I) interaction.
AB  - The preparation of an unsupported tetranuclear cluster with a linear Pt(0)-Tl(I)
      Tl(I)-Pt(0) metal chain is described. The complex shows strong red emission in
      the solid state, having a quantum yield of 73%. Density functional theory (DFT)
      and time-dependent DFT calculations show that red emission originated from a
      platinum to thallium-thallium charge-transfer excited state. 

PMID- 24016243
TI  - Selective serotonin reuptake inhibitor (SSRI) toxicosis in cats: 33 cases (2004
      2010).
AB  - OBJECTIVE: To evaluate a population of cats with selective-serotonin reuptake
      inhibitor (SSRI) toxicosis and characterize the population affected, list
      products ingested, the clinical signs observed, treatments performed, length of
      hospitalization, patient outcome, and overall prognosis. DESIGN: Retrospective
      study from 2004 to 2010. SETTING: Referral veterinary center. ANIMALS: Thirty
      three witnessed cat SSRI ingestions. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The medical records of cats with a witnessed SSRI ingestion identified
      by review of an animal poison control center electronic database were evaluated.
      The most common SSRIs ingested were venlafaxine (Effexor; 12/33; 36%), fluoxetine
      (Prozac; 12/33; 36%), citalopram (Celexa; 6/33; 18%), and escitalopram (Lexapro;
      3/33; 9%). Overall, 24% of cats (8/33) became symptomatic, while 76% (25/33)
      remained asymptomatic. Of the symptomatic cats, sedation was the most common
      clinical sign (6/8; 75%), followed by gastrointestinal signs (4/8; 50%), central
      nervous system stimulation (1/8; 13%), cardiovascular signs (1/8; 13%), and
      hyperthermia (1/8; 13%). Veterinary care was sought in 20 cats (20/33; 61%).
      Sixteen cats (16/20; 80%) were hospitalized, while 4 cats (4/20; 20%) were
      treated as outpatients. Treatment for hospitalized patients included
      administration of IV fluid therapy (14/16; 88%), activated charcoal (12/16; 75%),
      anti-arrhythmic agents (7/16; 44%), methocarbamol (6/16; 38%), cyproheptadine
      (6/16; 38%), anti-emetics (5/16; 31%), and sedation (5/16; 31%). Diagnostics
      included blood work (7/16; 44%), blood pressure measurement (3/16; 19%), and
      electrocardiogram monitoring (2/16; 13%). Mean hospitalization time for all cases
      of SSRI ingestion was 14.6 +/- 7.8 hours (n = 16). All symptomatic cats in this
      study (8/8; 100%) had resolution of clinical signs and survived to discharge.
      CONCLUSIONS: The prognosis for SSRI ingestion in this population of cats was
      excellent. Decontamination and supportive care for at least 12-24 hours can be
      considered in cats with SSRI ingestion, particularly venlafaxine to monitor
      resolution of clinical signs.

PMID- 24016244
TI  - Gut hormones fulfill their destiny: from basic physiology to the clinic.

PMID- 24016245
TI  - The changes in age of peak swim speed for elite male and female Swiss freestyle
      swimmers between 1994 and 2012.
AB  - This study determined the age and its changes across years of peak swimming
      performance from 50 to 1,500 m freestyle. Data of 70,059 Swiss freestyle swimmers
      (33,725 women and 36,334 men) aged 10-40 years and competing from 50 to 1,500 m
      were analysed. The association between age and swimming speed of the annual ten
      fastest swimmers was investigated using single and multi-level hierarchical
      regression analyses. For women, age of peak swimming speed increased in 50 m from
      18.9 (s = 2.3) to 20.4 (s = 4.2) years but decreased in 1,500 m from 25.0 (s =
      13.1) (1996) to 18.1 (s = 3.7) years. For 100-800 m, age remained at 19.1 (s =
      1.1), 19.3 (s = 1.1), 18.7 (s = 1.5) and 18.5 (s = 1.3) years, respectively. For
      men, age of peak swimming speed decreased in 50 m from 23.0 (s = 4.0) to 23.0 (s
      = 3.5) but remained for 100-1,500 m at 22.5 (s = 1.4), 21.4 (s = 0.9), 20.3 (s =
      0.9), 20.3 (s = 0.9) and 20.3 (s = 1.1) years, respectively. Age was positively
      associated with swimming speed for 50-800 m, but negatively for 1,500 m. In
      conclusion, the age of peak swimming speed was younger in women compared to men
      for 50-800 m freestyle. For women, age of peak swimming speed increased in 50 m
      but decreased in 1,500 m freestyle across years. For men, age of peak swimming
      speed decreased in 50 m freestyle.

PMID- 24016246
TI  - Changes in insulin therapy regimens over 10 yr in children and adolescents with
      type 1 diabetes attending diabetes camps.
AB  - OBJECTIVE: To describe the changes in insulin therapy regimens of children and
      adolescents with type 1 diabetes over 10 yr and their correlation with hemoglobin
      A1c (HbA1c). RESEARCH DESIGN AND METHODS: The study included 7206 children and
      adolescents (age 12.8 +/- 2.7 yr, more than 1 yr of diabetes duration) admitted
      in summer camps between 1998 and 2007 (707-896/yr). Based on injection times
      (breakfast, lunch, afternoon, dinner, bedtime) and insulin types (short, long and
      premixed; human or analog), 786 different therapeutic combinations were
      classified in six main types of regimens. The distribution of the different
      regimens and their correlation with HbA1c were evaluated as a function of year
      and age. RESULTS: Over 10 yr, basal bolus increased from 13 to 52% and the pump
      from <1 to 13%, regimens with two to three injections per day decreased from 50
      to 25%, those with only premixed insulins from 33 to 7%, and diverse regimens
      from 9 to 1%. HbA1c was significantly higher with premixed insulin only, but
      there were no differences between the other regimens throughout the follow-up.
      Mean yearly HbA1c (8.21-8.45%) did not show any significant decrease, but the
      percentage of patients with HbA1c > 9 and 10% decreased significantly, in those
      treated with two to three injections and the pump, not with basal bolus or
      premixed only regimens. CONCLUSION: A major trend in intensifying insulin
      treatment in children and adolescents with type 1 diabetes was accompanied by
      modest improvements in HbA1c. No insulin regimen has shown any better results,
      except over premixed insulins.

PMID- 24016247
TI  - Vertical crystallization of C60 nanowires by solvent vapor annealing process.
AB  - We report that C60 molecules are spontaneously crystallized into vertical
      nanowires by the solvent vapor annealing (SVA) process. C60 molecules have been
      known to be assembled into wire-like crystals by simply dropping and drying C60
      solutions in m-xylene on a solid substrate. By the drop-drying process, C60
      nanowires have been mostly grown laterally on a solid substrate, as the major
      force applied to the droplet during the drying process is parallel to the
      substrate. On the other hand, the SVA process seems to provide an ideal
      environment under which the direction of the dominant drying force of a droplet
      becomes vertical. When a thermally evaporated C60 film is exposed to m-xylene
      solvent vapor under controlled SVA environments at room temperature, C60
      molecules are found to be crystallized into vertical nanowires. The effect of
      solvent vapor pressure on the vertical growth of C60 nanowire is examined by
      comparative studies using mesitylene and 1,3-dichlorobenzene. The versatility of
      the SVA process for the growth of vertical organic nanostructures is further
      demonstrated by the successful formations of vertically grown C60 2D disks and
      5,7,12,14-pentacenetetrone anisotropic crystals by employing carbon tetrachloride
      and toluene solvent vapors, respectively. 

PMID- 24016248
TI  - The influence of statin-fibrate combination therapy on lipids profile and
      apolipoprotein A5 in patients with acute coronary syndrome.
AB  - BACKGROUND: Statin-fibrate combination therapy has been used to treat patients
      with acute coronary syndrome (ACS) complicated by elevated triglycerides (TG) and
      decreased high density lipoprotein cholesterol (HDL-C). The purpose of this study
      was to evaluate the influence of the combination therapy on lipids profile and
      apolipoprotein A5 (apoA5) level in patients with ACS. METHODS: One hundred and
      four patients with ACS were recruited and randomly assigned into two groups: one
      was statin group (n = 52), given atorvastatin (20 mg QN) or other statins with
      equivalent dosages; the other was combination group (n = 52), given the same dose
      of statin plus bezafibrate (200 mg BID). Follow-up visits were scheduled at the
      end of 6 and 12 weeks post treatment. Serum apoA5 levels were determined using a
      commercial available ELISA kit. RESULTS: (1) Compared with that of statin
      monotherapy, statin-bezafibrate combination treatment not only resulted in a
      significant reduction of TG, TC and LDL-C levels, (all p < 0.05), but also led to
      increases in HDL-C and apoA5 levels (p < 0.05).(2) The percentage changes of TC,
      TG, LDL-C and apoA5 levels in both groups were even bigger at 12 weeks after
      treatment than that at 6 weeks (all p < 0.05). Similarly, the rates of achieving
      lipid-control target were higher in statin-bezafibrate combination treatment
      group than those in statin monotherapy group (all p < 0.05).(3) Spearman rank
      correlation analysis showed that the pre-treatment apoA5 level was positively
      correlated with TG (r = 0.359, p = 0.009). However, a negative correlation was
      observed between apoA5 and TG (r = -0.329, p = 0.017) after 12 weeks treatment.
      CONCLUSIONS: Statin and fibrate combination therapy is more effective than statin
      alone in achieving a comprehensive lipid control for ACS patients. Serum apoA5
      elevation after statin and fibrate combination treatment could be due to the
      synergistic effect of both drugs on hypertriglyceridemia control.

PMID- 24016249
TI  - Effect of juvenile hormone on senescence in males with terminal investment.
AB  - Senescence, a decline in survival and reproductive prospects with age, is
      controlled by hormones. In insects, juvenile hormone (JH) is involved in
      senescence with captive individuals, but its effect under natural conditions is
      unknown. We have addressed this gap by increasing JH levels in young and old wild
      males of the damselfly Hetaerina americana. We assessed survival in males that
      were treated with a JH analogue (methoprene), which is known to promote sexual
      activity, and an immune challenge, which is known to promote terminal investment
      in reproduction in the studied species. We replicated the same procedure in
      captivity (to control for environmental variation), where males were deprived of
      any activity or food. We expected old males to show the lowest survival after
      being treated with JH and immune-challenged, because the effect of terminal
      investment on senescence would be exacerbated by JH. However, this should be the
      case for wild animals, but not for captive animals, as the effects of JH and
      immune challenge should lead to an increase in high energetic-demanding
      activities only occurring in the wild. Old animals died sooner compared with
      young animals in both the wild and captivity, confirming that males are subject
      to senescence. In wild but not captive animals, JH decreased survival in young
      males and increased it in old males, confirming that JH is sensitive to the
      environment when shaping animal senescence. Immune challenge had no effect on
      survival, suggesting no effect of terminal investment on senescence.
      Additionally, contrary to the expected effects of terminal investment, with an
      immune challenge, recapture rates increased in young males and decreased in old
      males. Our results show that male senescence in the wild is mediated by JH and
      that terminal investment does not cause senescence. One explanation is that
      animals undergoing senescence and terminal investment modify their feeding
      behaviour to compensate for their physiological state. 

PMID- 24016251
TI  - Aqueous Mg2+ and Ca2+ ligand exchange mechanisms identified with 2DIR
      spectroscopy.
AB  - Biological systems must discriminate between calcium and magnesium for these ions
      to perform their distinct biological functions, but the mechanism for
      distinguishing aqueous ions has yet to be determined. Ionic recognition depends
      upon the rate and mechanism by which ligands enter and leave the first solvation
      shell surrounding these cations. We present a time-resolved vibrational
      spectroscopy study of these ligand exchange dynamics in aqueous solution. The
      sensitivity of the CN-stretch frequency of NCS(-) to ion pair formation has been
      utilized to investigate the mechanism and dynamics of ligand exchange into and
      out of the first solvation shell of aqueous magnesium and calcium ions with
      multidimensional vibrational (2DIR) spectroscopy. We have determined that anion
      exchange follows a dissociative mechanism for Mg(2+) and an associative mechanism
      for Ca(2+). 

PMID- 24016250
TI  - Molecular diagnosis of chronic granulomatous disease.
AB  - Patients with chronic granulomatous disease (CGD) suffer from recurrent, life
      threatening bacterial and fungal infections of the skin, the airways, the lymph
      nodes, liver, brain and bones. Frequently found pathogens are Staphylococcus
      aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia and
      Salmonella species. CGD is a rare (~1:250 000 births) disease caused by mutations
      in any one of the five components of the nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase in phagocytes. This enzyme generates superoxide and is
      essential for intracellular killing of pathogens by phagocytes. Molecular
      diagnosis of CGD involves measuring NADPH oxidase activity in phagocytes,
      measuring protein expression of NADPH oxidase components and mutation analysis of
      genes encoding these components. Residual oxidase activity is important to know
      for estimation of the clinical course and the chance of survival of the patient.
      Mutation analysis is mandatory for genetic counselling and prenatal diagnosis.
      This review summarizes the different assays available for the diagnosis of CGD,
      the precautions to be taken for correct measurements, the flow diagram to be
      followed, the assays for confirmation of the diagnosis and the determinations for
      carrier detection and prenatal diagnosis. 

PMID- 24016252
TI  - Association between TGF-beta1 polymorphisms and hepatocellular carcinoma risk: a
      meta-analysis.
AB  - BACKGROUND: Associations between transforming growth factor (TGF)-beta1
      polymorphisms and hepatocellular carcinoma (HCC) risk remained controversial.
      Therefore, we performed this meta-analysis to investigate these associations.
      METHODS: We searched Pubmed, EMBASE, Chinese National Knowledge Infrastructure
      (CNKI), and Wanfang databases for studies before March 2013. Odds ratios (ORs)
      with 95% confidence intervals (CIs) were used to calculate the strength of
      association. RESULTS: A total of 14 studies were included in this meta-analysis.
      TGF-beta1 +869C/T polymorphism was significantly associated with HCC risk
      (OR=1.74, 95% CI: 1.22-2.47, p=0.002). In addition, a significant association
      between -509C/T polymorphism and HCC risk was observed (OR=1.40, 95% CI: 1.15
      1.70, p=0.0007). Furthermore, significant associations between these
      polymorphisms and HCC risk were found in Asians and population-based studies.
      CONCLUSIONS: Our meta-analysis suggested that the TGF-beta1 +869C/T and -509C/T
      polymorphisms may be risk factors for developing HCC.

PMID- 24016253
TI  - Association between galactosylation of immunoglobulin G and improvement of
      rheumatoid arthritis during pregnancy is independent of sialylation.
AB  - Rheumatoid arthritis (RA) is known to improve during pregnancy and to flare after
      delivery. Changes in the glycosylation of immunoglobulin G (IgG)'s fragment
      crystallizable (Fc) have been suggested to play a role herein. Recent animal
      studies indicate that not galactosylation but mainly sialylation is important in
      this respect. We aim to find new associations between IgG-Fc N-glycosylation and
      improvement of RA during pregnancy and the flare after delivery. Sera of RA
      patients (n = 251 pregnancies) and healthy controls (n = 32), all participating
      in a prospective cohort study on RA and pregnancy (PARA study), were collected
      before conception, during pregnancy, and after delivery. Using a recently
      developed fast and robust nanoRP-HPLC-sheath-flow-ESI-MS method the glycosylation
      of IgG Fc-glycopeptides was measured in a subclass specific manner, with relative
      standard deviations of <4% for the 8 most abundant IgG Fc glycopeptides during
      the entire measurement period of over 3 weeks. In patients and controls, several
      glycosylation changes were observed during pregnancy. In depth analysis of the
      association of these glycosylation changes with disease activity revealed that
      galactosylation, independent of sialylation, is associated with improvement of RA
      during pregnancy. Functional studies in human cell systems should be performed to
      obtain more insight into this matter. 

PMID- 24016254
TI  - Forest production predicted from satellite image analysis for the Southeast Asia
      region.
AB  - BACKGROUND: The objective of this study was to demonstrate a new, cost-effective
      method to define the sustainable amounts of harvested wood products in Southeast
      Asian countries case studies, while avoiding degradation (net loss) of total wood
      carbon stocks. Satellite remote sensing from the MODIS sensor was used in the
      CASA (Carnegie Ames Stanford Approach) carbon cycle model to map forest
      production for the Southeast Asia region from 2000 to 2010. These CASA model
      results have been designed to be spatially detailed enough to support carbon
      cycle assessments in different wooded land cover classes, e.g., open woodlands,
      wetlands, and forest areas. RESULTS: The country with the highest average forest
      net primary production (NPP greater than 950 g C m-2 yr-1) over the period was
      the Philippines, followed by Malaysia and Indonesia. Myanmar and Vietnam had the
      lowest average forest NPP among the region's countries at less than 815 g C m-2
      yr-1. Case studies from throughout the Southeast Asia region for the maximum
      harvested wood products amount that could be sustainably extracted per year were
      generated using the CASA model NPP predictions. CONCLUSIONS: The method of using
      CASA model's estimated annual change in forest carbon on a yearly basis can
      conservatively define the upper limit for the amount of harvested wood products
      that can be removed and still avoid degradation (net loss) of the total wood
      carbon stock over that same time period.

PMID- 24016255
TI  - Tunable loading of single-stranded DNA on gold nanorods through the displacement
      of polyvinylpyrrolidone.
AB  - A quantitative and tunable loading of single-stranded (ss-DNA) molecules onto
      gold nanorods was achieved through a new method of surfactant exchange. This new
      method involves the exchange of cetyltrimethylammonium bromide surfactants for an
      intermediate stabilizing layer of polyvinylpyrrolidone and sodium dodecylsulfate.
      The intermediate layer of surfactants on the anisotropic gold particles was
      easily displaced by thiolated ss-DNA, forming a tunable density of single
      stranded DNA molecules on the surfaces of the gold nanorods. The success of this
      ligand exchange process was monitored in part through the combination of
      extinction, X-ray photoelectron, and infrared absorption spectroscopies. The
      number of ss-DNA molecules per nanorod for nanorods with a high density of ss-DNA
      molecules was quantified through a combination of fluorescence measurements and
      elemental analysis, and the functionality of the nanorods capped with dense
      monolayers of DNA was assessed using a hybridization assay. Core-satellite
      assemblies were successfully prepared from spherical particles containing a probe
      DNA molecule and a nanorod core capped with complementary ss-DNA molecules. The
      methods demonstrated herein for quantitatively fine tuning and maximizing, or
      otherwise optimizing, the loading of ss-DNA in monolayers on gold nanorods could
      be a useful methodology for decorating gold nanoparticles with multiple types of
      biofunctional molecules. 

PMID- 24016256
TI  - Focusing on outcomes and methods in removable prosthodontics trials: a systematic
      review.
AB  - OBJECTIVES: The aim of this study was to systematically examine the outcomes of
      interest of trials in removable prosthodontics and to assess their overall
      quality. MATERIAL AND METHODS: Electronic databases were searched up to August
      2011 and complemented by hand searching for published randomized controlled
      trials (RCTs) in the field of removable prosthodontics in the six major
      prosthodontic and implant journals. The primary outcome of RCTs was considered as
      the outcome of interest of this review, and only manuscripts in which the study's
      primary outcome was reported in the abstract were included. Outcomes were
      classified according to the Strength of Recommendation Taxonomy (SORT)
      classification. The quality of individual reports of RCTs was assessed following
      the Cochrane Handbook for Systematic Reviews of Interventions (Higgins & Green,
      www.cochrane-handbook.org). RESULTS: The search retrieved 86 reports of RCTs.
      Among these publications, 43% reported a patient-oriented primary outcome. Most
      of the publications did not present a clear description of sequence generation
      (54%) or allocation concealment (65%). Blinding of participants, clinicians, and
      outcomes assessors was not applicable or reported in most trials. Handling of
      withdrawals and losses was adequate in 52% of trials. CONCLUSIONS: Although
      published RCTs in removable prosthodontics have increased over time, efforts
      should be made to increase patient-reported outcomes and the methodological
      quality of these reports. Such improvement will lead to a better body of evidence
      in the field, thus providing increased support for clinical decision-making.

PMID- 24016257
TI  - Mobile primary healthcare services and health outcomes of children in rural
      Namibia.
AB  - INTRODUCTION: In rural areas of Namibia where health facilities are far apart,
      health outcomes are poor among high utilization groups such as pregnant women and
      children. Among children, orphans and vulnerable children (OVC) are generally
      more affected than non-OVC. This study assessed the health changes of orphans and
      other vulnerable and non-vulnerable children visiting a mobile clinic in rural
      Namibia. METHODS: Over a 6 month period, information on immunization status,
      diagnosis of anemia, skin and intestinal disorders, nutrition, dental disorders
      and referrals was collected from the records of a mobile clinic serving farms and
      surrounding areas in parts of rural Namibia. Data were compared for all children
      with visits in months 1 or 2 (baseline) and a visit in months 5 or 6 (follow up).
      Data for a cohort of children seen at both time points (the longitudinal group)
      were also analyzed. RESULTS: For all children, there was significant reduction in
      outstanding immunizations (5% to 1% p<0.0001), skin and intestinal parasites
      (15.5% to 0.2% p<0.0001), and stunting (26.9% to 14.2% p<0.0001) between baseline
      and follow up. Within the longitudinal group, reductions were observed in the
      prevalence of anemia (1.9% to 0.5% p<0.0001), incomplete immunizations (6.5% to
      <1% p<0.0001), and parasitic infections (16.9% to 0.2% p<0.0001) between the two
      time points. At baseline, orphans were more likely to have incomplete
      immunizations and parasitic infections. Among orphans, incomplete immunizations
      declined from 25% to 0 (p<0.001) while parasitic infections decreased from 22.7%
      to 0 (p<0.001). Among other vulnerable children incomplete immunizations declined
      from 5% to 1% (p=0.002), as did skin and parasitic infestations (17.2% to 0.3%
      p<0.001). CONCLUSION: Regular mobile clinic visits improved the health indices of
      child attendees. The greatest change was among OVC whose disease burden was
      greater at baseline. Mobile clinics may be an effective intervention in hard-to
      reach, resource-limited settings.

PMID- 24016258
TI  - Unusual inner C-alkylation of 2-N-substituted N-confused porphyrin cobalt
      complexes in toluene and p-xylene.
AB  - The inner C-benzyl- and C-p-xylyl-substituted cobalt(II) complexes of a 2-N
      substituted N-confused porphyrin were synthesized from the reaction of 2
      NCH2COOCH2C6H5NCTPPH (1) and CoCl2.6H2O in toluene (or p-xylene), and the
      structures were revealed by single-crystal X-ray analysis. 

PMID- 24016259
TI  - Multimodality imaging to improve the safety and efficacy of epicardial ablation
      of scar-related ventricular tachycardia.

PMID- 24016260
TI  - The multiple sclerosis relapse experience: patient-reported outcomes from the
      North American Research Committee on Multiple Sclerosis (NARCOMS) Registry.
AB  - BACKGROUND: Among patients with relapsing-remitting multiple sclerosis, relapses
      are associated with increased disability and decreased quality of life. Relapses
      are commonly treated with corticosteroids or left untreated. We aimed to better
      understand patient perceptions of the adequacy of corticosteroids in resolving
      relapse symptoms. METHODS: We examined self-reported data from 4482 participants
      in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry
      regarding evaluation, treatment, and recovery from relapses. Pearson's chi-square
      test was used to analyze categorical variables, while logistic regression was
      used to assess factors associated with patients' perceptions. RESULTS: Forty
      percent (1775/4482) of respondents were simply observed for disease worsening,
      whereas 25% (1133/4482) were treated with intravenous methylprednisolone (IVMP)
      and 20% (923/4482) with oral corticosteroids; additional treatments included
      adrenocorticotropic hormone, plasmapheresis, intravenous immunoglobulin, and
      others. Among patients who responded to questions about their most recent
      relapse, 32% (363/1123) of IVMP-treated and 34% (301/895) of oral corticosteroid
      treated patients indicated their symptoms were worse one month after treatment
      than pre-relapse, as did 39% (612/1574) of observation-only patients; 30%
      (335/1122) of IVMP-treated patients indicated their treatment made relapse
      symptoms worse (13% [145/1122]) or had no effect (17% [190/1122]), as did 38%
      (340/894) of oral corticosteroid-treated patients (worse, 13% [116/894]; no
      effect, 25% [224/894]) and 76% (1162/1514) of observation-only patients (worse,
      17% [264/1514]; no change, 59% [898/1514]). CONCLUSIONS: Overall, patients with
      relapsing multiple sclerosis who receive treatment report better outcomes than
      those who are simply observed. However, a sizeable percentage of patients feel
      that their symptoms following corticosteroid treatment are worse than pre-relapse
      symptoms and that treatment had no effect or worsened symptoms. Patient
      perceptions of relapse treatment deserve more attention, and more effective
      treatment options are needed.

PMID- 24016261
TI  - New data regarding distribution of cattle ticks in the south-western Indian Ocean
      islands.
AB  - Recent studies have produced new insight into the origin and distribution of some
      cattle ticks in the south-western Indian Ocean islands. Rhipicephalus
      appendiculatus, introduced from Tanzania in 2002, is now well established on
      Grande Comore but has not yet reached the other islands of the archipelago
      (Moheli, Anjouan and Mayotte). Only one of the two clades identified in Africa
      has settled so far. Amblyomma variegatum, which was not supposed to be able to
      persist in the Antananarivo region (1300 m) nor in other Malagasy regions of high
      altitude without regular introductions of ticks by infested cattle, is now
      endemic as a general rule up to 1600 m although other regions of lower altitude
      (1400 m) are still free of the tick. This species remains confined in a small
      area of the west coast on La Reunion Island. On the contrary, Hyalomma dromedarii
      could not settle on Madagascar where it was introduced in 2008 and Rhipicephalus
      evertsi evertsi is not yet present in Grande Comore despite regular introductions
      by infested cattle from Tanzania. A phylogeographic approach has been carried out
      at an intra-specific level for A. variegatum. This study has led to the
      identification of two main lineages, one covering all species distribution and
      one restricted to East Africa and the Indian Ocean area. These two lineages are
      in sympatry in Madagascar where a high genetic diversity has been described,
      whereas a lower genetic diversity is observed on other islands. These results
      seem to agree with the historical data concerning the introduction of the tick in
      the Indian Ocean area. 

PMID- 24016262
TI  - Plasticizer contamination in edible vegetable oil in a U.S. retail market.
AB  - With the wide application of plastics, the contamination of plasticizers
      migrating from plastic materials in the environment is becoming ubiquitous. The
      presence of phthalates, the major group of plasticizers, in edible items has
      gained increasingly more concern due to their endocrine disrupting property. In
      this study, 15 plasticizers in 21 edible vegetable oils purchased from a U.S.
      retail market were analyzed using gas chromatograph-mass spectrometry. Di(2
      ethylhexyl) phthalate (DEHP) and diisobutyl phthalate (DiBP) were detected in all
      oil samples. Benzylbutyl phthalate (BzBP), dibutyl phthalate (DBP), and diethyl
      phthalate (DEP) were detected at a rate of 95.2, 90.5, and 90.5%, respectively.
      The detection rates for all other plasticizers ranged from 0 to 57.1%. The
      content of total plasticizers in oil samples was determined to be 210-7558
      MUg/kg, which was comparable to the content range in oil marketed in Italy.
      Although no significant difference (p = 0.05) in the total content of plasticizer
      was observed among oil species (soybean, canola, corn, and olive), the wider
      range and higher average of total content of plasticizers in olive oil than other
      oil species indicated the inconsistence of plasticizer contamination in olive oil
      and a possible priority for quality monitoring. No significant difference (p =
      0.05) in the total content of plasticizers was found among glass-bottle (n = 4),
      plastic-bottle (n = 14), and metal-can (n = 3) packaging, implying that oil
      packaging is not the major cause of plasticizer contamination. The daily intake
      amount of plasticizers contained in edible oil on this U.S. retail market
      constituted only a minimum percentage of reference dose established by US EPA,
      thus no obvious toxicological effect might be caused. However, the fact that DEHP
      content in two olive oils exceeded relevant special migration limits (SMLs) of
      Europe and China might need attention. 

PMID- 24016263
TI  - Sleep duration and cardiovascular responses to stress in undergraduate men.
AB  - Short sleep has been related to incident cardiovascular disease, but
      physiological mechanisms accounting for this relationship are largely unknown.
      This study examines sleep duration and cardiovascular stress responses in 79
      healthy, young men. Sleep duration was assessed by wrist actigraphy for seven
      nights. Participants then completed a series of laboratory stress tasks while
      heart rate and blood pressure were monitored. Shorter total sleep time was
      related to a greater reduction in high-frequency heart rate variability during
      stress tasks, and to prolonged elevations in heart rate and diastolic pressure
      following tasks. Associations were independent of age, race, body mass index,
      caffeine intake, and smoking status. In sum, healthy young men with shorter
      actigraphy-assessed sleep exhibit less cardiac vagal activity, and poorer heart
      rate and diastolic blood pressure recovery, upon encountering stressful stimuli,
      than those with longer sleep. 

PMID- 24016265
TI  - The target of regulating the ATP-binding cassette A1 protein (ABCA1): promoting
      ABCA1-mediated cholesterol efflux in different cells.
AB  - The ATP-binding cassette A1 (ABCA1) transporter plays a major role in the efflux
      of lipids by mediating the cellular transport of phospholipids and cholesterol to
      lipid-poor/lipid-free apolipoprotein A-I (apoA-I) particles and thereby exerting
      important anti-atherogenic effects. Although the mechanism whereby ABCA1 mediates
      cholesterol efflux is not completely understood, numerous studies have shown
      that, in addition to apoA-I, the expression level of the total or cell surface
      ABCA1 protein is a determining factor for the activity of ABCA1-mediated
      cholesterol efflux, and defects in ABCA1-mediated cholesterol efflux lead to
      various pathological conditions in different cells, including cardiovascular and
      metabolic disorders. It has been widely demonstrated that a growing list of
      natural and synthetic substances and metabolic regulators that modulate the
      expression of ABCA1 not only act directly on the ABCA1 gene promoter, but also
      occurs at the post-transcriptional level via micro-RNAs and post-translationally
      through the stabilization or localization of the protein. The complex regulatory
      network of ABCA1 results in promoting or suppressing cholesterol efflux from
      cells, therefore we speculate that the ABCA1 transporter is emerging as a novel
      therapeutic target for cardiovascular and metabolic disorders. Thus, ABCA1 is a
      key modulator of cellular cholesterol efflux and contributes to functional
      disorders in different types of cells. 

PMID- 24016264
TI  - Regioselectivity of the oxidative C-S bond formation in ergothioneine and
      ovothiol biosyntheses.
AB  - Ergothioneine (5) and ovothiol (8) are two novel thiol-containing natural
      products. Their C-S bonds are formed by oxidative coupling reactions catalyzed by
      EgtB and OvoA enzymes, respectively. In this work, it was discovered that in
      addition to catalyzing the oxidative coupling between histidine and cysteine (1 
      > 6 conversion), OvoA can also catalyze a direct oxidative coupling between
      hercynine (2) and cysteine (2 -> 4 conversion), which can shorten the
      ergothioneine biosynthetic pathway by two steps. 

PMID- 24016266
TI  - Glioma targeting and anti-glioma effect of interleukin 13 peptide and RGD peptide
      dual functionalized nanoparticles.
AB  - Targeted nanoparticulated drug delivery systems have gained much attention owing
      to their potential in elevating anti-tumor effect and decreasing drug-originated
      side effects. In this contribution, a kind of dual glioma targeting delivery
      system was developed through co-modification nanoparticles with interlukin-13
      peptide (IL-13p) and RGD peptide (IRNPs), in which IL-13p could target to
      IL13Ralpha2 on tumor cells and RGD could target to alphavbeta3 on neovasculature.
      The model drug, docetaxel (DTX), could release from the unmodified nanoparticles
      (NPs) and IRNPs at a sustained manner. In vitro, the uptake of IRNPs by C6 (a
      glioma cell line) cells was time- and concentration-dependent, which was
      significantly higher than the uptake of NPs and single modified nanoparticles.
      After loading with DTX, IRNPs induced the highest percentage of apoptotic cells.
      In vivo, DTX-loaded IRNPs induced obviously higher apoptosis of cells in glioma
      site. These results indicated the dual modification could improve the cellular
      uptake as well as antitumor effect, which demonstrated IRNPs were promising drug
      delivery systems for glioma targeting treatment. 

PMID- 24016267
TI  - Molecular delivery of plasmids for genetic vaccination.
AB  - Plasmid vaccination is a smart gene delivery application mostly achieved through
      the utilisation of viral or copolymeric systems as surrogated carriers in micro
      or nano formulations. A common polymeric protocol for plasmid vaccine
      formulation, which as somewhat been successful, is via the complexation of the
      DNA molecules with a cationic polymer, and encapsulating in a vehicular carrier
      polymer. Even though plasmid vaccination research has not witnessed the much
      anticipated success, due a number of cellular and physicochemical reasons,
      application of copolymeric carriers with tight functionalities is a promising
      strategy to optimally deliver the DNA molecules; in view of the available
      chemistries and physical properties that could be tuned to enable enhanced
      targeted delivery, uptake and specific transfection. This also enables the
      targeting of specific epitopes and antigen presenting cells for the treatment of
      many pathogenic infections and cancer. This paper provides a brief critical
      review of the current state of plasmid vaccines formulation and molecular
      delivery with analysis of performance data obtained from clinical trials. 

PMID- 24016268
TI  - Edible transgenic plant vaccines for different diseases.
AB  - Edible plant vaccines are immunogenic preparations containing antigenic proteins
      rather than pathogens, therefore, they sanctify situation where there is a
      possibility of resurgence of disease when the antigenic preparation contains the
      organism in any form whatsoever. Expression of antigens as vaccines and of
      antibodies against antigens of pathogens in transgenic plants is a convenient and
      inexpensive source for various bacterial, viral, helminths, protozoan and
      autoimmune diseases with lower capital costs. This review describes various
      diseases along with the production of edible transgenic plant vaccines/proteins
      for the same. Thus, substituting and improvising conventional immunization
      methods. 

PMID- 24016269
TI  - Pharmacological activation of LXRs decreases amyloid-beta levels in Niemann-Pick
      type C model cells.
AB  - Niemann-Pick type C disease (NPC) is an inherited disorder mainly caused by loss
      of-function mutations in the NPC1 gene, that lead to intracellular cholesterol
      accumulation and disturbed cholesterol homeostasis. Similarly to Alzheimer's
      disease (AD), NPC is associated with progressive neurodegeneration and altered
      metabolism of amyloid precursor protein (APP). Liver X receptors (LXRs), the key
      transcriptional regulators of cholesterol homeostasis, were reported to play
      neuroprotective roles in NPC mice. We investigated the impacts of LXRs on APP
      metabolism in mutant CHO cells lacking the NPC1 gene (-NPC1 cells).
      Pharmacological activation of LXRs in -NPC1 cells tended to reduce the ratio of
      total secreted APP (sAPP) to full length APP (flAPP) levels and sAPPbeta levels
      as well as to increase the ratio of APP Cterminal fragments to flAPP levels,
      resulting in decreased levels of amyloid beta (Abeta) peptides. -NPC1 cells
      treated with LXR agonist TO901317 (TO90) displayed a modest increase in
      cholesterol efflux to apolipoprotein A-I (apoA-I) but not to HDL3, or in the
      absence of extracellular cholesterol acceptors. The observed similar reduction of
      Abeta levels upon TO90 treatment in the presence or in the absence of
      extracellular apoA-I indicated a cholesterol-efflux independent effect of TO90 on
      Abeta levels. Furthermore, TO90 had no effect on the cholesterol synthesis rate
      in -NPC1 cells, while it reduced the rate of cholesterol esterification. The
      obtained results indicate that LXR activation may decrease Abeta levels in NPC1-
      deficient conditions. The underlying mechanism of this action does not appear to
      be related to effects on cholesterol efflux or synthesis rates. 

PMID- 24016270
TI  - A neutralization scFv antibody against IL-1beta isolated from a NIPA-based
      bacterial display library.
AB  - OBJECTIVE: RA is one of autoimmune diseases, has drawn great attention of the
      world. Currently, the anti- IL-1beta monoclonal antibody Canakinumab (ACZ885) for
      treatment of RA has entered into clinical trials. However, Full length antibody
      has large molecular weight, and is difficult to penetrate the tissue or the
      nidus. In contrast, scFv has low molecular weight and strong penetration ability,
      and is favorable to increase the drug concentration in the indus, hence improving
      the efficacy of the drug. The aim of this study is to obtain a neutralizing scFv
      antibody from a combinatorial scFv library against hIL-1beta by the modified NLPA
      based bacterial display system, for further development of the small molecule
      antibody drug for treatment of RA. METHODS: The modified NIPA-based bacterial
      display system was used to construct the combinatorial scFv library derived from
      the spleen cDNA of immunized mice with hIL-1beta. FACS was used to screen hIL-
      1beta-binding clones with FITC-labeled hIL-1beta protein. Three clones were
      randomly selected from the third round of screening, and their nucleotide
      sequences were aligned with mouse immunoglobulin genes. The single chain antibody
      genes of the hIL-1beta-binding clones were subcloned into the prokaryotic
      expression vector pET-27b for expression. The molecular mass of the purified anti
      hIL-1beta single chain antibody was about 28ku. The hIL-1beta-binding ability of
      antibody were examined by ELISA and Western blot assays. Ability of the scFv
      antibody to neutralize hIL-1beta was evaluated by the MTT test. CONCLUSIONS: In
      this study, it is the first time to use the NIPA-based bacteria display system to
      construct and screen the combinatorial scFv library. Three scFvs against hIL
      1beta were obtained from the scFv library of the immunized mice. Prokaryotically
      expressed and purified scFvs demonstrate binding ability with hIL-1beta. Among
      the three clones. The MTT test suggests that scFv-20 is a neutralization antibody
      against hIL-1beta. The study provides a lead candidate for further development of
      small molecule therapeutic antibodies for treatment of RA.

PMID- 24016271
TI  - Air ions and respiratory function outcomes: a comprehensive review.
AB  - BACKGROUND: From a mechanistic or physical perspective there is no basis to
      suspect that electric charges on clusters of air molecules (air ions) would have
      beneficial or deleterious effects on respiratory function. Yet, there is a large
      lay and scientific literature spanning 80 years that asserts exposure to air ions
      affects the respiratory system and has other biological effects. AIMS: This
      review evaluates the scientific evidence in published human experimental studies
      regarding the effects of exposure to air ions on respiratory performance and
      symptoms. METHODS: We identified 23 studies (published 1933-1993) that met our
      inclusion criteria. Relevant data pertaining to study population characteristics,
      study design, experimental methods, statistical techniques, and study results
      were assessed. Where relevant, random effects meta-analysis models were utilized
      to quantify similar exposure and outcome groupings. RESULTS: The included studies
      examined the therapeutic benefits of exposure to negative air ions on respiratory
      outcomes, such as ventilatory function and asthmatic symptoms. Study specific
      sample sizes ranged between 7 and 23, and studies varied considerably by subject
      characteristics (e.g., infants with asthma, adults with emphysema), experimental
      method, outcomes measured (e.g., subjective symptoms, sensitivity, clinical
      pulmonary function), analytical design, and statistical reporting. CONCLUSIONS:
      Despite numerous experimental and analytical differences across studies, the
      literature does not clearly support a beneficial role in exposure to negative air
      ions and respiratory function or asthmatic symptom alleviation. Further,
      collectively, the human experimental studies do not indicate a significant
      detrimental effect of exposure to positive air ions on respiratory measures.
      Exposure to negative or positive air ions does not appear to play an appreciable
      role in respiratory function.

PMID- 24016272
TI  - Validating the multimedia activity recall for children and adolescents in a large
      New Zealand sample.
AB  - The aim of the study was to validate the self-report Multimedia Activity Recall
      for Children and Adolescents (MARCA) against accelerometry for the assessment of
      physical activity in New Zealand children. Participants (n = 716, 10-18 years)
      recalled 3-4 days of activity using the MARCA and underwent a partially
      overlapping 7-day accelerometry protocol during a national survey. Spearman
      correlation coefficients (rho) assessed the association between accelerometer
      derived counts per minute and MARCA-derived physical activity level and time in
      locomotion. Both data sources estimated time spent in light and moderate-vigorous
      physical activity. Association and agreement between methods for light physical
      activity and moderate-vigorous physical activity was assessed using correlations
      and Bland-Altman plots respectively, and paired t-tests conducted. Accelerometer
      derived activity counts were moderately correlated with both MARCA-derived
      physical activity level and locomotion (rho = 0.38, P < 0.0001). The correlation
      between methods was -0.14 for light physical activity and 0.28 for moderate
      vigorous physical activity (P < 0.0001). The MARCA overestimated moderate
      vigorous physical activity compared with accelerometry (120 min, P < 0.0001),
      which increased as moderate-vigorous physical activity time increased. Some sex
      and ethnicity (Maori [indigenous] versus non-Maori) differences were observed.
      Overall, the MARCA indicated moderate validity for assessment of physical
      activity level, locomotion and moderate-vigorous physical activity and poor
      validity for assessment of light physical activity. This was comparable to other
      self-report tools. The MARCA has utility for future large-scale research.

PMID- 24016273
TI  - Embracing the integrative.

PMID- 24016274
TI  - Is adolescence a sensitive period for sociocultural processing?
AB  - Adolescence is a period of formative biological and social transition. Social
      cognitive processes involved in navigating increasingly complex and intimate
      relationships continue to develop throughout adolescence. Here, we describe the
      functional and structural changes occurring in the brain during this period of
      life and how they relate to navigating the social environment. Areas of the
      social brain undergo both structural changes and functional reorganization during
      the second decade of life, possibly reflecting a sensitive period for adapting to
      one's social environment. The changes in social environment that occur during
      adolescence might interact with increasing executive functions and heightened
      social sensitivity to influence a number of adolescent behaviors. We discuss the
      importance of considering the social environment and social rewards in research
      on adolescent cognition and behavior. Finally, we speculate about the potential
      implications of this research for society. 

PMID- 24016275
TI  - Adoption: biological and social processes linked to adaptation.
AB  - Children join adoptive families through domestic adoption from the public child
      welfare system, infant adoption through private agencies, and international
      adoption. Each pathway presents distinctive developmental opportunities and
      challenges. Adopted children are at higher risk than the general population for
      problems with adaptation, especially externalizing, internalizing, and attention
      problems. This review moves beyond the field's emphasis on adoptee-nonadoptee
      differences to highlight biological and social processes that affect adaptation
      of adoptees across time. The experience of stress, whether prenatal,
      postnatal/preadoption, or during the adoption transition, can have significant
      impacts on the developing neuroendocrine system. These effects can contribute to
      problems with physical growth, brain development, and sleep, activating cascading
      effects on social, emotional, and cognitive development. Family processes
      involving contact between adoptive and birth family members, co-parenting in gay
      and lesbian adoptive families, and racial socialization in transracially adoptive
      families affect social development of adopted children into adulthood. 

PMID- 24016276
TI  - Beyond motivation: job and work design for development, health, ambidexterity,
      and more.
AB  - Much research shows it is possible to design motivating work, which has positive
      consequences for individuals and their organizations. This article reviews
      research that adopts this motivational perspective on work design, and it
      emphasizes that it is important to continue to refine motivational theories. In
      light of continued large numbers of poor-quality jobs, attention must also be
      given to influencing practice and policy to promote the effective implementation
      of enriched work designs. Nevertheless, current and future work-based challenges
      mean that designing work for motivation is necessary but insufficient. This
      review argues that work design can be a powerful vehicle for learning and
      development, for maintaining and enhancing employees' physical and mental health,
      and for achieving control and flexibility simultaneously (for example, in the
      form of ambidexterity); all these outcomes are important given the challenges in
      today's workplaces. The review concludes by suggesting methodological directions.

PMID- 24016280
TI  - Positive impact of an emergency department protocol on time to antimicrobial
      administration in dogs with septic peritonitis.
AB  - OBJECTIVE: To determine whether the development of a specific antimicrobial
      protocol for the treatment of canine intra-abdominal sepsis would improve time to
      appropriate antimicrobial administration following diagnosis of bacterial
      peritonitis. DESIGN: Case controlled observational study. SETTING: A tertiary
      referral small animal teaching hospital. ANIMALS: Twenty dogs undergoing surgery
      for septic peritonitis prior to the deployment of the abdominal sepsis protocol
      served as a case control population and 40 dogs identified as having septic
      peritonitis after deployment of the protocol served as the study population.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Median time from diagnosis of
      septic peritonitis to antimicrobial administration was 6 hours (range 1-10 h) in
      the preprotocol group (PRE), and 1 hour (range 1-2 h) in the postprotocol group
      (POST) (P = 0.001). Five of 20 (25%) culture and sensitivity results yielded
      negative cultures in the PRE versus 6 of 34 (17.6%) in the POST. Inappropriate
      empirical antimicrobials were selected 3 of 20 times (15%) in the PRE and 3 of 34
      times (8.8%) in the POST. The overall survival to discharge was 60% in the PRE
      and 70% in the POST (P = 0.425). CONCLUSIONS: The development of an emergency
      department antimicrobial protocol significantly decreased time to antimicrobial
      administration following identification of septic peritonitis in dogs.

PMID- 24016281
TI  - Novel analytical methods for flame retardants and plasticizers based on gas
      chromatography, comprehensive two-dimensional gas chromatography, and direct
      probe coupled to atmospheric pressure chemical ionization-high resolution time-of
      flight-mass spectrometry.
AB  - In this study, we assess the applicability of different analytical techniques,
      namely, direct probe (DP), gas chromatography (GC), and comprehensive two
      dimensional gas chromatography (GC * GC) coupled to atmospheric pressure chemical
      ionization (APCI) with a high resolution (HR)-time-of-flight (TOF)-mass
      spectrometry (MS) for the analysis of flame retardants and plasticizers in
      electronic waste and car interiors. APCI-HRTOFMS is a combination scarcely
      exploited yet with GC or with a direct probe for screening purposes and to the
      best of our knowledge, never with GC * GC to provide comprehensive information.
      Because of the increasing number of flame retardants and questions about their
      environmental fate, there is a need for the development of wider target and
      untargeted screening techniques to assess human exposure to these compounds. With
      the use of the APCI source, we took the advantage of using a soft ionization
      technique that provides mainly molecular ions, in addition to the accuracy of
      HRMS for identification. The direct probe provided a very easy and inexpensive
      method for the identification of flame retardants without any sample preparation.
      This technique seems extremely useful for the screening of solid materials such
      as electrical devices, electronics and other waste. GC-APCI-HRTOF-MS appeared to
      be more sensitive compared to liquid chromatography (LC)-APCI/atmospheric
      pressure photoionization (APPI)-HRTOF-MS for a wider range of flame retardants
      with absolute detection limits in the range of 0.5-25 pg. A variety of tri- to
      decabromodiphenyl ethers, phosphorus flame retardants and new flame retardants
      were found in the samples at levels from microgram per gram to milligram per gram
      levels. 

PMID- 24016282
TI  - Phototherapy rash in newborn infants: does it differ between conventional and
      light emitting diode phototherapy?
AB  - Data comparing the cutaneous side effects of light emitting diode (LED)
      phototherapy (LP) and conventional phototherapy (CP) devices in jaundiced newborn
      infants are very limited. We investigated the incidence and extent of skin
      eruptions caused by different phototherapy devices in preterm infants who are
      more prone to neonatal jaundice. This prospective, randomized controlled trial
      was conducted in the neonatal intensive care unit (NICU) of Hacettepe University
      Ihsan Dogramaci Childrens' Hospital in Ankara, Turkey. Preterm infants without
      skin lesions before and requiring phototherapy in the first week of life were
      included in the study. The infants were randomly assigned to receive CP or LP and
      were monitored closely for skin eruptions during phototherapy. Fifty-eight
      infants were included in the study: 25 (43.1%) received CP while 33 (56.9%)
      received LP. The duration of phototherapy was similar in the two groups (30.4 +/-
      9.6 hours and 31.8 +/- 15.6 hours, respectively). Baseline and control bilirubin
      levels were similar for the two groups (p = 0.101 and p = 0.105, respectively).
      The frequency of skin eruptions was 36% in the CP group and 33% in the LP group
      (p = 0.83). The skin eruptions were macules in 13 (22.4%), papules in 5 (8.6%),
      and maculopapular rashes in 2 (3.4%) infants.There were no differences in the
      incidence and extent of skin eruptions in preterm infants who received CP or LP.

PMID- 24016283
TI  - Late rebound of infantile hemangioma after cessation of oral propranolol.
AB  - Propranolol has become the first line of treatment for infantile hemangiomas
      (IHs), with a high response rate, but rebound growth after cessation of
      propranolol has been reported, primarily in the first year of life. We sought to
      determine the frequency and associated factors leading to late regrowth after
      successful treatment at an age when the proliferative phase has usually ceased.
      We retrospectively reviewed the clinical charts, serial photographs, and
      radiologic images of children with rebound IH occurring after the age of 15
      months after a successful course of oral propranolol averaging 2.6 mg/kg/day
      (range 2-3 mg/kg/day). Thirteen (10 female, 3 male) of 212 patients (6%) treated
      with oral propranolol since 2008 were evaluated. The mean age at the start of
      treatment was 5.3 months (range 1.8-13 months), and an average of 10.3 months
      (range 4.5-16 months) of treatment was given. It took an average of 5.3 months
      (range 1-13.8 months) for a significant rebound to appear. Late rebound after
      successful propranolol indicates a prolonged proliferation phase of IH even after
      15 months of age. This is compared with previous reports of rebound, which
      occurred primarily in infants younger than 1 year old. Late proliferation can
      occur in localized, small, mixed, and deep IH, even after several months of a
      positive response to propranolol. A second course of propranolol readily
      controlled the recurrence.

PMID- 24016284
TI  - Case report of drug rash with eosinophilia and systemic symptoms demonstrating
      human herpesvirus-6 reactivation.
AB  - Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug
      induced hypersensitivity syndrome that presents with diffuse cutaneous eruptions,
      fever, and multiorgan involvement. Here we present a pediatric case of DRESS
      complicated by human herpesvirus (HHV)-6 reactivation. After 1 week of
      sulfasalazine, our patient developed a diffuse morbilliform eruption.
      Sulfasalazine was discontinued. The patient presented to the emergency department
      soon thereafter with worsening eruption, fever, rigors, facial edema, and
      lymphadenopathy. Methylprednisolone was initiated. Peripheral smear did not
      demonstrate eosinophilia but showed toxic granulation with atypical lymphocytes.
      Transaminase levels and white blood cell count quickly became elevated, with
      increased eosinophils, suggesting DRESS. During the methylprednisolone taper, our
      patient experienced symptom exacerbation, acute hepatitis, and HHV-6
      seroconversion, indicating HHV-6 reactivation as the cause. As demonstrated by
      our patient, a decelerated methylprednisone taper is important because of
      potential symptom flaring during taper. Additionally, in the care of individuals
      with DRESS, HHV-6 is often tested for upon admission and not repeated. Delay in
      the rise of titers necessitates repeat testing.

PMID- 24016285
TI  - Recurrent sterile pustules and papules in a 7-month-old infant.

PMID- 24016287
TI  - Pattern ichthyosis in a newborn.

PMID- 24016286
TI  - A girl with eczematous lesions, multiple recurrent skin abscesses and
      mucocutaneous candidiasis.

PMID- 24016288
TI  - Mycoplasma pneumoniae-induced recurrent Stevens-Johnson syndrome in children: a
      case report.
AB  - Mycoplasma pneumoniae, the major pathogen of primary atypical pneumonia, is
      reported as the most common infectious agent associated with Stevens-Johnson
      syndrome (SJS) in children. For that reason it is important to consider
      mycoplasma infection also in the absence of classical pulmonary symptoms. SJS is
      a rare and acute, self-limited disease, characterized by severe inflammation and
      necrosis of two or more mucous membranes. We report the case of a 12-year-old boy
      with a diagnosis of SJS induced by M. pneumoniae infection. The patient's SJS
      relapsed 8 months after discharge. When the condition is recurrent, it is
      important early on to identify the cause of a single episode to optimize care and
      therapeutic choices.

PMID- 24016289
TI  - Multiple hair whorls in a child with normal cranial and neurologic development.
AB  - Hair whorls are a normal characteristic of the human scalp and abnormally placed
      or absent whorls have been associated with cranial or neurologic abnormalities.
      We report a case of multiple whorls in a child with normal neurologic
      development. We also include a brief review of the literature on the development
      of hair whorls and their associations. 

PMID- 24016290
TI  - Phototherapy and skin rashes.

PMID- 24016292
TI  - Species distribution models contribute to determine the effect of climate and
      interspecific interactions in moving hybrid zones.
AB  - Climate is a major factor delimiting species' distributions. However, biotic
      interactions may also be prominent in shaping geographical ranges, especially for
      parapatric species forming hybrid zones. Determining the relative effect of each
      factor and their interaction of the contact zone location has been difficult due
      to the lack of broad scale environmental data. Recent developments in species
      distribution modelling (SDM) now allow disentangling the relative contributions
      of climate and species' interactions in hybrid zones and their responses to
      future climate change. We investigated the moving hybrid zone between the
      breeding ranges of two parapatric passerines in Europe. We conducted SDMs
      representing the climatic conditions during the breeding season. Our results show
      a large mismatch between the realized and potential distributions of the two
      species, suggesting that interspecific interactions, not climate, account for the
      present location of the contact zone. The SDM scenarios show that the southerly
      distributed species, Hippolais polyglotta, might lose large parts of its southern
      distribution under climate change, but a similar gain of novel habitat along the
      hybrid zone seems unlikely, because interactions with the other species (H.
      icterina) constrain its range expansion. Thus, whenever biotic interactions limit
      range expansion, species may become 'trapped' if range loss due to climate change
      is faster than the movement of the contact zone. An increasing number of moving
      hybrid zones are being reported, but the proximate causes of movement often
      remain unclear. In a global context of climate change, we call for more interest
      in their interactions with climate change. 

PMID- 24016294
TI  - Influence of 2'-fluoro versus 2'-O-methyl substituent on the sugar puckering of
      4'-C-aminomethyluridine.
AB  - Herein, we report the synthesis of 4'-C-aminomethyl-2'-deoxy-2'-fluorouridine, a
      therapeutically appealing RNA modification. Conformational analysis by DFT
      calculations and molecular dynamics simulations using trinucleotide model systems
      revealed that modified sugar adopts C3'-endo conformation. In this conformer, a
      weak intramolecular C-H...F H-bond between the hydrogen atom of the 4'-C-CH2
      group and the F atom at the 2' position is observed. Comparative studies with
      unmodified, 2'-fluoro-, 2'-O-methyl-, and 4'-C-aminomethyl-2'-O-methyluridine
      showed the chemical nature of 2'-substituent dictates the sugar puckering of
      2',4'-modified nucleotides. 

PMID- 24016295
TI  - Revealing spectral features in two-photon absorption spectrum of Hoechst 33342: a
      combined experimental and quantum-chemical study.
AB  - We present the results of wide spectral range Z-scan measurements of the two
      photon absorption (2PA) spectrum of the Hoechst 33342 dye. The strongest 2PA of
      the dye in aqueous solution is found at 575 nm, and the associated two-photon
      absorption cross section is 245 GM. A weak but clearly visible 2PA band at ~850
      nm is also observed, a feature that could not be anticipated from the one-photon
      absorption spectrum. On the basis of the results of hybrid quantum
      mechanics/molecular mechanics calculations, we put forward a notion that the long
      wavelength feature observed in the two-photon absorption spectrum of Hoechst
      33342 is due to the formation of dye aggregates. 

PMID- 24016293
TI  - Multilevel context of depression in two American Indian tribes.
AB  - OBJECTIVE: Depression is a major debilitating disease. For American Indians
      living in tribal reservations, who endure disproportionately high levels of
      stress and poverty often associated with depression, determining the patterns and
      correlates is key to appropriate clinical assessment and intervention
      development. Yet little attention has been given to the cultural context of
      correlates for depression, including the influence of family, cultural traditions
      or practices, or community conditions. METHOD: We used data from a large
      representative psychiatric epidemiological study among American Indians in 2
      reservation communities to estimate nested individual and multilevel models of
      past-year major depressive episode (MDE) accounting for family, cultural, and
      community conditions. RESULTS: We found that models including culturally informed
      individual-level measures significantly improved the model fit over demographics
      alone. We found significant community-level variation in the probability of past
      year MDE diagnosis in 1 tribe even after accounting for individual-level
      characteristics. CONCLUSIONS: Accounting for culture, family, and community
      context will facilitate research, clinician assessment, and treatment of
      depression in diverse settings.

PMID- 24016296
TI  - A new approach to quantifying physical demand in rugby union.
AB  - The objective of the study was to describe an original approach to assessing
      individual workload during international rugby union competitions. The difference
      between positional groups and between the two halves was explored. Sixty-seven
      files from 30 French international rugby union players were assessed on a
      computerised player-tracking system (Amisco Pro((r)), Sport Universal Process,
      Nice, France) during five international games. Each player's action was split up
      into exercise and recovery periods according to his individual velocity
      threshold. Exercise-to-recovery (E:R) period ratios and acceleration were
      calculated. Results indicated that about 65% of exercise periods lasted less than
      4 s; half of the E:Rs were less than 1:4, and about one-third ranged between 1
      and 1:4 and about 40% of exercise periods were classified as medium intensity.
      Most acceleration values were less than 3 m.s(-2) and started from standing or
      walking activity. Back row players showed the highest mean acceleration values
      over the game (P < 0.05). No significant decrease in physical performance was
      seen between the first and second halves of the games except for back rows, who
      showed a significant decrease in mean acceleration (P < 0.05). The analysis of
      results emphasised the specific activity of back rows and tended to suggest that
      the players' combinations of action and recovery times were optimal for
      preventing large decrease in the physical performance.

PMID- 24016297
TI  - Cadmium uptake in Elodea canadensis leaves and its interference with extra- and
      intra-cellular pH.
AB  - This study investigated cadmium (Cd) uptake in Elodea canadensis shoots under
      different photosynthetic conditions, and its effects on internal (cytosolic) and
      external pH. The plants were grown under photosynthetic (light) or non
      photosynthetic (dark or in the presence of a photosynthetic inhibitor) conditions
      in the presence or absence of CdCl2 (0.5 MUm) in a medium with a starting pH of
      5.0. The pH-sensitive dye BCECF-AM was used to monitor cytosolic pH changes in
      the leaves. Cadmium uptake in protoplasts and leaves was detected with a Cd
      specific fluorescent dye, Leadmium Green AM, and with atomic absorption
      spectrophotometry. During cultivation for 3 days without Cd, shoots of E.
      canadensis increased the pH of the surrounding water, irrespective of the
      photosynthetic conditions. This medium alkalisation was higher in the presence of
      CdCl2 . Moreover, the presence of Cd also increased the cation exchange capacity
      of the shoots. The total Cd uptake by E. canadensis shoots was independent of
      photosynthetic conditions. Protoplasts from plants exposed to 0.5 MUm CdCl2 for 3
      days did not exhibit significant change in cytosolic [Cd(2+)] or pH. However,
      exposure to CdCl2 for 7 days resulted in increased cytosolic [Cd(2+) ] as well as
      pH. The results suggest that E. canadensis subjected to a low CdCl2 concentration
      initially sequesters Cd into the apoplasm, but under prolonged exposure, Cd is
      transported into the cytosol and subsequently alters cytosolic pH. In contrast,
      addition of 10-50 MUm CdCl2 directly to protoplasts resulted in immediate uptake
      of Cd into the cytosol.

PMID- 24016298
TI  - Elevated CD8 T cell responses in type 1 diabetes patients to a 13 amino acid
      coeliac-active peptide from alpha-gliadin.
AB  - Some type 1 diabetes (T1D) patients have been reported to exhibit T cell
      reactivity to wheat gluten. We tested the hypothesis that this T cell reactivity
      could be abolished by using prolyl-endopeptidase (PEP), an enzyme that cleaves
      peptide bonds after proline. Peripheral blood mononuclear cells (PBMCs) were
      isolated from T1D patients and healthy controls. PBMCs were stimulated with a
      peptic-tryptic digest of wheat gluten; a peptic-tryptic-PEP digest of wheat
      gluten; and a 13 amino acid peptide from wheat gluten. Fluorescent-labelled
      antibodies to CD3, CD4 and CD8 cell marker proteins were utilized to determine
      proliferative responses of CD3, CD4 and CD8 T cells. There were no significant
      differences in proliferative responses of CD3 or CD4 T cells to the wheat gluten
      antigens. A significantly higher proportion of CD8(+) T cells from T1D patients
      proliferated in the presence of the 13 amino acid peptide than when challenged
      with the peptic-tryptic or the peptic-tryptic-PEP digests of wheat gluten. PEP
      treatment had no significant effect on CD8 T cell reactivity to the peptic-trytic
      digest of wheat gluten. Our results suggest that wheat gluten-derived peptides,
      containing <= 13 amino acids, may evoke T cell responses in T1D patients. 

PMID- 24016299
TI  - Global metabolomic and network analysis of Escherichia coli responses to
      exogenous biofuels.
AB  - Although synthetic biology progress has made it possible to produce various
      biofuels in more user-friendly hosts, such as Escherichia coli, the large-scale
      biofuel production in these non-native systems is still challenging, mostly due
      to the very low tolerance of these non-native hosts to the biofuel toxicity. To
      address the issues, in this study we determined the metabolic responses of E.
      coli induced by three major biofuel products, ethanol, butanol, and isobutanol,
      using a gas chromatography-mass spectrometry (GC-MS) approach. A metabolomic data
      set of 65 metabolites identified in all samples was then subjected to principal
      component analysis (PCA) to compare their effects and a weighted correlation
      network analysis (WGCNA) to identify the metabolic modules specifically
      responsive to each of the biofuel stresses, respectively. The PCA analysis showed
      that cellular responses caused by the biofuel stress were in general similar to
      aging cells at stationary phase, inconsistent with early studies showing a high
      degree of dissimilarity between metabolite responses during growth cessation as
      induced through stationary phases or through various environmental stress
      applications. The WGCNA analysis allowed identification of 2, 4, and 2 metabolic
      modules specifically associated with ethanol, butanol, and isobutanol treatments,
      respectively. The biofuel-associated modules included amino acids and
      osmoprotectants, such as isoleucine, valine, glycine, glutamate, and trehalose,
      suggesting amino acid metabolism and osmoregulation are among the key protection
      mechanisms against biofuel stresses in E. coli. Interestingly, no module was
      found associated with all three biofuel products, suggesting differential effects
      of each biofuel on E. coli. The findings enhanced our understanding of E. coli
      responses to exogenous biofuels and also demonstrated the effectiveness of the
      metabolomic and network analysis in identifying key targets for biofuel
      tolerance. 

PMID- 24016300
TI  - The platform switching concept revisited. An experimental study in dogs.
AB  - OBJECTIVE: To evaluate the influence of the configuration of the marginal aspect
      of implants placed immediately into extraction sockets on peri-implant hard
      tissue adaptation. MATERIAL AND METHODS: In 6 Labrador dogs, endodontic
      treatments of the mesial roots of 1 M1 were performed and the distal roots were
      removed. 2 P2 was extracted as well. Implants were immediately placed in the
      center of the distal alveoli. Cylindrical straight implants were installed in the
      right side of the mandible (Control), while, in the left side, implants with a
      reduced diameter in the coronal portion, yielding an indentation in the surface
      continuity (Test), were installed. Cover screws were affixed, and the flaps were
      sutured to allow non-submerged healing. After 4 months of healing, histological
      slides were obtained for assessments. RESULTS: A buccal resorption of 1.58 +/-
      1.28 and 1.90 +/- 1.93 mm at the control and of 0.26 +/- 0.90 and 0.14 +/- 0.66
      mm at the test sites was observed at the premolar and molar regions,
      respectively. The buccal coronal level of osseointegration was located apically
      to the margin of the smooth/rough surface border by 2.40 +/- 0.90 and 3.70 +/-
      0.87 mm at the control sites and 1.19 +/- 0.45 and 2.16 +/- 0.96 mm at the test
      sites at the premolar and molar sites, respectively. All differences yielded
      statistical significance. CONCLUSIONS: The use of implants with a reduced
      diameter in their coronal aspect may contribute to preservation of the buccal
      bony crest in a more coronal level compared with conventional implants. Thus, the
      study confirmed the efficacy of the "platform switching" concept.

PMID- 24016301
TI  - Determinants of acute diarrhoea among children under five years of age in Derashe
      District, Southern Ethiopia.
AB  - INTRODUCTION: Diarrhoea kills more children than AIDS, malaria, and measles
      combined. Knowing the determinants of a disease enables us to design an effective
      intervention. The objective of this study was to identify the determinants of
      acute diarrhoea and associated factors among children under 5 years of age in
      Derashe district, south Ethiopia. METHODS: A community based unmatched case
      control study supplemented with Focus Group Discussions (FGDs) was employed in
      rural kebeles (neighborhoods) of the district. Collected data were entered in Epi
      Info v3.5.3 (wwwn.cdc.gov/epiinfo/info/) and descriptive data analyses were
      performed using SPSS v16.0 (www.spss.com). Binary logistic regression analysis
      was used to measure the association between dependent and independent variables,
      calculating<b> </b>odds ratios and 95% confidence intervals (CI). Statistical
      significance was set at alpha <=0.05. Multivariable analyses were applied to
      identify the relative effect of explanatory variables on the dependent variable.
      RESULTS: The study revealed that the occurrence of diarrhoea was significantly
      associated with lack of latrine ownership (adjusted [A] OR: 2.43, CI:1.19-4.87),
      lack of home-based water treatment (AOR: 2.25, CI:1.43-3.56), lack of improved
      water sources (AOR: 1.98, CI:1.16- 2.23) and consumption of left-over food (AOR:
      1.65, CI:1.01-2.71). CONCLUSIONS: The determinants of acute diarrhoea were of
      high preventive value (latrine ownership, availability of home-based water
      treatment, source of water and consumption of left-over food stored at room
      temperature), therefore health education on different mechanisms in diarrhoeal
      disease causation, and prevention methods, is recommended.

PMID- 24016302
TI  - Therapeutic effect and tolerability of gelatin sponge particle-mediated
      chemoembolization for colorectal liver metastases: a retrospective study.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide.
      The majority (approximately 60%) of patients with CRC will eventually develop
      liver metastases, which remain the most common cause of mortality in these
      patients. This study aimed to evaluate the therapeutic effect and tolerability of
      gelatin sponge particle (GSP)-mediated chemoembolization in the treatment of
      colorectal liver metastases after systemic chemotherapy failure. METHODS: This
      was a single-center retrospective study of 15 patients with colorectal liver
      metastases, who underwent GSP-mediated chemoembolization with 50 mg of lobaplatin
      during the period December 2009 to December 2010 in the Department of
      Interventional Radiology, Affiliated Zhongshan Hospital of Dalian University.
      Clinical data were retrieved, and the therapeutic effect and tolerability of the
      treatment were evaluated. RESULTS: All 15 patients with colorectal liver
      metastases completed the GSP-mediated chemoembolization. The therapeutic effect
      and tolerability were evaluated 3 months after the initial procedure. The tumor
      lesions in all patients showed various levels of necrosis and shrinkage.
      According to the Response Evaluation Criteria in Solid Tumors (RECIST), one
      patient achieved complete response (CR), eleven patients achieved partial
      response (PR), and three patients achieved stable disease (SD). The overall
      response rate (CR + PR) was 80%. CONCLUSIONS: GSP-mediated chemoembolization is
      well tolerated and has a good short-term response rate (80%) in the treatment of
      colorectal liver metastases after systemic chemotherapy failure. Collectively,
      further study of the long-term effect of GSP-mediated chemoembolization in
      colorectal liver metastasis in a large cohort is warranted.

PMID- 24016304
TI  - Activity profiles of professional soccer, rugby league and Australian football
      match play.
AB  - Abstract We compared the match activity profiles of elite footballers from
      Australian football (AF), rugby league (RL) and soccer (SOC), using identical
      movement definitions. Ninety-four elite footballers from AF, RL or SOC clubs in
      Australia participated in this study. Movement data were collected using a 5-Hz
      global positioning system from matches during the 2008-2011 competitive seasons,
      including measures of velocity, distance, acceleration and bouts of repeat
      sprints (RS). Australian footballers covered the greatest relative running
      distances (129 +/- 17 m.min-1) compared to RL (97 +/- 16 m.min-1) and SOC (104 +/
      10 m.min-1) (effect size [ES]; 1.0-2.8). The relative distance covered (4.92 +/-
      2.10 m.min-1 vs. 5.42 +/- 2.49 m.min-1; 0.74 +/- 0.78 m.min-1 vs. 0.97 +/- 0.80
      m.min-1) and the number of high-velocity running (0.4 +/- 0.2 no.min-1 vs. 0.4 +/
      0.2 no.min-1) and sprint (0.06 +/- 0.06 no.min-1 vs. 0.08 +/- 0.07 no.min-1)
      efforts between RL and SOC players were similar (ES; 0.1-0.3). Rugby league
      players undertook the highest relative number of accelerations (1.10 +/- 0.56
      no.min-1). RS bouts were uncommon for all codes. RL and SOC players perform less
      running than AF players, possibly due to limited open space as a consequence of
      field size and code specific rules. While training in football should be code
      specific, there may be some transference of conditioning drills across codes.

PMID- 24016303
TI  - Arginine improves peroxisome functioning in cells from patients with a mild
      peroxisome biogenesis disorder.
AB  - BACKGROUND: Zellweger spectrum disorders (ZSDs) are multisystem genetic disorders
      caused by a lack of functional peroxisomes, due to mutations in one of the PEX
      genes, encoding proteins involved in peroxisome biogenesis. The phenotypic
      spectrum of ZSDs ranges from an early lethal form to much milder presentations.
      In cultured skin fibroblasts from mildly affected patients, peroxisome biogenesis
      can be partially impaired which results in a mosaic catalase immunofluorescence
      pattern. This peroxisomal mosaicism has been described for specific missense
      mutations in various PEX genes. In cell lines displaying peroxisomal mosaicism,
      peroxisome biogenesis can be improved when these are cultured at 30 degrees C.
      This suggests that these missense mutations affect the folding and/or stability
      of the encoded protein. We have studied if the function of mutant PEX1, PEX6 and
      PEX12 can be improved by promoting protein folding using the chemical chaperone
      arginine. METHODS: Fibroblasts from three PEX1 patients, one PEX6 and one PEX12
      patient were cultured in the presence of different concentrations of arginine. To
      determine the effect on peroxisome biogenesis we studied the following
      parameters: number of peroxisome-positive cells, levels of PEX1 protein and
      processed thiolase, and the capacity to beta-oxidize very long chain fatty acids
      and pristanic acid. RESULTS: Peroxisome biogenesis and function in fibroblasts
      with mild missense mutations in PEX1, 6 and 12 can be improved by arginine.
      CONCLUSION: Arginine may be an interesting compound to promote peroxisome
      function in patients with a mild peroxisome biogenesis disorder.

PMID- 24016305
TI  - Versatile immunomagnetic nanocarrier platform for capturing cancer cells.
AB  - Sensitive and quantitative assessment of changes in circulating tumor cells
      (CTCs) can help in cancer prognosis and in the evaluation of therapeutics
      efficacy. However, extremely low occurrence of CTCs in the peripheral blood
      (approximately one CTC per billion blood cells) and potential changes in
      molecular biomarkers during the process of epithelial to mesenchymal transition
      create technical hurdles to the enrichment and enumeration of CTCs. Recently,
      efforts have been directed toward development of antibody-capture assays based on
      the expression of the common biomarker-the epithelial cell adhesion molecule
      (EpCAM) of epithelium-derived cancer cells. Despite some promising results, the
      assays relying on EpCAM capture have shown inconsistent sensitivity in clinical
      settings and often fail to detect CTCs in patients with metastatic cancer. We
      have addressed this problem by the development of an assay based on hybrid
      magnetic/plasmonic nanocarriers and a microfluidic channel. In this assay, cancer
      cells are specifically targeted by antibody-conjugated magnetic nanocarriers and
      are separated from normal blood cells by a magnetic force in a microfluidic
      chamber. Subsequently, immunofluorescence staining is used to differentiate CTCs
      from normal blood cells. We demonstrated in cell models of colon, breast, and
      skin cancers that this platform can be easily adapted to a variety of biomarkers,
      targeting both surface receptor molecules and intracellular biomarkers of
      epithelial-derived cancer cells. Experiments in whole blood showed capture
      efficiency greater than 90% when two cancer biomarkers are used for cell capture.
      Thus, the combination of immunotargeted magnetic nanocarriers with microfluidics
      provides an important platform that can improve the effectiveness of current CTC
      assays by overcoming the problem of heterogeneity of tumor cells in the
      circulation. 

PMID- 24016306
TI  - Circulating microparticles and plasma levels of soluble E- and P-selectins in
      patients with systemic sclerosis.
AB  - OBJECTIVES: Microparticles (MPs) may be involved in the pathogenesis of systemic
      sclerosis (SSc), which includes vasculopathy, endothelial cell activation, and
      coagulation activation. Circulating MPs from SSc patients were characterized and
      their relationship with soluble markers of vascular activation investigated.
      METHOD: This study included 121 SSc patients [79 with limited (lcSSc) and 42 with
      diffuse cutaneous SSc (dcSSc)] and 49 sex- and age-matched healthy controls
      (HCs). The MPs were characterized by flow cytometry for annexin V (AnxV)-binding
      capacity and their expression of surface markers of platelets (PMPs), leucocytes
      (LMPs), or endothelial cells (EMPs). Plasma levels of soluble (s) E- and P
      selectins were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      The total concentrations of MPs and of PMPs, LMPs, and EMPs were 22-42% lower in
      SSc patients than in HCs (p < 0.001). However, within the cell-derived MP pool, a
      47% higher fraction of AnxV non-binding MPs (F-AnxV(-) MPs) was found in the SSc
      patients compared to the HCs (p < 0.05). The plasma levels of sE- and sP
      selectins were increased by 47-64% in the SSc patients compared to HCs (p <
      0.001). Multiple regression analysis showed that the raised plasma levels of sE-
      and sP-selectin were associated with F-AnxV(-) EMPs in dcSSc patients (p = 0.008
      and p = 0.001, respectively) but not in lcSSc patients (p = 0.33 and p = 0.82,
      respectively). CONCLUSIONS: While the total number of MPs was decreased, the
      number of F-AnxV(-) MPs increased in SSc patients. The F-AnxV(-) EMPs were
      associated with plasma levels of markers of vascular activation in patients with
      dcSSc.

PMID- 24016308
TI  - Giant stretchability and reversibility of tightly wound helical carbon nanotubes.
AB  - There is a surging interest in 3D graphitic nanostructures which possess
      outstanding properties enabling them to be prime candidates for a new generation
      of nanodevices and energy-absorbing materials. Here we study the stretching
      instability and reversibility of tightly wound helical carbon nanotubes (HCNTs)
      by atomistic simulations. The intercoil van der Waals (vdW) interaction-induced
      flattening of HCNT walls prior to loading is constrained by the defects
      coordinated for the curvature formation of helices. The HCNTs exhibit extensive
      stretchability in the range from 400% to 1000% as a result of two distinct
      deformation mechanisms depending on the HCNT size. For small HCNTs tremendous
      deformation is achieved by domino-type partial fracture events, whereas for large
      HCNTs this is accomplished by stepwise buckling of coils. The formation and
      fracture of edge-closed graphene ribbons occur at lower temperatures, while at
      elevated temperatures the highly distributed fracture realizes a phenomenal
      stretchability. The results of cyclic stretching-reversing simulations of large
      HCNTs display pronounced hysteresis loops, which produce large energy dissipation
      via full recovery of buckling and vdW bondings. This study provides physical
      insights into the origins of high ductility and superior reversibility of hybrid
      CNT structures. 

PMID- 24016307
TI  - Driver self-regulation and depressive symptoms in cataract patients awaiting
      surgery: a cross-sectional study.
AB  - BACKGROUND: Cataract is an extremely common visual condition of ageing. Evidence
      suggests that visual impairment influences driving patterns and self-regulatory
      behavior among older drivers. However, little is known about the psychological
      effects of driver self-regulation among older drivers. Therefore, this study
      aimed to describe driver self-regulation practices among older bilateral cataract
      patients and to determine the association between self-regulation and depressive
      symptoms. METHODS: Ninety-nine older drivers with bilateral cataract were
      assessed the week before first eye cataract surgery. Driver self-regulation was
      measured via the Driving Habits Questionnaire. Depressive symptoms were assessed
      using the 20-item Center for Epidemiological Studies Depression Scale. Visual,
      demographic and cognitive data were also collected. Differences between self
      regulators and non self-regulators were described and linear regression modeling
      used to determine the association between driver self-regulation and depressive
      symptoms score. RESULTS: Among cataract patients, 48% reported self-regulating
      their driving to avoid at least one challenging situation. The situations most
      commonly avoided were driving at night (40%), on the freeway (12%), in the rain
      (9%) and parallel parking (8%). Self-regulators had significantly poorer contrast
      sensitivity in their worse eye than non self-regulators (p = 0.027). Driver self
      regulation was significantly associated with increased depressive symptoms after
      controlling for potential confounding factors (p = 0.002). CONCLUSIONS: Driver
      self-regulation was associated with increased depressive symptoms among cataract
      patients. Further research should investigate this association among the general
      older population. Self-regulation programs aimed at older drivers may need to
      incorporate mental health elements to counteract unintended psychological
      effects.

PMID- 24016309
TI  - Spontaneous atrioventricular nodal reentrant tachycardia in patients with
      idiopathic ventricular arrhythmias: the incidence, clinical, and
      electrophysiologic characteristics.
AB  - INTRODUCTION: Spontaneous or inducible atrioventricular nodal reentrant
      tachycardia (AVNRT) may coexist with idiopathic ventricular arrhythmias (IVAs).
      The aim of this study was to determine the incidence and the clinical and
      electrophysiologic characteristics of patients with spontaneous AVNRT among
      patients with IVAs. METHODS: Nine hundred eighty-seven consecutive patients with
      IVA (n = 398), patients with clinical and spontaneous AVNRT (n = 327), and
      patients with preexcitation syndrome (n = 262) were prospectively included in the
      study. RESULTS: Spontaneous AVNRT was present in 36 (9.0%) of 398 patients with
      IVA. The most common (97%) mode of presentation was palpitation due to
      spontaneous AVNRT. Absence of symptoms was frequent among patients with IVA and
      without spontaneous AVNRT compared to patients with IVA and spontaneous AVNRT
      (28.9% vs 0%, P = 0.0001). Patients with IVA and spontaneous AVNRT had lower
      median premature ventricular contraction (PVC) burden (1.9% vs 9.45%, P = 0.0001)
      and higher left ventricular ejection fraction (LVEF; 64.2 +/- 4.9% vs 59.2 +/-
      9.9%, P = 0.0001) compared to patients with IVA and without spontaneous AVNRT.
      Relatively high PVC burden (>=10%) was present in 19.4% of patients with
      spontaneous AVNRT and IVA. The prevalence of IVA was significantly higher in
      patients with AVNRT compared to patients with preexcitation syndrome (11% vs
      0.76%, P < 0.0001). CONCLUSIONS: Spontaneous AVNRT among patients with IVAs was
      relatively common in our study population. Spontaneous AVNRT in patients with
      IVAs can be a protective factor for left ventricular function. Greater LVEF in
      patients with spontaneous AVNRT and IVA compared to patients with IVA alone can
      be explained by earlier recognition of IVAs due to presence of symptomatic AVNRT
      and/or lower PVC burden.

PMID- 24016310
TI  - Lentiviral small hairpin RNA knockdown of macrophage inflammatory protein-1gamma
      ameliorates experimentally induced osteoarthritis in mice.
AB  - Immune cells are involved in the pathogenesis of osteoarthritis (OA). CD4(+) T
      cells were activated during the onset of OA and induced macrophage inflammatory
      protein (MIP)-1gamma expression and subsequent osteoclast formation. We evaluated
      the effects of local knockdown of MIP-1gamma in a mouse OA model induced by
      anterior cruciate ligament transection. The mouse macrophage cell lines and
      osteoclast-like cells generated from immature hematopoietic monocyte/macrophage
      progenitors of murine bone marrow were cocultured with either receptor activator
      of NFkappaB ligand (RANKL) or CD4(+) T cells. The levels of MIP-1gamma and RANKL
      in cells and mice were examined by enzyme-linked immunosorbent assay (ELISA). The
      osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase and
      cathepsin K staining. OA was induced in one hind-leg knee joint of B6 mice.
      Lentiviral vector encoding MIP-1gamma small hairpin RNA (shRNA) and control
      vector were individually injected intra-articularly into the knee joints, which
      were histologically assessed for manifestations of OA. The expression of MIP
      1gamma and matrix metalloproteinase (MMP)-13 and the infiltration of CD4(+) T
      cells, macrophages, and osteoclastogenesis in tissues were examined using
      immunohistochemistry. CD4(+) T cells were involved in OA by inducing MIP-1gamma
      expression in osteoclast progenitors and the subsequent osteoclast formation.
      Neutralizing MIP-1gamma with a specific antibody abolishes RANKL-stimulated and
      CD4(+) T-cell-stimulated osteoclast formation. MIP-1gamma levels were
      significantly higher in synovium and the chondro-osseous junction of joints 90
      days postsurgery. The number of infiltrated CD4(+) T cells and macrophages and IL
      1beta expression were reduced in the synovial tissues of mice treated with MIP
      1gamma shRNA. Histopathological examinations revealed that mice treated with MIP
      1gamma shRNA had less severe OA than control mice had, as well as decreased
      osteoclast formation and MMP-13 expression. Locally inhibiting MIP-1gamma
      expression may ameliorate disease progression and provide a new OA therapy.

PMID- 24016311
TI  - Leptospirosis in the western Indian Ocean islands: what is known so far?
AB  - In the past decade, leptospirosis has emerged as a major zoonosis with a
      worldwide distribution. The disease is caused by bacteria of the genus
      Leptospira. The western Indian Ocean includes more than one hundred tropical or
      subequatorial islands where leptospirosis constitutes a major public health
      problem. The clinical signs of the human disease are generally similar to an
      influenza-like syndrome, but acute forms of the disease are reported and
      mortality remains significant in this region. In animals, clinical forms are
      mainly asymptomatic but leptospirosis reduces the fertility of livestock,
      resulting in economic losses. The data available about human and animal
      leptospirosis in the western Indian Ocean islands are diverse: human
      leptospirosis has been extensively studied in Reunion Island, Mayotte, and the
      Seychelles, whereas the human clinical disease has never been described in
      Madagascar, Comoros, Mauritius, or Rodrigues, mainly because of the deficiency in
      appropriate medical and diagnostic structures. The rat is recognized as the major
      reservoir host for the bacteria on all islands, but recent data from Reunion
      Island indicates that almost all mammals can be a source of contamination. The
      incidence of leptospirosis in humans is highly seasonal, and linked to the rainy
      season, which is favorable for the environmental maintenance and transmission of
      the bacteria. The epidemiology of leptospirosis is fully island-dependent,
      related to the number of mammalian species, the origins of the introduced
      mammalian species, the relationships between humans and fauna, and environmental
      as well as cultural and socio-economic factors. 

PMID- 24016313
TI  - Electrophysiology of blunted emotional bias in psychopathic personality.
AB  - Diminished emotional capacity is a core characteristic of psychopathic
      personality. We examined behavioral and electrophysiological differences in
      attentional bias to emotional material in 34 healthy individuals rated high or
      low in psychopathic traits using the short form of the Psychopathic Personality
      Inventory-Revised (18 high-trait, 16 low-trait). While performing an emotional
      Stroop task, high-trait participants displayed reduced emotional modulation of
      the late positive potential (LPP, 400-600 ms), and early anterior positivity
      (EAP, 200-300 ms) amplitudes. Results suggest blunted bias to affective content
      in psychopathic personality, characterized by diminished early capture to
      emotional salience (EAP) and dampened cognitive emotional processing (LPP). 

PMID- 24016312
TI  - Comparison of heparinized saline and 0.9% sodium chloride for maintaining
      peripheral intravenous catheter patency in dogs.
AB  - OBJECTIVE: To determine whether heparinized saline would be more effective in
      maintaining the patency of peripheral IV catheters in dogs compared to 0.9%
      sodium chloride. DESIGN: Prospective blinded randomized study. SETTING:
      University Veterinary Teaching Hospital. ANIMALS: Thirty healthy purpose bred
      dogs, intended for use in the junior surgery laboratory, were utilized. The dogs
      were randomized into 1 of 3 groups, 2 treatment groups and a control group.
      INTERVENTIONS: An 18-Ga cephalic catheter was placed in the cephalic vein of each
      dog. Each dog in the treatment group had their catheter flushed with either 10
      IU/mL heparinized saline or 0.9% sodium chloride every 6 hours for 42 hours. The
      dogs in the control group did not have their catheters flushed until the end of
      the study period. Immediately prior to flushing catheters, each catheter was
      evaluated for patency by aspiration of blood and the catheter site was evaluated
      for phlebitis. MEASUREMENTS AND MAIN RESULTS: All dogs in the heparinized saline
      and 0.9% sodium chloride group had catheters that flushed easily at each
      evaluation point. More dogs in the saline group had catheters from which blood
      could not be aspirated, but there was no significant difference between these
      groups. All dogs in the control group had catheters that flushed easily at the
      end of the assigned 6 hour interval except in 1 dog. Phlebitis was not detected
      in any dog. CONCLUSIONS: Flushes of 0.9% sodium chloride were found to be as
      effective as 10 IU/mL heparinized saline flushes in maintaining patency of 18-Ga
      peripheral venous catheters in dogs for up to 42 hours. For peripheral catheters
      placed with the intention of performing serial blood draws, heparinized flushes
      may be warranted.

PMID- 24016314
TI  - Simultaneous fluorescence imaging of the activities of DNases and 3' exonucleases
      in living cells with chimeric oligonucleotide probes.
AB  - Real-time fluorescence imaging of the activity of nucleases in living cells has
      been a difficult issue because of unintended degradation of the natural
      oligonucleotides by nontarget nucleases or interactions with other proteins. In
      this work, we demonstrate two types of highly selective, sensitive, and robust
      oligonucleotide probes for simultaneous imaging of the activities of two
      different nucleases in living cells. The probes consist of the desired substrate
      structure of the target nuclease and partially phosphorothioate modified backbone
      labeled with fluorophore and quencher for protection from undesired degradation
      by other nucleases and signal transduction. Upon reaction with the target
      nuclease, the initially fluorescence quenched probe was cleaved and the
      fluorophore was separated from the quencher, giving out strong fluorescence
      signals. Two nucleases, DNase I and Exonuclease III, were employed as model
      enzymes to demonstrate the concept. In vitro studies proved that the two probes
      could discriminate their respective target nucleases in serum with high
      resistance to other coexisting enzymes. The lower limits of detection for DNase I
      and Exonuclease III were observed to be 40 U/L and 2.0 U/L, respectively. By
      labeling the two probes with different fluorophores and quenchers, simultaneous
      visualization of the activities of DNases and 3' exonucleases was achieved in
      both HeLa cells and the suspension cells of Arabidopsis thaliana. The developed
      approaches may greatly facilitate the studies on the intracellular functions of
      the two nucleases and other related biological processes. The probe design
      concept may also be further adapted to the detection of many other nucleases. 

PMID- 24016315
TI  - Diverse roles of ERECTA family genes in plant development.
AB  - Multiple receptor-like kinases (RLKs) enable intercellular communication that
      coordinates growth and development of plant tissues. ERECTA family receptors
      (ERfs) are an ancient family of leucine-rich repeat RLKs that in Arabidopsis
      consists of three genes: ERECTA, ERL1, and ERL2. ERfs sense secreted cysteine
      rich peptides from the EPF/EPFL family and transmit the signal through a MAP
      kinase cascade. This review discusses the functions of ERfs in stomata
      development, in regulation of longitudinal growth of aboveground organs, during
      reproductive development, and in the shoot apical meristem. In addition the role
      of ERECTA in plant responses to biotic and abiotic factors is examined. Elena D.
      Shpak (Corresponding author). 

PMID- 24016316
TI  - The effect of leg kick on sprint front crawl swimming.
AB  - The aim of this study was to examine the influence of leg kick on the pattern,
      the orientation and the propulsive forces produced by the hand, the efficiency of
      the arm stroke, the trunk inclination, the inter-arm coordination and the intra
      cyclic horizontal velocity variation of the hip in sprint front crawl swimming.
      Nine female swimmers swam two maximal trials of 25 m front crawl, with and
      without leg kick. Four camcorders were used to record the underwater movements.
      Using the legs, the mean swimming velocity increased significantly. On the
      contrary, the velocity and the orientation of the hand, the magnitude and the
      direction of the propulsive forces, as well as the Froude efficiency of the arm
      stroke were not modified. The hip intra-cyclic horizontal velocity variation was
      also not changed, while the index of coordination decreased significantly. A
      significant decrease (13%) was also observed in the inclination of the trunk.
      Thus, the positive effect of leg kick on the swimming speed, besides the obvious
      direct generation of propulsive forces from the legs, could probably be
      attributed to the reduction of the body's inclination, while the generation of
      the propulsive forces and the efficiency of the arm stroke seem not to be
      significantly affected.

PMID- 24016319
TI  - Revealing hidden helix propensity in Abeta peptides by molecular dynamics
      simulations.
AB  - Using all-atom explicit solvent model and exhaustive replica exchange molecular
      dynamics simulations we studied the conformational ensembles of several amino
      truncated Abeta peptides. In our simulations we specifically monitored the
      formation of helix structure in the C-terminals of various Abeta fragments. We
      show that the equilibrium distributions of structures adopted by Abeta23-40 and
      Abeta10-40 are similar, but sharply distinct from the conformational ensemble of
      Abeta29-40. The latter features a stable helical structure not present in longer
      fragments. Because the lambda-expansion method applied to Abeta23-40 identified
      Lys28 as the residue producing the strongest impact on the C-terminal helix
      structure, we hypothesized that addition of a single Lys28 to Abeta29-40 would
      change the peptide's conformational ensemble. REMD simulations of Abeta28-40
      confirmed this expectation by showing that in this peptide the helix conformation
      is destabilized and it adopts structures similar to those of Abeta23-40 and
      Abeta10-40. Therefore, a major conformational switch in the Abeta C-terminal
      occurs by truncating Abeta peptide after the position Lys28. By comparing our
      findings with previous studies we argue that Abeta C-terminal harbors helical
      propensity, which can be revealed by various factors, including environment,
      ligand binding, or sequence truncation. 

PMID- 24016318
TI  - Mechanosensitive channels are activated by stress in the actin stress fibres, and
      could be involved in gravity sensing in plants.
AB  - Mechanosensitive (MS) channels are expressed in a variety of cells. The molecular
      and biophysical mechanism involved in the regulation of MS channel activities is
      a central interest in basic biology. MS channels are thought to play crucial
      roles in gravity sensing in plant cells. To date, two mechanisms have been
      proposed for MS channel activation. One is that tension development in the lipid
      bilayer directly activates MS channels. The second mechanism proposes that the
      cytoskeleton is involved in the channel activation, because MS channel activities
      are modulated by pharmacological treatments that affect the cytoskeleton. We
      tested whether tension in the cytoskeleton activates MS channels. Mammalian
      endothelial cells were microinjected with phalloidin-conjugated beads, which
      bound to stress fibres, and a traction force to the actin cytoskeleton was
      applied by dragging the beads with optical tweezers. MS channels were activated
      when the force was applied, demonstrating that a sub-pN force to the actin
      filaments activates a single MS channel. Plants may use a similar molecular
      mechanism in gravity sensing, since the cytoplasmic Ca(2+) concentration increase
      induced by changes in the gravity vector was attenuated by potential MS channel
      inhibitors, and by actin-disrupting drugs. These results support the idea that
      the tension increase in actin filaments by gravity-dependent sedimentation of
      amyloplasts activates MS Ca(2+) -permeable channels, which can be the molecular
      mechanism of a Ca(2+) concentration increase through gravistimulation. We review
      recent progress in the study of tension sensing by actin filaments and MS
      channels using advanced biophysical methods, and discuss their possible roles in
      gravisensing. 

PMID- 24016317
TI  - Psychiatric disorders in 22q11.2 deletion syndrome are prevalent but
      undertreated.
AB  - BACKGROUND: Chromosome 22q11.2 deletion syndrome (22q11DS) is a common genetic
      disorder with high rates of psychosis and other psychopathologies, but few
      studies discuss treatment. Our aim was to characterize the prevalence and
      treatment of major psychiatric illnesses in a well-characterized sample of
      individuals with 22q11DS. METHOD: This was a cross-sectional study of 112
      individuals aged 8 to 45 years with a confirmed diagnosis of 22q11DS. Each
      participant was administered a modified Schedule for Affective Disorders and
      Schizophrenia for School-Age Children (K-SADS) and the Structured Interview for
      Prodromal Syndromes (SIPS). Phenotypes assessed were threshold and subthreshold
      psychosis, depression, mania, generalized and separation anxiety,
      obsessions/compulsions, inattention/hyperactivity and substance use. Histories of
      mental health care and current psychotropic treatment were obtained. RESULTS:
      Psychopathology was common, with 79% of individuals meeting diagnostic criteria
      for a disorder at the time of assessment. Diagnoses of psychosis were made in 11%
      of cases, attenuated positive symptom syndrome (APS) in 21%, and 47% experienced
      significant subthreshold symptoms. Peak occurrence of psychosis risk was during
      adolescence (62% of those aged 12-17 years). Criteria for a mood disorder were
      met by 14%, for anxiety disorder 34% and for attention deficit hyperactivity
      disorder (ADHD) 31%. Mental health care had been received by 63% of individuals
      in their lifetime, but only 40% continued therapy and 39% used psychotropics.
      Antipsychotics were used by 42% of participants with psychosis and none of the
      participants with APS. Half of those at risk for psychosis were receiving no
      mental health care. CONCLUSIONS: Psychopathology is common in 22q11DS but is not
      adequately treated or clinically followed. Particular attention should be paid to
      subthreshold psychotic symptoms, especially in adolescents.

PMID- 24016320
TI  - Not all pacemakers are created equal: MRI conditional pacemaker and lead
      technology.
AB  - Due to expanding clinical indications and an aging society there has been an
      increase in the use of implantable pacemakers. At the same time, due to increased
      diagnostic yield over other imaging modalities and the absence of ionizing
      radiation, there has been a surge in demand for magnetic resonance imaging (MRI)
      assessment, of both cardiac and noncardiac conditions. Patients with an
      implantable device have a 50-75% chance of having a clinical indication for MRI
      during the lifetime of their device. The presence of an implantable cardiac
      device has been seen as a relative contraindication to MRI assessment, limiting
      the prognostic and diagnostic utility of MRI in many patients with these devices.
      The introduction of MRI conditional pacemakers will enable more patients to
      undergo routine MRI assessment without risk of morbidity or device malfunction.
      This review gives a general overview of the principles and current evidence for
      the use of MRI conditional implantable cardiac devices. Furthermore, we appraise
      the differences between those pacemakers currently released to market. 

PMID- 24016321
TI  - The use of stem cells for the treatment of spinal surgical conditions.
AB  - Spinal pathologies are a major burden on society and individuals. Recent years
      have seen a large number of studies dedicated to the use of stem cells in spinal
      surgery. This review focuses on recent advances and controversies regarding the
      applications of stem cells in spinal fusion surgery, spinal cord injury and
      intervertebral disc degeneration. There are significant concerns regarding the
      ethics and risks of stem cell use. Animal models do not always accurately depict
      the human condition. While a great deal has been achieved, successful translation
      into clinical practice is needed. However there is no doubt that stem cells have
      a major role to play in the future management of spinal conditions. 

PMID- 24016322
TI  - Applications of stem cell therapy for physeal injuries.
AB  - Physeal injuries may lead to the formation of a bone bridge resulting in limb
      length discrepancies and angular deformity in children. Current treatment of
      physeal injuries may be challenging. A number of strategies have been used to
      repair physeal defects with varying results. Biological regeneration using stem
      cells is therefore an attractive potential future option to repair physeal
      defects. Preclinical animal studies using stem cells have shown mixed results.
      Studies have investigated the use of various scaffolds including chitin, collagen
      and gelfoam. Significant progress has been made in discovering appropriate growth
      factors such as transforming growth factor (TGF-beta), insulin-like growth factor
      (IGF-1), bone morphogenetic proteins (BMPs) and fibroblast growth factor (FGF-2)
      that could induce physeal repair and be used in combination with stem cell
      therapy. Advances have been made in the use of gene therapy to maintain
      sustainable delivery of growth factors to injury sites. This review discusses the
      current stem cell therapy available to repair physeal injuries. 

PMID- 24016323
TI  - The potential of stem cell therapy for osteoarthritis and rheumatoid arthritis.
AB  - Joint diseases are a major cause of disability and are a significant financial
      burden on health care systems. Regenerative medicine offers exciting
      possibilities for treating osteoarthritis and rheumatoid arthritis. As well as
      possessing the ability to differentiate into other tissue lineages, some stem
      cells such as mesenchymal stem cells possess immmunomodulatory properties that
      make them useful in the search for alternative treatments for rheumatoid
      arthritis specifically. Various studies have been carried out using animal models
      to evaluate the role of stem cells in the treatment of arthritis, with some
      research being translated into clinical studies. However, the number of patients
      used in some studies has left questions on the ability of stem cell therapy to
      treat arthritic conditions unanswered. This article reviews the innovative
      studies that have been carried out to treat arthritis using stem cells and also
      highlights the key challenges associated with these techniques. 

PMID- 24016324
TI  - A review of preclinical and clinical studies using synthetic materials for
      meniscus replacement.
AB  - The emerging field of tissue engineering holds the promise to use bio-materials
      for meniscus injury repair, namely scaffold or meniscus implant. Many implants
      have been studied and several studies have been conducted to verify the safety
      and quality of scaffolds. Preliminary data support the idea that synthetic
      implants can provide an alternative to menyscectomy helping to preserve the
      cartilage and preventing arthritis in patient with menisci injuries. However, the
      prevalence of postoperative complications varies within studies. Further
      investigations are required to evaluate the role of these materials in the
      clinical practice. 

PMID- 24016325
TI  - Stem cell therapy for knee ligament, articular cartilage and meniscal injuries.
AB  - Knee injuries involving ligament, articular cartilage and meniscus are common.
      The capacity for regeneration and repair of these tissues is limited due to their
      poor vascularity. Autologous or allogeneic stem cell transplantation has the
      potential to stimulate healing of these tissues. A number of preclinical studies
      of stem cell therapy for repair of these injuries have produced promising
      results. Further clinical trials are needed to test the efficacy of this
      technique. This paper reviews the development strategies, advances and clinical
      applications of stem cell therapies that are applicable to knee ligament,
      articular cartilage and meniscal injuries. 

PMID- 24016326
TI  - Synthetic grafts for anterior cruciate ligament reconstruction.
AB  - Several artificial biomaterials are available as ligament grafts. No ideal
      prosthesis mimicking natural human tissue have been found to date. The emerging
      field of tissue engineering holds the promise to use artificial ligaments as a
      viable alternative to the patellar or hamstring tendon autografts. Preliminary
      studies support the idea that these biomaterials have the ability to provide an
      alternative for autogenous grafts. However, no definitive conclusions have been
      found. Additionally, the incidence of postoperative complications varies within
      different studies. Prospective investigations are required to better understand
      the potential of artificial biomaterials as ligament grafts. 

PMID- 24016327
TI  - Potential of adipose derived stem cells in orthopaedic surgery.
AB  - Tissue engineering and cell therapies are currently being leveraged to find
      improved treatment strategies in orthopaedics. Adipose stem cells have been
      considered for their potential to differentiate into different cell lineages. The
      potential of adipose stem cells to restore chondral, bone and tendon tissue has
      been demonstrated in vivo and in vitro studies. Recently their capacity to
      restore cells and extracellular matrix of the intervetebral disc has been also
      investigated. Treatment of several orthopedic diseases could benefit from the
      application of adipose stem cells. However, there is still lack of knowledge
      about their clinical use and further studies are needed to better clarify their
      potential. 

PMID- 24016328
TI  - Advances and controversies in stem cell therapies and tissue engineering
      strategies applicable to trauma and orthopaedic surgery.

PMID- 24016329
TI  - Soybean proteomics for unraveling abiotic stress response mechanism.
AB  - Plant response to abiotic stresses depends upon the fast activation of molecular
      cascades involving stress perception, signal transduction, changes in gene and
      protein expression and post-translational modification of stress-induced
      proteins. Legumes are extremely sensitive to flooding, drought, salinity and
      heavy metal stresses, and soybean is not an exception of that. Invention of
      immobilized pH gradient strips followed by advancement in mass spectrometry has
      made proteomics a fast, sensitive and reliable technique for separation,
      identification and characterization of stress-induced proteins. As the functional
      translated portion of the genome plays an essential role in plant stress
      response, proteomic studies provide us a finer picture of protein networks and
      metabolic pathways primarily involved in stress tolerance mechanism. Identifying
      master regulator proteins that play key roles in the abiotic stress response
      pathway is fundamental in providing opportunities for developing genetically
      engineered stress-tolerant crop plants. This review highlights recent
      contributions in the field of soybean biology to comprehend the complex mechanism
      of abiotic stress acclimation. Furthermore, strengths and weaknesses of different
      proteomic methodologies of extracting complete proteome and challenges and future
      prospects of soybean proteome study both at organ and whole plant levels are
      discussed in detail to get new insights into the plant abiotic stress response
      mechanism. 

PMID- 24016330
TI  - Research and practice in childhood disability: what comes next?

PMID- 24016331
TI  - Promoting function and participation to improve living a life with cerebral
      palsy.

PMID- 24016332
TI  - Identification of a novel variant of LMP-1 of EBV in patients with endemic
      Burkitt lymphoma in western Kenya.
AB  - BACKGROUND: Epstein Barr virus (EBV) is a gammaherpesvirus that is associated
      with nasopharyngeal carcinoma (NPC) and endemic Burkitt lymphoma (eBL). EBV
      carries several latent genes that contribute to oncogenesis including the latent
      membrane protein 1 (LMP-1), a known oncogene and constitutively active CD40
      homolog. Variation in the C terminal region of LMP-1 has been linked to NPC
      pathogenesis, but little is known regarding LMP-1 variation and eBL. RESULTS: In
      the present study, peripheral blood samples were obtained from 38 eBL patients
      and 22 healthy controls in western Kenya, where the disease is endemic. The LMP-1
      C-terminal region from these samples was sequenced and analyzed. The frequency of
      a 30 base pair deletion of LMP-1 previously linked to NPC was not associated with
      eBL compared to healthy controls. However a novel LMP-1 variant was identified,
      called K for Kenya and for the G318K mutation that characterizes it. The K
      variant LMP-1 was found in 40.5% of eBL sequences and 25.0% of healthy controls.
      All K variant sequences contained mutations in both of the previously described
      minimal T cell epitopes in the C terminal end of LMP-1. These mutations occurred
      in the anchor residue at the C-terminal binding groove of both epitopes, a pocket
      necessary for MHC loading. CONCLUSIONS: Overall, our results suggest that there
      is a novel K variant of LMP-1 in Kenya that may be associated with eBL. Further
      studies are necessary to determine the functional implications of the LMP-1
      variant on early events in eBL genesis.

PMID- 24016333
TI  - Synthesis of a tetrasubstituted tetrahydronaphthalene scaffold for alpha-helix
      mimicry via a MgBr2-catalyzed Friedel-Crafts epoxide cycloalkylation.
AB  - alpha-Helices are ubiquitous protein recognition elements that bind diverse
      biomolecular targets. The synthesis of a small molecule scaffold to present the
      side chains of an alpha-helix is described. The 1,3,5,7-tetrasubstituted 1,2,3,4
      tetrahydronaphthalene scaffold, providing mimicry of the i, i+3, and i+4
      positions of an alpha-helix, was synthesized using a novel MgBr2-catalyzed
      Friedel-Crafts epoxide cycloalkylation as the key step. Each position may be
      differentiated via O-alkylation after scaffold synthesis, generating a diversity
      oriented approach to readily synthesize proteomimetics for different targets. 

PMID- 24016334
TI  - Prevalence of the metabolic syndrome in children with psoriatic disease.
AB  - Adults with psoriasis have a greater risk of developing metabolic syndrome (MetS)
      and cardiovascular disease (CVD), but few studies have investigated the
      prevalence of MetS and other risk factors for CVD in children with psoriasis. In
      an assessor-blinded study, 20 children ages 9-17 years with a current or
      previously documented history of psoriasis involving 5% or more of their body
      surface area or psoriatic arthritis were compared with a cohort of age- and sex
      matched controls with benign nevi, warts, or acne. MetS, our primary endpoint,
      was defined by the presence of abnormal values in at least three of the following
      measures: triglycerides, high-density lipoprotein cholesterol (HDL-C), fasting
      blood glucose (FBG), waist circumference, and blood pressure. Secondary endpoints
      included high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC),
      and low-density lipoprotein cholesterol (LDL-C). Thirty percent (6/20) of
      children with psoriasis met the criteria for MetS, compared with 5% (1/20) of the
      control group (p < 0.05). Subjects with psoriasis had higher mean FBG (91.1
      mg/dL) than the control group (82.9 mg/dL) (p = 0.01). There were no
      statistically significant differences in the other four components of MetS, BMI,
      BMI percentile, hs-CRP, TC, or LDL-C. The results of this trial demonstrate that
      children with psoriasis have higher rates of MetS than age- and sex-matched
      controls. It may therefore be important to evaluate children with psoriasis for
      components of MetS to prevent future CVD morbidity and mortality. 

PMID- 24016335
TI  - Physical measurement and evaluation of skin color changes under normal condition
      and post-ultraviolet radiation: a comparison study of Chromameter CM 2500d and
      Maxmeter MX18.
AB  - OBJECTIVE: To compare the data correlation between two kinds of instruments,
      Chromameter CM2500d and Maxmeter MX18, in the measurement of skin color changes
      under normal condition and post-ultraviolet (UV) radiation. METHOD: The data
      points of Chromameter CM2500d are based on L a values, while Maxmeter MX18 are
      based on M and E values, in order to compare the data correlation between these
      two kinds of instruments in skin color measurement on both non-exposed and
      exposed sites. In addition, an evaluation of the correlation of post-UV
      irradiation between these two instruments was conducted. Four different kinds of
      parameters post-UV radiation were measured including minimal erythema dose (MED),
      immediate pigmentation dose (IPD), minimal persistent pigmentation dose (MPPD)
      and repeated UV radiation. The following UV radiation dosages were applied as Day
      1=1.0 MED, Day 2=0.5 MED and Day 3=0.5 MED for repeated UV radiation, of which
      the erythema and pigmentation changes were recorded. RESULT: Chromameter CM2500d
      and Maxmeter MX18 showed good data correlation when measuring both non-exposed
      and exposed sites on normal skin. L values were affected more easily by UV
      induced erythema than M values on skin color changes after 1 MED and repeated UV
      exposures. IPD, MPPD and the pigmentation data showed good correlations with the
      measurement of the intensive erythema formation induced by repeated UV exposures.
      a value was shown to be equally effective as E value with skin erythema
      measurements in response to various MEDs. However, increased erythema induced by
      repeated UV radiations was able to reduce the correlations between a and E
      values. On the other hand, a and E were shown to be equally effective in
      recording the erythema change courses after strong erythema responses post-UV
      radiations. CONCLUSION: This comparative study showed that the data correlations
      between the two kinds of instruments were different depending on measurement
      conditions. Both Chromameter CM2500d and Maxmeter MX18 instrumental measurement
      results should be carefully evaluated by experimental conditions.

PMID- 24016336
TI  - Appalachian women's perspectives on breast and cervical cancer screening.
AB  - INTRODUCTION: Although breast and cervical cancer screening rates have been
      increasing over the three past decades, many Appalachian women in the USA do not
      receive screening, leading to disproportionate mortality rates. The aims of this
      study were to: (1) better understand barriers to and facilitators of breast and
      cervical cancer screening among Appalachian women; and (2) identify strategies to
      increase cancer screening. METHODS: Eight focus groups and 19 key informant
      interviews were conducted with 79 participants. Tape-recorded session were
      transcribed and content analyzed. RESULTS: Findings consistent with screening
      determinants research include: inadequate personal and community resources,
      attitudinal and knowledge barriers, and competing demands. Less commonly
      described factors include family cancer history, personal health habits, and the
      multiple influences of healthcare providers. CONCLUSIONS: Interpreting findings
      in terms of consumer information processing theory, healthcare providers and
      supports play a key role in educating and influencing the screening uptake among
      Appalachian Kentucky women. These findings have the potential to inform
      innovative and culturally consonant intervention approaches capable of increasing
      screening and decreasing mortality rates.

PMID- 24016337
TI  - Antibody-mimetic peptoid nanosheets for molecular recognition.
AB  - The ability of antibodies to bind a wide variety of analytes with high
      specificity and high affinity make them ideal candidates as molecular recognition
      elements for chemical and biological sensors. However, their widespread use in
      sensing devices has been hampered by their poor stability and high production
      cost. Here we report the design and synthesis of a new class of antibody-mimetic
      materials based on functionalized peptoid nanosheets. A high density of
      conformationally constrained peptide and peptoid loops are displayed on the
      surface of free-floating nanosheets to generate an extended, multivalent two
      dimensional material that is chemically and biologically stable. The nanosheet
      serves as a robust, high-surface area scaffold upon which to display a wide
      variety of functional loop sequences. The functionalized nanosheets were
      characterized by atomic force microscopy, X-ray diffraction, and X-ray
      reflectivity measurements, and were shown to serve as substrates for enzymes
      (protease and casein kinase II), as well as templates for the growth of defined
      inorganic materials (gold metal). 

PMID- 24016338
TI  - Methodological challenges in monitoring new treatments for rare diseases: lessons
      from the cryopyrin-associated periodic syndrome registry.
AB  - BACKGROUND: The Cryopyrin-Associated Periodic Syndromes (CAPS) are a group of
      rare hereditary autoinflammatory diseases and encompass Familial Cold
      Autoinflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS), and Neonatal Onset
      Multisystem Inflammatory Disease (NOMID). Canakinumab is a monoclonal antibody
      directed against IL-1 beta and approved for CAPS patients but requires post
      approval monitoring due to low and short exposures during the licensing process.
      Creative approaches to observational methodology are needed, harnessing novel
      registry strategies to ensure Health Care Provider reporting and patient
      monitoring. METHODS: A web-based registry was set up to collect information on
      long-term safety and effectiveness of canakinumab for CAPS. RESULTS: Starting in
      November 2009, this registry enrolled 241 patients in 43 centers and 13 countries
      by December 31, 2012. One-third of the enrolled population was aged < 18; the
      overall population is evenly divided by gender. Enrolment is ongoing for
      children. CONCLUSIONS: Innovative therapies in orphan diseases require post
      approval structures to enable in depth understanding of safety and natural
      history of disease. The rarity and distribution of such diseases and
      unpredictability of treatment require innovative methods for enrolment and follow
      up. Broad international practice-based recruitment and web-based data collection
      are practical.

PMID- 24016339
TI  - Global epidemiology of invasive meningococcal disease.
AB  - Neisseria meningitidis is one of the leading causes of bacterial meningitis
      globally and can also cause sepsis, pneumonia, and other manifestations. In
      countries with high endemic rates, the disease burden places an immense strain on
      the public health system. The worldwide epidemiology of invasive meningococcal
      disease (IMD) varies markedly by region and over time. This review summarizes the
      burden of IMD in different countries and identifies the highest-incidence
      countries where routine preventive programs against Neisseria meningitidis would
      be most beneficial in providing protection. Available epidemiological data from
      the past 20 years in World Health Organization and European Centre for Disease
      Prevention and Control collections and published articles are included in this
      review, as well as direct communications with leading experts in the field.
      Countries were grouped into high-, moderate-, and low-incidence countries. The
      majority of countries in the high-incidence group are found in the African
      meningitis belt; many moderate-incidence countries are found in the European and
      African regions, and Australia, while low-incidence countries include many from
      Europe and the Americas. Priority countries for vaccine intervention are high-
      and moderate-incidence countries where vaccine-preventable serogroups
      predominate. Epidemiological data on burden of IMD are needed in countries where
      this is not known, particularly in South- East Asia and Eastern Mediterranean
      regions, so evidence-based decisions about the use of meningococcal vaccines can
      be made. 

PMID- 24016340
TI  - Automatic identification and validation of planar collagen organization in the
      aorta wall with application to abdominal aortic aneurysm.
AB  - Arterial physiology relies on a delicate three-dimensional (3D) organization of
      cells and extracellular matrix, which is remarkably altered by vascular diseases
      like abdominal aortic aneurysms (AAA). The ability to explore the micro-histology
      of the aorta wall is important in the study of vascular pathologies and in the
      development of vascular constitutive models, i.e., mathematical descriptions of
      biomechanical properties of the wall. The present study reports and validates a
      fast image processing sequence capable of quantifying collagen fiber organization
      from histological stains. Powering and re-normalizing the histogram of the
      classical fast Fourier transformation (FFT) is a key step in the proposed
      analysis sequence. This modification introduces a powering parameter w, which was
      calibrated to best fit the reference data obtained using classical FFT and
      polarized light microscopy (PLM) of stained histological slices of AAA wall
      samples. The values of w = 3 and 7 give the best correlation (Pearson's
      correlation coefficient larger than 0.7, R 2 about 0.7) with the classical FFT
      approach and PLM measurements. A fast and operator independent method to identify
      collagen organization in the arterial wall was developed and validated. This
      overcomes severe limitations of currently applied methods like PLM to identify
      collagen organization in the arterial wall. 

PMID- 24016341
TI  - Innate sensing of viruses by pattern recognition receptors in birds.
AB  - Similar to mammals, several viral-sensing pattern recognition receptors (PRR)
      have been identified in birds including Toll-like receptors (TLR) and retinoic
      acid-inducible gene I (RIG-I)-like receptors (RLR). Avian TLR are slightly
      different from their mammalian counterparts, including the pseudogene TLR8, the
      absence of TLR9, and the presence of TLR1La, TLR1Lb, TLR15, and TLR21. Avian TLR3
      and TLR7 are involved in RNA virus recognition, especially highly pathogenic
      avian influenza virus (HPAIV), while TLR15 and TLR21 are potential sensors that
      recognize both RNA viruses and bacteria. However, the agonist of TLR15 is still
      unknown. Interestingly, chickens, unlike ducks, geese and finches, lack RIG-I,
      however they do express melanoma differentiation-associated gene 5 (MDA5) which
      functionally compensates for the absence of RIG-I. Duck RIG-I is the cytosolic
      recognition element for HPAIV recognition, while chicken cells sense HPAIV
      through MDA5. However, the contributions of MDA5 and RIG-I to IFN-beta induction
      upon HPAIV infection is different, and this may contribute to the chicken's
      susceptibility to highly pathogenic influenza. It is noteworthy that the
      interactions between avian DNA viruses and PRR have not yet been reported.
      Furthermore, the role for avian Nod-like receptors (NLR) in viral immunity is
      largely unknown. In this review, recent advances in the field of viral
      recognition by different types of PRR in birds are summarized. In particular, the
      tissue and cellular distribution of avian PRR, the recognition and activation of
      PRR by viruses, and the subsequent expression of innate antiviral genes such as
      type I IFN and proinflammatory cytokines are discussed. 

PMID- 24016343
TI  - Triage 2.0: re-evaluation of early patient assessment.

PMID- 24016342
TI  - Lower reference limits of quantitative cord glucose-6-phosphate dehydrogenase
      estimated from healthy term neonates according to the Clinical and Laboratory
      Standards Institute guidelines: a cross sectional retrospective study.
AB  - BACKGROUND: Previous studies have reported the lower reference limit (LRL) of
      quantitative cord glucose-6-phosphate dehydrogenase (G6PD), but they have not
      used approved international statistical methodology. Using common standards is
      expecting to yield more true findings. Therefore, we aimed to estimate LRL of
      quantitative G6PD detection in healthy term neonates by using statistical
      analyses endorsed by the International Federation of Clinical Chemistry (IFCC)
      and the Clinical and Laboratory Standards Institute (CLSI) for reference interval
      estimation. METHODS: This cross sectional retrospective study was performed at
      King Abdulaziz Hospital, Saudi Arabia, between March 2010 and June 2012. The
      study monitored consecutive neonates born to mothers from one Arab Muslim tribe
      that was assumed to have a low prevalence of G6PD-deficiency. Neonates that
      satisfied the following criteria were included: full-term birth (37 weeks); no
      admission to the special care nursery; no phototherapy treatment; negative direct
      antiglobulin test; and fathers of female neonates were from the same mothers'
      tribe. The G6PD activity (Units/gram Hemoglobin) was measured
      spectrophotometrically by an automated kit. This study used statistical analyses
      endorsed by IFCC and CLSI for reference interval estimation. The 2.5th
      percentiles and the corresponding 95% confidence intervals (CI) were estimated as
      LRLs, both in presence and absence of outliers. RESULTS: 207 males and 188
      females term neonates who had cord blood quantitative G6PD testing met the
      inclusion criteria. Method of Horn detected 20 G6PD values as outliers (8 males
      and 12 females). Distributions of quantitative cord G6PD values exhibited a
      normal distribution in absence of the outliers only. The Harris-Boyd method and
      proportion criteria revealed that combined gender LRLs were reliable. The
      combined bootstrap LRL in presence of the outliers was 10.0 (95% CI: 7.5-10.7)
      and the combined parametric LRL in absence of the outliers was 11.0 (95% CI: 10.5
      11.3). CONCLUSION: These results contribute to the LRL of quantitative cord G6PD
      detection in full-term neonates. They are transferable to another laboratory when
      pre-analytical factors and testing methods are comparable and the IFCC-CLSI
      requirements of transference are satisfied. We are suggesting using estimated LRL
      in absence of the outliers as mislabeling G6PD-deficient neonates as normal is
      intolerable whereas mislabeling G6PD-normal neonates as deficient is tolerable.

PMID- 24016344
TI  - Colin Award established by American-European Congress of Ophthalmic Surgeons.

PMID- 24016345
TI  - Femtosecond laser cataract incision morphology and corneal higher-order
      aberration analysis.
AB  - PURPOSE: Analysis of the femtosecond laser refractive lens surgery corneal
      incision configuration and corneal higher-order aberration (HOA) effect from the
      first postoperative day. METHODS: High-resolution anterior segment optical
      coherence tomography was used to assess 20 eyes undergoing femtosecond laser
      refractive lens surgery with 2.2-mm minimal incision. The primary incision (tri
      planar) actual length, cord length, surface angle, surface irregularity, and
      regional pachymetry values and the secondary incision (uni-planar) length, angle,
      surface irregularity, and pachymetry values were analyzed. Hartmann-Shack
      aberrometer was used to assess corneal HOAs to correlate the effect. Assessment
      was done preoperatively and 1 month postoperatively. RESULTS: The actual length,
      cord length, and surface angle means for the primary incision in the first
      postoperative day and month were 1.50 +/- 0.1 and 1.47 +/- 0.2 mm (P = .5), 1.41
      +/- 0.1 and 1.42 +/- 0.2 mm (P = .8), and 27 degrees  +/- 4 degrees  and 23
      degrees  +/- 5 degrees  (P = .07), respectively. The length and surface angle for
      the secondary incision in the first postoperative day and month were 1.17 +/-
      0.01 and 1.04 +/- 0.1 mm (P = .05) and 52 degrees  +/- 3 degrees  and 42 degrees 
      +/- 5 degrees  (P = .007). The regional pachymetry values for the primary and
      secondary incisions were significantly increased in the first postoperative day
      and then significantly decreased after 1 month. All irregularities occurred in
      the posterior surface (endothelium): 2 cases of posterior gap (first day) and 1
      case of posterior retraction (first month). The HOAs had not significantly
      changed preoperatively and after 1 month. CONCLUSIONS: The femtosecond laser
      refractive lens surgery incision is stable and does not significantly change the
      HOA.

PMID- 24016346
TI  - Influence of corneal cross-linking for keratoconus on several objective
      parameters of dry eye.
AB  - PURPOSE: To evaluate the potential influence of corneal cross-linking (CXL) with
      ultraviolet-A light and riboflavin in keratoconic eyes on several objective
      parameters of dry eye syndrome. METHODS: This prospective single center study
      included 30 consecutive eyes of 16 patients that underwent CXL with riboflavin
      and ultraviolet-A treatment (epithelial removal, 30 minutes soaking with
      riboflavin, 30 minutes of illumination with 365 nm, 3 mW/cm(2), 5 cm distance).
      Several dry eye syndrome parameters were evaluated preoperatively and 3 and 6
      months after the procedure: intra-individual comparison of fluorescein and Rose
      bengal staining, height of tear film meniscus, and tear film break-up time.
      RESULTS: Pathologic staining (more than 10 point-shaped areas or diffuse
      staining) with fluorescein was evident before CXL in 1 eye, 3 months after CXL in
      1 eye, and 6 months after CXL in 1 eye. Rose bengal staining 3 and 6 months
      postoperatively was comparable to preoperative staining. Tear film height was
      reduced in 2 eyes before CXL and in 4 eyes 3 months postoperatively, and was
      normal in all eyes after 6 months. The number of eyes with reduced tear film
      break-up time was not significantly changed. CONCLUSIONS: CXL had no significant
      impact on several parameters of dry eye syndrome 3 and 6 months postoperatively.

PMID- 24016347
TI  - Normal values for the size of a halo produced by a glare source.
AB  - PURPOSE: To determine the size of a halo in the visual field induced by bright
      light in healthy eyes of all ages using the Vision Monitor (MonCv3; Metrovision,
      Perenchies, France) and to assess the repeatability of the method. METHODS:
      Measurements were made in the right eyes of 147 healthy subjects (mean age: 48.2
      +/- 16.2 years) who were classified into six age groups. Using the Vision
      Monitor, optotypes of low luminance were presented at a distance of 2.5 m. The
      visual angle subtended by the radius of the halo was calculated in minutes of arc
      (arc min). The repeatability of the method was determined in a subset of 37
      subjects older than 50 years by calculating the Bland-Altman coefficient of
      repeatability. RESULTS: The mean radius of the halo was 111.6 +/- 39.8 arc min.
      Halo radius started to increase significantly from the age of 50 to 59 years. The
      relationship between halo radius and age (r = 0.65; P < .0001) was described by
      fitting a power function to the data. Halo size was independent of gender. The
      coefficient of repeatability of the method was +/-44 arc min. CONCLUSIONS: Halo
      size increases with age following a power model. The normal halo size values
      provided could help clinicians distinguish between normal or abnormal glare
      problems. The intersession repeatability observed for halo size measurement
      indicates this method could be useful for assessing visual impairment caused by
      glare.

PMID- 24016348
TI  - Intraoperative, real-time aberrometry during refractive cataract surgery with a
      sequentially shifting wavefront device.
AB  - PURPOSE: To introduce a new sequential wavefront device with rapid sampling that
      can be used as an intraoperative, real-time aberrometer/refractometer for
      immediate diagnosis and management of refractive outcomes during cataract
      surgery. METHODS: A unique wavefront device uses a rotating prismatic mirror to
      rapidly shift the incident wavefront emanating from the eye through an aperture
      for analysis of a sequentially sampled wavefront segment. The sampled segment is
      then focused onto a quad detector that localizes its angular displacement of the
      sampled segment's wavefront gradient. Although the device's capability is higher
      for other applications, the wavefront is herein rapidly sampled at 200 Hz
      (frames/second), with a 2-mm aperture that moves along a 5-mm outer diameter
      annulus to capture a real-time analysis of refractive error for intraoperative
      application (ie, an intraoperative wavefront movie). The prototype wavefront
      device has been miniaturized into a narrow profile attachment that can be fixed
      to an operating microscope. In pilot analysis, several eyes undergoing cataract
      surgery were analyzed to determine both the qualitative and quantitative change
      in refraction with surgical intervention in an effort to document and improve
      outcomes intraoperatively. RESULTS: Clinical application of the device was easily
      implemented without changing or limiting the working distance, magnification, or
      illumination of the surgeon's ergonomics intraoperatively. The real-time
      wavefront outcome was visualized overlaying a live eye image, presenting the
      refractive error both qualitatively and quantitatively. Qualitative
      representation of spherical refractive error was seen as a circle, cylinder as a
      thin ellipse, and emmetropia as a dot. Localization of lower-order aberrations
      with a practical sample rate of 200 frames/ second enables a real-time
      visualization of qualitative refractive data coaxially aligned with the eye image
      and quantitatively as sphere, cylinder, and axis at the bottom of the screen.
      Practical evaluation of residual cylinder prior to and during limbal relaxing
      incision placement, rotational accuracy during toric intraocular lens alignment,
      and refractive effect of subtle surgical maneuvers were all achieved with this
      device. CONCLUSION: Real-time, intraoperative refraction and visualization is
      possible with a new sequential wavefront device attached to the operating
      microscope. The precision and accuracy of intraoperative documentation and
      refinement of outcomes is likely to be enhanced, making this an important future
      tool for optimizing cataract surgery outcomes.

PMID- 24016349
TI  - Analysis of waveform-derived ORA parameters in early forms of keratoconus and
      normal corneas.
AB  - PURPOSE: To evaluate the Ocular Response Analyzer (ORA; Reichert Ophthalmic
      Instruments, Depew, NY) performance in differentiating grades I and II
      keratoconus from normal corneas using 41 parameters individually and to assess
      the effect of analyzing all parameters together. METHODS: This study compared the
      mean value of 41 ORA parameters in grades I and II keratoconus with healthy age
      matched control eyes. Only eyes with a central corneal thickness between 500 and
      600 MUm were included. The area under the receiver operating characteristic curve
      was calculated for each of the 41 parameters independently and for all of the
      parameters together. RESULTS: This study included 136 eyes with normal corneas
      and 68 eyes with grades I and II keratoconus. When analyzed individually, four
      ORA parameters (p1area, p1area1, p2area, and p2area1) had an area under the curve
      greater than 0.900 for discriminating between both groups. The p2area was the
      parameter that achieved the largest area under the curve individually (0.931).
      The area under the curve increased to 0.978 when analyzing all parameters
      together. CONCLUSION: Alternative ORA parameters are better for differentiating
      grades I and II keratoconus from normal corneas than the four parameters
      originally available for ophthalmologists (corneal hysteresis, Goldmann
      correlated intraocular pressure, corneal-compensated intraocular pressure, and
      corneal resistance factor). Although the ORA did not achieve 100% accuracy, the
      discrimination between these two groups was optimized by combining all
      parameters.

PMID- 24016350
TI  - Femtosecond laser-assisted cataract surgery in pediatric Marfan syndrome.
AB  - PURPOSE: To report femtosecond laser-assisted cataract surgery in pediatric
      Marfan syndrome. METHODS: Case report. RESULTS: A 10-year-old boy with ectopia
      lentis due to Marfan syndrome underwent femtosecond laser-assisted cataract
      surgery (Catalys Precision Laser System; OptiMedica, Sunnyvale, CA) under general
      anesthesia. Anterior capsulotomy was performed on the decentered lens. Routine
      irrigation/aspiration devices were used for lens and cortex removal. Centration
      of the capsular bag was achieved using a Cionni scleral fixation ring. A foldable
      intraocular lens was implanted. A free-positioned and precise sized capsulotomy
      was cut by the femtosecond laser. No intraoperative or postoperative
      complications were observed within the 10 weeks of follow-up. CONCLUSIONS: The
      use of a femtosecond laser has potential to perform a circular, well-centered
      capsulotomy for subsequent capsular tension ring and intraocular lens
      implantation without decentration in patients with Marfan syndrome.

PMID- 24016352
TI  - GaAs nanowires: from manipulation of defect formation to controllable electronic
      transport properties.
AB  - Reliable control in the crystal quality of synthesized III-V nanowires (NWs) is
      particularly important to manipulate their corresponding electronic transport
      properties for technological applications. In this report, a "two-step" growth
      process is adopted to achieve single-crystalline GaAs NWs, where an initial high
      temperature nucleation process is employed to ensure the formation of high Ga
      supersaturated Au7Ga3 and Au2Ga alloy seeds, instead of the low Ga supersaturated
      Au7Ga2 seeds observed in the conventional "single-step" growth. These two-step
      NWs are long (>60 MUm) and thick (>80 nm) with the minimal defect concentrations
      and uniform growth orientations. Importantly, these NWs exhibit p-type
      conductivity as compared to the single-step grown n-type NWs for the same
      diameter range. This NW conductivity difference (p- versus n-channel) is shown to
      originate from the donor-like crystal defects, such as As precipitates, induced
      by the low Ga supersaturated multicrystalline Au7Ga2 alloy seeds. Then the well
      controlled crystal quality for desired electronic properties is further explored
      in the application of large-scale p-type GaAs NW parallel array FETs as well as
      the integration of both p- and n-type GaAs NWs into CMOS inverters. All these
      illustrate the successful control of NW crystal defects and corresponding
      electronic transport properties via the manipulation of Ga supersaturation in the
      catalytic alloy tips with different preparation methods. The understanding of
      this relationship between NW crystal quality and electronic transport properties
      is critical and preferential to the future development of nanoelectronic
      materials, circuit design, and fabrication. 

PMID- 24016351
TI  - Further insights into the catalytical properties of deglycosylated pyranose
      dehydrogenase from Agaricus meleagris recombinantly expressed in Pichia pastoris.
AB  - The present study focuses on fragmented deglycosylated pyranose dehydrogenase
      (fdgPDH) from Agaricus meleagris recombinantly expressed in Pichia pastoris .
      Fragmented deglycosylated PDH is formed from the deglycosylated enzyme (dgPDH)
      when it spontaneously loses a C-terminal fragment when stored in a buffer
      solution at 4  degrees C. The remaining larger fragment has a molecular weight of
      ~46 kDa and exhibits higher volumetric activity for glucose oxidation compared
      with the deglycosylated and glycosylated (gPDH) forms of PDH. Flow injection
      amperometry and cyclic voltammetry were used to assess and compare the catalytic
      activity of the three investigated forms of PDH, "wired" to graphite electrodes
      with two different osmium redox polymers: [Os(4,4'-dimethyl-2,2'
      bipyridine)2(poly(vinylimidazole))10Cl](+) [Os(dmbpy)PVI] and [Os(4,4'-dimethoxy
      2,2'-bipyridine)2(poly-(vinylimidazole))10Cl](+) [Os(dmobpy)PVI]. When "wired"
      with Os(dmbpy)PVI, the graphite electrodes modified with fdgPDH showed a
      pronounced increase in the current density with Jmax 13- and 6-fold higher than
      that observed for gPDH- and dgPDH-modified electrodes, making the fragmented
      enzyme extraordinarily attractive for further biotechnological applications. An
      easier access of the substrate to the active site and improved communication
      between the enzyme and mediator matrix are suggested as the two main reasons for
      the excellent performance of the fdgPDH when compared with that of gPDH and
      dgPDH. Three of the four glycosites in PDH: N(75), N(175), and N(252) were
      assigned using mass spectrometry in conjunction with endoglycosidase treatment
      and tryptic digestion. Determination of the asparagine residues carrying
      carbohydrate moieties in PDH can serve as a solid background for production of
      recombinant enzyme lacking glycosylation. 

PMID- 24016353
TI  - Electrocardiographic smoke signals of fragmented QRS complex.

PMID- 24016354
TI  - EUS-guided drainage of liver abscess by using a lumen-apposing metal stent (with
      video).

PMID- 24016355
TI  - Intramural gastric abscess from dropped gallstones presenting as a subepithelial
      lesion (with video).

PMID- 24016356
TI  - Double-balloon enteroscopy for the diagnosis of Meckel's diverticulum in
      pediatric patients with obscure GI bleeding.

PMID- 24016357
TI  - Dynamics of the formation of a charge transfer state in 1,2-bis(9
      anthryl)acetylene in polar solvents: symmetry reduction with the participation of
      an intramolecular torsional coordinate.
AB  - We have studied 1,2-bis(9-anthryl)acetylene as a model compound for the
      characterization of the process of solvent-mediated symmetry reduction in an
      excited state. Thanks to the acetylenic bridge that joins the two anthracenic
      moieties, this system maintains minimal steric hindrance between the end
      chromophores in comparison with the classic 9,9'-bianthryl model compound. The
      acetylenic bridge also allows for significant electronic coupling across the
      molecule, which permits a redistribution of electron density after light
      absorption. Femtosecond resolved fluorescence measurements were used to determine
      the spectral evolution in acetonitrile and cyclohexane solutions. We observed
      that, for 1,2-bis(9-anthryl)acetylene, the formation of a charge transfer state
      occurs in a clear bimodal fashion with well separated time scales. Specifically,
      the evolution of the emission spectrum involves a first solvent-response mediated
      subpicosecond stage where the fluorescence changes from that typical of nonpolar
      solvents (locally excited) to an intermediate, partial charge transfer state. The
      second stage of the evolution into a full charge transfer state occurs with a
      much longer time constant of 37.3 ps. Since in this system the steric hindrance
      is minimized, this molecule can undergo much larger amplitude motions for the
      torsion between the two anthracenic moieties associated with the charge
      redistribution in comparison with the typical model compound 9,9'-bianthryl.
      Clearly, the larger range of motions of 1,2-bis(9-anthryl)acetylene gives the
      opportunity to study the electron transfer process with a good separation of the
      time scales for the formation of a partial charge transfer state, determined by
      the speed of solvent response, and the intramolecular changes associated with the
      formation of the fully equilibrated charge transfer state. 

PMID- 24016358
TI  - Canine parvovirus type 2c identified from an outbreak of severe gastroenteritis
      in a litter in Sweden.
AB  - A litter of recently-vaccinated puppies in Sweden experienced signs of severe
      haemorrhagic gastroenteritis. Canine parvovirus (CPV) was suspected as the cause
      of this outbreak on the basis of the clinical signs and the presence of
      parvoviral antigen in the faeces from one of the affected pups - confirmed using
      a commercial in-clinic faecal antigen ELISA test kit. A concern was raised about
      whether the vaccine (which contained a live, attenuated strain of CPV) could have
      caused the disease and so further faecal samples from the affected pups were
      submitted for laboratory virus isolation and identification.On cell culture, two
      out of four faecal samples were found to be virus-positive. This was confirmed as
      being canine parvovirus by immuno-staining with CPV specific monoclonal antibody.
      The virus was then tested using a series of PCR probes designed to confirm the
      identity of CPV and to distinguish the unique vaccine strain from field virus.
      This confirmed that the virus was indeed CPV but that it was not vaccine strain.
      The virus was then typed by sequencing the 426 amino acid region of the capsid
      gene which revealed this to be a type 2c virus.Since its emergence in the late
      1970s, canine parvovirus 2 (CPV2) has spread worldwide and is recognised as an
      important canine pathogen in all countries. The original CPV2 rapidly evolved
      into two antigenic variants, CPV2a and CPV2b, which progressively replaced the
      original CPV2. More recently a new antigenic variant, CPV2c, has appeared. To
      date this variant has been identified in many countries worldwide but there have
      been no reports yet of its presence in any Scandinavian countries. This case
      report therefore represents the first published evidence of the involvement of
      CPV2c in a severe outbreak of typical haemorrhagic gastroenteritis in a
      susceptible litter of pups in Scandinavia.

PMID- 24016360
TI  - Effects of small-sided game and change-of-direction training on reactive agility
      and change-of-direction speed.
AB  - The purpose of this study was to determine the effects of training change-of
      direction speed and small-sided games on performance in the Planned-AFL agility
      test and reactive agility. Twenty-five elite-standard U-18 Australian Rules
      football players were randomly allocated either to a change-of-direction group or
      a small-sided games group. Players participated in one or two 15-min sessions per
      week with 11 sessions conducted over a 7-week period during the season. Tests
      conducted immediately before and after the training period included the Planned
      AFL agility test and a video-based reactive agility test specific to Australian
      Rules football. The reactive agility test variables were total time, decision
      time and movement response time. The small-sided games group improved total time
      (P = 0.008, effect size = 0.93), which was entirely attributable to a very large
      reduction in decision time (P < 0.001, effect size = 2.32). Small-sided games
      produced a trivial change in movement response time as well as in the Planned-AFL
      agility test (P > 0.05). The change-of-direction training produced small to
      trivial changes in all of the test variables (P > 0.05, effect size = 0-0.2). The
      results suggest that small-sided games improve agility performance by enhancing
      the speed of decision-making rather than movement speed. The change-of-direction
      training was not effective for developing either change-of-direction speed as
      measured by the Planned-AFL test or reactive agility.

PMID- 24016359
TI  - Quantitative phosphoproteomics using acetone-based peptide labeling: method
      evaluation and application to a cardiac ischemia/reperfusion model.
AB  - Mass spectrometry (MS) techniques to globally profile protein phosphorylation in
      cellular systems that are relevant to physiological or pathological changes have
      been of significant interest in biological research. An MS-based strategy
      utilizing an inexpensive acetone-based peptide-labeling technique known as
      reductive alkylation by acetone (RABA) for quantitative phosphoproteomics was
      explored to evaluate its capacity. Because the chemistry for RABA labeling for
      phosphorylation profiling had not been previously reported, it was first
      validated using a standard phosphoprotein and identical phosphoproteomes from
      cardiac tissue extracts. A workflow was then utilized to compare cardiac tissue
      phosphoproteomes from mouse hearts not expressing FGF2 versus hearts expressing
      low-molecular-weight fibroblast growth factor-2 (LMW FGF2) to relate low
      molecular-weight fibroblast growth factor-2 (LMW FGF2)-mediated cardioprotective
      phenomena induced by ischemia/reperfusion injury of hearts, with downstream
      phosphorylation changes in LMW FGF2 signaling cascades. Statistically significant
      phosphorylation changes were identified at 14 different sites on 10 distinct
      proteins, including some with mechanisms already established for LMW FGF2
      mediated cardioprotective signaling (e.g., connexin-43), some with new details
      linking LMW FGF2 to the cardioprotective mechanisms (e.g., cardiac myosin binding
      protein C or cMyBPC), and also several new downstream effectors not previously
      recognized for cardio-protective signaling by LMW FGF2. Additionally, one of the
      phosphopeptides, cMyBPC/pSer-282, identified was further verified with site
      specific quantification using an SRM (selected reaction monitoring)-based
      approach that also relies on isotope labeling of a synthetic phosphopeptide with
      deuterated acetone as an internal standard. Overall, this study confirms that the
      inexpensive acetone-based peptide labeling can be used in both exploratory and
      targeted quantification phosphoproteomic studies to identify and verify
      biologically relevant phosphorylation changes in whole tissues. 

PMID- 24016361
TI  - Central regulation of body-fluid homeostasis.
AB  - Body-fluid homeostasis is essential to life, and the concentration of Na(+)
      ([Na(+)]) and osmolality in plasma and the cerebrospinal fluid (CSF) are
      continuously monitored in the brain. To maintain a physiological level of
      Na/osmolality in body fluids, the control of Na and water intake and excretion
      are of prime importance. Two independent sensing systems for [Na(+)] and
      osmolality in circumventricular organs (CVOs) have long been postulated to be
      involved in the monitoring of body-fluid conditions. In the past decade, several
      molecules were reported as promising candidates for these sensors - Nax for the
      [Na(+)] sensor and transient receptor potential (TRP) channels for the
      osmosensor. This review presents a summary of developments in these areas over
      recent years. 

PMID- 24016363
TI  - Responding to the Boston Marathon bombing: the unheralded role of graduate
      medical education.

PMID- 24016362
TI  - Double staining with crystal violet and methylene blue is appropriate for colonic
      endocytoscopy: an in vivo prospective pilot study.
AB  - BACKGROUND AND AIM: Endocytoscopy (EC) at ultra-high magnification enables in
      vivo visualization of cellular atypia of gastrointestinal mucosae. Clear images
      are essential for precise diagnosis by EC. The aim of the present study was to
      evaluate the optimal staining method for EC in the colon. METHODS: Thirty
      prospectively enrolled patients were allocated 1:1:1 to three distinct staining
      methods: 0.05% crystal violet (CV) alone, 1% methylene blue (MB) alone, or CV+MB
      (CM double). Normal rectal mucosae were stained with each dye and videos of EC
      images were recorded. Visibility of nuclei and gland formation after staining
      were evaluated as 'recognizable' or 'not recognizable'. Time for each parameter
      to become 'recognizable' was measured, and the average times for the three
      staining regimens were compared. RESULTS: MB alone and CM double staining
      resulted in 'recognizable' (102 +/- 27 vs 89 +/- 22 s, P=0.263) nuclei within
      comparable periods of time, whereas CV alone was unable to identify nuclei. Gland
      formation became 'recognizable' sooner after CM double staining than after MB
      alone (61 +/- 16 vs 108 +/- 24 s, P<0.001). CONCLUSIONS: Double staining with CV
      and MB, which rapidly provided recognizable images of both nuclei and gland
      formation, is an appropriate staining regimen for colonic EC.

PMID- 24016364
TI  - A critical evaluation of the Intercollegiate Surgical Curriculum and comparison
      with its predecessor the "Calman" curriculum.
AB  - BACKGROUND: The increasing need for doctors to be accountable and an emphasis on
      competency have led to the evolution of medical curricula. The Intercollegiate
      Surgical Curriculum Project succeeded the Calman curriculum for surgical training
      in 2007 in the UK. It sought to provide an integrated curriculum based upon a
      website platform. The aim of this review is to examine the changes to the
      curriculum and effect on surgical training. METHODS: A comparison was made of the
      Calman Curriculum and the ISCP and how they met training needs. RESULTS: The new
      curriculum is multifaceted, providing a more prescriptive detail on what trainees
      should achieve and when, as well as allowing portfolio, learning agreements, and
      work-based assessments to be maintained on an easily accessed website. The
      increasing emphasis on work-based assessments has been one of the major
      components, with an aim of providing evidence of competence. However, there is
      dissatisfaction amongst trainees with this component which lacks convincing
      validity. CONCLUSION: This new curriculum significantly differs from its
      predecessor which was essentially just a syllabus. It needs to continuously
      evolve to meet the needs of trainees whose training environment is ever changing.

PMID- 24016365
TI  - Application of stereoscopic visualization on surgical skill acquisition in
      novices.
AB  - OBJECTIVE: The use of stereoscopic imaging can provide additional depth cues that
      may increase trainee performance on surgical tasks, but it has yet to be
      evaluated using a validated surgical skill system. This study examines the
      influence of monoscopic vs stereoscopic visualization in novice trainees
      performing the McGill Inanimate System for Training and Evaluation of
      Laparoscopic Skill (MISTELS) tasks, a validated laparoscopic skill-evaluation
      system, predicting a difference in performance based on visualization modality.
      DESIGN: A total of 31 first- and second-year medical students at the University
      of Western Ontario were selected, each performed the MISTELS battery of tasks
      (circle cutting, peg transfer, ligated loop Placement, intracorporeal knot tying,
      and extracorporeal knot tying) using either monoscopic or stereoscopic
      visualization displays. Performance was evaluated in accordance with the MISTELS
      protocol. Participant visual spatial ability and manual dexterity skills were
      also analyzed and compared with performance. p values less than 0.05 were
      considered significant. RESULTS: For ligated loop placement, extracorporeal knot
      tying, and intracorporeal knot tying, no significant difference was found between
      monoscopic and stereoscopic visualization on task performance (p > 0.05).
      Monoscopic visualization was shown to produce significantly better performance in
      the peg transfer task alone (p = 0.001). Qualitatively, 57.1% of participants
      believed their performance was aided by stereoscopic visualization and 68.8%
      believed that future learners would benefit from its implementation into surgical
      education. Most participants rated the peg transfer task to be the least
      difficult task (60%) and rated the intracorporeal knot-tying task to be the most
      difficult (65.9%). CONCLUSIONS: These results suggest that the intrinsic
      difficulty of the MISTELS tasks may exceed a novice user's skill. No benefit with
      additional 3-dimensional cues in naive surgical trainees was found. Additional
      visual cues in stereoscopic visualization may only serve to increase cognitive
      load and potentially decrease skill acquisition and learning.

PMID- 24016366
TI  - Assessment of robotic simulation by trainees in residency programs of the
      Southeastern Section of the American Urologic Association.
AB  - OBJECTIVES: To assess the Southeast Section of the American Urological
      Association (SESAUA) trainee exposure to and thoughts on robotic simulation.
      DESIGN: Questionnaire-based study of SESAUA residency trainees to determine their
      access to robotic simulation, live robotic experience to date, and opinion
      regarding the adequacy of current robotic training. SETTING: Three trainees from
      each SESAUA training program were invited to Orlando, Florida for a formal 2-day
      robotic training course. Day 1 was a 3-component didactic session. Day 2 involved
      faculty directing the trainees in set tasks on a live porcine model for 4 hours
      and another 4 hours on the Mimic dV-Trainer (Mimic Technologies, Inc, Seattle,
      WA) for directed exercises. PARTICIPANTS: Thirty-two trainees from 14 programs in
      the SESAUA participated in the course and filled out a 1-page, 8-item
      questionnaire following their simulator exposure. RESULTS: Seventeen (53.1%)
      trainees, including 5 urology year-3 trainees, reported never having had robotic
      console time. Of the trainees, 65.6% (21 of 32) had access to the Mimic dV
      Trainer or Mimic "backpack" whereas 10 had no exposure to robotic simulation;
      84.4% (27 of 32) felt that the simulator replicated real-life robotic console
      surgery and 90.6% (29 of 32) felt the simulator was helpful or would be helpful
      for training in their program. Trainees felt the "tubes 2" drill, which mimics a
      vesicourethral anastomosis, was the most difficult drill to perform. CONCLUSIONS:
      A majority of trainees in the SESAUA have had limited to no robotic console time.
      A high number of resident trainees in the SESAUA have exposure to virtual reality
      robotic simulation. Trainees believe that the simulator replicates real-life
      robotic console movements and almost all believe they would be benefit from
      having access to robotic simulation.

PMID- 24016367
TI  - Current concepts of team training in surgical residency: a survey of North
      American program directors.
AB  - OBJECTIVES: The purpose of the present survey was to (1) establish the prevalence
      of Crew Resource Management (CRM)- and team-training interventions among general
      surgery residency programs of the United States and Canada; (2) to characterize
      current approaches to training and assessment of nontechnical skills; and (3) to
      inquire about program directors' (PDs') recommendations for future curricula in
      graduate medical education. DESIGN: An online questionnaire was developed by the
      authors and distributed via email to the directors of all accredited general
      surgery residency programs across the United States and Canada. After 3 email
      reminders, paper versions were sent to all nonresponders. PARTICIPANTS AND
      SETTING: PDs of accredited general surgery residency programs in the United
      States and Canada. RESULTS: One hundred twenty (47%) PDs from the United States
      and 9 (53%) from Canada responded to the survey. Of all respondents, 32% (n = 40)
      indicated conducting designated team-training interventions for residents. Three
      main instructional strategies were identified: combined approaches using
      simulation and didactic methods (42%, n = 16); predominantly simulation-based
      approaches (37%, n = 14); and didactic approaches (21%, n = 8). Correspondingly,
      83% (n = 93) of respondents recommended a combination of didactic methods and
      opportunities for practice for future curricula. A high agreement between
      responding PDs was shown regarding learning objectives for a proposed team-based
      training curriculum (alpha = 0.95). CONCLUSIONS: The self-reported prevalence of
      designated CRM- and team-training interventions among responding surgical
      residency programs was low. For the design of future curricula, the vast majority
      of responding PDs advocated for the combination of interactive didactic methods
      and opportunities for practice.

PMID- 24016368
TI  - Educational value of a preoperative CT sinus checklist: a resident's perspective.
AB  - OBJECTIVE: The objective of this study is to evaluate the educational value and
      effectiveness of a preoperative computed tomography (CT) sinus anatomy checklist
      as a teaching method from the perspective of otolaryngology residents. DESIGN:
      Between 2009 and 2011, 15 otolaryngology residents completed a CT sinus anatomy
      checklist prior to the start of sinus surgery cases. A cross-sectional brief
      Likert-type questionnaire assessed the resident experience with the checklist.
      Nine items explored its perceived utility, role in the preoperative setting,
      incorporation into practice, and recall. SETTING: St. Michael's Hospital,
      tertiary care hospital. PARTICIPANTS: Otolaryngology residents rotating through
      St. Michael's Hospital between 2009 and 2011 were enrolled into this study. A
      total of 15 residents entered and finished the study. RESULTS: Overall, all
      residents strongly agreed that the checklist was useful. It ensured that the CT
      imaging was properly reviewed and increased their comfort level with the relevant
      anatomy. Nearly all the residents continue to use this checklist even after
      completing the rotation with the senior author (JML). CONCLUSIONS: The CT sinus
      anatomy checklist was perceived as useful overall by otolaryngology residents. In
      the future, checklists should be applied to other areas of head and neck surgical
      training to further standardize preoperative planning.

PMID- 24016369
TI  - High-fidelity simulation-based team training in urology: evaluation of technical
      and nontechnical skills of urology residents during laparoscopic partial
      nephrectomy.
AB  - INTRODUCTION: The use of low-risk simulation training for resident education is
      rapidly expanding as teaching centers integrate simulation-based team training
      (SBTT) sessions into their education curriculum. SBTT is a valuable tool in
      technical and communication skills training and assessment for residents. We
      created a unique SBTT scenario for urology residents involving a laparoscopic
      partial nephrectomy procedure. MATERIALS AND METHODS: Urology residents were
      randomly paired with a certified registered nurse anesthetists or an anesthesia
      resident. The scenario incorporated a laparoscopic right partial nephrectomy
      utilizing a unique polyvinyl alcohol kidney model with an embedded 3cm lower pole
      exophytic tumor and the high-fidelity SimMan3G mannequin. The Urology residents
      were instructed to pay particular attention to the patient's identifying
      information provided at the beginning of the case. Two scripted events occurred,
      the patient had an anaphylactic reaction to a drug and, after tumor specimen was
      sent for a frozen section, the confederate pathologist called into the operating
      room (OR) twice, first with the wrong patient name and subsequently with the
      wrong specimen. After the scenario was complete, technical performance and
      nontechnical performance were evaluated and assessed. A debriefing session
      followed the scenario to discuss and assess technical performance and
      interdisciplinary nontechnical communication between the team. RESULTS: All
      Urology residents (n = 9) rated the SBTT scenario as a useful tool in developing
      communication skills among the OR team and 88% rated the model as useful for
      technical skills training. Despite cuing to note patient identification, only 3
      of 9 (33%) participants identified that the wrong patient information was
      presented when the confederate "pathologist" called in to report pathology
      results. CONCLUSION: All urology residents rated SBTT sessions as useful for the
      development of communication skills between different team members and making
      residents aware of unlikely but potential critical errors in the OR. We will
      continue to use SBTT as a useful method to develop resident technical and
      nontechnical skills outside of the high-risk operating environment.

PMID- 24016370
TI  - Laparoscopy training in surgical education: the utility of incorporating a
      structured preclinical laparoscopy course into the traditional apprenticeship
      method.
AB  - OBJECTIVE: To investigate whether preclinical laparoscopy training offers a
      benefit over standard apprenticeship training and apprenticeship training in
      combination with simulation training. DESIGN: This randomized controlled trial
      consisted of 3 groups of first-year surgical registrars receiving a different
      teaching method in laparoscopic surgery. SETTING: The KU LEUVEN Faculty of
      Medicine is the largest medical faculty in Belgium. PARTICIPANTS: Thirty final
      year medical students starting a general surgical career in the next academic
      year. METHODS: Thirty final-year medical students were randomized into 3 groups,
      which differed in the way they were exposed to laparoscopic simulation training
      but were comparable in regard to ambidexterity, sex, age, and laparoscopic
      psychomotoric skills. The control group received only clinical training during
      surgical residentship, whereas the interval group received clinical training in
      combination with simulation training. The registrars were allowed to do
      deliberate practice. The Centre for Surgical Technologies Preclinical Training
      Programme (CST PTP) group received a preclinical simulation course during the
      final year as medical students, but was not exposed to any extra simulation
      training during surgical residentship. At the beginning of surgical residentship
      and 6 months later, all subjects performed a standardized suturing task and a
      laparoscopic cholecystectomy in a POP Trainer. All procedures were recorded
      together with time and motion tracking parameters. All videos were scored by a
      blinded observer using global rating scales. RESULTS: At baseline the 3 groups
      were comparable. At 6 months, for suturing, the CST PTP group was better than
      both the other groups with respect to time, checklist, and amount of movements.
      The interval group was better than the control group on only the time and
      checklist score. For the cholecystectomy evaluation, there was a statistical
      difference between the CST PTP study group and both other groups on all
      evaluation scales in favor of the CST PTP group. CONCLUSIONS: Structured,
      preclinical proficiency-based training is better than clinical training combined
      with laboratory training or clinical training alone.

PMID- 24016371
TI  - Leadership in Canadian urology: what is the right stuff?
AB  - INTRODUCTION: There are little data characterizing leadership roles within
      Canadian Urology. The importance of these positions in urology underscores the
      need for further investigation to provide insight for recruitment, development,
      and success. METHODS: All Canadian Urology Program Directors and
      Division/Department Heads were invited to complete an online leadership survey as
      part of a larger national cohort from 11 other surgical specialties. RESULTS:
      Response rate was 62% (13/21), the majority of whom were Caucasian (77%) and male
      (92%). Only 8% of respondents in urology hold an advanced degree compared with
      45% in other specialties. Additional leadership training was done by 54% of the
      respondents. Residency was completed in Canada by 92%, but 62% completed
      fellowships abroad. A majority reported no well-defined job description for their
      role (54%). The top responsibility reported by leaders was mentoring residents
      (67%), followed by advising staff (62%). Excellence in patient care and teaching
      were seen as the most important professional characteristics, whereas integrity
      was the personal quality felt most important. Leaders reported 17% of their
      income came from their leadership role, equivalent to the time required for
      position duties (19%). "Time management" was listed as the greatest challenge
      faced (54%). Leadership style was reported as "democratic" by 92%. Leaders in
      urology most often self-rated their leadership skills lower than leaders from
      other surgical specialties (7 vs 8/10). CONCLUSION: Positions of leadership in
      urology are disproportionately represented by Caucasian males and comparatively
      few hold relevant advanced degrees. Excellence in the areas of teaching and
      patient care, and high personal integrity are felt to be the most important
      characteristics for success. Time management issues are viewed as the greatest
      challenge. These preliminary data may prove useful for the mentoring,
      recruitment, and success of future leaders in our specialty.

PMID- 24016372
TI  - Military and academic programs outperform community programs on the American
      Board of Surgery Examinations.
AB  - BACKGROUND: There is a paucity of American Board of Surgery (ABS) Qualifying
      Examination (QE) and Certifying Examination (CE) outcomes comparing residency
      programs by academic, community, or military affiliation. We hypothesize that the
      larger academic programs will outperform the smaller community programs. METHODS:
      In this retrospective study from 2002 to 2012, examination performance on the ABS
      QE and CE were obtained from the ABS for all of the general surgery residency
      programs. Programs were categorized by academic, community, and military
      affiliation. Both nonparametric and parametric statistics were used for
      comparison, using an alpha = 0.05. RESULTS: There were 137/235 (58.3%) academic
      programs, 90/235 (38.3%) community programs, and 8/235 (3.4%) military programs
      that satisfied inclusion criteria for this study. The Mann-Whitney U tests showed
      that the military programs outperformed academic and community programs on the
      ABS QE and the ABS CE, and had a higher proportion of examinees passing both
      examinations on the first attempt (all p<=0.02). One-tailed Student t-tests
      showed that academic programs had higher pass rates than community programs on
      the ABS QE (85.4%+/-9.5% vs. 81.9%+/-11.5%), higher pass rates on the ABS CE
      (83.6%+/-8.3% vs. 80.6%+/-11.0%), and a higher proportion of examinees passing
      both examinations on the first attempt (0.73+/-0.12 vs. 0.68+/-0.15) (all
      p<=0.01). The chi-square and Fisher exact tests showed that examinees performed
      highest in military programs, followed by academic programs, and lowest in
      community programs on the ABS QE and ABS CE (all p<= 0.01). CONCLUSIONS: Military
      programs have the highest degrees of success on all of the ABS examinations.
      Academic programs outperform community programs. These results have the potential
      to affect application patterns to established general surgery residency programs.

PMID- 24016373
TI  - Open surgical simulation--a review.
AB  - BACKGROUND: Surgical simulation has benefited from a surge in interest over the
      last decade as a result of the increasing need for a change in the traditional
      apprentice model of teaching surgery. However, despite the recent interest in
      surgical simulation as an adjunct to surgical training, most of the literature
      focuses on laparoscopic, endovascular, and endoscopic surgical simulation with
      very few studies scrutinizing open surgical simulation and its benefit to
      surgical trainees. The aim of this review is to summarize the current standard of
      available open surgical simulators and to review the literature on the benefits
      of open surgical simulation. CURRENT STATE OF OPEN SURGICAL SIMULATION: Open
      surgical simulators currently used include live animals, cadavers, bench models,
      virtual reality, and software-based computer simulators. In the current
      literature, there are 18 different studies (including 6 randomized controlled
      trials and 12 cohort studies) investigating the efficacy of open surgical
      simulation using live animal, bench, and cadaveric models in many surgical
      specialties including general, cardiac, trauma, vascular, urologic, and
      gynecologic surgery. The current open surgical simulation studies show, in
      general, a significant benefit of open surgical simulation in developing the
      surgical skills of surgical trainees. However, these studies have their
      limitations including a low number of participants, variable assessment
      standards, and a focus on short-term results often with no follow-up assessment.
      FUTURE OF OPEN SURGICAL SIMULATION: The skills needed for open surgical
      procedures are the essential basis that a surgical trainee needs to grasp before
      attempting more technical procedures such as laparoscopic procedures. In this
      current climate of medical practice with reduced hours of surgical exposure for
      trainees and where the patient's safety and outcome is key, open surgical
      simulation is a promising adjunct to modern surgical training, filling the void
      between surgeons being trained in a technique and a surgeon achieving fluency in
      that open surgical procedure. Better quality research is needed into the benefits
      of open surgical simulation, and this would hopefully stimulate further
      development of simulators with more accurate and objective assessment tools.

PMID- 24016374
TI  - Psychometric characteristics of the 360 degrees  feedback scales in
      professionalism and interpersonal and communication skills assessment of surgery
      residents in China.
AB  - AIMS: The aim of the study was to test the psychometric characteristics of the
      360 degrees  evaluation instrument for assessing residents' competency in
      professionalism, interpersonal and communication skills, and develop a feasible,
      valid, and reliable multisource feedback (MSF) program for surgery residents to
      address this gap. METHODS: We carried out an MSF assessment of 149 surgery
      residents at 19 hospitals all over China. MSF assessment includes 6 surveys with
      21, 21, 21, 26, 14, and 15 items and these surveys were developed to assess
      surgery residents by attending doctor, resident self, peer, nurse, patient, and
      office staff, respectively, using a 5-point agreement scale with an "unable-to
      evaluate" category. Reliability was assessed by Cronbach alpha. Exploratory
      factor analysis was used to assess validity and determine which items grouped
      together into scales. RESULTS: A total of 2384 questionnaires were analyzed in
      this study. The internal consistency reliability of the instruments was a
      Cronbach alpha of 0.932, 0.936, 0.914, 0.916, 0.939, and 0.903 for attending
      doctor, resident self, nurse, patient, resident peer, and office staff surveys,
      respectively. On the attending, resident self, resident peer, nurse, office
      staff, and patient surveys, the factor analysis identified 2 factors of
      professionalism and interpersonal and communication skills accounting for 75.62%,
      74.81%, 72.65%, 73.38%, 76.11%, and 63.89% of the variance, respectively. Some
      items, such as Demonstrates respect for my "Sexual Orientation," "Religion," and
      "Disability," in different surveys had high unable-to-evaluate rates (more than
      10%). CONCLUSIONS: The data suggest that these instruments developed to assess
      surgery residents are feasible to administer and provide valid and reliable
      evidence. Some items in survey need to be adjusted keeping in mind the Chinese
      culture.

PMID- 24016375
TI  - Small community hospitals programs affiliation with university programs; "lessons
      learned" in 28-year successful affiliation.
AB  - OBJECTIVE: Community hospitals affiliation with university hospitals in post
      graduate surgical education is essential for the 2 types of training programs.
      Many factors affect the success of the affiliation process. Additionally, various
      pitfalls and challenges are encountered. The goal of this work is to study the
      lessons learned in 28 years successful affiliation. DESIGN/SETTING: small
      community hospital affiliation with university program for 28 years.
      PARTICIPANTS: surgery residency programs in small community hospital and
      university hospital. RESULTS: successful affiliation for 28 years between
      community hospital and university program.

PMID- 24016376
TI  - Spouses of thoracic surgery applicants: changing demographics and motivations in
      a new generation.
AB  - INTRODUCTION: Applications to thoracic residency have decreased. The causes are
      multifactorial, but include changing motivations such as lifestyle concerns.
      Thoracic residents (TRs) have been well studied, but no one has ever
      characterized the influence or motivations of their spouses. We sought to
      evaluate the demographics and interests of TR spouses. METHODS: An electronic
      survey was sent to all TR applicants over 2 years at 2 training programs and to
      all current TRs in 2010. Recipients were asked to forward the survey to their
      spouses. Responses were analyzed globally and compared in subgroups. RESULTS:
      Sixty-six surveys were completed and returned for a response rate of 19%. Among
      them, 86% of respondents were female, with 82% being married for a mean of 4.3
      years. Fifty-nine percent of respondents had children and 64% were planning on
      having more children within 3 years. Hundred percent felt optimistic that they
      would be financially stable after training, but only 57% were optimistic about
      quality of life after training. Eighty-four percent felt that they had influence
      on the choice of training program. Almost 80% wanted more information on salary,
      housing, and access to faculty spouses. Quality of fellowship, geographic
      location, and proximity to family were the top 3 factors in choosing a program.
      CONCLUSIONS: Nearly 90% of respondents reported they want to travel to more
      interviews, and nearly 90% of respondents reported having some to complete
      influence over which training program to attend. It is safe to presume,
      therefore, that applicant spouses are not only highly influential on TR
      applicants but also interested in greater inclusion in the interview process. The
      results show numerous demographic and characteristic trends which, if further
      validated by definitive studies, would be applicable to all post-surgery
      residency training programs and may help TR programs to be more competitive in
      attracting applicants and their families.

PMID- 24016377
TI  - Surgeons' attitude toward a competency-based training and assessment program:
      results of a multicenter survey.
AB  - BACKGROUND: Currently, most surgical training programs are focused on the
      development and evaluation of professional competencies. Also in the Netherlands,
      competency-based training and assessment programs were introduced to restructure
      postgraduate medical training. The current surgical residency program is based on
      the Canadian Medical Education Directives for Specialists (CanMEDS) competencies
      and uses assessment tools to evaluate residents' competence progression. In this
      study, we examined the attitude of surgical residents and attending surgeons
      toward a competency-based training and assessment program used to restructure
      general surgical training in the Netherlands in 2009. METHODS: In 2011, all
      residents (n = 51) and attending surgeons (n = 108) in 1 training region,
      consisting of 7 hospitals, were surveyed. Participants were asked to rate the
      importance of the CanMEDS competencies and the suitability of the adopted
      assessment tools. Items were rated on a 5-point Likert scale and considered
      relevant when at least 80% of the respondents rated an item with a score of 4 or
      5 (indicating a positive attitude). Reliability was evaluated by calculating the
      Cronbach's alpha, and the Mann-Whitney test was applied to assess differences
      between groups. RESULTS: The response rate was 88% (n = 140). The CanMEDS
      framework demonstrated good reliability (Cronbach's alpha = 0.87). However, the
      importance of the competencies 'Manager' (78%) and 'Health Advocate' (70%) was
      undervalued. The assessment tools failed to achieve an acceptable reliability
      (Cronbach's alpha = 0.55), and individual tools were predominantly considered
      unsuitable for assessment. Exceptions were the tools 'in-training evaluation
      report' (91%) and 'objective structured assessment of technical skill' (82%). No
      significant differences were found between the residents and the attending
      surgeons. CONCLUSION: This study has demonstrated that, 2 years after the reform
      of the general surgical residency program, residents and attending surgeons in a
      large training region in the Netherlands do not acknowledge the importance of all
      CanMEDS competencies and consider the assessment tools generally unsuitable for
      competence evaluation.

PMID- 24016378
TI  - The cost of intraoperative plastic surgery education.
AB  - PURPOSE: Within the surgical community, it is commonly accepted that the length
      and cost of a surgical case increase when a resident physician participates. Many
      accountable care organizations, however, believe the opposite, that is, resident
      assistance enhances efficiency and diminishes operative time. The purpose of this
      study is to determine the opportunity cost to the attending surgeon for
      intraoperative teaching during index plastic surgery cases. METHODS: A single
      senior surgeon's experience over a 7-year period was evaluated retrospectively
      for Current Procedural Terminology codes 40700 (repair of primary, unilateral
      cleft lip) and 42200 (palatoplasty). Variables collected include operative time,
      the presence or absence of a physician learner, and postgraduate year level.
      Statistical analysis was performed with the Kruskal-Wallis test using the S+
      programming language. A cost analysis was performed to quantify the effect of
      longer operative times in terms of relative value units (RVUs) lost. RESULTS:
      During the study period, a total of 45 patients had primary, unilateral cleft lip
      repair; 70 patients had cleft palate repair. Of those cases, 39 (87%) cleft lip
      repairs and 60 (86%) cleft palate repairs were performed with a resident or
      fellow present. There was a statistically significant difference in the amount of
      time required to perform either surgery with a physician learner than without,
      with operative times being 60% (p = 0.020) longer for cleft lip repair and 65% (p
      = 0.0016) longer for cleft palate repair. The results were further stratified
      based on level of training, with craniofacial fellows and plastic surgery
      residents (independent and integrated) compared separately. Cases where a
      craniofacial fellow was present required the longest operative times: 103% (p =
      0.0012) longer for cleft lip repairs and 104% (p < 0.0001) longer for cleft
      palate repairs when compared with the senior surgeon operating alone. Using the
      2011 physician work RVUs for these surgeries and the 2011 Medicare conversion
      factor for RVUs to dollars, the opportunity cost is over $275 per case per
      trainee for any physician learner. When craniofacial fellows are analyzed
      separately, over $440 is invested in intraoperative teaching per case per fellow.
      CONCLUSIONS: Resident involvement in the operating room is crucial to the
      education of independent surgeons. This involvement, however, comes at a
      significant opportunity cost to the attending surgeon. As an incentive to retain
      academic surgeons and uphold a quality academic environment in the OR,
      compensation should be offered for intraoperative teaching.

PMID- 24016379
TI  - The incidence and reporting of sharps exposure among medical students, orthopedic
      residents, and faculty at one institution.
AB  - OBJECTIVE: To compare the incidence of sharps injuries among medical students,
      orthopedic residents/fellows, and orthopedic faculty at one institution and to
      determine the rate of reporting exposures. DESIGN: Cross-sectional survey.
      Surveys were completed by 44% (53/120) of medical students, 76% (23/30) of
      residents/fellows, and 56% (17/30) of full-time faculty. SETTING: Academic
      medical center. PARTICIPANTS: Medical students, orthopedic surgery
      residents/fellows, full-time academic orthopedic surgery faculty. RESULTS: Twenty
      eight percent of medical students, 83% of residents/fellows, and 100% of faculty
      had been exposed to a sharps injury at some point in their career; 42% of
      residents/fellows had experienced a sharps exposure within the past year. The
      most common single instrument responsible for sharps injuries among all groups
      was the solid-bore needle; students and residents were significantly more likely
      than faculty to have a sharps injury from a solid-bore needle than all other
      devices combined (p = 0.04). Medical students were more likely to ignore the
      exposure than residents/fellows (p = 0.004) or faculty (p = 0.036). Only 12.5% of
      medical students followed all the steps of the postexposure protocol. CONCLUSION:
      Sharps exposures occur among orthopedic surgeons and their trainees.
      Interventions are needed to increase safety among residents and medical students.
      Further research should evaluate factors suppressing medical student reporting of
      sharps exposures.

PMID- 24016380
TI  - The "July effect" does not have clinical relevance in liver transplantation.
AB  - In the beginning of the academic year, medical errors are often attributed to
      inexperienced medical staff. This potential seasonal influence on health care
      outcomes is termed the "July effect." No study has demonstrated the July effect
      in liver transplantation. We reviewed retrospectively collected data from the
      United Network for Organ Sharing for patients who underwent liver transplantation
      from October 1987 to June 2011 to determine if surgical outcomes were worse in
      July compared with rest of the year. We found no clinical difference in early
      graft survival (91.11% vs. 90.72%, p = 0.045) and no difference in early patient
      survival (94.71% vs. 94.42%, p = 0.057). Survival at 1 year, 3 years, and 5 years
      was also compared and no notable differences were detected. Because the Model for
      End-stage Liver Disease (MELD) score implementation in 2002 affected the acuity
      of liver transplant recipients, we further stratified our data to compare pre-
      and post-MELD survival to remove subjectivity as a confounding factor. MELD
      stratification revealed no seasonal difference in outcomes. There was no
      difference in rate of graft failure and acute and chronic rejection between
      groups. Our findings show no evidence of the July effect in liver
      transplantation. Each July, thousands of medical residents take on new
      responsibilities in patient care. It has been suggested that these new
      practitioners may produce errors that contribute to worse patient outcomes in the
      beginning of the academic year-a phenomenon called the "July effect." Currently,
      there are few research studies with controversial evidence of poorer outcomes in
      July, and no articles address the effect of new medical staff in the setting of
      liver transplantation. Our study compares short-, medium-, and long-term graft
      and patient survival between July and August and the remaining months using
      national data. We also examine survival before and after the implementation of
      the MELD scoring system to determine its effect on outcomes in the beginning of
      the academic year.

PMID- 24016381
TI  - Surgical leadership through coaching.

PMID- 24016382
TI  - Response inhibition in alcohol-dependent patients and patients with
      depression/anxiety: a functional magnetic resonance imaging study.
AB  - BACKGROUND: The inability to inhibit certain behaviors is a key feature of
      impulsivity, which is often present in people with a substance use disorder.
      However, the findings on impulsivity in people with alcohol dependence (AD) are
      inconsistent, possibly because of the frequent co-occurrence of
      depression/anxiety (D/A) and its influence on impulsivity. In the current study,
      we aimed to distinguish response inhibition impairments in AD from possible
      response inhibition effects associated with D/A. METHOD: AD patients (n = 31)
      with high D/A co-morbidity were compared to patients with D/A only (n = 18) and
      healthy controls (HCs; n = 16) using the Stop Signal Task (SST) during functional
      magnetic resonance imaging (fMRI). Correlation analyses were performed between
      activated brain areas, behavioral data and addiction and D/A characteristics.
      RESULTS: The three groups did not differ on response inhibition performance.
      However, AD severity, but not D/A severity, was positively associated with
      decreased response inhibition. During the SST, AD patients showed hyperactivity
      in the putamen and thalamus compared with D/A patients and HCs. Thalamus
      activation was negatively associated with AD duration. In addition, AD patients
      showed hypoactivity in the supplementary motor area (SMA) compared with HCs. SMA
      activity within HCs was negatively correlated with depressive symptom severity.
      Discussion In general, AD patients were not more impulsive than D/A patients or
      HCs but they did reveal inhibition impairments with increasing AD severity. A
      shift from cortical to subcortical engagement in AD patients during response
      inhibition may represent an alternative strategy, which decreased with longer
      drinking history, suggesting the presence of an AD-specific endophenotype.

PMID- 24016383
TI  - A patient with multiple episodes of rhabdomyolysis induced by different
      neuroleptics.

PMID- 24016384
TI  - Behavioral factors and hospital admissions/readmissions in patients with CHF.
AB  - BACKGROUND: Wasted health care resources have become a central concern in
      American health care. Heart failure has one of the highest readmission rates
      amongst all conditions studied in Medicare/Medicaid populations. OBJECTIVE: The
      present study was an attempt to cross-sectionally identify correlates of number
      of past-year admissions and 30-day readmissions in patients with congestive heart
      failure. METHODS: Eighty-four patients with congestive heart failure were
      recruited during hospitalization and underwent a semistructured interview for
      basic clinical/demographic information and completed several questionnaires
      measuring depression, anxiety, and spirituality. RESULTS: Depression, history of
      substance abuse, and history of coronary artery disease displayed borderline
      results as correlates of past-year admissions. Immediate memory and psychiatric
      history (positive Patient Health Questionnaire 9, acknowledged history of
      treatment, and use of an antidepressant per chart) were associated with 30-day
      readmission rates. Indices of congestive heart failure severity (ejection
      fraction and last recorded B-type natriuretic peptide level) were not.
      CONCLUSIONS: Present results suggest that both a psychiatric history and
      cognitive impairment are possible determinants of early readmission.

PMID- 24016385
TI  - The effect of testosterone levels on mood in men: a review.
AB  - BACKGROUND: The effects of both high and low levels of testosterone are wide
      ranging and can include changes in mood, often overlapping with symptoms of mood
      disorders. OBJECTIVE: We sought to review the literature on the correlation of
      high and low levels of testosterone on mood disorders in men. RESULTS: Based on
      limited studies, high levels of testosterone are related to increased rates of
      depression as well as hypomania, whereas low levels of testosterone are related
      to depressive disorders in certain subpopulations of patients. There is
      insufficient evidence to conclude that low testosterone level routinely leads to
      major depressive disorder in men. CONCLUSIONS: Physicians should consider
      screening for low testosterone levels in certain subgroups of depressed men.

PMID- 24016386
TI  - Pd-catalyzed Heck-type cascade reactions with N-tosyl hydrazones: an efficient
      way to alkenes via in situ generated alkylpalladium.
AB  - A palladium-catalyzed Heck-type cascade reaction of aryl halides and N-tosyl
      hydrazones is reported. The neopentylpalladium species, generated from an
      intramolecular Heck-type insertion reaction of aryl halides, could efficiently
      react with carbenes to form highly functionalized alkenes. The synthesis of spiro
      compounds was also explored via a multiple Heck-type insertion reaction with N
      tosyl hydrazone. 

PMID- 24016387
TI  - Papillomavirus associated diseases of the horse.
AB  - The Papillomaviridae family comprises a large number of viruses that can infect a
      broad range of hosts including mammals, birds and reptiles giving rise to benign
      lesions of the skin or mucosal membranes. They are characterized by great genetic
      diversity yet adhere to common biological principles. In this review, we first
      describe the structure and function of the viral proteins encoded by
      papillomaviruses (PVs), with a particular emphasis on bovine papillomaviruses
      (BPV). We then discuss the role of BPV types 1 and 2 in the pathogenesis of
      equine sarcoids and present recent evidence implicating a novel equine
      papillomavirus (EcPV-2) in the pathogenesis of equine genital cancers. 

PMID- 24016388
TI  - Clinical significance of autoantibodies in autoimmune hepatitis.
AB  - The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon
      the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA)
      and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1),
      whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol
      type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti
      LKM1, have also been detected in de-novo autoimmune hepatitis developing after
      liver transplantation, a condition that may affect patients transplanted for non
      autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are
      also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome,
      referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary
      sclerosing cholangitis, is often associated with atypical perinuclear anti
      neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected
      in other autoimmune liver diseases. These associations highlight the necessity
      for simple and prompt diagnostic autoantibody testing, and the requirement for
      the accurate interpretation of the results of the tests in the clinical context.
      Fine-mapping of antigenic autoantibody targets has facilitated the development of
      rapid molecular assays that have the potential to revolutionise the field if
      properly standardised and when used in combination with classical
      immunofluorescence. Despite their diagnostic significance, the pathogenic role of
      the various autoantibodies and the mechanisms by which they can potentially
      inflict damage onto the liver cell remain a topic for further research. 

PMID- 24016389
TI  - Nanolithography on graphene by using scanning tunneling microscopy in a methanol
      environment.
AB  - Since it was discovered in 2004, graphene has attracted enormous attention as an
      emerging material for future devices, but it has been found that conventional
      lithographic processes based on polymer resist degrade its intrinsic performance.
      Recently, our group studied a resist-free scanning tunneling microscopy-based
      lithography in various atmospheres by injecting volatile liquids into a chamber.
      In this study, multilayer graphene was scanned and etched by controlling bias
      voltage under methanol pressure. We focused on improving patterning results in
      terms of depth and line width, while the previous study was performed to find an
      optimum gas environment for patterning on a graphite surface. Specifically, we
      report patterning outputs depending on conditions of voltage, current, and
      pressure. The optimum conditions for methanol environment etching were a gas
      pressure in the range of 41-50 torr, a -4 V tip bias, and a 2 nA tunneling
      current. 

PMID- 24016390
TI  - Impact of atypical long-acting injectable versus oral antipsychotics on
      rehospitalization rates and emergency room visits among relapsed schizophrenia
      patients: a retrospective database analysis.
AB  - BACKGROUND: Among schizophrenia patients relapsed on an oral antipsychotic (AP),
      this study compared the impact of switching to atypical AP long-acting injectable
      therapy (LAT) versus continuing oral APs on hospitalization and emergency room
      (ER) visit recurrence. METHODS: Electronic records from the Premier Hospital
      Database (2006-2010) were analyzed. Adult patients receiving oral APs during a
      schizophrenia-related hospitalization were identified and, upon relapse (i.e.,
      rehospitalization for schizophrenia), were stratified into (a) patients switching
      to atypical LAT and (b) patients continuing with oral APs. Atypical LAT relapse
      patients were matched 1:3 with oral AP relapse patients, using a propensity score
      model. Andersen-Gill Cox proportional hazards models assessed the impact of
      atypical LAT versus oral AP on time to multiple recurrences of all-cause
      hospitalizations and ER visits. No adjustment was made for multiplicity. RESULTS:
      Atypical LAT (N = 1032) and oral AP (N = 2796) patients were matched and well
      balanced with respect to demographic (mean age: 42.1 vs 42.4 years, p = .5622;
      gender: 43.6% vs 44.6% female, p = .5345), clinical, and hospital
      characteristics. Over a mean 30-month follow-up period, atypical LATs were
      associated with significantly lower mean number of rehospitalizations (1.25 vs
      1.61, p < .0001) and ER visits (2.33 vs 2.67, p = .0158) compared with oral APs,
      as well as fewer days in hospital (mean days: 13.46 vs. 15.69, p = .0081).
      Rehospitalization (HR 0.81, 95% CI 0.76-0.87, p < .0001) and ER visit (HR 0.88,
      95% CI 0.87-0.93, p < .0001) rates were significantly lower for patients
      receiving atypical LAT versus oral APs. CONCLUSIONS: This hospital database
      analysis found that in relapsed schizophrenia patients, atypical LATs were
      associated with lower rehospitalization and ER visit rates than oral APs.

PMID- 24016391
TI  - Transonic, thermodilution, or ionic dialysance to manage vascular access: which
      method is best?
AB  - Regularly monitoring blood flow through a vascular access (Qa) can predict a
      dysfunction and dramatically reduce the number of thromboses. The aim of our
      study was to compare two integrated access flow devices, thermodilution (Qa-BTM:
      BTM((r)), Fresenius Medical Care, Bad Homburg, Germany) and ionic dialysance (Qa
      ID: OCM((r)), Fresenius Medical Care, Bad Homburg, Germany), with the "gold
      standard" saline dilution (Qa-T: Transonic((r)), Systems Inc., Ithaca, NY, USA).
      Measurements were performed sequentially and were repeated in the first 90
      minutes of a single dialysis session in 24 long-term hemodialysis patients with a
      vascular access. Bland-Altman, linear regression (r(2)), and intraclass
      correlation coefficients (ICC) assessed reproducibility, correlations, and
      concordance between the techniques. Average access flow for Qa-T was 1549 (+/-
      844) mL/minute, Qa-BTM was 1530 (+/- 856) mL/minute (P = NS), and Qa-ID was 1619
      (+/- 1085) mL/minute (P = NS). Respectively, ICC, (r(2)), and bias were 0.99,
      (0.98), and -19 mL/minute for Qa-BTM, and 0.75, (0.65), and +69 mL/minute for Qa
      ID. The limits of agreement were -287 to +250 mL/minute for Qa-BTM and -1647 to
      +1785 mL/minute for Qa-ID. Reproducibility of thermodilution and ionic
      dialysance, expressed as relative differences, was not significantly different
      from saline dilution. Recirculation, measured by saline dilution, was 0% (0-4%),
      the same as the 0% measured by thermodilution, with correct placement of
      bloodlines and corrected for cardiopulmonary recirculation. The integrated access
      flow measurement devices, thermodilution and ionic dialysance, are reasonable
      alternatives to using saline dilution to measure Qa: Thermodilution showed better
      precision and correlation. They are reliable, make monitoring of vascular access
      easier, incur no extra costs, and use no additional consumables.

PMID- 24016392
TI  - MicroRNAs: regulators of cancer metastasis and epithelial-mesenchymal transition
      (EMT).
AB  - Tumor metastasis is the main cause of death in patients with solid tumors. The
      epithelial-mesenchymal transition (EMT) process, in which epithelial cells are
      converted into mesenchymal cells, is frequently activated during cancer invasion
      and metastasis. MicroRNAs (miRNAs) are small, non-coding RNAs that provide
      widespread expressional control by repressing mRNA translation and inducing mRNA
      degradation. The fundamental roles of miRNAs in tumor growth and metastasis have
      been increasingly well recognized. A growing number of miRNAs are reported to
      regulate tumor invasion/metastasis through EMT-related and/or non-EMT- related
      mechanisms. In this review, we discuss the functional role and molecular
      mechanism of miRNAs in regulating cancer metastasis and EMT.

PMID- 24016393
TI  - Subcurative radiation significantly increases cell proliferation, invasion, and
      migration of primary glioblastoma multiforme in vivo.
AB  - Tumor cell proliferation, infiltration, migration, and neovascularization are
      known causes of treatment resistance in glioblastoma multiforme (GBM). The
      purpose of this study was to determine the effect of radiation on the growth
      characteristics of primary human GBM developed in a nude rat. Primary GBM cells
      grown from explanted GBM tissues were implanted orthotopically in nude rats.
      Tumor growth was confirmed by magnetic resonance imaging on day 77 (baseline)
      after implantation. The rats underwent irradiation to a dose of 50 Gy delivered
      subcuratively on day 84 postimplantation (n = 8), or underwent no radiation (n =
      8). Brain tissues were obtained on day 112 (nonirradiated) or day 133
      (irradiated). Immunohistochemistry was performed to determine tumor cell
      proliferation (Ki-67) and to assess the expression of infiltration marker (matrix
      metalloproteinase-2, MMP-2) and cell migration marker (CD44). Tumor
      neovascularization was assessed by microvessel density using von-Willebrand
      factor (vWF) staining. Magnetic resonance imaging showed well-developed,
      infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67
      positive cells in tumors undergoing radiation was (71 +/- 15)% compared with (25
      +/- 12)% in the nonirradiated group (P = 0.02). The number of MMP-2-positive
      areas and proportion of CD44-positive cells were also high in tumors receiving
      radiation, indicating great invasion and infiltration. Microvessel density
      analysis did not show a significant difference between nonirradiated and
      irradiated tumors. Taken together, we found that subcurative radiation
      significantly increased proliferation, invasion, and migration of primary GBM.
      Our study provides insights into possible mechanisms of treatment resistance
      following radiation therapy for GBM. 

PMID- 24016394
TI  - Long-term outcome and late toxicities of simultaneous integrated boost-intensity
      modulated radiotherapy in pediatric and adolescent nasopharyngeal carcinoma.
AB  - The application of simultaneous integrated boost-intensity modulated radiotherapy
      (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is
      underevaluated. This study aimed to evaluate long-term outcome and late
      toxicities in pediatric and adolescent NPC after SIB-IMRT combined with
      chemotherapy. Thirty-four patients (aged 8-20 years) with histologically proven,
      non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective
      study. The disease stage distribution was as follows: stage I, 1 (2.9%); stage
      III, 14 (41.2%); and stage IV, 19 (55.9%). All patients underwent SIB-IMRT and 30
      patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT
      was 64-68 Gy in 29-31 fractions to the nasopharyngeal gross target volume. Within
      the median follow-up of 52 months (range, 9-111 months), 1 patient (2.9%)
      experienced local recurrence and 4 (11.8%) developed distant metastasis (to the
      lung in 3 cases and to multiple organs in 1 case). Four patients (11.8%) died due
      to recurrence or metastasis. The 5-year locoregional relapse-free survival,
      distant metastasis-free survival, disease-free survival, and overall survival
      rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute
      toxicities were grades 3-4 hematologic toxicities and stomatitis. Of the 24
      patients who survived for more than 2 years, 16 (66.7%) and 15 (62.5%) developed
      grades 1-2 xerostomia and ototoxicity, respectively. Two patients (8.3%)
      developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT
      combined with chemotherapy achieves excellent long-term locoregional control in
      pediatric and adolescent NPC, with mild incidence of late toxicities. Distant
      metastasis is the predominant mode of failure. 

PMID- 24016395
TI  - Computer-aided design, synthesis, and biological evaluation of 5- substituted
      aminomethylenepyrimidine-2,4,6-triones as H1 antihistaminic agents (Part2).
AB  - As a part of a research project pertaining to the synthesis of novel candidates
      as nonsedating, nonclassic H1 histaminergic (H1) blockers with low toxicity
      profiles, some new 5-substituted aminomethylenepyrimidine-2,4,6-triones were
      designed based on the H1 histaminic receptor pharmacophore model. The
      interactions between the designed compounds and the H1 receptor were studied
      using molecular docking on the homology model of H1 receptor. The designed
      compounds were synthesized and biologically evaluated for H1-blocking activity;
      using isolated segments of guinea pig ileum. Compounds 15,18,19 and 21 exhibited
      comparable activities to acrivastine (22) as reference nonsedating drug. The C
      log P of designed compounds revealed lower values in reference to acrivastine
      (22) which might indicate decreased tendency for crossing the blood brain
      barrier.

PMID- 24016397
TI  - [Hyponatremia and asthenia in a 76-year-old patient].

PMID- 24016398
TI  - Task based rehabilitation protocol for elite athletes following Anterior Cruciate
      ligament reconstruction: a clinical commentary.
AB  - Anterior Cruciate ligament (ACL) injuries are one of the most common and
      devastating knee injuries sustained whilst participating in sport. ACL
      reconstruction (ACLR) remains the standard approach for athletes who aim to
      return to high level sporting activities but the outcome from surgery is not
      assured. Secondary morbidities and an inability to return to the same competitive
      level are common following ACLR. One factor which might be linked to these sub
      optimal outcomes may be a failure to have clearly defined performance criteria
      for return to activity and sport. This paper presents a commentary describing a
      structured return to sport rehabilitation protocol for athletes following ACLR.
      The protocol was developed from synthesis of the available literature and
      consensus of physiotherapists and strength and conditioning coaches based in the
      home country Institute of Sports within the United Kingdom.

PMID- 24016396
TI  - Prevalence of antibodies to Sarcocystis neurona and Neospora hughesi in horses
      from Mexico.
AB  - Equine protozoal myeloencephalitis (EPM) is a debilitating disease of horses
      caused by Sarcocystis neurona and Neospora hughesi. Sera from 495 horses in
      Durango State, Mexico were tested for anti-protozoal antibodies using enzyme
      linked immunosorbent assays (ELISAs) based on major surface antigens of these two
      parasites. Antibodies to S. neurona were detected in 240 (48.5%) of the 495 horse
      sera tested with the rSnSAG2/4/3 trivalent ELISA. Multivariate analysis showed
      that exposure to S. neurona was associated with age, feeding grains and crops,
      and small herd size. Antibodies to N. hughesi were found in 15 (3.0%) of the 495
      horse sera tested with the rNhSAG1 ELISA and confirmed by Western blot of N.
      hughesi tachyzoite antigen. This is the first report of S. neurona and N. hughesi
      exposure in horses in Mexico, and it affirms that EPM should be in the
      differential diagnosis for horses exhibiting signs of neurologic disease in this
      country. 

PMID- 24016399
TI  - Increased impact factor for Physical Therapy in Sport.

PMID- 24016400
TI  - Experiential knowledge of expert coaches can help identify informational
      constraints on performance of dynamic interceptive actions.
AB  - Coordination of dynamic interceptive movements is predicated on cyclical
      relations between an individual's actions and information sources from the
      performance environment. To identify dynamic informational constraints, which are
      interwoven with individual and task constraints, coaches' experiential knowledge
      provides a complementary source to support empirical understanding of performance
      in sport. In this study, 15 expert coaches from 3 sports (track and field,
      gymnastics and cricket) participated in a semi-structured interview process to
      identify potential informational constraints which they perceived to regulate
      action during run-up performance. Expert coaches' experiential knowledge revealed
      multiple information sources which may constrain performance adaptations in such
      locomotor pointing tasks. In addition to the locomotor pointing target, coaches'
      knowledge highlighted two other key informational constraints: vertical reference
      points located near the locomotor pointing target and a check mark located prior
      to the locomotor pointing target. This study highlights opportunities for
      broadening the understanding of perception and action coupling processes, and the
      identified information sources warrant further empirical investigation as
      potential constraints on athletic performance. Integration of experiential
      knowledge of expert coaches with theoretically driven empirical knowledge
      represents a promising avenue to drive future applied science research and
      pedagogical practice.

PMID- 24016401
TI  - Community integration after traumatic brain injury: a systematic review of the
      clinical implications of measurement and service provision for older adults.
AB  - OBJECTIVE: To explore the scope, reliability, and validity of community
      integration measures for older adults after traumatic brain injury (TBI). DATA
      SOURCES: A search of peer-reviewed articles in English from 1990 to April 2011
      was conducted using the EBSCO Health and Scopus databases. Search terms included
      were community integration, traumatic brain injury or TBI, 65 plus or older
      adults, and assessment. STUDY SELECTION: Forty-three eligible articles were
      identified, with 11 selected for full review using a standardized critical review
      method. DATA EXTRACTION: Common community integration measures were identified
      and ranked for relevance and psychometric properties. Of the 43 eligible
      articles, studies reporting community integration outcomes post-TBI were
      identified and critically reviewed. Older adults' community integration needs
      post-TBI from high quality studies were summarized. DATA SYNTHESIS: There is a
      relative lack of evidence pertaining to older adults post-TBI, but indicators are
      that older adults have poorer outcomes than their younger counterparts. The
      Community Integration Questionnaire (CIQ) is the most widely used community
      integration measurement tool used in research for people with TBI. Because of
      some limitations, many studies have used the CIQ in conjunction with other
      measures to better quantify and/or monitor changes in community integration.
      CONCLUSIONS: Enhancing integration of older adults after TBI into their community
      of choice, with particular emphasis on social integration and quality of life,
      should be a primary rehabilitation goal. However, more research is needed to
      inform best practice guidelines to meet the needs of this growing TBI population.
      It is recommended that subjective tools, such as quality of life measures, are
      used in conjunction with well-established community integration measures, such as
      the CIQ, during the assessment process.

PMID- 24016402
TI  - Association between the volume of inpatient rehabilitation therapy and the risk
      of all-cause and cardiovascular mortality in patients with ischemic stroke.
AB  - OBJECTIVE: To investigate the relationship between the volume of inpatient
      rehabilitation therapy and mortality among patients with acute ischemic stroke,
      as well as to assess whether the association varies with respect to stroke
      severity. DESIGN: A retrospective study with a cohort of consecutive patients who
      had acute ischemic stroke between January 1, 2008, and June 30, 2009. SETTING:
      Referral medical center. PARTICIPANTS: Adults with acute ischemic stroke (N=1277)
      who were admitted to a tertiary hospital. INTERVENTIONS: Not applicable. MAIN
      OUTCOME MEASURE: Stroke-related mortality. RESULTS: During the median follow-up
      period of 12.3 months (ranging from January 1, 2008, to December 31, 2009), 163
      deaths occurred. Greater volume of rehabilitation therapy was associated with a
      reduced risk of all-cause and cardiovascular mortality (P for trend <.001 for
      both). Compared with the first tertile, the third tertile of rehabilitation
      volume was associated with a 55% lower risk of all-cause mortality (hazard ratio
      [HR]=.45; 95% confidence interval [CI], .30-.65) and a 50% lower risk of
      cardiovascular mortality (HR=.50; 95% CI, .31-.82). The association did not vary
      with respect to stroke severity (P for interaction = .45 and .73 for all-cause
      and cardiovascular mortality, respectively). CONCLUSIONS: The volume of inpatient
      rehabilitation therapy and mortality were significantly inversely related in the
      patients with ischemic stroke. Thus, further programs aimed at promoting greater
      use of rehabilitation services are warranted.

PMID- 24016403
TI  - Comparison of metabolic cost, performance, and efficiency of propulsion using an
      ergonomic hand drive mechanism and a conventional manual wheelchair.
AB  - OBJECTIVE: To compare the metabolic cost (oxygen uptake per unit time [Vo2
      consumption], heart rate, and number of pushes), performance (velocity and
      distance traveled), and efficiency (oxygen uptake per distance traveled [Vo2
      efficiency]) of propulsion using a novel ergonomic hand drive mechanism (EHDM)
      and a conventional manual wheelchair (CMW). DESIGN: Repeated-measures crossover
      design. SETTING: Semicircular track. PARTICIPANTS: Adult full-time manual
      wheelchair users with spinal cord injuries (N=12; mean age +/- SD, 38.8+/-12.4y;
      mean body mass +/- SD, 73.7+/-13.3kg; mean height +/- SD, 173.6+/-11.1cm) who
      were medically and functionally stable and at least 6 months postinjury.
      INTERVENTION: Participants propelled themselves for 3.5 minutes at a self
      selected pace in a CMW and in the same chair fitted with the EHDM. MAIN OUTCOME
      MEASURES: Velocity, distance traveled, number of pushes, Vo2 consumption, Vo2
      efficiency, and heart rate were compared by wheelchair condition for the last 30
      seconds of each trial using paired t tests (alpha=.01). RESULTS: The CMW
      condition resulted in more distance traveled (33.6+/-10.8m vs 22.4+/-7.8m;
      P=.001), greater velocity (1.12+/-0.4m/s vs .75+/-.30m/s; P=.001), and better Vo2
      efficiency (.10+/-.03mL.kg(-1).m(-1) vs .15+/-.03mL.kg(-1).m(-1); P<.001) than
      the EHDM condition, respectively. No significant differences were found between
      the 2 conditions for number of pushes (27.5+/-5.7 vs 25.7+/-5.4; P=.366), Vo2
      consumption (6.43+/-1.9mL.kg(-1).min(-1) vs 6.19+/-1.7mL.kg(-1).min(-1); P=.573),
      or heart rate (100.5+/-14.5 beats per minute vs 97.4+/-20.2 beats per minute;
      P=.42). CONCLUSIONS: The results demonstrate that metabolic costs did not differ
      significantly; however, performance and efficiency were sacrificed with the EHDM.
      Modifications to the EHDM (eg, addition of gearing) could rectify the performance
      and efficiency decrements while maintaining similar metabolic costs. Although not
      an ideal technology, the EHDM can be considered as an alternative mode of
      mobility by wheelchair users and rehabilitation specialists.

PMID- 24016404
TI  - Comparative analysis of the Trichoderma reesei transcriptome during growth on the
      cellulase inducing substrates wheat straw and lactose.
AB  - BACKGROUND: Renewable lignocellulosic biomass is an advantageous resource for the
      production of second generation biofuels and other biorefinery products. In
      Middle Europe, wheat straw is one of the most abundant low-cost sources of
      lignocellulosic biomass. For its efficient use, an efficient mix of cellulases
      and hemicellulases is required. In this paper, we investigated how cellulase
      production by T. reesei on wheat straw compares to that on lactose, the only
      soluble and also cheap inducing carbon source for enzyme production. RESULTS: We
      have examined and compared the transcriptome of T. reesei growing on wheat straw
      and lactose as carbon sources under otherwise similar conditions. Gene expression
      on wheat straw exceeded that on lactose, and 1619 genes were found to be only
      induced on wheat straw but not on lactose. They comprised 30% of the CAZome, but
      were also enriched in genes associated with phospholipid metabolism, DNA
      synthesis and repair, iron homeostatis and autophagy. Two thirds of the CAZome
      was expressed both on wheat straw as well as on lactose, but 60% of it at least
      >2-fold higher on the former. Major wheat straw specific genes comprised
      xylanases, chitinases and mannosidases. Interestingly, the latter two CAZyme
      families were significantly higher expressed in a strain in which xyr1 encoding
      the major regulator of cellulase and hemicellulase biosynthesis is non
      functional. CONCLUSIONS: Our data reveal several major differences in the
      transcriptome between wheat straw and lactose which may be related to the higher
      enzyme formation on the former and their further investigation could lead to the
      development of methods for increasing enzyme production on lactose.

PMID- 24016405
TI  - A meta-analysis of neuropsychological markers of vulnerability to suicidal
      behavior in mood disorders.
AB  - BACKGROUND: Suicidal behavior results from a complex interplay between stressful
      events and vulnerability factors, including cognitive deficits. However, it is
      not clear which cognitive tests may best reveal this vulnerability. The objective
      was to identify neuropsychological tests of vulnerability to suicidal acts in
      patients with mood disorders. METHOD: A search was made of Medline, EMBASE and
      PsycINFO databases, and article references. A total of 25 studies (2323
      participants) met the selection criteria. A total of seven neuropsychological
      tests [Iowa gambling task (IGT), Stroop test, trail making test part B, Wisconsin
      card sorting test, category and semantic verbal fluencies, and continuous
      performance test] were used in at least three studies to be analysed. RESULTS:
      IGT and category verbal fluency performances were lower in suicide attempters
      than in patient controls [respectively, g = -0.47, 95% confidence interval (CI) 
      0.65 to -0.29 and g = -0.32, 95% CI -0.60 to -0.04] and healthy controls, with no
      difference between the last two groups. Stroop performance was lower in suicide
      attempters than in patient controls (g = 0.37, 95% CI 0.10-0.63) and healthy
      controls, with patient controls scoring lower than healthy controls. The four
      other tests were altered in both patient groups versus healthy controls but did
      not differ between patient groups. CONCLUSIONS: Deficits in decision-making,
      category verbal fluency and the Stroop interference test were associated with
      histories of suicidal behavior in patients with mood disorders. Altered value
      based and cognitive control processes may be important factors of suicidal
      vulnerability. These tests may also have the potential of guiding therapeutic
      interventions and becoming part of future systematic assessment of suicide risk.

PMID- 24016406
TI  - Status of treatment for the overall population of patients with stage IVb
      endometrial cancer, and evaluation of the role of preoperative chemotherapy: a
      retrospective multi-institutional study of 426 patients in Japan.
AB  - OBJECTIVE: We previously reported on the role of cytoreduction in 248 patients
      with surgical stage IVb endometrial cancer (EMCA). This study aimed to evaluate
      the clinical characteristics, prognosis according to initial treatment, and
      impact of preoperative chemotherapy in the overall population of patients with
      clinical and surgical stage IVb EMCA. METHODS: A multi-institutional
      retrospective analysis was performed in 426 patients diagnosed with clinical and
      surgical stage IVb EMCA from 1996 to 2005. Factors associated with overall
      survival (OS) were identified using univariate and multivariate analyses.
      RESULTS: The median OS for all 426 patients was 14 months. Patients were divided
      into three groups according to their initial treatment: primary surgery group
      (n=279), primary chemotherapy group (n=125), and palliative care group (n=22).
      The median OS times for these groups were 21, 12, and 1 month, respectively
      (p<0.0001). Patients in the primary surgery group had better performance status
      (PS) and lower numbers of extra-abdominal metastases than those in the primary
      chemotherapy group. Multivariate analysis identified good PS, endometrioid
      histology, absence of clinical intra-abdominal stage IVb metastasis,
      hysterectomy, and chemotherapy as independent predictors of OS. In the primary
      chemotherapy group, 59 patients subsequently underwent surgery, and these
      patients had similar OS to those in the primary surgery group. CONCLUSIONS:
      Hysterectomy and chemotherapy may prolong OS in selected patients with stage IVb
      EMCA. Our data suggest that primary chemotherapy followed by surgery may be a
      useful treatment choice in patients not suitable for primary surgery.

PMID- 24016407
TI  - Racial disparities and patterns of ovarian cancer surgical care in California.
AB  - OBJECTIVE: To investigate disparities in the frequency of ovarian cancer-related
      surgical procedures and access to high-volume surgical providers among women
      undergoing initial surgery for ovarian cancer according to race. METHODS: The
      California Office of Statewide Health Planning and Development database was
      accessed for women undergoing a surgical procedure that included oophorectomy for
      a malignant ovarian neoplasm between 1/1/06 and 12/31/10. Multivariate logistic
      regression analyses were used to evaluate differences in the odds of selected
      surgical procedures and access to high-volume centers (hospitals >= 20
      cases/year) according to racial classification. RESULTS: A total of 7933 patients
      were identified: White = 5095 (64.2%), Black = 290 (3.7%), Hispanic/Latino = 1400
      (17.7%), Asian/Pacific Islander = 836 (10.5%) and other = 312 (3.9%). White
      patients served as reference for all comparisons. All minority groups were
      significantly younger (Black mean age 57.7 years, Hispanic 53.2 years, Asian 54.5
      years vs. 61.1 years, p < 0.01). Hispanic patients had lower odds of obtaining
      care at a high-volume center (adjusted OR (adj. OR) = 0.72, 95% CI = 0.64-0.82, p
      < 0.01) and a lower likelihood of lymphadenectomy (adj. OR = 0.80, 95% CI=0.70
      0.91, p<0.01), bowel resection (adj. OR = 0.80, 95% CI = 0.71-0.91, p < 0.01),
      and peritoneal biopsy/omentectomy (adj. OR = 0.69, 95% CI = 0.58-0.82, p<0.01).
      Black racial classification was associated with a lower likelihood of
      lymphadenectomy (adj. OR = 0.76, 95% CI = 0.59-0.97, p = 0.03). CONCLUSIONS:
      Among women undergoing initial surgery for ovarian cancer, Hispanic patients are
      significantly less likely to be operated on at a high-volume center, and both
      Black and Hispanic patients are significantly less likely to undergo important
      ovarian cancer-specific surgical procedures compared to White patients.

PMID- 24016408
TI  - Does adjuvant chemotherapy improve survival for women with early-stage uterine
      leiomyosarcoma?
AB  - OBJECTIVES: To examine whether adjuvant therapy after primary surgery for
      treatment of early-stage uterine leiomyosarcoma (LMS) improves recurrence and
      survival rates. METHODS: A multisite, retrospective study of women diagnosed with
      stage I-II high grade LMS from 1990-2010 was performed. All patients (pts)
      underwent primary surgery followed by observation (OBS), radiotherapy (RT), or
      chemotherapy (CT) postoperatively. RESULTS: One hundred eight patients were
      identified with long-term follow-up; 94 pts (87.0%) had stage I and 14 (13.0%)
      had stage II disease. The mean patient age was 55.4 years and mean BMI was 28.0.
      Thirty-four (31.5%) patients underwent OBS, 35 (32.4%) received RT, and 39
      (36.1%) received chemotherapy. After a median follow-up of 41.8 months, a
      recurrence was diagnosed in 70.8%. Recurrence was evident in 25/34 (73.5%) OBS,
      23/35 (65.7%) RT, and 28/39 (71.8%) of CT cohorts and was not different based on
      treatment (p=0.413). However, extra-pelvic recurrences were significantly higher
      in the RT (95.2%) than in the OBS (60%) or CT (64.3%) cohorts (p=0.012).
      Additionally, recurrences were more likely to be successfully treated or
      palliated in those who initially received CT (p=0.031). On multivariate analysis,
      stage (p<0.001) and chemotherapy (p=0.045) were associated with overall survival.
      CONCLUSIONS: Women with early-stage, high grade uterine LMS experience high
      recurrence rates and poor survival outcomes, irrespective of adjuvant therapy.
      These rates are higher than previously reported in the literature. Although women
      treated with CT had similar recurrence rates as those treated with OBS or RT,
      treatment with adjuvant chemotherapy may decrease the risk of extra-pelvic
      recurrence and improve survival.

PMID- 24016409
TI  - Effect of surgical staging on 539 patients with borderline ovarian tumors: a
      Turkish Gynecologic Oncology Group study.
AB  - OBJECTIVE: The objectives of this study were to examine demographic and
      clinicopathologic characteristics and to determine the effects of primary
      surgery, surgical staging and the extensiveness of staging. METHODS: In a
      retrospective Turkish multicenter study, 539 patients, from 14 institutions, with
      borderline ovarian tumors were investigated. Some of the demographic, clinical
      and surgical characteristics of the cases were evaluated. The effects of type of
      surgery, surgical staging; complete or incomplete staging on survival rates were
      calculated by using Kaplan-Meier method. RESULTS: The median age at diagnosis was
      40 years (range 15-84) and 71.1% of patients were premenopausal. The most common
      histologic types were serous and mucinous. Majority of the staged cases were in
      Stage IA (73.5%). 242 patients underwent conservative surgery. Recurrence rates
      were significantly higher in conservative surgery group (8.3% vs. 3%). Of all
      patients in this study, 294 (54.5%) have undergone surgical staging procedures.
      Of the patients who underwent surgical staging, 228 (77.6%) had comprehensive
      staging including lymphadenectomy. Appendectomy was performed on 204 (37.8%) of
      the patients. The median follow-up time was 36 months (range 1-120 months). Five
      year survival rate was 100% and median survival time was 120 months. Surgical
      staging, lymph node sampling or dissection and appendectomy didn't cause any
      difference on survival. CONCLUSION: Comprehensive surgical staging, lymph node
      sampling or dissection and appendectomy are not beneficial in borderline ovarian
      tumors surgical management.

PMID- 24016410
TI  - Intraoperative hypothermia during primary surgical cytoreduction for advanced
      ovarian cancer: risk factors and associations with postoperative morbidity.
AB  - OBJECTIVE: The objective of this study was to evaluate the risk factors and
      potential morbidity associated with intraoperative hypothermia (IH) during
      cytoreductive surgery (CRS) for advanced ovarian cancer. METHODS: Demographic and
      perioperative data were collected for all patients with stage IIIC-IV ovarian,
      fallopian tube, and primary peritoneal carcinoma who underwent primary CRS at our
      institution from 2001 to 2010. Only patients with carcinomatosis and/or bulky
      upper abdominal disease and residual disease of <1cm were included.
      Intraoperative hypothermia was defined as temperature of <36.0 degrees Celsius (
      degrees C). Associations with 21 perioperative factors, 12 systems-based
      complications, and specific complications including but not limited to venous
      thromboembolism and surgical site infection were evaluated. RESULTS: Two hundred
      ninety-seven patients met the inclusion criteria. An intraoperative temperature
      <36 degrees C was noted in 72.1% of patients, and a temperature <36 degrees C at
      the time of abdominal closure was noted in 45.5%. Intraoperative vasopressors
      (P=0.02), epidural anesthesia (P=0.01), transfusion of fresh frozen plasma
      (P<0.05), and blood loss (P=0.01) were associated with IH. There was no
      association between IH and postoperative complications in general (P=0.48) or
      specifically grade 3-5 complications (P=0.34). Univariate analysis did show an
      association between hematologic complications and IH; however, this did not
      persist on multivariate analysis (P=0.14). CONCLUSIONS: In patients who underwent
      optimal primary CRS for advanced ovarian cancer, IH alone was not associated with
      the development of postoperative complications. Postoperative morbidity in these
      patients is multifactorial and further investigation into modifiable risk factors
      is warranted.

PMID- 24016411
TI  - Histochemistry and ultrastructure of urocytes in the pupae of the stingless bee
      Melipona quadrifasciata (Hymenoptera: Meliponini).
AB  - The main cell types of the adult bee fat body are trophocytes and oenocytes;
      however, in pupae of some newly emerged bees, trophocytes are modified into cells
      called urocytes, which possibly function as a substitute for Malpighian tubules
      during metamorphosis when larval tubules are not functional and/or storage of
      urate salts is required. This study evaluated the morphology of urocytes in the
      stingless bee Melipona quadrifasciata and the possibility of maintaining these
      cells in primary culture. The urocytes M. quadrifasciata are white spherical
      cells with an irregular surface as observed by stereomicroscopy. They may be
      found individually or in groups associated with tracheae. Urocytes have a single,
      small, and spherical nucleus and cytoplasm rich in neutral polysaccharides, lipid
      droplets, protein, and granules containing calcium and urate salts. Our findings
      suggest that urocytes play a role in storage of neutral polysaccharides and
      calcium in M. quadrifasciata pupae and that these cells can be cultured for 72 h.

PMID- 24016412
TI  - The role of gamma-secretase in hippocampal synaptic transmission and activity
      dependent synaptic plasticity.
AB  - gamma-Secretase plays an important role in the generation of amyloid beta and the
      activation of Notch receptors. In the hope that the reduction of amyloid
      production can help to battle Alzheimer's disease (AD) secretases were suggested
      to represent a potential therapeutic targets. However, the role of gamma
      secretase in cellular mechanisms of memory formation under physiological
      conditions remained to be clarified. To this end, gamma-secretase was inhibited
      by bath-application of DAPT or Compound E and the effects on activity-dependent
      hippocampal synaptic plasticity and basal synaptic transmission in acute
      hippocampal slices from Wistar rats were examined. Bath application of DAPT or
      Compound E over the whole recording period of field excitatory postsynaptic
      potential (fEPSP) caused a reduction of synaptic potentiation within 1h after
      3*1s 100Hz/10min stimulation (HFS) of Schaffer-collateral CA1 synapses. Notably,
      DAPT and Compound E inhibited effectively long-term potentiation (LTP) of fEPSPs
      when it was applied after HFS, but not if applied only during the tetanization
      paradigm. Compounds did not affect basal synaptic transmission, paired-pulse
      facilitation and NMDA mediated fEPSPs. Our data thus imply that gamma-secretase
      plays a role in LTP and most notably for the persistence of activity dependent
      synaptic plasticity, presumably through the reduction of endogenous amyloid beta
      and/or Notch receptor activation. Targeting of gamma-secretase to prevent the
      onset of AD might by itself alter memory formation. 

PMID- 24016413
TI  - Mannitol enhances therapeutic effects of intra-arterial transplantation of
      mesenchymal stem cells into the brain after traumatic brain injury.
AB  - Traumatic brain injury (TBI) sustained in a traffic accident or a fall is a major
      cause of death that affects a broad range of ages. The aim of this study was to
      investigate the therapeutic effects of intra-arterial transplantation of
      mesenchymal stem cells (MSCs) combined with hypertonic glycerol (25%) or mannitol
      (25%) in a TBI model of rats. TBI models were produced with a fluid percussion
      device. At 24h after TBI, MSCs (1*10(6)cells/100MUl) with glycerol or mannitol
      were administered via the right internal carotid artery. Rats were evaluated
      behaviorally and immunohistochemically, and hyperpermeability of the blood-brain
      barrier (BBB) induced by hypertonic solutions was explored. Compared to PBS or
      glycerol, the administration of mannitol resulted in increased BBB disruption.
      The mannitol-treated rats showed significant improvement in motor function. Intra
      arterial transplantation of MSCs caused no thromboembolic ischemia.
      Immunohistochemically, more MSCs were observed in the injured brain tissues of
      mannitol-treated rats than in glycerol or PBS-treated rats at 24h after
      transplantation. Intra-arterial transplantation of MSCs combined with mannitol is
      an effective treatment in a TBI model of rats. This technique might be used for
      patients with diseases of the central nervous system including TBI. 

PMID- 24016414
TI  - Treatment with phenylbutyrate in a pre-clinical trial reduces diarrhea due to
      enteropathogenic Escherichia coli: link to cathelicidin induction.
AB  - Treatment of shigellosis in rabbits with phenylbutyrate reduces clinical severity
      and counteracts down-regulation of cathelicidin (CAP-18) in the large intestinal
      epithelia. We aimed to further evaluate whether in a rabbit model of
      enteropathogenic Escherichia coli (EPEC) diarrhea, CAP-18 is down-regulated in
      the small intestine and if oral phenylbutyrate treatment affects CAP-18
      expression, clinical recovery, shedding of EPEC in stool and virulence properties
      of the isolated colonies. EPEC-induced diarrhea down-regulated CAP-18 in the
      small intestinal epithelia as revealed by immunohistochemistry. Phenylbutyrate
      treatment reduced clinical illness, improved histological features of
      inflammation and up-regulated CAP-18 in the epithelia. Active CAP-18 peptide was
      also released in the stool as noted in Western blot analysis. Multiplex PCR
      analysis of total bacterial DNA in the stool showed absence of EPEC specific
      genes eae and bfpA. Treated rabbits shed rough strains still harboring eae and
      bfpA genes, which were less potent in binding to HeLa cells and induced delayed
      onset of diarrhea in new rabbits. In conclusion, EPEC-mediated down-regulation of
      CAP-18 in the small intestinal epithelia was restored by phenylbutyrate
      treatment. Upregulation of CAP-18 in the epithelia was accompanied by healing of
      the epithelial lining, reduced shedding and virulence of EPEC and recovery from
      diarrhea. 

PMID- 24016416
TI  - The effect of a cognitive task on the postural control of dyslexic children.
AB  - We explore the influence of a secondary cognitive task on concurrent postural
      control in dyslexic children. Seventeen children with dyslexia (DYS) were
      compared with thirteen non-dyslexic children (NDYS). Postural control was
      recorded in Standard Romberg (SR) and Tandem Romberg (TR) conditions while
      children, in separate sessions, have to fixate on a target and name simple
      objects appearing consecutively on a computer screen. The surface, the length and
      the mean speed of the center of pressure were analyzed; the percentage of correct
      responses to the cognitive task was also measured. DYS are significantly more
      unstable than NDYS. The secondary cognitive task significantly decreases the
      postural stability in DYS only. For both children postural performances in the TR
      condition is significantly worse than in the SR condition. The percentage of
      wrong responses to the cognitive task is significantly higher in DYS. Postural
      instability observed in DYS supports the hypothesis that there is a deficit of
      automatic integration of visual information and postural control in these
      children. This result is in line with the U-shaped non linear model showing that
      a secondary task performed during a postural task leads to an impaired postural
      stability probably due to focus attention on the cognitive task. 

PMID- 24016415
TI  - Association of a risk allele of ANK3 with cognitive performance and cortical
      thickness in patients with first-episode psychosis.
AB  - BACKGROUND: The gene ANK3 is implicated in bipolar disorder and schizophrenia.
      The present study investigated the influence of this gene on cognitive
      performance and brain structure among individuals with first-episode psychosis
      (FEP). The brief illness duration of an FEP sample makes it well suited for
      studying the effects of genetic variation. METHODS: We genotyped 2 single
      nucleotide polymorphisms (SNPs; rs1938526 and rs10994336) in ANK3 in patients
      with FEP. Multivariate analysis of variance compared risk allele carriers and
      noncarriers on 6 domains of cognition consistent with MATRICS consensus. A
      subsample of 82 patients was assessed using magnetic resonance imaging. We
      compared brain structure between carriers and noncarriers using cortical
      thickness analysis and voxel-based morphometry on white matter. RESULTS: In the
      173 patients with FEP included in our study, rs1938526 and rs10994336 were in
      very high linkage disequilibrium (d' = 0.95), and analyses were therefore only
      carried out on the SNP (rs1938526) with the highest minor allele frequency (G).
      Allele G of rs1938526, was associated with lower cognitive performance across
      domains (F6,164 = 2.38, p = 0.030) and significantly lower scores on the domains
      of verbal memory (p = 0.015), working memory (p = 0.006) and attention (p =
      0.019). The significant effects of this SNP on cognition were not maintained when
      controlling for IQ. Cortical thinning was observed in risk allele carriers at
      diverse sites across cortical lobes bilaterally at a threshold of p < 0.01, false
      discovery rate-corrected. Risk-allele carriers did not show any regions of
      reduced white matter volume. LIMITATIONS: The sample size is modest given that a
      low-frequency variant was being examined. CONCLUSION: The ANK3 risk allele
      rs1938526 appears to be associated with general cognitive impairment and
      widespread cortical thinning in patients with FEP.

PMID- 24016417
TI  - Discrepancies between mothers and clinicians in assessing functional capabilities
      and performance of children with cerebral palsy.
AB  - The current study is a cross-sectional study that aimed to investigate the
      concordance between health care professionals (HCPs) and mothers in rating
      capabilities and performance of children with cerebral palsy (CP), and the impact
      of CP gross motor severity on concordance. Seventy-three children with mild-to
      severe CP (mean age 8.8 +/- 2.10 years) and their mothers participated in this
      study. Two modes of Pediatric Evaluation Disability Inventory (PEDI)
      administration were used: mothers' interview by a social worker and HCPs' actual
      evaluation. Differences between raters were assessed by paired t-tests and intra
      class correlation coefficients (ICCs). Agreement was defined as mean absolute
      difference of less than or equal to six points. The results indicated that in
      spite of excellent overall ICCs in PEDI (ICC>0.8), disagreement between raters
      was observed in all PEDI sub-domains: 38%, 56%, 72% and 59% disagreement in
      Functional Skills-Mobility, Functional Skills-Self Care, Caregiver Assistance
      Mobility (CA-MO) and Caregiver Assistance-Self Care (CA-SC), respectively. In CA
      SC and CA-MO disagreement mainly consisted of mothers rating their children lower
      in performance than HCPs. CP severity effected the agreement mostly in children
      with moderate CP severity. The implications of these results are that raters
      perceive child's activity differently, hence revealing hidden disability
      perceptions, with significant consequences for intended interventions.

PMID- 24016418
TI  - Programmed sickle cells for targeted delivery to hypoxic tumors.

PMID- 24016419
TI  - Airbrushed nickel nanoparticles for large-area growth of vertically aligned
      carbon nanofibers on metal (Al, Cu, Ti) surfaces.
AB  - Vertically aligned carbon nanofibers (VACNFs) were grown by plasma-enhanced
      chemical vapor deposition (PECVD) using Ni nanoparticle (NP) catalysts that were
      deposited by airbrushing onto Si, Al, Cu, and Ti substrates. Airbrushing is a
      simple method for depositing catalyst NPs over large areas that is compatible
      with roll-to-roll processing. The distribution and morphology of VACNFs are
      affected by the airbrushing parameters and the composition of the metal foil.
      Highly concentrated Ni NPs in heptane give more uniform distributions than
      pentane and hexanes, resulting in more uniform coverage of VACNFs. For VACNF
      growth on metal foils, Si micropowder was added as a precursor for Si-enriched
      coatings formed in situ on the VACNFs that impart mechanical rigidity.
      Interactions between the catalyst NPs and the metal substrates impart control
      over the VACNF morphology. Growth of carbon nanostructures on Cu is particularly
      noteworthy because the miscibility of Ni with Cu poses challenges for VACNF
      growth, and carbon nanostructures anchored to Cu substrates are desired as anode
      materials for Li-ion batteries and for thermal interface materials. 

PMID- 24016420
TI  - Tyrosinemia type 1: a rare and forgotten cause of reversible hypertrophic
      cardiomyopathy in infancy.
AB  - BACKGROUND: Tyrosinemia type 1 (TT1) is an autosomal recessive disorder caused by
      deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). TT1 usually
      presents in infancy with features suggestive of liver disease or with sepsis-like
      symptoms. CASE PRESENTATION: We report two Saudi siblings with TT1. Case 1 was a
      male infant who presented at 2 months old with fever, vomiting and refusal of
      feeding. Examination revealed a sick-looking infant with signs of severe
      dehydration and hypovolemic shock. He was jaundiced, and had hepatomegaly and
      elevated liver enzymes. Echocardiography was performed in light of a lack of
      response to inotropes, and revealed biventricular and interventricular septal
      hypertrophies. The ventricular ejection fraction was 65%. Urine organic acid
      analysis showed elevated succinylacetone, consistent with a diagnosis of TT1. An
      FAH gene study identified a c.1 A > G homozygous mutation. This patient responded
      well to intensive cardiorespiratory therapy, tyrosine-free formula, and oral 2
      nitro-4- trifluoromethylbenzyl 1, 3 cyclohexanedione (NTBC). Echocardiographic
      findings reverted to normal after 4 weeks. Case 2 was the younger brother of Case
      1, and was born 6 months after his brother had been confirmed with tyrosinemia.
      Pregnancy and delivery were uneventful. Serum amino acid and organic acid
      analyses 4 days after birth confirmed tyrosinemia. DNA analysis identified a c.1
      A > G homozygous mutation, as in his brother. Echocardiography was normal.
      Special formula and NTBC were commenced on day 7 of life. The infant remained
      asymptomatic after 9 months of follow-up. CONCLUSIONS: These cases highlight TT1
      as a treatable cause of cardiomyopathy in children. It also supports the idea
      that early diagnosis and treatment may prevent the development of cardiomyopathy
      associated with tyrosinemia.

PMID- 24016421
TI  - Single-molecule views on homologous recombination.
AB  - All organisms need homologous recombination (HR) to repair DNA double-strand
      breaks. Defects in recombination are linked to genetic instability and to
      elevated risks in developing cancers. The central catalyst of HR is a
      nucleoprotein filament, consisting of recombinase proteins (human RAD51 or
      bacterial RecA) bound around single-stranded DNA. Over the last two decades,
      single-molecule techniques have provided substantial new insights into the
      dynamics of homologous recombination. Here, we survey important recent
      developments in this field of research and provide an outlook on future
      developments. 

PMID- 24016422
TI  - Effect of heat stress and feeding phosphorus levels on pig electron transport
      chain gene expression.
AB  - The purpose of this study was to evaluate the effect of temperature and different
      levels of available phosphorus (aP) on the expression of nine genes encoding
      electron transport chain proteins in the Longissimus dorsi (LD) muscle of pigs.
      Two trials were carried out using 48 high-lean growth pigs from two different
      growth phases: from 15 to 30 kg (phase 1) and from 30 to 60 kg (phase 2). Pigs
      from growth phase 1 were fed with three different levels of dietary aP (0.107%,
      0.321% or 0.535%) and submitted either to a thermoneutral (24 degrees C and RH at
      76%) or to a heat stress (34 degrees C and RH at 70%) environment. Pigs from
      growth phase 2 were fed with three different levels of dietary aP (0.116%, 0.306%
      or 0.496%) and submitted either to a thermoneutral (22oC and RH at 77%) or to a
      heat stress (32oC and RH at 73%) environment. Heat stress decreased (P<0.001)
      average daily feed intake at both growth phases. At 24 degrees C, pigs in phase 1
      fed the 0.321% aP diet had greater average daily gain and feed conversion
      (P<0.05) than those fed the 0.107% or 0.535% while, at 34 degrees C pigs fed the
      0.535% aP had the best performance (P<0.05). Pigs from phase 2 fed the 0.306% aP
      had best performance in both thermal environments. Gene expression profile was
      analyzed by quantitative real-time polymerase chain reaction. Irrespective of
      growing phase, the expression of six genes was lower (P<0.05) at high temperature
      than at thermoneutrality. The lower expression of these genes under high
      temperatures evidences the effects of heat stress by decreasing oxidative
      metabolism, through adaptive physiological mechanisms in order to reduce heat
      production. In pigs from phase 1, six genes were differentially expressed across
      aP levels (P<0.05) in the thermoneutral and one gene in the heat stress. In pigs
      from phase 2, two genes were differentially expressed across aP levels (P<0.05)
      in both thermal environments. These data revealed strong evidence that phosphorus
      and thermal environments are key factors to regulate oxidative phosphorylation
      with direct implications on animal performance. 

PMID- 24016423
TI  - Biomimetic superhydrophobic surface of high adhesion fabricated with micronano
      binary structure on aluminum alloy.
AB  - Triggered by the microstructure characteristics of the surfaces of typical plant
      leaves such as the petals of red roses, a biomimetic superhydrophobic surface
      with high adhesion is successfully fabricated on aluminum alloy. The essential
      procedure is that samples were processed by a laser, then immersed and etched in
      nitric acid and copper nitrate, and finally modified by DTS
      (CH3(CH2)11Si(OCH3)3). The obtained surfaces exhibit a binary structure
      consisting of microscale crater-like pits and nanoscale reticula. The
      superhydrophobicity can be simultaneously affected by the micronano binary
      structure and chemical composition of the surface. The contact angle of the
      superhydrophobic surface reaches up to 158.8 +/- 2 degrees . Especially, the
      surface with micronano binary structure is revealed to be an excellent adhesive
      property with petal-effect. Moreover, the superhydrophobic surfaces show
      excellent stability in aqueous solution with a large pH range and after being
      exposed long-term in air. In this way, the multifunctional biomimetic structural
      surface of the aluminum alloy is fabricated. Furthermore, the preparation
      technology in this article provides a new route for other metal materials. 

PMID- 24016424
TI  - Processing of S-cone signals in the inner plexiform layer of the mammalian
      retina.
AB  - Color information is encoded by two parallel pathways in the mammalian retina.
      One pathway compares signals from long- and middle-wavelength sensitive cones and
      generates red-green opponency. The other compares signals from short- and middle
      /long-wavelength sensitive cones and generates blue-green (yellow) opponency.
      Whereas both pathways operate in trichromatic primates (including humans), the
      fundamental, phylogenetically ancient color mechanism shared among most mammals
      is blue-green opponency. In this review, we summarize the current understanding
      of how signals from short-wavelength sensitive cones are processed in the primate
      and nonprimate mammalian retina, with a focus on the inner plexiform layer where
      bipolar, amacrine, and ganglion cell processes interact to facilitate the
      generation of blue-green opponency. 

PMID- 24016425
TI  - [Behavioral and ecological infectious diseases: from SARS to H7N9 avian influenza
      outbreak in China].

PMID- 24016426
TI  - [Epidemiologic and genetic characteristics of hepatitis E virus in Shanghai, 1997
      2012].
AB  - OBJECTIVE: The aim of this study was to systemically analyze the epidemiologic,
      serological and genetic characteristics of hepatitis E virus (HEV) in Shanghai
      from 1997 to 2012. METHODS: We analyzed the data related to the epidemics of
      hepatitis E from China Information System for Disease Control and Prevention. We
      implemented serological surveillance program, based on community healthy
      population with enzyme-linked immunosorbent assay method and estimated the
      standardized sero-prevalence. We also obtained nucleotide sequences of hepatitis
      E patients using the nested RT-PCT assays, together with prototype sequences in
      the GenBank to construct a HEV genetic database in Shanghai. RESULTS: In this
      paper, we found that the distribution of hepatitis E patients was sporadic in the
      past 16 years in Shanghai. The morbidity kept declining, but with seasonal and
      periodical fluctuation. Morbidity in males was significantly higher than in
      females, with the hard hit population between 30 and 65 year-olds. In total, 3979
      sera samples were collected through the serological surveillance programs in
      2001, 2004, 2007 and 2012. The standardized sero-prevalence rates of the said
      years were 22.32%, 18.56%, 10.22% and 34.43% which all showing strong
      relationship with age groups and the regions where the populations were being
      monitored. 73 nucleotide sequences of hepatitis E patients from hospitals were
      identified, during 2004 and 2008. RESULTS: from phylogenetic analysis revealed
      that all HEV isolates belonged to genotype IV and including 4 known subtypes 4a,
      4d, 4h and 4i which sharing 83.09% - 97.96%, 85.87% - 97.26% and 83.80% - 95.10%
      nucleotide sequence identities with the swine HEV genotype IV of GU188851,
      DQ450072 and EF570133. Meanwhile, 59 HEV isolates from different districts shared
      99% nucleotide sequence identities with each other. CONCLUSION: Hepatitis E would
      still be a challenge for long time and the zoonotic questions that related to
      hepatitis E, need to be explored and explained in the future.

PMID- 24016427
TI  - [Genotyping of Mycobacterium leprae in Guangdong province].
AB  - OBJECTIVE: To understand the genotypes of Mycobacterium leprae collected from
      Guangdong province, China and to analyze the routes of leprosy transmission both
      inside and outside of Guangdong. The impact of emigrant leprosy patients to the
      endemic nature of the disease in Guangdong was also studied. METHODS: Typing on
      strains with variable number of tandem repeats (VNTR) and single nucleotide
      polymorphism (SNP) were performed on the local cases and emigrant cases based on
      skin biopsy. RESULTS: Most isolates from local patients belong to SNP type 1 and
      SNP type 3 isolates were found just in a small part of local isolates. However,
      all the emigrants were carrying SNP type 3. Within the SNP type 1 strain from
      Guangdong, alleles at the 18-8, 12-5, ML-1, (TA) 10 and (GGT) 5 differed from SNP
      3 strains collected from other areas in China. However, all the SNP type 1 and
      SNP type 3 local isolates identified from Guangdong were having close VNTR
      profiles and the main differences appeared in the alleles at ML-1, (TA) 10 and
      (GGT) 5. CONCLUSION: The transmission of strain with SNP type 1 seemed to be
      associated to the "Silk Road on the Sea", calling for monitoring and confirming
      the transmission of patients with SNP type 3 in Guangdong were from the secondary
      transmission, by the emigrant patients. Further study on the historic spread and
      phylogenetic relationships between SNP type 1 and novel SNP type 3 in Guangdong
      is needed.

PMID- 24016428
TI  - [An outbreak of imported dengue fever from Myanmar to the border of China, with
      its viral molecular epidemiological features].
AB  - OBJECTIVE: To understand the epidemiologic characteristics of dengue fever,
      imported from Myanmar to the border of Yunnan province, China. Viral molecular
      epidemiologic features were also studied. METHODS: Questionnaires were used on
      each diagnosed, suspected dengue fever, case or unknown cases with fever when
      coming from Myanmar entering the port and hospitals in Ruili city of Yunnan
      province. Serum samples of these patients were collected to detect IgM antibody
      against dengue virus and RT-PCR assay. Homology and phylogenetic tree based on
      the whole nucleotide sequence of PrM-C and NS5 gene of dengue virus were further
      analyzed. RESULTS: A total of 103 sera were collected from patients at acute
      stage in Ruili city in July to November 2008. Among them, 49 cases were confirmed
      for dengue fever according to IgM and nucleic acid testings. Except one, other 48
      cases were all imported into Ruili, from Myanmar. Of those, 18 patients were
      residents from Mujie city of Myanmar and hospitalized in Ruili and the rest 30
      patients were Chinese citizens who had finished business and returned from
      Myanmar. Two isolates of serum samples from the imported cases were identified
      and both homology and phylogenetic analysis were performed, using the nucleotide
      sequences of PrM and NS5 genes. They were divided into dengue type 1 (RLB61) and
      dengue type 3 (RLC31) and were closer to the dengue virus strains isolated from
      Southeast Asia countries. CONCLUSION: It is confirmed that an epidemic of dengue
      fever which was imported from Myanmar to Ruili city of Yunnan province, China.
      Evidence also showed that both type I and III epidemic strains of dengue virus
      did exist in Mujie city of Myanmar in 2008.

PMID- 24016429
TI  - [Analysis on genotype distributions and epidemiological characteristics of
      Yersinia pestis plague foci in Gansu province].
AB  - OBJECTIVE: To study the genotype distributions and epidemiological
      characteristics of Yersinia pestis in Gansu province. METHODS: Primers were
      designed according to the confirmed 23 differential sections, to genotype the 202
      Yersinia pestis DNA of Gansu province by PCR, and to analyze its distribution and
      epidemiological characteristics. RESULTS: Yersinia pestis in Gansu province could
      be divided into eight genotypes: 1b, 5, 7, 8, 13, 26, new genotype 1 (GS1) and
      new genotype 2 (GS2). They were distributed in various regions. 1b, 8 and GS1
      genotypes of Yersinia pestis had been identified since 1960s but the 7, 13 and 26
      genotypes had not been isolated for more than 40 years while GS2 and 5 genotypes
      had been isolated since 1990s. CONCLUSION: 1b, 8 and GS1 genotypes of Yersinia
      pestis continued to be violently prevalent since 1960s but 7, 13 and 26 genotypes
      had not been isolated for more than 40 years while GS2 and 5 genotypes had
      started to be popular since 1990s.

PMID- 24016430
TI  - [Investigation on the endemic foci of new emerged tick-borne encephalitis in
      Charles Hilary, Xinjiang].
AB  - OBJECTIVE: To investigate the recent emerged endemic region of tick-borne
      encephalitis (TBE) regarding its natural reserves, in Charles Hilary, northern
      Xinjiang and to isolate and characterize the viral geographic strain. METHODS:
      Using indirect fluorescent assay to detect tick-borne encephalitis virus (TBEV)
      specific IgG antibodies from serum of local residents including 2 unconfirmed
      viral encephalitis patients in 2011 spring-summer. Viruses were isolated from
      tick samples by inoculating BALB/c mice and BHK-21 cells. For phylogenetic
      analysis. TBEV NS1 gene fragments were detected by RT-PCR and then subjected to
      sequence alignment. RESULTS: 1760 ticks were captured from the fields to have
      found that Ixodes persulcatus were dominated among the tick population. Two viral
      encephalitis patients were diagnosed as TBEV infection. In addition, 35.4%
      (23/65) local residents were detected positive for presence of TBEV specific-IgG
      antibodies in serum. After inoculation, morbidity and mortality of BALB/c mice
      were 72.9% (70/96) and 55.7% (44/79), respectively. TBEV specific-fragments were
      amplified from brain tissue of dead mice and cells culture supernatant. NS1
      sequence alignment showed that the viral isolates were clustered into TBEV far
      eastern sub-type, phylogenetically, and were mostly close to the isolates from
      northeastern China (99%) and Russian strain (98%). CONCLUSION: In this study, a
      new endemic loci of TBE was firstly described in Charles Hilary natural reserve,
      northern Xinjiang. TBEV geographic isolates belonged to TBEV far-eastern subtype
      while Ixodes persulcatus and Dermacentor silvarum played crucial roles for
      disease transition.

PMID- 24016431
TI  - [Clinical and epidemiological characteristics of the 6 confirmed human cases with
      novel influenza A (H7N9) virus infection in Zhejiang].
AB  - OBJECTIVE: To explore the clinical spectrum, geographic location of human H7N9
      avian influenza as well as the characteristics of population at high risk of
      infection, in order to develop strategies for the prevention and control of the
      infection. Clinical and epidemiological characteristics on the 6 confirmed human
      cases in Zhejiang were also analyzed. METHODS: Real-time fluorescent quantitative
      PCR was used to test the nucleic acid of human H7N9 avian influenza infection,
      from pharyngeal swabs of the patients and their close contacts. Face to face
      interview and descriptive method were used to collect related clinical and
      epidemiological data. Statistical analysis was performed by SPSS 17.0. RESULTS:
      Six confirmed cases were distributed in Hangzhou and Huzhou cities. The 6
      confirmed human cases, including 5 males and 1 female were all confirmed with
      novel influenza A (H7N9) virus infection, with an average age as 60.83 years
      (with median as 64.50 years). Cough was the most common initial symptom to be
      noticed. The clinical manifestations would include fever, dizziness, pain of
      muscles, coughing, expectoration and short of breath. All the X-ray chest films
      showed severe pneumonia, and 5 of them having had other chronic diseases. None of
      the cases admitted to have had a history of exposure to ill/death avians.
      However, all of the cases had been frequently exposed to the agricultural
      byproduct-trading-markets where the positive rate of novel influenza A (H7N9)
      virus in environmental specimens was up to 43.21%. 32 of the 375 close contacts
      (8.53%) to the 6 cases appeared abnormal symptoms, but no positive result related
      to novel influenza A (H7N9) virus nucleic acid was detected from their throat
      swabs. CONCLUSION: Acute infection on the respiratory system seemed the main
      clinical manifestation. Elderly men, especially those with chronic diseases were
      under high risk of human infection with H7N9 avian influenza. The source of
      infection might be associated with the exposure to poultry. There was still lack
      of evidence to confirm the route of person to person transmission on H7N9 avian
      influenza.

PMID- 24016432
TI  - [Prevalence of nonalcoholic fatty liver disease and metabolic abnormalities in
      387 obese children and adolescents in Beijing, China].
AB  - OBJECTIVE: To determine the prevalence of nonalcoholic fatty liver disease
      (NAFLD) and metabolic abnormalities in obese children and adolescents in Beijing.
      METHODS: This study involved 387 obese children and adolescents, aged 12 to 17
      years in Beijing. Data on anthropometric measurements was collected, including
      weight, height and age. All subjects underwent a clinic examination containing
      fasting blood and liver ultrasonography. Nonalcoholic fatty liver disease was
      diagnosed using diagnostic criteria for nonalcoholic fatty liver disease which
      was recommended by the Fatty liver and Alcoholic Liver Disease Study Group of
      Liver Disease Association in China. RESULTS: 174 out of the 387 children were
      diagnosed as having NAFLD. The overall prevalence of NAFLD was 45.0% in this
      study population. The prevalence rates of NAFLD did not show significant
      difference between girls and boys. The prevalence rates of diabetes mellitus and
      IFG were 0.8% and 49.1% respectively. The prevalence rates of HTG, HTC, HLDL-C,
      LHDL-C, IFG, elevated ALT (or AST) and acanthosis nigricans were 6.3%, 4.0%,
      37.9%, 22.8%, 46.0%, 17.8% and 28.5% in students combined with obesity and NAFLD,
      respectively. In the NAFLD subgroup, higher prevalence of high TG, acanthosis
      nigricans, abnormal ALT or AST were seen. With the increasing of obesity, the
      level of LDL-C, TG, liver function disturbance and prevalence of NAFLD and
      acanthosis nigricans were aggravated. Under binary logistic regression analysis,
      results showed that high BMI, acanthosis nigricans and TG were significantly
      correlated with NAFLD in obese children and adolescent population. CONCLUSION:
      NAFLD was common in obese children, and the prevalence of NAFLD in obese children
      was 45.0%. Higher BMI, acanthosis nigricans and abnormal TG were independent risk
      factors for NAFLD in obese children. Obese children who had been exposed to high
      risk factors should take the ultrasonography.

PMID- 24016433
TI  - [Epidemiological characteristics of major abnormal electrocardiogram in adults
      from Shanghai].
AB  - OBJECTIVE: To understand the prevalence, characteristics and risk factors of
      major abnormal electrocardiogram (MA-ECG) in adults living in Shanghai. METHODS:
      The cross-sectional dataset of prevalence survey on diabetes and metabolic
      syndrome in adults, aged 20-74 years, from Shanghai, in 2007-2008, was analyzed.
      Demographic information, personal and, family histories of diseases were
      collected. Physical examination and laboratory tests were done. Subjects
      underwent examination on resting 12-leads electrocardiogram (ECG), ECG records
      were coded according to the Minnesota criteria and classified as MA-ECG or non-MA
      ECG. RESULTS: A total number of 5364 subjects (2003 men, 3361 women) were finally
      included in this analysis. (1) The standardized prevalence of MA-ECG was 7.3%
      (7.0% in men, 7.7% in women). In both genders, the age-specific prevalence of MA
      ECG significantly increased with age (Ptrend < 0.01). The age-specific prevalence
      of MA-ECG in youths, middle aged and the elderly were 2.3%, 7.7%, and 17.3% in
      men, and 3.3%, 8.8% and 16.4% in women, respectively (both Ptrend < 0.01). (2)
      The three most common MA-ECG forms were arrhythmia (28.8%), bundle branch block
      (26.5%) and ST segment depression (20.0%) in men, while there appeared ST segment
      depression (44.6%), arrhythmia (23.0%) and combined MA-ECG (11.8%) in women. (3)
      Data from multivariate logistic regression analysis showed that other than age,
      coronary heart disease (CHD) was the only independent risk factor of MA-ECG in
      men, with its corresponding OR being 2.33 - 2.39; while in women, menopause (OR
      value: 1.72 - 1.85) and hypertension (OR value: 1.33 - 1.34) were main factors
      related to MA-ECG. CONCLUSION: MA-ECG was prevalent in the middle aged and the
      elderly, with, arrhythmia and ST segment depression the most frequent forms of MA
      ECG. Age, CHD and hypertension were the main risk factors of MA-ECG in the adults
      from Shanghai.

PMID- 24016434
TI  - [Association between serum calcium levels and the risk of liver cirrhosis].
AB  - OBJECTIVE: To examine the association between serum calcium levels and the risk
      of liver cirrhosis. METHODS: A nested case-control study was performed based on
      the nutritional intervention trial of esophageal carcinoma in Linxian, Henan
      province. Serum samples of 281 liver cirrhosis cases and 562 controls were tested
      for calcium concentrations, surface antigen (HBsAg) and core antibody (anti-HBc)
      on Hepatitis virus B and antibody on Hepatitis virus C (anti-HCV), using
      automatic serum biochemical analysis system and enzyme-linked immunoassay. Data
      on baseline characteristics were collected via a questionnaire. Serum calcium
      value was divided into tertiles and logistic regression model was used to
      calculate odds ratios and 95% confidence intervals. RESULTS: Individuals in the
      case group showed higher calcium levels (1.81 +/- 0.84) mmol/L when compared to
      the controls (1.65 +/- 0.79) mmol/L, with t = -2.640 and P = 0.008. The calcium
      levels were associated with the risk of liver cirrhosis (chi(2) = 6.888, P =
      0.0319). Risks for the individuals in the highest tertile were doubled when
      compared to the lowest (adjusted OR = 2.261, 95%CI: 1.497 - 3.416, P = 0.002). A
      positive correlation was observed between serum calcium level and the risk of
      liver cirrhosis (chi(2) = 6.842, P = 0.0089). CONCLUSION: from our study revealed
      that the elevated serum calcium level might be an independent risk factor for
      liver cirrhosis. However, further investigations are anticipated to explore its
      potential mechanisms.

PMID- 24016435
TI  - [Assessment on depressive status and the therapeutic effects of highly active
      antiretroviral therapy among anti-HIV-1(+) population].
AB  - OBJECTIVE: To assess the depressive status and its influence on Chinese HIV-1(+)
      population, and how it was influenced by highly active antiretroviral therapy
      (HAART) and the CD4(+) T cell count. METHODS: Anti-HIV-1(+) patients (age between
      18 and 65 years old) who had met the criteria to commence the anti-HIV treatment
      but had not yet started, were selected from the Beijing Ditan Hospital between
      March 2011 and June 2012. BDI-II (Beck Depression Inventory) and a self-designed
      questionnaire were used to evaluate the baseline and the status of 48 weeks post
      the HAART treatment. Statistically, t test and the Wilcoxon rank sum test were
      used to compare the BDI scores under different conditions and before/after the
      HAART. RESULTS: (1) Of 100 subjects: male to female ratio was 99:1; the average
      age was 31.37 +/- 5.58 years; the average education background was of 13.13 +/-
      3.51 years; the unemployed percentage was 4%; time before being identified as
      anti-HIV-1(+) was 5.0 (1.0 - 21.0) months; the percentage being infected through
      homosexual contact was 83%. The baseline BDI score was 6.0 (3 - 10.25). (2) There
      was no significant difference (P > 0.05) in BDI score between those subjects
      having had education less or more than 12 years; the BDI score of patients whose
      anti-HIV-1(+) was significantly higher (P < 0.05) among those discovered within
      the past 6 months than those more than 6 months. The BDI score of patients whose
      baseline CD4(+) T cell count below 200 cells/ul was significantly higher (P <
      0.05) than those with baseline CD4(+) T cell count greater than 200 cells/ul. The
      CD4(+) T cell count was significantly high (P < 0.001) after 48 weeks of anti
      viral treatment, but the BDI score was not significantly different (P > 0.05).
      There was no significant change (P > 0.05) in the proportion of patients with
      different degrees of BDI score before and after 48 weeks of antiviral treatment.
      CONCLUSION: Depression in HIV patients was most overt in the first six months
      when they were aware of the infection. The degree of depression was more severe
      in patients with baseline CD4(+) T cell count less than 200 cells/ul with
      improvement of immunity after the HAART did not alleviate the level of
      depression.

PMID- 24016436
TI  - [A cross-sectional study on iodine nutrition in general population from Zhejiang
      province, China].
AB  - OBJECTIVE: To understand the current status of iodine nutrition among the
      community residents to compare the level of iodine nutrition in different areas
      and groups of populations in Zhejiang province. METHODS: Stratified cluster
      sampling method was adopted and residents from twenty-two communities in Zhejiang
      province were selected. A cross-sectional survey was conducted, using
      questionnaires, laboratory tests, on urinary iodine, water iodine and the
      concentration of the iodine in salt, which had played positive roles in the
      calculation of the level of iodine nutrition. RESULTS RESULTS: of the iodine
      nutrition in this cross-sectional survey were as follows: the median water iodine
      and salt iodine of Zhejiang were 2.42 ug/L and 28.8 mg/kg, respectively. The
      coverage of iodized salts was 79.54%, with the ingesting rate of qualified
      iodized-salt as 76.65% and the median content of urinary iodine in the population
      of Zhejiang was 161 ug/L. The average iodine content among pregnant women was 138
      ug/L, with the percentage of samples less than 100 ug/L as 25.92%, more than 300
      ug/L as 15.30%. The proportions of iodine intake through water, salt and other
      foods were 1.70%, 76.41% and 21.89%, respectively. CONCLUSION: The status of
      iodine nutrition in Zhejiang province in general seemed to be appropriate, but
      the level of iodine nutrition in pregnant women was less than the requirement,
      which should call for attention.

PMID- 24016437
TI  - [Study on the relationship between college students' physical quality and the
      quality of sleep].
AB  - OBJECTIVE: The author wants to investigate the relationship between college
      students' physical quality and the quality of sleep. METHODS: Stratified cluster
      sampling method is used, and invites a total of 2981 Anhui college students to
      take part in the questionnaire study, the Pittsburgh sleep quality index (PSQI)
      and physical test, in order to survey the sleep quality and physical quality of
      college students. The physical quality and sleep quality are analyzed by the
      multiple factor non conditional logistic regression analysis methods. RESULTS:
      PSQI scores of the 2744 students are (5.378 +/- 2.492), 477 people (17.4%) have
      poor sleep quality. The endurance, speed, strength quality scores are (75.850 +/-
      13.279), (69.760 +/- 16.422), (66.278 +/- 18.709) points. Logistic regression
      analysis shows that excellent endurance (OR = 0.418) is a protective factor of
      sleep quality. CONCLUSION: The improvement of endurance may improve sleep
      quality.

PMID- 24016438
TI  - [A prevalence study on mild cognitive impairment among elderly populations in
      Zhejiang province].
AB  - OBJECTIVE: To understand the prevalence of older people with mild cognitive
      impairment (MCI) in Zhejiang province and to provide the basis for elderly early
      detection and diagnosis of Alzheimer's disease (AD). METHODS: 1211 more than 60
      year-old elderly populations were selected in Zhejiang province, and were given
      screening questionnaire by general information, the montreal cognitive assessment
      (MoCA) and mini-mental state examination (MMSE). RESULTS: MCI prevalence of
      elderly populations in Zhejiang was 20.7% and the AD prevalence was 4.5%. The
      patient's gender, age, education level, nature of work, sleep status, marital
      status, whether or not participating in physical exercise, having smoking and
      drinking habits, whether combined with hypertension and diabetes for MCI
      prevalence of the elderly were statistically significant (P < 0.05). CONCLUSION:
      We should pay attention to take appropriate measures in preventing the cognitive
      decline for populations as elderly, especially for women, senior, no spouse,
      engaged in manual labor, low education level, poor quality of sleep and no
      physical exercise, with smoking and drinking, combined with hypertension and
      diabetes.

PMID- 24016439
TI  - [Effect of air pollution on coronary heart disease mortality in Tianjin, 2001
      2009: a time-series study].
AB  - OBJECTIVE: To quantitatively explore the effect of air pollution on coronary
      heart disease mortality in Tianjin. METHODS: Mortality data in 2001 - 2009 were
      from Tianjin mortality surveillance system operated by the Tianjin Centers for
      Disease Control and Prevention while data related to meteorology and air
      pollution were from the Tianjin Meteorological Bureau and Tianjin Environmental
      Monitoring Station, respectively. Generalized Additive Model (GAM) extended
      Poisson regression was used to examine the relationship between air pollution and
      mortality in Tianjin, under the controlling of time trends, weather, the day of
      week and population etc. RESULTS: The crude coronary heart disease mortality in
      Tianjin increased from year 2001 to 2009, from 105.12/100 000 to 167.03/100 000.
      The standardized mortality rate of 96.07/100 000 to 105.11/100 000. Air
      pollutants was more strongly associated with coronary heart disease mortality. By
      single GAM analysis, a 10 ug/m(3) increase in SO2, PM10 and NO2, which accounted
      for 1.25% (95%CI: 0.75% - 1.75%), 0.65% (95%CI: 0.51% - 0.79%) and 1.04% (95%CI:
      0.52% - 1.55%) increased in daily mortality. By multiple GAM analysis, a 10
      ug/m(3) increase in SO2 and PM10 which accounted for 0.86% (95%CI: 0.60% - 1.12%)
      and 0.40% (95%CI: 0.06% - 0.75%) increased the daily mortality. NO2 was not
      significantly associated with coronary heart disease mortality rates, but factors
      as low temperature, low wind speed and population size were (P < 0.05).
      CONCLUSION: from this study showed that air pollution was a risk factor for
      coronary heart disease mortality in Tianjin.

PMID- 24016440
TI  - [Distribution and antibiotics resistance related to nosocomial pathogenic
      bacteria infection in patients after cardiac surgery].
AB  - OBJECTIVE: To investigate the clinical distribution and antibiotics resistance of
      nosocomial infection caused pathogenic bacteria in patients after cardiac
      surgery. METHODS: Clinical data from 612 patients after cardiac surgery under
      microbiologically documented nosocomial infection was retrospectively analyzed
      from January 2007 to December 2012. Identification on related bacterial was
      performed in an automatic ATB Expression system while antimicrobial
      susceptibility was tested by Kirby-Bauer method. RESULTS: were analyzed by
      WHONET5.4. RESULTS: There were 697 strains of clinical pathogenic bacilli
      isolates identified and 421 (60.4%) of them were isolated from sputum while 185
      (26.5%) were from blood. Acinetobacter spp. (124 strains, 17.8%), Pseudomonas
      aeruginosa (85 strains, 12.2%) and Klebsiella pneumoniae (50 strains, 7.2%) were
      the predominant Gram-negative bacilli while S. epidermidis (75 strains, 10.8%)
      was the predominant Gram-positive cocci. The predominant eumycete was Candida
      albicans (43 strains, 6.2%). RESULTS: from the susceptibility test showed that
      carbapenems, cefoperazone/sulbactam and piperacillin/tazobactam were the most
      active antibiotics. The detection of meticillin-resistant Staphylococcus (MRS)
      were 82.9% in S aureus and 95.9% in coagulase negative Staphylococcus. There was
      no Staphylococcus strains resistant to vancomycin found. CONCLUSION: Non
      fermenting Gram-negative bacilli and Staphylococcus appeared the important
      pathogens in patients after cardiac surgery. Drug resistance to antibiotics was
      quite common. Prevention on nosocomial infection and rational use of antibiotics
      remained very important in reducing the amount of drug resistant strains.

PMID- 24016441
TI  - [Risk evaluation on H7N9 avian influenza in Guangzhou, China].
AB  - OBJECTIVE: We conducted both quick surveillance and evaluation programs within
      one week after the novel H7N9 influenza cases had been released by the Ministry
      of Health (MOH), to get the basic information on H7N9 virus in Guangzhou.
      METHODS: We sampled live birds from food markets and the natural habitat of birds
      to detect H7N9, H5 and H9 viruses. We interviewed workers from both markets and
      natural habitats. We also reviewed records on pneumonia patients with unknown
      causes from the surveillance system, to find clues related to the identification
      of severe pneumonia. RESULTS: We sampled 300 specimens from 49 stalls in 13 food
      markets and a natural habitat but none showed H7N9 positive result. A chopping
      block was detected positive of carrying H5 avian influenza virus, while another 4
      specimens including a chicken cage, a duck cage, a chopping block and a pigeon
      cage were detected positive of carrying H9 avian influenza virus. In the past
      month, no sick, dead birds or ILI cases among the workers were discovered. 21.2%
      (7/33) of the stalls did not follow the set regulations for prevention. 10.3%
      (4/39) of the stalls had the cages cleaned, 4 days after the inspection. 3.7%
      (2/54) of the workers wore masks and 40.7% (22/54) of them wore gloves during the
      slaughtering process. 102 bird feces specimens were tested negative on H7N9
      virus. No pneumonia cases with unknown reason were identified. From April 3(rd)
      to 17(th), we found 26 severe pneumonia cases but with negative results on
      influenza A (H7N9). CONCLUSION: According to the data and information from 1) lab
      tests, 2) pneumonia cases with unknown reasons under the surveillance system, 3)
      the identification of severe pneumonia cases, and 4) preventive measures and
      actions taken by the workers, we inferred that no H7N9 virus or related cases
      were found prior to April in Guangzhou. However, the risk of H7N9 epidemic does
      exist because of the following reasons:1) improper market management process, 2)
      negligent behavior of the workers and 3) potential trend of the national
      situation, suggesting strategies related to poultry markets management, health
      education and preventive measures against the avian influenza need to be
      strengthened.

PMID- 24016442
TI  - [Genetic evolution of non-structural gene among avian influenza H5N1 viruses
      isolated from the boundary of Yunnan province].
AB  - OBJECTIVE: To elucidate the characteristics of variation and the genetic
      evolution of non-structural protein (NS1, NS2) genes related to avian influenza
      subtype H5N1 viruses isolated from the boundary region of Yunnan province.
      METHODS: Swab samples were collected from foreign poultry and wild birds in the
      boundary regions of Yunnan province and screened by H5/N1 subtype-specific
      multiplex RT-PCR. The NS segment of H5N1 virus from the positive samples were
      amplified by RT-PCR and cloned into pMD18-T vectors for sequencing. The alignment
      and phylogenetic analysis on those available NS1, NS2 genes were performed with
      sequences of the known reference strains. RESULTS: 71 positive samples were
      identified from 1240 samples, with the positive rate as 5.72%. Fourteen different
      NS segment sequences were obtained from 30 representative positive samples and
      could be divided into 3 distinct clades or sub-clades (I-1, I-2 and II), by
      phylogenetic analysis. The NS1/NS2 genes and Hemagglutinin (HA) genes of H5N1
      viruses from the boundary regions of Yunnan province showed different
      relationships regarding the characteristics on genetic evolution. The
      substitution or mutation of key amino acids sites had been noticed in the nuclear
      location signal domains, effect domain, and other pathogenicity markers.
      CONCLUSION: NS genes of H5N1 subtype viruses in boundary region of Yunnan
      province showed genetic divergence and the virus of clade I-2 and II had become
      dominant epidemic strains in this region since 2010.

PMID- 24016443
TI  - [Study on the complete sequence of CA24 variant isolated during the acute
      hemorrhagic conjunctivitis outbreaks in Zhejiang province during 2002 to 2010].
AB  - OBJECTIVE: To analyze the genetic characteristics of the complete sequence of
      coxsackievirus A24 variant (CA24v) isolated from acute hemorrhagic conjunctivitis
      (AHC) outbreaks in Zhejiang province during 2002 to 2010. METHODS: Complete
      sequences of CA24v epidemic strains isolated in different years were amplified
      under the RT-PCR assay, while the sequences of whole genome, VP1, and 3C region
      of Zhejiang strains were compared with epidemic strains isolated in other areas
      of China and abroad. RESULTS: The whole genome of Zhejiang CA24v strains isolated
      in 2002 and 2010 was 7456 - 7458 bp in length, encoding a polyglutamine protein
      which containing 2214 amino acid residues. There was a insertion with T on site
      97 and 119 within 5'non-coding region between epidemic strain Zhejiang/08/10 and
      strains isolated in 2002. The rates of amino acid homology among Zhejiang/08/10
      and other strains isolated since 2002 were between 94.7% and 100.0%. Compared
      with the representative strains circulated within the recent 60 years, the
      largest average amino acid variations had been occurred on region 2A and 3A, with
      the ratios as 8.4% and 7.3% respectively. The smallest variation happened in
      region 3D, with the ratio only as 1.9%. The rates of stable amino acid variation
      on the whole genome between strains isolated since 1987 and 2002 were 38 and 20.
      P-distance within groups appeared that region 3C was more stable than VP1 of
      strains isolated in 2002 - 2010, and the 3D of early strain Jamaica/10628/87
      might have had a nature of recombination but not observed on those epidemic
      strains in recent years. CONCLUSION: Within the evolution of CA24v strains, the
      time course was more significant than the geographical differences. There had
      been sporadic epidemics of AHC caused by CA24v in Zhejiang province since 2002.

PMID- 24016444
TI  - [Pulsed-field gel electrophoresis typing on non-O157 Shiga toxin-producing
      Escherichia coli isolates].
AB  - OBJECTIVE: To establish a database and to understand the molecular
      epidemiological features of non-O157 Shiga toxin-producing Escherichia coli
      (STEC) isolates from different animal reservoirs and patients. METHODS: Pulsed
      field gel electrophoresis (PFGE) was performed according to the PulseNet protocol
      with minor modifications. A dendrogram was constructed using the BioNumerics.
      RESULTS: Under the PulseNet protocol, 62 PFGE patterns were obtained from 76 non
      O157 STEC isolates and then divided into A to M groups. Isolates from different
      sources were widely distributed in different groups, but were predominant seen in
      certain groups. CONCLUSION: The non-O157 STEC isolates in China were highly
      polymorphic. PulseNet protocol seemed to be suitable for the typing of Chinese
      non-O157 STEC isolates.

PMID- 24016445
TI  - [A systematic review regarding the effects of different kinds of selenium
      supplementations on Kaschin-Beck disease].
AB  - OBJECTIVE: To systematically assess the efficacy of different programs regarding
      the selenium supplementation formulae used for prevention and treatment of
      Kaschin-Beck disease (KBD) in children. METHODS: PubMed, EMBASE, Cochrane
      Library, SCI expanded, CNKI (Chinese National Knowledge Infrastructure), VIP
      (Chinese Science and Technique Journals Database), CBM (The Chinese Biomedical
      Database), Wanfang Database, CSCD (Chinese Science Citation Database) had been
      electronically searched. All the searching processes were up-dated to Dec 2012 to
      identify randomized trials (RCTs) and non-RCTs to compare the selenium
      supplementation formulae with placebo or with no intervention. Two reviewers
      assessed the methodological quality of the study design, including RCTs or non
      RCTs according to Cochrane Handbook for Systematic Reviews of Interventions 5.1
      or a checklist described by Deeks JJ, et al, respectively. Data was extracted
      independently. RESULTS: There were 14 RCTs and 12 non-RCTs papers included, but
      showing low methodological quality. Data from Meta analysis showed that selenium
      supplementation had caused the following progresses: radiologic improvement (RR =
      3.28, 95%CI: 2.06 - 5.22), higher hair selenium (SMD = 2.05, 95%CI: 1.00 - 3.11)
      lower new radiologic lesions (OR = 0.18, 95%CI: 0.09 - 0.36) than in the placebo
      or with no treatment groups. Both selenium and vitamin C supplementation did not
      show differences in radiologic improvement of metaphysis (RR = 1.01, 95%CI: 0.84 
      1.22). Combination of selenium and vitamin E supplementation showed higher
      radiologic improvement than the placebo group. Combination of selenium and
      vitamin C supplementation had no influence on the difference in radiologic
      improvement or hair selenium than selenium supplementation. Selenium-enriched
      yeast showed higher radiologic improvement than sodium selenite (70.83% vs.
      48.84%, P < 0.05). Selenium fertilization showed higher radiologic improvement
      than the non-treatment group (RR = 3.98, 95%CI: 2.25 - 7.05). Comprehensive
      intervention program and 'grain drying approach' also showed certain effects.
      CONCLUSION: Selenium supplementation could lead to better radiologic improvement
      and hair selenium, with lower new radiologic lesions. Current evidence supported
      its benefits on prevention and treatment of KBD. Large sample sized and well
      designed trials together with the reporting on adverse outcome remained
      necessary.

PMID- 24016446
TI  - [Prevalence of suicide ideation among middle school students in China: a
      systematic analysis of studies between 2000 and 2012].
AB  - OBJECTIVE: To analyze the prevalence and differences between gender and grades of
      suicide ideation among middle school students in China from 2000 to 2012 so as to
      provide basis for suicide prevention among middle school students. METHODS:
      Electronic search strategy was carried out, using PubMed, Wanfang Database, VIP
      Database, China National Knowledge Infrastructure (CNKI) and CBM to collect data
      on suicide ideation among middle school students. Fixed effects model or random
      effects model was employed according to statistical tests for the homogeneity.
      Publication bias was assessed by rank correlation test. RESULTS: 40 papers were
      included for meta-analysis, with a total sample size of 320 375. The combined
      prevalence of suicide ideation was 17.99% (95%CI: 16.59% - 19.49%). Prevalence
      rates of suicide ideation were stratified by factors as gender and grade at
      school. Pooled prevalence rates on suicide ideation were as follows: 14.71%
      (95%CI: 13.42% - 16.11%) and 19.92% (95%CI: 19.30% - 21.64%), P < 0.05 for boys
      and girls;16.94% (95%CI: 15.35% - 18.66%) and 19.01% (95%CI: 17.23% - 20.93%), P
      < 0.05 for senior or junior high school students, respectively. CONCLUSION: There
      were differences in the prevalence of suicide ideation among middle school
      students between genders and grades in China.

PMID- 24016447
TI  - [Risk factors related to mental disorder in patients with craniocerebral injury].
AB  - OBJECTIVE: To explore the correlation between mental disorder and craniocerebral
      injury, and notifying its related risk factors. METHODS: 342 patients from Sep.
      2008 to Sep. 2012 with craniocerebral injury were selected and related clinical
      data on general their conditions, including sex, age, educational level,
      satisfaction on careers and relations to family were collected. All the patients
      received CT-scans to the head, IQ test, MQ test, SCID-1/P, PDQC and SCICP
      detection. Multivariate logistic regression was used to analyze the general
      information and cerebral injurious conditions of patients regarding the incidence
      of mental disorders. RESULTS: 249 patients with mental disorder were noticed out
      of the total 342 patients with craniocerebral injury, with the incidence rate as
      72.8% including 117 depression (47.0%), 95 anxiety disorders (38.2%), 27 mania
      (10.8%), 69 intelligence and memory disorders (27.7%) cases. Data from
      correlation analysis showed that factors as sex, age, educational level,
      satisfaction on careers and family of patients as well as type, severity and
      location of the craniocerebral injuries appeared to have important correlation
      with mental disorder. RESULTS: also showed that the age of patients (OR > 1.04),
      severity and location of the craniocerebral injuries (OR1 > 1.28, OR2 > 1.31)
      were independent risk factors (P < 0.05). CONCLUSION: The age of patients,
      severity and location of the craniocerebral injuries were independent risk
      factors for mental disorder in patients with craniocerebral injury.

PMID- 24016448
TI  - [Clinical investigation on schistosomiasis after a 16-year-interruption program
      regarding its transmission, in Jiaxing region of Zhejiang province].
AB  - OBJECTIVE: To investigate the epidemic pattern, diagnosis and treatment of
      schistosomiasis after the 16-years intervention program on its transmission in
      Jiaxing region of Zhejiang province. METHODS: Clinical data of schistosomiasis
      patients during the last 10 years and pathological specimens with deposited
      schistosomal eggs during the last 8 years were retrospectively analyzed. RESULTS:
      The total numbers of schistosomiasis patients admitted to hospital increased from
      194 in 2001 to 960 in 2010, and from 78 to 266 with complications. Number of the
      ones with accompanied diseases increased from 116 to 694. All the numbers of the
      above said three groups showed an yearly increase. The hardest hit age of the
      patients was between 60 and 74. The number of specimens with deposited
      schistosomal eggs increased from 192 in 2003 to 298 in 2010. While the ratio of
      specimens with deposited schistosomal eggs to the total number of pathological
      specimens became slightly decreasing, the average age of patients increased. Eggs
      were mainly deposited on appendix, colon, rectum, stomach, liver, gallbladder and
      small intestine. CONCLUSION: Schistosomiasis still hit the Jiaxing region, with
      the average age of patients increased.

PMID- 24016449
TI  - [Early detection on the onset of scarlet fever epidemics in Beijing, using the
      Cumulative Sum].
AB  - Based on data related to scarlet fever which was collected from the Disease
      Surveillance Information Reporting System in Beijing from 2005 to 2011, to
      explore the efficiency of Cumulative Sum (CUSUM) in detecting the onset of
      scarlet fever epidemics. Models as C1-MILD (C1), C2-MEDIUM (C2) and C3-ULTRA (C3)
      were used. Tools for evaluation as Youden's index and detection time were
      calculated to optimize the parameters and optimal model. Data on 2011 scarlet
      fever surveillance was used to verify the efficacy of these models. C1 (k = 0.5,
      H = 2sigma), C2 (k = 0.7, H = 2sigma), C3 (k = 1.1, H = 2sigma) appeared to be
      the optimal parameters among these models. Youden's index of C1 was 83.0% and
      detection time being 0.64 weeks, Youden's index of C2 was 85.4% and detection
      time being 1.27 weeks, Youden's index of C1 was 85.1% and detection time being
      1.36 weeks. Among the three early warning detection models, C1 had the highest
      efficacy. Three models all triggered the signals within 4 weeks after the onset
      of scarlet fever epidemics. The early warning detection model of CUSUM could be
      used to detect the onset of scarlet fever epidemics, with good efficacy.

PMID- 24016450
TI  - [How to write high-quality epidemiological research paper I. Statement of genetic
      risk prediction studies (GRIPS) -introduction and explanation].

PMID- 24016451
TI  - [Hepatitis E in children].

PMID- 24016452
TI  - Microencapsulated sodium selenite supplementation in dairy cows: effects on
      selenium status.
AB  - The objective of this study was to compare the efficiency of transfer of selenium
      (Se) to plasma and milk from inorganic sodium selenite, either free or
      microencapsulated, and from selenized yeast in dairy cows. The study consisted of
      an in situ-nylon bags incubation, and in an in vivo experiment to compare the Se
      status of cows supplemented with either sodium selenite, microencapsulated sodium
      selenite, or Se yeast. Thirty dairy cows, divided in five groups, were fed the
      following diets: the control group (CTR) received a total mixed ration
      supplemented with sodium selenite in order to have 0.3 mg/kg DM of total Se; 0.3M
      and 0.5M groups received the same control diet supplemented with lipid
      microencapsulated sodium selenite to provide 0.3 and 0.5 mg/kg DM of total Se,
      respectively; 0.3Y and 0.5Y groups received selenized yeast to provide 0.3 and
      0.5 mg/kg of total Se, respectively. Cows were fed the supplements for 56 days
      during which milk, blood, and fecal samples were collected weekly to conduct
      analysis of Se and glutathione peroxidase (GSH-px) activity. Se concentration in
      the nylon bags was assessed to 72%, 64%, and 40% of the initial value (time 0)
      after 4, 8, and 24 h of incubation, respectively. In vivo, cows supplemented with
      0.3 mg/kg of microencapsulated Se had higher milk Se concentration compared to
      CTR. The increment was more pronounced at the highest inclusion rate (0.5 mg/kg,
      0.5M group). GSH-px activity was not significantly affected by treatments. The
      results indicate that lipid microencapsulation has the potential to protect
      nutrients from complete rumen reduction and that Se from microencapsulated
      selenite is incorporated in milk more efficiently than the free form.
      Microencapsulated sodium selenite was shown to be comparable to Se-yeast in terms
      of availability and incorporation in milk when fed at 0.3 mg/kg DM, whereas the
      inclusion in the diet at 0.5 mg/kg DM resulted in higher plasma and milk
      concentrations than selenized yeast. 

PMID- 24016453
TI  - Prevalence of hepatitis B and C viral co-infections among HIV-1 infected
      individuals in Nairobi, Kenya.
AB  - BACKGROUND: Hepatitis B virus (HBV) and Hepatitis C virus (HCV) co-infections
      among HIV-1 infected individuals are growing worldwide health problems
      characterized by lack of effective vaccines, need for expensive treatment,
      chronicity of morbidity and associated mortality. Their prevalence and
      distribution patterns continue to vary across geographical locations with high
      prevalence being detected among high risk populations. To determine the
      prevalence of HBV and HCV among HIV-1 infected individuals, blood samples were
      collected from consenting study subjects visiting comprehensive HIV clinics in
      Nairobi during the period between October and December 2009. METHODS: Blood
      samples from volunteers were screened with ELISA tests for detecting HIV, HBV
      surface antigen (HBsAg) and anti-HCV antibodies. RESULTS: In a total of three
      (300) hundred infected individuals consisting of 129 (43%) males and 171 (57%)
      females 15.3% (46/300) were HIV-1 co-infected with either HBV or HCV or both,
      10.3% (31/300) with HIV-1 and HCV and 6% (18/300) with HIV-1 and HBV infections.
      However, only three individuals (1%) were coinfected with the three viruses
      (HIV/HBV/HCV). CONCLUSION: Though, low levels of co-infection with all three
      viruses were reported, there could be higher prevalence rates than reported here
      especially among high risk populations.

PMID- 24016455
TI  - Severe obesity in children and adolescents: identification, associated health
      risks, and treatment approaches: a scientific statement from the American Heart
      Association.
AB  - Severe obesity afflicts between 4% and 6% of all youth in the United States, and
      the prevalence is increasing. Despite the serious immediate and long-term
      cardiovascular, metabolic, and other health consequences of severe pediatric
      obesity, current treatments are limited in effectiveness and lack widespread
      availability. Lifestyle modification/behavior-based treatment interventions in
      youth with severe obesity have demonstrated modest improvement in body mass index
      status, but participants have generally remained severely obese and often
      regained weight after the conclusion of the treatment programs. The role of
      medical management is minimal, because only 1 medication is currently approved
      for the treatment of obesity in adolescents. Bariatric surgery has generally been
      effective in reducing body mass index and improving cardiovascular and metabolic
      risk factors; however, reports of long-term outcomes are few, many youth with
      severe obesity do not qualify for surgery, and access is limited by lack of
      insurance coverage. To begin to address these challenges, the purposes of this
      scientific statement are to (1) provide justification for and recommend a
      standardized definition of severe obesity in children and adolescents; (2) raise
      awareness of this serious and growing problem by summarizing the current
      literature in this area in terms of the epidemiology and trends, associated
      health risks (immediate and long-term), and challenges and shortcomings of
      currently available treatment options; and (3) highlight areas in need of future
      research. Innovative behavior-based treatment, minimally invasive procedures, and
      medications currently under development all need to be evaluated for their
      efficacy and safety in this group of patients with high medical and psychosocial
      risks. 

PMID- 24016456
TI  - WITHDRAWN: The history of Croatian Trauma Society-A brief overview.
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- 24016454
TI  - Causes of death and influencing factors in patients with atrial fibrillation: a
      competing-risk analysis from the randomized evaluation of long-term anticoagulant
      therapy study.
AB  - BACKGROUND: Atrial fibrillation is associated with increased mortality, but the
      specific causes of death and their predictors have not been described among
      patients on effective anticoagulant therapy. METHODS AND RESULTS: The Randomized
      Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial randomized 18 113
      patients (age, 71.5 +/- 9 years; male, 64%; CHADS2 score, 2.1 +/- 1) to receive
      dabigatran or warfarin. Median follow-up was 2 years, and complete follow-up was
      achieved in 99.9% of patients. All deaths were categorized by the investigators
      using prespecified definitions followed by central adjudication. Overall, 1371
      deaths occurred (annual mortality rate, 3.84%; 95% confidence interval [CI], 3.64
      4.05). Cardiac deaths (sudden cardiac death and progressive heart failure)
      accounted for 37.4% of all deaths, whereas stroke- and hemorrhage-related deaths
      represented 9.8% of the total mortality. An examination of the causes of death
      according to dabigatran or warfarin showed that dabigatran significantly reduced
      vascular (embolism and hemorrhage-related) mortality (relative risk, 0.63; 95%
      CI, 0.45-0.88; P=0.007), whereas other causes of death were similar between
      treatments, including cardiac mortality (relative risk, 0.96; 95% CI, 0.80-1.15;
      P=0.638). The two strongest independent predictors of cardiac death in this
      population were heart failure (hazard ratio, 3.02; 95% CI, 2.45-3.73; P<0.0001),
      and prior myocardial infarction (hazard ratio, 2.05; 95% CI, 1.61-2.62;
      P<0.0001). CONCLUSIONS: The majority of deaths are not related to stroke in a
      contemporary anticoagulated atrial fibrillation population. These results
      emphasize the need to identify interventions beyond effective anticoagulation to
      further reduce mortality in atrial fibrillation. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00262600.

PMID- 24016457
TI  - Simultaneous anterior and posterior compression of the pelvic ring with external
      fixation using a pre-tensed curved bar: A biomechanical study.
AB  - INTRODUCTION: External fixators continue to be essential tools in the urgent
      treatment of pelvic fractures for compression and stabilization of the pelvic
      ring. Current systems fail to produce simultaneous anterior and posterior
      compression. A modified application of an existing curved bar fixator is proposed
      using a specifically designed tensioner to pre-tense the bar prior to its
      connection to Schanz screws. Subsequent pre-tension release and elastic recovery
      of the bar could potentially compress the pelvis. The aim of this work was to
      determine if the modified application could produce greater simultaneous
      compression across the sacroiliac joint and the symphysis of an unstable
      fractured pelvis than the standard application without pretension. MATERIALS AND
      METHODS: Six synthetic pelvis models with symphyseal and unilateral sacroiliac
      joints disruptions, simulating a Tile type C pelvic ring fracture, were used.
      Each specimen was stabilized using two 5mm*250mm supra-acetabular Schanz pins, a
      couple of open adjustable clamps and a semicircular carbon fibre rod applied
      without and with pre-tension. Two distances from bar to bone and three levels of
      pretension were compared. Each pelvis was tested with the six possible parameter
      combinations. Compressive forces at the disrupted joints were measured using
      pressure sensitive film sensors. RESULTS: The modified application produced
      forces significantly higher than the minimal compression achieved with standard
      application. At the sacroiliac joint, after pre-tension release, mean compressive
      forces measured ranged from 28.7 to 85.6N. The closest bar-to-bone distance
      always produced a significantly higher force; similarly, a significant increase
      in compression was found as the pre-tension level rose. At the symphysis, mean
      compressive forces between 35.3N and 49.0N were determined. No significant
      variations were seen with changes of any of the two factors analyzed CONCLUSIONS:
      To pre-tense a semi-circular bar before its use for external fixation of the
      fractured pelvis, is an effective means of applying compression simultaneously
      through the sacroiliac joint and the symphysis. The proposed method generates the
      highest compressive forces at the sacroiliac joint when the rod is subject to the
      highest pre-tension level not producing subluxation and is subsequently
      positioned as close as possible to the bone depending on patient's condition.

PMID- 24016458
TI  - Repairing the annular ligament is not necessary in the operation of Mason type 2,
      3 isolated radial head fractures if the lateral collateral ligament is intact:
      Minimum 5 years follow-up.
AB  - INTRODUCTION: The repair of annular ligament after open reduction and internal
      fixation of radial head fracture could produce the irritation or crepitation
      during range of motion exercise. The purpose of this study is to evaluate the
      significance of unrepaired annular ligament during fixation of isolated radial
      head fractures. MATERIALS AND METHODS: Retrospectively we reviewed the twenty
      five patients who underwent surgical fixation with a plate for Mason type 2, 3
      isolated radial head fracture without annular ligament repair. All the radial
      head fracture did not have the associated injuries which could cause the elbow
      instabilities. The average length of follow-up was 6.9 years. The outcomes were
      evaluated clinically (range of motions, instabilities, pain VAS, Broberg & Murrey
      functional rating score, DASH score) and radiographically (bony union, arthritic
      change, lateral translation of the radial head, humero-ulnar angle with maximum
      varus stress of elbow, ulnar variance). RESULTS: The range of motions between
      affected and contralateral side were not significantly different at last follow
      up. No one showed the instabilities of elbow. The mean pain VAS, Broberg & Murrey
      functional rating score, and DASH score were 2.7+/-0.5, 95.3+/-2.5, and 14.8+/
      5.3 points respectively. Bony union was observed for all cases. There was no
      significant difference in the lateral translation of the radial head, humero
      ulnar angle with maximum varus stress of elbow, and ulnar variance between the
      affected and the contralateral arm. CONCLUSION: The isolated role of the annular
      ligament seems overestimated. We scrutinize that the annular ligament repair is
      not essential in the operative treatment of isolated radial head fractures if the
      lateral collateral ligament is intact.

PMID- 24016460
TI  - From helix to hematology: introduction to a collection of reviews on the emerging
      role of next-generation sequencing in hematology.

PMID- 24016459
TI  - Exposure to UV radiation and risk of Hodgkin lymphoma: a pooled analysis.
AB  - Ultraviolet radiation (UVR) exposure has been inversely associated with Hodgkin
      lymphoma (HL) risk, but only inconsistently, only in a few studies, and without
      attention to HL heterogeneity. We conducted a pooled analysis of HL risk focusing
      on type and timing of UVR exposure and on disease subtypes by age, histology, and
      tumor-cell Epstein-Barr virus (EBV) status. Four case-control studies contributed
      1320 HL cases and 6381 controls. We estimated lifetime, adulthood, and childhood
      UVR exposure and history of sunburn and sunlamp use. We used 2-stage estimation
      with mixed-effects models and weighted pooled effect estimates by inverse
      marginal variances. We observed statistically significant inverse associations
      with HL risk for UVR exposures during childhood and adulthood, sunburn history,
      and sunlamp use, but we found no significant dose-response relationships. Risks
      were significant only for EBV-positive HL (pooled odds ratio, 0.56; 95%
      confidence interval, 0.35 to 0.91 for the highest overall UVR exposure category),
      with a significant linear trend for overall exposure (P = .03). Pooled relative
      risk estimates were not heterogeneous across studies. Increased UVR exposure may
      protect against HL, particularly EBV-positive HL. Plausible mechanisms involving
      UVR induction of regulatory T cells or the cellular DNA damage response suggest
      opportunities for new prevention targets. 

PMID- 24016461
TI  - CD44v6-targeted T cells mediate potent antitumor effects against acute myeloid
      leukemia and multiple myeloma.
AB  - Genetically targeted T cells promise to solve the feasibility and efficacy
      hurdles of adoptive T-cell therapy for cancer. Selecting a target expressed in
      multiple-tumor types and that is required for tumor growth would widen disease
      indications and prevent immune escape caused by the emergence of antigen-loss
      variants. The adhesive receptor CD44 is broadly expressed in hematologic and
      epithelial tumors, where it contributes to the cancer stem/initiating phenotype.
      In this study, silencing of its isoform variant 6 (CD44v6) prevented engraftment
      of human acute myeloid leukemia (AML) and multiple myeloma (MM) cells in
      immunocompromised mice. Accordingly, T cells targeted to CD44v6 by means of a
      chimeric antigen receptor containing a CD28 signaling domain mediated potent
      antitumor effects against primary AML and MM while sparing normal hematopoietic
      stem cells and CD44v6-expressing keratinocytes. Importantly, in vitro activation
      with CD3/CD28 beads and interleukin (IL)-7/IL-15 was required for antitumor
      efficacy in vivo. Finally, coexpressing a suicide gene enabled fast and efficient
      pharmacologic ablation of CD44v6-targeted T cells and complete rescue from
      hyperacute xenogeneic graft-versus-host disease modeling early and generalized
      toxicity. These results warrant the clinical investigation of suicidal CD44v6
      targeted T cells in AML and MM. 

PMID- 24016463
TI  - Neuroimaging biomarkers for Alzheimer's disease in asymptomatic APOE4 carriers.
AB  - INTRODUCTION: The E4 allele of the apolipoprotein E (APOE4) is the major known
      genetic risk factor for Alzheimer's disease (AD), with a dramatic increase in the
      risk of developing AD as the number of APOE4 alleles increases from 0 to 2. For
      this reason, asymptomatic APOE4 carriers as a group offer a great opportunity to
      search for the presence of early biomarkers for AD. The present article reviews
      neuroimaging studies on APOE4 carriers, focusing on cognitively normal
      individuals and on the main neuroimaging biomarkers for AD, i.e. atrophy with
      structural MRI, hypometabolism with FDG-PET, and amyloid deposition with amyloid
      PET imaging. STATE OF THE ART: There are a great number of studies on the effect
      of APOE4 on brain structures, and they tend to show significant atrophy in APOE4
      carriers compared to non-carriers especially in regions susceptible to AD
      pathology such as the hippocampus. However, results are rather discrepant which
      suggests that the effect of APOE4 on brain structure is subtle. As for FDG-PET
      metabolism, the few available studies show decreased metabolism, again especially
      in AD-sensitive regions such as posterior associative parietal areas, with a dose
      dependent effect (i.e. worsening as the number of APOE4 alleles increases).
      Finally, there is a unanimous and major effect of APOE4 on amyloid deposition
      with an increase in Abeta load as the number of APOE4 alleles increases and a
      decrease in the age of predicted amyloid-positivity in APOE4 carriers. This
      graded effect of APOE4 on atrophy, hypometabolism, and amyloid deposition is
      consistent with multimodal neuroimaging studies suggestive of a predominant
      effect of APOE4 on amyloid rather than tau-related injury and on brain metabolism
      rather than brain structure. Neuroimaging studies also suggest that APOE4 effects
      may be mediated by both Abeta-dependent and Abeta-independent pathological
      processes. This contradicts the view that Abeta pathology is a necessary upstream
      event to neuronal injury in AD. PERSPECTIVES AND CONCLUSION: Future studies
      should tell whether the mechanisms and sequences evidenced in carriers are
      comparable to those found in non-carriers, but it is likely that APOE4 not only
      influences the risk for AD, but also modulates the pathophysiological cascade.
      Altogether, APOE4 carriers offer a great opportunity to investigate brain changes
      in the asymptomatic stages of AD and to further our understanding of the
      pathophysiology of the disease, although precaution is needed for interpretation
      in AD at large.

PMID- 24016462
TI  - Disease severity in familial cases of IBD.
AB  - BACKGROUND: Phenotypic traits of familial IBD relative to sporadic cases are
      controversial, probably related to limited statistical power of published
      evidence. AIM: To know if there are phenotype differences between familial and
      sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983
      cases. METHODS: 5783 patients (48.3%) had ulcerative colitis (UC) and 6200
      (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree
      relatives affected by UC/CD were defined as familial case. RESULTS: In UC and CD,
      familial cases compared with sporadic cases had an earlier disease onset (UC: 33
      years [IQR 25-44] vs 37 years [IQR 27-49]; p<0.0001); (CD: 27 years [IQR 21-35]
      vs 29 years [IQR 22-40]; p<0.0001), higher prevalence of extraintestinal immune
      related manifestations (EIMs) (UC: 17.2% vs 14%; p=0.04); (CD: 30.1% vs 23.6%;
      p<0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs
      51.8%; p=0.0001), penetrating behavior (21% vs 17.6%; p=0.01) and perianal
      disease (32% vs 27.1%; p=0.003). Differences are not influenced by degree of
      consanguinity. CONCLUSION: When a sufficiently powered cohort is evaluated,
      familial aggregation in IBD is associated to an earlier disease onset, more EIMs
      and more severe phenotype in CD. This feature should be taken into account at
      establishing predictors of disease course.

PMID- 24016465
TI  - Disease-specific adaptive immune biomarkers in Alzheimer's disease and related
      pathologies.
AB  - Identification of disease-specific diagnostic and prognostic biomarkers allowing
      for an early characterization and accurate clinical follow-up of Alzheimer's
      disease (AD) patients is a major clinical objective. Increasing evidences
      implicate both humoral and cellular adaptive immune responses in the
      pathophysiology of AD. Such disease-related B- and T-cell responses constitute a
      promising source of potential specific early biomarkers. Among them, levels of
      anti-Abeta antibodies in the serum and/or cerebrospinal fluid of patients may
      correlate with AD progression, clinical presentation of the disease, and
      occurrence of associated pathologies related to cerebral amyloid angiopathy. In
      the same line, Abeta-specific T cell responses and immune regulatory populations
      implicated in their modulation appear to play a role in the pathophysiology of AD
      and cerebral amyloid angiopathy. Further characterization of both autoantibodies
      and T cell responses specific for disease-related proteins, i.e. Abeta and
      hyperphosphorylated Tau, will allow better deciphering their interest as early
      diagnostic and prognostic markers in AD. Biomarkers of adaptive immune responses
      specific for other pathological proteins may also apply to other neurological
      disorders associated with abnormal protein deposition. 

PMID- 24016464
TI  - Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial.
AB  - The Dominantly Inherited Alzheimer's Network Trials Unit (DIAN-TU) was formed to
      direct the design and management of interventional therapeutic trials of
      international DIAN and autosomal dominant Alzheimer's disease (ADAD)
      participants. The goal of the DIAN-TU is to implement safe trials that have the
      highest likelihood of success while advancing scientific understanding of these
      diseases and clinical effects of proposed therapies. The DIAN-TU has launched a
      trial design that leverages the existing infrastructure of the ongoing DIAN
      observational study, takes advantage of a variety of drug targets, incorporates
      the latest results of biomarker and cognitive data collected during the
      observational study, and implements biomarkers measuring Alzheimer's disease (AD)
      biological processes to improve the efficiency of trial design. The DIAN-TU trial
      design is unique due to the sophisticated design of multiple drugs, multiple
      pharmaceutical partners, academics servings as sponsor, geographic distribution
      of a rare population and intensive safety and biomarker assessments. The
      implementation of the operational aspects such as home health research delivery,
      safety magnetic resonance imagings (MRIs) at remote locations, monitoring
      clinical and cognitive measures, and regulatory management involving multiple
      pharmaceutical sponsors of the complex DIAN-TU trial are described. 

PMID- 24016466
TI  - Clinical indications for analysis of Alzheimer's disease CSF biomarkers.
AB  - The cerebrospinal fluid (CSF) biomarkers beta-amyloid1-42 (Abeta1-42), total tau
      protein (T-tau) and hyperphosphorylated tau (P-tau181P) are well-validated and
      are increasingly used in clinical practice as an affirmative diagnostic tool for
      Alzheimer's disease (AD). These biomarkers have also been implemented in the
      revised diagnostic criteria of AD. The combination of the CSF biomarkers Abeta1
      42, T-tau and P-tau181P results in high levels of sensitivity, specificity and
      diagnostic accuracy for discriminating AD from controls (including psychiatric
      disorders like depression). These biomarkers can be applied for diagnosing AD in
      the prodromal phase of the disease (mild cognitive impairment). In case of doubt
      between vascular dementia (VaD) or mixed AD-VaD pathology in dementia patients,
      the determination of CSF Abeta1-42, T-tau and P-tau181P levels is of help to
      confirm or exclude the AD component in the pathophysiology of the dementia
      syndrome. However, their discriminatory power for the differential diagnosis of
      dementia is suboptimal. Other CSF biomarkers like Abeta1-40, and those that are
      reflective of the pathology of non-AD dementias, could improve the accuracy of
      differential dementia diagnosis. The added differential diagnostic value of the
      CSF biomarkers Abeta1-42, T-tau and P-tau181P could lie within those cases in
      which the routine clinical diagnostic work-up is not able to discriminate between
      AD or non-AD dementias. In summary, the CSF biomarkers Abeta1-42, T-tau and P
      tau181P can be used in clinical practice to discriminate AD from healthy aging
      (including psychiatric disorders like depression), to diagnose AD in its
      prodromal phase or in atypical forms with prominent non-memory impairment, to
      identify AD in patients with mixed pathologies and in case of an ambiguous (AD
      versus non-AD) dementia diagnosis. 

PMID- 24016467
TI  - The frequency of and reasons for acute hospital transfers of older nursing home
      residents.
AB  - The purpose of the study was to examine the frequency of and reason for transfer
      from nursing homes to the emergency department (ED), whether these transfers led
      to admission to a hospital ward, and whether the transfer rate differs as a
      function of type of nursing home provider and to identify the frequency of
      avoidable hospitalizations as defined by the Swedish Association of Local
      Authorities and Regions (SALAR). The design was retrospective, descriptive. Data
      were collected in a Swedish municipality where 30,000 inhabitants are 65 years or
      older. Structured reviews of the electronic healthcare records were performed.
      Included were residents living in a nursing home age 65+, with healthcare records
      including documented transfers to the ED during a 9-month period in 2010. The
      transfer rate to the ED was 594 among a total of 431 residents (M=1.37 each). 63%
      resulted in hospitalization (M=7.12 days). Nursing home's transfer rate differed
      between 0.00 and 1.03 transfers/bed and was higher for the private for-profit
      providers than for public/private non-profit providers. One-fourth of the
      transfers were caused by falls and/or injuries, including fractures. The
      frequency of avoidable hospitalizations was 16% among the 375 hospitalizations.
      The proportion of transfers to the ED ranged widely between nursing homes. The
      reasons for this finding ought to be explored. 

PMID- 24016469
TI  - Fukushima remediation: status and overview of future plans.
AB  - The 2011 accident at the Fukushima Dai-ichi Nuclear Power Plant, Japan, released
      large quantities of volatile radionuclides, requiring evacuation of a 20 km zone
      around the reactor site plus additional areas where fallout was particularly
      high. After decay of shorter-lived isotopes, off-site contamination is now
      dominated by (134/137)Cs, with ~1800 km(2) having external gamma doses above 5
      mSv y(-1). Although the significance for health of such radiation levels is low,
      there has been a Government decision that these areas will be cleaned up to
      reduce exposure and allow displaced residents to return home. After initial tests
      at 2 sites, a further 11 demonstration remediation projects have been carried
      out. This work is coordinated by the Japan Atomic Energy Agency (JAEA), with MCM
      providing support in quality assessment of radioactivity measurements, evaluating
      the success of different clean-up methods and developing guidelines for the next
      multi-year phase of large-scale remediation. This work provides a unique
      perspective on the progress of remediation, experience gained and issues that
      still need to be resolved - particularly associated with management of the huge
      quantities of waste generated. This knowledge base will also be important for the
      bigger challenge of on-site remediation, which will require decades to complete.
      Additionally, experience and tools may be transferable to cleaning nuclear legacy
      sites around the world, a problem that is often forgotten in the debate on
      national nuclear waste management. 

PMID- 24016468
TI  - Hyperlipidemia, tissue factor, coagulation, and simvastatin.
AB  - Hyperlipidemia affects millions of people worldwide and is a major risk factor
      for cardiovascular disease. People with hyperlipidemia have elevated levels of
      serum cholesterol and an increased risk of thrombosis. Studies have suggested
      that oxidized lipoproteins, such as oxidized low-density lipoprotein (oxLDL),
      contribute to the development of a pro-thrombotic state. In this review, we
      discuss our recent studies demonstrating a role for hematopoietic cell-derived
      tissue factor (TF) expression in the activation of coagulation and increased
      thrombosis associated with hyperlipidemia. In addition, we investigated the
      effect of simvastatin on TF expression and coagulation. We found that simvastatin
      reduced leukocyte TF expression, TF+ microparticles, and coagulation. These
      results and earlier studies suggest that the anti-coagulant activity of statins
      is due, in part, to their ability to reduce monocyte TF expression in patients
      with cardiovascular disease.

PMID- 24016470
TI  - The C-terminal extension of bacterial flavodoxin-reductases: involvement in the
      hydride transfer mechanism from the coenzyme.
AB  - To study the role of the mobile C-terminal extension present in bacterial class
      of plant type NADP(H):ferredoxin reductases during catalysis, we generated a
      series of mutants of the Rhodobacter capsulatus enzyme (RcFPR). Deletion of the
      six C-terminal amino acids beyond alanine 266 was combined with the replacement
      A266Y, emulating the structure present in plastidic versions of this flavoenzyme.
      Analysis of absorbance and fluorescence spectra suggests that deletion does not
      modify the general geometry of FAD itself, but increases exposure of the flavin
      to the solvent, prevents a productive geometry of FAD:NADP(H) complex and
      decreases the protein thermal stability. Although the replacement A266Y partially
      coats the isoalloxazine from solvent and slightly restores protein stability,
      this single change does not allow formation of active charge-transfer complexes
      commonly present in the wild-type FPR, probably due to restraints of C-terminus
      pliability. A proton exchange process is deduced from ITC measurements during
      coenzyme binding. All studied RcFPR variants display higher affinity for NADP(+)
      than wild-type, evidencing the contribution of the C-terminus in tempering a non
      productive strong (rigid) interaction with the coenzyme. The decreased catalytic
      rate parameters confirm that the hydride transfer from NADPH to the flavin ring
      is considerably hampered in the mutants. Although the involvement of the C
      terminal extension from bacterial FPRs in stabilizing overall folding and bent
      FAD geometry has been stated, the most relevant contributions to catalysis are
      modulation of coenzyme entrance and affinity, promotion of the optimal geometry
      of an active complex and supply of a proton acceptor acting during coenzyme
      binding. 

PMID- 24016471
TI  - [Gestational weight gain and its relationship with the birthweight of offspring].
AB  - OBJECTIVE: To explore the appropriate weight gain during pregnancy and its
      relationship with the birthweight of offspring. METHODS: A total of 16 460
      healthy pregnant women who delivered in Beijing Obstetrics and Gynecology
      Hospital and Haidian Maternity and Child Health Care Hospital in 2010 were
      recruited. All are singleton pregnancies. Conditions of babies and mothers were
      recorded, including maternal age, height, prepregnant weight, pregnant weight,
      gestational weeks on delivery, delivery mode and newborn birthweight. All the
      pregnant women were divided into underweight, normal weight and overweight group
      according to their prepregnant body mass index and the criteria of overweight and
      obesity for Chinese adults.Birthweight between 2500 g and 4000 g was defined as
      normal birthweight, and 2900 g to 3499 g was defined as appropriate
      birthweight.Logistic regression model and receiver operating characteristic (ROC)
      curve analysis were used to explore the recommended gestational weight gain
      (GWG). RESULTS: (1) The average GWG of the 16 460 women was (17.1 +/- 4.9) kg,
      and the average birthweight of the babies was (3406 +/- 400) g. Prevalence of low
      birthweight and macrosomia was 0.92% (152/16 460) and 7.55% (1 242/16 460),
      respectively.GWG of underweight (n = 3089), normal weight (n = 11 478) and
      overweight group (n = 1893) was (17.4 +/- 4.6) kg, (17.3 +/- 4.8) kg and (15.6 +/
      5.3) kg, respectively. And GWG was positively related with the birthweight of
      offspring (P < 0.01).The differences of GWG, neonatal birthweight and macrosomia
      prevalence among the three groups are statistically significant (P < 0.01). (2)
      There are 8449 appropriate birthweight babies in the three groups.For their
      mothers in the underweight, normal weight and overweight group, the recommended
      range of GWG were 14.0-19.5 kg, 13.5-19.5 kg and 11.0-18.0 kg, respectively.The
      recommended GWG for all women was 16.0 kg. (3) According to the recommended GWG,
      low GWG will increase the risk of low birthweight (OR = 1.589, 95% CI: 1.085
      2.326) and reduce the risk of macrosomia (OR = 0.500, 95% CI: 0.401-0.624).
      Excessive GWG will increase the risk of macrosomia (OR = 2.031, 95% CI:1.789
      2.306), but will not lower the risk of low birthweight (OR = 1.168, 95% CI:0.774
      1.764). (4) For the underweight, normal weight and overweight group, the range of
      GWG obtained by the receiver operating characteristic (ROC) curve analysis were
      16.3-16.7 kg, 15.6-17.8 kg and 14.6-15.1 kg.For all the three groups, the range
      was 15.6-16.7 kg.The ranges obtained by the ROC curve analysis were all within
      the recommended range. CONCLUSION: The GWG was positively associated with the
      birthweight of offspring, and the appropriate GWG was around 16.0 kg.

PMID- 24016472
TI  - [Association between single nucleotide polymorphism of macrophage migration
      inhibitory factor-rs1007888 and the pathogenesis of gestational diabetes
      mellitus].
AB  - OBJECTIVE: To investigate the association between single nucleotide polymorphism
      (SNP) of macrophage migration inhibitory factor (MIF) gene-rs1007888 and the
      pathogenesis of gestational diabetes mellitus (GDM). METHODS: A total of 120 GDM
      pregnant women (GDM group) and 165 healthy pregnant women (control group) from
      Affiliated Hospital of Medical College, Qingdao University were recruited from
      June 2011 to July 2012. Their age, gestational week, height and weight were
      recorded. The levels of fasting blood glucose (FBG) and fasting insulin (FIN)
      were determined. Body mass index (BMI), the hemeostasis model assessment-insulin
      resistance (HOMA-IR) and hemeostasis model assessment-beta cell function (HOMA
      beta) were calculated. DNA was extracted from fasting blood samples. SNP of MIF
      rs1007888G/A was determined by DNA sequencing.The FBG, FIN, HOMA-IR and HOMA-beta
      were compared between GDM group and the control group.They were also compared
      among pregnancies with different genotypes. RESULTS: (1) GDM group had higher
      FBG, FIN and HOMA-IR levels, but lower HOMA-beta than the control group (all P <
      0.05). (2) MIF-rs1007888 SNP genotype frequencies of GG, GA and AA were 37.5%,
      45.8% and 16.7%, and the allelic frequencies of G and A were 60.4%, 39.6% in GDM
      group; However, in the control group, the frequencies of GG, GA and AA were
      26.1%, 54.5% and 19.4%, and the allelic frequencies of G and A were 53.3%, 46.7%,
      respectively.The distributions of MIF genotypes in GDM patients were
      significantly different from the healthy subjects (P < 0.05).No significant
      difference of MIF-rs1007888 allele distributions was observed between GDM group
      and the control group (P > 0.05). (3) The FBG, FIN and HOMA-IR in pregnant women
      with GG genotype were statistically higher than those with GA or AA genotypes,
      while HOMA-beta was lower in women with GG genotype (all P < 0.05). CONCLUSIONS:
      The SNP of MIF rs-1007888 was related to the insulin resistance and pancreatic
      beta cell function of pregnant women. GG genotype of MIF-rs1007888 might be a
      genetic susceptible factor in the pathogenesis of GDM.

PMID- 24016473
TI  - [Initial research of serum glycated albumin during pregnancy].
AB  - OBJECTIVE: To explore the normal range of serum glycated albumin (GA) during the
      second trimester in non-gestational diabetes mellitus (GDM) population and the
      value of serum GA in the blood glucose monitoring during pregnancy. METHODS: The
      GA was measured in 101 healthy gravida during the second trimester and 80 gravida
      with GDM and diabetes mellitus who were in treatment at Peking University First
      Hospital between August 2011 and December 2011, in order to analyze the normal
      range of GA and the relationship between GA and the level of blood glucose.
      RESULTS: (1) The normal range of GA during the second trimester was 10.9%-15.3%,
      which was negatively correlated with body mass index (P < 0.01). (2) Significant
      correlations were observed between GA and the level of hemoglobin A1c (HbA1c),
      preprandial, postprandial and mean plasma glucose in gravida with GDM and
      diabetes mellitus (r:0.361, 0.252, 0.338, 0.310;all P < 0.05). (3) When the level
      of GA was 13.97%, the sensitivity and specificity index for glucose control were
      78.0% and 74.4%. CONCLUSIONS: GA could evaluate the severity of disease in
      gravida with GDM and diabetes mellitus. 10.9%-15.3% could be suggested as normal
      range of GA for the gravida at the second trimester.

PMID- 24016474
TI  - [Study on leuprorelin acetate in treatment of uterine adenomyosis with
      infertility].
AB  - OBJECTIVE: To study clinical efficacy of leuprorelin acetate in treatment of
      uterine adenomyosis with infertility. METHODS: From January 1,2011 to March
      31,2012, 166 cycles in 166 infertile patients combined with uterine adenomyosis
      undergoing in vitro fertilization embryo transplant (IVF-ET) with long protocol
      ovum induction by leuprorelin acetate in centre of medical reproduction, ningbo
      women and children's hospital were studied retrospectively. In the mean time, 200
      cycles in 200 infertile patients with tubal factors were enrolled as control
      group.The volume of uterus and outcome of IVF-ET were compared and studied
      between two groups. RESULTS: (1) Volume of uterus:in adenomyosis group, after 2-6
      cycles of injecting leuprorelin acetate (3.75 mg/28 days), the mean uterine
      volume was shrinked from (180 +/- 73) cm(3) to (86 +/- 67) cm(3) (P < 0.05). (2)
      Outcome of IVF-ET:the rate of embryo implantation was 39.1% in adenomyosis group
      and 35.8% in control group. The rate of clinical pregnancy was 54.2% in
      adenomyosis group and 53.7% in control group. The rate of abortion was 4.7% in
      adenomyosis group and 4.2% in control group. They all did not show statistical
      differences (P > 0.05). (3) In adenomyosis group, the rate of fertilization, two
      pronuclear (2PN) and superior embryo were 67.2%(319/475), 60.8% (289/475) and
      52.9% (162/306) in patients with failed pregnancy and 74.2% (423/570), 67.7%
      (386/570) and 62.1% (256/412) in patients with successful pregnancy after IVF-ET,
      which reached significant difference (P < 0.05). CONCLUSION: Leuprorelin acetate
      could improve volume of uterine adenomyosis and outcome of pregnancy in patients
      undergoing IVF-ET.

PMID- 24016475
TI  - [A meta-analysis of preventing bone mineral loss in patients with endometriosis
      treated by gonadotrophin-releasing hormone analogues with add-back therapy].
AB  - OBJECTIVE: To evaluate the role and efficacy of preventing bone mineral loss in
      patients with endometriosis treated by gonadotrophin-releasing hormone analogues
      (GnRH-a) combined with add-back therapy. METHODS: Prospective, randomized
      controlled studies of the use of GnRHa with add-back therapy in treatment of
      endometriosis were enrolled in this study from Medline, Embase, Cochrane library,
      China National Knowledge Internet (CNKI), Chinese Biological Medicine Disk (CBM)
      and Data Base of Wanfang.After quality assessment and data extraction, meta
      analysis were conducted in the change of BMD, reproductive hormone (E2) and
      visual pain score(VAS) by Stata 11.0 software. RESULTS: A total of 785 patients
      from 13 randomized controlled trail (RCT) studies enrolled in this study after
      exclude no following up, poor quality and repeat published studies.377 patients
      were in group of GnRH-a with add-back treatment and 408 patients were in group of
      GnRna alone.The findinds were showed in meta-analysis: (1) there was a
      significant difference in percentage change of bone mineral density (BMD) between
      two groups, the add-back therapy was more effective in prevention of bone loss
      which was (SMD = 0.223, 95%CI:0.003 to 0.443, P = 0.047). (2) There was no
      significant difference in the level of reproductive hormone between two groups
      (SMD = -0.053, 95% CI:-0.479 to 0.373, P = 0.807). (3) There was also no
      significant difference in the visual pain score between the two groups (SMD = 
      0.157, 95% CI: -0.474 to 0.160, P = 0.332). CONCLUSIONS: GnRH-a with add-back
      therapy have been shown to be more effective in preventing loss of BMD than GnRH
      a treatment alone.However, the long term effect of preventing BMD should be
      studied.

PMID- 24016476
TI  - [Diagnostic approaches of cervical glandular intraepithelial neoplasia].
AB  - OBJECTIVE: To investigate diagnostic approaches of cervical glandular
      intraepithelial neoplasia (CGIN) for improving the diagnostic levels of CGIN.
      METHODS: Clinical data of 106 cases with CGIN admitted in hospital from Jan.2008
      to Dec. 2010 were analyzed retrospectively.All data from preoperative thin-prep
      cytologic test (TCT), cervical biopsies and postoperative pathological
      examination of the excised cervical tissues were reviewed. RESULTS: Among 106
      patients, 62 cases (58.5%, 62/106) were low grade CGIN (L-CGIN), 44 cases (41.5%,
      44/106) were high grade CGIN (H-CGIN); 25 cases (23.6%, 25/106) were pure CGIN
      and 81 cases (76.4%, 81/106) were CGIN mixed with cervical intraepithelial
      neoplasia (CIN). Fifteen cases (14.2%, 15/106) were found atypical glandular cell
      (AGC) by TCT. In the 15 cases, there were 4 cases (6.5%, 4/62) L-CGIN, and 11
      cases (25.0%, 11/44) H-CGIN, there was significant difference between the two
      groups (P < 0.05); among 15 cases with AGC, 11 cases of them (44.0%, 11/25) were
      pure CGIN, 4 cases (4.9%, 4/81) mixed with CIN, in which there were significant
      difference (P < 0.01).Seven cases (25.0%, 7/28) were detected glandular lesions
      in 28 cases by endocervical curettage (ECC). Totally 23 cases (22.8%, 23/101)
      were detected CGIN by colposcopy-directed biopsy, 11 cases (19.0%, 11/58) were
      with L-CGIN, 12 cases (27.9%, 12/43) H-CGIN, there was no significant difference
      between them (P > 0.05).Among the 23 cases, 13 cases (52.0%, 13/25) were pure
      CGIN, 10 cases (12.3%, 10/81) CGIN mixed with CIN, which showed significant
      difference (P < 0.01). All 106 patients were treated, 101 cases treated with
      cervical conization and 5 cases performed hysterectomy; 23 cases were diagnosed
      CGIN preoperation, the ratio of preoperative diagnosis was 21.7% (23/106), 83
      cases (80.3%, 83/106) diagnosed postoperatively. CONCLUSIONS: Routine diagnostic
      methods of CGIN were not satisfaction, most CGIN were diagnosed after cervical
      resection.Cervical conization may play a very important role in diagnosis of
      CGIN.The positivity of TCT in H-CGIN was higher than L-CGIN. There was no
      different in diagnosing different CGIN grades by colposcopy-directed biopsy. The
      ratio of preoperative diagnosis of pure CGIN was higher than those with CGIN
      mixed with CIN.

PMID- 24016477
TI  - [Clinical study of sentinel lymph node detection guided radical abdominal
      trachelectomy].
AB  - OBJECTIVE: To evaluate the clinical value of sentinel lymph nodes (SLN) in
      predicting pelvic lymph node status for early cervical squamous cell carcinoma,
      and approach the clinical significance of SLN detection for guiding radical
      abdominal trachelectomy (RAT).Outcomes of follow up and fertility were also
      observed. METHODS: A total of 31 patients with stageIa2-Ib1 squamous cell
      carcinoma planned to be given RAT and pelvic lymphadenectomy were enrolled.
      (99m)Tc-labeled phytate was injected before surgery.Intraoperatively, SLN were
      identified, excised, and submitted to fast frozen section.Systematic bilateral
      pelvic lymphadenectomy was performed, and then RAT was performed in patients with
      negative SLN. All nodes were sent for routine pathological examination and
      immunostained with anti-cytokeratin antibody to detect micrometastases. RESULTS:
      SLN were detected in all patients (100%,31/31). A total of 109 SLN were
      identified with a mean number of 3.5 per patient.Of these, SLN of 2 patients were
      positive on frozen sections and proved to be metastasis by final pathologic
      examination and quitted the RAT. No missed micrometastasis was found using
      immunohistochemical staining in SLN and other lymph nodes using histologically
      node-negative cases. No false negative cases was found and the negative value was
      100% (31/31). The sensitivity, accuracy, and false negative rates were 100%,
      100%, and 0, respectively. Perioperative complications occurred in 5 patients
      including 2 cases of bladder injury and 3 cases of uterine artery injury.No
      relapses occurred during follow-up.Five of 19 patients with procreative desire
      conceived pregnancies (4 spontaneous abortion and 1 premature birth) after
      surgery. CONCLUSIONS: The identification of SLN using (99m)Tc-labeled phytate
      could predict the pelvic lymph node status in early stage cervical cancer. Under
      the guidance of SLN detection, RAT is a feasible operative modality with well
      prognosis and low complications for young patients who desire to preserve
      reproductive function.

PMID- 24016478
TI  - [Analysis of the security, pregnancy outcomes, and the tumor recurrence related
      factors of young patients with cervical cancer treated with different radical
      trachelectomy].
AB  - OBJECTIVE: To explore the security, pregnancy outcomes, and the tumor recurrence
      related factors of young patients with cervical cancer treated with different
      radical trachelectomy (RT). METHODS: Thirty-two young patients < 40 years of age
      with early cervical cancer from May 2004 to July 2012 admitted in Tumor Hospital
      Xiangya School of Medicine of Central South University were divided into two
      groups based on different operation methods: vaginal radical trachelectomy (RVT)
      group and abdominal radical trachelectomy (RAT) group.The clinical data were
      analyzed by One-way Anova and multivariate Cox stepwise regression analysis.
      RESULTS: The operation duration, number of lymph node dissection, the height of
      the cervical resection, postoperative hospitalization time, incidence of vascular
      injury and incidence of postoperative lymphocele were respectively (250 +/- 82)
      min, 15 +/- 6, (2.31 +/- 0.21) cm, (9.2 +/- 2.9) d, 1/18 and 1/18 in RVT group,
      while (263 +/- 60) min,16 +/- 8, (2.32 +/- 0.26) cm, (10.3 +/- 3.5) d,0 and 1/14
      in RAT group. There was no statistically significant difference between the two
      groups (all P > 0.05). The blood loss (281 +/- 201) ml in RVT group was
      significantly lower than that in the RAT group (492 +/- 320) ml (P < 0.05). The
      length of Vaginal hysterectomy [(2.61 +/- 0.50) cm] and the width of parametrial
      resection [ (2.38 +/- 0.36) cm] in RVT group were significantly less than those
      [(2.95 +/- 0.10), (2.81 +/- 0.22) cm] in the RAT group (all P < 0.05).The
      pregnancy rate between RVT group (3/18) and RAT group (2/14) were no significant
      difference (P > 0.05).One-way Anova analysis showed that the recurrence of early
      cervical cancer was related to tumor size in diameter (F = 4.911, P = 0.047),
      while there were no correlation with age, clinical stage, histological type and
      surgical approach (all P > 0.05).Multivariate analysis showed that tumor diameter
      size was an independent risk factor for tumor recurrence (beta = 0.259, P =
      0.031). CONCLUSIONS: RT for young patients with early cervical cancer is
      feasible.Pregnancy outcomes after RT need to be study in the future. Tumor size
      in diameter is the major risk factor for tumor recurrence.

PMID- 24016479
TI  - [A prospective study of adenosine triphosphate-tumor chemosensitivity assay
      directed chemotherapy in patients with recurrent ovarian cancer].
AB  - OBJECTIVE: To investigate the efficacy of adenosine triphosphate (ATP)-tumor
      chemosensitivity assay (TCA) directed chemotherapy in patients with recurrent
      epithelial ovarian cancer. METHODS: From August 2010 to June 2012, recurrent
      epithelial ovarian cancer patients were prospectively enrollmented in Cancer
      Hospital, Peking Union Medical College,Chinese Academy of Medical Sciences.The
      entry criteria are as follows: (1) Histologically proven to be epithelial ovarian
      cancer. (2) Patients of recurrent ovarian cancer with bidimensionally measurable
      tumor, or ascitic or pleural fluid for testing. (3) Karnofsky performance status
      > 60. (4) A life expectancy of at least more than 6 months.According to patients
      desires, they were assigned into two groups: assay-directed therapy group and
      physician's-choice therapy group, patients' clinical and pathological
      characteristics, response rate to chemotherapy and progression-free survival
      (PFS) were compared between two groups. RESULTS: A total of 113 patients with
      recurrent epithelial ovarian cancer were prospectively enrollmented to assay
      directed chemotherapy (n = 56) or physician's-choice chemotherapy (n = 57).There
      was no difference in median age,types of recurrence, surgical-pathological stage,
      pathological type, tumor grade, times of recurrence, residual disease at
      secondary cytoreductive surgery between assay-directed group and physician's
      choice group. The overall response rate (ORR) and median PFS in the ATP-TCA group
      was 66% (37/56) and 7 months, while the ORR in the control group was 46% (26/57,
      P = 0.037), the median PFS was 4 months (P = 0.040). For platinum-resistant
      patients, the ORR between ATP-TCA directed chemotherapy 59% (16/27) and control
      group 25% (7/28) were significantly different (P = 0.010), and the median PFS
      between two groups were also significantly different (5 months and 2 months,
      respectively, P = 0.003). CONCLUSION: ATP-TCA directed chemotherapy could improve
      ORR and PFS in patients with recurrent epithelial ovarian cancer, especially in
      platinum-resistant patients.

PMID- 24016480
TI  - [Effects of miR-135a on HOXA10 expression, proliferation and apoptosis of ovarian
      cancer cells].
AB  - OBJECTIVE: To investigate the effects of miR-135a on HOXA10 expression,
      proliferation and apoptosis of SKOV3 cells. METHODS: (1) Through computer-aided
      algorithms,the predicted target gene of miR-135a (HOXA10)were determined. (2) miR
      135a mimics, miR-135a inhibitor and negative control were transfected into SKOV3
      cells, respectively.Reverse transcription (RT)-PCR, western blot analysis were
      used to examine the expression levels of HOXA10 at different times (24, 48 and 72
      hours). (3) A luciferase reporter assay was used to confirm the direct regulation
      between miR-135a and HOXA10. (4) SKOV3 cells proliferation at different times
      (24,48 and 72 hours) was detected by methyl thiazolyl tetrazolium (MTT) assay
      [quantified by absorbance(A)]. Western blot was used to examine the expression of
      apoptosis-associated protein bcl-2, bax and caspase-3 in SKOV3 cells after 48
      hours transfection. RESULTS: (1) HOXA10 was predicted to be the target gene of
      miR-135a by computer-aided algorithms. (2) RT-PCR shown that HOXA10 mRNA levels
      were decreased over time (24, 48 and 72 hours) after miR-135a mimics transfection
      in SKOV3 cells (0.94 +/- 0.04 vs 0.78 +/- 0.03 vs 0.70 +/- 0.03, P < 0.05).
      While, the expression of HOXA10 mRNA was increased over time after miR-135a
      inhibitor transfection (1.14 +/- 0.05 vs 1.16 +/- 0.03 vs 2.60 +/- 0.08,P <
      0.05). After transfected with miR-135a mimics or miR-135a inhibitor over 48 and
      72 hours, the HOXA10 expression levels in SKOV3 cells were significantly lower or
      higher than each control group, respectively (all P < 0.01). Western blot
      analysis of HOXA10 expression in SKOV3 cells confirmed the results of RT-PCR
      detected. (3) After cotransfection of miR-135a plasmid and pMIR-REPORT luciferase
      plasmid containing HOXA10, luciferase reporter assays showed that the luciferase
      activity reduced by 67.8% (P < 0.01). (4) MTT showed that SKOV3 cells growth
      after miR-135a mimics transfection for 48 and 72 hours were significantly lower
      than those in control group (0.38 +/- 0.03 vs 0.52 +/- 0.05, 0.67 +/- 0.05 vs
      0.75 +/- 0.06;respectively,all P < 0.05).While, SKOV3 cells transfected with miR
      135a inhibitor for 72 hours grew significantly faster than that in control group
      (0.95 +/- 0.05 vs 0.75 +/- 0.06, P < 0.01). After miR-135a mimics transfection,
      the level of bcl-2 protein was significantly lower than that in control group
      (0.28 +/- 0.06 vs 0.76 +/- 0.09,P < 0.01). The activity of caspase-3 was
      significantly higher than that in control group (115.0 +/- 2.4 vs 95.4 +/- 2.1, P
      < 0.01). While, there was no statistical difference of bax expression (P =
      0.142). However, after miR-135a inhibitor transfection, the expression level of
      bcl-2 protein was significantly higher than that in control group (0.92 +/- 0.03
      vs 0.76 +/- 0.09, P = 0.037) and the activity of caspase-3 was significantly
      lower than that in control group (59.5 +/- 4.1 vs 95.4 +/- 2.1, P < 0.01). There
      was also no statistical difference of bax expression (P = 0.066). CONCLUSION: miR
      135a may play an important role in cell proliferation and apoptosis of ovarian
      cancer cells by regulating HOXA10 and its downstream pathways.

PMID- 24016481
TI  - [Expression and significance of matriptase in ovarian cancer cells with diverse
      metastatic potential].
AB  - OBJECTIVE: To study the expression and significance of matriptase in different
      metastatic potential of human ovarian cancer cells. METHODS: High-metastatic
      human ovarian cancer cell HO8910PM and ovarian cancer cell HO8910 were
      collected.The ability of metastatic of the former was stronger than that of the
      latter. Compared the ability of invasion and migration in HO8910PM and HO8910 by
      scratch assay and by millicell chamber artificial reconstituted basement membrane
      invasion assay. Detected the matriptase mRNA and protein expression levels in
      HO8910PM and HO8910 through reverse transcription(RT)-PCR and immunocytochemistry
      methods. RESULTS: The 24 hours' migration distance (347 +/- 8) um of HO8910PM
      cells were significantly higher than that in HO8910 group (154 +/- 10) um (P <
      0.01);The number of HO8910PM cells that penetrated the matrigel after 24 hours'
      incubation were significantly higher than that in HO8910 group (90.7 +/- 2.1 vs
      63.3 +/- 1.5,P < 0.01). The expression of matriptase mRNA in HO8910PM cells was
      higher than that in HO8910 group (0.72 +/- 0.03 vs 0.38 +/- 0.04,P < 0.01). The
      migration was positively correlated with the matriptase mRNA expression levels (r
      = 0.992, P < 0.01); and the invasiveness was also positively correlated with the
      matriptase mRNA expression levels (r = 0.973, P < 0.01). As far protein level,the
      expression of matriptase protein in HO8910PM cells was higher than that in HO8910
      group (15.6 +/- 0.8 vs 7.6 +/- 1.3,P < 0.01). The migration was positively
      correlated with matriptase protein expression levels (r = 0.971, P < 0.01); And
      the invasiveness was also positively correlated with the matriptase protein
      expression levels (r = 0.958, P < 0.01). CONCLUSIONS: The relationship between
      the expression levels of matriptase and the metastatic of ovarian cancer cells
      may be correlative. The function of matriptase in ovarian cancer cells metastatic
      mechanism still need to be confirmed.

PMID- 24016482
TI  - Prevalence of head deformities in preterm infants at term equivalent age.
AB  - INTRODUCTION: Due to a rising number of head deformities in healthy newborns,
      there has been an increasing interest in nonsynostotic head deformities in
      children over recent years. Although preterm infants are more likely to have
      anomalous head shapes than term newborns, there is limited data available on
      early prevalence of head deformities in preterm infants. AIMS: The purposes of
      the present study were to acquire quantitative data on head shape of preterm
      infants at Term Equivalent Age (TEA), to determine the prevalence of symmetrical
      and asymmetrical head deformities and to identify possible risk factors. METHODS:
      In a cross-sectional study design, Cranial Vault Asymmetry Index (CVAI) and
      Cranial Index (CI) calculated from routine head-scans with a non-invasive laser
      shape digitizer were recorded and categorized in type and severity of deformation
      for three different groups of gestational age. Perinatal and postnatal patient
      data was tested for possible associations. RESULTS: Scans of 195 infants were
      included in the study. CVAI at TEA was higher in very preterm (4.1%) compared to
      term and late preterm infants. Prevalence of deformational plagiocephaly was 38%
      in very preterm infants. CI was lower in very (71.4%) and late (77.2%) preterm
      infants compared to term infants (80.0%). Compared to term babies (11%), a large
      number of very (73%) and late (28%) preterm infants exhibited dolichocephaly at
      TEA. DISCUSSION: Prevalence of symmetrical and asymmetrical head deformities in
      preterm infants is high at TEA. Interventions are required to prevent head
      deformities in preterm infants during the initial hospital stay.

PMID- 24016483
TI  - Effects of inulin and di-D-fructose dianhydride-enriched caramels on intestinal
      microbiota composition and performance of broiler chickens.
AB  - In vitro and in vivo experiments were designed to evaluate the effectiveness of
      laboratory-made di-d-fructose dianhydride (DFA)-enriched caramels. The DFA
      enriched caramels were obtained from d-fructose (FC), d-fructose and sucrose
      (FSC), or d-fructose and beta-cyclodextrin (FCDC). In the in vitro experiment,
      raftilose and all caramels increased (P<0.05) l-lactate concentration and
      decreased (P<0.05) pH. Total short-chain fatty acid concentration was higher
      (P<0.05) than controls in tubes containing raftilose, FSC, FCDC and commercial
      sucrose caramel (CSC). Raftilose, and all caramels tested except FSC and FC (1%),
      increased (P<0.01) lactobacilli log10 number of copies compared with the non
      additive control. FSC, FCDC and CSC increased (P<0.01) the bifidobacteria number
      of copies as compared with controls. All additives, except FCDC, decreased
      (P<0.01) Clostridium coccoides/Eubacterium rectale log number of copies. Compared
      with controls, raftilose, FC and CSC led to lower (P<0.01) Escherichia-Shigella
      and enterobacteria. For the in vivo experiment, a total of 144 male 1-day-old
      broiler chickens of the Cobb strain were randomly assigned to one of the three
      dietary treatments for 21 days. Dietary treatments were control (commercial diet
      with no additive), inulin (20 g inulin/kg diet) and FC (20 g FC/kg diet). Final
      BW of birds fed FC diet was higher (P<0.01) than controls or inulin-fed birds,
      although feed: gain values were not different. Feed intake of chickens fed FC was
      higher (P<0.01) than that of inulin-fed birds but not statistically different
      from controls. Crop pH values were lower (P<0.01) in birds fed FC diet as
      compared with control diet, with inulin-fed chickens showing values not different
      from control- or FC-fed birds. Lower (P<0.05) lactobacilli number of copies was
      determined in the crop, ileum and caeca of birds fed the inulin diet compared
      with the control diet. Inulin supplementation also resulted in lower (P<0.05) C.
      coccoides/E. rectale, bacteroides and total bacteria in caecal contents. Addition
      of FC to broiler diets gave place to lower (P<0.05) enterobacteria and
      Escherichia-Shigella in crop and caecal contents compared with controls. The
      bacteroides number of copies increased (P<0.05) as compared with controls in the
      ileum, but decreased (P<0.05) in the caeca of chickens fed the FC diet. Energy,
      ADF, NDF and non-starch polysaccharides faecal digestibilities were greater
      (P<0.05) than controls in chickens fed diets containing inulin or FC. Fat
      digestibility was higher (P<0.05) in FC-fed birds compared with controls or
      inulin-fed chickens. In conclusion, DFA-enriched caramels tested here,
      particularly FC, may represent a type of new additives useful in poultry
      production. 

PMID- 24016484
TI  - Regional systems of care for ST-elevation myocardial infarction: do they save
      lives?

PMID- 24016485
TI  - Exercise-mediated changes in high-density lipoprotein: impact on form and
      function.
AB  - The goal of this systematic review was to assess the current understanding of the
      effects of exercise intervention on high-density lipoprotein (HDL) cholesterol
      (HDL-C) and changes in HDL function as well as modification of these effects by
      genomic factors. The reviewed studies demonstrate that exercise has modest
      effects on HDL-C with limited data suggesting an effect on HDL function. Genetic
      polymorphisms in proteins associated with HDL metabolism play a role in modifying
      the HDL-C response to exercise and possibly its function. Exercise as an
      intervention for patients at risk for cardiovascular events can lead to small
      improvements in HDL-C and potential changes in HDL function. There is an
      important modifier effect of genetics in determining these changes. 

PMID- 24016486
TI  - Differences in the outcome of patients undergoing percutaneous coronary
      interventions at teaching versus non-teaching hospitals.
AB  - BACKGROUND: Teaching hospitals have superior outcomes for major medical
      conditions including cardiovascular disease compared to non-teaching hospitals.
      This may not be applicable to invasive cardiac procedures given a potential
      increase in complications due to trainee participation. METHODS: We assessed the
      impact of hospital teaching status on the outcome of 89,048 patients who
      underwent percutaneous coronary intervention (PCI). Teaching hospitals were
      defined as trainee involvement in greater than 50% of PCIs conducted at that
      hospital and corresponded to teaching status granted by national accreditation
      agencies. Unadjusted and risk adjusted analyses were used to determine
      differences in process of care, morbidity and mortality. RESULTS: Of 89,048
      patients studied, 30,870 received their PCI at teaching hospitals and 58,178 at
      non-teaching hospitals. Risk-adjusted analysis showed no significant difference
      in death, in-hospital myocardial infarction, contrast induced nephropathy or
      gastrointestinal bleeding between teaching and non-teaching hospitals. PCI at
      teaching hospitals was associated with a lower rate of emergency coronary artery
      bypass grafting (OR, 0.63; 95% CI, 0.49-0.83; P = .0009) and an increased rate of
      vascular complications (OR, 1.33; 95% CI, 1.21-1.46; P < .0001). CONCLUSIONS:
      General outcomes of patients undergoing PCI are similar across hospital types.
      However, PCI at teaching hospitals is associated with increased risk of vascular
      complications and reduced risk of emergency coronary artery bypass grafting
      compared to non-teaching hospitals.

PMID- 24016487
TI  - The left bundle-branch block puzzle in the 2013 ST-elevation myocardial
      infarction guideline: from falsely declaring emergency to denying reperfusion in
      a high-risk population. Are the Sgarbossa Criteria ready for prime time?
AB  - Prompt and accurate identification of ST-elevation myocardial infarction (STEMI)
      in the presence of left bundle-branch block (LBBB) remains difficult. The 2004
      STEMI guideline recommended emergent reperfusion therapy to patients with
      suspected ischemia and new or presumably new LBBB. These recommendations have led
      to frequent false catheterization laboratory activation and inappropriate
      fibrinolytic therapy because most patients with suspected ischemia and new or
      presumably new LBBB do not have acute coronary artery occlusion on angiography.
      The new 2013 STEMI guideline makes a drastic change by removing previous
      recommendations. Therefore, patients with suspected ischemia and new or
      presumably new LBBB would no longer be treated as STEMI equivalent. The new
      guideline fails to recognize that some patients with suspected ischemia and LBBB
      do have STEMI, and denying reperfusion therapy could be fatal. The Sgarbossa
      electrocardiography criteria are the most validated tool to aid in the diagnosis
      of STEMI in the presence of LBBB. A Sgarbossa score of >=3 has a superb
      specificity (98%) and positive predictive value for acute myocardial infarction
      and angiography-confirmed acute coronary occlusion. Thus, we propose a diagnosis
      and triage algorithm incorporating the Sgarbossa criteria to quickly and
      accurately identify, among patients presenting with chest pain and new or
      presumably new LBBB, those with acute coronary artery occlusion. This is a high
      risk population in which reperfusion therapy would be denied by the 2013 STEMI
      guideline. Our algorithm will also significantly reduce false catheterization
      laboratory activation and inappropriate fibrinolytic therapy, the inevitable
      consequence of the 2004 STEMI guideline. 

PMID- 24016488
TI  - Overview of the 2012 Food and Drug Administration circulatory system devices
      panel meeting on the reclassification of external counterpulsation, intra-aortic
      balloon pump, and non-roller-type cardiopulmonary bypass blood pump devices.
AB  - The Food and Drug Administration held a Circulatory System Devices Advisory Panel
      meeting, December 5 and 6, 2012, to review the classification or potential
      reclassification of the following device types: external counterpulsation, intra
      aortic balloon pump (IABP), and non-roller-type cardiopulmonary bypass blood
      pumps. These 3 devices are preamendment (Medical Device Amendments of 1976) class
      III devices. The advisory panel discussed the data and provided recommendations
      for reclassification of these devices. The panel recommended reclassification of
      ECP to class II for stable angina pectoris and to retain a class III for all
      other indications. For IABP, the recommendation was to reclassify IABP to class
      II for several indications (acute coronary syndrome, cardiac and noncardiac
      surgery, and heart failure complications) and remain class III for all other
      indications. As for non-roller type, the panel recommended that for
      cardiopulmonary bypass and temporary circulatory bypass, these devices should be
      reclassified to class II while retaining a class III device status for all other
      indications, including ventricular support both for hemodynamically unstable
      patients and for prophylactic support in high-risk percutaneous interventions. 

PMID- 24016489
TI  - Embedding a randomized clinical trial into an ongoing registry infrastructure:
      unique opportunities for efficiency in design of the Study of Access site For
      Enhancement of Percutaneous Coronary Intervention for Women (SAFE-PCI for Women).
AB  - Women are at higher risk than men for bleeding and vascular complications after
      percutaneous coronary intervention (PCI). Compared with femoral access, radial
      access reduces these complications but may be more challenging in women because
      of higher rates of radial artery spasm, tortuosity, and occlusion as well as
      lower rates of procedure success. Whether the safety advantages of radial versus
      femoral access in women undergoing PCI are outweighed by reduced effectiveness
      has not been studied. The Study of Access site For Enhancement of PCI for Women
      is a prospective, randomized clinical trial comparing radial with femoral
      arterial access in women undergoing PCI. In conjunction with the US Food and Drug
      Administration's Critical Path Cardiac Safety Research Consortium, this study
      embeds the randomized clinical trial into the existing infrastructure of the
      National Cardiovascular Data Registry CathPCI Registry through the National
      Institute of Health's National Cardiovascular Research Infrastructure. The
      primary efficacy end point is a composite of bleeding (Bleeding Academic Research
      Consortium types 2, 3, or 5) or vascular complication requiring intervention
      occurring at 72 hours after PCI or by hospital discharge. The primary feasibility
      end point is procedure success. Secondary end points include procedure duration,
      contrast volume, radiation dose, quality of life, and a composite of 30-day
      death, vascular complication, or unplanned revascularization.

PMID- 24016490
TI  - Evaluation of the dual peroxisome proliferator-activated receptor alpha/gamma
      agonist aleglitazar to reduce cardiovascular events in patients with acute
      coronary syndrome and type 2 diabetes mellitus: rationale and design of the
      AleCardio trial.
AB  - BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) regulate
      transcription of genes involved in glucose uptake, lipid metabolism, and
      inflammation. Aleglitazar is a potent dual PPAR agonist with insulin-sensitizing
      and glucose-lowering actions and favorable effects on lipid profiles and
      biomarkers of cardiovascular risk. The AleCardio trial examines whether the
      addition of aleglitazar to standard medical therapy reduces the risk of
      cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus
      and recent acute coronary syndrome. STUDY DESIGN: AleCardio is a phase 3,
      multicenter, randomized, double-blind, placebo-controlled trial. A total of 7,228
      patients were randomized to aleglitazar 150 MUg or placebo daily in addition to
      standard medical therapy. The primary efficacy end point is time to the first
      event of cardiovascular death, myocardial infarction, or stroke. Principal safety
      end points are hospitalization due to heart failure and changes in renal
      function. Treatment will continue until 7,000 patients are followed up for at
      least 2.5 years and 950 primary end point events are adjudicated. CONCLUSIONS:
      AleCardio will establish whether the PPAR-alpha/gamma agonist aleglitazar
      improves cardiovascular outcomes in patients with diabetes and high-risk coronary
      disease.

PMID- 24016492
TI  - Improving outcomes in patients with atrial fibrillation: rationale and design of
      the Early treatment of Atrial fibrillation for Stroke prevention Trial.
AB  - BACKGROUND: Even on optimal therapy including anticoagulation and rate control,
      major cardiovascular complications (stroke, cardiovascular death, and acute heart
      failure) are common in patients with atrial fibrillation (AF). Conceptually,
      maintenance of sinus rhythm could prevent adverse outcomes related to AF. Rhythm
      control therapy has been only moderately effective in published trials, and its
      potential benefit was offset by side effects of repeated interventions.
      RATIONALE: Rhythm control therapy applied early after the first diagnosis of AF
      could preserve atrial structure and function and maintain sinus rhythm more
      effectively than the current practice of delayed rhythm control (when symptoms
      persist after otherwise effective rate control). Furthermore, catheter ablation
      and new antiarrhythmic drugs have enhanced the potential effectiveness and safety
      of rhythm control therapy. The EAST will test whether an early, modern rhythm
      control therapy can reduce cardiovascular complications in AF. DESIGN: The EAST
      (Early treatment of Atrial fibrillation for Stroke prevention Trial) will
      randomize approximately 3,000 patients with recent onset AF at risk for stroke
      (CHA2DS2VASc score >=2) to either guideline-mandated usual care or to usual care
      plus early rhythm control therapy in a prospective, randomized, open, blinded
      outcome assessment trial. All patients will be followed up until the end of the
      trial for the composite primary outcome of cardiovascular death, stroke,
      worsening of heart failure, and myocardial infarction. Nights spent in hospital
      will be counted as a coprimary outcome. Usual care will consist of
      anticoagulation, therapy of underlying heart disease, and rate control as an
      initial approach. Early rhythm control therapy will consist of usual care plus
      rhythm control therapy by antiarrhythmic drugs, catheter ablation, and a patient
      operated electrocardiographic device to monitor the ongoing rhythm. Key secondary
      outcomes include cognitive function and quality of life. CONCLUSION: EAST will
      determine whether rhythm control therapy, when applied early after the initial
      diagnosis of AF, can prevent cardiovascular complications associated with AF.

PMID- 24016491
TI  - Rationale and design of the Clarification of Optimal Anticoagulation through
      Genetics trial.
AB  - BACKGROUND: Current dosing practices for warfarin are empiric and result in the
      need for frequent dose changes as the international normalized ratio gets too
      high or too low. As a result, patients are put at increased risk for
      thromboembolism, bleeding, and premature discontinuation of anticoagulation
      therapy. Prior research has identified clinical and genetic factors that can
      alter warfarin dose requirements, but few randomized clinical trials have
      examined the utility of using clinical and genetic information to improve
      anticoagulation control or clinical outcomes among a large, diverse group of
      patients initiating warfarin. METHODS: The COAG trial is a multicenter, double
      blind, randomized trial comparing 2 approaches to guiding warfarin therapy
      initiation: initiation of warfarin therapy based on algorithms using clinical
      information plus an individual's genotype using genes known to influence warfarin
      response ("genotype-guided dosing") versus only clinical information ("clinical
      guided dosing") (www.clinicaltrials.gov Identifier: NCT00839657). RESULTS: The
      COAG trial design is described. The study hypothesis is that, among 1,022
      enrolled patients, genotype-guided dosing relative to clinical-guided dosing
      during the initial dosing period will increase the percentage of time that
      patients spend in the therapeutic international normalized ratio range in the
      first 4 weeks of therapy. CONCLUSION: The COAG will determine if genetic
      information provides added benefit above and beyond clinical information alone.

PMID- 24016493
TI  - The Coronary Artery Disease and Renal Failure (CAD-REF) registry: trial design,
      methods, and aims.
AB  - BACKGROUND: During the past 10 years, chronic kidney disease (CKD) has been
      recognized as a major global health problem. Factors leading to decreased renal
      function are closely related to cardiovascular disease and vice versa.
      Cardiovascular morbidity and mortality are substantially increased in patients
      with CKD, even in those with only mild or moderate renal impairment. A better
      understanding of pathogenesis, risk factors, and genetic conditions is strongly
      required for more specific treatment strategies in CKD because until now,
      knowledge is very limited. METHODS: The German CAD-REF registry is a prospective
      observational multicenter national registry. It aims at including >3,300 white
      patients with angiographically documented coronary artery disease (coronary
      artery disease [CAD]; >=50% stenosis in at least 1 coronary artery) being
      enrolled at 32 centers and assigned to 6 different groups according to their
      estimated glomerular filtration rate and/or proteinuria. Baseline
      characteristics, treatment data, and biomaterial including serum, plasma, urine,
      and DNA samples are collected. Follow-ups are performed at 6, 12, 24, 36, 48, and
      60 months. CONCLUSIONS: The CAD-REF registry will establish one of the largest
      ethnically homogeneous cohorts, to date, of clinically and angiographically well
      characterized patients with CAD who have all stages of CKD. This approach offers
      great opportunities for an improved understanding of the underlying
      pathophysiologic mechanism and clinical impact of CKD in patients with CAD,
      especially including the identification of clinically relevant risk factors and
      (genetic and other bio-) markers as a basis to ameliorate future treatment
      strategies.

PMID- 24016494
TI  - A prospective regional registry of ST-elevation myocardial infarction in Central
      Romania: impact of the Stent for Life Initiative recommendations on patient
      outcomes.
AB  - BACKGROUND: Reperfusion therapy is the treatment of choice in patients with ST
      elevation myocardial infarction (STEMI) presenting within 12 hours after the
      onset of symptoms. However, a significant number of patients do not benefit from
      it because of the lack of access to well-organized emergency care. We aimed to
      investigate the evolution of STEMI treatment and mortality between 2004 and 2011
      in an unselected population from central Romania and to demonstrate the role of a
      regional network in increasing the rates of reperfusion therapy with associated
      reduction of STEMI-related mortality in a region with very low primary
      percutaneous coronary intervention (pPCI) rates at baseline. METHODS: We analyzed
      the data of 5,899 consecutive patients with STEMI enrolled in this prospective
      study since 2004, after the initiation of an STEMI network in Central Romania and
      with continuous support of the Stent for Life Initiative. RESULTS: Introduction
      of the network was associated with an absolute change in the use of reperfusion
      therapy from 2004 to 2011 (26.94% vs 87.15%, P < .001) and of pPCI (10.88% vs
      78.64%, P < .001) for patients presenting within 12 hours after the onset of
      symptoms, with a decrease of inhospital mortality from 20.73% to 6.35% (P <
      .001). In addition, the global inhospital mortality of all the STEMI population
      showed a significant decrease (23.18% vs 13.39%, P < .001). CONCLUSIONS:
      Reduction of STEMI-related mortality was possible via implementation of pPCI,
      even in a region with low health care expenditures. The organization of an STEMI
      network led to a significant decrease in STEMI-related mortality, revealing the
      significant impact of the Stent for Life Initiative recommendations on patient
      outcomes.

PMID- 24016495
TI  - Routine early eptifibatide versus delayed provisional use at percutaneous
      coronary intervention in high-risk non-ST-segment elevation acute coronary
      syndromes patients: an analysis from the Early Glycoprotein IIb/IIIa Inhibition
      in Non-ST-Segment Elevation Acute Coronary Syndrome trial.
AB  - AIMS: In the EARLY ACS trial, routine early eptifibatide was not superior to
      delayed provisional use at percutaneous coronary intervention (PCI); however,
      among PCI-treated patients, numerically fewer ischemic end points occurred in the
      upstream eptifibatide group. We sought to further explore this finding using
      methods for examination of treatment effect in this postrandomization subgroup.
      METHODS AND RESULTS: Of 9,406 patients in the EARLY ACS primary analysis cohort,
      9,166 (97.4%) underwent coronary angiography. We used Cox proportional hazards
      regression modeling, with PCI as a time-dependent covariate, to examine the
      effect of routine early versus delayed provisional eptifibatide among 5,541
      patients undergoing PCI and to explore the interaction between treatment with PCI
      and randomized treatment strategy. After multivariable adjustment, compared with
      delayed provisional use, routine early eptifibatide was associated with lower
      rate of 30-day death or myocardial infarction (MI) after PCI (hazard ratio [HR]
      0.80, 95% CI 0.68-0.95) but not with medical management (HR 0.97, 95% CI 0.74
      1.29); PCI * randomized treatment interaction term P = .24. Excluding PCI-related
      MI, the adjusted HR for 30-day death or MI for routine early eptifibatide versus
      delayed provisional use was 0.80 (95% CI 0.60-1.08) for post-PCI treatment and
      1.01 (95% CI 0.79-1.34) for medical management; PCI * randomized treatment
      interaction term P = .28. CONCLUSIONS: Consistent with previous literature,
      upstream treatment with eptifibatide was associated with improved outcomes in
      high-risk non-ST-segment elevation acute coronary syndrome patients treated with
      PCI; however, a nonsignificant interaction term precludes a definite conclusion.

PMID- 24016496
TI  - Effect of ticagrelor on the outcomes of patients with prior coronary artery
      bypass graft surgery: insights from the PLATelet inhibition and patient outcomes
      (PLATO) trial.
AB  - BACKGROUND: Patients with prior coronary artery bypass graft surgery (CABG) who
      present with an acute coronary syndrome have a high risk for recurrent events.
      Whether intensive antiplatelet therapy with ticagrelor might be beneficial
      compared with clopidogrel is unknown. In this substudy of the PLATO trial, we
      studied the effects of randomized treatment dependent on history of CABG.
      METHODS: Patients participating in PLATO were classified according to whether
      they had undergone prior CABG. The trial's primary and secondary end points were
      compared using Cox proportional hazards regression. RESULTS: Of the 18,613 study
      patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk
      characteristics at study entry and a 2-fold increase in clinical events during
      follow-up, but less major bleeding. The primary end point (composite of
      cardiovascular death, myocardial infarction, and stroke) was reduced to a similar
      extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio
      [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77,
      0.96]; P(interaction) = .73) prior CABG. Major bleeding was similar with
      ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR,
      0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20];
      P(interaction) = .46) prior CABG. CONCLUSIONS: Prior-CABG patients presenting
      with acute coronary syndrome are a high-risk cohort for death and recurrent
      cardiovascular events but have a lower risk for major bleeding. Similar to the
      results in no-prior-CABG patients, ticagrelor was associated with a reduction in
      ischemic events without an increase in major bleeding.

PMID- 24016497
TI  - Prognostic importance of coronary anatomy and left ventricular ejection fraction
      despite optimal therapy: assessment of residual risk in the Clinical Outcomes
      Utilizing Revascularization and Aggressive DruG Evaluation Trial.
AB  - BACKGROUND: It is unknown if baseline angiographic findings can be used to
      estimate residual risk of patients with chronic stable angina treated with both
      optimal medical therapy (OMT) and protocol-assigned or symptom-driven
      percutaneous coronary intervention (PCI). METHODS: Death, myocardial infarction
      (MI), and hospitalization for non-ST-segment elevation acute coronary syndrome
      were adjudicated in 2,275 COURAGE patients. The number of vessels diseased (VD)
      was defined as the number of major coronary arteries with >=50% diameter
      stenosis. Proximal left anterior descending, either isolated or in combination
      with other disease, was also evaluated. Depressed left ventricular ejection
      fraction (LVEF) was defined as <=50%. Cox regression analyses included these
      anatomical factors as well as interaction terms for initial treatment assignment
      (OMT or OMT + PCI). RESULTS: Percutaneous coronary intervention and proximal left
      anterior descending did not influence any outcome. Death was predicted by low
      LVEF (hazard ratio [HR] 1.86, CI 1.34-2.59, P < .001) and VD (HR 1.45, CI 1.20
      1.75, P < .001). Myocardial infarction and non-ST-segment elevation acute
      coronary syndrome were predicted only by VD (HR 1.53, CI 1.30-1.81 and HR 1.24,
      CI 1.06-1.44, P = .007, respectively). CONCLUSIONS: In spite of OMT and
      irrespective of protocol-assigned or clinically driven PCI, LVEF and angiographic
      burden of disease at baseline retain prognostic power and reflect residual risk
      for secondary ischemic events.

PMID- 24016498
TI  - Race, exercise training, and outcomes in chronic heart failure: findings from
      Heart Failure - a Controlled Trial Investigating Outcomes in Exercise TraiNing
      (HF-ACTION).
AB  - BACKGROUND: The strength of race as an independent predictor of long-term
      outcomes in a contemporary chronic heart failure (HF) population and its
      association with exercise training response have not been well established. We
      aimed to investigate the association between race and outcomes and to explore
      interactions with exercise training in patients with ambulatory HF. METHODS: We
      performed an analysis of HF-ACTION, which randomized 2331 patients with HF having
      an ejection fraction <=35% to usual care with or without exercise training. We
      examined characteristics and outcomes (mortality/hospitalization, mortality, and
      cardiovascular mortality/HF hospitalization) by race using adjusted Cox models
      and explored an interaction with exercise training. RESULTS: There were 749 self
      identified black patients (33%). Blacks were younger with significantly more
      hypertension and diabetes, less ischemic etiology, and lower socioeconomic status
      versus whites. Blacks had shorter 6-minute walk distance and lower peak VO2 at
      baseline. Over a median follow-up of 2.5 years, black race was associated with
      increased risk for all outcomes except mortality. After multivariable adjustment,
      black race was associated with increased mortality/hospitalization (hazard ratio
      [HR] 1.16, 95% CI 1.01-1.33) and cardiovascular mortality/HF hospitalization (HR
      1.46, 95% CI 1.20-1.77). The hazard associated with black race was largely caused
      by increased HF hospitalization (HR 1.58, 95% CI 1.27-1.96), given similar
      cardiovascular mortality. There was no interaction between race and exercise
      training on outcomes (P > .5). CONCLUSIONS: Black race in patients with chronic
      HF was associated with increased prevalence of modifiable risk factors, lower
      exercise performance, and increased HF hospitalization, but not increased
      mortality or a differential response to exercise training.

PMID- 24016499
TI  - Implantable cardioverter-defibrillators in hypertrophic cardiomyopathy: patient
      outcomes, rate of appropriate and inappropriate interventions, and complications.
AB  - BACKGROUND: Sudden cardiac death (SCD) is the most devastating complication of
      hypertrophic cardiomyopathy (HCM), but this can be prevented by an implantable
      cardioverter-defibrillator (ICD). The aim of this study is to evaluate HCM
      patients with ICDs for primary or secondary prevention of SCD. METHODS: The study
      population consisted of all HCM patients with an ICD in 2 tertiary referral
      clinics. End points during follow-up were total and cardiac mortality,
      appropriate and inappropriate ICD intervention, and device-related complications.
      Cox-regression analysis was performed to identify predictors of outcome. RESULTS:
      ICDs were implanted in 134 patients with HCM (mean age 44 +/- 17 years, 34%
      women, 4.2 +/- 4.8 years follow-up). Annualized cardiac mortality rate was 3.4%
      per year and associated with New York Heart Association class III or IV (HR 5.2
      [2.0-14, P = .002]) and cardiac resynchronization therapy (HR 6.3 [2.1-20, P =
      .02]). Appropriate ICD interventions occurred in 38 patients (6.8%/year) and was
      associated with implantation for secondary prevention of SCD (HR 4.0 [1.8-9.1], P
      = .001) and male gender (HR 3.3 [1.2-9.0], P = .02). Inappropriate ICD
      intervention occurred in 21 patients (3.7%/year) and in 20 patients device
      related complications were documented (3.6%/year). CONCLUSION: ICDs successfully
      abort life-threatening arrhythmias in HCM patients at increased risk of SCD with
      an annualized intervention rate of 6.8% per year. End-stage heart failure is the
      main cause of mortality in these patients. The annualized rate of inappropriate
      ICD intervention was 3.7% per year, whereas device-related complications occurred
      3.6% per year.

PMID- 24016500
TI  - Association between septal strain rate and histopathology in symptomatic
      hypertrophic cardiomyopathy patients undergoing septal myectomy.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is histopathologically
      characterized by myocyte hypertrophy, disarray, interstitial fibrosis, and small
      intramural coronary arteriole dysplasia, which contribute to disease progression.
      Longitudinal systolic and early diastolic strain rate (SR) measurements by
      speckle tracking echocardiography are sensitive markers of regional myocardial
      function. We sought to determine the association between septal SR and
      histopathologic findings in symptomatic HCM patients who underwent surgical
      myectomy. METHODS: We studied 171 HCM patients (documented on histopathology) who
      underwent surgical myectomy to relieve left ventricular outflow tract
      obstruction. Various clinical and echocardiographic parameters were recorded.
      Segmental longitudinal systolic and early diastolic SRs (of the septal segment
      removed at myectomy) were measured from apical 4- and 2-chamber views (VVI 2.0;
      Siemens, Erlangen, Germany). Histopathologic myocyte hypertrophy, disarray, small
      intramural coronary arteriole dysplasia, and interstitial fibrosis were
      classified as none, mild (1%-25%), moderate (26%-50%), and severe (>50%).
      RESULTS: The mean age was 53 +/- 14 years (52% men, ejection fraction 62% +/- 5%,
      mean left ventricular outflow tract gradient 102 +/- 39 mm Hg, and basal septal
      thickness of 2.2 +/- 0.5 cm). Mean longitudinal systolic and early diastolic SRs
      were -0.91 +/- 0.5 and 0.82 +/- 0.5 (1/s), respectively. There was an inverse
      association between systolic and early diastolic septal SR and degree of myocyte
      hypertrophy, disarray, and interstitial fibrosis (all P < .05). There was no
      association between histopathologic characteristics and other echocardiography
      parameters. On multivariable regression analysis, myocyte disarray and
      echocardiographic septal hypertrophy were associated with systolic and early
      diastolic septal SR (P < .05). CONCLUSION: In HCM patients, there is inverse
      association between various histopathologic findings and septal SR. Strain rate
      might potentially provide further insight into HCM pathophysiology.

PMID- 24016501
TI  - Morbidity in children and adolescents after surgical correction of truncus
      arteriosus communis.
AB  - BACKGROUND: Studies of outcome after operative correction of truncus arteriosus
      communis (TA) have focused on mortality and rates of reintervention. We sought to
      investigate the clinical status of children and adolescents with surgically
      corrected TA. METHODS AND RESULTS: A cross-sectional study of subjects with TA
      was performed. Subjects underwent concurrent genetic testing, electrocardiogram,
      cardiac magnetic resonance imaging, cardiopulmonary exercise testing, and
      completed questionnaires assessing health status and health-related quality of
      life. Review of their medical history provided retrospective information on
      cardiac reintervention and use of medical care. Twenty-five subjects with a
      median age of 11.8 (8.1-18.99) years were enrolled. The prevalence of 22q11.2
      deletion was 32%. Incidence of hospitalization, cardiac reintervention, and
      noncardiac operations was highest in the first year of life. Combined catheter
      based and operative reintervention rates were 52% on the conduit and 56% on the
      pulmonary arteries. Right ventricular ejection fraction and end-diastolic volume
      were normal. Moderate or greater truncal valve insufficiency was seen in 11% of
      subjects, and truncal valve replacement occurred in 8% of subjects. Maximal
      oxygen consumption (P = .0002), maximal work (P < .0001), and forced vital
      capacity (P < .0001) were all lower than normal for age and sex. Physical health
      status and health-related quality of life were both severely diminished.
      CONCLUSION: Patients with TA demonstrate significant comorbid disease throughout
      childhood, significant burden of operative and catheter-based reintervention, and
      deficits in exercise performance, functional status, and health-related quality
      of life.

PMID- 24016502
TI  - Change in enrollment patterns, patient selection, and clinical outcomes with the
      availability of drug-eluting stents in the Bypass Angioplasty Revascularization
      Investigation 2 Diabetes trial.
AB  - BACKGROUND: In the BARI 2D trial, patients with type 2 diabetes and stable
      coronary artery disease were randomized to prompt revascularization versus
      intensive medical therapy (IMT). This analysis sought to evaluate how the
      availability of drug-eluting stents (DESs) has changed practice and outcomes.
      METHODS: In BARI 2D, 1,605 patients were in the percutaneous coronary
      intervention (PCI)-intended stratum. As DES became available midway through
      recruitment, we report clinical outcomes among patients who underwent IMT versus
      prompt PCI with bare-metal stents (BMSs) or DES up to 4 years. RESULTS: In North
      America, after DES became available, selection for the PCI-intended stratum
      increased from 73% to 79% (P = .003). Fewer BMS than DES patients had total
      occlusions treated or underwent rotational atherectomy (5.6% vs 9.7%, P = .02,
      and 1.2% vs 3.7%, P < .01, respectively). Subsequent revascularization (IMT 39%,
      BMS 29%, DES 21%, P < .01) and target vessel revascularization (BMS 16.1% vs DES
      9.6%, P = .03) were lower with DES. Angina at 2 years tended to be less common
      with DES (IMT 39%, BMS 37%, DES 29%, P = .04, for 3 groups, P = .07 for DES vs
      BMS). The composite of death, myocardial infarction, or stroke was IMT 16.0%, BMS
      20.5%, DES 17.5%; P = .80. CONCLUSIONS: When DES became available in North
      America, patients were more likely to be selected into the PCI-intended stratum.
      Compared with patients receiving BMS, those receiving DES tended to have less
      target vessel revascularization and angina.

PMID- 24016503
TI  - A multicenter randomized comparison of paclitaxel-coated balloon catheter with
      conventional balloon angioplasty in patients with bare-metal stent restenosis and
      drug-eluting stent restenosis.
AB  - BACKGROUND: The aim of this study was to investigate the efficacy and safety of
      paclitaxel-coated balloon (PCB) for the treatment of the bare-metal stent
      restenosis (BMS-ISR) and drug-eluting stent restenosis (DES-ISR). METHODS: This
      study was a prospective, multicenter, randomized (2:1) trial conducted in 208
      patients with 213 in-stent restenosis lesions (BMS-ISR: 123 lesions, DES-ISR: 90
      lesions) at 13 centers in Japan. Patients were randomly assigned to a PCB group
      (137 patients with 142 lesions) or a conventional balloon angioplasty (BA) group
      (71 patients with 71 lesions). The primary end point was target vessel failure at
      6-month follow-up. RESULTS: Clinical and angiographic follow-up 6 months after
      intervention was performed in 207 patients (99.5%) with 208 lesions (97.7%).
      Target vessel failure was noted in 6.6% of the PCB group and 31.0% of the BA
      group (P < .001). Recurrent restenosis occurred in 4.3% of the PCB group and
      31.9% of the BA group (P < .001). Late lumen loss was lower in the PCB group than
      in the BA group (0.11 +/- 0.33 mm vs 0.49 +/- 0.50 mm, P < .001). In PCB-treated
      lesions, recurrent restenosis occurred in 1.1% of patients with BMS-ISR and in
      9.1% of patients with DES-ISR (P = .04). Late lumen loss was lower in patients
      with BMS-ISR than in patients with DES-ISR (0.05 +/- 0.28 mm vs 0.18 +/- 0.38 mm,
      P = .03). CONCLUSIONS: This randomized clinical study suggested that PCB provided
      much better clinical and angiographic outcomes than did conventional BA in
      patients with BMS-ISR and DES-ISR. Drug-eluting stent restenosis was associated
      with poorer outcomes compared with BMS-ISR after treatment with PCB.

PMID- 24016504
TI  - Bleeding after percutaneous coronary intervention in women and men matched for
      age, body mass index, and type of antithrombotic therapy.
AB  - BACKGROUND: Factors underlying the increased risk of bleeding after percutaneous
      coronary intervention (PCI) in women compared with men remain incompletely
      understood. METHODS: The study included 3,351 women and 3,351 men matched for
      age, body mass index, and type of antithrombotic therapy. Bleeding within the 30
      days after PCI was defined using the Bleeding Academic Research Consortium
      criteria. The main outcome was 1-year mortality. RESULTS: Bleeding occurred in
      518 women and 354 men (15.5% vs 10.6%, odds ratio [OR] 1.55, 95% CI 1.34-1.79, P
      < .001). Severe (Bleeding Academic Research Consortium class >=2) bleeds (9.4% vs
      6.5%, P < .001) and access site bleeds (10.1% vs 5.4%, P < .001) were more common
      in women. After adjustment, female sex remained an independent correlate of any
      bleeding (adjusted OR 1.61 [1.35-1.92], P < .001) and access site (adjusted OR
      2.00 [1.59-2.50], P < .001) but not of nonaccess site (adjusted OR 1.18 [0.91
      1.54], P = .205) bleeding. There were 248 deaths: 32 deaths among men with
      bleeding versus 107 deaths among men with no bleeding (9.1% vs 3.6%, OR 2.68
      [1.78-4.05], P < .001) and 40 deaths among women with bleeding vs 69 deaths among
      women with no bleeding (7.8% vs 2.5%, OR 3.35 [2.24-5.01], P < .001). No
      difference in mortality was observed among women and men who bled (P = .487).
      Bleeding was independently associated 1-year mortality (adjusted hazard ratio
      2.18 [1.68-2.84], P < .001) with no bleeding-by-sex interaction (P = .439).
      CONCLUSIONS: Despite matching for age, body mass index, and type of
      antithrombotic therapy, bleeding risk after PCI remained significantly higher in
      women than in men. Bleeding was associated with increased risk of 1-year
      mortality with no bleeding-by-sex interaction.

PMID- 24016505
TI  - High-sensitive cardiac troponin T and its relations to cardiovascular risk
      factors, morbidity, and mortality in elderly men.
AB  - BACKGROUND: Cardiac troponin is emerging as risk indicator in community-dwelling
      populations. In this study, we investigated the associations of cardiac troponin
      T (cTnT) to cardiovascular (CV) disease and outcome in elderly men. METHODS:
      Cardiac troponin T was measured using a high-sensitive assay in 940 men aged 71
      years participating in the Uppsala Longitudinal Study of Adult Men. We assessed
      both the cross-sectional associations of cTnT to CV risk factors and morbidities
      including cancer and the longitudinal associations to outcomes over 10 years of
      follow-up. RESULTS: Cardiac troponin T levels were measurable in 872 subjects
      (92.8%). In the cross-sectional analyses, cTnT was associated to CV risk factors
      (diabetes, smoking, and obesity), renal dysfunction, CV disease including atrial
      fibrillation and coronary artery disease, and biomarkers of inflammation and left
      ventricular dysfunction. In the longitudinal analyses, cTnT independently
      predicted total mortality and CV events including stroke. The standardized
      adjusted hazard ratio regarding the composite CV end point was 1.5 (95% CI 1.3
      1.8), P < .001, for men with prevalent CV disease and 1.2 (95% CI 1.0-1.4), P =
      .02, for men without. Cardiac troponin T improved discrimination metrics for all
      outcomes in the total population. This was mainly driven by the prognostic value
      of cTnT in subjects with prevalent CV disease. CONCLUSIONS: In community-dwelling
      men, cTnT levels are associated to CV risk factors and morbidities and predict
      both fatal and nonfatal CV events. The relations to outcome are mainly seen in
      men with prevalent CV disease indicating that the prognostic value of cTnT in
      subjects free from CV disease is limited.

PMID- 24016506
TI  - Apixaban versus warfarin in patients with atrial fibrillation according to prior
      warfarin use: results from the Apixaban for Reduction in Stroke and Other
      Thromboembolic Events in Atrial Fibrillation trial.
AB  - BACKGROUND: Patients with atrial fibrillation who are vitamin K antagonist (VKA)
      naive may have a higher risk of thrombosis and/or bleeding than VKA-experienced
      patients. METHODS AND RESULTS: Using data from ARISTOTLE, we assessed baseline
      characteristics and the treatment effect of apixaban versus warfarin in the VKA
      naive and VKA-experienced cohorts. We compared rates of study drug
      discontinuation and time-in-therapeutic range. Overall, 7,800 (43%) were VKA
      naive, and 10,401 were VKA experienced. At baseline, both groups were similar
      with respect to age and congestive heart failure, hypertension, age, diabetes,
      stroke score (CHADS2). Fewer VKA-naive patients had a history of prior stroke
      (18% vs 21%) or prior bleeding (10% vs 22%) and were more often female (39% vs
      33%). The effect of apixaban on the primary efficacy and safety outcomes was
      similar in VKA-naive (stroke/systemic embolism: hazard ratio [HR] 0.86, 95% CI
      0.67-1.11 and major bleeding: HR 0.73, 95% CI 0.59-0.91) and VKA-experienced
      populations (stroke/systemic embolism: HR 0.73, 95% CI 0.57-0.95, P value for
      interaction = 0.39 and major bleeding: HR 0.66, 95% CI 0.55-0.80, P value for
      interaction = 0.50). Permanent study drug discontinuation was numerically less
      likely in patients receiving apixaban whether they were VKA naive (HR for
      discontinuation: 0.87, 95% CI 0.79-0.95) or VKA experienced (HR for
      discontinuation: 0.93, 95% CI 0.85-1.02). Among patients receiving warfarin, the
      mean/median times in therapeutic range were lower in the VKA-naive group (VKA
      naive: 57.5/61.4, VKA-experienced: 66.0/69.1, P < .001). CONCLUSION: The
      treatment effects of apixaban (vs warfarin) were not modified by VKA naivety. The
      rates of stroke/systemic embolism and major bleeding were numerically lower among
      the patients assigned to apixaban, irrespective of prior VKA use.

PMID- 24016507
TI  - Documentation of study medication dispensing in a prospective large randomized
      clinical trial: experiences from the ARISTOTLE Trial.
AB  - BACKGROUND: In ARISTOTLE, apixaban resulted in a 21% reduction in stroke, a 31%
      reduction in major bleeding, and an 11% reduction in death. However, approval of
      apixaban was delayed to investigate a statement in the clinical study report that
      "7.3% of subjects in the apixaban group and 1.2% of subjects in the warfarin
      group received, at some point during the study, a container of the wrong type."
      METHODS: Rates of study medication dispensing error were characterized through
      reviews of study medication container tear-off labels in 6,520 participants from
      randomly selected study sites. The potential effect of dispensing errors on study
      outcomes was statistically simulated in sensitivity analyses in the overall
      population. RESULTS: The rate of medication dispensing error resulting in
      treatment error was 0.04%. Rates of participants receiving at least 1 incorrect
      container were 1.04% (34/3,273) in the apixaban group and 0.77% (25/3,247) in the
      warfarin group. Most of the originally reported errors were data entry errors in
      which the correct medication container was dispensed but the wrong container
      number was entered into the case report form. Sensitivity simulations in the
      overall trial population showed no meaningful effect of medication dispensing
      error on the main efficacy and safety outcomes. CONCLUSIONS: Rates of medication
      dispensing error were low and balanced between treatment groups. The initially
      reported dispensing error rate was the result of data recording and data
      management errors and not true medication dispensing errors. These analyses
      confirm the previously reported results of ARISTOTLE.

PMID- 24016508
TI  - African American race but not genome-wide ancestry is negatively associated with
      atrial fibrillation among postmenopausal women in the Women's Health Initiative.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in women and
      is associated with higher rates of stroke and death. Rates of AF are lower in
      African American subjects compared with European Americans, suggesting European
      ancestry could contribute to AF risk. METHODS: The Women's Health Initiative
      (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for
      various cardiovascular outcomes including AF. Multivariate Cox hazard regression
      analysis was used to measure the association between African American race and
      incident AF. A total of 8,119 African American women from the WHI randomized
      clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0.
      Genome-wide ancestry and previously reported single nucleotide polymorphisms
      associated with AF in European cohorts were tested for association with AF using
      multivariate logistic regression analyses. RESULTS: Self-reported African
      American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI
      0.32-0.60) in the OS, independent of demographic and clinical risk factors. In
      the genotyped cohort, there were 558 women with AF. By contrast, genome-wide
      European ancestry was not associated with AF. None of the single nucleotide
      polymorphisms previously associated with AF in European populations, including
      rs2200733, were associated with AF in the WHI African American cohort.
      CONCLUSION: African American race is significantly and inversely correlated with
      AF in postmenopausal women. The etiology of this association remains unclear and
      may be related to unidentified environmental differences. Larger studies are
      necessary to identify genetic determinants of AF in African Americans.

PMID- 24016509
TI  - Burden, timing, and relationship of cardiovascular hospitalization to mortality
      among Medicare beneficiaries with newly diagnosed atrial fibrillation.
AB  - BACKGROUND: Limited data exist on the burden and relationship of cardiovascular
      (CV) hospitalization to mortality after newly diagnosed with atrial fibrillation
      (AF). METHODS: Using a 20% sample of nationwide Medicare Part A and B claims
      data, we performed a retrospective cohort study of Medicare beneficiaries with
      newly diagnosed AF (2004-2008). Cox proportional hazards time-varying exposures
      were used to determine the risk of death among patients with CV hospitalization
      after AF diagnosis. RESULTS: Of 228,295 patients (mean age 79.6 +/- 7.4 years,
      56% female), 57% had a CV hospitalization after diagnosis of AF (41% in the first
      year). The most common primary CV hospitalization diagnoses were
      AF/supraventricular arrhythmias (21%), heart failure (19%), myocardial infarction
      (11%), and stroke/transient ischemic attack (7.7%). Incidence rates per 1,000
      person-years among patients with and without CV hospitalization were 114 and 87,
      respectively, for all-cause mortality. After adjustment for covariates and time
      to CV hospitalization, the hazard of mortality among newly diagnosed AF patients
      with CV hospitalization, compared with those without CV hospitalization, was
      higher (hazard ratio 1.22, 95% CI 1.20-1.24). CONCLUSIONS: Cardiovascular
      hospitalization is common in the first year after AF diagnosis. Atrial
      fibrillation, heart failure, myocardial infarction, and stroke/transient ischemic
      attack account for half of primary hospitalization diagnosis. Cardiovascular
      hospitalization is independently associated with mortality, irrespective of time
      from diagnosis to first hospitalization, and represents a critical inflection
      point in survival trajectory. These findings highlight the importance of CV
      hospitalization as a marker of disease progression and poor outcomes. Efforts to
      clarify the determinants of hospitalization could inform interventions to reduce
      admissions and improve survival.

PMID- 24016510
TI  - Appropriate test selection for single-photon emission computed tomography
      imaging: association with clinical risk, posttest management, and outcomes.
AB  - BACKGROUND: Appropriate use criteria (AUC) for stress single-photon emission
      computed tomography (SPECT) are only one step in appropriate use of imaging.
      Other steps include pretest clinical risk evaluation and optimal management
      responses. We sought to understand the link between AUC, risk evaluation,
      management, and outcome. METHODS: We used AUC to classify 1,199 consecutive
      patients (63.8 +/- 12.5 years, 56% male) undergoing SPECT as inappropriate,
      uncertain, and appropriate. Framingham score for asymptomatic patients and
      Bethesda angina score for symptomatic patients were used to classify patients
      into high (>=5%/y), intermediate, and low (<=1%/y) risk. Subsequent patient
      management was defined as appropriate or inappropriate based on the concordance
      between management decisions and the SPECT result. Patients were followed up for
      a median of 4.8 years, and cause of death was obtained from the social security
      death registry. RESULTS: Overall, 62% of SPECTs were appropriate, 18%
      inappropriate, and 20% uncertain (only 5 were unclassified). Of 324 low-risk
      studies, 108 (33%) were inappropriate, compared with 94 (15%) of 621 intermediate
      risk and 1 (1%) of 160 high-risk studies (P < .001). There were 79 events, with
      outcomes of inappropriate patients better than uncertain and appropriate
      patients. Management was appropriate in 986 (89%), and appropriateness of patient
      management was unrelated to AUC (P = .65). CONCLUSION: Pretest clinical risk
      evaluation may be helpful in appropriateness assessment because very few high
      risk patients are inappropriate, but almost half of low-risk patients are
      inappropriate or uncertain. Appropriate patient management is independent of
      appropriateness of testing.

PMID- 24016511
TI  - Predictors of discordance between physicians' and patients' appraisals of health
      related quality of life in atrial fibrillation patients: findings from the
      Angiotensin II Antagonist in Paroxysmal Atrial Fibrillation Trial.
AB  - BACKGROUND: Assessing health status is fundamental when weighing treatment
      options for atrial fibrillation (AF) patients. Most health-related quality-of
      life (HRQoL) data stem from self-ratings, whereas treatment decisions are based
      upon physicians' estimations. METHODS: The degree of congruence between patients'
      and physicians' assessments of the patients' subjective health status was used as
      an indicator of good communication and shared understanding. A total of 334
      patients with paroxysmal AF without significant concomitant heart diseases and
      their physicians were asked in a prospective blinded study to rate the patients'
      HRQoL. The Short Form-12 was used for self-ratings; the Short Form-8, for
      physician ratings. Using baseline data, intraclass correlations and Bland-Altman
      graphs were used to assess concordance; cross-sectional multivariate regression
      analyses assessed patient characteristics associated with discordance. RESULTS:
      On average, physicians rated their patients' HRQoL higher than patients did
      (?mental component score [MCS] = -3.23, P < .0001, and ?physical component score
      [PCS] = -2.21, P = .0001). Intraclass correlations and Bland-Altman graphs showed
      unsatisfactory concordance. Physical inactivity (? = 4.84) had the greatest
      bivariate effect on PCS discordance, and major depressive disorder (? = 7.01), on
      MCS discordance. In the regression analyses, depression was significantly
      associated with discord in the MCS (beta = -0.94, P < .001) and the PCS (beta = 
      0.37, P < .002). Sleeping disorder was associated with discord in the MCS (beta =
      -4.13, P < .002), and physical inactivity, with discord in the PCS (beta = -1.47,
      P = .006). CONCLUSIONS: In patients with AF, even in the absence of significant
      concomitant cardiac diseases, depression, followed by sleeping disorder and
      physical inactivity, was significantly associated with discordance. These
      findings should be considered by physicians when choosing treatment strategies.

PMID- 24016513
TI  - Response to Letter to the Editor by Blankfield regarding "Assessment of drug
      induced increases in blood pressure during drug development: report from the
      Cardiac Safety Research Consortium.".

PMID- 24016512
TI  - Treatment strategies in patients with statin intolerance: the Cleveland Clinic
      experience.
AB  - BACKGROUND: Statin therapy is a proven effective treatment of hyperlipidemia.
      However, a significant number of patients cannot tolerate statins. This study was
      conducted to review treatment strategies for patients intolerant to statin
      therapy with a focus on intermittent statin dosing. METHODS AND RESULTS: We
      performed a retrospective analysis of medical records of 1,605 patients referred
      to the Cleveland Clinic Preventive Cardiology Section for statin intolerance
      between January 1995 and March 2010 with at least a 6-month follow-up. The
      changes in lipid profile, achievement of low-density lipoprotein cholesterol (LDL
      C) goals, and statin tolerance rate were analyzed. Most (72.5%) of patients with
      prior statin intolerance were able to tolerate a statin for the median follow-up
      time of 31 months. Patients on intermittent statin dosing (n = 149) had
      significantly lower LDL-C reduction compared with daily dosing group (n = 1,014;
      21.3% +/- 4.0% vs 27.7% +/- 1.4%, P < .04). However, compared with the statin
      discontinued group (n = 442), they had a significantly higher LDL-C reduction
      (21.3% +/- 4.0% vs 8.3 +/- 2.2%, P < .001), and a significantly higher portion
      achieved their Adult Treatment Panel III goal of LDL-C (61% vs 44%, P < .05).
      There was a trend toward a decrease in all-cause mortality at 8 years for
      patients on daily and intermittent statin dosing compared with those who
      discontinued statin (P = .08). CONCLUSIONS: Most patients with previous statin
      intolerance can tolerate subsequent trial of statin. A strategy of intermittent
      statin dosing can be an effective therapeutic option in some patients and may
      result in reduction in LDL-C and achievement of LDL-C goals.

PMID- 24016514
TI  - Exercise-induced pulmonary hypertension in systemic sclerosis: a multifactorial
      entity.

PMID- 24016515
TI  - Response to letter to the editor by Rui Baptista, M.D., Rogerio Teixeira, M.D.

PMID- 24016516
TI  - The need to know crude event rates in meta-analysis.

PMID- 24016517
TI  - Response to letter by Messeri et al.

PMID- 24016518
TI  - Renal dysfunction may predict new onset heart failure.

PMID- 24016519
TI  - Response to letter by Balta et al regarding "Renal dysfunction and long-term risk
      of heart failure after coronary artery bypass grafting".

PMID- 24016520
TI  - Letter to the Editor regarding "Assessment of drug-induced increases in blood
      pressure during drug development: report from the Cardiac Safety Research
      Consortium".

PMID- 24016521
TI  - Healthy Alberta Communities: impact of a three-year community-based obesity and
      chronic disease prevention intervention.
AB  - OBJECTIVE: To assess the impact of a 3 year (2006-2009) community-based
      intervention for obesity and chronic disease prevention in four diverse "Healthy
      Alberta Communities" (HAC). METHODS: Targeted intervention development
      incorporated the ANGELO conceptual framework to help community stakeholders
      identify environmental determinants of obesity amenable to intervention. Several
      inter-related initiatives were implemented. To evaluate, we surveyed separate
      samples of adults in HAC communities before and after the interventions and
      compared responses to identical survey questions asked of adults living in
      Alberta in two waves of the Canadian Community Health Survey (CCHS). RESULTS: The
      HAC sample included 4761 (2006) and 4733 (2009) people. The comparison sample
      included 9775 and 9784 respondents in 2005 and 2009-10 respectively. Self
      reported body mass index showed no change, and neither were there significant
      changes in behaviors relative to secular trends. Most significant outcomes were
      relevant to social conditions, specifically sense of belonging to community in
      the intervention communities. CONCLUSION: Health outcome indicators at the
      community level may not be sufficiently sensitive to capture changes which, over
      a relatively short term, would only be expected to be incremental, given that
      interventions were directed primarily to creating environmental conditions
      supportive of changes in behavioral outcomes rather than toward health outcome
      change directly.

PMID- 24016522
TI  - Cell and molecular biology of DNA methyltransferase 1.
AB  - The DNA cytosine methyltransferase 1 (DNMT1) is a ubiquitous nuclear enzyme that
      catalyzes the well-established reaction of placing methyl groups on the
      unmethylated cytosines in methyl-CpG:CpG base pairs in the hemimethylated DNA
      formed by methylated parent and unmethylated daughter strands. This activity
      regenerates fully methylated methyl-CpG:methyl-CpG pairs. Despite the
      straightforward nature of its catalytic activity, detailed biochemical, genetic,
      and developmental studies revealed intricate details of the central regulatory
      role of DNMT1 in governing the epigenetic makeup of the nuclear genome. DNMT1
      mediates demethylation and also participates in seemingly wide cellular functions
      unrelated to maintenance DNA methylation. This review brings together mechanistic
      details of maintenance methylation by DNMT1, its regulation at transcriptional
      and posttranscriptional levels, and the seemingly unexpected functions of DNMT1
      in the context of DNA methylation which is central to epigenetic changes that
      occur during development and the process of cell differentiation. 

PMID- 24016523
TI  - Endothelial progenitor cells--potential new avenues to improve neoangiogenesis
      and reendothelialization.
AB  - The term endothelial progenitor cell (EPC) was established more than 10 years ago
      and is used to refer to a group of circulating cells that display endothelial
      lineage qualities and are able to home to areas of ischemia or vascular injury
      and to facilitate the repair of damaged blood vessels or develop new vessels as
      needed. This chapter reviews the current lineage relationships among all the
      cells called EPC and will clear the terminology used in EPC research.
      Furthermore, an overview of the clinical and in vitro research, as well as
      cytokine and drug interactions and potential EPC applications, is given. 

PMID- 24016524
TI  - Interplay between spindle architecture and function.
AB  - The mitotic spindle performs the universal and crucial function of segregating
      chromosomes to daughter cells, and all spindles share common characteristics that
      facilitate this task. The spindle is built from microtubule (MT) polymers and
      hundreds of associated factors that assemble into a dynamic steady-state
      structure that is tuned to the cellular environment. In this review, we discuss
      the phenomenology and underlying mechanisms that describe how spindle
      architecture is optimized to promote robust chromosome segregation in diverse
      cell types. We focus on the role of MT dynamics, stabilization, and transport in
      an effort to understand how the molecular mechanisms governing these processes
      lead to the formation of the functional, steady-state spindle structure. Finally,
      we investigate the basis of spindle variation and discuss why spindles take on
      certain forms in different cell types. The recent advances in understanding
      spindle biology have shown that spindle assembly utilizes multiple but common
      pathways weighted differently in different cells and organisms. These assembly
      differences are correlated with variations in spindle architectures that may
      influence the regulation of molecules in the spindle. Overall, as architectural
      features of different spindles are elucidated, the available comparative genomic
      data should provide structural and mechanistic insight into how a spindle is
      built, how dynamic interactions lead to a steady-state structure, and how spindle
      function is disrupted in disease. 

PMID- 24016525
TI  - Regulation of cell polarity and RNA localization in vertebrate oocytes.
AB  - It has long been appreciated that the inheritance of maternal cytoplasmic
      determinants from different regions of the egg can lead to differential
      specification of blastomeres during cleavage. Localized RNAs are important
      determinants of cell fate in eggs and embryos but are also recognized as
      fundamental regulators of cell structure and function. This chapter summarizes
      recent molecular and genetic experiments regarding: (1) mechanisms that regulate
      polarity during different stages of vertebrate oogenesis, (2) pathways that
      localize presumptive protein and RNA determinants within the polarized oocyte and
      egg, and (3) how these determinants act in the embryo to determine the ultimate
      cell fates. Emphasis is placed on studies done in Xenopus, where extensive work
      has been done in these areas, and comparisons are drawn with fish and mammals.
      The prospects for future work using in vivo genome manipulation and other
      postgenomic approaches are also discussed. 

PMID- 24016526
TI  - Insights into the role of cell-cell junctions in physiology and disease.
AB  - Contacting cells establish different classes of intricate structures at the cell
      cell junctions. These structures are of increasing research interest as they
      regulate a broad variety of processes in development and disease. Further, in
      vitro studies are revealing that various cell-cell interaction proteins are
      involved not only in cell-cell processes but also in many additional aspects of
      physiology, such as migration and apoptosis. This chapter reviews the basic
      classification of cell-cell junctional structures and some of their
      representative proteins. Their roles in development and disease are briefly
      outlined, followed by a section on contemporary methods for probing cell-cell
      interactions and some recent developments. This chapter concludes with a few
      suggestions for potential research directions to further develop this promising
      area of study. 

PMID- 24016527
TI  - New insights into the role of BubR1 in mitosis and beyond.
AB  - BubR1 is a critical component of the spindle assembly checkpoint, the
      surveillance mechanism that helps maintain the high fidelity of mitotic
      chromosome segregation by preventing cells from initiating anaphase if one or
      more kinetochores are not attached to the spindle. BubR1 also helps promote the
      establishment of stable kinetochore-microtubule attachments during prometaphase.
      In this chapter, we review the structure, functions, and regulation of BubR1 in
      these "classical roles" at the kinetochore. We discuss its recruitment to
      kinetochores, its assembly into the inhibitor of anaphase progression, and the
      importance of its posttranslational modifications. We also consider the evidence
      for its participation in other roles beyond mitosis, such as the meiosis-specific
      processes of recombination and prophase arrest of the first meiotic division, the
      cellular response to DNA damage, and in the regulation of centrosome and basal
      body function. Finally, studies are presented linking BubR1 dysfunction or
      misregulation to aging and human disease, particularly cancer. 

PMID- 24016528
TI  - Automated methods for the analysis of skeletal muscle fiber size and metabolic
      type.
AB  - It is of interest to quantify the size, shape, and metabolic subtype of skeletal
      muscle fibers in many areas of biomedical research. To do so, skeletal muscle
      samples are sectioned transversely to the length of the muscle and labeled for
      extracellular or membrane proteins to delineate the fiber boundaries and
      additionally for biomarkers related to function or metabolism. The samples are
      digitally photographed and the fibers "outlined" for quantification of fiber
      cross-sectional area (CSA) using pointing devices interfaced to a computer, which
      is tedious, prone to error, and can be nonobjective. Here, we review methods for
      characterizing skeletal muscle fibers and describe new automated techniques,
      which rapidly quantify CSA and biomarkers. We discuss the applications of these
      methods to the characterization of mitochondrial dysfunctions, which underlie a
      variety of human afflictions, and we present a novel approach, utilizing images
      from the online Human Protein Atlas to predict relationships between fiber
      specific protein expression, function, and metabolism. 

PMID- 24016529
TI  - Cell biology of chromerids: autotrophic relatives to apicomplexan parasites.
AB  - Chromerida are algae possessing a complex plastid surrounded by four membranes.
      Although isolated originally from stony corals in Australia, they seem to be
      globally distributed. According to their molecular phylogeny, morphology,
      ultrastructure, structure of organellar genomes, and noncanonical pathway for
      tetrapyrrole synthesis, these algae are thought to be the closest known
      phototrophic relatives to apicomplexan parasites. Here, we summarize the current
      knowledge of cell biology and evolution of this novel group of algae, which
      contains only two formally described species, but is apparently highly diverse
      and virtually ubiquitous in marine environments. 

PMID- 24016530
TI  - Contractile vacuole complex--its expanding protein inventory.
AB  - The contractile vacuole complex (CVC) of some protists serves for the osmotic
      equilibration of water and ions, notably Ca(2+), by chemiosmotic exploitation of
      a H(+) gradient generated by the organelle-resident V-type H(+)-ATPase. Ca(2+) is
      mostly extruded, but there is also some reflux into the cytosol via Ca(2+)
      release channels. Most data available are from Dictyostelium and Paramecium. In
      Paramecium, the major parts of CVC contain several v-/R-SNARE (synaptobrevins)
      and t-/Q-SNARE (syntaxins) proteins. This is complemented by Rab-type GTPases
      (shown in Tetrahymena) and exocyst components (Chlamydomonas). All this reflects
      a multitude of membrane interactions and fusion processes. Ca(2+)/H(+) and other
      exchangers are to be postulated, as are aquaporins and mechanosensitive Ca(2+)
      channels. From the complexity of the organelle, many more proteins may be
      expected. For instance, the pore is endowed with its own set of proteins. We may
      now envisage the regulation of membrane dynamics (reversible tubulation) and the
      epigenetic control of organelle shape, size and positioning. New aspects about
      organelle function and biogenesis are sketched in Section 7. The manifold
      regulators currently known from CVC suggest the cooperation of widely different
      mechanisms to maintain its dynamic function and to drive its biogenesis. 

PMID- 24016531
TI  - Poststimulus response characteristics of the human cone flicker
      electroretinogram.
AB  - At certain temporal frequencies, the human cone flicker electroretinogram (ERG)
      contains multiple additional responses following the termination of a flicker
      train. The purpose of this study was to determine whether these poststimulus
      responses are a continuing response to the terminated flicker train or represent
      the oscillation of a resonant system. ERGs were recorded from 10 visually normal
      adults in response to full-field sinusoidally modulated flicker trains presented
      against a short-wavelength rod-saturating adapting field. The amplitude and
      timing properties of the poststimulus responses were evaluated within the context
      of a model of a second-order resonant system. At stimulus frequencies between
      41.7 and 71.4 Hz, the majority of subjects showed at least three additional ERG
      responses following the termination of the flicker train. The interval between
      the poststimulus responses was approximately constant across stimulus frequency,
      with a mean of 14.4 ms, corresponding to a frequency of 69.4 Hz. The amplitude
      and timing characteristics of the poststimulus ERG responses were well described
      by an underdamped second-order system with a resonance frequency of 70.3 Hz. The
      observed poststimulus ERG responses may represent resonant oscillations of
      retinal ON bipolar cells, as has been proposed for electrophysiological
      recordings of poststimulus responses from retinal ganglion cells. However,
      further investigation is required to determine the types of retinal neurons
      involved in the generation of the poststimulus responses of the human flicker
      ERG.

PMID- 24016534
TI  - Reproductive health laws and fertility decline in Ghana.
AB  - BACKGROUND: An unresolved debate in demography concerns the causal sequence
      between the supply of contraception and the demand for smaller families in
      fertility decline. Through a mixed-methods approach, we explored the effect of a
      sudden increase in access to legal abortion on subsequent fertility decline when
      Ghana's criminal code was amended in 1985. METHODS: Using Ghana Demographic and
      Health Surveys, we constructed a panel of women aged 15-34 years and undertook a
      spline regression analysis to examine the effect of legal changes in 1985 and
      fertility decline controlling for social determinants of fertility. In addition,
      we conducted 17 key informant interviews (KIIs) to understand the reasons for the
      legal change and competing explanations for fertility decline. RESULTS:
      Multivariate results indicated that the timing of the liberalization of the
      abortion law coincided with the onset of Ghana's fertility decline. The KIIs
      indicated that the reasons for the liberalization of reproductive health laws
      were in response to famine and physician advocacy. CONCLUSIONS: While the timing
      of the abortion law liberalization coincided with the fertility decline in Ghana,
      we are unable to decouple the effect of the legal change from the effects of a
      severe famine that affected the region at the same time. Further research on
      documented and undocumented abortion in Ghana should be conducted to validate the
      contribution of legal abortion to fertility decline.

PMID- 24016533
TI  - Isolation of deer tick virus (Powassan virus, lineage II) from Ixodes scapularis
      and detection of antibody in vertebrate hosts sampled in the Hudson Valley, New
      York State.
AB  - BACKGROUND: Deer tick virus, DTV, is a genetically and ecologically distinct
      lineage of Powassan virus (POWV) also known as lineage II POWV. Human incidence
      of POW encephalitis has increased in the last 15 years potentially due to the
      emergence of DTV, particularly in the Hudson Valley of New York State. We
      initiated an extensive sampling campaign to determine whether POWV was extant
      throughout the Hudson Valley in tick vectors and/or vertebrate hosts. METHODS:
      More than 13,000 ticks were collected from hosts or vegetation and tested for the
      presence of DTV using molecular and virus isolation techniques. Vertebrate hosts
      of Ixodes scapularis (black-legged tick) were trapped (mammals) or netted (birds)
      and blood samples analyzed for the presence of neutralizing antibodies to POWV.
      Maximum likelihood estimates (MLE) were calculated to determine infection rates
      in ticks at each study site. RESULTS: Evidence of DTV was identified each year
      from 2007 to 2012, in nymphal and adult I. scapularis collected from the Hudson
      Valley. 58 tick pools were positive for virus and/or RNA. Infection rates were
      higher in adult ticks collected from areas east of the Hudson River. MLE limits
      ranged from 0.2-6.0 infected adults per 100 at sites where DTV was detected.
      Virginia opossums, striped skunks and raccoons were the source of infected
      nymphal ticks collected as replete larvae. Serologic evidence of POWV infection
      was detected in woodchucks (4/6), an opossum (1/6), and birds (4/727). Lineage I,
      prototype POWV, was not detected. CONCLUSIONS: These data demonstrate widespread
      enzootic transmission of DTV throughout the Hudson Valley, in particular areas
      east of the river. High infection rates were detected in counties where recent
      POW encephalitis cases have been identified, supporting the hypothesis that
      lineage II POWV, DTV, is responsible for these human infections.

PMID- 24016532
TI  - Retinal connectomics: towards complete, accurate networks.
AB  - Connectomics is a strategy for mapping complex neural networks based on high
      speed automated electron optical imaging, computational assembly of neural data
      volumes, web-based navigational tools to explore 10(12)-10(15) byte (terabyte to
      petabyte) image volumes, and annotation and markup tools to convert images into
      rich networks with cellular metadata. These collections of network data and
      associated metadata, analyzed using tools from graph theory and classification
      theory, can be merged with classical systems theory, giving a more completely
      parameterized view of how biologic information processing systems are implemented
      in retina and brain. Networks have two separable features: topology and
      connection attributes. The first findings from connectomics strongly validate the
      idea that the topologies of complete retinal networks are far more complex than
      the simple schematics that emerged from classical anatomy. In particular,
      connectomics has permitted an aggressive refactoring of the retinal inner
      plexiform layer, demonstrating that network function cannot be simply inferred
      from stratification; exposing the complex geometric rules for inserting different
      cells into a shared network; revealing unexpected bidirectional signaling
      pathways between mammalian rod and cone systems; documenting selective
      feedforward systems, novel candidate signaling architectures, new coupling
      motifs, and the highly complex architecture of the mammalian AII amacrine cell.
      This is but the beginning, as the underlying principles of connectomics are
      readily transferrable to non-neural cell complexes and provide new contexts for
      assessing intercellular communication. 

PMID- 24016535
TI  - A highly sensitive prostate-specific antigen immunosensor based on gold
      nanoparticles/PAMAM dendrimer loaded on MWCNTS/chitosan/ionic liquid
      nanocomposite.
AB  - We have developed a sensitive electrochemical immunosensor for the detection of
      prostate-specific antigen (PSA), based on covalently immobilizing of anti-PSA and
      redox mediator (thionine) onto gold nanoparticles-incorporated polyamidoamine
      dendrimer (AuNPs-PAMAM) and multiwalled carbon nanotubes/ionic liquid/chitosan
      nanocomposite (MWCNTs/IL/Chit) as the support platform. The MWCNTs/IL/Chit
      nanocomposite and synthesized AuNPs were characterized using SEM and TEM
      microscopy techniques. Greatly amplified immunoassay was established by
      sandwiching the antigen between anti-PSA immobilized on the MWCNTs/IL/Chit/AuNPs
      PAMAM interface and anti-PSA labeled with horseradish peroxidase (HRP-labeled
      anti-PSA) as secondary antibody. Phtaloyl chloride (Ph) was used as linking agent
      for the subsequent immobilization of AuNPs-PAMAM onto platform and anti-PSA
      antibody and thionine onto AuNPs-PAMAM dendrimer. The increased electrocatalytic
      reduction of H2O2 by HRP was monitored by differential pulse voltammetry
      technique. Under optimized condition the calibration curve for PSA concentration
      was linear up to 80 ng ml(-1) with detection limit (signal-to-noise ratio of 3)
      of 1 pg ml(-1). AuNPs-PAMAM dendrimer as platform not only increased the amount
      of thionine and PSA antibody but also the electron transfer process accelerated
      by encapsulated AuNPs. Moreover, the proposed PSA immunosensor exhibited
      excellent stability and reproducibility. Accurate detection of PSA in human serum
      samples was demonstrated by comparison to standard ELISA assays. In addition,
      impedance technique was used as simple, rapid, low cost label free analytical
      method for PSA measurement with detection limit of 0.5 ng ml(-1) at concentration
      range up to 25 ng ml(-1). The results indicate that the present protocol is quite
      promising in developing other electrochemical immunosensors.

PMID- 24016536
TI  - "Turn off-on" fluorescent sensor for platinum drugs-DNA interactions based on
      quantum dots.
AB  - A "turn off-on" mode has been established by using the interaction between
      platinum anticancer drugs and DNA as input signal and the fluorescence reversible
      change of quantum dots (QDs) as output signal. The QDs fluorescence can be
      quenched by platinum anticancer drugs via photo-induced electron transfer
      process, rendering the system into "turn off" status, and the system can then be
      "turned on" when fluorescence is restored due to covalent conjugation between DNA
      and platinum anticancer drugs. This dual-directional fluorescence change realized
      the detection of cisplatin and DNA, overcoming the selectivity problem commonly
      existed in the traditional mono-directional fluorescence detection mode. The
      reversible fluorescent "turn off-on" mode has been further employed to study the
      interactions between DNA and different platinum anticancer drugs (cisplatin,
      oxaliplatin and carboplatin). Furthermore, the impacts of different types of DNAs
      (different in base sequence, chain length and ssDNA/dsDNA) on the mode are also
      explored. This simple, fast and convenient spectroscopic method owns promising
      applications in the study on interaction between medical molecules and DNA, and
      in biochemical detections. 

PMID- 24016537
TI  - Analysis of cell surface antigens by Surface Plasmon Resonance imaging.
AB  - Surface Plasmon Resonance (SPR) is most commonly used to measure bio-molecular
      interactions. SPR is used significantly less frequent for measuring whole cell
      interactions. Here we introduce a method to measure whole cells label free using
      the specific binding of cell surface antigens expressed on the surface of cancer
      cells and specific ligands deposited on sensor chips using an IBIS MX96 SPR
      imager (SPRi). As a model system, cells from the breast cancer cell line HS578T,
      SKBR3 and MCF7 were used. SPRi responses to Epithelial Cell Adhesion Molecule
      (EpCAM) antibody and other ligands coated on the sensor chips were measured. SPR
      curves show a response attributable to the sedimentation of the cells and a
      specific binding response on top of the initial response, the magnitude of which
      is dependent on the ligand density and the cell type used. Comparison of SPRi
      with flow cytometry showed similar EpCAM expression on MCF7, SKBR3 and HS578T
      cells. 

PMID- 24016538
TI  - Graphene oxide as nanogold carrier for ultrasensitive electrochemical immunoassay
      of Shewanella oneidensis with silver enhancement strategy.
AB  - The genus Shewanella is ubiquitous in environment and has been extensively
      studied for their applications in bioremediation. A novel immunoassay for
      ultrasensitive detection of Shewanella oneidensis was presented based on graphene
      oxide (GO) as nanogold carrier with silver enhancement strategy. The enhanced
      sensitivity was achieved by employing conjugate-featuring gold nanoparticles
      (AuNPs) and antibodies (Ab) assembled on bovine serum albumin (BSA)-modified GO
      (Ab/AuNPs/BSA/GO). After a sandwich-type antigen-antibody reaction,
      Ab/AuNPs/BSA/GO conjugate binding on the target analyte produced an enhanced
      immune-recognition response by the reduction of silver ion in the present of
      hydroquinone. The deposited silver metal was dissolved with nitric acid and
      subsequently quantified by anodic stripping voltammetry. The high AuNPs loading
      capacity of GO and the obvious signal amplification by gold-catalyzed silver
      deposition offer an excellent detection method with a wide range of linear
      relationship between 7.0 * 10(1) and 7.0 * 10(7)cfu/mL. Furthermore, the
      immunoassay developed in this work exhibited high sensitivity, acceptable
      stability and reproducibility. This simple and sensitive assay method has
      promising application in various fields for rapid detection of bacteria, protein
      and DNA.

PMID- 24016539
TI  - The E4 protein; structure, function and patterns of expression.
AB  - The papillomavirus E4 open reading frame (ORF) is contained within the E2 ORF,
      with the primary E4 gene-product (E1^E4) being translated from a spliced mRNA
      that includes the E1 initiation codon and adjacent sequences. E4 is located
      centrally within the E2 gene, in a region that encodes the E2 protein's flexible
      hinge domain. Although a number of minor E4 transcripts have been reported, it is
      the product of the abundant E1^E4 mRNA that has been most extensively analysed.
      During the papillomavirus life cycle, the E1^E4 gene products generally become
      detectable at the onset of vegetative viral genome amplification as the late
      stages of infection begin. E4 contributes to genome amplification success and
      virus synthesis, with its high level of expression suggesting additional roles in
      virus release and/or transmission. In general, E4 is easily visualised in biopsy
      material by immunostaining, and can be detected in lesions caused by diverse
      papillomavirus types, including those of dogs, rabbits and cattle as well as
      humans. The E4 protein can serve as a biomarker of active virus infection, and in
      the case of high-risk human types also disease severity. In some cutaneous
      lesions, E4 can be expressed at higher levels than the virion coat proteins, and
      can account for as much as 30% of total lesional protein content. The E4 proteins
      of the Beta, Gamma and Mu HPV types assemble into distinctive cytoplasmic, and
      sometimes nuclear, inclusion granules. In general, the E4 proteins are expressed
      before L2 and L1, with their structure and function being modified, first by
      kinases as the infected cell progresses through the S and G2 cell cycle phases,
      but also by proteases as the cell exits the cell cycle and undergoes true
      terminal differentiation. The kinases that regulate E4 also affect other viral
      proteins simultaneously, and include protein kinase A, Cyclin-dependent kinase,
      members of the MAP Kinase family and protein kinase C. For HPV16 E1^E4, these
      kinases regulate one of the E1^E4 proteins main functions, the association with
      the cellular keratin network, and eventually also its cleavage by the protease
      calpain which allows assembly into amyloid-like fibres and reorganisation of the
      keratin network. Although the E4 proteins of different HPV types appear divergent
      at the level of their primary amino acid sequence, they share a recognisable
      modular organisation and pattern of expression, which may underlie conserved
      functions and regulation. Assembly into higher-order multimers and suppression of
      cell proliferation are common to all E4 proteins examined. Although not yet
      formally demonstrated, a role in virus release and transmission remains a likely
      function for E4.

PMID- 24016540
TI  - The anti-arrhythmic effects of n-3 PUFAs.
AB  - In the past years, in vitro and animal studies have demonstrated several direct
      and indirect anti-arrhythmic effects of n-3 polyunsaturated fatty acids (n-3
      PUFAs), at least in part mediated by anti-oxidant, anti-inflammatory and
      antifibrotic properties. Several epidemiological and clinical studies have been
      conducted to investigate the eventual benefits of fish oils in the prevention of
      cardiovascular diseases. The aim of this paper is to critically review current
      evidence on the anti-arrhythmic effects of n-3 PUFAs in the prevention of sudden
      cardiac death (SCD) and atrial fibrillation (AF). Published data are conflicting,
      but some benefits have been reported in the prevention of SCD after myocardial
      infarction and of AF, generally after long-course administration. 

PMID- 24016541
TI  - Perturbations of mechanotransduction and aneurysm formation in heritable
      aortopathies.
AB  - Thoracic aortic aneurysm and dissection in young and middle aged patients is
      increasingly recognised as due to genetic aortopathy. Mutations in multiple genes
      affecting proteins in the extracellular matrix, microfibrillar structure, the
      endothelium and cell signalling pathways have been associated with thoracic
      aortic disease. The TGFbeta signalling pathway appears to play a key role in
      mediating abnormal aortic growth and aneurysm formation. A challenge remains in
      understanding how the many different gene mutations can result in deranged
      TGFbeta signalling. This review examines the functional relationships between key
      structural and signalling proteins, with reference to the need for maintenance of
      homeostasis in mechanotransduction within the aortic wall. A mechanism, through
      which perturbations in mechanotransduction, arising from different gene
      mutations, results in altered TGFbeta signalling is described. 

PMID- 24016542
TI  - Plasma adenosine release is associated with bradycardia and transient loss of
      consciousness during experimental breath-hold diving.

PMID- 24016543
TI  - Comparative analysis of red cell distribution width and high sensitivity C
      reactive protein for coronary heart disease mortality prediction in multi-ethnic
      population: findings from the 1999-2004 NHANES.
AB  - BACKGROUND: Red cell distribution width (RDW) has been shown to predict all-cause
      and cardiovascular (CVD) mortality. However, the predictive ability of RDW for
      future coronary heart disease (CHD) mortality in comparison to high sensitivity C
      reactive protein (hs-CRP) has not been assessed in a population cohort free of
      CVD. METHODS: Analysis was performed on 8,513 adult participants (age > 20 years)
      free of CVD from the National Health and Nutrition Examination Surveys 1999-2004.
      Cox-proportional hazard analyses were used to assess the role of RDW and hs-CRP
      in CHD mortality and in subgroups based on high and low RDW and hs-CRP. RESULTS:
      On adjustment for traditional risk factors (age, sex, systolic blood pressure,
      anti-hypertensive medication use, total cholesterol, high density lipoprotein
      cholesterol, lipid lowering therapy, smoking, diabetes mellitus, anemia, mean
      corpuscular volume and nutritional deficiencies), RDW [hazard ratio (HR) 1.26 95%
      Confidence Interval (CI) [1.12-1.42] p < 0.001] remained an independent
      predictor, while hs-CRP [HR 1.18 95% CI [0.98-1.41] p = 0.077] did not. On
      comparative analysis, high RDW (> 12.6%) was predictive of CHD mortality
      irrespective of hs-CRP status [hs-CRP <= 3 mg/L (HR 1.17 95% CI [1.01-1.36] p =
      0.031)] and hs-CRP > 3 mg/L (HR 1.44 95% CI [1.23-1.68] p < 0.001). Hs-CRP was
      not predictive in either high or low RDW subgroup. CONCLUSION: RDW but not hs-CRP
      was associated with CHD mortality independent of traditional risk factors in a
      cohort with no pre-existing CVD. RDW may be considered a stronger biomarker for
      CHD death than hs-CRP and needs further prospective evaluation in CVD risk
      assessment.

PMID- 24016544
TI  - A meta-analysis of the role of statins on renal outcomes in patients with chronic
      kidney disease. Is the duration of therapy important?
AB  - INTRODUCTION: The efficacy of statin treatment in chronic kidney disease (CKD)
      patients remains controversial. Therefore, we performed a meta-analysis to
      investigate whether statins modulate renal function in patients with CKD.
      METHODS: Data from Scopus, PubMed, Web of Science, and the Cochrane Central
      Register of randomized controlled trials for years 1966-December 2012 were
      searched for appropriate studies. RESULTS: Twenty trials with 6452 CKD subjects
      randomized to receive either statin or placebo were included. Statin therapy
      significantly influenced high sensitivity C-reactive protein levels in patients
      on or off dialysis [-0.28 mg/dl, 95%CI: -0.93 to -0.37; p<0.05 and -0.46 mg/dl,
      95%CI: -0.87 to -0.05; p=0.03], respectively], urinary protein (-0.77 g/24 h,
      95%CI: -1.24 to -0.29, p<0.02; this effect persisted for treatment <=12 months),
      and serum creatinine but only for long-term therapy (3 years) (-0.65 mg/dl,
      95%CI: -1.00 to -0.30; p=0.0003). The summary for standardized effect size of
      mean differences of glomerular filtration rate was 0.29 ml/min/1.73 m(2) (95%CI:
      0.01 to 0.58; p=0.04), and depended on treatment duration - a significant
      increase was observed for between 1 and 3 years of statin therapy (0.50
      ml/min/1.73 m(2), 95%CI: 0.40 to 0.60; p<0.0001), with no significant increase
      for both <=1 and >3 years of the therapy. CONCLUSION: Statins might exert
      significant renoprotective effects in CKD patients; however, benefit may depend
      on the duration of treatment. This is an issue that warrants more definitive
      investigation. More studies are necessary in dialysis patients to credibly
      evaluate the renal effects of statin therapy.

PMID- 24016545
TI  - Ibn al-Quff (1233-1286AD), genius theorist of the existence of capillaries.

PMID- 24016546
TI  - Comparison of catheter ablation and surgical ablation in patients with long
      standing persistent atrial fibrillation and rheumatic heart disease: a four-year
      follow-up study.
AB  - BACKGROUND: In our previous prospective and randomized study, we have
      demonstrated that the concomitant surgical ablation using saline-irrigated cooled
      tip radiofrequency ablation (SICTRA) system is more effective than subsequent
      circumferential pulmonary vein isolation (CPVI) combined with substrate
      modification in treating patients with long-standing persistent atrial
      fibrillation (LS-AF) and rheumatic heart disease (RHD) undergoing cardiac surgery
      during middle-term follow-up. Whether this strategy also decreases longer-term
      arrhythmia recurrence is unknown. This study describes the 4-year efficacy of
      SICTRA for these patients. Furthermore, we seek to compare the
      electrophysiological characteristics for recurrent atrial tachyarrhythmia (ATa)
      at the session of catheter ablation between two groups. METHODS: Long-term follow
      up was performed in 95 patients who underwent the catheter ablation strategy
      (n=47, Group A) or SICTRA (n=48, Group B) combined with valvular surgery for
      symptomatic LS-AF patients with RHD. RESULTS: After one procedure, Group B had a
      significantly higher freedom from ATa compared with Group A (29/48 vs 15/47,
      P=0.005) after a mean follow-up of 54 months (range 48 to 63 months). Catheter
      based mapping and ablation of recurrent ATa showed larger amounts of macro
      reentrant atrial tachycardias (ATs) in Group B and higher incidence of pulmonary
      vein (PV) recovery in Group A. After multiple catheter ablations for recurrent
      ATa, sinus rhythm (SR) could be maintained equally between two groups.
      CONCLUSIONS: Single procedure success seems to be higher with SICTRA but repeated
      catheter ablation potentially results in comparable outcomes in treating patients
      with LS-AF and RHD during long-term follow-up. More macro-reentrant ATs and more
      PV recoveries are identified to be responsible for ATa in SICTRA and catheter
      ablation group, respectively.

PMID- 24016547
TI  - Transcriptional control of regulatory T cell development and function.
AB  - Regulatory T (Treg) cells differentiate from thymocytes or peripheral T cells in
      response to host and environmental cues, culminating in induction of the
      transcription factor forkhead box P3 (Foxp3) and the Treg cell-specific
      epigenome. An intermediate amount of antigen stimulation is required to induce
      Foxp3 expression by engaging T cell receptor (TCR)-activated [e.g., nuclear
      factor (NF)-kappaB] and TCR-inhibited (e.g., Foxo) transcription factors.
      Furthermore, Treg cell differentiation is associated with attenuated Akt
      signaling, resulting in enhanced nuclear retention of Foxo1, which is
      indispensable for Treg cell function. These findings reveal that Treg cell
      lineage commitment is not only controlled by genetic and epigenetic imprinting,
      but also modulated by transcriptional programs responding to extracellular
      signals. 

PMID- 24016548
TI  - Surgical mission planning in the developing world.
AB  - Surgical missions to the developing world have been criticized for their lack of
      outcome analysis. Reported studies indicate a high rate of postoperative
      complications. An integrated pathway developed for surgical missions and a report
      of its performance in action is presented herein. Patients were optimized for
      surgery by a medical team from the UK for a minimum of 14 days preoperatively.
      They were then transferred to hospital for surgery and returned when stable. At
      the completion of the mission a junior doctor remained behind for 3 weeks to
      chart the patients' progress. Thirty case patients were treated over a 2-week
      period. The complication rate at 3 weeks postoperatively was 7/30. Twenty-two
      operations were classified as complex (over 1h with more than one flap) and eight
      as simple (under 1h with minimal flaps). Of those undergoing the simple
      operations, 2/8 encountered complications at an average of 5 days postoperatively
      (range 3-7 days). Many medical teams depart in an elevated atmosphere of
      accomplishment, which without an outcome analysis gives a false impression of
      their positive impact. Outcome analysis is essential to honestly appraise the
      effect of surgical missions. 

PMID- 24016549
TI  - Transport distraction osteogenesis as a method of reconstruction of the
      temporomandibular joint following gap arthroplasty for post-traumatic ankylosis
      in children: a clinical and radiological prospective assessment of outcome.
AB  - This clinical and radiographic study investigated the use of transport
      distraction osteogenesis in unilateral temporomandibular joint (TMJ) ankylosis
      patients. Six patients aged between 4 and 8 years were selected for the study;
      the mean preoperative maximal inter-incisal opening (MIO) was 3.5mm without
      lateral and protrusive mandibular movements. The ankylotic mass along with the
      posterior border of the ascending ramus was exposed via 'lazy-S' incision. A gap
      arthroplasty was performed, followed by a 'reverse L' osteotomy on the posterior
      border of the ramus. In-house manufactured extraoral distraction devices were
      used for this prospective study. Follow-up clinical and radiographic evaluation
      was carried out for 13-27 months after completion of the activation period. After
      a mean follow-up of 19 months, the mean MIO was 29.1mm and the lateral and
      protrusive movements changed from none to slight. Cone beam computed tomography
      images of all patients showed remodelled neocondyle created by transport
      distraction osteogenesis with no statistically significant differences observed
      for average cancellous bone density, trabecular number, and trabecular spacing
      between the neocondyle of the operated side (test) and the condyle of the non
      operated side (control). Neocondyle formation by transport distraction
      osteogenesis using the in-house distraction device is a promising treatment
      option for TMJ reconstruction in ankylosis patients. 

PMID- 24016550
TI  - Subcellular location of the coupling protein TrwB and the role of its
      transmembrane domain.
AB  - Conjugation is the most important mechanism for horizontal gene transfer and it
      is the main responsible for the successful adaptation of bacteria to the
      environment. Conjugative plasmids are the DNA molecules transferred and a
      multiprotein system encoded by the conjugative plasmid itself is necessary. The
      high number of proteins involved in the process suggests that they should have a
      defined location in the cell and therefore, they should be recruited to that
      specific point. One of these proteins is the coupling protein that plays an
      essential role in bacterial conjugation. TrwB is the coupling protein of R388
      plasmid that is divided in two domains: i) The N-terminal domain referred as
      transmembrane domain and ii) a large cytosolic domain that contains a nucleotide
      binding motif similar to other ATPases. To investigate the role of these domains
      in the subcellular location of TrwB, we constructed two mutant proteins that
      comprised the transmembrane (TrwBTM) or the cytoplasmic (TrwBDeltaN70) domain of
      TrwB. By immunofluorescence and GFP-fusion proteins we demonstrate that TrwB and
      TrwBTM mutant protein were localized to the cell pole independently of the
      remaining R388 proteins. On the contrary, a soluble mutant protein (TrwBDeltaN70)
      was localized to the cytoplasm in the absence of R388 proteins. However, in the
      presence of other R388-encoded proteins, TrwBDeltaN70 localizes uniformly to the
      cell membrane, suggesting that interactions between the cytosolic domain of TrwB
      and other membrane proteins of R388 plasmid may happen. Our results suggest that
      the transmembrane domain of TrwB leads the protein to the cell pole. 

PMID- 24016551
TI  - Computational and experimental analysis of drug binding to the Influenza M2
      channel.
AB  - The Influenza Matrix 2 (M2) protein is the target of Amantadine and Rimantadine
      which block its H(+) channel activity. However, the potential of these
      aminoadamantyls to serve as anti-flu agents is marred by the rapid resistance
      that the virus develops against them. Herein, using a cell based assay that we
      developed, we identify two new aminoadamantyl derivatives that show increased
      activity against otherwise resistant M2 variants. In order to understand the
      distinguishing binding patterns of the different blockers, we computed the
      potential of mean force of the drug binding process. The results reveal that the
      new derivatives are less mobile and bind to a larger pocket in the channel.
      Finally, such analyses may prove useful in designing new, more effective M2
      blockers as a means of curbing influenza. This article is part of a Special Issue
      entitled: Viral Membrane Proteins - Channels for Cellular Networking. 

PMID- 24016552
TI  - Midwifery retention and coverage and impact on service utilisation in
      Afghanistan.
AB  - OBJECTIVE: to measure the rate of and determine factors associated with community
      midwifery education (CME) graduate retention in public sector health care in
      Afghanistan. DESIGN: cross-sectional. SETTING: performed in public health
      facilities of 11 Afghan provinces purposively selected by geographic location and
      security conditions, between October 2011 and April 2012. Facilities were
      selected by one of two criteria: either a registered deployment site for a CME
      graduate or randomly selected through population-proportionate sampling.
      PARTICIPANTS: facility managers and midwives employed in public facilities at the
      time of data collection. MEASUREMENTS: three quantitative instruments were used:
      a facility checklist assessed staffing and service volume, and two separate
      questionnaires for midwives and facility managers, which measured employment
      duration and perceived barriers to midwife retention. FINDINGS: at 456 surveyed
      facilities, 570 midwives were interviewed. Overall, 61.3% (n=209/341) of CME
      graduates deployed in surveyed provinces were working in public sector
      facilities, whereas 36.8% were working at their assigned site. Facilities without
      midwife staff had lower average monthly volumes of antenatal care visits (14.6
      (SD +/- 22.7) versus 71.5 (SD +/- 72.5)), family planning visits (10.4 (SD+13.9)
      versus 56.8 (SD+85.0)), or facility-based deliveries (0.55 (SD +/- 2.2) versus
      15.7 (SD +/- 18.7)). Perceived reasons for leaving employment were insecurity
      (civil unrest/armed conflict) (46.4%), family disagreement (28.1%), increased
      workload without compensation (9.9%), and lack of appropriate housing (7.8%). KEY
      CONCLUSIONS: CME graduate retention in public sector positions was relatively low
      and significantly impacted by insecurity and cultural issues related to women
      working outside the home. IMPLICATIONS FOR PRACTICE: culturally appropriate
      measures are needed to attract and retain skilled female health care providers
      for rural public facilities in Afghanistan and similar settings. Advocacy to
      encourage family and community support for midwives working in rural facilities
      and providing amenities such as housing, education for children, and employment
      for the accompanying male family member are measures most likely to improve
      midwife retention.

PMID- 24016553
TI  - Efficacy of a videoconferencing intervention compared with standard postnatal
      care at primary care health centres in Catalonia.
AB  - OBJECTIVE: to evaluate the efficacy of an intervention combining
      videoconferencing and telephone contact compared to standard post partum care of
      recent mothers attending health centres in Catalonia were recorded. DESIGN:
      multicentre, randomised parallel controlled clinical trial. PARTICIPANTS AND
      SETTING: 1598 post partum women with Internet access attending eight 'Attention
      to Sexual and Reproductive Health' (Catalan acronym ASSIR) units at Primary
      Health Care centres, in Catalonia (Spain). INTERVENTION: at each of the eight
      ASSIR units, 100 women were randomly assigned to the intervention group (IG) and
      100 to the control group (CG). Women in the IG could consult midwives by
      videoconference or telephone and could also receive standard care. Women in the
      control group received standard care from midwives at their health centres or at
      home. MEASURES: number and type of visits, reasons for consultation, type of
      feeding at six weeks and women's satisfaction with the intervention on a scale of
      1 to 5. FINDINGS: 1401 women were studied (80.9% of the initial sample), 683 in
      the IG and 718 in the CG. Two hundred and seventy-six women (40.4%) used
      videoconferencing or telephone in the IG. The mean total visits, virtual and face
      to-face, was higher in IG women than in controls (2.74 versus 1.22). IG women
      made fewer visits to the health centre (mean=1) than CG women (mean=1.17). Both
      differences were statistically significant, with p<0.001 and p=0.002
      respectively. The prevalence of breast feeding was similar in the two groups (IG
      64.5%, and CG 65.4%). The mean overall satisfaction of women with midwife care
      was very high in both groups (IG 4.77, CG 4.76). CONCLUSIONS AND IMPLICATIONS FOR
      THE PRACTICE: virtual care via videoconferencing is effective for post partum
      women. It reduces the number of health centre visits and allows mothers to
      consult health staff immediately and from their own home.

PMID- 24016554
TI  - The experience of postnatal depression in West African mothers living in the
      United Kingdom: a qualitative study.
AB  - OBJECTIVE: to explore the lived experience of postnatal depression (PND) in West
      African mothers living in the United Kingdom (UK). DESIGN: using a qualitative
      design, semi-structured interviews were undertaken. Interpretative
      Phenomenological Analysis (IPA) was used to explore and analyse the data.
      SETTING: community health services within inner-city suburbs in Manchester,
      England. PARTICIPANTS: six West African mothers (Nigeria=3; Ghana=3), who were
      experiencing low mood in the postnatal period. FINDINGS: five overarching themes
      emerged: (1) conceptualising PND, (2) isolation, (3) loss of identity, (4) issues
      of trust and (5) relationships as a protective factor. Women exhibited symptoms
      of PND but did not regard it as an illness. In their view, postnatal depression
      and distress resulted from social stress. Participants stated that their cultural
      background made it difficult to disclose feelings of depression thus adversely
      influencing their help-seeking behaviour. KEY CONCLUSIONS: this is the first
      study to investigate the experiences of West African mothers with PND who live in
      the UK, and how they perceive and make sense of their experiences. The themes
      generated add to the body of existing research on PND in Black and ethnic
      minority populations and offer insight into the lived experience of West African
      women residing in England. Such insights are vital in order to deliver effective,
      culturally sensitive care. IMPLICATIONS FOR PRACTICE: these findings have
      implications on how services should be designed to increase their accessibility
      to African women, by using a community psychology approach alongside systemic and
      group interventions. Challenges to help seeking and language used to describe
      experiences are considered.

PMID- 24016555
TI  - Passage kinetics of concentrates in dairy cows measured with carbon stable
      isotopes.
AB  - Fractional passage rates form a fundamental element within modern feed evaluation
      systems for ruminants, but knowledge on feed-specific fractional passage is
      largely lacking. Commonly applied tracer techniques based on externally applied
      markers, such as chromium-mordanted neutral detergent fibre (Cr-NDF), have been
      criticised for behaving differently to feed particles. This study describes the
      use of the carbon stable isotope ratio (13C : 12C) as an internal digesta marker
      to quantify the fractional passage rate of concentrates through the digestive
      tract of dairy cows. In a crossover study, five dairy cows were fed low (24.6%)
      and high (52.6%) levels of concentrates (dry matter (DM) basis) and received a
      pulse-dosed Cr-NDF and 13C isotopes. The latter was administered orally by
      exchanging part of the dietary concentrates of low 13C natural abundance with a
      pulse dose of maize bran-based concentrates of high 13C natural abundance.
      Fractional passage rates from the rumen (K 1) and from the large intestine (K 2)
      were determined from faecal marker concentrations of Cr-NDF and of 13C in the DM
      (13C-DM), NDF (13C-NDF) and neutral detergent soluble (13C-NDS). No differences
      in K 1 estimates were found for the two concentrate levels fed but significant
      differences between markers (P<0.001) were observed. Faecal Cr-NDF excretions
      gave lower K 1 estimates (0.037-0.039/h) than 13C-DM (0.054-0.056/h) and 13C-NDF
      (0.061-0.063/h). The 13C-NDS was calculated by the difference of 13C in the DM
      and NDF, and K 1 values (0.039-0.043/h) were comparable to Cr-NDF. Total mean
      retention time was considerably higher for Cr-NDF (40.9-42.0 h) as compared to
      13C-DM and 13C-NDF (32.0-33.5 h; P<0.001). The accuracy of the curve fits for Cr
      NDF and 13C-DM and 13C-NDF was overall good (mean prediction error of 9.9-13.9%).
      Fractional passage rate of Cr-NDF was comparable to studies where this marker was
      assumed to represent the fractional passage of roughages. However, K 1 estimates
      based on the 13C : 12C ratio varied considerably from studies based on external
      markers. Our results suggest that the use of 13C isotopes as digesta passage
      markers can provide feed component-specific K 1 estimates for concentrates and
      provides new insight into passage kinetics of NDF from technologically treated
      compound feed. 

PMID- 24016556
TI  - [Significance of the multicenter clinical study of sudden hearing loss in China].

PMID- 24016557
TI  - [Prospective clinical multi-center study on the treatment of sudden deafness with
      different typings in China].
AB  - OBJECTIVE: To investigate the necessity of subtyping for the treatment of sudden
      deafness. METHODS: The international standardized clinical research methods, the
      unified design and program were used in the study. The sudden deafness patients
      between 18 to 65 years old were recruited, whose duration was less than two weeks
      with no medication. The patients were divided into four types according to the
      hearing curve: type A was acute sensorineural hearing loss in low tone
      frequencies, type B was acute sensorineural hearing loss in high tone
      frequencies, type C was acute sensorineural hearing loss in all frequencies and
      type D was total deafness. Each type had four different treatment programs, based
      on the unified designed randomized table. RESULTS: Total of 1024 cases with
      single side sudden deafness were recruited in the study by 33 hospitals in China
      from August 2007 to October 2011, including 492 male cases (48.05%), and 532
      females (51.95%). The average age was (41.2 +/- 12.8) years old. By
      classification of audiogram, among the 1024 cases, 205 cases were type A
      (20.20%), 141 cases were type B (13.77%), 402 cases were type C (39.26%), 276
      cases were type D (26.95%). The curative effects of different types were
      analyzed, type A had the highest rate of 90.73%, type C was 82.59%, type D was
      70.29% and type B had the lowest rate of 65.96%. Significant difference of
      curative rate between different types was detected (chi(2) = 231.58, P = 0.000).
      Regarding the curative results of the 1024 cases, 378 cases were recovery
      (36.91%), 229 cases were excellent better (22.36%), 198 cases were better
      (19.34%) and 219 cases were poor (21.39%). Glucocorticoid was effective for each
      type and the combined treatment was better than any single medication.
      CONCLUSIONS: Different types of the hearing curves of sudden deafness have
      different curing effect, it indicates that different types should use different
      treatments. It'is important that sudden deafness should be treated according to
      the types of the hearing curve. The type in low tone frequencies has the best
      curative effect, followed by the type in all frequencies. The type in high tone
      frequencies and the total deafness type has poor curative results.

PMID- 24016558
TI  - [Multi-center clinical study on the treatment of the low-middle frequency sudden
      hearing loss].
AB  - OBJECTIVE: To investigate and compare the short-term outcome of patients with low
      middle frequency sudden deafness treated with alone or combination treatment.
      METHODS: From August 2007 to October 2011, 205 patients with the diagnosis of low
      middle frequency sudden deafness who were from 33 different clinical centers were
      recruited. All patients were followed up for four weeks from the initial
      examination. Patients were treated with steroid , Ginaton, batroxobin
      respectively, or Ginaton and steroid combination treatment. RESULTS: The total
      effective rate was 90.73%. In Ginaton group, the total effective rate was 87.27%,
      89.19% in steroid group, 87.80% in batroxobin group, and 95.83% in Ginaton and
      steroid group. Considering the total effective rate, there was no statistical
      difference between four groups (chi(2) = 7.98, P = 0.54). The clinical cure rate
      for steroid alone was 81.01%, Ginaton alone 76.36%, batroxobin alone 68.29%, and
      Ginaton and steroid combination treatment 80.56%. There were no clinically
      significant differences between the different treatments (P > 0.05). CONCLUSIONS:
      The low-middle frequency sudden deafness tends to have a relatively favorable
      prognosis. The steroid played a good effect in the treatment. But different
      treatments either improving the microcirculation of inner ear or alleviating
      edema blood has undifferentiated results. Therefore the combination therapy may
      be more effective.

PMID- 24016559
TI  - [Multi-center study on the treatment for intermediate and high-frequency sudden
      sensorineural hearing loss].
AB  - OBJECTIVE: To analyze the therapeutic effect of treatment for intermediate and
      high-frequency sudden sensorineural hearing loss (SSNHL). METHODS: A prospective
      clinical multicentre research was conducted using international standardized
      approach of clinical research. SSNHL Cases with intermediate and high-frequency
      hearing loss, that accepted no medication from onset of hearing loss within two
      weeks duration and ages ranged between 18 and 65, were collected. All patients
      were treated by one of four treatments plans chosen by unified random table.
      RESULTS: 141 patients with intermediate and high-frequency SSNHL were recruited
      in the research. Twenty subjects were treated with lidocaine, 21 cases with
      lidocaine and hormone, 40 cases with Ginaton, and 60 cases with Ginaton and
      hormone. 42 out of 141 (29.79%) patients were total recovery, 24 (17.02%)achieved
      excellent recovery, 27 (19.15%)achieved partial recovery, and 48 (34.04%) were
      ineffective. The total effective rate was 65.96%. In lidocaine group, the total
      effective rate was 55.00%, 66.67% in lidocaine and hormone group, 67.50% in
      Ginaton group, and 68.33% in Ginaton and hormone group. Considering the total
      effective rate, there was no statistical difference between four groups (P >
      0.05). However, the recovery rate in Ginaton group was significant difference
      comparing with that in lidocaine group (P = 0.0496). 119 had concomitant symptom
      of tinnitus, and the tinnitus was improved in patients of 81.51%. With regard to
      total effective rate of tinnitus in four treatment groups, it was 57.89% (11/19)
      in lidocaine group, 100.00% (18/18) in lidocaine and hormone group, 88.57%
      (31/35) in Ginaton group, 78.72% (37/47) in Ginaton and hormone group. There was
      significant ascendancy in lidocaine and hormone group versus that in lidocaine
      group (P = 0.002) and Ginaton and hormone group (P = 0.029). And the difference
      between lidocaine and Ginaton groups was statistical significance (chi(2) =
      6.705, P < 0.05). In 43 patients with muffled symptom in aural region, 90.70% was
      partial recovery. There was no statistical difference between each groups (chi(2)
      = 5.97,P = 0.74). There were 17 with dizziness or vertigo improved in all cases.
      Another 10 patients accompanied other complaints all improved. CONCLUSIONS: for
      the treat of intermediate and high-frequency SSNHL, the therapeutic effect in
      hearing has no significantly different between single and combined drug
      therapies. Considering the recovery rate, there is an obvious advantage in
      Ginaton group compared with lidocaine group. Tinnitus is the major concomitant
      symptom in intermediate and high-frequency SSNHL, and lidocaine and hormone
      therapy should be used.

PMID- 24016560
TI  - [Multi-center study of clinical treatment on the flat type of sudden hearing
      loss].
AB  - OBJECTIVE: To investigate the effect of different treatment options for the flat
      type of sudden hearing loss. METHODS: Prospective, multi-center clinical study
      was carried out using internationally used standardized clinical research method.
      Patients with the flat type of sudden hearing loss between 18 and 65 years old,
      within two weeks duration, and without any medical treatment were recruited.
      Treatment options were randomly selected according to the designed random table.
      RESULTS: From August 2007 to October 2011, 402 patients with the flat type of
      sudden hearing loss who met the criteria (account for 39.26% of the total number
      of patients) from the 33 hospitals were collected; the total effective rate was
      82.59%, and no significant difference was detected between different treatments,
      (chi(2) = 10.95, P = 0.28). In the 402 cases, 139 were cured (34.58%); 118 were
      markedly improved (29.35%); 75 were effective (18.66%); 70 were invalid (17.41%).
      CONCLUSIONS: The therapeutic efficacy of flat type of sudden hearing loss overall
      is good; the treatment of improving the inner ear blood rheology and/or reducing
      blood fibrinogen has clinical significance; the therapeutic efficacy of using
      glucocorticoid systemically is good as well; there is no obvious difference
      between combination and single medication.

PMID- 24016561
TI  - [Multi-center study on the treatment of sudden total deafness].
AB  - OBJECTIVE: To assess the results of drug therapy in patients with severe
      idiopathic sudden sensorineural hearing loss (ISSHL) with total frequency hearing
      loss. METHODS: A prospective randomized, single blind, multi-center clinical
      trial was designed. The untreated patients with ISSHL were included, who had
      severe hearing loss (pure tone audiometry showed patients had total frequency
      hearing loss, and their mean auditory threshold of 500, 1000, 2000, 4000 Hz was
      beyond 81 dB HL), age between 18 to 65 years old, and within 14 days of the onset
      . The patients were divided into one of the four drug groups [batroxobin,
      batroxobin + ginkgo biloba leaves extract (EGb), batroxobin + EGb +
      glucocorticoids, EGb + glucocorticoids] according to the random table, and
      receive treatment. RESULTS: Totally 276 patients with unilateral severe ISSHL
      were included from 33 hospitals, from August 2007 to October 2011. Among them,
      male patients accounted for 135 (48.91%), female 141 (51.09%); the average age
      was (41.7 +/- 13.3)years. Forty cases were recovered (14.49%), 78 cases had
      marked effective (28.26%), 76 cases were effective (27.54%), 82 cases were in
      effective (29.71%), and the total effective rate was 70.29%. Among four drug
      groups, the separate effective rate were 73.33%, 61.43%, 78.31% and 67.95%
      respectively, no significant difference was found between groups (chi(2) = 9.97,P
      = 0.62). Among the four groups, the separate cure rate for hearing loss were
      11.11%, 12.86%, 16.87% and 15.38%, the glucocorticoid groups were significantly
      better than those not used. Among severe sudden deafness patients, 92.39% cases
      accompanied with tinnitus, 44.93% with dizziness (or vertigo), 50.36% with ear
      stuffy. There had no significant difference between the four groups with
      accompanied symptoms (all P > 0.05). CONCLUSIONS: It is value to give active
      treatment to sever sudden deafness patients because of an effective rate of 70%.
      However, the doctors and patients should be mind of a cure rate of only 14%.
      Steroids are recommended bacause it may play a role in the improvement rate.

PMID- 24016562
TI  - [Clinical analysis of sudden sensorineural hearing loss in patients with
      different ages].
AB  - OBJECTIVE: To investigate the clinical materials of sudden sensorineural hearing
      loss (SSNHL) in different ages of patients, and explore their clinical
      characteristics and prognosis. METHODS: A retrospective review was conducted by
      the clinical symptoms, predisposing factors and prognosis in SSNHL patients with
      different ages in the past two years (from 2008 to 2010). All patients were
      divided into three groups according to age, including Group 1 (0-18 years old),
      Group 2 (19-59 years old), and Group 3 (over 60 years old). RESULTS: Part of
      patients (28.1%) had a clear history of virus infection in Group 1. Some patients
      (18.7%) had obvious history of emotional fluctuations or fatigue before the onset
      of SSNHL. Three groups of patients with "aural fullness" symptom accounted for
      3.1%, 41.3% and 29.4% respectively. The proportions of patients with profound
      hearing loss in three groups were 62.5%, 40.0% and 33.3% respectively. Most
      patients improved hearing level during systemic internal medicine treatment.
      However, many patients (68.8%) in Group 1 showed poor therapeutic effect.
      CONCLUSIONS: SSNHL in different age stages has different clinical features. We
      can improve the personalized treatment program to this disease through the
      classification and grading treatment.

PMID- 24016563
TI  - [Objective evaluation of otolithic end organs in sudden sensorineural hearing
      loss patients].
AB  - OBJECTIVE: To observe the function of the otolithic end organs and their input
      pathways in sudden sensorineural hearing loss (SSHL) patients. METHODS: Forty
      cases of unilateral SSHL were enrolled as the observing group from May, 2011 to
      May, 2012. Thirty age- and gender-matched normal subjects were recruited as the
      control group. Both patients and normal subjects underwent conventional air
      conducted ocular vestibular evoked myogenic potential (oVEMP) and cervical
      vestibular evoked myogenic potential (cVEMP) in bilateral ears. The results were
      compared between the affected ears, the contralateral ears and the normal
      controls. RESULTS: Overall, oVEMP was elicited in 16 affected ears (40.0%), 23
      contralateral ears (57.5%) and 43 normal ears (71.7%). cVEMP could be elicited in
      25 affected ears (62.5%), 30 contralateral ears (75.0%) and 49 normal ears
      (81.7%) respectively. Significant statistical significance could be found in the
      oVEMP response rate between the affected ears and the normal ears (chi(2) =
      9.949, P = 0.002) and in the cVEMP response rate between the affected ears and
      the normal ears (chi(2) = 4.582, P = 0.032). Significant statistical difference
      could not be found in all oVEMP and cVEMP parameters (threshold, N1 latency, P1
      latency, latency interval and amplitude) among groups (P > 0.05). CONCLUSIONS:
      The otolithic vestibular end organs and their input pathways could be damaged in
      SSHL patients. Such damages could be monitored objectively by cVEMP and oVEMP
      examinations.

PMID- 24016564
TI  - [Olfactory function in patients with idiopathic rapid eye movement sleep behavior
      disorder].
AB  - OBJECTIVE: To analyze the correlation between olfactory bulb (OB) volume with
      depth of olfactory sulcus (OS) and olfactory function in patients with idiopathic
      rapid eye movement sleep behavior disorder (iRBD). METHODS: Fifty patients with
      iRBD and fifty controls were assessed with polysomnography (PSG). The results of
      olfactory function T & T testing, OB volume and depth of OS assessed with
      magnetic resonance imaging (MRI) were compared. SPSS 11.0 software was used to
      analyze the data. RESULTS: T & T olfactory testing revealed that iRBD patients
      had higher scores (3.1 +/- 0.5) than those in controls (0.6 +/- 0.1), and the
      difference was significant (t = 7.913, P < 0.05). Both men and women with iRBD
      were affected by the same extent of olfactory loss (t = 1.015, P > 0.05). OB
      volume of left side in iRBD patients was (33.75 +/- 4.11) mm(3), right side was
      (34.57 +/- 4.21) mm(3), average OB volume was (33.94 +/- 4.15) mm(3); OB volume
      of left side in controls was (51.68 +/- 7.71) mm(3), right side was (52.31 +/-
      7.77) mm(3), average OB volume was (51.94 +/- 7.74) mm(3); OB volume were lower
      in iRBD patients as compared to controls (t value were 9.013, 8.889 and 8.923,
      all P < 0.01). OS depth study revealed no statistical difference between iRBD
      patients and controls (t value were 0.923, 0.897 and 0.904, all P > 0.05).
      Olfactory discriminate threshold was negatively correlated with OB volume in iRBD
      patients (r = -0.61, P < 0.05), but no correlated with depth of OS (r = -0.24, P
      > 0.05). CONCLUSIONS: The OB volume was lower in iRBD patients as compared to
      controls. The depth of OS showed no significant changes in iRBD patients. The OB
      volume was correlated with olfactory function, while the depth of OS was no
      correlated with olfactory function.

PMID- 24016565
TI  - [Clinical analysis of 318 cases of oropharyngeal squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the clinicopathological features, treatment outcomes
      and prognosis of patients with oropharyngeal squamous cell carcinoma (OSCC).
      METHODS: Retrospective review of 318 consecutive cases with OSCC treated from
      January 1999 to December 2011. Survival rates and prognostic factors were
      calculated using the Kaplan-Meier method and multivariate Cox model survival
      analysis respectively. There were 281 males and 37 females, with a median age of
      56 years. Of the 318 cases, 163 carcinomas were from tonsil, 108 from tongue base
      and 47 from soft palate-uvula. The presenting symptoms were pharyngalgia (128
      cases, 40.3%), neck masses (71 cases, 22.3%), foreign body sensation in the
      pharynx (63 cases, 19.8%) and dental ulcer (44 cases, 13.8%). The median time
      from onset of the first symptoms until diagnosis of OSCC was 3 months. Of the 318
      OSCC, 75 were with high grade, 110 with intermediate grade and 133 with low
      grade, including 10 patients at stageI, 39 at stage II, 68 at stage III and 201
      at stage IV. RESULTS: The rates of lymph node metastasis, distant metastasis and
      second primary carcinoma were 72.3%, 13.2% and 7.9%, respectively. Of 318
      patients, 117 received radiotherapy alone, 66 underwent surgery plus
      postoperative radiotherapy, 59 underwent preoperative radiotherapy plus surgery,
      33 received concomitant chemotherapy and radiotherapy, 20 received concomitant
      molecular targeted therapy and radiotherapy, 16 underwent surgery alone and 7
      received induction chemotherapy plus radiotherapy. The 3-, 5-year overall
      survival (OS) rates were 58.4%, 50.7%, respectively, and the median overall
      survival time was 60.1 months. Ages (P = 0.034), gender(P = 0.024), smoking and
      alcohol consumptions(P = 0.008), doses of radiotherapy(P = 0.046) and clinic
      stages(P = 0.001) were independent factors for OS. CONCLUSIONS: OSCC is poor in
      prognosis, with a high incidence of cervical lymph node metastasis. Radiotherapy
      and salvage surgery are the main treatments for OSCC.

PMID- 24016566
TI  - [Influence of recombinant lentiviral vector encoding miR-15a/16-1 in biological
      features of human nasopharyngeal carcinoma CNE-2Z cells].
AB  - OBJECTIVE: To study the influence of recombinant lentiviral vector encoding miR
      15a/16-1 on biological features of human nasopharyngeal carcinoma CNE-2Z cells
      and underlying mechanisms. METHODS: GFP-positive CNE-2Z cells transfected with
      recombinant lentiviral vector were selected. The experiment was divided into
      control group, transfected group, radiotherapy group, transfected-radiotherapy
      group. Cell proliferation was analyzed by MTT. Apoptosis was detected by flow
      cytometry. Radiotherapy sensitivity of the cells in control group and transfected
      group was evaluated by colony forming experiment. The expressions of miR-15a, miR
      16-1 and bcl-2 mRNA were detected by real-time quantitative polymerase chain
      reaction (RT-qPCR). The expression of bcl-2 protein was detected by Western blot.
      The activation of Caspase-2 and Caspase-3 was evaluated by spectrophotometry.
      RESULTS: Relative expression quantities of miR-15a and miR-16-1 in infected group
      were 524.80 +/- 40.79 (t = 494.611, P = 0.000) and 466.11 +/- 40.96 (t = 386.8, P
      = 0.000), respectively. The proliferation of the cells in transfected
      radiotherapy group was the most obvious, followed by the cells in radiotherapy
      group and transfected group (F = 424.3, P = 0.000). The apoptosis rates of
      control group, transfected group, radiotherapy group and transfected-radiotherapy
      group were (2.2 +/- 1.4)%, (9.6 +/- 0.8)%, (2.9 +/- 1.1)%, and (18.6 +/- 0.7)%
      respectively(F = 158.5, P = 0.000). Clonogenic assay showed that the values of
      SF2, Do (1.473) and Dq (1.581) in transfected group were lower than those in
      control group. The relative expression levels of bcl-2 mRNA in transfected group,
      radiotherapy group, and transfected-radiotherapy group had no significant
      difference (P > 0.05). Decrease in the expression of bcl-2 protein in transfected
      radiotherapy group was most significantly, followed by that in transfected group.
      The percentages of activated Caspase-2 in control group, radiotherapy group,
      transfected group and transfected -radiotherapy group were 0.12 +/- 0.01, 0.24 +/
      0.04, 0.35 +/- 0.02, and 0.44 +/- 0.04, respectively (F = 115.500, P = 0.000).
      The percentages of activated Caspase-3 in the groups were 0.13 +/- 0.01, 0.27 +/-
      0.01, 0.43 +/- 0.02, and 0.83 +/- 0.06, respectively (F = 439.921, P = 0.000).
      CONCLUSIONS: Recombinant lentiviral vector LV-miR15a/16-1 could improve the
      expression of miR-15a and miR-16-1 in CNE-2Z cells, inhibit the proliferation of
      CNE-2Z cells, promote apoptosis and enhance the sensitivity of the cells to
      radiotherapy probably by inhibiting bcl-2 expression, activating Caspase-2 and
      Caspase-3.

PMID- 24016567
TI  - [Intratympanic versus systemic steroid treatment for idiopathic sudden hearing
      loss: a meta-analysis].
AB  - OBJECTIVE: To assess the effectiveness and safety of intratympanic versus
      systemic steroid therapy in the initial treatment of idiopathic sudden hearing
      loss. METHODS: An extensive search of the literature was performed in Pubmed and
      other available database from January, 1980 to November, 2011. After filtering by
      the criteria of Cochrane Collaboration, a meta-analysis was conducted. RESULTS:
      Nine studies met the criteria for meta-analysis, for idiopathic sudden hearing
      loss patients without diabetes received intratympanic steroid therapy, the
      improvement rate (RR = 1.11,95% CI = 0.96-1.28, P = 0.15) did not show any
      significance when compared with the patients received systemic therapy. While a
      significant difference of improvement rate occurred between intratympanic and
      systemic steroid therapy in the idiopathic sudden hearing loss patients with
      diabetes (RR = 1.24, 95% CI = 1.02-1.50, P = 0.03). CONCLUSION: For the initial
      therapy of idiopathic sudden hearing loss patients without diabetes, systemic
      steroid treatment still remains the first choice, but for the idiopathic sudden
      hearing loss patients with diabetes, intratympanic steroid treatment should be
      used for the initial treatment.

PMID- 24016568
TI  - [A Meta-analysis of prothrombin G20210A polymorphism and its risk for sudden
      sensorineural hearing loss].
AB  - OBJECTIVE: To investigate the correlation between prothrombin G20210A
      polymorphism and the risk for idiopathic sudden sensorineural hearing loss
      (ISSNHL) using Meta-analysis methodology. METHODS: Databases, including PUBMED,
      EMBASE, Cochrane Library and CBM, were searched to collect the case control
      studies on the correlation between prothrombin G20210A polymorphism and
      idiopathic sudden sensorineural hearing loss. Only high quality studies were
      included. All analysis were conducted with Review Manager Version 4.2 software.
      RESULTS: A total of 9 studies were included, involving 735 cases and 1230
      controls. The quality assessment involved 3 parts, 8 scores (totally 8 stars).
      The results showed the included studies were high-quality. Two studies were 8
      stars of quality, three studies were 7 stars, one study was 6 stars, one study
      was 5 stars, and two studies were 4 stars. Meta-analysis showed that the
      prothrombin G20210A mutation frequencies of the genotypes and alleles showed
      significant statistically difference between cases and controls [P = 0.03, OR =
      1.79, 95% CI = (1.06, 3.01); P = 0.03, OR = 1.77, 95% CI = (1.06, 2.97),
      respectively]. CONCLUSIONS: The prothrombin G20210A polymorphism might be a
      genetic risk factor for sudden hearing loss. However, this conclusion remains to
      be confirmed by high-quality, large-scale studies.

PMID- 24016569
TI  - [Relationship between inferior turbinate outfracture and the improvement of nasal
      ventilatory function].
AB  - OBJECTIVE: To discuss the relationship between structural change in nasal cavity
      and the change of nasal ventilatory function after outfracture of the inferior
      turbinate. METHODS: The inferior turbinate outfracture surgery was performed on
      50 chronic hypertrophic rhinitis patients who suffered inferior turbinate
      hypertrophy according to endoscopy and CT scan. Preoperative and postoperative
      nasal endoscopy was carried out on all patients, by which the distance from the
      inferior turbinate front mucous membrane to nasal septum (DTNS) was measured. In
      addition, CT was used to measure the minimal distance between the inside edges of
      the bilateral inferior turbinate soft tissue (MDTT) and the minimal distance
      between the bilateral inferior turbinate bones (MDTB) at the central layer of
      coronal sectional infundibulum; the minimal distance between the inferior
      turbinate at asial nasal limen (NLDT); inferior turbinate thickness (ITT). In
      this way, the change in the structure of nasal cavity was evaluated. Acoustic
      rhinometry and rhinomanometry were utilized to evaluate the ventilatory function
      of the nasal cavity objectively. Visual analogue scale (VAS) was applied to
      evaluate the severity of preoperative and postoperative nasal obstruction
      subjectively. The test data were used to perform match t-test; Spearman rank
      correlation was adopted to evaluate the relationship between patients' bilateral
      VAS and nasal inspiratory effective resistance (IER),nasal expiratory effective
      resistance (EER) and DTNS. The relationship between the total resistance of nasal
      inspiratory phase as well as the total resistance of nasal expiratory phase and
      MDTT and MDTB was analyzed. SPSS 20.0 software was used to analyze the data.
      RESULTS: The preoperative data showed that rightward DTNS was (0.12 +/- 0.07) cm,
      leftward DTNS was (0.10 +/- 0.07) cm and MDTT was (0.70 +/- 0.13) cm, and
      postoperative data showed that rightward DTNS was (0.47 +/- 0.27) cm, leftward
      DTNS was (0.43 +/- 0.15) cm, and MDTT was (1.05 +/- 0.15) cm. Significant
      differences existed in rightward DTNS, leftward DTNS and MDTT between pre-and
      post operative data (t values were -8.827, -8.590, -17.525, all P < 0.05).
      According to the preoperative and postoperative comparison, the difference in
      MDTB, NLDT, rightward ITT, leftward ITT, IER, EER, 0-5 cm nasal cavity volume (0
      5 cm NCV), nasal minimal cross-sectional area (NMCA), rightward VAS and leftward
      VAS had statistical significance (t values were -23.562, -8.374, 8.693, 6.684,
      12.021, 14.510, -6.074, -2.285, 14.042 and 9.925, respectively, all P < 0.05).
      Patients' bilateral VAS grades had a positive relationship with IER and EER (left
      side: r values were 0.541 and 0.660, respectively,right side: r values were 0.940
      and 0.688, respectively, all P < 0.05). Additionally, patients' VAS had a
      negative relationship with DTNS (r value was -0.861, P < 0.05). Besides,the total
      resistance of nasal inspiratory phase had a negative relationship with both MDTT
      and MDTB (r values were -0.565 and -0.546,respectively, all P < 0.05). The total
      resistance of nasal expiratory phase had a negative relationship with both MDTT
      and MDTB (r values were -0.562 and -0.546, all P <0.05). CONCLUSION: The inferior
      turbinate outfracture surgery was an ideal surgical method by which nasal cavity
      could be broadened and nasal ventilatory function improved.

PMID- 24016571
TI  - [Fractured tracheostomy tubes in the tracheo-bronchial tree: a case report and
      review of the literature].

PMID- 24016570
TI  - [Clinical observation of supracricoid partial laryngectomy].
AB  - OBJECTIVE: To evaluate clinical outcomes and pronouncing and swallowing functions
      after supracricoid partial laryngectomy (SCPL). METHOD: Eight-five cases
      underwent supracricoid partial laryngectomy from 1990 to 2008 were reviewed.
      RESULTS: The 3- and 5-year accumulative survival rates were 90.4% and 81.6%,
      respectively. 97.6% (83/85) patients were decannulated. 89.4% (76/85) were able
      to eat normally within 6 weeks after surgery and the swallowing functions in the
      rest patients were recovered by training in different time after surgery. Fiber
      laryngoscope showed the reconstructed throats could close well with good
      swallowing functions six months after the operation. CONCLUSION: SCPL is a good
      choice in selected cases with laryngeal cancer, with satisfactory pronouncing and
      swallowing functions after surgery.

PMID- 24016572
TI  - [Organ distribution and management of earthquake trauma to head and neck].

PMID- 24016573
TI  - [Advances in diagnosis and treatment of sudden deafness].

PMID- 24016574
TI  - [Reading and thinking of "Clinical Practice Guideline: Sudden Hearing Loss"
      issued by American Academy of Otolaryngology-Head and Neck Surgery].

PMID- 24016575
TI  - Ligase chain reaction amplification for sensitive electrochemiluminescent
      detection of single nucleotide polymorphisms.
AB  - Single nucleotide polymorphisms are the most common type of genetic variations
      among human beings and can serve as biomarkers for various types of diseases. In
      this work, based on ligase chain reaction amplification for the production of
      massive hemin/G-quadruplex DNAzymes to quench the electrochemiluminescent (ECL)
      emission of quantum dots (QDs), a universal and sensitive single nucleotide
      polymorphism detection method is described. During the ligase chain reaction
      process, the mutant K-ras target gene is recycled and exponentially duplicated,
      leading to the attachment of numerous G-rich sequences on the QD-embedded sensing
      surface. Upon the addition of the assistant sequences and hemin, numerous hemin/G
      quadruplex DNAzymes are formed, which consume the dissolved oxygen in the
      detection buffer and result in significant quenching of QD ECL emission for
      sensitive single nucleotide polymorphism determination. The developed method
      shows a linear range of 50 fM to 50 pM and an estimated detection limit of 45 fM
      for the mutant K-ras gene. The proposed strategy also exhibits high selectivity
      towards the mutant K-ras gene against the co-existence of 10(3)-fold excess of
      the wild-type K-ras gene, which makes our method a useful addition to the
      alternatives for single nucleotide polymorphism monitoring.

PMID- 24016576
TI  - Determination of mercurial species in fish by inductively coupled plasma mass
      spectrometry with anion exchange chromatographic separation.
AB  - This work demonstrated the feasibility of mercury speciation analysis by anion
      exchange chromatographic separation with inductively coupled plasma mass
      spectrometry detection. For the first time, by complexing with the mobile phase
      containing 3-mercapto-1-propanesulfonate into negatively charged complexes, fast
      separation of inorganic mercury (Hg(2+)), monomethylmercury (MeHg), ethylmercury
      (EtHg) and phenylmercury (PhHg) was achieved within 5 min on a 12.5-mm strong
      anion exchange column. The detection limits for Hg(2+), MeHg, EtHg and PhHg were
      0.008, 0.024, 0.029 and 0.034 MUg L(-1), respectively. The relative standard
      deviations of peak height and peak area (5.0 MUg L(-1) for each Hg species) were
      all below 3%. The determined contents of Hg(2+), MeHg and total Hg in a certified
      reference material of fish tissue by the proposed method were in good accordance
      with the certified values with satisfactory recoveries. The relative errors for
      determining MeHg and total mercury were -2.4% and -1.2%, respectively, with an
      acceptable range for spike recoveries of 94-101%. Mercury speciation in 11 fish
      samples were then analyzed after the pretreated procedure. The mercury contents
      in all fish samples analyzed were found compliant with the criteria of the
      National Standards of China.

PMID- 24016577
TI  - High sensitivity chemiluminescence enzyme immunoassay for detecting
      staphylococcal enterotoxin A in multi-matrices.
AB  - In this study, detection of staphylococcal enterotoxin A (SEA) in multi-matrices
      using a highly sensitive and specific microplate chemiluminescence enzyme
      immunoassay (CLEIA) has been established. A pair of monoclonal antibodies (mAbs)
      was selected from 37 anti-SEA mAbs by pairwise analysis, and the experimental
      conditions of the CLEIA were optimized. This CLEIA exhibited high performance
      with a wide dynamic range from 6.4 pg mL(-1) to 1600 pg mL(-1), and the measured
      low limit of detection (LOD) was 3.2 pg mL(-1). No cross-reactivity was observed
      when this method was applied to test SEB, SEC1, and SED. It has also been
      successfully applied for analyzing SEA in a variety of environmental, biological,
      and clinical matrices, such as sewage, tap water, river water, roast beef, peanut
      butter, cured ham, 10% nonfat dry milk, milk, orange juice, human urine, and
      serum. Thus, the highly sensitive and SEA-specific CLEIA should make it
      attractive for quantifying SEA in public health and diagnosis in near future.

PMID- 24016578
TI  - Determination and visualization of rotational ambiguity in four-component
      systems.
AB  - One of the main problems that limit the use of model-free analysis methods for
      the resolution of multivariate data is that usually there is rotational ambiguity
      in the result. While methods for the complete definition of rotational ambiguity
      for two- and three-component systems have been published recently, the
      comprehensive and general resolution of rotational ambiguity for four-component
      systems has eluded chemists for several decades. We have developed an extension
      of self-modelling curve resolution for a mixture of four-components. The
      performance of the method was verified by applying it to resolve simulated and
      real data sets. 

PMID- 24016579
TI  - Practical approaches to principal component analysis for simultaneously dealing
      with missing and censored elements in chemical data.
AB  - Multivariate chemical data often contain elements that are missing completely at
      random and the so-called left-censored elements whose values are only known to be
      below a definite threshold value (reporting limit). In the last several years,
      attention has been paid to developing methods for dealing with data containing
      missing elements and those that can handle data with missing elements and
      outliers. However, processing data with both missing and left-censored elements
      is still an ongoing problem. The aim of this work was to investigate which method
      is most suitable for handling left-censored and missing completely at random
      elements that are present simultaneously in chemical data by using a comparison
      of the generalized nonlinear iterative partial least squares (NIPALS(1))
      algorithm that has been recently proposed, methods that include uncertainty
      information like maximum likelihood principal component analysis, MLPCA(2), and
      replacement methods. The results of the Monte Carlo simulation study for
      artificial and real data sets showed that substitution with half of the reporting
      limit can be used when the percentage of left-censored elements per variable is
      up to 30-40%. The generalized NIPALS algorithm is generally recommended for a
      large percentage of left-censored elements per variable and particularly when a
      large number of variables are censored. The expectation-maximization approach
      applied to data with censored elements substituted with half of the reporting
      limits can be a strategy for dealing with missing and left-censored elements in
      data, but if the converge criterion is not fulfilled, then the generalized NIPALS
      algorithm can be applied. 

PMID- 24016580
TI  - Multivariate linear regression with missing values.
AB  - This contribution presents and discusses an efficient algorithm for multivariate
      linear regression analysis of data sets with missing values. The algorithm is
      based on the insight that multivariate linear regression can be formulated as a
      set of individual univariate linear regressions. All available information is
      used and the calculations are explicit. The only restriction is that the
      independent variable matrix has to be non-singular. There is no need for
      imputation of interpolated or otherwise guessed values which require subsequent
      iterative refinement. 

PMID- 24016581
TI  - Low-potential amperometric determination of purine derivatives through surface
      oxide regeneration method.
AB  - This article described a novel amperometry which can be used for determination of
      purine derivatives including uric acid, xanthine, hypoxanthine, guanine, and
      adenine without surface contamination. By applying a constant potential of -0.125
      V (vs. Ag/AgCl) in a flow injection system, the chelating capability of these
      purine derivatives converts the cuprous oxide layer into a soluble complex. This
      behavior would dissolve the passive oxide layer and expose the bottom copper
      layer to the solution, subsequently; an oxidation current which attributed to the
      regeneration of the original cuprous oxide layer is used to reflect the
      concentration of these purine derivatives. In a 50mM phosphate buffer, pH 7.0,
      this approach provides a high sensitivity with LOQ of sub-micro molar level of
      five purines and high stability with a RSD of 2.5% for 10 MUM xanthine (N=12).
      This method does not suffer from most biological species including ascorbic acid,
      acetaminophen, creatine, dopamine, sarcosine, ammonium ion, chloride ion, and
      urea at equal or higher than its physiological concentration.

PMID- 24016583
TI  - Adaptation of a load-inject valve for a flow injection chemiluminescence system
      enabling dual-reagent injection enhances understanding of environmental Fenton
      chemistry.
AB  - Environmental Fenton chemistry has been poorly constrained within the marine
      environment at a multi-component level. A simple, unique, reconfiguration of a
      flow-injection analytical system combined with luminol chemiluminescence allows
      quasi-simultaneously the measurement, using a single load-inject valve and a
      single photon multiplier tube, of reduced iron, Fe(II), and hydrogen peroxide.
      The system enables rapid, every 22s, measurements with good accuracy at
      environmentally relevant concentrations, less than 5% relative standard
      deviations on both a 5 nM Fe(II) standard and a 60 nM hydrogen peroxide standard.
      Limits of detection were as low as 40 pM Fe(II) and 100 pM hydrogen peroxide. The
      system showed excellent capability by measuring from within an organic rich
      seawater the photochemically induced production of Fe(II) and hydrogen peroxide
      and their subsequent cycling and Fenton like interactions.

PMID- 24016582
TI  - Maximizing recovery of water-soluble proteins through acetone precipitation.
AB  - Solvent precipitation is commonly used to purify protein samples, as seen with
      the removal of sodium dodecyl sulfate through acetone precipitation. However, in
      its current practice, protein loss is believed to be an inevitable consequence of
      acetone precipitation. We herein provide an in depth characterization of protein
      recovery through acetone precipitation. In 80% acetone, the precipitation
      efficiency for six of 10 protein standards was poor (ca. <=15%). Poor recovery
      was also observed for proteome extracts, including bacterial and mammalian cells.
      As shown in this work, increasing the ionic strength of the solution dramatically
      improves the precipitation efficiency of individual proteins, and proteome
      mixtures (ca. 80-100% yield). This is obtained by including 1-30 mM NaCl,
      together with acetone (50-80%) which maximizes protein precipitation efficiency.
      The amount of salt required to restore the recovery correlates with the amount of
      protein in the sample, as well as the intrinsic protein charge, and the
      dielectric strength of the solution. This synergistic approach to protein
      precipitation in acetone with salt is consistent with a model of ion pairing in
      organic solvent, and establishes an improved method to recover proteins and
      proteome mixtures in high yield.

PMID- 24016584
TI  - New membraneless vaporization unit coupled with flow systems for analysis of
      ethanol.
AB  - This work presents the development of a new design for a membraneless
      vaporization (MBL-VP) unit, called dual chamber MBL-VP for measurement of
      volatile compounds. With this unit, exact volumes of sample and reagent are
      introduced into their respective cone-shaped chambers from the base of the cones.
      Diffusion of volatile analyte then takes place. After an appropriate time
      interval, the acceptor solution is withdrawn from the chamber into the detector
      flow-cell, while the sample solution is withdrawn to waste. Unlike the previous
      MBL-VP design, problems with overflow of solutions are eliminated by precise
      control of the input volume to be less than the volume of the chamber. The
      developed flow system with the dual chamber MBL-VP unit was applied to the
      determination of the ethanol content of various liquid samples, using the
      oxidation reaction between potassium dichromate and the diffused ethanol. In
      addition, in order to accelerate the gas diffusion process, the donor chamber was
      aerated. As the result, relatively short analysis time of 144 s was achieved for
      ethanol content in the range of 5-50% (v/v). The proposed method was successfully
      validated against a gas chromatographic method for 17 alcoholic samples.
      Percentage recovery was in the range of 96-109%.

PMID- 24016585
TI  - Droplet-based microfluidics for dose-response assay of enzyme inhibitors by
      electrochemical method.
AB  - A simple but robust droplet-based microfluidic system was developed for dose
      response enzyme inhibition assay by combining concentration gradient generation
      method with electrochemical detection method. A slotted-vials array and a tapered
      tip capillary were used for reagents introduction and concentration gradient
      generation, and a polydimethylsiloxane (PDMS) microfluidic chip integrated with
      microelectrodes was used for droplet generation and electrochemical detection.
      Effects of oil flow rate and surfactant on electrochemical sensing were
      investigated. This system was validated by measuring dose-response curves of
      three types of acetylcholinesterase (AChE) inhibitors, including carbamate
      pesticide, organophosphorus pesticide, and therapeutic drugs regulating
      Alzheimer's disease. Carbaryl, chlorpyrifos, and tacrine were used as model
      analytes, respectively, and their IC50 (half maximal inhibitory concentration)
      values were determined. A whole enzyme inhibition assay was completed in 6 min,
      and the total consumption of reagents was less than 5 MUL. This microfluidic
      system is applicable to many biochemical reactions, such as drug screening and
      kinetic studies, as long as one of the reactants or products is electrochemically
      active.

PMID- 24016586
TI  - Versatile lipid profiling by liquid chromatography-high resolution mass
      spectrometry using all ion fragmentation and polarity switching. Preliminary
      application for serum samples phenotyping related to canine mammary cancer.
AB  - Lipids represent an extended class of substances characterized by such high
      variety and complexity that makes their unified analyses by liquid chromatography
      coupled to either high resolution or tandem mass spectrometry (LC-HRMS or LC
      MS/MS) a real challenge. In the present study, a new versatile methodology
      associating ultra high performance liquid chromatography coupled to high
      resolution tandem mass spectrometry (UHPLC-HRMS/MS) have been developed for a
      comprehensive analysis of lipids. The use of polarity switching and "all ion
      fragmentation" (AIF) have been two action levels particularly exploited to
      finally permit the detection and identification of a multi-class and multi
      analyte extended range of lipids in a single run. For identification purposes,
      both higher energy collision dissociation (HCD) and in-source CID (collision
      induced dissociation) fragmentation were evaluated in order to obtain information
      about the precursor and product ions in the same spectra. This approach provides
      both class-specific and lipid-specific fragments, enhancing lipid identification.
      Finally, the developed method was applied for differential phenotyping of serum
      samples collected from pet dogs developing spontaneous malignant mammary tumors
      and health controls. A biological signature associated with the presence of
      cancer was then successfully revealed from this lipidome analysis, which required
      to be further investigated and confirmed at larger scale. 

PMID- 24016587
TI  - Performance monitoring of a mammalian cell based bioprocess using Raman
      spectroscopy.
AB  - Being able to predict the final product yield at all stages in long-running,
      industrial, mammalian cell culture processes is vital for both operational
      efficiency, process consistency, and the implementation of quality by design
      (QbD) practices. Here we used Raman spectroscopy to monitor (in terms of
      glycoprotein yield prediction) a fed-batch fermentation from start to finish.
      Raman data were collected from 12 different time points in a Chinese hamster
      ovary (CHO) based manufacturing process and across 37 separate production runs.
      The samples comprised of clarified bioprocess broths extracted from the CHO cell
      based process with varying amounts of fresh and spent cell culture media.
      Competitive adaptive reweighted sampling (CoAdReS) and ant colony optimization
      (ACO) variable selection methods were used to enhance the predictive ability of
      the chemometric models by removing unnecessary spectral information. Using
      CoAdReS accurate prediction models (relative error of predictions between 2.1%
      and 3.3%) were built for the final glycoprotein yield at every stage of the
      bioprocess from small scale up to the final 5000 L bioreactor. This result
      reinforces our previous studies which indicate that media quality is one of the
      most significant factors determining the efficiency of industrial CHO-cell
      processes. This Raman based approach could thus be used to manage production in
      terms of selecting which small scale batches are progressed to large-scale
      manufacture, thus improving process efficiency significantly.

PMID- 24016588
TI  - Co3O4-reduced graphene oxide nanocomposite as an effective peroxidase mimetic and
      its application in visual biosensing of glucose.
AB  - The well-dispersed Co3O4 nanoparticles on reduced graphene oxide (rGO) surfaces
      were successfully prepared by in situ controlled nucleation of Co3O4 NPs on GO
      sheets and subsequent in situ reduction of GO by low temperature hydrothermal
      reaction in ethanol media. The as-prepared Co3O4/rGO nanocomposites were
      characterized by transmission electron microscopy (TEM), scanning electron
      microscope (SEM), thermogravimetry (TG), X-ray diffraction (XRD) and FT-IR
      spectra. It was found that the Co3O4 NPs were successfully decorated and well
      dispersed on the surface of rGO sheet without agglomeration. We discovered that
      the Co3O4/rGO nanocomposites possess intrinsic peroxidase-like activity and
      catalase-like activity, and could catalytically oxidize 3,3',5,5'
      tetramethylbenzidine (TMB) by hydrogen peroxide (H2O2) to produce a intensified
      colour reaction. Results of electron spin resonance (ESR) experiments
      demonstrated that the Co3O4/rGO nanocomposites showed catalytic ability to H2O2
      decomposition into OH radicals. On this basis, a simple and selective method for
      glucose detection was developed by coupling the oxidation of glucose catalyzed by
      glucose oxidase (GOx). As low as 1*10(-6) mol L(-1) glucose could be detected
      with a linear range from 1*10(-6) to 1*10(-4) mol L(-1). The visual detection of
      glucose can be realized easily through the observable color change from colorless
      to blue by the naked eyes without any instrumentation or complicated design. Our
      research results also suggest a simple route for the facile preparation of a
      highly active nanoparticles-based enzyme mimetics on proper supporting materials.

PMID- 24016589
TI  - Near infrared emission photometer for measuring the oxidative stability of edible
      oils.
AB  - Near infrared emission spectroscopy (NIRES) allows the determination of the
      induction time (IT) of edible oils in accelerated oxidation experiments by
      monitoring the emissivity of a band at 2900 nm, which corresponds to the
      formation of hydroperoxides. In this work, a new near infrared emission
      photometer dedicated to the determination of oxidative stability is described.
      The photometer presents several advantages compared to the previously reported
      NIRES instrument, such as lower cost and extreme simplicity of design and
      maintenance. The results obtained in the evaluation of the proposed instrument
      were compared with the official Rancimat method and instrument. The significant
      advantages include: faster analysis, lower sample consumption and operational
      simplicity. It is demonstrated that the procedure for determination of oxidative
      stability of oils can be significantly simplified and performed by measuring the
      sample emission at only one spectral region centered at 2900 nm. Also, the
      proposed instrument and method present precision equivalent to the Rancimat
      method (coefficient of variation=5.0%). A significant correlation between the
      methods has been found (R(2)=0.81).

PMID- 24016591
TI  - Synthesis of palladium nanoparticles on organically modified silica: application
      to design of a solid-state electrochemiluminescence sensor for highly sensitive
      determination of imipramine.
AB  - Organically modified silica substrate containing amine and vinyl functional
      groups were used for reduction and stabilization of palladium nanoparticles.
      Uniform spherical nanoparticles of palladium with average diameter of 10 nm were
      formed on silica substrate by direct contact of the substrate with an aqueous
      solution of palladium precursor, without the addition of any chemical reducer.
      Moreover, a sensitive and selective solid state electrochemiluminescence sensor
      was fabricated for the determination of imipramine, based on Ru(bpy)3(2+)
      palladium nanoparticles doped carbon ionic liquid electrode. In this process,
      imipramine acts as a co-reactant for Ru(bpy)3(2+). It is believed that the
      enhancement of the electrochemiluminescence signal in the presence of palladium
      nanoparticles in the composite is due to palladium catalytic effect on
      electrochemical and also chemical process involved in formation of Ru(byp)3(2+)*.
      In addition, the results confirmed that, the rigid composite electrode shows the
      characteristic of microelectrode arrays. The proposed method was applied to the
      determination of imipramine in tablets and urine samples. The
      electrochemiluminescence intensity showed good linearity with the imipramine
      concentration from 1-100 pM, with a detection limit of 0.1 pM.

PMID- 24016590
TI  - Improved porous silicon microarray based prostate specific antigen immunoassay by
      optimized surface density of the capture antibody.
AB  - Enriching the surface density of immobilized capture antibodies enhances the
      detection signal of antibody sandwich microarrays. In this study, we improved the
      detection sensitivity of our previously developed P-Si (porous silicon) antibody
      microarray by optimizing concentrations of the capturing antibody. We
      investigated immunoassays using a P-Si microarray at three different capture
      antibody (PSA - prostate specific antigen) concentrations, analyzing the
      influence of the antibody density on the assay detection sensitivity. The LOD
      (limit of detection) for PSA was 2.5 ng mL(-1), 80 pg mL(-1), and 800 fg mL(-1)
      when arraying the PSA antibody, H117 at the concentration 15 MUg mL(-1), 35 MUg
      mL(-1), and 154 MUg mL(-1), respectively. We further investigated PSA spiked into
      human female serum in the range of 800 fg mL(-1) to 500 ng mL(-1). The microarray
      showed a LOD of 800 fg mL(-1) and a dynamic range of 800 fg mL(-1) to 80 ng mL(
      1) in serum spiked samples.

PMID- 24016592
TI  - Chemisorption assembly of Au nanorods on mercaptosilanized glass substrate for
      label-free nanoplasmon biochip.
AB  - The fabrication of a localized surface plasmon resonance nanosensor in a chip
      based format that utilizes Au nanorods (GNRs) as the optical transducer were
      systematically studied. (3-mercaptopropyl)trimethoxysilane (MPTMS) modified glass
      substrate offers GNR deposition with maximal sensitivity to local refractive
      index changes, which subsequently results in better optical recognition of
      receptor-analyte binding. Kinetics governing the mass transport and chemisorption
      of nanorods from bulk to solid surface can be dynamically controlled in a
      predictable fashion. We demonstrate that slight aggregation induced by a low
      ionic strength (5 mM NaCl) can facilitate the nanorod assembly to result in a
      dense, well-distributed surface monolayer. In high ionic media (e.g. 40-80 mM),
      anions present electrostatically bind with the positively charged
      cetyltrimethylammonium bromide (CTAB) surrounding nanorod surfaces, thereby
      leading to instability with heavy aggregation in solution. However, once
      chemically bound on silanized substrates, the nanorods exhibit excellent
      stability in physiological buffer where high amount of ionic species are present.
      The fundamental study is followed by demonstration of a practical application of
      the fabricated biochip in label-free detection based on GNR wavelength shift of
      the longitudinal palsmon maxima as the optical signature of human IgG model
      detection.

PMID- 24016593
TI  - Quantitative analysis of biodiesel in blends of biodiesel and conventional diesel
      by comprehensive two-dimensional gas chromatography and multivariate curve
      resolution.
AB  - In this paper, a method to determine the composition of blends of biodiesel with
      mineral diesel (BXX) by multivariate curve resolution with Alternating Least
      Squares (MRC-ALS) combined to comprehensive two-dimensional gas chromatography
      with Flame Ionization Detection (GC*GC-FID) is presented. Chromatographic
      profiles of BXX blends produced with biodiesels from different sources were used
      as input data. An initial evaluation carried out after multiway principal
      component analysis (MPCA) was used to reveal regions of the chromatograms were
      the signal was likely to be dependent on the concentration of biodiesel,
      regardless its vegetable source. After this preliminary step MCR-ALS modeling was
      carried out only using relevant parts of the chromatograms. The resulting
      procedure was able to predict accurately the concentration of biodiesel in the
      BXX samples regardless of its origin. 

PMID- 24016595
TI  - Seroprevalence of Toxoplasma gondii and Trichinella spiralis infections in wild
      boars (Sus scrofa) in Korea.
AB  - Toxoplasma gondii and Trichinella spiralis are important zoonotic pathogens with
      worldwide distributions. In Korea, several outbreaks of human toxoplasmosis and
      trichinellosis due to the consumption of infected wild animals have been
      reported. The purpose of this study was to determine the seroprevalence of T.
      gondii and T. spiralis infections in wild boars killed in Korea from December
      2009 to October 2011. A total of 521 wild boars hunted in eight provinces were
      examined for antibodies to T. gondii and T. spiralis by using commercial ELISA
      kits. Overall, 25.1% of serum samples from individual boars were seropositive for
      T. gondii and 1.7% were seropositive for T. spiralis. Seropositive for T. gondii
      was found in the boars in all the eight provinces investigated and for T.
      spiralis in four provinces. This is the first report on the seroprevalence of T.
      gondii and T. spiralis infections in wild boars in Korea. The consumption of
      undercooked wild boar meat may expose humans to a high risk of infection. 

PMID- 24016596
TI  - Identification of phospholipase activity in Rhinella arenarum sperm extract
      capable of inducing oocyte activation.
AB  - Egg activation, which includes cortical granule exocytosis, resumption and
      completion of meiosis and pronuclear formation culminates in the first mitotic
      cleavage. However, the mechanism through which the fertilizing sperm induces this
      phenomenon is still controversial. We investigated the effect of the
      microinjection of homologous sperm soluble fractions obtained by fast protein
      liquid chromatography (FPLC) from reacted sperm (without acrosome) and non
      reacted sperm on the activation of Rhinella arenarum oocytes matured in vitro.
      The FPLC-purified sperm fraction obtained from reacted or non-reacted sperm is
      able to induce oocyte activation when it is microinjected. This fraction has a 24
      kDa protein and showed phospholipase C (PLC) activity in vitro, which was
      inhibited by D-609 but not by n-butanol or neomycin, suggesting that it is a PLC
      that is specific for phosphatidylcholine (PC-PLC). The assays conducted using
      inhibitors of inositol triphosphate (IP3) and ryanodine receptors (RyRs) indicate
      that the fraction with biological activity would act mainly through the cADPr
      (cyclic ADP ribose) pathway. Moreover, protein kinase C (PKC) inhibition blocks
      the activation produced by the same fraction. Immunocytochemical studies indicate
      that this PC-PLC can be found throughout the sperm head.

PMID- 24016594
TI  - Lung cancer stem cells: Molecular features and therapeutic targets.
AB  - Lung cancers are highly heterogeneous and resistant to available therapeutic
      agents, with a five year survival rate of less than 15%. Despite significant
      advances in our knowledge of the genetic alterations and aberrations in signaling
      pathways, it has been difficult to determine the basis of lung cancer
      heterogeneity and drug resistance. Cancer stem cell model has attracted a
      significant amount of attention in recent years as a viable explanation for the
      heterogeneity, drug resistance, dormancy and recurrence and metastasis of various
      tumors. At the same time, cancer stem cells have been relatively less
      characterized in lung cancers. This review summarizes the current understanding
      of lung cancer stem cells, including their molecular features and signaling
      pathways that drive their stemness. This review also discusses the potential
      startegies to inhibit the signaling pathways driving stemness, in an effort to
      eradicate these cells to combat lung cancer. 

PMID- 24016597
TI  - Metabolism modifications and apoptosis induction after CellfoodTM administration
      to leukemia cell lines.
AB  - BACKGROUND: CellfoodTM (CF) is a nutritional supplement containing deuterium
      sulphate, minerals, amino acids, and enzymes, with well documented antioxidant
      properties. Its organic and inorganic components are extracted from the red algae
      Lithothamnion calcareum, whose mineral extract has shown growth-inhibitory effect
      both on in vitro and in vivo models. The purpose of this study was to evaluate
      the antiproliferative effects of CF on leukemic cells. In fact, according to its
      capacity to modulate O2 availability and to improve mitochondrial respiratory
      metabolism, we wondered if CF could affect cancer cell metabolism making cells
      susceptible to apoptosis. METHODS: Three leukemic cell lines, Jurkat, U937, and
      K562, were treated with CF 5 MUl/ml up to 72 hours. Cell viability, apoptosis
      (i.e. caspase-3 activity and DNA fragmentation), hypoxia inducible factor 1 alpha
      (HIF-1alpha) concentration, glucose transporter 1 (GLUT-1) expression, lactate
      dehydrogenase (LDH) activity and lactate release in the culture medium were
      detected and compared with untreated cells. RESULTS: CF significantly inhibited
      leukemic cell viability by promoting cell apoptosis, as revealed by caspase-3
      activation and DNA laddering. In particular, CF treated cells showed lower HIF
      1alpha levels and lower GLUT-1 expression as compared to untreated cells. At the
      same time, CF was able to reduce LDH activity and, consequently, the amount of
      lactate released in the extracellular environment. CONCLUSIONS: We supplied
      evidence for an antiproliferative effect of CF on leukemia cell lines by inducing
      cell death through an apoptotic mechanism and by altering cancer cell metabolism
      through HIF-1alpha and GLUT-1 regulation. Thanks to its antioxidative and
      proapoptotic properties, CF might be a good candidate for cancer prevention.

PMID- 24016598
TI  - Factors affecting the integration of immigrant nurses into the nursing workforce:
      A double hermeneutic study.
AB  - BACKGROUND: Variations in nursing practice and communication difficulties pose a
      challenge for the successful integration into the workforce of immigrant nurses.
      Evidence for this is found in cultural clashes, interpersonal conflicts,
      communication problems, prejudiced attitudes and discrimination towards immigrant
      nurses. While the evidence shows that integrating immigrant nurses into the
      nursing workforce is shaped by factors that are socially constructed, studies
      that examine social structures affecting workforce integration are sparse.
      OBJECTIVES: The aim of this study was to examine interplaying relationships
      between social structures and nurses' actions that either enabled or inhibited
      workforce integration in hospital settings. DESIGN: Giddens' Structuration Theory
      with double hermeneutic methodology was used to interpret 24 immigrant and 20
      senior nurses' perceptions of factors affecting workforce integration. RESULTS:
      Four themes were identified from the data. These were: (1) employer-sponsored
      visa as a constraint on adaptation, (2) two-way learning and adaptation in
      multicultural teams, (3) unacknowledged experiences and expertise as barriers to
      integration, and (4) unquestioned sub-group norms as barriers for group cohesion.
      The themes presented a critical perspective that unsuitable social structures
      (policies and resources) constrained nurses' performance in workforce integration
      in the context of nurse immigration. The direction of structural changes needed
      to improve workforce integration is illustrated throughout the discussions of
      policies and resources required for workforce integration at national and
      organisational levels, conditions for positive group interactions and group
      cohesion in organisations. CONCLUSION: Our study reveals inadequate rules and
      resources used to recruit, classify and utilise immigrant nurses at national and
      healthcare organisational levels can become structural constraints on their
      adaptation to professional nursing practice and integration into the workforce in
      a host country. Learning from each other in multicultural teams and positive
      intergroup interaction in promoting intercultural understanding are enablers
      contributing to immigrant nurses' adaptation and workforce integration.

PMID- 24016599
TI  - The accuracy of adult limb radiograph interpretation by emergency nurse
      practitioners: A prospective comparative study.
AB  - BACKGROUND: One of the extensions to practice for the emergency nurse
      practitioner role is to appropriately order and interpret radiographs in the
      emergency department. OBJECTIVE: The aim of the study was to compare the accuracy
      in interpreting isolated adult limb radiographs between emergency nurse
      practitioners and emergency physicians. DESIGN: A prospective comparative study
      was undertaken. SETTING: Emergency department in a large metropolitan hospital.
      PARTICIPANTS: 200 adult patients with isolated limb injuries were consented.
      METHODS: Six emergency nurse practitioners and ten emergency physicians
      participated. One emergency physician and emergency nurse practitioner
      independently clinically assessed each patient, determined the need for
      radiograph and separately recorded their interpretation of the radiograph as
      either definite fracture, no fracture or possible fracture. A single consultant
      radiologist reviewed each radiograph and their interpretation was seen as the
      gold standard. The sensitivity and specificity of emergency physicians and
      emergency nurse practitioners were calculated. To measure the level of agreement
      between the two-clinician groups, the weighted Kappa statistic was used. RESULTS:
      The sensitivity for the emergency nurse practitioners was 91% and 88% for the
      emergency physicians. The specificity for the emergency nurse practitioners was
      85% and for the emergency physicians 91%. The weighted Kappa on the presence of a
      fracture between the emergency nurse practitioners and emergency physicians was
      0.83. CONCLUSIONS: This study validates the clinical and diagnostic skills of
      emergency nurse practitioners assessed in the interpretation of isolated adult
      limb injury radiographs.

PMID- 24016600
TI  - Pig farmers' perceptions, attitudes, influences and management of information in
      the decision-making process for disease control.
AB  - The objectives of this study were (1) to explore the factors involved in the
      decision-making process used by pig farmers for disease control and (2) to
      investigate pig farmers' attitudes and perceptions about different information
      sources relating to disease control. In 2011 a qualitative study involving 20
      face-to-face interviews with English pig farmers was conducted. The questionnaire
      was composed of three parts. The first part required farmers to identify two
      diseases they had experienced and which were difficult to recognize and/or
      control. They were asked to report how the disease problem was recognized, how
      the need for control was decided, and what affected the choice of control
      approach. For the latter, a structure related to the Theory of Planned Behaviour
      was used. Their verbal responses were classified as associated with: (1) attitude
      and beliefs, (2) subjective norms, or (3) perceived behavioural control (PBC). In
      the second part, five key sources of information for disease control (Defra,
      BPEX, research from academia, internet and veterinarians) and the factors related
      to barriers to knowledge were investigated. Interviews were recorded and
      transcribed. A qualitative analysis of the text of the interview transcripts was
      carried out using templates. Drivers for disease control were 'pig mortality',
      'feeling of entering in an economically critical situation', 'animal welfare' and
      'feeling of despair'. Veterinarians were perceived by several participating
      farmers as the most trusted information source on disease control. However, in
      particular non-sustainable situations, other producers, and especially
      experiences from abroad, seemed to considerably influence the farmers' decision
      making. 'Lack of knowledge', 'farm structure and management barriers' and
      'economic constrains' were identified in relation to PBC. Several negative
      themes, such as 'lack of communication', 'not knowing where to look', and
      'information bias' were associated with research from academia. This study
      identified a range of factors influencing the decision-making process for disease
      control by pig farmers. In addition, it highlighted the lack of awareness and
      difficult access of producers to current scientific research outputs. The factors
      identified should be considered when developing communication strategies to
      disseminate research findings and advice for disease control. 

PMID- 24016601
TI  - Tracking sulfur and phosphorus within single starch granules using synchrotron X
      ray microfluorescence mapping.
AB  - BACKGROUND: Native starch accumulates as granules containing two glucose
      polymers: amylose and amylopectin. Phosphate (0.2-0.5%) and proteins (0.1-0.7%)
      are also present in some starches. Phosphate groups play a major role in starch
      metabolism while granule-bound starch synthase 1 (GBSS1) which represents up to
      95% of the proteins bound to the granule is responsible for amylose biosynthesis.
      METHODS: Synchrotron micro-X-ray fluorescence (MUXRF) was used for the first time
      for high-resolution mapping of GBSS1 and phosphate groups based on the XRF signal
      of sulfur (S) and phosphorus (P), respectively. Wild-type starches were studied
      as well as their related mutants lacking GBSS1 or starch-phosphorylating enzyme.
      RESULTS: Wild-type potato and maize starch exhibited high level of
      phosphorylation and high content of sulfur respectively when compared to mutant
      potato starch lacking glucan water dikinase (GWD) and mutant maize starch lacking
      GBSS1. Phosphate groups are mostly present at the periphery of wild-type potato
      starch granules, and spread all over the granule in the amylose-free mutant. P
      and S XRF were also measured within single small starch granules from Arabidopsis
      or Chlamydomonas not exceeding 3-5MUm in diameter. CONCLUSIONS: Imaging GBSS1 (by
      S mapping) in potato starch sections showed that the antisense technique
      suppresses the expression of GBSS1 during biosynthesis. P mapping confirmed that
      amylose is mostly present in the center of the granule, which had been suggested
      before. GENERAL SIGNIFICANCE: MUXRF is a potentially powerful technique to
      analyze the minor constituents of starch and understand starch
      structure/properties or biosynthesis by the use of selected genetic backgrounds.

PMID- 24016604
TI  - Structural features of the G-protein/GPCR interactions.
AB  - BACKGROUND: The details of the functional interaction between G proteins and the
      G protein coupled receptors (GPCRs) have long been subjected to extensive
      investigations with structural and functional assays and a large number of
      computational studies. SCOPE OF REVIEW: The nature and sites of interaction in
      the G-protein/GPCR complexes, and the specificities of these interactions
      selecting coupling partners among the large number of families of GPCRs and G
      protein forms, are still poorly defined. MAJOR CONCLUSIONS: Many of the contact
      sites between the two proteins in specific complexes have been identified, but
      the three dimensional molecular architecture of a receptor-Galpha interface is
      only known for one pair. Consequently, many fundamental questions regarding this
      macromolecular assembly and its mechanism remain unanswered. GENERAL
      SIGNIFICANCE: In the context of current structural data we review the structural
      details of the interfaces and recognition sites in complexes of sub-family A
      GPCRs with cognate G-proteins, with special emphasis on the consequences of
      activation on GPCR structure, the prevalence of preassembled GPCR/G-protein
      complexes, the key structural determinants for selective coupling and the
      possible involvement of GPCR oligomerization in this process.

PMID- 24016603
TI  - Identification and active site analysis of the 1-aminocyclopropane-1-carboxylic
      acid oxidase catalysing the synthesis of ethylene in Agaricus bisporus.
AB  - BACKGROUND: 1-Aminocyclopropane-1-carboxylate oxidase (ACO) is a key enzyme that
      catalyses the final step in the biosynthesis of the plant hormone ethylene.
      Recently, the first ACO homologue gene was isolated in Agaricus bisporus, whereas
      information concerning the nature of the ethylene-forming activity of this
      mushroom ACO is currently lacking. METHODS: Recombinant ACO from A. bisporus (Ab
      ACO) was purified and characterised for the first time. Molecular modelling
      combined with site-directed mutagenesis and kinetic and spectral analysis were
      used to investigate the property of Ab-ACO. RESULTS: Ab-ACO has eight amino acid
      residues that are conserved in the Fe (II) ascorbate family of dioxygenases,
      including four catalytic residues in the active site, but Ab-ACO lacks a key
      residue, S289. In comparison to plant ACOs, Ab-ACO requires ACC and Fe (II) but
      does not require ascorbate. In addition, Ab-ACO had relatively low activity and
      was completely dependent on bicarbonate, which could be ascribed to the
      replacement of S289 by G289. Moreover, the ferrous ion could induce a change in
      the tertiary, but not the secondary, structure of Ab-ACO. CONCLUSIONS: These
      results provide crucial experimental support for the ability of Ab-ACO to
      catalyse ethylene formation in a similar manner to that of plant ACOs, but there
      are differences between the biochemical and catalytic characteristics of Ab-ACO
      and plant ACOs. GENERAL SIGNIFICANCE: This work enhances the understanding of the
      ethylene biosynthesis pathways in fungi and could promote profound physiological
      research of the role of ethylene in the regulation of mushroom growth and
      development.

PMID- 24016602
TI  - A mutation associated with centronuclear myopathy enhances the size and stability
      of dynamin 2 complexes in cells.
AB  - BACKGROUND: Dynamin 2 (Dyn2) is a ~100kDa GTPase that assembles around the necks
      of nascent endocytic and Golgi vesicles and catalyzes membrane scission.
      Mutations in Dyn2 that cause centronuclear myopathy (CNM) have been shown to
      stabilize Dyn2 polymers against GTP-dependent disassembly in vitro. Precisely
      timed regulation of assembly and disassembly is believed to be critical for Dyn2
      function in membrane vesiculation, and the CNM mutations interfere with this
      regulation by shifting the equilibrium toward the assembled state. METHODS: In
      this study we use two fluorescence fluctuation spectroscopy (FFS) approaches to
      show that a CNM mutant form of Dyn2 also has a greater propensity to self
      assemble in the cytosol and on the plasma membrane of living cells. RESULTS:
      Results obtained using brightness analysis indicate that unassembled wild-type
      Dyn2 is predominantly tetrameric in the cytosol, although different oligomeric
      species are observed, depending on the concentration of expressed protein. In
      contrast, an R369W mutant identified in CNM patients forms higher-order oligomers
      at concentrations above 1MUM. Investigation of Dyn2-R369W by Total Internal
      Reflection Fluorescence (TIRF) FFS reveals that this mutant forms larger and more
      stable clathrin-containing structures on the plasma membrane than wild-type Dyn2.
      CONCLUSIONS AND GENERAL SIGNIFICANCE: These observations may explain defects in
      membrane trafficking reported in CNM patient cells and in heterologous systems
      expressing CNM-associated Dyn2 mutants.

PMID- 24016605
TI  - MicroRNAs as regulators of mitochondrial function: role in cancer suppression.
AB  - BACKGROUND: Mitochondria, essential to the cell homeostasis maintenance, are
      central to the intrinsic apoptotic pathway and their dysfunction is associated
      with multiple diseases. Recent research documents that microRNAs (miRNAs)
      regulate important signalling pathways in mitochondria, and many of these miRNAs
      are deregulated in various diseases including cancers. SCOPE OF REVIEW: In this
      review, we summarise the role of miRNAs in the regulation of the mitochondrial
      bioenergetics/function, and discuss the role of miRNAs modulating the various
      metabolic pathways resulting in tumour suppression and their possible therapeutic
      applications. MAJOR CONCLUSIONS: MiRNAs have recently emerged as key regulators
      of metabolism and can affect mitochondria by modulating mitochondrial proteins
      coded by nuclear genes. They were also found in mitochondria. Reprogramming of
      the energy metabolism has been postulated as a major feature of cancer.
      Modulation of miRNAs levels may provide a new therapeutic approach for the
      treatment of mitochondria-related pathologies, including neoplastic diseases.
      GENERAL SIGNIFICANCE: The elucidation of the role of miRNAs in the regulation of
      mitochondrial activity/bioenergetics will deepen our understanding of the
      molecular aspects of various aspects of cell biology associated with the genesis
      and progression of neoplastic diseases. Eventually, this knowledge may promote
      the development of innovative pharmacological interventions. This article is part
      of a Special Issue entitled Frontiers of Mitochondrial Research.

PMID- 24016606
TI  - Dielectric characterization of costal cartilage chondrocytes.
AB  - BACKGROUND: Chondrocytes respond to biomechanical and bioelectrochemical stimuli
      by secreting appropriate extracellular matrix proteins that enable the tissue to
      withstand the large forces it experiences. Although biomechanical aspects of
      cartilage are well described, little is known of the bioelectrochemical
      responses. The focus of this study is to identify bioelectrical characteristics
      of human costal cartilage cells using dielectric spectroscopy. METHODS:
      Dielectric spectroscopy allows non-invasive probing of biological cells. An in
      house computer program is developed to extract dielectric properties of human
      costal cartilage cells from raw cell suspension impedance data measured by a
      microfluidic device. The dielectric properties of chondrocytes are compared with
      other cell types in order to comparatively assess the electrical nature of
      chondrocytes. RESULTS: The results suggest that electrical cell membrane
      characteristics of chondrocyte cells are close to cardiomyoblast cells, cells
      known to possess an array of active ion channels. The blocking effect of the non
      specific ion channel blocker gadolinium is tested on chondrocytes with a
      significant reduction in both membrane capacitance and conductance. CONCLUSIONS:
      We have utilized a microfluidic chamber to mimic biomechanical events through
      changes in bioelectrochemistry and described the dielectric properties of
      chondrocytes to be closer to cells derived from electrically excitably tissues.
      GENERAL SIGNIFICANCE: The study describes dielectric characterization of human
      costal chondrocyte cells using physical tools, where results and methodology can
      be used to identify potential anomalies in bioelectrochemical responses that may
      lead to cartilage disorders.

PMID- 24016607
TI  - The expression and localization of leptin and its receptor in goat ovarian
      follicles.
AB  - Leptin, a hormone that was originally identified in adipocytes, has been
      implicated in the regulation of ovarian folliculogenesis through endocrine,
      autocrine and/or paracrine mechanisms. The aim of this study was to investigate
      the expression patterns of leptin (LEP) and its receptor (LEPRb) in different
      types of ovarian follicular cells from goats. In small follicles, the expression
      levels of LEP were higher (P<0.001) in granulosa cells than in theca cells,
      cumulus cells and oocytes. The expression of LEP in granulosa cells was higher
      (P<0.001) in small follicles than in large follicles. In large follicles, the
      expression of LEPRb was higher (P<0.05) in granulosa cells than in theca cells,
      cumulus cells and oocytes. Higher expression (P<0.05) of LEPRb was detected in
      granulosa cells isolated from large follicles than in granulosa cells isolated
      from small follicles. Immunohistochemical analyses revealed the presence of the
      LEP and LEPR proteins in follicles at all stages of development. The most intense
      staining for LEP and LEPR was observed in the cytoplasm of oocytes and the
      surrounding granulosa cells. In conclusion, it was demonstrated that leptin and
      its receptor are expressed at both the mRNA and protein levels in goat ovarian
      follicles. Furthermore, the presence of a leptin signaling system in the caprine
      ovary suggests a potential regulatory role for leptin in follicular development
      and the maturation of goat oocytes. 

PMID- 24016608
TI  - HIV, leukemia, and new horizons in molecular therapy.
AB  - Cancer and human immunodeficiency virus (HIV) are both scary things to have in
      your body, but a new treatment is successfully using the latter against the
      former. Recent news reports, among others in the New York Times, talked about
      this new cure for leukemia by using HIV. This mini-review puts this news in
      perspective and provides a broader view as there appear to be several areas where
      clinical research on HIV and leukemia seem to connect. The topics covered range
      from antiviral gene therapy approaches using HIV-based lentiviral vectors to the
      risk of leukemia induction by these integrating vectors, and from an anti
      leukemia transplantation strategy that turned out to provide a functional cure
      for HIV, to novel vaccination approaches. 

PMID- 24016609
TI  - Retinopathy of prematurity in southern Taiwan: a 10-year tertiary medical center
      study.
AB  - BACKGROUND/PURPOSE: Retinopathy of prematurity (ROP) is a leading cause of
      childhood blindness. This retrospective study investigated ROP, including
      incidence, demographic information,risk factors, treatments, and refractive
      outcomes, in southern Taiwan over a 10-year period. METHODS: The authors
      retrieved the National Cheng Kung University Hospital database between the years
      2000 and 2009 for newborns with a gestational age less than 32 weeks and/or with
      a birth weight less than 1500 g who had been screened for ROP. We recorded sex,
      birth weight, gestational age, in-hospital versus out-of-hospital birth, paternal
      and maternal ages, whether there were multiple gestations, parity, Apgar scores,
      length of hospital stay, risk factors, presence and severity of ROP and whether
      it was treated, and refraction at the last visit. Regression analyses were
      performed to identify risk factors for ROP. RESULTS: A total of 503 live births
      were included. ROP was identified in 190 (37.8%) and met criteria for treatment
      in 59 (11.7%).ROP was diagnosed as stage 1, 2, 3, 4, and 5 in 61 (12.1%), 36
      (7.2%), 81 (16.1%), 11 (2.2%), and 1 (0.2%) infant, respectively. Lower birth
      weight and younger gestational age were risk factors for greater severity of ROP
      (p < 0.001). Of the 167 with extremely low birth weight (<1000 g), 118 (70.7%)
      had ROP and 49 (29.3%) required treatment. On univariate analysis, low birth
      weight, younger gestational age, and risk factors such as respiratory distress
      syndrome, chronic lung disease, patent ductus arteriosus, surfactant usage,
      indomethacin usage, sepsis, upper gastrointestinal bleeding, blood transfusion,
      and necrotizing enterocolitis were associated with ROP. Multivariate logistic
      regression analysis showed that only lower birth weight was a significant and
      independent risk factor for ROP. Myopia (76%)and anisometropia (28%)were common
      in advanced ROP. CONCLUSION: Low birth weight is a major risk factor for ROP.
      Infants with extremely low birth weight had a higher risk of severe ROP. Common
      ocular sequelae of advanced ROP were myopia and anisometropia.

PMID- 24016610
TI  - Attenuating brain inflammation, ischemia, and oxidative damage by hyperbaric
      oxygen in diabetic rats after heat stroke.
AB  - BACKGROUND/PURPOSE: Alternating hypothalamic-pituitary-adrenal axis mechanisms
      would lead to multiple organs dysfunction or failure. Herein, we attempt to
      assess whether hypothalamic inflammation and ischemic and oxidative damage that
      occurred during heatstroke (HS) can be affected by hyperbaric oxygen (HBO2)
      therapy in streptozotocin-induced diabetic rats. METHODS: In this study,
      anesthetized diabetic rats, immediately after the onset of HS, were divided into
      two major groups and given the normobaric air (21% O2 at 1.0 atmospheres
      absolute) or HBO2 (100% O2 at 2.0 atmospheres absolute). HS was induced by
      exposing the animals to heat stress (43 degrees C). Another group of anesthetized
      diabetic rats was kept at normothermic state and used as controls. RESULTS: The
      survival time values for the HBO2-treated HS-diabetic rats increased form the
      control values of 78-82 minutes to new values of 184-208 minutes. HBO2 therapy
      caused a reduction of HS-induced cellular ischemia (e.g., increased cellular
      levels of glutamate and lactate/pyruvate ratio), hypoxia (e.g., decreased
      cellular levels of PO2), inflammation (e.g., increased cellular levels of
      interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, and
      myeloperoxidase), and oxidative damage (e.g., increased values of nitric oxide,
      2,3-dihydroxybenzoic acid, glycerol, and neuronal damage score) in the
      hypothalamus of the diabetic rats. CONCLUSION: Our results suggest that, in
      diabetic animals, HBO2 therapy may improve outcomes of HS in part by reducing
      heat-induced activated inflammation and ischemic and oxidative damage in the
      hypothalamus and other brain regions.

PMID- 24016611
TI  - Effect of intraoperative neuromonitoring on recurrent laryngeal nerve palsy rates
      after thyroid surgery--a meta-analysis.
AB  - BACKGROUND/PURPOSE: Though intraoperative nerve monitoring (IONM) during thyroid
      surgery has gained universal acceptance for localizing and identifying the
      recurrent laryngeal nerve (RLN), its role in reducing the rate of RLN injury
      remains controversial. In order to assess the effect of IONM during thyroid
      surgery, its value in reducing the incidence of RLN palsy was systematically
      evaluated. METHODS: Studies were evaluated for inclusion in this analysis by
      researching PubMed, Embase, the Cochrane Central Register of Controlled Trials,
      and the references of included studies. The initial screening of article titles
      and abstracts was independently performed by five reviewers based on the research
      protocol criteria. Each article was then read in detail and discussed before
      inclusion in the meta-analysis. Data were independently extracted, including the
      level of evidence, number of at-risk nerves, allocation method, baseline
      equivalence between groups, definitions of transient and permanent vocal fold
      palsy, systematic application of electrodes, etc. The meta-analysis was then
      performed. Odds ratios were pooled using a random effects model. RESULTS: Five
      randomized clinical trials and 12 comparative trials evaluating 36,487 at-risk
      nerves were included. Statistically significant differences in terms of total
      recurrent laryngeal nerve palsy (3.37% with intraoperative nerve monitoring
      [IONM] vs. 3.76% without IONM [OR: 0.74; 95% confidence interval [CI]: 0.59
      0.92]) and transient recurrent laryngeal nerve palsy (2.56% with IONM vs. 2.71%
      without IONM [OR: 0.80; 95% CI: 0.65-0.99]) were identified. The persistent
      incidence of recurrent laryngeal nerve palsy was 0.78% for IONM versus 0.96% for
      nerve identification alone (OR: 0.80; 95% CI: 0.62-1.03). CONCLUSION: Based on
      this meta-analysis, statistically significant differences were determined in
      terms of the incidences of total and transient recurrent laryngeal nerve palsy
      after using IONM versus recurrent laryngeal nerve identification alone during
      thyroidectomy. However, no statistically significant differences were identified
      regarding the incidence of persistent recurrent laryngeal nerve palsy between
      groups.

PMID- 24016612
TI  - Clinical applicability of quantitative nailfold capillaroscopy in differential
      diagnosis of connective tissue diseases with Raynaud's phenomenon.
AB  - BACKGROUND/PURPOSE: Nailfold capillaroscopy is a useful tool to distinguish
      primary from secondary Raynaud's phenomenon (RP) by examining the morphology of
      nailfold capillaries but its role in disease diagnosis is not clearly
      established. The purpose of this study was to evaluate the roles of quantitative
      nailfold capillaroscopy in differential diagnosis of connective tissue diseases
      (CTDs) with RP. METHODS: The data between the year 2005 and 2009 were retrieved
      from the nailfold capillaroscopic database of National Taiwan University Hospital
      (NTUH). Only the data from the patients with RP were analyzed. The criteria for
      interpretation of capillaroscopic findings were predefined. The final diagnoses
      of the patients were based on the American College of Rheumatology classification
      criteria for individual diseases, independent of nailfold capillaroscopic
      findings. The sensitivity and the specificity of each capillaroscopic pattern to
      the diseases were determined. RESULTS: The data from a total of 67 patients were
      qualified for the current study. We found the sensitivity and specificity of
      scleroderma pattern for systemic sclerosis (SSc) were 89.47% and 80%, and the
      specificity of the early, active, and late scleroderma patterns for SSc reached
      87.5%, 97.5%, and 95%, respectively. The sensitivity/specificity of systemic
      lupus erythematosus (SLE) pattern for SLE and polymyositis/dermatomyositis
      (PM/DM) pattern for PM/DM were 33.33%/95.45% and 60%/96.3%, respectively. The
      sensitivity/specificity of mixed connective tissue disease (MCTD) pattern for
      MCTD were 20%/100%. CONCLUSION: The nailfold capillaroscopic (NC) patterns may be
      useful in the differential diagnosis of CTDs with RP. The NC patterns for SSc and
      PM/DM are both sensitive and specific to the diseases, while the SLE and MCTD
      patterns exhibit high specificity but relatively low sensitivity.

PMID- 24016613
TI  - Clear cell carcinoma of female urethral diverticulum--a case report.
AB  - Primary malignancies of female urethral diverticulum are rare. A well-documented
      female patient with primary clear cell carcinoma of the urethral diverticulum is
      presented here. A 65-year-old woman presented with frequency and voiding
      difficulty for 2 months. Physical examination showed a 4-cm mass protruding from
      anterior vaginal wall. Intravenous urography, magnetic resonance imaging, and
      cystoscopy showed a polypoid mass in urethral diverticulum. She then underwent
      anterior exenteration with ileal conduit diversion and urethrectomy. Pathology
      confirmed the diagnosis of clear cell adenocarcinoma with bladder neck invasion.
      She had no disease recurrence at 2-year follow-up. Careful clinical examination
      and image studies are helpful in making the preoperative diagnosis for the rare
      disease. Early radical surgery can achieve better survival. 

PMID- 24016614
TI  - Prevalence of carbapenemase-producing Enterobacteriaceae and its impact on
      clinical outcomes at a teaching hospital in Taiwan.
AB  - Among 15,174 non-duplicated Enterobacteriaceae isolates, the prevalence of
      carbapenem-nonsusceptible Enterobacteriaceae (CNSE) was about 2.5% at a teaching
      hospital in Taiwan during 2010. Among 117 available isolates of CNSE, 8.6%
      carried genes encoding carbapenemases. Tigecycline and colistin were the most
      active agents against carbapenemase-producing and non-producing isolates.
      Patients infected with CNSE had an all-cause in-hospital mortality of 37.3%, and
      mortality was similar for infections from carbapenemase producers and non
      producers (14-day mortality rates: 22.2% and 21.5%; 30-day mortality rates: 22.2%
      and 32.3%, respectively). Continuous surveillance of CNSE is recommended in
      Taiwan.

PMID- 24016615
TI  - Tuberculous otitis media without lung involvement and the risk of airborne
      transmission.

PMID- 24016616
TI  - Isolated cardiac sarcoidosis: case experience in heart transplantation.

PMID- 24016617
TI  - Percutaneous correction of congenital overlapping fifth toe in paediatric
      patients.
AB  - The various available surgical methods for correcting congenital overlapping
      fifth toe deformity consistently require a skin plasty step, which can result in
      complications (necrosis, tight scar, unbecoming appearance). Here, we describe a
      percutaneous technique involving extensor tenotomy combined with release of the
      dorso-medial capsule and ligaments. No skin plasty is required. Percutaneous
      osteotomy of the first phalanx can be performed if needed. From 2006 to 2010, we
      used this technique in 16 patients (27 toes) with a mean age of 12.6years (range,
      6-17years). Mean follow-up at last evaluation was 2.1 years. Osteotomy of the
      first phalanx was performed for 13 toes. The outcome was very good for 21 toes
      and good for six toes. No relapses or complications were recorded. This simple
      and safe technique deserves consideration in children with congenital overlapping
      fifth toe.

PMID- 24016619
TI  - Endocrine emergencies in pregnancy.
AB  - Endocrine emergencies in pregnancy are rare and are more likely to occur in the
      absence of good obstetric care. Serious thyroid and diabetes related events in
      pregnancy are more common because of their higher prevalence in the normal
      population. Pituitary complications in pregnancy are now relatively rare. A high
      index of suspicion is needed for early diagnosis, and medical treatment is
      directed primarily at maintaining maternal hemodynamic stability. A close liaison
      between an endocrinologist, maternal-fetal specialist and intensivist is critical
      in optimising both maternal and fetal outcomes.

PMID- 24016618
TI  - Glucocorticoid receptor antagonism as a novel therapy for triple-negative breast
      cancer.
AB  - PURPOSE: Triple-negative breast cancer (TNBC) accounts for 10% to 20% of newly
      diagnosed invasive breast cancer. Finding effective targets for chemotherapy
      resistant TNBC has proven difficult in part because of TNBC's molecular
      heterogeneity. We have previously reported that likely because of the
      antiapoptotic activity of glucocorticoid receptor (GR) in estrogen receptor (ER)
      negative breast epithelial and cancer cells, high GR expression/activity in early
      stage TNBC significantly correlates with chemotherapy resistance and increased
      recurrence. We hypothesized that pretreatment with mifepristone, a GR antagonist,
      would potentiate the efficacy of chemotherapy in GR+ TNBCs by inhibiting the
      antiapoptotic signaling pathways of GR and increasing the cytotoxic efficiency of
      chemotherapy. EXPERIMENTAL DESIGN: TNBC cell apoptosis was examined in the
      context of physiologic glucocorticoid concentrations, chemotherapy, and/or
      pharmacologic concentrations of mifepristone. We used high-throughput live
      microscopy with continuous recording to measure apoptotic cells stained with a
      fluorescent dye and Western blot analysis to detect caspase-3 and PARP cleavage.
      The effect of mifepristone on GR-mediated gene expression was also measured. TNBC
      xenograft studies were performed in female severe combined immunodeficient (SCID)
      mice and tumors were measured following treatment with vehicle, paclitaxel, or
      mifepristone/paclitaxel. RESULTS: We found that although mifepristone treatment
      alone had no significant effect on TNBC cell viability or clonogenicity in the
      absence of chemotherapy, the addition of mifepristone to dexamethasone/paclitaxel
      treatment significantly increased cytotoxicity and caspase-3/PARP cleavage.
      Mifepristone also antagonized GR-induced SGK1 and MKP1/DUSP1 gene expression
      while significantly augmenting paclitaxel-induced GR+ MDA-MB-231 xenograft tumor
      shrinkage in vivo. CONCLUSIONS: These results suggest that mifepristone
      pretreatment could be a useful strategy for increasing tumor cell apoptosis in
      chemotherapy-resistant GR+ TNBC.

PMID- 24016620
TI  - Recovery of atrioventricular block following steroid therapy in patients with
      cardiac sarcoidosis.
AB  - BACKGROUND: Atrioventricular (AV) block is one of the main clinical
      manifestations in patients with cardiac sarcoidosis (CS). Although steroid
      therapy is considered to be effective for AV block, the efficacy has not been
      demonstrated in detail. METHODS AND RESULTS: Fifteen CS patients presenting with
      advanced or complete AV block were retrospectively investigated. All patients
      were treated with 30mg/day of prednisone after device implantation, which was
      tapered to a maintenance dosage of 5-10mg/day. During a mean follow-up of 7.1
      years, AV block resolved to normal conduction or first-degree AV block in 7
      patients (recovery group). The improvement was driven within the first week of
      steroid therapy in 4 patients, while 3 patients showed late recovery of AV
      conduction. The remaining 8 patients were classified as the non-recovery group.
      The recovery group showed a higher left ventricular ejection fraction (69.4+/
      8.9% versus 44.1+/-19.3%, p=0.029) and higher prevalence of advanced AV block
      (87.5% versus 28.6%, p=0.040) compared with those of the non-recovery group. In
      patients with the recovery group, there was no late recurrence of AV block during
      the follow-up period. CONCLUSIONS: Early initiation of steroid therapy may be
      effective for AV block, and steroid therapy before device implantation is a
      possible therapeutic strategy for some selected patients.

PMID- 24016621
TI  - Association between obstructive sleep apnea and premature supraventricular
      contractions.
AB  - OBJECTIVE: The exact association between obstructive sleep apnea (OSA) and
      premature supraventricular contractions (PSVCs) has not been established.
      METHODS: We prospectively performed polysomnography together with 24-hour Holter
      electrocardiography in 431 patients who were clinically suspected of having OSA
      and examined the association between OSA severity and PSVCs during wakefulness
      and sleep. The patients were classified into 4 groups according to the apnea
      hypopnea index (AHI) quartiles (Q1=patients with AHI<13.8, Q2=those with
      13.8<=AHI<28.8, Q3=those with 28.8<=AHI<48.1, Q4=those with AHI>=48.1). RESULTS:
      The number of PSVCs/hour during sleep differed significantly among the 4 groups,
      but the number of PSVCs/hour during wakefulness did not. The prevalence of
      PSVC>=5/hour during sleep was significantly higher in Q4 (21.0%) than the other 3
      groups (Q1, 9.0%; Q2, 8.0%; Q3, 6.0%; all p<0.05 for Q4), but the prevalence of
      PSVC>=5/hour during wakefulness did not differ among the 4 groups. A multivariate
      logistic regression analysis showed that the highest AHI quartile was
      significantly associated with PSVC>=5/hour during sleep (odds ratio 3.04, 95%
      confidence interval 1.44-6.42, p=0.004). CONCLUSIONS: Severe OSA can cause PSVCs
      during sleep, but its effect appears not to be strong. Further studies are needed
      to clarify the clinical significance of this small but significant increase in
      PSVCs during sleep in severe OSA patients.

PMID- 24016622
TI  - Myocardial bridging is associated with coronary atherosclerosis in the segment
      proximal to the site of bridging.
AB  - BACKGROUND: Myocardial bridging is a common finding on multi-detector computed
      tomography (MDCT). The segment proximal to a myocardial bridge is frequently
      atherosclerotic, although the tunneled segment is spared. This study aimed to
      investigate whether myocardial bridging identified by MDCT is an independent risk
      factor for coronary atherosclerosis. METHODS AND RESULTS: Patients (n=188) with
      suspected coronary disease underwent MDCT using a 40-detector or 64-detector
      instrument. We reviewed the baseline characteristics (age, body mass index,
      smoking history, presence of hypertension, dyslipidemia, and diabetes mellitus)
      and the results of MDCT angiography. Two radiologists evaluated the coronary
      artery for myocardial bridging and coronary atherosclerosis and made a diagnosis
      by consensus. Significant independent risk factors for coronary atherosclerosis
      were investigated by multivariate logistic regression analysis. We identified 50
      bridges in the middle segment of the left anterior descending artery (LAD). There
      were no patients with significant stenosis in the tunneled segment. Multivariate
      analysis showed that age, diabetes mellitus, and myocardial bridging in the mid
      LAD were significantly associated with coronary atherosclerosis in the proximal
      LAD (p<0.05). Age, diabetes mellitus, and the absence of myocardial bridging in
      the mid-LAD were significantly associated with coronary atherosclerosis in the
      mid-LAD (p<0.05). CONCLUSION: The segment proximal to a segment with myocardial
      bridging is frequently involved in atherosclerosis, although the tunneled segment
      is spared. Myocardial bridging in the mid-LAD is an independent risk factor for
      coronary atherosclerosis in the proximal LAD.

PMID- 24016624
TI  - Uremia-related oxidative stress in leukocytes is not triggered by beta2
      microglobulin.
AB  - BACKGROUND: Chronic kidney disease (CKD) is characterized by low-grade
      inflammation and increased risk for cardiovascular disease. The interest in beta2
      microglobulin (B2M) as a marker for cardiovascular outcome with and without CKD
      has grown. Clinical studies suggested that B2M could be involved in the
      pathogenesis of vascular disease, for which chronic leukocyte activation is a
      pathogenic factor. We investigated whether B2M is proinflammatory by inducing
      oxidative burst in leukocytes. METHODS: Oxidative burst was measured at baseline
      and after stimulation with N-formyl-methionine-leucine-phenylalanine (fMLP),
      Escherichia coli, or phorbol-12-myristate-acetate (PMA) in the whole blood of
      healthy volunteers in the absence (saline) and presence of human B2M (hB2M; 10
      and 50 mg/L) versus uremic whole blood. Because of suspicion of contamination,
      hB2M was dialyzed for purification and purified B2M (dB2M) and dialysates were
      tested in the burst test. As a comparator, reactive oxygen species (ROS) in
      response to lipopolysaccharide (LPS) was measured. RESULTS: Unpurified hB2M
      strongly enhanced ROS in monocytes and granulocytes after E. coli and PMA and
      moderately after fMLP stimulation compared with control (P < .01) and uremia (P <
      .01) whereas at baseline hB2M only induced ROS in granulocytes (P < .05). After
      purification, dB2M no longer increased burst activity, suggesting that
      contamination was responsible for the initial effect. An endotoxin concentration
      of less than 1.5 EU/mL, as observed in hB2M, could not induce oxidative stress.
      CONCLUSION: This study suggests that B2M, a traditional marker for middle
      molecule retention and a novel marker for cardiovascular outcome, may not by
      itself cause vascular damage by influencing inflammatory response due to
      induction of leukocyte free radical production. However, an effect on other cell
      types involved cannot be excluded. Our data further reveal that this type of
      research might be skewed by non-LPS contaminants, and that care should be taken
      to exclude this bias.

PMID- 24016623
TI  - Association of triglyceride-rich lipoproteins-related markers and low-density
      lipoprotein heterogeneity with cardiovascular risk: effectiveness of
      polyacrylamide-gel electrophoresis as a method of determining low-density
      lipoprotein particle size.
AB  - BACKGROUND: Despite well-controlled low-density lipoprotein cholesterol (LDL-C),
      hypertriglyceridemia is an independent predictor of coronary events. We
      investigated the risk of atherosclerotic cardiovascular disease through examining
      the relation between triglyceride (TG) metabolism and LDL-heterogeneity as
      assessed by polyacrylamide-gel electrophoresis (PAGE). METHODS AND RESULTS:
      Estimated LDL-particle size [relative LDL migration (LDL-Rm value)] measured by
      PAGE with the LipoPhor system (Joko, Tokyo, Japan) was evaluated in 645
      consecutive patients with one additional risk factor for atherosclerotic
      cardiovascular disease.Multivariate regression analysis after adjustments for
      traditional risk factors revealed an elevated triglyceride-rich lipoproteins
      (TRLs)-related markers [TG, remnant-like particle cholesterol (RLP-C), very LDL
      (VLDL) fraction, apolipoprotein (apo) C-II, and apo C-III] level to be an
      independent predictor of smaller-size LDL-particle size, both in the overall
      population, and in a subset of patients with serum LDL-C <100 mg/dL. Even among
      the patients with LDL-C levels <100 mg/dL, the serum levels of atherogenic lipid
      markers in those with a LDL-Rm value >=0.40, suggesting the presence of large
      amounts of small-dense LDL and upper limit (mean+2 standard deviation) in this
      population, were significantly higher than in those with a LDL-Rm value <0.40.
      Moreover, the serum levels of TRLs-related markers showed high accurate area
      under the receiver-operating characteristic curve (TG, 0.896; RLP-C, 0.875; VLDL
      fraction, 0.803; apo C-II, 0.778; and apo C-III, 0.804, respectively) in terms of
      evaluation of the indicators of LDL-Rm value >=0.40. CONCLUSION: To further
      reduce the risk of atherosclerotic cardiovascular disease, it may be of
      particular importance to pay attention not only to the quantitative change in the
      serum LDL-C, but also TG-metabolism associated with LDL-heterogeneity. Combined
      evaluation of TRLs-related markers and LDL-Rm value may be useful for assessing
      the risk of atherosclerotic cardiovascular disease.

PMID- 24016625
TI  - Disposition of fipronil in rats.
AB  - In the scientific literature, little attention has been paid to the disposition
      of fipronil, a phenyl pyrazole insecticide. In this study, the tissue
      distribution, the metabolic fate, and the elimination of fipronil was
      investigated in rats using radiolabeled fipronil. When a single oral dose of
      (14)C-fipronil (10 mg kg(-1) b.w.) was given to rats, the proportion of dose
      eliminated in urine and feces 72 h after dosing was ca 4% for each route. At the
      end of the experiment the highest levels of radioactivity were found in adipose
      tissue and adrenals. The main part of the radioactivity present in investigated
      tissues (adipose tissue, adrenals, liver, kidney, testes) was due to fipronil
      sulfone. Five additional metabolites, isolated from urine were characterized by
      LC-MS/MS. Most of them are formed by the loss of the trifluoromethylsulphinyl
      group and subsequent hydroxylation and/or conjugation to glucuronic acid or
      sulfate. In conclusion, the retention of the metabolite fipronil sulfone in
      tissues following fipronil administration raises the question of the potential
      toxicity of this insecticide.

PMID- 24016626
TI  - LC-ICP-MS analysis of arsenic compounds in dominant seaweeds from the Thermaikos
      Gulf (Northern Aegean Sea, Greece).
AB  - The content of total arsenic and arsenic compounds in the dominant seaweed
      species in the Thermaikos Gulf, Northern Aegean Sea was determined in samples
      collected in different seasons. Total arsenic was determined by acid digestion
      followed by ICP-MS. Arsenic speciation was analyzed by water extraction followed
      by LC-ICP-MS. Total arsenic concentrations in the seaweeds ranged from 1.39 to
      55.0 mg kg(-1). Cystoseira species and Codium fragile showed the highest total As
      contents, while Ulva species (U. intestinalis, U. rigida,U. fasciata) had the
      lowest Arsenosugars, the most common arsenic species in seaweeds, were found in
      all samples, and glycerol-arsenosugar was the most common form; however,
      phosphate-arsenosugar and sulfate-arsenosugar were also present. Inorganic
      arsenic was measured in seven algae species and detected in another. Arsenate was
      the most abundant species in Cystoseira barbata (27.0 mg kg(-1)). Arsenobetaine
      was measured in only one sample. Methylated arsenic species were measured at very
      low concentrations. The information should contribute to further understanding
      the presence of arsenic compounds in dominant seaweeds from the Thermaikos Gulf.

PMID- 24016627
TI  - Is the bone tissue of ring-billed gulls breeding in a pollution hotspot in the
      St. Lawrence River, Canada, impacted by halogenated flame retardant exposure?
AB  - Bone metabolism is a tightly regulated process that controls bone remodeling and
      repair in addition to maintaining circulating calcium and phosphate levels. It
      has been shown that certain organohalogen contaminants may adversely impact bone
      tissue metabolism and structure in wildlife species. However, exceedingly few
      studies have addressed the bone-related effects of organohalogen exposure in
      birds. The objective of the present study was to investigate the associations
      between markers of bone metabolism and structural integrity, and concentrations
      of established and current-use halogenated flame retardants (FRs) in ring-billed
      gulls (Larus delawarensis) nesting in a known FR hotspot area in the St. Lawrence
      River (Montreal, Canada). Bone metabolism was assessed using plasma calcium and
      inorganic phosphate levels, and alkaline phophatase activity, while bone (tarsus;
      trabecular and cortical sections) structure quality was examined using the
      percentage of bone tissue comprised in the total bone volume (Bv/Tv) and bone
      mineral density (BMD). Bv/Tv and BMD of the tarsus tended (not significant) to be
      positively associated with circulating calcium levels in male ring-billed gulls.
      Moreover, concentrations of FRs in male bird liver (brominated diphenyl ether
      (BDE)-154, -183, -201, and -209) and plasma (BDE-209) were negatively correlated
      with trabecular and cortical BMD of the tarsus. These correlative associations
      may suggest light demineralization of bone tissue associated with FR exposure in
      male ring-billed gulls. Present findings provide some evidence that bone (tarsus)
      metabolism and mineral composition may be impacted in high FR-exposed (mainly to
      PBDEs) ring-billed gulls breeding in the highly urbanized Montreal region. 

PMID- 24016628
TI  - Determination of indicator polychlorinated biphenyls (PCBs) by gas chromatography
      electron capture detector.
AB  - An effective method for determination of indicator polychlorinated biphenyls
      (PCBs) has been validated using gas chromatography (GC) equipped with electron
      capture detector (ECD). The GC-ECD method was validated by determining the linear
      range (working range) for determination of the compounds, minimum detectable
      quantities (MDQ), the precision and accuracy of the method for the analysis of
      the compounds. MDQ obtained for the compounds ranges from 0.0005 to 0.002 ng.
      Indeed the method was found to be more sensitive as the number of chlorine atoms
      attached to the biphenyl increases. The precision and accuracy of the GC method
      validated ranges from 2.4% to 14.5% and -7.0% to 14.6% respectively. Coefficient
      of variation associated with the repeatability of the retention times and
      corresponding peak areas was found to be 0.0001-0.0007 for the retention times
      and 0.0014-0.059 for the peak areas. Percentage recoveries for the compounds were
      in the range of 95.7-101.0%. The validated method was then applied to determine
      levels of indicator PCBs in sediments sampled from eleven sampling points along
      the Lake Bosuntwi in Ghana and the highest PCB load of 19.17 ng g(-1) was
      recorded at Pipie No. 2. PCB 52 and PCB 101 were found to be the most ubiquitous
      indicator PCBs in the study area, both with 90.91% occurrence.

PMID- 24016629
TI  - The loss of multidisciplinary primary healthcare teams is bad for patient care.

PMID- 24016630
TI  - Anthropogenic contaminants in Indo-Pacific humpback and Australian snubfin
      dolphins from the central and southern Great Barrier Reef.
AB  - We present the first evidence of accumulation of organochlorine compounds (DDTs,
      PCBs, HCB) and polycyclic aromatic hydrocarbons (PAHs) in Indo-Pacific humpback
      and Australian snubfin dolphins from the central and southern Great Barrier Reef.
      These dolphins are considered by the Great Barrier Marine Park Authority to be
      high priority species for management. Analyses of biopsy samples, collected from
      free ranging individuals, showed PAHs levels comparable to those reported from
      highly industrialized countries. DDTs and HCB were found at low levels, while in
      some individuals, PCBs were above thresholds over which immunosuppression and
      reproductive anomalies occur. These results highlight the need for ongoing
      monitoring of these and other contaminants, and their potential adverse effects
      on dolphins and other marine fauna. This is particularly important given the
      current strategic assessment of the Great Barrier Reef World Heritage Area being
      undertaken by the Australian Government and the Queensland Government. 

PMID- 24016632
TI  - [Acta Medica Portuguesa and the Cochrane Collaboration].

PMID- 24016631
TI  - Outcomes of children after esophagogastroduodenoscopy for chronic abdominal pain.
AB  - BACKGROUND & AIMS: Chronic abdominal pain is the most common indication for
      esophagogastroduodenoscopy (EGD) in children. However, little is known about the
      accuracy of EGD-based diagnosis or the outcomes of the patients who undergo this
      procedure. We examined the diagnostic yield of EGD and short-term outcomes of
      children who underwent this procedure for chronic abdominal pain. METHODS: We
      conducted a prospective study of 290 children (4-18 years old; mean age, 11.9 +/-
      3.5 years; 93 girls) who underwent EGD for the primary indication of chronic
      abdominal pain (216 with at least 1 alarm feature) at a US pediatric
      gastroenterology referral center. We collected data on demographic features (age,
      sex), clinical characteristics (alarm features, Rome III criteria), and EGD
      results for each patient. All subjects with diagnostic lesions were followed for
      at least 1 year after EGD to determine short-term outcomes. RESULTS: Overall, EGD
      provided an accurate diagnosis for 109 children (38%). Diagnoses included
      esophagitis (21.0%), eosinophilic gastroenteritis (4.1%), eosinophilic
      esophagitis (3.8%), Helicobacter pylori infection (2.0%), celiac disease (0.6%),
      and Crohn's disease (0.4%). Short-term outcomes were available for 81% of
      patients with diagnostic findings, and medical therapy was effective in
      approximately 67% of these children. CONCLUSIONS: EGD is valuable for the
      diagnosis of children with abdominal pain, with a 38% diagnostic yield. EGD
      identified disorders for which medical therapy was effective in 67% of children
      during the year after diagnosis.

PMID- 24016633
TI  - [Regarding "end of life in neonatology: palliative care integration"].

PMID- 24016634
TI  - Dementia: not only Alzheimer's disease, an eye on frontotemporal dementia.

PMID- 24016635
TI  - [Abstract of Cochrane review].

PMID- 24016636
TI  - The health and wealth of Portugal.

PMID- 24016637
TI  - Biobanco-IMM, Lisbon Academic Medical Centre: a case study.

PMID- 24016638
TI  - [Mortality from diabetes in Portugal].

PMID- 24016639
TI  - [End of life in neonatology: palliative care integration].
AB  - BACKGROUND: Today the limitation of therapeutic effort and the neonatal
      palliative care are extremely important and had been increasingly done by several
      countries. Nevertheless, in Portugal, studies and guidelines regarding end of
      life attitudes are still a shortage. MATERIAL AND METHODS: We analyzed 49 files
      in a retrospective review of neonatal deaths between 2010 and 2012; the results
      were compared with those from a previous study made in the same NICU that
      included the neonatal deaths of 1992-1995 and 2002-2005. RESULTS: The results
      show that congenital anomalies were the cause of death for 57.1% newborns,
      extreme prematurity for 18.4% and 16.3% died with infection. Regarding to the
      mode of death, 57.1% of newborns died after cardiopulmonary resuscitation
      failure, 20.4% after withholding treatment and 22.4% of deaths followed therapy
      withdrawal. Differences were found between the three groups classified according
      to the 'mode of death', length of stay and parental presence during death.
      Therapeutic limitation practices and palliative care were reported in 28.6% of
      the files and a Do-Not-Resuscitate Order was included in 16.3%. The former two
      increased during the three periods analyzed. The use of a neonatal pain scale,
      opioids and sedatives administration, parental presence during death, clinical
      meetings with neonatologists, interdisciplinary meetings and psychological
      support for parents also increased. CONCLUSION: This study shows a trend towards
      an increase in therapeutic limitation practices and palliative care in this NICU
      in the last three decades. However, there is still a lot to do regarding the
      clinical research, medical education and ethical discussion.

PMID- 24016640
TI  - [Epidemiological study of place of death in Portugal in 2010 and comparison with
      the preferences of the Portuguese population].
AB  - INTRODUCTION: In the context of a pronounced population ageing and rising
      mortality due to chronic illnesses, this national epidemiological study compares
      the places where people die with population preferences. MATERIAL AND METHODS:
      Data on numbers of deaths in 2010 by gender, age group, region of residence NUTS
      II and place of death (hospital/clinic, domicile and other) of people with 16+
      years old were provided by the Portuguese Statistics Institute. Data on
      population preferences for place of death were obtained in 2010 in the PRISMA
      telephone survey. The distribution of deaths by place of death is compared with
      population preferences, according to independent variables, using descriptive and
      inferential analysis. RESULTS: There were 105 471 deaths in Portugal in 2010.
      From these, 61.7% occurred at hospitals/clinics and 29.6% at the domicile. Of the
      1 286 residents in Portugal that participated in the PRISMA survey, 51.2% chose
      home as preferred place of death, 35.7% chose a palliative care unit, 8.9% the
      hospital and 2.2% a nursing or residential home. DISCUSSION AND CONCLUSION: There
      is a substantial gap between the reality and population preferences for place of
      death in Portugal. To better meet these preferences, it is a national priority to
      develop home palliative care services that prevent the rise of hospital deaths
      and that support death at home, with quality and whenever wished. It is
      recommended changing the coding of place of death in Portuguese death
      certificates, with inclusion of the options 'palliative care unit' and 'nursing
      or residential home', once citizens' preferences clearly differentiate these
      places.

PMID- 24016641
TI  - [MAST and AUDIT. Evaluation of psychometric characteristics in patients with
      alcohol dependence].
AB  - INTRODUCTION/OBJECTIVE: To evaluate the correlation between scores on the MAST
      and AUDIT in patients hospitalized for detoxification from alcohol dependence and
      consider if the intensity of those scores reflect the severity of dependence and
      problems related to alcohol use. MATERIAL AND METHODS: Correlational study.
      Patients admitted for the first time for alcohol dependence treatment. In
      addition to a structured interview, the MAST and the AUDIT, SADD was used to
      assess the degree of alcohol dependence and the APQ to assess the problems
      related to alcohol consumption. RESULTS: The internal consistency (Cronbach's
      alpha) of the MAST was 0.77 and the AUDIT was 0.73. The correlation between the
      two instruments was moderate (R = 0.497, p < 0.001). Both presented moderate and
      significant correlation (p < 0.001) with the APQ and SADD. The set of items from
      AUDIT directed towards dependence led to a higher correlation with SADD than with
      APQ, the reverse being true with the set of items belonging to the dimension
      problems / adverse consequences. The two instruments have low correlation with
      the volume of alcohol consumption measured in g/d. CONCLUSION: Both the MAST and
      the AUDIT have a total score that reflects the severity of dependence and alcohol
      induced disorders. In clinical populations, these instruments can be used as a
      continuous variable to record quantitatively the magnitude of the problems. The
      AUDIT, relatively to the MAST, has the advantage of representing a smaller number
      of items, making it easier to answer and quote. The AUDIT also has the advantage
      of presenting sets of items belonging to three dimensions (quantity / frequency,
      dependency, problems / adverse effects) that can be analyzed separately, allowing
      for the characterization and further specification of the situations under study.

PMID- 24016642
TI  - Toxic epidermal necrolysis: the experience of Coimbra's burn unit.
AB  - INTRODUCTION: Toxic Epidermal Necrolysis is a drug-induced life-threatening
      systemic disease, characterized by extensive dermoepidermal detachment and
      mucositis. At least 95% of cases are believed to be drug-induced. SCORTEN is a
      scoring system used to stratify severity and predict mortality. Treatment demands
      immediate withdrawal of the causative drug and early transfer to a burn centre
      for specific and intensive care. MATERIAL AND METHODS: Authors have performed a
      retrospective study of 21 consecutive patients with SJS/ Toxic Epidermal
      Necrolysis admitted in the Burn Centre of Coimbra's University Hospital, between
      January 1999 and December 2010, and have compared the actual mortality rate with
      that predicted by SCORTEN, in order to assess the predictive capacity of SCORTEN.
      Analysis of results and treatment options were conducted. Data were analysed in
      SPSS 17.0(r). RESULTS: Thirteen females (61.9%) and 8 males (38.1%) were treated,
      mean age 55.6 +/- 23.7 years and with a mean of 51% +/- 22.4% epidermal
      detachment. The overall observed mortality rate was 47.6% and the one predicted
      by SCORTEN 42.2%. Immediate withdrawal of the causative drug and early transfer
      of the patient to our burn centre were the basis of treatment. CONCLUSION: Toxic
      Epidermal Necrolysis pathophysiology remains to be clarified and no specific
      treatment has unequivocally proven to be effective. SCORTEN seems to be an
      accurate scoring system for estimation of mortality rate.

PMID- 24016643
TI  - [Surgical treatment of spinal tuberculosis: an orthopedic service experience].
AB  - INTRODUCTION: Tuberculosis is responsible for more than 40% of spine infections.
      While tuberculostatic chemotherapy remains the gold-standard treatment, surgical
      intervention is necessary only in specific cases. This paper reports the results
      of 33 patients with spine tuberculosis operated in our department in the last 15
      years. OBJECTIVE: Evaluate retrospectively patients with spine tuberculosis
      operated in the last 15 years - from 1996 to 2011; evaluate the surgical options,
      infection resolution results, deformity correction, functional results and
      outcome in cases of neurological injury. MATERIAL AND METHODS: Analysis of
      clinical and radiological assessments of patients diagnosed with spine
      tuberculosis and operated between 1996 and 2011. In this period 33 patients were
      operated with average age of 46.7 years; 17 patients had thoracic infection, 11
      patients lumbar infection and 5 thoraco-lumbar infection. Paravertebral abscess
      was identified in 26 cases with intracanal extension in 16 patients. Nine
      patients had neurological injury. The anterior surgical approach was used in
      seven cases, the posterior approach in 11 and anterior-posterior approach was
      preferred in 15 occasions. Antituberculous chemotherapy was maintained on average
      for 14 months, with mean follow up of 24 months. RESULTS: The infection was
      eradicated in all patients. Bone fusion was found in average at 10.6 months
      follow-up. The anterior approach did not produce correction of the initial
      deformity, while the posterior approach allowed average correction of 12.7
      degrees  and the anterior-posterior approach a mean correction of 8.7 degrees .
      Five patients with neurological injury experienced improvement of 2 or 3 levels
      in ASIA score. We also report complications in two cases where superficial wound
      infection was diagnosed. DISCUSSION AND CONCLUSION: Treatment with
      antituberculosis drugs is the first-line therapy in the treatment of tuberculous
      spondylodiscitis, while surgical treatment has specific indications. The surgical
      option, when indicated, allows deformity correction and bone fusion. The anterior
      posterior or only posterior surgical approach is preferred in this context. The
      complication rate was not significant despite the introduction of osteosynthesis
      hardware.

PMID- 24016644
TI  - Psychiatry training towards a global future: trainees' perspective in Portugal.
AB  - INTRODUCTION: Psychiatry is influenced by society changes, so it should be
      permanently updating itself, foreseeing future behaviours and pathologies. This
      study aims to describe psychiatry trainee's opinion in Portugal concerning their
      training and the modifications they would want to witness in the near future.
      MATERIAL AND METHODS: A structured questionnaire of 26 questions was developed by
      the Portuguese Association of Psychiatry Trainees and sent via email. RESULTS:
      The percentage of responses was 41.5%. The majority of the trainees were
      satisfied with their formation. However, some changes were pointed out concerning
      obligatory and optional placements. Most trainees claimed psychotherapy should be
      included in their training, along with an easier access to investigational
      procedures and clinical training opportunities abroad. DISCUSSION AND CONCLUSION:
      This detailed perspective can facilitate the transformation of the curricula
      throughout Portugal and Europe, allowing the improvement of psychiatry training,
      as well as the enhancement of mental health care.

PMID- 24016645
TI  - [Juvenile Pompe disease: retrospective clinical study].
AB  - INTRODUCTION: Pompe disease or glycogen storage disease type II is an autosomal
      recessive disorder due to acid maltase deficiency. It is a rare disease with a
      prevalence of 1/40.000 in the dutch and african-american populations and 1/46000
      in the australian population. There are three forms of clinical presentation
      (infantile-onset, childhood-onset and adult-onset), although the disease presents
      as a continuum of clinical phenotypes. Enzyme replacement therapy is available in
      Portugal since 2006. MATERIALS AND METHODS: The clinical files of four patients
      (two sisters) were analyzed retrospectively. RESULTS: In all, disease presented
      in the second year of life and the time to diagnosis ranged from two to eleven
      years. At diagnosis, all presented myopathic features with a delay in motor
      skills achievement and two had myocardium hypertrophy. Clinical suspicion arose
      as the result of respiratory failure during infection in two patients. Plasma
      creatine kinase and aminotransferases levels were increased in all. All patients
      progressed to pulmonary restrictive syndrome with chronic respiratory failure.
      The diagnosis was based on reduced activity of acid maltase in fibroblasts: 0 to
      1.5% of the lower normal value. Muscle biopsy, performed in three patients,
      showed lysosomal glycogen accumulation. A c.1064T > C mutation in exon 6 of GAA
      (glucosidase-alpha-acid) gene was found in all patients, in homozygosity in one.
      In the sisters, it was associated to c.1666A > G and c.2065G > A mutations in
      exons 12 and 15, respectively and in the youngest patient, to c.380G > T mutation
      in exon 2. All patients started enzyme replacement therapy as soon as it became
      available, with good tolerance. The youngest patient died. The surviving patients
      maintain ventilatory support measures and physiotherapy. The oldest patient is
      wheelchair ridden and her sister keeps independent walking. The youngest uses a
      walking aid. CONCLUSIONS: Our cases are clinically included in the juvenile form
      of Pompe Disease. Pompe disease should be suspected in progressive myopathies at
      any age, especially those involving limb-girdle and respiratory muscles and in
      small infants with cardiomyopathy. High creatine kinase is a sensitive, although
      nonspecific, marker. Given the great variability of the genetic findings,
      demonstration of reduced activity of acid maltase (in leukocytes or other
      tissues) remains the diagnosis cornerstone of this rare disorder.

PMID- 24016646
TI  - [Evolution of residual risk for HIV, HCV and HBV, from 1999 to 2010, in blood
      donations of the Centro Hospitalar S. Joao, EPE, Porto, Portugal].
AB  - INTRODUCTION/OBJECTIVES: Monitoring the residual risk of transfusion-transmitted
      viral infections is important to evaluate the improvement achieved in the blood
      donation safety and to adopt policies to reduce risks. The present study
      calculates the incidence of the key infectious diseases, human immunodeficiency
      virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) as well as the
      residual risk of transfusion-transmitted viral infections, during twelve years,
      1999 through 2010. Data were analyzed over 3 periods of 4 years (1999-2002, 2003
      2006 and 2007-2010). The risk estimates were compared to those previously
      obtained for blood donations occurred between 1991 and 1998. MATERIAL AND
      METHODS: The study included 209 640 blood donations, from 42 634 regular,
      volunteers and unpaid donors. The residual risk of transfusion-transmitted
      infection per million donations was calculated, for each virus, through
      mathematical model "Incidence rate/window period", described by Schreiber et al.
      All donations were screened according to Portuguese legislation. In January 2001,
      the nucleic acid testing in minipool was implemented on all blood donations, for
      screening simultaneously HIV-1 and HCV ribonucleic acid (RNA) (Cobas Amplicor
      Ampliscreen-Roche(c)). This test was replaced, in January 2007, by the
      simultaneous screening of HBV deoxyribonucleic acid, HCV RNA and HIV-1/HIV-2 RNA,
      in minipool (Cobas Taqscreen MPX Test-Roche(c)). RESULTS: The residual risk of
      transmitting viral infections during the transfusion of blood components is very
      small and has declined over the years. After the implementation of the nucleic
      acid testing in minipool for the three viruses, the risk of giving blood during
      an infectious window period was estimated as follows: for human immunodeficiency
      virus, 1 in 1.67 million, for hepatitis C virus 1 in 3.33 million and for
      hepatitis B virus 1 in 526 000. CONCLUSIONS: During the 12 years under study, we
      found a decrease in residual risk for the three viruses, by a factor around five
      for human immunodeficiency virus and hepatitis B virus, and 32 for hepatitis C
      virus. If we compare the estimates previously calculated for 1991-1998 period to
      2007-2010 period (over 20 years), the decrease is still more relevant with a
      residual risk of human immunodeficiency virus, hepatitis B virus and hepatitis C
      virus respectively 19-fold, 6-fold and 54-fold lower.

PMID- 24016647
TI  - Differences in microbiological profile between community-acquired, healthcare
      associated and hospital-acquired infections.
AB  - INTRODUCTION: Microbiological profiles were analysed and compared for intra
      abdominal, urinary, respiratory and bloodstream infections according to place of
      acquisition: community-acquired, with a separate analysis of healthcare
      associated, and hospital-acquired. MATERIAL AND METHODS: Prospective cohort study
      performed at a university tertiary care hospital over 1 year. Inclusion criteria
      were meeting the Centers for Disease Control definition of intra-abdominal,
      urinary, respiratory and bloodstream infections. RESULTS: A total of 1035
      patients were included in the study. More than 25% of intra-abdominal infections
      were polymicrobial; multi-drug resistant gram-negatives were 38% in community
      acquired, 50% in healthcare-associated and 57% in hospital-acquired. E. coli was
      the most prevalent among urinary infections: 69% in community-acquired, 56% in
      healthcare-associated and 26% in hospital-acquired; ESBL producers' pathogens
      were 10% in healthcare-associated and 3% in community-acquired and hospital
      acquired. In respiratory infections Streptococcus pneumoniae was the most
      prevalent in community-acquired (54%) and MRSA in healthcare-associated (24%) and
      hospital-acquired (24%). A significant association was found between MRSA
      respiratory infection and hospitalization in the previous year (adjusted OR =
      6.3), previous instrumentation (adjusted OR = 4.3) and previous antibiotic
      therapy (adjusted OR = 5.7); no cases were documented among patients without risk
      factors. Hospital mortality rate was 10% in community-acquired, 14% in healthcare
      associated and 19% in hospital-acquired infection. DISCUSSION AND CONCLUSION:
      This study shows that healthcare-associated has a different microbiologic profile
      than those from community or hospital acquired for the four main focus of
      infection. Knowledge of this fact is important because the existing guidelines
      for community-acquired are not entirely applicable for this group of patients.

PMID- 24016648
TI  - [Health care associated multidrug-resistant bacteria in a pediatric hospital:
      five year experience].
AB  - INTRODUCTION: In recent years there has been an increase of infections caused by
      multidrug-resistant bacteria. Paediatric data are scarce, particularly at
      national level. AIMS: To analyse trends of health-care associated multidrug
      resistant bacteria infections in a paediatric hospital. MATERIAL AND METHODS: A
      retrospective incidence study was conducted in medical, surgical and intensive
      care wards in a level III paediatric hospital, from January 2005 to December
      2009. The studied multidrug-resistant bacteria were methicillin-resistant
      Staphylococcus aureus (MRSA), ESBL-producing bacilli, vancomycin-resistant
      Enterococcus spp, multidrug-resistant Pseudomonas aeruginosa (PA-MDR) and
      Acinetobacter baumannii resistant to carbapenems. Demographic, clinical and
      laboratory data, treatment and presence of risk factors for these infections were
      analysed. RESULTS: During the study period 106 multidrug-resistant bacteria were
      identified, related to 72 children, predominantly male (65.3%). The most
      frequently identified multidrug-resistant bacteria were MRSA (35.8%), PA-MDR
      (29.2%) and ESBL-producing bacilli (17.9%). Of the 106 multidrug-resistant
      bacteria, 45 (42.5%) were causing infection. During the study period the annual
      proportion of infections caused by multidrug-resistant bacteria went up from
      32.0% in 2006 to 55.6% in 2009 (p = 0.376). The overall incidence rate of
      infection was 0.400 per 1 000 hospitalization-days, corresponding to 0.274
      infections per 100 admissions, remaining stable over the five years. The most
      frequent infections were bloodstream (31.1%), intra-abdominal (20.0%), catheter
      related (17.8%) and skin and soft tissue (11.1%). All children had risk factors
      and the most frequently identified were previous antibiotic therapy and
      underlying chronic disease (> 90%). Six children (13.3%) died during
      hospitalisation. CONCLUSIONS: During the study period, there was an increase in
      the proportion of multidrug-resistant bacteria but with no statistical
      significance. The overall incidence rate of multidrug-resistant bacteria
      infection remained stable. MRSA were the most frequently identified bacteria,
      followed by PA-MDR and ESBL-producing bacilli. Bloodstream infections were the
      most frequent infections, followed by intra-abdominal and catheter-related. All
      children had risk factors, mainly previous antibiotic therapy and chronic
      disease.

PMID- 24016649
TI  - Clinical, genetic and neuropathological features of frontotemporal dementia: an
      update and guide.
AB  - INTRODUCTION: Frontotemporal Lobar Degeneration encompasses a group of
      heterogeneous disorders with shared behavioural and cognitive symptoms, as well
      as gross pathological features. The genetic underpinnings and histopathological
      aspects are quite diverse and form the basis of molecular classification, which
      is not easy to correlate with clinical findings and syndromes. Scientific
      research has brought to light an array of knowledge, often not easy to keep up
      with, especially in the last few years with regard to genetics and
      histopathology. MATERIAL AND METHODS: The authors have searched the published
      literature on this topic, chose relevant references, and extracted and
      systematized the data. RESULTS AND CONCLUSION: this manuscript presents an
      updated review of clinical, genetic and histopathological findings in
      Frontotemporal Lobar Degeneration, with special focus on behavioural variant
      Frontotemporal Dementia, the most common disorder. Current management is also
      reviewed, and genetic testing strategies are proposed by the authors for use in
      clinical practice. Public awareness on this group of disorders should be raised.

PMID- 24016650
TI  - [Mechanisms of resistance to BCR-ABL kinase inhibitors].
AB  - Since the introduction of imatinib mesylate for the treatment of chronic myeloid
      leukaemia, impressive clinical responses were observed in the majority of
      patients in chronic phase. However, not all patients experience an optimal
      response to imatinib mesylate or even to the more potent, second generation
      tyrosine kinase inhibitors. Furthermore, responses are not sustained in a number
      of patients, and it is yet unclear whether the inhibitors can be safely
      discontinued in patients who achieve long-term remission. The emergence of
      resistance to second generation tyrosine kinase inhibitors has become a
      significant problem that led to extensive studies on the causal mechanisms. This
      review will describe our current state of knowledge on why and how chronic
      myeloid leukaemia cells can develop resistance to second generation tyrosine
      kinase inhibitors. 

PMID- 24016651
TI  - [Off-label prescribing: scientific analysis taking the use of bevacizumab in
      ophthalmology as an example].
AB  - Off-label prescribing poses specific technical/scientific, professional and
      ethical problems. In this study we carry out a technical and scientific analysis
      of the off-label prescribing using a current, clinical and economically relevant
      example: the paradigmatic case of the use of bevacizumab in ophthalmologic
      pathologies for which it has no formal indication. We conducted a systematic
      review of the literature on the efficacy and safety of this drug, as well as
      ranibizumab - which has approved ophthalmologic indications, in order to
      qualitatively analyze the available evidence on the two interventions. This is a
      typical case for technical and scientific analysis of the off-label prescribing
      problems. According to the results of the systematic review, the use of
      bevacizumab in this context has in fact scientific evidence of appreciable size,
      including clinical trials head-to-head with ranibizumab. However, the identified
      safety issues raise the question of the use of this drug in ophthalmologic
      pathologies. The different players involved in the treatment decisions
      (physicians, patients and institutional decision makers) should be adequately
      informed about the existing evidence that supports off-label prescribing which,
      by definition, must always be on an exceptional basis and properly justified. 

PMID- 24016652
TI  - [Medical education and professionalism].
AB  - Is briefly analyzed the evolution that the objectives, strategies and models of
      medical education have had since their presentation and subsequent implementation
      of the famous model of Abraham Flexner, is now 103 years. Although globally
      accepted in their original pedagogical principles and instruments, that model
      does not have avoided the continuing dissatisfaction by the medical community and
      students and, most markedly in recent decades, the demanding of a most efficient
      health care by society, in general, and by patients in particular. In response to
      these ambitions, the medical community felt that it was essential to review the
      traditional criteria of medical professionalism, adapting them to a new paradigm
      of society and an appropriate and more efficient model of medical education. In
      this respect, are analyzed strategies and methodologies, apparently more suitable
      proposals for the inclusion of the principles and responsibilities of medical
      professionalism since the early period of pre-graduated medical education. It is
      assumed that the emphasis in teaching and practice of reflection throughout the
      course will have positive and lasting repercussions during active working life.
      However, the author believes that the success of the measures to be introduced in
      medical education programs to a new model of professionalism continues to depend,
      above all, of the humanistic and cognitive attributes of the students to be
      chosen, and the pedagogical quality, professional and academic of their teachers.

PMID- 24016653
TI  - [Diabetes and driving: evidence and recommendations].
AB  - In the last years there was an increasing concern about driving and some medical
      conditions. Diabetes is one of the diseases associated with road traffic
      accidents. This increased risk is associated with hypoglycemia and diabetes
      complications such as: retinopathy, cataracts and neuropathy. In order to avoid
      car crashes patients must follow some rules like carrying some sugar source in
      their vehicle, always measure blood glycemia before start driving, never begin an
      extended drive with blood glucose less than 90 mg/dl without prophylactic
      carbohydrate consumption, stop the vehicle as soon any of the symptoms of low
      blood glucose are experienced and measure and treat the blood glucose level. In
      Portugal there are new rules for diabetic drivers since January 2013. Group 1
      drivers are considerer unfit to drive if they have severe or recurrent
      hypoglycemia. Group 2 drivers need to present a medical report certificating they
      have good diabetes control, have not had any severe or recurrent hypoglycemia in
      the last twelve months and there aren't any other diabetes complications. 

PMID- 24016654
TI  - [Vital prognosis in advanced cancer patients: a systematic literature review].
AB  - Prognostication is a critical medical task for the adequacy of treatment and
      management of priorities and expectations of patients and families. In 2005, the
      European Association of Palliative Care (EAPC) published recommendations on the
      formulation of vital prognosis in advanced cancer patients. The aim of this study
      is to analyze the literature subsequent to this review and to update the
      presented recommendations. Using the same strategy of the EAPC group, we
      performed a systematic literature search in the electronic databases PubMed and
      Scopus, which included original studies in adults with advanced cancer, without
      tumor-directed treatment, with a median survival of less than 90 days. The
      articles were analyzed and classified according to the level of evidence by two
      independent reviewers. The 41 articles analyzed allowed to keep grade A
      recommendations for clinical estimation of survival and Palliative Prognostic
      score and now also for Palliative Prognostic Index, performance status, dyspnea,
      lymphopenia and lactate dehydrogenase. Recommendations regarding the use of C
      reactive protein, leukocytosis, azotemia, hypoalbuminemia and male gender as
      predictors reached grade B. To formulate the vital prognosis and to communicate
      it properly to the patient and family are core competencies of physicians,
      particularly of those who deal with end of life patients. The clinical impression
      combined with scientific evidence allows us to estimate more accurately the
      survival, allowing prioritizing and managing more appropriately the existing
      resources. 

PMID- 24016655
TI  - Osteoporosis: from bone biology to individual treatment decision.
AB  - INTRODUCTION: Osteoporosis is a bone metabolic disease with increasing prevalence
      in ageing societies. Herein we reviewed recent epidemiologic findings and their
      impact in the individual patient management. In addition we dissected the major
      disease mechanisms which have uncovered new potential therapeutic strategies.
      MATERIAL AND METHODS: Using MeSH terms (osteoporosis, epidemiology, Portugal,
      Europe, pathogenesis, osteoblasts, osteoclasts, osteocytes, immune system,
      obesity, therapy, randomized controlled trial, efficacy, safety) as keywords. We
      have reviewed original studies, reviews and position papers indexed in PubMed.
      RESULTS: Osteoporosis is increasingly prevalent, but recently an age-adjusted
      rate of fracture plateau was reached. A new fracture risk assessment tool was
      developed, FRAXTM, which integrates the contribution of clinical risk factors
      associated with fragility fractures. It can be used either independently or in
      combination with bone mineral density. Osteoporosis treatment is offered only to
      a fraction of the affected individuals. In addition, 40% of the patients
      receiving Osteoporosis medication had a previous fracture. Relevant safety issues
      of different drugs used in Osteoporosis have been detected in post-marketing
      experience. Finally, advances in the understanding of the molecular pathways
      involved in Osteoporosis led to the development of new drugs DISCUSSION AND
      CONCLUSION: Despite the existence of diagnostic tools and several effective
      treatments, Osteoporosis treatment is still offered only to a fraction of the
      affected individuals and mainly to a population with advanced disease. New and
      more effective treatments might change this scenario.

PMID- 24016656
TI  - Necrotizing Faciitis after shoulder mobilization and intra-articular infiltration
      with betametasone.
AB  - Necrotizing Fasciitis is a rapidly progressive, potentially fatal infection of
      superficial fasciae and subcutaneous tissue, usually resulting from an inciting
      trauma to the skin. Medical literature refers few cases of necrotizing fasciitis
      related to intra-articular infiltrations, that often lead to patients death. This
      report describes the clinical events on a 55 year-old diabetic patient who
      developed upper extremity Necrotizing Fasciitis, 18 days after shoulder
      mobilization and intra-articular infiltration, due to Staphylococcus epidermidis.
      An early surgical debridement was performed and antibiotherapy was established,
      resulting in a successful outcome, despite the functional disability. We point
      out, through this case, the possibility of intra-articular injections of drugs
      causing Necrotizing Fasciitis, especially in risk patients. 

PMID- 24016657
TI  - Localized Pigmented Villonodular Synovitis of the shoulder: a rare presentation
      of an uncommon pathology.
AB  - Pigmented Vilonodular Synovitis is a rare clinical entity characterized as a
      synovial membrane benign tumour, despite possible aggressive presentation with
      articular destruction. The localized variant is four times less frequent and the
      shoulder involvement is uncommon. We present the case of a Caucasian 59 year-old
      patient, who presented with left shoulder pain, of uncharacteristic quality, with
      local swelling and marked functional limitation of 1 month duration. Shoulder
      ultrasonography showed subacromial bursitis. An ultrasound-guided aspiration was
      performed: synovial fluid was citrine-colored and translucid. One month later,
      the patient maintained swelling, pain and functional impairment of the left
      shoulder. New shoulder ultrasound revealed exuberant subacromial bursitis, which
      was again aspirated using ultrasound guidance. The synovial fluid was haematic,
      without changes in the cell count or biochemical analysis and cultural exams. We
      performed an injection with 60 mg of hexacetonide triamcinolone. Two months later
      there was a relapse, with shoulder ultrasonography once more showing subacromial
      bursitis with extensive synovial membrane proliferation. Shoulder MRI revealed
      subacromial bursitis involving the anterior, posterior and medial recesses, with
      deltoid distension, but without tendinous or intra-articular involvement. In the
      interior of the bursa hypointense images in T2 were observed, suggesting the
      diagnosis of Pigmented Vilonodular Synovitis. The patient had surgical bursectomy
      with success and without complications. The histological exam of the operatory
      piece confirmed the imaging diagnosis. Pigmented Vilonodular Synovitis is
      uncommon, rarely affecting the shoulder in a localized variant. It is a diagnosis
      to be considered in shoulder pain, especially if associated with recurrent
      subacromial bursitis.

PMID- 24016658
TI  - [McArdle disease presenting with rhabdomyolisis and acute kidney injury].
AB  - McArdle disease typically presents in childhood or young adults with myalgia,
      exercise intolerance, cramps and myoglobinuria. Deficiency of myophosphorylase
      enzyme results in inability to degrade glycogen stores, causing glycogen
      accumulation in muscle tissue and energy deficit. Evolution with rhabdomiolysis
      may occur and can be complicated with acute kidney injury but rarely, in about
      11% of cases, is the initial disease manifestation. We report a case of McArdle
      Disease in a 38-year-old male patient. The disease went unrecognized despite
      previous symptoms (myalgia, exercise intolerance and single myoglobinuria
      episode) until an episode of rhabdomyolisis complicated with oliguric acute
      kidney injury requiring hemodialysis. The kidney biopsy showed evidence of acute
      tubular necrosis. Despite normalization of renal function, muscle lysis markers
      remained abnormal. Metabolic myopathy was suspected and a muscle biopsy was
      performed. It showed subsarcolemic glycogen deposition and absence of
      myophosphorylase activity. This case-report underlines the importance of
      considering metabolic myopathy in patients with acute kidney injury and severe
      rhabdomyolisis.

PMID- 24016659
TI  - Eccrine porocarcinoma: cytologic diagnosis by fine needle aspiration biopsy
      (FNAB).
AB  - INTRODUCTION: Eccrine porocarcinoma is an uncommon malignant adnexal tumor of the
      skin. Eccrine porocarcinoma is an adenocarcinoma of the eccrine sweat gland with
      a propensity to recur locally and gives metastases to regional lymph nodes. This
      paper presents a cytologic diagnosis by fine needle aspiration of an eccrine
      porocarcinoma along with histopathology and immunocyto-histochemistry. CASE
      REPORT: The cytologic findings of an eccrine porocarcinoma in a 76-year-old
      female and histologic features of the skin tumor are reported. Cytologically in
      fine needle aspiration biopsy, the tumor was characterized by atypical malignant
      cells with basophilic cytoplasm, hyperchromatic nuclei and prominent nucleoli.
      The cytologic diagnosis was confirmed by histology. CONCLUSIONS: The accurate
      preoperative diagnosis of eccrine porocarcinoma is crucial to developing a
      curative surgical plan. Fine needle aspiration cytology provides a convenient,
      safe and effective approach to solving a challenging differential diagnosis.

PMID- 24016660
TI  - [How to do an effective literature search? The use of Push and Pull strategies].
AB  - The availability of scientific information is growing exponentially. Healthcare
      professionals who wish to keep up-to-date with scientific literature and find the
      best information should spend their time finding resources that summarize the
      best available evidence. This manuscript aims to provide bibliographic research
      knowledge and skills, to contribute to an increase in the use of e-learning, to
      "Push and Pull" correct information and, in other words, to indicate how to deal
      with information overload. 

PMID- 24016661
TI  - [Epiploic appendagitis: a diagnosis often forgotten].

PMID- 24016662
TI  - [Cutaneous larva migrans].

PMID- 24016663
TI  - [The goal].

PMID- 24016666
TI  - Induction of amino acid transporters expression by endurance exercise in rat
      skeletal muscle.
AB  - We here investigated whether an acute bout of endurance exercise would induce the
      expression of amino acid transporters that regulate leucine transport across
      plasma and lysosomal membranes in rat skeletal muscle. Rats ran on a motor-driven
      treadmill at a speed of 28 m/min for 90 min. Immediately after the exercise, we
      observed that expression of mRNAs encoding L-type amino acid transporter 1 (LAT1)
      and CD98 was induced in the gastrocnemius, soleus, and extensor digitorum longus
      (EDL) muscles. Sodium-coupled neutral amino acid transporter 2 (SNAT2) mRNA was
      also induced by the exercise in those three muscles. Expression of proton
      assisted amino acid transporter 1 (PAT1) mRNA was slightly but not significantly
      induced by a single bout of exercise in soleus and EDL muscles. Exercise-induced
      mRNA expression of these amino acid transporters appeared to be attenuated by
      repeated bouts of the exercise. These results suggested that the expression of
      amino acid transporters for leucine may be induced in response to an increase in
      the requirement for this amino acid in the cells of working skeletal muscles.

PMID- 24016667
TI  - Mob as tumor suppressor is regulated by bantam microRNA through a feedback loop
      for tissue growth control.
AB  - The evolutionarily conserved Hippo signaling pathway plays an important role in
      regulating normal development as well as tumorigenesis in animals. How this
      growth-inhibitory signaling is maintained at an appropriate level through
      feedback mechanisms is less understood. In this report, we show that bantam
      microRNA functions to increase the level of the Mob as tumor suppressor protein
      Mats, a core component of the Hippo pathway, but does not regulate mats at the
      transcript level. Genetic analysis also supports that bantam plays a positive
      role in regulating mats function for tissue growth control. Our data support a
      model that bantam up-regulates Mats expression through an unidentified factor
      that may control Mats stability.

PMID- 24016668
TI  - Visualizing the effect of tumor microenvironments on radiation-induced cell
      kinetics in multicellular spheroids consisting of HeLa cells.
AB  - In this study, we visualized the effect of tumor microenvironments on radiation
      induced tumor cell kinetics. For this purpose, we utilized a multicellular
      spheroid model, with a diameter of ~500 MUm, consisting of HeLa cells expressing
      the fluorescent ubiquitination-based cell-cycle indicator (Fucci). In live
      spheroids, a confocal laser scanning microscope allowed us to clearly monitor
      cell kinetics at depths of up to 60 MUm. Surprisingly, a remarkable prolongation
      of G2 arrest was observed in the outer region of the spheroid relative to
      monolayer-cultured cells. Scale, an aqueous reagent that renders tissues
      optically transparent, allowed visualization deeper inside spheroids. About 16 h
      after irradiation, a red fluorescent cell fraction, presumably a quiescent G0
      cell fraction, became distinct from the outer fraction consisting of
      proliferating cells, most of which exhibited green fluorescence indicative of G2
      arrest. Thereafter, the red cell fraction began to emit green fluorescence and
      remained in prolonged G2 arrest. Thus, for the first time, we visualized the
      prolongation of radiation-induced G2 arrest in spheroids and the differences in
      cell kinetics between the outer and inner fractions.

PMID- 24016669
TI  - Regeneration of chronic tympanic membrane perforation using 3D collagen with
      topical umbilical cord serum.
AB  - Chronic tympanic membrane (TM) perforation is one of the most common otology
      complications. Current surgical management of TM perforation includes
      myringoplasty and tympanoplasty. The purpose of this study was to evaluate the
      efficacy and feasibility of three dimensional (3D) porous collagen scaffolds with
      topically applied human umbilical cord serum (UCS) for the regeneration of
      chronic TM perforation in guinea pigs. To achieve this goal, we fabricated porous
      3D collagen scaffolds (avg. strut diameter of 236 +/- 51 MUm, avg. pore size of
      382 +/- 67 MUm, and a porosity of 96%) by using a 3 axis robot dispensing and low
      temperature plate systems. Guinea pigs were used in a model of chronic TM
      perforation. In the experimental group (n=10), 3D collagen scaffold was placed on
      the perforation and topically applied of UCS every other day for a period of 8
      days. The control group ears (n=10) were treated with paper discs and phosphate
      buffered saline (PBS) only using the same regimen. Healing time, acoustic
      mechanical properties, and morphological analysis were performed by otoendoscopy,
      auditory brainstem response (ABR), single-point laser Doppler vibrometer (LDV),
      optical coherence tomography (OCT), and light microscopic evaluation. The closure
      of the TM perforation was achieved in 100% of the experimental group vs. 43% of
      the control group, and this difference was statistically significant (p=0.034).
      The ABR threshold at all frequencies of the experimental group was significantly
      recovered to the normal level compared to the control group. TM vibration
      velocity in the experimental group recovered similar to the normal control level.
      The difference is very small and they are not statistically significant below 1
      kHz (p=0.074). By OCT and light microscopic examination, regenerated TM of the
      experimental group showed thickened fibrous and mucosal layer. In contrast, the
      control group showed absence of fibrous layer like a dimeric TM.

PMID- 24016670
TI  - Truth relative to aortic overriding.

PMID- 24016672
TI  - Twin reunions: the science behind the fascination.

PMID- 24016671
TI  - Understanding the physical activity promotion behaviours of podiatrists: a
      qualitative study.
AB  - BACKGROUND: Health professionals are encouraged to play a part in reducing the
      health risks of physical inactivity. Little is known of the physical activity
      promotion practice behaviours of podiatrists. METHODS: We performed 20 semi
      structured interviews with purposefully selected podiatrists to explore their
      physical activity promotion attitudes, beliefs, knowledge and practice.
      Transcribed interviews were coded using an iterative thematic approach to
      identify major themes and salient beliefs. RESULTS: Overall, the participants had
      a positive attitude to physical activity promotion, considering it a normal part
      of their role. They saw their role as giving information, encouraging activity
      and making recommendations, however in practice they were less inclined to follow
      up on recommendations, monitor activity levels or document the process. Their
      approach was generally opportunistic, informal and unstructured and the content
      of assessment and promotion dependent upon the presenting patient's condition.
      Advice tended to be tailored to the patient's capabilities and interests. They
      considered there are opportunities to promote physical activity during regular
      consultations, however, were more likely to do so in patients with chronic
      diseases such as diabetes. Main barriers to physical activity promotion included
      unreceptive and unmotivated patients as well as a lack of time, skills and
      resources. CONCLUSIONS: Physical activity promotion appears feasible in podiatry
      practice in terms of opportunity and acceptability to practitioners, but there is
      scope for improvement. Strategies to improve promotion need to consider the major
      issues, barriers and opportunities as well as provide a more structured approach
      to physical activity promotion by podiatrists.

PMID- 24016673
TI  - Stereotactic body radiotherapy (SBRT) in central non-small cell lung cancer
      (NSCLC): solid evidence or "no-go"?

PMID- 24016674
TI  - Postoperative high-dose pelvic radiotherapy for N+ prostate cancer: toxicity and
      matched case comparison with postoperative prostate bed-only radiotherapy.
AB  - PURPOSE: To report on toxicity of postoperative high-dose whole-pelvis
      radiotherapy (WPRT) with androgen deprivation therapy for lymph node metastasized
      (N1) prostate cancer (PC). To perform a matched-case analysis to compare this
      toxicity profile to postoperative prostate bed-only radiotherapy (PBRT).
      MATERIALS AND METHODS: Forty-eight N1-PC patients were referred for WPRT and 239
      node-negative patients for PBRT. Patients were matched 1:1 according to pre
      treatment demographics, symptoms, treatment and tumor characteristics. Mean dose
      to the prostate bed was 75Gy (WPRT-PBRT) and 54Gy to the elective nodes (WPRT) in
      36 or 37 fractions. End points are genito-urinary (GU) and gastro-intestinal (GI)
      toxicity. RESULTS: After WPRT, 35% developed grade 2 (G2) and 4% G3 acute GU
      toxicity. Acute GI toxicity developed in 42% (G2). Late GU toxicity developed in
      36% (G2) and 7% (G3). One patient had G4 incontinence. Recuperation occurred in
      59%. Late GI toxicity developed in 25% (G2) with 100% recuperation. Incidence of
      acute and late GI toxicity was higher following WPRT compared to PBRT (p?0.041).
      GU toxicity was similar. With WPRT mean dose to bladder and rectosigmoid were
      higher. CONCLUSIONS: Postoperative high-dose WPRT comes at the cost of a
      temporary increase in G2. GI toxicity compared to PBRT because larger volumes of
      rectosigmoid are irradiated.

PMID- 24016675
TI  - Feasibility of proton beam therapy for reirradiation of locoregionally recurrent
      non-small cell lung cancer.
AB  - BACKGROUND AND PURPOSE: Options are limited for patients with intrathoracic
      recurrence of non-small cell lung cancer (NSCLC) who previously received
      radiation. We report our 5-year experience with the toxicity and efficacy of
      proton beam therapy (PBT) for reirradiation. MATERIALS AND METHODS: Thirty-three
      patients underwent PBT reirradiation for intrathoracic recurrent NSCLC at a
      single institution. All patients had had RT for NSCLC (median initial dose 63 Gy
      in 33 fractions), with median interval to reirradiation of 36 months. Median
      reirradiation dose was 66 Gy (RBE) in 32 fractions. Toxicity was scored with
      CTCAE v4.0, and survival outcomes were estimated using Kaplan-Meier. RESULTS:
      Thirty-one patients (94%) completed reirradiation. At a median 11 months' follow
      up, 1-year rates of overall survival, progression-free survival, locoregional
      control, and distant metastasis-free survival were 47%, 28%, 54%, and 39%. Rates
      of severe (grade >=3) toxicity were 9% esophageal, 21% pulmonary; 1 patient had
      grade 4 esophagitis, and 2 had grade 4 pulmonary toxicity. Nine patients
      experienced a second in-field failure. CONCLUSIONS: PBT is an option for treating
      recurrent NSCLC. However, the rates of locoregional recurrence and distant
      metastasis are high and the potential for toxicity significant. The risks and
      benefits of PBT must be carefully weighed in each case.

PMID- 24016676
TI  - Cardiac 18F-fluorodeoxyglucose uptake on positron emission tomography after
      thoracic stereotactic body radiation therapy.
AB  - BACKGROUND AND PURPOSE: Previous studies have shown that increased cardiac uptake
      of (18)F-fluorodeoxyglucose (FDG) on positron emission tomography (PET) may be an
      indicator of myocardial injury after radiotherapy. We reviewed patients treated
      with thoracic stereotactic body radiation therapy (SBRT) and established
      correlations between SBRT dose and observed changes in cardiac FDG-PET uptake.
      MATERIAL AND METHODS: Retrospective analysis identified 39 patients that were
      treated with SBRT for lung tumors close to the heart. Patients were grouped
      according to whether or not they had changes in cardiac FDG-PET uptake within the
      planned SBRT field. RESULTS: At a median follow-up interval of 39 months (range,
      6-81 months), nine patients (23%) showed increased cardiac FDG uptake associated
      with the heart V20. Of the 19 patients who received 20 Gy to >=5 cm(3) of the
      heart, nine (47%) developed increased FDG uptake (vs. 0% for the 20 patients who
      received 20 Gy to <5 cm(3)) (P=0.0004), all within the 20-Gy isodose line.
      Patients with hypercholesterolemia prior to SBRT were also more likely to show
      increased cardiac FDG uptake (P=0.0190). CONCLUSION: Increased FDG uptake in the
      heart after SBRT was observed when the 20 Gy isodose line exceeded 5 cm(3) of the
      heart.

PMID- 24016677
TI  - Hypofractionated intensity-modulated arc therapy for lymph node metastasized
      prostate cancer: early late toxicity and 3-year clinical outcome.
AB  - BACKGROUND AND PURPOSE: For patients with N1 prostate cancer (PCa) aggressive
      local therapies can be advocated. We evaluated clinical outcome, gastro
      intestinal (GI) and genito-urinary (GU) toxicity after intensity modulated arc
      radiotherapy (IMAT)+androgen deprivation (AD) for N1 PCa. MATERIAL AND METHODS:
      Eighty patients with T1-4N1M0 PCa were treated with IMAT and 2-3years of AD. A
      median dose of 69.3Gy (normalized isoeffective dose at 2Gy per fraction: 80Gy
      [alpha/beta=3]) was prescribed in 25 fractions to the prostate. The pelvic lymph
      nodes received a minimal dose of 45Gy. A simultaneous integrated boost to 72Gy
      and 65Gy was delivered to the intraprostatic lesion and/or pathologically
      enlarged lymph nodes, respectively. GI and GU toxicity was scored using the
      RTOG/RILIT and RTOG-SOMA/LENT-CTC toxicity scoring system respectively. Three
      year actuarial risk of grade 2 and 3/4 GI-GU toxicity and biochemical and
      clinical relapse free survival (bRFS and cRFS) were calculated with Kaplan-Meier
      statistics. RESULTS: Median follow-up was 36months. Three-year actuarial risk for
      late grade 3 and 2 GI toxicity is 8% and 20%, respectively. Three-year actuarial
      risk for late grade 3-4 and 2 GU toxicity was 6% and 34%, respectively. Actuarial
      3-year bRFS and cRFS was 81% and 89%, respectively. Actuarial 3-year bRFS and
      cRFS was, respectively 26% and 32% lower for patients with cN1 disease when
      compared to patients with cN0 disease. CONCLUSION: IMAT for N1 PCa offers good
      clinical outcome with moderate toxicity. Patients with cN1 disease have poorer
      outcome.

PMID- 24016678
TI  - A novel method for assessing the 3-D orientation accuracy of inertial/magnetic
      sensors.
AB  - A novel method for assessing the accuracy of inertial/magnetic sensors is
      presented. The method, referred to as the "residual matrix" method, is
      advantageous because it decouples the sensor's error with respect to Earth's
      gravity vector (attitude residual error: pitch and roll) from the sensor's error
      with respect to magnetic north (heading residual error), while remaining
      insensitive to singularity problems when the second Euler rotation is close to +/
      90 degrees . As a demonstration, the accuracy of an inertial/magnetic sensor
      mounted to a participant's forearm was evaluated during a reaching task in a
      laboratory. Sensor orientation was measured internally (by the inertial/magnetic
      sensor) and externally using an optoelectronic measurement system with a marker
      cluster rigidly attached to the sensor's enclosure. Roll, pitch and heading
      residuals were calculated using the proposed novel method, as well as using a
      common orientation assessment method where the residuals are defined as the
      difference between the Euler angles measured by the inertial sensor and those
      measured by the optoelectronic system. Using the proposed residual matrix method,
      the roll and pitch residuals remained less than 1 degrees  and, as expected, no
      statistically significant difference between these two measures of attitude
      accuracy was found; the heading residuals were significantly larger than the
      attitude residuals but remained below 2 degrees . Using the direct Euler angle
      comparison method, the residuals were in general larger due to singularity
      issues, and the expected significant difference between inertial/magnetic sensor
      attitude and heading accuracy was not present. 

PMID- 24016679
TI  - Concurrent validity of the Microsoft Kinect for assessment of spatiotemporal gait
      variables.
AB  - Spatiotemporal characteristics of gait such as step time and length are often
      associated with overall physical function in clinical populations, but can be
      difficult, time consuming and obtrusive to measure. This study assessed the
      concurrent validity of overground walking spatiotemporal data recorded using a
      criterion reference - a marker-based three-dimensional motion analysis (3DMA)
      system - and a low-cost, markerless alternative, the automated skeleton tracking
      output from the Microsoft KinectTM (Kinect). Twenty-one healthy adults performed
      normal walking trials while being monitored using both systems. The outcome
      measures of gait speed, step length and time, stride length and time and peak
      foot swing velocity were derived using supervised automated analysis. To assess
      the agreement between the Kinect and 3DMA devices, Bland-Altman 95% bias and
      limits of agreement, percentage error, relative agreement (Pearson's correlation
      coefficients: r) overall agreement (concordance correlation coefficients: rc) and
      landmark location linearity as a function of distance from the sensor were
      determined. Gait speed, step length and stride length from the two devices
      possessed excellent agreement (r and rc values >0.90). Foot swing velocity
      possessed excellent relative (r=0.93) but only modest overall (rc=0.54)
      agreement. Step time (r=0.82 and rc=0.23) and stride time (r=0.69 and rc=0.14)
      possessed excellent and modest relative agreement respectively but poor overall
      agreement. Landmark location linearity was excellent (R(2)=0.991). This widely
      available, low-cost and portable system could provide clinicians with significant
      advantages for assessing some spatiotemporal gait parameters. However, caution
      must be taken when choosing outcome variables as some commonly reported variables
      cannot be accurately measured. 

PMID- 24016680
TI  - Intravoxel bone micromechanics for microCT-based finite element simulations.
AB  - While micro-FE simulations have become a standard tool in computational
      biomechanics, the choice of appropriate material properties is still a relevant
      topic, typically involving empirical grey value-to-elastic modulus relations. We
      here derive the voxel-specific volume fractions of mineral, collagen, and water,
      from tissue-independent bilinear relations between mineral and collagen content
      in extracellular bone tissue (J. Theor. Biol. 287: 115, 2011), and from the
      measured X-ray attenuation information quantified in terms of grey values. The
      aforementioned volume fractions enter a micromechanics representation of bone
      tissue, as to deliver voxel-specific stiffness tensors. In order to check the
      relevance of this strategy, we convert a micro Computer Tomograph of a mouse
      femur into a regular Finite Element mesh, apply forces related to the dead load
      of a standing mouse, and then compare simulation results based on voxel-specific
      heterogeneous elastic properties to results based on homogeneous elastic
      properties related to the spatial average over the solid bone matrix compartment,
      of the X-ray attenuation coefficients. The element-specific strain energy density
      illustrates that use of homogeneous elastic properties implies overestimation of
      the organ stiffness. Moreover, the simulation reveals large tensile normal
      stresses throughout the femur neck, which may explain the mouse femur neck's
      trabecular morphology being quite different from the human case, where the femur
      neck bears compressive forces and bending moments. 

PMID- 24016681
TI  - Characterizing asymmetry across the whole sit to stand movement in healthy
      participants.
AB  - Sit-to-stand transfer (STS) is a common yet critical prerequisite for many daily
      tasks. Literature conducted on healthy STS often assume the body to behave
      symmetrically across the left and right side; yet only a few studies have been
      conducted to investigate this supposition. These studies have focused on a single
      numerical indicator such as peak joint moment (JM) values to describe
      symmetricity; however, STS is a dynamic and time dependent movement. This study
      addresses the validity of peak value analyses through the introduction of a time
      based peak-offset measure and proposes two time-dependent techniques to further
      characterize asymmetry and assesses their feasibility in ten (10) healthy male
      participants. JM and joint power (JP) over the whole STS movement was determined
      using motion capture and inverse dynamics. Using a paired one-tailed t-test
      differences were found in the time at which the left and right side reached peak
      values in all lower extremity joints (p<0.05) with exception of the hip JM. Using
      a measure of JM and JP straight-difference it was determined that the ankle joint
      displayed the largest number of JM and JP development strategies of all the lower
      extremity joints. Finally, through numerical integration of the JM and JP data
      with respect to time, it was found that the longer one side spends dominating the
      movement, the larger the excess angular impulse and work that can be expected
      from that side. The results suggest that when analyzing STS movements, one must
      be aware of the potential asymmetry present even in healthy movements.
      Furthermore, a simple peak JM or JP analysis may not fully describe the extent of
      these asymmetries. 

PMID- 24016682
TI  - Median percent change: a robust alternative for assessing temporal trends.
AB  - A typical summary statistic for temporal trends is the average percent change
      (APC). The APC is estimated by using a generalized linear model, usually under
      the assumption of linearity on the logarithmic scale. A serious limitation of
      least-squares type estimators is their sensitivity to outliers. The goal of this
      study is twofold: firstly, we propose a robust and easy-to-compute measure of the
      temporal trend based on the median of the rates (median percent change - MPC),
      rather than their mean, under the hypothesis of constant relative change;
      secondly, we investigate the performance of several models for estimating the
      rate of change when some of the most common model assumptions are violated. We
      provide some guidance on the practices of the estimation of temporal trends when
      using different models under different circumstances. The robustness property of
      the median is assessed in a simulation study, which shows that the MPC provides
      strong reductions in estimation bias and variance in presence of outliers. We
      also demonstrate how a mathematical property of the median helps addressing the
      issue of zero counts when estimating trends on the log-scale. Finally, we
      analyzed an English cancer registration dataset to illustrate the proposed
      method. We believe that, as a good practice, both APC and MPC should be presented
      when sensitivity issues arise. 

PMID- 24016683
TI  - Spatio-temporal differences in perineuronal net expression in the mouse
      hippocampus, with reference to parvalbumin.
AB  - Perineuronal net (PNN) is a specialized aggregate of the extracellular matrix,
      which is considered to be involved in regulation of structural plasticity of
      neuronal circuits. Here we examined the spatial and temporal differences in
      Wisteria floribunda agglutinin-labeled PNN intensity in single cells in the mouse
      hippocampus, where the neuronal circuits engaged in cognition and emotion are
      embedded in the dorsal and ventral parts, respectively. In young mice, the
      intensity of PNN was very low, and there were no significant dorsoventral
      differences in all hippocampal regions. Developmental increase in PNN intensity
      was larger in the dorsal part than in the ventral part. As a result, PNN
      intensity was higher in the dorsal part than in the ventral part in adult mice.
      Aging dissimilarly affects different regions of the dorsal hippocampus. Namely,
      PNN intensity in the dorsal part of old mice declined in the CA1 region, remained
      unchanged in the CA3 region, increased in the dentate gyrus. By contrast, there
      were no significant aging-related changes in PNN intensity in the ventral
      hippocampus. We also examined the intensity of parvalbumin (PV), an EF-hand
      calcium-binding protein, because it has been shown that PNNs are closely related
      to PV-containing GABAergic inhibitory neurons. Contrary to expectations,
      developmental and aging-related changes in PV intensity were not comparable to
      those seen in PNN intensity. The correlation coefficients between PNN and PV
      intensities in single cells showed gradual decline during development and aging
      in the CA1 and CA3 regions, while there were little correlations in the dentate
      gyrus regardless of age. In summary, PNNs are differentially expressed in the
      dorsal and ventral hippocampal circuits during development and aging, indicating
      their possible role for cognition and emotion control. 

PMID- 24016684
TI  - Almitrine fails to improve oxygenation during one-lung ventilation with
      sevoflurane anesthesia.
AB  - OBJECTIVE: Almitrine enhances hypoxic pulmonary vasoconstriction (HPV) and can
      improve hypoxemia related to one-lung ventilation (OLV). Studies using almitrine
      have been conducted without inhaled anesthetics because they could inhibit HPV,
      counteracting the effect of almitrine. This hypothesis, however, has not been
      confirmed. This study's aim was to evaluate whether almitrine could improve
      oxygenation when administered during OLV with sevoflurane anesthesia. DESIGN: A
      prospective, randomized, double-blind, placebo-controlled trial. SETTING: A
      tertiary care, university teaching hospital. PARTICIPANTS: Thirty adult patients
      undergoing open-chest thoracic surgery. INTERVENTIONS: Patients were assigned
      randomly to receive almitrine or placebo during OLV. Respiratory and hemodynamic
      variables were recorded continuously. Anesthesia was maintained with sevoflurane
      and remifentanil. Intraoperative techniques and medical teams were the same all
      over the study. MEASUREMENTS AND MAIN RESULTS: Respiratory and hemodynamic
      variables were measured during two-lung ventilation and during open-chest OLV.
      Two-way repeated-measures analysis of variance was used to compare the effects of
      almitrine and placebo. During OLV, PaO2 and shunt fraction worsened in all
      patients without significant differences between groups. At 30-minutes of OLV,
      PaO2 was 184+/-67 mmHg in the almitrine group and 145+/-56 mmHg in the placebo
      group, while shunt fraction were 31%+/-6% and 36%+/-13%, respectively. Mean
      pulmonary artery pressure was higher in the almitrine group (31+/-5 v 24+/-5
      mmHg, p<0.001). CONCLUSIONS: During anesthesia with sevoflurane for open-chest
      OLV, almitrine failed to improve oxygenation and increased pulmonary artery
      pressure. The combination of sevoflurane and almitrine should, therefore, be
      avoided.

PMID- 24016685
TI  - Future of awake cardiac surgery.

PMID- 24016686
TI  - Arterial closure devices for treatment of inadvertent large-caliber catheter
      insertion into the subclavian or carotid artery: a case series of five patients.

PMID- 24016687
TI  - Safe approach for chest reentry in a patient with large pseudoaneurysm of
      ascending aorta facilitated by intraoperative transesophageal echocardiography.

PMID- 24016688
TI  - Seasonal assessment of experimental vertical-flow constructed wetlands treating
      domestic wastewater.
AB  - The aim of this work was to compare the impact of different design (aggregate
      size) and operational (contact time, empty time and chemical oxygen demand (COD)
      loading) variables on the long-term and seasonal performance of vertical-flow
      constructed wetland filters operated in tidal flow mode. Compliance was achieved
      regarding ammonia-nitrogen, nitrate-nitrogen and suspended solids (SS), and non
      compliance concerning biochemical oxygen demand (BOD) and ortho-phosphate
      phosphorus. The filter with the highest COD loading performed the best regarding
      outflow COD concentration. Higher COD inflow concentrations had a significantly
      positive impact on the treatment performance for COD, ortho-phosphate-phosphorus
      and SS. The wetland with the largest aggregate size had the lowest mean nitrate
      nitrogen outflow concentration. However, the results were similar regardless of
      aggregate size and resting time for most variables. Clear seasonal outflow
      concentration trends (low in summer) were recorded for COD, ammonia-nitrogen and
      nitrate-nitrogen. No filter clogging was observed. 

PMID- 24016689
TI  - Treatment and course of different subtypes of status epilepticus.
AB  - Since randomized controlled trials are difficult to perform for ethical reasons
      in a potentially deadly condition like status epilepticus (SE), a retrospective
      database analysis may be welcome to broaden the evidence for the treatment of SE.
      In this retrospective study we evaluated every SE treatment at the neurological
      department of the University of Rostock from January 2000 to December 2009 in
      order to determine the efficacy of different antiepileptic drugs (AEDs) in
      terminating different kinds of SE. We analyzed the frequency of refractory
      courses in different types of SE, at which time which AED was administered and at
      which time which AED was effective to terminate the different epileptic
      conditions. A second aim of this study was to evaluate the course and the outcome
      of different kinds of SE. Statistical comparisons were performed with the chi(2)
      test. 167 episodes of SE in 118 patients could be evaluated. The efficacy rates
      of AEDs differed significantly, mainly due to the superior efficacy of clonazepam
      (CZP). CZP seemed to be more effective than DZP, LEV, MDM and VPA in terminating
      generalized convulsive status epilepticus (GCSE), whereas there was no
      significant difference in the efficacy for terminating nonconvulsive status
      epilepticus (NCSE) and epilepsia partialis continua (EPC) between the used AEDs.
      Anaesthesia and CZP both terminated GCSE more effectively than NCSE and EPC.
      Concerning the course of the different kinds of SE the following results were
      obtained: 13 patients died during hospital treatment. Treatment in NCSE and EPC
      started significantly later than in GCSE. There was no significant difference in
      mortality between the types of SE. However the frequency of refractory courses
      differed between the types of SE. At the time of SE termination without the
      administration of anaesthesia a combination therapy using 2 or more AEDs was
      established in most episodes. 

PMID- 24016690
TI  - Ultra-freeze induced cold contact wheals during cryosurgery: an uncommon subset
      of acquired cold contact urticaria.
AB  - Cryosurgery is a safe and effective therapeutic tool for a wide variety of
      cutaneous and mucocutaneous disorders. Side-effects include transient erythema
      and oedema. OBJECTIVE: A series of three patients presenting localized contact
      wheals minutes after contact with liquid nitrogen in the absence of clinical
      manifestations of cold urticaria is presented. METHODS: Specific cold diagnostic
      provocation tests with liquid nitrogen challenge test, ice cube test and Tempt
      test(r) were performed. RESULTS: The three patients showed an immediate wheal
      after cold contact with liquid nitrogen. The ice cube test, the temperature
      thresholds and the critical stimulation thresholds at 4?C assessed with the Tempt
      test 3.1(r) were negative. The induced wheals showed pathological features of
      urticaria. Eight patients suffering from acquired cold urticarial developed also
      liquid nitrogen induced wheals but none of the healthy controls. CONCLUSION: A
      peculiar subset of cold urticaria secondary to exposure to ultra-freeze
      temperatures developing in patients treated with cryotherapy is reported. The
      concept of "ultra-freeze urticaria" is proposed.

PMID- 24016691
TI  - Sensory experience differentially underlies developmental alterations of LTP in
      CA1 area and dentate gyrus.
AB  - Postnatal development of the brain relies on genetic codes and sensory inputs.
      The hippocampus, a well-known area of the brain involved in learning and memory,
      receives indirect sensory signals through the entorhinal cortex. Stimulating
      perforant path (PP) excitatory postsynaptic potentials (EPSPs) were recorded in
      dentate gyrus (DG) and CA1 area of hippocampus of the light (LR) and dark (DR)
      reared rats at 2 (2W), 6 (6W) and 10 weeks (10W) of postnatal age. Then, the PP
      was tetanized to induce LTP in both sites of recording. We found a developmental
      decrease in the amplitude of baseline EPSPs in either DG or CA1 area in the LR
      rats; opposite was the case in their DR counterparts. Potentiation level in both
      the CA1 and DG was lower in the DR compared to LR animals. Also, the magnitude of
      LTP was site-dependent where the degree of LTP was considerably higher in the CA1
      compared to the DG in either LR or DR rats. We concluded that: (a) visual signals
      are necessary for setting the basic activity of hippocampus to mature status, (b)
      visual deprivation negatively influences NMDA receptor-dependent hippocampal
      plasticity, (c) the CA1 and DG similarly respond to the sensory deprivation and
      (d) generally, LTP is weaker in the DG; irrelevant to degree of visual inputs to
      brain. 

PMID- 24016693
TI  - Prices on new insurance exchanges are lower than expected, report says.

PMID- 24016692
TI  - Voluntary exercise regionally augments rates of cerebral protein synthesis.
AB  - Exercise is a natural form of neurophysiologic stimulation that has known
      benefits for mental health, maintenance of cerebral function, and stress
      reduction. Exercise is known to induce an upregulation of brain-derived
      neurotrophic factor and this is thought to be involved in associated increases in
      neural plasticity. Protein synthesis is also an essential component of adaptive
      plasticity. We hypothesized that exercise may stimulate changes in brain protein
      synthesis as part of its effects on plasticity. Here, we applied the quantitative
      autoradiographic L-[1-(14)C]leucine method to the in vivo determination of
      regional rates of cerebral protein synthesis (rCPS) in adult rats following a
      seven day period of voluntary wheel-running and their sedentary counterparts. In
      four of 21 brain regions examined, the mean values of rCPS in the exercised rats
      were statistically significantly higher than in sedentary controls; regions
      affected were paraventricular hypothalamic nucleus, ventral hippocampus as a
      whole, CA1 pyramidal cell layer in ventral hippocampus, and frontal cortex.
      Increases in rCPS approached statistical significance in dentate gyrus of the
      ventral hippocampus. Our results affirm the value of exercise in encouraging
      hippocampal and possibly cortical neuroplasticity, and also suggest that exercise
      may modulate stimulation of stress-response pathways. Ultimately, our study
      indicates that measurement of rCPS with PET might be used as a marker of brain
      response to exercise in human subjects. 

PMID- 24016694
TI  - Exercise-induced vasovagal syncope.

PMID- 24016695
TI  - Localized rotational activation in the left atrium during human atrial
      fibrillation: relationship to complex fractionated atrial electrograms and low
      voltage zones.
AB  - BACKGROUND: In humans, the existence of rotors or reentrant sources maintaining
      atrial fibrillation (AF) and the underlying electroanatomic substrate has not
      been well defined. OBJECTIVE: Our aim was to determine the prevalence of
      localized rotational activation (RotA) in the left atrium (LA) during human AF
      and whether complex fractionated atrial electrograms (CFAEs) or low-voltage areas
      colocalize with RotA sites. METHODS: We prospectively studied 32 patients (mean
      age 57 +/- 8 years; 88% with persistent AF) undergoing AF catheter ablation.
      Bipolar electrograms were recorded for 2.5 seconds during AF using a roving 20
      pole circular catheter in the LA. RotA was defined as sequential temporal
      activation of bipoles around the circular catheter. Bipolar electrogram
      fractionation index and bipolar voltage were used to define CFAEs and low-voltage
      areas, respectively. RESULTS: In 21 (66%) patients, 47 RotA sites were
      identified. Few (9%) lasted 2.5 seconds (cycle length 183 +/- 6 ms), while the
      majority (91%) were nonsustained (duration 610 +/- 288 ms; cycle length 149 +/-
      11 ms). RotA was most common in the pulmonary vein antrum (71%) and posterior LA
      (25%). CFAEs were recorded from 18% +/- 12% of LA area, and most (92% +/- 7%)
      were not associated with RotA sites. However, 85% of RotA sites contained CFAEs.
      Very low voltage (<0.1 mV) areas comprised 12% +/- 10% of LA area and were
      present in 23% of RotA sites. CONCLUSIONS: In patients with predominantly
      persistent AF, localized RotA is commonly present but tends to be transient (<1
      second). Although most CFAEs do not colocalize with RotA sites, the high
      prevalence of CFAEs and very low voltages within RotA sites may indicate slow
      conduction in diseased myocardium necessary for their maintenance.

PMID- 24016696
TI  - Trainee inexperience is associated with longer procedure times but no increase in
      complications for cardiac device implantation.
AB  - BACKGROUND: The "July phenomenon" describes poor patient outcomes in teaching
      hospitals at the beginning of a new academic year when trainees begin. Whether
      this phenomenon truly exists is unclear. OBJECTIVE: The purpose of this study was
      to identify whether trainee and attending inexperience is associated with cardiac
      electrophysiologic procedural outcomes including total procedure time,
      fluoroscopy time, and complications. METHODS: We retrospectively reviewed the
      available electronic records of 488 consecutive patients undergoing initial dual
      chamber pacemaker (PM) or cardiac resynchronization therapy (CRT) device
      implantation performed at University of California, San Francisco from February
      2004 through November 2011. We calculated physician's year of experience using
      the procedure date and the physician's job start date. Patients were stratified
      into two subgroups based on their device type. Procedural outcomes including
      procedure length, fluoroscopy time, and complications were retrieved from
      electronic databases. RESULTS: After multivariate analysis, fellow experience was
      associated with decreased procedure time (19% less procedure time/year of
      experience, 95% confidence interval [CI] 13%-25%, P <.001 in the PM subgroup; and
      15% less procedure time/year of experience, 95% CI 7%-23%, P <.001 in the CRT
      subgroup). Fellow experience was associated with decreased fluoroscopy time in
      the CRT subgroup (19% less fluoroscopy time/experience years, 95% CI 5%-34%, P =
      .009). Neither fellow nor attending experience was associated with complications.
      CONCLUSION: Each year of fellow experience is associated with a decrease in
      cardiac device implantation procedure time and a decrease in fluoroscopy time
      during CRT implantation. No associations between fellow experience and in
      hospital complications were observed.

PMID- 24016697
TI  - Explorations into arrhythmia substrate in a common disease state: discovering a
      Bassaricyon neblina in the world of electrophysiology.

PMID- 24016698
TI  - Unusual response to entrainment of ventricular tachycardia: in or out?

PMID- 24016699
TI  - Identification and functional analysis of the peptidoglycan recognition protein
      LD gene in the mosquito, Armigeres subalbatus.
AB  - Peptidoglycan recognition proteins are important recognition proteins in many
      organisms ranging from echinoderms to humans. In an attempt to characterize all
      the PGRPs in the mosquito Armigeres subalbatus, two PGRP-LD isoforms, AsPGRP-LDa
      and AsPGRP-LDb, which are orthologs of the PGRP-LDs in several other insect
      species, were identified from this mosquito using homologous cloning. To date the
      functions of this PGRP gene have not yet been described in detail in other
      organisms with a known PGRP-LD gene. In the current study, we analyzed the
      sequences of these AsPGRP-LDs, their evolutionary relationships with their
      orthologs, their transcriptional expression in various developmental stages and
      different tissue samples, and their transcriptional responses to different
      bacterial stimuli. We then knocked down the expression of both AsPGRP-LDs by
      injection of double-stranded RNAs, and assessed the impact of AsPGRP-LD RNAi on
      mosquito survival after bacterial challenges and on the transcriptional
      expression of a number of antimicrobial peptides.

PMID- 24016700
TI  - Cardiovascular health among Philadelphia adolescents: analysis of youth risk
      behaviour data, 2011.
AB  - Improving population-level cardiovascular health is a public health priority.
      Guided by the American Heart Association's metrics for ideal heart health, we
      examined the prevalence of behavioural heart health indicators using a
      representative sample of urban adolescents. Less than 1% (0.6%) of the sample had
      ideal heart health. The alarmingly low percentage of ideal behavioural heart
      health suggests that primary prevention approaches to address cardiovascular
      health in youth are warranted. 

PMID- 24016701
TI  - Investigation of the factors associated with circulating soluble CD36 levels in
      patients with HCV-related chronic liver disease.
AB  - BACKGROUND: CD36, a class B scavenger receptor, participates in the pathogenesis
      of metabolic dysregulation such as insulin resistance, hepatic steatosis, and
      atherosclerosis. Persistent hepatitis C virus (HCV) infection often evokes these
      metabolic abnormalities. The primary purpose of this study was to investigate the
      role of CD36 in the pathogenesis of insulin resistance and hepatic steatosis
      caused by chronic HCV infection. METHODS: Forty-five patients with HCV-related
      chronic liver disease (CLD-C) were enrolled in this study. CD36 expression in the
      liver specimen was examined by an immunohistochemical procedure. The
      concentrations of circulating soluble form of CD36 (sCD36) and oxLDL were
      determined by the enzyme-linked innunosorbent assay. Insulin resistance was
      estimated by the values of HOMA-IR. RESULTS: Moderate to extensive hepatic CD36
      expression was observed in the sinusoids of all enrolled CLD-C patients. CD36
      positive sinusoids appeared to be identical to Kupffer cells. The severity of
      CD36 expression in the hepatic sinusoids was significantly correlated with the
      sCD36 level in sera of patients with CLD-C. The serum sCD36 levels were
      significantly correlated with body mass index and serum oxLDL levels in those
      patients. However, the serum sCD36 concentrations were independent of the values
      of HOMA-IR and the severity of hepatic steatosis. CONCLUSIONS: These data suggest
      that the serum sCD36 levels reflect the severity of CD36 expression on the
      Kupffer cells in patients with CLD-C, and that the serum sCD36 levels were
      associated with obesity, although the levels were independent of insulin
      resistance and hepatic steatosis in those patients.

PMID- 24016702
TI  - Focused beam reflectance measurement to monitor nimodipine precipitation process.
AB  - Crystallization of nimodipine in liquid-filled soft gelatin capsule during
      storage was reported for some commercial products, resulting in product recalls
      due to product quality and more importantly safety concerns. In this study, a
      real time particle monitoring tool, focused beam reflectance measurement, was
      used to evaluate the precipitation conditions of nimodipine in co-solvents. Upon
      water addition, two particle populations were discovered, appearing at different
      percentage of water content. Two transitions (i.e. sudden increase in particle
      counts) were observed, possibility related to nucleation and crystal growth of
      nimodipine. Furthermore, lowering storage temperature increased the tendency of
      nimodipine precipitation. Most critically, it was determined that with certain
      excipient, the drug precipitation occurred at approximately 7% (w/w) water
      content. Considering that all the orally administered liquid filled soft gelatin
      capsule shells contain residue water content as plasticizer, moisture transfer
      from the shell to the formulation may occur during long term storage, resulting
      in drug precipitation, particularly under cold temperature conditions. 

PMID- 24016703
TI  - Laparoscopic accuracy in prediction of appendiceal pathology: oncologic and
      inflammatory aspects.
AB  - BACKGROUND: In the prelaparoscopy era, macroscopically normal appendices were
      routinely resected. The aim of this study was to evaluate the accuracy of
      laparoscopy. METHODS: A review of 1,899 patients who underwent appendectomy with
      multivariate analysis was conducted. RESULTS: Laparoscopic and open approaches
      had similar false-positive rates, false-negative rates, accuracy, and
      sensitivity. The study population included 17 false-negative cases (11% of all
      macroscopically normal appendices). Tumors were found in 1.1% of our study
      population. Female gender (1.9% vs. .5%; odds ratio, 4; 95% confidence interval,
      1.5 to 11; P < .005) and appendiceal perforation were independent risk factors
      for harboring a tumor. CONCLUSIONS: It is suggested that laparoscopy has
      diagnostic quality similar to that of the open approach. Until randomized trials
      evaluate the fate of patients who receive false-negative diagnoses, routine
      appendectomy is recommended. Special attention should be paid to female patients
      and to patients with perforations, who have a 4-fold increased risk for harboring
      a tumor.

PMID- 24016704
TI  - American Association for the Surgery of Trauma Prevention Committee topical
      overview: National Trauma Data Bank, geographic information systems, and teaching
      injury prevention.
AB  - BACKGROUND: Injury is the leading cause of death for all Americans aged 1 to 35
      years, and injury-related costs exceed $100 billion per year in the United
      States. Trauma centers can be important resources for risk identification and
      prevention strategies. The authors review 3 important resources for injury
      prevention education and research: the National Trauma Data Bank, geographic
      information systems, and an overview of injury prevention education. DATA
      SOURCES: The National Trauma Data Bank and the Trauma Quality Improvement Program
      are available through the Web site of the American College of Surgeons. Links to
      research examples using geographic information systems software and the National
      Trauma Data Bank are provided in the text. Finally, resources for surgical
      educators in the area of injury prevention are summarized and examples provided.
      CONCLUSIONS: Database research, geographic information systems, and injury
      prevention education are important tools in the field of injury prevention. This
      article provides an overview of current research and education strategies and
      resources.

PMID- 24016705
TI  - Therapy choices and quality of life in young breast cancer survivors: a short
      term follow-up.
AB  - BACKGROUND: Premenopausal women represent approximately 35% of new breast cancer
      diagnoses. Diagnosis and treatment may lead to substantial disruption in quality
      of life (QOL). METHODS: Premenopausal patients (aged 18 to 50 years) treated for
      nonmetastatic breast cancer completed a mailed questionnaire. Multiple self
      reported QOL measures and clinical data were collected. Cluster analysis and
      Cronbach's alpha were used to validate the survey. Analysis of variance was
      performed for specific interventions. Lower interference scores conveyed higher
      QOL. RESULTS: The response rate was 49.8%. Cronbach's alpha was 0.96. Immediate
      contralateral prophylactic mastectomy (CPM) carried the highest interference
      (mean, 3.3148) with sexuality compared with no CPM (mean, 2.85) or delayed CPM (P
      = .03). Breast conservation had the least interference with appearance (P < .01)
      and work and finances (P = .02). CONCLUSIONS: Therapeutic mastectomy and CPM with
      or without reconstruction may adversely affect QOL. These findings suggest that
      the choice and timing of interventions may significantly affect patient
      satisfaction.

PMID- 24016706
TI  - Review of risk factors for the development of contralateral breast cancer.
AB  - BACKGROUND: Women treated for breast cancer have an increased risk for developing
      metachronous contralateral breast cancer (CBC). Patient perception of this risk
      is often overestimated and has been found to contribute to the decision to
      undergo contralateral prophylactic mastectomy. An individual's risk is dependent
      on both patient and tumor characteristics. This review examines and summarizes
      the current literature on the factors that affect CBC risk. DATA SOURCES: English
      language publications with the keyword "contralateral breast cancer" were
      identified through a MEDLINE literature search. CONCLUSIONS: The global incidence
      of CBC is decreasing, a trend that is attributed to more effective adjuvant
      therapies. Patients with BRCA germ-line mutations demonstrate the highest risk
      for CBC. In the absence of known genetic mutations, patients with strong family
      histories who are diagnosed at young ages (<35 years) with estrogen receptor
      negative index tumors appear to have a higher incidence of CBC.

PMID- 24016707
TI  - [Temporary vena caval filters: report on cohort of 72 patients in Grenoble,
      France].
AB  - Patients with a contra-indication for anticoagulation can benefit from temporary
      vena caval filters for protection against pulmonary embolism or recurrence. The
      filter can be removed secondarily, once the contra-indication is overcome,
      enabling better long-term outcome by reducing the risk of thrombotic and mechanic
      complications inherent in these devices. However, it has been shown in several
      studies that effective withdrawal rates were low and could be improved by the
      establishment of protocols and registries. We report a retrospective study of
      withdrawal in 72 patients in whom an ALN(r) vena caval filter was implanted at
      the Grenoble University Hospital over a period of three years with an intention
      for secondary retrieval. Seventy percent of the indications were related to the
      coexistence of thrombotic and hemorrhagic conditions. Fifty-five percent of
      filters were removed, the remaining 45% shared involved patients who died before
      retrieval (11%), those lost to follow-up (4%), technical failure of retrieval
      (6%), withdrawal technically unfeasible (3%), retrieval refused by patients (6%)
      and medical indications for continuing filtration (15%). Despite an effective
      follow-up of these patients and 91% success rate of withdrawal, nearly one out of
      two filters remains in place. A long-term follow-up of these patients is needed
      to learn more about the outcome of these filters.

PMID- 24016708
TI  - [Spontaneous rupture of a superior mesenteric artery: report of two cases].
AB  - Superior mesenteric artery aneurysms are rare. Diagnosis and treatment are a real
      challenge. We report two cases of this type of vascular anomaly revealed by
      spontaneous rupture. The diagnosis was made by abdominal computed tomography
      angiography and treatment consisted in aneurysmorraphy in one case and bowel
      resection with the distal aneurysm in the second. 

PMID- 24016709
TI  - Individualisation in crisis planning for people with psychotic disorders.
AB  - Background. In England, people with a serious mental illness are offered a
      standardized care plan under the Care Programme Approach (CPA). A crisis plan is
      a mandatory part of this standard; however, the quality and in particular the
      level of individualisation of these crisis plans are unknown. In this context,
      the aim of this study was to assess the quality of crisis planning and the impact
      of exposure to a specialized crisis planning intervention. Method. The crisis
      plans of 424 participants were assessed, before and after exposure to the Joint
      Crisis Plan (JCP) intervention, for 'individualisation' (i.e., at least one item
      of specific and identifiable information about an individual). Associations of
      individualisation were investigated. Results. A total of 15% of crisis plans were
      individualised at baseline. There was little or no improvement following exposure
      to the JCP. Individualised crisis plans were not associated with a history of
      prior crises or incidences of harm to self and others. Conclusions. Routine
      crisis planning for individuals with serious mental illness is not influenced by
      clinical risk profiles. 'Top down' implementation of the policy is unlikely to
      generate the best practice and compliance if clinicians do not perceive the
      clinical value in the process. 

PMID- 24016710
TI  - How to detect the yips in golf.
AB  - The yips is a multi-aetiological phenomenon that is characterized by an
      involuntary movement that can affect a golfer's putting performance. Diagnostics
      are crucial for a better understanding of what causes the yips but are still
      lacking. The purpose of the present study was therefore to identify sensitive
      methods for detecting the yips and evaluating its aetiology. Forty participants,
      20 yips-affected golfers and 20 nonaffected golfers, completed a psychometric
      testing battery and performed a putting session in the laboratory. They answered
      questions about their golfing and yips experience and filled in standardized
      questionnaires measuring trait anxiety, perfectionism, stress-coping strategies,
      somatic complaints, and movement and decision reinvestment. In the laboratory,
      they had to putt in five different conditions that might elicit the yips: as
      usual with both arms, under pressure, with one (the dominant) arm, with a
      unihockey racket, and with latex gloves. Measures included putting performance,
      situational anxiety, kinematic parameters of the putter, electromyography of the
      arm muscles, and electrocardiography. The groups were separated only by putting
      performance and kinematic parameters when putting with the dominant arm. Future
      research should use kinematics to investigate the aetiology of the yips and
      possible interventions. 

PMID- 24016711
TI  - Application of the Copenhagen Soccer Test in high-level women players - locomotor
      activities, physiological response and sprint performance.
AB  - We evaluated the physiological response, sprint performance and technical ability
      in various phases of the Copenhagen Soccer Test for Women (CSTw) and investigated
      whether the locomotor activities of the CSTw were comparable to competitive match
      play (CM). Physiological measurements and physical/technical assessments were
      performed during CSTw for eleven Norwegian high-level women soccer players. The
      activity pattern during CSTw and CM was monitored using the ZXY tracking system.
      No differences were observed between CSTw and CM with regards to total distance
      covered (10093+/-94 and 9674+/-191m), high intensity running (1278+/-67 and
      1193+/-115m) or sprinting (422+/-55 and 372+/-46m) (p>.05). During CSTw, average
      HR was 85+/-2%HRmax with 35+/-2% playing time >90%HRmax. Blood lactate increased
      (p<.05) from 1.4+/-0.3mM at rest to an average of 4.7+/-0.5mM during CSTw, with
      no changes during the test. Blood glucose was 5.4+/-0.3mM at rest and remained
      unaltered during CSTw. Sprint performance (2*20m) decreased (p<.05) by 3% during
      CSTw (8.19+/-0.06-8.47+/-0.10s). In conclusion, the locomotor activities during
      CSTw were comparable to that of high-level competitive match-play. The
      physiological demands of the CSTw were high, with no changes in heart rate, blood
      lactate or technical performance during the test, but a lowered sprint
      performance towards the end of the test. 

PMID- 24016712
TI  - Human variation and CYP enzyme contribution in benfuracarb metabolism in human in
      vitro hepatic models.
AB  - Human responses to the toxicological effects of chemicals are often complicated
      by a substantial interindividual variability in toxicokinetics, of which
      metabolism is often the most important factor. Therefore, we investigated human
      variation and the contributions of human-CYP isoforms to in vitro metabolism of
      benfuracarb. The primary metabolic pathways were the initial sulfur oxidation to
      benfuracarb-sulfoxide and the nitrogen-sulfur bond cleavage to carbofuran
      (activation). The Km, Vmax, and CL(int) values of carbofuran production in ten
      individual hepatic samples varied 7.3-, 3.4-, and 5.4-fold, respectively. CYP2C9
      and CYP2C19 catalyzed benfuracarb sulphur oxidation. Carbofuran formation,
      representing from 79% to 98% of the total metabolism, was catalyzed predominantly
      by CYP3A4. The calculated relative contribution of CYP3A4 to carbofuran formation
      was 93%, while it was 4.4% for CYP2C9. The major contribution of CYP3A4 in
      benfuracarb metabolism was further substantiated by showing a strong correlation
      with CYP3A4-selective markers midazolam-1'-hydroxylation and omeprazole
      sulfoxidation (r=0.885 and 0.772, respectively). Carbofuran formation was highly
      inhibited by the CYP3A inhibitor ketoconazole. Moreover, CYP3A4 marker activities
      were relatively inhibited by benfuracarb. These results confirm that human CYP3A4
      is the major enzyme involved in the in vitro activation of benfuracarb and that
      CYP3A4-catalyzed metabolism is the primary source of interindividual differences.

PMID- 24016713
TI  - Is the morbidity from the Longo hemorrhoidal technique acceptable?

PMID- 24016714
TI  - Evolution of low-grade systemic inflammation, insulin resistance,
      anthropometrics, resting energy expenditure and metabolic syndrome after
      bariatric surgery: a comparative study between gastric bypass and sleeve
      gastrectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) for morbid obesity is gaining
      in popularity as it offers several advantages over laparoscopic Roux-en-Y gastric
      bypass (LRYGBP), but comparative data between these two procedures have rarely
      been reported. METHODS: This case control study compared the incidence of low
      grade systemic inflammation, insulin resistance, anthropometrics, resting energy
      expenditure and metabolic syndrome in 30 patients undergoing LRYGBP and 30
      patients undergoing LSG, matched for age, sex, body mass index (BMI), and
      glycosylated hemoglobin (HbA1c). RESULTS: At 1-year after surgery, the percent of
      excess weight loss was 67.8 +/- 20.9 for LRYGBP and 61.6 +/- 19.4 for LSG.
      Patients undergoing LRYGBP showed significantly lower plasma levels of C-reactive
      protein (3.3 +/- 2.7 mg/dL vs. 5.3 +/- 3.9 mg/dL; P < 0.05), waist circumference
      (97.4 +/- 16.0 vs. 105.5 +/- 14.7 cm; P < 0.05), total cholesterol (4.6 +/- 1.0
      vs. 5.7 +/- 0.9 mmol/L; P < 0.01) and LDL cholesterol (2.6 +/- 0.8 vs. 3.6 +/-
      0.8 mmol/L; P < 0.01). Insulin resistance (HOMA index 1.6 +/- 1.0 after LRYGBP
      vs. 2.3 +/- 2.4 after LSG), resting energy expenditure (1666.7 +/- 320.5 after
      LRYGBP vs. 1600.4 +/- 427.3 Kcal after LSG) and remission of metabolic syndrome
      (92.9% after LRYGBP vs. 80% after LSG) were not different between the two groups.
      CONCLUSION: In this study, patients undergoing LRYGBP demonstrated significantly
      improved lipid profiles, decreased systemic low-grade inflammation compared with
      those undergoing LSG at 1-year follow-up.

PMID- 24016715
TI  - Local resection for small rectal cancer.
AB  - Rectal resection with total mesorectal excision is the standard treatment for
      rectal cancers. Local excision represents an alternative with less post-operative
      mortality and morbidity and preservation of intestinal and bladder function.
      However, local excision cannot provide adequate nodal staging. Presently,
      endorectal ultrasound and magnetic resonance imaging are used to select the
      appropriate patients for local excision, those with limited T1 rectal tumors.
      There is general agreement that the ideal tumors for local excision are less or
      equal to 3 cm in diameter, superficial (usTis and/or usT1N0), infra-peritoneal,
      located below the middle rectal valve, and involving no more than 40% of the
      rectal circumference. Transanal tumor excision is suitable for distal tumors and
      transanal endoscopic microsurgery for mid and upper lesions. The principles of
      adequate resection margin, non-fragmentation, and full-thickness excision are
      similar to those for any cancer resection. Unfavorable pathologic criteria, as
      assessed on the fixed rectal specimen, include depth of tumor invasion
      (submucosal [T1sm3] or muscular [T2]), positive resection margins, vascular
      and/or lymphatic invasion, and poor differentiation. Further radical surgery is
      required in case of unfavorable criteria. Simple surveillance may be advised for
      superficial tumors (T1sm1) without any unfavorable criteria. Management of T1sm2
      tumors without any unfavorable criteria should be discussed on a case-by-case
      basis.

PMID- 24016716
TI  - Pressurized nano-liquid-junction interface for coupling capillary
      electrochromatography and nano-liquid chromatography with mass spectrometry.
AB  - A new nano-liquid-junction interface for coupling both capillary
      electrochromatography (CEC) or nano-liquid chromatography (nano-LC) with mass
      spectrometry (MS) was studied. The interface was a small T piece of polymeric
      material where capillary column and tip capillary were positioned at 180 degrees 
      while the third exit (at 90 degrees ) was occupied by a capillary delivering a
      liquid-assisting spray ionization for CEC experiments or by the electrode for the
      high voltage spray for nano-LC. Experiments were carried out analyzing mixtures
      of some organophosphorus pesticides (OPPs) or anti-inflammatory and related
      acidic drugs with MS detection in positive or negative ion mode, respectively.
      Analyzed OPPs compounds were baseline resolved utilizing the novel interface in
      both nano-LC and CEC obtaining good sensitivity and repeatability. For CEC-MS,
      the limits of detection ranged between 0.03 and 6.80 MUg/mL and the intra-day
      repeatability was RSD <3.8% and <13% for the retention times and peak areas,
      respectively. The interface was easy to handle and good reproducibility, between
      2.5 and 3.5% for the retention time and <10% for the efficiencies, was obtained
      when the interface was installed by two different analysts. Furthermore, it could
      be used for both CEC and nano-LC.

PMID- 24016717
TI  - Analytical characterization of complex, biotechnological feedstocks by pH
      gradient ion exchange chromatography for purification process development.
AB  - The accelerating growth of the market for proteins and the growing interest in
      new, more complex molecules are bringing new challenges to the downstream process
      development of these proteins. This results in a demand for faster, more cost
      efficient, and highly understood downstream processes. Screening procedures based
      on high-throughput methods are widely applied nowadays to develop purification
      processes for proteins. However, screening highly complex biotechnological
      feedstocks, such as complete cell lysates containing target proteins often
      expressed with a low titre, is still very challenging. In this work we
      demonstrate a multidimensional, analytical screening approach based on pH
      gradient ion exchange chromatography (IEC), gel electrophoresis and protein
      identification via mass spectrometry to rationally characterize a
      biotechnological feedstock for the purpose of purification process development.
      With this very simple characterization strategy a two-step purification based on
      consecutive IEC operations was rapidly laid out for the purification of a
      diagnostic protein from a cell lysate reaching a purity of ~80%. The target
      protein was recombinantly produced using an insect cell expression system. 

PMID- 24016718
TI  - Comprehensive profiling of 136 tetra- to octa-polychlorinated dibenzo-p-dioxins
      and dibenzofurans using ionic liquid columns and column combinations.
AB  - The orders of elution of all 136 tetra- to octa-chlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) were determined on six gas chromatography (GC) columns.
      Three of these columns had ionic liquid stationary phases (SLB-IL111, SLB-IL76
      and SLB-IL61; Supelco), one a liquid crystal phase (LC-50; Restek), one a chiral
      phase (betaDEXcst; Restek) and one a low bleed non-polar phase (DB-XLB;
      J&W/Agilent). According to our results, the high polarity and multiple solvation
      interactions of the ionic liquid stationary phases offered superior resolving
      power to that achieved with previously evaluated columns. The SLB-IL61 and SLB
      IL111 columns resolved or partially separated 106 and 100 congeners,
      respectively, of the 136 PCDD/Fs. The SLB-IL61 also resolved 15 and partially
      separated one of the seventeen 2,3,7,8-substituted PCDD/Fs. Additional congeners
      can be separated by complementary analyses using additional columns in a dual- or
      triple-column approach. For example, using a combination of the SLB-IL61 and SLB
      IL111 columns all but 8 congeners would be separated, including all 2,3,7,8
      substituted PCDD/Fs. Two more congeners would be separated using a combination of
      SLB-IL76 and a liquid crystal (SB-Smectic) column, but in this case the 2,3,7,8
      TeCDF would not be resolved. Three-column combinations would give even better
      separation: the DB-17/Smectic/SLB-IL76 and DB-225/Smectic/SLB-IL111 combinations
      would separate all but 1 of the 136 PCDD/F congeners. Unfortunately, the smectic
      column is no longer in production. If only commercially available columns are
      considered, combinations of SLB-IL61 and SLB-IL111 with DB-XLB, LC-50, or DB-225
      offer the best performance, with 4, 4, and 3 unresolved congeners, respectively.
      Moreover, in each of these cases, one of the congeners in each unresolved pair is
      resolved on at least one of the other columns and so a reasonable estimate of the
      unresolved congeners' concentrations can be obtained by subtraction. The
      profiling of all 136 PCDD/Fs is thus greatly facilitated by using ionic liquid
      columns or combinations including such columns. However, there is room for
      improvement in the technical performance of the evaluated ionic liquid columns:
      their long-term retention time stability was poor and some highly chlorinated and
      sterically hindered congeners underwent dehalogenation during separation. 

PMID- 24016719
TI  - On-matrix derivatization extraction of chemical weapons convention relevant
      alcohols from soil.
AB  - Present study deals with the on-matrix derivatization-extraction of aminoalcohols
      and thiodiglycols, which are important precursors and/or degradation products of
      VX analogues and vesicants class of chemical warfare agents (CWAs). The method
      involved hexamethyldisilazane (HMDS) mediated in situ silylation of analytes on
      the soil. Subsequent extraction and gas chromatography-mass spectrometry analysis
      of derivatized analytes offered better recoveries in comparison to the procedure
      recommended by the Organization for the Prohibition of Chemical Weapons (OPCW).
      Various experimental conditions such as extraction solvent, reagent and catalyst
      amount, reaction time and temperature were optimized. Best recoveries of analytes
      ranging from 45% to 103% were obtained with DCM solvent containing 5%, v/v HMDS
      and 0.01%, w/v iodine as catalyst. The limits of detection (LOD) and limit of
      quantification (LOQ) with selected analytes ranged from 8 to 277 and 21 to
      665ngmL(-1), respectively, in selected ion monitoring mode. 

PMID- 24016720
TI  - Pushing the performance limits of reversed-phase ultra high performance liquid
      chromatography with 1.3MUm core-shell particles.
AB  - Innovative columns made with very small core-shell particles (1.0-1.4MUm) were
      investigated over a wide experimental space using state-of-the-art ultra high
      performance liquid chromatography (UHPLC) instruments. Among the columns tested
      is one that is now commercially available and is made with 1.3MUm core-shell
      particles consisting of non-porous cores about 0.9MUm in size and porous shells
      <0.2MUm thick. This work demonstrated that exceptionally low observed minimum
      plate heights of 2.2MUm could be obtained using columns packed with 1.3MUm
      particles, corresponding to a plate count of over 450,000 plates/m. It was shown
      that only low volume columns allow operation under optimal conditions with
      current top-of-the-line UHPLC instruments. It was also demonstrated that the loss
      in performance caused by frictional heating effects remains negligible. Finally,
      the practical utility of these columns was confirmed with several real-world
      applications requiring extreme resolving power (i.e. peptide mapping, sample
      typical of metabolomic studies and crude human insulin). The performance achieved
      was compared to that of a reference UHPLC column packed with 1.7MUm fully porous
      particles. The column packed with 1.3MUm particles gave peak capacity values that
      were 20-40% higher than the reference column for the same analysis time. 

PMID- 24016721
TI  - Profiling the fatty acids from a strain of the microalgae Alexandrium tamarense
      by means of high-speed counter-current chromatography and gas chromatography
      coupled with mass spectrometry.
AB  - Fatty acids of microalgae have been studied as potential chemotaxonomic markers,
      to reveal plausible lipid phycotoxins or in the context of mass production of
      algal biofuels. The planctonic microalgae Alexandrium tamarense (Dinophyceae) is
      a common harmful algal bloom species that often proliferates in eutrophic costal
      waters. Alexandrium blooms are the proximal source of toxins associated with
      paralytic shellfish poisoning (PSP), a neurological affliction that has caused
      human illness for centuries via consumption of contaminated shellfish. However,
      data on the fatty acid composition of A. tamarense is currently limited. For this
      reason, we cultivated a well-defined strain of A. tamarense (Alex2, group I,
      North American clade) in order to study both its major and minor fatty acids. The
      harvested microalgae were transesterified and the fatty acid methyl esters were
      fractionated by means of high-speed counter-current chromatography (HSCCC). The
      resulting 31 HSCCC fractions were analyzed by gas chromatography with mass
      spectrometry (GC/MS). Unknown substances were identified by transferring assorted
      HSCCC fractions into picolinyl or pyrrolidide derivatives. Twenty fatty acids
      (range 0.2-22.9% contribution to total fatty acids) were identified in the
      unfractionated sample with 14:0, 16:0, 18:1n-9, 18:4n-3, 18:5n-3 and 22:6n-3
      representing>80% of the total fatty acids. HSCCC fractionation enabled the
      identification of further 22 trace fatty acids contributing between ~0.01 and
      0.2% to total fatty acids. The fatty acids included several branched-chain fatty
      acids as well as scarcely reported fatty acids like 11-methyl-18:1n-6tr or
      18:2Delta4,9. In order to enable a better comparability and repeatability of
      HSCCC fractionations, we calculated for each HSCCC fraction the total volume of
      mobile phase, which had passed the HSCCC. From this volume we subtracted the
      volume of extruded stationary phase and divided the corrected volume by the total
      coil volume. These elution values were in good agreement with the partition
      ratios of randomly chosen fatty acid methyl esters obtained in shake flask tests,
      which allows the prediction of the elution from the HSCCC system when the
      partition ratio is known. 

PMID- 24016722
TI  - In vitro and in vivo toxicities of sediment and surface water in an area near a
      major steel industry of Korea: endocrine disruption, reproduction, or survival
      effects combined with instrumental analysis.
AB  - The influence of industrial and/or municipal contaminant inputs on the aquatic
      environment of Pohang, Korea was investigated, with a focus on bioassay combined
      with instrumental analysis. Pohang is the most heavily populated city in
      Gyeongsangbuk-do province of Korea, with more than half a million residents, and
      also hosts the nation's biggest steel manufacturer and related industries.
      Sediment (n=15) and surface water samples (n=17) were collected from Hyeongsan
      River which runs across the Pohang city, in two separate events, i.e., June 2010
      and February 2011. Sediment samples were first Soxhlet-extracted (raw extract)
      and were measured for estrogenicity using H295R cell line, and also analyzed for
      alkylphenols (APs), bisphenol A (BPA), PAHs, and PCBs. For sediment samples which
      exhibited greatest effects in the cell line, further fractionation was performed
      into non-polar, mid-polar, and polar portions. In surface water samples, heavy
      metals were also analyzed. Among 15 sediment samples, station S2 near the steel
      industry complex and station M3 near the municipal area showed the greatest sex
      hormone changes, and these changes were generally explained by the fractions
      which contained APs and BPA. Principal component analysis (PCA) however suggests
      that chemicals that were not analyzed in the present study would better explain
      endocrine disruption capacity of sediments. In water samples, adverse effects on
      hatchability and growth of Japanese medaka fish, and on Daphnia reproduction were
      noted following exposure to six water samples collected from stations near
      industrial and municipal areas. Several heavy metals and nonylphenol (NP)
      concentrations exceeded surface water quality guidelines, suggesting adverse
      effects of contamination inputs from both industrial and municipal activities.
      Observed estrogenicities in stations such as S2 and M3 warrant further
      investigations on longer term ecosystem impacts near industrial and municipal
      areas. The levels of major organic chemicals in sediments are quite comparable to
      those reported in ~10 years ago, emphasizing a need for source control.

PMID- 24016723
TI  - An alternative method of OBT measurement for the limited quantity of
      environmental samples using a combustion bomb.
AB  - The measurement of organically bound tritium (OBT) in environmental samples is
      much more difficult than the measurement of tritiated water (HTO). This study
      describes an alternative method for OBT determination in plant materials in which
      tritium-free polyethylene beads are added to the plant sample prior to combustion
      in a combustion bomb. It is not always possible to collect large enough amounts
      of some plants (e.g. algae, plankton, grass) within a specific area or specific
      period. Excellent water recovery is achieved when dry plant materials are
      combusted with polyethylene beads. When Ultima Gold AB is used as the
      scintillation cocktail, it is possible to measure the combustion water directly
      without distillation. Correction factors were derived for the plants used in the
      study to account for the dilution of the combustion water due to addition of the
      polyethylene beads. The alternative method has a number of advantages, including
      an increased yield of combustion water for liquid scintillation counting, less
      color quenching, reduced sample size and decreased analysis time. Finally,
      accuracy tests comparing results of the conventional method with those of the
      alternative method were carried out using environmental samples. 

PMID- 24016724
TI  - Impairments in both reward and punishment guided reinforcement learning in
      schizophrenia.

PMID- 24016725
TI  - Differential spatiotemporal characteristics of the prefrontal hemodynamic
      response and their association with functional impairment in schizophrenia and
      major depression.
AB  - Recent neuroimaging studies have shown similarities and differences in prefrontal
      abnormalities between patients with schizophrenia (SZ) and major depressive
      disorder (MDD). However, the differential spatiotemporal characteristics of these
      abnormalities and their association with functional impairment remain unclear. To
      elucidate differential brain pathophysiology in these disorders, we used
      multichannel near-infrared spectroscopy (NIRS) to measure the spatiotemporal
      characteristics of prefrontal activation and investigated their association with
      global functioning levels. The study included 96 individuals: 32 patients with
      SZ, 32 patients with MDD, and 32 demographically matched healthy subjects. During
      a verbal fluency task, the changes in oxygenated and deoxygenated hemoglobin
      ([oxy-Hb] and [deoxy-Hb]) signals over the prefrontal cortex (PFC) were measured
      using 52-channel NIRS and compared among the 3 groups. Patients with SZ and MDD
      showed lesser-than-normal [oxy-Hb] activation during the task, whereas the
      initial slope of [oxy-Hb] activation was steeper for patients with MDD than for
      patients with SZ. The reduced hemodynamic response was associated with lower
      global functioning, and the correlative regions were different between the 2
      disorders (frontopolar PFC in SZ; dorsolateral and ventrolateral PFC in MDD). The
      hypofrontality observed in patients with SZ and MDD is consistent with the
      findings of previous neuroimaging studies. Moreover, the spatiotemporal
      characteristics and the functional significance of the prefrontal hemodynamic
      response could differentiate the 2 psychiatric disorders. These results suggest a
      differential brain pathophysiology between SZ and MDD. Future large-scale studies
      are needed to determine the practical applicability of these findings for
      clinical diagnosis and evaluation. 

PMID- 24016726
TI  - Task-related fronto-striatal functional connectivity during working memory
      performance in schizophrenia.
AB  - Working memory (WM) deficits and associated brain dysfunction are among the most
      well replicated candidate endophenotypic processes in schizophrenia. However,
      previous studies demonstrate inconsistent over- and under-activation of
      dorsolateral and ventrolateral prefrontal cortices (DLPFC; VLPFC), inferior
      parietal lobule (IPL) during WM performance, as well as subcortical structures
      including the striatum, and dysfunctional connectivity among fronto-striatal
      regions in schizophrenia. However, no previous study has investigated task
      related functional connectivity (FC) of DLPFC and striatal regions using a seed
      based method; here we employed this method to assess patterns of cortical and
      subcortical functional connectivity among WM structures during a standard 2-back
      WM task performed by 28 schizophrenia (SZ) and 28 healthy controls (HC). Initial
      group comparisons of blood oxygenation level dependent (BOLD) responses during
      the WM task revealed significantly greater bilateral activity in the striatum in
      SZ relative to HC, but there was no significant group difference in WM cortical
      activity (right DLPFC, VLPFC or IPL). Analyses of FC within the cortico
      subcortical WM network in the HC group revealed positive performance-related FC
      between the right DLPFC and the right caudate, and between the right VLPFC and
      the right IPL; this pattern was absent in SZ. In contrast, SZ patients showed
      negative performance-related functional connectivity between the left putamen and
      the right VLPFC. Direct group comparisons in functional connectivity showed
      significantly greater performance-related FC between the VLPFC and bilateral
      putamen, as well as unilaterally between the VLPFC and the right IPL, in HC.
      Results suggest a critical dysfunction of cortico-striatal connectivity
      underpinning information retrieval for SZ patients during WM performance. 

PMID- 24016727
TI  - Evidence for dysregulated high-frequency oscillations during sensory processing
      in medication-naive, first episode schizophrenia.
AB  - INTRODUCTION: High-frequency oscillations are important for sensory processing
      and dysfunctions in the amplitude and synchrony of beta- and gamma-band
      oscillations have been demonstrated in schizophrenia (ScZ). However, the presence
      of aberrant high-frequency oscillations in first-episode (FE), medication-naive
      patients during sensory processing is unclear. METHODS: Magnetoencephalographic
      (MEG) data were recorded from 15 never-medicated, FE-ScZ patients and 20 matched
      healthy controls during the perception of Mooney faces. MEG data were analysed
      for spectral power and single-sensor phase-locking in the beta (13-25Hz) and
      gamma- (25-140Hz) frequency range. RESULTS: FE-ScZ patients were characterized by
      significantly impaired sensory processing as indicated by a reduced
      discrimination index (A'). Impaired behavioural performance in ScZ-patients was
      accompanied by decreased spectral power in the high- (60-120Hz) gamma-band range.
      In contrast, oscillations in the lower (25-60Hz) gamma-band were largely intact
      and beta-band oscillations were increased. Analysis of cross-frequency coupling
      showed a reduced correlation between 60 and 120Hz amplitude values and beta-band
      power in FE-ScZ-patients relative to controls. DISCUSSION: Our findings show that
      impaired sensory processing in medication-naive, FE-schizophrenia is related to a
      dysregulation of neural oscillations which involves both an impairment in the
      generation of high gamma-band activity as well as a failure to downregulate task
      irrelevant beta-band activity. Because of the interrelationship of these
      dysfunctions and the role of inhibitory networks in the shaping of high-frequency
      activity, aberrant neural oscillations in FE-schizophrenia may be linked to
      dysfunctions in the excitation-inhibition (E/I)-balance.

PMID- 24016728
TI  - Protecting the public or setting the bar too high? Understanding the causes and
      consequences of regulatory actions of front-line regulators and specialized drug
      shop operators in Kenya.
AB  - The problem of poor regulatory compliance has been widely reported across private
      health providers in developing countries. Less known are the underlying reasons
      for poor compliance, especially with regards to the roles played by front-line
      regulatory staff, and the regulatory institution as a whole. We designed a
      qualitative study to address this gap, with the study questions and tools drawing
      on a conceptual framework informed by theoretical literature on regulation. Data
      were collected from specialized drug shops (SDSs) in two rural districts in
      Western Kenya in 2011 through eight focus group discussions, and from regulatory
      staff from organizations governing the pharmaceutical sector through a total of
      24 in-depth interviews. We found that relationships between front-line regulators
      and SDS operators were a strong influence on regulatory behaviour, often
      resulting in non-compliance and perverse outcomes such as corruption. It emerged
      that separate regulatory streams operated in urban and rural locations, based
      mainly on differing relationships between the front-line regulators and SDS
      operators, and on broader factors such as the competition environment and
      community expectations. Effective incentive structures for regulatory staff were
      either absent, or poorly linked to performance in regulatory organizations,
      resulting in divergences between the purposes of the regulatory organization and
      activities of front-line staff. Given the rural-urban differences in the practice
      environment, the introduction of lower retail practice requirements for rural
      SDSs could be considered. This would allow illegally operated shops to be brought
      within the regulatory framework, facilitating good quality provision of essential
      commodities to marginalized areas, without lowering the practice requirements for
      the better complying urban SDSs. In addition, regulatory organizations need to
      devise incentives that better link the level of effort to rewards such as
      professional advancement of regulatory staff. 

PMID- 24016729
TI  - Phenindione interferes with measurement of creatinine.

PMID- 24016731
TI  - Staphylococcus aureus: the innocent culprit?

PMID- 24016730
TI  - Single nucleotide polymorphisms in candidate genes and dengue severity in
      children: a case-control, functional and meta-analysis study.
AB  - Dengue is an arthropod-borne emerging viral disease with high morbidity and
      mortality risk in tropical countries like Brazil. Clinical manifestations are
      vast, ranging from asymptomatic to most severe forms of dengue such as shock.
      Previous data have shown that host genetics play a role in disease susceptibility
      and severity. Herein, we have tested the association of single nucleotide
      polymorphisms (SNPs) at TNF, IL10, MIF, DCSIGN, CLEC5A, NOD2, CCR5 and MRC1 as
      candidate genes using a matched case-control study design including 88 severe
      children cases of dengue patients and 335 healthy unrelated subjects that was
      also separated in IgG(+) and IgG(-) controls. We demonstrated that the TT
      genotype of CLEC5A SNP (rs1285933 C>T) is associated with dengue severity
      (OR=2.25; p=0.03) and that GG genotype of -336G>A DCSIGN (CD209) SNP is
      associated with protection to severe dengue (OR=0.12; p=0.04). Both comparisons
      were borderline significant when cases were compared with IgG(+) controls
      subgroup. Nevertheless, genotype-phenotype correlation was also assessed using
      serum levels of TNF from infected patients at the onset of dengue fever, and
      CT/TT carriers in CLEC5A secreted higher levels of TNF than CC individuals in 5-7
      days of infection. No significant difference was observed in TNF levels between
      genotypes GG versus AG/AA at DCSIGN promoter. Next, we performed a meta-analysis
      retrieving results from the literature for -336G>A DCSIGN and -308G>A TNF SNPs
      demonstrating that the consensus estimates of these SNPs indicated no association
      with dengue severity (when compared to Dengue fever) in the overall analysis.
      But, a subgroup analysis in the -336G>A DCSIGN, the G allele was associated with
      severe dengue susceptibility in Asians (ORallele=2.77; p=0.0001; ORcarriers=2.99;
      p=0.0001) and protection in Brazilians (ORallele=0.66; p=0.013). In summary, our
      results suggest that genetic variations at CLEC5A increase the risk and regulate
      TNF secretion in dengue severity among Brazilians. Also, combined data of the
      literature suggest population-specific effect of the -336 DCSIGN SNP more
      prominent in Asians and in a different direction than Brazilians.

PMID- 24016732
TI  - Hybrid ZnO/phthalocyanine photovoltaic device with highly resistive ZnO
      intermediate layer.
AB  - We report a hybrid photovoltaic device composed of a 3.3 eV bandgap zinc oxide
      (ZnO) semiconductor and metal-free phthalocyanine layers and the effects of the
      insertion of the highly resistive ZnO buffer layer on the electrical
      characteristics of the rectification feature and photovoltaic performance. The
      hybrid photovoltaic devices have been constructed by electrodeposition of the 300
      nm thick ZnO layer in a simple zinc nitrate aqueous solution followed by vacuum
      evaporation of 50-400 nm thick-phthalocyanine layers. The ZnO layers with the
      resistivity of 1.8 * 10(3) and 1 * 10(8) Omega cm were prepared by adjusting the
      cathodic current density and were installed into the hybrid photovoltaic devices
      as the n-type and buffer layer, respectively. The phthalocyanine layers with the
      characteristic monoclinic lattice showed a characteristic optical absorption
      feature regardless of the thickness, but the preferred orientation changed
      depending on the thickness. The ZnO buffer-free hybrid 50 nm thick
      phthalocyanine/n-ZnO photovoltaic device showed a rectification feature but
      possessed a poor photovoltaic performance with a conversion efficiency of 7.5 *
      10(-7) %, open circuit voltage of 0.041 V, and short circuit current density of
      8.0 * 10(-5) mA cm(-2). The insertion of the ZnO buffer layer between the n-ZnO
      and phthalocyanine layers induced improvements in both the rectification feature
      and photovoltaic performance. The excellent rectification feature with a
      rectification ratio of 3188 and ideally factor of 1.29 was obtained for the
      hybrid 200 nm thick phthalocyanine/ZnO buffer/n-ZnO photovoltaic device, and the
      hybrid photovoltaic device possessed an improved photovoltaic performance with
      the conversion efficiency of 0.0016%, open circuit voltage of 0.31 V, and short
      circuit current density of 0.015 mA cm(-2). 

PMID- 24016733
TI  - Thrombotic events in critically ill children with myocarditis.
AB  - BACKGROUND: Children with myocarditis have multiple risk factors for thrombotic
      events, yet the role of antithrombotic therapy is unclear in this population. We
      hypothesised that thrombotic events in critically ill children with myocarditis
      are common and that children with myocarditis are at higher risk for thrombotic
      events than children with non-inflammatory dilated cardiomyopathy. METHODS: This
      is a retrospective chart review of all children presenting to a single centre
      cardiac intensive care unit with myocarditis from 1995 to 2008. A comparison
      group of children with dilated cardiomyopathy was also examined. Antithrombotic
      regimens were recorded. The primary outcome of thrombotic events included
      intracardiac clots and any thromboembolic events. RESULTS: Out of 45 cases with
      myocarditis, 40% were biopsy-proven, 24% viral polymerase chain reaction
      supported, and 36% diagnosed based on high clinical suspicion. There were two
      (4.4%) thrombotic events in the myocarditis group and three (6.7%) in the dilated
      cardiomyopathy group (p = 1.0). Neither the use of any antiplatelet or
      anticoagulation therapy, use of intravenous immune globulin, presence of any
      arrhythmia, nor need for mechanical circulatory support were predictive of
      thrombotic events in the myocarditis, dilated cardiomyopathy, or combined groups.
      CONCLUSIONS: Thrombotic events in critically ill children with myocarditis and
      dilated cardiomyopathy occurred in 6% of the combined cohort. There was no
      difference in thrombotic events between inflammatory and non-inflammatory
      cardiomyopathy groups, suggesting that the decision to use antithrombotic
      prophylaxis should be based on factors other than the underlying aetiology of a
      child's acute decompensated heart failure.

PMID- 24016734
TI  - A family history of serious complications due to BCG vaccination is a tool for
      the early diagnosis of severe primary immunodeficiency.
AB  - Severe Combined Immunodeficiency (SCID) is one of the most severe forms of
      primary immunodeficiency (PID). Complications of BCG vaccination, especially
      disseminated infection and its most severe forms, are known to occur in
      immunodeficient patients, particularly in SCID. A carefully taken family history
      before BCG injection as well as delaying vaccination if PID is suspected could be
      a simple and effective method to avoid inappropriate vaccination of an
      immunodeficient child in some cases until the prospect of newborn screening for
      SCID has been fully developed. We describe a patient with a very early diagnosis
      of SCID, which was suspected on the basis of the previous death of two siblings
      younger than one year due to severe complications secondary to the BCG vaccine.
      We suggest that a family history of severe or fatal reactions to BCG should be
      included as a warning sign for an early diagnosis of SCID. 

PMID- 24016735
TI  - RepA and RepB exert plasmid incompatibility repressing the transcription of the
      repABC operon.
AB  - Rhizobium etli CFN42 has a multipartite genome composed of one chromosome and six
      large plasmids with low copy numbers, all belonging to the repABC plasmid family.
      All elements essential for replication and segregation of these plasmids are
      encoded within the repABC operon. RepA and RepB direct plasmid segregation and
      are involved in the transcriptional regulation of the operon, and RepC is the
      initiator protein of the plasmid. Here we show that in addition to RepA
      (repressor) and RepB (corepressor), full transcriptional repression of the operon
      located in the symbiotic plasmid (pRetCFN42d) of this strain requires parS, the
      centromere-like sequence, and the operator sequence. However, the co-expression
      of RepA and RepB is sufficient to induce the displacement of the parental
      plasmid. RepA is a Walker-type ATPase that self associates in vivo and in vitro
      and binds specifically to the operator region in its RepA-ADP form. In contrast,
      RepA-ATP is capable of binding to non-specific DNA. RepA and RepB form high
      molecular weight DNA-protein complexes in the presence of ATP and ADP. RepA
      carrying ATP-pocket motif mutations induce full repression of the repABC operon
      without the participation of RepB and parS. These mutants specifically bind the
      operator sequence in their ATP or ADP bound forms. In addition, their expression
      in trans exerts plasmid incompatibility against the parental plasmid. RepA and
      RepB expressed in trans induce plasmid incompatibility because of their ability
      to repress the repABC operon and not only by their capacity to distort the
      plasmid segregation process. 

PMID- 24016737
TI  - Omega-3 intake in people with obstructive sleep apnea: beauty sleep for the
      heart.

PMID- 24016738
TI  - [Determinants of low birth weight among newborns to HIV-infected mothers not
      eligible for antiretroviral treatment in Africa].
AB  - BACKGROUND: Low birth weight (LBW) increases the risk of infant death, but little
      is known about its rate and determinants among babies born to HIV-infected
      mothers in sub-Saharan Africa. METHODS: This study was conducted in South Africa,
      Burkina Faso, Uganda and Zambia, during the recruitment process of the PROMISE
      PEP (ANRS 12174) clinical trial. The study sample included 1196 subjects screened
      between August 2009 and December 2011, respectively 254 in South Africa, 221 in
      Burkina Faso, 197 in Uganda and 524 in Zambia, all ineligible for antiretroviral
      therapy. Data were collected during ANRS12174 clinical trial antenatal and
      postnatal screening visits, and during an inclusion visit for completion of an
      electronic case report form (eCRF). RESULTS: The mean (+/-SD) age of mothers was
      27+/-5years and their mean CD4 count was 576+/-195cells/MUL. Most mothers lived
      in a couple (78.7%), had no employment (72.3%) and had a good level of education
      (74% had gone to school). Male newborns predominated (51.7%). The mean birth
      weight was 3043g+/-435g, and 7.8% ([95%CI: 6.3%-9.3%]) of newborns weighed less
      than 2500g. In univariate analyses, being married or cohabiting, body mass index,
      WHO HIV disease stage II, female newborn and low gestational age were associated
      with risk of LBW. In multivariate regression model, low gestational age
      (aOR=3.74, P<0.0001) and female newborn (aOR=1.63, P=0.04) were significantly
      associated with LBW. CONCLUSION: The risk factors for LBW found in HIV-infected
      women ineligible for antiretroviral therapy were the same as in the general
      population. There was no evidence of additional risk factors associated with HIV
      infection.

PMID- 24016739
TI  - Human papillomavirus vaccines in Picardy, France: coverage and correlation with
      socioeconomic factors.
AB  - BACKGROUND: In France, the human papillomavirus vaccine is routinely recommended
      for 14-year-old females and a "catch-up" vaccination should be offered to female
      adolescents who are between 15 and 23 years of age. Currently, few studies are
      available on the coverage rates in France. The aim of this study was to evaluate
      the coverage of the human papillomavirus vaccine and compliance with the
      vaccination scheme in Picardy, between 2009 and 2010, and to analyze the
      socioeconomic factors possibly influencing this coverage. METHODS: We selected a
      female population that was affiliated with the national health insurance
      organization, living in the Picardy region of France, and aged between 14 and 23
      years on 31st December 2010. RESULTS: The coverage rate in the study population
      with at least one dose of vaccine was 16.8%. A complete vaccination scheme (three
      doses) was observed in less than 38.9% of them, so only 6.5% of this population
      had received the complete vaccination. Higher rates of coverage and compliance
      were observed in girls 14 years of age (65.5%) and if the prescriber was a
      gynecologist or pediatrician (respectively, 44.7% and 48.1%). There is a negative
      correlation between coverage and compliance and the percentage of single-parent
      families and immigrant families by canton area of Picardy. The economic cost of
      an inappropriate scheme was 1.3 million euros for Picardy in 2009. CONCLUSION:
      Coverage and compliance rates of human papillomavirus vaccines in Picardy appear
      to be low. This study suggests that health authorities in Picardy should provide
      communication and action campaigns to improve these results.

PMID- 24016740
TI  - Changing name: changing prospects for psychosis.
AB  - Names matter! Schizophrenia has negative associations which impede individual
      recovery and induce societal and self-stigmatization. Alternatives have been
      proposed and are worthy of debate; changes made in Japan have generally been
      considered successful. The group of 'schizophrenia and other psychoses' could be
      further differentiated based on the major social factors identified, i.e. drug
      misuse and the effects of severe childhood trauma. The use of appropriate
      International Classification of Diseases (ICD) coding and definitions could
      usefully differentiate these groups - the former is a drug-induced psychosis and
      the latter frequently presents as comorbid schizophrenia and borderline
      personality disorder (often attracting a diagnosis of schizoaffective disorder).
      The current established differentiation between early onset ('stress-sensitive' -
      'Kraepelinian' schizophrenia) and later onset (DSM5 delusional disorder, i.e.
      with 'non-bizarreness' criterion removed) psychosis may also be worthy of further
      investigation to establish validity and reliability. Psychosocially descriptive
      terms have been found to be more acceptable to patients and perceived as less
      stigmatizing by others. Subgroups of psychosis with greater homogeneity would
      benefit research, clinical and therapeutic practice and public understanding,
      attitudes and behaviour. 

PMID- 24016741
TI  - Gastrointestinal gene delivery by cyclodextrins--in vitro quantification of
      extracellular barriers.
AB  - Local gene delivery represents a promising therapeutic approach for diseases of
      the intestine. However, the gastrointestinal tract poses significant challenges
      to successful gene delivery. Cyclodextrins (CDs) have been extensively
      investigated as non-viral vectors. Here, we assessed the suitability of an
      amphiphilic cationic CD for intestinal gene transfer, with particular focus on
      extracellular barriers. Stability and transfection efficiency of CD.DNA complexes
      were assessed post incubation in simulated gastric and intestinal fluids, bile
      salts and mucin, or with intestinal enzymes to represent extracellular barriers
      to intestinal gene delivery. Stability was determined by gel electrophoresis and
      transfection was measured by luciferase expression in intestinal epithelial cells
      (Caco-2). Transfection efficiency of CD.DNA complexes was enhanced after
      incubation in bile salts but was reduced after incubation in gastric and
      intestinal fluids and mucin. CD.DNA complexes were stable after incubation with
      pancreatic enzymes and with a model lower intestinal enzyme. Furthermore, the CD
      protected pDNA from degradation by DNase. In summary, physiologically relevant in
      vitro models were established and used to quantify the barriers posed by the
      intestinal extracellular environment to gene delivery. This systematic assessment
      identified the advantages and limitations of the CD vector and facilitated the
      proposal of formulation strategies to overcome these barriers. 

PMID- 24016742
TI  - Folate-modified poly(2-ethyl-2-oxazoline) as hydrophilic corona in polymeric
      micelles for enhanced intracellular doxorubicin delivery.
AB  - The transmembrane transport of drug loaded micelles to intracellular compartment
      is quite crucial for efficient drug delivery. In the current study, we
      investigated the cellular internalization and anticancer activity of doxorubicin
      loaded micelles with folate modified stealthy PEOz corona. Folate-decorated
      micelles incorporating doxorubicin were characterized for particle size, degree
      of folate decoration, drug loading content and encapsulation efficiency,
      morphology, and surface charge. The targeting capability and cell viability were
      assessed using HeLa, KB, A549 and MCF-7/ADR cell lines. In vitro study clearly
      illustrated the folate receptor (FR) mediated targeting of FA modified micelles
      to FR-positive human HeLa, KB and MCF-7/ADR cells, while specific delivery to FR
      negative A549 cells was not apparently increased at the same experimental
      conditions. Cytotoxicity assay showed 60% and 58% decrease in IC50 values for
      HeLa and KB cells, while only a slight decrease for A549 cells, following
      treatment with folate modified formulations. The enhanced intracellular delivery
      of FA modified micelles in MCF-7/ADR cells was also observed. In vivo antitumor
      tests revealed DOX entrapped FA-PEOz-PCL micelles effectively inhibited the tumor
      growth and reduced the toxicity to mice compared with free DOX. The current study
      showed that the targeted nano-vector improved cytotoxicity of DOX and suggested
      that this novel PEOz endowed stealthy micelle system held great promise in tumor
      targeted therapy. 

PMID- 24016743
TI  - Latent variable modeling to assist the implementation of Quality-by-Design
      paradigms in pharmaceutical development and manufacturing: a review.
AB  - The introduction of the Quality-by-Design (QbD) initiative and of the Process
      Analytical Technology (PAT) framework by the Food and Drug Administration has
      opened the route to the use of systematic and science-based approaches to support
      pharmaceutical development and manufacturing activities. In this review we
      discuss the role that latent variable models (LVMs) can play in the practical
      implementation of QbD paradigms in the pharmaceutical industry, and the potential
      they may have in assisting the development and manufacturing of new products. The
      ultimate scope is to provide practitioners with a perspective on the
      effectiveness of the use of LVMs in any phase of the development of a
      pharmaceutical product, from its design up to its commercial production. After an
      overview of the main regulatory paradigms the QbD initiative is founded on, we
      show how LVMs can be feasibly used to support pharmaceutical development and
      manufacturing activities while matching the regulatory Agencies' requirements.
      Three main areas are identified, wherein the use of LVMs can provide significant
      benefits: (i) process understanding, (ii) product and process design, and (iii)
      process monitoring and control. For each of them, the main contributions recently
      appeared in the literature are reviewed. Issues open for further research are
      also identified. 

PMID- 24016744
TI  - Use of calcium caseinate in association with lecithin for masking the bitterness
      of acetaminophen--comparative study with sodium caseinate.
AB  - Owing to a variety of structural and functional properties, milk proteins are
      steadily studied for food and pharmaceutical applications. In the present study,
      calcium caseinate in association with lecithin was firstly investigated in order
      to encapsulate the acetaminophen through spray-drying for taste-masking purpose
      for pediatric medicines. A 2(4)-full factorial design revealed that the spray
      flow, the calcium caseinate amount and the lecithin amount had significant
      effects on the release of drug during the first 2 min. Indeed, increasing the
      spray flow and/or the calcium caseinate amount led to increase the released
      amount, whereas increasing the lecithin amount decreased the released amount. The
      "interaction" between the calcium caseinate amount and the lecithin amount was
      also shown to be statistically significant. The second objective was to compare
      the efficiency of two caseinate-based formulations, i.e. sodium caseinate and
      calcium caseinate, on the taste-masking effect. The characteristics of spray
      dried powders determined by SEM and DSC were shown to depend on the
      caseinate/lecithin proportion rather than the type of caseinate. Interestingly,
      calcium caseinate-based formulations were found to lower the released amount of
      drug during the early time to a higher extent than sodium caseinate-based
      formulations, which indicates better taste-masking efficiency.

PMID- 24016746
TI  - Molecular fragment dynamics study on the water-air interface behavior of non
      ionic polyoxyethylene alkyl ether surfactants.
AB  - Molecular fragment dynamics (MFD) is a mesoscopic simulation technique based on
      dissipative particle dynamics (DPD). MFD simulations of the self-aggregation of
      the polyoxyethylene alkyl ether surfactants C6E6, C10E6, C12E6 and C16E6 at the
      water-air surface lead to equilibrium nanoscale structures and computationally
      determined surface tensions which are in agreement with experimental data for
      different surfactant concentrations. Thus, molecular fragment dynamics is a well
      suited predictive technique to study the behavior of new surfactant systems. 

PMID- 24016747
TI  - Kinetic stability and rheology of wax-stabilized water-in-oil emulsions at
      different water cuts.
AB  - The impact of continuous phase wax solidification on the isothermal rheological
      properties of water-in-oil (W/O) emulsions at different water cuts (10-50 wt%)
      was investigated. Rotational viscometry, oscillatory rheology and creep
      compliance and recovery were performed on emulsions aged up to 28 days. Higher
      water cuts yielded emulsions with a higher bulk viscosity and storage modulus
      (G') but lower maximum creep compliance (J(max)) values. The development of a
      more pronounced continuous phase wax crystal network with age led to a
      corresponding increase in emulsion bulk viscosity and G' as well as a decrease in
      Jmax. Supporting results for these findings were acquired with light microscopy,
      solid wax content, and aqueous droplet size analysis. This study established that
      both water cut and continuous phase wax solidification play a significant role in
      W/O emulsion rheology, though this greatly depends on the age of the emulsion.
      Such findings may be used to better understand and tailor emulsion properties in
      fields such as the petrochemical, cosmetics, food and pharmaceutical industries.

PMID- 24016745
TI  - Equivalent neural responses in children and adolescents with and without autism
      during judgments of affect.
AB  - Previous research has noted disrupted patterns of neural activation during
      emotion, processing in individuals with autism spectrum disorders (ASD). However,
      prior research relied on, designs that may place greater cognitive load on
      individuals with ASD. In order to address this issue, we adapted the fMRI task of
      Ochsner et al. (2004a) for children by, presenting fewer stimuli, with fewer
      valence levels, and longer stimuli duration. A localizer sample of, typically
      developing children (n=26) was used to construct regions of interest involved in
      emotional, processing. Activations in these regions during self- and other
      referential emotion processing was, compared in age, IQ, gender matched groups
      (n=17 ASD, n=16 TD). Matched samples replicate, condition contrasts of the
      localizer, but no group differences were found in behavior measures or, neural
      activation. An exploratory functional connectivity analysis in a subset of the
      matched groups, also did not detect striking differences between the groups.
      These findings suggest that disruptions in activation in emotion processing
      neural networks in ASD is partially a function of task related cognitive load. 

PMID- 24016748
TI  - An OA phenotype may obtain major benefit from bone-acting agents.
AB  - BACKGROUND: Osteoarthritis (OA) joints display relevant microstructure
      alterations associated to an increase in remodeling at subchondral bone, which
      supports its crucial role in OA pathogenesis. Despite this, the treatment of knee
      OA patients with antiresorptive drugs has given discordant results, suggesting
      the existence of a particular patient subset with good response to halting high
      subchondral remodeling. OBJECTIVE: To identify an OA phenotype that may obtain
      major benefit from therapy with bone-acting agents. METHODS: A systematic review
      of the literature was performed by searching the Medline and PubMed databases
      from 1990 to April 2013 using the following keywords: subchondral bone, articular
      cartilage, and osteoarthritis in various combinations with bone agents, bone
      mineral density, and scintigraphy. RESULTS: Early animal and human studies
      provided the rationale for the beneficial use of bone agents on OA cartilage
      damage. Several bone-acting agents have reduced low back pain and likely
      spondylosis progression. Recently, strontium ranelate has been reported to exert
      both structural and clinical benefits in knee OA patients with radiological
      progression. However, other antiresorptives have shown divergent results. Human
      studies suggest that these contradictory results may be due to the lack of well
      defined OA phenotypes and an accurate methodology to recruit and follow up these
      patients. CONCLUSIONS: A particular subset of postmenopausal patients with high
      remodeling and/or low subchondral bone density may benefit from the treatment
      with bone-acting agents hindering OA progression. This OA population could be
      identified with the simultaneous use of subchondral bone dual-energy X-ray
      absorptiometry and scintigraphy.

PMID- 24016749
TI  - State-level education standards for substance use prevention programs in schools:
      a systematic content analysis.
AB  - PURPOSE: Three fourths of public schools in the United States maintain
      instructional programs to discourage alcohol, tobacco, and other drug (ATOD) use.
      State-sanctioned instructional standards attempt to direct this ATOD preventive
      education. No existing research, however, systematically codes these standards
      across all grades and states. We performed such an analysis. METHODS: We
      retrieved ATOD standards information from all 50 states and the District of
      Columbia from multiple sources, including the National Association of State
      Boards of Education's State School Health Policy Web site. Three independent
      researchers classified and cross-validated ATOD standards (inter-rater agreement
      = 98%) based on recommended content domains and pedagogic delivery methods.
      RESULTS: We find substantial grade-level variation in standards. Elementary
      schools emphasize generic social skills and affective skills, whereas middle and
      high school standards focus on knowledge about biological and behavioral
      consequences of ATOD use. States also vary widely in their content and coverage
      of standards. Two thirds of states do not include standards in all content areas
      considered "evidence-based." CONCLUSIONS: The ATOD curricular agenda for the
      majority of states falls well below recommended content and delivery benchmarks.
      We intend for our harmonized data set-the first of its kind-to promote research
      that examines the relation among state ATOD standards, actual classroom
      instruction, and adolescent ATOD use.

PMID- 24016750
TI  - Neural stem cells inhibit melanin production by activation of Wnt inhibitors.
AB  - BACKGROUND: Melanin for skin pigmentation is synthesized from tyrosine via an
      enzymatic cascade that is controlled by tyrosinase (TYR), tyrosinase-related
      protein 1 (TRP1), and dopachrome tautomerase/tyrosinase related protein 2
      (Dct/TRP2), which are the targets of microphthalmia-associated transcription
      factor (MITF). MITF is a master regulator of pigmentation and a target of beta
      catenin in Wnt/beta-catenin signaling during melanocyte differentiation. Stem
      cells have been used in skin pigmentation studies, but the mechanisms were not
      determined for the conditioned medium (CM)-mediated effects. OBJECTIVES: In this
      study, the inhibition and mechanisms of melanin synthesis were elucidated in B16
      melanoma cells and UV-B irradiated C57/BL-6 mice that were treated with human
      neural stem cell-conditioned medium (NSC-CM). METHODS: B16-F10 melanoma cells
      (1.5*10(4)cells/well) and the shaved dorsal skin of mice were pretreated with
      various amount (5, 10, 20, 50, and 100%) of NSC-CM. Melanin contents and TYR
      activity were measured by a Spectramax spectrophotometer. The expression of TYR,
      TRP1, Dct/TRP2, MITF, beta-catenin and Wnt inhibitors were evaluated by RT-PCR
      and western blot. The dorsal skin samples were analyzed by immunofluorescence
      with various antibodies and compared with that control of tissues. RESULTS:
      Marked decreases were evident in melanin content and TYR, TRP1, DCT/TRP2, MITF,
      and beta-catenin expression in B16 cells and C57/BL-6 mice. NSC-CM negatively
      regulated Wnt/beta-catenin signaling by decreasing the expression of beta-catenin
      protein, which resulted from robust expression of Wnt inhibitors Dickkopf-1
      (DKK1) and secreted frizzled-related protein 2 (sFRP2). CONCLUSIONS: These
      results demonstrate that NSC-CM suppresses melanin production in vitro and in
      vivo, suggesting that factors in NSC-CM may play an important role in
      deregulation of epidermal melanogenesis.

PMID- 24016751
TI  - [Clinical use of 18F-FDG PET/CT in colorectal carcinoma].
AB  - Modern imaging techniques have an important role in the diagnostic procedures of
      malignancies, and assessing response to therapy. The 18F-FDG PET/CT
      revolutionized the evaluation of colorectal cancer in terms of preoperative
      staging and monitoring of recurrence. Conventional imaging techniques have
      limitations in early assessment of response to therapy. 18F-FDG PET has been
      shown to allow earlier treatment monitoring, because the metabolic change appears
      before any anatomic change occurs. The Response Evaluation Criteria in Solid
      Tumours (RECIST) are widely applied, but they have some limitations. There are
      new international guidelines for treatment response assessment using PET/CT in
      solid tumours. The authors review indications and the role of hybrid PET/CT in
      colorectal cancer.

PMID- 24016752
TI  - [Smoking habits in Hungary: analysis based on surveys of the past decade].
AB  - Passing the amendments to the anti-smoking law in Hungary indicates a firm
      determination of the Department of Health to curb tobacco use. Professional steps
      were destined to follow policies and control measures. The Methodological Support
      Center for Smoking Cessation began operation at the National Koranyi Institute of
      Tuberculosis and Pulmonology, Budapest, Hungary in 2012. The objective is to
      provide methodological assistance for evidence based smoking cessation support.
      The Center aspires to unite and direct the activities aimed at tobacco control,
      as well as initiate the drafting of appropriate medical guidelines. The Center
      works to ensure that information regarding smoking and personalized cessation
      support reaches wide range of Hungarian smokers through individual group and
      telephone counseling methods. Analysis of the results of national surveys
      conducted during the past decade on the adult population reveals that the
      proportion of daily smokers in Hungary has decreased to 28-29%. The proportion of
      men smokers (32-34%) indicates a more significant decrease, while the proportion
      of women smokers (24-25%) levels. Groups that are most affected by increased risk
      of smoking are people with low level of education, those facing economic
      hardship, the age groups of 17-34 and 35-64 years and women.

PMID- 24016753
TI  - [Clinical observations in cutan mastocytosis].
AB  - INTRODUCTION: Mastocytosis is a clonal mast cell proliferative disease, divided
      into cutaneous and systemic forms. The characteristic symptoms are caused by
      neoplastic mast cell infiltrations in different organs and/or the release of
      mediators. AIM: The aim of the authors was to summarize their clinical
      observations in patients with mastocytosis. METHOD: 22 adult patients diagnosed
      consecutively with mastocytosis were enrolled in the study. Skin and bone marrow
      biopsies were taken to establish the diagnosis and perform c-KIT mutation (D816V)
      analysis. RESULTS: One of the 22 patients had teleangiectasia macularis eruptiva
      perstans, while 20/22 patients had urticaria pigmentosa. All patients had
      cutaneous lesions. In 12 patients iliac crest biopsy was performed and 9 of them
      had bone marrow involvement, classified as indolent systemic mastocytosis. The c
      kit mutation D816V was found in one subject both in skin and bone marrow samples.
      The patients were treated with antihistamine, PUVA, interferon-alpha or imatinib.
      CONCLUSIONS: The authors draw attention to this rare disease in order to help
      recognition of relevant signs and symptoms and establish an early diagnosis.

PMID- 24016754
TI  - [Clinical experiences with basal analogue insulin in routine care. Retrospective
      follow up analysis of a database from daily routine care].
AB  - INTRODUCTION: Basal-bolus insulin regime is frequently used in type 2 diabetes in
      order to improve metabolic control and decrease the risk of complications. A
      general question is, however, the effect of application of analogue insulin in
      comparison to human insulin regimes. AIM: The aim of the authors was to perform a
      retrospective database analysis among patients who were switched from human
      insulin only based basal-bolus regime to analogue only insulin regime in order to
      examine changes in metabolic control, body weight, insulin dose and basal:bolus
      insulin ratio. METHOD: Type 2 diabetic patients (n = 137) were enrolled who used
      once daily basal insulin with complementary bolus insulin given at main meals,
      and human insulin was switched to analogue insulin. Patients were divided into
      two groups using detemir (n = 103) or glargine (n = 34). RESULTS: During 17
      months of analogue insulin treatment the HbA1c was decreased by 0.34% (detemir 
      0.44%; glargine -0.17%). Body weight was increased by 1.11 kg (detemir +1.0 kg;
      glargine +1.43 kg). The basal:bolus insulin ratio increased in all groups (entire
      cohort 6.04%, detemir 5.26%, glargine 8.37%). The average insulin dose was 80.76
      units at the end of follow up. There was no significant difference in terms of
      total and basal insulin doses between detemir (27.89 and 79.78 U, respectively)
      and glargine group (32.85 and 83.74 U, respectively). CONCLUSIONS: These results
      support that switching from human to analogue insulin in basal-bolus regime could
      improve the metabolic control by increasing dose of basal analogue insulin and
      basal: bolus ratio. Both detemir and glargine can provide similar improvement in
      metabolic control with the same insulin dose but with relatively more weight gain
      with glargine.

PMID- 24016756
TI  - Pentacene on Ag(111): correlation of bonding distance with intermolecular
      interaction and order.
AB  - We report coverage and temperature dependent bonding distances of vacuum-sublimed
      pentacene (PEN) submonolayers on Ag(111) obtained by the X-ray standing wave
      technique. The average vertical bonding distance of 2.98 A at room temperature
      for 0.50 monolayer (ML) coverage increases to 3.12 A for 0.75 ML due to competing
      intermolecular and adsorbate-substrate interactions. In contrast, decreasing the
      temperature from 295 to 145 K does not impact the bonding distance despite the
      concomitant transition from a "liquidlike" to an ordered molecular arrangement.
      In combination with X-ray photoelectron spectroscopy results, we could identify
      "soft chemisorption" with a subtle balance of molecule-molecule and substrate
      molecule interactions as being responsible for this special adsorption behavior.
      Thus our study sheds light not only on the interface between PEN and Ag(111), but
      also on fundamental adsorption processes of organic adsorbates on metals in the
      context of chemi- and physisorption. 

PMID- 24016757
TI  - Caenorhabditis elegans anillin (ani-1) regulates neuroblast cytokinesis and
      epidermal morphogenesis during embryonic development.
AB  - The formation of tissues is essential for metazoan development. During
      Caenorhabditis elegans embryogenesis, ventral epidermal cells migrate to encase
      the ventral surface of the embryo in a layer of epidermis by a process known as
      ventral enclosure. This process is regulated by guidance cues secreted by the
      underlying neuroblasts. However, since the cues and their receptors are
      differentially expressed in multiple cell types, the role of the neuroblasts in
      ventral enclosure is not fully understood. Furthermore, although F-actin is
      required for epidermal cell migration, it is not known if nonmuscle myosin is
      also required. Anillin (ANI-1) is an actin and myosin-binding protein that
      coordinates actin-myosin contractility in the early embryo. Here, we show that
      ANI-1 localizes to the cleavage furrows of dividing neuroblasts during mid
      embryogenesis and is required for their division. Embryos depleted of ani-1
      display a range of ventral enclosure phenotypes, where ventral epidermal cells
      migrate with similar speeds to control embryos, but contralateral neighbors often
      fail to meet and are misaligned. The ventral enclosure phenotypes in ani-1 RNAi
      embryos suggest that the position or shape of neuroblasts is important for
      directing ventral epidermal cell migration, although does not rule out an
      autonomous requirement for ani-1 in the epidermal cells. Furthermore, we show
      that rho-1 and other regulators of nonmuscle myosin activity are required for
      ventral epidermal cell migration. Interestingly, altering nonmuscle myosin
      contractility alleviates or strengthens ani-1's ventral enclosure phenotypes. Our
      findings suggest that ventral enclosure is a complex process that likely relies
      on inputs from multiple tissues. 

PMID- 24016758
TI  - Direct activation of a mouse Hoxd11 axial expression enhancer by Gdf11/Smad
      signalling.
AB  - A Hoxd11/lacZ reporter, expressed with a Hoxd11-like axial expression pattern in
      transgenic mouse embryos, is stimulated in tailbud fragments when cultured in
      presence of Gdf11, a TGF-beta growth/differentiation factor. The same construct
      is also stimulated by Gdf11 when transiently transfected into cultures of HepG2
      cells. Stimulation of the reporter in HepG2 cells is enhanced where it contains
      only the 332 bp Hoxd11 enhancer region VIII upstream or downstream of a
      luciferase or lacZ reporter. This enhancer contains three elements conserved from
      fish to mice, one of which has the sequence of a Smad3/4 binding element.
      Mutation of this motif inhibits the ability of Gdf11 to enhance reporter activity
      in the HepG2 cell assay. Chromatin immunoprecipitation experiments show direct
      evidence of Smad2/3 protein binding to the Hoxd11 region VIII enhancer. The
      action of Gdf11 upon Hoxd11 in HepG2 cells is inhibited, at least in part, by
      SIS3, a specific inhibitor of Smad3. SIS3 also produces partial inhibition of
      Hoxd11/lacZ expression in cultured transgenic tailbuds, indicating that Smad3 may
      play a similar role in the embryonic expression of Hoxd11. Transgenic mouse
      experiments show that the Smad binding motif is essential for the axial
      expression of Hoxd11/lacZ reporter in the embryo tailbud, posterior mesoderm and
      neurectoderm. 

PMID- 24016760
TI  - Novel percutaneous femoral arterial-transthoracic approach for closure of
      ascending aortic pseudoaneurysm with a septal occluder device in a child.
AB  - Ascending aortic pseudoaneurysms are a rare complication following cardiac
      surgery. Their traditional surgical management carries high morbidity and
      mortality, especially in patients with multiple comorbidities. Transcatheter
      closure of these pseudoaneurysms using a septal occluder device has been
      previously reported in adults as an alternative approach with fewer
      complications. We report the first case of a novel percutaneous femoral arterial
      transthoracic approach for exclusion of an ascending aortic pseudoaneurysm with
      an Amplatzer atrial septal occluder device in a 9-year-old child with Takayasu's
      arteritis. 

PMID- 24016759
TI  - Tbx18 regulates development of the epicardium and coronary vessels.
AB  - The epicardium and coronary vessels originate from progenitor cells in the
      proepicardium. Here we show that Tbx18, a T-box family member highly expressed in
      the proepicardium, controls critical early steps in coronary development. In
      Tbx18(-/-) mouse embryos, both the epicardium and coronary vessels exhibit
      structural and functional defects. At E12.5, the Tbx18-deficient epicardium
      contains protrusions and cyst-like structures overlying a disorganized coronary
      vascular plexus that contains ectopic structures resembling blood islands. At
      E13.5, the left and right coronary stems form correctly in mutant hearts.
      However, analysis of PECAM-1 whole mount immunostaining, distribution of
      SM22alpha(lacZ/+) activity, and analysis of coronary vascular casts suggest that
      defective vascular plexus remodeling produces a compromised arterial network at
      birth consisting of fewer distributing conduit arteries with smaller lumens and a
      reduced capacity to conduct blood flow. Gene expression profiles of Tbx18(-/-)
      hearts at E12.5 reveal altered expression of 79 genes that are associated with
      development of the vascular system including sonic hedgehog signaling components
      patched and smoothened, VEGF-A, angiopoietin-1, endoglin, and Wnt factors
      compared to wild type hearts. Thus, formation of coronary vasculature is
      responsive to Tbx18-dependent gene targets in the epicardium, and a poorly
      structured network of coronary conduit vessels is formed in Tbx18 null hearts due
      to defects in epicardial cell signaling and fate during heart development.
      Lastly, we demonstrate that Tbx18 possesses a SRF/CArG box dependent repressor
      activity capable of inhibiting progenitor cell differentiation into smooth muscle
      cells, suggesting a potential function of Tbx18 in maintaining the progenitor
      status of epicardial-derived cells. 

PMID- 24016761
TI  - A nutrition survey in four South East Asian countries. Preface.

PMID- 24016762
TI  - Food consumption and nutritional and biochemical status of 0.5-12-year-old
      Indonesian children: the SEANUTS study.
AB  - Indonesia is currently facing the double burden of malnutrition. While
      undernutrition is still a major public health problem, the prevalence of
      overnutrition is increasing. The objective of the South East Asian Nutrition
      Survey (SEANUTS) was to provide up-to-date data on nutritional status, food
      consumption and biochemical parameters related to nutrition for children aged 0.5
      12 years. The SEANUTS study in Indonesia was conducted in a nationwide
      representative sample of 7.211 children using multistage cluster sampling based
      on probability proportional to size, stratified for geographical location, in
      forty-eight out of 440 districts/cities. The results show that the growth (weight
      for age, height for age, weight for height and BMI for age) of Indonesian pre
      school- and school-aged children is below the WHO standards. The older the
      children, the more the deviation from the WHO standard curves. Underweight was
      more prevalent in rural areas (28.9 v. 19.2%) and overweight/obesity was observed
      to be more widespread in urban areas (5.6 v. 3.2%). The prevalence varied with
      age groups and sexes. The overall prevalence of stunting was 25.2 and 39.2% in
      urban and rural areas, respectively. The prevalence of anaemia was nearly 55% in
      children aged 0.5-1.9 years and ranged from 10.6 to 15.5% in children aged 2-12
      years. Fe deficiency was observed in 4.1-8.8% of the children. The percentage of
      children with dietary intakes of energy, protein, and vitamins A and C below the
      Indonesian RDA was high and differed across urban and rural areas and age groups.

PMID- 24016763
TI  - Design of the South East Asian Nutrition Survey (SEANUTS): a four-country
      multistage cluster design study.
AB  - Nutrition is a well-known factor in the growth, health and development of
      children. It is also acknowledged that worldwide many people have dietary
      imbalances resulting in over- or undernutrition. In 2009, the multinational food
      company FrieslandCampina initiated the South East Asian Nutrition Survey
      (SEANUTS), a combination of surveys carried out in Indonesia, Malaysia, Thailand
      and Vietnam, to get a better insight into these imbalances. The present study
      describes the general study design and methodology, as well as some problems and
      pitfalls encountered. In each of these countries, participants in the age range
      of 0.5-12 years were recruited according to a multistage cluster randomised or
      stratified random sampling methodology. Field teams took care of recruitment and
      data collection. For the health status of children, growth and body composition,
      physical activity, bone density, and development and cognition were measured. For
      nutrition, food intake and food habits were assessed by questionnaires, whereas
      in subpopulations blood and urine samples were collected to measure the
      biochemical status parameters of Fe, vitamins A and D, and DHA. In Thailand, the
      researchers additionally studied the lipid profile in blood, whereas in Indonesia
      iodine excretion in urine was analysed. Biochemical data were analysed in
      certified laboratories. Study protocols and methodology were aligned where
      practically possible. In December 2011, data collection was finalised. In total,
      16,744 children participated in the present study. Information that will be very
      relevant for formulating nutritional health policies, as well as for designing
      innovative food and nutrition research and development programmes, has become
      available.

PMID- 24016764
TI  - Nutritional status and dietary intakes of children aged 6 months to 12 years:
      findings of the Nutrition Survey of Malaysian Children (SEANUTS Malaysia).
AB  - The dual burden of malnutrition reportedly coexists in Malaysia; however,
      existing data are scarce and do not adequately represent the nutritional status
      of Malaysian children. The Nutrition Survey of Malaysian Children was carried out
      with the aim of assessing the nutritional status in a sample of nationally
      representative population of children aged 6 months to 12 years. A total of 3542
      children were recruited using a stratified random sampling method. Anthropometric
      measurements included weight, height, mid-upper arm circumference, and waist and
      hip circumferences. Blood biochemical assessment involved analyses of Hb, serum
      ferritin, and vitamins A and D. Dietary intake was assessed using semi
      quantitative FFQ, and nutrient intakes were compared with the Malaysian
      Recommended Nutrient Intakes (RNI). The prevalence of overweight (9.8%) and
      obesity (11.8%) was higher than that of thinness (5.4%) and stunting (8.4%). Only
      a small proportion of children had low levels of Hb (6.6%), serum ferritin (4.4%)
      and vitamin A (4.4%), but almost half the children (47.5%) had vitamin D
      insufficiency. Dietary intake of the children was not compatible with the
      recommendations, where more than one-third did not achieve the Malaysian RNI for
      energy, Ca and vitamin D. The present study revealed that overnutrition was more
      prevalent than undernutrition. The presence of high prevalence of vitamin D
      insufficiency and the inadequate intake of Ca and vitamin D are of concern.
      Hence, strategies for improving the nutritional status of Malaysian children need
      to consider both sides of malnutrition and also put emphasis on approaches for
      the prevention of overweight and obesity as well as vitamin D insufficiency.

PMID- 24016765
TI  - SEANUTS: the nutritional status and dietary intakes of 0.5-12-year-old Thai
      children.
AB  - In the present study, we investigated nutritional status and health-related
      factors in a multistage cluster sample of 3119 Thai urban and rural children aged
      0.5-12.9 years. In a subsample, blood samples were collected for the measurement
      of Hb, transferrin receptor, vitamin A and vitamin D concentrations. The
      prevalence of stunting and underweight was higher in rural children than in urban
      children, whereas the wasting rate was similar in both rural and urban areas.
      Among children aged 3.0-5.9 years, the prevalence of overweight was significantly
      higher in urban areas than in rural areas and so was the obesity rate in children
      aged 6.0-12.9 years. Protein intakes of all age groups were relatively high in
      both the areas. Intakes of Ca, Fe, Zn and vitamin C were significantly higher in
      urban areas than in rural areas. The prevalence of anaemia in rural areas was
      twice as high as that in urban areas, particularly in infants and young children.
      However, the prevalence of Fe-deficiency anaemia was similar in both urban and
      rural areas. While the prevalence of vitamin A deficiency (by serum retinol cut
      off < 0.7 MUmol/l) seemed to be very low, vitamin A insufficiency (by serum
      retinol cut-off < 1.05 MUmol/l) was more prevalent (29.4-31.7%) in both the
      areas. The prevalence of vitamin D insufficiency ranged between 27.7 and 45.6%
      among the children. The present study indicates that the double burden of
      malnutrition is still a major public health problem in Thailand. Further studies
      need to explore the associated risk factors for these nutrient deficiencies.
      Effective strategies and actions are needed to tackle the nutritional problems in
      Thai children.

PMID- 24016766
TI  - Double burden of undernutrition and overnutrition in Vietnam in 2011: results of
      the SEANUTS study in 0.5-11-year-old children.
AB  - The Vietnamese South East Asian Nutrition Survey (SEANUTS), a cross-sectional
      study, was undertaken to assess the nutritional status in a nationally
      representative sample of children aged 0.5-11.9 years. A multi-stage cluster
      randomised sampling method was used to recruit 2872 children. Anthropometric
      measurements included weight, height, mid-upper arm circumference, and waist and
      hip circumferences. Blood biochemistry involved analyses of Hb, serum ferritin,
      and vitamins A and D. Dietary intake was assessed using a 24 h recall
      questionnaire, and nutrient intakes were compared with the Vietnamese RDA. In
      children aged < 5 years, approximately 14% were stunted, 8.6% underweight and
      4.4% thin. A higher prevalence of stunting (15.6%) and underweight (22.2%) was
      observed in school-aged children. Undernutrition was more prevalent in rural
      areas than in urban areas. In contrast, almost 29% of the urban children were
      either overweight or obese when compared with 4% of the overweight children and
      1.6% of the obese children in rural areas. A higher percentage of children in the
      age group 0.5-1.9 years and residing in rural areas had low Hb levels than those
      in the age group 2.0-5.9 years and residing in urban areas. In children aged 6-11
      years, a small percentage had low Hb (11-14%) and vitamin A (5-10%) levels, but
      almost half the children (48-53%) had vitamin D insufficiency. Food consumption
      data indicated that the children did not meet the RDA for energy, protein, Fe,
      vitamin A, vitamin B1 and vitamin C. Results from the SEANUTS highlight the
      double burden of malnutrition in Vietnam. Information from the SEANUTS can serve
      as an input for targeted policy development, planning and development of
      nutrition programmes.

PMID- 24016767
TI  - Relationship between anthropometric indicators and cognitive performance in
      Southeast Asian school-aged children.
AB  - Nutrition is an important factor in mental development and, as a consequence, in
      cognitive performance. Malnutrition is reflected in children's weight, height and
      BMI curves. The present cross-sectional study aimed to evaluate the association
      between anthropometric indices and cognitive performance in 6746 school-aged
      children (aged 6-12 years) of four Southeast Asian countries: Indonesia;
      Malaysia; Thailand; Vietnam. Cognitive performance (non-verbal intelligence
      quotient (IQ)) was measured using Raven's Progressive Matrices test or Test of
      Non-Verbal Intelligence, third edition (TONI-3). Height-for-age z-scores (HAZ),
      weight-for-age z-scores (WAZ) and BMI-for-age z-scores (BAZ) were used as
      anthropometric nutritional status indices. Data were weighted using age, sex and
      urban/rural weight factors to resemble the total primary school-aged population
      per country. Overall, 21% of the children in the four countries were underweight
      and 19% were stunted. Children with low WAZ were 3.5 times more likely to have a
      non-verbal IQ < 89 (OR 3.53 and 95% CI 3.52, 3.54). The chance of having a non
      verbal IQ < 89 was also doubled with low BAZ and HAZ. In contrast, except for
      severe obesity, the relationship between high BAZ and IQ was less clear and
      differed per country. The odds of having non-verbal IQ levels < 89 also increased
      with severe obesity. In conclusion, undernourishment and non-verbal IQ are
      significantly associated in 6-12-year-old children. Effective strategies to
      improve nutrition in preschoolers and school-aged children can have a pronounced
      effect on cognition and, in the longer term, help in positively contributing to
      individual and national development.

PMID- 24016768
TI  - Susceptibility of gram-negative aerobic bacilli from intra-abdominal pathogens to
      antimicrobial agents collected in the United States during 2011.
AB  - OBJECTIVES: During 2011, a total of 1442 gram-negative pathogens from intra
      abdominal infections were collected as part of the Study for Monitoring
      Antimicrobial Resistance Trends (SMART) from 19 hospital sites within the United
      States. Susceptibility to ertapenem and comparators and molecular analysis of
      ertapenem resistant isolates was performed. METHODS: Extended-spectrum beta
      lactamase ESBL (ESBL) isolates were determined using the Clinical and Laboratory
      Standards Institute's recommended phenotypic test. Isolates were identified to
      the species level, and tested for antimicrobial susceptibility using custom
      MicroScan dehydrated broth microdilution panels ESBLs and carbapenemases were
      characterized using the Check-Points microarray. Strain typing of Klebsiella
      pneumoniae was performed by rep-PCR on the DiversiLab System. RESULTS: The
      majority of isolates were Escherichia coli (36%), K. pneumoniae (18.6%),
      Pseudomonas aeruginosa (12.1%) and Enterobacter cloacae (8.4%). Incidence of ESBL
      positive isolates was 12.7%, 9.7%, 3.6% and 3.1% for K. pneumoniae, E. coli,
      Proteus mirabilis and Klebsiella oxytoca, respectively. Against the majority of
      isolates and species tested, the most active antibiotics were amikacin,
      ertapenem, and imipenem, with the carbapenems being the most active in vitro,
      including against ESBL-positive isolates of E. coli. All other antibiotics
      exhibited diminished activity. Against K. pneumoniae, the carbapenems were
      notably less active against ESBL-positive isolates though their activity against
      this sub-population was still the highest of all antibiotics tested; however,
      41.1% (14 of 34) of the phenotypically ESBL-positive K. pneumoniae co-produced a
      carbapenemase (KPC2 or KPC3), and >90% of the isolates producing only an ESBL
      remained susceptible to ertapenem. CONCLUSIONS: Further monitoring of
      susceptibility of intra-abdominal isolates is warranted due to limited
      therapeutic options available to physicians.

PMID- 24016769
TI  - [Gardnerella vaginalis bacteremia in a male patient].

PMID- 24016770
TI  - Knowledge, attitudes, and beliefs of French medical students about antibiotic
      prescribing and resistance.
AB  - OBJECTIVES: We had for aim to learn about medical students' knowledge and
      perspectives on antibiotic prescribing and bacterial resistance. METHODS:
      Penultimate and final year students at a French medical school were invited to
      participate in an anonymous online survey in summer 2012. RESULTS: The response
      rate was 20% (60/297). Penultimate and final year students gave similar answers.
      Students felt more confident in diagnosing an infection, and less confident in
      choosing the correct dose and interval of antibiotic administration. Seventy-nine
      percent of students wanted more training on antibiotic treatments. Sixty-nine
      percent of students knew that antibiotic prescriptions were inappropriate or
      unnecessary in 21-60% of the cases, and 95% believed that these prescriptions
      were unethical. Only 27% knew that more than 80% of antibiotic prescriptions were
      made in community practice. Students believed that the most important causes of
      resistance were that too many prescriptions were made and broad-spectrum
      antibiotic use; 27% believed poor hand hygiene was "not at all important". Ninety
      four percent believed resistance was a national problem, and 69% mentioned it as
      a problem in their hospital. Sixty-three percent thought that the antibiotics
      they would prescribe would contribute to resistance, and 96% thought resistance
      would be a greater problem in the future. Twenty-two percent knew MRSA bacteremia
      rates had decreased over the past decade in France. CONCLUSIONS: Medical students
      are aware that antibiotic resistance is a current and growing problem. They would
      like more training on antibiotic selection.

PMID- 24016771
TI  - Endocarditis and spondylodiscitis due to Neisseria elongata subsp. nitroreducens.

PMID- 24016772
TI  - Blood pressure monitoring is better at home.

PMID- 24016773
TI  - Understanding the gap between need and utilization in outpatient care--the effect
      of supply-side determinants on regional inequities.
AB  - The present study analyzes the effect of supply-side determinants on regional
      inequities in outpatient care. Inequities are measured by the degree of disparity
      between need for and actual utilization of outpatient health services in the 412
      German districts. Outpatient care needs of each district are determined by
      applying the regression model of the German risk structure compensation scheme.
      We find that supply-side factors account for half of the model's coverage of
      regional inequities. The remaining regional variance explained by the model may
      be attributed to socioeconomic and (socio-)geographic determinants as well as
      price effects. Our findings call for strengthening the role of GPs as
      coordinators in the health care system, countering the geographic maldistribution
      of physicians and introducing adequate programs to improve the level of care in
      socially deprived districts. The study also highlights the importance of
      differentiating between need, demand and utilization of health services in order
      to understand the root causes of inequities. 

PMID- 24016775
TI  - Amyloid beta(1-42) in aqueous environments: effects of ionic strength and E22Q
      (Dutch) mutation.
AB  - Development of extracellular plaques characteristic of Alzheimer's disease is
      related to aggregation of amyloid peptides. The Abeta-42 peptide is the most
      aggregation prone species, and some missense mutant forms increase this
      aggregation ability. Due to its poor solubility as monomer in aqueous solutions,
      Abeta-42 conformational transitions in water have been largely investigated by
      molecular dynamics. Here we report an all-atom molecular dynamics analysis of the
      Abeta-42 peptide in aqueous environment using as starting conformation a
      structure obtained in an isotropic, low-polarity medium, representing a plausible
      model for the membrane-bound species. While previous studies commonly show that
      Abeta-42 is largely unstructured in aqueous solution, here we report that this
      peptide can adopt partially folded structures. Importance of ionic strength has
      been also investigated, showing that at physiological ionic strength condition a
      loop stabilizing electrostatic interaction involving Lys28 builds up. In
      addition, besides stable alpha-helix structures, we observe the appearance of 310
      helix, similar to what was reported experimentally for the Abeta-40 species. The
      effect of E22Q (Dutch) mutation in high ionic strength condition has been
      explored. We show that this mutation has a dramatic impact on the Abeta-42
      structure. Instead of a partially folded, but extended, conformation obtained
      with the wild type, the E22Q assumes a two-helix collapsed one due to the
      clustering of hydrophobic residues. 

PMID- 24016774
TI  - Flavodoxin cofactor binding induces structural changes that are required for
      protein-protein interactions with NADP(+) oxidoreductase and pyruvate formate
      lyase activating enzyme.
AB  - Flavodoxin (Fld) conformational changes, thermal stability, and cofactor binding
      were studied using circular dichroism (CD), isothermal titration calorimetry
      (ITC), and limited proteolysis. Thermodynamics of apo and holo-Fld folding were
      examined to discern the features of this important electron transfer protein and
      to provide data on apo-Fld. With the exception of fluorescence and UV-vis binding
      experiments with its cofactor flavin mononucleotide (FMN), apo-Fld is almost
      completely uncharacterized in Escherichia coli. Fld is more structured when the
      FMN cofactor is bound; the association is tight and driven by enthalpy of
      binding. Surface plasmon resonance binding experiments were carried out under
      anaerobic conditions for both apo- and holo-Fld and demonstrate the importance of
      structure and conformation for the interaction with binding partners. Holo-Fld is
      capable of associating with NADP(+)-dependent flavodoxin oxidoreductase (FNR) and
      pyruvate formate-lyase activating enzyme (PFL-AE) whereas there is no detectable
      interaction between apo-Fld and either protein. Limited proteolysis experiments
      were analyzed by LC-MS to identify the regions in Fld that are involved in
      conformation changes upon cofactor binding. Docking software was used to model
      the Fld/PFL-AE complex to understand the interactions between these two proteins
      and gain insight into electron transfer reactions from Fld to PFL-AE. 

PMID- 24016777
TI  - Hepatitis B antivirals and resistance.
AB  - Antiviral therapy for chronic hepatitis B (CHB) has improved the outcome of
      patients. However, due to the multiple selection pressures of different
      nucleos(t)ide analogue, drug resistant HBV variants have emerged. Because of the
      arrangement of overlapping reading frames in HBV genome, these variants not only
      have clinical implications such as drug resistance, but also the potential to
      pose public health issues via vaccine escape. Whilst emergence of these variants
      cannot be prevented, careful selection and institution of the appropriate rescue
      anti viral therapy based on high genetic barrier and high potency should minimize
      this outcome. 

PMID- 24016776
TI  - Paradoxical roles of autophagy in different stages of tumorigenesis: protector
      for normal or cancer cells.
AB  - Autophagy serves as a dynamic degradation and recycling system that provides
      biological materials and energy in response to stress. The role of autophagy in
      tumor development is complex. Various studies suggest that autophagy mainly
      contributes to tumor suppression during the early stage of tumorigenesis and
      tumor promotion during the late stage of tumorigenesis. During the tumorization
      of normal cells, autophagy protects genomic stability by retarding stem cells
      involved damage/repair cycle, and inhibits the formation of chronic inflammatory
      microenvironment, thus protecting normal cell homeostasis and preventing tumor
      generation. On the other hand, autophagy also protects tumor cells survival
      during malignant progression by supporting cellular metabolic demands, decreasing
      metabolic damage and supporting anoikis resistance and dormancy. Taken together,
      autophagy appears to play a role as a protector for either normal or tumor cells
      during the early or late stage of tumorigenesis, respectively. The process of
      tumorigenesis perhaps needs to undergo twice autophagy-associated screening. The
      normal cells that have lower autophagy capacity are prone to tumorization, and
      the incipient tumor cells that have higher autophagy capacity possibly are easier
      to survival in the hash microenvironment and accumulate more mutations to promote
      malignant progression. 

PMID- 24016778
TI  - Immunohistochemical evidence for myofibroblast-like cells associated with liver
      injury induced by aflatoxin B1 in rainbow trout (Oncorhynchus mykiss).
AB  - In mammalian species, profibrogenic cells are activated to become myofibroblasts
      in response to liver damage. Few studies have examined hepatic myofibroblasts and
      their role in liver damage in teleosts. The aim of the present study was to
      investigate the involvement of myofibroblast-like cells in rainbow trout
      (Oncorhynchus mykiss) with hepatic damage induced by aflatoxin B1 (AFB1).
      Histopathological and immunohistochemical analyses characterized alterations in
      the liver stroma during the carcinogenic process. Anti-human alpha-smooth muscle
      actin (SMA) and anti-human desmin primary antibodies were used in
      immunohistochemistry. Only the anti-SMA reagent labelled cells in trout liver. In
      the livers of control fish, only smooth muscle in blood vessels and around bile
      ducts was labelled. In the livers from AFB1-treated fish, SMA-positive cells were
      present in the stroma surrounding neoplastic lesions and in areas of desmoplastic
      reaction. These observations indicate that in teleosts, as in mammals, the
      myofibroblast-like cell is involved in fibrosis associated with liver injury.
      Chronic liver injury induced in trout by aflatoxin may provide a useful model
      system for study of the evolution of such mechanisms. 

PMID- 24016779
TI  - Pathology and localization of Avibacterium endocarditidis in experimentally
      infected broiler breeders.
AB  - The aim of this study was to investigate the pathogenic potential of Avibacterium
      endocarditidis. Forty broiler breeders were inoculated with one of three doses of
      the organism and killed at different time points. Bacteriology, pathology and
      fluorescence in-situ hybridization (FISH) were performed to evaluate bacterial
      growth and the development of lesions. Abundant growth in pure culture of A.
      endocarditidis was always obtained from valvular lesions, while only poor growth
      or no growth was obtained from liver and spleen lesions, confirming previous
      observations from naturally occurring cases. Gross lesions and histopathological
      findings confirmed previous observations. Valvular lesions were acute, ranging
      from slight thickening of the valves to severe inflammation. In most cases,
      bacteria colonized the valves. Lesions observed in the spleen included different
      degrees of necrosis and liver lesions ranged from very small infarcts to large
      areas of coagulative necrosis. Arthritis occurred in 19 birds, 15 of which tested
      positive for A. endocarditidis. Most birds developed bacteraemia, but the
      inability to isolate bacteria from the liver and spleen and the lack of bacteria
      demonstrated by FISH and histopathology, suggested lack of fulminant septicaemia.
      A significant correlation between the size of dose inoculated and development of
      valvular endocarditis was not observed; however, regressive changes in the ovary,
      liver necrosis and hepato-, spleno- and renomegaly were significantly dose
      dependent. A. endocarditidis represents a potential pathogen for chickens, the
      reservoir of which remains to be determined.

PMID- 24016780
TI  - Oral papillary squamous cell carcinoma in twelve dogs.
AB  - Papillary squamous cell carcinoma (PSCC) is a distinct histological subtype of
      oral squamous cell carcinoma (SCC), described in both dogs and man. In dogs, PSCC
      has long been considered a malignant oral tumour of very young animals, but it
      has recently been reported to occur in adult dogs as well. The aim of this study
      was to describe the major clinicopathological characteristics of canine oral PSCC
      (COPSCC). Twelve dogs diagnosed with COPSCC were included in this retrospective
      study (1990-2012). The majority (75%) of the dogs were >6 years of age (median
      age 9 years). All tumours were derived from the gingiva of dentate jaws, with
      66.7% affecting the rostral aspects of the jaws. The gross appearance of the
      lesions varied, with one having an intraosseous component only. The majority
      (91.7%) of the tumours were advanced lesions (T2 and T3), but no local or distant
      metastases were noted. Microscopically, two patterns were seen: (1) invasion of
      bone forming a cup-shaped indentation in the bone or a deeply cavitating cyst
      within the bone (cavitating pattern), (2) histologically malignant growth, but
      lack of apparent bone invasion (non-cavitating pattern). The microscopical
      appearance corresponded to imaging findings in a majority of cases, with
      cavitating forms presenting with a cyst-like pattern of bone loss or an expansile
      mass on imaging and non-cavitating forms showing an infiltrative pattern of bone
      destruction on imaging. These features suggest two distinct biological behaviours
      of COPSCC.

PMID- 24016781
TI  - Optimization of an immunohistochemical method to assess distribution of tight
      junction proteins in canine epidermis and adnexae.
AB  - Epidermal tight junctions (TJs) have been well characterized in human medicine.
      Abnormality of these structures is involved in skin diseases such as atopic
      dermatitis. There is little information about the expression and distribution of
      TJ proteins in the canine skin. The aim of this study was to develop an optimal
      immunohistochemical method for assessment of the expression of TJ proteins in the
      skin of healthy dogs. Formalin-fixed and paraffin wax-embedded skin biopsy
      samples from healthy human and canine patients were used. Canine skin samples
      were from the inguinal region and the nasal planum. Immunohistochemistry was used
      to study the expression of zonula occludens-1 (ZO-1), occludin and claudin-1, -4
      and -7. Heat-induced antigen retrieval with EDTA (pH 9.0) yielded the best
      labelling of TJ proteins. ZO-1 and occludin were expressed in the cytoplasm and
      along the keratinocyte membrane, while claudin-1 and -4 were mainly membrane in
      distribution. ZO-1, occludin and claudin-1 were detected in all epidermal layers
      with the exception of the stratum corneum, while claudin-4 expression was
      restricted to the stratum granulosum. Expression of claudin-7 was difficult to
      evaluate. There was no difference in labelling pattern between inguinal and nasal
      planum skin.

PMID- 24016782
TI  - Spontaneously arising concurrent ileocaecal adenocarcinoma and renal pelvis
      transitional cell carcinoma in a rhesus macaque (Macaca mulatta).
AB  - A 25-year-old, female rhesus macaque (Macaca mulatta) presented with a history of
      weight loss despite a normal appetite and supportive care. The animal was
      humanely destroyed due to poor prognosis. Post-mortem examination revealed a
      focally extensive, firm, white annular constriction at the ileocaecal junction
      and an incidental finding of a pale white nodule approximately 0.8 cm in diameter
      in the left renal pelvis. Based on the microscopical findings, ileocaecal
      adenocarcinoma and renal pelvis transitional cell carcinoma (TCC) were diagnosed.
      The use of cytokeratin (CK)-7 and -20 and uroplakin III as potential renal TCC
      markers was evaluated. The neoplastic cells were labelled intensely with
      antibodies to uroplakin III, but not to CK-7 or -20. Spontaneous intestinal
      adenocarcinoma has been documented in the rhesus macaque, but concurrent renal
      pelvis TCC is highly unusual.

PMID- 24016783
TI  - Characterization of post transplantation lymphoma in feline renal transplant
      recipients.
AB  - The development of malignant neoplasia following solid organ transplantation and
      immunosuppression is well recognized in man. Post-transplantation malignant
      tumours include non-melanoma skin cancers, non-Hodgkin's lymphoma and Kaposi's
      sarcoma and many of these cancers have a known or suspected viral cause. A
      similar increased incidence of cancer is seen in cats that have received a renal
      transplant and lymphoma is the predominant neoplasm in this population. This
      study examines a population of cats that received renal transplants at the
      University of Pennsylvania School of Veterinary Medicine and subsequently
      developed neoplasia. From 1998 to 2010, 111 cats were transplanted and 25 cats
      developed cancer (22.5%). Fourteen of the 25 cats were diagnosed with lymphoma
      (56%), making it the most common tumour in this patient population. The median
      interval between transplantation and diagnosis of lymphoma was 617 days and the
      median survival time (MST) following the diagnosis of lymphoma was 2 days.
      Tissues from seven of these cats were available for histopathological review as
      either samples collected at necropsy examination (n = 5) or biopsy submissions (n
      = 2). Five of these cats had multiorgan involvement with sites including the
      liver, spleen, peripheral and mesenteric lymph nodes, small intestine, urinary
      bladder, heart, mesenteric fat and body wall. Four of the cats with multiorgan
      disease had involvement of the renal allograft two of which also had lymphoma of
      the native kidney. All lymphomas were classified as mid to high grade, diffuse
      large B-cell lymphoma, which is also the most common lymphoma subtype in human
      cases of post-transplantation lymphoproliferative disorders.

PMID- 24016784
TI  - Cutaneous squamous cell carcinoma presenting as a wound with discharging sinus
      tracts in a wild African lion (Panthera leo).
AB  - A female wild African lion (Panthera leo) was presented with an 8-month history
      of a wound with multiple discharging sinus tracts on the left paw. Microscopical
      examination revealed squamous cell carcinoma (SCC). To the best of our knowledge,
      this is the first report of cutaneous SCC in an African lion. Cutaneous SCC
      presenting as discharging sinus tracts lined by neoplastic squamous cells has not
      been reported previously in animals. 

PMID- 24016785
TI  - Bias and learning in temporal binding: intervals between actions and outcomes are
      compressed by prior bias.
AB  - It has consistently been shown that agents judge the intervals between their
      actions and outcomes as compressed in time, an effect named intentional binding.
      In the present work, we investigated whether this effect is result of prior bias
      volunteers have about the timing of the consequences of their actions, or if it
      is due to learning that occurs during the experimental session. Volunteers made
      temporal estimates of the interval between their action and target onset (Action
      conditions), or between two events (No-Action conditions). Our results show that
      temporal estimates become shorter throughout each experimental block in both
      conditions. Moreover, we found that observers judged intervals between action and
      outcomes as shorter even in very early trials of each block. To quantify the
      decrease of temporal judgments in experimental blocks, exponential functions were
      fitted to participants' temporal judgments. The fitted parameters suggest that
      observers had different prior biases as to intervals between events in which
      action was involved. These findings suggest that prior bias might play a more
      important role in this effect than calibration-type learning processes. 

PMID- 24016787
TI  - US Pharmacopeia fighting counterfeit medicines in Africa.

PMID- 24016786
TI  - New antiplatelet agents for cardiovascular disease.

PMID- 24016788
TI  - Wernicke encephalopathy: a medical emergency.

PMID- 24016790
TI  - It's time to put maternal suicide under the microscope.

PMID- 24016791
TI  - New drug targets resistant tuberculosis.

PMID- 24016792
TI  - Food donations: a cultural health conundrum.

PMID- 24016793
TI  - Rare recovery for acid attack victim in Cambodia.

PMID- 24016794
TI  - Utility of prior screening for methicillin-resistant Staphylococcus aureus in
      predicting resistance of S. aureus infections.
AB  - BACKGROUND: Screening for methicillin-resistant Staphylococcus aureus (MRSA) is
      intended to reduce nosocomial spread by identifying patients colonized by MRSA.
      Given the widespread use of this screening, we evaluated its potential clinical
      utility in predicting the resistance of clinical isolates of S. aureus. METHODS:
      We conducted a 2-year retrospective cohort study that included patients with
      documented clinical infection with S. aureus and prior screening for MRSA. We
      determined test characteristics, including sensitivity and specificity, of
      screening for predicting the resistance of subsequent S. aureus isolates.
      RESULTS: Of 510 patients included in the study, 53 (10%) had positive results
      from MRSA screening, and 79 (15%) of infecting isolates were resistant to
      methicillin. Screening for MRSA predicted methicillin resistance of the infecting
      isolate with 99% (95% confidence interval [CI] 98%-100%) specificity and 63% (95%
      CI 52%-74%) sensitivity. When screening swabs were obtained within 48 hours
      before isolate collection, sensitivity increased to 91% (95% CI 71%-99%) and
      specificity was 100% (95% CI 97%-100%), yielding a negative likelihood ratio of
      0.09 (95% CI 0.01-0.3) and a negative predictive value of 98% (95% CI 95%-100%).
      The time between swab and isolate collection was a significant predictor of
      concordance of methicillin resistance in swabs and isolates (odds ratio 6.6, 95%
      CI 1.6-28.2). INTERPRETATION: A positive result from MRSA screening predicted
      methicillin resistance in a culture-positive clinical infection with S. aureus.
      Negative results on MRSA screening were most useful for excluding methicillin
      resistance of a subsequent infection with S. aureus when the screening swab was
      obtained within 48 hours before collection of the clinical isolate.

PMID- 24016795
TI  - Urinary obstruction from sexual practice involving magnetized beads inserted in
      the male urethra.

PMID- 24016797
TI  - Candidaemia in the non-neutropenic patient: a critique of the guidelines.
AB  - Several guidelines have been published on the management of candidaemia. These
      guidelines vary in their recommendations, and the lack of consistency between the
      guidelines has implications for the management of candidaemia. We critiqued five
      guidelines, including the Infectious Diseases Society of America (IDSA)
      Guidelines for the Management of Candidiasis, the Canadian Clinical Practice
      Guidelines for Invasive Candidiasis in Adults, the Joint Recommendations of the
      German Speaking Mycological Society and the Paul-Ehrlich-Society for
      Chemotherapy, the European Society of Clinical Microbiology and Infectious
      Diseases (ESCMID) Guideline for the Diagnosis and Management of Candida Diseases,
      and the Brazilian Guidelines for the Management of Candidiasis. The
      recommendations in these guidelines vary in all major areas of management,
      including choice of initial therapy, species-specific therapy (Candida glabrata
      and Candida parapsilosis), transition to oral therapy (3 days as per IDSA but 10
      days as per ESCMID), catheter removal and specialty referrals. We found that too
      much emphasis has been placed on themes such as predicting the infecting species
      (and therefore fluconazole susceptibility) or the need for investigations such as
      echocardiography. We also stress that guidelines fail to provide adequate
      information (due to lack of evidence) on the most relevant issues that clinicians
      face when managing candidaemia, such as the place for fluconazole in the
      treatment of C. glabrata, the clinical relevance of dose-dependent susceptibility
      to fluconazole, and the timing of step-down therapy. 

PMID- 24016798
TI  - Synthetic organic compounds with potential for bacterial biofilm inhibition, a
      path for the identification of compounds interfering with quorum sensing.
AB  - New unconventional approaches to the development of antimicrobial drugs must
      target inhibition of infection stages leading to host colonisation or virulence
      itself, rather than bacterial viability. Amongst the most promising
      unconventional targets for the development of new antimicrobial drugs is
      bacterial adherence and biofilm formation as well as their control system, the
      quorum-sensing (QS) system, a mechanism of communication used to co-ordinate
      bacterial activities. Here we describe the evaluation of synthetic organic
      compounds as bacterial biofilm inhibitors against a panel of clinically relevant
      Gram-positive and Gram-negative bacterial strains. This approach has successfully
      allowed the identification of five compounds (GEt, GHex, GOctad, G19 and C33)
      active not only against bacterial biofilms but also displaying potential to be
      used as antagonists and/or inhibitors of bacterial QS. 

PMID- 24016800
TI  - Chemical bonding-induced low dielectric loss and low conductivity in high-K
      poly(vinylidenefluoride-trifluorethylene)/graphene nanosheets nanocomposites.
AB  - Blending high-permittivity (epsilonr) ceramic powders or conductive fillers into
      polymers to form 0-3-type composites has been regarded as one of the most
      promising processes to achieve high-dielectric-permittivity materials with
      excellent processing performance. The high dielectric loss and conductivity
      induced by the interface between the matrix and fillers as well as the leakage
      current have long been a great challenge of dielectric composites, and the
      resolution of these challenges is still an open question. In this work,
      poly(vinylidenefluoride-trifluorethylene with double bonds)/graphene nanosheets
      (P(VDF-TrFE-DB)/GNS) terpolymer nanocomposites were fabricated via a solution
      cast process. GNSs were functionalized with KH550 to improve the dispersion in
      the terpolymer matrix solution and crosslinked with P(VDF-TrFE-DB) by a free
      radical addition reaction in the nanocomposites. Compared with neat terpolymer,
      significantly increased dielectric permittivity and a low loss were observed for
      the composites. For instance, at 1 kHz the P(VDF-TrFE-DB)/GNS composites with 4
      vol % GNS possessed a dielectric permittivity of 74, which is over seven times
      larger than that of neat terpolymer. However, a rather low dielectric loss (0.08
      at 1 kHz) and conductivity (3.47 * 10(-7) S/m at 1 kHz) are observed in the P(VDF
      TrFE-DB)/GNS composites containing up to 12 vol % GNS. The covalent bonding
      constructed between P(VDF-TrFE-DB) and GNS is responsible for the reduced aspect
      ratio of the GNS and the crystalline properties of P(VDF-TrFE-DB) as well as the
      improved compatibility between them. As a result, the high-dielectric-loss
      conductivity of polymer composites, mainly induced by conduction loss and the
      interface polarization between the matrix and filler, were effectively
      restricted. Meanwhile, the 3D network established between P(VDF-TrFE-DB) and GNS
      endows the P(VDF-TrFE-DB)/GNS composites at high temperature with excellent
      mechanical and dielectric properties. Besides preparing high-performance
      dielectric composites, this facile route may also be utilized to fabricate high
      performance nanocomposites by inhibiting the poor compatibility between fillers
      and polymeric matrix. 

PMID- 24016799
TI  - Pharmacokinetics and efficacy of liposomal polymyxin B in a murine pneumonia
      model.
AB  - Polymyxin B (PB) is increasingly used as the last treatment for multidrug
      resistant (MDR) Gram-negative bacterial infections. In this study, serum and
      epithelial lining fluid (ELF) pharmacokinetics and the efficacy of a PB liposomal
      formulation were investigated. Two groups of 24 Swiss Webster mice were
      intravenously administered PB liposomes or PB aqueous solution at ca. 3 mg/kg.
      Serum and ELF samples were collected for up to 6 h to quantify major PB
      components. Three groups of neutropenic mice (n = 6/group) were infected with a
      clinical MDR Pseudomonas aeruginosa strain followed by intravenous administration
      of PB liposomes or PB aqueous solution at 3 mg/kg every 6 h or sham (drug-free)
      liposomes every 6 h. Bacterial burden in animal lung tissues was quantified after
      24 h of therapy and was compared using one-way ANOVA. Survival of infected
      animals over time (n = 10/group) was evaluated by Kaplan-Meier analysis and log
      rank test. In the pharmacokinetic study, the AUC ratio in ELF between liposome
      and aqueous solution groups ranged from 4.6 to 11.1 for various major PB
      components. In the efficacy study, for strain PA 9019 a significantly lower
      bacterial burden was seen in the liposomal group (3.8 +/- 0.7 vs. 7.9 +/- 0.8
      log(10)CFU/g in the aqueous solution group), which subsequently prolonged
      survival of infected animals. In this study, treatment with a PB liposomal
      formulation yielded higher drug penetration into pulmonary ELF, which resulted in
      superior efficacy. However, further investigations on the clinical utility of the
      PB liposomal formulation are warranted.

PMID- 24016801
TI  - Persistent valve of systemic venous sinus: a cause of neonatal cyanosis.
AB  - Incomplete involution of valve of systemic venous sinus can present across a
      spectrum of anatomical lesions ranging from eustachian valve to division of right
      atrium (cor triatriatum dexter) with overlapping features. We present the case of
      a neonate presenting with cyanosis, having persistent valve of systemic venous
      sinus with anatomical details of the redundant tissue in right atrium suggesting
      an intermediate form between Chiari network and division of right atrium. 

PMID- 24016802
TI  - Medicinal uses, phytochemistry and pharmacology of Pongamia pinnata (L.) Pierre:
      a review.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pongamia pinnata (L.) Pierre is one of the many
      plants with diverse medicinal properties where all its parts have been used as
      traditional medicine in the treatment and prevention of several kinds of ailments
      in many countries such as for treatment of piles, skin diseases, and wounds. AIM
      OF THIS REVIEW: This review discusses the current knowledge of traditional uses,
      phytochemistry, biological activities, and toxicity of this species in order to
      reveal its therapeutic and gaps requiring future research opportunities. MATERIAL
      AND METHODS: This review is based on literature study on scientific journals and
      books from library and electronic sources such as ScienceDirect, PubMed, ACS,
      etc. RESULTS: Several different classes of flavonoid derivatives, such as
      flavones, flavans, and chalcones, and several types of compounds including
      terpenes, steroid, and fatty acids have been isolated from all parts of this
      plant. The pharmacological studies revealed that various types of preparations,
      extracts, and single compounds of this species exhibited a broad spectrum of
      biological activities such as antioxidant, antimicrobial, anti-inflammatory, and
      anti-diabetic activities. CONCLUSION: The results of several toxicity studies
      indicated that extracts and single compounds isolated from this species did not
      show any significant toxicity and did not cause abnormality on some rats' organs.
      Thus, this plant has a potential to be used as an effective therapeutic remedy
      due to its low toxicity towards mammalian cells. However, further study on
      chemical constituents and their mechanisms in exhibiting certain biological
      activities are needed to understand the full phytochemical profile and the
      complex pharmacological effects of this plant. In addition, further study on the
      toxicity of the other compounds isolated from this plant required to be assessed
      to ensure their eligibility to be used as sources of drugs.

PMID- 24016803
TI  - Colonisation endpoints in Streptococcus pneumoniae vaccine trials.
AB  - Evaluating vaccine efficacy for protection against colonisation (VEcol) with
      bacterial pathogens is an area of growing interest. In this article, we consider
      estimation of VEcol for colonisation with Streptococcus pneumoniae (the
      pneumococcus). Colonisation is a common, recurrent and multi-type endpoint that
      requires both careful definition of the vaccine efficacy parameter and the
      corresponding method of estimation. We review recent developments in the area and
      provide practical guidelines for choosing the estimand and the estimation method
      in trials with a colonisation endpoint. We concentrate on methods that are based
      on a cross-sectional study design, in which only one nasopharyngeal sample is
      obtained per study subject. 

PMID- 24016804
TI  - Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: exposure
      prevalence, preterm delivery, and specific birth defects.
AB  - We estimated exposure prevalence and studied potential risks for preterm delivery
      (PTD) and specific birth defects associated with exposure to the unadjuvanted
      pH1N1-containing vaccines in the 2009-2010 and 2010-2011 influenza seasons. We
      used data from 4 regional centers in the United States collected as part of the
      Slone Epidemiology Center's Birth Defects Study. For PTD, propensity score
      adjusted time-varying hazard ratios (HRs) and 95% confidence intervals (CIs) were
      estimated for exposure anytime in pregnancy and for each trimester. For 41
      specific major birth defects, propensity score-adjusted odds ratios (ORs) and 95%
      confidence intervals (CIs) were estimated. Among 4191 subjects, there were 3104
      mothers of malformed (cases) and 1087 mothers of nonmalformed (controls).
      Exposure prevalences among controls were 47% for the 2009-2010 season and 38% for
      the 2010-2011 season; prevalence varied by geographic region. Results for PTD
      differed between the two seasons, with risks above and below the null for the
      2009-2010 and 2010-2011 seasons, respectively. For 41 specific birth defects,
      most adjusted ORs were close to 1.0. Three defects had adjusted ORs>2.0 and four
      had risks<0.5; however, 95% CIs for these were wide. CONCLUSIONS: Among women
      exposed to pH1N1 vaccine, we found a decreased risk for PTD in the 2010-2011
      season; risk was increased in 2009-2010, particularly following exposure in the
      first trimester, though the decrease in gestational length was less than 2 days.
      For specific major defects, we found no meaningful evidence of increased risk for
      specific congenital malformations following pH1N1 influenza vaccinations in the
      2009-2010 and 2010-2011 seasons.

PMID- 24016805
TI  - Detection of Clostridium sordellii strains expressing hemorrhagic toxin (TcsH)
      and implications for diagnostics and regulation of veterinary vaccines.
AB  - Clostridium sordellii is a Gram positive anaerobic bacterium that causes multiple
      disease syndromes in both humans and animals. As with many clostridial pathogens,
      toxins contribute to the virulence of C. sordellii. Two large toxins have been
      identified: a lethal toxin (TcsL) and a hemorrhagic toxin (TcsH) which are
      similar in structure and function to Clostridium difficile toxin B (TcdB) and
      toxin A (TcdA), respectively. While TcdA, TcdB, and TcsL have been extensively
      studied, relatively little is known about TcsH. This study elucidated the TcsH
      gene sequence using whole genome sequencing, compared the genotype with toxin
      expression of 52 C. sordellii strains, and examined the role of TcsH in batch
      release potency tests required for veterinary vaccines licensed in the United
      States and other testing utilizing WHO standard antitoxin. Data from this study
      will assist in future research to clarify the TcsH contribution to the
      pathogenesis of C. sordellii infections and may aid in the development of
      improved vaccines. 

PMID- 24016807
TI  - Hepatitis B and influenza vaccines: important occupational vaccines differently
      perceived among medical students.
AB  - Healthcare personnel (HCP) are at risk from occupational exposure to airborne and
      bloodborne pathogens, and the risk of infection among HCP is greater than among
      the general population. The aim of the study was to characterize attitudes toward
      occupational recommended vaccines as well as the perception of risks of
      occupationally acquired infections. We surveyed 650 medical students to assess
      their perception of influenza and hepatitis B and their opinions and beliefs
      about influenza and hepatitis B vaccines. We found differences between pre
      clinical and clinical students regarding the uptake of influenza and hepatitis B
      vaccines, about the chances of being occupationally infected with influenza or
      hepatitis B, and about the likelihood of suffering from severe side-effects
      following immunization. Interestingly, the risk perception varied drastically
      between the two vaccine-preventable diseases hepatitis B and influenza. Medical
      students rated the probability of contracting hepatitis B due to a work-related
      exposure and the severity of disease significantly higher than for influenza, and
      this may be an explanation for the greater acceptance of the hepatitis B vaccine.
      Furthermore, our findings suggest that medical students are frequently inaccurate
      in assessing their own risk level, and their specific knowledge about both
      diseases and the severity of these diseases proved to be unsatisfactory. 

PMID- 24016808
TI  - Cross-clade protection against H5N1 HPAI strains recently isolated from
      commercial poultry in Egypt with a single dose of a baculovirus based vaccine.
AB  - The current avian influenza epidemic in Egypt caused by circulation of
      genetically and antigenically diverse H5N1 HPAI viruses in poultry is controlled
      by applying vaccination among other measures. In this context, the use of a DIVA
      (differentiating infected from vaccinated animals) vaccination strategy utilizing
      a vaccine capable of inducing protection against multiple antigenic variants may
      result as an additional control tool to the existing ones. In this study the
      efficacy of a single-shot recombinant baculovirus-based vaccine in specific
      pathogen-free chickens was tested by experimental challenge with genetically and
      antigenically diverse H5N1 HPAI viruses belonging to clades 2.2.1 and 2.2.1.1,
      which have been circulating in Egypt since 2010. A single dose of vaccine,
      administration at 10 days of age, was shown to confer 100% clinical protection,
      with a decrease or suppression of virus shedding. 

PMID- 24016806
TI  - Vaccines against gonorrhea: current status and future challenges.
AB  - Gonorrhea occurs at high incidence throughout the world and significantly impacts
      reproductive health and the spread of human immunodeficiency virus. Current
      control measures are inadequate and seriously threatened by the rapid emergence
      of antibiotic resistance. Progress on gonorrhea vaccines has been slow; however,
      recent advances justify significant effort in this area. Conserved vaccine
      antigens have been identified that elicit bactericidal antibodies and, or play
      key roles in pathogenesis that could be targeted by a vaccine-induced response. A
      murine genital tract infection model is available for systematic testing of
      antigens, immunization routes and adjuvants, and transgenic mice exist to relieve
      some host restrictions. Furthermore, mechanisms by which Neisseria gonorrhoeae
      avoids inducing a protective adaptive response are being elucidated using human
      cells and the mouse model. Induction of a Th1 response in mice clears infection
      and induces a memory response, which suggests Th1-inducing adjuvants may be key
      in vaccine-induced protection. Continued research in this area should include
      human testing and clinical studies to confirm or negate findings from
      experimental systems and to define protective host factors. 

PMID- 24016809
TI  - Risks and safety of pandemic H1N1 influenza vaccine in pregnancy: birth defects,
      spontaneous abortion, preterm delivery, and small for gestational age infants.
AB  - INTRODUCTION: There is a need for additional information on the fetal risks and
      relative safety of the pandemic H1N1 monovalent or trivalent influenza (pH1N1)
      containing vaccines in women exposed during pregnancy. METHODS: To assess risks
      and relative safety of the pH1N1-containing vaccines, we conducted a prospective
      cohort study of pH1N1-vaccine-exposed and unexposed comparison women residing in
      the U.S. or Canada who were recruited during pregnancy and followed to outcome
      between October 2009 and August 2012. For exposure to the pH1N1 vaccine, adjusted
      relative risks (RRs) and 95% confidence intervals (CIs) were estimated for major
      birth defects and infants small for gestational age. Adjusted hazard ratios (HRs)
      and 95% CIs were estimated for spontaneous abortion and preterm delivery for time
      varying exposure. RESULTS: There were 1032 subjects available for analysis; 841
      women were exposed to a pH1N1-containing vaccine in pregnancy, and 191 women were
      unexposed to any influenza vaccine in pregnancy. Nine of 328 (2.7%) first
      trimester-exposed pregnancies resulted in an infant with a major birth defect
      compared to 6/188 (3.2%) in the unexposed (adjusted RR 0.79, 95% CI 0.26-2.42).
      The HR for spontaneous abortion was not elevated (adjusted HR 0.92, 95% CI 0.31
      2.72). Adjusted HRs for preterm delivery were elevated for exposure anytime in
      pregnancy (3.28, 95% CI 1.25-8.63), specifically with exposure in the 1st or 2nd
      trimester. However, the mean decrease in gestational age in the exposed
      pregnancies was approximately three days. Adjusted RRs for small for gestational
      age infants on weight and length approximated 1.0. CONCLUSIONS: For the 2009-12
      influenza seasons combined, we found no meaningful evidence of increased RR or HR
      for major birth defects, spontaneous abortion, or small for gestational age
      infants. There was some evidence of an increased HR for preterm delivery
      following pH1N1-influenza vaccine exposure; however the decrease in gestational
      age on average was approximately three days.

PMID- 24016810
TI  - Safety and immunogenicity of a quadrivalent inactivated influenza vaccine in
      adults.
AB  - BACKGROUND AND AIMS: Although two antigenically distinct B strain lineages of
      influenza have co-circulated globally since the mid-1980s, trivalent influenza
      vaccines (TIVs) contain only one, resulting in frequent mismatches. This study
      examined the safety and immunogenicity of an inactivated quadrivalent influenza
      vaccine (QIV) candidate. METHODS: This was a phase III, randomized, active
      controlled, multicenter trial in adults during the 2011/2012 influenza season.
      Enrollment was stratified to include equal numbers of subjects 18-60 and >60
      years of age. Subjects were randomized 5:1:1 to be vaccinated with the QIV, the
      licensed TIV, or an investigational TIV containing the alternate B strain
      lineage. Hemagglutinin inhibition antibody titers were assessed pre-vaccination
      and 21 days post-vaccination. RESULTS: 1116 subjects were vaccinated with QIV,
      226 with the licensed TIV, and 223 with the investigational TIV. For all four
      vaccine strains, antibody responses to the QIV were non-inferior to the response
      to the TIV for the matched strains. For both B strains, post-vaccination antibody
      responses to the QIV were superior to the responses to the TIVs lacking the
      corresponding B strain. The QIV met all European Medicines Agency criteria for
      all four vaccine strains. Solicited reactions, unsolicited adverse events, and
      serious adverse events were similar for the QIV and pooled TIV groups. The most
      commonly reported solicited reactions were injection-site pain, headache, and
      myalgia, and most solicited reactions were mild or moderate and appeared and
      resolved within 3 days of vaccination. No treatment-related serious adverse
      events or deaths were reported. CONCLUSIONS: The inactivated QIV was well
      tolerated without any safety concerns. For all four vaccine strains, antibody
      responses to the QIV were superior to the responses to TIV for the unmatched
      strains and non-inferior for the matched strains. QIV could therefore help
      address an unmet need due to mismatched B strains in previous influenza vaccines.
      CLINICAL TRIAL REGISTRY NUMBER: EudraCT: 2011-001976-21.

PMID- 24016812
TI  - Is it necessary to adjust for calendar time in a test negative design?:
      Responding to: Jackson ML, Nelson JC. The test negative design for estimating
      influenza vaccine effectiveness. Vaccine 2013;31(April (17)):2165-8.

PMID- 24016813
TI  - Preparation and immunoprotection of subgroup B avian leukosis virus inactivated
      vaccine.
AB  - OBJECTIVES: To develop an inactivated vaccine against subgroup B avian leukosis
      virus (ALV-B) and determine if vaccination of chicken breeders could protect
      young chicks from ALV-B horizontal infection at early stage and accelerate
      eradication progress. METHODS: Chicken embryo fibroblast (CEF) cells were
      inoculated with SDAU09C2 strain of ALV-B and ALV-CEF was inactivated for
      preparation of oil-adjuvant vaccine. Eggs were collected from un-vaccinated and 9
      vaccinated great parent female chickens for incubation. 1-day-old chicks were
      bled for testing their maternal antibodies to ALV-A/B and then inoculated with
      ALV-B. Viremia and cloaca p27 detection dynamics were tested and compared between
      chick groups with or without maternal antibody to ALV. RESULTS: In 3 weeks after
      3 vaccination with the inactivated vaccine, all 9 vaccinated breeders developed
      high antibody titers against ALV-A/B with ELISA read values of 1.69-1.89 (the
      positive base line was 0.4) and kept at the high titers for at least another 4
      weeks. Maternal antibody was detected in 70% (12/17) of chicks from breeders with
      high antibody titers to ALV-A/B. Only 4 of 12 chickens with maternal antibodies
      developed temporary viremia and no viremia was detected in the left 8 maternal
      antibody positive chickens during the whole 14 week after inoculation of ALV-B at
      1 day of age. But the persistent viremia was detected in 2-8 weeks in all 9
      maternal antibody negative chickens and the viremia persisted in the whole tested
      period of 14 weeks after inoculation of ALV-B. CONCLUSIONS: The inactivated ALV-B
      vaccine could induce high titer antibody reaction to ALV-B, it could provide
      maternal antibodies to 1-day-old chickens and protect chickens from early
      infection of ALV-B.

PMID- 24016815
TI  - Therapy: conquering a brave new world.

PMID- 24016811
TI  - Current status and prospects for development of an HSV vaccine.
AB  - Herpes simplex virus type 2 (HSV-2) infects 530million people, is the leading
      cause of genital ulcer disease, and increases the risk of HIV-1 acquisition.
      Although several candidate vaccines have been promising in animal models,
      prophylactic and therapeutic vaccines have not been effective in clinical trials
      thus far. Null results from the most recent prophylactic glycoprotein D2 subunit
      vaccine trial suggest that we must reevaluate our approach to HSV-2 vaccine
      development. We discuss HSV-2 pathogenesis, immunity, and vaccine efforts to
      date, as well as the current pipeline of candidate vaccines and design of trials
      to evaluate new vaccine constructs. 

PMID- 24016816
TI  - Competencies for yoga therapists: what we need to know and master.

PMID- 24016814
TI  - Prevalence and predictors of maternal seasonal influenza vaccination in Hong
      Kong.
AB  - BACKGROUND: Pregnant women infected with influenza virus are more likely to
      experience severe complications when compared with their non-pregnant peers. Yet
      influenza vaccine uptake is low among pregnant women. The purpose of this study
      was to assess the prevalence of seasonal influenza vaccine uptake among pregnant
      women in Hong Kong and to identify predictors of vaccine uptake. METHODS: Using a
      multi-center cross-sectional design, we recruited 2822 new mothers during their
      immediate postpartum stay from all eight public obstetric hospitals in Hong Kong.
      We assessed antenatal maternal influenza vaccination status as well as health
      beliefs and perceptions toward influenza and influenza vaccination. Bivariable
      and multivariable logistic regression was used to identify the predictors of
      vaccination uptake. RESULTS: Only 49 (1.7%; 95% CI 1.3-2.3%) participants were
      vaccinated during their pregnancy. Fear that the vaccine would cause harm to the
      fetus or themselves were the most common reasons for not being vaccinated. Being
      aware of the vaccination recommendations (OR=2.69; 95% CI 1.06-6.82), being
      advised by a health-care provider (OR=6.30; 95% CI 3.19-12.46), history of
      vaccination (OR=2.47; 95% CI 1.25-4.91), perceived susceptibility to influenza
      infection (OR=3.67; 95% CI 1.64-8.22), and perceived benefits of influenza
      vaccination (OR=9.98; 95% CI 3.79-26.24) were all independently associated with
      vaccination. Perceived barriers to vaccination (OR=0.17; 95% CI 0.07-0.40) were
      strongly associated with failure to vaccinate. CONCLUSIONS: Low seasonal
      influenza vaccination uptake among Hong Kong pregnant women was related to a
      number of factors, all of which are amenable to interventions. Vaccination
      promotion strategies need to focus on encouraging health-care providers to
      discuss vaccination with their pregnant clients and in providing pregnant women
      with accurate and unbiased information about the risks of influenza infection and
      the benefits of vaccination.

PMID- 24016817
TI  - The value of assessment in yoga therapy programs.

PMID- 24016818
TI  - Innovations in yoga therapist education: developing a yoga therapy program in an
      academic setting.

PMID- 24016819
TI  - Defining yoga-nidra: traditional accounts, physiological research, and future
      directions.
AB  - The term yoga-nidra has been used in many empirical studies to refer to
      relaxation and guided imagery. These techniques do not represent the intention or
      physiological correlates of yoganidra discussed in the traditional yoga
      literature. We propose an operational definition of yoga-nidra that is supported
      by several physiologically testable hypotheses regarding its outcomes and
      effects. Traditional descriptions of yoga-nidra and contemporary accounts of its
      practice are reviewed, and studies examining the physiological correlates of yoga
      nidra are examined. Proposed hypotheses for future research using this
      operational definition are provided. 

PMID- 24016820
TI  - Yoga, vertebral fractures, and osteoporosis: research and recommendations.
AB  - BACKGROUND: Osteoporosis is characterized by decreased bone density that leaves
      bones fragile and highly susceptible to fracture. Globally, 1 in 3 women and 1 in
      5 men older than 50 will suffer from an osteoporotic fracture, and those
      individuals will experience a considerably higher risk of postfracture mortality
      than will the general population. Gentle, weight-bearing exercises such as yoga
      can help prevent or cease the progression of osteoporosis; however, there is
      insufficient data regarding which yoga poses present the least risk and are most
      beneficial to individuals with reduced bone density. OBJECTIVES: Review the
      extant literature about the risks and benefits to the spine of particular forms
      of movement and consider recommendations relative to the practice of yoga.
      METHODS: A review of the PubMed, Medline, and Cochrane databases was conducted
      that identified manuscripts published between 1966 and 2011 about topics related
      to osteoporosis and spinal movement. CONCLUSIONS: Movements involving spinal
      flexion can increase risk for vertebral compression fractures; however, a
      combination of mild spinal flexion and extension may prove beneficial. Moderate,
      weight-bearing activities that strengthen the muscles supporting the spinal
      column, promote balance, improve posture, and enhance quality of life appear to
      be of greatest benefit. Ample evidence supports the importance of varied spinal
      movement for preserving the health and strength of the vertebral bodies. Exercise
      modifications suitable for high-risk individuals may be counterproductive for
      those at low risk for vertebral fractures. Yoga therapists are cautioned to not
      apply a one-size-fits-all approach when working with this population. Well
      designed empirical studies are needed to further our understanding of which yoga
      poses present the least risk and are of greatest benefit to individuals with
      osteoporosis.

PMID- 24016821
TI  - Evaluation of the benefits of a kripalu yoga program for police academy trainees:
      a pilot study.
AB  - BACKGROUND: Law enforcement ranks as one of the most stressful occupations in the
      world. Yoga is a mind-body practice composed of postures, breathing, and
      meditation techniques, and is known for its beneficial effects on stress and mood
      disturbance. OBJECTIVES: This pilot study evaluated the effects of Kripalu yoga
      on perceived stress, mood, and mindfulness during police academy training.
      METHOD: Forty-two recruits participated in a 6-class yoga intervention.
      Participants completed the Profile of Mood States-Short Form, Perceived Stress
      Scale, and the Five Facet Mindfulness Questionnaire prior to and immediately
      following completion of the yoga program, as well as an exit survey. RESULTS:
      Paired samples t-tests revealed significant postintervention changes in perceived
      stress and mood, reductions in tension and fatigue, and a trend toward reduced
      anger. Changes in mindfulness were not detected. The exit survey indicated
      perceived benefits of yoga for some participants. CONCLUSIONS: This preliminary
      study suggests that yoga may be beneficial for reducing stress, tension, and
      fatigue among police academy trainees. Future longitudinal randomized controlled
      trials are needed to evaluate its full potential as a permanent component of
      police academy training.

PMID- 24016823
TI  - Production of reactive oxygen species by withaferin A causes loss of type
      collagen expression and COX-2 expression through the PI3K/Akt, p38, and JNK
      pathways in rabbit articular chondrocytes.
AB  - Withaferin A (WFA) is a major chemical constituent of Withania somnifera, also
      known as Indian ginseng. Many recent reports have provided evidence of its anti
      tumor, anti-inflammation, anti-oxidant, and immune modulatory activities.
      Although the compound appears to have a large number of effects, its defined
      mechanisms of action have not yet been determined. We investigated the effects of
      WFA on loss of type collagen expression and inflammation in rabbit articular
      chondrocytes. WFA increased the production of reactive oxygen species, suggesting
      the induction of oxidative stress, in a dose-dependent manner. Also, we confirmed
      that WFA causes loss of type collagen expression and inflammation as determined
      by a decrease of type II collagen expression and an increase of cyclooxygenase-2
      (COX-2) expression via western blot analysis in a dose- and time- dependent
      manner. WFA also reduced the synthesis of sulfated proteoglycan via Alcian blue
      staining and caused the synthesis of prostaglandin E2 (PGE2) via assay kit in
      dose- and time-dependent manners. Treatment with N-acetyl-L-cysteine (NAC), an
      antioxidant, inhibited WFA-induced loss of type II collagen expression and
      increase in COX-2 expression, accompanied by inhibition of reactive oxygen
      species production. WFA increased phosphorylation of both Akt and p38. Inhibition
      of PI3K/Akt, p38, and JNK with LY294002 (LY), SB203580 (SB), or SP600125 (SP) in
      WFA-treated cells rescued the expression of type II collagen and suppressed the
      expression of COX-2. These results demonstrate that WFA induces loss of type
      collagen expression and inflammation via PI3K/Akt, p38, and JNK by generating
      reactive oxygen species in rabbit articular chondrocytes.

PMID- 24016824
TI  - Apparent diffusion coefficient for discriminating metastatic from non-metastatic
      lymph nodes in primary rectal cancer.
AB  - OBJECTIVE: To investigate whether the apparent diffusion coefficient (ADC) could
      be used to discriminate metastatic from non-metastatic lymph nodes (LNs) in
      patients with primary rectal cancer. METHODS: This study investigated 34 patients
      (male: 12, female: 22, mean: 62.7, range: 37-82) who underwent 1.5-T MRI with
      diffusion-weighted imaging (DWI) and subsequent surgical resection. A blinded
      radiologist measured the ADC value in each regional LN after referring to the T2
      weighted images and DWI. The t-test was used to compare the mean ADC values of
      the metastatic and non-metastatic LNs. A ROC analysis was performed to calculate
      the diagnostic performance and obtain the optimal cut-off. The histopathological
      results were used as the reference standard. RESULTS: 114 LNs (46 metastatic and
      68 non-metastatic) were matched and analyzed. The mean ADC of the metastatic LNs
      was significantly lower than that of the non-metastatic LNs (0.9 +/- 0.15 * 10(
      3) mm(2)/s; 1.1 +/- 0.22 * 10(-3) mm(2)/s, P<0.0001). The area under the ROC
      curve was 0.734 (95% confidence interval, 0.644-0.812). When an ADC value of 1.0
      * 10(-3) mm(2)/s was used as the cut-off, a maximum accuracy of 72% was
      calculated (sensitivity, 78%; specificity, 67%). CONCLUSIONS: Although ADC could
      be used to discriminate metastatic from non-metastatic LNs, the diagnostic
      accuracy is approximately 70%.

PMID- 24016822
TI  - 2013 SYR Accepted Poster Abstracts.

PMID- 24016825
TI  - Correlation between MRI and double-balloon urethrography findings in the
      diagnosis of female periurethral lesions.
AB  - This study aims to evaluate the correlation of MRI findings with double-balloon
      urethrography (DBU) in diagnosing female urethral diverticula and other
      periurethral lesions. In this retrospective study, females with clinically
      suspected periurethral lesions who underwent both MRI and DBU between 2008 and
      2012 were evaluated. MRI was performed on a 1.5 Tesla unit using a pelvic phased
      array coil. Protocol included small FOV pelvic images, multiplanar T2-w, T1-w
      with and without contrast injection. DBU was performed by a dedicated catheter.
      Images were evaluated in consensus by two readers. Diverticula were evaluated by,
      size, number, complexity, location and connection to urethra, and other
      periurethral lesions were evaluated by size, location and connection. Supplement
      clinical and surgical data were retrieved from medical records and telephone
      interviews. Seventeen females (mean age 44 years, range 20-69) were included in
      the study. Diverticula were diagnosed by both modalities (9 cases), by neither (6
      cases, 88% correlation) by MRI alone (1 case) and by DBU alone (1 case). Among
      diverticula, correlation of number, complexity, location and demonstration of
      connection to urethra was 89%, 67%, 67%, and 56%, respectively. Alternative
      diagnosis solely by MRI included vaginal wall cysts (3 cases), endometriosis (1
      case) and ectopic ureter (1 case). No periurethral lesion was found by either
      modality in 2 cases. The correlation between MRI and DBU in diagnosing female
      periurethral lesions is very good for anatomical delineation of diverticula. MRI,
      which does not involve radiation, may also indicate alternative diagnoses that
      can contribute to proper patient management.

PMID- 24016826
TI  - Good correlation does not automatically imply good agreement: the trouble with
      comparing tumour size by breast MRI versus histopathology.

PMID- 24016827
TI  - Incomplete pulmonary fissures evaluated by volumetric thin-section CT: semi
      quantitative evaluation for small fissure gaps identification, description of
      prevalence and severity of fissural defects.
AB  - OBJECTIVE: To assess the interobserver agreement for a semi-quantitative
      evaluation of the interlobar fissures integrity in volumetric thin-section CT
      images, looking for more detailed information regarding fissural defects; and
      describe prevalence and severity of fissural defects between the different
      functional groups of subjects. MATERIALS AND METHODS: Volumetric scans of 247
      individuals exposed to tobacco with different functional status (normal to severe
      COPD), were retrospectively and independently evaluated by 2 chest radiologists,
      with a consensual reading additionally with a third reader in disagreement cases.
      Right oblique (RO), right horizontal (RH) and left oblique fissures (LO)
      integrity was estimated using a 5% scale. GOLD classification was available for
      all subjects. RESULTS: Interobserver agreement (weighted Kappa-index) for
      fissural categorization was 0.76, 0.70 and 0.75, for RO, RH and LO, respectively.
      Final evaluation found 81%, 89% and 50% of RO, RH and LO to be incomplete, with
      respective mean integrity of 80%, 58% and 80%. Small fissure gaps (<10%) were
      present in 30% of patients. Prevalence and severity of fissural defects were not
      different between the GOLD categories. CONCLUSIONS: A substantial agreement
      between readers was found in the analysis of interlobar fissures integrity. The
      semi-quantitative method allowed a detailed description of the fissural defects,
      information that can be important, for example, in endoscopic lung volume
      reduction therapies for emphysema. Small fissure gaps, overlooked in previous
      studies, were found in almost a third of the patients. A higher than previously
      described prevalence of fissural defects was described, but without significant
      differences among the distinct functional groups.

PMID- 24016828
TI  - Radiology related applications: potential benefits and hazards.

PMID- 24016829
TI  - Validation of Fourier decomposition MRI with dynamic contrast-enhanced MRI using
      visual and automated scoring of pulmonary perfusion in young cystic fibrosis
      patients.
AB  - PURPOSE: To validate Fourier decomposition (FD) magnetic resonance (MR) imaging
      in cystic fibrosis (CF) patients with dynamic contrast-enhanced (DCE) MR imaging.
      MATERIALS AND METHODS: Thirty-four CF patients (median age 4.08 years; range 0.16
      30) were examined on a 1.5-T MR imager. For FD MR imaging, sets of lung images
      were acquired using an untriggered two-dimensional balanced steady-state free
      precession sequence. Perfusion-weighted images were obtained after correction of
      the breathing displacement and Fourier analysis of the cardiac frequency from the
      time-resolved data sets. DCE data sets were acquired with a three-dimensional
      gradient echo sequence. The FD and DCE images were visually assessed for
      perfusion defects by two readers independently (R1, R2) using a field based
      scoring system (0-12). Software was used for perfusion impairment evaluation (R3)
      of segmented lung images using an automated threshold. Both imaging and
      evaluation methods were compared for agreement and tested for concordance between
      FD and DCE imaging. RESULTS: Good or acceptable intra-reader agreement was found
      between FD and DCE for visual and automated scoring: R1 upper and lower limits of
      agreement (ULA, LLA): 2.72, -2.5; R2: ULA, LLA: +/- 2.5; R3: ULA: 1.5, LLA: -2. A
      high concordance was found between visual and automated scoring (FD: 70-80%, DCE:
      73-84%). CONCLUSIONS: FD MR imaging provides equivalent diagnostic information to
      DCE MR imaging in CF patients. Automated assessment of regional perfusion defects
      using FD and DCE MR imaging is comparable to visual scoring but allows for
      percentage-based analysis.

PMID- 24016830
TI  - Response to 'Comment on: 3-T direct MR arthrography of the wrist: Value of finger
      trap distraction to assess intrinsic ligament and triangular fibrocartilage
      complex tears'.

PMID- 24016831
TI  - Comment on "3-T direct MR arthrography of the wrist: value of finger trap
      distraction to assess intrinsic ligament and triangular fibrocartilage complex
      tears", Cerny M et al. Eur J Radiol (2013).

PMID- 24016832
TI  - Radiation dose reduction in soft tissue neck CT using adaptive statistical
      iterative reconstruction (ASIR).
AB  - PURPOSE: To compare objective and subjective image quality in neck CT images
      acquired at different tube current-time products (275 mAs and 340 mAs) and
      reconstructed with filtered-back-projection (FBP) and adaptive statistical
      iterative reconstruction (ASIR). MATERIALS AND METHODS: HIPAA-compliant study
      with IRB approval and waiver of informed consent. 66 consecutive patients were
      randomly assigned to undergo contrast-enhanced neck CT at a standard tube-current
      time-product (340 mAs; n = 33) or reduced tube-current-time-product (275 mAs, n =
      33). Data sets were reconstructed with FBP and 2 levels (30%, 40%) of ASIR-FBP
      blending at 340 mAs and 275 mAs. Two neuroradiologists assessed subjective image
      quality in a blinded and randomized manner. Volume CT dose index (CTDIvol), dose
      length-product (DLP), effective dose, and objective image noise were recorded.
      Signal-to-noise ratio (SNR) was computed as mean attenuation in a region of
      interest in the sternocleidomastoid muscle divided by image noise. RESULTS:
      Compared with FBP, ASIR resulted in a reduction of image noise at both 340 mAs
      and 275 mAs. Reduction of tube current from 340 mAs to 275 mAs resulted in an
      increase in mean objective image noise (p=0.02) and a decrease in SNR (p = 0.03)
      when images were reconstructed with FBP. However, when the 275 mAs images were
      reconstructed using ASIR, the mean objective image noise and SNR were similar to
      those of the standard 340 mAs CT images reconstructed with FBP (p>0.05).
      Subjective image noise was ranked by both raters as either average or less-than
      average irrespective of the tube current and iterative reconstruction technique.
      CONCLUSION: Adapting ASIR into neck CT protocols reduced effective dose by 17%
      without compromising image quality.

PMID- 24016833
TI  - Achieving sustainable universal health coverage in low- and middle-income
      countries.

PMID- 24016834
TI  - Synthesis and evaluation of alpha-ketotriazoles and alpha,beta-diketotriazoles as
      inhibitors of Mycobacterium tuberculosis.
AB  - Two series of alpha-ketotriazole and alpha,beta-diketotriazole derivatives were
      synthesized and evaluated for antitubercular and cytotoxic activities. Among
      them, two alpha,beta-diketotriazole compounds, 6b and 9b, exhibited good
      activities (minimum inhibitory concentration = 7.6 MUM and 6.9 MUM, respectively)
      on Mycobacterium tuberculosis and multi-drug resistant M. tuberculosis strains
      and presented no cytotoxicity (IC50 > 50 MUM) on colorectal cancer HCT116 and
      normal fibroblast GM637H cell lines. These two compounds represent promising
      leads for further optimization.

PMID- 24016835
TI  - Circadian blood pressure pattern and right ventricular and right atrial
      mechanics: A two- and three-dimensional echocardiographic study.
AB  - The purpose of this investigation was to evaluate right ventricular (RV) and
      right atrial (RA) function and mechanics in untreated hypertensive patients with
      different blood pressure (BP) patterns by using two-dimensional (2DE) speckle
      tracking analyses and three-dimensional echocardiography (3DE). This cross
      sectional study included 174 recently diagnosed hypertensive patients. All
      patients underwent a 24-hour ambulatory BP monitoring and complete 2DE and 3DE
      examination, including 2DE speckle tracking analysis. Our results showed that 2DE
      RV global longitudinal strain was significantly lower in the non-dippers. Similar
      results were obtained for 2DE RV systolic and early diastolic strain rate. The RA
      longitudinal strain, as well as RA systolic and early diastolic strain rate, was
      decreased in non-dippers. Our results revealed that 3DE RV end-diastolic and end
      systolic volumes were increased, whereas 3DE RV ejection fraction was reduced in
      non-dipper hypertensive patients. Similar results were obtained for RA volumes
      and RA ejection fraction estimated by 2DE. Independent predictors of 3DE RV
      ejection fraction, 2DE RV and RA global longitudinal strain were left ventricular
      mass index and RV wall thickness. An additional independent predictor of the RV
      longitudinal strain was 3DE RV ejection fraction, and for RA longitudinal strain,
      an additional independent predictor was tricuspid E/e ratio. Two-DE speckle
      tracking evaluation and 3DE examination revealed that the RV and RA function and
      mechanics were more deteriorated in the non-dipper patients than in dipper
      untreated hypertensive patients.

PMID- 24016836
TI  - Response to the letter from Paul Drinka.

PMID- 24016837
TI  - Pavlovian contextual and instrumental biconditional discrimination learning in
      mice.
AB  - Genetically-modified animal models are a powerful tool for investigating the link
      between neurological and behavioral changes and for the development of
      therapeutic interventions. Executive function deficits are symptomatic of many
      human clinical disorders but few tasks exist for studying executive functions in
      mice. To address this need, we describe procedures for establishing Pavlovian
      contextual and instrumental biconditional discriminations (BCDs) in C57BL/6J
      mice. In the first experiment, contextual cues disambiguated when two short
      duration stimulus targets would be followed by food pellets. In the second
      experiment, discrete visual cues signaled when lever press or nose poke responses
      would be continuously reinforced with food pellets. Mice learned both BCDs as
      evidenced by differential responding in each cue during training and, more
      critically, during extinction testing. The implications of these findings for
      using BCD tasks to analyze the neural substrates of executive processing in
      animal models are discussed. 

PMID- 24016838
TI  - Individual differences in choice (in)flexibility but not impulsivity in the
      common marmoset: an automated, operant-behavior choice task.
AB  - Individual differences in behavioural flexibility are a significant issue in
      human psychopathology as well as in its animal models. We aimed to investigate
      individual variations of operant-choice behaviour in the common marmoset
      (Callithrix jacchus), a small New World primate, using a new operant panel with
      two hand-poking holes. METHODS: Experimental subjects (N=16) were presented with
      a choice between a Small & Soon (SS) vs a Large & Late (LL) food reward. After
      extensive training (31 daily sessions with no delay, during which a basal, large
      reward preference developed), the delay before release of LL was progressively
      increased (from 0 to 60 s, during 16 daily sessions; indifferent point at delay=9
      s). Subjects were classified as either "flexible" or "non-flexible",
      respectively, based on a decrease (or not) in the preference for LL with
      increasing delays. Each subject was also classified as "maximizer" (or "non
      maximizer") based on capacity (or not) to maximize the food payoff as delay
      increased. RESULTS: Upon delays shorter than the indifferent point (<9s), none of
      the subjects showed a shift from LL to SS, denoting a lack of delay-induced,
      cognitive impulsivity. Individual differences only emerged upon delays longer
      than the indifferent point (>9 s), when a preference shift could be interpreted
      as economically-driven. In general, a profile of few unrewarded hand-pokes in
      reaction to initial delays (i.e., a low motor impulsivity) and of clear-cut basal
      LL preference seemed to predict elevated flexibility of choices and better food
      payoff, which was typical of subjects classified as both "flexible & maximizer".
      CONCLUSION: These results provide normative data on the marmosets, which can be
      used as a model for the investigation of 1) individual differences in behavioural
      flexibility, as well as 2) biological mechanisms rooted in our evolutionary
      history.

PMID- 24016839
TI  - Angiotensin-(1-7) attenuates the anxiety and depression-like behaviors in
      transgenic rats with low brain angiotensinogen.
AB  - Transgenic rats with low brain angiotensinogen, TGR(ASrAOGEN)680, expressing an
      antisense RNA against angiotensinogen in glial cells, provide an interesting tool
      to evaluate the role of brain angiotensins in different behavior responses. The
      present study was conducted to test the hypothesis that angiotensin-(1-7) [Ang-(1
      7)] and serotonin can modulate anxiety and depression-related behaviors in the
      TGR(ASrAOGEN)680 rats. Therefore, the effect of acute intracerebroventricular
      administration of Ang-(1-7) and intraperitoneal administration of the selective
      serotonin reuptake inhibitor fluoxetine was evaluated in TGR(ASrAOGEN) rats
      subjected to the elevated plus maze (EPM) and forced swimming (FST) tests.
      Transgenic rats spent a lower percentage of time in the open arms of EPM and
      showed a significant increase in the immobility time in FST, indicating that a
      low angiotensinogen level in the brain leads to anxiety-like behavior accompanied
      by a depression-like state. Administration of both, Ang-(1-7) and fluoxetine
      reversed the anxiety- and depressive-like behavior of transgenic rats with low
      brain angiotensinogen, suggesting that this may be, at least in part, related to
      a decreased level of Ang-(1-7) and serotonin in the brain of these animals. 

PMID- 24016840
TI  - Serotonergic receptor mechanisms underlying antidepressant-like action in the
      progesterone withdrawal model of hormonally induced depression in rats.
AB  - Hormonally induced mood disorders such as premenstrual dysphoric disorder (PMDD)
      are characterized by a range of physical and affective symptoms including
      anxiety, irritability, anhedonia, social withdrawal and depression. Studies
      demonstrated rodent models of progesterone withdrawal (PWD) have a high level of
      constructive and descriptive validity to model hormonally-induced mood disorders
      in women. Here we evaluate the effects of several classes of antidepressants in
      PWD female Long-Evans rats using the forced swim test (FST) as a measure of
      antidepressant activity. The study included fluoxetine, duloxetine, amitriptyline
      and an investigational multimodal antidepressant, vortioxetine (5-HT(3), 5-HT(7)
      and 5-HT(1D) receptor antagonist; 5-HT(1B) receptor partial agonist; 5-HT(1A)
      receptor agonist; inhibitor of the serotonin transporter (SERT)). After 14 days
      of administration, amitriptyline and vortioxetine significantly reduced
      immobility in the FST whereas fluoxetine and duloxetine were ineffective. After 3
      injections over 48 h, neither fluoxetine nor duloxetine reduced immobility,
      whereas amitriptyline and vortioxetine significantly reduced FST immobility
      during PWD. When administered acutely during PWD, the 5-HT(1A) receptor agonist,
      flesinoxan, significantly reduced immobility, whereas the 5-HT(1A) receptor
      antagonist, WAY-100635, increased immobility. The 5-HT(3) receptor antagonist,
      ondansetron, significantly reduced immobility, whereas the 5-HT(3) receptor
      agonist, SR-57227, increased immobility. The 5-HT(7) receptor antagonist, SB
      269970, was inactive, although the 5-HT(7) receptor agonist, AS-19, significantly
      increased PWD-induced immobility. None of the compounds investigated
      (ondansetron, flesinoxan and SB-269970) improved the effect of fluoxetine during
      PWD. These data indicate that modulation of specific 5-HT receptor subtypes is
      critical for manipulating FST immobility in this model of hormone-induced
      depression.

PMID- 24016841
TI  - Porous graphitic carbon nanosheets as a high-rate anode material for lithium-ion
      batteries.
AB  - Two-dimensional (2D) porous graphitic carbon nanosheets (PGC nanosheets) as a
      high-rate anode material for lithium storage were synthesized by an easy, low
      cost, green, and scalable strategy that involves the preparation of the PGC
      nanosheets with Fe and Fe3O4 nanoparticles embedded (indicated with
      (Fe&Fe3O4)@PGC nanosheets) using glucose as the carbon precursor, iron nitrate as
      the metal precursor, and a surface of sodium chloride as the template followed by
      the subsequent elimination of the Fe and Fe3O4 nanoparticles from the
      (Fe&Fe3O4)@PGC nanosheets by acid dissolution. The unique 2D integrative features
      and porous graphitic characteristic of the carbon nanosheets with high porosity,
      high electronic conductivity, and outstanding mechanical flexibility and
      stability are very favorable for the fast and steady transfer of electrons and
      ions. As a consequence, a very high reversible capacity of up to 722 mAh/g at a
      current density of 100 mA/g after 100 cycles, a high rate capability (535, 380,
      200, and 115 mAh/g at 1, 10, 20, and 30 C, respectively, 1 C = 372 mA/g), and a
      superior cycling performance at an ultrahigh rate (112 mAh/g at 30 C after 570
      charge-discharge cycles) are achieved by using these nanosheets as a lithium-ion
      battery anode material. 

PMID- 24016842
TI  - Composition of intraperitoneally implanted electrospun conduits modulates
      cellular elastic matrix generation.
AB  - Improving elastic matrix generation is critical to developing functional tissue
      engineered vascular grafts. Therefore, this study pursued a strategy to grow
      autologous tissue in vivo by recruiting potentially more elastogenic cells to
      conduits implanted within the peritoneal cavity. The goal was to determine the
      impacts of electrospun conduit composition and hyaluronan oligomer (HA-o)
      modification on the recruitment of peritoneal cells, and their phenotype and
      ability to synthesize elastic matrix. These responses were assessed as a function
      of conduit intra-peritoneal implantation time. This study showed that the
      blending of collagen with poly(epsilon-caprolactone) (PCL) promotes a faster
      wound healing response, as assessed by trends in expression of macrophage and
      smooth muscle cell (SMC) contractile markers and in matrix deposition, compared
      to the more chronic response for PCL alone. This result, along with the increase
      in elastic matrix production, demonstrates the benefits of incorporating as
      little as 25% w/w collagen into the conduit. In addition, PCR analysis
      demonstrated the challenges in differentiating between a myofibroblast and an SMC
      using traditional phenotypic markers. Finally, the impact of the tethered HA-o is
      limited within the inflammatory environment, unlike the significant response
      found previously in vitro. In conclusion, these results demonstrate the
      importance of both careful control of implanted scaffold composition and the
      development of appropriate delivery methods for HA-o. 

PMID- 24016843
TI  - Soluble silica inhibits osteoclast formation and bone resorption in vitro.
AB  - Several studies have suggested that silicon (Si) may be essential for the normal
      development of connective tissue and the skeleton. Positive effects of Si from
      the diet as well as from Si-containing biomaterials, such as bioactive glass 45S5
      (BG), have been demonstrated. Studies have reported that Si stimulates osteoblast
      proliferation and differentiation. However, the effects of Si on osteoclasts have
      not been directly addressed. The purpose of the present in vitro study was to
      clarify if Si has regulatory effects on osteoclast formation and bone resorption.
      The effects of BG, BG dissolution extracts and Si containing cell culture medium
      were investigated in a mouse calvarial bone resorption assay and osteoclast
      formation assays (mouse bone marrow cultures and RAW264.7 cell cultures). We
      conclude from our results that Si causes significant inhibition of osteoclast
      phenotypic gene expressions, osteoclast formation and bone resorption in vitro.
      In conclusion, the present study suggests that Si has a dual nature in bone
      metabolism with stimulatory effects on osteoblasts and inhibitory effects on
      osteoclasts. This suggested property of Si might be interesting to further
      explore in future biomaterials for treatments of bone defects in patients. 

PMID- 24016844
TI  - Short- and long-term mortality risk associated with the use of antipsychotics
      among 26,940 dementia outpatients: a population-based study.
AB  - OBJECTIVE: To investigate short- and long-term mortality risk associated with the
      use of antipsychotics in dementia outpatients, assessing the risk over specific
      time frames and quantifying the risk by the individual antipsychotics. METHODS:
      This population-based study used data from the Norwegian Prescription Database.
      The study sample included 26,940 dementia outpatients aged 65 years or older
      prescribed antidementia drugs and psychotropics from Norwegian pharmacies between
      2004 and 2010. RESULTS: Cox survival analyses, adjusted for age, gender, mean
      daily defined dose, and severe medical conditions, showed that antipsychotic use
      compared with other psychotropics involved approximately twice the mortality risk
      in outpatients with dementia. Furthermore, these results are consistent for all
      investigated time points after first dispensing the drugs (hazard ratio [HR]30
      days = 2.1 [95% confidence interval {CI}: 1.6-2.9] to HR 730-2,400 days = 1.7
      [95% CI: 1.6-1.9]). Haloperidol was associated with higher mortality risk (HR 30
      days = 1.7 [95% CI: 1.0-3.0] to HR 730-2,400 days = 1.4 [95% CI: 1.0-1.9]) than
      risperidone. CONCLUSION: This first study to observe antipsychotic use and
      mortality in dementia outpatients over more than 6 years clearly shows that
      antipsychotics involve increased short- and long-term mortality risk. Physicians
      may justly consider antipsychotics to be the best option for some dementia
      patients among available nonpharmacologic and pharmacologic treatments. However,
      although causal conclusions are precluded due to limited adjustments in the
      analyses, the findings support the current treatment recommendations that
      antipsychotics should be avoided or used with great caution.

PMID- 24016845
TI  - The Patient Protection and Affordable Care Act: impact on care to patients with
      paediatric and congenital cardiac disease.

PMID- 24016846
TI  - Mega-epsilon waves on 12-lead ECG--just another case of arrhythmogenic right
      ventricular dysplasia/cardiomyopathy?
AB  - Epsilon wave, the post-excitation small squiggles at the beginning of ST segment
      that first named by Fontaine, is a well-known ECG phenomenon frequently
      associated with arrhythmogenic right ventricular dysplasia/cardiomyopathy
      (ARVD/C). Epsilon waves are caused by post excitation of the myocytes in the
      right ventricle due to myocardial scaring. Increasing evidence suggests that
      cardiac sarcoidosis might produce the pathological substrate required for
      production of epsilon waves. Therefore differentiating these two entities is of
      paramount clinical importance. Here we report a case demonstrating mega-epsilon
      wave, right ventricular dilatation and inducible ventricular tachycardia (VT)
      that was initially diagnosed as ARVD/C by the Task Force Criteria. However after
      a thorough evaluation, diagnosis of cardiac sarcoidosis was confirmed by the
      evidence of non-caseating granulomas from endomycardial biopsy. 

PMID- 24016847
TI  - Development of the Animal Management and Husbandry Online Placement Tool.
AB  - The workplace provides veterinary students with opportunities to develop a range
      of skills, making workplace learning an important part of veterinary education in
      many countries. Good preparation for work placements is vital to maximize
      learning; to this end, our group has developed a series of three computer-aided
      learning (CAL) packages to support students. The third of this series is the
      Animal Management and Husbandry Online Placement Tool (AMH OPT). Students need a
      sound knowledge of animal husbandry and the ability to handle the common domestic
      species. However, teaching these skills at university is not always practical and
      requires considerable resources. In the UK, the Royal College of Veterinary
      Surgeons (RCVS) requires students to complete 12 weeks of pre-clinical animal
      management and husbandry work placements or extramural studies (EMS). The aims
      are for students to improve their animal handling skills and awareness of
      husbandry systems, develop communication skills, and understand their future
      clients' needs. The AMH OPT is divided into several sections: Preparation, What
      to Expect, Working with People, Professionalism, Tips, and Frequently Asked
      Questions. Three stakeholder groups (university EMS coordinators, placement
      providers, and students) were consulted initially to guide the content and design
      and later to evaluate previews. Feedback from stakeholders was used in an
      iterative design process, resulting in a program that aims to facilitate student
      preparation, optimize the learning opportunities, and improve the experience for
      both students and placement providers. The CAL is available online and is open
      access worldwide to support students during veterinary school. 

PMID- 24016848
TI  - Manipulating the antigen-specific immune response by the hydrophobicity of
      amphiphilic poly(gamma-glutamic acid) nanoparticles.
AB  - The new generation vaccines are safe but poorly immunogenic, and thus they
      require the use of adjuvants. However, conventional vaccine adjuvants fail to
      induce potent cellular immunity, and their toxicity and side-effects hinder the
      clinical use. Therefore, a vaccine adjuvant which is safe and can induce an
      antigen-specific cellular immunity-biased immune response is urgently required.
      In the development of nanoparticle-based vaccine adjuvants, the hydrophobicity is
      one of the most important factors. It could control the interaction between the
      encapsulated antigens and/or nanoparticles with immune cells. In this study,
      nanoparticles (NPs) composed of amphiphilic poly(gamma-glutamic acid)-graft-L
      phenylalanine ethyl ester (gamma-PGA-Phe) with various grafting degrees of
      hydrophobic side chains were prepared to evaluate the effect of hydrophobicity of
      vaccine carriers on the antigen encapsulation behavior, cellular uptake,
      activation of dendritic cells (DCs), and induction of antigen-specific cellular
      immunity-biased immune responses. These NPs could efficiently encapsulate
      antigens, and the uptake amount of the encapsulated antigen by DCs was dependent
      on the hydrophobicity of gamma-PGA-Phe NPs. Moreover, the activation potential of
      the DCs and the induction of antigen-specific cellular immunity were correlated
      with the hydrophobicity of gamma-PGA-Phe NPs. By controlling the hydrophobicity
      of antigen-encapsulated gamma-PGA-Phe NPs, the activation potential of DCs was
      able to manipulate about 5 to 30-hold than the conventional vaccine, and the
      cellular immunity was about 10 to 40-hold. These results suggest that the
      hydrophobicity of NPs is a key factor for changing the interaction between NPs
      and immune cells, and thus the induction of cellular immunity-biased immune
      response could be achieved by controlling the hydrophobicity of them.

PMID- 24016849
TI  - Imaging of neurosphere oxygenation with phosphorescent probes.
AB  - Multicellular spheroids are useful models of mammalian tissue for studies of cell
      proliferation, differentiation, replacement therapies and drug action. Having a
      size of 100-500 MUm they mimic in vivo micro-environment and characteristic
      gradients of O2, pH and nutrients. We describe the use of cell-penetrating O2
      probes based on phosphorescent Pt-porphyrins to perform high-resolution 2D and 3D
      mapping of O2 in spheroid structures by live cell fluorescence imaging technique.
      Optimised procedures for preparation of neurospheres from cortical neural cells
      isolated from embryonic rat brain, their staining with the phosphorescent O2
      probes NanO2 and MM2 and subsequent analysis of oxygenation on different live
      cell imaging platforms, including widefield and confocal phosphorescence lifetime
      imaging microscopy (PLIM), conventional confocal and two-photon ratiometric
      intensity based O2 detection are presented. This is followed by a series of
      physiological experiments in which oxygenation patterns of the neurospheres are
      correlated with culturing conditions (atmospheric hypoxia and hyperoxia, size,
      growth factors), distribution of stem cells, mature neurons and astrocytes, HIF
      2alpha stabilisation and responses to metabolic stimulation. The O2 imaging
      method allows multiplexing with many conventional fluorescent probes to perform
      multi-parametric imaging analysis of cells in 3D microenvironment. It can be
      applied to other types of spheroids and 3D tissue models.

PMID- 24016850
TI  - The antiviral activity of poly-gamma-glutamic acid, a polypeptide secreted by
      Bacillus sp., through induction of CD14-dependent type I interferon responses.
AB  - Poly-gamma-glutamic acid (gamma-PGA) is an anionic polypeptide secreted by
      Bacillus sp. that has been shown to activate immune cells through interactions
      with toll-like receptor 4 (TLR4). However, its ability to induce the type I
      interferon (IFN) response has not yet been characterized. Here, we demonstrate
      that gamma-PGA induces type I IFN signaling pathway via the TLR4 signaling
      pathway. The induction required both myeloid differentiation factor 2 (MD2) and
      the pattern-recognition receptor CD14, which are two TLR4-associated accessory
      proteins. The gamma-PGA with high molecular weights (2000 and 5000 kDa) was able
      to activate the subsequent signals through TLR4/MD2 to result in dimerization of
      IRF-3, a transcription factor required for IFN gene expression, leading to
      increases in mRNA levels of the type I IFN-response genes, 2'-5' OAS and ISG56.
      Moreover, gamma-PGA (2000 kDa) displayed an antiviral activity against SARS
      coronavirus and hepatitis C virus. Our results identify high-molecular weight
      gamma-PGA as a TLR4 ligand and demonstrate that gamma-PGA requires both CD14 and
      MD2 for the activation of type I IFN responses. Our results suggest that the
      microbial biopolymer gamma-PGA may have therapeutic potential against a broad
      range of viruses sensitive to type I IFNs.

PMID- 24016851
TI  - Suppressing iron oxide nanoparticle toxicity by vascular targeted antioxidant
      polymer nanoparticles.
AB  - The biomedical use of superparamagnetic iron oxide nanoparticles has been of
      continued interest in the literature and clinic. Their ability to be used as
      contrast agents for imaging and/or responsive agents for remote actuation makes
      them exciting materials for a wide range of clinical applications. Recently,
      however, concern has arisen regarding the potential health effects of these
      particles. Iron oxide toxicity has been demonstrated in in vivo and in vitro
      models, with oxidative stress being implicated as playing a key role in this
      pathology. One of the key cell types implicated in this injury is the vascular
      endothelial cells. Here, we report on the development of a targeted polymeric
      antioxidant, poly(trolox ester), nanoparticle that can suppress oxidative damage.
      As the polymer undergoes enzymatic hydrolysis, active trolox is locally released,
      providing a long term protection against pro-oxidant agents. In this work,
      poly(trolox) nanoparticles are targeted to platelet endothelial cell adhesion
      molecules (PECAM-1), which are able to bind to and internalize in endothelial
      cells and provide localized protection against the cytotoxicity caused by iron
      oxide nanoparticles. These results indicate the potential of using poly(trolox
      ester) as a means of mitigating iron oxide toxicity, potentially expanding the
      clinical use and relevance of these exciting systems.

PMID- 24016852
TI  - Cholesteryl hyaluronic acid-coated, reduced graphene oxide nanosheets for anti
      cancer drug delivery.
AB  - Here, we report hyaluronyl reduced graphene oxide (rGO) nanosheets as a tumor
      targeting delivery system for anticancer agents. Hyaluronyl-modified rGO
      nanosheets were prepared by synthesizing cholesteryl hyaluronic acid (CHA) and
      using it to coat rGO nanosheets, yielding CHA-rGO. Compared with rGO, CHA-rGO
      nanosheets showed increased colloidal stability under physiological conditions
      and improved in vivo safety, with a survival rate of 100% after intravenous
      administration of 40 mg/kg in mice. The doxorubicin (Dox) loading capacity of CHA
      rGO was 4-fold greater than that of rGO. Uptake of Dox by CD44-overexpressing KB
      cells was higher for CHA-rGO than for rGO, and was decreased in the presence of
      hyaluronic acid through competition for CD44 receptor binding. After intravenous
      administration in tumor-bearing mice, CHA-rGO/Dox showed higher tumor
      accumulation than rGO/Dox. The in vivo antitumor efficacy of Dox delivered by CHA
      rGO was significantly increased compared with free Dox or rGO/Dox. In CHA-rGO/Dox
      treated mice, tumor weights were reduced to 14.1% +/- 0.1% of those in untreated
      mice. Our findings indicate that CHA-rGO nanosheets possess greater stability,
      safety, drug-loading capacity, and CD44-mediated delivery of Dox than rGO
      nanosheets. These beneficial properties of CHA-rGO improved the distribution of
      Dox to tumors and facilitated the cellular uptake of Dox by CD44-overexpressing
      tumor cells, resulting in enhanced anticancer effects.

PMID- 24016853
TI  - A silk fibroin based hepatocarcinoma model and the assessment of the drug
      response in hyaluronan-binding protein 1 overexpressed HepG2 cells.
AB  - Microenvironment around tumor cells plays an important role in its malignancy or
      invasiveness. Hyaluronan (HA), a major component of extracellular matrix is found
      to be elevated in most of cancerous niche/microenvironment and performs
      regulatory role in the progression of tumors and metastasis. Overexpression of
      the hyaladherin, hyaluronan-binding protein 1 (HABP1) in the hepatocarcinoma
      cells (HepG2) termed as HepR21 leads to enhanced cell proliferation with
      increased HA 'pool' associated with HA 'cables' indicating elevated tumorous
      potential under 2D culture conditions. For in vitro experimentation, scaffold
      based three dimensional niche modeling may have greater acceptance than
      conventional 2D culture condition. Thus, we have examined the influence of
      intrinsic properties of non-mulberry tropical tasar silk fibroin on the HepR21
      cells in order to develop a 3D hepatocarcinoma construction to act as model. The
      scaffold of tasar silk fibroin of Antheraea mylitta when efficiently loaded with
      transformed hepatocarcinoma cells, HepR21; exhibits enhanced adhesiveness,
      viability, metabolic activity, proliferation and enlarged cellular morphology in
      3D compared to its parent cell line HepG2, supporting the earlier observation
      made in 2D system. In addition, formation of multicellular aggregates, the
      indicator of tumor progression is also revealed in silk based 3D culture
      conditions. Further, the use of 4-MU (a hyaluronan synthase inhibitor) on HepR21
      cells reduces the HA level and downregulates the expression of growth promoting
      factors like pAKT and PKC; while upregulating the expression of the tumor
      suppressor p53. Thus, 4-MU efficiently reduces the tumor potency associated with
      increased HA pool as well as HA cables and the effect of 4-MU doubling up as an
      anticancer agent in 2D and 3D are also comparable. The in vitro 3D multicellular
      model demonstrates the insight of hepatocarcinoma progression and offers the
      predictability of cellular response to transfection efficacy, drug treatment and
      therapeutic intervention.

PMID- 24016854
TI  - The use of ASCs engineered to express BMP2 or TGF-beta3 within scaffold
      constructs to promote calvarial bone repair.
AB  - Calvarial bone healing is difficult and grafts comprising adipose-derived stem
      cells (ASCs) and PLGA (poly(lactic-co-glycolic acid)) scaffolds barely heal
      rabbit calvarial defects. Although calvarial bone forms via intramembranous
      ossification without cartilage templates, it was suggested that
      chondrocytes/cartilages promote calvarial healing, thus we hypothesized that
      inducing ASCs chondrogenesis and endochondral ossification involving cartilage
      formation can improve calvarial healing. To evaluate this hypothesis and
      selectively induce osteogenesis/chondrogenesis, rabbit ASCs were engineered to
      express the potent osteogenic (BMP2) or chondrogenic (TGF-beta3) factor, seeded
      into either apatite-coated PLGA or gelatin sponge scaffolds, and allotransplanted
      into critical-size calvarial defects. Among the 4 ASCs/scaffold constructs,
      gelatin constructs elicited in vitro chondrogenesis, in vivo osteogenic
      metabolism and calvarial healing more effectively than apatite-coated PLGA,
      regardless of BMP2 or TGF-beta3 expression. The BMP2-expressing ASCs/gelatin
      triggered better bone healing than TGF-beta3-expressing ASCs/gelatin, filling ~
      86% of the defect area and ~ 61% of the volume at week 12. The healing proceeded
      via endochondral ossification, instead of intramembranous pathway, as evidenced
      by the formation of cartilage that underwent osteogenesis and hypertrophy. These
      data demonstrated ossification pathway switching and significantly augmented
      calvarial healing by the BMP2-expressing ASCs/gelatin constructs, and underscored
      the importance of growth factor/scaffold combinations on the healing efficacy and
      pathway.

PMID- 24016855
TI  - Intestinal mucosa permeability following oral insulin delivery using core shell
      corona nanolipoparticles.
AB  - Chitosan nanoparticles (NC) have excellent capacity for protein entrapment,
      favorable epithelial permeability, and are regarded as promising nanocarriers for
      oral protein delivery. Herein, we designed and evaluated a class of core shell
      corona nanolipoparticles (CSC) to further improve the absorption through enhanced
      intestinal mucus penetration. CSC contains chitosan nanoparticles as a core
      component and pluronic F127-lipid vesicles as a shell with hydrophilic chain and
      polyethylene oxide PEO as a corona. These particles were developed by hydration
      of a dry pluronic F127-lipid film with NC suspensions followed by extrusion.
      Insulin nested inside CSC was well protected from enzymatic degradation. Compared
      with NC, CSC exhibited significantly higher efficiency of mucosal penetration
      and, consequently, higher cellular internalization of insulin in mucus secreting
      E12 cells. The cellular level of insulin after CSC treatment was 36-fold higher
      compared to treatment with free insulin, and 10-fold higher compared to NC. CSC
      significantly facilitated the permeation of insulin across the ileum epithelia,
      as demonstrated in an ex vivo study and an in vivo absorption study. CSC
      pharmacological studies in diabetic rats showed that the hypoglycemic effects of
      orally administrated CSC were 2.5-fold higher compared to NC. In conclusion, CSC
      is a promising oral protein delivery system to enhance the stability, intestinal
      mucosal permeability, and oral absorption of insulin.

PMID- 24016856
TI  - The influence of substrate topography on the migration of corneal epithelial
      wound borders.
AB  - Currently available artificial corneas can develop post-implant complications
      including epithelial downgrowth, infection, and stromal melting. The likelihood
      of developing these disastrous complications could be minimized through improved
      formation and maintenance of a healthy epithelium covering the implant. We
      hypothesize that this epithelial formation may be enhanced through the
      incorporation of native corneal basement membrane biomimetic chemical and
      physical cues onto the surface of the keratoprosthesis. We fabricated hydrogel
      substrates molded with topographic features containing specific bio-ligands and
      developed an in vitro wound healing assay. In our experiments, the rate of
      corneal epithelial wound healing was significantly increased by 50% in hydrogel
      surfaces containing topographic features, compared to flat surfaces with the same
      chemical attributes. We determined that this increased healing is not due to
      enhanced proliferation or increased spreading of the epithelial cells, but to an
      increased active migration of the epithelial cells. These results show the
      potential benefit of restructuring and improving the surface of artificial
      corneas to enhance epithelial coverage and more rapidly restore the formation of
      a functional epithelium.

PMID- 24016857
TI  - Calvarial defect healing by recruitment of autogenous osteogenic stem cells using
      locally applied simvastatin.
AB  - Local statins implant has been shown to promote bone healing, the underlying
      mechanisms are unclear. The purpose of this study was to test the effect of local
      simvastatin implant on bone defect healing; to evaluate the mobilization,
      migration, and homing of bone marrow-derived mesenchymal stem cells (BMSCs) and
      endothelial progenitor cells (EPCs) induced by simvastatin. We found that local
      simvastatin implant increased bone formation by 51.8% (week 6) and 64.8% (week
      12) compared with polyglycolic acid controls (P < 0.01), as verified by X-ray,
      CT, and histology. Simvastatin increased migration capacity of BMSCs and EPCs in
      vitro (P < 0.05). Local simvastatin implant increased mobilization of EPCs to the
      peripheral blood by 127% revealed by FACS analysis (P < 0.01), and increased
      osteogenic BMSCs to the peripheral blood dramatically revealed by Alizarin Red-S
      staining for mineralized nodules formation. Pre-transplanted GFP-transfected
      BMSCs as a tracing cell and bioluminescence imaging revealed that local
      simvastatin implant recruited GFP-labeled BMSC. Also, local simvastatin implant
      induced the HIF-1alpha and BMP-2 expression. In conclusion, local simvastatin
      implantation promotes bone defect healing, where the underlying mechanism appears
      to involve the higher expression of HIF-1alpha and BMP-2, thus recruit autogenous
      osteogenic and angiogenetic stem cells to the bone defect area implanted with
      simvastatin.

PMID- 24016858
TI  - Nanodiamonds-mediated doxorubicin nuclear delivery to inhibit lung metastasis of
      breast cancer.
AB  - Lung metastasis is one of the greatest challenges for breast cancer treatment.
      Here, a nanodiamonds (NDs)-mediated doxorubicin (DOX) delivery system was first
      designed to inhibit the lung metastasis of breast cancer effectively. DOX was non
      covalently bound to NDs via physical adsorption in an aqueous solution, then DSPE
      PEG 2K was coated to the NDs-DOX complex (NDX) to increase the dispersibility and
      prolong the circulation time. DSPE-PEG 2K coating NDX (DNX) displayed high drug
      loading and excellent ability to deliver DOX to the nucleus, thereby
      significantly enhancing cytotoxicity and inducing cell apoptosis. Furthermore,
      DNX showed good histocompatibility and could improve drug accumulation in lung,
      as a result, markedly inhibited the lung metastasis of breast cancer. The high
      anti-metastasis efficacy with the decreased systemic toxicity suggested that DNX
      could be a promising drug delivery system for the therapy of lung metastasis of
      breast cancer. 

PMID- 24016859
TI  - Vasopeptidase-activated latent ligands of the histamine receptor-1.
AB  - Whether peptidases present in vascular cells can activate prodrugs active on
      vascular cells has been tested with 2 potential latent ligands of the histamine
      H1 receptor (H1R). First, a peptide consisting of the antihistamine cetirizine
      (CTZ) condensed at the N-terminus of epsilon-aminocaproyl-bradykinin (epsilonACA
      BK) was evaluated for an antihistamine activity that could be revealed by
      degradation of the peptide part of the molecule. CTZ-epsilonACA-BK had a
      submicromolar affinity for the BK B2 receptor (B2R; IC50 of 590 nM, [(3)H]BK
      binding competition), but a non-negligible affinity for the human H1 receptor
      (H1R; IC50 of 11 MUM for [(3)H]pyrilamine binding). In the human isolated
      umbilical vein, a system where both endogenous B2R and H1R mediate strong
      contractions, CTZ-epsilonACA-BK exerted mild antagonist effects on histamine
      induced contraction that were not modified by omapatrilat or by a B2R antagonist
      that prevents endocytosis of the BK conjugate. Cells expressing recombinant ACE
      or B2R incubated with CTZ-epsilonACA-BK did not release a competitor of
      [(3)H]pyrilamine binding to H1Rs. Thus, there is no evidence that CTZ-epsilonACA
      BK can release free cetirizine in biological environments. The second prodrug was
      a blocked agonist, L-alanyl-histamine, potentially activated by aminopeptidase N
      (APN). This compound did not compete for [(3)H]pyrilamine binding to H1Rs. The
      human umbilical vein contractility assay responded to L-alanyl-histamine (EC50
      54.7 MUM), but the APN inhibitor amastatin massively (17-fold) reduced its
      apparent potency. Amastatin did not influence the potency of histamine as a
      contractile agent. One of the 2 tested latent H1R ligands, L-alanyl-histamine,
      supported the feasibility of pro-drug activation by vascular ectopeptidases.

PMID- 24016861
TI  - Cell tracking in microscopic video using matching and linking of bipartite
      graphs.
AB  - Automated visual tracking of cells from video microscopy has many important
      biomedical applications. In this paper, we track human monocyte cells in a
      fluorescent microscopic video using matching and linking of bipartite graphs.
      Tracking of cells over a pair of frames is modeled as a maximum cardinality
      minimum weight matching problem for a bipartite graph with a novel cost function.
      The tracking results are further refined using a rank-based filtering mechanism.
      Linking of cell trajectories over different frames are achieved through
      composition of bipartite matches. The proposed solution does not require any
      explicit motion model, is highly scalable, and, can effectively handle the entry
      and exit of cells. Our tracking accuracy of (97.97+/-0.94)% is superior than
      several existing methods [(95.66+/-2.39)%, (94.42+/-2.08)%, (81.22+/-5.75)%,
      (78.31+/-4.70)%] and is highly comparable (98.20+/-1.22)% to a recently published
      algorithm.

PMID- 24016862
TI  - pairheatmap: comparing expression profiles of gene groups in heatmaps.
AB  - This paper presents a new visualization software called pairheatmap, which is
      able to generate and compare two heatmaps so as to compare expression patterns of
      gene groups. It adds a conditioning variable such as time to the heatmap, and
      provides separate clustering for row groups in the first heatmap in order to
      visualize pattern changes between two heatmaps. pairheatmap is developed in R
      statistical environment. It provides: (1) the flexible framework for comparing
      two heatmaps; and (2) high-quality figures based on R package grid. The general
      architecture can be efficiently incorporated into bioinformatics pipeline. The
      package and user documentation are free to download at http://cran.r
      project.org/web/packages/pairheatmap/index.html. 

PMID- 24016860
TI  - Differential expression of CD148 on leukocyte subsets in inflammatory arthritis.
AB  - INTRODUCTION: Monocytic cells play a central role in the aetiology of rheumatoid
      arthritis, and manipulation of the activation of these cells is an approach
      currently under investigation to discover new therapies for this and associated
      diseases. CD148 is a transmembrane tyrosine phosphatase that is highly expressed
      in monocytes and macrophages and, since this family of molecules plays an
      important role in the regulation of cell activity, CD148 is a potential target
      for the manipulation of macrophage activation. For any molecule to be considered
      a therapeutic target, it is important for it to be increased in activity or
      expression during disease. METHODS: We have investigated the expression of CD148
      in two murine models of arthritis and in joints from rheumatoid arthritis (RA)
      patients using real-time PCR, immunohistochemistry, and studied the effects of
      proinflammatory stimuli on CD148 activity using biochemical assays. RESULTS: We
      report that CD148 mRNA is upregulated in diseased joints of mice with collagen
      induced arthritis. Furthermore, we report that in mice CD148 protein is highly
      expressed in infiltrating monocytes of diseased joints, with a small fraction of
      T cells also expressing CD148. In human arthritic joints both T cells and
      monocytes expressed high levels of CD148, however, we show differential
      expression of CD148 in T cells and monocytes from normal human peripheral blood
      compared to peripheral blood from RA and both normal and RA synovial fluid.
      Finally, we show that synovial fluid from rheumatoid arthritis patients
      suppresses CD148 phosphatase activity. CONCLUSIONS: CD148 is upregulated in
      macrophages and T cells in human RA samples, and its activity is enhanced by
      treatment with tumour necrosis factor alpha (TNFalpha), and reduced by synovial
      fluid or oxidising conditions. A greater understanding of the role of CD148 in
      chronic inflammation may lead to alternative therapeutic approaches to these
      diseases.

PMID- 24016863
TI  - Association between Attention-Deficit Hyperactivity Disorder in childhood and
      schizophrenia later in adulthood.
AB  - PURPOSE: To estimate the risk of schizophrenia in adulthood among children and
      adolescents with ADHD compared to the background population. SUBJECTS/MATERIALS
      AND METHODS: Two hundred and eight youths with ADHD (183 boys; 25 girls) were
      followed prospectively. Diagnoses of schizophrenia were obtained from The Danish
      Psychiatric Central Register. The relative risk (RR) of schizophrenia for cases
      with ADHD, compared to the normal population, was calculated as risk ratios.
      Hazard ratios (HR's) by Cox regression were calculated in the predictor analyses.
      RESULTS: Mean age for ADHD cases at follow-up was 31.1years. Schizophrenia
      diagnoses were given to 3.8% of these cases. Compared to the general population,
      RR of schizophrenia in cases with ADHD was 4.3 (95% CI 1.9-8.57). DISCUSSION AND
      CONCLUSION: This prospective follow-up study found children with ADHD to be at
      higher risk of later schizophrenia than controls. If replicated, these results
      warrant increased focus on the possible emergence symptoms of schizophrenia or
      schizophreniform psychosis during clinical follow-up of patients with ADHD.

PMID- 24016864
TI  - The association between depressive symptoms, cognitive function, and inflammation
      in major depression.
AB  - The purpose of this study was to assess the association between IL-6 and CRP with
      depressive items and cognitive function. We included 112 outpatients with major
      depression from an exercise trial and 57 healthy controls. IL-6, high sensitive
      CRP (hsCRP), and cognitive function were assessed in all subjects. After baseline
      assessment, patients were randomised to either a 3months exercise intervention or
      an exercise control group. Post-intervention IL-6, hsCRP, depressive symptoms,
      and cognitive function were reassessed in the patient group. IL-6 and hsCRP were
      significantly increased in depressed patients compared to healthy controls
      (p=0.02 and 0.04). These differences were no longer significant after adjustment
      for lifestyle associated variables. We found no association between immune
      markers and specific depressive symptoms at baseline or as change over time.
      Regarding the cognitive tests, IL-6 was positively associated with Serial sevens
      (p=0.008) and hsCRP was inversely associated with Trail making A (p=0.02) and
      design fluency (p=0.001) at baseline. At 3months follow-up IL-6 and hsCRP levels
      did not significantly change from baseline and did not differ between the two
      patient groups. Depression scores was lower compared to baseline but did not
      differ between groups. Combining the two groups, a decrease in IL-6 was
      associated to decreased verbal fluency (p=0.02), and a decrease in hsCRP was
      associated with improvement in Trail making A (p=0.005). In conclusion, the level
      of IL-6 and hsCRP was increased in depressed outpatients but was not associated
      to specific depressive symptoms. In terms of cognitive function, we found that
      higher hsCRP levels were associated to lower psychomotor speed both at baseline
      and at follow-up. 

PMID- 24016865
TI  - Influence of a probiotic lactobacillus strain on the intestinal ecosystem in a
      stress model mouse.
AB  - Daily exposure to stressful situations affects the health of humans and animals.
      It has been shown that psychological stress affects the immune system and can
      exacerbate diseases. Probiotics can act as biological immunomodulators in healthy
      people, increasing both intestinal and systemic immune responses. The use of
      probiotics in stress situations may aid in reinforcing the immune system. The aim
      of this study was to evaluate the effect of a probiotic bacterium on the gut
      immune system of mice that were exposed to an experimental model of stress
      induced by food and mobility restriction. The current study focused on immune
      cells associated with the lamina propria of the intestine, including CD4+ and
      CD8+ T lymphocytes, CD11b+ macrophages, CD11c+ dendritic cells, and IgA+ B
      lymphocytes, as well as the concentrations of secretory IgA (S-IgA) and cytokine
      interferon gamma (INF-gamma in intestinal fluid. We also evaluated the
      probiotic's influence on the gut microbiota. Probiotic administration increased
      IgA producing cells, CD4+ cells in the lamina propria of the small intestine, and
      S-IgA in the lumen; it also reduced the levels of IFN-gamma that had increased
      during stress and improved the intestinal microbiota as measured by an increase
      in the lactobacilli population. The results obtained from administration of the
      probiotic to stressed mice suggest that the use of food containing these
      microorganisms may work as a palliative to reinforce the immune system. 

PMID- 24016866
TI  - Decorin inhibits angiogenic potential of choroid-retinal endothelial cells by
      downregulating hypoxia-induced Met, Rac1, HIF-1alpha and VEGF expression in
      cocultured retinal pigment epithelial cells.
AB  - Choroidal neovascularization (CNV) is one of the most common causes of severe
      vision loss. Decorin, a multiple receptor tyrosine kinase inhibitor, has been
      recently shown to play an important regulatory role in angiogenic response. This
      study aims to investigate whether the overexpression of decorin in retinal
      pigment epithelial (RPE) cells under hypoxia alters the in vitro angiogenic
      ability of cocultured choroid-retinal endothelial cells and to explore the
      possible mechanisms involved. Human RPE cells (ARPE-19) were subjected to hypoxia
      with or without decorin pretreatment, and RNA interference technique was used to
      knock down the Met gene in ARPE-19 cells. Cell viability was determined using the
      Cell Counting Kit-8 assay. Expression of Met, Rac1 and hypoxia-inducible factor-1
      alpha (HIF-1alpha) was evaluated by western blot and quantitative real-time
      polymerase chain reaction (qRT-PCR). Vascular endothelial growth factor (VEGF)
      expression was evaluated by enzyme-linked immunosorbent assay (ELISA) and qRT
      PCR. We then constructed a recombinant lentiviral vector carrying the decorin
      gene to transduce ARPE-19 cells. The overexpression of decorin in transduced RPE
      cells was confirmed by qRT-PCR and western blot. The transduced RPE cells were
      then cocultured with rhesus macaque choroid-retinal endothelial cells (RF/6A) in
      a transwell coculture system to observe the effects of decorin overexpression in
      ARPE-19 cells on the proliferation, migration and tube formation of RF/6A cells.
      In response to hypoxia, the VEGF concentrations in the culture supernatants
      increased greatly at 24 and 48 h, and this effect was inhibited significantly and
      nearly equally in the presence of 50-200 nM decorin. Decorin pretreatment before
      hypoxia exposure effectively reduced the hypoxia-induced expression of Met, Rac1,
      HIF-1alpha and VEGF in ARPE-19 cells. Transfection of small interfering RNA
      against Met to ARPE-19 cells also resulted in significant downregulation of Rac1,
      HIF-1alpha and VEGF under hypoxia, and this effect was similar to that noted with
      decorin pretreatment alone or with their combination. Results from the coculture
      system showed that the overexpression of decorin in ARPE-19 cells significantly
      inhibited the proliferation, migration and tube formation of RF/6A cells. These
      results indicate that Met pathway activation plays an important role in the
      upregulation of VEGF in RPE cells under hypoxia. Decorin may interfere with
      angiogenesis by downregulating hypoxia-induced Met, Rac1, HIF-1alpha and VEGF
      expression in RPE cells, which suggests a potential strategy for the inhibition
      of CNV. 

PMID- 24016867
TI  - Whole genome expression profiling of normal human fetal and adult ocular tissues.
AB  - To study growth and development of ocular tissues, gene expression patterns in
      normal human fetal versus adult eyes were compared. Human retina/retinal pigment
      epithelium, choroid, sclera, optic nerve* and cornea* tissues were dissected from
      fetal (24 week gestational age) (N = 9; *N = 6), and adult (N = 6) normal donor
      eyes. The Illumina((r)) whole genome expression microarray platform was used to
      assess differential expression. Statistical significance for all comparisons was
      determined using the Benjamin and Hochberg False Discovery Rate (FDR, 5%).
      Significant gene expression fold changes > 1.5 were found in adult versus fetal
      retina/RPE (N = 1185), choroid (N = 6446), sclera (N = 1349), and cornea (N =
      3872), but not optic nerve. Genes showing differential expression were assessed
      using Ingenuity Pathway Analysis (IPA) for enriched functions and canonical
      pathways. In all tissues, development, cell death/growth, cancer functions, and
      signaling canonical pathways were enriched. There was also a general trend of
      down-regulation of collagen genes in adult tissues. 

PMID- 24016868
TI  - Presence of native limbal stromal cells increases the expansion efficiency of
      limbal stem/progenitor cells in culture.
AB  - Niche factors are important in the maintenance and regulation of stem cells.
      Limbal stromal cells are potentially a component of limbal stem cell (LSC) niche.
      We investigated the role of the limbal stromal cells in the ex vivo expansion of
      limbal stem/progenitor cells. Limbal epithelial cells were cultured as single
      cell suspension and cell clusters from dispase II or collagenase A (ColA), or
      tissue explant. ColA isolated limbal stromal cells along with limbal epithelial
      cells. In the presence of limbal stromal cells, a higher absolute number of
      p63alpha(bright) cells (p < 0.05) and a higher proportion of K14 positive
      epithelial cells were obtained from both ColA and explant tissue cultures.
      Expansion of the stem/progenitor population from dispase isolation was more
      efficient in the form of cell clusters than single cell suspension based on the
      absolute number of p63alpha(bright) cells. Expansion of the stem cell population
      is similar in the single cell and cell cluster cultures that are derived from
      ColA isolation. Our finding suggests that limbal stromal cells and an intact cell
      cell contact help to maintain LSCs in an undifferentiated state in vitro during
      expansion. 

PMID- 24016869
TI  - Mycoplasma feriruminatoris sp. nov., a fast growing Mycoplasma species isolated
      from wild Caprinae.
AB  - Five Mycoplasma strains from wild Caprinae were analyzed: four from Alpine ibex
      (Capra ibex) which died at the Berlin Zoo between 1993 and 1994, one from a Rocky
      Mountain goat collected in the USA prior to 1987. These five strains represented
      a population different from the populations belonging to the 'Mycoplasma mycoides
      cluster' as tested using multi locus sequence typing, Matrix-assisted laser
      desorption/ionization time of flight mass spectrometry analysis and DNA-DNA
      hybridization. Analysis of the 16S rRNA gene (rrs), genomic sequence based in
      silico as well as laboratory DNA-DNA hybridization, and the analysis of
      phenotypic traits in particular their exceptionally rapid growth all confirmed
      that they do not belong to any Mycoplasma species described to date. We therefore
      suggest these strains represent a novel species, for which we propose the name
      Mycoplasma feriruminatoris sp. nov. The type strain is G5847(T) (=DSM
      26019(T)=NCTC 13622(T)) [corrected].

PMID- 24016870
TI  - Elevated CSF1 serum concentration predicts poor overall survival in women with
      early breast cancer.
AB  - Colony-stimulating factor 1 (CSF1) is a key regulator of mammary gland
      development, and a modulator of tissue macrophages. Expression of the CSF1
      receptor gene C-FMS (CSF1R) is strongly associated with poor outcome in breast
      cancer and results in tumor cell invasiveness and pro-metastatic behavior in
      vitro. However, CSF1's role as a predictive factor in breast cancer remains
      unclear. We have prospectively measured circulating CSF1 using ELISA in 572 women
      with early breast cancer and in 688 women with benign breast lesions, and
      correlated these concentrations with overall survival (OS), nodal status, and
      other clinical and histological parameters. Serum CSF1 concentrations were
      significantly elevated in patients with early breast cancer when compared with
      those with benign tumors (P<0.0001). Within breast cancer patients, CSF1 was
      higher in women with axillary lymph nodes (P=0.03). Serum CSF1 correlated with
      tumor size (P=0.002), age (P<0.001), and Ki67 expression (P=0.006). Log CSF1
      serum concentrations were predictive of poor survival in both univariate (hazard
      ratio (HR): 3.77, 95% CI: 1.65-8.65, P=0.002) and multivariate analyses (HR: 3.1,
      95% CI: 1.03-9.33, P=0.04). Post- but not premenopausal women with CSF1 serum
      concentrations >873  pg/ml experienced a significantly poorer outcome (P=0.004
      log-rank test). Serum CSF1 concentrations are elevated in women with malignant
      breast tumors. In early breast cancer, elevated serum CSF1 is associated with
      nodal involvement, and in postmenopausal women also with poor OS.

PMID- 24016871
TI  - Study that supports mammography for women under 50 is criticised.

PMID- 24016872
TI  - Dynamic distribution of potassium in sugarcane.
AB  - In this work the distribution of potassium in sugarcane has been studied during
      its growth. The soil was prepared with natural fertilizers prepared with
      sugarcane bagasse. For the measurement of potassium concentration in each part of
      the plant, gamma-ray spectrometry was used to measure gamma-rays emitted from the
      radioisotope (40)K. The concentrations of potassium in roots, stems and leaves
      were measured every two to three months beginning about five months after
      planting the sugarcane. The results show a higher concentration of potassium at
      the beginning of plant development and over time, there is an oscillatory
      behavior in this concentration in each part of the plant, reaching a lower
      concentration in the adult plant. To describe the evolution of potassium
      distribution in sugarcane we proposed a phenomenological model assuming that the
      potassium incorporation rate is proportional to the difference between the
      element concentration in the plant and a very long term equilibrium value and it
      is coupled to a resource-limited growth model. The proposed model succeeded in
      interpreting the results for the potassium distribution in stems and leaves
      during the sugarcane growth. 

PMID- 24017951
TI  - Endovascular treatment of intracranial dural arteriovenous fistulas.

PMID- 24017952
TI  - Technical note regarding immediate titanium mesh cranioplasty for postcraniotomy
      infections.

PMID- 24017953
TI  - From localization to pathways: the continuing evolution of diffusion tensor
      imaging.

PMID- 24017954
TI  - Diffusion tensor imaging is a research and educational tool, but not yet a
      clinical tool.

PMID- 24017955
TI  - Are hyperlipidemia and autoimmune diseases synergistic in Moyamoya disease
      pathophysiology? Insight from the Midwest.

PMID- 24017956
TI  - Teamwork mentality in neurosurgical teams to improve patient safety.

PMID- 24017957
TI  - "Artifactual fracture-subluxation" of cervical spine in computed tomography
      screening sans plain radiographs.
AB  - BACKGROUND CONTEXT: Computed tomography (CT) has become the sole modality of
      screening for cervical injury in polytrauma because of the high sensitivity,
      speed, and convenience, thereby eliminating the need for plain radiographs.
      PURPOSE: We report two cases of misleading artifactual fracture-subluxation of
      cervical spine in CT, which could have resulted in needless treatment, and
      describe its characteristics. STUDY DESIGN: Case report and review. METHODS: Two
      patients who were initially diagnosed with fracture-subluxation on screening CT
      cervical spine were later noted to have motion artifacts and were reviewed.
      RESULTS: The artifactual nature of the supposed fracture-subluxation was unmasked
      by the soft-tissue findings of obscuration in sagittal reconstruction and
      duplication in axial images, along with the presence of double bony margins.
      CONCLUSIONS: Motion artifact in cervical CT screening can lead to a misdiagnosis
      of fracture subluxation. Duplication of soft tissue is highly suggestive of this
      motion artifact, and an additional single lateral plain radiograph may avert this
      pitfall.

PMID- 24017958
TI  - Long-term follow-up of a case of aneurysmal bone cyst in the lumbar spine.
AB  - BACKGROUND CONTEXT: Aneurysmal bone cyst (ABC) in the spine is relatively rare,
      so little is known about the natural history of the disease. PURPOSE: The purpose
      of this study was to describe a spinal ABC that was followed for an extended
      period from lesion enlargement to spontaneous regression. STUDY DESIGN: Case
      report. METHODS: A 63-year-old woman had a 1-year-long history of mild low back
      and bilateral leg pain without any significant neurologic deficits caused by
      lumbar spinal stenosis. At her first visit to our hospital, magnetic resonance
      imaging (MRI) showed a small cystic lesion on the left side of the L5 vertebral
      body. The patient's clinical symptom progression and MRI and computed tomography
      evaluations were reported for >13 years. RESULTS: After 6 years, the cystic
      lesion enlarged significantly and extended into the left pedicle and transverse
      process of the L5 vertebra. The lesion was diagnosed as an ABC based on
      multilocular cysts with fluid-fluid levels on MRI and bony septations on computed
      tomography. Thirteen years after the first visit, the lesion regressed
      spontaneously without a clear reason, such as biopsy or fracture, and most of the
      lesion was replaced by fatty marrow. The patient's symptoms stabilized without
      neurologic deterioration during the follow-up period. CONCLUSIONS: Although
      spinal ABC is an expandable cystic lesion, we should consider that such a lesion
      in an elderly patient could spontaneously regress.

PMID- 24017959
TI  - Reoperation rate after surgery for lumbar spinal stenosis without
      spondylolisthesis: a nationwide cohort study.
AB  - BACKGROUND CONTEXT: Lumbar spinal stenosis is one of the most common degenerative
      spine diseases. Surgical options are largely divided into decompression only and
      decompression with arthrodesis. Recent randomized trials showed that surgery was
      more effective than nonoperative treatment for carefully selected patients with
      lumbar stenosis. However, some patients require reoperation because of
      complications, failure of bony fusion, persistent pain, or progressive
      degenerative changes, such as adjacent segment disease. In a previous population
      based study, the 10-year reoperation rate was 17%, and fusion surgery was
      performed in 10% of patients. Recently, the lumbar fusion surgery rate has
      doubled, and a substantial portion of the reoperations are associated with a
      fusion procedure. With the change in surgical trends, the longitudinal surgical
      outcomes of these trends need to be reevaluated. PURPOSE: To provide the
      longitudinal reoperation rate after surgery for spinal stenosis and to compare
      the reoperation rates between decompression and fusion surgeries. STUDY
      DESIGN/SETTING: Retrospective cohort study using national health insurance data.
      PATIENT SAMPLE: A cohort of patients who underwent initial surgery for lumbar
      stenosis without spondylolisthesis in 2003. OUTCOME MEASURES: The primary end
      point was any type of second lumbar surgery. Cox proportional hazards regression
      modeling was used to compare the adjusted reoperation rates between decompression
      and fusion surgeries. METHODS: A national health insurance database was used to
      identify a cohort of patients who underwent an initial surgery for lumbar
      stenosis without spondylolisthesis in 2003; a total of 11,027 patients were
      selected. Individual patients were followed for at least 5 years through their
      encrypted unique resident registration number. After adjusting for confounding
      factors, the reoperation rates for decompression and fusion surgery were
      compared. RESULTS: Fusion surgery was performed in 20% of patients. The
      cumulative reoperation rate was 4.7% at 3 months, 7.2% at 1 year, 9.4% at 2
      years, 11.2% at 3 years, 12.5% at 4 years, and 14.2% at 5 years. The adjusted
      reoperation rate was not different between decompression and fusion surgeries
      (p=.82). The calculated reoperation rate was expected to be 22.9% at 10 years.
      CONCLUSIONS: The reoperation rate was not different between decompression and
      fusion surgeries. With current surgical trends, the reoperation rate appeared to
      be higher than in the past, and consideration of this problem is required.

PMID- 24017960
TI  - An evaluation of heart rate variability and its modifying factors in children
      with type 1 diabetes.
AB  - OBJECTIVE: To evaluate heart rate variability by Holter monitoring in type 1
      diabetic children compared with a healthy control group and determine the factors
      modifying heart rate variability. METHODS: This was designed as a prospective
      study comparing 28 patients, diagnosed with type 1 diabetes and under follow-up,
      with 27 healthy control group subjects. RESULTS: The patients were aged 9.9 +/-
      4.2 years in the diabetic group, including 13 (46.5%) girls and 15 (53.5%) boys.
      The healthy control group comprised 20 (74%) girls and seven boys (26%) with an
      average age of 8.6 +/- 3.7 years. The search for factors modifying heart rate
      variability yielded the following correlations: for the time-dependent variables,
      negative between age and both average and maximal heart rate (r = -0.263 and 
      0.460, respectively), negative between haemoglobin A1c and percentage of
      differences between adjacent RR intervals >50 ms, positive between diabetes
      duration and square root of the mean of the sum of squares of differences between
      adjacent NN intervals. The average heart rate and percentage of differences
      between adjacent RR intervals >50 ms was significantly higher in the girls than
      the boys in all groups. With regard to the frequency-dependent factors affecting
      heart rate variability, correlations were found between haemoglobin A1c level and
      both total power and very low frequency (r = -0.751 and -0.644) and between very
      low frequency and diabetes duration. CONCLUSION: A reduction in heart rate
      variability parameters was observed in type 1 diabetes mellitus patients who had
      a long disease duration or were poorly controlled, as compared with healthy
      controls.

PMID- 24017961
TI  - Is it possible to diagnose malignancy from fluid in cystic ovarian tumors?
AB  - OBJECTIVE: p53 gene mutations are frequently identified in ovarian cancer tissue.
      The aim of this study was to investigate whether wild type or mutated genomic DNA
      can be identified in ovarian cystic fluid specimens. STUDY DESIGN: Forty-eight
      Japanese patients with cystic ovarian tumors (30 benign cysts, 8 borderline
      malignant tumors, and 10 cancers) were investigated. Cystic fluid and tumor
      tissue were obtained during surgery. After DNA extraction from the cystic fluid,
      polymerase chain reaction (PCR) and sequence analysis for exons 4-9 of the p53
      gene was performed. In two cases of mucinous cystic tumor of borderline
      malignancy and endometrioid adenocarcinoma, the p53 gene sequences were
      determined. Immunohistochemical staining for abnormal p53 gene product was also
      performed. RESULTS: DNA was successfully extracted from all cystic fluid
      specimens. Furthermore, exons 4-9 of the p53 gene could be identified by
      electrophoresis from all samples. In a mucinous cystic tumor of borderline
      malignancy, one point mutation was identified at codon 223 in exon 6 (CCT -> CTT)
      of the p53 gene. Aberrant p53 gene product was also observed in the tumor cells
      by immunohistochemical staining. Moreover, in another case of endometrial
      adenocarcinoma, a point mutation at codon 245 in exon 7 (GGC -> AGC) was detected
      by the direct sequencing of the amplified Exon. Notably, the mutation was not
      present in the peripheral blood (PB) sample and tissue specimens from the
      patient. CONCLUSION: In cystic ovarian tumors, cystic fluid may provide
      informative material for molecular studies since it reflects the p53 status of
      tumor tissue in the cyst wall. This system might help to identify ovarian
      malignancy without resection of the tumor tissues.

PMID- 24017962
TI  - Long-term follow-up after ureteral reimplantation in patients with severe deep
      infiltrating endometriosis.
AB  - OBJECTIVE: To investigate the intraoperative features and long-term postoperative
      results of patients with ureteral endometriosis who underwent ureteral
      reimplantation. STUDY DESIGN: In this retrospective study, we reviewed records of
      all patients with ureteral endometriosis treated by ureteral reimplantation. Pre
      , intra- and post-operative information was collected. RESULTS: Of patients
      operated for endometriosis, seven were diagnosed with severe ureteral
      endometriosis and underwent ureteral reimplantation. Psoas hitch was the
      preferred technique for the ureteral reimplantation. During a mean postoperative
      follow up of 42.3 +/- 20.0 months, all but one patient reported significant
      symptomatic improvement. None of the patients needed additional medical or
      surgical treatment and no recurrence was noted. CONCLUSION: Ureteral
      reimplantation performed by a multidisciplinary surgical team is a suitable
      technique in selected cases, gives good long-term results and has no need for
      repeated surgical treatment.

PMID- 24017963
TI  - Incidence of de novo stress incontinence after vaginal repair for pelvic organ
      prolapse.

PMID- 24017964
TI  - Good ideas are forever.

PMID- 24017965
TI  - Clinical reasoning and case-based decision making: the fundamental challenge to
      veterinary educators.
AB  - Confusion about the nature of human reasoning and its appropriate application to
      patients has hampered veterinary students' development of these skills. Expertise
      is associated with greater ability to deploy pattern recognition (type 1
      reasoning), which is aided by progressive development of data-driven, forward
      reasoning (in contrast to scientific, backward reasoning), analytical approaches
      that lead to schema acquisition. The associative nature of type 1 reasoning makes
      it prone to bias, particularly in the face of "cognitive miserliness," when clues
      that indicate the need for triangulation with an analytical approach are ignored.
      However, combined reasoning approaches, from the earliest stages, are more
      successful than one approach alone, so it is important that those involved in
      curricular design and delivery promote student understanding of reasoning
      generally, and the situations in which reasoning goes awry, and develop students'
      ability to reason safely and accurately whether presented with a familiar case or
      with a case that they have never seen before. 

PMID- 24017966
TI  - Diagnostic imaging learning resources evaluated by students and recent graduates.
AB  - Many learning resources can help students develop the problem-solving abilities
      and clinical skills required for diagnostic imaging. This study explored
      veterinary students' perceptions of the usefulness of a variety of learning
      resources. Perceived resource usefulness was measured for different levels of
      students and for academic versus clinical preparation. Third-year (n=139) and
      final (fifth) year (n=105) students and recent graduates (n=56) completed
      questionnaires on perceived usefulness of each resource. Resources were grouped
      for comparison: abstract/low complexity (e.g., notes, multimedia presentations),
      abstract/high complexity (e.g., Web-based and film case repositories),
      concrete/low complexity (e.g., large-group "clicker" workshops), and
      concrete/high complexity (e.g., small-group interpretation workshops). Lower
      level students considered abstract/low-complexity resources more useful for
      academic preparation and concrete resources more useful for clinical preparation.
      Higher-level students/recent graduates also considered abstract/low-complexity
      resources more useful for academic preparation. For all levels, lecture notes
      were considered highly useful. Multimedia slideshows were an interactive
      complement to notes. The usefulness of a Web-based case repository was limited by
      accessibility problems and difficulty. Traditional abstract/low-complexity
      resources were considered useful for more levels and contexts than expected.
      Concrete/high-complexity resources need to better represent clinical practice to
      be considered more useful for clinical preparation. 

PMID- 24017967
TI  - Synthesis and properties of Asante Calcium Red--a novel family of long excitation
      wavelength calcium indicators.
AB  - Although many synthetic calcium indicators are available, a search for compounds
      with improved characteristics continues. Here, we describe the synthesis and
      properties of Asante Calcium Red-1 (ACR-1) and its low affinity derivative (ACR-1
      LA) created by linking BAPTA to seminaphthofluorescein. The indicators combine a
      visible light (450-540 nm) excitation with deep-red fluorescence (640 nm). Upon
      Ca2+ binding, the indicators raise their fluorescence with longer excitation
      wavelengths producing higher responses. Although the changes occur without any
      spectral shifts, it is possible to ratio Ca(2+)-dependent (640 nm) and quasi
      independent (530 nm) emission when using visible (< 490 nm) or multiphoton (~780
      nm) excitation. Therefore, both probes can be used as single wavelength or, less
      dynamic, ratiometric indicators. Long indicator emission might allow easy [Ca2+]i
      measurement in GFP expressing cells. The indicators bind Ca2+ with either high
      (Kd = 0.49 +/- 0.07 MUM; ACR-1) or low affinity (Kd = 6.65 +/- 0.13 MUM; ACR-1
      LA). Chelating Zn2+ (Kd = 0.38 +/- 0.02 nM) or Mg2+ (Kd~5mM) slightly raises and
      binding Co2+ quenches dye fluorescence. New indicators are somewhat pH-sensitive
      (pKa = 6.31 +/- 0.07), but fairly resistant to bleaching. The probes are rather
      dim, which combined with low AM ester loading efficiency, might complicate in
      situ imaging. Despite potential drawbacks, ACR-1 and ACR-1-LA are promising new
      calcium indicators.

PMID- 24017968
TI  - Clinical correlations with Porphyromonas gingivalis antibody responses in
      patients with early rheumatoid arthritis.
AB  - INTRODUCTION: Prior studies have demonstrated an increased frequency of
      antibodies to Porphyromonas gingivalis (Pg), a leading agent of periodontal
      disease, in rheumatoid arthritis (RA) patients. However, these patients generally
      had long-standing disease, and clinical associations with these antibodies were
      inconsistent. Our goal was to examine Pg antibody responses and their clinical
      associations in patients with early RA prior to and after disease-modifying
      antirheumatic drug (DMARD) therapy. METHODS: Serum samples from 50 DMARD-naive RA
      patients were tested using an enzyme-linked immunosorbent assay with whole-Pg
      sonicate. For comparison, serum samples were tested from patients with late RA,
      patients with other connective tissue diseases (CTDs), age-similar healthy
      hospital personnel and blood bank donors. Pg antibody responses in early RA
      patients were correlated with standard RA biomarkers, measures of disease
      activity and function. RESULTS: At the time of enrollment, 17 (34%) of the 50
      patients with early RA had positive immunoglobulin G (IgG) antibody responses to
      Pg, as did 13 (30%) of the 43 patients with late RA. RA patients had
      significantly higher Pg antibody responses than healthy hospital personnel and
      blood bank donors (P < 0.0001). Additionally, RA patients tended to have higher
      Pg antibody reactivity than patients with other CTDs (P = 0.1), and CTD patients
      tended to have higher Pg responses than healthy participants (P = 0.07). Compared
      with Pg antibody-negative patients, early RA patients with positive Pg responses
      more often had anti-cyclic citrullinated peptide (anti-CCP) antibody reactivity,
      their anti-CCP levels were significantly higher (P = 0.03) and the levels of anti
      Pg antibodies correlated directly with anti-CCP levels (P < 0.01). Furthermore,
      at the time of study entry, the Pg-positive antibody group had greater rheumatoid
      factor values (P = 0.04) and higher inflammatory markers (erythrocyte
      sedimentation rate, or ESR) (P = 0.05), and they tended to have higher disease
      activity scores (Disease Activity Score based on 28-joint count (DAS28)-ESR and
      Clinical Disease Activity Index) and more functional impairment (Health
      Assessment Questionnaire). In Pg-positive patients, greater disease activity was
      still apparent after 12 months of DMARD therapy. CONCLUSIONS: A subset of early
      RA patients had positive Pg antibody responses. The responses correlated with
      anti-CCP antibody reactivity and to a lesser degree with ESR values. There was a
      trend toward greater disease activity in Pg-positive patients, and this trend
      remained after 12 months of DMARD therapy. These findings are consistent with a
      role for Pg in disease pathogenesis in a subset of RA patients.

PMID- 24017969
TI  - Evaluation of tracheal intubation: A retrospective study of skill acquisition by
      medical students in the operating theater.
AB  - BACKGROUND/PURPOSE: Tracheal intubation is a critical life-saving invasive
      procedure. Medical students generally obtain the skill of performing tracheal
      intubation in the operating theater during their anesthesiology rotation. In this
      study, we sought to characterize medical students' skill acquisition of tracheal
      intubation. METHODS: We retrospectively reviewed the logbooks of 94 medical
      students who had completed a 3-4 week rotation in our department between January
      2011 and June 2012. RESULTS: Ninety-four students performed 934 tracheal
      intubations. The success rate of intubation was 76.7%. After adjustment for age,
      body mass index, Mallampati class and grade, American Society of Anesthesiology
      (ASA) scores, and surgical category, the odds ratio of successful tracheal
      intubation improved with cumulative practice [odds ratio (OR) = 1.05 for each
      additional intubation performed; 95% confidence interval (CI) 1.00-1.09]. By
      contrast, the success rate decreased significantly with increasing scores of
      Mallampati class (OR = 0.32 for each increase in class; 95% CI 0.23-0.24) and
      grade (OR = 0.57 for each increase in grade; 95% CI 0.39-0.84). The main reason
      for intubation failure (57%) was poor visualization of vocal cords, due to
      suboptimal placement of the position of the laryngoscope. The satisfaction and
      confidence of students regarding the ability of performing tracheal intubation
      increased with each additional procedure, but decreased significantly after
      multiple unsuccessful attempts and the occurrence of any complication.
      CONCLUSION: Medical students acquired the ability of tracheal intubation and
      overcame major challenges through cumulative clinical practice of the procedure.

PMID- 24017970
TI  - The anticancer agent doxorubicin disrupts mitochondrial energy metabolism and
      redox balance in skeletal muscle.
AB  - The combined loss of muscle strength and constant fatigue are disabling symptoms
      for cancer patients undergoing chemotherapy. Doxorubicin, a standard chemotherapy
      drug used in the clinic, causes skeletal muscle dysfunction and premature fatigue
      along with an increase in reactive oxygen species (ROS). As mitochondria
      represent a primary source of oxidant generation in muscle, we hypothesized that
      doxorubicin could negatively affect mitochondria by inhibiting respiratory
      capacity, leading to an increase in H2O2-emitting potential. Here we demonstrate
      a biphasic response of skeletal muscle mitochondria to a single doxorubicin
      injection (20mg/kg). Initially at 2h doxorubicin inhibits both complex I- and II
      supported respiration and increases H2O2 emission, both of which are partially
      restored after 24h. The relationship between oxygen consumption and membrane
      potential (DeltaPsi) is shifted to the right at 24h, indicating elevated reducing
      pressure within the electron transport system (ETS). Respiratory capacity is
      further decreased at a later time point (72 h) along with H2O2-emitting potential
      and an increased sensitivity to mitochondrial permeability transition pore (mPTP)
      opening. These novel findings suggest a role for skeletal muscle mitochondria as
      a potential underlying cause of doxorubicin-induced muscle dysfunction.

PMID- 24017971
TI  - Dietary quercetin attenuates oxidant-induced endothelial dysfunction and
      atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: a critical
      role for heme oxygenase-1.
AB  - Several lines of evidence indicate that quercetin, a polyphenol derived in the
      diet from fruit and vegetables, contributes to cardiovascular health. We aimed to
      investigate the effects of dietary quercetin on endothelial function and
      atherosclerosis in mice fed a high-fat diet. Wild-type C57BL/6 (WT) and
      apolipoprotein E gene knockout (ApoE(-/-)) mice were fed: (i) a high-fat diet
      (HFD) or (ii) a HFD supplemented with 0.05% w/w quercetin (HFD+Q), for 14 weeks.
      Compared with animals fed HFD, HFD+Q attenuated atherosclerosis in ApoE(-/-)
      mice. Treatment with the HFD+Q significantly improved endothelium-dependent
      relaxation of aortic rings isolated from WT but not ApoE(-/-) mice and attenuated
      hypochlorous acid-induced endothelial dysfunction in aortic rings of both WT and
      ApoE(-/-) mice. Mechanistic studies revealed that HFD+Q significantly improved
      plasma F2-isoprostanes, 24h urinary nitrite, and endothelial nitric oxide
      synthase activity, and increased heme oxygenase-1 (HO-1) protein expression in
      the aortas of both WT and ApoE(-/-) mice (P<0.05). HFD+Q also resulted in small
      changes in plasma cholesterol (P<0.05 in WT) and plasma triacylglycerols (P<0.05
      in ApoE (-/-)mice). In a separate experiment, quercetin did not protect against
      hypochlorite-induced endothelial dysfunction in arteries obtained from
      heterozygous HO-1 gene knockout mice with low expression of HO-1 protein.
      Quercetin protects mice fed a HFD against oxidant-induced endothelial dysfunction
      and ApoE(-/-) mice against atherosclerosis. These effects are associated with
      improvements in nitric oxide bioavailability and are critically related to
      arterial induction of HO-1. 

PMID- 24017973
TI  - Phenotype of normal hairline maturation.
AB  - Hairlines change shape with age, starting at birth. A good head of hair is
      frequently present some time after ages 3 to 5 years. The look of childhood has
      its corresponding hairline, and, as the child grows and develops into adulthood,
      facial morphology migrate changes from a childlike look to a more mature look.
      This article discusses the dynamics of hairline evolution and the phenotypic
      variations of the front and side hairlines in men and women. A modeling system is
      introduced that provides a common language to define the various anatomic points
      of the full range of hairlines.

PMID- 24017972
TI  - Sulforaphane preconditioning of the Nrf2/HO-1 defense pathway protects the
      cerebral vasculature against blood-brain barrier disruption and neurological
      deficits in stroke.
AB  - Disruption of the blood-brain barrier (BBB) and cerebral edema are the major
      pathogenic mechanisms leading to neurological dysfunction and death after
      ischemic stroke. The brain protects itself against infarction via activation of
      endogenous antioxidant defense mechanisms, and we here report the first evidence
      that sulforaphane-mediated preactivation of nuclear factor erythroid 2-related
      factor 2 (Nrf2) and its downstream target heme oxygenase-1 (HO-1) in the cerebral
      vasculature protects the brain against stroke. To induce ischemic stroke, Sprague
      Dawley rats were subjected to 70 min middle cerebral artery occlusion (MCAo)
      followed by 4, 24, or 72 h reperfusion. Nrf2 and HO-1 protein expression was
      upregulated in cerebral microvessels of peri-infarct regions after 4-72 h, with
      HO-1 preferentially associated with perivascular astrocytes rather than the
      cerebrovascular endothelium. In naive rats, treatment with sulforaphane increased
      Nrf2 expression in cerebral microvessels after 24h. Upregulation of Nrf2 by
      sulforaphane treatment prior to transient MCAo (1h) was associated with increased
      HO-1 expression in perivascular astrocytes in peri-infarct regions and cerebral
      endothelium in the infarct core. BBB disruption, lesion progression, as analyzed
      by MRI, and neurological deficits were reduced by sulforaphane pretreatment. As
      sulforaphane pretreatment led to a moderate increase in peroxynitrite generation,
      we suggest that hormetic preconditioning underlies sulforaphane-mediated
      protection against stroke. In conclusion, we propose that pharmacological or
      dietary interventions aimed to precondition the brain via activation of the Nrf2
      defense pathway in the cerebral microvasculature provide a novel therapeutic
      approach for preventing BBB breakdown and neurological dysfunction in stroke.

PMID- 24017974
TI  - Imposters of androgenetic alopecia: diagnostic pearls for the hair restoration
      surgeon.
AB  - It is crucial that hair restoration surgeons understand the basic clinical
      diagnosis and pathologic condition of other hair loss conditions that are not
      always amenable to successful hair transplantation. In this article nonscarring
      and scarring mimickers of androgenetic alopecia are discussed. Nonscarring
      conditions include alopecia areata, telogen effluvium, and tinea capitis. Some of
      the more common scarring alopecias include lichen planopilaris, frontal fibrosing
      alopecia, and central centrifugal cicatricial alopecia. Less common inflammatory
      conditions include pseudopelade of Brocq, discoid lupus erythematosus, and
      folliculitis decalvans.

PMID- 24017975
TI  - Nonsurgical therapy for hair loss.
AB  - This article is an update of the currently available options for medical
      therapies to treat androgenetic alopecia in men and women. Emerging novel
      therapeutic modalities with potential for treating these patients are discussed.
      Because androgenetic alopecia is progressive in nature, stabilization of the
      process using medical therapy is an important adjunct to any surgical hair
      restoration plan. 

PMID- 24017976
TI  - Patient selection, candidacy, and treatment planning for hair restoration
      surgery.
AB  - Patient consultation, examination, and selection are crucial for successful
      outcomes in hair restoration surgery. The hair restoration surgeon must take a
      holistic approach in identifying those patients who are and who are not
      candidates for surgery. In this article, an overview of the consultation,
      pertinent physical examination features relating to patient candidacy, and
      several treatment paradigms are discussed. Additionally, those findings that may
      lead to poor results and conditions that are contraindications to hair
      restoration surgery are reviewed. 

PMID- 24017977
TI  - Hairline design and frontal hairline restoration.
AB  - Creating a natural hairline is one of the most important elements of a successful
      hair transplant. This article discusses the key skills needed to design a natural
      hairline. These are locating borders of the hairline as well as understanding and
      being able to mimic the visual characteristics of a hairline. Methods to locate
      the major borders and how to adjust them based on donor/recipient ratio are
      discussed. The visual characteristics of different hairline zones are described
      as well as techniques to recreate these characteristics using follicular unit
      grafting.

PMID- 24017978
TI  - Graft harvesting and management of the donor site.
AB  - The strip technique remains the most popular method of harvesting grafts. The
      challenge in every patient is to maximize the number of grafts while minimizing
      the scar. Fortunately, there are many ways to ensure that the donor site will be
      inconspicuous. This article reviews the details of planning for follicle graft
      harvesting, including formulae for assessing scalp laxity and calculating strip
      dimensions. The procedure is discussed in detail, from preparation of the donor
      site and estimation of graft total through closure of the incision. The author
      presents his preferences for the technique with rationale and surgical tips. 

PMID- 24017979
TI  - Follicular unit extraction.
AB  - The purpose of this article is to introduce the reader to the topic of follicular
      unit extraction (FUE) and to present an overview of the value of FUE to patients
      and physicians. In addition to this, the various methods and instrumentation for
      performing this method of graft harvest are discussed as well as some of the
      technique's inherent advantages and disadvantages. Topics unique to FUE,
      including body hair grafting, plug/minigrafts repair, and donor area management
      are addressed as well.

PMID- 24017980
TI  - Management of advanced hair loss patterns.
AB  - This article covers how to manage patients with extensive hair loss in whom
      complete, dense coverage is not possible. In addition to discussing planning a
      transplant pattern for already bald men, I discuss a conservative approach for
      recognizing and transplanting younger patients who have telltale warning signs
      that may evolve to extensive hair loss. For both groups, a variant of a frontal
      forelock-type pattern is usually the best course to follow. 

PMID- 24017981
TI  - Management of the crown.
AB  - Treatment of alopecia of the crown possesses several unique challenges for hair
      restoration physicians. In this article, the distinctive anatomic features and
      specific management paradigms related to the crown are discussed. This review
      also offers details on which surgical technique to implement for obtaining the
      most natural result possible that also yields the best possible apparent density.

PMID- 24017982
TI  - Female hair restoration.
AB  - Female hair loss is a devastating issue for women that has only relatively
      recently been publicly acknowledged as a significant problem. Hair transplant
      surgery is extremely successful in correcting the most cosmetically problematic
      areas of alopecia. This article discusses the surgical technique of hair
      transplantation in women in detail, including pearls to reduce postoperative
      sequelae and planning strategies to ensure a high degree of patient satisfaction.
      A brief overview of some of the medical treatments found to be helpful in slowing
      or reversing female pattern hair loss is included, addressing the available
      hormonal and topical treatments. 

PMID- 24017983
TI  - Megasessions: surgical indications and technical perspectives.
AB  - Surgical hair restoration allows male and female patients to achieve
      aesthetically natural results. The term megasession refers to transplanting
      greater then 3000 follicular unit grafts in a single procedure. By transplanting
      a large number of grafts, megasessions are capable of definitively treating a
      significant area of the scalp in 1 session. Patients must be carefully selected
      to determine whether they are appropriate candidates for an extended procedure.
      An experienced and well-organized surgical team is mandatory to meet the demands
      of this technically challenging and lengthy procedure. This article reviews the
      indications, contraindications, and technical perspectives surrounding
      megasession hair transplantation. 

PMID- 24017984
TI  - Dense packing: surgical indications and technical considerations.
AB  - Dense packing is the philosophy of fitting more than 30 to 35 follicular unit
      grafts per square centimeter in one operation. The aim is to produce a more even,
      consistent, and natural looking flow of hair after just one procedure. Although
      desirable in principle, not all patients are suitable candidates nor is it
      possible to achieve in certain patients (eg, coarse or curly hair). Patients who
      have sufficient donor availability, reasonably stable hair loss, and high hair-to
      skin color ratios are the ideal candidates. The authors highlight their
      philosophies and strategies for dense packing. 

PMID- 24017985
TI  - An analysis of follicular punches, mechanics, and dynamics in follicular unit
      extraction.
AB  - Success in follicular unit extraction requires an understanding of forces, fluid
      dynamics, instrumentation, and individual patient variation. Sharp punches
      require a lower axial and tangential force to dissect follicular groups. The
      angle of hair emergence and the size of a punch influence the wound size and the
      depth of an incision. A procedure must be individualized based on surface
      follicular group characteristics; hair splay; and strength of attachment between
      the outer root sheath, inner root sheath, and adipose with regard to hair
      follicles. 

PMID- 24017986
TI  - Optimal graft growth.
AB  - Excellent surgical results and high patient satisfaction with hair
      transplantation depend on attaining optimal growth. Unfortunately, even
      experienced surgeons acknowledge that graft survival often is not as high as is
      commonly stated. Hair transplant surgeons should be thoroughly familiar with the
      many variables that affect graft survival and refine their surgical techniques
      accordingly. This article provides a brief overview of the key factors that most
      significantly influence graft survival, including graft trauma,
      vascular/oxygenation factors, and biochemical injury. 

PMID- 24017987
TI  - Facial hair restoration: hair transplantation to eyebrows, beard, sideburns, and
      eyelashes.
AB  - Refinements in hair transplantation techniques allow the experienced surgeon to
      create natural-appearing facial hair transplants. Restoring eyebrows,
      beards/goatees, and sideburns have all become popular procedures, and the results
      can be outstanding. This article provides a comprehensive review of hair grafting
      techniques to achieve the best results in restoring various hair-bearing areas of
      the face, including the eyebrows, beard/goatee, and sideburns, and repairing the
      alopecic scarring from prior facial plastic surgery.

PMID- 24017988
TI  - Use of body hair and beard hair in hair restoration.
AB  - For many hair restoration patients with limited scalp donor hair it is possible
      to use nonhead hair sources to increase the potential follicle supply. Follicular
      unit extraction provides the hair restoration surgeon with a useful surgical
      means for accessing this valuable source of donor reserve. Nonhead hair can also
      be used to restore eyebrows, eyelashes, and moustaches. This article focuses on
      the use of body hair and beard in hair restoration. Discussed are the indications
      and effective techniques for performing hair transplants using non head hair
      donor sources, along with the pitfalls and risks of this surgical modality. 

PMID- 24017989
TI  - Hairline lowering.
AB  - Hairline lowering or advancement, also known as forehead reduction, is a
      procedure that has been adapted and honed from scalp reduction and flap
      techniques. Although the high hairline can be found in both men and women of all
      races and ethnicities due to various diagnoses, hairline advancement is best
      suited for individuals, typically women, with a lifelong history of a high
      hairline and no familial or personal history of progressive hair loss. It is a
      procedure that is both effective and efficient in lowering the congenitally high
      hairline with very high patient satisfaction. 

PMID- 24017990
TI  - Scalp repair using tissue expanders.
AB  - Repair of scalp defects is often challenging, because without careful planning,
      excision of the defect may leave unsatisfactory cosmesis. Contemporary techniques
      in hair restoration surgery allow creation of natural and undetectable results,
      but these techniques are often unsuitable for repairing large scarred areas of
      hair loss. However, by using older techniques of scalp reduction and tissue
      expansion, excision of many large scarring defects can be accomplished. Combining
      older methods with modern hair restoration surgery permits the satisfactory
      treatment of many previously untreatable conditions. This article focuses on
      tissue expansion as an adjunct to repairing large scalp defects. 

PMID- 24017991
TI  - Scalp micropigmentation: a useful treatment for hair loss.
AB  - Scalp micropigmentation (SMP) is a highly sophisticated medical tattoo process
      for balding or thinning hair. SMP looks amazingly simple, but this novel
      technique must be customized for each patient because the skin in each patient
      differs with regard to how the scalp reacts as it holds on to the tattoo dye.
      There are many variables involved with performing SMP that makes this process
      more of an art form than a science. SMP is a very labor-intensive process that
      could require multiple sessions and up to 20 hours of procedural time to satisfy
      the patient. This review discusses applications and technical considerations of
      the SMP process. 

PMID- 24017992
TI  - Complications in hair-restoration surgery.
AB  - Most complications associated with hair restoration are completely preventable
      and arise from variables that are directly controlled by the surgeon and the
      patient. Physicians who thoroughly grasp the nuances of modern surgical
      techniques and fully understand the physiologic dynamics of the balding process
      are least likely to generate a physician-controlled error. Highly motivated, well
      educated patients who carefully follow instructions and take an active role in
      the postoperative recovery process minimize the chance of patient-controlled
      errors. This article discusses potential complications associated with surgical
      hair restoration, and the roles of the patient and physician in minimizing the
      risk of complications. 

PMID- 24017993
TI  - Future horizons in hair restoration.
AB  - This article reviews the history of hair follicle regeneration from follicular
      fragments and dissociated cells. The challenges of trichogenic in vitro culture
      and subsequent delivery into the patient are discussed, as well as cosmetic
      acceptance, recent achievements on regeneration of human hair follicles, and new
      potential cell sources for hair regeneration.

PMID- 24017994
TI  - Hair restoration: a sophisticated art form.

PMID- 24017995
TI  - Functional signature of recovering cortex: dissociation of local field potentials
      and spiking activity in somatosensory cortices of spinal cord injured monkeys.
AB  - After disruption of dorsal column afferents at high cervical spinal levels in
      adult monkeys, somatosensory cortical neurons recover responsiveness to tactile
      stimulation of the hand; this reactivation correlates with a recovery of hand
      use. However, it is not known if all neuronal response properties recover, and
      whether different cortical areas recover in a similar manner. To address this, we
      recorded neuronal activity in cortical area 3b and S2 in adult squirrel monkeys
      weeks after unilateral lesion of the dorsal columns. We found that in response to
      vibrotactile stimulation, local field potentials remained robust at all frequency
      ranges. However, neuronal spiking activity failed to follow at high frequencies
      (>=15 Hz). We suggest that the failure to generate spiking activity at high
      stimulus frequency reflects a changed balance of inhibition and excitation in
      both area 3b and S2, and that this mismatch in spiking and local field potential
      is a signature of an early phase of recovering cortex (<two months).

PMID- 24017996
TI  - Neurotrophic factors rescue basal forebrain cholinergic neurons and improve
      performance on a spatial learning test.
AB  - This study investigated whether animals sustaining experimental damage to the
      basal forebrain cholinergic system would benefit from treatment with exogenous
      neurotrophic factors. Specifically, we set out to determine whether neurotrophic
      factors would rescue damaged cholinergic neurons and improve behavioral
      performance on a spatial learning and memory task. Adult rats received bilateral
      injections of either saline (controls) or 192 IgG-saporin to damage basal
      forebrain cholinergic neurons (BFCNs). Two weeks later, animals received implants
      of an Alzet mini-pump connected to cannulae implanted bilaterally in the lateral
      ventricles. Animals received infusions of nerve growth factor (NGF), neurotrophin
      3 (NT3), a combination of NGF and NT3, or a saline control over a 4-week period.
      Compared to saline-treated controls, animals sustaining saporin-induced damage to
      BFCNs took significantly more trials to learn a delayed match to position task
      and also performed more poorly on subsequent tests, with increasing delays
      between test runs. In contrast, animals infused with neurotrophins after saporin
      treatment performed significantly better than animals receiving saline infusions;
      no differences were detected for performance scores among animals infused with
      NGF, NT3, or a combination of NGF and NT3. Studies of ChAT immunnocytochemical
      labeling of BFCNs revealed a reduction in the numbers of ChAT-positive neurons in
      septum, nucleus of diagonal band, and nucleus basalis in animals treated with
      saporin followed by saline infusions, whereas animals treated with infusions of
      NGF, NT3 or a combination of NGF and NT3 showed only modest reductions in ChAT
      positive neurons. Together, these data support the notion that administration of
      neurotrophic factors can rescue basal forebrain cholinergic neurons and improve
      learning and memory performance in rats.

PMID- 24017997
TI  - An unusual case of Crohn's disease presenting with leg hematoma and arthritis.

PMID- 24017998
TI  - An uncommon pancreatic mass in a child and its clinical implications.

PMID- 24017999
TI  - Metal and nutrient dynamics on an aged intensive green roof.
AB  - Runoff and rainfall quality was compared between an aged intensive green roof and
      an adjacent conventional roof surface. Nutrient concentrations in the runoff were
      generally below Environmental Quality Standard (EQS) values and the green roof
      exhibited NO3(-) retention. Cu, Pb and Zn concentrations were in excess of EQS
      values for the protection of surface water. Green roof runoff was also
      significantly higher in Fe and Pb than on the bare roof and in rainfall. Input
      output fluxes revealed the green roof to be a potential source of Pb. High
      concentrations of Pb within the green roof soil and bare roof dusts provide a
      potential source of Pb in runoff. The origin of the Pb is likely from historic
      urban atmospheric deposition. Aged green roofs may therefore act as a source of
      legacy metal pollution. This needs to be considered when constructing green roofs
      with the aim of improving pollution remediation.

PMID- 24018000
TI  - Political drive to screen for pre-dementia: not evidence based and ignores the
      harms of diagnosis.

PMID- 24018001
TI  - Infant feeding practices and children's weight status.
AB  - PURPOSE: Feeding practices for young Canadian children from economically
      disadvantaged neighbourhoods were examined to determine adherence to infant
      feeding recommendations and factors associated with children's weight status.
      METHODS: Data for the study were collected from 1996 to 2003 as part of Better
      Beginnings, Better Futures, a longitudinal primary prevention initiative in
      Ontario. Study subjects were 546 children at age three months and 483 children at
      age 48 months. RESULTS: Mothers who had less than a high school education (odds
      ratio [OR] = 1.83, confidence interval [CI] = 1.01-3.29) and mothers who did not
      attend prenatal classes (OR = 2.37, CI = 1.33-4.24) were more likely to use
      formula. Mothers who were single parents were three times more likely to have an
      obese child (OR = 3.35, CI = 1.39-8.06) than were mothers who were married or
      with a partner. CONCLUSIONS: Targeted strategies are needed for families as
      single-parent households were predictive of obesity in young children. Innovative
      encouragement to participate in prenatal programming for pregnant women who have
      less than a high school education may improve breastfeeding rates.

PMID- 24018002
TI  - Fruit and vegetable consumption among children in a socioeconomically
      disadvantaged neighbourhood.
AB  - PURPOSE: Fruit and vegetable (FV) consumption was examined among children aged
      seven to 10 years in a London, Ontario, neighbourhood. The goal was to determine
      areas requiring targeted programs to promote healthy lifestyles. METHODS: Data
      were gathered from 136 students in grades 2 to 4. Each student attended one of
      four elementary schools within a neighbourhood designated a priority by the City
      of London Child and Youth Network. The Day in the Life Questionnaire was used to
      collect the data. Instances of FV consumption were compared with Eating Well with
      Canada's Food Guide (CFG) guidelines. RESULTS: Ninety-eight percent of
      participants did not follow the CFG-recommended minimum guidelines; they had
      fewer than five instances of FV consumption daily. Eighty-seven percent had fewer
      than two instances of FV consumption daily. CONCLUSIONS: These data support
      national findings of low FV consumption among children.

PMID- 24018003
TI  - [Relations between maternal food practices and diet of preschool age Quebec
      children].
AB  - PURPOSE: The goal of this study is to examine the relationships between mothers'
      food practices and the diets of their preschool children. METHODS: Daycare
      facilities on the Island of Montreal recruited 122 mothers to complete a self
      administered questionnaire that addressed the impact of parents' food practices
      on their children's diets, particularly the frequency of intake and food
      preferences. RESULTS: Correlations were observed between three maternal food
      practices--restrictions, pressure to eat and food reward--and children's eating
      behaviour. These three practices correlated with less desirable eating behaviours
      in children. CONCLUSIONS: This study suggests that in Quebec, mothers' food
      practices have a direct impact on the food practices of their children. Mothers
      must therefore be informed about the counterproductive nature of some food
      practices and given tools to develop healthier food strategies by focusing on
      children's appetites and emphasizing the pleasure of eating.

PMID- 24018004
TI  - Predicted and measured resting metabolic rate in young, non-obese women.
AB  - PURPOSE: Measured resting metabolic rate (RMR) was compared with predicted RMR in
      a sample of young, non-obese women. METHODS: In 52 women aged 19 to 30 with a
      body mass index of 16 to 29 kg/m2, RMR was measured with a MedGem indirect
      calorimeter and predicted with five commonly used equations: the Harris-Benedict
      (1919), Mifflin (1989), Owen (1985), Schofield (weight) (1985), and Schofield
      (weight and height) (1985) equations. Measured RMR and predicted RMR were
      compared through the use of various measures. RESULTS: In comparison with the
      measured RMR, the RMR predicted with four of the five equations was significantly
      higher (by 16 to 225 kcal/day, p < 0.001). At the group level, the Owen equation
      performed best and captured the greatest proportion of individuals (65%) for whom
      predicted RMR differed from measured RMR by less than 10%. With the other four
      equations, residuals exceeded 10% for more than two-thirds of participants. For
      the Harris-Benedict, Mifflin, and Owen equations, every 100 kcal/day increase in
      measured RMR was associated with a 6% to 8% decrease in error. The optimal
      prediction range (within 10% of the measured RMR) was different for each: Owen
      equation 1105 to 1400 kcal/day, Mifflin equation 1280 to 1595 kcal/day, and
      Harris-Benedict equation 1345 to 1630 kcal/day. CONCLUSIONS: Prediction equations
      should be modified according to the amount of corresponding percentage error.
      Where possible, RMR should be measured. Barring this, the Owen equation should be
      used for young, non-obese women.

PMID- 24018005
TI  - A study of challenges and opportunities for long-term care dietitians in British
      Columbia.
AB  - While demand for long-term care (LTC) in Canada is expected to grow in the coming
      years, little is known about the current LTC dietetic workforce or its members'
      practice-related concerns. A web-based survey was developed and distributed to
      and subsequently completed by 75 LTC dietitians in British Columbia. The survey
      was intended to characterize dietitians' demographic characteristics, educational
      and employment experiences, salaries and benefits, future employment plans, and
      concerns about current practice. Regression models were used to examine the
      associations between demographic, educational, and employment characteristics and
      self-reported hourly wages. The majority of respondents were employed at more
      than one facility (57%) and did not belong to a union (71%). The mean hourly wage
      for LTC dietetics positions was $37.50 +/- $5.85, and was significantly higher
      for positions that did not provide additional employee benefits (p < 0.05).
      Hourly wages were not significantly higher for dietitians with more years of
      experience or graduate-level education. Concerns were raised about potential
      implications of revised residential care regulations for workload, and only 36%
      of respondents reported being committed to working in the area of LTC dietetics
      in the future. This study highlights practice-related challenges and future
      opportunities to build the LTC dietetic workforce, and can inform planning for
      training, recruitment, and retention.

PMID- 24018006
TI  - Dietary patterns of female university students with nutrition education.
AB  - Dietary patterns were examined in a convenience sample of 36 female University of
      Alberta students, all of whom had completed at least one nutrition course. Data
      from a validated food frequency questionnaire were used to determine if students
      had a dietary pattern similar to that recommended in Eating Well with Canada's
      Food Guide (EWCFG) or by the Traditional Healthy Mediterranean Diet Pyramid
      (THMDP), as measured using a Mediterranean Diet Quality Index Score. No student
      consumed the THMDP minimum number of portions of legumes, seeds, and nuts, of
      olive oil, or of whole grains. The majority did not meet the minimum EWCFG
      recommendations for any food group. The results suggest that nutrition education
      alone may be insufficient to ensure optimal dietary patterns among female
      university students. The methodology reported in this study is novel in assessing
      whether dietary patterns resemble the THMDP or the EWCFG.

PMID- 24018007
TI  - An approach to improve parent participation in a childhood obesity prevention
      program.
AB  - PURPOSE: Engaging parents in interventions can be difficult because of various
      barriers. An engaging children's program that runs parallel to a parent program
      may facilitate parent participation. In this study, we assessed parents'
      perception of the children's component of Parents and Tots Together (PTT), a
      family-based obesity prevention program. METHODS: Fifteen of the 16 ethnically
      diverse parents who participated in an uncontrolled trial of PTT completed a
      survey assessing their satisfaction with the PTT children's component. More
      detailed information was obtained from one-on-one qualitative interviews with
      seven parents. RESULTS: Attendance at program sessions was relatively high; 69%
      of parents attended six or more of the nine sessions. Survey data revealed that
      87% of parents were "very satisfied" with the children's group. Approximately 73%
      of parents reported that the program was "very useful" in helping their child
      learn the importance of healthy eating and physical activity. In qualitative
      interviews, many parents identified the children's program as a motivator for
      attendance at the program sessions. CONCLUSIONS: The interactive children's
      program was well received by parents and may serve as a catalyst for parent
      participation. Larger, randomized trials are needed to determine the
      effectiveness of children's programming for enhancing parent participation.

PMID- 24018008
TI  - Cultivating an entrepreneurial mindset.
AB  - Now as never before, familiar challenges require bold, novel approaches.
      Registered dietitians will benefit by cultivating an entrepreneurial mindset that
      involves being comfortable with uncertainty, learning to take calculated risks,
      and daring to just try it. An entrepreneur is someone who takes risks to create
      something new, usually in business. But the entrepreneurial mindset is available
      to anyone prepared to rely only on their own abilities for their economic
      security and expect no opportunity without first creating value for others.

PMID- 24018009
TI  - Main issues in micronutrient supplementation in phenylketonuria.
AB  - For almost all patients with PKU, a low phenylalanine diet is the basis of the
      treatment despite a widely varying natural protein tolerance. A vitamin and
      mineral supplement is essential and it is commonly added to a phenylalanine-free
      (phe-free) source of L-amino acids. In PKU, many phe-free L-amino acid
      supplements have age-specific vitamin and mineral profiles to meet individual
      requirements. The main micronutrient sources are chemically derived and their
      delivery dosage is usually advised in three or more doses throughout the day.
      Within the EU, the composition of VM (vitamin and mineral) phe-free L-amino acid
      supplements is governed by the Foods for Special Medical Purposes (FSMP)
      directive (European Commission Directive number 1999/21/EC and amended by
      Directive 2006/141/EC). However the micronutrient composition of the majority
      fails to remain within FSMP micronutrient maximum limits per 100 kcal due to
      their low energy content and so compositional exceptions to the FSMP directive
      have to be granted for each supplement. All patients with PKU require an annual
      nutritional follow-up, until it has been proven that they are not at risk of any
      vitamin and mineral imbalances. When non-dietary treatments are used to either
      replace or act as an adjunct to diet therapy, the quality of micronutrient intake
      should still be considered important and monitored systematically. European
      guidelines are required about which micronutrients should be measured and the
      conditions (fasting status) for monitoring.

PMID- 24018010
TI  - Swedish hunters' safety behaviour and experience of firearm incidents.
AB  - Since any firearm injury is potentially lethal, it is of great interest to
      prevent firearm incidents. This study investigated such incidents during hunting
      and Swedish hunters' safety behaviour. A 48-item questionnaire was posted to a
      random sample of 1000 members of the Swedish Association for Hunting and Wildlife
      Management. The questions considered demographics, hunting experience/hunting
      habits/safety behaviour/attitudes and experience of careless weapon handling,
      hunters' weapons and safety behaviour relating to weapons, health status, firearm
      incidents and their preventability, and personal comments on the questionnaire.
      The response rate was almost 50%. The mean age of the responders was 54 years; 5%
      were females. Almost none (1%) reported hunting under the influence of alcohol.
      Young age and male sex were positively associated with risk behaviour, although
      the presence of multiple risk behaviours in the same responder was not common. A
      very high degree of compliance with Swedish laws regarding weapon storage was
      reported. One-quarter of the responders had witnessed a firearm incident caused
      by another hunter, which in most situations did not result in human injury or
      death. An unsafetied weapon was the most common reported "cause" of these
      incidents. Experience of a firearm incident was not uncommon and the majority of
      the responders considered the incident in question to be preventable. This study
      provides a picture of the possible risk behaviour among hunters and the results
      suggest that future prevention work should target safer weapon handling. 

PMID- 24018011
TI  - Transposition of the great arteries and cor triatriatum: a rare combination.
AB  - In this case report, we present a 5-month-old girl diagnosed with a unique
      combination of transposition of the great arteries and cor triatriatum sinistra.
      A 1-day-old female patient presented to our hospital with cyanosis since the
      early neonatal period. We confirmed transposition of the great arteries by
      echocardiography. The patient underwent arterial switch operation on day 8 and
      was discharged on day 35. After 5 months of the operation, the patient had a
      lower respiratory tract infection and was unable to gain weight. Echocardiography
      revealed mild neopulmonary regurgitation, minimal neoaortic regurgitation, and
      pulmonary arterial hypertension. In addition, a fibrous membrane was also seen
      dividing the left atrium. The patient was diagnosed with cor triatriatum and
      underwent successful resection of the membrane. 

PMID- 24018012
TI  - Communicating genetics and smoking through social media: are we there yet?
AB  - BACKGROUND: Social media is a recent source of health information that could
      disseminate new scientific research, such as the genetics of smoking. OBJECTIVE:
      The objectives were (1) to evaluate the availability of genetic information about
      smoking on different social media platforms (ie, YouTube, Facebook, and Twitter)
      and (2) to assess the type and the content of the information displayed on the
      social media as well as the profile of people publishing this information.
      METHODS: We screened posts on YouTube, Facebook, and Twitter with the terms
      "smoking" and "genetic" at two time points (September 18, 2012, and May 7, 2013).
      The first 100 posts were reviewed for each media for the time points. Google was
      searched during Time 2 as an indicator of available information on the Web and
      the other social media that discussed genetics and smoking. The source of
      information, the country of the publisher, characteristics of the posts, and
      content of the posts were extracted. RESULTS: On YouTube, Facebook, and Twitter,
      31, 0, and 84 posts, respectively, were included. Posts were mostly based on
      smoking-related diseases, referred to scientific publications, and were largely
      from the United States. From the Google search, most results were scientific
      databases. Six scientific publications referred to within the Google search were
      also retrieved on either YouTube or Twitter. CONCLUSIONS: Despite the importance
      of public understanding of smoking and genetics, and the high use of social
      media, little information on this topic is actually present on social media.
      Therefore, there is a need to monitor the information that is there and to
      evaluate the population's understanding of the information related to genetics
      and smoking that is displayed on social media.

PMID- 24018013
TI  - Striving to achieve safe, permanent treatment discontinuation in chronic myeloid
      leukemia.
AB  - Small clinical studies have found that patients with idealized response to
      imatinib can sustain long-lasting responses after treatment discontinuation,
      suggesting that these patients may be effectively "cured" of chronic myeloid
      leukemia (CML). Treatment discontinuation is not presently considered routine
      practice and is not recommended outside the context of clinical research. Many
      questions remain regarding "cure" in CML: how "cure" is defined, what factors
      predict successful treatment discontinuation, and what management strategies are
      the most appropriate post-discontinuation, especially when molecular relapse
      occurs. This review addresses these issues and discusses the current knowledge
      regarding treatment discontinuation and a potential for "cure" of CML. 

PMID- 24018014
TI  - Human recombinant arginase I(Co)-PEG5000 [HuArgI(Co)-PEG5000]-induced arginine
      depletion is selectively cytotoxic to human acute myeloid leukemia cells.
AB  - In this study, we target arginine auxotrophy of AML cell lines using human
      arginase I cobalt-PEG5000. HuArgI(Co)-PEG5000 was cytotoxic to all AML cell lines
      tested. Mononuclear cells and CD34(+) blasts were not sensitive demonstrating the
      selectivity of HuArgI(Co)-PEG5000-induced arginine deprivation. Addition of L
      citrulline led to the rescue of five cell lines. The four cell lines that were
      not rescued by L-citrulline did not express argininosuccinate synthetase-1,
      indicating complete arginine auxotrophy. Inhibition of autophagy increased cell
      sensitivity to HuArgI(Co)-PEG5000 demonstrating the protective role of autophagy
      following arginine deprivation. We have shown that AML can be selectively
      targeted using HuArgI(Co)-PEG5000-induced arginine depletion.

PMID- 24018015
TI  - Vaginal cyst in a newborn.

PMID- 24018016
TI  - The nutritional dilemma for preterm infants: how to promote neurocognitive
      development and linear growth, but reduce the risk of obesity.

PMID- 24018018
TI  - Vesicular self-assembly of colloidal amphiphiles in microfluidics.
AB  - Hydrodynamic flow in a microfluidic (MF) device offers a high-throughput platform
      for the continuous and controllable self-assembly of amphiphiles. However, the
      role of hydrodynamics on the assembly of colloidal amphiphiles (CAMs) is still
      not well understood. This Article reports a systematic study of the assembly of
      CAMs, which consist of Au nanoparticles (AuNPs) grafted with amphiphilic block
      copolymers, into vesicles with a monolayer of CAMs in the membranes using laminar
      flows in MF flow-focusing devices. Our experimental and simulation studies
      indicate that the transverse diffusion of solvents and colloids across the
      boundary of neighboring lamellar flows plays a critical role in the assembly of
      CAMs into vesicles. The dimension of the vesicles can be controlled in the range
      of 100-600 nm by tuning the hydrodynamic conditions of the flows. In addition,
      the diffusion coefficient of CAMs was also critical for their assembly. Under the
      same flow conditions, larger CAMs generated larger assemblies as a result of the
      reduced diffusion rate of large amphiphiles. This work could provide fundamental
      guidance for the preparation of nanoparticle vesicles with applications in
      bioimaging, drug delivery, and nano- and microreactors. 

PMID- 24018017
TI  - Preadmission metformin use and mortality among intensive care patients with
      diabetes: a cohort study.
AB  - INTRODUCTION: Metformin has anti-inflammatory and anti-thrombotic effects that
      may improve the outcome of critical illness, but clinical data are limited. We
      examined the impact of preadmission metformin use on mortality among intensive
      care unit (ICU) patients with type 2 diabetes. METHODS: We conducted this
      population-based cohort study among all persons admitted to the 17 ICUs in
      Northern Denmark (population approximately 1.8 million). We focused on all
      patients with type 2 diabetes who were admitted to the ICUs between January 2005
      and December 2011. Through individual-level linkage of population-based medical
      databases, type 2 diabetes was identified using a previously validated algorithm
      including hospital diagnoses, filled prescriptions for anti-diabetic drugs, and
      elevated HbA1c levels. Metformin use was identified by filled prescriptions
      within 90 days before admission. Covariates included surgery, preadmission
      morbidity, diabetes duration, and concurrent drug use. We computed 30-day
      mortality and hazard ratios (HRs) of death using Cox regression adjusted for
      covariates, both overall and after propensity score matching. RESULTS: We
      included 7,404 adult type 2 diabetes patients, representing 14.0% of 52,964 adult
      patients admitted to the ICUs. Among type 2 diabetes patients, 1,073 (14.5%)
      filled a prescription for metformin as monotherapy within 90 days before
      admission and 1,335 (18.0%) received metformin in combination with other anti
      diabetic drugs. Thirty-day mortality was 17.6% among metformin monotherapy users,
      17.9% among metformin combination therapy users, and 25.0% among metformin non
      users. The adjusted HRs were 0.80 (95% confidence interval (CI): 0.69, 0.94) for
      metformin monotherapy users and 0.83 (95% CI: 0.71, 0.95) for metformin
      combination therapy users, compared to non-users. Propensity-score-matched
      analyses yielded the same results. The association was evident across most
      subgroups of medical and surgical ICU patients, but most pronounced in elderly
      patients and in patients with well-controlled diabetes. Former metformin use was
      not associated with decreased mortality. CONCLUSIONS: Preadmission metformin use
      was associated with reduced 30-day mortality among medical and surgical intensive
      care patients with type 2 diabetes.

PMID- 24018019
TI  - Robotic and laparoscopic radical cystectomy for bladder cancer: long-term
      oncologic outcomes.
AB  - BACKGROUND: Extended oncologic outcomes after minimally invasive cystectomy have
      not been previously reported. OBJECTIVE: To report outcomes of robot-assisted
      radical cystectomy (RARC) and laparoscopic radical cystectomy (LRC) for bladder
      cancer (BCa) at up to 12-yr follow-up. DESIGN, SETTING, AND PARTICIPANTS: All 121
      patients undergoing RARC or LRC for BCa between December 1999 and September 2008
      at a tertiary referral center were retrospectively evaluated from a prospectively
      maintained database. INTERVENTION: RARC or LRC. OUTCOME MEASUREMENTS AND
      STATISTICAL ANALYSIS: Primary end points were overall survival (OS), cancer
      specific survival (CSS), and recurrence-free survival (RFS) calculated using
      Kaplan-Meier curves. Secondary end points were survival analysis by number of
      lymph nodes (LNs) and type of procedure. Surgical outcomes, including
      complications, were analyzed. RESULTS AND LIMITATIONS: Most tumors were muscle
      invasive (>= pT2; n=81; 67%) urothelial carcinomas (n=102; 84%). Extended LN
      dissection was performed in 98 patients (81%), with a median of 14 nodes removed
      (interquartile range [IQR]: 8-18). Twenty-four patients (20%) had node-positive
      disease (N1: 10 [8%]; N2: 14 [12%]). Eight patients (6.6%) had positive soft
      tissue margins. Median follow-up was 5.5 yr (mean: 5.9; IQR: 4.2-8.2; range: 0.13
      12.1). At last follow-up, 58 patients (48%) had no evidence of disease, 3 (2%)
      were alive with recurrence, 59 (49%) had died, and status was unknown in 1.
      Twenty-eight patients (23%) died from cancer-specific causes, 20 (17%) from
      unrelated causes, and 11 (9%) from unknown causes. The 10-yr actuarial OS, CSS,
      and RFS rates were 35%, 63%, and 54%, respectively. At last follow-up, OS for
      pT0, pTis/a, pT1, pT2, and pT3 versus pT4 was 67%, 73%, 53%, 50%, and 16% versus
      0%, respectively (p=0.02). At last follow-up, CSS for pT0, pTis/a, pT1, pT2, and
      pT3 versus pT4 was 100%, 91%, 74%, 77%, and 56% versus 0%, respectively (p=0.03).
      CONCLUSIONS: The longest oncologic outcomes following RARC and LRC for BCa
      reported demonstrates results similar to those reported for open RC. Continued
      analysis and direct randomized comparison between techniques is necessary.

PMID- 24018020
TI  - Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic
      review and meta-analysis of randomized trials.
AB  - CONTEXT: The role of adjuvant chemotherapy remains poorly defined for the
      management of muscle-invasive bladder cancer (MIBC). The last meta-analysis
      evaluating adjuvant chemotherapy, conducted in 2005, had limited power to fully
      support its use. OBJECTIVE: To update the current evidence of the benefit of
      postoperative adjuvant cisplatin-based chemotherapy compared with control (ie,
      surgery alone) in patients with MIBC. EVIDENCE ACQUISITION: A comprehensive
      literature review was performed to identify all randomized controlled trials
      (RCTs) comparing adjuvant cisplatin-based chemotherapy with control for patients
      with MIBC. The search included the Medline, Embase, Cochrane Central Register of
      Controlled Trials databases, and abstracts from the American Society of Clinical
      Oncology meetings up to May 2013. An updated systematic review and meta-analysis
      was performed. EVIDENCE SYNTHESIS: A total of 945 patients included in nine RCTs
      (five previously analyzed, one updated, and three new) were examined. For overall
      survival, the pooled hazard ratio (HR) across all nine trials was 0.77 (95%
      confidence interval [CI], 0.59-0.99; p=0.049). For disease-free survival, the
      pooled HR across seven trials reporting this outcome was 0.66 (95% CI, 0.45-0.91;
      p=0.014). This disease-free survival benefit was more apparent among those with
      positive nodal involvement (p=0.010). CONCLUSIONS: This updated and improved meta
      analysis of randomized trials provides further evidence of an overall survival
      and disease-free survival benefit in patients with MIBC receiving adjuvant
      cisplatin-based chemotherapy after radical cystectomy.

PMID- 24018021
TI  - Telomerase reverse transcriptase promoter mutations in bladder cancer: high
      frequency across stages, detection in urine, and lack of association with
      outcome.
AB  - BACKGROUND: Hotspot mutations in the promoter of the gene coding for telomerase
      reverse transcriptase (TERT) have been described and proposed to activate gene
      expression. OBJECTIVES: To investigate TERT mutation frequency, spectrum,
      association with expression and clinical outcome, and potential for detection of
      recurrences in urine in patients with urothelial bladder cancer (UBC). DESIGN,
      SETTING, AND PARTICIPANTS: A set of 111 UBCs of different stages was used to
      assess TERT promoter mutations by Sanger sequencing and TERT messenger RNA (mRNA)
      expression by reverse transcription-quantitative polymerase chain reaction. The
      two most frequent mutations were investigated, using a SNaPshot assay, in an
      independent set of 184 non-muscle-invasive and 173 muscle-invasive UBC (median
      follow-up: 53 mo and 21 mo, respectively). Voided urine from patients with
      suspicion of incident UBC (n=174), or under surveillance after diagnosis of non
      muscle-invasive UBC (n=194), was tested using a SNaPshot assay. OUTCOME
      MEASUREMENTS AND STATISTICAL ANALYSIS: Association of mutation status with age,
      sex, tobacco, stage, grade, fibroblast growth factor receptor 3 (FGFR3) mutation,
      progression-free survival, disease-specific survival, and overall survival.
      RESULTS AND LIMITATIONS: In the two series, 78 of 111 (70%) and 283 of 357 (79%)
      tumors harbored TERT mutations, C228T being the most frequent substitution (83%
      for both series). TERT mutations were not associated with clinical or pathologic
      parameters, but were more frequent among FGFR3 mutant tumors (p=0.0002). There
      was no association between TERT mutations and mRNA expression (p=0.3). Mutations
      were not associated with clinical outcome. In urine, TERT mutations had 90%
      specificity in subjects with hematuria but no bladder tumor, and 73% in
      recurrence-free UBC patients. The sensitivity was 62% in incident and 42% in
      recurrent UBC. A limitation of the study is its retrospective nature.
      CONCLUSIONS: Somatic TERT promoter mutations are an early, highly prevalent
      genetic event in UBC and are not associated with TERT mRNA levels or disease
      outcomes. A SNaPshot assay in urine may help to detect UBC recurrences.

PMID- 24018022
TI  - Intensity modulated radiotherapy for stage III non-small cell lung cancer in the
      United States: predictors of use and association with toxicities.
AB  - BACKGROUND: Intensity modulated radiotherapy for stage III lung cancer has become
      commonplace in the United States in the absence of randomized controlled trials.
      We used a large, population-based database to determine which factors led to
      increased utilization of IMRT and to evaluate associations of IMRT with
      toxicities. METHODS: The Surveillance, Epidemiology, and End Results (SEER)
      Medicare records identified 3986 individuals aged 66 years or older diagnosed
      with stage III lung cancer between 2001 and 2007 and treated with IMRT or 3D
      conformal radiotherapy. Predictors of IMRT use were determined using logistic
      regression. Associations of IMRT use with diagnosis codes for radiation-related
      toxicities were evaluated with multivariate proportional hazards regression and
      propensity-score matching. RESULTS: Among the 3986 patients studied, the median
      age was 75 years, 54.1% were male, and 62% had IIIA disease. Two hundred and
      fifty seven (6.5%) patients received IMRT, with use increasing from 0.5% in 2001
      to 14.7% in 2007 (P < 0.001). Key predictors of IMRT delivery included increasing
      year of diagnosis and treatment in a freestanding center (odds ratio, 2.10; 95%
      confidence interval [CI], 1.59-2.77, P < 0.001); tumor size, stage, and number of
      radiotherapy fractions delivered were not associated with IMRT use. IMRT use was
      not associated with a higher burden of lung or esophagus toxicities when compared
      to 3DCRT. CONCLUSION: These findings suggest that practice environment strongly
      influenced adoption of IMRT for lung cancer. Patient and tumor factors were not
      significant predictors of IMRT use. Esophagus and lung toxicity rates were
      similar between IMRT and 3DCRT.

PMID- 24018023
TI  - A retrospective analysis of 335 Japanese lung cancer patients who responded to
      initial gefitinib treatment.
AB  - BACKGROUND: Gefitinib treatment results in considerably better progression-free
      survival compared with that of platinum doublets in the first line treatment of
      nonsmall-cell lung cancer (NSCLC) carrying an activating epidermal growth factor
      receptor (EGFR) mutation. Some patients who respond to gefitinib have an overall
      survival (OS) of more than 5 years, whereas other initial responders do less
      well. Although there has been considerable effort made to elucidate the
      mechanisms of acquired resistance, there have only been a few studies that
      addressed the effect of clinical backgrounds and treatment histories on the
      survival of the patients who had responded to an EGFR-tyrosine kinase inhibitor
      (TKI). In this study, we especially focused on the clinical benefit of EGFR-TKI
      administration after progression. PATIENTS AND METHODS: We retrospectively
      analyzed consecutive patients with advanced NSCLC who were diagnosed before
      October 2010, treated with gefitinib after July 2002, and responded to it. The
      primary objective of this study was to evaluate how clinical backgrounds and
      treatment histories influence survival of the patients who respond to gefitinib.
      The secondary objectives were to evaluate the safety of long-term gefitinib use
      and to establish the optimal treatment sequence using a dynamic treatment regimen
      analysis (DTRA). RESULTS: A total of 335 patients were recruited. Twenty-eight
      (8.4%) patients survived more than 5 years. Sixty-five and 93 patients received
      gefitinib as rechallenge and beyond progressive disease (BPD), respectively. A
      statistically significant difference in OS was observed between the patients who
      underwent gefitinib rechallenge and those who did not rechallenge (median: 1272
      days vs. 774 days; p < 0.001), a result supported by a DTRA. Patients treated
      with gefitinib BPD also showed a tendency of longer survival. CONCLUSIONS:
      Gefitinib rechallenge and BPD played a central role in long term survival of the
      patients who initially responded to gefitinib.

PMID- 24018024
TI  - Imaging in pleural mesothelioma: a review of the 11th International Conference of
      the International Mesothelioma Interest Group.
AB  - Imaging of malignant pleural mesothelioma (MPM) is essential to the diagnosis,
      assessment, and monitoring of this disease. The complex morphology and growth
      pattern of MPM, however, create unique challenges for image acquisition and
      interpretation. These challenges have captured the attention of investigators
      around the world, some of whom presented their work at the 2012 International
      Conference of the International Mesothelioma Interest Group (iMig 2012) in
      Boston, Massachusetts, USA, September 2012. The measurement of tumor thickness on
      computed tomography (CT) scans is the current standard of care in the assessment
      of MPM tumor response to therapy; in this context, variability among observers in
      the measurement task and in the tumor response classification categories derived
      from such measurements was reported. Alternate CT-based tumor response criteria,
      specifically direct measurement of tumor volume change and change in lung volume
      as a surrogate for tumor response, were presented. Dynamic contrast-enhanced CT
      has a role in other settings, but investigation into its potential use for
      imaging mesothelioma tumor perfusion only recently has been initiated. Magnetic
      resonance imaging (MRI) and positron-emission tomography (PET) are important
      imaging modalities in MPM and complement the information provided by CT. The
      pointillism sign in diffusion-weighted MRI was reported as a potential parameter
      for the classification of pleural lesions as benign or malignant, and PET
      parameters that measure tumor activity and functional tumor volume were presented
      as indicators of patient prognosis. Also reported was the use of PET/CT in the
      management of patients who undergo high-dose radiation therapy. Imaging for MPM
      impacts everything from initial patient diagnosis to the outcomes of clinical
      trials; iMig 2012 captured this broad range of imaging applications as
      investigators exploit technology and implement multidisciplinary approaches
      toward the benefit of MPM patients. 

PMID- 24018025
TI  - Identification of subgroup patients with stage IIIB/IV non-small cell lung cancer
      at higher risk for brain metastases.
AB  - PURPOSE: Brain metastases (BM), a common occurrence in non-small cell lung cancer
      (NSCLC), usually lead to a poor prognosis. Recently, the selection of treatment
      modalities for BM has modestly improved patient survival and quality of life.
      Treatment choice is largely based on the number of BM, the presence of BM-related
      symptoms, and performance status. Therefore, early BM detection is crucial. In
      this study, we aimed to elucidate the factors associated with BM and identify
      subgroups of patients at higher risk for BM. METHODS AND PATIENTS: The medical
      records of 596 consecutive patients with stage I-IV NSCLC were reviewed between
      January 2006 and November 2011. A multivariate logistic regression (MLR) model
      was used to identify factors associated with BM. RESULTS: Among 482 eligible
      stage IIIB/IV NSCLC patients, 173 (36%) experienced BM during their disease
      course. On MLR analysis, female gender, age < 60 years and adenocarcinoma were
      associated with BM (OR = 1.71, 95% CI = 1.06-2.75, P = 0.028; OR = 2.11, 95% CI =
      1.38-3.22, P = 0.001; and OR = 2.39, 95% CI = 1.16-4.92, P = 0.018,
      respectively). The actuarial incidence of BM varied widely from 14% to 59% in
      different subgroups; younger patients with adenocarcinoma tended to experience BM
      more than older patients with squamous cell carcinoma (OR = 6.88, 95% CI = 2.97
      15.94, P < 0.001). Furthermore, the incidence of BM correlated closely with
      survival after NSCLC diagnosis, and it was 42%, 54% and 64% in patients who
      survived more than 3, 12 and 24 months, respectively. Notably, the number of BM,
      the size of the largest BM and the proportion of multiple BM, defined as more
      than 4 metastatic tumors in brain, were significantly different in NSCLC patients
      with and without BM-related symptoms or signs (4.0 +/- 2.1 vs 2.7 +/- 1.9, P <
      0.001; 2.6 +/- 1.5 vs 1.3 +/- 1.0 CM, P < 0.001, and 50% vs 21%, P < 0.001,
      respectively). CONCLUSION: We found that subgroups of NSCLC patients
      characterized by younger age, female gender and adenocarcinoma are at higher
      risks for BM. These findings might be helpful to detect BM earlier and facilitate
      the design of clinical trials aiming at their prevention.

PMID- 24018026
TI  - Clinical approach to dermatologic disease in exotic animals.
AB  - Skin disease is an extremely common presenting complaint to the exotic animal
      practitioner. A systematic diagnostic approach is necessary in these cases to
      achieve a diagnosis and formulate an effective treatment plan. In all exotic
      species, husbandry plays a central role in the pathogenesis of cutaneous disease,
      so a thorough evaluation of the husbandry is critical for successful management.
      The clinical approach to skin disease in exotic animal patients is reviewed with
      specific focus on structure and function of the skin, diagnostic testing, and
      differential diagnoses for commonly encountered cutaneous diseases. 

PMID- 24018027
TI  - Cutaneous neoplasia in ferrets, rabbits, and guinea pigs.
AB  - The frequency of common cutaneous tumors in ferrets, rabbits, and guinea pigs is
      summarized, with descriptions of their appearance and behavior, prognosis, and
      treatment options. This information assists clinicians when talking to clients,
      and helps owners make an informed decision whether or not to pursue aggressive
      treatment or to palliate. 

PMID- 24018028
TI  - Erythema multiforme in a ferret (Mustela putorius furo).
AB  - Erythema multiforme, an uncommon skin disease resulting from an aberrant immune
      response, was diagnosed in a domestic ferret (Mustela putorius furo) based on
      clinical signs and skin biopsies, and this seems to be the first case report of
      this dermal disease in the ferret. This article discusses treatment and response,
      and reviews the small animal literature as it relates to disease pathophysiology
      and treatment. 

PMID- 24018029
TI  - Ectoparasites in small exotic mammals.
AB  - Ectoparasites inhabiting the skin are responsible for significant problems in
      small mammals, owing to ingestion of blood, lymph, sebaceous secretions, and
      scavenging skin debris, as well as a hypersensitivity reaction to parasite
      antigen resulting in severe pruritus and subsequent self-trauma-induced lesions.
      In general practice, the most common diagnosis in exotic pets is an unspecified
      mite infestation, but other ectoparasites such as lice, fleas, insects, or even
      helminths may cause dermatologic diseases. If treatment with topical insecticides
      is planned, the small mammal should be isolated for a few hours to enable drying
      and spreading of the product. 

PMID- 24018030
TI  - Chrysosporium anamorph Nannizziopsis vriesii: an emerging fungal pathogen of
      captive and wild reptiles.
AB  - Chrysosporium anamorph Nannizziopsis vriesii is a recent pathogen associated with
      infections in lizards, snakes, and crocodilians. It seems to be an obligate
      pathogen. It has been isolated from wild reptiles in addition to captive animals.
      Affected animals often present with aggressive, pyogranulomatous lesions that can
      affect the integument and musculoskeletal systems. Diagnosis can be done using
      culture, histopathology, and polymerase chain reaction assay. Ancillary
      diagnostic tests can be useful in characterizing the health status of the
      affected reptile and aid in planning supportive care and therapy. Treatment using
      antifungals has shown mixed results. 

PMID- 24018031
TI  - Pathogenesis, diagnosis, and treatment of amphibian chytridiomycosis.
AB  - Chytridiomycosis, caused by the chytridiomycete fungus, Batrachochytrium
      dendrobatidis, is an important pathogen of amphibians in captivity and is a major
      concern for global conservation of amphibians. The organism infects keratinized
      epithelial cells of amphibian skin and causes disease and mortality by
      interfering with important skin functions, especially electrolyte balance.
      Primary treatments are with antifungal medications applied in a topical bath
      solution, and itraconazole is the most commonly used agent, although several
      different options are available. Supportive treatment of the clinically ill
      patient is necessary for success, with particular attention to electrolyte
      therapy. 

PMID- 24018032
TI  - Itchy fish and viral dermatopathies: sampling, diagnosis, and management of
      common viral diseases.
AB  - Viral dermatopathies of fish bear clinical signs similar to those of
      dermatopathies from other causes. This article offers an overview to approaching
      dermatologic presentations in fish, with an emphasis on sampling, diagnosis, and
      management of viral dermatopathies, building on previous publications. It is
      vital to recognize clinical signs associated with viral dermatopathies because
      there are currently no treatments available. Avoidance and prevention is the key
      to controlling viral diseases in fish. Optimizing husbandry practices and
      providing appropriate quarantine procedures can help prevent viral disease
      outbreaks in collection and aquaculture stocks. 

PMID- 24018033
TI  - Viral skin diseases of the rabbit.
AB  - This article describes the viral skin diseases affecting the domestic rabbit, the
      most important being myxomatosis. Transmission and pathogenesis, clinical signs,
      diagnosis, treatment, and control are described and the article will be of
      interest to veterinary practitioners who treat rabbits. Shope fibroma virus,
      Shope papilloma virus, and rabbitpox are also discussed. 

PMID- 24018034
TI  - Bumblefoot: a comparison of clinical presentation and treatment of pododermatitis
      in rabbits, rodents, and birds.
AB  - Pododermatitis, also known as bumblefoot, is a common condition encountered in
      birds, rabbits, and rodents in clinical practice. This article compares the
      anatomy and physiology of the foot and the predisposing factors for
      pododermatitis in each of the species discussed. Clinical presentation,
      diagnostics, and treatment options, including medical and surgical therapies, are
      provided. In addition, alternative therapies, including natural remedies,
      therapeutic laser, and acupuncture, are explored. This article is intended to
      encourage practitioners to use a multimodal approach for successful management of
      this disease in all species. 

PMID- 24018035
TI  - Vesicular, ulcerative, and necrotic dermatitis of reptiles.
AB  - Vesicular, ulcerative, and necrotic dermatologic conditions are common in captive
      reptiles. Although these conditions have distinct differences histologically,
      they are commonly sequelae to each other. This article examines the anatomy and
      physiology of reptile skin; discusses reported causes of vesicular, ulcerative,
      and necrotic dermatologic conditions; and reviews various management options. 

PMID- 24018036
TI  - Ovarian cysts in the guinea pig (Cavia porcellus).
AB  - This article reviews ovarian cysts in the guinea pig (Cavia porcellus), a disease
      commonly associated with symmetric, nonpruritic alopecia of the dorsum and
      flanks. Relevant anatomy is discussed and current theories of pathogenesis are
      reviewed. Prevalence, predisposing factors, diagnosis, treatment, and prognosis
      are presented. 

PMID- 24018037
TI  - Dermatological conditions affecting the beak, claws, and feet of captive avian
      species.
AB  - Captive avian species are presented for veterinary care for a variety of
      conditions and clinical signs. Although many of these presented birds seek
      veterinary care for other causes, some of these presentations involve
      dermatologic conditions that involve the beak, claws, and feet. A variety of
      presentations commonly seen include trauma to the beak, claws, and/or feet; leg
      band injuries, pododermatitis, infectious causes, and beak growth abnormalities.
      Other less common presentations include thermal burns to the feet, self
      mutilation of the feet, tumors of the feet and claws, and avian gout. 

PMID- 24018038
TI  - Behavioral dermatopathies in small mammals.
AB  - Several skin conditions seen in small mammals are thought to have a behavioral
      cause but their epidemiology and pathogenesis are poorly understood. A
      significant amount of research exists on barbering in mice that suggests it is an
      impulse control disorder and may represent a good animal model for
      trichotillomania in humans. Stress seems to play a complex role in the
      development and maintenance of some behavioral dermatopathies, but genetics and
      experiences, especially during development, also likely play a role. Pain or
      discomfort may underlie the development of many of these problems. 

PMID- 24018039
TI  - Select topics in dermatology.

PMID- 24018040
TI  - Cardiac arrest caused by acute intoxication-insight from a registry.
AB  - INTRODUCTION: The aim of the study was to evaluate the epidemiology and outcome
      after cardiac arrest caused by intoxication. METHODS: A retrospective analysis of
      1991 to 2010 medical record of patients experiencing cardiac arrest caused by
      self-inflicted, intentional intoxication was performed. The setting was an
      emergency department of a tertiary care university hospital. The primary end
      point was the presentation of epidemiologic data in relation to favorable
      neurologic outcome, defined as cerebral performance categories 1 or 2 and 180-day
      survival. Furthermore, the patients were subdivided into a single-substance and
      polysubstance group, depending on the substances causing the intoxication.
      RESULTS: Of 3644 patients admitted to our department, 99 (2.7%) with a median age
      of 26 (interquartile range, 19-42) years (37% female) were included. Cardiac
      arrest was witnessed in 62 cases (63%). Eleven patients (11%) received basic life
      support by bystanders, and 11 (11%) had a shockable rhythm in the initial
      electrocardiogram. The combined end point "good survival" was achieved by 34
      patients (34%). Cardiac arrest occurred out of hospital in 73 patients (74%) and
      in-hospital in 26 patients (26%). A single substance causing the intoxication was
      found in 56 patients (56%). Opiates were the leading substance, with 25 patients
      (25%) using them. CONCLUSION: Cardiac arrest caused by intoxication is found
      predominately in young patients. Overall, favorable neurologic survival was
      achieved in 34%. Opiate-related cardiac arrest was associated with poor survival
      and a high incidence of neurologic deficits.

PMID- 24018041
TI  - IL-22 activates oxidant signaling in pulmonary vascular smooth muscle cells.
AB  - Reactive oxygen species (ROS) mediate cell-signaling processes in response to
      various ligands and play important roles in the pathogenesis of cardiovascular
      diseases. The present study reports that interleukin-22 (IL-22) elicits signal
      transduction in vascular smooth muscle cells (SMCs) through a ROS-dependent
      mechanism. We find that pulmonary artery SMCs express IL-22 receptor alpha 1 and
      that IL-22 activates STAT3 through this receptor. IL-22-induced signaling is
      found to be mediated by NADPH oxidase, as indicated by the observations that the
      inhibition and siRNA knock-down of this enzyme inhibit IL-22 signaling. IL-22
      triggers the oxidative modifications of proteins through protein carbonylation
      and protein glutathionylation. Mass spectrometry identified some proteins that
      are carbonylated in response to IL-22 stimulation, including alpha-enolase, heat
      shock cognate 71kDa protein, mitochondrial 60kDa heat shock protein, and
      cytoplasmic 2 actin and determined that alpha-tubulin is glutathionylated.
      Protein glutathionylation and STAT3 phosphorylation are enhanced by the siRNA
      knock-down of glutaredoxin, while IL-22-mediated STAT3 phosphorylation is
      suppressed by knocking down thioredoxin interacting protein, an inhibitor of
      thioredoxin. IL-22 is also found to promote the growth of SMCs via NADPH oxidase.
      In rats, pulmonary hypertension is found to be associated with increased smooth
      muscle IL-22 expression. These results show that IL-22 promotes the growth of
      pulmonary vascular SMCs via a signaling mechanism that involves NADPH oxidase
      dependent oxidation. 

PMID- 24018042
TI  - Two non-coding RNAs, MicroRNA-101 and HOTTIP contribute cartilage integrity by
      epigenetic and homeotic regulation of integrin-alpha1.
AB  - Non-coding RNAs have been less studied in cartilage development and destruction
      regulated by sophisticated molecular events despite their considerable
      theranostic potential. In this study, we identified significant down-regulation
      of mR-101 and up-regulation of lncRNA, HOTTIP in the processes of endochondral
      ossification and osteoarthritic progression. In wing mesenchymal cells, up
      expression of miR-101 by TGF-beta3 treatment is targeting DNMT-3B and thereby
      altered the methylation of integrin-alpha1 addressed as a positive regulator of
      endochondral ossification in this study. In like manner, down-regulation of miR
      101 also coordinately up-regulated DNMT-3B, down-regulated integrin-alpha1, and
      resulted in cartilage destruction. In an OA animal model, introduction of
      lentiviruses that encoded miR-101 or integrin-alpha1 successfully reduced
      cartilage destruction. In like manner, long non-coding RNA (lncRNA), HOTTIP, a
      known regulator for HoxA genes, was highly up-regulated and concurrent down
      regulation of HoxA13 displayed the suppression of integrin-alpha1 in OA
      chondrocytes. In conclusion, two non-coding RNAs, miR-101 and HOTTIP regulate
      cartilage development and destruction by modulating integrin-alpha1 either
      epigenetically by DNMT-3B or transcriptionally by HoxA13 and data further suggest
      that these non-coding RNAs could be a potent predictive biomarker for OA as well
      as a therapeutic target for preventing cartilage-related diseases. 

PMID- 24018043
TI  - Crystal structure of Src-like adaptor protein 2 reveals close association of SH3
      and SH2 domains through beta-sheet formation.
AB  - The Src-like adaptor proteins (SLAP/SLAP2) are key components of Cbl-dependent
      downregulation of antigen receptor, cytokine receptor, and receptor tyrosine
      kinase signaling in hematopoietic cells. SLAP and SLAP2 consist of adjacent SH3
      and SH2 domains that are most similar in sequence to Src family kinases (SFKs).
      Notably, the SH3-SH2 connector sequence is significantly shorter in SLAP/SLAP2
      than in SFKs. To understand the structural implication of a short SH3-SH2
      connector sequence, we solved the crystal structure of a protein encompassing the
      SH3 domain, SH3-SH2 connector, and SH2 domain of SLAP2 (SLAP2-32). While both
      domains adopt typical folds, the short SH3-SH2 connector places them in close
      association. Strand betae of the SH3 domain interacts with strand betaA of the
      SH2 domain, resulting in the formation of a continuous beta sheet that spans the
      length of the protein. Disruption of the SH3/SH2 interface through mutagenesis
      decreases SLAP-32 stability in vitro, consistent with inter-domain binding being
      an important component of SLAP2 structure and function. The canonical peptide
      binding pockets of the SH3 and SH2 domains are fully accessible, in contrast to
      other protein structures that display direct interaction between SH3 and SH2
      domains, in which either peptide binding surface is obstructed by the
      interaction. Our results reveal potential sites of novel interaction for SH3 and
      SH2 domains, and illustrate the adaptability of SH2 and SH3 domains in mediating
      interactions. As well, our results suggest that the SH3 and SH2 domains of SLAP2
      function interdependently, with implications on their mode of substrate binding. 

PMID- 24018044
TI  - Activins bind and signal via bone morphogenetic protein receptor type II (BMPR2)
      in immortalized gonadotrope-like cells.
AB  - TGFbeta superfamily ligands greatly outnumber their receptors. Thus, receptors
      are shared between ligands and individual ligands can bind multiple receptors.
      Bone morphogenetic proteins (BMPs) bind and signal via both BMP type II (BMPR2)
      and activin type II (ACVR2) receptors. We hypothesized that, in addition to its
      canonical receptor ACVR2, activin A might similarly bind and signal via BMPR2.
      First, using surface plasmon resonance, we showed that activin A binds to the
      BMPR2 extracellular domain (ECD), though with lower affinity compared to the
      ACVR2-ECD. We confirmed these results in cells, where radiolabeled activin A
      bound to ACVR2 and BMPR2, but not to other type II receptors (AMHR2 or TGFBR2).
      Using homology modeling and site-directed mutagenesis, we identified key residues
      in BMPR2 that mediate its interaction with activin A. The soluble ECDs of ACVR2
      or BMPR2 dose-dependently inhibited activin A-, but not TGFbeta-induced signaling
      in cells, suggesting that activin binding to BMPR2 could have functional
      consequences. To address this idea, we altered BMPR2 expression levels in
      immortalized murine gonadotrope-like cells, LbetaT2, in which activins potently
      stimulate follicle-stimulating hormone beta (Fshb) subunit transcription. BMPR2
      expression potentiated activin A responses whereas depletion of endogenous BMPR2
      with short interfering RNAs attenuated activin A-stimulated Fshb transcription.
      Additional data suggest, for the first time, that BMPR2 may form functional
      complexes with the canonical activin type I receptor, activin receptor-like
      kinase 4. Collectively, our data show that BMPR2, along with ACVR2, functions as
      a bona fide activin type II receptor in gonadotrope-like cells, thereby
      broadening our understanding of mechanisms of activin action. 

PMID- 24018045
TI  - G protein-coupled receptor kinase 2 (GRK2) is a Rho-activated scaffold protein
      for the ERK MAP kinase cascade.
AB  - The G protein-coupled receptor kinases (GRKs) are best known for their role in
      phosphorylating and desensitising G protein-coupled receptors (GPCRs). The GRKs
      also regulate signalling downstream of other families of receptors and have a
      number of non-receptor substrates and binding partners. Here we identify RhoAGTP
      and Raf1 as novel binding partners of GRK2 and report a previously unsuspected
      function for this kinase. GRK2 is a RhoA effector that serves as a RhoA-activated
      scaffold protein for the ERK MAP kinase cascade. The ability of GRK2 to bind to
      Raf1, MEK1 and ERK2 is dependent on RhoAGTP binding to the catalytic domain of
      the kinase. Exogenous GRK2 has previously been shown to increase ERK activation
      downstream of the epidermal growth factor receptor (EGFR). Here we find that GRK2
      mediated ERK activation downstream of the EGFR is Rho-dependent and that
      treatment with EGF promotes RhoAGTP binding and ERK scaffolding by GRK2.
      Depletion of GRK2 expression by RNAi reveals that GRK2 is required for EGF
      induced, Rho- and ERK-dependent thymidine incorporation in vascular smooth muscle
      cells (VSMCs). We therefore hypothesise that Rho-dependent ERK MAPK scaffolding
      by GRK2 downstream of the EGFR may have an important role in the vasculature,
      where increased levels of both GRK2 and RhoA have been associated with
      hypertension. 

PMID- 24018046
TI  - Hexokinase 1 blocks apoptotic signals at the mitochondria.
AB  - To coordinate a meaningful response to infection or tissue damage, Tumor Necrosis
      Factor (TNF) triggers a spectrum of reactions in target cells that includes cell
      activation, differentiation, proliferation and death. Deregulated TNF signaling
      can lead to tissue damage and organ dysfunction during inflammation. Previously,
      we identified hexokinase 1 (HK1) as a potent pro-survival factor that counters
      TNF-induced apoptosis in type II cells. Here we used HK1 siRNA and clotrimazole
      to generate mitochondrial depletion phenotypes of HK1 to test if HK1 acts at the
      mitochondria to block TNF-induced apoptosis. We found that HK1 is predominantly
      mitochondrial in type II cells and that its depletion at the mitochondria
      decreased the inner mitochondrial membrane potential and accelerated TNF-induced
      apoptosis. In addition, we showed that the decrease of the mitochondrial membrane
      potential after HK1 depletion depended on the presence of Bak and Bax and was
      blocked by Bcl-2 overexpression. From these findings, we conclude that HK1
      counters TNF-induced apoptosis through antagonization of pro-apoptotic Bcl-2
      proteins at the outer mitochondrial membrane. 

PMID- 24018047
TI  - MicroRNA-dependent cross-talk between VEGF and HIF1alpha in the diabetic retina.
AB  - Both HIF1alpha (hypoxia-inducible factor alpha) and VEGF (vascular endothelial
      growth factor) are implicated in the pathogenesis of diabetic retinopathy (DR).
      Competitive endogenous RNAs (ceRNAs) are messenger RNA (mRNA) molecules that
      affect each other expression through competition for their shared microRNAs
      (miRNA). However, little is known about the role of ceRNAs in DR. We assess
      whether the expression of HIF1alpha and VEGF in DR is interdependent through
      sequestration of common miRNAs. We used bioinformatics to identify potential
      miRNAs that affect both genes and validated the interdependence of the genes by
      silencing or overexpression of the genes and assessed the luciferase-HIF1alpha
      3'UTR activity. We found that HIF1alpha and VEGF are targeted by 12 common
      miRNAs. Silencing either HIF1alpha or VEGF increased the availabilities of the
      shared miRNAs, therefore suppressed the luciferase-HIF1alpha 3'UTR activity,
      whereas over-expressing HIF1alpha or VEGF increased the luciferase activity.
      HIF1alpha was co-expressed with VEGF in-vivo and in-vitro in DR models. Silencing
      HIF1alpha transcripts resulted in a significant reduction in VEGF protein levels
      and vice versa. This interdependence was miRNA- and 3'UTR-dependent, as silencing
      Dicer abolished the interdependence. Over-expression of a common miRNA (miR-106a)
      significantly reduced the expression of HIF1alpha and VEGF and prevented high
      glucose-induced increased permeability. There is a cross-talk between HIF1alpha
      and VEGF through interactions with their common miRNAs. miRNA based therapy can
      affect the expression of both HIF1alpha and VEGF and may represent a therapeutic
      potential for the treatment of DR. 

PMID- 24018048
TI  - Structural basis of calcineurin activation by calmodulin.
AB  - Calcineurin is the only known calmodulin (CaM) activated protein phosphatase,
      which is involved in the regulation of numerous cellular and developmental
      processes and in calcium-dependent signal transduction. Although commonly assumed
      that CaM displaces the autoinhibitory domain (AID) blocking substrate access to
      its active site, the structural basis underlying activation remains elusive. We
      have created a fused ternary complex (CBA) by covalently linking three
      polypeptides: CaM, calcineurin regulatory B subunit (CnB) and calcineurin
      catalytic A subunit (CnA). CBA catalytic activity is comparable to that of fully
      activated native calcineurin in the presence of CaM. The crystal structure showed
      virtually no structural change in the active site and no evidence of CaM despite
      being covalently linked. The asymmetric unit contains four molecules; two
      parallel CBA pairs are packed in an antiparallel mode and the large cavities in
      crystal packing near the calcineurin active site would easily accommodate
      multiple positions of AID-bound CaM. Intriguingly, the conformation of the
      ordered segment of AID is not altered by CaM; thus, it is the disordered part of
      AID, which resumes a regular alpha-helical conformation upon binding to CaM,
      which is displaced by CaM for activation. We propose that the structural basis of
      calcineurin activation by CaM is through displacement of the disordered fragment
      of AID which otherwise impedes active site access. 

PMID- 24018050
TI  - RIO kinase 3 acts as a SUFU-dependent positive regulator of Hedgehog signaling.
AB  - Suppressor of fused (SUFU) is an essential negative regulator of the mammalian
      Hedgehog (HH) signaling pathway and its loss is associated with cancer
      development. On a cellular level, endogenous SUFU can mainly be detected in the
      cytoplasm and the nucleus. However, immunostaining of pancreatic cancer specimen
      revealed the existence of cell types showing selective enrichment of endogenous
      SUFU in the nucleus. Following up on this observation, we found that a SUFU
      construct which was experimentally tethered exclusively to the nucleus was unable
      to antagonize endogenous HH signaling, in contrast to control SUFU. These data
      suggest that alterations in the normal subcellular distribution of SUFU might
      interfere with its established negative role on the HH pathway. Performing a
      multi-well kinase screen in human cells identified RIO kinase 3 (RIOK3) as a
      novel modulator of SUFU subcellular distribution. Functionally, RIOK3 acts as a
      SUFU-dependent positive regulator of HH signaling. Taken together, we propose
      that factors modulating the nucleo-cytoplasmic distribution of SUFU impact on the
      normal function of this tumor suppressing protein. 

PMID- 24018049
TI  - Regulated in DNA damage and development 1 (REDD1) promotes cell survival during
      serum deprivation by sustaining repression of signaling through the mechanistic
      target of rapamycin in complex 1 (mTORC1).
AB  - Regulated in DNA damage and development 1 (REDD1) functions to repress signaling
      through the mechanistic target of rapamycin (mTOR) protein kinase in complex 1
      (mTORC1) in response to diverse stress conditions. In the present study, we
      investigated the role of REDD1 in the response of cells to growth cessation
      induced by serum deprivation. REDD1 expression was induced within 2h of depriving
      cells of serum, with the induction being mediated through ER stress, as evidenced
      by activation of PERK, enhanced eIF2alpha phosphorylation, and ATF4 facilitated
      transcription of the REDD1 gene. In wild-type cells, signaling through mTORC1 was
      rapidly (within 30min) repressed in response to serum deprivation and the
      repression was sustained for at least 10h. In contrast, in REDD1 knockout cells
      mTORC1 signaling recovered toward the end of the 10h-deprivation period.
      Interestingly, Akt phosphorylation initially declined in response to serum
      deprivation and then recovered between 2 and 4h in wild-type but not REDD1
      knockout cells. The recovery of mTORC1 signaling and the failure of Akt
      phosphorylation to do so in the REDD1 knockout cells were accompanied by a
      dramatic increase in caspase-3 cleavage and cell death, both of which were
      blocked by rapamycin. Furthermore, overexpression of constitutively active Akt
      rescued REDD1 knockout cells from serum deprivation induced cell death. Overall,
      the results implicate REDD1 as a key regulatory checkpoint that coordinates
      growth signaling inputs to activate pro-survival mechanisms and reduce
      susceptibility to cell death. 

PMID- 24018051
TI  - MiR-27a modulates the MDR1/P-glycoprotein expression by inhibiting FZD7/beta
      catenin pathway in hepatocellular carcinoma cells.
AB  - Chemotherapy has been widely used to treat cancer, however, the appearance of
      multiple drug resistance (MDR) in cancer patients is regarded as a major clinical
      obstacle to successful chemotherapy. MicroRNAs (miRNAs) are evolutionary
      conserved small RNAs that regulate gene expression at the post-transcriptional
      level and have been shown to regulate cell differentiation, development,
      proliferation and apoptosis. Nevertheless, the involvement of miRNAs and their
      roles in the development of MDR in liver cancer are not fully understood. Our
      study found that the expression of miR-27a was down-regulated in the multidrug
      resistant hepatocellular carcinoma cell line BEL-7402/5-fluorouracil (BEL/5-FU)
      compared with its parental BEL-7402 cell line, while the MDR1/P-glycoprotein
      expression was elevated. Overexpression of miR-27a by transfecting with miR-27a
      mimics in the BEL/5-FU cells could reduce the MDR1/P-glycoprotein and beta
      catenin expressions, enhance the sensitivity of these cells to 5-fluorouracil and
      5-fluorouracil-induced apoptosis. Moreover, up-regulation of miR-27a did not
      decrease the FZD7 mRNA level, but significantly reduce its protein expression in
      BEL/5-FU cells. It was also confirmed that reduction of FZD7 by RNA interference
      induced inhibitory effects on the expression of MDR1/P-glycoprotein and beta
      catenin, similar to miR-27a. Taken together, our findings suggest that miR-27a
      could function as a novel regulator to reverse MDR in hepatocellular carcinoma
      cells by inhibiting the FZD7/beta-catenin pathway. 

PMID- 24018052
TI  - Therapeutic potential of fecal microbiota transplantation.
AB  - There has been growing interest in the use of fecal microbiota for the treatment
      of patients with chronic gastrointestinal infections and inflammatory bowel
      diseases. Lately, there has also been interest in its therapeutic potential for
      cardiometabolic, autoimmune, and other extraintestinal conditions that were not
      previously considered to be associated with the intestinal microbiota. Although
      it is not clear if changes in the microbiota cause these conditions, we review
      the most current and best methods for performing fecal microbiota transplantation
      and summarize clinical observations that have implicated the intestinal
      microbiota in various diseases. We also discuss case reports of fecal microbiota
      transplantations for different disorders, including Clostridium difficile
      infection, irritable bowel syndrome, inflammatory bowel diseases, insulin
      resistance, multiple sclerosis, and idiopathic thrombocytopenic purpura. There
      has been increasing focus on the interaction between the intestinal microbiome,
      obesity, and cardiometabolic diseases, and we explore these relationships and the
      potential roles of different microbial strains. We might someday be able to mine
      for intestinal bacterial strains that can be used in the diagnosis or treatment
      of these diseases. 

PMID- 24018053
TI  - Incidental diagnosis of a familial left ventricular noncompaction on a chest CT
      angiography.

PMID- 24018054
TI  - Health professionals' views on Indigenous Health and the delivery of healthcare
      services in the Pilbara.
AB  - PURPOSE: To explore health professionals' views about Australian Indigenous
      people's health and the delivery of healthcare to them in the Pilbara region of
      Western Australia. METHODS: An open-ended questionnaire was used to gather
      information from health professionals located across diverse regions in the
      Pilbara. The responses were analysed with the use of thematic analysis. In the
      first stage, codes were developed by assigning names to small sections of the
      interview transcripts. Next, the most salient incisive codes were identified and
      developed into themes that captured the most important issues. FINDINGS: Twenty
      eight health professionals indicated that the most important health issues were
      chronic diseases, substance abuse and ear disease. These health issues were often
      attributed to a cycle of poor health perpetuated throughout generations.
      Educational initiatives were thought to be integral to intervening in this cycle.
      Of particular importance in improving the effectiveness of educational
      initiatives was facilitating the participation of Australian Indigenous peoples
      to determine the content of such initiatives. The other main issues the health
      professionals identified were lifting the standard of Australian Indigenous
      housing and implementing strategies to improve the continuity of healthcare.
      CONCLUSION: Educational initiatives need to be prioritised to improve the health
      of Australian Indigenous people in the Pilbara and the initiatives should be
      delivered with the involvement of the local community in order to increase the
      likelihood of sustained behavioural change. Innovative solutions are required to
      improve the continuity of healthcare in the Pilbara, including increased use of
      mobile services.

PMID- 24018056
TI  - Melanoma follow up: time to generate the evidence.
AB  - Research is needed into current melanoma follow-up practices and their
      implications for patients and society. We highlight the need and suggest a way
      forward. 

PMID- 24018055
TI  - A cost analysis of inpatient compared with outpatient prostaglandin E2 cervical
      priming for induction of labour: results from the OPRA trial.
AB  - OBJECTIVE: To compare the costs of inpatient (usual care) with outpatient
      (intervention) care for cervical priming for induction of labour in women with
      healthy, low-risk pregnancies who are being induced for prolonged pregnancies or
      for social reasons. METHODS: Data from a randomised controlled trial at two
      hospitals in South Australia were matched with hospital financial data. A cost
      analysis comparing women randomised to inpatient care with those randomised to
      outpatient care was performed, with an additional analysis focusing on those who
      received the intervention. RESULTS: Overall, 48% of women randomised into the
      trial did not receive the intervention. Women randomised to outpatient care had
      an overall cost saving of $319 per woman (95% CI -$104 to $742) as compared with
      women randomised to usual care. When restricted to women who actually received
      the intervention, in-hospital cost savings of $433 (95% CI -$282 to $1148) were
      demonstrated in the outpatient group. However, these savings were partially
      offset by the cost of an outpatient priming clinic, reducing the overall cost
      savings to $156 per woman. CONCLUSIONS: Overall cost savings were not
      statistically significant in women who were randomised to or received the
      intervention. However, the trend in cost savings favoured outpatient priming.

PMID- 24018057
TI  - Profiling bone and joint problems and health service use in an Australian
      regional population: the Port Lincoln Health Study.
AB  - OBJECTIVES: To describe the burden of bone and joint problems (BJP) in a defined
      regional population, and to identify characteristics and service-usage patterns.
      METHODS: In 2010, a health census of adults aged >=15 years was conducted in Port
      Lincoln, South Australia. A follow-up computer-assisted telephone interview
      provided more specific information about those with BJP. RESULTS: Overall, 3350
      people (42%) reported current BJP. General practitioners (GP) were the most
      commonly used provider (85%). People with BJP were also 85% more likely to visit
      chiropractors, twice as likely to visit physiotherapists and 34% more likely to
      visit Accident and Emergency or GP out of hours (compared with the rest of the
      population). Among the phenotypes, those with BJP with co-morbidities were more
      likely to visit GP, had a significantly higher mean pain score and higher levels
      of depression or anxiety compared with those with BJP only. Those with BJP only
      were more likely to visit physiotherapists. CONCLUSIONS: GP were significant
      providers for those with co-morbidities, the group who also reported higher
      levels of pain and mental distress. GP have a central role in effectively
      managing this phenotype within the BJP population including linking allied health
      professionals with general practice to manage BJP more efficiently.

PMID- 24018058
TI  - Self-management activities in diabetes care: a systematic review.
AB  - OBJECTIVE: To identify the range of self-management activities people diagnosed
      with diabetes engage in to manage their disease, the frequency of use, and
      whether self-management practices change over time. METHODS: A systematic review
      of the literature was undertaken. Thirty-two studies identified through
      electronic databases met the inclusion criteria and were included in the review.
      RESULTS: The study found that people living with diabetes undertake regular self
      management activities and that compliance with medication regimes is high.
      Adherence, however, varied with respect to blood glucose testing, diet, physical
      activity and foot care. Levels of physical activity were not found to change over
      time. Evidence suggests that some people with diabetes modify their self
      management practices in response to factors such as holidays. CONCLUSIONS: The
      review suggests that the majority of people with diabetes self-manage, although
      there is variation in adherence to key self-management activities. How self
      management practices change over time and whether this impacts on health outcomes
      is an area for future research.

PMID- 24018059
TI  - Development of a Translation Standard to support the improvement of health
      literacy and provide consistent high-quality information.
AB  - Australia has a high number of people from culturally and linguistically diverse
      (CALD) backgrounds whose primary language is not English. CALD population groups
      have comparatively lower levels of education and health literacy, and poorer
      health outcomes compared with the Australian-born population. The delivery of
      consumer health information to people from CALD backgrounds usually includes the
      use of translated resources. Unfortunately, the quality of translated resources
      available on health issues is highly variable and may impact efforts to address
      the disparities in health outcomes. Currently applied guides to translation focus
      on accuracy and literalness of the translation; however, for health translations,
      conveying meaning and incorporating culturally relevant information is essential.
      Minimum standards for developing translated resources are needed to provide an
      indication of quality for end users, including healthcare providers, the client
      and carer. This paper describes the development of a Translation Standard, led by
      a community nursing organisation in collaboration and consultation with CALD
      community members and peak community organisations in Melbourne, Australia. The
      Translation Standard includes 10 components that have been identified as
      necessary to ensure a minimum standard of translation that is of high quality and
      caters to the health literacy levels of the target audience. 

PMID- 24018060
TI  - Attitudes and beliefs of staff to feedback following the review of adverse events
      in clinical care.
AB  - OBJECTIVE: To undertake a pilot project to determine how clinical and non
      clinical staff perceive feedback given to them following clinical incident
      reviews. METHODS: An online survey was devised and sent as a link to staff across
      the Murrumbidgee Local Health District who would be likely to submit patient
      related adverse incidents into the NSW Health Incident Information Management
      System. RESULTS: Two hundred and twenty-eight responses were received. Feedback
      was viewed as constructive and helpful. Medical staff were less enthusiastic
      about feedback and preferred formal feedback processes. CONCLUSIONS: Feedback
      from clinical incident reviews closes the loop of the review process and creates
      a platform for necessary changes to be undertaken.

PMID- 24018063
TI  - Cardiomyocyte-secreted acetylcholine is required for maintenance of homeostasis
      in the heart.
AB  - Heart activity and long-term function are regulated by the sympathetic and
      parasympathetic branches of the nervous system. Parasympathetic neurons have
      received increased attention recently because acetylcholine (ACh) has been shown
      to play protective roles in heart disease. However, parasympathetic innervation
      is sparse in the heart, raising the question of how cholinergic signaling
      regulates cardiomyocytes. We hypothesized that non-neuronal secretion of ACh from
      cardiomyocytes plays a role in cholinergic regulation of cardiac activity. To
      test this possibility, we eliminated secretion of ACh exclusively from
      cardiomyocytes by targeting the vesicular acetylcholine transporter (VAChT). We
      find that lack of cardiomyocyte-secreted ACh disturbs the regulation of cardiac
      activity and causes cardiomyocyte remodeling. Mutant mice present normal
      hemodynamic parameters under nonstressful conditions; however, following
      exercise, their heart rate response is increased. Moreover, hearts from mutant
      mice present increased oxidative stress, altered calcium signaling, remodeling,
      and hypertrophy. Hence, without cardiomyocyte-derived ACh secretion, hearts from
      mutant mice show signs of imbalanced autonomic activity consistent with decreased
      cholinergic drive. These unexpected results suggest that cardiomyocyte-derived
      ACh is required for maintenance of cardiac homeostasis and regulates critical
      signaling pathways necessary to maintain normal heart activity. We propose that
      this non-neuronal source of ACh boosts parasympathetic cholinergic signaling to
      counterbalance sympathetic activity regulating multiple aspects of heart
      physiology.

PMID- 24018064
TI  - Identification of Sec14-like 3 as a novel lipid-packing sensor in the lung.
AB  - Pulmonary surfactant, a complex composed primarily of lipids and associated
      proteins, is synthesized in alveolar type II (ATII) cells and secreted into
      alveoli to prevent collapse during respiration. Although numerous studies have
      clarified the fundamental roles of pulmonary surfactant, the molecular mechanisms
      of transport and secretion of pulmonary surfactant remain totally unknown. Thus,
      we screened candidate genes by comparing genes with the expressed sequence tag
      (EST) libraries of embryonic and adult lungs by using the digital differential
      display method in the National Center for Biotechnology Information (NCBI)
      database. We identified Sec14-like 3 (Sec14L3) as a new class of lipid-associated
      proteins highly expressed in ATII cells. We found that Sec14L3 expression is >100
      fold increased during the perinatal period in the lung. Furthermore, Sec14L3
      bound to small-sized liposomes (30 nm in diameter), but not to large-sized
      liposomes (100 nm diameter), through its Sec14 domain. Because of the increased
      curvature, lipid-packing defects are more likely to occur in small-sized
      liposomes than in large-sized liposomes. Based on these results, we conclude that
      Sec14L3 is a new class of lipid-packing sensor. Sec14L3 may play important roles
      in the lung, such as intracellular lipid transport, surfactant maturation, and
      endo/exocytosis.

PMID- 24018065
TI  - Molecular determinants of desensitization in an ENaC/degenerin channel.
AB  - Epithelial Na(+) channel (ENaC)/degenerin family members are involved in
      mechanosensation, blood pressure control, pain sensation, and the expression of
      fear. Several of these channel types display a form of desensitization that
      allows the channel to limit Na(+) influx during prolonged stimulation. We used
      site-directed mutagenesis and chemical modification, functional analysis, and
      molecular dynamics simulations to investigate the role of the lower palm domain
      of the acid-sensing ion channel 1, a member of the ENaC/degenerin family. The
      lower palm domains of this trimeric channel are arranged around a central
      vestibule, at ~20 A above the plasma membrane and are covalently linked to the
      transmembrane channel parts. We show that the lower palm domains approach one
      another during desensitization. Residues in the palm co-determine the pH
      dependence of desensitization, its kinetics, and the stability of the
      desensitized state. Mutations of palm residues impair desensitization by
      preventing the closing movement of the palm. Overexpression of desensitization
      impaired channel mutants in central neurons allowed--in contrast to
      overexpression of wild type--a sustained signaling response to rapid pH
      fluctuations. We identify and describe here the function of an important
      regulatory domain that most likely has a conserved role in ENaC/degenerin
      channels.

PMID- 24018066
TI  - The musculoskeletal loading profile of the thumb during pipetting based on tendon
      displacement.
AB  - Strong evidence indicates that highly repetitive manual work is associated with
      the development of upper extremity musculoskeletal disorders (MSDs). One of the
      occupational activities that involves highly repetitive and forceful hand work is
      manual pipetting in chemical or biological laboratories. In the current study, we
      quantified tendon displacement as a parameter to assess the cumulative loading
      exposure of the musculoskeletal system in the thumb during pipetting. The maximal
      tendon displacement was found in the flexor pollicis longus (FPL) tendon.
      Assuming that subjects' pipetting rates were maintained constant during a period
      of 1 h, the average accumulated tendon displacement in the FPL reached 29 m,
      which is in the lower range of those observed in other occupational activities,
      such as typing and nail gun operations. Our results showed that tendon
      displacement data contain relatively small standard deviations, despite high
      variances in thumb kinematics, suggesting that the tendon displacements may be
      useful in evaluating the musculoskeletal loading profile.

PMID- 24018067
TI  - TNF-alpha, HGF and macrophage in peritumoural liver tissue relate to major risk
      factors of HCC Recurrence.
AB  - BACKGROUND/AIMS: Hepatocyte growth factor (HGF) responds to tumor necrosis factor
      alpha (TNF- alpha) secreted by macrophages and has been suggested to function in
      malignant metastasis. This study was performed to shed a light on the complicated
      relation between intrahepatic macrophages, TNF- alpha, HGF and hepatocellular
      carcinoma (HCC) microvascular invasion (MVI) and pathological grade. METHODOLOGY:
      Forty-eight HCC cases were divided into three groups according to pathological
      grade: poorly-differentiated (PD), moderately-differentiated (MD) and well
      differentiated (WD) groups. Each group was divided into subgroups based on the
      condition of MVI. Macrophages were counted, and TNF- alpha and HGF were tested in
      all specimens by immunohistochemical analysis and RT-PCR. RESULTS: In
      peritumoural liver tissue, MVI had more HGF (t=8.22, p<0.05) and less TNF- alpha
      (t=4.20, p<0.05) than non-MVI. With MVI, PD and MD had more TNF- alpha (t=3.30,
      p<0.05and t=2.82, p<0.05) than WD in peritumoural tissue. CONCLUSIONS:
      Overexpressed TNF- alpha and HGF in microenvironment were related to poor
      differentiation and microvascular invasion of HCC. We suggest that inflammation
      of hepatic microenvironment promote pathological degradation and microvascular
      invasion of HCC.

PMID- 24018068
TI  - Institutional abuse of children in the Austrian Catholic Church: types of abuse
      and impact on adult survivors' current mental health.
AB  - The aim of this study was to explore the nature and dimensions of institutional
      child abuse (IA) by the Austrian Catholic Church and to investigate the current
      mental health of adult survivors. Data were collected in two steps. First,
      documents of 448 adult survivors of IA (M=55.1 years, 75.7% men) who had
      disclosed their abuse history to a victim protection commission were collected.
      Different types of abuse, perpetrator characteristics, and family related risk
      factors were investigated. Second, a sample of 185 adult survivors completed the
      Posttraumatic Stress Disorder Checklist (PCL-C) and the Brief Symptom Inventory
      (BSI). Participants reported an enormous diversity of acts of violent physical,
      sexual, and emotional abuse that had occurred in their childhood. The majority of
      adult survivors (83.3%) experienced emotional abuse. Rates of sexual (68.8%) and
      physical abuse (68.3%) were almost equally high. The prevalence of PTSD was 48.6%
      and 84.9% showed clinically relevant symptoms in at least one 1 of 10 symptom
      dimensions (9 BSI subscales and PTSD). No specific pre-IA influence was found to
      influence the development of PTSD in later life (e.g. poverty, domestic
      violence). However, survivors with PTSD reported a significantly higher total
      number of family related risk factors (d=0.33). We conclude that childhood IA
      includes a wide spectrum of violent acts, and has a massive negative impact on
      the current mental health of adult survivors. We address the long-term effects of
      these traumatic experiences in addition to trauma re-activation in adulthood as
      both bear great challenges for professionals working with survivors. 

PMID- 24018069
TI  - Resident training in single-incision compared with traditional cholecystectomy.
AB  - INTRODUCTION: As attending surgeons' comfort with single-incision laparoscopic
      surgery (SILS) grows, and with continued improvement in surgical instruments,
      advanced laparoscopic techniques are increasingly being incorporated into
      surgical training. The aim of our study was to evaluate resident performance and
      patient outcomes in patients undergoing resident-performed SILS versus a resident
      performed traditional laparoscopic cholecystectomy (LC). METHODS: A retrospective
      case-control study of 80 patients undergoing elective surgical intervention with
      a resident-performed SILS (n = 20) or a resident-performed traditional LC (n =
      60) for gallbladder disease over a 15-month period was performed. Surgical
      indications, common perioperative variables, complications, and length of stay
      were reviewed, and all variables were evaluated for statistical significance.
      RESULTS: Median operative times were similar for the resident-performed SILS
      cohort and the resident-performed traditional LC cohort (70.0 minutes and 66.0
      minutes, respectively; P = .54). There were no complications in either the
      resident-performed SILS or resident-performed traditional LC groups. There was no
      difference in mean length of hospital stay between the resident-performed SILS
      group and resident-performed traditional LC group (0.95 days and 1.10 days,
      respectively; P = .50). CONCLUSION: Our data strongly support the ability to
      train senior residents to complete a SILS technique safely and with the same
      efficacy as with traditional LC.

PMID- 24018070
TI  - Is laparoscopy a risk factor for bile duct injury during cholecystectomy?
AB  - BACKGROUND AND OBJECTIVES: Previously, risk factors for bile duct injury have
      been identified as acute cholecystitis, male gender, older age, aberrant biliary
      anatomy, and laparoscopic cholecystectomy. METHODS: A retrospective analysis of
      the Nationwide Inpatient Sample from 1998 to 2006 was performed with an inclusion
      criterion of cholecystectomy performed on hospital day 0 or 1. Patient- and
      hospital-level factors potentially associated with bile duct injury were examined
      by logistic regression. RESULTS: A total of 377,424 cholecystectomy patients were
      identified. There were 1124 bile duct injuries (0.30%), with 177 (0.06%) in the
      laparoscopic cholecystectomy group and 947 (1.46%) in the open cholecystectomy
      group (P < .001). On multivariate analysis, significant risk factors for bile
      duct injury were male gender (odds ratio [OR], 1.21; 95% confidence interval
      [CI], 1.06-1.38; P = .006), age >60 years (OR, 2.23; 95% CI, 1.61-3.09; P <
      .001), and academic hospital status (OR, 1.37; 95% CI, 1.05-1.79; P = .02). Acute
      cholecystitis was associated with a lower risk of bile duct injury (OR, 0.67; 95%
      CI, 0.46-0.99; P = .044). CONCLUSION: Independent risk factors for bile duct
      injury included male gender, age >60 years, and academic hospital status.
      Laparoscopic cholecystectomy, obesity, insurance status, or hospital volume was
      not associated with an increased risk of bile duct injury.

PMID- 24018071
TI  - Post-endoscopic retrograde cholangiography laparoscopic cholecystectomy:
      challenging but safe.
AB  - BACKGROUND AND OBJECTIVES: Up to 19% of patients undergoing laparoscopic
      cholecystectomy (LC) have common bile duct stones and may require endoscopic
      retrograde cholangiography (ERCP) before LC. The risk of complications of LC
      after ERCP is higher, and the optimal interval between ERCP and LC is disputed.
      In our unit, LC is performed approximately 6 weeks after ERCP. This study aims to
      compare outcomes between subsets of patients undergoing LC with or without prior
      ERCP. METHODS: All patients undergoing ERCP and elective laparoscopic
      cholecystectomy (ELC) over a 1-year period were included. Outcome measures
      included ERCP outcomes, duration of surgery, intraoperative findings, and
      postoperative outcomes. Two groups of patients were compared: LC after ERCP and
      ELC. RESULTS: The study included 190 ELC patients and 43 patients with LC after
      ERCP (ERCP-LC) (December 2008 to December 2009). At ERCP, 25 patients (58%) had
      ductal stones. The post-ERCP complication rate was 5%. The median time to LC was
      42 days, and 6 patients (14%) were readmitted before LC. There were more severe
      adhesions and longer median operating times in the ERCP-LC group (75 minutes for
      ELC vs 110 minutes for ERCP-LC, P = .013). We found no significant differences in
      rates of conversion to open surgery, postoperative complications, lengths of
      stay, and readmission rates. CONCLUSION: Interval LC after ERCP is a more
      technically challenging procedure but is associated with a low rate of
      complications. Although there is emerging evidence that early LC after ERCP is
      feasible, our study shows that our current practice of delaying LC by
      approximately 6 weeks is safe.

PMID- 24018072
TI  - The learning curve of laparoendoscopic single-Site (LESS) fundoplication:
      definable, short, and safe.
AB  - BACKGROUND AND OBJECTIVES: This study of laparoendoscopic single-site (LESS)
      fundoplication for gastroesophageal reflux disease was undertaken to determine
      the "learning curve" for implementing LESS fundoplication. METHODS: One hundred
      patients, 38% men, with a median age of 61 years and median body mass index of 26
      kg/m(2) , underwent LESS fundoplications. The operative times, placement of
      additional trocars, conversions to "open" operations, and complications were
      compared among patient quartiles to establish a learning curve. Median data are
      reported. RESULTS: The median operative times and complications did not differ
      among 25-patient cohorts. Additional trocars were placed in 27% of patients, 67%
      of whom were in the first 25-patient cohort. Patients undergoing LESS
      fundoplication had a dramatic relief in the frequency and severity of all
      symptoms of reflux across all cohorts equally (P < .05), particularly for
      heartburn and regurgitation, without causing dysphagia. CONCLUSION: LESS
      fundoplication ameliorates symptoms of gastroesophageal reflux disease without
      apparent scarring. Notably, few operations required additional trocars after the
      first 25-patient cohort. Patient selection became more inclusive (eg, more "redo"
      fundoplications) with increasing experience, whereas operative times and
      complications remained relatively unchanged. The learning curve of LESS
      fundoplication is definable, short, and safe. We believe that patients will seek
      LESS fundoplication because of the efficacy and superior cosmetic outcomes;
      surgeons will need to meet this demand.

PMID- 24018073
TI  - Single-incision versus conventional laparoscopic adjustable gastric banding.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic adjustable gastric banding is an
      effective and popular bariatric surgery for weight loss in obese patients that
      traditionally involves up to 5 incisions. Recently, a more minimally invasive
      single-incision technique has been developed. In this retrospective study, we
      compare conventional and single-incision laparoscopic adjustable gastric banding
      with regard to weight loss and complication rates in a cohort of demographically
      similar patients. METHODS: From February 2009 to February 2010, 59 patients
      underwent laparoscopic adjustable gastric banding by one surgeon at an outpatient
      surgery center. All patients were compared by age, sex, preoperative body mass
      index, 30-day complication rates, and excess weight loss. Thirty-seven operations
      were performed by a conventional, 5-incision technique, whereas 22 patients
      underwent the single-incision technique. The success of these techniques was
      determined by comparing complication rates and average percentage excess weight
      loss at 6-month follow-up intervals. RESULTS: Patients who underwent conventional
      laparoscopic adjustable gastric banding had a mean age of 41.2 years and
      preoperative body mass index of 48.2 kg/m(2) compared with 43.9 years and 40.3
      kg/m(2), respectively, for the single-incision patients. The mean operative time
      in the single-incision group was longer than that in the conventional group: 47.1
      minutes versus 37.4 minutes (P = .0027). The overall percentage excess weight
      loss was not statistically different between the 2 groups for each follow-up
      period. There were no complications or deaths in either group. CONCLUSION:
      Although patients undergoing bariatric surgery may choose the single-incision
      technique for cosmetic purposes, this retrospective review comparing single
      incision and conventional laparoscopic adjustable gastric banding shows longer
      operative times with equivalent weight loss and morbidity.

PMID- 24018074
TI  - Anatomic landmarks in the sleeve gastrectomy.
AB  - BACKGROUND AND OBJECTIVES: The vertical sleeve gastrectomy is a common bariatric
      procedure. The operation is relatively standard, but there are still variations
      among surgeons. The two main variations are bougie size and extent of distal
      resection. Some surgeons will start the gastric resection at 2 cm proximal to the
      pylorus, whereas others start at 6 cm. Our hypothesis is that there are anatomic
      landmarks that are constant and can be used to help standardize the procedure.
      METHODS: Twenty-eight morbidly obese patients undergoing laparoscopic bariatric
      surgery (gastric bypass or sleeve gastrectomy) had the distance from the pylorus
      to the second branch of the right gastroepiploic artery on the inferior border of
      the greater curvature of the stomach measured. Body mass index, height, weight,
      age, and sex were also analyzed. RESULTS: The study comprised 22 women and 6 men
      with a mean age of 46.2 years (range, 22-68 years). The mean body mass index was
      43.2 kg/m(2) (range, 37.2-62.4 kg/m(2)). The mean distance from the pylorus to
      the second branch of the right gastroepiploic vessel was 4.52 cm (range, 3.5-5.5
      cm). CONCLUSION: The second branch of the right gastroepiploic artery can be used
      as a constant anatomic landmark. It is found about 4.5 cm from the pylorus. This
      can be safely used as a landmark for marking the distal extent of resection
      during a vertical sleeve gastrectomy and obviates the need to formally measure
      the distance from the pylorus.

PMID- 24018075
TI  - A systematic review of staple-line reinforcement in laparoscopic sleeve
      gastrectomy.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic sleeve gastrectomy is gaining popularity
      as a bariatric procedure, with outcomes similar to gastric band and gastric
      bypass. Staple-line disruption is a significant source of morbidity and death. We
      aim to evaluate the effect of staple-line reinforcement on the gastric leak rate,
      morbidity, and mortality rate. METHODS: A systematic review was performed using
      title key words "sleeve gastrectomy," and articles were reviewed for description
      of operative technique and postoperative outcomes including staple-line leak.
      Rates of leak, bleeding, surgical-site infection, reintervention, readmission,
      and mortality were analyzed. We calculated pooled event rates and 95% confidence
      intervals using fixed-effects modeling to determine differences between the
      reinforcement group (group A) and non-reinforcement group (group B). RESULTS: We
      identified 390 articles, and 30 met the inclusion criteria. Group A had 3293
      patients, and group B had 1588 patients. After heterogeneity calculations, 9
      variables met the criteria to be analyzed. The leak rate was 3.9% (95% confidence
      interval, 2.9%-5.5%) in group A and 3.2% (95% confidence interval, 2.8%-4.1%) in
      group B. The mortality rate was 0.8% (95% confidence interval, 0.4%-1.5%) in
      group A and 0.7% (95% confidence interval, 0.4%-1.1%) in group B. Our results
      also showed no statistical difference for any of our other 7 outcome variables.
      CONCLUSION: Our study shows a lack of statistical difference in leak rate,
      overall morbidity, or mortality rate in laparoscopic sleeve gastrectomy with or
      without staple-line reinforcement. Because of study limitations, we propose that
      prospective trials are needed to determine the effect of staple-line
      reinforcement on leak rates.

PMID- 24018076
TI  - Robotic versus abdominal hysterectomy for very large uteri.
AB  - BACKGROUND AND OBJECTIVES: We sought to examine the outcomes of patients with
      myomatous uteri weighing >1000 g who underwent hysterectomy by one of two
      modalities, either with a robotic system or by laparotomy. METHODS: All patients
      who underwent robotic hysterectomy for uteri weighing >1000 g at our institution
      between May 2007 and January 2011 were identified, and a retrospective chart
      review was performed. These patients were matched to a laparotomy control group
      by body mass index and uterine weight, and the postoperative outcomes in both
      groups were analyzed and compared. RESULTS: Sixty patients with uteri weighing
      >1000 g underwent hysterectomy, 30 with the robotic system and 30 by laparotomy.
      The median body mass index was 31.8 kg/m(2) (range, 18.5-56.3 kg/m(2)) and the
      median uterine weight was 1259 g (range, >1000 -3543 g) in the robotic group
      versus 30.2 kg/m(2) (range, 18 - 48 kg/m(2)) and 1509 g (range, 1000 -3570 g),
      respectively, in the laparotomy group (P = .31). The median operating time was
      255 minutes (range, 180 -372 minutes) in the robotic group versus 150 minutes
      (range, 100 -285 minutes) in the laparotomy group (P < .001). There were no
      conversions to laparotomy. In both groups the operative time was not increased
      with increasing specimen weight. The median blood loss was 150 mL in the robotic
      group versus 425 mL in the laparotomy group. Of 30 patients in the robotic group,
      23 (76.6%) were discharged from the hospital on postoperative day 1. The median
      hospital stay for the robotic group was 1 day, and for the laparotomy group, it
      was 2.5 days (P < .01). CONCLUSION: Robotic surgeries for very large myomatous
      uteri are feasible and have minimal morbidity even in morbidly obese patients.
      The robotic surgery requires a longer operative time but results in a shorter
      hospital stay and decreased intraoperative blood loss.

PMID- 24018077
TI  - Postoperative outcomes after robotic versus abdominal myomectomy.
AB  - BACKGROUND AND OBJECTIVES: Differences in postoperative outcomes comparing
      robotic-assisted laparoscopic myomectomy (RALM) with abdominal myomectomy (AM)
      have rarely been reported. The objective of this study was to compare surgical,
      quality-of-life, and residual fibroid outcomes after RALM and AM. METHODS:
      Consecutive patients who underwent RALM (n = 16) were compared with AM patients
      (n = 23) presenting with a uterine size of <20 weeks. Study patients participated
      in a telephone interview at 6 weeks and underwent a no-cost ultrasonographic
      examination at 12 weeks after surgery to obtain quality-of-life and residual
      fibroid outcomes. Medical records were reviewed to obtain surgical outcomes.
      RESULTS: Longer operative times (261.1 minutes vs 124.8 minutes, P < .001) and a
      3-fold unfavorable difference in operative efficiency (73.7 g vs 253.0 g of
      specimen removed per hour, P < .05) were observed with RALM compared with AM.
      Patients undergoing RALM had shorter lengths of hospital stay (1.5 days vs 2.7
      days, P < .001). Reduction of patient symptoms and overall satisfaction were
      equal. RALM patients were more likely to be back to work within 1 month (85.7% vs
      45.0%, P < .05). Residual fibroid volume in the RALM group was 5 times greater
      than that in the AM group (17.3 cm(3) vs 3.4 cm(3), P < .05). CONCLUSION: RALM
      and AM were equally efficacious in improving patient symptoms. Although operative
      times were significantly longer with RALM, patients had a quicker recovery,
      demonstrated by shortened lengths of stay and less time before returning to work.
      However, greater residual fibroid burden was observed with RALM when measured 12
      weeks after surgery.

PMID- 24018079
TI  - Robotic hysterectomy strategies in the morbidly obese patient.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to present strategies
      for performing computer-enhanced telesurgery in the morbidly obese patient.
      METHODS: This was a prospective, institutional review board-approved, descriptive
      feasibility study (Canadian Task Force classification II-2) conducted at a
      university-affiliated hospital. Twelve class III morbidly obese women with a body
      mass index of 40 kg/m(2) or greater were selected to undergo robotic-assisted
      total laparoscopic hysterectomy. Robotic-assisted total laparoscopic
      hysterectomy, classified as type IVE, with complete detachment of the cardinal
      uterosacral ligament complex, unilateral or bilateral, with entry into the vagina
      was performed. RESULTS: The median estimated blood loss was 146.3 mL (range, 15
      550 mL), the mean length of stay in the hospital was 25.3 hours (range, 23- 48
      hours), and the complication rate was 0%. The rate of conversion to laparotomy
      was 8%. The median surgical time was 109.6 minutes (range, 99 -145 minutes).
      CONCLUSION: Robotic-assisted total laparoscopic hysterectomy can be a safe and
      effective method of performing hysterectomies in select morbidly obese patients,
      allowing them the opportunity to undergo minimally invasive surgery without
      increased perioperative complications.

PMID- 24018078
TI  - Effects of electrosurgery and vaginal closure technique on postoperative vaginal
      cuff dehiscence.
AB  - BACKGROUND AND OBJECTIVES: The aim of our study is to evaluate the role of
      electrosurgery and vaginal closure technique in the development of postoperative
      vaginal cuff dehiscence. METHODS: From prospective surgical databases, we
      identified 463 patients who underwent total laparoscopic hysterectomy (TLH) for
      benign disease and 147 patients who underwent laparoscopic-assisted vaginal
      hysterectomy (LAVH) for cancer. All TLHs and LAVHs were performed entirely by use
      of electrosurgery, including colpotomy. Colpotomy in the TLH group was performed
      with Harmonic Ace Curved Shears (Ethicon Endo-Surgery, Cincinnati, OH, USA), and
      in the LAVH group, it was performed with a monopolar electrosurgical pencil. The
      main surgical difference was vaginal cuff closure--laparoscopically in the TLH
      group and vaginally in the LAVH group. RESULTS: Although patients in the LAVH
      group were at increased risk for poor healing (significantly older, higher body
      mass index, more medical comorbidities, higher blood loss, and longer operative
      time), there were no vaginal cuff dehiscences in the LAVH group compared with 17
      vaginal cuff dehiscences (4%) in the TLH group (P = .02). CONCLUSION: It does not
      appear that the increased vaginal cuff dehiscence rate associated with TLH is due
      to electrosurgery; rather, it is due to the vaginal closure technique.

PMID- 24018080
TI  - The role of cryosurgery of the prostate for nonsurgical candidates.
AB  - INTRODUCTION: Technological advancements have reduced the morbidity associated
      with cryosurgery, leading to an increased interest in this modality for the
      treatment of organ-confined prostate cancer. In this study, we critically examine
      the current role of cryoablation of the prostate to better understand how to
      counsel patients regarding this treatment option. METHODS: A database was
      compiled over a 3-year period (2008-2011) of 30 patients who underwent
      cryoablation for organ-confined prostate cancer. Indications for cryosurgery
      included primary treatment, focal treatment (institutional review board-approved
      prospective study), and salvage cryotherapy for radiation failure. The primary
      outcomes were biochemical response via prostate-specific antigen (PSA)
      measurement and morbidity associated with cryoablation. Cryotherapy failure was
      defined as an increasing postcryotherapy PSA level >= 2 ng/mL above the post
      treatment nadir, a positive prostate biopsy, or radiographic evidence of
      metastatic disease. RESULTS: Of the 30 patients who underwent cryoablation from
      2008 to 2011, 26 patients had complete follow-up data for analysis. Of these
      patients, 17 (65.38%) had total gland cryotherapy, 5 (19.23%) had salvage
      cryotherapy for radiation failure, and 4 (15.38%) had focal cryotherapy. The mean
      patient age was 68 years (54-89); median preoperative PSA was 5.5 ng/mL (1.7
      15.9); median prostate volume was 35 mL (15-54); mean Gleason score was 7; and
      the median PSA at study conclusion was 0.7 (0.02-3.4) ng/mL. Of the 17 patients
      who had total prostate cryotherapy, 11 (64.7%) had significant factors precluding
      primary treatment by a surgical and/or radiation approach, including neurological
      disorders (2), morbid obesity (1), rectal cancer treated with radiation (1),
      kidney/pancreas transplant (2), ileoanal pouch secondary to inflammatory bowel
      disease (IBD) (1), renal failure (1), and age (3). There were no intra- or
      postoperative complications. After a median follow-up of 18 months (1-40), none
      of the patients with multiple comorbidities had biochemical failures. Two
      patients from the salvage group experienced treatment failure requiring androgen
      deprivation therapy. CONCLUSIONS: This critical analysis of a single-surgeon
      experience at a large academic prostate cancer program revealed that the
      contemporary role of cryosurgery is, in select patients with comorbidities,
      preventing surgical and/or radiation therapy. Additionally, cryosurgery has a
      role in treating radiation failures. Further studies are necessary to investigate
      focal cryotherapy as an option for primary treatment, but our preliminary results
      are promising, without any biochemical failures in our focal therapy cohort.

PMID- 24018081
TI  - Laparoscopy to evaluate scrotal edema during peritoneal dialysis.
AB  - BACKGROUND: Acute scrotal edema is an infrequent complication in patients who
      undergo continuous ambulatory peritoneal dialysis (CAPD), occurring in 2% to 4%
      of patients. Inguinal hernia is usually the cause, but the diagnosis is sometimes
      confusing. Imaging modalities such as computed tomographic peritoneography are
      helpful but can be equivocal. We have used diagnostic laparoscopy in conjunction
      with open unilateral or bilateral hernia repair for diagnosis and treatment of
      peritoneal dialysis (PD) patients with acute scrotal edema. TECHNIQUE AND CASES:
      Three patients with acute scrotal edema while receiving CAPD over the span of 7
      years had inconclusive results at clinical examination and on diagnostic imaging.
      All patients underwent diagnostic laparoscopy that revealed indirect inguinal
      hernia, which was concomitantly repaired using an open-mesh technique. RESULTS:
      Diagnostic laparoscopy revealed the etiology of the scrotal edema 100% of the
      time, with no complications, and allowed concomitant repair of the hernia. One
      patient had postoperative catheter outflow obstruction, which was deemed to be
      unrelated to the hernia repair. CONCLUSION: Diagnostic laparoscopy is helpful in
      confirming the source of acute scrotal edema in CAPD patients and can be
      performed in conjunction with an open-mesh repair with minimal added time or
      risk.

PMID- 24018082
TI  - Laparoscopic adrenalectomy for nonfamilial adrenal medullary hyperplasia.
AB  - BACKGROUND AND OBJECTIVES: Sporadic adrenomedullary hyperplasia (AMH) is
      characterized by a medical history of hypertension, excessive catecholamine
      excretion, and histomorphometric evidence of increased adrenomedullary tissue
      relative to the cortex in the absence of multiple endocrine neoplasia. The aim of
      this study was to perform a retrospective analysis of patients after laparoscopic
      adrenalectomy for AMH, an early form of sporadic adrenal medulla-related
      endocrine hypertension, as well as to update our understanding of the clinical
      features and management of this clinicomorphologic entity. METHODS: We performed
      a retrospective review of the medical records of patients operated on between
      2007 and 2011 at Reina Sofia University General Hospital, Murcia, Spain, with a
      diagnosis of AMH. Patient characteristics, diagnostic studies, surgical
      procedures, and histologic findings were analyzed. RESULTS: Seven hypertensive
      patients with intermittent adrenergic crises were found to have AMH (3 men and 4
      women; mean age, 44 years). Catecholamine levels were increased. Radiologic
      studies included 1 or more of the following: magnetic resonance imaging, computed
      tomography, positron emission tomography imaging with fluorodeoxyglucose,
      dihydroxyphenylalanine-positron emission tomography-computed tomography,
      Octreoscan (Mallinckrodt Pharmaceuticals, St. Louis, MO, USA) and (123)I
      metaiodobenzylguanidine scintigraphy. Laparoscopic adrenalectomy was performed in
      all cases. One patient underwent bilateral adrenalectomy because of persistent
      symptomatology after unilateral adrenalectomy. Surgery was associated with
      normalization of catecholamine hypersecretion and complete disappearance of
      symptoms, as well as the reduction or abstention of antihypertensive therapy.
      CONCLUSIONS: Sporadic AMH is a clinicomorphologic entity that may mimic
      pheochromocytoma clinically. Recent advances in diagnostic and surgical methods
      have changed the management and outcome of this unusual disease. Laparoscopic
      adrenalectomy may be recommended as the gold standard in the treatment of this
      entity. Definitive diagnosis is provided by histologic study.

PMID- 24018083
TI  - Use of collapsible box trainer as a module for resident education.
AB  - BACKGROUND AND OBJECTIVES: We sought to determine whether training with a simple
      collapsible mobile box trainer leads to improved performance of fundamental
      laparoscopic skills (FLSs) during a 6-month interval versus validated
      laparoscopic box trainers and virtual-reality trainers, only accessible at a
      simulation training center. METHODS: With institutional review board approval, 20
      first- and second-year general surgery residents were randomized to scheduled
      training sessions in a surgical simulation laboratory or training in the use of a
      portable, collapsible Train Anywhere Skill Kit (TASKit) (Ethicon Endo-Surgery
      Cincinnati, OH, USA) trainer. Training was geared toward the FLS set for a skill
      assessment examination at a 6-month interval. RESULTS: The residents who trained
      with the TASKit performed the peg-transfer, pattern-cut exercise, Endoloop, and
      intracorporeal knot-tying FLS tasks statistically more efficiently during their 6
      month assessment versus their initial evaluation as compared with the group
      randomized to the simulation laboratory training. CONCLUSIONS: Using a simple
      collapsible mobile box trainer such as the TASKit can be a cost-effective method
      of training and preparing residents for FLS tasks considering the current cost
      associated with virtual and highdefinition surgical trainers. This mode of
      surgical training allows residents to practice in their own time by removing
      barriers associated with simulation centers.

PMID- 24018084
TI  - Construct validity of an inanimate training model for laparoscopic appendectomy.
AB  - BACKGROUND AND OBJECTIVE: The use of training models in laparoscopic surgery
      allows the surgical team to practice procedures in a safe environment. The aim of
      this study was to determine the capability of an inanimate laparoscopic
      appendectomy model to discriminate between different levels of surgical
      experience (construct validity). METHODS: The performance of 3 groups with
      different levels of expertise in laparoscopic surgery--experts (Group A),
      intermediates (Group B), and novices (Group C)--was evaluated. The groups were
      instructed of the task to perform in the model using a video tutorial. Procedures
      were recorded in a digital format for later analysis using the Global Operative
      Assessment of Laparoscopic Skills (GOALS) score; procedure time was registered.
      The data were analyzed using the analysis of variance test. RESULTS: Twelve
      subjects were evaluated, 4 in each group, using the GOALS score and time required
      to finish the task. Higher scores were observed in the expert group, followed by
      the intermediate and novice groups, with statistically significant difference.
      Regarding procedure time, a significant difference was also found between the
      groups, with the experts having the shorter time. The proposed model is able to
      discriminate among individuals with different levels of expertise, indicating
      that the abilities that the model evaluates are relevant in the surgeon's
      performance. CONCLUSIONS: Construct validity for the inanimate full-task
      laparoscopic appendectomy training model was demonstrated. Therefore, it is a
      useful tool in the development and evaluation of the resident in training.

PMID- 24018085
TI  - Laparoscopic undiversion in a child with sacral agenesis into augmentation
      cystoplasty.
AB  - INTRODUCTION: In neurogenic bladder with compromised renal function or when
      complex reconstruction is not preferred, ileal conduit is considered. Undiversion
      is performed when the patient prefers the procedure, once the renal function
      improves, or when complications resulting from diversion are present. CASE
      DESCRIPTION: We present the case of a 10-y-old boy with sacral agenesis, who
      underwent laparoscopic-assisted ileal conduit diversion in 2006, because he had a
      grossly unstable, small-capacity bladder and was not compliant with intermittent
      self-catheterization. At present, he preferred not to have a conduit. DISCUSSION:
      Laparoscopic undiversion with ileal augmentation cystoplasty was performed. The
      postoperative course was uneventful, and he is now on intermittent self
      catheterization with healthy renal function. Laparoscopic undiversion is
      technically challenging, yet feasible, and is an effective option in children. To
      our knowledge, this is the first such case reported.

PMID- 24018086
TI  - Laparoscopic resection of antenataly identified duodenal duplication cyst.
AB  - We report the first case of complete laparoscopic resection of a duodenal
      duplication cyst (DDC) in an 8-mo-old patient. The cyst was diagnosed by routine
      antenatal ultrasound performed at 3 mo of gestational age. Although the baby was
      born asymptomatic without any congenital abnormalities, the cyst had continued to
      increase on serial sonographic examinations. Previous reports have described
      treatment of DDC by surgical resection (laparotomy) or endoscopic
      marsupialization; we describe here, the first report of laparoscopic approach to
      resect DDC in a pediatric patient with a favorable outcome. 

PMID- 24018087
TI  - Laparoscopic management of a large duodenal lipoma presented as gastric outlet
      obstruction.
AB  - Lipoma of the duodenum is a rare tumor, with fewer than 230 cases reported to
      date. A majority of these tumors were managed by endoscopic and open surgical
      intervention, with published data on one case that was managed by total
      laparoscopy. We report a case of a 43-year-old woman with signs and symptoms of
      gastric outlet obstruction who was diagnosed as having a large duodenal lipoma
      that was managed successfully with laparoscopic excision. 

PMID- 24018088
TI  - Re-do Roux-en-Y gastric bypass in a patient with known midgut malrotation.
AB  - A 40-year-old woman presented with small bowel obstruction caused by an internal
      hernia through Peterson's defect. The patient was known to have midgut
      malrotation (MM) and also had laparoscopic Roux-en-Y gastric bypass for morbid
      obesity 6 years prior. An open revision of Roux-en-Y gastric bypass was performed
      as a result of ischemia of alimentary limb. She made a slow but uneventful
      recovery and was discharged home. MM is a rare congenital anomaly that requires
      the surgeon to be well aware of the unique variation in anatomy to perform a
      mirror image of the routine Roux-en-Y gastric bypass. At the end of this case
      report, we present a short literature review of published data related to MM
      encountered during Roux-en-Y gastric bypass. 

PMID- 24018089
TI  - Laparoscopic-assisted vesicocalicostomy for severe pelvi-ureteral stricture
      disease.
AB  - A 39-year-old female previously treated with shock wave lithotripsy developed
      extensive ureteral stricture disease. After 2 unsuccessful attempts at retrograde
      balloon dilatation, she was evaluated at our center for further management.
      Successful reconstruction was performed with laparoscopic-assisted
      vesicocalicostomy. 

PMID- 24018090
TI  - Single-incision sleeve gastrectomy for successful treatment of a gastrointestinal
      stromal tumor.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors
      that are located specifically in the gastrointestinal tract, with up to 60% of
      occurrences in the stomach, 30% in the small intestine, and 10% in the esophagus,
      colon, and rectum. The annual incidence of GISTs is about 15 cases per million,
      which in the United States equals 5000 cases per year. In most cases, these
      tumors are asymptomatic and are found incidentally on computed tomography scan or
      by endoscopy. Preoperative evaluation is based on location, size, and anatomic
      features and helps to confirm the diagnosis of the GIST and assess outcomes.
      Surgical intervention is the gold standard for treatment of nonmetastatic GISTs.
      CASE PRESENTATION: We report the case of an 80-year-old man with a gastric mass
      on the posterior surface of the greater curvature of the stomach at the junction
      of the gastric antrum and the pylorus, found incidentally on a computed
      tomography scan. The patient underwent a diagnostic laparoscopy and a single
      incision laparoscopic sleeve gastrectomy. After histologic evaluation, the
      resected lesion was determined to be a gastrointestinal stromal tumor.
      CONCLUSION: A single-incision laparoscopic sleeve gastrectomy for the resection
      of GISTs is a feasible and appropriate method if the lesion is a safe distance
      from the pylorus and the gastroesophageal junction for gross negative margins to
      be obtained. Its advantages include decreased pain and a shorter hospital stay
      compared with other methods.

PMID- 24018091
TI  - Delayed massive bleeding two years after Roux-en-Y gastric bypass.
AB  - INTRODUCTION: Delayed massive bleeding from an ischemic ulcer is a complication
      after Roux-en-Y gastric bypass (RYGB). Ischemic ulcers that present with massive
      bleeding are rare and challenging for the gastroenterologist as well as the
      bariatric surgeon. CASE DESCRIPTION: This report reviews the case of a 63-year
      old man who underwent an uncomplicated laparoscopic RYGB for morbid obesity and
      experienced two episodes of massive hemorrhage after the procedure, almost 1 year
      apart. CONCLUSION: To our knowledge, there are only a few such specific cases
      reported. Here, we describe the treatment and outcome for such a case and present
      a review of the literature.

PMID- 24018092
TI  - Healing of complicated gastric leaks in bariatric patients using endoscopic
      clips.
AB  - INTRODUCTION: Endoscopists have used clipping devices to successfully close
      acute, iatrogenic perforations throughout the gastrointestinal tract. We applied
      this technology to our bariatric patients, who tend to present with a more
      delayed anastomotic leak, to determine whether these leaks and fistulae would
      also heal with endoclip application. CASE DESCRIPTION: We describe a small series
      of 2 clinically stable bariatric patients who presented with postoperative
      anastomotic leaks who met criteria for non-operative therapy. The first underwent
      a laparoscopic Roux-en-Y gastric bypass and presented postoperatively with a leak
      at her gastrojejunal anastomosis. The location was not amenable to stent
      placement; therefore, 2 endoclips were placed. The leak was sealed by
      fluoroscopic examination 14 d later. The second had a reversal of a previous
      gastric bypass, creating a new gastrogastric anastomosis. A leak was found at
      this new connection postoperatively. After failure of a stent to seal the leak, 8
      endoclips were used. This patient also had successful closure of her leak on
      fluoroscopy 14 d postprocedure. DISCUSSION: Anastomotic leaks after bariatric
      surgery can incur severe morbidity, cost, and detriment to patients' quality of
      life. Unstable patients require operative intervention. Stable patients are
      candidates for more-conservative measures. Endoscopic stents have been successful
      in closing gastric leaks, though some are not anatomically amenable to stent
      placement, and stents also have the potential to migrate distally. We demonstrate
      2 cases of successful closure of leaks in bariatric patients by using endoclips
      and suggest that this be considered an option in appropriate cases.

PMID- 24018093
TI  - Cecal bascule after laparoscopic ventral hernia repair.
AB  - INTRODUCTION: We present a case of a cecal bascule, a rare type of cecal
      volvulus, as a complication of a laparoscopic ventral hernia repair. CASE
      DESCRIPTION: A 73-y-old male with a ventral hernia underwent an uneventful
      elective laparoscopic repair. He developed an acute abdomen on postoperative day
      6, and imaging demonstrated a cecal bascule. Exploratory laparotomy revealed a
      cecal bascule with an ischemic and perforated cecum, and a right hemicolectomy
      was performed. DISCUSSION: Laparoscopic tension-free ventral hernia repairs have
      become more common, especially for obese patients. We discuss some risk factors
      that can predispose a patient to having a cecal volvulus postoperatively.
      Although cecal volvulus is a very rare complication after laparoscopic surgery,
      it can result in serious complications.

PMID- 24018094
TI  - Laparoscopic adrenalectomy in a patient with situs inversus.
AB  - BACKGROUND: Situs inversus is a relatively rare congenital disease. A patient
      with a right adrenal tumor complicated by total situs inversus was treated by
      laparoscopy. CASE DISCUSSION: The patient was a 45-y-old male with lower limb
      weakness. He had been diagnosed with situs inversus during a general health check
      up as an infant. His blood pressure was 230/160 mm Hg, and the serum potassium
      level was 2.0 mEq/L. Abdominal ultrasonography and magnetic resonance imaging
      showed a mass of about 2cm in diameter in contact with the right adrenal gland.
      Total situs inversus was simultaneously confirmed. The plasma aldosterone
      concentration was elevated to 442pg/mL, and renin activity was suppressed, at
      0.3ng/mL/hr. DISCUSSION: These findings indicated a diagnosis of primary
      aldosteronism due to an adrenal tumor, and the right adrenal tumor was resected
      laparoscopically. The right adrenal gland was approached and resected from the
      lateral side of the spleen, which was located on the right side because of situs
      inversus. The resected specimen was 4.5cm x 1.6cm, and no intraoperative
      complications occurred. The histopathological examination showed the tumor to be
      an aldosterone-producing adrenocortical adenoma.

PMID- 24018095
TI  - A novel nonoperative approach to abdominal compartment syndrome after abdominal
      wall reconstruction.
AB  - INTRODUCTION: Intraabdominal hypertension and abdominal compartment syndrome have
      been increasingly recognized as significant causes of morbidity and mortality in
      both medical and surgical patients. The gold standard remains surgical
      intervention; however, nonoperative approaches have been investigated less. Here,
      we describe the successful treatment of a severe acute case by intubation,
      nasogastric decompression, and paralysis--a novel approach not previously
      described in the literature. CASE DESCRIPTION: After the patient underwent
      laparoscopic bilateral component separation and repair of a large recurrent
      ventral hernia with a 20 30-cm Strattice mesh (LifeCell Corp, Branchburg, NJ),
      acute renal failure developed within 12 hours postoperatively, and was associated
      with oliguria, hyperkalemia, and elevated peak airway and bladder pressures. The
      patient was treated nonoperatively with intubation, nasogastric tube
      decompression, and paralysis with a vecuronium drip. Rapid reversal was seen,
      avoiding further surgery. Within 2 hours after intubation and paralysis, our
      patient's urine output improved dramatically with an initial diuresis of
      approximately 1 L, his bladder pressures decreased, and within 12 hours his
      creatinine level had normalized. DISCUSSION: Although surgical intervention has
      traditionally been thought of as the most effective--and thus the gold standard-
      for abdominal compartment syndrome, this preliminary experience demonstrates
      nonoperative management as highly efficacious, with the added benefit of
      decreased morbidity. Therefore, nonoperative management could be considered first
      line therapy, with laparotomy reserved for refractory cases only. This suggests a
      more complex pathology than the traditional teaching of congestion and edema
      alone.

PMID- 24018096
TI  - Delayed presentation of a bowel Bovie injury after laparoscopic ventral hernia
      repair.
AB  - INTRODUCTION: Bowel injury during laparoscopic surgery is a rare but serious
      complication. A Bovie injury to the bowel can cause delayed perforation of the
      viscus, thus increasing the possibility of a preventable morbidity. Patients
      presenting with perforation peritonitis within 24 hours and up to 2 to 3 weeks
      after laparoscopic Bovie injury to the bowel have been reported in the
      literature. CASE DESCRIPTION: A 74-year-old woman underwent a laparoscopic
      ventral hernia mesh repair. Intraoperatively, a small area of superficial Bovie
      injury to the small bowel was repaired with Lembert sutures and tissue glue.
      Postoperatively, the patient recovered well, but she presented with perforation
      peritonitis 3 months after surgery. An exploratory laparotomy showed a jejunal
      perforation in the same area that was injured with cautery and repaired during
      the previous surgery. The patient was only using inhaled steroids for asthma on
      and off but had a remote history of chemotherapy and radiation for colorectal
      cancer. CONCLUSION: Bovie injury to the bowel has a hidden depth, causing a slow
      transmural tissue necrosis, and it might also impair local healing and eventually
      lead to perforation. Thus, the patient may present later than the usual period
      for wound healing and remodeling as previously reported. Given the disastrous
      consequence, it is imperative to perform a good surgical repair of even a minor
      Bovie injury to the bowel. This is the first report of a delayed presentation (>1
      month) of a Bovie injury of the bowel.

PMID- 24018097
TI  - Emergency laparoscopic ileocecal resection for Crohn's acute obstruction.
AB  - INTRODUCTION: Emergency surgery for Crohn's disease (CD) is a rare entity, and
      its indications are scant in the published literature. Emergency laparoscopy for
      small bowel obstruction has gained wide dissemination with the spread of advanced
      laparoscopic skills within surgical practice. Therefore, incidental terminal
      ileitis after exploration might be a more-common finding in the near future, and
      further studies are needed to better ascertain proper surgical treatment. CASE
      DESCRIPTION: We report on a case of acute obstruction caused by undiagnosed
      terminal ileitis associated with CD. DISCUSSION AND CONCLUSION: The patient
      underwent explorative laparoscopy and subsequent video-assisted ileocecal
      resection with an optimal outcome.

PMID- 24018098
TI  - Own-age and own-sex biases in recognition of aged faces.
AB  - It is surprising how easily we are able to recognize people whom we have not seen
      in many years, somehow compensating for the aging-related facial changes that
      occurred. We measured the limits of the ability to recognize faces across the
      lifespan by young versus old men and women. Images of five males and five females
      at young and middle ages were morphed in 10% increments to create aged face
      images across the lifespan. Fifty-eight participants (28 females) judged whether
      pairs of photographs were of the same or different identity. Women outperformed
      men for female faces, exhibiting a sex difference and own-sex bias. Additionally,
      older participants showed an own-age bias and outperformed their younger
      counterparts with older stimuli. It appears that the recognition of faces is
      affected by the own-age and own-sex biases, potentially allowing us to remember
      some people better than others, thus mediating our interaction with the world. 

PMID- 24018099
TI  - Is the fluency of language outputs related to individual differences in
      intelligence and executive function?
AB  - There has been little research on the fluency of language production and
      individual difference variables, such as intelligence and executive function. In
      this study, we report data from 106 participants who completed a battery of
      standardized cognitive tasks and a sentence production task. For the sentence
      production task, participants were presented with two objects and a verb and
      their task was to formulate a sentence. Four types of disfluency were examined:
      filled pauses (e.g. uh, um), unfilled pauses, repetitions, and repairs.
      Repetitions occur when the speaker suspends articulation and then repeats the
      previous word/phrase, and repairs occur when the speaker suspends articulation
      and then starts over with a different word/phrase. Hierarchical structural
      equation modeling revealed a significant relationship between repair disfluencies
      and inhibition. Conclusions focus on the role of individual differences in
      cognitive ability and their role in models and theories of language production. 

PMID- 24018100
TI  - A new strategy for sequential assignment of intrinsically unstructured proteins
      based on 15N single isotope labelling.
AB  - We describe a new efficient strategy for the sequential assignment of amide
      resonances of a conventional (15)N-(1)H HSQC spectrum of intrinsically unfolded
      proteins, based on composite NOESY-TOCSY and TOCSY-NOESY mixing times. These
      composite mixing times lead to a Halpha-proton mediated unidirectional transfer
      of amide to amide proton. We have implemented the composite mixing times in an
      HSQC-NOESY-HSQC manner to obtain directional connectivity between amides of
      neighbouring residues. We experimentally determine the optimal mixing times for
      both transfer schemes, and demonstrate its use in the assignment for both a
      fragment of the neuronal tau protein and for alpha-synuclein. 

PMID- 24018101
TI  - Novel drugs for treating angina.

PMID- 24018102
TI  - Clinical, psychological and environmental predictors of prospective suicide
      events in patients with Bipolar Disorder.
AB  - Patients with Bipolar Disorder (BD) have high rates of suicide compared to the
      general population. The present study investigates the predictive power of
      baseline clinical, psychological and environmental characteristics as risk
      factors of prospective suicide events (attempts and completions). Data was
      collected from the Systematic Treatment Enhancement Program for Bipolar Disorder
      (STEP-BD) study. 3083 bipolar patients were included in this report, among these
      140 (4.6%) had a suicide event (8 died by suicide and 132 attempted suicide).
      Evaluation and assessment forms were used to collect clinical, psychological and
      socio-demographic information. Chi-square and independent t-tests were used to
      evaluate baseline characteristics. Potential prospective predictors were selected
      on the basis of prior literature and using a screening analysis of all risk
      factors that were associated with a history of suicide attempt at baseline and
      were tested using a Cox regression analysis. The strongest predictor of a suicide
      event was a history of suicide attempt (hazard ratio = 2.60, p-value < 0.001) in
      line with prior literature. Additional predictors were: younger age, a high total
      score on the personality disorder questionnaire and a high percentage of days
      spent depressed in the year prior to study entry. In conclusion, the present
      findings may help clinicians to identify patients at high risk for suicidal
      behavior upon presentation for treatment.

PMID- 24018103
TI  - Association study of the vesicular monoamine transporter gene SLC18A2 with
      tardive dyskinesia.
AB  - Tardive dyskinesia (TD) is an involuntary movement disorder that can occur in up
      to 25% of patients receiving long-term first-generation antipsychotic treatment.
      Its etiology is unclear, but family studies suggest that genetic factors play an
      important role in contributing to risk for TD. The vesicular monoamine
      transporter 2 (VMAT2) is an interesting candidate for genetic studies of TD
      because it regulates the release of neurotransmitters implicated in TD, including
      dopamine, serotonin, and GABA. VMAT2 is also a target of tetrabenazine, a drug
      used in the treatment of hyperkinetic movement disorders, including TD. We
      examined nine single-nucleotide polymorphisms (SNPs) in the SLC18A2 gene that
      encodes VMAT2 for association with TD in our sample of chronic schizophrenia
      patients (n = 217). We found a number of SNPs to be nominally associated with TD
      occurrence and the Abnormal Involuntary Movement Scale (AIMS), including the
      rs2015586 marker which was previously found associated with TD in the CATIE
      sample (Tsai et al., 2010), as well as the rs363224 marker, with the low
      expression AA genotype appearing to be protective against TD (p = 0.005). We
      further found the rs363224 marker to interact with the putative functional D2
      receptor rs6277 (C957T) polymorphism (p = 0.001), supporting the dopamine
      hypothesis of TD. Pending further replication, VMAT2 may be considered a
      therapeutic target for the treatment and/or prevention of TD.

PMID- 24018104
TI  - Executive function performance is reduced during occupational burnout but can
      recover to the level of healthy controls.
AB  - BACKGROUND: Burnout is a work-related syndrome that comprises physical fatigue,
      emotional exhaustion and cognitive weariness and is considered to be a risk
      factor for the development of major depression. While cognitive impairments in
      major depression persist even after remission of mood symptoms, the role of
      cognitive impairments in burnout is less clear. The hypothesis tested in the
      present study submits that executive function performance is reduced during
      burnout compared to healthy subjects but can recover to normal levels. METHODS:
      12 male subjects (mean age 45.8 +/- 6.8 years) suffering from occupational
      burnout took part in the study. They completed questionnaires related to burnout
      severity and underwent testing of executive functions twice at baseline and at
      follow-up 12 weeks later. Between baseline and follow-up burnout participants
      performed regular aerobic exercise training. Executive function performance at
      baseline and follow-up was compared to 12 matched healthy controls. RESULTS:
      Executive functioning was significantly reduced during acute burnout compared to
      healthy controls. At follow-up, both burnout severity and executive functioning
      were improved. Changes in burnout severity and executive function performance
      were not related. CONCLUSIONS: Data suggest that executive function performance
      is impaired during acute burnout but can recover to the level of healthy
      controls. This finding is at odds with the finding of persistent deficits in the
      same tests found in major depression even after remission of depressive mood.
      Results may indicate that the pathophysiological changes underlying the impaired
      executive functioning during burnout are less pronounced compared to those in
      major depression.

PMID- 24018105
TI  - Collagen microsphere serving as a cell carrier supports oligodendrocyte
      progenitor cell growth and differentiation for neurite myelination in vitro.
AB  - INTRODUCTION: Microspheres fabricated from natural materials serve as a promising
      biodegradable and biocompatible carrier in a small volume for efficient cell
      delivery to the lesion of the injured neural tissue to generate biological
      functions. As the major component of extracellular matrix and due to its natural
      abundance within the body, collagen may be fabricated into microspheres and
      improve the ability of pre-seeded cells on the microspheres to encounter the
      hostile micro-environment in the lesion. METHODS: In this study, collagen
      microspheres were fabricated using the water-in-oil emulsion technique and cross
      linked with 1-ethyl-3-(3-dimethylaminopropryl) carbodiimide. Oligodendrocyte
      progenitor cells isolated from postnatal day P1 to 2 rats were cultured and
      differentiated on the microspheres. The microspheres carrying the oligodendrocyte
      progenitor cells were co-cultured with dorsal root ganglions from 15-day-old rat
      embryos. The myelination formation was studied for the co-culture of
      oligodendrocyte progenitor cells and dorsal root ganglions. RESULTS: We showed
      that the viability of oligodendrocyte progenitor cells, B104 cells and PC12 cells
      grown on microspheres was not significantly different with those in cell culture
      plates. Oligodendrocyte progenitor cells differentiated into oligodendrocytes on
      collagen microspheres. The oligodendrocytes grown on microspheres extended
      processes that wrapped the axons of dorsal root ganglion neurons and the
      formation of myelin sheath was observed in the co-culture. CONCLUSIONS: This
      study demonstrates the feasibility of collagen microspheres in further
      applications for the delivery of neural progenitor cells for neural regeneration.

PMID- 24018106
TI  - Sedation for paediatric transcatheter atrial septal defect closure: comparison of
      two sedation protocols.
AB  - AIM: This study aimed to compare the effects of dexmedetomidine-propofol and
      ketamine-propofol sedation on haemodynamic stability, immobility, and recovery
      time in children who underwent transcatheter closure of atrial septal defects.
      METHODS: In all, 46 children scheduled for transcatheter closure of atrial septal
      defects (n = 46) were included. The dexmedetomidine-propofol group (n = 23)
      received dexmedetomidine (1 MUg/kg) and propofol (1 mg/kg) for induction,
      followed by dexmedetomidine (0.5 MUg/kg/hour) and propofol (100 MUg/kg/minute)
      for maintenance. The ketamine-propofol group (n = 23) received ketamine (1 mg/kg)
      and propofol (1 mg/kg) for induction, followed by ketamine (1 mg/kg) and propofol
      (100 MUg/kg/minute) for maintenance. RESULTS: In all, 11 patients in the
      dexmedetomidine group (47.8%) and one patient (4.3%) in the ketamine group
      demonstrated a decrease >=20% from the baseline in mean arterial pressure (p =
      0.01). Heart rates decreased >=20% from the baseline value in 10 patients (43.4%)
      in the dexmedetomidine group and three patients (13%) in the ketamine group (p =
      0.047). Heart rate values were observed to be lower in the dexmedetomidine group
      throughout the procedure after the first 10 minutes. The number of patients
      requiring additional propofol was higher in the dexmedetomidine group (p = 0.01).
      The recovery times were similar in the two groups--15.86 +/- 6.50 minutes in the
      dexmedetomidine group and 19.65 +/- 8.19 minutes in the ketamine group; p = 0.09.
      CONCLUSION: The ketamine-propofol combination was less likely to induce
      haemodynamic instability, with no significant change in recovery times, compared
      with the dexmedetomidine-propofol combination. The ketamine-propofol combination
      provided good conditions for the intervention.

PMID- 24018107
TI  - Increase of club cell (Clara) protein (CC16) in plasma and urine after exercise
      challenge in asthmatics and healthy controls, and correlations to exhaled breath
      temperature and exhaled nitric oxide.
AB  - Exercise is known to affect the airway epithelium through dehydration, followed
      by a release of mediators, such as club cell (Clara) protein (CC16). The aim of
      this study was to follow the CC16 levels at repeated time points in plasma and
      urine after exercise in asthmatic subjects and controls, and to relate the
      findings to exhaled breath temperature (EBT) and exhaled nitric oxide (NO).
      Twenty-two asthmatics and 18 healthy subjects performed an exercise challenge
      test on a treadmill. Lung function, CC16 in plasma and urine, EBT and fractional
      exhaled NO were investigated before and repeatedly for 60 min after the exercise.
      The increase in CC16 concentration in plasma was seen already one minute after
      exercise (p < 0.001) and increased further after 20 (p = 0.009) until 60 min (p =
      0.001). An increase in urinary levels of CC16 peaked after 30 min (p < 0.001),
      and declined after 60 min but were still higher than baseline (p = 0.002). There
      were no differences in plasma or urine CC16 levels between asthmatics and
      controls, but males had higher plasma levels compared to females (p < 0.001) at
      all time points. EBT peaked at 15 min (p < 0.001) and thereafter declined, and
      FENO50 (p < 0.0001), alveolar NO concentration (p = 0.049) and bronchial flux of
      NO (p = 0.0055) decreased after exercise. In conclusion, this study shows that
      CC16 in plasma increased during 60 min after exercise, not synchronized with CC16
      levels in urine. CC16 levels in plasma correlated to EBT and exhaled NO,
      reflecting an overall epithelial involvement. There was no difference between
      asthmatics and healthy controls, showing a physiological rather than
      pathophysiological response. 

PMID- 24018108
TI  - Generic process for highly stable metallic nanoparticle-semiconductor
      heterostructures via click chemistry for electro/photocatalytic applications.
AB  - Metallic nanoparticles (MNP) are utilized as electrocatalysts, cocatalysts, and
      photon absorbers in heterostructures that harvest solar energy. In such systems,
      the interface formed should be stable over a wide range of pH values and
      electrolytes. Many current nonthermal processing strategies rely on physical
      interactions to bind the MNP to the semiconductor. In this work, we demonstrate a
      generic chemical approach for fabricating highly stable
      electrochemically/photocatalytically active monolayers and tailored multilayered
      nanoparticle structures using azide/alkyne-modified Au, TiO2, and SiO2
      nanoparticles on alkyne/azide-modified silicon, indium tin oxide, titania,
      stainless steel, and glass substrates via click chemistry. The stability,
      electrical, electrochemical, and photocatalytic properties of the interface are
      shown via electrochemical water splitting, methanol oxidation, and photocatalytic
      degradation of Rhodamine B (RhB) dye. The results suggest that the proposed
      approach can be extended for the large-scale fabrication of highly stable
      heterostructure materials for electrochemical and photoelectrocatalytic devices. 

PMID- 24018109
TI  - Activation of cAMP-response element-binding protein is positively regulated by
      PKA and calcium-sensitive calcineurin and negatively by PKC in insect.
AB  - The cAMP response element binding protein, CREB, is a G protein-coupled receptor
      (GPCR) signal-activated transcription factor implicated in the control of many
      biological processes. In the current study, we constructed a cAMP response
      element (CRE)-driven luciferase assay system for GPCR characterization in insect
      cells. Our results indicated that Gs-coupled Bombyx adipokinetic hormone receptor
      (AKHR) and corazonin receptor could effectively initiate CRE-driven luciferase
      transcription, but forskolin, a reagent widely used to activate adenylyl cyclase
      in mammalian systems, failed to induce luciferase activity in insect cells co
      transfected with a CRE-driven reporter construct upon agonist treatment. Further
      investigation revealed that the specific protein kinase C (PKC) inhibitors
      exhibited stimulatory effects on CRE-driven reporter transcription, and blockage
      of Ca(2+) signals and inhibition of Ca(2+)-dependent calcineurin resulted in a
      significant decrease in the luciferase activity. Taken together, these results
      suggest that PKC likely acts as a negative regulator to modulate CREB activation;
      in contrast, Ca(2+) signals and Ca(2+)-dependent calcineurin, in addition to PKA,
      essentially contribute to the positive regulation of CREB activity. This study
      presents evidence to elucidate the underlying molecular mechanism by which CREB
      activation is regulated in insects. 

PMID- 24018110
TI  - Comment on the paper "Effect of statin treatment on adrenomyeloneuropathy with
      cerebral inflammation: a revisit".

PMID- 24018111
TI  - Response to: timing of the sentinel lymph node biopsy in breast cancer patients
      receiving neoadjuvant therapy - recommendations for clinical guidance.

PMID- 24018112
TI  - Evaluating the impact of nutrition programs on psychosocial health.

PMID- 24018113
TI  - Am I a social, evasive, or educating parent?

PMID- 24018114
TI  - Revisiting the paradigm of myostatin in vertebrates: insights from fishes.
AB  - In the last decade, myostatin (MSTN), a member of the TGFbeta superfamily, has
      emerged as a strong inhibitor of muscle growth in mammals. In fish many studies
      reveal a strong conservation of mstn gene organization, sequence, and protein
      structures. Because of ancient genome duplication, teleostei may have retained
      two copies of mstn genes and even up to four copies in salmonids due to
      additional genome duplication event. In sharp contrast to mammals, the different
      fish mstn orthologs are widely expressed with a tissue-specific expression
      pattern. Quantification of mstn mRNA in fish under different physiological
      conditions, demonstrates that endogenous expression of mstn paralogs is rarely
      related to fish muscle growth rate. In addition, attempts to inhibit MSTN
      activity did not consistently enhance muscle growth as in mammals. In vitro, MSTN
      stimulates myotube atrophy and inhibits proliferation but not differentiation of
      myogenic cells as in mammals. In conclusion, given the strong mstn expression non
      muscle tissues of fish, we propose a new hypothesis stating that fish MSTN
      functions as a general inhibitors of cell proliferation and cell growth to
      control tissue mass but is not specialized into a strong muscle regulator. 

PMID- 24018115
TI  - High water temperature impairs ovarian activity and gene expression in the brain
      pituitary-gonadal axis in female red seabream during the spawning season.
AB  - Temperature plays a pivotal role in the control of seasonal reproduction in
      temperate fish species. It is well known that temperatures that exceed a certain
      threshold impair gonadal development, maturation, and spawning. However, the
      endocrine mechanisms that underlie these effects are poorly understood. We
      evaluated the effect of high water temperature on the brain-pituitary-gonadal (B
      P-G) axis of a perciform fish, red seabream, Pagrus (Chrysophrys) major during
      its spawning season (April-May). Fish were reared at either high (24  degrees C:
      H-group) or optimal/control (17  degrees C: C-group) temperatures for 5 or 10 d.
      After 5 d, the transcript abundance of gonadotropin-releasing hormone-1 (GnRH1)
      in the brain and GnRH receptor (GnRH-R) and FSH-beta in the pituitary were
      significantly lower in H-group than in C-group. Conversely, there was no
      difference in pituitary LH-beta mRNA levels, serum concentrations of estradiol
      17beta (E2), or the gonadosomatic index (GSIs) between H- and C-groups on Day 5.
      After 10 d, the ovaries of all H-group fish had completely regressed and were
      filled with only perinucleolar stage primary oocytes and atretic oocytes. The
      brain GnRH1 expression, pituitary GnRH-R and pituitary LH-beta expression, serum
      E2 concentrations, and the GSI were significantly lower in the H-group on Day 10.
      Our results suggest that high water temperature is the proximate driver of the
      termination of the spawning season of female red seabream. The effect appears to
      be mediated by suppression of gene expression in the B-P-G axis.

PMID- 24018116
TI  - Greenhouse gas emissions during MSW landfilling in China: influence of waste
      characteristics and LFG treatment measures.
AB  - Reducing greenhouse gas (GHG) emissions from municipal solid waste (MSW)
      treatment can be highly cost-effective in terms of GHG mitigation. This study
      investigated GHG emissions during MSW landfilling in China under four existing
      scenarios and in terms of seven different categories: waste collection and
      transportation, landfill management, leachate treatment, fugitive CH4 (FM)
      emissions, substitution of electricity production, carbon sequestration and N2O
      and CO emissions. GHG emissions from simple sanitary landfilling technology where
      no landfill gas (LFG) extraction took place (Scenario 1) were higher (641-998 kg
      CO2-eq.t(-1)ww) than those from open dump (Scenario 0, 480-734 kg CO2-eq.t(
      1)ww). This was due to the strictly anaerobic conditions in Scenario 1. LFG
      collection and treatment reduced GHG emissions to 448-684 kg CO2-eq.t(-1)ww in
      Scenario 2 (with LFG flare) and 214-277 kg CO2-eq.t(-1)ww in Scenario 3 (using
      LFG for electricity production). Amongst the seven categories, FM was the
      predominant contributor to GHG emissions. Global sensitivity analysis
      demonstrated that the parameters associated with waste characteristics (i.e. CH4
      potential and carbon sequestered faction) and LFG management (i.e. LFG collection
      efficiency and CH4 oxidation efficiency) were of great importance. A further
      learning on the MSW in China indicated that water content and dry matter content
      of food waste were the basic factors affecting GHG emissions. Source separation
      of food waste, as well as increasing the incineration ratio of mixed collected
      MSW, could effectively mitigate the overall GHG emissions from landfilling in a
      specific city. To increase the LFG collection and CH4 oxidation efficiencies
      could considerably reduce GHG emissions on the landfill site level. While, the
      improvement in the LFG utilization measures had an insignificant impact as long
      as the LFG is recovered for energy generation. 

PMID- 24018117
TI  - An overview of photocatalysis phenomena applied to NOx abatement.
AB  - This review provides a short introduction to photocatalysis technology in terms
      of the present environmental remediation paradigm and, in particular, NOx
      photoabatement. The fundamentals of photoelectrochemical devices and the
      photocatalysis phenomena are reviewed, highlighting the main reaction mechanisms.
      The critical historical developments on heterogeneous photocatalysis are briefly
      discussed, giving particular emphasis to the pioneer works in this field. The
      third part of this work focus mainly on NOx removal technology considering topics
      such as: TiO2 photochemistry; effect of the operating conditions on the
      photocatalysis process; Langmuir-Hinshelwood modeling; TiO2 photocatalytic
      immobilization approaches; and their applications. The last section of the paper
      presents the main conclusions and perspectives on the opportunities related to
      this technology. 

PMID- 24018118
TI  - A methodological approach to understand functional relationships between
      ecological indices and human-induced pressures: the case of the Posidonia
      oceanica meadows.
AB  - The European Water Framework Directive (WFD) 2000/60/EC requests the achievement
      of the Good Status for all surface waters, including the coastal waters, by 2015.
      In order to check compliance with the needs of Directive, Italian national
      monitoring data on Posidonia oceanica meadows have been explored and the
      relationships among the Posidonia Rapid and Easy Index (PREI), and human-induced
      pressures have been analyzed along the Italian coasts. The aim of this work is to
      establish functional relationships between a response variable (i.e. the PREI)
      and a set of potential pressure (i.e. land use, potential organic and nutrient
      loading, pesticides) and status (i.e. transparency, trophic level and stability
      of the water column) indicators in a quantitative way. The ecological responses
      of coastal marine environment have been evaluated using appropriate statistical
      tools, such as the multiple linear regression analyses and "linear programming"
      techniques. Results show that more than 70% of the variability of the P. oceanica
      meadows status, expressed as PREI value, is significantly explained only by a few
      pressure/status indicators (namely: potential organic load, specific nitrogen
      load, natural areas extent, water column transparency), among all those initially
      considered in the model. The application of the proposed model could allow
      decision makers to better address remedial actions and to achieve the
      environmental targets proposed by the EU Directives. 

PMID- 24018119
TI  - Dynamic mathematical models for biodegradation of formaldehyde by Ralstonia
      eutropha in a batch bioreactor.
AB  - Degradation of formaldehyde by Ralstonia eutropha was studied in a batch
      bioreactor operated in recycling mode (30  degrees C, initial pH of 6.5, aeration
      rate 0.5 vvm, and a recycling flow rate of 6 mL min(-1)). Growth kinetics
      equations were described using four substrate inhibition models, and the initial
      formaldehyde concentration ranged from 54.5 to 993.0 mg L(-1). In each case,
      model parameters were estimated interactively using nonlinear regression analysis
      and on the basis of the goodness of fit, the fitness of the model to the
      experimental data was obtained (i.e., the coefficient of determination and the
      percent of standard deviation). The estimated parameters according to the Luong
      equation were MUmax = 0.101 h(-1), KS = 54.1 mg L(-1), Sm = 1329 mg L(-1), and n
      = 2.07. According to the maintenance energies explained by Pirt, cell maintenance
      was quantified with q = AMU + B; where A and B are the associated and non
      associated growth parts of substrate consumption, respectively. The importance of
      these terms was verified using the developed models, which would efficiently
      describe the dynamic nature of growth and formaldehyde biodegradation. 

PMID- 24018120
TI  - Accuracy of surface tension measurement from drop shapes: the role of image
      analysis.
AB  - Axisymmetric Drop Shape Analysis (ADSA) has been extensively used for surface
      tension measurement. In essence, ADSA works by matching a theoretical profile of
      the drop to the extracted experimental profile, taking surface tension as an
      adjustable parameter. Of the three main building blocks of ADSA, i.e. edge
      detection, the numerical integration of the Laplace equation for generating
      theoretical curves and the optimization procedure, only edge detection (that
      extracts the drop profile line from the drop image) needs extensive study. For
      the purpose of this article, the numerical integration of the Laplace equation
      for generating theoretical curves and the optimization procedure will only
      require a minor effort. It is the aim of this paper to investigate how far the
      surface tension accuracy of drop shape techniques can be pushed by fine tuning
      and optimizing edge detection strategies for a given drop image. Two different
      aspects of edge detection are pursued here: sub-pixel resolution and pixel
      resolution. The effect of two sub-pixel resolution strategies, i.e. spline and
      sigmoid, on the accuracy of surface tension measurement is investigated. It is
      found that the number of pixel points in the fitting procedure of the sub-pixel
      resolution techniques is crucial, and its value should be determined based on the
      contrast of the image, i.e. the gray level difference between the drop and the
      background. On the pixel resolution side, two suitable and reliable edge
      detectors, i.e. Canny and SUSAN, are explored, and the effect of user-specified
      parameters of the edge detector on the accuracy of surface tension measurement is
      scrutinized. Based on the contrast of the image, an optimum value of the user
      specified parameter of the edge detector, SUSAN, is suggested. Overall, an
      accuracy of 0.01mJ/m(2) is achievable for the surface tension determination by
      careful fine tuning of edge detection algorithms. 

PMID- 24018121
TI  - Novel GCH-1 mutations and unusual long-lasting dyskinesias in Korean families
      with dopa-responsive dystonia.
AB  - OBJECTIVE: To describe the long-term follow-up data of Korean patients with GTP
      cyclohydrolase (GTPCH) I deficient dopa-responsive dystonia (DRD) with novel
      mutations and unusual long-lasting dyskinesias. METHODS: Clinical features and
      genetic testing results of GCH1 from 19 patients that included 4 families who
      have been followed-up for up to 25 years were analyzed. RESULTS: GCH1 mutations
      were confirmed in all our symptomatic subjects including 3 novel point mutations.
      All the subjects except for one family had typical manifestations of autosomal
      dominant GTPCH-I deficient DRD including early childhood onset dystonia
      predominantly in the legs, marked diurnal variation, intact cognition, no other
      systemic symptoms, and excellent sustained response to levodopa. The one family
      who was the exception had two gene positive members of DRD and one with dopa
      unresponsive cervical dystonia with negative GCH1 mutation. One family and a
      sporadic case had been reported as gene negative in a previous study, but they
      typically had preserved dopamine transporter binding and low neopterin levels in
      cerebrospinal fluids; thus, GCH-1 mutation had been highly suspected, which was
      now confirmed by repeating the genetic testing this time. An early childhood
      onset patient developed choreiform dyskinesias right after administration of
      levodopa. The dyskinesia had lasted for more than 4 years regardless of the
      levodopa dosages and then subsided while maintaining levodopa. CONCLUSION: This
      report emphasizes the usefulness of the neopterin level in cerebrospinal fluids
      and dopamine transporter imaging in the differential diagnosis of DRD syndromes
      and a possible mechanism of levodopa-induced-dyskinesia in early childhood onset
      case.

PMID- 24018122
TI  - Radiofrequency heating and magnetic field interactions of fixed partial dentures
      during 3-tesla magnetic resonance imaging.
AB  - OBJECTIVE: This study evaluated the heating and magnetic field interactions of
      fixed partial dentures in a 3-Tesla (3T) magnetic resonance imaging (MRI)
      environment. STUDY DESIGN: Three substructure materials (Co-Cr, Ni-Cr, ZrO2) were
      used to fabricate twelve 4-retained bridges and 12 crowns. Specimens were
      evaluated at 3T for radiofrequency heating and magnetic field interactions. One
      way analysis of variance (ANOVA) test was used to compare continuous variables of
      temperature change. Significance was set at P < .05. Translational attraction and
      torque values of specimens were also evaluated. RESULTS: None of the groups
      exhibited excessive heating (mean temperature change, < 1.4  degrees C), with
      maximum increase at the end of the T-1. Moreover, in all groups, only relatively
      minor magnetic field interactions that would not cause movement in situ were
      observed. CONCLUSION: The study findings indicated that patients with fixed
      partial dentures (single crown or bridge) fabricated from Co-Cr, Ni-Cr, and
      zirconia substructures may safely undergo MRI at up to 3T.

PMID- 24018123
TI  - In reply.

PMID- 24018124
TI  - Comparison of cone-beam computed tomography with intraoral photostimulable
      phosphor imaging plate for diagnosis of endodontic complications: a simulation
      study.

PMID- 24018125
TI  - Tissue microarray analysis reveals the expression and prognostic significance of
      phosphorylated AktThr308 in oral squamous cell carcinoma.
AB  - OBJECTIVES: We aimed to investigate the association between the expression of
      phosphorylated Akt(Thr308) (p-Akt(Thr308)) in oral squamous cell carcinoma (OSCC)
      tissues and clinicopathological parameters of OSCC patients and to verify the
      validity of p-Akt(Thr308) as a prognostic biomarker. STUDY DESIGN: One hundred
      and ninety-one patients with OSCC were recruited for the study. We tested the
      expression of p-Akt(Thr308) by immunohistochemistry (IHC) with tissue microarray
      (TMA) and analyzed with digital pathology analysis software. The
      clinicopathological parameters of all patients were collected from follow-up.
      RESULTS: P-Akt(Thr308) was detected in 95.2% of OSCC patients. The expression of
      p-Akt(Thr308) was significantly correlated with local recurrence and five-year
      survival rate. High expression of p-Akt(Thr308) in OSCC was associated with poor
      prognosis. CONCLUSION: P-Akt(Thr308) might be a candidate biomarker for the
      prediction of OSCC prognosis.

PMID- 24018126
TI  - Root malformation associated with a cervical mineralized diaphragm--a distinct
      form of tooth abnormality?
AB  - OBJECTIVE: Deviations in length and shape of tooth roots result from hard tissue
      resorption or occur as a developmental disorder. The purpose of this report is to
      present a type of root malformation which seems to have gone unreported so far.
      STUDY DESIGN: Two patients showing severely dysplastic roots of all permanent
      first molars were evaluated using radiography, histology as well as scanning and
      transmission electron microscopy. RESULTS: Medical histories of the patients
      revealed significant, but diverse events in the first year after birth.
      Radiographically the pulp cavity floors of the affected molars in large part were
      occupied by ectopic mineralized plates. Microscopically these plates consisted of
      hard tissue, densely calcified globules, and a network of canals which contained
      large blood vessels and were lined by cementum and periodontal ligament.
      CONCLUSIONS: We propose that the ectopic mineralized plate was derived from the
      dental follicle, had developed during crown formation around the vascular plexus
      at the base of the dental papilla, and represented a mechanical obstacle
      interfering with normal root development.

PMID- 24018127
TI  - Enhancement cone beam computed tomography filters improve in vitro periimplant
      dehiscence detection.
AB  - OBJECTIVE: To investigate whether cone beam computed tomography filters would
      improve periimplant dehiscence detection. STUDY DESIGN: A hundred titanium
      implants were placed in bovine ribs in which defects simulating periimplant
      dehiscence had previously been created. After images acquisition, three oral
      radiologists assessed them with and without the following filters: Angio Sharpen
      high 5 * 5, Shadow, Sharpen 3 * 3, Sharpen Mild, and Smooth. The McNemar test
      verified the disagreement between all images versus the reference standard and
      original images versus images with filters; P < .05 was considered statistically
      significant. RESULTS: Dehiscence detection using the original images and the
      Shadow filter disagreed from the reference standard (P < .05), as well as when
      using the filters instead of the original images (P < .05). CONCLUSION: All the
      filters tested, with the exception of the Shadow, improved periimplant dehiscence
      detection. The Sharpen 3 * 3 filter was considered best for this task.

PMID- 24018128
TI  - Analyzing differences between patient and proxy on Patient Reported Outcomes in
      multiple sclerosis.
AB  - BACKGROUND: Proxy respondents, partners of multiple sclerosis (MS) patients, can
      provide valuable information on the MS patients' disease. In an earlier
      publication we found relatively good agreement on patient reported outcomes
      (PROs) measuring physical impact and functioning, but we found large differences
      on (neuro)psychological scales. OBJECTIVE: We aim to identify patient and proxy
      related variables explaining differences between patients' and proxies' ratings
      on five PROs. METHODS: We report on data from 175 MS patients and proxy
      respondents. Regression analyses were performed, using as dependent variable the
      mean differences on five scales: Physical and Psychological scale of the Multiple
      Sclerosis Impact Scale (MSIS-29), the Multiple Sclerosis Walking Scale (MSWS),
      Guy's Neurological Disability Scale (GNDS) and the Multiple Sclerosis
      Neuropsychological Screening Questionnaire (MSNQ). The independent variables were
      patient, proxy and disease related variables. RESULTS: Caregiver strain was
      significantly related to differences between patient and proxy scores for all
      five PROs. A higher level of patient anxiety on the HADS was linked to larger
      differences on all PROs except the GNDS. In addition, cognitive functioning,
      proxy depression, walking ability, proxy gender and MS related disability were
      contributing to the discrepancies. CONCLUSION: We found several patient and proxy
      factors that may contribute to discrepancies between patient and proxy scores on
      MS PROs. The most important factor is caregiver burden.

PMID- 24018129
TI  - Paraneoplastic cerebellar degeneration associated with an onconeural antibody
      against creatine kinase, brain-type.
AB  - Onconeural immunity, a cancer-stimulated immune reaction that cross-reacts with
      neural tissues, is considered to be the principal pathological mechanism for
      paraneoplastic neurological syndromes (PNS). A common PNS is paraneoplastic
      cerebellar degeneration (PCD). We had encountered a PCD patient with urothelial
      carcinomas (UC) of the urinary bladder who was negative for the well
      characterized PNS-related onconeural antibodies. In the present study, we aimed
      to identify a new PCD-related onconeural antibody, capable of recognizing both
      cerebellar neurons and cancer tissues from the patient, and applied a proteomic
      approach using mass spectrometry. We identified anti-creatine kinase, brain-type
      (CKB) antibody as a new autoantibody in the serum and cerebrospinal fluid from
      the patient. Immunohistochemistry indicated that anti-CKB antibody reacted with
      both cerebellar neurons and UC of the urinary bladder tissues. However, anti-CKB
      antibody was not detected in sera from over 30 donors, including bladder cancer
      patients without PCD, indicating that anti-CKB antibody is required for onset of
      PCD. We also detected anti-CKB antibody in sera from three other PCD patients.
      Our study demonstrated that anti-CKB antibody may be added to the list of PCD
      related autoantibodies and may be useful for diagnosis of PCD. 

PMID- 24018130
TI  - Modeling iron-catecholates binding to NGAL protein.
AB  - Neutrophil gelatinase associated lipocalin (NGAL) protein is attracting a great
      interest because of its antibacterial properties played upon modulating iron
      content in competition against iron acquisition processes developed by pathogenic
      bacteria that bind selective ferric iron chelators (siderophores). Besides its
      known high affinity to enterobactin, the most important siderophore, it has been
      recently shown that NGAL is able to bind Fe(III) coordinated by catechols. The
      selective binding of Fe(III)-catechol ligands to NGAL is here studied by using
      iron coordination structures with one, two, and three catecholate ligands. By
      means of a computational approach that consists of B3LYP/6-311G(d,p) quantum
      calculations for geometries, electron properties and electrostatic potentials of
      ligands, protein-ligand flexible docking calculations, analyses of protein-ligand
      interfaces, and Poisson-Boltzmann electrostatic potentials for proteins, we study
      the binding of iron catecholate ligands to NGAL as a central member of the
      lipocalin family of proteins. This approach provides a modeling basis for
      exploring in silico the selective binding of iron catecholates ligands giving a
      detailed picture of their interactions in terms of electrostatic effects and a
      network of hydrogen bonds in the protein binding pocket. 

PMID- 24018131
TI  - Tissue, cell and engineering.

PMID- 24018132
TI  - Solution-processed MoS(x) as an efficient anode buffer layer in organic solar
      cells.
AB  - We reported a facile solution-processed method to fabricate a MoSx anode buffer
      layer through thermal decomposition of (NH4)2MoS4. Organic solar cells (OSCs)
      based on in situ growth MoSx as the anode buffer layer showed impressive
      improvements, and the power conversion efficiency was higher than that of
      conventional PEDOT:PSS-based device. The MoSx films obtained at different
      temperatures and the corresponding device performance were systematically
      studied. The results indicated that both MoS3 and MoS2 were beneficial to the
      device performance. MoS3 could result in higher Voc, while MoS2 could lead to
      higher Jsc. Our results proved that, apart from MoO3, molybdenum sulfides and
      Mo(4+) were also promising candidates for the anode buffer materials in OSCs. 

PMID- 24018133
TI  - BASHH's patient leaflets are produced through close collaboration between experts
      and patients.

PMID- 24018134
TI  - Response--letter to the editor regarding prevalence of hypertension in Portuguese
      adolescents.

PMID- 24018135
TI  - Long-term survival in a patient with single ventricle.

PMID- 24018136
TI  - Different recycle behavior of Cu2+ and Fe3+ ions for phenol photodegradation over
      TiO2 and WO3.
AB  - Photocatalytic degradation of organic pollutants on TiO2 and WO3 have been widely
      studied, but the effects of Cu(2+) and Fe(3+) ions still remain unclear. In this
      work, we have found that the recycle behavior of Cu(2+) and Fe(3+) are greatly
      dependent on the photocatalytic activity of metal oxide used. With TiO2 (P25,
      anatase, and rutile), all the time profiles of phenol degradation in water under
      UV light well fitted to the apparent first-order rate equation. On the addition
      of Cu(2+), phenol degradation on anatase, rutile and WO3 also followed the first
      order kinetics. On the addition of Fe(3+), the initial rate of phenol degradation
      on each oxide was increased, but only the reactions on three TiO2 became to
      follow the first order kinetics after half an hour. The relevant rate constants
      for phenol degradation in the presence of Cu(2+) or Fe(3+) were larger than those
      in the absence of metal ions. Under visible light, phenol degradation on WO3 was
      also accelerated on the addition of Fe(3+) or Cu(2+). Moreover, several
      influencing factors were examined, including the metal ion photolysis in
      solution. It becomes clear that as electron scavengers of TiO2 and WO3, Fe(3+) is
      better than Cu(2+), while they are better than O2. We propose that Fe(3+) recycle
      occurs through H2O2, photogenerated from TiO2, not from WO3, while Cu(2+)
      regeneration on a moderate photocatalyst is through the dissolved O2 in water. 

PMID- 24018137
TI  - Degradation characteristics of 2,4-dichlorophenoxyacetic acid in electro
      biological system.
AB  - The reductive degradation of 2,4-dichlorophenoxyacetic acid (2,4-D) was studied
      in an electro-biological system, a biological system and an electric catalytic
      system, respectively. Electrochemical characteristics were monitored by cyclic
      voltammetry and the intermediate products of 2,4-D degradation were determined by
      high speed liquid chromatography (HPLC). The results showed that all 2,4-D
      degradations in the three systems conformed to the kinetics characteristics of
      one-order reaction, and the degradation kinetics constants were 28.74 * 10(-2) h(
      1), 19.73 * 10(-2) h(-1) and 3.54 * 10(-2) h(-1), respectively. The kinetics
      constant in the electro-biological system was higher than the sum in the other
      two systems by 19%. The electrochemical assistance provided the electrons and
      accelerated the electron transfer rate in the microbial degradation of 2,4-D. The
      degradation resulted from the microbial reduction strengthened by the
      electrochemical assistance. The electron transfer existed between the electrode,
      cytochrome, NAD and the pollutants. A long-range electron transfer process could
      be achieved on the multi-phase interfaces between the electrode, bacteria and the
      pollutants.

PMID- 24018138
TI  - Do testosterone declines during the transition to marriage and fatherhood relate
      to men's sexual behavior? Evidence from the Philippines.
AB  - Testosterone (T) is thought to help facilitate trade-offs between mating and
      parenting in humans. Across diverse cultural settings married men and fathers
      have lower T than other men and couples' sexual activity often declines during
      the first years of marriage and after having children. It is unknown whether
      these behavioral and hormonal changes are related. Here we use longitudinal data
      from a large study in the Philippines (n=433) to test this model. We show that
      among unmarried non-fathers at baseline (n=153; age: 21.5 +/- 0.3 years) who
      became newly married new fathers by follow-up (4.5 years later), those who
      experienced less pronounced longitudinal declines in T reported more frequent
      intercourse with their partners at follow-up (p<0.01) compared to men with larger
      declines in T. Controlling for duration of marriage, findings were similar for
      men transitioning from unmarried to married (without children) (p<0.05). Men who
      remained unmarried and childless throughout the study period did not show similar
      T-sexual activity outcomes. Among newly married new fathers, subjects who had
      frequent intercourse both before and after the transition to married fatherhood
      had more modest declines in T compared to peers who had less frequent sex
      (p<0.001). Our findings are generally consistent with theoretical expectations
      and cross-species empirical observations regarding the role of T in male life
      history trade-offs, particularly in species with bi-parental care, and add to
      evidence that T and sexual activity have bidirectional relationships in human
      males.

PMID- 24018139
TI  - Levetiracetam resistance: Synaptic signatures & corresponding promoter SNPs in
      epileptic hippocampi.
AB  - Pharmacoresistance to antiepileptic drugs (AEDs) is a major clinical problem in
      patients with mesial temporal lobe epilepsy (mTLE). Levetiracetam (LEV)
      represents a unique type of AED as its high-affinity binding site, the synaptic
      vesicle protein SV2A, is a component of the presynaptic release machinery. LEV
      often leads to full seizure control even in previously refractory patients.
      However, approximately 30% of LEV-treated mTLE patients do not show a significant
      response to LEV from the beginning of the pharmacotherapy and are therefore
      classified as a priori non-responders. This unexpected phenomenon prompted
      genetic studies, which failed to characterize responsible SV2A sequence
      alterations. Here, we followed a different approach to study the mechanisms of
      LEV pharmacoresistance by screening for mRNA signatures specifically expressed in
      LEV a priori non-responders in epileptic brain tissue and subsequent promoter
      analyses of highly altered transcripts. To this end, we have used our unique
      access to analyze hippocampal tissue from pharmacoresistant TLE patients who
      underwent epilepsy surgery for seizure control (n = 53) stratified according to a
      priori LEV responders versus patients with impaired LEV-response. Transcriptome
      (Illumina platform) and subsequent multimodal cluster analyses uncovered
      strikingly abundant synapse-associated molecule mRNA signatures in LEV a priori
      non-responders. Subsequent promoter characterization revealed accumulation of the
      single nucleotide polymorphism (SNP) rs9305614 G-allele in a priori non
      responders to correlate to abundant mRNAs of phosphatidylinositol N
      acetylglucosaminyltransferase (PIGP), i.e. a key component of the Wnt-signaling
      pathway. By luciferase assays, we observed significantly stronger activation by
      the LBP-1 transcription factor of the rs9305614 G-allele PIGP promoter. The
      present data suggest an abundance of transcripts encoding for key synaptic
      components in the hippocampi of LEV a priori non-responder mTLE patients, which
      for PIGP as proof of concept can be explained by a particular promoter variant.
      Our data argue for epigenetic factors predisposing for a priori LEV
      pharmacoresistance by transcriptional 'overexposure of targets'.

PMID- 24018140
TI  - Challenges of implementing task-shifting in contraceptive care--an experience in
      Quebec, Canada.

PMID- 24018141
TI  - Catheter ablation of idiopathic ventricular tachycardia in children using the
      EnSite NavX system with/without fluoroscopy.
AB  - OBJECTIVES: Curative therapy of idiopathic ventricular tachycardia remains a
      challenge in interventional electrophysiology. The aim of this study was to
      demonstrate the utility of an EnSite NavX system in the catheter ablation of
      idiopathic ventricular tachycardia in children. PATIENTS AND METHODS: In all, 17
      children with idiopathic ventricular tachycardia underwent electrophysiological
      studies using the EnSite NavX system guidance. RESULTS: The mean patient age was
      13 +/- 2.4 years (range: 7.8-17.9) and the mean patient weight was 52.3 +/- 11.9
      kg (range: 32-75). The origin of ventricular tachycardia was in the right
      ventricular outflow tract in nine patients, in the left ventricle in six, near
      the bundle of His/right bundle branch in one, and in the left aortic cusp in one.
      The mean procedure and fluoroscopy times were 169.3 +/- 43.2 minutes and 8 +/-
      10.8 minutes, respectively. No fluoroscopy was used in six patients. The mean
      radiation exposure was 33.1 +/- 56.4 mGy. Acute success was achieved in 14
      patients (82%). The focus of ventricular tachycardia was epicardial in two failed
      procedures. During a mean follow-up of 8.5 +/- 7.6 months, ventricular
      tachycardia recurred in three patients, two of whom underwent a second procedure.
      Except for one patient who developed transient right bundle branch block, no
      complications were seen. CONCLUSION: Catheter ablation of idiopathic ventricular
      tachycardia in children can be performed safely and effectively with low
      fluoroscopy exposure using the EnSite NavX system.

PMID- 24018142
TI  - UV-MALDI mass spectrometric quantitation of uracil based pesticides in fruit soft
      drinks along with matrix effects evaluation.
AB  - This study focused on the development of the accurate and precise quantitative
      method for the determination of pesticides bromacil (1), terbacil (2), lenacil
      (3), butafenacil (4) and flupropacil (5) in fruit based soft drinks. Three
      different types of drinks are bought from market; huddled orange fruit drink
      (100%) (I), red-oranges (II) and multivitamin drink containing strawberry,
      orange, banana and maracuja (III). Samples were analyzed "with" and "without"
      pulp utilizing LC-ESI (or APCI) MS/MS, HPLC-ESI-(or APCI)-MS/MS and UV-MALDI
      Orbitrap-MS methods. The effect of high complexity of the food matrix on the
      analysis was discussed. Study focuses on the advantages of the UV-MALDI-Orbitrap
      MS method compared to the traditionally involved GC alone or hybrid methods such
      as GC-MS and LC-MS/MS for quantification of pesticides in water and soft drinks.
      The developed method included the techniques performed for validation,
      calibration and standardization. The target pesticides are widely used for the
      treatment of citrus fruits and pineapples, but for soft drink products, there are
      still no clear regulations on pesticide residues limits. The matrix effects in
      the analysis of fruit drinks required implementation of the exact standard
      reference material corresponds to the variety of food matrices. This paper
      contributed to the broad analytical implementation of the UV-MALDI-Orbitrap-MS
      method in the quality control and assessment programs for monitoring of pesticide
      contamination in fruit based sodas. 

PMID- 24018143
TI  - Biomarkers of effects of hypoxia and oil-shale contaminated sediments in
      laboratory-exposed gibel carp (Carassius auratus gibelio).
AB  - In North-East Estonia, considerable amounts of toxicants (e.g. polycyclic
      aromatic hydrocarbons (PAHs), phenols, heavy metals) leach into water bodies
      through discharges from the oil-shale industry. In addition, natural and
      anthropogenic hypoxic events in water bodies affect the health of aquatic
      organisms. Here we report a study on the combined effects of contaminated
      sediment and hypoxia on the physiology of gibel carp (Carssius auratus gibelio).
      We conducted a laboratory exposure study that involved exposure to polluted
      sediments from oil-shale industries (River Purtse) and sediments from a
      relatively clean environment (River Selja), together with sediments spiked with
      PAHs. The oxygen content (saturation vs. hypoxia (< 2 mg/L)) was changed to
      reflect hypoxia. A multi-biomarker approach was chosen to enable the combined
      effects to be assessed comprehensively and integratively. We used HPLC to measure
      the PAH concentration in sediment and fish muscle, fixed wavelength fluorescence
      (FF) analyses to indicate the presence of PAH metabolites in fish bile, and
      nuclear abnormalities in erythrocytes as markers of geno- and cyto-toxicity; and
      we monitored the change in body condition and measured EROD activity to indicate
      CYP1A induction. High levels of PAH conjugates in fish bile were found in the
      group exposed to the Purtse River sediment under hypoxia. The results suggested
      that induction of the CYP1A gene was modulated by hypoxia as well as by heavy
      metals. We found a correlation between several erythrocyte abnormalities (8
      shaped nuclei and blebbed nuclei) and PAH metabolite content in fish. In
      conclusion, a measurable effect of pollution from the oil-shale industry on fish
      health parameters was clear under different oxygen levels.

PMID- 24018145
TI  - Plasmodium falciparum origin recognition complex subunit 1 (PfOrc1) functionally
      complements Deltasir3 mutant of Saccharomyces cerevisiae.
AB  - Telomere position effect efficiently controls silencing of subtelomeric var
      genes, which are involved in antigenic variation in human malaria parasite
      Plasmodium falciparum. Although, PfOrc1 has been found to be associated with
      PfSir2 in the silencing complex, its function in telomere silencing remained
      uncertain especially due to an apparent lack of BAH domain at its amino-terminal
      region. Here we report that PfOrc1 possesses a Sir3/Orc1 like silencing activity.
      Using yeast as a surrogate organism we have shown that PfOrc1 could complement
      yeast Sir3 activity during telomere silencing in a Sir2 dependent manner. By
      constructing a series of chimera between PfOrc1 and ScSir3 we have observed that
      the amino-terminal domain of PfOrc1 harbors silencing activity similar to that
      present in the amino-terminal domain of ScSir3. We further generated several
      amino-terminal deletion mutants to dissect out such silencing activity and found
      that the first seventy amino acids at the amino-terminal domain are dispensable
      for its activity. Thus our results strongly supports that PfOrc1 may have a role
      in telomere silencing in this parasite. This finding will help to decipher the
      mechanism of telomere position effect in P. falciparum. 

PMID- 24018146
TI  - Behavioural changes in the flour beetle Tribolium confusum infected with the
      spirurid nematode Protospirura muricola.
AB  - We examined changes to the behaviour of flour beetles, Tribolium confusum,
      infected with the rodent stomach worm, the spirurid Protospirura muricola, in the
      context of the 'Behavioural Manipulation Hypothesis'. Trobolium confusum infected
      with the third-stage infective larvae of P. muricola showed consistently altered
      patterns of behaviour. Relative to uninfected beetles, over a measured time
      period, beetles infected with P. muricola were likely to move over a shorter
      distance, when moving their speed of movement was slower, they were more likely
      to stay in the illuminated area of their environment, more likely to emerge from
      darkened areas into the illuminated areas, and their longevity was significantly
      shortened. The changes in behaviour, as reflected in effects on speed of
      movement, were only evident among beetles that actually harboured infective cysts
      and not among those carrying younger infections when the larvae within their
      haemocoels would have been at an earlier stage of development and not yet capable
      of infecting the definitive murine hosts. We discuss whether these changes would
      have made the beetles more susceptible to predation by rodents, and specifically
      by the omnivorous eastern spiny mouse, Acomys dimidiatus, the natural definitive
      host of this parasite in Egypt, from where the P. muricola isolate originated,
      and whether they support the Behavioural Manipulation Hypothesis or reflect
      parasite-induced pathology. 

PMID- 24018144
TI  - Efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in
      cognitive reserve.
AB  - Cognitive reserve (CR) is a concept meant to account for the frequent discrepancy
      between an individual's measured level of brain pathology and her expected
      cognitive performance. It is particularly important within the context of aging
      and dementia, but has wider applicability to all forms of brain damage. As such,
      it has intimate links to related compensatory and neuroprotective concepts, as
      well as to the related notion of brain reserve. In this article, we introduce the
      concept of cognitive reserve and explicate its potential cognitive and neural
      implementation. We conclude that cognitive reserve is compatible and
      complementary with many related concepts, but that each much draw sharper
      conceptual boundaries in order to truly explain preserved cognitive function in
      the face of aging or brain damage. 

PMID- 24018147
TI  - Does menstrual bleeding decrease after ablation of intramural myomas? A
      retrospective study.
AB  - STUDY OBJECTIVE: To evaluate the effect of radiofrequency volumetric thermal
      ablation (RFVTA) on menstrual bleeding in patients with intramural myomas.
      DESIGN: Retrospective analysis of a recently completed prospective trial of
      laparoscopic ultrasound-guided RFVTA in which 135 subjects had objectively
      measured heavy menstrual bleeding (>=160 to <=500 mL) and confirmed submucosal,
      intramural, and subserosal myomas. We analyzed the pretreatment monthly menstrual
      blood loss as well as the response to treatment based on the types of myomas,
      specifically those subjects with only intramural myomas versus those with only
      submucosal myomas or those with both (Canadian Task Force classification II-2).
      SETTING: Outpatient hospital and private surgery centers. PATIENTS: One hundred
      thirty-five premenopausal symptomatic women (mean age: 42.4 +/- 4.5 years) with
      uterine myomas and heavy menstrual bleeding confirmed by alkaline hematin
      analysis. INTERVENTIONS: Laparoscopic ultrasound-guided RFVTA. MEASUREMENTS AND
      MAIN RESULTS: Menstrual blood loss (MBL) at baseline and at 12 months after the
      procedure was quantified in 122 subjects with intramural myomas (including those
      that abut the endometrium, those that are within the myometrium, and those that
      extend from the serosa into the myometrium) and/or submucous myomas. Although
      91.8% (112/122) of these subjects had 1 or more intramural myomas, submucous
      myomas were present in fewer than half of the subjects ([48.4%]). We identified
      10 subjects who had submucous but no intramural myomas. This group had a
      significant (-45.1%) posttreatment decrease in monthly bleeding (95% confidence
      interval [CI], -78.0% to -12.2%; p = .013). In this same study, there were 63
      subjects with intramural myomas and no submucosal myomas, and their posttreatment
      decrease in MBL of -31.8% was also clinically and statistically significant (95%
      CI, -41.4% to -22.2%; p<.001). Of those 63 subjects was a subset with intramural
      myomas (n = 27) without myomas abutting the endometrium or submucous myomas; this
      third set also resulted in a clinically and statistically significant reduction
      in MBL (-25.0% and -65.22 mL; 95% CI, -38.8% to -11.2%; p = .001). CONCLUSION:
      Although it has been known that the treatment of submucous myomas results in a
      reduction of MBL, this is the first study to show that radiofrequency ablative
      therapy for intramural myomas without a submucosal component will also result in
      a significant reduction in menstrual blood loss.

PMID- 24018148
TI  - When I was hungry and thirsty were you there?

PMID- 24018149
TI  - Outcome assessment in acute pancreatitis patients.
AB  - Early diagnosis and severity evaluation in patients with acute pancreatitis (AP)
      are very important due to its potential morbidity and mortality. Several
      clinical, laboratory, and radiologic factors, and many scoring systems have been
      proposed for outcome prediction. Although the Ranson and Acute Physiology and
      Chronic Health Evaluation II scoring systems have been widely used for decades,
      the cumbersome components partly limit their predictability. Recently, the
      Bedside Index for Severity in AP scoring system and series blood urea nitrogen
      changes, which are simple and convenient to evaluate within 24 hours after
      admission, have been validated for accuracy by several large-cohort studies. The
      presence of organ failure and systemic inflammatory response syndrome are also
      helpful to evaluate the severity of AP. Herein we review recent advances of the
      predictive methods for AP to provide an up-to-date perspective on outcome
      assessment of AP. 

PMID- 24018150
TI  - Reduction of RNA A-to-I editing in Drosophila acclimated to heat shock.
AB  - Although an increasing number of RNA adenosine-to-inosine (A-to-I) editing sites
      are being discovered, how the editing frequencies of these sites are modulated to
      fine-tune protein function in adaptive responses is not well understood. A
      previous study screening for heat tolerance in Drosophila mutants discovered a
      hypnos-2 mutant strain that was later found to be defective in dADAR, the
      Drosophila gene encoding the A-to-I editing enzyme. This supports the hypothesis
      that cells and organisms respond to stressful environments by ADAR (adenosine
      deaminase acting on RNA)-mediated RNA editing. Here, we investigated changes in
      the RNA A-to-I editing frequencies of 30 Drosophila nervous system targets in
      response to heat shock, a stress acclimatization that requires the dADAR
      function. To our surprise, most of these nervous system editing targets showed
      reduced editing. Our results suggest that a change in RNA editing pattern is a
      mechanism by which organisms acclimate to drastic environmental change. However,
      how RNA editing confers heat resistance is more complicated and requires further
      investigation. 

PMID- 24018151
TI  - A comparison between succinylcholine and rocuronium on the recovery profile of
      the laryngeal muscles during intraoperative neuromonitoring of the recurrent
      laryngeal nerve: a prospective porcine model.
AB  - The use of succinylcholine and rocuronium are reportedly feasible during
      intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) in
      thyroid surgery. This study aimed to investigate and compare the recovery
      profiles of succinylcholine and rocuronium on the laryngeal muscle during IONM of
      the RLN in a porcine model. Nine male Duroc-Landrace piglets were anesthetized
      with thiamylal and underwent tracheal intubation without neuromuscular blocking
      agents (NMBAs). Needle electrodes were inserted into the vocalis muscles through
      the cricothyroid ligament. The RLN was exposed and stimulated. Electromyographic
      (EMG) signals were obtained before and after the intravenous administration of a
      NMBA. The EMG amplitudes were measured before and after (at 1-minute intervals)
      the administration of the study drug until complete recovery. The study NMBA
      regimen included succinylcholine (1 mg/kg), low-dose rocuronium (0.3 mg/kg), and
      standard dose rocuronium (0.6 mg/kg). The maximal neuromuscular blockade and 80%
      recovery (i.e., duration) of the control responses were recorded and analyzed.
      The 80% recovery of the control response for succinylcholine (1 mg/kg) was 19.7
      +/- 1.5 minutes; low-dose rocuronium (0.3 mg/kg), 16.3 +/- 2.5 minutes; and
      standard dose rocuronium (0.6 mg/kg), 29.3 +/- 5.7 minutes. Succinylcholine (1
      mg/kg) and low-dose rocuronium (0.3 mg/kg) had significantly shorter durations
      than standard dose rocuronium (0.6 mg/kg). The EMG signal recovery returned to
      baseline within 30 minutes in the succinylcholine and low-dose rocuronium groups,
      but it did not return to baseline until 1 hour after surgery in the rocuronium
      (0.6 mg/kg) group. In this study, succinylcholine (1 mg/kg) and low-dose
      rocuronium (0.3 mg/kg) had favorable recovery profiles on the laryngeal muscle.
      It is recommended that low-dose rocuronium may replace succinylcholine for the
      induction of general anesthesia during IONM of the RLN in thyroid surgery.

PMID- 24018152
TI  - Effects of commercial citrate-containing juices on urolithiasis in a Drosophila
      model.
AB  - Diet modification plays an important role in nephrolithiasis. Development of an
      easy, ready-to-use beverage such as a commercial juice drink to use as a
      preventive treatment for renal calculi formation would be widely welcomed. We
      previously developed a novel Drosophila model for the study of nephrolithiasis.
      It provides a new well-established drug discovery platform for this common
      disease. In our current study, we used the Drosophila model to investigate the
      preventive effects of various commercial juices as potential treatments for
      nephrolithiasis. Our results showed that apple, cranberry, orange, and
      pomegranate juices failed to reduce calcium oxalate (CaOx) crystal formation,
      whereas our positive control-potassium citrate (K-citrate)-significantly
      prevented CaOx crystal formation. Unlike the commercial fruit juices that were
      tested, the administration of K-citrate significantly ameliorated the ethylene
      glycol (EG)-induced life-span reduction in treated flies. These results indicate
      that EG-induced CaOx nephrolithiasis in Drosophila can be prevented by K-citrate,
      but not by commercial citrate-containing juices. However, the inhibitory
      capability of citrate-containing juices to reduce renal stone formation in humans
      requires further elucidation.

PMID- 24018153
TI  - Is serum cystatin C an early predictor for acute kidney injury following
      cardiopulmonary bypass surgery in infants and young children?
AB  - Acute kidney injury (AKI) is a potential complication following cardiopulmonary
      bypass (CPB) surgery in infants and young children with congenital heart disease
      (CHD). The current pilot study evaluates the predictive value of serum cystatin C
      (CysC) for AKI after pediatric CPB surgery. We prospectively enrolled 43 children
      with CHD (30 males and 13 females) who underwent CPB surgery. They were aged 3
      years or younger. Serum CysC was measured at baseline and at 6 hours, 12 hours,
      24 hours, and 48 hours after initiating CBP. Twenty-one (48.8%) patients
      developed AKI after cardiac surgery. Children who developed AKI had more complex
      cardiac surgical procedures (based on the Risk Adjustment for Congenital Heart
      Surgery 1 [RACHS-1] category), a longer CPB duration, and a longer aortic
      clamping time (ACT). Serum concentrations of CysC postoperatively demonstrated an
      initial decline at 6 hours, a subsequent increase at 12 hours, and stabilized at
      24-48 hours. The best predictive performance was achieved 6 hours after CPB with
      an area under receiver operating characteristic curve (AUC) value of 0.69. The
      optimal cut-off value was 0.47 mg/L (sensitivity, 85.7%; specificity, 50%). By
      contrast, the RACHS-1 category, CPB duration, and ACT had higher AUC values at
      0.735, 0.791, and 0.731, respectively. In conclusion, serum CysC had limited
      predictive capacity and was not superior to clinical risk factors for the early
      detection of AKI after CPB surgery in this pilot study, which focused on infants
      and young children.

PMID- 24018154
TI  - Comparison of the efficacy and safety of selective laser trabeculoplasty in cases
      with primary open-angle glaucoma and pseudoexfoliative glaucoma.
AB  - The purpose of this study was to compare the efficacy and safety of selective
      laser trabeculoplasty (SLT) for patients with primary open-angle glaucoma (POAG)
      and pseudoexfoliative glaucoma (PXG). In this retrospective case series, 85 eyes
      (48 POAG, 37 PXG) of 85 patients were investigated. The medical records of
      patients who underwent SLT for POAG or PXG were reviewed. The main outcome
      measures included intraocular pressure (IOP)-lowering effect and ocular side
      effects. The mean decrease in IOP differed significantly (p < 0.001) between eyes
      with POAG (-4.4 +/- 2.1 mmHg) and eyes with PXG (-6.1 +/- 3.6 mmHg) at a mean
      follow-up period of 1 year. The rate of side effects, such as early IOP spike and
      uveitis, did not significantly differ between the two groups. In conclusion, SLT
      has a greater IOP-lowering effect in PXG compared with POAG.

PMID- 24018155
TI  - The impact of an interprofessional problem-based learning curriculum of clinical
      ethics on medical and nursing students' attitudes and ability of
      interprofessional collaboration: a pilot study.
AB  - Clinical ethic situations in modern multiprofessional healthcare systems may
      involve different healthcare professions who work together for patient care. The
      undergraduate interprofessional education of clinical ethics would help to
      incubate healthcare students' ability of interprofessional collaboration in
      solving ethical problems. However, the impact from an interprofessional
      educational model on student's attitudes and confidence of interprofessional
      collaboration should be carefully evaluated during the process of curricular
      development. This study aimed to conduct a pilot interprofessional PBL curriculum
      of clinical ethics and evaluate the curricular impact on interprofessional
      students' attitude and confidence of collaborative teamwork. Thirty-six medical
      and nursing students volunteered to participate in this study and were divided
      into three groups (medical group, nursing group, and mixed group). Tutors were
      recruited from the Medical School and the College of Nursing. The pilot
      curriculum included one lecture of clinical ethics, one PBL case study with two
      tutorial sessions, and one session of group discussion and feedback. A narrative
      story with multiple story lines and a multiperspective problem analysis tool were
      used in the PBL tutorials. The students' self-evaluation of learning
      questionnaire was used to evaluate students' learning of clinical ethics and
      interprofessional collaborative skills and attitude. The internal consistency of
      the questionnaire was measured by Cronbach alpha, and the criterion-related
      validity of the questionnaire was evaluated through associations between the
      dimension scores with the student group by one-way analysis of variance test
      (ANOVA) test and Tukey-Kramer honestly significant difference (HSD) comparison.
      There was significant difference among different groups in students' ability and
      attitudes about "interprofessional communication and collaboration" (p = 0.0184).
      The scores in the mixed group (37.58 +/- 3.26) were higher than the medical group
      (32.10 +/- 4.98). In conclusion, our model for the interprofessional PBL
      curriculum of clinical ethics is practicable and will produce positive impacts on
      students' attitudes and confidence of interprofessional collaboration.

PMID- 24018156
TI  - Primary pulmonary hepatoid carcinoma: report of a case and review of the
      literature.
AB  - Hepatoid carcinoma is a rare malignancy defined as extrahepatic primary alpha
      fetoprotein-producing carcinoma morphologically resembling hepatocellular
      carcinoma. It is extremely rare in the lungs, with ambiguous pathological
      descriptions and variable prognosis. Herein, we present the case of a 66-year-old
      man with a primary pulmonary hepatoid carcinoma in his right upper lung who
      received complete curative surgical resection and adjuvant chemotherapy. No signs
      of recurrence or distant metastasis have been observed for 57 months
      postoperation. In addition, the literature is reviewed and the pathological
      diagnostic pitfalls are discussed.

PMID- 24018157
TI  - Multiple myeloma with cavernous sinus involvement.

PMID- 24018158
TI  - Hypernatremia-associated coma caused by glucocorticoid replacement for adrenal
      crisis in an unrecognized central diabetes insipidus patient.

PMID- 24018159
TI  - Sexual activity after total hip arthroplasty: a motion capture study.
AB  - Relative risk of impingement and joint instability during sexual activities after
      total hip arthroplasty (THA) has never been objectively investigated. Hip range
      of motion necessary to perform sexual positions is unknown. A motion capture
      study with two volunteers was performed. 12 common sexual positions were captured
      and relevant hip joint kinematics calculated. The recorded data were applied to
      prosthetic hip 3D models to evaluate impingement and joint instability during
      motion. To explore the effect of acetabular component positioning, nine
      acetabular cup positions were tested. Four sexual positions for women requiring
      intensive flexion (> 95 degrees ) caused prosthetic impingements (associated with
      posterior instability) at 6 cup positions. Bony impingements (associated with
      anterior instability) occurred during one sexual position for men requiring high
      degree of external rotation (> 40 degrees ) combined with extension and adduction
      at all cup positions. This study hence indicates that some sexual positions could
      be potentially at risk after THA, particularly for women. 

PMID- 24018160
TI  - Custom cementless THA in patients with Legg-Calve-Perthes Disease.
AB  - Legg-Calve-Perthes disease is characterized by osteonecrosis of the femoral head
      during childhood. Outcomes of total hip arthroplasty (THA) for these patients are
      less satisfactory than for those with primary osteoarthritis, often complicated
      by young patient age, multi-planar deformities and previous childhood surgery. To
      our knowledge no one has reported the long-term outcomes of cementless custom
      made THA in patients with Legg-Calve-Perthes disease. We reviewed 15 THAs with an
      average follow-up of ten years. Survivorship rates of the femoral and acetabular
      components were 100% and 79% respectively. Mean Harris Hip Scores improved from
      41 preoperatively to 80 at final follow-up. With excellent functional outcome,
      custom-made cementless prostheses should be considered as a treatment option for
      osteoarthritis secondary to Legg-Calve-Perthes disease in the presence of
      abnormal proximal femoral and acetabular anatomy. 

PMID- 24018161
TI  - The impact of pre-operative weight loss on incidence of surgical site infection
      and readmission rates after total joint arthroplasty.
AB  - This study characterized a cohort of obese total hip arthroplasty (THA) and total
      knee arthroplasty (TKA) patients (1/1/2008-12/31/2010) and evaluated whether a
      clinically significant amount of pre-operative weight loss (5% decrease in body
      weight) is associated with a decreased risk of surgical site infections (SSI) and
      readmissions post-surgery. 10,718 TKAs and 4066 THAs were identified. During the
      one year pre-TKA 7.6% of patients gained weight, 12.4% lost weight, and 79.9%
      remained the same. In the one year pre-THA, 6.3% of patients gained weight, 18.0%
      lost weight, and 75.7% remained the same. In TKAs and THAs, after adjusting for
      covariates, the risk of SSI and readmission was not significantly different in
      the patients who gained or lost weight pre-operatively compared to those who
      remained the same. 

PMID- 24018162
TI  - Nanog, a novel prognostic marker for lung cancer.
AB  - OBJECTIVE: To investigate the expression of the stem cell marker Nanog in lung
      cancer tissues and the correlations between Nanog expression and clinic
      pathologic characteristics as well as prognosis of lung cancer. METHODS: 163
      patients with lung cancers enrolled in the study. The expression of Nanog in the
      cell lines and lung cancers were evaluated by RT-PCR, immunofluorescence and
      immunohistochemisty. Then, the correlations between Nanog expression status and
      clinic-pathologic characteristics and prognosis of lung cancer patients were
      analyzed. RESULTS: It showed that Nanog are higher expressed in lung cancer
      tissues compared to their normal counterparts in both mRNA and protein levels,
      and Nanog expression was observed to be positively correlated with tumor
      differentiation and clinical stages of lung cancer patients (P = 0.001 and
      0.001). Nanog were mainly localized at the cytoplasm in the brown color in the
      lung cancers. In addition, nuclear staining of Nanog was more observed in poorly
      differentiated lung cancers compared to others (P = 0.01). Furthermore, survival
      analyses showed that over-expression of Nanog protein predicted a worse prognosis
      for lung cancer patients (P = 0.001). CONCLUSION: Nanog can be an important
      prognostic marker for lung cancer, which may present a new therapeutic target for
      lung cancer patients in the future.

PMID- 24018163
TI  - Assessing the precision of strain measurements using electron backscatter
      diffraction--part 1: detector assessment.
AB  - We analyse the link between precision of pattern shift measurements and the
      resolution of the measurement of elastic strain and lattice rotation using high
      resolution electron backscatter diffraction (HR-EBSD). This study combines
      analysis of high quality experimentally obtained diffraction patterns from single
      crystal silicon; high quality dynamical simulations using Bloch wave theory;
      quantitative measurements of the detector Modulation Transfer Function (MTF) and
      a numerical model. We have found that increases in exposure time, when 1*1
      binning is selected, are the primary reason for the observed increase in
      sensitivity at greater than 2*2 binning and therefore use of software integration
      and high bit depth images enables a significant increase in strain resolution.
      This has been confirmed using simulated diffraction patterns which provide
      evidence that the ultimate theoretical resolution of the cross correlation based
      EBSD strain measurement technique with a 1000*1000 pixel image could be as low as
      4.2*10(-7) in strain based on a shift precision of 0.001 pixels. 

PMID- 24018164
TI  - The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell
      malignancies: insight into disease biology and new targeted therapies.
AB  - Over the last decade, the active role of the microenvironment in the pathogenesis
      of B cell lymphomas has been recognized, delivering signals that favor clonal
      expansion and drug resistance. We are only beginning to understand the complex
      cross talk between neoplastic B cells and the tissue microenvironment, for
      example in secondary lymphoid organs, but some key cellular and molecular players
      have emerged. Mesenchymal stromal cells, nurselike cells (NLC) and lymphoma
      associated macrophages (LAM), in concert with T cells, natural killer cells and
      extracellular matrix components participate in the dialog with the neoplastic B
      cells. B cell receptor signaling, activation via TNF family members (i.e. BAFF,
      APRIL), and tissue homing chemokine receptors and adhesion molecules are
      important in the interaction between malignant B cells and their
      microenvironment. Disrupting this cross talk is an attractive novel strategy for
      treating patients with B cell malignancies. Here, we summarize the cellular and
      molecular interactions between B cell lymphoma/leukemia cells and their
      microenvironment, and the therapeutic targets that are emerging, focusing on
      small molecule inhibitors that are targeting B cell receptor-associated kinases
      SYK, BTK, and PI3Ks, as well as on immunomodulatory agents and T cell mediated
      therapies. Clinically relevant aspects of new targeted therapeutics will be
      discussed, along with an outlook into future therapeutic strategies. 

PMID- 24018165
TI  - Epigenetic regulation of hepatocellular carcinoma in non-alcoholic fatty liver
      disease.
AB  - Emerging evidence that epigenetics converts alterations in nutrient and
      metabolism into heritable pattern of gene expression has profound implications in
      understanding human physiology and diseases. Non-alcoholic fatty liver disease
      (NAFLD) is the hepatic manifestation of metabolic syndrome including obesity and
      diabetes which elevate the risk of hepatocellular carcinoma (HCC) especially in
      male. This review focuses on the molecular connections between metabolic
      dysfunction and aberrant epigenetic alterations in the development of HCC in
      NAFLD. The metabolites derived from excessive insulin, glucose and lipid may
      perturb epigenetic gene regulation through DNA methylation, histone
      modifications, and RNA interference, leading to activation of pro-inflammatory
      signaling and deregulation of metabolic pathways. The interplay and crosstalk of
      chromatin-modifying enzymes, microRNAs, signaling pathways and the downstream
      transcription factors result in epigenomic reprogramming that drives
      hepatocellular transformation. The interactions between sex hormone pathways and
      the epigenetic machineries that influence chromatin states in NAFLD provide
      potential molecular mechanisms of gender disparity in HCC. A deeper understanding
      of these connections and comprehensive molecular catalog of hepatocarcinogenesis
      may shed light in the identification of druggable epigenetic targets for the
      prevention and treatment of HCC in obese or diabetic patients. 

PMID- 24018166
TI  - Fourteen-year trends in sodium content of menu offerings at eight leading fast
      food restaurants in the USA.
AB  - OBJECTIVE: To examine changes in the Na content of lunch/dinner menu offerings at
      eight of the leading fast-food restaurants in the USA between 1997/1998 and
      2009/2010. DESIGN: Menu offerings and nutrient composition information for the
      menu items were obtained from archival versions of the University of Minnesota
      Nutrition Coordinating Center (NCC) Food and Nutrient Database. Nutrient
      composition information for lunch/dinner menu items sold by the fast-food
      restaurants included in the present study was updated in the database biannually.
      Menus were analysed for changes in mean Na content of all menu offerings (except
      beverages) and specific categories of menu items among all restaurants and for
      each individual restaurant. SETTING USA SUBJECTS: Lunch/dinner food menu of eight
      leading US fast-food restaurants. RESULTS: Between 1997/1998 and 2009/2010 the
      mean Na content of menu offerings across the eight restaurants increased by 23.4
      %. Examining specific food categories, mean Na content of entrees by increased
      17.2 % and that of condiments increased by 26.1 %. Only side dishes showed a
      decrease of 6.6 %. None of the restaurants examined had a decrease in Na across
      the lunch/dinner menu offerings over the 14 years examined. CONCLUSIONS: Results
      suggest that over the time period studied there has been no meaningful reduction
      in the Na content of lunch/dinner menu offerings at the leading fast-food
      restaurants examined in the present study.

PMID- 24018167
TI  - Editorial overview.

PMID- 24018168
TI  - Molecular and histological identification of Marteilioides infection in Suminoe
      Oyster Crassostrea ariakensis, Manila Clam Ruditapes philippinarum and Pacific
      Oyster Crassostrea gigas on the south coast of Korea.
AB  - The oyster ovarian parasite Marteilioides chungmuensis has been reported from
      Korea and Japan, damaging the oyster industries. Recently, Marteilioides-like
      organisms have been identified in other commercially important marine bivalves.
      In this study, we surveyed Marteilioides infection in the Manila clam Ruditapes
      philippinarum, Suminoe oyster Crassostrea ariakensis, and Pacific oyster
      Crassostrea gigas, using histology and Marteilioides-specific small subunit (SSU)
      rDNA PCR. The SSU rDNA sequence of M. chungmuensis (1716 bp) isolated from C.
      gigas in Tongyoung bay was 99.9% similar to that of M. chungmuensis reported in
      Japan. Inclusions of multi-nucleated bodies in the oocytes, typical of
      Marteilioides infection, were identified for the first time in Suminoe oysters.
      The SSU rDNA sequence of a Marteilioides-like organism isolated from Suminoe
      oysters was 99.9% similar to that of M. chungmuensis. Marteilioides sp. was also
      observed from 7 Manila clams of 1840 individuals examined, and the DNA sequences
      of which were 98.2% similar to the known sequence of M. chungmuensis. Unlike
      Marteilioides infection of Pacific oysters, no remarkable pathological symptoms,
      such as large multiple lumps on the mantle, were observed in infected Suminoe
      oysters or Manila clams. Distribution of the infected Manila clams, Suminoe
      oysters and Pacific oysters was limited to small bays on the south coast,
      suggesting that the southern coast is the enzootic area of Marteilioides
      infection.

PMID- 24018169
TI  - Efficacy of entomopathogenic bacteria for control of Musca domestica.
AB  - The aim of this study was to evaluate the larvicidal activity, and sub lethal
      effects of entomopathogenic bacteria Brevibacillus laterosporus, Bacillus
      thuringiensis var. israelensis, B. thuringiensis var. kurstaki, and a commercial
      formulation of Bacillus sphaericus on Musca domestica. Bacterial suspensions were
      prepared in different concentrations and added to the diet of newly-hatched
      larvae which were monitored until the adult stage. The larvae were susceptible to
      the B. laterosporus, B. thuringiensis var. israelensis, and B. thuringiensis var.
      kurstaki bacteria in varied concentration levels. These bacteria have larvicidal
      and sub lethal effects on the development of flies, reducing both adult size, and
      impairing the reproductive performance of the species. 

PMID- 24018170
TI  - Experimental infections of Orchitophrya stellarum (Scuticociliata) in American
      blue crabs (Callinectes sapidus) and fiddler crabs (Uca minax).
AB  - Outbreaks of an unidentified ciliate have occurred on several occasions in blue
      crabs from Chesapeake Bay held during winter months in flow-through systems. The
      parasite was initially thought to be Mesanophrys chesapeakensis, but molecular
      analysis identified it as Orchitophyra stellarum, a facultative parasite of sea
      stars (Asteroidea). We investigated the host-parasite association of O. stellarum
      in the blue crab host. Crabs were inoculated with the ciliate, or they were held
      in bath exposures after experimentally induced autotomy of limbs in order to
      determine potential mechanisms for infection. Crabs inoculated with the ciliate,
      or exposed to it after experimental autotomy, rapidly developed fatal infections.
      Crabs that were not experimentally injured, but were exposed to the ciliate,
      rarely developed infections; thus, indicating that the parasite requires a wound
      or break in the cuticle as a portal of entry. For comparative purposes, fiddler
      crabs, Uca minax, were inoculated with the ciliate in a dose-titration
      experiment. Low doses of the ciliate (10 per crab) were sometimes able to
      establish infections, but high intensity infections developed quickly at doses
      over 500 ciliates per crab. Chemotaxis studies were initiated to determine if the
      ciliate preferentially selected blue crab serum (BCS) over other nutrient
      sources. Cultures grown on medium with BCS or fetal bovine serum showed some
      conditioning in their selection for different media, but the outcome in choice
      experiments indicated that the ciliate was attracted to BCS and not seawater. Our
      findings indicate that O. stellarum is a facultative parasite of blue crabs. It
      can cause infections in exposed crabs at 10-15 degrees C, but it requires a
      portal of entry for successful host invasion, and it may find injured hosts using
      chemotaxis. 

PMID- 24018171
TI  - Normal social evaluations of faces in acquired prosopagnosia.

PMID- 24018172
TI  - Intranasal fungal (Alternaria) infection related to nasal steroid spray.
AB  - During the past three decades intranasal corticosteroid sprays have been proven
      to be efficient and reasonably safe for the treatment of rhinitis, sinusitis and
      nasal polyposis. The adverse effects are generally localized and self-limited and
      rarely systemic or significant. We report an immunocompetent female treated with
      triamcinolone acetonide nasal spray for chronic rhinitis in whom an intranasal
      fungal infection with Alternaria species developed three months later. The
      infection was refractory to topical therapies alone, and was resolved with a
      combination of systemic and topical antifungal therapy. We also described the
      clinical manifestations of this rare infection and our therapeutic experience. In
      addition, we reviewed previous literature of fungal infections related to nasal
      corticosteroid sprays and compared them with our report. 

PMID- 24018173
TI  - Vibrational spectroscopic study of the uranyl selenite mineral derriksite
      Cu4UO2(SeO3)2(OH)6.H2O.
AB  - Raman spectrum of the mineral derriksite Cu4UO2(SeO3)2(OH)6?H2O was studied and
      complemented by the infrared spectrum of this mineral. Both spectra were
      interpreted and partly compared with the spectra of demesmaekerite, marthozite,
      larisaite, haynesite and piretite. Observed Raman and infrared bands were
      attributed to the (UO2)(2+), (SeO3)(2-), (OH)(-) and H2O vibrations. The presence
      of symmetrically distinct hydrogen bonded molecule of water of crystallization
      and hydrogen bonded symmetrically distinct hydroxyl ions was inferred from the
      spectra in the derriksite unit cell. Approximate U-O bond lengths in uranyl and O
      H...O hydrogen bond lengths were calculated from the Raman and infrared spectra
      of derriksite.

PMID- 24018174
TI  - Growth and survival of Halimione portulacoides stem cuttings in heavy metal
      contaminated soils.
AB  - The halophytic shrub Halimione portulacoides demonstrates a high tolerance to
      heavy metal contamination and a capacity for accumulating metals within its
      tissues. On the Iberian Peninsula, this species has colonized habitats with high
      levels of metal pollution. The aim of this study is to analyze the response of H.
      portulacoides stem cuttings to this pollution. Growth, photosynthesis and metal
      uptake were examined in H. portulacoides through an experiment in which stem
      cuttings were replanted in metal-contaminated soil. This condition decreased
      growth and lowered both photosynthetic rate and stomatal conductance. Reduced
      photosynthetic performance was largely due to the reduced concentration of
      photosynthetic pigments. Despite these responses, there was some important
      evidence suggesting the phytoremediatory potential of Halimione stem cuttings.
      The results of our study indicate that this salt-marsh shrub may represent a
      biotool of value in the restoration of polluted areas.

PMID- 24018175
TI  - E-cigarettes as good as patches in helping to reduce smoking, study concludes.

PMID- 24018176
TI  - Cystic fibrosis and pregnancy in the modern era: a case control study.
AB  - BACKGROUND: Increasingly, women with cystic fibrosis become pregnant. Outcomes of
      these women need further study particularly in the setting of improved survival
      in CF. METHODS: We performed a case-control study of pregnant CF women including
      22 matched pairs with an average follow-up of 4.5 years. Nutritional outcomes,
      changes in lung function, and exacerbation rates were compared. RESULTS: Matched
      pairs were similar in age, sweat chloride, FEV1 and FVC % predicted, BMI, and
      diabetes status. Change in BMI, FEV1 and FVC % predicted at the end of pregnancy
      and at last follow-up were similar between groups. Moreover, rates of
      exacerbation before, during and after pregnancy were similar. On multivariable
      analysis pregnancy had no effect on change in lung function over the study
      period. Significant predictors of decline included higher pre-pregnancy lung
      function and pancreatic insufficiency. CONCLUSIONS: Pregnancy does not lead to
      immediate or medium-term adverse effects for CF patients.

PMID- 24018178
TI  - A novel method of post-pyloric feeding tube placement at bedside.
AB  - PURPOSE: Post-pyloric feeding tube placement is often difficult, and special
      equipment or peristalsis agents are used to aid insertion. Although several
      reports have described blind techniques for post-pyloric feeding-tube placement,
      no general consensus about method preference has been achieved. MATERIALS AND
      METHODS: The technique is performed as follows: via the nostril, a stylet-tipped
      feeding tube is advanced about 70 cm; to confirm tip location to the right of the
      epigastric area, towards the right hypochondriac region, 5 mL shots of air are
      injected to enable touch detection of bubbling; finally, the tube is advanced to
      a length of 100 cm, during which the strength of bubbling seems to diminish under
      palpation. RESULTS: We prospectively enrolled consecutive patients whose oral
      intake was expected to be difficult for 48 hours in the intensive care unit.
      Forty-one patients were enrolled and the rate of successful placement at first
      attempt was 95.1%. Mean duration for successful placement was 15 minutes.
      CONCLUSIONS: With a novel technique, from the bedside, without special tools or
      drugs, we successfully placed post-pyloric feeding tubes. Essential points when
      inserting the tube are confirmation of the location of the tube tip by palpation
      of injected air, and to avoid deflection and looping.

PMID- 24018179
TI  - Novel hemotropic Mycoplasma species in white-tailed deer (Odocoileus
      virginianus).
AB  - Globally, hemotropic Mycoplasma spp. are emerging or re-emerging zoonotic
      pathogens that affect livestock, wildlife, companion animals, and humans,
      potentially causing serious and economically important disease problems. Little
      is known about hemotropic Mycoplasma spp. prevalence, host-specificity, or route
      of transmission in most species, including wildlife. DNA amplification by PCR
      targeting the 16SrRNA and the RNaseP genes was used to establish the presence and
      prevalence of hemotropic Mycoplasma spp. in a white-tailed deer (O. virginianus)
      population in eastern North Carolina. Sixty-five deer (89%) tested positive for
      hemotropic Mycoplasma spp. where sequence analysis of the 16SsRNA and the RNaseP
      genes indicated the presence of at least three distinct species. This study
      represents the first detection of three distinct hemotropic Mycoplasma species in
      white-tailed deer and the first report of two novel hemotropic Mycoplasma
      species. 

PMID- 24018177
TI  - Impact of azithromycin treatment on macrophage gene expression in subjects with
      cystic fibrosis.
AB  - BACKGROUND: Azithromycin treatment improves clinical parameters in patients with
      CF, and alters macrophage activation from a pro-inflammatory (M1) phenotype to a
      pro-fibrotic, alternatively activated (M2) phenotype. The transcriptional profile
      of cells from patients receiving azithromycin is unknown. METHODS: Gene
      expression in association with macrophage polarization, inflammation, and tissue
      remodeling was assessed from sputum samples collected from patients with CF.
      Transcriptional profiles and clinical characteristics, including azithromycin
      therapy, were compared. RESULTS: Expression of NOS2 and TNFalpha was decreased in
      subjects receiving azithromycin, whereas expression of M2-associated genes was
      unaffected. Principal component analysis revealed gene expression profiles
      consistent with M1- (MMP9, NOS2, and TLR4) or M2-polarization (CCL18,
      fibronectin, and MR1) in select subject groups. These expression signatures did
      not significantly correlate with clinical characteristics. CONCLUSIONS: Pro
      inflammatory gene expression was low in subjects receiving AZM. Genes were
      stratified into groupings characteristic of M1- or M2-polarization, suggesting
      that overall polarization status is distinct among patient groups.

PMID- 24018180
TI  - Study of ehrlichiosis in kennel dogs under treatment and prevention during seven
      months in Dakar (Senegal).
AB  - In Dakar kennels where morbidity and mortality attributed to diseases transmitted
      by ticks were high, we conducted a field study to assess the prevalence of
      Ehrlichia canis, Anaplasma platys and Babesia spp. infections in two kennels (n =
      34 dogs) and to study the impact of tick protection. The first day of the study,
      the E. canis PCR were positive in 18 dogs (53%). A. platys was found in one dog
      and all dogs were negative for Babesia spp. After one month of doxycycline
      treatment, the number of PCR positive dogs decreased significantly to 2 (5.9%).
      During seven months, all dogs were treated monthly topically with a novel
      combination (Certifect((r)), Merial) delivering at least 6.7 mg fipronil/kg body
      weight, 8.0mg amitraz/kg and 6 mg (S)-methoprene/kg. The number of PCR positive
      dogs remained stable all over the seven months, with 4 dogs being positive at Day
      90 and 2 at Day 210. The combination of treatment and monthly prevention had a
      significant effect in the two kennels. All dogs remained healthy, which was not
      the case in previous years.

PMID- 24018181
TI  - Parasites of the grouper fish Epinephelus coioides (Serranidae) as potential
      environmental indicators in Indonesian coastal ecosystems.
AB  - A total of 195 Epinephelus coioides (Hamilton, 1822) were studied for fish
      parasites from Javanese (Segara Anakan lagoon) and Balinese waters. Up to 25
      different parasite species belonging to the following taxa: one Ciliata, one
      Microsporea, five Digenea, one Monogenea, four Cestoda, four Nematoda, one
      Acanthocephala, one Hirudinea and seven Crustacea were identified with four new
      host and locality records. The dominant parasites included the monogenean
      Pseudorhabdosynochus lantauensis (53.3-97.1%), the nematode Spirophilometra
      endangae (23.3-42.9%), the digenean Didymodiclinus sp. (2.9-40.0%), the nematodes
      Philometra sp. (22.6-34.3%) and Raphidascaris sp. (2.9-28.6%), and the isopod
      Alcirona sp. (6.7-31.4%). Regional differences for E. coioides were found in
      terms of endoparasite diversity, total diversity according to Shannon-Wiener,
      Simpson index and Evenness. A comparison with published data from Sumatera
      revealed highest endoparasite diversity (Shannon-Wiener: 1.86/1.67-2.04) and
      lowest ectoparasite/endoparasite ratio (0.73/0.57-0.88) off the Balinese coast,
      followed by Lampung Bay, Sumatera (1.84; 0.67), off the coast of Segara Anakan
      lagoon (1.71; 0.71), and in the lagoon (0.30/0.19-0.66; 0.85/0.67-1.00). The
      presented data demonstrate the natural range of these parameters and parasite
      prevalences according to habitat and region, allowing adjustment of the scale
      that has been used in the visual integration of the parasite parameters into a
      star graph. The parasite fauna of E. coioides in Segara Anakan lagoon 'improved'
      from 2004 until 2008/09, possibly related to earlier oil spill events in 2002 and
      2004. The use of grouper fish parasites as an early warning system for
      environmental change in Indonesian coastal ecosystems is discussed. 

PMID- 24018183
TI  - Three-dimensional morphological and mineralogical characterization of testate
      amebae.
AB  - Testate amebae are unicellular shelled protozoa commonly used as indicators in
      ecological and paleoecological studies. We explored the potential application of
      three-dimensional (3D) X-ray micro-tomography used in addition to 2D techniques
      (environmental scanning electron microscopy, electron probe micro-analysis, and
      cathodoluminescence) for detailed characterization of agglutinated shells of
      protozoa. We analyzed four specimens of the aquatic testate ameba Difflugia
      oblonga (Arcellinida), to test whether size distribution and mineral composition
      of shell grains diverged from sediment size distribution and mineralogical
      composition. From the 3D images, the geometry of the specimens (size and mass)
      and of the individual grains forming the specimen (grain size distribution and
      volume) were calculated. Based on combined chemical, mineralogical, and
      morphological analyses we show that D. oblonga is able to selectively pick up the
      small size fraction of the sediment with a preference for low-density silicates
      close to quartz density (~2.65). The maximum size of the grains matches the size
      of the pseudostome (shell aperture), suggesting the existence of a physical limit
      to grain size used for building the shell. This study illustrates the potential
      of this combined approach to characterize agglutinated shells of protozoa. This
      data can be useful for detailed morphological studies with applications in
      taxonomy and ecology. 

PMID- 24018182
TI  - Sex differences and steroid modulation of cardiac iron in a mouse model of iron
      overload.
AB  - Iron cardiomyopathy is the leading cause of death in transfusional iron overload,
      and men have twice the mortality of women. Because the prevalence of cardiac iron
      overload increases rapidly during the second decade of life, we postulated that
      there are steroid-dependent sex differences in cardiac iron uptake. To test this
      hypothesis, we manipulated sex steroids in mice with constitutive iron absorption
      (homozygous hemojuvelin knockout); this model mimics the myocyte iron deposition
      observed in humans. At 4 weeks of age, female mice were ovariectomized (OVX) and
      male mice were castrated (OrchX). Female mice received an estrogen implant (OVX +
      E) or a cholesterol control (OVX), whereas male mice received an implant
      containing testosterone (OrchX + T), dihydrotestosterone (OrchX + DHT), estrogen
      (OrchX + E), or cholesterol (OrchX). All animals received a high-iron diet for 8
      weeks. OrchX, OVX, and OVX + E mice all had similar cardiac iron loads. However,
      OrchX + E males had a significant increase in cardiac iron concentration compared
      with OrchX mice (P < 0.01), whereas the OrchX + T and OrchX + DHT groups only
      trended higher (P < 0.06 and P < 0.15, respectively). Hormone treatments did not
      impact liver iron concentration in either sex. When data were pooled across
      hormone therapies, liver iron concentration was 25% greater in males than females
      (P < 0.01). In summary, we found that estrogen increased cardiac iron loading in
      male mice, but not in females. Male mice loaded 25% more hepatic iron than female
      mice regardless of the hormone treatment.

PMID- 24018184
TI  - Risks for fishborne zoonotic trematodes in tilapia production systems in
      Guangdong province, China.
AB  - Guangdong province is the most important region for tilapia culture in China.
      However, it is also an endemic region for fishborne zoonotic trematodes (FZT),
      which pose a risk to human food safety and health. A study was designed to assess
      the status of trematode parasite infections in tilapia aquaculture systems as an
      indicator of potential risks from FZT associated with consumption of tilapia.
      Tilapia from nursery and grow-out ponds were sampled from monoculture,
      polyculture and integrated aquaculture systems. The results from 388 tilapia
      examined revealed a very low prevalence (1.5%) of trematode infections
      (Heterophyidae and Echinostomatidae). Integrated systems using animal manure and
      latrine wastes as fertilizer did not show a higher prevalence of FZT. Because it
      was not clear whether the low risk of infection was attributable to existing
      effective pond management practices or a low risk of spillover of FZT from area
      sylvatic reservoir hosts, a survey of local wild-caught fish was conducted. Five
      species of FZT were discovered from a total of 271 wild-caught fish and a mean
      infection density of 4.0 metacercariae/100g; FZT discovered included intestinal
      flukes (Haplorchis spp., Procerovum varium, and Metagonimus spp.) and
      metacercariae tentatively identified as Clonorchis sinenesis. The common
      occurrence of FZT in wild-caught fish suggests that the presence of FZT in local
      wild animal reservoirs is substantial, and that although the current aquaculture
      management systems for tilapia are generally effective in preventing transmission
      of these parasites into tilapia production systems, the improvement of pond
      management practices and biosecurity must be maintained at a high level. 

PMID- 24018185
TI  - Analysis using canine peripheral blood for establishing in vitro conditions for
      monocyte differentiation into macrophages for Leishmania chagasi infection and T
      cell subset purification.
AB  - Canine visceral leishmaniasis (CVL) is a parasitic disease endemic in many
      countries, and dogs present as the major natural reservoir of the parasite,
      Leishmania chagasi (syn. L. infantum). Biomarkers in the canine immune system is
      an important technique in the course of developing vaccines and treatment
      strategies against CVL. New methodologies for studying the immune response of
      dogs during Leishmania infection and after receiving vaccines and treatments
      against CVL would be useful. In this context, we used peripheral blood
      mononuclear cells (PBMCs) from healthy dogs to evaluate procedures related to (i)
      establishment of in vitro conditions of monocytes differentiated into macrophages
      infected with L. chagasi and (ii) purification procedures of T-cell subsets
      (CD4(+) and CD8(+)) using microbeads. Our data demonstrated that after 5 days of
      differentiation, macrophages were able to induce significant phagocytic and
      microbicidal activity after L. chagasi infection and also showed increased
      frequency of parasitism and a higher parasite load. Although N-acetyl-beta-d
      glucosaminidase (NAG) levels presented similar levels of macrophage culture and
      L. chagasi infection, a progressive decrease in myeloperoxidase (MPO) levels was
      a hallmark over 5 days of culture. High purity levels (>90%) of CD4 and CD8 T
      cells were obtained on a magnetic separation column. We concluded that monocytes
      differentiated into macrophages at 5 days and displayed an intermediate frequency
      of parasitism and parasite load 72 h after L. chagasi infection. Furthermore, the
      purification system using canine T-lymphocyte subsets obtained after 5 days of
      monocyte differentiation proved efficient for CD4 or CD8 T-cell purification
      (>=90%). The in vitro analysis using L. chagasi-infected macrophages and purified
      T cells presented a prospective methodology that could be incorporated in CVL
      vaccine and treatment studies that aim to analyze the microbicidal potential
      induced by specific CD4(+) and/or CD8(+) T cells.

PMID- 24018186
TI  - Incidence of head and neck cancer and socioeconomic status in Canada from 1992 to
      2007.
AB  - OBJECTIVE: To investigate the association between head and neck cancer (HNC)
      incidence and socioeconomic status (SES) in Canada, and investigate changes in
      the relationship between HNC incidence and SES from 1992 to 2007. MATERIALS AND
      METHODS: Cases were drawn from the Canadian Cancer Registry (1992-2007), and were
      categorized into three subsites: oropharynx, oral cavity, and "other"
      (hypopharynx, larynx, and nasopharynx). Demographic and socioeconomic information
      were extracted from the Canadian Census of Population data for the study period
      (1992-2007), which included four census years. We linked cases to income
      quintiles (InQs) according to patients' postal codes. RESULTS: Incidence rates in
      the lowest InQs were significantly higher than in the highest InQs for all HNC
      subsites. The incidence of oropharyngeal cancer increased over the time period
      1992-2007 for all InQs. However, the greatest increase in incidence was in the
      highest InQs. As a result, over the time period the gap between the incidence of
      the highest and lowest InQs significantly narrowed for oropharyngeal cancer. For
      oral cavity cancer and the other head and neck cancers, the overall incidence did
      not increase and the gap in incidence did not change significantly. CONCLUSION:
      HNC incidence was higher with lower income in all HNC subsites in Canada from
      1992 to 2007. The gap in incidence between the highest and the lowest InQs
      narrowed for oropharyngeal cancer over the time period studied, but was unchanged
      for the other HNC subsites.

PMID- 24018187
TI  - Discovery of oral and inhaled PDE4 inhibitors.
AB  - The optimization of oxazole-based PDE4 inhibitor 1 has led to the identification
      of both oral (compound 16) and inhaled (compound 34) PDE4 inhibitors. Selectivity
      against PDE10/PDE11, off target screening, and in vivo activity in the rat are
      discussed. 

PMID- 24018189
TI  - Natural-product-based insecticidal agents 14. Semisynthesis and insecticidal
      activity of new piperine-based hydrazone derivatives against Mythimna separata
      Walker in vivo.
AB  - In continuation of our program aimed at the discovery and development of natural
      product-based insecticidal agents, twenty-six new piperine-based hydrazone
      derivatives were synthesized from piperine, an alkaloid isolated from Piper
      nigrum Linn. The single-crystal structures of 6c, 6q and 6w were unambiguously
      confirmed by X-ray crystallography. Their insecticidal activity was evaluated
      against the pre-third-instar larvae of Mythimna separata Walker in vivo.
      Especially compounds 6b, 6i and 6r, the final mortality rates of which, at the
      concentration of 1 mg/mL, were 62.1%, 65.5% and 65.5%, respectively, exhibited
      more pronounced insecticidal activity compared to toosendanin at 1 mg/mL, a
      commercial botanical insecticide isolated from Melia azedarach. It suggested that
      introduction of the substituents at the C-2 position on the phenyl ring of the
      hydrazone derivatives was important for their insecticidal activity.

PMID- 24018188
TI  - Influences of hydrocarbon linkers on the receptor binding affinities of
      gonadotropin-releasing hormone peptides.
AB  - Three new DOTA-conjugated GnRH peptides with various hydrocarbon linkers were
      synthesized to evaluate the influences of the linkers on their receptor binding
      affinities. The hydrocarbon linker displayed a profound impact on the receptor
      binding affinities of DOTA-conjugated GnRH peptides. The Aun linker was better
      than Gaba, Ahx and Aoc linkers in retaining strong receptor binding affinity of
      the GnRH peptide. DOTA-Aun-(D-Lys(6)-GnRH) displayed 22.8 nM GnRH receptor
      binding affinity. (111)In-DOTA-Aun-(D-Lys(6)-GnRH) exhibited fast tumor uptake
      and urinary clearance in MDA-MB-231 human breast cancer-xenografted nude mice.
      The cellular and biological results provided an insight into the design of new
      GnRH peptides in the future.

PMID- 24018190
TI  - Setting expectations in molecular optimizations: Strengths and limitations of
      commonly used composite parameters.
AB  - Over the past 15years there have been extensive efforts to understand and reduce
      the high attrition rates of drug candidates with an increased focus on
      physicochemical properties. The fruits of this labor have been the generation of
      numerous efficiency indices, metric-based rules and visualization tools to help
      guide medicinal chemists in the design of new compounds with more favorable
      properties. This deluge of information may have had the unintended consequence of
      further obfuscating molecular optimizations by the inability of these scoring
      functions, rules and guides to reach a consensus on when a particular
      transformation is identified as beneficial. In this manuscript, several composite
      parameters, or efficiency indices, are examined utilizing theoretical and
      experimental matched molecular pair analyses in order to understand the basis for
      how each will perform under varying scenarios of molecular optimizations. In
      contrast to empirically derived composite parameters based on heavy atom count,
      lipophilic efficiency (LipE) sets consistent expectations regardless of molecular
      weight or relative potency and can be used to generate consistent expectations
      for any matched molecular pair. 

PMID- 24018191
TI  - Anti-proliferative activity of hydnocarpin, a natural lignan, is associated with
      the suppression of Wnt/beta-catenin signaling pathway in colon cancer cells.
AB  - Based on the Wnt inhibitors as potential targets in the development of anticancer
      agents, natural compounds were evaluated for beta-catenin-mediated
      transcriptional activity. A natural lignan hydnocarpin isolated from Lonicera
      japonica was considered a potential inhibitor for Wnt/beta-catenin signalings.
      The anti-proliferative activity of hydnocarpin was also found to be associated
      with the suppression of Wnt/beta-catenin-mediated signaling pathway in human
      colon cancer cells. These data suggest that hydnocarpin might be a novel Wnt
      inhibitor and has a potential of signaling regulator in beta-catenin-mediated
      signaling pathways. 

PMID- 24018192
TI  - Insight into dihalogenation of E-ring of podophyllotoxins, and their acyloxyation
      derivatives at the C4 position as insecticidal agents.
AB  - Unexpected sequential E-ring dihalogenation of podophyllotoxin analogues is
      reported. It demonstrated that a chlorine/bromine atom was prior introduced at
      the C2' position of podophyllotoxin, and the corresponding free rotation of E
      ring around the C1-C1' bond of 2'-chloro or 2'-bromopodophyllotoxin was
      restricted. When 2'-chloro or 2'-bromopodophyllotoxin reacted with N
      chlorosuccinimide (NCS), the chlorine atom was regioselectively introduced at
      their C6' position on the E-ring. Whereas 2'-chloro or 2'-bromopodophyllotoxin
      reacted with NBS, the bromine atom was regioselectively introduced at their C5
      position on the B-ring. When 2'-chloropodophyllotoxin reacted with different
      carboxylic acids in the presence of BF3.Et2O, the steric effect of its E-ring for
      stereoselective synthesis of 4beta-acyloxy-2'-chloropodophyllotoxin derivatives
      was observed. The insecticidal activity of 2'(2',6')-(di)halogen-substituted
      podophyllotoxin derivatives were evaluated with Mythimna separata Walker. 

PMID- 24018193
TI  - Synthesis and biological evaluation of biotin conjugates of (+/-)-(4bS,8aR,10aS)
      10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydro
      phenanthrene-2,6-dicarbonitrile, an activator of the Keap1/Nrf2/ARE pathway, for
      the isolation of its protein targets.
AB  - The tricycle 1 ((+/-)-(4bS,8aR,10aS))-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo
      3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile), a potent
      activator of the Keap1/Nrf2/ARE pathway, has the potential to be a first in class
      drug for the treatment of diabetic nephropathy. To identify the protein targets
      for the development of 1, the (1:1)-diasteromeric mixture of biotinylated
      tricycles 3a and 3b were designed and synthesized. For the synthesis of 3a and
      3b, a new important precursor, hydroxylated tricycle (+/-)-16 was synthesized
      from 4 by a C1 alpha-methyl group oxidation protocol, which involves
      cyclopalladation of the C1 alpha-methyl group from a C2-oxime. For the induction
      of the phase 2 cytoprotective enzyme NQO1 in Hepa1c1c7 murine hepatoma cells, the
      diasteromeric mixture 3a and 3b shows high potency (CD, 75 nM) although this
      potency is lower than that of 1 and 16. Thus, biotinylated tricycles 3a and 3b
      may be promising tools for the isolation of the protein targets of 1.

PMID- 24018194
TI  - A bird's-eye view on the modern genetics workflow and its potential applicability
      to the locust problem.
AB  - Genetics is an immense science and the current developments in its methods and
      techniques as well as the fast emerging tools make it one of the most powerful
      biological sciences. Indeed, from taxonomy and ecology to physiology and
      molecular biology, every biological science makes use of genetics techniques and
      methods at one time or another. In fact, development in genetics is such that it
      is now possible to characterize and analyze the expression of the whole set of
      genes of virtually every living organism, even if it is a non-model one. Locusts
      are notorious for the damage they cause to the ecosystems and economies of the
      areas affected by their recurrent population outbreaks. To prevent and deal with
      these outbreaks, we now count on both biological as well as chemical agents that
      are proving to be successful in reducing the damage that otherwise locust
      population outbreaks might cause. However, a better, efficient and
      environmentally friendly solution is still a hoped-for target. In my opinion, the
      ideal future pesticide should be both environmentally friendly, risk free and
      species-specific. To reach the knowledge needed for the development of such
      species-specific anti-locust agent, deep and accurate knowledge of the locusts'
      genetics and molecular biology is a must. Since genes and their expression levels
      lie at the bottom of every biological phenomenon, any species-specific solution
      to the locust problem requires a good knowledge of these organisms' genes as well
      as the quantitative and spatio-temporal dynamics of their expression. To reach
      such knowledge, collaborative work is needed as well as a clear workflow that,
      given the fast development in the genetics tools, is not always clear to all
      research groups. For this reason, here I describe a genetics workflow that should
      allow taking advantage of the most recent genetics tools and techniques to answer
      question relating to locust biology. My hope is that the adoption of this and
      other work strategies by different research groups, especially when the work is a
      collaborative one, would provide precious information on the biology and the
      biological phenomena that these economically important organisms exhibit. 

PMID- 24018195
TI  - The effects of thermal and high-CO2 stresses on the metabolism and surrounding
      microenvironment of the coral Galaxea fascicularis.
AB  - The effects of elevated temperature and high pCO2 on the metabolism of Galaxea
      fascicularis were studied with oxygen and pH microsensors. Photosynthesis and
      respiration rates were evaluated from the oxygen fluxes from and to the coral
      polyps. High-temperature alone lowered both photosynthetic and respiration rates.
      High pCO2 alone did not significantly affect either photosynthesis or respiration
      rates. Under a combination of high-temperature and high-CO2, the photosynthetic
      rate increased to values close to those of the controls. The same pH in the
      diffusion boundary layer was observed under light in both (400 and 750 ppm) CO2
      treatments, but decreased significantly in the dark as a result of increased CO2.
      The ATP contents decreased with increasing temperature. The effects of
      temperature on the metabolism of corals were stronger than the effects of
      increased CO2. The effects of acidification were minimal without combined
      temperature stress. However, acidification combined with higher temperature may
      affect coral metabolism due to the amplification of diel variations in the
      microenvironment surrounding the coral and the decrease in ATP contents.

PMID- 24018196
TI  - Potential ultrastructural changes in rat epididymal cell types induced by
      Boswellia papyrifera and Boswellia carterii incense.
AB  - Boswellia papyrifera and Boswellia carterii, known as Arabian incense, diffuses
      smoke, contaminating the air, which adversely affects human health. Therefore,
      this study was designed to ascertain the effect of these plants on
      histopathological and ultrastructure changes in cauda epididymis of Albino rats.
      Animals were exposed to 4 g/kg body weight of B. papyrifera and B. carterii daily
      for 120 days along with suitable controls. Our study indicates a significant
      reduction in epithelial heights. Cells showed signs of degeneration. The
      ultrastructural study revealed that the cauda epididymis was affected, including
      its cell types. Furthermore, a decrease in the size of mitochondria, Golgi
      complex, and both ERs was observed. In all treated groups, plasma fructose
      decreased considerably, indicating the sign of reduced energy, vital for motility
      and other sperm functions. The results of this study suggest that these plants
      systematically affect cauda epididymal cell types and its lumen through its
      potential toxicity.

PMID- 24018197
TI  - Leaf colleters in Tontelea micrantha (Celastraceae, Salacioideae): ecological,
      morphological and structural aspects.
AB  - The colleter secretion can be useful to protect plants of Cerrado (Brazilian
      savanna) biome during the long and pronounced dry season. This study describes
      the presence of colleters in Tontelea micrantha and represents the first record
      of these structures in Celastraceae. To investigate colleter structure and their
      secretory processes, young leaves were collected, fixed, and processed according
      to conventional techniques for light, and electron microscopy. Colleters were
      observed at the marginal teeth on the leaf. They produce mucilaginous secretions
      that spread over the leaf surface. After secretory phase, colleters abscise. The
      secretory epithelium is uniseriate and composed of elongated cells whose dense
      cytoplasm is rich in organelles. The ultrastructure of the secretory cells is
      compatible with the pectin-rich secretion. Observations of the young leaves
      surface revealed the presence of superficial hydrophilic secretion films that
      appeared to have the function of maintaining the water status of those organs. 

PMID- 24018198
TI  - Valorization of solid olive mill wastes by cultivation of a local strain of
      edible mushrooms.
AB  - Olive oil industry generates huge quantities of solid olive mill wastes (SOMW),
      causing environmental damage. Cultivation of edible mushrooms, such as Pleurotus
      ostreatus is a valuable approach for SOMW valorization. A local strain mycelium
      (Tizi-Ouzou, Algeria) of P. ostreatus (LPO) was isolated from castor oil plants.
      Oyster mushroom spawn, produced on barley grains, was used to inoculate wet SOMW,
      steamed in a traditional steamer during 45 min. The mycelium growth rate on SOMW
      was first estimated in Petri dish by measuring the surface colonized by the
      mycelium. The fruit body yields were estimated on culture bags containing 2 kg
      each of SOMW inoculated at 7% (w/w). The local strain potential was compared with
      that of a commercial one. Both strains produced high-quality mushrooms, but with
      low yields. The supplementation of the SOMW with wheat straw at the rate of 10%
      and 2% of CaCO3 had significantly enhanced the productivity of the two strains,
      multiplying it by 3.2 for LPO and by 2.6 for CPO. 

PMID- 24018199
TI  - Distribution of endemic and alien plants along Mediterranean rivers: a useful
      tool to identify areas in need of protection?
AB  - The main aim was to obtain information about the more critical sectors of
      Mediterranean-type rivers, especially in the islands where the percentage of
      endemic species is high, even in riparian habitats. Our hypothesis was that
      endemic and alien species, considered important in defining conservation
      priorities along rivers, have different patterns of distribution and their
      coexistence indicates human impacts on fluvial systems, which can cause natural
      habitat loss. Generalized Additive Models were used to model the distribution
      patterns of endemic and alien species along the longitudinal gradient. They
      showed that endemic species were linked to the most natural areas in the middle
      and upper sections of the rivers, whereas the distribution of aliens in middle
      and lower sections can be regarded as a consequence of human impact. This finding
      underlined the presence in the middle sections of the rivers of areas with
      important floristic features that are also affected by alien species. What
      currently seems a situation of equilibrium turns out to call for careful control,
      first and foremost, by maintaining riparian vegetation. Our results highlighted
      the utility of our method for rapidly obtaining information about the
      criticalities of rivers in Mediterranean biodiversity hotspots. 

PMID- 24018200
TI  - Nurses' foot care activities in home health care.
AB  - This study described the basic foot care activities performed by nurses and
      factors associated with these in the home care of older people. Data were
      collected from nurses (n=322) working in nine public home care agencies in
      Finland using the Nurses' Foot Care Activities Questionnaire (NFAQ). Data were
      analyzed statistically using descriptive statistics and multivariate liner
      models. Although some of the basic foot care activities of nurses reported using
      were outdated, the majority of foot care activities were consistent with
      recommendations in foot care literature. Longer working experience, referring
      patients with foot problems to a podiatrist and physiotherapist, and patient
      education in wart and nail care were associated with a high score for adequate
      foot care activities. Continuing education should focus on updating basic foot
      care activities and increasing the use of evidence-based foot care methods. Also,
      geriatric nursing research should focus in intervention research to improve the
      use of evidence-based basic foot care activities.

PMID- 24018201
TI  - Modelling cell turnover in a complex tissue during development.
AB  - The growth of organs results from proliferation within distinct cellular
      compartments. Organ development also involves transitions between cell types and
      variations in cell cycle duration as development progresses, and is regulated by
      a balance between entry into the compartment, proliferation of cells within the
      compartment, acquisition of quiescence and exit from that cell state via
      differentiation or death. While it is important to understand how environmental
      or genetic alterations can perturb such development, most approaches employed to
      date are descriptive rather than quantitative. This is because the identification
      and quantification of such parameters, while tractable in vitro, is challenging
      in the context of a complex tissue in vivo. Here we present a new framework for
      determining cell turnover in developing organs in vivo that combines cumulative
      cell-labelling and quantification of distinct cell-cycle phases without assuming
      homogeneity of behaviour within that compartment. A mathematical model is given
      that allows the calculation of cell cycle length in the context of a specific
      biological example and assesses the uncertainty of this calculation due to
      incomplete knowledge of cell cycle dynamics. This includes the development of a
      two population model to quantify possible heterogeneity of cell cycle length
      within a compartment and estimate the aggregate proliferation rate. These models
      are demonstrated on data collected from a progenitor cell compartment within the
      developing mouse kidney, the cap mesenchyme. This tissue was labelled by
      cumulative infusion, volumetrically quantified across time, and temporally
      analysed for the proportion of cells undergoing proliferation. By combining the
      cell cycle length predicted by the model with measurements of total cell
      population and mitotic rate, this approach facilitates the quantification of exit
      from this compartment without the need for a direct marker of that event. As a
      method specifically designed with assumptions appropriate to developing organs we
      believe this approach will be applicable to a range of developmental systems,
      facilitating estimations of cell cycle length and compartment behaviour that
      extend beyond simple comparisons of mitotic rates between normal and perturbed
      states. 

PMID- 24018202
TI  - Mechanisms underlying the additive and redundant Qrr phenotypes in Vibrio harveyi
      and Vibrio cholerae.
AB  - Vibrio harveyi and Vibrio cholerae regulate their virulence factors according to
      the local cell-population density in a regulatory system called quorum sensing.
      Their quorum sensing systems contain a small RNA (sRNA) circuit to regulate
      expression of a master transcriptional regulator via multiple quorum regulated
      RNA (Qrr) and a protein chaperon Hfq. Experiments and genetic analysis show that
      their respective quorum sensing networks are topologically equivalent and have
      homologous components, yet they respond differently to the same experimental
      conditions. In particular, V. harveyi Qrr are additive because all of its Qrr are
      required to maintain wild-type-like repression of its master transcriptional
      regulator. Conversely, V. cholerae Qrr are redundant because any of its Qrr is
      sufficient to repress its master transcriptional regulator. Given the striking
      similarities between their quorum sensing systems, experimentalists have been
      unable to identify conclusively the mechanisms behind these phenotypic
      differences. Nevertheless, the current hypothesis in the literature is that
      dosage compensation is the mechanism underlying redundancy. In this work, we
      identify the mechanisms underlying Qrr redundancy using a detailed mathematical
      model of the V. harveyi and V. cholerae sRNA circuits. We show that there are
      exactly two different cases underlying Qrr redundancy and that dosage
      compensation is unnecessary and insufficient to explain Qrr redundancy. Although
      V. harveyi Qrr are additive when the perturbations in Qrr are large, we predict
      that V. harveyi and V. cholerae Qrr are redundant when the perturbations in Qrr
      are small. We argue that the additive and redundant Qrr phenotypes can emerge
      from parametric differences in the sRNA circuit. In particular, we find that the
      affinity of Qrr and its expression relative to the master transcriptional
      regulator determine the level of redundancy in V. harveyi and V. cholerae.
      Furthermore, the additive and redundant Qrr phenotypes reflect differences in the
      concentration of Hfq-Qrr in V. harveyi and V. cholerae. We use our model to test
      the dosage compensation hypothesis and show that decreasing the expression of
      qrr, rather than removing dosage compensation, abolishes Qrr redundancy in V.
      cholerae. Further experimentation is needed to test our results and both Qrr
      redundancy hypotheses. 

PMID- 24018203
TI  - Orthographic projection capillary array fluorescent sensor for mHealth.
AB  - To overcome the limited sensitivity of phone cameras for mobile health (mHealth)
      fluorescent detection, we have previously developed a capillary array which
      enables a ~100 * increase in detection sensitivity. However, for an effective
      detection platform, the optical configuration must allow for uniform measurement
      sensitivity between channels when using such a capillary array sensor. This is a
      challenge due to the parallax inherent in imaging long parallel capillary tubes
      with typical lens configurations. To enable effective detection, we have
      developed an orthographic projection system in this work which forms parallel
      light projection images from the capillaries using an object-space telecentric
      lens configuration. This optical configuration results in a significantly higher
      degree of uniformity in measurement between channels, as well as a significantly
      reduced focal distance, which enables a more compact sensor. A plano-convex lens
      (f=150 mm) was shown to produce a uniform orthographic projection when properly
      combined with the phone camera's built in lens (f=4mm), enabling measurements of
      long capillaries (125 mm) to be made from a distance of 160 mm. The number of
      parallel measurements which can be made is determined by the size of the
      secondary lens. Based on these results, a more compact configuration with shorter
      32 mm capillaries and a plano-convex lens with a shorter focal length (f=10mm)
      was constructed. This optical system was used to measure serial dilutions of
      fluorescein with a limit of detection (LOD) of 10nM, similar to the LOD of a
      commercial plate reader. However, many plate readers based on standard 96 well
      plate requires sample volumes of 100 MUl for measurement, while the capillary
      array requires a sample volume of less than 10 MUl. This optical configuration
      allows for a device to make use of the ~100 * increase in fluorescent detection
      sensitivity produced by capillary amplification while maintaining a compact size
      and capability to analyze extremely small sample volumes. Such a device based on
      a phone or other optical mHealth technology will have the sensitivity of a
      conventional plate reader but have greater mHealth clinical utility, especially
      for telemedicine and for resource-poor settings and global health applications.

PMID- 24018204
TI  - Construction of Specific Parallel Amplification of RNA Ends (SPARE) libraries for
      the systematic identification of plant microRNA processing intermediates.
AB  - MicroRNAs (miRNAs) are small RNAs that derive from endogenous precursors
      harboring foldback structures. Plant miRNA precursors are quite variable in their
      size and shape. Still, the miRNA processing machinery, consisting of DICER-LIKE1
      (DCL1) and accessory proteins recognize structural features on the precursors to
      cleave them at specific places releasing the mature miRNAs. The identification of
      miRNA processing intermediates in plants has mostly relied on a modified 5' RACE
      method, designed to detect the 5' end of uncapped RNAs. However, this method is
      time consuming and is, therefore, only practical for the analysis of a handful
      miRNAs. Here, we present a modification of this approach in order to perform
      genome-wide analysis of miRNA processing intermediates. Briefly, a reverse
      transcription is performed with a mixture of specific primers designed against
      all known miRNA precursors. miRNA processing intermediates are then specifically
      amplified to generate a library and subjected to deep sequencing. This method,
      called SPARE (Specific Parallel Amplification of 5' RNA Ends) allows the
      identification of processing intermediates for most of the Arabidopsis miRNAs.
      The results enable the determination of the DCL1 processing direction and the
      cleavage sites introduced by miRNA processing machinery in the precursors. The
      SPARE method can be easily adapted to detect miRNA-processing intermediates in
      other systems. 

PMID- 24018205
TI  - How are palliative care cancer populations characterized in randomized controlled
      trials? A literature review.
AB  - CONTEXT: The difficulties in defining a palliative care patient accentuate the
      need to provide stringent descriptions of the patient population in palliative
      care research. OBJECTIVES: To conduct a systematic literature review with the aim
      of identifying which key variables have been used to describe adult palliative
      care cancer populations in randomized controlled trials (RCTs). METHODS: The data
      sources used were MEDLINE (1950 to January 25, 2010) and Embase (1980 to January
      25, 2010), limited to RCTs in adult cancer patients with incurable disease. Forty
      three variables were systematically extracted from the eligible articles.
      RESULTS: The review includes 336 articles reporting RCTs in palliative care
      cancer patients. Age (98%), gender (90%), cancer diagnosis (89%), performance
      status (45%), and survival (45%) were the most frequently reported variables. A
      large number of other variables were much less frequently reported. CONCLUSION: A
      substantial variation exists in how palliative care cancer populations are
      described in RCTs. Few variables are consistently registered and reported. There
      is a clear need to standardize the reporting. The results from this work will
      serve as the basis for an international Delphi process with the aim of reaching
      consensus on a minimum set of descriptors to characterize a palliative care
      cancer population.

PMID- 24018207
TI  - The activity of palliative care team pharmacists in designated cancer hospitals:
      a nationwide survey in Japan.
AB  - CONTEXT: The role of pharmacists in palliative care has become more important now
      that they are able to provide medication review, patient education, and advice to
      physicians about a patient's pharmacotherapy. However, there is little known
      about pharmacists' activity on palliative care teams. OBJECTIVES: The present
      study aimed to examine the clinical, educational, and research activities of
      pharmacists on palliative care teams and pharmacist-perceived contributions to a
      palliative care team or why they could not contribute. METHODS: We sent 397
      questionnaires to designated cancer hospitals, and 304 responses were analyzed
      (response rate 77%). RESULTS: Of the pharmacists surveyed, 79% and 94% reported
      attending ward rounds and conferences, respectively. Half of the pharmacists
      provided information/suggestions to the team about pharmacology, pharmaceutical
      production, managing adverse effects, drug interactions, and/or rotation of
      drugs. In addition, 80% of the pharmacists organized a multidisciplinary
      conference on palliative care education. Furthermore, 60% of the pharmacists
      reported on palliative care research to a scientific society. Seventy percent of
      the pharmacists reported some level of contribution to a palliative care team,
      whereas 16% reported that they did not contribute, with the main perceived
      reasons for no contribution listed as insufficient time (90%) and/or staff (68%).
      CONCLUSION: In Japan, pharmacists exercise a moderate level of clinical activity
      on palliative care teams. Many pharmacists believe that they contribute to such a
      team and generally place more emphasis on their educational and research roles
      compared with clinical work.

PMID- 24018206
TI  - Web-based symptom management for women with recurrent ovarian cancer: a pilot
      randomized controlled trial of the WRITE Symptoms intervention.
AB  - CONTEXT: Little research has focused on symptom management among women with
      ovarian cancer. Written Representational Intervention To Ease Symptoms (WRITE
      Symptoms) is an educational intervention delivered through asynchronous web-based
      message boards between a study participant and a nurse. OBJECTIVES: We evaluated
      WRITE Symptoms for 1) feasibility of conducting the study via message boards, 2)
      system usability, 3) participant satisfaction, and 4) initial efficacy. METHODS:
      Participants were 65 women (mean age, 56.5; SD = 9.23) with recurrent ovarian
      cancer randomized using minimization with race/ethnicity (non-Hispanic white vs.
      minority) as the stratification factor. Measures were obtained at baseline and
      two and six weeks after intervention. Outcomes were feasibility of conducting the
      study, system usability, participant satisfaction, and efficacy (symptom
      severity, distress, consequences, and controllability). RESULTS: Fifty-six
      (87.5%) participants were retained, and the mean usability score (range 1-7) was
      6.18 (SD = 1.29). All satisfaction items were scored at 5 (of 7) or higher. There
      were significant between-group effects at T2 for symptom distress, with those in
      the WRITE Symptoms group reporting lower distress than those in the control group
      [t(88.4) = -2.57; P = 0.012], with a similar trend for symptom severity [t(40.4)
      = -1.95; P = 0.058]. Repeated measures analysis also supported a group effect,
      with those in the WRITE Symptoms group reporting lower symptom distress than
      those in the control condition [F(1, 56.7) = 4.59; P = 0.037]. CONCLUSION:
      Participants found the intervention and assessment system easy to use and had
      high levels of satisfaction. Initial efficacy was supported by decreases in
      symptom severity and distress.

PMID- 24018208
TI  - The role of Sp1 and EZH2 in the regulation of LMX1A in cervical cancer cells.
AB  - We have reported previously that LIM homeobox transcription factor 1alpha (LMX1A)
      is hypermethylated and functions as a metastasis suppressor in cervical cancer
      cells. However, the regulation of LMX1A in carcinogenesis has not been reported.
      We aim to clarify whether specificity protein 1 (Sp1) and enhancer of zeste
      homolog 2 (EZH2) are involved in the regulation of LMX1A in cervical cancer.
      First we characterized the LMX1A promoter and used overexpression, knockdown, and
      reporter assays to show that Sp1 increased LMX1A promoter activity. Next, we used
      site-directed mutagenesis and electrophoresis mobility shift assays (EMSAs) to
      demonstrate that Sp1-binding sites were important for Sp1-mediated activation of
      the LMX1A promoter. Chromatin immunoprecipitation data demonstrated that Sp1
      could bind directly to the LMX1A promoter and activate endogenous LMX1A
      expression in cells pretreated with 5-aza-2'-deoxycytidine (5-aza-dC). Knockdown
      of EZH2 decreased H3K27me3 histone modification but was insufficient to restore
      LMX1A expression. To explore the effect of EZH2 on the endogenous LMX1A promoter,
      we treated EZH2-knockdown cells with 5-aza-dC and trichostatin A (TSA) and then
      depleted the cells of drugs for 3days. H3K14ac was enriched at the LMX1A promoter
      in EZH2-knockdown cells and LMX1A mRNA was still expressed. Taken together, these
      data imply that Sp1 may activate LMX1A expression upon oncogenic stress during
      cervical cancer development. Moreover, suppression of EZH2 may delay resilencing
      of LMX1A after the removal of 5-aza-dC and TSA. 

PMID- 24018209
TI  - SUMO-targeted ubiquitin ligases.
AB  - Covalent posttranslational modification with SUMO (small ubiquitin-related
      modifier) modulates functions of a wide range of proteins in eukaryotic cells.
      Sumoylation affects the activity, interaction properties, subcellular
      localization and the stability of its substrate proteins. The recent discovery of
      a novel class of ubiquitin ligases (E3), termed ULS (E3-S) or STUbL, that
      recognize sumoylated proteins, links SUMO modification to the
      ubiquitin/proteasome system. Here we review recent insights into the properties
      and function of these ligases and their roles in regulating sumoylated proteins.
      This article is part of a Special Issue entitled: Ubiquitin-Proteasome System.
      Guest Editors: Thomas Sommer and Dieter H. Wolf. 

PMID- 24018210
TI  - Molecular genotyping of Echinococcus granulosus from dromedaries (Camelus
      dromedarius) in eastern Iran.
AB  - With the aim of genotyping Echinococcus granulosus cysts found in Iranian
      dromedaries (Camelus dromedarius), 50 cysts of E. granulosus were collected from
      five geographical regions in Iran. Cysts were characterized using polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of
      the internal transcribed spacer 1 (ITS1) gene and sequencing fragments of the
      genes coding for mitochondrial cytochrome c oxidase subunit 1 (cox1).
      Morphological criteria using rostellar hook dimensions were also undertaken. The
      present results have shown that 27 out of 50 E. granulosus cysts (54%) were
      determined as the G1 strain, and the other (46%) were determined as the G6
      strain. The molecular analysis of the ITS1 region of ribosomal DNA corresponded
      with the morphological findings. Because of its recognized infectivity in humans,
      the G1 genotype is a direct threat to human health and its presence in Iranian
      dromedaries is of urgent public health importance. 

PMID- 24018211
TI  - Spanish evidence-based guidelines on the treatment of psoriasis with biologic
      agents, 2013. Part 1: on efficacy and choice of treatment. Spanish Psoriasis
      Group of the Spanish Academy of Dermatology and Venereology.
AB  - Biologic therapy is a well-established strategy for managing moderate and severe
      psoriasis. Nevertheless, the high cost of such therapy, the relatively short span
      of clinical experience with biologics, and the abundance of literature now
      available on these agents have made evidence-based and consensus-based clinical
      guidelines necessary. The ideal goal of psoriasis treatment is to achieve
      complete or nearly complete clearing of lesions and to maintain it over time.
      Failing that ideal, the goal would be to reduce involvement to localized lesions
      that can be controlled with topical therapy. Although current evidence allows us
      to directly or indirectly compare the efficacy or risk of primary or secondary
      failure of available biologics based on objective outcomes, clinical trial
      findings cannot be directly translated to routine practice. As a result, the
      prescribing physician must tailor the treatment regimen to the individual
      patient. This update of the clinical practice guidelines issued by the Spanish
      Academy of Dermatology and Venereology (AEDV) on biologic therapy for psoriasis
      incorporates information from the most recent publications on this topic. 

PMID- 24018212
TI  - Different mutations at V363 MAPT codon are associated with atypical clinical
      phenotypes and show unusual structural and functional features.
AB  - Microtubule-associated protein tau gene (MAPT) is one of the major genes linked
      to frontotemporal lobar degeneration, a group of neurodegenerative diseases
      clinically, pathologically, and genetically heterogeneous. In particular, MAPT
      mutations give rise to the subgroup of tauopathies. The pathogenetic mechanisms
      underlying the MAPT mutations so far described are the decreased ability of tau
      protein to promote microtubule polymerization (missense mutations) or the altered
      ratio of tau isoforms (splicing mutations), both leading to accumulation of
      hyperphosphorylated filamentous tau protein. Following a genetic screening of
      patients affected by frontotemporal lobar degeneration, we identified 2 MAPT
      mutations, V363I and V363A, leading to atypical clinical phenotypes, such as
      posterior cortical atrophy. We investigated in vitro features of the recombinant
      mutated tau isoforms and revealed unusual functional and structural
      characteristics such as an increased ability to promote microtubule
      polymerization and a tendency to form oligomeric instead of filamentous
      aggregates. Thus, we disclosed a greater than expected complexity of abnormal
      features of mutated tau isoforms. Overall our findings suggest a high probability
      that these mutations are pathogenic.

PMID- 24018213
TI  - Missense variants in CR1 are associated with increased risk of Alzheimer' disease
      in Han Chinese.
AB  - Complement receptor 1 (CR1) has been considered to play an important role in late
      onset Alzheimer's disease (LOAD) pathogenesis. To explore the correlation between
      the CR1 gene and LOAD, a 2-step design study was conducted in our Northern Han
      Chinese population. We first sequenced the promoter, exons, the 5' and 3'
      untranslated regions and exon-intron boundaries of CR1 in a small sample (n =
      100). This allowed us to identify a total of 22 variants. In addition, 6 missense
      variants within the CR1 gene were selected to be genotyped in a total of 2292
      individuals. Only 2 SNPs (rs116806486, Thr->Ala; rs6691117, Ile->Val) were
      significantly associated with an increased risk of LOAD. After stratification by
      APOE epsilon4-carrying status, significance was observed in APOE epsilon4 non
      carriers for rs116806486 and in APOE epsilon4 carriers for rs6691117. Logistic
      analysis revealed that the rs116806486 polymorphism remained associated with LOAD
      in a dominant model, whereas the rs6691117 polymorphism was associated with LOAD
      in additive and recessive models but not in a dominant model after adjusting for
      sex, age at onset, and APOE epsilon4 status. Examination of the haplotypes
      identified the risk of a 3-SNP (rs2274567, rs3737002, and rs6691117) haplotype
      "ATG" in CR1 was associated with an increased risk for LOAD. These findings
      provide the evidence that missense variants in the CR1 gene may be involved in
      LOAD pathologic process in Han Chinese.

PMID- 24018214
TI  - Porcine xenografts vs. (cryopreserved) allografts in the management of partial
      thickness burns: is there a clinical difference?
AB  - Porcine xenografts and cryopreserved allografts are used for the management of
      partial thickness burns and both biological materials have strong advocates with
      regard to clinical performance, the possibility of disease transfer from donor to
      recipient and other clinical aspects. A literature analysis was performed in an
      attempt to investigate whether true (statistically significant) differences exist
      on clinical performance and on other determinants for use. Comparing the results
      of this study with a similar, previously published study performed on possible
      differences amongst different types of allograft in the management of partial
      thickness burns, both allografts and porcine xenograft seem to perform equally
      well clinically with regard to healing related outcomes. In addition, the risk of
      disease transfer, in real life, was shown to be minimal. Consequently, clinical
      aspects being equal, other aspects such as price and availability should be used
      to decide which material to use for the management of partial thickness burns. 

PMID- 24018215
TI  - The infection risk of plastic wrap as an acute burns dressing.
AB  - BACKGROUND: Domestic plastic wrap has been recommended as an appropriate acute
      burn wound dressing in the Emergency Management of Severe Burns course. There
      remain limited studies reporting the risk of infection associated with this
      dressing. AIM: To determine the potential infection risk of domestic plastic wrap
      used to treat acute burns wounds by assessment for the presence of clinically
      significant micro-organisms. METHODS: Ten plastic wrap samples were collected
      from a roll that had been opened for several months on the burns ward at our
      institution. Plastic wrap was imprinted directly onto horse-blood agar plates.
      The plates were incubated for 72h in aerobic conditions with 5% CO2. RESULTS: We
      found no significant growth on any agar plate after incubation. A sufficient
      amount of plastic wrap was sampled to be confident that areas up to 12cm*12cm
      from the centre of the plastic sheet were aerobically sterile. CONCLUSIONS: Our
      data suggest that the potential for plastic wrap to act as a fomite when used as
      an acute burn wound dressing is extremely low.

PMID- 24018216
TI  - Clinical application and viability of cryopreserved cadaveric skin allografts in
      severe burn: a retrospective analysis.
AB  - INTRODUCTION: Cadaveric cutaneous allografts are used in burns surgery both as a
      temporary bio-dressing and occasionally as definitive management of partial
      thickness burns. Nonetheless, limitations in the understanding of the biology of
      these grafts have meant that their role in burns surgery continues to be
      controversial. METHODS: A review of all patients suffering 20% or greater total
      body surface area (TBSA) burns over an eight year period that received cadaveric
      allografts were identified. To investigate whether tissue viability plays a role
      in engraftment success, five samples of cryopreserved cadaveric cutaneous
      allograft processed at the Donor Tissue Bank of Victoria (DTBV) were submitted to
      our laboratory for viability analysis using two methods of Trypan Blue Exclusion
      and tetrazolium salt (MTT) assays. RESULTS: During the study period, 36 patients
      received cadaveric allograft at our institution. The average total burn surface
      area (TBSA) for this group of patients was 40% and all patients received
      cadaveric skin as a temporizing measure prior to definitive grafting. Cadaveric
      allograft was used in complicated cases such as wound contamination, where
      synthetic dressings had failed. Viability tests showed fewer than 30% viability
      in processed allografts when compared to fresh skin following the thawing
      process. However, the skin structure in the frozen allografts was histologically
      well preserved. CONCLUSION: Cryopreserved cutaneous cadaveric allograft has a
      positive and definite role as an adjunct to conventional dressing and grafting
      where available, particularly in patients with large TBSA burns. The low
      viability of cryopreserved specimens processed at DTBV suggests that cell
      viability in cadaveric allograft may not be essential for its clinical function
      as a wound dressing or even as permanent dermal substitute.

PMID- 24018217
TI  - A 2 year experience of nurse led conscious sedation in paediatric burns.
AB  - INTRODUCTION: Ketamine and midazolam have been used safely by anaesthetists in
      paediatric burns and have a good safety profile. We believed that this could be
      developed to a nurse led conscious sedation protocol, without direct anaesthetic
      attendance. METHODS: Two years experience of our technique was retrospectively
      reviewed. We recorded the age, weight, percentage burn, dose of oral ketamine and
      midazolam given, time for procedure whether an anaesthetist was called to the
      sedation room, and the reason for the call. RESULTS: Data were collected for a
      total of 45 children undergoing 131 procedures. The age (mean +/- SD) was 9.5 +/-
      4.7 years, the weight (mean +/- SD) 38.7 +/- 19.8 kg and the percentage burn
      (mean +/- SD) was 25.3 +/- 22.9%. The dose of oral ketamine (mean +/- SD) was
      409.5 +/- 252.3mg or 8.78 +/- 3.27 mg/kg and the dose of oral midazolam (mean +/-
      SD) was 17.6 +/- 8.7 mg or 0.44 +/- 0.14 mg/kg. The duration of procedure (mean
      +/- SD) was 97.32 +/- 32.90 min. The incidence of the anaesthetist required to
      administer further sedation was 29.8% of sedations. The decision to convert to
      general anaesthesia was taken in 2.3% of cases. An anaesthetist was called other
      than to top up sedation in 6.9% of sedations. CONCLUSION: Our protocol for nurse
      monitored conscious sedation using oral ketamine and midazolam in the burns
      patient provides a safe method of analgesic sedation for burn dressing changes.

PMID- 24018219
TI  - Emerging adulthood themes, role transitions and substance use among Hispanics in
      Southern California.
AB  - INTRODUCTION: Hispanic emerging adults appear to be at especially high risk for
      substance use but little is known about their risk and protective factors. A
      crucial next step to reducing substance use among this priority population may
      involve understanding how transition-to-adulthood themes are associated with
      substance use. Intervention and prevention programs could also benefit from
      information about which if any specific transitions undergone in emerging
      adulthood are associated with substance use. METHODS: Hispanic emerging adults
      (aged 18 to 24) completed surveys indicating their identification with transition
      to-adulthood themes, role transitions in the past year, and use of alcohol and
      marijuana. Logistic regression models were used to examine the associations
      between transition-to-adulthood themes and past-month binge drinking and
      marijuana use, controlling for age and gender. Separate logistic regression
      models explored the association between each individual role transition and past
      month binge drinking and marijuana use, controlling for age and gender and using
      a Bonferonni correction. RESULTS: Among the participants (n=1,390), 41% were
      male, the average age was 21, 24% reported past-month marijuana use and 34%
      reported past-month binge drinking. Participants who felt emerging adulthood was
      a time of focusing on others were less likely to report marijuana use and binge
      drinking. Among the 24 transitions, five were significantly associated with past
      month marijuana use and 10 were significantly associated with past-month binge
      drinking. CONCLUSION: Findings suggest transition-to-adulthood themes as well as
      specific changes experienced by emerging adults are meaningful for Hispanics and
      should be explored in prevention and intervention programs in the future. Future
      research should determine what specific mechanisms are making these transitional
      processes risk factors for substance use.

PMID- 24018220
TI  - Re-examining the price sensitivity of demand for cigarettes with quantile
      regression.
AB  - Existing studies suggest that teenagers, young adults, and individuals of low
      socioeconomic status are more sensitive to changes in cigarette prices. However,
      little is known as to whether there are differences in price sensitivity between
      heavy and light smokers. To examine this gap, the present study uses quantile
      regression to estimate price sensitivity of demand for smokers with different
      levels of tobacco consumption. We conducted a national personal interview survey
      in Taiwan and the results showed price sensitivity is positively associated with
      the level of cigarette consumption. The data indicate that pricing strategies are
      more likely to notably reduce cigarette consumption for heavy smokers. Our
      findings suggest policymakers can meet target control for cigarette consumption
      by effectively adjusting market prices of cigarettes. 

PMID- 24018218
TI  - Changing appetites: the adaptive advantages of fuel choice.
AB  - Cells are capable of metabolizing a variety of carbon substrates, including
      glucose, fatty acids, ketone bodies, and amino acids. Cellular fuel choice not
      only fulfills specific biosynthetic needs, but also enables programmatic
      adaptations to stress conditions beyond compensating for changes in nutrient
      availability. Emerging evidence indicates that specific switches from utilization
      of one substrate to another can have protective or permissive roles in disease
      pathogenesis. Understanding the molecular determinants of cellular fuel
      preference may provide insights into the homeostatic control of stress responses,
      and unveil therapeutic targets. Here, we highlight overarching themes
      encompassing cellular fuel choice; its link to cell fate and function; its
      advantages in stress protection; and its contribution to metabolic dependencies
      and maladaptations in pathological conditions. 

PMID- 24018221
TI  - Goal-related outcome after acute alcohol-pancreatitis -- a two-year follow-up
      study.
AB  - The aim of this study was to find out if an acute pancreatitis leads the patients
      to reduce their alcohol consumption and if there are factors predicting the
      outcome. We also observed which factors affected the choice of patient's personal
      drinking goal, e.g., abstinence or moderate drinking, how this goal changed
      during the follow-up and how the goal affected the change in drinking habits. In
      2001-2005, 120 patients treated in Tampere University Hospital for their first
      alcohol-related acute pancreatitis were interviewed before discharge from the
      hospital and at the two-year follow-up. All patients had at least one
      intervention session for their alcohol use. Of the patients 87 (72.5%) completed
      the study. The alcohol consumption level and its changes, personal drinking goal
      of the patients, the factors affecting the choice and the changes of the goal
      were observed. Most (96.4%) of the patients were willing to reduce their
      drinking. At follow-up, 34 (40.5%) patients succeeded in reducing their alcohol
      consumption under the pre-set moderate drinking level. The only factor predicting
      alcohol use was the number of hospitalization days due to the acute alcohol
      related pancreatitis (p=0.015). Those who chose abstinence seemed to succeed more
      often in stopping drinking or reducing their drinking below risk levels as
      compared to those with moderation goal (47.9% vs. 28.6%, p=0.075). The only
      abstinence-goal predicting factor was the concern of the relatives, friends or
      doctors (p=0.001). All 6 patients who needed intensive care chose abstinence
      goal. During the follow-up period the goal changed. At baseline, the majority
      chose abstinence but two years after pancreatitis, the majority was striving for
      moderate drinking. A serious illness seems to be a good opportunity to change and
      to motivate patients. Even if abstinence is recommended to patients with alcohol
      related pancreatitis, communication of individual goals is important in the
      motivation process of the patients. 

PMID- 24018222
TI  - The influence of depressed mood on action tendencies toward alcohol: the
      moderational role of drinking motives.
AB  - BACKGROUND: Research suggests that depressed mood is associated with alcohol
      related problems, though its relation with drinking behavior has been
      inconsistent across studies. Efforts to better understand the link between
      depressed mood and alcohol use have examined drinking motives as a potentially
      important moderating variable. The current study sought to examine whether
      drinking motives moderate the influence of depressed mood on alcohol-related
      action tendencies. Based on Baker, Morse, and Sherman's (1986) positive and
      negative reinforcement schema model, two competing moderational hypotheses
      regarding the influence of depressed mood on appetitive responses for alcohol
      were tested. METHODS: One hundred and sixty-nine college student drinkers
      completed assessments of drinking motives and alcohol use. Subjects were exposed
      to a neutral or depressed mood induction followed by a computerized measure of
      action tendencies toward alcohol stimuli. RESULTS: Hierarchical regression
      analyses were conducted to examine whether the influence of depressed mood on
      action tendencies toward alcohol was moderated by drinking motives. Results
      showed that there was a significant interaction between mood induction condition
      and enhancement motives, such that depressed mood appeared to suppress appetitive
      responding toward alcohol among those with higher enhancement motives. In
      contrast, there was no evidence that coping motives moderated the association
      between mood and appetitive response to alcohol. CONCLUSIONS: These results
      suggest that inhibiting affect states associated with one's motivational
      disposition for drinking may result in the devaluation of alcohol. Limitations
      and implications are discussed.

PMID- 24018223
TI  - The association between smoking bans and nicotine dependence: a longitudinal
      analysis of current smokers in Canada.
AB  - BACKGROUND: While a substantial body of research has examined the effects of
      smoking bans on smoking behavior, little is known about the relationship between
      smoking bans and nicotine dependence. The objective of this study was to examine
      whether home and workplace smoking bans are associated with reduced nicotine
      dependence among continuing smokers. METHODS: We used longitudinal data of 1073
      adult daily smokers from the Canadian National Population Health Survey (2004
      2010). Generalized estimating equations were used to examine the association
      between smoking bans and nicotine dependence. RESULTS: Smokers living in homes
      where smoking is restricted were less likely to be nicotine dependent (OR=0.40,
      95% CI=0.32-0.50) than smokers living in homes with no such smoking restriction.
      Workplace smoking policies had no significant association with nicotine
      dependence (complete ban: OR=0.79, 95% CI=0.56-1.11; partial ban: OR=0.82, 95%
      CI=0.57-1.16). There was some evidence that workplace smoking bans were
      significantly associated with nicotine dependence when single items of the
      Fagerstrom test were considered. CONCLUSIONS: This paper demonstrates that the
      presence of a home smoking ban was associated with lower nicotine dependence
      among continuing smokers. The relationship of workplace bans with nicotine
      dependence was less clear and was contingent on the measure of nicotine
      dependence employed. These findings further confirm the importance of bans on
      smoking in the home, workplace, and other public places on reducing tobacco
      related harms.

PMID- 24018224
TI  - Mindfulness-based relapse prevention with racial and ethnic minority women.
AB  - Racial and ethnic disparities in the treatment of addiction have been
      acknowledged for several years, yet little is known about which empirically
      supported treatments for substance use disorders are more or less effective in
      treating racial and ethnic minority clients. The current study was a secondary
      analysis of a randomized clinical trial of two evidence-based treatments,
      mindfulness-based relapse prevention (MBRP) and relapse prevention (RP), as part
      of a residential addiction treatment program for women referred by the criminal
      justice system (n=70). At 15-week follow-up, regression analyses found that
      racial and ethnic minority women in MBRP, compared to non-Hispanic and racial and
      ethnic minority women in RP, reported significantly fewer drug use days (d=.31)
      and lower addiction severity (d=.65), based on the Addiction Severity Index.
      Although the small sample size is a limitation, the results suggest that MBRP may
      be more efficacious than traditional treatments for racial and ethnic minority
      women. 

PMID- 24018225
TI  - Cannabis dependence, cognitive control and attentional bias for cannabis words.
AB  - One of the characteristics of people suffering from addictive behaviors is the
      tendency to be distracted by drug cues. This attentional bias for drug cues is
      thought to lead to increased craving and drug use, and may draw individuals into
      a vicious cycle of drug addiction. In the current study we developed a Dutch
      version of the cannabis Stroop task and measured attentional bias for cannabis
      words in a group of heavy cannabis users and matched controls. The classical
      Stroop task was used as a global measure of cognitive control and we examined the
      relationship between cognitive control, cannabis-related problems, cannabis
      craving and cannabis attentional bias. Using our version of the cannabis Stroop
      task, a group of heavy cannabis users showed attentional bias to cannabis words,
      whereas a control group of non-users did not. Furthermore, within the group of
      cannabis users, those who were clinically recognized as dependent showed a
      stronger attentional bias than the heavy, non-dependent users. Cannabis users who
      displayed reduced cognitive control (as measured with the classical Stroop task)
      showed increased session-induced craving. Contrary to expectations, however,
      cognitive control did not appear to modulate the relationship between attentional
      bias to cannabis words (cannabis Stroop task) and cannabis dependence. This study
      confirmed the relationship between cannabis dependence and attentional bias and
      extends this by highlighting a moderating role for cognitive control, which may
      make some more vulnerable to craving. 

PMID- 24018227
TI  - Using mobile eye-tracking to assess attention to smoking cues in a naturalized
      environment.
AB  - INTRODUCTION: Attentional bias to drug cues is thought to contribute to
      maintenance of drug-use behavior among chronic drug users. Studies assessing this
      bias traditionally have assessed drug cues that are explicitly presented in a
      laboratory setting. This study tested the use of a mobile eye-tracking procedure
      to assess visual attention to smoking cues by smokers and non-smokers in a more
      naturalized environment. METHODS: A mobile eye-tracker was used to assess the
      number and duration of fixations made to smoking cues located in an office space
      environment by smokers and non-smokers while completing a sham experimental task.
      Smokers completed two sessions, once after 12h of abstinence and once after
      smoking. RESULTS: Results indicated that smokers made significantly more
      fixations to the smoking cues than non-smokers, regardless of smoking condition
      though the mean amount of time spent fixating on the cues did not differ
      significantly. Smokers did not differ in the number of fixations or mean fixation
      duration across the two smoking conditions, suggesting in this sample that a 12-h
      period of abstinence did not make the smoking cues more salient in this context.
      CONCLUSION: This study demonstrates the successful use of mobile eye-tracking to
      assess attentional biases to environmental drug cues. Results suggest that
      smoking cues in the environment are potentially more attention grabbing for
      smokers compared to non-smokers but these cues do not necessarily hold visual
      attention of smokers longer than that of non-smokers.

PMID- 24018226
TI  - Smoking topography and abstinence in adult female smokers.
AB  - Preliminary evidence, within both adults and adolescents, suggests that the
      intensity with which cigarettes are smoked (i.e., smoking topography) is
      predictive of success during a cessation attempt. These reports have also shown
      topography to be superior compared to other variables, such as cigarettes per
      day, in the prediction of abstinence. The possibility that gender may influence
      this predictive relationship has not been evaluated but may be clinically useful
      in tailoring gender-specific interventions. Within the context of a clinical
      trial for smoking cessation among women, adult daily smokers completed a
      laboratory session that included a 1-hour ad libitum smoking period in which
      measures of topography were collected (N=135). Participants were then randomized
      to active medication (nicotine patch vs. varenicline) and abstinence was
      monitored for 4weeks. Among all smoking topography measures and all abstinence
      outcomes, a moderate association was found between longer puff duration and
      greater puff volume and continued smoking during the active 4-week treatment
      phase, but only within the nicotine patch group. Based on the weak topography
      abstinence relationship among female smokers found in the current study, future
      studies should focus on explicit gender comparisons to examine if these
      associations are specific to or more robust in male smokers. 

PMID- 24018228
TI  - Alcohol use and abuse in young adulthood: do self-control and parents'
      perceptions of friends during adolescence modify peer influence? The TRAILS
      study.
AB  - AIMS: To assess the influence of peer alcohol use during adolescence on young
      adults' alcohol use and abuse, and to assess to what extent parents' perception
      of their adolescent child's friends and adolescent's self-control modify this
      influence. METHODS: We analyzed data from the first, third, and fourth wave of a
      population-based prospective cohort study of 2230 adolescents conducted between
      2001 and 2010 (mean ages: 11.1, 16.3, and 19.1, respectively). Alcohol use and
      abuse were measured at T4 by self-report questionnaires and by the Composite
      International Diagnostics Interview (CIDI), respectively. Peer alcohol use, self
      control, and parents' perception of their adolescent child's friends were
      measured at T3. We adjusted for gender, age, socioeconomic-status, parental
      alcohol use, and adolescent baseline alcohol use. RESULTS: Peer alcohol use
      during adolescence was related to young adults' alcohol use and abuse [odds ratio
      (95% confidence interval): 1.31 (1.11-1.54) and 1.50 (1.20-1.87), respectively].
      Neither parents' perception of their adolescent child's friends nor self-control
      modified this relationship. Alcohol abusers were more likely to have low self
      control than alcohol users. No differences were found between alcohol users and
      abusers regarding their parents' perception of their friends and peer alcohol
      use. CONCLUSIONS: Peer alcohol use during adolescence affects young adults'
      alcohol use and abuse. We found that self-control was only related to alcohol
      abuse. Peer influence was not modified by parents' perception of peers or by self
      control. Peer alcohol use and self-control should thus be separate targets in the
      prevention of alcohol use/abuse.

PMID- 24018229
TI  - Patterns of substance use among Argentinean adolescents and analysis of the
      effect of age at first alcohol use on substance use behaviors.
AB  - OBJECTIVE: The present study used an empirically based method to characterize
      substance use in a sample of Argentinean adolescents and analyzed the association
      between age at drinking onset and substance use behaviors. Differences in alcohol
      expectancies and personality traits as a function of different patterns of
      substance use were also explored. METHOD: Data were obtained from 583 adolescents
      aged 13-18years (M=15.01years; SD=1.5years; 59.5% female) from the city of
      Cordoba, Argentina. Alcohol, tobacco, and drug use and age at first alcohol use
      were measured. Personality traits, including extroversion, conscientiousness,
      impulsivity, and aggression, and positive and negative alcohol expectancies were
      assessed. Latent Class Analysis was applied to examine the structure of five co
      occurring substance use behaviors: frequency of alcohol use, quantity of alcohol
      use, prevalence of drunkenness episodes, tobacco use, and drug use. RESULTS:
      Latent Class Analysis revealed five distinct patterns of substance use. The
      classes differed in substance use behaviors, personality traits, and alcohol
      expectancies. Adolescents with early drinking onset were more likely to show
      heavier alcohol use, more drunkenness episodes, and more drug use than
      adolescents with late drinking onset. CONCLUSIONS: Latent Class Analysis allowed
      the detection of groups of adolescents with distinct patterns of substance use.
      These groups exhibited significantly different personality and alcohol expectancy
      profiles, likely representing subgroups who are at greater risk for developing
      alcohol-related problems.

PMID- 24018230
TI  - Are there reciprocal relationships between substance use risk personality
      profiles and alcohol or tobacco use in early adolescence?
AB  - AIM: We examined whether reciprocal relationships were present between the SURPS
      personality profiles and substance use in early adolescence. METHODS:
      Longitudinal data of four-waves of a broader effectiveness study were used from
      1068 early adolescents. RESULTS: Our cross-lagged models indicated that sensation
      seeking and impulsivity show strongest reciprocal associations with substance use
      during early adolescence. In contrast, no reciprocity was present between
      substance use and anxiety sensitivity and only one reciprocal relationship was
      present between substance use and hopelessness. CONCLUSIONS: In trying to prevent
      early adolescents from alcohol and tobacco use, it might be of key importance to
      acknowledge the mutual influence between certain personality profiles and
      substance use. Specifically, sensation seeking and impulsivity are relevant
      during early adolescence and awareness of early adolescents' vulnerability for
      these personality predispositions is warranted.

PMID- 24018231
TI  - Interactive effects of drinking history and impulsivity on college drinking.
AB  - The transition from adolescence into emerging adulthood is a critical
      developmental period for changes in alcohol use and drinking related problems.
      Prior research has identified a number of distinct developmental alcohol use
      trajectories, which appear to be differentially related to young adult drinking
      outcomes. Another correlate of alcohol use in early adulthood is impulsivity. The
      primary aim of this study was to examine the moderating role of impulsivity in
      the relation between patterns of past alcohol use and hazardous drinking during
      the first year of college. Participants (N=452; 49% male; mean age 18.5years; 82%
      Caucasian) completed self-report measures during the first year of college,
      including retrospective alcohol use calendars, current alcohol use and drinking
      problems, and personality. Group-based trajectory modeling was used to identify
      groups with similar adolescent drinking history from retrospective, self-report.
      Four groups were identified: abstainers/very light users, late/moderate users,
      early/moderate users, and steep increase/heavy users. The abstainer/very light
      user group reported the lowest levels of alcohol use and problematic drinking in
      college; the steep increase/heavy use group reported the highest levels of
      alcohol use and problematic drinking. As predicted, the role of personality
      specifically urgency, or emotion-based rash action-was strongest among moderate
      use groups. These findings may be helpful in guiding targeted prevention and
      intervention programs for alcohol use and abuse. 

PMID- 24018233
TI  - Attention-deficit/hyperactivity disorder among chronic methamphetamine users:
      frequency, persistence, and adverse effects on everyday functioning.
AB  - AIMS: Attention-Deficit/Hyperactivity Disorder (ADHD) is widely regarded as a
      common comorbidity of methamphetamine (MA) dependence, but the frequency,
      persistence, and real-world impact of ADHD among MA users are not known. METHODS:
      Four hundred individuals with MA use disorders within 18months of evaluation and
      355 non-MA using comparison subjects completed a comprehensive neuropsychiatric
      research battery, including self-report measures of everyday functioning.
      RESULTS: In logistic regression models adjusting for potential confounds,
      lifetime diagnoses of ADHD as determined by a structured clinical interview were
      significantly more prevalent among the MA participants (21%) versus comparison
      subjects (6%), particularly the hyperactive and combined subtypes. MA use was
      also associated with an increased persistence of combined subtype of ADHD into
      adulthood. Among the MA users, lifetime ADHD diagnoses were uniquely associated
      with greater concurrent risk of declines in instrumental activities of daily
      living, elevated cognitive symptoms in day-to-day life, and unemployment.
      CONCLUSIONS: Findings indicate that ADHD is prevalent among chronic MA users, who
      are at increased risk for persistence of childhood diagnoses of ADHD into their
      adult years. ADHD also appears to play an important role in MA-associated
      disability, indicating that targeted ADHD screening and treatment may help to
      improve real-world outcomes for individuals with MA use disorders.

PMID- 24018234
TI  - One-step purification of soluble recombinant human 6-phosphogluconate
      dehydrogenase from Escherichia coli.
AB  - 6-Phosphogluconate dehydrogenase (6PGD), the third enzyme in the pentose
      phosphate pathway, was recently identified as a novel target in human lung
      cancer. In this report, we present an expression and purification scheme of
      recombinant human 6PGD from Escherichia coli. Using a DE3 derivative strain
      expressing tRNAs for seven rare codons in E. coli called Rosetta2 (DE3), a large
      quantity of soluble human 6PGD can be expressed with an N-terminal histidine tag
      and purified by a one-step purification procedure to near homogeneity without
      denaturants or refolding. Three to seven milligrams of purified protein could be
      obtained from 100 ml of culture. This recombinant human 6PGD follows classic
      Michaelis-Menton saturation kinetics with respect to both substrates NADP(+) and
      6-phosphogluconate. The respective k(cat) and K(m) were comparable to those of
      6PGDs purified from mammalian tissues. Using this purified 6PGD enzyme, we
      devised an endpoint colorimetric assay suitable for high-throughput screening for
      human 6PGD inhibitors.

PMID- 24018232
TI  - Prevalence and correlates of street-obtained buprenorphine use among current and
      former injectors in Baltimore, Maryland.
AB  - OBJECTIVES: There are few systematic assessments of street-obtained buprenorphine
      use from community-based samples in the United States. The objective of this
      study was to characterize the prevalence, correlates, and reasons for street
      obtained buprenorphine use among current and former injection drug users (IDUs)
      in Baltimore, Maryland. METHODS: In 2008, participants of the ALIVE (AIDS Linked
      to the IntraVenous Experience) study, a community-based cohort of IDUs, were
      administered a survey on buprenorphine. Street-obtained buprenorphine represented
      self-reported use of buprenorphine obtained from the street or a friend in the
      prior three months. RESULTS: Six hundred and two respondents were predominantly
      male (65%), African-American (91%), and 30% were HIV-positive. Overall, nine
      percent reported recent street-obtained buprenorphine use, and only 2% reported
      using to get high. Among active opiate users, 23% reported recent use of street
      obtained buprenorphine. Use of buprenorphine prescribed by a physician, injection
      and non-injection drug use, use of street-obtained methadone and prescription
      opiates, homelessness, and opioid withdrawal symptoms were positively associated,
      while methadone treatment, health insurance, outpatient care, and HIV-infection
      were negatively associated with recent street-obtained buprenorphine use in
      univariate analysis. After adjustment, active injection and heroin use were
      positively associated with street-obtained buprenorphine use. Ninety-one percent
      reported using street-obtained buprenorphine to manage withdrawal symptoms.
      CONCLUSIONS: While 9% reported recent street-obtained buprenorphine use, only a
      small minority reported using buprenorphine to get high, with the majority
      reporting use to manage withdrawal symptoms. There is limited evidence of
      diversion of buprenorphine in this sample and efforts to expand buprenorphine
      treatment should continue with further monitoring.

PMID- 24018235
TI  - Out-of-pocket fertility patient expense: data from a multicenter prospective
      infertility cohort.
AB  - PURPOSE: The high costs of fertility care may deter couples from seeking care.
      Urologists often are asked about the costs of these treatments. To our knowledge
      previous studies have not addressed the direct out-of-pocket costs to couples. We
      characterized these expenses in patients seeking fertility care. MATERIALS AND
      METHODS: Couples were prospectively recruited from 8 community and academic
      reproductive endocrinology clinics. Each participating couple completed face-to
      face or telephone interviews and cost diaries at study enrollment, and 4, 10 and
      18 months of care. We determined overall out-of-pocket costs, in addition to
      relationships between out-of-pocket costs and treatment type, clinical outcomes
      and socioeconomic characteristics on multivariate linear regression analysis.
      RESULTS: A total of 332 couples completed cost diaries and had data available on
      treatment and outcomes. Average age was 36.8 and 35.6 years in men and women,
      respectively. Of this cohort 19% received noncycle based therapy, 4% used
      ovulation induction medication only, 22% underwent intrauterine insemination and
      55% underwent in vitro fertilization. The median overall out-of-pocket expense
      was $5,338 (IQR 1,197-19,840). Couples using medication only had the lowest
      median out-of-pocket expenses at $912 while those using in vitro fertilization
      had the highest at $19,234. After multivariate adjustment the out-of-pocket
      expense was not significantly associated with successful pregnancy. On
      multivariate analysis couples treated with in vitro fertilization spent an
      average of $15,435 more than those treated with intrauterine insemination.
      Couples spent about $6,955 for each additional in vitro fertilization cycle.
      CONCLUSIONS: These data provide real-world estimates of out-of-pocket costs,
      which can be used to help couples plan for expenses that they may incur with
      treatment.

PMID- 24018236
TI  - Epigenetic inactivation of KLF4 is associated with urothelial cancer progression
      and early recurrence.
AB  - PURPOSE: KLF4 is a transcription factor with divergent functions in different
      malignancies. We analyzed KLF4 expression and DNA methylation, and their clinical
      relevance and biological function in urothelial cancer. MATERIALS AND METHODS:
      Immunohistochemistry and SequenomTM MassARRAY(r) were done to detect the
      expression and promoter methylation of KLF4 in urothelial cancer tissues. The
      association of the recurrence-free survival rate and decreased KLF4 or KLF4
      methylation status was analyzed by the Kaplan-Meier method, Cox regression
      analysis and ROC assay. Lentivirus based KLF4 over expression and dsRNA mediated
      knockdown were used to detect KLF4 functions in urothelial cancer in vitro and in
      vivo. RESULTS: KLF4 was down-regulated in urothelial cancer due to promoter
      hypermethylation. Each correlated with recurrence-free survival in patients with
      nonmuscle invasive bladder cancer after transurethral resection of bladder
      cancer, which potentiates them as valuable predictive biomarkers for early
      recurrence. Moreover, in and ex vivo experiments showed that KLF4 suppressed
      urothelial cancer cell growth, migration and invasion inhibited the epithelial-to
      mesenchymal transition. CONCLUSIONS: KLF4 may function as a tumor suppressor gene
      in urothelial cancer since down-regulation of KLF4 by promoter hypermethylation
      would promote cancer progression. In addition, decreased expression of KLF4 or
      its promoter hypermethylation may have predictive value for early recurrence in
      patients with nonmuscle invasive bladder cancer.

PMID- 24018237
TI  - The impact of repeat biopsies on infectious complications in men with prostate
      cancer on active surveillance.
AB  - PURPOSE: Prostate biopsy related infectious complications are associated with
      significant morbidity. The risk of infectious complications in patients with
      prostate cancer on active surveillance remains under studied. MATERIALS AND
      METHODS: A total of 591 consecutive men who underwent prostate biopsy were
      prospectively enrolled in a study evaluating prostate biopsy related
      complications between January 2011 and January 2012. Of these men 403 were
      previously diagnosed with prostate cancer and were included in this study. They
      underwent a 14-core transrectal ultrasound guided prostate biopsy as part of an
      active surveillance regimen. A nurse contacted all men within 14 days of biopsy,
      and information was collected on potential complications, antibiotics received
      and bacterial culture results. RESULTS: Fourteen patients (3.5%) had infectious
      complications including 13 requiring hospitalization. Five patients had positive
      urine cultures, and fluoroquinolone resistant isolates were identified in 4
      patients, including 2 with extended spectrum beta-lactamase producing isolates.
      We evaluated the impact of risk factors including diabetes, benign prostatic
      hyperplasia and antibiotic regimen. However, only the number of previous prostate
      biopsies was significantly associated with an increased risk of infectious
      complications (p = 0.041). For every previous biopsy the odds of an infection
      increased 1.3 times (OR 1.33, 95% CI 1.01-1.74). CONCLUSIONS: In men with
      prostate cancer on active surveillance the number of previous prostate biopsies
      is associated with a significant risk of infectious complications and every
      previous biopsy increases the risk of infectious complication. Fluoroquinolone
      resistant and extended spectrum beta-lactamase producing isolates represent the
      most commonly identified organisms. Men with prostate cancer on active
      surveillance should be informed of the risks associated with serial repeat
      prostate biopsies.

PMID- 24018238
TI  - Comprehensive assessment of the impact of cigarette smoking on survival of clear
      cell kidney cancer.
AB  - PURPOSE: The impact of modifiable environmental factors on kidney cancer specific
      outcomes is under studied. We evaluated the impact of smoking exposure on cancer
      specific survival in patients with clear cell renal cell carcinoma treated with
      surgery. MATERIALS AND METHODS: From a prospectively maintained database at a
      single center we collected the characteristics of 1,625 patients with clear cell
      renal cell carcinoma treated with surgery between 1995 through 2012. We
      determined the associations of smoking status with advanced disease, defined as
      AJCC (American Joint Committee on Cancer) stage greater than 2, and with cancer
      specific survival. RESULTS: The prevalence rate of current, former and never
      smoking at diagnosis was 16%, 30% and 54%, respectively. Of the patients 62%
      reported a smoking history of 20 pack-years or greater. Median followup in
      survivors was 4.5 years (IQR 2.2-7.9). On univariable analysis a smoking history
      of 20 pack-years or greater was associated with a significantly increased risk of
      advanced disease (OR 1.43, 95% CI 1.02-2.00). However, it did not achieve an
      independent association after adjusting for age and gender. Pathological stage
      and Fuhrman grade adversely affected cancer specific survival on multivariable
      competing risks analysis. Although the association between smoking and cancer
      specific survival did not achieve statistical significance on multivariable
      analysis, the direction of the central estimate (HR 1.5, 95% CI 0.89-2.52)
      suggested that smoking adversely impacts cancer specific survival. Current
      smokers faced a higher risk of death from another cause than never smokers (HR
      1.93, 95% CI 1.29-2.88). CONCLUSIONS: Smoking exposure substantially increases
      the risk of death from another cause and adversely impacts cancer specific
      survival in patients with clear cell renal cell carcinoma. Treatment plans to
      promote smoking cessation are recommended for these patients.

PMID- 24018239
TI  - Clinical outcomes for patients with metastatic renal cell carcinoma treated with
      alternative sunitinib schedules.
AB  - PURPOSE: We identified sunitinib alternative schedules that maintained dose
      intensity while decreasing adverse events in patients with metastatic renal cell
      cancer. We also determined the impact of alternative schedules on clinical
      outcomes. MATERIALS AND METHODS: We retrospectively reviewed the records of
      patients 18 years old or older with clear cell metastatic renal cell cancer who
      received first line sunitinib between January 26, 2006 and March 1, 2011 at our
      major comprehensive cancer center. A subset of patients was switched at the first
      intolerable adverse event from the traditional schedule of 28 days on and 14 days
      off to a schedule of 14 days on and 7 days off or other alternative schedules. A
      control group underwent standard dose reduction. We estimated progression-free
      and overall survival by the Kaplan-Meier method. Predictors of progression-free
      and overall survival were analyzed using Cox regression. RESULTS: A total of 187
      patients were included in analysis, of whom 87% were on the traditional schedule
      at baseline. During treatment 53% of patients continued on the traditional
      schedule and 47% began or were transitioned to alternative schedules. Baseline
      characteristics were similar. Adverse events prompting schedule modification
      included fatigue in 64% of cases, hand-foot syndrome in 38% and diarrhea in 32%.
      Median time to alternative schedules was 5.6 months. Median overall survival was
      17.7 months (95% CI 10.8-22.2) on the traditional schedule compared to 33.0
      months (95% CI 29.3-not estimable) on alternative schedules (p <0.0001). On
      multivariable analysis poor Eastern Cooperative Oncology Group (ECOG) performance
      status, increased lactate dehydrogenase, decreased albumin, unfavorable Heng
      criteria and the traditional schedule were associated with decreased overall
      survival (p <0.05). CONCLUSIONS: Sunitinib administered on alternative schedules
      may mitigate adverse events while achieving outcomes comparable to those of the
      traditional schedule in patients with metastatic renal cell cancer. Prospective
      investigations of alternate dosing schemas are warranted.

PMID- 24018240
TI  - Phase II study on the efficacy and safety of the EP1 receptor antagonist ONO-8539
      for nonneurogenic overactive bladder syndrome.
AB  - PURPOSE: We evaluated the efficacy, safety and tolerability of the EP1 receptor
      antagonist ONO-8539 in patients with overactive bladder syndrome. MATERIALS AND
      METHODS: This was a 12-week, randomized, double-blind, placebo controlled,
      parallel group, multicenter study with a 2-week single blind placebo run-in
      phase. The 435 patients were randomized to receive twice daily ONO-8539 (30, 100
      or 300 mg), placebo or once daily tolterodine (4 mg). RESULTS: At the end of the
      12-week treatment no statistically significant difference was found between ONO
      8539 and placebo in the change from baseline in the number of micturitions per 24
      hours. The primary end points for 30, 100 and 300 mg ONO-8539, and placebo were 
      1.02, -1.53, -1.31 and -1.40, respectively. There was no statistically
      significant difference between any ONO-8539 group and placebo in the change from
      baseline in the number of urgency or urinary urgency incontinence episodes per 24
      hours, or the mean volume voided per micturition, which were secondary end
      points. Statistically significant differences for tolterodine vs placebo were
      observed in the change from baseline in the number of micturitions (p = 0.045),
      urgency episodes (p = 0.04) and mean volume voided per micturition (p <0.001).
      The incidence of adverse events was 54.1% in the placebo group, 43.0% to 54.0% in
      the ONO-8539 groups and 46.6% in the tolterodine group. The intensity of adverse
      events was similar among the treatment groups. Similar to other treatments, the
      most frequently reported adverse events after ONO-8539 were nasopharyngitis and
      diarrhea. CONCLUSIONS: The results of this study, which to our knowledge
      represents the first evaluation of ONO-8539 in patients with overactive bladder,
      suggest a minimal role for EP1 receptor antagonism in the management of
      overactive bladder syndrome.

PMID- 24018241
TI  - Long-term device outcomes of artificial urinary sphincter reimplantation
      following prior explantation for erosion or infection.
AB  - PURPOSE: We evaluated clinical outcomes in patients treated with artificial
      urinary sphincter reimplantation after artificial urinary sphincter explantation
      for erosion or infection. MATERIALS AND METHODS: We identified 704 consecutive
      artificial urinary sphincter implantation procedures performed at our institution
      from 1998 to 2012, including 497 (71%) as primary implantation and 138 (20%) as
      revision surgery for device malfunction. A total of 69 patients (10%) had
      undergone at least 1 prior artificial urinary sphincter explantation secondary to
      urethral erosion and/or device infection, of whom 36 (52%) were treated with 2 to
      5 prior reimplantation procedures. Patient followup was performed through office
      examination, or written or telephone correspondence. RESULTS: Patients treated
      with artificial urinary sphincter reimplantation had a median age of 78 years
      (IQR 72, 80) and a median followup of 34 months (IQR 5, 61). Artificial urinary
      sphincter reimplantation was done a median of 9 months (IQR 6, 13) after
      explantation. Patients treated with reimplantation after erosion or infection
      were more likely to require repeat explantation than those with primary
      implantation (13 of 69 or 19% vs 32 of 497 or 6.4%, p = 0.002). However, when
      evaluating repeat procedures, the 5-year device survival rate after
      reimplantation due to erosion or infection vs primary implantation was 68% vs 76%
      (p = 0.38). CONCLUSIONS: Our findings suggest that artificial urinary sphincter
      reimplantation after explantation for urethral erosion and/or device infection is
      associated with an increased rate of recurrent erosion/infection requiring repeat
      explantation. However, in appropriately selected and counseled patients
      clinically acceptable long-term device use can be achieved.

PMID- 24018242
TI  - Prevalence of 24-hour urine collection in high risk stone formers.
AB  - PURPOSE: Secondary prevention has an important role in urinary stone disease. The
      core of secondary prevention is the identification of modifiable risk factors by
      a 24-hour urine collection, which then directs selective medical therapy. While
      this decreases the recurrence rate, little is known about the frequency with
      which 24-hour urine collections are obtained. MATERIALS AND METHODS: Using
      medical claims from 2002 to 2006 we identified adults with incident urinary stone
      episodes. With appropriate diagnosis codes we determined those at high risk for
      recurrence. Of these patients we determined the proportion in whom a 24-hour
      urine collection was done within 6 months of diagnosis. Finally, we fitted
      regression models to measure associations between patient and provider level
      factors, and obtaining a 24-hour urine collection. RESULTS: We identified 28,836
      patients at high risk for recurrence. The prevalence of 24-hour urine testing
      increased from 7.0% in 2003 to 7.9% in 2006 (p = 0.011), although the overall
      prevalence was exceedingly low at 7.4%. Multivariable regression revealed that
      region of residence and level of comorbid illness were independently associated
      with 24-hour urine collection, as was the type of physician who performed the
      followup. For instance, the odds of metabolic evaluation were 2.9 times higher
      when a patient was seen by a nephrologist (OR 2.92, 95% CI 2.32-3.67), and more
      than threefold higher when seen by a urologist (OR 3.87, 95% CI 3.48-4.30).
      CONCLUSIONS: Obtaining 24-hour urine collections in stone formers at high risk is
      uncommon, raising a quality of care concern.

PMID- 24018243
TI  - Improving referral activity on primary-secondary care interface using an
      electronic decision support system.
AB  - OBJECTIVE: Our main aim was to evaluate the ability of electronic feedback and of
      an electronic referral decision support system (ERSS) to enhance agreement
      between primary care physicians (PCPs) and specialists in priority assignment in
      clinics. METHOD: 62 PCPs used a ranking system of waiting times based on
      different categories of clinical priority called 'Homogeneous Waiting Groups'
      (HWGs), which was also used by specialists to assign a priority category for each
      patient. From the year 2001, all PCPs had to use a paper-based manual (group 1);
      instead from 2008, specialists began to use a computer-based tool, whereby the
      priority category reassigned to each patient by specialists promptly appeared on
      PCPs' computers (group 2). During the course of 2010, the manual was incorporated
      in ERSS and was used by a subgroup of PCPs (group 3). Agreement between PCPs and
      specialists' priority assignments was evaluated by the kappa statistic. RESULTS:
      In group 1, the kappa statistic was 0.564 (95% CI=0.526-0.602); in group 2, the
      kappa statistic was 0.668 (95% CI=0.619-0.716); whereas in group 3 (that used
      ERSS) a very high kappa statistic emerged of 0.883 (95% CI=0.854-0.912). There
      was a significant difference in the proportion of agreement among the three
      groups (chi(2)=182.5, 2df, p<.0001). A significant difference in statistics was
      also observed in the proportion of priority levels used by PCPs over the years.
      CONCLUSIONS: Our results emphasize the positive effect of feedback and ERSS for
      improving referral activity and agreement between PCPs and specialists.

PMID- 24018244
TI  - Mucosal healing in inflammatory bowel disease: treatment efficacy and predictive
      factors.
AB  - In recent years mucosal healing has emerged as an important therapeutic goal for
      patients with inflammatory bowel disease. Growing evidence suggests that
      achieving mucosal healing can improve patient outcomes and, potentially, alter
      the course of the disease. Drugs currently used in the management of inflammatory
      bowel disease are potentially able of inducing and maintaining mucosal healing,
      but the effect size is difficult to assess because of different definitions of
      mucosal healing, differences in study designs, and timing of endoscopic
      evaluation. Mucosal healing has been studied extensively in the biologic era.
      Data available from different sources, such as controlled trials and
      observational studies, show that anti-TNFalpha therapies can induce rapid and
      sustained mucosal healing in a variable percentage of patients with Crohn's
      disease and ulcerative colits. No controlled study has been designed to identify
      possible predictors of mucosal healing. Some clinical characteristics such as
      extensive disease, young age at diagnosis, and smoking status may be predictive
      of a more aggressive clinical course and, presumably, of a reduced clinical and
      endoscopic response to therapy. Changes and normalization of C-reactive protein
      and faecal calprotectin may be useful tools to predict outcomes, guide the timing
      for endoscopic evaluation and, possibly, reduce the need of endoscopic evaluation
      in assessing mucosal healing. 

PMID- 24018246
TI  - [Use of intravenous immunoglobulins in a patient with systemic capillary leak
      syndrome].

PMID- 24018247
TI  - [Protocol of treatment of vitamin D deficiency].

PMID- 24018248
TI  - [The FRAX((r)) tool in the prevention of fractures associated with androgenic
      deprivation therapy for prostate cancer].

PMID- 24018249
TI  - [Systematic approach to the diagnosis of hyperferritinemia].

PMID- 24018250
TI  - [Extrinsic allergic alveolitis in cheese scrubbers].

PMID- 24018251
TI  - [Genetics of sudden unexplained death].
AB  - Sudden unexplained death is defined by death without a conclusive diagnosis after
      autopsy and it is responsible for a large percentage of sudden deaths. The
      progressive interaction between genetics and forensics in post-mortem studies has
      identified inheritable alterations responsible for pathologies associated with
      arrhythmic sudden death. The genetic diagnosis of the deceased enables the
      undertaking of preventive measures in family members, many of them asymptomatic
      but at risk. The implications of this multidisciplinary translational medical
      approach are complex, requiring the dedication of a specialized team. 

PMID- 24018252
TI  - [Hepatic hydrothorax: report of a series of 77 patients].
AB  - BACKGROUND AND OBJECTIVE: To describe the clinical characteristics, the most
      effective treatment and survival of cirrhotic patients with hepatic hydrothorax
      (HH). PATIENTS AND METHOD: Descriptive and retrospective analysis of a cohort of
      consecutive patients with HH undergoing a diagnostic thoracentesis. The
      biochemical and radiological features of the pleural effusion, its control with
      different therapies and the factors affecting survival were evaluated, among
      other parameters. RESULTS: Seventy-seven patients with HH were included, of whom
      14% did not have ascites. HH was right-sided in 77% of the cases, and occupied
      half or more of the hemithorax in 68%. Pleural fluids were transudative in 81% of
      the cases. Diuretic-resistant HH (27%) could be managed with liver
      transplantation, transjugular intrahepatic portosystemic shunt (TIPS) or
      indwelling pleural catheters. However, pleurodesis failed in most patients.
      Median survival was 9.1 months, and it was only favorably affected by liver
      transplantation. CONCLUSIONS: HH has a limited survival, only influenced by liver
      transplantation. In diuretic-resistant cases, TIPS or pleural indwelling
      catheters should be considered as a management option.

PMID- 24018253
TI  - [Educational intervention for the prevention of osteoporosis in a rural primary
      healthcare service].
AB  - BACKGROUND AND OBJECTIVE: The aim of this study is to determine whether an
      educational intervention in perimenopausal women in rural environments achieves
      significant changes in risk behaviors related to osteoporosis. MATERIAL AND
      METHODS: Randomized clinical trials of parallel groups: 216 women (45-54 years
      old) of a rural Primary Healthcare service. Pre- and post- intervention were
      covered: body mass index (BMI), densitometry and blood test (calcium [Ca],
      parathormone [PTH]). Intervention group (n1=110): 2 interactive workshops on the
      prevention of osteoporosis. Control group (n2=106): information by post. RESULTS:
      After the educational intervention, the intervention group maintained its BMI,
      increased its bone mineral density (BMD) (P<.001) and decreased the Ca (P <=.048)
      and PTH (P<.001) levels. The control group increased its BMI (P<.001) and its BMD
      (P <=.048), maintained its Ca levels and decreased the PTH values (P=.01).
      CONCLUSIONS: The improvement in the objective parameters related to osteoporosis
      indicates the importance of health education as a preventive measure in this
      group of women. It would be interesting to analyze the repercussions of this
      improvement on a long-term basis in terms of reducing the incidence of
      osteoporosis and fractures.

PMID- 24018254
TI  - [Morphea type plaques induced by paclitaxel].

PMID- 24018255
TI  - Direct and indirect effects of social support on youth physical activity
      behavior.
AB  - Social support (SS) from parents and peers are key reinforcing factors in the
      Youth Physical Activity Promotion (YPAP) model. This study aims to identify the
      relative contribution of parental and peer SS on youth participation in moderate
      to vigorous physical activity (MVPA). Participants included 203 high school
      students (n = 125 girls; mean age 14.99 +/- 1.55 years). MVPA was assessed by
      accelerometry. SS influences were evaluated using a well-established scale.
      Structural equation modeling measured (AMOS, Version 19) the relative fit of the
      YPAP models using both parental and peer SS. Parental SS had significant
      associations with both predisposing factors, enjoyment (beta = .62, p < .01), and
      self-efficacy (beta= .32, p < .01), as well a direct effect on MVPA (beta = .30,
      p < .01). Peer SS had direct effect on MVPA (beta = .33, p < .05), also
      significantly influenced levels of enjoyment (beta = .47, p < .01) and self
      efficacy (beta = .67, p < .01). In both models self-efficacy mediated the
      influence on MVPA. The direct effects for parents and peers were similar. This
      demonstrates that both parental and peer social support exert a strong influence
      on adolescent MVPA. 

PMID- 24018256
TI  - Clinical experience using polyetheretherketone (PEEK) intervertebral structural
      cage for anterior cervical corpectomy and fusion.
AB  - Anterior cervical corpectomy and fusion (ACCF) is commonly performed for various
      pathologies involving the cervical spine. Although polyetheretherketone (PEEK)
      cages have been widely used following anterior cervical discectomy and fusion
      (ACDF), clinical literature demonstrating its efficacy following ACCF is sparse.
      A retrospective review of patients enrolled in a prospective database who
      underwent single/multi-level ACCF was performed. Fifty-nine patients were
      identified who underwent corpectomy reconstruction with PEEK cages for
      symptomatic degenerative, neoplastic, infectious, or traumatic pathologies of the
      cervical spine. Thirty-five patients having at least 6 months follow-up (FU) were
      included in the final analysis. The mean age of patients was 51 years (range, 18
      81 years) with FU ranging from 6 to 33 months (mean, 6.6 months). None of the
      patients had dysphagia at last FU. There was no implant failure with fusion
      occurring in all patients. While 57% of patients (20/35) remained stable with no
      progression of myelopathy, 43% (15/35) improved one (11 patients) or two (four
      patients) Nurick grades after surgery. The use of PEEK cages packed with
      autograft or allograft is safe and effective following anterior cervical
      corpectomy, demonstrating high fusion rates and good clinical results. This
      synthetic material obviates the morbidity associated with autograft harvest and
      possible infectious risks of allograft. The wide array of cage dimensions
      facilitates ease of use in patients of all sizes and appears safe for use in the
      typical pathologic conditions encountered in the cervical spine.

PMID- 24018257
TI  - Glioblastoma arising in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome.
AB  - Mayer-Rokitansky-Kuster-Hauser syndrome is a rare developmental disorder marked
      by the congenital absence of the uterus and vagina. The syndrome has been
      associated with tumors of the female reproductive system, but rarely in other
      organ systems and to our knowledge, never in the brain. We report a glioblastoma
      in a 34-year-old patient with Mayer-Rokitansky-Kuster-Hauser syndrome.

PMID- 24018258
TI  - Radiation-induced primary cerebral atypical teratoid/rhabdoid tumour in an adult.
AB  - Atypical teratoid/rhabdoid tumours (ATRT) of the central nervous system are
      uncommon embryonal carcinomas that predominantly affect infants and young
      children, and less commonly adults. We report a 58 year old woman who presented
      with ATRT involving the right parietal lobe which was treated with surgery and
      adjuvant radiotherapy. Her history was significant for soft tissue sarcoma of the
      right ear treated with surgery and adjuvant radiotherapy at age 3, thus raising
      the possibility of radiation-induced aetiology.

PMID- 24018259
TI  - Secondary prevention of venous thromboembolism.

PMID- 24018260
TI  - Rapid viral expansion and short drug half-life explain the incomplete
      effectiveness of current herpes simplex virus 2-directed antiviral agents.
AB  - The nucleoside analogues acyclovir (ACV) and famciclovir (FCV) reduce the
      frequency and severity of herpes simplex virus 2 (HSV-2) genital shedding, yet
      despite their high potency in vitro and a lack of induced drug resistance,
      frequent episodes of breakthrough mucosal shedding occur. We tested a published
      stochastic, spatial mathematical model of HSV-2 replication and spread, in
      concert with pharmacokinetic and pharmacodynamic equations, against virologic
      data from clinical trials of twice-daily acyclovir and famciclovir suppression.
      The model reproduced the key features of clinical trial data, including genital
      shedding episode rate, expansion and decay dynamics, and heterogeneous peak viral
      production and duration. In simulations, these agents shortened episode duration
      by limiting the extent of viral production by 1 to 2 log units and limiting the
      formation of secondary ulcers by ~50%. However, drug concentrations were
      noninhibitory during 42% of the dosing cycle. Even if drug concentrations were
      high at episode initiation, prolonged episodes often ensued due to drug decay
      over ensuing hours and subsequent rebound of rapidly replicating HSV-2. The local
      CD8(+) T-cell density was more predictive of episode viral production (R(2) =
      0.42) and duration (R(2) = 0.21) than the drug concentration at episode onset
      (R(2) = 0.14 and 0.05, respectively), though the model projected that an agent
      with an equivalent potency but a two times longer half-life would decrease
      shedding by 80% compared to that of standard twice-daily regimens. Therefore,
      long half-life is a key characteristic of any agent that might fully suppress HSV
      2 reactivations. 

PMID- 24018261
TI  - Comprehensive identification of mutations responsible for heterogeneous
      vancomycin-intermediate Staphylococcus aureus (hVISA)-to-VISA conversion in
      laboratory-generated VISA strains derived from hVISA clinical strain Mu3.
AB  - Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) spontaneously
      produces VISA cells within its cell population at a frequency of 10(-6) or
      greater. We established a total of 45 VISA mutant strains independently obtained
      from hVISA Mu3 and its related strains by one-step vancomycin selection. We then
      performed high-throughput whole-genome sequencing of the 45 strains and their
      parent strains to identify the genes involved in the hVISA-to-VISA phenotypic
      conversion. A comparative genome study showed that all the VISA strains tested
      carried a unique set of mutations. All of the 45 VISA strains carried 1 to 4
      mutations possibly affecting the expression of a total of 48 genes. Among them,
      32 VISA strains carried only one gene affected by a single mutation. As many as
      20 genes in more than eight functional categories were affected in the 32 VISA
      strains, which explained the extremely high rates of the hVISA-to-VISA phenotypic
      conversion. Five genes, rpoB, rpoC, walK, pbp4, and pp2c, were previously
      reported as being involved in vancomycin resistance. Fifteen remaining genes were
      newly identified as associated with vancomycin resistance in this study. The gene
      most frequently affected (6 out of 32 strains) was cmk, which encodes cytidylate
      kinase, followed closely by rpoB (5 out of 32), encoding the beta subunit of RNA
      polymerase. A mutation prevalence study also revealed a sizable number of cmk
      mutants among clinical VISA strains (7 out of 38 [18%]). Reduced cytidylate
      kinase activity in cmk mutant strains is proposed to contribute to the hVISA-to
      VISA phenotype conversion by thickening the cell wall and reducing the cell
      growth rate. 

PMID- 24018262
TI  - Ciprofloxacin treatment failure in a murine model of pyelonephritis due to an
      AAC(6')-Ib-cr-producing Escherichia coli strain susceptible to ciprofloxacin in
      vitro.
AB  - AAC(6')-Ib-cr is a plasmid-mediated quinolone resistance mechanism described
      worldwide for Escherichia coli. Since it confers in vitro only a low level of
      resistance to ciprofloxacin, we evaluated its impact on the in vivo activity of
      ciprofloxacin. Isogenic strains were obtained by transferring plasmid p449,
      harboring aac(6')-Ib-cr, into the quinolone-susceptible strain E. coli CFT073-RR
      and its D87G gyrA mutant. MICs were 0.015, 0.06, 0.25, and 0.5 MUg/ml against E.
      coli strains CFT073-RR, CFT073-RR/p449, CFT073-RR GyrA(r), and CFT073-RR
      GyrA(r)/p449, respectively. Bactericidal activity was reduced at 1* the MIC for
      the three resistant derivatives, while at a fixed concentration of 0.5 MUg/ml,
      99.9% killing was observed for all strains except E. coli CFT073-RR GyrA(r)/p449.
      In the murine model of pyelonephritis, an optimal regimen of ciprofloxacin (10
      mg/kg of body weight twice a day [b.i.d.]) significantly decreased the bacterial
      count in the kidneys of mice infected with E. coli CFT073 (1.6 versus 4.3 log10
      CFU/g of kidney compared to untreated controls; P = 0.0001), while no significant
      decrease was observed for E. coli CFT073-RR/p449 (2.7 versus 3.1 log10 CFU/g; P =
      0.84), E. coli CFT073-RR GyrA(r) (4.2 versus 4.1 log10 CFU/g; P = 0.35), or E.
      coli CFT073-RR GyrA(r)/p449 (2.9 versus 3.6 log10 CFU/g; P = 0.47). While
      pharmacokinetic and pharmacodynamic (PK/PD) parameters accounted for
      ciprofloxacin failure against gyrA-containing mutants, this was not the case for
      the aac(6')-Ib-cr-containing strains, suggesting an in situ hydrolysis of
      ciprofloxacin in the latter case. 

PMID- 24018263
TI  - Interlaboratory variability of Caspofungin MICs for Candida spp. Using CLSI and
      EUCAST methods: should the clinical laboratory be testing this agent?
AB  - Although Clinical and Laboratory Standards Institute (CLSI) clinical breakpoints
      (CBPs) are available for interpreting echinocandin MICs for Candida spp.,
      epidemiologic cutoff values (ECVs) based on collective MIC data from multiple
      laboratories have not been defined. While collating CLSI caspofungin MICs for 145
      to 11,550 Candida isolates from 17 laboratories (Brazil, Canada, Europe, Mexico,
      Peru, and the United States), we observed an extraordinary amount of modal
      variability (wide ranges) among laboratories as well as truncated and bimodal MIC
      distributions. The species-specific modes across different laboratories ranged
      from 0.016 to 0.5 MUg/ml for C. albicans and C. tropicalis, 0.031 to 0.5 MUg/ml
      for C. glabrata, and 0.063 to 1 MUg/ml for C. krusei. Variability was also
      similar among MIC distributions for C. dubliniensis and C. lusitaniae. The
      exceptions were C. parapsilosis and C. guilliermondii MIC distributions, where
      most modes were within one 2-fold dilution of each other. These findings were
      consistent with available data from the European Committee on Antimicrobial
      Susceptibility Testing (EUCAST) (403 to 2,556 MICs) for C. albicans, C. glabrata,
      C. krusei, and C. tropicalis. Although many factors (caspofungin powder source,
      stock solution solvent, powder storage time length and temperature, and MIC
      determination testing parameters) were examined as a potential cause of such
      unprecedented variability, a single specific cause was not identified. Therefore,
      it seems highly likely that the use of the CLSI species-specific caspofungin CBPs
      could lead to reporting an excessive number of wild-type (WT) isolates (e.g., C.
      glabrata and C. krusei) as either non-WT or resistant isolates. Until this
      problem is resolved, routine testing or reporting of CLSI caspofungin MICs for
      Candida is not recommended; micafungin or anidulafungin data could be used
      instead. 

PMID- 24018264
TI  - Pharmacodynamic target attainment for various ceftazidime dosing schemes in high
      flux hemodialysis.
AB  - Ceftazidime is a broad-spectrum cephalosporin with high-level activity against a
      variety of Gram-negative pathogens, including Pseudomonas aeruginosa. Improved
      outcomes are associated with cumulative percentages of a 24-h period that the
      drug concentration exceeds the MIC under steady-state pharmacokinetic conditions
      (%TMIC) of >45 to 70% of the dosing interval. Optimal dosing to achieve a 90%
      probability of target attainment (PTA) in patients receiving high-flux
      hemodialysis (HFHD) is unknown. We used existing data from six anephric adults
      receiving hemodialysis to construct a population model with the Pmetrics package
      for R. From the final model's joint probability density, we simulated the PTA for
      various ceftazidime dosing regimens, HFHD schedules, and organism MICs. For HFHD
      every 48 h and 1 g of ceftazidime given posthemodialysis, the PTA exceeds 90% for
      all isolates with MICs of <=8 MUg/ml, assuming a goal of 70%TMIC. For 72-h
      dialysis intervals, postdialysis dosing of 1 g is adequate for achievement of the
      70%TMIC goal only for organisms with MICs of <=4 MUg/ml, while 2 g is adequate
      for organisms with MICs of <=8 MUg/ml. A dose of 500 mg once daily, regardless of
      HFHD schedule, has a 90% PTA for organisms with MICs of <=16 MUg/ml, while 1 g
      once daily may achieve 100% PTA even for resistant organisms with a MIC of 32
      MUg/ml. Therefore, to ensure maximal ceftazidime activity, once-daily dosing of
      500 mg to 1 g ceftazidime in patients receiving HFHD may be preferable for
      critically ill patients when MIC data are unavailable and for more resistant
      organisms with ceftazidime MICs of 16 to 32 MUg/ml. 

PMID- 24018265
TI  - Environmental Shewanella xiamenensis strains that carry blaOXA-48 or blaOXA-204
      genes: additional proof for blaOXA-48-like gene origin.

PMID- 24018266
TI  - Mild cognitive impairment and anti-Alzheimer disease medications: A cross
      sectional study of the French National Alzheimer Databank (BNA).
AB  - Unlike Alzheimer's disease (AD), there are no drugs approved for the treatment of
      mild cognitive impairment (MCI). The objective of this study was to evaluate real
      world prescriptions of anti-AD medications in patients with MCI in France and to
      determine characteristics associated with treatment. A cross sectional study of
      the French National Alzheimer Databank (BNA) was conducted. Patients diagnosed
      with MCI by physicians of the BNA network in 2010 and 2011 were included in this
      study. We included 16,236 patients with a diagnosis of MCI in the study. Mean age
      was 76.4 years old and females were 59.5%. Nine hundred eighty five patients
      (6.1%) were taking an anti-AD medication. Results of a multivariate analysis show
      that use was associated with older age, lower MMSE score, amnestic MCI subtype,
      living at home, and higher education. Treatment with antidepressant drugs was
      also associated with anti-AD medication use (odd ratio: 1.68; 95% confidence
      interval: 1.44 to 1.96). "Off label" prescription of anti-AD drugs is low in
      France and seems to be limited to a population at risk of conversion to AD.
      Similar analysis will be required to monitor this practice in the future.

PMID- 24018267
TI  - Secretory leukocyte protease inhibitor protein regulates the penetrance of
      frontotemporal lobar degeneration in progranulin mutation carriers.
AB  - The discovery that mutations in the gene encoding for progranulin (GRN) cause
      frontotemporal lobar degeneration (FTLD) and other neurodegenerative diseases
      leading to dementia has brought renewed interest in progranulin and its functions
      in the central nervous system. Full length progranulin is preserved from cleavage
      by secretory leukocyte protease inhibitor (SLPI), one of the smallest serine
      protease inhibitor circulating in plasma. Herein, we investigated the
      relationship between circulating SLPI and progranulin in affected and unaffected
      subjects belonging to 26 Italian pedigrees carrying GRN null mutations. In GRN
      null mutation carriers, we demonstrated: i) an increase of circulating SLPI
      levels in affected subjects; ii) an age-related upregulation of the serine
      protease inhibitor in response to lifetime progranulin shortage; and iii) a delay
      in the age of onset in subjects with the highest SLPI protein levels. The study
      of SLPI and its relation to progranulin suggests the existence of unexpected
      molecular players in progranulin-associated neurodegeneration.

PMID- 24018268
TI  - Social cognition and interaction training for patients with stable schizophrenia
      in Chinese community settings.
AB  - Accumulated evidence suggests that Social Cognition and Interaction Training
      (SCIT) is associated with improved performance in social cognition and social
      skills in patients diagnosed with psychotic disorders. The current study examined
      the clinical utility of SCIT in patients with schizophrenia in Chinese community
      settings. Adults with stable schizophrenia were recruited from local community
      health institutions, and were randomly assigned to SCIT group (n = 22) or a
      waiting-list control group (n = 17). The SCIT group received the SCIT
      intervention plus treatment-as-usual, whereas the waiting-list group received
      only treatment-as-usual during the period of the study. All patients were
      administered the Chinese versions of the Personal and Social Performance Scale
      (PSP), Face Emotion Identification Task (FEIT), Eyes task, and Attributional
      Style Questionnaire (ASQ) at baseline of the SCIT treatment period and at follow
      up, 6 months after completion of the 20-week treatment period. Patients in SCIT
      group showed a significant improvement in the domains of emotion perception,
      theory of mind, attributional style, and social functioning compared to those in
      waiting-list group. Findings indicate that SCIT is a feasible and promising
      method for improving social cognition and social functioning among Chinese
      outpatients with stable schizophrenia.

PMID- 24018269
TI  - Are immature psychological defense mechanisms recently associated with junk food,
      alcohol, and television also associated with age?

PMID- 24018271
TI  - Rapid deletion and inactivation of CTLs upon recognition of a number of target
      cells over a critical threshold.
AB  - Initiation of CTL responses against foreign pathogens also primes anti-self CTLs.
      Mechanisms of CTL inactivation inhibit anti-self CTLs to prevent tissue damage.
      These mechanisms are exploited by pathogens and tumors to evade the immune
      response, and present a major hurdle to adoptive CTL therapies. It is unclear
      whether CTL inactivation is Ag specific and, if so, which APCs are involved.
      Potential candidates include the target cells themselves, dendritic cells,
      myeloid-derived suppressor cells, and macrophages. In this study, we show that
      lymphoma-specific CTLs are rapidly deleted in an Ag-specific manner after
      adoptive transfer into lymphoma-bearing mice, and the surviving CTLs are
      functionally impaired. The only APCs responsible were the target cells directly
      presenting Ag, notwithstanding the presence of myeloid-derived suppressor cells,
      and CD8(+) dendritic cells cross-presenting tumor Ag. The capacity to inactivate
      CTLs critically depended on the number of tumor/target cells; small numbers of
      targets were readily killed, but a large number caused quick deletion and
      functional inactivation of the CTLs. Application of mild, noninflammatory, and
      nonlymphoablative chemotherapy to specifically reduce tumor burden before CTL
      injection prevented CTL deletion and inactivation and allowed eradication of
      tumor. Our results advocate the use of adoptive CTL therapy soon after mild
      chemotherapy. They also suggest a simple mechanism for Ag-specific impairment of
      anti-self CTLs in the face of an active anti-foreign CTL response. 

PMID- 24018270
TI  - HLA-F and MHC class I open conformers are ligands for NK cell Ig-like receptors.
AB  - Killer Ig-like receptors (KIRs) are innate immune receptors expressed by NK and T
      cells classically associated with the detection of missing self through loss of
      their respective MHC ligand. Some KIR specificities for allelic classical class I
      MHC (MHC-I) have been described, whereas other KIR receptor-ligand relationships,
      including those associated with nonclassical MHC-I, have yet to be clearly
      defined. We report in this article that KIR3DL2 and KIR2DS4 and the nonclassical
      Ag HLA-F, expressed as a free form devoid of peptide, physically and functionally
      interact. These interactions extend to include classical MHC-I open conformers as
      ligands, defining new relationships between KIR receptors and MHC-I. The data
      collectively suggest a broader, previously unrecognized interaction between MHC-I
      open conformers--including prototypical HLA-F--and KIR receptors, acting in an
      immunoregulatory capacity centered on the inflammatory response.

PMID- 24018272
TI  - Induction of cyclooxygenase-2 signaling by Stomatococcus mucilaginosus highlights
      the pathogenic potential of an oral commensal.
AB  - Stomatococcus mucilaginosus is an oral commensal that has been occasionally
      reported to cause severe infections in immunocompromised patients. There is no
      information about the pathogenic role of S. mucilaginosus in airway infections.
      In a cohort of 182 subjects with bronchiectasis, we found that 9% were colonized
      with S. mucilaginosus in their lower airways by culture growth from
      bronchoalveolar lavage. To address the pathogenic potential of S.mucilaginosus,
      we developed a murine model of S. mucilaginosus lung infection. Intratracheal
      injection of S. mucilaginosus in C57BL/6 mice resulted in a neutrophilic influx
      with production of proinflammatory cytokines, chemokines, and lipid mediators,
      mainly PGE2 with induction of cyclooxygenase-2 (COX-2) in the lungs. Presence of
      TLR2 was necessary for induction of COX-2 and production of PGE2 by S.
      mucilaginosus. TLR2-deficient mice showed an enhanced clearance of S.
      mucilaginosus compared with wild-type mice. Administration of PGE2 to TLR2(-/-)
      mice resulted in impaired clearance of S. mucilaginosus, suggesting a key role
      for COX-2-induced PGE2 production in immune response to S. mucilaginosus.
      Mechanistically, induction of COX-2 in macrophages was dependent on the p38
      ERK/MAPK signaling pathway. Furthermore, mice treated with S. mucilaginosus and
      Pseudomonas aeruginosa showed an increased mortality compared with mice treated
      with PA103 or S. mucilaginosus alone. Inhibition of COX-2 significantly improved
      survival in mice infected with PA103 and S. mucilaginosus. These data provide
      novel insights into the bacteriology and personalized microbiome in patients with
      bronchiectasis and suggest a pathogenic role for S. mucilaginosus in patients
      with bronchiectasis.

PMID- 24018273
TI  - Comparison of vaccine-induced effector CD8 T cell responses directed against self
      and non-self-tumor antigens: implications for cancer immunotherapy.
AB  - It is generally accepted that CD8 T cells play a major role in tumor control, yet
      vaccination aimed at eliciting potent CD8 T cell responses are rarely efficient
      in clinical trials. To try and understand why this is so, we have generated
      potent adenoviral vectors encoding the endogenous tumor Ags (TA) tyrosinase
      related protein-2 (TRP-2) and glycoprotein 100 (GP100) tethered to the invariant
      chain (Ii). Using these vectors, we sought to characterize the self-TA-specific
      CD8 T cell response and compare it to that induced against non-self-Ags expressed
      from a similar vector platform. Prophylactic vaccination with adenoviral vectors
      expressing either TRP-2 (Ad-Ii-TRP-2) or GP100 (Ad-Ii-GP100) had little or no
      effect on the growth of s.c. B16 melanomas, and only Ad-Ii-TRP-2 was able to
      induce a marginal reduction of B16 lung metastasis. In contrast, vaccination with
      a similar vector construct expressing a foreign (viral) TA induced efficient
      tumor control. Analyzing the self-TA-specific CD8 T cells, we observed that these
      could be activated to produce IFN-gamma and TNF-alpha. In addition, surface
      expression of phenotypic markers and inhibitory receptors, as well as in vivo
      cytotoxicity and degranulation capacity matched that of non-self-Ag-specific CD8
      T cells. However, the CD8 T cells specific for self-TAs had a lower functional
      avidity, and this impacted on their in vivo performance. On the basis of these
      results and a low expression of the targeted TA epitopes on the tumor cells, we
      suggest that low avidity of the self-TA-specific CD8 T cells may represent a
      major obstacle for efficient immunotherapy of cancer. 

PMID- 24018274
TI  - Impact of grass/forage feeding versus grain finishing on beef nutrients and
      sensory quality: the U.S. experience.
AB  - Studies of forage and/or grass feeding of cattle versus grain finishing have been
      conducted in varying regions throughout the world but generalization of these
      results to beef from U.S. cattle may not be appropriate. In particular, available
      grass/forage variety and form as well as cattle breed have a significant impact
      on the nutritional profile of beef. The current review summarizes the nutritional
      characteristics of beef as reported from the limited number of studies comparing
      U.S. grass/forage-fed versus grain-finished cattle and estimates the intake of
      key nutrients that might be expected from consumption of U.S. beef from either
      feeding system. In addition, many studies report changes in fatty acids solely as
      a percentage of total fatty acids. Since grass/forage feeding typically results
      in a leaner product; the current review compares the fatty acid profile of beef
      from grass/forage feeding to that of grain-finished cattle on a mg/100 g of meat
      basis.

PMID- 24018275
TI  - Stability of lamb loin stored under refrigeration and packed in different
      modified atmosphere packaging systems.
AB  - The aim of the present study was to evaluate the effect of different modified
      atmosphere packaging (MAP) systems (vacuum, 75% O2+25% CO2 and 100% CO2) on the
      stability of lamb loins stored at 1+/-1 degrees C for 28 days. Microbiological
      (counts of aerobic and anaerobic psychrotrophic microorganisms, coliform at 45
      degrees C, coagulase-positive staphylococci and lactic acid bacteria and presence
      of Salmonella), physical and chemical (thiobarbituric acid reactive substances
      [TBARS], objective color, pH, water loss from cooking [WLC] and shear force),
      sensory (acceptance testing using a 9-point hedonic scale) and gas composition
      analyses were performed. Lamb meat remained stable with respect to the majority
      of the evaluated physical and chemical indexes and within the standards
      established by Brazilian legislation for pathogenic microorganisms throughout the
      storage period in all three packaging systems. However, with respect to
      psychrotrophic microorganisms, 100% CO2 packaging system provided increased
      stability despite presenting lower appearance preference.

PMID- 24018276
TI  - Fatty acid profile and cholesterol content of beef at retail of Piemontese,
      Limousin and Friesian breeds.
AB  - Samples of longissimus thoracis muscle of young bulls belonging to Piemontese
      (n=10), Limousin (n=11) and Friesian (n=10) breeds were analysed in order to
      study the chemical composition, fatty acids and cholesterol content of beef
      purchased at retail. The breeds and their differences in intramuscular fat
      content strongly influenced the fatty acids profile. The Piemontese animals
      displayed the lowest intramuscular fat and SFA content, while Friesian animals
      showed the highest intramuscular fat, SFA and MUFA content. In general, Limousin
      animals had intermediate characteristics. A higher PUFA proportion on total fatty
      acids was observed in Piemontese breed, but the PUFA absolute content (mg/100 g
      meat) did not differ among breeds. All the three breeds displayed a high content
      of n-6 fatty acids family and, consequently, a very unbalanced n-6/n-3 ratio. No
      differences were found for cholesterol content.

PMID- 24018277
TI  - Meat quality of buffalo young bulls fed faba bean as protein source.
AB  - Sixteen Italian Mediterranean Buffalo young bulls were divided into two groups
      fed isoprotein and isoenergy diets and only differing for protein source of
      concentrate: faba bean (FB) vs soybean (SB). Animals were slaughtered at 350 kg
      BW. Meat from FB group showed significantly lower fat, protein, cholesterol and
      saturated fatty acids than SB group. Significant differences were also found
      between the three muscles analysed [Longissimus thoracis (LT), Semitendinosus
      (ST) and Iliopsoas plus Psoas minor (IP)]. ST showed the most favourable fatty
      acids profile: lower SFA, higher PUFA, MUFA, omega-3, omega-6, CLA and,
      consequently, lower values for both atherogenic and thrombogenic indexes. Results
      showed that faba bean can be used as a protein source alternative to soybean in
      the diet of young buffalo bulls for the production of high quality meat.

PMID- 24018278
TI  - Fatty acid profile, color and lipid oxidation of meat from young bulls fed ground
      soybean or rumen protected fat with or without monensin.
AB  - The objective of the present study was to evaluate the meat quality and fatty
      acid (FA) profile of the muscle and subcutaneous fat of young bulls fed ground
      soybean grain (SB) or rumen protected fat (RPF) with (230 mg head(-1) day(-1)) or
      without monensin. Forty animals with an initial weight of 359 kg were allotted in
      a 2*2 factorial arrangement of treatments. The use of monensin increased the
      arachidonic and alpha-linolenic acids in the longissimus dorsi (LD) muscle and
      subcutaneous fat, respectively (P<0.05). The meat from the animals receiving RPF
      had greater C18:1 content (P<0.01). The CLA and C18:2 contents were greater in
      the LD muscle of the animals fed SB (P<0.01). However, alpha-C18:3 was greater in
      the LD muscle of animals fed RPF (P<0.01). In the subcutaneous fat, SB reduced
      C12:0 and C14:0 contents (P<0.01) and increased C18:0 (P<0.05). The inclusion of
      RPF increased the C18:1 and CLA contents (P<0.01) in the subcutaneous fat.
      Soybean elevated PUFA contents and increased susceptibility of muscle and
      subcutaneous fat to lipid oxidation.

PMID- 24018279
TI  - [Sinusal reversion of atrial flutter after intravenous propofol administration].

PMID- 24018280
TI  - [In-hospital prognostic value of functional assessment using the Barthel index in
      patients with acute coronary syndrome: initial evaluation of the nurse in the
      cardiac intensive care unit].

PMID- 24018282
TI  - Gender difference in calcification diseases: is it the result of gender-specific
      ways of nano-bacterial expansion?
AB  - Gender difference has been reported for frequency of the calcification diseases
      in urogenital system: according to published statistics data, they are more
      numerous in males. We suggest that the male increasing is due to nanobacterial
      infections and ways of their dissemination. There are specific gender-dependent
      ways for these infections which bring infection to the different target organs,
      namely: urinary tract, kidney, prostate in men and placenta in women.
      Identification of the suggested microbial pathogens and investigation of sex
      determined pathways for the dissemination are the following steps to get
      ascertaining events of gender reasons for different calcification diseases. 

PMID- 24018283
TI  - Topical tacrolimus nanoemulsion, a promising therapeutic approach for uveitis.
AB  - Uveitis is a sight threatening inflammatory disorder that affects all ages and
      remains a significant cause of visual loss. Inflammatory activity plays an
      important role in the whole pathogenesis of uveitis. Treatment of uveitis is
      mainly driven by corticosteroids that have potential side effects. Recent
      investigations demonstrated that tacrolimus inhibits T-cell proliferation and
      suppresses release of inflammatory cytokines. Since tacrolimus is a definite
      immunosuppressive agent, and since inflammatory process has been involved in
      uveitis, the compound must have effect on the progression of uveitis through
      reduction in inflammatory activity. Even results of the clinical trials
      demonstrate that tacrolimus have useful role in treatment of sight threatening
      uveitis that is refractory to other therapy. Studies also indicate that long term
      use of tacrolimus is well tolerated. However, its use in uveitis is limited
      because of its poor physico-chemical properties including poor aqueous solubility
      and high molecular weight (822 Da). Therefore, we have proposed that tacrolimus
      nanoemulsion administered topically is a promising therapeutic approach to treat
      uveitis. Based on previous evidences, we have hypothesized that nanoemulsion
      formulation of tacrolimus can improve efficacy and safety profile of tacrolimus.

PMID- 24018281
TI  - [Mitochondrial and microcirculatory distress syndrome in the critical patient.
      Therapeutic implications].
AB  - Mitochondrial and microcirculatory distress syndrome (MMDS) can occur during
      systemic inflammatory response syndrome (SIRS), and is characterized by
      cytopathic tissue hypoxia uncorrected by oxygen transport optimization, and
      associated with an acquired defect in the use of oxygen and energy production in
      mitochondria, leading to multiple organ dysfunction (MOD). We examine the
      pathogenesis of MMDS, new diagnostic methods, and recent therapeutic approaches
      adapted to each of the three phases in the evolution of the syndrome. In the
      initial phase, the aim is prevention and early reversal of mitochondrial
      dysfunction. Once the latter is established, the aim is to restore flow of the
      electron chain, mitochondrial respiration, and to avoid cellular energy collapse.
      Finally, in the third (resolution) stage, treatment should focus on stimulating
      mitochondrial biogenesis and the repair or replacement of damaged mitochondria.

PMID- 24018284
TI  - In silico design of small peptide-based Hsp90 inhibitor: a novel anticancer
      agent.
AB  - BACKGROUND: Breast cancer is a common disease found among women and has been a
      serious issue for last two decades. Although various kinds of heat shock proteins
      (Hsp's) have strong implications in cancer, heat shock protein 90 alpha
      (Hsp90alpha) has attracted highest attention for the cause and therapy of breast
      cancer. It regulates approximately 200 numbers of proteins known as client
      proteins including large number of oncoproteins found to be upregulated in many
      cancer cells. Therefore, inhibition of Hsp90alpha is a common therapeutic
      approach pursued in many cancers. However, Hsp90alpha inhibitors both natural and
      chemical, reported so far are plagued with problems related to toxicity,
      bioavailability and solubility including geldanamycin, the most common Hsp90alpha
      inhibitor. Therefore, search for a suitable Hsp90alpha inhibitor is an urgent
      need. HYPOTHESIS: Here we hypothesize that Hsp organizing protein (HOP) helps in
      the interaction of Hsp90alpha with Hsp70, which is the key to appropriate
      chaperonin function of Hsp90alpha and therefore, inhibiting such interaction
      might lead to the disruption of Hsp90alpha-client protein complex, which in turn
      destabilize and degrade client proteins. We further hypothesize that considering
      the residues involved in the reaction we can design novel peptide based
      Hsp90alpha inhibitor. EXPERIMENTAL DESIGN: In our present in silico
      investigation, we hypothesized that the chaperone function of Hsp90alpha requires
      the complex formation with HOP and co-chaperones Hsp70, Hsp40. We performed the
      docking interaction between Hsp90alpha and HOP. Based on the key residues
      involved in the interaction between Hsp90alpha and HOP, we designed ten peptides
      having twelve amino acids each. We docked the designed peptides with Hsp90alpha
      using docking software Hex 6.1 and the peptide with the highest binding energy
      value was identified. Using the online FOLDAMYLOID program, we assessed their
      amyloidogenic propensity. Amylodegenic properties were also considered and based
      on that five different peptides were again redesigned. Several modifications
      incorporated onto the peptide led to the design of five different peptides.
      RESULTS: The peptide with the lowest amyloidogenic properties and highest binding
      energy for Hsp90alpha was the criteria laid for selection as an Hsp90alpha
      inhibitor. Its potential to bind Hsp90alpha and disrupt Hsp90alpha-HOP complex
      was subsequently investigated using both wild as well as mutant p53 as a client
      protein. CONCLUSION: The predicted binding energy values showed that our designed
      novel peptide demonstrated strong binding affinity for Hsp90alpha. Subsequently,
      the binding affinity of Hsp90alpha for mutant p53 was shown to be reduced
      substantially indicating a strong inhibitory potential of the designed peptide
      PEP73 (INSAYKLKYARG) for Hsp90alpha.

PMID- 24018285
TI  - Unique variation in genetic selection among Black North American women and its
      potential influence on pregnancy outcome.
AB  - We hypothesize that variations in the frequency of genetic polymorphisms,
      reflecting ancestral differences in living conditions and exposure to
      microorganisms, increase susceptibility to adverse pregnancy outcome among
      present day Black North American women. Striking differences were observed in the
      frequency of genetic variants between Black and White or Hispanic women in 5
      genes (IL1RN, MBL2, PPARA, ATG16L1, CIAS1) associated with inflammation and anti
      microbial immunity. The CIAS1 and IL1RN polymorphisms were associated with
      altered interleukin-1beta serum levels; the MBL2 polymorphism resulted in a
      decreased serum mannose-binding lectin concentration. Gene polymorphisms
      associated with an alteration in innate immunity were most frequent in Black
      women. This may reflect an evolutionary selection in response to an ancient
      environment containing a high multitude of microorganisms, and may increase
      susceptibility of Black women to infection-associated preterm birth in the
      current North American environment. 

PMID- 24018286
TI  - Atrial ganglionated plexi stimulation may be an effective therapeutic tool for
      the treatment of heart failure.
AB  - An autonomic imbalance, i.e., increased sympathetic tone and/or decreased
      parasympathetic tone is a critical characteristic of heart failure, which is
      associated with progressive ventricular remodeling, ventricular arrhythmia
      generation and disease progression. Increasing cardiac parasympathetic tone by
      vagus nerve stimulation has been shown to significantly improve heart failure
      symptoms, hemodynamics, left ventricular function and quality of life. However,
      cervical surgery is needed to position vagal stimulation electrode and vagus
      nerve stimulation may also cause some undesired side effects. Our recent studies
      showed that ablation of the main atrial ganglionated plexi (GP) facilitated the
      occurrence of ventricular arrhythmias in acute myocardial ischemic heart while
      low-intensity atrial GP stimulation inhibited the occurrence of ventricular
      arrhythmias during acute myocardial ischemia and ischemia reperfusion. Based on
      these results, we hypothesize that atrial GP stimulation may ameliorate autonomic
      dysfunction in heart failure, inhibit heart failure progression and improve heart
      failure prognosis. 

PMID- 24018287
TI  - Epitope mapping and characterization of a neutralizing monoclonal antibody
      against human adenovirus type 3.
AB  - Human adenovirus serotype 3 (HAdV-3) has occurred as a global epidemic in recent
      years causing serious diseases such as pneumonia in pediatric and adult patients.
      Development of reliable diagnostic reagents and identification of neutralizing
      epitopes is important for the surveillance and control of infection. In this
      study, a neutralizing monoclonal antibody (MAb) MAb 1B6 was generated using the
      HAdV-3 virion. MAb 1B6 specially recognized the HAdV-3 virus particles and the
      HAdV-3 hexon protein, but not the virus particles or the hexon protein of HAdV-7
      and HAdV-4 by western-blot analysis and indirect enzyme-linked immunosorbent
      assay (ELISA). Analysis using a series of peptides from the hexon protein and
      chimeric adenovirus (Ad) particles of epitope mutants revealed that MAb 1B6 bound
      to the exposed region (amino acid positions 414-424 of hexon) in hypervariable
      region 7 (HVR7). ELISA demonstrated that MAb 1B6 could recognize the
      corresponding regions of other HAdV-3 genotypes that have some residues
      substituted. The identification of the neutralizing epitope and the generation of
      MAb 1B6 may be useful for clinical serotype-specific diagnosis, subunit vaccine
      construction for HAdV-3 infection, and virion structural analysis.

PMID- 24018289
TI  - Shotgun brain proteomics reveals early molecular signature in presymptomatic
      mouse model of Alzheimer's disease.
AB  - AbetapE3-42 (N-terminal truncated amyloid-beta peptide starting with
      pyroglutamate at the third position) is abundant in Alzheimer's disease (AD)
      brain and has high aggregation propensity and cellular toxicity. Transgenic TBA42
      mice expressing AbetapE3-42 exhibit a neurological phenotype evident at the age
      of 12 months. As AD has a long presymptomatic period, early detection of imminent
      neurodegeneration is highly desirable. In the present work we used four-month-old
      presymptomatic TBA42 mice and performed a whole-brain proteome analysis in order
      to elucidate early AD-related pathological changes and the molecular networks
      involved. At least three proteins were found to be moderately (by 17% to 28%) but
      statistically significantly upregulated, including: nectin-like molecule 1
      involved in cell-cell adhesion; Homer proteins involved in scaffolding,
      organizing proteins at synapse and regulating intracellular calcium within
      neurons; and inositol-trisphosphate 3-kinase A, which is important for InsP3
      induced calcium signaling in the brain. Analysis of key nodes (regulatory
      molecules found on pathway intersections) identified Rho-kinase (ROCK), a
      serine/threonine kinase and one of the major downstream effectors of the small
      GTPase Rho, as well as three key nodes of the mTOR/p70S6K signaling pathway
      previously implicated in multiple fundamental biological processes including
      synaptic plasticity, and upregulated in AD. These data confirm that AD-typical
      molecular pathways can be detected by whole-brain shotgun proteomics in young
      presymptomatic mice long before the onset of behavioral changes. 

PMID- 24018288
TI  - Burst suppression probability algorithms: state-space methods for tracking EEG
      burst suppression.
AB  - OBJECTIVE: Burst suppression is an electroencephalogram pattern in which bursts
      of electrical activity alternate with an isoelectric state. This pattern is
      commonly seen in states of severely reduced brain activity such as profound
      general anesthesia, anoxic brain injuries, hypothermia and certain developmental
      disorders. Devising accurate, reliable ways to quantify burst suppression is an
      important clinical and research problem. Although thresholding and segmentation
      algorithms readily identify burst suppression periods, analysis algorithms
      require long intervals of data to characterize burst suppression at a given time
      and provide no framework for statistical inference. APPROACH: We introduce the
      concept of the burst suppression probability (BSP) to define the brain's
      instantaneous propensity of being in the suppressed state. To conduct dynamic
      analyses of burst suppression we propose a state-space model in which the
      observation process is a binomial model and the state equation is a Gaussian
      random walk. We estimate the model using an approximate expectation maximization
      algorithm and illustrate its application in the analysis of rodent burst
      suppression recordings under general anesthesia and a patient during induction of
      controlled hypothermia. MAIN RESULT: The BSP algorithms track burst suppression
      on a second-to-second time scale, and make possible formal statistical
      comparisons of burst suppression at different times. SIGNIFICANCE: The state
      space approach suggests a principled and informative way to analyze burst
      suppression that can be used to monitor, and eventually to control, the brain
      states of patients in the operating room and in the intensive care unit.

PMID- 24018291
TI  - Semiconductor diode characterization for total skin electron irradiation.
AB  - In this paper, a semiconductor diode characterization was performed. The diode
      characterization was completed using an electron beam with 4 MeV of energy. The
      semiconductor diode calibration used irradiation with an electron beam in an ion
      chamber. "In vivo" dosimetry was also conducted. The dosimetry results revealed
      that the semiconductor diode was a good candidate for use in the total skin
      electron therapy (TSET) treatment control. 

PMID- 24018292
TI  - Dynamics of additional food provided predator-prey system with mutually
      interfering predators.
AB  - Use of additional/alternative food source to predators is one of the widely
      recognised practices in the field of biological control. Both theoretical and
      experimental works point out that quality and quantity of additional food play a
      vital role in the controllability of the pest. Theoretical studies carried out
      previously in this direction indicate that incorporating mutual interference
      between predators can stabilise the system. Experimental evidence also point out
      that mutual interference between predators can affect the outcome of the
      biological control programs. In this article dynamics of additional food provided
      predator-prey system in the presence of mutual interference between predators has
      been studied. The mutual interference between predators is modelled using
      Beddington-DeAngelis type functional response. The system analysis highlights the
      role of mutual interference on the success of biological control programs when
      predators are provided with additional food. The model results indicate the
      possibility of stable coexistence of predators with low prey population levels.
      This is in contrast to classical predator-prey models wherein this stable co
      existence at low prey population levels is not possible. This study classifies
      the characteristics of biological control agents and additional food (of suitable
      quality and quantity), permitting the eco-managers to enhance the success rate of
      biological control programs. 

PMID- 24018293
TI  - Spatial spread of an epidemic through public transportation systems with a hub.
AB  - This article investigates an epidemic spreading among several locations through a
      transportation system, with a hub connecting these locations. Public
      transportation is not only a bridge through which infections travel from one
      location to another but also a place where infections occur since individuals are
      typically in close proximity to each other due to the limited space in these
      systems. A mathematical model is constructed to study the spread of an infectious
      disease through such systems. A variant of the next generation method is proposed
      and used to provide upper and lower bounds of the basic reproduction number for
      the model. Our investigation indicates that increasing transportation efficiency,
      and improving sanitation and ventilation of the public transportation system
      decrease the chance of an outbreak occurring. Moreover, discouraging unnecessary
      travel during an epidemic also decreases the chance of an outbreak. However,
      reducing travel by infectives while allowing susceptibles to travel may not be
      enough to avoid an outbreak. 

PMID- 24018294
TI  - Non-identifiability of the Rayleigh damping material model in magnetic resonance
      elastography.
AB  - Magnetic Resonance Elastography (MRE) is an emerging imaging modality for
      quantifying soft tissue elasticity deduced from displacement measurements within
      the tissue obtained by phase sensitive Magnetic Resonance Imaging (MRI)
      techniques. MRE has potential to detect a range of pathologies, diseases and
      cancer formations, especially tumors. The mechanical model commonly used in MRE
      is linear viscoelasticity (VE). An alternative Rayleigh damping (RD) model for
      soft tissue attenuation is used with a subspace-based nonlinear inversion (SNLI)
      algorithm to reconstruct viscoelastic properties, energy attenuation mechanisms
      and concomitant damping behavior of the tissue-simulating phantoms. This research
      performs a thorough evaluation of the RD model in MRE focusing on unique
      identification of RD parameters, MUI and rhoI. Results show the non
      identifiability of the RD model at a single input frequency based on a structural
      analysis with a series of supporting experimental phantom results. The estimated
      real shear modulus values (MUR) were substantially correct in characterising
      various material types and correlated well with the expected stiffness contrast
      of the physical phantoms. However, estimated RD parameters displayed consistent
      poor reconstruction accuracy leading to unpredictable trends in parameter
      behaviour. To overcome this issue, two alternative approaches were developed: (1)
      simultaneous multi-frequency inversion; and (2) parametric-based reconstruction.
      Overall, the RD model estimates the real shear shear modulus (MUR) well, but
      identifying damping parameters (MUI and rhoI) is not possible without an
      alternative approach. 

PMID- 24018295
TI  - Journal of Critical Care. Editorial.

PMID- 24018296
TI  - How to select an antifungal agent in critically ill patients.
AB  - Fungal infections are common in critically ill patients and are associated with
      increased morbidity and mortality. Candida spp are the most commonly isolated
      fungal pathogens. The last 2 decades have seen an increased incidence of fungal
      infections in critical illness and the emergence of new pathogenic fungal species
      and also the development of more effective (better bioavailability) and safer
      (less toxicity, fewer drug interactions) drugs. The distinction between
      colonization and infection can be difficult, and problems diagnosing infection
      may delay initiation of antifungal treatment. A number of factors have been
      identified that can help to distinguish patients at high risk for fungal
      infection. The antifungal agents that are most frequently used in the intensive
      care unit are the first- and second-generation azoles and the echinocandins;
      amphotericin B derivatives (mainly the liposomal agents) are less widely used
      because of adverse effects. The choice of antifungal agent in critically ill
      patients will depend on the aim of therapy (prophylaxis, pre-emptive, empiric,
      definitive), as well as on local epidemiology and specific properties of the drug
      (antifungal spectrum, efficacy, toxicity, pharmacokinetic/pharmacodynamic
      properties, cost). In this article we will review all these aspects and propose
      an algorithm to guide selection of antifungal agents in critically ill patients. 

PMID- 24018298
TI  - There and back again, the value of translational research.

PMID- 24018297
TI  - Is vitamin D deficiency associated with development of Acinetobacter baumannii
      infections in critically ill patients?
AB  - PURPOSE: A growing number of evidence demonstrates deficiency of vitamin D in
      critically ill patients. We aimed to evaluate the vitamin D status of our
      critically ill patients and its relevance to infections in these patients.
      MATERIAL AND METHODS: We conducted a prospective observational study in 201
      critically ill patients admitted to the medical intensive care unit of Gazi
      University Hospital between October 2009 through March 2011. RESULTS: Sixty-nine
      percent of the patients were found to be vitamin D deficient. Infection rate was
      higher in the deficient group, though without statistical significance (P=.117).
      Infections with Acinetobacter baumannii was significantly more frequent in
      patients with Vitamin D deficiency (25% vs 10%, P=.012). The median level of 25
      hydroxyvitamin D levels was 11.8 [6.3-17.2] ng/mL and 15.7 [8.1-28.9] ng/mL in
      patients with and without A baumannii infections respectively (P=.024). Logistic
      regression analysis demonstrated that vitamin D deficiency (P=.042) and invasive
      mechanical ventilation (P=.001) were the 2 independent risk factors in the
      development of A baumannii infections, in addition. CONCLUSIONS: Vitamin D
      deficiency is common in critically ill patients. Even though there was no
      statistical difference between vitamin D deficient and sufficient patients
      regarding development of infections in general, A baumannii infections were
      significantly more frequent in the deficient group. Vitamin D deficiency was
      found as one of the independent risk factors for A baumannii infections. Further
      multicenter studies with a larger sample size are required to validate our data.

PMID- 24018299
TI  - I-TRACH, you-TRACH, we all-TRACH for....?

PMID- 24018300
TI  - Mechanical ventilation outside intensive care unit. A growing demand in a
      vulnerable population. Are there possible solutions?

PMID- 24018301
TI  - Molecular analysis of a novel Toll/interleukin-1 receptor (TIR)-domain containing
      virulence protein of Y. pseudotuberculosis among Far East scarlet-like fever
      serotype I strains.
AB  - Pathogenicity of Yersinia pseudotuberculosis is determined by an arsenal of
      virulence factors. Particularly, the Yersinia outer proteins (Yops) and the Type
      III secretion system (T3SS) encoded on the pYV virulence plasmid are required for
      Yersinia pathogenicity. A specific group of Y. pseudotuberculosis, responsible
      for the clinical syndrome described as Far East scarlet-like fever (FESLF), is
      known to have an altered virulence gene cluster. Far East strains cause unique
      clinical symptoms for which the pYV virulence plasmid plays apparently a rather
      secondary role. Here, we characterize a previously unknown protein of Y.
      pseudotuberculosis serotype I strains (TcpYI) which can be found particularly
      among the FESLF strain group. The TcpYI protein shares considerable sequence
      homology to members of the Toll/IL-1 receptor family. Bacterial TIR domain
      containing proteins (Tcps) interact with the innate immune system by TIR-TIR
      interactions and subvert host defenses via individual, multifaceted mechanisms.
      In terms of virulence, it appears that the TcpYI protein of Y. pseudotuberculosis
      displays its own virulence phenotype compared to the previously characterized
      bacterial Tcps. Our results clearly demonstrate that TcpYI increases the
      intracellular survival of the respective strains in vitro. Furthermore, we show
      here that the intracellular survival benefit of the wild-type strain correlates
      with an increase in tcpYI gene expression inside murine macrophages. In support
      of this, we found that TcpYI enhances the survival inside the spleens of mice in
      a mouse model of peritonitis. Our results may point toward involvement of the
      TcpYI protein in inhibition of phagocytosis, particularly in distinct Y.
      pseudotuberculosis strains of the FESLF strain group where the pYV virulence
      plasmid is absent. 

PMID- 24018303
TI  - Bayesian model selection for group studies - revisited.
AB  - In this paper, we revisit the problem of Bayesian model selection (BMS) at the
      group level. We originally addressed this issue in Stephan et al. (2009), where
      models are treated as random effects that could differ between subjects, with an
      unknown population distribution. Here, we extend this work, by (i) introducing
      the Bayesian omnibus risk (BOR) as a measure of the statistical risk incurred
      when performing group BMS, (ii) highlighting the difference between random
      effects BMS and classical random effects analyses of parameter estimates, and
      (iii) addressing the problem of between group or condition model comparisons. We
      address the first issue by quantifying the chance likelihood of apparent
      differences in model frequencies. This leads to the notion of protected
      exceedance probabilities. The second issue arises when people want to ask
      "whether a model parameter is zero or not" at the group level. Here, we provide
      guidance as to whether to use a classical second-level analysis of parameter
      estimates, or random effects BMS. The third issue rests on the evidence for a
      difference in model labels or frequencies across groups or conditions. Overall,
      we hope that the material presented in this paper finesses the problems of group
      level BMS in the analysis of neuroimaging and behavioural data. 

PMID- 24018302
TI  - Visualization of intra-thalamic nuclei with optimized white-matter-nulled MPRAGE
      at 7T.
AB  - Novel MR image acquisition strategies have been investigated to elicit contrast
      within the thalamus, but direct visualization of individual thalamic nuclei
      remains a challenge because of their small size and the low intrinsic contrast
      between adjacent nuclei. We present a step-by-step specific optimization of the
      3D MPRAGE pulse sequence at 7T to visualize the intra-thalamic nuclei. We first
      measured T1 values within different sub-regions of the thalamus at 7T in 5
      individuals. We used these to perform simulations and sequential experimental
      measurements (n=17) to tune the parameters of the MPRAGE sequence. The optimal
      set of parameters was used to collect high-quality data in 6 additional
      volunteers. Delineation of thalamic nuclei was performed twice by one rater and
      MR-defined nuclei were compared to the classic Morel histological atlas. T1
      values within the thalamus ranged from 1400ms to 1800ms for adjacent nuclei.
      Using these values for theoretical evaluations combined with in vivo
      measurements, we showed that a short inversion time (TI) close to the white
      matter null regime (TI=670ms) enhanced the contrast between the thalamus and the
      surrounding tissues, and best revealed intra-thalamic contrast. At this
      particular nulling regime, lengthening the time between successive inversion
      pulses (TS=6000ms) increased the thalamic signal and contrast and lengthening the
      alpha pulse train time (N*TR) further increased the thalamic signal. Finally, a
      low flip angle during the gradient echo acquisition (alpha=4 degrees ) was
      observed to mitigate the blur induced by the evolution of the magnetization along
      the alpha pulse train. This optimized set of parameters enabled the 3D
      delineation of 15 substructures in all 6 individuals; these substructures
      corresponded well with the known anatomical structures of the thalamus based on
      the classic Morel atlas. The mean Euclidean distance between the centers of mass
      of MR- and Morel atlas-defined nuclei was 2.67mm (+/-1.02mm). The reproducibility
      of the MR-defined nuclei was excellent with intraclass correlation coefficient
      measured at 0.997 and a mean Euclidean distance between corresponding centers of
      mass found at first versus second readings of 0.69mm (+/-0.38mm). This 7T
      strategy paves the way to better identification of thalamic nuclei for
      neurosurgical planning and investigation of regional changes in neurological
      disorders. 

PMID- 24018304
TI  - Reliability measures of functional magnetic resonance imaging in a longitudinal
      evaluation of mild cognitive impairment.
AB  - As the aging population grows, it has become increasingly important to carefully
      characterize amnestic mild cognitive impairment (aMCI), a preclinical stage of
      Alzheimer's disease (AD). Functional magnetic resonance imaging (fMRI) is a
      valuable tool for monitoring disease progression in selectively vulnerable brain
      regions associated with AD neuropathology. However, the reliability of fMRI data
      in longitudinal studies of older adults with aMCI is largely unexplored. To
      address this, aMCI participants completed two visual working tasks, a Delayed
      Recognition task and a One-Back task, on three separate scanning sessions over a
      three-month period. Test-retest reliability of the fMRI blood oxygen level
      dependent (BOLD) activity was assessed using an intraclass correlation (ICC)
      analysis approach. Results indicated that brain regions engaged during the task
      displayed greater reliability across sessions compared to regions that were not
      utilized by the task. During task-engagement, differential reliability scores
      were observed across the brain such that the frontal lobe, medial temporal lobe,
      and subcortical structures exhibited fair to moderate reliability (ICC=0.3-0.6),
      while temporal, parietal, and occipital regions exhibited moderate to good
      reliability (ICC=0.4-0.7). Additionally, reliability across brain regions was
      more stable when three fMRI sessions were used in the ICC calculation relative to
      two fMRI sessions. In conclusion, the fMRI BOLD signal is reliable across
      scanning sessions in this population and thus a useful tool for tracking
      longitudinal change in observational and interventional studies in aMCI. 

PMID- 24018306
TI  - Anatomical connectivity changes in the bilingual brain.
AB  - How the brain deals with more than one language and whether we need different or
      extra brain language sub-networks to support more than one language remain
      unanswered questions. Here, we investigate structural brain network differences
      between early bilinguals and monolinguals. Using diffusion-weighted MRI (DW-MRI)
      tractography techniques and a network-based statistic (NBS) procedure, we found
      two structural sub-networks more connected by white matter (WM) tracts in
      bilinguals than in monolinguals; confirming WM brain plasticity in bilinguals.
      One of these sub-networks comprises left frontal and parietal/temporal regions,
      while the other comprises left occipital and parietal/temporal regions and also
      the right superior frontal gyrus. Most of these regions have been related to
      language processing and monitoring; suggesting that bilinguals develop
      specialized language sub-networks to deal with the two languages. Additionally, a
      complex network analysis showed that these sub-networks are more graph-efficient
      in bilinguals than monolinguals and this increase seems to be at the expense of a
      whole-network graph-efficiency decrease. 

PMID- 24018305
TI  - Broadband changes in the cortical surface potential track activation of
      functionally diverse neuronal populations.
AB  - We illustrate a general principal of electrical potential measurements from the
      surface of the cerebral cortex, by revisiting and reanalyzing experimental work
      from the visual, language and motor systems. A naive decomposition technique of
      electrocorticographic power spectral measurements reveals that broadband spectral
      changes reliably track task engagement. These broadband changes are shown to be a
      generic correlate of local cortical function across a variety of brain areas and
      behavioral tasks. Furthermore, they fit a power-law form that is consistent with
      simple models of the dendritic integration of asynchronous local population
      firing. Because broadband spectral changes covary with diverse perceptual and
      behavioral states on the timescale of 20-50 ms, they provide a powerful and
      widely applicable experimental tool.

PMID- 24018307
TI  - Optimizing RetroICor and RetroKCor corrections for multi-shot 3D FMRI
      acquisitions.
AB  - Physiological noise, if unaccounted for, can drastically reduce the statistical
      significance of detected activation in FMRI. In this paper, we systematically
      optimize physiological noise regressions for multi-shot 3D FMRI data. First, we
      investigate whether 3D FMRI data are best corrected in image space (RetroICor) or
      k-space (RetroKCor), in which each k-space segment can be assigned its unique
      physiological phase. In addition, the optimal regressor set is determined using
      the Bayesian Information Criterion (BIC) for a variety of 3D acquisitions
      corresponding to different image contrasts and k-space readouts. Our simulations
      and experiments indicate that: (a) k-space corrections are more robust when
      performed on real/imaginary than magnitude/phase data; (b) k-space corrections do
      not outperform image-space corrections, despite the ability to synchronize
      physiological phase to acquisition time more accurately; and (c) the optimal
      model varied considerably between the various acquisition techniques. These
      results suggest the use of a tailored set of volume-wide regressors, determined
      by BIC or other selection criteria, that achieves optimal balance between
      variance reduction and potential over-fitting. 

PMID- 24018308
TI  - The use of a comparability scoring system in reporting observational studies.
AB  - The traditional statistical analyses with adjustment for confounders in
      observational studies assume that there is perfect similarity in the already
      provided medical management between the comparison groups. However, variations in
      medical management frequently exist because of differences in circumstances of
      health care. We propose that to minimize the selection bias of observational
      studies, the degree of similarity or dissimilarity of the comparison groups
      regarding the circumstances of health care should be considered. Circumstances of
      health care include the geographic setting, health care setting, type of health
      care providers, and likelihood in having confounding introduced by differences in
      the medical management between comparison groups. We propose a comparability
      scoring system of circumstances of care and provide examples of the application
      of this system, using recent literature to assess comparability among study
      groups. In our examples, the presupposed statistical associations disappeared
      once the analyses accounted for the differences in circumstances of care. Authors
      of submitted manuscripts using an observational study design may consider
      incorporating our scoring system or an equivalent in their methods and in
      reporting of the results. The comparability score should be factored during
      statistical analysis so that the appropriate analysis can correct for differences
      in circumstances of care. The use of a comparability scoring system can provide
      important insights for reviewers and readers that will improve the interpretation
      of this type of research study. 

PMID- 24018309
TI  - The impact of Centering Pregnancy Group Prenatal Care on postpartum family
      planning.
AB  - OBJECTIVE: The objective of the study was to evaluate the impact of group
      prenatal care (GPNC) on postpartum family-planning utilization. STUDY DESIGN: A
      retrospective cohort of women continuously enrolled in Medicaid for 12 months (n
      = 3637) was used to examine differences in postpartum family-planning service
      utilization among women participating in GPNC (n = 570) and those receiving
      individual prenatal care (IPNC; n = 3067). Propensity scoring methods were used
      to derive a matched cohort for additional analysis of selected outcomes. RESULTS:
      Utilization of postpartum family-planning services was higher among women
      participating in GPNC than among women receiving IPNC at 4 points in time: 3
      (7.72% vs 5.15%, P < .05), 6 (22.98% vs 15.10%, P < .05), 9 (27.02% vs 18.42%, P
      < .05), and 12 (29.30% vs 20.38%, P < .05) months postpartum. Postpartum family
      planning visits were highest among non-Hispanic black women at each interval,
      peaking with 31.84% by 12 months postpartum. After propensity score matching,
      positive associations between GPNC and postpartum family-planning service
      utilization remained consistent by 6 (odds ratio [OR], 1.42; 95% confidence
      interval [CI], 1.05-1.92), 9 (OR, 1.43; 95% CI, 1.08-1.90), and 12 (OR, 1.44; 95%
      CI, 1.10-1.90) months postpartum. CONCLUSION: These findings demonstrate the
      potential that GPNC has to positively influence women's health outcomes after
      pregnancy and to improve the utilization rate of preventive health services.
      Utilization of postpartum family-planning services was highest among non-Hispanic
      black women, further supporting evidence of the impact of GPNC in reducing health
      disparities. However, despite continuous Medicaid enrollment, postpartum
      utilization of family-planning services remained low among all women, regardless
      of the type of prenatal care they received.

PMID- 24018310
TI  - Oxygen uptake and energy expenditure for children during rock climbing activity.
AB  - The purpose of this study was to measure oxygen uptake and energy expenditure in
      children during rock climbing activity. 29 children (age = 10.9 +/- 1.7 yr)
      participated in the study. A commercially available rock climbing structure with
      ample features for submaximal effort climbing provided continuous terrain.
      Participants were instructed to climb at a comfortable pace. Following an initial
      5-min rest, each child climbed one sustained 5-min bout followed by 5-min sitting
      recovery for a total of 10 min (SUS). This was immediately followed by five 1-min
      climbing + 1-min recovery intervals for a second total of 10 min (INT). Expired
      air was analyzed continuously. Energy expenditure (EE) was determined via the
      Weir method for 10-s intervals throughout the full protocol. The total energy
      expenditure in kilocalories during the 10-min SUS period was 34.3 +/- 11.3 kcal.
      Energy expenditure during the 10-min INT period averaged 39.3 +/- 13.1 kcal and
      was significantly higher than during SUS (p < .05). The mean total EE for SUS +
      INT was 73.7 +/- 24.2 kcal. EE was correlated with body mass; r = .86. The rock
      climbing tasks employed in this study produced EE levels similar to what have
      been reported in children for stair climbing, sports/games activities, and easy
      jogging. 

PMID- 24018311
TI  - Staphylococcus aureus and Escherichia coli elicit different innate immune
      responses from bovine mammary epithelial cells.
AB  - Escherichia coli and Staphylococcus aureus are the most important pathogenic
      bacteria causing bovine clinical mastitis and subclinical mastitis, respectively.
      However, little is known about the molecular mechanisms underlying the different
      host response patterns caused by these bacteria. The aim of this study was to
      characterize the different innate immune responses of bovine mammary epithelium
      cells (MECs) to heat-inactivated E. coli and S. aureus. Gene expression of Toll
      like receptor 2 (TLR2) and TLR4 was compared. The activation of nuclear factor
      kappa B (NF-kappaB) and the kinetics and levels of cytokine production were
      analyzed. The results show that the mRNA for TLR2 and TLR4 was up-regulated when
      the bovine MECs were stimulated with heat-inactivated E. coli, while only TLR2
      mRNA was up-regulated when the bovine MECs were stimulated with heat-inactivated
      S. aureus. The expression of tumor necrosis factor-alpha (TNF-alpha), interleukin
      (IL)-1beta, IL-6 and IL-8 increased more rapidly and higher when the bovine MECs
      were stimulated with heat-inactivated E. coli than when they were stimulated with
      heat-inactivated S. aureus. E. coli strongly activated NF-kappaB in the bovine
      MECs, while S. aureus failed to activate NF-kappaB. Heat-inactivated S. aureus
      could induce NF-kappaB activation when bovine MECs cultured in medium without
      fetal calf serum. These results were confirmed using TLR2- and TLR4/MD2
      transfected HEK293 cells and suggested that differential TLR recognition and the
      lack of NF-kappaB activation account for the impaired immune response elicited by
      heat-inactivated S. aureus. 

PMID- 24018312
TI  - Macular spectral domain optical coherence tomography findings in Tanzanian
      endemic optic neuropathy.
AB  - Bilateral optic neuropathy in Dar es Salaam is now considered endemic and is
      estimated to affect 0.3-2.4% of young adults. The condition is characterized by a
      subacute bilateral loss of central vision of unknown aetiology. Findings of
      spectral domain optical coherence tomography have not previously been reported
      for these patients. All patients diagnosed with endemic optic neuropathy over a 2
      year period at the Muhimbili National Hospital underwent spectral domain optical
      coherence tomography macular imaging. Scans were graded qualitatively for
      severity of retinal nerve fibre layer loss as well as the presence of microcystic
      macular changes, which have not previously been described in this condition. Of
      the 128 patients included (54.7% male; median age 20 years), severe retinal nerve
      fibre layer loss was found in 185 eyes (74.0%). There was full concordance in
      retinal nerve fibre layer thickness between the two eyes in 113 (91.1%) patients.
      Microcystic macular spaces were found in 16 (12.5%) patients and were bilateral
      in nine (7.0%) individuals. These changes were typically more prominent in the
      nasal than the temporal macula, predominantly involving the inner nuclear layer,
      and often occurred in an annular configuration that was evident on en face infra
      red imaging, though not discernible on colour fundus photography or clinically.
      All patients with microcystic macular changes had severe thinning of the retinal
      nerve fibre layer (P = 0.02). Four patients in whom cystic spaces were
      demonstrated had sequential scans, and there was no detectable alteration in the
      configuration of these changes over a period of up to 16 months. This is the
      first study to document optical coherence tomography findings in endemic optic
      neuropathy. We have observed symmetrical severe loss of the caeco-central
      projection (papillomacular bundle) with otherwise well-preserved macular
      architecture. Also, we have observed microcystic retinal changes in a significant
      proportion of patients, which were associated with severe retinal nerve fibre
      layer loss. Similar changes have recently been reported from optical coherence
      tomography images of patients with multiple sclerosis, relapsing isolated optic
      neuritis, dominant optic atrophy, Leber's hereditary optic neuropathy and a
      patient with a chronic compressive optic neuropathy, supporting the hypothesis
      that this may be a non-specific phenomenon secondary to ganglion cell death. The
      correspondence of the changes to an annulus discernible on infra-red en face
      imaging, but not using other conventional retinal imaging techniques highlights
      the potential usefulness of this modality. 

PMID- 24018313
TI  - [Uncommon adverse effects after interferon therapy in patients with hepatitis C].

PMID- 24018314
TI  - Lack of the host membrane protease FtsH hinders release of the Lactococcus lactis
      bacteriophage TP712.
AB  - The temperate bacteriophage TP712 was unable to plaque on Lactococcus lactis
      DeltaftsH lacking the membrane protease FtsH and complementation in trans
      restored the WT phenotype. Absence of ftsH did not hinder phage adsorption, phage
      DNA delivery or activation of the lytic cycle. Thin sections revealed that TP712
      virions appeared to be correctly assembled inside the DeltaftsH host, but were
      not released. These virions were infective, demonstrating that a functional host
      FtsH is required by TP712 to proceed effectively with lysis of the host. 

PMID- 24018315
TI  - Characterization of self-assembled virus-like particles of ferret hepatitis E
      virus generated by recombinant baculoviruses.
AB  - Ferret hepatitis E virus (HEV), a novel hepatitis E-like virus, has been
      identified in ferrets in The Netherlands. Due to the lack of a cell-culture
      system for ferret HEV, the antigenicity, pathogenicity and epidemiology of this
      virus have remained unclear. In the present study, we used a recombinant
      baculovirus expression system to express the 112-N-terminus and 47-C-terminus
      amino-acid-truncated ferret HEV ORF2 protein in insect Tn5 cells, and found that
      a large amount of a 53 kDa protein (F-p53) was expressed and efficiently released
      into the supernatant. Electron microscopic analysis revealed that F-p53 was self
      assembled into virus-like particles (ferret HEV-LPs). These ferret HEV-LPs were
      estimated to be 24 nm in diameter, which is similar to the size of G1, G3, G4 and
      rat HEV-LPs derived from both the N-terminus- and C-terminus-truncated
      constructs. Antigenic analysis demonstrated that ferret HEV-LPs were cross
      reactive with G1, G3, G4 and rat HEVs, and rat HEV and ferret HEV showed a
      stronger cross-reactivity to each other than either did to human HEV genotypes.
      However, the antibody against ferret HEV-LPs does not neutralize G3 HEV,
      suggesting that the serotypes of these two HEVs are different. An ELISA for
      detection of anti-ferret HEV IgG and IgM antibodies was established using ferret
      HEV-LPs as antigen, and this assay system will be useful for monitoring ferret
      HEV infection in ferrets as well as other animals. In addition, analysis of
      ferret HEV RNA detected in ferret sera collected from a breeding colony in the
      USA revealed the genetic diversity of ferret HEV. 

PMID- 24018316
TI  - Dolutegravir does not affect methadone pharmacokinetics in opioid-dependent, HIV
      seronegative subjects.
AB  - BACKGROUND: Dolutegravir (DTG) is an investigational integrase inhibitor for
      treatment of HIV infection. As intravenous drug use is a common risk factor for
      HIV, this study evaluated the effect of DTG on the pharmacokinetics (PK) of
      methadone. METHODS: This was an open-label, 2-period study in adult, opioid
      dependent, HIV-seronegative subjects. Subjects received their current individual
      methadone doses once daily for 3 days (Period 1) followed by DTG 50mg twice daily
      (BID) for 5 days while continuing their stable methadone therapy (Period 2).
      Serial PK samples for R- and S-methadone were collected after each Period.
      Pharmacodynamic (PD) measures and safety assessments were obtained throughout the
      study. Non-compartmental PK analysis was performed, and geometric least-squares
      mean ratios and 90% confidence intervals were generated. RESULTS: Plasma
      exposures of total, R-, and S-methadone were not affected by co-administration of
      DTG. Mean ratios for AUC were 0.98, 0.95, and 1.01 for total, R-, and S
      methadone, respectively, alone compared with in combination with DTG. No
      statistically significant differences were noted between the 2 treatment periods
      in methadone PD measures. The combination of DTG and methadone was well
      tolerated. No deaths, serious adverse events, or grade 3/4 adverse events
      occurred. No clinically significant changes in laboratory values, vital signs, or
      electrocardiograms were observed. CONCLUSION: Co-administration of methadone with
      repeat doses of DTG 50mg BID had no effect on total, R-, and S-methadone PK or on
      methadone-induced PD markers. No dose adjustment in methadone is required when
      given in combination with DTG.

PMID- 24018317
TI  - Exercise increases plasma THC concentrations in regular cannabis users.
AB  - BACKGROUND: The major psychoactive ingredient of cannabis, Delta(9)
      tetrahydrocannabinol (THC) accumulates in fat tissue from where it slowly
      diffuses back into blood. THC pre-treated rats can show elevated plasma
      cannabinoid levels when subjected to conditions that promote fat utilization,
      such as fasting. Here we examine whether fasting and exercise increase plasma THC
      concentrations in regular cannabis users. METHODS: Fourteen regular cannabis
      users completed 35 min of exercise on a stationary bicycle in either a fed or
      overnight fasted state. Plasma cannabinoid levels were assessed prior to
      exercise, immediately post-exercise and 2h post-exercise. Plasma samples were
      also analyzed for indices of lipolysis (free fatty acids (FFA) and glycerol).
      RESULTS: Exercise induced a small, statistically significant increase in plasma
      THC levels accompanied by increased plasma FFA and glycerol levels. Exercise
      induced increases in plasma THC concentrations were positively correlated with
      body mass index. Fasting induced a significant increase in plasma FFA levels, and
      a lowering of blood glucose, but did not significantly alter plasma cannabinoid
      levels. CONCLUSIONS: Here we demonstrate that exercise enhances plasma THC levels
      in regular cannabis users. The lack of a fasting effect may reflect the modest
      duration of fasting used which was associated with only a modest increase in fat
      utilization relative to exercise. Overall, these results suggest that exercise
      may elevate blood THC levels by releasing dormant THC from fat stores. These data
      suggest the interpretation of blood THC levels in roadside and workplace tests
      might be complicated by recent exercise.

PMID- 24018318
TI  - Risk estimates for starting tobacco, alcohol, and other drug use in the United
      States: male-female differences and the possibility that 'limiting time with
      friends' is protective.
AB  - BACKGROUND: A specific facet of parental monitoring is known as 'limiting time
      with friends' (LTF). Here, we aim to learn whether LTF-associated differences in
      adolescent risk of starting to use tobacco, alcohol, and other drugs now might be
      as large as observed male-female risk differences. METHODS: Data are from the US
      National Surveys on Drug Use and Health, with annual large scale nationally
      representative samples of community-dwelling civilian age 12 years and older,
      conducted 2002-2009. Focus is on 12-17-year-old participants, assessed via
      computerized self-interviews. Risk differences are estimated for all 12-17 year
      olds, males and females separately, and in relation to the LTF facet of
      parenting. RESULTS: Contingency table analyses disclose a female excess risk of
      initiating use of tobacco, alcohol, cocaine, opioids, and EMIRD, with male-female
      risk differences ranging from 0.1% (cocaine) to 1.6% (alcohol). LTF-associated
      risk differences were of similar magnitude for young people whose parents
      'always' limit time with friends versus those with parents who are more relaxed
      about the LTF facet of parenting [e.g., RD=0.4% (cocaine); 1.5% (alcohol)].
      CONCLUSIONS: Not just for tobacco, but also for other drugs, there now is female
      excess risk of extra-medical drug use. Drug-by-drug, observed LTF-associated risk
      differences are about the same size as the female excess risk. This evidence
      provides a rationale to sustain focus on the LTF facet of parenting if the goal
      is to enhance prevention of precocious drug involvement and to delay its onset
      until later in the adolescent or adult years.

PMID- 24018319
TI  - Reply to: "Time is a crucial factor for the use of oncological treatment for post
      transplantation recurrence of hepatocellular carcinoma".

PMID- 24018320
TI  - Determination of metoprolol and its two metabolites in human plasma and urine by
      high performance liquid chromatography with fluorescence detection and its
      application in pharmacokinetics.
AB  - A simple, specific and sensitive HPLC method has been developed for the
      determination of metoprolol and its two metabolites in human plasma and urine.
      Separation of metoprolol, alpha-hydroxymetoprolol, O-desmethylmetoprolol and
      esmolol (internal standard) was achieved on an Agilent XDB-C18 column
      (150mm*4.6mm, 5MUm) using fluorescence detection with Ex 216nm and Em 312nm. The
      mobile phase consisted of ACN-H2O-0.1%TFA. The analysis was performed in less
      than 16min with a flow rate of 0.8mL/min. The assay was linear over the
      concentration range of 5-600ng/mL and 2.5-300ng/mL for metoprolol and its
      metabolites, respectively. The LOQ were 5.0 and 2.5ng/mL for plasma and urine,
      respectively. Good precision and accuracy for metoprolol and its two metabolites
      were obtained. The extraction recoveries were found to be more than 86.91% both
      in plasma and urine. At the same time, the method was successfully applied to
      nine healthy volunteers who had been given an oral tablet of 100mg metoprolol. 

PMID- 24018321
TI  - Studying biomacromolecules with two-dimensional infrared spectroscopy.
AB  - Two-dimensional infrared (2DIR) spectroscopy is a rapidly developing nonlinear
      spectroscopy, which allows access to greater structural detail than traditional
      vibrational spectroscopies. The ability to gain extra structural insight is
      particularly relevant to the study of biomacromolecules, whose Fourier transform
      infrared (FTIR) spectra are often congested, due to the large number of
      vibrations. The subpicosecond timescale of the spectroscopy gives the opportunity
      to follow the fluctuations of a molecule in the time domain. Theoretical and
      experimental techniques are well developed for 2DIR, and they have already given
      insight into some of the fundamental aspects of the structure and dynamics of
      proteins and nucleic acids. This chapter reviews some of these recent studies and
      showcases the potential of the method. 

PMID- 24018322
TI  - NMR studies on the dynamics of hydrogen bonds and ion pairs involving lysine side
      chains of proteins.
AB  - Hydrogen bonds and ion pairs involving side chains play vital roles in protein
      functions such as molecular recognition and catalysis. Despite the wealth of
      structural information about hydrogen bonds and ion pairs at functionally crucial
      sites on proteins, the dynamics of these fundamental chemical interactions are
      not well understood largely due to the lack of suitable experimental tools in the
      past. NMR spectroscopy is a powerful tool for investigations of protein dynamics,
      but the vast majority of NMR methods had been applicable only to the backbone or
      methyl groups. Recently, a substantial progress has been made in the research on
      the dynamics of hydrogen bonds and ion pairs involving lysine side-chain NH3+
      groups. Together with computational/theoretical approaches, the new NMR methods
      provide unique insights into the dynamics of hydrogen bonds and ion pairs
      involving lysine side chains. Here, the methodology and its applications are
      reviewed.

PMID- 24018323
TI  - Structure-function relationship of the plant photosynthetic pigment-protein
      complex LHCII studied with molecular spectroscopy techniques.
AB  - LHCII, the largest plant photosynthetic pigment-protein complex of photosystem
      II, is a most abundant membrane protein in living organisms and comprises
      approximately half of the pool of chlorophyll molecules in the biosphere. The
      principal role of this pigment-protein complex is to collect sunlight quanta and
      transfer electronic excitations toward the reaction centers, where the primary
      photosynthetic electric charge separation reactions take place. The LHCII
      protein, as a major protein component of the photosynthetic membranes, modulates
      also the structural and dynamic properties of the lipid phase of the membranes.
      According to the recent concepts, one of the physiological roles of LHCII is also
      a protection of the photosynthetic apparatus against oxidative damage caused by
      illumination with high intensity light. Detailed examination of all those
      physiological functions of LHCII, in relation to the complex structure, was
      possible owing to the application of several molecular spectroscopy techniques.
      Some examples of such studies are presented in this chapter. The examples of
      application of steady-state and time-resolved fluorescence spectroscopy, Fourier
      transform infrared absorption spectroscopy, and resonance Raman scattering
      spectroscopy are presented and discussed. 

PMID- 24018324
TI  - Combined use of optical spectroscopy and computational methods to study the
      binding and the photoinduced conformational modification of proteins when NMR and
      X-ray structural determinations are not an option.
AB  - The functions of proteins depend on their interactions with various ligands and
      these interactions are controlled by the structure of the polypeptides. If one
      can manipulate the structure of proteins, their functions can in principle be
      modulated. The issue of protein structure-function relationship is not only a
      central problem in biophysics, but is becoming clear that the ability to
      "artificially" modify the structure of proteins could be relevant in fields
      beyond the biomedical area to provide, for instance, light responses in proteins
      which would not possess such properties in their native state. This chapter
      presents an overview of the combination of optical electronic and vibrational
      spectroscopy with various computational methods to investigate the binding
      between photoactive ligands and proteins. 

PMID- 24018326
TI  - Protein and water confined in nanometer-scale reverse micelles studied by near
      infrared, terahertz, and ultrafast visible spectroscopies.
AB  - Protein-containing reverse (PCR) micelles are suitable systems to study the
      properties of proteins and waters in a cell-like environment. A model for
      determining the structural parameters of PCR micelles, such as the aqueous cavity
      size and molecule number of water within the reverse micelle, is presented. The
      model is based on an important hypothesis that the structural parameters of the
      protein-unfilled reverse micelle do not change after solubilization of protein. I
      describe a procedure using near infrared spectroscopy of OH stretching vibration
      band of water to verify the hypothesis. Further, the terahertz (THz) absorption
      spectrum of myoglobin is derived from THz time-domain spectroscopy of the PCR
      micellar solution, and the states of waters in reverse micelles with and without
      protein are discussed on the basis of the structural parameters. The last topic
      is on internal dynamics of PCR micelles on timescales from femtoseconds to
      nanoseconds studied by femtosecond time-resolved fluorescence spectroscopy. 

PMID- 24018325
TI  - Enzyme active site interactions by Raman/FTIR, NMR, and ab initio calculations.
AB  - Characterization of enzyme active site structure and interactions at high
      resolution is important for the understanding of the enzyme catalysis.
      Vibrational frequency and NMR chemical shift measurements of enzyme-bound ligands
      are often used for such purpose when X-ray structures are not available or when
      higher resolution active site structures are desired. This review is focused on
      how ab initio calculations may be integrated with vibrational and NMR chemical
      shift measurements to quantitatively determine high-resolution ligand structures
      (up to 0.001 A for bond length and 0.01 A for hydrogen bonding distance) and how
      interaction energies between bound ligand and its surroundings at the active site
      may be determined. Quantitative characterization of substrate ionic states, bond
      polarizations, tautomeric forms, conformational changes and its interactions with
      surroundings in enzyme complexes that mimic ground state or transition state can
      provide snapshots for visualizing the substrate structural evolution along enzyme
      catalyzed reaction pathway. Our results have shown that the integration of
      spectroscopic studies with theoretical computation greatly enhances our ability
      to interpret experimental data and significantly increases the reliability of the
      theoretical analysis.

PMID- 24018327
TI  - Structure and orientation of interfacial proteins determined by sum frequency
      generation vibrational spectroscopy: method and application.
AB  - In situ and real-time characterization of molecular structures and orientation of
      proteins at interfaces is essential to understand the nature of interfacial
      protein interaction. Such work will undoubtedly provide important clues to
      control biointerface in a desired manner. Sum frequency generation vibrational
      spectroscopy (SFG-VS) has been demonstrated to be a powerful technique to study
      the interfacial structures and interactions at the molecular level. This paper
      first systematically introduced the methods for the calculation of the Raman
      polarizability tensor, infrared transition dipole moment, and SFG molecular
      hyperpolarizability tensor elements of proteins/peptides with the secondary
      structures of alpha-helix, 310-helix, antiparallel beta-sheet, and parallel beta
      sheet, as well as the methodology to determine the orientation of interfacial
      protein secondary structures using SFG amide I spectra. After that, recent
      progresses on the determination of protein structure and orientation at different
      interfaces by SFG-VS were then reviewed, which provides a molecular-level
      understanding of the structures and interactions of interfacial proteins,
      specially understanding the nature of driving force behind such interactions.
      Although this review has focused on analysis of amide I spectra, it will be
      expected to offer a basic idea for the spectral analysis of amide III SFG signals
      and other complicated molecular systems such as RNA and DNA. 

PMID- 24018328
TI  - X-ray absorption spectroscopy: a tool to investigate the local structure of metal
      based anticancer compounds in vivo.
AB  - This review gives a brief description of the theory and application of X-ray
      absorption spectroscopy (XAS) comprising both X-ray absorption near-edge
      structure and extended X-ray absorption fine structure, especially focusing onto
      the use in inorganic medicinal chemistry. The advantages and limitations of the
      methods are described and showcased through examples from studies on anticancer
      metal compounds. The strength of XAS and its relevance for the structural
      chemical characterization of metal-based compounds in vivo in native tissue
      samples is exemplified. The common data reduction and analysis strategies are
      presented and recent advances in the field and perspectives for the near future
      are given. 

PMID- 24018329
TI  - Introduction: Biomolecular spectroscopy: advances from integrating experiments
      and theory.

PMID- 24018330
TI  - Multi-class EEG classification of voluntary hand movement directions.
AB  - OBJECTIVE: Studies have shown that low frequency components of brain recordings
      provide information on voluntary hand movement directions. However, non-invasive
      techniques face more challenges compared to invasive techniques. APPROACH: This
      study presents a novel signal processing technique to extract features from non
      invasive electroencephalography (EEG) recordings for classifying voluntary hand
      movement directions. The proposed technique comprises the regularized wavelet
      common spatial pattern algorithm to extract the features, mutual information
      based feature selection, and multi-class classification using the Fisher linear
      discriminant. EEG data from seven healthy human subjects were collected while
      they performed voluntary right hand center-out movement in four orthogonal
      directions. In this study, the movement direction dependent signal-to-noise ratio
      is used as a parameter to denote the effectiveness of each temporal frequency bin
      in the classification of movement directions. MAIN RESULTS: Significant (p <
      0.005) movement direction dependent modulation in the EEG data was identified
      largely towards the end of movement at low frequencies (<=6 Hz) from the midline
      parietal and contralateral motor areas. Experimental results on single trial
      classification of the EEG data collected yielded an average accuracy of (80.24 +/
      9.41)% in discriminating the four different directions using the proposed
      technique on features extracted from low frequency components. SIGNIFICANCE: The
      proposed feature extraction strategy provides very high multi-class
      classification accuracies, and the results are proven to be more statistically
      significant than existing methods. The results obtained suggest the possibility
      of multi-directional movement classification from single-trial EEG recordings
      using the proposed technique in low frequency components.

PMID- 24018331
TI  - Dynamic behavioral strategies during sonar signal emission in roundleaf bats.
AB  - For echolocating bats which emit biosonar pulses nasally, their nostrils are
      surrounded by fleshy appendages that diffract the outgoing ultrasonic waves. The
      posterior leaf, as a prominent part of the noseleaf, was mentioned in previous
      preliminary observations to move during flight in some species of bats, yet the
      detailed motion patterns and thus the possible functional role of the posterior
      leaf movement in biosonar systems remain unclear. In the current work, the motion
      of the posterior leaf of living pratt's roundleaf bats has been investigated
      quantitatively. Temporal characterizations of the noseleaf movement and the
      ultrasonic pulse emission were performed by virtue of synchronized laser
      vibrometry and sound recording. The results showed that the posterior leaf tilted
      forwards and restored to original position within tens of milliseconds. Noseleaf
      motions were temporally correlated with the emitted ultrasonic pulses. The
      surfaces of the posterior leaf were moving in the anterior direction in most of
      the pulse duration. The bats were able to switch the motions on or off. From the
      comparison with the previously reported noseleaf dynamics in horseshoe bat, we
      find similar ratio sizes and displacements of the noseleaves compared to the used
      wavelengths, implying that similar behavioral strategies are utilized by species
      of bats and it may be applied to different components of the signal emitting
      apparatus. It suggests that the dynamic sensing principles may widely play a role
      in the biosonar systems and the investigation on time-variant mechanisms is of
      capital importance to understand the biosonar sensing strategies used by
      echolocating bats. 

PMID- 24018332
TI  - High oxygen consumption rates and scale loss indicate elevated aggressive
      behaviour at low rearing density, while elevated brain serotonergic activity
      suggests chronic stress at high rearing densities in farmed rainbow trout.
AB  - The effect of stocking density on indicators of welfare has been investigated by
      several studies on farmed rainbow trout Oncorhynchus mykiss. However, the
      densities at which welfare are compromised remain ambiguous. Here three different
      stocking density treatments were selected based on the results of a previous
      study, where levels of crowding where determined using the spatial distribution
      of fish in two-tank systems. An un-crowded low density of 25 kgm(-3), the highest
      density accepted by the fish without showing indications of crowding stress of 80
      kgm(-3) as the intermediate density, and the highest density accepted by the fish
      showing indications of crowding stress of 140 kgm(-3) as the high density were
      investigated. The aim of the present study was to examine the effect of being
      held at these densities on indicators of welfare. This was achieved through
      oxygen consumption measurements using automated respirometry, recording fin
      erosion, determining scale loss and analysing plasma cortisol and brain
      serotonergic activity levels. The results obtained in the present study indicated
      that at the lowest density the fish had the space and opportunity to display
      their natural aggressive behaviour and that the fish held at the highest density
      were exposed to a situation of confinement.

PMID- 24018333
TI  - Balancing of specific nutrients and subsequent growth and body composition in the
      slug Arion lusitanicus.
AB  - Feeding generalists typically occupy broad ecological niches and so are
      potentially pre-adapted to a range of novel food objects. In northern Europe, the
      slug Arion lusitanicus has spread rapidly as an invasive species and a serious
      horticultural and agricultural pest. We used nutritional geometry to analyze
      nutrient balancing capabilities and consequences for performance in A.
      lusitanicus when provided with one of three nutritionally fixed diets or when
      given dietary choice. The slugs over-ingested high amounts of the most abundant
      nutrient in order to get more of the limited nutrient. However, they regulated
      protein intake more tightly than carbohydrate intake resulting in a very high
      food intake when fed a protein-poor diet. Growth and body composition were highly
      affected by the nutrient balance of their diet. When given the choice to feed
      from two nutritionally different diets, the slugs selected an intake balance of
      protein and carbohydrate with sufficient precision to maximize growth. Nutrient
      utilization efficiency increased with increasing deficiency of the specific
      nutrient in the diet. Ingested carbohydrate was more efficiently stored as lipid
      in slugs fed more carbohydrate-poor diets, and ingested nitrogen was more
      efficiently incorporated into slug bodies in slugs fed more protein-poor diets.
      Our experiments suggest that the evolved behavioral and physiological regulatory
      capacities of A. lusitanicus may explain some of the success that this slug
      experiences as an invasive species. We furthermore propose that invasive species
      might be more dependent on high protein availability in the environment than non
      invasive species. 

PMID- 24018335
TI  - Bad news for neuroprotective therapies in PD?

PMID- 24018334
TI  - Convergence of innate immunity and insulin resistance as evidenced by increased
      nucleotide oligomerization domain (NOD) expression and signaling in monocytes
      from patients with type 2 diabetes.
AB  - Despite the well known role of nucleotide oligomerization domain (NOD) receptor
      proteins in innate immunity, their association with diabetes is less explored.
      Here we report the transcriptional level of NODs and their downstream molecular
      signatures in CD14(+) monocytes from subjects with different grades of glucose
      tolerance. NOD1 and NOD2 mRNA expression were significantly up-regulated in
      monocytes from patients with type 2 diabetes (T2DM) and positively correlated
      with HOMA-IR and poor glycemic control. Patients with T2DM also exhibited
      increased monocyte activation markers (CD11b and CD36) and proinflammatory
      signals downstream of NOD (RIPK2 and NFkappaB) along with the increased
      circulatory levels of TNF-alpha and IL-6. In vitro stimulation of monocytes with
      NOD specific ligands-i-EDAP and MDP significantly up regulated the mRNA
      expression of NOD1 and NOD2 respectively in T2DM. Our study exposes up regulation
      of NODs in monocytes as an important component of inflammation and insulin
      resistance in patients with T2DM. 

PMID- 24018336
TI  - Linked clinical trials--the development of new clinical learning studies in
      Parkinson's disease using screening of multiple prospective new treatments.
AB  - Finding new therapies for Parkinson's disease (PD) is a slow process. We
      assembled an international committee of experts to examine drugs potentially
      suitable for repurposing to modify PD progression. This committee evaluated
      multiple drugs currently used, or being developed, in other therapeutic areas, as
      well as considering several natural, non-pharmaceutical compounds. The committee
      prioritized which of these putative treatments were most suited to move
      immediately into pilot clinical trials. Aspects considered included known modes
      of action, safety, blood-brain-barrier penetration, preclinical data in animal
      models of PD and the possibility to monitor target engagement in the brain. Of
      the 26 potential interventions, 10 were considered worth moving forward into
      small, parallel 'learning' clinical trials in PD patients. These trials could be
      funded in a multitude of ways through support from industry, research grants and
      directed philanthropic donations. The committee-based approach to select the
      candidate compounds might help rapidly identify new potential PD treatment
      strategies for use in clinical trials. 

PMID- 24018337
TI  - A qualitative study of preadolescent boys' and girls' body image: gendered ideals
      and sociocultural influences.
AB  - This qualitative study examined preadolescent boys' and girls' body ideals, and
      peer and media factors that shape these ideals. Sixty-eight children aged 8-10
      participated in semi-structured interviews: 19 boys and 17 girls in individual
      interviews and 16 boys and 16 girls in eight group interviews. Techniques from
      grounded theory were used to analyze the data. Findings demonstrated that fitness
      was an important element of boys' and girls' body ideals. For boys the emphasis
      was on sport, and this was promoted by their peer interactions and the sportsmen
      they admired. For girls the focus was on looking good, and this was reinforced by
      their peer conversations, and the actresses and singers they admired. Focus
      groups further highlighted how peers both reinforced media messages, yet also
      helped children critique media messages. Implications are discussed for
      prevention programs that need to be specifically tailored for boys and girls. 

PMID- 24018338
TI  - Empowerment, feminism, and self-efficacy: relationships to body image and
      disordered eating.
AB  - Sociocultural norms pertaining to an ideal of thinness for women likely play a
      role in the development and maintenance of disturbance in body image, and by
      extension, disordered eating. However, competing norms associated with feminism
      may buffer women from pressures associated with achieving the thin ideal. The
      present study explored the relationship between feminist ideology, empowerment,
      and self-efficacy relative to body image and eating behavior with a sample of
      U.S. undergraduate women (N=318) attending a southeastern U.S. mid-sized
      university. In planned hierarchical multiple regression analyses, endorsement of
      feminist ideology predicted perceptions of positive body image, but did not
      appear to predict disordered eating. Self-efficacy emerged as a robust predictor
      of positive body image and lower disordered eating even after controlling for
      perceptions of personal empowerment and feminism. Results, although limited by
      correlational data, suggest that self-efficacy may protect college-aged women
      from disordered eating and negative body image. 

PMID- 24018339
TI  - The clinical status of cartilage tissue regeneration in humans.
AB  - PURPOSE: To provide a comprehensive overview of the basic science and clinical
      evidence behind cartilage regeneration techniques as they relate to surgical
      management of chondral lesions in humans. METHODS: A descriptive review of
      current literature. RESULTS: Articular cartilage defects are common in orthopedic
      practice, with current treatments yielding acceptable short-term but inconsistent
      long-term results. Tissue engineering techniques are being employed with aims of
      repopulating a cartilage defect with hyaline cartilage containing living
      chondrocytes with hopes of improving clinical outcomes. Cartilage tissue
      engineering broadly involves the use of three components: cell source,
      biomaterial/membranes, and/or growth stimulators, either alone or in any
      combination. Tissue engineering principles are currently being applied to
      clinical medicine in the form of autologous chondrocyte implantation (ACI) or
      similar techniques. Despite refinements in technique, current literature fails to
      support a clinical benefit of ACI over older techniques such as microfracture
      except perhaps for larger (>4 cm) lesions. Modern ACI techniques may be
      associated with lower operative revision rates. The notion that ACI-like
      procedures produce hyaline-like cartilage in humans remains unsupported by high
      quality clinical research. CONCLUSIONS: Many of the advancements in tissue
      engineering have yet to be applied in a clinical setting. While basic science has
      refined orthopedic management of chondral lesions, available evidence does not
      conclude the superiority of modern tissue engineering methods over other
      techniques in improving clinical symptoms or restoring native joint mechanics. It
      is hoped further research will optimize ease of cell harvest and growth, enhanced
      cartilage production, and improve cost-effectiveness of medical intervention.

PMID- 24018340
TI  - A liquid chromatography/mass spectrometry-based generic detection method for
      biochemical assay and hit discovery of histone methyltransferases.
AB  - Epigenetic modifications of the genome, such as DNA methylation and
      posttranslational modifications of histone proteins, contribute to gene
      regulation. Growing evidence suggests that histone methyltransferases are
      associated with the development of various human diseases, including cancer, and
      are promising drug targets. High-quality generic assays will facilitate drug
      discovery efforts in this area. In this article, we present a liquid
      chromatography/mass spectrometry (LC/MS)-based S-adenosyl homocysteine (SAH)
      detection assay for histone methyltransferases (HMTs) and its applications in HMT
      drug discovery, including analyzing the activity of newly produced enzymes,
      developing and optimizing assays, performing focused compound library screens and
      orthogonal assays for hit confirmations, selectivity profiling against a panel of
      HMTs, and studying mode of action of select hits. This LC/MS-based generic assay
      has become a critical platform for our methyltransferase drug discovery efforts. 

PMID- 24018341
TI  - Preservation of mitochondrial functional integrity in mitochondria isolated from
      small cryopreserved mouse brain areas.
AB  - Studies of mitochondrial bioenergetics in brain pathophysiology are often
      precluded by the need to isolate mitochondria immediately after tissue dissection
      from a large number of brain biopsies for comparative studies. Here we present a
      procedure of cryopreservation of small brain areas from which mitochondrial
      enriched fractions (crude mitochondria) with high oxidative phosphorylation
      efficiency can be isolated. Small mouse brain areas were frozen and stored in a
      solution containing glycerol as cryoprotectant. Crude mitochondria were isolated
      by differential centrifugation from both cryopreserved and freshly explanted
      brain samples and were compared with respect to their ability to generate
      membrane potential and produce ATP. Intactness of outer and inner mitochondrial
      membranes was verified by polarographic ascorbate and cytochrome c tests and
      spectrophotometric assay of citrate synthase activity. Preservation of structural
      integrity and oxidative phosphorylation efficiency was successfully obtained in
      crude mitochondria isolated from different areas of cryopreserved mouse brain
      samples. Long-term cryopreservation of small brain areas from which intact and
      phosphorylating mitochondria can be isolated for the study of mitochondrial
      bioenergetics will significantly expand the study of mitochondrial defects in
      neurological pathologies, allowing large comparative studies and favoring
      interlaboratory and interdisciplinary analyses. 

PMID- 24018342
TI  - Measuring quality of care: considering conceptual approaches to quality indicator
      development and evaluation.
AB  - OBJECTIVE: In this article, we describe one approach for developing and
      evaluating quality indicators. STUDY DESIGN AND SETTING: We focus on describing
      different conceptual approaches to quality indicator development, review one
      approach for developing quality indicators, outline how to evaluate quality
      indicators once developed, and discuss quality indicator maintenance. RESULTS:
      The key steps for developing quality indicators include specifying a clear goal
      for the indicators; using methodologies to incorporate evidence, expertise, and
      patient perspectives; and considering contextual factors and logistics of
      implementation. The Strategic Framework Board and the National Quality Measure
      Clearinghouse have developed criteria for evaluating quality indicators that
      complement traditional psychometric evaluations. Optimal strategies for quality
      indicator maintenance and dissemination have not been determined, but experiences
      with clinical guideline maintenance may be informative. CONCLUSION: For quality
      indicators to effectively guide quality improvement efforts, they must be
      developed, evaluated, maintained, and implemented using rigorous evidence
      informed practices.

PMID- 24018343
TI  - Diagnostic probability function for acute coronary heart disease garnered from
      experts' tacit knowledge.
AB  - OBJECTIVES: Knowing about a diagnostic probability requires general knowledge
      about the way in which the probability depends on the diagnostic indicators
      involved in the specification of the case at issue. Diagnostic probability
      functions (DPFs) are generally unavailable at present. Our objective was to
      illustrate how diagnostic experts' case-specific tacit knowledge about diagnostic
      probabilities could be garnered in the form of DPFs. STUDY DESIGN AND SETTING:
      Focusing on diagnosis of acute coronary heart disease (ACHD), we presented
      doctors with extensive experience in hospitals' emergency departments a set of
      hypothetical cases specified in terms of an inclusive set of diagnostic
      indicators. We translated the medians of these experts' case-specific
      probabilities into a logistic DPF for ACHD. RESULTS: The principal result was the
      experts' typical diagnostic probability for ACHD as a joint function of the set
      of diagnostic indicators. A related result of note was the finding that the
      experts' probabilities in any given case had a surprising degree of variability.
      CONCLUSION: Garnering diagnostic experts' case-specific tacit knowledge about
      diagnostic probabilities in the form of DPFs is feasible to accomplish. Thus,
      once the methodology of this type of work has been "perfected," practice-guiding
      diagnostic expert systems can be developed.

PMID- 24018344
TI  - Measuring quality of care: considering measurement frameworks and needs
      assessment to guide quality indicator development.
AB  - OBJECTIVE: In this article, we describe one approach for evaluating the value of
      developing quality indicators (QIs). STUDY DESIGN AND SETTING: We focus on
      describing how to develop a conceptual measurement framework and how to evaluate
      the need to develop QIs. A recent process to develop QIs for injury care is used
      for illustration. RESULTS: Key steps to perform before developing QIs include
      creating a conceptual measurement framework, determining stakeholder
      perspectives, and performing a QI needs assessment. QI development is likely to
      be most beneficial for medical problems for which quality measures have not been
      previously developed or are inadequate and that have a large burden of illness to
      justify quality measurement and improvement efforts, are characterized by
      variable or substandard care such that opportunities for improvement exist, and
      have evidence that improving quality of care will improve patient health.
      CONCLUSION: By developing a conceptual measurement framework and performing a QI
      needs assessment, developers and users of QIs can target their efforts.

PMID- 24018345
TI  - Reporting quality of survival analyses in medical journals still needs
      improvement. A minimal requirements proposal.
AB  - OBJECTIVES: We reviewed publications with two main objectives: to describe how
      survival analyses are reported across medical journal specialties and to evaluate
      changes in reporting across periods and journal specialties. STUDY DESIGN AND
      SETTING: Systematic review of clinical research articles published in 1991 and
      2007, in 13 high-impact medical journals. RESULTS: The number of articles
      performing survival analysis published in 1991 (104) and 2007 (240) doubled (17%
      vs. 33.5%; P = 0.000), although not uniformly across specialties. The percentage
      of studies using regression models and the number of patients included also
      increased. The presentation of results improved, although only the reporting of
      precision of effect estimates reached satisfactory levels (53.1% in 1991 vs.
      94.2% in 2007; P = 0.000). Quality of reporting also varied across specialties;
      for example, cardiology articles were less likely than oncology ones to discuss
      sample size estimation (odds ratio = 0.12; 95% confidence interval: 0.05, 0.30).
      We also detected an interaction effect between period and specialty regarding the
      likelihood of reporting precision of curves and precision of effect estimates.
      CONCLUSION: The application of survival analysis to medical research data is
      increasing, whereas improvement in reporting quality is slow. We propose a list
      of minimum requirements for improved application and description of survival
      analysis.

PMID- 24018346
TI  - Quality indicators and performance measures: methods for development need more
      standardization.

PMID- 24018347
TI  - Quality scores do not predict discrepant statistical significances among meta
      analyses on different targets of glycemic control in type 2 diabetes.
AB  - OBJECTIVES: To examine differences in conclusions, statistical significances, and
      quality of systematic reviews on preventive effects of different targets of blood
      glucose lowering on macrovascular events in patients with type 2 diabetes. STUDY
      DESIGN AND SETTING: We searched MEDLINE, the Cochrane Database of Systematic
      Reviews, and Embase until October 15, 2011. Systematic reviews using meta
      analyses to compare macrovascular events in patients with type 2 diabetes
      randomized to different therapeutic targets of blood glucose were eligible for
      inclusion in this study. Effect measures were extracted and quality was assessed
      by Overview Quality Assessment Questionnaire, Assessment of Multiple Systematic
      Reviews, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
      An additional checklist was used to control for completeness and suitability of
      included trials, correctness of data extraction, and choice of outcome
      parameters. RESULTS: The 16 included systematic reviews were partially discrepant
      in statistical significances of reported outcome parameters. Twelve systematic
      reviews did not include available relevant trials and included eight systematic
      reviews that should not have been included according to the systematic review's
      aim and search strategies. Quality differed considerably among systematic
      reviews. CONCLUSION: Physicians, researchers, and policy makers should bear in
      mind that common quality assessment instruments are necessary but not sufficient
      to guarantee reliable results and conclusions obtained from meta-analyses.

PMID- 24018348
TI  - No evidence for intervention-dependent influence of methodological features on
      treatment effect.
AB  - OBJECTIVES: The goal of this systematic review was to evaluate if the influence
      of methodological features on treatment effect differs between types of
      intervention. STUDY DESIGN AND SETTING: MEDLINE, Embase, Web of Science, Cochrane
      methodology register, and reference lists were searched for meta-epidemiologic
      studies on the influence of methodological features on treatment effect. Studies
      analyzing influence of methodological features related to internal validity were
      included. We made a distinction among surgical, pharmaceutical, and therapeutical
      as separate types of intervention. Heterogeneity was calculated to identify
      differences among these types. RESULTS: Fourteen meta-epidemiologic studies were
      found with 51 estimates of influence of methodological features on treatment
      effect. Heterogeneity was observed among the intervention types for
      randomization. Surgical intervention studies showed a larger treatment effect
      when randomized; this was in contrast to pharmaceutical studies that found the
      opposite. For allocation concealment and double blinding, the influence of
      methodological features on the treatment effect was comparable across different
      types of intervention. For the remaining methodological features, there were
      insufficient observations. CONCLUSION: The influence of allocation concealment
      and double blinding on the treatment effect is consistent across studies of
      different interventional types. The influence of randomization although, may be
      different between surgical and nonsurgical studies.

PMID- 24018349
TI  - Short-term lower-body plyometric training improves whole body BMC, bone metabolic
      markers, and physical fitness in early pubertal male basketball players.
AB  - The effects of a 9-week lower-body plyometric training program on bone mass, bone
      markers and physical fitness was examined in 51 early pubertal male basketball
      players divided randomly into a plyometric group (PG: 25 participants) and a
      control group (CG: 26 participants). Areal bone mineral density (aBMD), bone
      mineral content (BMC), and bone area (BA) in the whole body, L2-L4 vertebrae, and
      in total hip, serum levels of osteocalcin (Oc) and C-terminal telopeptide
      fragment of Type I collagen (CTx), jump, sprint and power abilities were assessed
      at baseline and 9 weeks. Group comparisons were done by independent student's t
      test between means and analyses of (ANOVA) and covariance (ANCOVA), adjusting for
      baseline values. PG experienced a significant increase in Oc (p < .01) and all
      physical fitness except for the 5-jump test. However, there was no improvement in
      aBMD, BMC and BA in any measured site, except in whole body BMC of the PG. A
      positive correlation was observed between percentage increase (Delta%) of
      physical fitness and those of (Oc) for the PG. In summary, biweekly sessions of
      lower body plyometric training program were successful for improving whole body
      BMC, bone formation marker (Oc) and physical fitness in early pubertal male
      basketball players. 

PMID- 24018350
TI  - "Model" patients and the consequences of provider responses to vaccine hesitancy.
AB  - The manner in which providers respond to parental concerns about the recommended
      childhood vaccination schedule is an area of increasing interest in pediatrics
      and medical ethics. Like many aspects of vaccination policy and practice,
      evaluating the reactions of providers to parental vaccine hesitancy--including
      the potential dismissal of such families from their practices--requires an
      appreciation of the twin character of vaccination as both a public health program
      as well as an individual preventive intervention. Accordingly, the ethics of
      vaccination combine many aspects of traditional medical ethics, such as respect
      for patient autonomy, the primacy of informed consent, and concern for the doctor
      patient relationship, with the relatively newer discourse of public health
      ethics, one that directs particular attention to the health of populations and
      the pursuit of social justice. When parents are hesitant about vaccination for
      their children, providers may face a significant challenge reconciling their
      commitment to the health of those children, their respect for the perspectives of
      parents, and their interest in the health of their other patients and their
      communities. The tensions and potential conflicts among these considerations help
      to explain why provider responses to vaccine hesitancy have emerged as a frequent
      topic of discussion among practitioners, public health advocates, and ethicists
      alike.

PMID- 24018351
TI  - A randomised, controlled trial comparing the long-term effects of peripherally
      inserted central catheter placement in chemotherapy patients using B-mode
      ultrasound with modified Seldinger technique versus blind puncture.
AB  - OBJECTIVE: To compare the effects of peripherally inserted central venous
      catheter (PICC) placement using B-mode ultrasound with the modified Seldinger
      technique (BUMST) versus the blind puncture. METHODS: One hundred chemotherapy
      patients were recruited to participate in a randomised, controlled trial in
      Guangzhou, China. Fifty were assigned to the experimental group (using BUMST),
      and 50 were assigned to the control group (blind puncture). Demographic and
      background data, data related to PICC placement, complications after PICC
      placement, the patients' degree of comfort (determined via a questionnaire), and
      patients' costs for PICC maintenance were collected to compare the effects of the
      two methods. T-tests and chi-square tests were used to analyse the data; p < 0.05
      was accepted as statistically significant. RESULTS: Nighty-eight of the 100 PICCs
      were successfully inserted (50 in the experimental group and 48 in the control
      group). Compared with the control group, the experimental group had a lower rate
      of unplanned catheter removal (4.0% vs. 18.7%; p = 0.02), a lower incidence of
      mechanical phlebitis (0% vs. 22.9%; p < 0.001), a lower incidence of venous
      thrombosis (0% vs. 8.3%; p = 0.037), and a higher incidence of catheter migration
      (32% vs. 2.1%; p < 0.001). Compared with the control group, the experimental
      group experienced significantly less severe contact dermatitis (p = 0.038), had
      improved comfort at 1 week, 1 month, 2 months, and 3 months after PICC placement
      (p < 0.001), and had lower costs for PICC maintenance at 2 months, 3 months and
      when the catheter was removed (p < 0.05). CONCLUSIONS: Using B-mode ultrasound
      with MST for PICC placement reduced complications and patients' costs for PICC
      maintenance and improved patients' degree of comfort; thus, this procedure should
      be more widely used. The clinical trial registration number: ChiCTR-TRC-12002749.

PMID- 24018352
TI  - Opposite regulatory effects of IFN-beta and IL-3 on C-type lectin receptors,
      antigen uptake, and phagocytosis in human macrophages.
AB  - CLRs are predominantly expressed in macrophages and myeloid DCs, where they play
      a key role in antigen recognition, scavenging, and host defense against
      pathogens. To identify novel immunoregulatory cytokines and networks involved in
      the control of these functions, we analyzed the coordinate effects of IFN-beta
      and IL-3 on CLR expression, antigen uptake, and phagocytosis in human MDMs and
      MDDCs. We report that these cytokines exert opposite regulatory effects on the
      expression of CLRs and endocytic/phagocytic activities of MDMs. Specifically, IFN
      beta markedly inhibits the expression of MR and Dectin-1 during MDM
      differentiation and impairs the capacity of MDM to internalize antigens and
      phagocytose unopsonized Candida albicans. Conversely, IL-3 up-modulates MR,
      Dectin-1, and DC-SIGN, thus allowing more efficient uptake/phagocytosis.
      Interestingly, IL-3 counteracts the IFN-beta effect on antigen uptake/processing
      by fully restoring MR expression in IFN-beta-primed MDMs. In contrast, the
      phagocytic activity is only partially restored as a result of the failure of IL-3
      in counteracting IFN-beta-induced Dectin-1 suppression. Notably, IFN-beta
      mediated impairment of CLR expression/function occurs in macrophages but not in
      MDDCs. These results identify IFN-beta and IL-3 as unrecognized regulators of CLR
      expression and function, unraveling a novel interaction between these cytokines
      instrumental for the regulation of the macrophage response to pathogens. 

PMID- 24018353
TI  - Gfi-1 is the transcriptional repressor of SOCS1 in acute myeloid leukemia cells.
AB  - Silencing of SOCS1, a TSG, has been detected in various malignancies, including
      AML. However, the underlying mechanism of SOCS1 inactivation remains elusive. In
      this study, we explored the role of histone methylation in SOCS1 expression in
      AML cells. By ChIP assay, we demonstrated that G9a and SUV39H1, two enzymes
      catalyzing H3K9 methylation, were physically associated with the SOCS1 promoter,
      and treatment with chaetocin, a histone methyltransferase inhibitor, suppressed
      H3K9 methylation on the SOCS1 promoter and enhanced SOCS1 expression.
      Furthermore, knockdown of G9a and SUV39H1 by siRNA could also induce SOCS1
      expression. On the other hand, SOCS1 knockdown by shRNA eliminated chaetocin
      induced cell apoptosis. To investigate further whether any transcription factor
      was involved in H3K9 methylation-related SOCS1 repression, we scanned the
      sequences of the SOCS1 gene promoter and found two binding sites for Gfi-1, a
      transcription repressor. By DNA pull-down and ChIP assays, we showed that Gfi-1
      directly bound the SOCS1 promoter, and ectopic Gfi-1 expression suppressed STAT5
      induced SOCS1 promoter activation. In contrast, Gfi-1 knockdown by shRNA enhanced
      SOCS1 expression and inhibited STAT5 expression. Moreover, the knockdown of G9a
      completely rescued the repressive effect of Gfi-1 on STAT5A-induced SOCS1
      promoter activation. Collectively, our study indicates that the expression of Gfi
      1 contributes to SOCS1 silencing in AML cells through epigenetic modification,
      and suppression of histone methyltransferase can provide new insight in AML
      therapy. 

PMID- 24018354
TI  - Toll-like receptor 2/4 links to free fatty acid-induced inflammation and beta
      cell dysfunction.
AB  - T2D is a metabolic and inflammatory disease characterized by deteriorating beta
      cell function and increased levels of inflammatory cytokines. Low-grade
      inflammation and innate immune system activation lead to beta-cell failure.
      Recently, SFAs have been proposed as triggers of metabolism-associated
      inflammation through the TLR family of PRRs. In this review, recent progress in
      defining the molecular basis of FFA-associated TLR2/4 activation and signaling in
      beta-cell dysfunction and apoptosis is summarized. Furthermore, we highlight
      links between TLRs and diabetic complications, insulin resistance, and autophagy.
      This knowledge may facilitate novel strategies to abrogate inflammation in T2D. 

PMID- 24018355
TI  - Pectus excavatum in children with laryngomalacia.
AB  - BACKGROUND: Laryngomalacia is the most common congenital laryngeal anomaly and is
      associated with several disorders including gastric reflux, sleep apnea,
      hypotonia and failure to thrive. Pectus excavatum (PE) is the most common chest
      wall deformity affecting 1-300/1000 individuals. Though many authors presume a
      relationship between PE and laryngomalacia, there is no published data to
      establish this association. GOAL: To test the hypothesis that patients referred
      to our pediatric otolaryngology clinic for evaluation of laryngomalacia exhibit
      higher rates of PE than the general population. METHODS: Retrospective review of
      prospectively enrolled children who presented with laryngomalacia (January 2008
      June 2012) to a tertiary care, hospital based, pediatric otolaryngology practice.
      Each chart was examined for a concurrent diagnosis of pectus deformity. RESULTS:
      Of the 137 laryngomalacia patients, 9 (6.6%) had documented PE. This represents a
      significantly increased rate of PE when compared to children without
      laryngomalacia (p = 0.001). Four of the 9 children with PE underwent
      supraglottoplasty for laryngomalacia, a significantly greater proportion than the
      9/128 of the children with isolated laryngomalacia who underwent
      supraglottoplasty (p = 0.004). CONCLUSIONS: This study suggests an association
      between laryngomalacia and PE. Pediatric otolaryngologists should be cognizant of
      this relationship, though further studies are needed to elucidate the nature of
      this association.

PMID- 24018356
TI  - Critical thinking skills of undergraduate nursing students: description and
      demographic predictors.
AB  - AIM: This study investigated the critical thinking skills among undergraduate
      nursing students in Australia to obtain a profile and determine demographic
      predictors of critical thinking. BACKGROUND: There is universal agreement that
      being a critical thinker is an outcome requirement for many accreditation and
      registering nursing bodies. Most studies provide descriptive statistical
      information about critical thinking skills while some have studied the changes in
      critical thinking after an intervention. Limited research about factors that
      predict critical thinking skills is available. METHODS: A cross-sectional
      descriptive study was conducted using convenience sampling. Two hundred and sixty
      nine students were recruited across three years of an undergraduate programme in
      2009. Most students' age ranged from under 20 to 34 years (58%), 87% were female,
      91% were Australian and 23% of first and second year students had nursing
      associated experience external to the university. Data about critical thinking
      skills were collected via the Health Science Reasoning Test (HSRT). Linear
      regression analysis investigated the predictors of nursing students' critical
      thinking skills. RESULTS: The students in third year had a profile of critical
      thinking skills comparable with HSRT norms. Year of study predicted higher
      critical thinking scores for all domains (p<0.001) except the subscale, analysis.
      Nationality predicted higher scores for total CT skill scores (p<0.001) and
      subscales, inductive (p=0.001) and deductive reasoning (p=0.001). Nursing
      associated experience predicted higher scores for the subscale, analysis
      (p<0.001). Age and gender were not predictive. However, these demographic
      predictors only accounted for a small variance obtained for the domains of CT
      skills. CONCLUSION: An understanding of factors that predict nursing students' CT
      skills is required. Despite this study finding a number of significant predictors
      of nursing students' CT skills, there are others yet to be understood. Future
      research is recommended exploring explicit CT instructional approaches and
      nursing students' CT skills.

PMID- 24018357
TI  - Strengthening Nursing Education in Three Southeast Asian Countries Program
      (SNESEA): a model for addressing the nursing shortage on a regional level.

PMID- 24018358
TI  - Self-assessed level of competence of graduating nursing students and factors
      related to it.
AB  - BACKGROUND: The transition from a nursing student to a professional nurse is both
      challenging and stressful. Competence of graduating nursing students is related
      to patient safety and there is a need for assessment of competence. However,
      there is a lack of research on the level of competence at the moment of
      graduation. OBJECTIVES: To describe the level of competence of graduating nursing
      students based on students' self-assessments and to identify possible related
      factors. DESIGN: Cross-sectional survey design. METHODS: The data were collected
      using an on-line survey (the Nurse Competence Scale) in 2011 and administered to
      302 graduating nursing students in Finland practicing in their final clinical
      placement in university hospitals. The sample contained 154 students (response
      rate 51%). The data were analyzed statistically. RESULTS: The self-assessed
      overall competence was on good level (66.7, VAS 0-100). The competence was
      highest in helping role and in diagnostic functions, being slightly lower in
      therapeutic interventions and work role. Pedagogical atmosphere during the final
      clinical placement had a statistically significantly positive correlation with
      the overall level of competence. CONCLUSIONS: Graduating nursing students have
      good competence at the moment of graduation based on their self-assessments. Self
      assessment is a basis for competence development, and systematic self-assessments
      should be used during the education. Teacher and supervisor assessments and
      knowledge-tests could be used alongside with self-assessments of competence to
      give a wider picture of the competence.

PMID- 24018359
TI  - Empowering the registered nurses of tomorrow: students' perspectives of a
      simulation experience for recognising and managing a deteriorating patient.
AB  - BACKGROUND: Recognising and responding to patients who are deteriorating are key
      aspects to improving outcomes. Simulations provide students with exposure to
      deteriorating patient scenarios and the role of nurses in such events. The number
      of programmes seeking to provide best possible simulation experiences is growing
      exponentially. Robust evaluation of these experiences is crucial to ensure
      maximum benefit. OBJECTIVES: To assess the impact of a deteriorating patient
      simulation experience on students' technical and communication skills; and to
      determine if differing study programmes and years of previous nursing experience
      influenced students' responses and experiences. METHODS: A convenience sample of
      final year nursing students (N=57) in a medical-surgical course at a large urban
      university completed a descriptive pre/post simulation survey rating their
      technical skills and communication abilities in recognising and responding to
      patient deterioration. Changes in pre/post scores were analysed including
      influence of study programme (3-year, 2-year Enrolled Nurse, 2-year Graduate
      Entry); gender; and years nursing experience (beyond course clinical practicum).
      RESULTS: Statistically significant improvements in post-simulation survey scores
      were demonstrated for combined student group data. Students with greater years of
      nursing experience had statistically higher scores than those with less
      experience in both pre- and post-surveys. Specific improvements were identified
      for: assessing a deteriorating patient; and in seeking help from the medical
      officer or external service. CONCLUSIONS: All student groups gained benefit in
      participating in a deteriorating patient simulation. For this group, greater
      years of prior nursing experience led to higher pre- and post-survey scores. The
      learning activity provided students an experience of the importance of
      recognising and responding to an acute situation in a timely manner which may be
      recalled in subsequent clinical situations.

PMID- 24018360
TI  - Differential metalloprotease content and activity of three Loxosceles spider
      venoms revealed using two-dimensional electrophoresis approaches.
AB  - Loxosceles bites have been associated with characteristic dermonecrotic lesions
      with gravitational spreading and systemic manifestations. Venom primarily
      comprises peptides and protein molecules (5-40 kDa) with multiple biological
      activities. Although poorly studied, metalloproteases have been identified in
      venoms of several Loxosceles species, presenting proteolytic effects on
      extracellular matrix components. The characterization of an Astacin-like protease
      (LALP) in Loxosceles intermedia venom was the first report of an Astacin family
      member as a component of animal venom. Recently, these proteases were described
      as a gene family in L. intermedia, Loxosceles laeta and Loxosceles gaucho.
      Herein, the whole venom complexity of these three Loxosceles species was analyzed
      using two-dimensional electrophoresis (2DE). Subproteomes of LALPs were explored
      through 2DE immunostaining using anti-LALP1 antibodies and 2DE gelatin zymogram.
      Proteins presented molecular masses ranging from 24 to 29 kDa and the majority of
      these molecules had basic or neutral isoelectric points (6.89-9.93). Likewise,
      the measurement of gelatinolytic effects of Loxosceles venom using fluorescein
      gelatin showed that the three venoms have distinct proteolytic activities. The
      metalloprotease fibrinogenolytic activities were also evaluated. All venoms
      showed fibrinogenolytic activity with different proteolytic effects on Aalpha and
      Bbeta chains of fibrinogen. The results reported herein suggest that the LALP
      family is larger than indicated in previously published data and that the complex
      profile of the gelatinolytic activity reflects their relevance in loxoscelism.
      Furthermore, our investigation implicates the brown spider venom as a source of
      Astacin-like proteases for use in loxoscelism studies, cell biology research and
      biotechnological applications. 

PMID- 24018361
TI  - Differential tolerance to cyanobacterial exposure between geographically distinct
      populations of Perca fluviatilis.
AB  - Toxic cyanobacterial blooms are an important problem worldwide. Cyanobacteria may
      negatively impact young-of-the-year (YOY) fish directly (toxin production,
      turbidity, decrease in water quality) or indirectly (trophic toxin transfer,
      changes in prey species composition). Here we test whether there are any
      differences in cyanobacterial tolerance between four geographically distinct
      populations of European perch (Perca fluviatilis). We show that P. fluviatilis
      may develop tolerance against cyanobacteria demonstrated by the ability of
      individuals from a marine site (exposed to annual cyanobacterial blooms) to
      increase their detoxification more than individuals from an oligotrophic site
      (rarely exposed to cyanobacteria). Our results also revealed significant
      interaction effects between genotypes within a population and response to
      cyanobacterial exposure in terms of absolute growth and detoxification activity.
      This genotype by treatment interaction may result in local adaptations to
      cyanobacterial exposure in P. fluviatilis. Hence, the sensitivity against
      cyanobacterial exposure may differ between within species populations increasing
      the importance of local management of fish populations. 

PMID- 24018364
TI  - Kinect Xbox 360 as a therapeutic modality for children with cerebral palsy in a
      school environment: a preliminary study.
AB  - BACKGROUND: Limited evidence is available about the effectiveness of virtual
      reality using low cost commercial consoles for children with developmental delay.
      OBJECTIVE: The aim of this preliminary study is to evaluate the usefulness of a
      videogame system based on non-immersive virtual reality technology (Xbox 360
      KinectTM) to support conventional rehabilitation treatment of children with
      cerebral palsy. Secondarily, to objectify changes in psychomotor status of
      children with cerebral palsy after receiving rehabilitation treatment in addition
      with this last generation game console. METHODS: 11 children with cerebral palsy
      were included the study. A baseline, a post-treatment and a follow-up assessment
      were performed related to motor and the process skills, balance, gait speed,
      running and jumping and fine and manual finger dexterity. All the participants
      completed 8 weeks of videogame treatment, added to their conventional
      physiotherapy treatment, with Xbox 360 KinectTM (Microsoft) game console.
      RESULTS: The Friedman test showed significant differences among the three
      assessments for each variable: GMFM (p = 0.001), AMPS motor (p = 0.001), AMPS
      process (p = 0.010), PRT (p = 0.005) and 10 MW (p = 0.029). Wilcoxon test showed
      significant statistically differences pre and post-treatment, in all the values.
      Similarly, results revealed significant differences between basal and follow-up
      assessment. There were not statistical differences between post-treatment and
      follow-up evaluation, indicating a long-term maintenance of the improvements
      achieved after treatment. CONCLUSIONS: Low cost video games based on motion
      capture are potential tools in the rehabilitation context in children with CP.
      Our Kinect Xbox 360 protocol has showed improvements in balance and ADL in CP
      participants in a school environment, but further studies are need to validate
      the potential benefits of these video game systems as a supplement for
      rehabilitation of children with CP.

PMID- 24018362
TI  - Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current
      status.
AB  - Since the introduction of Doxil(r) on the market nearly 20years ago, a number of
      nanomedicines have become part of treatment regimens in the clinic. With the
      exception of antibody-drug conjugates, these nanomedicines are all devoid of
      targeting ligands and rely solely on their physicochemical properties and the
      (patho)physiological processes in the body for their biodistribution and
      targeting capability. At the same time, many preclinical studies have reported on
      nanomedicines exposing targeting ligands, or ligand-targeted nanomedicines, yet
      none of these have been approved at this moment. In the present review, we
      provide a concise overview of 13 ligand-targeted particulate nanomedicines
      (ligand-targeted PNMs) that have progressed into clinical trials. The progress of
      each ligand-targeted PNM is discussed based on available (pre)clinical data. Main
      conclusions of these analyses are that (a) ligand-targeted PNMs have proven to be
      safe and efficacious in preclinical models; (b) the vast majority of ligand
      targeted PNMs is generated for the treatment of cancer; (c) contribution of
      targeting ligands to the PNM efficacy is not unambiguously proven; and (d)
      targeting ligands do not cause localization of the PNM within the target tissue,
      but rather provide benefits in terms of target cell internalization and target
      tissue retention once the PNM has arrived at the target site. Increased
      understanding of the in vivo fate and interactions of the ligand-targeted PNMs
      with proteins and cells in the human body is mandatory to rationally advance the
      clinical translation of ligand-targeted PNMs. Future perspectives for ligand
      targeted PNM approaches include the delivery of drugs that are unable or
      inefficient in passing cellular membranes, treatment of drug resistant tumors,
      targeting of the tumor blood supply, the generation of targeted vaccines and
      nanomedicines that are able to cross the blood-brain barrier. 

PMID- 24018365
TI  - The effectiveness of different treatment modalities for the rehabilitation of
      unilateral neglect in stroke patients: a systematic review.
AB  - BACKGROUND: Patients suffering from unilateral neglect syndrome (UNS) are not
      able to respond to stimuli administered to the side of the body opposite to the
      lesion. UNS is most commonly seen after right-hemisphere lesions. Patients with
      UNS experience more problems with activities of daily living and recovery after
      stroke is delayed. OBJECTIVE: To investigate which treatment modalities can
      alleviate the symptoms of UNS after stroke and to determine their effectiveness.
      METHODS: Databases PubMed, Web of knowledge and PEDro have been searched. Quality
      assessment was conducted using the 9-item Delphi list. Data extraction was
      performed by the first author. Effect sizes have been calculated using Cohen's d.
      RESULTS: 15 RCT's have been included. Most studies used add-on therapies. Almost
      all studies found improvements in both groups, but only 7 trials showed
      statistically significant between group differences in favor of the experimental
      group. Large effect sizes were found in only four studies. CONCLUSIONS: All the
      interventions discussed in this review can reduce the symptoms of UNS. However,
      TENS, optokinetic stimulation, somatosensory electrostimulation, mirror therapy
      and virtual reality training seem to be the most effective treatment methods (d >
      0,80). Future research should focus on producing studies of higher methodological
      quality with larger sample sizes.

PMID- 24018366
TI  - Impact of specific symptoms of spasticity on voluntary lower limb muscle
      function, gait and daily activities during subacute and chronic spinal cord
      injury.
AB  - BACKGROUND: Although the spasticity syndrome is an important sensorimotor
      disorder, the impact of grade of lower limb muscle hypertonia, spasm and clonus
      activity on voluntary muscle function, gait and daily activities has not been
      systematically analysed during subacute and chronic spinal cord injury (SCI).
      OBJECTIVE: To determine the prevalence of spasticity signs and symptoms during
      SCI, and to assess their impact on motor function and activities. METHODS: A
      descriptive transverse study of sixty-six subjects with SCI was performed by
      assessing injury characteristics, spasticity (modified Ashworth scale, Penn
      scale, SCATS scale) and motor function (lower limb manual muscle scores, WISCI
      II, spinal cord injury spasticity evaluation tool). RESULTS: Most subjects with
      the spasticity syndrome presented lower limb hypertonia and spasms during both
      subacute and chronic SCI, interfering with daily life activities. Subjects with
      incomplete SCI and hypertonia revealed a loss of voluntary flexor muscle
      activity, while extensors spasms contributed strongly to loss of gait function.
      The Penn spasms scale no correlated with muscle function or gait. CONCLUSIONS:
      Specific diagnosis of spasm activity during subacute SCI, and its impact on lower
      limb voluntary muscle activity, gait function and daily activities, is required
      to develop a more effective neurorehabilitation treatment strategy.

PMID- 24018367
TI  - Cognitive ability predicts motor learning on a virtual reality game in patients
      with TBI.
AB  - BACKGROUND: Virtual reality games and simulations have been utilized successfully
      for motor rehabilitation of individuals with traumatic brain injury (TBI). Little
      is known, however, how TBI-related cognitive decline affects learning of motor
      tasks in virtual environments. OBJECTIVE: To fill this gap, we examined learning
      within a virtual reality game involving various reaching motions in 14 patients
      with TBI and 15 healthy individuals with different cognitive abilities. METHODS:
      All participants practiced ten 90-second gaming trials to assess various aspects
      of motor learning. Cognitive abilities were assessed with a battery of tests
      including measures of memory, executive functioning, and visuospatial ability.
      RESULTS: Overall, participants with TBI showed both reduced performance and a
      slower learning rate in the virtual reality game compared to healthy individuals.
      Numerous correlations between overall performance and several of the cognitive
      ability domains were revealed for both the patient and control groups, with the
      best predictor being overall cognitive ability. CONCLUSIONS: The results may
      provide a starting point for rehabilitation programs regarding which cognitive
      domains interact with motor learning.

PMID- 24018368
TI  - Effects of information and training provision in satisfaction of patients and
      carers in stroke rehabilitation.
AB  - BACKGROUND: Active information and training improves patient and carer knowledge
      of stroke and aspects of patient satisfaction, as well as reduces patient
      depression. OBJECTIVE: To evaluate the effect of a post-stroke information and
      carer training intervention provided in the rehabilitation hospital setting on
      patient and carers' satisfaction. METHODS: Nonrandomized, controlled trial with
      241 patients consecutively admitted in a post-stroke rehabilitation unit and
      their carers. The first 140 underwent a standard rehabilitation program (control
      group) and the 131 following attended an additional class (intervention group).
      Satisfaction was assessed with the Satisfaction Pound Scale administered by
      telephone 6 months after stroke in 74 patients and 85 carers from the control
      group and in 76 patients and 73 carers from the intervention group. RESULTS: Over
      80% of patients in both groups were satisfied with information, care and therapy
      during hospitalization. The amount of therapy and support at discharge were the
      issues that arouse greater dissatisfaction. Patient and carers' satisfaction with
      information, support and accessibility to rehabilitation team after hospital
      discharge improved after the intervention (p < 0.001). CONCLUSIONS: Systematic
      active information, training and community support provision for stroke patients
      and carers improves satisfaction with stroke rehabilitation programs and support
      received after hospital discharge.

PMID- 24018369
TI  - Does robot-assisted gait training ameliorate gait abnormalities in multiple
      sclerosis? A pilot randomized-control trial.
AB  - BACKGROUND: Gait disorders are common in multiple sclerosis (MS) and lead to a
      progressive reduction of function and quality of life. OBJECTIVE: Test the
      effects of robot-assisted gait rehabilitation in MS subjects through a pilot
      randomized-controlled study. METHODS: We enrolled MS subjects with Expanded
      Disability Status Scale scores within 4.5-6.5. The experimental group received 12
      robot-assisted gait training sessions over 6 weeks. The control group received
      the same amount of conventional physiotherapy. Outcomes measures were both
      biomechanical assessment of gait, including kinematics and spatio-temporal
      parameters, and clinical test of walking endurance (six-minute walk test) and
      mobility (Up and Go Test). RESULTS: 16 subjects (n = 8 experimental group, n = 8
      control group) were included in the final analysis. At baseline the two groups
      were similar in all variables, except for step length. Data showed walking
      endurance, as well as spatio-temporal gait parameters improvements after robot
      assisted gait training. Pelvic antiversion and reduced hip extension during
      terminal stance ameliorated after aforementioned intervention. CONCLUSIONS: Robot
      assisted gait training seems to be effective in increasing walking competency in
      MS subjects. Moreover, it could be helpful in restoring the kinematic of the hip
      and pelvis.

PMID- 24018370
TI  - Diadochokinetic movements differ between patients with Huntington's disease and
      controls.
AB  - BACKGROUND: Assessment of impaired motor behaviour serves as tool for diagnosis
      and for evaluation of progression of chronic neurodegeneration. METHODS: We
      measured performance of rapid alternating movements, simple and complex motion
      series with instruments in scored, drug naive patients with Huntington's disease
      and controls. OBJECTIVES: To compare device outcomes with the ones of controls
      and to correlate them with each other and with the disease symptoms. RESULTS:
      Patients showed lower peak velocities and longer intervals for performance of
      rapid alternating movements than the controls. On the right dominant side, a
      correlation was found between intervals needed for standardised alternating
      movement performance and the simple motion task outcomes in the patients. No
      relations to the rated disease symptoms appeared. CONCLUSION: Execution of
      alternating movements is disturbed in Huntington's disease. Performance of the
      simple motion task and realisation of alternating motions shares a need for low
      cognitive efforts. Both ask for a more automated motion execution. Therefore they
      were related to each other to a certain extent. Execution of complex movement
      series asks for higher cognitive load, as it demands aiming and planning of
      movement series with visual input. This motion pattern does not resemble to the
      realisation of rapid alternating movements.

PMID- 24018371
TI  - Usefulness of the volume-viscosity swallow test for screening dysphagia in
      subacute stroke patients in rehabilitation income.
AB  - BACKGROUND: Swallowing disorders affect up to 35-85% of patients with stroke.
      Dysphagia complications can lead to malnutrition, dehydration, bronchoaspirative
      pneumonia and death, and have impact on health care costs. OBJECTIVE: To evaluate
      the clinical screening capacity of the Volume Viscosity Swallow Test (V-VST) for
      oropharyngeal dysphagia and aspiration in a homogeneous stroke patient sample.
      METHODS: Cohort study of 52 stroke patients in a subacute phase. Piecemeal
      deglutition and oropharyngeal residue were considered signs of impaired efficacy
      and cough, fall in oxygen saturation and voice changes, signs of impaired safety.
      Sensitivity, specificity, positive and negative predictive values, accuracy and
      likelihood ratios were calculated for V-VST results and compared with those of
      videofluoroscopy (VFS), the gold standard for studies on swallowing disorders.
      RESULTS: The V-VST is a highly sensitive and specific test to detect aspiration
      with sensitivity of 88.2% and specificity of 71.4%; negative predictive value was
      92.6%; accuracy index was 0.74. Sensitivity and specificity for penetration were
      34.3% and 70.6%, respectively; accuracy was 32%. CONCLUSIONS: The V-VST is low in
      cost, easy to use and very sensitive, meeting the requirements of oropharyngeal
      dysphagia and aspiration screening test in subacute stroke patients.

PMID- 24018372
TI  - Cerebral activation evoked by the mirror illusion of the hand in stroke patients
      compared to normal subjects.
AB  - BACKGROUND: Mirror therapy (MT) was found to improve motor function after stroke,
      but its neural mechanisms remain unclear, especially in single stroke patients.
      OBJECTIVES: The following imaging study was designed to compare brain activation
      patterns evoked by the mirror illusion in single stroke patients with normal
      subjects. METHODS: Fifteen normal volunteers and five stroke patients with severe
      arm paresis were recruited. Cerebral activations during movement mirroring by
      means of a video chain were recorded with functional magnetic resonance imaging
      (fMRI). Single-subject analysis was performed using SPM 8. RESULTS: For normal
      subjects, ten and thirteen subjects displayed lateralized cerebral activations
      evoked by the mirror illusion while moving their right and left hand
      respectively. The magnitude of this effect in the precuneus contralateral to the
      seen hand was not dependent on movement speed or subjective experience. Negative
      correlation of activation strength with age was found for the right hand only.
      The activation pattern in stroke patients is comparable to that of normal
      subjects and present in four out of five patients. CONCLUSIONS: In summary, the
      mirror illusion can elicit cerebral activation contralateral to the perceived
      hand in the majority of single normal subjects, but not in all of them. This is
      similar even in stroke patients with severe hemiparesis.

PMID- 24018373
TI  - Trunk training exercises approaches for improving trunk performance and
      functional sitting balance in patients with stroke: a systematic review.
AB  - BACKGROUND: Trunk control has been identified as an important early predictor of
      functional outcome after stroke but there is insufficient evidence that proximal
      stability of the trunk is a pre-requisite for sitting and standing balance,
      walking, and functional activities. OBJECTIVE: We systematically reviewed the
      literature on trunk training exercises (TTE) in adult patients with stroke. To
      establish if TTE can improve trunk performance and sitting balance. METHODS:
      CENTRAL, MEDLINE, EMBASE, CINAHL, PEDro, REHABDATA Database, Scielo, Scopus, Web
      of Science, Trip Database, and Epistemonikos were searched and reference lists
      screened to identify randomised controlled trials (RCTs) of trunk training
      exercises in stroke survivors. Two reviewers independently screened references,
      selected relevant studies, extracted data, and assessed trial quality. The
      primary outcomes were trunk performance and sitting balance. Due to the
      heterogeneity of included studies meta-analysis was not possible. RESULTS: A
      total of 11 studies with 317 participants were analysed. Trunk training exercises
      showed a moderate evidence to improve trunk performance and dynamic sitting
      balance. CONCLUSIONS: Trunk training exercises, performed with either stable or
      unstable surface, could be a good rehabilitation strategy and might help
      improving trunk performance and dynamic sitting balance after stroke.

PMID- 24018374
TI  - Metabolites from intestinal microbes shape Treg.
AB  - Intestinal bacterial metabolites are an important communication tool between the
      host immune system and the commensal microbiota to establish mutualism. In a
      recent paper published in Science, Wendy Garrett and her colleagues report an
      exciting role of the three most abundant microbial-derived short-chain fatty
      acids (SCFA), acetic acid, propionic acid and butyric acid, in colonic regulatory
      T cell (cTreg) homeostasis.

PMID- 24018375
TI  - Driving vascular endothelial cell fate of human multipotent Isl1+ heart
      progenitors with VEGF modified mRNA.
AB  - Distinct families of multipotent heart progenitors play a central role in the
      generation of diverse cardiac, smooth muscle and endothelial cell lineages during
      mammalian cardiogenesis. The identification of precise paracrine signals that
      drive the cell-fate decision of these multipotent progenitors, and the
      development of novel approaches to deliver these signals in vivo, are critical
      steps towards unlocking their regenerative therapeutic potential. Herein, we have
      identified a family of human cardiac endothelial intermediates located in outflow
      tract of the early human fetal hearts (OFT-ECs), characterized by coexpression of
      Isl1 and CD144/vWF. By comparing angiocrine factors expressed by the human OFT
      ECs and non-cardiac ECs, vascular endothelial growth factor (VEGF)-A was
      identified as the most abundantly expressed factor, and clonal assays documented
      its ability to drive endothelial specification of human embryonic stem cell (ESC)
      derived Isl1+ progenitors in a VEGF receptor-dependent manner. Human Isl1-ECs
      (endothelial cells differentiated from hESC-derived ISL1+ progenitors) resemble
      OFT-ECs in terms of expression of the cardiac endothelial progenitor- and
      endocardial cell-specific genes, confirming their organ specificity. To determine
      whether VEGF-A might serve as an in vivo cell-fate switch for human ESC-derived
      Isl1-ECs, we established a novel approach using chemically modified mRNA as a
      platform for transient, yet highly efficient expression of paracrine factors in
      cardiovascular progenitors. Overexpression of VEGF-A promotes not only the
      endothelial specification but also engraftment, proliferation and survival
      (reduced apoptosis) of the human Isl1+ progenitors in vivo. The large-scale
      derivation of cardiac-specific human Isl1-ECs from human pluripotent stem cells,
      coupled with the ability to drive endothelial specification, engraftment, and
      survival following transplantation, suggest a novel strategy for vascular
      regeneration in the heart.

PMID- 24018376
TI  - The cholinergic anti-inflammatory pathway meets microRNA.
AB  - Acetylcholine is a cellular mediator selected early in evolution as a key
      neurotransmitter, but its other biological roles including immune-modulation
      remain to be elucidated. In a recent paper published in Cell Research, Sun et al.
      report that acetylcholine modulates cytokine production in macrophages via
      microRNA-124. 

PMID- 24018377
TI  - Parthenogenetic haploid embryonic stem cells produce fertile mice.

PMID- 24018378
TI  - Common and divergent functions of Beclin 1 and Beclin 2.
AB  - In a recent paper published in Cell, He and colleagues reported the
      identification and functional characterization of Beclin 2, a mammal-specific
      homolog of the evolutionarily conserved autophagy-regulatory and oncosuppressive
      factor Beclin 1. In spite of a non-negligible degree of sequence identity, Beclin
      1 and Beclin 2 differ from each other in multiple aspects, including their
      functional profile as well as the genomic organization of the respective loci. 

PMID- 24018380
TI  - "The cutting edge".

PMID- 24018379
TI  - Centrosomal protein FOR20 is essential for S-phase progression by recruiting Plk1
      to centrosomes.
AB  - Centrosomes are required for efficient cell cycle progression mainly by
      orchestrating microtubule dynamics and facilitating G1/S and G2/M transitions.
      However, the role of centrosomes in S-phase progression is largely unknown. Here,
      we report that depletion of FOR20 (FOP-related protein of 20 kDa), a conserved
      centrosomal protein, inhibits S-phase progression and prevents targeting of Plk1
      (polo-like kinase 1) to centrosomes, where FOR20 interacts with Plk1. Ablation of
      Plk1 also significantly induces S-phase defects, which are reversed by ectopic
      expression of Plk1, even a kinase-dead mutant, but not a mutant that fails to
      localize to centrosomes. Exogenous expression of centrosome-tethered Plk1, but
      not wild-type Plk1, overrides FOR20 depletion-induced S-phase defects
      independently of its kinase activity. Thus, these data indicate that recruitment
      of Plk1 to centrosomes by FOR20 may act as a signal to license efficient
      progression of S-phase. This represents a hitherto uncharacterized role of
      centrosomes in cell cycle regulation. 

PMID- 24018381
TI  - Anchoring foreign substances on live cell surfaces using Sortase A specific
      binding peptide.
AB  - A simple, rapid, and efficient live cell surface labeling method has been
      developed that uses a direct conjugation between Sortase A expressed transiently
      at the cell surface and Sortase A specific binding peptide. 

PMID- 24018382
TI  - Phenol-soluble modulins and staphylococcal infection.
AB  - Staphylococcus aureus is an important human pathogen and a leading cause of death
      worldwide. Phenol-soluble modulins (PSMs) have recently emerged as a novel toxin
      family defining the virulence potential of highly aggressive S. aureus isolates.
      PSMs have multiple roles in staphylococcal pathogenesis, causing lysis of red and
      white blood cells, stimulating inflammatory responses and contributing to biofilm
      development and the dissemination of biofilm-associated infections. Moreover, the
      pronounced capacity of PSMs to kill human neutrophils after phagocytosis might
      explain failures in the development of anti-staphylococcal vaccines. Here, we
      discuss recent progress made in our understanding of the biochemical and genetic
      properties of PSMs and their role in S. aureus pathogenesis, and suggest
      potential avenues to target PSMs for the development of anti-staphylococcal
      drugs. 

PMID- 24018383
TI  - Horizontal gene transfer in osmotrophs: playing with public goods.
AB  - Osmotrophic microorganisms, such as fungi and oomycetes, feed by secreting
      depolymerizing enzymes to process complex food sources in the extracellular
      environment, and taking up the resulting simple sugars, micronutrients and amino
      acids. As a consequence of this lifestyle, osmotrophs engage in the acquisition
      and protection of public goods. In this Opinion article, we propose that
      horizontal gene transfer (HGT) has played a key part in shaping both the
      repertoire of proteins required for osmotrophy and the nature of public goods
      interactions in which eukaryotic microorganisms engage.

PMID- 24018386
TI  - Guest editorial: guideline clearinghouse updates inclusion criteria.

PMID- 24018385
TI  - Viral evolution: fooling the coronavirus proofreading machinery.

PMID- 24018387
TI  - Nutrition 411: revisiting vitamin C and wound healing.

PMID- 24018388
TI  - Continence coach: let's hear it for American ingenuity.

PMID- 24018384
TI  - The ins and outs of hepatitis C virus entry and assembly.
AB  - Hepatitis C virus, a major human pathogen, produces infectious virus particles
      with several unique features, such as an ability to interact with serum
      lipoproteins, a dizzyingly complicated process of virus entry, and a pathway of
      virus assembly and release that is closely linked to lipoprotein secretion. Here,
      we review these unique features, with an emphasis on recent discoveries
      concerning virus particle structure, virus entry and virus particle assembly and
      release. 

PMID- 24018389
TI  - A quantitative, cross-sectional study of depression and self-esteem in teenage
      and young adult burn victims in rehabilitation.
AB  - Burns can have a negative physiological and emotional impact, particularly among
      teenage victims. To assess the presence of depression and level of self-esteem, a
      cross-sectional study was conducted among 63 teenage and young adult burn victims
      ages 12 to 20 years undergoing physical and psychological rehabilitation at the
      Outpatient Unit for Plastic Surgery and Burns at the Central Institute of the
      Clinicas Hospital of the Faculty of Medicine of the University of Sao Paulo, Sao
      Paulo, Brazil. Assessment instruments included Beck's Depression Inventory (BDI)
      and the Rosenberg Self-Esteem Scale (RSE). Internal consistency within and
      between the two scales was established via Cronbach's-alpha coefficient. All
      variables were analyzed using descriptive statistics, and the statistical
      difference between means was compared using Student's t-test. The majority of
      participants were female (38, 60.3%) and unmarried (59, 93.7%) with a mean total
      body surface area (TBSA) burn of 23.84%. Most burns (58, 92.10%) were the result
      of accidents and were located on the trunk (47, 74.6%), head (43, 68%), arms (41,
      65%), hands (38, 60%), neck (34, 54%), and forearm (29, 46%). Participants had
      received physical and psychological rehabilitation for an average of 124.74
      months (SD 63.67) from a multidisciplinary team. The majority of participants
      (33, 52.4%) reported functional and aesthetic after-effects and appraised their
      scar as visible (51, 81.0%). BDI results showed low levels or absence of
      depression (mean = 7.63, SD 8.72; scale 0 = no depression to 63 = serious
      depression); the RSE showed adequate levels of self-esteem (mean = 8.41, SD 4.74;
      scale 0-30, where higher scores indicate worst levels of self-esteem). Burn
      location did not affect depression (BDI: P = 0.26) or self-esteem (RSE: P =
      0.21). However, depression and self-esteem were more significant in participants
      who were not able to work and/or go to school than in those who were (BDI: P =
      0.04 and self-esteem RSE: P = 0.03). Contrary to the initial hypothesis, this
      population of teenage burn victims did not experience depression and low self
      esteem compared with the normal population described in the literature, which may
      demonstrate the importance of multidisciplinary rehabilitation programs. 

PMID- 24018390
TI  - A two-year retrospective review of suspected deep tissue injury evolution in
      adult acute care patients .
AB  - Suspected deep tissue injury (sDTI) was recently defined as a pressure ulcer
      category, and knowledge about the evolution of these ulcers is limited. The
      purpose of this single-site, 2-year, retrospective, IRB-approved study was to
      increase understanding of the evolution and outcomes of sDTI. Inclusion criteria
      were hospitalized patients, 18 years or older, with a sDTI confirmed by a wound
      care nurse. Patient charts and WOC nurse notes were examined and patient
      demographics and DTI variables abstracted. All patients received standardized,
      comprehensive care for pressure ulcer prevention and treatment. Seventy-seven
      (77) patients, average age 67.5 years (range 32-91 years), with 128 sDTIs were
      identified and included in the study. The majority were men (52, 67.5%) and non
      Hispanic Caucasian (68, 88.3%). Twenty-three (23, 31%) were overweight. The most
      common comorbidities were coronary artery disease (38, 50%) and diabetes mellitus
      (33, 43%), and the vast majority (67, 88.1%) had altered mobility (67, 88.1%),
      spent time in the intensive care unit (64, 84.2%), and were incontinent (64,
      84.2%). The most common areas involved were the sacrum (51, 39.8%) and the
      heel/Achilles region (37, 28.9%). Maroon-purple discoloration of intact skin was
      the most commonly documented presentation (115 ulcers, 89.9%). Average length of
      follow-up was 6 days (range 1 day to 14 weeks). At the final assessment, 85 sDTIs
      (66.4%) completely resolved or were progressing toward resolution, 31 remained
      unchanged and were still documented as purple-maroon discoloration or a blood
      filled blister, and deterioration to full-thickness tissue loss occurredin 12
      (9.3%). These observations may offer important insights into the evolution of
      sDTIs. Research is needed to identify sDTI risk factors and most effective
      protocols of care. 

PMID- 24018391
TI  - The development of national quality performance standards for disposable
      absorbent products for adult incontinence.
AB  - Disposable absorbent products are widely used in inpatient care settings and in
      the community to manage adult urinary and fecal incontinence, but few product
      standards exist to help guide their production or optimal use. Increasing costs
      and reduced revenues have caused a number of states to evaluate absorbent product
      use among persons who receive care at home with the assistance of the Medicaid
      Waiver Program, further increasing concerns about the lack of product performance
      standards. To address these issues, the National Association For Continence
      (NAFC) formed a council of experts and key stakeholders with the objective of
      establishing national, independent quality performance standards for disposable
      absorbent products provided by states to Waiver Program recipients. The Council
      consisted of representatives from five purposefully selected states, technical
      directors from six nonwoven product manufacturers, an officer of the nonwoven
      manufactures trade association, a delegate from an academic nursing program and
      professional societies, a family caregiver, and a patient representative.
      Following a consensus method and guidelines for use, nine specific
      recommendations were developed, posted for public comment, and further refined.
      Final recommendations for product performance assessment include: rewet rate (a
      measure of a product's ability to withstand multiple incontinent episodes between
      changes), rate of acquisition (a measure of the speed at which urine is drawn
      away from the skin by a product, product retention capacity (a measure of a
      product's capacity to hold fluid without rewetting the skin), sizing options,
      absorbency levels, product safety, closure technology, breathable zones (a
      measure of the air permeability across a textile-like fabric at a controlled
      differential pressure), and elasticity. The Council also set values for and
      recommended four quantifiable parameters, and the testing methodology associated
      with each, to help consumers and states evaluate absorbent products (medium adult
      size): Maximum Rewet Rate: <1.0-2.0 g for briefs and <0.5-1.0 g for underwear;
      Maximum Rate of Acquisition: <50-60 seconds for briefs and <35-45 seconds for
      underwear; Minimum Retention Capacity: >250 g for standard briefs or underwear
      and >400 g for premium briefs or underwear; and Breathability of Zones: Minimum
      of >100 cubic feet per minute. As these recommendations are implemented, research
      is needed to evaluate the impact on both cost and quality of care for further
      refinement and modifications, particularly as technology and knowledge is
      advanced. 

PMID- 24018392
TI  - Proceedings from the National Cancer Institute's Second International Workshop on
      the Biology, Prevention, and Treatment of Relapse After Hematopoietic Stem Cell
      Transplantation: part III. Prevention and treatment of relapse after allogeneic
      transplantation.
AB  - In the Second Annual National Cancer Institute's Workshop on the Biology,
      Prevention, and Treatment of Relapse after Hematopoietic Stem Cell
      Transplantation, the Scientific/Educational Session on the Prevention and
      Treatment of Relapse after Allogeneic Transplantation highlighted progress in
      developing new therapeutic approaches since the first relapse workshop. Recent
      insights that might provide a basis for the development of novel, practical
      clinical trials were emphasized, including utilization of newer agents,
      optimization of donor lymphocyte infusion (DLI), and investigation of novel
      cellular therapies. Dr. de Lima discussed pre-emptive and maintenance strategies
      to prevent relapse after transplantation, for example, recent promising results
      suggestive of enhanced graft-versus-tumor activity with hypomethylating agents.
      Dr. Schmid provided an overview of adjunctive strategies to improve cell therapy
      for relapse, including cytoreduction before DLI, combination of targeted agents
      with DLI, and considerations in use of second transplantations. Dr. Porter
      addressed strategies to enhance T cell function, including ex vivo activated T
      cells and T cell engineering, and immunomodulatory approaches to enhance T cell
      function in vivo, including exogenous cytokines and modulation of costimulatory
      pathways.

PMID- 24018393
TI  - Proceedings from the National Cancer Institute's Second International Workshop on
      the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell
      Transplantation: part II. Autologous Transplantation-novel agents and
      immunomodulatory strategies.
AB  - In the National Cancer Institute's Second International Workshop on the Biology,
      Prevention, and Treatment of Relapse after Hematopoietic Stem Cell
      Transplantation, the Scientific/Educational Session on Autologous Transplantation
      addressed the role of novel agents and immunomodulatory strategies in management
      of relapse after autologous hematopoietic stem cell transplantation (AHSCT).
      Concepts were illustrated through in-depth discussion of multiple myeloma, with
      broader discussion of areas relevant for relapse of other malignancies as well as
      in the setting of allogeneic transplantation. Dr. Hari provided an overview of
      the epidemiology of relapse after AHSCT in multiple myeloma, addressing clinical
      patterns, management implications, and treatment options at relapse, highlighting
      the implications of novel therapeutic agents in initial, maintenance, and relapse
      treatment. Dr. Avigan discussed current concepts in tumor vaccine design,
      including whole cell and antigen-specific strategies, use of an AHSCT platform to
      reverse tumor-associated immunosuppression and tolerance, and combining vaccines
      with immunomodulatory agents to promote establishment of durable antitumor
      immunity. Dr. Hsu reviewed the immunogenetics of natural killer (NK) cells and
      general NK biology, the clinical importance of autologous NK activity (eg,
      lymphoma and neuroblastoma), the impact of existing therapies on promotion of NK
      cell activity (eg, immunomodulatory drugs, monoclonal antibodies), and strategies
      for enhancing autologous and allogeneic NK cell effects through NK cell gene
      profiling. 

PMID- 24018394
TI  - Providing personalized prognostic information for adult leukemia survivors.
AB  - Prediction of subsequent leukemia-free survival (LFS) and chronic graft-versus
      host disease (GVHD) in adults with acute leukemia who survived at least 1 year
      after allogeneic hematopoietic cell transplantation is difficult. We analyzed
      3339 patients with acute myeloid leukemia and 1434 patients with acute
      lymphoblastic leukemia who received myeloablative conditioning and related or
      unrelated stem cells from 1990 to 2005. Most clinical factors predictive of LFS
      in 1-year survivors were no longer significant after 2 or more years. For acute
      myeloid leukemia, only disease status (beyond first complete remission) remained
      a significant adverse risk factor for LFS 2 or more years after transplantation.
      For lymphoblastic leukemia, only extensive chronic GVHD remained a significant
      adverse predictor of LFS in the second and subsequent years. For patients
      surviving for 1 year without disease relapse or extensive chronic GVHD, the risk
      of developing extensive chronic GVHD in the next year was 4% if no risk factors
      were present and higher if noncyclosporine-based GVHD prophylaxis, an HLA
      mismatched donor, or peripheral blood stem cells were used. Estimates for
      subsequent LFS and extensive chronic GVHD can be derived for individual patients
      or populations using an online calculator
      (http://www.cibmtr.org/LeukemiaCalculators). This prognostic information is more
      relevant for survivors than estimates provided before transplantation. 

PMID- 24018396
TI  - Targeting the finite-deformation response of wavy biological tissues with bio
      inspired material architectures.
AB  - The Particle Swarm Optimization algorithm driven by a homogenized-based model is
      employed to target the response of three types of heart-valve chordae tendineae
      with different stiffening characteristics due to different degrees of waviness of
      collagen fibril/fiber bundles. First, geometric and material parameters are
      identified through an extensive parametric study that produce excellent agreement
      of the simulated response based on simplified unit cell architectures with the
      actual response of the complex biological tissue. These include amplitude and
      wavelength of the crimped chordae microstructure, elastic moduli of the
      constituent phases, and degree of microstructural refinement of the stiff phase
      at fixed volume fraction whose role in the stiffening response is elucidated. The
      study also reveals potential non-uniqueness of bio-inspired wavy microstructures
      in attaining the targeted response of certain chordae tendineae crimp
      configurations. The homogenization-based Particle Swarm Optimization algorithm,
      whose predictions are validated through the parametric study, is then shown to be
      an excellent tool in identifying optimal unit cell architectures in the design
      space that exhibits very steep gradients. Finally, defect criticality of optimal
      unit cell architectures is investigated in order to assess their feasibility in
      replacing actual biological tendons with stiffening characteristics. 

PMID- 24018395
TI  - Proceedings from the National Cancer Institute's Second International Workshop on
      the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell
      Transplantation: Part I. Biology of relapse after transplantation.
AB  - In the National Cancer Institute's Second Workshop on the Biology, Prevention,
      and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the
      Scientific/Educational Session on the Biology of Relapse discussed recent
      advances in understanding some of the host-, disease-, and transplantation
      related contributions to relapse, emphasizing concepts with potential therapeutic
      implications. Relapse after hematopoietic stem cell transplantation (HSCT)
      represents tumor escape, from the cytotoxic effects of the conditioning regimen
      and from immunologic control mediated by reconstituted lymphocyte populations.
      Factors influencing the biology of the therapeutic graft-versus-malignancy (GVM)
      effect-and relapse-include conditioning regimen effects on lymphocyte populations
      and homeostasis, immunologic niches, and the tumor microenvironment;
      reconstitution of lymphocyte populations and establishment of functional immune
      competence; and genetic heterogeneity within the malignancy defining potential
      for clonal escape. Recent developments in T cell and natural killer cell
      homeostasis and reconstitution are reviewed, with implications for prevention and
      treatment of relapse, as is the application of modern genome sequencing to
      defining the biologic basis of GVM, clonal escape, and relapse after HSCT. 

PMID- 24018397
TI  - Kinetic and pH studies on human phenylethanolamine N-methyltransferase.
AB  - Phenylethanolamine N-methyltransferase (PNMT) catalyzes the conversion of
      norepinephrine (noradrenaline) to epinephrine (adrenaline) while, concomitantly,
      S-adenosyl-L-methionine (AdoMet) is converted to S-adenosyl-L-homocysteine. This
      reaction represents the terminal step in catecholamine biosynthesis and
      inhibitors of PNMT have been investigated, inter alia, as potential
      antihypertensive agents. At various times the kinetic mechanism of PNMT has been
      reported to operate by a random mechanism, an ordered mechanism in which
      norepinephrine binds first, and an ordered mechanism in which AdoMet binds first.
      Here we report the results of initial velocity studies on human PNMT in the
      absence and presence of product and dead end inhibitors. These, coupled with
      isothermal titration calorimetry and fluorescence binding experiments, clearly
      shown that hPNMT operates by an ordered sequential mechanism in which AdoMet
      binds first. Although the logV pH-profile was not well defined, plots of logV/K
      versus pH for AdoMet and phenylethanolamine, as well as the pKi versus pH for the
      inhibitor, SK&F 29661, were all bell-shaped indicating that a protonated and an
      unprotonated group are required for catalysis.

PMID- 24018398
TI  - Focusing on flu: adolescents' perspectives on school-located immunization
      programs for influenza vaccine.
AB  - INTRODUCTION: To describe adolescents' perspectives regarding the use of school
      located immunization programs (SLIP) for influenza vaccination. More importantly,
      adolescents were asked what factors would make them more or less likely to use a
      SLIP offering influenza vaccine. RESULTS: Participants were generally found to be
      knowledgeable about influenza and to have positive attitudes toward receiving the
      vaccine via SLIP. Students were more willing to participate in a SLIP if it were
      low cost or free, less time-consuming than going to a doctor, and if they felt
      they could trust vaccinators. Overall, high school and middle school students
      ranked the benefits of SLIP similarly to each other. METHODS: Focus groups using
      nominal group method were conducted with middle and high school students in a
      large, urban school district. Responses were recorded by each school, and then,
      responses were ranked across all participating schools for each question.
      CONCLUSIONS: A wide range of issues are important to middle and high school
      students when considering participation in SLIPs including convenience, public
      health benefits, trust in the program, program safety, and sanitary issues.
      Further research will be needed regarding the generalizability of these findings
      to larger populations of students.

PMID- 24018399
TI  - Oxygen-vacancy-induced antiferromagnetism to ferromagnetism transformation in
      Eu0.5Ba0.5TiO3-delta multiferroic thin films.
AB  - Oxygen vacancies (V(O)) effects on magnetic ordering in Eu0.5Ba0.5TiO3-delta
      (EBTO3-delta) thin films have been investigated using a combination of
      experimental measurements and first-principles density-functional calculations.
      Two kinds of EBTO3-delta thin films with different oxygen deficiency have been
      fabricated. A nuclear resonance backscattering spectrometry technique has been
      used to quantitatively measure contents of the V(O). Eu0.5Ba0.5TiO3 ceramics have
      been known to exhibit ferroelectric (FE) and G-type antiferromagnetic (AFM)
      properties. While, a ferromagnetic (FM) behavior with a Curie temperature of 1.85
      K has been found in the EBTO3-delta thin films. Spin-polarized Ti(3+) ions, which
      originated from the V(O), has been proven to mediate a FM coupling between the
      local Eu 4f spins and were believed to be responsible for the great change of the
      magnetic ordering. Considering the easy formation of V(O), our work opens up a
      new avenue for achieving co-existence of FM and FE orders in oxide materials.

PMID- 24018401
TI  - Chronic kidney disease induced dysfunction of high density lipoprotein.
AB  - Traditional risk factors do not account for increased cardiovascular disease in
      patients with chronic kidney disease (CKD), particularly individuals whose CKD
      has progressed to end-stage kidney disease requiring dialysis. CKD patients on
      dialysis show little to no cardiovascular benefits from lipid-lowering therapy
      and thus have an exaggerated residual cardiovascular risk. High density
      lipoprotein (HDL) quantity and functionality may explain some of the residual
      risk. CKD affects the composition and disrupts the functionality of HDL,
      including cholesterol acceptor function and inflammatory effects. Notably,
      although these HDL abnormalities prevail in CKD, they do not track together and
      thereby support the idea of separate and distinct mechanistic pathways for each
      critical function of HDL. Targeting individual perturbations in HDL function
      represents a novel approach to therapy in this population. 

PMID- 24018403
TI  - Classic imaging for polyangitis nodosa.

PMID- 24018402
TI  - Treatment of primary systemic necrotizing vasculitides: the role of biotherapies.
AB  - Treatments of systemic necrotizing vasculitides have progressed markedly over the
      past few decades. The first attempts to obtain better-adapted therapeutic
      strategies evaluated the indications of conventional drugs, and their abilities
      to prolong survival and prevent relapses, while decreasing the severity and
      number of side effects. The French Vasculitis Study Group, the European
      Vasculitis Study Group or the Vasculitis Clinical Research Consortium organized
      most of the prospective clinical trials that have contributed to optimizing
      targeted treatment strategies. Recent therapeutic strategies include:
      immunomodulating methods (e.g. plasma exchanges), products (e.g. intravenous
      immunoglobulins) or, more recently, new agents called biotherapies. Some of the
      latter, mainly anti-CD20 monoclonal antibodies, have achieved promising effects
      and are now being evaluated in prospective trials. 

PMID- 24018404
TI  - Seroprevalence of hepatitis B and immune response to hepatitis B vaccination in
      Chinese college students mainly from the rural areas of western China and born
      before HBV vaccination integrated into expanded program of immunization.
AB  - The prevalence of hepatitis B surface antigen (HBsAg) in a population aged 15 y
      or older was high in China, but an immunization strategy for this population was
      unavailable. We investigated the seroprevalence of hepatitis B and immune
      response to HBV vaccine in Chinese college students (n=2040 participants), 11.1%,
      80.8%, and 8.1% had confirmed, unknown and no HBV vaccination history,
      respectively. The seropositive rates for HBsAg, anti-HBs sole and anti-HBs plus
      anti-HBc were 12.6%, 25.7%, and 30.1%, respectively. The HBsAg seropositive rate
      was significantly lower in participants with confirmed HBV vaccination history
      than in those with unknown or no vaccination history (5.3%, 13.6%, and 12.6%,
      respectively, P=0.0019). The anti-HBs alone seropositive rate was significantly
      higher in participants with confirmed HBV vaccination history than in those with
      unknown or no vaccination history (37.6%, 25.3%, and 13.8%, respectively,
      P<0.0001). Participants negative for HBsAg, anti-HBs, and anti-HBc at baseline
      (n=600) were given three doses of recombinant HBV vaccine (GlaxoSmithKline) at
      month 0, 1, and 6. Robust immune response was elicited after two and three doses
      (seroprotective rate: 91.9% and 99.0%, respectively, and geometric mean
      concentration [GMC]: 95.8 and 742.6 IU/L, respectively). Fourteen months after
      the third dose, the anti-HBs seroprotective rate of the group remained more than
      97%. The seroprotective rates and GMCs did not differ significantly by
      vaccination history. This study suggested that three doses of 20 MUg HBV vaccine
      were needed for college students negative for HBsAg, anti-HBs, and anti-HBc to
      ensure high seroprotective rates and concentrations.

PMID- 24018406
TI  - Water-controlled synthesis and single-crystal structural transformations of a
      cyanide-bridged W(IV)-Ni(II) molecular wheel complex and 3D networks.
AB  - One cyanide-bridged W(IV)-Ni(II) wheel-like complex and two three-dimensional
      (3D) networks can be directly synthesized based on K4[W(CN)8] and [Ni(L)](ClO4)2
      precursors by controlling the quantity of water in organic solvent. The water
      controlled single-crystal structural transformations among these complexes are
      described.

PMID- 24018405
TI  - Seroprevalence of pertussis in China: need to improve vaccination strategies.
AB  - Pertussis remains an important cause of infant death worldwide and is an ongoing
      public health concern even in countries with high vaccination coverage. A cross
      sectional seroepidemiological study was undertaken to estimate true incidence
      rates and gain further insight into the epidemiology and burden of pertussis in
      China. During 2011, a total of 1080 blood samples were obtained from healthy
      individuals between 0 and 86 y of age in Zhengzhou, Central China. Serum IgG
      antibodies against pertussis toxin (PT) and filamentous hemagglutinin (FHA) were
      measured quantitatively using ELISA. The results showed that the geometric mean
      titers of PT and FHA IgG were 6.48 IU/mL (95% CI: 5.70-7.41 IU/mL) and 11.39
      IU/mL (95% CI: 10.22-12.87 IU/mL) among subjects less than 4 y of age, indicating
      that pertussis antibody levels were low despite high vaccination coverage. Of the
      850 subjects>=4 y of age, 56 (6.6%) had anti-PT IgG titers above 30 IU/mL, and 11
      (1.3%) had antibodies titers above 80 IU/mL. The estimated age-specific incidence
      of infection with B. pertussis revealed a peak incidence in the 31 to 40 y age
      group, followed by the 41 to 60 y age group. Taken together, these results
      indicate that pertussis is common in Chinese subjects in Zhengzhou, especially in
      adults, suggesting that the disease burden is underestimated in China. Therefore,
      our study stresses the importance of strengthening the diagnostic capacity and
      improving surveillance system for delineating current epidemiological profiles of
      pertussis. Most importantly, it may be advisable to re-evaluate the current
      Chinese pertussis immunization schedule and implement to booster doses for older
      children, adolescents and adults.

PMID- 24018407
TI  - Dual RAS blockade-unresolved controversy?

PMID- 24018408
TI  - Dual RAS blockade-controversy resolved.

PMID- 24018409
TI  - Acute kidney injury: Urine output in AKI--the canary in the coal mine?

PMID- 24018410
TI  - Chronic kidney disease: Proteinuria as a predictor of rapid eGFR decline.

PMID- 24018411
TI  - Polycystic kidney disease: Trial of a long-acting somatostatin analogue for
      autosomal dominant polycystic kidney disease.

PMID- 24018412
TI  - Diabetes: Legacy effects of RAS blockade in diabetes mellitus.

PMID- 24018413
TI  - Chronic kidney disease: Blood pressure control in CKD--still a matter of debate.

PMID- 24018416
TI  - Elucidating the backbone conformation of photoswitchable foldamers using
      vibrational circular dichroism.
AB  - The backbone conformation of amphiphilic oligo(azobenzene) foldamers is
      investigated using vibrational circular dichroism (VCD) spectroscopy on a mode
      involving the stretching of the N=N bonds in the backbone. From denaturation
      experiments, we find that the VCD response in the helical conformation arises
      mainly from through-space interaction between the N=N-stretch transition-dipole
      moments, so that the coupled-oscillator model can be used to predict the VCD
      spectrum associated with a particular conformation. Using this approach, we
      elucidate the origin of the VCD signals in the folded conformation, and can
      assign the observed partial loss of VCD signals upon photo-induced unfolding to
      specific conformational changes. Our results show that the N=N-stretch VCD
      response provides an excellent probe of the helical conformation of the N=N bonds
      in this type of switchable molecular system.

PMID- 24018417
TI  - Scanning tunneling microscopy of a polygrain Al-Pd-Re quasicrystal: study of the
      relative surface stability.
AB  - Scanning tunneling microscopy and x-ray photoemission spectroscopy on a polygrain
      icosahedral (i-) Al-Pd-Re quasicrystal (QC) show the formation of the twofold
      surfaces with symmetry and composition expected from the bulk. The predominant
      occurrence of the twofold surface on the polygrain i-QC having random grain
      orientation, as well as preferential formation of terrace edges, kinks and voids
      along the twofold axes, consistently indicates that the twofold surface, which
      has the highest atomic density, is the most stable among all the crystallographic
      planes.

PMID- 24018415
TI  - A comparative assessment and analysis of 20 representative sequence alignment
      methods for protein structure prediction.
AB  - Protein sequence alignment is essential for template-based protein structure
      prediction and function annotation. We collect 20 sequence alignment algorithms,
      10 published and 10 newly developed, which cover all representative sequence- and
      profile-based alignment approaches. These algorithms are benchmarked on 538 non
      redundant proteins for protein fold-recognition on a uniform template library.
      Results demonstrate dominant advantage of profile-profile based methods, which
      generate models with average TM-score 26.5% higher than sequence-profile methods
      and 49.8% higher than sequence-sequence alignment methods. There is no obvious
      difference in results between methods with profiles generated from PSI-BLAST PSSM
      matrix and hidden Markov models. Accuracy of profile-profile alignments can be
      further improved by 9.6% or 21.4% when predicted or native structure features are
      incorporated. Nevertheless, TM-scores from profile-profile methods including
      experimental structural features are still 37.1% lower than that from TM-align,
      demonstrating that the fold-recognition problem cannot be solved solely by
      improving accuracy of structure feature predictions. 

PMID- 24018414
TI  - Mechanisms of vascular calcification in CKD-evidence for premature ageing?
AB  - Ageing is a potent, independent risk factor for cardiovascular disease.
      Calcification of the vascular smooth muscle cell (VSMC) layer of the vessel media
      is a hallmark of vascular ageing. Young patients with chronic kidney disease
      (CKD) exhibit an extremely high cardiovascular mortality, equivalent to that seen
      in octogenarians in the general population. Even children on dialysis develop
      accelerated medial vascular calcification and arterial stiffening, leading to the
      suggestion that patients with CKD exhibit a 'premature ageing' phenotype. It is
      now well documented that uraemic toxins, particularly those associated with
      dysregulated mineral metabolism, can drive VSMC damage and phenotypic changes
      that promote vascular calcification; epidemiological data suggest that some of
      these same risk factors associate with cardiovascular mortality in the aged
      general population. Importantly, emerging evidence suggests that uraemic toxins
      may promote DNA damage, a key factor driving cellular ageing, and moreover, that
      these ageing mechanisms may reiterate some of those seen in patients with
      genetically induced progeric syndromes caused by nuclear lamina disruption. This
      new knowledge should pave the way for the development of novel therapies that
      target tissue-specific ageing mechanisms to treat vascular decline in CKD. 

PMID- 24018418
TI  - Long-term label retaining cells localize to distinct regions within the female
      reproductive epithelium.
AB  - The uterus is an extremely plastic organ that undergoes cyclical remodeling
      including endometrial regeneration during the menstrual cycle. Endometrial
      remodeling and regeneration also occur during pregnancy and following
      parturition, particularly in hemochorial implanting species. The mechanisms of
      endometrial regeneration are not well understood. Endometrial stem/progenitor
      cells are proposed to contribute to endometrial regeneration in both humans and
      mice. BrdU label retention has been used to identify potential stem/progenitor
      cells in mouse endometrium. However, methods are not available to isolate BrdU
      label-retaining cells (LRC) for functional analyses. Therefore, we employed a
      transgenic mouse model to identify H2B-GFP LRCs throughout the female
      reproductive tract with particular interest on the endometrium. We hypothesized
      that the female reproductive tract contains a population of long-term LRCs that
      persist even following pregnancy and endometrial regeneration. Endometrial cells
      were labeled (pulsed) either transplacentally/translactationally or
      peripubertally. When mice were pulsed transplacentally/translactationally, the
      label was not retained in the uterus. However, LRCs were concentrated to the
      distal oviduct and endocervical transition zone (TZ) following natural (i.e.,
      pregnancy/parturition induced) and mechanically induced endometrial regeneration.
      LRCs in the distal oviduct and endocervical TZ expressed stem cell markers and
      did not express ERalpha or PGR, implying the undifferentiated phenotype of these
      cells. Oviduct and endocervical TZ LRCs did not proliferate during endometrial re
      epithelialization, suggesting that they do not contribute to the endometrium in a
      stem/progenitor cell capacity. In contrast, when mice were pulsed peripubertally
      long-term LRCs were identified in the endometrial glandular compartment in mice
      as far out as 9 months post-pulse. These findings suggest that epithelial tissue
      of the female reproductive tract contains 3 distinct populations of epithelial
      cells that exhibit stem/progenitor cell qualities. Distinct stem/progenitor-like
      cells localize to the oviduct, endometrium, and cervix. 

PMID- 24018419
TI  - Determination of pK(a) values of a triptolide derivative and its impurities by
      pressure-assisted capillary electrophoresis.
AB  - A pressure-assisted capillary zone electrophoresis method was developed to
      determine the pKa values of a triptolide derivative (LLDT-246) and its
      impurities. The method was performed in an uncoated fused-silica capillary under
      the electric voltage of 18kV and 50mbar of external pressure applied
      simultaneously. A series of running electrolyte buffers were used with pH ranging
      between 2.2 and 10.0 with the constant ionic strength of 0.05M. The values of pKa
      of LLDT-246 and two impurities were calculated based on the pH dependence of
      effective mobilities (MUeff). The pKa value of LLDT-246 was in good agreement
      with that of determined by potentiometric titration method. 

PMID- 24018420
TI  - Futile treatments in intensive care units.

PMID- 24018421
TI  - Cohesin and the nucleolus constrain the mobility of spontaneous repair foci.
AB  - The regulation of chromatin mobility in response to DNA damage is important for
      homologous recombination in yeast. Anchorage reduces rates of recombination,
      whereas increased chromatin mobility correlates with more efficient homology
      search. Here we tracked the mobility and localization of spontaneous S-phase
      lesions bound by Rad52, and find that these foci have reduced movement, unlike
      enzymatically induced double-strand breaks. Moreover, spontaneous repair foci are
      positioned in the nuclear core, abutting the nucleolus. We show that cohesin and
      nucleolar integrity constrain the mobility of these foci, consistent with the
      notion that spontaneous, S-phase damage is preferentially repaired from the
      sister chromatid. 

PMID- 24018422
TI  - The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination
      DNA repair.
AB  - SUMO conjugation is known to occur in response to double-stranded DNA breaks in
      mammalian cells, but whether SUMO deconjugation has a role remains unclear. Here,
      we show that the SUMO/Sentrin/Smt3-specific peptidase, SENP7, interacts with the
      chromatin repressive KRAB-associated protein 1 (KAP1) through heterochromatin
      protein 1 alpha (HP1alpha). SENP7 promotes the removal of SUMO2/3 from KAP1 and
      regulates the interaction of the chromatin remodeler CHD3 with chromatin.
      Consequently, in the presence of CHD3, SENP7 is required for chromatin relaxation
      in response to DNA damage, for homologous recombination repair and for cellular
      resistance to DNA-damaging agents. Thus, deSUMOylation by SENP7 is required to
      promote a permissive chromatin environment for DNA repair. 

PMID- 24018424
TI  - Human papillomavirus and its influence on head and neck cancer predisposition.
AB  - Human papillomavirus (HPV) is a virus often infecting humans. It is often present
      on skin or mucous membranes. These diverse DNA viruses are often linked to many
      various benign and malignant neoplastic lesions. Over 40 types of HPV are
      transmitted through sexual contact and infect the anogenital region which might
      be secondly transmitted to the oral mucous. Over 150 HPV viruses are defined
      according to the invaded site. Oral papillomas are marked with numbers 6, 7, 11,
      16 and 32. Squamous cell papilloma is often found in laryngeal epithelial tumor
      associated with HPV-6 and HPV-11 and also HPV-16 in oral squamous cell carcinoma
      (OSCC). In the last 15 years OSCC has become more common in children and young
      adults. The role of HPV virus causing oral squamous cell carcinomas is more often
      realized, but people's lack of knowledge and risky sexual behavior is still the
      main factor in growing HPV infections. 

PMID- 24018423
TI  - Isolevuglandin-modified phosphatidylethanolamine is metabolized by NAPE
      hydrolyzing phospholipase D.
AB  - Lipid aldehydes including isolevuglandins (IsoLGs) and 4-hydroxynonenal modify
      phosphatidylethanolamine (PE) to form proinflammatory and cytotoxic adducts.
      Therefore, cells may have evolved mechanisms to degrade and prevent accumulation
      of these potentially harmful compounds. To test if cells could degrade
      isolevuglandin-modified phosphatidylethanolamine (IsoLG-PE), we generated IsoLG
      PE in human embryonic kidney 293 (HEK293) cells and human umbilical cord
      endothelial cells and measured its stability over time. We found that IsoLG-PE
      levels decreased more than 75% after 6 h, suggesting that IsoLG-PE was indeed
      degraded. Because N-acyl phosphatidylethanolamine-hydrolyzing phospholipase D
      (NAPE-PLD) has been described as a key enzyme in the hydrolysis of N-acyl
      phosphatidylethanoamine (NAPE) and both NAPE and IsoLG-PE have large aliphatic
      headgroups, we considered the possibility that this enzyme might also hydrolyze
      IsoLG-PE. We found that knockdown of NAPE-PLD expression using small interfering
      RNA (siRNA) significantly increased the persistence of IsoLG-PE in HEK293 cells.
      IsoLG-PE competed with NAPE for hydrolysis by recombinant mouse NAPE-PLD, with
      the catalytic efficiency (V(max)/K(m)) for hydrolysis of IsoLG-PE being 30% of
      that for hydrolysis of NAPE. LC-MS/MS analysis confirmed that recombinant NAPE
      PLD hydrolyzed IsoLG-PE to IsoLG-ethanolamine. These results demonstrate that
      NAPE-PLD contributes to the degradation of IsoLG-PE and suggest that a major
      physiological role of NAPE-PLD may be to degrade aldehyde-modified PE, thereby
      preventing the accumulation of these harmful compounds.

PMID- 24018425
TI  - [Theta rhythm recorded in the hippocampal formation in vitro].
AB  - Theta rhythm is the best synchronized EEG activity that can be recorded in the
      mammalian brain. Hippocampal formation (HPC) is considered to be the main
      structure involved in the generation of this activity. Numerous data indicate
      that theta rhythm is involved in long-term potentiation, spatial learning,
      spatial navigation, verbal and spatial working memory, REM sleep, locomotor
      activities, and sensori-motor integration. Since the discovery of cholinergically
      induced theta rhythm recorded from the hippocampal formation slices, central
      mechanisms underlying theta generation have been successfully studied in the in
      vitro conditions. Most of in vitro studies have been focused on the basic
      question regarding the similarities between cholinergically-induced theta
      oscillations and theta rhythm examined in the in vivo conditions. The results of
      these experiments have clearly demonstrated that the main properties of theta
      rhythm in both, in vitro and in vivo preparations are similar. The present review
      has one main objective: to characterize the basic mechanisms underlying the
      generation of theta rhythm in the hippocampal formation maintained in vitro. 

PMID- 24018426
TI  - [Neuropeptides Y, YY, PP and their clinical significance].
AB  - peripheral nervous system. Considering the structure and evolutionary origin,
      neuropeptide Y (NPY) is a peptide of the same family as peptide YY (PYY) and
      pancreatic polypeptide (PP). These proteins were discovered relatively recently,
      however, knowledge about them is deepened. They are 36-amino acid peptide acting
      through G-protein coupled receptors, Y1, Y2, Y3, Y4, Y5 and Y6. The diverse
      structure C-terminus of the peptide and protein binding to receptors affect the
      biological activity and the physiological effects on the digestive system, blood
      vessels, and the center of hunger and satiety in the hypothalamus. Peptides have
      anorexic properties, they regulate appetite and food intake mainly through the
      intestinal cerebrospinal axis and the hypothalamus. These substances represent an
      important potential target of new drugs in the long-term treatment and prevention
      of obesity. Furthermore, neuropeptide Y affects many processes depending on the
      central nervous system modifies ethanol consumption, affect circadian rhythms,
      memory processes, anxiety behavior. Peripherally NPY affects smooth muscle
      contraction of the blood vessels, blood pressure, and atherogenic processes.
      Conducted more thorough research trying to define the role and participation of
      various neuropeptides in the development of diseases of the pancreas and the
      gastrointestinal tract, cardiovascular system and use it for diagnosis. 

PMID- 24018427
TI  - Effect of allograft inflammatory factor-1 gene polymorphisms on rheumatoid
      arthritis treatment with methotrexate.
AB  - OBJECTIVE: Methotrexate (MTX) in low doses is used in the therapy of rheumatoid
      arthritis (RA). The aim of many studies is to identify factors predicting the
      outcome of treatment with methotrexate in rheumatoid arthritis. The action of MTX
      in RA is associated with the inhibition of inflammatory mediators synthesis. AIF
      1 is a cytokine playing a role in chronic inflammatory processes. The levels of
      AIF-1 were significantly increased in synovial fluid from patients with RA. The
      aim of this study was to investigate the association between AIF1 gene
      polymorphisms (rs2269475:C>T, rs2736182:G>A, rs2259571:A>C) and response to
      treatment of RA patients with MTX. MATERIAL AND METHODS: The study was carried
      out on 221 patients diagnosed with active rheumatoid arthritis, treated with MTX.
      Good responders were defined as patients who were receiving MTX and had a DAS28
      of <=2.4 at 6 months. RESULTS: With regard to the AIF1 rs2259571 polymorphism the
      remission of RA symptoms was observed in 52.99% of AA genotype carriers, in
      45.25% of subjects with AC genotype, and in 32.84% with CC. The differences were
      statistically significant. CC vs AA p=0.03, OR 0.41, 95%CI (0.18-0.92).
      CONCLUSION: The results of this study suggest that the patients with the
      rs2259571 CC AIF1 genotype have a poorer response to therapy with MTX.

PMID- 24018428
TI  - The use of physiotherapy in the regeneration of periapical bone structures of the
      teeth, prepared to load the prosthetic.
AB  - The aim of this work was to investigate whether the use of magnetoledotherapy
      will accelerate the elimination of osteolytic lesions of the dental periapical
      area, and provide for prosthetic treatment. What impact on time of healing does
      the inflammatory change location, type of treatment or patient's age have? 69
      patients underwent the examination. The problem of osteolytic lesions in the
      course of protracted or protracted acute dental periapical tissue inflammation
      was determined. Patients were divided into two research groups: group L - treated
      with magnetoledotherapy and group K - treated without the support of
      magnetoledotherapy. In the first group we applied the electromagnetic field,
      generated using the Viofor JPS Clinic apparatus. Our studies have confirmed the
      effectiveness of magnetoledotherapy in the accelerated decommissioning of the
      osteolytic lesion. This provides evidence of the appropriateness of this method
      in the treatment of protracted dental periapical tissue inflammation, in teeth
      qualified for prosthetic load. Magnetostimulation combined with LED energy is an
      adjunctive procedure, adopted in order to eliminate osteolytic inflammatory
      changes of dental periapical tissues. It can be used in all age groups with the
      same good result. After applying magnetoledotherapy, in the course of the dental
      periapical tissue repair process of tooth treated endodontically for the first
      time as well as reendodontically, no differences were found. This shows the
      opportunity of using magnetoledotherapy in all cases of protracted periapical
      tissue inflammation. 

PMID- 24018429
TI  - Assessment of dopamine (DA) synthesis rate in selected parts of the rat brain
      with central noradrenergic lesion after administration of 5-HT3 receptor ligands.
AB  - INTRODUCTION: The study objective was to determine the effect of central
      noradrenergic system lesions performed in the early extrafetal life period on
      dopamine synthesis in the rat brain. The content of L-dihydroxyphenylalanine (L
      DOPA) was assessed in the frontal lobe, thalamus, hypothalamus and brain stem of
      rats by high-pressure chromatography with electrochemical detection (HPLC/ED)
      after administration of 5-HT3 receptor ligands. MATERIAL AND METHODS: Adult male
      Wistar rats which underwent central noradrenergic lesions by DSP-4 administration
      (50 mg/kg m.c. i.p.) on day 1 and 3 of life received i.p. injections of the
      aromatic amino acid decarboxylase inhibitor (NSD-1050) in a dose of 100 mg/kg
      b.w. Next, 30 min after NSD-1050 injection, the animals were decapitated by
      guillotine. Selected brain structures were dissected and L-DOPA content was
      determined by HPLC/ED. RESULTS AND CONCLUSIONS: A statistically significant
      reduction was found in DA synthesis in the group of animals with DSP-4 lesions
      induced by PBG (1-phenylbiguanide, 7.5 mg/kg b.w. i.p.) and ondansetron (1.0
      mg/kg b.w. i.p.). Morphine and PBG had no major effect on DA synthesis in the
      cerebral cortex of both control animals and in rats with noradrenergic lesions.
      The assessment of the effect of DSP-4 lesions on L-DOPA content in the brain stem
      after administration of morphine (7.5 mg/kg b.w. s.c.), PBG (7.5 mg/kg b.w. i.p.)
      or ondansetron (1.0 mg/kg b.w. i.p.) separately or jointly showed a statistically
      significant increase in the synthesis of DA in animals with DSP-4 lesions, as
      compared to the control group exposed to 0.9% NaCl and morphine. The analysis of
      the effect of DSP-4 lesions on L-DOPA content in the thalamus and hypothalamus
      revealed no statistically significant differences between the control groups of
      rats and those with DSP-4 lesions. As shown by this model, permanent
      noradrenergic lesions in animals in the early extra-fetal period result in
      increased reactivity of the central dopamine system.

PMID- 24018430
TI  - [Diabetes type 2 and Alzheimer disease - one or two diseases? Mechanisms of
      association].
AB  - Some epidemiological data and pathophysiological evidence suggest similarities
      and connection of two amyloidoses: diabetes mellitus type 2, (DM2) (non-insulin
      dependent diabetes mellitus, NIDDM) and Alzheimer's disease (AD). What they have
      in common is insulin resistance, neurodegeneration, development and progression
      of dementia, and the fact that in the course of both diseases fibrillar
      aggregates of specific proteins are accumulated in affected organs. What is more,
      experimental evidence also supports the hypothesis that small prefibrillar
      aggregates that emerge prior to the appearance of mature fibrils are responsible
      for a key step in development and cytotoxicity of both diseases. They also have
      similar pathogenic effects. Both peptides possess the common receptor AMY3. More
      and more evidence is accumulating that key cell regulation processes are similar
      for both diseases as well. The question is raised: can Alzheimer be a new form of
      diabetes disease? 

PMID- 24018431
TI  - [The synthesis of proteins in unnucleated blood platelets].
AB  - Platelets are the smallest, unnucleated blood cells that play a key role in
      maintaining normal hemostasis. In the human body about 1x1011 platelets are
      formed every day, as a the result of complex processes of differentiation,
      maturation and fragmentation of megakaryocytes. Studies done over 4 decades ago
      demonstrated that circulating in blood mature platelets can synthesize proteins.
      Recent discoveries confirm protein synthesis by unnucleated platelets in response
      to activation. Moreover, protein synthesis alters the phenotype and function of
      platelets. Platelets synthesize several proteins involved in hemostasis (COX,
      alphaIIbbeta3, TF PAI-1, Factor XI, protein C inhibitor) and in inflammatory
      process (IL-1beta, CCL5/RANTES). In spite of lack of transcription platelets have
      a stable mRNA transcripts with a long life correlated with platelet life span.
      Platelets also show expression of two important key regulators of translation
      eIF4E and EIF-2alpha and have a variety of miRNA molecules responsible for
      translational regulation. This article describes the historical overview of
      research on protein synthesis by platelets and presents the molecular mechanisms
      of protein synthesis in activated platelets (and synthesis of the most important
      platelet proteins). 

PMID- 24018432
TI  - [Schwann cells in therapy of spinal cord injuries].
AB  - Schwann cells (SC) have a special activity in the repair processes after injury
      of the nervous system because of the capability of differentiation, migration,
      proliferation and myelinization of axons. They enhance production of numerous
      neurotrophic factors, thus creating a permissive environment for axonal
      regeneration. Experimental studies using SC in neuronal transplants showed that
      these cells with their basal membrane with adhesion molecules are attractive
      material for neural prostheses facilitating axon growth. Moreover, SC can produce
      stable myelin, restoring normal function of the neuron. Transplantations of SC in
      myelin injury have been used in animal models of multiple sclerosis, Parkinson's
      disease, and brain and spinal cord injuries. Because the transplanted SC have no
      ability to migrate within the normal nervous system, in many experiments SC
      derived from rat embryos were applied. Such cells migrated through normal nervous
      tissue and co-operated with host cells, their survival was longer, and myelin was
      not destroyed in multiple sclerosis. Also, fast recovery of motor activity in
      injured axons in rat spinal cord was observed, especially after transplantation
      of SC derived from skin progenitor cells or progenitor cells which have a
      phenotype characteristic for SC. Many authors have reported early apoptosis of
      transplanted SC, so a more complex repair strategy is needed that combines SC
      transplantation with other methods in order to achieve longer survival and
      optimal functional recovery following spinal cord injury. 

PMID- 24018433
TI  - Red blood cell deformability and aggregation in chronic venous disease patients
      with varicose veins.
AB  - INTRODUCTION: Red blood cells' (RBC) rheological properties are disturbed in
      chronic venous disease (CVD). The aim of the study was to compare deformability
      and aggregation of erythrocytes taken from the varicose vein and the antecubital
      vein of patients with chronic venous disease. MATERIALS AND METHODS: Blood
      samples were taken from twelve CVD patients presenting clinical, aetiological,
      anatomical and pathological elements (CEAP) stages II and III. Blood was sampled
      from varicose veins and antecubital veins of patients (as control). Deformability
      and aggregation of RBC were analysed with a Laser-assisted Optical Rotational
      Cell Analyser (LORCA). RESULTS: A significant increase in deformability was found
      in varicose vein RBC for shear stress values 4.24, 8.23 and 15.96 Pa as compared
      to RBC from the antecubital vein. The aggregation index was significantly lower
      and aggregation halftime was significantly increased for RBC taken from
      antecubital veins than for RBC from varicose veins. DISCUSSION: In conclusion,
      RBC taken from varicose and antecubital veins of CVD patients are not entirely
      rheologically comparable and show different deformability and aggregation.
      Varicose vein RBC are more deformable and show a higher tendency for aggregation
      than antecubital vein RBC. Perhaps the deformability of varicose vein RBC has
      been increased as a compensation mechanism in subjects with CVD, due to increased
      resistance in their microcirculation.

PMID- 24018434
TI  - [The diagnostic importance of the new marker KIM-1 in kidney damage].
AB  - In recent years, the rapid development of scientific research led to the
      introduction of strategies based on new markers that allow for estimation of the
      latent disease period before the clinical symptoms of actual kidney failure are
      revealed. The experimental tests carried out on animals and cell lines derived
      from the proximal tubule have made possible the detection of genes that are
      induced early after hypoxia. The protein products of these genes can be
      considered as useful markers for the diagnosis of renal failure. The induction of
      gene KIM-1 (called Kidney Injury Molecule-1) results in the formation of protein
      that can be considered as a diagnostic marker. This work describes the data on
      the structure, biological function and importance of determining the
      concentrations of KIM-1 in the diagnosis of drug-induced toxicity and kidney
      damage.

PMID- 24018435
TI  - [Pharmacotherapy of Parkinson's disease: progress or regress?].
AB  - Parkinson's disease (PD) is a chronic, progressive disease of the central nervous
      system (CNS), characterized by a slow loss of dopaminergic neurons in the
      substantia nigra, leading to significant decrease in dopamine (DA) levels in the
      striatum. Currently used drugs, such as levodopa (L-DOPA), amantadine, dopamine
      agonists (D) or anticholinergic drugs, are not effective enough, and do not
      eliminate the causes of disease. Many research centers are conducting research on
      new forms of currently used drugs (e.g. Duodopa, XP21279, IPX066), new drugs of
      already known groups (e.g. safinamide), medicines that suppress side effects of L
      DOPA (e.g. AFQ056, fipamezole), and, finally, compounds with a novel mechanism of
      action (e.g. PMY50028, A2A receptor antagonists). A lot of scientific reports
      indicate an important role of A2A receptors in the regulation of the central
      movement system, so a new group of compounds - selective antagonists of A2A
      receptors (e.g. istradefylline, preladenant, SYN115) - has been developed and
      their potential use in PD has been examined. Clinical studies of A2A receptor
      antagonists have shown that this group of compounds can shorten off periods and
      at the same time they do not worsen dyskinesias in patients with PD. Moreover,
      there is ongoing research on new forms of treatment, such as gene therapy.
      Attempts to apply the viral vector AAV-2, which will be able to infect neurons
      with a variety of genes, including the gene of glutamate decarboxylase (GAD),
      neurturin (NTN), or aromatic L-amino acid decarboxylase, are currently being
      carried out. The results of phase I and II clinical studies showed some efficacy
      of this form of treatment, but the method requires further studies. An analysis
      of potential future therapies of Parkinson's disease suggests that some progress
      in this field has been made. 

PMID- 24018436
TI  - [New cytochrome P450 isoforms as cancer biomarkers and targets for
      chemopreventive and chemotherapeutic agents].
AB  - Cytochromes P450 (P450) are a multigene family of enzymes possessing a central
      role in the oxidative metabolism of a wide range of xenobiotics, including
      anticancer drugs, and endogenous compounds. The activity of different P450
      isoforms varies within specific tissues and cell types and is selectively
      regulated together with their gene expression. Moreover, differential expression
      of certain P450 isoforms' genes in tumor cells compared to normal tissues can be
      observed. This creates the potential for the use of these isozymes as tumor
      markers or selective prodrug activators. This article discusses the
      characteristics and function of five isoforms of cytochrome P450 (P450 1B1, P450
      2W1, P450 2S1, P450 2R1, P450 2U1) that could be potential targets for tumor
      therapeutic and preventive strategies. These isoforms have been chosen because
      their level of expression in tumor tissues is definitely higher than in normal
      tissues. 

PMID- 24018437
TI  - Fungal urinary tract infection complicated by acute kidney injury in an infant
      with intestino-vesical fistula.
AB  - We report one infant, who in the course of therapy of bacterial urinary tract
      infection developed fungal UTI and acute kidney injury. It was caused by
      coexistence of well-known risk factors and additionally intestino-vesical
      fistula. Appropriate and timely introduced treatment with intravenous fluconazole
      proved to be therapeutic in the patient. Our report shows that in every case
      detailed analysis of predisposing factors should be performed and appropriate
      diagnostic studies ordered, including the possible presence of other - less
      common - factors, e.g. defects in the gastrointestinal tract. 

PMID- 24018438
TI  - [Histone deacetylase inhibitors - molecular mechanisms of actions and clinical
      applications].
AB  - Histone deacetylases (HDACs) play an important role in the epigenetic regulation
      of gene expression implicated in cancer pathogenesis. Inhibitors of HDACs (HDI)
      are under investigation as novel anti-cancer drugs, which induce histone
      hyperacetylation. These agents modulate chromatin structure leading to
      transcriptional changes of a very large number of genes, which affect signaling
      pathways, inhibit cell cycle progression and angiogenesis, and induce apoptosis
      in cancer cells. Currently, several HDI are in clinical trials used in
      monotherapy or in combination with other cytostatics, showing promising
      anticancer effects. To date, more than 15 HDIs have been found as potential
      drugs. This paper reviews the molecular mechanisms of HDI action on cancer cells
      and summarizes clinical trials of the most promising HDIs in the treatment of
      patients with hematologic malignancies and solid tumors. 

PMID- 24018439
TI  - [Mechanism and risk factors of oral biofilm formation].
AB  - Recent microbiological investigations completely changed our understanding of the
      role of biofilm in the formation of the mucosal immune barrier and in
      pathogenesis of chronic inflammation of bacterial etiology. It is now clear that
      formation of bacterial biofilm on dental surfaces is characteristic for existence
      of oral microbial communities. It has also been proved that uncontrolled biofilms
      on dental tissues, as well as on different biomaterials (e.g. orthodontic
      appliances), are the main cause of dental diseases such as dental caries and
      periodontitis. The aim of this paper is to explain mechanisms and consequences of
      orthodontic biofilm formation. We will discuss current opinions on the influence
      of different biomaterials employed for orthodontic treatment in biofilm formation
      and new strategies employed in prevention and elimination of oral biofilm
      ("dental plaque"). 

PMID- 24018440
TI  - MMP-9 directed shRNAs as relevant inhibitors of matrix metalloproteinase 9
      activity and signaling.
AB  - INTRODUCTION: The main function of matrix metalloproteinases is the degradation
      of extracellular matrix components, which is related to changes in the
      proliferation of cells, their differentiation, motility, and death. MMPs play an
      important role in physiological processes such as embryogenesis, angiogenesis and
      tissue remodeling. The increase of MMPs activity is also observed in pathological
      conditions including tumorigenesis where MMP-2 (gelatinase A) and MMP-9
      (gelatinase B) show the ability to degrade the basement membrane of vessels and
      they are involved in metastasis. The aim of our study was to verify the changes
      of MMP-9 enzymatic activity and the mobility of cells after inhibition of MMP-9
      gene expression. MATERIAL AND METHODS: The oligonucleotide shRNA insert had been
      designed to silence MMP-9 gene expression and was cloned into the pSUPER.neo
      expression vector. The construct was introduced into the HeLa (CCL-2) cervical
      cancer cells by lipotransfection. Simultaneously in control cells MMP-9 were
      inhibited by doxycycline. Changes in activity of MMP-9 were analyzed by gelatin
      zymography and wound-healing assay. RESULTS/CONCLUSIONS: Gelatin zymography
      allowed us to confirm that activity of MMP-9 in cells transfected by shRNA-MMP-9
      and treated by doxycycline were similar and significantly lower in comparison
      with control cells. Phenotypic tests of migration in vitro confirm statistically
      significant (P<0.05) changes in cell migration - control cells healed 3 to 5
      times faster in comparison with transfected or doxycycline treated cells. Our
      studies show the significant role of MMP-9 in mobility and invasiveness of tumor
      cells, thus indicating a potential target point of interest for gene therapy.

PMID- 24018441
TI  - [AMP-activated protein kinase (AMPK) as therapeutic target].
AB  - AMP-activated protein kinase (AMPK) is one of the major energy sensor at both:
      cellular and whole body level. It exists as heterotrimer containing three
      subunits: the catalytic alpha subunit, beta and regulatory gamma. AMPK is
      localized both in the cytoplasm and in the nucleus. It is activated by increasing
      concentrations of AMP during the energy shortage, causing activation of catabolic
      pathways and inhibition of energy consuming processes. AMPK activity can be
      regulated allosterically: by binding AMP to a regulatory gamma subunit, as well
      as by phosphorylation on Thr172 of the catalytic alpha subunit by other kinases.
      Activated AMPK can effectively inhibit the mTOR pathway which is hyperactive in
      many types of cancer. On the other hand AMPK inactivation associates with the
      type II diabetes, diet-induced obesity, insulin resistance and the development of
      other metabolic disorders. The AMPK dysfunction is also observed in inflammation.
      It was discovered during last years that abnormalities in the AMPK function can
      induce the metabolic reprogramming in cancer cells known as the Warburg effect.
      Additionally, AMPK is activated during irradiation. Its activation leads to
      inhibition of growth. On the other hand, active AMPK enables cells to survive in
      difficult conditions such as hypoxia, or glucose deprivation. Because of its
      crucial role in maintaining of the energy homeostasis AMPK is an excellent
      therapeutic target. However, it still remains unknown what is better: to activate
      or inhibit the AMPK function. 

PMID- 24018442
TI  - Anesthesiology and the cytokine network.
AB  - The immune response is a highly specific reaction carried out by means of
      specialized cells that belong to the immune system. There are two types of immune
      response mechanisms aimed towards pathogens: non-specific, innate reactions, and
      specific, acquired reactions. Acquired immunity, characterized by its
      specificity, is comprised of lymphocytes, including both T cell and B cell
      populations. The role of B lymphocytes is not limited to the humoral response,
      though the cellular immune response is carried out mainly by various T lymphocyte
      subpopulations. The reactions of the humoral and cellular responses complement
      and stimulate one another mutually - cytokines are their common linking element.
      The attachment of cytokines to their specific receptors activates a sequence of
      signals - either intracellular or between the cells of various systems. This
      organization of respective connections and reactions, including the functional
      relations between cells of the immune response, in its complexity, is best
      described as a cytokine network. The response of the immune system to surgical
      trauma can be looked at from both a local and a general perspective. Not only
      surgical trauma caused by tissue damage, however, influences the functioning of
      the immune system, but also the drugs and techniques used during anesthesia. Our
      article is a presentation of the effects of medications used in anesthesia with
      respect to their influence on the cytokine network. 

PMID- 24018443
TI  - [Subclinical hypothyroidism in obese children].
AB  - Subclinical hypothyroidism (SH) is defined as an elevated thyroid stimulating
      hormone (TSH) associated with normal levels of free thyroxine. In obese persons
      prevalence of SH is significantly higher than in general population. SH is of
      particular interest in children with respect to the crucial role of thyroid
      hormones in the development of central nervous system and linear growth.
      Currently there is no general consensus on the treatment of SH with L-tyroxine.
      It is suggested that this hormonal state is rather a consequence that the cause
      of the overweight status. 

PMID- 24018444
TI  - [Properties and functional diversity of glyceraldehyde-3-phosphate
      dehydrogenase].
AB  - For a long time glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was considered a
      classical glycolytic protein of little interest. It was also used as a model
      protein for analysis of protein structure and enzyme mechanisms. However, recent
      evidence demonstrates that GAPDH from mammalian cells displays a number of
      diverse activities unrelated to its glycolytic function. This enzyme is an
      example of moonlighting protein. Dehydrogenase participates in membrane fusion,
      microtubule assembly, vesicular transport, and the maintenance of DNA integrity.
      New and novel studies indicate that enzyme is directly involved in
      transcriptional, posttranscriptional gene regulation, and the maintenance of
      chromatin structure. Furthermore, other studies also indicate a role of GAPDH in
      apoptosis, and age-related neurodegenerative disease e.g. Alzheimer's,
      Huntington's and Parkinson's diseases. This work describes the structure and
      localization of GAPDH in cells as well as the latest discoveries on the
      multifunctional properties of the enzyme. 

PMID- 24018445
TI  - [Tissue engineering - experimental method of urinary bladder regeneration].
AB  - The most common cause of bladder reconstruction is radical cystectomy for
      invasive bladder cancer. Currently, bowel segments remains, the most widely used
      in reconstruction of urinary tract. Using of bowel as a "material" for bladder
      reconstruction is associated with numerous complications. Tissue engineering
      methods provide opportunities to construct bladder tissue in vitro from
      autologous cells obtained from non urinary tract system. So far, the most useful
      cell and matrix type for bladder reconstruction have not been defined. In this
      work actual knowledge about tissue engineering in bladder regeneration was
      presented. 

PMID- 24018446
TI  - Milk-derived proteins and peptides in clinical trials.
AB  - Clinical trials are reviewed, involving proteins and peptides derived from milk
      (predominantly bovine), with the exception of lactoferrin, which will be the
      subject of another article. The most explored milk fraction is alpha-lactalbumin
      (LA), which is often applied with glycomacropeptide (GMP) - a casein degradation
      product. These milk constituents are used in health-promoting infant and adult
      formulae as well as in a modified form (HAMLET) to treat cancer. Lactoperoxidase
      (LCP) is used as an additive to mouth hygiene products and as a salivary
      substitute. Casein derivatives are applied, in addition, in the dry mouth
      syndrome. On the other hand, casein hydrolysates, containing active tripeptides,
      found application in hypertension and in type 2 diabetes. Lysozyme is routinely
      used for food conservation and in pharmaceutical products. It was successfully
      used in premature infants with concomitant diseases to improve health parameters.
      When used as prophylaxis in patients with scheduled surgery, it significantly
      reduced the incidence of hepatitis resulting from blood transfusion. Lysozyme was
      also used in infected children as an antimicrobial agent showing synergistic
      effects in combination with different antibiotics. Proline-rich polypeptide (PRP)
      was introduced to therapy of Alzheimer's disease patients. The therapeutic value
      of PRP was proved in several clinical trials and supported by studies on its
      mechanism of action. Concentrated immunoglobulin preparations from colostrum and
      milk of hyperimmunized cows showed efficacy in prevention of infections by
      bacteria, viruses and protozoa. A nutrition formula with milk-derived TGF-beta2
      (Modulen IBD(r)) found application in treatment of pediatric Crohn's disease. In
      conclusion, the preparations containing milk-derived products are safe and
      effective measures in prevention and treatment of infections as well as
      autoimmune and neoplastic diseases. 

PMID- 24018447
TI  - [Arsenic trioxide: impact on the growth and differentiation of cancer cells and
      possible use in cancer therapy].
AB  - Arsenic trioxide (As2O3) has recently been identified as an effective drug in
      different types of cancer therapy. It is a useful pharmacological agent in acute
      promyelocytic leukemia (APL) treatment, especially the form that is resistant to
      conventional chemotherapy with all-trans retinoic acid (ATRA). What is more,
      laboratory data suggest that As2O3 is also active when it comes to several solid
      tumor cell lines. However, the mechanism of action is not fully understood. As2O3
      in high doses triggers apoptosis, while in lower concentrations it induces
      partial differentiation. The As2O3 mechanism of action involves effects on
      mitochondrial transmembrane potential which lead to apoptosis. It also acts on
      the activity of JNK kinase, glutathione, caspases, NF-KB nuclear factor or pro-
      and antiapoptotic proteins. This publication presents the current knowledge about
      the influence of arsenic trioxide in cancer cells.

PMID- 24018448
TI  - Comparison of haptoglobin and alpha1-acid glycoprotein glycosylation in the sera
      of small cell and non-small cell lung cancer patients.
AB  - INTRODUCTION: Cancer-related carbohydrate epitopes, which are regarded as
      potential diagnostic and prognostic biomarkers, are carried on the main acute
      phase proteins. It is not clear, however, if the glycosylation profile is similar
      in different glycoproteins, or it is protein specific to some extent. The aim of
      the study was to compare fucosylation, alpha2,3 sialylation and expression of
      sialyl-Lewisx epitopes (sLe(x)) in the serum as a whole, AGP and haptoglobin of
      small cell (SCLC) and non-small cell lung cancer (NSCLC) patients with respect to
      healthy subjects as well as the cancer stage and its histological type. MATERIAL
      AND METHODS: Thirty-three NSCLC, 13 SCLC patients and 20 healthy volunteers were
      included in the study. Carbohydrate epitopes were detected by means of their
      reactivity with specific lectins and monoclonal anti-sLe(x) antibodies in direct
      or dual-ligand ELISA tests. RESULTS: Significantly increased fucosylation was
      found in total serum in both cancer groups and in NSCLC haptoglobin. No
      difference was observed in SCLC haptoglobin or alpha1-acid glycoprotein in both
      cancer groups. Also alpha2,3 sialylation was elevated in total serum, but not in
      alpha1-acid glycoprotein. This type of sialylation was undetectable in
      haptoglobin by means of MAA reactivity, in both healthy and cancer subjects.
      Complete sLe(x) antigens were overexpressed in total NSCLC serum and SCLC AGP,
      and their level was considerably lowered in cancer haptoglobin. DISCUSSION:
      Typical acute phase proteins, haptoglobin and AGP, exhibit different
      glycosylation profiles in lung cancer. Alterations observed in haptoglobin
      reflected the disease process better than those in AGP. Comparison of haptoglobin
      and AGP glycosylation to that observed in total serum suggests that some
      efficient carriers of disease-altered glycoproteins still remain unidentified.

PMID- 24018449
TI  - [The role of intestinal microflora and probiotic bacteria in prophylactic and
      development of colorectal cancer].
AB  - The gut microbiota comprises a large and diverse range of microorganisms whose
      activities have a significant impact on health. It interacts with its host at
      both the local and systemic level, resulting in a broad range of beneficial or
      detrimental outcomes for nutrition, infections, xenobiotic metabolism, and
      cancer. The current paper reviews research on the role of intestinal microflora
      in colorectal cancer development. Especially a protective effect of beneficial
      bacteria and probiotics on the risk of cancer development is highly discussed.
      There is substantial experimental evidence that the beneficial gut bacteria and
      their metabolism have the potential to inhibit the development and progression of
      neoplasia in the large intestine. Most of the data derive, however, from
      experimental and animal trials. Over a dozen well-documented animal studies have
      been published, wherein it has been clearly revealed that some lactic acid
      bacteria, especially lactobacilli and bifidobacteria, inhibit initiation and
      progression of colorectal cancer. Studies on cancer suppression in humans as a
      result of the consumption of probiotics are still sparse. Nevertheless, some
      epidemiological and interventional studies seem to confirm the bacterial
      anticancerogenic activity also in human gut. The mechanism by which probiotics
      may inhibit cancer development is unknown. Probiotics increase the amount of
      beneficial bacteria and decrease the pathogen level in the gut, consequently
      altering metabolic, enzymatic and carcinogenic activity in the intestine,
      decreasing inflammation and enhancing immune function, which may contribute to
      cancer defense. 

PMID- 24018450
TI  - Heart rate variability after BRL37344, a beta-3 agonist, in experimental bladder
      outlet obstruction.
AB  - INTRODUCTION: Bladder overactivity symptoms accompany benign prostatic
      hyperplasia (BPH) syndrome. The autonomic nervous system (ANS) disturbances may
      be involved in bladder dysfunction. An ameliorating effect on bladder
      overactivity is being assigned to the currently investigated beta-3
      adrenoreceptor agonists. However, little is known about the influence of beta-3
      agonists on ANS activity. The aim of our study was to estimate ANS activity using
      heart rate variability (HRV) in experimental model of bladder outlet obstruction
      (BOO), reflecting human BPH. MATERIAL/METHODS: 30 female rats, divided into
      control, non-treated BOO (LLBOO), and beta-3 agonist (BRL37344) BOO treated
      (LLBOO+beta3 agonist) were studied. BOO was evoked by 5-week long partial
      proximal urethra ligation. Next, 20-minute resting HRV recordings were performed
      in each of the studied groups following i.p. administration of the vehicle
      (LLBOO) or BRL37344 (LLBOO+beta3 agonist). RESULTS: LLBOO rats were characterized
      by diminished NN range, SDNN, and rMSSD in time-domain analysis. Similarly, TP
      and non-normalized spectral HRV parameters were also decreased. Contrary to these
      findings, normalized spectral parameters were lower (nLF) and higher (nHF). The
      animals treated with BRL37344 demonstrated no significant differences in time-
      domain HRV parameters. In spectral analysis, a decrease in LF and HF, together
      with a fall in TP, was found. Moreover, both nLF and nHF reached almost the same
      values in control and beta-3 agonist treated rats. DISSCUSSION: Our data
      indicates that BRL37344 is an agent abolishing the autonomic imbalance in
      experimental BOO, which may contribute to relieving the symptoms of bladder
      overactivity in beta-3 agonists treated participants.

PMID- 24018451
TI  - [Fullerenol - properties and applications in biomedical sciences].
AB  - Fullerenols, the water-soluble derivatives of fullerenes, are currently being
      recently intensively studied in the context of the possibility of their
      application in the biomedicine. Due to their hydrophilic properties and the
      ability to eliminate free radicals, fullerenols may in the future provide a solid
      alternative to currently used pharmacological methods in chemotherapy, treatment
      of neurodegenerative diseases and radiobiology. Depending on the research
      protocol applied, fullerenols may also act as pro oxidants. The dualistic nature
      of fullerenols may contribute to finding new biomedical applications of these
      agents in the future, by exerting a cytotoxic or protective effect respectively
      against cancer cells or healthy cells. Because of the encapsulated structure of
      fullerenols, there exists the possibility of their application in medical
      diagnostics in the transfer of contrast agents or in the drug transport. During
      the planning of an experiment designed to investigate the effects of radiation in
      combination with derivatives of water-soluble fullerenes, the possibility of
      appearance of the "dose-response effect" should be taken into consideration since
      it significantly contributes to one of the two possible effects: protection or
      sensitization. The same applies to the possibility of using these compounds as
      potential neuroprotectors. Fullerenol may protect neurons in the particular areas
      of the brain but in the definedcertain doses it may also induce cell death. A
      giant leap in the field of nanotechnology not only leads scientists to search for
      new applications of nanomaterials such as fullerenols, but also raises the
      question about their harmful effect on the environment. High utilization of
      hardly biodegradable fullerenols increases the likelihood of their accidental
      release into natural systems and their bioaccumulation. Despite convincing
      evidences about the potential applications of fullerenols in biomedicine, we
      still have insufficient knowledge about the mechanism of action of these
      molecules and their possible side effects. 

PMID- 24018452
TI  - Effect of vitamin D receptor gene (VDR) polymorphism on body height in children -
      own experience.
AB  - Genetic and environmental factors have an influence on the process of growth and
      development of the body. One of numerous genetic factors can be the vitamin D
      receptor gene (VDR). The study aimed at evaluating the relationship between VDR
      polymorphism and somatic parameters in children. PATIENTS AND METHODS: The study
      group consisted of 395 children, aged 6-18 years. All the patients underwent gene
      typing using the PCR-RFLP method within polymorphic loci BsmI (rs1544410), FokI
      (rs2228570), ApaI (rs7975232) and TaqI (rs731236) of the VDR receptor gene. 294
      children made up the control group in the study on the incidence of particular
      genotypes; in 161 patients somatic measurements of body weight and height were
      made with standard methods and skeletal densitometry (total body and spine
      programmes) examination was performed. Statistica 10.0 PL was used for
      statistical analysis. RESULTS: In patients with low bone mass a relationship
      between body height and FokI VDR polymorphism was noted. The p-value was
      statistically significantly different in group I (p=0.002) and borderline
      significant in group III (p=0.09). None of the polymorphisms of the VDR receptor
      gene demonstrated any statistically significant differences in anthropometric
      values in the control group and in children with osteoporosis. SUMMARY: The
      presence of the F allele of FokI polymorphism of the VDR receptor gene results in
      increased height, which is best observed in children with low bone mass. The FF
      genotype favours increased height in the study group of children from Lodz.

PMID- 24018453
TI  - The usefulness of flow cytometric analysis of cytokines in peripheral blood and
      bone marrow plasma.
AB  - INTRODUCTION: Recently attention has been paid to the role of cytokines in
      clinical pathology, since they can mediate a wide variety of biological effects.
      For these reasons multiplex methods have been developed to simultaneously measure
      numerous cytokines in individual small volume specimens. The aim of the study was
      to assess the usefulness of flow cytometric analysis of cytokines in peripheral
      blood and bone marrow plasma with Cytometric Bead Array (CBA) kits. MATERIAL AND
      METHODS: The study involved 59 children. Tests were performed in peripheral blood
      and bone marrow plasma. Human Inflammatory Cytokine Kit (IL-8, -1beta, -6, -10,
      TNF, -12p70) and Human Th1/Th2/Th17 Cytokine Kit (IL-2, -4, -6, -10, TNF, INF
      gamma, -17A) (BD Bioscience) were used. Samples were analyzed on a Cytomics FC500
      flow cytometer (Beckman Coulter). RESULTS: In patients diagnosed for
      hemophagocytic lymphohistiocytosis (HLH) (n=10) and for acute lymphoblastic
      leukemia (ALL) (n=12) Human Inflammatory Cytokine Kit was used. In almost all
      samples individual cytokines were detected in a wide range of concentrations
      (0.47 - 653.74 pg/ml). In samples from patients suffering from allergy (n=12) and
      in healthy children (n=25) Human Th1/Th2/Th17 Cytokine Kit was used. Detection of
      individual cytokines was much lower: concentration range 0.09-30.17 pg/ml.
      DISCUSSION: Based on our analysis the CBA test is suitable for analysis of
      several cytokines in small volumes of samples. A simple flow cytometer can be
      used for this test. The CBA test is more suitable for samples with expected
      increased levels of cytokines. When the levels of cytokines are low, the
      sensitivity of the CBA test can be too low.

PMID- 24018454
TI  - [Histamine in regulation of bone remodeling processes].
AB  - Bone remodeling is under autocrine, paracrine, endocrine and central nervous
      system control. One of the potential endogenous factors affecting bone remodeling
      is histamine, an endogenous amine which acts as a mediator of allergic reactions
      and neuromediator, and induces production of gastric acid. Histamine H1 receptor
      antagonists are widely used in the treatment of allergic conditions, H2 receptor
      antagonists in peptic ulcer disease, and betahistine (an H3 receptor antagonist
      and H1 receptor agonist) is used in the treatment of Meniere's disease. Excess
      histamine release in mastocytosis and allergic diseases may lead to development
      of osteoporosis. Clinical and population-based studies on the effects of
      histamine receptor antagonists on the skeletal system have not delivered
      unequivocal results. Expression of mRNA of histamine receptors has been
      discovered in bone cells (osteoblasts and osteoclasts). Histamine synthesis has
      been demonstrated in osteoclast precursors. Histamine increases bone resorption
      both by direct effects on osteoclast precursors and osteoclasts, and indirectly,
      by increasing the expression of RANKL in osteoblasts. In in vivo studies, H1 and
      H2 receptor antagonists exerted protective effects on the bone tissue, although
      not in all experimental models. In the present article, in vitro and in vivo
      studies conducted so far, concerning the effects of histamine and drugs modifying
      its activity on the skeletal system, have been reviewed.

PMID- 24018455
TI  - The activity of serum beta-galactosidase in colon cancer patients with a history
      of alcohol and nicotine dependence: preliminary data.
AB  - INTRODUCTION: Beta-galactosidase (GAL) is a lysosomal exoglycosidase involved in
      the catabolism of glycoconjugates through the sequential release of beta-linked
      terminal galactosyl residues. The stimulation of activity of exoglycosidases and
      other degradative enzymes has been noted in cancers as well as in alcohol and
      nicotine addiction separately. This is the first study to evaluate the activity
      of the serum senescence marker GAL in colon cancer patients with a history of
      alcohol and nicotine dependence, as a potential factor of worse cancer prognosis.
      MATERIAL AND METHODS: The material was serum of 18 colon cancer patients and 10
      healthy volunteers. Ten colon cancer patients met alcohol and nicotine dependence
      criteria. The activity of beta-galactosidase (pkat/ml) was determined by the
      colorimetric method. Comparisons between groups were made using the Kruskal
      Wallis analysis and differences evaluated using the Mann-Whitney U test.
      Spearman's rank correlation coefficient was used to measure the statistical
      dependence between two variables. RESULTS: The activity of serum GAL was
      significantly higher in colon cancer patients with a history of alcohol and
      nicotine dependence, in comparison to colon cancer patients without a history of
      drinking/smoking (p=0.015; 46% increase), and the controls (p=0.0002; 81%
      increase). The activity of serum GAL in colon cancer patients without a history
      of alcohol/nicotine dependence was higher than the activity in the controls (p =
      0.043; 24% increase). DISCUSSION/CONCLUSION: Higher activity of beta
      galactosidase may potentially reflect the accelerated growth of the cancer,
      invasion, metastases, and maturation, when alcohol and nicotine dependence
      coincide with colon cancer. For a better prognosis of colon cancer, alcohol and
      nicotine withdrawal seems to be required.

PMID- 24018456
TI  - [Alcohol dehydrogenase - physiological and diagnostic Importance].
AB  - Alcohol dehydrogenase (ADH) is a polymorphic enzyme, existing in multiple
      isoenzymes divided into several classes and localized in different organs. ADH
      plays a significant role in the metabolism of many biologically important
      substances, catalyzing the oxidation or reduction of a wide spectrum of specific
      substrates. The best characterized function of ADH is protection against excess
      of ethanol and some other exogenous xenobiotics and products of lipid
      peroxidation. The isoenzymes of alcohol dehydrogenase also participate in the
      metabolism of retinol and serotonin. The total alcohol dehydrogenase activity is
      significantly higher in cancer tissues than in healthy organs (e.g. liver,
      stomach, colorectum). The changes in activity of particular ADH isoenzymes in the
      sera of patients with different cancers (especially of the digestive system) seem
      to be caused by release of these isoenzymes from cancer cells, and may play a
      potential role as markers of this cancer. The particular isoenzymes of ADH
      present in the serum may indicate the cancer localization. Alcohol dehydrogenase
      may also be useful for diagnostics of non-cancerous liver diseases (e.g. viral
      hepatitis, non-alcoholic cirrhosis). 

PMID- 24018457
TI  - [Influence of natural gut flora on immune response].
AB  - Our intestines are habitat for trillions of microorganisms such as bacteria,
      viruses and eukaryotes, known as microbiota. They are indispensable for our well
      being due to their metabolic activities. Microbiota digests complex plant
      polysaccharides, which are normally unprocessed by humans; as well it retrieves
      other essential nutrients. It is well established that microbiota is crucial for
      proper development of intestinal as well systemic immune compartments. Recent
      results indicate that composition of natural gut flora is responsible for shaping
      of immune response. Alerted bacterial profile, known as dysbiosis precedes
      development of allergy in children. Many autoimmune conditions are associated
      with shift in intestinal bacterial profile. Apart of direct association between
      gut flora and systemic immune compartment little is known about the mechanisms by
      which microbiota exerts its immunoregulatory function. At the moment several
      bacterial strains as well some bacterial products were recognized as
      immunomodulators. This review describes the composition of normal gut flora as
      well disease-associated microbiota. It deals with unique mechanisms, found in
      GALT, that favor induction of tolerance towards orally administrated antigens as
      well discriminate between commensal and pathogens to minimize induction of
      inflammatory response. Further, the review tries to establish the connection
      between microbiota and systemic immune response. Finally the factors that
      modulate the composition of our gut flora are described. 

PMID- 24018458
TI  - The need to assay the real MIC when making the decision to eradicate
      Staphylococcus aureus with vancomycin.
AB  - PURPOSE: The aim of the study was a comparison of the MIC (minimal inhibitory
      concentration) evaluated in the automatic system Vitek 2 and the real MIC of
      vancomycin by the Etest method for S. aureus strains isolated from clinical
      materials. MATERIAL AND METHODS: Over a twelve-month study period we compared the
      results obtained with two commercial methods - the automatic system VITEK 2 and
      the real MIC by Etest - for 359 strains of S. aureus isolated from clinical
      materials. RESULTS: Most of the strains of S. aureus were cultured from wounds
      (84), the ear (60) and nose (42). MSSA (methicillin-sensitive Staphylococcus
      aureus) was isolated in 342 cases and MRSA (methicillin-resistant Staphylococcus
      aureus) in 17 cases. The test with the Vitek automatic method showed that
      vancomycin had MIC values of <=1.0 MUg/ml in more than 96% and 2.0 MUg/ml in over
      3% of cases. Using the Etest technique MIC <= 1.0 MUg/ml was obtained in only
      16.4% of cases and values of >1.0 MUg/ml in 83.6% of cases. DISCUSSION: In view
      of such big differences between the MIC values obtained with the two methods the
      authors suggest that the Etest method of assaying the real MIC is more useful
      than the automatic method.

PMID- 24018459
TI  - The frequency of myeloid and lymphoid dendritic cells in multiple myeloma
      patients is inversely correlated with disease progression.
AB  - Multiple myeloma (MM) is a neoplastic disease characterized by proliferation and
      prolonged survival of clonal plasma cells, most frequently occurring in the bone
      marrow, but also in other tissues. Dendritic cells (DCs) are a heterogeneous
      population of leukocytes defined as professional antigen presenting cells playing
      a key role in anticancer immunity. The purpose of this study was to evaluate
      subpopulations of myeloid and lymphoid DCs in the peripheral blood (PB) and bone
      marrow (BM) of patients with MM in the different clinical stages of MM and in
      correlation with known prognostic factors. The study involved 50 patients
      diagnosed with MM before the initiation of anticancer therapy and 25 individuals
      belonging to the control group. The mean percentage of myeloid and lymphoid DCs
      was determined using flow cytometry. In the present study, we demonstrated a
      significant reduction in the percentages of both myeloid and lymphoid DCs in MM
      patients, more pronounced in those with the worse prognosis as determined by the
      high levels of beta2 microglobulin. Accordingly, a marked decrease in the
      proportions of both myeloid and lymphoid DCs in the BM of patients with advanced
      clinical stage (III) compared to earlier stages (I+II) was also found. Our
      results suggest that the degree of DC subpopulations deficit could be related to
      the MM progression, which in consequence may contribute to the MM-related
      impairment of the immune responses. 

PMID- 24018460
TI  - Media-delivered cognitive behavioural therapy and behavioural therapy (self-help)
      for anxiety disorders in adults.
AB  - BACKGROUND: Anxiety disorders are the most common mental health problems. They
      are chronic and unremitting. Effective treatments are available, but access to
      services is limited. Media-delivered behavioural and cognitive behavioural
      interventions (self-help) aim to deliver treatment with less input from
      professionals compared with traditional therapies. OBJECTIVES: To assess the
      effects of media-delivered behavioural and cognitive behavioural therapies for
      anxiety disorders in adults. SEARCH METHODS: Published and unpublished studies
      were considered without restriction by language or date. The Cochrane Depression,
      Anxiety and Neurosis Review Group's Specialized Register (CCDANCTR) was searched
      all years to 1 January 2013. The CCDANCTR includes relevant randomised controlled
      trials from the following bibliographic databases: The Cochrane Library (all
      years), EMBASE (1974 to date), MEDLINE (1950 to date) and PsycINFO (1967 to
      date). Complementary searches were carried out on Ovid MEDLINE (1950 to 23
      February 2013) and PsycINFO (1987 to February, Week 2, 2013), together with
      International trial registries (the trials portal of the World Health
      Organization (ICTRP) and ClinicalTrials.gov). Reference lists from previous meta
      analyses and reports of randomised controlled trials were checked, and authors
      were contacted for unpublished data. SELECTION CRITERIA: Randomised controlled
      trials of media-delivered behavioural or cognitive behavioural therapy in adults
      with anxiety disorders (other than post-traumatic stress disorder) compared with
      no intervention (including attention/relaxation controls) or compared with face
      to-face therapy. DATA COLLECTION AND ANALYSIS: Both review authors independently
      screened titles and abstracts. Study characteristics and outcomes were extracted
      in duplicate. Outcomes were combined using random-effects models, and tests for
      heterogeneity and for small study bias were conducted. We examined subgroup
      differences by type of disorder, type of intervention provided, type of media,
      and recruitment methods used. MAIN RESULTS: One hundred and one studies with 8403
      participants were included; 92 studies were included in the quantitative
      synthesis. These trials compared several types of media-delivered interventions
      (with varying levels of support) with no treatment and with face-to-face
      interventions. Inconsistency and risk of bias reduced our confidence in the
      overall results. For the primary outcome of symptoms of anxiety, moderate-quality
      evidence showed medium effects compared with no intervention (standardised mean
      difference (SMD) 0.67, 95% confidence interval (CI) 0.55 to 0.80; 72 studies,
      4537 participants), and low-quality evidence of small effects favoured face-to
      face therapy (SMD -0.23, 95% CI -0.36 to -0.09; 24 studies, 1360 participants).
      The intervention was associated with greater response than was seen with no
      treatment (risk ratio (RR) 2.34, 95% CI 1.81 to 3.03; 21 studies, 1547
      participants) and was not significantly inferior to face-to-face therapy in these
      studies (RR 0.78, 95 % CI 0.56 to 1.09; 10 studies, 575 participants), but the
      latter comparison included versions of therapies that were not as comprehensive
      as those provided in routine clinical practice. Evidence suggested benefit for
      secondary outcome measures (depression, mental-health related disability, quality
      of life and dropout), but this evidence was of low to moderate quality. Evidence
      regarding harm was lacking. AUTHORS' CONCLUSIONS: Self-help may be useful for
      people who are not able or are not willing to use other services for people with
      anxiety disorders; for people who can access it, face-to-face cognitive
      behavioural therapy is probably clinically superior. Economic analyses were
      beyond the scope of this review.Important heterogeneity was noted across trials.
      Recent interventions for specific problems that incorporate clinician support may
      be more effective than transdiagnostic interventions (i.e. interventions for
      multiple disorders) provided with no guidance, but these issues are confounded in
      the available trials.Although many small trials have been conducted, the
      generalisability of their findings is limited. Most interventions tested are not
      available to consumers. Self-help has been recommended as the first step in the
      treatment of some anxiety disorders, but the short-term and long-term
      effectiveness of media-delivered interventions has not been established. Large,
      pragmatic trials are needed to evaluate and to maximise the benefits of self-help
      interventions.

PMID- 24018461
TI  - Does orthodontic treatment harm children's diets?
AB  - INTRODUCTION: Despite the many courses of fixed orthodontic treatment being
      undertaken worldwide, the question of this treatment harming children's diets
      remains unanswered. METHODS: A hospital-based prospective cohort design was
      adopted to investigate the effects of treatment on dietary intake and behaviour,
      body fat (BMI) and fat percentage in 124 patients (41.9% male) aged 11-14 (mean
      13.1, SD 0.91) years, consecutively recruited to test and control groups. Both
      groups completed socio-demographic and food frequency questionnaires, body mass
      index (BMI) and body fat percentage measures at baseline and follow-up. Test
      patients completed follow-up pain diaries and dietary questionnaires. RESULTS:
      Both groups were comparable at baseline, with a dropout rate of 12.1%. The impact
      on dietary behaviour was significantly higher at 6 weeks compared to 3 months
      (P<0.002). Pain (biological factor), analgesic consumption or professional
      dietary advice (behaviour modification) had no influence whilst, a high BMI
      status at baseline appeared to be the only significant moderator of change in fat
      percentage (P<0.05) and impacts on dietary behaviour (P<0.049) at follow-up.
      CONCLUSIONS: The findings show no significant detrimental effect on dietary
      intake or behaviour, BMI and fat percentage, during the first 3 months, of
      orthodontic treatment and may impart a beneficial/protective effect.

PMID- 24018462
TI  - Mineral content in teeth with deciduous molar hypomineralisation (DMH).
AB  - OBJECTIVES: We report the mineral (hydroxyapatite) density of sound and opaque
      areas in DMH molars with sound parts of (carious) deciduous teeth serving as
      controls. METHODS: Twenty-nine extracted second primary molars obtained from 15
      children were studied. Thirteen of these molars were DMH molars with yellow
      opacities, seven were DMH molars with white opacities, three DMH molars with
      brown opacities and eleven were molars without DMH. Prior to microCT scanning,
      the teeth were mounted in impression material (Impregum((r))) and stored in water
      with a thymol crystal. Spot analysis and line scans were performed in areas with
      opacities and in sound areas. An ANOVA test and t-tests were used to test if
      there were significant differences between the groups. RESULTS: The average
      densities of the hydroxyapatite in yellow and brown opacities (1368mg HA/cm(2)
      and 1407mg HA/cm(2), respectively) were significantly lower than in clinically
      unaffected enamel (1747mg HA/cm(2)) of DMH molars or of sound molars (1758mg
      HA/cm(2)). The mineral density in white opacities (1737mg HA/cm(2)) was not
      different from that in the enamel of sound molars. The mineral density values in
      yellow and brown enamel opacities were in between those of dentine (1018mg
      HA/cm(2)) and enamel. CONCLUSIONS: DMH molars with yellow or brown opacities had
      a 20-22% lower mineral density in the hypomineralised enamel compared with sound
      molars. White opacities do not show a lower mineral content. The reduction in
      enamel mineral content in DMH molars stressed the need for a preventive approach
      in DMH.

PMID- 24018463
TI  - Impact of various screwed implant prostheses on oral health-related quality of
      life as measured with the QoLIP-10 and OHIP-14 scales: a cross-sectional study.
AB  - OBJECTIVES: This study aimed to validate the Quality of Life with Implant
      Prostheses (QoLIP-10) questionnaire for assessing the impact of screwed implant
      supported rehabilitations on oral health-related quality of life (OHRQoL).
      METHODS: 131 patients wearing screw-retained implant restorations were assigned
      to the following groups: Group 1 (HP; n=50): fixed-detachable hybrid prostheses
      (control), Group 2 (S-PD; n=43): metal-ceramic screwed partial dentures, and
      Group 3 (S-CD; n=38): metal-ceramic screwed complete dentures. Impacts on OHRQoL
      were evaluated using the QoLIP-10 and Oral Health Impact Profile (OHIP-14sp)
      scales. Data on global oral satisfaction, socio-demographics, health-behaviours,
      and prosthetics were gathered. Reliability and validity of the QoLIP-10 were
      investigated for screwed prosthesis wearers. The Spearman's rank test was applied
      to determine the correlation between both indices. Descriptive and non-parametric
      probes were run to evaluate the influence of the study variables on OHRQoL.
      RESULTS: The QoLIP-10 confirmed its psychometric capacity for screwed prosthesis
      wearers. Both tests were inversely correlated. HP wearers reported the worst
      dental-facial aesthetics, performance, and functional limitation outcomes.
      Gender, education level, complaints about the mouth, perception of treatment
      needs, and prosthetic status modulated the OHRQoL. CONCLUSIONS: Screwed implants
      restorations provide better OHRQoL than do fixed-detachable hybrid prostheses.

PMID- 24018465
TI  - A facile and versatile approach to efficient enhancement of solid-state
      luminescence by organic-inorganic hybrid salts.
AB  - Organic-inorganic hybrid salts based on 1,5-bisaminophenylanthracene were able to
      overcome aggregation-induced quenching and emit multiple colours of luminescence
      according to the counter acid employed. Moreover, the emission colour could be
      reversibly and dynamically changed on absorption and desorption of guest
      molecules. 

PMID- 24018464
TI  - Systematic review of contracture reduction in the lower extremity with dynamic
      splinting.
AB  - INTRODUCTION: Joint contractures are relatively common disorders that can result
      in significant, long-term morbidity. Initial treatment is non-operative and often
      entails the use of mechanical modalities such as dynamic and static splints.
      Although widely utilized, there is a paucity of data that support the use of such
      measures. The purpose of this systematic review was to evaluate the safety and
      efficacy of dynamic splinting as it is used to treat joint contracture in lower
      extremities, and to determine if duration on total hours of stretching had an
      effect on outcomes. METHODS: Reviews of PubMed, Science Direct, Medline, AMED,
      and EMBASE websites were conducted to identify the term 'contracture reduction'
      in manuscripts published from January 2002 to January 2012. Publications selected
      for inclusion were controlled trials, cohort studies, or case series studies
      employing prolonged, passive stretching for lower extremity contracture
      reduction. A total of 354 abstracts were screened and eight studies (487
      subjects) met the inclusion criteria. The primary outcome measure was change in
      active range of motion (AROM). RESULTS: The mean aggregate change in AROM was
      23.5o in the eight studies examined. Dynamic splinting with prolonged, passive
      stretching as home therapy treatment showed a significant direct, linear
      correlation between the total number of hours in stretching and restored AROM. No
      adverse events were reported. DISCUSSION: Dynamic splinting is a safe and
      efficacious treatment for lower extremity joint contractures. Joint specific
      stretching protocols accomplished greater durations of end-range stretching which
      may be considered to be responsible for connective tissue elongation.

PMID- 24018466
TI  - A simple protocol for the synthesis of dinitrosyl iron complexes with
      glutathione: EPR, optical, chromatographic and biological characterization of
      reaction products.
AB  - The diamagnetic binuclear form of dinitrosyl iron complexes (B-DNIC) with
      glutathione can be easily synthesized in the air at ambient temperature. The
      synthetic protocol includes consecutive addition to distilled water of
      glutathione, which decreases the pH of the test solution to 4.0, a bivalent iron
      salt (e.g., ferrous sulphate) and sodium nitrite at the molar ratio of 2:1:1,
      with a subsequent increase in pH to neutral values. Under these conditions, the
      amount of B-DNIC formed is limited by initial nitrite concentration. In the novel
      procedure, 20mM glutathione, 10mM ferrous sulfate and 10mM sodium nitrite give
      2.5mM B-DNIC with glutathione, while 5mM glutathione remains in the solution.
      Bivalent iron (5mM) is precipitated in the form of hydroxide complexes, which can
      be removed from the solution by passage through a paper filter. After the
      increase in rN to 11 and addition of thiols at concentrations exceeding that of
      DNIC tenfold, B-DNIC are converted into a mononuclear EPR-active form of DNIC (M
      DNIC) with glutathione. B-DNIC preparations synthesized by using new method
      contain negligible amount of nitrite or S-nitrosoglutathione as a contaminations.
      All the steps of DNIC synthesis were characterized by using optical, EPR and HPLC
      methods. A long-lasting hypotensive action of DNIC formed was demonstrated. 

PMID- 24018467
TI  - The relationship between perceived discrimination and psychotherapeutic and
      illicit drug misuse in Chicago, IL, USA.
AB  - Based on several stress-coping frameworks, recent studies have suggested that
      perceived experiences of discrimination, a psychosocial stressor, may be
      associated with various risky health behaviors. The 2001 Chicago Community Adult
      Health Study (n = 3,101), a face-to-face representative probability sample of
      adults in Chicago, IL, USA, was used to examine the relationship among lifetime
      everyday discrimination, major discrimination, and the use of illicit and
      psychotherapeutic drugs for nonmedical reasons. We used negative binomial
      logistic and multinomial regression analyses controlling for potential
      confounders. Approximately 17 % of the respondents reported using one or more
      illicit drugs and/or misusing one or more psychotherapeutic drug. Adjusting for
      socio-demographic characteristics, other stressors and various personality
      related characteristics, results from negative binomial regression suggest that
      respondents who experienced moderate to high levels of everyday discrimination
      misused on average 1.5 different kinds of drugs more than respondents that
      experienced relatively low levels of everyday discrimination (p < 0.05).
      Similarly, an increase in one lifetime major discrimination event was associated
      with an increase of misusing 1.3 different drugs on average regardless of
      experiences of everyday discrimination (p < 0.001). When examining the types of
      drugs misused, results from multinomial logistic regression suggest that everyday
      discrimination was only associated with illicit drug use alone; however, lifetime
      major discrimination was associated with increased odds of using any illicit and
      both illicit/psychotherapeutic drugs. Mental health and substance use clinical
      providers should be aware of these potential relationships and consider
      addressing the harmful effects of perceived discrimination, in all patients not
      only among racial/ethnic minority patients. 

PMID- 24018468
TI  - The repertoire of MHC class I genes in the common marmoset: evidence for
      functional plasticity.
AB  - In humans, the classical antigen presentation function of major
      histocompatibility complex (MHC) class I molecules is controlled by the human
      leukocyte antigen HLA -A, HLA-B and HLA-C loci. A similar observation has been
      made for great apes and Old World monkey species. In contrast, a New World monkey
      species such as the cotton-top tamarin (Saguinus oedipus) appears to employ the G
      locus for its classical antigen presentation function. At present, little is
      known about the classical MHC class I repertoire of the common marmoset
      (Callithrix jacchus), another New World monkey that is widely used in biomedical
      research. In the present population study, no evidence has been found for
      abundant transcription of classical I class genes. However, in each common
      marmoset, four to seven different G-like alleles were detected, suggesting that
      the ancestral locus has been subject to expansion. Segregation studies provided
      evidence for at least two G-like genes present per haplotype, which are
      transcribed by a variety of cell types. The alleles of these Caja-G genes cluster
      in separate lineages, suggesting that the loci diversified considerably after
      duplication. Phylogenetic analyses of the introns confirm that the Caja-G loci
      cluster in the vicinity of HLA-G, indicating that both genes shared an ancestor.
      In contrast to HLA-G, Caja-G shows considerable polymorphism at the peptide
      binding sites. This observation, together with the lack of detectable transcripts
      of A and B-like genes, indicates that Caja-G genes have taken over the function
      of classical class I genes. These data highlight the extreme plasticity of the
      MHC class I gene system. 

PMID- 24018469
TI  - Antibody-cytokine fusion proteins for cancer immunotherapy: an update on recent
      developments.
AB  - Treatment with cytokines holds great potential for cancer immunotherapy, but is
      generally restricted by systemic toxicity. Tumor-directed targeting in the form
      of antibody fusion proteins appears to be an attractive strategy to overcome this
      problem. In the last twenty years, continuous efforts in developing appropriate
      molecules have retrieved a variety of antibody fusion proteins that reveal
      promising therapeutic effects in preclinical studies. Currently, several
      candidates are in clinical evaluation. Here, recent developments exploring
      diverse antibody formats, tumor targets and cytokines of different families as
      well as strategies addressing cytokine modification or presentation are discussed
      and clinical trials summarized at a glance. Thus, antibody-cytokine fusion
      proteins are becoming progressively improving immunologic reagents that raise
      expectations mainly for combinatorial cancer therapies. 

PMID- 24018470
TI  - Pegylated liposomal doxorubicin: a guide to its use in various malignancies.
AB  - Pegylated liposomal doxorubicin (Caelyx((r)) [EU], Doxil((r)) [USA]) represents
      an improved formulation of conventional doxorubicin, with reduced cardiotoxicity
      and an improved pharmacokinetic profile. As shown by evidence from clinical
      trials, intravenous pegylated liposomal doxorubicin is a useful option in the
      treatment of various malignancies, including metastatic breast cancer, ovarian
      cancer, multiple myeloma, and AIDS-related Kaposi sarcoma. It has a favourable
      safety profile relative to conventional doxorubicin and other available
      chemotherapy agents. 

PMID- 24018471
TI  - Consistency in reference radiotherapy dosimetry: resolution of an apparent
      conundrum when (60)Co is the reference quality for charged-particle and photon
      beams.
AB  - Substantial changes in ion chamber perturbation correction factors in (60)Co
      gamma-rays, suggested by recent Monte Carlo (MC) calculations, would cause a
      decrease of about 1.5% in the reference dosimetry of all types of charged
      particles (electrons, protons and heavier ions) based on calculated kQ values. It
      has gone largely unnoticed that the ratio of calibration coefficients ND, w, Co60
      and NK, air, Co60 yields an experimental value of Fch, Co60 = (sw-air pch)Co60
      through ND, air, Co60. Coefficients provided by the IAEA and traceable to the
      BIPM for 91 NE-2571 chambers result in an average Fch, Co60 which is compared
      with published (and new) MC simulations and with the value in IAEA TRS-398. It is
      shown that TRS-398 agrees within 0.12% with the experimental Fch, Co60. The 1.5%
      difference resulting from MC calculations (1.1% for the new simulations) cannot
      be justified using current fundamental data and BIPM standards if consistency in
      the entire dosimetry chain is sought. For photons, MC kQ factors are compared
      with TRS-398. Using the same uncertainty for Wair, the two sets of data overlap
      considerably. Experimental kQ values from standards laboratories lie between the
      two sets of calculated values, showing no preference for one set over the other.
      Observed chamber-to-chamber differences, that include the effect of waterproof
      sleeves (also seen for (60)Co), justify the recommendation in TRS-398 for kQ
      values specifically measured for the user chamber. Current developments on I
      values for the stopping powers of water and graphite are presented. A weighted
      average Iwater = 78 +/- 2 eV is obtained from published experimental and DRF
      based values; this would decrease sw-air for all types of radiotherapy beams
      between 0.3% and 0.6%, and would consequently decrease the MC derived Fch, Co60.
      The implications of a recent proposal for Igraphite = 81 eV are analysed,
      resulting in a potential decrease of 0.7% in NK, air, Co60 which would raise the
      experimental Fch, Co60; this would result in an increase of about 0.8% in the
      current TRS-398 value when referred to the BIPM standards. MC derived Fch, Co60
      using new stopping powers would then agree at a level of 0.1% with the
      experimental value, confirming the need for consistency in the dosimetry chain
      data. Should world average standards be used as reference, the figures would
      become +0.4% for TRS-398 and -0.3% for the MC calculation. Fch, Q calculated for
      megavoltage photons using new stopping powers would decrease by between 0.2% and
      0.5%. When they enter as a ratios in kQ, differences with MC values based on
      current key data would be within 0.2% but their discrepancy with kQ experimental
      photon values remains unresolved. For protons the new data would require an
      increase in Wair, Q of about 0.6%, as this is inferred from a combination of
      calorimetry and ionometry. This consistent scenario would leave unchanged the
      current TRS-398 kQ (NE-2571) data for protons, as well as for ions heavier than
      protons unless new independent Wair, Q values become available. Also in these
      advanced radiotherapy modalities, the need for maintaining data consistency in an
      analysis that unavoidably must include the complete dosimetry chain is
      demonstrated. 

PMID- 24018473
TI  - Clinical implications of genetic advances in Charcot-Marie-Tooth disease.
AB  - Charcot-Marie-Tooth disease (CMT) refers to a group of inherited neuropathies
      with a broad range of phenotypes, inheritance patterns and causative genes. The
      number of disease genes identified in CMT has expanded rapidly over the past few
      decades, such that more than 60 CMT-associated genes have now been discovered.
      This rise in genetic discovery can be attributed to the development of next
      generation sequencing (NGS) technology, which allows the entire exome or genome
      to be sequenced in a matter of days. In this Review, we discuss how NGS is being
      employed in the diagnostic evaluation of patients with CMT and how the genetic
      advances in CMT are influencing clinical practice. In particular, we explore how
      genetic advances have broadened the phenotype of CMT and related disorders and
      how NGS allows a large number of CMT genes to be screened simultaneously early in
      the evaluation of an unexplained neuropathy. Finally, we discuss the different
      methods of NGS that can be used in CMT and related disorders, and propose a
      simple diagnostic algorithm in which clinical assessment and neurophysiology are
      used to guide the application of phenotype specific 'panels'. 

PMID- 24018476
TI  - Genetics: RNA topoisomerase involved in neurodevelopmental disorders.

PMID- 24018477
TI  - Neurodegenerative disease: PDK1--a common therapeutic target for AD and prion
      disease?

PMID- 24018478
TI  - Stroke: a new CHANCE for combination antiplatelet therapy?
AB  - Patients with transient ischaemic attack or minor ischaemic stroke have a high
      risk of early recurrence. A new study in Chinese patients suggests that this risk
      is reduced following treatment with clopidogrel plus aspirin compared with
      aspirin alone. However, whether the findings can be extrapolated to other
      populations remains unclear.

PMID- 24018480
TI  - Spinal cord injury: Visualizing plasticity and repair in the injured CNS.
AB  - The heterogeneity of traumatic spinal cord injury necessitates large clinical
      trials to differentiate natural improvements from enhanced recovery due to
      therapeutic intervention. Recent development of an imaging biomarker to visualize
      changes in the corticospinal motor system could offer the opportunity to directly
      visualize anatomical evidence of repair, regeneration and plasticity.

PMID- 24018482
TI  - TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3+ Treg
      cells.
AB  - The innate Toll-like receptor 7 (TLR7) detects infections by recognizing viral
      and bacterial single-stranded RNA. In addition to pathogen-derived RNA, immune
      cells expressing high levels of TLR7, such as B cells and dendritic cells (DCs),
      can be activated by self-RNA. During myelin-induced experimental autoimmune
      encephalomyelitis (EAE), an animal model of multiple sclerosis, TLR7 expression
      is increased within the central nervous system (CNS). To define the contribution
      of TLR7 to the development of EAE, we evaluated the course of the disease in
      C57BL/6-Tlr7-deficient mice compared with that in WT mice and found that TLR7
      deficient mice had decreased disease severity. This protection was associated
      with decreased myelin oligodendrocyte glycoprotein-specific T-cell activation by
      primed DCs, decreased circulating autoantibodies, attenuated inflammation within
      the CNS, and increased Foxp3(+) regulatory T cells in the periphery and in the
      CNS. In conclusion, we show that TLR7 is involved in the maintenance of
      autoimmunity in the pathogenesis of EAE. 

PMID- 24018479
TI  - Reappraising neuropathic pain in humans--how symptoms help disclose mechanisms.
AB  - Neuropathic pain--that is, pain arising directly from a lesion or disease that
      affects the somatosensory system--is a common clinical problem, and typically
      causes patients intense distress. Patients with neuropathic pain have sensory
      abnormalities on clinical examination and experience pain of diverse types, some
      spontaneous and others provoked. Spontaneous pain typically manifests as ongoing
      burning pain or paroxysmal electric shock-like sensations. Provoked pain includes
      pain induced by various stimuli or even gentle brushing (dynamic mechanical
      allodynia). Recent clinical and neurophysiological studies suggest that the
      various pain types arise through distinct pathophysiological mechanisms. Ongoing
      burning pain primarily reflects spontaneous hyperactivity in nociceptive-fibre
      pathways, originating from 'irritable' nociceptors, regenerating nerve sprouts or
      denervated central neurons. Paroxysmal sensations can be caused by several
      mechanisms; for example, electric shock-like sensations probably arise from high
      frequency bursts generated in demyelinated non-nociceptive Abeta fibres. Most
      human and animal findings suggest that brush-evoked allodynia originates from
      Abeta fibres projecting onto previously sensitized nociceptive neurons in the
      dorsal horn, with additional contributions from plastic changes in the brainstem
      and thalamus. Here, we propose that the emerging mechanism-based approach to the
      study of neuropathic pain might aid the tailoring of therapy to the individual
      patient, and could be useful for drug development.

PMID- 24018483
TI  - Enhanced catalytic activity in organic solvents using molecularly dispersed
      haemoglobin-polymer surfactant constructs.
AB  - The surface of haemoglobin (Hb) is chemically modified to produce molecular
      dispersions of discrete core-shell Hb-polymer surfactant bionanoconjugates in
      water and organic solvents. The hybrid nanoconstructs exhibit peroxidase-like
      catalytic activity with enhanced turnover rates compared with native Hb in water.

PMID- 24018484
TI  - Microbiomic signatures of psoriasis: feasibility and methodology comparison.
AB  - Psoriasis is a common chronic inflammatory disease of the skin. We sought to use
      bacterial community abundance data to assess the feasibility of developing
      multivariate molecular signatures for differentiation of cutaneous psoriatic
      lesions, clinically unaffected contralateral skin from psoriatic patients, and
      similar cutaneous loci in matched healthy control subjects. Using 16S rRNA high
      throughput DNA sequencing, we assayed the cutaneous microbiome for 51 such
      matched specimen triplets including subjects of both genders, different age
      groups, ethnicities and multiple body sites. None of the subjects had recently
      received relevant treatments or antibiotics. We found that molecular signatures
      for the diagnosis of psoriasis result in significant accuracy ranging from 0.75
      to 0.89 AUC, depending on the classification task. We also found a significant
      effect of DNA sequencing and downstream analysis protocols on the accuracy of
      molecular signatures. Our results demonstrate that it is feasible to develop
      accurate molecular signatures for the diagnosis of psoriasis from microbiomic
      data. 

PMID- 24018485
TI  - Ultrafast electron and energy transfer in dye-sensitized iron oxide and
      oxyhydroxide nanoparticles.
AB  - An emerging area in chemical science is the study of solid-phase redox reactions
      using ultrafast time-resolved spectroscopy. We have used molecules of the
      photoactive dye 2',7'-dichlorofluorescein (DCF) anchored to the surface of
      iron(III) oxide nanoparticles to create iron(II) surface atoms via photo
      initiated interfacial electron transfer. This approach enables time-resolved
      study of the fate and mobility of electrons within the solid phase. However,
      complete analysis of the ultrafast processes following dye photoexcitation of the
      sensitized iron(III) oxide nanoparticles has not been reported. We addressed this
      topic by performing femtosecond transient absorption (TA) measurements of aqueous
      suspensions of uncoated and DCF-sensitized iron oxide and oxyhydroxide
      nanoparticles, and an aqueous iron(III)-dye complex. Following light absorption,
      excited state relaxation times of the dye of 115-310 fs were found for all
      samples. Comparison between TA dynamics on uncoated and dye-sensitized hematite
      nanoparticles revealed the dye de-excitation pathway to consist of a competition
      between electron and energy transfer to the nanoparticles. We analyzed the TA
      data for hematite nanoparticles using a four-state model of the dye-sensitized
      system, finding electron and energy transfer to occur on the same ultrafast
      timescale. The interfacial electron transfer rates for iron oxides are very close
      to those previously reported for DCF-sensitized titanium dioxide (for which dye
      oxide energy transfer is energetically forbidden) even though the acceptor states
      are different. Comparison of the alignment of the excited states of the dye and
      the unoccupied states of these oxides showed that the dye injects into acceptor
      states of different symmetry (Ti t2gvs. Fe eg).

PMID- 24018486
TI  - Ethyl gallate attenuates acute lung injury through Nrf2 signaling.
AB  - Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) is the
      clinical syndrome of persistent lung inflammation caused by various direct and
      indirect stimuli. Despite advances in the understanding of disease pathogenesis,
      few therapeutic have emerged for ALI/ARDS. Thus, in the present study we
      evaluated the therapeutic potential of ethyl gallate (EG), a plant flavanoid in
      the context of ALI using in vivo (BALB/c) and in vitro models (human monocytes).
      Our in vivo data supports the view that EG alleviates inflammatory condition in
      ALI as significant reduction in BALF neutrophils, ROS, proinflammatory cytokines
      and albumin levels were observed with the single i.p of EG post LPS exposure.
      Also, histochemical analysis of mice lung tissue demonstrated that EG restored
      LPS stimulated cellular influx inside the lung airspaces. Unraveling the
      mechanism of action, our RT-PCR and western blot analysis suggest that enhanced
      expression of HO-1 underlies the protective effect of EG on ROS level in mice
      lung tissue. Induction of HO-1 in turn appears to be mediated by Nrf2 nuclear
      translocation and consequent activation and ablation of Nrf2 activity through
      siRNA notably abrogated the EG induced protective effect in LPS induced human
      monocytes. Furthermore, our results indicate that EG generated moderate amounts
      of H2O2 could induce Nrf2 translocation in the in vitro systems. However, given
      the insignificant amount of H2O2 recorded in the injected material in the in vivo
      system, additional mechanism for EG action could not be excluded. Nevertheless
      our results highlight the protective role of EG in ALI and provide the novel
      insight into its usefulness as a therapeutic tool for the treatment of ALI.

PMID- 24018489
TI  - Coagulation abnormalities in the cirrhotic patient.
AB  - The clotting process is a dynamic array of multiple processes which can be
      described in four phases: platelet plug initiation and formation, clotting
      process propagation by the coagulation cascade, clotting termination by
      antithrombotic mechanisms and clot removal by fibrinolysis. The liver plays a
      central role in each of these phases of clotting process, as it synthesizes the
      majority of coagulation factors and proteins involved in fibrinolysis as well as
      thrombopoeitin, which is responsible for platelet production from megakaryocytes.
      Many pathological processes associated with cirrhosis, such as portal
      hypertension and endothelial dysfunction, as well as co-morbid conditions, may
      also alter the coagulation process. Consequently, patients with liver disease
      have a disturbed balance of procoagulant and anti-coagulant factors which
      deviates from the normal coagulation cascade. This situation poses an additional
      problem in the diagnostic and therapeutic approach to this group of patients,
      since traditional coagulation test may not be reliable for assessing bleeding or
      thrombotic risk and traditional transfusional strategies may not be applicable in
      cirrhotic patients. In this article, we review the pathophysiological bases of
      coagulation abnormalities, in cirrhotic patients, the diagnostic therapeutic
      strategies to be followed and its impact on the clinical outcome in the cirrhotic
      patient. 

PMID- 24018490
TI  - Use of proteomic analysis tools to identify HCV-proteins down-regulated by
      acetylsalicylic acid.
AB  - Background and aim. Acetylsalicylic acid (ASA) has been shown to downregulate HCV
      expression; however, the involved mechanisms are unknown. We used proteomic
      analysis to compare protein expression profiles between human hepatocarcinoma
      cells (Huh7) and Huh7-HCV cells harboring expression of non-structural HCV
      proteins, to elucidate the mechanism(s) involved in ASA-mediated downregulation
      of HCV replication. Material and methods. Both cell lines were treated or
      untreated with 4 mM ASA and harvested at 0, 24, 48 and 72 h to isolate total
      proteins, which were resolved by two-dimensional gel electrophoresis (2DE) to
      separate them by isoelectric point (pI), followed by fractionation by molecular
      weight (MW). Gels were scanned and analyzed with PD-Quest software V8.0.1, and
      proteins were elucidated by the specific pI and MW using TAGIDENT software.
      Statistics analysis included the t-test. esults and Discussion. Different protein
      patterns among hepatocytes expressing HCV-proteins in ASA treated and untreated
      cells were found. Among proteins differentially expressed in Huh7-HCV cells, we
      found proteins related to cell proliferation (MTMR6, FAM22, HDGF and HCF-1) after
      24 h of ASA treatment; and upregulation of angiostatin, PI4KA and STAT-1 after 48
      h of treatment. Finally, at 72 h of ASA exposure, we identified overexpression of
      adenylsuccinate synthase, 2'-3'-di-deoxyadenosine, ubiquitin-protein-ligase E6A,
      adenylosuccinate-lyase and nibrin (NBN). Conclusion. We found that ASA induces
      different protein patterns in Huh7-HCV cells promoting activation of proteins
      involved in cell progression, repair of double strand breaks, proliferation,
      inhibition of apoptosis and growth stimulation at the same time that it decreased
      HCV expression. 

PMID- 24018491
TI  - The X-ray repair cross complementing protein 1 (XRCC1) rs25487 polymorphism and
      susceptibility to cirrhosis in Brazilian patients with chronic viral hepatitis.
AB  - INTRODUCTION: The progression of hepatic disease in chronic viral hepatitis is
      accompanied by an increased production of reactive oxygen species (ROS), as well
      as an accumulation of oxidative DNA damage, which is primarily repaired through
      base excision repair. XRCC1 (X-ray repair cross complementing protein 1) is one
      of the most important proteins involved in this repair pathway. The present study
      was carried out to verify the possible association of the XRCC1 rs25487
      polymorphism with cirrhosis in patients from Central-West Brazil. MATERIAL AND
      METHODS: A total of 227 individuals with viral hepatitis, 53 cirrhotic and 174
      non-cirrhotic, were genotyped for the XRCC1 rs25487 polymorphism using PCR-RFLP.
      RESULTS: There were significantly higher frequencies of both the Arg/Gln genotype
      and of individuals with at least one Gln allele (Arg/ Gln+Gln/Gln) among
      cirrhotic patients (56.6% and 69.8%) compared with non-cirrhotic patients (25.8%
      and 37.9%). Both conditions were significantly associated with cirrhosis,
      independent of age, sex, alcohol intake or tobacco use (adjusted OR = 3.5, CI =
      1.7-7.4, p = 0.001 and adjusted OR = 3.1, CI = 1.5-6.3, p = 0.002, respectively).
      Similar results were obtained for a group of HCV-infected patients but not for
      HBV-infected patients. CONCLUSIONS: The XRCC1 rs25487 polymorphism may influence
      the development of cirrhosis in viral hepatitis patients, and additional
      investigation will be necessary.

PMID- 24018492
TI  - Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV-
      infected patients.
AB  - BACKGROUND: Conflicting data have been reported on the prevalence of liver
      steatosis, its risk factors and its relationship with fibrosis in patients with
      human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with
      HCV mono-infection. AIM: The study aims were to assess steatosis prevalence and
      its risk factors in both HCV groups. We also evaluated whether steatosis was
      linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono
      infected patients were consecutively enrolled. They underwent liver
      ultrasonography and transient elastography. Bright liver echo-pattern was used to
      diagnose steatosis; advanced fibrosis was defined as liver stiffness >= 9.5 kPa
      and FIB-4 values >= 3.25. The optimal stiffness cut-off according to FIB-4 >=
      3.25 was evaluated by ROC analysis. RESULTS: No significant difference was found
      in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%).
      Steatosis was associated with triglycerides and impaired fasting glucose/diabetes
      in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol
      and triglycerides in co-infected patients. Stiffness >= 9.5 was significantly
      more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly
      associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79
      0.9). On multivariate analysis steatosis was associated with triglycerides in
      both HCV mono- and co-infected groups (P < 0.02; P < 0.03). CONCLUSION: Although
      steatosis was common in both HCV mono- and co-infected patients, it was not
      linked with advanced fibrosis. Triglycerides were independent predictors of
      steatosis in either of the HCV-groups. Dietary interventions and lifestyle
      changes should be proposed to prevent metabolic risk factors.

PMID- 24018493
TI  - Primary care practitioners survey of non-alcoholic fatty liver disease.
AB  - BACKGROUND: The rising incidence of non alcoholic fatty liver disease (NAFLD)
      mirrors the epidemics of obesity and metabolic syndrome. Primary care
      practitioners (PCPs) are central to management of patients with NAFLD, but data
      on knowledge and attitudes of PCPs towards NAFLD are lacking. MATERIAL AND
      METHODS: We conducted a statewide, stratified survey of 250 PCPs to examine
      knowledge, practices and attitudes regarding NAFLD and the barriers to providing
      care for this condition. RESULTS: NAFLD was perceived as an important health
      problem by 83% of PCPs. Eighty five percent of PCPs underestimated the population
      prevalence of NAFLD. Although the association of NAFLD with metabolic syndrome
      was identified by 91% of PCPs, only 46% screened diabetic obese patients for
      NAFLD. Only 27% of PCPs referred NAFLD patients to a hepatologist for evaluation.
      PCPs who reported seeing more than 5 NAFLD patients annually, referred to
      hepatology less frequently (P = 0.01). The majority of PCPs (58%) recommended
      weight loss and a calorie restriction. Only 8% of PCPs would recommend Vitamin E.
      The major perceived barrier in managing NAFLD was lack of confidence in
      understanding of the disease (58% of PCPs). DISCUSSION: An overwhelming majority
      of PCPs perceived NAFLD as an important health issue in their practice. However,
      screening rates for NAFLD among obese diabetics were low. A major barrier to
      managing these patients was self-reported lack of knowledge about NAFLD.
      Development of guidelines should emphasize strategies for screening vulnerable
      populations (obese, diabetics), evidence based management and barriers to
      providing care.

PMID- 24018494
TI  - Imaging surveillance and multidisciplinary review improves curative therapy
      access and survival in HCC patients.
AB  - INTRODUCTION: Imaging surveillance and multidisciplinary conference (MDC) review
      can potentially improve survival in patients with hepatocellular carcinoma (HCC)
      by increasing access to liver transplantation. Geographic disparities in donor
      organ availability may reduce this benefit. This study evaluated the impact of
      HCC surveillance on use of curative therapies and survival in a region with long
      transplant waiting times. MATERIAL AND METHODS: 167 HCC patients were
      retrospectively studied. Subjects had an established HCC diagnosis or were
      diagnosed during hepatology follow-up. Collected data included patient
      demographics, HCC surveillance and MDC review status, portal hypertension
      complications, laboratory and radiologic parameters, tumor size, therapeutic
      interventions, tumor progression, and mortality. The primary outcome measures
      were use of curative treatments and survival. A Cox-regression model was
      constructed utilizing factors associated with survival in univariate analysis.
      RESULTS: 58% of subjects underwent surveillance and MDC review of HCC. These
      patients were more likely to have received treatment with ablation or resection
      (16 vs. 3%, P = 0.006) and transplantation (23 vs. 4%, P = 0.001), and were less
      likely to develop tumor progression (45 vs. 68%, P = 0.005) or metastases (0 vs.
      19%, P < 0.001). In multivariate analysis, surveillance and MDC review (P =
      0.034, HR 0.520, 95% CI 0.284-0.952), tumor meeting Milan criteria (P < 0.001, HR
      0.329, 95% CI 0.178-0.607), curative therapy application (P = 0.048, HR 0.130,
      95% CI 0.017-0.979), and transplantation (P = 0.004, HR 0.236, 95% CI 0.088
      0.632) were associated with survival. CONCLUSION: In conclusion, imaging
      surveillance and MDC review is associated with detection of early stage HCC,
      increased access to curative therapies and transplantation, and prolonged
      survival.

PMID- 24018495
TI  - Caspase recruitment domains. New potential markers for diagnosis of
      hepatocellular carcinoma associated with HCV in Egyptian patients.
AB  - BACKGROUND AND RATIONALE FOR THE STUDY: Chronic HCV is a major cause of HCC
      development. Caspase Recruitment Domains (CARD) is protein modules that regulate
      apoptosis and play an important role in various carcinogenesis processes, our aim
      is to assess the possible role of CARD9, CARD10 and Caspase only protein (COP) in
      progression of liver fibrosis and pathogenesis of HCC in Egyptian chronic HCV
      patients. MATERIAL AND METHODS: 130 patients were recruited and classified into 4
      groups; I: chronic HCV, II: chronic active hepatitis, III: liver cirrhosis, IV:
      HCV related HCC. Biochemical, virological studies, abdominal ultrasonography and
      liver biopsy were performed. Quantitative estimation of mRNA of CARD9, CARD10 and
      COP gene expression was performed by RT- PCR in liver biopsy from all patients.
      RESULTS: In HCC patients; age, AFP and liver profile were significantly higher,
      HB and platelets were significantly lower (p value <0.01). The expression levels
      of mRNA of CARD9, CARD10 and COP in liver biopsies of HCC were significantly
      higher than other groups with direct correlation with age and no correlation with
      AFP, viral load, liver fibrosis or necroinflammatory activity. On differentiation
      between HCC and non HCC patients each CARD was assessed separately and combined,
      on combing the 3 CARDs, the sensitivity was 100%, specificity was 48%, positive
      predictive value 47% and negative predictive value 100%. CONCLUSIONS: CARD9,
      CARD10 and COP had no role in liver fibrosis but may be involved in hepatic
      carcinogenesis and they could be used as markers for HCC diagnosis and candid
      genes for molecular target therapy.

PMID- 24018496
TI  - Treatment of polycystic liver disease: a hypothesis, patient characteristics,
      short and long-term results.
AB  - BACKGROUND: Non-total liver resecting invasive treatment of polycystic liver
      disease has different recurrence rates. The aim of this study is to illustrate
      why the recurrence rates are different. We established a hypothesis that the cyst
      number is a constant in polycystic liver disease in a patient's lifetime.
      MATERIAL AND METHODS: We selected 287 patients with polycystic liver, in which 35
      patients had the record of liver volume, while other 252 patients had the record
      of length of right liver. Data were divided into 5 groups in terms of age. The
      intergroup comparison with different ages and clinical files of patients were
      analyzed. RESULTS: The mean difference was statistically insignificant when
      compared amongst groups in the lengths of right liver respectively. Symptom
      recurrence rates (q) were 19.05 and 17.65% respectively after cyst aspiration
      sclerotherapy and non-cyst aspiration-sclerotherapy. CONCLUSION: The cyst number
      is a constant in patients with non-massive or massive polycystic liver disease in
      their lifetime.

PMID- 24018498
TI  - Within-patient temporal variance in MELD score and impact on survival prediction
      after TIPS creation.
AB  - BACKGROUND: To assess within-patient temporal variability in Model for End Stage
      Liver Disease (MELD) scores and impact on outcome prognostication after
      transjugular intrahepatic portosystemic shunt (TIPS) creation. MATERIAL AND
      METHODS: In this single institution retrospective study, MELD score was
      calculated in 68 patients (M:F = 42:26, mean age 55 years) at 4 pre-procedure
      time points (1, 2-6, 7-14, and 15-35 days) before TIPS creation. Medical record
      review was used to identify 30- and 90-day clinical outcomes. Within-patient
      variability in pre-procedure MELD scores was assessed using repeated measures
      analysis of variance, and the ability of MELD scores at different time points to
      predict post-TIPS mortality was evaluated by comparing area under receiver
      operating characteristic (AUROC) curves. RESULTS: TIPS were successfully created
      for ascites (n = 30), variceal hemorrhage (n = 29), hepatic hydrothorax (n = 8),
      and portal vein thrombosis (n = 1). Pre-TIPS MELD scores showed significant (P =
      0.032) within-subject variance that approached +/- 18.5%. Higher MELD scores
      demonstrated greater variability in sequential scores as compared to lower MELD
      scores. Overall 30- and 90-day patient mortality was 22% (15/67) and 38% (24/64).
      AUROC curves showed that most recent MELD scores performed on the day of TIPS had
      superior predictive capacity for 30- (0.876, P = 0.037) and 90-day (0.805 P =
      0.020) mortality compared to MELD scores performed 2-6 or 7-14 days prior.
      CONCLUSIONS: In conclusion, MELD scores show within-patient variability over
      time, and scores calculated on the day of TIPS most accurately predict risk and
      should be used for patient selection and counseling.

PMID- 24018497
TI  - Acute liver failure in under two year-olds--are there markers of metabolic
      disease on admission?
AB  - INTRODUCTION: The early establishment of an etiology for acute liver failure
      (ALF) in infants is essential for the start of adequate treatment in the shortest
      timeframe possible. AIM: To identify markers of inherited metabolic disease on
      admission in children under two years of age with ALF. MATERIAL AND METHODS: A
      retrospective review of the medical records of all children (< 2 years old) with
      ALF admitted to the pediatric hepatology or intensive care units of a tertiary
      center over a twenty-three year period (January 1989 to December 2011) was done.
      Patients were divided into two groups: with (group A) or without (group B) a
      metabolic etiology. Clinical and laboratory parameters on admission were
      compared. RESULTS: Twenty-three children met inclusion criteria. Twelve had ALF
      of metabolic origin (group A). The median age in this group was 2.25 (Q1-Q3: 0.63
      4.65) months and in group B 8.0 (Q1-Q3: 1.5-15) months. History of failure to
      thrive and/or vomiting was more frequent in group A (p = 0.022). Age, gender,
      encephalopathy and left ventricular hypertrophy were similar in both groups (p =
      0.147, p = 1.000, p = 0.637, p = 1.000, respectively). Laboratory tests on
      admission (plasma lactate, ammonia, cholesterol, phosphate, INR, glucose,
      bilirubin, ALT, base excess and the presence of reducing substances in urine)
      showed no statistically significant differences between groups. CONCLUSION: This
      study showed that although infants with inborn errors of metabolism showed a
      trend towards lower age at presentation, the only marker of inherited metabolic
      disease found on admission was history of vomiting and/or failure to thrive.

PMID- 24018499
TI  - Oral acetyl-L-carnitine treatment in hepatic encephalopathy: view of evidence
      based medicine.
AB  - OBJECTIVE: To systematically review the effect of acetyl-L-carnitine in patients
      with hepatic encephalopathy. MATERIAL AND METHODS:  DESIGN: systematic review and
      meta-analysis. DATA SOURCES: The Cochrane Library, MEDLINE, EMBASE.com, Science
      Citation Index, Google search and the China Biological Medicine Database to June
      2012. REVIEW METHODS: randomized placebo controlled trials of acetyl-L-carnitine
      in patients with hepatic encephalopathy assessing whether acetyl-L-carnitine is
      an effective therapy or not. No language restrictions were applied. Two reviewers
      independently extracted data and assessed quality. RESULTS: 7 methodologically
      sound randomized controlled trials were identified involving 660 participants
      with hepatic encephalopathy, totaling 249 with subclinical hepatic
      encephalopathy, 189 with West Haven grade 1, 162 with West Haven grade 2 and 60
      with West Haven grade 3. Acetyl-L-carnitine was effective to improve serum
      ammonia level (weighted mean difference 25.90, 95% confidence intervals 20.89 to
      30.91, P < 0.05) and the number connection test completion time (weighted mean
      difference 16.62, 95% confidence intervals 9.88 to 23.36, P < 0.05). The outcome
      was consistent in subgroup analyses. No publication bias was detected. Adverse
      events were reported infrequently and were minor. CONCLUSIONS: Acetyl-L-carnitine
      is promising as an effective and tolerable treatment for hepatic encephalopathy
      that associated with improved serum ammonia levels and the number connection
      test.

PMID- 24018500
TI  - Aspartate aminotransferase-to-platelet ratio index (APRI) for the non-invasive
      prediction of esophageal varices.
AB  - BACKGROUND & AIMS: Variceal bleeding is a dramatic and common complication of
      cirrhosis, and, therefore, endoscopy is recommended for the screening of EV
      (esophageal varices) in every cirrhotic. This study evaluates the capacity of
      APRI (aspartate aminotransferase-to-platelet ratio index) in non-invasively
      predicting EV. MATERIAL AND METHODS: This cross-sectional study evaluated
      cirrhotics for their APRI value and the presence of EV, with a cutoff point of 1,
      3; platelet count, spleen diameter, PC/SD (platelet count/ spleen diameter
      ratio), aspartate aminotransferase/alanine aminotransferase ratio, Child-Pugh
      score and MELD (model for end-stage liver disease) score were also studied.
      RESULTS: The study included 164 cirrhotics, 59.7% male, with a mean age of 56.7
      years. APRI demonstrated a sensitivity of 64.7% (95% confidence interval-95%CI =
      0.56-0.73), specificity of 72.7% (95%CI = 0.59-0.86), positive predictive value
      of 86.5% (95%CI = 0.79-0.94), negative predictive value of 43.2% (95%CI = 0.32
      0.55). In the univariate analysis, platelet count, spleen diameter, Child and
      MELD scores, PC/SD and APRI were related to EV (p < 0.05). In the logistic
      regression, only platelet count and Child score were associated to EV (p < 0.05).
      CONCLUSION: APRI is not an independent factor for the prediction of EV. Its
      sensitivity, specificity and predictive values are insufficient for the index to
      be used for the screening of EV in cirrhotics.

PMID- 24018501
TI  - Notch signal protects non-parenchymal cells from ischemia/reperfusion injury in
      vitro by repressing ROS.
AB  - BACKGROUND: We have previously reported that Notch signaling pathway protects
      hepatocytes from ischemia/ reperfusion (I/R) injury by repressing reactive oxygen
      species (ROS) production. However, apart from hepatocytes, non-parenchymal cells
      including vascular endothelia cells, Kupffer cells and hepatic stellate cells are
      also reported to be involved in hepatic I/R injury. AIM: To clarify the role of
      Notch signaling in non-parenchymal cells subjected to I/R injury. MATERIALS AND
      METHODS: Human Umbilical Vein Endothelial Cells (HUVECs), mouse macrophage line
      RAW264.7 and rat hepatic stellate cell line HSC-T6 were cultured and subjected to
      I/R injury, respectively. Activation of Notch signaling was assessed by NICD
      western blot. Then, pharmacological inhibitor (gamma-secretase inhibitor GSI) was
      used to block Notch signaling of related cell lines in vitro. Intracellular ROS
      was detected and analyzed by FACS and apoptosis was examined by TUNEL staining
      and Annexin V staining. RESULTS: Notch signaling responded to I/R injury and I/R
      injury induced activation of Notch signaling in nonparenchymal cells. Notch
      signal deficiency led to overproduction of ROS and aggravated cell death of non
      parenchymal cells subjected to I/R injury. CONCLUSION: Notch signal protects non
      parenchymal cells from I/R injury by repressing ROS.

PMID- 24018502
TI  - A giant calcified hepatic mass.

PMID- 24018503
TI  - Hepatocellular carcinoma that arose from primary Sjogren's syndrome.
AB  - Hepatocellular carcinoma (HCC) typically originates from HBV or HCV associated
      liver cirrhosis. Primary Sjogren's syndrome (pSS) is a kind of autoimmune
      disease. A sixty-two year old female patient with mild liver damage was diagnosed
      with pSS after excluding viral, alcoholic and drug-induced hepatitis according to
      serum immunological detection and liver biopsy. But when she was hospitalized for
      a second time two years later, a CT scan revealed liver neoplasm. Surgery
      confirmed HCC and liver cirrhosis by pathology. The elevated level of AFP
      recovered to normal after tumorectomy. In conclusion, HCC might be a candidate
      outcome in patients with pSS; it is the doctors' responsibility to keep this kind
      of patient under surveillance. 

PMID- 24018504
TI  - Rhombencephalitis by Listeria monocytogenes in a cirrhotic patient: a case report
      and literature review.
AB  - We report a case of rhombencephalitis infection by Listeria monocytogenes in a 66
      year-old man with cirrhosis. The CSF analysis indicated L. monocytogenes as the
      most likely pathogen. Blood and CSF culture were positive to L. monocytogenes and
      MRI findings were suggestive of rhomboencephalitis. The treatment was started
      empirically and then modified when the culture results were available. The
      patient had a full clinical recovery without neurologic sequelae. Clinicians
      should remember that L. monocytogenes most often presents as acute bacterial
      meningitis, particularly in the elderly, the immunosuppressed, and those with
      malignancies. L. monocytogenes CNS the infections may present as acute bacterial
      meningitis, meningoencephalitis, or acute encephalitis. 

PMID- 24018505
TI  - Subacute liver failure by pseudocirrhotic metastatic breast cancer infiltration.
AB  - Hepatic metastases are common in the clinical course of breast cancer and
      typically appear as mass lesions. This report describes the case of a 70-year-old
      woman with a history of breast cancer and no previously known liver disease
      presenting with the first episode of variceal bleeding and subacute hepatic
      failure. Imaging studies indicated liver cirrhosis without signs of malignant
      focal lesions. Comprehensive diagnostic work-up was negative for specific causes
      of liver disease and provided no evidence for tumor recurrence. Finally
      transjugular liver biopsy revealed a marked diffuse desmoplastic infiltration by
      breast cancer cells. Malignant pseudocirrhosis is an unusual pattern of
      metastatic, tumor spread representing a rare but important differential diagnosis
      of progressive liver failure. Liver biopsy is the key procedure to establish the
      diagnosis as imaging studies may mimic cirrhosis. 

PMID- 24018506
TI  - Syncope during boceprevir treatment in hepatitis C.

PMID- 24018507
TI  - Liver stiffness measurements increase after meal ingestion--an important step
      towards standardization.

PMID- 24018509
TI  - National healthcare systems and the need for health information governance.
AB  - This chapter gives an overview of health data, information and knowledge
      governance needs and associated generic principles so that information systems
      are able to automate such data collections from point-of-care operational
      systems. Also covered are health information systems' dimensions and known
      barriers to the delivery of quality health services, including environmental,
      technology and governance influences of any population's health status within the
      context of national health systems. This is where health information managers and
      health informaticians need to resolve the many challenges associated with eHealth
      implementations where data are assets, efficient information flow is essential,
      the ability to acquire new knowledge desirable, and where the use of data and
      information needs to be viewed from a governance perspective to ensure reliable
      and quality information is obtained to enhance decision making. 

PMID- 24018510
TI  - Impact of data governance on a nation's healthcare system building blocks.
AB  - This chapter gives an overview of a nation's healthcare system, particularly for
      those who are familiar with IT but not healthcare or for those working in one
      area of healthcare who may not be familiar with the system and data requirements
      across the care continuum. The structure of this chapter uses the World Health
      Organisation's (WHO) Health systems framework with a focus on the need for data
      and information governance to achieve a sustainable health system delivering
      improved health for all, responsively and equitably meeting genuine demands for
      health services, with social and financial risk protection and overall improved
      efficiency. It is argued that there is a need to gather the right data and to
      process these data in a manner that provides good information in order to more
      fully understand how the health system is working and where and when it isn't
      working well. This needs to be achieved in the most cost effective manner that
      doesn't detract from the allocation of resources to healthcare or the clinical
      workflow required to achieve quality healthcare. 

PMID- 24018511
TI  - Health data and data governance.
AB  - Health is a knowledge industry, based on data collected to support care, service
      planning, financing and knowledge advancement. Increasingly there is a need to
      collect, retrieve and use health record information in an electronic format to
      provide greater flexibility, as this enables retrieval and display of data in
      multiple locations and formats irrespective of where the data were collected.
      Electronically maintained records require greater structure and consistency to
      achieve this. The use of data held in records generated in real time in clinical
      systems also has the potential to reduce the time it takes to gain knowledge, as
      there is less need to collect research specific information, this is only
      possible if data governance principles are applied. Connected devices and
      information systems are now generating huge amounts of data, as never before
      seen. An ability to analyse and mine very large amounts of data, "Big Data",
      provides policy and decision makers with new insights into varied aspects of work
      and information flow and operational business patterns and trends, and drives
      greater efficiencies, and safer and more effective health care. This enables
      decision makers to apply rules and guidance that have been developed based upon
      knowledge from many individual patient records through recognition of triggers
      based upon that knowledge. In clinical decision support systems information about
      the individual is compared to rules based upon knowledge gained from accumulated
      information of many to provide guidance at appropriate times in the clinical
      process. To achieve this the data in the individual system, and the knowledge
      rules must be represented in a compatible and consistent manner. This chapter
      describes data attributes; explains the difference between data and information;
      outlines the requirements for quality data; shows the relevance of health data
      standards; and describes how data governance impacts representation of content in
      systems and the use of that information. 

PMID- 24018512
TI  - Our health language and data collections.
AB  - All communication within the health industry is dependent upon the use of our
      health language consisting of a very extensive and complex vocabulary. Converting
      this language into computable formats is necessary in a digital environment with
      a strong reliance on data, information and knowledge sharing. This chapter
      describes our health language, what terminologies and ontologies are, their use
      and relationships with natural language, indexing, data standards, data
      collections and the need for data governance. 

PMID- 24018513
TI  - Data governance frameworks and change management.
AB  - Protecting and preserving data stored in electronic form is important, and
      ensuring that data is available to the correct access level requires
      consideration of the characteristics of the data and the purpose to which the
      data will be used. Important questions therefore are raised about what is the
      right data and who has the right access level. This is the substance of data
      governance. This paper will discuss the various aspects of data governance
      frameworks as it pertains to health care systems. The paper will also explore the
      changes that confront organisations and individuals as they embrace the
      requirements of data governance. 

PMID- 24018514
TI  - Health information systems.
AB  - Health information provides the foundation for all decision making in healthcare
      whether clinical at the bed side, or at a national government level. This
      information is generally collected as part of systems which support
      administrative or clinical workflow and practice. This chapter describes the many
      and varied features of systems such as electronic health records (EHRs), how they
      fit with health information systems and how they collectively manage information
      flow. Systems engineering methods and tools are described together with their use
      to suit the health industry. This focuses on the need for suitable system
      architectures and semantic interoperability. These concepts and their relevance
      to the health industry are explained. The relationship and requirements for
      appropriate data governance in these systems is also considered. 

PMID- 24018515
TI  - Health workforce competencies needed for a digital world.
AB  - The health workforce constitutes a very significant health system building block.
      As such it needs to have the capacity to influence how health data are captured,
      processed and used at all levels of decision making. This requires a national
      strategy that ensures all new health professional graduates are adequately
      prepared and that the existing workforce is developed to make the best possible
      use of all available digital technologies. This chapter provides an argument for
      why and how the health workforce should be contributing to health information
      governance, followed by an historical overview of various initiatives undertaken,
      the results achieved and issues identified during these processes. It concludes
      with an exploration of strategies that may be adopted to bring about change and
      achieve improvements. 

PMID- 24018516
TI  - The health informatics professions.
AB  - This chapter identifies the skills, professional challenges and changes needed
      for health and IT workforce development, to support a team based integrated
      approach to the development and implementation of successful, cost effective,
      safe systems in healthcare. This requires an attitude which embraces change and
      breaks down existing hierarchical structures and responsibilities by recognising
      the need for different and extended knowledge and skills within each professional
      area and within any organisational workforce composition. 

PMID- 24018517
TI  - Information security governance: a risk assessment approach to health information
      systems protection.
AB  - It is no small task to manage the protection of healthcare data and healthcare
      information systems. In an environment that is demanding adaptation to change for
      all information collection, storage and retrieval systems, including those for of
      e-health and information systems, it is imperative that good information security
      governance is in place. This includes understanding and meeting legislative and
      regulatory requirements. This chapter provides three models to educate and guide
      organisations in this complex area, and to simplify the process of information
      security governance and ensure appropriate and effective measures are put in
      place. The approach is risk based, adapted and contextualized for healthcare. In
      addition, specific considerations of the impact of cloud services, secondary use
      of data, big data and mobile health are discussed. 

PMID- 24018519
TI  - Organising and presenting information.
AB  - Information management can be a daunting process for clinicians, health care
      providers and policy makers within the health care industry. This chapter
      discusses the importance of information classification and information
      architecture in the information economy and specific challenges faced within the
      health care industry. The healthcare sector has industry specific requirements
      for information management, standards and specifications for information
      presentation. Classification of information based on information criticality and
      the value in the health care industry is discussed in this paper. Presentation of
      information with reference to eHealth standards and specifications for healthcare
      information systems and their key requirements are also discussed, as are
      information architecture for eHealth implementation in Australia. This chapter
      also touches on information management and clinical governance since the
      importance of information governance is discussed by various researchers and how
      this is becoming of value to healthcare information management. 

PMID- 24018520
TI  - Clinical professional governance for detailed clinical models.
AB  - This chapter describes the need for Detailed Clinical Models for contemporary
      Electronic Health Systems, data exchange and data reuse. It starts with an
      explanation of the components related to Detailed Clinical Models with a brief
      summary of knowledge representation, including terminologies representing clinic
      relevant "things" in the real world, and information models that abstract these
      in order to let computers process data about these things. Next, Detailed
      Clinical Models are defined and their purpose is described. It builds on existing
      developments around the world and accumulates in current work to create a
      technical specification at the level of the International Standards Organization.
      The core components of properly expressed Detailed Clinical Models are
      illustrated, including clinical knowledge and context, data element
      specification, code bindings to terminologies and meta-information about authors,
      versioning among others. Detailed Clinical Models to date are heavily based on
      user requirements and specify the conceptual and logical levels of modelling. It
      is not precise enough for specific implementations, which requires an additional
      step. However, this allows Detailed Clinical Models to serve as specifications
      for many different kinds of implementations. Examples of Detailed Clinical Models
      are presented both in text and in Unified Modelling Language. Detailed Clinical
      Models can be positioned in health information architectures, where they serve at
      the most detailed granular level. The chapter ends with examples of projects that
      create and deploy Detailed Clinical Models. All have in common that they can
      often reuse materials from earlier projects, and that strict governance of these
      models is essential to use them safely in health care information and
      communication technology. Clinical validation is one point of such governance,
      and model testing another. The Plan Do Check Act cycle can be applied for
      governance of Detailed Clinical Models. Finally, collections of clinical models
      do require a repository in which they can be stored, searched, and maintained.
      Governance of Detailed Clinical Models is required at local, national, and
      international levels. 

PMID- 24018521
TI  - Quality and safety of detailed clinical models.
AB  - This chapter describes quality and safety risks related to the development and
      use of Detailed Clinical Models (DCM) and mechanisms which may be employed to
      mitigate such risks. The chapter begins with a brief discussion of DCMs and the
      role they can play in mitigating patient safety risk. There is then a brief
      description of the risks which DCMs themselves may introduce, followed by the
      introduction of a standards-based risk assessment method and the ways this
      assessment method may be applied to DCMs in particular. A general description is
      then made of the ISO 9000-based approach to quality management systems (QMS) and,
      specifically, how such an approach may be applied to DCM development,
      maintenance, deployment and use. The chapter concludes with a discussion of
      specific DCM quality and safety challenges and governance approaches which may be
      employed to help address these. 

PMID- 24018522
TI  - Clinical knowledge governance: the international perspective.
AB  - As a basis for semantic interoperability, ideally, a Clinical Knowledge Resource
      for a clinical concept should be defined formally and defined once in a way that
      all clinical professions and all countries can agree on. Clinical Knowledge
      Governance is required to create high-quality, reusable Clinical Knowledge
      Resources and achieve this aim. Traditionally, this is a time-consuming and
      cumbersome process, relying heavily on face-to-face meetings and being able to
      get sufficient input from clinicians. However, in a national or even
      international space, it is required to streamline the processes involved in
      creating Clinical Knowledge Resources. For this, a Web 2.0 tool that supports
      online collaboration of clinicians during their creation and publishing of
      Clinical Knowledge Resources has been developed. This tool is named the Clinical
      Knowledge Manager (CKM) and supports the development, review and publication of
      Clinical Knowledge Resources. Also, post-publication activities such as adding
      terminology bindings, translating the Clinical Knowledge Resource into another
      language and republishing it are supported. The acceptance of Clinical Knowledge
      Resources depends on their quality and being able to determine their quality, for
      example it is important to know that a broad umber of reviewers from various
      clinical disciplines have been involved in the development of the Clinical
      Knowledge Resource. We are still far from realizing the vision of a global
      repository of a great number of reusable, high-quality Clinical Knowledge
      Resources, which can provide the basis for broad semantic interoperability
      between systems. However progress towards this aim is being made around the
      world. 

PMID- 24018523
TI  - Using a single content model for eHealth interoperability and secondary use.
AB  - This chapter describes a middle-out approach to eHealth interoperability, with
      strong oversight on public health and health research, enabled by a uniform and
      shared content model to which all health information exchange conforms. As
      described in New Zealand's Interoperability Reference Architecture, the content
      model borrows its top level organization from the Continuity of Care Record (CCR)
      standard and is underpinned by the openEHR formalism. This provides a canonical
      model for representing a variety of clinical information, and serves as reference
      when determining payload in health information exchange. The main premise of this
      approach is that since all exchanged data conforms to the same model,
      interoperability of clinical information can readily be achieved. Use of
      Archetypes ensures preservation of clinical context which is critical for
      secondary use. The content model is envisaged to grow incrementally by adding new
      or specialised archetypes as finer details are needed in real projects. The
      consistency and long term viability of this approach critically depends on
      effective governance which requires new models of collaboration, decision making
      and appropriate tooling to support the process. 

PMID- 24018525
TI  - Data governance for health care providers.
AB  - Data governance is characterised from broader definitions of governance. These
      characteristics are then mapped to a framework that provides a practical
      representation of the concepts. This representation is further developed with
      operating models and roles. Several information related scenarios covering both
      clinical and non-clinical domains are considered in information terms and then
      related back to the data governance framework. This assists the reader in
      understanding how data governance would help address the issues or achieve a
      better outcome. These elements together enable the reader to gain an
      understanding of the data governance framework and how it applies in practice.
      Finally, some practical advice is offered for establishing and operating data
      governance as well as approaches for justifying the investment. 

PMID- 24018526
TI  - Casemix systems and their applications.
AB  - Casemix systems are used in many countries around the world. The reasons for the
      popularity of casemix systems will be clear once their design features and
      applications are explained. The specific design issues for acute and other health
      care settings are discussed, along with their application to paying for care,
      utilisation review, quality assurance and clinical governance. The quality of the
      data is important to the integrity of these systems, and the chapter closes with
      a discussion of the causes of errors in the data and how the quality can be
      improved. 

PMID- 24018527
TI  - Issues of data governance associated with data mining in medical research:
      experiences from an empirical study.
AB  - This chapter is a review of data mining techniques used in medical research. It
      will cover the existing applications of these techniques in the identification of
      diseases, and also present the authors' research experiences in medical disease
      diagnosis and analysis. A computational diagnosis approach can have a significant
      impact on accurate diagnosis and result in time and cost effective solutions. The
      chapter will begin with an overview of computational intelligence concepts,
      followed by details on different classification algorithms. Use of association
      learning, a well recognised data mining procedure, will also be discussed. Many
      of the datasets considered in existing medical data mining research are
      imbalanced, and the chapter focuses on this issue as well. Lastly, the chapter
      outlines the need of data governance in this research domain. 

PMID- 24018528
TI  - Clinical decision support systems: data quality management and governance.
AB  - This chapter examines data quality management (DQM) and information governance
      (IG) of electronic decision support (EDS) systems so that they are safe and fit
      for use by clinicians and patients and their carers. This is consistent with the
      ISO definition of data quality as being fit for purpose. The scope of DQM & IG
      should range from data creation and collection in clinical settings, through
      cleaning and, where obtained from multiple sources, linkage, storage, use by the
      EDS logic engine and algorithms, knowledge base and guidance provided, to
      curation and presentation. It must also include protocols and mechanisms to
      monitor the safety of EDS, which will feedback into DQM & IG activities.
      Ultimately, DQM & IG must be integrated across the data cycle to ensure that the
      EDS systems provide guidance that leads to safe and effective clinical decisions
      and care. 

PMID- 24018531
TI  - Preface.

PMID- 24018532
TI  - Inactivation of tumor-specific CD8+ CTLs by tumor-infiltrating tolerogenic
      dendritic cells.
AB  - Cancer immunosurveillance failure is largely attributed to the insufficient
      activation of tumor-specific class I major histocompatibility complex (MHC)
      molecule (MHC-I)-restricted CD8+ cytotoxic T lymphocytes (CTLs). DEC-205+
      dendritic cells (DCs), having the ability to cross-present, can present captured
      tumor antigens on MHC-I alongside costimulatory molecules, inducing the priming
      and activation of tumor-specific CD8+ CTLs. It has been suggested that reduced
      levels of costimulatory molecules on DCs may be a cause of impaired CTL induction
      and that some tumors may induce the downregulation of costimulatory molecules on
      tolerogenic DCs. To examine such possibilities, we established two distinct types
      of murine hepatoma cell lines, named Hepa1-6-1 and Hepa1-6-2 (derived from Hepa1
      6 cells), and confirmed that they display similar antigenicities, as well as
      identical surface expression of MHC-I. We found that Hepa1-6-1 had the ability to
      grow continuously after subcutaneous implantation into syngeneic C57BL/6 mice and
      did not prime CD8+ CTLs. In contrast, Hepa1-6-2 cells, which display reduced
      levels of adhesion molecules, such as Intercellular Adhesion Molecule 1 (ICAM-1),
      failed to grow in vivo and efficiently primed CTLs. Moreover, Hepa1-6-1-derived
      factors, such as transforming growth factor (TGF)-beta1, vascular endothelial
      growth factor (VEGF) and alpha-fetoprotein (AFP), converted CD11c(high) MHC
      II(high) DEC-205+ DC subsets into tolerogenic cells, displaying downregulated
      costimulatory molecules and having impaired cross-presenting capacities. These
      immunosuppressive tolerogenic DCs appeared to inhibit the induction of tumor
      specific CD8+ CTLs and suppress their cytotoxic functions within the tumor.
      Together, the findings presented here provide a new method of cancer
      immunotherapy using the selective suppression, depletion or alteration of
      immunosuppressive tolerogenic DCs within tumors.

PMID- 24018533
TI  - Optimal conditions required for influenza A infection-enhanced cross-priming of
      CD8+ T cells specific to cell-associated antigens.
AB  - Dendritic cells can take up exogenous tumor antigens and present their antigenic
      epitopes to CD8+ T cells (T(CD8+)), a process called cross-presentation. Cross
      presentation is especially important in antitumor immunity because tumor cells,
      although carrying tumor antigens, do not activate naive T cells efficiently
      because of a lack of co-stimulatory molecules. Our group has recently shown that
      influenza A virus (IAV) infection of allogeneic cells lead to enhanced cross
      priming of T(CD8+) specific to cellular antigens. To develop this into a
      potential vaccine strategy, in this study, we have systematically investigated
      the numbers of allogeneic cells infected by IAV, IAV doses and their infectious
      activity, the length of in vitro infection and other associated factors. We have
      defined the optimal immune-enhancing conditions and we have also shown in vivo
      that such enhanced cross-priming did lead to enhanced tumor protection. The
      knowledge should be useful for developing more robust cancer vaccine.

PMID- 24018535
TI  - Dose-finding design using mixed-effect proportional odds model for longitudinal
      graded toxicity data in phase I oncology clinical trials.
AB  - Phase I oncology clinical trials are designed to identify the optimal dose that
      will be recommended for phase II trials. This dose is typically defined as the
      dose associated with a certain probability of severe toxicity during the first
      cycle of treatment, although toxicity is repeatedly measured over cycles on an
      ordinal scale. We propose a new adaptive dose-finding design using longitudinal
      measurements of ordinal toxic adverse events, with proportional odds mixed-effect
      models. Likelihood-based inference is implemented. The optimal dose is then the
      dose producing a target rate of severe toxicity per cycle. This model can also be
      used to identify cumulative or late toxicities. The performances of this approach
      were compared with those of the continual reassessment method in a simulation
      study. Operating characteristics were evaluated in terms of correct
      identification of the target dose, distribution of the doses allocated and power
      to detect trends in the risk of toxicities over time. This approach was also used
      to reanalyse data from a phase I oncology trial. Use of a proportional odds mixed
      effect model appears to be feasible in phase I dose-finding trials, increases the
      ability of selecting the correct dose and provides a tool to detect cumulative
      effects.

PMID- 24018536
TI  - Laplacian dynamics on general graphs.
AB  - In previous work, we have introduced a "linear framework" for time-scale
      separation in biochemical systems, which is based on a labelled, directed graph,
      G, and an associated linear differential equation, dx/dt = L(G) ? x, where L(G)
      is the Laplacian matrix of G. Biochemical nonlinearity is encoded in the graph
      labels. Many central results in molecular biology can be systematically derived
      within this framework, including those for enzyme kinetics, allosteric proteins,
      G-protein coupled receptors, ion channels, gene regulation at thermodynamic
      equilibrium, and protein post-translational modification. In the present paper,
      in response to new applications, which accommodate nonequilibrium mechanisms in
      eukaryotic gene regulation, we lay out the mathematical foundations of the
      framework. We show that, for any graph and any initial condition, the dynamics
      always reaches a steady state, which can be algorithmically calculated. If the
      graph is not strongly connected, which may occur in gene regulation, we show that
      the dynamics can exhibit flexible behavior that resembles multistability. We
      further reveal an unexpected equivalence between deterministic Laplacian dynamics
      and the master equations of continuous-time Markov processes, which allows
      rigorous treatment within the framework of stochastic, single-molecule
      mechanisms.

PMID- 24018538
TI  - The patient-centered medical home is not a pill: implications for evaluating
      primary care reforms.

PMID- 24018537
TI  - Differential ubiquitin-proteasome and autophagy signaling following rotator cuff
      tears and suprascapular nerve injury.
AB  - Previous studies have evaluated role of Akt/mTOR signaling in rotator cuff muscle
      atrophy and determined that there was differential in signaling following tendon
      transection (TT) and suprascapular nerve (SSN) denervation (DN), suggesting that
      atrophy following TT and DN was modulated by different protein degradation
      pathways. In this study, two muscle proteolytic systems that have been shown to
      be potent regulators of muscle atrophy in other injury models, the ubiquitin
      proteasome pathway and autophagy, were evaluated following TT and DN. In addition
      to examining protein degradation, this study assessed protein synthesis rate
      following these two surgical models to understand how the balance between protein
      degradation and synthesis results in atrophy following rotator cuff injury. In
      contrast to the traditional theory that protein synthesis is decreased during
      muscle atrophy, this study suggests that protein synthesis is up-regulated in
      rotator cuff muscle atrophy following both surgical models. While the ubiquitin
      proteasome pathway was a major contributor to the atrophy seen following DN,
      autophagy was a major contributor following TT. The findings of this study
      suggest that protein degradation is the primary factor contributing to atrophy
      following rotator cuff injury. However, different proteolytic pathways are
      activated if SSN injury is involved.

PMID- 24018539
TI  - Freeze-dried microalgae of Nannochloropsis oculata improve soybean oil's
      oxidative stability.
AB  - Marine microalga Nannochloropsis oculata possesses nutrients valuable for human
      health. In this study, we added freeze-dried N. oculata powder to soybean oil and
      observed a remarkable inhibition in oil oxidation. The amount of microalgae
      powder added was positively correlated to the increase in oil stability. The
      addition of 5.0 % (w/w) microalgae powder increased the oil stability index (OSI)
      values of soybean oil more than twofold at the tested temperatures 120 and 130 
      degrees C. N. oculata contains high levels of both phenolic compounds and alpha
      tocopherols that could be the contributors to such an increase of the OSI. Two
      methods were conducted to assay the active ingredients released from microalgae:
      one employed three solvent systems to extract the microalgae and the other was
      the soybean oil added with microalgae. Analyses of free radical scavenging and
      reducing power suggested that the phenolic compounds dominated the antioxidation
      activities in soybean oil when it was infused with the microalgae powder. Our
      results suggest that N. oculata could potentially be used as an additive in
      cooking oil to increase the shelf life and nutritional value of the oil and to
      reduce the production of free radicals from lipid oxidation when the oil is used
      at high-temperature cooking processes. 

PMID- 24018540
TI  - Extended-release intramuscular naltrexone (VIVITROL(r)): a review of its use in
      the prevention of relapse to opioid dependence in detoxified patients.
AB  - Naltrexone is a MU-opioid receptor antagonist that blocks the euphoric effects of
      heroin and prescription opioids. In order to improve treatment adherence, a once
      monthly, intramuscular, extended-release formulation of naltrexone (XR-NTX)
      [VIVITROL((r))] has been developed, and approved in the USA and Russia for the
      prevention of relapse to opioid dependence, after opioid detoxification. The
      clinical efficacy of this formulation in patients with opioid dependence was
      demonstrated in a 24-week, randomized, double-blind, placebo-controlled,
      multicentre, phase III trial (ALK21-013; n = 250). In this trial, opioid
      detoxified patients receiving XR-NTX 380 mg once every 4 weeks, in combination
      with psychosocial support, had a significantly higher median proportion of weeks
      of confirmed opioid abstinence during weeks 5-24, compared with those receiving
      placebo (primary endpoint). A significantly higher proportion of patients
      receiving XR-NTX achieved total confirmed abstinence during this period than
      those receiving placebo. XR-NTX was also associated with a significantly greater
      reduction in opioid craving and a significantly longer treatment retention period
      than placebo. XR-NTX was generally well tolerated in the phase III trial. The
      most common (incidence >=5 %) treatment-emergent adverse events that also
      occurred more frequently with XR-NTX than with placebo were hepatic enzyme
      abnormalities, nasopharyngitis, insomnia, hypertension, influenza and injection
      site pain. Thus, XR-NTX is a useful treatment option for the prevention of
      relapse to opioid dependence, following opioid detoxification. 

PMID- 24018541
TI  - Strategies for radiology reporting and communication : part 2: using visual
      imagery for enhanced and standardized communication.

PMID- 24018542
TI  - Design and implementation of a film dosimetry audit tool for comparison of
      planned and delivered dose distributions in high dose rate (HDR) brachytherapy.
AB  - A novel phantom is presented for 'full system' dosimetric audit comparing planned
      and delivered dose distributions in HDR gynaecological brachytherapy, using
      clinical treatment applicators. The brachytherapy applicator dosimetry test
      object consists of a near full-scatter water tank with applicator and film
      supports constructed of Solid Water, accommodating any typical cervix applicator.
      Film dosimeters are precisely held in four orthogonal planes bisecting the
      intrauterine tube, sampling dose distributions in the high risk clinical target
      volume, points A and B, bladder, rectum and sigmoid. The applicator position is
      fixed prior to CT scanning and through treatment planning and irradiation. The CT
      data is acquired with the applicator in a near clinical orientation to include
      applicator reconstruction in the system test. Gamma analysis is used to compare
      treatment planning system exported RTDose grid with measured multi-channel film
      dose maps. Results from two pilot audits are presented, using Ir-192 and Co-60
      HDR sources, with a mean gamma passing rate of 98.6% using criteria of 3% local
      normalization and 3 mm distance to agreement (DTA). The mean DTA between
      prescribed dose and measured film dose at point A was 1.2 mm. The phantom was
      funded by IPEM and will be used for a UK national brachytherapy dosimetry audit. 

PMID- 24018544
TI  - Self-induced multiple comas with recreational baclofen overdoses in an adolescent
      girl.

PMID- 24018543
TI  - GATA augments GNRH-mediated increases in Adcyap1 gene expression in pituitary
      gonadotrope cells.
AB  - Pituitary adenylate cyclase-activating polypeptide 1 (PACAP or ADCYAP1) regulates
      gonadotropin biosynthesis and secretion, both alone and in conjunction with GNRH.
      Initially identified as a hypothalamic-releasing factor, ADCYAP1 subsequently has
      been identified in pituitary gonadotropes, suggesting it may act as an autocrine
      paracrine factor in this tissue. GNRH has been shown to increase pituitary
      Adcyap1 gene expression through the interaction of CREB and jun/fos with CRE/AP1
      cis-elements in the proximal promoter. In these studies, we were interested in
      identifying additional transcription factors and cognate cis-elements which
      regulate Adcyap1 gene promoter activity and chose to focus on the GATA family of
      transcription factors known to be critical for both pituitary cell
      differentiation and gonadotropin subunit expression. By transient transfection
      and electrophoretic mobility shift assay analysis, we demonstrate that GATA2 and
      GATA4 stimulate Adcyap1 promoter activity via a GATA cis-element located at
      position -191 in the rat Adcyap1 gene promoter. Furthermore, we show that
      addition of GATA2 or GATA4 significantly augments GNRH-mediated stimulation of
      Adcyap1 gene promoter activity in the gonadotrope LbetaT2 cell line. Conversely,
      blunting GATA expression with specific siRNA inhibits the ability of GNRH to
      stimulate ADCYAP1 mRNA levels in these cells. These data demonstrate a complex
      interaction between GNRH and GATA on ADCYAP1 expression, providing important new
      insights into the regulation of gonadotrope function. 

PMID- 24018545
TI  - A randomized, double-blind comparison of atomoxetine and placebo on response
      inhibition and interference control in children and adolescents with autism
      spectrum disorder and comorbid attention-deficit/hyperactivity disorder symptoms.

PMID- 24018546
TI  - Lithium treatment in patients with Huntington disease and suicidal behavior.

PMID- 24018547
TI  - Brain-derived neurotrophic factor serum concentrations in acute depressive
      patients increase during lithium augmentation of antidepressants.
AB  - In recent years, lithium has proved an effective augmentation strategy of
      antidepressants in both acute and treatment-resistant depression. Neuroprotective
      and procognitive effects of lithium have been evidenced. Brain-derived
      neurotrophic factor (BDNF) has been shown to play a key role in the
      pathophysiology of several neurological and psychiatric disorders. The BDNF
      hypothesis of depression postulates that a loss of BDNF is directly involved in
      the pathophysiology of depression, and its restoration may underlie the
      therapeutic efficacy of antidepressant treatments. Brain-derived neurotrophic
      factor serum concentrations were measured in a total of 83 acutely depressed
      patients before and after 4 weeks of lithium augmentation. A significant BDNF
      increase has been found during treatment (F2,81 = 5.04, P < 0.05). Brain-derived
      neurotrophic factor concentrations at baseline correlated negatively with
      relative Hamilton Depression Scale change after treatment with lithium (n = 83; r
      = -0.23; P < 0.05). This is the first study showing that lithium augmentation of
      an antidepressant strategy can increase BDNF serum concentrations. Our study
      replicates previous findings showing that serum BDNF levels in patients with
      depressive episodes increase during effective antidepressant treatment. Further
      studies are needed to separate specific effects of different antidepressants on
      BDNF concentration and address potential BDNF downstream mechanisms. 

PMID- 24018548
TI  - Rheumatoid arthritis: stress affects rheumatoid arthritis, but via what
      mechanisms?

PMID- 24018549
TI  - Mechanical low back pain--a rheumatologist's view.
AB  - Low back pain, in its acute and chronic forms, is one of the most common health
      problems and is frequently evaluated by rheumatologists. The multiple possible
      diagnoses associated with this symptom make correctly attributing back pain to a
      specific disease difficult. This dilemma necessitates an organized approach to
      separate patients with mechanical disorders from those with rare systemic
      disorders. The most common forms of back pain are mechanical. Gradual
      modifications in the axial skeletal structures over time result in pathological
      disorders that generally occur later in an individual's lifespan. The diagnostic
      process that identifies these mechanical disorders is straightforward and does
      not require expensive radiological or laboratory tests in the early phases of the
      evaluation. Most low back pain resolves without intervention, but some reports
      suggest that episodes of back pain are persistent or recurring for a substantial
      minority of patients. Therapies for back pain can be nonpharmacological,
      pharmacological or surgical. All interventions have limited capacity to resolve
      low back pain. Nonsurgical therapies are preferred for muscle injuries and
      osteoarthritis of the lumbar spine. Surgical interventions can resolve the pain
      and dysfunction of disc herniation and spinal stenosis more rapidly than
      conventional therapy, but surgical benefit wanes over time. 

PMID- 24018551
TI  - A phosphorus-based compartmental ligand, (S)P[N(Me)N=CH-C6H3-2-O-3-OMe]3 (LH3),
      enables the assembly of luminescent heterobimetallic linear {L2Zn2Ln}+ [Ln = Gd,
      Tb, Nd and Eu] complexes.
AB  - The sequential reaction of a phosphorus-based trishydrazone ligand, LH3 with
      anhydrous ZnCl2 and LnCl3.6H2O in a 2 : 2 : 1 stoichiometric ratio in the
      presence of triethylamine as the base leads to the formation of monocationic
      trinuclear complexes [L2Zn2Ln]Cl {Ln = Gd (1), Tb (2), Nd (3), Eu (4) and L =
      [(S)P[N(Me)N=CH-C6H3-2-O-3-OMe]3}. All the three metal ions, in each of these
      compounds, are arranged in a linear fashion. The two terminal Zn(II) ions are
      encapsulated by three imino and three phenolate oxygen atoms while the lanthanide
      ion remains in the centre with an all-oxygen coordination environment. Detailed
      photophysical measurements reveal the complete absence of antenna sensitization
      in all the four complexes. However, a strong emission was found for 2 and 4 when
      excited directly at their f-f levels.

PMID- 24018552
TI  - Pneumococcal vaccination of older adults: conjugate or polysaccharide?

PMID- 24018554
TI  - Self-assembled clay films with a platelet-void multilayered nanostructure and
      flame-blocking properties.
AB  - Polymeric composite films with a high loading of nano-size silicates can hardly
      meet the increasingly stringent fireproof and smoke-free requirements during
      burning. Thus, it is desirable to prepare pure clay films that can block air,
      heat, and flame. Here we report an organic-free clay film capable of both flame-
      and heat-shielding. The film was prepared from the self-assembly of nanometer
      thick silicate platelets derived from the exfoliation of natural clays. The self
      assembled film has a highly regular multilayered nanostructure over a large area
      and an appreciable volume of air entrapped in between. The combination of regular
      structure and substantial air volume contributes to the low thermal conductivity
      and flame blocking property of the film. It was demonstrated that the film can
      shield flame over hour duration and prevent temperature rising on the backside of
      film. This remarkable clay film has a myriad of uses including gas barrier, heat
      insulator, and fireproof devices. 

PMID- 24018550
TI  - Future prospects in biologic therapy for systemic lupus erythematosus.
AB  - With the approval by the FDA in 2011 of a biologic agent (namely belimumab) for
      the treatment of systemic lupus erythematosus (SLE), optimism abounds that
      additional biologic (and nonbiologic) agents will be similarly endorsed. Given
      the numerous immune-based abnormalities associated with SLE, the potential
      therapeutic targets for biologic agents and the candidate biologic approaches are
      also numerous. These approaches include: biologic agents that promote B-cell
      depletion, B-cell inactivation, or the generation of regulatory B cells; biologic
      agents that induce T-cell tolerance, block T-cell activation and differentiation,
      or alter T-cell trafficking; biologic agents that target the B-cell activating
      factor (BAFF) axis, type I interferons, IL-6 and its receptor, or TNF; and the
      adoptive transfer of ex vivo-generated regulatory T cells. Owing to the great
      heterogeneity inherent to SLE, no single approach should be expected to be
      effective in all patients. As our understanding of the pathogenic mechanisms of
      SLE continues to expand, additional therapeutic targets and approaches will
      undoubtedly be identified and should be fully exploited. 

PMID- 24018555
TI  - Differential postural control and sensory organization in young tennis players
      and taekwondo practitioners.
AB  - This study compared the sensory organization and standing balance of adolescent
      tennis players, taekwondo (TKD) practitioners, and healthy control participants.
      Sixty participants including 12 tennis players, 21 TKD practitioners, and 27
      healthy control participants were tested. All of the participants underwent the
      Sensory Organization Test (SOT) and the Unilateral Stance Test (UST) on a Smart
      Equitest system. Results revealed that tennis players had higher SOT visual
      ratios than the control participants (p = .005), and TKD practitioners swayed
      more slowly in the UST than the control participants (p = .039). No differences
      (p > .05) were found in the composite score, somatosensory ratio, or vestibular
      ratio between the groups. Tennis players swayed less when they relied more on
      visual input to maintain balance, whereas TKD practitioners were more stable when
      standing on one leg. Parents may consider these sports as recreational activities
      for their children to develop specific balance abilities. 

PMID- 24018556
TI  - Emergency airway management: can we do better?

PMID- 24018557
TI  - FGF18 as a prognostic and therapeutic biomarker in ovarian cancer.
AB  - High-throughput genomic technologies have identified biomarkers and potential
      therapeutic targets for ovarian cancer. Comprehensive functional validation
      studies of the biological and clinical implications of these biomarkers are
      needed to advance them toward clinical use. Amplification of chromosomal region
      5q31-5q35.3 has been used to predict poor prognosis in patients with advanced
      stage, high-grade serous ovarian cancer. In this study, we further dissected this
      large amplicon and identified the overexpression of FGF18 as an independent
      predictive marker for poor clinical outcome in this patient population. Using
      cell culture and xenograft models, we show that FGF18 signaling promoted tumor
      progression by modulating the ovarian tumor aggressiveness and microenvironment.
      FGF18 controlled migration, invasion, and tumorigenicity of ovarian cancer cells
      through NF-kappaB activation, which increased the production of oncogenic
      cytokines and chemokines. This resulted in a tumor microenvironment characterized
      by enhanced angiogenesis and augmented tumor-associated macrophage infiltration
      and M2 polarization. Tumors from ovarian cancer patients had increased FGF18
      expression levels with microvessel density and M2 macrophage infiltration,
      confirming our in vitro results. These findings demonstrate that FGF18 is
      important for a subset of ovarian cancers and may serve as a therapeutic target. 

PMID- 24018558
TI  - Retinal angiogenesis suppression through small molecule activation of p53.
AB  - Neovascular age-related macular degeneration is a leading cause of irreversible
      vision loss in the Western world. Cytokine-targeted therapies (such as anti
      vascular endothelial growth factor) are effective in treating pathologic ocular
      angiogenesis, but have not led to a durable effect and often require indefinite
      treatment. Here, we show that Nutlin-3, a small molecule antagonist of the E3
      ubiquitin protein ligase MDM2, inhibited angiogenesis in several model systems.
      We found that a functional p53 pathway was essential for Nutlin-3-mediated
      retinal antiangiogenesis and disruption of the p53 transcriptional network
      abolished the antiangiogenic activity of Nutlin-3. Nutlin-3 did not inhibit
      established, mature blood vessels in the adult mouse retina, suggesting that only
      proliferating retinal vessels are sensitive to Nutlin-3. Furthermore, Nutlin-3
      inhibited angiogenesis in nonretinal models such as the hind limb ischemia model.
      Our work demonstrates that Nutlin-3 functions through an antiproliferative
      pathway with conceivable advantages over existing cytokine-targeted
      antiangiogenesis therapies. 

PMID- 24018559
TI  - Thrombospondin-1 mediates oncogenic Ras-induced senescence in premalignant lung
      tumors.
AB  - Progression of premalignant lesions is restrained by oncogene-induced senescence.
      Oncogenic Ras triggers senescence in many organs, including the lung, which
      exhibits high levels of the angiogenesis inhibitor thrombospondin-1 (TSP-1). The
      contribution of TSP-1 upregulation to the modulation of tumorigenesis in the lung
      is unclear. Using a mouse model of lung cancer, we have shown that TSP-1 plays a
      critical and cell-autonomous role in suppressing Kras-induced lung tumorigenesis
      independent of its antiangiogenic function. Overall survival was decreased in a
      Kras-driven mouse model of lung cancer on a Tsp-1-/- background. We found that
      oncogenic Kras-induced TSP-1 upregulation in a p53-dependent manner. TSP-1
      functioned in a positive feedback loop to stabilize p53 by interacting directly
      with activated ERK. TSP-1 tethering of ERK in the cytoplasm promoted a level of
      MAPK signaling that was sufficient to sustain p53 expression and a senescence
      response. Our data identify TSP-1 as a p53 target that contributes to maintaining
      Ras-induced senescence in the lung. 

PMID- 24018560
TI  - Perturbation of NK cell peripheral homeostasis accelerates prostate carcinoma
      metastasis.
AB  - The activating receptor NK cell group 2 member D (NKG2D) mediates antitumor
      immunity in experimental animal models. However, whether NKG2D ligands contribute
      to tumor suppression or progression clinically remains controversial. Here, we
      have described 2 novel lines of "humanized" bi-transgenic (bi-Tg) mice in which
      native human NKG2D ligand MHC class I polypeptide-related sequence B (MICB) or
      the engineered membrane-restricted MICB (MICB.A2) was expressed in the prostate
      of the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of
      spontaneous carcinogenesis. Bi-Tg TRAMP/MICB mice exhibited a markedly increased
      incidence of progressed carcinomas and metastasis, whereas TRAMP/MICB.A2 mice
      enjoyed long-term tumor-free survival conferred by sustained NKG2D-mediated
      antitumor immunity. Mechanistically, we found that cancer progression in
      TRAMP/MICB mice was associated with loss of the peripheral NK cell pool owing to
      high serum levels of tumor-derived soluble MICB (sMICB). Prostate cancer patients
      also displayed reduction of peripheral NK cells and high sMIC levels. Our study
      has not only provided direct evidence in "humanized" mouse models that soluble
      and membrane-restricted NKG2D ligands pose opposite impacts on cancer
      progression, but also uncovered a mechanism of sMIC-induced impairment of NK cell
      antitumor immunity. Our findings suggest that the impact of soluble NKG2D ligands
      should be considered in NK cell-based cancer immunotherapy and that our unique
      mouse models should be valuable for therapy optimization. 

PMID- 24018563
TI  - Intensive glucose control in hyperglycemic patients with acute coronary
      syndromes: still smoke, but no fire....

PMID- 24018561
TI  - Proximal tubule H-ferritin mediates iron trafficking in acute kidney injury.
AB  - Ferritin plays a central role in iron metabolism and is made of 24 subunits of 2
      types: heavy chain and light chain. The ferritin heavy chain (FtH) has
      ferroxidase activity that is required for iron incorporation and limiting
      toxicity. The purpose of this study was to investigate the role of FtH in acute
      kidney injury (AKI) and renal iron handling by using proximal tubule-specific FtH
      knockout mice (FtH(PT-/-) mice). FtH(PT-/-) mice had significant mortality, worse
      structural and functional renal injury, and increased levels of apoptosis in
      rhabdomyolysis and cisplatin-induced AKI, despite significantly higher expression
      of heme oxygenase-1, an antioxidant and cytoprotective enzyme. While expression
      of divalent metal transporter-1 was unaffected, expression of ferroportin (FPN)
      was significantly lower under both basal and rhabdomyolysis-induced AKI in FtH(PT
      /-) mice. Apical localization of FPN was disrupted after AKI to a diffuse
      cytosolic and basolateral pattern. FtH, regardless of iron content and
      ferroxidase activity, induced FPN. Interestingly, urinary levels of the iron
      acceptor proteins neutrophil gelatinase-associated lipocalin, hemopexin, and
      transferrin were increased in FtH(PT-/-) mice after AKI. These results underscore
      the protective role of FtH and reveal the critical role of proximal tubule FtH in
      iron trafficking in AKI.

PMID- 24018562
TI  - Lipotoxicity disrupts incretin-regulated human beta cell connectivity.
AB  - Pancreatic beta cell dysfunction is pathognomonic of type 2 diabetes mellitus
      (T2DM) and is driven by environmental and genetic factors. beta cell responses to
      glucose and to incretins such as glucagon-like peptide-1 (GLP-1) and glucose
      dependent insulinotropic polypeptide (GIP) are altered in the disease state.
      While rodent beta cells act as a coordinated syncytium to drive insulin release,
      this property is unexplored in human islets. In situ imaging approaches were
      therefore used to monitor in real time the islet dynamics underlying hormone
      release. We found that GLP-1 and GIP recruit a highly coordinated subnetwork of
      beta cells that are targeted by lipotoxicity to suppress insulin secretion. Donor
      BMI was negatively correlated with subpopulation responses to GLP-1, suggesting
      that this action of incretin contributes to functional beta cell mass in vivo.
      Conversely, exposure of mice to a high-fat diet unveiled a role for incretin in
      maintaining coordinated islet activity, supporting the existence of species
      specific strategies to maintain normoglycemia. These findings demonstrate that
      beta cell connectedness is an inherent property of human islets that is likely to
      influence incretin-potentiated insulin secretion and may be perturbed by
      diabetogenic insults to disrupt glucose homeostasis in humans. 

PMID- 24018564
TI  - Kidney cancer: Comparing first-line treatments for mRCC.

PMID- 24018565
TI  - Sexual dysfunction: Dapoxetine shown to be safe for premature ejaculation.

PMID- 24018566
TI  - Prostate cancer: mortality unaffected by finasteride treatment.

PMID- 24018568
TI  - Female urology: Growing evidence for robotic prolapse surgery.

PMID- 24018569
TI  - Forcing lateral electron disequilibrium to spare lung tissue: a novel technique
      for stereotactic body radiation therapy of lung cancer.
AB  - Stereotactic body radiation therapy (SBRT) has quickly become a preferred
      treatment option for early-stage lung cancer patients who are ineligible for
      surgery. This technique uses tightly conformed megavoltage (MV) x-ray beams to
      irradiate a tumour with ablative doses in only a few treatment fractions. Small
      high energy x-ray fields can cause lateral electron disequilibrium (LED) to occur
      within low density media, which can reduce tumour dose. These dose effects may be
      challenging to predict using analytic dose calculation algorithms, especially at
      higher beam energies. As a result, previous authors have suggested using low
      energy photons (<10 MV) and larger fields (>5 * 5 cm(2)) for lung cancer patients
      to avoid the negative dosimetric effects of LED. In this work, we propose a new
      form of SBRT, described as LED-optimized SBRT (LED-SBRT), which utilizes
      radiotherapy (RT) parameters designed to cause LED to advantage. It will be shown
      that LED-SBRT creates enhanced dose gradients at the tumour/lung interface, which
      can be used to manipulate tumour dose, and/or normal lung dose. To demonstrate
      the potential benefits of LED-SBRT, the DOSXYZnrc (National Research Council of
      Canada, Ottawa, ON) Monte Carlo (MC) software was used to calculate dose within a
      cylindrical phantom and a typical lung patient. 6 MV or 18 MV x-ray fields were
      focused onto a small tumour volume (diameter ~1 cm). For the phantom, square
      fields of 1 * 1 cm(2), 3 * 3 cm(2), or 5 * 5 cm(2) were applied. However, in the
      patient, 3 * 1 cm(2), 3 * 2 cm(2), 3 * 2.5 cm(2), or 3 * 3 cm(2) field sizes were
      used in simulations to assure target coverage in the superior-inferior direction.
      To mimic a 180 degrees  SBRT arc in the (symmetric) phantom, a single beam
      profile was calculated, rotated, and beams were summed at 1 degrees  segments to
      accumulate an arc dose distribution. For the patient, a 360 degrees  arc was
      modelled with 36 equally weighted (and spaced) fields focused on the tumour
      centre. A planning target volume (PTV) was generated by considering the extent of
      tumour motion over the patient's breathing cycle and set-up uncertainties. All
      patient dose results were normalized such that at least 95% of the PTV received
      at least 54 Gy (i.e. D95 = 54 Gy). Further, we introduce 'LED maps' as a novel
      clinical tool to compare the magnitude of LED resulting from the various SBRT arc
      plans. Results from the phantom simulation suggest that the best lung sparing
      occurred for RT parameters that cause severe LED. For equal tumour dose coverage,
      normal lung dose (2 cm outside the target region) was reduced from 92% to 23%,
      comparing results between the 18 MV (5 * 5 cm(2)) and 18 MV (1 * 1 cm(2)) arc
      simulations. In addition to reduced lung dose for the 18 MV (1 * 1 cm(2)) arc,
      maximal tumour dose increased beyond 125%. Thus, LED can create steep dose
      gradients to spare normal lung, while increasing tumour dose levels (if desired).
      In the patient simulation, a LED-optimized arc plan was designed using either 18
      MV (3 * 1 cm(2)) or 6 MV (3 * 3cm(2)) beams. Both plans met the D95 dose coverage
      requirement for the target. However, the LED-optimized plan increased the
      maximum, mean, and minimum dose within the PTV by as much as 80 Gy, 11 Gy, and 3
      Gy, respectively. Despite increased tumour dose levels, the 18 MV (3 * 1 cm(2))
      arc plan improved or maintained the V20, V5, and mean lung dose metrics compared
      to the 6 MV (3 * 3 cm(2)) simulation. We conclude that LED-SBRT has the potential
      to increase dose gradients, and dose levels within a small lung tumour. The
      magnitude of tumour dose increase or lung sparing can be optimized through
      manipulation of RT parameters (e.g. beam energy and field size). 

PMID- 24018567
TI  - Evolution of advanced technologies in prostate cancer radiotherapy.
AB  - Conventional treatment options for clinically localized, low-risk prostate cancer
      include radical prostatectomy, external-beam radiotherapy (EBRT) and low-dose
      rate brachytherapy. Advances in image-guided radiotherapy (IGRT) since the 1980s,
      the development of intensity-modulated radiotherapy (IMRT) during the 1990s and
      evidence from radiobiological models--which support the use of high doses per
      fraction--have developed alongside novel advanced radiotherapy modalities that
      include high-dose-rate brachytherapy (HDR-BT), stereotactic body radiotherapy
      (SBRT) and proton beam therapy. The relationship between the outcomes of and
      toxicities experienced by patients with prostate cancer treated with HDR-BT, SBRT
      and particle-beam therapy should provide urologists and oncologists an
      understanding of the continually evolving technology in prostate radiotherapy. On
      the basis of published evidence, conventionally fractionated EBRT with IMRT is
      considered the standard of care over conventional 3D conformal radiotherapy,
      whereas HDR-BT boost is an acceptable treatment option for selected patients with
      intermediate-risk and high-risk prostate cancer. SBRT and proton therapy should
      not be used for patients (regardless of disease risk group) outside the setting
      of a clinical trial. Finally, comparative effectiveness research should be
      conducted to provide a framework for evaluating advanced radiotherapy
      technologies by comparing the benefits and harms of available therapeutic options
      to optimize the risk:benefit ratio and improve cost effectiveness.

PMID- 24018570
TI  - Physiological and neurobiological bases of age-related hearing loss:
      biotherapeutic implications.
AB  - PURPOSE: The aim of this study was to highlight growing evidence of interactions
      between hormones and the structure and function of the auditory system. METHOD:
      Recent studies implicating sex hormones and other natural hormones in the
      modulation of hearing status in age-related hearing loss were reviewed. RESULTS:
      Progesterone, a sex hormone, has been shown to have negative effects on the
      hearing of older women and aging mice, whereas, in contrast, estrogen was found
      in some cases to have a positive influence. Aldosterone, used in studies of
      animal models of autoimmune hearing loss, slowed the progression of hearing loss.
      Follow-up studies in humans revealed that auditory measures varied as serum
      aldosterone levels shifted within the normal range, in otherwise healthy older
      subjects. This was true for simple as well as complex auditory tasks (i.e., sound
      spatial processing), suggesting benefits of aldosterone to postperipheral
      auditory processing as well. In addition, evidence suggests that this functional
      hearing improvement occurred in association with anatomical improvements to the
      stria vascularis--an important site of anatomical change in presbycusis.
      CONCLUSIONS: Audiology is now at the point where the search for biomedical
      interventions to modulate or prevent age-related hearing loss can move forward.
      Such interventions would require multidisciplinary collaborative initiatives by
      researchers in such areas as drug development, anatomy, auditory physiological
      and perceptual testing, and drug microdelivery systems.

PMID- 24018571
TI  - Hearing status in older persons: a significant determinant of depression and
      loneliness? Results from the longitudinal aging study amsterdam.
AB  - PURPOSE: In this study, the authors' aims were to (a) determine the longitudinal
      relationships between baseline hearing status and 4-year follow-up depression and
      loneliness in an older population and (b) investigate possible differences across
      subgroups in these relationships. METHOD: The authors used data from 2 waves of
      the Longitudinal Aging Study Amsterdam (4-year follow-up, baseline ages 63-93
      years). Sample sizes were 996 (self-report analyses) and 830 (speech-in-noise
      test analyses). The authors used multiple linear regression analyses to assess
      the associations between baseline hearing status and 4-year follow-up of
      depression, social loneliness, and emotional loneliness. Hearing was measured by
      self-report and by a speech-in-noise test. Age, gender, hearing aid use, baseline
      depression or loneliness, and relevant confounders and effect modifiers were
      incorporated. RESULTS: Both hearing measures showed significant associations with
      loneliness (p < .05), but these effects were confined to specific subgroups of
      older persons. For instance, adverse effects were confined to nonusers of hearing
      aids (self-report, social loneliness model) and men (self-report and speech-in
      noise test, emotional-loneliness model). No significant effects appeared for
      depression. CONCLUSION: Significant adverse effects of poor hearing on loneliness
      were found for specific subgroups of older persons. In future research,
      investigators should further examine the subgroup effects observed. Eventually,
      this may contribute to the development of tailored prevention programs.

PMID- 24018572
TI  - The effects of digital signal processing features on children's speech
      recognition and loudness perception.
AB  - PURPOSE: The purpose of this study was to determine the effects of hearing
      instruments set to Desired Sensation Level version 5 (DSL v5) hearing instrument
      prescription algorithm targets and equipped with directional microphones and
      digital noise reduction (DNR) on children's sentence recognition in noise
      performance and loudness perception in a classroom environment. METHOD: Ten
      children (ages 8-17 years) with stable, congenital sensorineural hearing losses
      participated in the study. Participants were fitted bilaterally with behind-the
      ear hearing instruments set to DSL v5 prescriptive targets. Sentence recognition
      in noise was evaluated using the Bamford-Kowal-Bench Speech in Noise Test
      (Niquette et al., 2003). Loudness perception was evaluated using a modified
      version of the Contour Test of Loudness Perception (Cox, Alexander, Taylor, &
      Gray, 1997). RESULTS: Children's sentence recognition in noise performance was
      significantly better when using directional microphones alone or in combination
      with DNR than when using omnidirectional microphones alone or in combination with
      DNR. Children's loudness ratings for sounds above 72 dB SPL were lowest when
      fitted with the DSL v5 Noise prescription combined with directional microphones.
      DNR use showed no effect on loudness ratings. CONCLUSION: Use of the DSL v5 Noise
      prescription with a directional microphone improved sentence recognition in noise
      performance and reduced loudness perception ratings for loud sounds relative to a
      typical clinical reference fitting with the DSL v5 Quiet prescription with no
      digital signal processing features enabled. Potential clinical strategies are
      discussed.

PMID- 24018574
TI  - Communication strategies and accommodations utilized by health care providers
      with hearing loss: a pilot study.
AB  - PURPOSE: Poor communication between health care providers and patients may
      negatively impact patient outcomes, and enhancing communication is one way to
      improve outcomes. Effective communication is particularly important for health
      care providers who have hearing loss. The authors found that a systematic survey
      of the communication strategies and experiences of health care providers with
      hearing loss had not yet been conducted. METHOD: In this pilot study, 32 health
      care professionals with hearing loss were recruited via the Association of
      Medical Professionals With Hearing Losses and were asked to complete a 28
      question survey. RESULTS: Health care providers with hearing loss already employ
      strategies that all health care providers are encouraged to use in order to
      enhance patient-provider communication, and survey participants have found the
      strategies to be effective. CONCLUSIONS: The communication techniques and
      assistive technologies used by individuals with hearing loss seem to be
      effective: All participants reported feeling able to communicate effectively with
      patients at least most of the time. More research is needed to determine if use
      of these communication techniques has similar results for health care providers
      without hearing loss.

PMID- 24018573
TI  - Timeliness of service delivery for children with later-identified mild-to-severe
      hearing loss.
AB  - PURPOSE: In this study, the authors examined diagnostic and intervention services
      for children identified with hearing loss (HL) after the newborn period. METHOD:
      The authors compared ages at service delivery and length of delays between
      service delivery steps for 57 later-identified children with HL and 193 children
      who referred for assessment from the newborn hearing screen (NHS). For only later
      identified children, regression models were used to investigate relationships
      among predictor variables and dependent variables related to service delivery.
      RESULTS: Children who referred from the NHS received follow-up services at
      younger ages than later-identified children. Later-identified children had
      significantly longer delays from HL confirmation to entry into early
      intervention, compared to children who referred from the NHS. For later
      identified children, degree of HL predicted ages at follow-up clinical services.
      Children with more severe HL received services at younger ages compared to
      children with milder HL. Gender predicted the length of the delay from
      confirmation to entry into early intervention, with girls demonstrating shorter
      delays. CONCLUSIONS: The current results lend support to the need for ongoing
      hearing monitoring programs after the neonatal period, particularly when children
      enter early intervention programs because of language/developmental delays.

PMID- 24018575
TI  - Learning to listen again: the role of compliance in auditory training for adults
      with hearing loss.
AB  - PURPOSE: To examine the role of compliance in the outcomes of computer-based
      auditory training with the Listening and Communication Enhancement (LACE) program
      in Veterans using hearing aids. METHOD: The authors examined available LACE
      training data for 5 tasks (i.e., speech-in-babble, time compression, competing
      speaker, auditory memory, missing word) from 50 hearing-aid users who
      participated in a larger, randomized controlled trial designed to examine the
      efficacy of LACE training. The goals were to determine: (a) whether there were
      changes in performance over 20 training sessions on trained tasks (i.e., on-task
      outcomes); and (b) whether compliance, defined as completing all 20 sessions, vs.
      noncompliance, defined as completing less than 20 sessions, influenced
      performance on parallel untrained tasks (i.e., off-task outcomes). RESULTS: The
      majority, 84% of participants, completed 20 sessions, with maximum outcome
      occurring with at least 10 sessions of training for some tasks and up to 20
      sessions of training for others. Comparison of baseline to posttest performance
      revealed statistically significant improvements for 4 of 7 off-task outcome
      measures for the compliant group, with at least small (0.2 < d < 0.3) Cohen's d
      effect sizes for 3 of the 4. There were no statistically significant improvements
      observed for the noncompliant group. CONCLUSION: The high level of compliance in
      the present study may be attributable to use of systematized verbal and written
      instructions with telephone follow-up. Compliance, as expected, appears important
      for optimizing the outcomes of auditory training. Methods to improve compliance
      in clinical populations need to be developed, and compliance data are important
      to report in future studies of auditory training.

PMID- 24018576
TI  - Improved gap detection thresholds following auditory training: evidence of
      auditory plasticity in older adults.
AB  - PURPOSE: IN this article, the authors aimed to measure the course of improvement
      in a gap-detection (GD) task following multisession training in older compared
      with young adults. METHOD: Participants with normal hearing (N= 30) were divided
      into 4 groups: 2 groups of older and young adults who received multisession
      training over 10 days (9 adults/group, Mage = 64.7 years and 24.1 years,
      respectively) and 2 control groups of older and young adults (6 adults/group,
      Mage = 65.4 years and 26.3 years, respectively). Stimuli consisted of silent gaps
      marked by 2 noise bands centered at 1000 Hz. GD thresholds (GDTs) were measured
      through use of an adaptive procedure in each testing day, 24 hr post-training and
      at 1 month post-training. RESULTS: Initial GDTs of the older group were
      significantly poorer than those of the young adults. However, by the fourth
      training day, the mean GDTs of the 2 groups were similar, and both groups showed
      the same rate of improvement in the following sessions. Data of the controls
      confirmed that the better GDTs of the trained groups resulted from their
      training. Retention of learning was demonstrated for both age groups.
      CONCLUSIONS: The data from this study support the notion that some aspects of
      auditory learning and temporal resolution may be preserved in the elderly.

PMID- 24018577
TI  - Examining speech perception in noise and cognitive functions in the elderly.
AB  - PURPOSE: The purpose of this study was to investigate the relationship of
      cognitive functions (i.e., working memory [WM]) and speech recognition against
      different background maskers in older individuals. METHOD: Speech reception
      thresholds (SRTs) were determined using a matrix-sentence test. Unmodulated
      noise, modulated noise (International Collegium for Rehabilitative Audiology
      [ICRA] noise 5-250), and speech fragments (International Speech Test Signal
      [ISTS]) were used as background maskers. Verbal WM was assessed using the Verbal
      Learning and Memory Test (VLMT; Helmstaedter & Durwen, 1990). Measurements were
      conducted with 14 normal-hearing older individuals and a control group of 12
      normal-hearing young listeners. RESULTS: Despite their normal hearing ability,
      the young listeners outperformed the older individuals in all background maskers.
      These differences were largest for the modulated maskers. SRTs were significantly
      correlated with the scores of the VLMT. A linear regression model also included
      WM as the only significant predictor variable. CONCLUSIONS: The results support
      the assumption that WM plays an important role for speech understanding and that
      it might have impact on results obtained using speech audiometry. Thus, an
      individual's WM capacity should be considered with aural diagnosis and
      rehabilitation. The VLMT proved to be a clinically applicable test for WM.
      Further cognitive functions important with speech understanding are currently
      being investigated within the SAKoLA (Sprachaudiometrie und kognitive Leistungen
      im Alter [Speech Audiometry and Cognitive Functions in the Elderly]) project.

PMID- 24018578
TI  - Transitioning from bimodal to bilateral cochlear implant listening: speech
      recognition and localization in four individuals.
AB  - PURPOSE: The use of bilateral stimulation is becoming common for cochlear implant
      (CI) recipients with either (a) a CI in one ear and a hearing aid (HA) in the
      nonimplanted ear (CI&HA-bimodal) or (b) CIs in both ears (CI&CI-bilateral). The
      objective of this study was to evaluate 4 individuals who transitioned from
      bimodal to bilateral stimulation. METHOD: Participants had completed a larger
      study of bimodal hearing and subsequently received a second CI. Test procedures
      from the bimodal study, including roaming speech recognition, localization, and a
      questionnaire (the Speech, Spatial, and Qualities of Hearing Scale; Gatehouse &
      Noble, 2004) were repeated after 6-7 months of bilateral CI experience. RESULTS:
      Speech recognition and localization were not significantly different between
      bimodal and unilateral CI. In contrast, performance was significantly better with
      CI&CI compared with unilateral CI. Speech recognition with CI&CI was
      significantly better than with CI&HA for 2 of 4 participants. Localization was
      significantly better for all participants with CI&CI compared with CI&HA. CI&CI
      performance was rated as significantly better on the Speech, Spatial, and
      Qualities of Hearing Scale compared with CI&HA. CONCLUSIONS: There was a strong
      preference for CI&CI for all participants. The variability in speech recognition
      and localization, however, suggests that performance under these stimulus
      conditions is individualized. Differences in hearing and/or HA history may
      explain performance differences.

PMID- 24018579
TI  - Establishing a central zone in scaphoid surgery: a computational approach.
AB  - PURPOSE: Scaphoid fractures are commonly fixed with headless cannulated screws
      positioned centrally in the scaphoid. Judgement of central placement of the screw
      may be difficult. We generated a central zone using computer analysis of 3D
      reconstructions of computed tomography (CT) images. As long as the screw axis is
      completely contained within this central zone, the screw would be considered as
      centrally placed. METHODS: Thirty cases of 3D CT reconstructions of normal
      scaphoids in a computerised operation planning and simulation system (Vxwork
      software) were obtained. The central zone was established after some distance
      shrinkage of the original scaphoid surface reconstruction model using the
      function "erode" in the software. The shape of the central zone was evaluated,
      and the width of the central zone in the proximal pole, waist portion and distal
      pole was measured. We also established the long axis of the scaphoid to see
      whether it stays in the central zone. RESULTS: All central zones could be divided
      into distal, waist and proximal portions according to the corresponding irregular
      shape of the scaphoid. As the geometry of the central zone was so irregular and
      its width very narrow, it was possible to completely contain the screw axis
      either in the proximal portion alone, waist alone or distal central zone alone.
      CONCLUSIONS: Establishing the central zone of scaphoid 3D CT images provided a
      baseline for discussion of central placement of a scaphoid screw. The geometry of
      the scaphoid central zone determined that the screw could hardly be inserted
      through entire scaphoid central area during surgery.

PMID- 24018582
TI  - Use of acid-suppressive drugs in pregnancy and the risk of childhood asthma:
      bidirectional crossover study using the general practice research database.
AB  - BACKGROUND: Recent studies have reported an association between maternal use of
      gastric acid-suppressive drugs during pregnancy and asthma in the offspring, but
      the association could have been confounded by unmeasured risk factors. OBJECTIVE:
      We assessed the association between the use of acid-suppressive drugs during
      pregnancy and the risk of developing childhood asthma using a bidirectional
      crossover design. METHODS: Mother-infant matched sets in the UK General
      Practitioners Research Database were used to identify children with a drug
      treated asthma diagnosis during the years 2006-2010 who were matched to a sibling
      without asthma as controls. Primary exposure was use of any anti-suppressive drug
      during pregnancy, and subgroup analyses were conducted according to drug class
      (e.g. proton pump inhibitors or histamine 2 receptor antagonists) and trimester.
      Conditional logistic regression was used to estimate odds ratios (OR) with their
      corresponding 95 % confidence intervals (CIs). RESULTS: A total of 1,874 children
      with asthma and 1,874 control siblings were included in the analysis. The
      exposure rate among case and control pregnancies was 22 and 20 %, respectively.
      After adjustments for gender, birth order, mother's age and general practice
      visits, the exposure to any gastric-acid suppressive drug during pregnancy
      slightly increased the risk for developing asthma (OR 1.23, 95 % CI 1.01-1.51; p
      = 0.042). A trend towards increased risks was observed for those who used proton
      pump inhibitors and/or histamine 2 receptor antagonists (adjusted OR 1.72, 95 %
      CI 1.00-2.98; p = 0.048). CONCLUSIONS: These findings lend support to the
      emerging evidence that exposure to acid-suppressive drugs during pregnancy is
      associated with childhood asthma. More basic research is now warranted to
      investigate the mechanisms.

PMID- 24018583
TI  - Amino acid side chain induced selectivity in the hydrolysis of peptides catalyzed
      by a Zr(IV)-substituted Wells-Dawson type polyoxometalate.
AB  - In this paper the reactivity of K15H[Zr(alpha2-P2W17O61)2].25H2O (1), a Zr(IV)
      substituted Wells-Dawson polyoxometalate, is examined towards a series of Gly-Aa,
      Aa-Gly or Aa-Ser dipeptides, in which the nature and the size of the Aa amino
      acid side chain were varied. The rate of peptide bond hydrolysis, determined by
      (1)H NMR experiments, in Gly-Aa dipeptides is strongly dependent on the molecular
      volume and the chemical structure of the Aa side chain. When the volume of the
      aliphatic side chain of the Aa residue in Gly-Aa increased, a clear decrease in
      the hydrolysis rate was observed. Replacing one alpha-H in the C-terminal Gly
      residue of Gly-Gly by a methyl group (Gly-Ala) resulted in a 6-fold reactivity
      decrease, pointing towards the importance of steric factors for efficient peptide
      bond hydrolysis. The rate constants for peptide bond hydrolysis in Gly-Aa
      dipeptides at pD 5.0 and 60  degrees C ranged from 208.0 +/- 15.6 * 10(-6) min(
      1) for Gly-Ser to 5.0 +/- 1.0 * 10(-6) min(-1) for Gly-Glu, reflecting the
      influence of the different nature of the amino acid side chains on the hydrolysis
      rate. Faster hydrolysis was observed for peptides containing Ser and Thr since
      the hydroxyl group in their side chain is able to facilitate amide bond
      hydrolysis by promoting an N->O acyl rearrangement. Peptides containing
      positively charged side chains at pD 5.0 show enhanced hydrolysis rates as a
      result of the secondary electrostatic interactions with the negatively charged
      surface of the polyoxometalate, which stabilize the peptide-polyoxometalate
      complex. A slow hydrolysis rate was observed for Gly-Glu, because of the
      preferential coordination of the carboxylate group in the side chain of Glu to
      Zr(IV), which prevents coordination of the peptide carbonyl group and its
      activation towards hydrolysis.

PMID- 24018585
TI  - Development and validation of the Good Outcome Following Attempted Resuscitation
      (GO-FAR) score to predict neurologically intact survival after in-hospital
      cardiopulmonary resuscitation.
AB  - IMPORTANCE: Informing patients and providers of the likelihood of survival after
      in-hospital cardiac arrest (IHCA), neurologically intact or with minimal
      deficits, may be useful when discussing do-not-attempt-resuscitation orders.
      OBJECTIVE: To develop a simple prearrest point score that can identify patients
      unlikely to survive IHCA, neurologically intact or with minimal deficits. DESIGN,
      SETTING, AND PARTICIPANTS: The study included 51,240 inpatients experiencing an
      index episode of IHCA between January 1, 2007, and December 31, 2009, in 366
      hospitals participating in the Get With the Guidelines-Resuscitation registry.
      Dividing data into training (44.4%), test (22.2%), and validation (33.4%) data
      sets, we used multivariate methods to select the best independent predictors of
      good neurologic outcome, created a series of candidate decision models, and used
      the test data set to select the model that best classified patients as having a
      very low (<1%), low (1%-3%), average (>3%-15%), or higher than average (>15%)
      likelihood of survival after in-hospital cardiopulmonary resuscitation for IHCA
      with good neurologic status. The final model was evaluated using the validation
      data set. MAIN OUTCOMES AND MEASURES: Survival to discharge after in-hospital
      cardiopulmonary resuscitation for IHCA with good neurologic status
      (neurologically intact or with minimal deficits) based on a Cerebral Performance
      Category score of 1. RESULTS: The best performing model was a simple point score
      based on 13 prearrest variables. The C statistic was 0.78 when applied to the
      validation set. It identified the likelihood of a good outcome as very low in
      9.4% of patients (good outcome in 0.9%), low in 18.9% (good outcome in 1.7%),
      average in 54.0% (good outcome in 9.4%), and above average in 17.7% (good outcome
      in 27.5%). Overall, the score can identify more than one-quarter of patients as
      having a low or very low likelihood of survival to discharge, neurologically
      intact or with minimal deficits after IHCA (good outcome in 1.4%). CONCLUSIONS
      AND RELEVANCE: The Good Outcome Following Attempted Resuscitation (GO-FAR)
      scoring system identifies patients who are unlikely to benefit from a
      resuscitation attempt should they experience IHCA. This information can be used
      as part of a shared decision regarding do-not-attempt-resuscitation orders.

PMID- 24018586
TI  - Comparison of the effect of intra-tendon applications of recombinant human
      platelet-derived growth factor-BB, platelet-rich plasma, steroids in a rat
      achilles tendon collagenase model.
AB  - This study compared the effect of intra-tendon (IT) delivery of recombinant human
      platelet-derived growth factor-BB (rhPDGF-BB), platelet-rich plasma (PRP) and
      corticosteroids in a rat tendinopathy model. Seven days after collagenase
      induction of tendinopathy, a 30-ul IT injection was administered. Treatments
      included: saline; 3 ug rhPDGF-BB; 10 ug rhPDGF-BB; PRP; and 300 ug triamcinolone
      acetonide (TCA). Outcomes were assessed 7 and 21 days after treatment. All groups
      exhibited good to excellent repair. Relative to saline, cell proliferation
      increased 65% in the 10 ug rhPDGF-BB group and decreased 74% in the TCA group;
      inflammation decreased 65% in the TCA group. At 7 days, maximum load-to-failure
      was increased in the 3 ug rhPDGF-BB group relative to saline, PRP, and TCA (p <
      0.025). On day 21, maximum load-to-rupture was increased in the 10 ug rhPDGF-BB
      group relative to saline, PRP, and TCA (p < 0.035) and in the 3 ug rhPDGF-BB
      group compared to saline and TCA (p < 0.027). Stiffness in the 10 ug rhPDGF-BB
      group was increased compared to saline, PRP, and TCA (p < 0.038). Histology
      demonstrated similar repair in all groups. PRP and TCA did not improve mechanical
      properties compared to saline. Injections of rhPDGF-BB increased maximum load-to
      failure (3 and 10 ug) and stiffness (10 ug) relative to controls and commonly
      used treatments. (c) 2013 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res 32:145-150, 2014.

PMID- 24018587
TI  - Botulinum toxin for masseter hypertrophy.
AB  - BACKGROUND: Benign masseter muscle hypertrophy is an uncommon clinical phenomenon
      of uncertain aetiology which is characterised by a soft swelling near the angle
      of the mandible. The swelling may on occasion be associated with facial pain and
      can be prominent enough to be considered cosmetically disfiguring. Varying
      degrees of success have been reported for some of the treatment options for
      masseter hypertrophy, which range from simple pharmacotherapy to more invasive
      surgical reduction. Injection of botulinum toxin type A into the masseter muscle
      is generally considered a less invasive modality and has been advocated for
      cosmetic sculpting of the lower face. Botulinum toxin type A is a powerful
      neurotoxin which is produced by the anaerobic organism Clostridium botulinum and
      when injected into a muscle causes interference with the neurotransmitter
      mechanism producing selective paralysis and subsequent atrophy of the muscle.This
      review is an update of a previously published Cochrane review. OBJECTIVES: To
      assess the efficacy and safety of botulinum toxin type A compared to placebo or
      no treatment, for the management of benign bilateral masseter hypertrophy. SEARCH
      METHODS: We searched the following databases from inception to April 2013: the
      Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (via PubMed);
      EMBASE (via embase.com); Web of Science; CINAHL; Academic Search Premier (via
      EBSCOhost); ScienceDirect; LILACS (via BIREME); PubMed Central and Google Scholar
      (from 1700 to 19 April 2013). We searched two bibliographic databases of regional
      journals (IndMED and Iranmedex) which were expected to contain relevant trials.
      We also searched reference lists of relevant articles and contacted investigators
      to identify additional published and unpublished studies. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) and controlled clinical trials (CCTs)
      comparing intra-masseteric injections of botulinum toxin versus placebo
      administered for cosmetic facial sculpting in individuals of any age with
      bilateral benign masseter hypertrophy, which had been self-evaluated and
      confirmed by clinical and radiological examination were considered for inclusion.
      We excluded participants with unilateral or compensatory contralateral masseter
      hypertrophy resulting from head and neck radiotherapy. DATA COLLECTION AND
      ANALYSIS: Two review authors independently screened the search results. For
      future updates, two authors will independently extract data and assess trial
      quality using the Cochrane risk of bias tool. Risk ratios (RR) and corresponding
      95% confidence intervals (CI) will be calculated for all dichotomous outcomes and
      the mean difference (MD) and 95% CI will be calculated for continuous outcomes.
      MAIN RESULTS: We retrieved 683 unique references to studies. After screening
      these references 660 were excluded for being non-applicable. We assessed 23 full
      text articles for eligibility and all of these studies were excluded from the
      review. AUTHORS' CONCLUSIONS: We were unable to identify any RCTs or CCTs
      assessing the efficacy and safety of intra-masseteric injections of botulinum
      toxin for people with bilateral benign masseter hypertrophy. The absence of high
      level evidence for the effectiveness of this intervention emphasises the need for
      well-designed, adequately powered RCTs.

PMID- 24018589
TI  - Bouveret's syndrome complicated by classic gallstone ileus: progression of
      disease or iatrogenic?
AB  - CASE PRESENTATION: Bouveret's syndrome is a rare variant of gallstone ileus
      resulting in gastroduodenal obstruction from an impacted gallstone. We report two
      cases of Bouveret's syndrome that were complicated by classic (distal) gallstone
      ileus, which has previously been reported only twice. The first patient presented
      with vomiting, epigastric pain, and what was initially believed to be a duodenal
      diverticulum on computed tomography scan and endoscopy. He initially improved,
      but later developed symptoms of a small bowel obstruction. Repeat imaging
      revealed a classic distal gallstone ileus. The second patient presented with
      nausea, abdominal pain, and imaging consistent with Bouveret's syndrome. Multiple
      non-operative endoscopic techniques and extracorporeal shock wave lithotripsy
      were employed to fragment and retrieve the obstructing stone, and she
      subsequently developed a distal gallstone ileus from a stone fragment. Both
      patients were managed operatively with enterotomy and stone removal. DISCUSSION:
      These cases highlight a rare complication of Bouveret's syndrome, classic
      (distal) gallstone ileus, and juxtapose the natural history of a stone passing
      versus an iatrogenic etiology. We review the presentation and management of
      Bouveret's syndrome though no clear consensus exists as to the optimal treatment
      of these patients. We recommend that therapy should be decided on a case-by-case
      basis.

PMID- 24018590
TI  - Trends in the multimodality treatment of resectable colorectal liver metastases:
      an underutilized strategy.
AB  - OBJECTIVE: Advances in multimodality therapy have led to increased survival for
      patients with metastatic colorectal cancer, but the impact on patients undergoing
      resection for colorectal liver metastases is unclear. The purpose of this study
      was to evaluate patterns of treatment for resectable colorectal liver metastases
      in the USA over the last two decades. METHODS: Using the Surveillance,
      Epidemiology, and End Results-Medicare database, 1,926 patients who underwent
      hepatic resection for colorectal liver metastasis between 1991 and 2007 were
      included and divided into two cohorts: period 1 (1991-2000) and period 2 (2001
      2007). Demographic data, treatment patterns, and outcomes of the two periods were
      compared by univariate methods. Multivariable regression models were constructed
      to predict the use of perioperative chemotherapy, postoperative complications,
      and 90-day mortality following liver resection. RESULTS: The overall use of
      perioperative chemotherapy was 33 % and did not differ between periods, but
      shifted from postoperative to preoperative over time. By multivariable analysis,
      older age, black race, stage III primary cancer, and metachronous disease were
      predictive of lesser likelihood of chemotherapy use. The use of preoperative
      chemotherapy was not associated with any increase in perioperative morbidity or
      mortality. CONCLUSIONS: Despite increased survival and widespread recommendations
      for the use of multimodality therapy, the overall resection rate and use of
      perioperative chemotherapy for resectable colorectal liver metastases remain
      underutilized and have not increased over time. Efforts to investigate barriers
      to the widespread use of multimodality therapy for these patients are warranted.

PMID- 24018591
TI  - Laparoscopic Heller myotomy can be used as primary therapy for esophageal
      achalasia regardless of age.
AB  - INTRODUCTION: Laparoscopic Heller-Dor surgery is the current treatment of choice
      for patients with esophageal achalasia, but elderly patients are generally
      referred for less invasive treatments (pneumatic dilations or botulinum toxin
      injections). AIM: To assess the effect of age on the surgical outcome of patients
      receiving laparoscopic Heller-Dor as primary treatment. METHODS: Demographic and
      clinical findings were prospectively collected on patients undergoing
      laparoscopic Heller-Dor from 1992 to 2012. Patients were classified in three age
      brackets: group A (<=45 years), group B (45-70), and group C (>=70). Treatment
      was defined as a failure if the postoperative symptom score was >10th percentile
      of the preoperative score (i.e., >8). We consecutively performed the Heller-Dor
      in 571 achalasia patients, 305 (53.4 %) in group A, 226 (39.6 %) in group B, and
      40 (7 %) in group C. RESULTS: The mortality was nil; the conversion and morbidity
      rates were both 1.1 %. Group C patients had higher preoperative symptom scores (p
      = 0.02), while the symptom duration was similar in all three groups. Mucosal
      tears occurred in 17 patients (3 %): 6 (2 %) in group A, 8 (3.5 %) in group B,
      and 3 (7.5 %) in group C (p = 0.09). The postoperative hospital stay was slightly
      longer for group C (p = 0.06). DISCUSSION: The treatment failure rate was quite
      similar: 31 failures in group A (10.1 %), 19 in group B (8.4 %), and 3 in group C
      (7.5 %; p = 0.80). These failures were seen more in manometric pattern III (22.2
      %, p = 0.002). Laparoscopic Heller-Dor can be used as the first therapeutic
      approach to achalasia even in elderly patients with an acceptable surgical risk.

PMID- 24018592
TI  - Individual patient data meta-analysis of organ failure in acute pancreatitis:
      protocol of the PANCREA II study.
AB  - CONTEXT: Organ failure is a major determinant of mortality in patients with acute
      pancreatitis. These patients usually require admission to high dependency or
      intensive care units and consume considerable health care resources. Given a low
      incidence rate of organ failure and a lack of large non-interventional studies in
      the field of acute pancreatitis, the characteristics of organ failure that
      influence outcomes of patients with acute pancreatitis remain largely unknown.
      Therefore, the Pancreatitis Across Nations Clinical Research and Education
      Alliance (PANCREA) aims to conduct a meta-analysis of individual patient data
      from prospective non-interventional studies to determine the influence of timing,
      duration, sequence, and combination of different organ failures on mortality in
      patients with acute pancreatitis. METHODS: Pancreatologists currently active with
      acute pancreatitis clinical research will be invited to contribute. To be
      eligible for inclusion patients will have to meet the criteria of acute
      pancreatitis, develop at least one organ failure during the first week of
      hospitalization, and not be enrolled into an intervention study. Raw data will
      then be collated and checked. Individual patient data analysis based on a
      logistic regression model with adjustment for confounding variables will be done.
      For all analyses, corresponding 95% confidence intervals and P values will be
      reported. CONCLUSION: This collaborative individual patient data meta-analysis
      will answer important clinical questions regarding patients with acute
      pancreatitis that develop organ failure. Information derived from this study will
      be used to optimize routine clinical management and improve care strategies. It
      can also help validate outcome definitions, allow comparability of results and
      form a more accurate basis for patient allocation in further clinical studies.

PMID- 24018594
TI  - A retrospective study of capecitabine/temozolomide (CAPTEM) regimen in the
      treatment of metastatic pancreatic neuroendocrine tumors (pNETs) after failing
      previous therapy.
AB  - CONTEXT: Pancreatic neuroendocrine tumors (pNETs) are notoriously resistant to
      currently available chemotherapy agents. Preclinical data has suggested synergy
      between temozolomide and capecitabine. OBJECTIVE: To report a retrospective data
      on the efficacy and safety of capecitabine and temozolomide (CAPTEM regimen) in
      patients with metastatic pancreatic neuroendocrine tumors (pNETs) who have failed
      prior therapies. METHODS: We reviewed the medical records of 7 patients with
      metastatic pNETs who had had progressive cancer prior to treatment despite
      therapy, including long-acting release octreotide (60 mg/month), chemotherapy and
      hepatic chemoembolization. Capecitabine was administered at a flat dose of 1,000
      mg orally twice daily on days 1-14 and temozolomide 200 mg/m2 was given in two
      divided doses daily on days 10-14 of a 28-day cycle. Tumor assessments were
      repeated every two cycles and serum tumor markers were measured every cycle.
      Response to treatment was assessed using Response Evaluation Criteria in Solid
      Tumors (RECIST) parameters, and toxicity was graded using the National Cancer
      Institute Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.
      RESULTS: Among 7 patients treated, three patients achieved a partial response,
      and two patients had stable disease. Total response rate was 43%, and clinical
      benefit (responders and stable disease) was 71%. Median duration of response was
      8 months (range: 4-12 months). Grade 3 and 4 toxicities included grade 3
      thrombocytopenia in one patient and grade 3 fatigue in one patient. The most
      common toxicities were grade 1 and 2 neutropenia, grade 1 fatigue, grade 1 and 2
      hand-foot syndrome. CONCLUSIONS: Our retrospective study showed that modified
      CAPTEM regimen was well-tolerated and produced comparable response to historical
      data in neuroendocrine tumors, including pNETs. Our study is unique as it only
      included patients with pNETs. Further prospective studies are warranted to
      evaluate the combination of CAPTEM regimen with targeted therapies in pNETs.

PMID- 24018593
TI  - Performance characteristics of endoscopic ultrasound in the staging of pancreatic
      cancer: a meta-analysis.
AB  - CONTEXT: The optimal approach to pre-operative imaging assessment of pancreatic
      cancer is unknown. OBJECTIVE: The aim of this meta-analysis was to assess
      accuracy and performance characteristics of EUS in determining nodal staging,
      vascular invasion, and prediction of resectability of pancreatic cancer. A
      secondary aim was to perform head to head comparison of performance
      characteristics between EUS and CT for nodal staging, vascular invasion and
      resectability. DESIGN: Data from EUS studies were pooled according to bivariate
      generalized random effects model. Pooled estimates for CT were obtained from
      studies which performed head to head comparison between EUS and CT. PATIENTS:
      Patients with pancreatic cancer undergoing pre-operative imaging assessment.
      INTERVENTION: EUS. MAIN OUTCOME MEASURE: Pooled sensitivity, specificity,
      positive and negative predictive values of EUS for nodal staging, vascular
      invasion and resectability. RESULTS: Forty-nine studies were considered of which
      29 met inclusion criteria with a total of 1,330 patients. Pooled summary
      estimates for EUS-nodal staging were 69% for sensitivity and 81% for specificity.
      For vascular invasion, sensitivity was 85% and specificity was 91%. The
      sensitivity and specificity for resectability was 90% and 86%, respectively. CT
      scan showed lower sensitivity than EUS for nodal staging (24% vs. 58%) and
      vascular invasion (58% vs. 86%); however, the specificities for nodal staging
      (88% vs. 85%) and vascular invasion (95% vs. 93%) were comparable in studies
      where both imaging techniques were performed. The sensitivity and specificity of
      CT in determining resectability (90% and 69%) was similar to that of EUS (87% and
      89%). CONCLUSIONS: EUS is an accurate pre-operative tool in the assessment of
      nodal staging, vascular invasion and resectability in patients with pancreatic
      cancer.

PMID- 24018596
TI  - Renal lesions in autoimmune pancreatitis: diffusion weighted magnetic resonance
      imaging for assessing response to corticosteroid therapy.
AB  - CONTEXT: Autoimmune pancreatitis is a rare disorder characterized by the systemic
      deposition of IgG4 plasma cells. Extrapancreatic manifestations of autoimmune
      pancreatitis depend on the site of plasma cell deposition. The most common
      extrapancreatic site of involvement is the bile duct followed by the
      retroperitoneum and kidneys. CASE REPORT: We report a case of a patient with
      autoimmune pancreatitis and renal lesions who underwent MRI prior to and after
      corticosteroid therapy. CONCLUSION: We emphasize the role of diffusion weighted
      imaging (DWI) and apparent diffusion coefficient (ADC) findings on MRI in
      evaluating the response to steroid therapy.

PMID- 24018595
TI  - Autoimmune pancreatitis complicated by spontaneous subcapsular splenic
      haemorrhage.
AB  - CONTEXT: Autoimmune pancreatitis is a rare but increasingly recognised condition
      with unique clinical, immunological and histological features. We report the
      first case of autoimmune pancreatitis associated with spontaneous splenic
      haemorrhage. CASE REPORT: A 75-year-old man presented with severe epigastric pain
      radiating to the back associated with nausea and vomiting. A CT-scan of his
      abdomen showed a large pseudocyst within the pancreatic tail as well as a
      subcapsular splenic haemorrhage. His IgG4 levels were elevated and clinical
      history and investigations were consistent with severe acute pancreatitis, but
      were negative for other known causes of pancreatic disease. The patient was
      started on steroid therapy and improved dramatically clinically, immunologically
      and radiologically thus confirming the diagnosis of autoimmune pancreatitis. His
      splenic haemorrhage was managed conservatively in view of his haemodynamic
      stablity and eventually self-resolved. CONCLUSION: Autoimmune pancreatitis should
      not be overlooked in cases of acute pancreatitis without other obvious etiology.
      Furthermore, superimposed splenic haemorrhage is a rare but important
      complication of autoimmune pancreatitis.

PMID- 24018597
TI  - Pancreatic glucagonoma metastasising to the right ovary five years after initial
      surgery: a case report.
AB  - CONTEXT: Glucagonomas of the pancreas are neuroendocrine tumours (NETs) that
      arise from well-differentiated neuroendocrine cells within the pancreatic islets.
      They are considered to be aggressive NETs and often have metastases at initial
      presentation. In contrast localised glucagonoma without metastatic spread may
      have prolonged disease free survival with radical resectional surgery. CASE
      REPORT: The authors present a case of a glucagonoma that initially presented with
      classical necrolytic migratory erythema and a large solitary mass in the body and
      tail of the pancreas that was surgically resected. Five years after surgery the
      patient presented with increased serum glucagon levels and a mass in the right
      ovary. Pathology of the resected ovary after oophorectomy identified this as an
      isolated metastatic glucagonoma. CONCLUSION: Glucagonoma is a rare pancreatic NET
      that has significant malignant potential. This is the first case of a pancreatic
      glucagonoma metastasising to the ovary 5 years after radical distal
      pancreatosplenectomy.

PMID- 24018598
TI  - Synchronous triple cancers of the pancreas, stomach, and cecum treated with S-1
      followed by pancrelipase treatment of pancreatic exocrine insufficiency.
AB  - CONTEXT: Pancreatic cancer is frequently complicated by malignancies in other
      organs. However, synchronous triple cancers including pancreatic cancer have been
      seldom reported in the English language literature. CASE REPORT: We describe the
      rare case of a 77-year-old man with triple cancers of the pancreas, stomach, and
      cecum. Biopsies revealed that all three tumors were adenocarcinomas. The
      pancreatic and gastric tumors were positive for cytokeratin 7 and negative for
      cytokeratin 20, whereas the cecal tumor was negative for cytokeratin 7 and
      positive for cytokeratin 20. K-ras mutations were present at codon 12 in the
      pancreatic tumor and at codon 13 in the cecal tumor, but were absent from the
      gastric tumor. Since the three tumors had different characteristics, the patient
      was diagnosed with synchronous triple cancers. Because invasive surgery was
      required to remove all three tumors and the patient had risk factors for surgery,
      we elected to treat him with chemotherapy. All three cancers were markedly
      reduced in size by treatment with cycles of 100 mg/day S-1 for 2 weeks, followed
      by a 1-week rest. The patient later developed hypoproteinemia and anasarca, which
      was diagnosed as pancreatic exocrine insufficiency due to pancreatic head cancer.
      Treatment with pancrelipase resulted in dramatic improvements in hypoproteinemia
      and anasarca. CONCLUSIONS: This is the first case report in which S-1 was
      effective in triple cancers of the pancreas, stomach, and cecum. Patients with
      pancreatic head cancer should be monitored for pancreatic exocrine insufficiency.

PMID- 24018599
TI  - An illusive cyst: should my mother have had her surgery?

PMID- 24018600
TI  - Is there a proper type of management for branch-duct intraductal papillary
      mucinous tumors of the pancreas?

PMID- 24018601
TI  - Endoscopic ultrasound guided fine needle aspiration for diagnosis of pancreatic
      tuberculosis.

PMID- 24018602
TI  - Glyphosate applications on arable fields considerably coincide with migrating
      amphibians.
AB  - Glyphosate usage is increasing worldwide and the application schemes of this
      herbicide are currently changing. Amphibians migrating through arable fields may
      be harmed by Glyphosate applied to field crops. We investigated the population
      based temporal coincidence of four amphibian species with Glyphosate from 2006 to
      2008. Depending on a) age- and species-specific main migration periods, b) crop
      species, c) Glyphosate application mode for crops, and d) the presumed DT50 value
      (12 days or 47 days) of Glyphosate, we calculated up to 100% coincidence with
      Glyphosate. The amphibians regularly co-occur with pre-sowing/pre-emerging
      Glyphosate applications to maize in spring and with stubble management prior to
      crop sowing in late summer and autumn. Siccation treatment in summer coincides
      only with early pond-leaving juveniles. We suggest in-depth investigations of
      both acute and long-term effects of Glyphosate applications on amphibian
      populations not only focussed on exposure during aquatic periods but also
      terrestrial life stages. 

PMID- 24018603
TI  - GSK-3beta inhibition preserves naive T cell phenotype in bone marrow
      reconstituted mice.
AB  - Hematopoietic stem cell transplantation (HSCT) is used in the treatment of
      hematologic and nonhematologic disorders. PostHSCT immunologic reconstitution is
      a critical component for successful outcome. Pretransplant conditioning impairs
      thymic function, leading to delayed T cell regeneration. Thymus-independent T
      cell expansion is associated with defective generation of naive T cells and
      memory T cell skewing, resulting in decreased diversity in the T cell repertoire,
      thus attenuating the immune responses and increasing the risk of opportunistic
      infections and leukemia relapse. Wingless (Wnt) signaling has been identified as
      an important regulator of T cell development and function. Activated Wnt
      signaling inhibited differentiation of mature T cells in transgenic mouse models.
      The effect of Wnt activation on T cell regeneration following HSCT was not
      investigated. In this study, we demonstrate that the GSK-3beta inhibitor 6
      bromoindirubin 3'-oxime (BIO) activates Wnt/beta-catenin signaling, elevates the
      proportion of naive T cells, and delays T cell differentiation during homeostatic
      T cell expansion in lymphodepleted mice transplanted with human hematopoietic
      stem cells. In vitro BIO-treatment promoted naive T cell expansion following
      mitogenic stimulation and improved proliferative responses of T cells to
      allogeneic stimuli. Treatment with BIO acts to expand the IL7Ralpha(+) subset of
      naive T cells, suggesting the potential mechanism driving T cell expansion during
      IL-7-dependent T cell proliferation. BIO downregulated expression of genes
      activated during effector cell differentiation and preserved naive T cell gene
      expression. We propose that administration of GSK-3beta inhibitor increases the
      potency of T cells in recipients of HSCT by expansion of naive T cell subsets
      with a diverse T cell receptor repertoire.

PMID- 24018604
TI  - UV-induced cis-trans isomerization of zearalenone in contaminated maize.
AB  - In the literature, it has been shown that the naturally occurring trans
      zearalenone (ZEN) is transformed by ultraviolet irradiation to cis-ZEN. However,
      the practical relevance of this transformation in animal feeding remains unclear.
      The aim of the present preliminary investigation was to examine the effect of UV
      irradiation on the concentration of trans-ZEN in a natural feed matrix at
      different dry matter contents to simulate the dry and wet feeding techniques
      usually applied in pig feeding. Four variants, air dry or wet ZEN-contaminated
      ground maize either irradiated or not were tested and analysed with conventional
      HPLC-FLD for trans-ZEN changes, which were further examined for cis-ZEN formation
      by HPLC-MS/MS. In conclusion, it could be shown that, under the investigated wet
      feed conditions, naturally occurring trans-ZEN was partially converted by
      ultraviolet irradiation to its cis counterpart. In contrast, the cis/trans
      isomerization seemed not to be relevant in dry maize. The consequence of this
      finding for practical liquid feeding systems for pigs requires further
      investigation. Additionally, an improvement of the analytical method for cis-ZEN
      determination is needed. 

PMID- 24018605
TI  - Test characteristics of the aldosterone-to-renin ratio as a screening test for
      primary aldosteronism.
AB  - BACKGROUND: The aldosterone-to-renin ratio (ARR) is a widely used screening test
      for primary aldosteronism. Current guidelines recommend a cut-off value of 91 
      pmol/mU. Studies on its sensitivity, specificity, reproducibility and the role of
      medication have been conflicting. We prospectively assessed the test
      characteristics of the ARR and the effect of combination antihypertensive
      treatment. METHODS: In 178 patients with persistent hypertension despite the use
      of at least two antihypertensives, plasma renin and aldosterone were assessed
      twice within an interval of 4 weeks. All patients underwent an intravenous salt
      loading test. A posttest plasma aldosterone exceeding 235  pmol/l was considered
      diagnostic for primary aldosteronism. ARR was repeated after 4 weeks of
      standardized treatment with a calcium channel blocker and/or alpha-adrenergic
      receptor blocker. RESULTS: The prevalence of primary aldosteronism was 15.2%. The
      median ARR was 35.0 (interquartile range 16.2-82.0) in primary aldosteronism
      versus 7.1 (2.2-17.5) pmol/mU in essential hypertensive patients (P < 0.001).
      Under random medication, the ARR had 22.2% sensitivity and 98.7% specificity. On
      standardized treatment, the ARR rose from 9.6 (2.5-24.8) to 21.4 (10.8-52.1) (P <
      0.001). Multivariate regression showed that angiotensin-converting enzyme (ACE)
      inhibitors and angiotensin II-receptor blockers were responsible for the lower
      ARR during random treatment. The area under the receiver operating characteristic
      curve was, however, similar under random and standardized treatment (84 vs. 86%,
      respectively, P = 0.314). Bland-Altman plots showed an almost five-fold
      difference in ARR values taken under the same conditions. CONCLUSION: ARR
      sensitivity for primary aldosteronism is low when the recommended cut-off is
      used. Reproducibility is also poor, stressing the need for alternative screening
      tests.

PMID- 24018606
TI  - Rotigotine for anxiety during wearing-off in Parkinson's disease with dementia.
AB  - BACKGROUND: Wearing-off (WO) refers to the exacerbation of motor and/or non-motor
      symptoms of Parkinson's disease at the end of dose of dopaminergic medications.
      Treatment of WO is based on modifying drug schedule, meal timetable and/or
      increasing dopamine replacement therapy. In advanced and/or demented patients,
      management of WO is often limited by scarce compliance and by cognitive,
      psychiatric and dysautonomic side-effects that may accompany increased
      dopaminergic stimulation. METHODS: Here, we report 2 patients suffering from
      Parkinson's disease with dementia, who experienced anxiety as non-motor symptom
      of WO under stable levodopa therapy. In both cases, transdermal rotigotine (4
      mg/day) was added to the original dopaminergic therapy. RESULTS: Rotigotine
      proved beneficial on symptoms of anxiety in both patients, without worsening
      cognitive and behavioral symptoms. During the 9-month follow-up period, there was
      a slight improvement of motor impairment, with no worsening of drug-related
      dyskinesia. CONCLUSIONS: These preliminary results suggest that rotigotine at low
      dose might improve non-motor symptoms of WO in elderly patients suffering from
      Parkinson's disease with dementia, without raising major safety issues.

PMID- 24018608
TI  - Biodegradable implants efficiently deliver combination of paclitaxel and
      temozolomide to glioma C6 cancer cells in vitro.
AB  - The delivery of local chemotherapy using polymeric implants is a promising anti
      glioma strategy, but a high drug loading rate can lead to a problematic initial
      burst of drug and subsequent neurotoxicity. In this study, we designed and
      fabricated a biodegradable implant for the local delivery of combined paclitaxel
      and temozolomide (TMZ) with low drug loading rates. Paclitaxel-loaded Ca-alginate
      microparticles were formed using an emulsifying-solvent evaporation process.
      Polypropylene carbonate and different weights of TMZ were then added to the
      emulsion. An electrospinning process was used to form fibers that consisted of a
      beads-in-string structure. Using this approach, we achieved with the TMZ +
      paclitaxel fibers a paclitaxel loading rate of 2.1%, with a reduced initial burst
      of drug and prolonged release time compared to the paclitaxel-loaded
      microparticles alone. The TMZ loading rates of fibers with TMZ:paclitaxel ratios
      of 1:2, 1:1, or 2:1 (by manufacturing weight) were 1.2, 2.3, and 4.1%,
      respectively. A cytotoxicity assay suggested that glioma C6 cells were more
      sensitive to the TMZ + paclitaxel fibers compared to either agent alone.
      Cytotoxicity assay also showed that optimal synergistic effect was achieved when
      the weight ratio of the two drugs was 1:1.

PMID- 24018609
TI  - An experimental investigation of the hemodynamic variations due to aplastic
      vessels within three-dimensional phantom models of the circle of Willis.
AB  - A complete circle of Willis (CoW) is found in approximately 30-50% of the
      population. Anatomical variations, such as absent or surgically clamped vessels,
      can result in undesirable flow patterns. These can affect the brain's ability to
      maintain cerebral perfusion and the formation of cerebral aneurysms. An
      experimental test system was developed to simulate cerebral physiological
      conditions through three flexible 3D patient-specific models of complete and
      incomplete CoW geometries. Flow visualizations were performed with isobaric dyes
      and the mapped dye streamlines were tracked throughout the models. Three to seven
      flow impact locations were observed for all configurations, corresponding to
      known sites for aneurysmal formation. Uni and bi-directional cross-flows occurred
      along the communicating arteries. The greatest shunting of flow occurred for a
      missing pre-communicating anterior (A1) and posterior (P1) cerebral arteries. The
      anterior cerebral arteries had the greatest reduction (15-37%) in efferent flow
      rates for missing either a unilateral A1 or bilateral P1 segments. The bi
      directional cross-flows, with multiple afferent flow mixing, observed along the
      communicating arteries may explain the propensity of aneurysm formation at these
      sites. Reductions in efferent flow rates due to aplastic vessel configurations
      may affect normal brain function. 

PMID- 24018610
TI  - Fingerprinting the oxidation state of U(iv) by emission spectroscopy.
AB  - The solid-state structure of the known complex [Et4N][U(NCS)5(bipy)2] has been re
      determined and a detailed spectroscopic and magnetic study has been performed in
      order to confirm the oxidation states of both metal and bipy ligand. Electronic
      absorption and infrared spectroscopy suggest that the uranium is in its +4
      oxidation state and this has been corroborated by emission spectroscopy and
      variable temperature magnetic measurements, as well as theoretical calculations.
      Therefore the bipy ligands are neutral, innocent ligands and not, as would be
      inferred from just a solid state structure, radical anions. 

PMID- 24018607
TI  - A physiological perspective on the use of imaging to assess the in vivo delivery
      of therapeutics.
AB  - Our goal is to provide a physiological perspective on the use of imaging to
      optimize and monitor the accumulation of nanotherapeutics within target tissues,
      with an emphasis on evaluating the pharmacokinetics of organic particles.
      Positron emission tomography (PET), magnetic resonance imaging (MRI) and
      ultrasound technologies, as well as methods to label nanotherapeutic constructs,
      have created tremendous opportunities for preclinical optimization of
      therapeutics and for personalized treatments in challenging disease states.
      Within the methodology summarized here, the accumulation of the construct is
      estimated directly from the image intensity. Particle extravasation is then
      estimated based on classical physiological measures. Specifically, the transport
      of nanotherapeutics is described using the concept of apparent permeability,
      which is defined as the net flux of solute across a blood vessel wall per unit
      surface area of the blood vessel and per unit solute concentration difference
      across the blood vessel wall. The apparent permeability to small molecule MRI
      constructs is accurately shown to be far larger than that estimated for proteins
      such as albumin or nanoconstructs such as liposomes. Further, the quantitative
      measurements of vascular permeability are shown to facilitate detection of the
      transition from a pre-malignant to a malignant cancer and to quantify the
      delivery enhancement resulting from interventions such as ultrasound. While PET
      based estimates facilitate quantitative comparisons of many constructs, high
      field MRI proves useful in the visualization of model drugs within small lesions
      and in the evaluation of the release and intracellular trafficking of
      nanoparticles and cargo. 

PMID- 24018611
TI  - Cognitive behavioural therapies for fibromyalgia.
AB  - BACKGROUND: Fibromyalgia (FM) is a clinically well-defined chronic condition of
      unknown aetiology characterized by chronic widespread pain that often co-exists
      with sleep disturbances, cognitive dysfunction and fatigue. Patients often report
      high disability levels and negative mood. Psychotherapies focus on reducing key
      symptoms, improving daily functioning, mood and sense of personal control over
      pain. OBJECTIVES: To assess the benefits and harms of cognitive behavioural
      therapies (CBTs) for treating FM at end of treatment and at long-term (at least
      six months) follow-up. SEARCH METHODS: We searched the Cochrane Central Register
      of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8), MEDLINE
      (1966 to 28 August 2013), PsycINFO (1966 to 28 August 2013) and SCOPUS (1980 to
      28 August 2013). We searched http://www.clinicaltrials.gov (web site of the US
      National Institutes of Health) and the World Health Organization Clinical Trials
      Registry Platform (ICTRP) (http://www.who.int/ictrp/en/) for ongoing trials (last
      search 28 August,2013), and the reference lists of reviewed articles. SELECTION
      CRITERIA: We selected randomised controlled trials of CBTs with children,
      adolescents and adults diagnosed with FM. DATA COLLECTION AND ANALYSIS: The data
      of all included studies were extracted and the risks of bias of the studies were
      assessed independently by two review authors. Discrepancies were resolved by
      discussion. MAIN RESULTS: Twenty-three studies with 24 study arms with CBTs were
      included. A total of 2031 patients were included; 1073 patients in CBT groups and
      958 patients in control groups. Only two studies were without any risk of bias.
      The GRADE quality of evidence of the studies was low. CBTs were superior to
      controls in reducing pain at end of treatment by 0.5 points on a scale of 0 to 10
      (standardised mean difference (SMD) - 0.29; 95% confidence interval (CI) -0.49 to
      -0.17) and by 0.6 points at long-term follow-up (median 6 months) (SMD -0.40; 95%
      CI -0.62 to -0.17); in reducing negative mood at end of treatment by 0.7 points
      on a scale of 0 to 10 (SMD - 0.33; 95% CI -0.49 to -0.17) and by 1.3 points at
      long-term follow-up (median 6 months) (SMD -0.43; 95% CI -0.75 to -0.11); and in
      reducing disability at end of treatment by 0.7 points on a scale of 0 to 10 (SMD 
      0.30; 95% CI -0.51 to -0.08) and at long-term follow-up (median 6 months) by 1.2
      points (SMD -0.52; 95% CI -0.86 to -0.18). There was no statistically significant
      difference in dropout rates for any reasons between CBTs and controls (risk ratio
      (RR) 0.94; 95% CI 0.65 to 1.35). AUTHORS' CONCLUSIONS: CBTs provided a small
      incremental benefit over control interventions in reducing pain, negative mood
      and disability at the end of treatment and at long-term follow-up. The dropout
      rates due to any reason did not differ between CBTs and controls.

PMID- 24018612
TI  - Cytotoxic activity of gemcitabine, alone or in combination with mitotane, in
      adrenocortical carcinoma cell lines.
AB  - We aimed at investigating in vitro the cytotoxic activity (determined using WST
      1, apoptosis and cell cycle assays) of gemcitabine, alone or in combination with
      mitotane, in mitotane-sensitive H295R and mitotane-insensitive SW-13 cells.
      Results of these experiments were compared with drug-induced modulation of RRM1
      gene, the specific target of gemcitabine. In H295R cells, mitotane and
      gemcitabine combinations showed antagonistic effects and interfered with the
      gemcitabine-mediated inhibition of the S phase of the cell cycle. By contrast, in
      SW-13 cells, except when mitotane was sequentially administered prior to
      gemcitabine, the combination of the two drugs was synergistic. Such opposite
      effects were associated with opposite expression profiles of the target gene,
      with significant up-modulation in H295R but not in SW-13 under gemcitabine and
      mitotane combination treatment. 

PMID- 24018613
TI  - Effect of a multipayer patient-centered medical home on health care utilization
      and quality: the Rhode Island chronic care sustainability initiative pilot
      program.
AB  - IMPORTANCE: The patient-centered medical home is advocated to reduce health care
      costs and improve the quality of care. OBJECTIVE: To evaluate the effects of the
      pilot program of a multipayer patient-centered medical home on health care
      utilization and quality. DESIGN: An interrupted time series design with
      propensity score-matched comparison practices, including multipayer claims data
      from 2 years before (October 1, 2006-September 30, 2008) and 2 years after
      (October 1, 2008-September 30, 2010) the launch of the pilot program. Uptake of
      the intervention was measured with audit data from the National Committee for
      Quality Assurance patient-centered medical home recognition process. SETTING Five
      independent primary care practices and 3 private insurers in the Rhode Island
      Chronic Care Sustainability Initiative. PARTICIPANTS: Patients in 5 pilot and 34
      comparison practices. INTERVENTIONS: Financial support, care managers, and
      technical assistance for quality improvement and practice transformation. MAIN
      OUTCOMES AND MEASURES: Hospital admissions, emergency department visits, and 6
      process measures of quality of care (3 for diabetes mellitus and 3 for colon,
      breast, and cervical cancer screening). RESULTS: The mean National Committee for
      Quality Assurance recognition scores of the pilot practices increased from 42 to
      90 points of a possible 100 points. The pilot and comparison practices had
      statistically indistinguishable baseline patient characteristics and practice
      patterns, except for higher numbers of attributed member months per year in the
      pilot practices (31,130 per practice vs 14,779, P = .01) and lower rates of
      cervical cancer screening in the comparison practices. Although estimates of the
      emergency department visits and inpatient admissions of patients in the pilot
      practices trended toward lower utilization, the only significant difference was a
      lower rate of ambulatory care sensitive emergency department visits in the pilot
      practices. The Chronic Care Sustainability Initiative pilot program was
      associated with a reduction in ambulatory care-sensitive emergency department
      visits of approximately 0.8 per 1000 member months or approximately 11.6%
      compared with the baseline rate of 6.9 for emergency department visits per 1000
      member months (P = .002). No significant improvements were found in any of the
      quality measures. CONCLUSION AND RELEVANCE: After 2 years, a pilot program of a
      patient-centered medical home was associated with substantial improvements in
      medical home recognition scores and a significant reduction in ambulatory care
      sensitive emergency department visits. Although not achieving significance, there
      were downward trends in emergency department visits and inpatient admissions.

PMID- 24018614
TI  - The concurrent validity between leptin, BMI and skin folds during pregnancy and
      the year after.
AB  - BACKGROUND: From a public health perspective it is important to know which of the
      currently used methods to estimate changes in maternal body fat during pregnancy
      and the year thereafter is the most adequate. OBJECTIVES: To evaluate the
      concurrent validity between leptin and surrogates of fat measures: body mass
      index (BMI) and the sum of four skin folds. DESIGN: Data from the New Life(style)
      intervention study were analysed as a cohort study. SETTING: Midwife practices in
      The Netherlands. POPULATION: Healthy pregnant nulliparous women. METHODS:
      Anthropometric measurements were done and blood was collected at 15, 25 and 35
      weeks of pregnancy and at 6, 26 and 52 weeks after delivery. Data were used if at
      least 4 out of the 6 measurements were available, leaving 87 women in the
      analyses. Spearman's correlation coefficients between leptin and BMI and between
      leptin and the sum of skin folds were calculated for each time point and for the
      changes between the time points. RESULTS: Correlations between leptin and BMI
      varied from 0.69 to 0.81. Correlations between leptin and the sum of skin folds
      were comparable, varying between 0.65 and 0.81.Correlations between changes in
      leptin and changes in BMI and the sum of skin folds, respectively, were much
      lower compared with cross-sectional correlations. CONCLUSION: Because of the high
      correlation among the three methods and because of the overlapping intervals, all
      methods seem to be equally adequate to estimate changes in maternal body fat
      during pregnancy and the year thereafter.

PMID- 24018615
TI  - Lactobacillus reuteri and Escherichia coli in the human gut microbiota may
      predict weight gain associated with vancomycin treatment.
AB  - BACKGROUND: Antibiotics, used for 60 years to promote weight gain in animals,
      have been linked to obesity in adults and in children when administered during
      early infancy. Lactobacillus reuteri has been linked to obesity and weight gain
      in children affected with Kwashiorkor using ready-to-use therapeutic food. In
      contrast, Escherichia coli has been linked with the absence of obesity. Both of
      these bacteria are resistant to vancomycin. OBJECTIVES AND METHODS: We assessed
      vancomycin-associated weight and gut microbiota changes, and tested whether
      bacterial species previously linked with body mass index (BMI) predict weight
      gain at 1 year. All endocarditis patients treated with vancomycin or amoxicillin
      in our center were included from January 2008 to December 2010. Bacteroidetes,
      Firmicutes, Lactobacillus and Methanobrevibacter smithii were quantified using
      real-time PCR on samples obtained during the 4-6 weeks antibiotic regimen. L.
      reuteri, L. plantarum, L. rhamnosus, Bifidobacterium animalis and E. coli were
      quantified on stool samples obtained during the first week of antibiotics.
      RESULTS: Of the193 patients included in the study, 102 were treated with
      vancomycin and 91 with amoxicillin. Vancomycin was associated with a 10% BMI
      increase (odds ratio (OR) 14.1; 95% confidence interval (CI; 1.03-194); P=0.047)
      and acquired obesity (4/41 versus 0/56, P=0.01). In patients treated with
      vancomycin, Firmicutes, Bacteroidetes and Lactobacillus increased, whereas M.
      smithii decreased (P<0.05). The absence of E. coli was an independent predictor
      of weight gain (OR=10.7; 95% CI (1.4-82.0); P=0.02). Strikingly, a patient with
      an 18% BMI increase showed a dramatic increase of L. reuteri but no increase of
      E. coli. CONCLUSION: The acquired obesity observed in patients treated with
      vancomycin may be related to a modulation of the gut microbiota rather than a
      direct antibiotic effect. L. reuteri, which is resistant to vancomycin and
      produces broad bacteriocins, may have an instrumental role in this effect.

PMID- 24018618
TI  - Development of multidisciplinary committees for decision making and care
      management in hereditary colon cancer: the French state of the art.
AB  - Multidisciplinary Committees (MDC) in France were established by the Institut
      National du Cancer for the management of therapeutic cancer treatment. We wanted
      to know if this approach is being utilized in Cancer Genetics, in particular for
      patients with a digestive cancer predisposition. A questionnaire was sent to the
      33 French oncogenetic centers. Responses were received from all clinics. We found
      that 76 % of centers regularly use MDCs for the management of hereditary
      digestive cancers. Familial colon cancer cases were the most common situation, in
      which MDCs were utilized. Participation of various medical specialists was
      reported as follows: geneticists (100 %), gastroenterologists (76 %), genetic
      counselors (84 %), surgeons (32 %), and biologists (36 %). Twenty percent of
      centers consult MDCs for every patient compared to 80 % of centers that use MDCs
      only for select cases. MDCs represent a multidisciplinary approach for patients
      affected by inherited cancers and may optimize follow-up for genetic screening
      and further care management. 

PMID- 24018616
TI  - Knockdown of maternal homeobox transcription factor SEBOX gene impaired early
      embryonic development in porcine parthenotes.
AB  - A number of germ cell-specific transcription factors essential for ovarian
      formation and folliculogenesis have been identified and studied. However, the
      role of these factors during early embryonic development has been poorly
      explored. In the present study, we investigated the role of SEBOX, a maternal
      homeobox transcription factor, during early embryonic development in porcine
      parthenotes. mRNA for SEBOX is preferentially expressed in oocytes, and
      expression persists until embryonic genome activation (EGA). Knockdown of SEBOX
      by siRNA disrupted early embryonic development, but not oocyte maturation. Many
      maternal genes essential for early embryonic development were upregulated in
      SEBOX-depleted embryos. Moreover, some pluripotency-associated genes, including
      SOX2 and NANOG, were upregulated when SEBOX was knocked down. Therefore, our data
      demonstrate that SEBOX is required for early embryonic development in pigs and
      appears to regulate the degradation of maternal transcripts and the expression of
      pluripotency genes. 

PMID- 24018619
TI  - Knowledge and attitudes towards genetic testing in those affected with
      Parkinson's disease.
AB  - Advances in genetic tests provide valuable information for clinicians and
      patients around risks and inheritance of Parkinson's Disease (PD); however,
      questions arise whether those affected or at risk of PD will want genetic
      testing, particularly given that there are no preventive or disease-modifying
      therapies currently available. This study sought to determine knowledge and
      attitudes toward genetic testing for those affected with PD. A cross-sectional
      study was undertaken using a standardized questionnaire with six multi-choice
      genetic knowledge and 17 multi-choice attitude items. Participants were selected
      from a registry of people affected with PD living in Queensland, Australia. Half
      of the selected index cases had a family history of PD. Ordinal regression was
      used to evaluate the association between support for genetic testing and
      demographic, knowledge, and other attitudinal factors. The level of genetic
      knowledge was relatively low (37 % correct responses). The vast majority
      supported diagnostic testing (97 %) and 90 % would undertake a genetic test
      themselves. Support for predictive was lower (78 %) and prenatal genetic testing
      had the least support (58 %). Benefits of testing were identified as the ability
      to know the child's risk, seek therapies, and helping science with finding a
      cure. Concerns about genetic testing included potential emotional reactions and
      test accuracy. Genetic knowledge was not significantly associated with attitudes
      towards genetic testing. Patients with PD have strong interest in genetic testing
      for themselves with support for diagnostic testing but less support for
      predictive and prenatal testing. Genetic knowledge was unrelated to testing
      attitudes. 

PMID- 24018620
TI  - Exploration of the perceptions, barriers and drivers of pharmacogenomics practice
      among hospital pharmacists in Adelaide, South Australia.
AB  - There is little literature regarding the barriers to the uptake of
      pharmacogenomics (PG) in pharmacy practice, especially with respect to Australia.
      To date, pharmacists have seldom been engaged in discussions of these issues.
      This study aimed to obtain an in-depth understanding of these barriers by
      interviewing pharmacists in Adelaide, South Australia. Ethics approved
      semistructured interviews were carried out with 21 public hospital pharmacists.
      Analysis of the data identified themes including: confidence to engage in PG,
      clinician acceptance of a pharmacist PG role, and the importance of timely and
      relevant PG education. Interviewees thought that pharmacists could have a greater
      participation in PG in the future, but they questioned whether this would be
      possible at the moment given, among other factors, existing time and work
      constraints. 

PMID- 24018622
TI  - Interpreting the clinical utility of a pharmacogenomic marker based on
      observational association studies.
AB  - It is increasingly recognized that the clinical utility of a pharmacogenomic
      marker is a fundamental characteristic influencing the likelihood of successful
      clinical translation. Although appropriately designed and executed randomized
      controlled trials generally provide the most valid evidence for the clinical
      utility of a pharmacogenomic marker, such evidence may not always be available.
      Observational pharmacogenomic association studies are a common form of evidence
      available, but the assessment of clinical utility based on such evidence is often
      not straightforward. This paper aims to provide insight into this issue using a
      range of illustrative examples. 

PMID- 24018621
TI  - Ethnicity-specific pharmacogenetics: the case of warfarin in African Americans.
AB  - Using a derivation cohort (N=349), we developed the first warfarin dosing
      algorithm that includes recently discovered polymorphisms in VKORC1 and CYP2C9
      associated with warfarin dose requirement in African Americans (AAs). We tested
      our novel algorithm in an independent cohort of 129 AAs and compared the dose
      prediction to the International Warfarin Pharmacogenetics Consortium (IWPC)
      dosing algorithms. Our algorithm explains more of the phenotypic variation
      (R(2)=0.27) than the IWPC pharmacogenomics (R(2)=0.15) or clinical (R(2)=0.16)
      algorithms. Among high-dose patients, our algorithm predicted a higher proportion
      of patients within 20% of stable warfarin dose (45% vs 29% and 2% in the IWPC
      pharmacogenomics and clinical algorithms, respectively). In contrast to our novel
      algorithm, a significant inverse correlation between predicted dose and percent
      West African ancestry was observed for the IWPC pharmacogenomics algorithm among
      patients requiring ?60 mg per week (beta=-2.04, P=0.02). 

PMID- 24018624
TI  - Assessment of pain-related behavior and pro-inflammatory cytokine levels in the
      rat rotator cuff tear model.
AB  - The cause of pain following rotator cuff tear has not been fully elucidated. The
      purpose of this study was to evaluate behavior and inflammatory cytokines in a
      rat unstabilized rotator cuff defect (UCD) model. Forty-five Sprague-Dawley rats
      were divided into three groups: sham; UCD; and stabilized rotator cuff defect
      (SCD). Gait analysis was examined using CatWalk. Tumor necrosis factor (TNF)
      alpha, interleukin(IL)-1beta, and IL-6 were measured within the subacromial bursa
      and the glenohumeral joint synovium at 21 and 56 days after surgery using an
      enzyme-linked immunosorbent assay (ELISA). Stride length, print area and contact
      intensity in the UCD group was significantly lower than in the sham group after
      surgery. Stride length, print area and contact intensity in the SCD group was
      significantly higher than in the UCD group. In contrast, TNF-alpha, IL-1beta, and
      IL-6 in the UCD group was significantly higher than in the sham group at days 21
      and 56. However, TNF-alpha, IL-1beta, and IL-6 in the SCD group was significantly
      lower than in the UCD group at days 21 and 56. The present results suggest that
      SCD is effective not only in improving shoulder function but also in reducing
      inflammatory cytokines, which may serve as one source of pain due to rotator cuff
      tear.

PMID- 24018623
TI  - Lenalidomide as a disease-modifying agent in patients with del(5q)
      myelodysplastic syndromes: linking mechanism of action to clinical outcomes.
AB  - Deletion of the long arm of chromosome 5, del(5q), is the most prevalent
      cytogenetic abnormality in patients with myelodysplastic syndromes (MDS). In
      isolation, it is traditionally associated with favorable prognosis compared with
      other subtypes of MDS. However, owing to the inherent heterogeneity of the
      disease, prognosis for patients with del(5q) MDS is highly variable depending on
      the presence of factors such as additional chromosomal abnormalities, >5 % blasts
      in the bone marrow (BM), or transfusion dependence. Over recent years, the
      immunomodulatory drug lenalidomide has demonstrated remarkable efficacy in
      patients with del(5q) MDS. Advances in the understanding of the pathogenesis of
      the disease have suggested that lenalidomide targets aberrant signaling pathways
      caused by haplosufficiency of specific genes in a commonly deleted region on
      chromosome 5 (e.g., SPARC, RPS14, Cdc25C, and PP2A). As a result, the agent
      specifically targets del(5q) clones while also promoting erythropoiesis and
      repopulation of the bone marrow in normal cells. This review discusses recent
      developments in the understanding of the mechanism of action of lenalidomide, and
      how this underlies favorable outcomes in patients with del(5q) MDS. In addition,
      we discuss how improved understanding of the mechanism of disease will facilitate
      clinicians' ability to predict/monitor response and identify patients at risk of
      relapse.

PMID- 24018625
TI  - An ultrasensitive homogeneous chemiluminescent assay for microRNAs.
AB  - On the basis of a dual-amplification strategy, microRNA (miRNA) hybridization
      amplification by a duplex-specific nuclease (DSN) and signal amplification by a
      DNAzyme, a highly sensitive and selective homogeneous miRNA assay is developed.
      By leveraging on the cumulative and selective nature of the DSN amplification
      process, excellent sensitivity and selectivity are accomplished. 

PMID- 24018626
TI  - Implementation science workshop: an open call for cases for a new JGIM feature
      bridging research and practice.

PMID- 24018627
TI  - Optimizing the involvement of language interpreters during the clinical
      encounter.

PMID- 24018628
TI  - An evaluation of continuity clinic redesign.

PMID- 24018629
TI  - An evaluation of continuity clinic redesign.

PMID- 24018630
TI  - Capsule commentary on Weeks et al., measuring primary care organizational
      capacity for diabetes care coordination: the diabetes care coordination readiness
      assessment.

PMID- 24018632
TI  - Transcranial ultrasound imaging with speed of sound-based phase correction: a
      numerical study.
AB  - This paper presents a numerical study for ultrasound transcranial imaging. To
      correct for the phase aberration from the skull, two critical steps are needed
      prior to brain imaging. In the first step, the skull shape and speed of sound are
      acquired by either CT scans or ultrasound scans. In the ultrasound scan approach,
      phased array and double focusing technique are utilized, which are able to
      estimate the thickness of the skull with a maximum error of around 10% and the
      average speed of sound in the skull is underestimated by less than 2%. In the
      second step, the fast marching method is used to compute the phase delay based on
      the known skull shape and sound speed from the first step, and the computation
      can be completed in seconds for 2D problems. The computed phase delays are then
      used in combination with the conventional delay-and-sum algorithm for generating
      B-mode images. Images of wire phantoms with CT or ultrasound scan-based phase
      correction are shown to have much less artifact than the ones without correction.
      Errors of deducing speed of sound from CT scans are also discussed regarding its
      effect on the transcranial ultrasound images. Assuming the speed of sound grows
      linearly with the density, this study shows that, the CT-based phase correction
      approach can provide clear images of wire phantoms even if the speed of sound is
      overestimated by 400 m s(-1), or the linear coefficient is overestimated by 40%.
      While in this study, ultrasound scan-based phase correction performs almost
      equally well with the CT-based approach, potential problems are identified and
      discussed. 

PMID- 24018633
TI  - Offer and use of complementary and alternative medicine in hospitals of the
      French-speaking part of Switzerland.
AB  - BACKGROUND: In 2004, complementary and alternative medicine (CAM) was offered by
      physicians in one-third of Swiss hospitals. Since then, CAM health policy has
      changed considerably. This study aimed to describe the present supply and use of
      CAM in hospitals in the French-speaking part of Switzerland, and to explore
      qualitatively the characteristics of this offer. METHODS: Between June 2011 and
      March 2012, a short questionnaire was sent to the medical directors of hospitals
      (n = 46), asking them whether CAM was offered, where and by whom. Then, a semi
      directive interview was conducted with ten CAM therapists. RESULTS: Among 37
      responses (return rate 80%), 19 medical directors indicated that their hospital
      offered at least one CAM and 18 reported that they did not. Acupuncture was the
      most frequently available CAM, followed by manual therapies, osteopathy and
      aromatherapy. The disciplines that offered CAM most frequently were
      rehabilitation, gynaecology and obstetrics, palliative care, psychiatry, and
      anaesthetics. In eight out of ten interviews, it appeared that the procedures for
      introducing a CAM in the hospital were not tightly supervised by the hospital and
      were mainly based on the goodwill of the therapists, rather than
      clinical/scientific evidence. CONCLUSION: The number of hospitals offering CAM in
      the French-speaking part of Switzerland seemed to have risen since 2004. The
      selection of a CAM to be offered in a hospital should be based on the same
      procedure of evaluation and validation as conventional therapy, and if the safety
      and efficiency of the CAM is evidence-based, it should receive the same resources
      as a conventional therapy.

PMID- 24018634
TI  - Submuscular bridge plating for length-unstable, pediatric femur fractures.
AB  - BACKGROUND: Submuscular bridge plating has become an acceptable method of
      treatment for pediatric femur fractures. The purpose of our study was to describe
      a technique for submuscular bridge plating and review a series of consecutive,
      length-unstable, pediatric femur fractures treated at a single institution with
      this technique. METHODS: We performed a query of hospital records from January 4,
      2006, to May 10, 2011, to identify length-unstable femur fractures treated with
      submuscular bridge plating by 5 pediatric surgeons. Included were patients
      treated with submuscular bridge plating for a femur fracture. Excluded were
      patients with incomplete medical records, inadequate radiographs, or follow-up <6
      months duration. Fifty-one patients met diagnostic criteria; 19 patients were
      excluded due to incomplete medical records and/or radiographs. RESULTS: The study
      cohort included 32 patients with 33 femur fractures. There were 15 left femurs
      and 18 right femurs, including 1 bilateral fracture patient. Fracture pattern was
      composed of 13 comminuted, 5 spiral, 9 long oblique, and 6 short oblique.
      Mechanisms of injury included: fall from height (8), recreation (23), and MVA
      (2). Mean time for full weightbearing was 8.1 weeks (range, 3 to 17.6 wk). All
      patients were radiographically healed by their 12-week assessment. There were no
      intraoperative complications. Implant removal occurred in 26 patients. There were
      2 cases of a broken screw discovered upon implant removal. The remnant screw was
      not removed in either case. The mean follow-up time for those with implant
      removal was 43.6 weeks (range, 27 to 83 wk). The 11 patients without implant
      removal had a mean follow-up time of 38.6 weeks (range, 31.6 to 50 wk). There
      were no cases of varus or valgus malalignment >10 degrees. One patient
      experienced implant irritation. There were no cases of wound infections.
      CONCLUSIONS: Our technique of surgical intervention has simplified both
      implantation and removal, and produced comparable and excellent healing rates,
      low complication rates, and early return to full weightbearing. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 24018635
TI  - On objective: based education, objectivity, and rater cognition.

PMID- 24018636
TI  - Chinese herbal medicine for atopic eczema.
AB  - BACKGROUND: Chinese herbal medicine (CHM) has been increasingly used for atopic
      eczema. A previous version of this Cochrane review published in 2004 found some
      evidence of a possible benefit for oral ingestion of CHM for eczema, but the
      results were inconclusive and the evidence needs to be updated. We have expanded
      the scope of this review to include an assessment of the topical and oral effects
      of CHM for eczema. OBJECTIVES: To assess the effects of oral ingestion and
      topical applications of CHM for the management of eczema in children and adults.
      SEARCH METHODS: We searched the following databases up to September 2012: the
      Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012,
      Issue 8), MEDLINE (from 1946), EMBASE (from 1974), AMED (from 1985), LILACS (from
      1982), and CINAHL (from 1981). We searched the following from inception: SCOPUS,
      HERBMED, ProQuest, CQVIP, CNKI, and Wanfang Data. We also searched trials
      registers, handsearched conference proceedings, checked the reference lists of
      all included and excluded studies and review articles for further references to
      relevant trials, and contacted experts in Chinese medicine for unpublished
      studies. SELECTION CRITERIA: All randomised controlled trials (RCTs) in children
      and adults with eczema comparing CHM to placebo; no intervention; active
      controls, including acupuncture; or conventional medicines. DATA COLLECTION AND
      ANALYSIS: Two authors selected the RCTs, extracted data, and assessed quality
      independently. We contacted study authors for missing data. We collected adverse
      events from the included studies. MAIN RESULTS: We included 28 studies, with a
      total of 2306 participants. We assessed most of the studies at high 'risk of
      bias', particularly in blinding of participants and personnel, and there was
      substantial inconsistency between studies, so any positive effect of CHM must be
      treated with caution. We did not include the four studies from the previous
      version in this review, because they investigated a CHM product that has been
      withdrawn from the market since 2004.Four studies (three oral and one topical)
      compared CHM to placebo. Pooled data from 2 studies showed the total
      effectiveness rate in the CHM group was higher (by risk ratio (RR) 2.09, 95%
      confidence interval (CI) 1.32 to 3.32; 2 studies; n = 85), and the itching visual
      analogue score (VAS) in the CHM group was 1.53 lower (by standardised mean
      difference (SMD), 95% CI 2.64 to 0.41; 2 Studies; n = 94) than the placebo group,
      where a lower VAS score indicates reduced itch. One study of 85 participants with
      moderate to severe eczema who received an oral CHM formula for 12 weeks reported
      a quality of life (QoL) score 2.5 lower in the CHM group (by difference in means
      (MD), 95% CI 4.77 to 0.23; 1 study; n = 85) than the placebo group, where a lower
      score indicates better QoL.  Twenty-two studies and 1 arm from a study with a 4
      arm parallel controlled design compared CHM (5 oral, 6 topical, and 12 mixed oral
      and topical) to conventional medicines. The total effectiveness rate in the CHM
      groups was superior (RR 1.43, 95% CI 1.27 to 1.61; 21 studies; n = 1868; very low
      quality evidence), and the itching VAS in the CHM groups was 0.83 lower (SMD, 95%
      CI 1.43 to 0.22; 7 studies; n = 465) than the comparators.Two studies compared
      combined oral and topical CHM to the same oral CHM formula alone. The total
      effectiveness rate in 1 study was not statistically significant (RR 1.13, 95% CI
      0.78 to 1.63; 1 study; n = 20). In the other study, the itching VAS in the CHM
      group was 1.05 lower (MD, 95% CI 1.75 to 0.35; 1 study; n = 23) than the control
      group.With regard to side-effects, four studies did not give any report of
      adverse events. The other 24 studies reported minor adverse events, which were
      reversed soon after stopping CHM. One participant withdrew from one trial because
      of exacerbation of their condition after using the CHM intervention.Eight studies
      received government funding. AUTHORS' CONCLUSIONS: We could not find conclusive
      evidence that CHM taken by mouth or applied topically to the skin could reduce
      the severity of eczema in children or adults.Well-designed, adequately powered
      RCTs are needed to evaluate the efficacy and safety of CHM for managing eczema.

PMID- 24018639
TI  - Rolipram improves renal perfusion and function during sepsis in the mouse.
AB  - Microcirculatory dysfunction is correlated with increased mortality among septic
      patients and is believed to be a major contributor to the development of acute
      kidney injury (AKI). Rolipram, a selective phosphodiesterase 4 (PDE4) inhibitor,
      has been shown to reduce microvascular permeability and in the kidney, increase
      renal blood flow (RBF). This led us to investigate its potential to improve the
      renal microcirculation and preserve renal function during sepsis using a murine
      cecal ligation and puncture (CLP) model to induce sepsis. Rolipram, tested at
      doses of 0.3-10 mg/kg i.p., acutely restored capillary perfusion in a bell-shaped
      dose-response effect with 1 mg/kg being the lowest most efficacious dose. This
      dose also acutely increased RBF despite transiently decreasing mean arterial
      pressure. Rolipram also reduced renal microvascular permeability. It is
      noteworthy that delayed treatment with rolipram at 6 hours after CLP restored the
      renal microcirculation, reduced blood urea nitrogen and serum creatinine, and
      increased glomerular filtration rate at 18 hours. However, delayed treatment with
      rolipram did not reduce serum nitrate/nitrite levels, a marker of nitric oxide
      production, nor reactive nitrogen species generation in renal tubules. These data
      show that restoring the microcirculation with rolipram, even with delayed
      treatment, is enough to improve renal function during sepsis despite the
      generation of oxidants and suggest that PDE4 inhibitors should be evaluated
      further for their ability to treat septic-induced AKI. 

PMID- 24018641
TI  - Knockdown of CRM1 inhibits the nuclear export of p27(Kip1) phosphorylated at
      serine 10 and plays a role in the pathogenesis of epithelial ovarian cancer.
AB  - In a previous study, the nuclear export protein chromosomal region maintenance
      (CRM1) was correlated with p27(Kip1) in glioma. The aims of the present study
      were to investigate the expression of CRM1 and pSer10p27 and their functional
      roles in epithelial ovarian cancer (EOC) tissues. Using immunohistochemical
      analysis, CRM1 and pSer10p27 expression levels were shown to be associated with
      histologic stage and grade (P<0.05). High CRM1 and pSer10p27 expression levels
      were prognostic indicators of overall survival (P<0.05). Knockdown of CRM1 and
      pSer10p27 expression arrested cell cycle progression and inhibited the
      proliferation of SKOV3 cells both in vitro and in vivo. These data support the
      idea that pSer10p27 and CRM1 play cooperative roles in EOC.

PMID- 24018640
TI  - Reduction of cocaine self-administration and D3 receptor-mediated behavior by two
      novel dopamine D3 receptor-selective partial agonists, OS-3-106 and WW-III-55.
AB  - Dopamine D3 receptor (D3R)-selective compounds may be useful medications for
      cocaine dependence. In this study, we identified two novel arylamide
      phenylpiperazines, OS-3-106 and WW-III-55, as partial agonists at the D3R in the
      adenylyl cyclase inhibition assay. OS-3-106 and WW-III-55 have 115- and 862-fold
      D3R:D2 receptor (D2R) binding selectivity, respectively. We investigated their
      effects (0, 3, 5.6, or 10 mg/kg) on operant responding by using a multiple
      variable-interval (VI) 60-second schedule that alternated components with sucrose
      reinforcement and components with intravenous cocaine reinforcement (0.375
      mg/kg). Additionally, we evaluated the effect of OS-3-106 (10 mg/kg) on the dose
      response function of cocaine self-administration and the effect of WW-III-55 (0
      5.6 mg/kg) on a progressive ratio schedule with either cocaine or sucrose
      reinforcement. Both compounds were also examined for effects on locomotion and
      yawning induced by a D3R agonist. OS-3-106 decreased cocaine and sucrose
      reinforcement rates, increased latency to first response for cocaine but not
      sucrose, and downshifted the cocaine self-administration dose-response function.
      WW-III-55 did not affect cocaine self-administration on the multiple-variable
      interval schedule, but it reduced cocaine and sucrose intake on the progressive
      ratio schedule. Both compounds reduced locomotion at doses that reduced
      responding, and both compounds attenuated yawning induced by low doses of 7-OH
      DPAT (a D3R-mediated behavior), but neither affected yawning on the descending
      limb of the 7-OH-DPAT dose-response function (a D2R-mediated behavior).
      Therefore, both compounds blocked a D3R-mediated behavior. However, OS-3-106 was
      more effective in reducing cocaine self-administration. These findings support
      D3Rs, and possibly D2Rs, as targets for medications aimed at reducing the
      motivation to seek cocaine. 

PMID- 24018642
TI  - Systematic combination screening reveals synergism between rapamycin and
      sunitinib against human lung cancer.
AB  - Mammalian target of rapamycin (mTOR) acts as a hub integrating signals from
      nutrient availability and growth factors and plays central roles in regulating
      protein synthesis and cell growth, which has been validated as a promising target
      for cancer therapy. Rapamycin and its analogues have emerged as the first
      generation of mTOR inhibitors, but their efficacy is modest in clinical settings.
      Combinatorial use of rapamycin with other drugs is a promising strategy to
      improve its anticancer activity. Here we developed an unbiased systematic binary
      screening platform aiming to discover new remedy for rapamycin-based cancer
      therapy. We found that sunitinib emerged as one of the clinically available
      anticancer drugs screened that displayed significant synergy with rapamycin in
      NSCLC cells. Combination of rapamycin with sunitinib resulted in enhanced cell
      cycle arrest in G1 phase, which was accompanied with enhanced suppression of mTOR
      signaling and disruption of the negative feedback loop that activate AKT upon
      mTORC1 inhibition. Furthermore, sunitinib and rapamycin displayed synergistic
      activity against tube formation by human microvessel endothelial cells as well as
      outgrowth of endothelial tubes and microvessels both in vitro and in vivo, which
      is associated with down-regulation of VEGF secretion and HIF1alpha expression.
      Our study demonstrated that new combinatorial regimen could be identified via
      systematic drug combination screening and established a mechanistic rationale for
      a combination approach using rapalogs and sunitinib in the treatment of human
      NSCLC. 

PMID- 24018643
TI  - A novel orthotopic mouse model of head and neck cancer and lymph node metastasis.
AB  - Prognosis of head and neck squamous cell carcinoma (HNSCC) is largely determined
      by the extent of lymph node (LN) metastasis at diagnosis, and this appears to be
      controlled by cancer cell genetics. To examine the role of these genes in LN
      metastasis, we created a human-in-mouse orthotopic model of HNSCC and performed
      comparative microarray analysis of gene expression between populations of HNSCC
      cell lines derived before and after serial transplantation and in vivo metastasis
      in mice. Microarray analysis comparing the USC-HN3-GFP, USC-HN3-GFP-G1 and USC
      HN3-GFP-G2 cell lines identified overexpression of genes implicated in epithelial
      to- mesenchymal transition and the formation of cancer stem cells, including CAV
      1, TLR-4 (Toll-like receptor 4), MMP-7 (matrix metalloproteinase 7), ALDH1A3, OCT
      4 and TRIM-29. Ingenuity Pathway Analysis confirmed upregulation of respective
      gene signaling pathways in the USC-HN1-GFP-G2 cell line. Patient HNSCC samples
      from advanced stages overexpressed ALDH1A3, CAV-1 and MMP-7. Our results show
      that CAV-1, TLR-4, MMP-7, ALDH1A3, OCT-4 and TRIM-29 have increased expression in
      HNSCC cells selected for an enhanced metastatic phenotype and suggest that these
      genes may have an important role in the metastatic potential of HNSCC cells.
      Inhibition of these genes may therefore have prognostic and therapeutic utility
      in HNSCC. 

PMID- 24018644
TI  - Centrosomal kinase Nek2 cooperates with oncogenic pathways to promote metastasis.
AB  - Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it
      contributes toward tumorigenesis remains poorly understood. dNek2 overexpression
      in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog
      wingless (Wg), and alteration of cell migration markers-Rho1, Rac1 and E-cadherin
      (Ecad)-resulting in changes in cell shape and tissue morphogenesis. dNek2
      overexpression cooperated with receptor tyrosine kinase and mitogen-activated
      protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein
      to promote local invasion, distant seeding and metastasis. In tumor cell
      injection assays, dNek2 cooperated with Ras and Src signaling to promote
      aggressive colonization of tumors into different adult fly tissues. Inhibition of
      the PI3K pathway suppressed the cooperation of dNek2 with other growth pathways.
      Consistent with our fly studies, overexpression of human Nek2 in A549 lung
      adenocarcinoma and HEK293T cells led to activation of the Akt pathway and
      increase in beta-catenin protein levels. Our computational approach identified a
      class of Nek2-inhibitory compounds and a novel drug-like pharmacophore that
      reversed the Nek2 overexpression phenotypes in flies and human cells. Our finding
      posits a novel role for Nek2 in promoting metastasis in addition to its currently
      defined role in promoting chromosomal instability. It provides a rationale for
      the selective advantage of centrosome amplification in cancer. 

PMID- 24018645
TI  - RAS mutation status predicts survival and patterns of recurrence in patients
      undergoing hepatectomy for colorectal liver metastases.
AB  - OBJECTIVE: To determine the impact of RAS mutation status on survival and
      patterns of recurrence in patients undergoing curative resection of colorectal
      liver metastases (CLM) after preoperative modern chemotherapy. BACKGROUND: RAS
      mutation has been reported to be associated with aggressive tumor biology.
      However, the effect of RAS mutation on survival and patterns of recurrence after
      resection of CLM remains unclear. METHODS: Somatic mutations were analyzed using
      mass spectroscopy in 193 patients who underwent single-regimen modern
      chemotherapy before resection of CLM. The relationship between RAS mutation
      status and survival outcomes was investigated. RESULTS: Detected somatic
      mutations included RAS (KRAS/NRAS) in 34 (18%), PIK3CA in 13 (7%), and BRAF in 2
      (1%) patients. At a median follow-up of 33 months, 3-year overall survival (OS)
      rates were 81% in patients with wild-type versus 52.2% in patients with mutant
      RAS (P = 0.002); 3-year recurrence-free survival (RFS) rates were 33.5% with wild
      type versus 13.5% with mutant RAS (P = 0.001). Liver and lung recurrences were
      observed in 89 and 83 patients, respectively. Patients with RAS mutation had a
      lower 3-year lung RFS rate (34.6% vs 59.3%, P < 0.001) but not a lower 3-year
      liver RFS rate (43.8% vs 50.2%, P = 0.181). In multivariate analyses, RAS
      mutation predicted worse OS [hazard ratio (HR) = 2.3, P = 0.002), overall RFS (HR
      = 1.9, P = 0.005), and lung RFS (HR = 2.0, P = 0.01), but not liver RFS (P =
      0.181). CONCLUSIONS: RAS mutation predicts early lung recurrence and worse
      survival after curative resection of CLM. This information may be used to
      individualize systemic and local tumor-directed therapies and follow-up
      strategies.

PMID- 24018647
TI  - Intensive glucose regulation in hyperglycemic acute coronary syndrome: results of
      the randomized BIOMarker study to identify the acute risk of a coronary syndrome
      2 (BIOMArCS-2) glucose trial.
AB  - IMPORTANCE: Elevated plasma glucose levels in patients with acute coronary
      syndrome (ACS) on hospital admission are associated with increased mortality.
      Clinical trials of glucose regulation have provided inconsistent results with
      respect to cardiovascular outcomes, perhaps because target glucose levels have
      been suboptimal. OBJECTIVE: To study the effectiveness and safety of intensive
      glucose management in patients with ACS who have hyperglycemia, aiming at strict
      blood glucose normalization. DESIGN, SETTING, AND PARTICIPANTS: Single-center,
      prospective, open-label, randomized clinical trial in a large teaching hospital.
      Patients with ACS with an admission plasma glucose level of 140 to 288 mg/dL were
      eligible for inclusion and enrolled from July 23, 2008, to February 8, 2012.
      Patients with insulin-dependent diabetes mellitus were excluded. Informed consent
      was obtained from 294 patients, who were randomized. Of these, 93.6% received
      percutaneous coronary intervention (PCI). INTERVENTIONS: Intensive glucose
      management strategy, aiming at a plasma glucose level of 85 to 110 mg/dL by using
      intravenous insulin, or to conventional expectative glucose management. MAIN
      OUTCOMES AND MEASURES: End points were assessed according to the intention-to
      treat principle. The primary end point was high-sensitivity troponin T value 72
      hours after admission (hsTropT72); secondary end points, area under the curve of
      creatine kinase, myocardial band (AUC-CK-MB), release and myocardial perfusion
      scintigraphy findings at 6 weeks' follow-up. RESULTS: In the intensive management
      arm, median hsTropT72 was 1197 ng/L (25th and 75th percentiles of distribution,
      541-2296 ng/L) vs 1354 ng/L (530-3057 ng/L) in the conventional arm (P = .41).
      Median AUC-CK-MB was 2372 U/L (1242-5004 U/L) vs 3171 U/L (1620-5337 U/L) (P =
      .18). The difference in median extent of myocardial injury measured by myocardial
      perfusion scintigraphy was not significant (2% vs 4%) (P = .07). Severe
      hypoglycemia (<50 mg/dL) was rare and occurred in 13 patients. Before discharge,
      death or a spontaneous second myocardial infarction occurred in 8 patients (5.7%)
      vs 1 (0.7%) (P = .04). CONCLUSIONS AND RELEVANCE Intensive glucose regulation did
      not reduce infarct size in hyperglycemic patients with ACS treated with PCI, and
      was associated with harm. Future studies should focus on patients with ACS who
      have persistently elevated blood glucose after PCI, and should evaluate
      alternative strategies for optimizing glycemia. TRIAL REGISTRATION:
      www.trialregister.nl Identifier: NTR1205.

PMID- 24018646
TI  - Can diabetes be surgically cured? Long-term metabolic effects of bariatric
      surgery in obese patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: Evaluate the long-term effects of bariatric surgery on type 2 diabetes
      (T2DM) remission and metabolic risk factors. BACKGROUND: Although the impressive
      antidiabetic effects of bariatric surgery have been shown in short- and medium
      term studies, the durability of these effects is uncertain. Specifically, long
      term remission rates following bariatric surgery are largely unknown. METHODS:
      Clinical outcomes of 217 patients with T2DM who underwent bariatric surgery
      between 2004 and 2007 and had at least 5-year follow-up were assessed. Complete
      remission was defined as glycated hemoglobin (A1C) less than 6% and fasting blood
      glucose (FBG) less than 100 mg/dL off diabetic medications. Changes in other
      metabolic comorbidities, including hypertension, dyslipidemia, and diabetic
      nephropathy, were assessed. RESULTS: At a median follow-up of 6 years (range: 5
      9) after surgery (Roux-en-Y gastric bypass, n = 162; gastric banding, n = 32;
      sleeve gastrectomy, n = 23), a mean excess weight loss (EWL) of 55% was
      associated with mean reductions in A1C from 7.5% +/- 1.5% to 6.5% +/- 1.2% (P <
      0.001) and FBG from 155.9 +/- 59.5 mg/dL to 114.8 +/- 40.2 mg/dL (P < 0.001).
      Long-term complete and partial remission rates were 24% and 26%, respectively,
      whereas 34% improved (>1% decrease in A1C without remission) from baseline and
      16% remained unchanged. Shorter duration of T2DM (P < 0.001) and higher long-term
      EWL (P = 0.006) predicted long-term remission. Recurrence of T2DM after initial
      remission occurred in 19% and was associated with longer duration of T2DM (P =
      0.03), less EWL (P = 0.02), and weight regain (P = 0.015). Long-term control
      rates of low high-density lipoprotein, high low-density lipoprotein, high
      triglyceridemia, and hypertension were 73%, 72%, 80%, and 62%, respectively.
      Diabetic nephropathy regressed (53%) or stabilized (47%). CONCLUSIONS: Bariatric
      surgery can induce a significant and sustainable remission and improvement of
      T2DM and other metabolic risk factors in severely obese patients. Surgical
      intervention within 5 years of diagnosis is associated with a high rate of long
      term remission.

PMID- 24018649
TI  - Mutation of the critical pH-gating residues histidine 231 to glutamate increase
      open probability of outer membrane protein G in planar lipid bilayer.

PMID- 24018650
TI  - Laparoscopic sphincter-preserving surgery (intersphincteric resection) after
      neoadjuvant imatinib treatment for gastrointestinal stromal tumor (GIST) of the
      rectum.
AB  - BACKGROUND: Gastrointestinal stromal tumors (GISTs) of the rectum are rarely
      found, and radical surgery such as abdominoperineal resection would be necessary
      for large rectal GIST. On the other hand, therapy for GIST has changed
      significantly with the use of imatinib. Neoadjuvant imatinib therapy may reduce
      tumor size and may potentially prevent extended surgery. Moreover, when sphincter
      preserving surgery is carried out laparoscopically, it can be performed as
      minimally invasive surgery with preservation of the anus. METHODS: From 2008 to
      2011, five patients with rectal GIST were treated in our hospital. All patients
      received preoperative imatinib treatment (400 mg/day) and underwent laparoscopic
      sphincter-preserving surgery after 4-12 months of this treatment. RESULTS:
      Initial median tumor size was 31 mm (range, 24-88). At the time of operation, the
      median tumor size was 24 mm (range, 11-52). Sphincter-preserving surgery was
      performed in all patients. Three patients underwent laparoscopic intersphincteric
      resection (ISR), and two patients underwent transanal full-thickness local
      resection and recto-anal anastomosis following laparoscopic ISR. Macroscopically
      complete resection was achieved, and microscopically, the resection margin was
      not involved of residual tumors. The median duration of postoperative hospital
      stay was 16 days (range, 13-30). No recurrence occurred in all patients during 1
      to 4 years. CONCLUSIONS: The present study suggests that neoadjuvant imatinib
      therapy might be effective to prevent extended surgery for rectal GIST, and
      laparoscopic sphincter-preserving surgery is safe and technically feasible. We
      recommend a combination of neoadjuvant imatinib therapy and laparoscopic ISR for
      locally advanced rectal GIST.

PMID- 24018651
TI  - Skeletal trauma generates systemic BMP2 activation that is temporally related to
      the mobilization of CD73+ cells.
AB  - The relationship between BMP2 expression and the recruitment of skeletogenic stem
      cells was assessed following bone marrow reaming. BMP2 expression was examined
      using transgenic mice in which beta-galactosidase had been inserted into the
      coding region of BMP2. Stem cell mobilization was analyzed by FACS analysis using
      CD73, a marker associated with bone marrow stromal stem cells. BMP2 expression
      was induced in endosteal lining cells, cortical osteocytes and periosteal cells
      in both the reamed and in contralateral bones. BMP2 mRNA expression in the reamed
      bone showed an early peak within the first 24 h of reaming followed by a later
      peak at 7 days, while contralateral bones only showed the 7 days peak of
      expression. FACS analysis sorting on CD73 positive cells showed a 50% increase of
      these cells at 3 and 14 days in the marrow of the injured bone and a single peak
      at 14 days of the marrow cell population of the contralateral bone. A ~20%
      increase of CD73 positive cells was seen in the peripheral blood 2 days after
      reaming. These data showed that traumatic bone injury caused a systemic induction
      of BMP2 expression and that this increase is correlated with the mobilization of
      CD73 positive cells.

PMID- 24018653
TI  - Abstracts of the Irish Endocrine Society 38th Annual Meeting. November 8-9, 2013.
      Kilkenny, Ireland.

PMID- 24018654
TI  - Abstracts of the 64th Irish Cardiac Society Annual Scientific Meeting. October 4
      5, 2013. Killarney, County Kerry, Ireland.

PMID- 24018655
TI  - A novel technique for VMAT QA with EPID in cine mode on a Varian TrueBeam linac.
AB  - Volumetric modulated arc therapy (VMAT) is a relatively new treatment modality
      for dynamic photon radiation therapy. Pre-treatment quality assurance (QA) is
      necessary and many efforts have been made to apply electronic portal imaging
      device (EPID)-based IMRT QA methods to VMAT. It is important to verify the gantry
      rotation speed during delivery as this is a new variable that is also modulated
      in VMAT. In this paper, we present a new technique to perform VMAT QA using an
      EPID. The method utilizes EPID cine mode and was tested on Varian TrueBeam in
      research mode. The cine images were acquired during delivery and converted to
      dose matrices after profile correction and dose calibration. A sub-arc
      corresponding to each cine image was extracted from the original plan and its
      portal image prediction was calculated. Several analyses were performed including
      3D gamma analysis (2D images + gantry angle axis), 2D gamma analysis, and other
      statistical analyses. The method was applied to 21 VMAT photon plans of 3 photon
      energies. The accuracy of the cine image information was investigated.
      Furthermore, this method's sensitivity to machine delivery errors was studied.
      The pass rate (92.8 +/- 1.4%) for 3D gamma analysis was comparable to those from
      Delta(4) system (99.9 +/- 0.1%) under similar criteria (3%, 3 mm, 5% threshold
      and 2 degrees  angle to agreement) at 6 MV. The recorded gantry angle and
      start/stop MUs were found to have sufficient accuracy for clinical QA. Machine
      delivery errors can be detected through combined analyses of 3D gamma, gantry
      angle, and percentage dose difference. In summary, we have developed and
      validated a QA technique that can simultaneously verify the gantry angle and
      delivered MLC fluence for VMAT treatment.This technique is efficient and its
      accuracy is comparable to other QA methods. 

PMID- 24018656
TI  - A two-dimensional zeolitic imidazolate framework with a cushion-shaped cavity for
      CO2 adsorption.
AB  - A new two-dimensional zeolitic imidazolate framework (named as ZIF-L) was
      synthesized in zinc salt and 2-methylimidazole (Hmim) aqueous solution at room
      temperature. ZIF-L (Zn(mim)2.(Hmim)1/2.(H2O)3/2 or C10H16N5O3/2Zn) has unique
      cushion-shaped cavities and leaf-like crystal morphology, and exhibits excellent
      CO2 adsorption properties.

PMID- 24018658
TI  - Effects of epigallocatechin-3-gallate (EGCG) on A549 lung cancer tumor growth and
      angiogenesis.
AB  - Epigallocatechin 3-gallate (EGCG) has cytotoxic effects in many cancer cells. It
      has been reported that A549 lung cancer cells are markedly resistant to cell
      death induced by EGCG. In the present study, the effects of EGCG on A549 lung
      cancer cell growth and angiogenesis were studied. We found that EGCG dose
      dependently suppressed A549 cell growth, while A549 cells were markedly resistant
      to cell death in vitro. Next we found that EGCG increased endostatin expression
      and suppressed vascular endothelial growth factor (VEGF) expression. We further
      studied to determine whether EGCG would suppress A549 tumor growth in nude mouse
      and angiogenesis. EGCG in drinking water significantly suppressed A549 tumor
      growth in nude mice. Histological analysis revealed that the number of CD34
      positive vessels had a tendency to decrease in the tumor. In sum, EGCG had anti
      proliferative effects of A549 on tumor growth and showed a tendency to suppress
      angiogenesis. 

PMID- 24018659
TI  - Requirement of catalytic-triad and related amino acids for the acyltransferase
      activity of Tanacetum cinerariifolium GDSL lipase/esterase TcGLIP for ester-bond
      formation in pyrethrin biosynthesis.
AB  - We have recently discovered that a GDSL lipase/esterase (TcGLIP) in Tanacetum
      cinerariifolium catalyzed acyltransferase activity to form an ester bond in the
      natural insecticide, pyrethrin. TcGLIP contained Ser40 in Block I, Gly64 in Block
      II, Asn168 in Block III and Asp318 and His321 in Block V, suggesting underlying
      hydrolase activity, although little is known about their role in acyltransferase
      activity. We expressed TcGLIP here in Esherichia coli as a fusion with maltose
      binding protein (MBP), part of the fusion being cleaved with a protease to obtain
      MBP-free TcGLIP. A kinetic analysis revealed that the MBP moiety scarcely
      influenced the kinetic parameters. The effects on acyltransferase activity of
      mutations of Gly64, Asn168, Asp318 and His321 were investigated by using MBP
      fused TcGLIP. Mutations of these amino acids markedly reduced the acyltransferase
      activity, suggesting their critical role in the production of pyrethrins. 

PMID- 24018660
TI  - Induction of ALDH activity in intestinal dendritic cells by Lactobacillus
      plantarum NRIC0380.
AB  - Lactic acid bacteria have been reported to have various immune-regulating
      activities. We also found in the previous study that the oral administration of
      heat-killed Lactobacillus plantarum NRIC0380 induced CD4(+)CD25(+)Foxp3(+) cells
      (Treg cells). We examine in this present study the influence of NRIC0380 on the
      function of intestinal dendritic cells (DCs) in vitro and in vivo. The aldehyde
      dehydrogenase (ALDH) activity was significantly induced in DCs obtained from the
      mesenteric lymph node (MLN) by culturing with NRIC0380. The oral administration
      of NRIC0380 also significantly increased ALDH-positive DCs in MLN. NRIC0380
      significantly enhanced the production of TGF-beta from MLN cells in vitro. These
      effects were not apparent in cells from the Peyer's patch (PP) and spleen (SPL).
      NRIC0380 also significantly enhanced the expression of B7-H1 on DCs of all organs
      in vitro. The effects of NRIC0380 on DCs, especially those located in MLN, might
      be involved in its function to induce Treg cells. 

PMID- 24018661
TI  - Modulation of allosteric regulation by E38K and G101N mutations in the potato
      tuber ADP-glucose pyrophosphorylase.
AB  - The higher plant ADP-glucose (ADPG) pyrophosphorylase (AGPase), composed of two
      small subunits and two large subunits (LSs), produces ADPG, the sole substrate
      for starch biosynthesis from alpha-D-glucose 1-phosphate and ATP. This enzyme
      controls a key step in starch synthesis as its catalytic activity is activated by
      3-phosphoglycerate (3-PGA) and inhibited by orthophosphate (Pi). Previously, two
      mutations in the LS of potato AGPase (PLS), PLS-E38K and PLS-G101N, were found to
      increase sensitivity to 3-PGA activation and tolerance to Pi inhibition. In the
      present study, the double mutated enzyme (PLS-E38K/G101N) was evaluated. In a
      complementation assay of ADPG synthesis in an Escherichia coli mutant defective
      in the synthesis of ADPG, expression of PLS-E38K/G101N mediated higher glycogen
      production than wild-type potato AGPase (PLS-WT) and the single mutant enzymes,
      PLS-E38K and PLS-G101N, individually. Purified PLS-E38K/G101N showed higher
      sensitivity to 3-PGA activation and tolerance to Pi inhibition than PLS-E38K or
      PLS-G101N. Moreover, the enzyme activities of PLS-E38K, PLS-G101N, and PLS
      E38K/G101N were more readily stimulated by other major phosphate-ester
      metabolites, such as fructose 6-phosphate, fructose 2,6-bisphosphate, and ribose
      5-phosphate, than was that of PLS-WT. Hence, although the specific enzyme
      activities of the LS mutants toward 3-PGA were impaired to some extent by the
      mutations, our results suggest that their enhanced allosteric regulatory
      properties and the broadened effector selectivity gained by the same mutations
      not only offset the lowered enzyme catalytic turnover rates but also increase the
      net performance of potato AGPase in vivo in view of increased glycogen production
      in bacterial cells. 

PMID- 24018662
TI  - A thermophilic alkalophilic alpha-amylase from Bacillus sp. AAH-31 shows a novel
      domain organization among glycoside hydrolase family 13 enzymes.
AB  - alpha-Amylases (EC 3.2.1.1) hydrolyze internal alpha-1,4-glucosidic linkages of
      starch and related glucans. Bacillus sp. AAH-31 produces an alkalophilic
      thermophilic alpha-amylase (AmyL) of higher molecular mass, 91 kDa, than typical
      bacterial alpha-amylases. In this study, the AmyL gene was cloned to determine
      its primary structure, and the recombinant enzyme, produced in Escherichia coli,
      was characterized. AmyL shows no hydrolytic activity towards pullulan, but the
      central region of AmyL (Gly395-Asp684) was similar to neopullulanase-like alpha
      amylases. In contrast to known neopullulanase-like alpha-amylases, the N-terminal
      region (Gln29-Phe102) of AmyL was similar to carbohydrate-binding module family
      20 (CBM20), which is involved in the binding of enzymes to starch granules.
      Recombinant AmyL showed more than 95% of its maximum activity in a pH range of
      8.2-10.5, and was stable below 65  degrees C and from pH 6.4 to 11.9. The kcat
      values for soluble starch, gamma-cyclodextrin, and maltotriose were 103 s(-1),
      67.6 s(-1), and 5.33 s(-1), respectively, and the Km values were 0.100 mg/mL,
      0.348 mM, and 2.06 mM, respectively. Recombinant AmyL did not bind to starch
      granules. But the substitution of Trp45 and Trp84, conserved in site 1 of CBM20,
      with Ala reduced affinity to soluble starch, while the mutations did not affect
      affinity for oligosaccharides. Substitution of Trp61, conserved in site 2 of
      CBM20, with Ala enhanced hydrolytic activity towards soluble starch, indicating
      that site 2 of AmyL does not contribute to binding to soluble long-chain
      substrates. 

PMID- 24018663
TI  - Purification and characterization of UDP-arabinopyranose mutase from
      Chlamydomonas reinhardtii.
AB  - Chlamydomonas reinhardtii cells are surrounded by a mixture of hydroxyprolin-rich
      glycoproteins consisting of L-arabinose, D-galactose, D-glucose, and D-mannose
      residues. The L-arabinose residue is thought to be attached by a transfer of UDP
      L-arabinofuranose (UDP-Araf), which is produced from UDP-L-arabinopyranose (UDP
      Arap) by UDP-arabinopyranose mutase (UAM). UAM was purified from the cytosol to
      determine the involvement of C. reinhardtii UAM (CrUAM) in glycoprotein
      synthesis. CrUAM was purified 94-fold to electrophoretic homogeneity by
      hydrophobic and size-exclusion chromatography. CrUAM catalyzed the reversible
      conversion between UDP-Arap and UDP-Araf and exhibited autoglycosylation activity
      when UDP-D-[(14)C]glucose was added as substrate. Compared to the properties of
      native and recombinant CrUAM overexpressed in Escherichia coli, native CrUAM
      showed a higher affinity for UDP-Arap than recombinant CrUAM did. This increased
      affinity for UDP-Arap might have been caused by post-translational modifications
      that occur in eukaryotes but not in prokaryotes. 

PMID- 24018664
TI  - Effects of Lactobacillus gasseri OLL2809 on the induced endometriosis in rats.
AB  - We have reported an inhibitory effect of Lactobacillus gasseri OLL2809 (OLL2809)
      on the growth of mouse endometrial tissue in the abdominal cavity. The present
      study aimed to investigate the efficacy of Lactobacillus gasseri OLL2809
      (OLL2809) on pre-existing endometriosis implanted on the abdominal wall in
      diestrus Wistar-Imamichi female rats. One week after implantation, the volume of
      the endometrial tissue was measured after laparotomy. OLL2809 and dienogest were
      administered for 4 weeks. OLL2809 significantly enhanced the decrease in the
      volume (p<0.01) as compared with control. Complete healing was observed in two of
      nine rats, but in none of the control group. Dienogest did not show significant
      efficacy. These findings suggest that OLL2809 is useful not only in therapy of
      pre-existing endometriosis but also in the prevention of the growth of
      endometrial tissue. 

PMID- 24018665
TI  - Nudix hydrolase controls nucleotides and glycolytic mechanisms in hypoxic
      Aspergillus nidulans.
AB  - Nucleoside diphosphates linked to moiety X (Nudix) hydrolase functions were
      investigated in hypoxic Aspergillus nidulans cells. Among three nudix hydrolase
      isozymes, NdxA transcription was up-regulated under oxygen (O2)-limited
      conditions. A gene disruptant of the NdxA-encoding gene (NdxADelta) accumulated
      more NADH and ADP-ribose than the wild type (WT) under the same conditions. These
      results indicate that NdxA hydrolyzes these nucleotides in hypoxic fungal cells,
      which accords with the thesis that NdxA hydrolyzes NADH and ADP-ribose. Under O2
      limited conditions, NdxADelta decreased glucose consumption, the production of
      ethanol and lactate, cellular ATP levels, and growth as compared with WT. WT
      cultured under hypoxia converted exogenously added fructose 1,6-bisphophate, a
      glycolytic intermediate, to glyceraldehyde 3-phosphate (GAP). The hypoxic
      NdxADelta cells accumulated 3.0- to 4.2-fold more GAP than WT under the same
      conditions, indicating that NdxA increased GAP oxidation by a glycolytic
      mechanism. Steady-state kinetics indicated that NADH and ADP-ribose competitively
      inhibited fungal GAP dehydrogenase (GAPDH) with Ki values of 34- and 55-uM,
      respectively. These results indicate that NdxA hydrolyzes cellular NADH- and ADP
      ribose, derepresses GAPDH activity, and hence up-regulates glycolysis in hypoxic
      A. nidulans cells. That NdxADelta consumed less pyruvate and tricarboxylate cycle
      intermediates than WT suggests that NdxA-dependent hydrolysis of nucleotides
      controls the catabolism of these carbon sources under O2-limited conditions. 

PMID- 24018666
TI  - Purification of porcine hair keratin subunits and their immobilization for use as
      cell culture substrates.
AB  - We purified both the type I subunit and type II subunit of porcine hair keratin
      and compared their ability to form a uniform film of reconstituted keratin on a
      culture plate, and their effect on a model of neural cells. We observed the
      surface of the keratin-immobilized plate using a scanning electron microscope
      (SEM) and measured water contact angles to characterize the surface. We cultured
      PC12 cells on plates on which crude keratin, the type I subunit, or the type II
      subunit were immobilized. The water contact angles were slightly different from
      each other. The cells proliferated well on all three keratin-immobilized plates.
      The type II subunit showed a tendency to inhibit the differentiation of PC12
      cells significantly as an extension of the cell shapes and neurite outgrowth in
      comparison with the crude extract and the type I subunit. The type I subunit and
      the type II subunit showed slight differences in cell differentiation, but not in
      cell proliferation. 

PMID- 24018667
TI  - Effects of conversion of the zinc-binding motif sequence of thermolysin, HEXXH,
      to that of dipeptidyl peptidase III, HEXXXH, on the activity and stability of
      thermolysin.
AB  - Most zinc metalloproteinases have the consensus zinc-binding motif sequence
      HEXXH, in which two histidine residues chelate a catalytic zinc ion. The zinc
      binding motif sequence of thermolysin, H(142)ELTH(146), belongs to this motif
      sequence, while that of dipeptidyl peptidase III (DPP III), H(450)ELLGH(455),
      belongs to the motif sequence HEXXXH. In this study, we examined effects of
      conversion of HEXXH to HEXXXH in thermolysin on its activity and stability.
      Thermolysin variants bearing H(142)ELLGH(146) or H(142)ELTGH(146) (designated
      T145LG and T145TG respectively) were constructed by site-directed mutagenesis and
      were produced in Escherichia coli cells by co-expressing the mature and pro
      domains separately. They did not exhibit hydrolyzing activity for casein or N-[3
      (2-furyl)acryloyl]-glycyl-L-leucine amide, but exhibited binding ability to a
      substrate analog glycyl-D-phenylalanine (Gly-D-Phe). The apparent denaturing
      temperatures based on the ellipticity at 222 nm of T145LG and T145TG were 85 +/-
      1  degrees C and 86 +/- 1  degrees C respectively, almost the same as that of
      wild-type thermolysin (85 +/- 1  degrees C). These results indicate that
      conversion of HEXXH to HEXXXH abolishes thermolysin activity, but does not affect
      its binding ability to Gly-D-Phe or its stability. Our results are in contrast to
      ones reported previously, that DPP III variants bearing H(450)ELGH(455) exhibit
      activity. 

PMID- 24018668
TI  - Bioconversion of phosphatidylserine by phospholipase D from Streptomyces
      racemochromogenes in a microaqueous water-immiscible organic solvent.
AB  - Phospholipase D (PLD)-mediated transphosphatidylation of phosphatidylcholine (PC)
      in a biphasic system was limited by the hydrolysis reaction. A biphasic system
      can produce a large amount of water. To solve this problem, a microaqueous water
      immiscible organic solvent was used for the first time in the bioconversion of
      phosphatidylserine (PS). The transphosphatidylation among 40 umol PC, 800 umol L
      serine, and 0.17 U/mL PLD in 2.133 mL of butyl acetate with 6.25% water (V/V) was
      conducted at a trans-phosphatidylation rate of 88% (mol/mol), and no hydrolytic
      reaction was observed. Compared to commonly used biphasic systems, this system
      shows a similar transphosphatidylation rate, whereas the undesirable hydrolysis
      of phospholipids was completely suppressed. 

PMID- 24018669
TI  - Suppression of plasminogen activators and the MMP-2/-9 pathway by a Zanthoxylum
      avicennae extract to inhibit the HA22T human hepatocellular carcinoma cell
      migration and invasion effects in vitro and in vivo via phosphatase 2A
      activation.
AB  - This study shows that the ECM degradation-associated pathway, including uPA and
      tPA and the downstream MMP-2/-9 protein, was significantly suppressed in HA22T
      cells treated with a Zanthoxylum avicennae extract (YBBE). The endogenous
      inhibitors, including TIMP-1/-2 and PAI-1, were enhanced in HA22T cells by the
      YBBE treatment. The expression of MMP-2/-9 and TIMP-1/-2 was respectively
      assessed by using RT-PCR and a zymography assay. The mRNA levels and enzymatic
      activity of MMP-2/-9 were down-regulated by the YBBE treatment in a dose
      dependent manner, while the TIMP-1/-2 levels were conversely markedly increased.
      The PP2A siRNA or PP2A inhibitor totally reversed the YBBE effects, confirming
      the essential role of PP2A in YBBE inhibiting the HA22T cell migration and
      invasion effects. Xenografted animal experiments on nude mice demonstrated
      similiar results to the in vitro system. Both the in vitro and in vivo models
      clearly demonstrate that YBBE inhibited the highly metastatic HA22T liver cancer
      cell migration and invasion effects through PP2A activation. 

PMID- 24018670
TI  - Genomic features of Lactococcus lactis IO-1, a lactic acid bacterium that
      utilizes xylose and produces high levels of L-lactic acid.
AB  - Lactococcus lactis IO-1 (JCM7638) produces L-lactic acid predominantly when grown
      at high xylose concentrations, and its utilization is highly desired in the green
      plastics industry. Therefore it is worthwhile studying its genomic traits. In
      this study, we focused on (i) genes of possible horizontal transfer derivation
      (prophages, the nisin-sucrose transposon, and several restriction-modification
      systems), and (ii) genes for the synthetic pathways of amino acids and vitamins
      in the IO-1 genome. In view of the results of this analysis, we consider their
      meanings in strain IO-1. 

PMID- 24018671
TI  - Activation of immune responses in mice by an oral administration of bunching
      onion (Allium fistulosum) mucus.
AB  - Bunching onion [Allium fistulosum L. (Liliaceae)] secretes mucus in the cavities
      of its green leaves. The effects of the mucus, which is consumed as food, were
      examined. The mucus augmented the production of tumor necrosis factor (TNF)-alpha
      and monocyte chemotactic protein (MCP)-1 from RAW 264 cells and of interleukin
      (IL)-12 from J774.1 cells; however, extracts from green leaves and white sheaths
      did not. An oral administration of this mucus to mice augmented the immune
      functions of peritoneal cells by increasing TNF-alpha and IL-12 production and
      phagocytosis. It also augmented interferon (IFN)-gamma production from spleen
      cells and natural killer (NK) activity. These results suggest that an oral
      administration of the A. fistulosum mucus can enhance natural immunity. 

PMID- 24018672
TI  - Regulation of the basolateral Na+, K+-ATPase in the activation of electrogenic
      Na+ absorption induced by isoproterenol in the rat distal colon.
AB  - We investigated the effects of cAMP on the basolateral Na(+), K(+)-ATPase and
      apical amiloride-sensitive Na(+) channel in the rat distal colon. Under mucosal
      treatment with nystatin, isoproterenol and forskolin increased the basolateral
      Na(+) pump current. Under serosal treatment with ouabain, both agents slightly
      increased the amiloride-sensitive Na current, but not to a significant level. We
      concluded that cAMP activates the basolateral Na(+), K(+)-ATPase in the rat
      distal colon. 

PMID- 24018673
TI  - Identification of the glutaminase genes of Aspergillus sojae involved in
      glutamate production during soy sauce fermentation.
AB  - Glutaminase, an enzyme that catalyzes the conversion of L-glutamine to L
      glutamate, enhances the umami taste in soy sauce. The Aspergillus sojae genome
      contains 10 glutaminase genes. In this study, we estimated that approximately 60%
      of the glutamate in soy sauce is produced through the glutaminase reaction. To
      determine which glutaminase is involved in soy sauce glutamate production, we
      prepared soy sauces using single and multiple glutaminase gene disruptants of A.
      sojae. The glutamate concentration in soy sauce prepared using the DeltagahA
      DeltagahB-DeltaggtA-Deltagls disruptant was approximately 60% lower than that in
      the control strain, whereas it was decreased by approximately 20-30% in the
      DeltagahA-DeltagahB disruptant. However, the glutamate concentration was
      unchanged in the soy sauces prepared using the DeltagahA-DeltaggtA-Deltagls and
      DeltagahB-DeltaggtA-Deltagls disruptants. These results indicate that four
      glutaminases are involved in glutamate production in soy sauce, and that the
      peptidoglutaminase activities of GahA and GahB increase the glutamate
      concentration in soy sauce. 

PMID- 24018674
TI  - Identification and characterization of an inhibitor of trichothecene 3-O
      acetyltransferase, TRI101, by the chemical array approach.
AB  - Trichothecene 3-O-acetyltransferase (TRI101) is an indispensable enzyme for the
      biosynthesis of trichothecenes, a group of mycotoxins produced by Fusarium
      graminearum. In this study, an inhibitor of TRI101 was identified by chemical
      array analysis using compounds from the RIKEN Natural Products Depository
      (NPDepo) library. Although the addition of the identified enzyme inhibitor to the
      fungal culture did not inhibit trichothecene production, it can serve as a
      candidate lead compound in the development of a mycotoxin inhibitor that
      inactivates fungal defense mechanisms. 

PMID- 24018675
TI  - Sparassis crispa (Hanabiratake) ameliorates skin conditions in rats and humans.
AB  - Sparassis crispa (SC) is an edible mushroom with various medicinal properties. In
      this study, we investigated to determine whether SC would affect skin conditions
      in rats and humans. Oral administration of SC increased both turnover of the
      stratum corneum and dermal soluble collagen content in collagen synthetic
      activity-reduced model rats. To investigate the effects of oral intake of SC in
      humans, we performed a randomized, double-blind, placebo-controlled study. We
      found that cheek transepidermal water loss was significantly lower in the
      experimental group than in the control group at 4 weeks of ingestion. This study
      suggests that SC is effective and safe for the improvement of skin conditions. 

PMID- 24018676
TI  - Isolation and structural determination of makinolide B from Streptomyces sp. MK
      19.
AB  - A new 16-membered macrolide named makinolide B (1) was isolated from Streptomyces
      sp. MK-19. The structure of makinolide B (1) was determined on the basis of 2D
      NMR experiments involving DQF-COSY, TOCSY, HSQC, and HMBC methods. Application of
      the paper disk diffusion method to makinolide B (1) showed weak antibacterial
      activity against Staphylococcus aureus at the dose of 100 ug/disk. 

PMID- 24018677
TI  - Cell death caused by excision of centromeric DNA from a chromosome in
      Saccharomyces cerevisiae.
AB  - If genetically modified organisms (GMOs) are spread through the natural
      environment, it might affect the natural environment. To help prevent the spread
      of GMOs, we examined whether it is possible to introduce conditional lethality by
      excising centromeric DNA from a chromosome by site-specific recombination in
      Saccharomyces cerevisiae as model organism. First, we constructed haploid cells
      in which excision of the centromeric DNA from chromosome IV can occur due to
      recombinase induced by galactose. By this excision, cell death can occur. In
      diploid cells, cell death can also occur by excision from both homologous
      chromosomes IV. Furthermore, cell death can occur in the case of chromosome V. A
      small number of surviving cells appeared with excision of centromeric DNA, and
      the diploid showed greater viability than the haploid in both chromosomes IV and
      V. The surviving cells appeared mainly due to deletion of a recombination target
      site (RS) from the chromosome. 

PMID- 24018678
TI  - Influence of oxygen on alcoholic fermentation by a wine strain of Torulaspora
      delbrueckii: kinetics and carbon mass balance.
AB  - Torulaspora delbrueckii metabolism was assessed in a synthetic culture medium
      similar to grape must under various conditions: no aeration and three different
      oxygen feeds, in order to determine the effect of oxygen on metabolism. Carbon
      and nitrogen mass balances were calculated to quantify metabolic fluxes. The
      effect of oxygen was to decrease the flux of carbon going into the fermentation
      pathway in favor of growth. In the absence of aeration, higher amounts of
      glycerol were produced, probably to maintain the redox balance. The oxygen
      requirement of this strain was high, since even for the highest air supply oxygen
      became limiting after 24 h. Nevertheless, this strain developed well in the
      absence of oxygen and consumed 220 g/L of sugars (glucose/fructose) in 166 h at
      20  degrees C, giving a good ethanol yield (0.50 g/g). 

PMID- 24018679
TI  - Characterization of probiotic properties of Enterococcus faecium NHRD IHARA
      isolated from porcine feces.
AB  - We examined in vitro the adhesion of Enterococcus faecium NHRD IHARA (NHRD IHARA)
      to porcine small intestinal mucin (PSIM) and inhibition of the adherence of
      enteropathogenic bacteria due to pre-incubation of PSIM with NHRD IHARA. NHRD
      IHARA exhibited an effective barrier function in porcine small intestinal mucus
      layer. 

PMID- 24018680
TI  - Construction of an engineering strain producing high yields of alpha
      transglucosidase via Agrobacterium tumefaciens-mediated transformation of
      Asperillus niger.
AB  - In this study, Agrobacterium tumefaciens-mediated transformation (ATMT) was used
      in breeding industrial strains for the purpose of improving alpha
      transglucosidase production. Firstly, an efficient ATMT system for Asperillus
      niger was established by optimization of several influencing factors, in which
      transformation efficiency was improved up to 14-fold compared with the initial
      conditions. Furthermore, binary vector pBI-Glu containing an alpha
      transglucosidase expression cassette was constructed and transferred into
      Agrobacterium tumefaciens LBA4404 in order to infect A. niger. By the efficient
      ATMT method, the gene for alpha-transglucosidase, driven by strong promoter PglaA
      (the glucoamylase gene promoter), had a high expression level in A. niger A-8
      (25.02 U/mL). The optimized ATMT system was found to be effective and suitable
      for A. niger, and should be a useful tool for studying the function of A. niger
      genes and for industrial breeding of this strain. 

PMID- 24018681
TI  - Octaphlorethol A inhibits the CpG-induced inflammatory response by attenuating
      the mitogen-activated protein kinase and NF-kappaB pathways.
AB  - Octaphlorethol A is a phenolic compound isolated from the marine alga Ishige
      foliacea. In the present study, we investigated the anti-inflammatory activity of
      octaphlorethol A in CpG-stimulated primary murine bone marrow-derived macrophages
      and dendritic cells. It exhibited anti-inflammatory activity by regulating the
      mitogen-activated protein kinase and NF-kappaB pathways. 

PMID- 24018682
TI  - Purification and substrate specificity of a Ginkgo biloba glycosidase active in
      beta-1,2-xylosidic linkage in plant complex type N-glycans.
AB  - The beta-xylosidase, which is active against plant complex type N-glycans, was
      purified to homogeneity from Ginkgo biloba seeds. The N-terminal amino acid
      sequence, G-S-A-A-G-N-R-, of the Ginkgo beta-xylosidase (beta-Xyl'ase Gb) was
      consistent with the deduced internal amino acid sequence of an Arabidopsis beta
      xylosidase (AtBXL1). beta-Xyl'ase Gb hydrolyzed the beta1-2 xylosyl residue from
      Xylbeta1-2Manbeta1-4GlcNAcbeta1-4GlcNAc-PA and Xylbeta1-2Manbeta1-4GlcNAcbeta1
      4(Fucalpha1-3)GlcNAc-PA, but not that from Manalpha1-6(Manalpha1-3)(Xylbeta1
      2)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-3)GlcNAc-PA. 

PMID- 24018683
TI  - Effects of oral administration of glucosylceramide on gene expression changes in
      hairless mouse skin: comparison of whole skin, epidermis, and dermis.
AB  - The beneficial effects of dietary glucosylceramide on the barrier function of the
      skin have been increasingly reported, but the entire mechanism has not been
      clarified. By DNA microarray, we investigated changes in gene expression in
      hairless mouse skin when a damage-inducing AD diet and a glucosylceramide diet
      (GluCer) were imposed. GluCer administration potentially suppressed the
      upregulation of six genes and the downregulation of four genes in the AD group.
      Examination of the epidermal and/or dermal expression of Npr3, Cyp17a1, Col1a1,
      S100a9, Sprr2f, Apol7a, Tppp, and Scd3 revealed responses of various parts of the
      skin to the diets. In normal hairless mice, GluCer administration induced an
      increase in the dermal expression of Cyp17a1 and the epidermal expression of
      Tppp, and a decrease in the epidermal expression of S100a9. Our results provide
      information on gene expression not only in whole skin but also in the epidermis
      and dermis that should prove useful in the search for the mechanisms underlying
      the effects of GluCer on damaged and normal skin. 

PMID- 24018684
TI  - Characterization of constituents in the peel of Citrus kawachiensis
      (Kawachibankan).
AB  - Fifteen constituents, including a new compound, were isolated from an ethanolic
      extract of the peel of Citrus kawachiensis Hort. ex. Y. Tanaka (Japanese brand
      name, kawachibankan) which is one of the citrus products specific to Ehime,
      Japan. The new compound was characterized as 4'-dihydrophaseic acid beta
      glucopyranose ester (15) on the basis of spectral and chemical evidence. 

PMID- 24018685
TI  - Activation of the hTAS2R14 human bitter-taste receptor by (-)-epigallocatechin
      gallate and (-)-epicatechin gallate.
AB  - Tea catechins have strong bitterness and influence the taste of tea. Among the 25
      human bitter-taste receptors (TAS2Rs), we found that hTAS2R14 responded to
      catechins, in addition to hTAS2R39, a known catechin receptor. Although hTAS2R14
      responded to (-)-epicatechin gallate and (-)-epigallocatechin gallate, it did not
      respond to (-)-epicatechin and (-)-epigallocatechin. 

PMID- 24018686
TI  - Catalases CAT1 and CAT3 are not key enzymes in alleviating gamma irradiation
      induced DNA damage, H2O2 accumulation, or lipid peroxidation in Arabidopsis
      thaliana.
AB  - Gamma irradiation increased catalase activities at 0.1 kGy and decreased them at
      10 kGy in Arabidopsis wild type and catalase-deficient mutants, cat3-1 and cat1
      cat3. Irradiation induced DNA damage, H2O2 accumulation, and lipid peroxidation
      in both mutants as well as the wild type. Thus catalases might not be key enzymes
      protecting gamma irradiation-induced damage. 

PMID- 24018687
TI  - Low stability and a conserved N-glycosylation site are associated with regulation
      of the discoidin domain receptor family by glucose via post-translational N
      glycosylation.
AB  - Cell-surface expression of the discoidin domain receptor (DDR) tyrosine kinase
      family in high molecular mass form was controlled sensitively by the glucose
      concentration through a post-translational N-glycosylation process. Cycloheximide
      time-course experiments revealed that the high-molecular-mass forms of DDR1 and
      DDR2 were significantly less stable than control receptor tyrosine kinases. Site
      directed mutational analysis of the consensus N-glycosylation sites of the DDRs
      revealed that mutations of asparagine 213 of DDR2 and asparagine 211 of DDR1, a
      conserved N-glycosylation site among vertebrate DDRs, inhibited the generation of
      the high-molecular-mass isoform. Taken together, these results suggest a
      mechanism to control the activity of the DDR family by regulating its cell
      surface expression. Due to low stability, the steady-state population of
      functional DDR proteins in the cell surface depends sensitively on its maturation
      process via post-translational N-glycosylation, which is controlled by the
      glucose supply and the presence of a conserved N-glycosylation site. 

PMID- 24018688
TI  - Effects of food lectins on the transport system of human intestinal Caco-2 cell
      monolayers.
AB  - The effects of 16 lectins isolated from foodstuff on the transport system across
      human intestinal Caco-2 cell monolayers were investigated by using four
      fluorescent markers: lucifer yellow (LY) for the paracellular pathway,
      fluorescein (FL) for the monocarboxylic acid transporter-mediated pathway,
      rhodamine 123 for the P-glycoprotein-mediated efflux pathway, and calcein for the
      multidrug resistance associated protein-related efflux pathway. The
      transepithelial electrical resistance (TER) values for the monolayers were also
      measured. WGA from wheat germ, ABA from white mushroom, AOL from Aspergillus
      oryzae, and CSL3 from chum salmon eggs (each at 100 ug/mL) decreased the TER
      value by 20-40% which resulted in increased LY transport. These lectins, as well
      as such other lectins as SBA from soybean, RBA from rice bran, and Con A from
      jack bean, affected other transport pathways too. These results indicate that the
      lectins modulated the transepithelial transport system in different ways,
      probably because of their specific binding characteristics toward Caco-2 cell
      monolayers. 

PMID- 24018689
TI  - Identification and functional analysis of a Delta6-desaturase gene and the
      effects of temperature and wounding stresses on its expression in Microula
      sikkimensis leaves.
AB  - A Delta6-desaturase gene was isolated from Microula sikkimensis. Sequence
      analysis indicated that the gene, designated MsD6DES, had an open reading frame
      of 1,357 bp and encoded 448 amino acids. Heterologous expression in tobacco
      indicated that MsD6DES can use endogenous substrates to synthesize gamma
      linolenic acid (GLA, 18:3(Delta 6,9,12)) and octadecatetraenoic acid (OTA,
      18:4(Delta 6,9,12,15)). MsD6DES transcripts were distributed in all tested
      tissues, with high expression levels in seeds and young leaves. The effects of
      temperature and wounding stresses on MsD6DES expression were analyzed. The
      results indicated that temperature regulates MsD6DES at the transcriptional
      level. MsD6DES expression increased first, reaching a maximum 4 h after low
      temperature treatment. A slight increase in MsD6DES transcript levels was also
      observed under high temperature. We found that the response of MsD6DES to
      temperature stress was different from those of fungi and algae. In addition,
      MsD6DES was found to be wound-inducible. 

PMID- 24018690
TI  - Synthesis and bioassay of the eight analogues of the CH503 male pheromone (3
      acetoxy-11,19-octacosadien-1-ol) of the Drosophila melanogaster fruit fly.
AB  - Eight analogues of (3R,11Z,19Z)-CH503 (3-acetoxy-11,19-octacosadien-1-ol), the
      anti-aphrodisiac pheromone of male Drosophila melanogaster, were synthesized for
      a bioassay. These were the enantiomers of 3-acetoxy-11,19-octacosadiyn-1-ol (1),
      3-acetoxyoctacosan-1-ol (2), (Z)-3-acetoxy-11-octacosen-1-ol (3), and (Z)-3
      acetoxy-19-octacosen-1-ol (4). None of them were pheromonally active, indicating
      that the two double bonds at C-11 and C-19 were necessary for bioactivity. 

PMID- 24018691
TI  - Functional expression of Schizosaccharomyces pombe Vba2p in the vacuolar membrane
      of Saccharomyces cerevisiae.
AB  - A vacuolar membrane protein, Vba2p of Schizosaccharomyces pombe, is involved in
      basic amino acid uptake by intact cells. Here we found evidence that Vba2p
      mediated ATP-dependent lysine uptake by vacuolar membrane vesicles of
      Saccharomyces cerevisiae. Vba2p was also responsible for quinidine sensitivity,
      and the addition of lysine improved cell growth on quinidine-containing media.
      These findings should be useful for further characterization of Vba2p. 

PMID- 24018692
TI  - Phytohormones in Japanese mugwort gall induction by a gall-inducing gall midge.
AB  - A variety of insect species induce galls on host plants. Liquid
      chromatographic/tandem mass spectrometric analyses showed that a gall midge
      (Rhopalomyia yomogicola) that induces galls on Artemisia princeps contained high
      levels of indole-3-acetic acid and cytokinins. The gall midge larvae also
      synthesized indole-3-acetic acid from tryptophan. Close observation of gall
      tissue sections indicated that the larval chamber was surrounded by layers of
      cells having secondary cell walls with extensive lignin deposition, except for
      the part of the gall that constituted the feeding nutritive tissue which was
      composed of small cells negatively stained for lignin. The differences between
      these two types of tissue were confirmed by an expression analysis of the genes
      involved in the synthesis of the secondary cell wall. Phytohormones may have
      functioned in maintaining the feeding part of the gall as fresh nutritive tissue.
      Together with the results in our previous study, those presented here suggest the
      importance of phytohormones in gall induction. 

PMID- 24018693
TI  - Purification and characterization of 1,3-beta-D-glucan phosphorylase from
      Ochromonas danica.
AB  - 1,3-beta-D-glucan phosphorylase (BGP) is an enzyme that catalyzes the reversible
      phosphorolysis of 1,3-beta-glucosidic linkages to form alpha-D-glucose 1
      phosphate (G1P). Here we report on the purification and characterization of BGP
      from Ochromonas danica (OdBGP). The purified enzyme preparation showed three
      bands (113, 118, and 124 kDa) on SDS-polyacrylamide gel electrophoresis. The
      optimum pH and temperature were 5.5 and 25  degrees C-30  degrees C. OdBGP
      phosphorolysed laminaritriose, larger laminarioligosaccharides, and laminarin,
      but not laminaribiose. In the synthesis reaction, laminarin and
      laminarioligosaccharides served as good acceptors, but OdBGP did not act on
      glucose. Kinetic analysis indicated that the phosphorolysis reaction of OdBGP
      follows a sequential Bi Bi mechanism. The equilibrium of the enzymatic reaction
      indicated that OdBGP favors the reaction in the synthetic direction. Overnight
      incubation of OdBGP with laminaribiose and G1P resulted in the formation of
      precipitates, which were probably 1,3-beta-glucans.

PMID- 24018694
TI  - Intraspinal stem cell transplantation in amyotrophic lateral sclerosis: a phase I
      trial, cervical microinjection, and final surgical safety outcomes.
AB  - BACKGROUND: The first US Food and Drug Administration approved clinical trial for
      a stem cell-based treatment of amyotrophic lateral sclerosis has now been
      completed. OBJECTIVE: Primary aims assessed the safety of a direct microinjection
      based technique and the toxicity of neural stem cell transplantation to the
      ventral horn of the cervical and thoracolumbar spinal cord. Results from
      thoracolumbar-only microinjection groups have been previously published. Cervical
      and cervical plus thoracolumbar microinjection group perioperative morbidity
      results are presented. METHODS: Eighteen microinjection procedures (n = 12
      thoracolumbar [T10/11], n = 6 cervical [C3-5]) delivered NSI-566RSC (Neuralstem,
      Inc), a human neural stem cell, to 15 patients in 5 cohorts. Each injection
      series comprised 5 injections of 10 MUL at 4-mm intervals. The patients in group
      A (n = 6) were nonambulatory and received unilateral (n = 3) or bilateral (n = 3)
      thoracolumbar microinjections. The patients in groups B to E were ambulatory and
      received either unilateral (group B, n = 3) or bilateral (group C, n = 3)
      thoracolumbar microinjection. Group D and E patients received unilateral cervical
      (group D, n = 3) or cervical plus bilateral thoracolumbar microinjection (group
      E, n = 3). RESULTS: Unilateral cervical (group D, n = 3) and cervical plus
      thoracolumbar (group E, n = 3) microinjections to the ventral horn have been
      completed in ambulatory patients. One patient developed a postoperative kyphotic
      deformity prompting completion of a laminoplasty in subsequent patients. Another
      required reoperation for wound dehiscence and infection. The solitary patient
      with bulbar amyotrophic lateral sclerosis required perioperative reintubation.
      CONCLUSION: Delivery of a cellular payload to the cervical or thoracolumbar
      spinal cord was well tolerated by the spinal cord in this vulnerable population.
      This encouraging finding supports consideration of this delivery approach for
      neurodegenerative, oncologic, and traumatic spinal cord afflictions.

PMID- 24018695
TI  - The relationship of aphasia type and gesture production in people with aphasia.
AB  - PURPOSE: For many individuals with aphasia, gestures form a vital component of
      message transfer and are the target of speech-language pathology intervention.
      What remains unclear are the participant variables that predict successful
      outcomes from gesture treatments. The authors examined the gesture production of
      a large number of individuals with aphasia-in a consistent discourse sampling
      condition and with a detailed gesture coding system-to determine patterns of
      gesture production associated with specific types of aphasia. METHOD: The authors
      analyzed story retell samples from AphasiaBank (TalkBank, n.d.), gathered from 98
      individuals with aphasia resulting from stroke and 64 typical controls. Twelve
      gesture types were coded. Descriptive statistics were used to describe the
      patterns of gesture production. Possible significant differences in production
      patterns according to aphasia type were examined using a series of chi-square,
      Fisher exact, and logistic regression statistics. RESULTS: A significantly higher
      proportion of individuals with aphasia gestured as compared to typical controls,
      and for many individuals with aphasia, this gesture was iconic and was capable of
      communicative load. Aphasia type impacted significantly on gesture type in
      specific identified patterns, detailed here. CONCLUSION: These type-specific
      patterns suggest the opportunity for gestures as targets of aphasia therapy.

PMID- 24018696
TI  - Use of the Children's Communication Checklist-2 for classification of language
      impairment risk in young school-age children with attention-deficit/hyperactivity
      disorder.
AB  - PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) are at
      elevated risk for language impairment (LI). This study examined the feasibility
      of using the Children's Communication Checklist-2 (CCC-2; Bishop, 2006) to
      classify risk for LI in young children, ages 5-8 years, with ADHD. METHOD:
      Parents of 32 children with ADHD and 12 typically developing peers completed the
      CCC-2. The Clinical Evaluation of Language Fundamentals, Fourth Edition (Semel,
      Wiig, & Secord, 2003) and the Test of Narrative Language (Gillam & Pearson, 2004)
      were administered to diagnose LI. Language samples were collected to examine
      clinical markers of LI. RESULTS: CCC-2 General Communication Composite scores <=
      85 correctly classified 10 participants with ADHD diagnosed with LI as defined by
      composite scores <= 85 on the Clinical Evaluation of Language Fundamentals,
      Fourth Edition, or on the Test of Narrative Language. Five of these participants
      demonstrated 1 or more clinical markers of LI in language samples. Three
      additional participants, who received a General Communication Composite score <=
      85 yet scored above 85 on the language tests, demonstrated CCC-2 profiles
      suggestive of pragmatic impairment. Sensitivity and specificity rates were 100%
      and 85.29%, respectively. CCC-2 scores and most measures were significantly
      correlated. CONCLUSION: The results support the feasibility of using the CCC-2 as
      a screener to identify children with ADHD who are at elevated risk for LI and
      need referral for comprehensive assessment.

PMID- 24018697
TI  - Children's responses to telegraphic and grammatically complete prompts to
      imitate.
AB  - PURPOSE: The purpose of this study was to determine whether children in the early
      stage of combining words are more likely to respond to imitation prompts that are
      telegraphic than to prompts that are grammatically complete and whether they
      produce obligatory grammatical morphemes more reliably in response to
      grammatically complete imitation prompts than to telegraphic prompts. METHOD:
      Five children between 30 and 51 months of age with language delay participated in
      a single-case alternating treatment design with 14 sessions split between a
      grammatical and a telegraphic condition. Alternating orders of the 14 sessions
      were randomly assigned to each child. Children were given 15 prompts to imitate a
      semantic relation that was either grammatically complete or telegraphic. RESULTS:
      No differences between conditions were found for the number of responses that
      contained a semantic relation. In contrast, 3 of the 5 children produced
      significantly more grammatical morphemes when presented with grammatically
      complete imitation prompts. Two children did not include a function word in
      either condition. CONCLUSION: Providing a telegraphic prompt to imitate does not
      offer any advantage as an intervention technique. Children are just as likely to
      respond to a grammatically complete imitation prompt. Further, including function
      words encourages children who are developmentally ready to imitate them.

PMID- 24018698
TI  - An enhanced protocol for constraint-induced aphasia therapy II: a case series.
AB  - PURPOSE: The initial version of Constraint-Induced Aphasia Therapy (CIAT I)
      consisted of a single exercise. This study sought to evaluate the feasibility for
      future trials of an expanded and restructured protocol designed to increase the
      efficacy of CIAT I. METHOD: The subjects were 4 native English speakers with
      chronic stroke who exhibited characteristics of moderate Broca's aphasia.
      Treatment was carried out for 3.5 hr/day for 15 consecutive weekdays. It
      consisted of 3 components: (a) intensive training by a behavioral method termed
      shaping using a number of expressive language exercises in addition to the single
      original language card game, (b) strong discouragement of attempts to use gesture
      or other nonverbal means of communication, and (c) a transfer package of
      behavioral techniques to promote transfer of treatment gains from the laboratory
      to real-life situations. RESULTS: Participation in speech in the life situation
      improved significantly after treatment. The effect sizes (i.e., d') in this
      domain were >= 2.2; d' values >= 0.8 are considered large. Improvement in
      language ability on a laboratory test, the Western Aphasia Battery-Revised
      (Kertesz, 2006), did not achieve statistical significance, although the effect
      size was large--that is, 1.3 (13.1 points). CONCLUSION: These pilot results
      suggest in preliminary fashion that CIAT II may produce significant improvements
      in everyday speech.

PMID- 24018701
TI  - Non-urgent encounters in a Swiss medical emergency unit.
AB  - BACKGROUND: Emergency department crowding is a growing international problem. One
      possible reason for crowding might be the rising number of "walk-in" patients
      presenting with "non-urgent" health complaints. METHODS: In a retrospective
      cohort study in adult medical patients presenting to the emergency unit of the
      University Hospital Zurich, we determined the frequency of "non-urgent"
      encounters, examined patient characteristics predictive for such encounters, and
      explored the impact of a simple, non-validated triage tool on diverting "non
      urgent" cases to alternate sites of primary care. RESULTS: We included 1,175 and
      1,448 medical encounters before (1-31 January 2008) and after (1-31 January 2009)
      the implementation of the triage tool. Almost one out of three patients presented
      with a minor "non-urgent" health complaint (29.9% [95%CI 28.1%-31.6%]). The most
      common were "cough/sneezing" (7.82% [95%CI 6.79%-8.84%]), "follow-up" (6.44%
      [95%CI 5.50%-7.38%]), and "weakness/tiredness" (3.47% [95%CI 2.77%-4.17%]).
      Significant predictors for "non-urgent" encounters were young age (mean adjusted
      odds ratio 0.93 [95%CI 0.88-0.97] for each additional decade of life), and non
      Swiss origin (adjusted odds ratio 1.18 [95%CI 1.02-1.31]). The triage tool did
      not divert "non-urgent" cases from the emergency unit to outpatient care
      (adjusted odds ratio 0.94 [95%CI 0.80-1.12]). CONCLUSION: In the emergency unit
      of the University Hospital Zurich, the prevalence of "non-urgent" medical
      encounters was substantial with one out three patients presenting with minor
      health complaints. Young age and non-Swiss origin were associated with increased
      use of the emergency unit for "non-urgent" conditions. A simple triage tool did
      not effectively divert "non-urgent" cases to alternates sites of primary care.

PMID- 24018702
TI  - Diversity of Planctomycetes in iron-hydroxide deposits from the Arctic Mid Ocean
      Ridge (AMOR) and description of Bythopirellula goksoyri gen. nov., sp. nov., a
      novel Planctomycete from deep sea iron-hydroxide deposits.
AB  - Planctomycetes form a deep branching and distinct phylum of the domain Bacteria,
      and represent a fascinating group due to their unusual features such as
      intracellular compartmentalization and lack of peptidoglycan in their cell walls.
      The phylum Planctomycetes was described already in 1924, but still the diversity
      of this phylum represents an enigma and unexploited resource. In this study the
      diversity of the phylum Planctomycetes in low temperature iron-hydroxide deposits
      at the Mohns Ridge, a part of the Arctic Mid Ocean Ridge (AMOR), was
      characterised by descriptive analysis of 16S rRNA gene sequences in combination
      with isolation of planctomycetes strains. The 16S rRNA gene sequences were
      affiliated with three order within the phylum Planctomycetes namely the
      (i)Planctomycetales, (ii) "Candidatus Brocadiales" and (iii) Phycisphaerae in
      addition to sequences affiliating to hitherto unknown Planctomycetes. The
      majority of the sequences were affiliated with the CCM11a group (Phycisphaerae),
      and with the Pir4 group (Planctomycetaceae). Two strains from the order
      Planctomycetales were isolated. One strain (Plm2) showed high similarity to the
      previously isolated Planctomyces maris (99 % 16S rRNA sequence identity). The
      other strain (Pr1d) belonged to the Pir4 group, and showed highest identity with
      Rhodopirellula baltica (86 %), Blastopirellula marina (86 %) and Pirellula
      staleyi (85 %). Based on its physiological and biochemical properties, strain
      Pr1d(T) is considered to represent a new genus of the order Planctomycetales. We
      propose to classify the novel planctomycete in a new genus and species,
      Bythoypirellula goksoyri gen. nov., sp. nov., the type strain being Pr1d(T).

PMID- 24018703
TI  - Interface-engineered bistable [2]rotaxane-graphene hybrids with logic
      capabilities.
AB  - The use of high-quality graphene as a local probe in combination with photo
      excitation helps to establish a deep mechanistic understanding of charge
      generation/quenching processes under lying the graphene/environment interface. By
      combining a non-destructive bottom-up assembly technique with sensitive graphene
      based transistors, a bistable [2]rotaxane-graphene hybrid device, which exhibits
      a symmetric mirror-image photoswitching effect with logic capabilities, is
      produced. 

PMID- 24018704
TI  - Physiotherapy versus placebo or no intervention in Parkinson's disease.
AB  - BACKGROUND: Despite medical therapies and surgical interventions for Parkinson's
      disease (PD), patients develop progressive disability. Physiotherapy aims to
      maximise functional ability and minimise secondary complications through movement
      rehabilitation within a context of education and support for the whole person.
      The overall aim is to optimise independence, safety, and well-being, thereby
      enhancing quality of life. OBJECTIVES: To assess the effectiveness of
      physiotherapy intervention compared with no intervention in patients with PD.
      SEARCH METHODS: We identified relevant trials by conducting electronic searches
      of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, and
      by handsearching major journals, abstract books, conference proceedings, and
      reference lists of retrieved publications. The literature search included trials
      published up to the end of January 2012. SELECTION CRITERIA: Randomised
      controlled trials of physiotherapy intervention versus no physiotherapy
      intervention in patients with PD. DATA COLLECTION AND ANALYSIS: Two review
      authors independently extracted data from each article. We used standard meta
      analysis methods to assess the effectiveness of physiotherapy intervention
      compared with no physiotherapy intervention. Trials were classified into the
      following intervention comparisons: general physiotherapy, exercise, treadmill
      training, cueing, dance, and martial arts. We used tests for heterogeneity to
      assess for differences in treatment effect across these different physiotherapy
      interventions. MAIN RESULTS: We identified 39 trials with 1827 participants. We
      considered the trials to be at a mixed risk of bias as the result of unreported
      allocation concealment and probable detection bias. Compared with no
      intervention, physiotherapy significantly improved the gait outcomes of speed
      (mean difference 0.04 m/s, 95% confidence interval (CI) 0.02 to 0.06, P =
      0.0002); two- or six-minute walk test (13.37 m, 95% CI 0.55 to 26.20, P = 0.04)
      and Freezing of Gait questionnaire (-1.41, 95% CI -2.63 to -0.19, P = 0.02);
      functional mobility and balance outcomes of Timed Up & Go test (-0.63 s, 95% CI 
      1.05 to -0.21, P = 0.003), Functional Reach Test (2.16 cm, 95% CI 0.89 to 3.43, P
      = 0.0008), and Berg Balance Scale (3.71 points, 95% CI 2.30 to 5.11, P <
      0.00001); and clinician-rated disability using the Unified Parkinson's Disease
      Rating Scale (UPDRS) (total -6.15 points, 95% CI-8.57 to -3.73, P < 0.00001;
      activities of daily living: -1.36, 95% CI -2.41 to -0.30, P = 0.01; and motor: 
      5.01, 95% CI -6.30 to -3.72, P < 0.00001). No difference between arms was noted
      in falls (Falls Efficacy Scale: -1.91 points, 95% CI -4.76 to 0.94, P = 0.19) or
      patient-rated quality of life (PDQ-39 Summary Index: -0.38 points, 95% CI -2.58
      to 1.81, P = 0.73). One study reported that adverse events were rare; no other
      studies reported data on this outcome. Indirect comparisons of the different
      physiotherapy interventions revealed no evidence that the treatment effect
      differed across physiotherapy interventions for any of the outcomes assessed.
      AUTHORS' CONCLUSIONS: Benefit for physiotherapy was found in most outcomes over
      the short term (i.e. < 3 months) but was significant only for speed, two- or six
      minute walk test, Freezing of Gait questionnaire, Timed Up & Go, Functional Reach
      Test, Berg Balance Scale, and clinician-rated UPDRS. Most of the observed
      differences between treatments were small. However, for some outcomes (e.g.
      speed, Berg Balance Scale, UPDRS), the differences observed were at, or
      approaching, what are considered minimal clinically important changes. These
      benefits should be interpreted with caution because the quality of most of the
      included trials was not high. Variation in measurements of outcome between
      studies meant that our analyses include a small proportion of the participants
      recruited.This review illustrates that a wide range of approaches are employed by
      physiotherapists to treat patients with PD. However, no evidence of differences
      in treatment effect was noted between the different types of physiotherapy
      interventions being used, although this was based on indirect comparisons. A
      consensus menu of 'best practice' physiotherapy is needed, as are large, well
      designed randomised controlled trials undertaken to demonstrate the longer-term
      efficacy and cost-effectiveness of 'best practice' physiotherapy in PD.

PMID- 24018706
TI  - 2013 Lasker Awards honor biomedical researchers and champions of public service.

PMID- 24018705
TI  - Influence of diblock copolymer PCL-mPEG and of various iodinated oils on the
      formulation by the emulsion-solvent diffusion process of radiopaque polymeric
      nanoparticles.
AB  - This pioneer study in the domain of blood pool contrast media formulation
      presents the influence of poly-E-caprolactone-monomethoxy poly(ethylene glycol)
      (PCL-mPEG) and oils on the formulation of polymeric nanoparticles by emulsion
      solvent diffusion. The nature of the oil used had no influence on the
      encapsulation rate, even if particles were formulated with a mix of PCL/PCL-mPEG.
      It did, however, influence the particle size and polydispersity, with
      macroglycerides appearing to be the lipid structure best suited to obtain the
      smallest monodisperse particles. When we used PCL-mPEG to form a PEG-hydrated
      layer to surround the nanoparticles, its tension active property had a favorable
      effect on particle size and polydispersity. We also showed the strong deleterious
      effect on particle size and polydispersity when the polymer proportion was
      increased to over 1% (w/v) in the pre-emulsion organic phase. Conversely,
      increasing the oil proportion in this organic phase simply resulted in a slight
      to insignificant deleterious effect on size and polydispersity, enabling the oil
      proportion to be enhanced up to 3% (w/v). Finally, we showed the favorable
      combined effect of oil iodination and the presence of PCL-mPEG on particles
      formulated by emulsion-solvent diffusion leading to the preparation of smaller
      polymeric iodine-containing particles.

PMID- 24018707
TI  - Molecular characterization and phylogeny of whipworm nematodes inferred from DNA
      sequences of cox1 mtDNA and 18S rDNA.
AB  - A molecular phylogenetic hypothesis is presented for the genus Trichuris based on
      sequence data from the mitochondrial cytochrome c oxidase 1 (cox1) and ribosomal
      18S genes. The taxa consisted of different described species and several host
      associated isolates (undescribed taxa) of Trichuris collected from hosts from
      Spain. Sequence data from mitochondrial cox1 (partial gene) and nuclear 18S near
      complete gene were analyzed by maximum likelihood and Bayesian inference methods,
      as separate and combined datasets, to evaluate phylogenetic relationships among
      taxa. Phylogenetic results based on 18S ribosomal DNA (rDNA) were robust for
      relationships among species; cox1 sequences delimited species and revealed
      phylogeographic variation, but most relationships among Trichuris species were
      poorly resolved by mitochondrial sequences. The phylogenetic hypotheses for both
      genes strongly supported monophyly of Trichuris, and distinct genetic lineages
      corresponding to described species or nematodes associated with certain hosts
      were recognized based on cox1 sequences. Phylogenetic reconstructions based on
      concatenated sequences of the two loci, cox1 (mitochondrial DNA (mtDNA)) and 18S
      rDNA, were congruent with the overall topology inferred from 18S and previously
      published results based on internal transcribed spacer sequences. Our results
      demonstrate that the 18S rDNA and cox1 mtDNA genes provide resolution at
      different levels, but together resolve relationships among geographic populations
      and species in the genus Trichuris. 

PMID- 24018708
TI  - An EF-handed Ca(2+)-binding protein of Chinese liver fluke Clonorchis sinensis.
AB  - A cDNA clone encoding 8 kDa protein was retrieved from an EST pool of Chinese
      liver fluke Clonorchis sinensis. A deduced polypeptide of the cDNA clone was
      similar to 8 kDa Ca(2+)-binding proteins from other parasitic trematodes, and,
      thus, named as CsCa8, containing two EF-hand Ca(2+)-binding sites. Homology
      models predicted CsCa8 to be a single globular structure having four helices and
      molecular folds similar to Ca(2+)-binding state of other small Ca(2+)-binding
      proteins. Recombinant CsCa8 protein showed specific Ca(2+)-binding affinity and
      shifting in native gel mobility assay. Mouse immune sera raised against
      recombinant CsCa8 protein recognized native CsCa8 from adult C. sinensis worm
      extract. CsCa8 was localized in oral and ventral suckers, vitelline follicles and
      subtegumental tissues. These findings suggest that CsCa8 might be involved in
      cellular Ca(2+) signal transduction for muscle contraction and egg production. 

PMID- 24018709
TI  - Characterization of Trypanosoma cruzi infectivity, proliferation, and cytokine
      patterns in gut and pancreatic epithelial cells maintained in vitro.
AB  - Trypanosoma cruzi infects all nucleated cells in both humans and experimental
      animals. As a prelude to our studies of T. cruzi pathogenesis in the
      gastrointestinal system, we have initiated in vitro cultures of gut (Caco-2 and
      HT-29) and pancreatic (Panc-1) epithelial cells. We show that along with primary
      human fibroblasts, all three cell lines are susceptible to infection and support
      proliferation of T. cruzi. Infection with T. cruzi modified dramatically the
      cytokines elaborated by these cells. Substantially greater quantities of IL-5 and
      TGF-beta1 were produced by fibroblasts and Caco-2 and Panc-1 cells, whereas
      secretion of IFN-gamma and TNF-alpha was greatly reduced in all three cell types.
      Since these cells are not known to be the primary sources of IFN-gamma, we
      examined IFN-gamma mRNA expression in these cells. Both Caco-2 and Panc-1 cells
      were found to express IFN-gamma mRNA, validating its secretion. These findings
      may provide insight into signaling pathways that mediate innate immunity to T.
      cruzi and pathogenesis of gastrointestinal and pancreatic alterations in Chagas
      disease. 

PMID- 24018710
TI  - High level of dioxin-TEQ in tissue is associated with Agent Orange exposure but
      not with biochemical recurrence after radical prostatectomy.
AB  - BACKGROUND: Agent Orange (AO) was previously identified as a significant risk
      factor for biochemical recurrence (BCR) after radical prostatectomy (RP) in
      prostate cancer patients. In this study, we determined the levels of dioxin
      biological toxicity using toxic equivalency (TEQ) values and examined the impact
      of dioxin-TEQ level on BCR. METHODS: A total of 93 men who underwent RP, with a
      median of 5.3 years of postoperative follow-up, were included in the study. The
      dioxin-TEQ level of each patient was measured using intraoperatively harvested
      abdominal subcutaneous fat. The dichotomous categorization of dioxin-TEQ by the
      50th percentile (low<50% vs high? 50%) was also used to regroup the patient
      cohort, regardless of the previous history of AO exposure. Comparisons between
      the dioxin-TEQ levels, clinicopathological characteristics and BCR in AO-exposed
      and -unexposed men were made to allocate possible risk factors. The multivariable
      logistic regression model was used to identify significant risk factors
      associated with BCR, adjusting for other confounding factors. RESULTS: The median
      dioxin-TEQ level in 37 AO-exposed patients was significantly higher than that in
      56 unexposed patients (22.3 vs 15.0 pg g(-1) fat, respectively, P<0.001). The men
      with AO exposure were more likely to have a high dioxin-TEQ level (P<0.001).
      Neither AO exposure nor the level of dioxin-TEQ was associated with BCR. Tumor
      stage (T3/T4 vs T2) and Gleason grade (Gleason ?3+4) were independent risk
      factors for BCR after RP. CONCLUSIONS: Exposure to AO significantly increases the
      adipose level of dioxin-TEQ in patients treated with RP. However, exposure to AO
      or a high dioxin-TEQ level was not associated with an increased risk of BCR after
      RP. This lack of association supports the current conclusion that the evidence of
      carcinogenicity of AO in prostate cancer patients is not sufficient and remains
      'limited'.

PMID- 24018711
TI  - Role of combined use of ketoconazole and tamsulosin in management of acute
      urinary retention due to benign prostatic obstruction (a randomized controlled
      trial).
AB  - BACKGROUND: Ketoconazole has the ability to lower serum testosterone to castrate
      level within 48 h. As the prostate is an androgen-dependent organ, we
      investigated the effect of the use of tamsulosin in combination with ketoconazole
      in cases of acute urinary retention (AUR) due to benign prostatic obstruction
      (BPO). METHODS: We recruited patients with AUR secondary to BPO but those with
      hepatic or renal impairment were excluded. Following urethral catheterization,
      the participants were randomized into two equal groups. The first group received
      tamsulosin (0.4 mg o.d.) and ketoconazole (200 mg t.d.s.) while the second one
      had tamsulosin and placebo. The drugs were maintained for 7 days and then the
      patients were put on trial without catheter (TWOC). The successful cases were
      assessed with peak flow rate (PFR) and the post-void residual urine volume (PVRV)
      was also estimated. RESULTS: We included 106 men with a mean age of 64.1+/-5.2
      years and a mean prostate size of 61.6+/-14.6 g in the two groups. The received
      medications were well tolerated by all patients and none of them had discontinued
      the prescribed drugs. The incidence of the successful TWOC was significantly
      higher in the combined treatment group (77.35%) compared to the tamsulosin group
      (58.84%; P=0.01). Among those who had a successful TWOC, the PFR and the PVRV
      were also significantly better in the combined treatment group compared to the
      other one (P=0.001). CONCLUSIONS: Patients with AUR due to BPO can be treated
      safely with a combination of ketoconazole and tamsulosin to get a better success
      rate of TWOC.

PMID- 24018712
TI  - The frequency and cost of treatment perceived to be futile in critical care.
AB  - IMPORTANCE: Physicians often perceive as futile intensive care interventions that
      prolong life without achieving an effect that the patient can appreciate as a
      benefit. The prevalence and cost of critical care perceived to be futile have not
      been prospectively quantified. OBJECTIVE: To quantify the prevalence and cost of
      treatment perceived to be futile in adult critical care. DESIGN, SETTING, AND
      PARTICIPANTS: To develop a common definition of futile care, we convened a focus
      group of clinicians who care for critically ill patients. On a daily basis for 3
      months, we surveyed critical care specialists in 5 intensive care units (ICUs) at
      an academic health care system to identify patients whom the physicians believed
      were receiving futile treatment. Using a multivariate model, we identified
      patient and clinician characteristics associated with patients perceived to be
      receiving futile treatment. We estimated the total cost of futile treatment by
      summing the charges of each day of receiving perceived futile treatment and
      converting to costs. MAIN OUTCOME AND MEASURE: Prevalence of patients perceived
      to be receiving futile treatment. RESULTS: During a 3-month period, there were
      6916 assessments by 36 critical care specialists of 1136 patients. Of these
      patients, 904 (80%) were never perceived to be receiving futile treatment, 98
      (8.6%) were perceived as receiving probably futile treatment, 123 (11%) were
      perceived as receiving futile treatment, and 11 (1%) were perceived as receiving
      futile treatment only on the day they transitioned to palliative care. The
      patients with futile treatment assessments received 464 days of treatment
      perceived to be futile in critical care (range, 1-58 days), accounting for 6.7%
      of all assessed patient days in the 5 ICUs studied. Eighty-four of the 123
      patients perceived as receiving futile treatment died before hospital discharge
      and 20 within 6 months of ICU care (6-month mortality rate of 85%), with
      survivors remaining in severely compromised health states. The cost of futile
      treatment in critical care was estimated at $2.6 million. CONCLUSIONS AND
      RELEVANCE: In 1 health system, treatment in critical care that is perceived to be
      futile is common and the cost is substantial.

PMID- 24018713
TI  - An efficient synthesis of polysubstituted pyrroles via copper-catalyzed coupling
      of oxime acetates with dialkyl acetylenedicarboxylates under aerobic conditions.
AB  - A Cu-catalyzed [3+2]-type condensation reaction of oxime acetates and dialkyl
      acetylenedicarboxylates that provides highly substituted pyrroles under aerobic
      conditions is described. The newly formed pyrroles are easily employed for
      further transformations to prepare pyrrolo[2,1-a]isoquinoline skeletons. 

PMID- 24018714
TI  - Respiration impacts phase difference-based field maps in echo planar imaging.
AB  - PURPOSE: To investigate the influence of respiration on field maps for geometric
      distortion correction derived from two rapidly acquired consecutive echo planar
      images. METHODS: Displacement maps of the brains of seven healthy volunteers were
      acquired under breath hold and free breathing for a 64 * 64 pixel image matrix
      using phase labeling for additional coordinate encoding (PLACE). The maps were
      transformed into undistorted gradient echo space and analyzed with regard to
      standard deviation and absolute deviation from an accurate reference field map
      derived from a multiecho reference scan. RESULTS: Standard deviations between
      PLACE field maps and absolute difference from the reference field map are a
      factor of about 3 higher under free breathing than under breath hold. The mean
      deviation decreases from 3 pixels in the slice closest to the lung to 1 pixel in
      the most superior slice under free breathing and from 1 to <0.5 pixels under
      breath hold. CONCLUSION: Maps obtained under free breathing can significantly
      impact the field map and thus corrupt the geometric distortion correction. The
      effect can be greatly reduced by acquiring the field map data under breath hold.
      Data acquired under free breathing can be improved with retrospective phase
      correction or by averaging several field maps.

PMID- 24018715
TI  - Attentional selection in visual perception, memory and action: a quest for cross
      domain integration.
AB  - For decades, the cognitive and neural sciences have benefitted greatly from a
      separation of mind and brain into distinct functional domains. The tremendous
      success of this approach notwithstanding, it is self-evident that such a view is
      incomplete. Goal-directed behaviour of an organism requires the joint functioning
      of perception, memory and sensorimotor control. A prime candidate for achieving
      integration across these functional domains are attentional processes.
      Consequently, this Theme Issue brings together studies of attentional selection
      from many fields, both experimental and theoretical, that are united in their
      quest to find overreaching integrative principles of attention between
      perception, memory and action. In all domains, attention is understood as
      combination of competition and priority control ('bias'), with the task as a
      decisive driving factor to ensure coherent goal-directed behaviour and cognition.
      Using vision as the predominant model system for attentional selection, many
      studies of this Theme Issue focus special emphasis on eye movements as a
      selection process that is both a fundamental action and serves a key function in
      perception. The Theme Issue spans a wide range of methods, from measuring human
      behaviour in the real word to recordings of single neurons in the non-human
      primate brain. We firmly believe that combining such a breadth in approaches is
      necessary not only for attentional selection, but also to take the next decisive
      step in all of the cognitive and neural sciences: to understand cognition and
      behaviour beyond isolated domains. 

PMID- 24018716
TI  - Temporal expectancy in the context of a theory of visual attention.
AB  - Temporal expectation is expectation with respect to the timing of an event such
      as the appearance of a certain stimulus. In this paper, temporal expectancy is
      investigated in the context of the theory of visual attention (TVA), and we begin
      by summarizing the foundations of this theoretical framework. Next, we present a
      parametric experiment exploring the effects of temporal expectation on perceptual
      processing speed in cued single-stimulus letter recognition with unspeeded motor
      responses. The length of the cue-stimulus foreperiod was exponentially
      distributed with one of six hazard rates varying between blocks. We hypothesized
      that this manipulation would result in a distinct temporal expectation in each
      hazard rate condition. Stimulus exposures were varied such that both the temporal
      threshold of conscious perception (t0 ms) and the perceptual processing speed (v
      letters s(-1)) could be estimated using TVA. We found that the temporal threshold
      t0 was unaffected by temporal expectation, but the perceptual processing speed v
      was a strikingly linear function of the logarithm of the hazard rate of the
      stimulus presentation. We argue that the effects on the v values were generated
      by changes in perceptual biases, suggesting that our perceptual biases are
      directly related to our temporal expectations. 

PMID- 24018717
TI  - Feature-based attention: it is all bottom-up priming.
AB  - Feature-based attention (FBA) enhances the representation of image
      characteristics throughout the visual field, a mechanism that is particularly
      useful when searching for a specific stimulus feature. Even though most theories
      of visual search implicitly or explicitly assume that FBA is under top-down
      control, we argue that the role of top-down processing in FBA may be limited. Our
      review of the literature indicates that all behavioural and neuro-imaging studies
      investigating FBA suffer from the shortcoming that they cannot rule out an effect
      of priming. The mere attending to a feature enhances the mandatory processing of
      that feature across the visual field, an effect that is likely to occur in an
      automatic, bottom-up way. Studies that have investigated the feasibility of FBA
      by means of cueing paradigms suggest that the role of top-down processing in FBA
      is limited (e.g. prepare for red). Instead, the actual processing of the stimulus
      is needed to cause the mandatory tuning of responses throughout the visual field.
      We conclude that it is likely that all FBA effects reported previously are the
      result of bottom-up priming. 

PMID- 24018718
TI  - Selection of visual information for lightness judgements by eye movements.
AB  - When judging the lightness of objects, the visual system has to take into account
      many factors such as shading, scene geometry, occlusions or transparency. The
      problem then is to estimate global lightness based on a number of local samples
      that differ in luminance. Here, we show that eye fixations play a prominent role
      in this selection process. We explored a special case of transparency for which
      the visual system separates surface reflectance from interfering conditions to
      generate a layered image representation. Eye movements were recorded while the
      observers matched the lightness of the layered stimulus. We found that observers
      did focus their fixations on the target layer, and this sampling strategy
      affected their lightness perception. The effect of image segmentation on
      perceived lightness was highly correlated with the fixation strategy and was
      strongly affected when we manipulated it using a gaze-contingent display.
      Finally, we disrupted the segmentation process showing that it causally drives
      the selection strategy. Selection through eye fixations can so serve as a simple
      heuristic to estimate the target reflectance. 

PMID- 24018719
TI  - Reach preparation enhances visual performance and appearance.
AB  - We investigated the impact of the preparation of reach movements on visual
      perception by simultaneously quantifying both an objective measure of visual
      sensitivity and the subjective experience of apparent contrast. Using a two-by
      two alternative forced choice task, observers compared the orientation (clockwise
      or counterclockwise) and the contrast (higher or lower) of a Standard Gabor and a
      Test Gabor, the latter of which was presented during reach preparation, at the
      reach target location or the opposite location. Discrimination performance was
      better overall at the reach target than at the opposite location. Perceived
      contrast increased continuously at the target relative to the opposite location
      during reach preparation, that is, after the onset of the cue indicating the
      reach target. The finding that performance and appearance do not evolve in
      parallel during reach preparation points to a distinction with saccade
      preparation, for which we have shown previously there is a parallel temporal
      evolution of performance and appearance. Yet akin to saccade preparation, this
      study reveals that overall reach preparation enhances both visual performance and
      appearance. 

PMID- 24018720
TI  - Modelling eye movements in a categorical search task.
AB  - We introduce a model of eye movements during categorical search, the task of
      finding and recognizing categorically defined targets. It extends a previous
      model of eye movements during search (target acquisition model, TAM) by using
      distances from an support vector machine classification boundary to create
      probability maps indicating pixel-by-pixel evidence for the target category in
      search images. Other additions include functionality enabling target-absent
      searches, and a fixation-based blurring of the search images now based on a
      mapping between visual and collicular space. We tested this model on images from
      a previously conducted variable set-size (6/13/20) present/absent search
      experiment where participants searched for categorically defined teddy bear
      targets among random category distractors. The model not only captured target
      present/absent set-size effects, but also accurately predicted for all conditions
      the numbers of fixations made prior to search judgements. It also predicted the
      percentages of first eye movements during search landing on targets, a
      conservative measure of search guidance. Effects of set size on false negative
      and false positive errors were also captured, but error rates in general were
      overestimated. We conclude that visual features discriminating a target category
      from non-targets can be learned and used to guide eye movements during
      categorical search. 

PMID- 24018721
TI  - Attending to the possibilities of action.
AB  - Actions taking place in the environment are critical for our survival. We review
      evidence on attention to action, drawing on sets of converging evidence from
      neuropsychological patients through to studies of the time course and neural
      locus of action-based cueing of attention in normal observers. We show that the
      presence of action relations between stimuli helps reduce visual extinction in
      patients with limited attention to the contralesional side of space, while the
      first saccades made by normal observers and early perceptual and attentional
      responses measured using electroencephalography/event-related potentials are
      modulated by preparation of action and by seeing objects being grasped correctly
      or incorrectly for action. With both normal observers and patients, there is
      evidence for two components to these effects based on both visual perceptual and
      motor-based responses. While the perceptual responses reflect factors such as the
      visual familiarity of the action-related information, the motor response
      component is determined by factors such as the alignment of the objects with the
      observer's effectors and not by the visual familiarity of the stimuli. In
      addition to this, we suggest that action relations between stimuli can be coded
      pre-attentively, in the absence of attention to the stimulus, and action
      relations cue perceptual and motor responses rapidly and automatically. At
      present, formal theories of visual attention are not set up to account for these
      action-related effects; we suggest ways that theories could be expected to enable
      action effects to be incorporated. 

PMID- 24018722
TI  - Selective visual processing across competition episodes: a theory of task-driven
      visual attention and working memory.
AB  - The goal of this review is to introduce a theory of task-driven visual attention
      and working memory (TRAM). Based on a specific biased competition model, the
      'theory of visual attention' (TVA) and its neural interpretation (NTVA), TRAM
      introduces the following assumption. First, selective visual processing over time
      is structured in competition episodes. Within an episode, that is, during its
      first two phases, a limited number of proto-objects are competitively encoded
      modulated by the current task-in activation-based visual working memory (VWM). In
      processing phase 3, relevant VWM objects are transferred via a short-term
      consolidation into passive VWM. Second, each time attentional priorities change
      (e.g. after an eye movement), a new competition episode is initiated. Third, if a
      phase 3 VWM process (e.g. short-term consolidation) is not finished, whereas a
      new episode is called, a protective maintenance process allows its completion.
      After a VWM object change, its protective maintenance process is followed by an
      encapsulation of the VWM object causing attentional resource costs in trailing
      competition episodes. Viewed from this perspective, a new explanation of key
      findings of the attentional blink will be offered. Finally, a new suggestion will
      be made as to how VWM items might interact with visual search processes. 

PMID- 24018723
TI  - The relationship between visual working memory and attention: retention of
      precise colour information in the absence of effects on perceptual selection.
AB  - We examined the conditions under which a feature value in visual working memory
      (VWM) recruits visual attention to matching stimuli. Previous work has suggested
      that VWM supports two qualitatively different states of representation: an active
      state that interacts with perceptual selection and a passive (or accessory) state
      that does not. An alternative hypothesis is that VWM supports a single form of
      representation, with the precision of feature memory controlling whether or not
      the representation interacts with perceptual selection. The results of three
      experiments supported the dual-state hypothesis. We established conditions under
      which participants retained a relatively precise representation of a parcticular
      colour. If the colour was immediately task relevant, it reliably recruited
      attention to matching stimuli. However, if the colour was not immediately task
      relevant, it failed to interact with perceptual selection. Feature maintenance in
      VWM is not necessarily equivalent with feature-based attentional selection. 

PMID- 24018724
TI  - A biased competition account of attention and memory in Alzheimer's disease.
AB  - The common view of Alzheimer's disease (AD) is that of an age-related memory
      disorder, i.e. declarative memory deficits are the first signs of the disease and
      associated with progressive brain changes in the medial temporal lobes and the
      default mode network. However, two findings challenge this view. First, new model
      based tools of attention research have revealed that impaired selective attention
      accompanies memory deficits from early pre-dementia AD stages on. Second, very
      early distributed lesions of lateral parietal networks may cause these attention
      deficits by disrupting brain mechanisms underlying attentional biased
      competition. We suggest that memory and attention impairments might indicate
      disturbances of a common underlying neurocognitive mechanism. We propose a
      unifying account of impaired neural interactions within and across brain networks
      involved in attention and memory inspired by the biased competition principle. We
      specify this account at two levels of analysis: at the computational level, the
      selective competition of representations during both perception and memory is
      biased by AD-induced lesions; at the large-scale brain level, integration within
      and across intrinsic brain networks, which overlap in parietal and temporal
      lobes, is disrupted. This account integrates a large amount of previously
      unrelated findings of changed behaviour and brain networks and favours a brain
      mechanism-centred view on AD. 

PMID- 24018725
TI  - The role of observers' gaze behaviour when watching object manipulation tasks:
      predicting and evaluating the consequences of action.
AB  - When watching an actor manipulate objects, observers, like the actor, naturally
      direct their gaze to each object as the hand approaches and typically maintain
      gaze on the object until the hand departs. Here, we probed the function of
      observers' eye movements, focusing on two possibilities: (i) that observers' gaze
      behaviour arises from processes involved in the prediction of the target object
      of the actor's reaching movement and (ii) that this gaze behaviour supports the
      evaluation of mechanical events that arise from interactions between the actor's
      hand and objects. Observers watched an actor reach for and lift one of two
      presented objects. The observers' task was either to predict the target object or
      judge its weight. Proactive gaze behaviour, similar to that seen in self-guided
      action-observation, was seen in the weight judgement task, which requires
      evaluating mechanical events associated with lifting, but not in the target
      prediction task. We submit that an important function of gaze behaviour in self
      guided action observation is the evaluation of mechanical events associated with
      interactions between the hand and object. By comparing predicted and actual
      mechanical events, observers, like actors, can gain knowledge about the world,
      including information about objects they may subsequently act upon. 

PMID- 24018726
TI  - Memory and prediction in natural gaze control.
AB  - In addition to stimulus properties and task factors, memory is an important
      determinant of the allocation of attention and gaze in the natural world. One way
      that the role of memory is revealed is by predictive eye movements. Both smooth
      pursuit and saccadic eye movements demonstrate predictive effects based on
      previous experience. We have previously shown that unskilled subjects make highly
      accurate predictive saccades to the anticipated location of a ball prior to a
      bounce in a virtual racquetball setting. In this experiment, we examined this
      predictive behaviour. We asked whether the period after the bounce provides
      subjects with visual information about the ball trajectory that is used to
      programme the pursuit movement initiated when the ball passes through the
      fixation point. We occluded a 100 ms period of the ball's trajectory immediately
      after the bounce, and found very little effect on the subsequent pursuit
      movement. Subjects did not appear to modify their strategy to prolong the
      fixation. Neither were we able to find an effect on interception performance.
      Thus, it is possible that the occluded trajectory information is not critical for
      subsequent pursuit, and subjects may use an estimate of the ball's trajectory to
      programme pursuit. These results provide further support for the role of memory
      in eye movements. 

PMID- 24018727
TI  - Priorities for selection and representation in natural tasks.
AB  - Selecting and remembering visual information is an active and competitive
      process. In natural environments, representations are tightly coupled to task.
      Objects that are task-relevant are remembered better due to a combination of
      increased selection for fixation and strategic control of encoding and/or
      retaining viewed information. However, it is not understood how physically
      manipulating objects when performing a natural task influences priorities for
      selection and memory. In this study, we compare priorities for selection and
      memory when actively engaged in a natural task with first-person observation of
      the same object manipulations. Results suggest that active manipulation of a task
      relevant object results in a specific prioritization for object position
      information compared with other properties and compared with action observation
      of the same manipulations. Experiment 2 confirms that this spatial prioritization
      is likely to arise from manipulation rather than differences in spatial
      representation in real environments and the movies used for action observation.
      Thus, our findings imply that physical manipulation of task relevant objects
      results in a specific prioritization of spatial information about task-relevant
      objects, possibly coupled with strategic de-prioritization of colour memory for
      irrelevant objects. 

PMID- 24018728
TI  - Attention in natural scenes: contrast affects rapid visual processing and
      fixations alike.
AB  - For natural scenes, attention is frequently quantified either by performance
      during rapid presentation or by gaze allocation during prolonged viewing. Both
      paradigms operate on different time scales, and tap into covert and overt
      attention, respectively. To compare these, we ask some observers to detect
      targets (animals/vehicles) in rapid sequences, and others to freely view the same
      target images for 3 s, while their gaze is tracked. In some stimuli, the target's
      contrast is modified (increased/decreased) and its background modified either in
      the same or in the opposite way. We find that increasing target contrast relative
      to the background increases fixations and detection alike, whereas decreasing
      target contrast and simultaneously increasing background contrast has little
      effect. Contrast increase for the whole image (target + background) improves
      detection, decrease worsens detection, whereas fixation probability remains
      unaffected by whole-image modifications. Object-unrelated local increase or
      decrease of contrast attracts gaze, but less than actual objects, supporting a
      precedence of objects over low-level features. Detection and fixation probability
      are correlated: the more likely a target is detected in one paradigm, the more
      likely it is fixated in the other. Hence, the link between overt and covert
      attention, which has been established in simple stimuli, transfers to more
      naturalistic scenarios. 

PMID- 24018729
TI  - Control of the superior colliculus by the lateral prefrontal cortex.
AB  - Several decades of patient, functional imaging and neurophysiological studies
      have supported a model in which the lateral prefrontal cortex (PFC) acts to
      suppress unwanted saccades by inhibiting activity in the oculomotor system.
      However, recent results from combined PFC deactivation and neural recordings of
      the superior colliculus in monkeys demonstrate that the primary influence of the
      PFC on the oculomotor system is excitatory, and stands in direct contradiction to
      the inhibitory model of PFC function. Although erroneous saccades towards a
      visual stimulus are commonly labelled reflexive in patients with PFC damage or
      dysfunction, the latencies of most of these saccades are outside of the range of
      express saccades, which are triggered directly by the visual stimulus.
      Deactivation and pharmacological manipulation studies in monkeys suggest that
      response errors following PFC damage or dysfunction are not the result of a
      failure in response suppression but can best be understood in the context of a
      failure to maintain and implement the proper task set. 

PMID- 24018730
TI  - Evidence for differential top-down and bottom-up suppression in posterior
      parietal cortex.
AB  - When searching for an object, we usually avoid items that are visually different
      from the target and objects or places that have been searched already. Previous
      studies have shown that neural activity in the lateral intraparietal area (LIP)
      can be used to guide this behaviour; responses to task irrelevant stimuli or to
      stimuli that have been fixated previously in the trial are reduced compared with
      responses to potential targets. Here, we test the hypothesis that these reduced
      responses have a different genesis. Two animals were trained on a visual foraging
      task, in which they had to find a target among a number of physically identical
      potential targets (T) and task irrelevant distractors. We recorded neural
      activity and local field potentials (LFPs) in LIP while the animals performed the
      task. We found that LFP power was similar for potential targets and distractors
      but was greater in the alpha and low beta bands when a previously fixated T was
      in the response field. We interpret these data to suggest that the reduced single
      unit response to distractors is a bottom-up feed-forward result of processing in
      earlier areas and the reduced response to previously fixated Ts is a result of
      active top-down suppression. 

PMID- 24018733
TI  - The effect of transcranial direct current stimulation on perception of effort in
      an isolated isometric elbow flexion task.
AB  - The purported ergogenic actions of transcranial direct current stimulation (tDCS)
      applied to motor cortex (M1) on force production and perception of effort were
      investigated using a 10-item numerical rating scale (0-10 NRS) in nonfatiguing
      bouts of a force-matching task utilizing isometric elbow flexion. Using a
      crossover design, 12 healthy volunteers received sham, anodal, and cathodal tDCS
      randomly for 10 min (1.5 mA, 62 MUA/cm2) to the left M1 in a double-blind manner.
      Corticospinal excitability changes were also monitored using transcranial
      magnetic stimulation (TMS) with surface electromyography (sEMG) to monitor both
      motor evoked potentials (MEPs) and force-EMG from right m. biceps brachii and m.
      brachioradialis brachii. No significant differences between the verum and sham
      stimulation were obtained for elbow flexion maximum voluntary force, perception
      of effort, or sEMG. There were also no significant differences in MEP changes for
      the types of tDCS, which is consistent with reports that tDCS excitability
      effects are diminished during ongoing cognitive and motor activities. 

PMID- 24018732
TI  - Epidemiology of diabetes and diabetes complications in the elderly: an emerging
      public health burden.
AB  - Diabetes in the elderly is a growing public health burden. Persons with diabetes
      are living longer and are vulnerable to the traditional microvascular and
      macrovascular complications of diabetes but also at increased risk for geriatric
      syndromes. Peripheral vascular disease, heart disease, and stroke all have a high
      prevalence among older adults with diabetes. Traditional microvascular
      complications such as retinopathy, nephropathy, and neuropathy also frequently
      occur. Unique to this older population is the effect of diabetes on functional
      status. Older adults with diabetes are also more likely to experience geriatric
      syndromes such as falls, dementia, depression, and incontinence. Further studies
      are needed to better characterize those elderly individuals who may be at the
      highest risk of adverse complications from diabetes. 

PMID- 24018731
TI  - Neural chronometry and coherency across speed-accuracy demands reveal lack of
      homomorphism between computational and neural mechanisms of evidence
      accumulation.
AB  - The stochastic accumulation framework provides a mechanistic, quantitative
      account of perceptual decision-making and how task performance changes with
      experimental manipulations. Importantly, it provides an elegant account of the
      speed-accuracy trade-off (SAT), which has long been the litmus test for decision
      models, and also mimics the activity of single neurons in several key respects.
      Recently, we developed a paradigm whereby macaque monkeys trade speed for
      accuracy on cue during visual search task. Single-unit activity in frontal eye
      field (FEF) was not homomorphic with the architecture of models, demonstrating
      that stochastic accumulators are an incomplete description of neural activity
      under SAT. This paper summarizes and extends this work, further demonstrating
      that the SAT leads to extensive, widespread changes in brain activity never
      before predicted. We will begin by reviewing our recently published work that
      establishes how spiking activity in FEF accomplishes SAT. Next, we provide two
      important extensions of this work. First, we report a new chronometric analysis
      suggesting that increases in perceptual gain with speed stress are evident in FEF
      synaptic input, implicating afferent sensory-processing sources. Second, we
      report a new analysis demonstrating selective influence of SAT on frequency
      coupling between FEF neurons and local field potentials. None of these
      observations correspond to the mechanics of current accumulator models. 

PMID- 24018734
TI  - Exploratory survey about dietary supplement use: a hazardous and erratic way to
      improve one's health?
AB  - INTRODUCTION: Dietary supplement (DS) use increased rapidly in recent years.
      However, evidence of benefits of many DSs for healthy users is scarce and may not
      equate with known risks of overdose, drug interaction and recently discovered
      negative long-term effects. This exploratory study aimed to investigate the
      perceptions and motivations of DS users in Lausanne, Switzerland. METHOD: A
      convenience sample (n = 147) was recruited at the entrances of local sales
      points. Data were collected in on-site semistructured interviews that assessed
      dietary supplementation habits. RESULTS: The majority of DSs were all-in-one
      products, containing a mixture of minerals and vitamins, or products containing
      only minerals. Among the 147 users, 72 (49%) used one all-in-one product and 3
      (2%) used two all-in-one products. Thirty-one (21%) consumers did not know for at
      least one product what the purpose of their DS use was. Seventy-five percent of
      participants thought that DS use presents no risk or nearly no risk. Only 49% of
      participants stated that their physicians were informed about their consumption.
      Although men searched more often for potential risks (p <0.001), they turned less
      frequently to health professionals to get this information (p = 0.007).
      DISCUSSION: As in other surveys performed elsewhere, our study shows that, in
      Lausanne (Switzerland), DSs are commonly used as mixed products. Risk perception
      seems generally low among DS users. Physicians should be trained to evaluate
      patients' perceived needs and DS consumption in order to provide good evidence
      based information or to propose alternatives to DS use.

PMID- 24018735
TI  - Hyperpolarized 1H long lived states originating from parahydrogen accessed by rf
      irradiation.
AB  - Hyperpolarization has found many applications in Nuclear Magnetic Resonance (NMR)
      and Magnetic Resonance Imaging (MRI). However, its usage is still limited to the
      observation of relatively fast processes because of its short lifetimes. This
      issue can be circumvented by storing the hyperpolarization in a slowly relaxing
      singlet state. Symmetrical molecules hyperpolarized by Parahydrogen Induced
      Hyperpolarization (PHIP) provide straightforward access to hyperpolarized singlet
      states because the initial parahydrogen singlet state is preserved at almost any
      magnetic field strength. In these systems, which show a remarkably long (1)H
      singlet state lifetime of several minutes, the conversion of the NMR silent
      singlet state to observable magnetization is feasible due to the existence of
      singlet-triplet level anti-crossings. Here, we demonstrate that scaling the
      chemical shift Hamiltonian by rf irradiation is sufficient to transform the
      singlet into an observable triplet state. Moreover, because the application of
      one long rf pulse is only partially converting the singlet state, we developed a
      multiconversion sequence consisting of a train of long rf pulses resulting in
      successive singlet to triplet conversions. This sequence is used to measure the
      singlet state relaxation time in a simple way at two different magnetic fields.
      We show that this approach is valid for almost any magnetic field strength and
      can be performed even in the less homogeneous field of an MRI scanner, allowing
      for new applications of hyperpolarized NMR and MRI. 

PMID- 24018736
TI  - Prevalence of sudden death and out-of-hospital cardiac arrest in infants,
      children, and adolescents. What does it imply?

PMID- 24018737
TI  - Implementation and validation of a fluence pencil kernels model for GaN-based
      dosimetry in photon beam radiotherapy.
AB  - Gallium nitride (GaN), a direct-gap semiconductor that is radioluminescent, can
      be used as a transducer yielding a high signal from a small detecting volume and
      thus potentially suitable for use in small fields and for high dose gradients. A
      common drawback of semiconductor dosimeters with effective atomic numbers higher
      than soft tissues is that their responses depend on the presence of low energy
      photons for which the photoelectric cross section varies strongly with atomic
      number, which may affect the accuracy of dosimetric measurements. To tackle this
      'over-response' issue, we propose a model for GaN-based dosimetry with readout
      correction. The local photon spectrum is calculated by convolving fluence pencil
      kernel spectra with the beam aperture fluence distribution. The response of a GaN
      detector is modelled by combining large cavity theory and small cavity theory for
      the low and high energy components of the local spectrum. Monte Carlo simulations
      are employed for determination of specific correction factors for different GaN
      transducer sizes and irradiation conditions. Some model parameters such as the
      cut-off energy and partitioning energy are discussed. The accuracy of the GaN
      dosimetric response model has been evaluated for tissue phantom ratio experiments
      along the central axis. These experiments have shown that calculated and measured
      GaN responses stay within +/-3% at all depths beyond the build-up depth. The
      calculated GaN response factor is also in good agreement with measured data (+/
      2.5%). The validated model with response compensation improves significantly the
      accuracy of dosimetric measurements: below 2.5% deviation as compared to 13%
      without compensation, for a 10 * 10 cm(2) field, at depth from 1.5 to 22 cm. 

PMID- 24018738
TI  - [The role of neurologists in dementia practice].
AB  - The prevalence of dementia in the aging population is increasing in Japan;
      therefore, expert neurologists are urgently required in dementia practice. We,
      the neurologists, should recognize that our expertise is the core of the medical
      care for dementia and be prepared to lead people in other areas of medical
      professions, including general practitioners and psychiatrists, who are involved
      in dementia management. Expertise of neurologists in different areas, including
      neurological examination, neuropsychology, movement disorders, and neuroimaging,
      are essential, and their skills in managing both acute and chronic medical
      conditions are advantageous. Behavioral neurology, which is a subspecialty of
      neurology, is committed to the care of individuals with cognitive and behavioral
      disturbances and plays a central role in the diagnosis and treatment of all forms
      of dementia. However, there is a huge scarcity of behavioral neurologists in
      Japan, and more of them are needed urgently. In addition, to assign a clear role
      for neurologists in the management of dementia, we should strongly encourage the
      government to involve neurologists in policy-making.

PMID- 24018739
TI  - [Diagnosis and treatment of acute ischemic stroke].
AB  - In Japan, stroke is a major cause of death and serious long-lasting neurological
      disabilities. Recently, the diagnosis and treatment of ischemic stroke has
      changed greatly. 1) Patients with TIA are more susceptible to ischemic stroke,
      and the susceptibility is predicted by the ABCD2score. 2) Brain natriuretic
      peptide (BNP) is a hormone released from the ventricular myocardium; BNP levels
      can predict new atrial fibrillation during hospitalization in patients with acute
      ischemic stroke. 3) In Japan, thrombolysis with intravenous recombinant tissue
      plasminogen activator (rt-PA) for acute ischemic stroke was approved in 2004, and
      the time window was extended up to 4.5 h in 2012. 4) Several novel oral
      anticoagulants (NOAC) have been developed over the last decade; the early
      initiation of NOACs in acute stroke and TIA patients with nonvalvular atrial
      fibrillation may be safe. More evidence-based treatment for stroke in Japanese
      people should be established.

PMID- 24018740
TI  - [Current management of epilepsy].
AB  - Epilepsy is one of the most common neurological disorders. Global neurological
      knowledge is essential for differential diagnosis of epileptic syndromes due to
      the diversity of ictal semiology, causes and syndromes. Neurologists play an
      important role in planning the medical care for patients with epilepsy, as
      medication is the most fundamental therapeutic strategy. Some patients with early
      onset epilepsy require joint care by pediatric neurologists, those with
      intractable epilepsy by neurosurgeons, and those with psychological comorbidity
      by psychiatrists, and neurologists should play a coordinating role. While there
      is a great need for neurologists to participate in epilepsy care, neurologists in
      Japan currently do not participate substantially in the epilepsy management
      system. It is necessary to train more neurologists who can provide epilepsy care
      and conduct basic and clinical research on epilepsy by providing continuous
      education on epilepsy for general neurologists as well as pre- and post-graduate
      medical students. Most of the patients who require long-term treatment experience
      many medical problems and social handicaps, such as adverse effects of
      medication, social stigma, educational disadvantages and difficulties in
      obtaining driver's license. To improve the quality of life of patients with
      epilepsy, it is desirable to build broad medical-social networks participated by
      patients, doctors, neurological nurses, psychologists, social workers, school
      teachers, managers of employment support facilities and care givers.

PMID- 24018741
TI  - [Headache disorders].
AB  - Primary headache disorders such as migraine, tension-type headache, and cluster
      headache are prevalent and disabling neurological disorders. Although most
      headache disorders are largely treatable, they are under-recognized, under
      diagnosed, and under-treated. Many headache sufferers in Japan do not receive
      appropriate and effective health care; hence, the illness, which should be
      relieved, persists and acts as an individual and societal burden. One of the
      barriers most responsible for this is poor awareness of the disorders. For
      lifting the burden, health care must be improved. Education is an essential way
      to resolve these issues at multiple levels. We have a Japanese version of the
      international headache classification and diagnostic criteria II (ICHD-II) and
      guidelines for the management of chronic headaches. Utilization of these
      resources is key for the improvement of headache management in our country. Not
      only neurologists, but also neurosurgeons and other medical specialists are
      participating in headache care in Japan. The Japanese Headache Society and the
      Japanese Society for Neurology should play major roles in health care service,
      education programs, as well as clinical and basic research for headache
      disorders. The road map for realizing our aim on headache treatment is as
      follows: (1) increase the number of units concerning headache in lectures for
      medical students, implement training programs for residents and neurologists, and
      offer continuous medical educations for physicians and neurologists; (2) secure
      more funding for headache research; (3) propagate medical care for headache in
      primary care settings and regional fundamental hospitals; (4) reform the health
      care system for headache and incentivize appropriate compensation for headache
      care in public health insurance; and (5) spread appropriate information on
      medical and socio-ethical issues related to headache for the sufferers and
      citizens. The authors expect that many neurologists have an interest in headache
      and understanding headaches, and better health care for headache disorders will
      bring great benefits for the sufferers.

PMID- 24018742
TI  - [Nystagmus the diagnosis of vertigo and dizziness].
AB  - Vertigo or dizziness is primarily caused by peripheral vestibular disorders, such
      as benign paroxysmal positional vertigo (BPPV) and vestibular neuritis. BPPV can
      be diagnosed from associated positional torsional or direction-changing
      horizontal nystagmus and can be treated with canalith repositioning procedures.
      In contrast, vestibular neuritis and other acute peripheral vestibulopathies can
      be diagnosed from associated unidirectional horizontal nystagmus. Evaluation of
      nystagmus is essential for the diagnosis of peripheral vestibular disorders.
      Vertigo/dizziness caused by disorders in the brainstem or upper cerebellum is
      usually associated with other neurological signs or symptoms, such as motor
      palsy, sensory deficit, dysarthria, ocular motor palsy, and limb ataxia. In
      contrast, vertigo/dizziness caused by disorders in the lower cerebellum is not
      associated with these signs or symptoms; however, truncal ataxia becomes apparent
      in a standing position. Small lesions in the lower cerebellum can rarely cause
      unidirectional horizontal nystagmus directed toward the side of the lesions or
      direction-changing apogeotropic positional nystagmus; both types of nystagmus are
      enhanced when a patient lies on the non-affected side. This positional
      enhancement suggests that the same pathogenetic mechanism is involved in both
      types of nystagmus. The cerebellar lesions may disinhibit both semicircular
      ocular and otolith-ocular reflexes. Semicircular-ocular reflex-dominant
      disinhibitions may result in the ipsilateral horizontal nystagmus, whereas
      otolith-ocular reflex-dominant disinhibitions may result in the direction
      changing apogeotropic positional nystagmus.

PMID- 24018743
TI  - [Peripheral nerve disorders as common diseases].
AB  - Peripheral neuropathy occurs as a component of several common and rare diseases.
      It is heterogeneous in cause, diverse in pathology, and varied in severity. The
      term peripheral neuropathy includes symmetric polyneuropathy, single and multiple
      mononeuropathy, and radiculopathy. The major disorders include diabetic
      neuropathy, alcoholic neuropathy, and carpal tunnel syndrome. The incidence of
      cancer chemotherapy-induced neuropathy has been increasing substantially.
      Although the estimated prevalence of all different peripheral neuropathies is
      considerably high, possibly affecting 10% of the entire population, there is no
      existing systematic epidemiological study on all the aspects of peripheral nerve
      disorders. Neurologists should contribute to both fundamental and symptomatic
      treatments of patients seen in other sections. The important symptomatic
      therapies include treatments for neuropathic pain and autonomic dysfunction.
      There is increasing role for neurologists in treating HIV-related and anti-HIV
      drug-induced neuropathy. More active collaboration with neurologists,
      oncologists, and general physicians is necessary to improve the quality of life
      in patients with peripheral nerve disorders.

PMID- 24018744
TI  - [Old or new medicine? Vitamin B12 and peripheral nerve neuropathy].
AB  - Methylcobalamin is a vitamin B12 analog that is necessary for nervous system
      maintenance. Although methylcobalamin has some positive effects on peripheral
      nervous system disorders, the mechanism through which it affects neurons are not
      entirely known. Recent studies have revealed its intracellular signaling pathway
      and some of its molecular actions on neurons. In this article, I review
      interactions between methylcobalamin and neurons that have been revealed through
      in vitro studies, in vivo studies, and clinical use. Methylcobalamin participates
      in nervous system maintenance through several mechanisms. Methylcobalamin is an
      active form of vitamin B12, and a coenzyme of methionine synthase, which is
      required for DNA and protein methylation. In addition, methylcobalamin
      facilitates neurite outgrowth and inhibits neural apoptosis through the Erk1/2
      and Akt signaling pathways. Treatment with high doses of methylcobalamin
      ameliorates symptoms and negative electrophysiological findings in animal models
      of peripheral nerve neuropathy and in patients with carpal tunnel syndrome and
      amyotrophic lateral sclerosis. Thus, high-dose methylcobalamin has great
      potential for treating nervous system disorders. Further investigations with
      methylcobalamin may help elucidate its mechanisms of action, which may further
      enable us to treat many nervous system disorders.

PMID- 24018745
TI  - [Efficacy and safety of levetiracetam as adjunctive therapy in Japanese children
      with uncontrolled partial-onset seizures: multicenter and open-label study
      (N01223), short term evaluation].
AB  - A multicenter, open-label, single-armed study (N01223) was conducted to evaluate
      efficacy and safety of levetiracetam (LEV) as an add-on therapy in Japanese
      pediatric patients with uncontrolled partial-onset seizures (POS). A total of 73
      children aged 4-15 years (mean+/-SD=10.1+/-3.4 years) were enrolled in the study,
      which consisted of an 8-week baseline period and a 14-week treatment period,
      including a 4-week titration period. A historical placebo control from a pivotal
      overseas pediatric study in POS add-on therapy was used. A 16.3% median percent
      reduction from the baseline in POS was observed in this placebo control.
      Therefore, in the present study, this value (16.3%) was chosen as the predefined
      threshold for the lower limit of the 95% confident interval (95% CI) of the
      median percent reduction from the baseline for LEV. In the present study, the
      percentage reduction (95% CI) in POS during the treatment period was 43.21%
      (26.19-52.14%), indicating a beneficial impact of LEV. The incidences of
      treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were
      82.2% (60/73 cases) and 56.2% (41/73 cases), respectively. The most common TEAEs
      were somnolence, nasopharyngitis, upper respiratory tract infection, and pyrexia.
      Frequent ADRs (more than 3%) were somnolence and feeling jittery. No serious TEAE
      or death was reported during the study. Our results suggested that adjunctive
      therapy with LEV is clinically efficacious and well tolerated in Japanese
      children with uncontrolled POS.

PMID- 24018746
TI  - [Serum of transthyretin as a treatment-responsive biomarker for schizophrenia].
AB  - We investigated the changes in protein profiles of treatment responsive
      biomarkers in three subjects with first-onset schizophrenia using the surface
      enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF
      MS) technology. Our results showed that eight protein peaks were down-regulated
      or up-regulated during the acute phase, and returned toward the control values
      during the recovery phase. In particular, a 13,761Da protein peak was markedly
      down-regulated during the acute phase, and returned during the recovery phase.
      This protein was identified as unmodified transthyretin using two-dimensional
      electrophoresis followed by peptide mass fingerprinting based on matrix assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
      However, we failed to show transthyretin changes with the treatment using enzyme
      linked immunosorbent assay (ELISA) and two-dimensional electrophoresis. The
      distinction between unmodified and modified subtypes of transthyretin was
      difficult with these methods because of similar molecular weights and isoelectric
      points in these subtypes. The present study showed that the application of SELDI
      TOF-MS technology has higher precision for the distinction of detailed molecular
      weight than conventional proteomics techniques such as ELISA and two-dimensional
      electrophoresis. The dynamic changes in transthyretin have been reported to be
      associated with acute-psychosis condition; the present study suggested that
      unmodified transthyretin has the potential to be a treatment responsive biomarker
      for schizophrenia.

PMID- 24018747
TI  - Ultrahigh thermoelectric performance by electron and phonon critical scattering
      in Cu2 Se1-x Ix.
AB  - Iodine-doped Cu2 Se shows a significantly improved thermoelectric performance
      during phase transitions by electron and phonon critical scattering, leading to a
      dramatic increase in zT by a factor of 3-7 times culminating in zT values of 2.3
      at 400 K. 

PMID- 24018749
TI  - Transiting the molecular potential energy surface along low energy pathways: the
      TRREAT algorithm.
AB  - The Transition Rapidly exploring Random Eigenvector Assisted Tree (TRREAT)
      algorithm is introduced to perform searches along low curvature pathways on a
      potential energy surface (PES). The method combines local curvature information
      about the PES with an iterative Rapidly exploring Random Tree algorithm (LaValle,
      Computer Science Department, Iowa State University, 1998, TR98-11) that quickly
      searches high-dimensional spaces for feasible pathways between local minima.
      Herein, the method is applied to identifying conformational changes of molecular
      systems using Cartesian coordinates while avoiding a priori definition of
      collective variables. We analyze the pathway identification problem for alanine
      dipeptide, cyclohexane and glycine using nonreactive and reactive forcefields. We
      show how TRREAT-identified pathways can be used as valuable input guesses for
      double-ended methods such as the Nudged Elastic Band when ascertaining transition
      state energies. This method can be utilized to improve/extend the reaction
      databases that lie at the core of automatic chemical reaction mechanism generator
      software currently developed to build kinetic models of chemical reactions.

PMID- 24018748
TI  - Remote cardioprotection by transfer of coronary effluent from ischemic
      preconditioned rabbit heart preserves mitochondrial integrity and function via
      adenosine receptor activation.
AB  - BACKGROUND: Coronary effluent from an isolated perfused heart undergoing ischemic
      preconditioning can be transferred to precondition another naive isolated heart.
      We investigated the effects of this effluent on mitochondrial integrity and
      function following a global infarct model of ischemia/reperfusion and the role of
      adenosine in this model of remote preconditioning. METHODS AND RESULTS: Coronary
      effluent from isolated perfused rabbit hearts was collected prior to (control
      effluent) and during three cycles of 5-min ischemia and 10-min reperfusion (IPC
      effluent). Adenosine concentration was significantly increased in IPC effluent
      (2.6 +/- 1.1 MUM) versus control effluent (0.21 +/- 0.06 MUM, P < 0.01). Infarct
      size (% necrotic LV mass) after 30-min global ischemia and 90-min reperfusion was
      significantly reduced in hearts preconditioned with IPC effluent (IPC(eff), 23 +/
      7 %) and control effluent supplemented with 2.5 MUM exogenous adenosine (C(eff)+
      2.5 MUM ADO, 25 +/- 10 %) when compared to control effluent perfused hearts
      (C(eff), 41 +/- 8 %, P < 0.05). Compared to C(eff) mitochondria, IPC(eff)
      mitochondria had preserved complex I/State3 and complex IV/State 3 respiration
      and outer membrane integrity, and reduced cytochrome c release. In contrast,
      C(eff) + 2.5 MUM ADO mitochondria had improved state 2 respiration and coupling
      to oxidative phosphorylation, reduced reactive oxygen species production and
      preserved outer membrane integrity. Administration of adenosine receptor blocker
      8-(p-sulfophenyl)theophylline abolished the infarct limiting effect (46 +/- 7 %)
      and the mitochondrial integrity and function preservation of IPC effluent.
      CONCLUSION: Remote cardioprotection by IPC effluent preserves mitochondrial
      integrity and function in an adenosine receptor dependent mechanism, and although
      infarct size reduction can be mimicked by adenosine, IPC effluent contains
      additional factor(s) contributing to modulation of the mitochondrial response to
      ischemia/reperfusion injury.

PMID- 24018750
TI  - Application of gas pycnometry for the density measurement of freeze-dried
      products.
AB  - Gas pycnometry is applied to determine the density of solid materials. The
      analysis of lyophilisates is particularly challenging because of their porous
      structure. In this study, the density of raw materials and freeze-dried products
      was determined using different pycnometric methodologies and gases [helium (He),
      nitrogen (N2 ), sulfur hexafluoride]. The number of purges was set to 60
      independent of the gas used. Intact and ground lyophilisates were examined, and
      major differences were found between use of He and N2 . For example, the density
      of sucrose lyophilisates measured using He remained almost constant before (1.51
      g/cm(3) ) and after (1.52 g/cm(3) ) grinding. In contrast, the density of a
      sucrose lyophilisate before grinding determined with N2 was 1.33 g/cm(3) . On the
      basis of MUCT and scanning electron microscopy pictures, it appears likely that
      the majority of pores are interconnected, with only a small fraction of closed
      pores. Helium is able to penetrate deep into the freeze-dried matrix and is
      supposedly absorbed by the material. The N2 molecules were not able to penetrate
      closed pores; therefore, the skeletal density of an intact lyophilisate was
      determined. Reproducibility of the established method was verified, and freeze
      dried orally disintegrating tablets of different compositions were analyzed.

PMID- 24018751
TI  - Where is the beef? Waist circumference is more highly correlated with BMI and
      total body fat than with abdominal visceral fat in children.

PMID- 24018752
TI  - Multidetector CT imaging of post-robot-assisted laparoscopic radical
      prostatectomy complications.
AB  - BACKGROUND: Robot-assisted laparoscopic radical prostatectomy (RALRP) is
      currently accepted as the preferred minimally invasive surgical treatment for
      localised prostate cancer, with optimal oncologic and functional results. Despite
      growing surgical experience, reduced postoperative morbidity and hospital stays,
      RALRP-related complications may occur, which are severe in 5-7 % of patients and
      sometimes require reoperation. Therefore, in hospitals with an active urologic
      surgery, urgent diagnostic imaging is increasingly requested to assess suspected
      early complications following RALRP surgery. METHODS: Based upon our experience,
      this pictorial review discusses basic principles of the surgical technique, the
      optimal multidetector CT (MDCT) techniques to be used in the postoperative
      urologic setting, the normal postoperative anatomy and imaging appearances.
      RESULTS: Afterwards, we review and illustrate the varied spectrum of RALRP
      related complications including haemorrhage, urinary leaks, anorectal injuries,
      peritoneal changes, surgical site infections, abscess collections and
      lymphoceles, venous thrombosis and port site hernias. CONCLUSION: Knowledge of
      surgical procedure details, appropriate MDCT acquisition techniques, and
      familiarity with normal postoperative imaging appearances and possible
      complications are needed to correctly perform and interpret early post-surgical
      imaging studies, particularly to identify those occurrences that require
      prolonged in-hospital treatment or surgical reintervention. TEACHING POINTS: *
      Robot-assisted laparoscopic radical prostatectomy allows minimally invasive
      surgery of localised cancer * Urologic surgeons may request urgent imaging to
      assess suspected postoperative complications * Main complications include
      haemorrhage, urine leaks, anorectal injuries, infections and lymphoceles *
      Correct multidetector CT techniques allow identifying haematomas, active bleeding
      and extravasated urine * Imaging postoperative complications is crucial to assess
      the need for surgical reoperation.

PMID- 24018753
TI  - Invited Commentary: "Event-based versus process-based informed consent to address
      scientific evidence and uncertainties in ionising medical imaging" by Recchia et
      al.

PMID- 24018754
TI  - Response to invited commentary: "Event-based versus process-based informed
      consent to address scientific evidence and uncertainties in ionizing medical
      imaging" by Recchia et al.

PMID- 24018755
TI  - Clinical impact of (18)F-FDG PET-CT in recurrent stage III/IV melanoma: a
      tertiary centre Specialist Skin Cancer Multidisciplinary Team (SSMDT) experience.
AB  - OBJECTIVES: To assess the clinical impact of (18)F-fluorodeoxyglucose positron
      emission tomography-computed tomography (FDG PET-CT) compared with contrast
      enhanced computed tomography (CECT) in patients referred via the Specialist Skin
      Cancer Multidisciplinary Team (SSMDT) with recurrent stage III/IV malignant
      melanoma (MM). METHODS: Forty-five patients were referred for further evaluation
      with FDG PET-CT. Findings on FDG PET-CT were compared with prior CECT and the
      clinical impact on subsequent management decisions was determined
      retrospectively. A major clinical impact was defined as a change in treatment
      plan resulting from identification of additional sites of disease or by
      characterisation of indeterminate findings on prior imaging. A minor impact was
      defined as confirmation of known sites of disease as identified on prior CECT.
      RESULTS: Fifty-one PET-CT examinations were performed. FDG PET-CT had a major
      clinical impact in 21 cases (41.2 %), of which 18 examinations were performed in
      patients with proven or suspected stage IV MM. FDG PET-CT had a minor impact in
      23 cases (45.1 %), and there were five false-positive cases (9.8 %) and two false
      negative cases (3.9 %). CONCLUSION: FDG PET-CT is an effective tool in recurrent
      stage III/IV MM with a significant clinical impact on management decisions in
      patients who are appropriately referred via the highly specialised forum of the
      SSMDT. KEY POINTS: * FDG PET-CT is an effective tool in recurrent stage III/IV
      malignant melanoma. * FDG PET-CT has a significant clinical impact on management
      decisions. * Effective use of FDG PET-CT is via referral from the Specialist Skin
      Cancer Multidisciplinary Team.

PMID- 24018756
TI  - Improving quality improvement for cardiopulmonary resuscitation.

PMID- 24018757
TI  - Peripheral input and its importance for central sensitization.
AB  - Many pain states begin with damage to tissue and/or nerves in the periphery,
      leading to enhanced transmitter release within the spinal cord and central
      sensitization. Manifestations of this central sensitization are windup and long
      term potentiation. Hyperexcitable spinal neurons show reduced thresholds, greater
      evoked responses, increased receptive field sizes, and ongoing stimulus
      independent activity; these changes probably underlie the allodynia,
      hyperalgesia, and spontaneous pain seen in patients. Central sensitization is
      maintained by continuing input from the periphery, but also modulated by
      descending controls, both inhibitory and facilitatory, from the midbrain and
      brainstem. The projections of sensitized spinal neurons to the brain, in turn,
      alter the processing of painful messages by higher centers. Several mechanisms
      contribute to central sensitization. Repetitive activation of primary afferent C
      fibers leads to a synaptic strengthening of nociceptive transmission. It may also
      induce facilitation of non-nociceptive Abeta fibers and nociceptive Adelta
      fibers, giving rise to dynamic mechanical allodynia and mechanical hyperalgesia.
      In postherpetic neuralgia and complex regional pain syndrome, for example, these
      symptoms are maintained and modulated by peripheral nociceptive input. Diagnosing
      central sensitization can be particularly difficult. In addition to the medical
      history, quantitative sensory testing and functional magnetic resonance imaging
      may be useful, but diagnostic criteria that include both subjective and objective
      measures of central augmentation are needed. Mounting evidence indicates that
      treatment strategies that desensitize the peripheral and central nervous systems
      are required. These should generally involve a multimodal approach, so that
      therapies may target the peripheral drivers of central sensitization and/or the
      central consequences.

PMID- 24018758
TI  - The evolving science of cochlear implants.

PMID- 24018759
TI  - Feasibility of remote administration of the Fundamentals of Laparoscopic Surgery
      (FLS) skills test.
AB  - BACKGROUND: Fundamentals of Laparoscopic Surgery (FLS) certification testing
      currently is offered at accredited test centers or at select surgical
      conferences. Maintaining these test centers requires considerable investment in
      human and financial resources. Additionally, it can be challenging for
      individuals outside North America to become FLS certified. The objective of this
      pilot study was to assess the feasibility of remotely administering and scoring
      the FLS examination using live videoconferencing compared with standard onsite
      testing. METHODS: This parallel mixed-methods study used both FLS scoring data
      and participant feedback to determine the barriers to feasibility of remote
      proctoring for the FLS examination. Participants were tested at two accredited
      FLS testing centers. An official FLS proctor administered and scored the FLS exam
      remotely while another onsite proctor provided a live score of participants'
      performance. Participant feedback was collected during testing. Interrater
      reliabilities of onsite and remote FLS scoring data were compared using
      intraclass correlation coefficients (ICCs). Participant feedback was analyzed
      using modified grounded theory to identify themes for barriers to feasibility.
      RESULTS: The scores of the remote and onsite proctors showed excellent interrater
      reliability in the total FLS (ICC 0.995, CI [0.985-0.998]). Several barriers led
      to critical errors in remote scoring, but most were accompanied by a solution
      incorporated into the study protocol. The most common barrier was the chain of
      custody for exam accessories. CONCLUSION: The results of this pilot study suggest
      that remote administration of the FLS has the potential to decrease costs without
      altering test-taker scores or exam validity. Further research is required to
      validate protocols for remote and onsite proctors and to direct execution of
      these protocols in a controlled environment identical to current FLS test
      administration.

PMID- 24018760
TI  - Fundoplication versus medical management of gastroesophageal reflux disease:
      systematic review and meta-analysis.
AB  - BACKGROUND: Medical, endoscopic, and open/laparoscopic surgical methods are used
      to treat gastroesophageal reflux disease (GERD). This study aimed to perform a
      systematic review of randomized controlled trials comparing medical and surgical
      treatments of GERD in adult patients. METHODS: For the study, MEDLINE and EMBASE
      (1980-2012) were searched. Two reviewers independently assessed methodologic
      aspects and extracted data from eligible studies, focusing on patient-relevant
      outcomes. The primary outcomes were health-related and GERD-specific quality-of
      life aspects. Standardized mean differences (SMDs) between treatment groups were
      calculated and combined using random-effect meta-analysis. RESULTS: The study
      identified 11 publications reporting on 7 trials comparing surgical (open or
      laparoscopic) and medical treatment of GERD. Meta-analysis of both quality-of
      life aspects showed a pooled-effect estimate in favor of fundoplication (SMD
      0.18; 95 % confidence interval [CI] 0.01-0.35; SMD 0.33; 95 % CI 0.13-0.54).
      Heartburn and regurgitation were less frequent after surgical intervention.
      However, a considerable proportion of patients still needed antireflux medication
      after fundoplication. Nevertheless, the surgical patients were significantly more
      satisfied with their symptom control and showed higher satisfaction with the
      treatment received. CONCLUSIONS: This systematic review showed that surgical
      management of GERD is more effective than medical management with respect to
      patient-relevant outcomes in the short and medium term. However, long-term
      studies still are needed to determine whether antireflux surgery is an equivalent
      alternative to lifelong medical treatment.

PMID- 24018761
TI  - SAGES guidelines for minimally invasive treatment of adrenal pathology.

PMID- 24018763
TI  - Response to glucose tolerance testing and solid high carbohydrate challenge:
      comparison between Roux-en-Y gastric bypass, vertical sleeve gastrectomy, and
      duodenal switch.
AB  - BACKGROUND: Hyperinsulinemic hypoglycemia is common after Roux-en-Y gastric
      bypass (RYGB) and may result in weight regain. The purpose of our investigation
      was to compare the effect of RYGB, vertical sleeve gastrectomy (VSG), and
      duodenal switch (DS) on insulin and glucose response to carbohydrate challenge.
      METHODS: Patients meeting National Institutes of Health criteria for bariatric
      surgery selected their bariatric procedure after evaluation and education in this
      prospective nonrandomized study. Preoperatively and at 6, 9, and 12 months'
      follow-up, patients underwent blood draw to determine levels of fasting glucose,
      fasting insulin, glycated hemoglobin (HbA1c), C-peptide, and 2-h oral glucose
      challenge test. Homoeostatic Model Assessment (HOMA)-IR, fasting to 1-h and 1- to
      2-h ratios of glucose and insulin, were calculated. Statistical analysis was
      performed using ANOVA and Student's paired t test. All procedures were performed
      via a laparoscopic technique at a single institution. RESULTS: Data from a total
      of 38 patients (13 RYGB, 12 VSG, 13 DS) were available for analysis. At baseline,
      all groups were similar; the only statistically significant difference was that
      DS patients had a higher preoperative weight and body mass index (BMI). All
      operations caused weight loss (BMI 47.7 +/- 10-30.7 +/- 6.4 kg/m(2) in RYGB; 45.7
      +/- 8.5-31.1 +/- 5.5 kg/m(2) in VSG; 55.9 +/- 11.4-27.5 +/- 5.6 kg/m(2) in DS),
      reduction of fasting glucose, and improved insulin sensitivity. RYGB patients had
      a rapid rise in glucose with an accompanying rise in 1-h insulin to a level that
      exceeded preoperative levels. This was followed by a rapid decrease in glucose
      level. In comparison, DS patients had a lower increase in glucose and 1-h
      insulin, and the lowest HbA1c. These differences were statistically significant
      at various data points. For VSG, the results were intermediary. CONCLUSIONS:
      Compared to gastric bypass, DS results in greater weight loss and improves
      insulin sensitivity and glucose homeostasis without causing a hyperinsulinemic
      response. Because the response to challenge after VSG is intermediary, pyloric
      preservation alone cannot account for this difference.

PMID- 24018764
TI  - Clinical significance of intraperitoneal air on computed tomography scan after
      endoscopic submucosal dissection in patients with gastric neoplasms.
AB  - BACKGROUND: Perforations are major complications of endoscopic gastric resection,
      including endoscopic submucosal dissection (ESD), and are generally detected on
      chest radiography following ESD. We hypothesized that a small amount of free air,
      defined as "intraperitoneal air," would not be noted on chest radiography. In
      this study we aimed to determine how often intraperitoneal air is seen on a
      computed tomography (CT) scan after ESD and to evaluate the association between
      clinical factors and intraperitoneal air. METHODS: A total of 147 patients who
      underwent ESD for gastric neoplasms were analyzed between September 2009 and
      September 2010. Patients underwent both chest radiography and noncontrast CT
      scans. Intraperitoneal air on the CT scan was stratified by the amount of gas as
      follows: grade I, free air localized along the outside of the gastric wall; grade
      II, free air in the lesser sac; and grade III, free air in front of the liver.
      RESULTS: Intraperitoneal air was detected in 56 patients (38.1 %) by an abdominal
      CT scan, whereas free air was noted in 2 patients (1.4 %) by chest radiography.
      Most patients with intraperitoneal air (96.4 %, 54/56) were grade I or II and 3.6
      % (2/56) were grade III. Abdominal pain was more frequent in the intraperitoneal
      air group (32.1 %, 18/56) than in the no intraperitoneal air group (17.6 %,
      16/91; P = 0.042). Tumor location at the lesser curvature was more frequent in
      the intraperitoneal air group (66.1 %, 37/56) than in the no intraperitoneal air
      group (38.5 %, 35/91; P < 0.001). Fever, use of antibiotics, duration of hospital
      stay, C-reactive protein level, white blood cell count, complete resection, and
      local recurrence did not differ between the two groups. All patients who had
      intraperitoneal air recovered completely with medical treatment. CONCLUSION:
      Intraperitoneal air after gastric ESD occurred unexpectedly frequently. However,
      a small amount of intraperitoneal air on a CT scan does not cause clinically
      significant complications.

PMID- 24018765
TI  - Wilhelm Weinberg's early contribution to segregation analysis.
AB  - Wilhelm Weinberg (1862-1937) is a largely forgotten pioneer of human and medical
      genetics. His name is linked with that of the English mathematician G. H. Hardy
      in the Hardy-Weinberg law, pervasive in textbooks on population genetics since it
      expresses stability over generations of zygote frequencies AA, Aa, aa under
      random mating. One of Weinberg's signal contributions, in an article whose
      centenary we celebrate, was to verify that Mendel's segregation law still held in
      the setting of human heredity, contrary to the then-prevailing view of William
      Bateson (1861-1926), the leading Mendelian geneticist of the time. Specifically,
      Weinberg verified that the proportion of recessive offspring genotypes aa in
      human parental crossings Aa * Aa (that is, the segregation ratio for such a
      setting) was indeed p=1/4. We focus in a nontechnical way on his procedure,
      called the simple sib method, and on the heated controversy with Felix Bernstein
      (1878-1956) in the 1920s and 1930s over work stimulated by Weinberg's article.

PMID- 24018762
TI  - Guidelines for the management of hiatal hernia.

PMID- 24018766
TI  - Functional genetics in the post-genomics era: building a better roadmap in
      Drosophila.
AB  - In this commentary, Rob Kulathinal describes two articles from the Perrimon lab,
      each describing a new online resource that can assist geneticists with the design
      of their RNA interference (RNAi) experiments. Hu et al.'s "UP-TORR: online tool
      for accurate and up-to-date annotation of RNAi reagents" and "FlyPrimerBank: An
      online database for Drosophila melanogaster gene expression analysis and
      knockdown evaluation of RNAi reagents" are published, respectively, in this
      month's issues of GENETICS and G3. 

PMID- 24018769
TI  - Surgical options for the management of ischemic cardiomyopathy.
AB  - OPINION STATEMENT: Novel surgical alternatives and the refinement of conventional
      surgical therapies for the treatment of ischemic cardiomyopathy are in constant
      evolution. Current approaches involve the determined application of the
      appropriateness criteria for CABG surgery, the extension of mitral valve repair
      to complex patients with ischemic cardiomyopathy, finding appropriate patients
      who might benefit from surgical ventricular reconstruction, and surgical attempts
      to regenerate lost or damaged myocardium with transplanted stem cells. The
      refinement of surgical techniques and the medical optimization of candidates for
      surgery remain a cornerstone of management for patients with complex heart
      disease like ischemic cardiomyopathy. The horizon is bright for patients
      suffering from this condition and concentrated research efforts by groups such as
      the NHLBI-sponsored Cardiothoracic Surgery Network will have a major impact on
      the future of patients with heart disease.

PMID- 24018771
TI  - Design of electrochemical detection of thiols based on the cleavage of the
      disulfide bond coupled with thionine modified gold nanoparticle-assisted
      amplification.
AB  - A new strategy for the electrochemical detection of thiols based on the disulfide
      cleavage combined with gold nanoparticle (AuNP) assisted signal amplification and
      an AuNP and graphene (GR) and ionic liquid (IL) modified carbon paste electrode
      (AuNP/GR/CILE). A superior detection limit of 0.4 pM toward glutathione could be
      achieved. 

PMID- 24018772
TI  - Utility of integrated pharmacogenomic testing to support the treatment of major
      depressive disorder in a psychiatric outpatient setting.
AB  - OBJECTIVE: The objective was to evaluate the potential benefit of an integrated,
      five-gene pharmacogenomic test and interpretive report (GeneSight) for the
      management of psychotropic medications used to treat major depression in an
      outpatient psychiatric practice. METHODS: The open-label study was divided into
      two groups. In the first (unguided) group (n = 113), pharmacogenomic information
      was not shared until all participants completed the study. In the second (guided)
      group (n = 114), the pharmacogenomic report was provided to physicians for
      clinical use. Three depression ratings, the 17-item Hamilton Rating Scale for
      Depression (HAMD-17), the Quick Inventory of Depressive Symptomatology -
      Clinician Rated (QIDS-C16), and the Patient Health Questionnaire (PHQ-9), were
      collected at baseline, and at 2, 4, and 8 weeks. RESULTS: The guided group
      experienced greater percent improvement in depression scores from baseline on all
      three depression instruments (HAMD-17, P < 0.0001; QIDS-C16, P < 0.0001; PHQ-9, P
      < 0.0001) compared with the unguided group. Eight-week response rates were higher
      in the guided group than in the unguided group on all three measurements (HAMD
      17, P = 0.03; QIDS-C16, P = 0.005; PHQ-9, P = 0.01). Eight-week QIDS-C16
      remission rates were higher in the guided group (P = 0.03). Participants in the
      unguided group who at baseline were prescribed a medication that was most
      discordant with their genotype experienced the least improvement compared with
      other unguided participants (HAMD-17, P = 0.007). Participants in the guided
      group and on a baseline medication most discordant with their genotype showed the
      greatest improvement compared with the unguided cohort participants (HAMD-17, P =
      0.01). CONCLUSION: These findings replicate previous studies and demonstrate
      significantly improved depression outcomes with use of GeneSight, an integrated,
      multigenetic pharmacogenomic testing platform.

PMID- 24018773
TI  - Pharmacogenetics of ABC and SLC transporters in metastatic colorectal cancer
      patients receiving first-line FOLFIRI treatment.
AB  - OBJECTIVE: Membrane transporters are widely recognized as important determinants
      of drug disposition and response, generating increasing interest on the
      pharmacological implications of their genetic variations. The aim of this study
      was to elucidate the predictive/prognostic role of ATP-binding cassette (ABC) and
      solute carrier (SLC) protein polymorphisms on irinotecan (FOLFIRI regimen)
      outcome. PATIENTS AND METHODS: A total of 250 White metastatic colorectal cancer
      patients homogenously treated with a first-line FOLFIRI regimen were genotyped
      for a panel of variants in five transporter genes. The primary study endpoints
      were the response rate (partial or complete response), overall survival, and time
      to progression. Toxicity was considered a secondary endpoint. Irinotecan
      pharmacokinetic data of 71 patients were used for polymorphism functional
      analysis. RESULTS: Two variants of the ABCG2 (-15622C>T, rs7699188) gene were
      found to be predictive (P < 0.01) of the response rate. High-order relationships
      of ABC/SLC markers with previously investigated genetic (UGT1A1 polymorphisms)
      and nongenetic (primary tumor site) factors that helped determine the response
      rate were highlighted. A prognostic effect of the ABCB1 rs2032582 variant on
      patient overall survival emerged (P = 0.0074). The ABCG2 rs7699788 variant was
      also seen to be associated with grade 3-4 nonhematological toxicity (P = 0.0012).
      The ABCG2 (-15622C>T, rs7699188) and ABCB1 (rs2032582) polymorphisms were not
      found to be associated with pharmacokinetic parameters. CONCLUSION: This study
      showed that ABC/SLC polymorphisms have a crucial contribution toward the FOLFIRI
      outcome. This could represent a further step toward personalized therapy.

PMID- 24018767
TI  - Mapping yeast transcriptional networks.
AB  - The term "transcriptional network" refers to the mechanism(s) that underlies
      coordinated expression of genes, typically involving transcription factors (TFs)
      binding to the promoters of multiple genes, and individual genes controlled by
      multiple TFs. A multitude of studies in the last two decades have aimed to map
      and characterize transcriptional networks in the yeast Saccharomyces cerevisiae.
      We review the methodologies and accomplishments of these studies, as well as
      challenges we now face. For most yeast TFs, data have been collected on their
      sequence preferences, in vivo promoter occupancy, and gene expression profiles in
      deletion mutants. These systematic studies have led to the identification of new
      regulators of numerous cellular functions and shed light on the overall
      organization of yeast gene regulation. However, many yeast TFs appear to be
      inactive under standard laboratory growth conditions, and many of the available
      data were collected using techniques that have since been improved. Perhaps as a
      consequence, comprehensive and accurate mapping among TF sequence preferences,
      promoter binding, and gene expression remains an open challenge. We propose that
      the time is ripe for renewed systematic efforts toward a complete mapping of
      yeast transcriptional regulatory mechanisms. 

PMID- 24018774
TI  - Roles of accessory proteins for heterotrimeric G-protein in the development of
      cardiovascular diseases.
AB  - Signal processing via heterotrimeric G-proteins is one of the most widely used
      systems for signal transfer across the cell membrane. This signaling system
      regulates most physiological and pathophysiological processes in mammals and is
      therefore the primary target of many pharmaceutical agents. The heterotrimeric G
      protein signaling system includes the G-protein-coupled receptor (GPCR),
      heterotrimeric G-proteins, and effectors. The G-proteins are activated by the
      GPCR to mediate a signal to effector molecules. However, other players in this
      system that regulate the activation status of heterotrimeric G-proteins
      independently of GPCR have been identified. Such accessory proteins for
      heterotrimeric G-protein can provide additional signal input to the G-protein
      signaling system, or may act as alternative binding partners of G-protein
      subunits serving as yet unknown roles in cells. It has been reported that this
      class of proteins is expressed in the cardiovascular system and contributes to
      signal integration involved in the various diseases. This review provides an
      overview of the current understanding of accessory proteins for heterotrimeric G
      proteins in their 4 functional subsets, including guanine nucleotide exchange
      factors (GEFs), guanine nucleotide dissociation inhibitors (GDIs), GTPase
      activating proteins (GAPs), and Gbetagamma-interacting proteins, and discusses
      their roles in the development of cardiovascular diseases. Better understanding
      of these components may contribute new insight into the complex network of
      molecules governing GPCR signaling in the cardiovascular system. 

PMID- 24018775
TI  - Drug-eluting coronary stents for left main coronary artery disease. Is too much
      as bad as too little?

PMID- 24018777
TI  - Treatment of acne scars with fractional CO2 laser at 1-month versus 3-month
      intervals: an intra-individual randomized controlled trial.
AB  - BACKGROUND: Treatment of acne scars with ablative fractional CO2 laser appears to
      be an effective and well-tolerated treatment. However, so far the influence of
      treatment interval has not been evaluated. OBJECTIVE: To evaluate whether
      treatment of acne scars with fractional CO2 laser resurfacing at 1-month interval
      achieves better results with no difference in the occurrence of adverse effects,
      than treatment given at 3-months interval. METHODS: Patients (n = 13) with
      symmetrical atrophic acne scars on right and left sides of the mid-face and lower
      face were randomized to two fractional CO2 laser treatments at 1-month versus 3
      month intervals. Blinded on-site evaluations were performed 1 and 6 months after
      the last treatment on 10-point scales. Endpoints were scar atrophy, patient
      satisfaction, and adverse effects. RESULTS: Pre-operatively, acne scars were
      moderately atrophic (5.86 +/- 1.87). After treatment acne scars appeared with
      less atrophy on both treated sides 1 month postoperatively (1-month interval 1.96
      +/- 1.23, P < 0.0001; 3-months interval 1.82 +/- 1.08, P = 0.0006) and 6 months
      postoperatively (1-month interval 1.56 +/- 1.24, P = 0.0021; 3-months interval
      1.33 +/- 1.66, P = 0.0002). The treatment interval did not influence the
      improvement of scar atrophy at any time postoperatively (P = 0.81). Patients were
      moderately and equally satisfied with the treatment result on facial sides (P =
      0.93). Postoperative adverse effects were minor and not influenced by the
      treatment interval. CONCLUSIONS: Fractional CO2 laser resurfacing improves
      atrophic acne scars and a treatment interval of either 1-month or 3-months does
      not seem to influence the improvement of scar atrophy nor the occurrence of
      postoperative adverse effects.

PMID- 24018776
TI  - Worldwide isotope ratios of the Fukushima release and early-phase external dose
      reconstruction.
AB  - Measurements of radionuclides (RNs) in air made worldwide following the Fukushima
      accident are quantitatively compared with air and soil measurements made in
      Japan. Isotopic ratios RN:(137)Cs of (131)I, (132)Te, (134,136)Cs, are correlated
      with distance from release. It is shown, for the first time, that both within
      Japan and globally, ratios RN:(137)Cs in air were relatively constant for
      primarily particle associated radionuclides ((134,136)Cs; (132)Te) but that
      (131)I shows much lower local (<80 km) isotope ratios in soils relative to
      (137)Cs. Derived isotope ratios are used to reconstruct external dose rate during
      the early phase post-accident. Model "blind" tests show more than 95% of
      predictions within a factor of two of measurements from 15 sites to the north,
      northwest and west of the power station. It is demonstrated that generic isotope
      ratios provide a sound basis for reconstruction of early-phase external dose
      rates in these most contaminated areas.

PMID- 24018778
TI  - Diagnosis and treatment of iron deficiency in medical inpatients at a Swiss
      tertiary university referral hospital: a retrospective observational cohort study
      of clinical practice.
AB  - BACKGROUND: Iron deficiency anaemia is a common disease with a prevalence of up
      to 19.2% in populations at risk. However, the prevalence of iron deficiency (ID)
      in hospitalised patients is not well known. The aims of this retrospective,
      observational cohort study were to evaluate the current diagnostic procedures
      for, and treatment of, ID as well as to estimate the prevalence of undiagnosed ID
      in hospitalised patients at the division of internal medicine in a Swiss tertiary
      university referral centre. METHODS: Within a study period of 6 months, data from
      all patients hospitalised at the division of internal medicine were analysed for
      the presence of anaemia (defined as haemoglobin levels for males <130 g/l and for
      females <120 g/l) and ID (ferritin <15 ug/l or ferritin <50 ug/l and transferrin
      saturation <20%). RESULTS: A total of 2,781 hospitalisation cases were analysed
      (2,251 unique patients, male 55.5%, mean age 66.4 years). In 2,267 cases (81.5%)
      results of a red blood cell count were available. In 329 cases (14.5%) iron
      parameters (IP) were determined and 45 (13.7%) cases / unique patients with ID
      were detected. Among the remaining 1,938 cases without IP determination,
      statistical estimation predicted 103 (56-329) undiagnosed ID cases. In ID
      patients, the most prevalent diagnosis was heart failure (24.4%). Of these
      patients, 72.7% had haemorrhage-facilitating drugs on hospital admission or
      discharge. CONCLUSION: Iron deficiency is common in internal medicine and up to
      two-thirds of cases may not be diagnosed. Every seventh patient who had iron
      parameters analysed was iron deficient and two-thirds of patients with ID were
      treated with intravenous iron.

PMID- 24018779
TI  - Evaluation of a highly skin permeable low-molecular-weight protamine conjugated
      epidermal growth factor for novel burn wound healing therapy.
AB  - We evaluated the laser induced burn wound healing efficacy of a recombinant low
      molecular-weight protamine conjugated epidermal growth factor (rLMWP-EGF). rLMWP
      EGF was prepared by genetically combining LMWP with the N-terminal sequence of
      EGF; we obtained a homogeneous modified EGF without reduced biological activity.
      Because of the protein transduction domain of LMWP, rLMWP-EGF showed enhanced
      drug penetration across artificial skin constructs and excised mouse skin layers
      versus EGF and showed significantly improved burn wound healing efficacy, with
      accelerated wound closure and minimized eschar and scar formation, compared with
      EGF or no treatment. Histological examination also revealed that rLMWP-EGF
      permeated through the intact skin around the wound and facilitated residual
      epithelial cell proliferation in an integrated manner to reform an intact
      epidermis. Radiofrequency microwound formation was effective for reducing large
      hypertrophic scars formed after severe laser burning by collagen remodeling but
      rLMWP-EGF did not show a meaningful synergistic effect in burn scar reduction.
      However, rLMWP-EGF was helpful for forming skin with a more normal appearance and
      texture. Thus, rLMWP-EGF demonstrated therapeutic potential as a novel topical
      burn wound healing drug with no obvious toxic effect.

PMID- 24018780
TI  - Accurate and efficient modeling of the detector response in small animal multi
      head PET systems.
AB  - In fully three-dimensional PET imaging, iterative image reconstruction techniques
      usually outperform analytical algorithms in terms of image quality provided that
      an appropriate system model is used. In this study we concentrate on the
      calculation of an accurate system model for the YAP-(S)PET II small animal
      scanner, with the aim to obtain fully resolution- and contrast-recovered images
      at low levels of image roughness. For this purpose we calculate the system model
      by decomposing it into a product of five matrices: (1) a detector response
      component obtained via Monte Carlo simulations, (2) a geometric component which
      describes the scanner geometry and which is calculated via a multi-ray method,
      (3) a detector normalization component derived from the acquisition of a planar
      source, (4) a photon attenuation component calculated from x-ray computed
      tomography data, and finally, (5) a positron range component is formally
      included. This system model factorization allows the optimization of each
      component in terms of computation time, storage requirements and accuracy. The
      main contribution of this work is a new, efficient way to calculate the detector
      response component for rotating, planar detectors, that consists of a GEANT4
      based simulation of a subset of lines of flight (LOFs) for a single detector head
      whereas the missing LOFs are obtained by using intrinsic detector symmetries.
      Additionally, we introduce and analyze a probability threshold for matrix
      elements of the detector component to optimize the trade-off between the matrix
      size in terms of non-zero elements and the resulting quality of the reconstructed
      images. In order to evaluate our proposed system model we reconstructed various
      images of objects, acquired according to the NEMA NU 4-2008 standard, and we
      compared them to the images reconstructed with two other system models: a model
      that does not include any detector response component and a model that
      approximates analytically the depth of interaction as detector response
      component. The comparisons confirm previous research results, showing that the
      usage of an accurate system model with a realistic detector response leads to
      reconstructed images with better resolution and contrast recovery at low levels
      of image roughness. 

PMID- 24018782
TI  - [Anticoagulant therapy update in cerebrovascular diseases].

PMID- 24018781
TI  - Different aspects of sartan + calcium antagonist association compared to the
      single therapy on inflammation and metabolic parameters in hypertensive patients.
AB  - This study aims to evaluate the effects of an angiotensin receptor blocker
      (ARB)/calcium channel blocker combination on blood pressure control, lipid
      profile, insulin sensitivity, and inflammation markers. We randomized 276
      hypertensive patients to olmesartan 20 mg, amlodipine 10 mg, or a single pill
      containing an olmesartan/amlodipine combination 20/5 mg for 12 months. We
      evaluated the following: body weight, systolic and diastolic blood pressure,
      fasting plasma glucose, fasting plasma insulin (FPI), M value, lipid profile,
      adiponectin (ADN), high sensitivity C-reactive protein (Hs-CRP), monocyte
      chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor
      1beta (MIP-1beta). Olmesartan/amlodipine combination better reduced blood
      pressure, FPI, homeostasis model assessment index, and increased M value and ADN
      compared to olmesartan and amlodipine monotherapies. Olmesartan/amlodipine
      significantly decreased Hs-CRP, MCP-1, and MIP-1beta. In this multicenter,
      randomized, double-blind, clinical study, ARB/calcium antagonist combination
      resulted to be more effective than single monotherapies in reducing blood
      pressure, in improving insulin sensitivity, and in reducing inflammation
      parameters in patients with stage I essential hypertension.

PMID- 24018783
TI  - [Retrospective analysis of the effectiveness of Yokukansan(Japanese Herbal
      Medicine, TJ-54)in the treatment of delirium following acute stroke].
AB  - The aim of our retrospective study was to investigate the efficacy and safety of
      Yokukansan(TJ-54)in treating delirium during hospitalization following acute
      stroke. We retrospectively analyzed the patients 1)who were admitted to our
      single stroke center from January 2010 to December 2011 due to acute stroke
      within four days from onset, 2)who presented with delirium after admission, which
      was diagnosed according to the Diagnostic and Statistical Manual of Mental
      Disorders-IV-Text Revision(DSM-IV-TR)criteria, and 3)who received 2.5g of
      Yokukansan(TJ-54)three times a day for treating delirium and which was continued
      until discharge or until onset of adverse effects. We investigated the patient's
      baseline characteristics, the period of Yokukansan treatment, history of using of
      another psychotropic drug and complications. We used the Delirium Rating
      Scale(DRS)to assess delirium state before and at five days after initiation of
      Yokukansan(TJ-54). We analyzed 77 patients retrospectively. Their mean age was
      79.3 years old, and 48 patients(62%)were female. Median DRS score was improved
      from 15(interquartile range;14-18)to 8(interquartile;6-13), statistically
      significant(p<0.01)at five days after the initiation of Yokukansan(TJ-54). The
      median period of Yokukansan(TJ-54)treatment was seven days. There were no
      patients who received psychotropic drugs or who were suspected of developing
      oversedation due to Yokukansan(TJ-54). In our study, delirium symptoms following
      acute stroke improved after Yokukansan(TJ-54)treatment. A randomized controlled
      trial is needed to establish the effectiveness of Yokukansan(TJ-54)in delirium
      after stroke. 

PMID- 24018784
TI  - [Azygos anterior cerebral artery aneurysm in a patient with Noonan syndrome].
AB  - Noonan syndrome(NS)is a common, clinically and genetically heterogeneous
      condition characterized by distinctive facial features, short stature, congenital
      heart disease, and other comorbidities. However, there have been only a few case
      reports of cerebrovascular abnormalities in patients with NS. Especially, the
      cases of intracranial aneurysms with NS are very rare. In addition, comorbidities
      of azygos anterior cerebral artery(ACA)and NS have not been reported before now.
      We encountered such a rare case of azygos ACA unruptured aneurysm in patient with
      NS. The case was 64-year-old woman with NS complaining of gait disturbance. The
      three-dimensional CT angiography(3D-CTA)showed azygos ACA and an unruptured
      saccular aneurysm at the distal end of the A2 segment. An operation for this
      aneurysm was performed. We reviewed clinical features of NS with cerebrovascular
      disease such as aneurysm.

PMID- 24018786
TI  - [Revascularization with the Penumbra Aspiration System for symptomatic subacute
      in-stent occlusion after carotid artery stenting: a case report].
AB  - Carotid in-stent thrombosis can cause thromboembolic events although it is a rare
      complication of carotid artery stenting(CAS). We present a successful case of
      percutaneous mechanical thrombectomy for symptomatic subacute in-stent
      thrombosis. A 64-year-old man was hospitalized for the treatment of a cerebral
      infarction presenting with dysarthria and left upper extremity weakness.
      Following sufficient medical management including dual anti-platelet therapy, CAS
      was performed because cerebral angiograms showed severe and long-segment right
      internal carotid artery(ICA)stenosis. Although the stenosis was resolved, right
      cerebral infarction presented with progressive left hemiparesis 12 days after
      CAS. Emergency cerebral angiograms revealed right ICA occlusion due to in-stent
      thrombosis. Rapid revascularization with percutaneous mechanical thrombectomy of
      the in-stent occlusion was performed using the Penumbra Aspiration System because
      a microguidewire could not pass through the occlusion. Post-procedural angiogram
      revealed recanalization of the right ICA, and the patient was free from
      neurological events after the last procedure. The evaluation and treatment of
      peri-procedural in-stent thrombosis following CAS must be prompt and aggressive
      for prevention of catastrophic events. Percutaneous mechanical thrombectomy is a
      useful tool for rapid treatment of acute or subacute in-stent thrombosis after
      CAS. 

PMID- 24018785
TI  - [Surgical indication for two cases of symptomatic Rathke's cleft cysts with
      spontaneous involution].
AB  - In cases of symptomatic Rathke's cleft cysts with headache, visual disturbance,
      and endocrinopathy, we choose operations. But, the effects of operations are
      different according to the symptoms. Recently, there are some reports of Rathke's
      cleft cysts with spontaneous involution, and we need to reconsider the surgical
      indication for symptomatic Rathke's cleft cysts. We also had two cases of
      suspected Rathke's cleft cysts with spontaneous disappearance. Taking these
      experiences into account, we may spend time on detecting the operative indication
      for symptomatic Rathke's cleft cysts with the symptom such as headache. But, we
      should evaluate pituitary function by hormone-loading tests immediately to
      consider the operative indication for cases with symptoms such as endocrine
      dysfunction. 

PMID- 24018787
TI  - [Subarachnoid hemorrhage caused by dissection of the basilar artery: a case
      report].
AB  - We report a case of subarachnoid hemorrhage, which was caused by dissection of
      the basilar artery during treatment for diabetes mellitus. The patient was a 60
      year-old male who consulted our hospital complaining of sudden-onset of a severe
      headache. Head CT scan showed subarachnoid hemorrhage around the basilar artery,
      but 3D-CT angiography revealed no abnormality. The basilar artery was shown to be
      normal during cerebral angiography on Day 1. However, in retrospect pseudolumen
      of the basilar artery was suspected in the proximal portion of the branching
      point of the anterior inferior cerebellar artery. During a second cerebral
      angiography on Day 17, blood pressure elevated to 185/83mmHg and 30 minutes later
      this patient's consciousness deteriorated to 10 points of the GCS(E4, V2, M4).
      The double lumen in the basilar artery was identified around the branching point
      of the anterior inferior cerebellar artery. Head MRI on the same day showed
      intramural hemorrhage of the basilar artery as a high intensity lesion. Head MRI
      on Day 18 revealed multiple cerebellar infarctions in the region of the bilateral
      anterior inferior cerebellar arteries. His consciousness recovered to almost
      normal by reducing the blood pressure. Transient gait disturbance also recovered
      thereafter. Head MRI on Day 90 indicated disappearance of the intramural
      hemorrhage in the basilar artery. It was important to reduce the blood pressure
      to prevent recurrence of the arterial dissection. 

PMID- 24018788
TI  - [A case of unruptured large aneurysm in the distal with difficult classification
      of vascular structure: successful direct clipping with bypass surgery].

PMID- 24018789
TI  - [Required knowledge for Spinal Surgeon(1)Neurological Examinations].

PMID- 24018790
TI  - [(11)Treatment of glioma. State-of-the-art: a series of 1,036 surgeries on 944
      cases].
AB  - The author's own experience of 1,036 surgeries on 944 glioma cases in the period
      between 1993 to 2011(mostly at the University Hospital Zurich)are presented.
      Glioblastoma cases were the most frequent, amounting to ca. 30% of cases as is
      shown in Fig.4A. They were operated on 1.3 times on the average but the most
      frequent repetition-surgery was in cases with fibrillary astrocytomas(Fig.1), as
      these tended to transform into secondary glioblastomas which needed surgery
      again. The latter amounting to 10% of glioblastoma cases that had transformed
      from astrocytoma in the course of 3.8 years on the average(Fig.4B). With modern
      "state-of-the-art" treatment of glioma(Table), survival term for glioblastoma
      patients has clearly improved. This can be seen by comparison of figures between
      generations(Fig.4C, D):Prof. Krayenbuhl's era(macrosurgery+/-RT), Prof.
      Yasargil's era(microsurgery+RT)and the most recent part of my
      treatment(microsurgery+ "state-of-the-art" treatment). Representative cases of
      various glioma are presented in which "cured" cases of glioblastoma are also
      included.

PMID- 24018791
TI  - Synthetic cannabinoids: a new frontier of designer drugs.

PMID- 24018792
TI  - In vitro and in silico studies of MDM2/MDMX isoforms predict Nutlin-3A
      sensitivity in well/de-differentiated liposarcomas.
AB  - The molecular marker of well-differentiated/de-differentiated liposarcomas is
      MDM2 gene amplification coupled with protein overexpression and wild-type TP53.
      MDMX is a recently identified MDM2 homolog and its presence in this tumor is
      unexplored. Our aim was to investigate the role of full-length MDM2 and MDMX
      proteins and their isoforms in surgical specimens of well-differentiated/de
      differentiated liposarcomas in view of Nutlin-3A (a MDM2 inhibitor) treatment.
      Frozen and matched formalin-fixed, paraffin-embedded material from surgical
      specimens was examined by means of: (1) fluorescence in situ hybridization to
      determine MDM2 and MDMX gene copy numbers; (2) RT-PCR and densitometry to analyze
      alternative splicing forms of mdm2 and mdmx; (3) immunoblotting and
      immunohistochemistry to assess the corresponding translated proteins; and (4) in
      vitro and in silico assays to determine their affinity for Nutlin-3A. All these
      cases showed MDM2 gene amplification with an MDMX disomic pattern. In all cases,
      the full-length mdm2 transcript was associated with the mdm2-b transcript, with
      ratios ranging from 0.07 to 5.6, and both were translated into protein; mdmx and
      mdmx-s were co-transcripted, with ratios ranging from 0.1 to 5.6. MDMX-S was
      frequently more upregulated than MDMX at both transcriptional and protein level.
      Each case showed different amounts of mdm2, mdm2-b, mdmx, and mdmx-s transcripts
      and the corresponding proteins. In vitro assays showed that Nutlin-3A was
      ineffective against MDM2-B and was unable to disrupt the MDMX/TP53 and MSMX
      S/TP53 complexes. Molecular simulations confirmed these in vitro findings by
      showing that MDM2 has high Nutlin-3A affinity, followed by MDMX-S, MDMX, and MDM2
      B. Nutlin-3A is predicted to be a good therapeutic option for well
      differentiated/de-differentiated liposarcomas. However, our findings predict
      heterogeneous responses depending on the relative expression of mdm2, mdm2-b,
      mdmx, and mdmx-s transcripts and proteins. 

PMID- 24018793
TI  - Age of the donor reduces the ability of human adipose-derived stem cells to
      alleviate symptoms in the experimental autoimmune encephalomyelitis mouse model.
AB  - There is a significant clinical need for effective therapies for primary
      progressive multiple sclerosis, which presents later in life (i.e., older than 50
      years) and has symptoms that increase in severity without remission. With
      autologous mesenchymal stem cell therapy now in the early phases of clinical
      trials for all forms of multiple sclerosis (MS), it is necessary to determine
      whether autologous stem cells from older donors have therapeutic effectiveness.
      In this study, the therapeutic efficacy of human adipose-derived mesenchymal stem
      cells (ASCs) from older donors was directly compared with that of cells from
      younger donors for disease prevention. Mice were induced with chronic
      experimental autoimmune encephalomyelitis (EAE) using the myelin oligodendrocyte
      glycoprotein35-55 peptide and treated before disease onset with ASCs derived from
      younger (<35 years) or older (>60 years) donors. ASCs from older donors failed to
      ameliorate the neurodegeneration associated with EAE, and mice treated with older
      donor cells had increased central nervous system inflammation, demyelination, and
      splenocyte proliferation in vitro compared with the mice receiving cells from
      younger donors. Therefore, the results of this study demonstrated that donor age
      significantly affects the ability of human ASCs to provide neuroprotection,
      immunomodulation, and/or remyelination in EAE mice. The age-related therapeutic
      differences corroborate recent findings that biologic aging occurs in stem cells,
      and the differences are supported by evidence in this study that older ASCs,
      compared with younger donor cells, secrete less hepatocyte growth factor and
      other bioactive molecules when stimulated in vitro. These results highlight the
      need for evaluation of autologous ASCs derived from older patients when used as
      therapy for MS. 

PMID- 24018794
TI  - Isolation of human adipose-derived stromal cells using laser-assisted liposuction
      and their therapeutic potential in regenerative medicine.
AB  - Harvesting adipose-derived stromal cells (ASCs) for tissue engineering is
      frequently done through liposuction. However, several different techniques exist.
      Although third-generation ultrasound-assisted liposuction has been shown to not
      have a negative effect on ASCs, the impact of laser-assisted liposuction on the
      quality and differentiation potential of ASCs has not been studied. Therefore,
      ASCs were harvested from laser-assisted lipoaspirate and suction-assisted
      lipoaspirate. Next, in vitro parameters of cell yield, cell viability and
      proliferation, surface marker phenotype, osteogenic differentiation, and
      adipogenic differentiation were performed. Finally, in vivo bone formation was
      assessed using a critical-sized cranial defect in athymic nude mice. Although
      ASCs isolated from suction-assisted lipoaspirate and laser-assisted lipoaspirate
      both successfully underwent osteogenic and adipogenic differentiation, the cell
      yield, viability, proliferation, and frequency of ASCs (CD34(+)CD31(-)CD45(-)) in
      the stromal vascular fraction were all significantly less with laser-assisted
      liposuction in vitro (p < .05). In vivo, quantification of osseous healing by
      micro-computed tomography revealed significantly more healing with ASCs isolated
      from suction-assisted lipoaspirate relative to laser-assisted lipoaspirate at the
      4-, 6-, and 8-week time points (p < .05). Therefore, as laser-assisted
      liposuction appears to negatively impact the biology of ASCs, cell harvest using
      suction-assisted liposuction is preferable for tissue-engineering purposes. 

PMID- 24018795
TI  - Cell-free protein expression based on extracts from CHO cells.
AB  - Protein expression systems are widely used in biotechnology and medicine for the
      efficient and economic production of therapeutic proteins. Today, cultivated
      Chinese hamster ovary (CHO) cells are the market dominating mammalian cell-line
      for the production of complex therapeutic proteins. Despite this outstanding
      potential of CHO cells, no high-yield cell-free system based on translationally
      active lysates from these cells has been reported so far. To date, CHO cell
      extracts have only been used as a foundational research tool for understanding
      mRNA translation (Lodish et al., 1974; McDowell et al., 1972). In the present
      study, we address this fact by establishing a novel cell-free protein expression
      system based on extracts from cultured CHO cells. Lysate preparation, adaptation
      of in vitro reaction conditions and the construction of particular expression
      vectors are considered for high-yield protein production. A specific in vitro
      expression vector, which includes an internal ribosome entry site (IRES) from the
      intergenic region (IGR) of the Cricket paralysis virus (CrPV), has been
      constructed in order to obtain optimal performance. The IGR IRES is supposed to
      bind directly to the eukaryotic 40S ribosomal subunit thereby bypassing the
      process of translation initiation, which is often a major bottleneck in cell-free
      systems. The combination of expression vector and optimized CHO cell extracts
      enables the production of approximately 50 ug/mL active firefly luciferase within
      4 h. The batch-type cell-free coupled transcription-translation system has the
      potential to perform post-translational modifications, as shown by the
      glycosylation of erythropoietin. Accordingly, the system contains
      translocationally active endogenous microsomes, enabling the co-translational
      incorporation of membrane proteins into biological membranes. Hence, the
      presented in vitro translation system is a powerful tool for the fast and
      convenient optimization of expression constructs, the specific labeling of
      integral membrane proteins and the cell-free production of posttranslationally
      modified proteins.

PMID- 24018796
TI  - Circulating endothelial cells in pediatric renal transplant recipients.
AB  - BACKGROUND: An increase in the number of circulating endothelial cells (CEC)
      indicates endothelial damage and the risk of cardiovascular disease. The aim of
      our study was to investigate the association of CEC with various clinical
      parameters in pediatric renal transplant recipients. METHODS: CEC, defined as
      CD45(-)CD146(+), were enumerated by flow cytometry from the peripheral blood of
      50 pediatric renal transplant recipients and 20 healthy controls. Clinical
      parameters, including renal function tests, fasting blood glucose, serum
      cholesterol and triglyceride, cyclosporine A (CsA) (trough and 2nd-hour) and
      tacrolimus (tac) trough blood levels and their association with CEC numbers were
      analyzed. RESULTS: CEC numbers of patients were higher than those of controls
      (respectively, 128 +/- 89 cells/ml (42-468 cells/ml), 82 +/- 33 cells/ml (32-137
      cells/ml), p = 0.024). There was a statistically significant negative correlation
      between CEC numbers and glomerular filtration rate (GFR) (r = -0.300, p = 0.012).
      There was also a statistically positive association between CEC numbers and
      transplant duration as well as cyclosporine trough level (respectively, r =
      0.397, p = 0.004, r = 0.714, p = 0.004). CEC numbers in patients on tac and CsA
      were similar (p = 0.716). CONCLUSIONS: Our results demonstrate that renal
      transplant recipients with high CsA trough blood level, longer transplant
      duration, and lower GFR, are at greater risk of developing endothelial damage.

PMID- 24018797
TI  - Parent-child and spousal relationships in families with a young child with end
      stage renal disease.
AB  - BACKGROUND: End-stage renal disease (ESRD) leads to the need for dialysis and
      renal transplantation (Tx). Peritoneal dialysis (PD) of young children is
      normally performed at home by the parents and affects the whole family. We
      studied the coping of families with a young child with ESRD by interviewing the
      parents of 19 children. METHODS: The spousal and parent-child relationships were
      assessed by using the Psychosocial Assessment of Childhood Experiences (PACE) and
      the Brief Measure of Expressed Emotion, respectively. A control group of 22
      families with a healthy child was used for the parent-child relationship
      evaluation. RESULTS: The spousal relationship at the start of PD was good or
      fairly good in most of the families and remained good in half of the families
      following renal Tx. Lack of support from close relatives and renal Tx were
      associated with a poorer relationship quality. Almost all parents expressed much
      or fairly much emotional warmth towards the child throughout the study, but there
      was a trend towards increased criticism over time. No differences in the degree
      of expressed warmth or criticism were noted between the index parents and
      controls. CONCLUSIONS: Overall, the study families appeared to cope well despite
      the serious illness of their child and the demands of the treatments.

PMID- 24018799
TI  - Letter to the editor: Complications of total knee arthroplasty: standardized list
      and definitions of The Knee Society.

PMID- 24018798
TI  - Reproducibility study of four-dimensional flow MRI of arterial and portal venous
      liver hemodynamics: influence of spatio-temporal resolution.
AB  - PURPOSE: To evaluate influence of variation in spatio-temporal resolution and
      scan-rescan reproducibility on three-dimensional (3D) visualization and
      quantification of arterial and portal venous (PV) liver hemodynamics at four
      dimensional (4D) flow MRI. METHODS: Scan-rescan reproducibility of 3D hemodynamic
      analysis of the liver was evaluated in 10 healthy volunteers using 4D flow MRI at
      3T with three different spatio-temporal resolutions (2.4 * 2.0 * 2.4 mm(3), 61.2
      ms; 2.5 * 2.0 * 2.4 mm(3), 81.6 ms; 2.6 * 2.5 * 2.6 mm(3), 80 ms) and thus
      different total scan times. Qualitative flow analysis used 3D streamlines and
      time-resolved particle traces. Quantitative evaluation was based on maximum and
      mean velocities, flow volume, and vessel lumen area in the hepatic arterial and
      PV systems. RESULTS: 4D flow MRI showed good interobserver variability for
      assessment of arterial and PV liver hemodynamics. 3D flow visualization revealed
      limitations for the left intrahepatic PV branch. Lower spatio-temporal resolution
      resulted in underestimation of arterial velocities (mean 15%, P < 0.05). For the
      PV system, hemodynamic analyses showed significant differences in the velocities
      for intrahepatic portal vein vessels (P < 0.05). Scan-rescan reproducibility was
      good except for flow volumes in the arterial system. CONCLUSION: 4D flow MRI for
      assessment of liver hemodynamics can be performed with low interobserver
      variability and good reproducibility. Higher spatio-temporal resolution is
      necessary for complete assessment of the hepatic blood flow required for clinical
      applications.

PMID- 24018800
TI  - How sensitive and specific is urinalysis 'dipstick' testing for detection of
      hyperglycaemia and ketosis? An audit of findings from coronial autopsies.
AB  - AIMS: Biochemical analysis of glucose and ketones in the vitreous humour obtained
      at post-mortem examination is representative of the levels in the blood prior to
      death. Elevated levels can be indicative of conditions including diabetic
      ketoacidosis, which can be a cause for unexpected death. A rapid screening test
      for such conditions can be performed during the autopsy through urinalysis using
      test strips (urine 'dipstick' testing). The aim of this study was to assess the
      utility of urinalysis testing for post-mortem detection of derangements of
      glucose and ketone levels. METHODS: The results of vitreous biochemical analysis
      and urinalysis were collated from 188 forensic autopsy cases. RESULTS: A vitreous
      glucose result of above 10 mmol/L was regarded as high. When this was compared to
      urinalysis results it was found that any urinalysis result above negative had a
      sensitivity of 0.83 and a specificity of 0.93. A vitreous ketone level of above 5
      mmol/L was regarded as significantly elevated; a urinalysis result above negative
      had a sensitivity of 1, but a specificity of 0.12. CONCLUSIONS: Urinalysis
      ('dipstick' testing) for glucose has a good sensitivity and specificity for high
      vitreous glucose levels, which are regarded as indicative of pathological
      hyperglycaemia during life. It was found that urine testing for ketones either
      has an excellent sensitivity with low specificity or a poor sensitivity with a
      good specificity; however, this finding has to be viewed in the context of
      uncertainty of the biochemical level of significant ketosis.

PMID- 24018801
TI  - Epithelial-mesenchymal transition phenotype is associated with patient survival
      in small intestinal adenocarcinoma.
AB  - AIMS: We investigated the clinical significance of epithelial-mesenchymal
      transition (EMT) phenotype in 184 small intestinal adenocarcinomas (SIACs) based
      on the expression pattern of EMT-related proteins in cancer cells. METHODS:
      Immunohistochemistry for epithelial (E-cadherin) and mesenchymal (vimentin and
      fibronectin) markers were performed and cases of SIAC were classified into four
      subtypes of EMT: complete type (E-cadherin-, vimentin+ and/or fibronectin+), wild
      type (E-cadherin+, vimentin-, fibronectin-), incomplete 1 type (hybrid type; E
      cadherin+, vimentin+ and/or fibronectin+), and incomplete 2 type (null type; E
      cadherin-, vimentin-, fibronectin-). RESULTS: We identified 19 (10.3%) cases of
      complete EMT type, 86 (46.7%) cases of wild type and 79 (43%) cases of incomplete
      EMT type [hybrid type, 22 (12%) cases; null type, 57 (31%) cases]. Complete EMT
      phenotype showed a significant association with undifferentiated histology
      (p<0.001). Overall survival of SIAC patients with complete EMT phenotype was
      significantly shorter than those of patients with incomplete (p=0.001) and wild
      (p<0.001) types. In multivariate analysis, complete EMT phenotype was an
      independent prognostic factor in SIAC patients (hazard ratio 2.3; 95% confidence
      interval 1.15-4.6; p=0.019). CONCLUSION: Complete EMT phenotype stratifies a
      specific group representing a poor clinical outcome in patients with SIAC.

PMID- 24018802
TI  - Alpha thalassaemia due to non-deletional mutations on the -3.7 alpha globin
      fusion gene: laboratory diagnosis and clinical importance.
AB  - AIMS: Alpha (alpha) thalassaemia may be caused by large deletions of the alpha
      globin gene(s), or rarely, non-deletional mutations. Both types of mutations may
      co-exist, and if located on the same allele (alpha), produce a reproductive risk
      of hydrops fetalis. We illustrate how clinical-laboratory correlation and
      accurate alpha gene sequencing are essential in identifying such patients.
      METHOD: Nine asymptomatic patients with -alpha thalassaemia trait were noted to
      have significant microcytosis that was insufficiently explained by a single alpha
      deletion. Hence alpha1 and alpha2 globin gene sequencing were performed, which
      detected a non-deletional mutation in all patients. A new set of alpha1 specific
      primers were designed for separate sequencing of the alpha1 gene and the -alpha
      fusion gene, respectively, so that the non-deletional mutation could be localised
      to the correct allele. RESULTS: In six of nine patients tested, the non
      deletional mutation was on the alpha1 globin gene. In three patients the mutation
      was located on the -alpha fusion gene. The latter group functionally has an alpha
      allele (alphaalpha/-) with a reproductive risk for Hb Barts hydrops fetalis.
      CONCLUSION: Non-deletional mutations can occur on the alpha globin gene or a
      fusion gene such as the -alpha allele. Identification and accurate localisation
      of these mutations is important as this can have significant reproductive
      implications.

PMID- 24018803
TI  - Acetylation status of P53 and the expression of DBC1, SIRT1, and androgen
      receptor are associated with survival in clear cell renal cell carcinoma
      patients.
AB  - AIMS: Recently, the important role of silent mating type information regulation 2
      homolog 1 (SIRT1) and deleted in breast cancer 1 (DBC1) in human cancer has been
      extensively studied and their role has been closely related with the control of
      P53 and androgen receptor (AR) functions. However, their role in clear cell renal
      cell carcinoma (CRCC) is still unknown. METHODS: We evaluated the expression of
      SIRT1, P53, acetylated-P53, DBC1 and AR and their prognostic significance in 200
      CRCC patients. RESULTS: The expression of SIRT1, P53, DBC1, and AR significantly
      correlated with each other and all of them predicted shorter overall survival
      (OS), relapse-free survival (RFS), and cancer-specific survival (CSS). In
      contrast, the expression of acetylated-P53 predicted favourable OS, RFS, and CSS.
      Combined expression pattern of acetylated-P53 and P53 (Ac-P53/P53) also closely
      correlated with survival of CRCC patients. Multivariate analysis revealed DBC1,
      acetylated-P53, and Ac-P53/P53 expression as independent prognostic indicators
      for OS and RFS, and Ac-P53 expression as an independent prognostic indicator for
      CSS. CONCLUSIONS: This study demonstrates that the acetylation status of P53 and
      the expression of SIRT1, DBC1, and AR could be new prognostic indicators for CRCC
      and suggest that SIRT1-P53 and DBC1-AR related pathways could be new therapeutic
      targets for the treatment of CRCC.

PMID- 24018804
TI  - The analysis of microsatellite instability in extracolonic gastrointestinal
      malignancy.
AB  - Microsatellite instability (MSI) is a genetic feature of sporadic and familial
      cancers of multiple sites and is related to defective mismatch repair (MMR)
      protein function. Lynch syndrome (LS) is a familial form of MMR deficiency that
      may present with a spectrum of MSI positive cancers including gastrointestinal
      (GI) malignancies. The incidence of high level MSI (MSI-H) in colorectal
      carcinoma is well defined in both familial and sporadic cases and these tumours
      portend a better overall prognosis in colorectal carcinoma (CRC). There are
      certain morphological features that suggest MSI-H CRC and international
      guidelines have been established for the evaluation of MSI in CRC. The prevalence
      and morphological features of extracolonic GI MSI-H tumours are less well
      documented. Furthermore, it is unclear whether the guidelines for the assessment
      of MSI in CRC are appropriate for application to extracolonic GI malignancies.
      This review aims to summarise the recent literature on MSI in extracolonic LS
      related GI tract malignancies with special attention to the assessment of the MMR
      system by evaluation of specific microsatellite markers and/or
      immunohistochemical evaluation of MMR protein expression. The reported prevalence
      of sporadic and LS-related MSI-H tumours along with their associated unique
      morphological patterns and related prognostic or therapeutic implications will be
      discussed.

PMID- 24018805
TI  - Intraductal carcinoma of the prostate: the whole story.
AB  - Intraductal carcinoma of the prostate (IDC-P) is characterised by proliferation
      of malignant secretory cells that markedly expand prostatic ducts and acini. Its
      morphological features and diagnostic criteria have been refined in recent
      studies. Its molecular characteristics have also been increasingly elucidated.
      IDC-P is strongly associated with high grade and high volume invasive prostate
      cancer and unfavourable clinical outcomes. Therefore, it is critical to recognise
      and report IDC-P, especially in prostate biopsies where the clinical implications
      of the diagnosis are greatest. IDC-P has to be distinguished from several other
      prostate lesions with similar histological appearance. The distinction between
      IDC-P and high grade prostatic intraepithelial neoplasia is most important as
      they have drastically different implications for patient management. IDC-P is an
      uncommon finding in prostate biopsies, and is even rarer as an isolated finding
      without concomitant prostate cancer in biopsies. However, patients with isolated
      IDC-P in biopsies are recommended for either definitive treatment or immediate
      repeat biopsy. This article will review the historical aspect, diagnostic
      criteria, molecular genetics, and clinical significance of IDC-P.

PMID- 24018806
TI  - Metastatic gastrointestinal stromal tumour of the ileum with dual primary c-KIT
      missence mutations.

PMID- 24018807
TI  - Four cases of primary malignant perivascular epithelioid cell tumour of the
      liver.

PMID- 24018808
TI  - Immunophenotypic analysis of ovarian endometrioid adenocarcinoma: correlation
      with KRAS mutation and the presence of endometriosis.
AB  - AIMS: The relationship between endometriosis and ovarian endometrioid
      adenocarcinoma (OEC) is well recognised but it is unclear whether endometriosis
      positive and negative OECs develop via similar pathogenetic mechanisms.
      MATERIALS: Sixty-seven low grade OECs (35 associated with endometriosis) were
      stained immunohistochemically for beta-catenin, cyclin D1, BAF250a, PTEN, p53,
      WT1 and the mismatch repair (MMR) proteins MLH1, PMS2, MSH2 and MSH6. The results
      were correlated with KRAS mutation analysis and the presence of concurrent
      endometriosis. RESULTS: Abnormal beta-catenin, cyclin D1, BAF250a, PTEN, p53 and
      MMR protein expression was identified in 61.2%, 50.7%, 19.4%, 23.9%, 9.0%, and
      6.0% of cases, respectively; these changes were equally common in endometriosis
      positive and negative tumours. WT1 expression was restricted to endometriosis
      negative EOC (8/32, 25%) and four WT1 positive cases showed sertoliform/spindle
      cell histological patterns. Abnormal beta-catenin expression correlated with
      cyclin D1 overexpression but was inversely related to KRAS mutation.
      Immunophenotypic abnormalities were present in four of 17 histologically benign
      endometriotic lesions. CONCLUSIONS: Most immunophenotypic alterations were
      equally common in endometriosis associated and independent OECs but only the
      latter were associated with abnormal WT1 expression. The inverse relationship
      between abnormal beta-catenin expression and KRAS mutation merits further study.
      Histologically benign endometriotic epithelium may show immunophenotypic
      abnormalities similar to those present in associated carcinomas.

PMID- 24018809
TI  - Assessment of the BD GeneOhm MRSA ACP assay using combined swabs for the
      detection of methicillin resistant Staphylococcus aureus (MRSA) colonisation.

PMID- 24018810
TI  - IgG4 related disease of the thyroglossal duct.

PMID- 24018811
TI  - Intracortical chondroma of the humerus in a child.

PMID- 24018812
TI  - Changing the way referring general practitioners request urinary albumin studies.

PMID- 24018813
TI  - Interobserver variability in the diagnosis of circumscribed sebaceous neoplasms
      of the skin.
AB  - AIMS: Separation of sebaceous adenoma, sebaceoma and well differentiated
      sebaceous carcinoma is a clinically important distinction which relies on a
      number of subjective criteria. In routine practice we had noted significant
      interobserver variability in the classification of these lesions. This study
      sought to determine the degree of interobserver variability between general
      surgical pathologists and dermatopathologists in the diagnosis of well
      differentiated cutaneous sebaceous neoplasms. METHODS: We circulated 61 examples
      of well circumscribed cutaneous sebaceous neoplasms to nine pathologists,
      including dermatopathologists and general surgical pathologists who were asked to
      submit a diagnosis for each case. Fleiss' kappa statistic was used for assessment
      of interobserver agreement. RESULTS: We found that only seven cases (11%) had
      consensus agreement across all nine pathologists. Many cases had multiple
      diagnoses suggested, with three or more submitted diagnoses in 26 cases (43%),
      while 38 cases (62%) were diagnosed as sebaceous carcinoma by at least one
      pathologist. There was marked variability amongst the individual pathologists in
      the proportion of cases diagnosed as carcinoma, ranging from 5% to 57% of cases.
      Fleiss' kappa statistic for all pathologists across all diagnostic categories was
      0.44, amounting to only fair to moderate agreement. CONCLUSIONS: These data
      indicate that there is substantial interobserver variability in the diagnosis of
      well circumscribed sebaceous neoplasms. This was seen in both the separation of
      benign and malignant lesions, as well as in the classification of the benign
      entities. This interobserver variability is likely to have significant clinical
      implications in terms of potential for over- or under-treatment, as well as in
      selection of cases for mismatch repair protein evaluation.

PMID- 24018814
TI  - Acquired carbapenemases in Enterobactericeae in Singapore, 1996-2012.
AB  - AIMS: To characterise carbapenemase-producing Enterobacteriaceae (CRE) isolated
      in Singapore. METHODS: Carbapenemase genes and their flanking regions were
      amplified and sequenced by PCR. Isolates were typed by pulsed-field gel
      electrophoresis and multi-locus sequence typing. Plasmids bearing carbapenemase
      genes were sized by S1 nuclease digestion, Southern blotting, and DNA
      hybridisation with appropriate probes. Transfer of these plasmids was attempted
      by conjugation and transformation. Successfully transferred plasmids were
      characterised by polymerase chain reaction (PCR) replicon typing and restriction
      digestion. RESULTS: Isolates of Klebsiella pneumoniae, Escherichia coli,
      Enterobacter cloacae and Citrobacter species carried a variety of carbapenemase
      genes including blaIMP-1, blaIMP-4, blaNDM-1, blaNDM-7, blaOXA-181, blaOXA-48 and
      blaKPC-2. Apart from K. pneumoniae with blaOXA-181, and some K. pneumoniae with
      blaNDM-1, the other isolates were not clonal. However there appears to be some
      spread of plasmids with blaIMP-1, blaNDM-1,blaKPC-2, and blaOXA-48. CONCLUSIONS:
      The number of isolates of CRE has increased in Singapore, especially since 2010.
      There is a diversity of carbapenemase types that reflects the geographical
      proximity of other countries with CRE.

PMID- 24018815
TI  - Multiplex PCR targeting slpA: a rapid screening method to predict common
      Clostridium difficile ribotypes among fluoroquinolone resistant clinical strains.
AB  - AIMS: Based on the relationship between Clostridium difficile surface layer
      protein A (slpA) sequence types (STs) and PCR-ribotypes (RTs), a multiplex
      polymerase chain reaction (mPCR) assay was developed to rapidly confirm C.
      difficile toxigenicity and, simultaneously, to identify any of five slpA STs, gr,
      hr, fr, gc8 and 078, that usually correspond with globally distributed RTs, 001,
      014, 017, 027 and 078, respectively. METHODS: The mPCR, containing five slpA type
      specific primers, was developed using 46 well-characterised C. difficile
      reference strains, representing 11 slpA STs, and validated by testing 90C.
      difficile clinical isolates. RESULTS: The slpA mPCR correctly identified the five
      slpA STs without cross-reactions. A much higher proportion of moxifloxacin
      resistant (32/39; 82%) than susceptible (12/51; 24%) clinical isolates were slpA
      typeable (chi=30.3, p<0.0001), even when RT027 isolates were excluded [10/17
      (59%) versus 12/51 (24%); chi=7.3, p=0.0071<0.01]. slpA mPCR correctly predicted
      the RTs of all 39 isolates that belonged to the five targeted RTs. CONCLUSION:
      slpA mPCR is simple, rapid and inexpensive. It can provisionally identify five
      globally significant, highly transmissible RTs, particularly among moxifloxacin
      resistant C. difficile isolates, and could be easily modified to include a
      broader range of slpA sequence types, based on local requirements.

PMID- 24018816
TI  - The International Association for the Study of Lung Cancer/American Thoracic
      Society/European Respiratory Society grading system has limited prognostic
      significance in advanced resected pulmonary adenocarcinoma.
AB  - INTRODUCTION: The International Association for the Study of Lung Cancer, the
      American Thoracic Society and the European Respiratory Society (IASLC/ATS/ERS)
      system which subclassifies lung adenocarcinoma into five distinct types has been
      widely adopted. We assessed the prognostic value of subclassifying adenocarcinoma
      in this way in consecutive patients undergoing surgery. METHODS: All patients at
      our institution undergoing surgery for lung carcinoma between 2000 and 2010 were
      identified. The original pathology slides were independently reviewed and
      reclassified according to the 2011 IASLC/ATS/ERS grading and the American Joint
      Committee on Cancer (AJCC) 7 edition 2009 staging systems. RESULTS: We identified
      270 patients including 152 with adenocarcinoma histology with long-term follow
      up. Using the Kaplan-Meier method, the calculated 5 year survival for each of the
      adenocarcinoma categories were papillary-predominant 80%, lepidic-predominant
      71%, micropapillary-predominant 55%, acinar-predominant 43%, solid-predominant
      39% and invasive mucinous adenocarcinoma 38%. The AJCC stage was a very strong
      predictor of survival (p<0.001). The IASLC/ATS/ERS subclassification of
      adenocarcinoma demonstrated a trend as a prognostic marker but failed to reach
      statistical significance in univariate or multivariate analysis. CONCLUSION:
      Although the IASLC/ATS/ERS classification has been validated by several studies
      in stage I tumours, further studies of larger cohorts will be required to show
      prognostic value in unselected lung carcinoma undergoing surgery with curative
      intent.

PMID- 24018817
TI  - Thyroid-like papillary adenocarcinoma of the nasopharynx with focal thyroglobulin
      expression.

PMID- 24018818
TI  - BAP1 expression in cutaneous melanoma: a pilot study.

PMID- 24018819
TI  - Genital melanocytic naevus and lichen sclerosus.

PMID- 24018820
TI  - Unravelling the prognostic effect of IKZF1 deletions and IGH@-CRLF2 in adult
      acute lymphoblastic leukaemia.

PMID- 24018821
TI  - Increase of exostosin 1 in plasma as a potential biomarker for opisthorchiasis
      associated cholangiocarcinoma.
AB  - A proteomic-based approach was used to search for potential markers in the plasma
      of hamsters in which cholangiocarcinoma (CCA) was induced by Opisthorchis
      viverrini infection and N-nitrosodimethylamine treatment. The plasma proteins of
      CCA-induced hamsters were resolved by 1-D PAGE, digested by trypsin, and analyzed
      by LC-MS/MS. From the criteria of protein ID scores >15 and an overexpression of
      at least three times across all time points, 37 proteins were selected. These
      overexpressed proteins largely consisted of signal transduction, structural,
      transport, and transcriptional proteins in the order. Among the most frequently
      upregulated proteins, exostosin 1 (EXT1) was selected for further validation. By
      western blot analysis, the EXT1 expression level in the plasma of hamster CCA was
      significantly higher than that of controls at 1 month and thereafter.
      Immunohistochemistry revealed that EXT1 was expressed at vascular walls and
      fibroblasts at 21 days (before tumor onset) and at 2 months (early CCA)
      posttreatment. Its expression was also observed in bile duct cancer cells during
      tumor progression at 6 months posttreatment. In the human CCA tissue microarray,
      EXT1 immunoreactivity was found not only in vascular walls and fibroblasts but
      also in bile duct cancer cells and was positive in 89.7 % (61/68) of the cases.
      By ELISA and immunoblotting, plasma EXT1 level was significantly higher in human
      CCA compared to healthy controls. In conclusion, these results suggest that
      increased expression of EXT1 level in the plasma might be involved in CCA genesis
      and might be a potential biomarker of CCA.

PMID- 24018822
TI  - Diagnostic relevance of plasma DNA and DNA integrity for breast cancer.
AB  - Levels of ALU 115, ALU 247, DNA integrity ([1, 2]) and of the tumour markers CA
      15-3 and CEA were analysed in the blood of 152 patients. Plasma levels of ALU 115
      and ALU 247 were significantly higher in patients with locally confined (LBC; N =
      65), metastatic breast cancer (MBC; N = 47), and benign diseases (N = 12) than in
      healthy controls (p < 0.001 for all comparisons). DNA integrity, CEA, and CA 15-3
      were significantly higher in MBC than in benign controls and LBC but could not
      identify LBCs. The best discrimination of LBC from healthy controls was achieved
      by ALU 115 and ALU 247 (AUC 95.4 and 95.5 %) and of MBC from all control groups
      by CA 15-3 and CEA (AUC 83.2 and 79.1 %). Plasma DNA is valuable for the
      detection of LBC, while established tumour markers are most informative in MBC.

PMID- 24018823
TI  - High cofilin-1 levels correlate with cisplatin resistance in lung
      adenocarcinomas.
AB  - High cofilin-1 levels have been shown to be an accurate prognostic biomarker in
      non-small cell lung cancer (NSCLC) and a predictive factor in drug resistance.
      Herein we explore the role of cofilin-1 in cis-diamminedichloroplatinum(II)
      (cisplatin) resistance. We evaluated cofilin-1 levels in intrinsically cisplatin
      resistant A549 (ICR-A549) cells and determined the cisplatin toxicity in A549
      cells transiently transfected and overexpressing CFL1 plasmid. Moreover,
      expression levels (activity) of the CFL1 gene network were analyzed in a
      cisplatin-resistant human lung adenocarcinoma cell panel. ICR-A549 cells,
      selected by challenging parental cells with 10-fold drug GI50 value, presented a
      sixfold increase in cisplatin GI50 value and an increased cofilin-1 immunocontent
      (P < 0.01). In addition, cells transfected with cofilin-1 became more resistant
      to cisplatin (P < 0.01). High activity of the CFL1 gene network was found in a
      cisplatin-resistant adenocarcinoma cell panel (P < 0.01). In vitro evidences
      suggest that cofilin-1 is a biological predictor of cisplatin resistance,
      supporting new treatment initiatives based on cofilin-1 levels to guide
      chemotherapeutic interventions in NSCLC patients.

PMID- 24018824
TI  - Synergistic co-delivery of membrane-disrupting polymers with commercial
      antibiotics against highly opportunistic bacteria.
AB  - A series of vitamin E-containing biodegradable antimicrobial cationic
      polycarbonates is designed and synthesized via controlled organocatalytic ring
      opening polymerization. The incorporation of vitamin E significantly enhances
      antimicrobial activity. These polymers demonstrate broad-spectrum antimicrobial
      activity against various microbes, e.g., S. aureus (Gram-positive), E-coli (Gram
      negative) and C. albicans (fungi). More importantly, the co-delivery of such
      polymers with selected antibiotics (e.g., doxycycline) shows high synergism
      towards difficult-to-kill bacteria P. aeruginosa. These findings suggest that
      these vitamin E-functionalized polycarbonates are potentially useful
      antimicrobial agents against challenging bacterial/fungal infections. 

PMID- 24018826
TI  - Zygomycotic mediastinal lymphadenitis in beef cattle with ruminal tympany.
AB  - A 9-month-old steer was autopsied due to recurrent ruminal tympany. A macroscopic
      examination found an enlarged caudal mediastinal lymph node, and a section of the
      lymph node revealed necrosis with marked calcification, similar to tuberculous
      lymphadenitis. Histopathologically, the lesion consisted of multiple coagulative
      necrotic foci and fibrosis with macrophage, lymphocyte, eosinophil and
      multinucleated giant cell infiltration. Non-uniform width hyphae were detected in
      the necrotic area and within the cytoplasm of the multinucleated giant cells, and
      they were found to be anti-Rhizopus arrhizus antibody positive in an
      immunohistochemical examination. Therefore, the steer was diagnosed with necrotic
      caudal mediastinal lymphadenitis due to zygomycetes infection, and inhibition of
      eructation by the enlarged lymph node was the likely cause of the ruminal
      tympany. 

PMID- 24018827
TI  - Contamination of poultry products with Listeria monocytogenes at poultry
      processing plants.
AB  - This study aimed to confirm that poultry products packed at poultry processing
      plants have already been contaminated with Listeria monocytogenes and that
      poultry products contaminated with L. monocytogenes are derived from broiler
      flocks infected with L. monocytogenes. L. monocytogenes was isolated from 16.8%
      (58/345) of chicken breast products and 2.3% (8/345) of chicken liver products.
      In contrast, L. monocytogenes was isolated from the pooled cecal content sample
      from only 1 (4%) of 25 flocks and was never isolated from any pooled dropping
      samples collected from 25 farms. The results of our study indicate that cecal
      content does not seem to be an important source of L. monocytogenes in poultry
      products. 

PMID- 24018828
TI  - Development of a hybrid physiologically based pharmacokinetic model with drug
      specific scaling factors in rat to improve prediction of human pharmacokinetics.
AB  - Accurate prediction of pharmacokinetics (PK) in humans has been a vital part of
      drug discovery. The aims of this study are to verify the usefulness of scaling
      factors for clearance (CL) and apparent volume of distribution at the steady
      state (Vss ) estimated from the difference between observed and predicted PK
      profiles in rats for human PK prediction, and to develop a novel hybrid
      physiologically based pharmacokinetic (PBPK) model with the two scaling factors.
      The human prediction accuracies for CL with in vitro-in vivo extrapolation and
      Vss with a tissue composition model were improved by using rat-scaling factors.
      This improvement was explainable by data that the scaling factors for CL and Vss
      in rats were correlated with those in humans. The predictability of plasma
      concentration-time profiles by the hybrid PBPK model incorporating two scaling
      factors was compared mainly with that by the conventional PBPK model. The hybrid
      PBPK model yielded higher prediction accuracy for plasma concentrations than the
      conventional method. Furthermore, we proposed a tiered approach using the three
      prediction methods, including the hybrid Dedrick approach, that were previously
      reported (Sayama H, Komura H, Kogayu M. 2013. Drug Metab Dispos 41:498-507),
      taking the available information in the individual stages of drug discovery and
      development into consideration.

PMID- 24018829
TI  - Effect of spine hardware on small spinal stereotactic radiosurgery dosimetry.
AB  - Monte Carlo (MC) modeling of a 6 MV photon beam was used to study the dose
      perturbation from a titanium rod 5 mm in diameter in various small fields range
      from 2 * 2 to 5 * 5 cm(2). The results showed that the rod increased the dose to
      water by ~6% at the water-rod interface because of electron backscattering and
      decreased the dose by ~7% in the shadow of the rod because of photon attenuation.
      The Pinnacle(3) treatment planning system calculations matched the MC results at
      the depths more than 1 cm past the rod when the correct titanium density of 4.5 g
      cm(-3) was used, but significantly underestimated the backscattering dose at the
      water-rod interface. A CT-density table with a top density of 1.82 g cm(-3)
      (cortical bone) is a practical way to reduce the dosimetric error from the
      artifacts by preventing high density assignment to them, but can underestimates
      the attenuation by the titanium rod by 6%. However, when multi-beam with
      intensity modulation is used in actual patient spinal stereotactic radiosurgery
      treatment, the dosimetric effect of assigning 4.5 instead of 1.82 g cm(-3) to
      titanium implants is complicated. It ranged from minimal effect to 2% dose
      difference affecting 15% target volume in the study. When hardware is in the beam
      path, density override to the titanium hardware is recommended. 

PMID- 24018830
TI  - QTc prolongation in methadone maintenance--the role of HCV infection.
AB  - OBJECTIVES: Several studies have reported prolonged QTc intervals in patients
      under methadone maintenance treatment, including development of torsade-de
      pointes arrhythmia and death. It is still not clear why some patients develop
      critical QTc extensions while others do not. METHODS: ECG findings in a
      convenience sample of 210 methadone-maintained heroin-dependent patients, taking
      HCV-infection status and methadone dosage into account simultaneously by means of
      a multiple linear regression model with QTc-interval as the dependent variable.
      RESULTS: Prolonged QTc-time is associated with hepatitis C infections (p = 0.005)
      and higher doses of racemic methadone (p = 0.012). CONCLUSION: Infection with
      hepatitis C increases the likelihood of critical QTc prolongation in patients in
      methadone maintenance treatment.

PMID- 24018831
TI  - Biogenic growth of alloys and core-shell nanostructures using urease as a
      nanoreactor at ambient conditions.
AB  - Biomineralization is an extremely efficient biologically guided process towards
      the advancement of nano-bio integrated materials. As a prime module of the
      natural world, enzymes are expected to play a major role in biogenic growth of
      inorganic nanostructures. Although there have been developments in designing
      enzyme-responsive nanoparticle systems or generation of inorganic nanostructures
      in an enzyme-stimulated environment, reports regarding action of enzymes as
      reducing agents themselves for the growth of inorganic nanoparticles still
      remains elusive. Here we present a mechanistic investigation towards the
      synthesis of metal and metallic alloy nanoparticles using a commonly investigated
      enzyme, Jack bean urease (JBU), as a reducing as well as stabilizing agent under
      physiological conditions. The catalytic functionality of urease was taken
      advantage of towards the development of metal-ZnO core-shell nanocomposites,
      making urease an ideal bionanoreactor for synthesizing higher order
      nanostructures such as alloys and core- shell under ambient conditions. 

PMID- 24018832
TI  - Bone scan, MRI, and FDG PET/CT findings in composite hemangioendothelioma of the
      manubrium sterni.
AB  - Composite hemangioendothelioma (HE) is a recently described rare vascular
      neoplasm of low-grade malignancy. A 56-year-old man presented with sternum pain
      for 2 years. Bone scan showed a hot spot in the manubrium sterni. This lesion
      showed high signal intensity on T2-weighted MR images and high vascularity on
      enhanced T1-weighted MR images. F-FDG PET/CT showed increased FDG uptake of this
      osteolytic lesion with SUVmax of 5.9. Malignant tumor was suspected. The patient
      underwent resection of the lesion. Composite HE was confirmed by pathology. 

PMID- 24018834
TI  - At the ionic liquid|metal interface: structure formation and temperature
      dependent behavior of an ionic liquid adlayer on Au(111).
AB  - The growth, structure formation and thermal disordering of (sub-)monolayer films
      of 1-butyl-1-methylpyrrolidinium-bis(trifluoromethylsulfonyl)imide [BMP][TFSA]
      grown under ultrahigh vacuum (UHV) conditions on Au(111) have been investigated
      using scanning tunneling microscopy (STM) and angle resolved X-ray photoelectron
      spectroscopy (ARXPS) under UHV conditions at temperatures between 100 and 298 K.
      At room temperature, two-dimensional film growth occurs up to one monolayer
      coverage, with both cations and anions in direct contact with the gold substrate,
      as shown by ARXPS, and STM images reveal a 2D liquid state of the adlayer. At
      lower temperatures, motion is frozen and a disordered 2D glass state as well as a
      2D crystalline phase with long-range order are formed. The structure of the 2D
      crystalline phase is influenced by the underlying Au(111) reconstruction pattern.
      Annealing experiments reveal that the 2D crystalline phase is thermally more
      stable against melting than the 2D glass state, and that the stability is
      strongly affected by the adsorbate coverage. 

PMID- 24018833
TI  - Multiwell stiffness assay for the study of cell responsiveness to cytotoxic
      drugs.
AB  - It is now well understood that the cell microenvironment, including the
      surrounding matrix, profoundly affects cell fate. This is especially true for
      solid tumors where, for example, matrix stiffness is believed to be an important
      factor in tumorogenesis. Our hypothesis is that since matrix stiffness affects
      cell fate, it may also be important in drug resistance. To test this hypothesis,
      we designed and built a multiwell polyacrylamide (PA) gel-based stiffness assay,
      in which the gels were coated with collagen in order to facilitate cell
      attachment and proliferation. This PA-based assay was used to examine the effect
      of stiffness on cultured cell responsiveness to cytotoxic drugs. In particular,
      we tested multiple cancer cell lines and their susceptibility to paclitaxel, a
      microtubule-targeting agent. By assessing cell proliferation, morphology, and the
      IC50 of the drug, we were able to establish that the stiffness affects
      responsiveness to cytotoxic drugs in a cell-dependent manner.

PMID- 24018835
TI  - Using Exenatide Twice Daily or Insulin in Clinical Practice: Results from CHOICE.
AB  - INTRODUCTION: CHOICE (CHanges to treatment and Outcomes in patients with type 2
      diabetes initiating InjeCtablE therapy; NCT00635492) assessed, as its primary
      objective, the time to a 'significant treatment change' (defined within this
      paper) after patients with type 2 diabetes mellitus initiated their first
      injectable, glucose-lowering therapy [exenatide twice daily (BID) or insulin] in
      clinical practice in six European countries and evaluated outcomes during the
      study. METHODS: CHOICE was a 24-month, prospective, noninterventional
      observational study. Patients were invited to participate in CHOICE only after
      their treating physician had made the clinical decision to initiate first
      injectable therapy with either exenatide BID or insulin. Clinical data were
      collected at initiation of first injectable therapy and after approximately 3, 6,
      12, 18, and 24 months. RESULTS: A total of 2,515 patients were recruited; 1,114
      patients in the exenatide BID cohort and 1,274 patients in the insulin cohort
      were eligible for the 24-month analysis. During the study, 42.2% and 36.0% of
      patients from each cohort, respectively, had a significant treatment change. By
      24 months, improved mean glycated hemoglobin (p < 0.001 for both cohorts) and
      reduced severity of several cardiovascular risk factors were observed in both
      cohorts; additionally, mean weight was reduced in the exenatide BID cohort (p <
      0.001) and increased in the insulin cohort (p < 0.001). Hypoglycemia was reported
      by 18.4% of the exenatide BID cohort and 36.8% of the insulin cohort; 25.9% of
      the exenatide BID cohort and 10.0% of the insulin cohort had met the secondary
      endpoint of glycated hemoglobin <7.0%, no weight gain, and no hypoglycemia.
      CONCLUSION: CHOICE provided data on exenatide BID and insulin usage patterns and
      24-month outcomes in clinical practice. On average, improved glycemic control and
      reduced severity of cardiovascular risk factors were observed in both cohorts,
      and those in the exenatide BID cohort also had mean weight loss.

PMID- 24018836
TI  - Enzyme confined in silica-based nanocages for biocatalysis in a Pickering
      emulsion.
AB  - The encapsulation of lipase into the nanocages of FDU-12 and the amphiphilic
      modification of the surfaces of FDU-12 can concurrently be accomplished via a
      facile silylation method. The obtained lipase-loaded FDU-12 particles featuring
      superior biocatalytic activity and negligible enzyme leaching can serve as
      efficient stabilizers for a Pickering emulsion to enhance the performance of
      biphasic enzymatic reactions. 

PMID- 24018837
TI  - An evaluation of microbial and chemical contamination sources related to the
      deterioration of tap water quality in the household water supply system.
AB  - The predominant microorganisms in samples taken from shower heads in residences
      in the Korean city "N" were Stenotrophomonas maltophilia, Sphingomonas
      paucimobilis, Acidovorax temperans, and Microbacterium lacticum. Legionella was
      not detected in this case. The volatile organic compounds (VOCs) vinylacetate, NN
      DMA, cis-1,2-dichloroethylene, epichlorohydrin, and styrene were measured in five
      types of plastic pipes: PVC, PB, PP, PE, and cPVC. The rate of multiplication of
      the heterotrophic plate count (HPC) attached on the copper pipe in contact with
      hot tap water was higher than the rate for the copper pipe in contact with cold
      tap water. Biofilm accumulation on stainless steel pipes with added acetate (3
      mg/L) was 2.56 times higher than the non-supplemented condition. Therefore, the
      growth of HPC in the pipe system was affected by the type and availability of
      nutrients and depended on variables such as heating during the hot water supply. 

PMID- 24018838
TI  - Mapping disease at an approximated individual level using aggregate data: a case
      study of mapping New Hampshire birth defects.
AB  - BACKGROUND: Limited by data availability, most disease maps in the literature are
      for relatively large and subjectively-defined areal units, which are subject to
      problems associated with polygon maps. High resolution maps based on objective
      spatial units are needed to more precisely detect associations between disease
      and environmental factors. METHOD: We propose to use a Restricted and Controlled
      Monte Carlo (RCMC) process to disaggregate polygon-level location data to achieve
      mapping aggregate data at an approximated individual level. RCMC assigns a random
      point location to a polygon-level location, in which the randomization is
      restricted by the polygon and controlled by the background (e.g., population at
      risk). RCMC allows analytical processes designed for individual data to be
      applied, and generates high-resolution raster maps. RESULTS: We applied RCMC to
      the town-level birth defect data for New Hampshire and generated raster maps at
      the resolution of 100 m. Besides the map of significance of birth defect risk
      represented by p-value, the output also includes a map of spatial uncertainty and
      a map of hot spots. CONCLUSIONS: RCMC is an effective method to disaggregate
      aggregate data. An RCMC-based disease mapping maximizes the use of available
      spatial information, and explicitly estimates the spatial uncertainty resulting
      from aggregation.

PMID- 24018839
TI  - Racial differences in survival among hemodialysis patients after coronary artery
      bypass grafting.
AB  - The aim of this study was to examine racial differences in long-term survival
      among hemodialysis patients after coronary artery bypass grafting (CABG). To our
      knowledge this has not been previously addressed in the literature. Black and
      white hemodialysis patients undergoing first-time, isolated CABG procedures
      between 1992 and 2011 were compared. Survival probabilities were computed using
      the Kaplan-Meier product-limit method and stratified by race. Hazard ratios (HR)
      and 95% confidence intervals (CI) were computed using a Cox regression model. A
      total of 207 (2%) patients were on hemodialysis at the time of CABG. White (n =
      80) hemodialysis patients had significantly decreased 5-year survival compared
      with black (n = 127) patients (adjusted HR = 1.9, 95% CI = 1.2-2.8). Our finding
      provides useful outcome information for surgeons, primary care providers, and
      their patients. 

PMID- 24018840
TI  - NEMA NU 4-2008 validation and applications of the PET-SORTEO Monte Carlo
      simulations platform for the geometry of the Inveon PET preclinical scanner.
AB  - Monte Carlo-based simulation of positron emission tomography (PET) data plays a
      key role in the design and optimization of data correction and processing
      methods. Our first aim was to adapt and configure the PET-SORTEO Monte Carlo
      simulation program for the geometry of the widely distributed Inveon PET
      preclinical scanner manufactured by Siemens Preclinical Solutions. The validation
      was carried out against actual measurements performed on the Inveon PET scanner
      at the Australian Nuclear Science and Technology Organisation in Australia and at
      the Brain & Mind Research Institute and by strictly following the NEMA NU 4-2008
      standard. The comparison of simulated and experimental performance measurements
      included spatial resolution, sensitivity, scatter fraction and count rates, image
      quality and Derenzo phantom studies. Results showed that PET-SORTEO reliably
      reproduces the performances of this Inveon preclinical system. In addition,
      imaging studies showed that the PET-SORTEO simulation program provides raw data
      for the Inveon scanner that can be fully corrected and reconstructed using the
      same programs as for the actual data. All correction techniques (attenuation,
      scatter, randoms, dead-time, and normalization) can be applied on the simulated
      data leading to fully quantitative reconstructed images. In the second part of
      the study, we demonstrated its ability to generate fast and realistic biological
      studies. PET-SORTEO is a workable and reliable tool that can be used, in a
      classical way, to validate and/or optimize a single PET data processing step such
      as a reconstruction method. However, we demonstrated that by combining a
      realistic simulated biological study ([(11)C]Raclopride here) involving different
      condition groups, simulation allows one also to assess and optimize the data
      correction, reconstruction and data processing line flow as a whole, specifically
      for each biological study, which is our ultimate intent. 

PMID- 24018841
TI  - Anti-atherogenic effects of a new thienylacylhydrazone derivative, LASSBio-788,
      in rats fed a hypercholesterolemic diet.
AB  - The compound LASSBio-788 (N-Allyl (2-thienylidene) 3,4
      methylenedioxybenzoylhydrazine) is a thienylacylhydrazone derivative shown to
      have antiplatelet, vasodilatory, and anti-inflammatory properties in vitro. We
      hypothesize that LASSBio-788 may exert beneficial effects on atherosclerosis.
      Male wistar rats were divided into 4 groups: Control group received standard rat
      chow, hypercholesterolemic group (HC) and HC+788 (compound LASSBio-788 group)
      received hypercholesterolemic diet for 45 days. HC+788 group received compound
      LASSBio-788 (100 MUmol/kg) once daily in the last 15 days. LASSBio-788 reduced
      the levels of total cholesterol (109.1 +/- 4.3 vs. 361.0 +/- 12.8 mg/dl),
      triglycerides (66.1 +/- 1.1 vs. 186.9 +/- 17.7 mg/dl), LDLc (63.2 +/- 6.1 vs.
      330.9 +/- 9.7 mg/dl), VLDLc (9.8 +/- 1.1 vs. 45.0 +/- 4.6 mg/dl) and
      malondialdehyde (4.8 +/- 0.3 vs. 9.4 +/- 0.5 nmol/ml) compared to the HC group.
      LASSBio-788 presented antiplatelet properties and decreased inflammatory markers
      levels. LASSBio-788 promoted a decrease in contractile response to phenylephrine
      and an improvement in endothelium-dependent vasorelaxant response by increasing
      two-fold the expression of nitric oxide synthase (eNOS). Our results suggest that
      the compound LASSBio-788 represents a new multi-targeted drug candidate for the
      treatment of atherosclerosis. 

PMID- 24018843
TI  - Encapsulated monoclinic sulfur for stable cycling of li-s rechargeable batteries.
AB  - Monoclinic S8 , an uncommon allotrope of sulfur at room temperature, can be
      formed when common orthorhombic S8 is heat-treated under enclosed environments in
      nanometer dimensions. Monoclinic S8 prevents the formation of soluble
      polysulfides during battery operation, resulting in unprecedented cycling
      performance over 1000 cycles under the highest sulfur content to date. 

PMID- 24018842
TI  - Oxidative stress improves coronary endothelial function through activation of the
      pro-survival kinase AMPK.
AB  - Age-associated decline in cardiovascular function is believed to occur from the
      deleterious effects of reactive oxygen species (ROS). However, failure of recent
      clinical trials using antioxidants in patients with cardiovascular disease, and
      the recent findings showing paradoxical role for NADPH oxidase-derived ROS in
      endothelial function challenge this long-held notion against ROS. Here, we
      examine the effects of endothelium-specific conditional increase in ROS on
      coronary endothelial function. We have generated a novel binary (Tet-ON/OFF)
      conditional transgenic mouse (Tet-Nox2:VE-Cad-tTA) that induces endothelial cell
      (EC)-specific overexpression of Nox2/gp91 (NADPH oxidase) and 1.8?0.42-fold
      increase in EC-ROS upon tetracycline withdrawal (Tet-OFF). We examined ROS
      effects on EC signaling and function. First, we demonstrate that endothelium
      dependent coronary vasodilation was significantly improved in Tet-OFF Nox2
      compared to Tet-ON (control) littermates. Using EC isolated from mouse heart, we
      show that endogenous ROS increased eNOS activation and nitric oxide (NO)
      synthesis through activation of the survival kinase AMPK. Coronary vasodilation
      in Tet-OFF Nox2 animals was CaMKK?-AMPK-dependent. Finally, we demonstrate that
      AMPK activation induced autophagy and thus, protected ECs from oxidant-induced
      cell death. Together, these findings suggest that increased ROS levels, often
      associated with cardiovascular conditions in advanced age, play a protective role
      in endothelial homeostasis by inducing AMPK-eNOS axis. 

PMID- 24018844
TI  - Randomized trials analyzed as observational studies.

PMID- 24018846
TI  - Antibacterial, antiurease, and antioxidant activities of some arylidene
      barbiturates.
AB  - Some series of arylidene barbiturates and thiobarbiturates were evaluated for
      their antibacterial, antioxidant, and urease inhibition activities. The arylidene
      barbiturates and thiobarbiturates were tested for antimicrobial activity using
      the agar well diffusion technique against 13 bacteria. The synthesized compounds
      (1a-g) were screened for antiurease and antioxidant activities. The results
      showed that the synthesized compounds (1a-g) had effective antiurease,
      antioxidant, and antibacterial activities. 

PMID- 24018847
TI  - Effect of the addition of zero valent iron (Fe(0)) on the batch biological
      sulphate reduction using grass cellulose as carbon source.
AB  - Mineral mining generates acidic, saline, metal-rich mine waters, often referred
      to as acid mine drainage (AMD). Treatment of AMD and recovering saleable products
      during the treatment process are a necessity since water is, especially in South
      Africa, a scarce commodity. The aim of the study presented here was to
      investigate the effect of zero valent iron (Fe(0)) on the biological removal of
      sulphate from AMD in batch reactors. The performance of the reactors was assessed
      by means of sulphate reduction, chemical oxygen demand (COD), volatile fatty acid
      (VFA) utilisation and volatile suspended solids (VSS) concentration. To this end,
      three batch reactors, A, B and C (volume 2.5 L), were operated similarly with the
      exception of the addition of grass cuttings and iron filings. Reactors A and B
      received twice as much grass (100 g) as C (50 g). Reactor A received no iron
      filings to act as a control, while reactors B and C received 50-g iron filings
      for the experimental duration. The results showed that Fe(0) appears to provide
      sustained sulphate removal when sufficient grass substrate is available. In
      reactors A and C, sulphate removal efficiency was higher when the COD
      concentration was lower due to utilisation. In reactor B, sulphate removal
      efficiency was accompanied by an accumulation of COD as hydrogen (H2) provided by
      the Fe(0) was utilised for sulphate reduction. Furthermore, these results showed
      the potential of Fe(0) to enhance the participation of microorganisms in sulphate
      reduction.

PMID- 24018848
TI  - Cranberry flowering times and climate change in southern Massachusetts.
AB  - Plants in wild and agricultural settings are being affected by the warmer
      temperatures associated with climate change. Here we examine the degree to which
      the iconic New England cranberry, Vaccinium macrocarpon, is exhibiting signs of
      altered flowering phenology. Using contemporary records from commercial cranberry
      bogs in southeastern Massachusetts in the United States, we found that cranberry
      plants are responsive to temperature. Flowering is approximately 2 days earlier
      for each 1  degrees C increase in May temperature. We also investigated the
      relationship between cranberry flowering and flight dates of the bog copper,
      Lycaena epixanthe-a butterfly dependent upon cranberry plants in its larval
      stage. Cranberry flowering and bog copper emergence were found to be changing
      disproportionately over time, suggesting a potential ecological mismatch. The
      pattern of advanced cranberry flowering over time coupled with increased
      temperature has implications not only for the relationship between cranberry
      plants and their insect associates but also for agricultural crops in general and
      for the commercial cranberry industry.

PMID- 24018849
TI  - The effect of solar-geomagnetic activity during and after admission on survival
      in patients with acute coronary syndromes.
AB  - A number of studies have established the effects of solar-geomagnetic activity on
      the human cardio-vascular system. It is plausible that the heliophysical
      conditions existing during and after hospital admission may affect survival in
      patients with acute coronary syndromes (ACS). We analyzed data from 1,413 ACS
      patients who were admitted to the Hospital of Kaunas University of Medicine,
      Lithuania, and who survived for more than 4 days. We evaluated the associations
      between active-stormy geomagnetic activity (GMA), solar proton events (SPE), and
      solar flares (SF) that occurred 0-3 days before and after admission, and 2-year
      survival, based on Cox's proportional-hazards model, controlling for clinical
      data. After adjustment for clinical variables, active-stormy GMA on the 2nd day
      after admission was associated with an increased (by 1.58 times) hazard ratio
      (HR) of cardiovascular death (HR=1.58, 95 % CI 1.07-2.32). For women, geomagnetic
      storm (GS) 2 days after SPE occurred 1 day after admission increased the HR by
      3.91 times (HR=3.91, 95 % CI 1.31-11.7); active-stormy GMA during the 2nd-3rd day
      after admission increased the HR by over 2.5 times (HR=2.66, 95 % CI 1.40-5.03).
      In patients aged over 70 years, GS occurring 1 day before or 2 days after
      admission, increased the HR by 2.5 times, compared to quiet days; GS in
      conjunction with SF on the previous day, nearly tripled the HR (HR=3.08, 95 % CI
      1.32-7.20). These findings suggest that the heliophysical conditions before or
      after the admission affect the hazard ratio of lethal outcome; adjusting for
      clinical variables, these effects were stronger for women and older patients.

PMID- 24018850
TI  - The expression of hypoxia-inducible factor-1alpha and its clinical significance
      in lung cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Hypoxia-inducible factor-1alpha (HIF-1alpha) plays an important role
      in tumour progression and metastasis through activation of many target genes that
      are especially involved in pivotal aspects of cancer biology. However, the
      prognostic role of HIF-1alpha has been controversial in primary patients with
      lung cancer. This meta-analysis was performed to systematically evaluate whether
      HIF-1alpha expression is associated with the clinical outcomes in lung cancer
      patients. METHODS: We retrieved relevant articles from Cochrane library, PubMed,
      EMbase, CNKI, CBM, VIP and Wan Fang Databases from inception to May 2012. Studies
      were selected using specific inclusion and exclusion criteria. A systematic
      review and meta-analysis was performed on the association between HIF-1alpha
      expression and clinical outcomes in lung cancer patients. All analyses were
      performed using the Revman 5.1 software. RESULTS: A total of 30 studies were
      identified as eligible for the systematic review and meta-analysis. The
      expression of HIF-1alpha was significantly higher than those in normal lung
      tissue; and III-IV stage, lymph node metastasis, poorly differentiation, squamous
      cell carcinoma and small cell lung cancer (SCLC) were significantly higher than
      those in I-II stage, no lymph node metastasis, well differentiation,
      adenocarcinomas and non small cell lung cancer (NSCLC), respectively (odds ratio
      (OR) = 19.00, 95% confidence interval (CI):12.12-29.78, p <0.00001; OR = 0.23,
      95% CI:0.14-0.36, p <0.00001; OR = 3.72, 95% CI:2.38-5.80, p <0.00001; OR = 0.47,
      95% CI:0.31-0.70, p <0.00002, OR = 0.24, 95% CI:0.07-0.77, p = 0.02; OR = 0.78,
      95% CI:0.63-0.98, p = 0.03). VEGF and CA IX positive expression in HIF-1alpha
      positive tumour tissues were significantly higher than those in HIF-1alpha
      negative tumour tissues, respectively (OR = 3.23, 95% CI: 1.90-5.46, p <0.0001;
      OR = 3.84, 95% CI: 2.10-7.03, p <0.0001). The positive HIF-1alpha tumour tissues
      of patients had lower 5-year survival rates (OR = 0.13, 95% CI: 0.03-0.47, p =
      0.002) and overall survival (relative risk (RR) = 1.68, 95% CI: 1.12-2.50, p =
      0.01). CONCLUSIONS: HIF-1alpha is related to a differing degree of lung cancer
      cell, lymph node metastasis, post-operative survival time and histology (NSCLC
      vs. SCLC, adenocarcinomas vs. squamous cell carcinoma). HIF-1 alpha , which
      combines other proteins, such as vascular endothelial growth factor (VEGF) or CA
      IX, might serve as important parameters in evaluating biological behaviour and
      prognosis of lung cancer; it will be of benefit to clinical treatment and
      prognostic evaluation.

PMID- 24018852
TI  - The inhibitory effects of the bioactive components isolated from Scutellaria
      baicalensis on the cellular uptake mediated by the essential solute carrier
      transporters.
AB  - Solute carrier transporters (SLCs), in particular the organic anion transporters
      (OATs), OAT polypeptides (OATPs), and organic cation transporters (OCTs/OCTNs),
      are the important membrane proteins responsible for the cellular influx of
      various drugs. Baicalein (BA), baicalin (BG), and wogonin (WG) are the three
      major bioactive components of Scutellaria baicalensis. In this study, we
      evaluated the inhibitory effects of BA, BG, and WG on the cellular uptake of
      specific substrates mediated by the essential SLCs in human embryonic kidney-293
      cells. Our data demonstrated that BA and WG significantly inhibit the OAT1-, OAT3
      , and OATP1B3-mediated uptake; BG effectively reduces the influx of substrates of
      OAT3, OAT4, OATP1B3, and OATP2B1; WG is a potent inhibitor of OCT3. Our further
      kinetic analysis derived the IC50 values of these compounds with pronounced
      inhibitory effects on SLCs, particularly the inhibitions of WG on OAT1 and OCT3
      and that of BA and WG on OAT3. Our study comprehensively evaluated the inhibitory
      effects of three bioactive components of Scutellaria baicalensis on the uptake of
      specific substrates mediated by the essential SLC transporters, which suggested
      that precautions will be needed when coadministrating drugs with Scutellaria
      baicalensis so as to prevent the unfavorable drug-drug/herb interactions in
      human.

PMID- 24018851
TI  - Very small embryonic-like stem cells (VSELs) represent a real challenge in stem
      cell biology: recent pros and cons in the midst of a lively debate.
AB  - The concept that adult tissue, including bone marrow (BM), contains early
      development cells with broader differentiation potential has again been recently
      challenged. In response, we would like to review the accumulated evidence from
      several independent laboratories that adult tissues, including BM, harbor a
      population of very rare stem cells that may cross germ layers in their
      differentiation potential. Thus, the BM stem cell compartment hierarchy needs to
      be revisited. These dormant, early-development cells that our group described as
      very small embryonic-like stem cells (VSELs) most likely overlap with similar
      populations of stem cells that have been identified in adult tissues by other
      investigators as the result of various experimental strategies and have been
      given various names. As reported, murine VSELs have some pluripotent stem cell
      characteristics. Moreover, they display several epiblast/germline markers that
      suggest their embryonic origin and developmental deposition in adult BM.
      Moreover, at the molecular level, changes in expression of parentally imprinted
      genes (for example, Igf2-H19) and resistance to insulin/insulin-like growth
      factor signaling (IIS) regulates their quiescent state in adult tissues. In
      several emergency situations related to organ damage, VSELs can be activated and
      mobilized into peripheral blood, and in appropriate animal models they contribute
      to tissue organ/regeneration. Interestingly, their number correlates with
      lifespan in mice, and they may also be involved in some malignancies. VSELs have
      been successfully isolated in several laboratories; however, some investigators
      experience problems with their isolation. 

PMID- 24018853
TI  - Phytogeography of Najas gracillima (Hydrocharitaceae) in North America and its
      cryptic introduction to California.
AB  - PREMISE OF THE STUDY: The discontinuous North American distribution of Najas
      gracillima has not been explained satisfactorily. Influences of extirpation,
      nonindigenous introduction, and postglacial migration on its distribution were
      evaluated using field, fossil, morphological, and molecular data. Najas is a
      major waterfowl food, and appropriate conservation measures rely on accurate
      characterization of populations as indigenous or imperiled. * METHODS: Seed
      lengths of N. gracillima from native Korean populations, a nonindigenous Italian
      population, and North American populations were compared using digital image
      analysis. DNA sequence analyses from these regions provided nine nrITS genotypes
      and eight cpDNA haplotypes. * KEY RESULTS: Najas gracillima seeds from Eurasia
      and California are shorter than those from eastern North America. Nuclear and
      chloroplast DNA sequences of N. gracillima from Korea and Italy were identical to
      California material but differed from native eastern North American plants.
      Eastern North American specimens of N. gracillima at localities above the last
      glacial maximum boundary were identical or similar genetically to material from
      the northeastern United States and Atlantic Coastal Plain and Piedmont but
      divergent from plants of the Interior Highlands-Mississippi Embayment region. *
      CONCLUSIONS: In California, N. gracillima is nonindigenous and introduced from
      Asia. In eastern North America, populations that colonized deglaciated areas were
      derived primarily from refugia in the Atlantic Coastal Plain and Piedmont.
      Genetic data indicate initial postglacial migration to northeastern North
      America, with subsequent westward dispersal into the Upper Great Lakes. These
      results differentiate potentially invasive California populations from seriously
      imperiled indigenous eastern North American populations.

PMID- 24018854
TI  - Deficiency of phytochrome B alleviates chilling-induced photoinhibition in rice.
AB  - PREMISE OF THE STUDY: Food crops of tropical origins, such as rice, are often
      cultivated in areas with suboptimal temperature regimes. The rice phytochrome B
      deficient mutant (phyB) is tolerant of chilling temperatures compared with the
      wild type (WT) under low irradiance, and unsaturated fatty acids (USFAs) of
      membrane lipids have been shown to play an important role in chilling resistance.
      However, the relationship between phytochrome B and membrane lipids has not been
      empirically investigated. * METHODS: We assessed various photosynthesis indexes
      in phyB and WT rice: chlorophyll content, maximal photochemical efficiency
      (Fv/Fm) of photosystem II (PSII), the quantum yield of PSII electron transport
      (PhiPSII), the percentage of oxidizable P700 (P700), nonphotochemical quenching
      (NPQ), and the de-epoxidized ratio of xanthophyll cycle (A+Z)/(V+A+Z). We also
      analyzed the ultrastructure and fatty acid desaturases (FADs) and glycerol-3
      phosphate acyltransferase (GPAT) genes of the chloroplasts using transmission
      electron microscopy and real-time PCR. * RESULTS: After a chilling treatment of
      24 h, chloroplast damage and USFA content reduction were more severe in the WT
      than in the phyB mutant. Genes involved in the synthesis of USFAs in membranes
      such as FADs and GPAT were more stable in phyB than in WT. Chlorophyll content,
      Fv/Fm, PhiPSII, and P700 decreased more slowly under chilling stress and
      recovered more rapidly under optimal conditions in phyB than in WT. The
      (A+Z)/(V+A+Z) and NPQ increased more rapidly in phyB than in the WT after 24 h of
      chilling treatment. * CONCLUSIONS: Phytochrome B deficiency in rice with more
      stabilized chloroplast structure and higher USFA content in membrane lipids could
      alleviate chilling-induced photoinhibition.

PMID- 24018855
TI  - Propagule pressure, genetic structure, and geographic origins of Chondrilla
      juncea (Asteraceae): an apomictic invader on three continents.
AB  - PREMISE OF THE STUDY: Assessing propagule pressure and geographic origins of
      invasive species provides insight into the invasion process. Rush skeletonweed
      (Chondrilla juncea; Asteraceae) is an apomictic, perennial plant that is invasive
      in Australia, South America (Argentina), and North America (Canada and the United
      States). This study comprehensively compares propagule pressure and geographic
      structure of genotypes to improve our understanding of a clonal invasion and
      enhance management strategies. * METHODS: We analyzed 1056 native range plants
      from Eurasia and 1156 plants from three invaded continents using amplified
      fragment length polymorphism (AFLP) techniques. We used measures of diversity
      (Simpson's D) and evenness (E), analysis of molecular variance, and Mantel tests
      to compare invasions, and genotype similarity to determine origins of invasive
      genotypes. * KEY RESULTS: We found 682 unique genotypes in the native range, but
      only 13 in the invaded regions. Each invaded region contained distinct AFLP
      genotypes, suggesting independent introduction events, probably with different
      geographic origins. Relatively low propagule pressure was associated with each
      introduction around the globe, but levels of among-population variation differed.
      We found exact AFLP genotype matches between the native and invaded ranges for
      five of the 13 invasive genotypes. * CONCLUSIONS: Invasion dynamics can vary
      across invaded ranges within a species. Intensive sampling for molecular analyses
      can provide insight for understanding intraspecific invasion dynamics, which can
      hold significance for the management of plant species, especially by finding
      origins and distributions of invasive genotypes for classical biological control
      efforts.

PMID- 24018856
TI  - Limited hybridization across an edaphic disjunction between the gabbro-endemic
      shrub Ceanothus roderickii (Rhamnaceae) and the soil-generalist Ceanothus
      cuneatus.
AB  - PREMISE OF THE STUDY: Hybridization is thought to have played an important role
      in diversification of the speciose shrub genus Ceanothus; putative hybrid species
      have been described, and data suggest that intrinsic barriers may not exist among
      closely related species. However, the extent to which hybridization occurs in the
      wild is not known, and little is understood about how extrinsic factors such as
      soil chemistry may influence the process. The present research focuses on the
      gabbro-endemic C. roderickii and the closely related soil-generalist C. cuneatus.
      Though the species occur peripatrically, they remain distinct across an edaphic
      disjunction. * METHODS: AFLP was used to quantify hybridization and
      introgression. Biological data and experiments were used to test for prezygotic
      isolation. Growth trials were used to test for local adaptation and selection
      against hybrids. * KEY RESULTS: Ceanothus cuneatus and C. roderickii were
      strongly differentiated morphologically and genetically, despite a lack of
      evidence for prezygotic barriers. Hybrids and back-crosses were present but
      infrequent. Finally, there was selection against hybrids in nonnative soil. *
      CONCLUSIONS: There is little genetic exchange between the focal species across an
      edaphic disjunction, despite the absence of prezygotic barriers. This result
      implies that soil conditions, as well as other extrinsic factors, should be
      considered as forces that may restrict hybridization and gene flow in Ceanothus,
      influencing local adaptation and speciation. Findings presented here are
      significant because they imply that exchange of genetic material between plants
      may be limited directly by the abiotic environment, rather than by the biology of
      the plants.

PMID- 24018857
TI  - A new approach for the study of the chemical composition of bordered pit
      membranes: 4Pi and confocal laser scanning microscopy.
AB  - PREMISE OF THE STUDY: Coniferous bordered pits are some of the most unique and
      fascinating microstructures of the lignified cell wall. The pit membrane consists
      of a margo and a torus region, hence facilitating both xylary water transport and
      also limiting air intrusion by pit aspiration. Additionally, bordered pits have
      been reported to play a decisive role in the control of rapid liquid flow via the
      shrinkage and swelling of pectin. The study of the nanostructural chemical
      composition of pit membranes has been difficult with common imaging/chemical
      techniques, which involve drying and/or coating of the samples. * METHODS: Using
      fluorescent tagging and antibodies specific to pectin, and a His-tagged cellulose
      binding module that reacts with crystalline cellulose, in combination with
      confocal laser scanning microscopy (CLSM) and 4Pi microscopy, we generated three
      dimensional images of intact pit membranes. * KEY RESULTS: With enhanced
      resolution in the z-direction of the 4Pi microscope, it was possible to
      distinguish cellulose in the torus and the margo strands of Pinus strobus. The
      torus was surrounded by pectin, and a pectin ring was found at the margin of the
      torus. We also found differences in the structure of the pit membrane between
      aspirated and unaspirated pits, with a displacement of pectin to form a ring-like
      structure, the collapse of a void in the interior of the torus, and an apparent
      change in the chemical structure of cellulosic components, during the aspiration
      process. * CONCLUSIONS: The 4Pi microscope is well suited to scanning pit
      membranes to discover previously undescribed anatomical features in bordered pits
      and can provide information on chemical composition when used in combination with
      appropriate probes.

PMID- 24018858
TI  - First record of Todea (Osmundaceae) in South America, from the early Eocene
      paleorainforests of Laguna del Hunco (Patagonia, Argentina).
AB  - PREMISE OF THE STUDY: The early Eocene Laguna del Hunco caldera-lake paleoflora
      (ca. 52 Ma) from Chubut Province, Argentina, is notably diverse and includes many
      conifer and angiosperm lineages that are extinct in South America but extant in
      Australasian rainforests. No ferns have been previously described from Laguna del
      Hunco. We describe and interpret a new species of fossil Osmundaceae based on
      fertile and sterile pinnae. * METHODS: The fossil specimens were compared with
      other extant and fossil Osmundaceae based on living and herbarium material and
      published descriptions. A morphological matrix based on 29 characters was
      constructed for 17 living species in Osmundaceae, four species assigned to the
      fossil genus Todites, and the new fossil species. Phylogenetic analyses were
      conducted under parsimony using morphology and total evidence matrices. * KEY
      RESULTS: Both the new fossil and the Todites species were consistently resolved
      within the leptopteroid clade of Osmundaceae, and the new species resolved in a
      clade with the two living Todea species, which are now restricted to Australia,
      New Guinea, New Zealand, and southern Africa. * CONCLUSIONS: Todea amissa sp.
      nov. is the first record of Todea, living or fossil, in South America and only
      the second fossil record worldwide. The distribution of extant Todea on Gondwanan
      continents other than South America is broadly shared with other taxa from Laguna
      del Hunco, further indicating that a large component of this flora represents a
      Gondwanic biome that is no longer found on the South American continent.

PMID- 24018859
TI  - Niche evolution through time and across continents: The story of Neotropical
      Cedrela (Meliaceae).
AB  - PREMISE OF THE STUDY: Climatic and geological changes have been considered as
      major drivers of biological diversification. However, it has been generally
      assumed that lineages retain common environmental affinities, suggesting a
      limited capacity to switch their climatic niche. We tested this assumption with a
      study of the evolution of climatic niches in the Neotropical tree genus Cedrela
      (Meliaceae). * METHODS: We combined distribution models of extant Cedrela with a
      dated molecular phylogeny based on one nuclear (ITS) and three plastid markers
      (psbA-trnH, trnS-G and psbB-T-N) to reconstruct the evolutionary dynamics of
      climatic niches. We calculated relative disparity of climatic tolerances over
      time to test for niche evolution within subclades or divergence between subclades
      and conservatism among closely related groups. Published fossil records and
      studies on paleosols were evaluated for the distribution and climatic conditions
      of extinct Cedrela. * KEY RESULTS: The fossil record of Cedrela suggested a major
      biome shift from paratropical conditions into warm-temperate seasonal climates in
      the Early Oligocene of western North America. In the Miocene, Cedrela extended
      from North America (John Day Formation, Oregon, USA) to southern Central America
      (Gatun, Panama). Diversification in the early evolutionary history was mainly
      driven by changes in precipitation. Temperature had an increasing impact on
      ecological diversification of the genus from the Miocene onwards. Sister-species
      comparisons revealed that recent speciation events may be related to divergence
      of climatic tolerances. * CONCLUSIONS: Our study highlights the complexity of
      climatic niche dynamics, and shows how conservatism and evolution have acted on
      different temporal scales and climatic parameters in Cedrela.

PMID- 24018860
TI  - Organic field-effect transistor sensors: a tutorial review.
AB  - The functioning principles of electronic sensors based on organic semiconductor
      field-effect transistors (OFETs) are presented. The focus is on biological
      sensors but also chemical ones are reviewed to address general features. The
      field-induced electronic transport and the chemical and biological interactions
      for the sensing, each occurring at the relevant functional interface, are
      separately introduced. Once these key learning points have been acquired, the
      combined picture for the FET electronic sensing is proposed. The perspective use
      of such devices in point-of-care is introduced, after some basics on analytical
      biosensing systems are provided as well. This tutorial review includes also a
      necessary overview of the OFET sensing structures, but the focus will be on
      electronic rather than electrochemical detection. The differences among the
      structures are highlighted along with the implications on the performance level
      in terms of key analytical figures of merit such as: repeatability, sensitivity
      and selectivity. 

PMID- 24018861
TI  - On-line electrochemical reduction of disulfide bonds: improved FTICR-CID and -ETD
      coverage of oxytocin and hepcidin.
AB  - Particularly in the field of middle- and top-down peptide and protein analysis,
      disulfide bridges can severely hinder fragmentation and thus impede sequence
      analysis (coverage). Here we present an on-line/electrochemistry/ESI-FTICR-MS
      approach, which was applied to the analysis of the primary structure of oxytocin,
      containing one disulfide bridge, and of hepcidin, containing four disulfide
      bridges. The presented workflow provided up to 80% (on-line) conversion of
      disulfide bonds in both peptides. With minimal sample preparation, such reduction
      resulted in a higher number of peptide backbone cleavages upon CID or ETD
      fragmentation, and thus yielded improved sequence coverage. The cycle times,
      including electrode recovery, were rapid and, therefore, might very well be
      coupled with liquid chromatography for protein or peptide separation, which has
      great potential for high-throughput analysis.

PMID- 24018862
TI  - Analysis of overlapped and noisy hydrogen/deuterium exchange mass spectra.
AB  - Noisy and overlapped mass spectrometry data hinder the sequence coverage that can
      be obtained from hydrogen deuterium exchange analysis, and places a limit on the
      complexity of the samples that can be studied by this technique. Advances in
      instrumentation have addressed these limits, but as the complexity of the
      biological samples under investigation increases, these problems are re
      encountered. Here we describe the use of binomial distribution fitting with
      asymmetric linear squares regression for calculating the accurate deuterium
      content for mass envelopes of low signal or that contain significant overlap. The
      approach is demonstrated with a test data set of HIV Env gp140 wherein inclusion
      of the new analysis regime resulted in obtaining exchange data for 42 additional
      peptides, improving the sequence coverage by 11%. At the same time, the precision
      of deuterium uptake measurements was improved for nearly every peptide examined.
      The improved processing algorithms also provide an efficient method for
      deconvolution of bimodal mass envelopes and EX1 kinetic signatures. All these
      functions and visualization tools have been implemented in the new version of the
      freely available software, HX-Express v2.

PMID- 24018863
TI  - A novel strategy for targeting photodynamic therapy. Molecular combo of
      photodynamic agent zinc(II) phthalocyanine and small molecule target-based
      anticancer drug erlotinib.
AB  - In this study, two phthalocyanine-erlotinib conjugates linked by an oligoethylene
      glycol chain have been synthesised and fully characterised. Having erlotinib as
      the targeting moiety, the two conjugates exhibited high specific affinity to
      HepG2 cancer cells and tumour tissues, therefore leading to high photodynamic
      activity. 

PMID- 24018864
TI  - Reflections on the aerobic fermentation stoichiometry of Crabtree positive
      yeasts.
AB  - In this communication a stoichiometric steady state model for Crabtree positive
      yeasts is proposed. The model is sufficiently simple to be corroborated by
      experimental data on the key metabolic events around Dcrit. The key feature of
      the model is that the bottleneck aperture for biomass production in the model of
      Sonnleitner and Kappeli, 1986 shrinks abruptly at Dcrit and continues to decrease
      with increasing dilution rate. A black box stoichiometric analysis of experiments
      reported in literature indicates that production of acetaldehyde might account
      for the abrupt shrinkage through a severe poisoning effect on the respiratory
      system.

PMID- 24018865
TI  - Molecularly imprinted photonic crystals for the direct label-free distinguishing
      of L-proline and D-proline.
AB  - Novel molecularly imprinted photonic crystals (IPCs) for the highly sensitive
      label-free detection of L-proline and for the chiral recognition of L/D-proline
      were reported. A series of L-proline imprinted polyacrylamide photonic crystals
      (PAM-LPIPCs) and poly(acrylamide-co-acrylic acid) photonic crystals (PAM-co-AA
      LPIPCs) were fabricated via the in situ polymerization of polystyrene opal. The
      PAM-LPIPCs exhibit good molecular response in L-proline solutions and can be
      visualized by the naked eye much like a pH test paper. The concentration of
      imprinted molecules (L-proline) in aqueous solution can be detected by the
      chromatic signal (structural color) or the optical signal (lambdamax).
      Furthermore, the responsivity and sensitivity of the PAM-co-AA-LPIPCs can be
      improved by increasing the amount of the imprinted content or the proportion of
      AA, or by decreasing the ratio of the cross-linking agent. When all these factors
      were balanced, a PAM2-co-AA0.4-LP0.5 IPC with good strength, high responsivity,
      high sensitivity and specific molecular recognition was obtained. It is found
      that the presented crystals can show obvious response to L-proline solution even
      at a low concentration of 1%. The PAM2-co-AA0.4-LP0.5 IPC not only very
      selectively distinguishes between L-proline and nicotinic acid, but it is also
      good at chiral recognition between L-proline and D-proline. What is more, the
      response is rapid and reversible and the IPC is recyclable.

PMID- 24018866
TI  - Cardiorespiratory and muscular responses to simulated upwind sailing exercise in
      Optimist sailors.
AB  - The aim of this work was to gain more insight into the cardiorespiratory and
      muscular (m. vastus lateralis) responses to simulated upwind sailing exercise in
      10 high-level male and female Optimist sailors (10.8-14.4 years old). Hiking
      strap load (HSL) and cardiorespiratory variables were measured while exercising
      on a specially developed Optimist sailing ergometer. Electromyography (EMG) was
      used to determine mean power frequency (MPF) and root mean square (RMS). Near
      infrared spectroscopy was used to measure deoxygenated Hemoglobin and Myoglobin
      concentration (deoxy[Hb+Mb]) and re-oxygenation. Results indicated that HSL and
      integrated EMG of the vastus lateralis muscle changed in accordance with the
      hiking intensity. Cardiorespiratory response demonstrated an initial significant
      increase and subsequently steady state in oxygen uptake (VO2), ventilation (VE),
      and heart rate (HR) up to circa 40% VO2peak, 30% VEpeak and 70% HRpeak
      respectively. At muscle level, results showed that highly trained Optimist
      sailors manage to stabilize the muscular demand and fatigue development during
      upwind sailing (after an initial increase). However, approaching the end of the
      hiking exercise, the MPF decrease, RMS increase, and deoxy[Hb+Mb] increase
      possibly indicate the onset of muscle fatigue.

PMID- 24018867
TI  - Global approach for transient shear wave inversion based on the adjoint method: a
      comprehensive 2D simulation study.
AB  - Shear wave imaging (SWI) maps soft tissue elasticity by measuring shear wave
      propagation with ultrafast ultrasound acquisitions (10 000 frames s(-1)). This
      spatiotemporal data can be used as an input for an inverse problem that
      determines a shear modulus map. Common inversion methods are local: the shear
      modulus at each point is calculated based on the values of its neighbour (e.g.
      time-of-flight, wave equation inversion). However, these approaches are sensitive
      to the information loss such as noise or the lack of the backscattered signal. In
      this paper, we evaluate the benefits of a global approach for elasticity
      inversion using a least-squares formulation, which is derived from full waveform
      inversion in geophysics known as the adjoint method. We simulate an acoustic
      waveform in a medium with a soft and a hard lesion. For this initial application,
      full elastic propagation and viscosity are ignored. We demonstrate that the
      reconstruction of the shear modulus map is robust with a non-uniform background
      or in the presence of noise with regularization. Compared to regular local
      inversions, the global approach leads to an increase of contrast (~+3 dB) and a
      decrease of the quantification error (~+2%). We demonstrate that the inversion is
      reliable in the case when there is no signal measured within the inclusions like
      hypoechoic lesions which could have an impact on medical diagnosis. 

PMID- 24018868
TI  - Rhinoplasty and brow modification: a powerful combination.
AB  - BACKGROUND: Plastic surgeons have long recognized the importance of performing
      chin augmentation concurrent with a rhinoplasty to achieve facial balance.
      However, few surgeons consider the benefits of combining a rhinoplasty with brow
      modification to achieve a better aesthetic result. By increasing the size of the
      middle third of the face, the nose will automatically appear smaller. OBJECTIVE:
      The authors describe anatomical dissections that provided perspective on the
      facial anatomy of the areas being studied and report the results of concurrent
      browlift and rhinoplasty procedures in a retrospective series of patients.
      METHODS: The present study consisted of 2 parts: anatomical dissections and a
      retrospective chart review. The nose and central forehead area were dissected in
      7 fresh cadavers at the time of autopsy to understand the anatomical relationship
      between the various muscles in the radix/glabellar region and to assess the
      muscle resection occurring in the clinical procedures. We also reviewed the
      charts of 24 patients who underwent combined rhinoplasty and brow modification
      with the senior author (R.K.D.) during a 2-year period (July 2010 to June 2012).
      Younger patients underwent a central browlift (CBL) with screw fixation, while
      older patients (ages 34-60 years) underwent full 5-incision endoscopic forehead
      lifting. RESULTS: The age range for patients in this series was 14 to 60 years.
      Two patients were men and 22 were women. There were 12 primary and 12 secondary
      procedures in the series; 13 patients underwent CBL and 11 had EFL. The mean
      follow-up was 18 months. One patient had a persistent fluid accumulation in the
      glabellar region, which required drainage. One patient requested additional
      refinement of her nasal tip. CONCLUSION: Modification of the central brow can
      dramatically change the aesthetic polygons of the nose/glabellar region. A CBL
      with radix/glabellar muscle excision is important in younger patients who need a
      well-defined nasion and older secondary patients who feel that the upper third of
      their nose is still heavy. A full EBL can enhance the facial appearance of older
      patients in whom a rhinoplasty alone would have a modest impact.

PMID- 24018869
TI  - Photogrammetric analysis of eyebrow and upper eyelid dimensions in South Indians
      and Malaysian South Indians.
AB  - BACKGROUND: The eyebrow and eyelid are important sexually dimorphic and ethnic
      features of the face. In cosmetic surgery, maintenance of these landmarks is
      important to obtaining satisfactory results. OBJECTIVES: The authors quantify the
      dimension and position of the eyebrow and eyelid in South Indians and Malaysian
      South Indians and assess whether significant differences exist between the sexes
      and ethnic groups. METHODS: Evaluation of eyebrow and upper eyelid was performed
      on standardized photographs of 200 South Indian and 200 Malaysian South Indian
      subjects, aged 18 to 26 years. We measured eyebrow thickness, apex to lateral
      limbus distance, apex to lateral canthus distance, interbrow distance, medial end
      of the eyebrow to medial canthus, lateral end of the eyebrow to lateral canthus,
      eyebrow height, eyebrow apex inclination, and pretarsal skin height. The measured
      values were evaluated by an independent t test. We also assessed the prevalence
      of double lid crease and types of epicanthus and eyebrow apex positions. RESULTS:
      A significant difference was found between women in the South Indian and
      Malaysian South Indian groups for eyebrow apex to lateral limbus distance, medial
      end to medial canthus, pretarsal skin height, eyebrow height, and eyebrow apex
      inclination. Male groups showed significant ethnic difference for eyebrow apex to
      lateral limbus distance. Sexual dimorphism was found for all measurement
      categories. A double crease fold appeared in 99% of the subjects. Only epicanthus
      tarsalis (95%) and epicanthus superciliaris (5%) appeared in the subjects. Four
      types of eyebrow apex position were found. CONCLUSIONS: Ethnic and sex
      differences exist for eyebrow and eyelid dimensions in the 2 groups we studied.
      Knowledge of these trends is significant during surgical planning to obtain ideal
      outcomes.

PMID- 24018870
TI  - Interplay of cytoskeletal activity and lipid phase stability in dynamic protein
      recruitment and clustering.
AB  - Recent experiments have revealed that some membrane proteins aggregate to form
      clusters. This type of process has been proven to be dynamic and to be actively
      maintained by external kinetics. Additionally, this dynamic recruiting is
      cholesterol- and actin-dependent, suggesting that raft organization and
      cytoskeleton rearrangement play a crucial role. In the present study, we propose
      a simple model that provides a general framework to describe the dynamical
      behavior of lipid-protein assemblies. Our results suggest that lipid-mediated
      interactions and cytoskeleton-anchored proteins contribute to the modulation of
      such behavior. In particular, we find a resonant condition between the membrane
      protein and cytoskeleton dynamics that results in the invariance of the ratio of
      clustered proteins that is found in in vivo experimental observations. 

PMID- 24018872
TI  - The first pelvic examination for an adolescent: is this rite of passage used to
      its full potential?
AB  - PURPOSE OF REVIEW: Adolescents' experiences of their first pelvic examination
      (external inspection, speculum examination and bimanual palpation) may have a
      marked influence on future experiences; why examination techniques and strategies
      for creating a positive experience of this situation need to be developed. This
      review addresses to what extent that ambition is reflected in recent literature.
      RECENT FINDINGS: The majority of articles on 'pelvic examination during
      adolescence' come from the United States, which skews the review's perspective.
      Several researchers recommend using investigations based on new technology rather
      than a pelvic examination when medical indications for a full examination are
      present. The profession's attitudes toward annual check-ups and pelvic
      examinations (in the United States) are currently debated, for teens as well as
      for adults.How to perform a first pelvic examination on an adolescent is not
      often discussed, nor are strategies for creating a positive experience of this
      event.The contexts in which a first pelvic examination is performed probably
      differ among societies. The Swedish and the US contexts are compared as an
      illustration; for example preventive healthcare and sex education is in Sweden
      the responsibility of schools, open for anybody and without admission fees.
      SUMMARY: Recent literature does not mirror a need for developing examination
      techniques and strategies for creating a positive experience of the first pelvic
      examination, nor for exploiting its maximal potential as a positive rite of
      passage.The ongoing US debate on indications for pelvic examinations and annual
      check-ups is even more relevant for adolescents, in whom contraindications need
      to be considered.

PMID- 24018871
TI  - Status of adolescent pelvic inflammatory disease management in the United States.
AB  - PURPOSE OF REVIEW: Pelvic inflammatory disease (PID) is a common and serious
      reproductive health disorder and disease rates remain unacceptably high among
      adolescent girls and young adult women in the United States. Despite data
      demonstrating that women experience major adverse health outcomes after PID,
      national recommendations for management of adolescents have become increasingly
      less cautious in an era of cost-containment. In this review, we take an
      alternative look at published data on adolescents with PID to frame the next
      steps for optimizing management for this vulnerable population. RECENT FINDINGS:
      Several findings emerge from review of the literature. First, there is limited
      evidence to guide the best practice strategies for adolescents with PID due to
      low enrolment of early and middle adolescents in national trials. Second,
      adolescents and adult women in the United States receive suboptimal treatment
      regimens per Centers for Disease Control and Prevention (CDC) standards. Third,
      available evidence suggests that adolescents are at an increased risk for poor
      adherence to CDC recommendations for self-care, reacquisition of sexually
      transmitted infections (STIs) and PID, and subsequent adverse reproductive health
      outcomes. SUMMARY: Efforts to develop and integrate adolescent-focused, evidence
      based strategies for PID management and prevention of subsequent STIs and
      recurrent PID are warranted.

PMID- 24018873
TI  - Adolescent relationship abuse and reproductive and sexual coercion among teens.
AB  - PURPOSE OF REVIEW: Adolescent relationship abuse (ARA) involves a range of
      coercive and violent behaviours in romantic or consensual relationships. ARA is
      prevalent and is associated with multiple poor reproductive and sexual health
      outcomes, especially for adolescent girls. RECENT FINDINGS: Recent studies and
      reviews of ARA research point to the prevalence of ARA, health consequences of
      ARA and the contribution of social and cultural norms to ARA perpetration, all of
      which can inform how to address ARA more effectively with adolescents. Emerging
      research on reproductive and sexual coercion among adolescents and technology
      based abuse is directly relevant to the reproductive and sexual healthcare of
      adolescents. SUMMARY: Current findings underscore the extent to which young,
      reproductive-aged women may particularly benefit from more effective methods to
      address ARA. In line with recent American Congress of Obstetricians and
      Gynecologists recommendations, clinicians should assess for and counsel their
      adolescent female patients about how ARA and reproductive and sexual coercion may
      influence adolescent girls' reproductive health. Recent evidence also highlights
      that ARA manifests in ways that may be less recognizable to clinicians, such as
      cyber dating abuse. Finally, ARA prevention and intervention efforts should
      continue to promote gender equity and address the social and cultural norms that
      shape adolescent girls' experiences of abuse.

PMID- 24018874
TI  - Primary ovarian insufficiency in the adolescent.
AB  - PURPOSE OF REVIEW: To raise awareness about the importance of early diagnosis of
      primary ovarian insufficiency (POI) in the adolescent. RECENT FINDINGS: Menstrual
      cycle irregularity or amenorrhea in the adolescent has historically been treated
      with oral contraceptives or ignored, with no evaluation done to determine the
      cause. However, it is now becoming clear that the health consequences of
      menstrual irregularities differ depending on the cause, and evaluation to
      determine the cause of menstrual irregularity is warranted. Although POI is
      classically diagnosed when menstrual cycle irregularity is accompanied by high
      circulating levels of gonadotropins and low estradiol, anti-Mullerian hormone is
      emerging as a biomarker of increasing importance. When POI is diagnosed, further
      evaluation including karyotype, FMR1 premutation analysis, and 21-hydroxylase or
      adrenal antibody is warranted. Girls at high risk for the development of POI
      (e.g. because of planned cancer treatment) should be offered the option of oocyte
      or ovarian tissue cryopreservation. SUMMARY: POI should be ruled out in
      adolescents with menstrual cycle irregularity. Early diagnosis of POI facilitates
      the individualization of therapy, as the health consequences of POI differ from
      those of other causes of menstrual cycle irregularity. In addition, recognition
      of premature oocyte depletion allows for the option of fertility preservation to
      be discussed when oocytes are still present.

PMID- 24018875
TI  - Management of vaginal agenesis.
AB  - PURPOSE OF REVIEW: Mayer-Rokitansky-Kuster-Hauser syndrome is undergoing new
      research outcomes involving genetics and management. RECENT FINDINGS: Recent
      literature supports a polygenic multifactorial genetic basis for the syndrome.
      Management is now predominantly by vaginal dilators and nonsurgical, but
      holistic. The future of uterine transplantation is discussed. SUMMARY: New
      developments open new possibilities for understanding the genetic basis of the
      disease, and research in this area will continue. Management in terms of
      fertility may have an added dimension if uterine transplantation and successful
      pregnancy outcome can be proven.

PMID- 24018876
TI  - Preventing urinary incontinence in women.
AB  - PURPOSE OF REVIEW: This review examines the evidence to date, analyzes specific
      risk factors and assesses the ability to prevent urinary incontinence in women,
      while providing clinical recommendations. More extraordinary risk factors such as
      ethnicity and race, mixed and fecal incontinence, iatrogenic and neurogenic
      factors should be discussed in a follow-up report. RECENT FINDINGS: Studies have
      revealed that certain factors place women at risk for developing urinary
      incontinence, including age, obesity, diabetes, pregnancy and delivery, high
      impact physical exercise factors and estrogen deficiency. SUMMARY: Healthcare
      providers should screen women who are at risk for developing urinary incontinence
      and institute specific interventions, specifically behavioral and even
      rehabilitative techniques, to prevent this prevalent and distressing condition.

PMID- 24018877
TI  - Current trends in surgical repair of pelvic organ prolapse.
AB  - PURPOSE OF REVIEW: Over the past decade, surgical prolapse correction has evolved
      significantly, taking a sharp turn in 2011 when the USFDA publicly questioned
      synthetic graft safety. This controversy has been widely publicized and debated
      amongst laymen and experts alike. This review summarizes current trends in mesh
      implantation for prolapse repair, highlighting the impact of the current
      controversy. RECENT FINDINGS: Recent studies revealed nonmesh prolapse repair may
      have better outcomes than previously reported; the USFDA states there is
      insufficient evidence to support vaginal mesh for apical or posterior compartment
      prolapse; mesh prolapse repair increased over the past decade, 75% of which was
      placed vaginally; approximately 30% of mesh prolapse repair is performed with
      hysterectomy and approximately 40% is performed with concomitant incontinence
      repair. Anterior and apical prolapse are most likely to include mesh and of
      apical repair procedures, minimally invasive approaches exceed laparotomy.
      SUMMARY: This year's population-based studies describe the impact of surgeon
      experience, prolapse compartment, and national trends in surgical technique on
      mesh prolapse repair. The impact of the recent investigation on future mesh use
      remains unknown.

PMID- 24018878
TI  - Suprapubic versus transurethral bladder catheterization following pelvic surgery.
AB  - PURPOSE OF REVIEW: There is uncertainty regarding the optimal method of achieving
      bladder drainage at the time of gynaecologic surgery. As both transurethral
      catheterization (TUC) and suprapubic catheterization (SPC) have the potential to
      cause harm, it is important that gynaecologists have accurate evidence upon which
      to base their bladder drainage policy. RECENT FINDINGS: Several clinical trials
      and meta-analyses have compared TUC with SPC in abdominal and pelvic surgery.
      Most recently, a large meta-analysis pooled the results of 12 gynaecological
      trials and found that the use of SPC leads to fewer urinary tract infections
      (UTIs) without any major complications and without increasing the duration of
      catheterization or length of hospital stay. SUMMARY: Robust evidence shows that
      SPC use leads to fewer UTIs when compared with TUC use in gynaecologic surgery.
      However, SPC use is associated with an increased incidence of minor
      complications. Future research should aim to assess the acceptability of both SPC
      and TUC to patients who are undergoing gynaecologic surgery. The quality of
      similar data in relation to rectal pelvic surgery is poor in comparison to the
      data on gynaecologic surgery.

PMID- 24018879
TI  - Modified approach to vaginal hysterectomy without initial colpotomy.
AB  - PURPOSE OF REVIEW: To evaluate the surgical technique and outcomes of women
      undergoing the modified approach to vaginal hysterectomy at Harbor-University of
      California, Los Angeles Medical Center from 2000 to 2011. A retrospective chart
      review was performed of all vaginal hysterectomy cases performed using the
      modified technique. RECENT FINDINGS: There is much evidence in favor of the
      safety of vaginal hysterectomy over other modes of hysterectomy, such as the
      lower overall incidence of vaginal cuff dehiscence, shorter hospital stays and
      faster recovery from surgery. The traditional method of performing vaginal
      hysterectomy involves early anterior or posterior colpotomy. At times, this may
      be difficult secondary to a flush cervix, distorted anatomy, and adhesions from
      prior surgeries or infection. At our teaching institution, however, we have
      adopted a different technique, initially developed by Dr. Reza Mohajer who is one
      of our faculty members and co-author of this article, that facilitates ligation
      of uterine vessels without initial attempt at colpotomy. This enables Ob/Gyn
      residents to safely and successfully perform vaginal hysterectomies despite large
      uterine size, nulliparity, flush cervix and previous pelvic surgery. SUMMARY:
      Modified approach to difficult vaginal hysterectomy facilitates performance of
      vaginal hysterectomy without need for initial anterior or posterior colpotomy.

PMID- 24018880
TI  - Effects of zinc on interleukins and antioxidant enzyme values in psoriasis
      induced mice.
AB  - The effects of zinc chloride (ZnCl2), disodium zinc ethylenediamine tetraacetate
      (Zn-EDTA), and zinc gluconate (Zn-GLU) on the antioxidant enzyme activities and
      levels of interleukins (ILs) in psoriasis-induced mice were studied. One hundred
      twenty female mice were randomly divided into six groups with 20 mice in each
      group: the control, positive control (PC), methotrexate (MTX), ZnCl2, Zn-EDTA,
      and Zn-GLU groups. All animals except the control group were given
      diethylstilbestrol for three consecutive days. After successfully inducing
      psoriasis, the control and PC groups were given normal saline (i.g.) daily while
      the remaining groups were given MTX, ZnCl2, Zn-EDTA, and Zn-GLU, respectively.
      The results revealed that the zinc supplementation could significantly (p < 0.05)
      inhibit mitosis in the mouse vaginal epithelium as methotrexate did and the
      inhibiting efficacy had nothing to do with the zinc forms. After ZnCl2, Zn-EDTA,
      and Zn-GLU supplementation, the levels of liver superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px), and catalase (CAT) activities increased and the
      concentration of malondialdehyde (MDA) decreased significantly (p < 0.05)
      compared to the PC group. The levels of SOD, CAT activity, and MDA level between
      each zinc supplementation group and MTX group were insignificant (p > 0.05). The
      zinc treatments also caused a significant (p < 0.05) decrease in the raised IL-2
      level of animal serum. The results obtained in the present work indicate the
      potential for zinc as a complementary pharmaceutical intervention for the
      treatment of topical psoriasis. 

PMID- 24018881
TI  - A zinc-dipicolylethylenediamine modified near infrared fluorophore for sensing of
      ATP.
AB  - The development of fluorescent probes for sensing of anions in biological
      environments is still a demanding task. Due to the structural versatility of
      biological active anions there are many challenges to cope with compared to
      fluoroionophores for the determination of metal cations. This concerns
      particularly the design of the recognition element, which has to provide a
      selective response, preferably unaffected by alterations of pH and ionic
      strength. Polyphosphate anions such as ATP are interesting targets in bioanalysis
      because they are involved in many enzymatic reactions and bear versatile
      biological functions. Zinc dipicolylamine complexes attached to fluorophores have
      been turned out to be promising candidates for ATP sensing with sufficient
      sensitivity and selectivity. We now report the first NIR probe that responds to
      ATP based on a zinc dipicolylethylenediamine receptor. It shows a "turn-on"
      fluorescence behavior which is selective to other polyphosphate species even at
      high ionic strength of the sample solution. 

PMID- 24018882
TI  - Female sex hormones are associated with the reduction of serum sodium and
      hypertension complications in patients with aldosterone-producing adenoma.
AB  - This study was conducted to evaluate gender-related differences in clinical
      characteristics and vascular complications in patients with aldosterone-producing
      adenomas (APA). Clinical characteristics, biochemical markers and incidence of
      vascular complications were compared by gender in 187 consecutive patients with
      APA confirmed by pathological diagnosis. Patients were separated into two groups
      based on ages either older or younger than 49 years, the average age of menopause
      among Chinese women (<49 y and >=49 y). Males had significantly higher BMI than
      females in the age group of <49 years (p = 0.017). In the <49 years group, males
      had significantly higher serum sodium levels (p = 0.003). However, no such gender
      differences in clinical characteristics were observed in patients >=49 years. A
      higher proportion of vascular complications was observed in males as compared to
      females aged <49 years but the difference was not statistically significant
      (51.4% vs. 34.8%, p = 0.105). The only gender difference observed in vascular
      complications between patients aged >=49 years was that a significantly greater
      proportion of males had cerebrovascular complication compared to females (p =
      0.006). Our data suggest that female sex hormones are implicated in reducing
      serum sodium concentration and vascular complications in female APA patients. 

PMID- 24018883
TI  - The combined use of the neutrophil-lymphocyte ratio and C-reactive protein level
      as prognostic predictors in adult patients with soft tissue sarcoma.
AB  - BACKGROUND: The aim of this study was to determine whether the combined use of
      the C-reactive protein (CRP) level and neutrophil-lymphocyte ratio (NLR) before
      treatment predicts disease-specific survival in adult patients with soft tissue
      sarcoma (STS). METHODS: We retrospectively reviewed 142 patients who presented
      with STS between 1995 and 2010. RESULTS: The NLR varied from 0.54 to 7.59. An
      elevated CRP level was observed in 36 patients before treatment. The patients
      with both an elevated CRP level and high NLR had a poorer disease-specific
      survival (46% at 5 years) than the patients with both a normal CRP level and low
      NLR (87% at 5 years) (P = 0.0005). The patients with both an elevated CRP level
      and high NLR also had a poorer disease-specific survival than the patients with
      either an elevated CRP level or high NLR (75.6% at five years) (P = 0.03). There
      were no significantly prognostic differences between the patients with a normal
      CRP level and low NLR and those with either an elevated CRP level or high NLR (P
      = 0.18). A multivariate analysis also showed the preoperative NLR and CRP level
      to be independent predictors of survival. CONCLUSIONS: We recommend the routine
      measurement of these markers to identify patients with a greater risk of death.

PMID- 24018884
TI  - [Comments on: comparative investigation on intraoperative "lung-protective
      ventilation" in abdominal surgery].

PMID- 24018885
TI  - A molecular and chemical perspective in defining melatonin receptor subtype
      selectivity.
AB  - Melatonin is primarily synthesized and secreted by the pineal gland during
      darkness in a normal diurnal cycle. In addition to its intrinsic antioxidant
      property, the neurohormone has renowned regulatory roles in the control of
      circadian rhythm and exerts its physiological actions primarily by interacting
      with the G protein-coupled MT1 and MT2 transmembrane receptors. The two melatonin
      receptor subtypes display identical ligand binding characteristics and mediate a
      myriad of signaling pathways, including adenylyl cyclase inhibition,
      phospholipase C stimulation and the regulation of other effector molecules. Both
      MT1 and MT2 receptors are widely expressed in the central nervous system as well
      as many peripheral tissues, but each receptor subtype can be linked to specific
      functional responses at the target tissue. Given the broad therapeutic
      implications of melatonin receptors in chronobiology, immunomodulation, endocrine
      regulation, reproductive functions and cancer development, drug discovery and
      development programs have been directed at identifying chemical molecules that
      bind to the two melatonin receptor subtypes. However, all of the melatoninergics
      in the market act on both subtypes of melatonin receptors without significant
      selectivity. To facilitate the design and development of novel therapeutic
      agents, it is necessary to understand the intrinsic differences between MT1 and
      MT2 that determine ligand binding, functional efficacy, and signaling
      specificity. This review summarizes our current knowledge in differentiating MT1
      and MT2 receptors and their signaling capacities. The use of homology modeling in
      the mapping of the ligand-binding pocket will be described. Identification of
      conserved and distinct residues will be tremendously useful in the design of
      highly selective ligands.

PMID- 24018886
TI  - Flavonoids from Orostachys japonicus A. Berger inhibit the invasion of LnCaP
      prostate carcinoma cells by inactivating Akt and modulating tight junctions.
AB  - Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or
      endothelial cells, and serve as a physical barrier to maintenance of homeostasis
      in body by controlling paracellular transport. Claudins are the most important
      molecules of the TJs, but paradoxically these proteins are frequently over
      expressed in cancers and their overexpression is implicated in the invasive
      potential of cancer. Hence, we investigated the effects of flavonoids extracted
      from Orostachys japonicus A. Berger (FEOJ) on TJs and the expression of claudins
      as well as cancer invasion along with in LnCaP human prostate cancer. FEOJ
      suppressed cancer cell motility and invasiveness at the concentrations where FEOJ
      did not show anti-proliferative activity. FEOJ increased transepithelial
      electrical resistance (TER) associated with tightening TJs, and suppressed
      expression of claudin proteins. Furthermore, FEOJ suppressed the activities of
      MMP-2 and -9 in a dose-dependent manner, which came from the activation of tissue
      inhibitor of metalloproteinases (TIMPs) by FEOJ. FEOJ suppressed migration and
      invasion by suppressing PI3K/Akt signaling pathway. Taken together, this study
      suggest that FEOJ suppresses cancer migration and invasion by tightening TJs
      through the suppression of claudin expression, and by suppressing MMPs in LnCaP
      human prostate cancer cells, which at least in part results from the suppression
      of PI3K/Akt signaling pathway.

PMID- 24018887
TI  - Molecular signatures in urologic tumors.
AB  - Urologic tumors continue to represent a huge fraction of cancer cases in the
      United States, with over 376,310 estimated new diagnoses in 2013. As with many
      types of tumors, urologic tumors vary greatly in their phenotype, ranging from
      minimally invasive to malignancies possessing great metastatic potential. The
      increasing need for more efficient and less invasive methods of cancer detection,
      as well as the ability to predict severity of the disease phenotype is readily
      evident--yet reliable methods remain elusive in a clinical setting today.
      Comprehensive panels of gene clusters are being developed toward the generation
      of molecular signatures in order to better diagnose urologic malignancies, and
      identify effective treatment strategies in the emerging era of personalized
      medicine. In this review, we discuss the current literature on the credibility
      and biomarker value of such molecular signatures in the context of clinical
      significance relating to the pathological aggressiveness of urologic tumors
      (prostate, bladder and renal cancer)--also exploiting their predictive potential
      in the response to treatment.

PMID- 24018888
TI  - CREG promotes the proliferation of human umbilical vein endothelial cells through
      the ERK/cyclin E signaling pathway.
AB  - Cellular repressor of E1A-stimulated genes (CREG) is a recently discovered
      secreted glycoprotein involved in homeostatic modulation. We previously reported
      that CREG is abundantly expressed in the adult vascular endothelium and
      dramatically downregulated in atherosclerotic lesions. In addition, CREG
      participates in the regulation of apoptosis, inflammation and wound healing of
      vascular endothelial cells. In the present study, we attempted to investigate the
      effect of CREG on the proliferation of vascular endothelial cells and to decipher
      the underlying molecular mechanisms. Overexpression of CREG in human umbilical
      vein endothelial cells (HUVEC) was obtained by infection with adenovirus carrying
      CREG. HUVEC proliferation was investigated by flow cytometry and 5-bromo-2'-deoxy
      uridine (BrdU) incorporation assays. The expressions of cyclins, cyclin-dependent
      kinases and signaling molecules were also examined. In CREG-overexpressing cells,
      we observed a marked increase in the proportion of the S and G2 population and a
      decrease in the G0/G1 phase population. The number of BrdU positively-stained
      cells also increased, obviously. Furthermore, silencing of CREG expression by
      specific short hairpin RNA effectively inhibited the proliferation of human
      umbilical vein endothelial cells (HUVEC). CREG overexpression induced the
      expression of cyclin E in both protein and mRNA levels to regulate cell cycle
      progression. Further investigation using inhibitor blocking analysis identified
      that ERK activation mediated the CREG modulation of the proliferation and cyclin
      E expression in HUVEC. In addition, blocking vascular endothelial growth factor
      (VEGF) in CREG-overexpressed HUVEC and supplementation of VEGF in CREG knocked
      down HUVEC identified that the pro-proliferative effect of CREG was partially
      mediated by VEGF-induced ERK/cyclin E activation. These results suggest a novel
      role of CREG to promote HUVEC proliferation through the ERK/cyclin E signaling
      pathway.

PMID- 24018889
TI  - Ibuprofen rescues abnormalities in periodontal tissues in conditional presenilin
      1 and presenilin 2 double knockout mice.
AB  - We used forebrain-specific conditional presenilin 1 (PS1) and presenilin 2 (PS2)
      double knockout mice (dKO mice) that exhibit symptoms of neurodegenerative
      diseases, especially Alzheimer's disease, to investigate whether ibuprofen can
      rescue brain and periodontal tissue abnormalities by attenuating the inflammatory
      response. Mandibles were dissected for alveolar bone-height analysis. Maxillae
      were fixed and decalcified for histological observation and osteoclast detection.
      ELISA measurements from the hippocampus, cortex, and gingiva of the mandibular
      incisor teeth were used to assay inflammatory mediators. We confirmed periodontal
      tissue abnormalities and inflammatory responses in brain and periodontal tissues
      in naive nine- and 12-month-old dKO mice. The other two groups of age-matched dKO
      mice that received 375-ppm ibuprofen treatment for six consecutive months
      exhibited significantly attenuated damage in periodontal tissues and reduction in
      several inflammation-related factors in brain and periodontal tissues. Our
      findings showed that the anti-inflammatory drug ibuprofen significantly decreased
      inflammation through the cyclooxygenase (COX) pathway in brain and periodontal
      tissues in dKO mice, and then attenuated abnormalities in periodontal tissues.
      This suggests that ibuprofen could be an ideal drug for preventing both nervous
      system and periodontal tissue damage caused by inflammatory responses.

PMID- 24018890
TI  - Green fluorescent protein (GFP)-based overexpression screening and
      characterization of AgrC, a Receptor protein of quorum sensing in Staphylococcus
      aureus.
AB  - Staphylococcus aureus AgrC is an important component of the agr quorum-sensing
      system. AgrC is a membrane-embedded histidine kinase that is thought to act as a
      sensor for the recognition of environmental signals and the transduction of
      signals into the cytoplasm. However, the difficulty of expressing and purifying
      functional membrane proteins has drastically hindered in-depth understanding of
      the molecular structures and physiological functions of these proteins. Here, we
      describe the high-yield expression and purification of AgrC, and analyze its
      kinase activity. A C-terminal green fluorescent protein (GFP) fusion to AgrC
      served as a reporter for monitoring protein expression levels in real time.
      Protein expression levels were analyzed by the microscopic assessment of the
      whole-cell fluorescence. The expressed AgrC-GFP protein with a C-terminal His
      tagged was purified using immobilized metal affinity chromatography (IMAC) and
      size exclusion chromatography (SEC) at yields of >= 10 mg/L, following
      optimization. We also assessed the effects of different detergents on membrane
      solubilization and AgrC kinase activity, and polyoxyethylene-(23)-lauryl-ether
      (Brij-35) was identified as the most suitable detergent. Furthermore, the
      secondary structural stability of purified AgrC was analyzed using circular
      dichroism (CD) spectroscopy. This study may serve as a general guide for
      improving the yields of other membrane protein preparations and selecting the
      appropriate detergent to stabilize membrane proteins for biophysical and
      biochemical analyses.

PMID- 24018891
TI  - Novel strategies for the prevention and treatment of biofilm related infections.
AB  - Biofilm formation by human bacterial pathogens on implanted medical devices
      causes major morbidity and mortality among patients, and leads to billions of
      dollars in healthcare cost. Biofilm is a complex bacterial community that is
      highly resistant to antibiotics and human immunity. As a result, novel
      therapeutic solutions other than the conventional antibiotic therapies are in
      urgent need. In this review, we will discuss the recent research in discovery of
      alternative approaches to prevent or treat biofilms. Current anti-biofilm
      technologies could be divided into two groups. The first group focuses on
      targeting the biofilm forming process of bacteria based on our understanding of
      the molecular mechanism of biofilm formation. Small molecules and enzymes have
      been developed to inhibit or disrupt biofilm formation. Another group of anti
      biofilm technologies focuses on modifying the biomaterials used in medical
      devices to make them resistant to biofilm formation. While these novel anti
      biofilm approaches are still in nascent phases of development, efforts devoted to
      these technologies could eventually lead to anti-biofilm therapies that are
      superior to the current antibiotic treatment.

PMID- 24018892
TI  - Longitudinal clinical follow-up of a large family with the R357P Twinkle
      mutation.
AB  - IMPORTANCE: Autosomal dominant progressive external ophthalmoplegia due to PEO1
      mutations is considered relatively benign, but no data about long-term
      progression of this disease have been reported. The aim of this study was to
      provide a 16-year clinical follow-up of autosomal dominant progressive external
      ophthalmoplegia due to the p.R357P gene mutation in PEO1. OBSERVATIONS: Twenty
      two members of an Irish-American family were examined in 1996, when PEO1
      sequencing revealed a c.1071G>C/p.R357P mutation in 9 of them. We reexamined the
      family in 2012 using a standardized clinical protocol. Autosomal dominant
      progressive external ophthalmoplegia due to the p.R357P PEO1 mutation is a late
      onset ocular myopathy beginning with ptosis and progressing slowly.
      Ophthalmoparesis, if present, is mild and evident only by neurological
      examination. CONCLUSIONS AND RELEVANCE: Our results are important for prognosis
      and genetic counseling.

PMID- 24018893
TI  - Relationship between metformin use, vitamin B12 deficiency, hyperhomocysteinemia
      and vascular complications in patients with type 2 diabetes.
AB  - Aim of the study was to clarify the relationship between metformin-induced
      vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in
      patients with type 2 diabetes. Serum B12 concentrations, homocysteine plasma
      levels, the presence of retinopathy and history of macroangiopathy (stroke or
      coronary heart disease) were analyzed in patients without renal dysfunction
      (serum creatinine<115 MUmol/L). Firstly, B12 status was analyzed in 62
      consecutive metformin-treated patients. Secondly, the relationship between B12,
      homocysteine and vascular complications was analyzed in 46 metformin-treated and
      38 age- and sex-matched non-metformin-treated patients. Among the 62 consecutive
      metformin-treated patients, B12 was deficient (<150 pmol/L) in 8 (13%) and
      borderline-deficient (150-220 pmol/L) in 18 (29%): the larger the metformin
      dosage, the lower the B12 (P=0.02, Spearman's rho=-0.30). There were independent
      correlations between metformin use and B12 lowering (P=0.02, r = -0.25), and B12
      lowering and elevation of homocysteine (P<0.01, r=-0.34). Elevation of
      homocysteine was a risk for retinopathy (P=0.02, OR 1.26, 95%CI 1.04-1.52). There
      was no significant relation between homocysteine and macroangiopathy. Correlation
      between B12 and homocysteine was stronger in metformin-treated (P<0.01, r=-0.48)
      than non-metformin-treated (P=0.04, r=-0.38) patients. In ten B12 deficient
      patients, B12 supplementation (1,500 MUg/day) for 2.2+/-1.0 months with continued
      use of metformin raised B12 levels: 152+/-42 and 299+/-97 pmol/L before and after
      treatment, respectively (P<0.01). Metformin-induced B12 lowering in diabetes was
      associated with elevation of homocysteine, and hyperhomocysteinemia was
      independently related to retinopathy. Metformin-induced B12 deficiency was
      correctable with B12 supplementation. 

PMID- 24018894
TI  - Super-hydrophobic yolk-shell nanostructure with enhanced catalytic performance in
      the reduction of hydrophobic nitroaromatic compounds.
AB  - A self-templating method to fabricate a super-hydrophobic yolk-shell nano-reactor
      was reported. Metal nanoparticles were encapsulated in the porous super
      hydrophobic shell. This super-hydrophobic catalyst showed excellent performance
      in the reduction of nitroaromatic compounds in aqueous phase and a positive
      correlation was found between the reaction rate and the hydrophobicity of the
      substrate. 

PMID- 24018895
TI  - Enhancing the electrochemical kinetics of high voltage olivine LiMnPO4 by
      isovalent co-doping.
AB  - We report here doping of Fe(2+) and/or Mg(2+) in LiMnPO4 cathode material to
      enhance its lithium storage performance and appraise the effect of doping. For
      this purpose, LiMn0.9Fe(0.1-x)MgxPO4/C (x = 0 and 0.05) and LiMn0.95Mg0.05PO4/C
      have been prepared by a ball mill assisted soft template method. These materials
      were prepared with similar morphology, particle size and carbon content. Amongst
      them, the isovalent co-doped LiMn0.9Fe0.05Mg0.05PO4/C sample shows better
      electrochemical performance compared to LiMn0.9Fe0.1PO4/C and LiMn0.95Mg0.05PO4/C
      samples. For instance, a lithium storage capacity of 159 mA h g(-1) is obtained
      at 0.1 C for LiMn0.9Fe0.05Mg0.05PO4/C material with a relatively low polarization
      of ~139 mV. This is in sharp contrast to LiMn0.9Fe0.1PO4/C and
      LiMn0.95Mg0.05PO4/C which show only 136.8 and 128.4 mA h g(-1) at 0.1 C with the
      polarization of ~222 and 334 mV respectively. Further, the
      LiMn0.9Fe0.05Mg0.05PO4/C electrode delivers discharge capacities of 155.8, 141.4,
      118.8, 104.6, 81.4 and 51.8 mA h g(-1) at 0.2, 0.5, 1, 2, 5 and 10 C
      respectively. This electrode material also retains a capacity of 116 mA h g(-1)
      at 1 C after 200 cycles, which is 96% of its initial capacity. Such improved
      cycling stability of LiMn0.9Fe0.05Mg0.05PO4/C is attributed to the suppressed Mn
      dissolution in the electrolyte compared to the other samples. Further, during the
      Li extraction process, delithiated phases created from the Fe(2+)/Fe(3+) redox
      reaction (~3.45 V) favor enhanced electrochemical activity of the succeeding
      Mn(2+)/Mn(3+) redox couples. The fully charged state (4.6 V) contains a partially
      lithiated phase owing to the presence of electrochemically inactive Mg(2+). The
      presence of such lithiated phase provides a favourable environment for the
      subsequent lithium insertion process. We also observe improved electronic
      conductivity and Li-ion diffusion for the co-doped sample compared to LiMnPO4
      doped with either Fe(2+) or Mg(2+) by impedance measurements. The improved
      storage performance of co-doped LiMnPO4 is thus explained in terms of (i)
      favorable extraction and insertion reactions and (ii) enhanced transport
      properties.

PMID- 24018896
TI  - ABC versus CAB for cardiopulmonary resuscitation: a prospective, randomized
      simulator-based trial.
AB  - QUESTIONS UNDER STUDY: After years of advocating ABC (Airway-Breathing
      Circulation), current guidelines of cardiopulmonary resuscitation (CPR) recommend
      CAB (Circulation-Airway-Breathing). This trial compared ABC with CAB as initial
      approach to CPR from the arrival of rescuers until the completion of the first
      resuscitation cycle. METHODS: 108 teams, consisting of two physicians each, were
      randomized to receive a graphical display of either the ABC algorithm or the CAB
      algorithm. Subsequently teams had to treat a simulated cardiac arrest. Data
      analysis was performed using video recordings obtained during simulations. The
      primary endpoint was the time to completion of the first resuscitation cycle of
      30 compressions and two ventilations. RESULTS: The time to execution of the first
      resuscitation measure was 32 +/- 12 seconds in ABC teams and 25 +/- 10 seconds in
      CAB teams (P = 0.002). 18/53 ABC teams (34%) and none of the 55 CAB teams (P =
      0.006) applied more than the recommended two initial rescue breaths which caused
      a longer duration of the first cycle of 30 compressions and two ventilations in
      ABC teams (31 +/- 13 vs.23 +/- 6 sec; P = 0.001). Overall, the time to completion
      of the first resuscitation cycle was longer in ABC teams (63 +/- 17 vs. 48 +/- 10
      sec; P <0.0001). CONCLUSIONS: This randomized controlled trial found CAB superior
      to ABC with an earlier start of CPR and a shorter time to completion of the first
      30:2 resuscitation cycle. These findings endorse the change from ABC to CAB in
      international resuscitation guidelines.

PMID- 24018897
TI  - Vitamin D concentrations and physical performance in competitive adolescent
      swimmers.
AB  - Serum vitamin D concentrations (25[OH]D) are associated with physical performance
      in the general population, but few studies have been published in athletes. 80
      competitive adolescent swimmers from both sexes were tested for serum 25(OH)D
      concentrations, grip strength, balance and swimming performance at several
      speeds. Spearman's correlations were used to examine the associations between
      25(OH)D concentrations and age-adjusted measures of performance. Performance
      parameters were also compared between vitamin D sufficient (n = 27), insufficient
      (25[OH]D ranging 20-29.9 ng/ml, n = 42), and deficient (25[OH]D < 20 ng/ ml, n =
      11) participants. No significant associations were found between serum 25(OH)D
      concentrations and any of the performance measures, with no significant
      differences found between vitamin D sufficient, insufficient and deficient
      participants. In competitive adolescent swimmers, serum vitamin D concentrations
      were not associated with strength, balance or swimming performance. Vitamin D
      insufficient/deficient swimmers did not have reduced performance. 

PMID- 24018898
TI  - Metamoodics: meta-analysis and bioinformatics resource for mood disorders.

PMID- 24018899
TI  - The triangular association of ADH1B genetic polymorphism, alcohol consumption and
      the risk of depression in older men.
AB  - Alcohol use, particularly alcohol abuse and dependence, are associated with
      increased risk of depression. Current diagnostic criteria suggest that the
      relationship is causal, but the evidence has only been derived from observational
      studies that are subject to confounding and bias. Given the logistic and ethical
      constraints that would be associated with a trial of alcohol use to prevent
      depression, we aimed to complete a Mendelian randomization study to determine if
      a genetic polymorphism associated with alcohol abuse and dependence (ADH1B
      rs1229984 G-->A) contributed to modulate the risk of depression in a community
      derived cohort of older men. This retrospective analysis of a cohort of 3873
      community-dwelling men aged 65-83 years living in the metropolitan region of
      Perth, Western Australia, investigated the triangular association between the
      rs1229984 G-->A polymorphism and alcohol use and, after 3.2-8.2 years, the
      presence of current depression or history of depression. The mean number of
      standard drinks consumed per week (n; standard deviation; range) according to
      genotype was AA 1.8 (17; 2.7; 0-7), GA 5.9 (262; 7.5; 0-35), GG 8.5 (3594; 10.9;
      0-140) (GG>AA, GG>GA; P<0.001). Consumption of 1 or 2 drinks per day decreased
      the odds of depression (n=610) by 30 and 40%, whereas consumption of more than
      six drinks daily more than doubled the odds of depression (odds ratio: 2.12, 95%
      confidence interval: 1.02, 4.40). The ADH1B rs1229984 G-->A polymorphism was not
      associated with current or past depression (P=0.857). In addition, the presence
      of the A allele did not interact with the alcohol use to modulate the risk of
      depression (P=0.725). These results suggest that alcohol consumption does not
      cause or prevent depression in older men.

PMID- 24018900
TI  - Cephalopods as vectors of harmful algal bloom toxins in marine food webs.
AB  - Here we summarize the current knowledge on the transfer and accumulation of
      harmful algal bloom (HAB)-related toxins in cephalopods (octopods, cuttlefishes
      and squids). These mollusks have been reported to accumulate several HAB-toxins,
      namely domoic acid (DA, and its isomers), saxitoxin (and its derivatives) and
      palytoxin (and palytoxin-like compounds) and, therefore, act as HAB-toxin vectors
      in marine food webs. Coastal octopods and cuttlefishes store considerably high
      levels of DA (amnesic shellfish toxin) in several tissues, but mainly in the
      digestive gland (DG)--the primary site of digestive absorption and intracellular
      digestion. Studies on the sub-cellular partitioning of DA in the soluble and
      insoluble fractions showed that nearly all DA (92.6%) is found in the cytosol.
      This favors the trophic transfer of the toxins since cytosolic substances can be
      absorbed by predators with greater efficiency. The available information on the
      accumulation and tissue distribution of DA in squids (e.g., in stranded Humboldt
      squids, Dosidicus gigas) is scarcer than in other cephalopod groups. Regarding
      paralytic shellfish toxins (PSTs), these organisms accumulate them at the
      greatest extent in DG >> kidneys > stomach > branchial hearts > posterior
      salivary glands > gills. Palytoxins are among the most toxic molecules identified
      and stranded octopods revealed high contamination levels, with ovatoxin (a
      palytoxin analogue) reaching 971 MUg kg-1 and palytoxin reaching 115 MUg kg-1
      (the regulatory limit for PlTXs is 30 MUg kg-1 in shellfish). Although the
      impacts of HAB-toxins in cephalopod physiology are not as well understood as in
      fish species, similar effects are expected since they possess a complex nervous
      system and highly developed brain comparable to that of the vertebrates. Compared
      to bivalves, cephalopods represent a lower risk of shellfish poisoning in humans,
      since they are usually consumed eviscerated, with exception of traditional dishes
      from the Mediterranean area.

PMID- 24018901
TI  - Hippuristanol reduces the viability of primary effusion lymphoma cells both in
      vitro and in vivo.
AB  - Primary effusion lymphoma (PEL) caused by Kaposi's sarcoma-associated herpesvirus
      (also known as human herpesvirus-8) shows serious lymphomatous effusion in body
      cavities. PEL is difficult to treat and there is no standard treatment strategy.
      Hippuristanol is extracted from Okinawan coral Isis hippuris, and inhibits
      translational initiation by blocking eukaryotic initiation factor 4A, an ATP
      dependent RNA helicase, binding to mRNA. Recently, there has been much interest
      in targeting translation initiation as an anticancer therapy. Here, we show that
      treatment of PEL cell lines with hippuristanol resulted in cell cycle arrest at
      G1 phase, and induced caspases activation and apoptosis. Hippuristanol also
      reduced the expression of cyclin D2, CDK2, CDK4, CDK6 and prosurvival XIAP and
      Mcl-1 proteins. Activation of activator protein-1, signal transducers and
      activators of transcription protein 3 and Akt pathways plays a critical role in
      the survival and growth of PEL cells. Hippuristanol suppressed the activities of
      these three pathways by inhibiting the expression of JunB, JunD, c-Fos, signal
      transducers and activators of transcription protein 3 and Akt proteins. In a
      xenograft mouse model that showed ascites and diffused organ invasion of PEL
      cells, treatment with hippuristanol significantly inhibited the growth and
      invasion of PEL cells compared with untreated mice. The results of the in vitro
      and in vivo experiments underline the potential usefulness of hippuristanol in
      the treatment of PEL. 

PMID- 24018902
TI  - Protective effects of higher cognitive reserve for neuropsychological and daily
      functioning among individuals infected with hepatitis C.
AB  - Higher levels of cognitive reserve (CR) can be protective against the
      neuropsychological manifestation of neural injury across a variety of clinical
      disorders. However, the role of CR in the expression of neurocognitive deficits
      among persons infected with the hepatitis C virus (HCV) is not well understood.
      Thirty-nine HCV-infected participants were classified as having either high (n =
      19) or low (n = 20) CR based on educational attainment, oral word reading, and IQ
      scores. A sample of 40 demographically comparable healthy adults (HA) was also
      included. All participants completed the Neuropsychological Assessment Battery,
      Delis-Kaplan Executive Function System, and Behavioral Rating Inventory of
      Executive Function, Adult Version (BRIEF-A). Linear regression analyses,
      controlling for gender, depression, and lifetime substance use disorders, found
      significant effects of HCV/CR group on verbal fluency, executive functions, and
      daily functioning T scores, but not in learning or the BRIEF-A. Pairwise
      comparisons revealed that the HCV group with low CR performed significantly below
      the HCV high CR and HA cohorts, who did not differ from one another. Findings
      indicate that higher levels of CR may be a protective factor in the
      neurocognitive and real-world manifestation of neural injury commonly associated
      with HCV infection. 

PMID- 24018903
TI  - Rates of autonomic dysfunction in HIV patients receiving antiretroviral therapy.

PMID- 24018904
TI  - Can we build a truly high performance computer which is flexible and transparent?
AB  - State-of-the art computers need high performance transistors, which consume ultra
      low power resulting in longer battery lifetime. Billions of transistors are
      integrated neatly using matured silicon fabrication process to maintain the
      performance per cost advantage. In that context, low-cost mono-crystalline bulk
      silicon (100) based high performance transistors are considered as the heart of
      today's computers. One limitation is silicon's rigidity and brittleness. Here we
      show a generic batch process to convert high performance silicon electronics into
      flexible and semi-transparent one while retaining its performance, process
      compatibility, integration density and cost. We demonstrate high-k/metal gate
      stack based p-type metal oxide semiconductor field effect transistors on 4 inch
      silicon fabric released from bulk silicon (100) wafers with sub-threshold swing
      of 80 mV dec(-1) and on/off ratio of near 10(4) within 10% device uniformity with
      a minimum bending radius of 5 mm and an average transmittance of ~7% in the
      visible spectrum.

PMID- 24018905
TI  - Simultaneous improvement of specificity and affinity of aptamers against
      Streptococcus mutans by in silico maturation for biosensor development.
AB  - In silico evolution with an in vitro system can facilitate the development of
      functional aptamers with high specificity and affinity. Although a general
      technique known as systematic evolution of ligand by exponential enrichment
      (SELEX) is an efficient method for aptamer selection, it sometimes fails to
      identify aptamers with sufficient binding properties. We have previously
      developed in silico maturation (ISM) to improve functions of aptamers based on
      genetic algorithms. ISM represents an intelligent exploitation of a random search
      within a defined sequence space to optimize aptamer sequences and improve their
      function of interest. Here we demonstrated a successful application of ISM of
      aptamers to simultaneously improve specificity and affinity for Streptococcus
      mutans with discovery of a core sequence, which was required to form a
      polymerized guanine quadruplex structure for target binding. We applied ISM to
      aptamers selected by whole-cell SELEX and identified an aptamer with up to 16
      fold improvement in affinity compared to its parent aptamers, and specificity was
      increased to show 12-fold more binding to S. mutans than to Lactobacillus
      acidophilus. Furthermore, we demonstrated a specific flow-through detection of S.
      mutans at a concentration range of 1 * 10(5) -10(8)  CFU/mL using the evolved
      aptamer immobilized on gold colloids.

PMID- 24018906
TI  - Characterization of hatch-size and growth rates of captive and wild-reared brown
      kiwi (Apteryx mantelli) chicks.
AB  - Avian growth rate patterns represent a trade off between a tissue's functional
      maturity and its capacity for growth. At the time of hatch, the brown kiwi
      (Apteryx mantelli) limb has a high level of maturity in order for the chick to be
      able to kick its way out of the shell and walk and forage independently from an
      early age. Growth curves of limb segments, bill length and bodyweight are
      presented for captive-reared, BNZ Operation Nest EggTM chicks over a period of 3
      months from the point of hatch. Some parameters were slightly larger in the
      females than in males at time of hatch, including the bill length. Growth in
      bodyweight began to slow earlier in males than in females. Regressions of limb
      and bill measurements over time showed linear patterns of growth instead of a
      sigmoidal curve as seen in other birds, probably due to the short period of
      observation. Bodyweight and bill length were then compared to these morphometrics
      in a wild population of kiwi. Captive-reared chicks were found to hatch with
      shorter bills and to increase in bodyweight at a faster rate than the wild birds.
      Rapid weight gain has been implicated in developmental limb deformities in other
      precocial and long-legged birds and should be avoided in captive kiwi.

PMID- 24018907
TI  - Placenta membranacea with placenta accreta: radiologic diagnosis and clinical
      implications.

PMID- 24018908
TI  - Systematic review of basic oral care for the management of oral mucositis in
      cancer patients.
AB  - PURPOSE: The purpose of this project was to evaluate research in basic oral care
      interventions to update evidence-based practice guidelines for preventing and
      treating oral mucositis (OM) in cancer patients undergoing radio- or
      chemotherapy. METHODS: A systematic review of available literature was conducted
      by the Basic Oral Care Section of the Mucositis Study Group of MASCC/ISOO. Seven
      interventions--oral care protocols, dental care, normal saline, sodium
      bicarbonate, mixed medication mouthwash, chlorhexidine, and calcium phosphate-
      were evaluated using the Hadorn (J Clin Epidemiol 49:749-754, 1996) criteria to
      determine level of evidence, followed by a guideline determination of one of the
      following: recommendation, suggestion, or no guideline possible, using
      Somerfield's (Classic Pap Cur Comments 4:881-886, 2000) schema. RESULTS: Fifty
      two published papers were examined by treatment population (radiotherapy,
      chemotherapy, and hematopoietic stem cell transplant) and by whether the
      intervention aimed to prevent or treat OM. The resulting practice suggestions
      included using oral care protocols for preventing OM across all treatment
      modalities and age groups and not using chlorhexidine mouthwash for preventing OM
      in adults with head and neck cancer undergoing radiotherapy. Considering
      inadequate and/or conflicting evidence, no guidelines for prevention or treatment
      of OM were possible for the interventions of dental care, normal saline, sodium
      bicarbonate, mixed medication mouthwash, chlorhexidine in patients receiving
      chemotherapy or hematopoietic stem cell transplant, or calcium phosphate.
      CONCLUSIONS: The evidence for basic oral care interventions supports the use of
      oral care protocols in patient populations receiving radiation and/or
      chemotherapy and does not support chlorhexidine for prevention of mucositis in
      head and neck cancer patients receiving radiotherapy. Additional well-designed
      research is needed for other interventions to improve the amount and quality of
      evidence guiding future clinical care.

PMID- 24018909
TI  - The importance of symptom surveillance during follow-up care of leukemia,
      bladder, and colorectal cancer survivors.
AB  - PURPOSE: We examined cancer survivors' experience of bothersome symptoms,
      association of symptom bother with health-related quality of life (HRQOL),
      survivors' perception of symptom care, and their symptom-related information
      needs. METHODS: Using self-report survey measures, survivors of leukemia,
      bladder, or colorectal cancer who were 2-5 years post-diagnosis and received
      follow-up care in the past year (N = 623) provided information about the presence
      of bothersome symptoms, symptom-related information needs, adequacy of symptom
      related care, and their physical and mental HRQOL. Multivariable statistical
      analyses were conducted to identify correlates of symptom bother, inadequate
      care, and symptom information needs and to examine the association between
      symptom bother and HRQOL. RESULTS: Twenty-eight percent of the 606 respondents
      experienced symptom bother in the past year (46 % of leukemia, 24 % of bladder,
      and 26 % of colorectal cancer survivors). Younger survivors, those of Hispanic
      ethnicity, with low income, those with recurrent cancer, and chemotherapy
      recipients were more likely to report symptom bother (all p < 0.05). Symptom
      bother was associated with lower physical and mental HRQOL (p < 0.001). While 92
      % of survivors with symptoms discussed them with their follow-up care physician,
      52 % of these reported receiving inadequate symptom care. Survivors reporting
      inadequate symptom care were 2.5 times as likely to identify symptom information
      needs compared to those who received adequate care (p < 0.05). CONCLUSIONS: One
      in four cancer survivors report symptoms 2-5 years post-diagnosis, and only half
      of these survivors receive adequate care to address those symptoms. Research that
      refines and tests symptom care interventions for this population is warranted.

PMID- 24018910
TI  - Impact of symptom burden in post-surgical non-small cell lung cancer survivors.
AB  - PURPOSE: Pain, fatigue, dyspnea, and distress are commonly reported cancer
      related symptoms, but few studies have examined the effects of multiple
      concurrent symptoms in longer-term cancer survivors. We examined the impact of
      varying degrees of symptom burden on health-related quality of life (HRQOL) and
      performance status in surgically treated non-small cell lung cancer (NSCLC)
      survivors. METHODS: A sample of 183 NSCLC survivors 1-6 years post-surgical
      treatment completed questionnaires assessing five specific symptoms (pain,
      fatigue, dyspnea, depression, and anxiety), HRQOL, and performance status. The
      number of concurrent clinically significant symptoms was calculated as an
      indicator of symptom burden. RESULTS: Most survivors (79.8 %) had some degree of
      symptom burden, with 30.6 % reporting one clinically significant symptom, 27.9 %
      reporting two symptoms, and 21.3 % reporting three or more symptoms. Physical
      HRQOL significantly decreased as the degree of symptom burden increased, but
      mental HRQOL was only significantly decreased in those with three or more
      symptoms. Receiver-operating characteristic (ROC) curves showed that having
      multiple concurrent symptoms (two or more) was most likely associated with
      limitations in functioning (area under a ROC curve = 0.75, sensitivity = 0.81,
      specificity = 0.54). CONCLUSIONS: Two or more clinically significant symptoms are
      identified as the "tipping point" for showing adverse effects on HRQOL and
      functioning. This highlights the need for incorporating multiple-symptom
      assessment into routine clinical practice. Comprehensive symptom management
      remains an important target of intervention for improved post-treatment HRQOL and
      functioning among lung cancer survivors.

PMID- 24018911
TI  - Clinical significance of SPARC gene expression in patients with gastric cancer.
AB  - PURPOSE: Secreted protein acidic and rich in cysteine (SPARC) is one of the first
      known matricellular proteins that modulates interactions between cells and
      extracellular matrix. Recent studies investigated the clinical significance of
      SPARC gene expression in the development, progression, and metastasis of cancer.
      The present study examined the relations of the relative expression of the SPARC
      gene to clinicopathological factors and overall survival in patients with gastric
      cancer. METHODS: We studied surgical specimens of cancer tissue and adjacent
      normal mucosa obtained from 227 patients with previously untreated gastric
      cancer. The relative expression levels of SPARC mRNA in cancer tissue and in
      adjacent normal mucosa were measured by quantitative real-time, reverse
      transcription polymerase chain reaction. RESULTS: The relative expression level
      of the SPARC gene was higher in cancer tissue than in adjacent normal mucosa.
      High expression levels of the SPARC gene were related to serosal invasion (P =
      0.046). Overall survival at 5 years differed significantly between patients with
      high SPARC gene expression and those with low expression (P = 0.006).
      CONCLUSIONS: Overexpression of the SPARC gene may be a useful independent
      predictor of outcomes in patients with gastric cancer.

PMID- 24018912
TI  - Imaging monitored loosening of dense fibrous tissues using high-intensity pulsed
      ultrasound.
AB  - Pulsed high-intensity focused ultrasound (HIFU) is proposed as a new alternative
      treatment for contracture of dense fibrous tissue. It is hypothesized that the
      pulsed-HIFU can release the contracted tissues by attenuating tensile stiffness
      along the fiber axis, and that the stiffness reduction can be quantitatively
      monitored by change of B-mode images. Fresh porcine tendons and ligaments were
      adapted to an ex vivo model and insonated with pulsed-HIFU for durations ranging
      from 5 to 30 min. The pulse length was 91 us with a repetition frequency of 500
      Hz, and the peak rarefactional pressure was 6.36 MPa. The corresponding average
      intensities were kept around 1606 W cm(-2) for ISPPA and 72.3 W cm(-2) for ISPTA.
      B-mode images of the tissues were acquired before and after pulsed-HIFU exposure,
      and the changes in speckle intensity and organization were analyzed. The tensile
      stiffness of the HIFU-exposed tissues along the longitudinal axis was examined
      using a stretching machine. Histology examinations were performed by optical and
      transmission electron microscopy. Pulsed-HIFU exposure significantly decreased
      the tensile stiffness of the ligaments and tendons. The intensity and
      organization of tissue speckles in the exposed region were also decreased. The
      speckle changes correlated well with the degree of stiffness alteration.
      Histology examinations revealed that pulsed-HIFU exposure probably damages
      tissues via a cavitation-mediated mechanism. Our results suggest that pulsed-HIFU
      with a low duty factor is a promising tool for developing new treatment
      strategies for orthopedic disorders. 

PMID- 24018913
TI  - An in situ formed Pd nanolayer as a bifunctional catalyst for Li-air batteries in
      ambient or simulated air.
AB  - We demonstrate for the first time that a Pd nanolayer, which is in situ formed on
      the Ni foam via the galvanic exchange method, greatly improves the energy output,
      the round-trip efficiency and the cyclability of the aprotic Li-air battery in
      ambient or simulated air. 

PMID- 24018915
TI  - [Learning success of students in surgery with a multimedia-based manual. A
      prospective randomized trial].
AB  - BACKGROUND: Teaching surgery to students means covering two main learning fields:
      theoretical knowledge and practical skills. The objective of this study was to
      compare a multimedia-based surgical procedure manual to a text-based one in a
      student population. METHODS: This randomized controlled trial in a pre-post
      retention test design was conducted online with the participation of 101 medical
      students. Subjects studied the performance of a laparoscopic cholecystectomy
      either in a multimedia-based (MMG) or text-based (TG) presentation. The post-test
      surveyed the knowledge gain and 3 months later a retention test assessed the
      sustainability of that knowledge. RESULTS: The study showed a significant
      knowledge gain in the intragroup comparison. Regarding the procedural knowledge,
      the MMG scored significantly higher in Deltapost-test with 3.84 (MMG) vs 2.98
      (TG) correct answers (p = 0.040). This finding was confirmed in the retention
      test. The MMG (7.17) scored overall significantly higher than the TG (6.41) with
      correct answers (p = 0.028). CONCLUSIONS: Multimedia-based learning can be
      regarded as an alternative to text-based learning. Students learn factual
      knowledge equally well with both devices but the MMG scored higher in procedural
      and more complex knowledge.

PMID- 24018914
TI  - Racial disparities in short sleep duration by occupation and industry.
AB  - Short sleep duration, which is associated with increased morbidity and mortality,
      has been shown to vary by occupation and industry, but few studies have
      investigated differences between black and white populations. By using data from
      a nationally representative sample of US adult short sleepers (n = 41,088) in the
      National Health Interview Survey in 2004-2011, we estimated prevalence ratios for
      short sleep duration in blacks compared with whites for each of 8 industry
      categories by using adjusted Poisson regression models with robust variance.
      Participants' mean age was 47 years; 50% were women and 13% were black. Blacks
      were more likely to report short sleep duration than whites (37% vs. 28%), and
      the black-white disparity was widest among those who held professional
      occupations. Adjusted short sleep duration was more prevalent in blacks than
      whites in the following industry categories: finance/information/real estate
      (prevalence ratio (PR) = 1.44, 95% confidence interval (CI): 1.30, 1.59);
      professional/administrative/management (PR = 1.30, 95% CI: 1.18, 1.44);
      educational services (PR = 1.39, 95% CI: 1.25, 1.54); public
      administration/arts/other services (PR = 1.30, 95% CI: 1.21, 1.41); health
      care/social assistance (PR = 1.23, 95% CI: 1.14, 1.32); and
      manufacturing/construction (PR = 1.14, 95% CI: 1.07, 1.20). Short sleep generally
      increased with increasing professional responsibility within a given industry
      among blacks but decreased with increasing professional roles among whites. Our
      results suggest the need for further investigation of racial/ethnic differences
      in the work-sleep relationship.

PMID- 24018916
TI  - [Professionalization of surgical education in the daily clinical routine.
      Training concept of the Surgical Working Group for Teaching of the German Society
      of Surgery].
AB  - BACKGROUND: For competency-oriented teaching in surgery a comprehensive medical
      educational training and professionalization of clinical teachers is essential.
      The Surgical Working Group for Teaching has therefore set itself the task of
      developing an appropriate training concept. METHOD: In the first step the core
      group took stock of the most relevant educational barriers in the clinical
      environment. Taking into account these findings a trimodular course was devised
      that addressed both previous knowledge and different clinical functions of the
      faculty as well as modern concepts of competency-based academic teaching.
      RESULTS: The A course is designed for medical teaching of novices with a focus on
      collation of the medical history, clinical examination and teaching of practical
      skills. The B course is devised for experienced clinicians and should qualify
      them for competency-based teaching in complex educational scenarios, such as the
      operating room or ward rounds, while the C course is directed to a group of
      persons entrusted with the organization and administration of clinical teaching.

PMID- 24018918
TI  - Structural variation and the expanding genomic architecture of Parkinson disease.

PMID- 24018919
TI  - Infection prevention and control in residential facilities for pediatric patients
      and their families.

PMID- 24018920
TI  - Obtaining blood cultures by venipuncture versus from central lines: impact on
      blood culture contamination rates and potential effect on central line-associated
      bloodstream infection reporting.
AB  - OBJECTIVE: Reduce the frequency of contaminated blood cultures that meet National
      Healthcare Safety Network definitions for a central line-associated bloodstream
      infection (CLABSI). DESIGN: An observational study. SETTING: A 500-bed university
      affiliated hospital. METHODS: A new blood culture policy discouraged drawing
      blood samples from central lines. Phlebotomists were reeducated regarding aseptic
      technique when obtaining blood samples by venipuncture. The intravenous therapy
      team was taught how to draw blood samples by venipuncture and served as a backup
      when phlebotomists were unable to obtain blood samples. A 2-nurse protocol and a
      special supply kit for obtaining blood samples from catheters were developed.
      Rates of blood culture contamination were monitored by the microbiology
      laboratory. RESULTS: The proportion of blood samples obtained for culture from
      central lines decreased from 10.9% during January-June 2010 to 0.4% during July
      December 2012 (P < .001). The proportion of blood cultures that were contaminated
      decreased from 84 (1.6%) of 5,274 during January-June 2010 to 21 (0.5%) of 4,245
      during January-June 2012 (P < .001). Based on estimated excess hospital costs of
      $3,000 per contaminated blood culture, the reduction in blood culture
      contaminants yielded an estimated annualized savings of $378,000 in 2012 when
      compared to 2010. In mid-2010, 3 (30%) of 10 reported CLABSIs were suspected to
      represent blood culture contamination compared with none of 6 CLABSIs reported
      from mid-November 2010 through June 2012 (P = 0.25). CONCLUSIONS: Multiple
      interventions resulted in a reduction in blood culture contamination rates and
      substantial cost savings to the hospital, and they may have reduced the number of
      reportable CLABSIs.

PMID- 24018921
TI  - Implementing a national program to reduce catheter-associated urinary tract
      infection: a quality improvement collaboration of state hospital associations,
      academic medical centers, professional societies, and governmental agencies.
AB  - Catheter-associated urinary tract infection (CAUTI) represents a significant
      proportion of healthcare-associated infections (HAIs). The US Department of
      Health and Human Services issued a plan to reduce HAIs with a target 25%
      reduction of CAUTI by 2013. Michigan's successful collaborative to reduce
      unnecessary use of urinary catheters and CAUTI was based on a partnership between
      diverse hospitals, the state hospital association (SHA), and academic medical
      centers. Taking the lessons learned from Michigan, we are now spreading this work
      throughout the 50 states. This national spread leverages the expertise of
      different groups and organizations for the unified goal of reducing catheter
      related harm. The key components of the project are (1) centralized coordination
      of the effort and dissemination of information to SHAs and hospitals, (2) data
      collection based on established definitions and approaches, (3) focused guidance
      on the technical practices that will prevent CAUTI, (4) emphasis on understanding
      the socioadaptive aspects (both the general, unit-wide issues and CAUTI-specific
      challenges), and (5) partnering with specialty organizations and governmental
      agencies who have expertise in the relevant subject area. The work may serve in
      the future as a model for other large improvement efforts to address other
      hospital-acquired conditions, such as venous thromboembolism and falls. 

PMID- 24018922
TI  - Impact of change to molecular testing for Clostridium difficile infection on
      healthcare facility-associated incidence rates.
AB  - BACKGROUND: Change from nonmolecular to molecular testing techniques is thought
      to contribute to the increasing trend in incidence of Clostridium difficile
      infection (CDI); however the degree of effect attributed to this versus other
      time-related epidemiologic factors is unclear. METHODS: We compared the relative
      change in incidence rate (IRR) of healthcare facility-associated (HCFA) CDI among
      hospitals in the Duke Infection Control Outreach Network before and after the
      date of switch from nonmolecular tests to polymerase chain reaction (PCR) using
      prospectively collected surveillance data from July 2009 to December 2011. Data
      from 10 hospitals that switched and 22 control hospitals were included.
      Individual hospital estimates were determined using Poisson regression. We used
      an interrupted time series approach to develop a Poisson mixed-effects model.
      Additional regression adjustments were made for clustering and proportion of
      intensive care unit patient-days. The variable for PCR was treated as a fixed
      effect; other modeled variables were random effects. RESULTS: For those hospitals
      that switched to PCR, mean incidence rate of HCFA CDI before the switch was 6.0
      CDIs per 10,000 patient-days compared with 9.6 CDIs per 10,000 patient-days after
      the switch. Estimates of hospital-specific IRR that compared after the switch
      with before the switch ranged from 0.89 (95% confidence interval [CI], 0.32-2.44)
      to 6.91 (95% CI, 1.12-42.54). After adjustment in the mixed-effects model, the
      overall IRR comparing CDI incidence after the switch to before the switch was
      1.56 (95% CI, 1.28-1.90). Time-trend variables did not reach statistical
      significance. CONCLUSION: Hospitals that switched from nonmolecular to molecular
      tests experienced an approximate 56% increase in the rate of HCFA CDI after
      testing change.

PMID- 24018923
TI  - Bed occupancy rates and hospital-acquired Clostridium difficile infection: a
      cohort study.
AB  - BACKGROUND: An emergent strain (ribotype 027) of Clostridium difficile infection
      (CDI) has been implicated in epidemics worldwide. Organizational factors such as
      bed occupancy have been associated with an increased incidence of CDI; however,
      the data are sparse, and the association has not been widely demonstrated. We
      investigated the association of bed occupancy and CDI within a large hospital
      organization in the United Kingdom. OBJECTIVE: To establish whether bed occupancy
      rates are a significant risk factor for CDI in the general ward setting. METHODS:
      A retrospective cohort study was carried out on data from 2006 to 2008.
      Univariate and multivariate Cox regression modeling was used to examine the
      strength and significance of the associations. Variables included patient
      characteristics, antibiotic policy exposure, case mix, and bed occupancy rates.
      RESULTS: A total of 1,589 cases of hospital-acquired CDI were diagnosed (1.7% of
      admissions), with an overall infection rate of 2.16 per 1,000 patient-days.
      Median bed occupancy was 93.3% (interquartile range, 83.3%-100%) Univariate and
      multivariate analyses showed positive and statistically significant associations.
      In the adjusted model, patients on wards with occupancy rates of 80%-89.9% had
      rates of CDI that were 56% higher (hazard ratio, 1.56 [95% confidence interval,
      1.18-2.04]; P < .001) compared with baseline (0%-69.9% occupancy). CDI rates were
      55% higher for patients on wards with maximal bed occupancy (100%). CONCLUSIONS:
      There is strong evidence of an association between high bed occupancy and CDI.
      Without effective interventions at high levels of bed occupancy, the economic
      benefits sought from reducing bed numbers may be negated by the increased risk of
      CDI.

PMID- 24018924
TI  - Impact of antibiotic use during hospitalization on the development of
      gastrointestinal colonization with Escherichia coli with reduced fluoroquinolone
      susceptibility.
AB  - OBJECTIVE: Infections due to fluoroquinolone-resistant Escherichia coli (FQREC)
      are associated with significant morbidity and mortality. Fluoroquinolone
      resistance likely arises at the level of gastrointestinal colonization. The
      objective of this study was to identify risk factors for the development of FQREC
      gastrointestinal tract colonization in hospitalized patients, including the
      impact of antibiotics prescribed during hospitalization. DESIGN: A prospective
      cohort study was conducted from 2002 to 2004 within a university health system.
      METHODS: Hospitalized patients initially colonized with fluoroquinolone
      susceptible E. coli were followed up with serial fecal sampling for new FQREC
      colonization or until hospital discharge or death. A Cox proportional hazards
      regression model was developed to identify risk factors for new FQREC
      colonization, with antibiotic exposure modeled as time-varying covariates.
      RESULTS: Of 395 subjects, 73 (18.5%) became newly colonized with FQREC. Length of
      stay before sampling (hazard ratio [HR], 1.02 [95% confidence interval (CI), 1.1
      1.03]; P = .003) and malignancy (HR, 0.37 [95% CI, 0.21-0.67]; P = .001) were
      significantly associated with the development of FQREC colonization. In addition,
      receipt of a first-generation cephalosporin (HR, 1.19 [95% CI, 1.10-1.29]; P <
      .001) or cefepime (HR, 1.05 [95% CI, 1.00-1.10]; P = .048) during hospitalization
      increased the risk of new FQREC colonization. CONCLUSIONS: The acquisition of
      FQREC in the hospital setting is complex, and antimicrobial stewardship programs
      should take into account patterns of antibiotic use in implementing strategies to
      reduce the development of new FQREC colonization. Future studies are needed to
      identify risk factors for infection in hospitalized patients newly colonized with
      FQREC.

PMID- 24018925
TI  - A systematic literature review and meta-analysis of factors associated with
      methicillin-resistant Staphylococcus aureus colonization at time of hospital or
      intensive care unit admission.
AB  - OBJECTIVE: Screening for methicillin-resistant Staphylococcus aureus (MRSA) in
      high-risk patients is a legislative mandate in 9 US states and has been adopted
      by many hospitals. Definitions of high risk differ among hospitals and state
      laws. A systematic evaluation of factors associated with colonization is lacking.
      We performed a systematic review of the literature to assess factors associated
      with MRSA colonization at hospital admission. DESIGN: We searched MEDLINE from
      1966 to 2012 for articles comparing MRSA colonized and noncolonized patients on
      hospital or intensive care unit (ICU) admission. Data were extracted using a
      standardized instrument. Meta-analyses were performed to identify factors
      associated with MRSA colonization. RESULTS: We reviewed 4,381 abstracts; 29
      articles met inclusion criteria (n = 76,913 patients). MRSA colonization at
      hospital admission was associated with recent prior hospitalization (odds ratio
      [OR], 2.4 [95% confidence interval (CI), 1.3-4.7]; P < .01), nursing home
      exposure (OR, 3.8 [95% CI, 2.3-6.3]; P < .01), and history of exposure to
      healthcare-associated pathogens (MRSA carriage: OR, 8.0 [95% CI, 4.2-15.1];
      Clostridium difficile infection: OR, 3.4 [95% CI, 2.2-5.3]; vancomycin-resistant
      Enterococci carriage: OR, 3.1 [95% CI, 2.5-4.0]; P < .01 for all). Select
      comorbidities were associated with MRSA colonization (congestive heart failure,
      diabetes, pulmonary disease, immunosuppression, and renal failure; P < .01 for
      all), while others were not (human immunodeficiency virus, cirrhosis, and
      malignancy). ICU admission was not associated with an increased risk of MRSA
      colonization (OR, 1.1 [95% CI, 0.6-1.8]; P = .87). CONCLUSIONS: MRSA colonization
      on hospital admission was associated with healthcare contact, previous healthcare
      associated pathogens, and select comorbid conditions. ICU admission was not
      associated with MRSA colonization, although this is commonly used in state
      mandates for MRSA screening. Infection prevention programs utilizing targeted
      MRSA screening may consider our results to define patients likely to have MRSA
      colonization.

PMID- 24018926
TI  - Effects of contact precautions on patient perception of care and satisfaction: a
      prospective cohort study.
AB  - OBJECTIVE: Contact precautions decrease healthcare worker-patient contact and may
      impact patient satisfaction. To determine the association between contact
      precautions and patient satisfaction, we used a standardized interview for
      perceived issues with care. DESIGN: Prospective cohort study of inpatients,
      evaluated at admission and on hospital days 3, 7, and 14 (until discharged). At
      each point, patients underwent a standardized interview to identify perceived
      problems with care. After discharge, the standardized interview and Hospital
      Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey were
      administered by telephone. Responses were recorded, transcribed, and coded by 2
      physician reviewers. PARTICIPANTS: A total of 528 medical or surgical patients
      not admitted to the intensive care unit. RESULTS: A total of 528 patients were
      included in the primary analysis, of whom 104 (20%) perceived some issue with
      their care. On multivariable logistic regression, contact precautions were
      independently associated with a greater number of perceived concerns with care
      (odds ratio, 2.05 [95% confidence interval, 1.31-3.21]; P < .01), including poor
      coordination of care (P = .02) and a lack of respect for patient needs and
      preferences (P = .001). Eighty-eight patients were included in the secondary
      analysis of HCAHPS. Patients under contact precautions did not have different
      HCAHPS scores than those not under contact precautions (odds ratio, 1.79 [95%
      confidence interval, 0.64-5.00]; P = .27). CONCLUSIONS: Patients under contact
      precautions were more likely to perceive problems with their care, especially
      poor coordination of care and a lack of respect for patient preferences.

PMID- 24018927
TI  - Time-saving impact of an algorithm to identify potential surgical site
      infections.
AB  - OBJECTIVE: To develop and validate a partially automated algorithm to identify
      surgical site infections (SSIs) using commonly available electronic data to
      reduce manual chart review. DESIGN: Retrospective cohort study of patients
      undergoing specific surgical procedures over a 4-year period from 2007 through
      2010 (algorithm development cohort) or over a 3-month period from January 2011
      through March 2011 (algorithm validation cohort). SETTING: A single academic
      safety-net hospital in a major metropolitan area. PATIENTS: Patients undergoing
      at least 1 included surgical procedure during the study period. METHODS:
      Procedures were identified in the National Healthcare Safety Network; SSIs were
      identified by manual chart review. Commonly available electronic data, including
      microbiologic, laboratory, and administrative data, were identified via a
      clinical data warehouse. Algorithms using combinations of these electronic
      variables were constructed and assessed for their ability to identify SSIs and
      reduce chart review. RESULTS: The most efficient algorithm identified in the
      development cohort combined microbiologic data with postoperative procedure and
      diagnosis codes. This algorithm resulted in 100% sensitivity and 85% specificity.
      Time savings from the algorithm was almost 600 person-hours of chart review. The
      algorithm demonstrated similar sensitivity on application to the validation
      cohort. CONCLUSIONS: A partially automated algorithm to identify potential SSIs
      was highly sensitive and dramatically reduced the amount of manual chart review
      required of infection control personnel during SSI surveillance.

PMID- 24018928
TI  - Applying mindful evidence-based practice at the bedside: using catheter
      associated urinary tract infection as a model.
AB  - We introduce a mindful evidence-based practice model to operationalize
      mindfulness to improve bedside infection prevention practices. Using catheter
      associated urinary tract infection prevention as an example, we illustrate how
      clinicians can be more mindful about appropriate catheter indications and timely
      catheter removal. 

PMID- 24018929
TI  - Behavioral intention of physician trainees and medical students to practice hand
      hygiene.
AB  - Physician trainees were surveyed to assess intention to perform hand hygiene
      (HH). Compared with preclinical medical students (MS), clinical MS and residents
      reported less confidence that HH prevents carrying home microorganisms (P = .006,
      P = .003) or protects oneself from antibiotic-resistant microorganisms (P = .01,
      P = .006). Clinical trainees may need targeted interventions focusing on
      intention to perform HH.

PMID- 24018930
TI  - Does organic material on hospital surfaces reduce the effectiveness of
      hypochlorite and UV radiation for disinfection of Clostridium difficile?
AB  - An organic load of 5%-10% fetal calf serum significantly reduced hypochlorite and
      UV radiation killing of Clostridium difficile spores, but organic material
      collected from hospital surfaces did not affect hypochlorite and only modestly
      affected UV killing of spores. Hypochlorite reduced aerobic microorganisms on
      unclean surfaces with no wiping. 

PMID- 24018931
TI  - Additive effect of Enterococcus faecium on Enterococcal bloodstream infections: a
      14-year study in a Swiss tertiary hospital.
AB  - We investigated whether an increase in enterococcal bloodstream infections (BSIs)
      depends on the emergence of Enterococcus faecium in an area with low vancomycin
      resistant enterococci prevalence. From 1999 to 2012, a linear increase in E.
      faecium BSI rates (0.009 per 1,000 patient-days per year; P < .001) was noted.
      Enterococcus faecalis BSI rates remained stable.

PMID- 24018932
TI  - Downstream impact of urine cultures ordered without indication at two acute care
      teaching hospitals.

PMID- 24018933
TI  - Healthcare epidemiology practicum rotation for postgraduate physician trainees in
      medicine-infectious diseases.

PMID- 24018934
TI  - Stick and tell: a survey of emergency medicine residents and needlestick
      exposures.

PMID- 24018935
TI  - Patients under contact precautions have an increased risk of injuries and
      medication errors: a retrospective cohort study.

PMID- 24018936
TI  - Outbreak of Escherichia coli infections associated with a contaminated
      transesophageal echocardiography probe.

PMID- 24018937
TI  - Annual fluctuation in the rate of resistant bacteria isolated as an indicator in
      the control of hospital-acquired infections.

PMID- 24018938
TI  - Is methicillin-resistant Staphylococcus aureus colonization changing? A study of
      academic health center daycare facilities.

PMID- 24018939
TI  - Hand hygiene championship: a direct observational study.

PMID- 24018940
TI  - High rate of completion of preventive therapy for latent tuberculosis infection
      among asylum seekers in a Swiss Canton.
AB  - BACKGROUND: Preventive treatment may avoid future cases of tuberculosis among
      asylum seekers. The effectiveness of preventive treatment depends in large part
      on treatment completion. METHODS: In a prospective cohort study, asylum seekers
      of two of the Swiss Canton Vaud migration centres were screened with the
      Interferon Gamma Release Assay (IGRA). Those with a positive IGRA were referred
      for medical examination. Individuals with active or past tuberculosis were
      excluded. Preventive treatment was offered to all participants with positive IGRA
      but without active tuberculosis. The adherence was assessed during monthly follow
      up. RESULTS: From a population of 393 adult migrants, 98 (24.9%) had a positive
      IGRA. Eleven did not attend the initial medical assessment. Of the 87 examined,
      eight presented with pulmonary disease (five of them received a full course of
      antituberculous therapy), two had a history of prior tuberculosis treatment and
      two had contraindications to treatment. Preventive treatment was offered to 75
      individuals (4 months rifampicin in 74 and 9 months isoniazid in one), of whom 60
      (80%) completed the treatment. CONCLUSIONS: The vulnerability and the volatility
      of this population make screening and observance of treatment difficult. It seems
      possible to obtain a high rate of completion using a short course of treatment in
      a closely monitored population living in stable housing conditions.

PMID- 24018941
TI  - Redesigning process flow to provide safe, reliable care during critical
      transitions: an interdisciplinary pilot project.

PMID- 24018942
TI  - Medical ICU admissions during weekday rounds are not associated with mortality: a
      single-center analysis.
AB  - This study investigated whether intensive care unit (ICU) admissions to the
      research team's tertiary care academic hospital during morning rounds was
      associated with increased mortality. Discharge data were analyzed on 1912
      patients admitted to the ICUs between July 2007 and June 2011. Measures included
      discharge disposition, time of admission to the ICU, source of admission, and
      expected mortality score. Descriptive statistics were generated to examine the
      proportion of subjects who died based on admission time to the ICU, and Pearson's
      chi(2) test was used to test the null hypothesis that mortality rates for
      admissions during rounds and those at other times of the day would be similar. No
      difference in mortality was detected between admissions during rounds and all
      other times, whether analyzed using a bivariate (P = .55) or multivariable (P =
      .78) analysis. In this study, mortality was associated with severity of illness
      and not associated with admission during morning rounds. 

PMID- 24018943
TI  - Pharmacologically triggered hydrogel for scheduling hepatitis B vaccine
      administration.
AB  - The simplification of current vaccine administration regimes is of crucial
      interest in order to further sustain and expand the high impact of vaccines for
      public health. Most vaccines including the vaccine against hepatitis B need
      several doses to achieve protective immunization. In order to reduce the amount
      of repetitive injections, depot-based approaches represent a promising strategy.
      We present the application of novobiocin-sensitive biohybrid hydrogels as a depot
      for the pharmacologically controlled release of a vaccine against hepatitis B.
      Upon subcutaneous implantation of the vaccine depot into mice, we were able to
      release the vaccine by the oral administration of the stimulus molecule
      novobiocin resulting in successful immunization of the mice. This material-based
      vaccination regime holds high promises to replace classical vaccine injections
      conducted by medical personnel by the simple oral uptake of the stimulus thereby
      solving a major obstacle in increasing hepatitis B vaccination coverage. 

PMID- 24018944
TI  - Changes in physical fitness and sports participation among children with
      different levels of motor competence: a 2-year longitudinal study.
AB  - The goal of this study was to investigate differences in physical fitness and
      sports participation over 2 years in children with relatively high, average, and
      low motor competence. Physical fitness and gross motor coordination of 501
      children between 6-10 years were measured at baseline and baseline+2 years. The
      sample compromised 2 age cohorts: 6.00-7.99 and 8.00-9.99 years. An age and sex
      specific motor quotient at baseline testing was used to subdivide these children
      into low (MQ < P33), average (P33 <= MQ < P66) and high (MQ >= P66) motor
      competence groups. Measures of sports participation were obtained through a
      physical activity questionnaire in 278 of the same children. Repeated Measures
      MANCOVA and two separate ANOVAs were used to analyze differences in changes in
      physical fitness and measures of sports participation respectively. Children with
      high motor competence scored better on physical fitness tests and participated in
      sports more often. Since physical fitness levels between groups changed similarly
      over time, low motor competent children might be at risk for being less
      physically fit throughout their life. Furthermore, since low motor competent
      children participate less in sports, they have fewer opportunities of developing
      motor abilities and physical fitness and this may further prevent them from
      catching up with their peers with an average or high motor competence. 

PMID- 24018945
TI  - Electrotonic suppression of early afterdepolarizations in the neonatal rat
      ventricular myocyte monolayer.
AB  - Pathologies that result in early afterdepolarizations (EADs) are a known trigger
      for tachyarrhythmias, but the conditions that cause surrounding tissue to conduct
      or suppress EADs are poorly understood. Here we introduce a cell culture model of
      EAD propagation consisting of monolayers of cultured neonatal rat ventricular
      myocytes treated with anthopleurin-A (AP-A). AP-A-treated monolayers display a
      cycle length dependent prolongation of action potential duration (245 ms
      untreated, vs. 610 ms at 1 Hz and 1200 ms at 0.5 Hz for AP-A-treated monolayers).
      In contrast, isolated single cells treated with AP-A develop prominent irregular
      oscillations with a frequency of 2.5 Hz, and a variable prolongation of the
      action potential duration of up to several seconds. To investigate whether
      electrotonic interactions between coupled cells modulates EAD formation, cell
      connectivity was reduced by RNA silencing gap junction Cx43. In contrast to well
      connected monolayers, gap junction silenced monolayers display bradycardia
      dependent plateau oscillations consistent with EADs. Further, simulations of a
      cell displaying EADs electrically connected to a cell with normal action
      potentials show a coupling strength-dependent suppression of EADs consistent with
      the experimental results. These results suggest that electrotonic effects may
      play a critical role in EAD-mediated arrhythmogenesis.

PMID- 24018946
TI  - Blood pressure and the contractility of a human leg muscle.
AB  - These studies investigate the relationships between perfusion pressure, force
      output and pressor responses for the contracting human tibialis anterior muscle.
      Eight healthy adults were studied. Changing the height of tibialis anterior
      relative to the heart was used to control local perfusion pressure. Electrically
      stimulated tetanic force output was highly sensitive to physiological variations
      in perfusion pressure showing a proportionate change in force output of 6.5% per
      10 mmHg. This perfusion-dependent change in contractility begins within seconds
      and is reversible with a 53 s time constant, demonstrating a steady-state
      equilibrium between contractility and perfusion pressure. These stimulated
      contractions did not produce significant cardiovascular responses, indicating
      that the muscle pressor response does not play a major role in cardiovascular
      regulation at these workloads. Voluntary contractions at forces that would
      require constant motor drive if perfusion pressure had remained constant
      generated a central pressor response when perfusion pressure was lowered. This is
      consistent with a larger cortical drive being required to compensate for the lost
      contractility with lower perfusion pressure. The relationship between
      contractility and perfusion for this large postural muscle was not different from
      that of a small hand muscle (adductor pollicis) and it responded similarly to
      passive peripheral and active central changes in arterial pressure, but extended
      over a wider operating range of pressures. If we consider that, in a goal
      oriented motor task, muscle contractility determines central motor output and the
      central pressor response, these results indicate that muscle would fatigue twice
      as fast without a pressor response. From its extent, timing and reversibility we
      propose a testable hypothesis that this change in contractility arises through
      contraction- and perfusion-dependent changes in interstitial K(+) concentration.

PMID- 24018947
TI  - Calcium signalling of human pluripotent stem cell-derived cardiomyocytes.
AB  - Loss of cardiomyocytes (CMs), which lack the innate ability to regenerate, due to
      ageing or pathophysiological conditions (e.g. myocardial infarction or MI) is
      generally considered irreversible, and can lead to conditions from cardiac
      arrhythmias to heart failure. Human (h) pluripotent stem cells (PSCs), including
      embryonic stem cells (ESC) and induced pluripotent stem cells (iPSCs), can self
      renew while maintaining their pluripotency to differentiate into all cell types,
      including CMs. Therefore, hPSCs provide a potential unlimited ex vivo source of
      human CMs for disease modelling, drug discovery, cardiotoxicity screening and
      cell-based heart therapies. As a fundamental property of working CMs, Ca(2+)
      signalling and its role in excitation-contraction coupling are well described.
      However, the biology of these processes in hPSC-CMs is just becoming understood.
      Here we review what is known about the immature Ca(2+)-handling properties of
      hPSC-CMs, at the levels of global transients and sparks, and the underlying
      molecular basis in relation to the development of various in vitro approaches to
      drive their maturation.

PMID- 24018948
TI  - Correlation of cellular expression with function of NO-sensitive guanylyl cyclase
      in the murine lower urinary tract.
AB  - The action of nitric oxide (NO) to stimulate NO-sensitive guanylyl cyclase (NO
      GC), followed by production of cGMP, and eventually to cause smooth muscle
      relaxation is well known. In the lower urinary tract (LUT), in contrast to the
      cardiovascular system and the gastrointestinal tract, specific localization in
      combination with function of NO-GC has not been investigated to date.
      Consequently, little is known about the mechanisms regulating relaxation of the
      lower urinary tract in general and the role of NO-GC-expressing cells in
      particular. To study the distribution and function of NO-GC in the murine lower
      urinary tract, we used internal urethral sphincter and bladder detrusor from
      global (GCKO) and smooth muscle cell-specific (SM-GCKO) NO-GC knock-out mice for
      immunohistochemical analyses and organ bath experiments. In urethral sphincter,
      NO-GC-positive immunofluorescence was confined to smooth muscle cells (SMCs).
      Deletion of NO-GC in SMCs abolished NO-induced relaxation. In bladder detrusor,
      exposure to NO did not cause relaxation although immunohistochemistry uncovered
      the existence of NO-GC in the tissue. In contrast to the urethral sphincter,
      expression of NO-GC in bladder detrusor was limited to platelet-derived growth
      factor receptor alpha (PDGFRalpha)-positive interstitial cells. In conclusion, NO
      GC found in SMCs of the urethral sphincter mediates NO-induced relaxation;
      bladder detrusor is unique as NO-GC is not expressed in SMCs and, thus, NO does
      not induce relaxation. Nevertheless, NO-GC expression was found in PDGFRalpha
      positive interstitial cells of the murine bladder with an as yet unknown
      function. Further investigation is needed to clarify the role of NO-GC in the
      detrusor.

PMID- 24018949
TI  - Differential patterns of replacement and reactive fibrosis in pressure and volume
      overload are related to the propensity for ischaemia and involve resistin.
AB  - Pathological left ventricle (LV) hypertrophy (LVH) results in reactive and
      replacement fibrosis. Volume overload LVH (VOH) is less profibrotic than pressure
      overload LVH (POH). Studies attribute subendocardial fibrosis in POH to
      ischaemia, and reduced fibrosis in VOH to collagen degradation favouring
      dilatation. However, the mechanical origin of the relative lack of fibrosis in
      VOH is incompletely understood. We hypothesized that reduced ischaemia propensity
      in VOH compared to POH accounted for the reduced replacement fibrosis, along with
      reduced reactive fibrosis. Rats with POH (ascending aortic banding) evolved into
      either compensated-concentric POH (POH-CLVH) or dilated cardiomyopathy (POH-DCM);
      they were compared to VOH (aorta-caval fistula). We quantified LV fibrosis,
      structural and haemodynamic factors of ischaemia propensity, and the activation
      of profibrotic pathways. Fibrosis in POH-DCM was severe, subendocardial and
      subepicardial, in contrast with subendocardial fibrosis in POH-CLVH and nearly no
      fibrosis in VOH. The propensity for ischaemia was more important in POH versus
      VOH, explaining different patterns of replacement fibrosis. LV collagen synthesis
      and maturation, and matrix metalloproteinase-2 expression, were more important in
      POH. The angiotensin II-transforming growth-factor beta axis was enhanced in POH,
      and connective tissue growth factor (CTGF) was overexpressed in all types of LVH.
      LV resistin expression was markedly elevated in POH, mildly elevated in VOH and
      independently reflected chronic ischaemic injury after myocardial infarction. In
      vitro, resistin is induced by angiotensin II and induces CTGF in cardiomyocytes.
      Based on these findings, we conclude that a reduced ischaemia propensity and
      attenuated upstream reactive fibrotic pathways account for the attenuated
      fibrosis in VOH versus POH.

PMID- 24018950
TI  - Molecular transport machinery involved in orchestrating luminal acid-induced
      duodenal bicarbonate secretion in vivo.
AB  - The duodenal villus brush border membrane expresses several ion transporters
      and/or channels, including the solute carrier 26 anion transporters Slc26a3 (DRA)
      and Slc26a6 (PAT-1), the Na(+)/H(+) exchanger isoform 3 (NHE3), as well as the
      anion channels cystic fibrosis transmembrane conductance regulator (CFTR) and
      Slc26a9. Using genetically engineered mouse models lacking Scl26a3, Slc26a6,
      Slc26a9 or Slc9a3 (NHE3), the study was carried out to assess the role of these
      transporters in mediating the protective duodenal bicarbonate secretory response
      (DBS-R) to luminal acid; and to compare it to their role in DBS-R elicited by the
      adenylyl cyclase agonist forskolin. While basal DBS was reduced in the absence of
      any of the three Slc26 isoforms, the DBS-R to forskolin was not altered. In
      contrast, the DBS-R to a 5 min exposure to luminal acid (pH 2.5) was strongly
      reduced in the absence of Slc26a3 or Slc26a9, but not Slc26a6. CFTR inhibitor
      [CFTR(Inh)-172] reduced the first phase of the acid-induced DBS-R, while NHE3
      inhibition (or knockout) abolished the sustained phase of the DBS-R. Luminal acid
      exposure resulted in the activation of multiple intracellular signalling
      pathways, including SPAK, AKT and p38 phosphorylation. It induced a biphasic
      trafficking of NHE3, first rapidly into the brush border membrane, followed by
      endocytosis in the later stage. We conclude that the long-lasting DBS-R to
      luminal acid exposure activates multiple duodenocyte signalling pathways and
      involves changes in trafficking and/or activity of CFTR, Slc26 isoforms Slc26a3
      and Slc26a9, and NHE3.

PMID- 24018952
TI  - Molecular ferroelectrics: where electronics meet biology.
AB  - In the last several years, we have witnessed significant advances in molecular
      ferroelectrics, with the ferroelectric properties of molecular crystals
      approaching those of barium titanate. In addition, ferroelectricity has been
      observed in biological systems, filling an important missing link in bioelectric
      phenomena. In this perspective, we will present short historical notes on
      ferroelectrics, followed by an overview of the fundamentals of ferroelectricity.
      The latest developments in molecular ferroelectrics and biological
      ferroelectricity will then be highlighted, and their implications and potential
      applications will be discussed. We close by noting molecular ferroelectric as an
      exciting frontier between electronics and biology, and a number of challenges
      ahead are also described. 

PMID- 24018951
TI  - Reciprocal regulation of inhibitory synaptic transmission by nicotinic and
      muscarinic receptors in rat nucleus accumbens shell.
AB  - Medium spiny neurones (MSNs) in the nucleus accumbens (NAc) are the principal
      neurones whose activities are regulated by GABAergic inputs from MSNs and fast
      spiking interneurones (FSNs). Cholinergic interneurones play important roles in
      the regulation of activity in MSNs; however, how acetylcholine modulates
      inhibitory synaptic transmission from MSNs/FSNs to MSNs remains unknown. We
      performed paired whole-cell patch-clamp recordings from MSNs and FSNs in rat NAc
      shell slice preparations and examined cholinergic effects on unitary inhibitory
      postsynaptic currents (uIPSCs). Carbachol (1 MUM) suppressed uIPSC amplitude by
      58.3 +/- 8.0% in MSN->MSN connections, accompanied by increases in paired-pulse
      ratio and failure rate, suggesting that acetylcholine reduces the probability of
      GABA release from the synaptic terminals of MSNs. Carbachol-induced uIPSC
      suppression was antagonised by 100 MUM atropine, and was mimicked by pilocarpine
      (1 MUM) and acetylcholine (1 MUM) but not nicotine (1 MUM). Application of AM251
      slightly reduced carbachol-induced uIPSC suppression (30.8 +/- 8.9%), suggesting
      an involvement of endocannabinoid signalling in muscarinic suppression of uIPSCs.
      In contrast, FSN->MSN connections showed that pilocarpine had little effect on
      the uIPSC amplitude, whereas both nicotine and acetylcholine facilitated uIPSC
      amplitude, with decreases in failure rate and paired-pulse ratio, suggesting that
      nicotine-induced uIPSC facilitation is mediated by presynaptic mechanisms.
      Miniature IPSC recordings support these hypotheses of presynaptic cholinergic
      mechanisms. These results suggest a differential role for muscarinic and
      nicotinic receptors in GABA release, which depends on presynaptic neuronal
      subtypes in the NAc shell.

PMID- 24018953
TI  - Human-computer interaction based on hand gestures using RGB-D sensors.
AB  - In this paper we present a new method for hand gesture recognition based on an
      RGB-D sensor. The proposed approach takes advantage of depth information to cope
      with the most common problems of traditional video-based hand segmentation
      methods: cluttered backgrounds and occlusions. The algorithm also uses colour and
      semantic information to accurately identify any number of hands present in the
      image. Ten different static hand gestures are recognised, including all different
      combinations of spread fingers. Additionally, movements of an open hand are
      followed and 6 dynamic gestures are identified. The main advantage of our
      approach is the freedom of the user's hands to be at any position of the image
      without the need of wearing any specific clothing or additional devices. Besides,
      the whole method can be executed without any initial training or calibration.
      Experiments carried out with different users and in different environments prove
      the accuracy and robustness of the method which, additionally, can be run in real
      time. 

PMID- 24018954
TI  - Theoretical analysis of interferometer wave front tilt and fringe radiant flux on
      a rectangular photodetector.
AB  - This paper is a theoretical analysis of mirror tilt in a Michelson interferometer
      and its effect on the radiant flux over the active area of a rectangular
      photodetector or image sensor pixel. It is relevant to sensor applications using
      homodyne interferometry where these opto-electronic devices are employed for
      partial fringe counting. Formulas are derived for radiant flux across the
      detector for variable location within the fringe pattern and with varying wave
      front angle. The results indicate that the flux is a damped sine function of the
      wave front angle, with a decay constant of the ratio of wavelength to detector
      width. The modulation amplitude of the dynamic fringe pattern reduces to zero at
      wave front angles that are an integer multiple of this ratio and the results show
      that the polarity of the radiant flux changes exclusively at these multiples.
      Varying tilt angle causes radiant flux oscillations under an envelope curve, the
      frequency of which is dependent on the location of the detector with the fringe
      pattern. It is also shown that a fringe count of zero can be obtained for
      specific photodetector locations and wave front angles where the combined effect
      of fringe contraction and fringe tilt can have equal and opposite effects. Fringe
      tilt as a result of a wave front angle of 0.05 degrees  can introduce a phase
      measurement difference of 16 degrees  between a photodetector/pixel located 20 mm
      and one located 100 mm from the optical origin. 

PMID- 24018956
TI  - Extranodal metastasis is a powerful prognostic factor in patients with
      adenocarcinoma of the esophagogastric junction.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study is to estimate the effect of
      extranodal metastasis (EM) on recurrence and survival in patients with
      adenocarcinoma of the esophagogastric junction (AEG) after curative resection.
      METHODS: Clinical data from 284 node-positive AEG patients who underwent curative
      resection were reviewed. Univariate and multivariate analyses were conducted to
      elucidate the effect of EM on recurrence-free survival (RFS) and overall survival
      (OS). RESULTS: EM was detected in 70 (24.6%) of the 284 cases. It had a
      significant correlation with tumor size, Lauren type, histopathological grading,
      depth of tumor invasion, number of metastatic nodes, lymph node ratio, and TNM
      stage. The 5-year RFS and OS rates were 22.2% and 24.3%, respectively. Patients
      with EM had a significantly decreased RFS (16 vs. 36 months, P < 0.001) and OS
      (23 vs. 41 months, P < 0.001) compared with those without EM. Multivariate
      analyses identified EM as an independent prognostic factor (P = 0.003 and 0.001,
      respectively). CONCLUSION: The presence of EM increases recurrence probability
      and reduces OS probability of AEG patients with lymph node metastasis. EM is a
      powerful prognostic factor reflecting a particularly aggressive biological
      behavior. Better understanding of EM status can help clinicians with regard to
      treatment decision and prognosis evaluation.

PMID- 24018957
TI  - Effects of a pressure release on virus retention with the Ultipor DV20 membrane.
AB  - Recent data have shown that a temporary release in the transmembrane pressure can
      cause a significant increase in virus transmission through a number of commercial
      virus filters. The objective of this work was to study the effect of a pressure
      release on retention of the bacteriophage PhiX174 by the Ultipor DV20 membrane,
      with phage capture within the membrane visualized by confocal microscopy. Phage
      challenge tests showed a significant transient increase in phage transmission
      (typically by an order of magnitude) immediately after a pressure release. This
      transient increase was not due to any damage to the filter or to the presence of
      a back-flow (from permeate to feed). Confocal images demonstrated that the
      pressure release caused the migration of previously captured bacteriophage
      further into the depth of the filter. Data were analyzed using a modified
      internal polarization model, with the results providing important insights into
      the factors controlling virus retention during virus filtration.

PMID- 24018955
TI  - Application of a novel tool for diagnosing bile acid diarrhoea.
AB  - Bile acid diarrhoea (BAD) is a common disease that requires expensive imaging to
      diagnose. We have tested the efficacy of a new method to identify BAD, based on
      the detection of differences in volatile organic compounds (VOC) in urine
      headspace of BAD vs. ulcerative colitis and healthy controls. A total of 110
      patients were recruited; 23 with BAD, 42 with ulcerative colitis (UC) and 45
      controls. Patients with BAD also received standard imaging (Se75HCAT) for
      confirmation. Urine samples were collected and the headspace analysed using an
      AlphaMOS Fox 4000 electronic nose in combination with an Owlstone Lonestar Field
      Asymmetric Ion Mobility Spectrometer (FAIMS). A subset was also tested by gas
      chromatography, mass spectrometry (GCMS). Linear Discriminant Analysis (LDA) was
      used to explore both the electronic nose and FAIMS data. LDA showed statistical
      differences between the groups, with reclassification success rates (using an n-1
      approach) at typically 83%. GCMS experiments confirmed these results and showed
      that patients with BAD had two chemical compounds, 2-propanol and acetamide, that
      were either not present or were in much reduced quantities in the ulcerative
      colitis and control samples. We believe that this work may lead to a new tool to
      diagnose BAD, which is cheaper, quicker and easier that current methods. 

PMID- 24018958
TI  - An enhanced mobile-healthcare emergency system based on extended chaotic maps.
AB  - Mobile Healthcare (m-Healthcare) systems, namely smartphone applications of
      pervasive computing that utilize wireless body sensor networks (BSNs), have
      recently been proposed to provide smartphone users with health monitoring
      services and received great attentions. An m-Healthcare system with flaws,
      however, may leak out the smartphone user's personal information and cause
      security, privacy preservation, or user anonymity problems. In 2012, Lu et al.
      proposed a secure and privacy-preserving opportunistic computing (SPOC) framework
      for mobile-Healthcare emergency. The brilliant SPOC framework can
      opportunistically gather resources on the smartphone such as computing power and
      energy to process the computing-intensive personal health information (PHI) in
      case of an m-Healthcare emergency with minimal privacy disclosure. To balance
      between the hazard of PHI privacy disclosure and the necessity of PHI processing
      and transmission in m-Healthcare emergency, in their SPOC framework, Lu et al.
      introduced an efficient user-centric privacy access control system which they
      built on the basis of an attribute-based access control mechanism and a new
      privacy-preserving scalar product computation (PPSPC) technique. However, we
      found out that Lu et al.'s protocol still has some secure flaws such as user
      anonymity and mutual authentication. To fix those problems and further enhance
      the computation efficiency of Lu et al.'s protocol, in this article, the authors
      will present an improved mobile-Healthcare emergency system based on extended
      chaotic maps. The new system is capable of not only providing flawless user
      anonymity and mutual authentication but also reducing the computation cost. 

PMID- 24018959
TI  - Induction of human umbilical Wharton's jelly-derived stem cells toward
      oligodendrocyte phenotype.
AB  - In this study, we examined phenotypic features of human Wharton's jelly
      mesenchymal stem cells-derived oligodendrocytes. We induced human WJMSCs to form
      OLs by signaling molecules including basic fibroblastic growth factor, platelet
      derived growth factor-AA, and triiodothyronine hormone. Differentiated WJMSCs
      showed morphologic characteristics of an OL phenotype. Expression of surface
      markers and genes in oligodendrocyte precursor cells or OLs were analyzed by
      immunocytochemistry staining and real-time polymerase chain reaction,
      respectively. These results suggest that WJMSCs could be programmed to OLs and
      might provide a potential source for cell therapy in neurodegenerative disease. 

PMID- 24018961
TI  - Little to no genetic structure in the ectomycorrhizal basidiomycete Suillus
      spraguei (Syn. S. pictus) across parts of the Northeastern USA.
AB  - Population genetic studies of ectomycorrhizal fungi at scales larger than 100 km
      are still relatively rare with highly variable results. In this study, we
      determined the population genetic structure of the ectomycorrhizal basidiomycete
      Suillus spraguei over distances up to 600 km in northeastern USA forests. S.
      spraguei associates exclusively with five-needled pines and only with white pine
      (Pinus strobus) in the eastern USA. We used six microsatellite loci to assess the
      genetic structure between eight sites sampled in the Adirondack Park of New York
      and seven sites sampled in other forests of New York, Pennsylvania, and
      Massachusetts. Except for one site, little to no genetic differentiation was
      detected in pairwise comparisons of the sites (F ST = 0 to 0.05). Only one site
      was moderately differentiated from most other sites (F ST = 0.02 to 0.15). The
      Mantel test showed no significant correlation between genetic and geographic
      distances (isolation by distance; R (2) = 0.003, P = 0.3). The STRUCTURE analysis
      also supported the presence of a single cluster (K = 1). 

PMID- 24018960
TI  - Loss of fornix white matter volume as a predictor of cognitive impairment in
      cognitively normal elderly individuals.
AB  - IMPORTANCE: Magnetic resonance imaging markers of incipient cognitive decline
      among healthy elderly individuals have become important for both clarifying the
      biological underpinnings of dementia and clinically identifying healthy
      individuals at high risk of cognitive decline. Even though the role of
      hippocampal atrophy is well known in the later stages of decline, the ability of
      fornix-hippocampal markers to predict the earliest clinical deterioration is less
      clear. OBJECTIVES: To examine the involvement of the hippocampus-fornix circuit
      in the very earliest stages of cognitive impairment and to determine whether the
      volumes of fornix white matter and hippocampal gray matter would be useful
      markers for understanding the onset of dementia and for clinical intervention.
      DESIGN: A longitudinal cohort of cognitively normal elderly participants received
      clinical evaluations with T1-weighted magnetic resonance imaging and diffusivity
      scans during repeated visits over an average of 4 years. Regression and Cox
      proportional hazards models were used to analyze the relationships between fornix
      and hippocampal measures and their predictive power for incidence and time of
      conversion from normal to impaired cognition. SETTING: A cohort of community
      recruited elderly individuals at the Alzheimer Disease Center of the University
      of California, Davis. PARTICIPANTS: A total of 102 cognitively normal elderly
      participants, with an average age of 73 years, recruited through community
      outreach using methods designed to enhance ethnic diversity. MAIN OUTCOMES AND
      MEASURES: Our preliminary hypothesis was that fornix white matter volume should
      be a significant predictor of cognitive decline among normal elderly individuals
      and that fornix measures would be associated with gray matter changes in the
      hippocampus. RESULTS: Fornix body volume and axial diffusivity were highly
      significant predictors (P = .02 and .005, respectively) of cognitive decline from
      normal cognition. Hippocampal volume was not significant as a predictor of
      decline but was significantly associated with fornix volume and diffusivity (P =
      .004). CONCLUSIONS AND RELEVANCE: This could be among the first studies
      establishing fornix degeneration as a predictor of incipient cognitive decline
      among healthy elderly individuals. Predictive fornix volume reductions might be
      explained at least in part by clinically silent hippocampus degeneration. The
      importance of this finding is that white matter tract measures may become
      promising candidate biomarkers for identifying incipient cognitive decline in a
      clinical setting, possibly more so than traditional gray matter measures.

PMID- 24018962
TI  - [Methodological deficits in neuroethics: do we need theoretical neuroethics?].
AB  - Current neuroethics can be characterized best as empirical neuroethics: it is
      strongly empirically oriented in that it not only includes empirical findings
      from neuroscience but also searches for applications within neuroscience. This,
      however, neglects the social and political contexts which could be subject to a
      future social neuroethics. In addition, methodological issues need to be
      considered as in theoretical neuroethics. The focus in this article is on two
      such methodological issues: (1) the analysis of the different levels and their
      inferences among each other which is exemplified by the inference of
      consciousness from the otherwise purely neuronal data in patients with vegetative
      state and (2) the problem of linking descriptive and normative concepts in a non
      reductive and non-inferential way for which I suggest the mutual
      contextualization between both concepts. This results in a methodological
      strategy that can be described as contextual fact-norm iterativity.

PMID- 24018963
TI  - [Multiple sclerosis and physical activity: an historical perspective].
AB  - Uncertainties concerning the pathology of multiple sclerosis have in the past led
      to numerous theories about the cause and therapy of the disease. In the last 40
      years technological progress and the use of scientific research methods have
      contributed to a considerably enlarged body of medical and scientific knowledge,
      a process that has not yet come to an end. The attitude towards physical activity
      has also changed tremendously over time. There was a paradigm shift from the fear
      of triggering and aggravating the disease towards therapeutic benefits of
      physical activity and exercise. The first evidence for beneficial effects of
      exercise on symptoms and the course of the disease originated in the 1960s;
      however, a growing scientific interest in the topic was not recognizable until
      the 1990s when the number of exercise studies finally started to increase.
      Nowadays, the positive effects of physical activity and exercise are well
      established; nevertheless, high-quality research reports are still lacking. As a
      consequence there are still many unresolved questions concerning specific
      training effects and recommendations.

PMID- 24018964
TI  - Social influences on the estrous cycle of the captive sun bear (Helarctos
      Malayanus).
AB  - We examined the potential influences of existing social housing arrangements on
      captive sun bear female reproductive cycling. Three social conditions were
      studied: 1.2, 1.1, and 0.2. Fecal hormone metabolites of total estrogens,
      progestins and glucocorticoids were compared between the three social conditions
      and were analyzed along with vaginal cytology data in individuals that
      experienced a change in social condition. Behavioral data were collected on
      females in each of the social conditions and summarized into agonistic,
      affiliative and sexual categories. Results indicated that sun bears are
      spontaneous ovulators, but that the presence of a male does influence hormone
      metabolite concentrations and cytological profiles. Male presence was also
      associated with a greater proportion of females cycling. In most female pairs,
      only one female cycled, typically the younger, subordinate female. The presence
      of a second female appeared to have a suppressive influence on both cycling and
      mating behavior. Agonistic behavior and associated stress may be a mechanism for
      lowering progesterone. In contrast, high estrogen levels were associated with low
      levels of agonistic interactions; thus, reproductive cycle monitoring could
      facilitate social introductions with either sex. Females in 1.2 social groupings
      had significantly higher GC metabolite concentrations and agonistic behavior,
      suggesting that 1.2 social groupings may not be advisable for captive breeding
      programs. Data from the North American historical captive population indicate
      that at most 32% of all sun bear pairs and only 18.5% of females have
      successfully reproduced. Implications of these social and reproductive patterns
      for captive management are discussed.

PMID- 24018965
TI  - Programmable hydrogels for the controlled release of therapeutic nucleic acid
      aptamers via reversible DNA hybridization.
AB  - Reversible DNA hybridization can be used as a new mechanism to control the
      sustained and triggered release of therapeutic oligonucleotides from hydrogels. 

PMID- 24018966
TI  - Ultrasonically induced dynamics of a contrast agent microbubble between two
      parallel elastic walls.
AB  - This work presents the derivation of a Rayleigh-Plesset-like equation that
      describes the radial oscillation of a contrast agent microbubble between two
      elastic walls, assuming that the bubble is attached to one of them. The obtained
      equation is then used in numerical simulations in order to establish how the
      presence of the second wall affects the resonance properties and the scattered
      echo of the contrast microbubble. The effect of encapsulation on the dynamics of
      the microbubble is simulated by the Marmottant shell model which is commonly used
      for the modeling of the dynamics of lipid-shelled contrast agents. Two cases are
      examined. In the first, the mechanical properties of the walls are set to
      correspond to OptiCell chambers which are widely used in experiments on
      microbubble contrast agents. In the second, the properties of the walls
      correspond to walls of blood vessels. It is shown that the presence of the second
      wall increases the resonance frequency of the contrast microbubble and decreases
      the amplitudes of the radial oscillation and the scattered echo of the
      microbubble as compared to the case that the second wall is absent. It is also
      shown that the presence of the second wall can change noticeably the intensity of
      the second harmonic in the spectrum of the scattered pressure. It is demonstrated
      that, depending on the value of the driving frequency, the presence of the second
      wall can either increase or decrease the intensity of the second harmonic as
      compared to its intensity in the case that the second wall is absent. 

PMID- 24018967
TI  - Diversity of halophilic archaea in fermented foods and human intestines and their
      application.
AB  - Archaea are prokaryotic organisms distinct from bacteria in the structural and
      molecular biological sense, and these microorganisms are known to thrive mostly
      at extreme environments. In particular, most studies on halophilic archaea have
      been focused on environmental and ecological researches. However, new species of
      halophilic archaea are being isolated and identified from high salt-fermented
      foods consumed by humans, and it has been found that various types of halophilic
      archaea exist in food products by culture-independent molecular biological
      methods. In addition, even if the numbers are not quite high, DNAs of various
      halophilic archaea are being detected in human intestines and much interest is
      given to their possible roles. This review aims to summarize the types and
      characteristics of halophilic archaea reported to be present in foods and human
      intestines and to discuss their application as well.

PMID- 24018968
TI  - Hfq and ArcA are involved in the stationary phase-dependent activation of
      Salmonella pathogenicity island 1 (SPI1) under shaking culture conditions.
AB  - In Salmonella enterica serovar Typhimurium, many genes encoded within Salmonella
      pathogenicity island 1 (SPI1) are required to induce intestinal/diarrheal
      disease. In this study, we compared the expression of four SPI1 genes (hilA,
      invF, prgH, and sipC) under shaking and standing culture conditions and found
      that the expression of these genes was highest during the transition from the
      exponential to stationary phase under shaking conditions. To identify regulators
      associated with the stationary phase-dependent activation of SPI1, the effects of
      selected regulatory genes, including relA/spoT (ppGpp), luxS, ihfB, hfq, and
      arcA, on the expression of hilA and invF were compared under shaking conditions.
      Mutations in the hfq and arcA genes caused a reduction in hilA and invF
      expression (more than 2-fold) in the early stationary phase only, whereas the
      lack of ppGpp and IHF decreased hilA and invF gene expression during the entire
      stationary phase. We also found that hfq and arcA mutations caused a reduction of
      hilD expression upon entry into the stationary phase under shaking culture
      conditions. Taken together, these results suggest that Hfq and ArcA regulate the
      hilD promoter, causing an accumulation of HilD, which can trigger a stationary
      phase-dependent activation of SPI1 genes under shaking culture conditions. 

PMID- 24018969
TI  - t10,c12 conjugated linoleic acid upregulates hepatic de novo lipogenesis and
      triglyceride synthesis via mTOR pathway activation.
AB  - In mice, supplementation of t10,c12 conjugated linoleic acid (CLA) increases
      liver mass and hepatic steatosis via increasing uptake of fatty acids released
      from adipose tissues. However, the effects of t10,c12 CLA on hepatic lipid
      synthesis and the associated mechanisms are largely unknown. Thus, we tested the
      hypothesis that gut microbiota-producing t10,c12 CLA would induce de novo
      lipogenesis and triglyceride (TG) synthesis in HepG2 cells, promoting lipid
      accumulation. It was found that treatment with t10,c12 CLA (100 micrometer) for
      72 h increased neutral lipid accumulation via enhanced incorporation of acetate,
      palmitate, oleate, and 2- deoxyglucose into TG. Furthermore, treatment with
      t10,c12 CLA led to increased mRNA expression and protein levels of lipogenic
      genes including SREBP1, ACC1, FASN, ELOVL6, GPAT1, and DGAT1, presenting
      potential mechanisms by which CLA may increase lipid deposition. Most strikingly,
      t10,c12 CLA treatment for 3 h increased phosphorylation of mTOR, S6K, and S6.
      Taken together, gut microbiota-producing t10,c12 CLA activates hepatic de novo
      lipogenesis and TG synthesis through activation of the mTOR/SREBP1 pathway, with
      consequent lipid accumulation in HepG2 cells.

PMID- 24018970
TI  - Effects of nutritional and environmental conditions on planktonic growth and
      biofilm formation of Citrobacter werkmanii BF-6.
AB  - Citrobacter sp. is a cause of significant opportunistic nosocomial infection and
      is frequently found in human and animal feces, soil, and sewage water, and even
      in industrial waste or putrefaction. Biofilm formation is an important virulence
      trait of Citrobacter sp. pathogens but the process and characteristics of this
      formation are unclear. Therefore, we employed in vitro assays to study the
      nutritional and environmental parameters that might influence biofilm formation
      of C. werkmanii BF-6 using 96-well microtiter plates. In addition, we detected
      the relative transcript levels of biofilm formation genes by RT-PCR. Our results
      indicated that the capacity of C. werkmanii BF-6 to form biofilms was affected by
      culture temperature, media, time, pH, and the osmotic agents glucose, sucrose,
      NaCl, and KCl. Confocal laser scanning microscopy results illustrated that the
      structure of biofilms and extracellular polysaccharide was influenced by 100 mM
      NaCl or 100 mM KCl. In addition, nine biofilm formation genes (bsmA, bssR, bssS,
      csgD, csgE, csgF, mrkA, mrkB, and mrkE) were found to contribute to planktonic
      and biofilm growth. Our data suggest that biofilm formation by C. werkmanii BF-6
      is affected by nutritional and environmental factors, which could pave the way to
      the prevention and elimination of biofilm formation using proper strategies. 

PMID- 24018971
TI  - Ginsenoside Rb1 is transformed into Rd and Rh2 by Microbacterium
      trichothecenolyticum.
AB  - Ginsenosides are the most important ingredient of ginseng and are known to
      possess many pharmacological and biological effects. Rb1, a major protopanaxadiol
      ginsenoside, is the most abundant ginsenoside in Panax ginseng C.A Meyer and can
      be hydrolyzed into more pharmaceutically potent minor ginsenosides. To identify a
      microorganism that is capable of converting Rb1 into other ginsenosides, we
      screened 12 Microbacterium spp., and M. trichothecenolyticum was identified as a
      likely candidate. M. trichothecenolyticum converted Rb1 into Rd and then into Rh2
      based on TLC and HPLC analyses of reaction products. This biotransformation
      method can be easily applied for mass production of Rd and Rh2 by using Rb1. 

PMID- 24018972
TI  - Novel porphyrinic porous organic frameworks for high performance separation of
      small hydrocarbons.
AB  - A series of Porphyrinic-CTF materials are synthesized under ionothermal condition
      with high surface areas (>3200 m(2)/g) and tunable pore sizes. The ZnP-CTFs
      exhibit high adsorption capacities and selectivity towards C3H8, and C2H6 over
      CH4 as IAST prediction. Furthermore, we explore the utility of ZnP-CTF for gas
      chromatographic separation of the small hydrocarbons mixture based on their
      different van der waals interactions and polarizability. More importantly, the
      fast breakthrough test further proves that the ZnP-CTF-400 and ZnP-CTF-500 can
      separate the small hydrocarbons under kinetic dynamic conditions.

PMID- 24018973
TI  - Prevalence of severely impaired left ventricular ejection fraction after
      reperfused ST-elevation myocardial infarction.
AB  - BACKGROUND: Preventive implantation of an implantable cardioverter defibrillator
      (ICD) early after myocardial infarction failed to demonstrate a survival benefit
      in patients with depressed left ventricular ejection fraction (LVEF). This may be
      explained by early recovery of the LVEF after percutaneous coronary intervention
      (PCI). We sought to determine the incidence of a sustained LVEF <=35% in patients
      with severely depressed LVEF early after a revascularised acute ST-segment
      elevation myocardial infarction (STEMI). METHODS: LVEF was assessed in patients
      with an acute STEMI treated with PCI in two Swiss high-volume centres within 10
      days (in-hospital LVEF) after the STEMI. Those with an in-hospital LVEF <=35%
      were scheduled for follow-up LVEF measurement within 6-8 weeks. RESULTS: A total
      of 330 patients were included (79% male, mean age 63 +/- 12 years). In-hospital
      LVEF measured 3 +/- 3 days after STEMI was <=35% in 32/330 patients (10%, 95%
      confidence interval (CI) 13%-67%). LVEF was available in 31/32 (97%) patients at
      follow-up 53 +/- 19 days after STEMI and improved to >35% in 19 patients (61%,
      95% CI 42%-78%). The incidence of a LVEF <=35% at follow-up was 39% (12/31, 95%
      CI 22%-56%). CONCLUSION: Our data demonstrate that the incidence of severely
      impaired LV function 53 +/- 19 days after a STEMI treated with PCI is low. A
      severely depressed LVEF early after STEMI was present in 10% of all patients.
      Only 39% of these patients had a persistently impaired LVEF during follow-up.
      These findings support an expectant strategy before considering primary
      preventive ICD implantation after STEMI.

PMID- 24018974
TI  - Association between accelerometer-measured physical activity intensities and
      sedentary time in 8- to 10-year-old children.
AB  - This study examines the association between objectively-measured physical
      activity (PA) intensities and sedentary behavior (SED) in a cohort of 532
      children aged 8-10 y. PA and SED were assessed by accelerometer over 7-days.
      Television and computer/video-game use were self-reported. Associations between
      PA intensities and SED variables were assessed by Spearman correlations and
      adjusted multiple linear regression. Higher mean daily moderate-to-vigorous and
      vigorous PA (MVPA, VPA) were negatively associated with mean daily SED (r = -0.47
      and -0.37; p < .001), and positively associated with mean daily total PA (r = .58
      and 0.46; p < .001). MVPA was also positively associated with light PA (LPA; r =
      .26, p < .001). MVPA and VPA were not significantly associated with TV,
      computer/video or total screen time; accelerometer SED was only weakly associated
      with specific SED behaviors. On average, for each additional 10 min daily MVPA,
      children accumulated >14 min less SED, and for each additional 5 min VPA, 11 min
      less SED. Thus, over the course of a week, higher mean daily MVPA may displace
      SED time and is associated with higher total PA over and above the additional
      MVPA, due to concomitant higher levels of LPA. Public health strategies should
      target both MVPA and SED to improve overall PA and health in children. 

PMID- 24018976
TI  - Biomechanical comparison between suture anchor and transtibial pull-out repair
      for posterior medial meniscus root tears.
AB  - BACKGROUND: Posterior medial meniscus root (PMMR) tears have a serious effect on
      knee joint biomechanics. Currently used techniques for refixation of the PMMR
      include the transtibial pull-out repair (TP) and suture anchor repair (SA). These
      techniques have not been compared biomechanically. HYPOTHESIS: The SA technique
      provides superior biomechanical properties compared with the TP technique. STUDY
      DESIGN: Controlled laboratory study. METHODS: A total of 24 fresh-frozen porcine
      tibiae with attached intact medial menisci were used. The specimens were randomly
      assigned to 3 groups (8 specimens each). A standardized PMMR tear was created in
      16 specimens. Refixation of the PMMR was performed by either the TP or SA
      technique. The native PMMR was left intact in 8 specimens. All specimens were
      subjected to cyclic loading followed by load-to-failure testing. Displacement
      after 100, 500, and 1000 cycles; maximum load to failure; stiffness; and
      displacement at failure were recorded. RESULTS: Both repair techniques showed a
      significantly higher displacement during cyclic loading and a significantly lower
      maximum load and stiffness during load-to-failure testing compared with the
      native PMMR (P < .05). The SA technique showed a significantly lower displacement
      after 100, 500, and 1000 cycles (P < .001) and a significantly higher stiffness
      (P = .016) compared with the TP technique. Maximum load did not differ
      significantly between the SA and TP techniques (P = .027, Bonferroni adjustment).
      No significant difference between the 3 groups was observed for displacement at
      failure (P > .05). CONCLUSION: The SA technique provided superior biomechanical
      properties compared with the TP technique. Both repair techniques did not reach
      the strength of the native PMMR. CLINICAL RELEVANCE: The favorable biomechanical
      properties of the SA technique might be beneficial for healing of the repaired
      PMMR and restoration of meniscus function. Because of inferior time zero
      stability compared with the native PMMR, slow rehabilitation is recommended after
      meniscus root repair.

PMID- 24018977
TI  - Ruthenium(II)-catalyzed C-H alkenylations of phenols with removable directing
      groups.
AB  - Cationic ruthenium(II) complexes enabled oxidative alkenylations of phenols
      bearing easily cleavable directing groups. The optimized catalytic system allowed
      twofold C?H bond activations with excellent chemo-, site-, and
      diastereoselectivities. The double C?H functionalization process proceeded
      efficiently in an aerobic fashion under an atmosphere of ambient air. Detailed
      mechanistic studies were performed and provided strong support for an initial
      reversible C?H bond activation by the formation of six-membered ruthenacycles as
      the key intermediates. 

PMID- 24018975
TI  - Tumour angiogenesis regulation by the miR-200 family.
AB  - The miR-200 family is well known to inhibit the epithelial-mesenchymal
      transition, suggesting it may therapeutically inhibit metastatic biology.
      However, conflicting reports regarding the role of miR-200 in suppressing or
      promoting metastasis in different cancer types have left unanswered questions.
      Here we demonstrate a difference in clinical outcome based on miR-200's role in
      blocking tumour angiogenesis. We demonstrate that miR-200 inhibits angiogenesis
      through direct and indirect mechanisms by targeting interleukin-8 and CXCL1
      secreted by the tumour endothelial and cancer cells. Using several experimental
      models, we demonstrate the therapeutic potential of miR-200 delivery in ovarian,
      lung, renal and basal-like breast cancers by inhibiting angiogenesis. Delivery of
      miR-200 members into the tumour endothelium resulted in marked reductions in
      metastasis and angiogenesis, and induced vascular normalization. The role of miR
      200 in blocking cancer angiogenesis in a cancer-dependent context defines its
      utility as a potential therapeutic agent. 

PMID- 24018978
TI  - First trimester screening for holoprosencephaly with choroid plexus morphology
      ('butterfly' sign) and biparietal diameter.
AB  - OBJECTIVE: The aim of this study was to determine whether choroid plexus
      morphology ('butterfly' sign) and biparietal diameter (BPD) are effective
      sonographic screening tools for holoprosencephaly (HPE) in the first trimester.
      METHODS: An axial view of the fetal head was obtained routinely to determine the
      presence of the 'butterfly' sign in pregnancies presenting for sonographic
      screening at 11-13 weeks of gestation. The same view was also used to obtain BPD
      measurements. The definitive diagnosis of HPE was established by the sonographic
      demonstration of an anterior cerebral monoventricular cavity and thalamic fusion.
      RESULTS: During a 9-year study period, 11 068 live fetuses were screened. There
      were 11 cases of HPE (prevalence 1/1006); all of them were detected by
      demonstration of an absent 'butterfly' sign with no false-positive cases. The BPD
      was less than the 5th percentile in 40% of the cases. CONCLUSIONS: The
      'butterfly' sign appears to be a highly sensitive marker for HPE in the first
      trimester. On the other hand, BPD measurements had a lower sensitivity, implying
      that microcephaly is not a prominent first-trimester feature in these cases.
      Incorporation of the 'butterfly' sign into the first trimester anatomy scan is
      simple and can facilitate the identification of the vast majority of fetuses with
      HPE in the first trimester.

PMID- 24018979
TI  - C-Src/Jak2/PDGFR/PKCdelta-dependent MMP-9 induction is required for thrombin
      stimulated rat brain astrocytes migration.
AB  - Among matrix metalloproteinases (MMPs), MMP-9 has been observed in patients with
      brain inflammatory diseases and may contribute to the pathology of brain
      diseases. Thrombin has been known as a regulator of MMP-9 expression and cells
      migration. However, the mechanisms underlying thrombin-induced MMP-9 expression
      in rat brain astrocytes (RBA-1 cells) were not completely understood. Here, we
      demonstrated that thrombin induced the expression of pro-form MMP-9 in RBA-1
      cells and cells migration which were attenuated by pretreatment with the
      inhibitor of receptor tyrosine kinase (Genistein), c-Src (PP1), Jak2 (AG490),
      PDGFR (AG1296), PI3K (LY294002), Akt (SH-5), PKCs (Ro318220), PKCdelta
      (Rottlerin), or NF-kappaB (Bay11-7082) and transfection with siRNA of c-Src,
      PDGFR, Akt, PKCdelta, ATF2, p65, IKKalpha, or IKKbeta. In addition, thrombin
      stimulated c-Src, Jak2, or PDGFR phosphorylation was inhibited by a thrombin
      inhibitor (PPACK), PP1, AG490, or AG1296. Thrombin further stimulated c-Src and
      PDGFR complex formation in RBA-1 cells. Thrombin also stimulated Akt and PKCdelta
      phosphorylation and PKCdelta translocation which were reduced by PPACK, PP1,
      AG490, AG1296, or LY294002. We further observed that thrombin markedly stimulated
      ATF2 or IkappaBalpha phosphorylation and NF-kappaB p65 translocation which were
      inhibited by Rottlerin or LY294002. Finally, thrombin stimulated in vivo binding
      of p65 to the MMP-9 promoter, which was reduced by pretreatment with Rottlerin or
      LY294002. These results concluded that in RBA-1 cells, thrombin activated a c
      Src/Jak2/PDGFR/PI3K/Akt/PKCdelta pathway, which in turn triggered ATF2 and NF
      kappaB activation and ultimately induced MMP-9 expression associated with cell
      migration.

PMID- 24018980
TI  - The complications and the position of the Codman MicroSensorTM ICP device: an
      analysis of 549 patients and 650 Sensors.
AB  - BACKGROUND: Complications of and insertion depth of the Codman MicroSensor ICP
      monitoring device (CMS) is not well studied. OBJECTIVE: To study complications
      and the insertion depth of the CMS in a clinical setting. METHODS: We identified
      all patients who had their intracranial pressure (ICP) monitored using a CMS
      device between 2002 and 2010. The medical records and post implantation computed
      tomography (CT) scans were analyzed for occurrence of infection, hemorrhage and
      insertion depth. RESULTS: In all, 549 patients were monitored using 650 CMS. Mean
      monitoring time was 7.0 +/- 4.9 days. The mean implantation depth was 21.3 +/-
      11.1 mm (0-88 mm). In 27 of the patients, a haematoma was identified; 26 of these
      were less than 1 ml, and one was 8 ml. No clinically significant bleeding was
      found. There was no statistically significant increase in the number of
      hemorrhages in presumed coagulopathic patients. The infection rate was 0.6 % and
      the calculated infection rate per 1,000 catheter days was 0.8. CONCLUSION: The
      risk for hemorrhagic and infectious complications when using the CMS for ICP
      monitoring is low. The depth of insertion varies considerably and should be taken
      into account if patients are treated with head elevation, since the pressure is
      measured at the tip of the sensor. To meet the need for ICP monitoring, an
      intraparenchymal ICP monitoring device should be preferred to the use of an
      external ventricular drainage (EVD).

PMID- 24018981
TI  - Percutaneous short-segment pedicle screw placement without fusion in the
      treatment of thoracolumbar burst fractures: is it effective?: comparative study
      with open short-segment pedicle screw fixation with posterolateral fusion.
AB  - BACKGROUND: Since introduction of the pedicle screw-rod system, short-segment
      pedicle screw fixation has been widely adopted for thoracolumbar burst fractures
      (TLBF). Recently, the percutaneous pedicle screw fixation (PPSF) systems have
      been introduced in spinal surgery; and it has become a popularly used method for
      the treatment of degenerative spinal disease. However, there are few clinical
      reports concerning the efficacy of PPSF without fusion in treatment of TLBF. The
      purpose of this study was to determine the efficacy and safety of short-segment
      PPSF without fusion in comparison to open short-segment pedicle screw fixation
      with bony fusion in treatment of TLBF. METHODS: This study included 59 patients,
      who underwent either percutaneous (n = 32) or open (n = 27) short-segment pedicle
      screw fixation for stabilization of TLBF between December 2003 and October 2009.
      Radiographs were obtained before surgery, immediately after surgery, and at the
      final follow-up for assessment of the restoration of the spinal column. For
      radiologic parameters, Cobb angle, vertebral wedge angle, and vertebral body
      compression ratio were assessed on a lateral thoracolumbar radiograph. For
      patient's pain and functional assessment, the visual analogue scale (VAS), the
      Frankel grading system, and Low Back Outcome Score (LBOS) were measured.
      Operation time, and the amount of intraoperative bleeding loss were also
      evaluated. FINDINGS: In both groups, regional kyphosis (Cobb angle) showed
      significant improvement immediately after surgery, which was maintained until the
      last follow up, compared with preoperative regional kyphosis. Postoperative
      correction loss showed no significant difference between the two groups at the
      final follow-up. In the percutaneous surgery group, there were significant
      declines of intraoperative blood loss, and operation time compared with the open
      surgery group. Clinical results showed that the percutaneous surgery group had a
      lower VAS score and a better LBOS at three months and six months after surgery;
      however, the outcomes were similar in the last follow-up. CONCLUSIONS: Both open
      and percutaneous short-segment pedicle fixation were safe and effective for
      treatment of TLBF. Although both groups showed favorable clinical and radiologic
      outcomes at the final follow-up, PPSF without bone graft provided earlier pain
      relief and functional improvement, compared with open TPSF with posterolateral
      bony fusion. Despite several shortcomings in this study, the result suggests that
      ongoing use of PPSF is recommended for the treatment of TLBF.

PMID- 24018982
TI  - Role of intraoperative neurophysiological monitoring during fluorescence-guided
      resection surgery : Aiming at seemingly complete resection of diffuse gliomas
      under 5-ALA guidance-Is it safe?

PMID- 24018983
TI  - Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy with
      oxaliplatin for peritoneal carcinomatosis arising from colorectal cancer.
AB  - BACKGROUND: Peritoneal carcinomatosis (PC) from colorectal cancer is associated
      with a poor prognosis. Cytoreductive surgery (CRS) with hyperthermic
      intraperitoneal chemotherapy (HIPEC) have improved survival compared to systemic
      chemotherapy. We evaluate the results of this treatment in our institution.
      METHODS: Treatment consisted of complete CRS followed by HIPEC with oxaliplatin
      (460 mg/m(2) ) in 2 L/m(2) of D5W at 42 degrees C during 30 min. RESULTS: From
      2004 to 2011, 40 patients with PC from colorectal cancer were included and 25 CRS
      + HIPEC were performed. Six patients had a negative second-look surgery and nine
      had unresectable disease. Median follow-up was 22.8 months. Overall 3- and 5-year
      survival rates for the cohort were 56% and 33%. The 3- and 5-year overall
      survival rates were 61% and 36% for HIPEC group, 82% and 67% for patients with
      negative second-look, and 22% and 0% for the unresectable group (P = 0.0087). 3
      year disease-free survival for HIPEC group was 22%. Major complication and
      mortality rate for HIPEC group were 20% and 4%. Peritoneal carcinomatosis index
      (P = 0.0374) and lymph node status (P = 0.027) were prognostic indicators.
      CONCLUSIONS: CRS + HIPEC with oxaliplatin for PC from colorectal cancer is an
      effective treatment with encouraging survival results.

PMID- 24018984
TI  - A naturally occurring defective DNA satellite associated with a monopartite
      begomovirus: evidence for recombination between alphasatellite and betasatellite.
AB  - Monopartite begomoviruses and their associated satellites form unique disease
      complexes that have emerged as a serious threat to agriculture worldwide. It is
      well known that frequent recombination contributes to the diversification and
      evolution of geminiviruses. In this study, we identified a novel defective
      satellite molecule (RecSat) in association with Tobacco leaf curl Yunnan virus
      (TbLCYNV) in a naturally infected tobacco plant. Sequence analysis showed that
      Recsat comprises 754 nucleotides in size and is a chimera involving
      alphasatellite and betasatellite sequences, containing both betasatellite
      conserved region and alphasatellite stem-loop structure. Recombination analysis
      revealed that RecSat has arisen from three independent recombination events
      likely involving Tomato yellow leaf curl China betasatellite, Ageratum yellow
      vein China betasatellite and Tobacco curly shoot alphasatellite. Co-inoculation
      of RecSat with TbLCYNV induced symptoms indistinguishable from those induced by
      TbLCYNV alone in Nicotiana benthamiana. Southern blot hybridization showed that
      RecSat could be trans-replicated stably in N. benthamiana plants by TbLCYNV, and
      impaired the accumulation of helper virus and co-inoculated alphasatellite. Our
      results provide the first evidence for recombination between two distinct types
      of satellites among geminivirus complex and highlight recombination as a driving
      force for geminivirus evolution. 

PMID- 24018985
TI  - Cognitive enrichment for bottlenose dolphins (Tursiops truncatus): evaluation of
      a novel underwater maze device.
AB  - Cognitive enrichment is gaining popularity as a tool to enhance captive animal
      well-being, but research on captive cetaceans is lacking. Dolphin cognition has
      been studied intensively since the 1950s, and several hundred bottlenose dolphins
      are housed in major zoos and aquaria worldwide, but most dolphin enrichment
      consists of simple floating objects. The aim of this study was to investigate
      whether a novel, underwater maze device (UMD) was cognitively enriching for one
      group of male and one group of female dolphins at Six Flags Discovery Kingdom,
      CA. The dolphin's task was to navigate a rubber ball through a maze of pipes,
      towards an exit pipe. We also tested a modification where an edible gelatine ball
      fell into the pool once the UMD was solved. The UMD was provided to each group
      between 8 and 11 times over a 4-week period. Male dolphins used the UMD without
      prior training, whereas females did not use the UMD at all. Two male dolphins
      solved the UMD 17 times, using a variety of problem-solving strategies. The UMD
      had no significant effect on circular (repetitive) swimming patterns, but males
      spent significantly more time underwater when the UMD was present. Males used the
      UMD significantly more when it contained the rubber ball, but the gelatine ball
      stimulated social play. The UMD is a safe and practical device for captive
      dolphins. It now requires further testing on other dolphins, particularly
      females, to in order to examine whether the sex differences we observed are a
      general phenomenon.

PMID- 24018986
TI  - Association between early-onset Parkinson disease and 22q11.2 deletion syndrome:
      identification of a novel genetic form of Parkinson disease and its clinical
      implications.
AB  - IMPORTANCE: Clinical case reports of parkinsonism co-occurring with hemizygous
      22q11.2 deletions and the associated multisystem syndrome, 22q11.2 deletion
      syndrome (22q11.2DS), suggest that 22q11.2 deletions may lead to increased risk
      of early-onset Parkinson disease (PD). The frequency of PD and its
      neuropathological presentation remain unknown in this common genetic condition.
      OBJECTIVE: To evaluate a possible association between 22q11.2 deletions and PD.
      DESIGN, SETTING, AND PARTICIPANTS: An observational study of the occurrence of PD
      in the world's largest cohort of well-characterized adults with a molecularly
      confirmed diagnosis of 22q11.2DS (n = 159 [6 with postmortem tissue]; age range,
      18.1-68.6 years) was conducted in Toronto, Ontario, Canada. Rare postmortem brain
      tissue from individuals with 22q11.2DS and a clinical history of PD was
      investigated for neurodegenerative changes and compared with that from
      individuals with no history of a movement disorder. MAIN OUTCOMES AND MEASURES: A
      clinical diagnosis of PD made by a neurologist and neuropathological features of
      PD. RESULTS Adults with 22q11.2DS had a significantly elevated occurrence of PD
      compared with standard population estimates (standardized morbidity ratio = 69.7;
      95% CI, 19.0-178.5). All cases showed early onset and typical PD symptom pattern,
      treatment response, and course. All were negative for family history of PD and
      known pathogenic PD-related mutations. The common use of antipsychotics in
      patients with 22q11.2DS to manage associated psychiatric symptoms delayed
      diagnosis of PD by up to 10 years. Postmortem brain tissue revealed classic loss
      of midbrain dopaminergic neurons in all 3 postmortem 22q11.2DS-PD cases. Typical
      alpha-synuclein-positive Lewy bodies were present in the expected distribution in
      2 cases but absent in another. CONCLUSIONS AND RELEVANCE: These findings suggest
      that 22q11.2 deletions represent a novel genetic risk factor for early-onset PD
      with variable neuropathological presentation reminiscent of LRRK2-associated PD
      neuropathology. Individuals with early-onset PD and classic features of 22q11.2DS
      should be considered for genetic testing, and those with a known 22q11.2 deletion
      should be monitored for the development of parkinsonian symptoms. Molecular
      studies of the implicated genes, including DGCR8, may help shed light on the
      underlying pathophysiology of PD in 22q11.2DS and idiopathic PD.

PMID- 24018987
TI  - A failure analysis of invasive breast cancer: most deaths from disease occur in
      women not regularly screened.
AB  - BACKGROUND: Mortality reduction from mammographic screening is controversial.
      Individual randomized trials and meta-analyses demonstrate statistically
      significant mortality reductions in all age groups invited to screening. In women
      actually screened, mortality reductions are greater. Individual trials and meta
      analyses show varying rates of mortality reduction, leading to questions about
      screening's value and whether treatment advances have diminished the importance
      of early detection. This study hypothesized that breast cancer deaths
      predominantly occurred in unscreened women. METHODS: Invasive breast cancers
      diagnosed between 1990 and 1999 were followed through 2007. Data included
      demographics, mammography use, surgical and pathology reports, and recurrence and
      death dates. Mammograms were categorized as screening or diagnostic based on
      absence or presence of breast signs or symptoms, and were substantiated by
      medical records. Breast cancer deaths were defined after documentation of prior
      distant metastases. Absence of recurrent cancer and lethal other diseases defined
      death from other causes. RESULTS: Invasive breast cancer failure analysis defined
      7301 patients between 1990 and 1999, with 1705 documented deaths from breast
      cancer (n = 609) or other causes (n = 905). Among 609 confirmed breast cancer
      deaths, 29% were among women who had been screened (19% screen-detected and 10%
      interval cancers), whereas 71% were among unscreened women, including > 2 years
      since last mammogram (6%), or never screened (65%). Overall, 29% of cancer deaths
      were screened, whereas 71% were unscreened. Median age at diagnosis of fatal
      cancers was 49 years; in deaths not from breast cancer, median age at diagnosis
      was 72 years. CONCLUSIONS: Most deaths from breast cancer occur in unscreened
      women. To maximize mortality reduction and life-years gained, initiation of
      regular screening before age 50 years should be encouraged.

PMID- 24018989
TI  - Water desorption from nanostructured graphite surfaces.
AB  - Water interaction with nanostructured graphite surfaces is strongly dependent on
      the surface morphology. In this work, temperature programmed desorption (TPD) in
      combination with quadrupole mass spectrometry (QMS) has been used to study water
      ice desorption from a nanostructured graphite surface. This model surface was
      fabricated by hole-mask colloidal lithography (HCL) along with oxygen plasma
      etching and consists of a rough carbon surface covered by well defined structures
      of highly oriented pyrolytic graphite (HOPG). The results are compared with those
      from pristine HOPG and a rough (oxygen plasma etched) carbon surface without
      graphite nanostructures. The samples were characterized using scanning electron
      microscopy (SEM) and atomic force microscopy (AFM). The TPD experiments were
      conducted for H2O coverages obtained after exposures between 0.2 and 55 langmuir
      (L) and reveal a complex desorption behaviour. The spectra from the
      nanostructured surface show additional, coverage dependent desorption peaks. They
      are assigned to water bound in two-dimensional (2D) and three-dimensional (3D)
      hydrogen-bonded networks, defect-bound water, and to water intercalated into the
      graphite structures. The intercalation is more pronounced for the nanostructured
      graphite surface in comparison to HOPG surfaces because of a higher concentration
      of intersheet openings. From the TPD spectra, the desorption energies for water
      bound in 2D and 3D (multilayer) networks were determined to be 0.32 +/- 0.06 and
      0.41 +/- 0.03 eV per molecule, respectively. An upper limit for the desorption
      energy for defect-bound water was estimated to be 1 eV per molecule. 

PMID- 24018988
TI  - Mutations in KCNJ11 are associated with the development of autosomal dominant,
      early-onset type 2 diabetes.
AB  - AIMS/HYPOTHESIS: More than 90% of Chinese familial early-onset type 2 diabetes
      mellitus is genetically unexplained. To investigate the molecular aetiology, we
      identified and characterised whether mutations in the KCNJ11 gene are responsible
      for these families. METHODS: KCNJ11 mutations were screened for 96 familial early
      onset type 2 diabetic probands and their families. Functional significance of the
      identified mutations was confirmed by physiological analysis, molecular modelling
      and population survey. RESULTS: Three novel KCNJ11 mutations, R27H, R192H and
      S116F117del, were identified in three families with early-onset type 2 diabetes
      mellitus. Mutated KCNJ11 with R27H or R192H markedly reduced ATP sensitivity
      (E23K>R27H>C42R>R192H>R201H), but no ATP-sensitive potassium channel currents
      were detected in the loss-of-function S116F117del channel in vitro. Molecular
      modelling indicated that R192H had a larger effect on the channel ATP-binding
      pocket than R27H, which may qualitatively explain why the ATP sensitivity of the
      R192H mutation is seven times less than R27H. The shape of the S116F117del
      channel may be compressed, which may explain why the mutated channel had no
      currents. Discontinuation of insulin and implementation of sulfonylureas for R27H
      or R192H carriers and continuation/switch to insulin therapy for S116F117del
      carriers resulted in good glycaemic control. CONCLUSIONS/INTERPRETATION: Our
      results suggest that genetic diagnosis for the KCNJ11 mutations in familial early
      onset type 2 diabetes mellitus may help in understanding the molecular aetiology
      and in providing more personalised treatment for these specific forms of diabetes
      in Chinese and other Asian patients.

PMID- 24018990
TI  - Pro-Gly mediated conformational switch of mycobacteriophage D29 holin
      transmembrane domain I is lipid concentration driven.
AB  - Biophysical and spectroscopic analysis of synthetic transmembrane domain I (1) of
      mycobacteriophage D29 holin shows a lipid concentration dependent conformational
      switch from an alpha-helix to a beta-sheet structure. The reversibility of this
      switch, upon change in the lipid-to-peptide ratio, requires a central Pro-Gly
      segment, and is abolished upon mutation to Ala-Ala or (D)Pro-Gly.

PMID- 24018991
TI  - Origin of chains of Au-PbS nano-dumbbells in space.
AB  - Self-assembled, one-dimensional (1D) nanomaterials are amenable building blocks
      for bottom-up nanofabrication processes. A current shortcoming in the self
      assembly of 1D nanomaterials in solution phase is the need for specific linkers
      or templates under very precise conditions to achieve a handful of systems. Here
      we report on the origin of a novel self-assembly of 1D dumbbells consisting of Au
      tipped PbS nanorods into stable chains in solution without any linkers or
      templates. A realistic multi-particle model suggests that the mesophase comprises
      1D dumbbells arrayed in chains formed by anisotropic van der Waals type
      interactions. We demonstrate an alternative recognition mechanism for directing
      the assembly of the 1D dumbbells, based on effective interaction between the
      neighboring dumbbells consisting of Au tips with complementary crystallographic
      facets that guides the entire assembly in space. 

PMID- 24018992
TI  - Ethics and organizational research.

PMID- 24018993
TI  - International Journal of Occupational Medicine and Environmental Health.
      Editorial.

PMID- 24018994
TI  - Health and life style-related determinants of survival rate in the male residents
      of the city of Lodz.
AB  - INTRODUCTION: The article presents a selected part of an analysis of health- and
      lifestyle-related determinants of the longevity of male residents of the city of
      Lodz. The WHO strategy for the European region assumes that the term' lifestyle'
      refers to the way of life based on the association between conditions of life
      understood in a broad sense and individual patterns of behaviour determined by
      socio-cultural factors and individual features. On this basis, the aim of this
      study is to identify the multiple statistical relationships on the mortality of
      men living in Lodz, particularly the influence of the following variables on the
      probability of survival: age, subjective health assessment, nutritional habits,
      alcohol consumption and tobacco smoking. MATERIALS AND METHODS: The study sample
      (1004 respondents) was selected, and the study was carried out, based on the
      standards of the CINDI WHO Programme. The investigations included socio
      demographic data, health status, lifestyle and anthropometric measurements.
      RESULTS: From the results of the first-study performed in Poland of the longevity
      of men with identified risk factors of cardiovascular diseases, it has been found
      that: 1) Tobacco smoking has a negative influence on male longevity; 2) Alcohol
      consumed in moderate amounts favours male longevity; 3) The level of physical
      activity observed among the studied men was too low to affect longevity; 4) A
      diet rich in fish and consumption of yellow cheese are positive predictors of
      longevity, while additional use of table salt at meals and consumption of sweets
      (cakes) are negative ones. CONCLUSIONS: Risky lifestyles and a reluctance to
      abandon them are responsible for a shorter lifespan among men in Poland. Reducing
      this difference between women and men is a real challenge for public health
      professionals and preventive medicine specialists.

PMID- 24018995
TI  - The role of general and occupational stress in the relationship between
      workaholism and work-family/family-work conflicts.
AB  - INTRODUCTION: The purpose of this study was to analyze the role of general and
      occupational stress in the relationship between workaholism (recognized in two
      ways: as addiction and as behavioral tendency) and the intensity of work-family
      and family-work conflict. MATERIALS AND METHODS: The study included 178 working
      people. The survey was conducted at three stages - half a year before a holiday,
      right after the holiday and half a year after the holiday. The Excessive Work
      Involvement Scale (SZAP) by Golinska for the measurement of workaholism
      recognized as addiction; The Scale of Workaholism as Behavioral Tendencies (SWBT)
      by Mudrack and Naughton as adapted by Dudek et al for the measurement of
      workaholism as behavioral tendency; the Perceived Stress Scale by Cohen et al.,
      as adapted by Juczynski for the measurement of general stress; the Scale of
      Occupational Stress by Stanton in the adaptation of Dudek and Hauk for
      measurement of occupational stress; the Scale of Work-Family Conflict WFC/FWC by
      Netemeyer et al. with the Polish adaptation of A.M. Zalewska. Workaholism was
      measured once - before a holiday, the explained and intervening variables (the
      level of conflicts and stress, respectively) were measured at three stages. To
      test the mediating role of general and occupational stress, hierarchical
      regression analysis as well as the method of bootstrapping were applied. RESULTS
      AND CONCLUSIONS: Our results indicate that general stress is an important
      mediator of the relationship between workaholism recognized as an addiction and
      work-family conflicts. Occupational stress turned out to be the only mediator in
      the relationship between workaholism (recognized as an addiction) and the work
      family conflict, noted exclusively in the first stage of the study. Both general
      and occupational stress were not significant mediators in the relationship
      between workaholism recognized as a behavioral tendency and the conflicts
      described.

PMID- 24018996
TI  - The medical perspective on burnout.
AB  - OBJECTIVE: The aim of this study was to review recent medical findings related to
      burnout, its diagnosis, treatment, characteristic pathophysiological features,
      and preventive measures. MATERIALS AND METHODS: A systematic review of the
      scientific literature in PubMed/Medline was performed. The most recent and
      important findings were reported. RESULTS: Burnout was found to be a risk factor
      for myocardial infarction and coronary heart disease. It was also related to
      reduced fibrinolytic capacity, decreased capacity to cope with stress and
      hypothalamic-pituitary-adrenal (HPA) axis hypoactivity. Severe burnout symptoms
      are associated with a lower level or smaller increase of the cortisol awakening
      response (CAR), higher dehydroepiandrosterone-sulphate (DHEAS) levels, lower
      cortisol/DHEAS ratios and stronger suppression as measured by the dexamethasone
      suppression test (DST). More and more literature works suggest that the
      evaluation of the HPA axis should be brought to the attention of primary care
      physicians. There is no universal agreement on specific treatment and diagnostic
      measures to evaluate the wide range of HPA axis disorders. The cost-effective
      evaluation of adrenal hormones via saliva samples by a primary care physician may
      significantly alter the course of therapy in numerous chronic disease patients.
      Psychiatric disorders may have similar symptoms, but they have distinctive
      hormonal profiles. Having burnout recognized as a medical condition would help in
      differentiating burnout from similar clinical syndromes, such as depression or
      anxiety, and provide appropriate treatment to burnout patients. Proper treatment
      is essential for a fast and full recovery. CONCLUSION: Chronic stress-related
      disorders often fall outside the category of a "true" disease and are often
      treated as depression or not treated at all. The evaluation of adrenal hormones
      via saliva samples helps to predict burnout. Burnout screening techniques,
      dietary and nutritional guidelines and lifestyle changes for supporting the HPA
      function need to be developed. The presented material includes hormonal, dietary,
      and pharmaceutical perspectives.

PMID- 24018997
TI  - Occupational diseases in Poland--an overview of current trends.
AB  - INTRODUCTION: The number of occupational diseases (OD) recorded in Poland in the
      1990's rapidly increased, and the number of recognized cases has steadily
      decreased until now. Hence, it was decided to demonstrate the trends of selected
      pathologies which in Poland are "underestimated" in comparison to other
      countries. The presented data may constitute a basis for further research into
      the dependence of OD on socio-economic factors. MATERIALS AND METHODS:
      Occupational Disease Reporting Forms, completed and sent obligatorily by the
      state health inspectors to the Central Register of Occupational Diseases were
      used as source documents for analysis. This work analyzes changes in the
      incidence of chronic poisonings, asbestosis, voice organ diseases, cancers, viral
      hepatitis, asthma and the musculoskeletal disorders over the years 1998-2011.
      RESULTS: In 1998, the total number of registered diseases reached the maximum -
      12,017 cases, which fell in the subsequent years to 2,562 cases in 2011. During
      that period, the incidence rate decreased by 6 cases per year per 100,000
      employees. A considerable decrease, exceeding 90% of cases, was observed in voice
      organ disorders, hearing loss, chronic poisonings and viral hepatitis. The
      abovementioned changes, as well as improved detection of asbestos-related
      diseases through implementing a medical examination program of former asbestos
      processing plant workers, are advantages of the current situation in the
      epidemiology of OD. However, the disadvantages include underestimation, in
      comparison to other countries, of asthma, cancer and pathologies of the
      musculoskeletal system. CONCLUSION: The reported data indicates the need to
      assess the occupational fraction of the underestimated pathologies present in the
      work environment in Poland, as well as the need for studies aimed at clarifying
      the effect of systemic factors on identifying their occupational background.

PMID- 24018998
TI  - Potentially pathogenic yeasts from soil of children's recreational areas in the
      city of Lodz (Poland).
AB  - OBJECTIVES: Yeasts may become potential human and animal pathogens, particularly
      for individuals with a depressed immune system. Their presence in the
      environment, especially in soil, may favour their spread into human ontocenoses.
      MATERIALS AND METHODS: Eighty-four soil samples obtained from 21 children's
      recreational sites in Lodz in autumn 2010 and spring 2011 were evaluated. The
      yeasts were isolated by classical microbiological methods and identified on the
      basis of morphological and biochemical features. RESULTS: The fungi were found in
      73.8% and in 69.0% of the examined samples collected in autumn and spring,
      respectively. Among 97 isolates of yeasts, the species potentially pathogenic to
      humans and animals were Candida colliculosa, C. guilliermondii, C. humicola, C.
      inconspicua, C. lambica, C. lusitaniae, C. pelliculosa, C. tropicalis,
      Cryptococcus albidus, C. laurentii, C. neoformans, C. terreus, Kloeckera
      japonica, Geotrichum candidum, G. penicillatum, Rhodotorula mucilaginosa, R.
      glutinis, Saccharomyces cerevisiae, Sporobolomyces salmonicolor and Trichosporon
      cutaneum. The most frequently isolated fungi included the genus Cryptococcus (38
      isolates) and two species: Rhodotorula glutinis (15), Trichosporon cutaneum (14).
      C. neoformans, an etiological factor of cryptococcal meningitis, was present in
      the sandpits of 3 kindergartens. The Candida species were identified from park
      playgrounds and school sports fields mainly in autumn 2010 (14 isolates), in
      spring 2011 - only 1 isolate. The concentration of fungal species in particular
      samples varied considerably, but in the majority of samples, fungi were present
      at concentration of up to 1*10(2) CFU/1 g of soil. CONCLUSIONS: Yeasts were
      present in the soil of parks, schools and kindergarten recreational areas; the
      fact may pose a health risk to humans, especially to children, and this type of
      biological pollution should be regarded as a potential public health concern.

PMID- 24019000
TI  - TINCR, staufen1, and cellular differentiation.
AB  - The human genome encodes several thousand long non-protein coding transcripts>200
      nucleotides in length, a subset of which were shown to play important roles in
      regulation of gene expression. We recently identified TINCR, a lncRNA required
      for induction of key differentiation genes in epidermal tissue, including genes
      mutated in human skin diseases characterized by disrupted epidermal barrier
      formation. High-throughput analyses of TINCR RNA- and protein-interactomes
      revealed TINCR interaction with differentiation mRNAs as well as the Staufen1
      protein. TINCR, together with Staufen1, seems to stabilize a subset of mRNAs
      required for epidermal differentiation. Here, we discuss the emerging roles of
      Staufen1 and TINCR in the regulation of mammalian cell differentiation mediated
      by interaction with target mRNAs. We consider a role for TINCR as an epithelial
      specific guide for targeting the Staufen1 protein to specific mRNAs, reflecting
      the increasing complexity of gene regulatory processes in mammalian cells and
      tissue. 

PMID- 24019002
TI  - The diversity of bioethics.

PMID- 24019001
TI  - Non-invasive in vivo assessment of IDH1 mutational status in glioma.
AB  - Gain-of-function mutations of the isocitrate dehydrogenase 1 (IDH1) gene are
      among the most prevalent in low-grade gliomas and secondary glioblastoma. They
      lead to intracellular accumulation of the oncometabolite 2-hydroxyglutarate,
      represent an early pathogenic event and are considered a therapeutic target. Here
      we show, in this proof-of-concept study, that [1-(13)C] alpha-ketoglutarate can
      serve as a metabolic imaging agent for non-invasive, real-time, in vivo
      monitoring of mutant IDH1 activity, and can inform on IDH1 status. Using (13)C
      magnetic resonance spectroscopy in combination with dissolution dynamic nuclear
      polarization, the metabolic fate of hyperpolarized [1-(13)C] alpha-ketoglutarate
      is studied in isogenic glioblastoma cells that differ only in their IDH1 status.
      In lysates and tumours that express wild-type IDH1, only hyperpolarized [1-(13)C]
      alpha-ketoglutarate can be detected. In contrast, in cells that express mutant
      IDH1, hyperpolarized [1-(13)C] 2-hydroxyglutarate is also observed, both in cell
      lysates and in vivo in orthotopic tumours. 

PMID- 24019003
TI  - Dnmt2 methyltransferases and immunity: an ancient overlooked connection between
      nucleotide modification and host defense?
AB  - Many species maintain cytosine DNA methyltransferase (MTase) genes belonging to
      the Dnmt2 family. Prokaryotic modification-restriction systems utilize DNA
      methylation to distinguish between self and foreign DNA, and cytosine methylation
      in eukaryotic DNA contributes to epigenetic mechanisms that control gene
      expression. However, Dnmt2 proteins display only low or no DNA MTase activity,
      making this protein family the odd and enigmatic family member. Recent evidence
      showed that Dnmt2 proteins are not DNA but RNA MTases with functions in
      biological processes as diverse as stress responses and RNA-mediated inheritance.
      These observations not only raise profound questions regarding the perceived
      substrate specificities of cytosine MTase, but also suggest links between DNA and
      RNA modification systems. Here, we speculate that Dnmt2 proteins might be part of
      an ancient cytosine modification toolbox that is used to successfully respond to
      environmental challenges, including constantly evolving RNA and DNA substrates. 

PMID- 24019004
TI  - Swiss prospective study on spider bites.
AB  - Knowledge of spider bites in Central Europe derives mainly from anecdotal case
      presentations; therefore we aimed to collect cases systematically. From June 2011
      to November 2012 we prospectively collected 17 cases of alleged spider bites, and
      together with two spontaneous notifications later on, our database totaled 19
      cases. Among them, eight cases could be verified. The causative species were:
      Cheiracanthium punctorium (3), Zoropsis spinimana (2), Amaurobius ferox,
      Tegenaria atrica and Malthonica ferruginea (1 each). Clinical presentation was
      generally mild, with the exception of Cheiracanthium punctorium, and patients
      recovered fully without sequelae. In Switzerland, spider bites generally have a
      benign clinical course, which is characterised by minor effects, with rapid and
      complete recovery. Since only verified spider bites can be regarded as spider
      bites, in the case of clinically important arachnidism, the spider should be sent
      to an expert for identification. Our study may help to diminish spider fear and
      reassure people who have experienced a bite. 

PMID- 24019005
TI  - Breaking the concentration limit of optical single-molecule detection.
AB  - Over the last decade, single-molecule detection has been successfully utilized in
      the life sciences and materials science. Yet, single-molecule measurements only
      yield meaningful results when working in a suitable, narrow concentration range.
      On the one hand, diffraction limits the minimal size of the observation volume in
      optical single-molecule measurements and consequently a sample must be adequately
      diluted so that only one molecule resides within the observation volume. On the
      other hand, at ultra-low concentrations relevant for sensing, the detection
      volume has to be increased in order to detect molecules in a reasonable timespan.
      This in turn results in the loss of an optimal signal-to-noise ratio necessary
      for single-molecule detection. This review discusses the requirements for
      effective single-molecule fluorescence applications, reflects on the motivation
      for the extension of the dynamic concentration range of single-molecule
      measurements and reviews various approaches that have been introduced recently to
      solve these issues. For the high-concentration limit, we identify four promising
      strategies including molecular confinement, optical observation volume reduction,
      temporal separation of signals and well-conceived experimental designs that
      specifically circumvent the high concentration limit. The low concentration limit
      is addressed by increasing the measurement speed, parallelization, signal
      amplification and preconcentration. The further development of these ideas will
      expand our possibilities to interrogate research questions with the clarity and
      precision provided only by the single-molecule approach. 

PMID- 24019006
TI  - Validation of activPAL defined sedentary time and breaks in sedentary time in 4-
      to 6-year-olds.
AB  - This study examined the classification accuracy of the activPAL, including total
      time spent sedentary and total number of breaks in sedentary behavior (SB) in 4-
      to 6-year-old children. Forty children aged 4-6 years (5.3 +/- 1.0 years)
      completed a ~150-min laboratory protocol involving sedentary, light, and moderate
      to vigorous-intensity activities. Posture was coded as sit/lie, stand, walk, or
      other using direct observation. Posture was classified using the activPAL
      software. Classification accuracy was evaluated using sensitivity, specificity
      and area under the receiver operating characteristic curve (ROC-AUC). Time spent
      in each posture and total number of breaks in SB were compared using paired
      sample t-tests. The activPAL showed good classification accuracy for sitting (ROC
      AUC = 0.84) and fair classification accuracy for standing and walking (0.76 and
      0.73, respectively). Time spent in sit/lie and stand was overestimated by 5.9%
      (95% CI = 0.6-11.1%) and 14.8% (11.6-17.9%), respectively; walking was
      underestimated by 10.0% (-12.9-7.0%). Total number of breaks in SB were
      significantly overestimated (55 +/- 27 over the course of the protocol; p < .01).
      The activPAL performed well when classifying postures in young children. However,
      the activPAL has difficulty classifying other postures, such as kneeling. In
      addition, when predicting time spent in different postures and total number of
      breaks in SB the activPAL appeared not to be accurate. 

PMID- 24019007
TI  - Chemical functionalization of exfoliated graphene.
AB  - Graphene is turning out to be the material that will effectively kick-start a new
      era for nanotechnology. The impressive properties of this atom-thick carbon layer
      are taking shape and form with early reports of successful applications based on
      it. The turning point for this material will be its low-cost mass production. In
      this report a chemist's perspective on the production methods for graphene and
      the subsequent functionalization processes is discussed. 

PMID- 24019008
TI  - Effects of changeover delay on response allocation during probe tests.
AB  - The present study assessed whether a pattern of responding that develops when
      choosing between two alternatives generalizes to novel choice tests when
      alternatives are presented in new combinations. Pigeons were trained on a two
      component multiple schedule. In both components, a concurrent variable-interval
      (VI) 40-s VI 80-s schedule was used. The COD was 1 s in one component and 10 s in
      the other. The long COD produced consistently longer dwell times than the short
      COD did. Following training, subjects were presented with four types of probe
      test components in which one alternative was drawn from the component with the
      short COD and one alternative was drawn from the component with the long COD.
      When the schedule values of the two alternatives were identical (VI 40 vs. VI 40
      and VI 80 vs. VI 80), subjects preferred the alternative trained with the long
      COD (Ms = .78 and .61, respectively). Additionally, subjects preferred the VI 40
      s alternative trained with the long COD to the VI 80-s alternative that was
      trained with the short COD (M = .85). Systematic preference was not observed when
      subjects were given a choice between the VI 40-s alternative that was trained
      with the short COD and the VI 80-s alternative that was trained with the long
      COD. These results demonstrate that a stimulus associated with a longer COD, and
      thus longer dwell times in baseline training, may be more preferred during probe
      tests than expected on the basis of the rate of primary reinforcement associated
      with that stimulus. 

PMID- 24019009
TI  - Varying the costs of sunk costs: optimal and non-optimal choices in a sunk-cost
      task with humans.
AB  - Twelve adult human subjects were exposed to a sunk-cost procedure with two
      options: a mixed-ratio schedule of points later exchangeable for money, and an
      escape schedule that cancelled the current trial and initiated a new one. The
      mixed ratio included four values, arranged probabilistically in such a way that
      the expected ratios favored either persistence or escape. These probabilities
      were varied systematically on a within-subject basis across conditions. Absolute
      ratio size was thus varied across four groups of three subjects each, yielding
      unique combinations of expected ratios from escaping and persisting. When the
      differences between escaping and persisting differed the least, subjects tended
      to persist, committing the sunk-cost error. When the differences between
      persisting and escaping differed by a larger margin, choice patterns tended
      toward optimal-escaping or persisting as a function of the contingencies. These
      findings demonstrate that sunk-cost decision-making errors in humans are
      sensitive to their relative costs and benefits, and illustrate a promising set of
      methods for bringing such behavior under experimental control in the laboratory. 

PMID- 24019011
TI  - Alfred Russel Wallace's world of final causes.
AB  - Alfred Russel Wallace (1823-1913) is an important figure in the history of
      science, but there remain many questions about the nature of his world view, and
      how it developed. Here, Wallace's appreciation of the role of final causes in
      evolution is linked to some of its probable origins, with an emphasis on the
      influence of Alexander von Humboldt (1769-1859). The question is then asked
      whether a final causes-based scientific agenda might be possible, and answered by
      drawing attention to two current efforts in that direction by Adrian Bejan, and
      by the author. A sketch of the latter approach, adapted from Spinozian thinking,
      is given, with an empirical example involving drainage basin morphology that
      suggests structural influences of a final causes sort. 

PMID- 24019010
TI  - Combination lamivudine and adefovir versus entecavir for the treatment of naive
      chronic hepatitis B patients: a pilot study.
AB  - BACKGROUND: The aim of this study was to compare the effect of combination
      lamivudine (LAM) and adefovir dipivoxil (ADV) versus entecavir (ETV) monotherapy
      for naive HBeAg-positive chronic hepatitis B (CHB) patients. MATERIAL/METHODS:
      Fifty enrolled patients with CHB were evenly divided into 2 groups: a group
      treated with of lamivudine (LAM) (100 mg/day) plus adefovir (ADV) (10 mg/day)
      combination, and a group treated with entecavir (ETV) (0.5 mg/day). Serum levels
      of ALT, AST, creatinine, bilirubin, HBsAg, HBeAg and HBV viral load, and
      genotypic resistance were analyzed at 0, 12, 24, 52, and 104 weeks. HBV DNA
      levels were determined by real-time PCR and HBsAg and HBeAg by chemiluminescence.
      Serum levels of ALT, AST, creatinine, and bilirubin were measured by an automatic
      biochemical analyzer. Data analysis was performed with SPSS 12.0 software.
      RESULTS: There were no significant differences in the virological response (VR)
      rates between LAM+ADV and ETV cohorts at 24, 52, and 104 weeks (P>0.05). The
      HBeAg seroconversion rates were 28% and 20%, and the biochemical response (BR)
      rates were 88% and 84% at week 104 in the LAM+ADV and ETV groups, respectively.
      The rates of undetectable HBV DNA, HBeAg seroconversion, and ALT normalization
      rates were similar in both cohorts. No virological breakthrough or serious
      adverse effects were noted for any patient during the study period. CONCLUSIONS:
      Both LAM+ADV combination therapy and ETV monotherapy were effective and safe in
      the treatment of -naive HBeAg-positive CHB patients. However, further studies are
      needed to obtain long-term results.

PMID- 24019012
TI  - Quantifying the impact of storage procedures for faecal bacteriotherapy in the
      critically endangered New Zealand parrot, the kakapo (Strigops habroptilus).
AB  - The endemic New Zealand kakapo is classified as 'critically endangered' and, in
      an effort to prevent extinction and restore the kakapo population, intensive
      handling of rare kakapo chicks is often utilised to reduce mortality and improve
      health outcomes among juveniles. Due to concerns that hand-reared chicks may not
      receive a full bacterial complement in their gut in the absence of regurgitated
      food from their mother, conservation workers feed a suspension of frozen adult
      faeces to captive chicks. However, the efficacy of this practice is unknown, with
      no information about the viability of these bacteria, or whether certain
      bacterial taxa are selected for or against as a consequence of freezing. In this
      study we experimentally determined the effects of freezing and reanimation on
      bacterial cell viability and diversity, using a faecal sample obtained from a
      healthy adult kakapo. Freezing reduced the number of viable bacterial cells
      (estimated by colony-forming units, CFU) by 99.86%, although addition of a
      cryoprotectant prior to freezing resulted in recovery of bacterial cells
      equivalent to that of non-frozen controls. Bacterial taxonomic diversity was
      reduced by freezing, irrespective of the presence of a cryoprotectant. While this
      study did not address the efficacy of faecal supplementation per se, the obtained
      data do suggest that faecal bacteriotherapy using frozen faeces (with a
      cryoprotectant) from healthy adult birds warrants further consideration as a
      conservation strategy for intensively managed species.

PMID- 24019014
TI  - Extracellular vesicle-mediated transfer of membranous components from the highly
      malignant T24 urinary carcinoma cell line to the non-malignant RT4 urinary
      papilloma cell line.
AB  - This communication reports the first experimental evidence that in the bladder
      cancer model, membranous components labelled with the DiO dye and the cholera
      toxin subunit B can be transported from highly malignant (T24) to non-malignant
      (RT4) cells by extracellular vesicles. Taking into account the presence of stable
      membranous nanostructures found by scanning electron microscopy, we suggest a
      possible uptake mechanism in recipient cells through fusion with highly curved
      membranous regions. 

PMID- 24019016
TI  - Obesity interventions can improve more than just body mass index.

PMID- 24019017
TI  - Integrated prototype nanodevices via SnO2 nanoparticles decorated SnSe
      nanosheets.
AB  - Hybrid materials made from all inorganic components are intriguing in many
      fields, because they have shown in-depth potential use for electronic and
      optoelectronic applications including solar cells, gas sensors, photodetectors,
      and field effect transistors. Hybrid materials made from SnO2 nanoparticles on
      SnSe nanosheets have been synthesized via a facile, lost-cost and safe solution
      method, and have been demonstrated as promising multifunctional materials in
      various prototype devices, including gas sensors, photodetectors, and field
      effect transistors.

PMID- 24019013
TI  - Receptor-mediated transport of vacuolar proteins: a critical analysis and a new
      model.
AB  - In this article we challenge the widely accepted view that receptors for soluble
      vacuolar proteins (VSRs) bind to their ligands at the trans-Golgi network (TGN)
      and transport this cargo via clathrin-coated vesicles (CCV) to a multivesicular
      prevacuolar compartment. This notion, which we term the "classical model" for
      vacuolar protein sorting, further assumes that low pH in the prevacuolar
      compartment causes VSR-ligand dissociation, resulting in a retromer-mediated
      retrieval of the VSRs to the TGN. We have carefully evaluated the literature with
      respect to morphology and function of the compartments involved, localization of
      key components of the sorting machinery, and conclude that there is little direct
      evidence in its favour. Firstly, unlike mammalian cells where the sorting
      receptor for lysosomal hydrolases recognizes its ligand in the TGN, the available
      data suggests that in plants VSRs interact with vacuolar cargo ligands already in
      the endoplasmic reticulum. Secondly, the evidence supporting the packaging of VSR
      ligand complexes into CCV at the TGN is not conclusive. Thirdly, the prevacuolar
      compartment appears to have a pH unsuitable for VSR-ligand dissociation and lacks
      the retromer core and the sorting nexins needed for VSR recycling. We present an
      alternative model for protein sorting in the TGN that draws attention to the much
      overlooked role of Ca(2+) in VSR-ligand interactions and which may possibly also
      be a factor in the sequestration of secretory proteins.

PMID- 24019018
TI  - No evidence for directional biases in inhibition of return.
AB  - The phenomenon of "inhibition of return" (IOR) has been the subject of
      considerable research interest for nearly 30 years. Two reports claiming
      directional biases in IOR (Spalek & Hammad, Perception & Psychophysics 66:219
      233, 2004, Psychological Science 16:15-18, 2005) were examined more closely, as
      such findings challenge the theoretical role attributed to IOR and imply that
      this purported mechanism for the facilitation of visual search would bias search
      in systematic ways. The data from two new experiments, as well as reanalysis of
      the original data, showed the reports to result from an unconventional method of
      calculating IOR that confounded visual field with target location. Although we
      found significant differences in target detection response times between the
      visual fields, directional biases were absent from all of the examined data when
      the conventional method of computing IOR was applied.

PMID- 24019019
TI  - Comparative study between mobile computed radiography and mobile flat-panel
      radiography for bedside chest radiography: impact of an antiscatter grid on the
      visibility of selected diagnostically relevant structures.
AB  - OBJECTIVES: The objective of this study was to evaluate the diagnostic
      performance of 2 different imaging systems in adult bedside chest radiography and
      the impact on the visibility of selected diagnostically relevant structures in
      the images acquired with these systems, with and without an antiscatter grid.
      MATERIALS AND METHODS: We acquired bedside chest radiographs of 103 intensive
      care patients (36 women, 67 men; age range, 17-90 years; mean age, 66.4 years)
      using 4 acquisition techniques (computed radiography [CR] and digital radiography
      [DR], with and without grid). Image quality was evaluated independently by 4
      radiologists using a 9-point visibility scale. Evaluated were lung parenchyma,
      soft tissues, thoracic spine, foreign bodies, and the overall image quality.
      Interobserver agreement and differences between the systems were tested using an
      interclass correlation (ICC) test. Mean scores were compared using the analysis
      of variance, followed by the post hoc pairwise testing (the Tukey test) in case
      of multiple group comparisons and by the Student t test in case of single group
      comparisons (P < 0.05, significant). RESULTS: The image quality of the structures
      evaluated in the DR images with a grid was significantly higher than that
      obtained without a grid (P < 0.001) for all structures. The use of a grid in CR
      significantly improved the overall image quality, lung parenchyma, and soft
      tissue delineation (P < 0.001). Foreign body delineation, however, was
      significantly better in the CR images obtained without a grid (P < 0.001),
      whereas the 2 systems showed no significant difference regarding thoracic spine
      delineation (P = 0.554). The scores of the DR images were significantly higher
      than those of the CR images for all structures. The interobserver agreement was
      substantial for lung parenchyma (ICC, 0.77), soft tissue (ICC, 0.78), thoracic
      spine (ICC, 0.80), and the overall image quality (ICC, 0.78) and was almost
      perfect for foreign bodies (ICC, 0.81). CONCLUSIONS: The use of an antiscatter
      grid significantly improved the image quality of bedside DR radiographs. A
      similar effect was seen with CR radiographs but only for lung parenchyma, soft
      tissue, and the overall image quality. Mobile DR outperformed CR in all
      structures.

PMID- 24019020
TI  - Clinical comparison between a currently available single-loop and an
      investigational dual-channel endorectal receive coil for prostate magnetic
      resonance imaging: a feasibility study at 1.5 and 3 T.
AB  - OBJECTIVES: The objectives of this study were to test the feasibility of an
      investigational dual-channel next-generation endorectal coil (NG-ERC) in vivo, to
      quantitatively assess signal-to-noise ratio (SNR), and to get an impression of
      image quality compared with the current clinically available single-loop
      endorectal coil (ERC) for prostate magnetic resonance imaging at both 1.5 and 3
      T. MATERIALS AND METHODS: The study was approved by the institutional review
      board, and written informed consent was obtained from all patients. In total, 8
      consecutive patients with prostate cancer underwent a local staging magnetic
      resonance examination with the successive use of both coils in 1 session (4
      patients at 1.5 T and 4 other patients at 3 T). Quantitative comparison of both
      coils was performed for the apex, mid-gland and base levels at both field
      strengths by calculating SNR profiles in the axial plane on an imaginary line in
      the anteroposterior direction perpendicular to the coil surface. Two radiologists
      independently assessed the image quality of the T2-weighted and apparent
      diffusion coefficient maps calculated from diffusion-weighted imaging using a 5
      point scale. Improvement of geometric distortion on diffusion-weighted imaging
      with the use of parallel imaging was explored. Statistical analysis included a
      paired Wilcoxon signed rank test for SNR and image quality evaluation as well as
      kappa statistics for interobserver agreement. RESULTS: No adverse events were
      reported. The SNR was higher for the NG-ERC compared with the ERC up to a
      distance of approximately 40 mm from the surface of the coil at 1.5 T (P < 0.0001
      for the apex, the mid-gland, and the base) and approximately 17 mm (P = 0.015 at
      the apex level) and 30 mm at 3 T (P < 0.0001 for the mid-gland and base). Beyond
      this distance, the SNR profiles of both coils were comparable. Overall, T2
      weighted image quality was considered better for NG-ERC at both field strengths.
      Quality of apparent diffusion coefficient maps with the use of parallel imaging
      was rated superior with the NG-ERC at 3 T. CONCLUSIONS: The investigational NG
      ERC for prostate imaging outperforms the current clinically available ERC in
      terms of SNR and is feasible for continued development for future use as the next
      generation endorectal coil for prostate imaging in clinical practice.

PMID- 24019021
TI  - Histological specificity of alterations and expression of KIT and KITLG in non
      small cell lung carcinoma.
AB  - Characterization of molecules within important oncogenetic pathways may have
      future implications for development of therapies and biomarkers in lung cancer.
      One such target is the tyrosine kinase receptor KIT (c-KIT). We evaluated
      alterations and expression of KIT and its ligand, KITLG (also known as SCF), in
      72 clinical lung tumor specimens of different histologies. Gene copy number, mRNA
      expression levels, and protein expression were assayed using array-based
      comparative genomic hybridization, real-time quantitative reverse transcription
      PCR and immunohistochemistry, respectively. For validation, we investigated copy
      number alterations and mRNA expression in external microarray data sets of 1,600
      and 555 primary lung tumors, respectively. Positivity for KIT staining was most
      common in large cell neuroendocrine carcinoma (LCNEC) which also showed the
      highest KIT mRNA expression levels whereas expression was lowest in squamous cell
      carcinoma (SqCC). KIT mRNA expression levels were higher in KIT immunopositive
      samples, but expression was not affected by KIT copy numbers. Copy number gains
      of KIT were significantly more frequent in SqCC compared with adenocarcinoma in
      our own series and in the 1,600-sample data set. Immunopositivity for both KIT
      and KITLG in the same tumor was rare except in LCNEC. Our results highlight an
      increased KIT mRNA expression and frequent KIT immunopositivity in LCNEC but
      point out a poor correlation between KIT copy numbers and expression in SqCC,
      perhaps reflecting the existence of a protective mechanism against KIT
      alterations in this subgroup.

PMID- 24019023
TI  - Compartmental models for apical efflux by P-glycoprotein--part 1: evaluation of
      model complexity.
AB  - PURPOSE: With the goal of quantifying P-gp transport kinetics, Part 1 of these
      manuscripts evaluates different compartmental models and Part 2 applies these
      models to kinetic data. METHODS: Models were developed to simulate the effect of
      apical efflux transporters on intracellular concentrations of six drugs. The
      effect of experimental variability on model predictions was evaluated. Several
      models were evaluated, and characteristics including membrane configuration,
      lipid content, and apical surface area (asa) were varied. RESULTS: Passive
      permeabilities from MDCK-MDR1 cells in the presence of cyclosporine gave lower
      model errors than from MDCK control cells. Consistent with the results in Part 2,
      model configuration had little impact on calculated model errors. The 5
      compartment model was the simplest model that reproduced experimental lag times.
      Lipid content and asa had minimal effect on model errors, predicted lag times,
      and intracellular concentrations. Including endogenous basolateral uptake
      activity can decrease model errors. Models with and without explicit membrane
      barriers differed markedly in their predicted intracellular concentrations for
      basolateral drug exposure. Single point data resulted in clearances similar to
      time course data. CONCLUSIONS: Compartmental models are useful to evaluate the
      impact of efflux transporters on intracellular concentrations. Whereas a 3
      compartment model may be sufficient to predict the impact of transporters that
      efflux drugs from the cell, a 5-compartment model with explicit membranes may be
      required to predict intracellular concentrations when efflux occurs from the
      membrane. More complex models including additional compartments may be
      unnecessary.

PMID- 24019022
TI  - FRAP in pharmaceutical research: practical guidelines and applications in drug
      delivery.
AB  - Fluorescence recovery after photobleaching (FRAP) is a fluorescence microscopy
      technique that has attracted a lot of interest in pharmaceutical research during
      the last decades. The main purpose of FRAP is to measure diffusion on a
      micrometer scale in a non-invasive and highly specific way, making it capable of
      measurements in complicated biomaterials, even in vivo. This has proven to be
      very useful in the investigation of drug diffusion inside different tissues of
      the body and in materials for controlled drug delivery. FRAP has even found
      applications for the improvement of several medical therapies and in the field of
      diagnostics. In this review, an overview is given of the different applications
      of FRAP in pharmaceutical research, together with essential guidelines on how to
      perform and analyse FRAP experiments. 

PMID- 24019025
TI  - Anion dependent self-assembly of a linear hexanuclear Yb(III) salen complex with
      enhanced near-infrared (NIR) luminescence properties.
AB  - Reactions of H2salen (H2L, N,N'-ethylene bis(salicylideneimine)) with
      Yb(CF3SO3)3, Yb(OAc)34H2O and Yb(NO3)36H2O in MeOH-EtOH under reflux gave NIR
      luminescent complexes [Yb6L9(H2L)2] (1), [Yb3L3(HL)(OH)2] (2) and
      [Yb2L2(H2L)2(NO3)(MeOH)2]NO3 (3), respectively.

PMID- 24019024
TI  - Complexation of cell-penetrating peptide-polymer conjugates with polyanions
      controls cells uptake of HPMA copolymers and anti-tumor activity.
AB  - PURPOSE: Cell penetrating peptides (CPPs) can mediate effective delivery of their
      associated drugs and drug carriers intracellularly, however their lack of cell
      specificity remains a major obstacle for their clinical development. We aimed at
      improving the cell specificity and therapeutic efficacy of HPMA copolymer
      octaarginine (R8) conjugate (P-R8) in cells at the tumor micro-environment.
      METHODS: To avoid premature cell-penetration, the positively charged R8 moieties
      were masked via electrostatic complexation with various polyanionic molecules
      (heparin sulfate, hyaluronic acid, fucoidan and poly-glutamic acid). We followed
      the kinetics of the FITC-labeled P-R8 penetration into endothelial and cancer
      cells over-time after its complexation in vitro and further tested whether the in
      situ addition of a stronger polycation can trigger the release of P-R8 from the
      complexes to resume cell penetration activity. A murine model of B16-F10 lung
      metastasis was then used as an in vivo model for assessing the therapeutic
      efficacy of the P-R8, loaded with doxorubicin (P-R8-DOX), after its complexation
      with PGA. RESULTS: The intracellular penetration of P-R8-FITC was reversibly
      inhibited by forming electrostatic interactions with counter polyanions, and can
      be restored either gradually over time by dissociation from the polyanions, or
      promptly following the addition of protamine sulfate. Mice injected with B16-F10
      cells and treated with P-R8-DOX/PGA complexes, exhibited a significant prolonged
      survival times when compared with DOX-treated mice or relative to mice treated
      with either P-R8-DOX or P-DOX alone. CONCLUSIONS: The gradual release of P-R8
      from P-R8-DOX/PGA may improve the therapeutic efficacy of water-soluble based
      nanomedicines for the treatment of solid lung tumors.

PMID- 24019026
TI  - Real-time DNP NMR observations of acetic acid uptake, intracellular
      acidification, and of consequences for glycolysis and alcoholic fermentation in
      yeast.
AB  - Uptake and upshot in vivo: Straightforward methods that permit the real-time
      observation of organic acid influx, intracellular acidification, and concomitant
      effects on cellular-reaction networks are crucial for improved bioprocess
      monitoring and control. Herein, dynamic nuclear polarization (DNP) NMR is used to
      observe acetate influx, ensuing intracellular acidification and the metabolic
      consequences on alcoholic fermentation and glycolysis in living cells.

PMID- 24019027
TI  - The behavioral and endocrinological development of stress response in dogs.
AB  - Endocrinological stress response has been shown to be absent in a specific period
      of the early life of rodents; this is named the stress-hyporesponsive period
      (SHRP). The SHRP is a significant period for the appropriate development of
      infants. In this study, the presence of SHRP in dogs was identified by conducting
      a 5-min separation test in 142 Labrador retriever puppies in their early
      socialization period and measuring the changes in urinary cortisol levels. An
      increase in cortisol after separation was found after 5 weeks of age, suggesting
      that the SHRP persists until 4 weeks of age in dogs. The distress vocalization
      during separation changed and the lactating behavior decreased rapidly around 5
      weeks of age, suggesting that the endocrinological and emotional aspects of
      development change at approximately 5 weeks of age and maternal inhibition of
      cortisol might occur in dogs as well as rodents.

PMID- 24019028
TI  - Ligand exchange in ionic systems and its effect on silver nucleation and growth.
AB  - The electrodeposition of metals from ionic solutions is intrinsically linked to
      the reactivity of the solute ions. When metal salts dissolve, the exchange of the
      anion with the molecular and ionic components from solution affects the
      speciation and therefore the characteristics of metal reduction. This study
      investigates the nucleation mechanism, deposition kinetics, metal speciation and
      diffusion coefficients of silver salts dissolved in Deep Eutectic Solvents. The
      electrochemical reduction of AgCl, AgNO3 and Ag2O is studied in 1 : 2 choline
      chloride : ethylene glycol and 1 : 2 choline chloride : urea. Cyclic voltammetry
      is used to evaluate electrochemical kinetics. Detailed analysis of
      chronoamperometric data shows that silver deposits form via multiple 3D
      nucleation with mass transport controlled hemispherical growth. The nucleation
      mechanism was found to be potential dependent, varying from progressive to
      instantaneous as the reduction potential becomes more cathodic. Diffusion
      coefficients are determined using three different methods. Trends are
      rationalised in terms of solvent viscosity and silver speciation analysis with
      EXAFS. The morphology of electroreduced silver is investigated with scanning
      electron microscopy and shows that deposits from the urea based liquid form more
      dense morphologies than those from the ethylene glycol based liquid. 

PMID- 24019029
TI  - Tolerance to cocaine's effects following chronic administration of a dose without
      detected effects on response rate or pause.
AB  - To observe tolerance to drug effects on operant behavior, the dose that
      researchers have often selected for chronic administration is one that disrupts,
      but does not abolish, responding. Some evidence suggests that tolerance may
      develop after chronic administration of relatively smaller doses. The purpose of
      the present experiment was to assess systematically effects of chronic
      administration of a dose without detected effect on responding. Specifically,
      response rates and post-reinforcement pauses of five pigeons key pecking under a
      three-component multiple fixed-ratio schedule of food reinforcement were observed
      under chronic cocaine administration. We evaluated the effects of a range of
      doses (1.0 mg/kg to 17.0  mg/kg) during acute administration. The largest dose
      that failed to alter responding acutely then was administered chronically (1.0 
      mg/kg for 1 pigeon, 3.0  mg/kg for 3 pigeons, and 5.6  mg/kg for 1 pigeon). After
      30 consecutive sessions of chronic administration, smaller and larger doses
      occasionally were substituted for the chronic dose. Pigeons then received pre
      session saline administration for 30 consecutive sessions, and the post-chronic
      effects of the series of doses on responding were determined. All subjects
      developed tolerance to doses of cocaine that initially had caused large decreases
      in rate, with the magnitude of the effects varying across components of the
      multiple schedule and subjects. Specifically, tolerance generally was greatest in
      the components with smaller ratios. Following post-chronic saline administration,
      tolerance was usually diminished. Overall, the results demonstrate that under
      these conditions, repeated experience with disruptive effects of cocaine on food
      maintained responding is not a necessary factor in the development of tolerance.

PMID- 24019030
TI  - Adjustment of measures of strength and power in youth male athletes differing in
      body mass and maturation.
AB  - Adjustment for body mass and maturation of strength, power, and velocity measures
      of young athletes is important for talent development. Seventy-four youth male
      athletes performed a ballistic leg press test at five loads relative to body
      mass. The data were analyzed in maturity groups based on years from peak height
      velocity: -2.5 to -0.9 y (n = 29); -1.0 to 0.4 y (n = 28); and 0.5 to 2.0 y (n =
      16). Allometric scaling factors representing percent difference in performance
      per percent difference in body mass were derived by linear regression of log
      transformed variables, which also permitted adjustment of performance for body
      mass. Standardized differences between groups were assessed via magnitude-based
      inference. Strength and power measures showed a greater dependency on body mass
      than velocity-related variables (scaling factors of 0.56-0.85 vs. 0.42-0.14%/%),
      but even after adjustment for body mass most differences in strength and power
      were substantial (7-44%). In conclusion, increases in strength and power with
      maturation are due only partly to increases in body mass. Such increases, along
      with appropriate adjustment for body mass, need to be taken into account when
      comparing performance of maturing athletes. 

PMID- 24019031
TI  - Heparin sensing and binding - taking supramolecular chemistry towards clinical
      applications.
AB  - Heparin is a vital biomolecule in widespread clinical use as an anti-coagulant.
      Heparin sensors have potential applications in the bedside detection of heparin
      levels in human blood during surgery, while high-affinity heparin binders may
      enable the development of effective heparin reversal agents for use in patients
      once surgery is complete. However, human blood is a challenging medium in which
      to achieve selective high-affinity molecular recognition, and as such, this
      system provides a fascinating challenge to supramolecular chemists. This has
      encouraged research using a variety of different systems and is stimulating new
      approaches to the application of molecular recognition. This review article
      provides an overview of research from both clinical and supramolecular
      communities towards heparin binding and sensing and considers how this area may
      develop in the future. 

PMID- 24019032
TI  - Dyslipidaemia: PCSK9 antibodies: a dividend of the genomics revolution.

PMID- 24019033
TI  - Evolving views on protein palmitoylation (Comment on DOI 10.1002/bies.201300076).

PMID- 24019034
TI  - Alternative and complementary medicine in our hospitals: forbidden yesterday,
      tolerated today... implemented tomorrow?

PMID- 24019035
TI  - SEOM guide to antiemetic prophylaxis in cancer patients treated with chemotherapy
      2013.
AB  - Chemotherapy-induced emesis (CIE) both in the form of nausea and vomiting is one
      of the adverse effects most feared by patients who receive treatment, and one of
      the factors that most affect their quality of life and limit their functional
      capacity for everyday activities. Chemotherapy-induced emesis can result from
      many factors, depending on the treatment and the patients themselves. The best
      treatment for CIE is prevention, based on the use of drugs aimed at inhibiting
      the signal of certain neurotransmitters involved in the process. Antiemetic
      prophylaxis for chemotherapy of high-emetogenous potential lasting 1 day includes
      a combination of anti-5-HT3, neurokinin-1 inhibitors and dexamethasone.
      Antiemetic prophylaxis for chemotherapy of moderate-emetogenous potential lasting
      1 day includes a combination of palonosetron and dexamethasone. Prophylaxis is
      not recommended for chemotherapy with minimal emetogenous potential. In the case
      of unforeseen or refractory emesis the use of olanzapine, metoclopramide or
      phenothiazine should be considered.

PMID- 24019036
TI  - Recommendations of a group of experts for the pathological assessment of tumour
      regression of liver metastases of colorectal cancer and damage of non-tumour
      liver tissue after neoadjuvant therapy.
AB  - Colorectal cancer (CRC) incidence has increased during the past decades in Spain,
      being the first malignant tumour in incidence. Observed mortality for CRC is
      mainly due to liver and lung metastases. The only curative treatment is surgery;
      new surgical techniques and neoadjuvant treatments have increased the number of
      surgery candidate patients. Patients should be managed with a multidisciplinary
      approach that includes imaging techniques, chemotherapy, surgery and pathological
      assessment. As an answer to this approach, a group of pathology experts
      interested on CRC liver metastases aimed to review the diagnosis and prognosis of
      liver mestastases and developed practical recommendations for its assessment. The
      expert group revised the current literature and prepared questions to be
      discussed based on available evidence and on their clinical practise. As a
      result, recommendations for the assessment of tumour regression of liver
      metastases are proposed, which could be implemented in oncology centres allowing
      assessment standardisation for these patients. Prospective multi-center studies
      to evaluate these recommendations validity will further contribute to improve the
      standard care of CRC liver metastases patients. 

PMID- 24019037
TI  - Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with
      non-small cell lung cancer.
AB  - PURPOSE: Emerging evidences indicate that dysregulated microRNAs are implicated
      in cancer tumorigenesis and progression. MicroRNA-9 (miR-9) has various
      expression patterns in diverse human cancers. However, its clinical significance
      in human non-small cell lung cancer has not yet been elucidated. In the present
      study, we detected the expression of miR-9 in non-small cell lung cancer and
      adjacent noncancerous tissues and explored its relationships with
      clinicopathological characteristics and prognosis. METHODS: Expression levels of
      miR-9 in 116 pairs of non-small cell lung cancer and adjacent normal tissues were
      detected by real-time quantitative RT-PCR assay. To determine its prognostic
      value, overall survival (OS) and progression-free survival (PFS) were evaluated
      using the Kaplan-Meier method. Univariate and multivariate analysis were
      performed using the Cox proportional hazard analysis. RESULTS: MiR-9 expression
      in non-small cell lung cancer tissues was significantly higher than that in
      adjacent normal tissues (p = 0.001), and its up-regulation was significantly
      correlated to advanced tumor-node-metastasis (TNM) stage (p < 0.001), tumor size
      (p = 0.013), and lymph node metastasis (p = 0.001). Furthermore, Kaplan-Meier
      analysis demonstrated that high miR-9 expression clearly predicted poorer PFS (p
      < 0.001) and OS (p < 0.001). In the multivariate analysis, increased miR-9
      expression was an independent prognostic factor for both PFS (p = 0.002) and OS
      (p = 0.013). CONCLUSIONS: MiR-9 was up-regulated in non-small cell lung cancer
      tissues and correlated with adverse clinical features and unfavorable survival,
      indicating that miR-9 might be involved in non-small lung cancer progression and
      could serve as a promising biomarker for further risk stratification in the
      treatment of this cancer.

PMID- 24019038
TI  - Traumatic brain injury and chronic traumatic encephalopathy: a forensic
      neuropsychiatric perspective.
AB  - Recent scientific reports and popular press describing chronic traumatic
      encephalopathy (CTE) collectively link this condition to a broad array of
      neuropsychiatric symptoms, including extremely rare and multi-determined
      behaviors such as murder-suicide. These reports are difficult to reconcile with
      several decades of research on the science of traumatic brain injury (TBI) and
      its consequences, especially the natural history and prognosis of mild TBI. This
      article attempts to reconcile these sources by reviewing the state of the science
      on CTE, with particular attention to case definitions and neuropathological
      criteria for this diagnosis. The evidence for links between TBI, CTE, and
      catastrophic clinical events is explored, and the complexity of attributing rare
      frequency behavioral events to CTE is highlighted. The clinical and medicolegal
      implications of the best available evidence are discussed, concluding with a
      cautionary note against prematurely generalizing current findings on CTE to
      entire populations of persons with, or at risk for, concussion exposures.

PMID- 24019039
TI  - Association between undervaccination with diphtheria, tetanus toxoids, and
      acellular pertussis (DTaP) vaccine and risk of pertussis infection in children 3
      to 36 months of age.
AB  - IMPORTANCE: Undervaccination is an increasing trend that potentially places
      children and their communities at an increased risk for serious infectious
      diseases. OBJECTIVE: To examine the association between undervaccination and
      pertussis in children 3 to 36 months of age. DESIGN: Matched case-control study
      with conditional logistic regression analysis. SETTING: Eight managed care
      organizations of the Vaccine Safety Datalink between 2004 and 2010. PARTICIPANTS:
      Each laboratory-confirmed case of pertussis (72 patients) was matched to 4
      randomly selected controls (for a total of 288 controls). The case patients were
      matched to controls by managed care organization site, sex, and age at the index
      date. The index date was defined as the date of pertussis diagnosis for the case
      patients. EXPOSURE: Undervaccination for the diphtheria, tetanus toxoids, and
      acellular pertussis (DTaP) vaccine. Undervaccination was defined as the number of
      doses of DTaP vaccine that was either missing or delayed by the index date. Case
      patients and controls could be undervaccinated by 0, 1, 2, 3, or 4 doses of DTaP
      vaccine. Children undervaccinated by 0 doses were considered age-appropriately
      vaccinated by the index date. MAIN OUTCOME AND MEASURE: Pertussis. RESULTS: Of
      the 72 case patients with pertussis, 12 (16.67%) were hospitalized, and 34
      (47.22%) were undervaccinated for DTaP vaccine by the date of pertussis
      diagnosis. Of the 288 matched controls, 64 (22.22%) were undervaccinated for DTaP
      vaccine. Undervaccination was strongly associated with pertussis. Children
      undervaccinated for 3 or 4 doses of DTaP vaccine were 18.56 (95% CI, 4.92-69.95)
      and 28.38 (95% CI, 3.19-252.63) times more likely, respectively, to have received
      a diagnosis of pertussis than children who were age-appropriately vaccinated.
      CONCLUSIONS AND RELEVANCE: Undervaccination with DTaP vaccine increases the risk
      of pertussis among children 3 to 36 months of age.

PMID- 24019040
TI  - A general strategy for the synthesis of P-stereogenic compounds.
AB  - A great leap forward toward the general synthesis of P-stereogenic compounds:
      Heating H3 PO2 with (-)-menthol and paraformaldehyde gives easily crystallized
      menthyl hydroxymethyl-H-phosphinate (1). From this product, virtually any P
      stereogenic compound can be synthesized. 

PMID- 24019041
TI  - Optimal lymphadenectomy for esophageal adenocarcinoma.
AB  - Recently published data have shown that an extended lymphadenectomy during the en
      bloc esophagectomy leads to a significant increased long-term survival for
      esophageal adenocarcinoma. On the other hand some studies indicate that the
      increased survival is based on stage migration and that the surgical complication
      rate is increased after extended lymphadenectomy. The aim of this review was to
      give an overview about all aspects of an extended lymphadenectomy in patients
      with esophageal adenocarcinoma. The review of the literature shows clearly that
      the number of involved lymph nodes is an independent prognostic factor in
      patients with esophageal adenocarcinoma. Furthermore, an extended lymphadenectomy
      leads to an increased long-term survival. Some studies describe that 23 lymph
      nodes should be removed to predict survival; other studies 18 lymph nodes or 15
      lymph nodes. Opponents indicate that the survival benefit is based on stage
      migration. The studies with a large study population have performed a Cox
      regression analyzes and identified the number of lymph nodes removed as an
      independent factor for improved survival, which means it is significant
      independently from other parameters. Under these circumstances is stage migration
      not an option to explain the survival benefit. An important difficulty is, that
      there is no standardized definition of an extended lymphadenectomy, which means
      the localization and number of removed lymph nodes differ depending from the
      performing centre. The controversies regarding the survival benefit of the
      lymphadenectomy is based on the lack of standardisation of the lymphadenectomy.
      The main goal of further studies should be to generate a clear definition of an
      extended lymphadenectomy in patients with esophageal adenocarcinoma. 

PMID- 24019042
TI  - Avoiding complications in esophageal cancer surgery.
AB  - Modern handling of esophageal cancer patients is based on a multidisciplinary
      concept, but surgery remains the primary curative treatment modality.
      Improvements in the perioperative care have reduced the overall morbidity and
      mortality, but 2-7% of the patients may still die within 30 days as a direct
      consequence of complications related to the esophagectomy procedure. Primarily
      based on results from randomized studies published after 2000 this review
      describes some of the factors that may contribute to the development of
      postoperative complications following esophageal cancer surgery as well as
      studies intended to finding ways of reducing the complication rate. 

PMID- 24019043
TI  - The emerging role of salvage esophagectomy.
AB  - The role of surgery and other treatment options for esophageal cancer continue to
      evolve. As more patients receive definitive chemoradiotherapy, salvage
      esophagectomy has emerged as an important treatment for local and regional
      failure. Although initial reports found high morbidity and mortality, more recent
      studies have found improvements in both perioperative complications and long term
      survival following salvage resection. We review the emerging role of salvage
      esophagectomy. 

PMID- 24019044
TI  - Percutaneous radiofrequency ablation versus surgical radiofrequency-assisted
      nodulectomy in treatment of small single nodes of hepatocellular carcinoma: our
      experience.
AB  - AIM: Surgical resection usually represents the treatment of choice for solitary
      hepatocellular carcinoma (HCC) in cirrhotic patients, with well preserved liver
      function; local ablative strategies are the best treatment option for patients
      with small tumors who are not candidates for surgical resection or liver
      transplantation. Several studies showed that percutaneous radiofrequency ablation
      (RFA) has similar efficacy to surgical nodulectomy in the treatment of early
      stage HCC, and is associated with lower complication rates and costs than
      resection. The aim of this study was to compare the effectiveness of these
      treatments, in terms of morbidity, overall survival, tumor recurrence and causes
      of death. METHODS: Between January 2006 and January 2012 we observed 176 patients
      affected by HCC, 84 underwent curative treatment. The 40 patients presenting
      single HCC nodes smaller than 3 cm in diameter have been treated with
      radiofrequency-assisted surgical nodulectomy (N.=20) or with percutaneous
      radiofrequency (N.=20). RESULTS: No perioperative mortality occurred in the two
      groups. Perioperative morbidity was 5% in group A (1 case of peritoneal bleeding)
      and 5% in group B (1 case of hepatic abscess). Disease-free survival was slightly
      higher in surgically treated patients, but not statistically significative
      differences have been demonstrated (P<0.06); no local recurrences were observed
      in surgically treated patients. CONCLUSION: RF and surgical nodulectomy can be
      either used in treatment of early stage hepatocellular carcinoma; no differences
      in terms of morbidity, overall and disease free survival were observed;
      nodulectomy seems to prevent from tumor local recurrence.

PMID- 24019045
TI  - Laparoscopic adrenalectomy for Cushing's syndrome: a 12-year experience.
AB  - AIM: The outcome after laparoscopic adrenalectomy in 51 patients with pre
      Cushing's and Cushing's syndrome was evaluated at six months and one year of
      follow-up. METHODS: In this retrospective analysis of 51 patients (35 females and
      16 males) selected for laparoscopic adrenalectomy (28 left and 23 right adrenal
      glands), clinical presentation, endocrine and blood chemistry and hemodynamics,
      and pre- and postsurgical management were analyzed. Evaluations included, blood
      pressure, body-mass index (BMI), lipid profile, blood glucose (fasting insulin
      and oral glucose tolerance test [OGTT]), liver function and hormonal profile (17
      hydroxyprogesterone, dehydroepiandrosterone sulfate and cortisol), and
      perioperative complications. RESULTS: Follow-up assessment showed a significant
      reduction in systolic (12.34 mm Hg) and diastolic blood pressure (11.09 mm Hg), a
      statistically significant decrease in total (11.67 mg/dL) and a statistically
      significant increase in high-density lipoprotein (HDL) cholesterol (6.46 mg/dL),
      and a statistically significant decrease in blood glucose at 60 minutes and an
      increase in insulin at 120 minutes. No statistically significant changes in the
      hormone profile were observed. There was a statistically significant reduction in
      cortisol concentration in response to the dexamethasone test. Mortality was zero
      and the surgical complications rate was low. CONCLUSION: Laparoscopic
      adrenalectomy has become the gold standard in the treatment of adrenal disease.
      It is a safe technique, with clinically effective results and an excellent
      perioperative course.

PMID- 24019046
TI  - Gastric emptying after sleeve gastrectomy: statistical evidence of a controlled
      prospective study with gastric scintigraphy.
AB  - AIM: Laparoscopic sleeve gastrectomy (LSG) is a stand-alone bariatric procedure,
      its feasibility and efficacy being confirmed by long-term data. The effect of the
      procedure is believed to be based on the gastric restriction and reduction of
      ghrelin. Nevertheless it remains still controversial the role of LSG on gastric
      emptying and the impact that this may have on weight loss outcomes. Our aim is to
      assess gastric emptying after LSG using gastric scintigraphy. METHODS: For this
      prospective randomized study, 45 patients undergoing LSG at our Centre for the
      Multidisciplinary Treatment of Severe Obesity from April 2009 to April 2011 were
      enrolled and observed prospectively (Group A). The inclusion criteria followed
      the guidelines for bariatric surgery. All patients performed gastric emptying
      scintigraphy through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc
      99. Group A performed the exam before (A1) and after the operation (A2). A
      control group (Group B) included 20 patients undergoing scintigraphic assessment
      for other reasons. RESULTS: LSG was performed following a standardized technique.
      No complications were observed. The scintigraphic study showed a reduced half
      life tracer (A1 vs. A2: 80.4+/-16.5 min vs. 64.3+/-22 min P=0.06), without a
      significant difference. Comparing the two groups no differences occurred before
      operation (B vs. A1). Gastric emptying time resulted significatively reduced in
      group A2 rather than in group A1 and B. CONCLUSION: Gastric motility plays a role
      in the pathogenesis of obesity. Our experience suggests that LSG reduces gastric
      emptying time, but further studies are necessary to reach statystical
      significativity.

PMID- 24019047
TI  - Evaluation of necessity for mechanical bowel preparation before Milligan-Morgan
      hemorrhoidectomy: a randomized prospective clinical study.
AB  - AIM: In this randomized prospective clinical study, we aimed to evaluate the
      effect of mechanical bowel preparation (MBP) before Milligan-Morgan
      hemorrhoidectomy on intraoperative procedures and postoperative complication
      rates to determine whether MBP is adventageous or not before elective anorectal
      surgeries. METHODS: Forty patients who had internal grade III or IV hemorrhoidal
      disease and who would underwent open hemorrhoidectomy were randomized into two
      groups: non-MBP group (female:male, 11:9; mean age, 33.8+/-9.57 years) that would
      not receive MBP before the surgery, and MBP group (female:male, 12:8; mean age,
      34.7+/-11.37 years) that would be given one Fleet enema on the morning of
      Milligan-Morgan hemorrhoidectomy. Intraoperative variables and postoperative
      complications were compared between two groups. RESULTS: MPB had no effect on
      both intraoperative and postoperative variables, such as operating time,
      intraoperative bleeding, visual analogue scale (VAS) score for the comfort of the
      surgeon during operation, the presence of stool or enema remnants in anal canal,
      the presence of mucosal edema of the anal canal intraoperatively, the rates of
      postoperative bleeding and infection, VAS score for the pain on third day
      postoperatively, time to first stool after the operation, VAS score for the pain
      during first stool after the operation, and number of analgesics during one week
      postoperatively (P>0.05 for all). CONCLUSION: MBP performed before surgery does
      not provide introperative or postoperative benefit for Milligan-Morgan
      hemorrhoidectomy, thus MBP is not necessary before elective anorectal surgeries.

PMID- 24019048
TI  - A comparative study of the retention or removal of jejunal mucosa during
      pancreatic duct to jejunal anastomosis.
AB  - AIM: The aim of this study was to compare the two anastomosis methods, that is,
      the retention or the removal of the jejunal mucosa during pancreatic duct to
      jejunal anastomosis after pancreaticoduodenectomy (PD). METHODS: For this
      purpose, 46 PD patients were randomly and equally divided into groups A and B. In
      group A, the remnant pancreas was inserted 3 cm into the jejunum and the
      connecting part was sutured. In group B, the jejunal mucous membrane was
      cauterized 3 cm at the end, the remnant pancreas was sutured with the jejunal
      muscle layer, and the jejunum and pancreas were sutured together. RESULTS: We
      found that in group A, the reoperation rate due to delayed bleeding was 13%
      (3/23) and the ulcer bleeding around anastomosis was 4.3% (1/23). In group B, the
      reoperation rate due to bleeding was 4.3% (1/23) and the incidence of
      postoperative pancreatic fistula was 17.4% (4/23). The duration of
      pancreaticojejunostomy operation in group A (46 +/- 0.34 min) was shorter than in
      group B (P<0.001). CONCLUSION: We, therefore, concluded that the pancreatic duct
      to jejunal anastomosis with retained jejunal mucosa was a simple and easy to
      perform method while it also excluded the risk of postoperative pancreatic
      fistula formation.

PMID- 24019049
TI  - Effect of surgery treatment on hypersplenism caused by cirrhotic portal
      hypertension.
AB  - AIM: Aim of the study was to summarize the types and quantities of peripheral
      hematocytopenia in the patients of hypersplenism caused by cirrhotic portal
      hypertension and investigate the effect of surgery, including splenectomy on the
      patient's peripheral blood cells and liver function. METHODS: The quantities of
      peripheral blood cells in the 322 patients of hypersplenism, caused by cirrhotic
      portal hypertension, were retrospectively studied. Then, the preoperative and
      postoperative values of peripheral blood cells and liver function were compared
      in 266 patients who were followed up. The liver function was scored and graded
      according to Child-Pugh scoring system. RESULTS: The study enrolled 322 patients
      who showed hematocytopenia, including multi-hemocyte decrease in 206 patients
      (64%) and simple hemocyte decrease in 116 patients (36%). After surgical
      treatment in the 226 patients who were followed up, the quantities of peripheral
      blood cells significantly increased (P<0.01), Child-Pugh grade A increased by 32
      patients (14.2%), while Child-Pugh grade C increased only by 2 patients (0.9%),
      the liver function scores decreased (P<0.05). CONCLUSION: Hypersplenism caused by
      cirrhotic portal hypertension mainly manifests as a multi-hemocyte decrease and
      rarely shows single types of hematocytopenia. Surgical intervention including
      splenectomy can increase the reduction of hemocytes and promote the recovery of
      liver function.

PMID- 24019050
TI  - [Indication on the use of temporary ileostomy in extraperitoneal rectal surgery:
      is it still valid? Consideration on a case series].

PMID- 24019051
TI  - Is the routinely use of Tachosil(r) the answer to prevent anastomotic leakage in
      urgent abdominal surgery?

PMID- 24019052
TI  - An intervention to reduce postpartum depressive symptoms: a randomized controlled
      trial.
AB  - Depressive symptoms and depression are a common complication of childbirth, and a
      growing body of literature suggests that there are modifiable factors associated
      with their occurrence. We developed a behavioral educational intervention
      targeting these factors and successfully reduced postpartum depressive symptoms
      in a randomized trial among low-income black and Latina women. We now report
      results of 540 predominantly white, high-income mothers in a second randomized
      trial. Mothers in the intervention arm received a two-step intervention that
      prepared and educated mothers about modifiable factors associated with postpartum
      depressive symptoms (e.g., physical symptoms, low self-efficacy), bolstered
      social support, and enhanced management skills. The control arm received enhanced
      usual care. Participants were surveyed prior to randomization, 3 weeks, 3 months,
      and 6 months postpartum. Depressive symptoms were assessed using the Edinburgh
      Postnatal Depression Scale (EPDS of 10 or greater). Prevalence of depressive
      symptoms postpartum was unexpectedly low precluding detection of difference in
      rates of depressive symptoms among intervention versus enhanced usual care
      posthospitalization: 3 weeks (6.0 vs. 5.6 %, p = 0.83), 3 months (5.1 vs. 6.5 %,
      p = 0.53), and 6 months (3.6 vs. 4.6 %, p = 0.53). 

PMID- 24019053
TI  - Vision and air flow combine to streamline flying honeybees.
AB  - Insects face the challenge of integrating multi-sensory information to control
      their flight. Here we study a 'streamlining' response in honeybees, whereby
      honeybees raise their abdomen to reduce drag. We find that this response, which
      was recently reported to be mediated by optic flow, is also strongly modulated by
      the presence of air flow simulating a head wind. The Johnston's organs in the
      antennae were found to play a role in the measurement of the air speed that is
      used to control the streamlining response. The response to a combination of
      visual motion and wind is complex and can be explained by a model that
      incorporates a non-linear combination of the two stimuli. The use of visual and
      mechanosensory cues increases the strength of the streamlining response when the
      stimuli are present concurrently. We propose this multisensory integration will
      make the response more robust to transient disturbances in either modality. 

PMID- 24019054
TI  - Inappropriate prescribing: a systematic overview of published assessment tools.
AB  - BACKGROUND: Criteria to assess the appropriateness of prescriptions might serve
      as a helpful guideline during professional training and in daily practice, with
      the aim to improve a patient's pharmacotherapy. OBJECTIVE: To create a
      comprehensive and structured overview of existing tools to assess inappropriate
      prescribing. METHOD: Systematic literature search in Pubmed (1991-2013). The
      following properties of the tools were extracted and mapped in a structured way:
      approach (explicit, implicit), development method (consensus technique, expert
      panel, literature based), focused patient group, health care setting, and covered
      aspects of inappropriate prescribing. RESULTS: The literature search resulted in
      46 tools to assess inappropriate prescribing.Twenty-eight (61%) of 46 tools were
      explicit, 8 (17%) were implicit and 10 (22%) used a mixed approach. Thirty-six
      (78%) tools named older people as target patients and 10 (22%) tools did not
      specify the target age group. Four (8.5%) tools were designed to detect
      inappropriate prescribing in hospitalised patients, 9 (19.5%) focused on patients
      in ambulatory care and 6 (13%) were developed for use in long-term care. Twenty
      seven (59%) tools did not specify the health care setting. Consensus methods were
      applied in the development of 19 tools (41%), the others were based on either
      simple expert panels (13; 28%) or on a literature search (11; 24%). For three
      tools (7%) the development method was not described. CONCLUSION: This overview
      reveals the characteristics of 46 assessment tools and can serve as a summary to
      assist readers in choosing a tool, either for research purposes or for daily
      practice use.

PMID- 24019056
TI  - Cooperative catalysis: combining an achiral metal catalyst with a chiral Bronsted
      acid enables highly enantioselective hydrogenation of imines.
AB  - Asymmetric hydrogenation of imines leads directly to chiral amines, one of the
      most important structural units in chemical products, from pharmaceuticals to
      materials. However, highly effective catalysts are rare. This article reveals
      that combining an achiral pentamethylcyclopentadienyl (Cp*)-iridium complex with
      a chiral phosphoric acid affords a catalyst that allows for highly
      enantioselective hydrogenation of imines derived from aryl ketones, as well as
      those derived from aliphatic ones, with ee values varying from 81 to 98 %. A
      range of achiral iridium complexes containing diamine ligands were examined, for
      which the ligands were shown to have a profound effect on the reaction rate,
      enantioselectivity and catalyst deactivation. The chiral phosphoric acid is no
      less important, inducing enantioselection in the hydrogenation. The induction
      occurs, however, at the expense of the reaction rate. 

PMID- 24019057
TI  - Development of auditory event-related potentials in infants prenatally exposed to
      methadone.
AB  - Developmental features of the P2 auditory ERP in a change detection paradigm were
      examined in infants prenatally exposed to methadone. Opiate dependent pregnant
      women maintained on methadone replacement therapy were recruited during pregnancy
      (N = 60). Current and historical alcohol and substance use, SES, and psychiatric
      status were assessed with a maternal interview during the third trimester.
      Medical records were used to collect information regarding maternal medications,
      monthly urinalysis, and breathalyzer to confirm comorbid drug and alcohol
      exposures. Between birth and 4 months infant ERP change detection performance was
      evaluated on one occasion with the oddball paradigm (.2 probability oddball)
      using pure-tone stimuli (standard = 1 kHz and oddball = 2 kHz frequency) at
      midline electrode sites, Fz, Cz, Pz. Infant groups were examined in the following
      developmental windows: 4-15, 16-32, or 33-120 days PNA. Older groups showed
      increased P2 amplitude at Fz and effective change detection performance at P2 not
      seen in the newborn group. Developmental maturation of amplitude and stimulus
      discrimination for P2 has been reported in developing infants at all of the ages
      tested and data reported here in the older infants are consistent with typical
      development. However, it has been previously reported that the P2 amplitude
      difference is detectable in neonates; therefore, absence of a difference in P2
      amplitude between stimuli in the 4-15 days group may represent impaired ERP
      performance by neonatal abstinence syndrome or prenatal methadone exposure.

PMID- 24019055
TI  - Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin
      maintenance dose and explicating a new pharmacogenetic algorithm in South Indian
      population.
AB  - OBJECTIVE: To determine the influence of genetic polymorphisms on warfarin
      maintenance dose and to explicate an algorithm using the pharmacogenetic and
      clinical factors to determine the maintenance and/or starting dose of warfarin in
      South Indian patients receiving warfarin therapy. METHODS: Patients receiving
      stabilized warfarin therapy (n=257) were included in the study. Single nucleotide
      polymorphisms (SNPs) of CYP2C9 (rs1799853 and rs1057910), VKORC1 (rs9923231,
      rs7196161, rs2884737, rs9934438, rs8050894, rs2359612 and rs7294), CYP4F2
      (rs2108622) and GGCX (rs11676382) were genotyped by the quantitative real time
      PCR method. RESULTS: The mean daily maintenance dose of warfarin was found to be
      4.7 +/- 2.1 mg/day. Patients with the CYP2C9*1/*2, *1/*3 and *2/*3 variant
      genotypes required a 51.0 (2.8 mg), 60.9 (2.3 mg) and 62.2 % (2.2 mg) lower daily
      maintenance dose of warfarin, respectively, than those patients with the
      CYP2C9*1/*1 wild-type genotype (5.2 mg) (p<0.0001). The genetic variants of
      CYP2C9, VKORC1 and GGCX were associated with decreased warfarin dose, except for
      rs7196161, rs7294 and rs2108622 which were associated with an increased warfarin
      dose. Genetic variations of CYP2C9 (*2 and *3), VKORC1 (rs9923231, rs7294,
      rs9934438 and rs2359612), CYP4F2, GGCX and non-genetic factors such as age, body
      weight, clinical status (post mechanical valve replacement) could explain up to
      62.1 % of the overall variation (adjusted r (2) 60.2 %, p<0.0001) in warfarin
      maintenance dose. CONCLUSION: Genetic polymorphisms of CYP2C9, VKORC1, CYP4F2 and
      GGCX are important predictive factors of warfarin maintenance dose, and the
      developed algorithm will be useful to predict the required maintenance and/or
      starting warfarin dose in South Indian populations.

PMID- 24019058
TI  - Intramolecular C-C agostic complexes: C-C sigma interactions by another name.
AB  - In this comprehensive review the developments in the synthesis, characterization
      and reactivity of complexes (s-, d- and f-block) in which a C-C single bond
      interacts with a metal centre are discussed: so called C-CM agostic complexes.
      Such species are of significant interest with regard to structure and bonding,
      the activation of C-C single bonds and, thus, catalytic methods of C-C bond
      formation (or activation). Examples of C-C agostic complexes of early and later
      transition metals, actinides and group 1 metals are discussed, along with C-C
      agostic interactions in metallacyclobutanes. Examples of Si-Si???M, B-C???M and B
      B???M agostic interactions are also presented. Throughout, the structural,
      spectroscopic and computational markers that indicate the likely presence of a C
      C???M agostic interaction in a complex are highlighted.

PMID- 24019059
TI  - Synthesis and quantitative analysis of diastereomeric linked ester conjugates
      with remote stereocenters using high-field NMR and chiral HPLC.
AB  - A stereochemically safe high-yielding procedure for linking unprotected as well
      as protected hydroxycarboxylic acids to chiral secondary alcohols via glycolic
      acid linker is proposed. L-menthol has been linked with both enantiomers of
      mandelic, malic, and methoxyphenylacetic acid using bromo- or iodoacetyl group as
      a precursor of the glycolic acid linker. High-field nuclear magnetic resonance
      (NMR) and chiral high-performance liquid chromatography (HPLC) determination of
      high diastereomeric ratio (dr) (>99%) of the products bearing remote
      stereocenters was explored. Chiral HPLC allowed quantitation of the diastereomers
      up to dr 99.9/0.1. High-field NMR quantitation of the diastereomeric and parent
      alcoholic impurities in esters was demonstrated at the molar 0.3% and 0.03%
      levels, respectively. These analyses were done via comparison of integral
      intensities from major component (13)C satellites in (1)H or even in (13)C
      spectra to the (1)H or (13C signals of impurities. Despite lower sensitivity, the
      last option generally has much better selectivity. In this way the dynamic
      resolution is brought down by two orders.

PMID- 24019060
TI  - Blood electrolytes exhibit a strong influence on the mobility of artificial
      catalytic microengines.
AB  - The developments in biomedical sciences foresee the inclusion of self-propelled
      catalytic micromotors for in vivo therapeutic strategies in the near future. We
      show here that blood electrolytes, such as Na(+), K(+), Ca(2+), Cl(-), SO4(2-)
      and phosphates, decrease the mobility of the Pt catalyzed tubular microjets. This
      effect is significant and in many cases, the microjets are completely disabled at
      physiologically relevant concentrations of the ions. A strategy to counterbalance
      this negative influence is suggested. These findings have a strong influence in
      the field of bubble-propelled artificial micromotors, where applications in blood
      are often envisioned. 

PMID- 24019061
TI  - Acute effects of sled towing on sprint time in male youth of different maturity
      status.
AB  - The purpose of this study was to investigate the effect of 2.5, 5, 7.5, and 10%
      body mass load on resisted sled towing 30 meter sprint times in male youth
      athletes of different maturity status. A total of 35 athletes (19 prepeak-height
      velocity (PHV) and 16 mid/post-PHV) sprinted three times in an unloaded and each
      of the loaded conditions. The pre-PHV athletes were significantly slower (~33%; p
      < .05) than the more mature athletes across all loads (unloaded, 2.5, 5, 7.5, 10%
      body mass). Each incremental load (i.e., 2.5% body mass) was found to reduce 30 m
      sprint times by 3.70% (+/- 2.59) and 2.45% (+/- 1.48) for the pre- and mid/post
      PHV respectively. The slopes of the pre- (y = 0.09 x + 5.71) and mid/post (y =
      0.04 x + 4.38) regression equations were compared and found to be statistically
      different (p = .004) suggesting that athletes of different maturity status
      responded differentially to the same relative resisted sprint load. Ten percent
      body mass load resulted in a reduced sprint time of ~15.8 and ~9.8% for the pre-
      and mid/post-PHV group, respectively. These results enable predictive equations
      to be formulated and appropriate resisted sprint loading, based on the intended
      focus of a session. 

PMID- 24019062
TI  - Systems factorial technology with R.
AB  - Systems factorial technology (SFT) comprises a set of powerful nonparametric
      models and measures, together with a theory-driven experiment methodology termed
      the double factorial paradigm (DFP), for assessing the cognitive information
      processing mechanisms supporting the processing of multiple sources of
      information in a given task (Townsend and Nozawa, Journal of Mathematical
      Psychology 39:321-360, 1995). We provide an overview of the model-based measures
      of SFT, together with a tutorial on designing a DFP experiment to take advantage
      of all SFT measures in a single experiment. Illustrative examples are given to
      highlight the breadth of applicability of these techniques across psychology. We
      further introduce and demonstrate a new package for performing SFT analyses using
      R for statistical computing. 

PMID- 24019065
TI  - Urological cancer: alpha-emitting radium-223-additional choices, more unknowns.

PMID- 24019064
TI  - The role of adiponectin signaling in metabolic syndrome and cancer.
AB  - The increased prevalence of obesity has mandated extensive research focused on
      mechanisms responsible for associated clinical complications. Emerging from the
      focus on adipose tissue biology as a vitally important adipokine is adiponectin
      which is now believed to mediate anti-diabetic, anti-atherosclerotic, anti
      inflammatory, cardioprotective and cancer modifying actions. Adiponectin mediates
      these primarily beneficial effects via direct signaling effects and via enhancing
      insulin sensitivity via crosstalk with insulin signaling pathways. Reduced
      adiponectin action is detrimental and occurs in obesity via decreased circulating
      levels of adiponectin action or development of adiponectin resistance. This
      review will focus on cellular mechanisms of adiponectin action, their crosstalk
      with insulin signaling and the resultant role of adiponectin in cardiovascular
      disease, diabetes and cancer and reviews data from in vitro cell based studies
      through animal models to clinical observations. 

PMID- 24019066
TI  - Chemical fingerprint analysis and quantitative determination of steroidal
      compounds from Dioscorea villosa, Dioscorea species and dietary supplements using
      UHPLC-ELSD.
AB  - Ultra high-performance liquid chromatography (UHPLC) with evaporative light
      scattering detection was used for the quantification of steroidal saponins and
      diosgenin from the rhizomes or tubers of various Dioscorea species and dietary
      supplements that were purported to contain Dioscorea. The analysis was performed
      on an Acquity UPLCTM system with an UPLCTM BEH Shield RP18 column using a
      gradient elution with water and acetonitrile. Owing to their low UV absorption,
      the steroidal saponins were observed by evaporative light scattering detection.
      The 12 compounds could be separated within 15 min using the developed UHPLC
      method with detection limits of 5-12 ug/mL with 2 MUL injection volume. The
      analytical method was validated for linearity, repeatability, accuracy, limits of
      detection and limits of quantification. The relative standard deviations for
      intra- and inter-day experiments were <3.1%, and the recovery efficiency was 97
      101%. The total content of standard compounds was found to be in the ranges 0.01
      14.5% and 0.9-28.6 mg daily intake for dry plant materials and solid commercial
      preparations, respectively. UHPLC-mass spectrometry with a quadrupole mass
      analyzer and ESI source was used only for confirmation of the identity of the
      various saponins. The developed method is simple, rapid and especially suitable
      for quality control analysis of commercial products.

PMID- 24019067
TI  - EMILIN1/alpha9beta1 integrin interaction is crucial in lymphatic valve formation
      and maintenance.
AB  - Lymphatic vasculature plays a crucial role in the maintenance of tissue
      interstitial fluid balance. The role of functional collecting lymphatic vessels
      in lymph transport has been recently highlighted in pathologies leading to
      lymphedema, for which treatments are currently unavailable. Intraluminal valves
      are of paramount importance in this process. However, valve formation and
      maturation have not been entirely elucidated yet, in particular, the role played
      by the extracellular matrix (ECM). We hypothesized that EMILIN1, an ECM
      multidomain glycoprotein, regulates lymphatic valve formation and maintenance.
      Using a mouse knockout model, we show that in the absence of EMILIN1, mice
      exhibit defects in lymphatic valve structure and in lymph flow. By applying
      morphometric in vitro and in vivo functional assays, we conclude that this
      impaired phenotype depends on the lack of alpha9beta1 integrin engagement, the
      specific lymphatic endothelial cell receptor for EMILIN1, and the ensuing
      derangement of cell proliferation and migration. Our data demonstrate a
      fundamental role for EMILIN1-integrin alpha9 interaction in lymphatic
      vasculature, especially in lymphatic valve formation and maintenance, and
      underline the importance of this ECM component in displaying a regulatory
      function in proliferation and acting as a "guiding" molecule in migration of
      lymphatic endothelial cells. 

PMID- 24019068
TI  - Drosophila oocyte polarity and cytoskeleton organization require regulation of
      Ik2 activity by Spn-F and Javelin-like.
AB  - The Drosophila melanogaster Spn-F, Ik2, and Javelin-like (Jvl) proteins interact
      to regulate oocyte mRNA localization and cytoskeleton organization. However, the
      mechanism by which these proteins interact remains unclear. Using antibodies to
      activated Ik2, we showed that this protein is found at the region of oocyte and
      follicle cell where microtubule minus ends are enriched. We demonstrate that germ
      line Ik2 activation is diminished both in jvl and in spn-F mutant ovaries.
      Structure-function analysis of Spn-F revealed that the C-terminal end is critical
      for protein function, since it alone was able to rescue spn-F sterility. On the
      other hand, germ line expression of Spn-F lacking its conserved C-terminal region
      (Spn-FDeltaC) phenocopied ik2, leading to production of ventralized eggshell and
      bicaudal embryos. In Spn-FDeltaC-expressing oocytes, Gurken protein is
      mislocalized and oskar mRNA and protein localization is disrupted. Expression of
      Ik2 rescued Spn-FDeltaC ovarian phenotypes. We found that whereas Spn-F
      physically interacts with Ik2 and Jvl, Spn-FDeltaC physically interacts with Ik2
      but not with Jvl. Thus, expression of Spn-FDeltaC, which lacks the Jvl
      interacting domain, probably interferes with interaction of Ik2 and Jvl. In
      summary, our results demonstrate that Spn-F mediates the interaction between Ik2
      and Jvl to control Ik2 activity. 

PMID- 24019069
TI  - The FBXO4 tumor suppressor functions as a barrier to BRAFV600E-dependent
      metastatic melanoma.
AB  - Cyclin D1-cyclin-dependent kinase 4/6 (CDK4/6) dysregulation is a major
      contributor to melanomagenesis. Clinical evidence has revealed that p16(INK4A),
      an allosteric inhibitor of CDK4/6, is inactivated in over half of human
      melanomas, and numerous animal models have demonstrated that p16(INK4A) deletion
      promotes melanoma. FBXO4, a specificity factor for the E3 ligase that directs
      timely cyclin D1 proteolysis, has not been studied in melanoma. We demonstrate
      that Fbxo4 deficiency induces Braf-driven melanoma and that this phenotype
      depends on cyclin D1 accumulation in mice, underscoring the importance of this
      ubiquitin ligase in tumor suppression. Furthermore, we have identified a
      substrate-binding mutation, FBXO4 I377M, that selectively disrupts cyclin D1
      degradation while preserving proteolysis of the other known FBXO4 substrate,
      TRF1. The I377M mutation and Fbxo4 deficiency result in nuclear accumulation of
      cyclin D1, a key transforming neoplastic event. Collectively, these data provide
      evidence that FBXO4 dysfunction, as a mechanism for cyclin D1 overexpression, is
      a contributor to human malignancy. 

PMID- 24019070
TI  - Glypican 1 stimulates S phase entry and DNA replication in human glioma cells and
      normal astrocytes.
AB  - Malignant gliomas are highly lethal neoplasms with limited treatment options. We
      previously found that the heparan sulfate proteoglycan glypican 1 (GPC1) is
      universally and highly expressed in human gliomas. In this study, we investigated
      the biological activity of GPC1 expression in both human glioma cells and normal
      astrocytes in vitro. Expression of GPC1 inactivates the G1/S checkpoint and
      strongly stimulates DNA replication. Constitutive expression of GPC1 causes DNA
      rereplication and DNA damage, suggesting a mutagenic activity for GPC1. GPC1
      expression leads to a significant downregulation of the tumor suppressors pRb,
      Cip/Kip cyclin-dependent kinase inhibitors (CKIs), and CDH1, and upregulation of
      the pro-oncogenic proteins cyclin E, cyclin-dependent kinase 2 (CDK2), Skp2, and
      Cdt1. These GPC1-induced changes are accompanied by a significant reduction in
      all types of D cyclins, which is independent of serum supplementation. It is
      likely that GPC1 stimulates the so-called Skp2 autoinduction loop, independent of
      cyclin D-CDK4/6. Knockdown of Skp2, CDK2, or cyclin E, three key elements within
      the network modulated by GPC1, results in a reduction of the S phase and
      aneuploid fractions, implying a functional role for these regulators in GPC1
      induced S phase entry and DNA rereplication. In addition, a significant
      activation of both the extracellular signal-regulated kinase (ERK)/mitogen
      activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt
      signaling pathways by GPC1 is seen in normal human astrocytes even in the
      presence of growth factor supplement. Both pathways are constitutively activated
      in human gliomas. The surprising magnitude and the mitogenic and mutagenic nature
      of the effect exerted by GPC1 on the cell cycle imply that GPC1 may play an
      important role in both glioma tumorigenesis and growth. 

PMID- 24019071
TI  - Noncanonical NOTCH signaling limits self-renewal of human epithelial and induced
      pluripotent stem cells through ROCK activation.
AB  - NOTCH plays essential roles in cell fate specification during embryonic
      development and in adult tissue maintenance. In keratinocytes, it is a key
      inducer of differentiation. ROCK, an effector of the small GTPase Rho, is also
      implicated in keratinocyte differentiation, and its inhibition efficiently
      potentiates immortalization of human keratinocytes and greatly improves survival
      of dissociated human pluripotent stem cells. However, the molecular basis for
      ROCK activation is not fully established in these contexts. Here we provide
      evidence that intracellular forms of NOTCH1 trigger the immediate activation of
      ROCK1 independent of its transcriptional activity, promoting differentiation and
      resulting in decreased clonogenicity of normal human keratinocytes. Knockdown of
      NOTCH1 abrogated ROCK1 activation and conferred sustained clonogenicity upon
      differentiation stimuli. Treatment with a ROCK inhibitor, Y-27632, or ROCK1
      silencing substantially rescued the growth defect induced by activated NOTCH1.
      Furthermore, we revealed that impaired self-renewal of human induced pluripotent
      stem cells upon dissociation is, at least in part, attributable to NOTCH
      dependent ROCK activation. Thus, the present study unveils a novel NOTCH-ROCK
      pathway critical for cellular differentiation and loss of self-renewal capacity
      in a subset of immature cells. 

PMID- 24019072
TI  - Major histocompatibility complex class I core promoter elements are not essential
      for transcription in vivo.
AB  - The role of core promoter elements in regulating transcription initiation is
      largely unknown for genes subject to complex regulation. Major histocompatibility
      complex class I genes are ubiquitously expressed and governed by tissue-specific
      and hormonal signals. Transcription initiates at multiple sites within the core
      promoter, which contains elements homologous to the canonical elements CCAAT,
      TATAA, Sp1 binding site (Sp1BS), and Initiator (Inr). To determine their
      functions, expression of class I transgenes with individually mutated elements
      was assessed. Surprisingly, all mutant promoters supported transcription.
      However, each mutated core promoter element had a distinct effect on expression:
      CAAT box mutations modulated constitutive expression in nonlymphoid tissues,
      whereas TATAA-like element mutations dysregulated transcription in lymphoid
      tissues. Inr mutations aberrantly elevated expression. Sp1BS element mutations
      resulted in variegated transgene expression. RNA polymerase II binding and
      histone H3K4me3 patterns correlated with transgene expression; H3K9me3 marks
      partially correlated. Whereas the wild-type, TATAA-like, and CAAT mutant
      promoters were activated by gamma interferon, the Sp1 and Inr mutants were
      repressed, implicating these elements in regulation of hormonal responses. These
      results lead to the surprising conclusion that no single element is required for
      promoter activity. Rather, each plays a distinct role in promoter activity,
      chromatin structure, tissue-specific expression, and extracellular signaling. 

PMID- 24019073
TI  - Witnesses' blindness for their own facial recognition decisions: a field study.
AB  - In a field study, we examined choice blindness for eyewitnesses' facial
      recognition decisions. Seventy-one pedestrians were engaged in a conversation by
      two experimenters who pretended to be tourists in the center of a European city.
      After a short interval, pedestrians were asked to identify the two experimenters
      from separate simultaneous six-person photo lineups. Following each of the two
      forced-choice recognition decisions, they were confronted with their selection
      and asked to motivate their decision. However, for one of the recognition
      decisions, the chosen lineup member was exchanged with a previously unidentified
      member. Blindness for this identity manipulation occurred at the rate of 40.8%.
      Furthermore, the detection rate varied as a function of similarity (high vs. low)
      between the original choice and the manipulated outcome. Finally, choice
      manipulations undermined the confidence-accuracy relation for detectors to a
      greater degree than for blind participants. Stimulus ambiguity is discussed as a
      moderator of choice blindness.

PMID- 24019074
TI  - Healthy Habits, Happy Homes: randomized trial to improve household routines for
      obesity prevention among preschool-aged children.
AB  - IMPORTANCE: Racial/ethnic and socioeconomic disparities exist across risk factors
      for childhood obesity. OBJECTIVE: To examine the effectiveness of a home-based
      intervention to improve household routines known to be associated with childhood
      obesity among a sample of low-income, racial/ethnic minority families with young
      children. DESIGN: Randomized trial. SETTING: The intervention was delivered in
      the families' homes. PARTICIPANTS: The study involved 121 families with children
      aged 2 to 5 years who had a television (TV) in the room where he or she slept;
      111 (92%) had 6-month outcome data (55 intervention and 56 control). The mean
      (SD) age of the children was 4.0 (1.1) years; 45% were overweight/obese. Fifty
      two percent of the children were Hispanic, 34% were black, and 14% were
      white/other. Nearly 60% of the families had household incomes of $20,000 or less.
      INTERVENTIONS: The 6-month intervention promoted 4 household routines, family
      meals, adequate sleep, limiting TV time, and removing the TV from the child's
      bedroom, using (1) motivational coaching at home and by phone, (2) mailed
      educational materials, and (3) text messages. Control subjects were mailed
      materials focused on child development. MAIN OUTCOMES AND MEASURES: Change in
      parent report of frequency of family meals (times/wk), child sleep duration
      (hours/d), child weekday and weekend day TV viewing (hours/d), and the presence
      of a TV in the room where the child slept from baseline to 6 months. A secondary
      outcome was change in age- and sex-adjusted body mass index (calculated as weight
      in kilograms divided by height in meters squared). RESULTS: Compared with control
      subjects, intervention participants had increased sleep duration (0.75 hours/d;
      95% CI, 0.06 to 1.44; P = .03), greater decreases in TV viewing on weekend days (
      1.06 hours/d; 95% CI, -1.97 to -0.15; P = .02), and decreased body mass index (
      0.40; 95% CI, -0.79 to 0.00; P = .05). No significant intervention effect was
      found for the presence of a TV in the room where the child slept or family meal
      frequency. CONCLUSIONS AND RELEVANCE: Our results suggest that promoting
      household routines, particularly increasing sleep duration and reducing TV
      viewing, may be an effective approach to reduce body mass index among low-income,
      racial/ethnic minority children. Longer-term studies are needed to determine
      maintenance of behavior change. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT01565161.

PMID- 24019075
TI  - Expanding the library and substrate diversity of the pyrrolysyl-tRNA synthetase
      to incorporate unnatural amino acids containing conjugated rings.
AB  - Unnatural amino acids (UAAs) containing conjugated ring systems are of interest
      for their optical properties. Until now, such bulky and planar UAAs could not be
      incorporated into proteins using the pyrrolysyl tRNA/synthetase shuttling system.
      Using the "small-intelligent" approach to construct a highly diverse library, we
      evolved novel synthetases specific for two such UAAs and incorporated them into
      proteins in E. coli and mammalian cells. 

PMID- 24019076
TI  - A chemical genomics approach to identification of interactions between bioactive
      molecules and alternative reading frame proteins.
AB  - Magic Tag(r) immobilisation of bioactive molecules coupled with bacteriophage
      display, followed by an ELISA assay, provides a protocol that can probe
      interactions of drugs with putative products of alternative initiation of
      translation as exemplified by the binding of immobilised flecainide to protein
      products of genes linked to sudden cardiac death. 

PMID- 24019077
TI  - De novo malignant disease after liver transplantation? Risk and surveillance
      strategies.

PMID- 24019078
TI  - An unprecedented (3,4,24)-connected heteropolyoxozincate organic framework as
      heterogeneous crystalline Lewis acid catalyst for biodiesel production.
AB  - A novel 3D hexadecanuclear heteropolyoxozincate organic framework, IFMC-200, has
      been successfully synthesized based on a late transition metal-oxygen cluster.
      IFMC-200 not only represents the first example of (3,4,24)-connected framework
      but also contains the first 24-connected single metal cluster in a crystal
      structure. It exhibits superior thermal stability, good water-stability, and even
      insensitivity to the existence of acid and base within a certain range of pH
      values. Furthermore, it performs as a heterogeneous crystalline Lewis acid
      catalyst with good activity for the conversion of long-chain fatty acids rather
      than short-chain ones, and high recycling efficiency for esterification reaction
      of fatty acids with alcohols to produce biodiesel. 

PMID- 24019079
TI  - Study of intrathyroid fat-containing lesions using CT imaging with literature
      review.
AB  - INTRODUCTION: This study was conducted to estimate the incidence of intrathyroid
      fat-containing lesions based in the general population on CT imaging. The imaging
      characteristics of the lesions on CT were also analyzed. METHODS: This
      retrospective study included data for 1,205 patients who underwent neck CT at our
      institution from January 2012 to January 2013. Data concerning size, shape,
      homogeneity of attenuation and location of lesions, and the presence of a fatty
      band connecting to extrathyroid fat were evaluated. Pathologic specimens were
      reevaluated when available. A literature review was conducted based on 16 peer
      reviewed articles describing intrathyroid fat-containing lesions. RESULTS:
      Intrathyroid fat-containing lesions were detected in 13 patients (1.2 %). The
      mean lesion size was 5.7 mm (range, 2.6-10.6 mm). Nodular shape (92 %),
      homogeneous attenuation (92 %), and the fatty band (77 %) were common CT
      features. Posterior (85 %), medial (85 %), and upper (92 %) aspects of the
      thyroid gland were most commonly involved. In four patients who underwent
      surgery, one had fat-containing nodular hyperplasia, one had ectopic thymic
      tissue within mature fat, and one had mature fat itself. In 16 previously
      reported studies, the 41 lesions presented two fat infiltration patterns, diffuse
      (n = 12) and localized (n = 29), and two lesions showed mature fat tissue itself.
      CONCLUSION: Intrathyroidal fat-containing lesions were found in 1.2 % of patients
      presenting for neck CT. Almost all of the lesions occurred in common locations
      and showed similar features on CT, including nodular shape, homogeneous
      attenuation, and a fatty band.

PMID- 24019080
TI  - Adalimumab is more effective than azathioprine and mesalamine at preventing
      postoperative recurrence of Crohn's disease: a randomized controlled trial.
AB  - OBJECTIVES: Postsurgical recurrence of Crohn's disease (CD) is very frequent and,
      to date, only infliximab has been shown to be useful in preventing it. The
      efficacy of adalimumab (ADA) is poorly known. We evaluated whether the
      administration of ADA after resective intestinal surgery reduces postoperative CD
      recurrence. METHODS: We randomly assigned 51 patients with CD who had undergone
      ileocolonic resection to receive after 2 weeks from surgery ADA at the dose of
      160/80/40 mg every two weeks, azathioprine (AZA) at 2 mg/kg/day, or mesalamine at
      3 g/day, and they were followed up for 2 years. The primary end point was the
      proportion of patients with endoscopic and clinical recurrence. Secondary end
      point was the assessment of quality of life by means of a previously validated
      questionnaire. RESULTS: The rate of endoscopic recurrence was significantly lower
      in ADA (6.3%) compared with the AZA (64.7%; odds ratio (OR)=0.036 (95% confidence
      interval (CI) 0.004-0.347)) and mesalamine groups (83.3%; OR=0.013 (95% CI 0.001
      0.143)). There was a significantly lower proportion of patients in clinical
      recurrence in the ADA group (12.5%) compared with the AZA (64.7%; OR=0.078 (95%
      CI 0.013-0.464)) and mesalamine groups (50%; (OR=0.143 (95% CI 0.025-0.819)). The
      quality of life was higher in the ADA (202) than in the AZA (90; OR=0.028 (95% CI
      0.004-0.196)) and mesalamine groups (98; OR=0.015 (95% CI 0.002-0.134)).
      CONCLUSIONS: The administration of ADA after intestinal resective surgery was
      greatly effective in preventing endoscopic and clinical recurrence of CD. Further
      larger studies are necessary to confirm the therapeutic advantage and to show the
      economic implications of biologic therapy in this field.

PMID- 24019082
TI  - The influence of pore size and surface area of activated carbons on the
      performance of ionic liquid based supercapacitors.
AB  - This study analyses and compares the behaviour of 5 commercial porous carbons in
      the ionic liquid N-butyl-N-methylpyrrolidinium bis(trifluoromethanesulfonyl)imide
      (PYR14TFSI) and its mixture with propylene carbonate (PC) as electrolytes. The
      results of this investigation show that the existence of a distribution of pore
      sizes and/or constrictions at the entrance of the pores leads to significant
      changes in the specific capacitance of the investigated materials. The use of
      PYR14TFSI as an electrolyte has a positive effect on the EDLC energy storage, but
      its high viscosity limits the power density. The mixture 50 : 50 wt% propylene
      carbonate-PYR14TFSI provides high operative voltage as well as low viscosity and
      thus notably enhances EDLC operation. 

PMID- 24019081
TI  - Multiple rapid swallow responses during esophageal high-resolution manometry
      reflect esophageal body peristaltic reserve.
AB  - OBJECTIVES: Dysphagia may develop following antireflux surgery as a consequence
      of poor esophageal peristaltic reserve. We hypothesized that suboptimal
      contraction response following multiple rapid swallows (MRS) could be associated
      with chronic transit symptoms following antireflux surgery. METHODS: Wet swallow
      and MRS responses on esophageal high-resolution manometry (HRM) were
      characterized collectively in the esophageal body (distal contractile integral
      (DCI)), and individually in each smooth muscle contraction segment (S2 and S3
      amplitudes) in 63 patients undergoing antireflux surgery and in 18 healthy
      controls. Dysphagia was assessed using symptom questionnaires. The MRS/wet
      swallow ratios were calculated for S2 and S3 peak amplitudes and DCI. MRS
      responses were compared in patients with and without late postoperative dysphagia
      following antireflux surgery. RESULTS: Augmentation of smooth muscle contraction
      (MRS/wet swallow ratios >1.0) as measured collectively by DCI was seen in only
      11.1% with late postoperative dysphagia, compared with 63.6% in those with no
      dysphagia and 78.1% in controls (P<=0.02 for each comparison). Similar results
      were seen with S3 but not S2 peak amplitude ratios. Receiver operating
      characteristics identified a DCI MRS/wet swallow ratio threshold of 0.85 in
      segregating patients with late postoperative dysphagia from those with no
      postoperative dysphagia with a sensitivity of 0.67 and specificity of 0.64.
      CONCLUSIONS: Lack of augmentation of smooth muscle contraction following MRS is
      associated with late postoperative dysphagia following antireflux surgery,
      suggesting that MRS responses could assess esophageal smooth muscle peristaltic
      reserve. Further research is warranted to determine if antireflux surgery needs
      to be tailored to the MRS response.

PMID- 24019083
TI  - Low levels of high-density lipoprotein cholesterol predict the presence of
      coronary artery disease in patients with aortic aneurysms.
AB  - To identify predictors of the presence of coronary artery disease (CAD) in
      patients with planned surgery for aortic aneurysms, we reviewed clinical profiles
      and angiography records of 191 patients with aortic aneurysms (34 thoracic, 137
      abdominal, and 20 thoracoabdominal; 162 men; mean age, 75.2 +/- 7.7 years). The
      incidence of CAD was 38.7% among all the patients. Patients with CAD had
      significantly low levels of high-density lipoprotein cholesterol (HDL-C) as
      compared with patients without CAD (45 +/- 9 vs 51 +/- 13 mg/dL; P = .009).
      Multivariate analysis showed that only low HDL-C levels were associated with the
      presence of CAD (adjusted odds ratio, 0.946; 95% confidence interval, 0.911
      0.983; P = .004). The optimal cutoff level of HDL-C to predict CAD was 47.50
      mg/dL. The CAD is common in patients with aortic aneurysms, and low levels of HDL
      C are independently associated with the presence of CAD. 

PMID- 24019084
TI  - Endothelial and platelet function in children with previous Kawasaki disease.
AB  - We investigated whether children with a previous Kawasaki disease (KD) have
      evidence of abnormal vascular and/or platelet function. We included 14 patients
      with previous KD and 14 matched controls. We assessed endothelial function by
      flow-mediated dilation (FMD), carotid intima-media thickness (cIMT), coronary
      microvascular function by coronary blood flow response (CBFR) to cold pressor
      test, and platelet reactivity by measuring monocyte-platelet aggregates (MPAs)
      and CD41-platelet expression by flow cytometry. No differences were found between
      the groups in FMD, cIMT, or CBFR to cold pressor test. The MPAs were similar in
      patients with KD and controls. CD41-platelet expression, however, was
      significantly increased in patients with KD compared with controls, both at rest
      (14.3 +/- 1.9 vs 12.4 +/- 1.9 mean fluorescence intensity [mfi], P = .01) and
      after adenosine diphosphate stimulation (19.3 +/- 1.3 vs 17 +/- 1.7 mfi, P <
      .001). In conclusion, children with a previous episode of KD showed increased
      platelet activation, compared with healthy participants despite no apparent
      vascular abnormality at follow-up. 

PMID- 24019085
TI  - Can statins alter coronary plaque morphology assessed by intravascular
      ultrasound?

PMID- 24019086
TI  - Neutrophil-lymphocyte ratio and C-reactive protein may be correlated in patients
      with coronary artery ectasia.

PMID- 24019087
TI  - Is increased mean platelet volume an indicator of subclinical atherosclerosis in
      patients with Behcet disease?

PMID- 24019088
TI  - Use of emergency medical services in the second gulf registry of acute coronary
      events.
AB  - Data are scarce regarding emergency medical service (EMS) usage by patients with
      acute coronary syndrome (ACS) in the Arabian Gulf region. This 9-month in
      hospital prospective ACS registry was conducted in Arabian Gulf countries, with
      30-day and 1-year follow-up mortality rates. Of 5184 patients with ACS, 1293
      (25%) arrived at the hospital by EMS. The EMS group (vs non-EMS) was more likely
      to be male, have cardiac arrest on presentation, be current or exsmokers, and
      have moderate or severe left ventricular dysfunction and ST-segment elevation
      myocardial infarction (STEMI). The EMS group had higher crude mortality rates
      during hospitalization and after hospital discharge but not after adjustment for
      clinical factors and treatments. The EMSs are underused in the Arabian Gulf
      region. Short- and long-term mortality rates in patients with ACS are similar
      between those who used and did not use EMS. Quality improvement in the EMS
      infrastructure and establishment of integrated STEMI networks are urgently
      needed. 

PMID- 24019091
TI  - Heterodinuclear lanthanoid-containing polyoxometalates: stepwise synthesis and
      single-molecule magnet behavior.
AB  - Polyoxometalates (POMs) with heterodinuclear lanthanoid cores, TBA8H4[{Ln(MU2
      OH)2Ln'}(gamma-SiW10O36)2] (LnLn'; Ln = Gd, Dy; Ln' = Eu, Yb, Lu; TBA = tetra-n
      butylammonium), were successfully synthesized through the stepwise incorporation
      of two types of lanthanoid cations into the vacant sites of lacunary [gamma
      SiW10O36](8-) units without the use of templating cations. The incorporation of a
      Ln(3+) ion into the vacant site between two [gamma-SiW10O36](8-) units afforded
      mononuclear Ln(3+)-containing sandwich-type POMs with vacant sites (Ln1;
      TBA8H5[{Ln(H2O)4}(gamma-SiW10O36)2]; Ln = Dy, Gd, La). The vacant sites in Ln1
      were surrounded by coordinating W-O and Ln-O oxygen atoms. On the addition of one
      equivalent of [Ln'(acac)3] to solutions of Dy1 or Gd1 in 1,2-dichloroethane
      (DCE), heterodinuclear lanthanoid cores with bis(MU2-OH) bridging ligands,
      [Dy(MU2-OH)2Ln'](4+), were selectively synthesized (LnLn'; Ln = Dy, Gd; Ln' = Eu,
      Yb, Lu). On the other hand, La1, which contained the largest lanthanoid cation,
      could not accommodate a second Ln'(3+) ion. DyLn' showed single-molecule magnet
      behavior and their energy barriers for magnetization reversal (DeltaE/kB) could
      be manipulated by adjusting the coordination geometry and anisotropy of the
      Dy(3+) ion by tuning the adjacent Ln'(3+) ion in the heterodinuclear [Dy(MU2
      OH)2Ln'](4+) cores. The energy barriers increased in the order: DyLu (DeltaE/kB =
      48 K) < DyYb (53 K) < DyDy (66 K) < DyEu (73 K), with an increase in the ionic
      radii of Ln'(3+); DyEu showed the highest energy barrier.

PMID- 24019090
TI  - Role of mitogen-activated protein kinases and Mcl-1 in apoptosis induction by
      withaferin A in human breast cancer cells.
AB  - Withaferin A (WA), a bioactive constituent of Ayurvedic medicine plant Withania
      somnifera, is a potent apoptosis inducer in cancer cells but the mechanism of
      cell death induction is not fully characterized. The present study was undertaken
      to determine the role of mitogen-activated protein kinases (MAPK), including c
      jun NH2 -terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and
      p38 MAPK, and anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) in
      regulation of WA-induced apoptosis using human breast cancer cells. Exposure of
      MCF-7 (estrogen responsive) and SUM159 (triple negative) human breast cancer
      cells to WA resulted in increased phosphorylation of ERK, JNK, and p38 MAPK, but
      these effects were relatively more pronounced in the former cell line than in
      SUM159. Overexpression of manganese-superoxide dismutase conferred partial
      protection against WA-mediated hyperphosphorylation of ERK, but not JNK or p38
      MAPK. Cell death resulting from WA treatment in MCF-7 cells was significantly
      augmented by pharmacological inhibition of ERK and p38 MAPK. Interestingly, the
      WA-induced apoptosis in MCF-7 cells was partially but significantly blocked in
      the presence of a JNK-specific inhibitor. Pharmacological inhibition of ERK or
      JNK had no effect on WA-induced apoptosis in SUM159 cells. The WA-treated cells
      exhibited induction of long and short forms of Mcl-1. RNA interference of Mcl-1
      alone triggered apoptosis. Furthermore, the WA-induced cell death in MCF-7 cells
      was modestly but significantly augmented by knockdown of the Mcl-1 protein. These
      observations indicate that: MAPK have cell line-specific role in cell death by
      WA, and Mcl-1 induction confers modest protection against WA-induced apoptosis.

PMID- 24019092
TI  - Comparison of PET imaging with 64Cu-liposomes and 18F-FDG in the 7,12
      dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch model of oral
      dysplasia and squamous cell carcinoma.
AB  - PURPOSE: Currently, 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) is the gold
      standard radiotracer for staging of head and neck cancer; however, the low
      sensitivity of this tracer can impede detection of early lesions. (64)Cu
      liposomes accumulate in various cancers and provide both a sensitive tracer and
      an indication of the biodistribution of nanotherapeutics. Here, the accumulation
      of (64)Cu-liposomes in early and established cancers is assessed and compared
      with (18)F-FDG in a head and neck cancer model. METHODS: Lesions ranging from
      mild dysplasia to squamous cell carcinoma were induced in a hamster model of head
      and neck cancer by topical application of 7,12-dimethylbenz[a]anthracene to the
      buccal pouch. The hamsters were imaged with micro-positron emission tomography
      using (18)F-FDG and (64)Cu-liposomes. RESULTS: At 24 h postinjection, (64)Cu
      liposome accumulation exceeded the accumulation of (18)F-FDG in every pathologic
      grade. The lesion-to-cheek pouch (background) ratio and lesion-to-brain ratio
      were also higher for (64)Cu-liposomes than for (18)F-FDG. CONCLUSION: Imaging of
      a nanotracer such as (64)Cu-liposomes can improve the visualization of head and
      neck tumors. Accumulation of liposomal particles in head and neck tumors over
      various pathologic grades averaged 3.5%ID/cc demonstrating the potential for
      liposomal therapy with targeted chemotherapeutic agents.

PMID- 24019093
TI  - A case report of nocardiosis at the cauda equina.

PMID- 24019094
TI  - Solitary fibrous tumor in the pelvis: induced hypoglycemia associated with
      insulin-like growth factor II.

PMID- 24019096
TI  - Functional genetics in the post-genomics era: building a better roadmap in
      Drosophila.
AB  - In this commentary, Rob Kulathinal describes two papers from the Perrimon
      laboratory, each describing a new online resource that can assist geneticists
      with the design of their RNAi experiments. Hu et al.'s "UP-TORR: online tool for
      accurate and up-to-date annotation of RNAi reagents" and "FlyPrimerBank: An
      online database for Drosophila melanogaster gene expression analysis and
      knockdown evaluation of RNAi reagents" are published, respectively, in this
      month's issue of GENETICS and G3: Genes|Genomes|Genetics. 

PMID- 24019095
TI  - Mid-term results of computer-assisted cervical reconstruction for rheumatoid
      cervical spines.
AB  - STUDY DESIGN: A retrospective single-center study. We routinely have used C1-C2
      transarticular and cervical pedicle screw fixations to reconstruct highly
      destructed unstable rheumatoid arthritis (RA) cervical lesions. However, there is
      little data on mid-term results of surgical reconstruction for rheumatoid
      cervical disorders, particularly, cervical pedicle screw fixation. OBJECTIVES:
      The purpose of this study was to evaluate the mid-term surgical results of
      computer-assisted cervical reconstruction for such lesions. METHODS: Seventeen
      subjects (4 men, 13 women; mean age, 61 +/- 9 years) with RA cervical lesions who
      underwent C1-C2 transarticular screw fixation or occipitocervical fixation, with
      at least 5 years follow-up were studied. A frameless, stereotactic,
      optoelectronic, CT-based image-guidance system, was used for correct screw
      placement. Variables including the Japanese Orthopaedic Association (JOA) score,
      Ranawat class, EuroQol (EQ-5D), atlantodental interval, and Ranawat values
      before, and at 2 and 5 years after surgery, were evaluated. Furthermore, screw
      perforation rates were evaluated. RESULTS: The lesions included atlantoaxial
      subluxation (AAS, n = 6), AAS + vertical subluxation (VS, n = 7), and AAS + VS +
      subaxial subluxation (n = 4). There was significant neurological improvement at 2
      years after surgery, as evidenced by the JOA scores, Ranawat class, and the EQ-5D
      utility weight. However, at 5 years after surgery, there was a deterioration of
      this improvement. The Ranawat values before, and at 2 and 5 years after surgery,
      were not significantly different. Major screw perforation rate was 2.1 %. No
      neural and vascular complications associated with screw insertion were observed.
      CONCLUSIONS: Subjects with rheumatoid cervical lesions who underwent C1-C2
      transarticular screw fixation or occipitocervical fixation using a pedicle screw
      had significantly improved clinical parameters at 2 years after surgery. However,
      there was a deterioration of this improvement at 5 years post surgery.

PMID- 24019098
TI  - Effects of orally administered yeast-derived beta-glucans: a review.
AB  - Yeast-derived beta-glucans (Y-BG) are considered immunomodulatory compounds
      suggested to enhance the defense against infections and exert anticarcinogenic
      effects. Specific preparations have received Generally Recognized as Safe status
      and acceptance as novel food ingredients by European Food Safety Authority. In
      human trials, orally administered Y-BG significantly reduced the incidence of
      upper respiratory tract infections in individuals susceptible to upper
      respiratory tract infections, whereas significant differences were not seen in
      healthy individuals. Increased salivary IgA in healthy individuals, increased IL
      10 levels in obese subjects, beneficial changes in immunological parameters in
      allergic patients, and activated monocytes in cancer patients have been reported
      following Y-BG intake. The studies were conducted with different doses (7.5-1500
      mg/day), using different preparations that vary in their primary structure,
      molecular weight, and solubility. In animal models, oral Y-BG have reduced the
      incidence of bacterial infections and levels of stress-induced cytokines and
      enhanced antineoplastic effects of cytotoxic agents. Protective effects toward
      drug intoxication and ischemia/reperfusion injury have also been reported. In
      conclusion, additional studies following good clinical practice principles are
      needed in which well-defined Y-BG preparations are used and immune markers and
      disease endpoints are assessed. Since optimal dosing may depend on preparation
      characteristics, dose-response curves might be assessed to find the optimal dose
      for a specific preparation. 

PMID- 24019099
TI  - The impact of family transitions on child fostering in rural Malawi.
AB  - Despite the frequency of divorce and remarriage across much of sub-Saharan
      Africa, little is known about what these events mean for the living arrangements
      of children. We use longitudinal data from rural Malawi to examine the effects of
      family transitions on the prevalence and incidence of child fostering, or
      children residing apart from their living parents. We find that between 7 % and
      15 % of children aged 3-14 are out-fostered over the two-year intersurvey period.
      Although divorce appears to be a significant driver of child fostering in the
      cross-sectional analysis, it is not significantly associated with the incidence
      of out-fostering. In contrast, maternal remarriage has both a lagged and an
      immediate effect on the incidence of out-fostering. Furthermore, the likelihood
      of out-fostering is even higher among children whose mother remarried and had a
      new child during the intersurvey period. Using longitudinal data collected from
      living mothers rather than from children's current foster homes offers new
      insights into the reasons children are sent to live with others besides their
      parents. 

PMID- 24019100
TI  - Genetic bio-ancestry and social construction of racial classification in social
      surveys in the contemporary United States.
AB  - Self-reported race is generally considered the basis for racial classification in
      social surveys, including the U.S. census. Drawing on recent advances in human
      molecular genetics and social science perspectives of socially constructed race,
      our study takes into account both genetic bio-ancestry and social context in
      understanding racial classification. This article accomplishes two objectives.
      First, our research establishes geographic genetic bio-ancestry as a component of
      racial classification. Second, it shows how social forces trump biology in racial
      classification and/or how social context interacts with bio-ancestry in shaping
      racial classification. The findings were replicated in two racially and
      ethnically diverse data sets: the College Roommate Study (N = 2,065) and the
      National Longitudinal Study of Adolescent Health (N = 2,281). 

PMID- 24019101
TI  - Pathological and oncologic outcomes for men with positive lymph nodes at radical
      prostatectomy: The Johns Hopkins Hospital 30-year experience.
AB  - BACKGROUND: We report the 30-year institutional experience of radical
      prostatectomy (RP) for men with clinically localized prostate cancer (PC) found
      to have lymph node (LN) metastases at surgery. METHODS: The Johns Hopkins RP
      Database (1982-2011) was queried for 505 (2.5%) men with node-positive (N1) PC.
      Survival analysis was completed using the Kaplan-Meier method and proportional
      hazard regression models. RESULTS: The proportion of men with N1PC was 8.3%,
      3.5%, and 1.4% in the pre- (1982-1990), early- (1991-2000), and contemporary-PSA
      eras (2001-2011), respectively. A trend toward decreasing PSA, less palpable
      disease but more advanced Gleason sum was noted in the most contemporary era.
      Median total and positive nodes were 13.2 (1-41) and 1.7 (1-12), respectively. Of
      135 patients with a unilateral tumor, 80 (59.3%), 28 (20.7%), and 15 (11.1%) had
      ipsilateral, contralateral, and bilateral positive LN. 15-year biochemical
      recurrence free, metastases-free and cancer-specific survival was 7.1%, 41.5%,
      and 57.5%, respectively. Predictors of biochemical-recurrence, metastases and
      death from PC in multivariate analysis included Gleason sum at RP, the number and
      percent of positive LN; notably total number of LN dissected did not predict
      outcome. CONCLUSIONS: In this highly-selected RP cohort, men found to have N1PC
      disease at RP can experience a durable long-term metastases-free and cancer
      specific survival. Predictors of survival include Gleason sum, number, and
      percentage of positive LN. While total number of LN dissected was not predictive,
      approximately 30% of men with N1PC will have positive LN contralateral to the
      primary prostatic lesion highlighting the importance of a thorough, bilateral
      pelvic LN dissection.

PMID- 24019102
TI  - [Acute right heart failure in pulmonary hypertension].

PMID- 24019103
TI  - The continuing importance of how neonates die.

PMID- 24019104
TI  - Magnetic resonance spectroscopy in bio(in)organic chemistry and in mechanistic
      systems biology: a tribute to Ivano Bertini.

PMID- 24019105
TI  - 18-month outcomes of a community-based treatment for childhood obesity.
AB  - BACKGROUND: Few studies have evaluated community-based interventions for
      childhood obesity and even fewer provide efficacy data 1 year later. OBJECTIVES:
      This study assessed changes in relative weight 1 year after a 6-month treatment
      for childhood obesity. METHODS: Participants were 155 overweight/obese
      children/adolescents and their caregivers. The primary outcome was change in
      child percent over body mass index (BMI) from 6 to 18 months. The primary outcome
      was also assessed from 0 to 18 months and changes in secondary outcomes (BMI z
      score, guardian weight, health-related quality of life [HRQoL]) were examined
      from 6-18 to 0-18 months. RESULTS: From 6 to 18 months, there were no significant
      changes in any outcome. From 0 to 18 months, there were improvements in BMI z
      score (P < 0.001), HRQoL (P < 0.001) and guardian weight (P = 0.02). CONCLUSIONS:
      Changes in relative weight and HRQoL observed after 6 months persisted 1 year
      later. The programme produced reductions in BMI z-score and obesity prevalence
      but not in percent over BMI from 0 to 18 months.

PMID- 24019107
TI  - Hepatic artery thrombosis: conservative management or retransplantation?

PMID- 24019106
TI  - Dynamic molecular monitoring of retina inflammation by in vivo Raman spectroscopy
      coupled with multivariate analysis.
AB  - Retinal tissue is damaged during inflammation in Multiple Sclerosis. We assessed
      molecular changes in inflamed murine retinal cultures by Raman spectroscopy.
      Partial Least Squares-Discriminant analysis (PLS-DA) was able to classify retina
      cultures as inflamed with high accuracy. Using Multivariate Curve Resolution
      (MCR) analysis, we deconvolved 6 molecular components suffering dynamic changes
      along inflammatory process. Those include the increase of immune mediators
      (Lipoxygenase, iNOS and TNFalpha), changes in molecules involved in energy
      production (Cytochrome C, phenylalanine and NADH/NAD+) and decrease of
      Phosphatidylcholine. Raman spectroscopy combined with multivariate analysis
      allows monitoring the evolution of retina inflammation.

PMID- 24019108
TI  - N-acetyl-L-cysteine enhances fisetin-induced cytotoxicity via induction of ROS
      independent apoptosis in human colonic cancer cells.
AB  - Oxidative stress or excessive antioxidant levels-caused redox imbalance can alter
      apoptotic responses, and N-acetyl-L-cysteine (NAC) was able to inhibit H2 O2 
      mediated cell death, but unable to prevent apoptosis induced by other chemicals
      such as etoposide. We now demonstrate that 10 and 20 mM NAC, non-toxic
      concentrations, can enhance fisetin (FIS)-mediated apoptosis in colon cancer
      cells COLO205. Compared to treatment with FIS alone, combination treatment with
      NAC increased the expression of cleaved caspase-3 and PAPR protein, and produced
      greater density of DNA ladders. NAC reduced the mitochondrial membrane potential
      of FIS-treated COLO205 cells with induction of caspase 9 protein cleavage. DNA
      ladders induced by FIS + NAC were diminished by adding the caspase 3 inhibitor,
      DEVD-FMK, and the caspase 9 inhibitor, YVAD-FMK. Combinatorial treatment COLO205
      cells with NAC and FIS showed potent inhibition on ERK protein phosphorylation,
      compared with those from FIS or NAC-treated groups by Western blotting using
      specific antibodies. Addition of the chemical ERK inhibitors, PD98059 and U0126,
      significantly inhibited ERK protein phosphorylation, accompanied by induced DNA
      ladder formation, cleavage of caspase 3 and PARP protein in COLO205 cells.
      Furthermore, NAC showed an enhancement on a FIS-related chemical chrysin-induced
      apoptosis of COLO205 cells, and NAC sensitization of colon cancer cells to FIS
      induced apoptosis was also identify in colonic cancer cells HCT-116, HT-29, and
      HCT-15 cells. The evidence to support NAC sensitizing human colon cancer cells to
      FIS-induced apoptosis was provided, and application of NAC and FIS as a strategy
      to treat colonic cancer deserved for further in vivo study.

PMID- 24019109
TI  - Concealed cyclotrimeric polymorph of lithium 2,2,6,6-tetramethylpiperidide
      unconcealed: X-ray crystallographic and NMR spectroscopic studies.
AB  - Lithium 2,2,6,6-tetramethylpiperidide (LiTMP), one of the most important polar
      organometallic reagents both in its own right and as a key component of ate
      compositions, has long been known for its classic cyclotetrameric (LiTMP)4 solid
      state structure. Made by a new approach through transmetalation of Zn(TMP)2 with
      tBuLi in n-hexane solution, a crystalline polymorph of LiTMP has been uncovered.
      X-ray crystallographic studies at 123(2) K revealed this polymorph crystallises
      in the hexagonal space group P63 /m and exhibited a discrete cyclotrimeric (C3h )
      structure with a strictly planar (LiN)3 ring containing three symmetrically
      equivalent TMP chair-shaped ligands. The molecular structure of (LiTMP)4 was
      redetermined at 123(2) K, because its original crystallographic characterisation
      was done at ambient temperature. This improved redetermination confirmed a
      monoclinic C2/c space group with the planar (LiN)4 ring possessing pseudo (non
      crystallographic) C4h symmetry. Investigation of both metalation and
      transmetalation routes to LiTMP under different conditions established that
      polymorph formation did not depend on the route employed but rather the
      temperature of crystallisation. Low-temperature (freezer at -35  degrees C)
      cooling of the reaction solution favoured (LiTMP)3 ; whereas high-temperature
      (bench) storage favoured (LiTMP)4 . Routine (1) H and (13) C NMR spectroscopic
      studies in a variety of solvents showed that (LiTMP)3 and (LiTMP)4 exist in
      equilibrium, whereas (1) H DOSY NMR studies gave diffusion coefficient results
      consistent with their relative sizes. 

PMID- 24019110
TI  - The effects of colesevelam HCl on the single-dose pharmacokinetics of
      glimepiride, extended-release glipizide, and olmesartan medoxomil.
AB  - Bile acid sequestrants can potentially bind to concomitant drugs. Single-dose
      studies evaluated the effects of colesevelam on the pharmacokinetics of
      glimepiride, glipizide extended-release (ER), and olmesartan medoxomil. Each
      study enrolled healthy subjects aged 18-45 years. The olmesartan medoxomil study
      used a randomized adaptive crossover design that initially compared olmesartan
      medoxomil alone versus simultaneously with colesevelam, then olmesartan medoxomil
      alone versus 4 hours before colesevelam. The other studies used a three-period
      crossover design (test drug alone, test drug simultaneously with colesevelam, and
      test drug 4 hours before colesevelam). For the colesevelam coadministration
      periods, 3,750 mg once daily was dosed throughout the pharmacokinetic sampling
      period. After each single dose of test drug, serial blood samples were collected
      for determination of plasma drug concentrations and calculation of
      pharmacokinetic parameters. Administering colesevelam simultaneously with
      glimepiride or glipizide ER resulted in minor reductions (18% and 13%,
      respectively) in total exposure that were negated by staggering colesevelam
      dosing by 4 hours. Administering colesevelam simultaneously with olmesartan
      medoxomil resulted in a major reduction (39%) in olmesartan exposure that was
      reduced by staggering colesevelam dosing by 4 hours. This reduction in olmesartan
      exposure is not predicted to have a clinically significant impact on blood
      pressure control. 

PMID- 24019111
TI  - Life testing of LSM-YSZ composite electrodes under reversing-current operation.
AB  - Durability testing of solid oxide cell electrodes in reversing-current and
      constant-current operation modes is presented. (La0.8Sr0.2)0.98MnO3-delta
      Zr0.84Y0.16O2-gamma (LSM-YSZ) symmetric cells were tested at 800  degrees C in
      air with current densities of 0.5 and 1.5 A cm(-2), with current cycle periods of
      1 and 12 h. A continuous increase in both ohmic and polarization resistance was
      observed, via Electrochemical Impedance Spectroscopy (EIS), for cells tested with
      a reversing current of 1.5 A cm(-2), whereas cells tested at 0.5 A cm(-2) showed
      no measurable resistance increase. The resistance degradation was explained by
      delamination in the electrode, observed by post-test Scanning Electron Microscopy
      (SEM), near the interface with the electrolyte for the 1.5 A cm(-2) cells, but
      not for those tested at 0.5 A cm(-2). Current cycle period also impacted the
      degradation observed at 1.5 A cm(-2): both the rate of resistance increase and
      the extent of post-test delamination decreased on going from constant current
      mode to a 12 h period to a 1 h period. The results indicate that lower current
      densities and reversing-current operation are desirable to maximize the lifetime
      of solid oxide cells. 

PMID- 24019113
TI  - Obesity: Does bariatric surgery improve offspring health?

PMID- 24019114
TI  - Diabetes: Macrophages mediate beta-cell loss in T2DM.

PMID- 24019112
TI  - Osteoporosis in men.
AB  - Osteoporotic fractures in older men (>50 years of age) are common and associated
      with considerable mortality and morbidity, but osteoporosis in men is under
      recognized and undertreated. Secondary osteoporosis is also common in men, and
      causes include androgen deprivation therapy for prostate cancer, glucocorticoid
      treatment and alcohol excess. Clinical trials have demonstrated the efficacy of
      pharmacological osteoporosis treatments in men in terms of increasing BMD and
      decreasing levels of bone turnover markers; however, few trials have included
      fracture reduction end points. This Review will consider the pathophysiology of
      osteoporosis in men and the evidence for testing and treatment. The aims of the
      Review are to inform clinical practice, to discuss the current evidence base and
      to highlight the 2012 Endocrine Society clinical practice guidelines on
      osteoporosis in men. 

PMID- 24019115
TI  - Alterations in both the activatory and inhibitory potential of peripheral blood
      CD4+ T cells in rheumatoid arthritis patients correlate with disease progression.
AB  - The chronic nature of rheumatoid arthritis (RA) suggests immune dysfunction,
      including persistent systemic activation. Therefore, we evaluated the activatory
      and inhibitory potential as well as proliferative activity of peripheral blood
      (PB) CD4+ T cells from RA patients in different stages of the disease and after
      different therapeutic interventions. We found that CD4+ T cells from RA patients
      were activated in vivo concerning decreased CD28 expression and increase of
      CD40L, CD69, and CTLA-4 expression; however, the extent of stimulation was
      suboptimal when compared to healthy controls. Consequently, impaired
      proliferative activities of these cells were found in all patients irrespective
      of the active disease duration. Treatment with methotrexate (MTX) and/or
      inhibitors of TNF-alpha (iTNF) did not significantly influence systemic
      activation in RA patients, which corresponded with the maintenance of
      inflammation markers; however, partial restoration of CD28 and CTLA-4 expression
      as well as clinical improvement were observed. In patients with early disease
      (the MTX group), we noted higher capacity of CD4+ T cells for restoration of T
      cell function, whereas cells from the iTNF group with progressive disease
      remained with a proliferative defect after the treatment. In conclusion, our
      study demonstrates that the dysregulated expression of molecules interfering with
      CD4+ T cell signaling may result in functional impairment of the effector T cells
      and correlates with disease progression.

PMID- 24019116
TI  - Proximal duodenal obstruction associated with compression from a replaced right
      hepatic artery.
AB  - Replaced right hepatic artery is a well-described normal anatomical variant, not
      previously associated with acute or chronic abdominal symptoms or long-term
      sequelae. We report a 15-year-old girl presenting with nearly a decade of
      symptoms secondary to external compression of the proximal duodenum by the
      ventral passage of a replaced right hepatic artery. Surgical bypass of the
      duodenal obstruction significantly improved her symptoms. Replaced right hepatic
      artery related duodenal compression should be considered in the differential
      diagnosis of proximal duodenal obstruction. The presence of the replaced right
      hepatic artery should be clearly communicated to allow optimal presurgical
      planning. 

PMID- 24019117
TI  - Antimicrobial penetration in a dual-species oral biofilm after noncontact
      brushing: an in vitro study.
AB  - OBJECTIVES: Oral biofilm is inevitably left behind, even after powered brushing.
      As a special feature, powered brushing removes biofilm in a noncontact mode. When
      the brushing distance becomes too large, biofilm is left behind. We hypothesize
      that biofilm left behind after brushing has different viscoelastic properties
      than before brushing, impacting antimicrobial penetration. MATERIALS AND METHODS:
      In vitro grown dual-species biofilms were subjected to 20 % mechanical
      deformation before and after powered brushing at 4-mm brushing distance. Biofilm
      thickness and stress relaxation were measured for unbrushed and brushed biofilms.
      Stress relaxation was analyzed with a three-element Maxwell model. Antimicrobial
      penetration from five mouthrinses was microscopically evaluated for unbrushed and
      brushed biofilms. RESULTS: Thicknesses of unbrushed and brushed biofilms were
      similar. Brushing decreased the prevalence of fast and increased the prevalence
      of slow relaxation elements, which was accompanied by deeper penetration of
      chlorhexidine and cetylpyridinium chloride. Penetration of antimicrobials from
      other mouthrinses was relatively low in unbrushed and brushed biofilms.
      CONCLUSIONS: This confirmation of our hypothesis points to an additional
      advantage of powered toothbrushing in a noncontact mode, changing the
      viscoelastic properties of biofilm in a direction that increases antimicrobial
      penetration of chlorhexidine and cetylpyridinium. CLINICAL RELEVANCE: The biofilm
      left behind after noncontact powered toothbrushing may have less recalcitrance
      toward penetration of chlorhexidine and cetylpyridinium chloride than prior to
      brushing.

PMID- 24019118
TI  - Oleuropein and hydroxytyrosol activate GPER/ GPR30-dependent pathways leading to
      apoptosis of ER-negative SKBR3 breast cancer cells.
AB  - SCOPE: We have previously demonstrated that oleuropein (OL) and hydroxytyrosol
      (HT) reduce 17beta-estradiol-mediated proliferation in MCF-7 breast cancer (BC)
      cells without affecting the classical genomic action of estrogen receptor (ER),
      but activating instead the ERK1/2 pathway. Here, we hypothesized that this
      inhibition could be mediated by a G-protein-coupled receptor named GPER/GPR30.
      Using the ER-negative and GPER-positive SKBR3 BC cells as experimental model, we
      investigated the effects of OL and HT on GPER-mediated activation of downstream
      pathways. METHODS AND RESULTS: Docking simulations and ligand-binding studies
      evidenced that OL and HT are able to bind GPER. MTT cell proliferation assays
      revealed that both phenols reduced SKBR3 cell growth; this effect was abolished
      silencing GPER. Focusing on OL and HT GPER-mediated pathways, using Western blot
      analysis we showed a sustained ERK1/2 activation triggering an intrinsic
      apoptotic pathway. CONCLUSION: Showing that OL and HT work as GPER inverse
      agonists in ER-negative and GPER-positive SKBR3 BC cells, we provide novel
      insights into the potential of these two molecules as tools in the therapy of
      this subtype of BC.

PMID- 24019121
TI  - First line management of prolonged convulsive seizures in children and adults:
      good practice points.
AB  - Over the past decades, it has become clear that the most efficient way to prevent
      status epilepticus is to stop the seizure as fast as possible, and early
      treatment of prolonged convulsive seizures has become an integral part of the
      overall treatment strategy in epilepsy. Benzodiazepines are the first choice
      drugs to be used as emergency medication. This treatment in the early phases of a
      seizure often implies a 'pre-medical' setting before intervention of medically
      trained persons. In this paper, we propose "good practice points" for first line
      management of prolonged convulsive seizures in children and adults in a 'pre
      medical' setting. 

PMID- 24019122
TI  - Shape-selected colloidal MOF crystals for aqueous use.
AB  - Methods are described to synthesize shape-selectable, monodisperse, aqueous
      stable metal-organic frameworks (MOFs) by the reaction of aluminium nitrate with
      benzene tricarboxylic acid in various aqueous solvent mixtures and acetic acid as
      the capping ligand. Environmental stability was confirmed by thermal analysis and
      immersion in aqueous acidic media. 

PMID- 24019123
TI  - Quantifying the nature of lone pair domains.
AB  - The lone pair lies at the heart of chemistry, and is often in a conceptual
      respect the site of chemical reactivity. Here we show how the analysis of the
      electron localization function (ELF) can be improved upon by introducing intra
      basin partitioning. The high-ELF localization domain population (HELP), is
      presented as a probe of the more chemically relevant and electron-localized
      regions of the ELF lone pair basin, and shown to correlate with a range of
      physical properties and quantum mechanical constructs, such as the ESP, e and
      H(+) affinity, IP, HOMO/LUMO energies, atomic charge, NBO lone pair orbitals, and
      molecular geometry. A strong connection between topological density and orbital
      based analysis of chemistry is intuitively expected, yet this is the first time
      that an average electron population, obtained by any localization method, can be
      linked to properties of molecules. The application of HELP as a descriptor of
      lone pair domains is predicted to be of general use. 

PMID- 24019124
TI  - Confirmatory factor analytic structure and measurement invariance of quantitative
      autistic traits measured by the social responsiveness scale-2.
AB  - Understanding the factor structure of autistic symptomatology is critical to the
      discovery and interpretation of causal mechanisms in autism spectrum disorder. We
      applied confirmatory factor analysis and assessment of measurement invariance to
      a large (N = 9635) accumulated collection of reports on quantitative autistic
      traits using the Social Responsiveness Scale, representing a broad diversity of
      age, severity, and reporter type. A two-factor structure (corresponding to social
      communication impairment and restricted, repetitive behavior) as elaborated in
      the updated Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM
      5) criteria for autism spectrum disorder exhibited acceptable model fit in
      confirmatory factor analysis. Measurement invariance was appreciable across age,
      sex, and reporter (self vs other), but somewhat less apparent between clinical
      and nonclinical populations in this sample comprised of both familial and
      sporadic autism spectrum disorders. The statistical power afforded by this large
      sample allowed relative differentiation of three factors among items encompassing
      social communication impairment (emotion recognition, social avoidance, and
      interpersonal relatedness) and two factors among items encompassing restricted,
      repetitive behavior (insistence on sameness and repetitive mannerisms). Cross
      trait correlations remained extremely high, that is, on the order of 0.66-0.92.
      These data clarify domains of statistically significant factoral separation that
      may relate to partially-but not completely-overlapping biological mechanisms,
      contributing to variation in human social competency. Given such robust
      intercorrelations among symptom domains, understanding their co-emergence remains
      a high priority in conceptualizing common neural mechanisms underlying autistic
      syndromes. 

PMID- 24019125
TI  - Traumatic brain injury: guidance in a forensic context from outcome, dose
      response, and response bias research.
AB  - Traumatic brain injury (TBI) occurs at a high incidence, involving millions of
      individuals in the U.S. alone. Related to this, there are large numbers of
      litigants and claimants who are referred annually for forensic evaluation. In
      formulating opinions regarding claimed injuries, the present review advises
      experts to rely on two sets of information: TBI outcome and neuropsychological
      dose-response studies of non-litigants and non-claimants, and response bias
      literature that has demonstrated the relatively high risk of invalid responding
      among examinees referred within a secondary gain context, which in turn has
      resulted in the development of specific assessment methods. Regarding prospective
      methods for detecting possible response bias, both symptom validity tests, for
      measuring over-reporting of symptoms on inventories and questionnaires, and
      performance validity tests, for measuring insufficient effort on ability tests,
      are considered essential.

PMID- 24019126
TI  - Reduction in radiation-induced lymphocytopenia by famotidine in patients
      undergoing radiotherapy for prostate cancer.
AB  - BACKGROUND: Ionizing radiation causes a series of hematological alterations
      especially profound lymphocytopenia during and after the radiotherapy course. To
      investigate whether famotidine can reduce hematologic toxicity in patients
      treated with radiotherapy for prostate cancer. METHODS: A total of 36 patients
      undergoing radiotherapy for prostate cancer were randomized to receive either
      placebo or famotidine tablets. Participants were pretreated with 40 mg of oral
      famotidine or placebo tablets twice daily, 4 and 3 hr before each radiotherapy
      fraction. The patients received external-beam radiotherapy up to 70 Gy. Complete
      blood counts with differential, platelet counts, and hemoglobin levels were
      obtained at baseline, biweekly during the treatment and once 4 weeks after the
      end of radiotherapy course. Magnitude of changes from baseline in the
      hematological parameters was determined and compared using Repeated Measures
      ANOVA. RESULTS: Famotidine was well tolerated. A total of 112 blood samples were
      evaluated. A significant reduction in radiation-induced lymphocytopenia was noted
      in patients receiving famotidine than in patients receiving placebo (P = 0.006).
      No significant difference was observed between two groups for the decline in
      platelets, erythrocytes and leucocytes. For both groups, neutrophil, monocyte,
      eosinophil, and hemoglobin levels did not change significantly during the
      treatment. CONCLUSIONS: Our results indicate that famotidine could result in a
      significant reduction in radiation-induced lymphocytopenia and may consequently
      increase radiotherapy efficacy as well as survival times. This radioprotective
      effect may be chiefly associated with its antioxidant and radical scavenging
      properties. Further studies are required to confirm these encouraging results.

PMID- 24019127
TI  - Incidence of colorectal cancer after liver transplantation for primary sclerosing
      cholangitis: a systematic review and meta-analysis.
AB  - Patients with primary sclerosing cholangitis (PSC) and associated inflammatory
      bowel disease (IBD) have an increased risk of colorectal cancer (CRC). We
      estimated the pooled incidence of CRC after liver transplantation (LT) in
      patients with PSC as well as in a subset of patients with associated IBD (PSC
      IBD). Through a systematic review of major bibliographic databases up to April 1,
      2013, we identified cohort studies reporting the incidence of de novo CRC after
      LT for PSC. The main outcome measure was CRC incidence rate (IR) per 1000 person
      years after LT in all patients with PSC and in a subset of patients with PSC-IBD
      with an intact colon. According to a meta-analysis of 18 independent cohorts (69
      cases of CRC among 1987 patients), the pooled IR of de novo CRC in patients with
      PSC after LT was 5.8 per 1000 person-years [95% confidence interval (CI) = 3.8
      7.8]. According to a meta-analysis of 16 independent cohort studies (66 cases of
      CRC among 1017 patients), the IR of CRC in patients with PSC-IBD and an intact
      colon at the time of LT was 13.5 per 1000 person-years (95% CI = 8.7-18.2). A
      long duration of IBD and extensive colitis were identified as risk factors for
      CRC. Specific transplant-related factors that can increase the risk of CRC have
      not been identified. In conclusion, the risk of CRC remains high for patients who
      undergo LT for PSC, particularly in the subset of patients with associated IBD
      and an intact colon at the time of LT. Aggressive colonoscopic surveillance for
      CRC would be prudent for patients with PSC-IBD even after LT.

PMID- 24019128
TI  - Using the GO-FAR score.

PMID- 24019129
TI  - Mucosectom2-short blade for safe and efficient endoscopic submucosal dissection
      of colorectal tumors.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) in the colon
      has rapidly come into widespread use. However, as complications such as bleeding
      and perforation often occur, and the procedure time is longer for ESD than for
      endoscopic mucosal resection (EMR), development of safer and more reliable
      devices are required especially for colorectal ESD. We report on a new device,
      the Mucosectom2-short blade (M2-SB) for colorectal ESD and describe its safety
      and efficacy. PATIENTS AND METHODS: The study included 30 patients with lesions
      diagnosed as colorectal tumor: a nongranular-type laterally spreading tumor (LST)
      larger than 20 mm or a granular-type LST larger than 30 mm, or lesions that were
      evaluated as being difficult to remove even by piecemeal EMR. RESULTS: All
      lesions were resected en bloc using this new device, with free lateral and
      vertical margins. The procedure time was 61 minutes and there was no bleeding or
      perforation related to the procedure. CONCLUSION: The M2-SB seems to be a safe
      and efficient tool for colorectal ESD.

PMID- 24019130
TI  - Data quality of the German screening colonoscopy registry.
AB  - BACKGROUND AND STUDY AIMS: The German screening colonoscopy program is
      accompanied by a central registry that records the main outcome quality
      indicators, namely colonoscopy completion rate, adenoma detection rate (ADR), and
      complication rate. The aim of the present study was to assess the quality of
      these registry data by comparing them with data from a prospective quality
      assurance study based on a self-reporting audit and patient feedback of screening
      colonoscopy. PATIENTS AND METHODS: The completeness of registry information was
      analyzed by comparing it with prospective data gathered by audit and patient
      feedback in a previous quality assurance study (ClinicalTrials.gov registration
      number: NCT00860665) between October 2006 and March 2008. The main outcome
      parameters were colonoscopy completion rate, ADR, and complication rate.
      Complications were recorded in three steps in the audit study using case report
      forms (immediate and subsequent documentation by physicians [CRF-1 and CRF-2],
      and patient follow-up [CRF-3]), but were documented in the registry without
      differentiation. RESULTS: A total of 12 134 individuals (mean age 64.5 years; 47
      % men) who underwent screening colonoscopy at 19 private practices in Berlin over
      the 18-month period were included in the audit study. Patient feedback was
      obtained for 90.1 %. A total of 12 150 cases had been recorded in the registry by
      the same private practices during the same period. Colonoscopy completion rate
      and ADR data were comparable in the audit study and registry (completion rate
      98.2 % vs. 97.7 %; ADR 21.0 % vs. 20.5 %). However, compared with the registry
      data, the complication rate was 3.1-fold higher in the audit (0.46 % vs. 0.15 %;
      P < 0.001), and double (0.33 % vs. 0.15 %; P < 0.05) when patient feedback was
      not included. CONCLUSIONS: Of the screening colonoscopy quality parameters,
      colonoscopy completion rate and ADR, but not complication rates, were reliably
      documented in the German national screening colonoscopy registry. Data on
      complications need to be appropriately standardized and audited in order to be
      used for credentialing and benchmarking purposes.

PMID- 24019131
TI  - Quantitative elastography associated with endoscopic ultrasound for the diagnosis
      of chronic pancreatitis.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic ultrasonography (EUS) has become the method
      of choice for the diagnosis of chronic pancreatitis in clinical practice.
      However, the criteria allowing the specific diagnosis of the disease, mainly at
      non-advanced stages, are still under debate. Analysis of tissue stiffness by
      quantitative EUS-elastography may provide additional relevant information in this
      setting. The aim of this study was to evaluate the information provided by
      quantitative EUS-elastography for the diagnosis of chronic pancreatitis. PATIENTS
      AND METHODS: A prospective, consecutive, 1-year study was designed, and included
      patients who underwent EUS for epigastric pain syndrome or known chronic
      pancreatitis. EUS-elastography was performed using radial Pentax EUS and Hitachi
      EUB900. The strain ratio was measured in the head, body, and tail of the
      pancreas, and the elastographic result was the mean of these three values. EUS
      criteria of chronic pancreatitis and the Rosemont classification were also
      evaluated. Data were analyzed by analysis of variance and linear regression;
      diagnostic accuracy was based on the receiver operating characteristic (ROC)
      curve analysis. RESULTS: A total of 191 patients (mean age 52 years, range 21 -
      85; 103 male) were included; 92 (48.2 %) of them were finally diagnosed with
      chronic pancreatitis. A highly significant direct linear correlation was found
      between the number of EUS criteria of chronic pancreatitis and the strain ratio
      (r = 0.813; P < 0.0001). The area under the ROC curve was 0.949 (95 % confidence
      interval 0.916 - 0.982) and the accuracy of EUS-elastography for diagnosing
      chronic pancreatitis was 91.1 % (cut-off strain ratio of 2.25). The strain ratio
      varied significantly in different Rosemont classification groups (P < 0.001).
      CONCLUSIONS: EUS-elastography was an accurate tool for the diagnosis of chronic
      pancreatitis and provided relevant and objective information to support EUS
      findings.

PMID- 24019132
TI  - Nanoscale markers of esophageal field carcinogenesis: potential implications for
      esophageal cancer screening.
AB  - BACKGROUND AND STUDY AIMS: Esophageal adenocarcinoma (EAC) has a dismal prognosis
      unless treated early or prevented at the precursor stage of Barrett's esophagus
      associated dysplasia. However, some patients with cancer or dysplastic Barrett's
      esophagus (DBE) may not be captured by current screening and surveillance
      programs. Additional screening techniques are needed to determine who would
      benefit from endoscopic screening or surveillance. Partial wave spectroscopy
      (PWS) microscopy (also known as nanocytology) measures the disorder strength (Ld
      ), a statistic that characterizes the spatial distribution of the intracellular
      mass at the nanoscale level and thus provides insights into the cell nanoscale
      architecture beyond that which is revealed by conventional microscopy. The aim of
      the present study was to compare the disorder strength measured by PWS in normal
      squamous epithelium in the proximal esophagus to determine whether nanoscale
      architectural differences are detectable in the field area of EAC and Barrett's
      esophagus. METHODS: During endoscopy, proximal esophageal squamous cells were
      obtained by brushings and were fixed in alcohol and stained with standard
      hematoxylin and Cyto-Stain. The disorder strength of these sampled squamous cells
      was determined by PWS. RESULTS: A total of 75 patient samples were analyzed, 15
      of which were pathologically confirmed as EAC, 13 were DBE, and 15 were non
      dysplastic Barrett's esophagus; 32 of the patients, most of whom had reflux
      symptoms, acted as controls. The mean disorder strength per patient in
      cytologically normal squamous cells in the proximal esophagus of patients with
      EAC was 1.79-times higher than that of controls (P<0.01). Patients with DBE also
      had a disorder strength 1.63-times higher than controls (P<0.01). CONCLUSION:
      Intracellular nanoarchitectural changes were found in the proximal squamous
      epithelium in patients harboring distal EAC and DBE using PWS. Advances in this
      technology and the biological phenomenon of the field effect of carcinogenesis
      revealed in this study may lead to a useful tool in non-invasive screening
      practices in DBE and EAC.

PMID- 24019133
TI  - Yield of the second surveillance colonoscopy based on the results of the index
      and first surveillance colonoscopies.
AB  - BACKGROUND AND STUDY AIMS: The risk of advanced colorectal neoplasia (ACN) after
      the first surveillance colonoscopy is not well quantified. The aim of the current
      study was to quantify the risk of ACN on the second surveillance colonoscopy
      based on previous colonoscopic findings. PATIENTS AND METHODS: This was a single
      site study of patients with index adenomas who underwent two surveillance
      colonoscopies. ACN was defined as advanced adenoma (>= 1 cm, villous histology,
      or high-grade dysplasia) or as "high-risk" findings (advanced adenoma or >= 3 non
      advanced adenoma [NAA]). RESULTS: Among 509 patients with low-risk index
      findings, 61 (12.0 %; 95 % confidence interval [CI], 9.3 % - 15.1 %) had high
      risk findings on the first surveillance colonoscopy, 11 of whom (18.0 %; 95 %CI
      9.4 % - 30.0 %) had high-risk findings on second surveillance colonoscopy
      compared with 39 (8.7 %; 95 %CI 6.3 % - 11.7 %) of the remaining 448 patients who
      had normal or low-risk findings on the first surveillance colonoscopy (relative
      risk [RR] = 2.07; 95 %CI 1.12 - 3.83). Among 456 patients with high-risk index
      findings, 91 (20.0 %; 95 %CI 16.3 % - 23.9 %) had high-risk findings on the first
      surveillance colonoscopy, 20 of whom (22.0 %; 95 %CI 14.0 % - 31.9 %) had high
      risk findings on second surveillance colonoscopy compared with 40 (11.0 %; 95 %CI
      8.0 % - 146 %) of the remaining 365 patients who had normal or low-risk findings
      on first surveillance colonoscopy (RR = 2.01; 95 %CI 1.04 - 3.32). Results were
      similar when only advanced adenomas were considered. CONCLUSIONS: Patients with
      high-risk findings on index and first surveillance colonoscopies require close
      surveillance. Those with low-risk findings on index colonoscopy and normal/non
      advanced findings on the first surveillance colonoscopy have low subsequent risk
      of ACN. These and previous data may be useful for generating recommendations for
      the timing of the second surveillance colonoscopy.

PMID- 24019134
TI  - Argon plasma coagulation ablation versus endoscopic surveillance of Barrett's
      esophagus: late outcomes from two randomized trials.
AB  - BACKGROUND AND STUDY AIM: Argon plasma coagulation (APC) has been used to ablate
      dysplastic and nondysplastic Barrett's esophagus. We determined the longer-term
      efficacy of APC ablation within two randomized controlled trials of APC versus
      surveillance for Barrett's esophagus in patients in whom gastroesophageal reflux
      was controlled by either surgery or proton pump inhibitors. PATIENTS AND METHODS:
      129 patients (surgical trial 70, medical trial 59) with Barrett's esophagus
      (nondysplastic or low grade dysplasia) were randomly allocated to either ablation
      using APC or to continuing endoscopy surveillance. Outcomes were determined at
      three time points: short-term (12 months), mid-term (42-75 months) and long-term
      (> 84 months). RESULTS: In the APC groups, initial ablation of > 95 % of the
      Barrett's esophagus was achieved in 61 of 63 patients; the > 95 % ablation
      persisted in 47 of 56 patients at short-term follow-up, in 33 of 49 at mid-term
      and in 21 of 32 at long-term follow-up. In the surveillance groups, the length of
      Barrett's esophagus reduced from a mean of 4.2 cm to 2.7 cm at long-term follow
      up. High grade dysplasia (HGD) developed in 1 patient in the APC groups and in 3
      in the surveillance groups. Low grade dysplasia developed in 1 APC patient and in
      6 surveillance patients. CONCLUSIONS: APC ablation reduced the extent of
      Barrett's esophagus, and this reduction was maintained in some patients at longer
      term follow-up. However, progression to HGD can still occur despite APC ablation,
      suggesting endoscopic surveillance is still required. CLINICAL TRIAL
      REGISTRATION: ACTRN012607000293460 and ACTRN12607000292471 (Australian Clinical
      Trials Registry).

PMID- 24019135
TI  - Facile self-assembly synthesis of PdPt bimetallic nanotubes with good performance
      for ethanol oxidation in an alkaline medium.
AB  - PdPt bimetallic nanotubes were prepared by the self-assembly of Pt and Pd on Te
      nanowires at room temperature. The morphologies of the as-prepared PdPt nanotubes
      were investigated by scanning electron microscopy and transmission electron
      microscopy, and the results display a large amount of PdPt bimetallic nanotubes
      with a diameter of 10-20 nm and a length of several micrometers. The composition
      and structure of the nanotubes were characterized by X-ray diffraction, high
      resolution transmission electron microscopy, scanning transmission electron
      microscopy, and energy spectrum analysis, and the results display uniform
      compositional distributions of both elements (Pd and Pt). The mechanism of the
      formation of the nanotube structure was supposed. The electrocatalytic
      performance of PdPt nanotubes were studied by cyclic voltammetry and
      chronoamperometry. Electrochemical results show that the as-prepared PdPt
      nanotube catalysts have not only high activity but also good stability for
      ethanol oxidation in alkaline medium.

PMID- 24019138
TI  - Seasonal variations in the chemical composition of particulate matter: a case
      study in the Po Valley. Part I: macro-components and mass closure.
AB  - The seasonal variability in the mass concentration and chemical composition of
      atmospheric particulate matter (PM10 and PM2.5) was studied during a 2-year field
      study carried out between 2010 and 2012. The site of the study was the area of
      Ferrara (Po Valley, Northern Italy), which is characterized by frequent episodes
      of very stable atmospheric conditions in winter. Chemical analyses carried out
      during the study allowed the determination of the main components of atmospheric
      PM (macro-elements, ions, elemental carbon, organic matter) and a satisfactory
      mass closure was obtained. Accordingly, chemical components could be grouped into
      the main macro-sources of PM: soil, sea spray, inorganic compounds from secondary
      reactions, vehicular emission, organics from domestic heating, organics from
      secondary formation, and other sources. The more significant seasonal variations
      were observed for secondary inorganic species in the fine fraction of PM; these
      species were very sensitive to air mass age and thus to the frequency of stable
      atmospheric conditions. During the winter ammonium nitrate, the single species
      with the highest concentration, reached concentrations as high as 30 MUg/m(3).
      The intensity of natural sources was fairly constant during the year; increases
      in natural aerosols were linked to medium and long-range transport episodes. The
      ratio of winter to summer concentrations was roughly 2 for combustion product,
      close to 3 for secondary inorganic species, and between 2 and 3 for organics. The
      winter increase of organics was due to poorer atmospheric dispersion and to the
      addition of the emission from domestic heating. A similar winter to summer ratio
      (around 3) was observed for the fine fraction of PM.

PMID- 24019139
TI  - Leaching of heavy metals and alkylphenolic compounds from fresh and dried sewage
      sludge.
AB  - Reusing sewage sludge as a soil fertiliser has become a common alternative to
      disposal. Although this practice has a few benefits, it may contribute to the
      medium- and long-term contamination of the trophic chain because sewage sludge
      may contain heavy metals and organic contaminants. As the leaching of
      contaminants may depend on the sludge pre-treatment, the leaching of heavy metals
      (Cu, Ni, Pb, Zn and Cr) and alkylphenolic compounds (APCs) (octylphenol (OP),
      nonylphenol (NP), nonylphenol-mono-ethoxylate (NP1EO)) was investigated in five
      fresh and 40  degrees C dried sewage sludge samples from north-eastern Spain. FT
      IR analyses and full-scan GC-MS chromatograms showed that sludge drying changed
      the nature of organic compounds leading to changes in their solubility. Moreover,
      sludge drying led to a higher relative contribution of dissolved organic carbon
      than the particulate organic carbon in the leachates. Leaching of Pb, Zn and Cr
      was below 5 % in both fresh and dried sludge samples, whereas Cu and Ni leached
      at rates up to 12 and 43 %, respectively, in some of the dried sludge samples.
      The leaching yields of OP, NP and NP1EO ranged from 1.3 to 35 % for fresh
      samples, but they decreased from 0.8 to 3.4 % in dried samples. The decrease in
      the leachability of APCs observed in dried sludge samples might be attributed to
      the fact that these compounds are associated with particulate organic matter,
      with significantly lower concentration or even absent in dried sludge than in
      fresh sludge samples. Therefore, it is recommended to dry the sludge before its
      disposal.

PMID- 24019141
TI  - Photochemical behavior of fenpropathrin and lambda-cyhalothrin in solution.
AB  - The photodegradation processes of fenpropathrin and lambda-cyhalothrin were
      studied in hexane, methanol/water (1:1, v/v), and acetone in both ultraviolet
      light and simulated sunlight. Intermediates in the photodegradation process were
      identified using gas chromatography/mass spectrometry (GC/MS), and the analysis
      of intermediates was used to speculate on possible photodegradation pathways. The
      photodegradation processes of fenpropathrin and lambda-cyhalothrin followed
      pseudo first-order kinetics. The photodegradation rates varied according to the
      solvent in decreasing order: hexane>methanol/water (1:1, v/v)>acetone. The
      effects of substances coexisting in the environment on the photodegradation of
      pyrethroids were also investigated in the research. Acetone, humic acid, and
      riboflavin increased photodegradation rates while L-ascorbic acid slowed the
      process. This study provides a theoretical basis for the removal of pyrethroid
      pollution from the natural environment.

PMID- 24019140
TI  - Cardiovascular effects of arsenic: clinical and epidemiological findings.
AB  - Several population studies relate exposure to high levels of arsenic with an
      increased incidence of ischemic heart disease and cardiovascular mortality. An
      association has been shown between exposure to high levels of arsenic and
      cardiovascular risk factors such as hypertension and diabetes mellitus, and
      vascular damage such as subclinical carotid atherosclerosis. The mechanisms
      underlying these phenomena are currently being studied and appear to indicate an
      alteration of vascular function. However, the effects of low levels of exposure
      to arsenic and their potential detrimental cardiovascular effect are less
      explored. The article provides an overview of the pathophysiologic mechanisms
      linking low-level arsenic exposure to the occurrence of cardiovascular disease
      and its complications, and some potential preventive strategies to implement. 

PMID- 24019142
TI  - Adsorption and desorption of 2,4,6-trichlorophenol onto and from ash as affected
      by Ag(+), Zn (2+), and Al (3+).
AB  - Metal cations and organic pollutants mostly co-exist in the natural environment.
      However, their interactions in adsorption processes have yet to be adequately
      addressed. In the current study, the effect of inorganic cations with different
      charges (Ag(+), Zn(2+), and Al(3+)) on the adsorption and desorption of 2,4,6
      trichlorophenol (TCP) onto and from processed ash derived from wheat (Triticum
      aestivum L.) straw was investigated. The adsorption and desorption of TCP were
      both nonlinear; the isotherm and kinetics curves fitted well using the Freundlich
      equation and a pseudo-second-order model, respectively. The presence of Ag(+)
      promoted TCP adsorption, while Zn(2+) and Al(3+) reduced TCP adsorption onto ash.
      The desorption of TCP from ash showed obvious hysteresis, and the presence of
      Ag(+), Zn(2+), and Al(3+) caused the desorption to be less hysteretic. The
      suppression of TCP adsorption by Zn(2+) and Al(3+) was ascribed to the partial
      overlapping of adsorption groups between TCP and metal ions. Al(3+) had a
      stronger inhibition effect than that of Zn(2+) due to its higher binding capacity
      and larger hydrated ionic radius than those of Zn(2+). Enhanced adsorption of TCP
      onto ash by Ag(+) was ascribed to its ability to reduce the competitive
      adsorption of water molecules on ash surface by replacing the original ions, such
      as Na(+) and Ca(2+), and compressing the hydrated ionic radius of these metal
      ions. In addition, Ag(+) was able to bind with the aromatic organic compounds
      containing pi-electrons, which resulted in a further increase of TCP adsorption
      by ash. 

PMID- 24019143
TI  - Recovery approach affects soil quality in the water level fluctuation zone of the
      Three Gorges Reservoir, China: implications for revegetation.
AB  - Plants in the water level fluctuation zone of the Three Gorges Reservoir Region
      disappeared due to winter-flooding and prolonged inundation. Revegetation
      (plantation and natural recovery) have been promoted to restore and protect the
      riparian ecosystem in recent years. Revegetation may affect soil qualities and
      have broad important implications both for ecological services and soil recovery.
      In this study, we investigated soil properties including soil pH values, bulk
      density, soil organic matter (SOM), soil nutrients and heavy metals, soil
      microbial community structure, microbial biomass, and soil quality index under
      plantation and natural recovery in the Three Gorges Reservoir Region. Most soil
      properties showed significant temporal and spatial variations in both the
      plantation and natural recovery areas. Higher contents of SOM and NO3-N were
      found in plantation area, while higher contents of soil pH values, bulk density,
      and total potassium were observed in the natural recovery area. However, there
      were no significant differences in plant richness and diversity and soil
      microbial community structure between the two restoration approaches. A soil
      quality index derived from SOM, bulk density, Zn, Cd, and Hg indicated that
      natural recovery areas with larger herbaceous coverage had more effective
      capacity for soil restoration. 

PMID- 24019144
TI  - Relating sexual sadism and psychopathy to one another, non-sexual violence, and
      sexual crime behaviors.
AB  - Sexual sadism and psychopathy have been theoretically, clinically, and
      empirically linked to violence. Although both constructs are linked to predatory
      violence, few studies have sought to explore the covariation of the two
      constructs, and even fewer have sought to conceptualize the similarities of
      violence prediction in each. The current study considered all four Psychopathy
      Checklist-Revised (PCL-R) facets and employed well-defined, validated measures of
      sadism to elucidate the relation between sadism and psychopathy, as well as to
      determine the role of each in the prediction of non-sexual violence and sexual
      crime behaviors. Study 1 assessed 314 adult, male sex offenders using archival
      ratings, as well as the self-report Multidimensional Inventory of Development,
      Sex, and Aggression (the MIDSA). Study 2 used archival ratings to assess 599
      adult, male sex offenders. Exploratory and confirmatory factor analyses of crime
      scene descriptions yielded four sexual crime behavior factors: Violence, Physical
      Control, Sexual Behavior, and Paraphilic. Sadism and psychopathy covaried, but
      were not coextensive; sadism correlated with Total PCL-R, Facet 1, and Facet 4
      scores. The constructs predicted all non-sexual violence measures, but predicted
      different sexual crime behavior factors. The PCL-R facets collectively predicted
      the Violence and Paraphilic factors, whereas sadism only predicted the Violence
      factor.

PMID- 24019145
TI  - New Arabidopsis thaliana cytochrome c partners: a look into the elusive role of
      cytochrome c in programmed cell death in plants.
AB  - Programmed cell death is an event displayed by many different organisms along the
      evolutionary scale. In plants, programmed cell death is necessary for development
      and the hypersensitive response to stress or pathogenic infection. A common
      feature in programmed cell death across organisms is the translocation of
      cytochrome c from mitochondria to the cytosol. To better understand the role of
      cytochrome c in the onset of programmed cell death in plants, a proteomic
      approach was developed based on affinity chromatography and using Arabidopsis
      thaliana cytochrome c as bait. Using this approach, ten putative new cytochrome c
      partners were identified. Of these putative partners and as indicated by
      bimolecular fluorescence complementation, nine of them bind the heme protein in
      plant protoplasts and human cells as a heterologous system. The in vitro
      interaction between cytochrome c and such soluble cytochrome c-targets was
      further corroborated using surface plasmon resonance. Taken together, the results
      obtained in the study indicate that Arabidopsis thaliana cytochrome c interacts
      with several distinct proteins involved in protein folding, translational
      regulation, cell death, oxidative stress, DNA damage, energetic metabolism, and
      mRNA metabolism. Interestingly, some of these novel Arabidopsis thaliana
      cytochrome c-targets are closely related to those for Homo sapiens cytochrome c
      (Martinez-Fabregas et al., unpublished). These results indicate that the
      evolutionarily well-conserved cytosolic cytochrome c, appearing in organisms from
      plants to mammals, interacts with a wide range of targets on programmed cell
      death. The data have been deposited to the ProteomeXchange with identifier
      PXD000280. 

PMID- 24019146
TI  - Proteomic and virus-induced gene silencing (VIGS) Analyses reveal that gossypol,
      brassinosteroids, and jasmonic acid contribute to the resistance of cotton to
      Verticillium dahliae.
AB  - Verticillium wilt causes massive annual losses of cotton yield, but the mechanism
      of cotton resistance to Verticillium dahliae is complex and poorly understood. In
      this study, a comparative proteomic analysis was performed in resistant cotton
      (Gossypium barbadense cv7124) on infection with V. dahliae. A total of 188
      differentially expressed proteins were identified by mass spectrometry (MALDI
      TOF/TOF) analysis and could be classified into 17 biological processes based on
      Gene Ontology annotation. Most of these proteins were implicated in stimulus
      response, cellular processes and metabolic processes. Based on the proteomic
      analysis, several genes involved in secondary metabolism, reactive oxygen burst
      and phytohormone signaling pathways were identified for further physiological and
      molecular analysis. The roles of the corresponding genes were further
      characterized by employing virus-induced gene silencing (VIGS). Based on the
      results, we suggest that the production of gossypol is sufficient to affect the
      cotton resistance to V. dahliae. Silencing of GbCAD1, a key enzyme involving in
      gossypol biosynthesis, compromised cotton resistance to V. dahliae. Reactive
      oxygen species and salicylic acid signaling may be also implicated as regulators
      in cotton responsive to V. dahliae according to the analysis of GbSSI2, an
      important regulator in the crosstalk between salicylic acid and jasmonic acid
      signal pathways. Moreover, brassinosteroids and jasmonic acid signaling may play
      essential roles in the cotton disease resistance to V. dahliae. The
      brassinosteroids signaling was activated in cotton on inoculation with V. dahliae
      and the disease resistance of cotton was enhanced after exogenous application of
      brassinolide. Meanwhile, jasmonic acid signaling was also activated in cotton
      after inoculation with V. dahliae and brassinolide application. These data
      provide highlights in the molecular basis of cotton resistance to V. dahliae. 

PMID- 24019147
TI  - Identification of BZR1-interacting proteins as potential components of the
      brassinosteroid signaling pathway in Arabidopsis through tandem affinity
      purification.
AB  - Brassinosteroids (BRs) are essential phytohormones for plant growth and
      development. BRs are perceived by the cell surface receptor kinase BRI1, and
      downstream signal transduction through multiple components leads to activation of
      the transcription factors BZR1 and BZR2/BES1. BZR1 activity is highly controlled
      by BR through reversible phosphorylation, protein degradation, and
      nucleocytoplasmic shuttling. To further understand the molecular function of
      BZR1, we performed tandem affinity purification of the BZR1 complex and
      identified BZR1-associated proteins using mass spectrometry. These BZR1
      associated proteins included several known BR signaling components, such as BIN2,
      BSK1, 14-3-3lambda, and PP2A, as well as a large number of proteins with
      previously unknown functions in BR signal transduction, including the kinases
      MKK5 and MAPK4, histone deacetylase 19, cysteine proteinase inhibitor 6, a DEAD
      box RNA helicase, cysteine endopeptidases RD21A and RD21B, calmodulin-binding
      transcription activator 5, ubiquitin protease 12, cyclophilin 59, and
      phospholipid-binding protein synaptotagmin A. Their interactions with BZR1 were
      confirmed by in vivo and in vitro assays. Furthermore, MKK5 was found to
      phosphorylate BZR1 in vitro. This study demonstrates an effective method for
      purifying proteins associated with low-abundance transcription factors, and
      identifies new BZR1-interacting proteins with potentially important roles in BR
      response. 

PMID- 24019149
TI  - Healthy and unhealthy assimilation: country of origin and smoking behavior among
      immigrants.
AB  - Smoking rates in the country of origin were used to empirically examine whether
      immigrants converge toward natives' level of smoking prevalence with
      assimilation. Results show that assimilation is associated with a lower
      likelihood of ever quitting smoking for immigrants from countries with lower
      smoking rates relative to the USA and a higher likelihood for immigrants from
      countries with higher smoking rates, but for current or ever smoking, the
      estimated effects of assimilation are statistically insignificant. Although these
      findings demonstrate that health assimilation depends on the country of origin,
      the extent to which this pattern of assimilation is due to peer influence,
      differences in responsiveness to anti-smoking interventions such as taxes or
      smoke-free air restrictions, and/or other factors remains unclear because of the
      limitations of this study.

PMID- 24019148
TI  - Glycoproteome of elongating cotton fiber cells.
AB  - Cotton ovule epidermal cell differentiation into long fibers primarily depends on
      wall-oriented processes such as loosening, elongation, remodeling, and
      maturation. Such processes are governed by cell wall bound structural proteins
      and interacting carbohydrate active enzymes. Glycosylation plays a major role in
      the structural, functional, and localization aspects of the cell wall and
      extracellular destined proteins. Elucidating the glycoproteome of fiber cells
      would reflect its wall composition as well as compartmental requirement, which
      must be system specific. Following complementary proteomic approaches, we have
      identified 334 unique proteins comprising structural and regulatory families.
      Glycopeptide-based enrichment followed by deglycosylation with PNGase F and A
      revealed 92 unique peptides containing 106 formerly N-linked glycosylated sites
      from 67 unique proteins. Our results showed that structural proteins like
      arabinogalactans and carbohydrate active enzymes were relatively more abundant
      and showed stage- and isoform-specific expression patterns in the differentiating
      fiber cell. Furthermore, our data also revealed the presence of heterogeneous and
      novel forms of structural and regulatory glycoproteins. Comparative analysis with
      other plant glycoproteomes highlighted the unique composition of the fiber
      glycoproteome. The present study provides the first insight into the identity,
      abundance, diversity, and composition of the glycoproteome within single celled
      cotton fibers. The elucidated composition also indirectly provides clues about
      unicellular compartmental requirements underlying single cell differentiation. 

PMID- 24019150
TI  - Neurogastroenterology: Linaclotide and abdominal pain.

PMID- 24019152
TI  - IBD: a score to settle--measuring Crohn's disease activity.

PMID- 24019153
TI  - Chronic hepatitis D at a standstill: where do we go from here?
AB  - Immigration is fuelling a new reservoir of hepatitis D virus (HDV) in Europe, and
      hepatitis D still represents an important medical problem in the USA. The disease
      continues to be a major medical scourge in the developing world, in particular in
      countries such as Pakistan, Mongolia and Mauritania. New therapeutic strategies
      are being developed to disrupt interactions between HDV and its viral partner
      HBV, or with the host. Blocking or modifying the hepatitis B surface antigen
      (HBsAg) might interfere with the uptake or release of the hepatitis D virion;
      interference with host-mediated post-translational changes of proteins that are
      crucial to the HDV life cycle, such as prenylation, is another potential
      therapeutic option. At present, however, the only realistic option is to optimize
      IFN-alpha therapy. As eradication of HBsAg is the ultimate end point of therapy,
      long-term interferon administration might be required, raising an issue of
      tolerance in patients. Treatment with IFN-lambda is a potential alternative
      approach to IFN-alpha; treatment of hepatitis C with this cytokine seems to cause
      fewer adverse effects than IFN-alpha and, therefore, might be more suitable for
      long-term treatment of HDV.

PMID- 24019154
TI  - Gastrointestinal surgery: real-time tissue identification during surgery.

PMID- 24019151
TI  - Treatment decisions and contemporary versus pending treatments for hepatitis C.
AB  - The primary aim of antiviral therapy for chronic hepatitis C (CHC) is the
      prevention of progressive disease. A response to interferon (IFN) treatment is
      associated with an improvement in all-cause mortality and liver-related mortality
      from hepatitis C. Unless contraindicated, patients with CHC are thus potential
      candidates for treatment. Improved response rates are observed in patients with
      HCV genotype 1 infection treated with first-generation protease inhibitors.
      However, treatment with current first-generation protease inhibitors and IFN is
      complex and can result in appreciable adverse effects. The advent of potent, pan
      genotypic all-oral direct-acting antiviral (DAA) regimens necessitates a critical
      examination of the immediate application of PEG-IFN, ribavirin and DAA regimens
      in patients with CHC. Current guidelines and position statements do not make
      clear recommendations, and are behind the emerging data. Some aspects of the
      conundrums facing physicians and patients are summarized in this Review.
      Cirrhosis presents an immediate threat of disease, and ideally treatment should
      be targeted at those patients who have advancing or advanced disease;
      unfortunately, a disparity exists, as response rates are reduced in patients with
      cirrhosis and the risks of adverse events are increased. On balance, patients
      with mild disease could consider deferring treatment. 

PMID- 24019156
TI  - [In Process Citation].

PMID- 24019155
TI  - Hepatocellular carcinoma: How does keratin 19 influence HCC?

PMID- 24019157
TI  - [In Process Citation].

PMID- 24019159
TI  - Structure and distortion of lead fluoride nanocrystals in rare earth doped
      oxyfluoride glass ceramics.
AB  - A series of rare earth (RE) doped oxyfluoride glasses with the composition of (45
      x) SiO2-5Al2O3-40PbF2-10CdF2-xRe2O3 (x = 1, 5, 10, 15) (mol%) were prepared by a
      traditional melt-quenching method. Glass ceramics (GCs) were obtained after
      thermal treatment and characterized by X-ray diffraction (XRD) to investigate the
      nanocrystal structure and distortion. Both the dopant type and the doping level
      play an important role in the distortion of the PbF2-RE lattice. It is found that
      a cubic Pb3REF9 phase forms in low doping GCs, a tetragonal PbREF5 phase forms in
      middle doping GCs and cubic PbRE3F11 forms in high doping GCs. Accordingly, the
      site symmetry of RE(3+) dopants in beta-PbF2 nanocrystal undergoes a transition
      of Oh...D4h...Oh with the increase of doping level. The change in the ligands
      coordinating the RE(3+) ions was further illustrated by the optical changes in Yb
      doped GCs. This paper provides insights on the nanocrystal structure of RE at the
      atomic level and tries to make a complete description of the nanocrystal
      structure and distortion in these glass-ceramic materials, which will benefit the
      optimization of optical properties.

PMID- 24019158
TI  - Xenon-enhanced CT assessment of cerebral blood flow in stroke-in-progress
      patients with unilateral internal carotid artery or middle cerebral artery
      stenosis.
AB  - Carotid or cerebral artery stenosis resulting in low perfusion is a major cause
      of ischemic stroke. Understanding the unique hemodynamic features in each patient
      undergoing a stroke-in-progress (SIP) and the correlation between progression and
      cerebral blood flow (CBF) status would help in the diagnosis and treatment of
      individual patients. We used xenon-enhanced CT (Xe-CT) to examine cerebral
      perfusion in patients with or without SIP (30 patients/group), recruited from
      October 2009 to October 2010. Only SIP patients with unilateral stenosis in the
      internal or middle cerebral artery were recruited. The occurrence of watershed
      infarction was higher in the SIP group than in the non-SIP group (P <0.05). In
      the SIP group, larger hypoperfused areas were found around the lesions than in
      the non-SIP group. In the SIP group, the CBF values in the ipsilateral areas were
      significantly lower than those in corresponding regions on the contralateral
      side. CBF values in the contralateral hemisphere were significantly lower in the
      SIP group than in the non-SIP group. In SIP patients, infarctions were surrounded
      by larger hypoperfused areas than in non-SIP patients. These larger hypoperfused
      areas may result in pathological damage to the brain that is responsible for the
      progression of stroke. 

PMID- 24019160
TI  - Highly elastic and superstretchable graphene oxide/polyacrylamide hydrogels.

PMID- 24019161
TI  - Sequence diversity of sicG among group C and G Streptococcus dysgalactiae
      subspecies equisimilis isolates associated with human infections in western
      Norway.
AB  - Streptococcal inhibitor of complement (SIC) and distantly related to SIC (DRS)
      are well-characterized extracellular virulence factors produced by only a few emm
      types among group A streptococci. The prevalence and sequence variations of the
      sic-like gene (sicG) in clinical samples of group C and G Streptococcus
      dysgalactiae subspecies equisimilis (SDSE), however, have not been widely
      investigated. We constructed primers targeting sicG and screened 129
      geographically matched and previously emm-typed non-invasive (n = 64) and
      invasive (n = 65) SDSE isolates for the presence of this gene. sicG was detected
      in seven non-invasive and eight invasive isolates belonging to eight different
      emm types. Within five of these emm types, sicG-negative isolates were also
      detected. All three isolates of stG2078.0 possessed sicG and were associated with
      severe soft tissue infections. Altogether, six sicG alleles (sicG1-6) were
      identified, and sequence variations were mainly caused by single nucleotide
      polymorphisms and deletion/insertion mutations. sicG1-6 were predicted to encode
      SICG proteins of varying length, composition, and homology with SIC and DRS
      proteins of group A streptococci. Our findings indicate an unpredictable
      association between sicG and emm type, a limited distribution and substantial
      sequence diversity of sicG, and no obvious relation between its presence and
      disease severity.

PMID- 24019162
TI  - Identification of Haemophilus influenzae and Haemophilus haemolyticus by matrix
      assisted laser desorption ionization-time of flight mass spectrometry.
AB  - Generally accepted laboratory methods that have been used for decades do not
      reliably distinguish between H. influenzae and H. haemolyticus isolates. H.
      haemolyticus strains are often incorrectly identified as nontypeable Haemophilus
      influenzae (NTHi). To distinguish H. influenzae from H. haemolyticus we have
      created a new database on the matrix-assisted laser desorption ionization time-of
      flight mass spectrometry (MALDI-TOF MS) bio-typer 2 and compared the results with
      routine determination of Haemophilus (growth requirement for X and V factor), and
      multilocus sequence typing (MLST). In total we have tested 277 isolates, 244 H.
      influenzae and 33 H. haemolyticus. Using MLST as the gold standard, the agreement
      of MALDI-TOF MS was 99.6 %. MALDI-TOF MS allows reliable and rapid discrimination
      between H. influenzae and H. haemolyticus.

PMID- 24019166
TI  - Biochemist-tree: Using modular origami to understand the integration of
      intermediary metabolism.
AB  - Intermediary metabolism can be a complex area to study due to the inherent
      modularity of the catabolic biochemical processes. This article outlines a novel,
      cost-effective, and universally applicable teaching activity to enhance students
      understanding of the inter-relationship between the key processes of intermediary
      metabolism. A simple origami model, the "Biochemist-Tree" has been developed as a
      learning activity for intermediary metabolism, and its implementation was
      assessed. This modular origami model involves folding individual layers of the
      model, which must then be constructed into a "tree" with the metabolic process
      flowing correctly from macromolecules to ATP production from the electron
      transport chain/oxidative phosphorylation. Forty-eight students were provided
      with the activity as a revision tutorial exercise toward the end of a module on
      the introduction to biochemistry. The findings from this study show that the
      students found the activity to be interesting (>75%), scientifically useful
      (95%), and would recommend other students (85%) using this for their revision of
      catabolic metabolism. The novel nature of the exercise meant that it was engaging
      for the students and one that they also felt improved the understanding of the
      integration of the metabolic processes included. Further to being a one-off test
      of student understanding, the inclusion of key molecular structures and pathway
      steps helps to further embed these as a reference sources for revision.

PMID- 24019163
TI  - Multi-center evaluation of the VITEK(r) MS system for mass spectrometric
      identification of non-Enterobacteriaceae Gram-negative bacilli.
AB  - Studies have demonstrated that matrix-assisted laser desorption ionization time
      of-flight mass spectrometry (MALDI-TOF MS) is a rapid, accurate method for the
      identification of clinically relevant bacteria. The purpose of this study was to
      evaluate the performance of the VITEK MS v2.0 system (bioMerieux) for the
      identification of the non-Enterobacteriaceae Gram-negative bacilli (NEGNB). This
      multi-center study tested 558 unique NEGNB clinical isolates, representing 18
      genera and 33 species. Results obtained with the VITEK MS v2.0 were compared with
      reference 16S rRNA gene sequencing and when indicated recA sequencing and
      phenotypic analysis. VITEK MS v2.0 provided an identification for 92.5 % of the
      NEGNB isolates (516 out of 558). VITEK MS v2.0 correctly identified 90.9 % of
      NEGNB (507 out of 558), 77.8 % to species level and 13.1 % to genus level with
      multiple species. There were four isolates (0.7 %) incorrectly identified to
      genus level and five isolates (0.9 %), with one incorrect identification to
      species level. The remaining 42 isolates (7.5 %) were either reported as no
      identification (5.0 %) or called "mixed genera" (2.5 %) since two or more
      different genera were identified as possible identifications for the test
      organism. These findings demonstrate that the VITEK MS v2.0 system provides
      accurate results for the identification of a challenging and diverse group of
      Gram-negative bacteria.

PMID- 24019167
TI  - An interwoven metal-organic framework combining mechanically interlocked linkers
      and interpenetrated networks.
AB  - New dibenzo[24]crown-8 ether derivatives were prepared that contain appendages
      with thioether donors that can coordinate to a metal ion. These macrocycles were
      then combined with 1,2-bis(pyridinium) ethane axles to create two types of
      [2]rotaxane ligands; those with the four thioether donors on the crown ether and
      those with six donor groups, four from the crown ether and two more attached to
      the stoppering groups of the dumbbell. The crown ethers and both types of
      [2]rotaxane ligands were allowed to react with Ag(I) ions to form metal-organic
      rotaxane framework (MORF) style coordination polymers. The interlocked
      hexadentate ligand forms the first example of a new type of lattice containing
      interwoven frameworks resulting from both interpenetration of frameworks due to
      the presence of an interlocked ligand and more classical interpenetration of
      independent frameworks. 

PMID- 24019168
TI  - PubMed search strings for the study of agricultural workers' diseases.
AB  - BACKGROUND: Several optimized search strategies have been developed in Medicine,
      and more recently in Occupational Medicine. The aim of this study was to identify
      efficient PubMed search strategies to retrieve articles regarding putative
      occupational determinants of agricultural workers' diseases. METHODS: We selected
      the Medical Subjects Heading (MeSH) term agricultural workers' diseases and six
      MeSH terms describing farm work (agriculture, agrochemicals NOT pesticides,
      animal husbandry, pesticides, rural health, rural population) alongside 61 other
      promising terms. We estimated proportions of articles containing potentially
      pertinent information regarding occupational etiology to formulate two search
      strategies (one "more specific," one "more sensitive"). We applied these
      strategies to retrieve information on the possible occupational etiology among
      agricultural workers of kidney cancer, knee osteoarthritis, and multiple
      sclerosis. We evaluated the number of needed to read (NNR) abstracts to identify
      one potentially pertinent article in the context of these pathologies. RESULTS:
      The "more specific" search string was based on the combination of terms that
      yielded the highest proportion (40%) of potentially pertinent abstracts. The
      "more sensitive" string was based on use of broader search fields and additional
      coverage provided by other search terms under study. Using the "more specific"
      string, the NNR to find one potentially pertinent article were: 1.1 for kidney
      cancer; 1.4 for knee osteoarthritis; 1.2 for multiple sclerosis. Using the
      sensitive strategy, the NNR were 1.4, 3.6, and 6.3, respectively. CONCLUSION: The
      proposed strings could help health care professionals explore putative
      occupational etiology for agricultural workers' diseases (even if not generally
      thought to be work related).

PMID- 24019169
TI  - How important is acute cellular rejection?

PMID- 24019170
TI  - NKG2D regulates production of soluble TRAIL by ex vivo expanded human gammadelta
      T cells.
AB  - Soluble TRAIL (sTRAIL) can be produced by myeloid-derived cells to kill cancer
      cells. Whether this mechanism is used by T cells, and if so, how sTRAIL
      production is regulated, remains unclear. Our previous studies showed that ex
      vivo expanded human gammadelta T cells express TRAIL and NK receptor group 2
      (R2), member D (NKG2D), and possess potent anticancer activities both in vitro
      and in vivo. Here, we investigated in greater detail the mechanisms by which
      gammadelta T cells utilize TRAIL and NKG2D to kill lung cancer cells. We
      demonstrate that human lung cancer cells express TRAIL R2 and NKG2D ligands.
      Blocking TRAIL or NKG2D during gammadelta T-cell-lung cancer cell co-cultures
      significantly reduced gammadelta T-cell-mediated cytotoxicity. Cross-linking
      NKG2D with anti-NKG2D antibody to mimic ligand binding promoted gammadelta T
      cells to produce sTRAIL, which induced apoptosis in lung cancer cells through
      TRAIL R2. Either neutralizing sTRAIL or blocking lung cancer cell TRAIL R2
      significantly reduced gammadelta T-cell-mediated cytotoxicity to lung cancer
      cells. This study demonstrates that gammadelta T cells can mediate anticancer
      immunity via NKG2D-regulated production of sTRAIL. 

PMID- 24019171
TI  - Augmentation of venous outflow for salvage of a combined anterolateral thigh,
      tensor fasciae latae, and rectus femoris free flap used for abdominal wall
      reconstruction.

PMID- 24019172
TI  - Tertiary breast reconstruction using a free contralateral latissimus dorsi
      musculocutaneous flap.

PMID- 24019173
TI  - Varicose peroneal veins in fibula free flaps.

PMID- 24019174
TI  - A simple cost-effective method of microsurgical simulation training: the turkey
      wing model.
AB  - The rat femoral artery (RFA) anastomosis model has been the gold standard in
      microsurgical simulation training. While effective, live animal use requires
      animal use committee regulation and costly maintenance. Our institution's animal
      laboratory is remote to the hospital, limiting access by our busy surgical
      residents with their limited duty hours. We present an alternative convenient,
      cost-effective model. Ten frozen turkey wings were divided into distal and
      proximal segments. Vessel diameter, length, and anastomosis perfusion were
      assessed. Proximal brachial arteries ("humeral" segments) measured 8.85 +/- 1.14
      cm long with diameter 1.69 +/- 0.27 mm. Distal brachial arteries ("forearm")
      measured 10.5 +/- 2.06 cm long with diameter 1.25 +/- 0.25 mm. An 8-lb box (~20
      wings) cost $13.76. Separate use of the segments provides two training sessions
      with $0.35 per session effective cost. Our average cost for RFA microsurgical
      training sessions was $120 dollars for a single rat 2-hour session and $66 per
      rat if a maximum crate load of six rats was used. Besides significant cost, not
      all training programs are equipped to house, care for, and use rats in
      microsurgical training. We now use turkey wings for microvascular training. They
      are cheap, abundant, readily accessible for training, and consistent with tissue
      quality and vessel size approximating human systems.

PMID- 24019175
TI  - The use of magnetic resonance angiography in vascularized groin lymph node
      transfer: an anatomic study.
AB  - Vascularized groin lymph node transfer (VGLNT) has been successfully used to
      treat lymphedema. However, lack of familiarity with the inguinal node anatomy and
      concerns regarding donor site morbidity have limited its widespread use. The
      purpose of this study was to use magnetic resonance angiography (MRA) to clarify
      the inguinal anatomy and provide a reliable method for identifying the location
      of the superficial transverse inguinal lymph nodes. In this study MRA was used to
      evaluate the superficial inguinal lymph nodes in 117 patients. Coordinates of
      lymph nodes were plotted relative to an axis from the anterior superior iliac
      spine (ASIS) to the pubic tubercle (PT). The nodes were also plotted relative to
      the superficial circumflex iliac vein (SCIV) and superficial inferior epigastric
      vein (SIEV). A total of 1,938 lymph nodes were identified. These lymph nodes were
      concentrated on one-third the distance from the PT toward the ASIS and 3 cm
      perpendicularly below this line. About 67% of the superficial inguinal nodes were
      located within the bifurcation of the SIEV and SCIV. The results from this study
      provide useful guidelines for locating lymph nodes targeted for VGLNT. 

PMID- 24019176
TI  - Nerve transfers for shoulder function for traumatic brachial plexus injuries.
AB  - The objective of this article was to evaluate the clinical results of nerve
      transfer procedures for the restoration of shoulder abduction and external
      rotation in patients with traumatic brachial plexus injuries. A retrospective
      study was done to determine the results of nerve transfers for shoulder function
      in patients with traumatic brachial plexus injuries. The authors evaluated
      shoulder abduction and external rotation in terms of type of nerve transfer
      performed (single vs. double) and the time delay to surgery (greater or less than
      6 mo). A total of 20 patients were evaluated with 5 patients having double nerve
      transfers and 15 patients having single nerve transfers to restore shoulder
      function. All surgeries were done within 12 months of injury. The average follow
      up for the 20 patients was 28.4 +/- 17.5 months (minimum of 12 mo follow-up for
      all patients). The mean shoulder abduction and external rotation for the single
      nerve transfer group was 71.3 +/- 48 degrees and 56 +/- 44 degrees, respectively.
      For the double nerve transfer group, the mean shoulder abduction and external
      rotation was 123 +/- 49 degrees and 86 +/- 35 degrees, respectively. The
      difference was significant for the shoulder abduction (p = 0.05) but not for the
      external rotation (p = 0.19). In terms of time delay to surgery, there was no
      difference between surgery done in 6 months or less versus those done greater
      than 6 months but less than 12 months for shoulder abduction (88.1 +/- 47.7
      degrees and 77.1 +/- 63.4 degrees, respectively, p = 0.67) and shoulder external
      rotation (63.8 +/- 42.2 degrees and 62.8 +/- 49.3 degrees, respectively, p =
      0.96). The results of this study showed that nerve transfers can restore
      functional shoulder abduction and external rotation. Double nerve transfers tend
      to have significantly greater range of shoulder abduction compared with single
      nerve transfers if done within 1 year of injury.

PMID- 24019177
TI  - Free tissue transfer in patients with severe peripheral arterial disease:
      functional outcome in reconstruction of chronic lower extremity defects.
AB  - Chronic wounds of the lower extremity are difficult to treat, especially in
      patients with peripheral arterial disease (PAD). This patient population
      frequently suffers from multiple comorbidities, which further impairs wound
      healing. Local flaps are often not available, or are insufficient to cover these
      defects, and limbs are frequently amputated, although they could possibly be
      salvaged by free tissue transplantation. Although there is a growing evidence
      that free tissue transfer may be feasible in these patients with otherwise doomed
      extremities, previous studies have mostly focused on short-term flap survival,
      but not long-term ambulatory status and independence. Therefore, we investigated
      the long-term results of limb salvage, ambulatory status, and social independence
      in patients with PAD who underwent free tissue transfer for chronic wounds of the
      lower extremities.In this study we retrospectively reviewed 38 patients who
      underwent free tissue transfer because of nontraumatic, chronic wounds of the
      lower extremities at our institution. All patients suffered from a nontraumatic
      occlusion of at least one major lower leg artery verified by angiography. After a
      mean time period of 34 months we assessed flap survival and limb preservation as
      well as pre- and postoperative ambulatory status and social independence. A
      subgroup of 14 patients with a "single-vessel-leg" was evaluated separately.It
      was observed that anterolateral thigh and latissimus dorsi musculocutaneous flaps
      were most often used to cover the defects. Overall 29 out of the 38 flaps healed
      completely (9 flap failures) and 34 extremities were salvaged, including 12 out
      of 14 single-vessel-legs. One patient had to be amputated despite a vital free
      flap because of persistent calcaneal osteomyelitis. After failure of free tissue
      transfer, six extremities could still be salvaged by secondary procedures (two
      secondary free flaps, two local flaps, and two skin grafts). Total 22 out of 34
      patients with salvaged limbs maintained or improved their ambulatory status. In
      the amputee group, two patients remained on their preoperative level of mobility,
      while two declined. All patients with amputated limbs required assistance in
      activities of daily living while this was only true for 4 out of the 34 remaining
      patients.It was concluded that free tissue transfer is a valid option for
      salvaging lower extremities in patients with PAD. Long-term limb salvage can be
      achieved in a high percentage of cases, which allows the patients to ambulate
      freely and remain socially independent. 

PMID- 24019178
TI  - Efficiency roll-off in organic light-emitting diodes.
AB  - Organic light-emitting diodes (OLEDs) have attracted much attention in research
      and industry thanks to their capability to emit light with high efficiency and to
      deliver high-quality white light that provides good color rendering. OLEDs
      feature homogeneous large area emission and can be produced on flexible
      substrates. In terms of efficiency, OLEDs can compete with highly efficient
      conventional light sources but their efficiency typically decreases at high
      brightness levels, an effect known as efficiency roll-off. In recent years, much
      effort has been undertaken to understand the underlying processes and to develop
      methods that improve the high-brightness performance of OLEDs. In this review, we
      summarize the current knowledge and provide a detailed description of the
      relevant principles, both for phosphorescent and fluorescent emitter molecules.
      In particular, we focus on exciton-quenching mechanisms, such as triplet-triplet
      annihilation, quenching by polarons, or field-induced quenching, but also discuss
      mechanisms such as changes in charge carrier balance. We further review methods
      that may reduce the roll-off and thus enable OLEDs to be used in high-brightness
      applications. 

PMID- 24019179
TI  - Tobacco use among long-term survivors of head and neck cancer treated with
      radiation therapy.
AB  - PURPOSE: The objective of this study is to determine the prevalence of tobacco
      consumption (i.e., cigarette use) among survivors of head and neck cancer after
      treatment with radiation therapy (RT). METHODS AND MATERIALS: A longitudinal
      study was conducted with 230 patients previously treated with RT for squamous
      cell carcinoma of the head and neck. All patients were clinically without
      evidence of disease and had a minimum of 1 year follow-up. Patients were
      summarily asked about the use of tobacco products at each follow-up visit. To
      explore for associations between potential predictors of post-RT smoking, the Chi
      square test and Spearman's correlation coefficient were employed. RESULTS: The
      percentage of patients who were actively smoking was 21%, 21%, and 20%, at 1, 2,
      and 3 years post-RT, respectively. When the analysis was limited to patients with
      a former smoking history (i.e., excluding all never-smokers), these percentages
      increased to 32%, 27%, and 25%, respectively. The intensity of smoking at follow
      up ranged from one cigarette daily to 2.5 packs daily. Forty-two of 76 (55%)
      patients who were smoking at diagnosis were found to be smoking at 1-year follow
      up compared to 7 of 154 patients who were not (p < 0.001). The only factor that
      significantly predicted for persistent smoking at follow-up was the presence of a
      preexisting psychiatric condition (most commonly, a mood disorder) at initial
      cancer diagnosis. CONCLUSIONS: A significant proportion of former smokers are
      actively smoking during follow-up despite having completed intensive RT and
      having their cancers evidently under control. Innovative interventional
      approaches to target those at highest risk for continued smoking are warranted.

PMID- 24019180
TI  - Immunotherapy for acne vulgaris: current status and future directions.
AB  - There is a high unmet clinical need for new and better treatments in acne
      vulgaris. Propionibacterium acnes has a strong proinflammatory activity and
      targets molecules involved in the innate cutaneous immunity, keratinocytes and
      sebaceous glands of the pilosebaceous follicle. The role of P. acnes in acne
      confers legitimacy on the possible benefits of immunization-based approaches,
      which may represent a solution for limiting the development of antibiotic
      resistant P. acnes. Various immunization-based approaches have been developed
      over the last decades, including killed pathogen-based vaccines, vaccination
      against cell wall-anchored sialidase, monoclonal antibodies to the Christie,
      Atkins, Munch-Peterson factor of P. acnes, anti-Toll-like receptors vaccines and
      natural antimicrobial peptides. This review summarizes the current evidence and
      explores the challenges to making this a realistic treatment option for the
      future. 

PMID- 24019181
TI  - Lentigo maligna: review of salient characteristics and management.
AB  - Lentigo maligna is a melanocytic neoplasm, often regarded as 'melanoma in situ,'
      which may progress to lentigo maligna melanoma. Lentigo maligna clinically
      presents as a pigmented, asymmetric macule that originates on the head and neck
      and spreads slowly. The preferred method for diagnosing lentigo maligna is
      excisional biopsy. Histology shows proliferation of atypical melanocytes at the
      epidermal-dermal junction in small nests or single cells. The differential
      diagnosis includes solar lentigo, seborrheic keratosis, lichen planus-like
      keratosis, pigmented actinic keratosis, and melanocytic nevus. Stains used in
      diagnosis include hematoxylin and eosin, HMB-45, MART-1/Melan-A, Mel-5, and S
      100. Surgical excision is the preferred treatment for lentigo maligna. Second
      line techniques include medical (topical imiquimod) and destructive therapy. 

PMID- 24019182
TI  - An in situ FTIR spectroscopic study of the electrochemical oxidation of ethanol
      at a Pb-modified polycrystalline Pt electrode immersed in aqueous KOH.
AB  - A study of the mechanism of ethanol oxidation in alkaline solution on a platinum
      electrode modified with an irreversibly-deposited layer of lead has been carried
      out using in situ FTIR spectroscopy. This study provides support for the
      suggestion that the adsorption mechanism of ethanol is substantially modified in
      the presence of Pb, with a carbon-bonded intermediate being favoured leading to
      facile scission of the C-C bond in ethanol. We have found that the formation of
      carbonate takes place at potentials close to the thermodynamic value. At higher
      potentials, when Pb is lost to solution, the mechanism of oxidation of ethanol
      reverts to that found on a normal polycrystalline Pt surface, with the primary
      product being acetate. 

PMID- 24019183
TI  - Assessment of efficacy, safety and quality of life of 55 patients with metastatic
      renal cell carcinoma treated with temsirolimus: a single-center experience in
      Japan.
AB  - BACKGROUND: To evaluate experience of the use of temsirolimus for metastatic
      renal cell carcinoma (mRCC) in a single center in Japan. METHODS: This study
      included 55 consecutive patients with mRCC who received temsirolimus in a routine
      clinical setting, and retrospectively reviewed the comprehensive outcomes of
      these patients. RESULTS: Of the 55 patients, 20 had a Karnofsky performance
      status of <=80, and 5, 41 and 9 were classified into favorable, intermediate and
      poor risk groups, respectively, according to the Memorial Sloan-Kettering Cancer
      Center model. Initially, 25 mg of temsirolimus was applied weekly; however, dose
      modification was required in 19 patients, resulting in a relative dose intensity
      of 90.5 % throughout this series. As the best responses to temsirolimus, 4, 44
      and 7 were judged to have a partial response, stable disease and progressive
      disease, respectively. The median progression-free survival (PFS) and overall
      survival (OS) of these patients following the introduction of temsirolimus was
      7.0 and 25.0 months, respectively. Of several factors examined, only the
      pretreatment C-reactive protein level was shown to be independently associated
      with both PFS and OS. The common adverse events related to temsirolimus
      corresponding to >=grade 3 were anemia in 4, thrombocytopenia in 3, stomatitis in
      3 and hyperglycemia in 3. Quality of life analysis using 36-Item Short Form
      showed that there were no significant differences in any scale scores between
      surveys performed before and 3 months after the introduction of temsirolimus.
      CONCLUSIONS: Temsirolimus was well tolerated and facilitated comparatively
      favorable cancer control in Japanese patients with mRCC.

PMID- 24019184
TI  - Resident's morning report: an opportunity to reinforce principles of biomedical
      science in a clinical context.
AB  - The principles of biochemistry are core to understanding cellular and tissue
      function, as well as the pathophysiology of disease. However, the clinical
      utility of biochemical principles is often obscure to clinical trainees.
      Resident's Morning Report is a common teaching conference in which residents
      present clinical cases of interest to a faculty member for discussion. This venue
      provides an opportunity to illustrate how basic biomedical principles facilitate
      an understanding of the clinical presentation, the relevant pathophysiology, and
      the rationale for diagnostic and therapeutic strategies. A discussion of
      biochemical principles can easily be incorporated into these case discussions,
      with the potential to reinforce these concepts and to illustrate their
      application to clinical decision making. This approach maintains the effort to
      teach basic biomedical sciences in the context of clinical application across the
      educational continuum.

PMID- 24019185
TI  - Outcomes for recipients of liver transplantation for alpha-1-antitrypsin
      deficiency-related cirrhosis.
AB  - Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disease caused by an
      abnormal production of the serine protease inhibitor AAT. Liver transplantation
      (LT) cures cirrhosis caused by AAT deficiency and restores the normal production
      of AAT. There are few reports on the post-LT outcomes of patients with AAT
      deficiency. The aim of this study was to determine the characteristics and
      outcomes of patients undergoing LT for AAT deficiency at 3 large transplant
      centers. All patients undergoing LT at these 3 transplant centers from 1987 to
      2012 for AAT deficiency (ZZ or SZ phenotype) were included. The most recent 50
      patients with the MZ phenotype were also included for comparison. Data were
      collected retrospectively from internal databases and medical records. Seventy
      three patients (50 with the ZZ phenotype and 23 with the SZ phenotype)underwent
      LT. The mean age was 52.8 years, and the majority of the patients (75.6%) were
      men. Before LT, serum AAT levels were lower for the ZZ patients versus the SZ
      patients (28.3 versus 58.0 mg/dL, P < 0.001). More than 40% of the SZ patients
      had an additional liver disease, whereas 8% in the ZZ group and 90% in the MZ
      group did. Before LT, there was no significant difference in pulmonary function
      between the ZZ and SZ groups. Seventeen patients (all with ZZ phenotype)had
      pulmonary function tests performed before and after LT. The forced expiratory
      volume in 1 second (FEV1) continued to decline for the majority. The 1-, 3-, 5-,
      and 10-year post-LT survival rates were 86%, 83%, 80%, and 72%, respectively, for
      the ZZ patients and 91%, 86%, 79%, and 79%, respectively, for the SZ patients. In
      conclusion, survival after LT for patients with ZZ or SZ AAT deficiency is
      excellent. Despite the normalization of AAT levels after LT, FEV1 continues to
      decline unexpectedly after LT in some ZZ and SZ patients.

PMID- 24019188
TI  - Metabolism of norethisterone in the greyhound.
AB  - RATIONALE: Norethisterone has been used as a successful oral contraceptive in
      humans for many years. It was recently permitted for use as an oestrus
      suppressant in racing greyhounds. To monitor the use of norethisterone as part of
      a routine drug surveillance programme, knowledge of its metabolism was required
      to enable detection. METHODS: Gas chromatography/mass spectrometry and selective
      derivatisation techniques have been used to identify urinary metabolites of
      norethisterone following oral administration to the greyhound. Metabolites were
      extracted using solid-phase and liquid-liquid extraction techniques. RESULTS:
      Several metabolites were identified, including reduced, mono-, di- and
      trihydroxylated steroids. The major metabolites observed were 17alpha-ethynyl
      5beta-estrane-3alpha,17beta-diol, 17alpha-ethynyl-5alpha-estrane-3beta,17beta
      diol, three 17alpha-ethynylestranetriol stereoisomers and two 17alpha
      ethynylestranetetrol stereoisomers. The major metabolites were predominantly
      excreted as glucuronic acid conjugates and detection of the administration of
      norethisterone was possible for up to 8 days post-dose using the methods
      described. The nandrolone metabolites, 19-norepiandrosterone, estranediol and 19
      noretiocholanolone, were also identified in the post-administration samples
      collected up to 8 h after dosing the treated animals. CONCLUSIONS: The urinary
      metabolites identified in this study have further increased the knowledge of
      steroid metabolism in the greyhound, providing information to support routine
      drug testing programmes for greyhound racing.

PMID- 24019186
TI  - DXA and pQCT predict pertrochanteric and not femoral neck fracture load in a
      human side-impact fracture model.
AB  - The validity of dual energy X-ray absorptiometry (DXA) and peripheral
      quantitative computed tomography (pQCT) measurements as predictors of
      pertrochanteric and femoral neck fracture loads was compared in an experimental
      simulation of a fall on the greater trochanter. 65 proximal femora were harvested
      from patients at autopsy. All specimens were scanned with use of DXA for areal
      bone mineral density and pQCT for volumetric densities at selected sites of the
      proximal femur. A three-point bending test simulating a side-impact was performed
      to determine fracture load and resulted in 16 femoral neck and 49 pertrochanteric
      fractures. Regression analysis revealed that DXA BMD trochanter was the best
      variable at predicting fracture load of pertrochanteric fractures with an
      adjusted R(2) of 0.824 (p < 0.0001). There was no correlation between
      densitometric parameters and the fracture load of femoral neck fractures. A
      significant correlation further was found between body weight, height, femoral
      head diameter, and neck length on the one side and fracture load on the other
      side, irrespective of the fracture type. Clinically, the DXA BMD trochanter
      should be favored and integrated routinely as well as biometric and geometric
      parameters, particularly in elderly people with known osteoporosis at risk for
      falls.

PMID- 24019189
TI  - Characterizing the isotopic composition of atmospheric ammonia emission sources
      using passive samplers and a combined oxidation-bacterial denitrifier approach.
AB  - RATIONALE: Ammonia (NH3) emissions are a substantial source of nitrogen pollution
      to sensitive terrestrial, aquatic, and marine ecosystems and dependable
      quantification of NH3 sources is of growing importance due to recently observed
      increases in ammonium (NH4(+)) deposition rates. While determination of the
      nitrogen isotopic composition of NH3 (delta(15)N-NH3) can aid in the
      quantification of NH3 emission sources, existing methods have precluded a
      comprehensive assessment of delta(15)N-NH3 values from major emission sources.
      METHODS: We report an approach for the delta(15)N-NH4(+) analysis of low
      concentration NH4(+) samples that couples the bromate oxidation of NH4(+) to NO2(
      ) and the microbial denitrifier method for delta(15)N-NO2(-) analysis. This
      approach reduces the required sample mass by 50-fold relative to standard
      elemental analysis (EA) procedures, is capable of high throughput, and eliminates
      toxic chemicals used in a prior method for the analysis of low concentration
      samples. Using this approach, we report a comprehensive inventory of delta(15)N
      NH3 values from major emission sources (including livestock operations, marine
      sources, vehicles, fertilized cornfields) collected using passive sampling
      devices. RESULTS: The delta(15)N-NH4(+) analysis approach developed has a
      standard deviation of +/-0.70/00 and was used to analyze passively collected NH3
      emissions with a wide range of ambient NH3 concentrations (0.2 to 165.6 ug/m(3)).
      The delta(15)N-NH3 values reveal that the NH3 emitted from volatilized livestock
      waste and fertilizer has relatively low delta(15)N values (-56 to -230/00),
      allowing it to be differentiated from NH3 emitted from fossil fuel sources that
      are characterized by relatively high delta(15)N values (-15 to +20/00).
      CONCLUSIONS: The isotopic source signatures presented in this emission inventory
      can be used as an additional tool in identifying NH3 emission sources and tracing
      their transport across localized landscapes and regions. The insight into the
      transport of NH3 emissions provided by isotopic investigation is an important
      step in devising strategies to reduce future NH3 emissions, a mounting concern
      for air quality scientists, epidemiologists, and policy-makers.

PMID- 24019190
TI  - De novo sequencing of short interfering ribonucleic acids facilitated by use of
      tandem mass spectrometry with ion mobility spectrometry.
AB  - RATIONALE: The use of RNAi for new therapeutics is becoming more widespread. To
      improve the development and quality control of such materials there is a need for
      rapid, accurate and meaningful analyses. Here, the use of negative ion nano
      electrospray ionisation tandem mass spectrometry with ion mobility spectrometry
      (nESI-MS/MS-IMS-MS) is shown to simplify data interpretation and lead to higher
      sequence coverage. METHODS: A set of 20-nucleotide RNA molecules was analysed
      using nESI-MS/MS and their sequences determined manually with the aid of the
      Simple Oligonucleotide Sequencer (SOS) program. The RNAs were also analysed using
      nESI-MS/MS-IMS-MS. This incorporates an extra step involving travelling-wave IMS
      separation of the product ions into groups according to the number of charges
      that the ions carry. Following this, the RNA sequences were determined from the
      separated groups of ions. RESULTS: nESI-MS/MS collision-induced dissociation of
      the RNA sequences produced w, y, a-(Base) and c product ions. Sequence
      determination resulted in incomplete coverage with bases in the centre of the
      sequences being unidentifiable because of the plethora of overlapping ions.
      Sequencing carried out from the nESI-MS/MS-IMS-MS data, whereby individual
      product ion spectra arising only from ions carrying the same charge were
      generated, gave full sequence coverage for each nucleotide (except y1 ) with
      assignment confirmation from a minimum of four different product ions.
      CONCLUSIONS: Using nESI-MS/MS-IMS-MS to analyse a number of 20-nucleotide RNA
      molecules produced full sequence coverage with 100% accuracy, in addition to
      molecular mass confirmation. This method has the potential for automation for
      higher sample throughput and thus constitutes a robust approach for the quality
      control of RNAs in therapeutics.

PMID- 24019191
TI  - Spatial variability in sulphur isotope values of archaeological and modern cod
      (Gadus morhua).
AB  - RATIONALE: This study presents the first sulphur isotope data of modern and
      archaeological cod (Gadus morhua) bone collagen, undertaken to identify large
      scale spatial variability of significance as both baseline values for studies of
      human diet and a potential variable in isotope-based studies of fish trading.
      METHODS: Collagen was extracted from modern and archaeological cod bones using a
      weak HCl solution and analysed for its sulphur isotopic composition by isotope
      ratio mass spectrometry (IRMS). RESULTS: The archaeological cod have sulphur
      isotope values ranging from +9.10/00 to +18.20/00, whereas values for modern
      specimens range from +14.80/00 to +18.30/00. The modern data show values implying
      less freshwater influence, consistent with their offshore catch locations, but
      also corroborate some of the regional variability evident from the archaeological
      evidence. CONCLUSIONS: The archaeological data have a large range of sulphur
      isotope values compared with the modern populations, probably indicating they
      were taken from a wide range of geographic locations, including both coastal and
      offshore locales. They show broad trends of regional difference that may relate
      to both the fish populations targeted (e.g. 'inshore' versus 'offshore') and the
      baseline values of the local ecosystem (e.g. degree of freshwater input from
      river systems).

PMID- 24019192
TI  - Ion mobility and liquid chromatography/mass spectrometry strategies for exhaled
      breath condensate glucose quantitation in cystic fibrosis studies.
AB  - RATIONALE: Cystic fibrosis related diabetes (CFRD) is an important complication
      of cystic fibrosis (CF) because it causes acceleration in the decline in lung
      function. Monitoring concentrations of key metabolites such as glucose in airway
      lining fluid is necessary for improving our understanding of the biochemical
      mechanisms linking diabetes and CF. Targeted-metabolomic strategies for glucose
      quantitation in exhaled breath condensate (EBC) from healthy individuals are
      presented. METHODS: Three different electrospray ionization mass spectrometry
      (ESI-MS)-based methods were developed for EBC sample interrogation and glucose
      quantitation without derivatization. Two methods utilized ultra-high-performance
      liquid chromatography (UHPLC) coupled to either time-of-flight (TOF) MS or triple
      quadrupole (QqQ) tandem MS (MS/MS). A third approach involved direct-infusion
      traveling wave ion mobility spectrometry (TWIMS) with TOF-MS detection. UHPLC/QqQ
      MS/MS was used for urea quantitation as the EBC dilution marker. Matrix effects
      were mitigated using isotopically labeled glucose and urea as internal standards.
      RESULTS: All the developed methods allowed glucose and urea quantitation in EBC
      with high accuracy and precision. The UHPLC/TOF-MS and UHPLC/QqQ-MS/MS methods
      provided similar analytical figures of merit. UHPLC/QqQ-MS/MS provided the
      highest sensitivity and the lowest limit of detection (LOD) of 1.5 nM in EBC for
      both glucose and urea. The TWIMS-TOF-MS-based method provided the highest sample
      throughput capability; however, the glucose LOD was ~3-fold higher than with the
      two chromatographic methods. CONCLUSIONS: Mass spectrometric methods for the
      quantitative analysis of trace EBC glucose levels are reported and compared for
      the first time. The analytical figures of merit demonstrate the applicability of
      these methods to metabolite analysis of airway samples for CF and CFRD research.

PMID- 24019193
TI  - Fragmentation pathways of 2-substituted pyrrole derivatives using electrospray
      ionization ion trap and electrospray ionization quadrupole time-of-flight mass
      spectrometry.
AB  - RATIONALE: Pyrrole derivatives are of considerable importance and are present in
      a wide range of natural products and used extensively in drug discovery.
      Fragmentation pathway studies play an important role in the structural
      identification of pyrrole derivatives. As a part of our ongoing work on
      heterocycles, fragmentation pathways of 2-substituted pyrrole derivatives were
      investigated by mass spectrometry (MS). METHODS: Twelve pyrrole derivatives were
      synthesized and analyzed. Low-resolution fragmentation ions of all the compounds
      were generated by ion trap mass spectrometry (ITMS(n) ) with an electrospray
      ionization (ESI) source in positive mode. Hybrid quadrupole time-of-flight mass
      spectrometry (QTOFMS) was used to determine the elemental compositions of the
      resultant product ions. RESULTS: The side-chain substituents at the 2-position
      influence the fragmentation pathways. Typical losses of H2 O, aldehydes and
      pyrrole moieties from the [M + H](+) ion are observed for the compounds with side
      chains bearing aromatic groups at the 2-position of the pyrrole. However, losses
      of H2 O, alcohols and C3 H6 are the main cleavage pathways for compounds 6 and 12
      with nonphenyl-substituted side chains at the 2-position. CONCLUSIONS: Typical
      fragmentation mechanisms of 2-substituted pyrrole derivatives are proposed and
      elucidated based on the observations of ITMS(n) and QTOFMS spectra. The results
      showed that the fragmentation pathways were remarkably influenced by the side
      chain substituents at the 2-position of pyrrole. This investigation should have
      value in the structural identification of this series of molecules or compounds
      with similar structures.

PMID- 24019194
TI  - Characterisation of 3-aminoquinoline-derivatised isomeric oligogalacturonic acid
      by travelling-wave ion mobility mass spectrometry.
AB  - RATIONALE: Mass spectrometry has become a useful technique for elucidating the
      chemical structures of oligosaccharides. The combined use of chromatography and
      mass spectrometry for the separation and identification of oligosaccharides has
      shown much progress in recent years. However, no powerful method has yet been
      developed to quickly identify isomeric oligosaccharides in complex mixtures.
      METHODS: A rapid travelling-wave ion mobility mass spectrometry (TWIMS-MS) method
      was developed for the identification of various isomeric oligogalacturonic acids
      in mixtures and determined their structures, using 3-aminoquinoline (3-AQ) as a
      labelling agent. RESULTS: TWIMS successfully distinguished isomeric
      oligogalacturonic acids of various degrees of polymerisation (DPs) and levels of
      methyl-esterification. After derivatisation by 3-AQ, isomeric oligosaccharides of
      galacturonic acid, with the DP ranging from 2 to 9 and the number of methyl
      esters ranging from 1 to 5, were identified by 3-AQ-TWIMS-MS. The isomeric
      oligosaccharides with varying sites of methyl ester substitution were identified
      by the post-fragmentation mode of TWIMS using 3-AQ labelling to obtain simplified
      mass spectra. CONCLUSIONS: Using the 3-AQ-TWIMS-MS method, the precise
      distribution of methyl esters within the pectin molecule and isomeric
      oligogalacturonic acids after enzyme degradation was determined. Simplified
      product ion mass spectra and precise analysis of the isomers were achieved by
      labelling 3-AQ at the reducing end of the oligosaccharides. Series of methyl
      esterified galacturonic acid oligomers have predictable drift times, depending on
      the precise position of the methyl ester.

PMID- 24019195
TI  - Use of prescription antiobesity drugs in the United States.
AB  - STUDY OBJECTIVE: To examine national trends in prescription antiobesity drug use
      in the United States. DESIGN: Data analysis. DATA SOURCE: The IMS Health Vector
      One National and Total Patient Tracker and Encuity Research Treatment Answers
      databases, the Source Healthcare Analytics Source Lx database, and IMS LifeLink
      database. MEASUREMENTS AND MAIN RESULTS: National drug use estimates from 1991
      2011 were extracted from the IMS Health Vector One National database, and patient
      characteristics from 2008-2011 were extracted from the Vector One Total Patient
      Tracker and Encuity Research Treatment Answers databases. The Source Healthcare
      Analytics Source Lx database was used to examine duration of antiobesity drug use
      from 2002-2011, with a sensitivity analysis performed using the IMS LifeLink
      database. In 2011, approximately 2.74 million patients used antiobesity drugs,
      predominantly phentermine (2.43 million patients). The use of prescription
      orlistat and sibutramine was relatively uncommon. Eighty-five percent of
      antiobesity drug users were female, 62% were aged 17-44 years, and 4.5% had a
      body mass index of <= 24.9 kg/m(2) . Duration of use was generally short and most
      patients only had one episode of antiobesity drug use during the observation
      period. The longest episode of use was 30 days or less in 47-58% of patients.
      Approximately one quarter of the patients used antiobesity drugs for longer than
      90 days, including phentermine and other amphetamine congeners whose labels
      recommend short-term use, not exceeding "a few weeks." Only 1.3-4.2% of
      antiobesity drug users used them for longer than 1 year. Concomitant use of two
      or more prescription weight-loss drugs was generally uncommon, although
      phentermine was dispensed during 13-16% of benzphetamine, diethylpropion, or
      phendimetrazine episodes of use. CONCLUSION: Phentermine dominated the
      prescription weight-loss market. Despite the indication of short-term use for
      amphetamine congeners, duration of use was similar to other antiobesity drugs.
      Nevertheless, the reasons for and implications of the limited duration of use
      observed with all prescription antiobesity drugs deserve further investigation.

PMID- 24019197
TI  - Bronchodilation with mometasone furoate/formoterol fumarate administered by
      metered-dose inhaler with and without a spacer in children with persistent
      asthma.
AB  - BACKGROUND: The bronchodilatory effect of mometasone furoate/formoterol fumarate
      (MF/F) administered by metered-dose inhaler (MDI) with or without a spacer has
      not been evaluated previously in children aged 5-11 years. METHODS: This was a
      randomized, multicenter, placebo-controlled, single-dose, four-period crossover
      study. Children with persistent asthma aged 5-11 years participated in this
      study. Subjects used inhaled corticosteroids with/without long-acting beta-2
      agonists for 12 weeks before enrollment and at screening had forced expiratory
      volume in 1 sec (FEV1 ) >=70% predicted. Subjects received MF/F MDI 100/10 ug
      with/without spacer (AeroChamber Plus(r) with Flow-Vu(r) Anti-Static Valved
      Holding Chamber), F-Dry Powder Inhaler (F-DPI) 10 ug, and placebo MDI
      with/without spacer in separate treatment periods. The primary endpoint was FEV1
      area under the curve from 0 to 12 hr (AUC0-12hr ) for the comparison of MF/F with
      spacer versus placebo. Secondary measurements included MF/F without spacer versus
      placebo, as well as MF/F with spacer versus MF/F without spacer, and F-DPI versus
      placebo. Analysis was performed with an analysis of covariance model for a
      crossover study. RESULTS: Data from 87 subjects were analyzed. MF/F with spacer
      demonstrated a larger change in mean FEV1 AUC0-12hr versus placebo (115 vs. -9
      mL), with a treatment difference of 124 mL (95% CI 94-154, P < 0.001). Similarly,
      MF/F without spacer versus placebo resulted in a 102 mL difference in mean
      adjusted FEV1 AUC0-12hr (95% CI 73-131, P < 0.001), whereas the difference
      between MF/F with spacer versus MF/F without spacer was 22 mL (95% CI -8 to 52, P
      = 0.144). The difference between F-DPI versus placebo was 106 mL (95% CI 77-135,
      P < 0.001). No unexpected adverse events were observed. CONCLUSIONS: In this
      trial, MF/F MDI 100/10 ug demonstrated significant bronchodilation in children
      aged 5-11 years regardless of the use of a spacer. No difference in
      bronchodilation was observed between MF/F MDI and F-DPI.

PMID- 24019198
TI  - Crystal structure evolution of individual graphene islands during CVD growth on
      copper foil.
AB  - Single-crystal percentage of graphene islands on Cu foil is associated with
      island sizes and shapes. In polycrystalline islands, certain grain boundary types
      are favored. There is no obvious relation between the number of lobes and grain
      orientations. An observed structure evolution and surface disorder of Cu grains
      can be possible factors for the formation of grain boundaries within graphene
      islands. 

PMID- 24019196
TI  - Spiritual quality of life in advanced cancer patients receiving radiation
      therapy.
AB  - OBJECTIVE: The aim of this randomized controlled trial for patients with advanced
      cancer receiving radiation therapy was to determine the effect of a
      multidisciplinary intervention on spiritual quality of life (QOL) at the end of
      the intervention (week 4) and at two follow-up time points (weeks 26 and 52).
      METHODS: One hundred thirty-one persons were randomized to either the
      intervention or control (forms only) groups. The intervention included six 90-min
      in-person sessions based on the physical, emotion, social, and spiritual domains
      of QOL. Three sessions included the spiritual component. Caregivers were present
      for four sessions, one which included a spiritual component. Ten follow-up phone
      calls were made to the patients in the intervention group during the 6-month
      follow-up period. Patients completed the Functional Assessment of Cancer Therapy:
      General Scale, the Linear Analog Self-Assessment which includes an assessment of
      spiritual QOL, and the Functional Assessment of Chronic Illness Therapy-Spiritual
      Well-Being (FACIT-Sp) at enrollment, and weeks 4, 27, and 52. RESULTS: Following
      the intervention, the intervention group demonstrated improved spiritual QOL on
      the FACIT-Sp, whereas the spiritual QOL of the control group decreased, resulting
      in significant mean changes between groups (total score: 1.7 vs. -2.9; p < 0.01;
      meaning/peace subscale: 1.0 vs. -3.5; p < 0.01; faith subscale: 3.1 vs. -1.7; p =
      0.04). CONCLUSIONS: The results indicate that a multidisciplinary intervention
      which includes a spiritual component can maintain the spiritual QOL of patients
      with advanced cancer during radiation therapy.

PMID- 24019199
TI  - Comparison of loading rate-dependent injury modes in a murine model of post
      traumatic osteoarthritis.
AB  - Post-traumatic osteoarthritis (PTOA) is a common long-term consequence of joint
      injuries such as anterior cruciate ligament (ACL) rupture. In this study we used
      a tibial compression overload mouse model to compare knee injury induced at low
      speed (1 mm/s), which creates an avulsion fracture, to injury induced at high
      speed (500 mm/s), which induces midsubstance tear of the ACL. Mice were
      sacrificed at 0 days, 10 days, 12 weeks, or 16 weeks post-injury, and joints were
      analyzed with micro-computed tomography, whole joint histology, and biomechanical
      laxity testing. Knee injury with both injury modes caused considerable trabecular
      bone loss by 10 days post-injury, with the Low Speed Injury group (avulsion)
      exhibiting a greater amount of bone loss than the High Speed Injury group
      (midsubstance tear). Immediately after injury, both injury modes resulted in
      greater than twofold increases in total AP joint laxity relative to control
      knees. By 12 and 16 weeks post-injury, total AP laxity was restored to uninjured
      control values, possibly due to knee stabilization via osteophyte formation. This
      model presents an opportunity to explore fundamental questions regarding the role
      of bone turnover in PTOA, and the findings of this study support a biomechanical
      mechanism of osteophyte formation following injury.

PMID- 24019200
TI  - Redesigning space for interdisciplinary connections: the Puget Sound Science
      Center.
AB  - Mindful design of learning spaces can provide an avenue for supporting student
      engagement in STEM subjects. Thoughtful planning and wide participation in the
      design process were key in shaping new and renovated spaces for the STEM
      community at the University of Puget Sound. The finished project incorporated
      Puget Sound's mission and goals as well as attention to pedagogical principles,
      and led to connections and integration throughout the learning environment,
      specifically at the biochemistry and molecular life sciences intersections.

PMID- 24019202
TI  - Using multiple imputation to estimate cumulative distribution functions in
      longitudinal data analysis with data missing at random.
AB  - In longitudinal clinical studies, after randomization at baseline, subjects are
      followed for a period of time for development of symptoms. The interested
      inference could be the mean change from baseline to a particular visit in some
      lab values, the proportion of responders to some threshold category at a
      particular visit post baseline, or the time to some important event. However, in
      some applications, the interest may be in estimating the cumulative distribution
      function (CDF) at a fixed time point post baseline. When the data are fully
      observed, the CDF can be estimated by the empirical CDF. When patients
      discontinue prematurely during the course of the study, the empirical CDF cannot
      be directly used. In this paper, we use multiple imputation as a way to estimate
      the CDF in longitudinal studies when data are missing at random. The validity of
      the method is assessed on the basis of the bias and the Kolmogorov-Smirnov
      distance. The results suggest that multiple imputation yields less bias and less
      variability than the often used last observation carried forward method.

PMID- 24019201
TI  - CD161++ CD8+ T cells, including the MAIT cell subset, are specifically activated
      by IL-12+IL-18 in a TCR-independent manner.
AB  - CD161(++) CD8(+) T cells represent a novel subset that is dominated in adult
      peripheral blood by mucosal-associated invariant T (MAIT) cells, as defined by
      the expression of a variable-alpha chain 7.2 (Valpha7.2)-Jalpha33 TCR, and IL
      18Ralpha. Stimulation with IL-18+IL-12 is known to induce IFN-gamma by both NK
      cells and, to a more limited extent, T cells. Here, we show the CD161(++) CD8(+)
      T-cell population is the primary T-cell population triggered by this mechanism.
      Both CD161(++) Valpha7.2(+) and CD161(++) Valpha7.2(-) T-cell subsets responded
      to IL-12+IL-18 stimulation, demonstrating this response was not restricted to the
      MAIT cells, but to the CD161(++) phenotype. Bacteria and TLR agonists also
      indirectly triggered IFN-gamma expression via IL-12 and IL-18. These data show
      that CD161(++) T cells are the predominant T-cell population that responds
      directly to IL-12+IL-18 stimulation. Furthermore, our findings broaden the
      potential role of MAIT cells beyond bacterial responsiveness to potentially
      include viral infections and other inflammatory stimuli. 

PMID- 24019203
TI  - A pragmatic dose-finding approach using short-term surrogate efficacy outcomes to
      evaluate binary efficacy and toxicity outcomes in phase I cancer clinical trials.
AB  - There is a growing need for study designs that can evaluate efficacy and toxicity
      outcomes simultaneously in phase I or phase I/II cancer clinical trials. Many
      dose-finding approaches have been proposed; however, most of these approaches
      assume binary efficacy and toxicity outcomes, such as dose-limiting toxicity
      (DLT), and objective responses. DLTs are often defined for short time periods. In
      contrast, objective responses are often defined for longer periods because of
      practical limitations on confirmation and the criteria used to define
      'confirmation'. This means that studies have to be carried out for unacceptably
      long periods of time. Previous studies have not proposed a satisfactory solution
      to this specific problem. Furthermore, this problem may be a barrier for
      practitioners who want to implement notable previous dose-finding approaches. To
      cope with this problem, we propose an approach using unconfirmed early responses
      as the surrogate efficacy outcome for the confirmed outcome. Because it is
      reasonable to expect moderate positive correlation between the two outcomes and
      the method replaces the surrogate outcome with the confirmed outcome once it
      becomes available, the proposed approach can reduce irrelevant dose selection and
      accumulation of bias. Moreover, it is also expected that it can significantly
      shorten study duration. Using simulation studies, we demonstrate the positive
      utility of the proposed approach and provide three variations of it, all of which
      can be easily implemented with modified likelihood functions and outcome variable
      definitions.

PMID- 24019205
TI  - Vancomycin dosing in children and young adults: back to the drawing board.
AB  - STUDY OBJECTIVE: To compare the likelihood of alternative vancomycin dosing
      strategies based on weight, height, or body surface area (BSA) in achieving
      isometric vancomycin area under the serum concentration-time curve (AUC) values
      across the body size distribution of children and young adults. DESIGN: Maximum a
      posteriori probability Bayesian (MAP-Bayesian) pharmacokinetic analysis using
      retrospectively collected medical record data. SETTING: Children's hospital.
      PATIENTS: A total of 115 patients 1-20 years of age managed outside of the
      intensive care unit who were treated with vancomycin between May 1, 2011, and
      August 31, 2012, and had a minimum of two serum vancomycin concentration
      measurements. MEASUREMENTS AND MAIN RESULTS: Vancomycin dosing and concentration
      time information along with demographic and laboratory data related to kidney
      function estimation were extracted from the patients' medical records. A
      previously structured one-compartment model was used to derive MAP-Bayesian
      estimates of pharmacokinetic system parameters for each patient. Post hoc linear
      and power function regression were used to compare clearance (Cl) and the volume
      of distribution of the central compartment (Vc) to body size descriptors (weight,
      height, and BSA). The relationship of the body size descriptor-indexed parameter
      across the body size distribution was assessed. The AUC from time 0 to 24 hours
      (AUC24 ) values associated with vancomycin dosing regimens based on weight,
      height, and BSA were estimated. The 115 patients (56.5% male) had a mean +/- SD
      age, height, and weight of 9.7 +/- 5.4 years, 133 +/- 32.3 cm, and 38.0 +/- 24.2
      kg, respectively. Each patient received a minimum of four doses of vancomycin and
      had two to nine serum vancomycin concentration measurements, for a total of 313
      measurements for all patients. Vancomycin Cl was a nonlinear function of weight
      and a linear-proportionate function of BSA, whereas the volume of distribution of
      the central compartment (Vc) was a linear-proportionate function of weight. The
      expected median (5th-95th percentile) AUC24 values with weight-based dosing of
      vancomycin 60-70 mg/kg/day were 446 (315-834) mg.hour/L and 649 (385-1165)
      mg.hour/L in patients weighing less than 40 kg (n=72) and those weighing 40 kg or
      more (n=43), respectively. In contrast, isometric AUC24 values were predicted
      with BSA-based dosing across the body size distribution. CONCLUSION: BSA-based
      dosing is more likely than weight-based (mg/kg) dosing of vancomycin to achieve
      isometric AUC24 values across the body size distribution of children and young
      adults. Pharmacokinetic studies that compare these two vancomycin dosing
      strategies in children are clearly needed to validate these findings.

PMID- 24019206
TI  - Taking three-dimensional two-photon excitation microscopy further: encoding the
      light for decoding the brain.

PMID- 24019207
TI  - Lactobacillus acidophilus La5, Bifidobacterium BB12, and Lactobacillus casei
      DN001 modulate gene expression of subset specific transcription factors and
      cytokines in peripheral blood mononuclear cells of obese and overweight people.
AB  - Probiotics are believed to have interaction with immune cells through sustained
      effects on gene expression of different cytokines and transcription factors. The
      present randomized doubled-blind controlled clinical trial was performed
      recruiting 75 individuals with BMI 25-35, who were randomly assigned to the
      following three groups: Group 1 (n = 25) who consumed regular yogurt as part of a
      low calorie diet [RLCD], group 2 (n = 25) who received probiotic yogurt with a
      LCD [PLCD] and group 3 (n = 25) who consumed probiotic yogurt without LCD [PWLCD]
      for 8 week. Participants in PLCD and PWLCD groups received 200 g/day yogurt
      containing Lactobacillus acidophilus La5, Bifidobacterium Bb12, and lactobacillus
      casei DN001 10(8) cfu/gr. The expression of the FOXP3, T-bet, GATA3, TNF-alpha,
      IFN-gamma, TGF-beta, and ROR-gammat in PBMCs genes were assessed, before and
      after intervention. In three groups, ROR-gammat expression was reduced (P =
      0.007) and FOXP3 was increased (P < 0.001). The expression of TNFalpha, TGFbeta,
      and GATA3 genes did not change among all groups after intervention.
      Interestingly, the expression of T-bet gene, which was significantly decreased in
      PLCD and PWLCD groups (P < 0.001), whereas gene expression of IFN-gamma decreased
      in all three groups. Our results suggest that weight loss diet and probiotic
      yogurt had synergistic effects on T-cell subset specific gene expression in
      peripheral blood mononuclear cells among overweight and obese individuals.

PMID- 24019210
TI  - Content validity of the National Board Dental Hygiene Examination.
AB  - This article describes a protocol that was employed to validate the content of
      the National Board Dental Hygiene Examination (NBDHE) using two separate practice
      analyses. The protocol consisted of the following phases: (1) the careful
      definition of the domain of knowledge and skills required for successful entry
      level dental hygiene practice, (2) the conduct of a survey to gather information
      regarding the judgments of practicing dental hygienists on the important
      knowledge, abilities, and skills required of entry-level dental hygiene practice,
      (3) the analysis of the survey data, (4) the integration of the survey findings
      with the examination content using a two-dimensional matrix, (5) development of
      the updated specifications of the examination based on the practice analysis
      data, and (6) implementation of the updated specifications for subsequent item
      and test development. Survey data from 1,284 and 1,388 full-time practicing
      dental hygienists for the 2002 and 2009 practice analyses, respectively, were
      analyzed. A two-dimensional matrix was used to map the content of the examination
      to the practice of dental hygiene based on the practice analysis data. The
      mapping showed that the distribution of items in the content specifications
      reflected actual dental hygiene practice. Thus, the adequacy of the content
      validity of the NBDHE was confirmed.

PMID- 24019209
TI  - Identifying emerging research collaborations and networks: method development.
AB  - Clinical and translational research is a multidisciplinary, collaborative team
      process. To evaluate this process, we developed a method to document emerging
      research networks and collaborations in our medical center to describe their
      productivity and viability over time. Using an e-mail survey, sent to 1,620
      clinical and basic science full- and part-time faculty members, respondents
      identified their research collaborators. Initial analyses, using Pajek software,
      assessed the feasibility of using social network analysis (SNA) methods with
      these data. Nearly 400 respondents identified 1,594 collaborators across 28
      medical center departments resulting in 309 networks with 5 or more
      collaborators. This low-burden approach yielded a rich data set useful for
      evaluation using SNA to: (a) assess networks at several levels of the
      organization, including intrapersonal (individuals), interpersonal (social),
      organizational/institutional leadership (tenure and promotion), and
      physical/environmental (spatial proximity) and (b) link with other data to assess
      the evolution of these networks.

PMID- 24019208
TI  - A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in
      vitro and in vivo.
AB  - Using a high-throughput screening (HTS) approach, we have identified and
      validated several small-molecule Mcl-1 inhibitors (SMI). Here, we describe a
      novel selective Mcl-1 SMI inhibitor, 2 (UMI-77), developed by structure-based
      chemical modifications of the lead compound 1 (UMI-59). We have characterized the
      binding of UMI-77 to Mcl-1 by using complementary biochemical, biophysical, and
      computational methods and determined its antitumor activity against a panel of
      pancreatic cancer cells and an in vivo xenograft model. UMI-77 binds to the BH3
      binding groove of Mcl-1 with Ki of 490 nmol/L, showing selectivity over other
      members of the antiapoptotic Bcl-2 family. UMI-77 inhibits cell growth and
      induces apoptosis in pancreatic cancer cells in a time- and dose-dependent
      manner, accompanied by cytochrome c release and caspase-3 activation.
      Coimmunoprecipitation experiments revealed that UMI-77 blocks the
      heterodimerization of Mcl-1/Bax and Mcl-1/Bak in cells, thus antagonizing the Mcl
      1 function. The Bax/Bak-dependent induction of apoptosis was further confirmed
      using murine embryonic fibroblasts that are Bax- and Bak-deficient. In an in vivo
      BxPC-3 xenograft model, UMI-77 effectively inhibited tumor growth. Western blot
      analysis in tumor remnants revealed enhancement of proapoptotic markers and
      significant decrease of survivin. Collectively, these promising findings show the
      therapeutic potential of Mcl-1 inhibitors against pancreatic cancer and warrant
      further preclinical investigations.

PMID- 24019211
TI  - Clinical use of tobramycin inhalation solution (TOBI(r)) shows sustained
      improvement in FEV1 in cystic fibrosis.
AB  - OBJECTIVES: Tobramycin inhalation solution (TIS; TOBI(r)) has improved forced
      expiratory volume in 1 sec (FEV1 ) in cystic fibrosis (CF) trials. Using data
      from the Epidemiologic Study of CF (ESCF), we assessed the change in level and
      trend of FEV1 % predicted (pred) over a 2-year period associated with initiation
      of TIS during routine clinical practice. METHODS: Patients age 8-38 years and in
      ESCF for >=2 years before treatment with TIS as a chronic therapy were selected
      if they remained on therapy for 2 years, defined as being on TIS for at least 3
      months per year (C-TIS group). Comparator intervals age 8-38 years used TIS <10%
      of the time. For each interval, we estimated the level and trend (rate of
      decline) in FEV1 % pred before and after the index using a piecewise linear mixed
      effects model adjusted for potential confounders. RESULTS: During the 2-year pre
      index period the C-TIS group (n = 2,534) had a more rapid decline in FEV1 (-2.49%
      vs. -1.39% pred/year) and a lower FEV1 at index (62.6% vs. 74.7% pred) than the
      comparator group (N = 17,656 intervals). After starting chronic TIS, the FEV1
      trend line over the 2-year post-index period was higher, but the comparator
      group's FEV1 was essentially unchanged (difference 2.22, P < 0.001). Change in
      slope was not different between groups (0.06, P = 0.82). CONCLUSIONS: Initiating
      chronic TIS therapy in the routine clinical care of patients with CF was
      associated with improvement in FEV1 % pred but no change in rate of decline,
      which means that this benefit was sustained over the 2 years studied.

PMID- 24019212
TI  - The complication of gastro-enteric fistulisation in neutropenic enterocolitis
      secondary to aplastic anaemia.
AB  - We report the case of a 27-month-old male with an unusual complication of
      aplastic anaemia and neutropenic enterocolitis. He suffered persistent
      neutropaenic sepsis and clinical deterioration forced the strategy of matched
      sibling haematopoietic stem cell transplantation. With engraftment and clinical
      recovery post-transplant, enteral feeding was re-established. Despite continued
      improvement the child began to vomit faeculent stomach content. Barium swallow
      showed gastro-colic and gastro-enteric fistulisation with contrast passing
      directly from stomach into descending colon and directly into jejunum. Laparotomy
      confirmed complex fistulae between the gastric body, the splenic flexure of the
      colon and the jejunum. The diagnosis and management of abdominal pathology
      secondary to severe pancytopaenia is challenging. Often the patient does not
      manifest the usual signs of acute abdominal pathology, making the decision to
      operate and the timing of surgery difficult. Counfounding this is the danger of
      performing surgery in a pancytopaenic patient. Our case illustrates these
      challenges and reports the unanticipated finding of a complex gastro-colic
      fistula.

PMID- 24019213
TI  - Embryonic development of chicken (Gallus Gallus Domesticus) from 1st to 19th day
      ectodermal structures.
AB  - Birds occupy a prominent place in the Brazilian economy not only in the poultry
      industry but also as an animal model in many areas of scientific research. Thus
      the aim of this study was to provide a description of macro and microscopic
      aspects of the ectoderm-derived structures in chicken embryos / fetuses poultry
      (Gallus gallus domesticus) from 1st to 19th day of incubation. 40 fertilized
      eggs, from a strain of domestic chickens, with an incubation period of 2-19 days
      were subjected to macroscopic description, biometrics, light, and scanning
      microscopy. All changes observed during the development were described. The
      nervous system, skin and appendages and organs related to vision and hearing
      began to be identified, both macro and microscopically, from the second day of
      incubation. The vesicles from the primitive central nervous system-forebrain,
      midbrain, and hindbrain-were identified on the third day of incubation. On the
      sixth day of incubation, there was a clear vascularization of the skin. The optic
      vesicle was first observed fourth day of development and on the fifth day there
      was the beginning of the lens formation. Although embryonic development is
      influenced by animal line as well as external factors such as incubation
      temperature, this paper provides a chronological description for chicken (Gallus
      gallus domesticus) during its embryonic development.

PMID- 24019214
TI  - Proteopedia entry: ricin.

PMID- 24019215
TI  - High-resolution MRI encoding using radiofrequency phase gradients.
AB  - Although MRI offers highly diagnostic medical imagery, patient access to this
      modality worldwide is very limited when compared with X-ray or ultrasound. One
      reason for this is the expense and complexity of the equipment used to generate
      the switched magnetic fields necessary for MRI encoding. These field gradients
      are also responsible for intense acoustic noise and have the potential to induce
      nerve stimulation. We present results with a new MRI encoding principle which
      operates entirely without the use of conventional B0 field gradients. This new
      approach--'Transmit Array Spatial Encoding' (TRASE)--uses only the resonant
      radiofrequency (RF) field to produce Fourier spatial encoding equivalent to
      conventional MRI. k-space traversal (image encoding) is achieved by spin
      refocusing with phase gradient transmit fields in spin echo trains. A transmit
      coil array, driven by just a single transmitter channel, was constructed to
      produce four phase gradient fields, which allows the encoding of two orthogonal
      spatial axes. High-resolution two-dimensional-encoded in vivo MR images of hand
      and wrist were obtained at 0.2 T. TRASE exploits RF field phase gradients, and
      offers the possibility of very low-cost diagnostics and novel experiments
      exploiting unique capabilities, such as imaging without disturbance of the main
      B0 magnetic field. Lower field imaging (<1 T) and micro-imaging are favorable
      application domains as, in both cases, it is technically easier to achieve the
      short RF pulses desirable for long echo trains, and also to limit RF power
      deposition. As TRASE is simply an alternative mechanism (and technology) of
      moving through k space, there are many close analogies between it and
      conventional B0 -encoded techniques. TRASE is compatible with both B0 gradient
      encoding and parallel imaging, and so hybrid sequences containing all three
      spatial encoding approaches are possible.

PMID- 24019217
TI  - Biomechanical comparison of syndesmotic injury fixation methods using a cadaveric
      model.
AB  - BACKGROUND: There is growing interest in suture-button devices for syndesmosis
      injury, which are intended to offer less rigid fixation than screw fixation.
      METHODS: The fixation strength with 2 different suture-button devices, ZipTight
      and TightRope, were compared using 5 cadaveric leg pairs (n = 10). In an
      additional 5 pairs (n = 10), ZipTight was compared to 3.5 mm quadricortical screw
      fixation. Ankle motion was measured intact, then following simulated syndesmosis
      injury and fixation. Cyclic loads (peak 750 N, 7.5 Nm) were applied. Finally,
      external rotation to failure was measured and failure mode was documented.
      RESULTS: Range of motion increased after simulated injury and fixation with all
      devices (max 14.5 degrees). In all groups, diastasis remained below 1.0 mm intact
      and below 2.0 mm during cyclic loading. Compared to intact, under load to
      failure, diastasis with ZipTight devices increased by 4.7 +/- 1.3 mm and 7.6 +/-
      4.3 mm, with TightRope, 6.3 mm, and screw construct, 1.3 mm. ZipTight specimens
      rotated approximately 80 +/- 22 degrees before failure, TightRope, 67 +/- 13
      degrees, screw constructs, 76 +/- 27 degrees. Mean failure torque was between
      22.2 +/- 6.9 Nm and 28.1 +/- 12.7 Nm for ZipTight, compared to 32.9 +/- 8.0 Nm
      for TightRope (P = .07), and 30.1 +/- 9.6 Nm for screw constructs (P = .03). The
      majority of suture-button constructs failed by fibular fracture (ZipTight = 6,
      TightRope = 4), the remaining by device pull-through (ZipTight = 3, TightRope =
      1) and loosening (ZipTight = 1). Conversely, 3 of screw-fixed specimens failed by
      device failure, 2 from bone fracture. CONCLUSION: Suture-button devices provided
      torsional strength below that of screw fixation. However, all devices may provide
      failure torques well above 20 Nm, exceeding likely torques applied in casts
      during healing.(1,2,4) CLINICAL RELEVANCE: Suture-button devices appear to have
      provided adequate fixation strength for syndesmosis injuries.

PMID- 24019216
TI  - Application of NT-proBNP in ventilator weaning for preterm infants with RDS.
AB  - OBJECTIVE: To evaluate the value of N-terminal pro-B-type natriuretic peptide (NT
      proBNP) levels along with spontaneous breathing trial (SBT) in the prediction of
      ventilator weaning outcome among respiratory distress syndrome (RDS) preterm
      infants ready to wean. METHODS: NT-proBNP along with plasma albumin
      concentration, serum sodium, serum potassium, and hematocrit were measured
      immediately before SBT in preterm infants (<=32 weeks) mechanically ventilated
      due to RDS. Extubation was considered successful if infants remained extubated
      >48 hr. Either SBT failure or extubation failure was considered weaning failure.
      RESULTS: Sixty-three of 88 infants passed the SBT and were subsequently
      extubated. Of these, two (3.2%) cases rapidly developed laryngeal dyspnea
      imposing reintubation (excluded from analysis). Of the remaining 61 infants, 45
      (73.8%) cases had successful extubation, and 16 (26.2%) cases were reintubated.
      Infants who failed weaning had lower gestational age, birth weight, and plasma
      albumin concentrations, higher NT-proBNP, doses of surfactant, occurrence of
      ventilator-associated pneumonia, and occurrence of pulmonary arterial
      hypertension than those who did not. NT-proBNP was the only independent factor
      that could predict weaning failure (OR = 1.872; P = 0.044). The ROC-AUC for NT
      proBNP to predict weaning failure was 0.977 (95% CI 0.918-0.997; P < 0.001). The
      cut-off of NT-proBNP level 18,500 pg/ml to predict weaning failure had a positive
      likelihood ratio of 25.180. The addition of NT-proBNP to SBT in prediction of
      weaning failure significantly improved the net reclassification improvement (NRI
      = 0.224; P = 0.034). CONCLUSION: NT-proBNP is an independent factor that could
      predict weaning failure. Measurement of NT-proBNP prior to SBT may be helpful in
      promoting successful ventilator weaning along with SBT.

PMID- 24019218
TI  - Rapid determination of partition coefficients of pharmaceuticals by phase
      distribution and microchip capillary electrophoresis with contactless
      conductivity detection.
AB  - A simple microchip CE method integrated with contactless conductivity detection
      was developed for the direct determination of partition coefficients of selected
      pharmaceuticals after phase distribution equilibrium. The equilibrium of
      distribution between two phases for four pharmaceuticals was performed using a 1
      octanol/water system and 1-octanol/buffer system. During the concentration
      determination, several major factors affecting detection were investigated in
      detail for each pharmaceutical to optimize the detection sensitivity. In the
      optimal conditions, sufficient electrophoretic separation and sensitive detection
      for each target analyte can be achieved within 40 s. The two systems showed a pH
      dependent partition behavior. Moreover, the measured values showed excellent
      agreement with those obtained by the traditional shake-flask method with HPLC-UV
      detection and literature reports, respectively. The developed method can be
      successfully applied to measure partition coefficient values of pharmaceuticals
      and requires much shorter analytical time compared to traditional methods. 

PMID- 24019219
TI  - Teaching structure: student use of software tools for understanding
      macromolecular structure in an undergraduate biochemistry course.
AB  - Because understanding the structure of biological macromolecules is critical to
      understanding their function, students of biochemistry should become familiar not
      only with viewing, but also with generating and manipulating structural
      representations. We report a strategy from a one-semester undergraduate
      biochemistry course to integrate use of structural representation tools into both
      laboratory and homework activities. First, early in the course we introduce the
      use of readily available open-source software for visualizing protein structure,
      coincident with modules on amino acid and peptide bond properties. Second, we use
      these same software tools in lectures and incorporate images and other structure
      representations in homework tasks. Third, we require a capstone project in which
      teams of students examine a protein-nucleic acid complex and then use the
      software tools to illustrate for their classmates the salient features of the
      structure, relating how the structure helps explain biological function. To
      ensure engagement with a range of software and database features, we generated a
      detailed template file that can be used to explore any structure, and that guides
      students through specific applications of many of the software tools. In
      presentations, students demonstrate that they are successfully interpreting
      structural information, and using representations to illustrate particular points
      relevant to function. Thus, over the semester students integrate information
      about structural features of biological macromolecules into the larger discussion
      of the chemical basis of function. Together these assignments provide an
      accessible introduction to structural representation tools, allowing students to
      add these methods to their biochemical toolboxes early in their scientific
      development.

PMID- 24019220
TI  - Oxandrolone for the treatment of bone marrow failure in Fanconi anemia.
AB  - BACKGROUND: A majority of Fanconi anemia (FA) patients will experience bone
      marrow failure (BMF) and androgen therapy (most often oxymetholone) may be
      utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone
      is associated with toxicities making identification of other agents of interest.
      In this study we aimed to evaluate the toxicity profile and hematologic response
      in patients with FA who are treated with low-dose oxandrolone, a synthetic non
      fluorinated anabolic steroid, similar to oxymetholone, with known dosing
      thresholds for virilization. PROCEDURE: A single arm, Phase I/II study was
      designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic
      response was noted at 16 weeks, a single dose escalation was offered. Subjects
      were regularly assessed for toxicity, including determinations of virilization,
      behavioral changes, and liver and kidney function. At 32 weeks, those who
      demonstrated hematologic response were allowed to continue study treatment, and
      those without improvement were deemed non-responsive. RESULTS: Nine subjects
      completed the study and were followed for a median of 99 weeks (46-136 weeks).
      Three (33.3%) subjects developed mild sub-clinical virilization and continued
      treatment with a dose reduction. None (0%) had adverse behavioral changes. Two
      (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven
      (77.8%) subjects had a hematologic response. CONCLUSION: Oxandrolone appears to
      be well-tolerated, has limited toxicities at the administered doses in FA with
      patients, and may be an alternative androgen for the treatment of BMF in FA.

PMID- 24019221
TI  - Content of children's loss of control eating episodes assessed by self-report and
      laboratory test meal.
AB  - Pediatric loss of control (LOC) eating heightens risk for excessive weight gain
      and further disordered eating. Assessment of LOC typically involves self-report
      interview or laboratory test meal, although no study has concurrently examined
      data from both methods. We gathered eating episode data via interview (Child
      Eating Disorder Examination; ChEDE) and a laboratory test meal, among 22
      overweight girls (aged 7-12 years) reporting LOC eating. Children consumed more
      energy during ChEDE episodes, although ChEDE and test meal episodes did not
      differ in macronutrient content. Episodes' correlation for amount consumed
      (grams) did not reach significance, p = .076. In exploratory analyses among the
      seven children reporting LOC during the test meal, episodes were significantly
      correlated for grams consumed. Findings provide preliminary data to suggest that
      semi-structured interviews accurately capture children's LOC episode quantity.
      Episodes did not qualitatively differ, although children reported consuming more
      energy during self-reported episodes. Replication is warranted in larger studies.

PMID- 24019222
TI  - Bioassays in natural product research - strategies and methods in the search for
      anti-inflammatory and antimicrobial activity.
AB  - INTRODUCTION: Identifying bioactive molecules from complex biomasses requires
      careful selection and execution of relevant bioassays in the various stages of
      the discovery process of potential leads and targets. OBJECTIVE: The aim of this
      review is to share our long-term experience in bioassay-guided isolation, and
      mechanistic studies, of bioactive compounds from different organisms in nature
      with emphasis on anti-inflammatory and antimicrobial activity. METHODS: In the
      search for anti-inflammatory activity, in vivo and in vitro model combinations
      with enzymes and cells involved in the inflammatory process have been used, such
      as cyclooxygenases, human neutrophils and human cancer cell lines. Methods
      concerning adsorption and perforation of bacteria, fungi, human cells and model
      membranes, have been developed and optimised, with emphasis on antimicrobial
      peptides and their interaction with the membrane target, in particular their
      ability to distinguish host from pathogen. RESULTS: A long-term research has
      provided experience of selection and combination of bioassay models, which has
      led to an increased understanding of ethnopharmacological and ecological
      observations, together with in-depth knowledge of mode of action of isolated
      compounds. CONCLUSION: A more multidisciplinary approach and a higher degree of
      fundamental research in development of bioassays are often necessary to identify
      and to fully understand the mode of action of bioactive molecules with novel
      structure-activity relationships from natural sources.

PMID- 24019223
TI  - Subtype-selective activation of K(v)7 channels by AaTXKbeta2-64, a novel toxin
      variant from the Androctonus australis scorpion venom.
AB  - K(v)7.4 channel subunits are expressed in central auditory pathways and in inner
      ear sensory hair cells and skeletal and smooth muscle cells. Openers of K(v)7.4
      channels have been suggested to improve hearing loss, systemic or pulmonary
      arterial hypertension, urinary incontinence, gastrointestinal and
      neuropsychiatric diseases, and skeletal muscle disorders. Scorpion venoms are a
      large source of peptides active on K+ channels. Therefore, we have optimized a
      combined purification/screening procedure to identify specific modulator(s) of
      K(v)7.4 channels from the venom of the North African scorpion Androctonus
      australis (Aa). We report the isolation and functional characterization of
      AaTXKbeta2-64, a novel variant of AaTXKbeta1-64, in a high-performance liquid
      chromatography fraction from Aa venom (named P8), which acts as the first peptide
      activator of K(v)7.4 channels. In particular, in both Xenopus oocytes and
      mammalian Chinese hamster ovary cells, AaTXKbeta2-64, but not AaTXKbeta1-64,
      hyperpolarized the threshold voltage of current activation and increased the
      maximal currents of heterologously expressed K(v)7.4 channels. AaTXKbeta2-64 also
      activated K(v)7.3, K(v)7.2/3, and K(v)7.5/3 channels, whereas homomeric K(v)1.1,
      K(v)7.1, and K(v)7.2 channels were unaffected. We anticipate that these results
      may prove useful in unraveling the novel biologic roles of AaTXKbeta2-64
      sensitive K(v)7 channels and developing novel pharmacologic tools that allow
      subtype-selective targeting of K(v)7 channels.

PMID- 24019225
TI  - A convenient and sensitive method for haloacetic acid analysis in tap water by on
      line field-amplified sample-stacking CE-ESI-MS.
AB  - In this study, we propose a simple strategy based on flow injection and field
      amplified sample-stacking CE-ESI-MS/MS to analyze haloacetic acids (HAAs) in tap
      water. Tap water was passed through a desalination cartridge before field
      amplified sample-stacking CE-ESI-MS/MS analysis to reduce sample salinity. With
      this treatment, the signals of the HAAs increased 300- to 1400-fold. The LODs for
      tap water analysis were in the range of 10 to 100 ng/L, except for the LOD of
      monochloroacetic acid (1 MUg/L in selected-ion monitoring mode detection). The
      proposed method is fast, convenient, and sensitive enough to perform on-line
      analysis of five HAAs in the tap water of Taipei City. Four HAAs, including
      trichloroacetic acid, dichloroacetic acid, dibromoacetic acid, and
      monobromoacetic acid, were detected at concentrations of approximately 1.74,
      1.15, 0.16, and 0.15 ppb, respectively. 

PMID- 24019224
TI  - Acetaminophen modulates P-glycoprotein functional expression at the blood-brain
      barrier by a constitutive androstane receptor-dependent mechanism.
AB  - Effective pharmacologic treatment of pain with opioids requires that these drugs
      attain efficacious concentrations in the central nervous system (CNS). A primary
      determinant of CNS drug permeation is P-glycoprotein (P-gp), an endogenous blood
      brain barrier (BBB) efflux transporter that is involved in brain-to-blood
      transport of opioid analgesics (i.e., morphine). Recently, the nuclear receptor
      constitutive androstane receptor (CAR) has been identified as a regulator of P-gp
      functional expression at the BBB. This is critical to pharmacotherapy of
      pain/inflammation, as patients are often administered acetaminophen (APAP), a CAR
      activating ligand, in conjunction with an opioid. Our objective was to
      investigate, in vivo, the role of CAR in regulation of P-gp at the BBB. Following
      APAP treatment, P-gp protein expression was increased up to 1.4-1.6-fold in a
      concentration-dependent manner. Additionally, APAP increased P-gp transport of
      BODIPY-verapamil in freshly isolated rat brain capillaries. This APAP-induced
      increase in P-gp expression and activity was attenuated in the presence of CAR
      pathway inhibitor okadaic acid or transcriptional inhibitor actinomycin D,
      suggesting P-gp regulation is CAR-dependent. Furthermore, morphine brain
      accumulation was enhanced by P-gp inhibitors in APAP-treated animals, suggesting
      P-gp-mediated transport. A warm-water (50 degrees C) tail-flick assay revealed a
      significant decrease in morphine analgesia in animals treated with morphine 3 or
      6 hours after APAP treatment, as compared with animals treated concurrently.
      Taken together, our data imply that inclusion of APAP in a pain treatment regimen
      activates CAR at the BBB and increases P-gp functional expression, a clinically
      significant drug-drug interaction that modulates opioid analgesic efficacy. 

PMID- 24019227
TI  - Jumping translocation in a case of de novo infant acute myeloid leukemia.
AB  - An infant presented with fever and purulent discharge from the left ear,
      proptosis of the right eye, and hepatosplenomegaly. She was diagnosed with acute
      monoblastic leukemia on morphological and flowcytometric analysis of the bone
      marrow. Karyotyping showed a jumping translocation (JT) involving the long arm of
      chromosome 1 as the sole cytogenetic abnormality in 29 metaphases. The patient
      died within 2 months of diagnosis. The presence of JT in a de novo infant AML as
      a sole cytogenetic abnormality indicates its possible role in leukemogenesis
      unlike previous reports that have implicated its role in tumor progression only.

PMID- 24019226
TI  - Vitamin D receptor (VDR) polymorphisms and severe RSV bronchiolitis: a systematic
      review and meta-analysis.
AB  - BACKGROUND: A number of small studies have suggested a relationship between
      vitamin D status and severe acute lower respiratory tract infection (ALRI),
      including RSV-bronchiolitis. The objective of this study was to evaluate the
      relationship between vitamin D receptor (VDR) polymorphism and severe RSV
      bronchiolitis through a systemic literature review and meta-analysis. METHODS: A
      comprehensive electronic literature search was conducted to identify all studies
      published before January 2013. Two reviewers independently screened all
      abstracts, followed by the full text of potential articles to evaluate
      eligibility. Study methodological quality was evaluated using the Newcastle
      Ottawa scale and individual component analysis. Meta-analysis evaluated
      associations at the allele and genotype levels. RESULTS: Of 803 studies
      identified from our literature search, three met eligibility criteria. Two VDR
      polymorphisms were included in more than one study: TaqI (rs731236) and FokI
      (rs2228570). All three reported a positive relationship between the FokI minor
      allele and disease with random effects meta-analyses demonstrating a
      statistically significant relationship (OR 1.52, CI: 1.12, 2.05). Genotype
      analysis was highly suggestive of a dominant or incomplete dominance model with
      combined odds ratios for fF (OR 1.73, CI: 0.92-3.36) and ff (OR 2.24, CI: 0.98
      5.14) compared to the FF genotype. No association between TaqI and severe RSV
      bronchiolitis was evident at the allele or genotype level. CONCLUSIONS: Available
      literature supports an association between the FokI polymorphism and severe RSV
      disease. Determination of VDR receptor polymorphism status could help predict
      high-risk infants who might benefit from preventive measures.

PMID- 24019228
TI  - Students' understanding of primary and secondary protein structure: drawing
      secondary protein structure reveals student understanding better than simple
      recognition of structures.
AB  - The interdisciplinary nature of biochemistry courses requires students to use
      both chemistry and biology knowledge to understand biochemical concepts. Research
      that has focused on external representations in biochemistry has uncovered
      student difficulties in comprehending and interpreting external representations
      in addition to a fragmented understanding of fundamental biochemistry concepts.
      This project focuses on students' understanding of primary and secondary protein
      structure and drawings (representations) of hydrogen-bonding in alpha helices and
      beta sheets. Analysis demonstrated that students can recognize and identify
      primary protein structure concepts when given a polypeptide. However, when asked
      to draw alpha helices and beta sheets and explain the role of hydrogen bonding
      their drawings students exhibited a fragmented understanding that lacked
      coherence. Faculty are encouraged to have students draw molecular level
      representations to make their mental models more explicit, complete, and
      coherent. This is in contrast to recognition and identification tasks, which do
      not adequately probe mental models and molecular level understanding.

PMID- 24019230
TI  - Triazole-containing hydrogels for time-dependent sustained drug release.
AB  - The purpose of this study is to develop novel triazole-containing hydrogels (TGs)
      as drug carrier and to investigate the sustained drug release accomplished by
      their time-dependent swelling behavior. The synthetic pathway of TGs includes:
      (1) DCC-coupling on hydroxyethyl methacrylate (HEMA) to prepare HEMA-alkyne (HA),
      (2) click-coupling to prepare a triazole-ring-containing monomer (TM), and (3)
      the synthesis of a series of TGs. The aggregation between triazole rings is found
      to be responsible for drug release controllability. Rhodamine 6G is studied as a
      model anticancer drug for release experiments. The effects of pH and temperature
      on the properties of sustained drug release are also studied. 

PMID- 24019229
TI  - Synthetic analogs of anoplin show improved antimicrobial activities.
AB  - We present the antimicrobial and hemolytic activities of the decapeptide anoplin
      and 19 analogs thereof tested against methicillin-resistant Staphylococcus aureus
      ATCC 33591 (MRSA), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC
      27853), vancomycin-resistant Enterococcus faecium (ATCC 700221) (VRE), and
      Candida albicans (ATCC 200955). The anoplin analogs contain substitutions in
      amino acid positions 2, 3, 5, 6, 8, 9, and 10. We use these peptides to study the
      effect of altering the charge and hydrophobicity of anoplin on activity against
      red blood cells and microorganisms. We find that increasing the charge and/or
      hydrophobicity improves antimicrobial activity and increases hemolytic activity.
      For each strain tested, we identify at least six anoplin analogs with an improved
      therapeutic index compared with anoplin, the only exception being Enterococcus
      faecium, against which only few compounds are more specific than anoplin. Both
      2Nal(6) and Cha(6) show improved therapeutic index against all strains tested.

PMID- 24019231
TI  - Aerobic fitness is associated with lower risk of hospitalization in children with
      cystic fibrosis.
AB  - BACKGROUND: Children with cystic fibrosis (CF) often have to be hospitalized
      because of acute exacerbation of their respiratory symptoms. Given the fact that
      improved peak oxygen uptake (VO2peak ) is positively associated with lung
      function and overall health in children with CF, this study examined the
      association between VO2peak and the need for hospitalization in a cohort of
      pediatric CF patients. METHODS: In a 3-year study, 77 CF children with mild-to
      moderately severe CF (forced expiratory volume in 1 sec [FEV1 ] >= 50%) underwent
      a maximal exercise test to determine VO2peak . Anthropometric, lung function and
      muscle strength measurements were also conducted and dates of hospitalization
      were recorded for the study period. Associations were then determined between the
      variables recorded and hospitalization by univariate and multivariate Cox
      proportional hazards regression analyses. RESULTS: VO2peak was 38.6 +/- 6.7 ml
      kg(-1)  min(-1) for boys and 31.9 +/- 6.9 ml kg(-1)  min(-1) for girls. In
      multivariate analyses, VO2peak was the only variable significantly associated
      with time to hospitalization (hazard ratio 0.91, P = 0.03). CONCLUSION: A
      significant association was detected between greater aerobic fitness, and lower
      risk of hospitalization. Because hospitalization due to respiratory exacerbation
      is a powerful prognostic factor, our findings provide further support for the
      importance of aerobic fitness evaluation in the management of children with mild
      to-moderately severe CF.

PMID- 24019232
TI  - Identification of annexin II as a novel secretory biomarker for breast cancer.
AB  - Early prediction of metastatic breast cancer is important for improvement of
      prognosis and survival rate. The present study aimed to identify secreted protein
      biomarkers for detection of invasive breast cancer. To this end, we performed a
      comparative proteomic analysis by a combination of 2DE and MALDI-TOF MS analysis
      of conditioned media from invasive H-Ras MCF10A human breast epithelial cells and
      noninvasive MCF10A and N-Ras MCF10A cells. We identified a list of 25 proteins
      that were strongly detected in media of H-Ras MCF10A and focused on annexin II,
      which was shown to be involved in cell motility. Invasive triple-negative human
      breast carcinoma cells, Hs578T, and MDA-MB-231, showed increased levels of
      annexin II in media, demonstrating that secretion of annexin II correlated well
      with the invasive phenotype of cells. We demonstrated a crucial role of annexin
      II in breast cell invasion/migration and actin cytoskeleton reorganization
      required for filopodia formation. Annexin II levels in the plasma samples and
      breast cancer tissues of breast cancer patients were significantly higher than
      those of normal groups, providing a clinical relevance to our in vitro findings.
      Taken together, we identified annexin II as a novel secretory biomarker candidate
      for invasive breast cancer, especially estrogen receptor-negative breast cancer. 

PMID- 24019233
TI  - Initial testing (Stage 1) of TAK-701, a humanized hepatocyte growth factor
      binding antibody, by the Pediatric Preclinical Testing Program.
AB  - TAK-701 is a humanized antibody that binds hepatocyte growth factor (HGF), thus
      suppressing c-Met transduced signaling and c-Met dependent proliferation and
      migration of tumor cells. Six childhood solid tumor xenografts were selected for
      evaluating TAK-701 based on immunochemical detection of HGF/c-Met autocrine
      signaling [i.e., pMet(Tyr1349) and HGF positive]. TAK-701 was tested using a dose
      of 30 mg/kg administered by the intraperitoneal (IP) route twice weekly for 4
      weeks. TAK-701 did not induce significant differences in EFS distribution in
      treated tumors compared to control tumors. Objective responses were not observed
      in any of the tested solid tumor xenografts.

PMID- 24019234
TI  - Foundational concepts and underlying theories for majors in "biochemistry and
      molecular biology".
AB  - Over the past two years, through an NSF RCN UBE grant, the ASBMB has held
      regional workshops for faculty members and science educators from around the
      country that focused on identifying: 1) core principles of biochemistry and
      molecular biology, 2) essential concepts and underlying theories from physics,
      chemistry, and mathematics, and 3) foundational skills that undergraduate majors
      in biochemistry and molecular biology must understand to complete their major
      coursework. Using information gained from these workshops, as well as from the
      ASBMB accreditation working group and the NSF Vision and Change report, the Core
      Concepts working group has developed a consensus list of learning outcomes and
      objectives based on five foundational concepts (evolution, matter and energy
      transformation, homeostasis, information flow, and macromolecular structure and
      function) that represent the expected conceptual knowledge base for undergraduate
      degrees in biochemistry and molecular biology. This consensus will aid
      biochemistry and molecular biology educators in the development of assessment
      tools for the new ASBMB recommended curriculum.

PMID- 24019235
TI  - Responsiveness of the Child Health Questionnaire-Parent Form in adolescents with
      non-specific chronic pain or fatigue.
AB  - BACKGROUND: The Child Health Questionnaire (CHQ) is a widely used instrument for
      measuring health-related quality of life covering both the physical and
      psychosocial domain. This study examined the responsiveness of the Dutch CHQ 50
      item Parent Form (PF50) in a sample of adolescents with chronic non-specific pain
      and/or fatigue. METHOD: Five different methods were used to calculate the
      responsiveness for the physical (PhS) and psychosocial (PsS) subscale of the CHQ
      50: standardized response mean (SRM), pooled effect sizes (ESs), standard error
      of measurement of agreement (SEMagreement ), minimal detectable change (MDC) and
      the area under the receiver operating characteristics (ROC) curve. For data
      analysis, the population was divided into two groups based on the parent's global
      perceived effect of treatment: a changed group (A) and an unchanged group (B).
      RESULTS: The responsiveness analyses were performed including 92 adolescents
      (88.0% girls; mean age 16.4 years). The SRMs are 2.89 and 1.01 for the PhS and
      PsS, respectively. Large ESs are found for group A (PhS = 3.30; PsS = 1.16). The
      method used for calculating SEMagreement results in a score of PhS = 18.92 and
      PsS = 11.39. The MDCs of PhS and PsS are 52.45 and 31.57, respectively. The area
      under the ROC curve (AUC) for PhS = 0.79 and for PsS = 0.64, and the
      corresponding optimal cut-off points are 21.1 and 7.0. CONCLUSION: Using the
      methods SRM, ES and AUC, the responsiveness of the CHQ-PF50 in adolescents with
      non-specific chronic pain or fatigue treated in a rehabilitation clinic is
      adequate for the physical scale and moderate for the psychosocial scale.

PMID- 24019236
TI  - Synchronized neonatal non-invasive ventilation-a pilot study: the graseby capsule
      with bi-level NCPAP.
AB  - OBJECTIVES: (1) To evaluate the Graseby capsule (GC) as a respiratory detection
      device when compared to respiratory inductance plethysmography (RIP); (2) to
      evaluate the response to the Graseby signal of a commercially available bi-level
      nasal CPAP device (BNCPAP) designed for use with the GC; and (3) to assess the
      performance of the GC/BNCPAP device when fitted on preterm infants. STUDY DESIGN:
      The study consisted of four parts: (1) The response characteristics of the
      GC/BNCPAP were assessed without connection to an infant; (2) the respiratory
      detection of both GC and RIP were compared in six preterm infants (mean 1,242 g,
      range 900-1,530 g); (3) the GC/BNCPAP was connected in six preterm infants (mean
      1,568 g, range 1,040-1,835 g), isolating the BNCPAP and the infant interaction by
      substituting an artificial "nose" for the infant and assessing performance using
      inspiratory times (Ti) of 0.1 through 0.5 sec with pressure levels of both 10/6
      and 8/5 cmH2 O; and (4) the GC/BNCPAP was employed as a respiratory support
      device in six preterm infants (mean 1,189 g, range 785-1,795 g) using clinically
      required pressures and evaluating performance using Ti of 0.3, 0.4 and 0.5 sec.
      RESULTS: (1) Within 26 ms of stimulation of the GC, the BNCPAP initiated air
      flow; however, the time to reach peak pressure was much longer; (2) the GC, when
      placed in the subxiphoid position, tracked the RIP signal nearly identically and
      occurred sooner; (3) a Ti of at least 0.3 sec was required to reach the desired
      high pressure setting; and (4) synchrony of the GC/BNCPAP occurred in 72-74% of
      infant breaths. CONCLUSIONS: The GC is a sensitive respiratory detection device;
      however, the GC/BNCPAP interface requires a minimum Ti of 0.3 sec and an adequate
      respiratory effort to achieve the desired pressure and to synchronously trigger
      the BNCPAP.

PMID- 24019237
TI  - Open parallel cooperative and competitive decision processes: a potential
      provenance for quantum probability decision models.
AB  - In recent years quantum probability models have been used to explain many aspects
      of human decision making, and as such quantum models have been considered a
      viable alternative to Bayesian models based on classical probability. One
      criticism that is often leveled at both kinds of models is that they lack a clear
      interpretation in terms of psychological mechanisms. In this paper we discuss the
      mechanistic underpinnings of a quantum walk model of human decision making and
      response time. The quantum walk model is compared to standard sequential sampling
      models, and the architectural assumptions of both are considered. In particular,
      we show that the quantum model has a natural interpretation in terms of a
      cognitive architecture that is both massively parallel and involves both co
      operative (excitatory) and competitive (inhibitory) interactions between units.
      Additionally, we introduce a family of models that includes aspects of the
      classical and quantum walk models. 

PMID- 24019238
TI  - On the biophysics and kinetics of toehold-mediated DNA strand displacement.
AB  - Dynamic DNA nanotechnology often uses toehold-mediated strand displacement for
      controlling reaction kinetics. Although the dependence of strand displacement
      kinetics on toehold length has been experimentally characterized and
      phenomenologically modeled, detailed biophysical understanding has remained
      elusive. Here, we study strand displacement at multiple levels of detail, using
      an intuitive model of a random walk on a 1D energy landscape, a secondary
      structure kinetics model with single base-pair steps and a coarse-grained
      molecular model that incorporates 3D geometric and steric effects. Further, we
      experimentally investigate the thermodynamics of three-way branch migration. Two
      factors explain the dependence of strand displacement kinetics on toehold length:
      (i) the physical process by which a single step of branch migration occurs is
      significantly slower than the fraying of a single base pair and (ii) initiating
      branch migration incurs a thermodynamic penalty, not captured by state-of-the-art
      nearest neighbor models of DNA, due to the additional overhang it engenders at
      the junction. Our findings are consistent with previously measured or inferred
      rates for hybridization, fraying and branch migration, and they provide a
      biophysical explanation of strand displacement kinetics. Our work paves the way
      for accurate modeling of strand displacement cascades, which would facilitate the
      simulation and construction of more complex molecular systems. 

PMID- 24019239
TI  - Transcriptional control by two interacting regulatory proteins: identification of
      the PtxS binding site at PtxR.
AB  - The PtxS and PtxR regulators control the expression of the glucose dehydrogenase
      genes from the Pgad promoter in Pseudomonas aeruginosa. These regulators bind to
      their cognate operators, that are separated by ~50 nt, within the promoter region
      and interact with each other creating a DNA-loop that prevents RNA polymerase
      promoter access. Binding of the 2-ketogluconate effector to PtxS caused PtxS/PtxR
      complex dissociation and led to the dissolution of the repression loop
      facilitating the entry of the RNA polymerase and enabling the transcription of
      the gad gene. We have identified a hydrophobic surface patch on the PtxR putative
      surface that was hypothesized to correspond to the binding site for PtxS. Two
      surface-exposed residues in this patch, V173 and W269, were replaced by alanine.
      Isothermal titration calorimetry assays showed that PtxS does not interact with
      the mutant variants of PtxR. Electrophoretic mobility shift assay and DNAase I
      footprinting assays proved that both regulators bind to their target operators
      and that failure to interact with each other prevented the formation of the DNA
      loop. In vitro transcription showed that PtxS per se is sufficient to inhibit
      transcription from the Pgad promoter, but that affinity of PtxS for its effector
      is modulated by PtxR. 

PMID- 24019240
TI  - Essential concepts and underlying theories from physics, chemistry, and
      mathematics for "biochemistry and molecular biology" majors.
AB  - Over the past two years, through an NSF RCN UBE grant, the ASBMB has held
      regional workshops for faculty members from around the country. The workshops
      have focused on developing lists of Core Principles or Foundational Concepts in
      Biochemistry and Molecular Biology, a list of foundational skills, and
      foundational concepts from Physics, Chemistry, and Mathematics that all
      Biochemistry or Molecular Biology majors must understand to complete their major
      coursework. The allied fields working group created a survey to validate
      foundational concepts from Physics, Chemistry, and Mathematics identified from
      participant feedback at various workshops. One-hundred twenty participants
      responded to the survey and 68% of the respondents answered yes to the question:
      "We have identified the following as the core concepts and underlying theories
      from Physics, Chemistry, and Mathematics that Biochemistry majors or Molecular
      Biology majors need to understand after they complete their major courses: 1)
      mechanical concepts from Physics, 2) energy and thermodynamic concepts from
      Physics, 3) critical concepts of structure from chemistry, 4) critical concepts
      of reactions from Chemistry, and 5) essential Mathematics. In your opinion, is
      the above list complete?" Respondents also delineated subcategories they felt
      should be included in these broad categories. From the results of the survey and
      this analysis the allied fields working group constructed a consensus list of
      allied fields concepts, which will help inform Biochemistry and Molecular Biology
      educators when considering the ASBMB recommended curriculum for Biochemistry or
      Molecular Biology majors and in the development of appropriate assessment tools
      to gauge student understanding of how these concepts relate to biochemistry and
      molecular biology.

PMID- 24019241
TI  - Proactive enteral tube feeding in pediatric patients undergoing chemotherapy.
AB  - BACKGROUND: To determine feasibility and safety of proactive enteral tube feeding
      (ETF) in pediatric oncology patients. METHODS: Pediatric patients with newly
      diagnosed brain tumors, myeloid leukemia or high-risk solid tumors were eligible.
      Subjects agreeing to start ETF before cycle 2 chemotherapy were considered
      proactive participants (PPs). Those who declined could enroll as chart collection
      receiving nutritional standard of care. Nutritional status was assessed using
      standard anthropometric measurements. Episodes of infection and toxicity related
      to ETF were documented from diagnosis to end of therapy. A descriptive comparison
      between PPs and controls was conducted. RESULTS: One hundred four eligible
      patients were identified; 69 enrolled (20 PPs and 49 controls). At diagnosis, 17%
      of all subjects were underweight and 26% overweight. Barriers to enrollment
      included physician, subject and/or family refusal, and inability to initiate ETF
      prior to cycle 2 of chemotherapy. Toxicity of ETF was minimal, but higher
      percentage of subjects in the proactive group had episodes of infection than
      controls. Thirty-nine percent of controls eventually started ETF and were twice
      as likely to receive parenteral nutrition. PPs experienced less weight loss at
      ETF initiation than controls receiving ETF and were the only group to demonstrate
      improved nutritional status at end of study. CONCLUSIONS: Proactive ETF is
      feasible in children with cancer and results in improved nutritional status at
      end of therapy. Episodes of infection in this study are concerning; therefore, a
      larger randomized trial is required to further delineate infectious risks and
      toxicities that may be mitigated by improved nutritional status.

PMID- 24019242
TI  - The long-term impact of tissue injury on pain processing and modulation: a study
      on ex-prisoners of war who underwent torture.
AB  - BACKGROUND: Tissue injury may, in some instances, induce chronic pain lasting for
      decades. Torture survivors suffer from high rates of chronic pain and
      hypersensitivity in the previously injured regions. Whether torture survivors
      display generalized alterations in pain perception and modulation, and whether
      such alterations underlie their chronic pain is unknown. We aimed at exploring
      the long-term alterations in pain perception and modulation in torture survivors.
      METHODS: In order to address these questions, a systematic quantitative
      somatosensory evaluation was performed in individuals (n = 60) who suffer from
      chronic pain, and who, decades previously, were tortured, resulting in
      substantial tissue damage. These individuals were compared with age- and sex
      matched individuals (n = 44) of similar background. Testing included the
      measurement of pain threshold and pain tolerance, perceived suprathreshold
      stimuli, conditioned pain modulation (CPM) and temporal summation of pain (TSP)
      in intact body regions. RESULTS: Chronic pain was found highly prevalent (86.6%)
      among torture survivors, who exhibited higher suprathreshold pain ratings (p <
      0.05), poorer CPM (p < 0.0001) and stronger TSP (p < 0.0001) than controls.
      Significant differences in CPM and TSP were also found between torture survivors
      and controls with chronic pain. Chronic pain intensity among torture survivors
      correlated negatively with the magnitude of CPM (r = -0.47, p < 0.01).
      CONCLUSIONS: Torture appears to induce generalized dysfunctional pain modulation
      that may underlie the intense chronic pain experienced by torture survivors
      decades after torture. The results may be generalized to instances where chronic
      pain exists for decades after severe injury in non-tortured populations and
      emphasize the importance of preventive care.

PMID- 24019243
TI  - Self-reported depression and anxiety symptoms in school-aged Singaporean
      children.
AB  - INTRODUCTION: Few studies have examined anxiety and depression experiences of
      primary (middle) school-aged children from ethnically diverse backgrounds, and
      most have relied on parents or others as informants. The present study aimed to
      investigate self-reported anxiety and depression symptoms in Singaporean primary
      school-aged children. Age, gender, and ethnic differences and interactions were
      explored as well as similarities and differences between Singaporean children and
      US norms. METHODS: A large representative community sample of 1655 8- to 12-year
      old Singaporean children (Chinese, Malay, and Indian) completed the
      Multidimensional Anxiety Scale for Children (MASC) and the Children's Depression
      Inventory (CDI) as part of a larger epidemiological study of mental health in
      Singaporean children. RESULTS: Rates of clinically elevated symptoms of anxiety
      and depression were 9.3% and 16.9% on the MASC and the CDI, respectively.
      Separation and social anxieties were most common. Evidence of a gender difference
      in levels of emotional symptoms was most evident in Indian children, with girls
      reporting more symptoms than boys. The relationship between age and internalizing
      problems was weak. DISCUSSION: A substantial minority of primary school-aged
      Singaporean children reported elevated anxious and depressive symptoms. Better
      understanding of the factors that contribute to the development and maintenance
      of these problems can help the development of culture-specific interventions and
      facilitate the planning of community-tailored services and initiatives.

PMID- 24019244
TI  - Diagnostic value of lung function parameters and FeNO for asthma in
      schoolchildren in large, real-life population.
AB  - BACKGROUND AND OBJECTIVE: To establish a diagnostic value of fractional exhaled
      nitric oxide (FeNO), interrupter resistance measurement (Rint), specific
      resistance of the airways (sRaw), spirometric parameters in asthma diagnosis in
      schoolchildren. METHODS: It was a retrospective, cross-sectional study. We
      evaluated data from medical documentation of 6,439 children (aged 6-18) with
      symptoms suggestive of asthma, who attended our Pediatric Allergic Outpatient
      Clinic. Medical documentation of the patients was analyzed with special attention
      to the first ever obtained results (before the introduction of controller
      medication) of: FeNO, Rint, sRaw, spirometry, diagnoses of allergic diseases, and
      allergen sensitization (specific IgE results). RESULTS: We included 3,612
      children in the analysis. Older age, male gender, the presence of allergic
      rhinitis, sensitization to perennial and seasonal allergens, higher FeNO and
      Rint, and FEV1 /FVC <80% were significantly associated with asthma. We observed a
      significant association between FeNO and Rint in the prediction of asthma
      diagnosis. Optimal cutoff points to differentiate asthmatics from non-asthmatics
      were established. Thus, Rint >175.4% was defined as asthma-predicting Rint, and
      FeNO >15.8 ppb was defined as asthma-predicting FeNO. In all study subgroups,
      sensitivity for asthma-predicting Rint was significantly higher than for asthma
      predicting FeNO with an inverse trend in specificity value. CONCLUSION: Our
      results suggest that asthma-predicting Rint and, to a lesser extent, asthma
      predicting FeNO, defined in the present study, could serve as a reliable tool to
      exclude asthma in schoolchildren. However, our results also indicate a clinically
      important fact that all lung function parameters or FeNO should be interpreted in
      the context of age, gender, allergy profile, and the presence of co-morbidities
      in schoolchildren. Pediatr Pulmonol. 2014; 49:632-640. (c) 2013 Wiley
      Periodicals, Inc.

PMID- 24019245
TI  - Suicidal risk, depression, and religiosity: a study of women in a general
      hospital in Santiago de Chile.
AB  - INTRODUCTION: The purpose of the present study is to compare the role of
      spiritual and religious beliefs in the prevention of suicidal risk among
      depressive women with suicidal ideation or attempts, treated in the psychiatric
      unit of a general hospital in Santiago de Chile (Servicio de Psiquiatria del
      Hospital del Salvador) between 2010 and 2011. METHOD: The relationship among
      severity of depression, suicidal risk, and religiosity is explored in women
      treated in Servicio de Psiquiatria del Hospital del Salvador. The
      sociodemographic and clinical characteristics of believers (n = 121) and
      nonbelievers (n = 22) were compared, and their global mental health was assessed,
      as well as their rating in scales for depression, anxiety, aggressivity, and
      impulsivity. RESULTS: Most of the patients self-reported to belong to Catholic or
      other Christian churches. There were few statistically significant differences
      between them and nonbelievers, who were younger, had more years of education,
      were more frequently employed, and lived alone or with their parents. When
      comparing the least religious and the most religious quartiles, there were no
      differences in the type of affective disorder, attendance to temples, or self
      appraisal of religiosity. Nonbelievers had more history of previous suicidal
      attempts and had more relatives committing suicide. DISCUSSION: In a country
      where most of the population is believer, self-reported religiosity seems to have
      a nonsignificant association with suicidality and severity of depression. Our
      results could be biased given the small number of nonbelievers in the sample.

PMID- 24019247
TI  - Sustained remission of severe Multicentric Castleman disease following multiagent
      chemotherapy and tocilizumab maintenance.
AB  - Castleman disease is a rare lymphoproliferative disorder, which presents in a
      unicentric or multicentric fashion. Multicentric Castleman disease (MCD) is
      associated with significant systemic symptoms, in part related to the underlying
      role of interleukin-6 in disease pathogenesis. Treatment for MCD has not been
      well established and prognosis has historically been poor. We present a case of
      severe MCD in a pediatric patient who has shown sustained remission following
      multi-agent chemotherapy and targeted maintenance therapy with the interleukin-6
      receptor inhibitor, tocilizumab. This represents the first case report of
      sustained remission of MCD in a pediatric patient following discontinuation of
      tocilizumab therapy.

PMID- 24019246
TI  - What skills should students of undergraduate biochemistry and molecular biology
      programs have upon graduation?
AB  - Biochemistry and molecular biology (BMB) students should demonstrate proficiency
      in the foundational concepts of the discipline and possess the skills needed to
      practice as professionals. To ascertain the skills that should be required,
      groups of BMB educators met in several focused workshops to discuss the
      expectations with the ultimate goal of clearly articulating the skills required.
      The results of these discussions highlight the critical importance of
      experimental, mathematical, and interpersonal skills including collaboration,
      teamwork, safety, and ethics. The groups also found experimental design, data
      interpretation and analysiand the ability to communicate findings to diverse
      audience to be essential skills. To aid in the development of appropriate
      assessments these skills are grouped into three categories, 1) Process of
      Science, 2) Communication and Comprehension of Science, and 3) Community of
      Practice Aspects of Science. Finally, the groups worked to align these
      competencies with the best practices in both teaching and in skills assessment.

PMID- 24019248
TI  - Capillary hemangiomatosis like-lesions in lung biopsies from children with
      congenital heart defects.
AB  - The morphological findings in the lung vessels of children with pulmonary
      arterial hypertension associated with uncorrected congenital cardiac shunts may
      be qualitatively and quantitatively assessed by lung biopsy in selected cases.
      Among 297 lung biopsies collected over a period of 11 years two cases were
      detected presenting the typical findings of pulmonary capillary hemangiomatosis,
      a rare disorder usually associated with pulmonary veno-occlusive disease. We
      report the clinical and histological findings and discuss about the impact of
      this unexpected and not-previously described associated lesion on the prognosis
      and on the therapeutic strategy in patients with pulmonary hypertension
      associated with congenital heart disease.

PMID- 24019249
TI  - Pain and somatic symptoms are sequelae of sexual assault: results of a
      prospective longitudinal study.
AB  - BACKGROUND: Cross-sectional studies have shown that chronic musculoskeletal pain
      and somatic symptoms are frequently reported by sexual assault (SA) survivors;
      however, prospective studies examining pain and somatic symptoms in the months
      after SA have not been performed. METHODS: Women SA survivors 18 years of age or
      older who presented for care within 48 h of SA were recruited. Pain in eight body
      regions (head and face, neck, breast, arms, abdomen, back, genital and pelvic,
      and legs) and 21 common somatic symptoms (e.g., headache, nausea, insomnia,
      persistent fatigue) were assessed (0-10 numeric rating scale in each body region)
      at the time of presentation, 1-week, 6-week and 3-month interview. Post-traumatic
      stress disorder (PTSD) symptoms were assessed at the 6-week and 3-month
      interview. RESULTS: Clinically significant new or worsening pain (CSNWP) symptoms
      were common among study participants 6 weeks after SA [43/74, 58% (95% CI, 47
      69%)] and 3 months after SA [40/67, 60% (95% CI, 48-71%)] and generally occurred
      in regions not experiencing trauma. Women SA survivors also experienced an
      increased burden of many common somatic symptoms: 8/21 (38%) and 11/21 (52%)
      common somatic symptoms showed a significant increase in severity 6 weeks and 3
      months after SA, respectively. Correlations between PTSD, CSNWP and somatic
      symptoms were only low to moderate, suggesting that these outcomes are distinct.
      CONCLUSIONS: New and/or clinically worsening pain and somatic symptoms, lasting
      at least 3 months, are sequelae of SA. Further studies investigating pain and
      somatic symptoms after SA are needed.

PMID- 24019250
TI  - Microfluidic-integrated biosensors: prospects for point-of-care diagnostics.
AB  - There is a growing demand to integrate biosensors with microfluidics to provide
      miniaturized platforms with many favorable properties, such as reduced sample
      volume, decreased processing time, low cost analysis and low reagent consumption.
      These microfluidics-integrated biosensors would also have numerous advantages
      such as laminar flow, minimal handling of hazardous materials, multiple sample
      detection in parallel, portability and versatility in design. Microfluidics
      involves the science and technology of manipulation of fluids at the micro- to
      nano-liter level. It is predicted that combining biosensors with microfluidic
      chips will yield enhanced analytical capability, and widen the possibilities for
      applications in clinical diagnostics. The recent developments in microfluidics
      have helped researchers working in industries and educational institutes to adopt
      some of these platforms for point-of-care (POC) diagnostics. This review focuses
      on the latest advancements in the fields of microfluidic biosensing technologies,
      and on the challenges and possible solutions for translation of this technology
      for POC diagnostic applications. We also discuss the fabrication techniques
      required for developing microfluidic-integrated biosensors, recently reported
      biomarkers, and the prospects of POC diagnostics in the medical industry. 

PMID- 24019251
TI  - Monitoring and promoting the impact of pedagogically related scholarship.

PMID- 24019252
TI  - Functional screening assays with neurons generated from pluripotent stem cell
      derived neural stem cells.
AB  - Rapid and effective drug discovery for neurodegenerative disease is currently
      impeded by an inability to source primary neural cells for high-throughput and
      phenotypic screens. This limitation can be addressed through the use of
      pluripotent stem cells (PSCs), which can be derived from patient-specific samples
      and differentiated to neural cells for use in identifying novel compounds for the
      treatment of neurodegenerative diseases. We have developed an efficient protocol
      to culture pure populations of neurons, as confirmed by gene expression analysis,
      in the 96-well format necessary for screens. These differentiated neurons were
      subjected to viability assays to illustrate their potential in future high
      throughput screens. We have also shown that organelles such as nuclei and
      mitochondria could be live-labeled and visualized through fluorescence,
      suggesting that we should be able to monitor subcellular phenotypic changes.
      Neurons derived from a green fluorescent protein-expressing reporter line of PSCs
      were live-imaged to assess markers of neuronal maturation such as neurite length
      and co-cultured with astrocytes to demonstrate further maturation. These studies
      confirm that PSC-derived neurons can be used effectively in viability and
      functional assays and pave the way for high-throughput screens on neurons derived
      from patients with neurodegenerative disorders. 

PMID- 24019253
TI  - High-throughput screening assays for estrogen receptor by using coumestrol, a
      natural fluorescence compound.
AB  - Estrogen receptor (ER) is a ligand-inducible transcriptional factor involving in
      cell growth, differentiation, and diseases, so detection and identification of
      compounds having estrogenic effects are of great importance in the drug discovery
      industry. We have developed and validated a rapid, simple, and homogeneous method
      that can detect estrogenic compounds. This human ERalpha/beta binding assay uses
      fluorescence polarization (FP) by applying an autofluorescent phytoestrogen,
      coumestrol (CS). A nonspecific adsorption assay shows that no obvious nonspecific
      adsorption is detected between CS and ERs. In the Scatchard plot analysis, the
      convex curve exhibits a positive cooperative binding, indicating that the binding
      of CS induces a conformational change of the ER to form a dimer and increases the
      affinity for the additional CS. In the Hill plot analysis, CS shows moderate
      binding affinity with both ERalpha and ERbeta, and the measured Kd of CS is 32.66
      uM and 36.14 uM, respectively, indicating that CS is applicable to the ER binding
      assay for determination of potent ligands of moderate binding affinity. Four
      typical ligands are selected to verify the ER binding assays, and the results are
      consistent with the reported data. All of above make the FP method based on CS
      suitable for high-throughput screening. 

PMID- 24019254
TI  - Pharmacologic characterization of a kinetic in vitro human co-culture
      angiogenesis model using clinically relevant compounds.
AB  - Angiogenesis, the formation of new vessels from preexisting vessels, involves
      multiple cell types acting in concert to cause endothelial cell proliferation,
      migration, and differentiation into microvascular arrays. Under pathologic
      conditions, microenvironment changes result in altered blood vessel production.
      Historically, in vitro angiogenesis assays study individual aspects of the
      process and tend to be variable, difficult to quantify, and limited in clinical
      relevance. Here, we describe a kinetic, quantitative, co-culture angiogenesis
      model and demonstrate its relevance to in vivo pharmacology. Similar to in vivo
      angiogenesis, a co-culture of human umbilical vein endothelial cells with normal
      human dermal fibroblasts remains sensitive to multiple cytokines, resulting in a
      concentration-dependent stimulation of tube formation over time. Treatment with
      axitinib, a selective vascular endothelial growth factor (VEGF) antagonist,
      inhibited VEGF-mediated tube length and branch point formation and was selective
      for inhibiting VEGF over basic fibroblast growth factor (bFGF), similar to
      previous studies. Conversely, an FGFR-1 selective compound, PD-161570, was more
      potent at inhibiting bFGF-mediated angiogenesis. These results demonstrate the
      cytokine dynamics, selective pharmacology, and translational application of this
      model system. Finally, combining quantitative angiogenic biology with kinetic,
      live-content imaging highlights the importance of using validated in vitro models
      in drug discovery research. 

PMID- 24019255
TI  - Validation of an algorithm to quantify changes in actin cytoskeletal
      organization.
AB  - The actin cytoskeleton plays an important role in most, if not all, processes
      necessary for cell survival. Given the fundamental role that the actin
      cytoskeleton plays in the progression of cancer, it is an ideal target for
      chemotherapy. Although it is possible to image the actin cytoskeleton in a high
      throughput manner, there is currently no validated method to quantify changes in
      the cytoskeleton in the same capacity, which makes research into its organization
      and the development of anticytoskeletal drugs difficult. We have validated the
      use of a linear feature detection algorithm, allowing us to measure changes in
      actin filament organization. Its ability to quantify changes associated with
      cytoskeletal disruption will make it a valuable tool in the development of
      compounds that target the cytoskeleton in cancer. Our results show that this
      algorithm can quantify cytoskeletal changes in a cell-based system after addition
      of both well-established and novel anticytoskeletal agents using either
      fluorescence microscopy or a high-content imaging approach. This novel method
      gives us the potential to screen compounds in a high-throughput manner for cancer
      and other diseases in which the cytoskeleton plays a key role. 

PMID- 24019257
TI  - Metabolic engineering of aroma components in fruits.
AB  - Plants have the ability to produce a diversity of volatile metabolites, which
      attract pollinators and seed dispersers and strengthen plant defense responses.
      Selection by plant breeders of traits such as rapid growth and yield leads, in
      many cases, to the loss of flavor and aroma quality in crops. How the aroma can
      be improved without affecting other fruit attributes is a major unsolved issue.
      Significant advances in metabolic engineering directed at improving the set of
      volatiles that the fruits emit has been aided by the characterization of enzymes
      involved in the biosynthesis of flavor and aroma compounds in some fruits.
      However, before this technology can be successfully applied to modulate the
      production of volatiles in different crops, further basic research is needed on
      the mechanisms that lead to the production of these compounds in plants. Here we
      review the biosynthesis and function of volatile compounds in plants, and the
      attempts that have been made to manipulate fruit aroma biosynthesis by metabolic
      engineering. In addition, we discuss the possibilities that molecular breeding
      offers for aroma enhancement and the implications of the latest advances in
      biotechnological modification of fruit flavor and aroma. 

PMID- 24019256
TI  - A high-content screen identifies novel compounds that inhibit stress-induced TDP
      43 cellular aggregation and associated cytotoxicity.
AB  - TDP-43 is an RNA binding protein found to accumulate in the cytoplasm of brain
      and spinal cord from patients affected with amyotrophic lateral sclerosis (ALS)
      and frontotemporal lobar degeneration (FTLD). Nuclear TDP-43 protein regulates
      transcription through several mechanisms, and under stressed conditions, it forms
      cytoplasmic aggregates that co-localize with stress granule (SG) proteins in cell
      culture. These granules are also found in the brain and spinal cord of patients
      affected with ALS and FTLD. The mechanism through which TDP-43 might contribute
      to neurodegenerative diseases is poorly understood. To investigate the
      pathophysiology of TDP-43 aggregation and to isolate potential therapeutic
      targets, we screened a chemical library of 75,000 compounds using high-content
      analysis with PC12 cells that inducibly express human TDP-43 tagged with green
      fluorescent protein (GFP). The screen identified 16 compounds that dose
      dependently decreased the TDP-43 inclusions without significant cellular toxicity
      or changes in total TDP-43 expression levels. To validate the effect, we tested
      compounds by Western blot analysis and in a Caenorhabditis elegans model that
      replicates some of the relevant disease phenotypes. The hits from this assay will
      be useful for elucidating regulation of TDP-43, stress granule response, and
      possible ALS therapeutics. 

PMID- 24019258
TI  - Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to
      orofacial neuropathic pain states in a rat model.
AB  - BACKGROUND: Injury to the trigeminal nerve often results in the development of
      chronic pain states including tactile allodynia, or hypersensitivity to light
      touch, in orofacial area, but its underlying mechanisms are poorly understood.
      Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4
      (TSP4) in dorsal spinal cord that correlates with neuropathic pain development.
      In this study, we examined whether injury-induced TSP4 is critical in mediating
      orofacial pain development in a rat model of chronic constriction injury to the
      infraorbital nerve. METHODS: Orofacial sensitivity to mechanical stimulation was
      examined in a unilateral infraorbital nerve ligation rat model. The levels of
      TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2
      spinal cord (Vc/C2) from injured rats were examined at time points correlating
      with the initiation and peak orofacial hypersensitivity. TSP4 antisense and
      mismatch oligodeoxynucleotides were intrathecally injected into injured rats to
      see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4
      up-regulation and orofacial behavioural hypersensitivity. RESULTS: Our data
      indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a
      time point correlated with orofacial tactile allodynia. In addition, intrathecal
      treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked
      both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity.
      CONCLUSIONS: Our data support that infraorbital nerve injury leads to TSP4 up
      regulation in trigeminal spinal complex that contributes to orofacial neuropathic
      pain states. Blocking this pathway may provide an alternative approach in
      management of orofacial neuropathic pain states.

PMID- 24019261
TI  - Problem-solving test: conditional gene targeting using the Cre/loxP recombination
      system.
AB  - Terms to be familiar with before you start to solve the test: gene targeting,
      knock-out mutation, bacteriophage, complementary base-pairing, homologous
      recombination, deletion, transgenic organisms, promoter, polyadenylation element,
      transgene, DNA replication, RNA polymerase, Shine-Dalgarno sequence, restriction
      endonuclease, polymerase chain reaction, primer, transcription, SV40 virus,
      malignant transformation, spacer region, gene expression, agarose gel
      electrophoresis, ethidium bromide staining, Southern-blotting, probe, reporter
      gene.

PMID- 24019260
TI  - Information provision and information needs in adult survivors of childhood
      cancer.
AB  - BACKGROUND: Knowledge about their past medical history is central for childhood
      cancer survivors to ensure informed decisions in their health management.
      Knowledge about information provision and information needs in this population is
      still scarce. We thus aimed to assess: (1) the information survivors reported to
      have received on disease, treatment, follow-up, and late effects; (2) their
      information needs in these four domains and the format in which they would like
      it provided; (3) the association with psychological distress and quality of life
      (QoL). PROCEDURE: As part of the Follow-up survey of the Swiss Childhood Cancer
      Survivor Study, we sent a questionnaire to all survivors (>=18 years) who
      previously participated to the baseline survey, were diagnosed with cancer after
      1990 at an age of <16 years. RESULTS: Most survivors had received oral
      information only (on illness: oral: 82%, written: 38%, treatment: oral: 79%,
      written: 36%; follow-up: oral: 77%, written: 23%; late effects: oral: 68%,
      written: 14%). Most survivors who had not previously received any information
      rated it as important, especially information on late effects (71%). A large
      proportion of survivors reported current information needs and would like to
      receive personalized information especially on late effects (44%). Survivors with
      higher information needs reported higher psychological distress and lower QoL.
      CONCLUSIONS: Survivors want to be more informed especially on possible late
      effects, and want to receive personalized information. Improving information
      provision, both qualitatively and quantitatively, will allow survivors to have
      better control of their health and to become better decision makers.

PMID- 24019259
TI  - Anti-PcrV antibody in cystic fibrosis: a novel approach targeting Pseudomonas
      aeruginosa airway infection.
AB  - Pseudomonas aeruginosa (Pa) airway infection is associated with increased
      morbidity and mortality in cystic fibrosis (CF). The type III secretion system is
      one of the factors responsible for the increased virulence and pro-inflammatory
      effects of Pa. KB001 is a PEGylated, recombinant, anti-Pseudomonas-PcrV antibody
      Fab' fragment that blocks the function of Pa TTSS. We studied the safety,
      pharmacokinetic (PK), and pharmacodynamic properties of KB001 in CF subjects with
      chronic Pa infection. Twenty-seven eligible CF subjects (>=12 years of age, FEV1
      >=40% of predicted, and sputum Pa density >10(5)  CFU/g) received a single
      intravenous dose of KB001 (3 mg/kg or 10 mg/kg) or placebo. Safety, PK, Pa
      density, clinical outcomes, and inflammatory markers were assessed. KB001 had an
      acceptable safety profile and a mean serum half-life of 11.9 days. All subjects
      had Pa TTSS expression in sputum. There were no significant differences between
      KB001 and placebo for changes in Pa density, symptoms, or spirometry after a
      single dose. However, compared to baseline, at Day 28 there was a trend towards a
      dose-dependent reduction in sputum myeloperoxidase, IL-1, and IL-8, and there
      were significant overall differences in change in sputum neutrophil elastase and
      neutrophil counts favoring the KB001 10 mg/kg group versus placebo (-0.61 log(10)
      and -0.63 log(10) , respectively; P < 0.05). These results support targeting Pa
      TTSS with KB001 as a nonantibiotic strategy to reduce airway inflammation and
      damage in CF patients with chronic Pa infection. Repeat-dosing studies are
      necessary to evaluate the durability of the anti-inflammatory effects and how
      that may translate into clinical benefit. (NCT00638365).

PMID- 24019262
TI  - Does high blood pressure reduce the risk of chronic low back pain? The Nord
      Trondelag Health Study.
AB  - BACKGROUND: Epidemiological studies have suggested inverse relationships between
      blood pressure and prevalence of conditions such as migraine and headache. It is
      not yet clear whether similar relationships can be established for back pain in
      particular in prospective studies. METHODS: Associations between blood pressure
      and chronic low back pain were explored in the cross-sectional HUNT 2 survey of a
      Norwegian county in 1995-1997, including 39,872 individuals who never used
      antihypertensive medication. A prospective study, comprising 17,209 initially
      back pain-free individuals and 5740 individuals reporting low back pain, was
      established by re-examinations in the HUNT 3 survey in 2006-2008. Associations
      were assessed by logistic regression with respect to systolic, diastolic and
      pulse pressure, with adjustment for education, work status, physical activity,
      smoking, body mass and lipid levels. RESULTS: In the cross-sectional study, all
      three blood pressure measures showed inverse relationships with prevalence of low
      back pain in both sexes. In the prospective study of disease-free women, baseline
      pulse pressure and systolic pressure were inversely associated with risk of low
      back pain [odds ratio (OR) 0.93 per 10 mm Hg increase in pulse pressure, 95%
      confidence interval (CI) 0.89-0.98, p = 0.007; OR 0.95 per 10 mm Hg increase in
      systolic pressure, 95% CI 0.92-0.99, p = 0.005]. Results among men were
      equivocal. No associations were indicated with the occurrence of pain in
      individuals with low back pain at baseline. CONCLUSIONS: Results for low back
      pain are consistent with the theory of hypertension-associated hypalgesia,
      predicting diminished pain sensitivity with increasing blood pressure, possibly
      with modified reactions in people suffering from long-lasting pain.

PMID- 24019263
TI  - A phase II window study of irinotecan (CPT-11) in high risk Ewing sarcoma: a Euro
      E.W.I.N.G. study.
AB  - BACKGROUND: The prognosis for patients with nonpulmonary metastatic Ewing sarcoma
      remains poor with survival in the order of 15-20%. The need to introduce
      effective new agents into clinical practice is clear. Based on a preclinical
      rationale of responses in xenografts and backed by a phase I study in children,
      the Euro-E.W.I.N.G consortium planned a phase II window study of irinotecan in
      newly diagnosed high risk metastatic patients with Ewing sarcoma. PROCEDURES:
      Patients were recruited between April 2004 and December 2007. Two courses of
      irinotecan were administered at a dose of 600 mg/m(2) as a 1 hour infusion at 21
      day intervals. Response evaluation was determined after the second course of
      treatment by radiological assessment of primary and metastatic sites and, where
      appropriate bone marrow sampling. RESULTS: Twenty-three patients were recruited.
      Two patients were deemed inevaluable for response. Five patients (24%)
      demonstrated a partial response. Grade 3 or 4 diarrhoea was seen in 4/43 course
      of treatment and was managed with loperamide. CONCLUSIONS: This is the first
      report of single agent irinotecan activity in an untreated population of patients
      with Ewing sarcoma. In common with other paediatric tumours and other
      camptothecin analogues such as topotecan, single agent activity is only modest.
      The exact role for the use of irinotecan in patients with ES, dose schedule and
      combinations with other agents still requires further investigation.

PMID- 24019264
TI  - Beta-defensin-2 genomic copy number variation and chronic periodontitis.
AB  - Chronic periodontitis (ChP) is a multifactorial disease influenced by microbial
      and host genetic variability; however, the role of beta-defensin-2 genomic
      (DEFB4) copy number (CN) variation (V) in ChP remains unknown. The association of
      the occurrence and severity of ChP and DEFB4 CNV was analyzed. Our study included
      227 unrelated Caucasians, that is, 136 ChP patients (combined ChP) and 91 control
      individuals. The combined ChP group was subdivided into the severe ChP and slight
      to-moderate ChP subgroups. To determine DEFB4 CNV, we isolated genomic DNA
      samples and analyzed them by relative quantitation using the comparative CT
      method. The serum beta-defensin-2 (hBD-2) level was determined via ELISA. The
      distribution pattern and mean DEFB4 CN did not differ significantly in combined
      ChP cases vs. the controls; however, the mean DEFB4 CN in the severe ChP group
      differed significantly from those for the control and slight-to-moderate ChP
      groups. Low DEFB4 CN increased the risk of severe ChP by about 3-fold. DEFB4 CN
      was inversely associated with average attachment loss. Mean serum hBD-2 levels
      were highest in the controls, followed by the slight-to-moderate ChP group and
      the severe ChP group. The results suggested an association between decreased
      DEFB4 CN and serum hBD-2 levels and periodontitis severity. 

PMID- 24019265
TI  - Affordable hands-on DNA sequencing and genotyping: an exercise for teaching DNA
      analysis to undergraduates.
AB  - In this report, we describe a 5-week laboratory exercise for undergraduate
      biology and biochemistry students in which students learn to sequence DNA and to
      genotype their DNA for selected single nucleotide polymorphisms (SNPs). Students
      use miniaturized DNA sequencing gels that require approximately 8 min to run. The
      students perform G, A, T, C Sanger sequencing reactions. They prepare and run the
      gels, perform Southern blots (which require only 10 min), and detect sequencing
      ladders using a colorimetric detection system. Students enlarge their sequencing
      ladders from digital images of their small nylon membranes, and read the sequence
      manually. They compare their reads with the actual DNA sequence using BLAST2.
      After mastering the DNA sequencing system, students prepare their own DNA from a
      cheek swab, polymerase chain reaction-amplify a region of their DNA that
      encompasses a SNP of interest, and perform sequencing to determine their genotype
      at the SNP position. A family pedigree can also be constructed. The SNP chosen by
      the instructor was rs17822931, which is in the ABCC11 gene and is the determinant
      of human earwax type. Genotypes at the rs178229931 site vary in different ethnic
      populations.

PMID- 24019267
TI  - Energy drink consumption is associated with anxiety in Australian young adult
      males.
AB  - BACKGROUND: Energy drinks are predominantly targeted to young adult consumers;
      however, there has been limited research into their effects on psychological
      functioning in this demographic group. This study examined cross-sectional
      associations between energy drink consumption and mental health in a population
      based sample of young adults participating in the Western Australian Pregnancy
      Cohort (Raine) Study. METHODS: We used self-report questionnaires to assess
      energy drink consumption and mental health (Depression Anxiety Stress Scale-21;
      DASS-21) at the 20-year cohort follow-up. In the regression analyses, we
      considered associations between energy drink consumption (mL/day) and continuous
      DASS-21 scores, adjusting for sociodemographic variables, alcohol and drug use,
      physical activity, body mass index (BMI), and dietary intake. Our sample included
      502 males and 567 females (mean age 20 +/- 3 years). RESULTS: After adjusting for
      potential confounding factors and controlling for coexisting mental health
      problems, energy drink consumption (per 100 mL/day) was significantly associated
      with anxiety (but not depression or stress), and this relationship was found only
      in males (beta = 0.32; 95% CI = 0.05, 0.58). CONCLUSIONS: Our study found that
      energy drink consumption was associated with increased anxiety in young adult
      males. Further research into the possible contribution of energy drink use to the
      development of mental health problems in young adults is needed.

PMID- 24019268
TI  - Two-photon polarity probes built from octupolar fluorophores: synthesis,
      structure-properties relationships, and use in cellular imaging.
AB  - A series of octupolar fluorophores built from a triphenylamine (TPA) core
      connected to electron-withdrawing (EW) peripheral groups through conjugated
      spacers has been synthesized. Their photoluminescence, solvatochromism, and two
      photon absorption (2PA) properties were systematically investigated to derive
      structure-property relationships. All derivatives exhibit two 2PA bands in the
      700-1000 nm region: a first band at low energy correlated with a core-to
      periphery intramolecular charge transfer that leads to an intense 1PA in the blue
      visible range, and a second more intense band at higher energy due to an
      efficient coupling of the branches through the TPA core. Increasing the strength
      of the EW end groups or the length of the conjugated spacers and replacing triple
      bond linkers with double bonds induces both enhancement and broadening of the 2PA
      responses, thereby leading to cross-sections up to 2100 GM at peak and higher
      than 1000 GM over the whole 700-900 nm range. All derivatives exhibit intense
      photoluminescence (PL) in low- to medium-polarity environments (with quantum
      yields in the 0.5-0.9 range) and display a strong positive solvatochromic
      behavior (with Lippert-Mataga specific shifts ranging from 15,000 to 27,500 cm(
      1)), triple bonds, and phenyl moieties in the conjugated spacers, thereby leading
      to larger sensitivities than those of double bonds and thienyl moieties. More
      hydrophilic derivatives were also shown to be biocompatible, to retain their 2PA
      and PL properties in biological conditions, and finally to be suitable as
      polarity sensors for multiphoton cell imaging.

PMID- 24019266
TI  - Molecular mechanisms underlying neuronal synaptic plasticity: systems biology
      meets computational neuroscience in the wilds of synaptic plasticity.
AB  - Interactions among signaling pathways that are activated by transmembrane
      receptors produce complex networks and emergent dynamical behaviors that are
      implicated in synaptic plasticity. Temporal dynamics and spatial aspects are
      critical determinants of cell responses such as synaptic plasticity, although the
      mapping between spatiotemporal activity pattern and direction of synaptic
      plasticity is not completely understood. Computational modeling of neuronal
      signaling pathways has significantly contributed to understanding signaling
      pathways underlying synaptic plasticity. Spatial models of signaling pathways in
      hippocampal neurons have revealed mechanisms underlying the spatial distribution
      of extracellular signal-related kinase (ERK) activation in hippocampal neurons.
      Other spatial models have demonstrated that the major role of anchoring proteins
      in striatal and hippocampal synaptic plasticity is to place molecules near their
      activators. Simulations of yet other models have revealed that the spatial
      distribution of synaptic plasticity may differ for potentiation versus
      depression. In general, the most significant advances have been made by
      interactive modeling and experiments; thus, an interdisciplinary approach should
      be applied to investigate critical issues in neuronal signaling pathways. These
      issues include identifying which transmembrane receptors are key for activating
      ERK in neurons, and the crucial targets of kinases that produce long-lasting
      synaptic plasticity. Although the number of computer programs for computationally
      efficient simulation of large reaction-diffusion networks is increasing,
      parameter estimation and sensitivity analysis in these spatial models remain more
      difficult than in single compartment models. Advances in live cell imaging
      coupled with further software development will continue to accelerate the
      development of spatial models of synaptic plasticity.

PMID- 24019269
TI  - The Affordable Care Act: unprecedented opportunities for family physicians and
      public health.

PMID- 24019270
TI  - The Affordable Care Act: objectives and likely results in an imperfect world.

PMID- 24019271
TI  - Potential adult Medicaid beneficiaries under the Patient Protection and
      Affordable Care Act compared with current adult Medicaid beneficiaries.
AB  - PURPOSE: Under health care reform, states will have the opportunity to expand
      Medicaid to millions of uninsured US adults. Information regarding this
      population is vital to physicians as they prepare for more patients with
      coverage. Our objective was to describe demographic and health characteristics of
      potentially eligible Medicaid beneficiaries. METHODS: We performed a cross
      sectional study using data from the National Health and Nutrition Examination
      Survey (2007-2010) to identify and compare adult US citizens potentially eligible
      for Medicaid under provisions of the Patient Protection and Affordable Care Act
      (ACA) with current adult Medicaid beneficiaries. We compared demographic
      characteristics (age, sex, race/ethnicity, education) and health measures (self
      reported health status; measured body mass index, hemoglobin A1c level, systolic
      and diastolic blood pressure, depression screen [9-item Patient Health
      Questionnaire], tobacco smoking, and alcohol use). RESULTS: Analyses were based
      on an estimated 13.8 million current adult non-elderly Medicaid beneficiaries and
      13.6 million nonelderly adults potentially eligible for Medicaid. Potentially
      eligible individuals are expected to be more likely male (49.2% potentially
      eligible vs 33.3% current beneficiaries; P <.001), to be more likely white and
      less likely black (58.8% white, 20.0% black vs 49.9% white, 25.2% black; P =
      .02), and to be statistically indistinguishable in terms of educational
      attainment. Overall, potentially eligible adults are expected to have better
      health status (34.8% "excellent" or "very good," 40.4% "good") than current
      beneficiaries (33.5% "excellent" or "very good," 31.6% "good"; P <.001). The
      proportions obese (34.5% vs 42.9%; P = .008) and with depression (15.5% vs 22.3%;
      P = .003) among potentially eligible individuals are significantly lower than
      those for current beneficiaries, while there are no significant differences in
      the expected prevalence of diabetes or hypertension. Current tobacco smoking
      (49.2% vs 38.0%; P = .002), and moderate and heavier alcohol use (21.6% vs 16.0%
      and 16.5% vs 9.8%; P <.001, respectively) are more common among the potentially
      eligible population than among current beneficiaries. CONCLUSIONS: Under the ACA,
      physicians can anticipate a potentially eligible Medicaid population with equal
      if not better current health status and lower prevalence of obesity and
      depression than current Medicaid beneficiaries. Federal Medicaid expenditures for
      newly covered beneficiaries therefore may not be as high as anticipated in the
      short term. Given the higher prevalence of tobacco smoking and alcohol use,
      however, broad enrollment and engagement of this potentially eligible population
      is needed to address their higher prevalence of modifiable risk factors for
      future chronic disease.

PMID- 24019272
TI  - Abbreviated mindfulness intervention for job satisfaction, quality of life, and
      compassion in primary care clinicians: a pilot study.
AB  - PURPOSE: Burnout, attrition, and low work satisfaction of primary care physicians
      are growing concerns and can have a negative influence on health care.
      Interventions for clinicians that improve work-life balance are few and poorly
      understood. We undertook this study as a first step in investigating whether an
      abbreviated mindfulness intervention could increase job satisfaction, quality of
      life, and compassion among primary care clinicians. METHODS: A total of 30
      primary care clinicians participated in an abbreviated mindfulness course. We
      used a single-sample, pre-post design. At 4 points in time (baseline, and 1 day,
      8 weeks, and 9 months postintervention), participants completed a set of online
      measures assessing burnout, anxiety, stress, resilience, and compassion. We used
      a linear mixed-effects model analysis to assess changes in outcome measures.
      RESULTS: Participants had improvements compared with baseline at all 3 follow-up
      time points. At 9 months postintervention, they had significantly better scores
      (1) on all Maslach Burnout Inventory burnout subscales-Emotional Exhaustion (P
      =.009), Depersonalization (P = .005), and Personal Accomplishment (P <.001); (2)
      on the Depression (P =.001), Anxiety (P =.006), and Stress (P = .002) subscales
      of the Depression Anxiety Stress Scales-21; and (3) for perceived stress (P =
      .002) assessed with the Perceived Stress Scale. There were no significant changes
      on the 14-item Resilience Scale and the Santa Clara Brief Compassion Scale.
      CONCLUSIONS: In this uncontrolled pilot study, participating in an abbreviated
      mindfulness training course adapted for primary care clinicians was associated
      with reductions in indicators of job burnout, depression, anxiety, and stress.
      Modified mindfulness training may be a time-efficient tool to help support
      clinician health and well-being, which may have implications for patient care.

PMID- 24019273
TI  - A multicenter study of physician mindfulness and health care quality.
AB  - PURPOSE: Mindfulness (ie, purposeful and nonjudgmental attentiveness to one's own
      experience, thoughts, and feelings) is associated with physician well-being. We
      sought to assess whether clinician self-rated mindfulness is associated with the
      quality of patient care. METHODS: We conducted an observational study of 45
      clinicians (34 physicians, 8 nurse practitioners, and 3 physician assistants)
      caring for patients infected with the human immunodeficiency virus (HIV) who
      completed the Mindful Attention Awareness Scale and 437 HIV-infected patients at
      4 HIV specialty clinic sites across the United States. We measured patient
      clinician communication quality with audio-recorded encounters coded using the
      Roter Interaction Analysis System (RIAS) and patient ratings of care. RESULTS: In
      adjusted analyses comparing clinicians with highest and lowest tertile
      mindfulness scores, patient visits with high-mindfulness clinicians were more
      likely to be characterized by a patient-centered pattern of communication
      (adjusted odds ratio of a patient-centered visit was 4.14; 95% CI, 1.58-10.86),
      in which both patients and clinicians engaged in more rapport building and
      discussion of psychosocial issues. Clinicians with high-mindfulness scores also
      displayed more positive emotional tone with patients (adjusted beta = 1.17; 95%
      CI, 0.46-1.9). Patients were more likely to give high ratings on clinician
      communication (adjusted prevalence ratio [APR] = 1.48; 95% CI, 1.17-1.86) and to
      report high overall satisfaction (APR = 1.45; 95 CI, 1.15-1.84) with high
      mindfulness clinicians. There was no association between clinician mindfulness
      and the amount of conversation about biomedical issues. CONCLUSIONS: Clinicians
      rating themselves as more mindful engage in more patient-centered communication
      and have more satisfied patients. Interventions should determine whether
      improving clinician mindfulness can also improve patient health outcomes.

PMID- 24019274
TI  - Vaccinations administered during off-clinic hours at a national community
      pharmacy: implications for increasing patient access and convenience.
AB  - PURPOSE: Approximately 50,000 adults die annually from vaccine-preventable
      diseases in the United States. Most traditional vaccine providers (eg, physician
      offices) administer vaccinations during standard clinic hours, but community
      pharmacies offer expanded hours that allow patients to be vaccinated at
      convenient times. We analyzed the types of vaccines administered and patient
      populations vaccinated during off-clinic hours in a national community pharmacy,
      and their implications for vaccination access and convenience. METHODS: We
      retrospectively reviewed data for all vaccinations given at the Walgreens
      pharmacy chain between August 2011 and July 2012. The time of vaccination was
      categorized as occurring during traditional hours (9:00 am-6:00 pm weekdays) or
      off-clinic hours, consisting of weekday evenings, weekends, and federal holidays.
      We compared demographic characteristics and types of vaccine. We used a logistic
      regression model to identify predictors of being vaccinated during off-clinic
      hours. RESULTS: During the study period, pharmacists administered 6,250,402
      vaccinations, of which 30.5% were provided during off-clinic hours: 17.4% were
      provided on weekends, 10.2% on evenings, and 2.9% on holidays. Patients had
      significantly higher odds of off-clinic vaccination if they were younger than 65
      years of age, were male, resided in an urban area, and did not have any chronic
      conditions. CONCLUSIONS: A large proportion of adults being vaccinated receive
      their vaccines during evening, weekend, and holiday hours at the pharmacy, when
      traditional vaccine providers are likely unavailable. Younger, working-aged,
      healthy adults, in particular, a variety of immunizations during off-clinic
      hours. With the low rates of adult and adolescent vaccination in the United
      States, community pharmacies are creating new opportunities for vaccination that
      expand access and convenience.

PMID- 24019275
TI  - Natural course of cutaneous warts among primary schoolchildren: a prospective
      cohort study.
AB  - PURPOSE: Because cutaneous warts resolve spontaneously and available treatments
      often fail, family physicians and patients may consider a wait-and-see policy. We
      examined the natural course of cutaneous warts and treatment decisions in a
      prospective observational cohort of primary schoolchildren. METHODS: We inspected
      the hands and feet of children aged 4 to 12 years from 3 Dutch primary schools
      for the presence of warts at baseline and after a mean follow-up of 15 months.
      Parental questionnaires at follow-up provided information on inconvenience caused
      by warts and any treatments used. RESULTS: Of the 1,134 eligible children, 1,099
      (97%) participated, of whom 366 (33%) had cutaneous warts at baseline. Among
      these children with warts, loss to follow-up was 9% and the response rate to the
      parental questionnaires was 83%. The complete resolution rate was 52 per 100
      person-years at risk (95% CI, 44-60). Younger age (hazard ratio = 1.1 per year
      decrease; 95% CI, 1.0-1.2) and non-Caucasian skin type (hazard ratio = 2.0; 95%
      CI, 1.3-2.9) increased the likelihood of resolution. During follow-up, 38% of
      children with warts at baseline treated their warts: 18% used over-the-counter
      treatment only, 15% used a family physician-provided treatment only, and 5% used
      both. Children were more likely to initiate treatment if the warts measured at
      least 1 cm in diameter (odds ratio = 3.2; 95% CI, 1.9-5.3) and especially if
      parents reported that the warts caused inconvenience (odds ratio = 38; 95% CI, 16
      90). CONCLUSIONS: One-half of primary schoolchildren with warts will be free of
      warts within 1 year. Young age and non-Caucasian skin type enhance resolution.
      Children with large or inconvenient warts are more likely to start treatment.
      These findings will be useful in the process of shared decision making with
      parents and children.

PMID- 24019276
TI  - Toward a simple diagnostic index for acute uncomplicated urinary tract
      infections.
AB  - PURPOSE: Whereas a diagnosis of acute uncomplicated urinary tract infection (UTI)
      in clinical practice comprises a battery of several diagnostic tests, these tests
      are often studied separately (in isolation from other test results). We wanted to
      determine the value of history and urine tests for diagnosis of uncomplicated
      UTIs, taking into account their mutual dependencies and information from
      preceding tests. METHODS: Women with painful and/or frequent micturition answered
      questions about their signs and symptoms (history) of UTIs and underwent urine
      tests. A culture was the reference standard (10(3) colony-forming units per
      milliliter). A diagnostic index was derived using logistic regression with
      bootstrapped backward selection and parameter-wise shrinkage. Risk thresholds for
      UTI of 30% and 70% were used to analyze discriminative properties. Six models
      were compared: (1) history only, (2) history+ urine dipstick, (3) history+ urine
      dipstick + urinary sediment, (4) history+ urine dipstick+ dipslide, and (5)
      history+ urine dipstick+ urinary sediment+ dipslide; we then added (6) a test
      only for patients with an intermediate risk (between 30% and 70%) after the
      preceding test. RESULTS: One hundred ninety-six women were included (UTI
      prevalence 61%). Seven variables were selected from history (3), dipstick (2),
      sediment (1), and dipslide (1). History correctly classified 56% of patients as
      having a UTI risk of either <30% or >70%. History and urine dipstick raised this
      to 73%. The 3 models with the addition of urinary sediment and dipslide,
      separately and in combination, performed hardly better. The sixth model, in which
      those at intermediate risk after history and received an additional test,
      correctly classified 83%. The patient's suspicion of a UTI and a positive nitrite
      test were the strongest indicators of a UTI. CONCLUSIONS: Most women with painful
      and/or frequent micturition can be correctly classified as having either a low or
      a high risk of UTI by asking 3 questions: Does the patient think she has a UTI?
      Is there at least considerable pain on micturition? Is there vaginal irritation?
      Other women require additional urine dipstick investigation. Sediment and
      dipslide have little added value. External validation of these recommendations is
      required before they are implemented in practice.

PMID- 24019278
TI  - eCHAT for lifestyle and mental health screening in primary care.
AB  - PURPOSE: Early detection and management of unhealthy behaviors and mental health
      issues in primary care has the potential to prevent or ameliorate many chronic
      diseases and increase patients' well-being. This study aimed to assess the
      feasibility and acceptability of the systematic use of a Web-based eCHAT
      (electronic Case-finding and Help Assessment Tool) screening patients for
      problematic drinking, smoking, and other drug use, gambling, exposure to abuse,
      anxiety, depression, anger control, and physical inactivity, and whether they
      want help with these issues. Patients self-administered eCHAT on an iPad in the
      waiting room and received summarized results, including relevant scores and
      interpretations, which could be by a family physician on the website and in the
      electronic health record (EHR) at the point of care. METHODS: We conducted a
      mixed method feasibility and acceptability study in 2 general practices in
      Auckland, New Zealand. Participants were consecutive adult patients attending the
      practice during a 2-week period, as well as all practice staff. Patients
      completed eCHAT, doctors accessed the summarized reports. Outcome measures were
      patients' responses to eCHAT, and patients' written and staff recorded interview
      feedback. RESULTS: Of the 233 invited patients, 196 (84%) completed eCHAT and
      received feedback. Domains where patients wanted immediate help were anxiety
      (9%), depression (7%), physical activity (6%), and smoking (5%), which was not
      overwhelming for physicians to address. Most patients found the iPad easy to use,
      and the questions easy to understand and appropriate; they did not object to
      questions. Feedback from 7 doctors, 2 practice managers, 4 nurses, and 5
      receptionists was generally positive. Practices continue to use eCHAT regularly
      since the research was completed. CONCLUSIONS: eCHAT is an acceptable and
      feasible means of systemic screening patients for unhealthy behaviors and
      negative mood states and is easily integrated into the primary care electronic
      health record.

PMID- 24019277
TI  - Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis.
AB  - PURPOSE: Cinnamon has been studied in randomized controlled trials (RCTs) for its
      glycemic-lowering effects, but studies have been small and show conflicting
      results. A prior meta-analysis did not show significant results, but several RCTs
      have been published since then. We conducted an updated systematic review and
      meta-analysis of RCTs evaluating cinnamon's effect on glycemia and lipid levels.
      METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials
      (CENTRAL) were searched through February 2012. Included RCTs evaluated cinnamon
      compared with control in patients with type 2 diabetes and reported at least one
      of the following: glycated hemoglobin (A1c), fasting plasma glucose, total
      cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density
      lipoprotein cholesterol (HDL-C), or triglycerides. Weighted mean differences
      (with 95% confidence intervals) for endpoints were calculated using random
      effects models. RESULTS: In a meta-analysis of 10 RCTs (n = 543 patients),
      cinnamon doses of 120 mg/d to 6 g/d for 4 to 18 weeks reduced levels of fasting
      plasma glucose (-24.59 mg/dL; 95% CI, -40.52 to -8.67 mg/dL), total cholesterol (
      15.60 mg/dL; 95% CI, -29.76 to -1.44 mg/dL), LDL-C (-9.42 mg/dL; 95% CI, -17.21
      to -1.63 mg/dL), and triglycerides (-29.59 mg/dL; 95% CI, -48.27 to -10.91
      mg/dL). Cinnamon also increased levels of HDL-C (1.66 mg/dL; 95% CI, 1.09 to 2.24
      mg/dL). No significant effect on hemoglobin A1c levels (-0.16%; 95%, CI -0.39% to
      0.02%) was seen. High degrees of heterogeneity were present for all analyses
      except HDL-C (I(2) ranging from 66.5% to 94.72%). CONCLUSIONS: The consumption of
      cinnamon is associated with a statistically significant decrease in levels of
      fasting plasma glucose, total cholesterol, LDL-C, and triglyceride levels, and an
      increase in HDL-C levels; however, no significant effect on hemoglobin A1c was
      found. The high degree of heterogeneity may limit the ability to apply these
      results to patient care, because the preferred dose and duration of therapy are
      unclear.

PMID- 24019279
TI  - Relationship between clinical quality and patient experience: analysis of data
      from the english quality and outcomes framework and the National GP Patient
      Survey.
AB  - PURPOSE: Clinical quality and patient experience are both widely used to evaluate
      the quality of health care, but the relationship between these 2 domains remains
      uncertain. The aim of this study was to examine this relationship using data from
      2 established measures of quality in primary care in England. METHODS: Practice
      level analyses (N = 7,759 practices in England) were conducted on measures of
      patient experience from the national General Practice Patient Survey (GPPS), and
      measures of clinical quality from the national pay-for-performance scheme
      (Quality and Outcomes Framework). Spearman's rank correlation and multiple linear
      regression were used on practice-level estimates. RESULTS: Although all the
      correlations between clinical quality summary scores and patient survey scores
      are positive, and most are statistically significant, the strength of the
      associations was weak, with the highest correlation coefficient reaching 0.18,
      and more than one-half were 0.11 or less. Correlations with clinical quality were
      highest for patient-reported access scores (telephone access 0.16, availability
      of urgent appointments 0.15, ability to book ahead 0.18, ability to see preferred
      doctor 0.17) and overall satisfaction (0.15). CONCLUSION: Although there are
      associations between clinical quality and measures of patient experience, the 2
      domains of care quality remain predominantly distinct. The strongest correlations
      are observed between practice clinical quality and practice access, with very low
      correlations between clinical quality and interpersonal aspects of care. The
      quality of clinical care and the quality of interpersonal care should be
      considered separately to give an overall assessment of medical care.

PMID- 24019280
TI  - Being uninsured is bad for your health: can medical homes play a role in treating
      the uninsurance ailment?
AB  - In the United States, stable health insurance coverage is associated with
      improved health outcomes. A lack of insurance is associated with premature death
      from preventable causes. Although primary care clinicians are often in a position
      to see firsthand the impact that being uninsured has on patients, most ambulatory
      care clinics are not actively involved in helping patients obtain health
      insurance, retain their coverage, or make important health insurance coverage
      decisions. The magnitude and complexity of the US "uninsurance" problem, as well
      as recent federal initiatives to expand coverage options, inspire important
      questions: Can medical homes play a more active role in helping patients find and
      keep insurance coverage? How can basic tenets from the chronic care model be
      operationalized to build systems to treat the uninsurance ailment? Creating
      effective processes and tools within the medical home to keep a patient insured
      may be as important to improving population health as helping a patient maintain
      a normal blood pressure. Similar system-level interventions could be used to
      support both endeavors. 

PMID- 24019281
TI  - Measuring up: musings of a family doctor on the employee time clock.
AB  - Recently, at the health maintenance organization (HMO) where I work, they
      introduced an employee time clock. As in many other workplaces, doctors across
      the country are now obligated to punch the clock at the beginning and end of
      their workday. This is the final act in an ongoing attempt to enhance management
      of doctors' schedules: limit nonurgent appointments to 10 minutes, define planned
      or urgent home visits, and control a physician's time, as well as managerial and
      clinical decisions. In this story I describe a day in the life of a family
      doctor, a salaried employee at a large HMO where there is now a time clock. I
      provide details on how the introduction of the clock influences small everyday
      clinical decisions that potentially affect the quality and depth of treatment
      while sharing the internal dialogue that accompanies me as I reaffirm my
      professional integrity again and again with each hastened visit. I also bring the
      internal dialogue of 2 of my patients, to illustrate the emotional world on the
      other side of these 10-minute interventions. 

PMID- 24019283
TI  - University of Missouri's "reincarnated" workshop for new chairs of Departments of
      Family Medicine.

PMID- 24019284
TI  - AFMRD FMCC scholarships.

PMID- 24019286
TI  - AHRQ updates on primary care research: multiple chronic conditions research
      network.

PMID- 24019287
TI  - CMS proposes new codes in 2014 fee schedule to benefit family physicians.

PMID- 24019289
TI  - Robotic radical hysterectomy following neoadjuvant chemotherapy in FIGO stage
      IIIB cervical cancer: a case report.
AB  - BACKGROUND: The management of advanced cervical cancer is challenging. The
      administration of neoadjuvant chemotherapy (NACT) followed by radical
      hysterectomy has proved to be safe in selected cases. Nevertheless, data on the
      use of minimally invasive surgery is lacking with this clinical application.
      METHODS: A 31 year-old woman was diagnosed with a FIGO stage IIIB squamous cell
      cervical carcinoma. During multidisciplinary consultation it was decided that she
      should receive NACT, followed by robotic hysterectomy. RESULTS: After three
      cycles of TIP (paclitaxel, ifosfamide and cisplatin), the patient achieved a
      complete clinical and radiological response. She underwent robotic type III/C2
      radical hysterectomy with bilateral salpingo-oophorectomy and bilateral
      systematic pelvic lymphadenectomy. No complications were recorded. The complete
      response was confirmed at pathological examination. Two additional cycles of
      adjuvant chemotherapy were administered, and the patient is currently without
      evidence of disease at 18 months of follow-up. CONCLUSIONS: In selected patients,
      robotics is a viable option to accomplish radical hysterectomy, including cases
      of advanced cervical cancer. Further experiences are needed to confirm our
      findings.

PMID- 24019288
TI  - Systems biology approaches to epidemiological studies of complex diseases.
AB  - Systems biology approaches to epidemiological studies of complex diseases include
      collection of genetic, genomic, epigenomic, and metagenomic data in large-scale
      epidemiological studies of complex phenotypes. Designs and analyses of such
      studies raise many statistical challenges. This article reviews some issues
      related to integrative analysis of such high dimensional and inter-related
      datasets and outline some possible solutions. I focus my review on integrative
      approaches for genome-wide genetic variants and gene expression data, methods for
      joint analysis of genetic and epigenetic variants, and methods for analysis of
      microbiome data. Statistical methods such as mediation analysis, high-dimensional
      instrumental variable regression, sparse signal recovery, and compositional data
      regression provide potential frameworks for integrative analysis of these high
      dimensional genomic data.

PMID- 24019290
TI  - Chiral scandium(III)-catalyzed enantioselective alpha-arylation of N-unprotected
      3-substituted oxindoles with diaryliodonium salts.

PMID- 24019291
TI  - Primary ammonium monocarboxylate synthon in designing supramolecular gels: a new
      series of chiral low-molecular-weight gelators derived from simple organic salts
      that are capable of generating and stabilizing gold nanoparticles.
AB  - The primary ammonium monocarboxylate (PAM) synthon has been exploited to generate
      a new series of PAM salts from the free amine of L-phenylalanine-3-pyridyl amide,
      (S)-2-amino-3-phenyl-N-(pyridine-3-yl)propanamine (designated as "B"), and
      various substituted benzoic acids (designated as "A(R)"; R=4-Me, 4-Cl, 4-Br, 4
      NO2, 3-Me, 3-Cl, 3-Br, 3-NO2, 2-Me, 2-Cl, 2-Br, 2-NO2). The 4- and 3-substituted
      benzoate salts showed moderate-to-excellent gelation ability with a number of
      polar and apolar solvents. The gels were characterized by DSC, rheology, SEM and
      TEM, FTIR spectroscopy, etc. Structure-property studies based on single-crystal
      powder X-ray diffraction (PXRD) and FTIR data provided insights into the role of
      the PAM synthon in the formation of the gel networks. Interestingly, some of the
      gels were capable of forming and stabilizing gold nanoparticles at room
      temperature without the use of any exogenous reducing agents.

PMID- 24019292
TI  - Asymmetric copolymerization of CO2 with meso-epoxides mediated by dinuclear
      cobalt(III) complexes: unprecedented enantioselectivity and activity.
AB  - Unprecedented enantioselectivity and catalytic activity was observed in the
      asymmetric copolymerization of CO2 with meso-epoxides (including the less
      reactive cyclopentene oxide) mediated by the dinuclear Co(III) complex (S,S,S,S)
      1 under mild conditions. The resultant copolymers possess more than 99 %
      carbonate linkages and a perfectly isotactic structure. 

PMID- 24019293
TI  - Prevalence of use of performance enhancing drugs by fitness centre members.
AB  - Studies on the use of performance enhancing drugs (PED) in fitness centres rely
      predominately on conventional survey methods using direct questioning. However,
      research indicates that direct questioning of sensitive information is
      characterized by under-reporting. The aim of the present study was to contrast
      direct questioning of different types of PED use by Dutch fitness centre members
      with results obtained with the Randomized Response Technique (RRT).
      Questionnaires were conducted among members of fitness centres. PED were
      classified into the following categories: anabolic steroids, prohormones,
      substances to counteract side-effects, growth hormone and/or insulin, stimulants
      (to reduce weight), and miscellaneous substances. A total of 718 athletes from 92
      fitness centres completed the questionnaire. The conventional method resulted in
      prevalences varying between 0% and 0.4% for the different types of PED with an
      overall prevalence of 0.4%. RRT resulted in prevalences varying between 0.8% and
      4.8% for the different types of PED with an overall prevalence of 8.2%. The
      overall prevalence of the two survey methods differed significantly. The current
      study showed that the conventional survey method using direct questioning led to
      an underestimation of the prevalence. Based on the RRT results, the percentage of
      users of PED among members of fitness centres is approximately 8.2%. Stimulants
      to lose weight had the highest prevalence, even higher than anabolic steroids.
      The key task for future preventive health work is to not only focus on anabolic
      steroid use, but also include interventions focusing on the use of stimulants to
      lose weight.

PMID- 24019294
TI  - Magnesium metal--a potential biomaterial with antibone cancer properties.
AB  - Reactive oxygen plays an important role in the pathogenesis of many serious
      illnesses, including bony cancer. Recently, it has been suggested that hydrogen
      (H2), a selective antioxidant, can effectively scavenge free radicals. Biomedical
      magnesium (Mg) used for bone defect repair in the surgery of bony cancer could
      release H2 because of the degradation, so Mg might have the potential to prevent
      bony cancer from metastasis and recurrence. In this study, alkali-heat treatment
      method was employed to modify the surface structure of Mg metal, so as to control
      the degradation of Mg metal and the H2 releasing rate. Then the released H2 was
      introduced to the Fenton Reaction system to detect its effect on scavenging free
      radicals. The modified Mg metal was employed as the substrate for bone cancer
      cell culture to study the effect of the H2 releasing on scavenging free radicals
      in the cells. It is found that the H2 released from the Mg degradation could
      scavenge free radicals both in the Fenton Reaction system and bone cancer cells.
      The effect on the scavenging free radical is proportional to the rate of H2
      releasing. It suggested that Mg might be a potential material with anti-bone
      cancer properties. It is hopeful to both repair the bone defect and prevent bony
      cancer from metastasis and recurrence for the bony cancer patients by biomedical
      Mg metal.

PMID- 24019295
TI  - Nutritional content of infant commercial weaning foods in the UK.
AB  - BACKGROUND AND AIMS: Health professionals are frequently asked to advise on
      aspects of complementary feeding. This study aimed to describe the types of
      commercial infant foods available in the UK and provide an overview of their
      taste, texture and nutritional content in terms of energy, protein,
      carbohydrates, fat, sugar, iron, sodium and calcium. METHOD: All infant foods
      produced by four main UK manufacturers and two more specialist suppliers were
      identified during October 2010-February 2011. Nutritional information for each
      product was collected from manufacturers' websites, products in store and via
      direct email enquiry. RESULTS: Of the 479 products identified in this study 364
      (79%) were ready-made spoonable foods; 44% (201) were aimed at infants from 4
      months, and 65% of these were sweet foods. The mean (SD) energy content of ready
      made spoonable foods was 282 (59) kJ per 100 g, almost identical to breast milk
      (283(16) kJ per 100 g). Similar spoonable family foods were more nutrient dense
      than commercial foods. Commercial finger foods were more energy dense, but had
      very high sugar content. CONCLUSIONS: The UK infant food market mainly supplies
      sweet, soft, spoonable foods targeted from age 4 months. The majority of products
      had energy content similar to breast milk and would not serve the intended
      purpose of enhancing the nutrient density and diversity of taste and texture in
      infants' diets.

PMID- 24019296
TI  - Hydrogen and carbon isotope fractionation during degradation of chloromethane by
      methylotrophic bacteria.
AB  - Chloromethane (CH3 Cl) is a widely studied volatile halocarbon involved in the
      destruction of ozone in the stratosphere. Nevertheless, its global budget still
      remains debated. Stable isotope analysis is a powerful tool to constrain fluxes
      of chloromethane between various environmental compartments which involve a
      multiplicity of sources and sinks, and both biotic and abiotic processes. In this
      study, we measured hydrogen and carbon isotope fractionation of the remaining
      untransformed chloromethane following its degradation by methylotrophic bacterial
      strains Methylobacterium extorquens CM4 and Hyphomicrobium sp. MC1, which belong
      to different genera but both use the cmu pathway, the only pathway for bacterial
      degradation of chloromethane characterized so far. Hydrogen isotope fractionation
      for degradation of chloromethane was determined for the first time, and yielded
      enrichment factors (epsilon) of -290/00 and -270/00 for strains CM4 and MC1,
      respectively. In agreement with previous studies, enrichment in (13) C of
      untransformed CH3 Cl was also observed, and similar isotope enrichment factors
      (epsilon) of -410/00 and -380/00 were obtained for degradation of chloromethane
      by strains CM4 and MC1, respectively. These combined hydrogen and carbon isotopic
      data for bacterial degradation of chloromethane will contribute to refine models
      of the global atmospheric budget of chloromethane. 

PMID- 24019297
TI  - Systematic investigation of elevated transaminases during the third
      posttransplant month.

PMID- 24019298
TI  - Ethical considerations in consenting critically ill patients for bedside clinical
      care and research.
AB  - Care of critically ill patients, as in any other field, demands the exercise of
      ethical principles related to respect of patient's autonomy, beneficence,
      nonmaleficence, and distributive justice. Professional duty and the common law
      require doctors to obtain consent before giving treatment or for requesting
      participation in clinical research. A procedure or research study must be
      adequately explained, and the patient must have the capacity to consent. If a
      patient does not have decision-making capacity, treatment must be given using
      alternative forms of consent or using principles of implied consent in emergency
      or life-threatening situations. In the case of clinical research, informed
      consent must always be sought. Exemptions to this rule are morally justified in
      circumstances related to research in life-threatening conditions or life-saving
      interventions in which the investigator departs from sound principles of
      equipoise. This usually implies the imposition of safeguards such as consultation
      with the community in which the study were to take place, oversight in patient
      screening and recruitment process by institutional review boards, special study
      designs, retrospective and prospective consent processes, and independent safety
      monitoring. 

PMID- 24019299
TI  - A patient with trauma having cavitary pulmonary nodules: should further workup be
      pursued?
AB  - BACKGROUND: Traumatic pulmonary pseudocysts (TPPs) are rare sequelae of blunt
      chest trauma and may be incidentally visualized on initial, or subsequent, chest
      imaging. CASE: We present the case of a 37-year-old male with no past medical
      history, who was recently hospitalized in the intensive care unit after a motor
      vehicle accident and referred to our institution for a traumatic cataract repair.
      His preoperative chest radiograph revealed multiple left-sided pulmonary nodules
      that were confirmed on thoracic computed tomography (CT) and noted to be
      cavitary. Comparison of the films to prior imaging, negative infectious workup,
      and absence of any symptoms led to the diagnosis of TPPs. Follow-up imaging
      showed complete resolution of the lesions. CONCLUSION: The TPPs may be discovered
      on imaging shortly after blunt chest trauma and, in asymptomatic individuals, can
      often be monitored with observation and serial imaging.

PMID- 24019300
TI  - Massive intravascular hemolysis from Clostridium perfringens septicemia: a
      review.
AB  - We describe the case of a patient with hemolysis-associated Clostridium
      perfringens septicemia and review all similar cases published in the literature
      since 1990, with specific focus on the relationship between treatment strategy
      and survival. We searched PubMed for all published cases of C. perfringens
      associated hemolysis, using the medical subject terms "clostridia," "clostridial
      sepsis," and/or "hemolysis." All case reports, case series, review articles, and
      other relevant references published in the English literature since 1990 were
      included in this study. There were no exclusion criteria. Each case was examined
      with respect to presenting features of illness, antibiotic regimen, time-to
      antibiotic therapy, additional interventions, complications, and patient
      survival. These variables were entered into a data set and then systematically
      analyzed with the aid of a statistician, using serial t tests and chi-square
      analyses. Since 1990, 50 patients of C. perfringens septicemia with hemolysis
      have been reported. Median age was 61 years (range 31-84), and 58% were male.
      Mortality was 74%, with a median time to death of 9.7 hours (range 0-96 hours).
      Of the patients, 35 (70%) were treated medically, while 15 (30%) received
      antibiotics and surgery. Surgical intervention was associated with significantly
      improved survival (risk ratio [RR] 0.23, 95% confidence interval [CI] 0.10, 0.53)
      as was the use of a combination of penicillin and clindamycin (RR of death 0.46,
      95% CI 0.25, 0.83). Four patients utilizing hyperbaric oxygen therapy (HBOT) have
      been reported, and all patients survived. In cases of clostridial sepsis with
      hemolysis, strong predictors of survival include early initiation of appropriate
      antibiotics as well as surgical removal of infected foci. The HBOT may also be
      associated with survival. The disease often progresses rapidly to death, so rapid
      recognition is critical for the patient survival. 

PMID- 24019301
TI  - SOX12 and NRSN2 are candidate genes for 20p13 subtelomeric deletions associated
      with developmental delay.
AB  - 20p13 telomeric/subtelomeric deletions are clinically significant but are
      currently under-investigated. So far only five molecularly delineated cases have
      been reported in literature and no candidate genes have been sufficiently
      implicated. Here, we present six new deletion cases identified by chromosomal
      microarray analysis (CMA). We also review 32 cases combined from literature and
      databases. We found that most 20p13 deletion patients exhibit significant
      developmental delay. Dysmorphic features are common but a consistent pattern was
      not recognized. Reduced cognitive ability was frequent. Based on pathogenic
      deletions delineated in this study, we mapped the smallest overlapping region and
      identified two nervous system expressing genes (SOX12 and NRSN2) as candidate
      genes that may be involved in the developmental defects in 20p13 microdeletion.

PMID- 24019302
TI  - Nitrite impacts the survival of Mycobacterium tuberculosis in response to
      isoniazid and hydrogen peroxide.
AB  - When access to molecular oxygen is restricted, Mycobacterium tuberculosis (Mtb)
      can respire an alternative electron acceptor, nitrate. We found that Mtb within
      infected primary human macrophages in vitro at physiologic tissue oxygen tensions
      respired nitrate, generating copious nitrite. A strain of Mtb lacking a
      functioning nitrate reductase was more susceptible than wild-type Mtb to
      treatment with isoniazid during infection of macrophages. Likewise, nitrate
      reductase-deficient Mtb was more susceptible to isoniazid than wild-type Mtb in
      axenic culture, and more resistant to hydrogen peroxide. These phenotypes were
      reversed by the addition of exogenous nitrite. Further investigation suggested
      that nitrite might inhibit the bacterial catalase. To the extent that Mtb itself
      is the most relevant source of nitrite acting within Mtb, these findings suggest
      that inhibitors of Mtb's nitrate transporter or nitrate reductase could enhance
      the efficacy of isoniazid. 

PMID- 24019303
TI  - Effects of n-3 PUFA on the CD4+ type 2 helper T-cell-mediated immune responses in
      Fat-1 mice.
AB  - SCOPE: It has been suggested that n-3 PUFA can be used as a preventive or
      therapeutic strategy to control allergic asthma. But little is known about the
      exact mechanisms by which n-3 PUFA modulates it. Here, the effects of elevated n
      3 PUFA on ovalbumin (OVA) induced airway inflammation were investigated using Fat
      1 transgenic mice that can convert n-6 PUFA to n-3 PUFA endogenously. METHODS AND
      RESULTS: First, we tested whether Fat-1 expression modulates CD4+ T-cell
      activation, proliferation, and differentiation in vitro and found that the Fat-1
      expression attenuated all of these CD4+ T-cell responses by suppression of T-cell
      receptor mediated signaling and cytokine-mediated phosphorylation of STATs. When
      the Fat-1 mice were sensitized and challenged with the OVA, they showed a
      significant decrease in the recruitment of inflammatory cells into airway, the
      production of Th2 cytokines, eotaxin, and mucin in the lung, and the
      concentration of OVA-specific IgE in the serum. Furthermore, the differentiation
      of CD4+ T cells into Th2 was also decreased in the spleen of Fat-1 mice.
      CONCLUSION: Our results showed that an elevated level of n-3 PUFA was effective
      in preventing allergic airway inflammation by modulating the activation and
      differentiation of CD4+ T cells in Fat-1 mice.

PMID- 24019304
TI  - Which is the goal of cognitive rehabilitation in multiple sclerosis: the
      improvement of cognitive performance or the perception of cognitive deficits?

PMID- 24019305
TI  - Comparing long-term results of PASAT and SDMT scores in relation to
      neuropsychological testing in multiple sclerosis.
AB  - BACKGROUND AND OBJECTIVES: The Symbol Digit Modalities Test (SDMT) shows
      advantages over the Paced Auditory Serial Addition Test (PASAT) as a cognitive
      test in patients with multiple sclerosis (MS). To determine which of these tests
      is most valid and reliable over time as an indicator of the cognitive state of MS
      patients, long-term test results of both tests were compared in relation to
      scores of the Brief Repeatable Battery of Neuropsychological tests (BRBN).
      METHODS: For 485 MS patients visiting the VU University Medical Center Amsterdam
      for different research projects, a total number of 1078 visits with BRBN
      (including PASAT and SDMT) was planned. Observed and model-based correlations
      were used to calculate the construct validity of the SDMT and PASAT 3 seconds
      test (PASAT3) by comparing correlations with the BRBN-sumscore. The test-retest
      reliability of each test was also computed. RESULTS: For the construct validity,
      higher correlations were found between SDMT and BRBN compared to PASAT3 and BRBN,
      especially for the model-based correlations at baseline. The reliability of the
      measurements was good for all instruments, with the highest coefficients for the
      SDMT. CONCLUSION: As a single assessment tool for cognition in MS, the SDMT is
      more valid and reliable compared to PASAT3.

PMID- 24019306
TI  - Nurses' perception of ethical climate and organizational commitment.
AB  - The high turnover of nurses has become a universal issue. The manner in which
      nurses view their organization's ethical climate has direct bearing on their
      organizational commitment. The aim of this study was to determine the correlation
      between nurses' perception of ethical climate and organizational commitment in
      teaching hospitals in the southeastern region of Iran. A descriptive analytical
      design was used in this study. The sample consisted of 275 nurses working in four
      teaching hospitals in the southeastern region of Iran. The instruments used in
      this study included a demographic questionnaire, Ethical Climate Questionnaire,
      and Organizational Commitment Questionnaire. Data analysis was carried out using
      Pearson's correlation, t-test, and descriptive statistic through Statistical
      Package for Social Science, version 16. The result of this research indicated a
      positive correlation among professionalism, caring, rules, independence climate,
      and organizational commitment. Therefore, findings of this study are a guideline
      for researchers and managers alike who endeavor to improve organizational
      commitment. 

PMID- 24019307
TI  - Hiding the plot: parents' moral dilemmas and strategies when helping their
      overweight children lose weight.
AB  - In this study we investigated the moral dilemmas and strategies of a group of
      Danish parents who were trying to help their overweight children lose weight.
      Data were drawn from repeated semistructured interviews carried out over a period
      of 2 years with 12 families with overweight children. Using a narrative approach,
      we show the moral dilemmas parents found themselves in when trying to further the
      two seemingly incompatible goals of helping their children lose weight and
      simultaneously strengthening their self-worth. When the children were young, the
      parents tried to hide the fact that they needed to lose weight to protect them
      from feeling stigmatized. As the children grew older, the parents became more
      forthright about weight loss so the children would take on more responsibility.
      We suggest that for parents, weight loss is experienced as a risky undertaking
      because they perceive their children's self-worth as being in jeopardy during the
      process. 

PMID- 24019308
TI  - Endoscopic removal of symptomatic gastric heterotopic pancreas: a report of nine
      cases.
AB  - AIMS: The aim of this study was to evaluate the efficacy and safety of endoscopic
      removal of symptomatic gastric heterotopic pancreas (HP). PATIENTS AND METHODS:
      From January 2010 to December 2011, 9 patients with suspected symptomatic HP were
      enrolled in the study. Endoscopic ultrasonography was performed to clarify the HP
      tissue location and to choose the endoscopic resection method. Endoscopic mucosal
      resection or endoscopic submucosal dissection was performed to remove the HP
      tissue. Symptoms in the enrolled patients were assessed before and after
      endoscopic removal of the HP tissue. Tumor pathology and complications were
      recorded after the treatment. A standard follow-up was scheduled at 1 week and 2
      months after treatment. RESULTS: Removal of suspected HP with endoscopic mucosal
      resection or endoscopic submucosal dissection was successful in all 9 cases.
      Abdominal pain, leukocytosis, and bleeding occurred in 6 patients, 2 patients,
      and 1 patient, respectively, after treatment and were relieved by symptomatic
      treatment. There were no other unpredictable complications. The symptoms related
      to HP, including epigastric pain, bloating, and postprandial fullness, were
      relieved significantly after the treatment. During follow-up, there was no
      recurrence of HP in any patient. CONCLUSIONS: Endoscopic removal appears to be a
      safe and effective method to treat gastric lesions suspected to be HP with
      symptoms. The symptoms, such as epigastric pain, bloating, and postprandial
      fullness were well resolved after endoscopic treatment.

PMID- 24019317
TI  - Q&A: Crystal Mackall, John Maris on pediatrics.

PMID- 24019318
TI  - Stopping breast cancer before it starts.

PMID- 24019329
TI  - Epigenetic approaches for chemosensitization of refractory diffuse large B-cell
      lymphomas.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin
      lymphoma, with the greatest challenge for improving patient survival being the
      management of chemorefractory disease upon relapse. Epigenetic dysregulation has
      been correlated with more-aggressive malignancies and chemoresistance. In this
      issue of Cancer Discovery, Clozel and colleagues show the potential for low-dose
      DNA methyltransferase inhibitors as both a rational and an effective neoadjuvant
      approach for chemosensitization in DLBCL.

PMID- 24019330
TI  - Resistance emerges to second-generation antiandrogens in prostate cancer.
AB  - The appearance of a mutant androgen receptor, AR(F876L), in prostate cancer cells
      chronically exposed to enzalutamide or ARN-509 promotes a switch from antagonist
      to agonist receptor function, undermining the potential long-term effectiveness
      of these second-generation antiandrogen drugs.

PMID- 24019331
TI  - Say what? The activity of the polyamine biosynthesis inhibitor
      difluoromethylornithine in chemoprevention is a result of reduced thymidine
      pools?
AB  - In this issue of Cancer Discovery, Witherspoon and colleagues use an unbiased
      metabolite profiling approach to study the effects of polyamine depletion by 2
      difluoromethylornithine in colon cancer cells. Their surprising findings indicate
      that it is a decrease in thymidine pools resulting from altered tetrahydrofolate
      availability rather than decreases in polyamines that produces cytostasis.

PMID- 24019352
TI  - Neoplastic and nonneoplastic lesions in aging mice of unique and common inbred
      strains contribution to modeling of human neoplastic diseases.
AB  - The evaluation of spontaneous lesions in classical inbred strains of mice has
      become increasingly important because genetically engineered mice (GEMs) are
      created on these backgrounds. Novel inbred strains-genetically diverse from
      classic strains-are valuable both as a new background for GEM mice and to
      increase the genetic variation found in laboratory mice. Newly arising
      spontaneous genetic alterations in commonly used strains may also lead to new and
      valuable mouse models of disease. This report evaluates gross and histological
      lesions in relatively new, classic, and rarely explored mouse inbred strains.
      Pathological lesions of 1273 mice from 12 inbred strains (129S1/SvW, A.CA-H2(f)
      /W, AKR/W, BALB/cW, BN/aW, C57BL/6 W, C57BL/10 W, C3H/W, C3H (wad) /W, CBA/W,
      DBA/2 W, and WOM/W) are reported. BN/aW, WOM/W, and C3H (wad) /W are novel inbred
      strains produced and maintained in the Department of Genetics and Laboratory
      Animal Breeding at the Center of Oncology, Warsaw, Poland. Both neoplastic and
      nonneoplastic lesions were examined. The prevalence of lung neoplasms was
      significantly higher in A.CA-H2(f) /W (33.3%) and BALB/cW (33.8%) mice (P < .01).
      The prevalence of liver neoplasms was significantly higher in the CBA/W strain (P
      < .01). Mammary gland neoplasms arose at a greater frequency in C3H/W mice (P <
      .01). The occurrence of uterine neoplasms was higher in DBA/W and 129S1/SvW mice.
      AKR/W and WOM/W mice developed T-cell lymphoblastic lymphoma with high frequency
      (110/121 [90.9%] and 159/175 [90.9%], respectively) before 1 year of age. The
      occurrence of nonneoplastic lesions in the kidneys of BN/aW mice was increased (P
      < .01).

PMID- 24019353
TI  - Implementing the ACA: onward through the thorns.

PMID- 24019354
TI  - The essential role of food and farm policy in improving health.

PMID- 24019355
TI  - Will employers drop health insurance coverage because of the Affordable Care Act?
AB  - Since the passage of the Affordable Care Act, there has been much speculation
      about how many employers will stop offering health insurance once the act's major
      coverage provisions take effect. Some observers predict little aggregate effect,
      but others believe that 2014 will mark the beginning of the end for our current
      system of employer-sponsored insurance. We use theoretical and empirical evidence
      to address the question, "How will employers' offerings of health insurance
      change under health reform?" First, we describe the economic reasons why
      employers offer insurance. Second, we recap the relevant provisions of health
      reform and use our economic framework to consider how they may affect employers'
      offerings. Third, we review the various predictions that have been made about
      those offerings under health reform. Finally, we offer some observations on
      interpreting early data from 2014.

PMID- 24019356
TI  - Small increases to employer premiums could shift millions of people to the
      exchanges and add billions to federal outlays.
AB  - The Affordable Care Act will expand insurance coverage to more than twenty-five
      million Americans, partly through subsidized private insurance available from
      newly created health insurance exchanges for people with incomes of 133-400
      percent of the federal poverty level. The act will alter the financial incentive
      structure for employers and influence their decisions on whether or not to offer
      their employees coverage. These decisions, in turn, will affect federal outlays
      and revenues through several mechanisms. We model the sensitivity of federal
      costs for the insurance exchange coverage provision of the Affordable Care Act
      using the nationally representative Medical Expenditure Panel Survey data set. We
      assess revenues and subsidy outlays for premiums and cost sharing for individuals
      purchasing private insurance through exchanges. Our findings show that changing
      theoretical premium contribution levels by just $100 could induce 2.25 million
      individuals to transition to exchanges and increase federal outlays by $6.7
      billion. Policy makers and analysts should pay especially careful attention to
      participation rates as the act's implementation continues.

PMID- 24019357
TI  - Large repayments of premium subsidies may be owed to the IRS if family income
      changes are not promptly reported.
AB  - Subsidies for health insurance premiums under the Affordable Care Act are
      refundable tax credits. They can be taken when taxes are filed or in advance, as
      reductions in monthly premiums that must be reconciled at tax filing. Recipients
      who take subsidies in advance will receive tax refunds if their subsidies were
      too small but will have to make repayments if their subsidies were too high. We
      analyzed predicted repayments and refunds for people receiving subsidies, using
      California as a case study. We found that many families could owe large
      repayments to the Internal Revenue Service at their next tax filing. If income
      changes were reported and credits adjusted in a timely manner throughout the tax
      year, the number of filers owing repayments would be reduced by 7-41 percent and
      the median size of repayments reduced by as much as 61 percent (depending on the
      level of changes reported and the method used to adjust the subsidy amounts). We
      recommend that the health insurance exchanges mandated by the Affordable Care Act
      educate consumers about how the subsidies work and the need to promptly report
      income changes. We also recommend that they provide tools and assistance to
      determine the amount of subsidies that enrollees should take in advance.

PMID- 24019358
TI  - Impact of medical loss regulation on the financial performance of health
      insurers.
AB  - The Affordable Care Act's regulation of medical loss ratios requires health
      insurers to use at least 80-85 percent of the premiums they collect for direct
      medical expenses (care delivery) or for efforts to improve the quality of care.
      To gauge this rule's effect on insurers' financial performance, we measured
      changes between 2010 and 2011 in key financial ratios reflecting insurers'
      operating profits, administrative costs, and medical claims. We found that the
      largest changes occurred in the individual market, where for-profit insurers
      reduced their median administrative cost ratio and operating margin by more than
      two percentage points each, resulting in a seven-percentage-point increase in
      their median medical loss ratio. Financial ratios changed much less for insurers
      in the small- and large-group markets.

PMID- 24019359
TI  - Medicaid expansion: chronically homeless adults will need targeted enrollment and
      access to a broad range of services.
AB  - Homeless adults may gain access to health services under the Affordable Care
      Act's Medicaid expansion, which takes effect in 2014. This study analyzed the
      health coverage, health status, and health services use of 725 chronically
      homeless adults with disabilities in eleven cities in the United States. Nearly
      three-quarters of the chronically homeless adults in this study with incomes
      below the threshold for the Medicaid expansion were not enrolled in Medicaid.
      Fifty-three percent were uninsured or relied solely on state or local assistance,
      and 21 percent had other coverage that included Department of Veterans Affairs
      health care. The findings on differences in health status and service use across
      groups suggest that the Medicaid expansion offers important opportunities to
      increase coverage and access to care for chronically homeless adults. There may
      be potential savings for states that expand Medicaid, as people transition from
      state and local assistance to more comprehensive services under Medicaid.
      Targeted outreach and assistance to enroll eligible homeless people will be
      necessary. A broad range of physical and mental health services will be required,
      including case management to coordinate services.

PMID- 24019360
TI  - Physicians may need more than higher reimbursements to expand Medicaid
      participation: findings from Washington State.
AB  - The expansion of insurance coverage under the Affordable Care Act is expected to
      put considerable pressure on the capacity of the primary care workforce to meet
      the needs of the Medicaid population beginning in 2014. The results from a 2011
      survey and focus-group sessions with Washington State primary care physicians
      suggest that doctors welcome planned increases in Medicaid reimbursement rates.
      However, the data also show that other approaches could be even more effective in
      increasing physicians' willingness to see Medicaid patients. Those approaches
      include lowering the costs of participating in Medicaid by simplifying
      administrative processes, speeding up reimbursement, and reducing the costs
      associated with caring for those patients. In focus groups, physicians were
      cautiously optimistic about the potential of the Affordable Care Act to make a
      difference in each of these areas, with electronic health records, medical homes,
      and accountable care organizations all seen as promising developments.

PMID- 24019361
TI  - Survey of high-risk pool enrollees suggests that targeted transition education
      and outreach should begin soon.
AB  - Several provisions of the Affordable Care Act make state and federal high-risk
      pools unnecessary beginning in January 2014. As a result, thousands of enrollees
      in those pools will be transferred to Medicaid and the new state and federal
      insurance exchanges. Our study analyzed new survey data collected from enrollees
      in the country's oldest and largest state-based high-risk pool, the Minnesota
      Comprehensive Health Association. We estimate that approximately half of the
      enrollees in that pool will qualify for Medicaid or premium subsidies in the
      exchange. More than 60 percent of the enrollees reported being somewhat or very
      unfamiliar with health care reform and the resulting changes to their current
      coverage. Their concerns about the expected impact of health reform varied by
      income, geography, and level of deductible. Targeting education and outreach
      information to address these concerns will be critical for this population's
      smooth transition to new coverage.

PMID- 24019362
TI  - Continuous-eligibility policies stabilize Medicaid coverage for children and
      could be extended to adults with similar results.
AB  - A key method of stabilizing Medicaid coverage is to provide beneficiaries with
      twelve months of continuous eligibility. Following the passage of the Children's
      Health Insurance Program Reauthorization Act in 2009, seven states adopted the
      continuous-eligibility option for children. That policy change led to a 1.8
      percentage-point increase in the average length of child enrollment during fiscal
      year 2010 and increased annual costs for children by about 2.2 percent. The
      Medicaid and CHIP Payment and Access Commission has recommended offering states
      the option of giving adults twelve-month continuous eligibility for Medicaid. Our
      findings suggest that continuous eligibility could promote more stable coverage
      for adults enrolled in Medicaid at a modest cost.

PMID- 24019363
TI  - Private insurers' payments for routine physician office visits vary substantially
      across the United States.
AB  - Anecdotal reports suggest that substantial variation exists in private insurers'
      payments for physician services, but systematic evidence is lacking. Using a
      retrospective analysis of insurance claims for routine office visits,
      consultations, and preventive visits from more than forty million physician
      claims in 2007, we examined variations in private payments to physicians and the
      extent to which variation is explained by patients' and physicians'
      characteristics and by geographic region. We found much variation in payments for
      these routine evaluation and management services. Physicians at the high end of
      the payment distribution were generally paid more than twice what physicians at
      the low end were paid for the same service. Little variation was explained by
      patients' age or sex, physicians' specialty, place of service, whether the
      physician was a "network provider," or type of plan, although about one-third of
      the variation was associated with the geographic area of the practice.
      Interventions that promote more price-consciousness on the part of patients could
      help reduce health care spending, but more data on the specific causes of price
      variation are needed to determine appropriate policy responses.

PMID- 24019364
TI  - The cost of overtriage: more than one-third of low-risk injured patients were
      taken to major trauma centers.
AB  - Regionalized trauma care has been widely implemented in the United States, with
      field triage by emergency medical services (EMS) playing an important role in
      identifying seriously injured patients for transport to major trauma centers. In
      this study we estimated hospital-level differences in the adjusted cost of acute
      care for injured patients transported by 94 EMS agencies to 122 hospitals in 7
      regions, overall and by injury severity. Among 301,214 patients, the average
      adjusted per episode cost of care was $5,590 higher in a level 1 trauma center
      than in a nontrauma hospital. We found hospital-level differences in cost among
      patients with minor, moderate, and serious injuries. Of the 248,342 low-risk
      patients-those who did not meet field triage guidelines for transport to trauma
      centers-85,155 (34.3 percent) were still transported to major trauma centers,
      accounting for up to 40 percent of acute injury costs. Adhering to field triage
      guidelines that minimize the overtriage of low-risk injured patients to major
      trauma centers could save up to $136.7 million annually in the seven regions we
      studied.

PMID- 24019365
TI  - Emergency department visits after surgery are common for Medicare patients,
      suggesting opportunities to improve care.
AB  - Considerable attention is being paid to hospital readmission as a marker of poor
      postdischarge care coordination. However, little is known about another potential
      marker: emergency department (ED) use. We examined ED visits for Medicare
      patients within thirty days of discharge for six common inpatient surgeries. We
      found that these visits were widespread and showed extensive variation across
      facilities. For example, 17.3 percent of these patients experienced at least one
      ED visit within the postdischarge period, and 4.4 percent of patients had
      multiple ED visits. Among those patients who were readmitted, 56.5 percent were
      readmitted from the ED. There was substantial variation-as much as fourfold-in
      hospital-level ED use for these patients across all six procedures. The variation
      might signify a failure in upstream coordination of care and therefore might
      represent a novel hospital quality indicator. In addition, the postdischarge ED
      visit is an opportunity to ensure that care is properly coordinated and is the
      last best chance to avoid preventable readmissions.

PMID- 24019366
TI  - Geographic health information systems: a platform to support the 'triple aim'.
AB  - Despite the rapid growth of electronic health data, most data systems do not
      connect individual patient records to data sets from outside the health care
      delivery system. These isolated data systems cannot support efforts to recognize
      or address how the physical and environmental context of each patient influences
      health choices and health outcomes. In this article we describe how a geographic
      health information system in Durham, North Carolina, links health system and
      social and environmental data via shared geography to provide a multidimensional
      understanding of individual and community health status and vulnerabilities.
      Geographic health information systems can be useful in supporting the Institute
      for Healthcare Improvement's Triple Aim Initiative to improve the experience of
      care, improve the health of populations, and reduce per capita costs of health
      care. A geographic health information system can also provide a comprehensive
      information base for community health assessment and intervention for accountable
      care that includes the entire population of a geographic area.

PMID- 24019367
TI  - Quality measurement combined with peer review improved German in-hospital
      mortality rates for four diseases.
AB  - Mortality rates during hospital stays for common diseases show considerable
      variation at the hospital level, which suggests that there is potential for
      outcome improvement. We studied changes in mortality after an intervention that
      aimed to improve medical outcomes through quality measurement combined with peer
      review. We examined eighteen acute care hospitals purchased by the Helios
      Hospital Group in Germany from one year before to three years after the start of
      the intervention. In-hospital mortality for myocardial infarction, heart failure,
      ischemic stroke, and pneumonia was stratified by initial hospital performance and
      compared to the German average. Following the intervention, hospitals whose
      performance was initially subpar significantly reduced in-hospital mortality for
      all four diseases. In hospitals that initially performed well, no significant
      changes in mortality were observed. The observational nonrandomized data suggest
      that the quality management approach was associated with improved outcomes in
      initially subpar hospitals. Disease-specific measures of mortality, combined with
      peer reviews, can be used to direct actions to areas of potential improvement.

PMID- 24019368
TI  - No evidence that primary care physicians offer less care to Medicaid, community
      health center, or uninsured patients.
AB  - The Affordable Care Act increases US investment in Medicaid and community health
      centers, yet many people believe that care in such safety-net programs is
      substandard. Using data from more than 31,000 visits to primary care physicians
      in the period 2006-10, we examined whether the length or content of a visit was
      different for safety-net patients-those insured by Medicaid, those who are
      uninsured, and those seen in a community health center-compared to patients with
      private insurance. We found no significant differences in the average length of a
      primary care visit or in the likelihood of a patient's receiving preventive
      health counseling. Medicaid patients received more diagnostic and treatment
      services, and uninsured patients received fewer services, compared to privately
      insured patients, but the differences were small. This analysis indicates that
      length and content of primary care visits are comparable for safety-net and other
      patients. The main factors that contribute to differences in visit length and
      content are patients' health needs and the type of visit involved.

PMID- 24019369
TI  - Minnesota's provider-initiated approach yields care quality gains at
      participating nursing homes.
AB  - Minnesota's Performance-Based Incentive Payment Program uses a collaborative,
      provider-initiated approach to nursing home quality improvement: up-front funding
      of evidence-based projects selected and designed by participating facilities,
      with accountable performance targets. During the first 4 rounds of funding (2007
      10), 66 projects were launched at 174 facilities. Using a composite quality
      measure representing multiple dimensions of clinical care, we found that
      facilities participating during this period exhibited significantly greater gains
      than did nonparticipating facilities, in both targeted areas and overall quality,
      and maintained their quality advantage after project completion. Participating
      and nonparticipating facilities were similar at baseline with respect to quality
      scores and improvement trends, as well as acuity-adjusted payment, operating
      costs, and nurse staffing. Although self-selection precludes firm conclusions
      regarding the program's impacts, early findings indicate that the program shows
      promise for incentivizing nursing home quality improvement, both in facility
      identified areas of concern and overall.

PMID- 24019370
TI  - Health reform in Massachusetts increased adult dental care use, particularly
      among the poor.
AB  - States frequently expand or limit dental benefits for adults covered by Medicaid.
      As part of statewide health reform in 2006, Massachusetts expanded dental
      benefits to all adults ages 19-64 whose annual income was at or below 100 percent
      of the federal poverty level. We examined the impact of this reform and found
      that it led to an increase in dental care use among the Massachusetts adult
      population, driven by gains among poor adults. Compared to the prereform period,
      dental care use increased by 2.9 percentage points among all nonelderly adults in
      Massachusetts, relative to all nonelderly adults in eight control states. For
      poor Massachusetts adults, the effect was larger-an eleven-percentage-point
      increase in dental care use above the increase among the state's nonpoor
      residents. The Massachusetts experience provides evidence that providing dental
      benefits to poor adults through Medicaid can improve dental care access and use.
      Our results imply that the lack of expanded dental coverage for low-income adults
      under the Affordable Care Act is a missed opportunity to improve access to oral
      care.

PMID- 24019372
TI  - New strategies to improve food marketing to children.
AB  - Federal efforts to address the impact of food marketing on children began more
      than thirty years ago, when the Federal Trade Commission sought comment on
      strategies to reduce young children's exposure to food advertising. The food,
      advertising, and television industries mounted a virulent response, and Congress
      withdrew the commission's authority to regulate unfair advertising to children.
      The same industries and Congress responded equally aggressively to the proposed
      nutrition criteria for food products marketed to children drafted by a working
      group of federal agencies in 2011. Although federal efforts over the past thirty
      years have led to modest improvements in food quality and marketing practices,
      commercial interests have consistently overridden the health concerns of
      children. Mobilization of parents as a political force to improve standards for
      food marketed to children, use of social media for counteradvertising, and the
      development of new technologies to decrease exposure to food advertisements could
      reduce the impact of food marketing to children.

PMID- 24019371
TI  - Dentists' partnership of Michigan's Calhoun County: a care model for uninsured
      populations.
AB  - Community leaders in Calhoun County, Michigan, identified access to dental care
      as an acute local need and in early 2007 organized Calhoun County Dentists'
      Partnership. A group of stakeholders developed a program centered on local
      dentists who donated a designated number of office visits per month to care for
      uninsured county residents. Residents enrolled in the program were required to
      attend an oral health class; receive a dental screening, cleaning, and dental x
      rays by a dental hygienist; and complete a designated number of hours of
      community service before seeing a dentist. Since the program's 2007 inception,
      approximately 4,000 people have received dental services valued at approximately
      $510,000. In turn, program participants provided more than 57,000 hours of
      community service. The program is credited with reducing the number of patients
      presenting to a local hospital emergency department for dental pain by 70 percent
      between 2006 and 2012. Similar programs are now under way in thirteen other
      communities in the Midwest, which shows that such local initiatives,
      volunteerism, and community organization can address dental care access needs.

PMID- 24019374
TI  - Against all odds: how a Medicaid waiver brought our critically ill daughter home.

PMID- 24019373
TI  - Proportion of physicians in large group practices continued to grow in 2009-11.
AB  - Payers and advocates for improved health care quality are raising expectations
      for greater care coordination and accountability for care delivery, and physician
      groups may be responding by becoming larger. We used Medicare claims from the
      period 2009-11, merged with information from the Medicare provider enrollment
      database, to measure whether physician group sizes have been increasing over time
      and in association with physician characteristics. All US physicians serving
      Medicare fee-for-service patients in any practice setting were included. The
      percentage of physicians in groups of more than fifty increased from 30.9 percent
      in 2009 to 35.6 percent in 2011. This shift occurred across all specialty
      categories, both sexes, and all age groups, although it was more prominent among
      physicians under age forty than those age sixty or older. The movement of
      physicians into groups is not a new phenomenon, but our data suggest that the
      groups are larger than surveys have previously indicated. Questions for future
      studies include whether there are significant cost savings or quality
      improvements associated with increased practice size.

PMID- 24019375
TI  - Foundation funding to improve health in rural areas.

PMID- 24019376
TI  - Dutch health insurance exchanges.

PMID- 24019377
TI  - Medicare supplemental coverage.

PMID- 24019378
TI  - Medicare supplemental coverage: the authors reply.

PMID- 24019379
TI  - Dutch insurance exchanges: the authors reply.

PMID- 24019380
TI  - Acceptability of conditions in a community-led cash transfer programme for
      orphaned and vulnerable children in Zimbabwe.
AB  - Evidence suggests that a regular and reliable transfer of cash to households with
      orphaned and vulnerable children has a strong and positive effect on child
      outcomes. However, conditional cash transfers are considered by some as
      particularly intrusive and the question on whether or not to apply conditions to
      cash transfers is an issue of controversy. Contributing to policy debates on the
      appropriateness of conditions, this article sets out to investigate the overall
      buy-in of conditions by different stakeholders and to identify pathways that
      contribute to an acceptability of conditions. The article draws on data from a
      cluster-randomized trial of a community-led cash transfer programme in
      Manicaland, eastern Zimbabwe. An endpoint survey distributed to 5167 households
      assessed community members' acceptance of conditions and 35 in-depth interviews
      and 3 focus groups with a total of 58 adults and 4 youth examined local
      perceptions of conditions. The study found a significant and widespread
      acceptance of conditions primarily because they were seen as fair and a proxy for
      good parenting or guardianship. In a socio-economic context where child grants
      are not considered a citizen entitlement, community members and cash transfer
      recipients valued the conditions associated with these grants. The community
      members interpreted the fulfilment of the conditions as a proxy for achievement
      and merit, enabling them to participate rather than sit back as passive
      recipients of aid. Although conditions have a paternalistic undertone and
      engender the sceptics' view of conditions being pernicious and even abominable,
      it is important to recognize that community members, when given the opportunity
      to participate in programme design and implementation, can take advantage of
      conditions and appropriate them in a way that helps them manage change and
      overcome the social divisiveness or conflict that otherwise may arise when some
      people are identified to benefit and others not. 

PMID- 24019381
TI  - Personalizing the treatment of pediatric medulloblastoma: Polo-like kinase 1 as a
      molecular target in high-risk children.
AB  - Medulloblastoma is the most common malignant brain tumor in children. This
      disease is heterogeneous and is composed of four subtypes of medulloblastoma
      [WNT, Sonic Hedgehog (SHH), Group 3, and Group 4]. An immediate goal is to
      identify novel molecular targets for the most aggressive forms of
      medulloblastoma. Polo-like kinase 1 (PLK1) is an oncogenic kinase that controls
      cell cycle and proliferation, making it a strong candidate for medulloblastoma
      treatment. In this study, pediatric medulloblastomas were subtyped in two patient
      cohorts (discovery cohort, n = 63 patients; validation cohort, n = 57 patients)
      using NanoString nCounter analysis and PLK1 mRNA was assessed. We determined that
      the SHH and Group 3 subtypes were independently associated with poor outcomes in
      children as was PLK1 using Cox regression analyses. Furthermore, we screened a
      library of 129 compounds in clinical trials using a model of pediatric
      medulloblastoma and determined that PLK1 inhibitors were the most promising class
      of agents against the growth of medulloblastoma. In patient-derived primary
      medulloblastoma isolates, the PLK1 small-molecule inhibitor BI2536 suppressed the
      self-renewal of cells with high PLK1 but not low PLK1 expression. PLK1 inhibition
      prevented medulloblastoma cell proliferation, self-renewal, cell-cycle
      progression, and induced apoptosis. In contrast, the growth of normal neural stem
      cells was unaffected by BI2536. Finally, BI2536 extended survival in
      medulloblastoma-bearing mice with efficacy comparable with Headstart, a standard
      of-care chemotherapy regimen. We conclude that patients with medulloblastoma
      expressing high levels of PLK1 are at elevated risk. These preclinical studies
      pave the way for improving the treatment of medulloblastoma through PLK1
      inhibition.

PMID- 24019383
TI  - Operating and environmental performances of commercial-scale waste gasification
      and melting technology.
AB  - Gasification technologies for waste processing are receiving increased interest.
      A lot of gasification technologies, including gasification and melting, have been
      developed in Japan and Europe. However, the flue gas and heavy metal behaviors
      have not been widely reported, even though those of grate furnaces have been
      reported. This article reports flue gas components of gasification and melting
      technology in different flue gas treatment systems. Hydrogen chloride
      concentrations at the inlet of the bag filter ranged between 171 and 180 mg Nm(
      3) owing to de-acidification by limestone injection to the gasifier. More than
      97.8% of hydrogen chlorides were removed by a bag filter in both of the flue gas
      treatment systems investigated. Sulfur dioxide concentrations at the inlet of the
      baghouse were 4.8 mg Nm(-3) and 12.7 mg Nm(-3), respectively. Nitrogen oxides are
      highly decomposed by a selective catalytic reduction system. Owing to the low
      regenerations of polychlorinated dibenzo-p-dioxins and furans, and the selective
      catalytic reduction system, the concentrations of polychlorinated dibenzo-p
      dioxins and furans at the stacks were significantly lower without activated
      carbon injection. More than 99% of chlorine is distributed in fly ash. Low
      boiling-point heavy metals, such as lead and zinc, are distributed in fly ash at
      rates of 97.6% and 96.5%, respectively. Most high-boiling-point heavy metals,
      such as iron and copper, are distributed in metal. It is also clarified that the
      slag is stable and contains few harmful heavy metals, such as lead. The heavy
      metal distribution behaviors are almost the same regardless of the compositions
      of the processed waste. These results indicate that the gasification of municipal
      solid waste constitutes an ideal approach to environmental conservation and
      resource recycling. 

PMID- 24019382
TI  - Mutationally activated PIK3CA(H1047R) cooperates with BRAF(V600E) to promote lung
      cancer progression.
AB  - Adenocarcinoma of the lung, a leading cause of cancer death, frequently displays
      mutational activation of the KRAS proto-oncogene but, unlike lung cancers
      expressing mutated EGFR, ROS1, or ALK, there is no pathway-targeted therapy for
      patients with KRAS-mutated lung cancer. In preclinical models, expression of
      oncogenic KRAS(G12D) in the lung epithelium of adult mice initiates development
      of lung adenocarcinoma through activation of downstream signaling pathways. In
      contrast, mutationally activated BRAF(V600E), a KRAS effector, fails to initiate
      lung carcinogenesis despite highly efficient induction of benign lung
      tumorigenesis. To test if phosphoinositide 3-kinase (PI3K)-alpha (PIK3CA),
      another KRAS effector, might cooperate with oncogenic BRAF(V600E) to promote lung
      cancer progression, we used mice carrying a conditional allele of Pik3ca that
      allows conversion of the wild-type catalytic subunit of PIK3CA to mutationally
      activated PIK3CA(H1047R). Although expression of PIK3CA(H1047R) in the lung
      epithelium, either alone or in combination with PTEN silencing, was without
      phenotype, concomitant expression of BRAF(V600E) and PIK3CA(H1047R) led to
      dramatically decreased tumor latency and increased tumor burden compared with
      BRAF(V600E) alone. Most notably, coexpression of BRAF(V600E) and PIK3CA(H1047R)
      elicited lung adenocarcinomas in a manner reminiscent of the effects of
      KRAS(G12D). These data emphasize a role for PI3K signaling, not in lung tumor
      initiation per se, but in both the rate of tumor growth and the propensity of
      benign lung tumors to progress to a malignant phenotype. Finally, biologic and
      biochemical analysis of BRAF(V600E)/PIK3CA(H1047R)-expressing mouse lung cancer
      cells revealed mechanistic clues about cooperative regulation of the cell
      division cycle and apoptosis by these oncogenes.

PMID- 24019384
TI  - Numerical simulation of landfill gas pressure distribution in landfills.
AB  - Landfill gas emissions are recognized as one of the three major concerns in
      municipal solid waste landfills. There are many factors that affect the
      generation of landfill gas when the landfill is capped. In this article, a model
      has been developed based on the theory of porous media flow. The model could
      predict the pressure distribution of landfill gas in landfill, coupling the
      effect of landfill settlement. According to the simulation analysis of landfill,
      it was found that: (a) the landfill gas pressure would reach a peak after 1.5
      years, then begin to decline, and the rate of decay would slow down after 10
      years; (b) the influence radius of the gas wells is limited; (c) the peak value
      of landfill gas pressure is larger, it appears later and the rate of decay is
      slower when the landfill settlement is considered in the model; (d) the
      calculation of excess gas pressure in landfill under different negative pressures
      of the extraction well is compared between this model and another model, and the
      results show that the relative pressure distribution form and range are almost
      the same. 

PMID- 24019385
TI  - Toxicological evaluation of landfill leachate using plant (Allium cepa) and fish
      (Leporinus obtusidens) bioassays.
AB  - The disposal of municipal waste in landfills may pose an environmental problem
      because the product of the decomposition of these residues generates large
      volumes of leachate, which may present high toxicity. The aim of this study was
      to assess the toxic and genotoxic effects of a sample of untreated leachate in
      fish (Leporinus obtusidens) and onions (Allium cepa). The leachate was collected
      in a landfill located in the region of Vale do Rio dos Sinos, southern Brazil.
      The fish were exposed to raw leachate, at concentrations of 0.5%, 1.0%, 5%, 10%
      and 20% for 6 days, while the bulbs of A. cepa were exposed to concentrations of
      5%, 10%, 25%, 50% and 100% for 48 h. For fish, the concentrations of 5%, 10% and
      20% were lethal, thus indicating high toxicity; however, sublethal concentrations
      (0.5% and 1.0%) showed no genotoxicity by micronucleus test when compared with
      the control group. In the bioassays involving onions, high toxicity was observed,
      with significant reduction of root growth and mitotic index in bulbs exposed to
      the 100% concentration of the leachate. An increase in the frequency of
      chromosome abnormalities in the A. cepa root cells in anaphase-telophase was
      observed in accordance with the increase in the concentration of leachate (5%,
      10%, 25% and 50%), with values significantly greater than the control, at the
      highest concentration. The results showed that the leachate contains toxic and
      genotoxic substances, thus representing a major source of environmental pollution
      if not handled properly.

PMID- 24019386
TI  - Choosing wisely: you get what you pay for.
AB  - Choosing Wisely is an initiative of the American Board of Internal Medicine
      Foundation in partnership with Consumer Reports and other consumer-oriented
      organizations to encourage "physicians, patients and other health care
      stakeholders to think and talk about medical tests and procedures that may be
      unnecessary, and in some instances cause harm."(1) The initiative's broader goal
      is to ensure that the right care is delivered at the right time and in the right
      place. As part of the initiative, 9 professional societies in 2012 each released
      "Five things physicians and patients should question." In this issue of
      Neurology(r), Langer-Gould et al.(2) present the American Academy of Neurology's
      list, which joined those of 16 other specialty societies released in February
      2013. 

PMID- 24019387
TI  - Extensive subarachnoid venous angiomatosis with hydrocephalus in phacomatosis
      pigmentovascularis.
AB  - An 8-month-old boy with cutaneous vascular malformations and dermal melanocytosis
      (Mongolian spots, figure, A) on the face and trunk was diagnosed with
      phacomatosis pigmentovascularis type 2. He had normal neurodevelopment, but
      progressive macrocephaly (figure, B). Linear brain ultrasonography showed
      extensive venous angiomatosis in the prominent subarachnoid space (figure, C and
      D). MRI revealed cortical sulcal widening, prominent leptomeningeal vessels in an
      enlarged subarachnoid space (figure, E and F), and communicating hydrocephalus
      (figure, F). Neurologic involvement in phacomatosis pigmentovascularis is
      uncommon except in Sturge-Weber and Klippel-Trenaunay syndromes.(1,2)
      Communicating hydrocephalus due to subarachnoid angiomatosis may be
      underdiagnosed in phacomatosis pigmentovascularis, and should be considered in
      case of progressive macrocephaly. 

PMID- 24019388
TI  - The American Academy of Neurology's top five Choosing Wisely recommendations.

PMID- 24019389
TI  - Clinical reasoning: a 48-year-old woman with progressive spastic-ataxic gait.
AB  - A 48-year-old woman was referred for evaluation of progressive gait ataxia and
      stiffness of both legs over 6 months. 

PMID- 24019390
TI  - Clinical reasoning: a 62-year-old man with right wrist drop.

PMID- 24019391
TI  - Teaching neuroimages: cerebral white matter involvement in a patient with Vogt
      Koyanagi-Harada syndrome.
AB  - A 27-year-old man presented with decreased vision bilaterally. Ophthalmologic
      examination revealed panuveitis with bilateral serous retinal detachments (figure
      1) characteristic of Vogt-Koyanagi-Harada (VKH) syndrome. Analysis of CSF
      revealed mild pleocytosis. No oligoclonal bands were detected. On MRI, there was
      bilateral abnormal thickening of the choroid with retinal detachment (figure 2, A
      and B), with hyperintense lesion on fluid-attenuated inversion recovery (FLAIR)
      image in the periventricular deep white matter (figure 2C). VKH syndrome is one
      of the causes of uveo-meningeal syndromes. Differential diagnosis of VKH syndrome
      includes Wegener granulomatosis, sarcoidosis, and Behcet disease.(1) The main
      disorders showing association with hyperintense plaques on deep white matter
      FLAIR images are inflammatory, metabolic, vascular, degenerative, autoimmune, and
      demyelinating diseases. MRI is a helpful tool in diagnosing VKH syndrome; in
      addition to the typical bilateral ocular findings, scattered periventricular
      white matter lesions on FLAIR are also described.(2.) 

PMID- 24019392
TI  - Teaching NeuroImages: sacral spine chloroma.
AB  - A 23-year-old man with recurrent acute myeloid leukemia (AML) underwent
      successful reinduction and was judged posttherapy to be in complete remission.
      Soon thereafter, he complained of pain in his left buttock radiating into his
      left posterior thigh. Neurologic examination was unremarkable. Radiographic
      evaluation demonstrated a left S2 lesion suggestive of a nerve sheath tumor
      (figure 1). An open biopsy was performed that revealed a chloroma pathologically
      (figure 2), sometimes referred to as a myeloid sarcoma.(1,2) Most chloromas are
      found in patients with recurrent AML and are overwhelmingly intracranial.(1)
      Infrequently, chloromas are paraspinal, and in this location present with
      epidural spinal cord compression.(2) Intraspinal invasion by a chloroma is rare.
      Systemic evaluation confirmed recurrent AML, for which he was successfully
      treated with reinduction and whole-body irradiation followed by an allogeneic
      transplant. He is currently disease-free and neurologically asymptomatic 1 year
      posttransplant. 

PMID- 24019394
TI  - Longitudinal changes in IGF-I and IGFBP-3, and mammographic density among
      postmenopausal women.
AB  - A relation between the breast cancer risk factors, insulin-like growth factor-I
      (IGF-I) and mammographic density, is biologically plausible, but results from
      cross-sectional epidemiologic studies have been mixed. Our objective was to
      examine the relation in a longitudinal manner, that is, between the change in
      circulating IGF-I concentrations and the change in mammographic measures over one
      year. Data from an exercise intervention trial conducted in 302 postmenopausal
      women ages 50 to 74 years were used. Blood drawn at baseline and postintervention
      was assessed for IGF-I and its binding protein (IGFBP-3) by direct
      chemiluminscent immunoassay. Area and volumetric measurements of mammographic
      dense fibroglandular and nondense fatty tissue were made. Statistical analyses
      were based on multiple linear regression. A one SD (20.2 ng/mL) change in IGF-I
      over one year was associated with small changes in percent dense area [mean:
      0.8%; 95% confidence interval (CI), 0.1-1.4] and dense area (mean: 1.2 cm(2); 95%
      CI, 0.2-2.1). Change in IGFBP-3 was also associated with percent and absolute
      dense area. Absolute and percent dense volume, and mammographic measures
      representing fatty tissue (nondense area and volume) were not associated with
      changes in IGF-I and IGFBP-3. Longitudinal associations may be more detectable
      than cross-sectional associations due to the absence of confounding by invariant
      personal factors. Absolute and percent dense area, measures that are related to
      breast cancer risk, may be affected by IGF-I. Confirmation should be sought in
      further longitudinal studies in which larger changes in the IGF system are
      evoked.

PMID- 24019393
TI  - Equol-producing status, isoflavone intake, and breast density in a sample of U.S.
      Chinese women.
AB  - BACKGROUND: Differences in ability to metabolize daidzein to equol might help
      explain inconsistent findings about isoflavones and breast cancer. We examined
      equol-producing status in relation to breast density, a marker of breast cancer
      risk, and evaluated whether an association of isoflavone intake with breast
      density differs by equol-producing status in a sample of Chinese immigrant women.
      METHODS: Participants were 224 women, ages 36 to 58 years, enrolled in a study on
      diet and breast density. All women completed dietary recall interviews, underwent
      a soy challenge to assess equol-producing status, and received a mammogram
      assessed for breast density using a computer-assisted method. RESULTS: In our
      sample, 30% were classified as equol producers. In adjusted linear regression
      models, equol producers had significantly lower mean dense tissue area (32.8 vs.
      37.7 cm(2), P = 0.03) and lower mean percent breast density (32% vs. 35%, P =
      0.03) than nonproducers. Significant inverse associations of isoflavone intake
      with dense area and percent density were apparent, but only in equol producers
      (interaction P = 0.05 for both). CONCLUSIONS: These results support the
      possibility that equol-producing status affects breast density and that effects
      of isoflavones on breast density depend on ability to metabolize daidzein to
      equol. IMPACT: Although these findings warrant confirmation in a larger sample,
      they offer a possible explanation for the inconsistent findings about soy intake
      and breast density and possibly breast cancer risk as well. The findings further
      suggest the importance of identifying factors that influence equol-producing
      status and exploring appropriate targeting of interventions.

PMID- 24019395
TI  - Lack of evidence for human T-lymphotropic virus type 1 and mouse mammary tumor
      like virus involvement in the genesis of childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: In Mexico City, the incidence of childhood acute lymphoblastic
      leukemia (ALL) is one of the highest in the world; epidemiologic evidence
      suggests that infectious agents could be involved in the genesis of this disease.
      Early transmitted oncogenic retroviruses infecting lymphocytes are important
      candidates. METHODS: PCR-based assays were used to screen viral genomic sequences
      of human T-cell lymphotrophic virus, type 1 (HTLV1) and mouse mammary tumor virus
      (MMTV)-like virus (MMTV-LV) in leukemic cells from 67 pediatric patients with
      ALL. RESULTS: Viral genomic sequences were not detected in any sample by neither
      standard nor nested PCR. CONCLUSIONS: Because of the methodologic strictness and
      high statistical power of the study, these results suggest that HTLV1 and MMTV-LV
      are not involved in the genesis of childhood ALL in Mexican children. IMPACT: To
      our knowledge, this is the first work exploring the direct participation of HTLV1
      and MMTV-LV retroviruses in childhood ALL development.

PMID- 24019397
TI  - CYP2C19 poor metabolizer is associated with clinical outcome of clopidogrel
      therapy in acute myocardial infarction but not stable angina.
AB  - BACKGROUND: More intensive platelet suppression is required in patients with
      acute myocardial infarction (AMI) than in those with stable angina because of
      differential platelet activation between AMI and stable angina. In this context,
      CYP2C19 genotype leading to reduced active metabolite formation may profoundly
      affect the clinical outcome of clopidogrel therapy in patients with AMI compared
      with those with stable angina. METHODS AND RESULTS: Effects of CYP2C19 genotypes
      on the clinical outcome of clopidogrel therapy were evaluated in 2188 patients
      (532 patients with AMI and 1656 patients with stable angina) undergoing
      percutaneous coronary intervention. The primary clinical outcome was a composite
      of major adverse cardiac and cerebrovascular events defined as death from any
      cause, nonfatal myocardial infarction, or stroke during 1 year of clopidogrel
      therapy. Compared with extensive metabolizer, the CYP2C19 poor metabolizer was
      significantly associated with higher risk of major adverse cardiac and
      cerebrovascular events in patients with AMI (hazard ratio, 2.88; 95% confidence
      interval, 1.27-6.53; P=0.011). However, this finding was not seen in patients
      with stable angina. A significant interaction between CYP2C19 genotypes and
      disease subsets of AMI and stable angina was identified with respect to major
      adverse cardiac and cerebrovascular events (adjusted interaction P=0.045). The
      patients with AMI showed lower percent inhibition of P2Y12 compared with patients
      with stable angina in CYP2C19 poor metabolizer or CYP2C19 intermediate
      metabolizer genotype groups but not in CYP2C19 extensive metabolizer genotype
      group. CONCLUSIONS: CYP2C19 poor metabolizer is associated with poor clinical
      outcome of clopidogrel therapy in Asian patients with AMI but not in those with
      stable angina possibly because of differential requirement of platelet
      suppression in patients with AMI and stable angina. CLINICAL TRIAL REGISTRATION
      INFORMATION: URL: clinicaltrials.gov. Identifier: NCTO1239914.

PMID- 24019396
TI  - Telomere length varies by DNA extraction method: implications for epidemiologic
      research.
AB  - BACKGROUND: Both shorter and longer telomeres in peripheral blood leukocyte (PBL)
      DNA have been associated with cancer risk. However, associations remain
      inconsistent across studies of the same cancer type. This study compares DNA
      preparation methods to determine telomere length from patients with colorectal
      cancer. METHODS: We examined PBL relative telomere length (RTL) measured by
      quantitative PCR (qPCR) in 1,033 patients with colorectal cancer and 2,952
      healthy controls. DNA was extracted with phenol/chloroform, PureGene, or QIAamp.
      RESULTS: We observed differences in RTL depending on DNA extraction method (P <
      0.001). Phenol/chloroform-extracted DNA had a mean RTL (T/S ratio) of 0.78 (range
      0.01-6.54) compared with PureGene-extracted DNA (mean RTL of 0.75; range 0.00
      12.33). DNA extracted by QIAamp yielded a mean RTL of 0.38 (range 0.02-3.69). We
      subsequently compared RTL measured by qPCR from an independent set of 20
      colorectal cancer cases and 24 normal controls in PBL DNA extracted by each of
      the three extraction methods. The range of RTL measured by qPCR from QIAamp
      extracted DNA (0.17-0.58) was less than from either PureGene or phenol/chloroform
      (ranges, 0.04-2.67 and 0.32-2.81, respectively). CONCLUSIONS: RTL measured by
      qPCR from QIAamp-extracted DNA was less than from either PureGene or
      phenol/chloroform (P < 0.001). IMPACT: Differences in DNA extraction method may
      contribute to the discrepancies between studies seeking to find an association
      between the risk of cancer or other diseases and RTL.

PMID- 24019398
TI  - Novel gastro-renal axis and sodium regulation during hypertension.

PMID- 24019400
TI  - Dietary salt intake regulates WNK3-SPAK-NKCC1 phosphorylation cascade in mouse
      aorta through angiotensin II.
AB  - Na-K-Cl cotransporter isoform 1 (NKCC1) is involved in the regulation of vascular
      smooth muscle cell contraction. Recently, the with-no-lysine kinase (WNK)
      STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NKCC1 phosphorylation
      cascade in vascular smooth muscle cells was found to be important in the
      regulation of vascular tone. In this study, we investigated whether the WNK-SPAK
      NKCC1 cascade in mouse aortic tissue is regulated by dietary salt intake and the
      mechanisms responsible. Phosphorylation of SPAK and NKCC1 was significantly
      reduced in the aorta in high-salt-fed mice and was increased in the aorta in low
      salt-fed mice, indicating that the WNK-SPAK-NKCC1 phosphorylation cascade in the
      aorta was indeed regulated by dietary salt intake. Acute and chronic angiotensin
      II infusion increased phosphorylation of SPAK and NKCC1 in the mouse aorta. In
      addition, valsartan, an antagonist of angiotensin II type 1 receptor, inhibited
      low-salt diet-induced phosphorylation of SPAK and NKCC1, demonstrating that
      angiotensin II activates the WNK-SPAK-NKCC1 phosphorylation cascade through the
      angiotensin II type 1 receptor. However, a low-salt diet and angiotensin II
      together did not increase phosphorylation of SPAK and NKCC1 in the aorta in WNK3
      knockout mice, indicating that activation of the WNK-SPAK-NKCC1 phosphorylation
      cascade induced by a low-salt diet and angiotensin II is dependent on WNK3.
      Indeed, angiotensin II-induced increases in blood pressure were diminished in
      WNK3 knockout mice. In addition, decreased response to angiotensin II in the
      mesenteric arteries was observed in WNK3 knockout mice. Our data also clarified a
      novel mechanism for regulation of vascular tonus by angiotensin II. Inhibition of
      this cascade could, therefore, be a novel therapeutic target in hypertension. 

PMID- 24019399
TI  - Gastrin and D1 dopamine receptor interact to induce natriuresis and diuresis.
AB  - Oral NaCl produces a greater natriuresis and diuresis than the intravenous
      infusion of the same amount of NaCl. Gastrin is the major gastrointestinal
      hormone taken up by renal proximal tubule (RPT) cells. We hypothesized that renal
      gastrin and dopamine receptors interact to synergistically increase sodium
      excretion, an impaired interaction of which may be involved in the pathogenesis
      of hypertension. In Wistar-Kyoto rats, infusion of gastrin induced natriuresis
      and diuresis, which was abrogated in the presence of a gastrin (cholecystokinin B
      receptor [CCKBR]; CI-988) or a D1-like receptor antagonist (SCH23390). Similarly,
      the natriuretic and diuretic effects of fenoldopam, a D1-like receptor agonist,
      were blocked by SCH23390, as well as by CI-988. However, the natriuretic effects
      of gastrin and fenoldopam were not observed in spontaneously hypertensive rats.
      The gastrin/D1-like receptor interaction was also confirmed in RPT cells. In RPT
      cells from Wistar-Kyoto but not spontaneously hypertensive rats, stimulation of
      either D1-like receptor or gastrin receptor inhibited Na(+)-K(+)-ATPase activity,
      an effect that was blocked in the presence of SCH23390 or CI-988. In RPT cells
      from Wistar-Kyoto and spontaneously hypertensive rats, CCKBR and D1 receptor
      coimmunoprecipitated, which was increased after stimulation of either D1 receptor
      or CCKBR in RPT cells from Wistar-Kyoto rats; stimulation of one receptor
      increased the RPT cell membrane expression of the other receptor, effects that
      were not observed in spontaneously hypertensive rats. These data suggest that
      there is a synergism between CCKBR and D1-like receptors to increase sodium
      excretion. An aberrant interaction between the renal CCK BR and D1-like receptors
      (eg, D1 receptor) may play a role in the pathogenesis of hypertension. 

PMID- 24019401
TI  - Kidney hypoxia, attributable to increased oxygen consumption, induces nephropathy
      independently of hyperglycemia and oxidative stress.
AB  - Diabetic nephropathy is strongly associated with both increased oxidative stress
      and kidney tissue hypoxia. The increased oxidative stress causes increased kidney
      oxygen consumption resulting in kidney tissue hypoxia. To date, it has been
      difficult to determine the role of kidney hypoxia, per se, for the development of
      nephropathy. We tested the hypothesis that kidney hypoxia, without confounding
      factors such as hyperglycemia or elevated oxidative stress, results in
      nephropathy. To induce kidney hypoxia, dinitrophenol (30 mg per day per kg
      bodyweight by gavage), a mitochondrial uncoupler that increases oxygen
      consumption and causes kidney hypoxia, was administered for 30 consecutive days
      to rats. Thereafter, glomerular filtration rate, renal blood flow, kidney oxygen
      consumption, kidney oxygen tension, kidney concentrations of glucose and
      glycogen, markers of oxidative stress, urinary protein excretion, and
      histological findings were determined and compared with vehicle-treated controls.
      Dinitrophenol did not affect arterial blood pressure, renal blood flow,
      glomerular filtration rate, blood glucose, or markers of oxidative stress but
      increased kidney oxygen consumption, and reduced cortical and medullary
      concentrations of glucose and glycogen, and resulted in intrarenal tissue
      hypoxia. Furthermore, dinitrophenol treatment increased urinary protein
      excretion, kidney vimentin expression, and infiltration of inflammatory cells. In
      conclusion, increased mitochondrial oxygen consumption results in kidney hypoxia
      and subsequent nephropathy. Importantly, these results demonstrate that kidney
      tissue hypoxia, per se, without confounding hyperglycemia or oxidative stress,
      may be sufficient to initiate the development of nephropathy and therefore
      demonstrate a new interventional target for treating kidney disease. 

PMID- 24019402
TI  - Concerns for the heart failure reduction in the NAGOYA HEART Study based on meta
      regression from the evidence.

PMID- 24019403
TI  - Target sequencing, cell experiments, and a population study establish endothelial
      nitric oxide synthase (eNOS) gene as hypertension susceptibility gene.
AB  - A case-control study revealed association between hypertension and rs3918226 in
      the endothelial nitric oxide synthase (eNOS) gene promoter (minor/major allele,
      T/C allele). We aimed at substantiating these preliminary findings by target
      sequencing, cell experiments, and a population study. We sequenced the 140-kb
      genomic area encompassing the eNOS gene. In HeLa and HEK293T cells transfected
      with the eNOS promoter carrying either the T or the C allele, we quantified
      transcription by luciferase assay. In 2722 randomly recruited Europeans (53.0%
      women; mean age 40.1 years), we studied blood pressure change and incidence of
      hypertension in relation to rs3918226, using multivariable-adjusted models.
      Sequencing confirmed rs3918226, a binding site of E-twenty six transcription
      factors, as the single nucleotide polymorphism most closely associated with
      hypertension. In T compared with C transfected cells, eNOS promoter activity was
      from 20% to 40% (P<0.01) lower. In the population, systolic/diastolic blood
      pressure increased over 7.6 years (median) by 9.7/6.8 mm Hg in 28 TT homozygotes
      and by 3.8/1.9 mm Hg in 2694 C allele carriers (P<=0.0004). The blood pressure
      rise was 5.9 mm Hg systolic (confidence interval [CI], 0.6-11.1; P=0.028) and 4.8
      mm Hg diastolic (CI, 1.5-8.2; P=0.0046) greater in TT homozygotes, with no
      differences between the CT and CC genotypes (P>=0.90). Among 2013 participants
      normotensive at baseline, 692 (34.4%) developed hypertension. The hazard ratio
      and attributable risk associated with TT homozygosity were 2.04 (CI, 1.24-3.37;
      P=0.0054) and 51.0%, respectively. In conclusion, rs3918226 in the eNOS promoter
      tags a hypertension susceptibility locus, TT homozygosity being associated with
      lesser transcription and higher risk of hypertension. 

PMID- 24019404
TI  - Initiation and progression of chronic kidney disease: can we definitively test
      the chronic hypoxia hypothesis?

PMID- 24019405
TI  - Changes in retinal microvascular caliber precede the clinical onset of
      preeclampsia.
AB  - Preeclampsia is a leading cause of maternal morbidity and mortality. The degree
      of maternal cardiovascular dysfunction that precedes the onset of preeclampsia is
      largely unknown. This prospective cohort study aimed to characterize differences
      in vivo in retinal microvascular caliber and blood pressure throughout pregnancy
      in relation to preeclampsia development. Women were recruited from Royal Prince
      Alfred Hospital, Sydney, Australia, of which 92 women were included in the study.
      Retinal images and blood pressures were collected at 13, 19, 29, and 38 weeks of
      gestation. Retinal vessels were analyzed as the central retinal arteriolar
      equivalent corrected for mean arterial blood pressure and the central retinal
      venular equivalent corrected for mean arterial blood pressure, using generalized
      linear models adjusted for age and body mass index. The preeclampsia group were
      significantly older (P=0.002) and had a significantly higher mean body mass index
      (P=0.005). The central retinal arteriolar equivalent corrected for mean arterial
      blood pressure was significantly reduced at 13 (P=0.03), 19 (P=0.007), and 38
      (P=0.03) weeks of gestation in the preeclampsia group. The central retinal
      venular equivalent corrected for mean arterial blood pressure was also
      significantly lower at 13 (P=0.04) and 19 (P=0.001) weeks of gestation in the
      women who progressed to preeclampsia. This study directly documents increased
      peripheral resistance in vivo, observed as the combination of constricted retinal
      arterioles or venules and elevated blood pressure, in women who later developed
      preeclampsia. This difference preceded the clinical signs of preeclampsia. 

PMID- 24019406
TI  - Subpopulation of proepicardial cells is derived from the somatic mesoderm in the
      chick embryo.
AB  - RATIONALE: The proepicardium (PE) is a transient structure forming at the venous
      pole of the heart and gives rise to the epicardium, fibroblasts, and smooth
      muscle cells. The embryological origin of the PE is presently unclear.
      Asymmetrical formation of the PE on the right inflow tract is a conserved feature
      of many vertebrate embryos, and in the chicken is under the control of fibroblast
      growth factor 8 and snail homolog 1. OBJECTIVE: To gain further insight into the
      process of asymmetrical PE formation, we studied the role of TWIST1 during PE
      formation in the chick embryo. METHODS AND RESULTS: TWIST1 is asymmetrically
      expressed on the right side in the somatic mesoderm under the control of snail
      homolog 1. Fate mapping experiments revealed a contribution of the somatic
      mesoderm to the PE. After colonization of the heart, this cell lineage gives rise
      to the epicardium, smooth muscle cells, and potentially fibroblast. Suppression
      of TWIST1 function in the right coelomic cavity caused a severe disruption of the
      villous protrusions of the PE and Wilms tumor 1 and transcription factor 21
      expression. Rescue with the corresponding mouse cDNA normalized gene expression
      and PE morphology. Forced expression of TWIST1 on the left side induced ectopic
      expression domains of Wilms tumor 1 and transcription factor 21. CONCLUSIONS: A
      significant proportion of the PE has its origin outside of the currently proposed
      domain in the splanchnic layer of the lateral plate mesoderm. The phenotype in
      embryos subjected to TWIST1 loss- or gain-of-function suggests an important
      contribution of somatic mesoderm to the mesothelial cell layer of the PE.

PMID- 24019409
TI  - Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic
      encephalopathy.
AB  - OBJECTIVE: To determine whether antepartum factors alone, intrapartum factors
      alone, or both in combination, are associated with term neonatal hypoxic-ischemic
      encephalopathy (HIE). METHODS: A total of 405 infants >= 35 weeks' gestation with
      early encephalopathy, born between 1992 and 2007, were compared with 239
      neurologically normal infants born between 1996 and 1997. All cases met criteria
      for perinatal asphyxia, had neuroimaging findings consistent with acute hypoxia
      ischemia, and had no evidence for a non-hypoxic-ischemic cause of their
      encephalopathy. RESULTS: Both antepartum and intrapartum factors were associated
      with the development of HIE on univariate analysis. Case infants were more often
      delivered by emergency cesarean delivery (CD; 50% vs 11%, P < .001) and none was
      delivered by elective CD (vs 10% of controls). On logistic regression analysis
      only 1 antepartum factor (gestation >= 41 weeks) and 7 intrapartum factors
      (prolonged membrane rupture, abnormal cardiotocography, thick meconium, sentinel
      event, shoulder dystocia, tight nuchal cord, failed vacuum) remained
      independently associated with HIE (area under the curve 0.88; confidence interval
      0.85-0.91; P < .001). Overall, 6.7% of cases and 43.5% of controls had only
      antepartum factors; 20% of cases and 5.8% of controls had only intrapartum
      factors; 69.5% of cases and 31% of controls had antepartum and intrapartum
      factors; and 3.7% of cases and 19.7% of controls had no identifiable risk factors
      (P < .001). CONCLUSIONS: Our results do not support the hypothesis that HIE is
      attributable to antepartum factors alone, but they strongly point to the
      intrapartum period as the necessary factor in the development of this condition.

PMID- 24019408
TI  - Characterization and identification of a novel candidate vaccine protein through
      systematic analysis of extracellular proteins of Erysipelothrix rhusiopathiae.
AB  - Erysipelothrix rhusiopathiae, the causative agent of swine erysipelas, is a
      facultative intracellular Gram-positive bacterium. It has been shown that animals
      immunized with a filtrate from E. rhusiopathiae cultures are protected against
      lethal challenge. In this study, we identified and characterized the
      extracellular proteins of E. rhusiopathiae to search for novel vaccine antigens.
      A concentrated culture supernatant from the E. rhusiopathiae Fujisawa strain,
      which has been found to induce protection in mice, was analyzed using two
      dimensional electrophoresis. From more than 40 confirmed protein spots, 16 major
      protein spots were selected and subjected to N-terminal amino acid sequence
      determination, and 14 protein spots were successfully identified. The identified
      proteins included housekeeping proteins and other metabolic enzymes. We searched
      for surface-localized proteins by analyzing the genomes of two E. rhusiopathiae
      strains: Fujisawa and ATCC 19414. Genome analysis revealed that the ATCC 19414
      strain has three putative surface-exposed choline-binding proteins (CBPs): CbpA,
      CbpB, and CbpC. Each CBP contains a putative choline-binding domain. The CbpC
      gene is mutated in Fujisawa, becoming a nonfunctional pseudogene. Immunogold
      electron microscopy confirmed that CbpA and CbpB, as well as the majority of the
      metabolic enzymes examined, are associated with the cell surface of E.
      rhusiopathiae Fujisawa. Immunization with recombinant CbpB, but not with other
      recombinant CBPs or metabolic enzymes, protected mice against lethal challenge. A
      phagocytosis assay revealed that antiserum against CbpB promoted opsonin-mediated
      phagocytosis by murine macrophages in vitro. The protective capabilities of CbpB
      were confirmed in pigs, suggesting that CbpB could be used as a vaccine antigen. 

PMID- 24019407
TI  - Novel determinants of intestinal colonization of Salmonella enterica serotype
      typhimurium identified in bovine enteric infection.
AB  - Cattle are naturally infected with Salmonella enterica serotype Typhimurium and
      exhibit pathological features of enteric salmonellosis that closely resemble
      those in humans. Cattle are the most relevant model of gastrointestinal disease
      resulting from nontyphoidal Salmonella infection in an animal with an intact
      microbiota. We utilized this model to screen a library of targeted single-gene
      deletion mutants to identify novel genes of Salmonella Typhimurium required for
      survival during enteric infection. Fifty-four candidate mutants were strongly
      selected, including numerous mutations in genes known to be important for
      gastrointestinal survival of salmonellae. Three genes with previously unproven
      phenotypes in gastrointestinal infection were tested in bovine ligated ileal
      loops. Two of these mutants, STM3602 and STM3846, recapitulated the phenotype
      observed in the mutant pool. Complementation experiments successfully reversed
      the observed phenotypes, directly linking these genes to the colonization defects
      of the corresponding mutant strains. STM3602 encodes a putative transcriptional
      regulator that may be involved in phosphonate utilization, and STM3846 encodes a
      retron reverse transcriptase that produces a unique RNA-DNA hybrid molecule
      called multicopy single-stranded DNA. The genes identified in this study
      represent an exciting new class of virulence determinants for further mechanistic
      study to elucidate the strategies employed by Salmonella to survive within the
      small intestines of cattle. 

PMID- 24019410
TI  - Developmental trajectories of daily activities in children and adolescents with
      cerebral palsy.
AB  - OBJECTIVES: To describe the developmental trajectories of mobility performance
      and daily activities in children and young adults with cerebral palsy (CP). To
      explore the influence of gross motor function and intellectual disability on
      these trajectories. METHODS: Four hundred and twenty-four Dutch participants with
      CP (aged 1-20 years at study onset) were followed yearly over a period of 2 to 4
      years. Developmental trajectories (from ages 1-16 years) were described for
      mobility performance and performance of daily activities, assessed by using the
      Vineland Adaptive Behavior Scale for gross motor function (classified by the
      Gross Motor Function Classification System) and intellectual disability (by IQ or
      school type). A subanalysis was done for performance of daily activities in a
      subgroup of participants without intellectual disability (aged 1-24 years).
      RESULTS: The developmental trajectories of mobility performance differed
      according to levels of gross motor function but not levels of intellectual
      disability. Intellectual disability affected the performance of daily activities,
      with lower overall trajectory levels for participants with intellectual
      disabilities. For participants without intellectual disability, high-level
      developmental trajectories were found, with values similar to those of typically
      developing children despite differences in gross motor function level.
      CONCLUSIONS: Mobility performance is determined mainly by levels of gross motor
      function. For performance of daily activities, intellectual disability was a more
      important determinant. Participants without intellectual disability showed
      developmental trajectories approaching values for typically developing
      participants. These estimated trajectories can guide rehabilitation interventions
      and future expectations for children and young adults with CP.

PMID- 24019411
TI  - First clinical description of an infant with interleukin-36-receptor antagonist
      deficiency successfully treated with anakinra.
AB  - YM is the first son of Tunisian consanguineous parents who developed, at 2 weeks
      of life, an erythematous and scaly eruption, with subsequent rapid evolution
      toward generalized pustular psoriasis. Afterward, cutaneous flares of diffuse
      erythematous rash and pustules involving the whole body appeared, with a once
      weekly periodicity. Intense irritability was present during flares without fever.
      Moreover, since 1 month of age the infant presented with diarrhea, dysphagia, and
      reduced feeding rate, with failure to thrive. Laboratory tests during acute
      flares showed marked leukocytosis, thrombocytosis, and anemia without C-reactive
      protein elevation. Skin biopsy and clinical presentation were consistent with
      pustular psoriasis; nevertheless, the patient did not respond to high-potency
      topical corticosteroids and retinoid acid. As the patient presented with repeated
      skin flares early after birth, as well as serious constitutional distress with
      failure to thrive, an autoinflammatory syndrome like interleukine-1-receptor
      antagonist deficiency or interleukin-36-receptor antagonist deficiency (DITRA)
      was considered. The hypothesis was reinforced by parental consanguinity, and
      absence of skin lesion improvement under standard topical treatment. Genetic
      analyses showed a homozygous mutation in the IL36RN gene (L27P), which represents
      the same mutation recently described in DITRA patients. At age 6 months we
      started treatment with the recombinant interleukin-1 receptor antagonist anakinra
      with efficacy both on constitutional symptoms and skin involvement. DITRA is a
      recently described autoinflammatory disease characterized by repeated flares of
      generalized pustular psoriasis, high fever, asthenia, and systemic inflammation.
      We report herein the first exhaustive clinical description of an infant with
      DITRA who was successfully treated with anakinra. 

PMID- 24019412
TI  - Prevalence of fetal alcohol spectrum disorders in child care settings: a meta
      analysis.
AB  - BACKGROUND: Children often enter a child-care system (eg, orphanage, foster care,
      child welfare system) because of unfavorable circumstances (eg, maternal alcohol
      and/or drug problems, child abuse/neglect). Such circumstances increase the odds
      of prenatal alcohol exposure, and thus this population can be regarded as high
      risk for fetal alcohol spectrum disorders (FASD). The primary objective was to
      estimate a pooled prevalence for fetal alcohol syndrome (FAS) and FASD in various
      child-care systems based on data from existing studies that used an active case
      ascertainment method. METHODS: A systematic literature review, using multiple
      electronic bibliographic databases, and meta-analysis of internationally
      published and unpublished studies that reported the prevalence of FAS and/or FASD
      in all types of child-care systems were conducted. The pooled prevalence
      estimates and 95% confidence intervals (CIs) were calculated by using the Mantel
      Haenszel method, assuming a random effects model. Sensitivity analyses were
      performed for studies that used either passive surveillance or mixed methods.
      RESULTS: On the basis of studies that used active case ascertainment, the overall
      pooled prevalence of FAS and FASD among children and youth in the care of a child
      care system was calculated to be 6.0% (60 per 1000; 95% CI: 38 to 85 per 1000)
      and 16.9% (169 per 1000; 95% CI: 109 to 238 per 1000), respectively. CONCLUSIONS:
      The results confirm that children and youth housed in or under the guardianship
      of the wide range of child-care systems constitute a population that is high-risk
      for FASD. It is imperative that screening be implemented in these at-risk
      populations.

PMID- 24019413
TI  - Validity of different pediatric early warning scores in the emergency department.
AB  - OBJECTIVE: Pediatric early warning scores (PEWS) are being advocated for use in
      the emergency department (ED). The goal of this study was to compare the validity
      of different PEWS in a pediatric ED. METHODS: Ten different PEWS were evaluated
      in a large prospective cohort. We included children aged <16 years who had
      presented to the ED of a university hospital in The Netherlands (2009-2012). The
      validity of the PEWS for predicting ICU admission or hospitalization was
      expressed by the area under the receiver operating characteristic (ROC) curves.
      RESULTS: These PEWS were validated in 17 943 children. Two percent of these
      children were admitted to the ICU, and 16% were hospitalized. The areas under the
      ROC curves for predicting ICU admission, ranging from 0.60 (95% confidence
      interval [CI]: 0.57-0.62) to 0.82 (95% CI: 0.79-0.85), were moderate to good. The
      area under the ROC curves for predicting hospitalization was poor to moderate
      (range: 0.56 [95% CI: 0.55-0.58] to 0.68 [95% CI: 0.66-0.69]). The sensitivity
      and specificity derived from the ROC curves ranged widely for both ICU admission
      (sensitivity: 61.3%-94.4%; specificity: 25.2%-86.7%) and hospital admission
      (sensitivity: 36.4%-85.7%; specificity: 27.1%-90.5%). None of the PEWS had a high
      sensitivity as well as a high specificity. CONCLUSIONS: PEWS can be used to
      detect children presenting to the ED who are in need of an ICU admission. Scoring
      systems, wherein the parameters are summed to a numeric value, were better able
      to identify patients at risk than triggering systems, which need 1 positive
      parameter.

PMID- 24019414
TI  - Risk of suicide attempt in adopted and nonadopted offspring.
AB  - OBJECTIVE: We asked whether adoption status represented a risk of suicide attempt
      for adopted and nonadopted offspring living in the United States. We also
      examined whether factors known to be associated with suicidal behavior would
      mediate the relationship between adoption status and suicide attempt. METHODS:
      Participants were drawn from the Sibling Interaction and Behavior Study, which
      included 692 adopted and 540 nonadopted offspring and was conducted at the
      University of Minnesota from 1998 to 2008. Adoptees were systematically
      ascertained from records of 3 large Minnesota adoption agencies; nonadoptees were
      ascertained from Minnesota birth records. Outcome measures were attempted
      suicide, reported by parent or offspring, and factors known to be associated with
      suicidal behavior including psychiatric disorder symptoms, personality traits,
      family environment, and academic disengagement. RESULTS: The odds of a reported
      suicide attempt were ~4 times greater in adoptees compared with nonadoptees (odds
      ratio: 4.23). After adjustment for factors associated with suicidal behavior, the
      odds of reporting a suicide attempt were reduced but remained significantly
      elevated (odds ratio: 3.70). CONCLUSIONS: The odds for reported suicide attempt
      are elevated in individuals who are adopted relative to those who are not
      adopted. The relationship between adoption status and suicide attempt is
      partially mediated by factors known to be associated with suicidal behavior.
      Continued study of the risk of suicide attempt in adopted offspring may inform
      the larger investigation of suicidality in all adolescents and young adults.

PMID- 24019416
TI  - The rising incidence of celiac disease in Scotland.
AB  - BACKGROUND AND OBJECTIVES: Although the incidence of pediatric celiac disease
      (CD) is increasing globally, it is uncertain whether this is attributed to
      improved case ascertainment or signifies a true rise. We aimed to identify all
      incident cases of childhood CD in southeast Scotland over the period 1990 to 2009
      to assess trends in total incidence and cases diagnosed as a result of (1) a
      classic presentation, (2) a nonclassic presentation, or (3) targeted screening.
      METHODS: Twenty-year retrospective cohort study of case notes, pathology
      databases, endoscopy, and patient records for all children (<16 years of age)
      diagnosed with CD on biopsy in southeast Scotland (at-risk population of 225000
      233000). Data were age-gender standardized and Poisson regression models used to
      calculate changes in incidence over time. RESULTS: A total of 266 children were
      diagnosed from 1990 to 2009 with an increase in incidence from 1.8/100000 (95%
      confidence interval [CI] 1.1-2.7) to 11.7/100000 (95% CI 9.8-13.9) between the
      epochs 1990 to 1994 and 2005 to 2009, respectively (P < .0001). The incidence of
      nonclassic presentation (children with a monosymptomatic presentation and those
      with extraintestinal symptoms) and actively screened cases increased by 1566% (P
      < .05) and 1170% (P < .001) from 1990 to 1999 to 2000 to 2009, respectively.
      However, a rise in the incidence of Oslo classic cases from 1.51/100000 (95% CI
      0.91-2.38) in 1990 to 1994 to 5.22/100000 (95% CI 3.98-6.75) in 2005 to 2009 (P <
      .01) remained evident. CONCLUSIONS: The incidence of pediatric CD increased 6.4
      fold over the 20 years. This study demonstrates that this rise is significant for
      classic CD, indicating a true rise in the incidence of pediatric CD.

PMID- 24019417
TI  - Clinical characteristics of pediatric myasthenia: a surveillance study.
AB  - OBJECTIVE: To evaluate the incidence, clinical features, diagnostic, and
      treatment trends of pediatric myasthenia in Canada. METHODS: Through established
      Canadian Pediatric Surveillance Program methodology, physicians were anonymously
      surveyed for cases of pediatric myasthenia using a standardized clinical
      questionnaire containing deidentified data. Inclusion criteria were any child <18
      years old with >=1 of the following: (1) fluctuating ptosis or extraocular
      weakness, (2) skeletal muscle weakness or fatigue, and (3) any of the following
      supportive tests: clinical response to acetylcholinesterase inhibitor, positive
      antibodies, abnormal slow repetitive nerve stimulation, or single-fiber
      electromyography. RESULTS: In 2 years of surveillance, 57 confirmed cases were
      reported. There were 34 generalized and 18 ocular reports of juvenile myasthenia
      gravis plus 5 congenital myasthenic syndrome cases. There were 14 incident cases
      in 2010 and 6 in 2011. Age of onset ranged from "birth" to 17 years for the
      generalized form compared with 18 months to 11 years for the ocular subtype.
      Positive acetylcholine receptor titers were found in 22 (67%) of 33 generalized
      cases and 8 (44%) of 18 ocular patients. Of patients started on pyridostigmine,
      improvement was noted in 33 (100%) of 33 generalized cases and 15 (88%) of 17
      ocular cases. CONCLUSIONS: This study represents the largest descriptive series
      of pediatric myasthenia in North America and provides valuable information about
      clinical characteristics. A high index of suspicion is important for this
      treatable disease. Children generally respond promptly to readily available
      therapies.

PMID- 24019418
TI  - Eating disorders in adolescents with a history of obesity.
AB  - Adolescent patients with obesity are at significant risk of developing an eating
      disorder (ED), yet due to their higher weight status their symptoms often go
      unrecognized and untreated. Although not widely known, individuals with a weight
      history in the overweight (BMI-for-age >=85th percentile but <95th percentile, as
      defined by Centers for Disease Control and Prevention growth charts) or obese
      (BMI-for-age >=95th percentile, as defined by the Centers for Disease Control and
      Prevention growth charts) range, represent a substantial portion of adolescents
      presenting for ED treatment. Given research that suggests that early intervention
      promotes the best chance of recovery, it is imperative that these children's and
      adolescents' ED symptoms are identified and that intervention is offered before
      the disease progresses. This report presents 2 examples of EDs that developed in
      the context of obese adolescents' efforts to reduce their weight. Each case shows
      specific challenges in the identification of ED behaviors in adolescents with
      this weight history and the corresponding delay such teenagers experience
      accessing appropriate treatment. 

PMID- 24019415
TI  - Cerebral palsy and growth failure at 6 to 7 years.
AB  - OBJECTIVE: To evaluate the association between severity of cerebral palsy (CP)
      and growth to 6 to 7 years of age among children with moderate to severe
      (Mod/Sev) hypoxic ischemic encephalopathy (HIE). It was hypothesized that
      children with Mod/Sev CP would have poorer growth, lower cognitive scores, and
      increased rehospitalization rates compared with children with no CP (No CP).
      METHODS: Among 115 of 122 surviving children followed in the hypothermia trial
      for neonatal HIE, growth parameters and neurodevelopmental status at 18 to 22
      months and 6 to 7 years were available. Group comparisons (Mod/Sev CP and No CP)
      with unadjusted and adjusted analyses for growth <10th percentile and z scores by
      using Fisher's exact tests and regression modeling were conducted. RESULTS:
      Children with Mod/Sev CP had high rates of slow growth and cognitive and motor
      impairment and rehospitalizations at 18 to 22 months and 6 to 7 years. At 6 to 7
      years of age, children with Mod/Sev CP had increased rates of growth parameters
      <10th percentile compared with those with No CP (weight, 57% vs 3%; height, 70%
      vs 2%; and head circumference, 82% vs 13%; P < .0001). Increasing severity of
      slow growth was associated with increasing age (P < .04 for weight, P < .001 for
      length, and P < .0001 for head circumference). Gastrostomy feeds were associated
      with better growth. CONCLUSIONS: Term children with HIE who develop Mod/Sev CP
      have high and increasing rates of growth <10th percentile by 6 to 7 years of age.
      These findings support the need for close medical and nutrition management of
      children with HIE who develop CP.

PMID- 24019419
TI  - Regional implementation of a pediatric cardiology chest pain guideline using
      SCAMPs methodology.
AB  - BACKGROUND AND OBJECTIVES: Chest pain is a complaint for which children are
      frequently evaluated. Cardiac causes are rarely found despite expenditure of
      considerable time and resources. We describe validation throughout New England of
      a clinical guideline for cost-effective evaluation of pediatric patients first
      seen by a cardiologist for chest pain using a unique methodology termed the
      Standardized Clinical Assessment and Management Plans (SCAMPs). METHODS: A total
      of 1016 ambulatory patients, ages 7 to 21 years initially seen for chest pain at
      Boston Children's Hospital (BCH) or the New England Congenital Cardiology
      Association (NECCA) practices, were evaluated by using a SCAMPs chest pain
      guideline. Findings were analyzed for diagnostic elements, patterns of care, and
      compliance with the guideline. Results from the NECCA practices were compared
      with those of Boston Children's Hospital, a regional core academic center.
      RESULTS: Two patients had chest pain due to a cardiac etiology, 1 with
      pericarditis and 1 with an anomalous coronary artery origin. Testing performed
      outside of guideline recommendations demonstrated only incidental findings.
      Patients returning for persistent symptoms did not have cardiac disease. The
      pattern of care for the NECCA practices and BCH differed minimally. CONCLUSIONS:
      By using SCAMPs methodology, we have demonstrated that chest pain in children is
      rarely caused by heart disease and can be evaluated in the ambulatory setting
      efficiently and effectively using minimal resources. The methodology can be
      implemented regionally across a wide range of clinical practice settings and its
      approach can overcome a number of barriers that often limit clinical practice
      guideline implementation.

PMID- 24019420
TI  - Vitamin D3supplementation and childhood diarrhea: a randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of vitamin D3 supplementation on the
      incidence and risk for first and recurrent diarrheal illnesses among children in
      Kabul, Afghanistan. METHODS: This double-blind placebo-controlled trial
      randomized 3046 high-risk 1- to 11-month-old infants to receive 6 quarterly doses
      of oral vitamin D3 (cholecalciferol 100000 IU) or placebo in inner city Kabul.
      Data on diarrheal episodes (>= 3 loose/liquid stools in 24 hours) was gathered
      through active and passive surveillance over 18 months of follow-up. Time to
      first diarrheal illness was analyzed by using Kaplan-Meier plots. Incidence rates
      and hazard ratios (HRs) were calculated by using recurrent event Poisson
      regression models. RESULTS: No significant difference existed in survival time to
      first diarrheal illness (log rank P = .55). The incidences of diarrheal episodes
      were 3.43 (95% confidence interval [CI], 3.28-3.59) and 3.59 per child-year (95%
      CI, 3.44-3.76) in the placebo and intervention arms, respectively. Vitamin D3
      supplementation was found to have no effect on the risk for recurrent diarrheal
      disease in either intention-to-treat (HR, 1.05; 95% CI, 0.98-1.17; P = .15) or
      per protocol (HR, 1.05; 95% CI, 0.98-1.12; P = .14) analyses. The lack of
      preventive benefit remained when the randomized population was stratified by age
      groups, nutritional status, and seasons. CONCLUSIONS: Quarterly supplementation
      with vitamin D3 conferred no reduction on time to first illness or on the risk
      for recurrent diarrheal disease in this study. Similar supplementation to
      comparable populations is not recommended. Additional research in alternative
      settings may be helpful in elucidating the role of vitamin D3 supplementation for
      prevention of diarrheal diseases.

PMID- 24019422
TI  - Rejoinder: Need for a data-driven discussion on the socioeconomic patterning of
      cardiovascular health in India.

PMID- 24019421
TI  - Cohort profile: Andhra Pradesh Children and Parents Study (APCAPS).
AB  - The Andhra Pradesh Children and Parents Study (APCAPS) was originally established
      to study the long-term effects of early-life undernutrition on risk of
      cardiovascular disease. Its aims were subsequently expanded to include trans
      generational influences of other environmental and genetic factors on chronic
      diseases in rural India. It builds on the Hyderabad Nutrition Trial (HNT)
      conducted in 1987-90 to compare the effects on birthweight of a protein-calorie
      supplement for pregnant women and children. The index children of HNT and their
      mothers were retraced and examined in 2003-05, and the children re-examined as
      young adults aged 18-21 years in 2009-10. The cohort was expanded to include both
      parents and siblings of the index children in a recently completed follow-up
      conducted in 2010-12 (N=~6225 out of 10,213 participants). Recruitment of the
      remaining residents of these 29 villages (N=~55,000) in Ranga Reddy district of
      Andhra Pradesh is now under way. Extensive data on socio-demographic, lifestyle,
      medical, anthropometric, physiological, vascular and body composition measures,
      DNA, stored plasma, and assays of lipids and inflammatory markers on APCAPS
      participants are available. Details of how to access these data are available
      from the corresponding author.

PMID- 24019423
TI  - Adverse childhood experiences and child-to-adult height trajectories in the 1958
      British birth cohort.
AB  - BACKGROUND: Adverse childhood experiences (maltreatment and household
      dysfunction) are associated with adult cardiovascular disease (CVD). One possible
      pathway is through physical development, which has been linked to CVD risk. Our
      aim was to examine whether adverse childhood experiences are associated with
      child-to-adult height trajectories. METHOD: The 1958 British birth cohort
      (n=17,638) includes all born in one week in March 1958, followed up to mid
      adulthood. Height was measured at 7, 11 and 16 years (y) and adulthood (converted
      to standard deviation scores (SDS); >=1 height measurement n=16,444, adult leg
      length n=9180). Multivariate response models were used to examine the
      associations between childhood experiences (ascertained at 7 y and self-reported
      at 45 y) and child-to-adult height. RESULTS: Childhood neglect, prospectively
      assessed at 7 y, was associated with shorter stature throughout childhood: for
      each increment across a score ranging 0-7, average height reduced by 0.06 SDS
      (males) and 0.05 SDS (females) at 7 y (~0.3 cm), with smaller deficits (0.03 SDS,
      ~0.2 cm) in adulthood, after adjustment for parental height, birthweight and
      socio-economic factors. In males, the adult deficit was mainly due to shorter leg
      length. Household dysfunction was associated with shorter stature at 7-11 y, with
      adjusted deficits from 0.04 to 0.07 SDS per increment across a score ranging 0-7,
      but not at later ages. Adjusted models showed no associations for retrospectively
      reported abuse or neglect to 16 y. CONCLUSIONS: Those with a higher neglect score
      by 7 y grew more slowly, with deficits through to adulthood. No associations were
      found for abuse over the longer period to 16 y. Deficits associated with early
      life neglect and household dysfunction might have implications for adult CVD
      risks.

PMID- 24019424
TI  - Mediation analysis in epidemiology: methods, interpretation and bias.
AB  - In epidemiological studies it is often necessary to disentangle the pathways that
      link an exposure to an outcome. Typically the aim is to identify the total effect
      of the exposure on the outcome, the effect of the exposure that acts through a
      given set of mediators of interest (indirect effect) and the effect of the
      exposure unexplained by those same mediators (direct effect). The traditional
      approach to mediation analysis is based on adjusting for the mediator in standard
      regression models to estimate the direct effect. However, several methodological
      papers have shown that under a number of circumstances this traditional approach
      may produce flawed conclusions. Through a better understanding of the causal
      structure of the variables involved in the analysis, with a formal definition of
      direct and indirect effects in a counterfactual framework, alternative analytical
      methods have been introduced to improve the validity and interpretation of
      mediation analysis. In this paper, we review and discuss the impact of the three
      main sources of potential bias in the traditional approach to mediation analyses:
      (i) mediator-outcome confounding;(ii) exposure-mediator interaction and (iii)
      mediator-outcome confounding affected by the exposure. We provide examples and
      discuss the impact these sources have in terms of bias. 

PMID- 24019425
TI  - Suberin-associated fatty alcohols in Arabidopsis: distributions in roots and
      contributions to seed coat barrier properties.
AB  - Suberin is found in a variety of tissues, such as root endoderms and periderms,
      storage tuber periderms, tree cork layer, and seed coats. It acts as a
      hydrophobic barrier to control the movement of water, gases, and solutes as well
      as an antimicrobial barrier. Suberin consists of polymerized phenolics, glycerol,
      and a variety of fatty acid derivatives, including primary fatty alcohols. We
      have conducted an in-depth analysis of the distribution of the C18:0 to C22:0
      fatty alcohols in Arabidopsis (Arabidopsis thaliana) roots and found that only
      20% are part of the root suberin polymer, together representing about 5% of its
      aliphatic monomer composition, while the remaining 80% are found in the
      nonpolymeric (soluble) fraction. Down-regulation of Arabidopsis FATTY ACYL
      REDUCTASE1 (FAR1), FAR4, and FAR5, which collectively produce the fatty alcohols
      found in suberin, reduced their levels by 70% to 80% in (1) the polymeric and
      nonpolymeric fractions from roots of tissue culture-grown plants, (2) the suberin
      associated root waxes from 7-week-old soil-grown plants, and (3) the seed coat
      suberin polymer. By contrast, the other main monomers of suberin were not
      altered, indicating that reduced levels of fatty alcohols did not influence the
      suberin polymerization process. Nevertheless, the 75% reduction in total fatty
      alcohol and diol loads in the seed coat resulted in increased permeability to
      tetrazolium salts and a higher sensitivity to abscisic acid. These results
      suggest that fatty alcohols and diols play an important role in determining the
      functional properties of the seed coat suberin barrier. 

PMID- 24019426
TI  - Reduced Wall Acetylation proteins play vital and distinct roles in cell wall O
      acetylation in Arabidopsis.
AB  - The Reduced Wall Acetylation (RWA) proteins are involved in cell wall acetylation
      in plants. Previously, we described a single mutant, rwa2, which has about 20%
      lower level of O-acetylation in leaf cell walls and no obvious growth or
      developmental phenotype. In this study, we generated double, triple, and
      quadruple loss-of-function mutants of all four members of the RWA family in
      Arabidopsis (Arabidopsis thaliana). In contrast to rwa2, the triple and quadruple
      rwa mutants display severe growth phenotypes revealing the importance of wall
      acetylation for plant growth and development. The quadruple rwa mutant can be
      completely complemented with the RWA2 protein expressed under 35S promoter,
      indicating the functional redundancy of the RWA proteins. Nevertheless, the
      degree of acetylation of xylan, (gluco)mannan, and xyloglucan as well as overall
      cell wall acetylation is affected differently in different combinations of triple
      mutants, suggesting their diversity in substrate preference. The overall degree
      of wall acetylation in the rwa quadruple mutant was reduced by 63% compared with
      the wild type, and histochemical analysis of the rwa quadruple mutant stem
      indicates defects in cell differentiation of cell types with secondary cell
      walls. 

PMID- 24019427
TI  - Molecular steps in the immune signaling pathway evoked by plant elicitor
      peptides: Ca2+-dependent protein kinases, nitric oxide, and reactive oxygen
      species are downstream from the early Ca2+ signal.
AB  - Endogenous plant elicitor peptides (Peps) can act to facilitate immune signaling
      and pathogen defense responses. Binding of these peptides to the Arabidopsis
      (Arabidopsis thaliana) plasma membrane-localized Pep receptors (PEPRs) leads to
      cytosolic Ca(2+) elevation, an early event in a signaling cascade that activates
      immune responses. This immune response includes the amplification of signaling
      evoked by direct perception of pathogen-associated molecular patterns by plant
      cells under assault. Work included in this report further characterizes the Pep
      immune response and identifies new molecular steps in the signal transduction
      cascade. The PEPR coreceptor BRASSINOSTEROID-INSENSITIVE1 Associated Kinase1
      contributes to generation of the Pep-activated Ca(2+) signal and leads to
      increased defense gene expression and resistance to a virulent bacterial
      pathogen. Ca(2+)-dependent protein kinases (CPKs) decode the Ca(2+) signal, also
      facilitating defense gene expression and enhanced resistance to the pathogen.
      Nitric oxide and reduced nicotinamide adenine dinucleotide phosphate oxidase
      dependent reactive oxygen species generation (due to the function of Respiratory
      Burst Oxidase Homolog proteins D and F) are also involved downstream from the
      Ca(2+) signal in the Pep immune defense signal transduction cascade, as is the
      case with BRASSINOSTEROID-INSENSITIVE1 Associated Kinase1 and CPK5, CPK6, and
      CPK11. These steps of the pathogen defense response are required for maximal Pep
      immune activation that limits growth of a virulent bacterial pathogen in the
      plant. We find a synergism between function of the PEPR and Flagellin Sensing2
      receptors in terms of both nitric oxide and reactive oxygen species generation.
      Presented results are also consistent with the involvement of the secondary
      messenger cyclic GMP and a cyclic GMP-activated Ca(2+)-conducting channel in the
      Pep immune signaling pathway. 

PMID- 24019429
TI  - The impact of a school-based hygiene, water quality and sanitation intervention
      on soil-transmitted helminth reinfection: a cluster-randomized trial.
AB  - We conducted a cluster-randomized trial to assess the impact of a school-based
      water treatment, hygiene, and sanitation program on reducing infection with soil
      transmitted helminths (STHs) after school-based deworming. We assessed infection
      with STHs at baseline and then at two follow-up rounds 8 and 10 months after
      deworming. Forty government primary schools in Nyanza Province, Kenya were
      randomly selected and assigned to intervention or control arms. The intervention
      reduced reinfection prevalence (odds ratio [OR] 0.56, 95% confidence interval
      [CI] 0.31-1.00) and egg count (rate ratio [RR] 0.34, CI 0.15-0.75) of Ascaris
      lumbricoides. We found no evidence of significant intervention effects on the
      overall prevalence and intensity of Trichuris trichiura, hookworm, or Schistosoma
      mansoni reinfection. Provision of school-based sanitation, water quality, and
      hygiene improvements may reduce reinfection of STHs after school-based deworming,
      but the magnitude of the effects may be sex- and helminth species-specific.

PMID- 24019430
TI  - Weight gain and response to treatment for multidrug-resistant tuberculosis.
AB  - Alternatives to culture are needed in high burden countries to assess whether
      response to treatment of multidrug-resistant-tuberculosis (MDR-TB) is
      satisfactory. The objective was to assess the association of weight gain and
      treatment outcome. The methods included analysis of clinical, bacteriologic, and
      weight from 439 MDR-TB patients in the Philippines. Odds ratios (ORs) were
      calculated to determine whether 5% weight gain during the first 6 months of
      treatment was associated with outcome. Three hundred and ten (71%) patients were
      cured and 129 (29%) had poor outcomes (death, defaulted, or failed treatment).
      Fifty-three percent were underweight (body mass index [BMI] < 18.5 kg/m(2))
      before treatment. Five percent weight gain after completing 3 months of treatment
      was associated with good outcome among patients who were underweight before
      treatment (OR 2.1; 95% confidence interval [CI], 1.05 to 4.4). Baseline weight
      and degree of weight change during the first 6 months of treatment can help
      identify persons who are more likely to have poor outcomes and require other
      interventions.

PMID- 24019428
TI  - Identification of cyclic GMP-activated nonselective Ca2+-permeable cation
      channels and associated CNGC5 and CNGC6 genes in Arabidopsis guard cells.
AB  - Cytosolic Ca(2+) in guard cells plays an important role in stomatal movement
      responses to environmental stimuli. These cytosolic Ca(2+) increases result from
      Ca(2+) influx through Ca(2+)-permeable channels in the plasma membrane and Ca(2+)
      release from intracellular organelles in guard cells. However, the genes encoding
      defined plasma membrane Ca(2+)-permeable channel activity remain unknown in guard
      cells and, with some exceptions, largely unknown in higher plant cells. Here, we
      report the identification of two Arabidopsis (Arabidopsis thaliana) cation
      channel genes, CNGC5 and CNGC6, that are highly expressed in guard cells.
      Cytosolic application of cyclic GMP (cGMP) and extracellularly applied membrane
      permeable 8-Bromoguanosine 3',5'-cyclic monophosphate-cGMP both activated
      hyperpolarization-induced inward-conducting currents in wild-type guard cells
      using Mg(2+) as the main charge carrier. The cGMP-activated currents were
      strongly blocked by lanthanum and gadolinium and also conducted Ba(2+), Ca(2+),
      and Na(+) ions. cngc5 cngc6 double mutant guard cells exhibited dramatically
      impaired cGMP-activated currents. In contrast, mutations in CNGC1, CNGC2, and
      CNGC20 did not disrupt these cGMP-activated currents. The yellow fluorescent
      protein-CNGC5 and yellow fluorescent protein-CNGC6 proteins localize in the cell
      periphery. Cyclic AMP activated modest inward currents in both wild-type and
      cngc5cngc6 mutant guard cells. Moreover, cngc5 cngc6 double mutant guard cells
      exhibited functional abscisic acid (ABA)-activated hyperpolarization-dependent
      Ca(2+)-permeable cation channel currents, intact ABA-induced stomatal closing
      responses, and whole-plant stomatal conductance responses to darkness and changes
      in CO2 concentration. Furthermore, cGMP-activated currents remained intact in the
      growth controlled by abscisic acid2 and abscisic acid insensitive1 mutants. This
      research demonstrates that the CNGC5 and CNGC6 genes encode unique cGMP-activated
      nonselective Ca(2+)-permeable cation channels in the plasma membrane of
      Arabidopsis guard cells. 

PMID- 24019431
TI  - Fecal indicator bacteria contamination of fomites and household demand for
      surface disinfection products: a case study from Peru.
AB  - Surface-mediated disease transmission is understudied in developing countries,
      particularly in light of the evidence that surface concentrations of fecal
      bacteria typically exceed concentrations in developed countries by 10- to 100
      fold. In this study, we examined fecal indicator bacterial contamination of
      dinner plates at 21 households in four peri-urban communities in the Peruvian
      Amazon. We also used surveys to estimate household use of and demand for surface
      disinfectants at 280 households. Despite detecting total coliform, enterococci,
      and Escherichia coli on 86%, 43%, and 24% of plates sampled, respectively, less
      than one-third of households were regularly using bleach to disinfect surfaces.
      Among non-users of bleach, only 3.2% of respondents reported a new demand for
      bleach, defined as a high likelihood of using bleach within the next year. This
      study highlights the potential for marketing approaches to increase use of and
      demand for surface disinfectants to improve domestic hygiene.

PMID- 24019432
TI  - Comparison of the mosquito inoculation technique and quantitative real time
      polymerase chain reaction to measure dengue virus concentration.
AB  - An accurate measure of infectious dengue virus in human and mosquito tissues is
      critical to fully understand virus-host relationships, disease severity, viral
      fitness, and pathogenesis. In recent years, RNA copy number measured by
      quantitative real time-polymerase chain reaction has been used to measure dengue
      virus concentration in vitro and in vivo. In this study, we detail important
      differences in the measurement of viral growth kinetics in Vero and C6/36 tissue
      cultures, in Aedes aegypti mosquitoes, and in viremic human sera using RNA
      genomic equivalents and mosquito infectious dose 50 (MID50). Although there was
      reasonably good correlation between the two methods, RNA copy number was 2 to 5
      logs greater than infectious virus titers. These differences varied significantly
      depending on virus strain, viral platform, infectious virus assay, and viral
      growth phase. The results have important implications for the correct
      interpretation of biological and epidemiological data from experimental and
      clinical studies, and show that genomic equivalents should be interpreted with
      caution when used as a proxy for infectious virus in such studies.

PMID- 24019433
TI  - Prevalence and implications of cerebrospinal fluid leukocytosis in Papua New
      Guinean children hospitalized with severe malaria.
AB  - Cerebrospinal fluid (CSF) leukocytosis in severe malaria was assessed in 87
      children in Papua New Guinea participating in a detailed longitudinal
      observational study who had undergone lumbar puncture for further investigation
      of altered consciousness and/or convulsions. After rigorous exclusion of non
      malarial infection, 16 (20.5%) of 78 children with Plasmodium falciparum
      monoinfection but 0 of 9 with P. vivax/mixed-species malaria had a detectable CSF
      leukocytosis, which was unrelated to prior, including complex, seizures. There
      were eight children with a CSF leukocyte density > 10 cells/MUL (9.2% of the
      total sample), half of whom had cerebral malaria (4 of 22, 18.1%). Cerebrospinal
      fluid leukocytosis is infrequent in severe pediatric malaria, especially in
      children with P. vivax infections, and it is generally mild. Its presence in a
      blood slide-positive child should prompt consideration of alternative diagnoses
      and empiric antibiotic therapy.

PMID- 24019434
TI  - Rapid detection of Burkholderia pseudomallei in blood cultures using a monoclonal
      antibody-based immunofluorescent assay.
AB  - Melioidosis is a severe bacterial infection caused by Burkholderia pseudomallei.
      Rapid antimicrobial therapy is necessary to improve patient outcome, which is
      aided by direct detection of B. pseudomallei in clinical samples. A drawback for
      all antigen assays is that the number of B. pseudomallei in blood usually falls
      below the achievable level of detection. We performed a prospective cohort study
      of 461 patients with 541 blood cultures to evaluate the utility of a pre
      incubation step prior to detection of B. pseudomallei using a monoclonal antibody
      based immunofluorescent assay (Mab-IFA). The Mab-IFA was positive in 74 of 76
      patients with melioidosis (sensitivity = 97.4%), and negative in 385 patients who
      did not have blood cultures containing B. pseudomallei (specificity = 100%). The
      Mab-IFA could be a valuable supplementary tool for rapid detection. We recommend
      the use of the Mab-IFA to test blood cultures that flag positive in regions where
      melioidosis is endemic.

PMID- 24019435
TI  - Semi-quantitative scoring of an immunochromatographic test for circulating
      filarial antigen.
AB  - Abstract. The value of a semi-quantitative scoring of the filarial antigen test
      (Binax Now Filariasis card test, ICT) results was evaluated during a field survey
      in the Republic of Congo. One hundred and thirty-four (134) of 774 tests (17.3%)
      were clearly positive and were scored 1, 2, or 3; and 11 (1.4%) had questionable
      results. Wuchereria bancrofti microfilariae (mf) were detected in 41 of those 133
      individuals with an ICT test score >= 1 who also had a night blood smear; none of
      the 11 individuals with questionable ICT results harbored night mf. Cuzick's test
      showed a significant trend for higher microfilarial densities in groups with
      higher ICT scores (P < 0.001). The ICT scores were also significantly correlated
      with blood mf counts. Because filarial antigen levels provide an indication of
      adult worm infection intensity, our results suggest that semi-quantitative
      reading of the ICT may be useful for grading the intensity of filarial infections
      in individuals and populations. 

PMID- 24019436
TI  - Trends in antimalarial drug use in Africa.
AB  - Resistance to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) led the World
      Health Organization (WHO) to recommend changes in national drug policies. The
      time between policy changes and their implementation profoundly affects program
      impact. We developed a model based on data on antimalarial treatments, extracted
      from household surveys and national antimalarial policy information from the
      literature. Drug use in each country during the time period 1999-2011 and the
      trend in reduction of CQ use after policy change were estimated. The SP use
      estimates were correlated with the prevalence of a molecular marker associated
      with SP resistance. There was no spatial pattern in the country-level rate of
      reduction of CQ use, after policy change. In East Africa SP drug use was strongly
      correlated to resistance. If artemisinin resistance spreads to, or emerges in,
      Africa this methodology will be a valuable tool to estimate actual drug use and
      its impact on changes in drug efficacy.

PMID- 24019437
TI  - Application of a qPCR assay with melting curve analysis for detection and
      differentiation of protozoan oocysts in human fecal samples from Dominican
      Republic.
AB  - A quantitative polymerase chain reaction assay with melt curve analysis (qPCR
      MCA) was applied for the detection of protozoan oocysts in 501 human fecal
      samples collected in Dominican Republic. Samples were subjected to qPCR using
      universal coccidia primers targeting 18S rDNA to detect oocysts followed by MCA
      to identify oocyst species based on amplicon melting temperature. Putative
      positive samples were also tested by conventional PCR and microscopy.
      Cystoisospora belli (*3), Cryptosporidium parvum (*3), Cryptosporidium hominis
      (*5), Cryptosporidium meleagridis (*1), Cryptosporidium canis (*1), and
      Cyclospora cayetanensis (*9) were detected by qPCR-MCA and confirmed by
      sequencing. This assay consistently detected 10 copies of the cloned target
      fragment and can be considered more efficient and sensitive than microscopy
      flotation methods for detecting multiple species of oocysts in human feces. The
      qPCR-MCA is a reliable protozoan oocyst screening assay for use on clinical and
      environmental samples in public health, food safety and veterinary programs.

PMID- 24019438
TI  - Evaluation of chemical preparation on insect wing shape for geometric
      morphometrics.
AB  - Geometric morphometrics is an approach that has been increasingly applied in
      studies with insects. A limiting factor of this technique is that some mosquitoes
      have wings with dark spots or many scales, which jeopardizes the visualization of
      landmarks for morphometric analysis. Recently, in some studies, chemically
      treatment (staining) of the wings was used to improve the viewing of landmarks.
      In this study, we evaluated whether this method causes deformation of the wing
      veins and tested whether it facilitates the visualization of the most problematic
      landmarks. In addition, we tested whether mechanical removal of the scales was
      sufficient for this purpose. The results showed that the physical and chemical
      treatments are equally effective in improving visualization of the landmarks. The
      chemical method did not cause deformation of the wing. Thus, some of these
      treatments should be performed before beginning geometric morphometric analysis
      to avoid erroneous landmark digitizing.

PMID- 24019439
TI  - Density-dependent blood stage Plasmodium falciparum suppresses malaria super
      infection in a malaria holoendemic population.
AB  - Recent studies of Plasmodium berghei malaria in mice show that high blood-stage
      parasitemia levels inhibit the development of subsequent liver-stage infections.
      Whether a similar inhibitory effect on liver-stage Plasmodium falciparum by blood
      stage infection occurs in humans is unknown. We have analyzed data from a
      treatment-time-to-infection cohort of children < 10 years of age residing in a
      malaria holoendemic area of Kenya where people experience a new blood-stage
      infection approximately every 2 weeks. We hypothesized that if high parasitemia
      blocked the liver stage, then high levels of parasitemia should be followed by a
      "skipped" peak of parasitemia. Statistical analysis of "natural infection" field
      data and stochastic simulation of infection dynamics show that the data are
      consistent with high P. falciparum parasitemia inhibiting liver-stage parasite
      development in humans.

PMID- 24019440
TI  - Bartonella quintana in Cimex hemipterus, Rwanda.

PMID- 24019441
TI  - Population vulnerability to biannual cholera outbreaks and associated macro-scale
      drivers in the Bengal Delta.
AB  - The highly populated floodplains of the Bengal Delta have a long history of
      endemic and epidemic cholera outbreaks, both coastal and inland. Previous studies
      have not addressed the spatio-temporal dynamics of population vulnerability
      related to the influence of underlying large-scale processes. We analyzed spatial
      and temporal variability of cholera incidence across six surveillance sites in
      the Bengal Delta and their association with regional hydroclimatic and
      environmental drivers. More specifically, we use salinity and flood inundation
      modeling across the vulnerable districts of Bangladesh to test earlier proposed
      hypotheses on the role of these environmental variables. Our results show strong
      influence of seasonal and interannual variability in estuarine salinity on spring
      outbreaks and inland flooding on fall outbreaks. A large segment of the
      population in the Bengal Delta floodplains remain vulnerable to these biannual
      cholera transmission mechanisms that provide ecologic and environmental
      conditions for outbreaks over large geographic regions.

PMID- 24019442
TI  - Modeling risk categories to predict the longitudinal prevalence of childhood
      diarrhea in Indonesia.
AB  - We present an innovative approach for analyzing diarrheal prevalence data that
      uses latent variables to model the relationships between multiple, interdependent
      environmental risk factors, and socioeconomic mediators. This strategy was
      applied to elucidate diarrheal longitudinal prevalence risk factors in children 1
      4 years of age in low-income areas of Jakarta, Indonesia. Through a prospective
      cohort study, we identified 257 children who had at least one episode of
      diarrhea. At the onset of the study, we collected responses to 44 indicators,
      covering a wide range of previously identified diarrhea risk factors, including
      demographic and socioeconomic factors. We used exploratory factor analysis to
      uncover four latent categories of risk factors and their respective indicators
      from the initial pool of 44 indicators. Thereafter, we used structural equation
      modeling to model the relationships between the four risk categories and
      diarrheal longitudinal prevalence, controlling for socioeconomic and demographic
      covariates. Our final model elucidated several pathways to longitudinal diarrheal
      prevalence. Most notably, poverty exerts its effect on increased diarrheal
      prevalence via dual pathways: poor household hygiene and food quality,
      controlling for covariates. Implications of this and other findings for disease
      control in Jakarta are discussed.

PMID- 24019443
TI  - Association between hemorrhagic fever with renal syndrome epidemic and climate
      factors in Heilongjiang Province, China.
AB  - The purpose of this study was to quantify the relationship between climate
      variation and transmission of hemorrhagic fever with renal syndrome (HFRS) in
      Heilongjiang Province, a highly endemic area for HFRS in China. Monthly notified
      HFRS cases and climatic data for 2001-2009 in Heilongjiang Province were
      collected. Using a seasonal autoregressive integrated moving average model, we
      found that relative humidity with a one-month lag (beta = -0.010, P = 0.003) and
      a three-month lag (beta = 0.008, P = 0.003), maximum temperature with a two-month
      lag (beta = 0.082, P = 0.028), and southern oscillation index with a two-month
      lag (beta = -0.048, P = 0.019) were significantly associated with HFRS
      transmission. Our study also showed that predicted values expected under the
      seasonal autoregressive integrated moving average model were highly consistent
      with observed values (Adjusted R(2) = 83%, root mean squared error = 108). Thus,
      findings may help add to the knowledge gap of the role of climate factors in HFRS
      transmission in China and also assist national local health authorities in the
      development/refinement of a better strategy to prevent HFRS transmission.

PMID- 24019444
TI  - Author response: longitudinal changes in retinal nerve fiber layer thickness
      after vitrectomy for rhegmatogenous retinal detachment.

PMID- 24019445
TI  - Characterization of coronary atherosclerosis by magnetic resonance imaging.

PMID- 24019447
TI  - ECG challenge: September 10, 2013.

PMID- 24019446
TI  - Translation of high-density lipoprotein function into clinical practice: current
      prospects and future challenges.

PMID- 24019448
TI  - Severe mitral stenosis secondary to Hunter's syndrome.

PMID- 24019449
TI  - Mycetoma involving the heart.

PMID- 24019451
TI  - Letter by Apostolakis et al regarding article, "renal dysfunction as a predictor
      of stroke and systemic embolism in patients with nonvalvular atrial fibrillation:
      validation of the R2CHADS2 index in the ROCKET AF (Rivaroxaban Once-Daily, Oral,
      Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of
      Stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (Anticoagulation and
      Risk Factors in Atrial Fibrillation) study cohorts".

PMID- 24019452
TI  - Response to letter regarding article, "renal dysfunction as a predictor of stroke
      and systemic embolism in patients with nonvalvular atrial fibrillation:
      validation of the R2CHADS2 index in the ROCKET AF (Rivaroxaban Once-Daily, Oral,
      Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of
      Stroke and Embolism Trial in Atrial Fibrillation) and ATRIA (Anticoagulation and
      Risk Factors in Atrial Fibrillation) study cohorts".

PMID- 24019458
TI  - Inhibition of androgen receptor and beta-catenin activity in prostate cancer.
AB  - Androgen receptor (AR) is the major therapeutic target in aggressive prostate
      cancer. However, targeting AR alone can result in drug resistance and disease
      recurrence. Therefore, simultaneous targeting of multiple pathways could in
      principle be an effective approach to treating prostate cancer. Here we provide
      proof-of-concept that a small-molecule inhibitor of nuclear beta-catenin activity
      (called C3) can inhibit both the AR and beta-catenin-signaling pathways that are
      often misregulated in prostate cancer. Treatment with C3 ablated prostate cancer
      cell growth by disruption of both beta-catenin/T-cell factor and beta-catenin/AR
      protein interaction, reflecting the fact that T-cell factor and AR have
      overlapping binding sites on beta-catenin. Given that AR interacts with, and is
      transcriptionally regulated by beta-catenin, C3 treatment also resulted in
      decreased occupancy of beta-catenin on the AR promoter and diminished AR and
      AR/beta-catenin target gene expression. Interestingly, C3 treatment resulted in
      decreased AR binding to target genes accompanied by decreased recruitment of an
      AR and beta-catenin cofactor, coactivator-associated arginine methyltransferase 1
      (CARM1), providing insight into the unrecognized function of beta-catenin in
      prostate cancer. Importantly, C3 inhibited tumor growth in an in vivo xenograft
      model and blocked renewal of bicalutamide-resistant sphere-forming cells,
      indicating the therapeutic potential of this approach. 

PMID- 24019459
TI  - Regional and seasonal response of a West Nile virus vector to climate change.
AB  - Climate change will affect the abundance and seasonality of West Nile virus (WNV)
      vectors, altering the risk of virus transmission to humans. Using downscaled
      general circulation model output, we calculate a WNV vector's response to climate
      change across the southern United States using process-based modeling. In the
      eastern United States, Culex quinquefasciatus response to projected climate
      change displays a latitudinal and elevational gradient. Projected summer
      population depressions as a result of increased immature mortality and habitat
      drying are most severe in the south and almost absent further north; extended
      spring and fall survival is ubiquitous. Much of California also exhibits a
      bimodal pattern. Projected onset of mosquito season is delayed in the
      southwestern United States because of extremely dry and hot spring and summers;
      however, increased temperature and late summer and fall rains extend the mosquito
      season. These results are unique in being a broad-scale calculation of the
      projected impacts of climate change on a WNV vector. The results show that,
      despite projected widespread future warming, the future seasonal response of C.
      quinquefasciatus populations across the southern United States will not be
      homogeneous, and will depend on specific combinations of local and regional
      conditions. 

PMID- 24019460
TI  - Early developmental emergence of human amygdala-prefrontal connectivity after
      maternal deprivation.
AB  - Under typical conditions, medial prefrontal cortex (mPFC) connections with the
      amygdala are immature during childhood and become adult-like during adolescence.
      Rodent models show that maternal deprivation accelerates this development,
      prompting examination of human amygdala-mPFC phenotypes following maternal
      deprivation. Previously institutionalized youths, who experienced early maternal
      deprivation, exhibited atypical amygdala-mPFC connectivity. Specifically, unlike
      the immature connectivity (positive amygdala-mPFC coupling) of comparison
      children, children with a history of early adversity evidenced mature
      connectivity (negative amygdala-mPFC coupling) and thus, resembled the adolescent
      phenotype. This connectivity pattern was mediated by the hormone cortisol,
      suggesting that stress-induced modifications of the hypothalamic-pituitary
      adrenal axis shape amygdala-mPFC circuitry. Despite being age-atypical, negative
      amygdala-mPFC coupling conferred some degree of reduced anxiety, although anxiety
      was still significantly higher in the previously institutionalized group. These
      findings suggest that accelerated amygdala-mPFC development is an ontogenetic
      adaptation in response to early adversity. 

PMID- 24019461
TI  - Thirst-dependent risk preferences in monkeys identify a primitive form of wealth.
AB  - Experimental economic techniques have been widely used to evaluate human risk
      attitudes, but how these measured attitudes relate to overall individual wealth
      levels is unclear. Previous noneconomic work has addressed this uncertainty in
      animals by asking the following: (i) Do our close evolutionary relatives share
      both our risk attitudes and our degree of economic rationality? And (ii) how does
      the amount of food or water one holds (a nonpecuniary form of "wealth") alter
      risk attitudes in these choosers? Unfortunately, existing noneconomic studies
      have provided conflicting insights from an economic point of view. We therefore
      used standard techniques from human experimental economics to measure monkey risk
      attitudes for water rewards as a function of blood osmolality (an objective
      measure of how much water the subjects possess). Early in training, monkeys
      behaved randomly, consistently violating first-order stochastic dominance and
      monotonicity. After training, they behaved like human choosers--technically
      consistent in their choices and weakly risk averse (i.e., risk averse or risk
      neutral on average)--suggesting that well-trained monkeys can serve as a model
      for human choice behavior. As with attitudes about money in humans, these risk
      attitudes were strongly wealth dependent; as the animals became "poorer," risk
      aversion increased, a finding incompatible with some models of wealth and risk in
      human decision making.

PMID- 24019462
TI  - Watching energy transfer in metalloporphyrin heterodimers using stimulated X-ray
      Raman spectroscopy.
AB  - Understanding the excitation energy transfer mechanism in multiporphyrin arrays
      is key for designing artificial light-harvesting devices and other molecular
      electronics applications. Simulations of the stimulated X-ray Raman spectroscopy
      signals of a Zn/Ni porphyrin heterodimer induced by attosecond X-ray pulses show
      that these signals can directly reveal electron-hole pair motions. These dynamics
      are visualized by a natural orbital decomposition of the valence electron
      wavepackets. 

PMID- 24019463
TI  - Lysine 63-linked polyubiquitination is required for EGF receptor degradation.
AB  - Ubiquitination mediates endocytosis and endosomal sorting of various signaling
      receptors, transporters, and channels. However, the relative importance of mono-
      versus polyubiquitination and the role of specific types of polyubiquitin
      linkages in endocytic trafficking remain controversial. We used mass spectrometry
      based targeted proteomics to show that activated epidermal growth factor receptor
      (EGFR) is ubiquitinated by one to two short (two to three ubiquitins)
      polyubiquitin chains mainly linked via lysine 63 (K63) or conjugated with a
      single monoubiquitin. Multimonoubiquitinated EGFR species were not found. To
      directly test whether K63 polyubiquitination is necessary for endocytosis and
      post-endocytic sorting of EGFR, a chimeric protein, in which the K63 linkage
      specific deubiquitination enzyme AMSH [associated molecule with the Src homology
      3 domain of signal transducing adaptor molecule (STAM)] was fused to the carboxyl
      terminus of EGFR, was generated. MS analysis of EGFR-AMSH ubiquitination
      demonstrated that the fraction of K63 linkages was substantially reduced, whereas
      relative amounts of monoubiquitin and K48 linkages increased, compared with that
      of wild-type EGFR. EGFR-AMSH was efficiently internalized into early endosomes,
      but, importantly, the rates of ligand-induced sorting to late endosomes and
      degradation of EGFR-AMSH were dramatically decreased. The slow degradation of
      EGFR-AMSH resulted in the sustained signaling activity of this chimeric receptor.
      Ubiquitination patterns, rate of endosomal sorting, and signaling kinetics of
      EGFR fused with the catalytically inactive mutant of AMSH were reversed to
      normal. Altogether, the data are consistent with the model whereby short K63
      linked polyubiquitin chains but not multimonoubiquitin provide an increased
      avidity for EGFR interactions with ubiquitin adaptors, thus allowing rapid
      sorting of activated EGFR to the lysosomal degradation pathway. 

PMID- 24019464
TI  - Decisions on the fly in cellular sensory systems.
AB  - Cells send and receive signals through pathways that have been defined in great
      detail biochemically, and it is often presumed that the signals convey only level
      information. Cell signaling in the presence of noise is extensively studied but
      only rarely is the speed required to make a decision considered. However, in the
      immune system, rapidly developing embryos, and cellular response to stress, fast
      and accurate actions are required. Statistical theory under the rubric of
      "exploit-explore" quantifies trade-offs between decision speed and accuracy and
      supplies rigorous performance bounds and algorithms that realize them. We show
      that common protein phosphorylation networks can implement optimal decision
      theory algorithms and speculate that the ubiquitous chemical modifications to
      receptors during signaling actually perform analog computations. We quantify
      performance trade-offs when the cellular system has incomplete knowledge of the
      data model. For the problem of sensing the time when the composition of a ligand
      mixture changes, we find a nonanalytic dependence on relative concentrations and
      specify the number of parameters needed for near-optimal performance and how to
      adjust them. The algorithms specify the minimal computation that has to take
      place on a single receptor before the information is pooled across the cell. 

PMID- 24019465
TI  - ATP-binding cassette transporter controls leaf surface secretion of anticancer
      drug components in Catharanthus roseus.
AB  - The Madagascar periwinkle (Catharanthus roseus) is highly specialized for the
      biosynthesis of many different monoterpenoid indole alkaloids (MIAs), many of
      which have powerful biological activities. Such MIAs include the commercially
      important chemotherapy drugs vinblastine, vincristine, and other synthetic
      derivatives that are derived from the coupling of catharanthine and vindoline.
      However, previous studies have shown that biosynthesis of these MIAs involves
      extensive movement of metabolites between specialized internal leaf cells and the
      leaf epidermis that require the involvement of unknown secretory processes for
      mobilizing catharanthine to the leaf surface and vindoline to internal leaf
      cells. Spatial separation of vindoline and catharanthine provides a clear
      explanation for the low levels of dimers that accumulate in intact plants. The
      present work describes the molecular cloning and functional identification of a
      unique catharanthine transporter (CrTPT2) that is expressed predominantly in the
      epidermis of young leaves. CrTPT2 gene expression is activated by treatment with
      catharanthine, and its in planta silencing redistributes catharanthine to
      increase the levels of catharanthine-vindoline drug dimers in the leaves.
      Phylogenetic analysis shows that CrTPT2 is closely related to a key transporter
      involved in cuticle assembly in plants and that may be unique to MIA-producing
      plant species, where it mediates secretion of alkaloids to the plant surface. 

PMID- 24019466
TI  - Human development of the ability to learn from bad news.
AB  - Humans show a natural tendency to discount bad news while incorporating good news
      into beliefs (the "good news-bad news effect"), an effect that may help explain
      seemingly irrational risk taking. Understanding how this bias develops with age
      is important because adolescents are prone to engage in risky behavior; thus,
      educating them about danger is crucial. We reveal a striking valence-dependent
      asymmetry in how belief updating develops with age. In the ages tested (9-26 y),
      younger age was associated with inaccurate updating of beliefs in response to
      undesirable information regarding vulnerability. In contrast, the ability to
      update beliefs accurately in response to desirable information remained
      relatively stable with age. This asymmetry was mediated by adequate computational
      use of positive but not negative estimation errors to alter beliefs. The results
      are important for understanding how belief formation develops and might help
      explain why adolescents do not respond adequately to warnings. 

PMID- 24019467
TI  - Regulation of GDF-11 and myostatin activity by GASP-1 and GASP-2.
AB  - Myostatin (MSTN) and growth and differentiation factor-11 (GDF-11) are highly
      related TGF-beta family members that have distinct biological functions. MSTN is
      expressed primarily in skeletal muscle and acts to limit muscle growth. GDF-11 is
      expressed more widely and plays multiple roles, including regulating axial
      skeletal patterning during development. Several MSTN and GDF-11 binding proteins
      have been identified, including GDF-associated serum protein-1 (GASP-1) and GASP
      2, which are capable of inhibiting the activities of these ligands. Here, we show
      that GASP-1 and GASP-2 act by blocking the initial signaling event (namely, the
      binding of the ligand to the type II receptor). Moreover, we show that mice
      lacking Gasp1 and Gasp2 have phenotypes consistent with overactivity of MSTN and
      GDF-11. Specifically, we show that Gasp2(-/-) mice have posteriorly directed
      transformations of the axial skeleton, which contrast with the anteriorly
      directed transformations seen in Gdf11(-/-) mice. We also show that both Gasp1(-/
      ) and Gasp2(-/-) mice have reductions in muscle weights, a shift in fiber type
      from fast glycolytic type IIb fibers to fast oxidative type IIa fibers, and
      impaired muscle regeneration ability, which are the reverse of what are seen in
      Mstn(-/-) mice. All of these findings suggest that both GASP-1 and GASP-2 are
      important modulators of GDF-11 and MSTN activity in vivo. 

PMID- 24019468
TI  - In-fiber production of polymeric particles for biosensing and encapsulation.
AB  - Polymeric micro- and nanoparticles are becoming a mainstay in biomedicine,
      medical diagnostics, and therapeutics, where they are used in implementing
      sensing mechanisms, as imaging contrast agents, and in drug delivery. Current
      approaches to the fabrication of such particles are typically finely tuned to
      specific monomer or polymer species, size ranges, and structures. We present a
      general scalable methodology for fabricating uniformly sized spherical polymeric
      particles from a wide range of polymers produced with complex internal
      architectures and continuously tunable diameters extending from the millimeter
      scale down to 50 nm. Controllable access to such a wide range of sizes enables
      broad applications in cancer treatment, immunology, and vaccines. Our approach
      harnesses thermally induced, predictable fluid instabilities in composite
      core/cladding polymer fibers drawn from a macroscopic scaled-up model called a
      "preform." Through a stack-and-draw process, we produce fibers containing a
      multiplicity of identical cylindrical cores made of the polymers of choice
      embedded in a polymer cladding. The instability leads to the breakup of the
      initially intact cores, independent of the polymer chemistry, into necklaces of
      spherical particles held in isolation within the cladding matrix along the entire
      fiber length. We demonstrate here surface functionalization of the extracted
      particles for biodetection through specific protein-protein interactions,
      volumetric encapsulation of a biomaterial in spherical polymeric shells, and the
      combination of both surface and volumetric functionalities in the same particle.
      These particles used in distinct modalities may be produced from the desired
      biocompatible polymer by changing only the geometry of the macroscopic preform
      from which the fiber is drawn. 

PMID- 24019469
TI  - Herbivore exploits orally secreted bacteria to suppress plant defenses.
AB  - Induced plant defenses in response to herbivore attack are modulated by cross
      talk between jasmonic acid (JA)- and salicylic acid (SA)-signaling pathways. Oral
      secretions from some insect herbivores contain effectors that overcome these
      antiherbivore defenses. Herbivores possess diverse microbes in their digestive
      systems and these microbial symbionts can modify plant-insect interactions;
      however, the specific role of herbivore-associated microbes in manipulating plant
      defenses remains unclear. Here, we demonstrate that Colorado potato beetle
      (Leptinotarsa decemlineata) larvae exploit bacteria in their oral secretions to
      suppress antiherbivore defenses in tomato (Solanum lycopersicum). We found that
      antibiotic-untreated larvae decreased production of JA and JA-responsive
      antiherbivore defenses, but increased SA accumulation and SA-responsive gene
      expression. Beetles benefit from down-regulating plant defenses by exhibiting
      enhanced larval growth. In SA-deficient plants, suppression was not observed,
      indicating that suppression of JA-regulated defenses depends on the SA-signaling
      pathway. Applying bacteria isolated from larval oral secretions to wounded plants
      confirmed that three microbial symbionts belonging to the genera
      Stenotrophomonas, Pseudomonas, and Enterobacter are responsible for defense
      suppression. Additionally, reinoculation of these bacteria to antibiotic-treated
      larvae restored their ability to suppress defenses. Flagellin isolated from
      Pseudomonas sp. was associated with defense suppression. Our findings show that
      the herbivore exploits symbiotic bacteria as a decoy to deceive plants into
      incorrectly perceiving the threat as microbial. By interfering with the normal
      perception of herbivory, beetles can evade antiherbivore defenses of its host. 

PMID- 24019470
TI  - Phase behavior and critical activated dynamics of limited-valence DNA nanostars.
AB  - Colloidal particles with directional interactions are key in the realization of
      new colloidal materials with possibly unconventional phase behaviors. Here we
      exploit DNA self-assembly to produce bulk quantities of "DNA stars" with three or
      four sticky terminals, mimicking molecules with controlled limited valence.
      Solutions of such molecules exhibit a consolution curve with an upper critical
      point, whose temperature and concentration decrease with the valence. Upon
      approaching the critical point from high temperature, the intensity of the
      scattered light diverges with a power law, whereas the intensity time
      autocorrelation functions show a surprising two-step relaxation, somehow
      reminiscent of glassy materials. The slow relaxation time exhibits an Arrhenius
      behavior with no signs of criticality, demonstrating a unique scenario where the
      critical slowing down of the concentration fluctuations is subordinate to the
      large lifetime of the DNA bonds, with relevant analogies to critical dynamics in
      polymer solutions. The combination of equilibrium and dynamic behavior of DNA
      nanostars demonstrates the potential of DNA molecules in diversifying the
      pathways toward collective properties and self-assembled materials, beyond the
      range of phenomena accessible with ordinary molecular fluids. 

PMID- 24019471
TI  - Processing of meteoritic organic materials as a possible analog of early
      molecular evolution in planetary environments.
AB  - The composition of the Sutter's Mill meteorite insoluble organic material was
      studied both in toto by solid-state NMR spectroscopy of the powders and by gas
      chromatography-mass spectrometry analyses of compounds released upon their
      hydrothermal treatment. Results were compared with those obtained for other
      meteorites of diverse classifications (Murray, GRA 95229, Murchison, Orgueil, and
      Tagish Lake) and found to be so far unique in regard to the molecular species
      released. These include, in addition to O-containing aromatic compounds, complex
      polyether- and ester-containing alkyl molecules of prebiotic appeal and never
      detected in meteorites before. The Sutter's Mill fragments we analyzed had likely
      been altered by heat, and the hydrothermal conditions of the experiments
      realistically mimic early Earth settings, such as near volcanic activity or
      impact craters. On this basis, the data suggest a far larger availability of
      meteoritic organic materials for planetary environments than previously assumed
      and that molecular evolution on the early Earth could have benefited from
      accretion of carbonaceous meteorites both directly with soluble compounds and,
      for a more protracted time, through alteration, processing, and release from
      their insoluble organic materials. 

PMID- 24019472
TI  - Bio-inspired synthesis yields a tricyclic indoline that selectively resensitizes
      methicillin-resistant Staphylococcus aureus (MRSA) to beta-lactam antibiotics.
AB  - The continuous emergence of resistant bacteria has become a major worldwide
      health threat. The current development of new antibacterials has lagged far
      behind. To discover reagents to fight against resistant bacteria, we initiated a
      chemical approach by synthesizing and screening a small molecule library,
      reminiscent of the polycyclic indole alkaloids. Indole alkaloids are a class of
      structurally diverse natural products, many of which were isolated from plants
      that have been used as traditional medicine for millennia. Specifically, we
      adapted an evolutionarily conserved biosynthetic strategy and developed a concise
      and unified diversity synthesis pathway. Using this pathway, we synthesized 120
      polycyclic indolines that contain 26 distinct skeletons and a wide variety of
      functional groups. A tricyclic indoline, Of1, was discovered to selectively
      potentiate the activity of beta-lactam antibiotics in multidrug-resistant
      methicillin-resistant Staphylococcus aureus (MRSA), but not in methicillin
      sensitive S. aureus. In addition, we found that Of1 itself does not have
      antiproliferative activity but can resensitize several MRSA strains to the beta
      lactam antibiotics that are widely used in the clinic, such as an extended
      spectrum beta-lactam antibiotic amoxicillin/clavulanic acid and a first
      generation cephalosporin cefazolin. These data suggest that Of1 is a unique
      selective resistance-modifying agent for beta-lactam antibiotics, and it may be
      further developed to fight against resistant bacteria in the clinic. 

PMID- 24019473
TI  - Efficient water oxidation catalyzed by homogeneous cationic cobalt porphyrins
      with critical roles for the buffer base.
AB  - A series of cationic cobalt porphyrins was found to catalyze electrochemical
      water oxidation to O2 efficiently at room temperature in neutral aqueous
      solution. Co-5,10,15,20-tetrakis-(1,3-dimethylimidazolium-2-yl)porphyrin, with a
      highly electron-deficient meso-dimethylimidazolium porphyrin, was the most
      effective catalyst. The O2 formation rate was 170 nmol . cm(-2) . min(-1) (k(obs)
      = 1.4 * 10(3) s(-1)) with a Faradaic efficiency near 90%. Mechanistic
      investigations indicate the generation of a Co(IV)-O porphyrin cation radical as
      the reactive oxidant, which has accumulated two oxidizing equivalents above the
      Co(III) resting state of the catalyst. The buffer base in solution was shown to
      play several critical roles during the catalysis by facilitating both redox
      coupled proton transfer processes leading to the reactive oxidant and subsequent
      O-O bond formation. More basic buffer anions led to lower catalytic onset
      potentials, extending below 1 V. This homogeneous cobalt-porphyrin system was
      shown to be robust under active catalytic conditions, showing negligible
      decomposition over hours of operation. Added EDTA or ion exchange resin caused no
      catalyst poisoning, indicating that cobalt ions were not released from the
      porphyrin macrocycle during catalysis. Likewise, surface analysis by energy
      dispersive X-ray spectroscopy of the working electrodes showed no deposition of
      heterogeneous cobalt films. Taken together, the results indicate that Co
      5,10,15,20-tetrakis-(1,3-dimethylimidazolium-2-yl)porphyrin is an efficient,
      homogeneous, single-site water oxidation catalyst.

PMID- 24019474
TI  - Sensitive periods for the functional specialization of the neural system for
      human face processing.
AB  - The aim of the study was to identify possible sensitive phases in the development
      of the processing system for human faces. We tested the neural processing of
      faces in 11 humans who had been blind from birth and had undergone cataract
      surgery between 2 mo and 14 y of age. Pictures of faces and houses, scrambled
      versions of these pictures, and pictures of butterflies were presented while
      event-related potentials were recorded. Participants had to respond to the
      pictures of butterflies (targets) only. All participants, even those who had been
      blind from birth for several years, were able to categorize the pictures and to
      detect the targets. In healthy controls and in a group of visually impaired
      individuals with a history of developmental or incomplete congenital cataracts,
      the well-known enhancement of the N170 (negative peak around 170 ms) event
      related potential to faces emerged, but a face-sensitive response was not
      observed in humans with a history of congenital dense cataracts. By contrast,
      this group showed a similar N170 response to all visual stimuli, which was
      indistinguishable from the N170 response to faces in the controls. The face
      sensitive N170 response has been associated with the structural encoding of
      faces. Therefore, these data provide evidence for the hypothesis that the
      functional differentiation of category-specific neural representations in humans,
      presumably involving the elaboration of inhibitory circuits, is dependent on
      experience and linked to a sensitive period. Such functional specialization of
      neural systems seems necessary to archive high processing proficiency. 

PMID- 24019475
TI  - Supramolecular polymers with tunable topologies via hierarchical coordination
      driven self-assembly and hydrogen bonding interfaces.
AB  - A powerful strategy to obtain complex supramolecular materials is the bottom-up
      construction of noncovalently bound materials by hierarchical self-assembly. This
      assembly process involves stepwise, uniform increases to the architectural
      complexity of a substrate, starting from discrete precursors and growing in
      dimensionality through controlled reactivity to a final product. Herein, two
      orthogonal processes are exploited: coordination-driven self-assembly and
      hydrogen bonding. The former relies on the predictable formation of metal-ligand
      bonds wherein the directionalities of the rigid precursors used determines the
      structural outcome. The latter uses 2-ureido-4-pyrimidinone interfaces that are
      structurally robust by virtue of the quadruple hydrogen bonding that can occur
      between subunits. By combining these two processes into a single system, it is
      possible to generate hierarchical materials that preserve the attractive
      tunability associated with discrete supramolecular coordination complexes. For
      instance, the synthesis of a one-dimensional chain comprising linked metalla
      rhomboids is readily adapted to a 2D cross-linked hexagonal network by simply
      selecting a different metal acceptor precursor as an assembly component. The
      specific interactions between subunits, in this case platinum(II)-pyridyl bonds
      and the quadruple H-bonding of ureidopyrimidinone, are unchanged, establishing a
      unique strategy to obtain supramolecular polymers with marked topological
      differences with minimal synthetic redesign. In addition, the structural rigidity
      imposed by the inclusion of the platinum metallacycles serves to minimize the
      formation of cyclic oligomers, increasing the efficacy of formation and improving
      the properties of the resultant materials. Furthermore, this study taps the
      potential of organoplatinum(II) metallacycles in materials science. 

PMID- 24019476
TI  - Acrylamide concentration determines the direction and magnitude of helical
      membrane protein gel shifts.
AB  - SDS/PAGE is universally used in biochemistry, cell biology, and immunology to
      resolve minute protein amounts readily from tissue and cell extracts. Although
      molecular weights of water-soluble proteins are reliably determined from their
      SDS/PAGE mobility, most helical membrane proteins, which comprise 20-30% of the
      human genome and the majority of drug targets, migrate to positions that have for
      decades been unpredictably slower or faster than their actual formula weight,
      often confounding their identification. Using de novo designed transmembrane
      mimetic polypeptides that match the composition of helical membrane-spanning
      sequences, we quantitate anomalous SDS/PAGE fractionation of helical membrane
      proteins by comparing the relative mobilities of these polypeptides with typical
      water-soluble reference proteins on Laemmli gels. We find that both the net
      charge and effective molecular size of the migrating particles of transmembrane
      mimetic species exceed those of the corresponding reference proteins and that gel
      acrylamide concentration dictates the impact of these two factors on the
      direction and magnitude of anomalous migration. Algorithms we derived from these
      data compensate for this differential effect of acrylamide concentration on the
      SDS/PAGE mobility of a variety of natural membrane proteins. Our results provide
      a unique means to predict anomalous migration of membrane proteins, thereby
      facilitating straightforward determination of their molecular weights via
      SDS/PAGE. 

PMID- 24019477
TI  - CYP2R1 is a major, but not exclusive, contributor to 25-hydroxyvitamin D
      production in vivo.
AB  - Bioactivation of vitamin D consists of two sequential hydroxylation steps to
      produce 1alpha,25-dihydroxyvitamin D3. It is clear that the second or 1alpha
      hydroxylation step is carried out by a single enzyme, 25-hydroxyvitamin D 1alpha
      hydroxylase CYP27B1. However, it is not certain what enzyme or enzymes are
      responsible for the initial 25-hydroxylation. An excellent case has been made for
      vitamin D 25-hydroxylase CYP2R1, but this hypothesis has not yet been tested. We
      have now produced Cyp2r1 (-/-) mice. These mice had greater than 50% reduction in
      serum 25-hydroxyvitamin D3. Curiously, the 1alpha,25-dihydroxyvitamin D3 level in
      the serum remained unchanged. These mice presented no health issues. A double
      knockout of Cyp2r1 and Cyp27a1 maintained a similar circulating level of 25
      hydroxyvitamin D3 and 1alpha,25-dihydroxyvitamin D3. Our results support the idea
      that the CYP2R1 is the major enzyme responsible for 25-hydroxylation of vitamin
      D, but clearly a second, as-yet unknown, enzyme is another contributor to this
      important step in vitamin D activation. 

PMID- 24019478
TI  - Protein hydrogen exchange at residue resolution by proteolytic fragmentation mass
      spectrometry analysis.
AB  - Hydrogen exchange technology provides a uniquely powerful instrument for
      measuring protein structural and biophysical properties, quantitatively and in a
      nonperturbing way, and determining how these properties are implemented to
      produce protein function. A developing hydrogen exchange-mass spectrometry method
      (HX MS) is able to analyze large biologically important protein systems while
      requiring only minuscule amounts of experimental material. The major remaining
      deficiency of the HX MS method is the inability to deconvolve HX results to
      individual amino acid residue resolution. To pursue this goal we used an
      iterative optimization program (HDsite) that integrates recent progress in
      multiple peptide acquisition together with previously unexamined isotopic
      envelope-shape information and a site-resolved back-exchange correction. To test
      this approach, residue-resolved HX rates computed from HX MS data were compared
      with extensive HX NMR measurements, and analogous comparisons were made in
      simulation trials. These tests found excellent agreement and revealed the
      important computational determinants. 

PMID- 24019479
TI  - Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class
      switch recombination.
AB  - Preceding antibody constant regions are switch (S) regions varying in length and
      repeat density that are targets of activation-induced cytidine deaminase. We
      asked how participating S regions influence each other to orchestrate
      rearrangements at the IgH locus by engineering mice in which the weakest S
      region, Sepsilon, is replaced with prominent recombination hotspot SMU. These
      mice produce copious polyclonal IgE upon challenge, providing a platform to study
      IgE biology and therapeutic interventions. The insertion enhances epsilon germ
      line transcript levels, shows a preference for direct vs. sequential switching,
      and reduces intraswitch recombination events at native SMU. These results suggest
      that the sufficiency of SMU to mediate IgH rearrangements may be influenced by
      context-dependent cues. 

PMID- 24019480
TI  - Coalescence and genetic diversity in sexual populations under selection.
AB  - In sexual populations, selection operates neither on the whole genome, which is
      repeatedly taken apart and reassembled by recombination, nor on individual
      alleles that are tightly linked to the chromosomal neighborhood. The resulting
      interference between linked alleles reduces the efficiency of selection and
      distorts patterns of genetic diversity. Inference of evolutionary history from
      diversity shaped by linked selection requires an understanding of these patterns.
      Here, we present a simple but powerful scaling analysis identifying the unit of
      selection as the genomic "linkage block" with a characteristic length, ,
      determined in a self-consistent manner by the condition that the rate of
      recombination within the block is comparable to the fitness differences between
      different alleles of the block. We find that an asexual model with the strength
      of selection tuned to that of the linkage block provides an excellent description
      of genetic diversity and the site frequency spectra compared with computer
      simulations. This linkage block approximation is accurate for the entire spectrum
      of strength of selection and is particularly powerful in scenarios with many
      weakly selected loci. The latter limit allows us to characterize coalescence,
      genetic diversity, and the speed of adaptation in the infinitesimal model of
      quantitative genetics. 

PMID- 24019481
TI  - A chemostat array enables the spatio-temporal analysis of the yeast proteome.
AB  - Observing cellular responses to perturbations is central to generating and
      testing hypotheses in biology. We developed a massively parallel microchemostat
      array capable of growing and observing 1,152 yeast-GFP strains on the single-cell
      level with 20 min time resolution. We measured protein abundance and localization
      changes in 4,085 GFP-tagged strains in response to methyl methanesulfonate and
      analyzed 576 GFP strains in five additional conditions for a total of more than
      10,000 unique experiments, providing a systematic view of the yeast proteome in
      flux. We observed that processing bodies formed rapidly and synchronously in
      response to UV irradiation, and in conjunction with 506 deletion-GFP strains,
      identified four gene disruptions leading to abnormal ribonucleotide-diphosphate
      reductase (Rnr4) localization. Our microchemostat platform enables the large
      scale interrogation of proteomes in flux and permits the concurrent observation
      of protein abundance, localization, cell size, and growth parameters on the
      single-cell level for thousands of microbial cultures in one experiment. 

PMID- 24019482
TI  - Chemically armed mercenary ants protect fungus-farming societies.
AB  - The ants are extraordinary in having evolved many lineages that exploit closely
      related ant societies as social parasites, but social parasitism by distantly
      related ants is rare. Here we document the interaction dynamics among a
      Sericomyrmex fungus-growing ant host, a permanently associated parasitic guest
      ant of the genus Megalomyrmex, and a raiding agro-predator of the genus
      Gnamptogenys. We show experimentally that the guest ants protect their host
      colonies against agro-predator raids using alkaloid venom that is much more
      potent than the biting defenses of the host ants. Relatively few guest ants are
      sufficient to kill raiders that invariably exterminate host nests without a
      cohabiting guest ant colony. We also show that the odor of guest ants discourages
      raider scouts from recruiting nestmates to host colonies. Our results imply that
      Sericomyrmex fungus-growers obtain a net benefit from their costly guest ants
      behaving as a functional soldier caste to meet lethal threats from agro-predator
      raiders. The fundamentally different life histories of the agro-predators and
      guest ants appear to facilitate their coexistence in a negative frequency
      dependent manner. Because a guest ant colony is committed for life to a single
      host colony, the guests would harm their own interests by not defending the host
      that they continue to exploit. This conditional mutualism is analogous to chronic
      sickle cell anemia enhancing the resistance to malaria and to episodes in human
      history when mercenary city defenders offered either net benefits or imposed net
      costs, depending on the level of threat from invading armies. 

PMID- 24019483
TI  - Semisynthetic K+ channels show that the constricted conformation of the
      selectivity filter is not the C-type inactivated state.
AB  - C-type inactivation of K(+) channels plays a key role in modulating cellular
      excitability. During C-type inactivation, the selectivity filter of a K(+)
      channel changes conformation from a conductive to a nonconductive state. Crystal
      structures of the KcsA channel determined at low K(+) or in the open state
      revealed a constricted conformation of the selectivity filter, which was proposed
      to represent the C-type inactivated state. However, structural studies on other
      K(+) channels do not support the constricted conformation as the C-type
      inactivated state. In this study, we address whether the constricted conformation
      of the selectivity filter is in fact the C-type inactivated state. The
      constricted conformation can be blocked by substituting the first conserved
      glycine in the selectivity filter with the unnatural amino acid d-Alanine.
      Protein semisynthesis was used to introduce d-Alanine into the selectivity
      filters of the KcsA channel and the voltage-gated K(+) channel KvAP. For
      semisynthesis of the KvAP channel, we developed a modular approach in which
      chemical synthesis is limited to the selectivity filter whereas the rest of the
      protein is obtained by recombinant means. Using the semisynthetic KcsA and KvAP
      channels, we show that blocking the constricted conformation of the selectivity
      filter does not prevent inactivation, which suggests that the constricted
      conformation is not the C-type inactivated state. 

PMID- 24019484
TI  - Hydrogen sulphide pathway contributes to the enhanced human platelet aggregation
      in hyperhomocysteinemia.
AB  - Homocysteine is metabolized to methionine by the action of 5,10
      methylenetetrahydrofolate reductase (MTHFR). Alternatively, by the
      transulfuration pathway, homocysteine is transformed to hydrogen sulphide (H2S),
      through multiple steps involving cystathionine beta-synthase and cystathionine
      gamma-lyase. Here we have evaluated the involvement of H2S in the thrombotic
      events associated with hyperhomocysteinemia. To this purpose we have used
      platelets harvested from healthy volunteers or patients newly diagnosed with
      hyperhomocysteinemia with a C677T polymorphism of the MTHFR gene (MTHFR++). NaHS
      (0.1-100 uM) or l-cysteine (0.1-100 uM) significantly increased platelet
      aggregation harvested from healthy volunteers induced by thrombin receptor
      activator peptide-6 amide (2 uM) in a concentration-dependent manner. This
      increase was significantly potentiated in platelets harvested from MTHFR++
      carriers, and it was reversed by the inhibition of either cystathionine beta
      synthase or cystathionine gamma-lyase. Similarly, in MTHFR++ carriers, the
      content of H2S was significantly higher in either platelets or plasma compared
      with healthy volunteers. Interestingly, thromboxane A2 production was markedly
      increased in response to both NaHS or l-cysteine in platelets of healthy
      volunteers. The inhibition of phospholipase A2, cyclooxygenase, or blockade of
      the thromboxane receptor markedly reduced the effects of H2S. Finally,
      phosphorylated-phospholipase A2 expression was significantly higher in MTHFR++
      carriers compared with healthy volunteers. In conclusion, the H2S pathway is
      involved in the prothrombotic events occurring in hyperhomocysteinemic patients. 

PMID- 24019485
TI  - Ca2+ channel nanodomains boost local Ca2+ amplitude.
AB  - Local Ca(2+) signals through voltage-gated Ca(2+) channels (CaVs) drive synaptic
      transmission, neural plasticity, and cardiac contraction. Despite the importance
      of these events, the fundamental relationship between flux through a single CaV
      channel and the Ca(2+) signaling concentration within nanometers of its pore has
      resisted empirical determination, owing to limitations in the spatial resolution
      and specificity of fluorescence-based Ca(2+) measurements. Here, we exploited
      Ca(2+)-dependent inactivation of CaV channels as a nanometer-range Ca(2+)
      indicator specific to active channels. We observed an unexpected and dramatic
      boost in nanodomain Ca(2+) amplitude, ten-fold higher than predicted on
      theoretical grounds. Our results uncover a striking feature of CaV nanodomains,
      as diffusion-restricted environments that amplify small Ca(2+) fluxes into
      enormous local Ca(2+) concentrations. This Ca(2+) tuning by the physical
      composition of the nanodomain may represent an energy-efficient means of local
      amplification that maximizes information signaling capacity, while minimizing
      global Ca(2+) load. 

PMID- 24019487
TI  - Broad-scale predictability of carbohydrates and exopolymers in Antarctic and
      Arctic sea ice.
AB  - Sea ice can contain high concentrations of dissolved organic carbon (DOC), much
      of which is carbohydrate-rich extracellular polymeric substances (EPS) produced
      by microalgae and bacteria inhabiting the ice. Here we report the concentrations
      of dissolved carbohydrates (dCHO) and dissolved EPS (dEPS) in relation to algal
      standing stock [estimated by chlorophyll (Chl) a concentrations] in sea ice from
      six locations in the Southern and Arctic Oceans. Concentrations varied
      substantially within and between sampling sites, reflecting local ice conditions
      and biological content. However, combining all data revealed robust statistical
      relationships between dCHO concentrations and the concentrations of different
      dEPS fractions, Chl a, and DOC. These relationships were true for whole ice
      cores, bottom ice (biomass rich) sections, and colder surface ice. The
      distribution of dEPS was strongly correlated to algal biomass, with the highest
      concentrations of both dEPS and non-EPS carbohydrates in the bottom horizons of
      the ice. Complex EPS was more prevalent in colder surface sea ice horizons.
      Predictive models (validated against independent data) were derived to enable the
      estimation of dCHO concentrations from data on ice thickness, salinity, and
      vertical position in core. When Chl a data were included a higher level of
      prediction was obtained. The consistent patterns reflected in these relationships
      provide a strong basis for including estimates of regional and seasonal
      carbohydrate and dEPS carbon budgets in coupled physical-biogeochemical models,
      across different types of sea ice from both polar regions. 

PMID- 24019486
TI  - Ets-1 facilitates nuclear entry of NFAT proteins and their recruitment to the IL
      2 promoter.
AB  - E26 transformation-specific sequence 1 (Ets-1), the prototype of the ETS family
      of transcription factors, is critical for the expression of IL-2 by murine Th
      cells; however, its mechanism of action is still unclear. Here we show that Ets-1
      is also essential for optimal production of IL-2 by primary human Th cells.
      Although Ets-1 negatively regulates the expression of Blimp1, a known suppressor
      of IL-2 expression, ablation of B lymphocyte-induced maturation protein 1
      (Blimp1) does not rescue the expression of IL-2 by Ets-1-deficient Th cells.
      Instead, Ets-1 physically and functionally interacts with the nuclear factor of
      activated T-cells (NFAT) and is required for the recruitment of NFAT to the IL-2
      promoter. In addition, Ets-1 is located in both the nucleus and cytoplasm of
      resting Th cells. Nuclear Ets-1 quickly exits the nucleus in response to calcium
      dependent signals and competes with NFAT proteins for binding to protein
      components of noncoding RNA repressor of NFAT complex (NRON), which serves as a
      cytoplasmic trap for phosphorylated NFAT proteins. This nuclear exit of Ets-1
      precedes rapid nuclear entry of NFAT and Ets-1 deficiency results in impaired
      nuclear entry, but not dephosphorylation, of NFAT proteins. Thus, Ets-1 promotes
      the expression of IL-2 by modulating the activity of NFAT. 

PMID- 24019488
TI  - Quantitative analysis of intra-Golgi transport shows intercisternal exchange for
      all cargo.
AB  - The mechanisms controlling the transport of proteins through the Golgi stack of
      mammalian and plant cells is the subject of intense debate, with two models,
      cisternal progression and intercisternal exchange, emerging as major contenders.
      A variety of transport experiments have claimed support for each of these models.
      We reevaluate these experiments using a single quantitative coarse-grained
      framework of intra-Golgi transport that accounts for both transport models and
      their many variants. Our analysis makes a definitive case for the existence of
      intercisternal exchange both for small membrane proteins and large protein
      complexes--this implies that membrane structures larger than the typical protein
      coated vesicles must be involved in transport. Notwithstanding, we find that
      current observations on protein transport cannot rule out cisternal progression
      as contributing significantly to the transport process. To discriminate between
      the different models of intra-Golgi transport, we suggest experiments and an
      analysis based on our extended theoretical framework that compare the dynamics of
      transiting and resident proteins. 

PMID- 24019490
TI  - Complete mitochondrial genome sequence of a Middle Pleistocene cave bear
      reconstructed from ultrashort DNA fragments.
AB  - Although an inverse relationship is expected in ancient DNA samples between the
      number of surviving DNA fragments and their length, ancient DNA sequencing
      libraries are strikingly deficient in molecules shorter than 40 bp. We find that
      a loss of short molecules can occur during DNA extraction and present an improved
      silica-based extraction protocol that enables their efficient retrieval. In
      combination with single-stranded DNA library preparation, this method enabled us
      to reconstruct the mitochondrial genome sequence from a Middle Pleistocene cave
      bear (Ursus deningeri) bone excavated at Sima de los Huesos in the Sierra de
      Atapuerca, Spain. Phylogenetic reconstructions indicate that the U. deningeri
      sequence forms an early diverging sister lineage to all Western European Late
      Pleistocene cave bears. Our results prove that authentic ancient DNA can be
      preserved for hundreds of thousand years outside of permafrost. Moreover, the
      techniques presented enable the retrieval of phylogenetically informative
      sequences from samples in which virtually all DNA is diminished to fragments
      shorter than 50 bp. 

PMID- 24019489
TI  - Functional and structural architecture of the human dorsal frontoparietal
      attention network.
AB  - The dorsal frontoparietal attention network has been subdivided into at least
      eight areas in humans. However, the circuitry linking these areas and the
      functions of different circuit paths remain unclear. Using a combination of
      neuroimaging techniques to map spatial representations in frontoparietal areas,
      their functional interactions, and structural connections, we demonstrate
      different pathways across human dorsal frontoparietal cortex for the control of
      spatial attention. Our results are consistent with these pathways computing
      object-centered and/or viewer-centered representations of attentional priorities
      depending on task requirements. Our findings provide an organizing principle for
      the frontoparietal attention network, where distinct pathways between frontal and
      parietal regions contribute to multiple spatial representations, enabling
      flexible selection of behaviorally relevant information. 

PMID- 24019491
TI  - Dissection of Cdk1-cyclin complexes in vivo.
AB  - Cyclin-dependent kinases (Cdks) are regulatory enzymes with temporal and spatial
      selectivity for their protein substrates that are governed by cell cycle
      regulated cyclin subunits. Specific cyclin-Cdk complexes bind to and
      phosphorylate target proteins, coupling their activity to cell cycle states. The
      identification of specific cyclin-Cdk substrates is challenging and so far, has
      largely been achieved through indirect correlation or use of in vitro techniques.
      Here, we use a protein-fragment complementation assay based on the optimized
      yeast cytosine deaminase to systematically identify candidate substrates of
      budding yeast Saccharomyces cerevisiae Cdk1 and show dependency on one or more
      regulatory cyclins. We identified known and candidate cyclin dependencies for
      many predicted protein kinase Cdk1 targets and showed elusory Clb3-Cdk1-specific
      phosphorylation of gamma-tubulin, thus establishing the timing of this event in
      controlling assembly of the mitotic spindle. Our strategy can be generally
      applied to identify substrates and accessory subunits of multisubunit protein
      complexes. 

PMID- 24019492
TI  - Mechanism for activation of mutated epidermal growth factor receptors in lung
      cancer.
AB  - The initiation of epidermal growth factor receptor (EGFR) kinase activity
      proceeds via an asymmetric dimerization mechanism in which a "donor" tyrosine
      kinase domain (TKD) contacts an "acceptor" TKD, leading to its activation. In the
      context of a ligand-induced dimer, identical wild-type EGFR TKDs are thought to
      assume the donor or acceptor roles in a random manner. Here, we present
      biochemical reconstitution data demonstrating that activated EGFR mutants found
      in lung cancer preferentially assume the acceptor role when coexpressed with WT
      EGFR. Mutated EGFRs show enhanced association with WT EGFR, leading to
      hyperphosphorylation of the WT counterpart. Mutated EGFRs also hyperphosphorylate
      the related erythroblastic leukemia viral oncogene (ErbB) family member, ErbB-2,
      in a similar manner. This directional "superacceptor activity" is particularly
      pronounced in the drug-resistant L834R/T766M mutant. A 4-A crystal structure of
      this mutant in the active conformation reveals an asymmetric dimer interface that
      is essentially the same as that in WT EGFR. Asymmetric dimer formation induces an
      allosteric conformational change in the acceptor subunit. Thus, superacceptor
      activity likely arises simply from a lower energetic cost associated with this
      conformational change in the mutant EGFR compared with WT, rather than from any
      structural alteration that impairs the donor role of the mutant. Collectively,
      these findings define a previously unrecognized mode of mutant-specific
      intermolecular regulation for ErbB receptors, knowledge of which could
      potentially be exploited for therapeutic benefit. 

PMID- 24019494
TI  - Presynaptic gating of excitation in the dorsal raphe nucleus by GABA.
AB  - The dorsal raphe nucleus (DR) controls forebrain serotonin neurotransmission to
      influence emotional states. GABA neurotransmission in the DR has been implicated
      in regulating sleep/wake states and influencing anxiety and aggression. To gain
      insight into how GABA regulates DR activity, we analyzed the organization of both
      GABA and glutamate axons in the rat DR using a high-resolution immunofluorescence
      technique, array tomography, as well as EM. This analysis revealed that a third
      or more of GABA-containing axons are organized in synaptic triads with a
      glutamatergic axon and a common postsynaptic target. Electrophysiological
      recordings showed that GABA has the capacity to presynaptically gate glutamate
      release in the DR through a combination of GABA-A and GABA-B receptor-mediated
      effects. Thus, GABA-glutamate synaptic triads are a common feature of the network
      architecture of the DR with the potential to regulate excitation of the nucleus. 

PMID- 24019495
TI  - QnAs with Ann M. Graybiel. Interview by Nicholette Zeliadt.

PMID- 24019496
TI  - Simultaneous modeling of visual saliency and value computation improves
      predictions of economic choice.
AB  - Many decisions we make require visually identifying and evaluating numerous
      alternatives quickly. These usually vary in reward, or value, and in low-level
      visual properties, such as saliency. Both saliency and value influence the final
      decision. In particular, saliency affects fixation locations and durations, which
      are predictive of choices. However, it is unknown how saliency propagates to the
      final decision. Moreover, the relative influence of saliency and value is
      unclear. Here we address these questions with an integrated model that combines a
      perceptual decision process about where and when to look with an economic
      decision process about what to choose. The perceptual decision process is modeled
      as a drift-diffusion model (DDM) process for each alternative. Using
      psychophysical data from a multiple-alternative, forced-choice task, in which
      subjects have to pick one food item from a crowded display via eye movements, we
      test four models where each DDM process is driven by (i) saliency or (ii) value
      alone or (iii) an additive or (iv) a multiplicative combination of both. We find
      that models including both saliency and value weighted in a one-third to two
      thirds ratio (saliency-to-value) significantly outperform models based on either
      quantity alone. These eye fixation patterns modulate an economic decision
      process, also described as a DDM process driven by value. Our combined model
      quantitatively explains fixation patterns and choices with similar or better
      accuracy than previous models, suggesting that visual saliency has a smaller, but
      significant, influence than value and that saliency affects choices indirectly
      through perceptual decisions that modulate economic decisions. 

PMID- 24019497
TI  - Discovery of the surface polarity gradient on iridescent Morpho butterfly scales
      reveals a mechanism of their selective vapor response.
AB  - For almost a century, the iridescence of tropical Morpho butterfly scales has
      been known to originate from 3D vertical ridge structures of stacked periodic
      layers of cuticle separated by air gaps. Here we describe a biological pattern of
      surface functionality that we have found in these photonic structures. This
      pattern is a gradient of surface polarity of the ridge structures that runs from
      their polar tops to their less-polar bottoms. This finding shows a biological
      pattern design that could stimulate numerous technological applications ranging
      from photonic security tags to self-cleaning surfaces, gas separators, protective
      clothing, sensors, and many others. As an important first step, this biomaterial
      property and our knowledge of its basis has allowed us to unveil a general
      mechanism of selective vapor response observed in the photonic Morpho
      nanostructures. This mechanism of selective vapor response brings a multivariable
      perspective for sensing, where selectivity is achieved within a single chemically
      graded nanostructured sensing unit, rather than from an array of separate
      sensors. 

PMID- 24019499
TI  - Testicular volume is inversely correlated with nurturing-related brain activity
      in human fathers.
AB  - Despite the well-documented benefits afforded the children of invested fathers in
      modern Western societies, some fathers choose not to invest in their children.
      Why do some men make this choice? Life History Theory offers an explanation for
      variation in parental investment by positing a trade-off between mating and
      parenting effort, which may explain some of the observed variance in human
      fathers' parenting behavior. We tested this hypothesis by measuring aspects of
      reproductive biology related to mating effort, as well as paternal nurturing
      behavior and the brain activity related to it. Both plasma testosterone levels
      and testes volume were independently inversely correlated with paternal
      caregiving. In response to viewing pictures of one's own child, activity in the
      ventral tegmental area--a key component of the mesolimbic dopamine reward and
      motivation system--predicted paternal caregiving and was negatively related to
      testes volume. Our results suggest that the biology of human males reflects a
      trade-off between mating effort and parenting effort, as indexed by testicular
      size and nurturing-related brain function, respectively.

PMID- 24019500
TI  - Protein domain mimetics as in vivo modulators of hypoxia-inducible factor
      signaling.
AB  - Selective blockade of gene expression by designed small molecules is a
      fundamental challenge at the interface of chemistry, biology, and medicine.
      Transcription factors have been among the most elusive targets in genetics and
      drug discovery, but the fields of chemical biology and genetics have evolved to a
      point where this task can be addressed. Herein we report the design, synthesis,
      and in vivo efficacy evaluation of a protein domain mimetic targeting the
      interaction of the p300/CBP coactivator with the transcription factor hypoxia
      inducible factor-1alpha. Our results indicate that disrupting this interaction
      results in a rapid down-regulation of hypoxia-inducible genes critical for cancer
      progression. The observed effects were compound-specific and dose-dependent. Gene
      expression profiling with oligonucleotide microarrays revealed effective
      inhibition of hypoxia-inducible genes with relatively minimal perturbation of
      nontargeted signaling pathways. We observed remarkable efficacy of the compound
      HBS 1 in suppressing tumor growth in the fully established murine xenograft
      models of renal cell carcinoma of the clear cell type. Our results suggest that
      rationally designed synthetic mimics of protein subdomains that target the
      transcription factor-coactivator interfaces represent a unique approach for in
      vivo modulation of oncogenic signaling and arresting tumor growth. 

PMID- 24019504
TI  - Micron-scale coherence in interphase chromatin dynamics.
AB  - Chromatin structure and dynamics control all aspects of DNA biology yet are
      poorly understood, especially at large length scales. We developed an approach,
      displacement correlation spectroscopy based on time-resolved image correlation
      analysis, to map chromatin dynamics simultaneously across the whole nucleus in
      cultured human cells. This method revealed that chromatin movement was coherent
      across large regions (4-5 um) for several seconds. Regions of coherent motion
      extended beyond the boundaries of single-chromosome territories, suggesting
      elastic coupling of motion over length scales much larger than those of genes.
      These large-scale, coupled motions were ATP dependent and unidirectional for
      several seconds, perhaps accounting for ATP-dependent directed movement of single
      genes. Perturbation of major nuclear ATPases such as DNA polymerase, RNA
      polymerase II, and topoisomerase II eliminated micron-scale coherence, while
      causing rapid, local movement to increase; i.e., local motions accelerated but
      became uncoupled from their neighbors. We observe similar trends in chromatin
      dynamics upon inducing a direct DNA damage; thus we hypothesize that this may be
      due to DNA damage responses that physically relax chromatin and block long
      distance communication of forces. 

PMID- 24019506
TI  - Seed shattering in a wild sorghum is conferred by a locus unrelated to
      domestication.
AB  - Suppression of seed shattering was a key step during crop domestication that we
      have previously suggested to be convergent among independent cereal lineages.
      Positional, association, expression, and mutant complementation data all
      implicate a WRKY transcription factor, SpWRKY, in conferring shattering to a wild
      sorghum relative, Sorghum propinquum. We hypothesize that SpWRKY functions in a
      manner analogous to Medicago and Arabidopsis homologs that regulate cell wall
      biosynthesis genes, with low expression toward the end of floral development
      derepressing downstream cell wall biosynthesis genes to allow deposition of
      lignin that initiates the abscission zone in the seed-pedicel junction. The
      recent discovery of a YABBY locus that confers shattering within Sorghum bicolor
      and other cereals validated our prior hypothesis that some parallel domestication
      may have been convergent. Ironically, however, the shattering allele of SpWRKY
      appears to be recently evolved in S. propinquum and illustrates a case in which
      the genetic control of a trait in a wild relative fails to extrapolate even to
      closely related crops. Remarkably, the SpWRKY and YABBY loci lie only 300 kb
      apart and may have appeared to be a single genetic locus in some sorghum
      populations. 

PMID- 24019507
TI  - Culture and behaviour in the English National Health Service: overview of lessons
      from a large multimethod study.
AB  - BACKGROUND: Problems of quality and safety persist in health systems worldwide.
      We conducted a large research programme to examine culture and behaviour in the
      English National Health Service (NHS). METHODS: Mixed-methods study involving
      collection and triangulation of data from multiple sources, including interviews,
      surveys, ethnographic case studies, board minutes and publicly available
      datasets. We narratively synthesised data across the studies to produce a
      holistic picture and in this paper present a high-level summary. RESULTS: We
      found an almost universal desire to provide the best quality of care. We
      identified many 'bright spots' of excellent caring and practice and high-quality
      innovation across the NHS, but also considerable inconsistency. Consistent
      achievement of high-quality care was challenged by unclear goals, overlapping
      priorities that distracted attention, and compliance-oriented bureaucratised
      management. The institutional and regulatory environment was populated by
      multiple external bodies serving different but overlapping functions. Some
      organisations found it difficult to obtain valid insights into the quality of the
      care they provided. Poor organisational and information systems sometimes left
      staff struggling to deliver care effectively and disempowered them from
      initiating improvement. Good staff support and management were also highly
      variable, though they were fundamental to culture and were directly related to
      patient experience, safety and quality of care. CONCLUSIONS: Our results
      highlight the importance of clear, challenging goals for high-quality care.
      Organisations need to put the patient at the centre of all they do, get smart
      intelligence, focus on improving organisational systems, and nurture caring
      cultures by ensuring that staff feel valued, respected, engaged and supported.

PMID- 24019508
TI  - Status of the down-regulated canine testis using two different GNRH agonist
      implants in comparison with the juvenile testis.
AB  - Testicular function in the dog was down-regulated using two different GNRH
      agonist implants, with adult and juvenile testes serving as controls. Treatment
      resulted in an increased percentage of the interstitial area and decreased area
      of Leydig cell nuclei. Expression of StAR and the steroidogenic enzymes
      cytochrome P450 side-chain cleavage enzyme (P450scc, CYP11A1) and cytochrome P450
      17alpha-hydroxylase-17,20-lyase (P450c17, CYP17A1) in Leydig cells was blocked at
      the mRNA and protein level, showing no differences between the two agonists.
      Staining for androgen receptor (AR) by immunohistochemistry was positive in
      Sertoli, Leydig and peritubular cells and some spermatogonia, with in situ
      hybridization confirming expression in Sertoli cells. At the mRNA level,
      expression of AR was not affected; however, translation was blocked (reduced
      percentage of AR-positive Sertoli cells), with the number of nuclei in basal
      position being decreased. In the juvenile testes, mRNA expression of StAR,
      CYP11A1 and CYP17A1 was higher compared with the other groups but distinctly
      lower for the AR. At the protein level, the expression was at the limit of
      detection for StAR; AR-positive Sertoli cells were not detected. Our observations
      show that the down-regulated testis is different from the juvenile one rather
      resembling the testicular status in seasonal breeders out of season. 

PMID- 24019509
TI  - Expression and regulation of secreted phosphoprotein 1 in the bovine corpus
      luteum and effects on T lymphocyte chemotaxis.
AB  - Secreted phosphoprotein 1 (SPP1) in the bovine corpus luteum (CL) regulates cell
      function during the transitional periods of luteinization and luteal regression.
      The objectives were to i) characterize SPP1 expression in the CL throughout the
      estrous cycle, ii) determine factors that regulate SPP1 expression in luteal
      cells, and iii) examine the role of SPP1 in lymphocyte chemotaxis, proliferation,
      and function. SPP1 mRNA was greater in fully functional (d10) CL and late cycle
      (d18) CL compared with developing (d4) CL. Additionally, SPP1 mRNA increased
      within 1 h and remained elevated 4 and 8 h following induction of luteolysis with
      prostaglandin (PG)F2alpha. Expression of the SPP1 receptor, beta3 integrin, was
      not different throughout the estrous cycle but decreased following induction of
      luteolysis. Expression of CD44 increased during the estrous cycle but did not
      change during luteal regression. In cultured luteal cells, SPP1 mRNA was
      upregulated by PGF2alpha and/or tumor necrosis factor alpha. Western blots
      revealed the presence of both full-length SPP1 and multiple cleavage products in
      cultured luteal cells and luteal tissue. Depletion of endogenous SPP1 did not
      hinder luteal cell-induced lymphocyte proliferation or lymphocyte phenotype but
      did inhibit lymphocyte migration toward luteal cells. Based on these data, it is
      concluded that SPP1 is initially activated to establish and maintain cellular
      interactions between steroidogenic and nonsteroidogenic cells during the
      development of the CL. Upon induction of luteolysis, SPP1 serves as a signaling
      molecule to recruit or activate immune cells to facilitate luteal regression and
      tissue degradation. 

PMID- 24019510
TI  - Characterization of a nodavirus replicase revealed a de novo initiation mechanism
      of RNA synthesis and terminal nucleotidyltransferase activity.
AB  - Nodaviruses are a family of positive-stranded RNA viruses with a bipartite genome
      of RNAs. In nodaviruses, genomic RNA1 encodes protein A, which is recognized as
      an RNA-dependent RNA polymerase (RdRP) and functions as the sole viral replicase
      protein responsible for its RNA replication. Although nodaviral RNA replication
      has been studied in considerable detail, and nodaviruses are well recognized
      models for investigating viral RNA replication, the mechanism(s) governing the
      initiation of nodaviral RNA synthesis have not been determined. In this study, we
      characterized the RdRP activity of Wuhan nodavirus (WhNV) protein A in detail and
      determined that this nodaviral protein A initiates RNA synthesis via a de novo
      mechanism, and this RNA synthesis initiation could be independent of other viral
      or cellular factors. Moreover, we uncovered that WhNV protein A contains a
      terminal nucleotidyltransferase (TNTase) activity, which is the first time such
      an activity has been identified in nodaviruses. We subsequently found that the
      TNTase activity could function in vitro to repair the 3' initiation site, which
      may be digested by cellular exonucleases, to ensure the efficiency and accuracy
      of viral RNA synthesis initiation. Furthermore, we determined the cis-acting
      elements for RdRP or TNTase activity at the 3'-end of positive or negative strand
      RNA1. Taken together, our data establish the de novo synthesis initiation
      mechanism and the TNTase activity of WhNV protein A, and this work represents an
      important advance toward understanding the mechanism(s) of nodaviral RNA
      replication. 

PMID- 24019511
TI  - Mitochondrial localized Stat3 promotes breast cancer growth via phosphorylation
      of serine 727.
AB  - Signal transducer and activator of transcription 3 (Stat3) is a key mediator in
      the development of many cancers. For 20 years, it has been assumed that Stat3
      mediates its biological activities as a nuclear localized transcription factor
      activated by many cytokines. However, recent studies from this laboratory and
      others indicate that Stat3 has an independent function in the mitochondria
      (mitoStat3) where it controls the activity of the electron transport chain (ETC)
      and mediates Ras-induced transformation of mouse embryo fibroblasts. The actions
      of mitoStat3 in controlling respiration and Ras transformation are mediated by
      the phosphorylation state of serine 727. To address the role of mitoStat3 in the
      pathogenesis of cells that are transformed, we used 4T1 breast cancer cells,
      which form tumors that metastasize in immunocompetent mice. Substitution of Ser
      727 for an alanine or aspartate in Stat3 that has a mitochondrial localization
      sequence, MLS-Stat3, has profound effects on tumor growth, complex I activity of
      the ETC, and accumulation of reactive oxygen species (ROS). Cells expressing MLS
      Stat3(S727A) display slower tumor growth, decreased complex I activity of the
      ETC, and increased ROS accumulation under hypoxia compared with cells expressing
      MLS-Stat3. In contrast, cells expressing MLS-Stat3(S727D) show enhanced tumor
      growth and complex I activity and decreased production of ROS. These results
      highlight the importance of serine 727 of mitoStat3 in breast cancer and suggest
      a novel role for mitoStat3 in regulation of ROS concentrations through its action
      on the ETC. 

PMID- 24019512
TI  - Ptc1 protein phosphatase 2C contributes to glucose regulation of SNF1/AMP
      activated protein kinase (AMPK) in Saccharomyces cerevisiae.
AB  - The SNF1/AMP-activated protein kinases (AMPKs) function in energy regulation in
      eukaryotic cells. SNF1/AMPKs are alphabetagamma heterotrimers that are activated
      by phosphorylation of the activation loop Thr on the catalytic subunit. Protein
      kinases that activate SNF1/AMPK have been identified, but the protein
      phosphatases responsible for dephosphorylation of the activation loop are less
      well defined. For Saccharomyces cerevisiae SNF1/AMPK, Reg1-Glc7 protein
      phosphatase 1 and Sit4 type 2A-related phosphatase function together to
      dephosphorylate Thr-210 on the Snf1 catalytic subunit during growth on high
      concentrations of glucose; reg1Delta and sit4Delta single mutations do not impair
      dephosphorylation when inappropriate glycogen synthesis, also caused by these
      mutations, is blocked. We here present evidence that Ptc1 protein phosphatase 2C
      also has a role in dephosphorylation of Snf1 Thr-210 in vivo. The sit4Delta
      ptc1Delta mutant exhibited partial defects in regulation of the phosphorylation
      state of Snf1. The reg1Delta ptc1Delta mutant was viable only when expressing
      mutant Snf1 proteins with reduced kinase activity, and Thr-210 phosphorylation of
      the mutant SNF1 heterotrimers was substantially elevated during growth on high
      glucose. This evidence, together with findings on the reg1Delta sit4Delta mutant,
      indicates that although Reg1-Glc7 plays the major role, all three phosphatases
      contribute to maintenance of the Snf1 activation loop in the dephosphorylated
      state during growth on high glucose. Ptc1 has overlapping functions with Reg1
      Glc7 and Sit4 in glucose regulation of SNF1/AMPK and cell viability. 

PMID- 24019513
TI  - Lipid absorption defects in intestine-specific microsomal triglyceride transfer
      protein and ATP-binding cassette transporter A1-deficient mice.
AB  - We have previously described apolipoprotein B (apoB)-dependent and -independent
      cholesterol absorption pathways and the role of microsomal triglyceride transfer
      protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways.
      To assess the contribution of these pathways to cholesterol absorption and to
      determine whether there are other pathways, we generated mice that lack MTP and
      ABCA1, individually and in combination, in the intestine. Intestinal deletions of
      Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%,
      respectively, whereas their combined deletion reduced it by 59%. Acute
      cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was
      reduced by 92-95% when MTP was deleted in the intestine alone or together with
      ABCA1. MTP deficiency significantly reduced triglyceride absorption, although
      ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids,
      but Mttp deficiency significantly increased intestinal levels of triglycerides
      and free fatty acids. Accumulation of intestinal free fatty acids, but not
      triglycerides, in Mttp-deficient intestines was prevented when mice were also
      deficient in intestinal ABCA1. Combined deficiency of these genes increased
      intestinal fatty acid oxidation as a consequence of increased expression of
      peroxisome proliferator-activated receptor-gamma (PPARgamma) and carnitine
      palmitoyltransferase 1alpha (CPT1alpha). These studies show that intestinal MTP
      and ABCA1 are critical for lipid absorption and are the main determinants of
      plasma and intestinal lipid levels. Reducing their activities might lower plasma
      lipid concentrations. 

PMID- 24019514
TI  - Identification of a region within the placental alkaline phosphatase mRNA that
      mediates p180-dependent targeting to the endoplasmic reticulum.
AB  - In both eukaryotic and prokaryotic cells, it has been recently established that
      mRNAs encoding secreted and membrane proteins can be localized to the surface of
      membranes via both translation-dependent and RNA element-mediated mechanisms.
      Previously, we showed that the placental alkaline phosphatase (ALPP) mRNA can be
      localized to the ER membrane independently of translation, and this localization
      is mediated by p180, an mRNA receptor present in the ER. In this article, we
      aimed to identify the cis-acting RNA element in ALPP. Using chimera constructs
      containing fragments of the ALPP mRNA, we demonstrate that the ER-localizing RNA
      element is present within the 3' end of the open reading frame and codes for a
      transmembrane domain. In addition, we show that this region requires p180 for
      efficient ER anchoring. Taken together, we provide the first insight into the
      nature of cis-acting ER-localizing RNA elements responsible for localizing mRNAs
      on the ER in mammalian cells. 

PMID- 24019515
TI  - General control nonderepressible 2 (GCN2) kinase protects oligodendrocytes and
      white matter during branched-chain amino acid deficiency in mice.
AB  - Branched-chain amino acid (BCAA) catabolism is regulated by branched-chain alpha
      keto acid dehydrogenase, an enzyme complex that is inhibited when phosphorylated
      by its kinase (BDK). Loss of BDK function in mice and humans causes BCAA
      deficiency and epilepsy with autistic features. In response to amino acid
      deficiency, phosphorylation of eukaryotic initiation factor 2alpha (eIF2~P) by
      general control nonderepressible 2 (GCN2) activates the amino acid stress
      response. We hypothesized that GCN2 functions to protect the brain during chronic
      BCAA deficiency. To test this idea, we generated mice lacking both Gcn2 and Bdk
      (GBDK) and examined the development of progeny. GBDK mice appeared normal at
      birth, but they soon stopped growing, developed severe ataxia, tremor, and
      anorexia, and died by postnatal day 15. BCAA levels in brain were diminished in
      both Bdk(-/-) and GBDK pups. Brains from Bdk(-/-) pups exhibited robust eIF2~P
      and amino acid stress response induction, whereas these responses were absent in
      GBDK mouse brains. Instead, myelin deficiency and diminished expression of myelin
      basic protein were noted in GBDK brains. Genetic markers of oligodendrocytes and
      astrocytes were also reduced in GBDK brains in association with apoptotic cell
      death in white matter regions of the brain. GBDK brains further demonstrated
      reduced Sod2 and Cat mRNA and increased Tnfalpha mRNA expression. The data are
      consistent with the idea that loss of GCN2 during BCAA deficiency compromises
      glial cell defenses to oxidative and inflammatory stress. We conclude that GCN2
      protects the brain from developing a lethal leukodystrophy in response to amino
      acid deficiencies. 

PMID- 24019516
TI  - Protection of a ceramide synthase 2 null mouse from drug-induced liver injury:
      role of gap junction dysfunction and connexin 32 mislocalization.
AB  - Very long chain (C22-C24) ceramides are synthesized by ceramide synthase 2
      (CerS2). A CerS2 null mouse displays hepatopathy because of depletion of C22-C24
      ceramides, elevation of C16-ceramide, and/or elevation of sphinganine.
      Unexpectedly, CerS2 null mice were resistant to acetaminophen-induced
      hepatotoxicity. Although there were a number of biochemical changes in the liver,
      such as increased levels of glutathione and multiple drug-resistant protein 4,
      these effects are unlikely to account for the lack of acetaminophen toxicity. A
      number of other hepatotoxic agents, such as d-galactosamine, CCl4, and
      thioacetamide, were also ineffective in inducing liver damage. All of these drugs
      and chemicals require connexin (Cx) 32, a key gap junction protein, to induce
      hepatotoxicity. Cx32 was mislocalized to an intracellular location in hepatocytes
      from CerS2 null mice, which resulted in accelerated rates of its lysosomal
      degradation. This mislocalization resulted from the altered membrane properties
      of the CerS2 null mice, which was exemplified by the disruption of detergent
      resistant membranes. The lack of acetaminophen toxicity and Cx32 mislocalization
      were reversed upon infection with recombinant adeno-associated virus expressing
      CerS2. We establish that Gap junction function is compromised upon altering the
      sphingolipid acyl chain length composition, which is of relevance for
      understanding the regulation of drug-induced liver injury. 

PMID- 24019517
TI  - Identification of cysteine residues in human cationic amino acid transporter hCAT
      2A that are targets for inhibition by N-ethylmaleimide.
AB  - In most cells, cationic amino acids such as l-arginine, l-lysine, and l-ornithine
      are transported by cationic (CAT) and y(+)L (y(+)LAT) amino acid transporters. In
      human erythrocytes, the cysteine-modifying agent N-ethylmaleimide (NEM) has been
      shown to inhibit system y(+) (most likely CAT-1), but not system y(+)L (Deves,
      R., Angelo, S., and Chavez, P. (1993) J. Physiol. 468, 753-766). We thus wondered
      if sensitivity to NEM distinguishes generally all CAT and y(+)LAT isoforms.
      Transport assays in Xenopus laevis oocytes established that indeed all human CATs
      (including the low affinity hCAT-2A), but neither y(+)LAT isoform, are inhibited
      by NEM. hCAT-2A inhibition was not due to reduced transporter expression in the
      plasma membrane, indicating that NEM reduces the intrinsic transporter activity.
      Individual mutation of each of the seven cysteine residues conserved in all CAT
      isoforms did not lead to NEM insensitivity of hCAT-2A. However, a cysteine-less
      mutant was no longer inhibited by NEM, suggesting that inhibition occurs through
      modification of more than one cysteine in hCAT-2A. Indeed, also the double mutant
      C33A/C273A was insensitive to NEM inhibition, whereas reintroduction of a
      cysteine at either position 33 or 273 in the cysteine-less mutant led to NEM
      sensitivity. We thus identified Cys-33 and Cys-273 in hCAT-2A as the targets of
      NEM inhibition. In addition, all proteins with Cys-33 mutations showed a
      pronounced reduction in transport activity, suggesting that, surprisingly, this
      residue, located in the cytoplasmic N terminus, is important for transporter
      function. 

PMID- 24019518
TI  - Identification of novel cholesterol-binding regions in Kir2 channels.
AB  - Inwardly rectifying potassium (Kir) channels play an important role in setting
      the resting membrane potential and modulating membrane excitability. We have
      recently shown that cholesterol regulates representative members of the Kir
      family and that in the majority of the cases, cholesterol suppresses channel
      function. Furthermore, recent data indicate that cholesterol regulates Kir
      channels by specific sterol-protein interactions, yet the location of the
      cholesterol binding site in Kir channels is unknown. Using a combined
      computational-experimental approach, we show that cholesterol may bind to two
      nonanular hydrophobic regions in the transmembrane domain of Kir2.1 located
      between adjacent subunits of the channel. The location of the binding regions
      suggests that cholesterol modulates channel function by affecting the hinging
      motion at the center of the pore-lining transmembrane helix that underlies
      channel gating either directly or through the interface between the N and C
      termini of the channel. 

PMID- 24019519
TI  - Disarming bacterial virulence through chemical inhibition of the DNA binding
      domain of an AraC-like transcriptional activator protein.
AB  - The misuse of antibiotics during past decades has led to pervasive antibiotic
      resistance in bacteria. Hence, there is an urgent need for the development of new
      and alternative approaches to combat bacterial infections. In most bacterial
      pathogens the expression of virulence is tightly regulated at the transcriptional
      level. Therefore, targeting pathogens with drugs that interfere with virulence
      gene expression offers an effective alternative to conventional antimicrobial
      chemotherapy. Many Gram-negative intestinal pathogens produce AraC-like proteins
      that control the expression of genes required for infection. In this study we
      investigated the prototypical AraC-like virulence regulator, RegA, from the mouse
      attaching and effacing pathogen, Citrobacter rodentium, as a potential drug
      target. By screening a small molecule chemical library and chemical optimization,
      we identified two compounds that specifically inhibited the ability of RegA to
      activate its target promoters and thus reduced expression of a number of proteins
      required for virulence. Biophysical, biochemical, genetic, and computational
      analyses indicated that the more potent of these two compounds, which we named
      regacin, disrupts the DNA binding capacity of RegA by interacting with amino acid
      residues within a conserved region of the DNA binding domain. Oral administration
      of regacin to mice, commencing 15 min before or 12 h after oral inoculation with
      C. rodentium, caused highly significant attenuation of intestinal colonization by
      the mouse pathogen comparable to that of an isogenic regA-deletion mutant. These
      findings demonstrate that chemical inhibition of the DNA binding domains of
      transcriptional regulators is a viable strategy for the development of
      antimicrobial agents that target bacterial pathogens. 

PMID- 24019520
TI  - A non-classical assembly pathway of Escherichia coli pore-forming toxin cytolysin
      A.
AB  - Cytolysin A (ClyA) is an alpha-pore forming toxin from pathogenic Escherichia
      coli (E. coli) and Salmonella enterica. Here, we report that E. coli ClyA
      assembles into an oligomeric structure in solution in the absence of either
      bilayer membranes or detergents at physiological temperature. These oligomers can
      rearrange to create transmembrane pores when in contact with detergents or
      biological membranes. Intrinsic fluorescence measurements revealed that oligomers
      adopted an intermediate state found during the transition between monomer and
      transmembrane pore. These results indicate that the water-soluble oligomer
      represents a prepore intermediate state. Furthermore, we show that ClyA does not
      form transmembrane pores on E. coli lipid membranes. Because ClyA is delivered to
      the target host cell in an oligomeric conformation within outer membrane vesicles
      (OMVs), our findings suggest ClyA forms a prepore oligomeric structure
      independently of the lipid membrane within the OMV. The proposed model for ClyA
      represents a non-classical pathway to attack eukaryotic host cells. 

PMID- 24019521
TI  - RNF185 is a novel E3 ligase of endoplasmic reticulum-associated degradation
      (ERAD) that targets cystic fibrosis transmembrane conductance regulator (CFTR).
AB  - In the endoplasmic reticulum (ER), misfolded or improperly assembled proteins are
      exported to the cytoplasm and degraded by the ubiquitin-proteasome pathway
      through a process called ER-associated degradation (ERAD). ER-associated E3
      ligases, which coordinate substrate recognition, export, and proteasome
      targeting, are key components of ERAD. Cystic fibrosis transmembrane conductance
      regulator (CFTR) is one ERAD substrate targeted to co-translational degradation
      by the E3 ligase RNF5/RMA1. RNF185 is a RING domain-containing polypeptide
      homologous to RNF5. We show that RNF185 controls the stability of CFTR and of the
      CFTRDeltaF508 mutant in a RING- and proteasome-dependent manner but does not
      control that of other classical ERAD model substrates. Reciprocally, its
      silencing stabilizes CFTR proteins. Turnover analyses indicate that, as RNF5,
      RNF185 targets CFTR to co-translational degradation. Importantly, however,
      simultaneous depletion of RNF5 and RNF185 profoundly blocks CFTRDeltaF508
      degradation not only during translation but also after synthesis is complete. Our
      data thus identify RNF185 and RNF5 as a novel E3 ligase module that is central to
      the control of CFTR degradation. 

PMID- 24019522
TI  - Histone H2A ubiquitination inhibits the enzymatic activity of H3 lysine 36
      methyltransferases.
AB  - Histone H3 lysine 27 (H3K27) methylation and H2A monoubiquitination (ubH2A) are
      two closely related histone modifications that regulate Polycomb silencing.
      Previous studies reported that H3K27 trimethylation (H3K27me3) rarely coexists
      with H3K36 di- or tri-methylation (H3K36me2/3) on the same histone H3 tails,
      which is partially controlled by the direct inhibition of the enzymatic activity
      of H3K27-specific methyltransferase PRC2. By contrast, H3K27 methylation does not
      affect the catalytic activity of H3K36-specific methyltransferases, suggesting
      other Polycomb mechanism(s) may negatively regulate the H3K36-specific
      methyltransferase(s). In this study, we established a simple protocol to purify
      milligram quantities of ubH2A from mammalian cells, which were used to
      reconstitute nucleosome substrates with fully ubiquitinated H2A. A number of
      histone methyltransferases were then tested on these nucleosome substrates.
      Notably, all of the H3K36-specific methyltransferases, including ASH1L, HYPB,
      NSD1, and NSD2 were inhibited by ubH2A, whereas the other histone
      methyltransferases, including PRC2, G9a, and Pr-Set7 were not affected by ubH2A.
      Together with previous reports, these findings collectively explain the mutual
      repulsion of H3K36me2/3 and Polycomb modifications. 

PMID- 24019524
TI  - Complex structure of the DNA-binding domain of AdpA, the global transcription
      factor in Streptomyces griseus, and a target duplex DNA reveals the structural
      basis of its tolerant DNA sequence specificity.
AB  - AdpA serves as the global transcription factor in the A-factor regulatory
      cascade, controlling the secondary metabolism and morphological differentiation
      of the filamentous bacterium Streptomyces griseus. AdpA binds to over 500
      operator regions with the consensus sequence 5'-TGGCSNGWWY-3' (where S is G or C,
      W is A or T, Y is T or C, and N is any nucleotide). However, it is still obscure
      how AdpA can control hundreds of genes. To elucidate the structural basis of this
      tolerant DNA recognition by AdpA, we focused on the interaction between the DNA
      binding domain of AdpA (AdpA-DBD), which consists of two helix-turn-helix motifs,
      and a target duplex DNA containing the consensus sequence 5'-TGGCGGGTTC-3'. The
      crystal structure of the AdpA-DBD-DNA complex and the mutant analysis of AdpA-DBD
      revealed its unique manner of DNA recognition, whereby only two arginine residues
      directly recognize the consensus sequence, explaining the strict recognition of G
      and C at positions 2 and 4, respectively, and the tolerant recognition of other
      positions of the consensus sequence. AdpA-DBD confers tolerant DNA sequence
      specificity to AdpA, allowing it to control hundreds of genes as a global
      transcription factor. 

PMID- 24019523
TI  - The power of two: arginine 51 and arginine 239* from a neighboring subunit are
      essential for catalysis in alpha-amino-beta-carboxymuconate-epsilon-semialdehyde
      decarboxylase.
AB  - Although the crystal structure of alpha-amino-beta-carboxymuconate-epsilon
      semialdehyde decarboxylase from Pseudomonas fluorescens was solved as a dimer,
      this enzyme is a mixture of monomer, dimer, and higher order structures in
      solution. In this work, we found that the dimeric state, not the monomeric state,
      is the functionally active form. Two conserved arginine residues are present in
      the active site: Arg-51 and an intruding Arg-239* from the neighboring subunit.
      In this study, they were each mutated to alanine and lysine, and all four mutants
      were catalytically inactive. The mutants were also incapable of accommodating
      pyridine-2,6-dicarboxylic acid, a competitive inhibitor of the native enzyme,
      suggesting that the two Arg residues are involved in substrate binding. It was
      also observed that the decarboxylase activity was partially recovered in a
      heterodimer hybridization experiment when inactive R51(A/K) and R239(A/K) mutants
      were mixed together. Of the 20 crystal structures obtained from mixing inactive
      R51A and R239A homodimers that diffracted to a resolution lower than 3.00 A, two
      structures are clearly R51A/R239A heterodimers and belong to the C2 space group.
      They were refined to 1.80 and 2.00 A resolutions, respectively. Four of the
      remaining crystals are apparently single mutants and belong to the P42212 space
      group. In the heterodimer structures, one active site is shown to contain dual
      mutation of Ala-51 and Ala-239*, whereas the other contains the native Arg-51 and
      Arg-239* residues, identical to the wild-type structure. Thus, these observations
      provide the foundation for a molecular mechanism by which the oligomerization
      state of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
      could regulate the enzyme activity. 

PMID- 24019525
TI  - Sequential steps in the assembly of the multimeric outer membrane secretin PulD.
AB  - Investigations into protein folding are largely dominated by studies on monomeric
      proteins. However, the transmembrane domain of an important group of membrane
      proteins is only formed upon multimerization. Here, we use in vitro translation
      coupled folding and insertion into artificial liposomes to investigate kinetic
      steps in the assembly of one such protein, the outer membrane secretin PulD of
      the bacterial type II secretion system. Analysis of the folding kinetics,
      measured by the acquisition of distinct determinants of the native state,
      provides unprecedented evidence for a sequential multistep process initiated by
      membrane-driven oligomerization. The effects of varying the lipid composition of
      the liposomes indicate that PulD first forms a "prepore" structure that attains
      the native state via a conformational switch. 

PMID- 24019526
TI  - The deviant ATP-binding site of the multidrug efflux pump Pdr5 plays an active
      role in the transport cycle.
AB  - Pdr5 is the founding member of a large subfamily of evolutionarily distinct,
      clinically important fungal ABC transporters containing a characteristic, deviant
      ATP-binding site with altered Walker A, Walker B, Signature (C-loop), and Q-loop
      residues. In contrast to these motifs, the D-loops of the two ATP-binding sites
      have similar sequences, including a completely conserved aspartate residue.
      Alanine substitution mutants in the deviant Walker A and Signature motifs retain
      significant, albeit reduced, ATPase activity and drug resistance. The D-loop
      residue mutants D340A and D1042A showed a striking reduction in plasma membrane
      transporter levels. The D1042N mutation localized properly had nearly WT ATPase
      activity but was defective in transport and was profoundly hypersensitive to Pdr5
      substrates. Therefore, there was a strong uncoupling of ATPase activity and drug
      efflux. Taken together, the properties of the mutants suggest an additional,
      critical intradomain signaling role for deviant ATP-binding sites. 

PMID- 24019527
TI  - NEDD8 ultimate buster-1 long (NUB1L) protein promotes transfer of NEDD8 to
      proteasome for degradation through the P97UFD1/NPL4 complex.
AB  - The NEDD8 protein and neddylation levels in cells are modulated by NUB1L or NUB1
      through proteasomal degradation, but the underlying molecular mechanism is not
      well understood. Here, we report that NUB1L down-regulated the protein levels of
      NEDD8 and neddylation through specifically recognizing NEDD8 and P97/VCP. NUB1L
      directly interacted with NEDD8, but not with ubiquitin, on the key residue Asn-51
      of NEDD8 and with P97/VCP on its positively charged VCP binding motif. In
      coordination with the P97-UFD1-NPL4 complex (P97(UFD1/NPL4)), NUB1L promotes
      transfer of NEDD8 to proteasome for degradation. This mechanism is also
      exemplified by the canonical neddylation of cullin 1 for SCF (SKP1-cullin1-F-box)
      ubiquitin E3 ligases that is exquisitely regulated by the turnover of NEDD8. 

PMID- 24019528
TI  - Differential roles of C-terminal Eps15 homology domain proteins as vesiculators
      and tubulators of recycling endosomes.
AB  - Endocytic recycling involves the return of membranes and receptors to the plasma
      membrane following their internalization into the cell. Recycling generally
      occurs from a series of vesicular and tubular membranes localized to the
      perinuclear region, collectively known as the endocytic recycling compartment.
      Within this compartment, receptors are sorted into tubular extensions that later
      undergo vesiculation, allowing transport vesicles to move along microtubules and
      return to the cell surface where they ultimately undergo fusion with the plasma
      membrane. Recent studies have led to the hypothesis that the C-terminal Eps15
      homology domain (EHD) ATPase proteins are involved in the vesiculation process.
      Here, we address the functional roles of the four EHD proteins. We developed a
      novel semipermeabilized cell system in which addition of purified EHD proteins to
      reconstitute vesiculation allows us to assess the ability of each protein to
      vesiculate MICAL-L1-decorated tubular recycling endosomes (TREs). Using this
      assay, we show that EHD1 vesiculates membranes, consistent with enhanced TRE
      generation observed upon EHD1 depletion. EHD4 serves a role similar to that of
      EHD1 in TRE vesiculation, whereas EHD2, despite being capable of vesiculating
      TREs in the semipermeabilized cells, fails to do so in vivo. Surprisingly, the
      addition of EHD3 causes tubulation of endocytic membranes in our
      semipermeabilized cell system, consistent with the lack of tubulation observed
      upon EHD3 depletion. Our novel vesiculation assay and in vitro electron
      microscopy analysis, combined with in vivo data, provide evidence that the
      functions of both EHD1 and EHD4 are primarily in TRE membrane vesiculation,
      whereas EHD3 is a membrane-tubulating protein. 

PMID- 24019529
TI  - Mutational analysis identifies residues crucial for homodimerization of myeloid
      differentiation factor 88 (MyD88) and for its function in immune cells.
AB  - Myeloid differentiation factor 88 (MyD88) is an adaptor protein that transduces
      intracellular signaling pathways evoked by the Toll-like receptors (TLRs) and
      interleukin-1 receptors (IL-1Rs). MyD88 is composed of an N-terminal death domain
      (DD) and a C-terminal Toll/IL-1 receptor (TIR) domain, separated by a short
      region. Upon ligand binding, TLR/IL-1Rs hetero- or homodimerize and recruit MyD88
      through their respective TIR domains. Then, MyD88 oligomerizes via its DD and TIR
      domain and interacts with the interleukin-1 receptor-associated kinases (IRAKs)
      to form the Myddosome complex. We performed site-directed mutagenesis of
      conserved residues that are located in exposed regions of the MyD88-TIR domain
      and analyzed the effect of the mutations on MyD88 signaling. Our studies revealed
      that mutation of Glu(183), Ser(244), and Arg(288) impaired homodimerization of
      the MyD88-TIR domain, recruitment of IRAKs, and activation of NF-kappaB.
      Moreover, overexpression of two green fluorescent protein (GFP)-tagged MyD88 mini
      proteins (GFP-MyD88151-189 and GFP-MyD88168-189), comprising the Glu(183)
      residue, recapitulated these effects. Importantly, expression of these dominant
      negative MyD88 mini-proteins competed with the function of endogenous MyD88 and
      interfered with TLR2/4-mediated responses in a human monocytic cell line (THP-1)
      and in human primary monocyte-derived dendritic cells. Thus, our studies identify
      novel residues of the TIR domain that are crucially involved in MyD88
      homodimerization and TLR signaling in immune cells. 

PMID- 24019530
TI  - Structural and biochemical analyses of Mycobacterium tuberculosis N-acetylmuramyl
      L-alanine amidase Rv3717 point to a role in peptidoglycan fragment recycling.
AB  - Peptidoglycan hydrolases are key enzymes in bacterial cell wall homeostasis.
      Understanding the substrate specificity and biochemical activity of peptidoglycan
      hydrolases in Mycobacterium tuberculosis is of special interest as it can aid in
      the development of new cell wall targeting therapeutics. In this study, we report
      biochemical and structural characterization of the mycobacterial N-acetylmuramyl
      L-alanine amidase, Rv3717. The crystal structure of Rv3717 in complex with a
      dipeptide product shows that, compared with previously characterized
      peptidoglycan amidases, the enzyme contains an extra disulfide-bonded beta
      hairpin adjacent to the active site. The structure of two intermediates in
      assembly reveal that Zn(2+) binding rearranges active site residues, and
      disulfide formation promotes folding of the beta-hairpin. Although Zn(2+) is
      required for hydrolysis of muramyl dipeptide, disulfide oxidation is not required
      for activity on this substrate. The orientation of the product in the active site
      suggests a role for a conserved glutamate (Glu-200) in catalysis; mutation of
      this residue abolishes activity. The product binds at the head of a closed
      tunnel, and the enzyme showed no activity on polymerized peptidoglycan. These
      results point to a potential role for Rv3717 in peptidoglycan fragment recycling.

PMID- 24019531
TI  - Structure and biosynthesis of two exopolysaccharides produced by Lactobacillus
      johnsonii FI9785.
AB  - Exopolysaccharides were isolated and purified from Lactobacillus johnsonii
      FI9785, which has previously been shown to act as a competitive exclusion agent
      to control Clostridium perfringens in poultry. Structural analysis by NMR
      spectroscopy revealed that L. johnsonii FI9785 can produce two types of
      exopolysaccharide: EPS-1 is a branched dextran with the unusual feature that
      every backbone residue is substituted with a 2-linked glucose unit, and EPS-2 was
      shown to have a repeating unit with the following structure: -6)-alpha-Glcp-(1-3)
      beta-Glcp-(1-5)-beta-Galf-(1-6)-alpha-Glcp-(1-4)-beta-Galp-(1-4)-beta-Glcp-(1-.
      Sites on both polysaccharides were partially occupied by substituent groups: 1
      phosphoglycerol and O-acetyl groups in EPS-1 and a single O-acetyl group in EPS
      2. Analysis of a deletion mutant (DeltaepsE) lacking the putative priming
      glycosyltransferase gene located within a predicted eps gene cluster revealed
      that the mutant could produce EPS-1 but not EPS-2, indicating that epsE is
      essential for the biosynthesis of EPS-2. Atomic force microscopy confirmed the
      localization of galactose residues on the exterior of wild type cells and their
      absence in the DeltaepsE mutant. EPS2 was found to adopt a random coil structural
      conformation. Deletion of the entire 14-kb eps cluster resulted in an acapsular
      mutant phenotype that was not able to produce either EPS-2 or EPS-1. Alterations
      in the cell surface properties of the EPS-specific mutants were demonstrated by
      differences in binding of an anti-wild type L. johnsonii antibody. These findings
      provide insights into the biosynthesis and structures of novel exopolysaccharides
      produced by L. johnsonii FI9785, which are likely to play an important role in
      biofilm formation, protection against harsh environment of the gut, and
      colonization of the host. 

PMID- 24019532
TI  - Toll-like receptor 3-mediated necrosis via TRIF, RIP3, and MLKL.
AB  - Toll-like receptor (TLR) signaling is triggered by pathogen-associated molecular
      patterns that mediate well established cytokine-driven pathways, activating NF
      kappaB together with IRF3/IRF7. In addition, TLR3 drives caspase 8-regulated
      programmed cell death pathways reminiscent of TNF family death receptor
      signaling. We find that inhibition or elimination of caspase 8 during stimulation
      of TLR2, TLR3, TLR4, TLR5, or TLR9 results in receptor interacting protein (RIP)
      3 kinase-dependent programmed necrosis that occurs through either TIR domain
      containing adapter-inducing interferon-beta (TRIF) or MyD88 signal transduction.
      TLR3 or TLR4 directly activates programmed necrosis through a RIP homotypic
      interaction motif-dependent association of TRIF with RIP3 kinase (also called
      RIPK3). In fibroblasts, this pathway proceeds independent of RIP1 or its kinase
      activity, but it remains dependent on mixed lineage kinase domain-like protein
      (MLKL) downstream of RIP3 kinase. Here, we describe two small molecule RIP3
      kinase inhibitors and employ them to demonstrate the common requirement for RIP3
      kinase in programmed necrosis induced by RIP1-RIP3, DAI-RIP3, and TRIF-RIP3
      complexes. Cell fate decisions following TLR signaling parallel death receptor
      signaling and rely on caspase 8 to suppress RIP3-dependent programmed necrosis
      whether initiated directly by a TRIF-RIP3-MLKL pathway or indirectly via TNF
      activation and the RIP1-RIP3-MLKL necroptosis pathway. 

PMID- 24019533
TI  - Phosphatidylserine flipping enhances membrane curvature and negative charge
      required for vesicular transport.
AB  - Vesicle-mediated protein transport between organelles of the secretory and
      endocytic pathways is strongly influenced by the composition and organization of
      membrane lipids. In budding yeast, protein transport between the trans-Golgi
      network (TGN) and early endosome (EE) requires Drs2, a phospholipid translocase
      in the type IV P-type ATPase family. However, downstream effectors of Drs2 and
      specific phospholipid substrate requirements for protein transport in this
      pathway are unknown. Here, we show that the Arf GTPase-activating protein
      (ArfGAP) Gcs1 is a Drs2 effector that requires a variant of the ArfGAP lipid
      packing sensor (+ALPS) motif for localization to TGN/EE membranes. Drs2 increases
      membrane curvature and anionic phospholipid composition of the cytosolic leaflet,
      both of which are sensed by the +ALPS motif. Using mutant forms of Drs2 and the
      related protein Dnf1, which alter their ability to recognize phosphatidylserine,
      we show that translocation of this substrate to the cytosolic leaflet is
      essential for +ALPS binding and vesicular transport between the EE and the TGN. 

PMID- 24019534
TI  - Rap1 potentiates endothelial cell junctions by spatially controlling myosin II
      activity and actin organization.
AB  - Reorganization of the actin cytoskeleton is responsible for dynamic regulation of
      endothelial cell (EC) barrier function. Circumferential actin bundles (CAB)
      promote formation of linear adherens junctions (AJs) and tightening of EC
      junctions, whereas formation of radial stress fibers (RSF) connected to punctate
      AJs occurs during junction remodeling. The small GTPase Rap1 induces CAB
      formation to potentiate EC junctions; however, the mechanism underlying Rap1
      induced CAB formation remains unknown. Here, we show that myotonic dystrophy
      kinase-related CDC42-binding kinase (MRCK)-mediated activation of non-muscle
      myosin II (NM-II) at cell-cell contacts is essential for Rap1-induced CAB
      formation. Our data suggest that Rap1 induces FGD5-dependent Cdc42 activation at
      cell-cell junctions to locally activate the NM-II through MRCK, thereby inducing
      CAB formation. We further reveal that Rap1 suppresses the NM-II activity
      stimulated by the Rho-ROCK pathway, leading to dissolution of RSF. These findings
      imply that Rap1 potentiates EC junctions by spatially controlling NM-II activity
      through activation of the Cdc42-MRCK pathway and suppression of the Rho-ROCK
      pathway. 

PMID- 24019535
TI  - SnoN facilitates ALK1-Smad1/5 signaling during embryonic angiogenesis.
AB  - In endothelial cells, two type I receptors of the transforming growth factor beta
      (TGF-beta) family, ALK1 and ALK5, coordinate to regulate embryonic angiogenesis
      in response to BMP9/10 and TGF-beta. Whereas TGF-beta binds to and activates
      ALK5, leading to Smad2/3 phosphorylation and inhibition of endothelial cell
      proliferation and migration, BMP9/10 and TGF-beta also bind to ALK1, resulting in
      the activation of Smad1/5. SnoN is a negative regulator of ALK5 signaling through
      the binding and repression of Smad2/3. Here we uncover a positive role of SnoN in
      enhancing Smad1/5 activation in endothelial cells to promote angiogenesis. Upon
      ligand binding, SnoN directly bound to ALK1 on the plasma membrane and
      facilitated the interaction between ALK1 and Smad1/5, enhancing Smad1/5
      phosphorylation. Disruption of this SnoN-Smad interaction impaired Smad1/5
      activation and up-regulated Smad2/3 activity. This resulted in defective
      angiogenesis and arteriovenous malformations, leading to embryonic lethality at
      E12.5. Thus, SnoN is essential for TGF-beta/BMP9-dependent biological processes
      by its ability to both positively and negatively modulate the activities of Smad
      dependent pathways. 

PMID- 24019536
TI  - RCP-driven alpha5beta1 recycling suppresses Rac and promotes RhoA activity via
      the RacGAP1-IQGAP1 complex.
AB  - Inhibition of alphavbeta3 or expression of mutant p53 promotes invasion into
      fibronectin (FN)-containing extracellular matrix (ECM) by enhancing Rab-coupling
      protein (RCP)-dependent recycling of alpha5beta1 integrin. RCP and alpha5beta1
      cooperatively recruit receptor tyrosine kinases, including EGFR1, to regulate
      their trafficking and downstream signaling via protein kinase B (PKB)/Akt, which,
      in turn, promotes invasive migration. In this paper, we identify a novel PKB/Akt
      substrate, RacGAP1, which is phosphorylated as a consequence of RCP-dependent
      alpha5beta1 trafficking. Phosphorylation of RacGAP1 promotes its recruitment to
      IQGAP1 at the tips of invasive pseudopods, and RacGAP1 then locally suppresses
      the activity of the cytoskeletal regulator Rac and promotes the activity of RhoA
      in this subcellular region. This Rac to RhoA switch promotes the extension of
      pseudopodial processes and invasive migration into FN-containing matrices, in a
      RhoA-dependent manner. Thus, the localized endocytic trafficking of alpha5beta1
      within the tips of invasive pseudopods elicits signals that promote the
      reorganization of the actin cytoskeleton, protrusion, and invasion into FN-rich
      ECM. 

PMID- 24019537
TI  - M2-like macrophages are responsible for collagen degradation through a mannose
      receptor-mediated pathway.
AB  - Tissue remodeling processes critically depend on the timely removal and
      remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related
      to the turnover of this abundant extracellular matrix component in vivo are still
      incompletely understood. We therefore took advantage of recent advances in
      optical imaging to develop an assay to visualize collagen turnover in situ and
      identify cell types and molecules involved in this process. Collagen introduced
      into the dermis of mice underwent cellular endocytosis in a partially matrix
      metalloproteinase-dependent manner and was subsequently routed to lysosomes for
      complete degradation. Collagen uptake was predominantly executed by a
      quantitatively minor population of M2-like macrophages, whereas more abundant
      Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized
      collagen at lower levels. Genetic ablation of the collagen receptors mannose
      receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein
      (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This
      study demonstrates the importance of receptor-mediated cellular uptake to
      collagen turnover in vivo and identifies a key role of M2-like macrophages in
      this process. 

PMID- 24019538
TI  - aPKClambda controls epidermal homeostasis and stem cell fate through regulation
      of division orientation.
AB  - The atypical protein kinase C (aPKC) is a key regulator of polarity and cell fate
      in lower organisms. However, whether mammalian aPKCs control stem cells and fate
      in vivo is not known. Here we show that loss of aPKClambda in a self-renewing
      epithelium, the epidermis, disturbed tissue homeostasis, differentiation, and
      stem cell dynamics, causing progressive changes in this tissue. This was
      accompanied by a gradual loss of quiescent hair follicle bulge stem cells and a
      temporary increase in proliferating progenitors. Lineage tracing analysis showed
      that loss of aPKClambda altered the fate of lower bulge/hair germ stem cells.
      This ultimately led to loss of proliferative potential, stem cell exhaustion,
      alopecia, and premature aging. Inactivation of aPKClambda produced more
      asymmetric divisions in different compartments, including the bulge. Thus,
      aPKClambda is crucial for homeostasis of self-renewing stratifying epithelia, and
      for the regulation of cell fate, differentiation, and maintenance of epidermal
      bulge stem cells likely through its role in balancing symmetric and asymmetric
      division. 

PMID- 24019540
TI  - Revealed in the wound.

PMID- 24019539
TI  - Prognostic impact of deficient DNA mismatch repair in patients with stage III
      colon cancer from a randomized trial of FOLFOX-based adjuvant chemotherapy.
AB  - PURPOSE: The association of deficient DNA mismatch repair (dMMR) with prognosis
      in patients with colon cancer treated with adjuvant fluorouracil, leucovorin, and
      oxaliplatin (FOLFOX) chemotherapy remains unknown. PATIENTS AND METHODS:
      Resected, stage III colon carcinomas from patients (N = 2,686) randomly assigned
      to FOLFOX +/- cetuximab (North Central Cancer Treatment Group N0147 trial) were
      analyzed for mismatch repair (MMR) protein expression and mutations in
      BRAF(V600E) (exon 15) and KRAS (codons 12 and 13). Association of biomarkers with
      disease-free survival (DFS) was determined using Cox models. A validation cohort
      (Cancer and Leukemia Group B 88903 trial) was used. RESULTS: dMMR was detected in
      314 (12%) of 2,580 tumors, of which 49.3% and 10.6% had BRAF(V600E) or KRAS
      mutations, respectively. MMR status was not prognostic overall (adjusted hazard
      ratio [HR], 0.82; 95% CI, 0.64 to 1.07; P = .14), yet significant interactions
      were found between MMR and primary tumor site (P(interaction) = .009) and lymph
      node category (N1 v N2; P(interaction) = .014). Favorable DFS was observed for
      dMMR versus proficient MMR proximal tumors (HR, 0.71; 95% CI, 0.53 to 0.94; P =
      .018) but not dMMR distal tumors (HR, 1.71; 95% CI, 0.99 to 2.95; P = .056),
      adjusting for mutations and covariates. Any survival benefit of dMMR was lost in
      N2 tumors. Mutations in BRAF(V600E) (HR, 1.37; 95% CI, 1.08 to 1.70; P = .009) or
      KRAS (HR, 1.44; 95% CI, 1.21 to 1.70; P < .001) were independently associated
      with worse DFS. The observed MMR by tumor site interaction was validated in an
      independent cohort of stage III colon cancers (P(interaction) = .037).
      CONCLUSION: The prognostic impact of MMR depended on tumor site, and this
      interaction was validated in an independent cohort. Among dMMR cancers, proximal
      tumors had favorable outcome, whereas distal or N2 tumors had poor outcome. BRAF
      or KRAS mutations were independently associated with adverse outcome.

PMID- 24019542
TI  - Hospice and where the doctor can be.

PMID- 24019543
TI  - Preserving the sanctity of overall survival for drugs approved on the basis of
      progression-free survival: tivozanib as a case study.

PMID- 24019544
TI  - Phase Ib study of panobinostat and bortezomib in relapsed or relapsed and
      refractory multiple myeloma.
AB  - PURPOSE: Despite advancements, prognosis for patients with relapsed/refractory
      multiple myeloma (MM) is poor, and novel therapies are needed. Panobinostat is a
      potent deacetylase inhibitor that elicits synergistic effects on MM cells in
      combination with bortezomib. This phase Ib study sought to determine the maximum
      tolerated dose (MTD) of panobinostat plus bortezomib in patients with relapsed or
      relapsed and refractory MM. PATIENTS AND METHODS: In the dose-escalation phase (n
      = 47), panobinostat was administered orally thrice weekly every week in
      combination with bortezomib (21-day cycles). After MTD determination, patients
      were evaluated in an expansion phase (n = 15) that incorporated a 1-week
      treatment holiday of panobinostat, with dexamethasone added in cycle 2.
      Additional assessments included safety, pharmacokinetics, and efficacy per
      International Myeloma Working Group criteria. RESULTS: The MTD was established at
      panobinostat 20 mg plus bortezomib 1.3 mg/m(2). Grade 3 or 4 adverse events (AEs)
      included thrombocytopenia (85.1%), neutropenia (63.8%), and asthenia (29.8%) in
      the escalation phase, and thrombocytopenia (66.7%), neutropenia (46.7%), and
      fatigue (20.0%) in the expansion phase. At MTD in the escalation phase, eight
      patients (47.1%) discontinued therapy as a result of AEs, whereas five patients
      (33.3%) discontinued treatment in the expansion phase. Expansion phase patients
      demonstrated greater median treatment duration. Overall response rate (ORR) was
      73.3% in the expansion phase and 52.9% at the escalation phase MTD. Among
      bortezomib-refractory patients, the ORR was 26.3%, and 42.1% of patients had >=
      minimal response. CONCLUSION: The MTD of panobinostat plus bortezomib was
      determined and demonstrated activity in patients with relapsed or
      relapsed/refractory MM, including bortezomib-refractory patients. A phase II/III
      clinical trial program (Panobinostat or Placebo With Bortezomib and Dexamethasone
      in Patients With Relapsed Multiple Myeloma [PANORAMA]) has been initiated.

PMID- 24019546
TI  - Long-term outcomes after pelvic radiation for early-stage endometrial cancer.
AB  - PURPOSE: This follow-up of a randomized study was conducted to assess the long
      term effects of external beam radiation therapy (EBRT) in the adjuvant treatment
      of early-stage endometrial cancer. PATIENTS AND METHODS: Between 1968 and 1974,
      568 patients with stage I endometrial cancer were included. After primary
      surgery, patients were randomly assigned to either vaginal radium brachytherapy
      followed by EBRT (n = 288) or brachytherapy alone (n = 280). Overall survival was
      analyzed by using the Kaplan-Meier method. A Cox proportional hazards model was
      used to estimate hazard ratios (HRs) with 95% CIs. We also conducted analyses
      stratified by age groups. RESULTS: After median 20.5 years (range, 0 to 43.4
      years) of follow-up, no statistically significant difference was revealed in
      overall survival (P = .186) between treatment groups. However, women younger than
      age 60 years had significantly higher mortality rates after EBRT (HR, 1.36; 95%
      CI, 1.06 to 1.76) than the control group. The risk of secondary cancer increased
      after EBRT, especially in women younger than age 60 years (HR, 2.02; 95% CI, 1.30
      to 3.15). CONCLUSION: We observed no survival benefit of external pelvic
      radiation in early-stage endometrial carcinoma. In women younger than age 60
      years, pelvic radiation decreased survival and increased the risk of secondary
      cancer. Adjuvant EBRT should be used with caution, especially in women with a
      long life expectancy.

PMID- 24019545
TI  - Tivozanib versus sorafenib as initial targeted therapy for patients with
      metastatic renal cell carcinoma: results from a phase III trial.
AB  - PURPOSE: Tivozanib is a potent and selective tyrosine kinase inhibitor of
      vascular endothelial growth factor receptor 1 (VEGFR1), -2, and -3. This phase
      III trial compared tivozanib with sorafenib as initial targeted therapy in
      patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS:
      Patients with metastatic RCC, with a clear cell component, prior nephrectomy,
      measurable disease, and 0 or 1 prior therapies for metastatic RCC were randomly
      assigned to tivozanib or sorafenib. Prior VEGF-targeted therapy and mammalian
      target of rapamycin inhibitor were not permitted. The primary end point was
      progression-free survival (PFS) by independent review. RESULTS: A total of 517
      patients were randomly assigned to tivozanib (n = 260) or sorafenib (n = 257).
      PFS was longer with tivozanib than with sorafenib in the overall population
      (median, 11.9 v 9.1 months; hazard ratio [HR], 0.797; 95% CI, 0.639 to 0.993; P =
      .042). One hundred fifty-six patients (61%) who progressed on sorafenib crossed
      over to receive tivozanib. The final overall survival (OS) analysis showed a
      trend toward longer survival on the sorafenib arm than on the tivozanib arm
      (median, 29.3 v 28.8 months; HR, 1.245; 95% CI, 0.954 to 1.624; P = .105).
      Adverse events (AEs) more common with tivozanib than with sorafenib were
      hypertension (44% v 34%) and dysphonia (21% v 5%). AEs more common with sorafenib
      than with tivozanib were hand-foot skin reaction (54% v 14%) and diarrhea (33% v
      23%). CONCLUSION: Tivozanib demonstrated improved PFS, but not OS, and a
      differentiated safety profile, compared with sorafenib, as initial targeted
      therapy for metastatic RCC.

PMID- 24019547
TI  - Reply to M.R. Litzow et al.

PMID- 24019548
TI  - Emil Frei III, 1924-2013.

PMID- 24019549
TI  - End points and trial design in geriatric oncology research: a joint European
      organisation for research and treatment of cancer--Alliance for Clinical Trials
      in Oncology--International Society Of Geriatric Oncology position article.
AB  - Selecting the most appropriate end points for clinical trials is important to
      assess the value of new treatment strategies. Well-established end points for
      clinical research exist in oncology but may not be as relevant to the older
      cancer population because of competing risks of death and potentially increased
      impact of therapy on global functioning and quality of life. This article
      discusses specific clinical end points and their advantages and disadvantages for
      older individuals. Randomized or single-arm phase II trials can provide insight
      into the range of efficacy and toxicity in older populations but ideally need to
      be confirmed in phase III trials, which are unfortunately often hindered by the
      severe heterogeneity of the older cancer population, difficulties with selection
      bias depending on inclusion criteria, physician perception, and barriers in
      willingness to participate. All clinical trials in oncology should be without an
      upper age limit to allow entry of eligible older adults. In settings where so
      called standard therapy is not feasible, specific trials for older patients with
      cancer might be required, integrating meaningful measures of outcome. Not all
      questions can be answered in randomized clinical trials, and large observational
      cohort studies or registries within the community setting should be established
      (preferably in parallel to randomized trials) so that treatment patterns across
      different settings can be compared with impact on outcome. Obligatory integration
      of a comparable form of geriatric assessment is recommended in future studies,
      and regulatory organizations such as the European Medicines Agency and US Food
      and Drug Administration should require adequate collection of data on efficacy
      and toxicity of new drugs in fit and frail elderly subpopulations. 

PMID- 24019550
TI  - Sentinel node mapping for gastric cancer: a prospective multicenter trial in
      Japan.
AB  - PURPOSE: Complicated gastric lymphatic drainage potentially undermines the
      utility of sentinel node (SN) biopsy in patients with gastric cancer. Encouraged
      by several favorable single-institution reports, we conducted a multicenter,
      single-arm, phase II study of SN mapping that used a standardized dual tracer
      endoscopic injection technique. PATIENTS AND METHODS: Patients with previously
      untreated cT1 or cT2 gastric adenocarcinomas < 4 cm in gross diameter were
      eligible for inclusion in this study. SN mapping was performed by using a
      standardized dual tracer endoscopic injection technique. Following biopsy of the
      identified SNs, mandatory comprehensive D2 or modified D2 gastrectomy was
      performed according to current Japanese Gastric Cancer Association guidelines.
      RESULTS: Among 433 patients who gave preoperative consent, 397 were deemed
      eligible on the basis of surgical findings. SN biopsy was performed in all
      patients, and the SN detection rate was 97.5% (387 of 397). Of 57 patients with
      lymph node metastasis by conventional hematoxylin and eosin staining, 93% (53 of
      57) had positive SNs, and the accuracy of nodal evaluation for metastasis was 99%
      (383 of 387). Only four false-negative SN biopsies were observed, and pathologic
      analysis revealed that three of those biopsies were pT2 or tumors > 4 cm. We
      observed no serious adverse effects related to endoscopic tracer injection or the
      SN mapping procedure. CONCLUSION: The endoscopic dual tracer method for SN biopsy
      was confirmed as safe and effective when applied to the superficial, relatively
      small gastric adenocarcinomas included in this study.

PMID- 24019551
TI  - Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection
      of primary tumor > 1.5 mm in patients with stage II melanoma: results of the
      EORTC 18961 randomized phase III trial.
AB  - PURPOSE: The GM2 ganglioside is an antigen expressed in the majority of
      melanomas. The GM2-KLH/QS-21 vaccine induces high immunoglobulin M (IgM) and IgG
      antibody responses. The EORTC 18961 trial compared the efficacy of GM2-KLH/QS-21
      vaccination versus observation. PATIENTS AND METHODS: A total of 1,314 patients
      with a primary tumor > 1.50 mm in thickness (T3-4N0M0; American Joint Committee
      on Cancer stage II) were randomly assigned to GM2-KLH/QS-21 vaccination (n = 657)
      or observation (n = 657). Treatment consisted of subcutaneous injections once per
      week from week 1 to 4, then every 3 months for the first 2 years and every 6
      months during the third year. Primary end point was relapse-free survival (RFS).
      Secondary end points were distant metastasis-free survival (DMFS) and overall
      survival (OS). Analyses were by intent to treat. RESULTS: After a median follow
      up of 1.8 years, the trial was stopped at the second interim analysis for
      futility regarding RFS (hazard ratio [HR], 1.00; P = .99) and detrimental outcome
      regarding OS (HR, 1.66; P = .02). After a median follow-up of 4.2 years, we had
      recorded 400 relapses, nine deaths without relapse, a total of 236 deaths. At 4
      years, the vaccination arm showed a decreased RFS rate of 1.2% (HR, 1.03; 95% CI,
      0.84 to 1.25) and OS rate of 2.1% (HR, 1.16; 95% CI, 0.90 to 1.51). Toxicity was
      acceptable, with 4.6% of patients ending study participation because of toxicity.
      CONCLUSION: GM2-KLH/QS-21 vaccination does not improve outcome for patients with
      stage II melanoma.

PMID- 24019552
TI  - Intestinal lamina propria dendritic cells maintain T cell homeostasis but do not
      affect commensalism.
AB  - Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two
      CD103(+) subsets that differ in CD11b expression. We report here that Langerin is
      expressed by human LP DCs and that transgenic human langerin drives expression in
      CD103(+)CD11b(+) LP DCs in mice. This subset was ablated in huLangerin-DTA mice,
      resulting in reduced LP Th17 cells without affecting Th1 or T reg cells. Notably,
      cognate DC-T cell interactions were not required for Th17 development, as this
      response was intact in huLangerin-Cre I-Abeta(fl/fl) mice. In contrast, responses
      to intestinal infection or flagellin administration were unaffected by the
      absence of CD103(+)CD11b(+) DCs. huLangerin-DTA x BatF3(-/-) mice lacked both
      CD103(+) LP DC subsets, resulting in defective gut homing and fewer LP T reg
      cells. Despite these defects in LP DCs and resident T cells, we did not observe
      alterations of intestinal microbial communities. Thus, CD103(+) LP DC subsets
      control T cell homeostasis through both nonredundant and overlapping mechanisms. 

PMID- 24019553
TI  - Targeting antigens to CD180 rapidly induces antigen-specific IgG, affinity
      maturation, and immunological memory.
AB  - Antigen (Ag) targeting is an efficient way to induce immune responses. Ag is
      usually coupled to an antibody (Ab) specific for a receptor expressed on
      dendritic cells (DCs), and then the Ag-anti-receptor is inoculated with an
      adjuvant. Here we report that targeting Ag to a receptor expressed on both B
      cells and DCs, the TLR orphan receptor CD180, in the absence of adjuvant rapidly
      induced IgG responses that were stronger than those induced by Ag in alum. Ag
      conjugated to anti-CD180 (Ag-alphaCD180) induced affinity maturation and Ab
      responses that were partially T cell independent, as Ag-specific IgGs were
      generated in CD40- and T cell-deficient mice. After preimmunization with Ag
      alphaCD180 and boosting with soluble Ag, both WT and CD40 knockout (KO) mice
      rapidly produced Ag-specific IgG-forming cells, demonstrating that Ag-anti-CD180
      induces immunological memory. The potent adjuvant effect of Ag-alphaCD180
      required Ag to be coupled to anti-CD180 and the responsive B cells to express
      both CD180 and an Ag-specific B cell receptor. Surprisingly, CD180 Ag targeting
      also induced IgG Abs in BAFF-R KO mice lacking mature B cells and in mice
      deficient in interferon signaling. Targeting Ag to CD180 may be useful for
      therapeutic vaccination and for vaccinating the immune compromised. 

PMID- 24019554
TI  - Epidermal IL-15Ralpha acts as an endogenous antagonist of psoriasiform
      inflammation in mouse and man.
AB  - Stromal cells at epithelial surfaces contribute to innate immunity by sensing
      environmental danger signals and producing proinflammatory cytokines. However,
      the role of stromal cells in controlling local inflammation is unknown. We show
      that endogenous soluble IL-15 receptor alpha (IL-15Ralpha) derived from epidermal
      stroma, notably keratinocytes, protects against dendritic cell/IL-15-mediated, T
      cell-driven skin inflammation in vivo, and is relevant to human psoriasis.
      Selective lack of IL-15Ralpha on stromal epidermal cells exacerbated psoriasiform
      inflammation in animals. Epidermal IL-15Ralpha was shed by keratinocytes via
      proteolytic cleavage by matrix metalloproteinases upon stimulation with
      proinflammatory cytokines to counteract IL-15-induced proliferation of IL-17(+)
      alphabeta and gammadelta T cells and production of TNF, IL-23, IL-17, and IL-22
      during skin inflammation. Notably, administration of soluble IL-15Ralpha was able
      to repress secretion of IL-1beta, IL-6, and TNF by keratinocytes, dampen
      expansion of IL-17(+) alphabeta and gammadelta T cells in vivo, and prevent
      psoriasis in two mouse models, including human xenograft AGR mice. Serum levels
      of soluble IL-15Ralpha negatively correlated with disease severity, and levels
      rose upon successful treatment of psoriasis in patients. Thus, stressed epidermal
      stromal cells use soluble IL-15Ralpha to dampen chronic inflammatory skin
      disease. 

PMID- 24019555
TI  - Do Early Literacy Skills in Children's First Language Promote Development of
      Skills in Their Second Language? An Experimental Evaluation of Transfer.
AB  - The purpose of this study was to evaluate the cross-language transfer of the
      emergent literacy skills of preschoolers who were Spanish-speaking language
      minority children in the context of an experimental intervention study. Ninety
      four children were randomly assigned to either a control condition (High/Scope
      preschool curriculum) or to receive small-group pull-out instruction (Literacy
      Express Preschool Curriculum) in English or initially in Spanish and
      transitioning to English. We examined whether children's initial skills in one
      language moderated the impact of the intervention on those same skills in the
      other language at posttest. Results demonstrated that, for children in the
      English-only intervention condition, initial Spanish receptive vocabulary and
      elision skills moderated the impact of the intervention on English receptive
      vocabulary and elision skills at posttest, respectively. For children in the
      transitional intervention condition, initial English definitional vocabulary and
      elision skills moderated the impact of the intervention on Spanish definitional
      vocabulary and elision skills at posttest, respectively. Results for the
      vocabulary interactions, as well as the elision interaction for the English-only
      intervention group comparisons, supported the notion of transfer of specific
      linguistic information across languages. Results for elision interaction for the
      transitional intervention group comparisons supported language-independent
      transfer. Implications for the theory of cross-language transfer of emergent
      literacy skills are discussed.

PMID- 24019556
TI  - Diversity and Convergence of Sodium Channel Mutations Involved in Resistance to
      Pyrethroids.
AB  - Pyrethroid insecticides target voltage-gated sodium channels, which are critical
      for electrical signaling in the nervous system. The intensive use of pyrethroids
      in controlling arthropod pests and disease vectors has led to many instances of
      pyrethroid resistance around the globe. In the past two decades, studies have
      identified a large number of sodium channel mutations that are associated with
      resistance to pyrethroids. The purpose of this review is to summarize both common
      and unique sodium channel mutations that have been identified in arthropod pests
      of importance to agriculture or human health. Identification of these mutations
      provides valuable molecular markers for resistance monitoring in the field and
      helped the discovery of the elusive pyrethroid receptor site(s) on the sodium
      channel.

PMID- 24019558
TI  - Parental Spanking and Subsequent Risk for Child Aggression in Father-Involved
      Families of Young Children.
AB  - This study examined separate and combined maternal and paternal use of spanking
      with children at age 3 and children's subsequent aggressive behavior at age 5.
      The sample was derived from a birth cohort study and included families (n = 923)
      in which both parents lived with the child at age 3. In this sample, 44% of 3
      year-olds were spanked 2 times or more in the past month by either parent or both
      parents. In separate analyses, being spanked more than twice in the prior month
      at age 3, by either mother or father, was associated with increased child
      aggression at 5 years. In combined analyses, there was a dose-response
      association; the greatest risk for child aggression was reported when both
      parents spanked more than twice in the prior month (adjusted odds ratio: 2.01;
      [confidence interval: 1.03-3.94]). Violence prevention initiatives should target
      and engage mothers and fathers in anticipatory guidance efforts aimed at
      increasing the use of effective and non-aggressive child discipline techniques
      and reducing the use of spanking.

PMID- 24019560
TI  - Enhancement of transdermal penetration and bioavailability of poorly soluble
      acyclovir using solid lipid nanoparticles incorporated in gel cream.
AB  - The objective of this work was to increase the amount of acyclovir in the basal
      epidermis, site of herpes virus simplex infection, using the solid lipid
      nanoparticles loaded gel cream as carriers. Solid lipid nanoparticles were
      prepared by high pressure homogenisation method and incorporated in a semisolid
      submicron gel cream. Acyclovir distribution into rat skin after topical
      application of solid lipid nanoparticles loaded gel cream was determined by
      fabricated Franz diffusion cell. The results showed that, the quantity of the
      acyclovir in the basal epidermis with the solid lipid nanoparticles loaded
      submicron gel cream was two folds times more than marketed acyclovir gel cream.
      This type of carrier can improve acyclovir loaded therapy since it increases drug
      retention in the basal epidermis. 

PMID- 24019557
TI  - MRI findings of elevated intracranial pressure in cerebral venous thrombosis
      versus idiopathic intracranial hypertension with transverse sinus stenosis.
AB  - PURPOSE: To determine whether MRI signs suggesting elevated intracranial pressure
      (ICP) are preferentially found in patients with idiopathic intracranial
      hypertension (IIH) than in those with cerebral venous thrombosis (CVT). METHODS:
      Among 240 patients who underwent standardized contrast-enhanced brain MRI/MRV at
      our institution between 9/2009 and 9/2011, 60 with abnormal imaging findings on
      MRV were included: 27 patients with definite IIH, 2 patients with presumed IIH,
      and 31 with definite CVT. Medical records were reviewed, and imaging studies were
      prospectively evaluated by the same neuroradiologist to assess for presence or
      absence of transverse sinus stenosis (TSS), site of CVT if present, posterior
      globe flattening, optic nerve sheath dilation/tortuosity, and the size/appearance
      of the sella turcica. RESULTS: 29 IIH patients (28 women, 19 black, median-age
      28, median-body mass index, 34) had bilateral TSS. 31 CVT patients (19 women, 13
      black, median-age 46, median-BMI 29) had thrombosis of the sagittal (3), sigmoid
      (3), cavernous (1), unilateral transverse (7), or multiple (16) sinuses or
      cortical veins (1). Empty/partially-empty sellae were more common in IIH (3/29
      and 24/29) than in CVT patients (1/31 and 19/31) (p<0.001). Flattening of the
      globes and dilation/tortuosity of the optic nerve sheaths were more common in IIH
      (20/29 and 18/29) than in CVT patients (13/31 and 5/31) (p<0.04). CONCLUSION:
      Although abnormal imaging findings suggestive of raised ICP are more common in
      IIH, they are not specific for IIH and are found in patients with raised ICP from
      other causes such as CVT.

PMID- 24019559
TI  - Leech therapeutic applications.
AB  - Hematophagous animals including leeches have been known to possess biologically
      active compounds in their secretions, especially in their saliva. The blood
      sucking annelids, leeches have been used for therapeutic purposes since the
      beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians
      used leeches for a wide range of diseases starting from the conventional use for
      bleeding to systemic ailments, such as skin diseases, nervous system
      abnormalities, urinary and reproductive system problems, inflammation, and dental
      problems. Recently, extensive researches on leech saliva unveiled the presence of
      a variety of bioactive peptides and proteins involving antithrombin (hirudin,
      bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin),
      antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a
      comeback as a new remedy for many chronic and life-threatening abnormalities,
      such as cardiovascular problems, cancer, metastasis, and infectious diseases. In
      the 20(th) century, leech therapy has established itself in plastic and
      microsurgery as a protective tool against venous congestion and served to salvage
      the replanted digits and flaps. Many clinics for plastic surgery all over the
      world started to use leeches for cosmetic purposes. Despite the efficacious
      properties of leech therapy, the safety, and complications of leeching are still
      controversial. 

PMID- 24019561
TI  - Preparation and In vitro Evaluation of Naproxen Suppositories.
AB  - The aim of this work was to develop the best formulations for naproxen
      suppositories. The effects of different bases and surfactants on the
      physicochemical characteristics of the suppositories were determined by several
      tests such as weight variation, melting point, assay, hardness, and release rate.
      All formulations met the standard criteria for tested physicochemical parameters;
      weight variation (97-112%), content uniformity (97-105%), melting point (4.66-8.7
      min) and hardness tests (>5400 g). Based on release rate studies, hydrophilic,
      and lipophilic bases without surfactants were not suitable bases for naproxen
      suppository. Amongst the formulations containing surfactants only Witepsol H15
      with 0.5% w/w of Tween 80 and Witepsol W35 with 0.5% of cetylpyridinium chloride
      were suitable and released nearly complete drug during 30 and 60 min,
      respectively. This study demonstrates the effects of incorporation of known
      agents on the in vitro release characteristics of naproxen suppository. 

PMID- 24019562
TI  - Antiulcerogenic effect of gallic Acid in rats and its effect on oxidant and
      antioxidant parameters in stomach tissue.
AB  - In the present study, we investigate the antiulcerogenic effect of gallic acid
      against aspirin plus pyrolus ligation-induced gastric ulcer in rats. Rats were
      treated with gallic acid (100 and 200 mg/kg) and famotidine (20 mg/kg) for 1
      week, followed by induction of gastric ulcer using the aspirin plus pyrolus
      ligation model. At the end of 4 h after ligation, the rats were sacrificed and
      ulcer index, gastric juice volume, pH and other biochemical parameter of gastric
      juice were evaluated. Stomachs of rats were evaluated biochemically to determine
      oxidant and antioxidant parameters. Pretreatment with gallic acid significantly
      decreased ulcer index, gastric juice volume, free and total acidity, total
      protein, DNA content and increased pH and carbohydrates concentration. Gallic
      acid at a dose of 100 and 200 mg/kg exerted 69.7 and 78.9% ulcer inhibition,
      respectively. The levels of superoxide dismutase, catalase, reduced glutathione,
      glutathione reductase, glutathione peroxidise, glucose-6-phosphate dehydrogenase
      were increased while reduction in myeloperoxidase and lipid peroxidation were
      observed in the stomach tissues of the drug treated rats. The histopathological
      studies further confirmed the antiulcer activity of gallic acid. We conclude that
      the gallic acid possesses antiulcer effect and that these occur by a mechanism
      that involves attenuation of offensive factors, improvement of mucosal defensive
      with activation of antioxidant parameters and inhibition of some toxic oxidant
      parameters. 

PMID- 24019563
TI  - Evaluation of Antimicrobial and Wound Healing Potentials of Ethanol Extract of
      Wedelia biflora Linn D.C. Leaves.
AB  - To rationalize scientifically the traditional claim on use of Wedelia biflora
      (Linn.) D. C. for the treatment of wounds and infections, the present study was
      designed to evaluate the antimicrobial and wound healing activity of ethanol
      extract of leaves of W. biflora. In in vitro assays the test extract was
      subjected to antimicrobial activity by agar well-diffusion method and minimum
      inhibitory concentration method in different microbial strains. Wound healing
      activity of the test extract was studied by excision wound model and incision
      wound model in Wistar albino rats. In excision wound model, 97.90% wound healing
      was recorded in 10% w/w extract treated group on 16(th) days of postsurgery,
      whereas only 58.50% was observed in control group. In incision model, higher
      breaking strength, high hydroxyl proline content and histopathological study in
      extract treated groups revealed higher collagen redeposition than the control
      group. The agar well-diffusion evaluation and minimum inhibitory concentration
      established antimicrobial efficacy of ethanol extracts of W. biflora. These
      observations established the traditional claim and therapeutic activity of W.
      biflora and it could be a potent wound healing candidate for use in future. 

PMID- 24019564
TI  - Synthesis of conjugated chitosan and its effect on drug permeation from
      transdermal patches.
AB  - The aim of this study was to synthesis the conjugated chitosan by covalent
      attachment of thiol moieties to the cationic polymer, mediated by a carbodiimide
      to improve permeation properties of chitosan. Thioglycolic acid was covalently
      attached to chitosan by the formation of amide bonds between the primary amino
      groups of the polymer and the carboxylic acid groups of thioglycolic acid. Hence,
      these polymers are called as thiomers or thiolated polymers. Conjugation of
      chitosan was confirmed by Fourier transform-infrared and differential scanning
      calorimetric analysis. Matrix type transdermal patches of carvedilol were
      prepared using the different proportions of chitosan and chitosan-thioglycolic
      acid conjugates (2:0, 1.7:0.3, 1.4:0.6, 1:1, 0.6:1.4 and 0.3:1.7) by solvent
      casting technique. Prepared matrix type patches were evaluated for their
      physicochemical characterization followed by in vitro evaluation. Selected
      formulations were subjected for their ex vivo studies on Wistar albino rat skin
      and human cadaver skin using the modified Franz diffusion cell. As the proportion
      of conjugated chitosan increased, the transdermal patches showed increased drug
      permeation. The mechanism of drug release was found to be nonFickian profiles.
      The present study concludes that the transdermal patches of carvedilol using
      conjugated chitosan with different proportions of chitosan were successfully
      developed to provide improved drug permeation. The transdermal patches can be a
      good approach to improve drug bioavailability by bypassing the extensive hepatic
      first-pass metabolism of the drug. 

PMID- 24019565
TI  - Influence of Circulation System on Estimation of Absorption and Elimination
      Constant after per oral Drug Administration: A Reanalysis.
AB  - This study aimed to identify the cause of atypical shape of measured
      concentration-time profile in the peak area by one compartment open model with a
      lag time (Bateman function with a lag) after single dose oral administration of
      drug published in "Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts
      and Application" by Gabrielsson and Weiner (1997) and two concentration profiles
      after frequent sampling oral glucose tolerance test. Following the oral
      administration of 100 MUg of substance A to human volunteer, frequent sampling
      was carried out and concentration-time profiles were obtained. Our hemodynamic
      circulatory structural model capable of parameters estimation of circulation and
      gastrointestinal subsystem to explain the plateau within the interval 40-100 min
      (substance A) and 15-30 min (glucose) of the measured concentration-time profile
      was developed. The mean residence time, the rate constants of absorption and
      elimination parameters of our model were calculated. Comparing to the Bateman
      function, our results demonstrate better approximation of the substance A and
      glucose concentration-time profile and estimation of absorption rate constant by
      our structural model. Obtained model results indicate that the atypical shape of
      measured concentration-time profile of single dose oral administration of drug
      was probably caused by the gastrointestinal and circulation system with deep
      compartment. This applies to the substances with high coefficient of absorption. 

PMID- 24019566
TI  - Fabrication and Evaluation of Curcumin-loaded Nanoparticles Based on Solid Lipid
      as a New Type of Colloidal Drug Delivery System.
AB  - Curcumin has very broad spectrum of biological activities; however,
      photodegradation, short half-life and low bioavailability have limited its
      clinical application. Curcumin-loaded solid lipid nanoparticles were studied to
      overcome these problems. The aim of this study was to optimize the best
      formulation on curcumin-loaded solid lipid nanoparticles. Emulsion-evaporation
      and low temperature-solidification technique was applied with monostearin as
      lipid carriers. The single factor analysis and orthogonal design were used to
      optimize formulation and various parameters were investigate. By the optimisation
      of a single factor analysis and orthogonal test, the particles size,
      polydispersity index, zeta potential, encapsulation efficiency and drug loading
      capacity of the optimised formulation were 99.99 nm, 0.158, -19.9 mV, 97.86%, and
      4.35%, respectively. The differential scanning calorimetry and X-ray diffraction
      analysis results demonstrated new structure was formed in nanoparticles. The
      release kinetics in vitro demonstrated curcumin-loaded solid lipid nanoparticles
      can control drug release. These studies confirmed that curcumin-loaded solid
      lipid nanoparticles could be prepared successfully with high drug entrapment
      efficiency and loading capacity. Curcumin-loaded solid lipid nanoparticles may be
      a promising drug delivery system to control drug release and improve
      bioavailability. 

PMID- 24019567
TI  - Design and development of polyethylene oxide based matrix tablets for verapamil
      hydrochloride.
AB  - In the present investigation an attempt has been made to increase therapeutic
      efficacy, reduced frequency of administration and improved patient compliance by
      developing controlled release matrix tablets of verapamil hydrochloride.
      Verapamil hydrochloride was formulated as oral controlled release matrix tablets
      by using the polyethylene oxides (Polyox WSR 303). The aim of this study was to
      investigate the influence of polymer level and type of fillers namely lactose
      (soluble filler), swellable filler (starch 1500), microcrystalline cellulose and
      dibasic calcium phosphate (insoluble fillers) on the release rate and mechanism
      of release for verapamil hydrochloride from matrix tablets prepared by direct
      compression process. Higher polymeric content in the matrix decreased the release
      rate of drug. On the other hand, replacement of lactose with anhydrous dibasic
      calcium phosphate and microcrystalline cellulose has significantly retarded the
      release rate of verapamil hydrochloride. Biopharmaceutical evaluation of
      satisfactory formulations were also carried out on New Zealand rabbits and
      parameters such as maximum plasma concentration, time to reach peak plasma
      concentration, area under the plasma concentration time curve(0-t) and area under
      first moment curve(0-t) were determined. In vivo pharmacokinetic study proves
      that the verapamil hydrochloride from matrix tablets showed prolonged release and
      were be able to sustain the therapeutic effect up to 24 h. 

PMID- 24019568
TI  - Effect of Zidovudine and its interaction with rocuronium on neuromuscular
      transmission.
AB  - Neuromuscular weakness is often found in patients receiving zidovudine therapy
      due to mitochondrial damage. Effect of zidovudine was evaluated in indirectly and
      directly stimulated isolated rat phrenic nerve hemidiaphragm preparations, by
      cumulative dose response curve with square wave pulses, 0.5 ms duration of 2 Hz
      at every 10 s. To understand the observed effect of zidovudine, interaction
      studies were carried out with rocuronium. Dose response curve of rocuronium was
      compared in the absence and in the presence of 1.2 and 12 mmol/ml zidovudine. In
      another set of experiment, intact animals were treated with zidovudine 50 and 100
      mg/kg for 15 days and phrenic nerve hemidiaphragm was obtained for in vitro
      experiment. Effect of zidovudine (30 mmol/ml) on twitch responses inhibited by
      dantrolene 50 MUmol/ml, magnesium chloride 8 mmol/ml, rocuronium 10 MUmol/ml,
      succinylcholine 25 MUmol/ml and lignocaine 600 MUmol/ml was studied. Zidovudine
      (3-30 mmol/ml) significantly augmented the twitch responses up to 80 and 40% in
      indirectly and directly stimulated preparations, respectively (P<0.05).
      Zidovudine did not show significant interaction with rocuronium in any group as
      per dose response curve and inhibitory concentration 5%, inhibitory concentration
      50% and inhibitory concentration 95% of rocuronium. Zidovudine (30 mmol/ml)
      augmented the twitch responses inhibited by dantrolene, magnesium chloride and
      rocuronium. It reduced the time for complete block of succinylcholine (P<0.05).
      Zidovudine affects the neuromuscular transmission. No conclusive interaction
      between rocuronium and zidovudine was found. 

PMID- 24019569
TI  - Validated Stability-indicating Reverse-phase Ultra-performance Liquid
      Chromatography Method for Simultaneous Determination of Sodium Methylparaben,
      Sodium Propylparaben and Ketorolac Tromethamine in Topical Dosage Forms.
AB  - A sensitive, fast, and stability-indicating isocratic reverse-phase ultra
      performance liquid chromatography method was developed and validated for
      quantitative simultaneous determination of sodium methylparaben, sodium
      propylparaben and ketorolac tromethamine in topical dosage forms. Separation of
      all peaks was achieved by using acquity ethylene bridged hybrid C18 (50*2.1 mm,
      1.7 MU) as stationary phase, mobile phase used was triethylamine buffer (pH
      2.5):tetrahydrofuran:methanol (665:35:300, v/v/v) with isocratic mode at a flow
      rate of 0.40 ml/min. All component were detected at 252 nm with 10 min run time.
      The described method was found to be linear in the concentration range of 248-744
      MUg/ml for ketorolac tromethamine, 20.8-62.4 MUg/ml for sodium methylparaben and
      2.38-7.13 MUg/ml for sodium propylparaben with correlation coefficients more than
      0.999. Method was validated in terms of specificity, linearity, accuracy,
      precision, solution stability, filter equivalency, and robustness as per
      International Conference on Harmonization guideline. Formulation was exposed to
      the stress conditions of peroxide, acid, base, thermal, and photolytic
      degradation and proven all components were well separated in the presence of
      degradants. 

PMID- 24019570
TI  - Investigation of release pattern of a drug with low solubility through asymmetric
      membrane capsules.
AB  - Asymmetric membrane capsules are a type of osmotic drug delivery systems. They
      are nondisintegrating capsules, which utilize osmotic pressure to drive the drug
      outwards for controlled delivery. Preceded by systems such as elementary osmotic
      pump, controlled porosity osmotic pump, single composition osmotic tablet this
      system has the advantage of simple and easy fabrication as it obviates the
      necessity of drilling an orifice into the drug delivery system. Moreover; it
      seems to be a low-cost alternative. The cellulose acetate capsule shell, on
      coming in contact with the aqueous medium shows in situ pore formation due to
      leaching of pore formers, which have been incorporated into the shell forming
      solution. Until date, a number of osmotic agents to the likes of sodium chloride,
      mannitol has been used to build up osmotic pressure inside the cell. The system
      is endowed with high water flux, which is a plus point for delivery of poorly
      soluble drugs like cephalexin in terms of increasing release rates. Studies
      envisaged in this research include the effect of different concentrations of
      different pore formers on in vitro drug release as well as the effect of
      modification of inner contents of the capsule. The system was successful in
      producing a gradual release of drug for 12 h. 

PMID- 24019571
TI  - Nondestructive and rapid concurrent estimation of paracetamol and nimesulide in
      their combined dosage form using Raman spectroscopic technique.
AB  - A rapid, nondestructive Raman spectroscopic method was developed for quantitative
      estimation of paracetamol and nimesulide in their combined dosage form. A Raman
      univariate calibration model was developed by measuring the peak intensities of
      paracetamol and nimesulide at 853 cm(-1) and 1336 cm(-1), respectively. The
      developed method was successfully applied for in situ, concurrent estimation of
      paracetamol and nimesulide in their combined dosage and method was also validated
      according to International Conference on Harmonisation guidelines. Thus, the
      developed Raman spectroscopic method can be applied for simultaneous estimation
      of paracetamol and nimesulide in their combined dosage form as a process
      analytical technology tool by pharmaceutical industries for routine quality
      control. 

PMID- 24019572
TI  - Antidiabetic and antihyperlipidemic effects of Thespesia populnea fruit pulp
      extracts on alloxan-induced diabetic rats.
AB  - Present study was carried to find out the antihyperglycemic and
      antihyperlipidemic activity of ethanol and aqueous extract of Thespesia populnea
      fruit pulp on alloxan-induced diabetic rats. Diabetes was induced in rats by
      administration of alloxan (150 mg/kg, i.p.). After the successful induction of
      experimental diabetes, the rats were divided into five groups each comprising a
      minimum of six rats. Phytochemical analysis and acute toxicity study of extracts
      was also done. The effects of extracts and metformin on fasting blood glucose and
      plasma lipid were examined for 28 days. Statistical analysis was carried out by
      using analysis of variance followed by Dunnet's multiple comparison test and
      paired t-test were done as the test of significance using GraphPad Prism. P<=0.05
      was considered as the minimal level of statistical significance. Therapeutic dose
      of extract was found to be 200 mg/kg on the basis of acute toxicity study.
      Aqueous and alcoholic extract showed a significant reduction in blood glucose
      levels as well as a lipid profile of diabetic rats at the end of 28(th) day of
      treatment. However, in groups treated with plant extract the reduction in the
      blood glucose and improvement in lipid profile was slightly less than that
      achieved with the standard group (metformin). From this study, it can be
      concluded that ethanol and aqueous extract of Thespesia populnea exhibited
      significant antihyperglycemic and antihyperlipidemic effects on alloxan-induced
      diabetic rats. 

PMID- 24019573
TI  - Development and Validation of a Reversed-Phase High-performance Liquid
      Chromatography Method for Determination of Desmopressin in Chitosan
      Nanoparticles.
AB  - A simple isocratic reversed-phase high performance liquid chromatographic method
      was developed for determination of released desmopressin from chitosan
      nanoparticles in the in vitro media. The chromatographic separation was achieved
      with acetonitrile/water (25:75, v/v), in which water contained 0.1% v/v
      trifluoroacetic acid with pH=2.5 as mobile phase, a Chromolith((r)) Performance
      RP-18e column (150*4.6 mm; 5 MUm) kept at 40 degrees  and ultraviolet detection
      at 220 nm. The compound was eluted isocritically at a constant flow rate of 1.6
      ml/min. The method was validated according to the International Conference on
      Harmonisation guidelines. The validation characteristics included accuracy,
      precision, linearity rang, selectivity, limit of detection, limit of quantitation
      and robustness. The calibration curve was linear (r>0.9999) over the
      concentration rang 0.5-100 MUg/ml. The limit of detection and limit of
      quantitation in the release media were 0.05 and 0.5 MUg/ml, respectively. The
      proposed method had an accuracy of and intra- and inter-day precision <4.2.
      Furthermore, to evaluate the performance of the proposed method, it was used in
      the analysis of desmopressin level in real samples containing chitosan
      nanoparticles in the in vitro media. 

PMID- 24019574
TI  - Formulation and Evaluation of Alstonia boonei Stem Bark Powder Tablets.
AB  - The aim of this work was to formulate Alstonia boonei dried stem bark powder into
      tablets by wet granulation method using acacia, gelatine and sodium carboxymethyl
      cellulose as binders at concentrations of 1, 2, 4 and 8% w/w. The phytochemistry
      of the stem bark of Alstonia boonei was evaluated. The micromeritic properties of
      the granules prepared were studied. The tablets were evaluated using the
      necessary official and unofficial tests. The results of the phytochemical
      analysis showed that alkaloids, tannins, steroids, saponins, glycosides,
      flavonoids and terpenoids were present while anthroquinones and acidcompounds
      were absent. Micromeritic studies showed that Alstonia boonei granules had good
      flowability. The formulated tablets complied with British Pharmacopoeial
      specification for weight uniformity, hardness (>=5 kgf) and tablet friability
      (<1%). For disintegration test, tablets formulated with gelatine and acacia at
      concentrations of 1, 2 and 4% w/w complied with Pharmacopoeial specification.
      However, tablets formulated with SCMC (1-8% w/w) and 8% w/w of acacia and
      gelatine failed the disintegration tests (Disintegration time more than 15 min). 

PMID- 24019575
TI  - Rapid Estimation of Tadalafil by Reverse-phase High-performance Liquid
      Chromatography Method in Bulk and Tablet Formulation.
AB  - The simple, selective, precise and accurate reverse-phase high-performance liquid
      chromatography method was developed and validated for analysis of tadalafil in
      bulk and tablet dosage form. The column was Inertsil C18 (150*4.6 mm; 5 MUm) in
      isocratic mode. The mobile phase used was phosphate buffer (10 mM, pH 3.2) and
      acetonitrile (50:50% v/v) at the flow rate of 1.0 ml/min with ultraviolet
      detection at 295 nm at ambient temperature. The retention time for tadalafil was
      found to be 4.01 min. Linearity was observed in the concentration range from 60
      to 140 MUg/ml for tadalafil with a correlation coefficient of (r (2)) 0.9998. The
      method was validated according to International Conference on Harmonisation
      guidelines in terms of linearity, accuracy, precision and specificity. Hence, the
      proposed method can be utilized for routine quality control of tadalafil in bulk
      and tablet dosage form. 

PMID- 24019576
TI  - Synthesis, characterisation and antitumour activity of some quercetin analogues.
AB  - Quercetin is one of the most abundant naturally occurring flavonoid and is
      associated with a wide range of biological activities, such as antioxidant,
      antiinflammatory and anticancer activities. However, there are multiple problems
      associated with the bioavailability of quercetin, thereby restricting its use.
      Taking this into consideration, the structure of quercetin was modified by
      removal of multiple hydroxyl groups and introduction of substituents such as Cl,
      OCH3 and N (CH3)2 on the p-position of the B-ring. The effect of structural
      modification on the anticancer activity was studied using four different cell
      lines, including MCF-7, HepG2, HCT-15 and PC-3. Compound 1a has shown an activity
      better than quercetin in HepG2 cell lines, whereas 1c and 1e showed significant
      growth inhibition of the HCT-15 cell lines. 

PMID- 24019577
TI  - Development and Validation of Reverse-phase High-performance Liquid
      Chromatography Method for Estimation of Citicoline Sodium in Bulk and Dosage
      Form.
AB  - A simple, accurate, precise and sensitive reverse-phase high-performance liquid
      chromatography method for the determination of citicoline sodium has been
      developed and validated. Drug was resolved on a C18 column (Phenomenex Luna,
      250*4.6 mm, 10MU), utilizing mobile phase of potassium dihydrogen phosphate
      buffer and acetonitrile in a ratio of 30:70. Mobile phase was delivered at the
      flow rate of 1.0 ml/min and detection was carried out at 272 nm. Separation was
      completed within 2.22 min. Calibration curve was linear with good correlation
      coefficient (R(2)=0.999) over a concentration range 10-60 MUg/ml. Recovery was
      between 98.84 and 101.76%. Method was found to be reproducible with relative
      standard deviation for intra and interday precision of <2.0% over the said
      concentration range. The method was successfully applied to the determination of
      the citicoline sodium, it can be very useful and an alternate to performing the
      stability studies. 

PMID- 24019578
TI  - Cymbopogon citratus Protects against the Renal Injury Induced by Toxic Doses of
      Aminoglycosides in Rabbits.
AB  - Renal injury is the most common side-effect of aminoglycosides. These
      antimicrobial drugs are particularly effective against Gram-negative
      microorganisms. The present study was conducted to investigate the renal
      protective activity of Cymbopogon citratus in gentamicin-induced nephrotoxicity.
      Male rabbits were divided into four groups (n=6) including group 1 (0.9% saline
      treated), group 2 (80 mg/kg/day gentamicin-treated), group 3 (200 mg/kg/day
      Cymbopogon citratus treated) and group 4 (80 mg/kg/day gentamicin and 200
      mg/kg/day Cymbopogon citratus treated). Biochemical kidney functioning
      parameters, urinary enzymes and histopathological examination were performed. The
      results of the present study showed that simultaneous administration of
      Cymbopogon citrates and gentamicin significantly protected alteration in body
      weight, blood urea nitrogen, serum creatinine, creatinine clearance, serum uric
      acid, serum electrolytes, urinary volume, urinary protein, urinary lactate
      dehydrogenase and urinary alkaline phosphatase induced by gentamicin.
      Histological examination of the kidney also suggested the same. It is concluded
      from the current study that co-administration of Cymbopogon citratus with
      gentamicin for 3 weeks successfully prevented renal damage associated with
      aminoglycosides. 

PMID- 24019580
TI  - Origin of magmas in subduction zones: a review of experimental studies.
AB  - Studies of the origin of magmas in subduction zones, particularly in the Japanese
      island arc, have been significantly advanced by petrological, geochemical,
      geophysical and experimental studies during last 50 years. Kuno's original
      model(1)) for magma generation in the Japanese island arc, that tholeiite magmas
      are formed at relatively shallow levels in the mantle on the Pacific Ocean side
      whereas alkali basalt magmas are formed in deeper levels on the Japan Sea side,
      stimulated subsequent studies, particularly high-pressure experimental studies in
      which the author participated. Recent seismic tomographic studies of regions
      beneath the Japanese island arc demonstrate that seismic low-velocity zones where
      primary magmas are formed have finger-like shapes and rise obliquely from the
      Japan Sea side toward the Pacific Ocean side. Based on experimental studies, it
      is suggested that the compositions of primary magmas depend mainly on the H2O
      content and degree of melting in the melting zones, and that primary tholeiite
      magmas are formed by 10-25% melting of the source mantle containing less than 0.2
      wt.% H2O. High-alumina basalt and alkali basalt magmas are formed by smaller
      degrees of melting of similar mantle, whereas primary boninite magmas are formed
      by more than 20% melting of the source mantle with more than 0.2 wt.% H2O, and
      finally, high-magnesia andesite magmas are formed by smaller degrees of melting
      of similar mantle. 

PMID- 24019579
TI  - Stress degradation studies on embelin.
AB  - Embelin, a naturally occurring benzoquinone, is obtained from fruits of Embelia
      ribes, which plays a vital role in the Ayurvedic system of medicine. The
      benzoquinone has diverse pharmacological and therapeutic properties and now
      constitutes a part of modern medicine. The aim of our study was to observe the
      effect of various stress conditions on this potential drug candidate. Embelin was
      subjected to stress conditions of acid and alkaline hydrolysis, oxidation,
      photolysis and thermal degradation. A significant degradation was found to occur
      by acid hydrolysis, oxidation and to a lesser extent under thermal stress and
      alkaline hydrolysis; the compound was found to be stable to photolytic stress.
      Further, the degradation product resulting from the acid hydrolysis was isolated
      and its structure was elucidated using spectroscopic techniques. Stress
      degradation studies on embelin provide an insight for its stability and storage
      considering the formulation aspects of modern medicine. 

PMID- 24019582
TI  - Antineutrino science by KamLAND.
AB  - KamLAND measured the nu e's flux from distant nuclear reactors, and found fewer
      events than expected from standard assumptions about nu e propagation at the
      99.998% confidence level (C.L.). The observed energy spectrum disagrees with the
      expected spectral shape at 99.6% C.L., and prefers the distortion from neutrino
      oscillation effects. A two-flavor oscillation analysis of the data from KamLAND
      and solar neutrino experiments with CPT invariance, yields [Formula: see text]
      eV(2) and [Formula: see text]. All solutions to the solar neutrino problem except
      for the large mixing angle (LMA) region are excluded. KamLAND succeeded in
      detecting geoneutrinos produced by the decays of (238)U and (232)Th within the
      Earth. The total observed number of 4.5 to 54.2, assuming a Th/U mass
      concentration ratio of 3.9 is consistent with 19 predicted by geophysical models.
      This detection allows better estimation of the abundances and distributions of
      radioactive elements in the Earth, and of the Earth's overall heat budget. 

PMID- 24019581
TI  - Mammalian Nemo-like kinase enhances beta-catenin-TCF transcription activity in
      human osteosarcoma and neuroblastoma cells.
AB  - Nemo-like kinase (NLK) is an evolutionarily conserved serine/threonine kinase and
      has been considered to be a suppressor of Wnt signaling in mammalian cells. Our
      study, however, has raised the possibility that NLK also functions as a Wnt
      signaling activator. In human osteosarcoma and neuroblastoma cell lines, NLK
      specifically enhanced beta-catenin-TCF complex transcription activity. The effect
      required kinase activity of NLK and co-expression of the beta-catenin DeltaN
      (constitutive active mutant of beta-catenin). The nuclear localization of
      Lymphoid enhancer factor 1 (LEF1) and beta-catenin DeltaN was not altered by NLK
      overexpression regardless of its effect on beta-catenin-TCF complex activity.
      Reporter analysis using LEF1 mutants at known NLK target sites indicated that NLK
      may have different activation targets for beta-catenin-TCF complex. Mutations in
      the potential NLK phosphorylation sites in beta-catenin did not change its
      transcription activity either. Our results suggest that NLK positively regulates
      Wnt/beta-catenin signaling in a cell type dependent manner through an
      unidentified mechanism. 

PMID- 24019583
TI  - The role of mammalian autophagy in protein metabolism.
AB  - Autophagy is in principle a non-selective degradation system within cells, which
      is conserved in all eukaryotic cells. Autophagy is usually suppressed at low
      levels but can be upregulated during periods of nutrient starvation, which
      facilitates cell survival. In addition to this fundamental role, basal autophagy
      was recently revealed to be important for constitutive turnover of intracellular
      proteins and organelles. Autophagy has been considered to be involved also in
      presentation of endogenous antigens, degradation of invasive bacteria, tumor
      suppression, cell death and development. This review will discuss the biological
      significance of autophagy, particularly focusing on its implications in protein
      metabolism in mammals. 

PMID- 24019585
TI  - Chemistry of a novel zerovalent ruthenium pi-acidic alkene complex, Ru (eta (6)
      1,3,5-cyclooctatriene)(eta (2)-dimethyl fumarate)2.
AB  - A novel zerovalent ruthenium complex with a pi-acidic ligand, Ru(eta (6)
      cyclooctatriene)(eta (2)-dimethyl fumarate)2 (1), was prepared from Ru(eta (4)
      cyclooctadiene)(eta (6)-cyclooctatriene) [Ru(cod)(cot)]. Complex 1 or
      Ru(cod)(cot) catalyzes various new carbon-carbon bond-forming reactions that
      include the [2 + 2] cycloaddition of alkenes and alkynes via ruthenacycles, the
      creation of a new hydrocarbon, pentacyclo[6.6.0.0(2,6).0(3,13).0(10,14)]tetradeca
      4,11-diene [PCTD], by dimerization of 2,5-norbornadiene via C-C bond cleavage,
      and the codimerization of alkynes and/or alkenes. Complex 1 was shown to be an
      excellent mother complex for various zerovalent ruthenium complexes. Complex 1
      reacts with amines, phosphines or water to give new zerovalent ruthenium
      complexes with the ligands. The resulting aqua complexes have a water ligand with
      an oxygen atom that is a chiral center, i.e., ruthenium complexes with a 'chiral
      water' ligand were prepared and fully characterized. 

PMID- 24019584
TI  - Contributions to the field of neurotransmitters by Japanese scientists, and
      reflections on my own research.
AB  - PART I DESCRIBES IMPORTANT CONTRIBUTIONS MADE BY SOME JAPANESE PIONEERS IN THE
      FIELD OF NEUROTRANSMITTERS: (their achievements in parentheses) J. Takamine
      (isolation and crystallization of adrenaline); K. Shimidzu (early hint for
      acetylcholine as a neurotransmitter); F. Kanematsu (donation of the Kanematsu
      Memorial Institute in Sydney); T. Hayashi (discovery of the excitatory action of
      glutamate and the inhibitory action of GABA); and I. Sano (discovery of a high
      concentration of dopamine in striatum, its reduction in a patient with
      Parkinson's disease and the treatment with DOPA). In Part II, I present some of
      my reflections on my research on neurotransmitters. The work of my colleagues and
      myself has made some significant contributions to the establishment of
      neurotransmitter roles played by GABA and substance P, the first amino acid and
      the first peptide neurotransmitters, respectively. By the early 1960s, 3
      substances, i.e., acetylcholine, noradrenaline, and adrenaline, had been
      established as neurotransmitters. Now the number of neurotransmitters is believed
      to be as many as 50 or even more mainly due to the inclusion of several amino
      acids and a large number of peptide transmitters. 

PMID- 24019587
TI  - The effect of iron spin transition on electrical conductivity of (Mg,Fe)O
      magnesiowustite.
AB  - We measured the electrical conductivity of Mg0.81Fe0.19O magnesiowustite, one of
      the important minerals comprising Earth's lower mantle, at high pressures up to
      135 GPa and 300 K in a diamond-anvil cell (DAC). The results demonstrate that the
      electrical conductivity increases with increasing pressure to about 60 GPa and
      exhibits anomalous behavior at higher pressures; it conversely decreases to
      around 80 GPa and again increases very mildly with pressure. These observed
      changes may be explained by the high-spin to low-spin transition of iron in
      magnesiowustite that was previously reported to occur in a similar pressure
      range. A very small pressure effect on the electrical conductivity above 80 GPa
      suggests that a dominant conduction mechanism changes by this electronic spin
      transition. The electrical conductivity below 2000-km depth in the mantle may be
      much smaller than previously thought, since the spin transition takes place also
      in (Mg,Fe)SiO3 perovskite. 

PMID- 24019586
TI  - Novel function of lipids as a pheromone from the Harderian gland of golden
      hamster.
AB  - Sexual diversity of ADG in Harderian gland of golden hamster was demonstrated on
      TLC. Female ADG contained iso- and anteiso-branched acyl and alkyl components,
      but male ADG contained only straight chain ones, which suggested the hormonal
      control of the expression of acyl-CoA dehydrogenases in the catabolism of BCAA.
      Acyl-CoA dehydrogenases were not expressed in the absence of testosterone, and
      then isovaleryl-CoA, 2-methylbutyryl-CoA, and isobutyryl-CoA accumulated, and
      acted as primers for the synthesis of iso- and anteiso-branched fatty acids. The
      incorporation of [U-(14)C] leucine into lipids was monitored by TLC. The
      cholesterol fraction was labeled in males but not in female, which means that
      cholesterol was not produced from BCAA in female gland due to the lack of
      expression of acyl-CoA dehydrogenases. We monitored the behavior of male hamsters
      toward female gland lipids, and found slightly greater attractiveness in female
      ones than that in male ones although the difference was not significant.
      Considering the lifestyle of golden hamster in nature, we propose a hypothesis
      that the lipids from the Harderian gland of golden hamster serve as a pheromone
      to declare their territory and to seek the mate with good congeniality. 

PMID- 24019588
TI  - Phenotypic reversion in analbuminemic rats due to an altered splicing mechanism.
AB  - Serum albumin is regarded as an important and indispensable protein, but
      analbuminemic rats established by Sumi Nagase in 1977 seems to exhibit few
      symptoms in spite of an almost total lack of albumin in the serum. The albumin
      gene of analbuminemic rats was found to have a seven-base-pair deletion in an
      intron, close to exon-intron junction, resulting in the formation of non
      functional mRNA in hepatocytes. Immunostaining for albumin was negative in young
      analbuminemic rat hepatocytes, but a significant number of immunoreactive
      hepatocytes were observed in aged rats. The incidence of immunoreactive
      hepatocytes increased with aging. Surprisingly, many immunoreactive hepatocytes
      were observed after hepatocarcinogen treatment sometimes in large clusters.
      Albumin transcripts in analbuminemic rat liver after treatment with carcinogen,
      showed an altered pattern of exon-skipping. The altered albumin molecules thus
      synthesized accumulated in cellular organelles. Analbuminemic rats exhibited a
      high sensitivity in various organs to different types of carcinogens. Further
      challenges remain regarding the biology of analbuminemic rats. 

PMID- 24019589
TI  - Biochemical principle of Limulus test for detecting bacterial endotoxins.
AB  - A hemocyte lysate from horseshoe crab (Limulus) produced a gel, when exposed to
      Gram-negative bacterial endotoxins, lipopolysaccharides (LPS). This gelation
      reaction of the lysate, so-called Limulus test, has been widely employed as a
      simple and very sensitive assay method for endotoxins. Recent biochemical studies
      on the principle of Limulus test indicate that the hemocytes contain several
      serine protease zymogens, which constitute a coagulation cascade triggered by
      endotoxins, and that there is a (1,3)-beta-D-glucan-mediated coagulation pathway
      which also results in the formation of gel. Up to now, six protein components,
      designated coagulogen, proclotting enzyme, factor B, factor C, and factor G, all
      of which are closely associated with the endotoxin-mediated coagulation pathway,
      have been purified and biochemically characterized. The molecular structures of
      these proteins have also been elucidated. Moreover, the reconstitution
      experiments using the isolated clotting factors, factor C, factor B, proclotting
      enzyme and coagulogen in the presence of endotoxin, leads to the formation of
      coagulin gel. Here, I will focus on the biochemical principle of Limulus test for
      detecting bacterial endotoxins, and its activation and regulation mechanism on
      the LPS-mediated coagulation cascade. 

PMID- 24019590
TI  - Hemoglobin magnetism in aqueous solution probed by muon spin relaxation and
      future applications to brain research.
AB  - A marked difference in spin relaxation behavior due to hemoglobin magnetism was
      found for positive muons (MU(+)) in deoxyhemoglobin in comparison with that
      observed in oxyhemoglobin in aqueous solution at room temperature under zero and
      external longitudinal magnetic fields upto 0.4 Tesla. At the same time, small but
      significant unique relaxation pattern was observed in nonmagnetic oxyhemoglobin.
      Combined with our previous measurements on hemoglobin in human blood, application
      of this type of measurement to the studies of the level of oxygenation in various
      regions of the human brain is suggested. 

PMID- 24019591
TI  - Development of highly potent chiral discrimination methods that solve the
      problems of the diastereomer method.
AB  - The development of highly potent chiral discrimination methods that solve the
      problems of the diastereomer method, in which it is impossible to discriminate
      the diastereomers having chiral centers separated by more than four bonds, is
      described. On the basis of the results obtained, a new hypothesis, Induced Chiral
      Fields that the achiral reversed phase can provide chiral fields depending on the
      structures of the eluents, is proposed to explain the significant results of
      separation of the diastereomers derived from newly developed chiral and
      fluorescent labeling reagents and optical isomers by reversed-phase HPLC, which
      was hitherto impossible. 

PMID- 24019592
TI  - Interaction between the immune system and bone metabolism: an emerging field of
      osteoimmunology.
AB  - The interaction between the immune and bone systems has long been appreciated,
      but recent research into arthritis as well as various bone phenotypes found in
      immune-related knockout mice has highlighted the importance of the interplay and
      the interdisciplinary field called osteoimmunology. In rheumatoid arthritis, IL
      17-producing helper T cells (TH17) induces receptor activator of NF-kappaB ligand
      (RANKL), which stimulates osteoclast differentiation through nuclear factor of
      activated T cells (NFAT)c1. Accumulating evidence suggests that the immune and
      skeletal systems share cytokines, signaling molecules, transcription factors and
      membrane receptors. In addition, the immune cells are maintained in the bone
      marrow, which provides a space for mutual interaction. Thus, bone turns out to be
      a dynamic tissue that is constantly renewed, where the immune system participates
      to a hitherto unexpected extent. This emerging field of osteoimmunology will be
      of great importance not only to the better understanding of the two systems but
      also to the development of new treatment for rheumatic diseases. 

PMID- 24019593
TI  - Super strong nuclear force caused by migrating K mesons - Revival of the Heitler
      London-Heisenberg scheme in kaonic nuclear clusters.
AB  - We have studied the structure of K (-) pp comprehensively by solving this
      threebody system in a variational method, starting from the Ansatz that the
      Lambda(1405) resonance (=Lambda (*)) is a K (-) p bound state. The structure of K
      (-) pp reveals a molecular feature, namely, the K (-) in Lambda (*) as an "atomic
      center" plays a key role in producing strong covalent bonding with the other
      proton. We point out that strongly bound K nuclear systems are formed by "super
      strong" nuclear force due to migrating real bosonic particles K a la Heitler
      London-Heisenberg, whereas the normal nuclear force is caused by mediating
      virtual mesons. We have shown that the elementary process, p + p -> K (+) +
      Lambda (*) + p, which occurs in a short impact parameter and with a large
      momentum transfer, leads to unusually large self-trapping of Lambda (*) by the
      involved proton, since the Lambda (*)-p system exists as a compact doorway state
      propagating to K (-) pp. 

PMID- 24019594
TI  - Amino, Ammonio and Aminioethenes: A Theoretical Study of their Structure and
      Energetics.
AB  - We have performed high level ab initio quantum mechanical calculations for
      aminoethene and the three isomeric 1,1- (Z)- or (E)-1,2-diaminoethenes as well as
      their singly and doubly charged cations derived by loss of electrons and/or upon
      protonation. Gas phase molecular structures were computed at the MP2/6
      311+G(3df,2p) level. Standard molar enthalpies of formation in the gas phase, at
      T = 298.15 K were estimated using the G3 composite method and atomization,
      isodesmic and homodesmotic reactions. Other energetic parameters were also
      calculated at the G3 level: proton affinities, basicities and adiabatic
      ionization enthalpies. Theoretical and experimental data are compared. The
      reported experimental data refer only to aminoethene wherein the standard molar
      enthalpy of formation has a considerable uncertainty, although the molecular
      structure is well-established. There are no such data, neither structural nor
      thermochemical, for any of the three isomeric diaminoethenes. Isoelectronic
      comparisons are made. For example, the diprotonated diaminoethenes are
      isoelectronic to isobutene and (Z)- and (E)-butene, while the doubly ionized
      diaminoethenes are likewise related to trimethylenemethane and 1,3-butadiene.

PMID- 24019595
TI  - Health in international development agenda: present, past and future.

PMID- 24019596
TI  - Mobile health clinics: meeting health needs of the urban underserved.

PMID- 24019597
TI  - Glaucoma: an emerging peril.

PMID- 24019598
TI  - Diabetes and hypertension in urban bhutanese men and women.
AB  - BACKGROUND: Bhutan is a mountainous country with 31% urban population. There is
      no information on prevalence of diabetes and hypertension in Bhutan yet. This was
      the first study of its kind conducted in the capital city. OBJECTIVE: To
      determine prevalence of diabetes, impaired fasting glucose (IFG), impaired
      glucose tolerance (IGT) and hypertension in urban Bhutanese population aged 25 to
      74 years. MATERIALS AND METHODS: Stratified two-stage sampling was adopted to
      include 2474 respondents (Males: 1132, Females: 1342) equally distributed among
      different age and sex groups. A questionnaire containing demographic, educational
      and social details and history of diabetes and hypertension was administered on
      the sampled population the previous evening and blood pressure measured the next
      morning in nearby camp where fasting blood samples were collected and an oral
      glucose tolerance test done. RESULTS: Age and sex standardized prevalence of
      diabetes, IGT and IFG were 8.2.0, 21.6 and 4%, respectively. Only 66.5% of the
      population had normal blood sugar. Prevalence of diabetes and IGT increased
      progressively with increasing age. Prevalence of hypertension was 26% (Males:
      28.3%, Females: 23.2%). It was observed that 54.1% of diabetes population had
      hypertension. CONCLUSION: The study shows that not only is prevalence of diabetes
      and hypertension high in the urban Bhutanese but also there is a high diagnosis
      and treatment gap in these disorders.

PMID- 24019599
TI  - Pattern, awareness and perceptions of health hazards associated with self
      medication among adult residents of kano metropolis, northwestern Nigeria.
AB  - BACKGROUND: Kano State is the most populous state, and one of those states
      pronounced with the highest prevalence of drug abuse in Nigeria. However, there
      is lack of documented data to back the assertion. OBJECTIVE: We determined the
      pattern, awareness and perceptions of the adult residents of Kano metropolis
      about self medication. MATERIALS AND METHODS: We used a descriptive cross
      sectional design to study a random sample of 380 adult in Kano metropolis. Data
      was collected using semi-structured questionnaires that were pretested outside
      the study area. Data analysis was with Epi Info(r) 3.5.1. RESULTS: The mean age
      of the subjects was 35.43 +/- 15.10 years, majority were males (66.32%), singles
      (47.11%) and had at least secondary education (67.63%). About three-quarter
      (78.95%) admitted using drug (s) in the past without prescription. Drugs commonly
      consumed were antimalarials (42.10%), analgesics (40.56%), antibiotics (29.41%),
      and cough mixtures (13.31%). Common sources of drugs were patent medicine stores
      (62.54%) and the market (19.81%). Common reasons for self medication were long
      queues in the hospitals (38.39%), and in-accessibility to doctors (25.08%). About
      two-thirds (65.00%) correctly perceived that self medication could be hazardous;
      and half (51.58%) were aware of at least one hazard of self medication.
      CONCLUSION/RECOMMENDATIONS: Irrational drug use is a growing challenge to public
      health in Kano, Nigeria. Thus, drug regulatory agencies in Nigeria should work
      together to ensure that all drug retail outlets and drug sellers are registered,
      controlled drugs are dispensed only on prescription of the physicians; and the
      laws safeguarding drug use are duly enforced. Health authorities should also
      strengthen efforts towards health educating the public.

PMID- 24019600
TI  - Infant Deaths - Data Disparity and Use of Ante, Intra and Post-natal Services
      Utilization: An Experience from Tribal Areas of Gujarat.
AB  - BACKGROUND: Infant death depends upon the care during the infancy and also upon
      the service utilization during antenatal and intra-natal periods and with its
      decline, it is necessary to find the under-reporting if any and identify the most
      appropriate agency for its reporting. OBJECTIVES: (1) To document disparities
      between different reporting systems about infant deaths and find out the under
      reporting if any and identify the most appropriate agency and (2) To identify
      utilization of health services during ante, intra and post-natal period for all
      infant deaths. MATERIALS AND METHODS: Study was conducted in 51 villages of 3
      Primary Health Centers (PHCs) from a tribal dominated Taluka (block) of South
      Gujarat during September - November 2005. Information was gathered for 1 year (1
      September 2004 to 31 August 2005) from 4 sources namely health care system,
      Integrated Child development services (ICDS) scheme, Civil Registration System
      (CRS) and Investigator himself (Gold standard). Data was collected in a designed
      verbal autopsy questionnaire by house to house survey and analyzed in Epi Info.
      RESULTS: A total of 48 infant deaths were recorded by investigator against
      reported 2, 10 and 8 infant deaths by CRS, Health System and ICDS respectively.
      While profiling these 48 infant deaths it was found that only 29.2% mothers
      received full antenatal care (ANC) and 60.4% delivered at home (by untrained
      personnel). Not a single delivery was done at PHCs or its sub centers (SC). In
      25% cases there was poor cord care. 39.6% mothers did not breastfeed and 35.4%
      gave pre-lacteal feeding. CONCLUSIONS: There was gross underreporting of infant
      mortality in all 3 agencies. The utilization of ANC and post natal care (PNC)
      services was poor in these death cases. Health system and ICDS need to be
      sensitized to work in coordination to provide quality ANC, INC and PNC to prevent
      such avoidable infant deaths.

PMID- 24019601
TI  - Feasibility of use of color-coded rings by nurse midwives: an appropriate
      technology based on partographic principles.
AB  - OBJECTIVES: To study the feasibility of use of color-coded rings as a proxy for
      partograph for early identification of slow progress of labor. MATERIALS AND
      METHODS: Color-coded rings were devised as a tool using appropriate technology to
      translate the partographic principles into simpler, easy to understand
      methodology. The rings were in pairs of 4 colors i.e., red, blue, yellow, and
      green, ranging from 3 cm to 10 cm in diameter with a difference of 4 cm between
      rings of the same color. The midwife performed p/v examination of the woman in
      labor to assess the initial cervical dilatation and identify corresponding ring.
      P/V was to be repeated after 4 hours to reassess the cervical dilatation and
      compare it with the bigger ring of the same color indicating expected cervical
      dilatation. If existing cervical dilatation measured lesser, it was interpreted
      as slow progress of labor indicating referral. RESULTS: 44 women [23 (22.1%)
      primis and 21 (13%) multis] showed delayed progress of labor as judged by use of
      color-coded rings. 20 women (4 primis and 16 multis) showed satisfactory progress
      or delivered by the time arrangements for referral were made. CONCLUSION: Use of
      color-coded rings may serve as a valuable tool based on appropriate technology to
      assess slow progress of labor not only in the hands of nurse midwives but it also
      can serve as a training tool for TBAs to help facilitate timely referral of such
      cases.

PMID- 24019602
TI  - Indoor air pollution from biomass combustion and its adverse health effects in
      central India: an exposure-response study.
AB  - BACKGROUND: Some of the highest exposures to air pollutants in developing
      countries occur inside homes where biofuels are used for daily cooking.
      Inhalation of these pollutants may cause deleterious effects on health.
      OBJECTIVES: To assess the respiratory and other morbidities associated with use
      of various types of cooking fuels in rural area of Nagpur and to study the
      relationship between the duration of exposure (exposure index [EI]) and various
      morbidities. MATERIALS AND METHODS: A total of 760 non-smoking, non-pregnant
      women aged 15 years and above (mean age 32.51 ? 14.90 years) exposed to domestic
      smoke from cooking fuels from an early age, working in poorly ventilated kitchen
      were selected and on examination presented with various health problems. Exposure
      was calculated as the average hours spent daily for cooking multiplied by the
      number of years. Symptoms were enquired by means of a standard questionnaire
      adopted from that of the British Medical Research Council. Lung function was
      assessed by the measurement of peak expiratory flow rate (PEFR). PEFR less than
      80% of the predicted was considered as abnormal pulmonary function. RESULTS AND
      CONCLUSIONS: Symptoms like eye irritation, headache, and diminution of vision
      were found to be significantly higher in biomass users (P < 0.05). Abnormal
      pulmonary function, chronic bronchitis, and cataract in biomass users was
      significantly higher than other fuel users (P < 0.05). Moreover an increasing
      trend in prevalence of symptoms/morbid conditions was observed with increase in
      EI. The presence of respiratory symptoms/morbid conditions was associated with
      lower values of both observed and percent predicted PEFR (P < 0.05 to 0.001).
      Thus women exposed to biofuels smoke suffer more from health problems and
      respiratory illnesses when compared with other fuel users.

PMID- 24019603
TI  - Factors associated with morbidities among infants in three sub centre areas of
      belgaum district of South India: a longitudinal study.
AB  - BACKGROUND: Health status of infants is a sensitive indicator of development and
      factors influencing it need to be better understood. OBJECTIVES: This study was
      conducted to search for factors associated with morbidity among infants and to
      find out their influence on weight gain during infancy. MATERIALS AND METHODS:
      This longitudinal study was undertaken in south India from November 2004 till
      April 2006. A birth cohort of all children born during first 6 months of the
      study period were assessed at enrollment and followed up monthly till they
      attained 1 year of age. RESULTS: Incidence of morbidity among infants was found
      to be least among those exclusively breast fed (EBF) for 6 months and most when
      EBF for less than 6 months (P = 0.045). It was also more when infants were weaned
      with a combination of animal milk, formula milk, semi-solids and solid diet and
      least when weaned only with semi-solids and solids (P = 0.018). Diarrheal
      episodes were more in infants who were bottle-fed (P < 0.001). Weight gain
      between 6(th) and 12(th) month of infancy was found to be significantly affected
      by various morbidities (P = 0.001). Incidence of morbidities was less among
      preterm babies and more among partially immunized (P < 0.001) babies with birth
      order >= 3 (P = 0.012), babies of mothers with low socio-economic and educational
      status. Delayed milestones during infancy was seen more in babies with history of
      birth asphyxia (P = 0.018). CONCLUSION: Several factors influenced incidence of
      morbidities and these morbidities had a negative effect on weight gain. Hence
      these factors need to be addressed to promote better child health.

PMID- 24019604
TI  - Association of obesity with hypertension amongst school-age children belonging to
      lower income group and middle income group in national capital territory of
      delhi.
AB  - BACKGROUND AND OBJECTIVES: Hypertension is one of the most common diseases world
      wide and the prevalence in school-aged children appears to be increasing perhaps
      as a result of increased prevalence of obesity. Thus, the present study was
      planned to establish an association between body mass index (BMI) and waist
      circumference (WC) with hypertension amongst school children in the age group of
      5-16 years belonging to lower income group (LIG) and middle income group (MIG) in
      National Capital Territory of Delhi. SUBJECTS AND METHODS: Population
      proportionate to size methodology was adopted to select 30 clusters/schools in
      each LIG and MIG category. About 170 children from each school were selected
      randomly with the help of random number tables. Anthropometric measurements of
      weight, height and WC and blood pressure measurements were taken by using the
      standard methodology. RESULTS AND INTERPRETATION: t0 he prevalence of high
      systolic blood pressure (SBP) in LIG and MIG school population was 3.8 and 4.4%
      with high WC and BMI are more likely to have hypertension. SUBJECTS AND METHODS:
      Population proportionate to size methodology was adopted to select 30
      clusters/schools in each LIG and MIG category. About 170 children from each
      school were selected randomly with the help of random number tables.
      Anthropometric measurements of weight, height and WC and blood pressure
      measurements were taken by using the standard methodology. RESULTS AND
      INTERPRETATION: t0 he prevalence of high systolic blood pressure (SBP) in LIG and
      MIG school population was 3.8 and 4.4% with high WC and BMI are more likely to
      have hypertension.

PMID- 24019605
TI  - Nutritional status of adolescents in agrarian crises-affected area of
      maharashtra.

PMID- 24019606
TI  - Judicious selection of m.d. Thesis topic: role of faculty in improving research
      in public health.

PMID- 24019607
TI  - Modified Kuppuswamy's Socioeconomic Scale: Social Researcher Should Include
      Updated Income Criteria, 2012.

PMID- 24019608
TI  - Adolescent health issues.

PMID- 24019609
TI  - Molecular aberration studies in cases of idiopathic mental retardation: An
      update.

PMID- 24019610
TI  - Birth defects in India: Hidden truth, need for urgent attention.
AB  - Birth defects (structural, functional and metabolic disorder present from birth,
      may be diagnosed later) rising up as an important cause of infant mortality even
      in developing countries where infant mortality has been reduced to much extent.
      Seventy percent of birth defects are preventable through the application of
      various cost effective community genetic services. Indian people are living in
      the midst of risk factors for birth defects, e.g., universality of marriage, high
      fertility, large number of unplanned pregnancies, poor coverage of antenatal
      care, poor maternal nutritional status, high consanguineous marriages rate, and
      high carrier rate for hemoglobinopathies. India being the second most populous
      country with a large number infant born annually with birth defects should focus
      its attention on strategies for control of birth defects. Many population based
      strategies such as iodization, double fortification of salt, flour fortification
      with multivitamins, folic acid supplementation, periconceptional care, carrier
      screening and prenatal screening are some of proven strategies for control of
      birth defects. Strategies such as iodization of salt in spite of being initiated
      for a long time in the past do have a very little impact on its consumption (only
      50% were using iodized salt). Community genetic services for control of birth
      defects can be easily flourished and integrated with primary health care in India
      because of its well established infrastructure and personnel in the field of
      maternal and child health care. As there is wide variation for infant mortality
      rate (IMR) in different states in India, so there is a need of deferential
      approach to implement community genetic services in states those had already
      achieved national goal of IMR. On the other hand, states those have not achieved
      the national goal on IMR priority should be given to management of other causes
      of infant mortality. 

PMID- 24019611
TI  - Children with isolated growth hormone deficiency: Empty sella versus normal
      sella.
AB  - BACKGROUND: Empty sella (ES) may be associated with variable clinical conditions
      ranging from the occasional discovery of a clinically asymptomatic pouch within
      the sella turcica to severe intracranial hypertension and rhinorrhea. The need
      for replacement hormone therapy in ES, as in other syndromes that may cause
      hypopituitarism, must be assessed for every single hormone, including growth
      hormone (GH). AIM: To determine whether or not the presence of ES could allow
      some changes in the GH responses of the isolated growth hormone deficiency (GHD)
      patients. MATERIALS AND METHODS: We included a cohort of 59 short stature
      children and adolescents with isolated GHD. According to computed tomography
      finding, they were classified into 2 groups: Group 1 included 40 children with
      normal sella and 19 children with ES in Group 2. All patients received
      recombinant human growth hormone (rhGH) with a standard dose of 20 IU/m(2)/week.
      RESULTS: The baseline results were not significantly different for all variables
      except weight standard deviation was smaller with statistical significant
      difference (P = 0.02). We identified no significant differences when comparing
      both groups, except for height standard deviation (HTSD) after the first year of
      therapy which revealed significant difference in favor of group 1. When comparing
      pre- and the two post-treatments HTSD results of the studied cases, all showed
      significant changes after GH therapy. The results of related variables pre-and
      post-treatment in both the groups showed significant improvement in all variables
      of the two groups of the study. CONCLUSION: Our study showed a similar stature
      outcome in the two treatment groups.

PMID- 24019612
TI  - Etiology and genetic factors in clefts of lip and/or palate reported at
      children's hospital, Lahore, Pakistan.
AB  - The etiology of cleft lip (CL) and/or cleft palate (CP) has been extensively
      studied in industrialized countries and is suggested to be heterogeneous with
      increasing evidence that both genetic and environmental factors are operating. To
      evaluate this assertion in a developing country like Pakistan, a case finding
      cross-sectional study was completed from 1(st) July 2010 to 31(st) May 2011 for
      100 cases of CL and/or CP referred to the Genetic Clinic of the Children's
      Hospital, Lahore, Pakistan. A clinical examination followed by necessary
      diagnostic work-up was completed for each case. The cause of CL and/or CP was
      clear in 18% of the children (n = 18). Environmental causes were found in 6
      children (four mothers developed hyperthermia during the 2(nd) month of
      gestation, one mother was diabetic, and one mother was a known case of epilepsy
      and took sodium valproate throughout her pregnancy). Six children were suffering
      from known genetic malformation syndromes (each with Jarcho-Levin syndrome, Oral
      Facial-Digital syndrome type XI, Oral-Duplication syndrome, Kabuki syndrome,
      Fronto-nasal dysplasia and Nager syndrome). Novel chromosomal aberrations were
      identified in 2 children. In 82% of the children (n = 82) the cause of oro-facial
      clefts remained unknown. Impact of gender and consanguinity on the development of
      CL and/or CP was also studied. Prevalence of CP was significantly more among
      female children as compared to that in males (P < 0.05). Associated anomalies
      were present in 18% of the cases, anomalies of the craniofacial region being the
      most common. These findings were compared with regional and international
      studies. 

PMID- 24019613
TI  - Analysis of cytotoxic T-lymphocyte-associated antigen-4 and MMP-9 genes'
      methylation and their expression profiles with risk of non-alcoholic fatty liver
      disease.
AB  - OBJECTIVE: To investigate the effect of promoter methylation of cytotoxic T
      lymphocyte-associated antigen-4 (CTLA-4) gene and matrix metalloproteinases
      (MMPs) on the risk of non-alcoholic fatty liver disease (NAFLD). MATERIALS AND
      METHODS: CTLA-4 and MMP-9 promoter methylation were investigated using a
      methylation-specific polymerase chain reaction (MS-PCR) in blood samples taken
      from 80 NAFLD individuals and 95 healthy controls. The expression levels of CTLA
      4 and MMP-9 were also assessed in 10 blood and 9 liver tissues mRNA samples from
      NAFLD patients. These cases were compared to the blood (n = 10) samples of
      healthy controls with real-time quantitative reverse transcriptase PCR. RESULTS:
      No significant relationship was found for methylation of CTLA-4 and MMP-9 between
      cases and controls. The relative expression of CTLA-4 and MMP-9 mRNA in NAFLD was
      not significantly different compared to healthy control samples. CONCLUSION: For
      the first time, our outcomes indicate that the methylation status of CTLA-4 and
      MMP-9 genes has no significant function on the process of NAFLD.

PMID- 24019614
TI  - Body composition in Egyptian Turner syndrome girls.
AB  - OBJECTIVE: This cross-sectional study was undertaken to construct the new body
      fat % curve and provide body composition reference data for adolescent girls with
      Turner syndrome (TS). They diagnosed cytogenetically by blood karyotyping and not
      treated with growth hormone (GH). MATERIALS AND METHODS: The study included 70 TS
      girls from age 13 years to age 17 years. Body composition was measured by
      bioelectrical impedance. Smoothed centile charts were derived by using the least
      mean square (LMS) method. RESULTS: The new body fat curves reflect the increase
      of body fat mass (FM) from age 13 years to age 17 years. Body FM % of Egyptian TS
      girls was lower when compared with age-matched American untreated TS girls.
      CONCLUSION: This study presents the new body fat curves and reference values of
      body composition for untreated Egyptian TS adolescent girls. The present charts
      can be used for direct assessment of body FM % for Egyptian TS girls and
      evaluation for cases on GH treatment or other growth promoting therapy.

PMID- 24019615
TI  - Haptoglobin2-2 phenotype is an additional risk factor of retinopathy in type 2
      diabetes mellitus.
AB  - AIMS: The aim of this study was to investigate the association between
      haptoglobin (Hp) phenotypes and risk of the development of diabetic retinopathy
      (DR) in patients of type 2 diabetes mellitus. MATERIALS AND METHODS: This cross
      sectional study included 45 normotensive type 2 diabetic patients (duration more
      than 5 years) admitted in the hospital divided into two groups (with and without
      DR) on the basis of fundus examination by direct ophthalmoscopy. Serum samples of
      all patients were subjected for Hp phenotyping by polyacrylamide gel
      electrophoresis. RESULTS: DR was associated significantly in diabetic patients
      with Hp2-2 phenotype (79.31%) than diabetic patients with Hp2-1 phenotype
      (43.75%) and Hp2-2 had higher odds ratio (OR) for DR in univariate analysis (OR
      4.929, [95% confidence interval [CI] (1.297-18.733)], P = 0.016) and multivariate
      analysis (OR 7.704 [95% CI (0.887-66.945)], P = 0.064). Furthermore, Hp2-2 was
      associated significantly with severe forms of DR. CONCLUSION: Hp2-2 phenotype is
      associated with susceptibility to DR showing a graded risk relationship to the
      number of Hp2 alleles. Determination of Hp phenotype may be useful in the risk
      assessment and management of DR.

PMID- 24019616
TI  - Measuring opportunity for natural selection: Adaptation among two linguistically
      cognate tribes inhabiting two eco-situations of North-East India.
AB  - BACKGROUND: Numerous literature on the migration of Mishings point out to the
      fact that the Mishing and the Minyong are two culturally and linguistically
      cognate tribes that co-existed in the same ecology in the hills of Arunachal
      Pradesh. The Mishing tribe after migration, now inhabits flood-prone areas of
      Brahmaputra valley of Assam. AIM: THE STUDY AIMS TO MEASURE THE ADAPTATION
      PROCESS OF THESE TWO COGNATE TRIBES INHABITING TWO DIFFERENT ECOLOGIES AT
      PRESENT: Hills and plains by calculating the index of selection intensity by
      Crow's and Johnston and Kensinger's formulae. MATERIALS AND METHODS: The
      reproductive histories of 77 Mishing mothers of completed fertility inhabiting a
      flood affected village of Assam and 74 Minyong mothers inhabiting a hilly village
      of Arunachal Pradesh are selected. RESULTS AND DISCUSSION: The Minyongs show
      higher average fertility than the Mishings. The proportion of embryonic death is
      higher, and child death is lower among the Mishings (0.1661; 0.1623) than the
      Minyongs (0.1319; 0.2238). The index of selection due to mortality component is
      contributing more toward the total index of selection in both the tribes.
      CONCLUSION: The contribution of mortality component is sizeable to the total
      selection like many other tribes of North-East India. Higher proportion of
      embryonic deaths among the Mishings infers that the causes are mostly biological
      whereas, the higher proportion of child deaths among the Minyongs infers that the
      causes are mostly socio-cultural.

PMID- 24019617
TI  - Multiplex ligation-dependant probe amplification study of children with
      idiopathic mental retardation in South India.
AB  - BACKGROUND: Mental retardation (MR) is a heterogeneous dysfunction of the central
      nervous system exhibiting complex phenotypes and has an estimated prevalence of 1
      3% in the general population. However, in about 50% of the children diagnosed
      with any form of intellectual disability or developmental delay the cause goes
      undetected contributing to idiopathic intellectual disability. MATERIALS AND
      METHODS: A total of 122 children with developmental delay/MR were studied to
      identify the microscopic and submicroscopic chromosome rearrangements by using
      the conventional cytogenetics and multiplex ligation dependent probe
      amplification (MLPA) analysis using SALSA MLPA kits from Microbiology Research
      Centre Holland [MRC] Holland. RESULTS: All the recruited children were selected
      for this study, after thorough clinical assessment and metaphases prepared were
      analyzed by using automated karyotyping system. None was found to have
      chromosomal abnormality; MLPA analysis was carried out in all subjects and
      identified in 11 (9%) patients. CONCLUSION: Karyotype analysis in combination
      with MLPA assays for submicroscopic micro-deletions may be recommended for
      children with idiopathic MR.

PMID- 24019618
TI  - Subtelomeric chromosomal rearrangements in a large cohort of unexplained
      intellectually disabled individuals in Indonesia: A clinical and molecular study.
AB  - CONTEXT: Unbalanced subtelomeric chromosomal rearrangements are often associated
      with intellectual disability (ID) and malformation syndromes. The prevalence of
      such rearrangements has been reported to be 5-9% in ID populations. AIMS: To
      study the prevalence of subtelomeric rearrangements in the Indonesian ID
      population. MATERIALS AND METHODS: We tested 436 subjects with unexplained ID
      using multiplex ligation dependent probe amplification (MLPA) using the specific
      designed sets of probes to detect human subtelomeric chromosomal imbalances
      (SALSA P070 and P036D). If necessary, abnormal findings were confirmed by other
      MLPA probe kits, fluorescent in situ hybridization or Single Nucleotide
      Polymorphism array. RESULTS: A subtelomeric aberration was identified in 3.7% of
      patients (16/436). Details on subtelomeric aberrations and confirmation analyses
      are discussed. CONCLUSION: This is the first study describing the presence of
      subtelomeric rearrangements in individuals with ID in Indonesia. Furthermore, it
      shows that also in Indonesia such abnormalities are a prime cause of ID and that
      in developing countries with limited diagnostic services such as Indonesia, it is
      important and feasible to uncover the genetic etiology in a significant number of
      cases with ID.

PMID- 24019619
TI  - Small ubiquitin-like modifier 4 M55V polymorphism is not associated with diabetic
      nephropathy in Iranian type 2 diabetes patients.
AB  - INTRODUCTION: We studied the impact of small ubiquitin-like modifier 4 (SUMO4)
      M55V polymorphism on susceptibility to diabetic nephropathy in Iranian type 2
      diabetes patients. MATERIALS AND METHODS: The patient group consisted of 50
      Iranian type 2 diabetes patients with nephropathy, and the control group
      consisted of 50 Iranian type 2 diabetes patients without nephropathy. Genotyping
      was performed using polymerase chain reaction-restriction fragment length
      polymorphism method for the M55V. RESULTS: The frequency of SUMO4 AA, AG, and GG
      genotypes were 23%, 18%, and 9% in the patient group and 10%, 22%, and 18% in the
      control group. There was no significant difference in frequency of SUMO4
      genotypes in patients compared to controls. CONCLUSION: These findings indicate
      that SUMO4 M55V polymorphism is not associated with diabetic nephropathy in
      Iranian type 2 diabetes patients.

PMID- 24019621
TI  - CD14 C-159T polymorphism and its association with chronic lung diseases: A pilot
      study on isocyanate exposed population of Central India.
AB  - CONTEXT: CD14 functions as a multifunctional receptor for bacterial cell wall
      components including endotoxin and lipopolysaccharide and is likely to influence
      the cytokine profile and subsequent immunoglobulin E production in response to
      antigen/allergen contact in allergic phenotypes. AIMS: The present study was to
      investigate genetic polymorphism in CD14 gene - 159C/T, which may be one of the
      risk factor for increased prevalence of Chronic Lung Diseases in the Central
      India. SETTINGS AND DESIGN: Survivors of Methyl isocyanates toxicity in Bhopal
      still suffering from various respiratory ailments were examined. MATERIALS AND
      METHODS: Polymerase chain reaction-restriction fragment length polymorphism was
      performed to determine the polymorphism of C-159T. RESULTS: The genotype and
      allelic frequencies were in Hardy-Weinberg's equilibrium. Prevalence of CC, CT,
      and TT were 5.5%, 22.2% and 9.25% respectively in asthmatics; 16.6%, 20.3% and
      5.5% respectively in chronic obstructive pulmonary disease (COPD) patients and
      5.5%, 14.8% and 1.85 respectively among interstitial lung disorder (ILD)
      patients; whereas the control cohort with no methyl isocyanate exposure displayed
      (CC, CT, and TT) cytosine, thymine as 2%, 1.6% and 2% respectively. Increased
      risk of Asthma among those carrying TT genotype and T allele (odds ratio [OR]
      =2.61 and 2.02 respectively). CONCLUSION: COPD risk significantly found among
      those with CC genotype and C allele (OR = 2.81 and 1.50 respectively), whereas
      ILD risk found significantly among CT genotype and C allele (OR = 1.75 and 1.40
      respectively). Therefore, single nucleotide polymorphism (SNP) C-159T
      polymorphism in CD14 gene might be a risk factor for development of CLD in this
      population.

PMID- 24019620
TI  - Analysis of methionine synthase reductase polymorphism (A66G) in Indian Muslim
      population.
AB  - BACKGROUND AND OBJECTIVES: Methionine synthase reductase (MTRR) is a vital enzyme
      of homocysteine/methionine metabolic pathway and is required for the conversion
      of inactive form of methionine synthase (MTR) to its active form. A clinically
      important allelic variant of MTRR A66G, with less enzymatic activity is reported
      with worldwide prevalence rate of ~ 30%. The present study was designed to
      determine the frequency of MTRR A66G polymorphism in rural Sunni Muslim
      population of Eastern Uttar Pradesh. MATERIALS AND METHODS: Total 56 subjects
      were analyzed for MTRR A66G polymorphism. A66G mutation analysis was carried out
      according to the polymerase chain reaction-restriction fragment length
      polymorphism method of Wilson et al. [1] amplification with MTRR specific primers
      followed by amplicon digestion with NdeI enzyme was used for the identification
      of different MTRR genotypes in subjects. RESULTS AND DISCUSSION: The AA genotype
      was found in 5 subjects, AG in 23 subjects, and GG genotype in 28 subjects.
      Genotype frequencies of AA, AG, and GG were 0.089, 0.41, and 0.5 respectively.
      The allele frequency of A allele was found to be 0.298 and G allele was 0.705.
      CONCLUSION: It is evident from the present study that the percentage of
      homozygous genotype GG and frequency of G allele is high in the target Muslim
      population.

PMID- 24019623
TI  - Proteus syndrome: Clinical profile of six patients and review of literature.
AB  - OBJECTIVE: Proteus syndrome (PS) is characterized by patchy or segmental
      overgrowth and hyperplasia of multiple tissues and organs, along with
      susceptibility to development of tumors. Very few cases are reported in
      literature from developing countries. Due to certain overlapping features with
      other overgrowth syndromes, diagnosis is usually delayed. Our aim was to describe
      clinical profile of this rare condition in six patients. MATERIALS AND METHODS:
      Retrospective case sheet review of patients followed in a Pediatric Genetic and
      Metabolic clinic at a tertiary care institute of North India with a diagnosis of
      hemihypertrophy/overgrowth syndrome. RESULTS: Six cases presented with asymmetric
      overgrowth and peculiar features suggestive of PS were included in this study.
      Age at presentation was 2 months to 10 years; two were males and four were
      females. Hemihypertrophy was noticed in only one case at birth, and focal
      overgrowths in rest of other patients were seen later during childhood.
      CONCLUSION: Due to certain overlapping features with other overgrowth syndromes,
      diagnosis of PS is usually delayed. Pediatricians are the first persons who come
      across such patients and they should be aware about this rare condition.

PMID- 24019622
TI  - Association between pediatric autoimmune neuropsychiatric disorders associated
      with streptococcal infections disease and tumor necrosis factor-alpha gene-308
      g/a, -850 c/t polymorphisms in 4-12-year-old children in Adana/Turkey.
AB  - OBJECTIVES: Pediatric Autoimmune Neuropsychiatric Disorders Associated with
      Streptococcal Infections (PANDAS) is a newly defined disease in neuropsychiatry
      and occurs with an autoimmune mechanism after Group A Beta Hemolytic
      Streptococcus (GABHS) infection. Tumor necrosis factor (TNF), encoded by TNF
      alpha gene has an important role in the apoptotic mechanisms of autoimmune
      diseases. Recently, TNF-alpha polymorphisms and autoimmune/psychiatric disorders
      have been reported to be related. In this regard, we focused on to investigate a
      possible relation between the TNF-alpha gene promoter region-308 G/A and - 850
      C/T polymorphisms and PANDAS. MATERIALS AND METHODS: In this study, ages of
      PANDAS patient and control groups were ranging from 4 years to 12-year-old.
      Patient group includes childhood onset PANDAS patients (n = 42) and control group
      includes healthy children (n = 58). Diagnoses have been carried out according to
      Diagnostic and Statistical Manual of Mental Disorder (DSM-IV) criteria with
      Affective Disorders and Schizophrenia-Present and Lifetime (KSAD-S-PL) and
      Children Yale-Brown Obsessive Compulsive Scale Moreover, PANDAS criteria
      established by the American National Psychiatry Institute have been employed for
      diagnoses. For identifying polymorphisms; Polymerase Chain Reaction, Restriction
      Fragment Length Polymorphism and Polyacrylamid Gel Electrophoresis were used.
      RESULTS AND DISCUSSION: For -308 polymorphism, 37 of 42 PANDAS patients' results
      and for -850 C/T polymorphism, 38 of 42 PANDAS patients' results were obtained.
      According to our statistical analysis there is a positive relationship between
      PANDAS patients for -308 G/A polymorphism but not for -850 C/T polymorphism.
      There is no positive relationship between -308 G/A polymorphism and antistrep
      tolysin O (ASO) titers and no relationship between -850 C/T polymorphism and ASO
      titers. We found, however, positive relationship between genders of patients
      (boys) and the disease. According to our results, we propose that the AA
      polymorphism of -308 G/A polymorphism can be used as a molecular indicator for
      PANDAS.

PMID- 24019624
TI  - Unique pattern of mutations in beta-thalassemia patients in Western Uttar
      Pradesh.
AB  - CONTEXT: beta-thalassemia is one of the most common heterogeneous inherited
      single gene disorders. The disease results from one or more of 380 different
      mutations in the beta-globin gene. Uttar Pradesh (U.P.) is the most populous
      state of India, comprising various ethnic groups and Bareilly is one of the
      largest cities situated in Western U.P. AIMS: To examine the prevalence of five
      common beta-thalassemian mutations: Intervening Sequence IVS 1-5 (c. 92 + 5 G >
      C), codon 8/9 (c. 27_28insG), codon 41/42 (c. 124_127delTTCT), IVS 1-1 (c. 92 + 1
      G > T) and codon 26 G-A (c. 79G > A) in Western U.P. SETTINGS AND DESIGN:
      Patients attending camps organized by the Thalassemia Society, Bareilly were
      selected for the study. MATERIALS AND METHODS: A total of 48 blood samples were
      collected from the patients of transfusion dependent beta-thalassemia from July
      2011 to May 2012. All the samples were analyzed for five common mutations by
      using the Amplification Refractory Mutation System (ARMS)-hot start-polymerase
      chain reaction (PCR) technique. RESULTS: Among the five common mutations
      prevalent in India, we were able to detect all except codon 26 G-A (c. 79G > A),
      which is prevalent in northeast India. These four mutations accounted for 58% of
      the total number of our patients. The IVS 1-5 (G-C) was found to be the most
      common mutation with a frequency of 46% and the 2 (nd)most common mutation was
      Fr8/9 (+G) with a frequency of 21%. The frequency of other mutations was IVS1-1
      (12%) and Cd 41/42 (4%). CONCLUSION: This study provides evidence that the
      pattern of mutations in Western U.P. is different from the rest of India and even
      from the neighboring states (Delhi and Punjab). To the best of our knowledge,
      mutation Fr8/9, the 2(nd)most common mutation in our study has never been
      reported to be so common from anywhere in India. Some mutations, which are
      prevalent in other regions are absent in our region (mutation for epsilon
      globin). Hence, these findings can be called unique to Western U.P.

PMID- 24019625
TI  - Angiotensin II type 1 receptor A1166C gene polymorphism and essential
      hypertension in Calabar and Uyo cities, Nigeria.
AB  - OBJECTIVES: The angiotensin II protein is a vasoconstrictor that exerts most of
      its influence through the angiotensin II type 1 receptor (AT1R). Inconsistent
      association between the A1166C polymorphism of the AT1R gene and hypertension has
      been reported among various populations but not among the peoples of Calabar and
      Uyo. This study was designed to determine the frequency of the A1166C
      polymorphism of the AT1R gene and its association with hypertension in a sample
      population of Calabar and Uyo. MATERIALS AND METHODS: A population-based case
      control design consisting of total of 1224 participants, 612 each of patients and
      controls were randomly recruited from hypertension clinics and the general
      population. Genotyping of the A1166C allele of the AT1R gene to identify variants
      was performed using polymerase chain reaction and restriction enzyme digestion.
      Multiple regressions were applied to test whether the A1166 genotypes were
      predictors of hypertension. RESULTS: 99% of the study population had the wild
      type AA genotype, and 1% was AC heterozygous carriers of the A1166C polymorphism.
      CONCLUSION: The A1166C polymorphism was not a predictor of hypertension in the
      sample population of Calabar and Uyo.

PMID- 24019626
TI  - Human leukocyte antigen alleles, genotypes and haplotypes frequencies in renal
      transplant donors and recipients from West Central India.
AB  - BACKGROUND: Human leukocyte antigen (HLA) is comprised of a highly polymorphic
      set of genes which determines the histocompatibility of organ transplantation.
      The present study was undertaken to identify HLA class I and class II allele,
      genotype and haplotype frequencies in renal transplant recipients and donors from
      West Central India. MATERIALS AND METHODS: HLA typing was carried out using
      Polymerase Chain Reaction-Sequence Specific Primer in 552 live related and
      unrelated renal transplant recipients and donors. RESULTS: The most frequent HLA
      class I and class II alleles and their frequencies in recipients were HLA
      AFNx0101 (0.1685) and AFNx0102 (0.1649), HLA-BFNx0135 (0.1322), and HLA-DR beta 1
      (DRB 1)FNx0115 (0.2192), whereas in donors, these were HLA-AFNx0102 (0.1848) and
      AFNx0101 (0.1667), HLA-BFNx0135 (0.1359), and HLA-DRB1FNx0115 (0.2409). The two
      locus haplotype statistical analysis revealed HLA-AFNx0102-B61 as the most common
      haplotype with the frequency of 0.0487 and 0.0510 in recipients and donors,
      respectively. Further, among the three locus haplotypes HLA-AFNx0133-BFNx0144
      DRB1FNx0107 and HLA-AFNx0102-BFNx0161-DRB1FNx0115 were the most common haplotypes
      with frequencies 0.0362 and 0.0326, respectively in recipients and 0.0236 and
      0.0323, respectively in donors. Genotype frequency revealed a high prevalence of
      genotype HLA-AFNx0102/AFNx0124 in recipients (0.058) compared to donors (0.0109)
      whereas low prevalence of HLA-AFNx0101/AFNx0102 in recipients (0.0435) than in
      donors (0.0797). The phylogenetic and principal component analysis of HLA allele
      and haplotype frequency distribution revealed genetic similarities of various
      ethnic groups. Further, case control analysis provides preliminary evidence of
      association of HLA-A genotype (P < 0.05) with renal failure. CONCLUSION: This
      study will be helpful in suitable donor search besides providing valuable
      information for population genetics and HLA disease association analysis.

PMID- 24019627
TI  - The effect of FokI vitamin D receptor polymorphism on bone mineral density in
      Jordanian perimenopausal women.
AB  - CONTEXT: Osteoporosis is a polygenic, multifactorial disease that is
      characterized by demineralization of bone, and thus presented with decreasing
      bone mineral mass. Vitamin D receptor (VDR) gene polymorphisms in the 3'-end
      region (as determined by the enzymes BsmI and ApaI) have been inconsistently
      associated with bone mineral mass. Another important VDR start codon polymorphism
      (as determined by the enzyme FokI) has been found to be related to adult bone
      mineral density (BMD) in pre-and post-menopausal American women. AIMS: This study
      aims to investigate the prevalence of the FokI VDR gene polymorphism in Jordanian
      perimenopausal women and study its relationship with bone mineral density.
      MATERIALS AND METHODS: DNA was isolated from 90 controls (Mean age = 50.41 +/-
      1.29 y), and 120 patients with symptomatic vertebral fractures (Mean age = 49.14
      +/- 3.19 y). Restriction Fragment Length Polymorphism (RFLP) analysis of FokI was
      performed on DNA samples. STATISTICAL ANALYSIS: Data was analyzed using SPSS v19
      and Microsoft Excel 2007. RESULTS: The results showed that in controls, the FF (
      0.70 +/- 0.51) genotype is associated with high lumbar spine BMD Z-score as
      compared to Ff (-1.25 +/- 0.26) and ff (-1.66 +/- 0.47) genotypes (P = 0.0095).
      In patients, the ff genotype was associated with lower lumbar spine BMD in T
      score (-2.31 +/- 0.17) and Z-score (-1.56 +/- 0.09) genotypes (P = 0.031). No
      significant association was seen in the femoral neck BMD. CONCLUSION: FokI
      polymorphism may be associated with low BMD in our studied population; however,
      further studies including other polymorphisms and large sample number are needed.

PMID- 24019628
TI  - Association between PRO12ALA polymorphism of the PPAR-gamma2 gene and type 2
      diabetes mellitus in Iranian patients.
AB  - BACKGROUND: Peroxisome proliferator-activated receptor (PPARs) have been
      identified as ligand-activated transcription factors that belong to the nuclear
      receptor superfamily. It has been shown that an association exists between
      Proline 12 alanine (Pro12Ala) polymorphism of PPAR-GAMMA2 (PPAR-gamma2) gene and
      increased risk of type 2 diabetes mellitus (T2DM) in different populations.
      Therefore, the present study was designed to investigate the association between
      Pro12Ala polymorphism of PPAR-gamma2 gene and T2DM in an Iranian population.
      MATERIALS AND METHODS: Two hundred unrelated people, including 100 healthy
      controls and 100 diabetic patients were recruited diagnosed based on American
      Diabetes Association criteria. Blood samples were used for isolation of genomic
      deoxyribonucleic acid (DNA). Having extracted the genomic DNA from human blood
      leukocytes by means of High Pure polymerase chain reaction (PCR) Template
      preparation kit, we carried out polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) on each blood sample. Then, Genomic DNA was
      digested by BstU-I restriction enzyme. Thereafter, restriction products were
      analyzed by means of Polyacrylamide gel electrophoresis and stained by Ethidium
      Bromide. RESULTS: We found that the frequency of Ala allele in healthy subjects
      was significantly higher than in diabetic subjects (P = 0003). Moreover, the
      genotype frequency of Ala/Ala in healthy subjects was significantly higher than
      in diabetic subjects (P < 0.001). However, the genotype frequency of Ala/Pro in
      diabetic subjects was significantly higher than in healthy subjects (P < 0.001).
      CONCLUSION: The present study suggests that polymorphism of PPAR-gamma2 gene is
      associated with T2DM. Furthermore, Ala allele is significantly found in non
      diabetic individual's Iranian population.

PMID- 24019629
TI  - Genetic and environmental effects on age at menarche, and its relationship with
      reproductive health in twins.
AB  - INTRODUCTION: Menarche or first menstrual period is a landmark in reproductive
      life span and it is the most prominent change of puberty. The timing of menarche
      can be under the influence of genes as well as individual environmental factors
      interacting with genetic factors. OBJECTIVE: Our study objectives were (a) to
      investigate the heritability of age of menarche in twins, (b) to obtain the
      association between age of menarche and childhood factors, and reproductive
      events/behavior, (c) to examine whether or not having a male co-twin affects
      early/late menarche. METHODOLOGY: A group of female-female identical (n = 108, 54
      pairs), non-identical twins (n = 68, 34 pairs) and 17 females from opposite-sex
      twin sets were identified from twin registries of Malaysia and Iran. Genetic
      analysis was performed via two methods of Falconers' formula and maximum
      likelihood. RESULTS: Heritability was found to be 66% using Falconers' formula
      and 15% using univariate twin analysis. Model analysis revealed that shared
      environmental factors have a major contribution in determining the age of
      menarche (82%) followed by non-shared environment (18%). DISCUSSION: Result of
      this study is consistent with that of the literature. Timing of menarche could be
      under the influence of shared and non-shared environmental effects. Hirsutism was
      found to have a higher frequency among subjects with late menarche. There was no
      significant difference in age of menarche between females of opposite-sex twins
      and females of same-sex twins. CONCLUSION: It is concluded that twin models
      provide a powerful means of examining the total genetic contribution to age of
      menarche. Longitudinal studies of twins may clarify the type of environmental
      effects that determine the age of menarche.

PMID- 24019630
TI  - Comparison of in-vitro and in-vivo response to fetal hemoglobin production and
      gamma-mRNA expression by hydroxyurea in Hemoglobinopathies.
AB  - BACKGROUND: Hydroxyurea, which induces Fetal hemoglobin (HbF) synthesis, is the
      only drug widely used in different hemoglobinopathies; however, the response is
      very variable. We compared the efficacy of hydroxyurea in-vitro in erythroid
      cultures and in-vivo in the same patients with different hemoglobinopathies to
      induce HbF production and enhance gamma-messenger RNA expression. MATERIALS AND
      METHODS: A total of 24-patients with different Hemoglobinopathies were given
      hydroxyurea and their response was studied in-vivo and in-vitro on mononuclear
      cells collected from them simultaneously. RESULTS: A total of 57.7% of patients
      (responders) showed no further crisis or transfusion requirements after
      hydroxyurea therapy with a mean increase in fetal cells (F-cells) of 63.8 +/-
      59.1% and gamma-mRNA expression of 205.5 +/- 120.8%. In-vitro results also showed
      a mean increase in F-cells of 27.2 +/- 24.7% and gamma-mRNA expression of 119.6%
      +/- 65.4% among the treated cells. Nearly 19.0% of the partial-responders reduced
      their transfusion requirements by 50% with a mean increase in F-cells of 61.2 +/-
      25.0% and 28.4 +/- 25.3% and gamma-mRNA-expression of 21.0% +/- 1.4% and 80.0% +/
      14.1% in-vivo and in-vitro respectively. The non-responders (15.3%) showed no
      change in their clinical status and there was no significant increase in F-cells
      levels and gamma-mRNA expression in-vivo or in-vitro. CONCLUSION: Thus, this
      method may help to predict the in-vivo response to hydroxyurea therapy; however,
      a much larger study is required.

PMID- 24019631
TI  - Early diagnosis of co-existent beta-thalassemia and alkaptonuria.
AB  - Since the aggregate incidence of inborn errors of metabolism is relatively high,
      a high degree of suspicion is essential to correctly diagnose an inborn error of
      amino acid metabolism. We report a case of alkaptonuria an autosomal recessive
      disorder that occurs due to deficiency of homogentisic acid oxidasein a beta
      thalassemia infant presenting with reddish discoloration of nappies and clothes,
      breath holding spells, and microcytic hypochromic anemia. Born to consanguineous
      cousins, to our knowledge, the combination of beta-thalassemia and alkaptonuria,
      which we have described in this baby, has not been reported earlier. 

PMID- 24019632
TI  - Derivative chromosome 11 in a child resulting from a complex rearrangement
      involving chromosomes 3, 6 and 11 in father: Significance of parental
      karyotyping.
AB  - The presence of derivative chromosome in a child with phenotypic features
      necessitates the need of parental karyotyping to ascertain the exact amount of
      loss or gain of the genetic material. The aim of this study was to emphasize the
      importance of parental karyotyping. Cytogenetic evaluation of the proband and his
      father were carried out at Laboratory. Cytogenetic analysis was performed on
      phytohemagglutinin stimulated cultures. The derivative chromosome 11 in proband
      was ascertained to have additional material from chromosome 6p arising from
      complex chromosomal rearrangement in the father. Karyotyping is the basic, cost
      effective preliminary investigation in a child with mental subnormality or
      congenital anomalies. 

PMID- 24019633
TI  - A case of Kartagener's syndrome: Importance of early diagnosis and treatment.
AB  - Kartagener's syndrome is a very rare congenital malformation comprising of a
      classic triad of sinusitis, situs inversus and bronchiectasis. Primary ciliary
      dyskinesia is a genetic disorder with manifestations present from early life and
      this distinguishes it from acquired mucociliary disorders. Approximately one half
      of patients with primary ciliary dyskinesia have situs inversus and, thus are
      having Kartagener syndrome. We present a case of 12 year old boy with sinusitis,
      situs inversus and bronchiectasis. The correct diagnosis of this rare congenital
      autosomal recessive disorder in early life is important in the overall prognosis
      of the syndrome, as many of the complications can be prevented if timely
      management is instituted, as was done in this in this case. 

PMID- 24019635
TI  - Micro-RNAs in IVF outcome.

PMID- 24019634
TI  - Sclerosterosis (Truswell-Hansen disease).
AB  - Sclerosteosis or Truswell-Hansen disease is a rare autosomal recessive disorder
      characterized by dense bones, tall stature, and syndactyly. Most of the reports
      are from South Africa. Here we report the first such case from India. 

PMID- 24019636
TI  - Large scale meta-analysis of genetic studies in ischemic stroke: Five genes
      involving 152,297 individuals.

PMID- 24019637
TI  - Effect of the novel Moroccan BRCA1 and BRCA2 frameshift mutations.

PMID- 24019638
TI  - Present scenario of Journal of Indian Association of Pediatric Surgeons.

PMID- 24019639
TI  - Modified koyanagi repair for severe hypospadias.
AB  - AIM: To report the results of an early series of patients who underwent modified
      Koyanagi repair for severe hypospadias. MATERIALS AND METHODS: A total of 24 boys
      (age: 9 months to 11 years) with proximal hypospadias, chordee, and poor urethral
      plate underwent modified Koyanagi repair between September 2008 and January 2012.
      Nine boys had associated penoscrotal transposition that was corrected
      simultaneously. Vascularized parameatal based foreskin flap was used to correct
      the hypospadias in a single stage. The follow-up ranged from 6 months to 3.5
      years. RESULTS: A total of 13 of the 24 children had a good outcome and were
      voiding normally, while 11 boys developed complications, 3 of which were major
      and 8 minor. The major complications were complete breakdown (n = 1), meatal and
      distal neourethral stenosis requiring laying open of distal urethra (n = 1), and
      glans breakdown (n = 1). The minor complications included fistulae (n = 5),
      meatal stenosis amenable to dilatation (n = 1), and lateral chordee (n = 1).
      Majority of the complications were in the initial patients, with successful
      outcomes in the last 1 year. Most of these complications were successfully
      managed by minor second procedures. CONCLUSION: Modified Koyanagi repair not only
      corrects severe hypospadias with chordee but also corrects the associated
      penoscrotal transposition in a single stage. The results are good once the
      learning curve is crossed.

PMID- 24019640
TI  - Y-type urethral duplication in children: Management strategy at our center.
AB  - AIMS: Report of seven children with Y-type urethral duplication (YUD). MATERIALS
      AND METHODS: (A) Four staged operations were performed in patients having
      extensive perineal dissection (for rectourinary fistula separation and anterior
      mobilization of ventral urethra (VU)), tension rectocutaneous anastomosis, and
      children who were not toilet trained). These stages are (1) diversion sigmoid
      colostomy with anterior mobilization of VU as perineal urethrostomy via anterior
      sagittal approach; (2) Orthotopic urethral (OU) reconstruction; (3) anastomosis
      of OU and perineal urethra; (4) colostomy closure with management of
      complications. (B) The patients having VU onto the perineum underwent single
      stage urethral reconstruction. RESULTS: The VU was urethrorectal/urethroanal in
      five and urethroperineal in two. Low anorectal malformation and upper urinary
      tract anomalies were present in 57.1% (4/7) and 14.7% (1/7) patients,
      respectively. Buccal mucosa free graft, transverse inner preputial flap, and
      perineal skin were tubularized for OU reconstruction. Mean age at 1(st) , 2(nd) ,
      3(rd) , and 4(th) surgery was 5 +/- 0.78, 28 +/- 0.78, 36 +/- 0.78, 49 +/- 0.78
      months respectively. Three patients needed surgery for complications
      (urethrocutaneous fistula in two and urethral diverticulum in one) in a mean 3.12
      +/- 0.34 years of follow-up. Final uroflowmetry and fecal continence were good in
      all patients. CONCLUSIONS: The YUD is a difficult entity to manage. Although,
      staged procedure appears to be time consuming, but good and promising results can
      be achieved by staging the procedure.

PMID- 24019641
TI  - Management of child victims of acute sexual assault: Surgical repair and beyond.
AB  - AIM: To evaluate the outcome of definitive repair of anogenital injuries (AGI) in
      child victims of acute sexual assault. SETTINGS AND DESIGN: It is a prospective
      study of emergency care provided to child victims of acute sexual assault at a
      tertiary care Pediatric Surgical Unit in Maharashtra, India. MATERIAL AND
      METHODS: Out of 25 children, who presented during January 2009-December 2010 with
      suspected sexual assault, five children (one male and four female, between 4-9
      years of age), had incurred major AGI. These children underwent definitive repair
      and a diverting colostomy. Perineal pull-through was performed in the male child
      with major avulsion of rectum. One 4-year-old girl with intraperitoneal vaginal
      injury required exploratory laparotomy in addition. RESULTS: The postoperative
      period and follow-up was uneventful in all our patients. Four out of five
      patients have excellent cosmetic and functional outcome with a follow-up of 2-4
      years. Our continence results are 100%. CONCLUSION: Children with acute sexual
      assault need emergency care. To optimally restore the distorted anatomy, all
      major AGI in such children should be primarily repaired by an expert, conversant
      with a child's local genital and perineal anatomy. Along with provision of
      comprehensive and compassionate medical care, prevention of secondary injuries
      should be the ultimate goal.

PMID- 24019642
TI  - Giant anterior urethral diverticulum with a calculus masquerading as left
      inguinal hernia: A missed diagnosis, a lesson to learn.
AB  - Congenital anterior urethral diverticulum is an infrequent but important cause of
      infravesical obstructive uropathy in children. Clinical spectrum usually includes
      obstructive or irritative urinary symptoms or penile ballooning during the act of
      micturition. We share our experience in a case of giant anterior urethral
      diverticulum with a contained calculus presenting as a huge inguino-scrotal
      swelling and masquerading as left inguinal hernia. The fluctuation in the size of
      the swelling related to the act of micturition was mistaken for cough impulse. He
      was subjected to a left inguinal herniotomy, following which he developed urine
      leak from the surgery wound and was subsequently referred to our centre for
      further management. The importance of a detailed history, meticulous physical
      examination, and diagnostic imaging has been stressed. The surgical approach in
      such cases has also been highlighted. 

PMID- 24019643
TI  - Metanephric stromal tumor: An unusual pediatric renal neoplasm.
AB  - A renal tumor in a 14-month- old child, who was initially diagnosed as
      mesoblastic nephroma, but on review post surgery was diagnosed as hyper
      differentiated metanephric stromal tumor, with its excellent prognostic outcome.
      An attempt is made to document imaging features that may enable one to suspect
      this rare condition. The literature is reviewed with emphasis on its distinction
      from its look-alikes in the pediatric age group. 

PMID- 24019645
TI  - Successful management of a renal fungal ball in a pretermature neonate: A case
      report and review of literature.
AB  - Invasive fungal infection is common in the present day NICUs - generally
      manifesting as candiduria or candida sepsis. Fungal balls in the kidneys are very
      uncommon and most are amenable to higher antifungal agents. However, we had a
      child who did not respond to such measures and ultimately needed a surgical
      removal of the fungal ball in his kidney. We report this case along with a review
      of literature to highlight about this uncommon, but an important cause of
      persistent sepsis in pre-term infants and to review the treatment options
      including a surgical removal. 

PMID- 24019644
TI  - Intestinal obstruction in a premature baby: Endoscopic diagnosis and management
      by minimal access surgery.
AB  - Neonatal intestinal obstruction is the most common surgical emergency in a
      newborn. Although, large numbers of newborns are operated in our country, limited
      published literature is available on advances in diagnosis, and management of
      this problem with outcome analysis in newborns. We report a premature (32 weeks)
      newborn who developed acute onset symptoms of small bowel obstruction in
      3(rd)week of life, and discuss the approach to diagnosis and management with the
      minimal access surgery and successful outcome. 

PMID- 24019646
TI  - Aortoesophageal fistula in a child.
AB  - Aortoesophageal fistulae (AEF) are rare and are associated with very high
      mortality. Foreign body ingestions remain the commonest cause of AEF seen in
      children. However in a clinical setting of tuberculosis and massive upper GI
      bleed, an AEF secondary to tuberculosis should be kept in mind. An early strong
      clinical suspicion with good quality imaging and endoscopic evaluation and timely
      aggressive surgical intervention helps offer the best possible management for
      this life threatening disorder. Our case is a 10-year-old boy who presented to
      the pediatric emergency with massive bouts of haemetemesis and was investigated
      and managed by multidisciplinary team effort in the emergency setting. 

PMID- 24019647
TI  - Meckel's diverticulum at uncommon mesenteric location.

PMID- 24019648
TI  - Corkscrew vessels: Is it a predictor of vanishing testis syndrome?

PMID- 24019649
TI  - Magnetic resonance imaging and positron emission tomography-computed tomography
      evaluation of soft tissue sarcoma with surgical and histopathological
      correlation.
AB  - PURPOSE: The aim of this study was to evaluate the role of positron emission
      tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI) in
      characterization and pre-operative staging of soft-tissue sarcoma (STS) and
      correlating with operative and histopathological findings. MATERIALS AND METHODS:
      Twenty patients (age range 16-72 years [mean 44.4 years]) with resectable and STS
      were included in this prospective study. Pre-operative MRI was carried out in all
      patients with acquisition of T1W, T2W, and short tau inversion recovery (STIR)
      sequences in appropriate planes. Contrast enhanced MRI was performed in four
      patients. Whole body PET-CT was performed in 13 patients. Demographic data,
      clinical features, pre-operative imaging analysis, operative, and
      histopathological findings were analyzed using SPSS software version 11.5.
      RESULTS: The most common histologic type was malignant fibrous histiocytoma (MFH)
      (30%). Of 18 STSs 20 were high-grade. Agreement existed between MR and operative
      size. MRI had 100% negative predictive value (NPV) in predicting neurovascular
      bundle involvement. However, positive predictive value (PPV) was 33%. MRI had PPV
      of 20% while PET-CT had 50% PPV in detecting lymph node involvement. Overall
      staging accuracy of MRI was 75% when correlated with surgical and
      histopathological findings. Combined PET-CT and MRI staging, in 13 patients, was
      better (92.31%) when compared with staging with MRI (84.62%). Specific diagnosis
      on image characteristics was correctly suggested in 35% patients. CONCLUSIONS:
      MRI is the robust modality in local staging of STSs and PET-CT adds greater
      accuracy to overall staging in combination with MRI.

PMID- 24019650
TI  - Role of Tc99m-Sestamibi scintimammography in assessing response to neoadjuvant
      chemotherapy in patients with locally advanced breast cancer.
AB  - INTRODUCTION: Neoadjuvant chemotherapy (NACT) is an essential part of multi
      disciplinary management of locally advanced breast cancer (LABC). In this study,
      we aimed at evaluating the role of Tc99m-Sestamibi scinti-mammography in
      assessing response to NACT in patients with LABC. MATERIALS AND METHODS: A total
      of 42 patients of histologically proven LABC were enrolled in this prospective
      study. Imaging was performed according to pre-defined protocol at 10 min and 4 h
      after injection of tracer before the start of chemotherapy, 48 h after start of
      chemotherapy and at the end of chemotherapy. Quantitative parameters were
      obtained by calculating the ratio of activity in a region of interest (ROI) drawn
      over the tumor and the same sized ROI drawn in corresponding location in contra
      lateral breast. RESULTS: At the end of chemotherapy, 6 patients achieved complete
      response, 25 achieved partial response, 11 had stable disease. Various retention
      indices calculated at baseline, 48 h after first cycle of NACT, and at the end of
      chemotherapy showed statistically significant difference in responders and non
      responders. By using 84.05 as cut-off point for retention index (RI) of tumor
      calculated 48 h after first cycle of NACT (RI 2) the positive predictive value
      and negative predictive value, were found to be 41.9% and 72.7% respectively in
      differentiating responders from non-responders. CONCLUSION: Early response
      assessment in patients with LABC to NACT with Tc99m-Sestamibi scintimammography
      is feasible and if confirmed by further studies can find routine clinical
      application in differentiating responders from non-responders.

PMID- 24019651
TI  - Role of lymphoscintigraphy in diagnosis and management of patients with leg
      swelling of unclear etiology.
AB  - BACKGROUND: To study the utility of lymphoscintigraphy in detection of lymphatic
      obstruction in patients with leg swelling of unclear etiology, selection of site
      for nodo venous shunt procedure, and follow-up lymphoscintigraphic documentation
      of improved lymph flow in surgically treated limb. MATERIALS AND METHODS: Twenty
      four consecutive patients with leg swelling, 10 male, 14 female with mean age 47
      years, range from 13 years to 74 years underwent lymphoscintigraphy. All patients
      were referred from Department of Plastic Surgery, after initial work-up, and
      routine investigations to rule out the other causes of leg swelling. Both
      clinical and scintigraphic staging performed for all patients. All clinically and
      scintigraphically positive patients treated with decongestive lymphatic therapy
      (DLT). In addition to the DLT, those patients positive for unilateral or
      bilateral lymphedema, consented for surgical intervention, nodo venous shunt
      (NVS) in their only affected or one of the two affected lower limbs. Follow-up
      lymphoscintigraphy performed in operated cases after 3 months to 6 months of
      surgery, lymphoscintigraphy images of each patient in pre and post-surgery
      compared. RESULTS: In 20/24 cases (83%) of clinically positive leg swelling were
      found to be positive for lymphedema on lymphoscintigraphy and remaining, 4/24
      were scintigraphically normal. Based on the clinical and lymphoscintigraphy
      staging, 03/20 cases (15%) had Grade I lymphedema, 01/20 (5%) Grade II
      lymphedema, 06/20 (30%) Grade III and remaining 10/20 (50%) had Grade IV
      lymphedema. 11/20 cases of Lymphedema (55%) were managed conservatively by only
      DLT and in remaining 09/20 cases (45%), who were case of Grade IV, lymphedema
      (five patients with unilateral and four patients with bilateral disease)
      initially treated with DLT, and on completion of DLT, undergone for NVS
      procedure, in their unilaterally affected lower limb or one of the two diseased
      lower limbs. All nine patients showed remarkable clinical improvement in leg
      swelling and their follow-up lymphoscintigraphy showed normal visualization of
      lymphatic channels. No patient developed any recurrence. CONCLUSION: Pre
      operative functional evaluation of lymphatic channels using lymphoscintigraphy,
      is a widely available, simple imaging test and highly useful for documentation of
      lymphedema in patients with leg swelling of unclear etiology and also for exact
      localization of inguinal lymph nodes to perform the NVS procedure. Further, it
      can play important role for follow-up of patients receiving DLT or DLT with
      surgical intervention that provides early relief from clinical symptoms.

PMID- 24019652
TI  - Role of cholescintigraphy in management of acute acalculous cholecystitis.
AB  - AIM: This study is aimed to evaluate the role of cholescintigraphy in management
      of acute acalculous cholecystitis. MATERIALS AND METHODS: A total of thirty two
      patients who had presented to the surgical out-patient department or referred
      from in-patient department or intensive care unit between February 2008 and
      February 2010 were studied. All patients with Ultrasonography abdomen findings of
      acalculous cholecystitis were included in the study and they underwent
      cholescintigraphy. Gall bladder ejection fraction (GBEF) was calculated 30 min
      after fatty meal. Patients who either had non-visualization of gall bladder or
      GBEF less than 40% were considered to have acalculous cholecystitis on
      cholescintigraphy. The patients were followed-up for a period of 3 months after
      the commencement of treatment. RESULTS: Eleven patients had either non
      visualization of gall bladder or GBEF < 40%. Of these, six patients underwent
      cholecystectomy and the rest were medically managed, as patients deferred
      surgery. 83.33% of post-cholecystectomy patients as against 40% of medically
      treated patients were symptom free. Twenty one patients had GBEF > 40%, 90.74% of
      these patients were symptom free at the end of 3 months, with medical management.
      CONCLUSION: Cholescintigraphy is an important adjunct in management of patients
      with acalculous cholecystitis by guiding the course of therapy-surgical
      management versus medical management.

PMID- 24019653
TI  - Radiomodulatory role of Rutin and Quercetin in Swiss Albino mice exposed to the
      whole body gamma radiation.
AB  - CONTEXT: Radiation therapy is the prime treatment modality against various
      cancers. However, its use is limited due to the effects of radiation on normal
      tissues. AIMS: In view of this, present study was carried out to evaluate the
      radioprotective potential of Rutin (RUT) and Quercetin (QRT) in Swiss Albino mice
      exposed to the whole body gamma radiation. To gain insight into the mechanism of
      action, RUT and QRT were tested for its antioxidant levels in mice. SETTINGS AND
      DESIGNS: Optimum protective dose of RUT and QRT against radiation induced animal
      mortality was selected by administration of various doses of the RUT and QRT
      before 10 Gy gamma irradiation. MATERIALS AND METHODS: Swiss Albino mice were
      used for the assessment of radiation induced sickness along with the survival
      analysis and anti-oxidative properties of RUT and QRT. STATISTICAL ANALYSIS USED:
      Survival studies were determined using the Kaplan-Meier survival curves. RESULTS:
      The maximum survival was observed with 10 mg/kg. b. wt. and 20 mg/kg. b. wt. of
      RUT and QRT respectively, this dose was considered as an optimal dose for
      radioprotection. Treatment of mice with RUT and QRT before irradiation delayed
      the onset of mortality as compared with the untreated irradiated controls. The
      oral administration of RUT and QRT resulted in an increase in the radiation
      tolerance and the dose reduction factor was found to be 1.15 and 1.11
      respectively. RUT and QRT pre-treatment significantly (P < 0.01) elevated levels
      of reduced glutathione, glutathione-S-transferase, catalase, Superoxide
      dismutase, and a decreased lipid peroxidation in mouse liver homogenate at 24 h
      after exposure to 4.5 Gy. CONCLUSIONS: Present findings demonstrate the potential
      of RUT and QRT in mitigating radiation-induced mortality, which may be attributed
      to the elevation in the antioxidant status, anti-lipid peroxidative potential.

PMID- 24019654
TI  - Radiation surveillance in and around cyclotron facility.
AB  - The cyclotron is the most widely used particle accelerator for producing
      medically important radio nuclides. Many medical centers in India have installed
      compact medical cyclotrons for on-site production of short-lived positron
      emitting radio nuclides such as (18)F, (13)N, and (11)C. A mandatory requirement
      for cyclotron installation is radiation control permit from Atomic Energy
      Regulatory Board. Cyclotron radiation survey is an integral part of the overall
      radiation safety in the cyclotron facility. Radiation surveillance in and around
      a newly installed cyclotron was performed using ionization chamber counter and
      Geiger Muller counter before, during and after operating the cyclotron. The
      readings were recorded at various locations where a high radiation field was
      expected. The results were recorded, tabulated and analyzed. The highest exposure
      level (0.93 MUSv) was found at the back wall of the radiochemistry lab facing the
      cyclotron vault. Reason for the high exposure of 0.93 MUSv/h: Synthesis of (18)F
      Fluoro-Deoxy-Glucose ((18)F-FDG) was going in the synthesis module and activity
      ((18)F) was present in the synthesis module when reading was taken. All other
      values were found to be below the recommended levels of exposure. 

PMID- 24019655
TI  - Iodine-131MIBG SPECT/CT in neuroendocrine tumours: An institutional experience.
AB  - CONTEXT: Radiolabelled metaiodobenzylguanidine (MIBG) is commonly used for
      imaging of neuroendocrine tumors (NETs). The hybrid imaging with single photon
      emission computerized tomography/computerized tomography (SPECT/CT) co
      registration can give that additional edge to this functional imaging modality.
      AIMS: To study the additional value of (131)I-MIBG SPECT/CT scintigraphy in
      evaluation of NETs. SETTINGS AND DESIGN: We performed a retrospective study of
      the scintigraphic data of patients referred to our department for detection and
      follow-up of NETs from 2004 to 2008. MATERIALS AND METHODS: Total number of
      studies were 370. Twenty-eight patients with equivocal findings on planar imaging
      had undergone additional SPECT/CT imaging. The contribution made by SPECT/CT
      imaging in these studies was analyzed. RESULTS: In 27 of 28 cases, SPECT/CT
      provided vital additional information. CONCLUSIONS: We concluded that SPECT/CT co
      registration helps in exclusion, identification, and localization of primary and
      metastatic NETs. It differentiates physiological from pathological tracer
      distribution. It helps increase the confidence in reporting, especially in
      equivocal findings on planar imaging.

PMID- 24019656
TI  - Association of non-traumatic complex regional pain syndrome with adenocarcinoma
      lung on 99mTc-MDP bone scan.
AB  - Complex regional pain syndrome (CRPS) is usually associated with trauma. Rarely,
      it may be seen in association with malignancies. We present here the bone scan
      and X-ray findings in the case of a 56-year-male-patient with adenocarcinoma lung
      who also had non-traumatic CRPS without involvement of the stellate ganglion. The
      case highlights the fact that spontaneous development of reflex sympathetic
      dystrophy may be associated with a neoplastic etiology. 

PMID- 24019657
TI  - Myocardial perfusion scintigraphy in a case of dextrocardia: Doing it "right".
AB  - We present the challenges in performing the stress test and acquisition of images
      in myocardial scintigraphy in a 54-year-old female patient with dextrocardia.
      Dextrocardia and situs inversus were documented on prior investigations including
      a chest roentgenogram and sonography. 

PMID- 24019658
TI  - Simultaneous occurrence of Graves' disease in eutopic and ectopic thyroid
      tissues: A case report and review of literature.
AB  - Ectopic thyroid tissue an uncommon condition results from abnormal migration of
      the primitive thyroid bud. This may be the only functional thyroid. Ectopic
      thyroid tissue may sometimes coexist with the eutopic thyroid gland.
      Hyperthyroidism in association with ectopic thyroid tissue is very uncommon. We
      report a rare case of simultaneous involvement of ectopic and eutopic thyroid
      tissue in a married women of 35 years who was referred to our department for a
      technetium 99m thyroid scan. Coexisting ectopic and eutopic thyroid tissue due to
      identical histology may have similar response to various stimulatory and
      inhibitory factors like hormones and immunoglobulin's. Iodine-131 is an easy to
      administer and effective treatment for patients with simultaneous Graves' disease
      in the ectopic and eutopic thyroid tissues. 

PMID- 24019659
TI  - Vicarious visualization of gall bladder on Tc-99m ethylene dicysteine renal
      dynamic study.
AB  - Though the hepatobiliary excretion of Technetium-99m ethylene dicysteine (99mTc
      EC) is very low and usually does not effect image interpretation on routine
      posterior imaging, the possibility of visualization of the gall bladder should be
      kept in mind while reporting the 99mTc-EC scan especially, when anterior imaging
      is performed as in renal transplant patients. 

PMID- 24019660
TI  - FDG PET/CT in a rare case of multiple cutaneous metastases in carcinoma larynx.
AB  - Distant metastases in squamous cell carcinoma of the larynx have an incidence of
      6.5-7.2% and most commonly involves the lungs, liver, and bone. Metastases to the
      skin are very rare, but, when present, they are usually considered a poor
      prognostic sign. This most often affect the supradiaphragmatic area, i.e., the
      head, neck, thorax, or upper extremities. We have reported 18F-fluorodeoxyglucose
      positron emission tomography computed tomography (FDG PET/CT) scan of a patient
      with squamous cell carcinoma of the larynx showing multiple subcutaneous nodules
      all over the body, which was helpful in the assessment as well as staging of the
      disease. 

PMID- 24019661
TI  - Recurrent giant cell tumor of foot detected by F18-FDG PET/CT.
AB  - Detection of recurrence of tumors with conventional imaging like computed
      tomography (CT) and magnetic resonance imaging (MRI) can be difficult because of
      distorted anatomy and implants in situ. Fluorine-18 fluorodeoxyglucose positron
      emission tomography/computed tomography (F-18 FDG PET/CT has been shown to be
      very useful in detection of recurrent tumors with higher accuracy than
      conventional imaging method. Giant cell tumors of foot though rare have high
      recurrence potential after initial curative treatment. However, currently there
      is no literature addressing the role of F-18 FDG PET/CT in evaluation of these
      tumors. We report a case of post excisional recurrent giant cell tumor of foot
      diagnosed on F-18 FDG PET/CT. In addition, to detection of recurrence F-18 FDG
      PET/CT also aided in accurate management of the patient. 

PMID- 24019662
TI  - Incidentally detected grade 3 cystocele on FDG PET/CT in a case of suspected
      malignancy.
AB  - Unexpected findings are seen on FDG PET/CT outside the primary site of
      abnormality. Such incidental findings are common in the genitourinary tract due
      to normal urinary excretion of FDG. We report a case of incidentally detected
      grade 3 cystocele in a patient who underwent FDG PET/CT study for a suspected
      lung malignancy. 

PMID- 24019663
TI  - Duplicated gall bladder detected on 99m Tc HIDA hepatobiliary scintigraphy: A
      report of two cases.
AB  - Gall bladder (GB) duplication is a rare condition often found incidentally; most
      of these detected on screening Ultrasonography (USG) for abdominal colic. Nuclear
      hepatobiliary scan, popularly known as hepatobiliary iminodiacetic acid (HIDA)
      scan, with its biliary kinetics, is highly specific for picking up abnormalities
      related to biliary tract and GB. We report two cases of duplication of GB
      visualized on HIDA scan. First case highlights the role of HIDA scan in diagnosis
      of duplicated GB, where USG was equivocal with a number of differentials, whereas
      in the second case, HIDA helped to rule out obstruction in this case of
      duplicated GB identified on USG; ruling out biliary cause for the abdominal
      colic. 

PMID- 24019664
TI  - Incidental detection of a bleeding gastrointestinal stromal tumor on Tc-99m red
      blood cell scintigraphy.
AB  - The role of 99m-technetium labeled red blood cell (RBC) scintigraphy in acute
      gastro-intestinal bleed is well-established. The authors report a case of a
      bleeding gastrointestinal stromal tumor (GIST) incidentally discovered on Tc-99m
      RBC scintigraphy. 

PMID- 24019665
TI  - Hyperostosis fronto-parietalis mimicking metastasis to the skull: Unveiled on
      SPECT/CT.

PMID- 24019666
TI  - A Logical levothyroxine dose Individualization: Optimization Approach at
      discharge from Radioiodine therapy ward and during follow-up in patients of
      Differentiated Thyroid Carcinoma: Balancing the Risk based strategy and the
      practical issues and challenges: Experience and Views of a large volume referral
      centre in India.
AB  - In this communication, the authors discuss the issue of individualization of
      thyrotropin suppressive therapy in differentiated thyroid carcinoma (DTC)
      patients and share their views with respect to optimizing the dose of
      levothyroxine (LT) prescription both during discharge from radioiodine therapy
      ward and during follow-up. The changing management paradigm at our Institute
      during post-thyroidectomy period and during the preparation for radioiodine scan
      is also briefly highlighted. Five factors can be identified as important
      determinants for the dose individualization approach: (1) Persistence or absence
      of metastatic disease, (2) the risk characteristics of the patient and the tumor
      (3) patient's clinical profile, symptomatology, and contraindications (4) the
      feasibility to ensure a proper thyroid stimulating hormone TSH suppression level
      (depends on patient's socio-economic and educational background, the connectivity
      with the local physician and his expertise) (5) time period elapsed since initial
      diagnosis. While discussing each individual case scenario, the authors, based
      upon their experience in one of the busiest thyroid cancer referral centers in
      the country, discuss certain unaddressed points in the current guideline
      recommendations, deviations made and some challenges toward employing them into
      practice, which could be situation and center specific. In addition to these, the
      value of clinical examination, patient profile and detailed enquiry about
      clinical symptomatology by the attending physician in each follow-up visit cannot
      be overemphasized. According to the authors, this aspect, quite important for
      dose determination in an individual, is relatively underrepresented in the
      present guidelines. It would also be worthwhile to follow a conservative approach
      (till clear data emerges) in patients who have characteristics of "high-risk"
      disease, but are clinically and biochemically disease free, if no medical
      contraindications exist and patient tolerates the suppressive therapy well. This
      would be particularly applicable in the presence of aggressive histopathological
      variants, where, in the event of recurrence/metastasis, the disease demonstrates
      adverse prognosis and higher incidence of radioiodine refractoriness. At the end,
      certain important and noteworthy concepts pertaining to LT prescription that has
      definitive practical implications for the suppressive therapy in DTC patients are
      described. 

PMID- 24019667
TI  - Parathyroid scintigraphy, histopathology correlation in patients with tropical
      pancreatitis and coexisting primary hyperparathyroidism.
AB  - PURPOSE: Tropical pancreatitis (TP) is a juvenile, non-alcoholic type of chronic
      pancreatitis and is highly prevalent in Kerala, India. Increasing prevalence of
      TP and its varied manifestations prompted us to undertake this retrospective
      analysis. We attempted to study the incidence of TP in patients with primary
      hyperparathyroidism (PHPT) and correlate with calcium levels, scintigraphy and
      histopathology findings. MATERIALS AND METHODS: Records of 44 hypercalcemic
      patients with raised parathormone (PTH) were analyzed. Clinical, biochemical and
      imaging findings were noted to look for diabetes mellitus and pancreatitis. All
      patients underwent dual phase (99m) Technetium methoxy isobutyl isonitrile
      parathyroid scintigraphy in our department between January 2007 and 2010. Gamma
      probe assisted minimally invasive parathyroidectomy was performed.
      Histopathological correlation was obtained in all patients. RESULTS: Our study
      shows 18% (8/44 patients) incidence of TP in patients with PHPT (compared to 7%
      reported in 1970's) in Kerala. Results show involvement of middle aged, non
      alcoholic males. No direct association between severity of diabetes, pancreatitis
      and PHPT was noted in our series. Parathyroid adenoma was the most common
      underlying pathology. All TP patients' clinical outcome improved post
      parathyroidectomy. TP patients with PHPT demonstrated adenomas, mainly composed
      of oxyphilic cells. Non pancreatitis group interestingly showed a varied picture
      of adenoma, hyperplasia with predominance of chief cells histologically.
      CONCLUSION: There is a 2.6 fold increase in the incidence of TP (18%) in patients
      with PHPT. Hypercalcemia may be the causative factor leading to TP in PHPT
      patients in our limited series. The data suggests a causal association between
      pancreatitis and PHPT. Patients presenting with either one or a combination of
      hypercalcemia, pancreatic dysfunction or raised PTH need to be thoroughly
      evaluated as their management is interlinked.

PMID- 24019668
TI  - Usefulness of asymmetry score on quantitative three-phase bone scintigraphy in
      the evaluation of complex regional pain syndrome.
AB  - INTRODUCTION: Complex regional pain syndrome (CRPS) is primarily a clinical
      diagnosis. Diagnostic imaging in CRPS can be used, especially to exclude other
      disorders. The sensitivity and specificity of three phase bone scintigraphy
      (TPBS) for the diagnosis of CRPS is variable throughout the literature. AIM: To
      establish a simple and effective quantitative approach to help in the diagnosis
      of CRPS by TPBS. MATERIALS AND METHODS: TPBS done in patients (n = 68) with
      suspected CRPS was analyzed retrospectively. They were classified into bone scan
      positive group (BSP), bone scan negative group (BSN) and non-CRPS group based on
      diffusely increased periarticular uptake, symmetrical uptake, and focal uptake
      respectively. Asymmetry score (AS) was also measured between the affected and
      unaffected side. RESULTS: 16 patients showed focal uptake, 37 were in BSP group
      with mean AS score of 1.57 +/- 0.5 and 15 were in BSN group with mean AS score of
      1.01 +/- 0.05. The mean AS was significantly different (P < 0.0001). AS of 1.06
      had sensitivity and specificity of 96.43% and 100% respectively (P = 0.0001).
      There was a trend of negative correlation between the AS and the duration, r = 
      0.21; however, it was not statistically significant (P = 0.28). CONCLUSION: TPBS
      should be considered in the evaluation of CRPS to rule out patients who have
      focal involvement, not diagnostic of CRPS (~24% in this study). Quantitative AS
      of 1.06 can be included to support visual interpretation in the delayed phase.

PMID- 24019669
TI  - Bremsstrahlung dose of therapeutic beta nuclides in bone and muscle.
AB  - In the nuclear medicine, beta nuclides are released during the treatment. This
      beta interacts with bone and muscle and produces external Bremsstrahlung (EB)
      radiation. Present work formulated a new method to evaluate the EB spectrum and
      hence the Bremsstrahlung dose of therapeutic beta nuclides (Lu-177, Sr-90, Sm
      153, I-153, Cs-137, Au-201, Dy-165, Mo-99, Sr-89, Fe-59, P-32, Ho-166, Sr-92, Re
      188, Y-90, Pr-147, Co-60, K-42) in bone and muscle. The Bremsstrahlung yields of
      these beta nuclides are also estimated. Bremsstrahlung production is higher in
      bone than that of muscle. Presented data provides a quick and convenient
      reference for radiation protection and it can be quickly employed to give a first
      pass dose estimate prior to a more detailed experimental study. 

PMID- 24019671
TI  - Dual ectopic thyroid in the presence of atrophic orthotopic thyroid gland in a
      patient with acquired hypothyroidism: Evaluation with hybrid Single-Photon
      Emission Computed Tomography/Computed Tomography.
AB  - Ectopic thyroid tissue (ETT) refers to all cases in which the thyroid gland is
      present at a location other than its usual site. The prevalence of ETT is
      approximately one per 100,000 to 300,000 persons and is reported to occur in one
      in 4,000 to 8,000 patients with thyroid disease. Multiple ectopia of thyroid is
      extremely rare. Multiple ectopia in the presence of orthotopic thyroid gland is
      extremely rare. We report a 13-year-old boy with stunted growth and developmental
      delay caused due to acquired hypothyroidism. Technetium scan performed as per
      management protocol identified dual ectopia of thyroid. The role of hybrid Single
      Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) in the
      localization of the sites of ETT is also highlighted. 

PMID- 24019670
TI  - Post meningitis subdural hygroma: Anatomical and functional evaluation with
      (99m)Tc-ehylene cysteine dimer single photon emission tomography/computed
      tomography.
AB  - Subdural hygroma is the collection of cerebrospinal fluid in the subdural space.
      Most often these resolve spontaneously. However, in cases with neurological
      complications surgical drainage may be needed. We here, present the case of an 8
      year-old boy with post meningitis subdural hygroma. (99m)Tc-ehylene cysteine
      dimer ((99m)Tc-ECD) hybrid single photon emission tomography/computed tomography
      (SPECT/CT) carried out in this patient, demonstrated the subdural hygroma as well
      as the associated cerebral hypoperfusion. If (99m)Tc-ECD SPECT/CT is integrated
      into management of these patients, it can help in decision making with respect to
      conservative versus surgical management. 

PMID- 24019672
TI  - Solitary sternal metastasis from hepatocellular carcinoma detected by F-18 FDG
      PET/CT.
AB  - Fluorine-18 fluoro-deoxy-glucose positron emission tomography (F-18 FDG PET) is
      not sensitive modality for the diagnosis of primary hepatocellular carcinoma
      (HCC). However, FDG-PET imaging may be useful in the identification of
      extrahepatic metastases. We report an interesting image of HCC with solitary
      metastasis to sternum detected by F-18 FDG PET/CT. 

PMID- 24019673
TI  - Autoimmune pancreatitis: An incidental detection on FDG PET/CT with response to
      steroid therapy.
AB  - Autoimmune pancreatitis (AIP) is most often incidentally detected, with the
      diagnosis being based on radiological characteristics. A steroid regimen for 6
      weeks is the standard line of treatment for AIP. In our case, AIP was
      incidentally suspected on fluorodeoxyglucose positron emission
      tomography/computed tomography (PET/CT) performed for staging a malignancy, and a
      follow-up PET/CT study after steroid treatment, showed complete metabolic and
      morphological response; thus confirming the imaging diagnosis of AIP. 

PMID- 24019674
TI  - Left is right and right is wrong: Fluorodeoxyglucose uptake in left hemi
      diaphragm due to right phrenic nerve palsy.
AB  - A 36-year-old Indian man, a recently diagnosed case of the right lung carcinoma
      underwent fluorodeoxyglucose positron emission tomography-computed tomography
      (FDG PET/CT) for staging of the malignancy. PET/CT showed increased FDG uptake in
      the right lung mass, consistent with the known primary tumor. Right hemidiaphragm
      was found to be elevated on CT, suggesting right diaphragmatic paresis. The PET
      scan demonstrated asymmetric, intense FDG uptake in the left hemidiaphragm and
      accessory muscles of respiration, which was possibly due to compensatory
      increased workload related to contralateral right diaphragmatic paresis. The
      right diaphragmatic paresis was hypothesized to be caused by phrenic nerve palsy
      by right lung neoplasm. 

PMID- 24019675
TI  - Skeletal muscle metastases as the initial manifestation of an unknown primary
      lung cancer detected on F-18 fluorodeoxyglucose positron emission
      tomography/computed tomography.
AB  - Skeletal muscle metastasis as the initial presentation of the unknown primary
      lung cancer is unusual. A 65-year-old male patient presented with pain and
      swelling of the right forearm. Fine needle aspiration of the swelling revealed
      metastatic squamous cell carcinoma. The patient underwent whole body F-18
      fluorodeoxyglucose (FDG) positron emission tomography/computed tomography
      (PET/CT) to identify the site of the primary malignancy. The authors present
      PET/CT images showing FDG-avid metastases to the skeletal muscles along with a
      previously unknown primary tumor in the right lung, in a patient presenting with
      initial muscular symptoms without any pulmonary manifestations. 

PMID- 24019676
TI  - F18 FDG positron emission tomography revelation of primary testicular lymphoma
      with concurrent multiple extra nodal involvement.
AB  - Primary testicular lymphoma (PTL) a relatively rare disease of non-Hodgkin's
      lymphomas occurring with a lesser incidence of 1-2% has a propensity to occur at
      later ages above 50 years. PTL spreads to extra nodal sites due to deficiency of
      extra cellular adhesion molecules. We present detection of multiple sites of
      extra nodal involvement of PTL by F-18 positron emission tomography/computed
      tomography study aiding early detection of the dissemination thus aiding in
      staging and management. 

PMID- 24019678
TI  - Radionuclide cisternography: A prudent investigation in diagnosing spontaneous
      intracranial hypotension.
AB  - Spontaneous intracranial hypotension (SIH) is a cause of new persistent headache,
      which disappears on recumbence and reappears in sitting/standing position
      (orthostatic headache). We present a case of orthostatic headache, where the
      patient was suspected to have SIH and was subjected to radionuclide
      cisternography (RNC) using 99m Technetium Diethylenetriaminepenta acetic acid for
      confirmation of diagnosis. After due consent from the patient, the radiotracer
      was injected intra-thecally and serial images were acquired until 24 h. The
      direct and indirect evidences of Cerebrospinal fluid (CSF) leakage, which were
      revealed in our study, provided objective evidence to the clinical diagnosis. RNC
      is an important investigation in diagnosing SIH and also identifying the site of
      CSF leak, which may aid the management. 

PMID- 24019677
TI  - Dual tracer functional characterization of metastatic gastric carcinoid.
AB  - Because of the increasing clinical importance of gastric carcinoids and the
      difficulty in diagnosing them, the need for non-invasive diagnostic methods is
      growing. Currently, the only reliable method is upper gastrointestinal endoscopy
      with biopsy. We report the case of a 32-year-old male where a combination of
      functional imaging studies ((18)F-fluorodeoxyglucose-positron emission
      tomography/computed tomography [PET/CT] and (68)Ga-DOTA-NOC PET/CT) not only
      helped in the correct staging, but also highlighted certain important biological
      aspects of these tumors, which are important from the management point of view
      and can prognosticate the patients. 

PMID- 24019679
TI  - Enterogastroesophageal reflux detected on 99m-technetium sestamibi cardiac
      imaging as a cause of chest pain.
AB  - Myocardial perfusion imaging (MPI) with technetium-99m sestamibi (Tc-99m MIBI) is
      considered a diagnostic technique that is widely used for the investigation of
      suspected coronary artery disease. Incidental inspection of an extracardiac
      activity is indirect, but important marker, which can identify a potentially
      treatable non-coronary cause for chest pain that may mimic cardiac symptoms.
      Here, we present an illustrative case in which significant enterogastroesophageal
      reflux of Tc-99m MIBI occurred during the cardiac imaging following prompt
      hepatobiliary clearance. Because, there was normal myocardial perfusion on MPI,
      presence of gastroesophageal reflux (GER) on GER scintigraphy and detection of
      mild inflammation with pathologically confirmed hyperplastic polyp by endoscopy,
      in view of the above findings we concluded that the probable cause of chest pain
      was reflux. 

PMID- 24019680
TI  - Fluorodeoxyglucose positron emission tomography-computed tomography findings in a
      case of xanthogranulomatous pyelonephritis.
AB  - Xanthogranulomatous pyelonephritis (XGNP) is an uncommon condition characterized
      by chronic suppurative renal inflammation that leads to progressive parenchymal
      destruction. This condition can clinically present as recurrent urinary tract
      infections, flank pain, hematuria, and occasionally sepsis, and weight loss. This
      condition is usually associated with obstructing renal calculus. We present 18
      fluorodeoxyglucose positron emission tomography-computed tomography (18-FDG
      PET/CT) findings in an elderly male suffering from pyrexia and weight loss and
      suspected urinary tract infection. PET/CT findings in this case lead to diagnosis
      of XGNP. This diagnosis should be kept in mind while evaluating similar symptoms
      and PET/CT scan findings. 

PMID- 24019681
TI  - Ventilation/Perfusion scan aids in the diagnosis of diabetes mellitus induced
      trepopnea due to isolated right phrenic nerve palsy.
AB  - Dyspnea can rarely be due to diabetes mellitus induced neuropathy. The term
      "trepopnea' is sparingly used in clinical practice and refers to dyspnea on
      assuming a particular lateral decubitus position Trepopnea is rarely described in
      association with unilateral diaphragmatic paralysis, which in itself is an
      uncommon cause of respiratory distress. We report a 27-year-old diabetic female
      who presented with sudden onset of dyspnea. On close interrogation, patient
      complained of dyspnea that was exaggerated while lying on the left side (left
      lateral decubitus position). A fluoroscopic sniff test showed a paradoxically
      moving right diaphragm confirming the diagnosis of unilateral diaphragmatic
      paralysis attributed to diabetes induced isolated phrenic nerve palsy. This case
      highlights the importance of ventilation - perfusion imaging in non-pulmonary
      etiologies and also attaches importance in recognizing trepopnea as an early
      clinical symptom of diaphragmatic paralysis. This case illustrates that diabetic
      neuropathy due to isolated phrenic nerve palsy can occur in the absence of
      peripheral neuropathy and that glycemic control is unrelated to the manifestation
      or severity of this disease. 

PMID- 24019683
TI  - Diffuse lung uptake in stress myocardial perfusion scintigraphy with Thallium-201
      in a patient with sarcoidosis.

PMID- 24019682
TI  - Extensive tumor thrombus of hepatocellular carcinoma in the entire portal venous
      system detected on fluorodeoxyglucose positron emission tomography computed
      tomography.
AB  - Detection of thrombus is usually an incidental finding on fluorodeoxyglucose
      positron emission tomography/computed tomography studies. Nevertheless this is an
      important finding in terms of disease prognostication and in planning the
      treatment strategy. We herein report a case of a 50-years-old male, a diagnosed
      case of hepatocellular carcinoma with extensive hypermetabolic thrombus involving
      the entire portal venous system. 

PMID- 24019684
TI  - Increased flurodeoxyglucose uptake observed in the diaphragm and vocal cords on
      whole body 18F flurodeoxyglucose positron emission tomography with computerized
      tomography scan in a patient with uncontrolled hiccups of unknown origin.

PMID- 24019685
TI  - Usefulness of single photon emission computed tomography (SPECT)/computed
      tomography and radioguided surgery in a patient with recurrent pheochromocytoma.

PMID- 24019686
TI  - Does case selection and outcome following laparoscopic colorectal resection
      change after initial learning curve? Analysis of 235 consecutive elective
      laparoscopic colorectal resections.
AB  - INTRODUCTION: Laparoscopic colorectal surgery is being widely practiced with an
      excellent short-term and equal long-term results for colorectal diseases
      including cancer. However, it is widely believed that as the experience of the
      surgeon/unit improves the results get better. This study aims to assess the
      pattern of case selection and short-term results of laparoscopic colorectal
      surgery in a high volume centre in two different time frames. MATERIALS AND
      METHODS: This study was done from the prospective data of 265 elective
      laparoscopic colorectal resections performed in a single unit from December 2005
      to April 2011. The group was subdivided into initial 132 patients (Group 1) from
      December 2005 to December 2008 and next 133 patients (Group 2) between December
      2008 and April 2011 who underwent laparoscopic colorectal resections for cancer.
      The groups were compared for intraoperative and perioperative parameters, type of
      surgery, and the stage of the disease. RESULTS: The age of patients was similar
      in Groups 1 and 2 (57.7 and 56.9, respectively). Patients with co-morbid illness
      were significantly more in Group 2 than in Group 1 (63.2% vs. 32.5%,
      respectively, P<=0.001). There were significantly more cases of right colonic
      cancers in Group 1 than in Group 2 (21.9% vs. 11.3%, respectively, P<0.02) and
      less number of low rectal lesions (20.4% vs. 33.8%, respectively, P<=0.02). The
      conversion rates were 3.7% and 2.2% in Groups 1 and 2, respectively. The
      operating time and blood loss were significantly more in Group 1 than in Group 2.
      The ICU stay was significantly different in Groups 1 and 2 (31.2+/- 19.1 vs.
      24.7+/- 18.7 h, P<=0.005). The time for removal of the nasogastric tube was
      significantly earlier (P=0.005) in Group 2 compared to Group 1 (1.37+/- 1.1 vs.
      2.63+/-1.01 days). The time to pass first flatus, resumption of oral liquids,
      semisolid diet, and complications were similar in both groups. The hospital stay
      was more in Group 1 than in Group 2 ( P<=0.01). The numbers of lymph nodes
      retrieved was similar in both groups. The T stage of the disease in Groups 1 and
      2 were similar, however, the number of T4 lesions was significantly more in Group
      2 (8.3% vs. 18.7%, respectively, P<0.01). CONCLUSION: This study shows that with
      increasing experience, laparoscopic colorectal surgery can be practiced safely
      with minimal conversion rates and morbidity. As the units experience improves,
      there is a trend towards selecting advanced cases and performing complex
      laparoscopic colorectal procedures. With increasing experience, there is a trend
      towards better short-term outcome after laparoscopic colorectal surgeries.

PMID- 24019687
TI  - Transumbilical single-incision laparoscopic sleeve gastrectomy: Short-term
      results and technical considerations.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (SG) has gained popularity and
      acceptance among bariatric surgeons, mainly due its low morbidity and mortality.
      Single-incision laparoscopic surgery has emerged as another modality of carrying
      out the bariatric procedures. While the single-incision transumbilical (SITU)
      approach represents an advance, especially for cosmetic reasons, its application
      in morbid obesity at present is limited. We describe our short-term surgical
      results and technical considerations with SITU-SG. MATERIALS AND METHODS: SITU-SG
      was performed in 10 patients between June 2010 and June 2011. SG was performed in
      a standard fashion and was started 6 cm from the pylorus using a 36 French
      bougie. RESULTS: They were all females with a mean age of 45 years. Preoperative
      BMI was 40 kg/m(2) (range, 35-45). The mean operative time was 98 min. No peri-
      or postoperative complications or deaths occurred. All patients were very
      satisfied with the cosmetic outcomes and excess weight loss. CONCLUSION: True
      SITU laparoscopic SG is safe and feasible and can be performed without changing
      the existing principles of the procedure.

PMID- 24019688
TI  - Outcomes of Xanthogranulomatous cholecystitis in laparoscopic era: A
      retrospective Cohort study.
AB  - INTRODUCTION: Xanthogranulomatous cholecystitis (XGC) is a rare variant of
      cholecystitis and reported incidence of XGC varies from different geographic
      region from 0.7% -9%. Most of the clinicians are not aware of the pathology and
      less evidence is available regarding the optimal treatment of this less common
      form of cholecystitis in the present era of laparoscopic surgery. MATERIALS AND
      METHODS: A retrospective cohort study was conducted in a tertiary care university
      hospital from 1989 to 2009. Histopathologically confirmed XGC study patients
      (N=27) were compared with non-Xanthogranulomatous cholecystitis (NXGC) control
      group (N=27). The outcomes variables were operative time, complication rate and
      laparoscopic to open cholecystectomy conversion rate. The study group (XGC) was
      further divided in to three sub groups; group I open cholecystectomy (OC),
      laparoscopic cholecystectomy (LC) and laparoscopic converted to open
      cholecystectomy (LCO) for comparative analysis to identify the significant
      variables. RESULTS: During the study period 6878 underwent cholecystectomy
      including open cholecystectomy in 2309 and laparoscopic cholecystectomy in 4569
      patients. Histopathology confirmed xanthogranulomatous cholecystitis in 30
      patients (0.43% of all cholecystectomies) and 27 patients qualified for the
      inclusion criterion. Gallbladder carcinoma was reported in 100 patients (1.45%)
      during the study period and no association was found with XGC. The mean age of
      patients with XGC was 49.8 year (range: 29-79), with male to female ratio of 1:3.
      The most common clinical features were abdominal pain and tenderness in right
      hypochondrium. Biliary colic and acute cholecystitis were the most common
      preoperative diagnosis. Ultrasonogram was performed in all patients and CT scan
      abdomen in 5 patients. In study population (XGC), 10 were patients in group I, 8
      in group II and 9 in group III. Conversion rate from laparoscopy to open was 53 %
      (n=9), surgical site infection rate of 14.8% (n=4) and common bile duct injury
      occurred one patient in open cholecystectomy group (3.7%). Statistically
      significant differences between group I and group II were raised total leukocyte
      count: 10.6+/-3.05 vs. 7.05+/-1.8 (P-Value 0.02) and duration of surgery in
      minutes: 248.75+/-165 vs. 109+/-39.7 (P-Value 0.04). The differences between
      group III and group II were duration of surgery in minutes: 208.75+/-58 vs. 109+/
      39.7 (P-Value 0.03) and duration of symptoms in days: 3+/-1.8 vs. 9.8+/-8.8 (P
      Value 0.04). The mean hospital stay in group I was 9.7 days, group II 5.6 days
      and in group III 10.5 days. Two patients underwent extended cholecystectomy based
      on clinical suspicion of carcinoma. No mortality was observed in this study
      population. Duration of surgery was higher in XGC group as compared to controls
      (NXGC) (203+/-129 vs.128+/-4, p-value=0.008) and no statistically significant
      difference in incidence proportion of operative complication rate were observed
      among the group (25.9% vs. 14.8%, p-value=0.25. Laparoscopic surgery was
      introduced in 1994 and 17 patients underwent laparoscopic cholecystectomy and
      higher conversion rate from laparoscopic to open cholecystectomy was observed in
      17 study group (XGC) as compared to 27 Control group (NXGC) 53%vs.3.3% with P
      value of < 0.023. CONCLUSION: XGC is a rare entity of cholecystitis and
      preoperative diagnosis is a challenging task. Difficult dissection was
      encountered in open as well in laparoscopic cholecystectomy with increased
      operation time. Laparoscopic cholecystectomy was carried out with high conversion
      rate to improve the safety of procedure. Per operative clinical suspicion of
      malignancy was high but no association of XGC was found with gallbladder
      carcinoma, therefore frozen section is recommended before embarking on radical
      surgery.

PMID- 24019689
TI  - Gasless single incision trans-axillary thyroidectomy: The feasibility and safety
      of a hypo-morbid endoscopic thyroidectomy technique.
AB  - INTRODUCTION: A range of minimally invasive endoscopic techniques (gas dependent
      and gasless) have been attempted for thyroidectomy in the past two decades. In
      this context, we evaluated the feasibility and safety of our technique of a
      gasless trans-axillary thyroidectomy. MATERIAL AND METHODS: This retrospective
      study from the Department of Endocrine and metabolic surgery in Southern India
      included 15 cases. The details of operative technique, intra and postoperative
      data were documented in all the cases. Only cases with benign thyroid nodules
      were included. Exclusion criteria were diffuse toxic goiters (Graves' disease),
      thyroid cancer, > 6 cm nodules, recurrent goitres and patients with shoulder
      joint pathology. Statistical analysis was done with SPSS software 12.0 version.
      RESULTS: F:M -14:2. Mean age of the patient group was 26.4 years (15-52). Mean
      operative time was 123.4 (82-206) minutes. The only specific complications were
      induration in the infraclavicular area between axillary incision and thyroid
      region, prolonged wound drainage and stiffness in lower 3(rd) of
      sternocleidomastoid. Wound drainage lasted for 5.4 days (4 -8). There was no
      significant operative morbidity. CONCLUSION: This gasless trans-axillary
      technique for nodular goitres is safe and effective in the hands of an
      experienced thyroid surgeon.

PMID- 24019690
TI  - Two-port laparoscopic cholecystectomy with modified suture retraction of the
      fundus: A practical approach.
AB  - CONTEXT: Although transumbilical single incision laparoscopic cholecystectomy
      (SILC) has been demonstrated to be superior cosmetic, it is only limited to
      simple cases at present. In complex cases, the standard four- or three-port LC is
      still the treatment of choice. AIM: To summarize the clinical effect of a
      modified technique in two-port LC. SETTINGS AND DESIGN: A consecutive series of
      patients with benign gallbladder diseases admitted to the provincial teaching
      hospital who underwent LC in the past 4 years were included. A modified two-port
      LC was the first choice except for those requiring laparoscopic common bile duct
      exploration (LCBDE). MATERIALS AND METHODS: The operation was done with suture
      retraction of the fundus by a needle-like retractor. The patients' data,
      including the operative time, time consumed by gallbladder retraction, operative
      bleeding, conversion rate, rate of adding trocars, and postoperative
      complications were recorded. STATISTICAL ANALYSIS: Data were expressed as
      percentage and mean with standard deviation. RESULTS: Total 107 patients with
      chronic calculous cholecystitis (N = 61), acute calculous cholecystitis (N = 43),
      and cholecystic polyps (N = 3) received two-port LC. The procedure was successful
      in 99 out of 107 cases (success rate, 92.5%), and a third trocar was added in the
      remaining 8 cases (7.5%) due to severe pathological changes. The operative time
      was 47.2 (+/-13.21) min. There was no conversion to open surgery. CONCLUSION: Two
      port LC using a needle-like retractor for suture retraction of the gallbladder
      fundus is a practical approach when considering the safety, convenience, and
      indications as well as relatively minimal invasion.

PMID- 24019691
TI  - Primary posterior perineal herniation of urinary bladder.
AB  - Primary perineal hernia is a rare clinical condition wherein herniation of
      viscera occurs through pelvic diaphragm. They are usually mistaken for sciatic
      hernia, rectal prolapse or other diseases in the perineum. Correct identification
      of the type of hernia by imaging is crucial for planning treatment. We present a
      case of primary posterior herniation of urinary bladder and rectal wall through
      levator ani repaired laparoscopically using a mesh repair. 

PMID- 24019692
TI  - Laproendoscopic single site oesophageal diverticulectomy.
AB  - Epiphrenic divericula are uncommon disorders of the lower oesophagus, which are
      symptomatic in only 15-20% of cases. The optimum treatment modality for such
      cases remains an oesophageal diverticulectomy with long myotomy with or without
      an antireflux operation. Recently, this is increasingly being done through the
      laparoscopic approach. Here we describe the first reported case of oesophageal
      diverticulectomy through the laparoendoscopic single site approach. A 57-year-old
      man presented to us with 6 months history of dysphagia and regurgitation. Patient
      was investigated with upper gastrointestinal (UGI) endoscopy, barium swallow,
      CECT chest and abdomen, oesophageal manometry and 24 hour pH study. He was
      diagnosed to have lower oesophageal diverticulum with mildly elevated pressure
      readings in manometric studies with normal peristalsis. Based on his symptoms, he
      was taken up for surgery. A laparoscopic transhiatal oesophageal diverticulectomy
      with myotomy was done through laparoendoscopic single site technique. The
      procedure lasted 160 min. There was no intraoperative complication. Gastrograffin
      study was done on postoperative day 2 following which he was started on liquids.
      He made an uneventful recovery and was discharged on fourth day. He remained
      asymptomatic on follow up. Oesophageal diverticulectomy is possible through
      laparoendoscopic single site approach if necessary expertise is available. 

PMID- 24019693
TI  - Single incision laparoscopic distal pancreatectomy with splenectomy for
      neuroendocrine tumor of the tail of pancreas.
AB  - Laparoscopic resection is becoming the standard of care for tumors located in the
      body and tail of pancreas. We herein report a patient with neuroendocrine tumor
      in the tail of pancreas who underwent single incision laparoscopic distal
      pancreatectomy with splenectomy without the use of a commercial port device. 

PMID- 24019694
TI  - A case of complete transection of right main bronchus in a child: Role of
      thoracoscopy and bronchoscopy.
AB  - Isolated tracheobronchial injuries are extremely rare in children and challenging
      due to life threatening complications. Blunt trauma to chest, especially in
      pediatric age group, is usually associated with multi-organ involvement and high
      mortality rate. These patients rarely reach a hospital. We have described here a
      case of complete transection of right main bronchus in a child, without hilar
      vascular injury, and its successful management, emphasizing the role of
      bronchoscopy and thoracoscopy. 

PMID- 24019695
TI  - Erosion of small intestine with necrotising fasciitis of over lying abdominal
      wall after expanded poly-tetrafluoroethylene mesh implantation: A rare
      complication after laparoscopic incisional hernia repair.
AB  - Complications such as bowel erosions, enterocutaneous fistulae are rare with the
      use of expandedpoly-tetrafluoroethylene (ePTFE) mesh in laparoscopic incisional
      hernia repair (LIHR). This unusual case patient presented to us with necrotising
      fasciitis of overlying anterior abdominal wall with peritonitis withsepticaemia
      and underwent aLIHR6 weeks before, which has not been reported till yet. We
      report a case of LIHR, presented to us with necrotising fasciitis of overlying
      anterior abdominal wall, peritonitis and septicaemia which was managed by small
      bowel segmental resection and exteriorisation of the ends, debridement of
      overlying anterior abdominal wall and maximum resection of implanted mesh. This
      case is unusual secondary to long experience with ePTFE mesh and the lack of
      published cases similar to this one. A brief review of relevant literature has
      been included in the article. We recommend pre-peritoneal placement of dual mesh
      fixed preferably by trans-abdominal polypropylene suture in LIHR. 

PMID- 24019696
TI  - A simplified protocol of combined thoracoscopy and laparoscopic excision for
      large subdiaphragmatic hepatic hydatid cysts.
AB  - Human hydatid disease caused by echinococcus granulosus is one of the commonest
      zoonosis and it primarily affects the liver. Amongst, the various treatment
      options, surgical management with removal of its contents and pericystectomy
      under the cover of anti-helminthic is the treatment of choice. Large hydatid
      cysts located in the posterosuperior aspect of liver often require thoracic
      approach. In this context, we describe an innovative combined thoraco
      laparoscopic technique for the surgical treatment of large subdiaphragmatic
      hepatic hydatid cyst. 

PMID- 24019697
TI  - Laparoscopic vertical sleeve gastrectomy after open gastric banding in a patient
      with situs inversus totalis.

PMID- 24019698
TI  - Thoughts for the future.

PMID- 24019699
TI  - Antibodies against rickettsia in humans and potential vector ticks from Dhofar,
      Oman.
AB  - OBJECTIVE: To determine the extent of rickettsial infections prevalence of
      potential vector ticks in the rural population of Dhofar, Oman. METHOD: Human
      sera (n = 347) were obtained from six rural localities (school children, farmers,
      outpatients) in Dhofar, Sultanate of Oman. Sera were tested by immunofluorescence
      for the presence of antibodies reacting with Rickettsia conorii antigen. RESULTS:
      More than half the samples (59%) gave positive reactions (titres of at least
      1:64). Ticks (n=707) were collected from cattle, camels and goats (n=102) and
      included Amblyomma variegatum, Hyalomma a. anatolicum, H. dromedarii, H. rufipes
      and Rhipicephalus spp., all of which can potentially transmit rickettsiae to
      humans. CONCLUSION: The results suggest that rickettsial infections are common
      among the rural population of Dhofar.

PMID- 24019700
TI  - Effect of single mismatches at 3'-end of primers on polymerase chain reaction.
AB  - OBJECTIVE AND METHOD: To investigate the effect of three different mismatches
      (G/T, G/A or G/G) at the 3'-end of a primer to amplify a 268 bp (base pair)
      region of the human beta-globin gene using different annealing temperatures (45
      to 65 degrees C). RESULTS: The primer with the G/T mismatch was as efficient as
      the normal primer (G/C match) in the amplification of a 268 bp product at all
      temperatures tested. However, the primers having G/A or G/G mismatches at the 3'
      end did not produce any specific polymerase chain reaction (PCR) fragment at all
      the annealing temperatures used, except a barely detectable 268 bp product for
      the G/G mismatch at 45 and 50 degrees C. CONCLUSION: We conclude that our PCR
      system was refractory to amplification when one of the primers contained a G/A or
      G/G mismatch at the 3'-end with template DNA.

PMID- 24019701
TI  - Thymic proliferative response during different physiological states: a
      comparative study.
AB  - OBJECTIVE: To study the thymic proliferative response during different
      physiological states to distinguish those changes due to alterations in steroid
      hormone secretion from those resulting from the presence of spermatozoa and/or
      early conceptual products in the female reproductive tract. METHOD: Using mature
      female rats of an inbred AO(RT1(u)) strain, observations on the thymus were made
      at 24 hour intervals during the oestrous cycle, early pseudopregnancy and early
      syngeneic pregnancy. Each daily group contained a minimum of 6 animals. RESULTS:
      During the oestrous cycle, a significant mid-cycle increase of thymocyte
      proliferation occurred during dioestrus which peaked on day 2, and as a
      repetitive response may be a preparation for a coital challenge. This response
      may be oestrogen-dependent since oestrogen levels begin to increase during early
      dioestrus. The induction of pseudopregnancy generates a comparable but delayed
      increase in thymic proliferative activity. Since thymocyte proliferation and
      oestrogen secretion both peak on day 3 of pseudopregnancy, such a response may
      indeed also be oestrogen-dependent. After syngeneic mating, there was a
      significant depression in thymic proliferative activity on day 3 followed by a
      significant increase on day 5 compared with the same days of pseudopregnancy.
      CONCLUSION: This initial depression of proliferative activity may be induced by
      the immunosuppressive action of seminal plasma, to safeguard the preimplantation
      conceptus while the day 5 increase in cellular proliferation suggests a response
      to implantation.

PMID- 24019702
TI  - In-vitro activity of synercid and related drugs against Streptococcus oralis
      isolated from septicaemia and endocarditis cases.
AB  - OBJECTIVE: The increase in resistance to gram positive organisms and seriousness
      of infective endocarditis, makes it necessary to look for an alternate treatment.
      METHOD: In-vitro activity of synercid was compared with penicillin, amoxycillin,
      teicoplanin, vancomycin, clindamycin and erythromycin. RESULT: Synercid showed
      minimum inhibitory concentrations (MIC) within the narrow range of 0.06 - 0.5
      mg/l. MIC50 and mode values were both 0.25 mg/l. There was just two-fold
      difference between the MIC50 (0.25 mg/l) and the MIC90, (0.5 mg/l). Although the
      MICs of synercid for S. oralis were relatively high compared to penicillin,
      clindamycin, erythromycin and teicoplanin, the in-vitro bactericidal activity of
      synercid was much greater. Synercid MBC values were < 4 mg/l for most of the
      isolates, except for one of 16 mg/l and the other >64 mg/l. Killing curve was
      performed on six isolates of S. oralis from infective endocarditis, two from
      septicaemia patients and two from the oral flora of normal individuals.
      CONCLUSION: Synercid showed superior bactericidal activity when compared to
      penicillin and vancomycin against all ten isolates of S. oralis tested. Synercid
      was bactericidal (99.9% kill) against all ten isolates of S. oralis within six
      hours of contact.

PMID- 24019703
TI  - Minimal stimulation protocol: a cheap and effective method of ovulation
      induction.
AB  - OBJECTIVE: To determine the effectiveness and cost of Minimal Stimulation
      Protocol (MSP), a new combination of human menopausal gonadotrophin (hMG) and
      clomiphene citrate (CC), for controlled ovarian hyperstimulation. METHOD: The
      ovulation rates, pregnancy rates, abortion rates and the cost of medication were
      assessed in respect of 67 women who underwent MSP. RESULTS: Ovulation rate in the
      study group was 82%, pregnancy rate 21% and multiple pregnancies 7%. Spontaneous
      abortion occurred in 36% of the pregnancies. The average cost of MSP stimulation
      was one-third of hMG protocol. CONCLUSION: MSP protocol, while substantially
      cheaper than hMG, gives comparable pregnancy rates with less need for monitoring
      and better patient comfort. These justify further evaluation of its role in the
      treatment of infertility.

PMID- 24019704
TI  - Physical fitness and fatness among Omani schoolboys: a pilot study.
AB  - OBJECTIVE: To study the applicability of simple field measurements of physical
      fitness in a sample of Omani boys and their relationships to selected variables.
      METHOD: Two field measures of physical fitness-the time to complete 1.6-km
      run/walk and the sum of 5 skinfold thicknesses-were correlated with personal and
      family physical activity-related and other variables in a sample of 109 Omani
      boys aged 9-11 years. RESULTS: Obesity in parents, especially in the mother,
      showed significant correlation with both fitness measures. The waist/buttocks
      ratio showed no significant correlation with the 1.6-km time. The number of
      siblings and siblings sharing a room, number of T.V-watching hours and the number
      of servants in the family showed no correlation with the chosen fitness indices.
      CONCLUSION: The results of this pilot study indicate that simple field fitness
      tests can be used in children and they can yield valuable information related to
      physical fitness. The same protocol used in this study could be applied to a
      national study in Oman.

PMID- 24019705
TI  - Psychiatric morbidity in Northern Jordan: a ten-year review.
AB  - OBJECTIVE: To study the psychiatric morbidity in the northern part of Jordan and
      to determine the frequency distribution of various psychiatric disorders, for
      planning services. METHOD: All records of 2,335 psychiatric patients attending
      the only psychiatric clinic in Northern part of Jordan during a ten-year period
      from 1984 to 1993 were extensively reviewed and subjected to computerized
      analysis. Diagnosis was made as per ICD-9. RESULTS: Out of the 2335 patients who
      attended the clinic, 55% were males and 45% were females. Those in the age group
      25-44 recorded the maximum attendance. Among the male attendees of the clinic,
      schizophrenia was the commonest diagnosis(19.9%), while among females, affective
      disorders were the commonest(15.9%). CONCLUSION: Schizophrenia was found to be
      the commonest diagnosis in general among attendance of the clinic for the ten
      year research period, while anxiety disorders were the commonest diagnosis among
      attendance of the clinic for the year 1993.

PMID- 24019706
TI  - Laparoscopic surgery at Sultan Qaboos University Hospital.
AB  - Laparoscopic surgery, which gained prominence in the late 1980s, became an
      established surgical practice in Sultan Qaboos University Hospital (SQUH) in
      1992. Drawing on available literature and the authors' own experiences, this
      paper gives an overview of various laparoscopic surgical techniques currently
      available at SQUH, including laparoscopic cholecystectomy, laparoscopic
      appendicectomy, diagnostic laparoscopy and laparoscopic varicocoelectomy. It also
      highlights the role of surgical endoscopic training centre at SQUH, which
      provides a laboratory setting for surgical trainees and practising physicians.
      Laparoscopic surgery at SQUH would continue to evolve spurred on by surgical
      innovations and advances in technology. 

PMID- 24019707
TI  - Unilateral uterine artery embolization and systemic methotrexate therapy in
      cervical pregnancy.
AB  - The authors report a case of cervical pregnancy successfully treated with
      combined methods of uterine artery embolization and systemic methotrexate
      therapy. Unilateral selective embolization may play a role in preserving
      reproductive functions. 

PMID- 24019708
TI  - Supraventricular tachycardia in children: a report of three cases, diagnosis and
      current management.
AB  - The article presents three Omani children with supraventricular tachycardia and
      discusses the diagnosis and management. Clinical features along with ECG help
      diagnosis of this common paediatric arrhythmia. Acute management has been
      facilitated with the introduction of adenosine. However, longterm management
      continues to be a topic for debate. 

PMID- 24019709
TI  - Revamping neurorehabilitation in Oman.

PMID- 24019710
TI  - Usefulness of Kato-Katz and trichrome staining as diagnostic methods for
      parasitic infections in clinical laboratories.
AB  - OBJECTIVES: To assess the efficacy of the Kato-Katz technique and to re-evaluate
      other routine procedures conducted in the Microbiology Clinical Laboratory at
      Sultan Qaboos University Hospital (SQUH) and to throw light on the prevalence of
      intestinal parasitic infections among a small group of food handlers in Muscat.
      METHOD: Faecal samples collected from food handlers were examined using five
      parasitological techniques. RESULTS: Out of 100 faecal samples, 53 were positive
      for one or more of 11 intestinal parasites. The Kato-Katz and trichrome stain
      methods were found superior to the other techniques in detecting helminthic and
      protozoan infections, respectively. The auramine stain was useful only in
      detecting Cryptosporidium parvum oocysts. CONCLUSION: A combination of trichrome
      stain and Kato-Katz techniques for stool examination is sufficient and
      recommended for busy laboratories; auramine stain should be applied only to
      samples with suspected cryptosporidal infections.

PMID- 24019711
TI  - Can pharmacists influence the health-related quality of life of patients with
      asthma?: The New Zealand Pharmaceutical Care experience.
AB  - BACKGROUND: The newly emerging practice of Pharmaceutical Care requires that
      pharmacists take responsibility for the outcomes of drug therapy. Improvement in
      Quality of Life (QoL) represents the final outcome of the care process and
      indicates the success of interventions. OBJECTIVES: To assess the impact of a
      Pharmaceutical Care specialist asthma service provided by community pharmacists
      to a sample of patients with asthma, the outcome indicators being changes in
      health status and QoL. METHOD: Sixty-two adult asthma patients (17 years and
      older) living in two rural regions of New Zealand, were segregated into two
      groups for phased introduction to the service. The patients acted as their own
      controls before they received the pharmacists' service. They had been diagnosed
      with asthma at least six months previously, and their asthma was symptomatic and
      not considered optimally controlled prior to the study. RESULTS: There was
      significant improvement in asthma-related QoL (as measured by the Asthma Quality
      of Life Questionnaire) following introduction of the service, and pharmacists
      were able to identify, prevent or resolve over 400 drug-related problems.
      CONCLUSION: The results suggest that with appropriate training and support, New
      Zealand pharmacists can help asthma patients achieve greater quality of life.
      This research has implications for the introduction of Pharmaceutical Care
      services in other countries and for patients with other conditions who require
      ongoing management.

PMID- 24019712
TI  - Assessment of aerobic fitness and its correlates in Omani adolescents using the
      20-metre shuttle run test: A pilot study.
AB  - OBJECTIVE: To assess aerobic fitness in male and female adolescents using the
      multistage 20-metre shuttle run test and correlate it with selected fitness
      variables. METHOD: The subjects comprised 83 girls and 64 boys aged 15-16 years,
      randomly selected from two segregated government schools in Muscat. After the
      pupils filled in a short questionnaire on their personal leisure time activities
      of the preceding week, their heights and weights were measured. Aerobic fitness
      was assessed by estimating each pupil's minimal oxygen uptake levels (VO2max)
      using the multistage 20-metre shuttle running test (20-MST). RESULTS: Boys spent
      more time than girls on leisure physical activities, television, computer and
      video games and the Internet. The estimated VO2max in both boys and girls showed
      high correlation with their weekly physical activities. The time spent on
      television and computer negatively correlated with VO2max in girls but not in
      boys. Girls had higher body mass index (BMI) and less VO2max compared to boys;
      BMI showed a negative correlation with VO2max in girls but not in boys.
      CONCLUSION: Aerobic fitness in this sample was higher in boys than in girls and
      was strongly influenced by weekly physical activities in both genders. The 20-MST
      has proved a simple and inexpensive field test for aerobic fitness that could be
      implemented on a wide scale.

PMID- 24019713
TI  - Exaggerated blood pressure reactivity in the offspring of first-cousin
      hypertensive parents.
AB  - OBJECTIVE: To study blood pressure and blood pressure reactivity in young
      offspring of normotensive or hypertensive parents who are consanguineous (first
      cousins) or are not blood-related. METHOD: Blood pressure, heart rate and body
      mass index (BMI) were measured in 9-10 year-old male offspring of 19 pairs of
      first-cousins normotensive, 16 pairs of first-cousin hypertensive and 12 pairs of
      non-blood-related hypertensive parents. RESULTS: The offspring of first-cousin
      hypertensive parents exhibited the greatest systolic and diastolic blood pressure
      reactivity to their first casual blood pressure measurement, while the offspring
      of first-cousin normotensive parents showed the least reactivity. The offspring
      of the hypertensive parents who were not blood-related showed an intermediate
      reactivity. Basal systolic blood pressure (SBP) was also highest in the offspring
      of first-cousin hypertensive parents, and their basal diastolic blood pressure
      (DBP) was higher than that in offspring of first-cousin normotensive parents.
      CONCLUSION: The augmented blood pressure response in the offspring of
      hypertensive parents may have prognostic implications and serve as an important
      and significant indicator of predisposition to hypertension later in life.

PMID- 24019714
TI  - Vipassana meditation:: A naturalistic, preliminary observation in Muscat.
AB  - OBJECTIVES: To assess the effects of Vipassana meditation on the physical and
      psychological health in a multi-ethnic population in the city of Muscat. METHOD:
      The subjects were participants of a Vipassana meditation course taught in a ten
      day residential retreat. Self-assessments of health-related parameters and
      physical and psychological symptomatology were collected from them before and
      immediately after the course. A control group was tested for a similar time
      interval. RESULTS: Immediately after their 10-day training, the Vipassana
      participants assessed themselves significantly higher compared to their levels
      prior to the course, suggesting that the 10 days' practice had significantly
      improved their physical and psychological well-being. The control group did not
      exhibit such changes. CONCLUSION: The present preliminary findings, juxtaposed
      with the results of studies from other parts of the world, suggest that the
      practice of Vipassana meditation may help mitigate psychological and
      psychosomatic distress.

PMID- 24019716
TI  - Evidence-based Medicine:: An overview.
AB  - Evidence-based Medicine (EBM) has been proposed as the most significant
      intellectual advance in the process of clinical decision-making in the past
      decade. With more than 25,000 medical journals publishing 4 million articles a
      year, doctors are unable to cope with the information overload. The principles
      and practice of EBM show the way to bridge the gap between research and practice.
      Reactions evoked in the medical profession towards this new discipline have been
      in extremes, from outright rejection to enthusiastic acceptance. The goal of this
      paper is to familiarise the readers with the ideas and concepts associated with
      the phrase Evidence-based Medicine. 

PMID- 24019717
TI  - Thyrotoxicosis in pregnancy:: A case report.
AB  - There are various causes of hyperthyroidism in pregnancy such as Graves' disease
      and gestational thyrotoxicosis. The thyroid stimulation results from the
      excessive levels of circulating human chorionic gonadotropin (hCG) produced by
      the trophoblastic tissue in both hydatidiform moles and choriocarcinoma. We
      present a pregnant patient with hydatidiform mole who presented with
      hyperthyroidism that resolved after evacuation of the mole. 

PMID- 24019715
TI  - Neuropharmacology of dopamine receptors:: Implications in neuropsychiatric
      diseases.
AB  - There has been an extraordinary recent accumulation of information concerning the
      neurobiology and neuropharmacology of dopamine (DA) receptors in the mammalian
      central nervous system. Many new DA molecular entities have been cloned, their
      gene, peptide sequences and structures have been identified, their anatomical
      distributions in the mammalian brain described, and their pharmacology
      characterized. Progress has been made toward developing selective ligands and
      drug-candidates for different DA receptors. The new discoveries have greatly
      stimulated preclinical and clinical studies to explore the neuropharmacology of
      DA receptors and their implications in the neuropathophysiology of different
      neuropsychiatric diseases including schizophrenia, Parkinson's disease and
      attention-deficit hyperactivity disorder. Accordingly, it seems timely to review
      the salient aspects of this specialized area of preclinical neuropharmacology and
      its relevance to clinical neuropsychiatry. 

PMID- 24019718
TI  - Foreign bodies in the upper aero-digestive tract.
AB  - Foreign bodies in the upper aero-digestive tract pose major challenges to the
      otolaryngologist in both diagnosis and management. Aspirated and ingested foreign
      bodies are often emergencies, leading to inadequate study and poorly prepared,
      improper attempts at removal. The authors share their experience in managing
      upper aero-digestive tract foreign bodies in Omani population at a district
      hospital, present a statistical review of 58 cases, and highlight certain
      critical scenarios as well as cultural variations specific to the region. 

PMID- 24019719
TI  - Enemy within?: The silent epidemic of substance dependency in GCC countries.

PMID- 24019720
TI  - Effect of pegylated interferon on non-responders and relapsers with interferon.
AB  - OBJECTIVES: To assess whether a combination of pegylated interferon (interferon
      conjugated with polyethylene glycol) and ribavirin can improve the response rate
      in patients with chronic hepatitis C who either did not respond to (Non
      responders), or had relapsed after responding to (Relapsers) standard interferon
      and ribavirin combination therapy. PATIENTS AND METHODS: In this prospective
      study, 20 chronic hepatitis C patients (comprising 16 Non-responders and 4
      Relapsers to previous treatment with alpha interferon and ribavirin), were
      treated with pegylated interferon-2b weekly and ribavirin daily for one year.
      Eleven patients had genotype 4, eight were of genotype 1 and one patient had
      genotype 3. Response to treatment was determined based on normalisation of liver
      enzymes and negative viral load (assessed using qualitative HCV RNA PCR) at end
      of treatment (ETR) and 6 months off treatment (SVR). RESULTS: Seven patients
      (35%) achieved normalisation of liver enzymes and negative viral load at the end
      of treatment. However, only 2 patients (10%) managed to retain these levels after
      six months off treatment. The latter two patients had been previous Relapsers.
      CONCLUSION: Combination of pegylated interferon and ribavirin may be beneficial
      in previous relapsers with standard interferon-ribavirin combination therapy, but
      is unlikely to achieve sustained virological response in non-responders.

PMID- 24019721
TI  - Atopy in Omani patients with asthma.
AB  - OBJECTIVES: To determine the range of serum IgE in healthy subjects and in
      asthmatic patients in Oman and to assess the degree of atopy in the asthmatic
      patients. METHOD: Serum IgE and in vivo (the skin prick test) and in vitro (the
      ImmunoCAP test) allergen-specific IgE levels were measured in 44 patients with
      asthma. Control groups were 19 healthy subjects and 27 asymptomatic allergic
      subjects. RESULTS: The normal range for serum IgE in the Omani population was
      established at >= 101 IU/ml. The geometric mean (and 95% confidence interval) for
      asthmatic patients was 468 IU/ml (323-676). Positive results for allergen
      specific IgE, defined as responses to >= 1 allergen mix in the ImmunoCAP and to
      >= 3 allergens in the skin prick test, occurred in 26/35 (74%) and in 34/44(77%)
      asthmatic patients respectively. Six out of 38 patients with serum IgE >= 101
      IU/ml and 2/6 with levels <101 IU/ml gave negative and positive results
      respectively in the skin prick test. Overall, the degree of reactivity in the
      skin prick test correlated with the level of total serum IgE (r= 0.54, p<0.001).
      A similar correlation could not be established with ImmunoCAP reactivity, but
      sIgE levels >= 101 IU/ml were supported by a high frequency of positive ImmunoCAP
      responses for the majority of allergen mixes. CONCLUSIONS: Total serum IgE levels
      should be routinely monitored in asthmatic subjects as this may give an
      indication of atopy where skin prick testing is not indicated. Since in a
      minority of patients serum IgE levels and skin prick results do not predict in
      the same direction, all laboratory data should be interpreted in context of
      clinical history.

PMID- 24019722
TI  - Genotypes and allele frequencies of angiotensin converting enzyme (ACE)
      insertion/deletion polymorphism among Omanis.
AB  - OBJECTIVE: To describe the angiotensin converting enzyme (ACE) genotype
      frequencies among Omani Arabs. METHOD: A polymerase chain reaction (PCR) test,
      based on separation of different size DNA fragments, was developed to test the
      presence or absence (polymorphism) of a small DNA deletion in the ACE gene. The
      subjects were 124 Omani Arab students of Sultan Qaboos University, Muscat.
      RESULTS: The frequency of the I allele was 0.29, while that of the D allele was
      0.71. The gene frequency distribution did not deviate from Hardy-Weinberg
      equilibrium. CONCLUSIONS: The frequency of D allele among Omanis is similar to
      that among other Arabs and Africans, but differs significantly from that among
      the Japanese and Chinese.

PMID- 24019723
TI  - Caesarean sections at Sultan Qaboos University Hospital: A three year review.
AB  - OBJECTIVE: To review the caesarean sections (C/S) performed at Sultan Qaboos
      University Hospital (SQUH), Muscat, Oman, over a period of three years. METHOD:
      The records of 727 patients who underwent C/S at SQUH during the three year
      period from 1st July 1998 to 30th June 2001 were analysed. RESULTS: The C/S rate
      during this period was 13%, 42.6% of which were repeat C/S. Most were performed
      on women in the age group 26-30 years and of parity 2-3. The majority of the
      caesareans were at term and done under general anaesthesia. The most common
      indication was fetal distress and the most common complication was fever.
      CONCLUSION: The rate, indications, nature and frequency of complications of C/S
      performed at SQUH are similar to those at obstetric departments in academic
      hospitals in developed countries.

PMID- 24019724
TI  - Fluctuating antibody response in a cohort of hepatitis C patients.
AB  - OBJECTIVE: This project was designed to longitudinally study persons who had
      antibodies to hepatitis C virus (HCV) to characterise the serologic course of
      infection. METHODS: The subjects were 149 multitransfused patients (141 with
      thalassaemia major, 3 with thalassaemia intermedia, and 5 with sickle cell
      anaemia) who had been regularly followed up for 3 to 7 years. Sequential serum
      samples obtained semi-annually between January 1994 and January 2001 were tested,
      prospectively, by second or third generation HCV enzyme-linked immunosorbent
      assay (ELISA), followed by confirmatory recombinant immunoblot assay (RIBA-2 or
      RIBA-3). RESULTS: Of the 149 patients, 90 did not seroconvert to HCV, whereas 59
      had detectable antibodies. On the basis of RIBA results in these 59 patients, 24
      (41%) had persistent high antibody levels to structural and non structural HCV
      antigens, 11 (19%) had persistent low antibody levels, 17 (29%) showed
      fluctuating antibody levels, and in 5 patients (8%) there was a total or a
      partial disappearance of specific antibodies (seroreversion), mainly anti-core
      antibodies. Two patients (3%) had antibody responses that did not fit into any of
      these four categories. In patients with fluctuating antibody levels, there were
      periods ranging from 6 months to 2 years when anti-HCV antibodies could not be
      detected. CONCLUSION: This study shows that the antibody response to HCV in
      patients who receive frequent blood transfusions is very variable. Individuals
      who exhibit intermittent seropositivity are a challenge to diagnosis.

PMID- 24019725
TI  - Compliance of spectacle wear and its determinants among schoolchildren of
      Dhakhiliya region of Oman: A descriptive study.
AB  - OBJECTIVE: To determine the degree of compliance of spectacle wear and some of
      its determinants among school children of Dhakhiliya region of Oman. METHODS:
      This was a cross-sectional descriptive study of a sample of 663 students who had
      been prescribed spectacles for constant wear. After one year, experienced field
      staff conducted a follow-up visit where 571 of these students were examined.
      Information on age, gender, type and severity of refractive error was collected
      from the school health records and refractionist's report and analyzed to
      associate them to the compliance of spectacle wear. RESULTS: The majority (71.6%)
      of students were using spectacles at the time of follow up. The compliance rate
      was 65.1% in boys and 78.3% in girls. Agewise, it was 66.7% in 6-7-year-olds,
      66.7% in 12-13-year-olds and 79.1% in 16-17-year olds. The rate was 72.5% among
      students with myopia and 67.9% among those with hypermetropia. The compliance of
      spectacle wear was significantly higher among students with myopic refractive
      error of 2.5 D or more compared to those with less than 2.5 D. The difference in
      the compliance rates among students with hypermetropia of different grades was
      not significant. CONCLUSIONS: The study identifies the factors of high-risk of
      non compliance as (a) male gender, (b) younger age, and (c) low myopic refractory
      error. The eye health care program of Oman should focus on these high risk groups
      to further improve the compliance for visual aids.

PMID- 24019726
TI  - Visceral leishmaniasis and haemophagocytic syndrome in an Omani child.
AB  - The paper reports the case of a previously healthy 4-year-old-girl who presented
      with pallor, fever and hepatosplenomegaly. Laboratory findings included
      pancytopenia, hypertriglyceridemia and hyperferritinemia. Initial diagnosis of
      kala-azar could not be confirmed because of the absence of clinical evidence,
      negativity of bone marrow aspiration or specific serology for visceral
      leishmaniasis. Repeated marrow aspiration, performed due lack of clinical
      response, revealed histiocytes showing haemophagocytosis consistent with
      haemophagocytic lymphohistocytosis (HLH) and appropriate treatment was started.
      She continued to have high-grade fever, and a third bone marrow aspiration
      ultimately revealed presence of Leishmania amastigotes with evidence of active
      haemophagocytosis. The girl was treated with liposomal amphotericin (AmBisome)
      for 5 days, following which she recovered rapidly with definitive remission. 

PMID- 24019727
TI  - Epidemic infections and their relevance to the Gulf and other Arabian Peninsula
      countries.

PMID- 24019728
TI  - Screening for gestational diabetes by measuring fasting plasma glucose levels.
AB  - OBJECTIVES: (a) To test the sensitivity and specificity of measuring fasting
      plasma glucose levels (FPG) as a screening test for gestational diabetes mellitus
      (GDM). (b) To compare predicting levels of FPG levels with the one-hour, oral 50g
      non-fasting glucose challenge test (GCT) for predicting GDM. METHODS: One
      thousand and six hundred pregnant women from the Health Centres, antenatal
      clinics and Salmaniya Medical Complex were screened by the GCT after 50g of oral
      glucose during 26-32 weeks gestation, giving a 13.5% incidence of GDM (using the
      Third International Workshop cutoff values of 7.8 mmol /l). All patients also had
      an FPG estimation followed by the three-hour oral glucose tolerance test (oGTT).
      Seventy eight percent of the patients were Bahraini, 19% Asian and 3% other
      nationalities. Their mean age was 27.2+0.2 years. Receiver-operating curves (ROC)
      were used to test the ability of the FPG and the oGTT to differentiate patients
      with GDM and identify the cut off values for predicting a diagnosis of GDM.
      RESULTS: FPG levels of 5.6 mmol /l and 5.4 mmol /l yielded sensitivities and
      specificities of 94% and 93% respectively. Measuring FPG as a screening test
      required a diagnostic oGTT in 32% compared with 13% when the GCT was used.
      CONCLUSION: Using FPG levels at a cutoff value of >= 5.5 mmol /l is an easier,
      more acceptable test for patients compared to the GCT. Using the FPG levels is
      also more cost effective and allows nearly 70% of women to avoid the oGTT.

PMID- 24019729
TI  - Distribution of arylamine N-acetyltransferase 2 (nat2) genotypes among Omanis.
AB  - OBJECTIVE: to determine the genotypes of arylamine N-acetyltransferase (NAT2)
      among 127 unrelated apparently healthy Omanis. METHOD: Identify the most common
      known polymorphisms of NAT*2 gene namely, G(191)A, C(282)T, C(341)T, C(481)T,
      G(590)A, A(803)G and G(857)A using PCR-RFLP analysis. RESULTS: Eleven allele
      variants (3 alternative) and 30 different genotypes were determined. The
      commonest alleles were found to be NAT*5B, NAT2*6A and NAT*4 with corresponding
      frequencies of 0.362, 0.248 and 0.189 respectively. The overall frequency of
      rapid acetylator alleles was 0.25. CONCLUSION: A new allele variant containing
      G(590)A, C(282)T and T(341)C polymorphisms was found in one subject (was named
      NAT2*5J). The commonest genotypes were found to be 5B/5B, 5B/6A, 4/5B, 4/6A with
      frequencies 0.165, 0.157, 0.118, 0.110 and 0.079 respectively.

PMID- 24019730
TI  - Laboratory diagnosis of viral hepatitis C: The Sultan Qaboos University Hospital
      experience.
AB  - OBJECTIVES: A retrospective study was carried out to assess the performance of
      hepatitis C diagnostic assays in our laboratory, and to determine the prevalence
      of hepatitis C among blood donors at the Sultan Qaboos University Hospital.
      METHODS: From 1991 to 2001, approximately 55,000 serum samples collected from
      blood donors and patients were submitted to our laboratory for testing. All sera
      were screened for antibodies to hepatitis C virus (HCV) by three successive
      generations of the enzyme-linked immunosorbent assay (ELISA). Anti-HCV positive
      sera were further tested by recombinant immunoblot assay (RIBA). Reverse
      transcriptase polymerase chain reaction (RT-PCR) for HCV RNA was carried out on a
      limited number (241) of ELISA positive samples. RESULTS: Out of 30012 samples
      from blood donors that were screened for anti-HCV, 272 (0.91%) were positive. Of
      these, 46.5% were confirmed positive by RIBA. The proportion of patient sera that
      were confirmed positive varied from 95% among intravenous drug users to 81% in
      patients with hepatitis to 70% in those with haemoglobinopathies. HCV RNA was
      detected in 67%, 6%, and 0% of the RIBA positive, indeterminate and negative
      samples respectively. CONCLUSIONS: Based on RIBA, the prevalence of anti-HCV
      among blood donors in Oman is close to 0.5%. In our experience, RIBA-positivity
      is predictive of HCV infection in two thirds of subjects, and HCV infection is
      highly unlikely in those who are RIBA-negative. The experience at SQUH with three
      types of HCV assays has enabled the laboratory to develop a test algorithm,
      starting with screening anti-HCV ELISA.

PMID- 24019731
TI  - Magnitude and determinants of exodontia in South Batinah region of Oman: A cross
      sectional study.
AB  - OBJECTIVES: To estimate the magnitude, determinants and causes of exodontia
      presented at all the three dental units of South Batinah region of Oman. METHODS:
      This is a cross sectional study of 8,963 samples representing dental cases
      reported at the three dental units for 12 weeks in year 2000. The information on
      patients undergoing exodontia and its indications were collected from their case
      files. Standard definitions were used to categorise causes of exodontia. Mid 2000
      population was used as reference for calculating rates. Age-sex standardisation
      and 95% confidence interval of the exodontia rates were calculated for
      statistical validation. RESULTS: The annual exodontia rate was 16.67 per 1,000
      population (CI95% 16.52, 16.82). The rate in males was 11.56 (CI95% 11.40, 11.73)
      and and in females, 40.04 (CI95% 39.73, 40.34). The rate in the 12+ age group was
      significantly higher than that in the 0-12 age group. The rates showed geographic
      differences. CONCLUSIONS: The exodontia rates were high in the study area.
      Exodontia rates were significantly higher in females, persons older than 12
      years, and those living in the coastal areas of South Batinah. Based on the
      exodontia rates, the impact on the oral health services was reviewed and
      recommendations for improving the dental care were proposed.

PMID- 24019732
TI  - Radiology resident selection: Objective Restructured Interview to assess five
      essential attributes.
AB  - Like in other medical fields, candidates seeking a career in Radiology requires
      special skills and aptitudes. Selecting candidates for radiology residency is
      made difficult by the fact that many of the essential qualities predictive of a
      good radiology consultant, such as interpersonal skills, recognition of limits,
      curiosity, conscientiousness, and confidence level, are "non-cognitive", and thus
      difficult to assess. This paper describes the selection procedure developed by
      the Department of Radiology of Baylor College of Medicine to measure, as
      objectively as possible, both the cognitive and non-cognitive qualities of
      candidates, based on a combination of traditional screening and Objective
      Structured Interviews. This paper highlights efficacy of this selection procedure
      that includes both cognitive and non-cognitive factors, that is relevant also to
      other medical specialities. 

PMID- 24019734
TI  - A strange type of Pica.
AB  - Pica, where the patient eats non-food items such as mud, clay, varnish etc., is a
      common behavioural problem seen in children, pregnant women and the mentally
      retarded. However sponge pica is a very rare variation. We report a case of a 5
      year-old Omani girl, who presented with sponge pica since the age of two years,
      with recent abdominal pain. Investigations showed anaemia, elevated liver enzymes
      and normal intelligence. There was no evidence of obsessive-compulsive disorder.
      Both clinical and laboratory findings showed complete recovery after a few weeks
      of oral iron therapy. Her appetite improved, and she started to gain weight. No
      recurrence was observed when followed up after two years. Awareness is necessary
      to detect and treat pica as early as possible to prevent its complications. 

PMID- 24019733
TI  - How does HIV-1 infect a susceptible human cell?: Current thinking.
AB  - To insure its survival, the human immunodeficiency virus (HIV), the causative
      agent of acquired immunodeficiency syndrome (AIDS), utilises more than one gate
      to enter a target cell. This strategy makes it more difficult for the immune
      system to defeat the virus. This has also made it difficult for scientists
      working in the HIV research to understand how exactly HIV infects a susceptible
      human cell. Such understanding will no doubt open many gates for scientists to
      vanquish the virus by designing agents that can block HIV entry into target
      cells, thus rendering the virus vulnerable to immune destruction. This will also
      help in understanding the replication of the virus and the pathogenesis of the
      disease. The present article briefly describes the past and current thinking of
      how HIV-1 infects a susceptible human cell, and the dilemma scientists are facing
      when studying the infectivity of this virus and applying current knowledge to
      design agents that can block HIVs entering target cells. In the context of our
      own experience with HIV infectivity in vitro, the present article will also
      address the behaviour of different HIV isolates, both laboratory-adopted and
      clinical (primary) isolates in culture and the difficulties in performing HIV
      infectivity testing. Moreover, our experience of peripheral blood mononuclear
      cells' (PBMCs) susceptibility to HIVs infection in vitro is discussed. 

PMID- 24019735
TI  - A swallowed fishbone penetrating the oesophagus into the sternomastoid muscle.
AB  - A 40-year-old woman presented with the history of swallowing a fishbone one hour
      earlier. Since the patient was swallowing normally and the X-ray results were
      negative, she was reassured and sent home. Twenty days later, when the patient
      again presented with pain and tenderness in her neck, the fishbone was detected
      in the left sternomastoid muscle, and removed under local anaesthesia. 

PMID- 24019736
TI  - Parent Perspectives of an Evidence-Based Intervention for Children with Autism
      Served in Community Mental Health Clinics.
AB  - Research suggests that improvements to community mental health (CMH) care for
      children with autism spectrum disorders (ASD) are needed. Recent research
      examining the feasibility of training CMH therapists to deliver a package of
      evidence-based practice intervention strategies (EBPs) targeting challenging
      behaviors for school-age children with ASD offers initial support for such
      efforts to improve care. Specifically, quantitative data from a recent pilot
      study indicate that CMH therapists with limited ASD experience can deliver an EBP
      intervention with fidelity and perceive it as useful to their practice. Further,
      client attendance is high and children demonstrate improvement on standardized
      measures. To further understand the feasibility and impact of training CMH
      therapists to deliver EBPs, this mixed-methods study examined parent perspectives
      of the process and impact of outpatient psychotherapy for 13 parents of children
      ages 5-13 with ASD whose therapists were trained to deliver the EBP intervention.
      Results complement and expand previously reported quantitative data on
      psychotherapy process indicating that parents are highly involved in treatment
      for their children, perceive a strong therapeutic alliance with their children's
      therapist, and highlight that treatment was different once therapists began
      delivering the intervention. Results also indicate themes related to parents'
      perceptions of positive child and parent outcomes that provide important details
      on the specific gains that were observed during treatment. Study findings
      underscore the importance of parent perspectives in understanding the process and
      impact of implementing EBPs in CMH settings for families of children with ASD.

PMID- 24019738
TI  - Investigating Factorial Invariance of Latent Variables Across Populations When
      Manifest Variables Are Missing Completely.
AB  - Difficulties arise in multiple-group evaluations of factorial invariance if
      particular manifest variables are missing completely in certain groups. Ad hoc
      analytic alternatives can be used in such situations (e.g., deleting manifest
      variables), but some common approaches, such as multiple imputation, are not
      viable. At least 3 solutions to this problem are viable: analyzing differing sets
      of variables across groups, using pattern mixture approaches, and a new method
      using random number generation. The latter solution, proposed in this article, is
      to generate pseudo-random normal deviates for all observations for manifest
      variables that are missing completely in a given sample and then to specify
      multiple-group models in a way that respects the random nature of these values.
      An empirical example is presented in detail comparing the 3 approaches. The
      proposed solution can enable quantitative comparisons at the latent variable
      level between groups using programs that require the same number of manifest
      variables in each group.

PMID- 24019737
TI  - Therapist, Parent, and Youth Perspectives of Treatment Barriers to Family-Focused
      Community Outpatient Mental Health Services.
AB  - This exploratory qualitative study describes treatment barriers to receiving
      family-focused child mental health services for youths with disruptive behavior
      problems from multiple perspectives. Data were collected during a series of focus
      groups and interviews, including: 4 therapist focus groups, 3 parent focus
      groups, and 10 youth semi-structured interviews. Therapist, parent, and youth
      stakeholder participants discussed perceived barriers to effective treatment, the
      problems with current child outpatient therapy, and desired changes (i.e.,
      policy, intervention, etc.) to improve mental health services. Results indicate
      similar themes around treatment barriers and dissatisfaction with services within
      and across multiple stakeholder groups, including inadequate support and lack of
      family involvement; however, parents and therapists, in particular, identified
      different contributing factors to these barriers. Overall, stakeholders reported
      much frustration and dissatisfaction with current community-based outpatient
      child therapy services. Study findings can inform service provision, intervention
      development, and future research.

PMID- 24019739
TI  - Ricci Flow-based Spherical Parameterization and Surface Registration.
AB  - This paper presents an improved Euclidean Ricci flow method for spherical
      parameterization. We subsequently invent a scale space processing built upon
      Ricci energy to extract robust surface features for accurate surface
      registration. Since our method is based on the proposed Euclidean Ricci flow, it
      inherits the properties of Ricci flow such as conformality, robustness and
      intrinsicalness, facilitating efficient and effective surface mapping. Compared
      with other surface registration methods using curvature or sulci pattern, our
      method demonstrates a significant improvement for surface registration. In
      addition, Ricci energy can capture local differences for surface analysis as
      shown in the experiments and applications.

PMID- 24019740
TI  - On authentication of cell lines.

PMID- 24019741
TI  - Association transient receptor potential melastatin channel gene polymorphism
      with primary open angle glaucoma.
AB  - PURPOSE: Genetic factors are shown to have a role in the development of primary
      open angle glaucoma (POAG). The aim of this study was to determine the effects of
      genetic polymorphisms of transient receptor potential melastatin (TRPM) channel
      genes on the risk of POAG in a Turkish population. METHODS: Genomic DNA was
      extracted from the leukocytes of the peripheral blood, and 26 single nucleotide
      polymorphisms in the TRPM channel genes were analyzed in 179 patients with POAG
      and in 182 healthy controls of similar age by using the BioMark HD dynamic array
      system. RESULTS: There were marked changes in the genotype (TT, 26.8%; CT, 66.7%;
      CC, 6.5%) and allele (T, 60.1%; C, 39.9%) frequencies for the TRPM5 gene
      rs34551253 (Ala456Thr, in exon 9) polymorphism in patients when compared to the
      controls (TT, 11.3%; CT, 74.6%; CC, 14.1%, p = 0.0009; T, 48.6%; A, 51.4%, p =
      0.0063). However, no associations with the other 25 polymorphisms studied were
      found. CONCLUSIONS: This is the first study to examine the involvement of TRPM
      channel gene variations in the risk of incident POAG. This study demonstrated
      that the TRPM5 gene rs34551253 (Ala456Thr) polymorphism may be associated with
      increased risk of developing POAG in the Turkish population.

PMID- 24019742
TI  - Familial aggregation of primary open angle glaucoma in Shanghai, China.
AB  - PURPOSE: To identify familial aggregation of primary open angle glaucoma (POAG)
      in first-degree relatives in Shanghai, China. METHODS: This was a prospective
      case-control study. First-degree relatives of 113 POAG patients and 119 normal
      controls underwent a standardized ophthalmic examination. Each participant was
      diagnosed as normal, glaucoma suspect or glaucoma. The prevalence of glaucoma and
      glaucoma suspect in each group was calculated, and the odds ratio (OR) and 95%
      confidence interval (CI) for family history were estimated using the Generalized
      Estimating Equations model. RESULTS: Of 531 first-degree relatives in the case
      group, 67 (12.62%) were identified to have POAG, a rate eight times higher than
      that of the control group (8 of 526, 1.52%). In family units, the prevalence OR
      value of glaucoma was 8.77 (95% CI: 3.73-20.62). The effect of family history on
      parents, siblings, and offspring of probands was statistically significant, with
      OR values of 6.92 (95% CI: 1.90-25.18), 11.29 (95% CI: 3.63-35.11), and 11.35
      (95% CI: 1.69-76.21), respectively. In the case of glaucoma suspect, a
      significant effect was found for both family units (OR 5.60; 95% CI: 1.15-27.21)
      and offspring (10.83 OR; 95% CI: 1.34-87.73). CONCLUSIONS: In Shanghai, relatives
      of glaucoma patients have a strongly increased risk of glaucoma, and priorities
      for glaucoma screening should target this population. The study demonstrates that
      familial aggregation of POAG transcends racial and cultural boundaries.

PMID- 24019743
TI  - An epidemiological investigation of a Forkhead box protein E3 founder mutation
      underlying the high frequency of sclerocornea, aphakia, and microphthalmia in a
      Mexican village.
AB  - PURPOSE: To investigate the molecular epidemiological basis for the unusually
      high incidence of sclerocornea, aphakia, and microphthalmia in a village in the
      Tlaxcala province of central Mexico. METHODS: A population census was performed
      in a village to identify all sclerocornea, aphakia, and microphthalmia cases.
      Molecular analysis of the previously identified Forkhead box protein E3 (FOXE3)
      mutation, c.292T>C (p.Y98H), was performed with PCR amplification and direct DNA
      sequencing. In addition, DNA from 405 randomly selected unaffected villagers was
      analyzed to establish the carrier frequency of the causal mutation. To identify
      the number of generations since the mutation arose in the village, 17 polymorphic
      markers distributed in a region of 6 Mb around the mutated locus were genotyped
      in the affected individuals, followed by DMLE software analysis to calculate
      mutation age. RESULTS: A total of 22 patients with sclerocornea, aphakia, and
      microphthalmia were identified in the village, rendering a disease prevalence of
      2.52 cases per 1,000 habitants (1 in 397). The FOXE3 homozygous mutation was
      identified in all 17 affected subjects who consented to molecular analysis.
      Haplotype analysis indicated that the mutation arose 5.0-6.5 generations ago
      (approximately 106-138 years). Among the 405 unaffected villagers who were
      genotyped, ten heterozygote carriers were identified, yielding a population
      carrier frequency of approximately 1 in 40 and a predicted incidence of affected
      of 1 in 6,400 based on random marriages between two carriers in the village.
      CONCLUSIONS: This study demonstrates that a cluster of patients with
      sclerocornea, aphakia, and microphthalmia in a small Mexican village is due to a
      FOXE3 p.Y98H founder mutation that arose in the village just over a century ago
      at a time when a population migrated from a nearby village because of land
      disputes. The actual disease incidence is higher than the calculated predicted
      value and suggests non-random marriages (i.e., consanguinity) within the
      population. We can now offer the community more informed genetic counseling based
      on an accurate genetic test, thus increasing the likelihood of a better outcome
      for the families.

PMID- 24019744
TI  - A non-stop S-antigen gene mutation is associated with late onset hereditary
      retinal degeneration in dogs.
AB  - PURPOSE: To identify the causative mutation of canine progressive retinal atrophy
      (PRA) segregating as an adult onset autosomal recessive disorder in the Basenji
      breed of dog. METHODS: Basenji dogs were ascertained for the PRA phenotype by
      clinical ophthalmoscopic examination. Blood samples from six affected cases and
      three nonaffected controls were collected, and DNA extraction was used for a
      genome-wide association study using the canine HD Illumina single nucleotide
      polymorphism (SNP) array and PLINK. Positional candidate genes identified within
      the peak association signal region were evaluated. RESULTS: The highest -Log10(P)
      value of 4.65 was obtained for 12 single nucleotide polymorphisms on three
      chromosomes. Homozygosity and linkage disequilibrium analyses favored one
      chromosome, CFA25, and screening of the S-antigen (SAG) gene identified a non
      stop mutation (c.1216T>C), which would result in the addition of 25 amino acids
      (p.*405Rext*25). CONCLUSIONS: Identification of this non-stop SAG mutation in
      dogs affected with retinal degeneration establishes this canine disease as
      orthologous to Oguchi disease and SAG-associated retinitis pigmentosa in humans,
      and offers opportunities for genetic therapeutic intervention.

PMID- 24019745
TI  - The epidemiology of premature aging and associated comorbidities.
AB  - Hutchinson-Gilford Progeria Syndrome and Werner syndrome, also known as childhood
      and adulthood-progeria, respectively, represent two of the best characterized
      human progeroid diseases with clinical features mimicking physiological aging at
      an early age. The discovery of their genetic basis has led to the identification
      of several gene mutations leading to a spectrum of progeroid phenotypes ranging
      from moderate and mild-severe to very aggressive forms. In parallel, the creation
      of disease registers and databases provided available data for the design of
      relatively large-scale epidemiological studies, thereby allowing a better
      understanding of the nature and frequency of the premature aging-associated signs
      and symptoms. The aim of this article is to review the most recent findings
      concerning the epidemiology of premature aging disorders, their genetic basis,
      and the most recent reports on the frequency of associated diseases. 

PMID- 24019746
TI  - Sleep disorders and depression: brief review of the literature, case report, and
      nonpharmacologic interventions for depression.
AB  - Sleep disorders are so frequently associated with depression that, in the absence
      of sleep complaints, a diagnosis of depression should be made with caution.
      Insomnia, in particular, may occur in 60%-80% of depressed patients. Depressive
      symptoms are important risk factors for insomnia, and depression is considered an
      important comorbid condition in patients with chronic insomnia of any etiology.
      In addition, some drugs commonly prescribed for the treatment of depression may
      worsen insomnia and impair full recovery from the illness. The aim of this paper
      is to review briefly and discuss the following topics: common sleep disturbances
      during depression (in particular pavor nocturnus, nightmares, hypersomnia, and
      insomnia); circadian sleep disturbances; and treatment of depression by
      manipulation of the sleep-wake rhythm (chronotherapy, light therapy, cycles of
      sleep, and manipulation of the sleep-wake rhythm itself). Finally, we present a
      case report of a 65-year-old Caucasian woman suffering from insomnia associated
      with depression who was successfully treated with sleep deprivation. 

PMID- 24019747
TI  - The effect of cognitive status and visuospatial performance on affective theory
      of mind in Parkinson's disease.
AB  - It is now well accepted that theory of mind (ToM) functioning is impaired in
      Parkinson's disease (PD) patients. However, what remain unknown are the functions
      that underlie this impairment. It has been suggested that cognitive skills may be
      key in this area of functioning; however, many of the cognitive tests used to
      assess this have relied on intact visuospatial abilities. This study aimed to
      examine whether deficits in ToM were generated by cognitive or visuospatial
      dysfunction and the mediating effect of visuospatial function on ToM performance.
      Fifty PD patients (31 male, 19 female; mean age = 66.34 years) and 49 healthy
      controls (16 male, 33 female; mean age = 67.29 years) completed a ToM task
      (reading the mind in the eyes) and visuospatial task (line orientation). The
      results revealed that current cognitive status was a significant predictor for
      performance on the ToM task, and that 54% of the total effect of cognitive status
      on ToM was mediated by visuospatial abilities. It was concluded that visuospatial
      functioning plays an important mediating role for the relationship between
      executive dysfunction and affective ToM deficits in PD patients, and that
      visuospatial deficits may directly contribute to the presence of affective ToM
      difficulties seen in individuals with PD. 

PMID- 24019749
TI  - Bosutinib: a SRC-ABL tyrosine kinase inhibitor for treatment of chronic myeloid
      leukemia.
AB  - Bosutinib is one of five tyrosine kinase inhibitors commercially available in the
      United States for the treatment of chronic myeloid leukemia. This review of
      bosutinib summarizes the mode of action, pharmacokinetics, efficacy and safety
      data, as well as the patient-focused perspective through quality-of-life data.
      Bosutinib has shown considerable and sustained efficacy in chronic myeloid
      leukemia, especially in the chronic phase, with resistance or intolerance to
      prior tyrosine kinase inhibitors. Bosutinib has distinct but manageable adverse
      events. In the absence of T315I and V299L mutations, there are no absolute
      contraindications for the use of bosutinib in this patient population. 

PMID- 24019748
TI  - The genetics of multiple sclerosis: review of current and emerging candidates.
AB  - Multiple sclerosis (MS) is a complex disease in which environmental, genetic, and
      epigenetic factors determine the risk of developing the disease. The human
      leukocyte antigen region is the strongest susceptibility locus linked to MS, but
      it does not explain the whole heritability of the disease. To find other non
      human leukocyte antigen loci associated with the disease, high-throughput
      genotyping, sequencing, and gene-expression studies have been performed,
      producing a valuable quantity of information. An overview of the genomic and
      expression studies is provided in this review, as well as microRNA-expression
      studies, highlighting the importance of combining all the layers of information
      in order to elucidate the causes or pathological mechanisms occurring in the
      disease. Genetics in MS is a promising field that is presumably going to be very
      productive in the next decade understanding the cross talk between all the
      factors contributing to the development of MS. 

PMID- 24019750
TI  - ABCB1 haplotypes do not influence transport or efficacy of tyrosine kinase
      inhibitors in vitro.
AB  - Single-nucleotide polymorphisms (SNPs) in the gene coding for the efflux
      transport protein ABCB1 (P-glycoprotein) are commonly inherited as haplotypes.
      ABCB1 SNPs and haplotypes have been suggested to influence the pharmacokinetics
      and therapeutic outcome of the tyrosine kinase inhibitor (TKI) imatinib, used for
      treatment of chronic myeloid leukemia (CML). However, no consensus has yet been
      reached with respect to the significance of variant ABCB1 in CML treatment.
      Functional studies of variant ABCB1 transport of imatinib as well as other TKIs
      might aid the interpretation of results from in vivo association studies, but are
      currently lacking. The aim of this study was to investigate the consequences of
      ABCB1 variant haplotypes for transport and efficacy of TKIs (imatinib, its major
      metabolite N-desmethyl imatinib [CGP74588], dasatinib, nilotinib, and bosutinib)
      in CML cells. Variant haplotypes - including the 61A>G, 1199G>A, 1236C>T,
      1795G>A, 2677G>T/A, and 3435T>C SNPs - were constructed in ABCB1 complementary
      DNA and transduced to K562 cells using retroviral gene transfer. The ability of
      variant cells to express ABCB1 protein and protect against TKI cytotoxicity was
      investigated. It was found that dasatinib and the imatinib metabolite CGP74588
      are effectively transported by ABCB1, while imatinib, nilotinib, and bosutinib
      are comparatively weaker ABCB1 substrates. None of the investigated haplotypes
      altered the protective effect of ABCB1 expression against TKI cytotoxicity. These
      findings imply that the ABCB1 haplotypes investigated here are not likely to
      influence TKI pharmacokinetics or therapeutic efficacy in vivo. 

PMID- 24019752
TI  - CYP2C19 polymorphisms in the Thai population and the clinical response to
      clopidogrel in patients with atherothrombotic-risk factors.
AB  - Genetic variation in the cytochrome P450 2C19 (CYP2C19) gene has been documented
      gradually as the determinant conversion and variability in the antiplatelet
      effect of clopidogrel. The aims of this study were to determine the prevalence of
      clinically relevant allele variants (CYP2C19*2, CYP2C19*3, and CYP2C19*17) in a
      Thai study population, and finally determine whether the allele distributes and
      predicts metabolic phenotypes in clopidogrel treated patients. A total of 1,051
      Thai patients participated in this study. Genotypes for CYP2C19 polymorphisms
      were detected by the microarray-based technique. Furthermore, results of
      genotyping and platelet aggregation in 96 cardiovascular disease patients on 75
      mg clopidogrel maintenance daily dose therapy also were analyzed. Among 1,051
      samples, the allele frequencies of CYP2C19 *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and
      *1/*17 were found in 428 (40.72%), 369 (35.10%), 72 (6.85%), 77 (7.32%), 59
      (5.61%), and 45 (4.30%) of the patients, respectively. Homozygous CYP2C19 *3/*3
      was found in one patient (0.10%). Therefore, 40.72% of the patients were
      predicted as extensive metabolizers, 41.95% as intermediate metabolizers, 13.03%
      as poor metabolizers, and 4.30% as ultra-rapid metabolizers. Among 96 patients,
      the frequency of poor metabolizers was significantly higher in the clopidogrel
      non-responder group than in the responder group (36.0% and 15.5%, respectively, P
      = 0.03). CYP2C19*1/*17 was observed in responders (n = 2; 2.8%). As a result,
      CYP2C19 variants were associated with clopidogrel non-responders. However, there
      is a need for further elucidation of the clinical importance and use of this
      finding to make firm and cost-effective recommendations for drug treatment in the
      future. 

PMID- 24019753
TI  - Association of CYP3A4/5, ABCB1 and ABCC2 polymorphisms and clinical outcomes of
      Thai breast cancer patients treated with tamoxifen.
AB  - BACKGROUND: Pharmacogenetic study of cytochrome P450 (CYP) gene CYP2D6 and
      tamoxifen outcomes remain controversial. Apart from CYP2D6, other drug
      metabolizing enzymes and transporters also play a role in tamoxifen metabolic
      pathways. The aim of this study is to investigate the impact of CYP3A4/5, ABCB1,
      and ABCC2 polymorphisms on the risk of recurrence in Thai patients who received
      tamoxifen adjuvant therapy. METHODS: Patients with early-stage breast cancer who
      received tamoxifen adjuvant therapy were recruited in this study. All six single
      nucleotide polymorphisms (SNPs), including CYP3A4*1B (-392 A>G)/*18(878 T>C),
      CYP3A5*3(6986 G>A), ABCB1 3435 C>T, ABCC2*1C(-24 C>T), and ABCC2 68231 A>G, were
      genotyped using real-time polymerase chain reaction assays. The impacts of
      genetic variants on disease-free survival (DFS) were analyzed using the Kaplan
      Meier method and Cox regression analysis. RESULTS: The ABCB1 3435 C>T was found
      to have the highest allele frequency among other variants; however, CYP3A4*1B/*18
      could not be found in this study. Patients with heterozygous ABCB1 3435 CT
      genotype showed significantly shorter DFS than those with homozygous 3435 CC
      genotype (P = 0.041). In contrast, patients who carried homozygous 3435 TT
      genotype showed no difference in DFS from wild-type 3435 CC patients. Cox
      regression analysis showed that the relative risk of recurrence was increased by
      five times (P = 0.043; hazard ratio = 5.11; 95% confidence interval: 1.05-24.74)
      in those patients carrying ABCB1 3435 CT genotype compared to those with ABCB1
      3435 CC. CONCLUSION: ABCB1 3435 C>T is likely to have a clinically significant
      impact on recurrence risk in Thai patients with breast cancer who receive
      tamoxifen adjuvant therapy.

PMID- 24019751
TI  - Role of biomarkers in understanding and treating children with asthma: towards
      personalized care.
AB  - Asthma is one of the most common chronic diseases affecting children. Despite
      publicized expert panels on asthma management and the availability of high
      potency inhaled corticosteroids, asthma continues to pose an enormous burden on
      quality of life for children. Research into the genetic and molecular origins of
      asthma are starting to show how distinct disease entities exist within the
      syndrome of "asthma". Biomarkers can be used to diagnose underlying molecular
      mechanisms that can predict the natural course of disease or likely response to
      drug treatment. The progress of personalized medicine in the care of children
      with asthma is still in its infancy. We are not yet able to apply stratified
      asthma treatments based on molecular phenotypes, although that time may be fast
      approaching. This review discusses some of the recent advances in asthma genetics
      and the use of current biomarkers that can help guide improved treatment. For
      example, the fraction of expired nitric oxide and serum Immunoglobulin E (IgE)
      (including allergen-specific IgE), when evaluated in the context of recurrent
      asthma symptoms, are general predictors of allergic airway inflammation.
      Biomarker assays for secondhand tobacco smoke exposure and cysteinyl leukotrienes
      are both promising areas of study that can help personalize management, not just
      for pharmacologic management, but also education and prevention efforts. 

PMID- 24019754
TI  - Restoring proximal caries lesions conservatively with tunnel restorations.
AB  - The tunnel restoration has been suggested as a conservative alternative to the
      conventional box preparation for treating proximal caries. The main advantage of
      tunnel restoration over the conventional box or slot preparation includes being
      more conservative and increasing tooth integrity and strength by preserving the
      marginal ridge. However, tunnel restoration is technique-sensitive and can be
      particularly challenging for inexperienced restorative dentists. Recent advances
      in technology, such as the contemporary design of dental handpieces with advanced
      light-emitting diode (LED) and handheld comfort, offer operative dentists better
      vision, illumination, and maneuverability. The use of magnifying loupes also
      enhances the visibility of the preparation. The advent of digital radiographic
      imaging has improved dental imaging and reduced radiation. The new generation of
      restorative materials has improved mechanical properties. Tunnel restoration can
      be an option to restore proximal caries if the dentist performs proper case
      selection and pays attention to the details of the restorative procedures. This
      paper describes the clinical technique of tunnel restoration and reviews the
      studies of tunnel restorations. 

PMID- 24019755
TI  - Current strategies to minimize the bleeding risk of warfarin.
AB  - For many decades, the vitamin K antagonist warfarin has been the mainstay of
      treatment for various conditions that require anticoagulation, including atrial
      fibrillation. Although the efficacy of warfarin in both prevention and treatment
      of thrombosis has been demonstrated in numerous randomized clinical studies, one
      of the major concerns that remains is the risk of bleeding. Although the net
      benefit of warfarin has been demonstrated in large clinical trials, physicians
      and patients alike are often reluctant to use warfarin because of the bleeding
      risk. Bleeding in patients on warfarin is generally minor requiring no
      intervention, but the development of a major bleeding complication is associated
      with significant morbidity and can even be fatal. Numerous risk factors that
      increase the probability of having a hemorrhage while on warfarin have been
      identified, and bleeding risk scores have been developed. Various strategies to
      reduce bleeding risks have been developed and have become more important, since
      the use of warfarin and other anticoagulants continues to increase. This paper
      provides a concise review of bleeding risk factors, while outlining
      recommendations both physician and patients can incorporate to help reduce the
      risk of bleeding. 

PMID- 24019756
TI  - Lost branches on the tree of life.

PMID- 24019757
TI  - Deacetylation ensures timely regulation of flowering.

PMID- 24019758
TI  - Analysis of the RelA:CBP/p300 interaction reveals its involvement in NF-kappaB
      driven transcription.
AB  - NF-kappaB plays a vital role in cellular immune and inflammatory response,
      survival, and proliferation by regulating the transcription of various genes
      involved in these processes. To activate transcription, RelA (a prominent NF
      kappaB family member) interacts with transcriptional co-activators like CREB
      binding protein (CBP) and its paralog p300 in addition to its cognate kappaB
      sites on the promoter/enhancer regions of DNA. The RelA:CBP/p300 complex is
      comprised of two components--first, DNA binding domain of RelA interacts with the
      KIX domain of CBP/p300, and second, the transcriptional activation domain (TAD)
      of RelA binds to the TAZ1 domain of CBP/p300. A phosphorylation event of a well
      conserved RelA(Ser276) is prerequisite for the former interaction to occur and is
      considered a decisive factor for the overall RelA:CBP/p300 interaction. The role
      of the latter interaction in the transcription of RelA-activated genes remains
      unclear. Here we provide the solution structure of the latter component of the
      RelA:CBP complex by NMR spectroscopy. The structure reveals the folding of RelA
      TA2 (a section of TAD) upon binding to TAZ1 through its well-conserved
      hydrophobic sites in a series of grooves on the TAZ1 surface. The structural
      analysis coupled with the mechanistic studies by mutational and isothermal
      calorimetric analyses allowed the design of RelA-mutants that selectively
      abrogated the two distinct components of the RelA:CBP/p300 interaction. Detailed
      studies of these RelA mutants using cell-based techniques, mathematical modeling,
      and genome-wide gene expression analysis showed that a major set of the RelA
      activated genes, larger than previously believed, is affected by this
      interaction. We further show how the RelA:CBP/p300 interaction controls the
      nuclear response of NF-kappaB through the negative feedback loop of NF-kappaB
      pathway. Additionally, chromatin analyses of RelA target gene promoters showed
      constitutive recruitment of CBP/p300, thus indicating a possible role of CBP/p300
      in recruitment of RelA to its target promoter sites.

PMID- 24019759
TI  - A meiosis-specific form of the APC/C promotes the oocyte-to-embryo transition by
      decreasing levels of the Polo kinase inhibitor matrimony.
AB  - Oocytes are stockpiled with proteins and mRNA that are required to drive the
      initial mitotic divisions of embryogenesis. But are there proteins specific to
      meiosis whose levels must be decreased to begin embryogenesis properly? The
      Drosophila protein Cortex (Cort) is a female, meiosis-specific activator of the
      Anaphase Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase. We
      performed immunoprecipitation of Cortex followed by mass spectrometry, and
      identified the Polo kinase inhibitor Matrimony (Mtrm) as a potential interactor
      with Cort. In vitro binding assays showed Mtrm and Cort can bind directly. We
      found Mtrm protein levels to be reduced dramatically during the oocyte-to-embryo
      transition, and this downregulation did not take place in cort mutant eggs,
      consistent with Mtrm being a substrate of APC(Cort). We showed that Mtrm is
      subject to APC(Cort)-mediated proteasomal degradation and have identified a
      putative APC/C recognition motif in Mtrm that when mutated partially stabilized
      the protein in the embryo. Furthermore, overexpression of Mtrm in the early
      embryo caused aberrant nuclear divisions and developmental defects, and these
      were enhanced by decreasing levels of active Polo. These data indicate APC(Cort)
      ubiquitylates Mtrm at the oocyte-to-embryo transition, thus preventing excessive
      inhibition of Polo kinase activity due to Mtrm's presence. 

PMID- 24019761
TI  - Preconception care in low- and middle-income countries: new opportunities and a
      new metric.

PMID- 24019760
TI  - Photoperiodic regulation of flowering time through periodic histone deacetylation
      of the florigen gene FT.
AB  - The developmental transition from a vegetative to a reproductive phase (i.e.,
      flowering) is timed by the seasonal cue day length or photoperiod in many plant
      species. Through the photoperiod pathway, inductive day lengths trigger the
      production of a systemic flowering signal, florigen, to provoke the floral
      transition. FLOWERING LOCUS T (FT), widely conserved in angiosperms, is a major
      component of the mobile florigen. In the long-day plant Arabidopsis, FT
      expression is rhythmically activated by the output of the photoperiod pathway
      CONSTANS (CO), specifically at the end of long days. How FT expression is
      modulated at an adequate level in response to the long-day cue to set a proper
      flowering time remains unknown. Here, we report a periodic histone deacetylation
      mechanism for the photoperiodic modulation of FT expression. We have identified a
      plant-unique core structural component of an Arabidopsis histone deacetylase
      (HDAC) complex. In long days, this component accumulates at dusk, and is
      recruited by a MADS-domain transcription factor to the FT locus specifically at
      the end of the day, leading to periodic histone deacetylation of FT chromatin at
      dusk. Furthermore, we found that at the end of long days CO activity not only
      activates FT expression but also enables HDAC-activity recruitment to FT
      chromatin to dampen the level of FT expression, and so prevent precocious
      flowering in response to the inductive long-day cue. These results collectively
      reveal a periodic histone deacetylation mechanism for the day-length control of
      flowering time in higher plants. 

PMID- 24019762
TI  - Setting research priorities for preconception care in low- and middle-income
      countries: aiming to reduce maternal and child mortality and morbidity.

PMID- 24019763
TI  - Association of the ANRS-12126 male circumcision project with HIV levels among men
      in a South African township: evaluation of effectiveness using cross-sectional
      surveys.
AB  - BACKGROUND: Randomized controlled trials have shown that voluntary medical male
      circumcision (VMMC) reduces HIV infection by 50% to 60% in sub-Saharan African
      populations; however, little is known about the population-level effect of adult
      male circumcision (MC) as an HIV prevention method. We assessed the effectiveness
      of VMMC roll-out on the levels of HIV in the South African township of Orange
      Farm where the first randomized controlled trial (RCT) to test the effect of VMMC
      on HIV acquisition was conducted in 2002-2005. METHODS AND FINDINGS: The Bophelo
      Pele project is a community-based campaign against HIV, which includes the roll
      out of free VMMC. A baseline cross-sectional biomedical survey was conducted in
      2007-2008 among a random sample of 1,998 men aged 15 to 49 (survey response rate
      80.7%). In 2010-2011, we conducted a follow-up random survey among 3,338 men aged
      15 to 49 (survey response rate 79.6%) to evaluate the project. Participants were
      interviewed, blood samples were collected and tested for HIV and recent HIV
      infection (using the BED HIV incidence assay), and MC status was assessed through
      a clinical examination. Data were analyzed using multivariate and propensity
      statistical methods. Owing to the VMMCs performed in the context of the RCT and
      the Bophelo Pele project, the prevalence rate of adult MC increased from 0.12
      (95% CI 0.10-0.14) to 0.53 (95% CI 0.51-0.55). Without these VMMCs, the HIV
      prevalence rate in 2010-2011 would have been 19% (95% CI 12%-26%) higher (0.147
      instead of 0.123). When comparing circumcised and uncircumcised men, no
      association of MC status with sexual behavior was detected. Among circumcised and
      uncircumcised men, the proportion consistently using condoms with non-spousal
      partners in the past 12 months was 44.0% (95% CI 41.7%-46.5%) versus 45.4% (95%
      CI 42.2%-48.6%) with weighted prevalence rate ratio (wPRR) = 0.94 (95% CI 0.85
      1.03). The proportion having two or more non-spousal partners was 50.4% (95% CI
      47.9%-52.9%) versus 44.2% (95% CI 41.3%-46.9%) with wPRR = 1.03 (95% CI 0.95
      1.10). We found a reduction of BED-estimated HIV incidence rate ranging from 57%
      (95% CI 29%-76%) to 61% (95% CI 14%-83%) among circumcised men in comparison with
      uncircumcised men. CONCLUSIONS: Findings suggest that the roll-out of VMMC in
      Orange Farm is associated with a significant reduction of HIV levels in the
      community. The main limitation of the study is that it was not randomized and
      cannot prove a causal association. The roll-out of VMMC among adults in sub
      Saharan Africa should be an international priority and needs to be accelerated to
      effectively combat the spread of HIV. Please see later in the article for the
      Editors' Summary.

PMID- 24019764
TI  - Extraperitoneal Fluid Collection due to Chronic Pancreatitis.
AB  - A 39-year-old man was referred to our hospital for the investigation of abdominal
      fluid collection. He was pointed out to have alcoholic chronic pancreatitis.
      Laboratory data showed inflammation and slightly elevated serum direct bilirubin
      and amylase. An abdominal computed tomography demonstrated huge fluid collection,
      multiple pancreatic pseudocysts and pancreatic calcification. The fluid showed a
      high level of amylase at 4,490 IU/l. Under the diagnosis of pancreatic ascites,
      endoscopic pancreatic stent insertion was attempted but was unsuccessful, so
      surgical treatment (Frey procedure and cystojejunostomy) was performed. During
      the operation, a huge amount of fluid containing bile acid (amylase at 1,474 IU/l
      and bilirubin at 13.5 mg/dl) was found to exist in the extraperitoneal space
      (over the peritoneum), but no ascites was found. His postoperative course was
      uneventful and he shows no recurrence of the fluid. Pancreatic ascites is thought
      to result from the disruption of the main pancreatic duct, the rupture of a
      pancreatic pseudocyst, or possibly leakage from an unknown site. In our extremely
      rare case, the pancreatic pseudocyst penetrated into the hepatoduodenal ligament
      with communication to the common bile duct, and the fluid flowed into the round
      ligament of the liver and next into the extraperitoneal space. 

PMID- 24019765
TI  - Multiple liver lesions in an immunosuppressed patient: is infection always the
      answer?
AB  - Pylephlebitis with associated liver abscesses is a rare complication of Crohn's
      disease that usually presents in the setting of active disease and recent
      escalation of the immunosuppressive regimen. Here we describe a 17-year-old
      female patient with active Crohn's disease who presented with a clinical picture
      and hepatic radiographic findings concerning for pylephlebitis and associated
      liver abscesses but subsequently confirmed to be an atypical form of focal fatty
      liver infiltration. We describe the diagnostic difficulty this unique
      distribution of hepatic fatty infiltration can present and highlight the
      importance of the different imaging studies to differentiate between atypical
      focal fatty infiltration and pylephlebitis. 

PMID- 24019766
TI  - Incidence of pancreatic fistula after distal pancreatectomy and efficacy of
      endoscopic therapy for its management: results from a tertiary care center.
AB  - Pancreatic fistula is a known complication of distal pancreatectomy. Endotherapy
      with pancreatic duct stent placement and pancreatic sphincterotomy has been shown
      to be effective in its management; however, experience of endotherapy in the
      management of this complication has not been extensively reported from the United
      States. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) with
      pancreatic stent placement has also been proposed to prevent this complication
      after distal pancreatectomy. In our cohort of 59 patients who underwent distal
      pancreatectomy, 13 (22%) developed a pancreatic fistula in the immediate
      postoperative period, of whom 8 (14%) patients (5 female, mean age 52 years) were
      referred for an ERCP because of ongoing symptoms related to the pancreatic
      fistula. The pancreatic fistula resolved in all patients after a median duration
      of 62 days from the index ERCP. The median number of ERCPs required to document
      resolution of the pancreatic fistula was 2. Although a sizeable percentage of
      patients develop a pancreatic fistula after distal pancreatectomy, only a small
      percentage of patients require ERCP for management of this complication. Given
      the high success rate of endotherapy in resolving pancreatic fistula and the fact
      that the majority of patients who undergo distal pancreatectomy never require an
      ERCP, performing ERCP for prophylactic pancreatic duct stent prior to distal
      pancreatectomy might not be necessary. 

PMID- 24019767
TI  - A case of adult type 1 Gaucher disease complicated by temporal intestinal
      hemorrhage.
AB  - A 21-year-old man with a history of sudden rectal hemorrhage was referred to our
      hospital. Examination disclosed thrombocytopenia and hepatosplenomegaly. A liver
      biopsy specimen demonstrated Gaucher cells in Glisson's capsule. Additional
      investigations revealed a low level of leukocyte beta-glucosidase activity and
      common mutations of the glucocerebrosidase gene, L444P/D409H. We diagnosed the
      patient with Gaucher disease type 1. He underwent enzyme replacement therapy.
      Thrombocytopenia and hepatosplenomegaly improved at a rate of approximately 50
      and 20%, respectively, within 6 months. This case suggests that we must pay
      attention to adult Gaucher disease as a differential diagnosis for cryptogenic
      thrombocytopenia. 

PMID- 24019768
TI  - A phrygian cap.
AB  - A Phrygian cap is a congenital anomaly of the gallbladder with an incidence of
      4%. It can simulate a mass in the liver during hepatobiliary imaging and is
      sometimes mistaken for pathology. A Phrygian cap, however, has no pathological
      significance and normally causes no symptoms. A case will be presented where a
      Phrygian cap was found by coincidence during surgery. The patient was operated
      for colon cancer with liver metastasis in segment V. He underwent a simultaneous
      right hemicolectomy and wedge resection of the liver lesion. During perioperative
      inspection, a gallbladder with a folded fundus was seen. This deformity was, in
      retrospective, detected on the preoperative MRI scan. The patient underwent
      cholecystectomy to make the wedge resection easier to perform. Otherwise,
      cholecystectomy for a Phrygian cap is only indicated in case of symptoms.
      Radiographic imaging can be helpful in narrowing the differential diagnosis. To
      our knowledge, there is no recent literature about the Phrygian cap and its
      imaging aspects. Nowadays, multiphase MRI, or multiphase CT in case of MRI
      contraindication, are the first choices of hepatobiliary imaging. 

PMID- 24019769
TI  - Tumor-like growth of giant inflammatory polyposis in a patient with ulcerative
      colitis.
AB  - We report a unique case of giant obstructing inflammatory polyposis associated
      with ulcerative colitis (UC). A 25-year-old Japanese man with an UC history of 2
      years and 6 months was referred to our institution because of diarrhea and
      melena. His computed tomography scan showed marked dilation of the transverse and
      descending colon; therefore, we performed total colectomy. Macroscopic evaluation
      of the excised specimen indicated constricting lesions with giant polyposis in
      the transverse and descending colon. The polyposis consisted of narrow worm- or
      noodle-like polyps that bridged over the irregular ulcers. Histologic evaluation
      of the excised specimen indicated transmural inflammation with a thickened proper
      muscular layer overlaid with inflammatory polyposis. Based on these data, a
      diagnosis of giant inflammatory polyposis should be considered in patients who
      have had UC. Although giant inflammatory polyposis is considered benign, surgical
      treatment may be indicated to avoid serious complications. 

PMID- 24019770
TI  - Familial adenomatous polyposis and Crohn's disease in one patient: dilemmas and
      concerns.
AB  - Familial adenomatous polyposis (FAP) and Crohn's disease (CD) are two entities
      with no known etiologic or physiopathogenic relation. The rarity of the former
      makes the coincidence of both diagnoses in one patient very unlikely.
      Nevertheless, management in such cases can be puzzling as surgical options must
      be considered, and immunosuppression/immunomodulation is set in a territory of
      accelerated carcinogenesis. We report the case of a 29-year-old male with a
      diagnosis of FAP since adolescence, already submitted to prophylactic
      proctocolectomy, presenting with anemia and bloody diarrhea, revealing small
      bowel CD. This case allows for a rich discussion of the clinical dilemmas
      presenting when FAP and CD are diagnosed in the same patient and for a deep
      analysis of the concerns inherent to the available therapeutic options. 

PMID- 24019771
TI  - Coxsackievirus A6 and Hand, Foot and Mouth Disease: Three Case Reports of
      Familial Child-to-Immunocompetent Adult Transmission and a Literature Review.
AB  - Hand, foot and mouth disease (HFMD) is a highly contagious viral infection
      characterized by typical maculopapular or vesicular eruptions on the hands and
      feet and in the oral cavity. It affects predominantly children and/or
      immunocompromised adults. It usually follows a benign and self-limiting course.
      However, HFMD cases with severe or lethal complications such as encephalitis,
      meningitis, pulmonary edema and myocarditis have also been reported, mostly in
      children, but also in adults. High infectivity of HFMD has contributed to several
      large outbreaks of this disease in recent decades in East and Southeast Asia, the
      United States and Finland. The most common pathogens were Coxsackievirus A16,
      Enterovirus 71 and, recently, also Coxsackieviruses A6 and A10. Differences in
      the course of HFMD have been observed, depending on the virus type. Recently,
      many cases of atypical HFMD have been described in the literature with unusual
      morphology and/or localization of skin lesions. Atypical HFMD manifestations
      including vesiculobullous exanthema, often on the trunk or extremities, and
      perioral zone involvement were often caused by Coxsackievirus A6 infections. We
      present 3 cases of familial transmission of HFMD caused by Coxsackievirus A6 with
      some atypical features, benign course and complete recovery among immunocompetent
      adults. 

PMID- 24019772
TI  - Acral peeling skin syndrome resembling epidermolysis bullosa simplex in a 10
      month-old boy.
AB  - The acral peeling skin syndrome (APSS) is a rare autosomal recessive disorder
      clinically characterized by asymptomatic desquamation of the skin limited to the
      hands and feet and histologically by cleavage at the stratum granulosum and
      stratum corneum level [Kiritsi et al.: J Invest Dermatol 2010;130:1741-1746]. We
      report on a 10-month-old boy with a history of skin peeling limited to the hands
      and feet since 2 months of age. Clinical examination revealed erythematous
      erosions with peripheral desquamation and flaccid blisters. DNA mutation analysis
      detected two heterozygous TGM5 mutations: c.2T>C, p.M1T in exon 1 and c.337G>T,
      p.G113C in exon 3 in keeping with the diagnosis of APSS. The clinical
      presentation of APSS alone might be confusing and strongly resemble epidermolysis
      bullosa simplex making the differential diagnosis difficult. 

PMID- 24019773
TI  - Signet-ring cutaneous squamous cell carcinoma arising on the back of the finger.
AB  - A variety of pathologic variants of cutaneous squamous cell carcinoma (SCC) has
      been reported, and the signet-ring variant of cutaneous SCC is extremely
      uncommon. We reported an 83-year-old man with signet-ring SCC arising on the back
      of the finger. As far as we know, only 4 cases have been described in detail, and
      one dermatopathologic report focused on the presence of signet-ring cells briefly
      described in clinical data of 6 cases. Interestingly, in these reports, the skin
      lesions of 10 cases occurred exclusively in the head and neck area. This case
      involved a skin lesion on the back of the finger and is thus the first reported
      case of signet-cell cutaneous SCC that did not arise in the head and neck area.
      The location of this lesion, together with the histological findings compatible
      with actinic keratosis, support the hypothesis that the development of signet
      ring SCC is related to ultraviolet light-induced damage. 

PMID- 24019775
TI  - Diphenylcyclopropenone-induced vitiligo in a patient with alopecia universalis.
AB  - Alopecia areata and vitiligo are autoimmune diseases, both associated with
      multiple autoimmune comorbidities. Many studies show colocalization of these
      diseases at the same anatomical site. Here, we have a case where both disorders
      were reported to present in the same patient. Diphenylcyclopropenone
      (diphencyprone, DCP) is used in the treatment of alopecia areata and may induce
      vitiligo in some patients. We report on one case of vitiligo that was induced by
      DCP during therapy for alopecia universalis. Alopecia areata and vitiligo share
      many susceptibility genes. Follicular melanocyte destruction may represent the
      link between the two diseases. 

PMID- 24019774
TI  - Hepatitis and Lupus-Like Syndrome during Infliximab Therapy for Psoriasis.
AB  - Biologics are very useful medications that changed the lives of many patients in
      the last decade. However, we still do not know about the long-term side effects
      of these drugs. Infliximab is an anti-TNF chimeric antibody widely used and
      approved for the treatment of many diseases. Lupus-like syndrome and hepatitis
      are among the uncommon side effects of infliximab. Most of the written literature
      was published for cases of rheumatology and gastroenterology. We report here a
      case of both hepatitis and lupus-like syndrome that occurred sequentially in the
      same patient and compare our finding with two case reports of the same side
      effects, drug and disease. 

PMID- 24019776
TI  - Subacute cutaneous lupus erythematosus triggered by radiotherapy.
AB  - BACKGROUND: The origin of collagen autoimmune diseases is not fully understood.
      Some studies postulate a mechanism of molecular mimicry or heterologous immunity
      following viral infections triggering autoimmunity. Apart from infections, other
      exogenous factors such as visible light or X-rays have been reported to incite
      autoimmunity. CASE REPORT: We report a case of histologically and serologically
      confirmed subacute lupus erythematosus (SCLE) following radiotherapy for breast
      cancer. DISCUSSION: The close temporal and spatial correlation between
      radiotherapy and onset of SCLE in this patient suggests that an autoimmune
      reaction may have been triggered locally by functionally altering the immune
      system and breaking self-tolerance.

PMID- 24019777
TI  - Herpes simplex virus type-I and pyogenic granuloma: a vascular endothelial growth
      factor-mediated association?
AB  - Pyogenic granuloma (PG) is a vascular endothelial growth factor (VEGF)-related
      neoangiogenic process. Minor trauma, chronic irritation, certain drugs and
      pregnancy may favor PG. Viral triggers have not been reported up to date. A 52
      year-old woman with hairy-cell leukemia presented because of a 3-month history of
      a giant pseudotumoral lesion on her left cheek. All prior antibacterial,
      antifungal and anti-inflammatory treatments had failed. Histology revealed PG
      with sparse and isolated epithelial cell aggregates. Immunohistochemistry (IHC)
      identified herpes simplex virus type-I (HSV-I) antigens in the nuclei and
      cytoplasm of normal-appearing as well as cytopathic epithelial cells, suggesting
      a chronic, low-productive HSV infection. No HSV-I signal was evidenced in the
      endothelial cells of the PG. Furthermore, IHC revealed VEGF in the HSV-I infected
      epithelial cells as well as within the PG endothelial cells. These results
      incited oral treatment with valaciclovir, and the PG promptly resolved after 2
      weeks. These findings suggest that a chronic HSV-I infection might play an
      indirect, partial role in neoangiogenesis, presumably via HSV-I infection-related
      stimulation of keratinocytic VEGF production. 

PMID- 24019778
TI  - Severe acute rhabdomyolysis induced by multi-agent chemotherapy for alveolar
      rhabdomyosarcoma in a 15-year-old female: a case report.
AB  - This is the first paper to report the association of cancer chemotherapy with
      rhabdomyolysis in children. A previously healthy, 15-year-old Japanese female was
      diagnosed as having alveolar rhabdomyosarcoma. She received the first cycle of
      multi-agent chemotherapy without any adverse effects. However, she developed
      severe acute rhabdomyolysis shortly after the second cycle of multi-agent
      chemotherapy, which consisted of etoposide, ifosfamide, actinomycin-D and
      vincristine. Her condition deteriorated rapidly and she was treated with
      mechanical ventilation and fluid replacement. After further evaluation,
      anticancer drugs were thought to be responsible for the rhabdomyolysis. 

PMID- 24019779
TI  - Posttraumatic glioma: report of a case.
AB  - For a long time, head injury has been considered as a possible causative factor
      for later development of brain tumors. However, the actual role of previous head
      trauma in the pathogenesis of intracranial tumors is still a matter of debate,
      also due to the possible medico-legal implications. Some authors have suggested
      several criteria for establishing a possible causal relationship between the
      aforementioned factors. We report a case of a left posterior paraventricular high
      grade glioma which developed 20 years after a posttraumatic hematoma occurring in
      the same area. This case is reported in detail and the relevant literature is
      reviewed. 

PMID- 24019780
TI  - Aspergillosis in a patient receiving temozolomide for the treatment of
      glioblastoma.
AB  - Leukopenia and selective CD4+ lymphopenia represent major adverse events
      associated with the use of temozolomide (TMZ), an oral alkylating agent
      incorporated in the treatment of glioblastoma (GBM). The increased risk of
      opportunistic infections, including those caused by Pneumocystis jiroveci and
      cytomegalovirus, has been previously described in the literature. Here we report
      the case, the first to our knowledge, of a patient with pulmonary invasive
      aspergillosis immediately after the completion of chemoradiation with TMZ for
      GBM. Diagnosis was confirmed through a CT-guided lung biopsy, and the patient had
      excellent response to systemic voriconazole. This case illustrates that TMZ can
      be associated with severe opportunistic infections, presumably associated with T
      lymphocyte immune dysfunction, and patients exposed to this agent should be
      carefully monitored. 

PMID- 24019781
TI  - Skull base clear cell carcinoma, metastasis of renal primary tumor: a case report
      and literature review.
AB  - We report on a patient who presented with cranial nerve VI bilateral paresis,
      absence of pharyngeal reflex, dysarthria, right tongue deviation, and right
      facial paralysis. Imaging studies showed an expansive process in the cranial base
      with clivus and petrous apex osteolysis. A biopsy confirmed the presence of clear
      cell adenocarcinoma and suspicion of renal tumor metastases. Abdominal imaging
      studies revealed a mass in the right kidney. Consequently, radiotherapy was
      performed, and the patient was enrolled in a palliative care and pain control
      program. 

PMID- 24019782
TI  - Total Reconstruction of the Afferent Loop for Treatment of Radiation-Induced
      Afferent Loop Obstruction with Segmental Involvement after
      Pancreaticoduodenectomy with Roux-en-Y Reconstruction.
AB  - As the literature on afferent loop obstruction (ALO) after
      pancreaticoduodenectomy (PD) is very limited, standardized rules for its
      management do not exist. Herein, we report the case of a 65-year-old male patient
      with chronic ALO who had undergone PD with single Roux-en-Y limb reconstruction
      and adjuvant chemoradiation therapy for pancreatic head adenocarcinoma 2 years
      earlier. The patient was brought to the operating room with the diagnosis of
      radiation enteritis of the afferent loop with segmental involvement and
      concurrent hepaticojejunostomy (HJ) and pancreaticojejunostomy (PJ) stricture.
      Complete mobilization of the afferent loop, removal of the affected segment and
      reconstruction were performed. Reconstruction of the afferent loop was a one-way
      option for the surgeons because the Roux-en-Y reconstruction limited endoscopic
      access to the afferent loop, and the segmental radiation injury of the afferent
      loop ruled out bypass surgery. However, mobilization of the affected segment
      through a field of dense adhesions and revision of the HJ and PJ were technically
      demanding. 

PMID- 24019783
TI  - Disease flare after discontinuation of crizotinib in anaplastic lymphoma kinase
      positive lung cancer.
AB  - We report the case of a 50-year-old male former smoker. He was diagnosed as
      having lung adenocarcinoma and treated with induction chemoradiation therapy
      followed by surgery and adjuvant chemotherapy. Molecular testing revealed that
      his tumor had an echinoderm microtubule-associated protein-like 4-anaplastic
      lymphoma kinase (EML4-ALK) rearrangement. Therefore, he was treated with
      crizotinib when his disease recurred. He achieved a partial response, which
      persisted for 10 months until progressive disease was confirmed. Crizotinib was
      continued for 1 month and the tumor size increased slightly. At that time,
      crizotinib was discontinued and he participated in a clinical trial of erlotinib
      +/- Met inhibitor; however, his disease progressed rapidly after discontinuation
      of crizotinib, and the diagnosis of disease flare was made. Readministration of
      crizotinib was started immediately; however, his disease progressed rapidly, and
      he died 2 days after starting crizotinib retreatment. Currently, the incidence of
      disease flare is unknown and it is impossible to predict who will experience it.
      Therefore, continuing crizotinib after disease progression may be a reasonable
      option to avoid disease flare. 

PMID- 24019784
TI  - Bevacizumab is Effective for Recurrent Papillary Tumor of the Pineal Region:
      First Report.
AB  - Papillary tumor of the pineal region (PTPR) is a rare brain tumor that probably
      arises from ependymal cells. There are no known systemic treatments for PTPR once
      it is refractory to surgery and radiation. We present the first case of a durable
      radiographic and clinical response of a PTPR to bevacizumab, an antibody against
      vascular endothelial growth factor, despite multiple prior treatments.
      Bevacizumab may be an effective treatment for PTPR. 

PMID- 24019785
TI  - Prolonged clinical benefit of everolimus therapy in the management of high-grade
      pancreatic neuroendocrine carcinoma.
AB  - Treatment options for patients with high-grade pancreatic neuroendocrine tumors
      (pNET) are limited, especially for those with progressive disease and for those
      who experience treatment failure. Everolimus, an oral inhibitor of mammalian
      target of rapamycin (mTOR), has been approved for the treatment of patients with
      low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3
      study in patients with low- or intermediate-grade advanced pNET, everolimus
      significantly increased progression-free survival (PFS) and decreased the
      relative risk for disease progression by 65% over placebo. This case report
      describes a heavily pretreated patient with high-grade pNET and liver and
      peritoneal metastases who achieved prolonged PFS, clinically relevant partial
      radiologic tumor response, and resolution of constitutional symptoms with
      improvement in Karnofsky performance status while receiving a combination of
      everolimus and octreotide long-acting repeatable (LAR). Radiologic and clinical
      responses were maintained for 19 months, with minimal toxicity over the course of
      treatment. This case supports the findings that the combination of everolimus
      plus octreotide LAR may be considered for use in patients with high-grade pNET
      and progressive disease. Although behavior and aggressiveness are different
      between low- or intermediate-grade and high-grade pNET, some high-grade pNET may
      express mTOR; hence, everolimus should be considered in a clinical trial. 

PMID- 24019786
TI  - Reversible Isolated Accessory Nerve Palsy due to a Large Thrombosed Vertebral
      Aneurysm.
AB  - OBJECTIVE: Isolated accessory nerve palsy due to intracranial disorders is
      uncommon because intracranial accessory nerve injury usually occurs in case of a
      skull base tumor or trauma, resulting in one of multiple cranial nerve palsies.
      We report a very rare case of isolated accessory nerve palsy due to a large
      thrombosed aneurysm of the intracranial vertebral artery. Full recovery was
      achieved after surgery. CASE REPORT: A patient complaining of transient numbness
      in the right side was referred to our hospital. An MRI indicated a large
      thrombosed aneurysm of the right vertebral artery. The aneurysm severely
      compressed the medulla oblongata. First, the proximal vertebral artery (VA) was
      clipped with an aneurysm clip to reduce the pressure inside the aneurysm.
      However, cerebral angiography revealed a partial recanalization of the right VA.
      The patient then underwent coil embolization of the right VA just proximal to the
      aneurysm clip. Subsequently, the right VA was completely obliterated. The patient
      was discharged without any neurological deficit. Two weeks later, however, she
      complained of right shoulder pain. Physical and neurological examinations
      demonstrated atrophy of the right trapezius and sternocleidomastoid muscle,
      leading to a deepening of the right supraclavicular fossa. The symptoms were
      considered to result from the right isolated accessory nerve palsy. Follow-up MRI
      showed that the VA aneurysm gradually decreased in size over a period of several
      months. At the same time, her symptoms disappeared completely. CONCLUSION: We
      should keep in mind that isolated accessory nerve palsy can be caused by a large
      or giant vertebral aneurysm.

PMID- 24019787
TI  - Levodopa-responsive benign tremulous parkinsonism.
AB  - BACKGROUND: Benign tremulous parkinsonism (BTP) is a tremor dominant syndrome
      characterized by mild, levodopa-resistant parkinsonism with limited disability or
      progression. CASE PRESENTATION: A 56-year-old woman presented with a 2-year
      history of tremor. Neurological examination revealed right-hand rest tremor and
      slow finger tapping with decreased amplitude; however, we did not observe posture
      tremor, rigidity, bradykinesia, or posture disability. She was diagnosed with
      Parkinson's disease (PD) and received levodopa/carbidopa, effectively treating
      her rest tremor. At the age of 61 years, reoccurrence of the rest tremor was
      successfully treated again with levodopa/carbidopa and selegiline. Approximately
      11 years have passed since symptom onset and the patient shows no further disease
      progression. CONCLUSION: This case broadens the characterization of BTP to
      include levodopa-responsive PD.

PMID- 24019789
TI  - A case of expansion of traumatic choroidal rupture with delayed-developed outer
      retinal changes.
AB  - BACKGROUND: This study aims to report the expansion of a choroidal rupture site
      caused by blunt ocular trauma using scanning laser ophthalmoscope-optical
      coherence tomography. CASE REPORT: The clinical course of a 15-year-old girl with
      a traumatic ocular injury after being hit in the eye by an elbow was evaluated.
      Upon the first examination, the best-corrected visual acuity was 16/20. The
      findings were subretinal pigment epithelial hemorrhage and vertical choroidal
      rupture. Three weeks after the trauma, the patient's visual acuity was reduced to
      counting fingers at 30 cm. On fundus examination and fluorescein angiography
      subretinal pigment epithelial hemorrhage decreased, while the choroidal rupture
      expanded; on optical coherence tomography outer retinal changes in the adjacent
      area were detected. DISCUSSION: This study reveals that the delayed expansion of
      a choroidal rupture site and the delayed change of the adjacent outer retina
      improved.

PMID- 24019788
TI  - Intravitreal Injection of Dexamethasone Implant in Serous Macular Detachment
      Associated with Waldenstrom's Disease.
AB  - PURPOSE: To evaluate the efficacy of one intravitreal injection of dexamethasone
      (Ozurdex((r)); Allergan, Inc., Irvine, Calif., USA) in serous macular detachment
      (SMD) of one eye, associated with bilateral central retinal vein occlusion (CRVO)
      in a patient affected by Waldenstrom's macroglobulinemia (WM). PATIENTS AND
      METHODS: A female patient, affected by WM, complained of a progressive decrease
      in visual acuity, mainly in the left eye (LE). SMD in the LE associated with
      bilateral CRVO was diagnosed. One intravitreal injection of dexamethasone was
      administered in the LE and the patient was tested 1, 2, and 6 months after the
      injection. RESULTS: 1, 2, and 6 months after the injection, the spectral domain
      optical coherence tomography (SD-OCT) showed a progressive slight reduction of
      foveal thickness that was not related to any improvement of visual function.
      CONCLUSIONS: Treatment with dexamethasone (Ozurdex) induced a progressive slight
      reduction of SMD but no improvement of visual acuity, and it is possible that
      this is related to the condition of hematic hyperviscosity that is present in WM.

PMID- 24019790
TI  - Corneal confocal microscopy anomalies associated with cowden syndrome: a case
      report.
AB  - PURPOSE: To describe bilateral corneal alterations through confocal microscopy in
      a patient affected by Cowden syndrome (CS). METHODS: Evaluation of Schirmer's,
      fluorescein, and lissamine green dye tests. Confocal microscopy was performed in
      both eyes to investigate corneal abnormalities. RESULTS: Slit lamp observation
      showed the focal involvement of anterior stromal and epithelial layers.
      Schirmer's, fluorescein, and lissamine green dye test results were regular, while
      corneal confocal examination confirmed the disorganization of anterior stromal
      and epithelial layers in both eyes. CONCLUSION: CS is a rare autosomal-dominant
      systemic disorder. In our case, confocal analysis revealed predominance of
      alterations in the anterior stromal corneal layer, showing an increase of
      reflectivity, and a totally unstructured architecture in the epithelium layer.
      Even though the main purpose remains the prevention and the early diagnosis of
      different systemic tumors that could occur in affected patients, corneal confocal
      evaluation could play an important role in the early diagnosis of this rare
      disease.

PMID- 24019791
TI  - Rare and unusual choroidal abnormalities in a patient with systemic lupus
      erythematosus.
AB  - PURPOSE: To report a case of rare and unusual choroidal abnormalities in a 42
      year-old woman with systemic lupus erythematosus (SLE). METHODS: Images were
      obtained using fundus photography, fluorescein angiography, near-infrared
      reflectance (NIR) imaging, and optical coherence tomography (OCT). RESULTS: The
      patient had a history of SLE and central retinal artery occlusion in her right
      eye. Fundus examination showed no specific retinochoroidal abnormalities, with
      the exception of optic disc atrophy in her right eye and a peripapillary small
      hemorrhage in her left eye. However, NIR revealed multiple bright patchy lesions
      in the choroid of the posterior pole and the mid-periphery of the fundus in both
      eyes. OCT demonstrated irregular hyperreflectivity at the lesion sites.
      CONCLUSIONS: The observed choroidal abnormalities are highly specific findings
      and therefore indicative of neurofibromatosis type 1 (NF1). Since the coexistence
      of SLE and NF1 is extremely rare, this case provided the chance to examine the
      relationship between SLE and NF1.

PMID- 24019792
TI  - Retinal arterial occlusive disease in a young patient with cat scratch disease.
AB  - PURPOSE: To report an unusual case of a branch retinal arterial occlusion and
      bilateral multifocal retinitis in a young woman with cat scratch disease.
      METHODS: A 23-year-old woman was referred to our clinic complaining of a sudden
      scotoma in the upper part of the visual field of her left eye. Fundoscopy
      revealed occlusion of an inferior temporal branch of the retinal artery in the
      left eye and bilateral multifocal retinitis, which was confirmed by fluorescein
      angiography. Subsequent indocyanine angiography did not reveal choroidal
      involvement. Laboratory analysis showed rising IgG titers for Bartonella
      henselae. RESULTS: Cat scratch disease was diagnosed, and a 4-week course of
      doxycycline was initiated. The patient responded well to the antibiotics. Both
      retinitis and arterial occlusion were resolved, the visual field was regained and
      the patient reported elimination of her symptoms. CONCLUSIONS: Cat scratch
      disease should be considered in the differential diagnosis in young patients with
      retinal occlusive disease.

PMID- 24019793
TI  - Orbital inflammation developing from epidemic keratoconjunctivitis in an adult.
AB  - INTRODUCTION: We report a rare case of epidemic keratoconjunctivitis (EKC) that
      developed into an orbital inflammation in an adult. CASE PRESENTATION: A 67-year
      old Korean man, who had been diagnosed with EKC and treated for conjunctival
      injection and chemosis in the right eye for 4 days, was referred to Oculoplastics
      as orbital cellulitis was suspected. At the point of referral, clinical features
      such as decreased visual acuity, severe eyelid swelling, chemosis, follicles,
      corneal edema, limitations in lateral eye movement, and diplopia were observed in
      the right eye. Orbital cellulitis was suspected according to orbital computed
      tomography scan images, but there was no response to systemic antibiotics.
      Systemic steroid was administered instead, and then his symptoms and signs
      started to improve. The final diagnosis of this patient was orbital inflammation
      related to EKC based on the facts that there was no response to antibiotics, that
      he presented with contralateral symptoms and signs, that pseudomembrane formation
      occurred in both eyes, and that the symptoms resolved completely after 2 weeks.
      CONCLUSION: Clinicians need to consider the possibility of orbital inflammation
      developing from EKC, even in an adult patient, and treat the patient properly if
      the EKC symptoms and signs, such as conjunctival injection and follicles, are
      accompanied with symptoms and signs similar to orbital cellulitis.

PMID- 24019794
TI  - An insight into salivary markers in oral cancer.
AB  - Salivary diagnostics has fascinated many researcheres and has been tested as a
      valuable tool in the diagnosis of many systemic conditions and for drug
      monitoring. Advances in the field of molecular biology, salivary genomics and
      proteomics have led to the discovery of new molecular markers for oral cancer
      diagnosis, therapeutics and prognosis. Oral cancer is a potentially fatal disease
      and the outcome of the treatment and prognosis largely depends on early
      diagnosis. Abnormal cellular products elucidated from malignant cells can be
      detected and measured in various body fluids including saliva and constitute
      tumor markers. This article discusses the various salivary tumor markers and
      their role in oral pre-cancer and cancer. 

PMID- 24019795
TI  - Black triangle dilemma and its management in esthetic dentistry.
AB  - In recent years, clinician and dentist's esthetic demand in dentistry have
      increased rapidly, driven by an enhanced awareness of beauty and esthetics. The
      ultimate goal in modern restorative dentistry is to achieve "white" and "pink"
      esthetics in esthetically important zones. "White esthetics" is the natural
      dentition or the restoration of dental hard tissues with suitable materials.
      "Pink esthetics" refers to the surrounding soft-tissues, which includes the
      interdental papilla and gingiva that can enhance or diminish the esthetic result.
      Reconstruction of the lost interdental papilla is one of the most challenging and
      least predictable problems. Restoration and maintenance of these tissues with
      adequate surgical and prosthetic techniques are a real challenge in modern
      esthetic dentistry. Treatment of marginal tissue recession, excessive gingival
      display, deficient ridges, ridge collapse, and esthetic defects around teeth and
      implants are some of the esthetic problems associated with the interdental
      papilla that have to be corrected in todays scenario which has been discussed in
      this review. 

PMID- 24019796
TI  - Probiotics in dentistry: A boon or sham.
AB  - Probiotics are dietary supplements, which have been advocated for the prevention
      and the treatment of a wide range of diseases. These products consist of
      beneficial micro-organisms, which stimulate health promoting flora thus,
      suppressing the pathologic colonization and disease spread. Since, probiotics are
      now widely used in both medical (such as cancer risk reduction, gastrointestinal
      tract health, and urinary tract health) and dental specialties (reduction in
      caries development, in achieving periodontal health, reducing oral malodor,
      etc.), a thorough understanding of their risks and benefits are essential. This
      review focuses on the recent trends in use of probiotics in dentistry as well as
      the potential risks associated with them. 

PMID- 24019797
TI  - Oral splint for temporomandibular joint disorders with revolutionary fluid
      system.
AB  - Temporomandibular joint (TMJ) diseases and disorders refer to a complex and
      poorly understood set of conditions, manifested by pain in the area of the jaw
      and associated muscles and limitations in the ability to make the normal
      movements of speech, facial expression, eating, chewing, and swallowing. The
      conventional soft occlusal splint therapy is a much safer and effective mode of a
      conservative line of therapy in comparison to the surgical therapy for
      temporomandibular joint disorders (TMD). The purpose of this article is to review
      the AqualizerTM, an hydrostatic oral splint, as accurate, effective treatment and
      differential diagnostic tool in TMD that allow treating the patient's pain
      quickly and accurately saving valuable treatment time. The review article has
      been prepared doing a literature review from the world-wide web and
      pubmed/medline. 

PMID- 24019798
TI  - Efficacy of miswak on oral pathogens.
AB  - The oral cavity harbors a diverse and abundant number of complex oral pathogens
      causing different oral diseases. The development of dental caries and periodontal
      diseases has been found to be closely associated with various gram positive and
      gram negative microrganisms. Miswak, a natural toothbrush, has been documented as
      a potent antibacterial aid and its use is encouraged in different countries
      because of its good taste, texture, availability, cost and beneficial effect on
      teeth and supporting tissues. Different researches have been carried out to
      evaluate the antimicrobial effects of Miswak. This review encompasses the
      efficacy of Miswak on suppression of oral pathogens with respect to conducted on
      fungi as well as cariogenic, periodontal and endodontic bacteria. 

PMID- 24019799
TI  - Immunohistochemical analysis of syndecan-1 in leukoplakia and oral submucous
      fibrosis.
AB  - BACKGROUND: Syndecan-1 is abundant in normal tissues and reduced in squamous cell
      carcinomas. Leukoplakia and oral submucous fibrosis (OSF) are oral pre-cancerous
      disorders that have potential for malignant transformation. The aim of this study
      was to evaluate the expression of syndecan-1 in leukoplakia and OSF and to
      identify its role as a reliable marker for predicting malignant changes.
      MATERIALS AND METHODS: Expression of syndecan-1 was examined
      immunohistochemically in 42 cases of oral leukoplakia with or without epithelial
      dysplasia, 28 cases of OSF and 10 cases of normal oral epithelia as control. Mann
      Whiteny 'U' test was used for statistical analysis and the level of significance
      was fixed at P < 0.05. RESULTS: Intense syndecan-1 expression was observed in
      nine cases with normal epithelium. Immunopositivity was lost gradually as the
      extent of epithelial dysplasia increased. The significant reduction in syndecan-1
      expression was observed in leukoplakia as epithelial dysplasia progressed from
      moderate or severe. Similarly, significant reduction was observed in staining
      intensities in OSF with dysplasia. CONCLUSION: The results reveal that down
      regulation of syndecan-1 expression is associated with dysplastic changes in
      leukoplakia and OSF. Thus syndecan-1 can be considered as marker for predicting
      malignant changes.

PMID- 24019800
TI  - Effect of acid pre-conditioning and/or delayed light irradiation on enamel bond
      strength of three resin-modified glass ionomers.
AB  - BACKGROUND: Polymerization of resin-modified glass-ionomers (RMGIs) is mediated
      through two competing mechanisms: An acid-base reaction and a light-dependent
      resin polymerization. Furthermore, pre-conditioning with acid has resulted in an
      increase in enamel bond strength of some RMGIs. This in vitro study evaluated the
      effect of pre-conditioning and/or delayed irradiation on bond strength of three
      RMGIs to enamel. MATERIALS AND METHODS: In this in vitro study, 144 flat enamel
      surfaces of human molars were ground using consecutively finer abrasives up to
      600-grit silicon carbide paper. Each surface was rinsed and gently air-dried (n
      =12). The RMGIs (Fuji II LC Improved; Ionolux and Vitremer) were bonded to enamel
      surfaces using the following protocols: Groups 1: Based on manufacturers'
      instructions; Groups 2: Pre-conditioning with phosphoric acid for 30 s; groups 3:
      A 2-min delay in irradiation; groups 4: Pre-conditioning with acid for 30 s plus
      a 2-min delay in light activation. After 24-h storage at 37 degrees C and 500
      rounds of thermocycling, the samples underwent shear bond strength (SBS) test.
      Data was analyzed with 3-way ANOVA and Tukey HSD test (alpha =0.05). RESULTS:
      There were significant differences between the study groups (P < 0.001). Acid-pre
      conditioning increased Fuji II LC SBS values; it significantly decreased SBS
      values of Vitremer but had no effect on SBS values of Ionolux. Ionolux and
      Vitremer exhibited decreased enamel bond strength after a delay in light
      activation (P < 0.05). A 2-min delay in light activation combined with acid pre
      conditioning increased RMGI SBS values only for Fuji II LC. CONCLUSION: Within
      the limitations of the present study, the effect of acid pre-conditioning,
      delaying irradiation and both on enamel bond strength of RMGIs was material
      dependent. Further investigations are recommended.

PMID- 24019801
TI  - Effect of tramadol at different doses on orthodontic tooth movement and bone
      resorption in rats.
AB  - BACKGROUND: Tramadol is an opioid agonist that has the potential of being abused.
      The aim of this study was to compare the effect of different doses of tramadol on
      orthodontic tooth movement (OTM) and bone resorption in rats. MATERIALS AND
      METHODS: Forty-two male rats were assigned randomly to two experimental groups
      and one control group. Nickel-titanium coil springs were used to exert
      orthodontic force. The rats in the control group and experimental group-1,
      respectively, received a daily injection of 0.1 ml of normal saline and 10 mg/kg
      of tramadol for 14 days. The rats in experimental group-2 received 10 mg/kg of
      the same drug on days 1-4, 20 mg/kg on days 5-8, 40 mg/kg on days 9-12 and 60
      mg/kg on days 13 and 14. OTM was measured on days 4, 8, 12, and 14. At the end of
      the experimental period, the rats were sacrificed. Histological analysis was also
      performed to evaluate the number of osteoclasts, osteoblasts, and Howship's
      lacunae. RESULTS: Statistical analysis with analysis of variance tests showed
      that the rats in experimental group-2 had significantly decreased OTM compared
      with the other two groups (P < 0.05), whereas OTM for the rats in experimental
      group-1 was comparable to that in the control group (P > 0.05). The histological
      evaluations did not show any significant difference among the groups (P > 0.05).
      CONCLUSION: The effect of tramadol hydrochloride on OTM depends on the dosage
      used. High doses of the drug reduce the extent of OTM significantly.

PMID- 24019802
TI  - Total sialic acid, total protein and total sugar levels in serum and saliva of
      oral squamous cell carcinoma patients: A case control study.
AB  - BACKGROUND: Detection of cancer at an early stage is of utmost importance to
      decrease the morbidity and mortality of the disease. Apart from the conventional
      biopsy, non-invasive methods like analysis of serum and saliva may provide cost
      effective approach for screening a large population. Tumor markers are a major
      part of secondary prevention and thus, the detection of malignancies. The aim of
      this study was to evaluate total sialic acid (TSA), total protein and total sugar
      (TS) in serum and saliva of oral squamous cell carcinoma (OSCC) and controls to
      assess their role as a diagnostic marker. MATERIALS AND METHODS: Unstimulated
      whole saliva and sera were collected from 40 squamous cell carcinoma patients and
      20 controls. Serum and salivary TSA, total protein and TS estimation was carried
      out. This was correlated with clinical stages and histopathological grades of
      OSCC. The data obtained was analyzed statistically using Chi-square test, ANOVA
      and Student's t-test with SPSS statistical software. RESULTS: A highly
      significant rise in the salivary sialic acid, serum sialic acid and serum protein
      was noted in OSCC subjects compared to controls. Salivary protein, serum and
      salivary sugar did not show any significance. Furthermore, serum and salivary
      sialic acid levels were found to be significantly increased with increasing level
      of histopathological grading. CONCLUSION: The present study showed a significant
      increase in serum sialic acid, salivary sialic acid and serum protein from
      control to OSCC and suggests that these markers may be reliable in diagnosis and
      predicting prognosis.

PMID- 24019804
TI  - A comparative study on radiographic analysis of impacted third molars among three
      ethnic groups of patients attending AIMST Dental Institute, Malaysia.
AB  - BACKGROUND: The patterns of facial growth, jaw and tooth size are inherited and
      are likely to differ among population and races. Aim of this study is to evaluate
      and compare the pattern of third molar (3M) impaction among three different
      ethnic groups (Chinese, Indian, Malay) of patients attending AIMST Dental
      Institute, Malaysia. MATERIALS AND METHODS: Dental records and orthopantomographs
      of 2200 patients aged between 20 and 40 years were retrieved and examined
      retrospectively. Wherever impacted 3Ms were present, the status of 3Ms, their
      location, the level of impaction and angulations were recorded and analyzed using
      STATDISK (version 10.4) and the values obtained were compared with least square
      distance of 0.05 level. RESULTS: About 667 radiographs met with the inclusion
      criteria and showed the presence of 1008 impacted 3Ms. On overall comparison the
      incidence of level B impactions were found to be higher in our study. Level A
      impactions were frequently seen in Chinese (41.9%), level B in Indian (36.4%) and
      level C impactions had an equal distribution among Chinese and Malays (34.1%).
      The difference was highly significant (P >= 0.05). Mesioangular impaction (49.8%)
      followed by distoangular (22.9%) were the most common impactions among all the
      three races. CONCLUSION: On comparison, mesioangular impaction was found to be
      the most frequent among all the three races whereas differences were seen in
      levels of impaction to some extent among the ethnic groups. But as a limitation,
      our findings and results reflected the status of 3Ms of patients attending AIMST
      Dental Institute, not entire Malaysia. Therefore more similar studies have to be
      carried out in other parts of Malaysia to substantiate our present findings.

PMID- 24019803
TI  - Assessment of the effect of diode laser therapy on incisional wound healing and
      expression of iNOS and eNOS on rat oral tissue.
AB  - BACKGROUND: The aim of this study was to compare the effects of diode laser
      irradiation on wound healing in oral rat mucosa and also to measure the amount of
      inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on oral wound
      healing. Healing was assessed by histology and the amounts of eNOS and iNOS were
      measured by real-time polymerase chain reaction (PCR). MATERIALS AND METHODS:
      Twenty-four standardized incisions were carried out on the buccal mucosa of 12
      male Wistar rats; each rat received two incisions on the opposite sides of the
      buccal mucosa by using a steel scalpel. On the right side (test side), a diode
      laser (660 nm) was employed on the incision for 10 seconds on days 1-4 and 6-9.
      The left side (control side) did not receive any laser. Histological and real
      time PCR analysis were done on tissue samples after 2, 7, 14, and 21 days.
      RESULTS: Histological analysis showed that the tissue healing after seven days on
      the laser irradiated side was better than the control side, but there was no
      significant difference between the two sides on days 2, 14, and 21 after surgery.
      Paired t-test analysis showed that there was no significant difference in the
      amount of eNOS between the groups. The difference in the amounts of iNOS between
      the groups was significant; it was more in the laser-irradiated side than the
      control side. CONCLUSION: Histological findings showed that diode laser needs
      several repeated irradiations for the acceleration of wound healing. The iNOS
      amount showed that increases are associated with better healing.

PMID- 24019805
TI  - Evaluation of push-out bond strength of AH26 sealer using MTAD and combination of
      NaOCl and EDTA as final irrigation.
AB  - BACKGROUND: During endodontic procedures, the smear layer is formed as a result
      of mechanical instrumentation of the canal. Combination of ethylenediamine
      tetraacetic acid (EDTA) and sodium hypochlorite (NaOCl) is widely used for
      removal of the smear layer. Application of Mixture of tetracycline, acid, and
      detergent (MTAD) as final irrigant subsequent to initial irrigation of 1.35%
      NaOCl has been proposed to increase clinical efficiency, biocompatibility and
      prolonged intra-canal antibacterial activity. Considering the importance of
      adhesion of endodontic sealers to the dentin walls of a prepared root canal, the
      present study evaluated push-out bond strength of AH26 sealer using final
      irrigation of MTAD and EDTA + NaOCl. MATERIALS AND METHODS: Sixty five single
      rooted teeth were prepared endodontically with the same chemomechanical technique
      and were randomly divided into three groups based on their final irrigation
      regimen: 17% EDTA + 5.25% NaOCl group (n =30), MTAD group (n =30) and control
      group (n =5). Obturation of the canals was performed with gutta-percha and AH26
      sealer. All teeth were sectioned in order that two specimens of 1 mm thickness
      were obtained from the coronal and the middle one third of each root resulting in
      60 specimens for each experimental group and 10 specimens for control group. For
      push-out test, universal-testing machine was used to exert a constant compressive
      apico-coronal load at a speed of 0.5 mm/min. Minimum amount of compressive load
      caused dislodgement was measured and converted into megapascal (MPa) scale. One
      way analysis of variance and the post hoc Tukey test were used for statistical
      analysis of the data (alpha = 0.05). RESULTS: In MTAD group, mean micro-push-out
      bond strength of AH26 sealer to dentin walls was obtained 2.23 MPa compared to
      2.0 MPa for EDTA + NaOCl group. The mean bond strength of AH26 sealer to dentin
      walls was significantly greater using MTAD compared with combination of EDTA and
      NaOCl or saline. CONCLUSION: MTAD final rinse significantly increased micro-push
      out bond strength of AH26 sealer to canal dentin walls compared with EDTA +
      NaOCl.

PMID- 24019806
TI  - Comparative clinical and microbiological efficacy of mouthwashes containing 0.2%
      and 0.12% chlorhexidine.
AB  - BACKGROUND: The main stay of primary and secondary prevention of periodontal
      diseases has been the control of supra gingival plaque. Acceptable plaque control
      by mechanical means is difficult to achieve by most individuals, so mouth rinses
      represent one form of attack on oral microbes and the malodor. Chlorhexidine
      (CHX) is a broad-spectrum antimicrobial agent known to cause damage to the cell
      membrane of microorganisms and at higher concentrations causes precipitation and
      coagulation of the proteins in the cytoplasm of the exposed microbes. The aim of
      this study is to evaluate and compare the efficacy of 0.12% and 0.2%
      concentration of CHX gluconate clinically as well as microbiologically. MATERIALS
      AND METHODS: The single blind placebo controlled randomized study design
      comprising of 75 males with an age between 25 years and 50 years were selected
      from out-patient Department of Periodontics. The subjects were randomly divided
      into five groups. After baseline clinical and microbiological examination, the
      groups were subjected to mechanical plaque control with or without mouthwashes
      containing various concentrations of CHX and placebo. After 90 days the data
      pertaining to clinical and microbiological parameters were compared to the
      baseline data so as to compare the efficacy of different concentrations of
      mouthwashes. RESULTS: The results achieved with the use of 0.2% and 0.12%
      concentrations of CHX were comparable; taking into consideration of various
      clinical and microbiological parameters. CONCLUSION: The study recommends the use
      of low concentration of (0.12%) CHX for better patient compliance with the
      optimum clinical results.

PMID- 24019807
TI  - The effect of microwave/laboratory light source postcuring technique and wet
      aging on microhardness of composite resin.
AB  - BACKGROUND: Although composite restorations are really valuable for esthetic
      zones, they have shown less longevity rather than amalgam restorations. Since it
      may be related to the method used for curing the composite, postcuring could
      increase the degree of conversion and result in more long-lasting composite
      restorations. This study was planned to evaluate the effect of two different
      postcuring techniques on microhardness of indirect composite resin after wet
      aging and comparing them with the direct type. MATERIALS AND METHODS: In this
      experimental study, 99 composite disk-shaped (6.5 * 2.5 mm) specimens of
      composite (Gradia GC, Japan) were prepared in split mold. The indirect composite
      specimens were postcured by laboratory light source (Labolite LV-III GC Corp,
      Japan) or microwave unit (MC 2002 JR, LG, Korea). Then, the aging procedure was
      done for 24 h, 30 and 180 days in distilled water. The Vicker's Hardness test
      (VHN) on surface of specmens was measured by Wolpert microhardness tester and the
      data were analyzed by the two-way analysis of variance (ANOVA) and Tukey's post
      hoc tests. (P <= 0.05). RESULTS: The statistical analysis revealed that surface
      microhardness of postcured composite by microwave and laboratory light source was
      more than that of direct composite (P = 0.0001) and postcuring by microwave was
      more effective than postcuring by laboratory light source (P = 0.004). The 30
      days stored composite demonstrated significant decrease of VHN compared with the
      24-h stored samples (P = 0.0001), with a more significant VHN decrease after 180
      days of aging (P = 0.045). CONCLUSION: Postcuring increased the surface
      microhardness and aging reduced the surface microhardness of indirect composite.

PMID- 24019808
TI  - Beam hardening artifacts by dental implants: Comparison of cone-beam and 64-slice
      computed tomography scanners.
AB  - BACKGROUND: Cone beam computed tomography (CBCT) is an alternative to a computed
      tomography (CT) scan, which is appropriate for a wide range of
      craniomaxillofacial indications. The long-term use of metallic materials in
      dentistry means that artifacts caused by metallic restorations in the oral cavity
      should be taken into account when utilizing CBCT and CT scanners. The aim of this
      study was to quantitatively compare the beam hardening artifacts produced by
      dental implants between CBCT and a 64-Slice CT scanner. MATERIALS AND METHODS: In
      this descriptive study, an implant drilling model similar to the human mandible
      was used in the present study. The implants (Dentis) were placed in the canine,
      premolar and molar areas. Three series of scans were provided from the implant
      areas using Somatom Sensation 64-slice and NewTom VGi (CBCT) CT scanners.
      Identical images were evaluated by three radiologists. The artifacts in each
      image were determined based on pre-determined criteria. Kruskal-Wallis test was
      used to compare mean values; Mann-Whitney U test was used for two-by-two
      comparisons when there was a statistical significance (P < 0.05). RESULTS: The
      images of the two scanners had similar resolutions in axial sections (P = 0.299).
      In coronal sections, there were significant differences in the resolutions of the
      images produced by the two scanners (P < 0.001), with a higher resolution in the
      images produced by NewTom VGi scanner. On the whole, there were significant
      differences between the resolutions of the images produced by the two CT scanners
      (P < 0.001), with higher resolution in the images produced by NewTom VGi scanner
      in comparison to those of Somatom Sensation. CONCLUSION: Given the high quality
      of the images produced by NewTom VGi and the lower costs in comparison to CT, the
      use of the images of this scanner in dental procedures is recommended, especially
      in patients with extensive restorations, multiple prostheses and previous
      implants.

PMID- 24019809
TI  - Fibrin clot adhesion to root surface treated with tetracycline hydrochloride and
      ethylenediaminetetraacetic acid: A scanning electron microscopic study.
AB  - BACKGROUND: Connective tissue attachment following periodontal regenerative
      surgery is directly related to the attachment of fibrin clot on to the root
      surface during early wound healing events. The adhesion of fibrin clot to the
      root surface affected by periodontal disease depends on the biologic acceptance
      of the root surface which can be accomplished by various root conditioning
      procedures during periodontal therapy. The present in vitro study has been
      designed to evaluate and compare the degree of fibrin clot adhesion to root
      surfaces treated with root conditioning agents tetracycline hydrochloride and
      ethylenediaminetetraacetic acid (EDTA). MATERIALS AND METHODS: A total of 30
      dentin blocks are divided into three groups and treated with tetracycline
      hydrochloride, EDTA and phosphate buffered saline and a drop of blood is added to
      each dentin block. The dentin blocks are then prepared for scanning electron
      microscopic analysis and examined for the degree of fibrin network frmation and
      entrapped erythrocytes. RESULTS: The degree of fibrin clot adhesion was highest
      with tetracycline hydrochloride group, then with control group and least with
      EDTA treated group. CONCLUSION: According to the results of the present study,
      root conditioning with tetracycline hydrochloride produces a biologically
      acceptable root surface with enhanced fibrin clot adhesion, which is a critical
      step in early wound healing process. EDTA gel appears less effective in producing
      a root surface necessary for the adhesion of fibrin clot. The control without any
      root conditioning procedure showed poor fibrin clot adhesion when compared to
      tetracycline treated group, but when compared to EDTA treated group the fibrin
      clot adhesion was slightly better.

PMID- 24019811
TI  - Scurvy-scorbutic siderosis of gingiva: A diagnostic challenge - A rare case
      report.
AB  - This case reports a rare condition of scurvy which posed a diagnostic difficulty.
      However, a thorough medical and diet history, along with clinical and
      histopathological examination aided in prompt diagnosis and successful management
      of the case. Occurrence of scurvy in today's contemporary society is said to be
      rare. Lack of fresh fruits and vegetables in the diet can lead to this condition.
      Diagnosis may be difficult due to its rarity and presence of non specific
      symptoms, which may pose a challenge to the clinician. A comprehensive history,
      clinical examination along with clinical and histopathological features led to
      arrive at a proper diagnosis. Local procedures and systemic therapy aided in the
      successful management of the case. A marked improvement in the gingival status
      and in the physical well being of the patient resulted after treatment. This case
      report describes the various manifestations of scurvy that posed a diagnostic
      challenge to the clinician. This condition which can be fatal if untreated can be
      easily prevented with inclusion of healthy food in the diet and modification in
      the lifestyle. 

PMID- 24019810
TI  - Comparison of glycosylated hemoglobin (HbA1C) levels in patients with chronic
      periodontitis and healthy controls.
AB  - BACKGROUND: The aim of this study was to determine if glycosylated hemoglobin is
      elevated in patients with chronic periodontitis who have not been diagnosed with
      diabetes and also to compare the HbA1c levels that were obtained with lab and
      chairside test kit. MATERIALS AND METHODS: A Case control study was designed.
      Glycosylated hemoglobin (HbA1c) was assessed using a chairside kit and laboratory
      method in 70 subjects without diabetes but with chronic periodontitis [having at
      least 10 teeth (at least one site around each tooth) with probing depth (PD) >= 5
      mm, bleeding on probing (BOP) >=15% and clinical attachment level (CAL) >= 1 mm]
      and 70 healthy controls (PD <= 4 mm and BOP <= 15%). Groups were compared using
      the t-test and multiple linear regression model analysis. Karl Pearson's
      correlation coefficient was used to compare the relationship between different
      variables. RESULTS: In this case control study HbA1c (Lab and Kit) were slightly
      higher and statistically significant in chronic periodontitis cases than in
      healthy controls. CONCLUSION: Chronic periodontitis is associated with a slight
      elevation in glycosylated hemoglobin (lab and chair side kit) and that the
      clinical significance of this difference remains to be determined. This
      preliminary finding is consistent with earlier reports that chronic periodontitis
      is associated with elevated blood glucose in adults without diabetes and may
      increase one's risk for type-2 diabetes.

PMID- 24019812
TI  - Submental intubation.
AB  - MacInnis and Baig modified Altemirs' original technique for sub-mental
      intubation. Instead of a lateral entry, they described a central entry just
      anterior to the sub-mental crease that does not carry the risk of damage to the
      lingual nerves, submandibular ducts and sublingual glands. We describe here our
      experience with this modified sub-mental intubation that also allows the
      operating surgeon to provide for a correct midline and optimal esthetics in case
      of panfacial trauma. 

PMID- 24019813
TI  - Oral malignant melanoma: A case report of an unusual clinical and histologic
      presentation.
AB  - Malignant melanoma is a potentially aggressive tumor of melanocytic origin.
      Primary oral malignant melanoma is a rare neoplasm, accounting for 0.5% of all
      oral malignancies. The present case occurred in a 60-year-old female patient, as
      a pedunculated growth involving the palate and alveolar ridge and histologically
      showing a desmoplastic differentiation. The article discusses the distinct
      clinico-pathologic presentation of this case and emphasizes on the need to
      identify and report such cases for further understanding of their biologic
      behavior. 

PMID- 24019814
TI  - Extracted wisdom teeth: Preserve or discard???

PMID- 24019815
TI  - Oral health during pregnancy: A study from women with pregnancy.

PMID- 24019816
TI  - Protective effects of the Morus alba L. leaf extracts on cisplatin-induced
      nephrotoxicity in rat.
AB  - Cisplatin (CP) as an important anti-tumor drug causes nephrotoxicity mainly by
      oxidative stress and renin-angiotensin system (RAS). Since flavonoids have high
      antioxidant activity and probable role in the inhibition of RAS, this study was
      designed to investigate the protective effect of hydroalcoholic extract and
      flavonoid fraction of Morus alba leaves on cisplatin-induced nephrotoxicity in
      rat. Extracts of Morus alba leaves were prepared and analyzed Phytochemically.
      Male rats (160-200 g) were used in this study (n=7-9). Normal group received 0.2
      ml normal saline intraperitoneally (i.p.) once daily for ten days. Control
      animals received CP on the third day and saline in the remaining days. Other
      groups received either hydroalcoholic extract (200, 400 and 600 mg/kg, i.p.) or
      flavonoid fraction (50, 100 and 200 mg/kg, i.p.) for two days before CP
      administration and thereafter until tenth day. Serum concentrations of blood urea
      nitrogen (BUN), creatinine (Cr) and nitric oxide were measured using standard
      methods. Also left kidneys were prepared for pathological study. The serum levels
      of BUN and Cr increased in animals received CP. Hydroalcoholic extract was
      ineffective in reversing these alterations but flavonoid fraction (50 and 100
      mg/kg) significantly inhibited CP-induced increases of BUN and Cr. None of the
      treatments could affect serum concentration of nitric oxide. Flavonoid fraction
      could also prevent CP-induced pathological damage of the kidney. It seems that
      concurrent use of flavonoid fraction of Morus alba with CP can protect kidneys
      from CP-induced nephrotoxicity. 

PMID- 24019817
TI  - The apoptotic effects of sirtuin1 inhibitor on the MCF-7 and MRC-5 cell lines.
AB  - Sirtuin1 (SIRT1) is an enzyme that deacetylates histones and several nonhistone
      proteins including p53 during stress and plays an important role in the survival
      of tumor cells. Hereby, this study describes the potency of salermide as a SIRT1
      inhibitor to induce apoptosis in the MCF-7 and MRC-5 cell lines. MCF7 and MRC-5
      cell lines were cultured in RPMI-1640 and treated with or without salermide at
      concentration of 80.56 MUmol/L, based on the half-maximal inhibitory
      concentration (IC50) index at different times (24, 48 and72 h). The IC50 value
      was established for the salermide in MCF-7. The percentage of apoptotic cells was
      measured by flow cytometry. Real-time quantitative RT-PCR was performed to
      estimate the mRNA expression of sirtuin1 in MCF-7 and MRC-5 with salermide at
      different times. ELISA and Bradford protein techniques were used to detect
      endogenous levels of total and acetylated p53 protein generated in MCF-7 and MRC
      5 cells. Our findings indicated that salermide can induce apoptosis in MCF-7
      significantly more effective than MRC-5 cells. We showed that the expression of
      SIRT1 was dramatically down-regulated by increasing the time of salermide
      treatment in MCF-7 but not MRC-5 and that the acetylated and total p53 protein
      levels were increased more in MCF-7 than MRC-5. Salermide, by decreasing the
      expression of sirtuin1 gene, can induce acetylation of P53 protein and
      consequently induce significant cell death in MCF-7 that was well tolerated in
      MRC-5. 

PMID- 24019818
TI  - Evaluation of anticonvulsant effect of two novels 4-[1-(4-fluorobenzyl)- 5
      imidazolyl] dihydropyridine derivatives in mice.
AB  - In this study the anticonvulsant effect of two dihydropyridine derivatives
      [diethyl -1,4- dihydro -2,6-dimethyl -4-(4- fluoro benzyl-2- methylthio -5-
      imidazolyl)-3,5- pyridine dicarboxilat (A) and diethyl -1,4-dihydro -2,6- diethyl
      -4-(4- fluoro benzyl-2- methylthio -5- imidazolyl)-3,5- pyridine dicarboxilat
      (B)] by pentylenetetrazole (PTZ) and electroshock in mice was evaluated. The
      latency and HLTE (hind limb tonic extensions), the duration of HLTE and the
      mortality protection in pentylenetetrazole test and the HLTE duration in
      electroshock test were assessed. Both compounds had significant differences with
      negative control in all doses used. There was no significant difference between
      nifedipine and B (96.7 and 169.2 mg/kg doses) in the starting point of HLTE and
      between nifedipine andA(62.2 and 108.9 mg/kg doses) in the duration of HLTE in
      the PTZ test. Also, there was no significant difference between nifedipine and B
      (96.7 and 169.2 mg/kg doses) andA(62.2 and 108.9 mg/kg doses) in electroshock
      test. All doses ofAand B and nifedipine showed less effect than phenytoin and
      valproate. This study showed that bothAand B have anticonvulsant activity in the
      PTZ-induced seizure model and the MES test. These compounds, thus, might be
      useful in the petit mal and grand mal epilepsy. 

PMID- 24019819
TI  - Quantitative structure activities relationships of some 2-mercaptoimidazoles as
      CCR2 inhibitors using genetic algorithm-artificial neural networks.
AB  - Quantitative relationships between structures of twenty six of 2
      mercaptoimidazoles as C-C chemokine receptor type 2 (CCR2) inhibitors were
      assessed. Modeling of the biological activities of compounds of interest as a
      function of molecular structures was established by means of genetic algorithm
      multivariate linear regression (GA-MLR) and genetic algorithm (GA-ANN). The
      results showed that, the pIC50 values calculated by GA-ANN are in good agreement
      with the experimental data, and the performance of the artificial neural networks
      regression model is superior to the multivariate linear regression-based (MLR)
      model. With respect to the obtained results, it can be deduced that there is a
      non-linear relationship between the pIC50 s and the calculated structural
      descriptors of the 2-mercaptoimidazoles. The obtained models were able to
      describe about 78% and 93% of the variance in the experimental activity of
      molecules in training set, respectively. The study provided a novel and effective
      approach for predicting biological activities of 2-mercaptoimidazole derivatives
      as CCR2 inhibitors and disclosed that combined genetic algorithm and GA-ANN can
      be used as a powerful chemometric tools for quantitative structure activity
      relationship (QSAR) studies. 

PMID- 24019820
TI  - Screening for antimalarial and acetylcholinesterase inhibitory activities of some
      Iranian seaweeds.
AB  - Alcoholic extracts of 8 different types of seaweeds from Iran's Persian Gulf were
      tested for their antimalarial and acetylcholinesterase enzyme (AChE) inhibitory
      activities for the first time. A modified Ellman and Ingkaninan method was used
      for measuring AChE inhibitory activity in which galanthamine was used as the
      reference. The antimalarial assay was performed using microculture radioisotope
      technique. Mefloquine and dihydroartemisinin were uased as the standards. The
      extract of Sargassum boveanum (Sargasseae family) showed the highest AChE
      inhibitory activity (IC50 equals to 1 mg ml(-1)) while Cystoseira indica
      (Cystoseiraceae family) exhibited the least activity (IC50 of 11 mg ml(-1)). The
      species from Rhodophyta (Gracilaria corticata and Gracilaria salicornia) also
      showed moderate activities (IC509.5, 8.7 mg ml(-1), respectively). All extracts
      were inactive in antimalarial assay. 

PMID- 24019821
TI  - Myocardial capillary density in normal and diabetic male rats: Effect of
      bezafibrate.
AB  - Cardiovascular disease is the common cause of mortality in diabetic subjects.
      Recently, it is indicated that peroxisome proliferator-activated receptors
      (PPARs) agonists have beneficial effect on cardiovascular system especially on
      angiogenesis. PPARs have three isotypes: PPARalpha, PPARbeta/delta and PPARgamma.
      In this study, we evaluated the effect of bezafibrate as pan PPAR agonist on
      myocardial capillary density in type I diabetic rats. Eighteen male wistar rats
      were randomly divided into three groups (n=6 each): control, diabetic and
      diabetic+bezafibrate (400 mg/kg/day) by gavage every day. Diabetes was induced by
      a single dose of streptozotocin (55 mg/kg), intraperitoneally. After 21 days,
      capillary density in the myocardial tissue was evaluated by immunohistochemical
      staining and reported as capillaries per mm(2). Blood samples were taken before
      and after the experiment. Diabetes was associated by lower serum nitric oxide
      (NO) concentration and reduced myocardial capillary density compared to control
      group (121.71 +/- 13.32 vs. 158.78 +/- 11.08 /mm(2); P<0.05). Administration of
      bezafibrate significantly increased serum NO level and improved angiogenesis in
      myocardial tissue of diabetic animals (170.24 +/- 15.76 vs.121.71 +/- 13.32
      /mm(2); P<0.05). There was a positive correlation between serum NO concentration
      and myocardial capillary density (r=0.90). Activation of all isotypes of PPAR by
      bezafibrate improves heart capillary density in diabetic animals and it seems
      that it can be considered for treatment or prevention of coronary heart disease
      in diabetic subjects. 

PMID- 24019822
TI  - Development and characterization of controlled release polar lipid microparticles
      of candesartan cilexetil by solid dispersion.
AB  - Candesartan cilexetil (CC) is a newer class of angiotensin II receptor antagonist
      used for the treatment of hypertension. The solubility of the CC is very poor and
      its oral bioavailability is only 15%. The controlledrelease polar lipid
      microparticles of CC (formulations F1, F2, F3 and F4) were prepared using
      variable erodible lipophilic excipients like hydrogenated castor oil, stearic
      acid, cetostearyl alcohol and carnauba wax by fusion method. The particle sizes
      of polar lipid microparticles were less than 50 microns and they were irregular
      in shape. Drug content ranged between 98.96 +/- 2.1 and 101.9 +/- 1.6% were
      present in all the formulations. The formulation F3 showed better drug release
      throughout the study period in a controlled release manner. Moreover, the in
      vitro release showed that all the formulations were best fitted to Higuchi model.
      Accelerated stability studies indicated that there was no significant changes in
      the chemical and physical characteristics of the formulated drug product during
      initial and at the end of the study period. The FTIR and DSC studies showed that
      there was no interaction between the drug and lipophilic excipients and no
      polymorphic transitions in all formulations. The X-ray diffraction peak of solid
      dispersion indicated that the crystalline nature of CC disappeared and no new
      peaks could be observed, suggesting the absence of interaction between drug and
      excipients. 

PMID- 24019823
TI  - Antispasmodic effects of Prangos ferulacea acetone extract and its main component
      osthole on ileum contraction.
AB  - Prangos ferulacea is a plant found in the Mediterranean and Middle-east regions
      used as carminative, anti-flatulent, emollient and antibacterial herb. It is
      believed that the coumarins are responsible for some of known effects of Prangos.
      In this research the relaxant effects of P. ferulacea coumrin rich extract as
      well as osthole as its main prenylated coumarins were investigated on rat ileum
      contraction in vitro. Relaxant effect of osthole and P. ferulacea extract were
      examined on contraction induced by KCl, acetylcholine (ACh) and electrical field
      stimulation (EFS) and compared with propantheline and nifedipine. The acetone
      extract of P. ferulacea concentration-dependently relaxed ileum contraction
      induced by KCl (IC50=1.3 +/- 0.25 MUg/ml), ACh (IC50=7.7 +/- 1.1 MUg/ml) and EFS
      (IC50=8.8 +/- 1.4 MUg/ml), while, the extract at lower concentration (4 MUg/ml)
      potentiated the ACh and EFS responses. Unlike the extract, osthole did not
      potentiate the ileum contraction but concentration-dependently inhibited ileum
      contractile responses to KCl (IC50=2.2 +/- 0.7 MUg/ml), ACh (IC50=2.5 +/- 0.7
      MUg/ml) and EFS (IC50=2.8 +/- 0.24 MUg/ml). Propantheline concentration
      dependently inhibited the ileum response to ACh, with IC50 value of 0.61 +/-
      0.09nM without affecting the KCl response. As expected, the EFS response was only
      partially reduced. Nifedipine (0.2-50 nM) inhibited tonic contraction induced by
      KCl with IC50 value of 2.5 +/- 0.8 nM but only partially inhibited the response
      to ACh. However, the response to EFS was reduced only by 33%. These results
      confirmed both potentiatory and inhibitory action of P. ferulacea extract on rat
      ileum contractile activity. Osthole is responsible for the inhibitory effect but
      potentiating components are not yet known. 

PMID- 24019824
TI  - Metalloid compounds as drugs.
AB  - The six elements commonly known as metalloids are boron, silicon, germanium,
      arsenic, antimony, and tellurium. Metalloid containing compounds have been used
      as antiprotozoal drugs. Boron-based drugs, the benzoxaboroles have been exploited
      as potential treatments for neglected tropical diseases. Arsenic has been used as
      a medicinal agent and arsphenamine was the main drug used to treat syphilis.
      Arsenic trioxide has been approved for the treatment of acute promyelocytic
      leukemia. Pentavalent antimonials have been the recommended drug for visceral
      leishmaniasis and cutaneous leishmaniasis. Tellurium (IV) compounds may have
      important roles in thiol redox biological activity in the human body, and
      ammonium trichloro (dioxoethylene-O, O'-)tellurate (AS101) may be a promising
      agent for the treatment of Parkinson's disease. Organosilicon compounds have been
      shown to be effective in vitro multidrug-resistance reverting agents. 

PMID- 24019825
TI  - The effects of chloroform, ethyl acetate and methanolic extracts of Brassica rapa
      L. on cell-mediated immune response in mice.
AB  - Turnips with a long history of usage, are helpful in preventing breast and
      prostate cancer, inflammation and body's immune system dysfunction. In this
      study, we investigated the effects of chloroform, ethyl acetate and methanolic
      extracts of Brassica rapa L. on cell-mediated immune response in mice.
      Chloroform, ethyl acetate and methanolic extracts of B. rapa glands were prepared
      by maceration method. To study the effects of B. rapa on acquired immunity,
      groups of Balb/c mice (n=8) were used. Sheep red blood cell (SRBC) was injected
      (s.c., 1*10(8)cells/ml, 0.02 ml) and 5 days later, different extracts (10, 100
      and 500 mg/kg), betamethasone (4 mg/kg) and Levamisol (4 mg/kg) as a positive
      control and normal saline as a negative control were given i.p. After 1 h SRBC
      was injected to footpad (s.c., 1*10(8)cells/ml, 0.02 ml) and footpad swelling was
      measured up to 72 h. To investigate the effects of B. rapa on innate immunity the
      same procedure was used, but animals only received one injection of SRBC 1 h
      after i.p. injection of test compounds. Our findings showed that SRBC induced an
      increase in paw swelling with maximum response at 6-8 and 2-4 h for innate and
      acquired immunity, respectively. Betamethasone inhibited and levamisol increased
      paw thickness in both models. In both innate and acquired immunity models,
      chloroform, ethyl acetate and methanolic extracts of B. rapa glands significantly
      and dose-dependently reduced paw thickness. Ethyl acetate extract showed better
      effect. As glucosinolates are better extracted by ethyl acetate, it may be
      concluded that they are contributed in the more pronounced effects of ethyl
      acetate extract. 

PMID- 24019826
TI  - Quantitative evaluation of DNMT3B promoter methylation in breast cancer patients
      using differential high resolution melting analysis.
AB  - DNA methylation plays an important role in carcinogenesis through epigenetic
      silencing of tumor suppressor genes. Aberrant methylation usually results from
      changes in the activity of DNA methyltransferases (DNMTs). Some studies show that
      the overexpression of the DNMTs may lead to aberrant methylation of tumor
      suppressor genes. Also the overexpression of DNMTs may be related to methylation
      status of their genes. Due to limited number of studies on DNMT3B promoter
      methylation, this study was performed to quantitatively measure the methylation
      level of DNMT3B gene in archival formalin fixed paraffin embedded (FFPE) tissues
      from breast cancer patients. Using differential high resolution melting analysis
      (D-HRMA) technology, the methylation level of DNMT3B gene promoter was quantified
      in 98 breast cancer FFPE tissues and also 10 fresh frozen normal tissue samples.
      Statistical analyses used for analyzing the correlation between the methylation
      and clinical variables. All the normal samples were found to be methylated at the
      DNMT3B promoter (the average methylation level 3.34%). Patients were identified
      as hypo-methylated (mean methylation level 0.8%), methylated (mean methylation
      level 2.48%) and hyper-methylated (mean methylation level 10.5%). Statistical
      analysis showed a significant correlation between the methylation status and the
      sample type, cancer type and tumor size. Also the methylation level was
      significantly associated with histologic grade. It is concluded that
      quantification of DNMT3B promoter methylation might be used as a reliable and
      sensitive diagnostic and prognostic tool in breast cancer. Also D-HRMA is
      demonstrated as a rapid and cost effective method for quantitative evaluation of
      promoter methylation. 

PMID- 24019827
TI  - Comparison of effect of intravenous ketamine, peritonsillar infiltration of
      tramadol and their combination on pediatric posttonsillectomy pain: A double
      blinded randomized placebo-controlled clinical trial.
AB  - In this study, the aim was the evaluation of effect of intravenous (IV)
      administration of ketamine, peritonsillar infiltration of tramadol and their
      combination for control of post-operative pain in comparison with single use of
      each drug in children undergoing tonsillectomy. One hundred and twenty children,
      aged 2- 15 years, selected for elective adenotonsillectomy were enrolled in the
      study. We divided the patients into four groups of 30 each, Group I: received IV
      ketamine 0.5 mg/kg, Group II: received peritonsillar infiltration of tramadol 2
      mg/kg, Group III: received IV ketamine 0.5 mg/kg added to peritonsillar tramadol
      2 mg/kg and Group IV: received IV and peritonsillar infiltration of 0.9% saline.
      We utilized the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS)
      recorded each 15 min after surgery to the first h and then each 2 , 4, 6, 8, 16,
      24 h to assess pain levels postoperatively. The analysis of data showed that
      Group III had significantly lower CHEOPS scores than another three groups
      (P<0.001), while both Groups I and II had the same ranged scores, which were not
      statistically significant (P>0.05). During 24 h after surgery, the first time for
      analgesic requirement was higher in Group III in comparison with other groups
      (P<0.001). Combined use of IV ketamine 0.5 mg/kg with peritonsillar infiltration
      of tramadol 2 mg/kg provided better and more prolong analgesic effects compared
      with using each drug alone in patients undergoing tonsillectomy. 

PMID- 24019828
TI  - Synthesis, analysis and cytotoxic evaluation of some hydroxypyridinone
      derivatives on HeLa and K562 cell lines.
AB  - A range of iron bidentae ligands containing the chelating moiety 3-
      hydroxypyridin-4-ones (HPOs) have been synthesized via a single or a three-step
      synthetic pathway. In the single-step reaction, maltol was directly reacted by
      suitable primary amine and in the second synthetic method; benzylated maltol was
      reacted with related amines to give 1-substuted-2-methyl-3-benzyloxypyridin-4-one
      derivatives. Finally, removal of the benzyl group under acidic conditions was
      performed by catalytic hydrogenation to yield the favored bidentate chelators as
      HCl salt. The partition coefficient of the free ligands and their iron (III)
      complexes between an aqueous phase buffered at pH 7.4 and 1-octanol were also
      determined. The cytotoxic effects of these iron chelators against HeLa and K562
      cell lines were evaluated using MTT assay and the results showed that
      cytotoxicity was closely related to the lipophilicity of compounds so that the
      most lipophilic compound (4g) revealed the highest activity and compound 4e as a
      more hydrophilic agent (Kpart; 0.05) showed the lowest cytotoxic effect. 

PMID- 24019829
TI  - Antioxidant and burn healing potential of Galium odoratum extracts.
AB  - This study was conducted to evaluate the burn wound healing and antioxidant
      activity of methanolic and aqueous extracts of Galium odoratum (L.) Scop. in
      rats. Second degree burn wounds were induced in six groups of six rats each.
      Groups 1 and 2 received eucerin and silver sulfadiazine as control and reference
      standard and groups 3, 4, 5 and 6 were given methanolic and aqueous extracts of
      15% and 30% (w/w in eucerin base) respectively. The topical treatment was done
      daily for 14 days. The percentage of wound contraction and histology parameters
      of healed wounds were observed. The antioxidant potential of both extracts was
      assessed by 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) assay. There was statistically
      significant improvement in wound contraction of animals treated with extracts in
      comparison to control (p < 0.001). The healed wounds in extracts-treated animals
      contained less inflammatory cells and had better reepithelialization. Wound
      contraction and histology parameters were relatively better in aqueous extract
      (90.68 +/- 6.13% and 97.18 +/- 4.37% for aqueous extracts of 15% and 30% in
      comparison to 79.29 +/- 9.16% and 91.94 +/- 4.14% for methanolic extracts of 15%
      and 30% respectively). In DPPH assay, both methanolic and aqueous extracts
      displayed significant antioxidant activity with IC50 values of 148 MUg/ml and 83
      MUg/ml, respectively. In conclusion, both extracts had desirable antioxidant
      potential plus experimentally and histologically ascertained burn wound healing
      activity, relatively better for aqueous extract. 

PMID- 24019830
TI  - Triterpenes from Euphorbia spinidens with immunomodulatory activity.
AB  - Dried aceton-chloroform extract of aerial parts of Euphorbia spinidens Bornm. ex
      Prokh. endemic to Iran, yielded two new triterpenoids, lup-20(29)-ene-33, 28 diol
      commonly known as betulin and (3beta,23E)-Cycloarta-23-ene-3,25-diol. The
      structures of the isolated compounds were elucidated by 13C- and 1H-NMR as well
      as 2D-NMR, IR and by the aid of mass fragmentation pattern. In phagocyte
      chemiluminescence assay, different concentrations of compounds were incubated
      with the human whole blood in triplicate and the chemiluminescence activity of
      phagocytic cells were measured by using serum opsonized zymosan and luminol. For
      lymphocyte proliferation assay, peripheral human blood lymphocytes were incubated
      with different concentrations of the test compound in supplemented Roswell Park
      Memorial Institute (RPMI) 1640 medium along with 5.0 MUg/ml phytohemagglutinin
      (PHA) at 37 degrees C in CO2 environment for 72 h and proliferation level was
      determined by Beta-scintillation counter. In phagocyte chemiluminescence assay,
      betulin showed moderate inhibitory effect on the oxidative burst in the
      neutrophils, while addition of betulin triterpene was able to stimulate the
      proliferation of the phytohemagglutinin (PHA) treated human peripheral blood
      lymphocytes (hPBLs). 

PMID- 24019831
TI  - The effect of different media composition and temperatures on the production of
      recombinant human growth hormone by CHO cells.
AB  - Cell lines derived from mammalian are dominant systems for the production of
      recombinant therapeutic proteins because of their capacity for correct protein
      folding, assembly and post-translational modification. In the search of an
      efficient method for the production of a recombinant protein using animal cell
      culture, we investigated the effects of different treatment including fetal calf
      serum concentration, glycerol and culture temperature on a Chinese hamster ovary
      (CHO) cell line on the production of recombinant human growth hormone (rhGH) and
      recombinant Chinese hamster ovary (rCHO) viability. The GH production was
      assessed using ELISA and western blotting methods and cell viability was
      determined by flow cytometry. The production of recombinant protein increased by
      2-fold when stimulatory chemical such as glycerol was added in two stages, first
      cells were cultured without glycerol for a period of time in order to obtain
      enough cell density and then glycerol was added to achieve high specific
      productivity.. Moreover, glycerol addition increased cell viability. Low culture
      temperature (below 37 degrees C) led to enhanced cellular productivity of the
      rhGH by 3-fold but decreased cell viability. These findings indicate that quite
      simple factors such as culture temperature and addition of simple chemicals may
      lead to the improvement of industrial process for the production of recombinant
      proteins such as rhGH. 

PMID- 24019833
TI  - A novel approach in assessment of root canal curvature.
AB  - INTRODUCTION: The purpose of this in vitro study was to introduce a new method to
      describe root canal curvatures and to assess the degree of curvature of human
      permanent mandibular teeth with curved root canals. MATERIALS AND METHODS: One
      hundred and thirty five mesial root canals of mandibular first and second molar
      teeth were selected. Access cavities were prepared. After inserting a K-file size
      #10 into each canal, radiographs were taken. Canal curvature was determined by
      measuring the Schneider angle, canal access angle, as well as the canal radius,
      length, height and curvature starting distance on scanned radiographs using a
      computerized image processing system. Data was evaluated statistically using
      Pearson correlation. RESULTS: The mean canal access angle (CAA) and Schneider
      angle (S) were 8.04(?) (3.46) and 19(?) (6.99), respectively. The Pearson
      correlation analysis found significant positive correlation between S and CAA
      (r=0.826, P<0.0001). Negative correlations were found between radius and length
      (r= -0.4, P<0.0001), radius and Schneider angle (r= -0.4, P<0.0001), radius and
      CAA (r= -0.24, P=0.004) and CAA and curvature starting distance (r= 0.4,
      P<0.0001). There was no correlation between height and distance (r=0.013,
      P=0.789), as well as CAA and height (r=0.654, P=0.001). CONCLUSION: Under the
      limitations of this study, the results indicated that the shape of root canal
      curvature can be more accurately described using two angles, Schneider in
      combination with Canal access angle. The related parameters included radius,
      length, distance and height of curvature. [Iranian Endodontic Journal
      2009;4(4):131-4].

PMID- 24019832
TI  - Comparing alveolar bone regeneration using Bio-Oss and autogenous bone grafts in
      humans: a systematic review and meta-analysis.
AB  - INTRODUCTION: Bone regeneration grafts (BRG) are widely used in the treatment of
      osseous defects and oral surgery. The various techniques and associated success
      rates of bone augmentation require evaluation by systematic review and meta
      analysis of eligible studies. The aim of this systematic review was to compare
      alveolar bone regeneration in humans using Bio-Oss and autogenous bone graft.
      MATERIALS AND METHODS: The computerized bibliographical databases including
      Pubmed, Google, ScienceDirect and Cochrane were searched for randomized and
      cohort studies in which autogenous grafts were compared to Bio-Oss in the
      treatment of periodontal defects. The inclusion criteria were human studies in
      English that were published 1998-2009. Exclusion criteria included non randomized
      observation and cohort studies, papers which provided summary statistics without
      the variance estimates, and studies that did not use BRG intervention alone, were
      excluded. The screening of eligible studies, assessment of the methodological
      quality of the trials and data extraction were collected by two observers
      independently. For comparing autogenous grafts used alone against Bio-Oss used
      alone 5 situations were investigated. Thirteen studies were included in the
      review which compared autogenous against Bio-Oss, autogenous combined with guided
      tissue regeneration (GTR) against GTR, Bio-Oss combined with GTR versus GTR,
      autogenous alone versus Open Flap Debridement (OFD), Bio-Oss versus OFD. In meta
      analysis, changes in bone level (bone fill) was used as the measure. Data were
      analyzed using Bayesian meta-analysis by WinBUGS and Boa software. RESULTS: Only
      one comparison demonstrated that the difference in bone augmentation between Bio
      Oss and OFD was statistically significant. CONCLUSION: There is insufficient
      evidence to show that Bio-Oss is superior to autogenous grafts in bone
      augmentation techniques however autogenous bone involves donor site surgery and
      thus donor site morbidity, so we can conclude that Bio-Oss is better than
      autogenous for alveolar regeneration. [Iranian Endodontic Journal 2009;4(4):125
      30].

PMID- 24019834
TI  - Comparison of apical debris extrusion using a conventional and two rotary
      techniques.
AB  - INTRODUCTION: Preparation techniques and instruments produce and push debris out
      of canals. This can induce inflammation within the periapical area. Therefore,
      instrumentation that causes less extrusion of debris is more desirable. The
      purpose of this in vitro study was to evaluate the quantity of debris extruded
      from the apical foramen during root canal preparation by using one hand, and two
      rotary instrumentation techniques. MATERIALS AND METHODS: Three different groups
      each with 12 mesiobuccal roots of human maxillary first molar were instrumented
      using either step-back technique with hand instruments, FlexMaster or Mtwo rotary
      system. Debris extruded from the apical foramen during canal preparation was
      collected. The mean dry weights of debris were compared using one-way ANOVA.
      RESULTS: Step-back group had a significantly greater mean weight of debris
      compared to the other two groups (P<0.05). Mtwo group had the lowest mean weight
      of debris, though it was not significantly different from FlexMaster group.
      CONCLUSION: According to this study, the engine driven techniques were associated
      with less apical debris extrusion. [Iranian Endodontic Journal 2009;4(4):135-8].

PMID- 24019835
TI  - Influence of Bovine Serum Albumin on the Antibacterial Activity of Endodontic
      Irrigants against Enterococcus Faecalis.
AB  - INTRODUCTION: It has been demonstrated that organic content of the root canals
      can influence the antimicrobial capability of chemical irrigants. The aim of this
      study was to evaluate the effect of bovine serum albumin (BSA), as an organic
      material, on the antimicrobial activity of several intracanal irrigants.
      MATERIALS AND METHODS: Bactericidal activity of Ethylenediaminetetraacetic acid
      (EDTA) 17%, citric acid 10%, Sodium hypochlorite (NaOCl) 5.25%, Chlorhexidine
      0.2% (CHX), Smear Clear and Cetrimide 0.5% were tested by means of dilution
      neutralization method. Contact times were 10 and 30 seconds, 5, 10, 30, 60
      minutes and 24 hours. First 950 lambda of the medicament was mixed with 50 lambda
      of the bacterial suspension in an Eppendorf test tube. The suspensions were
      thoroughly mixed. Sterile water served as negative controls. After each contact
      time, 100 lambda of samples was transferred to the Eppendorf test tubes which
      contained neutralizers. After 5 minutes, 50 lambda of serial dilutions were
      cultured on brain heart infusion agar and incubated in aerobic conditions. Then
      colonies were counted and reported as cfu/mL. In half of the samples, medicaments
      were suspended in BSA 0.5% 30 minutes before examination to assess its possible
      inhibitory effect on the antibacterial activity. RESULTS: NaOCl 5.25%, Cetrimide
      0.5% and Smear Clear showed bactericidal activity within seconds after the
      incubation. BSA had no inhibitory effect on bactericidal activity of these three
      medicaments. CHX took 5 and10 minutes to kill all bacterial cells in the absence
      and presence of BSA, respectively. Citric acid and EDTA showed the least
      antibacterial activity. CONCLUSION: In this study, NaOCl 5.25%, Cetrimide 0.5%
      and Smear Clear were significantly more effective against E. faecalis than EDTA
      17% and citric acid 10% in the presence and absence of BSA. Also, in the presence
      of BSA, bactericidal activity of CHX 0.2% against E. faecalis was significantly
      more than EDTA after 10 and 30 minutes of contact time. EDTA and citric acid
      showed the least bactericidal activity. [Iranian Endodontic Journal 2009;4(4):139
      43].

PMID- 24019836
TI  - The effect of Er, Cr:YSGG laser irradiation on the apical leakage of retrograde
      cavity.
AB  - INTRODUCTION: Controversial results have been reported when organic acids,
      ultrasonic instruments and laser techniques were used to remove smear layer in
      endodontic treatments. The aim of this study was to evaluate the effect of
      removing debris and smear layer by Er,Cr:YSGG laser irradiation on the apical
      leakage of retrograde cavities. MATERIALS AND METHODS: In this ex vivo study, 24
      extracted mandibular single-rooted teeth were selected and instrumented up to K
      file size #35. Approximately 3 mm of root apices were dissected perpendicular to
      the root's long axis. Retrograde cavities with 3 mm depth were prepared and the
      teeth were randomly assigned to two groups. In one group, the retrograde cavities
      were filled with amalgam and in the other group, the dentinal surface of the
      retrograde cavities were lased with Er,Cr:YSGG laser (2W, 15 seconds, G4 tip).
      The cavities were filled with amalgam; all tooth surfaces except for dissected
      outsides were covered with blue wax. Then the teeth were immersed in 2% methylene
      blue dye for 48 hours. The amount of dye penetration into sagittal sections was
      measured by stereomicroscope at *20 magnification by two independent observers
      who were blinded to the experiment. Data were statistically analyzed using
      student t-test. RESULTS: This study demonstrated that dye penetration was 0.8 mm
      (+/-0.53) in the lased and 0.97 mm (+/-0.54) in the non-lased group. It showed
      that, Er,Cr:YSGG laser can remove the debris and smear layer and consequently
      reduces the amount of dye penetration, although, the difference between the two
      groups was not statistically significant. CONCLUSION: This study showed that dye
      penetration was less in lased group because of the better seal of the dissected
      surface due to the better removal of the debris and smear layer by laser; further
      investigations are recommended in this field. [Iranian Endodontic Journal
      2009;4(4):144-8].

PMID- 24019837
TI  - Comparison of apical microleakage using Ni-Ti with stainless steel finger
      spreaders.
AB  - INTRODUCTION: The purpose of this in vitro study was to compare apical
      microleakage after obturation with Nickel-Titanium (NiTi) compared to Stainless
      Steel (SS) finger spreaders. MATERIALS AND METHODS: Eighty straight single-rooted
      human teeth were instrumented using step-back technique. The specimens were
      randomly divided into four groups. The two experimental groups (n=30) and the
      negative control group (n=10) were obturated by lateral condensation technique
      with Ariadent gutta-percha and AH26 sealer. The roots in the positive control
      group (n=10) were instrumented but not obturated. In one group, SS and in another
      group NiTi spreaders were used. Microleakage evaluation was conducted using dye
      penetration method t-test was used for statistical analysis. RESULTS: The results
      showed statistically significant differences between NiTi and SS groups
      (P=0.022), with the greatest dye penetration in SS group and the least in NiTi
      group. CONCLUSION: According to the results of the present study using NiTi
      spreader decrease apical microleakage in endodontically treated teeth. [Iranian
      Endodontic Journal 2009;4(4):149-51].

PMID- 24019838
TI  - Comparing subcutaneous tissue responses to freshly mixed and set root canal
      sealers.
AB  - INTRODUCTION: The purpose of this study was to compare the subcutaneous tissue
      responses of freshly mixed or set endodontic root canal sealers (i.e. RoekoSeal,
      AH26, AH Plus) in Wistar Albino rats. MATERIALS AND METHODS: Seventy-two male
      albino rats weighing 200-250g were used. The animals were randomly divided into
      six groups of 12 rats each. Root canal sealers were implanted in subcutaneous
      tissue in both freshly mixed and set conditions. The animals were sacrificed
      after 7, 14, and, 60 days. After histological preparation and Hematoxylin and
      Eosin (H&E) staining, the specimens were evaluated for capsule thickness,
      severity and extent of inflammation, and necrosis. Results were statistically
      analyzed using Multivariate ANOVA test. RESULTS: Differences between set and
      freshly mixed root canal sealers were significant (P=0.014), but not significant
      between test materials and controls, except for capsule thickness and extent of
      inflammation between control and AH26 (P=0.019 and P=0.006 respectively). The
      interaction between the type of material and setting condition was significant
      for capsule thickness and severity of inflammation in AH26 specimens at 14 and 60
      days (P=0.001). CONCLUSION: Based on the results of this study assessing the
      biocompatibility, both set and freshly mixed states can be used. [Iranian
      Endodontic Journal 2009;4(4):152-7].

PMID- 24019839
TI  - Central Giant Cell Granuloma: A potential endodontic misdiagnosis.
AB  - Central Giant Cell Granulomas (CGCGs) may manifest as radiolucencies anywhere in
      the mandible or maxilla. In rare cases, it can appear as a localized
      periradicular area and mimic an endodontic lesion. This case report presents an
      uncommon location of CGCG which was not accurately diagnosed nor timely treated.
      Periodic follow ups of periapical radiolucencies after RCT are necessary.
      Dentists should include CGCG in differential diagnosis of lesions that are
      refractory to endodontic treatment. [Iranian Endodontic Journal 2009;4(4):158
      60]. 

PMID- 24019840
TI  - The current status of the Korean student health examination.
AB  - Recent trends place an emphasis on school health care, the ultimate goal of which
      is to protect, maintain, and promote students' health. School health care is a
      program that integrates health care services, health education, health
      counseling, and local social health services. The student health examination
      (SHE) system is a part of school health care and schools and communities must be
      available to provide professional health services. Pediatricians also have
      important roles as experts in both school health care and the SHE system. In this
      article, the history of school health care, its legal basis, and the current
      status of the SHE system in Korea are reviewed. Furthermore, sample surveys from
      the past few years are reviewed. Through this holistic approach, future
      directions are proposed for the improvement of SHE and school health care. 

PMID- 24019841
TI  - Clinical approach to quality of life in children with end-stage renal disease.
AB  - Quality of life in addition to various medical problems in children with end
      stage renal disease (ESRD) should be objectively assessed to accomplish normal
      growth and development during childhood. However, unfortunately, studies of
      quality of life (QoL) in children with ESRD have been not popular yet and there
      are only fewer suitable assessment tools compared with adults. Recently, disease
      specific modules to evaluate QoL in children with chronic disease such as ESRD
      have been developed. This review was made to introduce these QoL instruments for
      children and help the clinical application of them. 

PMID- 24019842
TI  - Lower fat and better quality diet therapy for children with pharmacoresistant
      epilepsy.
AB  - The ketogenic diet (KD) is an established, effective, nonpharmacologic treatment
      for children with pharmacoresistant epilepsy. Although the KD is the most well
      established dietary therapy for epilepsy, it is too restrictive and is associated
      with serious complications; therefore, alternative lower-fat diets, including a
      modified Atkins diet and low-glycemic index diet, have been developed. Recent
      ongoing clinical evidence suggests that other dietary therapies have an efficacy
      almost comparable to that of the KD. In addition, a diet rich in polyunsaturated
      fatty acids appears to increase the efficacy of diet therapy and reduce the
      complications of a high-fat diet. Here, we review the systematic information
      about lower-fat diets and better-quality dietary therapies and the current
      clinical status of each of these dietary approaches. 

PMID- 24019843
TI  - Early-onset sepsis in a neonatal intensive care unit in Beni Suef, Egypt:
      bacterial isolates and antibiotic resistance pattern.
AB  - PURPOSE: To identify the frequency of bacterial isolates in early-onset neonatal
      sepsis (EONS) and their antimicrobial resistance pattern. METHODS: A
      retrospective study of EONS was conducted at the Beni Suef University Hospital
      from September 2008 to September 2012. A case of EONS was defined as an infant
      who had clinical signs of infection or who was born to a mother with risk factors
      for infection, and in whom blood culture obtained within 72 hours of life grew a
      bacterial pathogen. RESULTS: Of 673 neonates screened, there were 138 positive
      blood cultures (20.5%) (confirmed EONS). Of the recovered isolates, 86.2% were
      gram-negative pathogens. Klebsiella pneumoniae (42.8%), Enterobacter cloacae
      (22.5%), and Escherichia coli (13.8%) were the commonest isolated organisms. The
      most common gram-positive microorganism was Staphylococcus aureus accounting for
      only 12 isolates (8.7%). All Klebsiella isolates and 93% of Enterobacter isolates
      were resistant to ampicillin. Gram-negative pathogens had the maximum overall
      sensitivity to imipenem, cefepime, and ciprofloxacin; whereas, gram-positive
      isolates were most susceptible to vancomycin, imipenem, and piperacillin.
      CONCLUSION: K. pneumoniae was the predominant causative bacteria of EONS followed
      by E. cloacae and E. coli. There was a high resistance to ampicillin. Imipenem
      had the maximum overall activity against the causative bacteria. Continuous
      surveillance is needed to monitor the changing epidemiology of pathogens and
      antibiotic sensitivity.

PMID- 24019844
TI  - Prevalence and comorbidity of allergic diseases in preschool children.
AB  - PURPOSE: Allergic disease and its comorbidities significantly influence the
      quality of life. Although the comorbidities of allergic diseases are well
      described in adult populations, little is known about them in preschool children.
      In the present study, we aimed to assess the prevalence and comorbidity of
      allergic diseases in Korean preschool children. METHODS: We conducted a cross
      sectional study comprising 615 Korean children (age, 3 to 6 years). Symptoms of
      allergic diseases were assessed using the Korean version of the International
      Study of Asthma and Allergies in Childhood (ISAAC) questionnaire that was
      modified for preschool children. Comorbidities of allergic diseases were assessed
      by 'In the last 12 months, has your child had symptoms?'. RESULTS: The prevalence
      of symptoms of asthma, allergic rhinitis, and atopic dermatitis as recorded using
      the ISAAC questionnaire, within the last 12 months was 13.8%, 40.7%, and 20.8%,
      respectively. The symptom rates of allergic conjunctivitis, food allergy, and
      drug allergy were 14.8%, 10.4%, and 0.8%, respectively. The prevalence of
      allergic rhinitis in children with asthma was 64.3% and that of asthma in
      children with allergic rhinitis was 21.6%. The prevalence of rhinitis in children
      with conjunctivitis was 64.8% and that of conjunctivitis in children with
      rhinitis was 23.6%. CONCLUSION: The prevalence of current rhinitis in our
      preschool children is shown to be higher than that previously reported. Allergic
      conjunctivitis is closely associated with asthma and allergic rhinitis. However,
      further studies are warranted to determine the prevalence and effects of these
      comorbidities on health outcomes in preschool children.

PMID- 24019845
TI  - Efficacy of imatinib mesylate-based front-line therapy in pediatric chronic
      myelogenous leukemia.
AB  - PURPOSE: Despite the established role of imatinib (IM) in chronic myelogenous
      leukemia (CML) in adults, there are few reports on its efficacy in children. In
      this study, we compared the outcomes of children with CML before and after the
      advent of IM-based treatment. METHODS: The study cohort consisted of 52 patients
      treated for CML at the Department of Pediatrics, The Catholic University of Korea
      from January 1995 to October 2010. Patients were divided and analyzed according
      to the preImatinib group (pre-IMG) and imatinib group (IMG). RESULTS: Median age
      at diagnosis for the overall cohort (pre-IMG, n=27; IMG, n=25) was 9 years, with
      a median follow-up duration of survivors of 84 months. Except for 5 patients in
      the IMG, all were diagnosed in chronic phase (CP). The overall survival (OS) of
      patients diagnosed in CP was 45.7% and 89.7% for pre-IMG and IMG, respectively
      (P=0.025). The OS of hematopoietic stem cell transplantation (HSCT) recipients in
      the 2 groups was similar, but the OS of patients diagnosed in CP who did not
      receive HSCT was superior in IMG (91.7% vs. 16.7%, P=0.014). Of the 12 patients
      in IMG who remained on IM without HSCT, 2 showed disease progression, compared to
      11 of 12 in pre-IMG. No difference was observed in the progression free survival
      (PFS) of matched donor HSCT recipients and IM-based treatment recipients.
      CONCLUSION: Similar PFS of patients treated with IM and those who received
      matched donor HSCT underscore the potential of IM as effective first-line
      treatment in childhood CML.

PMID- 24019846
TI  - Chronic intermittent form of isovaleric aciduria in a 2-year-old boy.
AB  - Isovaleric aciduria (IVA) is caused by an autosomal recessive deficiency of
      isovaleryl-CoA dehydrogenase (IVD). IVA presents either in the neonatal period as
      an acute episode of fulminant metabolic acidosis, which may lead to coma or
      death, or later as a "chronic intermittent form" that is associated with
      developmental delays, with or without recurrent acidotic episodes during periods
      of stress, such as infections. Here, we report the case of a 2-year old boy with
      IVA who presented with the chronic intermittent form. He was admitted to Asan
      Medical Center Children's Hospital with recurrent vomiting. Metabolic acidosis,
      hyperammonemia, elevated serum lactate and isovalerylcarnitine levels, and
      markedly increased urine isovalerylglycine concentration were noted. Sequence
      analysis of the IVD gene in the patient revealed the novel compound mutations-a
      missense mutation, c.986T>C (p.Met329Thr) and a frameshift mutation, c.1083del
      (p.Ile361fs*11). Following stabilization during the acute phase, the patient has
      remained in a stable condition on a low-leucine diet. 

PMID- 24019847
TI  - A novel MLL2 gene mutation in a Korean patient with Kabuki syndrome.
AB  - Kabuki syndrome (KS) is a rare genetic disease with a distinctive dysmorphic
      face, intellectual disability, and multiple congenital abnormalities. KS is
      inherited in an autosomal dominant manner. As the primary cause of KS, MLL2
      mutations have been identified in 56-76% of affected individuals who have been
      tested, suggesting that there may be additional genes associated with KS.
      Recently, a few KS individuals have been found to have de novo partial or
      complete deletions of an X chromosome gene, KDM6A, which encodes a histone
      demethylase that interacts with MLL2. Nevertheless, mutations in MLL2 are the
      major cause of KS. Although there are a few reports of KS patients in Korea, none
      of these had been confirmed by genetic analysis. Here, we report a case of a
      Korean patient with clinical features of KS. Using direct sequencing, we
      identified a frameshift heterozygous mutation for MLL2:
      (c.5256_5257delGA;p.Lys1753Alafs*34). Clinically, the patient presented with
      typical facial features, and diagnosis of KS was based on the diagnostic
      criteria. While KS is a rare disease, other malformations that overlap with those
      found in individuals with KS are common. Hence, the diagnosis of KS by mutational
      analysis can be a valuable method for patients with KS-like syndromes.
      Furthermore, in the near future, other genes could be identified in patients with
      KS without a detectable MLL2 mutation. 

PMID- 24019848
TI  - Highlights from the 2013 Science of Placebo thematic workshop.
AB  - In the last 30 years, a converging series of laboratory experiments, clinical
      trials, and neurocognitive studies have identified several key mechanisms of
      placebo effects. These studies suggest not only that placebo responses may be
      ubiquitous across research and clinical settings, but also that they can
      significantly modulate symptoms across a wide spectrum of highly prevalent
      conditions such as acute pain, chronic pain, anxiety, depression, Parkinson's
      disease, and nausea, just to name a few. In order to inform the medical community
      about the most recent advances in the field of placebo studies, a thematic
      workshop entitled "The Science of Placebo" was held at the Beth Israel
      Deaconesses Medical Center (BIDMC), Harvard Medical School, in Boston (MA), on
      the 19-20 of June 2013. The workshop, sponsored by The Robert Wood Johnson
      Foundation, was organised by the Program in Placebo Studies and the Therapeutic
      Encounter, a Harvard-wide network of researchers dedicated to the study of the
      placebo phenomenon hosted by the BIDMC. The event was structured as a series of
      four public lectures, each delivered by a leading investigator in the field of
      placebo studies. The four keynote speakers were Fabrizio Benedetti, professor of
      neurophysiology and human physiology at the University of Turin Medical School
      and at the National Institute of Neuroscience in Italy; Tor Wager, director of
      the Cognitive and Affective Control Laboratory and associate professor of
      psychology and neuroscience at the University of Colorado; Predrag Petrovic,
      psychiatrist and researcher in the Department of Clinical Neuroscience at the
      Karolinska Institute in Stockholm; and Ted Kaptchuk, director of the Program in
      Placebo Studies and associate professor of medicine at Harvard Medical School. 

PMID- 24019849
TI  - A caveat concerning center of resistance.
AB  - The center of resistance is a concept in theoretical orthodontics used to
      describe tooth movement under loads. It is commonly used to qualitatively predict
      tooth movement without recourse to complex equations or simulations. We start
      with a survey of the historical origin of the technical term. After this, the
      periodontal ligament is idealized as a linear elastic suspension. The
      mathematical formalism of vector and tensor calculus will clarify our reasoning.
      We show that a point such as the center of resistance basically only exists in
      two dimensions or in very special symmetric spatial configurations. In three
      dimensions, a simple counterexample of a suspension without a center of
      resistance is given. A second more tooth-like example illustrates the magnitude
      of the effects in question in dentistry. In conclusion, the center of resistance
      should be replaced by a newer and wider mathematical concept, the "center of
      elasticity," together with a limiting parameter, the "radius of resistance." 

PMID- 24019850
TI  - Device and materials for in vitro evaluation of forces developed to teeth and
      periodontal structures during dental practices.
AB  - This study aimed at providing a gauge device (Ekontak et al Gauge K-Device) in
      order to analyze the forces applied to teeth and periodontal tissues during
      dental practices in vitro. This force gauge device can be used in the
      investigation of the possible defect generation to tooth structures when
      overloaded forces are applied during dental procedures in vitro. Ekontak et al
      Gauge K-Device consists of three units: the specimen's holder, a high-performance
      digital force gauge, and the support frame. The holder was fabricated by an Al
      alloy providing a steady detachable attachment between the specimens and the
      force gauge's pin connector. The clinical simulation was achieved with the use of
      a proper silicone material, selected to provide similar elastic behavior with the
      human periodontal ligament and to join the teeth inside a solid matrix of an
      acrylic resin. The digital force gauge is a high-speed collection and recording
      (1000 Hz) product coupled with data recording software. The forces developed to
      15 specimens' root canals during lateral condensation and vertical compaction of
      cold gutta-percha obturation procedures were monitored, saved as graphs, CSV, and
      excel files and presented over time. The forces developed during vertical
      compaction (mean maximum force per obturation circle = 13.22 N) were more
      excessive than those during lateral condensation (mean maximum force per
      obturation circle = 10.14 N). In conclusion, Ekontak et al Gauge K-Device is
      provided as a modern gauge device, capable of performing clinical simulation in
      vitro, under the terms of its protocol. 

PMID- 24019851
TI  - Multifunctional gold nanostar conjugates for tumor imaging and combined
      photothermal and chemo-therapy.
AB  - Uniform gold nanostars (Au NS) were conjugated with cyclic RGD (cRGD) and near
      infrared (NIR) fluorescence probe (MPA) or anti-cancer drug (DOX) to obtain multi
      functional nanoconstructs, Au-cRGD-MPA and Au-cRGD-DOX respectively. The NIR
      contrast agent Au-cRGD-MPA was shown to have low cytotoxicity. Using tumor cells
      and tumor bearing mice, these imaging nanoparticles demonstrated favorable tumor
      targeting capability mediated by RGD peptide binding to its over-expressed
      receptor on the tumor cells. The multi-therapeutic analogue, Au-cRGD-DOX,
      integrates targeting tumor, chemotherapy and photo-thermotherapy into a single
      system. The synergistic effect of photo-thermal therapy and chemotherapy was
      demonstrated in different tumor cell lines and in vivo using S180 tumor-bearing
      mouse models. The viability of MDA-MB-231 cells was only 40 % after incubation
      with Au-cRGD-DOX and irradiation with NIR light. Both tail vein and intratumoral
      injections showed Au-cRGD-DOX treated mice exhibiting the slowest tumor increase.
      These results indicate that the multifunctional nanoconstruct is a promising
      combined therapeutic agent for tumor-targeting treatment, with the potential to
      enhance the anti-cancer treatment outcomes.

PMID- 24019852
TI  - Surface passivation of carbon nanoparticles with branched macromolecules
      influences near infrared bioimaging.
AB  - A superior and commercially exploitable 'green synthesis' of optically active
      carbon nanoparticle (OCN) is revealed in this work. The naked carbon particles
      (<20 nm) were derived from commercial food grade honey. The fluorescence
      properties of these particles were significantly enhanced by utilizing
      hyberbranched polymer for surface passivation. A dramatic increase in near
      infrared emission was achieved compared to a linear polymer (PEG) coated carbon
      nanoparticles. Interestingly, as passivating agent becomes more extensively
      branched (pseudo generation 2 to 4), the average radiant efficiency amplifies
      considerably as a direct result of the increasing surface area available for
      light passivation. The particles showed negligible loss of cell viability in
      presence of endothelial cells in vitro. Preliminary in vivo experiment showed
      high contrast enhancement in auxiliary lymphnode in a mouse model. The
      exceptionally rapid lymphatic transport of these particles suggests that such an
      approach may offer greater convenience and reduced procedural expense, as well as
      improved surgical advantage as the patient is positioned on the table for easier
      resection.

PMID- 24019853
TI  - Tumor Spheroids as an in vitro model for determining the therapeutic response to
      proton beam radiotherapy and thermally sensitive nanocarriers.
AB  - Multicellular Tumor Spheroids (MCTS) strongly resemble tumor tissues, which makes
      them useful tools for radiation biology studies and screening of various
      chemotherapeutics. The goal of this pilot study was to use MCTS as an in vitro
      model to determine the response of cells to low temperature-sensitive liposomes
      (LTSLs) encapsulating doxorubicin (Dox) and proton beam radiotherapy (PBRT).
      Prior to treatment, MCTS were characterized for morphology and LTSLs were
      characterized for size, encapsulation efficiency, and ability to thermally
      release Dox (a model anticancer agent). Two groups of MCTS were treated with LTSL
      in combination with mild hyperthermia (40-42  degrees C) or PBRT alone in the
      presence of appropriate controls. Cytotoxic response was assessed after 48-72 h
      using an acid phosphatase assay. At 72 h, LTSL in combination with heat
      significantly reduced the viability of MCTS (15-30%) compared to the control (P <
      0.05). A similar cytotoxic response was observed with PBRT treatment. The data
      suggest that like a monolayer cell culture, MCTS can be used to determine
      cytotoxic outcomes of thermal and proton therapy.

PMID- 24019854
TI  - Evaluation of polymethine dyes as potential probes for near infrared fluorescence
      imaging of tumors: part - 1.
AB  - Near-infrared (NIR) organic dyes have become important for many biomedical
      applications, including in vivo optical imaging. Conjugation of NIR fluorescent
      dyes to photosensitizing molecules (photosensitizers) holds strong potential for
      NIR fluorescence image guided photodynamic therapy (PDT) of cancer. Therefore, we
      were interested in investigating the photophysical properties, in vivo tumor
      affinity and fluorescence imaging potential of a series of heterocyclic
      polymethine dyes, which could then be conjugated to certain PDT agents. For our
      present study, we selected a series of symmetrical polymethine dyes containing a
      variety of bis-N-substituted indole or benzindole moieties linked by linear
      conjugation with and without a fused substituted cyclohexene ring. The N-alkyl
      side chain at the C-terminal position was functionalized with sulfonic,
      carboxylic acid, methyl ester or hydroxyl groups. Although, among the parent
      cyanine dyes investigated, the commercially available, cyanine dye IR783 (3) (bis
      indole-N-butylsulfonate)-polymethine dye with a cyclic chloro-cyclohexene moiety
      showed best fluorescence-imaging ability, based on its spectral properties
      (lambdaAbs=782 nm, lambdaFl=810 nm, epsilon = 261,000 M(-1)cm(-1), PhiFl~0.08)
      and tumor affinity. In addition to 3, parent dyes IR820 and Cypate (6) were also
      selected and subjected to further modifications by introducing desired functional
      groups, which could enable further conjugation of the cyanine dyes to an
      effective photosensitizer HPPH developed in our laboratory. The synthesis and
      biological studies (tumor-imaging and PDT) of the resulting bifunctional
      conjugates are discussed in succeeding paper (Part-2 of this study).

PMID- 24019855
TI  - Comparative tumor imaging and PDT Efficacy of HPPH conjugated in the mono- and di
      forms to various polymethine cyanine dyes: part - 2.
AB  - Previous reports from our laboratory have shown that a bifunctional agent
      obtained by conjugating a photosensitizer (HPPH) to a cyanine dye (CD) can be
      used for fluorescence image-guided treatment of tumor by photodynamic therapy
      (PDT). However, the resulting HPPH-CD conjugate showed a significant difference
      between the tumor-imaging and therapeutic doses. It was demonstrated that the
      singlet oxygen ( (1) O 2 (*), a key cytotoxic agent in PDT) produced by the
      conjugate upon excitation of the HPPH moiety was partially quenched by the CD
      moiety; this resulted in a reduced PDT response when compared to HPPH-PDT under
      similar treatment parameters. To improve the therapeutic potential of the
      conjugate, we synthesized a series of dual functional agents in which one or two
      HPPH moieties were separately conjugated to three different dyes (Cypate,
      modified IR820 or modified IR783). The newly synthesized conjugates were compared
      with our lead compound HPPH-CD in terms of photophysical properties, in vitro and
      in vivo PDT efficacy, tumor uptake and imaging potential. Among the analogs
      investigated, the conjugate, in which two HPPH moieties were linked to the
      modified IR820 produced enhanced tumor uptake and tumor contrast in both Colon 26
      (a murine Colon carcinoma) and U87 (a human glioblastoma) cell lines. The long
      term PDT efficacy (cure) of this conjugate in BALB/c mice, bearing Colon 26
      tumors was also enhanced; however, its efficacy in Nude mice bearing U87 tumors
      was slightly reduced. It was also found that in all the conjugates the singlet
      oxygen generation and, consequently, PDT efficacy were compromised by a competing
      pathway, whereby an electronic excitation of HPPH, the energy donor, is
      deactivated through an electronic excitation energy transfer (Forster Resonance
      Energy Transfer, FRET) to the CD fluorophore, the energy acceptor, resulting in
      overall reduction of the singlet oxygen production. Conjugates with increased
      FRET showed reduced singlet oxygen production and PDT efficacy. Among the
      conjugates investigated, the bifunctional agent in which two HPPH moieties were
      linked to the benzoindole-based cyanine dye 11 showed superiority over the lead
      candidate 9 (mono HPPH-cyanine dye).

PMID- 24019857
TI  - Photoselective vaporization for the treatment of benign prostatic hyperplasia.
AB  - BACKGROUND: As an alternative to transurethral resection of the prostate (TURP),
      photoselective vaporization of the prostate (PVP) provides a bloodless,
      relatively painless relief of lower urinary tract symptoms for men with benign
      prostatic hyperplasia. Following a review of the evidence in 2006, the Ontario
      Health Technology Advisory Committee recommended that a study be conducted to
      evaluate PVP in Ontario. OBJECTIVES: To compare the clinical effectiveness,
      safety, cost-effectiveness, and budget impact of PVP compared to conventional
      TURP for the treatment of benign prostatic hyperplasia in Ontario. METHODS: A
      prospective, nonrandomized trial was conducted in 3 Ontario centres. Consenting
      subjects were assessed at baseline and 1, 3, and 6 months following surgery.
      Outcome measures included International Prostate Symptom Score (IPSS), peak
      urinary flow rate (Qmax), post-void residual (PVR) volume, prostate-specific
      antigen (PSA), health-related quality of life (HRQOL) using the EuroQol 5 Domain
      questionnaire, and the Sexual Health Inventory for Men (SHIM) score. Adverse
      events, resource utilization, and productivity losses were also assessed. Cost
      effectiveness and budget impact analyses were completed using data from the
      study. RESULTS: Between February 2008 and August 2010, 164 subjects were enrolled
      in the study (n = 140 for PVP and n = 24 for TURP). Treatment outcomes were
      similar between the 2 groups at 6 months, with the IPSS decreasing similarly over
      time (P = 0.718). For other treatment outcomes (Qmax, PSA, HRQOL, SHIM) both
      treatments provided similar benefit over time; only changes in PVR volume
      favoured PVP (P = 0.018). The majority of PVP patients were managed on an
      outpatient basis, with only 7.1% requiring admission (all TURP subjects were
      inpatients). At 6 months, PVP was less costly than TURP ($3,891 versus $4,863; P
      = 0.001), with similar quality-adjusted life-years (0.448 versus 0.441; P =
      0.658). PVP remained the most cost-effective treatment across all decision-making
      thresholds, with the technology costing less and providing similar clinical
      outcomes. Extrapolating the results to a provincial level indicated (based on an
      estimated case volume of 12,335 TURPs) that there is an opportunity to reallocate
      just over $14 million (Cdn), primarily related to the reduced need for hospital
      admission. LIMITATIONS: This study was nonrandomized, and the results should be
      interpreted with some caution, despite generally similar baseline characteristics
      between the 2 groups. Recruiting individuals to the TURP arm was a challenge,
      resulting in a size imbalance between treatment arms. CONCLUSIONS: Based on this
      analysis, PVP appears to be a cost-effective alternative to TURP, providing
      similar clinical benefit at a lower cost to the health system.

PMID- 24019858
TI  - Rapid detection of live methicillin-resistant Staphylococcus aureus by using an
      integrated microfluidic system capable of ethidium monoazide pre-treatment and
      molecular diagnosis.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium resistant to
      all existing penicillin and lactam-based antimicrobial drugs and, therefore, has
      become one of the most prevalent antibiotic-resistant pathogens found in
      hospitals. The multi-drug resistant characteristics of MRSA make it challenging
      to clinically treat infected patients. Therefore, early diagnosis of MRSA has
      become a public-health priority worldwide. Conventionally, cell-culture based
      methodology and microscopic identification are commonly used for MRSA detection.
      However, they are relatively time-consuming and labor-intensive. Recently,
      molecular diagnosis based on nucleic acid amplification techniques, such as
      polymerase chain reaction (PCR), has been widely investigated for the rapid
      detection of MRSA. However, genomic DNA of both live and dead pathogens can be
      distinguished by conventional PCR. These results thus could not provide
      sufficient confirmation of an active infection for clinicians. In this study,
      live MRSA was rapidly detected by using a new integrated microfluidic system. The
      microfluidic system has been demonstrated to have 100% specificity to detect live
      MRSA with S. aureus and other pathogens commonly found in hospitals. The
      experimental results showed that the limit of detection for live MRSA from
      biosamples was approximately 10(2) CFU/MUl. In addition, the entire diagnostic
      protocol, from sample pre-treatment to fluorescence observation, can be
      automatically completed within 2.5 h. Consequently, this microfluidic system may
      be a powerful tool for the rapid molecular diagnosis of live MRSA. 

PMID- 24019856
TI  - Bioengineering silicon quantum dot theranostics using a network analysis of
      metabolomic and proteomic data in cardiac ischemia.
AB  - Metabolomic profiling is ideally suited for the analysis of cardiac metabolism in
      healthy and diseased states. Here, we show that systematic discovery of
      biomarkers of ischemic preconditioning using metabolomics can be translated to
      potential nanotheranostics. Thirty-three patients underwent percutaneous coronary
      intervention (PCI) after myocardial infarction. Blood was sampled from catheters
      in the coronary sinus, aorta and femoral vein before coronary occlusion and 20
      minutes after one minute of coronary occlusion. Plasma was analysed using GC-MS
      metabolomics and iTRAQ LC-MS/MS proteomics. Proteins and metabolites were mapped
      into the Metacore network database (GeneGo, MI, USA) to establish functional
      relevance. Expression of 13 proteins was significantly different (p<0.05) as a
      result of PCI. Included amongst these was CD44, a cell surface marker of
      reperfusion injury. Thirty-eight metabolites were identified using a targeted
      approach. Using PCA, 42% of their variance was accounted for by 21 metabolites.
      Multiple metabolic pathways and potential biomarkers of cardiac ischemia,
      reperfusion and preconditioning were identified. CD44, a marker of reperfusion
      injury, and myristic acid, a potential preconditioning agent, were incorporated
      into a nanotheranostic that may be useful for cardiovascular applications.
      Integrating biomarker discovery techniques into rationally designed
      nanoconstructs may lead to improvements in disease-specific diagnosis and
      treatment.

PMID- 24019859
TI  - Cost-effectiveness analysis of Tdap in the prevention of pertussis in the
      elderly.
AB  - OBJECTIVES: Health benefits and costs of combined reduced-antigen-content
      tetanus, diphtheria, and pertussis (Tdap) immunization among adults >=65 years
      have not been evaluated. In February 2012, the Advisory Committee on Immunization
      Practices (ACIP) recommended expanding Tdap vaccination (one single dose) to
      include adults >=65 years not previously vaccinated with Tdap. Our study
      estimated the health and economic outcomes of one-time replacement of the
      decennial tetanus and diphtheria (Td) booster with Tdap in the 10% of individuals
      aged 65 years assumed eligible each year compared with a baseline scenario of
      continued Td vaccination. METHODS: We constructed a model evaluating the cost
      effectiveness of vaccinating a cohort of adults aged 65 with Tdap, by calculating
      pertussis cases averted due to direct vaccine effects only. Results are presented
      from societal and payer perspectives for a range of pertussis incidences (25-200
      cases per 100,000), due to the uncertainty in estimating true annual incidence.
      Cases averted were accrued throughout the patient 's lifetime, and a probability
      tree used to estimate the clinical outcomes and costs (US$ 2010) for each case.
      Quality-adjusted life-years (QALYs) lost to acute disease were calculated by
      multiplying cases of mild/moderate/severe pertussis by the associated health
      state disutility; QALY losses due to death and long-term sequelae were also
      considered. Incremental costs and QALYs were summed over the cohort to derive
      incremental cost-effectiveness ratios. Scenario analyses evaluated the effect of
      alternative plausible parameter estimates on results. RESULTS: At incidence
      levels of 25, 100, 200 cases/100,000, vaccinating adults aged 65 years costs an
      additional $336,000, $63,000 and $17,000/QALY gained, respectively. Vaccination
      has a cost-effectiveness ratio less than $50,000/QALY if pertussis incidence is
      >116 cases/100,000 from societal and payer perspectives. Results were robust to
      scenario analyses. CONCLUSIONS: Tdap immunization of adults aged 65 years
      according to current ACIP recommendations is a cost-effective health-care
      intervention at plausible incidence assumptions.

PMID- 24019861
TI  - Expression of COX-2, CD44v6 and CD147 and relationship with invasion and lymph
      node metastasis in hypopharyngeal squamous cell carcinoma.
AB  - To assess the expression of COX-2,CD44v6 and CD147 in hypopharyngeal squamous
      cell carcinomas and the three biomarkers correlation with tumor invasion and
      lymph node metastasis of Chinese people. 101 cases of surgically excised primary
      tumor were included in this study, and 40 tissues of epithelium adjacent to
      carcinoma were used as controls. We characterized the immunohistochemical
      expression of COX-2, CD44v6, and CD147 in 141 formalin-fixed, paraffin-embedded
      tissues, and measured the mean optical density (OD) of the positive area to
      identify the expression of the three bio-markers and relationship with tumor
      invasion and lymph node metastasis. Our study demonstrates that the expression of
      the COX-2 and CD147 were significantly increased in carcinoma tissues compared to
      the epithelium adjacent to carcinoma. We also observed that the expression of COX
      2, CD44v6, and CD147 were significantly associated with T classification, lymph
      node metastasis and clinical stage. There was strong significant correlation
      among the three biomarkers as well. Additionally, we indicated that recurrence
      and >= P50 level of COX-2 expression had an independent prognostic effect on
      prognosis. In conclusion, the three biomarkers play important roles in tumor
      invasion and lymph node metastases and might be valuable indicators of tumor
      metastasis in hypopharyngeal squamous cell carcinoma.

PMID- 24019860
TI  - Metabolic and structural changes in lower-limb skeletal muscle following
      neuromuscular electrical stimulation: a systematic review.
AB  - BACKGROUND: Transcutaneous neuromuscular electrical stimulation (NMES) can be
      applied as a complementary intervention to regular exercise training programs. A
      distinction can be made between high-frequency (HF) NMES and low-frequency (LF)
      NMES. In order to increase understanding of the mechanisms of functional
      improvements following NMES, the purpose of this study was to systematically
      review changes in enzyme activity, muscle fiber type composition and muscle fiber
      size in human lower-limb skeletal muscles following only NMES. METHODS: Trials
      were collected up to march 2012 and were identified by searching the
      Medline/PubMed, EMBASE, Cochrane Central Register of Controlled Trials, CINAHL
      and The Physical Therapy Evidence Database (PEDro) databases and reference lists.
      18 trials were reviewed in detail: 8 trials studied changes in enzyme activities,
      7 trials studied changes in muscle fiber type composition and 14 trials studied
      changes in muscle fiber size following NMES. RESULTS: The methodological quality
      generally was poor, and the heterogeneity in study design, study population, NMES
      features and outcome parameters prohibited the use of meta-analysis. Most of the
      LF-NMES studies reported significant increases in oxidative enzyme activity,
      while the results concerning changes in muscle fiber composition and muscle size
      were conflicting. HF-NMES significantly increased muscle size in 50% of the
      studies. CONCLUSION: NMES seems to be a training modality resulting in changes in
      oxidative enzyme activity, skeletal muscle fiber type and skeletal muscle fiber
      size. However, considering the small sample sizes, the variance in study
      populations, the non-randomized controlled study designs, the variance in primary
      outcomes, and the large heterogeneity in NMES protocols, it is difficult to draw
      definitive conclusions about the effects of stimulation frequencies on muscular
      changes.

PMID- 24019862
TI  - Optical detection and virotherapy of live metastatic tumor cells in body fluids
      with vaccinia strains.
AB  - Metastatic tumor cells in body fluids are important targets for treatment, and
      critical surrogate markers for evaluating cancer prognosis and therapeutic
      response. Here we report, for the first time, that live metastatic tumor cells in
      blood samples from mice bearing human tumor xenografts and in blood and
      cerebrospinal fluid samples from patients with cancer were successfully detected
      using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the
      FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a
      cancer biomarker-independent manner, thus, free of any bias related to the use of
      antibodies, and can be potentially a universal system for detection of live CTCs
      of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we
      demonstrate for the first time that VACV was effective in preventing and reducing
      circulating tumor cells in mice bearing human tumor xenografts. Importantly, a
      single intra-peritoneal delivery of VACV resulted in a dramatic decline in the
      number of tumor cells in the ascitic fluid from a patient with gastric cancer.
      Taken together, these results suggest VACV to be a useful tool for quantitative
      detection of live tumor cells in liquid biopsies as well as a potentially
      effective treatment for reducing or eliminating live tumor cells in body fluids
      of patients with metastatic disease. 

PMID- 24019863
TI  - Ovarian volume throughout life: a validated normative model.
AB  - The measurement of ovarian volume has been shown to be a useful indirect
      indicator of the ovarian reserve in women of reproductive age, in the diagnosis
      and management of a number of disorders of puberty and adult reproductive
      function, and is under investigation as a screening tool for ovarian cancer. To
      date there is no normative model of ovarian volume throughout life. By searching
      the published literature for ovarian volume in healthy females, and using our own
      data from multiple sources (combined n=59,994) we have generated and robustly
      validated the first model of ovarian volume from conception to 82 years of age.
      This model shows that 69% of the variation in ovarian volume is due to age alone.
      We have shown that in the average case ovarian volume rises from 0.7 mL (95% CI
      0.4-1.1 mL) at 2 years of age to a peak of 7.7 mL (95% CI 6.5-9.2 mL) at 20 years
      of age with a subsequent decline to about 2.8 mL (95% CI 2.7-2.9 mL) at the
      menopause and smaller volumes thereafter. Our model allows us to generate normal
      values and ranges for ovarian volume throughout life. This is the first validated
      normative model of ovarian volume from conception to old age; it will be of use
      in the diagnosis and management of a number of diverse gynaecological and
      reproductive conditions in females from birth to menopause and beyond.

PMID- 24019864
TI  - Low openness on the revised NEO personality inventory as a risk factor for
      treatment-resistant depression.
AB  - BACKGROUND: Recently, we reported that low reward dependence, and to a lesser
      extent, low cooperativeness in the Temperature and Character Inventory (TCI) may
      be risk factors for treatment-resistant depression. Here, we analyzed additional
      psychological traits in these patients. METHODS: We administered Costa and
      McCrae's five-factor model personality inventory, NEO Personality Inventory
      Revised (NEO-PI-R), to antidepressant-treatment resistant depressed patients
      (n=35), remitted depressed patients (n=27), and healthy controls (n=66). We also
      evaluated the relationships between scores on NEO and TCI, using the same cohort
      of patients with treatment-resistant depression, as our previous study. RESULTS:
      Patients with treatment-resistant depression showed high scores for neuroticism,
      low scores for extraversion, openness and conscientiousness, without changes in
      agreeableness, on the NEO. However, patients in remitted depression showed no
      significant scores on NEO. Patients with treatment-resistant depression and low
      openness on NEO showed positive relationships with reward dependence and
      cooperativeness on the TCI. CONCLUSIONS: Many studies have reported that
      depressed patients show high neuroticism, low extraversion and low
      conscientiousness on the NEO. Our study highlights low openness on the NEO, as a
      risk mediator in treatment-resistant depression. This newly identified trait
      should be included as a risk factor in treatment-resistant depression.

PMID- 24019865
TI  - Bacteria- and IMD pathway-independent immune defenses against Plasmodium
      falciparum in Anopheles gambiae.
AB  - The mosquito Anopheles gambiae uses its innate immune system to control bacterial
      and Plasmodium infection of its midgut tissue. The activation of potent IMD
      pathway-mediated anti-Plasmodium falciparum defenses is dependent on the presence
      of the midgut microbiota, which activate this defense system upon parasite
      infection through a peptidoglycan recognition protein, PGRPLC. We employed
      transcriptomic and reverse genetic analyses to compare the P. falciparum
      infection-responsive transcriptomes of septic and aseptic mosquitoes and to
      determine whether bacteria-independent anti-Plasmodium defenses exist. Antibiotic
      treated aseptic mosquitoes mounted molecular immune responses representing a
      variety of immune functions upon P. falciparum infection. Among other immune
      factors, our analysis uncovered a serine protease inhibitor (SRPN7) and Clip
      domain serine protease (CLIPC2) that were transcriptionally induced in the midgut
      upon P. falciparum infection, independent of bacteria. We also showed that SRPN7
      negatively and CLIPC2 positively regulate the anti-Plasmodium defense,
      independently of the midgut-associated bacteria. Co-silencing assays suggested
      that these two genes may function together in a signaling cascade. Neither gene
      was regulated, nor modulated, by infection with the rodent malaria parasite
      Plasmodium berghei, suggesting that SRPN7 and CLIPC2 are components of a defense
      system with preferential activity towards P. falciparum. Further analysis using
      RNA interference determined that these genes do not regulate the anti-Plasmodium
      defense mediated by the IMD pathway, and both factors act as agonists of the
      endogenous midgut microbiota, further demonstrating the lack of functional
      relatedness between these genes and the bacteria-dependent activation of the IMD
      pathway. This is the first study confirming the existence of a bacteria
      independent, anti-P. falciparum defense. Further exploration of this anti
      Plasmodium defense will help clarify determinants of immune specificity in the
      mosquito, and expose potential gene and/or protein targets for malaria
      intervention strategies based on targeting the parasite in the mosquito vector. 

PMID- 24019867
TI  - Entangled parametric hierarchies: problems for an overspecified universal
      grammar.
AB  - This study addresses the feasibility of the classical notion of parameter in
      linguistic theory from the perspective of parametric hierarchies. A novel program
      based analysis is implemented in order to show certain empirical problems related
      to these hierarchies. The program was developed on the basis of an enriched data
      base spanning 23 contemporary and 5 ancient languages. The empirical issues
      uncovered cast doubt on classical parametric models of language acquisition as
      well as on the conceptualization of an overspecified Universal Grammar that has
      parameters among its primitives. Pinpointing these issues leads to the proposal
      that (i) the (bio)logical problem of language acquisition does not amount to a
      process of triggering innately pre-wired values of parameters and (ii) it paves
      the way for viewing language, epigenetic ('parametric') variation as an
      externalization-related epiphenomenon, whose learning component may be more
      important than what sometimes is assumed. 

PMID- 24019866
TI  - Geographically structured populations of Cryptococcus neoformans Variety grubii
      in Asia correlate with HIV status and show a clonal population structure.
AB  - Cryptococcosis is an important fungal disease in Asia with an estimated 140,000
      new infections annually the majority of which occurs in patients suffering from
      HIV/AIDS. Cryptococcus neoformans variety grubii (serotype A) is the major
      causative agent of this disease. In the present study, multilocus sequence typing
      (MLST) using the ISHAM MLST consensus scheme for the C. neoformans/C. gattii
      species complex was used to analyse nucleotide polymorphisms among 476 isolates
      of this pathogen obtained from 8 Asian countries. Population genetic analysis
      showed that the Asian C. neoformans var. grubii population shows limited genetic
      diversity and demonstrates a largely clonal mode of reproduction when compared
      with the global MLST dataset. HIV-status, sequence types and geography were found
      to be confounded. However, a correlation between sequence types and isolates from
      HIV-negative patients was observed among the Asian isolates. Observations of high
      gene flow between the Middle Eastern and the Southeastern Asian populations
      suggest that immigrant workers in the Middle East were originally infected in
      Southeastern Asia. 

PMID- 24019868
TI  - SCMCRYS: predicting protein crystallization using an ensemble scoring card method
      with estimating propensity scores of P-collocated amino acid pairs.
AB  - Existing methods for predicting protein crystallization obtain high accuracy
      using various types of complemented features and complex ensemble classifiers,
      such as support vector machine (SVM) and Random Forest classifiers. It is
      desirable to develop a simple and easily interpretable prediction method with
      informative sequence features to provide insights into protein crystallization.
      This study proposes an ensemble method, SCMCRYS, to predict protein
      crystallization, for which each classifier is built by using a scoring card
      method (SCM) with estimating propensity scores of p-collocated amino acid (AA)
      pairs (p=0 for a dipeptide). The SCM classifier determines the crystallization of
      a sequence according to a weighted-sum score. The weights are the composition of
      the p-collocated AA pairs, and the propensity scores of these AA pairs are
      estimated using a statistic with optimization approach. SCMCRYS predicts the
      crystallization using a simple voting method from a number of SCM classifiers.
      The experimental results show that the single SCM classifier utilizing dipeptide
      composition with accuracy of 73.90% is comparable to the best previously
      developed SVM-based classifier, SVM_POLY (74.6%), and our proposed SVM-based
      classifier utilizing the same dipeptide composition (77.55%). The SCMCRYS method
      with accuracy of 76.1% is comparable to the state-of-the-art ensemble methods
      PPCpred (76.8%) and RFCRYS (80.0%), which used the SVM and Random Forest
      classifiers, respectively. This study also investigates mutagenesis analysis
      based on SCM and the result reveals the hypothesis that the mutagenesis of
      surface residues Ala and Cys has large and small probabilities of enhancing
      protein crystallizability considering the estimated scores of crystallizability
      and solubility, melting point, molecular weight and conformational entropy of
      amino acids in a generalized condition. The propensity scores of amino acids and
      dipeptides for estimating the protein crystallizability can aid biologists in
      designing mutation of surface residues to enhance protein crystallizability. The
      source code of SCMCRYS is available at http://iclab.life.nctu.edu.tw/SCMCRYS/.

PMID- 24019869
TI  - Trametes versicolor protein YZP activates regulatory B lymphocytes - gene
      identification through de novo assembly and function analysis in a murine acute
      colitis model.
AB  - BACKGROUND: Trametes versicolor (Yun-Zhi) is a medicinal fungus used as a
      chemotherapy co-treatment to enhance anti-tumor immunity. Although the efficacies
      of T. versicolor extracts have been documented, the active ingredients and
      mechanisms underlying the actions of these extracts remain uncharacterized.
      RESULTS: We purified a new protein, YZP, from the fruiting bodies of T.
      versicolor and identified the gene encoding YZP using RNA-seq and de novo
      assembly technologies. YZP is a 12-kDa non-glycosylated protein comprising 139
      amino acids, including an 18-amino acids signal peptide. YZP induced a greater
      than 60-fold increase in IL-10 secretion in mice B lymphocytes; moreover, YZP
      specifically triggered the differentiation of CD1d(+) B cells into IL-10
      producing regulatory B cells (Bregs) and enhanced the expression of CD1d. YZP
      induced B cells suppressed approximately 40% of the LPS-activated macrophage
      production of inflammatory cytokines in a mixed leukocyte reaction and
      significantly alleviated the disease activity and colonic inflammation in a DSS
      induced acute colitis murine model. Furthermore, YZP activated Breg function via
      interaction with TLR2 and TLR4 and up-regulation of the TLR-mediated signaling
      pathway. CONCLUSIONS: We purified a novel Breg-stimulating protein, YZP, from T.
      versicolor and developed an advanced approach combining RNA-seq and de novo
      assembly technologies.to clone its gene. We demonstrated that YZP activated
      CD1d(+) Breg differentiation through TLR2/4-mediated signaling pathway, and the
      YZP-stimulated B cells exhibited anti-inflammatory efficacies in vitro and in
      murine acute colitis models.

PMID- 24019870
TI  - Dynamic transcript profiling of Candida albicans infection in zebrafish: a
      pathogen-host interaction study.
AB  - Candida albicans is responsible for a number of life-threatening infections and
      causes considerable morbidity and mortality in immunocompromised patients.
      Previous studies of C. albicans pathogenesis have suggested several steps must
      occur before virulent infection, including early adhesion, invasion, and late
      tissue damage. However, the mechanism that triggers C. albicans transformation
      from yeast to hyphae form during infection has yet to be fully elucidated. This
      study used a systems biology approach to investigate C. albicans infection in
      zebrafish. The surviving fish were sampled at different post-infection time
      points to obtain time-lapsed, genome-wide transcriptomic data from both
      organisms, which were accompanied with in sync histological analyses. Principal
      component analysis (PCA) was used to analyze the dynamic gene expression profiles
      of significant variations in both C. albicans and zebrafish. The results
      categorized C. albicans infection into three progressing phases: adhesion,
      invasion, and damage. Such findings were highly supported by the corresponding
      histological analysis. Furthermore, the dynamic interspecies transcript profiling
      revealed that C. albicans activated its filamentous formation during invasion and
      the iron scavenging functions during the damage phases, whereas zebrafish ceased
      its iron homeostasis function following massive hemorrhage during the later
      stages of infection. Most of the immune related genes were expressed as the
      infection progressed from invasion to the damage phase. Such global, inter
      species evidence of virulence-immune and iron competition dynamics during C.
      albicans infection could be crucial in understanding control fungal pathogenesis.

PMID- 24019871
TI  - Allometry and dissipation of ecological flow networks.
AB  - BACKGROUND: An ecological flow network is a weighted directed graph in which the
      nodes are species, the edges are "who eats whom" relationships and the weights
      are rates of energy or nutrient transferred between species. Allometric scaling
      is a ubiquitous feature for flow systems such as river basins, vascular networks
      and food webs. METHODOLOGY: The "ecological network analysis" can serve to reveal
      hidden allometries, the power law relationship between the throughflux and the
      indirect impact of node [Formula: see text], directly from the original flow
      networks without any need to cut edges in the network. The dissipation law, which
      is another significant scaling relationship between the energy dissipation
      (respiration) and the throughflow of any species, is also obtained from an
      analysis of the empirical flow networks. Interestingly, the exponents of the
      allometric law ([Formula: see text]) and the dissipation law ([Formula: see
      text]) show a strong relationship for both empirical and simulated flow networks.
      The dissipation law exponent [Formula: see text], rather than the topology of the
      network, is the most important factors that affect the allometric exponent
      [Formula: see text]. CONCLUSIONS: The exponent [Formula: see text] can be
      interpreted as the degree of centralization of the network, i.e., the
      concentration of impacts (direct and indirect influences on the entire network
      along all energy flow pathways) on hubs (the nodes with large throughflows). As a
      result, we find that as [Formula: see text] increases, the relative energy loss
      of large nodes increases, [Formula: see text] decreases, i.e., the relative
      importance of large species decreases. Moreover, the entire flow network is more
      decentralized. Therefore, network flow structure (allometry) and thermodynamic
      constraints (dissipation) are linked.

PMID- 24019872
TI  - The Hv-SGT1 gene from Haynaldia villosa contributes to resistances towards both
      biotrophic and hemi-biotrophic pathogens in common wheat (Triticum aestivum L.).
AB  - The SGT1 protein is essential for R protein-mediated and PAMPs-triggered
      resistance in many plant species. Here we reported the isolation and
      characterization of the Hv-SGT1 gene from Haynaldiavillosa (2n = 14, VV).
      Analysis of the subcellular location of Hv-SGT1 by transient expression of a
      fusion to GFP indicated its presence in the cytoplasm and nucleus. Levels of Hv
      SGT1 transcripts were increased by inoculation with either the biotrophic
      pathogen Blumeriagraminis DC. f. Sp. tritici (Bgt) or the hemi-biotrophic
      pathogen Fusariumgraminearum (Fg). Levels of Hv-SGT1 showed substantial increase
      following treatment with H2O2 and methyl jasmonate (MeJA), only slightly induced
      following exposure to ethephon or abscisic acid, but not changed following
      exposure to salicylic acid. The demonstration that silencing of Hv-SGT1
      substantially reduced resistance to Bgt indicated that Hv-SGT1 was an essential
      component of disease resistance in H. villosa. The over-expression of Hv-SGT1 in
      Yangmai 158 enhanced resistance to powdery mildew, and this correlated with
      increased levels of whole-cell reactive oxygen intermediates at the sites of
      penetration by the pathogens. Compared with wild-type plants, the expression
      levels of genes related to the H2O2 and JA signaling pathways were lower in the
      Hv-SGT1 silenced plants and higher in the Hv-SGT1 over-expressing plants.
      Therefore, the involvement of Hv-SGT1 in H2O2 production correlates with the
      hypersensitive response and jasmonic acid signaling. Our novel demonstration that
      wheat with over-expressed Hv-SGT1 showed enhanced resistance to both powdery
      mildew and FHB suggests that it could served as a transgenic genetic resource in
      wheat breeding for multiple disease resistance. 

PMID- 24019873
TI  - The latest succession of dinosaur tracksites in Europe: Hadrosaur ichnology,
      track production and palaeoenvironments.
AB  - A comprehensive review and study of the rich dinosaur track record of the Tremp
      Formation in the southern Pyrenees of Spain (Southwestern Europe) shows a unique
      succession of footprint localities prior to the end-Cretaceous mass extinction
      event. A description of some 30 new tracksites and data on sedimentary
      environments, track occurrence and preservation, ichnology and chronostratigraphy
      are provided. These new track localities represent various facies types within a
      diverse set of fluvial environments. The footprint discoveries mostly represent
      hadrosaurian and, less abundantly, to sauropod dinosaurs. The hadrosaur tracks
      are significantly smaller in size than, but morphologically similar to, those of
      North America and Asia and are attributable to the ichnogenus Hadrosauropodus.
      The track succession, with more than 40 distinct track levels, indicates that
      hadrosaur footprints in the Ibero-Armorican region occur predominantly in the
      late Maaastrichtian (at least above the early Maastrichtian-late Maastrichtian
      boundary). The highest abundance is found noticeably found in the late
      Maastrichtian, with tracks occurring in the C29r magnetochron, within about the
      latest 300,000 years of the Cretaceous. 

PMID- 24019874
TI  - Multiple amino acid sequence alignment nitrogenase component 1: insights into
      phylogenetics and structure-function relationships.
AB  - Amino acid residues critical for a protein's structure-function are retained by
      natural selection and these residues are identified by the level of variance in
      co-aligned homologous protein sequences. The relevant residues in the nitrogen
      fixation Component 1 alpha- and beta-subunits were identified by the alignment of
      95 protein sequences. Proteins were included from species encompassing multiple
      microbial phyla and diverse ecological niches as well as the nitrogen fixation
      genotypes, anf, nif, and vnf, which encode proteins associated with cofactors
      differing at one metal site. After adjusting for differences in sequence length,
      insertions, and deletions, the remaining >85% of the sequence co-aligned the
      subunits from the three genotypes. Six Groups, designated Anf, Vnf , and Nif I
      IV, were assigned based upon genetic origin, sequence adjustments, and conserved
      residues. Both subunits subdivided into the same groups. Invariant and single
      variant residues were identified and were defined as "core" for nitrogenase
      function. Three species in Group Nif-III, Candidatus Desulforudis audaxviator,
      Desulfotomaculum kuznetsovii, and Thermodesulfatator indicus, were found to have
      a seleno-cysteine that replaces one cysteinyl ligand of the 8Fe:7S, P-cluster.
      Subsets of invariant residues, limited to individual groups, were identified;
      these unique residues help identify the gene of origin (anf, nif, or vnf) yet
      should not be considered diagnostic of the metal content of associated cofactors.
      Fourteen of the 19 residues that compose the cofactor pocket are invariant or
      single variant; the other five residues are highly variable but do not correlate
      with the putative metal content of the cofactor. The variable residues are
      clustered on one side of the cofactor, away from other functional centers in the
      three dimensional structure. Many of the invariant and single variant residues
      were not previously recognized as potentially critical and their identification
      provides the bases for new analyses of the three-dimensional structure and for
      mutagenesis studies. 

PMID- 24019875
TI  - Comparing the happiness effects of real and on-line friends.
AB  - A recent large Canadian survey permits us to compare face-to-face ('real-life')
      and on-line social networks as sources of subjective well-being. The sample of
      5,000 is drawn randomly from an on-line pool of respondents, a group well placed
      to have and value on-line friendships. We find three key results. First, the
      number of real-life friends is positively correlated with subjective well-being
      (SWB) even after controlling for income, demographic variables and personality
      differences. Doubling the number of friends in real life has an equivalent effect
      on well-being as a 50% increase in income. Second, the size of online networks is
      largely uncorrelated with subjective well-being. Third, we find that real-life
      friends are much more important for people who are single, divorced, separated or
      widowed than they are for people who are married or living with a partner.
      Findings from large international surveys (the European Social Surveys 2002-2008)
      are used to confirm the importance of real-life social networks to SWB; they also
      indicate a significantly smaller value of social networks to married or partnered
      couples. 

PMID- 24019876
TI  - Insectivorous bats digest chitin in the stomach using acidic mammalian chitinase.
AB  - The gastrointestinal tract of animals is adapted to their primary source of food
      to optimize resource use and energy intake. Temperate bat species mainly feed on
      arthropods. These contain the energy-rich carbohydrate chitin, which is
      indigestible for the endogenous enzymes of a typical mammalian gastrointestinal
      tract. However, the gastrointestinal tract of bat species should be adapted to
      their diet and be able to digest chitin. We hypothesized that (i) European
      vespertilionid bat species have the digestive enzyme chitinase and that (ii) the
      chitinolytic activity is located in the intestine, as has been found for North
      American bat species. The gastrointestinal tracts of seven bat species
      (Pipistrellus pipistrellus, Plecotus auritus, Myotis bechsteinii, Myotis
      nattereri, Myotis daubentonii, Myotis myotis, and Nyctalus leisleri) were tested
      for chitinolytic activity by diffusion assay. Gastrointestinal tracts of P.
      pipistrellus, P. auritus, M. nattereri, M. myotis, and N. leisleri were examined
      for acidic mammalian chitinase by western blot analysis. Tissue sections of the
      gastrointestinal tract of P. pipistrellus were immunohistochemically analyzed to
      locate the acidic mammalian chitinase. Chitinolytic activity was detected in the
      stomachs of all bat species. Western blot analysis confirmed the acidic mammalian
      chitinase in stomach samples. Immunohistochemistry of the P. pipistrellus
      gastrointestinal tract indicated that acidic mammalian chitinase is located in
      the stomach chief cells at the base of the gastric glands. In conclusion,
      European vespertilionid bat species have acidic mammalian chitinase that is
      produced in the gastric glands of the stomach. Therefore, the gastrointestinal
      tracts of insectivorous bat species evolved an enzymatic adaptation to their
      diet. 

PMID- 24019877
TI  - Nitric oxide acts as a positive regulator to induce metamorphosis of the ascidian
      Herdmania momus.
AB  - Marine invertebrates commonly have a biphasic life cycle in which the metamorphic
      transition from a pelagic larva to a benthic post-larva is mediated by the nitric
      oxide signalling pathway. Nitric oxide (NO) is synthesised by nitric oxide
      synthase (NOS), which is a client protein of the molecular chaperon heat shock
      protein 90 (HSP90). It is notable, then, that both NO and HSP90 have been
      implicated in regulating metamorphosis in marine invertebrates as diverse as
      urochordates, echinoderms, molluscs, annelids, and crustaceans. Specifically, the
      suppression of NOS activity by the application of either NOS- or HSP90-inhibiting
      pharmacological agents has been shown consistently to induce the initiation of
      metamorphosis, leading to the hypothesis that a negative regulatory role of NO is
      widely conserved in biphasic life cycles. Further, the induction of metamorphosis
      by heat-shock has been demonstrated for multiple species. Here, we investigate
      the regulatory role of NO in induction of metamorphosis of the solitary tropical
      ascidian, Herdmania momus. By coupling pharmacological treatments with analysis
      of HmNOS and HmHSP90 gene expression, we present compelling evidence of a
      positive regulatory role for NO in metamorphosis of this species, in contrast to
      all existing ascidian data that supports the hypothesis of NO as a conserved
      negative regulator of metamorphosis. The exposure of competent H. momus larvae to
      a NOS inhibitor or an NO donor results in an up-regulation of NOS and HSP90
      genes. Heat shock of competent larvae induces metamorphosis in a temperature
      dependent manner, up to a thermal tolerance that approaches 35 degrees C. Both
      larval/post-larval survival and the appearance of abnormal morphologies in H.
      momus post-larvae reflect the magnitude of up-regulation of the HSP90 gene in
      response to heat-shock. The demonstrated role of NO as a positive metamorphic
      regulator in H. momus suggests the existence of inter-specific adaptations of NO
      regulation in ascidian metamorphosis. 

PMID- 24019878
TI  - Antidepressant-like effects of erythropoietin: a focus on behavioural and
      hippocampal processes.
AB  - Depression is a chronic and debilitating condition with a significant degree of
      relapse and treatment resistance that could stem, at least in part, from
      disturbances of neuroplasticity. This has led to an increased focus on treatment
      strategies that target brain derived neurotrophic factor (BDNF), synaptic
      plasticity and adult neurogenesis. In the current study we aimed to assess
      whether erythropoietin (EPO) would have antidepressant-like effects given its
      already established pro-trophic actions. In particular, we assessed whether EPO
      would diminish the deleterious effects of a social stressor in mice. Indeed, EPO
      induced anxiolytic and antidepressant-like responses in a forced swim test, open
      field, elevated-plus maze, and a novelty test, and appeared to blunt some of the
      negative behavioural effects of a social stressor. Furthermore, EPO promoted
      adult hippocampal neurogenesis, an important feature of effective
      antidepressants. Finally, a separate study using the mTOR inhibitor rapamycin
      revealed that antagonizing this pathway prevented the impact of EPO upon forced
      swim performance. These data are consistent with previous findings showing that
      the mTOR pathway and its neurogenic and synaptogenic effects might mediate the
      behavioral consequences of antidepressant agents. Our findings further highlight
      EPO as a possible adjunct treatment for affective disorders, as well as other
      stressor associated disorders of impaired neuroplasticity. 

PMID- 24019879
TI  - Relationships among traits of aerobic and anaerobic swimming performance in
      individual European sea bass Dicentrarchus labrax.
AB  - Teleost fishes exhibit wide and temporally stable inter-individual variation in a
      suite of aerobic and anaerobic locomotor traits. One mechanism that could allow
      such variation to persist within populations is the presence of tradeoffs between
      aerobic and anaerobic performance, such that individuals with a high capacity for
      one type of performance have a reduced capacity for the other. We investigated
      this possibility in European seabass Dicentrarchuslabrax, each measured for a
      battery of indicators of maximum locomotor performance. Aerobic traits comprised
      active metabolic rate, aerobic scope for activity, maximum aerobic swimming
      speed, and stride length, using a constant acceleration test. Anaerobic traits
      comprised maximum speed during an escape response, maximum sprint speed, and
      maximum anaerobic burst speed during constant acceleration. The data provided
      evidence of significant variation in performance among individuals, but there was
      no evidence of any trade-offs among any traits of aerobic versus anaerobic
      swimming performance. Furthermore, the anaerobic traits were not correlated
      significantly among each other, despite relying on the same muscular structures.
      Thus, the variation observed may reflect trade-offs with other morphological,
      physiological or behavioural traits. 

PMID- 24019880
TI  - FGF-23 regulates CYP27B1 transcription in the kidney and in extra-renal tissues.
AB  - The mitochondrial enzyme 25-hydroxyvitamin D 1alpha-hydroxylase, which is encoded
      by the CYP27B1 gene, converts 25OHD to the biological active form of vitamin D,
      1,25-dihydroxyvitamin D (1,25(OH)2D). Renal 1alpha-hydroxylase activity is the
      principal determinant of the circulating 1,25(OH)2D concentration and enzyme
      activity is tightly regulated by several factors. Fibroblast growth factor-23
      (FGF-23) decreases serum 1,25(OH)2D concentrations by suppressing CYP27B1 mRNA
      abundance in mice. In extra-renal tissues, 1alpha-hydroxylase is responsible for
      local 1,25(OH)2D synthesis, which has important paracrine actions, but whether
      FGF-23 regulates CYP27B1 gene expression in extra-renal tissues is unknown. We
      sought to determine whether FGF-23 regulates CYP27B1 transcription in the kidney
      and whether extra-renal tissues are target sites for FGF-23-induced suppression
      of CYP27B1. In HEK293 cells transfected with the human CYP27B1 promoter, FGF-23
      suppressed promoter activity by 70%, and the suppressive effect was blocked by CI
      1040, a specific inhibitor of extracellular signal regulated kinase 1/2. To
      examine CYP27B1 transcriptional activity in vivo, we crossed fgf-23 null mice
      with mice bearing the CYP27B1 promoter-driven luciferase transgene (1alpha-Luc).
      In the kidney of FGF-23 null/1alpha-Luc mice, CYP27B1 promoter activity was
      increased by 3-fold compared to that in wild-type/1alpha-Luc mice.
      Intraperitoneal injection of FGF-23 suppressed renal CYP27B1 promoter activity
      and protein expression by 26% and 60% respectively, and the suppressive effect
      was blocked by PD0325901, an ERK1/2 inhibitor. These findings provide evidence
      that FGF-23 suppresses CYP27B1 transcription in the kidney. Furthermore, we
      demonstrate that in FGF-23 null/1alpha-Luc mice, CYP27B1 promoter activity and
      mRNA abundance are increased in several extra-renal sites. In the heart of FGF-23
      null/1alpha-Luc mice, CYP27B1 promoter activity and mRNA were 2- and 5-fold
      higher, respectively, than in control mice. We also observed a 3- to 10-fold
      increase in CYP27B1 mRNA abundance in the lung, spleen, aorta and testis of FGF
      23 null/1alpha-Luc mice. Thus, we have identified novel extra-renal target sites
      for FGF-23-mediated regulation of CYP27B1. 

PMID- 24019881
TI  - Predicting binding within disordered protein regions to structurally
      characterised peptide-binding domains.
AB  - Disordered regions of proteins often bind to structured domains, mediating
      interactions within and between proteins. However, it is difficult to identify a
      priori the short disordered regions involved in binding. We set out to determine
      if docking such peptide regions to peptide binding domains would assist in these
      predictions.We assembled a redundancy reduced dataset of SLiM (Short Linear
      Motif) containing proteins from the ELM database. We selected 84 sequences which
      had an associated PDB structures showing the SLiM bound to a protein receptor,
      where the SLiM was found within a 50 residue region of the protein sequence which
      was predicted to be disordered. First, we investigated the Vina docking scores of
      overlapping tripeptides from the 50 residue SLiM containing disordered regions of
      the protein sequence to the corresponding PDB domain. We found only weak
      discrimination of docking scores between peptides involved in binding and
      adjacent non-binding peptides in this context (AUC 0.58).Next, we trained a
      bidirectional recurrent neural network (BRNN) using as input the protein
      sequence, predicted secondary structure, Vina docking score and predicted
      disorder score. The results were very promising (AUC 0.72) showing that multiple
      sources of information can be combined to produce results which are clearly
      superior to any single source.We conclude that the Vina docking score alone has
      only modest power to define the location of a peptide within a larger protein
      region known to contain it. However, combining this information with other
      knowledge (using machine learning methods) clearly improves the identification of
      peptide binding regions within a protein sequence. This approach combining
      docking with machine learning is primarily a predictor of binding to peptide
      binding sites, and is not intended as a predictor of specificity of binding to
      particular receptors. 

PMID- 24019882
TI  - Principles of regulation of self-renewing cell lineages.
AB  - Identifying the exact regulatory circuits that can stably maintain tissue
      homeostasis is critical for our basic understanding of multicellular organisms,
      and equally critical for identifying how tumors circumvent this regulation, thus
      providing targets for treatment. Despite great strides in the understanding of
      the molecular components of stem-cell regulation, the overall mechanisms
      orchestrating tissue homeostasis are still far from being understood. Typically,
      tissue contains the stem cells, transit amplifying cells, and terminally
      differentiated cells. Each of these cell types can potentially secrete regulatory
      factors and/or respond to factors secreted by other types. The feedback can be
      positive or negative in nature. This gives rise to a bewildering array of
      possible mechanisms that drive tissue regulation. In this paper, we propose a
      novel method of studying stem cell lineage regulation, and identify possible
      numbers, types, and directions of control loops that are compatible with
      stability, keep the variance low, and possess a certain degree of robustness. For
      example, there are exactly two minimal (two-loop) control networks that can
      regulate two-compartment (stem and differentiated cell) tissues, and 20 such
      networks in three-compartment tissues. If division and differentiation decisions
      are coupled, then there must be a negative control loop regulating divisions of
      stem cells (e.g. by means of contact inhibition). While this mechanism is
      associated with the highest robustness, there could be systems that maintain
      stability by means of positive divisions control, coupled with specific types of
      differentiation control. Some of the control mechanisms that we find have been
      proposed before, but most of them are new, and we describe evidence for their
      existence in data that have been previously published. By specifying the types of
      feedback interactions that can maintain homeostasis, our mathematical analysis
      can be used as a guide to experimentally zero in on the exact molecular
      mechanisms in specific tissues. 

PMID- 24019883
TI  - Simulating polar bear energetics during a seasonal fast using a mechanistic
      model.
AB  - In this study we tested the ability of a mechanistic model (Niche MapperTM) to
      accurately model adult, non-denning polar bear (Ursus maritimus) energetics while
      fasting during the ice-free season in the western Hudson Bay. The model uses a
      steady state heat balance approach, which calculates the metabolic rate that will
      allow an animal to maintain its core temperature in its particular microclimate
      conditions. Predicted weight loss for a 120 day fast typical of the 1990s was
      comparable to empirical studies of the population, and the model was able to
      reach a heat balance at the target metabolic rate for the entire fast, supporting
      use of the model to explore the impacts of climate change on polar bears. Niche
      Mapper predicted that all but the poorest condition bears would survive a 120 day
      fast under current climate conditions. When the fast extended to 180 days, Niche
      Mapper predicted mortality of up to 18% for males. Our results illustrate how
      environmental conditions, variation in animal properties, and thermoregulation
      processes may impact survival during extended fasts because polar bears were
      predicted to require additional energetic expenditure for thermoregulation during
      a 180 day fast. A uniform 3 degrees C temperature increase reduced male mortality
      during a 180 day fast from 18% to 15%. Niche Mapper explicitly links an animal's
      energetics to environmental conditions and thus can be a valuable tool to help
      inform predictions of climate-related population changes. Since Niche Mapper is a
      generic model, it can make energetic predictions for other species threatened by
      climate change. 

PMID- 24019884
TI  - Discovery of novel Bmy1 alleles increasing beta-amylase activity in Chinese
      landraces and Tibetan wild barley for improvement of malting quality via MAS.
AB  - China has a large barley germplasm collection which has not been well
      characterized and is therefore underutilized. The Bmy1 locus encoding the beta
      amylase enzyme on chromosome 4H has been well characterized in the worldwide
      barley germplasm collections due to its importance in the malting and brewing
      industry. The Bmy1 locus was chosen as an indicator to understand genetic
      potential for improvement of malting quality in Chinese landraces and Tibetan
      wild barley. The genetic diversity of 91 barley accessions was assessed using
      allele specific Multiplex-ready molecular markers. Eight accessions were further
      sequenced, based on the Multiplex-ready marker diversity for Bmy1 in the
      germplasm. Six of the eight accessions clustered together in a unique group, and
      showed similarities to 'Haruna Nijo', wild barley accession PI296896 and
      'Ashqelon'. Sequence comparisons with the known Bmy1 alleles identified not only
      the existing 13 amino acid substitutions, but also a new substitution positioned
      at A387T from a Chinese landrace W127, which has the highest beta-amylase
      activity. Two new alleles/haplotypes namely Bmy1-Sd1c and Bmy1-Sd5 were
      designated based on different amino acid combinations. We identified new amino
      acid combination of C115, D165, V233, S347 and V430 in the germplasm. The broad
      variation in both beta-amylase activity and amino acid composition provides novel
      alleles for the improvement of malting quality for different brewing styles,
      which indicates the high potential value of the Chinese landraces and Tibetan
      wild barley. 

PMID- 24019885
TI  - Pertussis toxin B-pentamer mediates intercellular transfer of membrane proteins
      and lipids.
AB  - Pertussis toxin (PTx) is the major virulence factor of Bordetella pertussis. The
      enzymatic or active (A) subunit inactivates host G protein coupled receptor
      (GPCR) signaling pathways. The non-enzymatic binding (B) subunit also mediates
      biological effects due to lectin-like binding characteristics, including the
      induction of T cell receptor (TCR) signaling and subsequent down-regulation of
      chemokine receptor expression. Here we report another activity attributable to
      PTxB, facilitating transfer of membrane material between mammalian cells. This
      activity does not require the TCR, and does not require cell-to-cell contact or
      cellular aggregation. Rather, membrane vesicles are transferred from donor to
      recipient cells in a toxin-dependent fashion. Membrane transfer occurs in
      different cell types, including cultured human T cells, CHO cells, and human
      primary peripheral blood mononuclear cells. Transfer involves both lipid and
      integral membrane proteins, as evidenced by the transfer of T and B cell-specific
      receptor molecules to other PBMCs. Interestingly, membrane transfer activity is a
      property that PTx shares with some, but not all, cell-aggregating lectins that
      are mitogenic for human T cells, and appears to be related to the ability to bind
      certain host cell glycolipids. This phenomenon may represent another mechanism by
      which pertussis toxin disrupts mammalian intra- and inter-cellular signaling. 

PMID- 24019886
TI  - Sympathetic nervous system catecholamines and neuropeptide Y neurotransmitters
      are upregulated in human NAFLD and modulate the fibrogenic function of hepatic
      stellate cells.
AB  - BACKGROUND: Sympathetic nervous system (SNS) signalling regulates murine hepatic
      fibrogenesis through effects on hepatic stellate cells (HSC), and obesity-related
      hypertension with SNS activation accelerates progression of non-alcoholic fatty
      liver disease (NAFLD), the commonest cause of chronic liver disease. NAFLD may
      lead to cirrhosis. The effects of the SNS neurotransmitters norepinephrine (NE),
      epinephrine (EPI) and neuropeptide Y (NPY) on human primary HSC (hHSC) function
      and in NAFLD pathogenesis are poorly understood. AIMS: to determine the
      mechanistic effects of NE/EPI/NPY on phenotypic changes in cultured hHSC, and to
      study SNS signalling in human NAFLD livers. METHODS: Freshly isolated hHSC were
      assessed for expression of cathecholamine/neuropeptide Y receptors and for the
      synthesis of NE/EPI. The effects of NE/EPI/NPY and adrenoceptor antagonists
      prazosin (PRZ)/propranolol (PRL) on hHSC fibrogenic functions and the involved
      kinases and interleukin pathways were examined. Human livers with proven NAFLD
      were then assessed for upregulation of SNS signalling components. RESULTS:
      Activated hHSC express functional alpha/beta-adrenoceptors and NPY receptors,
      which are upregulated in the livers of patients with cirrhotic NAFLD. hHSC in
      culture synthesize and release NE/EPI, required for their optimal basal growth
      and survival. Exogenous NE/EPI and NPY dose-dependently induced hHSC
      proliferation, mediated via p38 MAP, PI3K and MEK signalling. NE and EPI but not
      NPY increased expression of collagen-1alpha2 via TGF-beta without involvement of
      the pro-fibrogenic cytokines leptin, IL-4 and IL-13 or the anti-fibrotic cytokine
      IL-10. CONCLUSIONS: hHSC synthesize and require cathecholamines for optimal
      survival and fibrogenic functionality. Activated hHSC express directly fibrogenic
      alpha/beta-adrenoceptors and NPY receptors, upregulated in human cirrhotic NAFLD.
      Adrenoceptor and NPY antagonists may be novel anti-fibrotic agents in human
      NAFLD.

PMID- 24019888
TI  - The response of aboveground net primary productivity of desert vegetation to
      rainfall pulse in the temperate desert region of northwest China.
AB  - Rainfall events can be characterized as "pulses", which are discrete and variable
      episodes that can significantly influence the structure and function of desert
      ecosystems, including shifts in aboveground net primary productivity (ANPP). To
      determine the threshold and hierarchical response of rainfall event size on the
      Normalized Difference Vegetation Index (NDVI, a proxy for ANPP) and the
      difference across a desert area in northwestern China with two habitats - dune
      and desert - we selected 17 independent summer rainfall events from 2005 to 2012,
      and obtained a corresponding NDVI dataset extracted from MODIS images. Based on
      the threshold-delay model and statistical analysis, the results showed that the
      response of NDVI to rainfall pulses began at about a 5 mm event size.
      Furthermore, when the rainfall event size was more than 30 mm, NDVI rapidly
      increased 3- to 6-fold compared with the response to events of less than 30 mm,
      suggesting that 30 mm was the threshold for a large NDVI response. These results
      revealed the importance of the 5 mm and 30 mm rainfall events for plant survival
      and growth in desert regions. There was an 8- to 16-day lag time between the
      rainfall event and the NDVI response, and the response duration varied with
      rainfall event size, reaching a maximum of 32 days. Due to differences in soil
      physical and mineralogical properties, and to biodiversity structure and the root
      systems' abilities to exploit moisture, dune and desert areas differed in
      precipitation responses: dune habitats were characterized by a single, late
      summer productivity peak; in contrast, deserts showed a multi-peak pattern
      throughout the growing season. 

PMID- 24019889
TI  - Diffusion weighted image denoising using overcomplete local PCA.
AB  - Diffusion Weighted Images (DWI) normally shows a low Signal to Noise Ratio (SNR)
      due to the presence of noise from the measurement process that complicates and
      biases the estimation of quantitative diffusion parameters. In this paper, a new
      denoising methodology is proposed that takes into consideration the
      multicomponent nature of multi-directional DWI datasets such as those employed in
      diffusion imaging. This new filter reduces random noise in multicomponent DWI by
      locally shrinking less significant Principal Components using an overcomplete
      approach. The proposed method is compared with state-of-the-art methods using
      synthetic and real clinical MR images, showing improved performance in terms of
      denoising quality and estimation of diffusion parameters. 

PMID- 24019887
TI  - Integrated analysis of global mRNA and protein expression data in HEK293 cells
      overexpressing PRL-1.
AB  - BACKGROUND: The protein tyrosine phosphatase PRL-1 represents a putative oncogene
      with wide-ranging cellular effects. Overexpression of PRL-1 can promote cell
      proliferation, survival, migration, invasion, and metastasis, but the underlying
      mechanisms by which it influences these processes remain poorly understood.
      METHODOLOGY: To increase our comprehension of PRL-1 mediated signaling events, we
      employed transcriptional profiling (DNA microarray) and proteomics (mass
      spectrometry) to perform a thorough characterization of the global molecular
      changes in gene expression that occur in response to stable PRL-1 overexpression
      in a relevant model system (HEK293). PRINCIPAL FINDINGS: Overexpression of PRL-1
      led to several significant changes in the mRNA and protein expression profiles of
      HEK293 cells. The differentially expressed gene set was highly enriched in genes
      involved in cytoskeletal remodeling, integrin-mediated cell-matrix adhesion, and
      RNA recognition and splicing. In particular, members of the Rho signaling pathway
      and molecules that converge on this pathway were heavily influenced by PRL-1
      overexpression, supporting observations from previous studies that link PRL-1 to
      the Rho GTPase signaling network. In addition, several genes not previously
      associated with PRL-1 were found to be significantly altered by its expression.
      Most notable among these were Filamin A, RhoGDIalpha, SPARC, hnRNPH2, and PRDX2.
      CONCLUSIONS AND SIGNIFICANCE: This systems-level approach sheds new light on the
      molecular networks underlying PRL-1 action and presents several novel directions
      for future, hypothesis-based studies.

PMID- 24019890
TI  - Kallikrein gene-modified EPCs induce angiogenesis in rats with ischemic hindlimb
      and correlate with integrin alphavbeta3 expression.
AB  - BACKGROUND: Human tissue kallikrein (hTK) plays an essential role in the
      physiological and pathological mechanisms of blood vessels. This study aimed to
      determine whether angiogenesis induced by endothelial progenitor cells (EPCs)
      transduced with the adenovirus-mediated hTK gene could improve blood flow in rat
      hindlimb ischemia in vivo and to establish a promising mechanism in vitro.
      METHODS: EPCs transduced with adenovirus encoding hTK-162 (i.e., Ad/hTK
      transduced EPCs or Ad/GFP-transduced EPCs) were administered to Wister rats with
      hindlimb ischemia through therapeutic neovascularization. Muscular capillary
      density (MCD), blood flow (BF), and the number of myofibers were measured at days
      7, 14, and 21 after treatment. Expressions of integrin alphavbeta3 and
      endothelial nitric oxide synthase (eNOS) were detected on the surface of EPCs.
      RESULTS: MCD, BF, and the number of myofibers in rats with Ad/hTK-transduced EPCs
      remarkably increased at day 21 after treatment compared with rats with Ad/GFP
      transduced EPCs or the control group (P<0.01). Expressions of integrin
      alphavbeta3 and eNOS protein on the surface of EPCs also increased in rats with
      Ad/hTK-transduced EPCs. The levels of integrin alphavbeta3 expression were
      reduced by PI3K and eNOS blockade, and the inhibitor of integrin alphavbeta3
      abrogated the migration and adhesion of hTK-transduced EPCs (P<0.05). CONCLUSION:
      hTK gene delivery in vivo improves the natural angiogenic response to ischemia.
      The ability of hTK gene-transduced EPCs can be enhanced in vitro, in which
      integrin alphavbeta3 plays a role in the process.

PMID- 24019892
TI  - marmap: A package for importing, plotting and analyzing bathymetric and
      topographic data in R.
AB  - In this communication we introduce marmap, a package designed for downloading,
      plotting and manipulating bathymetric and topographic data in R. marmap can query
      the ETOPO1 bathymetry and topography database hosted by the NOAA, use simple
      latitude-longitude-depth data in ascii format, and take advantage of the advanced
      plotting tools available in R to build publication-quality bathymetric maps.
      Functions to query data (bathymetry, sampling information...) are available
      interactively by clicking on marmap maps. Bathymetric and topographic data can
      also be used to calculate projected surface areas within specified depth/altitude
      intervals, and constrain the calculation of realistic shortest path distances.
      Such information can be used in molecular ecology, for example, to evaluate
      genetic isolation by distance in a spatially-explicit framework. 

PMID- 24019891
TI  - Acute maternal infection and risk of pre-eclampsia: a population-based case
      control study.
AB  - BACKGROUND: Infection in pregnancy may be involved in the aetiology of pre
      eclampsia. However, a clear association between acute maternal infection and pre
      eclampsia has not been established. We assessed whether acute urinary tract
      infection, respiratory tract infection, and antibiotic drug prescriptions in
      pregnancy (a likely proxy for maternal infection) are associated with an
      increased risk of pre-eclampsia. METHODS AND FINDINGS: We used a matched nested
      case-control design and data from the UK General Practice Research Database to
      examine the association between maternal infection and pre-eclampsia. Primiparous
      women aged at least 13 years and registered with a participating practice between
      January 1987 and October 2007 were eligible for inclusion. We selected all cases
      of pre-eclampsia and a random sample of primiparous women without pre-eclampsia
      (controls). Cases (n=1533) were individually matched with up to ten controls
      (n=14236) on practice and year of delivery. We calculated odds ratios and 95%
      confidence intervals for pre-eclampsia comparing women exposed and unexposed to
      infection using multivariable conditional logistic regression. After adjusting
      for maternal age, pre-gestational hypertension, diabetes, renal disease and
      multifetal gestation, the odds of pre-eclampsia were increased in women
      prescribed antibiotic drugs (adjusted odds ratio 1.28;1.14-1.44) and in women
      with urinary tract infection (adjusted odds ratio 1.22;1.03-1.45). We found no
      association with maternal respiratory tract infection (adjusted odds ratio
      0.91;0.72-1.16). Further adjustment for maternal smoking and pre-pregnancy body
      mass index made no difference to our findings. CONCLUSIONS: Women who acquire a
      urinary infection during pregnancy, but not those who have a respiratory
      infection, are at an increased risk of pre-eclampsia. Maternal antibiotic
      prescriptions are also associated with an increased risk. Further research is
      required to elucidate the underlying mechanism of this association and to
      determine whether, among women who acquire infections in pregnancy, prompt
      treatment or prophylaxis against infection might reduce the risk of pre
      eclampsia.

PMID- 24019893
TI  - The investment in scent: time-resolved metabolic processes in developing volatile
      producing Nigella sativa L. seeds.
AB  - The interplay of processes in central and specialized metabolisms during seed
      development of Nigella sativa L. was studied by using a high-throughput
      metabolomics technology and network-based analysis. Two major metabolic shifts
      were identified during seed development: the first was characterized by the
      accumulation of storage lipids (estimated as total fatty acids) and N-compounds,
      and the second by the biosynthesis of volatile organic compounds (VOCs) and a 30%
      average decrease in total fatty acids. Network-based analysis identified
      coordinated metabolic processes during development and demonstrated the presence
      of five network communities. Enrichment analysis indicated that different
      compound classes, such as sugars, amino acids, and fatty acids, are largely
      separated and over-represented in certain communities. One community displayed
      several terpenoids and the central metabolites, shikimate derived amino acids,
      raffinose, xylitol and glycerol-3-phosphate. The latter are related to precursors
      of the mevalonate-independent pathway for VOC production in the plastid; also
      plastidial fatty acid 18?3n-3 abundant in "green" seeds grouped with several
      major terpenes. The findings highlight the interplay between the components of
      central metabolism and the VOCs. The developmental regulation of Nigella seed
      metabolism during seed maturation suggests a substantial re-allocation of carbon
      from the breakdown of fatty acids and from N-compounds, probably towards the
      biosynthesis of VOCs.

PMID- 24019894
TI  - p21-Activated kinase (PAK) regulates cytoskeletal reorganization and directional
      migration in human neutrophils.
AB  - Neutrophils serve as a first line of defense in innate immunity owing in part to
      their ability to rapidly migrate towards chemotactic factors derived from
      invading pathogens. As a migratory function, neutrophil chemotaxis is regulated
      by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases
      orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In
      this study, we characterized the role of p21-activated kinase (PAK) downstream of
      Rho GTPases in cytoskeletal remodeling and chemotactic processes of human
      neutrophils. We found that PAK activation occurred upon stimulation of
      neutrophils with f-Met-Leu-Phe (fMLP), and PAK accumulated at the actin-rich
      leading edge of stimulated neutrophils, suggesting a role for PAK in Rac
      dependent actin remodeling. Treatment with the pharmacological PAK inhibitor,
      PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and
      surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil
      morphological polarization and directional migration under a gradient of fMLP,
      and was associated with dysregulated Ca(2+) signaling. These results suggest that
      PAK serves as an important effector of Rho-family GTPases in neutrophil
      cytoskeletal reorganization, and plays a key role in driving efficient
      directional migration of human neutrophils. 

PMID- 24019895
TI  - Mining RNA-seq data for infections and contaminations.
AB  - RNA sequencing (RNA-seq) provides novel opportunities for transcriptomic studies
      at nucleotide resolution, including transcriptomics of viruses or microbes
      infecting a cell. However, standard approaches for mapping the resulting
      sequencing reads generally ignore alternative sources of expression other than
      the host cell and are little equipped to address the problems arising from
      redundancies and gaps among sequenced microbe and virus genomes. We show that
      screening of sequencing reads for contaminations and infections can be performed
      easily using ContextMap, our recently developed mapping software. Based on
      mapping-derived statistics, mapping confidence, similarities and
      misidentifications (e.g. due to missing genome sequences) of species/strains can
      be assessed. Performance of our approach is evaluated on three real-life
      sequencing data sets and compared to state-of-the-art metagenomics tools. In
      particular, ContextMap vastly outperformed GASiC and GRAMMy in terms of runtime.
      In contrast to MEGAN4, it was capable of providing individual read mappings to
      species and resolving non-unique mappings, thus allowing the identification of
      misalignments caused by sequence similarities between genomes and missing genome
      sequences. Our study illustrates the importance and potentials of routinely
      mining RNA-seq experiments for infections or contaminations by microbes and
      viruses. By using ContextMap, gene expression of infecting agents can be analyzed
      and novel insights in infection processes and tumorigenesis can be obtained. 

PMID- 24019896
TI  - Network and data integration for biomarker signature discovery via network
      smoothed T-statistics.
AB  - Predictive, stable and interpretable gene signatures are generally seen as an
      important step towards a better personalized medicine. During the last decade
      various methods have been proposed for that purpose. However, one important
      obstacle for making gene signatures a standard tool in clinics is the typical low
      reproducibility of signatures combined with the difficulty to achieve a clear
      biological interpretation. For that purpose in the last years there has been a
      growing interest in approaches that try to integrate information from molecular
      interaction networks. We here propose a technique that integrates network
      information as well as different kinds of experimental data (here exemplified by
      mRNA and miRNA expression) into one classifier. This is done by smoothing t
      statistics of individual genes or miRNAs over the structure of a combined protein
      protein interaction (PPI) and miRNA-target gene network. A permutation test is
      conducted to select features in a highly consistent manner, and subsequently a
      Support Vector Machine (SVM) classifier is trained. Compared to several other
      competing methods our algorithm reveals an overall better prediction performance
      for early versus late disease relapse and a higher signature stability. Moreover,
      obtained gene lists can be clearly associated to biological knowledge, such as
      known disease genes and KEGG pathways. We demonstrate that our data integration
      strategy can improve classification performance compared to using a single data
      source only. Our method, called stSVM, is available in R-package netClass on CRAN
      (http://cran.r-project.org). 

PMID- 24019897
TI  - Distinct internalization pathways of human amylin monomers and its cytotoxic
      oligomers in pancreatic cells.
AB  - Toxic human amylin oligomers and aggregates are implicated in the pathogenesis of
      type 2 diabetes mellitus (TTDM). Although recent studies have shown that
      pancreatic cells can recycle amylin monomers and toxic oligomers, the exact
      uptake mechanism and trafficking routes of these molecular forms and their
      significance for amylin toxicity are yet to be determined. Using pancreatic rat
      insulinoma (RIN-m5F) beta (beta)-cells and human islets as model systems we show
      that monomers and oligomers cross the plasma membrane (PM) through both
      endocytotic and non-endocytotic (translocation) mechanisms, the predominance of
      which is dependent on amylin concentrations and incubation times. At low (<= 100
      nM) concentrations, internalization of amylin monomers in pancreatic cells is
      completely blocked by the selective amylin-receptor (AM-R) antagonist, AC-187,
      indicating an AM-R dependent mechanism. In contrast at cytotoxic (uM)
      concentrations monomers initially (1 hour) enter pancreatic cells by two distinct
      mechanisms: translocation and macropinocytosis. However, during the late stage
      (24 hours) monomers internalize by a clathrin-dependent but AM-R and
      macropinocytotic independent pathway. Like monomers a small fraction of the
      oligomers initially enter cells by a non-endocytotic mechanism. In contrast a
      majority of the oligomers at both early (1 hour) and late times (24 hours)
      traffic with a fluid-phase marker, dextran, to the same endocytotic compartments,
      the uptake of which is blocked by potent macropinocytotic inhibitors. This led to
      a significant increase in extra-cellular PM accumulation, in turn potentiating
      amylin toxicity in pancreatic cells. Our studies suggest that macropinocytosis is
      a major but not the only clearance mechanism for both amylin's molecular forms,
      thereby serving a cyto-protective role in these cells.

PMID- 24019899
TI  - Circulating microparticles from Crohn's disease patients cause endothelial and
      vascular dysfunctions.
AB  - BACKGROUND: Microparticles (MPs) are small vesicles released during cell
      activation or apoptosis. They are involved in coagulation, inflammation and
      vascular dysfunction in several diseases. We characterized circulating MPs from
      Crohn's Disease (CD) patients and evaluated their effects on endothelial function
      and vascular reactivity after in vivo injection into mice. METHODS: Circulating
      MPs and their cellular origins were examined by flow cytometry from blood samples
      from healthy subjects (HS) and inactive or active CD patients. MPs were
      intravenously injected into mice. After 24 hours, endothelial function and
      vascular reactivity were assessed. RESULTS: Circulating MP levels did not differ
      between HS and inactive CD patients except for an increase in leukocyte-derived
      MPs in CD. Active CD patients compared to HS displayed increased total
      circulating MPs, pro-coagulant MPs and those from platelets, endothelium,
      erythrocytes, leukocytes, activated leukocytes and activated platelets. A
      significant correlation was found between total levels of MPs, those from
      platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index.
      MPs from CD, but not from HS, impaired endothelium-dependent relaxation in mice
      aorta and flow-induced dilation in mice small mesenteric arteries, MPs from
      inactive CD patients being more effective than those from active patients. CDMPs
      induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide
      (NO)-synthase inhibitor, and was associated with a subtle alteration of the
      balance between NO, reactive oxygen species and the release of COX metabolites.
      CONCLUSIONS: We provide evidence that MPs from CD patients significantly alter
      endothelial and vascular function and therefore, may play a role in CD
      pathophysiology, at least by contributing to uncontrolled vascular-dependent
      intestinal damage.

PMID- 24019900
TI  - The reduced plastid-encoded polymerase-dependent plastid gene expression leads to
      the delayed greening of the Arabidopsis fln2 mutant.
AB  - In Arabidopsis leaf coloration mutants, the delayed greening phenomenon is
      common. Nonetheless, the mechanism remains largely elusive. Here, a delayed
      greening mutant fln2-4 of FLN2 (Fructokinase-Like Protein2) was studied. FLN2 is
      one component of Transcriptionally Active Chromosome (TAC) complex which is
      thought to contain the complete plastid-encoded polymerase (PEP). fln2-4
      displayed albino phenotype on medium without sucrose. The PEP-dependent plastid
      gene expression and chloroplast development were inhibited in fln2-4. Besides
      interacting with thioredoxin z (TRX z), we identified that FLN2 interacted with
      another two members of TAC complex in yeast including its homologous protein FLN1
      (Fructokinase-Like Protein1) and pTAC5. This indicates that FLN2 functions in
      regulation of PEP activity associated with these TAC components. fln2-4 exhibited
      delayed greening on sucrose-containing medium. Comparison of the PEP-dependent
      gene expression among two complete albino mutants (trx z and ptac14), two yellow
      mutants (ecb2-2 and ys1) and the fln2-4 showed that fln2-4 remains partial PEP
      activity. FLN2 and FLN1 are the target proteins of TRX z involved in affecting
      the PEP activity. Together with the data that FLN1 could interact with itself in
      yeast, FLN1 may form a homodimer to replace FLN1-FLN2 as the TRX z target in
      redox pathway for maintaining partial PEP activity in fln2-4. We proposed the
      partial PEP activity in the fln2 mutant allowed plastids to develop into fully
      functional chloroplasts when exogenous sucrose was supplied, and finally the
      mutants exhibited green phenotype. 

PMID- 24019898
TI  - Endoplasmic reticulum (ER) stress inducible factor cysteine-rich with EGF-like
      domains 2 (Creld2) is an important mediator of BMP9-regulated osteogenic
      differentiation of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitors that can undergo
      osteogenic differentiation under proper stimuli. We demonstrated that BMP9 is one
      of the most osteogenic BMPs. However, the molecular mechanism underlying BMP9
      initiated osteogenic signaling in MSCs remains unclear. Through gene expression
      profiling analysis we identified several candidate mediators of BMP9 osteogenic
      signaling. Here, we focus on one such signaling mediator and investigate the
      functional role of cysteine-rich with EGF-like domains 2 (Creld2) in BMP9
      initiated osteogenic signaling. Creld2 was originally identified as an ER stress
      inducible factor localized in the ER-Golgi apparatus. Our genomewide expression
      profiling analysis indicates that Creld2 is among the top up-regulated genes in
      BMP9-stimulated MSCs. We confirm that Creld2 is up-regulated by BMP9 in MSCs.
      ChIP analysis indicates that Smad1/5/8 directly binds to the Creld2 promoter in a
      BMP9-dependent fashion. Exogenous expression of Creld2 in MSCs potentiates BMP9
      induced early and late osteogenic markers, and matrix mineralization. Conversely,
      silencing Creld2 expression inhibits BMP9-induced osteogenic differentiation. In
      vivo stem cell implantation assay reveals that exogenous Creld2 promotes BMP9
      induced ectopic bone formation and matrix mineralization, whereas silencing
      Creld2 expression diminishes BMP9-induced bone formation and matrix
      mineralization. We further show that Creld2 is localized in ER and the ER stress
      inducers potentiate BMP9-induced osteogenic differentiation. Our results strongly
      suggest that Creld2 may be directly regulated by BMP9 and ER stress response may
      play an important role in regulating osteogenic differentiation. 

PMID- 24019902
TI  - Spatial ecology of the critically endangered Fijian crested iguana, Brachylophus
      vitiensis, in an extremely dense population: implications for conservation.
AB  - The Critically Endangered Fijian crested iguana, Brachylophus vitiensis, occurs
      at extreme density at only one location, with estimates of >10,000 iguanas living
      on the 70 hectare island of Yadua Taba in Fiji. We conducted a mark and recapture
      study over two wet seasons, investigating the spatial ecology and intraspecific
      interactions of the strictly arboreal Fijian crested iguana. This species
      exhibits moderate male-biased sexual size dimorphism, which has been linked in
      other lizard species to territoriality, aggression and larger male home ranges.
      We found that male Fijian crested iguanas exhibit high injury levels, indicative
      of frequent aggressive interactions. We did not find support for larger home
      range size in adult males relative to adult females, however male and female
      residents were larger than roaming individuals. Males with established home
      ranges also had larger femoral pores relative to body size than roaming males.
      Home range areas were small in comparison to those of other iguana species, and
      we speculate that the extreme population density impacts considerably on the
      spatial ecology of this population. There was extensive home range overlap within
      and between sexes. Intersexual overlap was greater than intrasexual overlap for
      both sexes, and continuing male-female pairings were observed among residents.
      Our results suggest that the extreme population density necessitates extensive
      home range overlap even though the underlying predictors of territoriality, such
      as male biased sexual size dimorphism and high aggression levels, remain. Our
      findings should be factored in to conservation management efforts for this
      species, particularly in captive breeding and translocation programs. 

PMID- 24019901
TI  - Does a nephron deficit exacerbate the renal and cardiovascular effects of
      obesity?
AB  - It has been hypothesized that a reduced nephron endowment exacerbates the
      hypertensive and renal effects of obesity. We therefore examined the impact of
      diet-induced obesity on renal structure and function, and arterial pressure in a
      genetic model of reduced nephron endowment, the GDNF Heterozygous (HET) mouse. 6
      wk-old male GDNF WT and HET mice were placed on control or high fat (HFF) diet
      for 20 weeks. 24 hr arterial pressure, heart rate and activity (radiotelemetry),
      creatinine clearance and albumin excretion were measured, and kidneys collected
      (histopathology, collagen content). Bodyweights of HFF WT (50.6 +/- 1.2 g) and
      HET (48.8 +/- 1.4 g) mice were ~14 g greater than control mice (37.3 +/- 1.3 g,
      36.4 +/- 1.1 g respectively; Pdiet<0.001). Obesity led to significantly greater
      24 hr MAP (Pdiet<0.001), heart rate (Pdiet<0.01) and lower locomotor activity
      (Pdiet<0.01) in HET and WT mice. Whilst there was no significant impact of
      genotype on 24 hr MAP response to obesity, night-time MAP of obese HET mice was
      significantly greater than obese WT mice (122.3 +/- 1.6 vs 116.9 +/- 1.3 mmHg;
      P<0.05). 24 hr creatinine clearance was 50%, and albumin excretion 180% greater
      in obese WT and HET mice compared to controls (Pdiet<0.05) but this response did
      not differ between genotypes. Obesity induced glomerulomegaly,
      glomerulosclerosis, tubulointerstitial expansion and increased collagen
      accumulation (total, collagen I, V and IV; Pdiet<0.001). Obese GDNF HET mice had
      exacerbated total renal collagen (P<0.01), and greater levels of the collagen I
      subtype compared to kidneys of obese WT mice. In summary, obese nephron-deficient
      GDNF HET mice were able to maintain the high creatinine clearances of obese WT
      mice but at the expense of higher MAP and greater renal fibrosis. Whilst modest,
      our findings support the hypothesis that a reduced nephron endowment increases
      the susceptibility to obesity-induced kidney disease and hypertension.

PMID- 24019903
TI  - Mechanisms of the incretin effect in subjects with normal glucose tolerance and
      patients with type 2 diabetes.
AB  - The incretin effect on insulin secretion was investigated in 8 subjects with type
      2 diabetes (T2D) and 8 with normal glucose tolerance (NGT), using 25, 75, and 125
      g oral glucose tolerance tests (OGTT) and isoglycemic intravenous glucose
      infusions (IIGI). The beta-cell response was evaluated using a model embedding a
      dose-response (slope=glucose sensitivity), an early response (rate sensitivity),
      and potentiation (time-related secretion increase). The incretin effect, as
      OGTT/IIGI ratio, was calculated for each parameter. In NGT, the incretin effect
      on total secretion increased with dose (1.3 +/- 0.1, 1.7 +/- 0.2, 2.2 +/- 0.2
      fold of IIGI, P<0.0001), mediated by a dose-dependent increase of the incretin
      effect on glucose sensitivity (1.9 +/- 0.4, 2.4 +/- 0.4, 3.1 +/- 0.4, P=0.005),
      and a dose-independent enhancement of the incretin effect on rate sensitivity
      (894 [1145], 454 [516], 783 [1259] pmol m(-2) L mmol(-1) above IIGI; median
      [interquartile range], P<0.0001). The incretin effect on potentiation also
      increased (0.97 +/- 0.06, 1.45 +/- 0.20, 1.24 +/- 0.16, P<0.0001). In T2D, the
      incretin effect on total secretion (1.0 +/- 0.1, 1.1 +/- 0.1, 1.3 +/- 0.1,
      P=0.004) and glucose sensitivity (1.2 +/- 0.2, 1.3 +/- 0.2, 2.0 +/- 0.2, P=0.005)
      were impaired vs NGT; however, the incretin effect on rate sensitivity increased
      already at 25 g (269 [169], 284 [301], 193 [465] pmol m(-2) L mmol(-1) above
      IIGI; negligible IIGI rate sensitivity in T2D prevented the calculation of the
      fold increment). OGTT did not stimulate potentiation above IIGI (0.94 +/- 0.04,
      0.89 +/- 0.06, 1.06 +/- 0.09; P<0.01 vs NGT). In the whole group, the incretin
      effect was inversely associated with total secretion during IIGI, although
      systematically lower in T2D. In conclusion, 1) In NGT, glucose sensitivity and
      potentiation mediate the dose-dependent incretin effect increase; 2) In T2D, the
      incretin effect is blunted vs NGT, but rate sensitivity is enhanced at all loads;
      3) Relatively lower incretin effect in NGT is associated with higher secretion
      during IIGI, suggesting that the reduced incretin effect does not result from
      beta-cell dysfunction.

PMID- 24019904
TI  - Validation of the French version of the World Health Organization quality of life
      HIV instrument.
AB  - PURPOSE: Quality of life is a key element in the follow-up of people living with
      HIV/AIDS. The main purpose of this study was to validate the French version of
      the WHOQOL-HIV instrument by comparing this instrument to a generic
      questionnaire. The second objective was to test the reproducibility of this
      questionnaire. METHOD: The WHOQOL-HIV and SF-36 questionnaires were filled out by
      50 patients on two separate occasions with a time interval of 2 weeks. The
      internal consistency, validity and reliability of the WHOQOL-HIV were evaluated.
      RESULTS: The internal consistency was acceptable for the different domains, with
      Cronbach's alpha ranging from 0.937 to 0.944. The facet-domain correlations were
      all statistically significant (p<0.001). There was a correlation between the
      domains from the WHOQOL-HIV and SF-36 questionnaires, with coefficients ranging
      from 0.349 to 0.763 (p<0.05 for all), except for the Spirituality domain. The
      test-retest reliability was suitable for all domains and facets, with
      statistically significant intra-class coefficients between 0.615 and 0.931.
      CONCLUSION: This study demonstrated that the French translation of the WHOQOL-HIV
      instrument is a valid and reproducible tool for the evaluation of the quality of
      life for HIV-infected patients.

PMID- 24019905
TI  - Exploring the functional brain network of Alzheimer's disease: based on the
      computational experiment.
AB  - The purpose of this study is to explore the changes in functional brain networks
      of AD patients using complex network theory. In this study, resting-state fMRI
      datasets of 10 AD patients and 11 healthy controls were collected. Time series of
      90 brain regions were extracted from the fMRI datasets after preprocessing.
      Pearson correlation method was used to calculate the correlation coefficient
      between any two time series. Then, a wide threshold range was selected to
      transform the adjacency matrix to a binary matrix under a different threshold.
      The topology parameters of each binary network were calculated, and all of them
      were then averaged within a group. During the evolution, node betweenness and the
      Euclidean distance between the nodes were set as control factors. Each binary
      network of healthy controls underwent evolution of 100 steps in accordance with
      the evolution rules. Then, the topology parameters of the evolution network were
      calculated. Finally, support vector machine (SVM) was used to classify the
      network topology parameters of the evolution network and to determine whether
      evolution results matched the datasets from AD patients. We found there were
      differing degrees of decline in global efficiency, clustering coefficient, number
      of edges and transitivity in AD patients compared with healthy controls. The
      topology parameters of the evolution network tended toward those of the AD group.
      The results of SVM classification of the evolution network show that the
      evolution network had a greater probability to be classified as an AD patients
      group. A new biological marker for diagnosis of AD was provided through
      comparison of topology parameters between AD patients and healthy controls. The
      study of network evolution strategies enriched the method of brain network
      evolution. The use of SVM to classify the results of network evolution provides
      an objective criteria for determining evolution results. 

PMID- 24019906
TI  - The CD44(high) tumorigenic subsets in lung cancer biospecimens are enriched for
      low miR-34a expression.
AB  - Cellular heterogeneity is an integral part of cancer development and progression.
      Progression can be associated with emergence of cells that exhibit high
      phenotypic plasticity (including "de-differentiation" to primitive developmental
      states), and aggressive behavioral properties (including high tumorigenic
      potentials). We observed that many biomarkers that are used to identify Cancer
      Stem Cells (CSC) can label cell subsets in an advanced clinical stage of lung
      cancer (malignant pleural effusions, or MPE). Thus, CSC-biomarkers may be useful
      for live sorting functionally distinct cell subsets from individual tumors, which
      may enable investigators to hone in on the molecular basis for functional
      heterogeneity. We demonstrate that the CD44(hi) (CD44-high) cancer cell subsets
      display higher clonal, colony forming potential than CD44(lo) cells (n=3) and are
      also tumorigenic (n=2/2) when transplanted in mouse xenograft model. The CD44(hi)
      subsets express different levels of embryonal (de-differentiation) markers or
      chromatin regulators. In archived lung cancer tissues, ALDH markers co-localize
      more with CD44 in squamous cell carcinoma (n=5/7) than Adeno Carcinoma (n=1/12).
      MPE cancer cells and a lung cancer cell line (NCI-H-2122) exhibit chromosomal
      abnormalities and 1p36 deletion (n=3/3). Since miR-34a maps to the 1p36 deletion
      site, low miR-34a expression levels were detected in these cells. The colony
      forming efficiency of CD44(hi) cells, characteristic property of CSC, can be
      inhibited by mir-34a replacement in these samples. In addition the highly
      tumorigenic CD44(hi) cells are enriched for cells in the G2 phase of cell cycle.

PMID- 24019907
TI  - Development of a computerized adaptive test for Schizotypy assessment.
AB  - BACKGROUND: Schizotypal traits in adolescents from the general population
      represent the behavioral expression of liability for psychotic disorders.
      Schizotypy assessment in this sector of population has advanced considerably in
      the last few years; however, it is necessary to incorporate recent advances in
      psychological and educational measurement. OBJECTIVE: The main goal of this study
      was to develop a Computerized Adaptive Test (CAT) to evaluate schizotypy through
      "The Oviedo Questionnaire for Schizotypy Assessment" (ESQUIZO-Q), in non-clinical
      adolescents. METHODS: The final sample consisted of 3,056 participants, 1,469
      males, with a mean age of 15.9 years (SD=1.2). RESULTS: The results indicated
      that the ESQUIZO-Q scores presented adequate psychometric properties under both
      Classical Test Theory and Item Response Theory. The Information Function
      estimated using the Gradual Response Model indicated that the item pool
      effectively assesses schizotypy at the high end of the latent trait. The
      correlation between the CAT total scores and the paper-and-pencil test was 0.92.
      The mean number of presented items in the CAT with the standard error fixed at <=
      0.30 was of 34 items. CONCLUSION: The CAT showed adequate psychometric properties
      for schizotypy assessment in the general adolescent population. The ESQUIZO-Q
      adaptive version could be used as a screening method for the detection of
      adolescents at risk for psychosis in both educational and mental health settings.

PMID- 24019908
TI  - Injury Profile SIMulator, a qualitative aggregative modelling framework to
      predict crop injury profile as a function of cropping practices, and the abiotic
      and biotic environment. I. Conceptual bases.
AB  - The limitation of damage caused by pests (plant pathogens, weeds, and animal
      pests) in any agricultural crop requires integrated management strategies.
      Although significant efforts have been made to i) develop, and to a lesser extent
      ii) combine genetic, biological, cultural, physical and chemical control methods
      in Integrated Pest Management (IPM) strategies (vertical integration), there is a
      need for tools to help manage Injury Profiles (horizontal integration). Farmers
      design cropping systems according to their goals, knowledge, cognition and
      perception of socio-economic and technological drivers as well as their physical,
      biological, and chemical environment. In return, a given cropping system, in a
      given production situation will exhibit a unique injury profile, defined as a
      dynamic vector of the main injuries affecting the crop. This simple description
      of agroecosystems has been used to develop IPSIM (Injury Profile SIMulator), a
      modelling framework to predict injury profiles as a function of cropping
      practices, abiotic and biotic environment. Due to the tremendous complexity of
      agroecosystems, a simple holistic aggregative approach was chosen instead of
      attempting to couple detailed models. This paper describes the conceptual bases
      of IPSIM, an aggregative hierarchical framework and a method to help specify
      IPSIM for a given crop. A companion paper presents a proof of concept of the
      proposed approach for a single disease of a major crop (eyespot on wheat). In the
      future, IPSIM could be used as a tool to help design ex-ante IPM strategies at
      the field scale if coupled with a damage sub-model, and a multicriteria sub-model
      that assesses the social, environmental, and economic performances of simulated
      agroecosystems. In addition, IPSIM could also be used to help make diagnoses on
      commercial fields. It is important to point out that the presented concepts are
      not crop- or pest-specific and that IPSIM can be used on any crop. 

PMID- 24019909
TI  - Efficient repopulation of genetically derived rho zero cells with exogenous
      mitochondria.
AB  - Mitochondria are involved in a variety of cellular biochemical pathways among
      which the ATP production by oxidative phosphorylation (OXPHOS) represents the
      most important function of the organelle. Since mitochondria contain their own
      genome encoding subunits of the OXPHOS apparatus, mtDNA mutations can cause
      different mitochondrial diseases. The impact of these mutations can be
      characterized by the trans-mitochondrial cybrid technique based on mtDNA-depleted
      cells (rho(0)) as acceptors of exogenous mitochondria. The aim of the present
      work was to compare rho(0) cells obtained by long term ethidium bromide treatment
      and by a mitochondrial targeted restriction endonuclease, respectively, as
      mitochondrial acceptors for trans-mitochondrial cybrid generation. Fusion cells
      have mitochondrial respiratory functions comparable to their parental wild type
      cells, regardless the strategy utilized to obtain the rho(0) acceptor cells.
      Therefore, the newly developed enzymatic strategy for mtDNA depletion is a more
      convenient and suitable tool for a broader range of applications. 

PMID- 24019910
TI  - Reduced cortical thickness in primary open-angle glaucoma and its relationship to
      the retinal nerve fiber layer thickness.
AB  - OBJECTIVES: To examine possible changes in cortical thickness and their
      relationship to retinal nerve fiber layer (RNFL) thickness in patients with
      primary open-angle glaucoma (POAG). MATERIALS AND METHODS: Thirty-six patients
      with POAG and 40 matched healthy controls were enrolled in this study. All
      subjects underwent a comprehensive ophthalmologic examination and a high
      resolution structural magnetic resonance scan. Cortical thickness analysis was
      used to assess the changes between patients and controls. Correlations between
      the thickness of the visual cortex and RNFL thickness were also analyzed.
      Finally, the relationship between the severity of changes in the visual cortex
      and RNFL thickness was evaluated by comparing patients with mild and severe
      groups. RESULTS: POAG patients showed significant bilateral cortical thinning in
      the anterior half of the visual cortex around the calcarine sulci (left BA 17 and
      BA 18, right BA17) and in some smaller regions located in the left middle
      temporal gyrus (BA37) and fusiform gyrus (BA19). The thickness of the visual
      cortex correlated positively with RNFL thickness (left, r = 0.44, p = 0.01;
      right, r = 0.38, p = 0.03). Significant differences between mild and severe
      groups were observed with regard to both RNFL thickness and the thickness of
      bilateral visual cortex (p < 0.05). CONCLUSION: Our findings indicate that
      cortical thickness analysis may be sufficiently sensitive to detect cortical
      alterations in POAG and that the measurement has great potential for clinical
      application.

PMID- 24019911
TI  - Who is who? Interpretation of multiple occurrences of the Chinese reflexive:
      evidence from real-time sentence processing.
AB  - Theoretical linguists claim that the notorious reflexive ziji 'self' in Mandarin
      Chinese, if occurring more than once in a single sentence, can take distinct
      antecedents. This study tackles possibly the most interesting puzzle in the
      linguistic literature, investigating how two occurrences of ziji in a single
      sentence are interpreted and whether or not there are mixed readings, i.e., these
      zijis are interpretively bound by distinct antecedents. Using 15 Chinese
      sentences each having two zijis, we conducted two sentence reading experiments
      based on a modified self-paced reading paradigm. The general interpretation
      patterns observed showed that the majority of participants associated both zijis
      with the same local antecedent, which was consistent with Principle A of the
      Standard Binding Theory and previous experimental findings involving a single
      ziji. In addition, mixed readings also occurred, but did not pattern as claimed
      in the theoretical linguistic literature (i.e., one ziji is bound by a long
      distance antecedent and the other by a local antecedent). Based on these results,
      we argue that: (i) mixed readings were due to manifold, interlocking and
      conflicting perspectives taken by the participants; and (ii) cases of multiple
      occurrences of ziji taking distinct antecedents are illicit in Chinese syntax,
      since the speaker, when expressing a sentence, can select only one P(erspective)
      Center that referentially denotes the psychological perspective in which the
      sentence is situated. 

PMID- 24019912
TI  - Characterisation of nuclear architectural alterations during in vitro
      differentiation of human stem cells of myogenic origin.
AB  - Cell differentiation is based on a synchronised orchestra of complex pathways of
      intrinsic and extrinsic signals that manifest in the induced expression of
      specific transcription factors and pivotal genes within the nucleus. One cannot
      ignore the epigenetic status of differentiating cells, comprising not only
      histones and DNA modifications but also the spatial and temporal intranuclear
      chromatin organisation, which is an important regulator of nuclear processes. In
      the present study, we investigated the nuclear architecture of human primary
      myoblasts and myocytes in an in vitro culture, with reference to global changes
      in genomic expression. Repositioning of the chromosomal centromeres, along with
      alterations in the nuclear shape and volume, was observed as a consequence of
      myotube formation. Moreover, the microarray data showed that during in vitro
      myogenesis cells tend to silence rather than induce gene expression. The creation
      of a chromosome map marked with gene expression changes that were at least 2-fold
      confirmed the observation. Additionally, almost all of the chromosomal
      centromeres in the differentiated cells preferentially localised near the nuclear
      periphery when compared to the undifferentiated cells. The exceptions were
      chromosomes 7 and 11, in which we were unable to confirm the centromere
      repositioning. In our opinion, this is the first reported observation of the
      movement of chromosomal centromeres along differentiating myogenic cells. Based
      on these data we can conclude that the myogenic differentiation with global gene
      expression changes is accompanied by the spatial repositioning of chromosomes and
      chromatin remodelling, which are important processes that regulate cell
      differentiation. 

PMID- 24019913
TI  - Tractography of the corpus callosum in Huntington's disease.
AB  - White matter abnormalities have been shown in presymptomatic and symptomatic
      Huntington's disease (HD) subjects using Magnetic Resonance Imaging (MRI) and
      Diffusion Tensor Imaging (DTI) methods. The largest white matter tract, the
      corpus callosum (CC), has been shown to be particularly vulnerable; however,
      little work has been done to investigate the regional specificity of tract
      abnormalities in the CC. Thus, this study examined the major callosal tracts by
      applying DTI-based tractography. Using TrackVis, a previously defined region of
      interest tractography method parcellating CC into seven major tracts based on
      target region was applied to 30 direction DTI data collected from 100 subjects:
      presymptomatic HD (Pre-HD) subjects (n=25), HD patients (n=25) and healthy
      control subjects (n=50). Tractography results showed decreased fractional
      anisotropy (FA) and increased radial diffusivity (RD) across broad regions of the
      CC in Pre-HD subjects. Similar though more severe deficits were seen in HD
      patients. In Pre-HD and HD, callosal FA and RD were correlated with Disease
      Burden/CAG repeat length as well as motor (UHDRSI) and cognitive (URDRS2)
      assessments. These results add evidence that CC pathways are compromised prior to
      disease onset with possible demyelination occurring early in the disease and
      suggest that CAG repeat length is a contributing factor to connectivity deficits.
      Furthermore, disruption of these callosal pathways potentially contributes to the
      disturbances of motor and cognitive processing that characterize HD.

PMID- 24019914
TI  - Therapeutic effects of anti-CD115 monoclonal antibody in mouse cancer models
      through dual inhibition of tumor-associated macrophages and osteoclasts.
AB  - Tumor progression is promoted by Tumor-Associated Macrophages (TAMs) and
      metastasis-induced bone destruction by osteoclasts. Both myeloid cell types
      depend on the CD115-CSF-1 pathway for their differentiation and function. We used
      3 different mouse cancer models to study the effects of targeting cancer host
      myeloid cells with a monoclonal antibody (mAb) capable of blocking CSF-1 binding
      to murine CD115. In mice bearing sub-cutaneous EL4 tumors, which are CD115
      negative, the anti-CD115 mAb depleted F4/80(+) CD163(+) M2-type TAMs and reduced
      tumor growth, resulting in prolonged survival. In the MMTV-PyMT mouse model, the
      spontaneous appearance of palpable mammary tumors was delayed when the anti-CD115
      mAb was administered before malignant transition and tumors became palpable only
      after termination of the immunotherapy. When administered to mice already bearing
      established PyMT tumors, anti-CD115 treatment prolonged their survival and
      potentiated the effect of chemotherapy with Paclitaxel. As shown by
      immunohistochemistry, this therapeutic effect correlated with the depletion of
      F4/80(+)CD163(+) M2-polarized TAMs. In a breast cancer model of bone metastasis,
      the anti-CD115 mAb potently blocked the differentiation of osteoclasts and their
      bone destruction activity. This resulted in the inhibition of cancer-induced
      weight loss. CD115 thus represents a promising target for cancer immunotherapy,
      since a specific blocking antibody may not only inhibit the growth of a primary
      tumor through TAM depletion, but also metastasis-induced bone destruction through
      osteoclast inhibition. 

PMID- 24019915
TI  - Comparative transcriptome profiling of an SV40-transformed human fibroblast
      (MRC5CVI) and its untransformed counterpart (MRC-5) in response to UVB
      irradiation.
AB  - Simian virus 40 (SV40) transforms cells through the suppression of tumor
      suppressive responses by large T and small t antigens; studies on the effects of
      these two oncoproteins have greatly improved our knowledge of tumorigenesis.
      Large T antigen promotes cellular transformation by binding and inactivating p53
      and pRb tumor suppressor proteins. Previous studies have shown that not all of
      the tumor-suppressive responses were inactivated in SV40-transformed cells;
      however, the underlying cause is not fully studied. In this study, we
      investigated the UVB-responsive transcriptome of an SV40-transformed fibroblast
      (MRC5CVI) and that of its untransformed counterpart (MRC-5). We found that, in
      response to UVB irradiation, MRC-5 and MRC5CVI commonly up-regulated the
      expression of oxidative phosphorylation genes. MRC-5 up-regulated the expressions
      of chromosome condensation, DNA repair, cell cycle arrest, and apoptotic genes,
      but MRC5CVI did not. Further cell death assays indicated that MRC5CVI was more
      sensitive than MRC-5 to UVB-induced cell death with increased caspase-3
      activation; combining with the transcriptomic results suggested that MRC5CVI may
      undergo UVB-induced cell death through mechanisms other than transcriptional
      regulation. Our study provides a further understanding of the effects of SV40
      transformation on cellular stress responses, and emphasizes the value of SV40
      transformed cells in the researches of sensitizing neoplastic cells to
      radiations. 

PMID- 24019916
TI  - Wheat seedling emergence from deep planting depths and its relationship with
      coleoptile length.
AB  - Successful stand establishment is prerequisite for optimum crop yields. In some
      low-precipitation zones, wheat (Triticum aestivum L.) is planted as deep as 200
      mm below the soil surface to reach adequate soil moisture for germination. To
      better understand the relationship of coleoptile length and other seed
      characteristics with emergence from deep planting (EDP), we evaluated 662 wheat
      cultivars grown around the world since the beginning of the 20(th) century.
      Coleoptile length of collection entries ranged from 34 to 114 mm. A specialized
      field EDP test showed dramatic emergence differences among cultivars ranging from
      0-66% by 21 days after planting (DAP). Less than 1% of entries had any seedlings
      emerged by 7 DAP and 43% on day 8. A wide range of EDP within each coleoptile
      length class suggests the involvement of genes other than those controlling
      coleoptile length. Emergence was correlated with coleoptile length, but some
      lines with short coleoptiles ranked among the top emergers. Coleoptiles longer
      than 90 mm showed no advantage for EDP and may even have a negative effect.
      Overall, coleoptile length accounted for only 28% of the variability in emergence
      among entries; much lower than the 60% or greater reported in previous studies.
      Seed weight had little correlation with EDP. Results show that EDP is largely
      controlled by yet poorly understood mechanisms other than coleoptile length. 

PMID- 24019917
TI  - Relationships between cell cycle regulator gene copy numbers and protein
      expression levels in Schizosaccharomyces pombe.
AB  - We previously determined the copy number limits of overexpression for cell
      division cycle (cdc) regulatory genes in the fission yeast Schizosaccharomyces
      pombe using the "genetic tug-of-war" (gTOW) method. In this study, we measured
      the levels of tandem affinity purification (TAP)-tagged target proteins when
      their copy numbers are increased in gTOW. Twenty analyzed genes showed roughly
      linear correlations between increased protein levels and gene copy numbers, which
      suggested a general lack of compensation for gene dosage in S. pombe. Cdc16 and
      Sid2 protein levels but not their mRNA levels were much lower than that expected
      by their copy numbers, which suggested the existence of a post-transcriptional
      down regulation of these genes. The cyclin Cig1 protein level and its mRNA level
      were much higher than that expected by its copy numbers, which suggested a
      positive feedback mechanism for its expression. A higher Cdc10 protein level and
      its mRNA level, probably due to cloning its gene into a plasmid, indicated that
      Cdc10 regulation was more robust than that previously predicted. 

PMID- 24019918
TI  - Voltage dependence of proton pumping by bacteriorhodopsin mutants with altered
      lifetime of the M intermediate.
AB  - The light-driven proton pump bacteriorhodopsin (BR) from Halobacterium salinarum
      is tightly regulated by the [H(+)] gradient and transmembrane potential. BR
      exhibits optoelectric properties, since spectral changes during the photocycle
      are kinetically controlled by voltage, which predestines BR for optical storage
      or processing devices. BR mutants with prolonged lifetime of the blue-shifted M
      intermediate would be advantageous, but the optoelectric properties of such
      mutants are still elusive. Using expression in Xenopus oocytes and two-electrode
      voltage-clamping, we analyzed photocurrents of BR mutants with kinetically
      destabilized (F171C, F219L) or stabilized (D96N, D96G) M intermediate in response
      to green light (to probe H(+) pumping) and blue laser flashes (to probe
      accumulation/decay of M). These mutants have divergent M lifetimes. As for BR-WT,
      this strictly correlates with the voltage dependence of H(+) pumping. BR-F171C
      and BR-F219L showed photocurrents similar to BR-WT. Yet, BR-F171C showed a weaker
      voltage dependence of proton pumping. For both mutants, blue laser flashes
      applied during and after green-light illumination showed reduced M accumulation
      and shorter M lifetime. In contrast, BR-D96G and BR-D96N exhibited small
      photocurrents, with nonlinear current-voltage curves, which increased strongly in
      the presence of azide. Blue laser flashes showed heavy M accumulation and
      prolonged M lifetime, which accounts for the strongly reduced H(+) pumping rate.
      Hyperpolarizing potentials augmented these effects. The combination of M
      stabilizing and -destabilizing mutations in BR-D96G/F171C/F219L (BR-tri) shows
      that disruption of the primary proton donor Asp-96 is fatal for BR as a proton
      pump. Mechanistically, M destabilizing mutations cannot compensate for the
      disruption of Asp-96. Accordingly, BR-tri and BR-D96G photocurrents were similar.
      However, BR-tri showed negative blue laser flash-induced currents even without
      actinic green light, indicating that Schiff base deprotonation in BR-tri exists
      in the dark, in line with previous spectroscopic investigations. Thus, M
      stabilizing mutations, including the triple mutation, drastically interfere with
      electrochemical H(+) gradient generation. 

PMID- 24019919
TI  - Xanthomonas oryzae pv. oryzae type III effector XopN targets OsVOZ2 and a
      putative thiamine synthase as a virulence factor in rice.
AB  - Xanthomonasoryzae pv. oryzae (Xoo) is spread systemically through the xylem
      tissue and causes bacterial blight in rice. We evaluated the roles of Xanthomonas
      outer proteins (Xop) in the Xoo strain KXO85 in a Japonica-type rice cultivar,
      Dongjin. Five xop gene knockout mutants (xopQ KXO85 , xopX KXO85 , xopP1 KXO85 ,
      xopP2 KXO85 , and xopN KXO85 ) were generated by EZ-Tn5 mutagenesis, and their
      virulence was assessed in 3-month-old rice leaves. Among these mutants, the xopN
      KXO85 mutant appeared to be less virulent than the wild-type KXO85; however, the
      difference was not statistically significant. In contrast, the xopN KXO85 mutant
      exhibited significantly less virulence in flag leaves after flowering than the
      wild-type KXO85. These observations indicate that the roles of Xop in Xoo
      virulence are dependent on leaf stage. We chose the xopN gene for further
      characterization because the xopN KXO85 mutant showed the greatest influence on
      virulence. We confirmed that XopNKXO85 is translocated into rice cells, and its
      gene expression is positively regulated by HrpX. Two rice proteins, OsVOZ2 and a
      putative thiamine synthase (OsXNP), were identified as targets of XopNKXO85 by
      yeast two-hybrid screening. Interactions between XopNKXO85 and OsVOZ2 and OsXNP
      were further confirmed in planta by bimolecular fluorescence complementation and
      in vivo pull-down assays. To investigate the roles of OsVOZ2 in interactions
      between rice and Xoo, we evaluated the virulence of the wild-type KXO85 and xopN
      KXO85 mutant in the OsVOZ2 mutant line PFG_3A-07565 of Dongjin. The wild-type
      KXO85 and xopN KXO85 mutant were significantly less virulent in the mutant rice
      line. These results indicate that XopNKXO85 and OsVOZ2 play important roles both
      individually and together for Xoo virulence in rice. 

PMID- 24019920
TI  - Fusogenic-oligoarginine peptide-mediated delivery of siRNAs targeting the CIP2A
      oncogene into oral cancer cells.
AB  - Despite a better understanding of the pathogenesis of oral cancer, its treatment
      outcome remains poor. Thus, there is a need for new therapeutic strategies to
      improve the prognosis of this disease. RNA interference (RNAi) appears to be a
      promising therapeutic tool for the treatment of many diseases, including oral
      cancer. However, an obstacle for RNAi-mediated therapies has been delivery, in
      particular, the retention of small interfering RNAs (siRNAs) in endosomes and
      their subsequent degradation in lysosomes, resulting in inefficient gene
      silencing. Thus, the current study examined the feasibility of designing and
      utilizing a peptide, termed 599, consisting of a synthetic influenza virus
      derived endosome-disruptive fusogenic peptide sequence and a stretch of cationic
      cell-penetrating nona(D-arginine) residues, to deliver siRNAs into oral cancer
      cells and induce silencing of the therapeutic target, CIP2A, an oncoprotein
      overexpressed in various human malignancies including oral cancer. Increasing the
      599 peptide-to-siRNA molar ratio demonstrated a higher binding capacity for siRNA
      molecules and enhanced siRNA delivery into the cytoplasm of oral cancer cells. In
      fact, quantitative measurements of siRNA delivery into cells demonstrated that a
      50?1 peptide-to-siRNA molar ratio could deliver 18-fold higher amounts of siRNAs
      compared to cells treated with siRNA alone with no significant long-term
      cytotoxic effects. Most importantly, the 599 peptide-mediated siRNA delivery
      promoted significant CIP2A mRNA and protein silencing which resulted in decreased
      oral cancer cell invasiveness and anchorage-independent growth. Together, these
      data demonstrate that a chimeric peptide consisting of a fusogenic sequence, in
      combination with cell-penetrating residues, can be used to effectively deliver
      siRNAs into oral cancer cells and induce the silencing of its target gene,
      potentially offering a new therapeutic strategy in combating oral cancer. 

PMID- 24019921
TI  - Word frequency and the attentional blink: the effects of target difficulty on
      retrieval and consolidation processes.
AB  - BACKGROUND: When a second target (T2) is presented in close succession of a first
      target (T1) within a stream of non-targets, people often fail to detect T2-a
      deficit known as the attentional blink (AB). Two types of theories can be
      distinguished that have tried to account for this phenomenon. Whereas attentional
      control theories suggest that protection of consolidation processes induces the
      AB, limited-resource theories claim that the AB is caused by a lack of resources.
      According to the latter type of theories, increasing difficulty of one or both
      targets should increase the magnitude of the AB. Similarly, attentional-control
      theories predict that a difficult T1 increases the AB due to prolonged
      processing. However, the prediction for T2 is not as straightforward. Prolonged
      processing of T2 could cause conflicts and increase the AB. However, if
      consolidation of T2 is postponed without loss of identity, the AB might be
      attenuated. METHODOLOGY/PRINCIPAL FINDINGS: Participants performed an AB task
      that consisted of a stream of distractor non-words and two target words.
      Difficulty of T1 and T2 was manipulated by varying word-frequency. Overall
      performance for high-frequency words was better than for low-frequency words.
      When T1 was highly frequent, the AB was reduced. The opposite effect was found
      for T2. When T2 was highly frequent, performance during the AB period was
      relatively worse than for a low-frequency T2. A threaded-cognition model of the
      AB was presented that simulated the observed pattern of behavior by taking
      changes in the time-course of retrieval and consolidation processes into account.
      Our results were replicated in a subsequent ERP study. CONCLUSIONS/SIGNIFICANCE:
      The finding that a difficult low-frequency T2 reduces the magnitude of the AB is
      at odds with limited-resource accounts of the AB. However, it was successfully
      accounted for by the threaded-cognition model, thus providing an explanation in
      terms of attentional control.

PMID- 24019922
TI  - Isolation, identification and characterization of an electrogenic microalgae
      strain.
AB  - Extracellular electron transfer involving microbes is important as it closely
      reflects the ability of cells to communicate with the environment. However, there
      are few reports on electron transfer mechanisms of pure microalgae and a lack of
      any model alga to study the transfer processes. In the present study, nine green
      microalgae species were isolated from wastewater and characterized in terms of
      their ability to transfer electrons between cells and an electrode. One species
      showed direct electron transfer via membrane-associated proteins and indirect
      electron transfer via secreted oxygen. The microalga was identified as
      Desmodesmus sp. based on phylogenetic analysis and electron microscopy.
      Electrochemical tests demonstrated that Desmodesmus sp. was able to act as a
      cathodic microorganism. Stable current densities of -0.24, 35.54 and 170 mA m(-2)
      were achieved at potentials of +0.2, -0.2 and -0.4 V, respectively, under
      illumination. Dissolved oxygen concentration measurement showed gradients within
      the microalgae biofilm: 18.3 mg L(-1) in light decreasing to 4.29 mg L(-1) in the
      dark. This study diversified the exoelectrogen library and provided a potential
      model microalga to explore the associated mechanism of extracellular electron
      transfer. 

PMID- 24019923
TI  - Greenhouse gas flux and crop productivity after 10 years of reduced and no
      tillage in a wheat-maize cropping system.
AB  - Appropriate tillage plays an important role in mitigating the emissions of
      greenhouse gases (GHG) in regions with higher crop yields, but the emission
      situations of some reduced tillage systems such as subsoiling, harrow tillage and
      rotary tillage are not comprehensively studied. The objective of this study was
      to evaluate the emission characteristics of GHG (CH4 and N2O) under four reduced
      tillage systems from October 2007 to August 2009 based on a 10-yr tillage
      experiment in the North China Plain, which included no-tillage (NT) and three
      reduced tillage systems of subsoil tillage (ST), harrow tillage (HT) and rotary
      tillage (RT), with the conventional tillage (CT) as the control. The soil under
      the five tillage systems was an absorption sink for CH4 and an emission source
      for N2O. The soil temperature positive impacted on the CH4 absorption by the
      soils of different tillage systems, while a significant negative correlation was
      observed between the absorption and soil moisture. The main driving factor for
      increased N2O emission was not the soil temperature but the soil moisture and the
      content of nitrate. In the two rotation cycle of wheat-maize system (10/2007
      10/2008 and 10/2008-10/2009), averaged cumulative uptake fluxes of CH4 under CT,
      ST, HT, RT and NT systems were approximately 1.67, 1.72, 1.63, 1.77 and 1.17 t
      ha(-1) year(-1), respectively, and meanwhile, approximately 4.43, 4.38, 4.47,
      4.30 and 4.61 t ha(-1) year(-1) of N2O were emitted from soil of these systems,
      respectively. Moreover, they also gained 33.73, 34.63, 32.62, 34.56 and 27.54 t
      ha(-1) yields during two crop-rotation periods, respectively. Based on these
      comparisons, the rotary tillage and subsoiling mitigated the emissions of CH4 and
      N2O as well as improving crop productivity of a wheat-maize cropping system. 

PMID- 24019925
TI  - Functional display of platelet-binding VWF fragments on filamentous
      bacteriophage.
AB  - von Willebrand factor (VWF) tethers platelets to sites of vascular injury via
      interaction with the platelet surface receptor, GPIb. To further define the VWF
      sequences required for VWF-platelet interaction, a phage library displaying
      random VWF protein fragments was screened against formalin-fixed platelets. After
      3 rounds of affinity selection, DNA sequencing of platelet-bound clones
      identified VWF peptides mapping exclusively to the A1 domain. Aligning these
      sequences defined a minimal, overlapping segment spanning P1254-A1461, which
      encompasses the C1272-C1458 cystine loop. Analysis of phage carrying a mutated A1
      segment (C1272/1458A) confirmed the requirement of the cystine loop for optimal
      binding. Four rounds of affinity maturation of a randomly mutagenized A1 phage
      library identified 10 and 14 unique mutants associated with enhanced platelet
      binding in the presence and absence of botrocetin, respectively, with 2 mutants
      (S1370G and I1372V) common to both conditions. These results demonstrate the
      utility of filamentous phage for studying VWF protein structure-function and
      identify a minimal, contiguous peptide that bind to formalin-fixed platelets,
      confirming the importance of the VWF A1 domain with no evidence for another
      independently platelet-binding segment within VWF. These findings also point to
      key structural elements within the A1 domain that regulate VWF-platelet adhesion.

PMID- 24019924
TI  - A meta analysis and hierarchical classification of HU-based atherosclerotic
      plaque characterization criteria.
AB  - BACKGROUND: Many computed tomography (CT) studies have reported that lipid-rich,
      presumably rupture-prone atherosclerotic plaques can be characterized according
      to their Hounsfield Unit (HU) value. However, the published HU-based
      characterization criteria vary considerably. The present study aims to
      systematically analyze these values and empirically derive a hierarchical
      classification of the HU-based criteria which can be referred in clinical
      situation. MATERIAL AND METHODS: A systematic search in PubMed and Embase for
      publications with HU-criteria to characterize lipid-rich and fibrous
      atherosclerotic plaques resulted in 36 publications, published between 1998 and
      2011. The HU-criteria were systematically analyzed based on the characteristics
      of the reporting study. Significant differences between HU-criteria were checked
      using Student's t-test. Subsequently, a hierarchical classification of HU
      criteria was developed based on the respective study characteristics. RESULTS: No
      correlation was found between HU-criteria and the reported lumen contrast
      enhancement. Significant differences were found for HU-criteria when pooled
      according to the respective study characteristics: examination type, vessel type,
      CT-vendor, detector-rows, voltage-setting, and collimation-width. The
      hierarchical classification resulted in 21 and 22 CT attenuation value
      categories, for lipid-rich and fibrous plaque, respectively. More than 50% of the
      hierarchically classified HU-criteria were significantly different. CONCLUSION:
      In conclusion, variations in the reported CT attenuation values for lipid-rich
      and fibrous plaque are so large that generalized values are unreliable for
      clinical use. The proposed hierarchical classification can be used to determine
      reference CT attenuation values of lipid-rich and fibrous plaques for the local
      setting.

PMID- 24019926
TI  - A combined marker of inflammation in individuals with mania.
AB  - BACKGROUND: Markers of immune activation have been associated with mania but have
      not been examined in combination. We studied the association between mania and an
      inflammation score based on four immune markers. METHODS: A total of 57
      individuals with mania were assessed at up to three time points: the day of
      hospital admission, evaluation several days later, and six-month follow-up. Also
      assessed were 207 non-psychiatric controls and 330 individuals with recent onset
      psychosis, multi-episode schizophrenia, or bipolar disorder depression. A
      combined inflammation score was calculated by factor analysis of the levels of
      class-specific antibodies to the NR peptide of the NMDA receptor; gliadin; Mason
      Pfizer monkey virus protein 24; and Toxoplasma gondii. Inflammation scores among
      groups were compared by multivariate analyses. The inflammation score of the
      mania group at evaluation was studied as a predictor of re-hospitalization in the
      follow-up period. RESULTS: The combined inflammation score of the mania group at
      hospital admission and at evaluation differed significantly from that of the non
      psychiatric controls (t=3.95, 4.10, p<.001). The inflammation score was
      significantly decreased at six month follow-up (F=5.85, p=0.004). There were not
      any significant differences in the inflammation scores of any of the other
      psychiatric groups and that of the controls. Within the mania group, an elevated
      inflammation score at evaluation predicted re-hospitalization (Hazard ratio=7.12,
      p=.005). CONCLUSIONS: Hospitalization for mania is associated with immune
      activation. The level of this activation is predictive of subsequent re
      hospitalization. Interventions for the modulation of inflammation should be
      evaluated for the therapy of individuals with mania.

PMID- 24019927
TI  - The cytoskeletal protein RHAMM and ERK1/2 activity maintain the pluripotency of
      murine embryonic stem cells.
AB  - Receptor for hyaluronan mediated motility (RHAMM, encoded by HMMR) may be a cell
      surface receptor for hyaluronan that regulates embryonic stem cell pluripotency
      and differentiation, however, a precise mechanism for its action is not known. We
      examined murine embryonic stem cells with and without hemizygous genomic mutation
      of Hmmr/RHAMM, but we were not able to find RHAMM on the cell-surface. Rather,
      RHAMM localized to the microtubule cytoskeleton and along mitotic spindles.
      Genomic loss of Hmmr/RHAMM did not alter cell cycle progression but augmented
      differentiation and attenuated pluripotency in murine embryonic stem cells.
      Through a candidate screen of small-molecule kinase inhibitors, we identified
      ERK1/2 and aurora kinase A as barrier kinases whose inhibition was sufficient to
      rescue pluripotency in RHAMM(+/-) murine embryonic stem cells. Thus, RHAMM is not
      found on the cell-surface of embryonic stem cells, but it is required to maintain
      pluripotency and its dominant mechanism of action is through the modulation of
      signal transduction pathways at microtubules. 

PMID- 24019928
TI  - The axe-txe complex of Enterococcus faecium presents a multilayered mode of toxin
      antitoxin gene expression regulation.
AB  - Multidrug-resistant variants of human pathogens from the genus Enterococcus
      represent a significant health threat as leading agents of nosocomial infections.
      The easy acquisition of plasmid-borne genes is intimately involved in the spread
      of antibiotic resistance in enterococci. Toxin-antitoxin (TA) systems play a
      major role in both maintenance of mobile genetic elements that specify antibiotic
      resistance, and in bacterial persistence and virulence. Expression of toxin and
      antitoxin genes must be in balance as inappropriate levels of toxin can be
      dangerous to the host. The controlled production of toxin and antitoxin is
      usually achieved by transcriptional autoregulation of TA operons. One of the most
      prevalent TA modules in enterococcal species is axe-txe which is detected in a
      majority of clinical isolates. Here, we demonstrate that the axe-txe cassette
      presents a complex pattern of gene expression regulation. Axe-Txe cooperatively
      autorepress expression from a major promoter upstream of the cassette. However,
      an internal promoter that drives the production of a newly discovered transcript
      from within axe gene combined with a possible modulation in mRNA stability play
      important roles in the modulation of Axe:Txe ratio to ensure controlled release
      of the toxin. 

PMID- 24019929
TI  - Altered expression of cyclin A 1 in muscle of patients with facioscapulohumeral
      muscle dystrophy (FSHD-1).
AB  - OBJECTIVES: Cyclin A1 regulates cell cycle activity and proliferation in somatic
      and germ-line cells. Its expression increases in G1/S phase and reaches a maximum
      in G2 and M phases. Altered cyclin A1 expression might contribute to clinical
      symptoms in facioscapulohumeral muscular dystrophy (FSHD). METHODS: Muscle
      biopsies were taken from the Vastus lateralis muscle for cDNA microarray, RT-PCR,
      immunohistochemistry and Western blot analyses to assess RNA and protein
      expression of cyclin A1 in human muscle cell lines and muscle tissue. Muscle
      fibers diameter was calculated on cryosections to test for hypertrophy. RESULTS:
      cDNA microarray data showed specifically elevated cyclin A1 levels in FSHD vs.
      other muscular disorders such as caveolinopathy, dysferlinopathy, four and a half
      LIM domains protein 1 deficiency and healthy controls. Data could be confirmed
      with RT-PCR and Western blot analysis showing up-regulated cyclin A1 levels also
      at protein level. We found also clear signs of hypertrophy within the Vastus
      lateralis muscle in FSHD-1 patients. CONCLUSIONS: In most somatic human cell
      lines, cyclin A1 levels are low. Overexpression of cyclin A1 in FSHD indicates
      cell cycle dysregulation in FSHD and might contribute to clinical symptoms of
      this disease.

PMID- 24019930
TI  - Restoration of the normal splicing pattern of the PLP1 gene by means of an
      antisense oligonucleotide directed against an exonic mutation.
AB  - An exonic missense mutation, c.436C>G, in the PLP1 gene of a patient affected by
      the hypomyelinating leukodystrophy, Pelizaeus-Merzbacher disease, has previously
      been found to be responsible for the alteration of the canonical alternative
      splicing profile of the PLP1 gene leading to the loss of the longer PLP isoform.
      Here we show that the presence of the c.436C>G mutation served to introduce
      regulatory motifs that appear to be responsible for the perturbed splicing
      pattern that led to loss of the major PLP transcript. With the aim of disrupting
      the interaction between the PLP1 splicing regulatory motifs and their cognate
      splicing factors, we designed an antisense oligonucleotide-based in vitro
      correction protocol that successfully restored PLP transcript production in
      oligodendrocyte precursor cells. 

PMID- 24019931
TI  - SGO1 maintains bovine meiotic and mitotic centromeric cohesions of sister
      chromatids and directly affects embryo development.
AB  - Shugoshin (SGO) is a critical factor that enforces cohesion from segregation of
      paired sister chromatids during mitosis and meiosis. It has been studied mainly
      in invertebrates. Knowledge of SGO(s) in a mammalian system has only been
      reported in the mouse and Hela cells. In this study, the functions of SGO1 in
      bovine oocytes during meiotic maturation, early embryonic development and somatic
      cell mitosis were investigated. The results showed that SGO1 was expressed from
      germinal vesicle (GV) to the metaphase II stage. SGO1 accumulated on condensed
      and scattered chromosomes from pre-metaphase I to metaphase II. The over
      expression of SGO1 did not interfere with the process of homologous chromosome
      separation, although once separated they were unable to move to the opposing
      spindle poles. This often resulted in the formation of oocytes with 60 replicated
      chromosomes. Depletion of SGO1 in GV oocytes affected chromosomal separation
      resulting in abnormal chromosome alignment at a significantly higher proportion
      than in control oocytes. Knockdown of SGO1 expression significantly decreased the
      embryonic developmental rate and quality. To further confirm the function(s) of
      SGO1 during mitosis, bovine embryonic fibroblast cells were transfected with SGO1
      siRNAs. SGO1 depletion induced the premature dissociation of chromosomal cohesion
      at the centromere and along the chromosome arm giving rise to abnormal appearing
      mitotic patterns. The results of this study infer that SGO1 is involved in the
      centromeric cohesion of sister chromatids and chromosomal movement towards the
      spindle poles. Depletion of SGO1 causes arrestment of cell division in meiosis
      and mitosis. 

PMID- 24019932
TI  - Disturbance of intentionality: a phenomenological study of body-affecting first
      rank symptoms in schizophrenia.
AB  - OBJECTIVES: In 1950, Kurt Schneider proposed that a considerable number of
      schizophrenia patients develop first-rank symptoms (FRS). In such cases, patients
      report made experiences, replaced control of will, thought insertion, broadcast
      or withdrawal and delusional perception, respectively. Although a number of
      recent studies tend to explain FRS in terms of neurobiological and
      neuropsychological processes, the origin of these symptoms still remains unknown.
      In this paper, we explore the subjective experience of patients with the
      following two FRS: (1) "made" impulses and (2) "made" volitional acts. METHOD:
      The method applied for the study of two FRS consists first in the overview of
      psychiatric and philosophical literature and second in the further investigation
      of subjective experience in patients with FRS. Psychopathological and
      phenomenological aspects of FRS are discussed by means of patient cases. RESULTS:
      We discovered a profound transformation of intentionality and agency in
      schizophrenia patients with body-affecting FRS. This concept offers an insight
      into the interrelatedness between particular FRS. CONCLUSION: We propose that the
      subjective experience of schizophrenia patients with body-affecting FRS is rooted
      in the disturbance of intentionality and diminished sense of agency. This
      theoretical account of body-affecting FRS will open up new directions in both
      phenomenological and neurobiological psychiatric research.

PMID- 24019933
TI  - Post-proliferative immature radial glial cells female-specifically express
      aromatase in the medaka optic tectum.
AB  - Aromatase, the key enzyme responsible for estrogen biosynthesis, is present in
      the brain of all vertebrates. Much evidence has accumulated that aromatase is
      highly and exclusively expressed in proliferating mature radial glial cells in
      the brain of teleost fish even in adulthood, unlike in other vertebrates.
      However, the physiological significance of this expression remains unknown. We
      recently found that aromatase is female-specifically expressed in the optic
      tectum of adult medaka fish. In the present study, we demonstrated that, contrary
      to the accepted view of the teleost brain, female-specific aromatase-expressing
      cells in the medaka optic tectum represent a transient subset of post
      proliferative immature radial glial cells in the neural stem cell lineage. This
      finding led us to hypothesize that female-specific aromatase expression and
      consequent estrogen production causes some sex difference in the life cycle of
      tectal cells. As expected, the female tectum exhibited higher expression of genes
      indicative of cell proliferation and radial glial maturation and lower expression
      of an anti-apoptotic gene than did the male tectum, suggesting a female-biased
      acceleration of the cell life cycle. Complicating the interpretation of this
      result, however, is the additional observation that estrogen administration
      masculinized the expression of these genes in the optic tectum, while
      simultaneously stimulating aromatase expression. Taken together, these results
      provide evidence that a unique subpopulation of neural stem cells female
      specifically express aromatase in the optic tectum and suggest that this
      aromatase expression and resultant estrogen synthesis have an impact on the life
      cycle of tectal cells, whether stimulatory or inhibitory. 

PMID- 24019934
TI  - Beetroot-pigment-derived colorimetric sensor for detection of calcium
      dipicolinate in bacterial spores.
AB  - In this proof-of-concept study, we describe the use of the main red beet pigment
      betanin for the quantification of calcium dipicolinate in bacterial spores,
      including Bacillus anthracis. In the presence of europium(III) ions, betanin is
      converted to a water-soluble, non-luminescent orange 1?1 complex with a stability
      constant of 1.4 * 10(5) L mol(-1). The addition of calcium dipicolinate, largely
      found in bacterial spores, changes the color of the aqueous solution of
      [Eu(Bn)(+)] from orange to magenta. The limit of detection (LOD) of calcium
      dipicolinate is around 2.0 * 10(-6) mol L(-1) and the LOD determined for both
      spores, B. cereus and B. anthracis, is (1.1 +/- 0.3)* 10(6) spores mL(-1). This
      simple, green, fast and low cost colorimetric assay was selective for calcium
      dipicolinate when compared to several analogous compounds. The importance of this
      work relies on the potential use of betalains, raw natural pigments, as
      colorimetric sensors for biological applications.

PMID- 24019936
TI  - Production of Trametes pubescens laccase under submerged and semi-solid culture
      conditions on agro-industrial wastes.
AB  - Laccases are copper-containing enzymes involved in the degradation of
      lignocellulosic materials and used in the treatment of phenol-containing
      wastewater. In this study we investigated the effect of culture conditions, i.e.
      submerged or semi-solid, and copper supplementation on laccase production by
      Trametespubescens grown on coffee husk, soybean pod husk, or cedar sawdust. The
      highest specific laccase activity was achieved when the culture was conducted
      under submerged conditions supplemented with copper (5 mM), and using coffee husk
      as substrate. The crude extracts presented two laccase isoforms with molecular
      mass of 120 (Lac1) and 60 kDa (Lac2). Regardless of the substrate, enzymatic
      crude extract and purified fractions behaved similarly at different temperatures
      and pHs, most of them presented the maximum activity at 55  degrees C and a pH
      range between 2 and 3. In addition, they showed similar stability and electro
      chemical properties. At optimal culture conditions laccase activity was 7.69 +/-
      0.28 U mg(-1) of protein for the crude extract, and 0.08 +/- 0.001 and 2.86 +/-
      0.05 U mg(-1) of protein for Lac1 and Lac2, respectively. In summary, these
      results show the potential of coffee husk as an important and economical growth
      medium to produce laccase, offering a new alternative use for this common agro
      industrial byproduct.

PMID- 24019935
TI  - Adult hippocampal neurogenesis and mRNA expression are altered by perinatal
      arsenic exposure in mice and restored by brief exposure to enrichment.
AB  - Arsenic is a common and pervasive environmental contaminant found in drinking
      water in varying concentrations depending on region. Exposure to arsenic induces
      behavioral and cognitive deficits in both human populations and in rodent models.
      The Environmental Protection Agency (EPA) standard for the allotment of arsenic
      in drinking water is in the parts-per-billion range, yet our lab has shown that
      50 ppb arsenic exposure during development can have far-reaching consequences
      into adulthood, including deficits in learning and memory, which have been linked
      to altered adult neurogenesis. Given that the morphological impact of
      developmental arsenic exposure on the hippocampus is unknown, we sought to
      evaluate proliferation and differentiation of adult neural progenitor cells in
      the dentate gyrus after 50 ppb arsenic exposure throughout the perinatal period
      of development in mice (equivalent to all three trimesters in humans) using a
      BrdU pulse-chase assay. Proliferation of the neural progenitor population was
      decreased by 13% in arsenic-exposed mice, but was not significant. However, the
      number of differentiated cells was significantly decreased by 41% in arsenic
      exposed mice compared to controls. Brief, daily exposure to environmental
      enrichment significantly increased proliferation and differentiation in both
      control and arsenic-exposed animals. Expression levels of 31% of neurogenesis
      related genes including those involved in Alzheimer's disease, apoptosis,
      axonogenesis, growth, Notch signaling, and transcription factors were altered
      after arsenic exposure and restored after enrichment. Using a concentration
      previously considered safe by the EPA, perinatal arsenic exposure altered
      hippocampal morphology and gene expression, but did not inhibit the cellular
      neurogenic response to enrichment. It is possible that behavioral deficits
      observed during adulthood in animals exposed to arsenic during development derive
      from the lack of differentiated neural progenitor cells necessary for hippocampal
      dependent learning. This study is the first to determine the impact of arsenic
      exposure during development on adult hippocampal neurogenesis and related gene
      expression. 

PMID- 24019937
TI  - Effect of temperature on the rate of ageing: an experimental study of the blowfly
      Calliphora stygia.
AB  - All organisms age, the rate of which can be measured by demographic analysis of
      mortality rates. The rate of ageing is thermally sensitive in ectothermic
      invertebrates and we examined the effects of temperature on both demographic
      rates of ageing and on cellular senescence in the blowfly, Calliphora stygia. The
      short lifespan of these flies is advantageous for demographic measurements while
      their large body size permits individual-based biochemical characterisation.
      Blowflies maintained at temperatures from 12 degrees C to 34 degrees C had a five
      to six-fold decrease in maximum and average longevity, respectively. Mortality
      rates were best described by a two-phase Gompertz relation, which revealed the
      first-phase of ageing to be much more temperature sensitive than the second
      stage. Flies held at low temperatures had both a slower first-phase rate of
      ageing and a delayed onset of second-phase ageing, which significantly extended
      their longevity compared with those at high temperatures. Blowflies that were
      transferred from 29 degrees C to 15 degrees C had higher first-phase mortality
      rates than those of flies held at constant 15 degrees C, but their onset of
      second-phase ageing was deferred beyond that of flies held constantly at this
      temperature. The accumulation of fluorescent AGE pigment, a measure of cellular
      oxidative damage, increased steadily over time in all blowflies, irrespective of
      the temporal pattern of mortality. Pigment accumulated steadily during periods of
      'negligible senescence', as measured by minimal rate of mortality, and the rate
      of accumulation was significantly affected by temperature. Thus accumulation of
      AGE pigment is more representative of chronological age than a reflection of
      biological age or a cause of mortality. 

PMID- 24019938
TI  - Memory self-efficacy beliefs modulate brain activity when encoding real-world
      future intentions.
AB  - BACKGROUND: While the use of different cognitive strategies when encoding
      episodic memory information has been extensively investigated, modulation of
      brain activity by memory self-efficacy beliefs has not been studied yet.
      METHODOLOGY/PRINCIPAL FINDINGS: Sixteen young adults completed the prospective
      and retrospective metamemory questionnaire, providing individual subjective
      judgments of everyday memory function. The day after, using functional magnetic
      resonance imaging, the participants had to memorize real-world intentions (e.g.,
      return a book to the library), which were performed later on in a virtual
      environment. Participants also performed offline cognitive tasks evaluating
      executive functions, working memory, and attention. During encoding, activity was
      found in medial temporal lobe, left prefrontal cortex, medial parietal regions,
      occipital areas, and regions involved in (pre)motor processes. Based on results
      from the questionnaire, the group was split into low and high memory self
      efficacy believers. Comparison of encoding-related brain activity between the 2
      groups revealed that the low memory self-efficacy believers activated more the
      hippocampus bilaterally, right posterior parahippocampal cortex, precuneus, and
      left lateral temporal cortex. By contrast, more activity was found in dorsal
      anterior cingulate gyrus for the high-memory believers. In addition, the low
      memory believers performed more poorly at feature binding and (at trend)
      manipulating visuospatial information in working memory. CONCLUSION/SIGNIFICANCE:
      Overall, these findings indicate that memory self-efficacy beliefs modulate brain
      activity during intentional encoding. Low memory self-efficacy believers
      activated more brain areas involved in visuospatial operations such as the
      hippocampus. Possibly, this increase reflects attempts to compensate for poor
      performance of certain neurocognitive processes, such as feature binding. By
      contrast, high-memory believers seemed to rely more on executive-like processes
      involved in cognitive control.

PMID- 24019939
TI  - Huntingtin acts non cell-autonomously on hippocampal neurogenesis and controls
      anxiety-related behaviors in adult mouse.
AB  - Huntington's disease (HD) is a fatal neurodegenerative disease, characterized by
      motor defects and psychiatric symptoms, including mood disorders such as anxiety
      and depression. HD is caused by an abnormal polyglutamine (polyQ) expansion in
      the huntingtin (HTT) protein. The development and analysis of various mouse
      models that express pathogenic polyQ-HTT revealed a link between mutant HTT and
      the development of anxio-depressive behaviors and various hippocampal
      neurogenesis defects. However, it is unclear whether such phenotype is linked to
      alteration of HTT wild-type function in adults. Here, we report the analysis of a
      new mouse model in which HTT is inducibly deleted from adult mature cortical and
      hippocampal neurons using the CreER(T2)/Lox system. These mice present defects in
      both the survival and the dendritic arborization of hippocampal newborn neurons.
      Our data suggest that these non-cell autonomous effects are linked to defects in
      both BDNF transport and release upon HTT silencing in hippocampal neurons, and in
      BDNF/TrkB signaling. The controlled deletion of HTT also had anxiogenic-like
      effects. Our results implicate endogenous wild-type HTT in adult hippocampal
      neurogenesis and in the control of mood disorders. 

PMID- 24019940
TI  - Characterization of the structural and functional determinants of MANF/CDNF in
      Drosophila in vivo model.
AB  - Mammalian MANF and CDNF proteins are evolutionarily conserved neurotrophic
      factors that can protect and repair mammalian dopaminergic neurons in vivo. In
      Drosophila, the sole MANF protein (DmManf) is needed for the maintenance of
      dopaminergic neurites and dopamine levels. Although both secreted and
      intracellular roles for MANF and CDNF have been demonstrated, very little is
      known about the molecular mechanism of their action. Here, by using a transgenic
      rescue approach in the DmManf mutant background we show that only full-length
      MANF containing both the amino-terminal saposin-like and carboxy-terminal SAP
      domains can rescue the larval lethality of the DmManf mutant. Independent N- or C
      terminal domains of MANF, even when co-expressed together, fail to rescue.
      Deleting the signal peptide or mutating the CXXC motif in the C-terminal domain
      destroys the activity of full-length DmManf. Positively charged surface amino
      acids and the C-terminal endoplasmic reticulum retention signal are necessary for
      rescue of DmManf mutant lethality when DmManf is expressed in a restricted
      pattern. Furthermore, rescue experiments with non-ubiquitous expression reveals
      functional differences between the C-terminal domain of human MANF and CDNF.
      Finally, DmManf and its C-terminal domain rescue mammalian sympathetic neurons
      from toxin-induced apoptosis in vitro demonstrating functional similarity of the
      mammalian and fly proteins. Our study offers further insights into the functional
      conservation between invertebrate and mammalian MANF/CDNF proteins and reveals
      the importance of the C-terminal domain for MANF activity in vivo. 

PMID- 24019941
TI  - Computational analyses of an evolutionary arms race between mammalian immunity
      mediated by immunoglobulin A and its subversion by bacterial pathogens.
AB  - IgA is the predominant immunoglobulin isotype in mucosal tissues and external
      secretions, playing important roles both in defense against pathogens and in
      maintenance of commensal microbiota. Considering the complexity of its
      interactions with the surrounding environment, IgA is a likely target for
      diversifying or positive selection. To investigate this possibility, the action
      of natural selection on IgA was examined in depth with six different methods:
      CODEML from the PAML package and the SLAC, FEL, REL, MEME and FUBAR methods
      implemented in the Datamonkey webserver. In considering just primate IgA, these
      analyses show that diversifying selection targeted five positions of the Calpha1
      and Calpha2 domains of IgA. Extending the analysis to include other mammals
      identified 18 positively selected sites: ten in Calpha1, five in Calpha2 and
      three in Calpha3. All but one of these positions display variation in polarity
      and charge. Their structural locations suggest they indirectly influence the
      conformation of sites on IgA that are critical for interaction with host IgA
      receptors and also with proteins produced by mucosal pathogens that prevent their
      elimination by IgA-mediated effector mechanisms. Demonstrating the plasticity of
      IgA in the evolution of different groups of mammals, only two of the eighteen
      selected positions in all mammals are included in the five selected positions in
      primates. That IgA residues subject to positive selection impact sites targeted
      both by host receptors and subversive pathogen ligands highlights the
      evolutionary arms race playing out between mammals and pathogens, and further
      emphasizes the importance of IgA in protection against mucosal pathogens. 

PMID- 24019942
TI  - Genomic interaction profiles in breast cancer reveal altered chromatin
      architecture.
AB  - Gene transcription can be regulated by remote enhancer regions through chromosome
      looping either in cis or in trans. Cancer cells are characterized by wholesale
      changes in long-range gene interactions, but the role that these long-range
      interactions play in cancer progression and metastasis is not well understood. In
      this study, we used IGFBP3, a gene involved in breast cancer pathogenesis, as
      bait in a 4C-seq experiment comparing normal breast cells (HMEC) with two breast
      cancer cell lines (MCF7, an ER positive cell line, and MDA-MB-231, a triple
      negative cell line). The IGFBP3 long-range interaction profile was substantially
      altered in breast cancer. Many interactions seen in normal breast cells are lost
      and novel interactions appear in cancer lines. We found that in HMEC, the breast
      carcinoma amplified sequence gene family (BCAS) 1-4 were among the top 10 most
      significantly enriched regions of interaction with IGFBP3. 3D-FISH analysis
      indicated that the translocation-prone BCAS genes, which are located on
      chromosomes 1, 17, and 20, are in close physical proximity with IGFBP3 and each
      other in normal breast cells. We also found that epidermal growth factor receptor
      (EGFR), a gene implicated in tumorigenesis, interacts significantly with IGFBP3
      and that this interaction may play a role in their regulation. Breakpoint
      analysis suggests that when an IGFBP3 interacting region undergoes a
      translocation an additional interaction detectable by 4C is gained. Overall, our
      data from multiple lines of evidence suggest an important role for long-range
      chromosomal interactions in the pathogenesis of cancer. 

PMID- 24019943
TI  - Proteome mapping of adult zebrafish marrow neutrophils reveals partial cross
      species conservation to human peripheral neutrophils.
AB  - Neutrophil granulocytes are pivotal cells within the first line of host defense
      of the innate immune system. In this study, we have used a gel-based LC-MS/MS
      approach to explore the proteome of primary marrow neutrophils from adult
      zebrafish. The identified proteins originated from all major cellular
      compartments. Gene ontology analysis revealed significant association of proteins
      with different immune-related network and pathway maps. 75% of proteins
      identified in neutrophils were identified in neutrophils only when compared to
      neutrophil-free brain tissue. Moreover, cross-species comparison with human
      peripheral blood neutrophils showed partial conservation of immune-related
      proteins between human and zebrafish. This study provides the first zebrafish
      neutrophil proteome and may serve as a valuable resource for an understanding of
      neutrophil biology and innate immunity. 

PMID- 24019944
TI  - Basic amino acid mutations in the nuclear localization signal of hibiscus
      chlorotic ringspot virus p23 inhibit virus long distance movement.
AB  - The p23 is a unique protein in the Hibiscus chlorotic ringspot virus which
      belongs to Family Tombusviridae Genus Carmovirus. Our previous results showed
      that the p23 is indispensable for host-specific replication and is localized in
      the nucleus with a novel nuclear localization signal. To investigate additional
      function(s) of p23, mutations of basic amino acids lysine (K), arginine (R) and
      histidine (H) that abolish its nuclear localization, were introduced into a
      biologically active full-length cDNA clone p223 of HCRSV for testing its effects
      on virus replication and virus movement in vivo. Primer-specific reverse
      transcription-PCR was conducted to detect gene transcript level of p23 and viral
      coat protein separately. Virus replication and its coat protein expression were
      detected by fluorescent in situ hybridization and Western blot, respectively. The
      effect of p23 was further confirmed by using artificial microRNA inoculation
      mediated silencing. Results showed that the two mutants were able to replicate in
      protoplasts but unable to move from inoculated leaves to newly emerged leaves.
      Both the p23 and the CP genes of HCRSV were detected in the newly emerged leaves
      of infected plants but CP was not detected by Western blot and no symptom was
      observed on those leaves at 19 days post inoculation. This study demonstrates
      that when p23 is prevented from entering the nucleus, it results in restriction
      of virus long distance movement which in turn abrogates symptom expression in the
      newly emerged leaves. We conclude that the p23 protein of HCRSV is required for
      virus long distance movement. 

PMID- 24019945
TI  - Systematic analysis and prediction of pupylation sites in prokaryotic proteins.
AB  - Prokaryotic ubiquitin-like protein (Pup) is the first identified prokaryotic
      protein that is functionally analogous to ubiquitin. Recent studies have shed
      light on the Pup activation and conjugation to target proteins to be a signal for
      the selective degradation proteins in Mycobacterium tuberculosis (Mtb). By
      covalently conjugating the Pup, pupylation functions as a critical post
      translational modification (PTM) conserved in actinomycetes. Detecting pupylation
      sites is crucial and fundamental for understanding the molecular mechanisms of
      Pup. Yet comparative studies with other PTM suggest that the development of
      accurate and complete repertories of pupylation is still in its early stages.
      Unbiased screening for pupylation sites by experimental methods is time consuming
      and expensive; in silico prediction can provide highly potential candidates and
      reduce the number of potential candidates that require further in vivo or in
      vitro confirmation. Here, we present an effective classifier of PupPred for
      predicting pupylation sites, which shows better performance than existing
      classifiers. Importantly, this work not only investigates the sequential,
      structural and evolutionary hallmarks around pupylation sites but also compares
      the differences of pupylation and ubiquitylation from the environmental,
      conservative and functional characterization of substrates. These prediction and
      analysis results may be helpful for further experimental investigation of
      degradation proteins in prokaryotes. Finally, the PupPred server is available at
      http://bioinfo.ncu.edu.cn/PupPred.aspx. 

PMID- 24019946
TI  - Unraveling the evolution of the Atlantic cod's (Gadus morhua L.) alternative
      immune strategy.
AB  - Genes encoding the major histocompatibility complex (MHC) have been thought to
      play a vital role in the adaptive immune system in all vertebrates. The discovery
      that Atlantic cod (Gadus morhua) has lost important components of the MHC II
      pathway, accompanied by an unusually high number of MHC I genes, shed new light
      on the evolution and plasticity of the immune system of teleosts as well as in
      higher vertebrates. The overall aim of this study was to further investigate the
      highly expanded repertoire of MHC I genes using a cDNA approach to obtain
      sequence information of both the binding domains and the sorting signaling
      potential in the cytoplasmic tail. Here we report a novel combination of two
      endosomal sorting motifs, one tyrosine-based associated with exogenous peptide
      presentation by cross-presenting MHCI molecules, and one dileucine-based
      associated with normal MHC II functionality. The two signal motifs were
      identified in the cytoplasmic tail in a subset of the genes. This indicates that
      these genes have evolved MHC II-like functionality, allowing a more versatile use
      of MHC I through cross-presentation. Such an alternative immune strategy may have
      arisen through adaptive radiation and acquisition of new gene function as a
      response to changes in the habitat of its ancestral lineage. 

PMID- 24019947
TI  - Maternal vitamin D status in type 1 diabetic pregnancy: impact on neonatal
      vitamin D status and association with maternal glycaemic control.
AB  - OBJECTIVE: The first aim of this study was to assess 25-hydroxy vitamin D (25OHD)
      concentrations in women with type 1 diabetes (T1DM) during pregnancy, post
      delivery and also foetal (cord blood) 25OHD concentrations and to examine
      relationships between these. The second aim of the study was to investigate
      potential interactions between maternal body mass index (BMI) and foetal vitamin
      D status. A further study aim was to examine potential relationships between
      maternal 25OHD and glycosylated haemoglobin (HbA1c) throughout pregnancy.
      RESEARCH DESIGN AND METHODS: This was an observational study of 52 pregnant
      controls without diabetes and 65 pregnant women with T1DM in a university
      teaching hospital. Maternal serum 25OHD was measured serially throughout the
      pregnancy and post-delivery. Cord blood 25OHD was measured at delivery. 25OHD was
      measured by liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS:
      Vitamin D deficiency (25OHD <25 nmol/L) was apparent in both the T1DM subjects
      and controls at all 3 pregnancy trimesters. Vitamin D levels in all cord blood
      were <50 nmol/L. Maternal 25OHD correlated positively with cord 25OHD at all 3
      trimesters in the T1DM group (p=0.02; p<0.001; p<0.001). 25OHD levels within cord
      blood were significantly lower for women with diabetes classified as obese vs.
      normal weight at booking [normal weight BMI <25 kg/m(2) vs. obese BMI >30 kg/m(2)
      (nmol/L +/- SD); 19.93 +/- 11.15 vs. 13.73 +/- 4.74, p=0.026]. In the T1DM group,
      HbA1c at booking was significantly negatively correlated with maternal 25OHD at
      all 3 trimesters (p=0.004; p=0.001; p=0.05). CONCLUSION: In T1DM pregnancy, low
      vitamin D levels persist throughout gestation and post-delivery. Cord blood
      vitamin D levels correlate with those of the mother, and are significantly lower
      in obese women than in their normal weight counterparts. Maternal vitamin D
      levels exhibit a significant negative relationship with HbA1c levels, supporting
      a potential role for this vitamin in maintaining glycaemic control.

PMID- 24019948
TI  - Major differences between tumor and normal human cell fates after exposure to
      chemotherapeutic monofunctional alkylator.
AB  - The major dilemma of cancer chemotherapy has always been a double-edged sword,
      producing resistance in tumor cells and life-threatening destruction of
      nontumorigenic tissue. Glioblastoma is the most common form of primary brain
      tumor, with median survival at 14 months after surgery, radiation and
      temozolomide (monofunctional alkylator) therapy. Treatment failure is most often
      due to temozolomide-resistant tumor growth. The underlying basis for development
      of tumor cell resistance to temozolomide instead of death is not understood. Our
      current results demonstrate that both cervical carcinoma (HeLa MR) and
      glioblastoma (U251) tumor cells exposed to an equivalent chemotherapeutic
      concentration of a monofunctional alkylator undergo multiple cell cycles,
      maintenance of metabolic activity, and a prolonged time to death that involves
      accumulation of Apoptosis Inducing Factor (AIF) within the nucleus. A minority of
      the tumor cell population undergoes senescence, with minimal caspase cleavage.
      Surviving tumor cells are comprised of a very small subpopulation of individual
      cells that eventually resume proliferation, out of which resistant cells emerge.
      In contrast, normal human cells (MCF12A) exposed to a monofunctional alkylator
      undergo an immediate decrease in metabolic activity and subsequent senescence. A
      minority of the normal cell population undergoes cell death by the caspase
      cleavage pathway. All cytotoxic events occur within the first cell cycle in
      nontumorigenic cells. In summation, we have demonstrated that two different
      highly malignant tumor cell lines slowly undergo very altered cellular and
      temporal responses to chemotherapeutic monofunctional alkylation, as compared to
      rapid responses of normal cells. In the clinic, this produces resistance and
      growth of tumor cells, cytotoxicity of normal cells, and death of the patient. 

PMID- 24019949
TI  - A new approach to control the enigmatic activity of aldose reductase.
AB  - Aldose reductase (AR) is an NADPH-dependent reductase, which acts on a variety of
      hydrophilic as well as hydrophobic aldehydes. It is currently defined as the
      first enzyme in the so-called polyol pathway, in which glucose is transformed
      into sorbitol by AR and then to fructose by an NAD(+)-dependent dehydrogenase. An
      exaggerated flux of glucose through the polyol pathway (as can occur in diabetes)
      with the subsequent accumulation of sorbitol, was originally proposed as the
      basic event in the aethiology of secondary diabetic complications. For decades
      this has meant targeting the enzyme for a specific and strong inhibition.
      However, the ability of AR to reduce toxic alkenals and alkanals, which are
      products of oxidative stress, poses the question of whether AR might be better
      classified as a detoxifying enzyme, thus raising doubts as to the unequivocal
      advantages of inhibiting the enzyme. This paper provides evidence of the
      possibility for an effective intervention on AR activity through an intra-site
      differential inhibition. Examples of a new generation of aldose reductase
      "differential" inhibitors (ARDIs) are presented, which can preferentially inhibit
      the reduction of either hydrophilic or hydrophobic substrates. Some selected
      inhibitors are shown to preferentially inhibit enzyme activity on glucose or
      glyceraldehyde and 3-glutathionyl-4-hydroxy-nonanal, but are less effective in
      reducing 4-hydroxy-2-nonenal. We question the efficacy of D, L-glyceraldehyde,
      the substrate commonly used in in vitro inhibition AR studies, as an in vitro
      reference AR substrate when the aim of the investigation is to impair glucose
      reduction. 

PMID- 24019950
TI  - Characterization of the role of eIF4G in stimulating cap- and IRES-dependent
      translation in aplysia neurons.
AB  - The rate-limiting step(s) of translation in the nervous system have not been
      clearly identified. We have been examining this question in the cell body of the
      Aplysia sensory neuron, where translational regulation is important for the
      regulation of synaptic strength. In the present study, we examined the role of
      the adaptor protein eIF4G. We cloned Aplysia eIF4G (Ap4G) and Ap4G contains all
      the standard metazoan eIF4G protein-protein interaction domains. Overexpressing
      Ap4G in Aplysia sensory neurons caused an increase in both cap-dependent and
      internal ribosome entry site (IRES)-dependent translation using a previously
      characterized bicistronic fluorescent reporter. Unexpectedly, measurement of
      overall translation using the methionine analog, L-azidohomoalanine, revealed
      that overexpression of Ap4G did not lead to an increase in overall translation
      rates. Indeed, the effect of Ap4G on the bicistronic reporter depended on the
      presence of an upstream open reading frame (uORF) in the 5' UTR encoded by the
      vector. We have previously shown that Mnk strongly decreased cap-dependent
      translation and this depended on a putative 4G binding domain. Here we extend
      these results showing that even in the absence of the uORF, overexpression of Mnk
      strongly decreases cap-dependent translation and this depends on the Mnk binding
      site in eIF4G. Similarly, an increase in cap-dependent translation seen with
      overexpression of elongation factor 2 kinase did not depend on the uORF. Overall,
      we show that eIF4G is rate limiting for translation of an mRNA encoding an uORF,
      but is not generally a rate-limiting step for translation. 

PMID- 24019951
TI  - Time-optimized high-resolution readout-segmented diffusion tensor imaging.
AB  - Readout-segmented echo planar imaging with 2D navigator-based reacquisition is an
      uprising technique enabling the sampling of high-resolution diffusion images with
      reduced susceptibility artifacts. However, low signal from the small voxels and
      long scan times hamper the clinical applicability. Therefore, we introduce a
      regularization algorithm based on total variation that is applied directly on the
      entire diffusion tensor. The spatially varying regularization parameter is
      determined automatically dependent on spatial variations in signal-to-noise ratio
      thus, avoiding over- or under-regularization. Information about the noise
      distribution in the diffusion tensor is extracted from the diffusion weighted
      images by means of complex independent component analysis. Moreover, the
      combination of those features enables processing of the diffusion data absolutely
      user independent. Tractography from in vivo data and from a software phantom
      demonstrate the advantage of the spatially varying regularization compared to un
      regularized data with respect to parameters relevant for fiber-tracking such as
      Mean Fiber Length, Track Count, Volume and Voxel Count. Specifically, for in vivo
      data findings suggest that tractography results from the regularized diffusion
      tensor based on one measurement (16 min) generates results comparable to the un
      regularized data with three averages (48 min). This significant reduction in scan
      time renders high resolution (1 * 1 * 2.5 mm(3)) diffusion tensor imaging of the
      entire brain applicable in a clinical context.

PMID- 24019952
TI  - Human PPP1R26P1 functions as cis-repressive element in mouse Rb1.
AB  - The human retinoblastoma gene (RB1) is imprinted; the mouse Rb1 gene is not.
      Imprinted expression of RB1 is due to differential methylation of a CpG island
      (CpG85), which is located in the pseudogene PPP1R26P1 in intron 2 of RB1. CpG85
      serves as promoter for an alternative RB1 transcript, which is expressed from the
      unmethylated paternal allele only and is thought to suppress expression of the
      full-length RB1 transcript in cis. PPP1R26P1 contains another CpG island (CpG42),
      which is biallelically methylated. To determine the influence of PPP1R26P1 on RB1
      expression, we generated an in vitro murine embryonic stem cell model by
      introducing human PPP1R26P1 into mouse Rb1. Next generation bisulfite sequencing
      of CpG85 and CpG42 revealed differences in their susceptibility to DNA
      methylation, gaining methylation at a median level of 4% and 18%, respectively.
      We showed binding of RNA polymerase II at and transcription from the unmethylated
      CpG85 in PPP1R26P1 and observed reduced expression of full-length Rb1 from the
      targeted allele. Our results identify human PPP1R26P1 as a cis-repressive element
      and support a connection between retrotransposition of PPP1R26P1 into human RB1
      and the reduced expression of RB1 on the paternal allele. 

PMID- 24019953
TI  - Verbal shadowing and visual interference in spatial memory.
AB  - Spatial memory is thought to be organized along experienced views and allocentric
      reference axes. Memory access from different perspectives typically yields V
      patterns for egocentric encoding (monotonic decline in performance along with the
      angular deviation from the experienced perspectives) and W-patterns for axes
      encoding (better performance along parallel and orthogonal perspectives than
      along oblique perspectives). We showed that learning an object array with a
      verbal secondary task reduced W-patterns compared with learning without verbal
      shadowing. This suggests that axes encoding happened in a verbal format; for
      example, by rows and columns. Alternatively, general cognitive load from the
      secondary task prevented memorizing relative to a spatial axis. Independent of
      encoding, pointing with a surrounding room visible yielded stronger W-patterns
      compared with pointing with no room visible. This suggests that the visible room
      geometry interfered with the memorized room geometry. With verbal shadowing and
      without visual interference only V-patterns remained; otherwise, V- and W
      patterns were combined. Verbal encoding and visual interference explain when W
      patterns can be expected alongside V-patterns and thus can help in resolving
      different performance patterns in a wide range of experiments. 

PMID- 24019954
TI  - Low potency homeopathic remedies and allopathic herbal medicines: is there an
      overlap?
AB  - Classical homeopathy is based on the therapeutic application of highly diluted
      homeopathic stocks. The indications of such medicines are determined by proving,
      i.e. by applying the remedies in healthy subjects. However, there are several
      complex homeopathic medicinal products on the market with approved therapeutic
      indications. The efficacy of these medicines has been assessed in clinical trials
      on patients. There is no upper limit of dosing for such homeopathic remedies, and
      these products often contain undiluted mother tincture. The aim of our study was
      to compare an allopathic herbal medicine and a homeopathic product containing
      undiluted mother tincture based on the same plant. Two products (an allopathic
      herbal medicine and a homeopathic product) containing Vitex agnus-castus extract
      were analyzed by HPLC-DAD for their agnuside and casticin contents. The agnuside
      content of the allopathic product was approximately four times higher, while the
      amount of casticin was in the same order of magnitude. Our experiments revealed
      the presence of active ingredients in allopathic quantity in a homeopathic
      preparation, highlighting the controversy between the principles of classical and
      practice of contemporary homeopathy. According to the principles of classical
      homeopathy these remedies cannot be considered as homeopathic remedies but rather
      as (allopathic) herbal ones. This phenomenon necessitates a case-by-case approach
      towards the possible adverse effects and drug interactions of homeopathics in the
      daily medical practice. Homeopathic products containing active agents in
      allopathic doses should be treated the same way as allopathic medicines from the
      point of view of quality assurance and pharmacovigilance. 

PMID- 24019955
TI  - Characterization, polymorphism and selection of major histocompatibility complex
      (MHC) DAB genes in vulnerable Chinese egret (Egretta eulophotes).
AB  - The major histocompatibility complex (MHC) is an excellent molecular marker for
      the studies of evolutionary ecology and conservation genetics because it is a
      family of highly polymorphic genes that play a key role in vertebrate immune
      response. In this study, the functional genes of MHC Class II B (DAB) were
      isolated for the first time in a vulnerable species, the Chinese egret
      (Egrettaeulophotes). Using a full length DNA and cDNA produced by PCR and RACE
      methods, four potential MHC DAB loci were characterized in the genome of this
      egret and all four were expressed in liver and blood. At least four copies of the
      MHC gene complex were similar to two copies of the minimal essential MHC complex
      of chicken, but are less complex than the multiple copies expressed in passerine
      species. In MHC polymorphism, 19 alleles of exon 2 were isolated from 48
      individuals using PCR. No stop codons or frameshift mutations were found in any
      of the coding regions. The signatures of positive selection detected in potential
      peptide-binding regions by Bayesian analysis, suggesting that all of these genes
      were functional. These data will provide the fundamental basis for further
      studies to elucidate the mechanisms and significance of MHC molecular adaptation
      in vulnerable Chinese egret and other ardeids. 

PMID- 24019956
TI  - Socio-demographic and lifestyle-related characteristics associated with self
      reported any, daily and occasional smoking during pregnancy.
AB  - Smoking during pregnancy is a risk factor for various adverse birth outcomes. In
      order to develop effective interventions, insight is needed into the
      characteristics associated with pregnant women who smoke. Unknown is whether
      these characteristics differ for women who smoke daily and women who smoke
      occasionally. Our study sample, drawn from the DELIVER study (Sept 2009-March
      2011), consisted of 6107 pregnant women in primary care in the Netherlands who
      were up to 34 weeks pregnant. The associations of thirteen socio-demographic or
      lifestyle-related characteristics with 'any smoking', 'daily smoking' and
      'occasional smoking' during pregnancy were tested using multiple binary logistic
      regression with general estimating equations (GEE). Characteristics most strongly
      associated with any smoking were low education (OR 10.3; 95% confidence interval
      (CI) 7.0-15.4), being of Turkish ethnicity (OR 3.9; 95%CI 2.3-6.7) and having no
      partner (OR 3.7; 95%CI 2.3-6.0). Women of Dutch ethnicity were three times more
      likely to smoke than those from Dutch-speaking Caribbean countries and non
      religious women were much more likely to smoke than religious women. Low
      education was markedly more strongly associated with daily smoking than with
      occasional smoking (OR 20.3; 95%CI 13.2-31.3 versus OR 6.0; 95%CI 3.4-10.5).
      Daily smokers were more likely to be associated with other unfavorable lifestyle
      related characteristics, such as not taking folic acid, being underweight, and
      having had an unplanned pregnancy. There is still much potential for health gain
      with respect to smoking during pregnancy in the Netherlands. Daily and occasional
      smokers appear to differ in characteristics, and therefore possibly require
      different interventions. 

PMID- 24019957
TI  - Impact of thoracic injury on traumatic brain injury outcome.
AB  - BACKGROUND: To assessed the significance of thoracic injury on the 30-day
      mortality and outcome of traumatic brain injury (TBI). METHODS: TBI patients
      admitted to our department were retrospectively evaluated. We developed two
      prognostic models based on admission predictors with logistic regression analysis
      to assess the significance of thoracic injuries in determining the 30-day
      mortality and outcome. The internal validity of the models was evaluated with the
      bootstrap re-sampling technique. We also validated the models in an external
      series of 165 patients that collected from our center. Discriminative ability was
      evaluated with C statistic. Calibrative ability was assessed with the Hosmer
      Lemeshow test (H-L test). RESULTS: Among 505 TBI patients admitted, 102 (20.2%)
      had thoracic injuries. Patients with a PCS >= 6 had a 3.142 and 8.065 times
      higher odds of mortality and poor outcome compared with patients with a PCS <6,
      respectively. Any one-score increase of the TTS had a 1.193 times higher odds of
      a poor outcome (p = 0.017). The predictive model for mortality and 30-day
      functional outcome both had good accuracy (AUC: 0.875; 95% confidence interval
      [CI], 0.841-0.910 and AUC: 0.888; 95%CI, 0.860-0.916, respectively). Internal
      validation showed no over optimism in any of the two models' predictive C
      statistics (C statistic 0.872 for 30-day mortality and C statistic 0.884 for the
      30-day neurological outcome). The external validation confirmed the
      discriminatory ability of these models (C statistic 0.949 (95%CI: 0.919-0.980)
      for 30-day mortality and C statistic 0.915 (95%CI: 0.868-0.963) for the 30-day
      neurological outcome). The calibration was also good for patients from the
      validation population (H-L test p>0.05). CONCLUSION: Thoracic injury diagnosed by
      CT has a negative impact on the 30-day mortality and functional outcome of TBI
      patients. The extent of PC and the TTS are the predictors for TBI outcome.

PMID- 24019958
TI  - Identification of fat mass and obesity associated (FTO) protein expression in
      cardiomyocytes: regulation by leptin and its contribution to leptin-induced
      hypertrophy.
AB  - The recently-identified fat mass and obesity-associated (FTO) protein is
      associated with various physiological functions including energy and body weight
      regulation. Ubiquitously expressed, FTO was identified in heart homogenates
      although its function is unknown. We studied whether FTO is specifically
      expressed within the cardiac myocyte and its potential role pertaining to the
      hypertrophic effect of the adipokine leptin. Most experiments were performed
      using cultured neonatal rat cardiomyocytes which showed nuclei-specific FTO
      expression. Leptin significantly increased FTO expression which was associated
      with myocyte hypertrophy although both events were abrogated by FTO knockdown
      with siRNA. Administration of a leptin receptor antibody to either normal or
      obese rats significant reduced myocardial FTO protein expression. Responses in
      cardiomyocytes were accompanied by JAK2/STAT3 activation whereas JAK2/STAT3
      inhibition abolished these effects. Expression of the cut-like homeobox 1(CUX1)
      transcriptional factor was significantly increased by leptin although this was
      restricted to the cathepsin L-dependent, proteolytically-derived shorter p110CUX1
      isoform whereas the longer p200CUX1 protein was not significantly affected.
      Cathepsin L expression and activity were both significantly increased by leptin
      whereas a cathepsin L peptide inhibitor or siRNA specific for CUX1 completely
      prevented the leptin-induced increase in FTO expression. The cathepsin L peptide
      inhibitor or siRNA-induced knockdown of either CUX1 or FTO abrogated the
      hypertrophic response to leptin. Two other pro-hypertrophic factors, endothelin-1
      or angiotensin II had no effect on FTO expression and FTO knockdown did not alter
      the hypertrophic response to either agent. This study demonstrates leptin-induced
      FTO upregulation in cardiomyocytes via JAK2/STAT3- dependent CUX1 upregulation
      and suggests an FTO regulatory function of leptin. It also demonstrates for the
      first time a functional role of FTO in the cardiomyocyte. 

PMID- 24019959
TI  - Proprioception is robust under external forces.
AB  - Information from cutaneous, muscle and joint receptors is combined with efferent
      information to create a reliable percept of the configuration of our body
      (proprioception). We exposed the hand to several horizontal force fields to
      examine whether external forces influence this percept. In an end-point task
      subjects reached visually presented positions with their unseen hand. In a vector
      reproduction task, subjects had to judge a distance and direction visually and
      reproduce the corresponding vector by moving the unseen hand. We found systematic
      individual errors in the reproduction of the end-points and vectors, but these
      errors did not vary systematically with the force fields. This suggests that
      human proprioception accounts for external forces applied to the hand when
      sensing the position of the hand in the horizontal plane. 

PMID- 24019960
TI  - AutomiG, a biosensor to detect alterations in miRNA biogenesis and in small RNA
      silencing guided by perfect target complementarity.
AB  - Defects in miRNA biogenesis or activity are associated to development
      abnormalities and diseases. In Drosophila, miRNAs are predominantly loaded in
      Argonaute-1, which they guide for silencing of target RNAs. The miRNA pathway
      overlaps the RNAi pathway in this organism, as miRNAs may also associate with
      Argonaute-2, the mediator of RNAi. We set up a gene construct in which a single
      inducible promoter directs the expression of the GFP protein as well as two
      miRNAs perfectly matching the GFP sequences. We show that self-silencing of the
      resulting automiG gene requires Drosha, Pasha, Dicer-1, Dicer-2 and Argonaute-2
      loaded with the anti-GFP miRNAs. In contrast, self-silencing of the automiG gene
      does not involve Argonaute-1. Thus, automiG reports in vivo for both miRNA
      biogenesis and Ago-2 mediated silencing, providing a powerful biosensor to
      identify situations where miRNA or siRNA pathways are impaired. As a proof of
      concept, we used automiG as a biosensor to screen a chemical library and
      identified 29 molecules that strongly inhibit miRNA silencing, out of which 5
      also inhibit RNAi triggered by long double-stranded RNA. Finally, the automiG
      sensor is also self-silenced by the anti-GFP miRNAs in HeLa cells and might be
      easily used to identify factors involved in miRNA biogenesis and silencing guided
      by perfect target complementarity in mammals. 

PMID- 24019961
TI  - CSF1 is a novel p53 target gene whose protein product functions in a feed-forward
      manner to suppress apoptosis and enhance p53-mediated growth arrest.
AB  - The p53 tumor suppressor gene has a common polymorphism at codon 72 that alters
      its function. We previously reported that the proline 72 polymorphic variant of
      p53 (P72) demonstrates increased ability to transactivate a subset of genes,
      relative to arginine 72 (R72); one of these genes is macrophage colony
      stimulating factor (CSF1). At present, the mechanism(s) underlying the increased
      transcriptional activity of P72 toward genes like CSF1 have not been completely
      elucidated. Additionally, the consequences of increased transcription of genes
      like CSF1 by the P72 variant to the downstream p53 pathway are unknown. In this
      report, we address these issues. We show that the CSF1 gene contains a conserved
      binding site for p53, and interestingly that the P72 variant shows increased
      ability to bind to this site. Moreover, we show that increased CSF1/CSF1R
      signaling in P72 cells feeds back on the p53 pathway to enhance p53
      phosphorylation, levels, and transactivation of target genes, particularly the
      cyclin-dependent kinase inhibitor p21 (CDKN1A). This leads to an increase in p53
      mediated growth arrest, along with a concomitant decrease in apoptosis. Notably,
      the CSF1/CSF1R signaling axis is overexpressed in several epithelial cancers, and
      there is clinical evidence that this pathway plays a role in radio-resistance of
      some cancers. We show that cells expressing CSF1 and CSF1R are indeed radio
      resistant, and further, that this effect requires p53. These combined data are
      the first to implicate the CSF1/CSF1R pathway in the decision between p53
      mediated growth arrest and apoptosis. They are also the first to highlight a
      cytokine as influential in cell fate determined by p53 in epithelial cells.
      Finally, these data may explain the association of the P72 variant and the
      CSF1/CSF1R pathway with increased senescence and radio-resistance in some
      epithelial tumor types. 

PMID- 24019962
TI  - Experimental pathways towards developing a rotavirus reverse genetics system:
      synthetic full length rotavirus ssRNAs are neither infectious nor translated in
      permissive cells.
AB  - At present the ability to create rationally engineered mutant rotaviruses is
      limited because of the lack of a tractable helper virus-free reverse genetics
      system. Using the cell culture adapted bovine RV RF strain (G6P6 [1]), we have
      attempted to recover infectious RV by co-transfecting in vitro transcribed ssRNAs
      which are identical in sequence to the positive sense strand of each of the 11
      dsRNA genomic segments of the RF strain. The RNAs were produced either from cDNAs
      cloned by a target sequence-independent procedure, or from purified double
      layered RV particles (DLPs). We have validated their translational function by in
      vitro synthesis of (35)S-labelled proteins in rabbit reticulocyte lysates; all 11
      proteins encoded by the RV genome were expressed. Transfection experiments with
      DLP- or cDNA-derived ssRNAs suggested that the RNAs do not act independently as
      mRNAs for protein synthesis, once delivered into various mammalian cell lines,
      and exhibit cytotoxicity. Transfected RNAs were not infectious since a viral
      cytopathic effect was not observed after infection of MA104 cells with lysates
      from transfected cells. By contrast, an engineered mRNA encoding eGFP was
      expressed when transfected under identical conditions into the same cell lines.
      Co-expression of plasmids encoding NSP2 and NSP5 using a fowlpox T7 polymerase
      recombinant virus revealed viroplasm-like structure formation, but this did not
      enable the translation of transfected RV ssRNAs. Attempts to recover RV from
      ssRNAs transcribed intracellularly from transfected cDNAs were also unsuccessful
      and suggested that these RNAs were also not translated, in contrast to successful
      translation from a transfected cDNA encoding an eGFP mRNA. 

PMID- 24019963
TI  - Expression of TrkC receptors in the developing brain of the Monodelphis opossum
      and its effect on the development of cortical cells.
AB  - In this study, we investigated the distribution, localization and several various
      functions of TrkC receptors during development of the Monodelphisopossum brain.
      Western blotting analysis showed that two different forms of the TrkC receptor,
      the full-length receptor and one of its truncated forms, are abundantly expressed
      in the opossum brain. The expression of TrkC receptors was barely detected in the
      brain of newborn opossums. At postnatal day (P) 3, the expression of full-length
      TrkC remained at low levels, while moderate expression of the TrkC truncated form
      was detected. The expression levels of both forms of this protein gradually
      increased throughout development, peaking at P35. We found that in different
      neocortical areas located both at the rostral and caudal regions of the cortex,
      up to 98% of BrdU-labeled cells forming cortical layers (II-VI) had prominently
      expressed TrkC. To assess which developmental processes of cortical cells are
      regulated by TrkC receptors, three different shRNAs were constructed. The shRNAs
      were individually tested in transfected cortical progenitor cells grown on
      culture plates for 2 days. The effects of the shRNA-TrkC constructs were similar:
      blockade of TrkC receptors decreased the number of Ki67-positive and apoptotic
      cells, and it did not change the number of TUJ-positive neurons in vitro. Thus,
      the lack of TrkC receptors in cultured progenitor cells provided insight on the
      potential role of these receptors in the regulation of proliferation and cell
      survival but not in the differentiation of cortical cells. 

PMID- 24019964
TI  - Quantitative mapping of matrix content and distribution across the ligament-to
      bone insertion.
AB  - The interface between bone and connective tissues such as the Anterior Cruciate
      Ligament (ACL) constitutes a complex transition traversing multiple tissue
      regions, including non-calcified and calcified fibrocartilage, which integrates
      and enables load transfer between otherwise structurally and functionally
      distinct tissue types. The objective of this study was to investigate region
      dependent changes in collagen, proteoglycan and mineral distribution, as well as
      collagen orientation, across the ligament-to-bone insertion site using Fourier
      transform infrared spectroscopic imaging (FTIR-I). Insertion site-related
      differences in matrix content were also evaluated by comparing tibial and femoral
      entheses. Both region- and site-related changes were observed. Collagen content
      was higher in the ligament and bone regions, while decreasing across the
      fibrocartilage interface. Moreover, interfacial collagen fibrils were aligned
      parallel to the ligament-bone interface near the ligament region, assuming a more
      random orientation through the bulk of the interface. Proteoglycan content was
      uniform on average across the insertion, while its distribution was relatively
      less variable at the tibial compared to the femoral insertion. Mineral was only
      detected in the calcified interface region, and its content increased
      exponentially across the mineralized fibrocartilage region toward bone. In
      addition to new insights into matrix composition and organization across the
      complex multi-tissue junction, findings from this study provide critical
      benchmarks for the regeneration of soft tissue-to-bone interfaces and integrative
      soft tissue repair. 

PMID- 24019965
TI  - Voltage affects the dissociation rate constant of the m2 muscarinic receptor.
AB  - G-protein coupled receptors (GPCRs) comprise the largest protein family and
      mediate the vast majority of signal transduction processes in the body. Until
      recently GPCRs were not considered to be voltage dependent. Newly it was shown
      for several GPCRs that the first step in GPCR activation, the binding of agonist
      to the receptor, is voltage sensitive: Voltage shifts the receptor between two
      states that differ in their binding affinity. Here we show that this shift
      involves the rate constant of dissociation. We used the m2 muscarinic receptor
      (m2R) a prototypical GPCR and measured directly the dissociation of [(3)H]ACh
      from m2R expressed Xenopus oocytes. We show, for the first time, that the voltage
      dependent change in affinity is implemented by voltage shifting the receptor
      between two states that differ in their rate constant of dissociation.
      Furthermore, we provide evidence that suggest that the above shift is achieved by
      voltage regulating the coupling of the GPCR to its G protein. 

PMID- 24019966
TI  - The relationship between hypomagnesemia, metformin therapy and cardiovascular
      disease complicating type 2 diabetes: the Fremantle Diabetes Study.
AB  - BACKGROUND: Low serum magnesium concentrations have been associated with
      cardiovascular disease risk and outcomes in some general population studies but
      there are no equivalent studies in diabetes. Metformin may have cardiovascular
      benefits beyond blood glucose lowering in type 2 diabetes but its association
      with hypomagnesemia appears paradoxical. The aim of this study was to examine
      relationships between metformin therapy, magnesium homoeostasis and
      cardiovascular disease in well-characterized type 2 patients from the community.
      METHODS AND FINDINGS: We studied 940 non-insulin-treated patients (mean +/- SD
      age 63.4 +/- 11.6 years, 49.0% males) from the longitudinal observational
      Fremantle Diabetes Study Phase I (FDS1) who were followed for 12.3 +/- 5.3 years.
      Baseline serum magnesium was measured using stored sera. Multivariate methods
      were used to determine associates of prevalent and incident coronary heart
      disease (CHD) and cerebrovascular disease (CVD) as ascertained from self-report
      and linked morbidity/mortality databases. 19% of patients were hypomagnesemic
      (serum magnesium <0.70 mmol/L). Patients on metformin, alone or combined with a
      sulfonylurea, had lower serum magnesium concentrations than those on diet alone
      (P<0.05). There were no independent associations between serum magnesium or
      metformin therapy and either CHD or CVD at baseline. Incident CVD, but not CHD,
      was independently and inversely associated with serum magnesium (hazard ratio
      (95% CI) 0.28 (0.11-0.74); P=0.010), but metformin therapy was not a significant
      variable in these models. CONCLUSIONS: Since hypomagnesemia appears to be an
      independent risk factor for CVD complicating type 2 diabetes, the value of
      replacement therapy should be investigated further, especially in patients at
      high CVD risk.

PMID- 24019967
TI  - Pinellia pedatisecta agglutinin targets drug resistant K562/ADR leukemia cells
      through binding with sarcolemmal membrane associated protein and enhancing
      macrophage phagocytosis.
AB  - Pinelliapedatisecta agglutinin (PPA) has previously been used in labeling
      fractions of myeloid leukemia cells in our laboratory. We report here that a
      bacterial expressed recombinant PPA domain b tagged with soluble coxsackie and
      adenovirus receptor (sCAR-PPAb) preferentially recognized drug resistant cancer
      cells K562/ADR and H460/5Fu, as compared to their parental cell lines.
      Pretreatment of K562/ADR cells with sCAR-PPAb significantly enhanced phagocytosis
      of K562/ADR by macrophages in vivo. Meanwhile, in a K562/ADR xenograft model,
      intratumoral injection of sCAR-PPAb induced macrophage infiltration and
      phagocytosis. Furthermore, immunoprecipitation, mass spectrometry and Western
      blot identified the membrane target of PPA on K562/ADR as sarcolemmal membrane
      associated protein (SLMAP). An antibody against SLMAP significantly promoted the
      phagocytosis of K562/ADR by macrophages in vitro. These findings suggest that PPA
      not only could be developed into a novel agent that can detect drug resistant
      cancer cells and predict chemotherapy outcome, but also it has potential value in
      immunotherapy against drug resistant cancer cells through inducing the
      tumoricidal activity of macrophages. 

PMID- 24019968
TI  - Organized emergence of multiple-generations of teeth in snakes is dysregulated by
      activation of Wnt/beta-catenin signalling.
AB  - In contrast to mammals, most reptiles constantly regenerate their teeth. In the
      snake, the epithelial dental lamina ends in a successional lamina, which
      proliferates and elongates forming multiple tooth generations, all linked by a
      permanent dental lamina. To investigate the mechanisms used to control the
      initiation of new tooth germs in an ordered sequential pattern we utilized the
      polyphodont (multiple-generation) corn snake (Pantherophis guttatus). We observed
      that the dental lamina expressed the transcription factor Sox2, a multipotent
      stem cell marker, whereas the successional lamina cells expressed the
      transcription factor Lef1, a Wnt/beta-catenin pathway target gene. Activation of
      the Wnt/beta-catenin pathway in culture increased the number of developing tooth
      germs, in comparison to control untreated cultures. These additional tooth germs
      budded off from ectopic positions along the dental lamina, rather than in an
      ordered sequence from the successional lamina. Wnt/beta-catenin activation
      enhanced cell proliferation, particularly in normally non-odontogenic regions of
      the dental lamina, which widely expressed Lef1, restricting the Sox2 domain. This
      suggests an expansion of the successional lamina at the expense of the dental
      lamina. Activation of the Wnt/beta-catenin pathway in cultured snake dental
      organs, therefore, led to changes in proliferation and to the molecular pattern
      of the dental lamina, resulting in loss of the organised emergence of tooth
      germs. These results suggest that epithelial compartments are critical for the
      arrangement of organs that develop in sequence, and highlight the role of
      Wnt/beta-catenin signalling in such processes. 

PMID- 24019969
TI  - Hypotonic shock modulates Na(+) current via a Cl(-) and Ca(2+)/calmodulin
      dependent mechanism in alveolar epithelial cells.
AB  - Alveolar epithelial cells are involved in Na(+) absorption via the epithelial
      Na(+) channel (ENaC), an important process for maintaining an appropriate volume
      of liquid lining the respiratory epithelium and for lung oedema clearance. Here,
      we investigated how a 20% hypotonic shock modulates the ionic current in these
      cells. Polarized alveolar epithelial cells isolated from rat lungs were cultured
      on permeant filters and their electrophysiological properties recorded. A 20%
      bilateral hypotonic shock induced an immediate, but transient 52% rise in total
      transepithelial current and a 67% increase in the amiloride-sensitive current
      mediated by ENaC. Amiloride pre-treatment decreased the current rise after
      hypotonic shock, showing that ENaC current is involved in this response. Since
      Cl(-) transport is modulated by hypotonic shock, its contribution to the basal
      and hypotonic-induced transepithelial current was also assessed. Apical NPPB, a
      broad Cl(-) channel inhibitor and basolateral DIOA a potassium chloride co
      transporter (KCC) inhibitor reduced the total and ENaC currents, showing that
      transcellular Cl(-) transport plays a major role in that process. During
      hypotonic shock, a basolateral Cl(-) influx, partly inhibited by NPPB is
      essential for the hypotonic-induced current rise. Hypotonic shock promoted apical
      ATP secretion and increased intracellular Ca(2+). While apyrase, an ATP
      scavenger, did not inhibit the hypotonic shock current response, W7 a calmodulin
      antagonist completely prevented the hypotonic current rise. These results
      indicate that a basolateral Cl(-) influx as well as Ca(2+)/calmodulin, but not
      ATP, are involved in the acute transepithelial current rise elicited by hypotonic
      shock. 

PMID- 24019970
TI  - RNA-Seq reveals infection-related gene expression changes in Phytophthora
      capsici.
AB  - Phytophthora capsici is a soilborne plant pathogen capable of infecting a wide
      range of plants, including many solanaceous crops. However, genetic resistance
      and fungicides often fail to manage P. capsici due to limited knowledge on the
      molecular biology and basis of P. capsici pathogenicity. To begin to rectify this
      situation, Illumina RNA-Seq was used to perform massively parallel sequencing of
      three cDNA samples derived from P. capsici mycelia (MY), zoospores (ZO) and
      germinating cysts with germ tubes (GC). Over 11 million reads were generated for
      each cDNA library analyzed. After read mapping to the gene models of P. capsici
      reference genome, 13,901, 14,633 and 14,695 putative genes were identified from
      the reads of the MY, ZO and GC libraries, respectively. Comparative analysis
      between two of samples showed major differences between the expressed gene
      content of MY, ZO and GC stages. A large number of genes associated with specific
      stages and pathogenicity were identified, including 98 predicted effector genes.
      The transcriptional levels of 19 effector genes during the developmental and host
      infection stages of P. capsici were validated by RT-PCR. Ectopic expression in
      Nicotiana benthamiana showed that P. capsici RXLR and Crinkler effectors can
      suppress host cell death triggered by diverse elicitors including P. capsici
      elicitin and NLP effectors. This study provides a first look at the transcriptome
      and effector arsenal of P. capsici during the important pre-infection stages. 

PMID- 24019971
TI  - Endo-MitoEGFP mice: a novel transgenic mouse with fluorescently marked
      mitochondria in microvascular endothelial cells.
AB  - Blood vessel-specific fluorescent transgenic mice are excellent tools to study
      the development of the vasculature and angiogenic processes. There is growing
      interest in the biological processes relevant to endothelial cells but limited
      tools exist to selectively evaluate subcellular functions of this cell type in
      vivo. Here, we report a novel transgenic animal model that expresses
      mitochondrially targeted enhanced green fluorescent protein (EGFP) via the Hb9
      promoter, a homeobox transcription factor with limited known involvement in the
      vasculature. Random integration of the transgene, containing the entire mouse Hb9
      promoter, was found to be expressed in a variety of vascularised tissues. Further
      inspection revealed that Mito-EGFP localizes to the endothelial cells (ECs) of a
      subset of microvascular blood vessels, especially in the central nervous system
      (CNS), heart, spleen, thymus, lymph nodes and skin. We demonstrate the utility of
      this novel transgenic mouse, named Endo-MitoEGFP, in the detection, imaging, and
      isolation of microvascular ECs and evaluation of EC mitochondrial function
      isolated from adult animals. These transgenic mice will be useful to studies of
      ECs in development, physiology, and pathology. 

PMID- 24019972
TI  - Adenoviral-mediated placental gene transfer of IGF-1 corrects placental
      insufficiency via enhanced placental glucose transport mechanisms.
AB  - Previous work in our laboratory demonstrated that over-expression of human
      insulin-like growth factor -1 (hIGF-1) in the placenta corrects fetal weight
      deficits in mouse, rat, and rabbit models of intrauterine growth restriction
      without changes in placental weight. The underlying mechanisms of this effect
      have not been elucidated. To investigate the effect of intra-placental IGF-1 over
      expression on placental function we examined glucose transporter expression and
      localization in both a mouse model of IUGR and a model of human trophoblast, the
      BeWo Choriocarcinoma cell line. METHODS: At gestational day 18, animals were
      divided into four groups; sham-operated controls, uterine artery branch ligation
      (UABL), UABL+Ad-hIGF-1 (10(8) PFU), UABL+Ad-LacZ (10(8) PFU). At gestational day
      20, pups and placentas were harvested by C-section. For human studies, BeWo
      choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were
      incubated in serum-free control media +/- Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs
      of 10?1 and 100?1 were utilized. The RNA, protein expression and localization of
      glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and
      immunohistochemistry. RESULTS: In both the mouse placenta and BeWo, GLUT1
      regulation was linked to altered protein localization. GLUT3, localized to the
      mouse fetal endothelial cells, was reduced in placental insufficiency but
      maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced
      in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human
      systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not
      reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization.
      CONCLUSION: Enhanced GLUT isoform transporter expression and relocalization to
      the membrane may be an important mechanism in Ad-hIGF-1mediated correction of
      placental insufficiency.

PMID- 24019973
TI  - Inhibition of STAT3 by niclosamide synergizes with erlotinib against head and
      neck cancer.
AB  - Epidermal growth factor receptor (EGFR) is extensively expressed in head and neck
      cancer. However, EGFR-targeted therapy has only modest efficacy in head and neck
      cancer, through mechanisms that are not fully understood. Here, we found that
      inhibition of EGFR by erlotinib stimulated phosphorylation and activation of
      STAT3 leading to increased Bcl2/Bcl-XL expression in head and neck cancer cells,
      which may dampen the therapeutic efficacy of erlotinib against head and neck
      cancer. Erlotinib-enhanced STAT3 phosphorylation results, at least in part, from
      suppression of its physiological phosphatase, PTPMeg2. Specific knockdown of
      STAT3 by RNA interference significantly sensitized head and neck cancer cells to
      erlotinib treatment. Pharmacological inhibition of STAT3 by niclosamide not only
      blocked erlotinib-stimulated STAT3 phosphorylation but also synergistically
      repressed head and neck cancer growth in vitro and in vivo. Combined inhibition
      of EGFR and STAT3 by erlotinib and niclosamide more effectively induced apoptosis
      in tumor tissues without toxicity for normal tissues. Based on our findings,
      treatment with erlotinib combined with niclosamide may offer an effective
      therapeutic approach to improve the prognosis of head and neck cancer. 

PMID- 24019974
TI  - Provider continuity prior to the diagnosis of advanced lung cancer and end-of
      life care.
AB  - BACKGROUND: Little is known about the effect of provider continuity prior to the
      diagnosis of advanced lung cancer and end-of-life care. METHODS: Retrospective
      analysis of 69,247 Medicare beneficiaries aged 67 years or older diagnosed with
      Stage IIIB or IV lung cancer between January 1, 1993 and December 31, 2005 who
      died within two years of diagnosis. We examined visit patterns to a primary care
      physician (PCP) and/or any provider one year prior to the diagnosis of advanced
      lung cancer as measures of continuity of care. Outcome measures were
      hospitalization, ICU use and chemotherapy use during the last month of life, and
      hospice use during the last week of life. RESULTS: Seeing a PCP or any provider
      in the year prior to the diagnosis of advanced lung cancer increased the
      likelihood of hospitalization, ICU care, chemotherapy and hospice use during the
      end of life. Patients with 1-3, 4-7 or >7 visits to their PCP in the year prior
      to the diagnosis of lung cancer had 1.0 (reference), 1.08 (95% CI; 1.04-1.13),
      and 1.14 (95% CI; 1.08-1.19) odds of hospitalization during the last month of
      life, respectively. Odds of hospice use during the last week of life were higher
      in patients with visits to multiple PCPs (OR 1.10: 95% CI; 1.06-1.15) compared to
      those whose visits were all to the same PCP. CONCLUSION: Provider continuity in
      the year prior to the diagnosis of advanced lung cancer was not associated with
      lower use of aggressive care during end of life. Our study did not have
      information on patient preferences and result should be interpreted accordingly.

PMID- 24019975
TI  - The color of debt: racial disparities in anticipated medical student debt in the
      United States.
AB  - CONTEXT: The cost of American medical education has increased substantially over
      the past decade. Given racial/ethnic inequalities in access to financial
      resources, it is plausible that increases in student debt burden resulting from
      these increases in cost may not be borne equally. OBJECTIVE: To evaluate
      racial/ethnic disparities in medical student debt. DESIGN SETTING AND
      PARTICIPANTS: Authors collected self-reported data from a non-representative
      sample of 2414 medical students enrolled at 111/159 accredited US medical schools
      between December 1(st) 2010 and March 27(th) 2011. After weighting for
      representativeness by race and class year and calculating crude anticipated debt
      by racial/ethnic category, authors fit multivariable regression models of debt by
      race/ethnicity adjusted for potential confounders. MAIN OUTCOME MEASURES:
      Anticipated educational debt upon graduation greater than $150,000. RESULTS:
      62.1% of medical students anticipated debt in excess of $150,000 upon graduation.
      The proportion of Blacks, Whites, Hispanics, and Asians reporting anticipated
      educational debt in excess of $150,000 was 77.3%, 65.1%, 57.2% and 50.2%,
      respectively. Both Black and White medical students demonstrated a significantly
      higher likelihood of anticipated debt in excess of $150,000 when compared to
      Asians [Blacks (OR=2.7, 1.3-5.6), Whites (OR=1.7, 1.3-2.2)] in adjusted models.
      CONCLUSION: Black medical students had significantly higher anticipated debt than
      Asian students. This finding has implications for understanding differential
      enrollment among minority groups in US medical schools.

PMID- 24019976
TI  - Contrasting food web factor and body size relationships with Hg and Se
      concentrations in marine biota.
AB  - Marine fish and shellfish are primary sources of human exposure to mercury, a
      potentially toxic metal, and selenium, an essential element that may protect
      against mercury bioaccumulation and toxicity. Yet we lack a thorough
      understanding of Hg and Se patterns in common marine taxa, particularly those
      that are commercially important, and how food web and body size factors differ in
      their influence on Hg and Se patterns. We compared Hg and Se content among marine
      fish and invertebrate taxa collected from Long Island, NY, and examined
      associations between Hg, Se, body length, trophic level (measured by delta(15)N)
      and degree of pelagic feeding (measured by delta(13)C). Finfish, particularly
      shark, had high Hg content whereas bivalves generally had high Se content. Both
      taxonomic differences and variability were larger for Hg than Se, and Hg content
      explained most of the variation in Hg:Se molar ratios among taxa. Finally, Hg was
      more strongly associated with length and trophic level across taxa than Se,
      consistent with a greater degree of Hg bioaccumulation in the body over time, and
      biomagnification through the food web, respectively. Overall, our findings
      indicate distinct taxonomic and ecological Hg and Se patterns in commercially
      important marine biota, and these patterns have nutritional and toxicological
      implications for seafood-consuming wildlife and humans. 

PMID- 24019977
TI  - The N-terminus of Vps74p is essential for the retention of glycosyltransferases
      in the Golgi but not for the modulation of apical polarized growth in
      Saccharomyces cerevisiae.
AB  - Vps74p is a member of the PtdIns(4)P-binding protein family. Vps74p interacts
      with Golgi-resident glycosyltransferases and the coat protein COPI complex to
      modulate Golgi retention of glycosyltransferases and with the PtdIns(4)P
      phosphatase Sac1p to modulate PtdIns(4)P homeostasis at the Golgi. Genetic
      analysis has shown that Vps74p is required for the formation of abnormal
      elongated buds in cdc34-2 cells. The C-terminal region of Vps74p is required for
      Vps74p multimerization, Golgi localization, and glycosyltransferase interactions;
      however, the functional significance of the N-terminal region and three putative
      phosphorylation sites of Vps74p have not been well characterized. In this study,
      we demonstrate that Vps74p executes multiple cellular functions using different
      domains. We found that the N-terminal 66 amino acids of Vps74p are dispensable
      for its Golgi localization and modulation of cell wall integrity but are required
      for glycosyltransferase retention and glycoprotein processing. Deletion of the N
      terminal 90 amino acids, but not the 66 amino acids, of Vps74p impaired its
      ability to restore the elongated bud phenotype in cdc34-2/vps74Delta cells.
      Deletion of Sac1p and Arf1p also specifically reduced the abnormal elongated bud
      phenotype in cdc34-2 cells. Furthermore, we found that three N-terminal
      phosphorylation sites contribute to rapamycin hypersensitivity, although these
      phosphorylation residues are not involved in Vps74p localization, ability to
      modulate glycosyltransferase retention, or elongated bud formation in cdc34-2
      cells. Thus, we propose that Vps74p may use different domains to interact with
      specific effectors thereby differentially modulating a variety of cellular
      functions. 

PMID- 24019978
TI  - Cataract-causing mutation of human connexin 46 impairs gap junction, but
      increases hemichannel function and cell death.
AB  - Connexin channels play a critical role in maintaining metabolic homeostasis and
      transparency of the lens. Mutations in connexin genes are linked to congenital
      cataracts in humans. The G143R missense mutation on connexin (Cx) 46 was recently
      reported to be associated with congenital Coppock cataracts. Here, we showed that
      the G143R mutation decreased Cx46 gap junctional coupling in a dominant negative
      manner; however, it significantly increased gap junctional plaques. The G143R
      mutant also increased hemichannel activity, inversely correlated with the level
      of Cx46 protein on the cell surface. The interaction between cytoplasmic loop
      domain and C-terminus has been shown to be involved in gating of connexin
      channels. Interestingly, the G143R mutation enhanced the interaction between
      intracellular loop and Cx46. Furthermore, this mutation decreased cell viability
      and the resistance of the cells to oxidative stress, primarily due to the
      increased hemichannel function. Together, these results suggest that mutation of
      this highly conserved residue on the cytoplasmic loop domain of Cx46 enhances its
      interaction with the C-terminus, resulting in a reduction of gap junction channel
      function, but increased hemichannel function. This combination leads to the
      development of human congenital cataracts. 

PMID- 24019979
TI  - Cryptococcus gattii in the United States: genotypic diversity of human and
      veterinary isolates.
AB  - BACKGROUND: Cryptococcusgattii infections are being reported in the United States
      (US) with increasing frequency. Initially, US reports were primarily associated
      with an ongoing C. gattii outbreak in the Pacific Northwest (PNW) states of
      Washington and Oregon, starting in 2004. However, reports of C. gattii infections
      in patients from other US states have been increasing since 2009. Whether this is
      due to increasing frequency of disease, greater recognition within the clinical
      community, or both is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: During
      2005-2013, a total of 273 C. gattii isolates from human and veterinary sources in
      16 US states were collected. Of these, 214 (78%) were from the Pacific Northwest
      (PNW) and comprised primarily the clonal C. gattii genotypes VGIIa (64%), VGIIc
      (21%) and VGIIb (9%). The 59 isolates from outside the PNW were predominantly
      molecular types VGIII (44%) and VGI (41%). Genotyping using multilocus sequence
      typing revealed small clusters, including a cluster of VGI isolates from the
      southeastern US, and an unrelated cluster of VGI isolates and a large cluster of
      VGIII isolates from California. Most of the isolates were mating type MATalpha,
      including all of the VGII isolates, but one VGI and three VGIII isolates were
      mating type MATa. CONCLUSIONS/SIGNIFICANCE: We provide the most comprehensive
      report to date of genotypic diversity of US C. gattii isolates both inside and
      outside of the PNW. C. gattii may have multiple endemic regions in the US,
      including a previously-unrecognized endemic region in the southeast. Regional
      clusters exist both in California and the Southeastern US. VGII strains
      associated with the PNW outbreak do not appear to have spread substantially
      beyond the PNW.

PMID- 24019980
TI  - Expression of SIRT1 and DBC1 is associated with poor prognosis of soft tissue
      sarcomas.
AB  - Recently, the roles of SIRT1 and deleted in breast cancer 1 (DBC1) in human
      cancer have been extensively studied and it has been demonstrated that they are
      involved in many human carcinomas. However, their clinical significance for soft
      tissue sarcomas has not been examined. In this study, we evaluated the expression
      and prognostic significance of the expression of SIRT1, DBC1, P53, beta-catenin,
      cyclin D1, and KI67 in 104 cases of soft-tissue sarcomas. RESULTS:
      Immunohistochemical expression of SIRT1, DBC1, P53, beta-catenin, and cyclin D1
      were seen in 71%, 74%, 53%, 48%, and 73% of sarcomas, respectively. The
      expression of SIRT1, DBC1, P53, beta-catenin, and cyclin D1 were significantly
      correlated with advanced clinicopathological parameters such as higher clinical
      stage, higher histological grade, increased mitotic counts, and distant
      metastasis. The expression of SIRT1, DBC1, P53, beta-catenin, cyclin D1, and KI67
      were significantly correlated with each other and positive expression of all of
      these predicted shorter overall survival and event-free survival by univariate
      analysis. Multivariate analysis revealed the expression of SIRT1 as an
      independent prognostic indicator for overall survival and event-free survival of
      sarcoma patients. In conclusion, this study demonstrates that SIRT1- and DBC1
      related pathways may be involved in the progression of soft-tissue sarcomas and
      can be used as clinically significant prognostic indicators for sarcoma patients.
      Moreover, the SIRT1- and DBC1-related pathways could be new therapeutic targets
      for the treatment of sarcomas.

PMID- 24019981
TI  - A forward genetic approach in Chlamydomonas reinhardtii as a strategy for
      exploring starch catabolism.
AB  - A screen was recently developed to study the mobilization of starch in the
      unicellular green alga Chlamydomonas reinhardtii. This screen relies on starch
      synthesis accumulation during nitrogen starvation followed by the supply of
      nitrogen and the switch to darkness. Hence multiple regulatory networks including
      those of nutrient starvation, cell cycle control and light to dark transitions
      are likely to impact the recovery of mutant candidates. In this paper we monitor
      the specificity of this mutant screen by characterizing the nature of the genes
      disrupted in the selected mutants. We show that one third of the mutants
      consisted of strains mutated in genes previously reported to be of paramount
      importance in starch catabolism such as those encoding beta-amylases, the maltose
      export protein, and branching enzyme I. The other mutants were defective for
      previously uncharacterized functions some of which are likely to define novel
      proteins affecting starch mobilization in green algae. 

PMID- 24019982
TI  - Combining phylogenetic and syntenic analyses for understanding the evolution of
      TCP ECE genes in eudicots.
AB  - TCP ECE genes encode transcription factors which have received much attention for
      their repeated recruitment in the control of floral symmetry in core eudicots,
      and more recently in monocots. Major duplications of TCP ECE genes have been
      described in core eudicots, but the evolutionary history of this gene family is
      unknown in basal eudicots. Reconstructing the phylogeny of ECE genes in basal
      eudicots will help set a framework for understanding the functional evolution of
      these genes. TCP ECE genes were sequenced in all major lineages of basal eudicots
      and Gunnera which belongs to the sister clade to all other core eudicots. We show
      that in these lineages they have a complex evolutionary history with repeated
      duplications. We estimate the timing of the two major duplications already
      identified in the core eudicots within a timeframe before the divergence of
      Gunnera and after the divergence of Proteales. We also use a synteny-based
      approach to examine the extent to which the expansion of TCP ECE genes in diverse
      eudicot lineages may be due to genome-wide duplications. The three major core
      eudicot specific clades share a number of collinear genes, and their common
      evolutionary history may have originated at the gamma event. Genomic comparisons
      in Arabidopsis thaliana and Solanumlycopersicum highlight their separate
      polyploid origin, with syntenic fragments with and without TCP ECE genes showing
      differential gene loss and genomic rearrangements. Comparison between recently
      available genomes from two basal eudicots Aquilegiacoerulea and Nelumbonucifera
      suggests that the two TCP ECE paralogs in these species are also derived from
      large-scale duplications. TCP ECE loci from basal eudicots share many features
      with the three main core eudicot loci, and allow us to infer the makeup of the
      ancestral eudicot locus. 

PMID- 24019983
TI  - Serum cytokine profiles associated with specific adjuvants used in a DNA prime
      protein boost vaccination strategy.
AB  - In recent years, heterologous prime-boost vaccines have been demonstrated to be
      an effective strategy for generating protective immunity, consisting of both
      humoral and cell-mediated immune responses against a variety of pathogens
      including HIV-1. Previous reports of preclinical and clinical studies have shown
      the enhanced immunogenicity of viral vector or DNA vaccination followed by
      heterologous protein boost, compared to using either prime or boost components
      alone. With such approaches, the selection of an adjuvant for inclusion in the
      protein boost component is expected to impact the immunogenicity and safety of a
      vaccine. In this study, we examined in a mouse model the serum cytokine and
      chemokine profiles for several candidate adjuvants: QS-21, Al(OH)3,
      monophosphoryl lipid A (MPLA) and ISCOMATRIXTM adjuvant, in the context of a
      previously tested pentavalent HIV-1 Env DNA prime-protein boost formulation, DP6
      001. Our data revealed that the candidate adjuvants in the context of the DP6-001
      formulation are characterized by unique serum cytokine and chemokine profiles.
      Such information will provide valuable guidance in the selection of an adjuvant
      for future AIDS vaccine development, with the ultimate goal of enhancing
      immunogenicity while minimizing reactogenicity associated with the use of an
      adjuvant. More significantly, results reported here will add to the knowledge on
      how to include an adjuvant in the context of a heterologous prime-protein boost
      vaccination strategy in general. 

PMID- 24019984
TI  - Non contiguous-finished genome sequence and description of Senegalemassilia
      anaerobia gen. nov., sp. nov.
AB  - Senegalemassilia anaerobia strain JC110(T) sp.nov. is the type strain of
      Senegalemassilia anaerobia gen. nov., sp. nov., the type species of a new genus
      within the Coriobacteriaceae family, Senegalemassilia gen. nov. This strain,
      whose genome is described here, was isolated from the fecal flora of a healthy
      Senegalese patient. S. anaerobia is a Gram-positive anaerobic coccobacillus. Here
      we describe the features of this organism, together with the complete genome
      sequence and annotation. The 2,383,131 bp long genome contains 1,932 protein
      coding and 58 RNA genes. 

PMID- 24019985
TI  - Non contiguous-finished genome sequence and description of Peptoniphilus obesi
      sp. nov.
AB  - Peptoniphilus obesi strain ph1(T) sp. nov., is the type strain of P. obesi sp.
      nov., a new species within the genus Peptoniphilus. This strain, whose genome is
      described here, was isolated from the fecal flora of a 26-year-old woman
      suffering from morbid obesity. P. obesi strain ph1(T) is a Gram-positive,
      obligate anaerobic coccus. Here we describe the features of this organism,
      together with the complete genome sequence and annotation. The 1,774,150 bp long
      genome (1 chromosome but no plasmid) contains 1,689 protein-coding and 29 RNA
      genes, including 5 rRNA genes. 

PMID- 24019986
TI  - Non contiguous-finished genome sequence and description of Peptoniphilus
      senegalensis sp. nov.
AB  - Peptoniphilus senegalensis strain JC140(T) sp. nov., is the type strain of P.
      senegalensis sp. nov., a new species within the genus Peptoniphilus. This strain,
      whose genome is described here, was isolated from the fecal flora of a healthy
      patient. P. senegalensis strain JC140(T) is an obligate Gram-positive anaerobic
      coccus. Here we describe the features of this organism, together with the
      complete genome sequence and annotation. The 1,840,641 bp long genome (1
      chromosome but no plasmid) exhibits a G+C content of 32.2% and contains 1,744
      protein-coding and 23 RNA genes, including 3 rRNA genes. 

PMID- 24019987
TI  - Metagenomes of tropical soil-derived anaerobic switchgrass-adapted consortia with
      and without iron.
AB  - Tropical forest soils decompose litter rapidly with frequent episodes of anoxia,
      making it likely that bacteria using alternate terminal electron acceptors (TEAs)
      such as iron play a large role in supporting decomposition under these
      conditions. The prevalence of many types of metabolism in litter deconstruction
      makes these soils useful templates for improving biofuel production. To
      investigate how iron availability affects decomposition, we cultivated feedstock
      adapted consortia (FACs) derived from iron-rich tropical forest soils accustomed
      to experiencing frequent episodes of anaerobic conditions and frequently
      fluctuating redox. One consortium was propagated under fermenting conditions,
      with switchgrass as the sole carbon source in minimal media (SG only FACs), and
      the other consortium was treated the same way but received poorly crystalline
      iron as an additional terminal electron acceptor (SG + Fe FACs). We sequenced the
      metagenomes of both consortia to a depth of about 150 Mb each, resulting in a
      coverage of 26* for the more diverse SG + Fe FACs, and 81* for the relatively
      less diverse SG only FACs. Both consortia were able to quickly grow on
      switchgrass, and the iron-amended consortium exhibited significantly higher
      microbial diversity than the unamended consortium. We found evidence of higher
      stress in the unamended FACs and increased sugar transport and utilization in the
      iron-amended FACs. This work provides metagenomic evidence that supplementation
      of alternative TEAs may improve feedstock deconstruction in biofuel production. 

PMID- 24019988
TI  - Non contiguous-finished genome sequence and description of Enterobacter
      massiliensis sp. nov.
AB  - Enterobacter massiliensis strain JC163(T) sp. nov. is the type strain of E.
      massiliensis sp. nov., a new species within the genus Enterobacter. This strain,
      whose genome is described here, was isolated from the fecal flora of a healthy
      Senegalese patient. E. massiliensis is an aerobic rod. Here we describe the
      features of this organism, together with the complete genome sequence and
      annotation. The 4,922,247 bp long genome (1 chromosome but no plasmid) exhibits a
      G+C content of 55.1% and contains 4,644 protein-coding and 80 RNA genes,
      including 5 rRNA genes. 

PMID- 24019989
TI  - Genome of the R-body producing marine alphaproteobacterium Labrenzia alexandrii
      type strain (DFL-11(T)).
AB  - Labrenzia alexandrii Biebl et al. 2007 is a marine member of the family
      Rhodobacteraceae in the order Rhodobacterales, which has thus far only partially
      been characterized at the genome level. The bacterium is of interest because it
      lives in close association with the toxic dinoflagellate Alexandrium lusitanicum.
      Ultrastructural analysis reveals R-bodies within the bacterial cells, which are
      primarily known from obligate endosymbionts that trigger "killing traits" in
      ciliates (Paramecium spp.). Genomic traits of L. alexandrii DFL-11(T) are in
      accordance with these findings, as they include the reb genes putatively involved
      in R-body synthesis. Analysis of the two extrachromosomal elements suggests a
      role in heavy-metal resistance and exopolysaccharide formation, respectively. The
      5,461,856 bp long genome with its 5,071 protein-coding and 73 RNA genes consists
      of one chromosome and two plasmids, and has been sequenced in the context of the
      Marine Microbial Initiative. 

PMID- 24019991
TI  - Genome of the marine alphaproteobacterium Hoeflea phototrophica type strain (DFL
      43(T)).
AB  - Hoeflea phototrophica Biebl et al. 2006 is a member of the family
      Phyllobacteriaceae in the order Rhizobiales, which is thus far only partially
      characterized at the genome level. This marine bacterium contains the
      photosynthesis reaction-center genes pufL and pufM and is of interest because it
      lives in close association with toxic dinoflagellates such as Prorocentrum lima.
      The 4,467,792 bp genome (permanent draft sequence) with its 4,296 protein-coding
      and 69 RNA genes is a part of the Marine Microbial Initiative. 

PMID- 24019990
TI  - Non contiguous-finished genome sequence and description of Alistipes obesi sp.
      nov.
AB  - Alistipes obesi sp. nov. strain ph8(T) is the type strain of A. obesi, a new
      species within the genus Alistipes. This strain, whose genome is described here,
      was isolated from the fecal flora of a 26-year-old woman suffering from morbid
      obesity. A. obesi is an obligately anaerobic rod. Here we describe the features
      of this organism, together with the complete genome sequence and annotation. The
      3,162,233 bp long genome (1 chromosome but no plasmid) contains 2,623 protein
      coding and 49 RNA genes, including three rRNA genes. 

PMID- 24019992
TI  - Thermus oshimai JL-2 and T. thermophilus JL-18 genome analysis illuminates
      pathways for carbon, nitrogen, and sulfur cycling.
AB  - The complete genomes of Thermus oshimai JL-2 and T. thermophilus JL-18 each
      consist of a circular chromosome, 2.07 Mb and 1.9 Mb, respectively, and two
      plasmids ranging from 0.27 Mb to 57.2 kb. Comparison of the T. thermophilus JL-18
      chromosome with those from other strains of T. thermophilus revealed a high
      degree of synteny, whereas the megaplasmids from the same strains were highly
      plastic. The T. oshimai JL-2 chromosome and megaplasmids shared little or no
      synteny with other sequenced Thermus strains. Phylogenomic analyses using a
      concatenated set of conserved proteins confirmed the phylogenetic and taxonomic
      assignments based on 16S rRNA phylogenetics. Both chromosomes encode a complete
      glycolysis, tricarboxylic acid (TCA) cycle, and pentose phosphate pathway plus
      glucosidases, glycosidases, proteases, and peptidases, highlighting highly
      versatile heterotrophic capabilities. Megaplasmids of both strains contained a
      gene cluster encoding enzymes predicted to catalyze the sequential reduction of
      nitrate to nitrous oxide; however, the nitrous oxide reductase required for the
      terminal step in denitrification was absent, consistent with their incomplete
      denitrification phenotypes. A sox gene cluster was identified in both
      chromosomes, suggesting a mode of chemolithotrophy. In addition, nrf and psr gene
      clusters in T. oshmai JL-2 suggest respiratory nitrite ammonification and
      polysulfide reduction as possible modes of anaerobic respiration. 

PMID- 24019994
TI  - The Genomic Blueprint of Salmonella enterica subspecies enterica serovar Typhi P
      stx-12.
AB  - Salmonella enterica subspecies enterica serovar Typhi is a rod-shaped, Gram
      negative, facultatively anaerobic bacterium. It belongs to the family
      Enterobacteriaceae in the class Gammaproteobacteria, and has the capability of
      residing in the human gallbladder by forming a biofilm and hence causing the
      person to become a typhoid carrier. Here we present the complete genome of
      Salmonella enterica subspecies enterica serotype Typhi strain P-stx-12, which was
      isolated from a chronic carrier in Varanasi, India. The complete genome comprises
      a 4,768,352 bp chromosome with a total of 98 RNA genes, 4,691 protein-coding
      genes and a 181,431 bp plasmid. Genome analysis revealed that the organism is
      closely related to Salmonella enterica serovar Typhi strain Ty2 and Salmonella
      enterica serovar Typhi strain CT18, although their genome structure is slightly
      different. 

PMID- 24019995
TI  - Challenges and Needs of Chinese and Korean American Breast Cancer Survivors: In
      Depth Interviews.
AB  - Breast cancer incidence and the number of breast cancer survivors have been
      rapidly increasing among Chinese and Korean women in the United States. However,
      few data are available regarding quality of life in Asian American breast cancer
      survivors. This qualitative study aims to describe Asian American women's
      perceptions of quality of life and their breast cancer experiences. In-depth
      interviews with four Chinese and five Korean American breast cancer survivors and
      three oncologists were conducted in Chinese, Korean, or English. Interviews were
      recorded and transcripts were translated into English. Qualitative analyses were
      performed by two independent coders and then discussed and agreed upon by the
      research team. The respondents reported that the breast cancer experience had
      affected various domains of quality of life, but women reported having limited
      resources with which to cope effectively. Depression, anxiety, and stress were
      commonly reported, but women rarely discussed these issues with family and
      friends or sought professional help. As immigrants, women's loneliness and a lack
      of social support and culturally relevant resources seemed to be major barriers
      to maintaining good quality of life. Women also expressed interest in learning
      more about alternative therapies and relaxation skills. These findings can be
      used to help inform the development of a culturally appropriate intervention for
      Asian American breast cancer survivors. Future programs may provide information
      in women's native languages to teach skills to cope with stress and anxiety,
      increase women's self-efficacy within the context of their cultural background,
      and enhance social support among women from the same ethnic group.

PMID- 24019993
TI  - Complete genome sequence of Nitrosomonas sp. Is79, an ammonia oxidizing bacterium
      adapted to low ammonium concentrations.
AB  - Nitrosomonas sp. Is79 is a chemolithoautotrophic ammonia-oxidizing bacterium that
      belongs to the family Nitrosomonadaceae within the phylum Proteobacteria. Ammonia
      oxidation is the first step of nitrification, an important process in the global
      nitrogen cycle ultimately resulting in the production of nitrate. Nitrosomonas
      sp. Is79 is an ammonia oxidizer of high interest because it is adapted to low
      ammonium and can be found in freshwater environments around the world. The
      3,783,444-bp chromosome with a total of 3,553 protein coding genes and 44 RNA
      genes was sequenced by the DOE-Joint Genome Institute Program CSP 2006. 

PMID- 24019996
TI  - Monographs editor.

PMID- 24019997
TI  - Sirtuins, tissue maintenance, and tumorigenesis.
AB  - Aging is a degenerative process resulting in compromised tissue maintenance and
      increased susceptibility to diseases, such as cancer. Recent advancements support
      the notion that aging is a highly regulated process governed by evolutionarily
      conserved pathways. In mammals, tissue-specific adult stem cells (ASCs) persist
      throughout the lifetime to maintain and repair tissues. While reduced ASC self
      renewal is thought to contribute to compromised tissue maintenance, increased
      self-renewal of cancer stem cells (CSCs) may lead to tumorigenesis. It is
      speculated that genetic regulators of aging, such as sirtuins, are likely to
      impinge upon the ASC compartments to regulate tissue maintenance and
      tumorigenesis. In this review, we discuss the emerging evidence linking sirtuins
      to normal and malignant ASC self-renewal, tissue maintenance, and tumorigenesis. 

PMID- 24019998
TI  - Emerging Roles of SIRT1 in Cancer Drug Resistance.
AB  - Innate resistance to various therapeutic interventions is a hallmark of cancer.
      In recent years, acquired resistance has emerged as a daunting challenge to
      targeted cancer therapy, which abolishes the efficacy of otherwise successful
      targeting drugs. Cancer cells gain the resistance property through a variety of
      mechanisms in primary and metastatic cancers, involving cellular intrinsic and
      extrinsic factors. Increasing evidence suggests that the mammalian stress
      response gene sirtuin 1 (SIRT1) plays a critical role in multiple aspects of
      cancer drug resistance. SIRT1 decreases drug penetration, confers proliferation
      and antiapoptotic survival advantages to cancer cells, facilitates acquired
      resistance through genetic mutations, promotes the survival of cancer stem cells,
      and changes the tumor microenvironment for resistance in cell-autonomous and 
      nonautonomous manners. This article provides an overview of research advances in
      the roles of SIRT1 in cancer drug resistance and highlights the prospect of
      targeting SIRT1 as a new strategy to overcome cancer drug resistance and improve
      therapeutic outcomes. 

PMID- 24019999
TI  - Mitochondrial sirtuins as therapeutic targets for age-related disorders.
AB  - Sirtuins are a class of histone deacetylases that have a wide range of regulatory
      roles in the cell. Three sirtuins, SIRT3 to SIRT5, localize to and function
      within the mitochondria. Mitochondrial dysfunction is thought to be the
      underlying mechanism of several age-related diseases, such as metabolic syndrome,
      cancer, and neurodegeneration. This review examines current evidence that
      mitochondrial sirtuins are involved in regulating mitochondrial function and
      pathogenesis. 

PMID- 24020001
TI  - Role of sirtuins in stem cell differentiation.
AB  - Sirtuins play an essential role in the cellular response to environmental stress,
      promoting DNA repair, telomere stability, cell cycle arrest, cellular senescence,
      and apoptosis. Much attention has been given to the role of sirtuins in aging and
      cancer development; however, less is known about their role in stem cell
      regulation. This review focuses in this topic and discusses the possible
      implications in adult stem cell aging. 

PMID- 24020000
TI  - The Roles of SIRT1 in Cancer.
AB  - The sirtuin family has emerged as important regulators of diverse physiological
      and pathological events, including life-span extension, neurodegeneration, age
      related disorders, obesity, heart disease, inflammation, and cancer. In mammals,
      there are 7 members (SIRT1-SIRT7) in the sirtuin family, with the function of
      SIRT1 being extensively studied in the past decade. SIRT1 can deacetylate
      histones and a number of nonhistone substrates, which are involved in multiple
      signaling pathways. Numerous studies have suggested that SIRT1 could act as
      either a tumor suppressor or tumor promoter depending on its targets in specific
      signaling pathways or in specific cancers. This review highlights the major
      pathways regulated by SIRT1 involved in tumorigenesis. 

PMID- 24020002
TI  - SIRT1: Regulator of p53 Deacetylation.
AB  - The cellular NAD(+)/NADH level controls Sir2 (silent information regulator 2)
      deacetylase activity in regulating aging in lower species. Much work has been put
      forth to identify ways to activate SIRT1, the mammalian ortholog of Sir2. The
      identification of p53 as a bona fide substrate of SIRT1 deacetylation has linked
      SIRT1 to a role in tumorigenesis. Here, we review the various SIRT1 endogenous
      and small molecular activators and inhibitors that regulate p53 acetylation and
      subsequent activation of p53 tumor suppression activity. 

PMID- 24020003
TI  - SIRT3: A Central Regulator of Mitochondrial Adaptation in Health and Disease.
AB  - SIRT3 is a NAD(+)-dependent deacetylase that regulates the function of numerous
      mitochondrial proteins with roles in metabolism, oxidative stress, and cell
      survival. It is emerging as an instrumental regulator of the mitochondrial
      adaptive responses to stress, including metabolic reprogramming and enhancing
      antioxidant defense mechanisms. Here, we discuss the role that SIRT3 plays at
      both a cellular and physiological level and consider its involvement in disease.
      Mitochondrial dysfunction is a key contributing factor in many diseases; however,
      the mechanisms involved are often not well understood, and few targeted therapies
      exist. If manipulation of SIRT3 proves to be beneficial in disease states, then
      it could be a promising target for novel therapies. 

PMID- 24020004
TI  - SIRT1 is a Highly Networked Protein That Mediates the Adaptation to Chronic
      Physiological Stress.
AB  - SIRT1 is a NAD(+)-dependent protein deacetylase that has a very large number of
      established protein substrates and an equally impressive list of biological
      functions thought to be regulated by its activity. Perhaps as notable is the
      remarkable number of points of conflict concerning the role of SIRT1 in
      biological processes. For example, evidence exists suggesting that SIRT1 is a
      tumor suppressor, is an oncogene, or has no effect on oncogenesis. Similarly,
      SIRT1 is variably reported to induce, inhibit, or have no effect on autophagy. We
      believe that the resolution of many conflicting results is possible by
      considering recent reports indicating that SIRT1 is an important hub interacting
      with a complex network of proteins that collectively regulate a wide variety of
      biological processes including cancer and autophagy. A number of the interacting
      proteins are themselves hubs that, like SIRT1, utilize intrinsically disordered
      regions for their promiscuous interactions. Many studies investigating SIRT1
      function have been carried out on cell lines carrying undetermined numbers of
      alterations to the proteins comprising the SIRT1 network or on inbred mouse
      strains carrying fixed mutations affecting some of these proteins. Thus, the
      effects of modulating SIRT1 amount and/or activity are importantly determined by
      the genetic background of the cell (or the inbred strain of mice), and the
      effects attributed to SIRT1 are synthetic with the background of mutations and
      epigenetic differences between cells and organisms. Work on mice carrying
      alterations to the Sirt1 gene suggests that the network in which SIRT1 functions
      plays an important role in mediating physiological adaptation to various sources
      of chronic stress such as calorie restriction and calorie overload. Whether the
      catalytic activity of SIRT1 and the nuclear concentration of the co-factor,
      NAD(+), are responsible for modulating this activity remains to be determined.
      However, the effect of modulating SIRT1 activity must be interpreted in the
      context of the cell or tissue under investigation. Indeed, for SIRT1, we argue
      that context is everything. 

PMID- 24020005
TI  - Deacetylation by SIRT1 Reprograms Inflammation and Cancer.
AB  - NAD(+)-dependent deacetylase SIRT1 is a master regulator of nucleosome
      positioning and chromatin structure, thereby reprogramming gene expression. In
      acute inflammation, chromatin departs from, and returns to, homeostasis in an
      orderly sequence. This sequence depends on shifts in NAD(+) availability for
      SIRT1 activation and deacetylation of signaling proteins, which support orderly
      gene reprogramming during acute inflammation by switching between euchromatin and
      heterochromatin. In contrast, in chronic inflammation and cancer, limited
      availability of NAD(+) and reduced expression of SIRT1 may sustain aberrant
      chromatin structure and functions. SIRT1 also influences inflammation and cancer
      by directly deacetylating targets like NFkappaB p65 and p53. Here, we review
      SIRT1 in the context of inflammation and cancer. 

PMID- 24020006
TI  - The diversity of histone versus nonhistone sirtuin substrates.
AB  - The members of the Sir2 family, or sirtuins, are major regulators of the response
      to different types of stress. The members of the family have adapted to
      increasing complexities throughout evolution and have become diversified by
      increasing their number, specificity, and localization and acquiring novel
      functions. Sirtuins have been consistently implicated in the cross-talk between
      the genomic information and environment from the prokaryotes onward. Evidence
      suggests that in the transition to eukaryotes, histones became one of the basic
      and most conserved targets of the family, to the extent that in yeast and
      mammals, sirtuins were originally described as NAD(+)-dependent histone
      deacetylases and classified as class III histone deacetylases. A growing number
      of studies have determined that sirtuins also target a wide range of nonhistone
      proteins. Many of these targets are also directly or indirectly related to
      chromatin regulation. The number of targets has grown considerably in the last
      decade but has provoked an ill-founded discussion that neglects the importance of
      histones as sirtuin targets. In this review, we summarize our knowledge regarding
      the range of sirtuin targets described to date and discuss the different
      functional implications of histone and nonhistone targets throughout evolution. 

PMID- 24020007
TI  - Sirtuin-3 (SIRT3) and the Hallmarks of Cancer.
AB  - Sirtuins (SIRT1-SIRT7), the mammalian homologs of the silent information
      regulator 2 (Sir2) in Saccharomyces cerevisiae, have been a major focus of study
      in the scientific community this past decade because of their emerging role in
      cancer biology and other age-related diseases. Emerging functions for this unique
      family of enzymes include roles in genomic stability, angiogenesis, metabolism,
      and anoikis. Here, we review recent developments on the role of sirtuins in
      cancer with a particular focus on SIRT3 and its role in the hallmarks of cancer
      and as a potential drug target for cancer treatment. 

PMID- 24020009
TI  - Concentric energy transfer with quantum dots for multiplexed biosensing.

PMID- 24020008
TI  - Stress Inducibility of SIRT1 and Its Role in Cytoprotection and Cancer.
AB  - Cells must continuously respond to stressful insults via the upregulation of
      cytoprotective pathways. The longevity factor and deacetylase SIRT1 plays a
      critical role in coordinating this cellular response to stress. SIRT1 activity
      and levels are regulated by cellular stressors, including metabolic, genotoxic,
      oxidative, and proteotoxic stress. As a stress sensor, SIRT1 impacts cell
      survival by deacetylating substrate proteins to drive the cell towards a
      cytoprotective pathway. Extreme stress conditions, however, can cause SIRT1 to
      lead cells down an apoptotic pathway instead. SIRT1 is frequently dysregulated in
      cancer cells and has been characterized to have a dual role as both an oncogene
      and a tumor suppressor, likely due to its pivotal function in regulating
      cytoprotection. Recently, the ability of SIRT1 to regulate HSF1-dependent
      induction of the heat shock response has highlighted another pathway through
      which SIRT1 can modulate cytoprotection. Activation of HSF1 results in the
      production of cytoprotective chaperones that can facilitate the transformed
      phenotype of cancer cells. In this review, we discuss the stress-dependent
      regulation of SIRT1. We highlight the role of SIRT1 in stress management and
      cytoprotection and emphasize SIRT1-dependent activation of HSF1 as a potential
      mechanism for cancer promotion. 

PMID- 24020010
TI  - Dysregulation in cortical reactivity to emotional faces in PTSD patients with
      high dissociation symptoms.
AB  - BACKGROUND: Predominant dissociation in posttraumatic stress disorder (PTSD) is
      characterized by restricted affective responses to positive stimuli. To date, no
      studies have examined neural responses to a range of emotional expressions in
      PTSD with high dissociative symptoms. OBJECTIVE: This study tested the hypothesis
      that PTSD patients with high dissociative symptoms will display increased event
      related potential (ERP) amplitudes in early components (N1, P1) to threatening
      faces (angry, fearful), and reduced later ERP amplitudes (Vertex Positive
      Potential (VPP), P3) to happy faces compared to PTSD patients with low
      dissociative symptoms. METHODS: Thirty-nine civilians with PTSD were classified
      as high dissociative (n=16) or low dissociative (n=23) according to their
      responses on the Clinician Administered Dissociative States Scale. ERPs were
      recorded, whilst participants viewed emotional (happy, angry, fear) and neutral
      facial expressions in a passive viewing task. RESULTS: High dissociative PTSD
      patients displayed significantly increased N120 amplitude to the majority of
      facial expressions (neutral, happy, and angry) compared to low dissociative PTSD
      patients under conscious and preconscious conditions. The high dissociative PTSD
      group had significantly reduced VPP amplitude to happy faces in the conscious
      condition. CONCLUSION: High dissociative PTSD patients displayed increased early
      (preconscious) cortical responses to emotional stimuli, and specific reductions
      to happy facial expressions in later (conscious), face-specific components
      compared to low dissociative PTSD patients. Dissociation in PTSD may act to
      increase initial pre-attentive processing of affective stimuli, and specifically
      reduce cortical reactivity to happy faces when consciously processing these
      stimuli.

PMID- 24020011
TI  - Chronic ulcers: MATRIDERM((r)) system in smoker, cardiopathic, and diabetic
      patients.
AB  - Diabetic ulcers and pressure ulcers represent a more frequent cause of chronic
      wounds in aging populations. It is estimated that approximately 15% of the
      diabetic population will develop diabetic ulcers during their life and over half
      of these patients develop an infection, often osteomyelitis, with 20% requiring
      amputation. The authors report a case of a 65-year-old woman affected by a post
      traumatic loss of substance due to road accidents with soft tissue exposure
      (comprising muscle tendon) of the left knee combined with the fracture of the
      right fibula previously subjected to surgery and reconstruction of muscle tendon.
      The patient was affected by diabetes type II, hypertension, and ischemic heart
      disease. In 2008, she underwent a double bypass surgery and coronary angioplasty.
      Initially, the patient was treated with cycles of advanced dressings, with
      fibrinolytic ointments, hydrocolloid, and subsequently, when the bottom began
      granulated with fibrinolytic and idrocellulosa, Hydrofibra-Ag, and Ag-alginate,
      three times a week for 30 days. In the second step, the authors decided to treat
      the ulcer with the MATRIDERM system and auto skin graft. Following the first
      treatment, 7 days after the procedure, the authors found the reduction of the
      loss of substance until its complete closure. The wound's infection was evaluated
      by a buffer negative confirmation performed every 2 weeks four times. We obtained
      decrease of limb edema and full functional rehabilitation. The skin appeared
      renovated, with volume restoration and an improvement of the texture. 

PMID- 24020012
TI  - Silica-based mesoporous nanoparticles for controlled drug delivery.
AB  - Drug molecules with lack of specificity and solubility lead patients to take high
      doses of the drug to achieve sufficient therapeutic effects. This is a leading
      cause of adverse drug reactions, particularly for drugs with narrow therapeutic
      window or cytotoxic chemotherapeutics. To address these problems, there are
      various functional biocompatible drug carriers available in the market, which can
      deliver therapeutic agents to the target site in a controlled manner. Among the
      carriers developed thus far, mesoporous materials emerged as a promising
      candidate that can deliver a variety of drug molecules in a controllable and
      sustainable manner. In particular, mesoporous silica nanoparticles are widely
      used as a delivery reagent because silica possesses favourable chemical
      properties, thermal stability and biocompatibility. Currently, sol-gel-derived
      mesoporous silica nanoparticles in soft conditions are of main interest due to
      simplicity in production and modification and the capacity to maintain function
      of bioactive agents. The unique mesoporous structure of silica facilitates
      effective loading of drugs and their subsequent controlled release. The
      properties of mesopores, including pore size and porosity as well as the surface
      properties, can be altered depending on additives used to fabricate mesoporous
      silica nanoparticles. Active surface enables functionalisation to modify surface
      properties and link therapeutic molecules. The tuneable mesopore structure and
      modifiable surface of mesoporous silica nanoparticle allow incorporation of
      various classes of drug molecules and controlled delivery to the target sites.
      This review aims to present the state of knowledge of currently available drug
      delivery system and identify properties of an ideal drug carrier for specific
      application, focusing on mesoporous silica nanoparticles. 

PMID- 24020013
TI  - Six years of clinical follow-up with endothelial cell-seeded small-diameter
      vascular grafts during coronary bypass surgery.
AB  - This clinical study was performed to investigate the patency rate of endothelial
      cell-seeded small-diameter expanded polytetrafluoroethylene grafts during
      coronary artery bypass surgery. Between September 1995 and December 1998, 14
      patients (median age: 71 years, range: 61-79 years) received 21 endothelial cell
      seeded small-diameter grafts. In all, 43% of the performed implantations were
      reoperations. Endothelial cells were harvested from a forearm vein, cultured and
      characterized in the laboratory until a sufficient number was available. After in
      vitro seeding, the grafts were allowed to mature for another 10 days, prior to
      implantation. Graft patency was investigated with angiography, angioscopy, and
      intravascular ultrasonography during follow-up. Cumulative data represented 58
      patients' years and was 100% complete. The seeded autologous vascular endothelial
      cell density was 1.05 * 10(5) +/- 0.12 * 10(5) cells/cm(2) with a cell viability
      of 95.5 +/- 1.5%. Operative mortality was 7.1% (one patient). Patency rate at
      discharge was 95.2%, and at a mean follow-up of 27 months was 90.5%. The proven
      patency rate at up to 72 months was at least 50.0%, as five patients refused
      angiographic evaluation. None of these five patients suffered from angina
      pectoris and so the best scenario would have shown a patency rate of 85.7%.
      Angioscopy and intravascular ultrasonography showed absence of atheroma or
      stenosis in the investigated patent grafts. Autologous vascular endothelial cell
      seeding improves patency rate of small-caliber expanded polytetrafluoroethylene
      grafts in patients without suitable autologous graft material. 

PMID- 24020017
TI  - Malignant thyroid bed mass after total thyroidectomy.
AB  - PURPOSE: Ultrasonographic (US) criteria on malignant thyroid bed mass have been
      suggested, including taller than wide shape, loss of echogenic hilum, abnormal
      vascularity, and microcalcification. The relationship between fine-needle
      aspiration (FNA) cytology findings and US findings on thyroid bed mass is
      unknown. We have retrospectively assessed the malignant thyroid bed mass after
      total thyroidectomy due to papillary thyroid carcinoma (PTC). METHODS: We
      retrospectively evaluated 2,048 patients who underwent total thyroidectomy due to
      PTC. FNA was performed in 97 patients on the thyroid bed under US surveillance.
      The 97 suspicious thyroid bed masses were divided into two groups: metastatic
      thyroid bed group (n = 34) and nonmetastatic group (n = 63). The groups were
      evaluated according to various clinical, serologic, and US findings. RESULTS:
      Within a median 47.0 months of follow-up, the proportion of malignant thyroid bed
      mass was high in large tumor size (1.37 cm vs. 1.03 cm), isthmic position (10.3%
      vs. 3.9%), and previous N1a (55.9% vs. 34.9%). US findings revealed that the
      presence of microcalcification or macrocalcification (47.1% vs. 19.0%) and
      thyroid bed mass height (5.4 mm vs. 3.9 mm) were the only discriminable criteria
      for central compartment recurrence. But, degree of echogenicity, loss of hilum,
      and irregularity of margin failed to discriminate malignant thyroid bed mass.
      CONCLUSION: US findings on malignant thyroid bed mass were different from
      previously reported general criteria on lateral metastatic nodes. Additional FNA
      cytology should be performed on patients, even low-risk patients, who present the
      above findings.

PMID- 24020018
TI  - On-site ultrasound-guided localization for impalpable nodal recurrences in
      papillary thyroid carcinoma patients.
AB  - PURPOSE: The cervical lymph nodes are the most common sites of locoregional
      recurrence in patients with papillary thyroid carcinoma (PTC). Accurate tumor
      localization is important for the successful removal of impalpable recurrences in
      the cervical lymph nodes. We evaluated the benefits of ultrasound-guided
      localization (UGL) performed by a single surgeon on site. METHODS: Of 53 PTC
      patients who underwent reoperation for impalpable nodal recurrences, 32 (group 1)
      were assessed only using preoperative imaging, while 21 (group 2) were
      additionally evaluated by on-site UGL performed by the operating surgeon.
      Postoperative outcomes were compared between the two groups. RESULTS: Operation
      times were significantly shorter (P < 0.001) and the mean size of the resected
      lymph nodes were smaller (P = 0.013) for group 2 patients. More lymph nodes were
      identified and resected in group 1 (3.56 vs. 3.19), but the rate of positive
      lymph nodes was significantly higher in group 2 (P < 0.001). There were no
      differences between the two groups in terms of resection success rate,
      complication rate, and postoperative hospital stay. During a mean follow-up
      period of 27.6 months, 52 patients (98.1%) showed no evidence of recurrence on
      routine ultrasound, and serum thyroglobulin concentrations remained < 1 ng/mL in
      49 patients (92.5%). CONCLUSION: On-site UGL performed by the operating surgeon
      is useful for accurate resection of impalpable nodal recurrences in PTC patients.

PMID- 24020014
TI  - Pharmacogenetic testing: Current Evidence of Clinical Utility.
AB  - Over the last decade, the number of clinical pharmacogenetic tests has steadily
      increased as understanding of the role of genes in drug response has grown.
      However, uptake of these tests has been slow, due in large part to the lack of
      robust evidence demonstrating clinical utility. We review the evidence behind
      four pharmacogenetic tests and discuss the barriers and facilitators to uptake:
      1) warfarin (drug safety and efficacy); 2) clopidogrel (drug efficacy); 3)
      codeine (drug efficacy); and 4) abacavir (drug safety). Future efforts should be
      directed toward addressing these issues and considering additional approaches to
      generating evidence basis to support clinical use of pharmacogenetic tests.

PMID- 24020019
TI  - The effect of duodenojejunal bypass for type 2 diabetes mellitus patients below
      body mass index 25 kg/m(2): one year follow-up.
AB  - PURPOSE: The goals of this study are to evaluate the effect of duodenojejunal
      bypass (DJB) for type 2 diabetes mellitus (T2DM) patients below body mass index
      (BMI) 25 kg/m(2) in one year follow-up, and to compare the results of 1 week
      which we have reported in 2011. METHODS: In this prospective observational study,
      there were 31 type 2 diabetic patients who underwent DJB at Inha University
      Hospital from July 2009 to January 2011. We did laboratories such as 75-g oral
      glucose tolerance test (OGTT), insulin level and hemoglobin A1c (HbA1c), etc. and
      compared their changes of preoperative, a week, 3 months, and 12 months. RESULTS:
      Mean BMI was 23.1 +/- 1.3 kg/m(2), mean duration of T2DM was 8.3 +/- 4.7 and mean
      age was 46.6 +/- 7.7 years. There were a significant decrease of 75-g OGTT levels
      and increase of insulin secretion after 3 months. 13.3% showed diabetic remission
      (HbA1c < 6.0, medication cessation) and 26.7% showed diabetic improvement. The
      rates of remission and improvement much declined comparing with that of
      postoperative 1 week although those were determined by fasting and postprandial 2
      hour level of glucose. CONCLUSION: This is the first study of metabolic surgery
      in Korean diabetes patients in the healthy weight range. DJB exerted positive
      influences on insulin resistance as well as beta cell function. Early effects on
      T2DM after DJB could be estimated as one of good modalities, although the
      effectiveness seems to be unacceptable. Further studies are mandatory for
      evaluation of the effectiveness of metabolic surgery and finding prognostic
      factors.

PMID- 24020020
TI  - Management of giant hepatic cysts in the laparoscopic era.
AB  - PURPOSE: We sought to evaluate the feasibility and outcomes of laparoscopic
      resection of giant hepatic cysts and surgical success, focusing on cyst
      recurrence. METHODS: From February 2004 to August 2011, 37 consecutive patients
      with symptomatic hepatic cysts were evaluated and treated at Dong-A University
      Hospital. Indications were simple cysts (n = 20), multiple cysts (n = 6),
      polycystic disease (n = 2), and cystadenoma (n = 9). RESULTS: The median patient
      age was 64 years, with a mean lesion diameter of 11.4 cm. The coincidence between
      preoperative imaging and final pathologic diagnosis was 54% and half (n = 19) of
      the cysts were located in segments VII and VIII. Twenty-two patients had American
      Society of Anesthesiologists (ASA) classification I and II, and nine had ASA
      classification III. Surgical treatment of hepatic cysts were open liver resection
      (n = 3), laparoscopic deroofing (n = 24), laparoscopic cyst excision (n = 4),
      laparoscopic left lateral sectionectomy (n = 2), hand assisted laparoscopic
      procedure (n = 2), and single port laparoscopic deroofing (n = 2). The mean
      fellow-up was 21 months, and six patients (16%) experienced radiographic-apparent
      recurrence. Reoperation due to recurrence was performed in two patients. Among
      the factors predicting recurrence, multivariate analysis revealed that
      interventional radiological procedures and pathologic diagnosis were
      statistically significant. CONCLUSION: Laparoscopic resection of giant hepatic
      cysts is a simple and effective method to relieve symptoms with minimal surgical
      trauma. Moreover, the recurrence is dependent on the type of pathology involved,
      and the sclerotherapy undertaken.

PMID- 24020021
TI  - The role of hand-assisted laparoscopic surgery in total colectomy for colonic
      inertia: a retrospective study.
AB  - PURPOSE: To compare and assess the efficacy, safety and utility of hand-assisted
      laparoscopic surgery (HALS) with open surgery (OS) in total colectomy with
      ileorectal for colonic inertia. METHODS: From January 2001 to February 2012, 56
      patients diagnosed with colonic inertia who failed to respond to medical
      treatments underwent hand-assisted laparoscopic total colectomy with ileorectal
      anastomosis. Another 68 patients underwent laparotomy. Main parameters such as
      clinical manifestations, conversion to open procedure, operative time, incision
      length, pain score, intraoperative blood loss, time to first flatus and
      hospitalization, early postoperative complications and hospitalization cost were
      retrospectively analyzed. Postoperative defecating frequencies were followed up
      in both groups. RESULTS: All patients received successful operation, no surgical
      mortality happened and none of the patients required conversion to an exploratory
      laparotomy in HALS group. The clinical features, the estimated blood loss,
      incision length, pain score, first passing flatus time, and postoperative
      hospitalization time were superior in HALS group (P < 0.05). The early
      postoperative complications and frequency of defecation were similar. However,
      the mean operative time was longer and hospitalization cost was higher in HALS
      group than those in OS group (P < 0.05). CONCLUSION: HALS total colectomy can be
      a safe and efficient technique in the treatment of colonic inertia. HALS can
      result in a better cosmetic result and a quicker postoperative recovery, but
      requires higher direct cost.

PMID- 24020022
TI  - Postoperative analgesic effects of ultrasound-guided transversus abdominis plane
      block for open appendectomy.
AB  - PURPOSE: Transversus abdominis plane (TAP) block is a newly developed and
      effective peripheral block involving the nerves of the anterior abdominal wall
      for lower abdominal surgery. We evaluated the postoperative analgesic efficacy of
      ultrasound-guided TAP block using 20 mL of 0.5% levobupivacaine in patients
      undergoing open appendectomy. METHODS: Forty-four patients undergoing
      appendectomy were assigned either to undergo a right sided-TAP block (group I, n
      = 22), or to receive standard care (group II, n = 22). All patients received
      standard anesthetics, and the TAP block group received ultrasound-guided right
      side TAP block using 20 mL of 0.5% levobupivacaine after induction of anesthesia.
      All patients received acetaminophen, and nonsteroidal anti-inflammatory drug as
      required during the 48 postoperative hours. Each patients was assessed for time
      to first rescue analgesia, verbal numerical rating pain scores (VNRS), number of
      rescue analgesic demands, nausea, vomiting, pruritus, and drowsiness by a blinded
      investigator at 0, 1, 3, 6, 12, 24 and 48 hours postoperatively. RESULTS: The TAP
      block group with levobupivacaine compared to the control group reduced VNRS
      significantly up to 12 hours postoperatively. There were no significant
      differences in time to first analgesia, number of rescue analgesics demands,
      nausea, vomiting, pruritus and drowsiness between the groups. There were no
      complications attributable to the TAP block. CONCLUSION: Ultrasound-guided TAP
      block using 20 mL of 0.5% levobupivacaine provided effective postoperative
      analgesia during the 12 postoperative hours after an open appendectomy.

PMID- 24020024
TI  - Pinch-off syndrome.
AB  - Subclavian venous catheterization was previously frequently performed, but
      because of life-threatening complications such as hemothorax, pneumothorax,
      mediastinal hematoma, and myocardial injury, its use has become less common.
      However, this practice has some advantages in patient mobility, secured dressing,
      and rapidity and adequacy of vascular access. In some situations where patient
      comfort is an especially important consideration, such as with totally
      implantable venous port insertion for chemotherapy, the subclavian route can be a
      good choice if an experienced and well-trained faculty is available. The authors
      have had recent experience with pinch-off syndrome-in other words, spontaneous
      catheter fracture-in 3 patients who had undergone venous port implantation
      through the right subclavian route. Through these cases, we intend to review the
      dangers of subclavian venous catheterization, the causes of pinch-off syndrome,
      and its clinical presentation, progress, treatments, and prevention. 

PMID- 24020023
TI  - Negative pressure wound therapy for inguinal lymphatic complications in
      critically ill patients.
AB  - PURPOSE: In this study, we investigated the therapeutic potential of regulated
      negative pressure vacuum-assisted wound therapy for inguinal lymphatic
      complications in critically ill, liver transplant recipients. METHODS: The great
      saphenous vein was harvested for hepatic vein reconstruction during liver
      transplantation in 599 living-donor liver transplant recipients. Fourteen of the
      recipients (2.3%) developed postoperative inguinal lymphatic complications and
      were treated with negative pressure wound therapy, and they were included in this
      study. RESULTS: The average total duration of negative pressure wound therapy was
      23 days (range, 11 to 42 days). Complete resolution of the lymphatic
      complications and wound healing were achieved in all 14 patients, 5 of whom were
      treated in hospital and 9 as outpatients. There was no clinically detectable
      infection, bleeding or recurrence after an average follow-up of 27 months (range,
      7 to 36 months). CONCLUSION: Negative pressure wound therapy is an effective,
      readily-available treatment option that is less invasive than exploration and
      ligation of leaking lymphatics and provides good control of drainage and rapid
      wound closure in critically ill patients.

PMID- 24020025
TI  - Endovascular repair of bilateral iliac artery aneurysm with branched iliac
      stents: case report and review of the current literature.
AB  - Common iliac artery aneurysm (CIA) often occurs in conjunction with an abdominal
      aortic aneurysm (AAA), which extends into one or both CIAs in 20% to 30% of
      patients. Conventional endovascular treatment includes coil embolization of the
      internal iliac artery (IIA), followed by extension of the main bifurcated AAA
      stent-graft into the external iliac artery. However, complications from
      intentional occlusion of unilateral or bilateral IIAs are frequent and sometimes
      serious. Several methods try to preserve the unilateral or bilateral IIA. Here we
      report a case of concomitant bilateral CIA and AAA successfully treated with
      bilateral branched iliac stent-grafts. 

PMID- 24020026
TI  - The effect of extracorporeal shock wave therapy on lower limb spasticity in
      subacute stroke patients.
AB  - OBJECTIVE: To evaluate the effect of extracorporeal shock wave therapy (ESWT) on
      lower limb spasticity in subacute stroke patients. METHODS: We studied thirty
      hemiplegic subacute stroke patients with ankle plantar flexor spasticity. ESWT
      was applied for 1 session/week, with a total of 3 sessions at the
      musculotendinous junction of medial and lateral gastrocnemius muscles. Patients
      were evaluated both clinically and biomechanically at baseline, after sham
      stimulation, and at immediately 1 week and 4 weeks after ESWT. For clinical
      assessment, Modified Ashworth Scale (MAS), clonus score, passive range of motion
      of ankle, and Fugl-Myer Assessment for the lower extremity were used. A
      biomechanical assessment of spasticity was conducted by an isokinetic
      dynamometer. Two parameters, peak eccentric torque (PET) and torque threshold
      angle (TTA), were analyzed at the velocities of 60 degrees /sec, 180 degrees
      /sec, and 240 degrees /sec. RESULTS: After sham stimulation, there were no
      significant changes between each assessment. MAS and PET (180 degrees /sec and
      240 degrees /sec) were significantly improved immediately and 1 week after ESWT.
      However, these changes were not significant at 4 weeks after ESWT. PET (60
      degrees /sec) and TTA (60 degrees /sec, 180 degrees /sec, and 240 degrees /sec)
      were significantly improved immediately after ESWT. Yet, these changes were not
      significant at 1 week and 4 weeks after ESWT as well. CONCLUSION: Lower limb
      spasticity in subacute stroke patients was significantly improved immediately
      after ESWT. Although the therapeutic effect of ESWT reduced with time and
      therefore was not significant at 4 weeks after ESWT, the degree of spasticity was
      lower than that of the baseline. Future studies with a larger sample of patients
      are warranted in order to verify the protocols which can optimize the effect of
      ESWT on spasticity.

PMID- 24020027
TI  - Prevalence of the rotator cuff tear increases with weakness in hemiplegic
      shoulder.
AB  - OBJECTIVE: To investigate the relationship between the rotator cuff tear (RCT)
      and the muscle strength in hemiplegic side, and the effects of paralysis on the
      affected shoulders in hemiplegic patients. METHODS: A cross-sectional
      observational study performed in a university hospital was presented. The study
      enrolled 55 participants with hemiplegia of diverse degree of motor paresis,
      excluding those with bilateral lesions, history of major trauma or other co
      existing musculoskeletal disorders of the shoulder. The main outcome measurements
      were muscle strength of the affected upper extremity (based on Medical Research
      Council scale), RCTs of the bilateral shoulders (by ultrasonography), and
      presence of shoulder pain, subluxation of the glenohumeral joint, passive range
      of motions, and subacromial spurs. RESULTS: Comparing each side of the shoulders,
      the prevalence of shoulder pain and supraspinatus muscle tear was higher
      (p<0.0001, p=0.007), and the range of motion was restricted (p<0.0001, p<0.0001,
      p<0.0001, p<0.0001) in the affected side. There was a significant trend toward
      higher prevalence of RCT and shoulder subluxation in the weaker shoulder
      (p=0.019, p<0.0001). In a multivariate analysis, Manual Muscle Test grade of less
      than three was an independent risk factor for RCT (p=0.025). CONCLUSION: RCT in
      hemiplegia had a linear trend with muscle weakness in the affected side and the
      degree of weakness was an independent risk factor for the occurrence of RCT. In
      addition, shoulder pain, limitation of range of motions, and RCT were more
      frequent on the hemiplegic side of the shoulders. It is the first study to reveal
      a linear trend between RCT and upper extremity weakness and will provide
      physicians an insight to the management of RCTs in hemiplegic patients.

PMID- 24020028
TI  - Validity and reliability of the korean version of the MD anderson Dysphagia
      inventory for head and neck cancer patients.
AB  - OBJECTIVE: To translate the MD Anderson Dysphagia Inventory (MDADI) which is a
      self-administered questionnaire that assesses effect of dysphagia on the quality
      of life for patients with head and neck cancer, into Korean and to verify the
      validity and reliability of the Korean version of MDADI. METHODS: We performed 6
      steps for the cross-cultural adaptation which consisted of translation,
      synthesis, back translation, review by an expert committee, cognitive debriefing,
      and final proof reading. A total of 34 dysphagia patients with head and neck
      cancers from Seoul National University Hospital answered the translated version
      of the questionnaire for the pre-testing. The patients answered the same
      questionnaire 2 weeks later to verify the test-retest reliability. RESULTS: One
      patient was excluded at second survey because he changed his feeding strategy.
      Overall, 33 patients completed the study. Linguistic validations were achieved by
      each step of cross-cultural adaptation. We gathered statistically strong
      construct validity (Spearman rho for subdomain scores to total score correlation
      range from 0.852 to 0.927), internal consistency for subdomains (Cronbach's alpha
      coefficients range from 0.785 to 0.889) and test-retest reliability (intra-class
      correlation coefficient range from 0.820 to 0.955). CONCLUSION: The Korean
      version of the MDADI achieved linguistic validations and demonstrated good
      construct validity and reliability. It can be a useful tool for screening and
      treatment planning for the dysphagia of patients with head and neck cancers.

PMID- 24020029
TI  - Reliability and Validity of the Korean World Health Organization Quality of Life
      (WHOQOL)-BREF in People With Physical Impairments.
AB  - OBJECTIVE: To identify the validity and reliability of the Korean version World
      Health Organization Quality of Life Assessment (WHOQOL)-BREF among people with
      physical impairments living in a community. METHODS: Participants listed in the
      community-based rehabilitation project were recruited from 45 public health
      centers. People with brain lesions or physical disabilities were selected.
      Respondents (n=750) filled out the Korean WHOQOL-BREF questionnaire. Obtained
      data were analyzed statistically to assess the internal consistency as well as
      the construct and discriminant validity. An exploratory factor analysis was also
      performed. RESULTS: Cronbach's alpha for the total score was 0.839. The value for
      each domain ranged from 0.746 to 0.849. Pearson correlation coefficient between
      each domain ranged from 0.539 to 0.717. The highest correlation was between the
      psychological and physical domain. The item-domain correlation indicated a
      significant correlation with their original domains. A multiple regression
      analysis of each domain with two overall questions was performed. The
      psychological domain made the strongest contribution with the overall quality of
      life (unstandardized coefficient B=0.065, r(2)=0.437). When general health
      satisfaction was considered as a dependent variable, the physical domain most
      strongly contributed to the variable (unstandardized coefficient B=0.081,
      r(2)=0.462). Exploratory factor analysis yielded four factors in the WHOQOL-BREF,
      accounting for 55.29% of the variability. To assess the discriminant validity, a
      comparison of each domain with Modified Barthel Index (MBI) was conducted. There
      were highly significant changes across the MBI scores with the WHOQOL-BREF
      domains (p<0.001). CONCLUSION: Korean WHOQOL-BREF is a valid and reliable tool to
      measure the quality of life for people with physical impairments. It has good
      internal consistency, construct validity and discriminant validity for the
      population. Further study with a stratified sample is needed.

PMID- 24020030
TI  - The location of multifidus atrophy in patients with a single level, unilateral
      lumbar radiculopathy.
AB  - OBJECTIVE: To identify the correlations between the location of multifidus
      atrophy and the level of lumbar radiculopathy. METHODS: Thirty-seven patients who
      had unilateral L4 or L5 radiculopathy were divided into 2 groups; the L4
      radiculopathy (L4 RAD) group and the L5 radiculopathy (L5 RAD) group. Bilateral
      lumbar multifidus muscles at the mid-spinous process level of L4 vertebra (L4
      MSP), the mid-spinous process level of L5 vertebra (L5 MSP), and the mid-sacral
      crest level of S1 vertebra (S1 MSC) were detected in T1 axial magnetic resonance
      imaging. The total muscle cross-sectional area of multifidus muscles (TMCSA) and
      the pure muscle cross-sectional area of multifidus muscles (PMCSA) were measured
      by a computerized analysis program, and the ratio of PMCSA to TMCSA (PMCSA/TMCSA)
      was calculated. RESULTS: There were no significant differences in TMCSA between
      the involved and the uninvolved sides in both groups. PMCSA was only
      significantly smaller at the S1 MSC on the involved side as compared with the
      uninvolved side in the L5 RAD group. The ratio of PMCSA to TMCSA was the lowest
      at the L5 MSP on the involved side in the L4 RAD group and at the S1 MSC on the
      involved side in the L5 RAD group. CONCLUSION: Our findings suggest that the most
      severe atrophy of multifidus muscle may occur at the mid-spinous process or mid
      sacral crest level of the vertebra which is one level below the segmental number
      of the involved nerve root in patients with a single-level, unilateral lumbar
      radiculopathy.

PMID- 24020031
TI  - Therapeutic effect of whole body vibration on chronic knee osteoarthritis.
AB  - OBJECTIVE: To investigate the effect on pain reduction and strengthening of the
      whole body vibration (WBV) in chronic knee osteoarthritis (OA). METHODS: PATIENTS
      WERE RANDOMLY DIVIDED INTO TWO GROUPS: the study group (WBV with home based
      exercise) and control group (home based exercise only). They performed exercise
      and training for 8 weeks. Eleven patients in each group completed the study. Pain
      intensity was measured with the Numeric Rating Scale (NRS), functional scales
      were measured with Korean Western Ontario McMaster score (KWOMAC) and Lysholm
      Scoring Scale (LSS), quadriceps strength was measured with isokinetic torque and
      isometric torque and dynamic balance was measured with the Biodex Stability
      System. These measurements were performed before training, at 1 month after
      training and at 2 months after training. RESULTS: NRS was significantly decreased
      in each group, and change of pain intensity was significantly larger in the study
      group than in the control group after treatment. Functional improvements in
      KWOMAC and LSS were found in both groups, but no significant differences between
      the groups after treatment. Dynamic balance, isokinetic strength of right
      quadriceps and isometric strengths of both quadriceps muscles improved in both
      groups, but no significant differences between the groups after treatment.
      Isokinetic strength of left quadriceps did not improve in both groups after
      treatment. CONCLUSION: In chronic knee OA patients, WBV reduced pain intensity
      and increased strength of the right quadriceps and dynamic balance performance.
      In comparison with the home based exercise program, WBV was superior only in pain
      reduction and similarly effective in strengthening of the quadriceps muscle and
      balance improvement.

PMID- 24020032
TI  - Effects on foot external rotation of the modified ankle-foot orthosis on post
      stroke hemiparetic gait.
AB  - OBJECTIVE: To evaluate the effects of heel-opened ankle foot orthosis (HOAFO) on
      hemiparetic gait after stroke, especially on external foot rotation, and to
      compare the effects of HOAFO with conventional plastic-AFO (pAFO) and barefoot
      during gait. METHODS: This cross-over observational study involved 15 hemiparetic
      patients with external rotation of the affected foot. All subjects were able to
      walk independently, regardless of their usual use of a single cane, and had a
      less than fair-grade in ankle dorsiflexion power. Each patient was asked to walk
      in three conditions with randomized sequences: 1) barefoot, 2) with a pAFO, and
      3) with an HOAFO. Their gait patterns were analyzed using a motion analysis
      system. RESULTS: Fifteen patients consisted of nine males and six females. On
      gait analysis, hip and foot external rotation were significantly greater in pAFO
      (-3.35 degrees  and -23.68 degrees ) than in barefoot and HOAFO conditions
      (p<0.05). Wearing an HOAFO resulted in significant decreases in hip (0.78 degrees
      , p=0.04) and foot (-17.99 degrees , p<0.01) external rotation compared with
      pAFO; although there was no significant difference between HOAFO and barefoot
      walking. Walking speed and percentage of single limb support were significantly
      greater for HOAFO than in barefoot walking. CONCLUSION: HOAFO was superior to
      pAFO in reducing hip and foot external rotation during the stance phase in
      patients with post-stroke hemiparesis. HOAFO may, therefore, be useful in
      patients with excessive external rotation of the foot during conventional pAFO.

PMID- 24020033
TI  - Changes in balancing ability of athletes with chronic ankle instability after
      foot orthotics application and rehabilitation exercises.
AB  - OBJECTIVE: To compare the effect of foot orthotics and rehabilitation exercises
      by assessing balancing ability and joint proprioception in athletes who have
      chronic ankle instability. METHODS: Forty-one athletes who visited hospitals due
      to chronic ankle instability were randomly assigned to two groups. One group had
      ankle rehabilitation exercises while the other group had the same rehabilitation
      exercises as well as foot orthotics. Joint position sense of the ankle joint was
      examined by using an isokinetic exercise machine. Balancing abilities categorized
      into static, dynamic and functional balance abilities were evaluated by using
      computerized posturography. We tested the subjects before and after the four-week
      rehabilitation program. RESULTS: After the four-week treatment, for joint
      reposition sense evaluation, external 75% angle evaluation was done, revealing
      that the group with the application of foot orthotics improved by -1.07+/-1.64 on
      average, showing no significant difference between the two groups (p>0.05).
      Static, dynamic and functional balancing abilities using balance masters were
      evaluated, revealing that the two groups improved in some items, but showing no
      significant difference between them (p>0.05). CONCLUSION: This study found that
      athletes with chronic ankle instability who had foot orthotics applied for four
      weeks improved their proprioceptive and balancing abilities, but did not show
      additional treatment effects compared with rehabilitation exercise treatment.

PMID- 24020034
TI  - Improvement in anxiety and pain after whole body whirlpool hydrotherapy among
      patients with myofascial pain syndrome.
AB  - OBJECTIVE: To evaluate the effect of the Whirlpool hydrotherapy on pain and
      anxiety in chronic myofascial pain syndrome (MPS) patients, compared to the
      conventional hydrocollator pack therapy. METHODS: Forty-one subjects who have MPS
      in the upper trapezius muscles without depression were recruited. The patients
      were randomly assigned into two groups: the whirlpool therapy group whose bodies
      were immersed in a whirlpool bath at 34C-36C for 30 minutes; the hydrocollator
      group who took a 30-minute application of a standard hot hydrocollator pack.
      Patients in both groups received therapy three days a week for 2 weeks and
      underwent several evaluations at baseline and after treatment. The variables we
      analyzed during evaluations were as follows: the primary outcome we considered
      was pain severity using a visual analogue scale. And the secondary outcomes
      examined included anxiety using the Korean version of the Beck Anxiety Inventory
      and quality of life (QoL) using the Korean version of the World Health
      Organization QoL Assessment, Brief Form. All follow-up values were compared with
      the baseline values. RESULTS: The baseline parameters did not show significant
      differences between two groups. And after 2-week treatment, both groups revealed
      significant improvement in anxiety levels and QoL, as well as in pain. However,
      the improvement on pain (p=0.002) and anxiety (p=0.010) was significantly greater
      in the whirlpool group, compared to the hydrocollator group. CONCLUSION: The
      whirlpool hydrotherapy can be used as a more effective therapeutic method to
      reduce pain and anxiety in chronic MPS patients without depression.

PMID- 24020036
TI  - Plain abdominal radiograph as an evaluation method of bowel dysfunction in
      patients with spinal cord injury.
AB  - OBJECTIVE: To evaluate the usefulness of plain abdominal radiography as an
      evaluation method for bowel dysfunction in patients with spinal cord injury
      (SCI). METHODS: Forty-four patients with SCI were recruited. Patients were
      interviewed about their clinical symptoms, and the constipation score and Bristol
      stool form scale were assessed. The colon transit time (CTT) was measured by
      using radio-opaque markers (Kolomark). The degree of stool retention and the
      presence of megacolon or megarectum were evaluated using plain abdominal
      radiographs. We examined the relationship between clinical aspects and CTT and
      plain abdominal radiography. RESULTS: The constipation scores ranged from 1 to
      13, and the average was 4.19+/-3.11, and the Bristol stool form scale ranged from
      1 to 6, with an average of 4.13+/-1.45. CTTs were 19.3+/-16.17, 19.3+/-13.45,
      15.32+/-13.15, and 52.42+/-19.14 in the right, left, rectosigmoid, and total
      colon. Starreveld scores were 3.4+/-0.7, 1.8+/-0.86, 2.83+/-0.82, 2.14+/-1, and
      10.19+/-2.45 in the ascending, transverse, descending, rectosigmoid, and total
      colon. Leech scores were 3.28+/-0.7, 2.8+/-0.8, 2.35+/-0.85, and 8.45+/-1.83 in
      the right, left, rectosigmoid, and total colon. The number of patients with
      megacolon and megarectum was 14 (31.8%) and 11 (25%). There were statistically
      significant correlations between the total CTT and constipation score (p<0.05),
      and Starreveld and Leech scores (p<0.05). Significant correlations were observed
      between each segmental CTT and the segmental stool retention score (p<0.05).
      CONCLUSION: Plain abdominal radiography is useful as a convenient and simple
      method of evaluation of bowel dysfunction in patients with SCI.

PMID- 24020035
TI  - Ischemic compression after trigger point injection affect the treatment of
      myofascial trigger points.
AB  - OBJECTIVE: To investigate the effects of trigger point injection with or without
      ischemic compression in treatment of myofascial trigger points in the upper
      trapezius muscle. METHODS: SIXTY PATIENTS WITH ACTIVE MYOFASCIAL TRIGGER POINTS
      IN UPPER TRAPEZIUS MUSCLE WERE RANDOMLY DIVIDED INTO THREE GROUPS: group 1 (n=20)
      received only trigger point injections, group 2 (n=20) received trigger point
      injections with 30 seconds of ischemic compression, and group 3 (n=20) received
      trigger point injections with 60 seconds of ischemic compression. The visual
      analogue scale, pressure pain threshold, and range of motion of the neck were
      assessed before treatment, immediately after treatment, and 1 week after
      treatment. Korean Neck Disability Indexes were assessed before treatment and 1
      week after treatment. RESULTS: We found a significant improvement in all
      assessment parameters (p<0.05) in all groups. But, receiving trigger point
      injections with ischemic compression group showed significant improvement as
      compared with the receiving only trigger point injections group. And no
      significant differences between receiving 30 seconds of ischemic compression
      group and 60 seconds of ischemic compression group. CONCLUSION: This study
      demonstrated the effectiveness of ischemic compression for myofascial trigger
      point. Trigger point injections combined with ischemic compression shows better
      effects on treatment of myofascial trigger points in the upper trapezius muscle
      than the only trigger point injections therapy. But the duration of ischemic
      compression did not affect treatment of myofascial trigger point.

PMID- 24020037
TI  - The therapeutic effect of neurologic music therapy and speech language therapy in
      post-stroke aphasic patients.
AB  - OBJECTIVE: To investigate the therapeutic effect of neurologic music therapy
      (NMT) and speech language therapy (SLT) through improvement of the aphasia
      quotient (AQ) in post-stroke aphasic patients. METHODS: Twenty-one post-stroke,
      nonfluent aphasia patients who had ischemic/hemorrhagic stroke on radiologic
      evaluation were divided into the NMT and SLT groups. They received NMT and SLT
      for 1 month. Language function was assessed by Korean version-Western Aphasia
      Battery before and after therapy. NMT consisted of therapeutic singing and
      melodic intonation therapy, and SLT consisted of language-oriented therapy.
      RESULTS: Significant improvements were revealed in AQ, repetition, and naming
      after therapy in the NMT group and improvements in repetition in the SLT group of
      chronic stroke patients (p<0.05). There were significant improvements in language
      ability in the NMT group of subacute stroke patients. However, there was no
      significant improvement in the SLT group of subacute stroke patients. CONCLUSION:
      We concluded that the two therapies are effective treatments in the chronic stage
      of stroke and NMT is effective in subacute post-stroke aphasic patients.

PMID- 24020038
TI  - Adrenomyeloneuropathy presenting with adrenal insufficiency.
AB  - Adrenomyeloneuropathy (AMN), one of the variants of X-linked adrenoleukodystrophy
      (ALD), is inherited peroxisomal disorder associated with the accumulation of very
      long chain fatty acids (VLCFA). AMN is characterized primarily by involvements of
      long ascending and descending tracts of the spinal cord and peripheral
      neuropathy, which leads to spastic paraparesis and urinary and erectile
      dysfunction. We experienced the AMN case of a 33-year-old man presenting
      bilateral progressive spastic paraparesis, impotence and urge incontinence with
      primary adrenal failures, as confirmed by increased serum of VLCFA
      concentrations. Considering that somatosensory evoked potentials in posterior
      tibial nerve was the only abnormal finding in electrophysiologic findings when
      compared with the severe spastic gait pattern shown, it is necessary to follow up
      with electrophysiologic studies. 

PMID- 24020039
TI  - Multiorgan with renal infarction following treatment of cerebral infarction.
AB  - Acute renal infarction is a rare disease and it is often difficult to make a
      clinical diagnosis due to the non-specific clinical presentations and lack of the
      physicians' awarenesses. We experienced a case of a 72-year-old man who was
      diagnosed as multiorgan with renal infarction during the bridge therapy of
      cerebral infarction with atrial fibrillation. Computed tomogram (CT) with
      intravenous contrast of the abdomen and pelvis revealed left renal infarction
      with renal artery occlusion, multifocal splenic infarction, and ischemic colitis
      on rectum and sigmoid colon. The patient was treated with low molecular weight
      heparin for 10 days, his symptoms were improved and laboratory findings were
      normalized. Follow-up CT was performed on the 43th day, there were persisted left
      renal infarction with atrophic change shown and the splenic perfusion was
      improved. 

PMID- 24020040
TI  - Tuberculous tenosynovitis and ulnar bursitis of the wrist.
AB  - Tuberculous infection of the hand is a rare form of extrapulmonary tuberculosis
      that, left untreated, can cause serious joint and tendon damage. We report the
      case of a 65-year-old male patient who presented with an insidious flexor
      weakness of the fifth finger but without any history of trauma. Magnetic
      resonance imaging revealed a partial tear of the fifth finger flexor tendon with
      a fluid collection in the tendon sheath and in the flexor compartment along the
      ulnar side. Under ultrasound guidance, this fluid collection was aspirated and
      analyzed for Mycobacterium tuberculosis using polymerase chain reaction. The
      assay was positive for the microorganism, confirming the diagnosis of tuberculous
      tenosynovitis and ulnar bursitis of the wrist. The early suspicion and diagnosis
      of this extrapulmonary disease facilitated anti-tuberculous chemotherapy and
      helped avoid a hasty injection of corticosteroid. 

PMID- 24020041
TI  - Compressive neuropathy of the posterior tibial nerve at the lower calf caused by
      a ruptured intramuscular baker cyst.
AB  - Baker cyst is an enlargement of the gastrocnemius-semimembranosus bursa.
      Neuropathy can occur due to either direct compression from the cyst itself or
      indirectly after cyst rupture. We report a unique case of a 49-year-old man with
      left sole pain and paresthesia who was diagnosed with posterior tibial neuropathy
      at the lower calf area, which was found to be caused by a ruptured Baker cyst.
      The patient's symptoms resembled those of lumbosacral radiculopathy and tarsal
      tunnel syndrome. Posterior tibial neuropathy from direct pressure of ruptured
      Baker cyst at the calf level has not been previously reported. Ruptured Baker
      cyst with resultant compression of the posterior tibial nerve at the lower leg
      should be included in the differential diagnosis of patients who complain of calf
      and sole pain. Electrodiagnostic examination and imaging studies such as
      ultrasonography or magnetic resonance imaging should be considered in the
      differential diagnosis of isolated paresthesia of the lower leg. 

PMID- 24020042
TI  - Postpartum sacral stress fracture mimicking lumbar radiculopathy in a patient
      with pregnancy-associated osteoporosis.
AB  - Postpartum sacral fracture is relatively rare, and its diagnosis is often
      delayed. We herein report such a case of a 28-year-old patient who presented with
      an insidious-onset lower back pain, left buttock pain, and radicular symptoms
      mimicking lumbar radiculopathy. Laboratory tests showed a decreased 25-hydroxy
      vitamin D level, and the bone mineral densitometry of both femurs was below the
      expected range. Plain radiographs of the lumbar spine and pelvis showed no
      definite abnormality, but lumbosacral spinal magnetic resonance imaging
      identified a left sacral fracture. Symptoms were alleviated with rest and oral
      analgesic treatment. 

PMID- 24020043
TI  - Treatment of chronic isolated finger flexor tenosynovitis through 50% dehydrated
      alcohol installation.
AB  - The isolated idiopathic finger flexor tenosynovitis is a rare condition, related
      to diversed etiologies. The traditional treatment of flexor tenosynovitis
      includes medications and injection of steroids. If the conservative treatment is
      not effective, surgical management is usually recommended. And alcohol
      installations have been rarely performed. We are reporting an extremely rare case
      of a 56-year-old man who had chronic idiopathic isolated finger flexor
      tenosynovitis which was treated through alcohol injections. The patient had not
      yet been treated despite of medication and serial injections of steroid. We
      performed 1 mL of 50% ethanol injection for the initial treatment and the second
      injection was done in the same way 10 months later due to the improvements of the
      patient's clinical symptoms and images of the follow-up ultrasonography. As a
      result, the authors suggest alcohol installation as an alternative non-surgical
      treatment for flexor tenosynovitis when other conservative managements are not
      effective enough. 

PMID- 24020044
TI  - Holmes tremor after brainstem hemorrhage, treated with levodopa.
AB  - Holmes tremor is a rare movement phenomenon, with atypical low-frequency tremor
      at rest and when changing postures, often related to brainstem pathology. We
      report a 70-year-old female patient who was presented with dystonic head and
      upper limb tremor after brainstem hemorrhage. The patient had experienced a
      sudden onset of left hemiparesis and right facial paralysis. Brain magnetic
      resonance imaging showed an acute hemorrhage from the brachium pontis through the
      dorsal midbrain on the right side. Several months later, the patient developed
      resting tremor of the head and left arm, which was exacerbated by a sitting
      posture and intentional movement. The tremor showed a regular low-frequency (1-2
      Hz) for the bilateral sternocleidomastoid and cervical paraspinal muscles at
      rest. The patient's symptoms did not respond to propranolol or clonazepam, but
      gradually improved with levodopa administration. Although various remedies were
      attempted, overall, the results were poor. We suggest that levodopa might be a
      useful remedy for Holmes tremor. The curative or relieving effect of the
      dopaminergic agent in Holmes tremor needs more research. 

PMID- 24020045
TI  - Spontaneous perirenal hemorrhage in cauda equina syndrome: a case report.
AB  - Neurogenic bladder is a common cause of acute pyelonephritis (APN) in cauda
      equina syndrome (CES). Perirenal hemorrhage, a rare complication of APN, can be a
      life-threatening condition. To our knowledge, there is no previous report of
      perirenal hemorrhage as a complication of APN in CES. A 57-year-old male,
      diagnosed with CES, due to a L3 burst fracture 3 months earlier, was presented
      with fever and chills. His diagnosis was APN due to neurogenic bladder. After
      treatment for APN, he was transferred to the department of rehabilitation
      medicine for management of his CES. Because of large post-voiding residual urine
      volumes, he performed self-catheterization after voiding. However, he presented
      again with fever and chills, and recurrent APN was diagnosed. On the third day of
      antibiotic treatment, he had acute abdominal pains and hypovolemic shock.
      Abdominal computed tomography and angiography showed left APN and a perirenal
      hematoma with left renal capsular artery bleeding. After embolization of the left
      renal capsular artery, no further active bleeding occurred. Because APN due to
      neurogenic bladder can lead to critical complications, such as perirenal
      hemorrhage, the physician should pay attention to the early diagnosis and
      treatment of urinary tract infection and the management of neurogenic bladder
      after CES. 

PMID- 24020046
TI  - H7N9 Influenza: The Emerging Infectious Disease.
AB  - Influenza virus infection is a common respiratory pathogen. Emerging of new
      atypical influenza is usually a big public health threat. H7N9 bird flu is the
      newest atypical influenza virus infection that has just been reported since early
      2013. The emerging of this new disease occurred in China and becomes the present
      focus for possible worldwide pandemic. In this specific article, the author will
      discus and describe on epidemiology, symptomatology, pathology, diagnosis,
      treatment, and prevention of this new bird flu. The literature researching by
      PubMed and Google is used for data gathering in this collective review. 

PMID- 24020047
TI  - Prion diseases in humans: oral and dental implications.
AB  - Prion diseases are a group of neurodegenerative disorders characterized by
      accumulation of abnormal prion proteins in the central nervous system. The prions
      resist conventional sterilization procedures especially when infected tissue
      becomes dried onto metal or glass surfaces. This article, a review of literature
      collected using Pubmed as search engine, describes the oral manifestations of
      prion diseases in addition to studying the possibility of cross contamination in
      the dental office. The article emphasizes the importance for dentists to be aware
      of these diseases, to identify the high-risk patients by obtaining adequate
      medical history and to know the appropriate deactivation procedures to be
      followed. 

PMID- 24020049
TI  - Diagnostic Imaging in Pott's Disease of the spine.

PMID- 24020048
TI  - Pott's Spine: Diagnostic Imaging Modalities and Technology Advancements.
AB  - Spinal tuberculosis (TB) or Pott's spine is the commonest extrapulmonary
      manifestation of TB. It spreads through hematogenous route. Clinically, it
      presents with constitutional symptoms, back pain, tenderness, paraplegia or
      paraparesis, and kyphotic or scoliotic deformities. Pott's spine accounts for 2%
      of all cases of TB, 15% of extrapulmonary, and 50% of skeletal TB. The
      paradiscal, central, anterior subligamentous, and neural arch are the common
      vertebral lesions. Thoracic vertebrae are commonly affected followed by lumbar
      and cervical vertebrae. Plain radiographs are usually the initial investigation
      in spinal TB. For a radiolucent lesion to be apparent on a plain radiograph there
      should be 30% of bone mineral loss. Computed tomographic scanning provides much
      better bony detail of irregular lytic lesions, sclerosis, disc collapse, and
      disruption of bone circumference than plain radiograph. Magnetic resonance
      imaging (MRI) is the best diagnostic modality for Pott's spine and is more
      sensitive than other modalities. MRI frequently demonstrates disc
      collapse/destruction, cold abscess, vertebral wedging/collapse, marrow edema, and
      spinal deformities. Ultrasound and computed tomographic guided needle aspiration
      or biopsy is the technique for early histopathological diagnosis. Recently, the
      coexistence of human immunodeficiency virus infections and TB has been increased
      globally. In recent years, diffusion-weighted MRI (DW-MRI) and apparent diffusion
      coefficient values in combination with MRI are used to some extent in the
      diagnosis of spinal TB. We have reviewed related literature through internet. The
      terms searched on Google scholar and PubMed are TB, extrapulmonary TB, skeletal
      TB, spinal TB, Pott's spine, Pott's paraplegia, MRI, and computed tomography
      (CT). 

PMID- 24020050
TI  - Comparison of early and delayed laparoscopic cholecystectomy for acute
      cholecystitis: experience from a single center.
AB  - BACKGROUND: Cholecystectomy for symptomatic gallstones is mainly performed after
      the acute cholecystitis episode settles because of the fear of higher morbidity
      and conversion from laparoscopic cholecystectomy to open cholecystectomy during
      acute cholecystitis. AIMS: To evaluate the safety and feasibility of laparoscopic
      cholecystectomy for acute cholecystitis and to compare the results with delayed
      cholecystectomy. MATERIALS AND METHODS: This was a prospective and randomized
      study. For patients assigned to early group, laparoscopic cholecystectomy was
      performed as soon as possible within 72 hours of admission. Patients in the
      delayed group were treated conservatively and discharged as soon as the acute
      attack subsided. They were subsequently readmitted for elective laparoscopic
      cholecystectomy 6-12 weeks later. RESULTS: There was no significant difference in
      the conversion rates, postoperative analgesia requirements, or postoperative
      complications. However, the early group had significantly more blood loss, more
      operating time, and shorter hospital stay. CONCLUSION: Early laparoscopic
      cholecystectomy within 72 hours of onset of symptoms has both medical as well as
      socioeconomic benefits and should be the preferred approach for patients managed
      by surgeons with adequate experience in laparoscopic cholecystectomy.

PMID- 24020051
TI  - Impact of minimally invasive/bariatric surgery fellowship on perioperative
      complications and outcomes in the first year of practice.
AB  - BACKGROUND: Several reports have described worse perioperative outcomes of
      laparoscopic gastric bypass procedure during learning curve, which improved after
      completion of one-year fellowship training. AIMS: The aim of this study was to
      evaluate the immediate impact of fellowship training on perioperative
      complications and outcomes of various bariatric procedures. MATERIALS AND
      METHODS: One hundred initial patients who underwent laparoscopic gastric banding,
      laparoscopic Roux-en-Y gastric bypass, laparoscopic vertical sleeve gastrectomy,
      and robotically-assisted laparoscopic biliopancreatic diversion with duodenal
      switch by a single fellowship trained surgeon were analyzed. RESULTS: Overall
      average Body Mass Index (BMI) of the patients was 45.9 kg/m(2), age was 47.5
      years, and the American Society of Anesthesiologist Score was 2.89. There were no
      intraoperative, major 30-day complications, or open conversions. Average
      operative time was 62 minutes in gastric banding, 160 minutes in gastric bypass,
      119 minutes in vertical sleeve gastrectomy, and 320 minutes in biliopancreatic
      diversion. Length of stay ranged from 0.5 day after gastric banding to 3.9 days
      after biliopancreatic diversion. The perioperative complications and outcomes are
      comparable with those reported by experienced surgeons. No mortality occurred in
      this series. CONCLUSIONS: Bariatric fellowship ensured skills acquisition for new
      surgeons to safely and effectively perform various types of bariatric operations,
      with minimal perioperative complications and excellent outcomes.

PMID- 24020052
TI  - Peak expiratory flow rate of healthy school children living at high altitude.
AB  - BACKGROUND: Anthropometric and socioeconomic factors are known to influence peak
      expiratory flow rate, but the effect of altitude has not been established
      decisively, due to conflicting results of various studies. AIM: This study was
      conducted to evaluate the effect of altitude on peak expiratory flow rate of
      healthy school children. MATERIALS AND METHODS: A cross-sectional study was
      conducted in which the peak expiratory flow rate of a group of 290 school
      children (140 male and 150 female), aged 7-14 years, residing in Shimla (altitude
      2150 meters), were compared with the results obtained in an age- and sex-matched
      control group, consisting of 280 school children (138 male and 142 female),
      residing in Patiala (altitude 278 meters). Mini Wright Peak Flow Meter was used
      for the study. RESULTS: The mean peak expiratory flow rate value of boys at high
      altitude (265 +/- 92.6 L/min) was significantly higher than those in plain areas
      (245 +/- 82.1 L/min). Similarly, the mean peak expiratory flow rate of highlander
      girls (250.4 +/- 70.2 L/min) was significantly higher than girls of plains (232.6
      +/- 65 L/min). CONCLUSION: The study suggests that besides anthropometric and
      socioeconomic factors, altitude is an important determinant of lung function.

PMID- 24020053
TI  - Correlation of Lip Prints with Gender, ABO Blood Groups and Intercommissural
      Distance.
AB  - BACKGROUND: In forensics, the mouth allows for a myriad of possibilities. Lip
      print on glass or cigarette butt found at crime scenes may link to a suspect.
      Hence, a dentist has to actively play his role in personal identification and
      criminal investigation. AIMS: To investigate the uniqueness of the lip print
      patterns in relation to gender, ABO blood groups and intercommissural distance
      (ICD). MATERIALS AND METHODS: The study was conducted on 208 randomly selected
      students. The lip print of each subject was obtained and pattern was analyzed
      according to Tsuchihashi classification. The blood group and ICD at rest position
      was recorded for each. RESULTS: The study showed that Type II (branched) lip
      pattern to be most prominent. The B+ blood group was the most common in both
      genders and the ICD is higher in males. The lip print pattern does not show any
      correlation between ABO blood groups, gender, and ICD. CONCLUSIONS: The lip print
      pattern shows no correlation with gender, ABO blood groups, or ICD. Further
      studies with larger samples are required to obtain statistical significance of
      this correlation.

PMID- 24020056
TI  - An Indian Perspective on HIV-associated Lymphomas.

PMID- 24020054
TI  - Human immunodeficiency virus - associated lymphomas: a neglected domain.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) associated lymphoma is an
      important public health concern; however, the epidemiological data available from
      India is sparse. AIMS: The present study was carried out at a tertiary cancer
      care center in South India to analyze the scenario of HIV-associated lymphoma.
      MATERIALS AND METHODS: This was a retrospective observational study conducted at
      our center, on consecutive patients diagnosed with HIV-associated lymphoma, from
      January 2008 to December 2012. RESULTS: A total of 44 patients were diagnosed
      with HIV-associated lymphoma, of which 18 opted for treatment. There were 11
      males and 7 females in the study population. Median interval from the diagnosis
      of HIV infection to diagnosis of lymphoma was 18 months. Median CD4 count at the
      time of lymphoma diagnosis was 218/mm(3). Five patients had Hodgkin's lymphoma,
      and the rest had non-Hodgkin's lymphoma. Five out of 18 (28%) patients in the
      present study expired during treatment. Ten (55.5%) patients are alive and
      lymphoma free, with a median follow up of 18 months. CONCLUSIONS: More than half
      of our treated patients are lymphoma free with a median follow up of 18 months;
      hence treatment of patients with HIV-associated lymphoma should be encouraged.

PMID- 24020058
TI  - Vertebral artery dissection and lateral medullary stroke associated with neck
      trauma and clonidine withdrawal.

PMID- 24020057
TI  - In vivo Technique for Cellular Calcium Waves Documentation: A Light Microscopy
      Method.
AB  - BACKGROUND: We are introducing a novel in vivo technique to document cellular
      calcium deposits, which reflect a snapshot of the effect of calcium wave
      propagation. This technique however is not advocated enough to replace the
      accuracy and resolution of the confocal laser technique. Light microscopy
      equipment, calcium chelators and a histological calcium staining kit are
      essential. AIMS: The purpose of this study is to introduce the use of standard
      light microscopy to display in vivo ionic cellular calcium deposits. MATERIALS
      AND METHODS: Oxalic Acid (OA) (100 millimol) was the calcium chelator used in the
      study. This substance was injected into the dog right atrial tissue in vivo in an
      area of 1 cm(2). Samples were fixed and stained by the calcium specific von Kossa
      protocol. RESULTS AND CONCLUSIONS: Histological slides demarcated the
      intracellular calcium as black dots. Heterogeneity of calcium deposits mimicked
      images of both, the calcium sparks and calcium waves theories. This light
      microscopy technique could expand the number of experimental studies in the
      function of cellular calcium physiology.

PMID- 24020059
TI  - Molecular basis of mechanisms of steroid resistance in children with nephrotic
      syndrome.
AB  - Steroid therapy, due to a wide range of anti-inflammatory properties of steroids,
      is a basic field of treatment in many human diseases including the nephrotic
      syndrome in children. However, not all patients respond positively to therapy
      which divides them into steroid sensitive (SS) and steroid resistance (SR)
      individuals. Many potential factors associated with steroid resistance have been
      identified so far. It seems that genetic factors associated with glucocorticoid
      receptor alpha (GRalpha), the structure of heterocomplex of GR as well as
      glycoprotein P or cytochrome P450 may play a role in the induction of
      glucocorticoid resistance. Here we described several of the molecular mechanisms,
      which can regulate glucocorticoid sensitivity and resistance. Moreover, we
      presented genetic defects, which can lead to various effects of treatment and, in
      a longer perspective, enable clinicians to individualize therapies.

PMID- 24020060
TI  - Evaluation of antioxidant, antimutagenic, and lipid peroxidation inhibitory
      activities of selected fractions of Holarrhena floribunda (G. Don) leaves.
AB  - Exposure to environmental pollutants often leads to an upsurge in the production
      of reactive oxygen species (ROS). ROS oxidize cellular fatty acids to produce
      lipid peroxyl radicals, subsequently transformed into lipid peroxides, which
      decrease membrane fluidity and increase the activity of various enzymes
      implicated in degenerative diseases and cancer formation. Edible plants that
      contain exogenous compounds like curcumeroid, beta-carotene, turmeric, and so on,
      protect the aerobic cells from oxidation of free radicals. This study thus
      evaluates antioxidant and antimutagenic activities of ethyl acetate, aqueous and
      methanolic fractions of Holarrhena floribunda leaves. Inhibitory activities of
      the ethyl acetate fraction on Fe(2+)-induced lipid peroxidation in hen egg yolk;
      rat liver and brain tissues were also evaluated. The Allium cepa root assay was
      used to evaluate antimutagenic activity. Results showed that the ethyl acetate
      scavenged DPPH, OH*, and *O2(-) much stronger than other fractions, as evidenced
      by its lowest respective IC50 values. All the fractions displayed antimutagenic
      activities against cyclophosphamide-induced chromosomal aberrations. Likewise,
      all the fractions induced a reduction in mitotic index, a hallmark of
      cytotoxicity in the root meristem of Allium cepa. The decrease in mitotic index
      was most profound for the ethyl acetate fraction, which also demonstrated a
      significant lipid peroxidation inhibitory activity in the liver and brain
      homogenates, but not in egg yolk, compared with the ascorbic acid standard. In
      general, the results suggest that the ethyl acetate fraction might contain
      beneficial phytochemicals that should be explored as novel candidates for
      preclinical drug development.

PMID- 24020061
TI  - Effects of ketamine, propofol, and ketofol on proinflammatory cytokines and
      markers of oxidative stress in a rat model of endotoxemia-induced acute lung
      injury.
AB  - Intravenous lipopolysaccharide (LPS) leads to acute lung injury (ALI) in rats.
      The purpose of this study was to examine the anti-inflammatory and antioxidant
      efficacy of ketamine, propofol, and ketofol in a rat model of ALI. We induced ALI
      in rats via intravenous injection of LPS (15 mg kg(-1)). The animals were
      randomly separated into five groups: control, LPS only, LPS + ketamine (10 mg.kg(
      1).h(-1)), LPS + propofol (10 mg.kg(-1).h(-1)), LPS + ketofol (5 mg.kg(-1).h(-1)
      ketamine + 5 mg.kg(-1).h(-1) propofol). LPS resulted in an increase in the
      release of pro-inflammatory cytokines, mRNA expression related with inflammation,
      production of nitric oxide, and lipid peroxidation. Ketamine prevented the
      increase in markers of oxidative stress and inflammation mediators, both in
      plasma and lung tissue. Propofol decreased the levels of cytokines in plasma and
      lung tissue, whereas it had no effect on the IL-1-beta level in lung tissue.
      Ketamine downregulated mediators of lung tissue inflammation and reduced the
      level of circulating cytokines and protected lung tissue against lipid
      peroxidation. Ketofol decreased the level of TNF-alpha and IL-1beta in plasma, as
      well as expression of cyclooxygenase-2 mRNA and the nitrate/nitrite level in lung
      tissue. The results of this investigation support the hypothesis that ketamine
      may be effective in preventing ALI.

PMID- 24020063
TI  - Guest editorial-selected papers from the 2012 IEEE International Solid-State
      Circuits Conference (ISSCC).

PMID- 24020062
TI  - Guest editorial-ISCAS 2012 special issue.

PMID- 24020064
TI  - In this issue, we "focus" on outcomes.

PMID- 24020065
TI  - A call to action: expanded research agenda for women's health.

PMID- 24020066
TI  - India's amended trials regulations spark research exodus.

PMID- 24020067
TI  - Cell-free DNA screening for trisomy is rolled out in Israel.

PMID- 24020068
TI  - Cairo mourns the dead after violent crackdown.

PMID- 24020070
TI  - Host response: true to their family name.

PMID- 24020069
TI  - Back to the future.

PMID- 24020071
TI  - Bacterial pathogenesis: limiting DNA repair.

PMID- 24020072
TI  - Uncovering the mysteries of  hantavirus infections.
AB  - Hantaviruses are negative-sense single-stranded RNA viruses that infect many
      species of rodents, shrews, moles and bats. Infection in these reservoir hosts is
      almost asymptomatic, but some rodent-borne hantaviruses also infect humans,
      causing either haemorrhagic fever with renal syndrome (HFRS) or hantavirus
      cardiopulmonary syndrome (HCPS). In this Review, we discuss the basic molecular
      properties and cell biology of hantaviruses and offer an overview of virus
      induced pathology, in particular vascular leakage and immunopathology.

PMID- 24020073
TI  - The non-canonical roles of clathrin and actin in pathogen internalization, egress
      and spread.
AB  - The role of clathrin in pathogen entry has received much attention and has
      highlighted the adaptability of clathrin during internalization. Recent studies
      have now uncovered additional roles for clathrin and have put the spotlight on
      its role in pathogen spread. Here, we discuss the manipulation of clathrin by
      pathogens, with specific attention to the processes that occur at the plasma
      membrane. In the majority of cases, both clathrin and the actin cytoskeleton are
      hijacked, so we also examine the interplay between these two systems and their
      role during pathogen internalization, egress and spread.

PMID- 24020075
TI  - A problem of persistence: still more  questions than answers?
AB  - The current antibiotic resistance crisis has led to increased pressure to
      prioritize strategies to tackle the issue, with a strong focus being placed on
      the development of novel antimicrobials. However, one major obstacle that is
      often overlooked is persister cells, which are refractory to antibiotic
      treatment. Tackling persistence is a challenge because these cell types are
      extremely difficult to study and, consequently, little is known about their
      physiology and the factors that lead to their emergence. Here, four experts
      contemplate the main physiological features that define persistence and the
      implications of persistence for antibiotic treatment regimens, and consider what
      the study of bacterial persistence has taught us about the heterogeneity of
      bacterial populations.

PMID- 24020076
TI  - Dominick P. DePaola: the 33rd President of the AADR, 2004-2005.

PMID- 24020077
TI  - Multiple thrombi in the ascending aorta usefulness of contrast transesophageal
      echocardiography in a case of Horton's aortitis.

PMID- 24020074
TI  - Modern clinical microbiology: new challenges and solutions.
AB  - In the twenty-first century, the clinical microbiology laboratory plays a central
      part in optimizing the management of infectious diseases and surveying local and
      global epidemiology. This pivotal role is made possible by the adoption of
      rational sampling, point-of-care tests, extended automation and new technologies,
      including mass spectrometry for colony identification, real-time genomics for
      isolate characterization, and versatile and permissive culture systems. When
      balanced with cost, these developments can improve the workflow and output of
      clinical microbiology laboratories and, by identifying and characterizing
      microbial pathogens, provide significant input to scientific discovery.

PMID- 24020079
TI  - General discussion.

PMID- 24020078
TI  - [The therapeutic effect of antireflux medicine combined with positive airways
      pressure on obstructive sleep apnea hypopnea syndrome with gastroesophageal
      reflux].
AB  - OBJECTIVE: To investigate the therapeutic effect of nasal continuous positive
      airways pressure (nCPAP) combined with antireflux medicine on obstructive sleep
      apnea hypopnea syndrome (OSAHS) with gastroesophageal reflux (GER). METHOD: Sixty
      patients with moderate to severe OSAHS with GER were simultaneously received PSG
      and esophageal pH monitoring and randomly divided into control group and
      treatment group with each group 30 patients. The control group were simply
      received nCPAP for every night. The treatment group were received the same
      treatment and combined antireflux medicine, with esomeprazole 40 mg/d and
      mosapride citrate 5 mg, 3 times a day,oral. Both the groups symptomatic status of
      OSAHS and GER were observed on the third day and the 14th day during therapy, and
      then the same tests above were repeated on the 14th day. RESULT: Compared with
      the control group, the symptomatic improvement rate of OSAHS on the third day and
      14th day during therapy,the symptomatic improvement rate of GER on the third day
      during therapy were increased with statistical significance in the treatment
      group (P<0.05), however, the difference of symptomatic improvement rate of GER
      between the two groups on the 14th day during therapy did not have statistical
      significance (P>0.05). Compared with those of the control group on the 14th
      therapeutic night, AHI, LSaO2, the percentage of time with pH<4, the longest
      reflux duration,reflux episodes and DeMeester scoring did not have statistical
      significance in the treatment group (P>0.05). CONCLUSION: nCPAP is the most
      effective method for patients suffering OSAHS associated with GER, but nCPAP used
      in conjunction with anti-reflux drugs do not improve efficacy.

PMID- 24020080
TI  - Journal of Law and Medicine: Consolidated index to volumes 1-20, 1993-2013.

PMID- 24020081
TI  - Editor's note regarding duplicated text.

PMID- 24020082
TI  - Heparan sulfates demonstrate potential for Alzheimer's disease therapy.

PMID- 24020084
TI  - Long-term pharmaceutical industry alliance formed in Japan.

PMID- 24020083
TI  - Small-molecule inhibitors prevent apoptotic signaling pathway in pancreatic b
      cells.

PMID- 24020085
TI  - Combating side effects of sulfonamides.

PMID- 24020086
TI  - Collaboration announced for development of biologics analysis.

PMID- 24020087
TI  - Partnership opens Translational Medicine Center in Suzhou.

PMID- 24020088
TI  - New method created to easily and safely detect prostate cancer.

PMID- 24020089
TI  - Agreement signed for co-promotion and marketing of liver-based DMPK services.

PMID- 24020090
TI  - LC-MS used for detection of caffeine in fingerprints.

PMID- 24020091
TI  - [How to proceed in obstetrics?].

PMID- 24020092
TI  - Isolation and characterization of luteal cells in buffalo (Bubalus bubalis).
AB  - The objective of the study was to evaluate the morphological and functional
      characteristics of luteal cells isolated from buffalo ovary. Luteal cells
      exhibited columnar morphology and contact inhibition at the stage of confluence.
      Protein concentrations increased linearly from Day 3 to Day 7 of culture. DNA
      concentrations increased from Day 3 to Day 5 and then declined to Day 7 of
      culture. PGF2alpha concentrations decreased progressively from Day 3 to Day 7 of
      culture. It was concluded that buffalo luteal cells could serve as an excellent
      model for studying the specific role of PGF2alpha in maternal recognition of
      pregnancy and implantation.

PMID- 24020093
TI  - Correlation of age and antimullerian hormone in assisted reproductive technology
      program outcome.
AB  - Increasing female literacy and employment have resulted in a clear rise in the
      age at which women conceive. As fertility starts to decline with advancing age
      more and more number of women are facing the problem of infertility and are
      seeking medical attention to over come this problem. This resulted in more number
      of women seeking medical help to over come the problem of Infertility. This age
      related decline in ovarian reserve is not uniform in all women of reproductive
      age. A number of ovarian reserve tests were developed to overcome this problem.
      But to date there is no ideal marker for predicting ovarian reserve and pregnancy
      outcome in assisted reproductive technology program (ART). Recent studies
      indicate that anti mullein hormone is a promising marker for predicting ovarian
      reserve and pregnancy out come. The aim of this study was to assess the influence
      of age on Anti-Mullerian Hormone (AMH) in ART program outcomes. Ninety-three
      subjects in the age group of 25 to 42 years were recruited to the study. All
      these subjects underwent controlled ovarian stimulation (COS) and later
      intracytoplasmic sperm injection (ICSI). Subjects were divided into four groups.
      AMH levels in positive and negative pregnancy subjects in the above and below
      35years age groups were compared. AMH levels were correlated with other ovarian
      reserve parameters and clinical pregnancy out come in both the age groups.
      Statistically significant differences were found in AMH levels between positive
      and negative pregnancy subjects in the age group of 35 and above, but not in the
      age group below 35 years. There were positive correlations between AMH and other
      ovarian reserve markers and clinical pregnancy outcome in this age group. AMH and
      the number of retrieved oocytes (r = 0.784, P < 0.01), Antral Follicle count
      (AFC) (r = 0.749, P < 0.01) and Mature Oocytes (MII) (r = 0.407, P < 0.01)
      followed by Grade-I Embryos (r = 0.433, P < 0.01). The current study revealed
      that AMH levels are better correlated with ovarian reserve and clinical pregnancy
      out come in subjects aged 35 years and above.

PMID- 24020094
TI  - Heart rate variabilty changes during first week of acclimatization to 3500 m
      altitude in Indian military personnel.
AB  - Acute exposure to hypobaric hypoxia induces the changes in autonomic control of
      heart rate. Due to emergencies or war like conditions, rapid deployment of Indian
      military personnel into high altitude frequently occurs. Rapid deployment to high
      altitude soldiers are at risk of developing high altitude sickness. The present
      study was conducted to evaluate the acute exposure to high altitude hypobaric
      hypoxia (3500 m altitude) on the autonomic nervous control of heart rate in
      Indian military personnel during first week of acclimatization Indices of heart
      rate variability (viz; R-R interval, total power, low frequency, high frequency,
      ratio of low to high frequency) and pulse arterial oxygen saturation were
      measured at sea level and 3500m altitude. Power spectrum of heart rate
      variability was quantified by low frequency (LF: 0.04-0.15 Hz) and high frequency
      (HF: 0.15-0.5 Hz) widths. The ratio of LF to HF was also assessed as an index of
      the sympathovagal balance. Mean R-R interval decreased significantly on day 2 on
      induction to altitude which tended to increase on day 5. Total power (TP)
      decreased high altitude and tended to recover within a week. Both HF and LF power
      showed decrement at 3500m in comparison to sea level. The ratio of LF to HF
      (LF/HF) at 3500m was significantly higher at 3500m. SpO2 values decreased
      significantly (P < 0.05) at high altitude on day-2 which increased on day-5. We
      conclude that autonomic control of the heart rate measured by heart rate
      variability was altered on acute induction to 3500m which showed a significant
      decrease in parasympathetic tone and increase in sympathetic tone, then
      acclimatization seems to be characterized by progressive shift toward a higher
      parasympathetic tone.

PMID- 24020096
TI  - Poincare plot of heart rate variability: an approach towards explaining the
      cardiovascular autonomic function in obesity.
AB  - Obesity has been shown to affect cardiovascular function. Heart rate variability
      (HRV) has been an accepted method of measuring cardiovascular autonomic function.
      The aim of the study is to evaluate the impact of obesity on HRV using Poincare
      plot (POP) analysis. A finding of sympathovagal imbalance in pre-obese adults in
      respiratory sinus arrhythmia (RSA) could provide important diagnostic information
      about early subclinical autonomic dysfunction in obesity. Thirty one obese (BMI
      26.84 +/- 2.47) adult males (25.42 +/- 7.86 years) were compared with 31 normal
      subjects (25.38 +/- 4.61 years). In all participants, anthropometric and blood
      pressure (BP) measurements were performed. After rest at supine position for 5
      minutes, they were asked to do control deep breathing for 1 minute. HRV was
      measured in terms of POP analysis. Differences in Resting heart rate (RHR) (P <
      or = 0.025), Pulse pressure (PP) (P < or = 0.048), SD1 (P < or = 0.042) and SD2
      (P < or = 0.039) of the POP between the two groups were significant. Correlation
      between Body mass index (BMI) and (PP) (p = 0.19); SD1 (p = 0.47) and SD2 (p =
      0.39) of the POP were significant in obese groups. Obesity is related to
      sympathovagal imbalance characterized by depressed parasympathetic tone and
      increased sympathetic activity. Nonlinear methods like POP permit simple
      assessment of autonomic function, despite measuring different aspects of HRV.

PMID- 24020095
TI  - Cardiovascular parasympathetic nervous system dysfunction in female rheumatoid
      arthritis patients.
AB  - The autonomic dysfunction has been reported in patients with (rheumatoid
      arthritis) RA and systemic lupus erythematosus (SLE) like connective tissue
      disorders and it may be due to the vasculitis of vasa nervorum and secondary
      amyloidosis. The pathogenesis may also have an immune component that affects
      autonomic functions. In the present study, three standard cardiovascular
      parasympathetic function tests were performed in 207 RA patients and in 106
      healthy controls. 14.45% patients were presented with symptoms related to
      cardiovascular autonomic dysfunction. Heart rate variation to deep breathing
      (DBD), standing (30:15 ratio), Valsalva ratio (VR) were found to be significantly
      reduced in RA patients and was weakly associated with female RA patients (r =
      0.165, p = 0.018) and was not correlated to disease duration, RF positivity &
      severity of the disease. In conclusion, this study has confirmed the presence of
      significant subclinical cardiovascular parasympathetic nervous dysfunction in RA
      patients and its positive association with female gender. Hence, inclusion of
      cardiovascular autonomic function tests in the routine clinical examination may
      be helpful in the early detection of autonomic dysfunction in RA.

PMID- 24020097
TI  - The influence of the 2:1 yogic breathing technique on essential hypertension.
AB  - In 2:1 breathing exhalation is twice of inhalation. The study was performed to
      study the influence of 2:1 yogic breathing technique on patients of essential
      hypertension. 30 patients of essential hypertension between ages of 20-50 years
      were selected. After a rest of 15-20 minutes in a comfortable sitting posture
      their baseline physiological parameters recorded on a digital polygraph were,
      Electromyogram (EMG), Galvanic skin response (GSR), Finger tip temperature (FTT),
      Heart rate(HR) and Respiratory rate(RR). Systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) were recorded by automated digital
      Sphygmomanometer. Then they were guided to do 2:1 breathing maintaining
      respiratory rate of around 6/min. Subjects were then instructed to do 2:1
      breathing twice a day for 5-7 minutes for next 3 months. Subjects reported back
      weekly for recording of BP. The physiological parameters of the subjects were
      assessed again by polygraph at the end of three months of practicing 2:1 yogic
      breathing. The mean fall of SBP over 12 weeks was 12 mm Hg (8%) and DBP was 7 mm
      Hg (7%). P value < 0.001 in both. After practicing 2:1 breathing for 3 months
      there was statistically significant reduction of SBP, DBP, HR RR, EMG, GSR and
      rise in FTT. The study showed that 2:1 breathing technique caused a comprehensive
      change in body physiology by altering various parameters that are governed by the
      autonomic nervous system. It is an effective modality for management of essential
      hypertension.

PMID- 24020098
TI  - Association of obesity and leptin with insulin resistance in type 2 diabetes
      mellitus in Indian population.
AB  - Obesity and diabetes mellitus are two modern epidemics. But their
      interrelationship is debated. Here we explored the probable association among
      obesity, leptin and insulin resistance in type 2 diabetes mellitus. 60 recent
      onset (< 5 years) diabetics and age-sex matched 33 non diabetic controls were
      assessed for physical and chemical parameters like Body Mass Index, abdominal
      circumference, waist/hip ratio, fasting blood glucose, insulin and leptin. Degree
      of insulin resistance was calculated by HOMA-IR method (Homeostatic Model
      Assessment). All the physical parameters showed positive correlation with leptin
      and the HOMA-IR score, strength of association being highest between insulin
      resistance and abdominal circumference. Leptin and insulin resistance showed no
      correlation. Findings were lower in controls. Study concluded that, obesity
      mainly central type might be responsible for insulin resistance in type 2
      diabetes mellitus where as leptin, a potential marker for obesity, may not. This
      perhaps points towards the multifactorial causation of insulin resistance in type
      2 diabetes mellitus.

PMID- 24020099
TI  - Antioxidant, anti-inflammatory and antinociceptive activities of essential oil
      from ginger.
AB  - Chemical compositions of ginger oil as well as its antioxidant, anti-inflammatory
      and antinociceptive potential were evaluated in the present study. The main
      constituents as detected by GC/MS analysis was alpha-zingiberene which
      constituted 31% of the total area, ar-curcumene (15.4%) and a -sesquiphellandrene
      (14.02%). Ginger oil scavenged superoxide, DPPH, hydroxyl radicals and inhibited
      tissue lipid peroxidation in vitro. Intraperitoneal administration of ginger oil
      was found to inhibit phorbol-12-myristate-13-acetate induced superoxide radicals
      elicited by macrophages. Oral administration of ginger oil for one month,
      significantly increased superoxide dismutase, glutathione and glutathione
      reductase enzymes level (P < 0.001) in blood of mice and glutathione-S
      transferase, glutathione peroxidase and superoxide dismutase enzymes in liver.
      Ginger oil produced significant reduction in acute inflammation produced by
      carrageenan and dextran and formalin induced chronic inflammation (P < 0.001). It
      also exhibited significant reduction in acetic acid induced writhing movements (P
      < 0.001). The present report revealed that ginger oil possesses antioxidant
      activity as well as significant anti-inflammatory and antinociceptive property.

PMID- 24020100
TI  - Effect of Dolichos biflorus on blood sugar and lipids in diabetic rats.
AB  - Diabetes mellitus is a chronic disease characterized by hyperglycemia and
      dyslipidemia, which leads to severe morbid complications. In view of the
      effectiveness of conventional herbal adjutants the present study was taken to
      assess the anti-diabetic and anti-lipidemic effect of Dolichos biflorus. 32
      healthy albino rats of either sex were randomly divided into 4 equal groups (I
      IV) each having 8 rats. Group I, control rats received only vehicular fluid while
      Group II received only Dolichos biflorus for the experimental period of 30 days.
      Diabetes was induced in Group II and Group IV rats by single intravenous dose of
      STZ and confirmed on 3rd day with fasting blood sugar (FBS) more than 250 mg/dl.
      Group III diabetic rats, received vehicular fluid while Group IV diabetic rats
      received Dolichos biflorus in single dose of 300 mg/kg body weight/day intra
      gastrically up to the experimental period of 30 days. FBS levels were assessed on
      1st, 8th, 15th, 22nd and 30th day. On last day overnight fasted rats were
      sacrificed for drawing the sample for lipid profile from beating heart and
      harvested for pancreatic tissue histology. Data obtained showed that FBS levels
      were decreased significantly when Dolichos biflorus was given to diabetic rats
      from mean +/- SD values 362 +/- 63.36 to 118 +/- 38.55 with p value < 001. S
      cholesterol and S. triglyceride levels were also decreased significantly with P
      value < 001. It was concluded that Dolichos biflorus has anti-diabetic and anti
      lipidemic effect at daily oral dose and can be used as an adjuvant for management
      of diabetes mellitus and its associated complications.

PMID- 24020101
TI  - Digit ratio (2D:4D) and performance in Indian swimmers.
AB  - It has been suggested that achievement in sports is correlated with a putative
      measure of prenatal testosterone the 2nd to 4th digit ratio (2D:4D). It has been
      shown that digit ratio (2D:4D) is negatively associated with prenatal
      testosterone, and it is also negatively associated with ability in sports. This
      study examined associations between 2D:4D and performance of both male and female
      National level Indian swimmers. Age matched non-sports personnel formed the
      control. Lengths of second and fourth digits were measured after scanning both
      hands and their ratio calculated. Our results show lower 2D:4D values in males
      compared to females (P < 0.05). Among male, but not female, swimmers had
      significantly (P < 0.05) lower 2D:4D ratio. Low 2D:4D in male swimmers suggests
      they are more prenatally programmed via long-lasting extra genital effects of
      testosterone. 2D:4D ratio could be used to identify young sports personnel who
      have potential to reach high levels of performance.

PMID- 24020103
TI  - Effect of 'Khaini'--a form of smokeless chewing tobacco on pulmonary functions.

PMID- 24020102
TI  - Validity of 20 meter multi-stage shuttle run test for estimation of maximum
      oxygen uptake in female university students.
AB  - Indirect protocols for determination of cardiorespiratory fitness in terms of
      VO2max have been developed to avoid the complicated experimental protocol of
      direct VO2max estimation especially in clinical setting. 20-meter multi stage
      shuttle run test (SRT) is one of such indirect protocols developed in Western
      population. Eighty eight (88) sedentary young healthy female university students
      (Age 22.8 +/- 1.79 years, Body height 159.0 +/- 4.28 cm and Body mass 52.47 +/-
      4.17 kg) of same socio-economic background were recruited in the study by simple
      random sampling from University of Calcutta, Kolkata, India to validate the
      applicability of SRT in the studied population. They were randomly separated into
      "study group" (N=58) on which the existing experimental protocol of SRT was
      tested and "confirmatory group" (N = 30) on which the modified equations were
      validated. VO2max of each participant was determined by direct procedure and
      indirect SRT method. The difference between the mean values of directly measured
      VO2max and indirectly predicted VO2max (PVO2max) in the "study group" was
      statistically significant (P < 0.001). Limit of agreement analysis revealed poor
      confidence level for application of current method of SRT in the studied
      population. However, VO2max was significantly correlated with age (r = 0.71, P <
      0.001), body mass (r = 0.58, P < 0.001), body height (r = 0.55, P < 0.001), speed
      (r = 0.92, P < 0.001) and PVO2max (r = 0.89, P < 0.001). Modified norms in the
      form of simple and multiple regression equations were applied in the Confirmatory
      Group. Results suggested a good agreement of the modified equations of SRT in
      this population with substantially small SEE. Hence, the currently proposed
      modified norms are recommended to predict VO2max in the studied population.

PMID- 24020104
TI  - How to manage specialty pharmacy when it's not so special anymore.

PMID- 24020105
TI  - Efficiencies, jobs, and staying the course. Interview by John Marcille.

PMID- 24020106
TI  - Will biomarkers be next leap forward in RA?

PMID- 24020107
TI  - It ain't easy being a patient.

PMID- 24020108
TI  - How will state exchanges handle cancer drugs?

PMID- 24020109
TI  - New sentinel lymph node mapping tool spots cancer with futuristic effectiveness.

PMID- 24020110
TI  - Physician-owned hospitals forced to plead their case.

PMID- 24020111
TI  - Climate of change.

PMID- 24020112
TI  - Preventing the cycle of teen abuse.

PMID- 24020113
TI  - They are what they eat.

PMID- 24020114
TI  - Let's go outside to play!

PMID- 24020115
TI  - At a glance: brain tumours in children.

PMID- 24020116
TI  - Hydration and children.

PMID- 24020117
TI  - Community file: neonate with torticollis.

PMID- 24020118
TI  - Tau pathology in diabetes mellitus.
AB  - Neurodegenerative tauopathy characterized by hyperphosphorylation tau has been
      implicated in the pathophysiology of diabetic central nervous system (CNS)
      complication. Emerging evidence has suggested that hyperphosphorylation tau is
      caused by an imbalance of protein kinase and phosphatase activity. This review
      focuses on the contributions of impaired insulin signaling to diabetes-related
      tauopathy through disrupting the balance of tau-related protein kinases and
      phosphatases. In addition, we describe tau pathology as a potential target for
      central neuronal degeneration in diabetes mellitus.

PMID- 24020119
TI  - Preparation and in vitro anti-tumor properties of toad venom extract-loaded solid
      lipid nanoparticles.
AB  - In this study, we prepared solid lipid nanoparticles (TV-SLNs) loaded with toad
      venom extract and investigated their anti-tumor effects in vitro in HeLa and SKOV
      3 cells. TV-SLNs were prepared using a cold homogenization technique, and the
      formulation was optimized by central composite design and response surface
      methods. The anti-tumor activities of TV-SLNs were evaluated by analyzing cell
      division and cell cycle distribution by using the MTT assay and flow cytometry.
      After incubation with TV-SLNs, the growth of both HeLa and SKOV-3 cells was
      inhibited significantly. The percentage of HeLa cells in G0/G1 phase decreased,
      whereas that in the S and G2/M phases increased. Thus, the S and G2/M phases were
      blocked after the incubation of HeLa cells with TV-SLNs for 24 h. In contrast,
      the percentage of SKOV-3 cells in G0/G1 phase increased and then decreased in S
      and G2/M phases, with the G0/G1 phase being blocked after incubation with TV-SLNs
      for 24 h. Our results demonstrate that TV-SLNs inhibited the fissiparism of HeLa
      and SKOV-3 cells in a time-and dose-dependent manner. TV-SLNs may be effective as
      a novel TV vaginal delivery system for the treatment of cervical and ovarian
      cancers.

PMID- 24020120
TI  - Stent-based delivery of decoy oligodeoxynucleotides against activator protein-1
      binding site decreased restenosis in rabbits.
AB  - The application of drug eluting stents (DES) significantly reduced the rate of
      restenosis but is associated with increased risk of late stage thrombosis. Thus,
      development of more effective and safer drugs for in stent delivery to inhibit
      restenosis is of great clinical interest. Decoy oligodeoxynucleotides against
      activator protein-1 (AP-1) binding site (dec-ODN) delivered with one time
      infusion or transfer have been shown to effectively inhibit neointimal
      proliferation and thickening. In this study, we delivered dec-ODN against AP-1 in
      stent and examined the inhibitory effects on restenosis. Synthetic dec-ODN
      targeting consensus AP-1 binding site was coated onto DESs. Thirty male rabbits
      were randomly divided into three groups: Control stent (CS), scrambled
      oligodeoxynucleotides (scr-ODN) stent and dec-ODN stent groups with 10 rabbits in
      each group. All stents were implanted in the abdominal aorta of rabbits. Eight
      weeks after stent implantation, the neointimal hyperplasia and re
      endothelialization in the abdominal aortas of implanted segments were examined as
      well as the expression of TGF-beta1 and TGF-beta1 target gene connective tissue
      growth factor (CTGF). Dec-ODN delivered in-stent significantly inhibited the mRNA
      and protein expression of TGF-beta1 and CTGF, as well as neointimal thickening
      and restenosis in abdominal aortas as compared to control (CS) and scr-ODN. Re
      endothelialization was not evidently affected by the delivery of Scr-ODN and dec
      ODN. Our data demonstrate that in-stent delivery of dec-ODN against AP-1
      effectively inhibited neointimal hyperplasia and support further investigation of
      DES/dec-ODN against AP-1 as a potential long-term therapeutic agent against in
      stent restenosis.

PMID- 24020121
TI  - Enhanced tumor accumulation and cellular uptake of liposomes modified with ether
      bond linked cholesterol derivatives.
AB  - Novel liposomal formulations based on cholesterol modification had been designed
      previously by our lab, but we found them with a poor stability and short half
      life, especially in blood circulation. The results might be attributed to the
      hydrolysis of ester linked cholesterol derivatives by esterase in plasma. Thus,
      in this study, we newly synthesized ether-linked cholesterol derivatives and
      compared them to other preparations. A comparison with the substrate cholesterol
      PEG2000-maleimide showed that ether-linked cholesterol-PEG2000-maleimide could
      relatively maintain integrity in serum, with only a small mottle emerging on TLC
      (thin-layer chromatography) plates through the experiment. Then a cell
      penetrating peptide TAT was attached to the distal end of CHO-PEG2000 to prepare
      liposomes and to further evaluate the two cholesterol derivatives. Optimized
      liposomes (65:35, lipid/cholesterol, molar ratio) composed of 3% CHO-PEG2000 and
      3% CHO-PEG2000-TAT showed good stability in 50%FBS (fetal bovine serum). In vitro
      experiments showed that as incubation time prolonged, ether-linked-TAT LIP showed
      a 3.67-fold higher uptake amount than ester-linked-TAT LIP. In vivo, ether-linked
      TAT LIP accumulated better in tumors and had a 40% higher cellular uptake amount.
      Altogether, we could conclude that our newly ether-linked cholesterol derivatives
      possessed better stability especially in blood circulation which led to increased
      tumor cellular uptake in vitro and in vivo. Our study may offer a better way in
      cholesterol modification to prepare functionalized liposomes.

PMID- 24020122
TI  - Pharmacokinetic profile of spectinomycin in rats.
AB  - Following intravenous (IV) administration, the pharmacokinetics of spectinomycin
      in rats was found to be on par with its profile in other mammalian species
      including humans with respect to its overall excretion and half-life at effective
      concentrations. This study, however, indicates that a small fraction of the
      spectinomycin dose is retained in peripheral tissues for a prolonged period of
      time at low concentrations.

PMID- 24020123
TI  - Propofol up-regulates Mas receptor expression in dorsal root ganglion neurons.
AB  - Mas is a functional binding site for angiotensin (Ang)-(1-7), a critical
      component of the renin-angiotensin system that is involved in processing
      nociceptive information. A recent study reported the localization of Mas in rat
      dorsal root ganglia (DRG) and demonstrated that Ang-(1-7) produced a dose
      dependent peripheral antinociceptive effect in rats through the Mas receptor by
      an opioid-independent mechanism. In the present study, we for the first time
      examined the effect of propofol on Mas expression in cultured DRG neurons. We
      treated rat DRG neurons with propofol at different concentrations (0.1, 0.5, 1, 5
      or 10 microM) for different length of time (0.5, 1, 2, 4 or 6 h) with or without
      transcription inhibitor actinomycin D or different kinase inhibitors. Propofol
      increased the Mas receptormRNA level in a statistically significant dose- and
      time-dependent manner within 4 h, which led to dose-dependent up-regulation of
      the Mas receptor protein level as well as Ang-(1-7) binding on the cell membrane.
      Actinomycin D (1 mg/ml) and p38 mitogen-activated protein kinase inhibitor
      PD169316 (25 microM) completely abolished the effect of propofol on Mas receptor
      expression in DRG neurons. In conclusion, we demonstrate that propofol markedly
      up-regulates Mas receptor expression at the transcription level in DRG neurons by
      a p38 MAPK-dependent mechanism. This study provides new insights into the
      mechanisms of action of propofol in peripheral antinociception, and suggests a
      new regulatory mechanism on the Ang-(1-7)/Mas axis in the peripheral nervous
      system.

PMID- 24020124
TI  - Lycopene protects against LPS-induced proinflammatory cytokine cascade in HUVECs.
AB  - The aim of the study was to explore whether lycopene protects against the
      activation of human umbilical vein endothelial cells (HUVECs) induced by a
      proinflammatory stimulus. HUVECs were pretreated with different concentrations of
      lycopene (1 microm or 10 microm), then incubated with 1 microg/ml LPS for 24 h.
      After an incubation, the mRNA and protein levels of proinflammatory cytokines
      (MCP-1, IL-6, VCAM-1), the expression KLF2, TLR4, ERK1/2 and NF-kappaB were
      assayed. The result showed that lycopene treatment significantly suppressed the
      response of HUVECs to LPS and reduced the levels of proinflammatory cytokines.
      Also, lycopene increased KLF2 expression, while it inhibited the activation TLR4
      and its downstream ERK and the NF-kappaB signaling pathway in HUVECs.

PMID- 24020125
TI  - Effects of supplementation with fish oil and n-3 PUFAs enriched egg yolk
      phospholipids on anhedonic-like response and body weight in the rat chronic mild
      stress model of depression.
AB  - Polyunsaturated fatty acids play an important role in the human organism. They
      guarantee a normal function of nervous cells, influence neurotransmission, and
      build some elements of cellular membranes. Several reports indicate an
      association between a deficiency of polyunsaturated fatty acids and depression.
      The aim of this study was to examine the effects of diet supplemented with fish
      oil, which is rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) and n-3
      PUFAs enriched phospholipids ("super lecithin") obtained from designed eggs on
      anhedonic-like response and body weight in the rat chronic mild stress (CMS)
      model of depression. The results showed that neither fish oil nor n-3 PUFAs
      enriched egg yolk phospholipids supplementation reversed disturbances caused by
      CMS, such as anhedonic-like state or reduction of body weight gain.

PMID- 24020126
TI  - Resveratrol inhibits NF-kB signaling through suppression of p65 and IkappaB
      kinase activities.
AB  - Resveratrol has been shown to possess multiple pharmacological activities
      including anti-tumor, anti-inflammation and immunomodulation, and participates in
      the regulation of the NF-kappaB signaling pathway. However, the mechanism of the
      NF-kappaB signaling pathway inhibited by resveratrol remains obscure. In this
      study, we first examined the effect of resveratrol on endogenous and TNF-alpha
      induced NF-kappaB activation, and found that resveratrol suppressed NF-kappaB
      activation in a dose dependent manner. Resveratrol reduced the transcriptional
      activity of p65, but neither affected the DNA-binding activity of NF-kappaB nor
      blocked the nuclear translocation of p65. Moreover, resveratrol had no effect on
      the expression level of IkappaBalpha protein and inhibited IkappaBalpha
      degradation. Further investigation revealed that resveratrol blocked the
      ubiquitination of NEMO and inhibited IkappaB kinase(beta)-mediated NF-kappaB
      activation. These results demonstrated that resveratrol effectively suppressed NF
      kappaB signaling through inhibiting the activities of NF-kappaB and IkappaB
      kinase. Therefore, resveratrol may provide a novel approach to treating
      inflammation-associated diseases and cancer.

PMID- 24020127
TI  - Antimicrobial activity of propolis special extract GH 2002 against multidrug
      resistant clinical isolates.
AB  - The need to discover and develop alternative therapies to treat multidrug
      resistant bacterial infections is timely. The aim of this study was to examine
      the antimicrobial potential of propolis, as a purified and concentrated special
      extract GH 2002, against clinical isolates of Streptococcus pyogenes, methicillin
      resistent Stapylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium
      (VRE) and Candida. Minimal inhibitory concentrations (MICs) and minimal
      microbicidial concentrations (MMCs) of propolis against microbial pathogens were
      evaluated using the broth microdilution method. Propolis extract GH 2002 revealed
      low MICs in the range of 0.03 to 2 mg/ml against S. pyogenes, S. aureus, E.
      faecium and Candida. A high bactericidal activity of propolis extract in the
      range of 0.06 to 1.0 mg/ml was determined for S. pyogenes and S. aureus, however
      propolis was not bactericidal against E. faecium. Propolis concentrations between
      0.6 and 2.4 mg/ml displayed fungicidal activity against different Candida
      species. Whereas all tested MRSA strains were highly susceptible against
      propolis, only minor activity was found against VRE strains. Time-kill curves
      demonstrated a high antimicrobial activity at low MICs already after few hours of
      incubation against reference strains, clinical antibiotic-susceptible strains,
      clinical antifungal susceptible strains as well as all tested clinical MRSA
      strains, but not against VRE strains. In conclusion, clinical drug-sensitive as
      well as some clinical multidrug-resistant microbial isolates, i.e. MRSA, were
      susceptible to propolis with different degrees of susceptibility. These results
      suggest that the special propolis extract GH2002 might be used in the development
      of alternative products for therapy of microbial infections.

PMID- 24020128
TI  - Antiherpetic activity of the traditionally used complex essential oil Olbas.
AB  - Essential oils of medicinal plants are increasingly of interest as novel drugs
      for antiherpetic agents, since herpes simplex virus (HSV) might develop
      resistance to commonly used antiviral drugs. The antiviral effect of Olbas, a
      traditionally used complex essential oil, and of cajuput oil, a major
      constitutent of Olbas, against HSV type 1 was examined. The antiviral activity of
      these essential oils was tested in vitro on monkey kidney cells using a plaque
      reduction assay. The 50% inhibitory concentration (IC50) of Olbas and cajuput oil
      for herpes simplex virus plaque formation was determined at 1.8 microg/ml and 7.5
      microg/ml, respectively. At noncytotoxic concentrations of these oils, plaque
      formation was significantly reduced by 99% for Olbas and 66% for cajuput oil. The
      selectivity index of 150 for Olbas against herpes simplex virus was superior to a
      rather low selectivity index for cajuput oil. The mode of antiviral action of
      these essential oils was assessed by time-on-addition assays. Herpesvirus was
      significantly inhibited by pretreatment with Olbas essential oil prior to
      infection of cells. These results indicate that Olbas affected the virus before
      adsorption, but not after penetration into the host cell, thus Olbas exerted a
      direct antiviral effect on HSV. A clearly time-dependent antiviral activity for
      Olbas and cajuput oil could be demonstrated. Considering the lipophilic nature of
      the Olbas complex essential oil mixture, which enables it to penetrate the skin,
      and a high selectivity index, Olbas might be suitable for topical treatment of
      herpetic infections.

PMID- 24020129
TI  - Risk factors for Clostridium difficile-associated diarrhea and the effectiveness
      of prophylactic probiotic therapy.
AB  - Measures for prevention of Clostridium difficile-associated diarrhea, a common
      nosocomial infection, in hospital settings are urgently needed. This study was
      conducted to identify the risk factors contributing to C. difficile-associated
      diarrhea and to evaluate the clinical benefit of probiotics in its prevention.
      The study included 2716 patients at least 20 years old who received an injected
      antibiotic at any time between February 2010 and February 2011; a total of 2687
      patients (98.9%) were assigned to the non-C. difficile-associated diarrhea group,
      and 29 patients (1.1%) were assigned to the C. difficile-associated diarrhea
      group. Univariate analysis revealed a significant difference between the two
      groups for the following factors: antibiotic therapy for > or = 8 days; enteral
      nutrition; intravenous hyperalimentation; fasting; proton pump inhibitor use; H2
      blocker use; and serum albumin < or = 2.9g/dL (p<0.05). Multivariate logistic
      regression analysis revealed a significant difference between the two groups for
      several factors. Antibiotic therapy for > or = 8 days, intravenous
      hyperalimentation, proton pump inhibitor use, and H2 blocker use were therefore
      shown to be risk factors for C. difficile-associated diarrhea. Prophylactic
      probiotic therapy was not shown to suppress the occurrence of C. difficile
      associated diarrhea.

PMID- 24020130
TI  - An improved, disposable indwelling intrauterine tube ("smit sleeve") not
      requiring retaining stitches for brachy-radiotherapy for carcinoma of the cervix.
AB  - OBJECTIVE: The objective was to improve the design of the indwelling-intrauterine
      tube (IIUT) for brachy-radiotherapy of cervical cancer or sleeve, specifically
      one that would not require stitching to retain it properly in the uterus for
      periods of one to two weeks and to ensure hygiene by making them disposable,
      thinner, lighter, more economical, as well as more user-friendly for doctor and
      patient alike, and to satisfy new developments in terms of computed tomography
      (CT) and magnetic resonance imaging (MRI) compatibility. MATERIALS AND METHODS:
      Injection moulding of carefully-selected medical grade polymers enabled ten
      improvements to the original sleeve; some were impossible to achieve with lathe
      turned items. The most important innovation was the addition of two delicate and
      very soft "wings" to the sleeves near the tips The sleeves were used in 50
      consecutive patients with advanced carcinoma of the cervix. Metal markers could
      be eliminated by adding barium to the polymers. RESULTS: Not a single sleeve fell
      out in any of the 50 patients. No complications related to the use of the sleeves
      were observed. These sleeves are now used exclusively in this clinic.
      CONCLUSIONS: The improvements were very successful; none fell out and no suturing
      was required, which made them still more cost-effective and more comfortable to
      patients.

PMID- 24020131
TI  - Impact of multimodal therapy on the survival of patients with newly diagnosed
      uterine carcinosarcoma.
AB  - PURPOSE: To investigate treatment outcomes of uterine carcinosarcoma (CS)
      patients who underwent complete surgical resection of all visible disease and
      platinum-based adjuvant chemotherapy (multimodal therapy). MATERIALS AND METHODS:
      The authors reviewed 127 uterine CS patients treated at this institution from
      1990 to 2010. They operated 123 patients in clinical Stages 1-3, 97 of which
      underwent complete resection and systemic lymphadenectomy. RESULTS: A total of 97
      patients (FIGO 2008: Stage 1 in 50 patients, Stage 2 in six, Stage 3 in 37, and
      Stage 4 in four) underwent surgical staging, 74 of which were administered five
      cycles (median) of platinum-based adjuvant chemotherapy. The median overall
      survival (OS) associated with multimodal therapy 50.6 months compared with 34.9
      months incomplete multimodal therapy. After multimodal treatment, 32.9% (32/97)
      patients showed recurrence (24/32 hematogenous). CONCLUSION: Multimodal therapy
      increased survival among uterine CS patients, but the recurrence rate remained
      high. Further consideration of treatment options for uterine CS is required.

PMID- 24020132
TI  - Clinical outcome of patients with microinvasive adenocarcinoma of the uterine
      cervix.
AB  - BACKGROUND: The objective of this analysis was to present the clinical outcome of
      patients with microinvasive adenocarcinoma (AC) of the uterine cervix treated at
      the Department of Obstetrics and Gynecology between 1999 and 2010. MATERIALS AND
      METHODS: The authors analysed 125 patients with microinvasive AC. The analysis
      involved the following parameters: women's age at surgery, type of surgery,
      number of positive lymph nodes, and patient's survival. Additionally, a
      questionnaire regarding history and symptoms before diagnosis and postoperative
      follow-up was developed and analysed specifically for this study. RESULTS: The
      mean women's age at surgery was 40.58 +/- 9.58 years. In 70 women (56%), the
      performed treatment was conization, 34 women (27.2%) underwent simple
      hysterectomy, and 24 (19.2%) women had radical hysterectomy. In 14 (11.2%) women,
      the margins of the cone were not disease-free, in nine of them the authors later
      performed radical hysterectomy. From 14 women who became pregnant after
      treatment, 13 (16.9%) of them gave birth. One of the 125 patients diagnosed with
      microinvasive AC died and the cause of death was rectal carcinoma. CONCLUSION:
      The authors may conclude that conservative management of patients with
      microinvasive AC is safe when exact evaluation of tumor extension and surgical
      margins of the cone are considered, and results in very low risk of recurrence,
      lymph node disease, and death caused by cancer.

PMID- 24020133
TI  - Photodynamic therapy effectively palliates gynecologic malignancies.
AB  - BACKGROUND: There is a need for novel therapies for women with recurrent
      gynecologic malignancies. In this paper, the authors report their experience with
      photodynamic therapy (PDT). PDT involves administering a systemic injection of
      Photofrin II, a selective tumor photosensitizer hematoporphyrin derivative,
      followed by exposure of tumor tissue to visible light at 630 nm. The photodynamic
      destruction of tumor exhibits both cytocidal and vascular effects that may
      contribute to the tumoricidal effects observed. MATERIALS AND METHODS: Patients
      were injected intravenously with two mg/kg Photofrin II. Approximately 48 hours
      post-injection, the tumor was exposed to red light (wavelength 630 nm +/- 2 nm)
      from a laser through a flexible 400-um quartz fiber with an attached microlens to
      produce a spot of uniform intensity and/or diffuser tip fiber to uniformly
      illuminate the cavity. RESULTS: Thirty-two patients with recurrent gynecologic
      malignancies were treated with photodynamic therapy using Photofrin II dye and
      laser. A total of 45 PDT treatments were given; 25 patients received only one
      treatment, five patients received two treatments, two patients received three
      treatments, and one patient received four treatments. There were nine cervical,
      six vulvar, six vaginal, five ovarian, five endometrial carcinomas, and one
      recurrent pagets of the anal canal. Nine out of 11 (82%) patients with metastatic
      cutaneous lesions had a complete response. Five out of 21 patients (24%) with
      vaginal, cervical or anal recurrences had a complete response to therapy with
      median response time of 28 months. Toxicity associated with treatment was limited
      to burning sensation, pain, and edema at treatment site. There were no treatment
      related deaths. CONCLUSIONS: PDT is an effective therapy in patients with
      recurrent gynecologic malignancies and limited treatment options. PDT is an
      alternative therapy that offers the possibility of complete response in select
      groups of patient populations. Specifically, it provides palliation for
      superficial recurrent lesions of skin, cervix, vagina and vulva, in the absence
      of distant disease.

PMID- 24020134
TI  - Development of antiangiogenic therapies for ovarian cancer.
AB  - Angiogenesis is a dynamic process which leads to a development of cancer and
      metastases. The most recognized and dominant prognostic factor is vascular
      endothelial growth factor (VEGF) and its receptors. VEGF was identyfied in 1989.
      There are three receptors for VEGF: VEGFR1 (VEGF receptor 1) and VEGFR2 that play
      the role in angiogenesis and development of ascites, and VEGFR3 is critical for
      lymphangiogenesis. There is bevacizumab--a new drug, monoclonal antibody that can
      block connection VEGF to its receptors. The first notification of activity of
      bevacizumab in ovarian cancer was in 2005. The aim of the article is to show some
      clinical trials in ovarian cancer and their results. The bevacizumab was
      registered in November 2011 in first line with standard chemotherapy in ovarian
      cancer. There is a new weapon against this disease.

PMID- 24020135
TI  - Clinicopathological characteristics and outcome of patients with small cell
      neuroendocrine carcinoma of the uterine cervix: case series and literature
      review.
AB  - OBJECTIVE: To analyze the clinicopathological data of 13 cases of small cell
      neuroendocrine carcinoma (SCNEC) of the uterine cervix who received treatment at
      this medical institutions over the past five years with patient survival as the
      primary endpoint. MATERIALS AND METHODS: The clinicopathologic data of 13 cases
      were reviewed. Immunohistochemistry was performed using antibodies against
      synaptophysin and chromogranin A and Ki-67. Survival was analyzed using the
      Kaplan-Meier method and log-rank tests. RESULTS: The median age of these patients
      was 37 years (range 21-62). Immunohistochemistry showed that the positive rate of
      synaptophysin and chromogranin A was 100% (13/13) and 69.23% (9/13),
      respectively. The median survival of patients with early-Stage I-II SCNEC of the
      uterine cervix (17.5 months) was significantly higher than that of patients with
      advanced stage SCNEC of the uterine cervix (four months) (p < 0.05). There was no
      local recurrence in all 13 patients. Five patients died of distant metastasis in
      less than six months. CONCLUSION: SCNEC of the uterine cervix is a highly
      malignant disease and early-stage patients showed significantly longer survival
      compared to late-stage patients. Early diagnosis and prompt combination treatment
      may improve the outcome of patients with SCNEC of the uterine cervix.

PMID- 24020136
TI  - Epidemiology of HPV-related female cancers in the Umbria region of Italy: pre
      vaccination period.
AB  - The authors describe the incidence and mortality rates of human papillomavirus
      (HPV)-related female cancers in Umbria (Italy) in the pre-vaccination period from
      1978-2008. Joinpoint regression was applied on age-adjusted incidence and
      mortality rates to evaluate temporal trends. Mouth and pharynx cancers incidence
      and mortality trends decreased about three percent per year. For anus and anal
      canal cancer, incidence and mortality trends presented a non-significant
      decrease. For malignant neoplasm of vulva, a significant change was found in
      incidence trend: the annual percentage change decreased from 2001 (- 1.8%).
      Mortality trend showed a non-significant decrease. Incidence and mortality rates
      from vaginal cancer were non-significantly decreased. For malignant neoplasm of
      cervix uteri, incidence rates showed a significant decrease by 2.1% per year.
      Mortality rates decreased as well, although non-significantly. HPV-related
      cancers consistently decreased in Umbria. This trend may be a consequence of
      safer sexual behavior. For cervical cancer, a combination of opportunistic and
      programmed screening led to a much-reduced disease burden. It is expected that
      the implementation of vaccination in the future will lead to a further decrease
      of HPV-related cancer incidence and mortality.

PMID- 24020138
TI  - Role of omentectomy and appendectomy in surgical staging of endometrioid
      endometrial cancer.
AB  - PURPOSE: The purpose of this study was to determine whether it was necessary to
      add omentectomy and appendectomy to the surgical staging of endometrioid
      endometrial cancer. MATERIALS AND METHODS: Records were reviewed from June 2005
      to June 2009 for endometrioid endometrial cancer patients who underwent total
      abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic
      lymphadenectomy, infracolic omentectomy and appendectomy. RESULTS: In total, 186
      patients were included in the analysis. Disease was limited to uterus in 93% of
      patients and 87% of patients had Stage I disease. There was only one omental
      metastasis and no appendix metastasis in all stages. CONCLUSION: Routine
      omentectomy and appendectomy are unnecessary in surgical staging of endometrioid
      endometrial cancer unless there is suspicion of gross metastases during
      intraoperative examination.

PMID- 24020137
TI  - Diagnostic approach and therapeutic management in early-stage endometrial cancer.
AB  - OBJECTIVE: The effectiveness of pelvic and para-aortic lymphadenectomy in the
      morbidity of patients affected by early-stage endometrial carcinoma (EC) is the
      subject of this study. STUDY DESIGN: Ninety-two cases with endometrial cancer
      that underwent para-aortic and pelvic lymphadenectomy, from June 1995 to June
      2006, were studied and compared with 30 cases of patients with endometrial cancer
      without lymphadenectomy. RESULTS: According to the results, systematic pelvic and
      para-aortic lymphadenectomies improved disease-free and overall survival rates
      among the patients with endometrial cancer. The mean number of removed para
      aortic lymph nodes was 19.01 +/- 5.88, whereas the mean number of removed iliac
      lymph nodes was 32.94 +/- 6.69. Forty-two and 31 metastatic iliac and para-aortic
      nodes were found, respectively. No surgery-related deaths and major
      intraoperative injuries occurred. The frequency and the type of postoperative
      complications were not affected by the performance of lymphadenectomy. The
      morbidity rate was 6.2%, similar to the group without lymphadenectomy (5.79%). No
      recurrence occurred in the group with lymphadenectomy, while in the other group
      the recurrence rate was 23.3%. CONCLUSIONS: Lymph nodes metastases can be
      observed in early stages of EC. Pelvic and para-aortic lymphadenectomies seems to
      provide profound information about the Stage of the disease and the patient's
      survival, identifying which patients are suitable for supplementary treatment,
      without significant clinical increase of morbidity.

PMID- 24020139
TI  - Effect of tamoxifen on postmenopausal endometrium.
AB  - PURPOSE: The objective of this study was to evaluate the effect oftamoxifen on
      the endometrium of45 postmenopausal women with breast cancer, as evidenced by
      hysteroscopic, ultrasound, histological methods, and by immunohistochemical
      investigation of the expression of Bcl-2 and Ki67. MATERIALS AND METHODS: Forty
      five postmenopausal women with breast cancer (ER and/or PgR positive) undergoing
      tamoxifen therapy for six to 48 months, were selected from the files of the 2nd
      Department of Obstetrics and Gynecology, University of Athens Aretaieion
      Hospital, among a total of 120 patients treated from 2004-2009. RESULTS: The
      ultrasound findings during the follow-up period revealed 18 cases of thickened
      endometrium, 14 cases of suspected polyps, one case with accumulation of
      endometrial fluid, and 12 cases of heterogeneous endometrial echo texture. The
      patients had undergone hysteroscopy because of thickened endometrium (18/45
      patients), postmenopausal bleeding (14/45 patients), and polyps (13/45 patients).
      The endometrial tissue samples were examined in the Pathology Department of
      Aretaieion Hospital and showed in 23 cases with adenomatous endometrial polyps,
      15 cases with endometrial cystic atrophy, two cases with adenomatous hyperplasia,
      and five cases with mucosal endometrial adhesions. Immunohistochemical
      investigation of Bcl-2 and KJ67 expression was undertaken on paraffin blocks and
      showed elevated expression in the cases with endometrial polyps and hyperplasia,
      in contrast to atrophic endometria. CONCLUSION: Long-term tamoxifen therapy of
      postmenopausal women with breast cancer is associated with uterine pathology.
      Ultrasonography alone is useful in asymptomatic patients selecting cases with
      increased endometrial thickness for further investigation. Hysteroscopy is an
      accurate method for diagnosing endometrial disease because it provides a direct
      view of the uterine cavity, reveals focal lesions, and enables targeted biopsies
      to be performed at the same time. Pathological findings show elevated expression
      of Ki67 and Bcl-2 in hyperplastic endometria and adenomatous polyps, consistent
      with an elevated glandular cell proliferation due to tamoxifen effect.

PMID- 24020140
TI  - The effect of vitamin E on plasmatic malondialdehyde levels during surgical
      removal of ovarian and endometrial carcinomas.
AB  - This study deals with the monitoring of plasmatic levels of malondialdehyde, as
      the main indicator of oxidative damage to biomembranes. Malondialdehyde is
      determined by high-performance liquid chromatography (HPLC) after derivatization
      employing 2,4-dinitrophenylhydrazine. A clinical study involving 20 female
      patients suffering from ovarian and endometrial carcinomas has demonstrated
      elevated levels of malondialdehyde (10.1 +/- 1.1 microM), compared with the
      control group (7.5 +/- 2.7 microM). It has been further verified that surgical
      removal of the tumor leads to an additional increase in the plasmatic
      malondialdehyde content. This unfavourable situation can be effectively
      eliminated by administration of a single dose of vitamin E prior to surgery.

PMID- 24020141
TI  - Embryonal rhabdomyosarcoma of the uterus in a 35-year-old woman: case report and
      review of the literature.
AB  - Embryonal rhabdomyosarcoma (RMS) is a rare sarcoma that characteristically occurs
      in children. The current treatment protocols are based on trials performed in
      patients under 21 years of age. Embryonal RMS in women over 20 years of age is
      rare, and studies on treatments and outcomes are limited. The authors here in
      report a case of a 35-year-old woman with ectocervical RMS who was treated with
      radical hysterectomy followed by chemotherapy. She is currently disease-free.
      Based on a literature review, the authors recommend a surgical approach in
      combination with chemotherapy for treatment of embryonal RMS in adult patients.

PMID- 24020142
TI  - Mesonephric carcinosarcoma of the uterine cervix: a case report.
AB  - Cervical carcinosarcomas are rare neoplasms that aggressively progress and belong
      to the histological group of mixed tumors with both epithelial and mesenchymal
      components (malignant mixed Mullerian tumors). At diagnosis, most patients
      present with vaginal bleeding and a palpable cervical mass. Given the rarity of
      this neoplasm, there is no consensus regarding the management of these patients
      and should be approached on a case-by-case basis, taking into consideration the
      clinical and pathological features of the tumor. The authors describe a woman
      with mesonephric cervical carcinosarcoma and review the literature regarding
      these rare tumors to better understand the natural history of these neoplasms.

PMID- 24020143
TI  - Uterine angiomyolipoma with metastasis in a woman with tuberous sclerosis: a case
      report.
AB  - Extrarenal angiomyolipomas (AMLs) have been reported at various anatomical sites
      such as the liver, spleen, abdominal wall, retroperitoneum, oral cavity, penis,
      spermatic cord, skin, and lung but are infrequently described in gynecological
      regions. However, only a few cases of extrarenal AML in the uterus have been
      reported. The authors describe a case of uterine AML in a 41-year-old woman with
      evidence of tuberous sclerosis. Initial diagnosis concluded with myoma based on
      the interpretation of imaging and other pathological parameters. However, after
      successful laparoscopic surgical staging, AML was diagnosed. To date, the
      feasibility of laparoscopic surgical diagnosis and the risks associated with this
      technique have not been reported. The authors briefly review the implementation
      of laparoscopic surgical staging to diagnose uterine AML.

PMID- 24020144
TI  - Carcinosarcoma of the uterus in advanced stage: a case report.
AB  - This is the case of an advanced stage carcinosarcoma uteri, in a patient with
      limited therapy options. Carcinosarcomas (malignant mixed Mullerian tumors) are
      histologically composed of malignant epithelial and mesenchymal components.
      Sarcomatous component of this mixed tumor in the present patient was of
      heterologous-type chondrosarcoma. The primary treatment option for uterine
      carcinosarcomas is surgery, but adjuvant therapy is always necessary. The optimal
      treatment is still uncertain, as the histogenesis of this tumor remains
      controversial.

PMID- 24020145
TI  - Successful treatment of isolated fibular bone metastasis in a uterine endometrial
      cancer of clear cell carcinoma.
AB  - Clear cell carcinoma of the endometrium is an uncommon histological subtype and
      isolated metastasis to bone is rare. The authors present a case of a 61-year-old
      woman who underwent laparoscopic staging surgery for clear cell carcinoma of
      uterine endometrium (FIGO Stage IB) and early recurrence with isolated fibular
      bone metastasis three months later. With salvage radiotherapy (RT), she remains
      disease-free after 46 months. Curative-intended treatment with RT is possible as
      in this case.

PMID- 24020146
TI  - Endometrial cancer metastasize to the skin of lower leg and vagina: case report
      and literature review.
AB  - Endometrial cancer is the most frequent malignancy of the female reproductive
      system, while cutaneous metastasis is extremely rare in endometrial cancer. The
      authors herein report a case ofendometrial adenocarcinoma (FIGO Stage IIIC2,
      Grade 2) with metastasis to the skin of right lower leg and vaginal orifice. The
      patient was treated with local excision and combination chemotherapy, but she did
      not respond to therapy and died within 11 months. The authors reviewed the
      clinico-pathologic features, treatment, and prognosis of such case with cutaneous
      metastasis.

PMID- 24020147
TI  - Primary signet-ring cell adenocarcinoma of the uterine cervix: case report and
      review of the literature.
AB  - Signet-ring cell adenocarcinoma is a rare subtype of the uterine cervix; thus
      there are no guidelines and the prognosis is unknown. There seems to be a
      significant role for reporting the treatment and outcome of this rare disease in
      order to establish guidelines and to assist in decision-making. However,
      treatment should be tailored to each patient according to clinical status and
      disease stage. Excluding extra-genital origin is mandatory, as it will change
      treatment management considerably.

PMID- 24020148
TI  - Primary squamous cell carcinoma of endometrium: clinicopathologic analysis of two
      cases with review of the literature.
AB  - Two cases of primary squamous cell carcinomas of the endometrium (PSCCE) are
      reported, and both were postmenopausal and presented with vaginal bleeding.
      Histologically, the endometrial curetting revealed extensive squamous metaplastic
      papillae with vacuolated cytoplasms. Numerous keratin debris were present in the
      superficial epithelium with neutrophils infiltration. Atypia existed in the basal
      and parabasal-layer cells. It can be regarded as precancerous lesion when
      postmenopausal woman's endometrial curetting show extensive squamous papillae.

PMID- 24020149
TI  - Transition of low-grade to high-grade endometrial stromal sarcoma: a case report.
AB  - BACKGROUND: The transition of low-grade endometrial stromal sarcoma (ESS) to high
      grade ESS remains a rare clinical event. CASE: A patient presented with abdominal
      pain and abnormal genital bleeding. She underwent a supracervical hysterectomy
      with bilateral salpingo-oophorectomy, omentectomy, and resection of peritoneal
      disseminated lesions. Pathological examination revealed low-grade ESS in the
      uterus and omentum. Immunohistochemical examination showed immunoreactivity for
      CD10 and Ki-67 (MIB1) in the uterus and omentum. However, estrogen receptor,
      progesterone receptor, alpha-SMA, desmin, h-caldesmon, and CAM5-2 were negative.
      P53 immunoreactivity was noted only in the omental lesion. Despite performing six
      courses of adjuvant chemotherapy, she recurred in the abdomen. She underwent
      ileostomy and resection of peritoneal disseminated lesions. Pathology showed high
      grade ESS in the recurrent lesion of the ileum, which was characterized by severe
      cytologic atypia, high mitotic index, multifocal necrosis, increased Ki-67 index,
      and immunoreactivity for p53. CONCLUSION: Although rare, the transition of low
      grade ESS to high-grade ESS may occur and suggests the worsening of the
      prognosis. Pathological examination and immunohistochemistry are useful for the
      diagnosis of the transition of low-grade ESS to high-grade ESS.

PMID- 24020150
TI  - Coexistent gestational choriocarcinoma and mixed adenocarcinoma of the uterus.
AB  - OBJECTIVE: To report the first case of a uterine gestational choriocarcinoma
      coexisting with an endometrial carcinoma (EC) and to discuss its possible
      pathogenesis. MATERIALS AND METHODS: All tissues were examined histologically and
      monoclonal antibodies were used to evaluate the expression of HCG, HPL, P53,
      PTEN, and ER. Genotyping was performed on DNA extracted from the freshly
      dissected choriocarcinoma and the paraffin-embedded endometrial carcinoma along
      with parental blood DNA using multiplex STR-PCR at 16 loci. RESULTS: Histology
      identified two distinct tumors: a uterine tumor containing cytotrophoblastic and
      syncytiotrophoblastic cells and a second distinct neoplasm composed of
      adenocarcinoma resembling endometrioid and mucinous adenocarcinoma. Genotyping of
      the choriocarcinoma revealed alleles from both the patient and her husband and
      was classified as biparental in origin. The endometrial adenocarcinoma contained
      only maternal alleles and was thus classified as maternal in origin. CONCLUSIONS:
      This is the first description of the simultaneous diagnosis of a uterine
      gestational choriocarcinoma and an EC within the same patient. DNA genotyping and
      immunohistochemistry are valuable tools in distinguishing the different origins
      of coexisting tumors.

PMID- 24020151
TI  - A computerized procedure for teaching the relationship between graphic symbols
      and their referents.
AB  - Many individuals with little or no functional speech communicate through graphic
      symbols. Communication is enhanced when the relationship between symbols and
      their referents are learned to such a degree that retrieval is effortless,
      resulting in fluent communication. Developing fluency is a time consuming
      endeavor for special educators and speech-language pathologists (SLPs). It would
      be beneficial for these professionals to have an automated procedure based on the
      most efficacious method for teaching the relationship between symbols and
      referent. Hence, this study investigated whether a procedure based on the
      generation effect would promote learning the association between symbols and
      their referents. Results show that referent generation produces the best long
      term retention of this relationship. These findings provide evidence that
      software based on referent generation would provide special educators and SLPs
      with an efficacious automated procedure, requiring minimal direct supervision, to
      facilitate symbol/referent learning and the development of communicative fluency.

PMID- 24020152
TI  - Smart grab bars: a potential initiative to encourage bath grab bar use in
      community dwelling older adults.
AB  - Grab bars are often prescribed to ensure safe and independent bathing and
      toileting. Studies have shown that seniors do not always use grab bars when they
      are present or are reluctant to install them due to the associated stigma. This
      study sought to determine if artificial intelligence could increase grab bar use
      by seniors and to determine the efficacy of different cues (auditory, visual, and
      audiovisual combination) on the frequency of use of a grab bar. Sixty-nine
      healthy participants aged 60 to 86 years (average 68.7 years) were randomly
      assigned to three subgroups. Each subgroup tested two different cueing
      conditions: the no cue and one of three cued conditions (visual, auditory, or
      combined audio-visual). Results suggest that the smart grab increased seniors'
      grab bars use by 39% and that the effect was maintained after removal of the
      cues. Participants preferred the visual cue but the auditory cue was the most
      powerful. Results suggest that artificial intelligence may be an interesting
      avenue to increase grab bar use in community-dwelling older adults and in people
      requiring supervision to use grab bars on a regular basis to decrease the risk of
      falls during bathing or bathtub transfers.

PMID- 24020153
TI  - Effects of a self-monitoring device on socially relevant behaviors in adolescents
      with Asperger disorder: a pilot study.
AB  - This article reports the results of two case studies. Two middle school-aged
      participants with high-functioning autism spectrum disorders were taught to self
      monitor behaviors impacting their social acceptance by peers in their general
      education settings: oral self-stimulatory behaviors and conversation skills.
      Results indicate that the intervention was effective to some degree with both
      participants. As a result of the self-monitoring intervention, one participant
      decreased self-stimulatory behaviors; however, his data were highly variable
      throughout the study though lower on average during intervention than in
      baseline. The other participant's targeted skills in communication were only
      slightly improved. Self-monitoring using a vibrating reminder appears to be a low
      cost intervention with high levels of social acceptability, low training
      requirements for teachers or students, and no social stigma.

PMID- 24020154
TI  - Resource consumption and simulator driving performance using adaptive controls.
AB  - This research seeks to understand the usability of portable assistive driving
      devices as it relates to driver performance and safety. Through the use of a
      computer-based simulation, two sets of hand controls were tested in an
      environment containing driving hazards. Ten participants drove an ambulance
      through two sessions of high-demand, hazardous scenarios in a computer-based
      driving simulator. Participants drove one session with each of the two available
      portable hand control devices. From each of these driving sessions, driving
      performance metrics were measured in the form of time-to-complete, number of
      damage-inflicting collisions, percentage of vehicle damage accrued by the end of
      the drive, and percentage of road course completed. Data were also collected from
      a posttest survey about which hand control device participants preferred using.
      Results demonstrated no significant differences between hand control devices with
      regard to course completion, amount of damage sustained to vehicle, or number of
      collisions. However, a trend was identified for preference of hand control based
      on experience, regardless of driving performance. Although the objective results
      of this study were not significant, the study leads to interesting avenues of
      future research regarding preference as well as the need for larger populations
      of individuals with disabilities in simulation studies.

PMID- 24020155
TI  - Spelling on the fly: investigating a pentop computer to improve the spelling
      skills of three elementary students with disabilities.
AB  - The purpose of this study was to examine the effects of a pentop computer and
      accompanying spelling software on the spelling accuracy and academic engagement
      behavior in three elementary students with disabilities who were served in a
      resource room setting. Using a multiple baseline across students single subject
      research design, researchers determined student use of the pentop computer--the
      FLYPen--and its spelling software may serve as an equivalent intervention to
      traditional spelling instruction. While academic engagement performance increased
      considerably for students when using the FLYPen, results indicated little to no
      improvement over traditional instruction in spelling accuracy. Implications and
      suggestions for future research are presented.

PMID- 24020156
TI  - Visual inspections of wheelchair cushions after everyday use.
AB  - The objective of this project was to document the state of wheelchair cushions
      after everyday use by identifying signs of wear, fatigue, and failure. Visual
      inspection was done on 202 wheelchair cushions with average and median ages of
      2.7 and 2 years, respectively. Most cushions were deemed to be "clean" and the
      proportion did not change across age groups. A high proportion of cushion covers
      showed signs of wear with damage to fabric and seams being most prevalent. Foam
      cushions showed more signs of wear than viscous fluid or air cushions. More than
      60% of foam cushions showed signs of permanent deformation, and in nearly half,
      the foam exhibited granulation or brittleness. About 15% of the bladders used in
      viscous fluid or air cushions exhibited cracks or breaks in the material. In
      conclusion, a visual inspection of wheelchair cushions showed that most cushions
      appeared clean and were in good repair over a wide range of ages and usage
      patterns. While documenting signs of wear after use can help inform interventions
      and monitoring, research is needed to document changes in performance of
      wheelchair cushions overtime as a means to develop better replacement strategies.

PMID- 24020157
TI  - Don't be a wallflower.

PMID- 24020158
TI  - Health care's 'best hope'.

PMID- 24020159
TI  - A trustee at 24?

PMID- 24020160
TI  - Engaging hospital workers.

PMID- 24020161
TI  - Forget your ego and listen.

PMID- 24020162
TI  - Retraining clinicians, step 1.

PMID- 24020163
TI  - Quality control: Doctors lobby for adaptable quality measures.

PMID- 24020164
TI  - X-ray vision: Getting a clearer picture on imaging management.

PMID- 24020165
TI  - RECs complete: End of the road for IT help centers?

PMID- 24020166
TI  - Germ killer: How clean is clean?

PMID- 24020167
TI  - Telemonitoring vulnerable patients in their homes.

PMID- 24020168
TI  - An eye on the OR: New York health system tries cameras to boost checklist
      compliance.

PMID- 24020169
TI  - Walking the talk: Designed for top performance.

PMID- 24020170
TI  - Stars of the field. The AHA Awards issue.
AB  - Our second annual awards issue puts a much-deserved spotlight on health care
      organizations that have spearheaded creative and highly successful initiatives to
      improve the health of their communities. They provide important examples for
      others to learn from and adapt to the needs of their own populations. Once again,
      we applaud them all.

PMID- 24020171
TI  - The AHA-McKesson Quest for Quality Prize.

PMID- 24020172
TI  - The AHA NOVA Award.

PMID- 24020173
TI  - The Circle of Life Award.

PMID- 24020174
TI  - The Dick Davidson Quality Milestone Award.

PMID- 24020175
TI  - The Most Wired Innovator Award.

PMID- 24020176
TI  - Hospital operations management: improving organizational efficiency.
AB  - Reducing operational inefficiencies represents one of the most promising sources
      of potential savings in hospitals today. Health Forum convened a panel of
      hospital executives and industry experts to discuss the daunting challenges and
      big opportunities that lie ahead.

PMID- 24020177
TI  - [Morpho-functional changes of the pyramidal neurons in various hippocampal areas
      after the ischemic postconditioning].
AB  - The aim of this study was to determine the effect of ischemic postconditioning
      (IP) on the viability of neurons in various hippocampal areas as well as on
      cytoplasmic activity of succinatedehydrogenase (SDH) in these cells in 30 male
      Mongolian gerbils (Meriones unguiculatus). Ischemic brain injury was induced by
      bilateral common carotid artery occlusion for 7 min. IP protocol comprised 3
      cycles of 15 s of reperfusion/15 s of ischemia. After reperfusion for 48 h, the
      morphometric analysis was conducted, and SDH cytoplasmic activity was assessed
      using quantitative histochemistry in the pyramidal neurons of the hippocampal
      areas CA1, CA2, CA3, CA4. The experiment has demonstrated that 7-minute-long
      ischemia resulted in a significant decrease in the number of viable neurons in
      CA1 area (up to 24%) and in the CA3 (to 56%) of the hippocampus; besides, it lead
      to the elevation of SDH activity in the cytoplasm of the neurons in all the
      hippocampal areas as compared to that in sham-operated animals. The application
      of IP significantly increased the number of viable neurons in CA1 (up to 52.9%,
      P<0,01) and in CA3 areas of the hippocampus(up to 88%, P<0,05), and it was
      accompanied by reduction of SDH activity in surviving neurons in all the
      hippocampal areas.

PMID- 24020178
TI  - [Reactive changes of the rat brain cellular elements under different conditions
      of circulatory hypoxia].
AB  - The aim of this study was to detect structural, spatial and quantitative changes
      of cellular elements of midbrain paranigral nucleus (PNN) and telencephalic
      anterior cingulate area (ACA) under different conditions of circulatory hypoxia.
      PNN anteriormedial part and ACA layers V-VI were examined in adult rats 7 days
      (n=4) after an occlusion of both common carotid arteries as well as in intact
      (1st control, n=4) and sham-operated animals (2nd control, n=4). In histological
      the sections, stained with Nissl cresyl violet, and using the methods of glial
      fibrillary acidic protein and an Ibal-protein detection, the proportions of
      unmodified, hypochromic, pyknomorphic neurons and ghost cells were determined as
      well as the numbers of astrocytes, oligodendrocytes, microgliocytes and
      endotheliocytes. Cell body area of neurons and gliocytes, and the distance
      between cell bodies and capillaries were measured, a gliocyte-neuronal index was
      calculated. It was found that brain cellular elements that survive different
      conditions of a circulatory hypoxia underwent a range of pathological changes.
      Neurons were in process of nuclear pyknosis, lysis and transformation into the
      ghost cells. The cells within the hypoxia nuclear zone were prone to death or
      pyknosis. The neurons located outside the area of hypoxia which were affected
      only by a humoral impact of reactions of the glutamate-calcium cascade,
      frequently underwent acute swelling. Microgliocyte reaction in the form of poorly
      expressed increase in their number and structural signs of activation was an
      early diffuse manifestation of a prosencephalic focal hypoxia. Endotheliocyte
      proliferation 7 days after of ischemic challenge was not associated with a chain
      of cascade reactions and was observed only in the hypoxia focus. Concentration of
      viable neurons and astrocytes near blood capillaries, as well as an increase in
      the number of satellite form gliocytes is an adaptation mechanism and a condition
      for the survival of cells during various types of brain exposure to ischemia.

PMID- 24020179
TI  - [The organization of the projections of the rostromedial tegmental nucleus to the
      striatum in canine brain].
AB  - Method of retrograde axonal transport of horseradish peroxidase and fluorochromes
      was used to study the organization of the projections of the rostromedial
      tegmental nucleus (RMTN) to the functionally diverse regions of striatal
      structures of dog brain (n=26). It was found that the projection fibers of the
      neurons of RMTN limbic medial part were directed only to the ventral limbic
      segments of the nucleus caudatus, the putamen and the nucleus accumbens. However,
      the convergence of the projection fibers originating from the neurons of
      functionally different RMTN parts was observed in the majority of the segments of
      the striatal structures. Thus, the projection fibers of the motor lateral and the
      limbic medial RMTN parts were directed to the motor dorso-lateral segment of the
      caudate nucleus and also to the striatal segments, which were innervated by the
      fibers from the neurons of functionally diverse structures (ventro-lateral
      segment of the caudate nucleus and the lateral segment of the nucleus accumbens).
      Possible pathways conducting functionally different information and its
      integration in the investigated projection systems are discussed.

PMID- 24020181
TI  - [Cellular composition of diffuse lymphoid tissue in the mucous membrane of human
      larynx under conditions of physiological norm and in fatal hypothermia in the
      Republic of Sakha (Yakutia)].
AB  - Using histological, morphometric and immunnohistochemical methods, cellular
      composition and cytoarchitectonics of diffuse lymphoid tissue in the mucous
      membrane of the larynx was studied in 29 men aged 17-74 years, who died from
      general body hypothermia in the winter period and in 27 men who died from
      mechanical injury during the summer. Significant changes in the cellular
      composition of diffuse lymphoid tissue of the mucous membrane in the various
      parts of the larynx were detected in fatal hypothermia, which included the
      decrease in the number of T-, B-lymphocytes and plasma cells and the increase in
      the number of macrophages in all age groups, indicating the suppression of local
      immunity in persons who died due to the action of low temperature.

PMID- 24020180
TI  - [Morpho-functional characteristics of human spleen (an immunohistochemical
      study)].
AB  - Using immunohistochemical and morphometric methods, the quantitative composition
      and structural localization of immunocompetent cells were studied in human spleen
      (n=20, autopsy material). The detailed morpho-functional characteristics of
      splenic white and red pulp are presented. Cell subpopulations of T (CD3+, CD4+,
      CD8+) and B lymphocytes (CD20+), natural killer cells (CD57+), tissue macrophages
      (CD68+) and dendritic cells (CD35+, S100+) were studied. An analysis of the
      correlations of immunocompetent cells in different regions of white and red pulp
      may become the basis for optimization of histopathological diagnosis definition
      in clinical practice

PMID- 24020182
TI  - [Morphological peculiarities of peripheral blood lymphocytes in arctic foxes
      after administration of various doses of vitamins A and E].
AB  - The aim of this work was to study the effect of various doses of vitamins A and E
      on the morphometric parameters and surface architectonics peculiarities of
      peripheral blood lymphocytes in veiled Arctic foxes. Using light microscopy, it
      was found that in the blood of veiled Arctic foxes (n=30) most of the lymphocytes
      had relatively smooth surface, and only in some cells cytoplasmic protrusions
      were observed. Large doses of vitamins A and E that were introduced into animal
      diet, caused significant reduction of morphometric parameters in relatively
      smooth forms of lymphocytes, while vitamin A changed the microrelief of their
      surface.

PMID- 24020183
TI  - [Age peculiarities of the muscle regeneration after injury, exposure to he-ne
      laser and alloplasty with muscle tissue from the animal of the same age].
AB  - The recovery of the injured muscles were studied in young (aged 1 month), adult
      (aged 3-4 months) and old (aged 24-30 months) outbred male rats (24 animals in
      each group) after alloplasty of the injured area with the muscle tissue taken
      from the animal of the same age under the conditions of implantation of muscle
      tissue, non-irradiated by laser, into the area of injury of the muscle irradiated
      by laser (1st series) and vice versa, implantation of the muscle tissue
      irradiated by laser, into the area of injured non-irradiated muscle (2nd series).
      It is shown that in each age group in the 1st and the 2nd series, the allogeneic
      muscle tissue is is capable of regeneration. The regenerate mass s and the
      proportion of muscle tissue in them tended to be greater in the animals in the 1
      series, as compared to those in the 2nd series. Alloplasty with the muscle tissue
      of the animal of the same age was more effective in young rats than in the old
      ones.

PMID- 24020184
TI  - [Somatotypological and regional regularities of ultrasound anatomy of the thyroid
      gland].
AB  - The purpose of this study was to establish the regularities of the anatomical
      structure of the thyroid gland (TG) in healthy people aged 17-30 years of various
      somatic types, living in the Rostov region. The complex study of TG was carried
      out in 306 healthy subjects (150 male and 156 female) with ultrasonography
      performed according to C. L. Brown (1981). Somatotyping was done using the
      technique of R. N. Dorokhov and V. G. Petrukhina (1989). Sexual dimorphism of the
      linear dimensions, right and left lobe volumes and of TG total volume was
      demonstrated. In men,TG total volume was significantly greater (P<0.05), than
      that in women (11.7 +/- 0.43 and 9.37 +/- 0.28 cm3, respectively). Regional and
      constitutional features of the thyroid gland in healthy subjects living in the
      Rostov region were established. Linear dimensions, total TG volume and the
      volumes of TG lobes were found to be lower in the residents of the Rostov region
      as compared to these parameters in people living in the northern regions of
      Russia.

PMID- 24020185
TI  - [Structural organization of the duodenal wall and its lymphoid tissue in the
      persons of elderly age].
AB  - Structural organization of the duodenal wall was studied in older men (aged 70-75
      years, n=15), and its lymphoid tissue was examined using the qualitative and
      quantitative analysis. Deformation, flattening and sparseness of the intestinal
      villi were identified. Atrophic phenomena in the organ mucous membrane were
      accompanied by the destruction of the cells of surface epithelium, crypts and
      glands. Simultaneous infiltration of the lamina propria with lymphocytes,
      eosinophils, neutrophils and malfunctions in a microcirculatory bed is indicative
      of the presence of inflammatory processes. The duodenum of the elderly persons
      was characterized by the disruption of the integrity of the lamina muscularis
      mucosae that lead to the displacement of the duodenal glands from submucosa to
      the lamina propria. The suppression of cell proliferative activity, decreased
      blast transformation activity, in the lymphoid tissue of the intestine, along
      with a high degree of cell destruction, lead to the weakening of local immunity
      in the elderly persons.

PMID- 24020186
TI  - [Tissue reactions during the degradation of polylactide implants in the body].
AB  - Tissue reactions, accompanying the degradation processes of polylactide (PLA)
      implants after their placement into the subcutaneous tissue, were studied by the
      methods of light microscopy in 6 month-old Wag rats (n=24) weighing 180-200 g. It
      was found that PLA implants became encapsulated by connective tissue. If the
      implant or its fragment had sharp margins that damaged the tissues, a thick
      capsule was formed with a distinct inflammatory infiltration and the sclerosis of
      the surrounding tissues. If the implant had no sharp margins, the capsule was
      thin, and the activity of inflammation was minimal. In all cases, the giant cells
      of foreign body type were present in the capsule and next to it. Gradually,
      during 6 months, the activity of inflammatory process subsided. Inflammation
      sharply increased 12 months after the implantation, when, as a result of effect
      of enzymes released by phagocytes and deformation by a capsule, PLA implants were
      either fragmented or is liquified. PLA-based materials are not totally
      biodegradable, and may persist in the body for a long time.

PMID- 24020187
TI  - [Changes in the knee joint synovial membrane and articular cartilage during shin
      lengthening by autodistractor at increased daily rate].
AB  - Light microscopy and computerized morpho- and stereometry were used to examine
      the changes in the knee joint articular cartilage and synovial membrane studied
      during experimental canine shin lengthening by 15% of initial length by
      autodistraction at increased rate - 3 mm per day with switching on the automatic
      device 120 times. By the end of distraction period (10 days) the destructive
      changes in articular cartilage were more marked in the superficial and deep
      zones, synovitis of moderate and mild degree was observed accompanied by the
      destructive changes in the blood vessels and nerves of the subsynovial layer.
      Regeneration of articular cartilage was incomplete, and regressive neurovascular
      changes persisted in synovial membrane 30 days after the device removal.
      Comparison of these results with the previous data obtained using the distraction
      rate of 3 mm applied 180 times, leads to the conclusion, significant for
      functional prognosis, of the worsening the parameters of structural cartilage
      recovery in case of distraction pitch increase from 0.017 mm to 0.025 mm.

PMID- 24020188
TI  - [Extraependymal ependymocytes in the rat brain].
AB  - The aim of the study was to test the hypothesis on the presence, in intact rat
      brain, of the cells located outside the ependymal layer, but possessing the
      structural organization and cytochemical characteristics similar to those of
      ependymocytes. The study was carried out on Wistar rats (n=10). Ependymocytes
      were identified using immunocytochemical reactions to ezrin and vimentin and were
      visualized with light and confocal microscopy. Cells, structurally and
      cytochemically similar to typical ependymocytes, were found outside the layer of
      ependymocytes in the nervous tissue of intact rat brain. It is suggested that
      extraependymal ependymocytes may have a function of reserve population of the
      neural stem cells in the brain.

PMID- 24020189
TI  - [Vimentin and S100 protein in the developing rat dorsal root ganglion cells].
AB  - The aim of this research was to study the expression of vimentin, one of the
      intermediate filament proteins, and S100 protein in the cells of developing
      dorsal root ganglion in prenatal ontogenesis in Wistar rat embryos (n=22) on 12
      19 days of development and in newborn rats (n=6). Immunohistochemical staining
      methods were used to study the formation of rat dorsal root ganglion glial cells.
      Vimentin-immunopositive neural and glial progenitor cells were present in dorsal
      root ganglion primordia in rat embryos at 12-17 prenatal days. At the later
      stages (day 19 of prenatal life and day 1 of postnatal life) vimentin was found
      to be synthesized only by the differentiating glial cells. It was shown that at
      the same time, S100 protein was first detected in the glial cells of rat dorsal
      root ganglion. On postnatal day 1, the tendency was noted for the accumulation of
      S100 protein in the larger neurons, that was characteristic to mature dorsal root
      ganglia.

PMID- 24020190
TI  - [Application of the immunohistochemical detection of PGP 9.5 protein for the
      study of rat and human heart innervation].
AB  - In this paper we describe the modern immunohistochemical method detecting the
      neuronal marker PGP 9.5. The application of this method for the study of the
      innervation of rat and human heart, the detailed examination of the topography of
      the cardiac nervous apparatus, as well as their changes in pathological states,
      is demonstrated. Structural organization and the nature of the terminal branches
      of nerve apparatus suggest that they have afferent function. Protocol of the
      reaction demonstrating PGP 9.5 on paraffin sections is presented.

PMID- 24020191
TI  - [Teaching histology, cytology and embryology under conditions of higher school
      reform].

PMID- 24020192
TI  - [Experience of human anatomy teaching in West-Kazakhstan Ospanov Medical
      University].

PMID- 24020193
TI  - [The creator of Russian anatomical and medical terminology (to 300th anniversary
      of birth)].

PMID- 24020194
TI  - The three pillars of photo-initiated quantum molecular dynamics.
AB  - Studies of the interaction of light with matter, based on spectroscopy and
      diffraction, yielded a microscopic view of nature. The detailed structure of
      molecules and solids emerged from this effort and led to many of the advances of
      the 20th century, with the 'structure-function' paradigm being perhaps paramount.
      This static view of Nature is a necessary but insufficient advance and, in the
      21st century, we will need to develop microscopic yet dynamical views of Nature.
      We consider here issues in Photo-initiated Quantum Molecular Dynamics raised by
      Faraday Discussions 163, in the context of three main categories or 'pillars' of
      light-matter interaction: energy/time, phase/ coherence, intensity.

PMID- 24020195
TI  - A new approach toward transition state spectroscopy.
AB  - Chirped-Pulse millimetre-Wave (CPmmW) rotational spectroscopy provides a new
      class of information about photolysis transition state(s). Measured intensities
      in rotational spectra determine species-isomer-vibrational populations, provided
      that the rotational populations can be thermalized. The formation and detection
      of S(0) vinylidene is discussed in the limits of low and high initial rotational
      excitation. CPmmW spectra of 193 nm photolysis of vinyl cyanide (acrylonitrile)
      contain J = 0-1 transitions in more than 20 vibrational levels of HCN and HNC,
      but no transitions in vinylidene or highly excited local-bender vibrational
      levels of acetylene. Reasons for the non-observation of the vinylidene co-product
      of HCN are discussed.

PMID- 24020196
TI  - Time-resolved photoelectron imaging of the iodide-thymine and iodide-uracil
      binary cluster systems.
AB  - The energetics and dynamics of thymine and uracil transient negative ions were
      examined using femtosecond time-resolved photoelectron imaging. The vertical
      detachment energies (VDEs) of these systems were found to be 4.05 eV and 4.11 eV
      for iodide-thymine (I(-) x T) and iodide-uracil (I(-) x U) clusters,
      respectively. An ultraviolet pump pulse was used to promote intracluster charge
      transfer from iodide to the nucleobase. Subsequent electron detachment using an
      infrared probe pulse monitored the dynamics of the resulting transient negative
      ion. Photoelectron spectra reveal two primary features: a near-zero electron
      kinetic energy signal attributed to autodetachment and a transient feature
      representing photodetachment from the excited anion state. The transient state
      exhibits biexponential decay in both thymine and uracil complexes with short and
      long decay time constants ranging from 150-600 fs and 1-50 ps, respectively,
      depending on the excitation energy. However, both time constants are
      systematically shorter for I(-) x T. Vibrational autodetachment and iodine loss
      are identified as the primary decay mechanisms of the transient negative ions of
      thymine and uracil.

PMID- 24020197
TI  - A multi-sheeted three-dimensional potential-energy surface for the H-atom
      photodissociation of phenol.
AB  - Extending the previous work of Lan et al. [J. Chem. Phys., 122, 224315 (2005)], a
      multi-state potential model for the H atom photodissociation is presented. All
      three "disappearing coordinates" of the departing H atom have been considered. Ab
      initio CASSCF computations have been carried out for the linear COH geometry of
      C(2v) symmetry, and for several COH angles with the OH group in the ring plane
      and also perpendicular to the ring plane. By keeping the C6H5O fragment frozen in
      a C(2v)-constrained geometry throughout, we have been able to apply symmetry
      based simplifications in the constructions of adiabatic model. This model is able
      to capture the overall trends of twelve adiabats at both torsional limits for a
      wide range of COH bend angles.

PMID- 24020198
TI  - Probing ultrafast dynamics in photoexcited pyrrole: timescales for pi sigma*
      mediated H-atom elimination.
AB  - The heteroaromatic ultraviolet chromophore pyrrole is found as a subunit in a
      number of important biomolecules: it is present in heme, the non-protein
      component of hemoglobin, and in the amino acid tryptophan. To date there have
      been several experimental studies, in both the time- and frequency-domains, which
      have interrogated the excited state dynamics of pyrrole. In this work, we
      specifically aim to unravel any differences in the H-atom elimination dynamics
      from pyrrole across an excitation wavelength range of 250-200 nm, which
      encompasses: (i) direct excitation to the (formally electric dipole forbidden)
      1(1)pisigma* (1A2) state; and (ii) initial photoexcitation to the higher energy 1
      pipi* (1B2) state. This is achieved by using a combination of ultrafast time
      resolved ion yield and time-resolved velocity map ion imaging techniques in the
      gas phase. Following direct excitation to 1(1)pisigma* (1A2) at 250 nm, we
      observe a single time-constant of 126 +/- 28 fs for N-H bond fission. We assign
      this to tunnelling out of the quasi-bound 3s Rydberg component of the
      1(1)pisigma* (1A2) surface in the vertical Franck-Condon region, followed by non
      adiabatic coupling through a 1(1)pisigma*/S(0) conical intersection to yield
      pyrrolyl radicals in their electronic ground state (C4H4N(X)) together with H
      atoms. At 238 nm, direct excitation to, and N-H dissociation along, the
      1(1)pisigma* (1A2) surface is observed to occur with a time-constant of 46 +/- 22
      fs. Upon initial population of the 1pipi* (1B2) state at 200 nm, a rapid 1pipi*
      (1B2) --> 1(1)pisigma* (1A2) --> N-H fission process takes place within 52 +/- 12
      fs. In addition to ultrafast N-H bond cleavage at 200 nm, we also observe the
      onset of statistical unimolecular H-atom elimination from vibrationally hot S(0)
      ground state species, formed after the relaxation of excited electronic states,
      with a time-constant of 1.0 +/- 0.4 ns. Analogous measurements on pyrrole-d1
      reveal that these statistical H-atoms are released only through C-H bond
      cleavage.

PMID- 24020200
TI  - Electronic transient spectroscopy from the deep UV to the NIR: unambiguous
      disentanglement of complex processes.
AB  - Complex multi-stage relaxation and reaction pathways after the optical excitation
      of molecules makes the disentanglement of the underlying mechanisms challenging.
      We present four examples that a new transient spectrometer with excitation fully
      tunable from the deep UV to the IR and 225 to 1700 nm probing allows for an
      analysis with greatly reduced ambiguity. The temporal resolution of about 50 fs
      allows us to resolve all relevant processes. For each example there is a new
      twist in the sequence of relaxation steps that had previously been overlooked. In
      malachite green it appears that the importance of the phenyl twisting has been
      overemphasized and rather a charge transfer state should be considered. In
      TINUVIN-P the predicted twisting as the driving motion for the ultrafast IC is
      confirmed and leads to a resolution of the earlier puzzle that the sub-5 ps
      regime shows kinetics deviating from a pure cooling process despite the sub-ps
      proton transfer cycle. For the bond cleavage of Ph2CH-Cl and Ph2CH-Br the degree
      of electron transfer within the radical pair can now be determined quantitatively
      and leads to a profound understanding of the long-term cation yield. For the
      first time coherent wavepacket motion in the photoproducts is reported. Last but
      not least the measurement of the GSB recovery in the deep UV allows for the
      surprising result, that even after S2 excitation of cyclopentenones the triplet
      states are reached with near unity probability within a few picoseconds.

PMID- 24020201
TI  - Ultrafast ring-opening reactions: a comparison of alpha-terpinene, alpha
      phellandrene, and 7-dehydrocholesterol with 1,3-cyclohexadiene.
AB  - The excited and ground state dynamics of a series of 1,3-cyclohexadiene
      derivatives and their hexatriene photoproducts are studied using ultrafast
      broadband UV-visible transient absorption spectroscopy. The substitution pattern
      around the cyclohexadiene backbone alters the excited state potential energy
      surface in the Franck-Condon region as evidenced by changes in the excited state
      absorption and fluorescence properties of the systems. Unsubstituted 1,3
      cyclohexadiene and alpha-phellandrene exhibit no excited state absorption while a
      strong excited state absorption in the visible spectral region is observed for
      both alpha-terpinene and Provitamin D3. Steric factors introduced by the ring
      substitutions determine the dominant rotational isomer at equilibrium for the
      hexatriene photoproducts. Coupling to the solvent during the conformational
      relaxation from the initial helical all-cis hexatriene is unique to each
      photoproduct, but the relaxation process occurs on a 6-10 ps timescale regardless
      of the size or substitution pattern on the triene.

PMID- 24020202
TI  - Ultrafast photo-initiated molecular quantum dynamics in the DNA dinucleotide
      d(ApG) revealed by broadband transient absorption spectroscopy.
AB  - The ultrafast photo-initiated quantum dynamics of the adenine-guanine
      dinucleotide d(ApG) in aqueous solution (pH 7) has been studied by femtosecond
      time-resolved spectroscopy after excitation at lambda = 260 nm. The results
      reveal a hierarchy of processes on time scales from tau < 100 fs to tau > 100 ps.
      Characteristic spectro-temporal signatures are observed indicating the
      transformation of the molecules in the electronic relaxation from the photo
      excited state to a long-lived exciplex. In particular, broadband UV/VIS excited
      state absorption (ESA) measurements detected a distinctive absorption by the
      excited dinucleotide around lambda = 335 nm, approximately 0.5 eV to the blue
      compared to the maximum of the broad and unstructured ESA spectrum after
      excitation of an equimolar mixture of the mononucleotides dAMP and dGMP. A
      similar feature has been identified as signature of the excimer in the dynamics
      of the adenine dinucleotide d(ApA). The lifetime of the d(ApG) exciplex was found
      to be tau = 124 +/- 4 ps both from the ESA decay time and from the ground-state
      recovery time, far longer than the sub-picosecond lifetimes of excited dAMP or
      dGMP. Fluorescence-time profiles measured by the up-conversion technique indicate
      that the exciplex state is reached around approximately 6 ps after excitation.
      Very weak residual fluorescence at longer times red-shifted to the emission from
      the photo-excited state shows that the exciplex is almost optically dark, but
      still has enough oscillator strength to give rise to the dual fluorescence of the
      dinucleotide in the static fluorescence spectrum.

PMID- 24020204
TI  - Coherent exciton transport driven by torsional dynamics: a quantum dynamical
      study of phenylene-vinylene type conjugated systems.
AB  - We present a quantum dynamical study of exciton transfer across a torsional
      defect that locally breaks the pi-conjugation in an oligo-(p-phenylene vinylene)
      (OPV) fragment. A site-based vibronic coupling Hamiltonian is used which is
      formulated in a comparative fashion (i) for a Frenkel exciton basis, assuming
      localized electron-hole pairs whose superposition yields a delocalized exciton,
      and (ii) more accurately, for a Merrifield type exciton basis including spatially
      separated electron-hole pairs. Starting from a partially delocalized
      ("spectroscopic unit") initial condition, the observed transfer dynamics is found
      to involve two characteristic time scales: (i) a very rapid, coherent transient
      on a 10-100 femtosecond scale, largely determined by Rabi type oscillations
      modulated by bond-length-alternation modes, and (ii) a slower time scale
      involving the planarization of the torsional coordinates that determines the
      onset of a quasi-stationary exciton-polaron state, and in the process leads to a
      "healing" of the torsional defect within - 500 femtoseconds. The dynamics
      obtained from the full electron-hole basis vs. Frenkel basis are in good
      agreement. In the full electron-hole dynamics, the transients are found to
      involve a rapid expansion and subsequent contraction of the electron-hole
      coherence size. Quantum dynamical simulations for a minimal six-site model
      involving 36 states and 22 vibrational modes, were carried out using the
      multiconfiguration time dependent Hartree (MCTDH) method.

PMID- 24020203
TI  - Photodynamics of Lys+-Trp protein motifs: hydrogen bonds ensure photostability.
AB  - Cation-pi interactions such as Lys(+)-Trp, are highly abundant structural motifs
      in proteins. Both, experimental and theoretical studies of small prototypical gas
      phase systems, H+Trp, H+Trp x (H2O)n and H+Gly-Trp, indicate such an arrangement
      as potential hot spot for photodamage and photoinstability. Here, we study the
      photodynamical properties of a Lys(+)-Trp pair in the protein human serum albumin
      (HSA) using nonadiabatic mixed time-dependent density functional theory/molecular
      mechanics simulations (TDDFT/MM). These simulations show that the findings for
      small protonated Trp complexes are largely transferable to a more complex protein
      environment. Under partially hydrated ("dry" conditions), when the -NH3+ head
      group is not fully solvated, photoexcitation of the tryptophan leads indeed to
      rapid photodissociation of the proximal charged amino group. In contrast,
      photostability is well maintained under fully solvated conditions when the lysine
      head group is fully hydrogen-bonded. In this case, photodynamics takes place in a
      pi-pi* state without interference of fast dissociative sigma*C-N) or sigma*N-H
      channels. These results highlight the crucial role of hydrogen bonds in ensuring
      the photostability of essential biological building blocks.

PMID- 24020205
TI  - Quantum-classical effective-modes dynamics of the pipi* --> npi* decay in 9H
      adenine. A quadratic vibronic coupling model.
AB  - We present mixed quantum-classical simulation of the internal conversion between
      the lowest energy pipi* (S(La)) and npi* (S(n)) excited electronic states in
      adenine in the gas phase, adopting a quadratic vibronic model (QVC), parametrized
      with the help of PBE0 density functional calculations. Our approach is based on a
      hierarchical representation of the QVC Hamiltonian and a subsequent treatment of
      the most relevant coordinates at accurate time-dependent quantum level and of the
      other 'bath' modes at classical level. We predict an ultrafast transfer (-30 fs)
      of approximately 75% of the initial population excited on S(La) to S(n). Within
      an adiabatic picture, on the same timescale the wave packet concentrates almost
      completely on the lowest S1 state, where however it shows a very broad
      distribution with different characteristics (due to the different 'diabatic'
      character). It is shown that the proposed methodology offers a practicable route
      to describe the quantum dynamics of internal conversion processes in large semi
      rigid systems.

PMID- 24020207
TI  - Ultrafast excited state dynamics of the green fluorescent protein chromophore and
      its kindling fluorescent protein analogue.
AB  - Fluorescent proteins exhibit a very diverse range of photochemical behaviour,
      from efficient fluorescence through photochromism to photochemical reactivity.
      Remarkably this diverse behaviour arises from chromophores which have very
      similar structures. Here we describe measurements and modelling of the excited
      state dynamics in the chromophores of GFP (HBDI) and the kindling fluorescent
      protein, KFP (FHBMI). The methods are ultrafast fluorescence spectroscopy with
      sub 50 fs time resolution and the modelling is based on the Smoluchowski
      equation. The excited state decays of both chromophores are very fast, longer for
      their anions than for the neutral form and independent of wavelength. Detailed
      studies show the mean fluorescence wavelength to be independent of time. The
      excited state decay times are also observed to be a very weak function of solvent
      polarity and viscosity. These results are modelled utilising recently calculated
      potential energy surfaces for the ground and excited states as a function of the
      twist coordinates about the two bridging bonds of the chromophore. For FHBMI and
      the scarce data on the neutral HBDI the calculations are not successful
      suggesting the need for refinement of these potential energy surfaces. For HBDI
      in methanol the simulation is successful provided a strong dependence of the
      radiationless decay rate on the coordinate is assumed. Such dependence should be
      included in future calculations of excited state dynamics. When the simulations
      are extended to more viscous solvents they fail to reproduce the observed weak
      viscosity dependence. The implications of these results for the nature of the
      coordinate leading to radiationless decay in the chromophore and for the
      photodynamics of fluorescent proteins are discussed.

PMID- 24020208
TI  - Ultrafast dual photoresponse of isolated biological chromophores: link to the
      photoinduced mode-specific non-adiabatic dynamics in proteins.
AB  - The anionic wild-type Green Fluorescent Protein (GFP) chromophore defines an
      entire class of naturally occurring chromophores, which are based on the oxydized
      tyrosine side chain. The GFP chromophore exhibits an enriched photoinduced non
      adiabatic dynamics in the multiple excited-state decay channels. Deactivation
      includes vibrational resonant photodetachment and internal conversion. Here, we
      provide detailed insight into the efficiency of different vibrational modes in
      promoting a selective photoresponse in the bare GFP chromophore anion. We
      introduce a general theoretical model that is capable of accounting for the
      alternative non-equivalent pathways in internal conversion, and we outline the
      factors, by which the photo-initiated response may be altered in this channel.
      The topography around the planar minimum in S1 and the two distinct types of the
      S1/S0 conical intersections obtained through high-level ab initio calculations
      provide direct support to the proposed model. There are mode-selective ways to
      control the photoresponse and to direct it towards a single excited-state decay
      channel. By tuning the excitation wavelength, the photoresponse may be directed
      towards the ultrafast non-statistical electron emission coupled with vibrational
      (de)coherence, whereas a vibrational pre-excitation in the ground state may lead
      to the ultrafast non-statistical internal conversion through a conical
      intersection. We also discuss the implication of our results to the photo
      initiated non-adiabatic dynamics in the proteins.

PMID- 24020209
TI  - Excited state dynamics of Photoactive Yellow Protein chromophores elucidated by
      high-resolution spectroscopy and ab initio calculations.
AB  - We report on experimental high-resolution spectroscopic studies in combination
      with advanced theoretical calculations that focus on the excited-state dynamics
      of various forms of the chromophore of the Photoactive Yellow Protein (PYP), and
      the dependence of these dynamics on conformational and isosteric structure, as
      well as the biological environment. Three-colour nanosecond multiphoton
      ionization pump-probe studies confirm and extend previous conclusions that the
      dominant decay channel of the lowest excited pipi* state (the so-called V' state)
      of methyl-4-hydroxycinnamate is picosecond internal conversion to the
      adiabatically lower nPi* state, and enable us to resolve apparent contradictions
      with picosecond pump-probe studies. Comparison of multiphoton ionization and
      laser induced fluorescence excitation spectra leads to the assignment of the
      hitherto elusive excitation spectrum of the V(pipi*) state. Complexation of
      methyl-4-hydroxycinnamate with water radically changes the excited-state
      dynamics; internal conversion to the npi* state is absent, and bond isomerization
      channels instead play a prominent role. Excited states of the thio-ester
      compound, the form in which the chromophore is present in PYP, have till the
      present study remained out of reach of gas-phase studies. The excitation spectra
      obtained here show a broad, almost structureless band system, giving evidence for
      enhanced nonradiative decay channels. The gas-phase results will be discussed in
      the context of results from ultrafast studies on these two chromophores in
      solution.

PMID- 24020210
TI  - Designs for molecular circuits that use electronic coherence.
AB  - The mounting evidence of recent years regarding long-lived coherent dynamics of
      electronic excitations in several light-harvesting antenna proteins suggests the
      possibility of realizing and exploiting light-initiated quantum dynamics in
      synthetic molecular devices based on electronic energy transfer. Inspired by the
      field of molecular logic, we focus this discussion on the prospect of using
      quantum coherence to control the direction of energy flow in a molecular circuit.
      As a prototype system we consider a circuit consisting of three chromophores that
      deliver energy to two trap chromophores. Our aim is to control to which trap the
      energy is more likely to be delivered. This is achieved by switching one of the
      circuit chromophores ON and OFF from the system, such that the direction of
      energy flow substantially changes from the ON and OFF states of the circuit. We
      find that quantum coherence can allow a significant ability to direct energy
      transfer in the circuit. However, when realistic levels of noise are added,
      quantum coherence only slightly improves the ability to direct electronic energy
      in comparison to a classical hopping mechanism.

PMID- 24020211
TI  - Time-resolved photoemission on the attosecond scale: opportunities and
      challenges.
AB  - The interaction of laser pulses of sub-femtosecond duration with matter opened up
      the opportunity to explore electronic processes on their natural time scale. One
      central conceptual question posed by the observation of photoemission in real
      time is whether the ejection of the photoelectron wavepacket occurs
      instantaneously, or whether the response time to photoabsorption is finite
      leading to a time delay in photoemission. Recent experimental progress exploring
      attosecond streaking and RABBIT techniques find relative time delays between the
      photoemission from different atomic substates to be of the order of -20
      attoseconds. We present ab initio simulations for both one- and two-electron
      systems which allow the determination of both absolute and relative time delays
      with -1 attosecond precision. We show that the intrinsic time shift of the
      photoionization process encoded in the Eisenbud-Wigner-Smith delay time can be
      unambiguously disentangled from measurement-induced time delays in a pump-probe
      setting when the photoionized electronic wavepacket is probed by a modestly
      strong infrared streaking field. We identify distinct contributions due to
      initial-state polarization, Coulomb-laser coupling in the final continuum state
      as well as final-state interaction with the entangled residual ionic state.
      Extensions to multi-electron systems and to the extraction of time information in
      the presence of decohering processes are discussed.

PMID- 24020212
TI  - How quasi-free holes and electrons are generated in organic photovoltaic
      interfaces.
AB  - We introduced a minimal model of the donor-acceptor interface encountered in
      organic solar cells to explain the efficient generation of free charges in these
      systems and we investigated the nature of charge transfer states formed by a
      delocalized exciton in the donor component. Contrarily to the generally accepted
      view excitons do not generate strongly bound hole-electron pairs, but relatively
      delocalized charge transfer states with energy very close to the energy of free
      holes and electrons. These states are kinetically more accessible from the
      exciton state and very close in structure to the free hole and electron states.
      The most relevant molecular parameter that affects the rate of exciton
      dissociation is the electronic coupling between donor orbitals and acceptor
      orbitals, i.e. the band widths of the donor and acceptor materials. Moreover, and
      to some surprise, we find that the process of charge separation is mostly a
      purely electronic process and a very similar physics can be described neglecting
      the role of nuclear degrees of freedom altogether.

PMID- 24020214
TI  - Active and passive control of zinc phthalocyanine photodynamics.
AB  - In this work we report on the ultrafast photodynamics of the photosensitizer zinc
      phthalocyanine (ZnPc) and manipulation thereof. Two approaches are followed:
      active control via pulse shaping and passive control via strategic manipulation
      in the periphery of the molecular structure. The objective of both of these
      control experiments is the same: to enhance the yield of the functional pathway
      and to minimize loss channels. The aim of the active control experiments is to
      increase the intersystem crossing yield in ZnPc, which is important for
      application in photodynamic therapy (PDT). Pulse shaping allowed an improvement
      in triplet to singlet ratio of 15% as compared to a transform-limited pulse. This
      effect is ascribed to a control mechanism that utilizes multiphoton pathways to
      higher-lying states from where intersystem crossing is more likely to occur. The
      passive control experiments are performed on ZnPc derivatives deposited onto
      TiO2, serving as a model system of a dye-sensitized solar cell (DSSC).
      Modification of the anchoring ligand of the molecular structure resulted in an
      increased rate for electron injection into TiO2 and slower back electron
      transfer, improving the DSSC efficiency.

PMID- 24020215
TI  - Strong field control of predissociation dynamics.
AB  - Strong field control scenarios are investigated in the CH3I predissociation
      dynamics at the origin of the second absorption B-band, in which state-selective
      electronic predissociation occurs through the crossing with a valence
      dissociative state. Dynamic Stark control (DSC) and pump-dump strategies are
      shown capable of altering both the predissociation lifetime and the product
      branching ratio.

PMID- 24020216
TI  - Formation of fragment ions (H+, H3+, CH3+) from ethane in intense femtosecond
      laser fields--from understanding to control.
AB  - The dissociative ionization of ethane in intense femtosecond laser fields has
      been investigated as a function of the laser pulse shape by systematically
      varying the quadratic spectral phase, i.e. the linear chirp. A very pronounced
      effect of the sign of the chirp is observed for the parent ion and all fragment
      ion yields, all ion yields being strongly favored by negative chirp of the laser
      field. The ratio of the H3+ ion yield to H+ ion yield can also be manipulated by
      changing the linear chirp, the maximum being observed for a significantly smaller
      chirp value than that for the individual ion yields. Since the H+ ions and the
      H3+ ions predominantly originate from the dication of ethane, this indicates
      control of fragmentation within one charge state of the ethane. Additional
      experiments performed with d3-ethane demonstrate that the control is operative
      prior to the statistical scrambling of hydrogen atoms, further supporting the
      concept of intra-charge-state control. In the case of formation of CH3+ ions two
      different ensembles occur, one from the monocation, another from the dication.
      The ratio of these ensembles can again be controlled by means of the linear chirp
      parameter implying control between the two different charge states (inter-charge
      state control).

PMID- 24020217
TI  - On the possibility of enhanced multiple ionization near conical intersections.
AB  - Recent measurements of the transient laser-induced fragmentation of photoexcited
      1,3-cyclohexadiene undergoing isomerization have seen that some of the fragments
      have higher velocity at the pump-probe delay corresponding to the time of passage
      through a conical intersection (Coln). (http://arxiv.org/abs/1212.3728) Here we
      explore several possible explanations related to the electronic and ionic
      structure of molecules in the vicinity of Colns and suggest some experimental
      tests that could illuminate the mechanism and ultimately control this behaviour.

PMID- 24020218
TI  - Coherent one-photon phase control in closed and open quantum systems: a general
      master equation approach.
AB  - The underlying mechanisms for one photon phase control are revealed through a
      master equation approach. Specifically, two mechanisms are identified, one
      operating on the laser time scale and the other on the time scale of the system
      bath interaction. The effects of the secular and non-secular Markovian
      approximations are carefully examined.

PMID- 24020219
TI  - Photophysics of fulvene under the non-resonant stark effect. Shaping the conical
      intersection seam.
AB  - We introduce a mechanistic strategy to control the excited state lifetime of
      fulvene based on shaping the topography of an extended seam of intersection with
      the non-resonant dynamic Stark effect. Fulvene has a very short excited state
      lifetime due to an energetically accessible seam of intersection which lies along
      the methylene torsion coordinate, and the initial decay occurs at the seam
      segment around the planar conical intersection structure. We have followed a
      three-step approach to simulate the control. First, we have calculated the effect
      of a non-resonant electric field on the potential energy surface at the ab initio
      level, including the field in a self-consistent way. The relative energy of the
      planar segment of the seam is increased by the non-resonant field. In the second
      step we simulate the control carrying out MCTDH quantum dynamics propagations
      under a static non-resonant field to derive the main control mechanisms. At
      moderately intense fields (epsilon < or = 0.03 a.u.) the decay is faster as
      compared to the field free case because the vibrational overlap between the
      excited and ground state vibrational functions is increased. However, at more
      intense fields (epsilon = 0.04 a.u.) the planar conical intersection is
      energetically inaccessible and the decay occurs at a slower time scale, at the
      segment of the seam with more twisted geometries. In the third step, the control
      over the dynamics is exerted with a non-resonant dynamic field. The acceleration
      of the decay due to the improved vibrational overlap does not occur, but the
      decay can be made slower with a dynamic field of 0.08 a.u. The results show the
      viability of our approach to control the photophysics shaping the topology of the
      conical intersection seam, and they prove that the extended nature of the seam is
      crucial for simulating and understanding the control.

PMID- 24020221
TI  - Photoinitiated quantum molecular dynamics: concluding remarks.

PMID- 24020220
TI  - General discussion.

PMID- 24020222
TI  - Biosimilars in the Caribbean--key considerations.

PMID- 24020223
TI  - Effect of Gongronema latifolium ethanol leaf extract on gastric acid secretion
      and cytoprotection in streptozotocin-induced diabetic rats.
AB  - OBJECTIVES: Gongronema latifolium leaves have been used in folklore medicine to
      manage diabetes mellitus and alleviate dyspepsia. This study aimed to provide a
      pharmacological basis to the medicinal use ofGongronema latifolium as an
      antidiabetic and antiulcerogenic agent in diabetes mellitus. METHODS: Ethanol
      extract from the leaf (200 mg/kg bodyweight) of Gongronema latifolium was
      administered to both streptozotocin-induced diabetic and control groups orally
      for 14 days. Gastric acid secretion was measured and ulcer was induced using
      ethanol and four-hour pyloric ligation. RESULTS: The mean bodyweight was
      significantly lower (p < 0.01), while the mean weight of the stomach, liver and
      small intestine to bodyweight ratio was increased significantly (p < 0.05) in the
      two diabetic groups compared to control. Extract significantly (p < 0.01) reduced
      the blood glucose level similar to the non-diabetic control. Basal and stimulated
      acid secretion in diabetic control rats was significantly (p < 0.01) decreased
      when compared to control. Extract administration increased the stimulated gastric
      acid secretion to a level significantly (p < 0.05) higher than control while
      reduction in gastric secretion by ranitidine was similar compared with control.
      Gongronema latifolium treatment significantly (p < 0.05) reduced ulcer scores in
      both ulcer models and increased mucus weight in the diabetic group. CONCLUSION:
      These results suggest that Gongronema latifolium antiulcerative activity is due
      to its prevention of chemical-induced stomach injury.

PMID- 24020224
TI  - The antimicrobial screening of a Barbadian medicinal plant with indications for
      use in the treatment of diabetic wound infections.
AB  - OBJECTIVE: Diabetes mellitus is a chronic non-communicable disease with high
      prevalence in the North American and Caribbean region. Diabetic Foot Syndrome
      which is an associated complication can lead to the development of wounds and
      ulcers which can become infected. Justicia secunda, a plant known locally in
      Barbados as Bloodroot used in folklore for wound healing, was selected to test
      its ability to aid diabetic wound healing by antimicrobial activity. It was
      therefore tested against the bacteria Staphylococcus aureus ATCC 25923,
      Pseudomonas aeruginosa ATCC 27853, and Enterococcus feacalis (clincal strain)
      which are commonly found in diabetic wounds. METHODS: The plant was collected by
      local users. Methanol and acetone extracts of the plant were prepared with use of
      soxhlet extraction. The antimicrobial activity was assessed with the use of a
      modified Kirby-Baurer method. Concentrations of 200 mg/ml, 100 mg/ml, 10 mg/ml,
      and 1 mg/ml of the extract were used, with a standard ciprofloxacin 5 microg
      positive control, and a 5% dimethyl sulfoxide (DMSO) solution negative control.
      RESULTS: The J secunda methanol and acetone extracts with an extraction yield of
      15.3% and 0.75%, respectively yielded no activity within the concentration range
      against the three strains of bacteria tested. In comparison with the positive
      control, relative inhibition zone diameter (RIZD) values of 0% resulted for both
      the negative control and the extracts, with the positive control having a value
      of 100%. CONCLUSION: The in vitro screen of the extracts prepared from J secunda,
      yielded no antimicrobial activity against the three strains of bacteria tested
      and therefore does not support the folklore claims by this mechanism of action.

PMID- 24020225
TI  - Total laparoscopic hysterectomy versus vaginal hysterectomy at the University
      Hospital of the West Indies: a 5-year retrospective study.
AB  - OBJECTIVE: To compare the outcomes of total laparoscopic hysterectomy (TLH), a
      relatively new procedure, with vaginal hysterectomy (VH), a well-established
      procedure, in a university teaching hospital. SUBJECTS AND METHODS: A
      retrospective chart review of all patients who underwent TLH at the University
      Hospital of the West Indies between January 2007 and December 2011 was conducted.
      Chart review was also conducted of a group of patients who underwent VH during
      this time period. The groups were compared with respect to demographic data and
      intraoperative and postoperative outcomes. Statistical analysis was undertaken
      using the SPSS software, version 12.0 (SPSS, Chicago, IL). The Student unpaired t
      test was used to analyse continuous variables, and the Chi-square test and Fisher
      exact test for categorical variables, when appropriate. A p-value of < 0.05 was
      considered statistically significant. RESULTS: Ten patients underwent TLH, and
      were compared with 22 women who underwent VH. There was no statistically
      significant difference between groups in uterine weight, estimated blood loss,
      postoperative analgesic requirement, or length of hospitalization. Total
      laparoscopic hysterectomy took significantly longer to perform (209.9 vs 145.6
      minutes, p = 0.004). One patient in the TLH group had to be brought back to the
      operating theatre after three months because of bowel prolapse secondary to vault
      dehiscence. With the exception of one case of bladder injury in the VH group,
      there were no significant differences between the groups in terms of
      intraoperative and postoperative complications. CONCLUSION: Total laparoscopic
      hysterectomy, notwithstanding its learning curve, is as safe as VH However, TLH
      was associated with a significantly longer operative time.

PMID- 24020226
TI  - Endothelial dysfunction in primary Sjogren syndrome.
AB  - OBJECTIVE: In this study, we aimed to investigate endothelial functions in
      primary Sjogren syndrome. METHODS: Thirty-five patients with primary Sjogren
      syndrome and 20 age and sex-matched healthy volunteers were recruited to the
      present study. Flow mediated dilatation of brachial artery and carotid intima
      media thickness were measured in the study population. RESULTS: Carotid intima
      media thickness values were similar between groups (0.50 +/- 0.10, 0.53 +/- 0.08,
      p > 0.05). Flow mediated dilatation of the brachial artery was disrupted in the
      primary Sjogren syndrome group (7% vs 12%, p = 0.002). CONCLUSION: There is
      endothelial dysfunction in patients with primary Sjogren syndrome, although they
      had comparable carotid intima-media thickness with the healthy control group.

PMID- 24020227
TI  - Prevalence of high-risk sexual behaviour in Jamaican adults and its relationship
      to sociodemographic and religious factors: findings from the Jamaica Health and
      Lifestyle Survey 2007-2008.
AB  - OBJECTIVE: To estimate the prevalence of high-risk sexual behaviours among
      Jamaican adults and evaluate associations with sociodemographic and religious
      factors. METHODS: We performed a cross-sectional study, using a nationally
      representative sample of Jamaicans, 15-74 years old. Participants completed an
      interviewer-administered questionnaire including questions on sexual activity,
      sociodemographic factors and religious practice. Having two or more sexual
      partners in the past year, non-use of condoms among persons with multiple
      partners and a history of previous sexually transmitted infection (STI) were the
      high-risk characteristics considered in the analysis. We obtained crude and
      category specific prevalence estimates for high-risk behaviour and estimated odds
      ratios for association with sociodemographic and religious factors. RESULTS: Data
      from 2833 participants who reported on sexually activity were analysed.
      Approximately 25% (95% CI 22, 27) of Jamaican adults had two or more sexual
      partners in the past year while 15% (95% CI 13, 17) had a past history of an STI.
      Approximately 6% (95% CI 5, 7) of persons with multiple partners did not use
      condoms during sexual intercourse. Overall, 32% (95% CI 30, 35) had any one of
      the three high-risk characteristics (male, 48%; female, 17%, p < 0.001). Being
      married, active religious practice and weekly attendance at religious meetings
      were associated with lower odds of high-risk sexual behaviour while being in a
      visiting relationship was associated with higher odds of high-risk behaviour
      CONCLUSION: A third of Jamaicans reported sexual practices that increase their
      risk of HIV infection. High-risk sexual behaviour was more common among men.
      Being married and weekly attendance at religious services were associated with
      lower odds of high-risk behaviour

PMID- 24020228
TI  - Nephropathy following type 2 diabetes mellitus in Tunisian population.
AB  - OBJECTIVE: The purpose was to compare the characteristics of Tunisians with Type
      2 diabetes mellitus (Type 2 DM) and nephropathy with those without nephropathy.
      This study assessed whether or not phenotypic characteristics can predict
      nephropathy development in Type 2 DM. The prevalence of nephropathy in Tunisian
      Type 2 DM patients, and their relationship with clinical and biochemical factors
      as well as chronic complications of the disease were determined. METHODS: This
      was a cross-sectional study of patients with diabetes diagnosed between January
      2008 and December 2010. Altogether, 73 Type 2 DM and 42 healthy volunteers from
      the Basic Health Group of Sousse, were targeted for the study. Clinical,
      biochemical data, as well as complications of diabetes were collected. Kidney
      malfunction was defined by glomerular filtration rate (GFR). RESULTS: Diabetic
      patients were older Diabetic women were more likely to have higher body mass
      index than men (p = 0.004). Obesity was more in women than men (60/23%).
      Complications including hypertension and dyslipidaemia were co-associated in
      women. Urinary creatinine clearance in Type 2 DM patients without nephropathy was
      significantly lower than in healthy participants (p < 0.0001). Microalbuminuria
      and urinary creatinine clearance were associated only in women with Type 2 DM
      with nephropathy (R2 = 0.95); 1.5% of Type 2 DM patients without nephropathy had
      GFR < 60 mL/min/1.73m2 and 76% had a GFR between 60 and 89 mL/min/1.73m2.
      Glomerular filtration rate difference between Type 2 DM patients with/without
      nephropathy, as well as between Type 2 DM patients with nephropathy/Type 2 DM
      without nephropathy, and with retinopathy was not significant. CONCLUSIONS: By
      analysing factors associated with nephropathy in Type 2 DM Tunisian patients,
      this study demonstrated their susceptibility to nephropathy. In addition,
      retinopathy is potentially associated with incipient nephropathy in Type 2 DM
      Tunisian patients.

PMID- 24020229
TI  - Alcohol use and associated factors among adolescent students in Thailand.
AB  - OBJECTIVE: Alcohol misuse is a relevant public health issue in Thailand. The
      assessment of the prevalence of alcohol use among adolescents may guide policies
      and programmes aimed at reducing alcohol use among this age group. METHOD: Using
      data from the Thailand Global School-based Student Health Survey (GSHS) 2008, we
      assessed the prevalence of alcohol use and the associated factors among
      adolescents (n = 2758). RESULTS: Overall, the prevalence of current alcohol use
      was 14.8% (21.2% males and 9.3% females). Variables positively associated with
      the outcome in multivariable analysis among boys were older age, other substance
      use (smoking and illicit drug use), sex in the past 12 months, physical fighting,
      injury in the past 12 months; and among girls, poverty, smoking, physical
      fighting and lack of parental or guardian connectedness. CONCLUSION: Efforts to
      prevent and control alcohol misuse may need to address a cluster of risk
      behaviours including cigarette smoking.

PMID- 24020230
TI  - Validation of the Jamaican Maternal Sexual Role Modelling Questionnaire.
AB  - OBJECTIVE: Urban Jamaican adolescent girls face significant risk for sexually
      transmitted infections including HIV Studies from the United States ofAmerica
      have found that parents influence adolescents' sexual risk attitudes and
      behaviours through parent-child sexual communication and monitoring/supervision.
      Data from an ongoing mother-daughter HIVrisk reduction intervention study in
      Kingston, Jamaica identified an additional influence of adolescent girls' sexual
      risk - maternal sexual role modelling (MSRM). As no reliable and valid
      questionnaires existed to measure MSRM, one was developed. The objective of the
      current study was to evaluate the psychometric properties of the Jamaican
      Maternal Sexual Role Modelling questionnaire. METHOD: Data were collected from
      209 Jamaican female adolescents recruited from Kingston, St Andrew and St
      Catherine parishes. RESULTS: The final 19-item Jamaican MSRM questionnaire was
      found to have excellent internal reliability (Cronbach's alpha = 0.89). Content
      validity expert ratings and modified kappa statistics were all 1.0. Principal
      component analysis identified a three-factor structure that accounted for 53.7%
      of the variance. Greater MSRM scale scores, indicating more positive and
      protective maternal sexual role modelling, were associated with less sexual
      experience, lower intentions to have sex, greater intentions to use condoms if
      having sex and greater condom use self-efficacy among adolescent girls.
      CONCLUSION: The MSRM scale was found to be a reliable and valid measure of
      Jamaican adolescent females'perceptions of their mothers'sexual role modelling.
      Further research is needed to assess the reliability and validity of the
      instrument with other populations.

PMID- 24020231
TI  - Ultrasound detected asymptomatic cholelithiasis: an age-based protocol for
      management.
AB  - OBJECTIVE: This study was undertaken to examine the correlation between age and
      gender and the presence of ultrasound findings of acute or chronic cholecystitis
      in adultpatients with cholelithiasis. METHOD: The demographic data of all
      patients diagnosed with cholelithiasis and cholecystitis on ultrasound between
      January 1, 2002 and December 31, 2006 were reviewed and statistically analysed.
      RESULTS: Five hundred adults, 373 females (74.6%) and 127 males (25.4%), were
      diagnosed with cholelithiasis during the five-year period. Ages ranged from 18 to
      94 years with a median age of 47 years. The diagnosis of cholecystitis was
      equivocal in 11 patients. Of the remaining 489, 22.1% (108) were diagnosed as
      positive for cholecystitis by ultrasound, the remaining 77.9% (381) being
      negative. No association was found between gender and cholecysytitis in bivariate
      analysis, (chi2 = 1.82, df =1, p = 0.177). A statistically significant relation
      was found between age group category and ultrasound-determined cholecystitis
      status (chi2 = 32.58, df= 4, p < 0.001). Higher proportions of persons in the 20
      39-year (40.9%) and 40-59-year (20.4%) age groups had cholecystitis on ultrasound
      examination compared to other age categories where corresponding rates were
      approximately 11% or less. CONCLUSION: Patients 60 years or older who were
      diagnosed with cholelithiasis on ultrasound examination were less likely to have
      cholecystitis than younger patients.

PMID- 24020232
TI  - Evaluation and management of hypertension in the elderly.
AB  - Treatment of hypertension in the elderly is a challenge. Elevated blood pressure
      (> 140/80 mmHg) in the elderly (60+ years) can be either systolic, diastolic or
      combination of both. Arterial stiffness, intimal hyperplasia and non-compliance
      of the vascular tree have been underlying factors. Prevalence of hypertension
      increases with advancing age and varies with the population under study;
      therefore screening this population should not only be limited to those at risk.
      Presentation is often due to complications such as stroke, cardiovascular events,
      and erectile dysfunction or due to presentation of an unrelated disorder The
      presence of co-morbidity, drug interaction and their side effects should be
      considered in the management of hypertension in the elderly. With the advent of
      several classes of antihypertensives, there is no shortage of drug options for
      treatment of hypertension in the elderly, but a careful and individualized
      approach is needed.

PMID- 24020233
TI  - Keratinophilic fungi recovered from feathers of different species of birds in St
      Kitts and Nevis.
AB  - OBJECTIVE: The aim of the present study was to investigate the occurrence of
      keratinophilic fungi including dermatophytes on feathers of domestic and wild
      birds in the islands of St Kitts and Nevis. METHODS: During 2010-2011, samples of
      feathers from ninety-four birds were examined by hair-baiting technique in Petri
      dishes containing sterilized soil. Fungal growths appearing on the feathers and
      the hair-baits were microscopically examined and the cultures obtained were
      identified on the basis of their microscopic and colonial morphology. RESULTS:
      Chrysosporium constituted the majority (86.9%) of the 72 isolates of
      keratinophilic fungi, represented by mainly C tropicum and C indicum. Sepedonium
      spp isolates were recovered from nine of the feather samples; two of these were
      identified as Sepedonium chrysospermum, and the other two as S ampullosporum.
      CONCLUSION: Recovery of four isolates of the dermatophyte, Microsporum gypseum
      complex (two each of M gyspeum and M fulvum) from feathers of birds is a finding
      of public health significance.

PMID- 24020234
TI  - Emerging applications of an experimental single photon emission computed
      tomography: an analysis of 16 areas of interest in the pig's model.
AB  - This paper aims to affirm various new applications of single photon emission
      computed tomography (SPECT) technique by utilizing the pig's models. Evaluation
      and subsequent analysis of SPECT results was conducted on the jaws of eight
      experimental pigs with a total of 16 areas of interest. The various reasons for
      which each experiment was conducted were evaluated and these reasons include: i)
      validation of a new bone grafting technique for closure of oro-antral
      communications, ii) comparison of autogeneous bone graft with other bone grafts,
      iii) sequential confirmation of osteoblastic activity of the sandwich bone
      regeneration technique with another technique, iv) validation of the use of a new
      membrane for guided tissue regeneration (GTR), v) validation of the fact that
      osseointegration is better with beaded implants than with threaded implants, and
      vi) validation of the fact that GTR is essential for immediate implant practice.
      The outcome of this evaluation is critically analysed against the background of
      the substantial clinical evidence where applicable, so as to appreciate the
      position of SPECT Following the evaluation of 16 areas of interest in eight
      experimental pigs, it was shown that experimental SPECT was valuable in the
      validation of the above reasons. It appears to be a modality that can
      continuously be utilized to validate and compare situations which would display
      osteoblastic activities. It is concluded that the bone scintigraphy imaging
      technique accurately reflects osteoblastic activities and can now be used to
      validate osseointegration of any implant or bone-grafting system. This can be
      done in conjunction with histological and histomorphometic analysis and such
      results obtained from SPECT should be correlated with the histological and
      histomorphometric analysis if available.

PMID- 24020235
TI  - Getting to zero: male circumcision for HIV prevention in The Bahamas.

PMID- 24020236
TI  - Another small supernumerary marker chromosome derived from chromosome 9 in a
      Klinefelter patient.
AB  - Marker chromosomes are very rare in Klinefelter patients and phenotypic findings
      are related to the affected chromosomal region. The phenotypic effects of small
      supernumerary marker chromosomes (sSMC) range from multiple malformations/mental
      retardation to no effect (ie a normal phenotype). This wide spectrum of
      phenotypes is due to the origin, structure and gene content of the marker
      chromosome. The first Klinefelter case with sSMC 9 was published by Liehr et al
      in 2005. The present case was referred for chromosomal analysis because of
      dysmorphic features, speech delay and mild mental retardation. Conventional
      cytogenetic analysis revealed the 47XXY karyotype in 17 metaphases and the 48 XXY
      + marker karyotype in eight metaphases. Fluorescence in situ hybridization (FISH)
      analysis to identify the marker chromosome was performed using the LSI p16 (9p21)
      Spectrum Orange/CEP 9 SpectrumGreen Probe (Vysis CDKN2A/CEP 9 FISH Probe) and
      partial trisomy 9 mosaicism was confirmed in this patient. To our knowledge, this
      is the second case of Klinefelter syndrome with a small supernumerary marker
      chromosome derived from chromosome 9.

PMID- 24020237
TI  - Coexistence of glucocorticoid resistance and pseudohypoparathyroidism.
AB  - We report for the first time the case of a young man who developed both
      glucocorticoid resistance and resistance to parathyroid hormone. Treatment with
      high doses of dexamethasone together with administration of calcium and
      calcitriol resulted in a significant improvement in the patients condition. In
      this paper, we discuss in detail diagnostic and treatment strategies used on the
      patient and the impact on the course and outcome of both disorders. We associate
      the development of both these disorders with a possible inherited defect in the
      signal pathways common to glucocorticoid and parathyroid hormone receptors.

PMID- 24020239
TI  - Marfan's syndrome: pre-pubertal aortic rupture with left coronary artery
      aneurysms and fistulas.
AB  - Aortic dissection and rupture occur in 20-40% of patients with Marfan's syndrome.
      This occurs predominantly in the third and fourth decade of life, contributing to
      the increased morbidity and mortality of this specific group of patients. This is
      the first known documented case report of prepubertal left coronary sinus rupture
      with left coronary artery aneurysms with fistulous communication to both the
      superior vena cava and right superior pulmonary vein, presenting with a
      continuous murmur

PMID- 24020240
TI  - [Single file endodontic treatment: a new era?].
AB  - Root canal shaping is one of the key stages of endodontic treatment, when
      performed properly, it is a predictive factor for the outcome of the treatment.
      It is critical for an adequate disinfection, which is more effective at the
      completion of a proper shaping procedure. The introduction of NiTi instruments
      into endodontic greatly improved the root canal shaping and decreased the time
      required for a full mechanical preparation. Over the last 2 decades, numerous
      attempts have been made to further improve the procedure with a wide range of
      rotary NiTi endodontic file systems. All these systems require several subsequent
      files. Recently, three different concepts of single-file systems have been
      introduced: 1. The single file reciprocating working motion: it consists of a
      reciprocating counterclockwise and a clockwise motion. This reciprocal motion
      reduces torsional loads thus, allows safer instrumentation with less working
      time. 2. Single-file instrumentation using full 360 degrees rotational movement
      to be used in a full clockwise rotation. Some of these files also have an Anti
      Breakage Control (ABC) which protects from catastrophic procedural malfunction by
      unwinding of these file before breakage. 3. The Self-Adjusting File (SAF) which
      is a thin-walled, pointed cylinder, hollow nickel-titanium endodontic file that
      is elastically compressible into a root canal that has been previously negotiated
      using a #20 hand file and can widened inside it, facilitating removal of debris
      and dentin from the canal wall. The file conforms to the canal shape and permits
      irrigant flow through the file. The SAF works in a combined vibrating and partial
      rotational motions, and circumferentially simultaneously enlarging and irrigating
      the canal. The objectives of these new approaches is to reduce the working time
      and cost and improve safety of the shaping procedure, and suggest to have a lower
      procedural errors incidents. Few studies, conducted in the recent years, using
      these new instruments demonstrated an excellent shaping and centering ability of
      these new systems. They produce smooth tapered canal preparations with
      reproducible results, even when performed by less experienced practitioners. As
      mentioned above, these new techniques appeared to be promising, but further
      fundamental clinical and laboratory studies are needed to confirm their
      abilities.

PMID- 24020238
TI  - A reduced grade of liver fibro-steatosis after raltegravir, maraviroc and
      fosamprenavir in an HIV/HCV co-infected patient with chronic hepatitis,
      cardiomyopathy, intolerance to nelfinavir and a marked increase of serum creatine
      phosphokinase levels probably related to integrase inhibitor use.
AB  - The use of new antiretroviral drugs in HIV infection is particularly important in
      patients with intolerance or resistance to other antiretroviral agents.
      Raltegravir and maraviroc represent new, important resources in salvage regimens.
      A reduced grade of liver fibro-steatosis after a combination of raltegravir and
      maraviroc (second-line) has not been studied and the mechanism by which these new
      drug classes induced a marked reduction of grade of liver diseases is currently
      unknown. In the present case report, nested in an ongoing multicentre
      observational study on the use of new antiretroviral inhibitors in heavy
      treatment-experienced HIV patients, we evaluated the correlation between a "short
      therapeutic regimen" raltegravir maraviroc and fosamprenavir and liver diseases.
      The aim of this report is to describe the use of a three-drug regimen based on
      two novel-class antiretroviral agents (raltegravir and maraviroc) plus the
      protease inhibitor fosamprenavir, in an experienced HIV-infected patient with
      chronic progressive hepatitis C complicated by liver fibrosis; an overwhelming
      increased serum creatine kinase level occurred during treatment, and is probably
      related to integrase inhibitor administration. At present no information is
      available regarding this correlation.

PMID- 24020241
TI  - [Sandwich osteotomy--a biologic method for vertical augmentation of edentulous
      alveolar ridges].
AB  - Vertical augmentation for rehabilitation with dental implants poses a clinical
      challenge. The surgical obstacles have been extensively documented within the
      literature. Outcomes of the multiple methods available are not predictable, and
      overall success rates are sub-optimal. This paper presents the Sandwich Osteotomy
      Technique (interpositional rhBMP-2 and bone subtitute grafting) in a young female
      with congenital oligodontia. The uniqueness of this method, like in distraction
      osteogenesis, is that the segmental bone remains attached to the mucoperiosteal
      flap and thus the blood supply is maintained. Bone graft or substitute is
      introduced into the interpositional space that was created. Advantages of
      Sandwich Osteotomy are minimal bone exposure, good blood supply, no need for
      donor bone graft and minimal overall morbidity. Limitations of the technique are
      soft tissue stretching, gingival fibrosis, and high technical demand. According
      to our experience with this surgical method, vertical augmentation is stable up
      to 8 mm. Beyond this height approximately 10% bone resorption was noticed.

PMID- 24020242
TI  - [Screening saliva].
AB  - Oral Fluids (OF) are a complex mixture including components deriving from,
      salivary glands, blood, nasal and bronchial secretions, mucosal lining cells and
      microbiota. Therefore, OF as a mirror of the body, were suggested as an important
      diagnostic fluid for the detection of both, oral and systemic diseases. OF as
      diagnostic fluids have several advantages; their collection is easy, inexpensive
      and noninvasive, they are suitable for home use and for epidemiology researches,
      they are easy to store and ship, do not clot and enable fast detection. OF based
      diagnostics research accomplished a great advance during the last decade. This is
      mainly due to biotechnology improvements such as 2-D Fluorescence Difference Gel
      Electrophoresis, quantitative Mass Spectrometry and bioinformatics systems. These
      technologies enabled the detection of more than 3000 proteins in oral fluids, as
      well as the establishment of a panel of biomarkers to different human
      pathological conditions (i.e. periodontitis, Sjogren's Syndrome, oral cancer,
      pancreatic cancer etc). However, this diagnostic field has several drawbacks,
      mainly due to oral fluids variance composition, blood contamination as a result
      of gingivitis or mucosal injuries, the lack of a single established collection
      protocol and the presence of high abundant components in OF. This article
      summarizes the current research, and provides an outlook toward the foundation of
      this unique body fluid as a major player in the diagnostic field.

PMID- 24020243
TI  - [Retention or adhesion?].
AB  - One of the reasons for immediate or late failure of restorations is the
      detachment of the restoration from the tooth. Retention for the restoration could
      be achieved from axial walls (macromechanical retention) or from adhesion of the
      restoration to the remaining tooth structure. Adhesion relies on bonding of resin
      cement to enamel or dentin on one side and to the restorative material on the
      other side. Bonding to enamel is predictable. Good bonding to dentin is more of a
      challenge especially with indirect restorations. In those cases the restoration
      is delivered usually a few days after the tooth was prepared during this time the
      exposed dentin might be contaminated or damaged. The question is whether you can
      rely on adhesion when cementing indirect restorations? In order to achieve the
      maximal bonding strength to dentin, the hybrid layer on the dentin must be built
      immediately after tooth preparation. This procedure is called Immediate Dentin
      Sealing. In vitro and clinical studies have shown better performance of
      restorations cemented following the IDS procedure. The article discusses the
      rational and the protocol of this procedure. A clinical case is presented as an
      example for the possibilities following this philosophy.

PMID- 24020244
TI  - [Update and review of oral lichen planus].
AB  - Lichen planus is a chronic mucucutaneous disease affecting the oral cavity in up
      to 2% of the population. It has variable oral manifestations, may be asymptomatic
      or accompanied by severe pain. It has features which are similar to autoimmune
      diseases although its pathogenesis is not fully understood. Stress is associated
      with exacerbations and dental materials and/or medications can cause lichenoid
      reactions. Some reports link hepatitis C with the condition. The chronic nature
      of the disease, its occasional severity, the fact it is considered a pre
      malignant condition, together with its prevalence, make it essential for the
      general dentist to be aware and informed about it. The dentist's role is
      important at all stages includes a thorough clinical examination, identification
      pathological lesions, and following diagnosis, regular dental treatment and
      minimization of exacerbations. A specialist should be consulted regarding
      diagnosis and ongoing dental treatments. The specialist will add local or
      systemic treatments as needed and provide long-term follow-up in order to
      diagnose malignant changes as quickly as possible.

PMID- 24020245
TI  - [Community dentistry in practice: four decades of activity among the Ethiopian
      community].
AB  - The immigration absorption of the Ethiopian community poses a great Zionist
      challenge to the State of Israel. The Department of Community Dentistry
      established a long and ongoing relationship with this unique population on a
      variety of levels. We revealed an alarming deterioration of their oral health
      status since their arrival to Israel. Concurrently, we explored the association
      between oral health and psychosocial variables among these immigrants.
      Accordingly, we implemented a holistic community oral health care program
      (prevention, treatment, dental, medical, social, psychological), with the
      participation of a multidisciplinary team of Ethiopian born professionals. In
      addition, as part of the integration process in the Israeli society and
      workplace, our department educated and trained individuals of this community as
      dental assistants and dental hygienists in courses held at the Hadassah Medical
      Organization. We strongly believe that this model of relationship and support
      should be implemented on a national level.

PMID- 24020246
TI  - [Failure in the orthodontic treatment of impacted maxillary canines].
AB  - Maxillary canine impaction occurs in 1-3% of most Western populations and its
      orthodontic treatment is often difficult. Failure to resolve the impaction is not
      uncommon and may lead to malpractice lawsuits. The information in the literature
      about the reasons for non-resolution of this condition is sparse and
      unsubstantiated. This encourages the dispensing of inappropriate treatment that
      may result in severe tooth, soft and hard tissue damage as well as a prolonged
      treatment period. This review describes the epidemiology, pathogenesis and the
      wide range of reasons that may lead to failure to resolve the canine impaction.
      It shows that a lack of appreciation of anchorage demands and inaccurate
      positional diagnosis of the 3-D location and orientation of impacted teeth are
      the major reasons for failure. In addition, the review shows that invasive
      cervical root resorption (ICRR) is a frequently undiagnosed or unrecognized cause
      of failure of orthodontic resolution of impacted canines, and should be
      distinguished from replacement resorption (ankylosis). Corrective measures which
      may lead to successful treatment are further recommended. Special emphasis is
      placed on the crucial role of cone beam computerized tomography in the accurate
      radiographic diagnosis and early detection of pathology of impacted tooth and
      damage to adjacent anchor teeth. The importance of teamwork in achieving the best
      treatment outcome is stressed.

PMID- 24020247
TI  - [Esthetic restorations of primary anterior teeth].
AB  - Esthetic treatment of primary teeth is one of the greatest challenges to
      pediatric dentists. A variety of restorative options using full coverage are
      available for anterior primary teeth. In the last half century the emphasis on
      treatment of severely decayed primary teeth shifted from extraction to
      restoration. In the past, restorations consisted of placement of stainless steel
      crowns on severely decayed teeth. However, they are esthetically unacceptable
      today. Over the last decade parents expect a higher esthetic standard for their
      children's primary teeth. Thus, the restoration should provide esthetic
      appearance and durability in addition to restoring function. The purpose of this
      review is to describe the types of full coverage options for anterior primary
      teeth currently available.

PMID- 24020249
TI  - [60 years of excellence in dental education and research].

PMID- 24020248
TI  - [Ridge preservation after tooth extraction: what do we know today].
AB  - Following tooth removal, varying amounts of bone resorption take place due to
      qualitative and quantitative changes that occur at the alveolar bone around the
      extraction site. Alveolar bone is a tooth dependent structure and therefore,
      after a tooth is extracted, dimensional bone reduction takes place both,
      horizontally and vertically resulting in changes that may lead to esthetic and
      functional problems. Such deformities of the alveolar ridge may compromise future
      implant placement as well as esthetic results when a fixed partial denture is
      constructed in a visible area. In order to preserve ridge dimensions following
      tooth extraction, particularly where future implant placement is planned,
      ridge/socket preservation is recommended. Ridge/socket preservation is any
      procedure undertaken at the time of or following an extraction that is designed
      to minimize external resorption of the ridge and maximize bone formation within
      the socket. In certain situations it not advisable to perform ridge preservation
      at the time of tooth extraction thus, preservation is delayed by few weeks (6-8).
      This paper reviews the various socket/ridge preservation techniques and the
      diverse materials used to fill those deficient tissues or prevent their collapse.
      Scientific literature review is discussed.

PMID- 24020250
TI  - [Nutritional status of women with gestational diabetes and characteristics of
      newborn].
AB  - The objective was to determine the relationship between the mother's nutritional
      status and the newborn's gestational characteristics. A sample of 149 women with
      gestational diabetes was controlled in the High Risk Obstetric Unit of the
      Medical Specialties Public Health Center before delivery in the maternity ward of
      the Hospital Clinico Herminda Martin de Chillan, Chile in 2010. Data were
      obtained from the perinatal clinical history and the newborn's chart. The
      variables recorded for the mother were nutritional status, type of delivery,
      number of pregnancies, and metabolic control. Data for the newborn were weight,
      length, head circumference, and gestational diagnosis. These data were analyzed
      by ANOVA, Chi-square test, and Multiple Correspondence. Women with a normal
      nutritional status were multiparous with natural childbirth; the newborn had an
      adequate gestational age and normal head circumference. On the other hand,
      maternal obesity was related to a Cesarean; the newborn was large for gestational
      age and had a larger head circumference. Overweight women were primiparous and
      the newborn was small for gestational age with a smaller head circumference (p <
      0.01). It was concluded that obesity in women with gestational diabetes explains
      variables such as type of delivery, number of gestations, and the newborn's
      diagnosis.

PMID- 24020251
TI  - Daily consumption of foods and nutrients from institutional and home sources
      among young children attending two contrasting day-care centers in Guatemala
      City.
AB  - Adequate nutrition is critical to child development and institutions such as day
      care centers could potentially complement children's diets to achieve optimal
      daily intakes. The aim of the study was to describe the full-day diet of
      children, examining and contrasting the relative contribution of home-derived
      versus institutional energy and nutrient sources. The present comparison should
      be considered in the domain of a case-study format. The diets of 33, 3-6 y old
      children attending low-income day-care centers serving either 3 or a single meal
      were examined. The home-diet was assessed by means of 3 non-consecutive 24-hr
      recalls. Estimated energy and nutrient intakes at the centers and at home were
      assessed and related to Recommended Nutrient Intakes (RNI). Nutrient densities,
      critical densities and main sources of nutrients were computed. We observed that
      in children attending the day-care center serving three meals, home-foods
      contributed less than half the daily energy (47.7%) and between 29.9% and 53.5%
      of daily nutrients. In children receiving only lunch outside the home, energy
      contribution from the home was 83.9% and 304 kcal lower than for children
      receiving 3 meals. Furthermore, between 59.0% and 94.8% of daily nutrients were
      provided at home. Daily energy, nutrient intakes and nutrient densities were well
      above the nutrient requirements for this age group, and particularly high for
      vitamin A. The overall dietary variety was superior in the situation of greater
      contribution of home fare, but overall the nutrient density and adequacy of the
      aggregate intakes did not differ in any important manner.

PMID- 24020252
TI  - [Single central obesity and combined with overweight/obesity in preeschool
      Mexican children].
AB  - Waist circumference (WC) is a useful measure for identifying children at higher
      risk of complications related with abdominal fat. We determined the magnitude of
      central adiposity, single and combined with overweight and obesity in infants 1-5
      years old. We also identified smoothed age-and sex-specific WC percentile values,
      which were compared with other countries available data. This was a cross
      sectional study in children of 8 day care centers located in Monterrey, Mexico (n
      = 903, 431 boys and 472 girls). Because the risk due to abdominal obesity begins
      at WC percentile > or = 75, we considered two thresholds, percentile 75 y 90.
      Overweight was defined based on body mass index at percentile 85-94 for age and
      sex; and obesity, at percentile > or = 95. Analysis consisted of point prevalence
      and 95% confidence intervals. The LMS Chart Maker Light software was used for
      smoothing WC percentile values. The study population mean age was 2.7 +/- 1.0
      years. Mexican children's WC was 1 cm above that of Afro-American; and it was up
      to 4 cm below that Mexican-American. Prevalence of central obesity with WC at
      percentile 75 combined with overweight/obesity was 25.1% (95% CI 22.3-28.0) and
      single, 15.4% (95 CI% 13.0-17.8). Prevalence of single abdominal obesity with WC
      at percentile > or = 90 was 4.4% (IC 95% 3.0, 5.8). Day care centers represent a
      key opportunity for defying central obesity. WC can be used since early age for
      screening and caring children at higher cardiovascular risk.

PMID- 24020254
TI  - [Particular behavior of different Lactobacillus acidophilus strains in petit
      suisse cheese].
AB  - The objective of this study was to evaluate the physico-chemical and
      microbiological characteristics of petit-suisse cheeses manufactured with the
      addition of two Lactobacillus acidophilus strains: LA-14 (potentially probiotic)
      and La-5 (probiotic culture), using Streptococcus thermophilus TA040 as starter
      culture. Three cheese-making trials were prepared: Q1 (control: with TA040), Q2
      (with TA040 + LA-14), and Q3 (with TA040 + La-5). Parameters analyzed included
      microbial counts of probiotic, potentially probiotic and starter microorganisms,
      and physico-chemical parameters (pH and moisture) after 1, 7, 14, 21, and 28 days
      of storage of the product at 4 +/- 1 degree C. Viable counts of L. acidophilus
      remained between 7.46 and 7.62 log CFU g(-1) for La-5, and between 6.39 and 6.83
      log CFU g(-1) for LA-14. As for the starter, higher populations were observed for
      Q2 (9.58-9.68 log CFU g(-1)) and Q3 (9.42-9.79 log CFU g(-1)), when compared to
      Q1, which suggests synergism between L. acidophilus and the starter culture.
      Moisture and pH values remained stable for cheeses Q1, Q2, and Q3, and no
      significant differences were detected between cheeses after the first day of
      storage (p > 0.05). Particular features of both L. acidophilus strains determined
      different behavior in petit-suisse cheese, and the better adaptation of the La-5
      to the product environment was perceptible, since higher populations were
      observed when compared to LA-14.

PMID- 24020253
TI  - [Nutritional contribution of snacks to food patterns in school children who are
      overweight or obese compared to school children who are of normal weight in
      Cartago, Costa Rica].
AB  - In order to assess the nutritional contribution of snacks to food patterns in
      school children, a sample of 80 Costa Rican elementary schoolchildren: 40
      children who were overweight or obese (the case group) and 40 children with
      normal weight (the control group) were evaluated. The anthropometric evaluation
      included weight, height, and triceps skinfold thickness. Food patterns were
      determined using a 3-day food diary. Snacks consumed throughout the day were
      classified and analyzed according to their place of preparation and location of
      consumption and to the time of the day in which they were consumed. The results
      of this study revealed that "afternoon snacks" and "snacks prepared and eaten at
      home" were the most frequently consumed snacks by both case and control groups.
      The girls in the case group had a significantly larger intake of energy and
      carbohydrates in their "afternoon snacks" and the "snacks prepared and eaten at
      home" as compared to girls in the control group. Boys in the case group showed a
      significantly greater consumption of saturated fat in the "snacks prepared and
      eaten at home" as compared to boys in the control group. It was concluded that
      the intake of "afternoon snacks" and of those "prepared and eaten at home" could
      be related with the incidence of overweight/obesity in the sample of study and
      therefore nutrition education aimed at parents and children is crucial and could
      play an important role in its prevention.

PMID- 24020255
TI  - [Design of an HACCP program for a cocoa processing facility].
AB  - The HACCP plan is a food safety management tool used to control physical,
      chemical and biological hazards associated to food processing through all the
      processing chain. The aim of this work is to design a HACCP Plan for a Venezuelan
      cocoa processing facility.The production of safe food products requires that the
      HACCP system be built upon a solid foundation of prerequisite programs such as
      Good Manufacturing Practices (GMP) and Sanitation Standard Operating Procedures
      (SSOP). The existence and effectiveness of these prerequisite programs were
      previously assessed.Good Agriculture Practices (GAP) audit to cocoa nibs
      suppliers were performed. To develop the HACCP plan, the five preliminary tasks
      and the seven HACCP principles were accomplished according to Codex Alimentarius
      procedures. Three Critical Control Points (CCP) were identified using a decision
      tree: winnowing (control of ochratoxin A), roasting (Salmonella control) and
      metallic particles detection. For each CCP, Critical limits were established, the
      Monitoring procedures, Corrective actions, Procedures for Verification and
      Documentation concerning all procedures and records appropriate to these
      principles and their application was established. To implement and maintain a
      HACCP plan for this processing plant is suggested. Recently OchratoxinA (OTA) has
      been related to cocoa beans. Although the shell separation from the nib has been
      reported as an effective measure to control this chemical hazard, ochratoxin
      prevalence study in cocoa beans produced in the country is recommended, and
      validate the winnowing step as well

PMID- 24020256
TI  - [Effect of processing on the antioxidant capacity of the plum (Prunus
      domestica)].
AB  - Fruits are considered sources of antioxidant compounds whose properties could
      impair due to processing. The objective of this work was to determine the effect
      of blanching and osmotic dehydration on the total polyphenols content, tannins
      and antioxidant capacity of plums (Prunus domestica) in yellow and red varieties.
      The total phenolic content in plums was determined according to the Folin
      Ciocalteu assay and tannins were determined by vanillin assay. The antiradical
      efficiency (AE) and ferric reducing power (FRP) were used to estimate the total
      antioxidant capacity. The content of total polyphenols and tannins were higher in
      the red plum. The content of polyphenols in the pulp was higher that the peel
      while for tannins the opposite was observed in both varieties. The red plum had
      higher antioxidant capacity. The AE was low and slow kinetics for the two
      varieties. There was a linear correlation between polyphenols and tannins with
      antiradical efficiency; however, there was no correlation with the reducing
      power. The total polyphenols content was increased with blanching, while the
      tannins and the AE decreased, ferric reducing power is unaffected. For osmotic
      dehydration, the tannins and the AE were decreased, while the total polyphenols
      content and ferric reducing power are unaffected. It is recommended the blanched
      as an alternative to consumption and conservation in the plum.

PMID- 24020257
TI  - [Phytic phosphorus and phytase activity in cereal-based infant formulas].
AB  - Phytic acid is an organic acid present in cereal grains. The phosphorus inside
      its molecule (PPhy) is not available because of its low solubility, though the
      bioavailability could be increased by the activity of phytase enzymes (PhyA).
      With the purpose of quantifying the PPhy and PhyA in supplements manufactured
      from cereals and intended for lactating infants, five formulas of wide
      distribution in local markets were selected and identified depending on the main
      vegetable ingredients as A (rice), T (wheat), ATS (rice, wheat and soy isolate),
      ATM (rice, wheat and maize) and ATMS (rice, wheat, maize and soy isolate). Five
      samples were taken from each formula, each one corresponded to a commercial brand
      (400 to 500 g), coming from different batches and before their expiration date.
      The crude protein ranged from 7.2 to 16.8%, with de highest value for ATS and the
      lowest for T and ATM (P < 0.01). Ether extract varied from 0.31 to 0.75%, while
      the calcium: phosphorus ratio from 1.6 for ATM, to 1.1 for the rest. The PPhy was
      61.5% of the total phosphorus in T, with differences (P < 0.01) compared to the
      other formulas (39.9 +/- 6.8%). PhyA was only detected in ATS, T and ATM (152,
      300 and 570 U/kg, respectively). The chemical composition complied with the
      manufacturer report, with a high content of PPhy and PhyA associated to the wheat
      presence in the formula.

PMID- 24020258
TI  - Antioxidant activity of four color fractions of bee pollen from Merida,
      Venezuela.
AB  - Bee pollen has been reported to show antioxidant and radical scavenging
      activities; contributing to anti-inflammatory and gastroprotective properties.
      Venezuelan honeybee pollen has been little studied, but is consumed because its
      properties are known from other countries reports. On the basis of these reports,
      water, ethanol and methanol soluble fractions were prepared from dried bee-pollen
      commercially available and produced by La Montana farm (Merida, Venezuela). These
      fractions were evaluated for their functional properties, specifically,
      polyphenol content and total antioxidant activity. Pollen samples were separated
      by color in four fractions: yellow, brown, orange and ochre. Polyphenol content
      ranged between 396.7 to 1286.7 gallic acid equivalents GAE/100 g pollen; it was
      highest in pollen homogenates obtained with ethanol, followed by those obtained
      with methanol and water. The antioxidant activity ranged from 0.50 to 1.84
      micromoles Trolox equivalents TEAC/100 g for water and ethanol homogenates
      respectively. The results presented in this work suggest that the ethanol extract
      of bee pollen show a potent antioxidant activity, comparable to human plasma,
      probably due to total polyphenol content of bee pollen. This is important because
      the bee pollen would be beneficial not only as a dietary supplement but also as a
      functional food.

PMID- 24020259
TI  - [Physical, chemical and bioactive compounds of tree tomato (Cyphomandra
      betacea)].
AB  - Tree tomato (Cyphomandra betacea) is appreciated for its excellent nutritional
      qualities, being considered a good source of antioxidants compounds, calcium,
      phosphorus, potassium and iron, sugars, organic acids, pectins and flavonoids. In
      this study, were evaluated physical parameters (weight, size, compression
      strength and humidity) and chemical (degrees Brix, titratable acidity, pH,
      protein, dietary fiber, ash, minerals and their bioaccesibility, pectin,
      antioxidants compounds) of the fruit from the Aragua State, Venezuela, as a
      contribution to stimulate and diversify the consumption of the tree tomato. The
      characterization showed that the fruits were at the ripening stage for
      consumption (degrees Brix 10.51, pH 3.5, acidity 0.02 g/100ml and 4.32 Kgf/cm2
      compression strength) gave a yield of 74% pulp. The analytical results of the
      ripped pulp showed a content of 30 Kcal/100 g, dietary fiber (4.10 g/100 g), and
      minerals such as phosphorous, calcium, magnesium, potassium and iron (331.32,
      21.25, 21.18, 17.03 and 7.44 mg/100 g, respectively). Bioaccesibility values of
      6.71 and 1.86% were reported for calcium and iron. The extracted pectin (1.00
      g/100 g) was classified as high methoxyl with high degree of esterification. The
      antioxidant capacity of the ripped pulp (EC50 of 165.00 g/g DPPH and reducing
      power of 0.07 mmol Fe +2/100 g), could be attributed to the presence of ascorbic
      acid (23.32 mg/100 g), lycopene (1.22 mg/100 g), and phenolic compounds (1.39 mg
      GAE/g), anthocyanins (0.29 mg cyanidin/g) and tannins (0.40 mg catechin/100
      g).The results obtained encourage the nutritional benefits and suggest
      applications as a functional ingredient in food product development.

PMID- 24020260
TI  - Volatile composition of peppermint (Mentha piperita L.) commercial teas through
      solid phase extraction.
AB  - Volatiles from aqueous extract of peppermint commercial sachets were investigated
      through gas chromatography/flame ionization detection (GC/FID) and GC/mass
      spectrometry (MS). Samples were prepared under similar conditions as in homemade
      tea. Volatiles were isolated using solid phase extraction method (SPE) with
      Porapak Q trap followed by desorption with acetone. Estimated mean values for
      short and medium chain carboxylic acids (C2-C12) and ketones lay in the range of
      50-64 microg kg(-1) whilst aliphatic alcohols and acyclic hydrocarbons had values
      lower than 6 microg kg(-1). The major volatiles were terpenes (275-382 microg kg(
      1)) that reached 89 % of the total composition. A total of 16 compounds, among
      them dodecane, acetoin, acetol, citral, geraniol and octanoic acid have been
      described by the first time in peppermint tea. These findings could be attributed
      to the different analytical approach employed, mainly to the use of different
      extraction/pre-concentration techniques. Given the apparently lower proportion of
      terpenes in the aqueous extract it may be that the chemical properties of the
      peppermint essential oil are not entirely reproduced with homemade tea.

PMID- 24020261
TI  - Wing shape and size of the western corn rootworm (Coleoptera: Chrysomelidae) is
      related to sex and resistance to soybean-maize crop rotation.
AB  - The western corn rootworm, Diabrotica virgifera virgifera LeConte, is a major
      pest of maize in the United States and more recently, Europe. Understanding the
      dispersal dynamics of this species will provide crucial information for its
      management. This study used geometric morphometric analysis of hind wing venation
      based on 13 landmarks in 223 specimens from nine locations in Illinois, Nebraska,
      Iowa, and Missouri, to assess whether wing shape and size differed between
      rotated and continuously grown maize where crop rotation-resistant and
      susceptible individuals are found, respectively. Before assessing differences
      between rotation-resistant and susceptible individuals, sexual dimorphism was
      investigated. No significant difference in wing (centroid) size was found between
      males and females; however, females had significantly different shaped (more
      elongated) wings compared with males. Wing shape and (centroid) size were
      significantly larger among individuals from rotated maize where crop-rotation
      resistance was reported; however, cross-validation of these results revealed that
      collection site resistance status was an only better than average predictor of
      shape in males and females. This study provides preliminary evidence of wing
      shape and size differences in D. v. virgifera from rotated versus continuous
      maize. Further study is needed to confirm whether wing shape and size can be used
      to track the movement of rotation-resistant individuals and populations as a
      means to better inform management strategies.

PMID- 24020262
TI  - Field-evolved resistance: assessing the problem and ways to move forward.
AB  - "Field-evolved resistance" is defined as a "genetically based decrease in
      susceptibility of a population to a toxin caused by exposure to the toxin in the
      field." The key component of "field-evolved" resistance is that it does confer
      decreased susceptibility to an insecticide in the field. Another key component is
      that the decrease in susceptibility to the insecticide is because of previous
      exposure of the target insect to the toxin in the field. Several studies have
      reported field-evolved resistance to crops engineered to express proteins from
      the bacterium, Bacillus thuringiensis (Bt). However, there has not been a
      consistent standard in the application of the definition of field-evolved
      resistance for Bt crops. The inconsistency in applying the definition arises from
      differences in the methods used to detect resistance, the ecology of the
      interaction between the pest and the Bt crop, and the effective dose the pest
      encounters while feeding on the Bt crop. Using case studies of reported
      resistance to Bt crops, it is demonstrated resistance does not come in a single
      form, and that in most cases, resistance can still be managed.

PMID- 24020263
TI  - A rapid survey technique for Tropilaelaps mite (Mesostigmata: Laelapidae)
      detection.
AB  - Parasitic Tropilaelaps (Delfinado and Baker) mites are a damaging pest of
      European honey bees (Apis mellifera L.) in Asia. These mites represent a
      significant threat if introduced to other regions of the world, warranting
      implementation of Tropilaelaps mite surveillance in uninfested regions. Current
      Tropilaelaps mite-detection methods are unsuitable for efficient large scale
      screening. We developed and tested a new bump technique that consists of firmly
      rapping a honey bee brood frame over a collecting pan. Our method was easier to
      implement than current detection tests, reduced time spent in each apiary, and
      minimized brood destruction. This feasibility increase overcomes the test's
      decreased rate of detecting infested colonies (sensitivity; 36.3% for the bump
      test, 54.2% and 56.7% for the two most sensitive methods currently used in Asia).
      Considering this sensitivity, we suggest that screening programs sample seven
      colonies per apiary (independent of apiary size) and 312 randomly selected
      apiaries in a region to be 95% sure of detecting an incipient Tropilaelaps mite
      invasion. Further analyses counter the currently held view that Tropilaelaps
      mites prefer drone bee brood cells. Tropilaelaps mite infestation rate was 3.5 +/
      0.9% in drone brood and 5.7 +/- 0.6% in worker brood. We propose the bump test
      as a standard tool for monitoring of Tropilaelaps mite presence in regions
      thought to be free from infestation. However, regulators may favor the
      sensitivity of the Drop test (collecting mites that fall to the bottom of a hive
      on sticky boards) over the less time-intensive Bump test.

PMID- 24020264
TI  - Field evaluations of the efficacy of Distance Plus on invasive ant species in
      northern Australia.
AB  - The efficacy of Distance Plus Ant Bait, containing the insect growth regulator
      pyriproxyfen, was tested in the field against two invasive ant species in
      northern Australia: African big-headed ant (Pheidole megacephala (F.)) and yellow
      crazy ant (Anoplolepis gracilipes (Fr. Smith)). Results were also gained for a
      third pest species, Singapore ant (Monomorium destructor (Jerdon)), from one
      trial focused primarily on P. megacephala. Five studies were conducted throughout
      northern Australia, each with different protocols, but common to all was the
      broad-scale dispersal of Distance Plus, coupled with long-term monitoring of ant
      population levels. Additionally, a laboratory trial was conducted to assess if
      there was a direct toxic effect by the bait on A. gracilipes workers, and ant
      community data were collected at some sites in the A. gracilipes trial to assess
      nontarget impacts and subsequent ecological recovery. All three species were
      greatly affected by the treatments. The abundance of P. megacephala declined
      dramatically in all trials, and by the final assessment for each study, very few
      ants remained, with those remaining being attributable to edge effects from
      neighboring untreated properties. At both sites that it occurred, M. destructor
      was initially at least codominant with P. megacephala, but by the final
      assessment, only three M. destructor individuals were present at one lure at one
      site, and only a single individual at the other site. Abundance of A. gracilipes
      fell, on average, to 31% of control levels by 91 d and then slowly recovered,
      with subsequent treatments only providing slightly greater control. No direct
      toxic effect on workers was found in the laboratory trial, indicating that
      population declines of A. gracilipes were typical bait-related declines resulting
      from reduced worker replacement. Nontarget impacts of the bait could not be
      distinguished from the negative competitive impacts ofA. gracilipes, but there
      was a noticeable absence of some key common ant species posttreatment, which was
      more likely the result of baiting rather than competitive exclusion. The species
      composition of treated and untreated sites was statistically indistinguishable in
      multivariate analysis within 2 yr posttreatment, indicating ecological recovery.
      Our findings indicate that Distance Plus has great potential for invasive ant
      management.

PMID- 24020265
TI  - Conversion of high and low pollen protein diets into protein in worker honey bees
      (Hymenoptera: Apidae).
AB  - Adequate protein levels are necessary to maintain strong honey bee [Apis
      mellifera (L.)] colonies. The aim of this study was to quantify how pollens with
      different crude protein contents influence protein stores within individual honey
      bees. Caged bees were fed one of three diets, consisting of high-protein-content
      pollen, low-protein-content pollen, or protein-free diet as control; measurements
      were made based on protein content in hemolymph and fat body, fat body weight,
      and body weight. Vitellogenin in hemolymph was also measured. Bees fed with high
      crude protein diet had significantly higher levels of protein in hemolymph and
      fat bodies. Caged bees did not increase pollen consumption to compensate for the
      lower protein in the diet, and ingesting approximately 4 mg of protein per bee
      could achieve levels of 20 microg/microl protein in hemolymph. Worker bees fed
      with low crude protein diet took more time in reaching similar protein content of
      the bees that were fed with high crude protein diet. The data showed that fat
      bodies and body weight were not efficient methods of measuring the protein status
      of bees. The determination of total protein or vitellogenin concentration in the
      hemolymph from 13-d-old bees and protein concentration of fat bodies from 9-d-old
      bees could be good indicators of nutritional status of honey bees.

PMID- 24020266
TI  - Transmission efficiency of tomato apex necrosis virus by Bemisia tabaci
      (Hemiptera: Aleyrodidae) biotype B in tomato.
AB  - Tomato apex necrosis virus (ToANV) is a new virus that causes important damage in
      tomato crops from the Culiacan Valley, Sinaloa, Mexico. To understand the
      relationship between ToANV and its vector Bermisia tabaci (Hemiptera:
      Aleyrodidae) (Gennadius) biotype B, laboratory and greenhouse trials were
      completed to: 1) determine the acquisition and inoculation access periods of
      ToANV by B. tabaci from tomato to tomato, 2) understand the transmission
      efficiency at different B. tabaci population densities, 3) estimate the time from
      inoculation of the virus at different B. tabaci densities to manifestation of
      symptoms in the plants, and 4) determine the retention time of the virus by the
      insect vector. The presence of the virus in plants was determined by reverse
      transcription-polymerase chain reaction amplification ofa 795-bp fragment
      (GenBank JN704068), which is phylogenetically related to ToANV (GenBank
      EF063242). The results showed that B. tabaci is an effective vector for ToANV
      with relatively long acquisition (12 h) and inoculation (9 h) access periods; a
      single adult is capable of transmitting and retaining the virus for up to 7d,
      suggesting a persistent mode of transmission. These results will help in the
      development of management strategies for controlling the vector and the disease.

PMID- 24020267
TI  - Population dynamics of three aphid species (Hemiptera: Aphididae) on four Ipomoea
      spp. infected or noninfected with sweetpotato potyviruses.
AB  - Three aphid species, Aphis gossypii Glover and Myzus persicae (Sulzer) (efficient
      sweetpotato potyvirus vectors) and Rhopalosiphum padi (L.) (an inefficient
      vector), are commonly found in sweet potato, Ipomoea batatas (L.), in Louisiana.
      Field-grown sweet potatoes are naturally infected with several potyviruses: Sweet
      potato feathery mottle virus, Sweet potato virus G, and Sweet potato virus 2.
      Thus, these aphids commonly encounter virus-infected hosts. What is not known is
      how each of these aphids responds to sweet potato, either infected or virus-free.
      The objectives of this study were to 1) determine if these aphid species can
      colonize mixed virus-infected sweet potato 'Beauregard', and if so, 2) determine
      the effects of virus infection on the population dynamics of each aphid. A.
      gossypii failed to larviposit and R. padi deposited a single nymph that died
      within a day on mixed virus-infected Beauregard. M. persicae larviposited and
      colonized Beauregard and further life-table analyses were warranted. M. persicae
      had a significantly greater reproduction on sweet potato cultivars Beauregard and
      'Evangeline' with mixed virus infection compared with noninfected plants. On
      morning glory species, Ipomoea cordatotriloba (Dennestedt) and Ipomoea hederacea
      (Jacquin), M. persicae had a significantly lower reproduction on Sweet potato
      feathery mottle virus-infected compared with noninfected plants.

PMID- 24020268
TI  - Presence of Dalbulus maidis (Hemiptera: Cicadellidae) and of Spiroplasma kunkelii
      in the temperate region of Argentina.
AB  - "Corn stunt" is one of the main corn (Zea mays L.) diseases in the Americas and
      Dalbulus maidis (DeLong & Wolcott) is the key vector of the pathogen Spiroplasma
      kunkelii Whitcomb. In Argentina, the corn-producing area is in the temperate
      region, where vector and pathogen prevalence levels are unknown. In this study,
      the prevalence and distribution of D. maidis and S. kunkelii in the temperate
      region of Argentina and D. maidis overwintering ability in this region were
      determined. Surveys were conducted in 2005-2006 and 2006-2007 seasons to
      determine D. maidis and S. kunkelii presence, and in winter 2006 to determine the
      vector overwintering ability. The highest S. kunkelii prevalence and incidence
      levels were found in the transition area from the temperate to the subtropical
      region, related to the highest D. maidis prevalence and insects sampled per
      location. D. maidis adults were found in volunteer corn plants and spontaneous
      vegetation in autumn and winter months, which were inoculative for the pathogen
      S. kunkelii. This overwintering ability was related to detection of D. maidis
      insects in corn crops at early growth stages in the following growing season.
      This work emphasizes that corn stunt disease is present in the temperate region
      of Argentina, and this highlights the need to develop proper agronomic practices
      like monitoring insect vector populations and controlling voluntary plants. This
      study also indicates that further research is needed to understand the potential
      yield reduction caused by this pathogen on symptomless plants and population
      dynamics of the insect vector.

PMID- 24020269
TI  - Biological responses of Rhynchophorus ferrugineus (Coleoptera: Curculionidae) to
      Steinernema carpocapsae (Nematoda: Steinernematidae).
AB  - Rhynchophorus ferrugineus (Olivier 1790) (Coleoptera: Curculionidae) is becoming
      a serious problem in Mediterranean areas where it is well-adapted, and now is
      present even in the United States (California). The infestations are primarily in
      urban areas where chemical control is not advisable and million of Euros are
      spent to control it. The effects of the entomopathogenic nematode Steinernema
      carpocapsae (Nematoda: Steinernematidae) on mortality, growth, as well as the
      immune activity of R. ferrugineus larvae, were investigated. R. ferrugineus
      mortality exhibited a positive trend with the dosage and duration of exposure to
      S. carpocapsae. The median lethal dose and median lethal time, important to
      optimize the treatments, were calculated. S. carpocapsae also had a detrimental
      effect on R. ferrugineus weight. In vivo and in vitro effects of S. carpocapsae
      on the phagocytic responses of R. ferrugineus hemocytes also were recorded. S.
      carpocapsae was not encapsulated by R.ferrugineus hemocytes. After 24 h, the
      number of hemocytes recorded in treated larvae was reduced. To investigate the
      defensive abilities of R. ferrugineus humoral and cellular immune systems,
      specifically against the bacterium Xenorhabdus nematophila (Enterobacteraceae),
      the minimum inhibitory concentration that inhibits bacterial growth was measured.
      This is the first time that this technique is applied to entomopathogenic
      bacteria.

PMID- 24020270
TI  - Pesticide compatibility with natural enemies for pest management in greenhouse
      gerbera daisies.
AB  - Pesticides commonly used in commercial greenhouse management were evaluated for
      compatibility with two biological control agents: a leafminer parasitoid
      (Diglyphus isaea [Walker]), and a predatory mite (Neoseiulus californicus
      [McGregor]). These natural enemies were exposed to miticides, fungicides, and
      insecticides targeting leafminers, thrips, and whiteflies, according to label
      directions in laboratory vial assays, after which mortality at 12, 24, and 48 h
      was recorded. Greater mortality of predatory mites than leafminer parasitoids was
      observed overall, illustrating that fewer pesticides were compatible with
      predatory mites compared with the parasitoid. However, some commonly used
      pesticides were found to cause high mortality to both the leafminer parasitoid
      and predatory mites. Twospotted spider mite (Tetranychus urticae Koch)
      infestations often disrupt leafminer (Liriomyza trifolii [Burgess]) biocontrol
      programs. Therefore, potentially compatible miticides (bifenazate, hexythiazox,
      spiromesifen, acequinocyl, etoxazole, and clofentezine) identified in laboratory
      trials were also evaluated in a greenhouse study and found to be compatible with
      leafminer biocontrol.

PMID- 24020271
TI  - Beauveria bassiana (Ascomycota: Hypocreales) wound dressing for the control of
      Euzophera pinguis (Lepidoptera: Pyralidae).
AB  - Injury to olive tree trunks and branches because of biotic and abiotic factors,
      such as pruning and mechanical harvesting, attracts the olive pyralid moth
      Euzophera pinguis Haworth (Lepidoptera: Pyralidae). This moth has become
      increasingly important in the Mediterranean region during recent years. The use
      of an entomopathogenic fungus for wound dressing for pest control is reported for
      the first time in this study. Beauveria bassiana (Ascomycota: Hypocreales) strain
      EABb 08/04-Ep was originally obtained from a diseased E. pinguis larva and has
      shown effective E. pinguis control in an olive crop in Jaen, Andalusia, Spain,
      under field conditions during the spring and fall of 2008 and 2009 and the spring
      of 2011. Experimental artificial 30 by 30-mm square wound cages were large enough
      to allow the E. pinguis females to oviposit. Approximately 80 and 40-60% of the
      control wounds contained live larvae in the experiments that occurred during the
      spring and fall, respectively. The B. hassiana wound dressing gave similar
      results as the chlorpyrifos wound dressing throughout the experiment, with
      efficacies reaching 80-85% in the spring and 90-95% in the autumn. The B.
      bassiana fungus was recovered from 60-90% of the wounds at the completion of the
      experiments and after 60 d of treatment. These data indicate that strain EABb
      08/04-Ep applied to the pruning wounds can be an effective tool for the microbial
      control of E. pinguis in olive crops. Moreover, B. bassiana may be used within
      integrated pest management strategies to minimize chemicals, depending on the
      population density of the pyralid moth.

PMID- 24020272
TI  - Development of phytosanitary cold treatments for oranges infested with Bactrocera
      invadens and Bactrocera zonata (Diptera: Tephritidae) by comparison with existing
      cold treatment schedules for Ceratitis capitata (Diptera: Tephritidae).
AB  - Phytosanitary cold treatments were tested for Bactrocera invadens Drew, Tsuruta,
      and White and Bactrocera zonata (Saunders) using comparisons with Ceratitis
      capitata (Wiedemann). Oranges were infested by puncturing holes in the peel and
      allowing tephritids to oviposit in the holes. The treatments were initiated when
      the larvae reached late third instar because previous research had shown that
      stage to be the most cold tolerant for all three species. Results show that B.
      invadens is not more cold tolerant than C. capitata and B. zonata at 1.0 +/- 0.1
      degrees C and lend support to the use of C. capitata cold treatment schedules for
      B. invadens. It cannot be concluded that B. zonata is not more cold tolerant than
      C. capitata.

PMID- 24020274
TI  - Frequency and distribution of extended diapause in Nebraska populations of
      Diabrotica barberi (Coleoptera: Chrysomelidae).
AB  - The frequency of extended diapause in populations of the northern corn rootworm,
      Diabrotica barberi Smith & Lawrence (Coleoptera: Chrysomelidae), was measured in
      eastern Nebraska. Adult collections were made during late summer in 2008 and 2009
      from eight sites each year (seven sites were consistent over years). Eggs were
      obtained from 12 to 20 females per site and were held on moist soil under
      appropriate temperature profiles to facilitate egg survival, diapause
      development, and diapause termination. Percentage egg hatch was recorded after
      the first and second year for the 2008 and 2009 collections. Additional extended
      diapause expression was estimated for the 2008 and 2009 collections by counting
      remaining live eggs after the second-year egg hatch was completed. These data
      also were used to estimate each site's maximum egg viability. Results
      collectively indicate that the extended diapause trait was present in all eastern
      Nebraska populations; however, significant variation in the frequency of extended
      diapause was observed within and among D. barberi populations (first-year mean
      percentage egg hatch range: 2008 collections: 4.5-38.6%; 2009 collections: 10.7
      42.5%). Geographically, the highest incidence of extended diapause was found
      along a north-south transect in eastern counties of Nebraska that parallels the
      Missouri River. In general, the frequency of extended diapause was lower in sites
      found west of the north-south transect. This study contributes to the knowledge
      base needed to develop appropriate D. barberi management strategies in Nebraska.
      These data can be used to pinpoint areas of Nebraska that may have the greatest
      risk of economic injury in first-year corn (Zea mays L.) when D. barberi
      densities are high.

PMID- 24020273
TI  - Effects of phosphine fumigation on survivorship of Epiphyas postvittana
      (Lepidoptera: Tortricidae) eggs.
AB  - Light brown apple moth, Epiphyas postvittana (Walker), eggs were subjected to
      phosphine fumigations under normal atmospheric and elevated oxygen levels in
      laboratory-scale chamber experiments to compare their susceptibilities to the two
      different fumigation methods. In fumigations conducted under atmospheric oxygen
      at 5 and 10 degrees C, egg survivorship decreased with increase in phosphine
      concentration but then increased at a concentration of 3,000 ppm; this increase
      was significant at 10 degrees C. Based on egg survivorship data, phosphine
      fumigations conducted in a 60% oxygen atmosphere were significantly more
      effective than those conducted under atmospheric oxygen conditions. Oxygenated
      phosphine fumigations at 5 and 10 degrees C killed all 1,998 and 2,213 E.
      postvittana eggs treated, respectively, after 72 h of exposure. These results
      indicate the great potential of oxygenated phosphine fumigation for the control
      of E. postvittana eggs.

PMID- 24020275
TI  - Gall development and clone dynamics of the galling aphid Schlechtendalia
      chinensis (Hemiptera: Pemphigidae).
AB  - The aphid Schlechtendalia chinensis (Bell) induces galls on its primary host,
      Rhus chinensis Mill. We studied temporal changes in gall and aphid clonal
      population size throughout the period of gall development. Gall-size changes
      occurred in four stages: a first slow growth period, a fast growth period, a
      second slow growth period, and a growth reduction period. Gall volume and surface
      area increased abruptly toward the end of July, peaking during October, in
      parallel with an increase in aphid clonal population size, from one individual to
      > 10,000 aphids per gall. Clear changes were seen in the clone dynamics of S.
      chinensis. Fundatrix began to produce first-generation apterous fundatrigenia
      during late May to early June. Second-generation apterous fundatrigenia appeared
      at the start of July. Alate fundatrigeniae with wing pads first appeared at the
      end of August, but accounted for < 1% of the individuals in the galls. Adult
      alate fundatrigeniae first appeared at the start of October. Abrupt changes in
      aphid density and crowding might trigger the induction of alate morphs in the
      galls. Of the eight gall properties that we recorded, gall volume was the most
      accurate measure of gall fitness.

PMID- 24020276
TI  - Biology and developmental strategies of the Palaearctic parasitoid Bracon
      nigricans (Hymenoptera: Braconidae) on the neotropical moth Tuta absoluta
      (Lepidoptera: Gelechiidae).
AB  - During the years after the invasion of Western Palaearctic tomato crops by the
      South American tomato leafminer, Tuta absoluta (Meyrick) (Lepidoptera:
      Gelechiidae), several indigenous generalist parasitoids have been recorded on
      this new host. Among these, Bracon nigricans Szepligeti (Hymenoptera: Braconidae)
      is widely distributed in the Palaearctic region, and has been frequently
      recovered from South American tomato leafminer. However, most of the available
      data on this species deal with taxonomic aspects and its recovery in faunistic
      surveys. The current study documents the biology of B. nigricans on South
      American tomato leafminer, and provides a scientific basis for its inclusion in
      South American tomato leafminer management programs in Afro-Eurasia. We studied
      several B. nigricans life-history traits relevant to juvenile development and
      reproduction by females. B. nigricans proved to be an idiobiont and a synovigenic
      ectoparasitoid of mature South American tomato leafminer larvae. Several B.
      nigricans reproductive traits were influenced by the age of the mothers; on
      average, the progeny had a slightly male-biased sex ratio (60% males) and a low
      rate of successful development (37%). Adult females lived 42.8 d and produced an
      average of 29.8 offspring. These biological parameters yielded an intrinsic rate
      of increase of 0.052. Females showed behavioral plasticity in host use, as
      initial host paralysis was followed by host-feeding, oviposition, or host
      rejection, with a consequent high mortality rate among hosts exposed to
      parasitism. Although further field studies are needed, these data, obtained in
      laboratory conditions, suggest that B. nigricans should be considered as a
      potential biological control agent of in newly invaded areas of the Palaearctic
      region.

PMID- 24020277
TI  - The susceptibility of different pepper varieties to infestation by Bactrocera
      latifrons (Diptera: Tephritidae).
AB  - The Malaysian fruit fly, Bactrocera latifrons (Hendel), is a pest of peppers
      (Capsicum spp.) in Thailand. A field trial was undertaken to determine whether
      five commonly used cultivars of C. annuum, with marked differences in morphology
      and pungency, varied in their susceptibility to infestation by B. latifrons.
      Experiments carried out in both the dry and rainy seasons showed temporal
      differences in the number of fruits per cultivar, but there was no effect of
      variety or season on the proportion of fruits attacked or the number of pupae
      obtained per infested fruit However, the number of dead larvae per infested fruit
      was significantly higher, and the percent of pupae giving rise to adults was
      lower for the larger sweet pepper than other cultivars tested.

PMID- 24020278
TI  - EAG responses of Apis cerana to floral compounds of a biodiesel plant, Jatropha
      curcas (Euphorbiaceae).
AB  - The Eastern honey bee, [Apis cerana (F.)], is an important and common pollinator
      for an important biodiesel tree, [Jatropha curcas (L.)]. To understand
      sensitivity of A. cerana to different floral compounds, we quantified volatile
      floral compounds of J. curcas, then determined electroantennogram (EAG) responses
      of A. cerana to 11 compounds each at five doses (0.4, 4, 40, 400, and 4,000
      microg) of six most active floral compounds. Our results demonstrated that floral
      compounds of J. curcas differ in variety and quantity while linalool is always a
      major constituent in floral blends from three different plantations. Antennae of
      A. cerana responded to all 11 floral compounds, implying a broad sensitivity of
      A. cerana to different floral compounds of J. curcas. Antennae of A. cerana were
      most sensitive to six compounds, including all aldehydes (decanal, hexanal,
      nonanal, and octanal), linalool, and an alcohol (3-hexenol), suggesting that A.
      cerana possesses chemoreceptors to aldehydes, linalool, and alcohol on the
      antenna. Furthermore, low doses elicited a zero EAG response and high doses a
      positive one under all of six most active compounds. Thus, EAG responses of A.
      cerana were both chemical specific and dose-dependent. Our results here suggest
      that A. cerana is senstive to various floral compounds, and linalool in the
      floral blends of J. curcas plays a key role to attract A. cerana.

PMID- 24020279
TI  - Ex-ante determination of the capacity of field tests to detect effects of
      genetically modified corn on nontarget arthropods.
AB  - Field trials may be required to assess risks of genetically modified crops (GMCs)
      for nontarget arthropods. One critical point of these trials is their capacity to
      detect differences between the density of one taxon in the GMC and that in the
      comparator. The detection capacity of a trial depends on the abundance and
      variability of the taxon, the values assumed for type I (alpha) and II (beta)
      errors, and the characteristics of the trial and statistical design. To determine
      the optimal trial layout and statistical analysis, 20 field trials carried out in
      Spain from 2000 to 2009 to assess risks of GMCs on nontarget arthropods were
      examined with alpha and beta fixed at 0.05 and 0.20, respectively. Under the
      experimental conditions tested, taxon variability is the most influential
      component determining test detection capacity; the maximum acceptable values of
      taxon variability to achieve a certain detection capacity were calculated for
      different numbers of replicates (blocks), treatments, and years. A close
      relationship between taxon variability and mean abundance in visual counts,
      pitfall traps, and yellow sticky traps allowed minimal critical abundance
      thresholds to be estimated to guarantee a certain detection capacity and to
      establish abundance criteria for selecting focal taxa. The number of replications
      (blocks), treatments, sites, and years has a lesser influence on detection
      capacity once minimal values in taxon abundance in field trials are ensured.
      Conclusions reached on the detection capacity of field trials with the
      experimental data obtained under Mediterranean conditions should be contrasted
      with those of other regions.

PMID- 24020280
TI  - Corn stand and yield loss from seedling injury by southern corn rootworm
      (Coleoptera: Chrysomelidae).
AB  - Southern corn rootworm, Diabrotica undecimpunctata howardi Barber, can cause
      severe stand loss in reduced tillage corn after a vetch cover crop. Trials
      conducted over 3 yr found that clothianidin and thiamethoxam neonicotinoid seed
      treatments and conventional granular insecticides applied in-furrow or as a T
      band were very effective against southern corn rootworm. Treatments were
      categorized as no control (untreated), partial control, and full control based on
      the extent of seedling injury. In 2 yr, damaged plants were individually marked
      and their survival, tiller (i.e., secondary stem) production, and ear and grain
      weight measured. About one-half of plants injured by larvae produced a tiller,
      with most plants producing tillers within 30 d after planting. All dead-hearted
      plants not producing a tiller died and were not evident by mid-season. In no
      control plots with severe damage, healthy plants produced more ears per plant and
      secondarily more grain weight per plant than healthy plants in full control
      plots. Plants with early tillers in no control produced approximately 38% of the
      grain weight of healthy plants compared with only approximately 6% in full
      control plots, whereas plants with late tillers in no control plots produced <
      10% of the grain weight of healthy plants and produced no grain in full control
      plots. Therefore, in stands with severe seedling damage, remaining healthy plants
      and damaged plants producing a tiller within 30 d of planting responded to lower
      plant population by producing more ears and grain per plant. However, in full
      control plots with low levels of damage, damaged plants producing a tiller often
      persisted until harvest but produced very little grain thereby acting as weeds
      with the stand.

PMID- 24020281
TI  - Reduction of soybean yield components by Megacopta cribraria (Hemiptera:
      Plataspidae).
AB  - ABSTRACT Since its discovery in the United States, the invasive plataspid
      Megacopta cribraria (F.) (Hemiptera: Plataspidae) has infested soybean [Glycine
      max (L.) Merrill] fields in often alarming numbers in parts of the southeastern
      United States. Although a known feeder on soybean, reports of its pest status in
      its native Asian range are conflicting, and little information exists documenting
      its impact on soybean yields. Our objective was to examine the relationship
      between M. cribraria density and soybean yield loss. M. cribraria adults and
      nymphs were confined to small soybean plots by using walk-in field cages from
      late vegetative stage to harvest in 2011 and 2012. Adults (0, 5, or 25 per plant)
      were added at late vegetative stages, and their progeny were allowed to complete
      a full generation within the caged plots. Densities reached as high as 182.5 +/-
      23.1 (SEM) nymphs and adults per plant, and soybean yield was reduced by as much
      as 59.6% at the highest density treatment. The yield components seeds per pod and
      individual seed weight were reduced as M. cribraria densities increased, but pods
      per plant and protein and oil content were not affected. Preliminary economic
      injury level curves for a range of grain prices and management costs were
      calculated based on 2012 yield loss data combined with population monitoring. M.
      cribraria is capable of causing severe reductions in soybean yields at densities
      that are relevant within its invasive U.S. range.

PMID- 24020282
TI  - Trap lure blend of pine volatiles and bark beetle pheromones for Monochamus spp.
      (Coleoptera: Cerambycidae) in pine forests of Canada and the United States.
AB  - In 2007-2008, we examined the flight responses of Monochamus titillator (F.)
      complex [M. titillator, Monochamus carolinensis (Olivier), and any possible
      hybrids], Monochamus scutellatus (Say), Monochamus clamator (LeConte), Monochamus
      obtusus Casey, and Monochamus mutator LeConte (Coleoptera: Cerambycidae) to
      multiple-funnel traps baited with and without host volatiles and bark beetle
      pheromones. Experiments were conducted in mature pine (Pinus) stands in Alberta
      (Canada), and Arkansas, Arizona, California, Florida, Idaho, Michigan, Montana,
      New Hampshire, North Carolina, Ohio, Oregon, Tennessee, Utah, and Wisconsin
      (United States). At each location, traps were deployed in 10 replicate blocks of
      four traps per block. The trap treatments were: 1) blank control; 2) ipsenol and
      ipsdienol; 3) ethanol and alpha-pinene; and 4) a quaternary blend of ipsenol,
      ipsdienol, ethanol, and alpha-pinene. All five species or species complex of
      Monochamus preferred traps baited with the quaternary blend over all other
      treatments. The consistency of these results across such a large geographic area
      suggests that similar selection pressures may be acting on Monochamus spp. in
      pine forests, regardless of variation in stand composition and climatic
      conditions. Our results suggest that multiple-funnel traps baited with the
      quaternary blend ofipsenol, ipsdienol, ethanol, and alpha-pinene may be highly
      effective for monitoring various Monochamus spp. in pine forests of North
      America, and may have utility in trapping and detection programs in North America
      and overseas.

PMID- 24020283
TI  - Evaluation of screen barriers on redbay trees to protect them from Xyleborus
      glabratus (Coleoptera: Curculionidae: Scolytinae) and distribution of initial
      attacks in relation to stem moisture content, diameter, and height.
AB  - Fine mesh screen was used to create a physical barrier to prevent redbay ambrosia
      beetles, Xyleborus glabratus Eichhoff (Coleoptera: Curculionidae: Scolytinae),
      from accessing various parts of the boles of redbay trees, Persea borbonia (L.)
      Sprengel, and infecting them with the laurel wilt fungus, Raffaelea lauricola
      (T.C. Harrington, Fraedrich, & Aghayeva). Screen barriers prevented beetles from
      attacking boles of mature redbay trees from the ground to 1 or to 3 m and from 1
      to 3 m above ground. Untreated control trees were sampled more extensively to
      determine how location of initial attacks varied with height, diameter, and
      moisture content of the wood. Screening did not affect tree survival, and all of
      the trees died within 243 d from the beginning of observation. Initial points of
      attack by X. glabratus varied from ground level to heights of at least 6.6 m.
      Trees showed characteristic laurel wilt symptoms with as few as two X. glabratus
      entry points. The number of attacks exhibited nonlinear relationships with
      diameter (P = 0.0004; r2 = 0.82) and height (P = 0.0013; r2 = 0.69) but were not
      correlated with moisture content. Attacks increased gradually with increasing
      stem diameter up to approximately 10 cm after which the attacks became more
      numerous. X. glabratus attacks were most numerous on the tree bole near the
      ground. Attacks then declined as tree height reached 2-3 m. From 3 to 8 m,
      attacks were relatively consistent.

PMID- 24020284
TI  - A repellent net as a new technology to protect cabbage crops.
AB  - Floating row covers or insect-proof nets with fine mesh are effective at
      protecting vegetable crops against aphids but negatively impact plant health,
      especially under warm conditions. Furthermore, in control of cabbage insect
      pests, aphid parasitoids cannot enter the fine-mesh nets, leading to frequent
      aphid outbreaks. To surmount these difficulties, a 40-mesh-size repellent net
      treated with alphacypermethrin was studied in laboratory and field tests. Results
      showed both irritant and repellent effects of the alphacypermethrin-treated net
      on Myzus persicae (Sulzer) (Hemiptera: Aphididae) and its parasitoid Aphidius
      colemani (Haliday) (Hymenoptera: Braconidae). Under field conditions, there were
      no pests on cabbage protected with the repellent net. The repellent net allowed
      combining a visual and repellent barrier against aphids. Because of this additive
      effect, repellent nets allowed covering cabbage permanently with adequate
      protection against all pests.

PMID- 24020285
TI  - Binomial and enumerative sampling of Tetranychus urticae (Acari: Tetranychidae)
      on peppermint in California.
AB  - The two-spotted spider mite, Tetranychus urticae Koch, is an economic pest on
      peppermint [Mentha x piperita (L.), 'Black Mitcham'] grown in California. A
      sampling plan for T. urticae was developed under Pacific Northwest conditions in
      the early 1980s and has been used by California growers since approximately 1998.
      This sampling plan, however, is cumbersome and a poor predictor of T. urticae
      densities in California. Between June and August, the numbers of immature and
      adult T. urticae were counted on leaves at three commercial peppermint fields
      (sites) in 2010 and a single field in 2011. In each of seven locations per site,
      45 leaves were sampled, that is, 9 leaves per five stems. Leaf samples were
      stratified by collecting three leaves from the top, middle, and bottom strata per
      stem. The on-plant distribution of T. urticae did not significantly differ among
      the stem strata through the growing season. Binomial and enumerative sampling
      plans were developed using generic Taylor's power law coefficient values. The
      best fit of our data for binomial sampling occurred using a tally threshold of T
      = 0. The optimum number of leaves required for T urticae at the critical density
      of five mites per leaf was 20 for the binomial and 23 for the enumerative
      sampling plans, respectively. Sampling models were validated using Resampling for
      Validation of Sampling Plan Software.

PMID- 24020286
TI  - Seasonal biology of Ferrisia gilli (Hemiptera: Pseudococcidae) in California
      Sierra foothill vineyards.
AB  - The mealybug Ferrisia gilli Gullan is an emerging pest of wine grapes grown in
      California's Sierra foothills. A relatively new species, it had previously been
      recorded as a pest of pistachio, almond, and ornamentals. It was first reported
      on grape in El Dorado County in 2003 and has since established and spread.
      Nondestructive monitoring of grape vine sections was conducted in untreated
      vineyard plots and compared with destructive sampling conducted in grower-treated
      plots in 2008 and 2009 to determine F. gilli life stage seasonal presence, number
      of generations, location on the vine during the season, and damage potential to
      fruit clusters. Two generations were observed to be completed during the season.
      F. gilli overwintered under the bark at the base of the trunk, trunk, and cordon
      as second and third instars. Adults were found at the base of emerging shoots
      (spring) or on and under bark of old and new spurs. Live crawlers were born in
      June (first generation) and late August to September (second generation), and
      migrated to leaves to feed before moving to protected locations under bark or
      into fruit clusters. Lower mealybug densities and fruit damage were recorded on
      vines with than without insecticide treatment(s). Parasitized mealybugs were
      collected in low numbers and an Acerophagus sp. was the dominant parasitoid.

PMID- 24020287
TI  - Diel activity and behavior of Bagrada hilaris (Hemiptera: Pentatomidae) on desert
      cole crops.
AB  - Patterns of diel activity and behavior of the Bagrada bug, Bagrada hilaris
      (Burmeister) (Hemiptera: Pentatomidae), were investigated in a series of field
      and greenhouse experiments in Yuma, AZ. Adults of B. hilaris were monitored by on
      site direct observation on broccoli and cauliflower plants in large-block
      experimental plots at various intervals throughout consecutive 24-h periods. In
      the field trials, mean number of B. hilaris adults differed among sampling times,
      with peak abundance observed consistently between 1300 and 1800 hours. There was
      a positive correlation between temperature and numbers ofB. hilaris adults in all
      fields, and a negative relationship between humidity and adult numbers in 7 of 12
      fields. Significant relationships between temperature and B. hilaris numbers were
      revealed in regression models for all trials. Slopes were not significantly
      different among all broccoli blocks or in three of the four cauliflower fields.
      In greenhouse studies, mating occurred throughout the day but peaked between 1000
      and 1600 hours. Females of B. hilaris caused more feeding damage than males on
      the first true leaf of broccoli, and additional differences in behavior between
      sexes were observed. Our results suggest that higher temperatures increase field
      activity and influence the behavior of adult B. hilaris, and temperature is a
      more reliable indicator to predict the activity of B. hilaris than other
      environmental parameters measured. The implications of these findings for
      developing monitoring and management programs for B. hilaris in cruciferous crops
      are discussed.

PMID- 24020288
TI  - Advances in the use of trapping systems for Rhynchophorus ferrugineus
      (Coleoptera: Curculionidae): traps and attractants.
AB  - Given the social importance related to the red palm weevil, Rhynchophorus
      ferrugineus Olivier (Coleoptera: Curculionidae), efforts are being made to
      develop new control methods, such as the deployment of trapping systems. In this
      work, the efficacy of a new black pyramidal trap design (Picusan) has been
      verified in comparison with white and black buckets. In addition, the attractant
      and synergistic effect of ethyl acetate (EtAc) at different release levels has
      been evaluated under field conditions. The results show that Picusan traps
      captured 45% more weevils than bucket-type traps, offering significantly better
      trapping efficacy. The addition of water to traps baited with palm tissues was
      found to be essential, with catches increasing more than threefold compared with
      dry traps. EtAc alone does not offer attractant power under field conditions, and
      the release levels from 57 mg/d to 1 g/d have no synergistic effect with
      ferrugineol. Furthermore, significantly fewer females were captured when EtAc was
      released at 2 g/d. The implications of using EtAc dispensers in trapping systems
      are discussed.

PMID- 24020289
TI  - Life history, natural enemies, and management of Disholcaspis quercusvirens
      (Hymenoptera: Cynipidae) on live oak trees.
AB  - Live oak (Quercus virginiana Mill.) trees are hosts to a complex of gall making
      arthropods. However, the bullet galls produced by the asexual generation of the
      cynipid Disholcaspis quercuscirens (Ashmead) can esthetically and physically
      damage nursery and street trees, and thus reduce tree value. We sought to
      describe the unknown sexual generation of D. quercusvirens, describe the
      development of galls from both generations, record adult cynipid and parasitoid
      activity periods, and evaluate the efficacy of several insecticides to suppress
      the gall makers and prevent additional gall formation. The oviposition period for
      asexual females occurred from late November to January in both years of the
      caging study. Eggs laid into dormant buds resulted in small bud galls in which
      the sexual generation developed for 4-5 mo. Sexual adults emerged and laid eggs
      in young elongating shoots in April. Bullet galls began protruding from branches
      in June, and asexual wasps emerged 5-7 mo later. Cynipids that emerged from the
      bullet (asexual generation) and bud (sexual generation) galls were genetically
      identical. Both generations were heavily parasitized. Targeting asexual females
      with an early December treatment of bifenthrin or acephate significantly reduced
      the number of bud galls, but control did not extend to the next generation of
      bullet galls, possibly because of reinvasion from neighboring infested trees.

PMID- 24020290
TI  - Effect of Tetranychus urticae (Acari: Tetranychidae), on marketable yields of
      field-grown strawberries in north-central Florida.
AB  - Understanding the impact of a pest species on a particular crop is critical for
      the success of a pest management program. Field studies were conducted to
      determine the effect of the twospotted spider mite, Tetranychus urticae Koch, on
      marketable yield of strawberries during the 2008/2009 and 2009/2010 growing
      seasons. Low, medium, and high mite infestation levels were established by
      initial inoculations of5, 10, and 20 twospotted spider mites per strawberry leaf,
      respectively. A control treatment maintained at near zero mites through
      applications of an acaricide, bifenazate (Acramite 50 WP), was also included.
      Weekly records of motile twospotted spider mites were obtained over 13 and 16 wk
      during the 2008/2009 and 2009/2010 growing seasons, respectively. Degree-days and
      weather parameters were monitored to determine their effect on mite population.
      In addition, mite-days were calculated for each year from weekly mite counts to
      determine the effect of mites on marketable yield of strawberries. In both years,
      twospotted spider mite population increased throughout the growing seasons. More
      degree-days were accumulated during the 2008/2009 growing season, and mite
      population was higher in 2008/2009 than in 2009/2010. Mite population density per
      leaf increased up to 278 motiles per leaf in 2008/2009 growing season as compared
      with 137 in 2009/2010 within the high-infestation-level treatment. The divergence
      in mite population between the two growing seasons was attributed mainly to
      temperature differences between the two seasons that affected mite population
      development and establishment. During both growing seasons, the high mite
      infestation level had lowest marketable yield. A negative correlation between
      cumulative mite-days and harvested marketable yields was detected in both
      seasons, but it was only significant during the 2008/2009 growing season.
      Strawberry yield reduction was detected when plants attained 80 mites per leaf in
      2008/2009 and 50 mites per leaf in 2009/2010 within the high mite infestation
      treatment. Factors that affect mite population establishment and management for
      twospotted spider mites on strawberries are discussed.

PMID- 24020291
TI  - Oviposition efficacy of Drosophila suzukii (Diptera: Drosophilidae) on different
      cultivars of blueberry.
AB  - Drosophila suzukii (Matsumura) is an important pest of thin-skinned fruits
      including blueberry, raspberry, strawberry, and cherry. Blueberry was introduced
      into Japan in the 1950s, and severe economic losses attributable to D. suzukii
      were first reported in 2002. The objective of this study was to elucidate whether
      oviposition behavior varies among blueberry cultivars having different firmness
      of fruit. Fruit firmness in 12 cultivars of highbush blueberry (Vaccinium
      corymbosum L.) and rabbiteye blueberry (Vaccinium virgatum Aiton) was determined
      using a rheometer. More eggs tended to be laid in berries of cultivars possessing
      softer fruits than in those having firmer fruits. Choice tests, where one female
      was allowed to oviposit on blueberry fruits with different firmness, showed that
      softer fruits were more vulnerable to D. suzukii females than firmer fruits.

PMID- 24020292
TI  - Neem derivatives are not effective as toxic bait for tephritid fruit flies.
AB  - Neem derivatives have been widely touted as replacements for pesticides. A
      feasible replacement of synthetic insecticides in the management of fruit flies
      could be to use neem products in baits. This study evaluated the bioactivity of
      neem (Azadirachta indica A. Juss) derivatives in bait for adults of Anastrepha
      fraterculus (Wiedemann) and Ceratitis capitata (Wiedemann). The estimated LCs50
      values for A. fraterculus and C. capitata were 7,522 ppm (18.40 ppm of
      azadirachtin) and 1,368 ppm (3.35 ppm of azadirachtin), respectively, using an
      aqueous extract of neem seeds in bait after 10 d of experimentation. No
      significant differences in the mortality of A. fraterculus and C. capitata adults
      exposed to baits made from different extracts and neem oil were observed after 3
      h or 2 or 6 d; differences among the treatments were observed only on the 10th
      day of the evaluation. We conclude that neem derivatives applied as a bait spray
      over citrus plants did not demonstrate a toxic effect on A. fraterculus and C.
      capitata. The reasons for the low efficacy of the neem bait on Tephritid fruit
      flies are discussed.

PMID- 24020293
TI  - Monitoring attack and flight activity of Xylosandrus spp. (Coleoptera:
      Curculionidae: Scolytinae): the influence of temperature on activity.
AB  - Wood-boring ambrosia beetles (Coleoptera: Curculionidae: Scolytinae), including
      Xylosandrus spp., are key pests in ornamental nurseries. Knowledge of their
      activity in spring is important for nursery growers to effectively time their
      protective sprays. We measured the reliability of ethanol-baited bottle traps for
      monitoring emergence of overwintered Xylosandrus spp. in ornamental nurseries.
      Detection of initial flight activity by traps was compared with initial attacks
      on ethanol-injected trap trees. To develop tools for forecasting Xylosandrus
      germanus (Blandford) activity, the relationships between temperature and their
      attack and flight activity were examined, and the bloom sequence of ornamental
      plants was examined as phenological indicators of X. germanus emergence in Ohio.
      Captures of X. germanus coincided with attacks on trap trees on seven of eight
      occasions over 2 yr in four nurseries. Xylosandrus crassiusculus (Motshulsky)
      were detected in only one nursery and captures coincided with attacks each year.
      There was a strong relationship between maximum daily temperatures 20 and
      21degrees C and X. germanus attack and flight activity. No attack or flight
      activity were detected in a monitoring period unless there were 1 or 2 d of at
      least 20 degrees C. Emergence of X. germanus always began after and within 6 d of
      full bloom on Cornelian cherry dogwood, and usually after and within 4 d of first
      bloom on Norway maple and full bloom on border forsythia. The traps or
      phenological indicators can be used by growers to monitor emergence of X.
      germanus to time their initial protective sprays. The relationship between X.
      germanus activity and temperature can be used by growers to make decisions on
      timing subsequent treatments.

PMID- 24020294
TI  - Delayed toxicity of two chitinolytic enzyme inhibitors (psammaplin a and
      pentoxifylline) against eastern subterranean termites (Isoptera:
      Rhinotermitidae).
AB  - By using a no-choice feeding bioassay, delayed toxicity and concentration
      dependent mortality of two chitinolytic enzyme inhibitors, pentoxifylline and
      psammaplin A, were evaluated by determining LT50, LT90, and LT99 (lethal time)
      against the economically important eastern subterranean termite, Reticulitermes
      flavipes (Kollar). Pentoxifylline- and psammaplin A-incorporated diets (filter
      paper) were assayed at 0.01, 0.02, 0.04, 0.08, and 0.21% and 0.0375, 0.075, 0.15,
      and 0.3% active ingredient (wt:wt), respectively. Acetone-only treated filter
      paper served as diet for the control treatments. Termite workers were allowed to
      feed on diet until 100% test population mortality occurred (80-95 d). Both
      chitinase inhibitors were shown to be toxic to R. flavipes. Concentration
      dependent toxicity occurred within the pentoxifylline treatments over the range
      of 0.01-0.08%, with 0.08% treatments producing an LT50 of 32.2 d. However,
      mortality in response to psammaplin A treatments lacked concentration-dependent
      toxicity. Treatment with 0.3% psammaplin A produced an LT50 of 21.3 d. Mortality
      in response to lower psammaplin A treatments displayed no concentration-dependent
      trends. This study provides the first report on delayed toxicity of chitinolytic
      enzyme inhibitors against eastern subterranean termites (order Isoptera) and
      toxicological data on pentoxifylline and psammaplin A over a range of
      concentrations.

PMID- 24020295
TI  - Feeding response of subterranean termites Coptotermes curvignathus and
      Coptotermes gestroi (Blattodea: Rhinotermitidae) to baits supplemented with
      sugars, amino acids, and cassava.
AB  - Feeding responses of subterranean termites Coptotermes curvignathus (Holmgren)
      and Coptotermes gestroi (Wasmann) (Blattodea: Rhinotermitidae) to bait matrices
      supplemented with various sugars, amino acids, and cassava were evaluated both in
      the laboratory and field. The results indicated that the two termite species
      consumed significantly different amount of filter papers that had been treated
      with various types and concentrations of sugars and amino acids. Based on
      consumption and survival data, filter papers with 3% glucose and 3% xylose were
      among the most consumed by C. curvignathus and C. gestroi, respectively. Both
      termite species consumed more of the filter papers treated with 3% casein than
      filter papers treated with L-alanine. Both species had a comparable survival rate
      compared with those in the controls. Results from laboratory and field trials on
      bait prototypes indicated that C. gestroi consumed more bait prototypes
      containing cellulose, 3% xylose, 3% casein, and cassava, whereas C curvignathus
      consumed more bait prototype containing cellulose, 3% glucose, and cassava, than
      on pure crystalline cellulose baits. Thus, with an improved and cost-effective
      bait formulation, a much wider control of subterranean termite colonies could be
      achieved.

PMID- 24020296
TI  - Effect of trap design, chemical lure, carbon dioxide release rate, and source of
      carbon dioxide on efficacy of bed bug monitors.
AB  - Bed bugs, (Cimex lectularius L.), are difficult to find because of their
      nocturnal and secretive behavior. In recent years, a number of monitors
      containing carbon dioxide (CO2), chemical lures, heat, or both, to attract bed
      bugs have been developed for detecting bed bugs. Ineffective trap design, lack of
      attraction of chemical lures, high cost of the CO2 delivery system, or
      insufficient CO release rates are some factors that limited the wide adoption of
      these monitors. To develop an affordable and effective monitor, we conducted a
      series of laboratory and field tests. Specifically, we tested a new pitfall trap
      design, a chemical lure mixture, different CO2 release rates, and a sugar and
      yeast mixture as CO2 source. Results show the new pitfall trap design was
      significantly more effective than Climbup insect interceptor, the most effective
      passive monitor available in the market for bed bugs. The experimental chemical
      lure mixture increased Climbup insect interceptor catch by 2.2 times. Results
      exhibit a distinct positive relationship between the CO2 release rates and bed
      bug trap catches. There were no significant differences between CO2 derived from
      cylinders and CO2 generated from sugar and yeast mixture in their attractiveness
      to bed bugs. The findings suggest an effective and affordable monitor can be made
      incorporating the new pitfall trap design, a sugar and yeast mixture, and a
      chemical lure.

PMID- 24020297
TI  - Lufenuron suppresses the resistance of Formosan subterranean termites (Isoptera:
      Rhinotermitidae) to entomopathogenic bacteria.
AB  - Pesticides can negatively affect insect immunity. Although studies show that
      Formosan subterranean termites, Coptotermes formosanus Shiraki, are resistant to
      microbial infections, the effects of pesticides on disease resistance is not well
      studied. In this study, C. formosanus previously fed lufenuron was exposed to
      each of the three entomopathogenic bacteria, Pseudomonas aeruginosa (Schroeter)
      Migula, Serratia marcescens Bizio, and Bacillus thuringiensis Berliner subsp.
      israelensis. We found that termite mortality was significantly higher and
      synergistic in the combination of lufenuron and P. aeruginosa compared with
      treatment of lufenuron or P. aeruginosa alone. Other bacteria and lufenuron
      combinations were not quite as effective. Interestingly, only in treatments
      without lufenuron did termites show carcass-burying behavior. The results
      indicate that lufenuron, a chitin synthesis inhibitor, can suppress Formosan
      subterranean termite resistance to P. aeruginosa. Possible suppression mechanisms
      are discussed.

PMID- 24020298
TI  - Baseline susceptibility to Cry1Ac insecticidal protein in Heliothis virescens
      (Lepidoptera: Noctuidae) populations in Brazil.
AB  - The tobacco budworm, Heliothis virescens (F.), is one of the target pests of
      genetically modified cotton expressing Cry1Ac insecticidal protein (Bt cotton)
      derived from Bacillus thuringiensis Berliner. This study was conducted to
      evaluate the susceptibility of field-collected populations of H. virescens to
      Cry1Ac to establish a baseline for use in an insect resistance management program
      for Bt cotton in Brazil. Insects were sampled from the main Brazilian cotton
      growing regions (Bahia, Mato Grosso, Mato Grosso do Sul, and Goias) during the
      cropping seasons of 2007/08 and 2008/09. Cry1Ac susceptibility was estimated by
      using diet incorporation bioassays. H. virescens was highly susceptible to Cry1Ac
      protein. The estimated LC50 values varied from 0.18 to 0.66 microg of Cry1Ac/ml
      of diet among the 2007-2008 populations (approximately 3.7-fold variation).
      Similarly, the EC50 values based on growth inhibition ranged from 0.0053 to
      0.0161 microg of Cry1Ac/ml of diet for the 2007-2008 populations (approximately
      3.0-fold variation). A joint analysis of the mortality data across all tested
      populations was used to develop and validate the diagnostic concentrations of 3.1
      and 5.6 microg of Cry1Ac/ml of diet, the upper bound of the confidence interval
      and twice the LC99 were selected, for resistance monitoring programs of H.
      virescens to Cry1Ac protein in Brazil.

PMID- 24020299
TI  - Lethal and sublethal effects of spinosad on Spodoptera exigua (Lepidoptera:
      Noctuidae).
AB  - As a selective biological insecticide, spinosad has been used widely for the
      control of pests including beet armyworm, Spodoptera exigua (Hubner)
      (Lepidoptera: Noctuidae). To form effective pest control strategies, lethal and
      sublethal effects should be considered for a complete analysis of spinosad
      impact. However, few studies have been reported to investigate sublethal effects
      of spinosad on S. exigua. This study attempts to evaluate the lethal and
      sublethal effects of spinosad on this pest by recording and analyzing various
      toxicological and physiological parameters. The toxicity of spinosad against S.
      exigua was determined under laboratory conditions by oral exposure of late second
      instar larvae to the compound. The LC50 values of spinosad to S. exigua at 48 and
      72 h after treatment were 0.317 and 0.293 mg x kg(-1), respectively. Spinosad at
      sublethal concentrations significantly extended the developmental period of
      survivor larvae, and reduced larval wet weight. Postexposure effects were
      indicated by decreased pupation ratio and pupal weight, by prolonged prepupal and
      pupal periods and by decreased emergence ratio, fecundity and longevity of
      adults. The net replacement rate (Ro) tended to be lower in the exposed spinosad
      groups than those in the unexposed spinosad group. Intrinsic rate of population
      increase (r(m)) for the high-dose group (0.365) was significantly lower than the
      control (0.521) and the low-dose group (0.521), but the latter two were not
      significantly difference. These results suggest that the combination of lethal
      and sublethal effects of spinosad might affect S. exigua population dynamics
      significantly by decreasing its survival and reproduction, and by delaying its
      development.

PMID- 24020300
TI  - Regression analysis of dynamics of insecticide resistance in field populations of
      Chilo suppressalis (Lepidoptera: Crambidae) during 2002-2011 in China.
AB  - To understand the evolution of insecticide resistance in the Asiatic rice borer,
      Chilo suppressalis (Walker) (Lepidoptera: Crambidae), in field, regression
      analysis based on a linear or nonlinear model was adopted for analyzing
      resistance dynamics to six insecticides of two field populations of the
      Lianyungang (LYG) and Ruian (RA) populations during 2002-2011. For the low-level
      resistance population, LYG population, sustained susceptibilities to abamectin
      and fipronil were seen for 10 yr; a polynomial curve regression model showed an
      increase in resistance to chlorpyrifos; exponential growth models fit to the
      resistance dynamics to triazophos and deltamethrin, and a sigmoidal growth curve
      for monosultap. For the high-level multiple resistance population, RA population,
      a slight increase from susceptible to a minor resistance to abamectin could be
      modeled by a polynomial cubic equation; an exponential growth model fit to the
      increase of resistance to fipronil from 8.7-fold to 33.6-fold; a sine waveform
      model fit to the vibrating tendency of resistance to chlorpyrifos; the dynamics
      of resistance to triazophos could be modeled by two combined curves, with a
      polynomial growth model and a sine waveform model; the high level of resistance
      to monosultap could be modeled with a sine waveform model; and a significant
      linear growth relationship of the resistance to deltamethrin of the RA population
      over years was found. Then, the relationship between dynamics of resistance
      development to insecticides among the field populations of C. suppressalis and
      the application history of pesticides for controlling rice borers was discussed.

PMID- 24020301
TI  - Dramatic changes in the genotypic frequencies of target insecticide resistance in
      French populations of Myzus persicae (Hemiptera: Aphididae) over the last decade.
AB  - In 2001, although target site resistance against pyrethroids was wide-spread in
      clonal populations of Myzus persicae on oilseed rape in France (kdr), target site
      resistance against carbamates was rare. Starting in 2005, control failure by
      carbamates appeared. The current study was designed to document changes in
      insecticide-resistant genotype frequencies in France during the last decade. Two
      resistant genotypes (RGs) were dominant in populations in 2009-2010: RG1 with the
      kdr 1014F allele (16%), RG2 with the MACE 431F allele and the atypical s-kdr 918L
      allele (83%). The widespread prevalence of RG2 suggests that a substantial shift
      has occurred (allele 431F in < 2% individuals in 2001) presumably in response to
      agrichemicals. Analysis of neutral markers revealed that 2009-2010 populations
      were composed of two differentiated genetic pools (instead of one in 2001) and
      that RG2 was found in two divergent superclones of M. persicae. Possible
      explanations for these observed shifts in population structure and especially for
      the dramatic increase of the double mutant RG2 are discussed.

PMID- 24020302
TI  - Acaricide resistance in Tetranychus urticae (Acari: Tetranychidae) populations
      from Cyprus.
AB  - Five field and greenhouse populations of the twospotted spider mite, Tetranychus
      urticae Koch (Acari: Tetranychidae), were collected from five different districts
      across the island of Cyprus, both in field and greenhouse crops, and tested to
      determine levels of resistance. Standard leaf-disk spray application bioassay
      procedures were used to determine the LC50s for five chemicals: abamectin,
      acrinathrin, fenazaquin, pirimiphos methyl, and bifenazate. Selection of these
      compounds was based on the widespread use by farmers as well as on the frequent
      control failures against T. urticae reported in the past. Resistance of T.
      urticae was detected to abamectin, acrinathrin, fenazaquin, and pirimiphos
      methyl. The resistance ratios were calculated relative to the German susceptible
      reference strain. The highest resistance ratios at LC50 value were recorded for
      abamectin in a greenhouse rose population (RR = 3822), followed by a field bean
      (RR = 1356) and field tomato population (RR = 1320). Significantly high
      resistance levels were also found for acrinathrin where the highest resistance
      ratios at LC50 were recorded in a field bean T. urticae population (RR = 903).
      For fenazaquin, the highest resistance levels were recorded in a field tomato
      population (RR = 310). Lower resistance levels were found for pirimiphos methyl
      (13.3 < RR < 77.4) in all populations. Low susceptibility of T. urticae was
      observed for bifenazate (2.7 < RR < 24.4) in all populations. These results
      suggest that at least the use of abamectin and acrinathrin should be avoided or
      minimized for the control of T. urticae populations in indoor and outdoor
      environments.

PMID- 24020303
TI  - Insecticide resistance status of field populations of Spodoptera exigua
      (Lepidoptera: Noctuidae) from China.
AB  - Beet armyworm, Spodoptera exigua (Hubner), is a serious pest of vegetables in
      China, and its control is heavily dependent on chemical insecticides. The current
      resistance status of nine insecticides was investigated in 16 field populations
      collected from seven provinces of China during 2009-2012. Compared with the
      susceptible strain WH-S, some field populations evolved various levels of
      resistance to eight of the nine insecticides tested: emamectin benzoate (4- to
      348-fold), indoxacarb (2- to 41-fold), spinosad (5- to 38-fold),
      chlorantraniliprole (2- to 44-fold), tebufenozide (2- to 87-fold), chlorfluazuron
      (3- to 31-fold), cypermethrin (79- to 1240-fold), and chlorpyrifos (8- to 3,080
      fold), but no significant resistance was detected to chlorfenapyr (0.4- to 7
      fold). This indicates that chlorfenapyr has no cross-resistance with these other
      currently used insecticides. Four consecutive years' resistance screening at two
      places shows that resistance patterns were different between populations from
      Luhe (Jiangsu Province) and Fengxian (Shanghai), which are approximately 300 km
      apart. Resistance levels to chlorpyrifos were much higher in populations from
      Luhe (877- to 3,080-fold) than from Fengxian (8- to 110-fold). Fengxian
      populations developed moderate levels of resistance to tebufenozide (13- to 87
      fold), but no resistance in Luhe populations (2- to 6-fold). However, Luhe
      populations developed moderate levels of resistance to chlorfluazuron (21- to 31
      fold), but there was no resistance in Fengxian populations (3- to 5-fold). It is
      suggested that local insecticide selection determined resistance patterns
      although S. exigua has long-distance migratory potential. Adaptive resistance
      management tactics (such as rotations) should be designed and implemented based
      on the resistance patterns of S. exigua for each geographic area.

PMID- 24020305
TI  - Characterization of resistance to adult spittlebugs (Hemiptera: Cercopidae) in
      Brachiaria spp.
AB  - Nymphs and adults of several spittlebug (Hemiptera: Cercopidae) species are key
      pests of forage brachiariagrasses (Brachiaria spp.) in tropical America. To
      support current breeding programs, a series of experiments aimed at
      characterizing the mechanisms of resistance to adult feeding damage were carried
      out. Five genotypes were used: two susceptible checks (CIAT 0606 and CIAT 0654)
      and three nymph-resistant genotypes (CIAT 36087, CIAT 6294, and SX01NO/0102).
      Test insects were Aeneolamia varia (F.), A. reducta (Lallemand), and Zulia
      carbonaria (Lallemand). The nymph-resistant genotypes showed tolerance to all
      spittlebug species tested. Tolerance in these genotypes can be classified as only
      moderate given the extent of losses (60-80%) caused by both female and male
      adults. None of the nymph-resistant genotypes had antibiotic effects on adults
      feeding on foliage. The results also indicated that antixenosis for feeding is
      not a plausible explanation for lower damage scores and less biomass losses in
      resistant genotypes. The fact that adult longevity (usually 8 d) was not affected
      when the adults were forced to feed on roots of a genotype with strong antibiotic
      resistance to nymphs is regarded as additional evidence that resistances to
      nymphs and to adults in Brachiaria are largely independent.

PMID- 24020304
TI  - Differentially expressed genes of Coptotermes formosanus (Isoptera:
      Rhinotermitidae) challenged by chemical insecticides.
AB  - Coptotermes formosanus Shiraki (Isoptera: Rhinotermitidae) termites are harmful
      social insects to wood constructions. The current control methods heavily depend
      on the chemical insecticides with increasing resistance. Analysis of the
      differentially expressed genes mediated by chemical insecticides will contribute
      to the understanding of the termite resistance to chemicals and to the
      establishment of alternative control measures. In the present article, a full
      length cDNA library was constructed from the termites induced by a mixture of
      commonly used insecticides (0.01% sulfluramid and 0.01% triflumuron) for 24 h, by
      using the RNA ligase-mediated Rapid Amplification cDNA End method. Fifty-eight
      differentially expressed clones were obtained by polymerase chain reaction and
      confirmed by dot-blot hybridization. Forty-six known sequences were obtained,
      which clustered into 33 unique sequences grouped in 6 contigs and 27 singlets.
      Sixty-seven percent (22) of the sequences had counterpart genes from other
      organisms, whereas 33% (11) were undescribed. A Gene Ontology analysis classified
      33 unique sequences into different functional categories. In general, most of the
      differential expression genes were involved in binding and catalytic activity.

PMID- 24020306
TI  - Influence of the corn resistance gene Mv on the fitness of Peregrinus maidis
      (Hemiptera: Delphacidae) and on the transmission of maize mosaic virus
      (Rhabdoviridae: Nucleorhabdovirus).
AB  - Crops that are resistant to pests and pathogens are cost-effective for the
      management of pests and diseases. A corn (Zea mays L.) breeding program conducted
      in Hawaii has identified a source of heritable resistance to maize mosaic virus
      (MMV) (Rhabdoviridae: Nucleorhabdovirus). This resistance is controlled by the
      gene Mv, which has been shown to have a codominant action. To date, no studies
      have examined whether the resistance associated with this gene affects only MMV
      or whether it also affects the insect vector, the corn planthopper Peregrinus
      maidis (Ashmead) (Hemiptera: Delphacidae). Here, we examined the life history of
      the corn planthopper and its ability to transmit MMV on near isogenic lines that
      were homozygous dominant (Mv/Mv), homozygous recessive (mv/mv), or heterozygous
      (Mv/mv) for the gene. A field trial was also conducted to study the colonization
      of the corn plants with different genotypes by the planthopper. Although field
      observations revealed slightly lower densities ofplanthoppers on corn with the
      genotype Mv/Mv than on the inbreds with the genotype mv/mv and their hybrids with
      the genotype Mv/mv, laboratory assays showed no effects of the gene on
      planthopper development, longevity, or fecundity. In the field, the corn lines
      Mv/Mv had a lower incidence of MMV-infected plants. However, in the greenhouse,
      the transmission of MMV to corn seedlings did not differ across the near isogenic
      lines, although the corn lines Mv/Mv showed a delayed onset of symptoms compared
      with the corn lines mv/mv and Mv/mv. The acquisition of MMV by corn planthoppers
      on the corn genotypes Mv/Mv and Mv/mv averaged 0.2, whereas the acquisition on
      the corn genotypes mv/mv averaged > 0.3. Our results show that the Mv gene does
      not influence the fitness of the planthopper vector, suggesting that it may
      confer resistance by other means, possibly by limiting virus replication or
      movement within the host plant.

PMID- 24020307
TI  - Effects of two Bt rice lines T2A-1 and T1C-19 on the ecological fitness and
      detoxification enzymes of Nilaparvata lugens (Hemiptera: Delphacidae) from
      different populations.
AB  - The brown planthopper, Nilaparvata lugens Stal (Hemiptera: Delphacidae), exhibits
      geographic and temporal variations in its virulence and damage characteristics on
      cultivated rice varieties, so the potential ecological risk of the nontarget
      effectiveness of Bt rice on different brown planthopper populations should be
      addressed. The nontarget effects of two Bt rice lines T2A-1 (Cry2A rice) and T1C
      19 (Cry1C rice) on six brown planthopper populations with geographical, virulent,
      and resistant variations were evaluated. Populations differed significantly in
      relation to brown planthopper nymphal survival, nymphal duration, and female
      adult weight. T2A-1 and T1C-19 did not affect the ecological fitness parameters
      of brown planthopper compared with the parental non-Bt rice MH63. Both esterase
      and glutathione-S-transferase activities differed between brown planthopper
      populations. Esterase activity of some brown planthopper populations was
      significantly affected by the rice lines. It is important to take account of
      these findings in management ofnontarget brown planthopper in Cry2A or Cry1C rice
      in the future.

PMID- 24020308
TI  - The resistance and correlation analysis to three species of cereal aphids
      (Hemiptera: Aphididae) on 10 wheat varieties or lines.
AB  - Winter wheat resistance is an efficient and environmentally friendly means to
      controlling aphids. By using principal component analysis and correlation
      analysis, we evaluated the resistance of 10 winter wheat varieties or lines from
      three countries to the following three aphid species: Sitobion avenae,
      Rhopalosiphum padi, and Schizaphis graminum. The data show that Batis was
      susceptible to Si. avenae and R. padi, but had adverse effect on the development
      of Sc. graminum; Astron was advantageous to WG and r(m) of Si. avenae and R.
      padi, but not to Sc. graminum; Amigo was resistant to Sc. graminum and R. padi,
      but susceptible to Si. avenae; 98-10-35 was resistant to Si. avenae and R. padi,
      but not to Sc. graminum; 98-10-30 was adverse to growth and fecundity of Si.
      avenae, but better for Sc. graminum and R. padi; Xiaoyan22 was susceptible to Sc.
      graminum, but not to R. padi; Ww2730 were resistant to Si. avenae, but
      susceptible to Sc. graminum; 186tm was susceptible to R. padi, but caused high
      mortality for Si. avenae and Sc. graminum. Correlation analysis suggests the
      wheat varieties or lines that were resistant to Si. avenae were always resistant
      to R. padi, but susceptible to Sc. graminum. However, the overall similarities in
      resistance classifications were not because of the same phenotypic characters of
      the wheat varieties or lines. We conclude that the wheat varieties or lines had
      specific different resistances to the three aphid species, and the resistant
      traits (antibiosis) can be defined at two or more hierarchical levels. There was
      even a stronger "trade-off" for the comparison of Si. avenae versus Sc. graminum
      and R. padi versus Sc. graminum.

PMID- 24020309
TI  - Insecticidal efficacy of silica gel with Juniperus oxycedrus ssp. oxycedrus
      (Pinales: Cupressaceae) essential oil against Sitophilus oryzae (Coleoptera:
      Curculionidae) and Tribolium confusum (Coleoptera: Tenebrionidae).
AB  - Laboratory bioassays were carried out to evaluate the effect of silica gel
      enhanced with the essential oil (EO) of Juniperus oxycedrus L. ssp. oxycedrus
      (Pinales: Cupressaceae) (derived from berry specimens from Greece) against adults
      of Sitophilus oryzae (L.) (Coleoptera: Curculionidae) and Tribolium confusum
      Jacquelin du Val (Coleoptera: Tenebrionidae). For that purpose, a dry mixture
      consisting of 500 mg of silica gel that had absorbed 2.18 mg of EO (total weight:
      502.18 mg) was tested at three doses; 0.125, 0.250, and 0.5 g/kg of wheat,
      corresponding to 125, 250, and 500 ppm, respectively, and silica gel alone at 0.5
      g/kg of wheat corresponding to 500 ppm, at different exposure intervals (24 and
      48 h and 7 and 14 d for S. oryzae; 24 and 48 h and 7, 14, and 21 d for T.
      confusum). The chemical content of the specific EO was determined by gas
      chromatography (GC)-mass spectrometry (MS) analyses indicating the presence of 31
      constituents with myrcene and germacrene-D being the predominant compounds. The
      bioactivity results for S. oryzae indicated that 48 h of exposure in wheat
      resulted in an 82% mortality for treatment with 500 ppm of the enhanced silica
      gel. For 7 d of exposure, 100 and 98% of S. oryzae adults died when they were
      treated with 500 and 250 ppm of enhanced silica gel, respectively. At 14 d of
      exposure, all adults died both at 250 and 500 ppm of enhanced silica gel. At 48
      h, 7 and 14 d of exposure significantly less S. oryzae adults died in wheat
      treated with silica gel alone than at 250 or 500 ppm of enhanced silica gel. In
      the case of T. confusum, at 7 d of exposure, mortality in wheat treated with
      silica gel only was significantly higher in comparison to the other treatments.
      At the 14 d of exposure mortality in wheat treated with 500 ppm of silica gel
      alone was significantly higher than 125 and 250 ppm of the enhanced silica gel.
      Similar trends were also noted at 21 d of exposure, indicating that there is no
      enhancement effect from the addition of the EO. Results herein suggest that the
      simultaneous use of silica gel and J. oxycedrus ssp. oxycedrus EO enhances
      significantly its activity against S. oryzae.

PMID- 24020310
TI  - Variation in susceptibility of field strains of three stored grain insect species
      to spinosad and chlorpyrifos-methyl plus deltamethrin on hard red winter wheat.
AB  - Spinosad and chlorpyrifos-methyl plus deltamethrin efficacy at labeled rates on
      hard red winter wheat were evaluated against 11 field strains of the red flour
      beetle, Tribolium castaneum (Herbst); six strains of the sawtoothed grain beetle,
      Oryzaephilus surinamensis (L.); and two strains of the lesser grain borer,
      Rhyzopertha dominica (F.), collected mostly from farm-stored grain in Kansas.
      Adults were exposed to wheat treated with spinosad at 1 mg (active ingredient)/kg
      or chlorpyrifos-methyl plus deltamethrin at three plus 0.5 mg (active
      ingredient)/kg. Adult mortality was assessed after 7 and 14 d and progeny
      production after 42 d. Spinosad did not provide complete mortality or progeny
      suppression of T. castaneum and O. surinamensis field strains, but was effective
      against R. dominica strains. Chlorpyrifos-methyl plus deltamethrin produced
      complete mortality and progeny suppression of field strains all three species.
      The two least susceptible T. castaneum and O. surinamensis strains and the two R.
      dominica strains were chosen for dose-response tests only with spinosad. The LD99
      values for T. castaneum and R. dominica field strains were similar to that of the
      corresponding laboratory strains. Corresponding values for the two O.
      sturinamensis field strains were significantly greater (approximately 6 times)
      than the laboratory strain. The effective dose for progeny reduction (ED99) of
      only one R. dominica field strain was significantly greater (approximately 2
      times) than the laboratory strain. The baseline susceptibility data of field
      strains of three insect species to spinosad will be useful for monitoring
      resistance development when this product is commercially released as a grain
      protectant.

PMID- 24020311
TI  - Efficacy and application considerations of selected residual acaricides against
      the mold mite Tyrophagus putrescentiae (Acari: Acaridae) in simulated retail
      habitats.
AB  - The mold mite, Tyrophagus putrescentiae (Schrank), is a stored product pest of
      economic significance that commonly infests many types of food and animal feed
      products. There is limited information regarding pest management tactics,
      including residual acaricides for managing this pest in retail store habitats.
      The purpose of this study was to assess the potential of commercially available
      acaricides that could provide a protective barrier near susceptible food packages
      destined for consumer use. Mite mortality at 24 and 48 h was measured after
      exposing mites to acaricide residues applied to a nonporous surface. Two
      additional factors included in the study were humidity and the presence of an
      adjuvant to facilitate spread of acaricide on nonporous surfaces. Increasing
      humidity levels generally decreased acaricide efficacy. Use of the adjuvant
      itself did not appear to affect efficacy, but the type of application (wet or
      slurry, or dry) of dust acaricides significantly affected efficacy. The potential
      for residual acaricides to act as a barrier (within 24-48 h) against dispersal of
      this mite was discussed.

PMID- 24020312
TI  - An artificial diet for rearing Cochliomyia macellaria (Diptera: Calliphoridae).
AB  - Larvae of the secondary screwworm, Cochliomyia macellaria (F.), feed on carrion
      and may sometimes cause animal myiasis. They have been reared in the laboratory
      on various animal tissues to study their growth and development because of their
      importance in forensic science. We use secondary screwworms in our laboratory for
      preliminary experiments as a model for the primary screwworm, Cochliomyia
      hominivorax (Coquerel), which has been eradicated from the United States. C.
      macellaria larvae reared on animal tissues produced a putrid odor, an unfavorable
      condition in the laboratory, and variable pupal size and weight, bringing into
      question the validity of use as a model for C. hominivorax. Therefore, studies
      were conducted to develop a less odiferous artificial diet with reduced
      variability in resulting pupae by comparing three diets: 1) an artificial diet
      prepared from spray-dried blood, spray-dried poultry egg, dry milk substitute,
      and solidified with a polyacrylate polymer gel; 2) a fresh blood-based diet
      prepared similarly, except fresh bovine blood was used in place of spray-dried
      blood; and 3) a beef liver diet. Data from seven life-history parameters of
      resulting insects were collected and analyzed. Larval and pupal weights of C.
      macellaria reared on both the dry and fresh blood-based diets were significantly
      higher than those reared on the liver diet. Numbers of pupae and percentage of
      adult emergence were also significantly higher from both dry blood and fresh
      blood-based diets than those reared on the liver diet. Female flies developing
      from larvae reared on dry and fresh blood-based diets laid significantly more
      eggs than females developing from larvae reared on the liver diet. Results show
      that C. macellaria larvae developed and grew normally in the dry and fresh blood
      based diets, indicating that an artificial diet can effectively replace the liver
      diet commonly used for rearing C. macellaria.

PMID- 24020313
TI  - Host status and fruit odor response of Drosophila suzukii (Diptera:
      Drosophilidae) to figs and mulberries.
AB  - Drosophila suzukii Matsumura (Diptera: Drosophilidae) is an agricultural pest
      with a wide host range. It is known to infest fruit that are still ripening on
      the plant, as well as rotting and damaged fruit. Our study sought to determine
      whether D. suzukii use mulberries (Morus spp.) and figs (Ficus carica (L.)) as
      hosts, as their host status was ambiguous. Accordingly, we collected 25 field
      infested fruit and counted the numbers of D. suzukii emerging from them. We also
      sought to determine whether female D. suzukii would respond to olfactory cues
      from ripe figs and mulberries. As the host population has been known to impact
      host odor response, flies from mulberry, fig, and cherry origins were tested in
      "one-choice" olfactometry studies. Our results show that mulberries and figs can
      serve as hosts for D. suzukii and that female flies will respond to their odors.
      The host population did affect response to fruit odors, although further studies
      are necessary to determine habitat fidelity. This has implications for management
      of this pest, especially in backyard and mixed fruit orchard situations, which
      commonly occur in the current range of D. suzukii, and fig and mulberry may serve
      as a pest reservoir for other hosts and cultivated crops.

PMID- 24020314
TI  - Hospitals and terrorism: the realities; the future; mitigating risks.
AB  - Terrorist acts near hospitals and actual attacks on hospitals have become
      frequent in other countries and should not be ignored by security planners in
      this country, the author warns. In this article he sets forth steps which can be
      taken now to deal with and prevent such occurrences here.

PMID- 24020315
TI  - Armed violent intruders: requiring a prescription for protection.
AB  - In this article, the authors present a detailed plan for hospitals of all sizes
      and police to work more effectively together to better protect staff and patients
      during an armed intruder incident.

PMID- 24020316
TI  - The insider threat--a new aspect of biosecurity.
AB  - The need for those responsible for security at hospital research centers to take
      steps to counter insider threats to use biomedical and microbiological research
      and for perverted purposes is real, says the author. He spells out what the
      threats consist of suspicious behaviors to be aware of and reporting procedures
      for effective resolution that will enable life science researchers and law
      enforcement to successfully work together to thwart such threats.

PMID- 24020317
TI  - Why healthcare facilities are vulnerable to crime.
AB  - Although the public's view of healthcare facilities is that they are inherently
      safe and secure, administrators and staff members in hospitals are very aware
      that they could be vulnerable to an episode of violence at any time, according to
      the author. Today, crimes, including homicide, are an ever-present reality in
      healthcare facilities, they report, citing recent studies which attempt to
      explain why this is so. The article is based on the introduction to the IAHSS and
      IHSS Foundation 2012 Crime and Security Trends Survey. The complete survey is
      accessible to members in the Reference Section of the IAHSS web page.

PMID- 24020318
TI  - Planning high security/high profile events.
AB  - The author who has lead in the planning and implementation of some of the most
      notorious trials and events, both in Canada and internationally, describes how
      such these experiences could be applied to focused high security planning in the
      health care industry.

PMID- 24020319
TI  - Redesigning and retrofitting existing facilities for behavioral healthcare.
AB  - With many states closing or consolidating in-patient behavioral healthcare units,
      more and more patients are being treated in emergency departments, and in
      hospital settings. At the same time, design and treatment standards have changed
      from wards and shared rooms to single-room care. This article addresses how a
      facilities design, smart and considerate choices, and flexibility can make a
      safer and more calming environment, not only for dedicated behavioral health
      patients, but for staff as well.

PMID- 24020320
TI  - Keeping off-site employees safe.
AB  - To help a hospital's home healthcare nurses better protect themselves against
      violence, the authors developed a training program that gave employees
      information on what to look for, what to do in an emergency and provided them
      with other policies and procedures to follow. In the article, they describe the
      use of role playing exercises and scenario-based instruction that allowed better
      retention on examinations, and also influenced the employees' attitude toward
      training positively.

PMID- 24020321
TI  - Background checks: coming up short.
AB  - In this article, the author spells out the flaws and omissions in the way
      background checks are conducted, especially by hospitals. He provides pointers on
      avoiding these flaws and their potential costs.

PMID- 24020322
TI  - More than conventional wisdom--the better way to make and justify security
      choices.
AB  - In this article, the author provides the garage manager with a risk assessment
      tool that can give him a more justifiable way to determine the kind and extent of
      security he should provide.

PMID- 24020323
TI  - Project management; considerations for success.
AB  - During the past two years the author was a project leader for three Information
      Communication Technology (ICT) security related systems projects for a newly
      built healthcare facility. These projects were: a CCTV system, an Access Control
      system and an Identity & Access Management system. During those two years he
      gained experiences on how to coop with ICT projects related to security and
      healthcare as well as some pitfalls to be contended with along the way. With this
      article, he shares his experiences so that colleagues can benefit from them when
      they are a project leaders for their health facility and need to better decide
      how or how not to address their project and project issues.

PMID- 24020324
TI  - Patience with difficult patients.
AB  - The author, an advocate of an approach to healthcare security solutions that
      emphasizes compassion and safety in the sensitive healthcare environment,
      describes how a strike team of security, behavioral health and ED staff was able
      to collaboratively defuse situations with combative patients without resorting to
      forceful hands-on action.

PMID- 24020325
TI  - Four ways your security team can impact HCAHPS scores.
AB  - All hospitals are now required to conduct Hospital Consumer Assessment of
      Healthcare Providers and Systems (HCAHPS) surveys by CMS and to publish their
      results. The author points out that Security is affected by HCAHPS scores and can
      also affect them. In the article he spells out the ways Security can have a
      positive influence on survey results.

PMID- 24020326
TI  - IAHSS-a history of our association.
AB  - This article has been prepared for the Journal as a permanent record of the
      beginnings and development of IAHSS, with the assistance of two of its charter
      members as well as current staffmembers.

PMID- 24020327
TI  - Eldercare--the coming storm.
AB  - The author maintains that Long Term Care sites, specifically nursing homes, are
      the most vulnerable of healthcare facilities to natural and manmade disasters,
      and that casualties among the elderly in recent hurricanes and tornados have been
      greatly underestimated.

PMID- 24020328
TI  - Conducting a hazardous vulnerability assessment for a long term care facility.
AB  - The article and outline of an all hazards emergency management plan which follows
      are excerpted from the "IAHSS Long Term Care Safety and Security Guide," prepared
      by the IAHSS Long Term Security Task Force. The complete guide is available to
      members in the Educational Materials section of the IAHSS web page.

PMID- 24020329
TI  - Mobile's impact on hospital IT security in 2013: how your institution can adapt
      to BYOD.
AB  - Just as ID theft of patient information has become largely a low-tech problem
      frequently involving the participation of physical security, so does the latest
      threat to protecting privacy, BYOD. In the article, the author spells out the
      problems and proposes solutions.

PMID- 24020330
TI  - Second hyperpolarizability of C-H, C-D, and C=N stretch vibrations determined
      from computational Raman activities and a comparison with experiments.
AB  - We have recently demonstrated that the second hyperpolarizability gamma of a
      selected vibrational mode of a molecule can be determined by using the
      computational Raman activity against an internal standard with a known Raman
      gamma value. This approach provides a convenient way for prediction of the gamma
      magnitude of DOVE four wave mixing spectroscopy, an optical analogue to two
      dimensional (2D) NMR. Here, by using the Hartree-Fock (HF) method, the density
      functional theory (DFT) method, and the second-order Moller-Plesset perturbation
      theory (MP2) method, we extend our early work from the less anharmonic region
      <2000 cm(-1) into the more anharmonic region >2000 cm(-1) covering C-H, C-D, and
      C=N stretching modes of benzene, deuterated benzene, acetonitrile, deuterated
      acetonitrile, and tetrahydrofuran. The computed Raman gamma values of these
      vibrational modes have been determined by using either the 992 cm(-1) Raman band
      of benzene or the compound's own Raman band (C-C stretch) around 800-1000 cm(-1)
      as an internal standard. In this more anharmonic region, the HF method with a
      larger basis set provides the best outputs and the predicted Raman gamma values
      agree well with experimental values for most of the vibrational modes studied. By
      choosing a suitable method and basis set, this facile approach could be applied
      to a broader spectral range for Raman gamma estimation of various materials. 

PMID- 24020331
TI  - AutoDensity: an automated method to measure mammographic breast density that
      predicts breast cancer risk and screening outcomes.
AB  - INTRODUCTION: While Cumulus - a semi-automated method for measuring breast
      density - is utilised extensively in research, it is labour-intensive and
      unsuitable for screening programmes that require an efficient and valid measure
      on which to base screening recommendations. We develop an automated method to
      measure breast density (AutoDensity) and compare it to Cumulus in terms of
      association with breast cancer risk and breast cancer screening outcomes.
      METHODS: AutoDensity automatically identifies the breast area in the mammogram
      and classifies breast density in a similar way to Cumulus, through a fast, stand
      alone Windows or Linux program. Our sample comprised 985 women with screen
      detected cancers, 367 women with interval cancers and 4,975 controls (women who
      did not have cancer), sampled from first and subsequent screening rounds of a
      film mammography screening programme. To test the validity of AutoDensity, we
      compared the effect estimates using AutoDensity with those using Cumulus from
      logistic regression models that tested the association between breast density and
      breast cancer risk, risk of small and large screen-detected cancers and interval
      cancers, and screening programme sensitivity (the proportion of cancers that are
      screen-detected). As a secondary analysis, we report on correlation between
      AutoDensity and Cumulus measures. RESULTS: AutoDensity performed similarly to
      Cumulus in all associations tested. For example, using AutoDensity, the odds
      ratios for women in the highest decile of breast density compared to women in the
      lowest quintile for invasive breast cancer, interval cancers, large and small
      screen-detected cancers were 3.2 (95% CI 2.5 to 4.1), 4.7 (95% CI 3.0 to 7.4),
      6.4 (95% CI 3.7 to 11.1) and 2.2 (95% CI 1.6 to 3.0) respectively. For Cumulus
      the corresponding odds ratios were: 2.4 (95% CI 1.9 to 3.1), 4.1 (95% CI 2.6 to
      6.3), 6.6 (95% CI 3.7 to 11.7) and 1.3 (95% CI 0.9 to 1.8). Correlation between
      Cumulus and AutoDensity measures was 0.63 (P < 0.001). CONCLUSIONS: Based on the
      similarity of the effect estimates for AutoDensity and Cumulus inmodels of breast
      density and breast cancer risk and screening outcomes, we conclude that
      AutoDensity is a valid automated method for measuring breast density from
      digitised film mammograms.

PMID- 24020332
TI  - Universal coverage with insecticide-treated nets - applying the revised
      indicators for ownership and use to the Nigeria 2010 malaria indicator survey
      data.
AB  - BACKGROUND: Until recently only two indicators were used to evaluate malaria
      prevention with insecticide-treated nets (ITN): "proportion of households with
      any ITN" and "proportion of the population using an ITN last night". This study
      explores the potential of the expanded set of indicators recommended by the Roll
      Back Malaria Monitoring and Evaluation Reference Group (MERG) for comprehensive
      analysis of universal coverage with ITN by applying them to the Nigeria 2010
      Malaria Indicator Survey data. METHODS: The two additional indicators of
      "proportion of households with at least one ITN for every two people" and
      "proportion of population with access to an ITN within the household" were
      calculated as recommended by MERG. Based on the estimates for each of the four
      ITN indicators three gaps were calculated: i) households with no ITN, ii)
      households with any but not enough ITN, iii) population with access to ITN not
      using it. In addition, coverage with at least one ITN at community level was
      explored by applying Lot Quality Assurance Sampling (LQAS) decision rules to the
      cluster level of the data. All outcomes were analysed by household background
      characteristics and whether an ITN campaign had recently been done. RESULTS:
      While the proportion of households with any ITN was only 42% overall, it was 75%
      in areas with a recent mass campaign and in these areas 66% of communities had
      coverage of 80% or better. However, the campaigns left a considerable intra
      household ownership gap with 66% of households with any ITN not having enough for
      every family member. In contrast, the analysis comparing actual against potential
      use showed that ITN utilization was good overall with only 19% of people with
      access not using the ITN, but with a significant difference between the North,
      where use was excellent (use gap 11%), and the South (use gap 36%) indicating the
      need for enhanced behaviour change communication. CONCLUSIONS: The expanded ITN
      indicators to assess universal coverage provide strong tools for a comprehensive
      system effectiveness analysis that produces clear, actionable evidence of
      progress as well as the need for specific additional interventions clearly
      differentiating between gaps in ownership and use.

PMID- 24020333
TI  - Rh(III)-catalyzed C-H activation and double directing group strategy for the
      regioselective synthesis of naphthyridinones.
AB  - A general Rh(III)-catalyzed synthesis of naphthyridinone derivatives is
      described. It relies on a double-activation and directing approach leveraging
      nicotinamide N-oxides as substrates. In general, high yields and selectivities
      can be achieved using low catalyst loadings and mild conditions (room
      temperature) in the couplings with alkynes, while alkenes require slightly more
      elevated temperatures. 

PMID- 24020334
TI  - Negatively charged nitrogen-vacancy centers in a 5 nm thin 12C diamond film.
AB  - We report successful introduction of negatively charged nitrogen-vacancy (NV(-))
      centers in a 5 nm thin, isotopically enriched ([(12)C] = 99.99%) diamond layer by
      CVD. The present method allows for the formation of NV(-) in such a thin layer
      even when the surface is terminated by hydrogen atoms. NV(-) centers are found to
      have spin coherence times of between T2 ~ 10-100 MUs at room temperature.
      Changing the surface termination to oxygen or fluorine leads to a slight increase
      in the NV(-) density, but not to any significant change in T2. The minimum
      detectable magnetic field estimated by this T2 is 3 nT after 100 s of averaging,
      which would be sufficient for the detection of nuclear magnetic fields exerted by
      a single proton. We demonstrate the suitability for nanoscale NMR by measuring
      the fluctuating field from ~10(4) proton nuclei placed on top of the 5 nm diamond
      film.

PMID- 24020336
TI  - Microbial ecology of biogeochemical interfaces - diversity, structure, and
      function of microhabitats in soil.

PMID- 24020335
TI  - Addition of SNAP to perinatal risk factors improves the prediction of
      bronchopulmonary dysplasia or death in critically ill preterm infants.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common serious pulmonary
      morbidity in premature infants. The score for neonatal acute physiology (SNAP) is
      a physiologic severity index for neonatal intensive care and correlates well with
      neonatal mortality and clinical outcomes. The prognostic value of the SNAP score
      for BPD in preterm infants remains to be clarified. The aim of the study was to
      determine whether SNAP can predict the development of BPD or death, and to
      investigate the contribution of SNAP to the predictive accuracy of other
      potential perinatal risk factors for the adverse outcome in critically ill
      preterm infants. METHODS: We conducted a study in 160 critically ill preterm
      infants with less than 33 gestational weeks. The original SNAP score was
      prospectively calculated based on 28 items collected during the first 24 hours of
      admission. The potential perinatal risk factors were assessed during the first 72
      hours of life. Major outcome measures were BPD and mortality before the time of
      BPD screening. RESULTS: Of the 160 infants, 17 died and 41 developed BPD. The
      SNAP score was significantly associated with BPD or death (odds ratio [OR] =1.28;
      95% confidence interval [CI], 1.16-1.41; p <0.001), even after adjustment for
      gestational age (OR =1.27; 95% CI, 1.13-1.41; p <0.001). High SNAP score was an
      independent predictor of BPD or death (area under the curve [AUC] =0.78; 95% CI,
      0.70-0.85; p <0.001), with additional predictive value when combined with other
      perinatal risk factors. Multivariate regression analysis resulted in a final
      model, including SNAP, gestational age, apnea of prematurity, patent ductus
      arteriosus, and surfactant use as independent risk factors, with a higher
      predictive accuracy compared with individual components (AUC =0.92; 95% CI, 0.87
      0.96; p <0.001). CONCLUSIONS: SNAP is associated with adverse outcome of BPD or
      death. High SNAP scores are predictive of BPD or death in critically ill preterm
      infants, and add prognostic value to other perinatal risk factors.

PMID- 24020337
TI  - Still casting its long shadow: rheumatic heart disease in Australia and New
      Zealand.

PMID- 24020338
TI  - Should law have a role in end-of-life care?

PMID- 24020339
TI  - Systematic review of the prevalence of gout and hyperuricaemia in Australia.
AB  - AIMS: Gout is a growing health problem worldwide especially in affluent
      countries, such as Australia. Gout and hyperuricaemia are associated with the
      metabolic syndrome, diabetes mellitus, obesity and hypertension. More
      importantly, Australia has a growing prevalence of these important health
      problems. The aim of this study was to systematically review published
      information regarding the prevalence of gout and hyperuricaemia in Australia.
      METHODS: A systematic search was undertaken of the MEDLINE, EMBASE and Web of
      Science databases, as well as relevant websites for journal articles and reports
      relating to the prevalence of hyperuricaemia and gout in Australia. RESULTS:
      Twenty-five journal articles and five reports were included in the review. Data
      collected in a standardised way show gout increased in prevalence from 0.5%
      population prevalence to 1.7% population prevalence from 1968 to 1995/1996. There
      has been a significant rise in the prevalence of gout in the Australian
      Aboriginal population from 0% in 1965 to 9.7% in men and 2.9% in women in 2002.
      Consistent with the rise in gout prevalence, serum uric acid in blood donors has
      increased from 1959 to 1980 (17% in 30- to 40-year-old men). CONCLUSIONS: The
      rate of gout and hyperuricaemia in Australia is high in relation to comparable
      countries and is increasing. The prevalence of gout in elderly male Australians
      is second only to New Zealand, which has the highest reported rate in the world.
      Further research on Aboriginal and Torres Strait Islander gout and hyperuricaemia
      is required as a result of the lack of contemporary data.

PMID- 24020340
TI  - Dying at 23 with 1p36 deletion syndrome: Laura's family story.
AB  - Laura was unusual. She had always been different and at times difficult. She was
      born with a genetic disorder, diagnosed as 1p36 deletion syndrome when she was 21
      years old. At 23 she suffered her first cardiac arrest at home and entered the
      hospital system for the first time apart from infancy. After initially appearing
      to do well, she suffered a second cardiac arrest 10 weeks after admission. This
      was followed by an irreversible deterioration and she died 14 weeks after
      admission. We her family had been with her throughout her traumatic experience.
      This is our story. 

PMID- 24020341
TI  - Referral to specialist palliative care.
AB  - Recent literature has suggested that earlier referral to palliative care can
      improve quality of life and prognosis. The decision to refer to palliative care
      is a complex process that can involve an interplay of interpersonal, subjective
      and institutional factors. Negotiating this referral process can be challenging
      to a medical specialist from a professional and personal viewpoint. What remains
      unknown is what actually influences the individual clinician to refer a patient
      to palliative care. 

PMID- 24020342
TI  - Secondary amyloidosis in Indigenous Australians.
AB  - Secondary amyloidosis (AA) is an established consequence of many chronic
      inflammatory conditions. In the developed world, it is most often the result of
      rheumatological disease. However, the relative frequency of underlying causes may
      be different in indigenous populations. We present a case series of three remote
      living, Indigenous Australians found to have pathologically confirmed amyloidosis
      and renal impairment at diagnosis. The presence of an underlying inflammatory
      condition was unclear in two cases. The remaining case had established
      bronchiectasis and suffered rapidly progressive renal impairment at a young age. 

PMID- 24020343
TI  - Prognostic factors in the elderly: a profile and outcomes study of a community
      palliative care service.
AB  - Our ageing population creates challenges for palliative care, including accuracy
      of prognostication. This study highlights this by profiling the outcomes of an
      Australian, community-based palliative service over 6 months with collection of
      epidemiological, comorbidity and physical function data. Most patients had
      cancer, comorbidities and died during the study. Low scores on the Australian
      modified Karnofsky Performance Scale and the presence of congestive cardiac
      failure were predictive of shorter survival. 

PMID- 24020344
TI  - How can we improve junior doctor prescribing?
AB  - The large number of medications available has complicated the learning of drug
      therapy for medical students at a time when pharmacology training has been
      substantially reduced. Attempts to remedy this include: improving the pharmaco
      therapeutics curriculum; interactive web-based learning and students developing a
      personal formulary. The approach adopted by the University of Wollongong Medical
      School is to integrate clinical pharmacology throughout the course, with the
      Student Preferred-drugs Formulary linking pharmacology and common diseases.
      Evidence from other countries suggests this should enhance prescribing by medical
      graduates. 

PMID- 24020346
TI  - Mesiotemporal changes on magnetic resonance imaging in neurosyphilis.
AB  - We report a case of neurosyphilis with magnetic resonance imaging (MRI) brain
      scan findings compatible with a diagnosis of herpes simplex encephalitis with
      negative testing for herpes simplex virus in the cerebral spinal fluid. An
      extensive review of the literature has been undertaken revealing 24 cases
      worldwide where there are mesiotemporal changes on MRI concurrent with a
      diagnosis of neurosyphilis. Therefore, it is now well established that
      neurosyphilis, 'the great imitator', should be considered in the differential
      diagnosis in all patients demonstrating mesiotemporal changes on MRI, changes
      usually seen in herpes simplex encephalitis. 

PMID- 24020345
TI  - Palliative care for patients with chronic obstructive pulmonary disease:
      exploring the landscape.
AB  - Patients with chronic obstructive pulmonary disease experience a substantial
      symptom burden, high levels of psychosocial need and significant mortality. This
      epidemiological study reveals that the majority of patients are cared for in the
      public hospital system (64%) and generally die in hospital (72%) with a number of
      identifiable predictors of 6-month mortality. Our results suggest that palliative
      care services need to be redirected from a community-based admission focus to a
      model that is responsive to emergency and acute care hospital systems. 

PMID- 24020347
TI  - Pancytopenia due to severe folate deficiency.

PMID- 24020348
TI  - Nontyphoidal Salmonella prosthetic valve endocarditis.

PMID- 24020349
TI  - Our experience with anti-neutrophil cytoplasmic antibody-associated systemic
      vasculitis.

PMID- 24020350
TI  - Anti-neutrophil cytoplasmic antibody-associated systemic vasculitis: nature or
      nurture?

PMID- 24020351
TI  - Variation in avian brain shape: relationship with size and orbital shape.
AB  - There is wide variation in brain shape among birds. Differences in brain
      dimensions reflect species-specific sensory capacities and behavioral repertoires
      that are shaped by environmental and biological factors during evolution. Most
      previous studies aimed at defining factors impacting brain shape have used
      volumetric or linear measurements. However, few have explored the quantitative
      indices of three-dimensional (3D) brain geometry that are absolutely imperative
      to understanding avian evolutionary history. This study aimed: (i) to explore the
      relationship between brain shape and overall brain size; and (ii) to assess the
      relationship between brain shape and orbital shape. Avian brain endocasts were
      reconstructed from computed tomography images and analyzed using 3D geometric
      morphometrics. Principal component analysis revealed dominant regional variations
      in avian brain shape and shape correlations between the telencephalon and
      cerebellum, between the cerebellum and myelencephalon, and between the
      diencephalon and optic tectum. Brain shape changes relative to total brain size
      were determined by multivariate regression analysis. Larger brain size was
      associated with a relatively slender telencephalon and differences in brain
      orientation. The correlation between brain shape and orbital shape was assessed
      by two-block partial least-squares analysis. Relatively round brains with a
      ventrally flexed brain base were associated with rounder orbits, while narrower
      brains with a flat brain base were associated with more elongated orbits. The
      shapes of functionally associated avian brain regions are correlated, and orbital
      size and shape are dominant factors influencing the overall shape of the avian
      brain. 

PMID- 24020352
TI  - Volumetric analysis of the subthalamic and red nuclei based on magnetic resonance
      imaging in patients with Parkinson's disease.
AB  - Parkinson's disease (PD) is associated with degeneration of the dopaminergic
      neurons in the substantia nigra. The subthalamic nucleus (STN) plays a pivotal
      role in the pathogenesis. However, there is not much known about the
      morphological changes in the STN. The red nucleus (RN) has many connections with
      the motor coordinating pathways although it is not primarily involved in the
      pathogenesis. In this study we aimed to compare the volumes of the STN and RN
      measured by magnetic resonance imaging in PD patients and controls to investigate
      how these structures are affected at the morphological level. Twenty patients
      with PD and twenty age/sex matched controls were enrolled in this study. Severity
      score was determined by Hoehn & Yahr staging: 6 at stage II and 14 at stage III
      in med-off state. Imaging was performed by a 1.5 Tesla (T) MR scanner.
      Measurements of total brain and normalized STN and RN volumes were performed by
      manual planimetry using Image J software. No statistically significant
      differences were observed between two groups based on age or gender and disease
      stage and nuclei volumes. The total estimated brain volumes were not different
      between PD patients and controls. However, normalized volumes of the STN and RN
      were 14% and 16% larger, respectively, in PD patients compared to the controls (p
      < 0.05). Our findings suggest that the volumes of the STN and RN are increased in
      patients with PD. These changes possibly reflect the altered metabolic activity
      of these regions demonstrated by neurophysiological studies. 

PMID- 24020353
TI  - Intakes of total and individual flavonoids by US adults.
AB  - Knowing the dietary flavonoid intake of individuals and populations is the first
      step to clearly understand their health effects. Dietary flavonoid intake studies
      have been hampered by the lack of flavonoid food composition data. The objectives
      of this study were to estimate intakes of individual, classes and total
      flavonoids in the US adults; to evaluate the effects of socio-demographic factors
      on the flavonoid consumption patterns; and to establish major dietary sources of
      flavonoids. We calculated flavonoid intakes using the most updated USDA flavonoid
      and isoflavone databases, and the National Health and Nutrition Examination
      Survey (NHANES) III 24-h dietary recall (DR). Estimated mean total flavonoid
      intake by US adults was 344.83 +/- 9.13 mg/day. The flavan-3-ols (191.99 +/- 6.84
      mg/day) were the most abundant flavonoid class. The three most dominant
      individual flavonoids were catechin, epicatechin and polymers. Tea, wine, beer,
      citrus fruits and apples were the most important sources of total flavonoid
      intakes in the US adults.

PMID- 24020354
TI  - How much H(2)O(2) is produced by recombinant D-amino acid oxidase in mammalian
      cells?
AB  - Yeast D-amino acid oxidase (DAO) can serve as a genetically encoded producer of
      reactive oxygen species (ROS) in redox signaling studies. However, dynamics of
      hydrogen peroxide production and its sensitivity to externally added D-alanine (D
      Ala) in cells have not been determined. Here we show that DAO, fused to a
      genetically encoded H2O2 indicator HyPer, can be used for controlled production
      of ROS in living eukaryotic cells. We found a clear heterogeneity in ROS
      production dynamics between individual cells. Moreover, different cell lines
      demonstrated distinct sensitivity to added D-Ala. Finally, by comparing signals
      generated by the HyPer-DAO fusion protein versus coexpressed HyPer and DAO
      proteins, we show that the fusion system is more sensitive to hydrogen peroxide
      production. Our results show the utility of the HyPer-DAO genetically encoded
      system for redox signaling studies and suggest that H2O2 produced by DAO in the
      cytoplasm acts locally in close proximity to the enzyme.

PMID- 24020355
TI  - The predicted secretome and transmembranome of the poultry red mite Dermanyssus
      gallinae.
AB  - BACKGROUND: The worldwide distributed hematophagous poultry red mite Dermanyssus
      gallinae (De Geer, 1778) is one of the most important pests of poultry. Even
      though 35 acaricide compounds are available, control of D. gallinae remains
      difficult due to acaricide resistances as well as food safety regulations. The
      current study was carried out to identify putative excretory/secretory (pES)
      proteins of D. gallinae since these proteins play an important role in the host
      parasite interaction and therefore represent potential targets for the
      development of novel intervention strategies. Additionally, putative
      transmembrane proteins (pTM) of D. gallinae were analyzed as representatives of
      this protein group also serve as promising targets for new control strategies.
      METHODS: D. gallinae pES and pTM protein prediction was based on putative protein
      sequences of whole transcriptome data which was parsed to different
      bioinformatical servers (SignalP, SecretomeP, TMHMM and TargetP). Subsequently,
      pES and pTM protein sequences were functionally annotated by different
      computational tools. RESULTS: Computational analysis of the D. gallinae proteins
      identified 3,091 pES (5.6%) and 7,361 pTM proteins (13.4%). A significant
      proportion of pES proteins are considered to be involved in blood feeding and
      digestion such as salivary proteins, proteases, lipases and carbohydrases. The
      cysteine proteases cathepsin D and L as well as legumain, enzymes that cleave
      hemoglobin during blood digestion of the near related ticks, represented 6 of the
      top-30 BLASTP matches of the poultry red mite's secretome. Identified pTM
      proteins may be involved in many important biological processes including cell
      signaling, transport of membrane-impermeable molecules and cell recognition.
      Ninjurin-like proteins, whose functions in mites are still unknown, represent the
      most frequently occurring pTM. CONCLUSION: The current study is the first
      providing a mite's secretome as well as transmembranome and provides valuable
      insights into D. gallinae pES and pTM proteins operating in different metabolic
      pathways. Identifying a variety of molecules putatively involved in blood feeding
      may significantly contribute to the development of new therapeutic targets or
      vaccines against this poultry pest.

PMID- 24020357
TI  - C-H activation of 2,4,6-triphenylphosphinine: synthesis and characterization of
      the first homoleptic phosphinine-iridium(III) complex fac-[Ir(C^P)3].
AB  - Access to homoleptic phosphinine-based coordination compounds of d(6) metals has
      so far remained elusive. We report here on the preparation and full
      characterization of the first homoleptic phosphinine-iridium(III) complex,
      obtained by C-H activation of 2,4,6-triphenylphosphinine with [Ir(acac)3]. This
      result opens up new perspectives for the implementation of such aromatic
      heterocycles in more applied research fields. 

PMID- 24020356
TI  - Kinetic mechanism of DNA polymerization catalyzed by human DNA polymerase
      epsilon.
AB  - Eukaryotes require highly accurate and processive DNA polymerases to ensure
      faithful and efficient replication of their genomes. DNA polymerase epsilon
      (Polepsilon) has been shown to catalyze leading-strand DNA synthesis during
      replication in vivo, but little is known about the kinetic mechanism of
      polymerization catalyzed by this replicative enzyme. To elucidate this mechanism,
      we have generated a truncated, exonuclease-deficient mutant of the catalytic
      subunit of human Polepsilon (Polepsilon exo-) and carried out pre-steady-state
      kinetic analysis of this enzyme. Our results show that Polepsilon exo-, as other
      DNA polymerases, follows an induced-fit mechanism when catalyzing correct
      nucleotide incorporation. Polepsilon exo- binds DNA with a Kd(DNA) of 79 nM and
      dissociates from the E.DNA binary complex with a rate constant of 0.021 s(-1).
      Although Polepsilon exo- binds a correct incoming nucleotide weakly with a
      Kd(dTTP) of 31 MUM, it catalyzes correct nucleotide incorporation at a fast rate
      constant of 248 s(-1) at 20  degrees C. Both a large reaction amplitude
      difference (42%) between pulse-chase and pulse-quench assays and a small
      elemental effect (0.9) for correct dTTP incorporation suggest that a slow
      conformational change preceding the chemistry step limits the rate of correct
      nucleotide incorporation. In addition, our kinetic analysis shows that Polepsilon
      exo- exhibits low processivity during polymerization. To catalyze leading-strand
      synthesis in vivo, Polepsilon likely interacts with its three smaller subunits
      and additional replication factors in order to assemble a replication complex and
      significantly enhance its polymerization processivity. 

PMID- 24020358
TI  - Effect of dimethyl sulfoxide on inhibition of post-ovariectomy osteopenia in
      rats.
AB  - There is increasing evidence that oxidative stress, due to estrogen deficiency,
      leads to osteopenia. In this study, dimethyl sulfoxide (DMSO), an antioxidant
      solvent, was used against post-ovariectomy osteopenia (PO) in rats. Forty female
      rats were divided into 5 groups randomly as follows: Sham, control group; OVX,
      ovariectomized group; DMSO1, ovariectomized injected DMSO (0.5 ml/kg/d ip);
      DMSO2, ovariectomized injected DMSO (1 ml/kg/day ip) and DMSO3, ovariectomized
      injected DMSO (2 ml/kg/d ip). DMSO therapy started 1 week after ovariectomy and
      continued for 13 weeks. After 13th weeks, sera were prepared, and then L4
      vertebrae and right tibial bones rinsed in fixative. Serum bone alkaline
      phosphatase (BALP), osteocalcin, pyridinoline, malondialdehyde (MDA) and
      glutathione (GSH) were measured. Trabecular volume density, trabecular and cortex
      thickness were estimated. Osteoclast and osteoblast numbers were counted
      morphometrically. The data were analyzed by ANOVA and then post hoc Tukey test at
      p < 0.05. The increase of pyridinoline and decrease of BALP in DMSO injected
      groups were inhibited compared with OVX group (p < 0.05). In DMSO injected
      groups, decrease of bone density, trabecular volume density, thickness of
      trabecular and tibial cortex were inhibited compared with OVX group (p < 0.05).
      MDA decreased significantly in DMSO injected groups compared with OVX group.
      Osteoclast number decreased in DMSO injected groups compared with OVX group (p <
      0.05). Osteoblast number did not show significant change in DMSO groups compared
      with OVX group. In conclusion, DMSO ameliorates PO through decrease of osteoclast
      number, osteoclast inhibition and osteoblast activation. These effects may
      probably be mediated via antioxidant property of DMSO.

PMID- 24020363
TI  - Metabolic adaptations of Leishmania donovani in relation to differentiation, drug
      resistance, and drug pressure.
AB  - Antimonial (sodium stibogluconate, SSG) resistance and differentiation have been
      shown to be closely linked in Leishmania donovani, with SSG-resistant strains
      showing an increased capacity to generate infectious (metacyclic) forms. This is
      the first untargeted LC-MS metabolomics study which integrated both phenomena in
      one experimental design and provided insights into metabolic differences between
      three clinical L. donovani strains with a similar genetic background but
      different SSG-susceptibilities. We performed this analysis at different stages
      during promastigote growth and in the absence or presence of drug pressure. When
      comparing SSG-resistant and SSG-sensitive strains, a number of metabolic changes
      appeared to be constitutively present in all growth stages, pointing towards a
      clear link with SSG-resistance, whereas most metabolic changes were only detected
      in the stationary stage. These changes reflect the close intertwinement between
      SSG-resistance and an increased metacyclogenesis in resistant parasites. The
      metabolic changes suggest that SSG-resistant parasites have (i) an increased
      capacity for protection against oxidative stress; (ii) a higher fluidity of the
      plasma membrane; and (iii) a metabolic survival kit to better endure infection.
      These changes were even more pronounced in a resistant strain kept under Sb(III)
      drug pressure. 

PMID- 24020364
TI  - Perioperative evaluation of tumescent anaesthesia technique in bitches submitted
      to unilateral mastectomy.
AB  - BACKGROUND: Tumescent anaesthesia (TA) is a widely used technique in oncologic
      surgeries necessitating large resection margins. This technique produces
      transoperative and postoperative analgesia, reduces surgical bleeding, and
      facilitates tissue divulsion. This prospective, randomised, blind study evaluated
      the use of TA in bitches submitted to mastectomy and compared the effect of TA
      with an intravenous fentanyl bolus. A 2.5-mcg/kg intravenous fentanyl bolus (n =
      10) was compared with TA using 0.275% lidocaine (n = 10) in bitches submitted to
      unilateral mastectomy. Sedation was performed by intramuscular (IM) injection of
      0.05 mg/kg of acepromazine combined with 2 mg/kg of meperidine. Anaesthesia was
      induced with 5 mg/kg of intravenous propofol and maintained with isoflurane/O2.
      Heart and respiratory rates; systolic, mean, and diastolic arterial blood
      pressures; central venous pressure; SpO2; ETCO2; inspired and expired isoflurane
      concentrations; and temperature were measured transoperatively. Visual analogue
      scales for sedation and pain and the Glasgow composite and Melbourne pain scales
      were used for postoperative assessment. The surgeon investigated the quality of
      the surgical approach, considering bleeding and resection ability, and the
      incidence of postoperative wound complications. RESULTS: The heart rate was lower
      and the end-tidal isoflurane concentration was higher in dogs treated with
      fentanyl than in dogs treated with TA. A fentanyl bolus was administered to 8 of
      10 dogs treated with fentanyl and to none treated with TA. Intraoperative
      bleeding and the mammary gland excision time were lower in dogs treated with TA.
      The maximal mean and individual plasma lidocaine concentrations were 1426 +/- 502
      ng/ml and 2443 ng/ml at 90 minutes after infiltration, respectively. The Glasgow
      Composite Pain Scale scores were higher in dogs treated with fentanyl than in
      dogs treated with TA until 2 hours after extubation. CONCLUSIONS: Compared with
      intravenous fentanyl, TA in bitches: may be easily performed in non-inflamed,
      ulcerated, adhered mammary tumours; has an isoflurane-sparing effect; improves
      transoperative and immediate postoperative analgesia; is apparently safe for use
      in clinical conditions as evidenced by the fact that it did not produce any
      adverse signs or lidocaine plasma concentrations compatible with toxicity; does
      not modify the recovery time; and facilitates the surgical procedure without
      interfering with wound healing.

PMID- 24020365
TI  - Gall volatiles defend aphids against a browsing mammal.
AB  - BACKGROUND: Plants have evolved an astonishing array of survival strategies. To
      defend against insects, for example, damaged plants emit volatile organic
      compounds that attract the herbivore's natural enemies. So far, plant volatile
      responses have been studied extensively in conjunction with leaf chewing and sap
      sucking insects, yet little is known about the relationship between plant
      volatiles and gall-inducers, the most sophisticated herbivores. Here we describe
      a new role for volatiles as gall-insects were found to benefit from this plant
      defence. RESULTS: Chemical analyses of galls triggered by the gregarious aphid
      Slavum wertheimae on wild pistachio trees showed that these structures contained
      and emitted considerably higher quantities of plant terpenes than neighbouring
      leaves and fruits. Behavioural assays using goats as a generalist herbivore
      confirmed that the accumulated terpenes acted as olfactory signals and feeding
      deterrents, thus enabling the gall-inducers to escape from inadvertent predation
      by mammals. CONCLUSIONS: Increased emission of plant volatiles in response to
      insect activity is commonly looked upon as a "cry for help" by the plant to
      attract the insect's natural enemies. In contrast, we show that such volatiles
      can serve as a first line of insect defences that extends the 'extended
      phenotype' represented by galls, beyond physical boundaries. Our data support the
      Enemy hypothesis insofar that high levels of gall secondary metabolites confer
      protection against natural enemies.

PMID- 24020366
TI  - Spheroid culture for enhanced differentiation of human embryonic stem cells to
      hepatocyte-like cells.
AB  - Stem cell-derived hepatocyte-like cells hold great potential for the treatment of
      liver disease and for drug toxicity screening. The success of these applications
      hinges on the generation of differentiated cells with high liver specific
      activities. Many protocols have been developed to guide human embryonic stem
      cells (hESCs) to differentiate to the hepatic lineage. Here we report cultivation
      of hESCs as three-dimensional aggregates that enhances their differentiation to
      hepatocyte-like cells. Differentiation was first carried out in monolayer culture
      for 20 days. Subsequently cells were allowed to self-aggregate into spheroids.
      Significantly higher expression of liver-specific transcripts and proteins,
      including Albumin, phosphoenolpyruvate carboxykinase, and asialoglycoprotein
      receptor 1 was observed. The differentiated phenotype was sustained for more than
      2 weeks in the three-dimensional spheroid culture system, significantly longer
      than in monolayer culture. Cells in spheroids exhibit morphological and
      ultrastructural characteristics of primary hepatocytes by scanning and
      transmission electron microscopy in addition to mature functions, such as biliary
      excretion of metabolic products and cytochrome P450 activities. This three
      dimensional spheroid culture system may be appropriate for generating high
      quality, functional hepatocyte-like cells from ESCs. 

PMID- 24020370
TI  - Assisted injection among people who inject drugs in Thailand.
AB  - BACKGROUND: Assisted injection is common among people who inject drugs (IDU), and
      has been associated with elevated risk for HIV infection and overdose. However,
      this practice has not been explored in the Asian context, including in Thailand,
      where HIV prevalence among IDU remains high. METHODS: Using multivariate logistic
      regression, we examined the prevalence and correlates of assisted injecting among
      IDU participating in the Mitsampan Community Research Project in Bangkok. We also
      sought to identify reasons for engaging in assisted injecting and those who
      provide this form of assistance. RESULTS: In total, 430 IDU participated in this
      study, including 376 (87.5%) who reported having ever required assistance
      injecting, and 81 (18.8%) who reported assisted injecting in the previous six
      months. In multivariate analyses, assisted injecting in the previous six months
      was independently and positively associated with being female (adjusted odds
      ratio [AOR] = 2.42; 95% confidence interval [CI]: 1.40 - 4.18), being a weekly
      heroin injector (AOR = 1.78; 95% CI: 0.99 - 3.20), syringe sharing (AOR = 2.08;
      95% CI: 1.18 - 3.68) and soft-tissue infection (AOR = 3.51; 95% CI: 1.43 - 2.53).
      Having a longer injecting career (AOR = 0.96; 95% CI: 0.94 - 0.99) was negatively
      associated with assisted injecting. Primary reasons given for engaging in
      assisted injecting included being new to injecting and lacking knowledge on how
      to inject. The most common providers of assistance with injecting were close
      friends. CONCLUSION: We found a high prevalence of assisted injecting among IDU
      in Bangkok, with females, frequent heroin injectors, those with shorter injecting
      careers being more likely to engage in this practice. Those who require help with
      the injecting process are more likely to share syringes, and have skin
      infections. These findings indicate the need for interventions focused on
      promoting safer and self-administered injections.

PMID- 24020369
TI  - Pain management policies and practices in pediatric emergency care: a nationwide
      survey of Italian hospitals.
AB  - BACKGROUND: Pain experienced by children in emergency departments (EDs) is often
      poorly assessed and treated. Although local protocols and strategies are
      important to ensure appropriate staff behaviours, few studies have focussed on
      pain management policies at hospital or department level. This study aimed at
      describing the policies and reported practices of pain assessment and treatment
      in a national sample of Italian pediatric EDs, and identifying the assocoated
      structural and organisational factors. METHODS: A structured questionnaire was
      mailed to all the 14 Italian pediatric and maternal and child hospitals and to 5
      general hospitals with separate pediatric emergency room. There were no refusals.
      Information collected included the frequency and mode of pain assessment,
      presence of written pain management protocols, use of local anaesthetic (EMLA
      cream) before venipuncture, and role of parents. General data on the hospital and
      ED were also recorded. Multiple Correspondence Analysis was used to explore the
      multivariable associations between the characteristics of hospitals and EDs and
      their pain management policies and practices. RESULTS: Routine pain assessment
      both at triage and in the emergency room was carried out only by 26% of surveyed
      EDs. About one third did not use algometric scales, and almost half (47.4%) did
      not have local protocols for pain treatment. Only 3 routinely reassessed pain
      after treatment, and only 2 used EMLA. All EDs allowed parents' presence and most
      (17, 89.9%) allowed them to stay when painful procedures were carried out. Eleven
      hospitals (57.9%) allowed parents to hold their child during blood sampling.
      Pediatric and maternal and child hospitals, those located in the North of Italy,
      equipped with medico-surgical-traumatological ED and short stay observation, and
      providing full assessment triage over 24 hours were more likely to report
      appropriate policies for pain management both at triage and in ER. A nurses to
      admissions ratio >= median was associated with better pain management at triage.
      CONCLUSIONS: Despite availability of national and international guidelines,
      pediatric pain management is still sub-optimal in Italian emergency departments.
      Multifaceted strategies including development of local policies, staff
      educational programs, and parental involvement in pain assessment should be
      carried out and periodically reinforced.

PMID- 24020371
TI  - Expansion of ruminant-specific microRNAs shapes target gene expression divergence
      between ruminant and non-ruminant species.
AB  - BACKGROUND: Understanding how species-specific microRNAs (miRNAs) contribute to
      species-specific phenotypes is a central topic in biology. This study aimed to
      elucidate the role of ruminant-specific miRNAs in shaping mRNA expression
      divergence between ruminant and non-ruminant species. RESULTS: We analyzed miRNA
      and mRNA transcriptomes generated by Illumina sequencing from whole blood samples
      of cattle and a closely related non-ruminant species, pig. We found evidence of
      expansion of cattle-specific miRNAs by analyzing miRNA conservation among 57
      vertebrate species. The emergence of cattle-specific miRNAs was accompanied by
      accelerated sequence evolution at their target sites. Further, the target genes
      of cattle-specific miRNAs show markedly reduced expression compared to their pig
      and human orthologues. We found that target genes with conserved or non-conserved
      target sites of cattle-specific miRNAs exhibit reduced expression. One of the
      significantly enriched KEGG pathway terms for the target genes of the cattle
      specific miRNAs is the insulin signalling pathway, raising the possibility that
      some of these miRNAs may modulate insulin resistance in ruminants. CONCLUSIONS:
      We provide evidence of rapid miRNA-mediated regulatory evolution in the ruminant
      lineage. Cattle-specific miRNAs play an important role in shaping gene expression
      divergence between ruminant and non-ruminant species, by influencing the
      expression of targets genes through both conserved and cattle-specific target
      sites.

PMID- 24020372
TI  - Critical illness induces nutrient-independent adipogenesis and accumulation of
      alternatively activated tissue macrophages.
AB  - INTRODUCTION: We previously reported that in artificially-fed critically ill
      patients, adipose tissue reveals an increase in small adipocytes and accumulation
      of M2-macrophages. We hypothesized that nutrient-independent factors of critical
      illness explain these findings, and that the M2-macrophage accumulation may not
      be limited to adipose tissue. METHODS: In a long-term cecal ligation and puncture
      (CLP) mouse model of sepsis, we compared the effect of parenteral nutrition (CLP
      fed, n = 13) with nutrient restriction (CLP-restricted, n = 11) on body
      composition, adipocyte size and macrophage accumulation in adipose tissue, liver
      and lungs. Fed healthy mice (n = 11) were studied as controls. In a human study,
      in vivo adipose tissue biopsies were studied from ICU patients (n = 40) enrolled
      in a randomized control trial which compared early initiation of parenteral
      nutrition (PN) versus tolerating nutrient restriction during the first week of
      ICU stay. Adipose tissue morphology was compared with healthy human controls (n =
      13). RESULTS: Irrespective of nutritional intake, critically ill mice lost
      weight, fat and fat-free mass. Adipocyte number, proliferation marker
      Proliferating Cell Nuclear Antigen (PCNA) and adipogenic markers PPARgamma and
      CCAAT/enhancer binding protein-beta (C/EBPbeta) increased with illness,
      irrespective of nutritional intake. M2-macrophage accumulation was observed in
      adipose tissue, liver and lungs of critically ill mice. Macrophage M2-markers
      correlated with CCL2 expression. In adipose tissue biopsies of critically ill
      patients, increased adipogenic markers and M2 macrophage accumulation were
      present irrespective of nutritional intake. CONCLUSIONS: Adipogenesis and
      accumulation of tissue M2-macrophages are hallmarks of prolonged critical
      illness, irrespective of nutritional management. During critical illness, M2
      macrophages accumulate not only in adipose tissue, but also in the liver and
      lungs.

PMID- 24020373
TI  - Endoplasmic reticulum-associated ubiquitin-conjugating enzyme Ube2j1 is a novel
      substrate of MK2 (MAPKAP kinase-2) involved in MK2-mediated TNFalpha production.
AB  - The p38 MAPK (mitogen-activated protein kinase)/MK2 [MAPKAP (MAPK-activated
      protein) kinase-2] signalling pathway is a major regulator of stress- and
      cytokine-induced gene expression at the transcriptional and post-transcriptional
      level. Using phosphoproteomics we identified the ER (endoplasmic reticulum)
      associated ubiquitin-conjugating enzyme Ube2j1 as a potential substrate of MK2.
      We demonstrate that Ube2j1 is phosphorylated in a cytokine-, cytosolic stress-
      and LPS (lipopolysaccharide)-induced manner. The cytosolic stress-induced
      phosphorylation of Ube2j1 proceeds at Ser(184), a site described previously to be
      phosphorylated in response to ER stress, which is located in a perfect MK2
      consensus motif. The cytosolic stress-induced phosphorylation of Ube2j1, but not
      its ER-stress-induced phosphorylation is sensitive to p38/MK2 inhibitors and
      abrogated in MK2/MK3-deficient cells. In a pull-down assay we demonstrate the
      interaction of MK2 with Ube2j1 in HEK (human embryonic kidney)-293T cells.
      Furthermore, MK2 is able to phosphorylate recombinant Ube2j1, but not the S184A
      mutant in an in vitro kinase assay. These findings strongly suggest that MK2
      directly phosphorylates Ube2j1 at Ser(184) upon p38-activating stress in vivo.
      However, ectopically expressed Ube2j1-S184A mutant displays ubiquitinating
      activity towards the model substrate ER-synthesized T-cell receptor-alpha similar
      to that of the wild-type protein. Interestingly, Ube2j1 is phosphorylated in
      response to LPS also in macrophages and contributes to MK2-dependent TNFalpha
      biosynthesis by a so far unknown mechanism.

PMID- 24020374
TI  - Lipid peroxidation and antioxidant enzymes activity in Plasmodium vivax malaria
      patients evolving with cholestatic jaundice.
AB  - BACKGROUND: Plasmodium vivax infection has been considered a benign and self
      limiting disease, however, recent studies highlight the association between vivax
      malaria and life-threatening manifestations. Increase in reactive oxygen species
      has already been described in vivax malaria, as a result of the increased
      metabolic rate triggered by the multiplying parasite, and large quantities of
      toxic redox-active byproducts generated. The present study aimed to study the
      oxidative stress responses in patients infected with P. vivax, who developed
      jaundice (hyperbilirubinaemia) in the course of the disease, a common clinical
      complication related to this species. METHODS: An evaluation of the lipid
      peroxidation and antioxidant enzymes profile was performed in 28 healthy
      individuals and compared with P. vivax infected patients with jaundice, i.e.,
      bilirubin < 51.3 MUmol/L (8 patients) or without jaundice (34 patients), on day 1
      (D1) and day 14 (D14) after anti-malarial therapy. RESULTS: Hyperbilirubinaemia
      was more frequent among women and patients experiencing their first malarial
      infection, and lower haemoglobin and higher lactate dehydrogenase levels were
      observed in this group. Malondialdehyde levels and activity of celuroplasmin and
      glutathione reductase were increased in the plasma from patients with P. vivax
      with jaundice compared to the control group on D1. However, the activity of
      thioredoxin reductase was decreased. The enzymes glutathione reductase,
      thioredoxin reductase, thiols and malondialdehyde also differed between jaundiced
      versus non-jaundiced patients. On D14 jaundice and parasitaemia had resolved and
      oxidative stress biomarkers were very similar to the control group. CONCLUSION:
      Cholestatic hyperbilirubinaemia in vivax malaria cannot be totally disassociated
      from malaria-related haemolysis. However, significant increase of lipid
      peroxidation markers and changes in antioxidant enzymes in patients with P. vivax
      related jaundice was observed. These results suggest oxidative processes
      contributing to malaria pathogenesis, what may be useful information for future
      anti-oxidant therapeutical interventions in these patients.

PMID- 24020381
TI  - Nucleophilicity parameters of pyridinium ylides and their use in mechanistic
      analyses.
AB  - Kinetics of the reactions of pyridinium, isoquinolinium, and quinolinium ylides
      with diarylcarbenium ions, quinone methides, and arylidene malonates (reference
      electrophiles) have been studied in dimethylsulfoxide solution by UV-vis
      spectroscopy. The second-order rate constants (log k2) were found to correlate
      linearly with the electrophilicities E of the reference electrophiles, as
      required by the linear free-energy relationship log k(20 degrees C) = sN(N + E)
      (J. Am. Chem. Soc. 2001, 123, 9500), which allowed us to derive the nucleophile
      specific parameters N and sN for these ylides. Pyridinium substitution is found
      to have a similar effect on the reactivity of carbanionic reaction centers as
      alkoxycarbonyl substitution. Agreement between the rate constants measured for
      the 1,3-dipolar cycloadditions of pyridinium, isoquinolinium, and quinolinium
      ylides with acceptor substituted dipolarophiles (arylidenemalononitrile and
      substituted chalcone) and those calculated from E, N, and sN shows that the above
      correlation can also be employed for predicting absolute rate constants of
      stepwise or highly unsymmetrical concerted cycloadditions. Deviations between
      calculated and experimental rate constants by a factor of 10(6) were demonstrated
      to indicate a change of reaction mechanism.

PMID- 24020380
TI  - Resveratrol increases cerebral glycogen synthase kinase phosphorylation as well
      as protein levels of drebrin and transthyretin in mice: an exploratory study.
AB  - Alzheimer's disease (AD) is characterized by intraneuronal beta-amyloid plaques
      and hyperphosphorylated tau, leading to neuronal cell death and progressive
      memory losses. This exploratory work investigates if dietary resveratrol,
      previously shown to have broad anti-aging effects and improve AD pathology in
      vivo, leads to neuroprotective changes in specific protein targets in the mouse
      brain. Both wild-type and APP/PS1 mice, a transgenic AD mouse model, received
      control AIN-93G diet or AIN-93G supplemented with resveratrol. Pathology
      parameters and AD risk were assessed via measurements on plaque burden, levels of
      phosphorylated glycogen synthase kinase 3-beta (GSK3-beta), tau, transthyretin
      and drebrin. Dietary resveratrol treatment did not decrease plaque burden in
      APP/PS1 mice. However, resveratrol-fed mice demonstrated increases in GSK3-beta
      phosphorylation, a 3.8-fold increase in protein levels of transthyretin, and a
      2.2-fold increase in drebrin. This study broadens our understanding of specific
      mechanisms and targets whereby resveratrol provides neuroprotection.

PMID- 24020375
TI  - Improving the management of imported schistosomiasis haematobia in China: lessons
      from a case with multiple misdiagnoses.
AB  - BACKGROUND: Human Schistosoma haematobium infection that causes urinary
      schistosomiasis occurs in Africa and the eastern Mediterranean, and China is only
      endemic for S. japonicum. In this report, we reported an imported case with S.
      haematobium infection returning from Angola to Shaanxi Province, northwestern
      China, where S. japonicum is not endemic. FINDINGS: The case was misdiagnosed as
      ureteral calculus, invasive urothelial carcinoma and eosinophilic cystitis in
      several hospitals, and was finally diagnosed by means of serological assay
      followed by microscopic examination of the urine sediment. The patient was then
      treated with praziquantel, and a satisfactory outcome was obtained. CONCLUSIONS:
      As S. haematobium is not indigenous to China, most Chinese doctors and medical
      technicians are unfamiliar with this introduced parasitic disease, therefore,
      they need to increase the awareness of its existence when they encounter persons
      who have visited or resided in endemic areas, and the techniques for detection of
      the parasite, so as to reduce the misdiagnosis. In addition, health education
      should be given to those who will go to the endemic areas to improve their
      knowledge and awareness on prevention and control of schistosomiasis haematobia,
      thereby reducing the risk of exposure to the infested freshwater.

PMID- 24020382
TI  - Medical and surgical management after spinal cord injury: vasopressor usage,
      early surgerys, and complications.
AB  - The optimal mean arterial blood pressure for maintenance of spinal cord perfusion
      is not known. Our aim was to describe vasopressor usage and examine their effects
      in patients with spinal cord injury (SCI). We undertook a retrospective cohort
      study of 131 patients with SCI who received any kind of vasopressors to maintain
      blood pressure in the neurocritical care unit of a Level 1 trauma center (2005
      2011). Vasopressor usage and complications were obtained from the medical record.
      Neurological outcomes were evaluated by the American Spinal Injury Association
      score. Dopamine was the most commonly used vasopressor (48.0%), followed by
      phenylephrine (45.0%), norepinephrine (5.0%), epinephrine (1.5%), and vasopressin
      (0.5%). Logistic regression analysis demonstrated that complications (e.g.,
      ventricular tachycardia, troponin elevation, atrial fibrillation, heart rate >130
      or <50, etc.) due to vasopressors were independently associated with the overall
      usages of dopamine (odds ratio [OR] 8.97; p<0.001) and phenylephrine (OR, 5.92;
      p=0.004), age >=60 years old (OR, 5.16; p=0.013), and complete SCI (OR, 3.23;
      p=0.028). There was no difference in neurological improvement with either
      dopamine (OR, 1.16; p=0.788) or phenylephrine (OR 0.96; p=0.940). Incomplete SCI
      (OR, 2.64; p=0.019) and surgery <24 h after SCI (OR, 4.25; p=0.025) were
      independently associated with improved outcome. In summary, vasopressors are
      associated with increased complications in SCI patients. Further prospective
      studies are required in order to determine the potential benefits and risks of
      blood pressure management in patients with SCI.

PMID- 24020383
TI  - SULT2B1: unique properties and characteristics of a hydroxysteroid
      sulfotransferase family.
AB  - The SULT2b gene family consists of a single gene capable of generating two
      functional transcripts utilizing different transcriptional start sites in the
      first exon. This results in the translation of two separate proteins, SULT2B1a
      and SULT2B1b, with different amino-terminal peptides and approximately 95%
      identical sequences. The second distinguishing feature of the SULT2B isoforms is
      the proline/serine-rich carboxy-terminal sequence. To date, presence of the
      SULT2B gene appears limited to mammals and there is also only limited
      conservation of structure or sequence of the carboxy-terminal peptide. Although
      both SULT2B1 messages are present in human tissues, to date, only the SULT2B1b
      protein has been detected in the tissues investigated. In contrast, selective
      expression of SULT2B1a has been detected in rodent brain, whereas SULT2B1b was
      expressed in skin and intestine. Characterization of the SULT2B1 isoforms has
      been limited by the inability to isolate reliably active SULT2B1b from tissues or
      cells. SULT2B1 cDNAs can be expressed in Escherichia coli and the expressed
      active enzymes show selectivity for sulfation of 3beta-hydroxysteroids. SULT2B1b
      due to the binding properties of the amino-terminal peptides also shows high
      cholesterol sulfation activity. Although human SULT2B1b displays significant
      substrate cross-reactivity with SULT2A1, the isoforms have different tissue
      expression patterns. Human SULT2B1b also shows nuclear localization in selected
      tissues that appears related to serine phosphorylation of the carboxy-terminal
      peptide. Overall, the understanding of the properties and function of the SULT2B1
      isoforms is limited and the structural variability of the unique amino- and
      carboxy-sequences suggests significant species differences that need to be
      investigated.

PMID- 24020384
TI  - Nuclear receptors in regulation of biotransformation enzymes and drug
      transporters in the placental barrier.
AB  - Over the past 20 years, the toxicological and protective roles of the placental
      barrier with respect to drug detoxification and transporter-controlled protection
      of the fetus have been intensively examined. Several cytochrome P450 enzymes are
      expressed in placental trophoblast at different stages of pregnancy, though only
      a few of these have functional activity to metabolize xenobiotics. Drug
      transporters such as P-glycoprotein/MDR1 or breast cancer resistance protein
      (BCRP) are highly expressed in the placenta, and their functional activities have
      been demonstrated in the placenta both in vitro and in vivo. In addition, several
      studies have reported on ligand-activated transcription factors and nuclear
      receptors referred to as "xenosensors" in the placenta. The xenosensors control
      transcriptional regulation of both xenobiotic-metabolizing enzymes and drug
      transporters in different organs. Their ligands include toxic compounds and
      environmental pollutants, drugs, as well as herbal, dietary or vitamin
      supplements. Nevertheless, it remains debatable whether the placental barrier
      adapts to toxic injuries coming either from maternal medication or environmental
      contamination and whether the placenta contains a mechanism to respond
      dynamically in protecting the developing fetus. In the present paper, we
      summarize current knowledge about the activity and expression of major ligand
      activated transcriptional mechanisms involved in biotransformation enzymes and
      transporters regulation in human placenta. In particular, we highlight the
      emerging roles of aryl hydrocarbon (AHR), vitamin D (VDR), glucocorticoid (GR)
      and pregnane X (PXR) receptors in that regulation. We show that the placenta
      constitute a unique metabolizing organ with significant overlap of exogenous and
      endogenous compounds metabolism controlled by nuclear receptors.

PMID- 24020385
TI  - Turning the corner: efficient energy transfer in bent plasmonic nanoparticle
      chain waveguides.
AB  - For integrating and multiplexing of subwavelength plasmonic waveguides with other
      optical and electric components, complex architectures such as junctions with
      sharp turns are necessary. However, in addition to intrinsic losses, bending
      losses severely limit plasmon propagation. In the current work, we demonstrate
      that propagation of surface plasmon polaritons around 90 degrees  turns in silver
      nanoparticle chains occurs without bending losses. Using a far-field fluorescence
      method, bleach-imaged plasmon propagation (BlIPP), which creates a permanent map
      of the plasmonic near-field through bleaching of a fluorophore coated on top of a
      plasmonic waveguide, we measured propagation lengths at 633 nm for straight and
      bent silver nanoparticle chains of 8.0 +/- 0.5 and 7.8 +/- 0.4 MUm, respectively.
      These propagation lengths were independent of the input polarization. We
      furthermore show that subradiant plasmon modes yield a longer propagation length
      compared to energy transport via excitation of super-radiant modes. 

PMID- 24020389
TI  - Remarkable effect of iridium cyclometalation on the nonlinear absorption
      properties of a quadrupolar imine ligand.
AB  - A new type of dinuclear iridium complex, based on a quadrupolar Schiff base
      ligand, is synthesized and its structure fully characterized. Its linear and
      nonlinear spectroscopic properties are investigated, evidencing a strong
      contribution of the metal-to-ligand transitions not only to the linear absorption
      but also to the two- and three-photon absorption properties. 

PMID- 24020390
TI  - A new headspace gas chromatographic method for the determination of methanol
      content in paper materials used for food and drink packaging.
AB  - This study reports on a method for determination of methanol in paper products by
      headspace gas chromatography (HS-GC). The method is based on the hydrolysis of
      the pulp or paper matrix, using a phosphoric acid solution (42.5%) as the medium
      at 120  degrees C in 5 h (excluding air contact) in order to release matrix
      entrapped methanol, which is then determined by HS-GC. Data show that, under the
      given conditions of hydrolysis, no methanol was formed from the methoxyl groups
      in the material. Reproducibility tests of the method generated a relative
      standard deviation of <3.5%, with recovery in the range of 93.4-102%. The present
      method is reliable, accurate, and suitable for use in batch testing of the
      methanol content in paper-related materials. The method can play an important
      role in addressing food safety concerns that may be raised regarding the use of
      paper materials in food and beverage packaging. 

PMID- 24020391
TI  - Interdomain interactions support interdomain communication in human Pin1.
AB  - Pin1 is an essential mitotic regulator consisting of a peptidyl-prolyl isomerase
      (PPIase) domain flexibly tethered to a smaller Trp-Trp (WW) binding domain.
      Communication between these domains is important for Pin1 in vivo activity;
      however, the atomic basis for this communication has remained elusive. Our
      previous nuclear magnetic resonance (NMR) studies of Pin1 functional dynamics
      suggested that weak interdomain contacts within Pin1 enable allosteric
      communication between the domain interface and the distal active site of the
      PPIase domain.1,2 A necessary condition for this hypothesis is that the intrinsic
      properties of the PPIase domain should be sensitive to interdomain contact. Here,
      we test this sensitivity by generating a Pin1 mutant, I28A, which weakens the
      wild-type interdomain contact while maintaining the overall folds of the two
      domains. Using NMR, we show that I28A leads to altered substrate binding affinity
      and isomerase activity. Moreover, I28A causes long-range perturbations to
      conformational flexibility in both domains, for both the apo and substrate
      complexed states of the protein. These results show that the distribution of
      conformations sampled by the PPIase domain is sensitive to interdomain contact
      and strengthen the hypothesis that such contact supports interdomain allosteric
      communication in Pin1. Other modular systems may exploit interdomain interactions
      in a similar manner. 

PMID- 24020392
TI  - Assessing the capacity for newborn resuscitation and factors associated with
      providers' knowledge and skills: a cross-sectional study in Afghanistan.
AB  - BACKGROUND: Resuscitation with bag and mask is a high-impact intervention that
      can reduce neonatal deaths in resource-poor countries. This study assessed the
      capacity to perform newborn resuscitation at facilities offering comprehensive
      emergency obstetric and newborn care (EmONC) in Afghanistan, as well as
      individual and facility characteristics associated with providers' knowledge and
      clinical skills. METHODS: Assessors interviewed 82 doctors and 142 midwives at 78
      facilities on their knowledge of newborn resuscitation and observed them perform
      the procedure on an anatomical model. Supplies, equipment, and infrastructure
      were assessed at each facility. Descriptive statistics and simple and
      multivariate regression analyses were performed using STATA 11.2 and SAS 9.1.3.
      RESULTS: Over 90% of facilities had essential equipment for newborn
      resuscitation, including a mucus extractor, bag, and mask. More than 80% of
      providers had been trained on newborn resuscitation, but midwives were more
      likely than doctors to receive such training as part of pre-service education
      (59% and 35%, respectively, p < 0.001). No significant differences were found
      between doctors and midwives on knowledge, clinical skills, or confidence in
      performing newborn resuscitation. Doctors and midwives scored 71% and 66%,
      respectively, on knowledge questions and 66% and 71% on the skills assessment;
      75% of doctors and 83% of midwives felt very confident in their ability to
      perform newborn resuscitation. Training was associated with greater knowledge (p
      < 0.001) and clinical skills (p < 0.05) in a multivariable model that adjusted
      for facility type, provider type, and years of experience offering EmONC
      services. CONCLUSIONS: Lack of equipment and training do not pose major barriers
      to newborn resuscitation in Afghanistan, but providers' knowledge and skills need
      strengthening in some areas. Midwives proved to be as capable as doctors of
      performing newborn resuscitation, which validates the major investment made in
      midwifery education. Competency-based pre-service and in-service training,
      complemented by supportive supervision, is an effective way to build providers'
      capacity to perform newborn resuscitation. This kind of training could also help
      skilled birth attendants based in the community, at private clinics, or at
      primary care facilities save the lives of newborns.

PMID- 24020393
TI  - Accurate IMRT fluence verification for prostate cancer patients using 'in-vivo'
      measured EPID images and in-room acquired kilovoltage cone-beam CT scans.
AB  - BACKGROUND: To investigate for prostate cancer patients the comparison of 'in
      vivo' measured portal dose images (PDIs) with predictions based on a kilovoltage
      cone-beam CT scan (CBCT), acquired during the same treatment fraction, as an
      alternative for pre-treatment verification. For evaluation purposes, predictions
      were also performed using the patients' planning CTs (pCT). METHODS: To get
      reliable CBCT electron densities for PDI predictions, Hounsfield units from the
      pCT were mapped onto the CBCT, while accounting for non-rigidity in patient
      anatomy in an approximate way. PDI prediction accuracy was first validated for an
      anatomical phantom, using IMRT treatment plans of ten prostate cancer patients.
      Clinical performance was studied using data acquired for 50 prostate cancer
      patients. For each patient, 4-5 CBCTs were available, resulting in a total of
      1413 evaluated images. Measured and predicted PDIs were compared using gamma
      analyses with 3% global dose difference and 3 mm distance to agreement as
      reference criteria. Moreover, the pass rate for automated PDI comparison was
      assessed. To quantify improvements in IMRT fluence verification accuracy results
      from multiple fractions were combined by generating a gamma-image with values
      halfway the minimum and median gamma values, pixel by pixel. RESULTS: For
      patients, CBCT-based PDI predictions showed a high agreement with measurements,
      with an average percentage of rejected pixels of 1.41% only. In spite of possible
      intra-fraction motion and anatomy changes, this was only slightly larger than for
      phantom measurements (0.86%). For pCT-based predictions, the agreement
      deteriorated (average percentage of rejected pixels 2.98%), due to an enhanced
      impact of anatomy variations. For predictions based on CBCT, combination of the
      first 2 fractions yielded gamma results in close agreement with pre-treatment
      analyses (average percentage of rejected pixels 0.63% versus 0.35%, percentage of
      rejected beams 0.6% versus 0%). For the pCT-based approach, only combination of
      the first 5 fractions resulted in acceptable agreement with pre-treatment
      results. CONCLUSION: In-room acquired CBCT scans can be used for high accuracy
      IMRT fluence verification based on in-vivo measured EPID images. Combination of
      gamma results for the first 2 fractions can largely compensate for small accuracy
      reductions, with respect to pre-treatment verification, related to intra-fraction
      motion and anatomy changes.

PMID- 24020394
TI  - FACE-R--a 3D database of 400 living individuals' full head CT- and face scans and
      preliminary GMM analysis for craniofacial reconstruction.
AB  - In the past, improvements in craniofacial reconstructions (CFR) methodology
      languished due to the lack of adequate 3D databases that were sufficiently large
      and appropriate for 3-dimensional shape statistics. In our study, we created the
      "FACE-R" database from CT records and 3D surface scans of 400 clinical patients
      from Hungary, providing a significantly larger sample that was available before.
      The uniqueness of our database is linking of two data types that makes possible
      to investigate the bone and skin surface of the same individual, in upright
      position, thus eliminating many of the gravitational effects on the face during
      CT scanning. We performed a preliminary geometric morphometric (GMM) study using
      3D data that produces a general idea of skull and face shape correlations. The
      vertical position of the tip of the (soft) nose for a skull and landmarks such as
      rhinion need to be taken into account. Likewise, the anterior nasal spine appears
      to exert some influence in this regard. 

PMID- 24020395
TI  - Serum 25-hydroxyvitamin D predicts the short-term outcomes of Chinese patients
      with acute ischaemic stroke.
AB  - Low vitamin D levels have been reported to contribute to the risk of
      cardiovascular events and mortality, especially stroke. In the present study we
      therefore evaluated the short-term prognostic value of serum 25(OH)D (25
      hydroxyvitamin D) in Chinese patients with AIS (acute ischaemic stroke). From
      February 2010 to September 2012, consecutive stroke patients admitted to the
      emergency department at two hospitals in Beijing, China were identified. Clinical
      information was collected, and the serum concentration of 25(OH)D and NIHSS
      (National Institutes of Health Stroke Scale) were measured at the time of
      admission. Short-term functional outcome was measured using a modified Rankin
      Scale (mRS) at 90 days after admission. Multivariate analyses were performed
      using logistic regression models. During the inclusion period, 231 patients were
      diagnosed as having AIS, and 220 completed follow-up. The median serum 25(OH)D
      level was significantly lower in patients with AIS compared with normal controls
      [14.2 (10.2-18.9) ng/ml compared with 17.9 (12.5-22.9) ng/ml; P<0.001; values are
      medians (interquartile range)]. 25(OH)D was an independent prognostic marker of
      short-term functional outcome and death {0.79 (0.73-0.85) and 0.70 (0.50-0.98)
      respectively [values are odds rations (95% confidence intervals)]; P<0.01 for
      both, adjusted for NHISS, other predictors and vascular risk factors} in patients
      with AIS. In ROC (receiver operating characteristic) curve analysis, the
      prognostic accuracy of 25(OH)D was higher compared with all of the other serum
      predictors and was in the range of NIHSS score. In conclusion, these findings
      suggest that 25(OH)D is an independent prognostic marker for death and functional
      outcome within 90 days in Chinese patients with AIS even after adjusting for
      possible confounding factors.

PMID- 24020396
TI  - Validation study of Charlson Comorbidity Index in predicting mortality in Chinese
      older adults.
AB  - AIM: The Charlson Comorbidity Index (CCI) is commonly studied for predicting
      mortality, but there is no validation study of it in Chinese older adults. The
      objective of the present study was to validate the use of CCI in Chinese older
      adults for predicting mortality. METHOD: We carried out a retrospective cohort
      study from 2004 to 2013 for patients discharged from a geriatric day hospital in
      Hong Kong. Comorbidity was quantified using CCI, and patients were divided into
      six groups according to their score of CCI: CCI-0, CCI-1, CCI-2, CCI-3, CCI-4 and
      CCI >= 5. Other data collected included demographics, and functional,
      nutritional, cognitive and social assessment. The outcome measure was 1-year
      mortality. RESULTS: At 1-year follow up, 3.8% (n = 17), 5.9% (n = 37), 9.2% (n =
      35), 12.9% (n = 20), 16.9% (n = 23) and 19.3% (n = 60) of CCI-0, CCI-1, CCI-2,
      CCI-3, CCI-4 and CCI >= 5 died, respectively (P < 0.001). Multivariate analysis
      showed that CCI-1, CCI-2, CCI-3, CCI-4 and CCI >= 5 have a hazard ratio (HR) of
      1.34 (confidence interval [CI] 1.04-2.12), 2.18 (CI 1.03-4.61), 3.44 (CI 1.52
      7.81), 3.74 (CI 1.35-10.39) and 4.63 (CI 2.28-9.43), respectively, compared with
      CCI-0. The area under the curve of the receiver operating characteristic curves
      of CCI in predicting 1-year mortality for older adults was 0.68 (CI 0.64-0.72).
      CONCLUSION: There is a significant dose-response relationship in the hazard ratio
      between CCI and 1-year mortality in Chinese older adults, but involvements of
      functional, nutritional and social assessments are important for comprehensive
      quantification of health status in older adults.

PMID- 24020397
TI  - 5-lipoxygenase mRNA and protein isoforms.
AB  - 5-Lipoxygenase (5-LO) catalyses the two initial steps in the biosynthesis of
      leukotrienes, a group of inflammatory lipid mediators derived from arachidonic
      acid. An increased level of leukotrienes is associated with chronic inflammatory
      diseases such as asthma or atherosclerosis. In this MiniReview, we focus on
      recent findings regarding alternative splice variants of 5-LO with a special
      emphasis on two potential protein isoforms expressed in human B-lymphocytes which
      might be of interest as new drug targets. 

PMID- 24020398
TI  - The effects of increased fluid viscosity on swallowing sounds in healthy adults.
AB  - BACKGROUND: Cervical auscultation (CA) is an affordable, non-invasive technique
      used to observe sounds occurring during swallowing. CA involves swallowing
      characterization via stethoscopes or microphones, while accelerometers can detect
      other vibratory signals. While the effects of fluid viscosity on swallowing
      accelerometry signals is well understood, there are still open questions about
      these effects on swallowing sounds. Therefore, this study investigated the
      influence of fluids with increasing thickness on swallowing sound
      characteristics. METHOD: We collected swallowing sounds and swallowing
      accelerometry signals from 56 healthy participants. Each participant completed
      five water swallows, five swallows of nectar-thick apple juice, and five swallows
      of honey-thick apple juice. These swallows were completed in neutral head and
      chin-tuck head positions. After pre-processing of collected signals, a number of
      features in time, frequency and time-frequency domains were extracted. RESULTS:
      Our numerical analysis demonstrated that significant influence of viscosity was
      found in most of the features. In general, features extracted from swallows in
      the neutral head position were affected more than swallows from the chin-tuck
      position. Furthermore, most of the differences were found between water and
      fluids with higher viscosity. Almost no significant differences were found
      between swallows involving nectar-thick and honey-thick apple juices. Our results
      also showed that thicker fluids had higher acoustic regularity and predictability
      as demonstrated by the information-theoretic features, and a lower frequency
      content as demonstrated by features in the frequency domain. CONCLUSIONS:
      According to these results, we can conclude that viscosity of fluids should be
      considered in future investigations involving swallowing sounds.

PMID- 24020399
TI  - Advantageous safety profile of a dual selective alpha(2C) agonist/alpha(2A)
      antagonist antinociceptive agent.
AB  - A selective alpha2C -adrenoceptor (AR) agonist was developed for the treatment of
      neuropathic pain. The objective was to dissociate analgesic activity from
      cardiovascular and sedative side effects commonly observed with nonselective
      agents. A 2-amino-oxazoline derivative (compound A), identified as a dual alpha2C
      -AR agonist/alpha2A -AR antagonist in in vitro-binding assays, exhibited in vivo
      efficacy in rodent pain models. Its safety profile was compared with that of
      clonidine in six different in vivo models. Contrary to clonidine, compound A did
      not induce hypotension in pentobarbital-anesthetized rats, in conscious
      spontaneous hypertensive rats, or in telemetered dogs. Both agents induced
      similar dose-dependent decreases in heart rate in dogs and rats. In anesthetized
      pithed rats, clonidine showed dose-dependent hypertension and inhibited
      electrical nerve stimulation-induced tachycardia at doses close to its
      efficacious doses in the mouse formalin test, while compound A had much weaker
      vasoconstrictive and antichronotropic effects. Finally, in a mouse Irwin test, no
      sedation was observed with compound A at 30-fold its ED50 in the mouse formalin
      test, while sedative effects of clonidine started from three-fold its ED50 .
      These data confirm the advantageous safety profile of the new dual alpha2C -AR
      agonist/alpha2A -AR antagonist agent vs. the nonselective agonist clonidine. 

PMID- 24020400
TI  - Negative correlation between bone mineral density and TSH receptor antibodies in
      long-term euthyroid postmenopausal women with treated Graves' disease.
AB  - BACKGROUND: Thyrotoxicosis is a cause of secondary osteoporosis. High
      concentrations of triiodotironine (T3) in Graves' disease stimulate bone
      turnover, but it is unclear if euthyroidism will always normalize bone
      metabolism. Thyrotropin (TSH) is known to affect directly the bone metabolism
      through the TSH receptor and TSH receptor antibodies (TRAb) may have an important
      role in bone turn-over.The aim of our study was to determine, in pre and
      postmenopausal euthyroidism patients with previous overt hyperthyroidism due to
      Graves' disease the bone mineral density (BMD) as well as factors that could
      affect BMD in each group, including TRAb. METHODS: Cross-sectional, non
      interventional study. Fifty-seven patients with previous hyperthyroidism due to
      Graves' disease (premenopausal: 30, postmenopausal: 27) that remained euthyroid
      for at least 6 months prior to study were included and compared with fifty- two
      matched respective controls. Thyrotoxine (T4), TSH, TRAb and BMD were measured.
      RESULTS: Only euthyroid postmenopausal patients with a history of hyperthyroidism
      due to Graves' disease showed lower whole body BMD than matched controls. The BMD
      expressed as Z-score was less in whole body and lumbar spine in postmenopausal in
      relation to premenopausal women with previous overt hyperthyroidism due to
      Graves' disease.In the postmenopausal patients, the Z-score of lumbar spine BMD
      correlated negatively with TRAb (r = -0,53, p < 0.008), positively with the time
      of evolution of the disease (r = +0.42, p < 0.032) and positively with the time
      of euthyroidism (r = + 0.50, p < 0.008), but neither with serum T4 nor TSH. In a
      multiple regression analysis TRAb was the only significant independent variable
      in relation to lumbar spine BMD (F = 3. 90, p < 0.01). CONCLUSIONS: In euthyroid
      women with a history of Graves' hyperthyroidism, BMD was only affected in the
      postmenopausal group. The negative correlation of Z-score of lumbar spine BMD
      with TRAb suggests that this antibody may affect the bone metabolism.

PMID- 24020401
TI  - Ideal resuscitation pressure for uncontrolled hemorrhagic shock in different ages
      and sexes of rats.
AB  - INTRODUCTION: Our previous studies demonstrated that 50-60 mmHg mean arterial
      blood pressure was the ideal target hypotension for uncontrolled hemorrhagic
      shock during the active hemorrhage in sexually mature rats. The ideal target
      resuscitation pressure for immature and older rats has not been determined.
      METHODS: To elucidate this issue, using uncontrolled hemorrhagic-shock rats of
      different ages and sexes (6 weeks, 14 weeks and 1.5 years representing pre-adult,
      adult and older rats, respectively), the resuscitation effects of different
      target pressures (40, 50, 60, 70 and 80 mmHg) on uncontrolled hemorrhagic shock
      during active hemorrhage and the age and sex differences were observed. RESULTS:
      Different target resuscitation pressures had different resuscitation outcomes for
      the same age and sex of rats. The optimal target resuscitation pressures for 6
      week-old, 14-week-old and 1.5-year-old rats were 40 to 50 mmHg, 50 to 60 mmHg and
      70 mmHg respectively. Ideal target resuscitation pressures were significantly
      superior to other resuscitation pressures in improving the hemodynamics, blood
      perfusion, organ function and animal survival of uncontrolled hemorrhagic-shock
      rats (P < 0.01). For same target resuscitation pressures, the beneficial effect
      on hemorrhagic shock had a significant age difference (P < 0.01) but no sex
      difference (P > 0.05). Different resuscitation pressures had no effect on
      coagulation function. CONCLUSION: Hemorrhagic-shock rats at different ages have
      different target resuscitation pressures during active hemorrhage. The ideal
      target resuscitation hypotension for 6-week-old, 14-week-old and 1.5-year-old
      rats was 40 to 50 mmHg, 50 to 60 mmHg and 70 mmHg, respectively. Their
      resuscitation effects have significant age difference but had no sex difference.

PMID- 24020402
TI  - Heavy metal pollution decreases microbial abundance, diversity and activity
      within particle-size fractions of a paddy soil.
AB  - Chemical and microbial characterisations of particle-size fractions (PSFs) from a
      rice paddy soil subjected to long-term heavy metal pollution (P) and nonpolluted
      (NP) soil were performed to investigate whether the distribution of heavy metals
      (Cd, Cu, Pb and Zn) regulates microbial community activity, abundance and
      diversity at the microenvironment scale. The soils were physically fractionated
      into coarse sand, fine sand, silt and clay fractions. Long-term heavy metal
      pollution notably decreased soil basal respiration (a measurement of the total
      activity of the soil microbial community) and microbial biomass carbon (MBC)
      across the fractions by 3-45% and 21-53%, respectively. The coarse sand fraction
      was more affected by pollution than the clay fraction and displayed a
      significantly lower MBC content and respiration and dehydrogenase activity
      compared with the nonpolluted soils. The abundances and diversities of bacteria
      were less affected within the PSFs under pollution. However, significant
      decreases in the abundances and diversities of fungi were noted, which may have
      strongly contributed to the decrease in MBC. Sequencing of denaturing gradient
      gel electrophoresis bands revealed that the groups Acidobacteria, Ascomycota and
      Chytridiomycota were clearly inhibited under pollution. Our findings suggest that
      long-term heavy metal pollution decreased the microbial biomass, activity and
      diversity in PSFs, particularly in the large-size fractions.

PMID- 24020403
TI  - Experimental rat model for alcohol-induced osteonecrosis of the femoral head.
AB  - Alcohol-induced osteonecrosis of the femoral head (ONFH) is observed in alcohol
      abusers and patients with alcoholic fatty liver disease. It has been reported
      that Toll-like receptor 4 (TLR4) signalling plays a crucial role in the
      pathogenesis of alcoholic fatty liver disease. We previously reported a
      corticosteroid-induced ONFH rat model, and suggested that TLR4 signalling
      contributes to the pathogenesis of ONFH. Thus, it is thought that the
      pathogenesis of alcohol-induced ONFH is probably similar to that of
      corticosteroid-induced ONFH. The aim of this study was to develop a new animal
      model for alcohol-induced ONFH and to evaluate the relationship between the pro
      inflammatory response via TLRs and the development of ONFH in rats. Male Wistar
      rats were fed a Lieber-DeCarli liquid diet containing 5% ethanol (experimental
      group) or dextran (control group) for 1-24 weeks. Histopathological and
      biochemical analyses were performed. Feeding the ethanol-containing liquid diet
      resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction
      and hyperlipidaemia, whereas feeding the dextran-containing diet did not cause
      ONFH. However, we could not recognize any relationship between the pro
      inflammatory response via TLR4 and the development of alcohol-induced ONFH. Thus
      in this study we have developed a new rat model for alcohol-induced ONFH based on
      the feeding of an ethanol liquid diet. ONFH was observed within seven days from
      the start of feeding with 5% ethanol-containing liquid diet. Although this was
      linked to hepatic steatosis, a TLR4 association was not a feature of this model. 

PMID- 24020404
TI  - Disease characteristics of bovine spongiform encephalopathy following inoculation
      into mice via three different routes.
AB  - Mouse-adapted transmissible spongiform encephalopathy (TSE) strains are routinely
      distinguished based on reproducible disease characteristics in a given mouse line
      following inoculation via a consistent route. We investigated whether different
      administration routes (oral, intragastric (i.g.) and intracerebral (i.c.)) can
      alter the disease characteristics in IM mice after serial dilution of a
      stabilized mouse-adapted bovine spongiform encephalopathy (BSE) strain (301V). In
      addition, the infectivity of distal ileum and mesenteric lymph nodes (ln) sampled
      at three time points (35 days postinoculation (dpi), 70 dpi and terminal disease)
      after i.g. inoculation of 301V strain was assessed in mice by i.c. challenge.
      Strain characteristics were assessed according to standard methodology and
      PrP(Sc) immunohistochemistry deposition patterns. Mean incubation periods were
      prolonged following oral or i.g. inoculations compared to the i.c. route. Lesion
      profiles following i.c. challenges were elevated compared to i.g. and oral routes
      although vacuolation in the dorsal medulla was consistently high irrespective of
      the route of administration. Nevertheless, the same PrP(Sc) deposition pattern
      was associated with each route of administration. Distal and mesenteric ln
      infectivity was detected as early as 35 dpi and displayed consistent lesion
      profiles and PrP(Sc) deposition patterns. Our data suggest that although 301V
      retained its properties, some phenotypic parameters were affected by the route of
      inoculation. We conclude that bioassay data should be interpreted carefully and
      should be standardized for route of inoculation. 

PMID- 24020405
TI  - Evaluation of autologous blood clot subsegmental pulmonary thromboembolism in
      minimally invasive experimental canine model.
AB  - The incidence and significance of subsegmental pulmonary (SSP) thromboembolism is
      currently under investigation. We aimed to evaluate the clinical and diagnostic
      features of SSP thromboembolism in an experimental canine model. Obstruction of
      pulmonary arterial branches was induced in three beagle dogs by intravenous
      injection of a barium-coated autologous blood clot (size, approximately 1.7 * 5
      mm). The clinical signs, haemodynamic changes (blood pressure, electrocardiogram,
      echocardiography), coagulation (aPTT, PT, FDPs and D-dimer test) and cytokine
      variations (TNF-a, IL-4, IL-6, and IL-10) were evaluated over a 24-hour period.
      Multidetector computed tomography (MDCT) with contrast was conducted to evaluate
      the pulmonary obstruction, and histopathological confirmation was performed.
      Pulmonary artery pressure gradient (PAPG) was increased 12 h after the autologous
      blood clot injection (14.2 +/- 2.8 mmHg to 23.6 +/- 1.7 mmHg, P = 0.003) and
      normalized 24 h later (P < 0.01). Infused radiopaque clots were confirmed with
      MDCT and histopathological examination. Pulmonary parenchymal changes such as
      arterial dilation and inflammatory reactions were also confirmed in
      histopathological examinations and were barely observable in MDCT. Usually small
      emboli are not easily detected through CT imaging, and the clinical relevance of
      these emboli is controversial. In this experimental study, we made radiopaque
      small emboli and induced SSP thromboembolism. Thus, we infer that obstruction of
      the small segmental and subsegmental pulmonary arteries does result in a
      pulmonary thromboembolism (PTE) and PTE-related pulmonary parenchymal changes
      which could be clinically significant. 

PMID- 24020406
TI  - Cardiomyocyte ultrastructural damage in beta-thalassaemic mice.
AB  - beta-thalassaemia is a hereditary anaemia resulting from the absence or reduction
      in beta-globin chain production. Heart complications related to iron overload are
      the most serious cause of death in these patients. In this report cardiac
      pathology of beta-thalassaemic mice was evaluated by light and electron
      microscopy. The study was carried out in thalassaemic mice carrying human beta
      thalassaemia mutation, IVSII-654 (654), transgenic mice carrying human beta(E) 
      globin transgene insertion (E4), thalassaemic mice with human beta(E) -globin
      transgene insertion (654/E4) and homozygous thalassaemic mice rescued by the
      human beta(E) -globin transgene (R), which is generated by cross-breeding between
      the 654 and E4 mice. Histology showed iron deposition in cardiac myocytes of 654
      and R mice, but the ultrastructural damage was observed only in the R mice when
      compared with the wild type, 654, E4 and 654/E4 mice. Histopathological changes
      in the cardiomyocytes of the R mice included mitochondrial swelling, loss of
      myofilaments and the presence of lipofuscin, related to the increased level of
      tissue iron content. The progressive ultrastructural pathology in R mice
      cardiomyocytes is consistent with the ultrastructural pathology previously
      studied in patients with thalassaemia. Thus, this R thalassaemic mouse model is
      suitable for in vivo pathophysiological study of thalassaemic heart. 

PMID- 24020407
TI  - Long-lasting morphofunctional remodelling of liver parenchyma and stroma after a
      single exposure to low and moderate doses of cadmium in rats.
AB  - Frequent exposure to cadmium (Cd) in low doses is common; however, the long
      lasting effects of this exposure are still poorly understood. Therefore in this
      study we have evaluated long-lasting hepatic morphofunctional adaptations in rats
      exposed to low and moderate doses of Cd. Five experimental groups were tested:
      control (0.9% saline) and other four receiving single intraperitoneal doses of
      0.67, 0.74, 0.86 and 1.1 mg of Cd/kg. The animals were killed after eight weeks
      and the following parameters were analysed: biometrics, oedema, Cd bio
      accumulation, collagen, glycogen, lipid droplets, superoxide dismutase (SOD) and
      catalase (CAT), serum transaminases, liver histopathology and stereology. In all
      groups exposed to Cd there was significant increase in SOD and CAT activities,
      ALP levels, proportion of binucleated hepatocytes, nuclei/cytoplasm ratio,
      macrophages (Kupffer cells) and collagen fibres. In these groups, glycogen
      accumulation by hepatocytes and the proportion of sinusoidal capillaries were
      significantly reduced compared with controls. The liver somatic index was
      increased, and liver oedema was evident in animals exposed to higher dose of Cd.
      Areas of necrosis were found in animals exposed to the three highest doses. These
      results indicate that Cd is an extremely toxic bioactive heavy metal, which even
      at low doses is able to disrupt liver homeostasis. At low and moderate doses, Cd
      exposure induces morphofunctional pathological remodelling of the hepatic stroma
      and parenchyma, which remain active after eight weeks. In response to injury, the
      liver tissue triggers a reactive process by enhancing activation of antioxidant
      enzymes and collagenogenesis. 

PMID- 24020408
TI  - Mitochondrial DNA depletion may also have a role in pathogenesis of osteosarcoma.

PMID- 24020409
TI  - Authors' reply.

PMID- 24020411
TI  - Modelling mutational and selection pressures on dinucleotides in eukaryotic phyla
      -selection against CpG and UpA in cytoplasmically expressed RNA and in RNA
      viruses.
AB  - BACKGROUND: Loss of CpG dinucleotides in genomic DNA through methylation-induced
      mutation is characteristic of vertebrates and plants. However, these and other
      eukaryotic phyla show a range of other dinucleotide frequency biases with
      currently uncharacterized underlying mutational or selection mechanisms. We
      developed a parameterized Markov process to identify what neighbour context
      dependent mutations best accounted for patterns of dinucleotide frequency biases
      in genomic and cytoplasmically expressed mRNA sequences of different vertebrates,
      other eukaryotic groups and RNA viruses that infect them. RESULTS: Consistently,
      11- to 14-fold greater frequencies of the methylation-associated mutation of C to
      T upstream of G (depicted as C->T,G) than other transitions best modelled
      dinucleotide frequencies in mammalian genomic DNA. However, further mutations
      such as G->T,T (5-fold greater than the default transversion rate) were required
      to account for the full spectrum of dinucleotide frequencies in mammalian
      sequence datasets. Consistent with modeling predictions for these two mutations,
      instability of both CpG and CpT dinucleotides was identified through SNP
      frequency analysis of human DNA sequences. Different sets of context-dependent
      mutations were modelled in other eukaryotes with non-methylated genomic DNA. In
      contrast to genomic DNA, best-fit models of dinucleotide frequencies in
      transcribed RNA sequences expressed in the cytoplasm from all organisms were
      dominated by mutations that eliminated UpA dinucleotides, observations consistent
      with cytoplasmically driven selection for mRNA stability. Surprisingly, mRNA
      sequences from organisms with methylated genomes showed evidence for additional
      selection against CpG through further context-dependent mutations (eg. C->A,G).
      Similar mutation or selection processes were identified among single-stranded
      mammalian RNA viruses; these potentially account for their previously described
      but unexplained under-representations of CpG and UpA dinucleotides. CONCLUSIONS:
      Methods we have developed identify mutational processes and selection pressures
      in organisms that provide new insights into nucleotide compositional constraints
      and a wealth of biochemical and evolutionarily testable predictions for the
      future.

PMID- 24020412
TI  - Pancreatic lipase inhibitory stilbenoids from the roots of Vitis vinifera.
AB  - Bioassay-guided isolation of an aqueous methanolic extract of Vitis vinifera
      using pancreatic lipase inhibitory activity led to isolation of seven
      stilbenoids, wilsonol C (1), heyneanol A (2), ampelopsin A (3), pallidol A (4),
      cis-piceid (5), trans-piceid (6) and trans-resveratrol (7). The structures were
      established on the basis of NMR and MS spectroscopic data interpretation. All
      isolates were evaluated for their inhibitory effects on pancreatic lipase, and
      stilbenoid 1 exhibited potent inhibitory effect on pancreatic lipase with IC50
      values of 6.7 +/- 0.7 uM.

PMID- 24020413
TI  - Olfactory dysfunction in pediatric traumatic brain injury: a systematic review.
AB  - The neuropsychological outcomes of pediatric traumatic brain injury (TBI) have
      received increasing study over the past 20 years and are currently well
      delineated in the research literature. One outcome that has received little
      attention is that of olfactory dysfunction after pediatric TBI. This is despite
      literature indicating that anosmia and olfactory dysfunction are common after
      adult TBI and are likely to be linked to severity of injury, neuropathology, and
      executive dysfunction. At a clinical level, anosmia is known to be reported after
      pediatric TBI. Despite this, little is known about its prevalence and recovery. A
      systematic review was undertaken to provide objective information about olfactory
      dysfunction post-TBI in children. Despite broad inclusion criteria, only four
      published studies were identified. The studies found were limited by
      methodological weaknesses, variability in measures, small sample size, and
      difficulty of comparison across cohorts studied. Despite this, they reported
      consistent findings of anosmia and olfactory dysfunction in their TBI cohorts and
      identified a dose-response relationship between severity of injury and olfactory
      dysfunction. The results of the studies are discussed in terms of relevant
      findings, limitations, and areas requiring further exploration.

PMID- 24020414
TI  - Functionalized pentamolybdodiphosphate-based inorganic-organic hybrids:
      synthesis, structure, and properties.
AB  - Three inorganic-organic hybrid compounds based on functionalized
      pentamolybdodiphosphonopropionate anion [(HO2CC2H4PO3)2Mo5O15](4-),
      [Co3(bipy)4(H2O)6{(HO2CC2H4PO3)2Mo5O15}2].(H2bipy)2.18H2O (1),
      [Fe3(bipy)4(H2O)6{(HO2CC2H4PO3)2Mo5O15}2].(H2bipy)2.18H2O (2), and
      [Cu(bipy)(H2O)2{(HO2CC2H4PO3)2Mo5O15}].(H2bipy).4H2O (3), where bipy = 4,4'
      bipyridine, have been successfully synthesized at different pH values in aqueous
      solutions. In compound 1, [(HO2CC2H4PO3)2Mo5O15](4-) acts as a tridentate ligand
      and coordinates to the Co(2+) ions of trimeric complex cations
      [Co3(bipy)4(H2O)6](6+) forming a layer. In 3 [(HO2CC2H4PO3)2Mo5O15](4-) acts as a
      bidentate ligand and coordinates to the Cu(2+) ions of complex chains
      [Cu(bipy)(H2O)2]n(2n+), forming a different layer from that in 1. The three
      compounds were characterized by elemental analysis, IR spectra, and TGA. In
      addition, their fluorescent properties and magnetic properties have also been
      investigated. 

PMID- 24020422
TI  - Synthesis and properties of electrically conductive, ductile, extremely long (~50
      MUm) nanosheets of K(x)CoO2.yH2O.
AB  - Extremely long, electrically conductive, ductile, free-standing nanosheets of
      water-stabilized KxCoO2.yH2O are synthesized using the sol-gel and electric-field
      induced kinetic-demixing (SGKD) process. Room temperature in-plane resistivity of
      the KxCoO2.yH2O nanosheets is less than ~4.7 mOmega.cm, which corresponds to one
      of the lowest resistivity values reported for metal oxide nanosheets. The
      synthesis produces tens of thousands of very high aspect ratio (50,000:50,000:1 =
      length/width/thickness), millimeter length nanosheets stacked into a macro-scale
      pellet. Free-standing nanosheets up to ~50 MUm long are readily delaminated from
      the stacked nanosheets. High-resolution transmission electron microscopy (HR-TEM)
      studies of the free-standing nanosheets indicate that the delaminated pieces
      consist of individual nanosheet crystals that are turbostratically stacked. X-ray
      diffraction (XRD) studies confirm that the nanosheets are stacked in perfect
      registry along their c-axis. Scanning electron microscopy (SEM) based statistical
      analysis show that the average thickness of the nanosheets is ~13 nm. The
      nanosheets show ductility with a bending radius as small as ~5 nm.

PMID- 24020423
TI  - Size-dependent photoionization in single CdSe/ZnS nanocrystals.
AB  - Fluorescence intermittency in single semiconductor nanocrystals has been shown to
      follow power law statistics over many decades in time and in probability.
      Recently, several studies have shown that, while "off" dwell times are
      insensitive to almost all experimental parameters, "on" dwell times exhibit a
      pump-power dependent exponential truncation at long times, suggestive of enhanced
      biexciton photoionization probabilities at high excitation powers. Here we report
      the dependence of this on-time truncation on nanocrystal radius. We observe a
      decrease in the per-pulse photoionization probability from 1.8(2) * 10(-4) to
      2.0(7) * 10(-6) as the CdSe core radius increases from 1.3 to 3.5 nm, with a
      radius scaling for the probability for charge ejection arising from biexciton
      formation P(ionize)(r) is proportional to 1/r(3.5(5)). Effective mass
      calculations of the exciton wave functions show that the product of fractional
      electron and hole probabilities in the trap-rich ZnS shell scale similarly with
      nanocrystal radius. Possible charge ejection mechanisms from such a surface
      localized state are discussed.

PMID- 24020424
TI  - A comprehensive exercise program for a young adult male with Down syndrome who
      experienced a stroke.
AB  - PURPOSE: Individuals with Down syndrome (DS) may be at heightened risk for stroke
      due to a combination of physiological conditions and lifestyle choices. There
      remains a lack of information regarding the effectiveness of exercise training on
      individuals with DS post-stroke. This case report describes the effects of a
      comprehensive exercise program on an individual with DS who had sustained a
      stroke. METHOD: A 20-year-old male with DS recovering from a left hemorrhagic
      stroke 18 months previous underwent a 12-week land and water-based program 60
      minutes/session, 5 sessions/week. Exercise sessions addressed specific
      limitations, including cardiorespiratory fitness, generalized muscle weakness,
      balance deficits, and reduced ambulatory ability in terms of speed, gait pattern
      and walking tolerance. RESULTS: Between the baseline and 6-month follow-up
      assessments improvements were noted in peak oxygen consumption (VO2peak, 8%
      increase), one-repetition maximum (51%), community balance and mobility scale
      (54%), comfortable walking speed (42%), six-minute walk test (28%) and daily step
      count (21%). CONCLUSION: Improved cardiorespiratory fitness, strength, balance
      and mobility provide preliminary evidence of the trainability of individuals with
      both DS and stroke. Future studies are warranted to investigate the role of
      exercise in risk factor reduction for primary and secondary prevention of stroke
      in people with DS. Implications for Rehabilitation Individuals with Down syndrome
      (DS) may be at heightened risk of stroke due to a combination of physiological
      conditions and lifestyle choices which contribute to reduced exercise capacity,
      accelerated aging patterns, moyamoya syndrome and physical inactivity as well as
      high rates of obesity and related conditions. More intensive fitness programs may
      be particularly important for people with both DS and stroke. Participation in a
      comprehensive exercise program can be safe and effective in regaining pre-stroke
      levels of cardiorespiratory fitness, functional mobility and goal attainment.
      RESULTS suggest that a more intensive physical therapy regimen may be
      recommendable during out-patient rehabilitation for individuals with DS post
      stroke.

PMID- 24020426
TI  - "It gave me something big in my life to wonder and think about which took over
      the space ... and not MS": managing well-being in multiple sclerosis through art
      making.
AB  - BACKGROUND AND AIM: Individuals living with Multiple Sclerosis (MS) often face
      progressive loss of function, uncertainty and disruption to self-image and valued
      roles. Previous studies show that creative self-expression is valued by some
      people living with long-term illness, yet its meaning for people living with MS
      is unclear. This research study explored the meanings of leisure-based visual art
      making for people living with MS. METHOD: This qualitative study followed
      guidelines for Interpretative Phenomenological Analysis (IPA). Single semi
      structured interviews were conducted with five adults (2 males; 3 females; 40-65
      years), recruited from MS Ireland. FINDINGS: Participants valued art-making for
      contributing to a more satisfying way of life; for filling occupational voids and
      using time well. Deep immersion offered respite from worry about illness.
      Creative classes offered social camaraderie and opportunities for learning and
      development. Art-making processes and products were highly affirmative,
      increasing emotional well-being and promoting self-worth. Most felt that they
      expressed valued aspects of self through their art. Art-making appeared to assist
      with identity maintenance, accommodating functional losses associated with MS
      whilst opening "new doors". CONCLUSION: Art-making offered a multi-faceted means
      of supporting identity and increasing fulfilment in lives that were restricted in
      many ways by MS.

PMID- 24020425
TI  - Exercise testing as a screening measure for ability to walk with aprosthesis
      after transfemoral amputation due to peripheral vascular disease.
AB  - PURPOSE: To establish at which exercise-power level is the vascular response, as
      measured by oxygen uptake, closest to the response during the 6-min walk test (6
      MWT) in people after lower-limb amputation due to peripheral vascular disease
      (PVD). METHOD: A prospective exploratory cohort study was conducted. 6 MWT and
      exercise testing using a hand-wheel ergometer (starting at 10 W and increasing
      the workload by 10 W) were performed in 101 consecutively recruited participants
      after transfemoral amputation due to PVD. Agreement of oxygen uptake during 6 MWT
      and exercise testing was compared between the groups defined by the exercise
      power level reached. RESULTS: Linear regression through origin with Chow test for
      comparing slopes indicated that oxygen uptake at 30 W agreed more with 6 MWT than
      at 20, 40 or 50 W. Analyses of observed differences (one-way ANOVA with post-hoc
      tests, Jonckheere-Terpstra test) confirmed 30 W to be the recommendable
      threshold. CONCLUSIONS: At the level of 30 W, the oxygen uptake during the
      exercise was the closest to the 6 MWT, so we estimated that to be the minimum
      required level for walking using a prosthesis after transfemoral amputation due
      to PVD. Implications for Rehabilitation Exercise testing after transfemoral
      amputation. Walking with a prosthesis causes notable strain to the person's
      vascular system: after the 6-min walk test, the participants' heart rate reached
      75% of the maximum predicted heart rate on average. The study shows that persons
      after transfemoral amputation due to peripheral vascular disease who reach the
      level of 30 W or more in exercise testing with an arm ergometer at admission to
      rehabilitation are likely to be able to walk in-doors using a prosthesis.

PMID- 24020427
TI  - 3-Chloro-1-lithiopropene, a functional organolithium reagent, and its reactions
      with alkylboronates to give 3-alkylprop-1-en-3-ols.
AB  - The reagent 3-chloro-1-lithiopropene (4) can be generated by treating 1-bromo-3
      chloropropene with t-BuLi. It is unstable but if generated at low temperature in
      the presence of alkylboronic esters, such as 3, is trapped in situ to give
      rearrangement products 2, which on oxidation give 3-alkylprop-1-en-3-ols in good
      yields. The reaction works for primary, secondary, benzylic, and even tertiary
      alkylboronic esters, providing allylic alcohols bearing almost any alkyl group
      available using organoborane chemistry and incorporating all features of such
      groups. 

PMID- 24020428
TI  - Dynamics in glass forming sulfuric and nitric acid hydrates.
AB  - Deuteron nuclear magnetic resonance (NMR) and dielectric spectroscopy are
      utilized to investigate the dynamics in sulfuric acid hydrates as well as in
      nitric acid hydrates for various degrees of hydration. Near the glass transition
      temperature the electrical response is up to four decades faster than the
      calorimetric one, a feature found also for several other inorganic ionic liquids.
      The acid hydrates display pronounced super-Arrhenius behavior with fragility
      indices of the order of 100. The relaxation strength of the acid hydrates
      increases with increasing temperature, an observation that was rationalized with
      reference to the degree of molecular dissociation. Spin relaxometry and
      stimulated-echo spectroscopy revealed an overall isotropic reorientation process
      featuring a jump angle of about 30 degrees . Finally, the implications of the
      present results for the understanding of the glass transition of pure
      ultraviscous water are discussed. 

PMID- 24020429
TI  - Genotypic polymorphisms of hepatitis B virus provide useful information for
      estimating geographical origin or place of long-term residence of unidentified
      cadavers.
AB  - Increasing numbers of unidentified cadavers are a major problem. We have
      developed a new method for providing identification information that can
      determine the geographical origin or place of long-term residence of unidentified
      cadavers based on genotypic polymorphisms of hepatitis B virus (HBV) known to
      correlate with their geographical distribution. PCR of serum samples detected HBV
      DNA from 4 (3.9%) of 102 randomly selected Japanese forensic cadavers. Multiplex
      PCR did not detect multiple HBV genotypes from any single cadaver, confirming the
      absence of coinfection. Phylogenetic tree analysis based on a 485-bp mutant
      region of the HBV S gene successfully classified the HBV genotypes into A to J.
      Among 10 HBV-infected cadavers, 8 had genotype Ce/C2, a genotype prevalent in
      East Asia, and 2 had genotype Bj/B1, a Japanese-specific genotype. HBV genotypic
      polymorphisms correlate with the geographical distribution of the virus and thus
      provide important information for identifying unidentified cadavers infected with
      HBV. 

PMID- 24020431
TI  - Elevating bioavailability of curcumin via encapsulation with a novel formulation
      of artificial oil bodies.
AB  - Utilization of curcumin has been limited due to its poor oral bioavailability.
      Oral bioavailability of hydrophobic compounds might be elevated via encapsulation
      in artificial seed oil bodies. This study aimed to improve oral bioavailability
      of curcumin via this encapsulation. Unfortunately, curcumin was indissoluble in
      various seed oils. A mixed dissolvent formula was used to dissolve curcumin, and
      the admixture was successfully encapsulated in artificial oil bodies stabilized
      by recombinant sesame caleosin. The artificial oil bodies of relatively small
      sizes (150 nm) were stably solidified in the forms of powder and tablet. Oral
      bioavailability of curcumin with or without encapsulation in artificial oil
      bodies was assessed in Sprague-Dawley male rats. The results showed that
      encapsulation of curcumin significantly elevated its bioavailability and provided
      the highest maximum whole blood concentration (Cmax), 37 +/- 28 ng/mL, in the
      experimental animals 45 +/- 17 min (t(max)) after oral administration. Relative
      bioavailability calculated on the basis of the area under the plasma
      concentration-time curve (AUC) was increased by 47.7 times when curcumin was
      encapsulated in the artificial oil bodies. This novel formulation of artificial
      oil bodies seems to possess great potential to encapsulate hydrophobic drugs for
      oral administration.

PMID- 24020432
TI  - Estimation of adequate setup margins and threshold for position errors requiring
      immediate attention in head and neck cancer radiotherapy based on 2D image
      guidance.
AB  - BACKGROUND: We estimated sufficient setup margins for head-and-neck cancer (HNC)
      radiotherapy (RT) when 2D kV images are utilized for routine patient setup
      verification. As another goal we estimated a threshold for the displacements of
      the most important bony landmarks related to the target volumes requiring
      immediate attention. METHODS: We analyzed 1491 orthogonal x-ray images utilized
      in RT treatment guidance for 80 HNC patients. We estimated overall setup errors
      and errors for four subregions to account for patient rotation and deformation:
      the vertebrae C1-2, C5-7, the occiput bone and the mandible. Setup margins were
      estimated for two 2D image guidance protocols: i) imaging at first three
      fractions and weekly thereafter and ii) daily imaging. Two 2D image matching
      principles were investigated: i) to the vertebrae in the middle of planning
      target volume (PTV) (MID_PTV) and ii) minimizing maximal position error for the
      four subregions (MIN_MAX). The threshold for the position errors was calculated
      with two previously unpublished methods based on the van Herk's formula and
      clinical data by retaining a margin of 5 mm sufficient for each subregion.
      RESULTS: Sufficient setup margins to compensate the displacements of the
      subregions were approximately two times larger than were needed to compensate
      setup errors for rigid target. Adequate margins varied from 2.7 mm to 9.6 mm
      depending on the subregions related to the target, applied image guidance
      protocol and early correction of clinically important systematic 3D displacements
      of the subregions exceeding 4 mm. The MIN_MAX match resulted in smaller margins
      but caused an overall shift of 2.5 mm for the target center. Margins <= 5mm were
      sufficient with the MID_PTV match only through application of daily 2D imaging
      and the threshold of 4 mm to correct systematic displacement of a subregion.
      CONCLUSIONS: Adequate setup margins depend remarkably on the subregions related
      to the target volume. When the systematic 3D displacement of a subregion exceeds
      4 mm, it is optimal to correct patient immobilization first. If this is not
      successful, adaptive replanning should be considered to retain sufficiently small
      margins.

PMID- 24020435
TI  - Abstracts of the Australian Gastroenterology Week 2013. October 7-9, 2013.
      Melbourne, Victoria, Australia.

PMID- 24020433
TI  - Pain reports and pain medication treatment in nursing home residents with and
      without dementia.
AB  - AIM: The purpose of this pilot study was to determine if a diagnosis of dementia
      influenced pain self-reports and pain medication use in a group of verbally
      communicative nursing home (NH) residents. METHODS: The study design was a
      between groups, cross-sectional chart audit and a seven-question structured pain
      interview comparing outcomes in residents with and without a diagnosis of
      dementia. The study was carried out at a large metropolitan NH in the southern
      USA. The participants consisted of 52 long-stay NH residents capable of self
      consent with at least one order for pain medication (opioid or non-narcotic)
      either pro re nata, scheduled or both. Approximately 40% (n = 20) had a diagnosis
      of dementia. RESULTS: Although each group had similar pain-related diagnoses,
      residents without a dementia diagnosis were significantly more likely to have a
      medication order for an opioid (OR 4.37,95% CI 1.29-14.73, P = 0.018). Based on
      self-reported pain interview responses, no statistically significant differences
      were identified between the groups for chronic pain symptoms. However, among
      residents who reported current pain, those with a dementia diagnosis reported
      greater pain intensity (based on a 0-10 numeric rating scale) than did those
      without dementia (median 8.0 vs 6.0, respectively; P = 0.010). CONCLUSIONS:
      Verbally communicative NH residents with mild and moderate cognitive impairment
      can report their pain symptoms and pain intensity. Nurses in long-term care might
      assume that residents with dementia cannot reliably self-report their pain;
      however, suffering from untreated severe pain could exacerbate cognitive
      impairment, worsen functional impairment and severely impair sleep. A brief,
      focused pain interview might be one method for increasing the detection of
      moderate to severe pain in verbally communicative NH residents with dementia.

PMID- 24020438
TI  - Comparative genomics of actinomycetes with a focus on natural product
      biosynthetic genes.
AB  - BACKGROUND: Actinomycetes are a diverse group of medically, industrially and
      ecologically important bacteria, studied as much for the diseases they cause as
      for the cures they hold. The genomes of actinomycetes revealed that these
      bacteria have a large number of natural product gene clusters, although many of
      these are difficult to tie to products in the laboratory. Large scale comparisons
      of these clusters are difficult to perform due to the presence of highly similar
      repeated domains in the most common biosynthetic machinery: polyketide synthases
      (PKSs) and nonribosomal peptide synthetases (NRPSs). RESULTS: We have used
      comparative genomics to provide an overview of the genomic features of a set of
      102 closed genomes from this important group of bacteria with a focus on natural
      product biosynthetic genes. We have focused on well-represented genera and
      determine the occurrence of gene cluster families therein. Conservation of
      natural product gene clusters within Mycobacterium, Streptomyces and Frankia
      suggest crucial roles for natural products in the biology of each genus. The
      abundance of natural product classes is also found to vary greatly between
      genera, revealing underlying patterns that are not yet understood. CONCLUSIONS: A
      large-scale analysis of natural product gene clusters presents a useful
      foundation for hypothesis formulation that is currently underutilized in the
      field. Such studies will be increasingly necessary to study the diversity and
      ecology of natural products as the number of genome sequences available continues
      to grow.

PMID- 24020439
TI  - A systematic review of psychosocial outcomes within 2 years of paediatric
      traumatic brain injury in a school-aged population.
AB  - PRIMARY OBJECTIVE: To systematically review the results of investigative research
      into psychosocial outcomes following paediatric traumatic brain injury (TBI) in
      children of school-age. METHODS: Searches were conducted using PsycINFO, MEDLINE
      and Science Direct. Three hundred and ninety papers were identified, of which 17
      met inclusion criteria. Citation searches uncovered 28 further studies. All 44
      studies were appraised in terms of their methodological rigour (e.g. sample
      characteristics, measures utilized, control groups employed). RESULTS: The papers
      reviewed described outcomes across domains of behavioural, emotional, adaptive
      and parent/family functioning. Studies describing behavioural functioning post
      injury demonstrated least consistent results. Papers examining emotional,
      adaptive and parent/family outcomes found that those with head injury presented
      with poorer functioning than other paediatric populations. Injury severity was
      commonly identified as a significant predictor of outcome, as were several pre
      injury psychosocial factors. CONCLUSIONS: Inconsistencies in results may have
      arisen due to the heterogeneous populations studied and methodologies employed.
      Research which examines the reliability of assessment measures is needed. Given
      the high prevalence of difficulties, psychosocial assessment is warranted in this
      population.

PMID- 24020440
TI  - Further development of the response scales of the Acquired Brain Injury Challenge
      Assessment (ABI-CA).
AB  - PRIMARY OBJECTIVE: To revise the scaling of the response sets of the Acquired
      Brain Injury Challenge Assessment (ABI-CA) through expert input and determination
      of empirically based cut-points. RESEARCH DESIGN: A measurement development study
      with a content validity focus. METHODS: Response option wording was revised
      through consultation with six physiotherapists with paediatric ABI expertise.
      Twenty-nine typically-developing children performed the ABI-CA and empirically
      based cut-points for item-specific response options were derived from their
      time/distance/repetition results (SD values) as benchmark values. Movement
      quality considerations (compensatory movements) were identified from expert
      consultation/ABI-CA video observation and built into revised response options.
      The revised ABI-CA was pilot-tested with four children with ABI, aged 7-15 years,
      for a feasibility check. RESULTS: Nineteen of the 23 items' response scales were
      revised based on experts' feedback and empirically-based cut-points replaced the
      previous arbitrarily-determined cut-points. Compensatory movement considerations
      were re-defined in nine items. The mean score of the refined ABI-CA was 70.0% (SD
      = 18.5) with four children with ABI. CONCLUSION: The new response options in the
      ABI-CA appeared suitable for testing high-functioning children with ABI and the
      mid-range mean score in this pilot sample indicates its potential to measure
      change. Recommendations are outlined for final ABI-CA amendments before large
      scale validation.

PMID- 24020441
TI  - The influence of TBI impairments on family caregiver mental health in Mexico.
AB  - PURPOSE: This study examined the influence of five types of impairments in
      individuals with traumatic brain injury (TBI)-and caregiver stress due to these
      impairments-on the mental health of family caregivers in Guadalajara, Mexico.
      METHOD: Ninety caregivers completed measures of TBI impairments and of their own
      mental health. The majority were female (92.20%) with a mean age of 47.12 years
      (SD = 12.67). Caregivers dedicated a median of 50 hours weekly to caregiving and
      had spent a median of 11 months providing care. RESULTS: Two canonical
      correlation analyses suggested that these two sets of variables were broadly
      related, such that more severe impairments in individuals with TBI and more
      caregiver stress due to those impairments were associated with lower caregiver
      mental health. Across both analyses, social impairments were most associated with
      increased caregiver burden. Follow-up analyses also uncovered that caregiver
      stress due to cognitive impairments was uniquely associated with caregiver burden
      and anxiety. CONCLUSIONS: These results are the first to provide evidence that
      social and cognitive impairments in individuals with TBI from Latin America are
      the impairments most associated with caregiver mental health and highlight the
      need for interventions that target social and cognitive functioning.

PMID- 24020443
TI  - Temporal changes in particle-associated microbial communities after interception
      by nonlethal sediment traps.
AB  - Using marine sediment traps (named RESPIRE for REspiration of Sinking Particles
      In the subsuRface ocEan) designed to collect sinking particles and associated
      microbial communities in situ, we collected and incubated marine
      aggregates/particles in the southern Pacific Ocean from separate phytoplankton
      bloom events in situ. We determined the phylogenetic affiliation for the
      microorganisms growing on aggregates by pyrosequencing partial 16S rRNA gene
      amplicons. Water column samples were also collected and sequenced for comparison
      between sinking-particle-associated and planktonic bacterial communities.
      Statistically significant differences were found between the water column and
      sediment trap bacteria. Relative abundances of Pelagibacter sp. and multiple
      members of the Flavobacteria, Actinobacteria, and alpha-Proteobacteria were
      elevated in water column samples, while trap samples contained members of the
      Roseobacter clade of alpha-Proteobacteria in high relative abundances. Our
      findings indicated that rapid changes - within 24 h of collection - occurred to
      the microbial community associated with aggregates from either bloom type. There
      was a little change in the bacterial assemblage after the initial 24-h incubation
      period. The most abundant early colonizer was a Sulfitobacter sp. This study
      provides further evidence that Roseobacters are rapid colonizers of marine
      aggregates and that colonization can occur on short timescales. This study
      further demonstrates that particle origin may be insignificant regarding the
      heterotrophic bacterial population that degrades them.

PMID- 24020442
TI  - Changes in intrinsic functional brain networks following blast-induced mild
      traumatic brain injury.
AB  - OBJECTIVE: Blast-induced mild traumatic brain injuries (mTBI) commonly go
      undetected by computed tomography and conventional magnetic resonance imaging
      (MRI). This study was used to investigate functional brain network abnormalities
      in a group of blast-induced mTBI subjects using independent component analysis
      (ICA) of resting state functional MRI (fMRI) data. METHODS: Twenty-eight resting
      state networks of 13 veterans who sustained blast-induced mTBI were compared with
      healthy controls across three fMRI domains: blood oxygenation level-dependent
      spatial maps, time course spectra and functional connectivity. RESULTS: The mTBI
      group exhibited hyperactivity in the temporo-parietal junctions and hypoactivity
      in the left inferior temporal gyrus. Abnormal frequencies in default-mode (DMN),
      sensorimotor, attentional and frontal networks were detected. In addition,
      functional connectivity was disrupted in six network pairs: DMN-basal ganglia,
      attention-sensorimotor, frontal-DMN, attention-sensorimotor, attention-frontal
      and sensorimotor-sensorimotor. CONCLUSIONS: The results suggest white matter
      disruption across certain attentional networks. Additionally, given their
      elevated activity relative to controls', the temporo-parietal junctions of blast
      mTBI subjects may be compensating for diffuse axonal injury in other cortical
      regions.

PMID- 24020444
TI  - Advances in our understanding of the pathophysiology of Type 1 diabetes: lessons
      from the NOD mouse.
AB  - T1D (Type 1 diabetes) is an autoimmune disease caused by the immune-mediated
      destruction of pancreatic beta-cells. Studies in T1D patients have been limited
      by the availability of pancreatic samples, a protracted pre-diabetic phase and
      limitations in markers that reflect beta-cell mass and function. The NOD (non
      obese diabetic) mouse is currently the best available animal model of T1D, since
      it develops disease spontaneously and shares many genetic and immunopathogenic
      features with human T1D. Consequently, the NOD mouse has been extensively studied
      and has made a tremendous contribution to our understanding of human T1D. The
      present review summarizes the key lessons from NOD mouse studies concerning the
      genetic susceptibility, aetiology and immunopathogenic mechanisms that contribute
      to autoimmune destruction of beta-cells. Finally, we summarize the potential and
      limitations of immunotherapeutic strategies, successful in NOD mice, now being
      trialled in T1D patients and individuals at risk of developing T1D. 

PMID- 24020445
TI  - Septic shock: desperately seeking treatment.
AB  - Septic shock results from the dysregulation of the innate immune response
      following infection. Despite major advances in fundamental and clinical research,
      patients diagnosed with septic shock still have a poor prognostic outcome, with a
      mortality rate of up to 50%. Indeed, the reasons leading to septic shock are
      still poorly understood. First postulated 30 years ago, the general view of
      septic shock as an acute and overwhelming inflammatory response still prevails
      today. Recently, the fact that numerous clinical trials have failed to
      demonstrate any positive medical outcomes has caused us to question our
      fundamental understanding of this condition. New and sophisticated technologies
      now allow us to accurately profile the various stages and contributory components
      of the inflammatory response defining septic shock, and many studies now report a
      more complex inflammatory response, particularly during the early phase of
      sepsis. In addition, novel experimental approaches, using more clinically
      relevant animal models, to standardize and stratify research outcomes are now
      being argued for. In the present review, we discuss the most recent findings in
      relation to our understanding of the underlying mechanisms involved in septic
      shock, and highlight the attempts made to improve animal experimental models. We
      also review recent studies reporting promising results with two vastly different
      therapeutic approaches influencing the renin-angiotensin system and applying
      mesenchymal stem cells for clinical intervention.

PMID- 24020446
TI  - Renal denervation: current implications and future perspectives.
AB  - SNS (sympathetic nervous system) activation is a common feature of arterial
      hypertension and has been demonstrated to contribute to the development and
      progression of the hypertensive state. Persuasive evidence suggests a strong
      association between SNS overactivity and variety of disease states, including
      chronic renal failure, insulin resistance, congestive heart failure, sleep
      apnoea, ventricular arrhythmias and others. Although sympatholytic agents are
      available to target SNS overactivity pharmacologically, they are not widely used
      in clinical practice, leaving the SNS unopposed in many patients. The recent
      introduction of catheter-based renal denervation as an alternative approach to
      target the SNS therapeutically has been demonstrated to result in a clinically
      relevant blood pressure reduction in patients with resistant hypertension,
      presumably through its effects on both efferent and afferent renal nerve traffic.
      Available data on this interventional procedure demonstrate a favourable vascular
      and renal safety profile. Preliminary data obtained primarily from small and
      mostly uncontrolled studies in related disease states often characterized by
      overactivity of the SNS are promising, but require confirmation in appropriately
      designed clinical trials. In the present paper, we briefly review the physiology
      of the renal nerves and their role in hypertension and other relevant disease
      states, summarize the data currently available from clinical studies pertaining
      to the safety and efficacy of renal denervation in resistant hypertension,
      discuss potential future implications and the available data supporting such a
      role for renal denervation, and describe some of the newer devices currently
      under investigation to achieve improved blood pressure control via renal
      denervation. 

PMID- 24020448
TI  - Reasons for referral, intervention approaches and demographic characteristics of
      clients with intellectual disability attending adult psychiatric outpatient
      services in the Kingdom of Bahrain.
AB  - BACKGROUND: Relatively little information is available regarding the use of
      psychiatric services by individuals with intellectual disability (ID) in Arab
      countries. The current study aimed to identify (1) the reasons for referral; (2)
      demographic characteristics of individuals referred; (3) previous contact with
      child psychiatric services; (4) psychiatric diagnoses; (5) level of ID; (6)
      nature of interventions; and (7) patterns of medication usage in individuals
      attending a specialist psychiatric service for individuals with an ID in the
      Kingdom of Bahrain. METHOD: Case file analysis was used. Files that recorded
      attendance at the specialist service within a specific calendar year were
      selected. A total of 537 files were available for review and 79 contained records
      indicating the individual had been seen within the year. RESULTS: The primary
      referral reason to adult psychiatric services was the presence of behavioural
      disturbance. Pharmacological intervention was the dominant treatment choice and
      no individual was recommended for psychological/behavioural intervention.
      Psychiatric diagnosis was not recorded in over 90% of cases. CONCLUSION: Services
      in the Kingdom of Bahrain for individuals with ID rely exclusively on
      pharmacological approaches for the treatment of behavioural disorders.
      Implications for best practice guidelines are discussed.

PMID- 24020447
TI  - Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic
      dysfunction, and improves survival following experimental sepsis.
AB  - INTRODUCTION: Pharmacological agents that block beta-adrenergic receptors have
      been associated with improved outcome in burn injury. It has been hypothesized
      that injuries leading to a hypermetabolic state, such as septic shock, may also
      benefit from beta-blockade; however, outcome data in experimental models have
      been contradictory. Thus, we investigated the effect of beta-blockade with
      propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression,
      metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP)
      model of sepsis. METHODS: Sprague-Dawley rats receiving either repeated doses (30
      minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or
      control (normal saline), underwent CLP and were monitored for survival.
      Additionally, lung and blood samples were collected at 6 and 24 hours for
      analysis. Animals also underwent monitoring to evaluate global hemodynamics.
      RESULTS: Seven days following CLP, propranolol improved survival versus control
      (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23%
      lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial
      blood pressure was not different between groups. Metabolic analysis of lung
      tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a
      decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids
      (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor
      alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and
      plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a
      significant increase in lung hemeoxygenase-1 expression, a key cellular
      protective heat shock protein (HSP) in the lung. Other lung HSP expression was
      unchanged. CONCLUSIONS: These results suggest that propranolol treatment may
      decrease mortality during sepsis potentially via a combination of improving
      metabolism, suppressing aspects of the inflammatory response and enhancing tissue
      protection.

PMID- 24020449
TI  - Neural activation during response inhibition differentiates blast from mechanical
      causes of mild to moderate traumatic brain injury.
AB  - Military personnel involved in Operations Enduring Freedom and Iraqi Freedom
      (OEF/OIF) commonly experience blast-induced mild to moderate traumatic brain
      injury (TBI). In this study, we used task-activated functional MRI (fMRI) to
      determine if blast-related TBI has a differential impact on brain activation in
      comparison with TBI caused primarily by mechanical forces in civilian settings.
      Four groups participated: (1) blast-related military TBI (milTBI; n=21); (2)
      military controls (milCON; n=22); (3) non-blast civilian TBI (civTBI; n=21); and
      (4) civilian controls (civCON; n=23) with orthopedic injuries. Mild to moderate
      TBI (MTBI) occurred 1 to 6 years before enrollment. Participants completed the
      Stop Signal Task (SST), a measure of inhibitory control, while undergoing fMRI.
      Brain activation was evaluated with 2 (mil, civ)*2 (TBI, CON) analyses of
      variance, corrected for multiple comparisons. During correct inhibitions, fMRI
      activation was lower in the TBI than CON subjects in regions commonly associated
      with inhibitory control and the default mode network. In contrast, inhibitory
      failures showed significant interaction effects in the bilateral inferior
      temporal, left superior temporal, caudate, and cerebellar regions. Specifically,
      the milTBI group demonstrated more activation than the milCON group when failing
      to inhibit; in contrast, the civTBI group exhibited less activation than the
      civCON group. Covariance analyses controlling for the effects of education and
      self-reported psychological symptoms did not alter the brain activation findings.
      These results indicate that the chronic effects of TBI are associated with
      abnormal brain activation during successful response inhibition. During failed
      inhibition, the pattern of activation distinguished military from civilian TBI,
      suggesting that blast-related TBI has a unique effect on brain function that can
      be distinguished from TBI resulting from mechanical forces associated with sports
      or motor vehicle accidents. The implications of these findings for diagnosis and
      treatment of TBI are discussed.

PMID- 24020450
TI  - Extended interactive voice response telephony (IVR) for relapse prevention after
      smoking cessation using varenicline and IVR: a pilot study.
AB  - BACKGROUND: There is a significant resumption of smoking following smoking
      cessation using varenicline. Both smoking cessation medications and counseling
      have been shown to increase smoking quit rates at one year. Thus, the combination
      of varenicline and interactive voice response (IVR) telephony followed by
      extended IVR may further improve smoking cessation rates at one and two years.
      METHODS: 101 participants were recruited from the community via newspaper
      advertisement. They attended a group counseling session and were given smoking
      information booklets from the Canadian Cancer Society. After 12 weeks of
      varenicline and 9 IVR calls, all participants who had quit smoking were
      randomized into 2 groups matched by levels of motivation and addiction as per
      baseline questionnaire score. The intervention group continued to receive bi
      weekly IVR support for weeks 13-52. The control group no longer received IVR. The
      primary end-point was self-reported abstinence and exhaled carbon monoxide levels
      of less than 10 ppm for weeks 12, 52 and 2 years. Data were analyzed by Fisher's
      exact test or Wilcoxon rank-sum test. RESULTS: Of the 101 participants, 44 (43%)
      had stopped smoking after 12 weeks of varenicline and 9 IVR calls. Of these, 23
      (52%) were randomized to receive IVR calls from weeks 13 to 52.At 52 weeks, 26
      (59%) participants remained smoke-free. Of the 23 with IVR, 12 (52.2%) stopped
      smoking compared to 14 of 21 (66.7%) without IVR. At 2 years, 40 of the 44
      (90.9%) randomized participants were contacted and 24 of the 44 (54.5%) came in
      for testing. Fourteen (13% of the original cohort, 30% who were abstinent at 12
      weeks and 53% who were abstinent at 52 weeks) remained smoke-free. Five of the 23
      (21.7%) randomized to IVR and 9 of the 21 (42.9%) randomized to no IVR remained
      smoke-free at 2 years. CONCLUSIONS: In this pilot study of an apparently healthy
      population, extended IVR did not affect abstinence rates. There was no relapse
      prevention benefit in offering 9 months of continued IVR to subjects who had
      stopped smoking after receiving 3 months of varenicline and IVR treatment. TRIAL
      REGISTRATION: ClinicalTrial.gov: NCT00832806.

PMID- 24020451
TI  - A detailed comparative study between chemical and bioactive properties of
      Ganoderma lucidum from different origins.
AB  - A detailed comparative study on chemical and bioactive properties of wild and
      cultivated Ganoderma lucidum from Serbia (GS) and China (GCN) was performed. This
      species was chosen because of its worldwide use as medicinal mushroom. Higher
      amounts of sugars were found in GS, while higher amounts of organic acids were
      recorded in GCN. Unsaturated fatty acids predominated over saturated fatty acids.
      GCN revealed higher antioxidant activity, while GS exhibited inhibitory potential
      against human breast and cervical carcinoma cell lines. No cytotoxicity in non
      tumour liver primary cell culture was observed for the different samples. Both
      samples possessed antibacterial and antifungal activities, in some cases even
      better than the standard antimicrobial drugs. This is the first study reporting a
      comparison of chemical compounds and bioactivity of G. lucidum samples from
      different origins.

PMID- 24020452
TI  - Long-term complete remission with belinostat in a patient with chemotherapy
      refractory peripheral T-cell lymphoma.
AB  - Peripheral T/NK-cell lymphomas (PTCL) are rare malignancies with a poor
      prognosis. Due to the lack of randomised studies, standard therapy has not been
      established. First-line treatment with anthracycline-based polychemotherapy
      followed by consolidation with high-dose therapy and autologous stem cell
      transplant in responding patients has demonstrated good feasibility with low
      toxicity in prospective studies and is widely used in eligible patients. In
      relapsed and refractory patients, who are not candidates for transplant
      approaches, therapeutic options are limited and are usually palliative. Several
      new agents are currently under investigation to improve the outcome of PTCL in
      the first line and salvage settings. Belinostat, a histone deacetylase (HDAC)
      inhibitor, has demonstrated broad antineoplastic activity in preclinical studies,
      and promising results in advanced relapsed/refractory lymphomas.Here, we report
      the case of a 73 year old patient with heavily pre-treated refractory PTCL in
      complete remission with belinostat for 39 months. 

PMID- 24020453
TI  - Waiting times in the ambulatory sector--the case of chronically ill patients.
AB  - AIMS: First, the influence of determinants on the waiting times of chronically
      ill patients in the ambulatory sector is investigated. The determinants are
      subdivided into four groups: (1) need, (2) socio-economic factors, (3) health
      system and (4) patient time pressures. Next, the influence of waiting times on
      the annual number of consultations is examined to assess whether the existing
      variation in waiting times influences the frequency of medical examinations. The
      waiting times of chronically ill patients are analysed since regular ambulatory
      care for this patient group could both improve treatment outcomes and lower
      costs. DATA SOURCES: Individual data from the 2010 Representative Survey
      conducted by the National Association of Statutory Health Insurance Physicians
      (KBV) together with regional data from the Federal Office of Construction and
      Regional Planning. STUDY DESIGN: This is a retrospective observational study. The
      dependent variables are waiting times in the ambulatory sector and the number of
      consultations of General Practitioners (GPs) and specialist physicians in the
      year 2010. The explanatory variables of interest are 'need' and 'health system'
      in the first model and 'length of waiting times' in the second. Negative binomial
      models with random effects are used to estimate the incidence rate ratios of
      increased waiting times and number of consultations. Subsequently, the models are
      stratified by urban and rural areas. RESULTS: In the pooled regression the factor
      'privately insured' shortens the waiting time for treatment by a specialist by
      approximately 28% (about 3 days) in comparison with members of the statutory
      health insurance system. The category of insurance has no influence on the number
      of consultations of GPs. In addition, the regression results stratified by urban
      and rural areas show that in urban areas the factor 'privately insured' reduces
      the waiting time for specialists by approximately 35% (about 3.3 days) while in
      rural areas there is no evidence of statistical influence. In neither of the
      models, however, does the waiting time have a documentable effect on the number
      of consultations in the ambulatory sector. CONCLUSIONS: In our random sample,
      characteristics of the health care system have an influence on the waiting time
      for specialists, but the waiting time has no documentable effect on the number of
      consultations in the ambulatory sector. In the present analysis this applies to
      consultations of both GPs and specialists. Nevertheless, it does not rule out the
      possibility that the length of waiting times might influence the treatment
      outcomes of certain patient populations.

PMID- 24020455
TI  - Faith, folie a famille, and mummification: a brief review of the literature and a
      rare case report.
AB  - Folie a deux is a rare clinical syndrome characterized by the transference of
      delusional ideas from one person to one or more other people in close association
      with the primary affected patient. Mummification indicates the preservation of
      the corpse of a person for a variable period of time. A brief review of the
      literature in this field is presented, and an exceptional case is described,
      characterized by the association of both these rare phenomena. The case is an
      example of folie a fammille which developed out of a condition of extreme
      religiousness and seclusion of an entire family. The shared psychosis led to the
      horrible death of some of the family members, while the last surviving member of
      the family lived for more than a year and a half with their mummified remains.
      The Judge commissioned a forensic psychiatry assessment to verify the survivor's
      ability to bear witness. The development of the psychiatric syndrome and its
      consequences are extensively discussed. 

PMID- 24020454
TI  - Nanofiber orientation and surface functionalization modulate human mesenchymal
      stem cell behavior in vitro.
AB  - Electrospun nanofiber meshes have emerged as a new generation of scaffold
      membranes possessing a number of features suitable for tissue regeneration. One
      of these features is the flexibility to modify their structure and composition to
      orchestrate specific cellular responses. In this study, we investigated the
      effects of nanofiber orientation and surface functionalization on human
      mesenchymal stem cell (hMSC) migration and osteogenic differentiation. We used an
      in vitro model to examine hMSC migration into a cell-free zone on nanofiber
      meshes and mitomycin C treatment to assess the contribution of proliferation to
      the observed migration. Poly (epsilon-caprolactone) meshes with oriented
      topography were created by electrospinning aligned nanofibers on a rotating
      mandrel, while randomly oriented controls were collected on a stationary
      collector. Both aligned and random meshes were coated with a triple-helical, type
      I collagen-mimetic peptide, containing the glycine-phenylalanine-hydroxyproline
      glycine-glutamate-arginine (GFOGER) motif. Our results indicate that nanofiber
      GFOGER peptide functionalization and orientation modulate cellular behavior,
      individually, and in combination. GFOGER significantly enhanced the migration,
      proliferation, and osteogenic differentiation of hMSCs on nanofiber meshes.
      Aligned nanofiber meshes displayed increased cell migration along the direction
      of fiber orientation compared to random meshes; however, fiber alignment did not
      influence osteogenic differentiation. Compared to each other, GFOGER coating
      resulted in a higher proliferation-driven cell migration, whereas fiber
      orientation appeared to generate a larger direct migratory effect. This study
      demonstrates that peptide surface modification and topographical cues associated
      with fiber alignment can be used to direct cellular behavior on nanofiber mesh
      scaffolds, which may be exploited for tissue regeneration.

PMID- 24020456
TI  - Role of metal ion in specific recognition of pyrophosphate ion under
      physiological conditions and hydrolysis of the phosphoester linkage by alkaline
      phosphatase.
AB  - Complexes synthesized from Zn(II), Cu(II), and Cd(II), using a dipicolyl amine
      derivative (L), showed unique specificity toward pyrophosphate ion (PPi or P4O7(4
      )) among all other common anionic analytes, including different biologically
      significant phosphate ion (PO4(3-), H2PO4(2-)) or phosphate-ion-based
      nucleotides, such as AMP, ADP, ATP, and CTP. However, the relative affinities of
      PPi toward these three metal complexes were found to vary and follow the order
      K(a)(L.Zn-PPi) > are given in units of (a)(L.Cu-PPi) >= K(a)(L.Cd-PPi).
      Luminescence responses of the receptor L were substantial on binding to Zn(2+)
      and Cd(2+), while relatively a much smaller luminescence response was observed in
      the presence of Cu(2+). Luminescence responses of L.M-PPi (M is Zn(2+), Cd(2+),
      and Cu(2+)) were further modified on binding to the PPi ion. This could be
      utilized for quantitative detection of PPi in physiological condition as well as
      for developing a real time "turn-on" (for L.Zn and L.Cu) and "turn-off" (for
      L.Cd) fluorescence assay for evaluating the enzymatic activity of alkaline
      phosphatase (ALP). Experimental results revealed how the subtle differences in
      the binding affinities between PPi and M in L.M (M is Zn(2+), Cd(2+), and
      Cu(2+)), could influence the cleavage of the phosphoester linkage in PPi by ALP.
      The DFT calculations further revealed that the hydrolytic cleavage of the metal
      ion coordinated phosphoester bond is kinetically faster than that for free PPi
      and thus, rationalized the observed difference in the cleavage of the
      phosphoester bond by an important mammalian enzyme such as ALP in the presence of
      different metal complexes.

PMID- 24020457
TI  - Introduction to reactive intermediates.

PMID- 24020458
TI  - Characterization of a novel maitake (Grifola frondosa) protein that activates
      natural killer and dendritic cells and enhances antitumor immunity in mice.
AB  - Grifola frondosa, also known as maitake, is a culinary mushroom with immune
      enhancing and antitumor effects. Numerous studies have investigated the activity
      of maitake polysaccharide extracts, but studies of maitake proteins are scarce.
      In this study, we purified and characterized a new G. frondosa protein, GFP, from
      maitake fruiting bodies. GFP is a nonglucan heterodimeric 83 kDa protein that
      consists of two 41 kDa subunits. GFP induced interferon-gamma secretion by murine
      splenocytes and natural killer cells and activated the maturation of bone marrow
      derived dendritic cells (BMDCs) via a TLR4-dependent mechanism. GFP-treated BMDCs
      promoted a Th1 response and exhibited significant antitumor activity when
      transferred into tumor-bearing mice. In conclusion, we are the first to reveal
      the critical role of GFP in modulating the immune response and to link the immune
      enhancing effects of maitake to its antitumor activities. 

PMID- 24020459
TI  - Manipulating surface-related ferromagnetism in modulation-doped topological
      insulators.
AB  - A new class of devices based on topological insulators (TI) can be achieved by
      the direct engineering of the time-reversal-symmetry (TRS) protected surface
      states. In the meantime, a variety of interesting phenomena are also expected
      when additional ferromagnetism is introduced to the original topological order.
      In this Letter, we report the magnetic responses from the magnetically modulation
      doped (Bi(z)Sb(1-z))2Te3/Cr(x)(Bi(y)Sb(1-y))2Te3 bilayer films. By electrically
      tuning the Fermi level across the Dirac point, we show that the top TI surface
      carriers can effectively mediate the magnetic impurities and generate robust
      ferromagnetic order. More importantly, such surface magneto-electric effects can
      be either enhanced or suppressed, depending on the magnetic interaction range
      inside the TI heterostructures. The manipulation of surface-related
      ferromagnetism realized in our modulation-doped TI device is important for the
      realization of TRS-breaking topological physics, and it may also lead to new
      applications of TI-based multifunctional heterostructures.

PMID- 24020461
TI  - Characteristic Raman optical activity signatures of protein beta-sheets.
AB  - In this study, we compute and analyze theoretical Raman optical activity spectra
      of large model beta-sheets in order to identify reliable signatures for this
      important secondary structure element. We first review signatures that have
      already been proposed to be indicative of beta-sheets. From these signatures, we
      find that only the couplet in the amide I region can be regarded as a truly
      reliable signature. In addition, we propose a strong negative peak at ~1350 cm(
      1) to be another good signature for parallel as well as antiparallel beta-sheets.
      We study the robustness of these signatures with respect to perturbations induced
      by the amino acid side chains, the overall conformation of the sheet structure,
      and microsolvation. It is found that the latter effects can be very well
      understood and separated employing the concept of localized modes. Finally, we
      investigate whether Raman optical activity is capable of discriminating between
      parallel and antiparallel beta-sheets. The amide III region turns out to be most
      promising for this purpose. 

PMID- 24020460
TI  - A new cervical nerve root avulsion model using a posterior extra-vertebral
      approach in rats.
AB  - BACKGROUND: The nerve root avulsion injury causes decrease of motor neurons in
      the spinal ventral horn. To investigate the motoneuron death after avulsion
      injury in rats, the intradural root avulsion procedure is usually used, although
      it is technically demanding and associated with a risk of unexpected spinal cord
      damage. We have developed a new cervical nerve root avulsion procedure in rats
      and investigated the validity of our procedure. METHODS: Our procedure is using a
      posterior approach and pulling the C6 nerve root outside the vertebral foramen
      without intradural procedures. The lateral third of the lateral mass is needed to
      be resected before pulling the nerve root. The accomplishment of our procedure is
      judged by confirmation of the bifurcated stump of the avulsed nerve root and the
      leakage of the spinal fluid from vertebral foramen. At first, four Sprague-Dawley
      (SD) rats were used for the examination of C6 motor neuron distribution in the
      normal spinal cord. Then, 40 SD rats were divided into following four groups and
      the survival rate of motor neuron was examined. (A) an intradural avulsion group,
      (B) an intradural rhizotomy group, (C) our extravertebral avulsion group, and (D)
      an extravertebral rupture group. Another 26 SD rats were used for the examination
      of histomorphorogic changes in the spinal cord after our extra-vertebral avulsion
      procedure. RESULTS: At 28 days after injury, the percentage of surviving motor
      neurons in groups A (39.0 +/- 2.1%) and C (47.5 +/- 7.1%) were significantly
      lower than those in groups B (77.1 +/- 12.3%) and D (98.9 +/- 9.9%). Compared
      with other groups, our procedure was easier and associated with less unexpected
      spinal cord damage. Although the length of the distal stump of the
      extravertebrally avulsed ventral rootlets was varied between 1.5 and 3.2 mm, this
      difference did not affect motoneuron death. The extravertebral avulsion injury
      showed intraspinal bleeding along the motoneuron axons, glial reaction and
      macrophage infiltration in the lesioned side of the ventral horn. CONCLUSIONS:
      Our extravertebral avulsion procedure is simple and reproducible. It would become
      a useful tool for the study of cervical nerve root avulsion injury.

PMID- 24020462
TI  - On ethics, the pursuit of knowledge, truth and status in the hallowed halls of
      academe.
AB  - Advancement in academe is largely on the basis of research output; that is,
      refereed journal papers. This paper first explores pressures on academics,
      especially emerging researchers, when English is not a first language. We assess
      why, when faculty members rush to improve their station that they may elect to
      circumvent ethical protocols to accelerate their promotion and status. The
      resulting unethical behavior includes plagiarism and forms of duplication such as
      co-submission. Consideration is then given to the wider implications of both
      plagiarism and the theft of intellectual property, and the role these have played
      in the development of individuals, the university and society. 

PMID- 24020463
TI  - Optimizing the size of the area surveyed for monitoring a Eurasian lynx (Lynx
      lynx) population in the Swiss Alps by means of photographic capture-recapture.
AB  - We studied the influence of surveyed area size on density estimates by means of
      camera-trapping in a low-density felid population (1-2 individuals/100 km(2) ).
      We applied non-spatial capture-recapture (CR) and spatial CR (SCR) models for
      Eurasian lynx during winter 2005/2006 in the northwestern Swiss Alps by sampling
      an area divided into 5 nested plots ranging from 65 to 760 km(2) . CR model
      density estimates (95% CI) for models M0 and Mh decreased from 2.61 (1.55-3.68)
      and 3.6 (1.62-5.57) independent lynx/100 km(2) , respectively, in the smallest to
      1.20 (1.04-1.35) and 1.26 (0.89-1.63) independent lynx/100 km(2) , respectively,
      in the largest area surveyed. SCR model density estimates also decreased with
      increasing sampling area but not significantly. High individual range overlaps in
      relatively small areas (the edge effect) is the most plausible reason for this
      positive bias in the CR models. Our results confirm that SCR models are much more
      robust to changes in trap array size than CR models, thus avoiding overestimation
      of density in smaller areas. However, when a study is concerned with monitoring
      population changes, large spatial efforts (area surveyed >=760 km(2) ) are
      required to obtain reliable and precise density estimates with these population
      densities and recapture rates. 

PMID- 24020464
TI  - Do methods for predicting paleohabitats apply for mountain and insular fossil
      bovids?
AB  - A variety of methods have been developed to use bovid postcranial elements in the
      functional morphology approach to paleohabitat prediction. This study represents
      a first attempt at testing morphometric methods based on astragalus and phalanges
      on extant mountain-dwelling bovids and insular fossil bovids from Sardinia
      assigned to the so-called 'Nesogoral group', already regarded as close to the
      Caprini tribe. We intended to answer the questions whether a classic four
      habitats model could be successfully applied to extant mountain-dwelling bovids,
      and whether results obtained could support the hypothesis of a radiative
      evolution for the Sardinian bovids. Results obtained, on the one hand,
      highlighted some inadequacies of the method if not applied to African bovids; on
      the other hand, they stressed the difficulties of discriminating habitat
      preferences of Sardinian taxa only based on biometry of astragalus and phalanges.
      Nonetheless, statistical habitat predictions suggest the contemporaneous presence
      in Sardinia of bovids having about the same size, but inhabiting different
      environments, giving support to the hypothesis that Sardinian representatives of
      the genus Nesogoral originated from a still unknown ancestor by an adaptive
      radiation evolutionary process. 

PMID- 24020465
TI  - Potential of triptolide in reproductive management of the house rat, Rattus
      rattus.
AB  - Mature and healthy male house rats, Rattus rattus (n= 160) were fed on bait
      (cracked wheat: powdered sugar, 98:2) containing different concentrations of
      triptolide (0.1, 0.05, 0.025 and 0%) for 7 and 14 days in no-choice and bi-choice
      feeding tests in the laboratory. The objective of the study was to record the
      antifertility affects of triptolide after 30 and 60 days of termination of
      treatment. Results revealed no significant effect of triptolide treatment on
      weights of testis, epididymis, seminal vesicles and prostate gland of rats.
      Overall, sperm motility, live sperm count, sperm density and sperm morphology in
      the cauda epididymal fluid were found to differ significantly (P<= 0.05) between
      untreated and treated groups of rats. The major effect of triptolide on sperm
      morphology was in the form of sperm head tail separation, which was up to 56.0%
      in rats treated for 14 days in no-choice and autopsied after 30 days. A
      significant effect (P<= 0.05) of triptolide treatment was observed on the
      histomorphology of the testis, which included a dose-dependent decrease in
      diameter of seminiferous tubules, thickness of germinal epithelium and numbers of
      various spermatogenic cells. Cell associations in the seminiferous epithelial
      cycle were poorly developed in rats ingesting medium (4.7-5.1 mg/100 g bw) and
      high doses (6.9-7.2 mg/100 g bw) of triptolide than rats ingesting low doses (1.8
      2.3 mg/100 g bw) and untreated rats. The cell stages affected had not recovered
      fully within the 60 day period following triptolide withdrawal. The present study
      suggests the potential of triptolide in reproductive management of Rattus rattus.

PMID- 24020466
TI  - Effects of levonorgestrel-quinestrol (EP-1) treatment on Mongolian gerbil wild
      populations: a case study.
AB  - Rodent pest population outbreaks occur frequently in grassland ecosystems in
      northern China. The Mongolian gerbil (Meriones unguiculatus) is a dominant pest
      rodent which is distributed across the semi-desert grasslands of Inner Mongolia,
      China. In 2009, we studied the contraceptive effect of levonorgestrel-quinestrol
      (EP-1), concentration 50 ppm, on a wild Mongolian gerbil population. The one-off
      contraceptive treatment was compared with a control group using a semi-monthly
      live trapping method in the Ordos Semi-desert Grassland Region of Inner Mongolia.
      The results show that juveniles were not recruited in spring in the treatment
      group. Ratios of juveniles in the control and treatment groups showed significant
      semi-monthly differences from spring to summer (one-way ANOVA, F2, 14 = 7.53, P <
      0.05). Between both groups, annual fluctuations of juvenile and total population
      densities were significantly different respectively (F2, 14 = 4.64, P < 0.05; F2,
      18 = 7.72, P < 0.05). The contraceptive EP-1 delayed the normal reproductive
      pattern of Mongolian gerbil populations. This suppressed birth rates of gerbil
      populations, reduced their densities, and changed their age structures. The
      period of EP-1 baiting should be extended but it could be an ideal method for
      controlling Mongolian gerbil populations during each breeding season. 

PMID- 24020467
TI  - Field evaluation of some bait additives against Indian crested porcupine (Hystrix
      indica) (Rodentia: Hystricidae).
AB  - This research study evaluated the effect of different additives on the bait
      consumption by Indian crested porcupine, a serious forest and agricultural pest,
      under field conditions. Different additives (saccharin, common salt, bone meal,
      fish meal, peanut butter, egg yolk, egg shell powder, yeast powder, mineral oil
      and coconut oil) at 2 and 5% each were tested for their relative preference,
      using groundnut-maize (1:1) as basic bait. All the additives were tested under a
      no-choice test pattern. For control tests, no additive was mixed with the basic
      bait. Saccharin at 5% concentration significantly enhanced the consumption of
      bait over the basic bait, while 2% saccharin supplemented bait resulted in a non
      significant bait consumption. All other additives did not enhance the consumption
      of the bait material; rather, these worked as repellents. However, the repellency
      was lowest with the common salt, followed by egg yolk, egg shell powder, bone
      meal, peanut butter, mineral oil, fish meal and yeast powder, while coconut
      remained the most repellent compound. The present study suggested that groundnut
      maize (1:1) supplemented with 5% saccharin was the preferred bait combination,
      and can be used with different rodenticides for the management of Indian crested
      porcupine. 

PMID- 24020468
TI  - Movements and diving behavior of internesting green turtles along Pacific Costa
      Rica.
AB  - Using satellite transmitters, we determined the internesting movements, spatial
      ecology and diving behavior of East Pacific green turtles (Chelonia mydas)
      nesting on Nombre de Jesus and Zapotillal beaches along the Pacific coast of
      northwestern Costa Rica. Kernel density analysis indicated that turtles spent
      most of their time in a particularly small area in the vicinity of the nesting
      beaches (50% utilization distribution was an area of 3 km(2) ). Minimum daily
      distance traveled during a 12 day internesting period was 4.6 +/- 3.5 km. Dives
      were short and primarily occupied the upper 10 m of the water column. Turtles
      spent most of their time resting at the surface and conducting U-dives (ranging
      from 60 to 81% of the total tracking time involved in those activities). Turtles
      showed a strong diel pattern, U-dives mainly took place during the day and
      turtles spent a large amount of time resting at the surface at night. The lack of
      long-distance movements demonstrated that this area was heavily utilized by
      turtles during the nesting season and, therefore, was a crucial location for
      conservation of this highly endangered green turtle population. The unique
      behavior of these turtles in resting at the surface at night might make them
      particularly vulnerable to fishing activities near the nesting beaches. 

PMID- 24020469
TI  - Burrow morphology of Uca uruguayensis and Uca leptodactylus (Decapoda:
      Ocypodidae) from a subtropical mangrove forest in the western Atlantic.
AB  - The continuous excavation of burrows by fiddler crabs generates bioturbation in
      the sediment, which can be estimated from burrow morphology. The aim of the
      present study was to describe the burrow morphology of Uca uruguayensis and U.
      leptodactylus and its relationship with demography of resident individuals and to
      estimate the level of bioturbation in the sediment generated by each species. For
      all individuals from each of the 2 species, sex was determined and the carapace
      width (CW; mm) measured. Burrows were characterized according to burrow diameter
      (BD; mm), maximum burrow depth (MBD; mm) and burrow volume (BV; cm(3) ). The
      density of each species in the study area was also evaluated. In both species,
      the males were larger and occupied burrows with higher BV compared to females.
      Differences between sexes in relation to the burrow characteristics might reflect
      sexual dimorphism within the group and are probably related to the fact that
      males use the burrows for mating. BD and BV showed significant positive
      relationships with the size of resident crabs. The amount of sediment removed per
      burrow was estimated from mean BV: 10.78 cm(3) of sediment/burrow for U.
      uruguayensis and 12.38 cm(3) of sediment/burrow for U. leptodactylus. Despite the
      density and depth differences between the 2 species, the similarity in burrow
      volume suggests that U. uruguayensis and U. leptodactylus present the same
      importance in terms of the bioturbation process. Burrow morphology is highly
      associated with characteristics of the occupant, although extrinsic factors
      should also be considered, and its description can provide estimates on the
      bioturbation generated by Uca species in mangrove forests. 

PMID- 24020470
TI  - Body size variation of four latitudinally-separated populations of a toad
      species: age and growth rate as the proximate determinants.
AB  - Age and growth rate are critical parameters determining the body size of adult
      anurans, which grow indeterminately. Therefore, evaluating their relative
      importance and selective pressures acting on them may help to explain variation
      in body size of anurans across geographical populations. Based on the data on
      body size and skeletochronological age of 4 Asiatic toad (Bufo gargarizans)
      populations that are widely separated in latitude, the present study showed that
      toads at the northern extremity of the range were the oldest, on average, and
      grew relatively fast, toads at the southern end of the range were relatively old
      but grew fastest, whereas mid-latitude toads were intermediate in both traits.
      These results indicated that relative contributions of age and growth rate to
      body size differed among populations. From a life history perspective, greater
      age attained by toads at higher latitudes should result from delayed maturation,
      and faster growth from an adaptive response to strong seasonal time constraints;
      in contrast, selective pressures on the 2 parameters at lower latitudes might be
      associated, respectively, with low adult death rates and longer favorable growing
      seasons. 

PMID- 24020471
TI  - A short note on how tied fights affect cortisol levels.
AB  - Previous work exploring the interrelationships between sex steroids (e.g.
      androgens, testosterones and 11-ketotestosterones) and social behavior in
      teleosts suggest that mirror-elicited aggression in cichlid fish may not trigger
      a hormonal response. Using the Mozambique tilapia (Oreochromis mossambicus) to
      analyze immune responses as a result of social stress, we measured levels of
      cortisol and melatonin using Enzyme-Linked Immunosorbent Assay (ELISA) assays. In
      this work, we demonstrated that cortisol concentrations are significantly lower
      yet the levels of melatonin remain unchanged in tilapia that are fighting their
      mirror image. Our results suggested that in tied fights, certain hormone levels
      remain unchanged (e.g. androgens) due to the lack of melatonin induction. 

PMID- 24020472
TI  - National survey of the prevalence of swallowing difficulty and tube feeding use
      as well as implementation of swallowing evaluation in long-term care settings in
      Japan.
AB  - AIM: The present study was carried out to clarify tube feeding utilization and
      the prevalence of swallowing difficulty among residents in geriatric long-term
      settings, and to elucidate the implementation of swallowing assessment at four
      different types of facilities in Japan. METHODS: We mailed a questionnaire to a
      total of 4334 facilities. RESULTS: We received responses from 1137 (26.2%)
      facilities, including 440 (29.0%) from 1517 nursing homes, 275 (29.2%) from 941
      long-term care facilities, 205 (18.1%) from 1134 sanatorium medical facilities
      and 217 (29.2%) from 742 rehabilitation hospitals. The number of tube-fed
      residents per 100 beds in each facility was 11.6 at the nursing homes, 7.4 at the
      long-term care facilities, 36.3 at the sanatorium medical facilities and 7.9 at
      the rehabilitation facilities. The number of residents per 100 beds with
      swallowing difficulty was 23.7 in the nursing homes, 15.6 in the long-term care
      facilities, 19.2 in the sanatorium medical facilities and 15.4 in the
      rehabilitation hospitals. The percentages of facilities that assessed swallowing
      difficulty were 31.8% of the nursing homes, 63.0% of the long-term care
      facilities, 77.9% of the sanatorium medical facilities and 91.7% of the
      rehabilitation hospitals. CONCLUSION: A large number of residents using a feeding
      tube and with difficult swallowing were observed in geriatric long-term settings
      without adequate evaluation of swallowing function.

PMID- 24020473
TI  - Tetracycline accelerates the temporally-regulated invasion response in specific
      isolates of multidrug-resistant Salmonella enterica serovar Typhimurium.
AB  - BACKGROUND: Multidrug-resistant (MDR) Salmonella isolates are associated with
      increased morbidity compared to antibiotic-sensitive strains and are an important
      health and safety concern in both humans and animals. Salmonella enterica serovar
      Typhimurium is a prevalent cause of foodborne disease, and a considerable number
      of S. Typhimurium isolates from humans and livestock are resistant to three or
      more antibiotics. The majority of these MDR S. Typhimurium isolates are resistant
      to tetracycline, a commonly used and clinically and agriculturally relevant
      antibiotic. Because exposure of drug-resistant bacteria to antibiotics can affect
      cellular processes associated with virulence, such as invasion, we investigated
      the effect tetracycline had on the invasiveness of tetracycline-resistant MDR S.
      Typhimurium isolates. RESULTS: The isolates selected and tested were from two
      common definitive phage types of S. Typhimurium, DT104 and DT193, and were
      resistant to tetracycline and at least three other antibiotics. Although
      Salmonella invasiveness is temporally regulated and normally occurs during late
      log growth phase, tetracycline exposure induced the full invasive phenotype in a
      cell culture assay during early-log growth in several DT193 isolates. No changes
      in invasiveness due to tetracycline exposure occurred in the DT104 isolates
      during early-log growth or in any of the isolates during late-log growth. Real
      time PCR was used to test expression of the virulence genes hilA, prgH, and invF,
      and these genes were significantly up-regulated during early-log growth in most
      isolates due to tetracycline exposure; however, increased virulence gene
      expression did not always correspond with increased invasion, and therefore was
      not an accurate indicator of elevated invasiveness. This is the first report to
      assess DT193 isolates, as well as the early-log growth phase, in response to
      tetracycline exposure, and it was the combination of both parameters that was
      necessary to observe the induced invasion phenotype. CONCLUSIONS: In this report,
      we demonstrate that the invasiveness of MDR S. Typhimurium can be modulated in
      the presence of tetracycline, and this effect is dependent on growth phase,
      antibiotic concentration, and strain background. Identifying the conditions
      necessary to establish an invasive phenotype is important to elucidate the
      underlying factors associated with increased virulence of MDR Salmonella.

PMID- 24020474
TI  - Happy 20th birthday to the Cochrane Collaboration.

PMID- 24020475
TI  - Leadership, accountability, and patient safety.

PMID- 24020476
TI  - An integrative review of skin breakdown in the preterm infant associated with
      nasal continuous positive airway pressure.
AB  - OBJECTIVE: To identify factors associated with skin injury during nasal
      continuous positive airway pressure (NCPAP) and describe differences in
      frequency, severity, and type of skin injuries when comparing nasal interfaces
      used during NCPAP in the preterm infant. DATA SOURCES: Scientific databases were
      searched using provided key terms and yielded 113 articles. STUDY SELECTION:
      Forty-six articles were included in this integrative review: six case studies, 22
      with identified aim of examining skin and nasal injury during NCPAP; 18 included
      skin care considerations during NCPAP. DATA EXTRACTION: Studies were categorized
      into four themes: types of nasal injuries; associated risk factors that increase
      incidence of injury; differences between NCPAP devices and/or nasal interface and
      corresponding rate and severity of nasal injury; and recommended prevention
      strategies to reduce iatrogenic cutaneous injury. DATA SYNTHESIS: Skin injury was
      a common theme during neonatal NCPAP with skin breakdown rates of 20% to 60%.
      Increased skin injury risk was associated with smaller infant size, gestational
      age, and duration of therapy. Nursing care strategies to improve skin integrity
      during NCPAP had little supportive evidence. Nursing practice is varied with
      reportedly little standardized care during NCPAP therapy. Recommendations for
      specific care strategies to reduce skin injury during NCPAP were supported by
      limited experimental studies. CONCLUSIONS: Risk factors during NCPAP include
      nasal injury and trauma secondary to tight-fitting nasal interfaces necessary to
      provide continuous distending pressure for respiratory stability. Identifying
      strategies to reduce skin breakdown will support noninvasive treatment success,
      reduce reintubation rates, reduce sepsis, reduce patient discomfort, and improve
      developmental outcomes during NCPAP use.

PMID- 24020477
TI  - Breastfeeding promotion for management of neonatal abstinence syndrome.
AB  - OBJECTIVE: To review the literature about the association between breastfeeding
      and neonatal abstinence syndrome (NAS) severity, need for pharmacologic treatment
      for NAS, and length of hospital stays in neonates with in-utero exposure to
      methadone or buprenorphine opioid replacement therapy. DATA SOURCES: PubMed,
      CINAHL, and Medline were searched for articles published between January 1990 and
      April 2013 using the terms opioid dependency in pregnancy, neonatal abstinence
      syndrome, methadone, buprenorphine, neonatal length of stay, breastfeeding,
      methadone in breast milk, buprenorphine in breast milk, swaddling, and rooming
      in. STUDY SELECTION: Inclusion criteria included studies written in English on
      the topic of breastfeeding for management of NAS. DATA EXTRACTION: The author
      independently reviewed each article. DATA SYNTHESIS: Breastfeeding can
      effectively decrease NAS symptoms because methadone and buprenorphine are
      transferred to the breast milk. Maternal contact while breastfeeding also plays a
      role in ameliorating the NAS symptoms. Interventions that also support
      breastfeeding in the treatment of NAS include skin-to-skin contact, swaddling,
      and rooming-in. CONCLUSIONS: Understanding the benefits of breastfeeding for
      opioid-dependent pregnant women and their neonates will enable clinicians to
      safely recommend breastfeeding for long-term health of these high-risk women and
      their infants. This review of the effects of in-utero exposure to opioids on
      infant development can assist clinicians to more effectively support opioid
      dependent women to breastfeed their infants.

PMID- 24020478
TI  - Influenza infection control practices in labor and delivery units during the 2009
      H1N1 influenza pandemic.
AB  - OBJECTIVE: To assess the presence and usefulness of written policies and
      practices on infection control consistent with the Center for Disease Control and
      Prevention's (CDC) guidance in hospital labor and delivery (L&D) units during the
      2009 H1N1 influenza pandemic. SETTING: Online survey. PARTICIPANTS: Of 11,845
      eligible nurses, 2,641 (22%) participated. This analysis includes a subset of
      1,866 nurses who worked exclusively in L&D units. METHODS: A cross-sectional
      descriptive evaluation was sent to 12,612 members from the Association of Women's
      Health, Obstetric, and Neonatal Nurses (AWHONN) who reported working in labor,
      delivery, postpartum, or newborn care settings during the 2009 H1N1 influenza
      pandemic. RESULTS: Respondents (73.8%) reported that CDC guidance was very useful
      for infection control in L&D settings during the pandemic. We assessed the
      presence of the following infection control written policies, consistent with
      CDC's guidance in hospital L&D units, during the 2009 H1N1 influenza pandemic and
      their rate of implementation most of the time: questioning women upon arrival
      about recent flu-like symptoms (89.4%, 89.9%), immediate initiation of antiviral
      medicines if flu suspected or confirmed (65.2%, 49%), isolating ill women from
      healthy women immediately (90.7%, 84.7%), ask ill women to wear masks during L&D
      (67%, 57.7%), immediately separating healthy newborns from ill mothers (50.9%,
      42.4%), and bathing healthy infants when stable (58.4%, 56.9%). Reported written
      policies for five of the six practices increased during the pandemic. Five of six
      written policies remained above baseline after the pandemic. CONCLUSIONS:
      Respondents considered CDC guidance very useful. The presence of written policies
      is important for the implementation of infection control practices by L&D nurses.

PMID- 24020479
TI  - Angiotensinogen promoter and angiotensinogen II receptor type 1 gene
      polymorphisms and incidence of ischemic stroke and neurologic phenotype in Fabry
      disease.
AB  - CONTEXT: Stroke and/or white matter lesions (WMLs) are significant in Fabry
      disease. Polymorphisms of angiotensinogen (AGT), AGT Promoter and angiotensinogen
      II receptor type 1 (AGTR1) are correlated with WMLs. OBJECTIVES: We compared AGT.
      AGT Promoter and AGTR1 genotypes to stroke incidence, Fabry-specific [Mainz
      Severity Score Index (MSSI)] severity score, and neurologic sub-score (n-MSSI).
      METHODS: Sixty-three Fabry patients and 49 matched controls plus historic
      controls were genotyped. Institutional Review Board approval was received.
      Results. C and/or CC alleles of AGT Promoter and AGTR1 were significantly
      correlated with stroke and n-MSSI. DISCUSSION/CONCLUSION: Findings are suggestive
      of role of AGT Promoter and AGTR1 genotypes in Fabry phenotypes.

PMID- 24020480
TI  - A high incidence of exanthematous eruption associated with niacin/laropiprant
      combination in Hong Kong Chinese patients.
AB  - WHAT IS KNOWN AND OBJECTIVE: Niacin commonly causes cutaneous flushing, which is
      partially alleviated by laropiprant, a selective antagonist of prostaglandin D2
      at the DP1 receptor. Here we report an unusually high incidence of exanthematous
      eruption associated with the use of the extended-release (ER) niacin/laropiprant
      combination treatment in Hong Kong Chinese patients. CASE DESCRIPTION: Among 201
      patients treated with ER niacin/laropiprant 1000/20 mg over 7 days to assess
      flushing symptoms and 166 of the patients who continued the treatment for 12
      weeks (doubling the dose after 4 weeks), 28 patients (14%) developed a highly
      pruritic cutaneous eruption at a mean of 5 days after starting the treatment or 4
      days after increasing the dose. This resolved over several days after drug
      withdrawal with symptomatic treatment. Compared with the subjects who completed
      12-weeks treatment uneventfully, those who developed cutaneous eruption were
      older, had significantly lower body weight, were taking background lipid-lowering
      treatment more frequently and had greater flushing responses in the first few
      days of treatment. WHAT IS NEW AND CONCLUSION: The relationship of the
      exanthematous eruption with lower body weight and the increase in dosage suggests
      a pharmacokinetic effect that may be related to increased exposure to niacin or
      its metabolites and provoked by inhibition of the DP1 receptor with laropiprant,
      as we have not seen this rash with niacin used alone. This may suggest that the
      southern Chinese population may have some genetic predisposition; as such, a high
      frequency of exanthematous reactions has not been reported in other populations.

PMID- 24020485
TI  - Compartment syndrome diagnosed in due time by breakthrough pain despite
      continuous peripheral nerve block.
AB  - We here present a paediatric case with development of acute compartment syndrome
      in the lower leg secondary to a tibial shaft fracture. The patient was diagnosed
      in time because of breakthrough pain, despite a well-functioning continuous
      peripheral nerve block with ropivacaine infusion. Compartment syndrome is a
      potentially devastating complication to trauma, typically fractures of the tibial
      shaft and the forearm because of the relatively tight facias and small volume of
      these compartments. 

PMID- 24020486
TI  - Comprehensive evaluation of differential gene  expression analysis methods for
      RNA-seq data.
AB  - A large number of computational methods have been developed for analyzing
      differential gene expression in RNA-seq data. We describe a comprehensive
      evaluation of common methods using the SEQC benchmark dataset and ENCODE data. We
      consider a number of key features, including normalization, accuracy of
      differential expression detection and differential expression analysis when one
      condition has no detectable expression. We find significant differences among the
      methods, but note that array-based methods adapted to RNA-seq data perform
      comparably to methods designed for RNA-seq. Our results demonstrate that
      increasing the number of replicate samples significantly improves detection power
      over increased sequencing depth.

PMID- 24020487
TI  - Mindfulness-based cognitive therapy for adults with intellectual disabilities: an
      evaluation of the effectiveness of mindfulness in reducing symptoms of depression
      and anxiety.
AB  - BACKGROUND: Mindfulness-based interventions have been shown to be effective in
      the treatment of a range of health and psychological disorders in adults and
      young people without intellectual disabilities (ID). Clinical studies are
      emerging reporting on the efficacy of mindfulness-based interventions as a stand
      alone treatment for common clinical disorders in adults with ID. METHOD: This
      paper aims to evaluate the efficacy of an innovative structured mindfulness-based
      cognitive therapy (MBCT) group programme adapted for adults with ID with a
      diagnosis of either recurrent depression, anxiety or both clinical conditions and
      a history of deliberate self-harm behaviour. Two groups ran consecutively
      consisting of a total of fifteen participants and seven carers. All participants
      were recorded as having either a borderline, mild, or moderate ID. The group
      programme ran over a period of 9 weeks with a follow-up session at 6 weeks post
      group intervention. Outcome measures included the Hospital Anxiety and Depression
      Scale and two sub-scales from the Self-Compassion Scale administered at baseline,
      post therapy and at 6-week follow-up. RESULTS: The evaluation showed that
      participants reported an improvement in their experience of depression, anxiety,
      self-compassion and compassion for others. The most significant impact was in the
      reduced levels of anxiety reported. Improvements across all outcomes were
      maintained at 6-week follow-up. CONCLUSION: The results of the evaluation suggest
      that people with intellectual disabilities benefit from a structured MBCT group
      intervention and the results are maintained at 6-week follow-up.

PMID- 24020488
TI  - Expression and promoter methylation changes of the P15INK4b during ex vivo cord
      blood CD34+ cell expansion following co-culture with mesenchymal stromal cells.
AB  - BACKGROUND: Because of the insufficient number of cord blood hematopoietic stem
      cells (CB-HSC), expansion of these cells seems to be important for clinical
      application in adults. Cell cycle inhibitors are important regulators in normal
      hematopoietic regeneration. In this study, mRNA expression and promoter
      methylation status of p15(INK4b) were evaluated during CB-HSC ex vivo expansion
      using cytokines and in co-culture system with a mesenchymal stem cells (MSCs)
      feeder layer. METHODS: ex vivo cultures of CB-HSCs were performed in three
      culture conditions for 14 days: cytokines with an MSCs feeder layer, cytokines
      without a MSCs feeder layer, and co-culture with MSCs without cytokines. After
      expansion, measuring the total number of cells, CD34(+) cells, and CFU assay was
      performed. Methylation status of the p15(INK4b) gene promoter was analyzed using
      methylation-specific polymerase chain reaction and p15 mRNA expression was
      evaluated by real-time reverse transcriptase polymerase chain reaction. RESULTS:
      Maximum CB-HSC expansion was observed on day 10 of expansion. The data showed
      that after 10 days, p15 mRNA expression in the expanded cells in all the three
      culture conditions was higher than in CD34(+) fresh cells (P < 0.01). p15 gene
      promoter of expanded CD34(+) cells remained in an unmethylated form just like
      fresh CD34(+) cells in all the three culture conditions at days 5, 10, and 14 of
      culture. CONCLUSIONS: Expression of p15(INK4b) in HSCs was not decreased during
      ex vivo expansion. Also, no methylation of p15 promoter was observed, otherwise
      it would be capable of initiating some leukemic cell progression or disruption in
      hematopoietic regeneration.

PMID- 24020489
TI  - Iron deficiency anemia.

PMID- 24020490
TI  - Myelodysplasia.

PMID- 24020491
TI  - Assessment of sexual violence among street females in Bahir-Dar town, North West
      Ethiopia: a mixed method study.
AB  - BACKGROUND: Sexual violence is a major public health concern as well as human
      rights violation. Homeless women are far more likely to experience violence of
      all sorts than women in general. The objective of this study is to assess the
      prevalence and consequence of rape, and explore the reasons and factors
      associated with rape among street females in Bahir-Dar town, North West Ethiopia.
      METHODS: This is a mixed method study which included: a survey of 395 street
      females age 15-49; key informant interview with 4 stakeholders; 5 case studies;
      one focus group of 10 street females and one focus group of 10 street males.
      Street females are those who spend most of their time on the street and who
      depend on the street for their life. Qualitative and quantitative data were
      assessed separately with thematic and statistical analysis respectively.
      Quantitative data was analyzed using SPSS version 16.0. Bivariate and
      Multivariate analysis were determined. RESULTS: Life time prevalence of rape was
      24.3% and the prevalence of rape in the last year was 11.4%. Factors like females
      "off" the street [OR (95% CI) =6.2 (3.0, 12.9)], being a prostitute [OR (95% CI)
      = 4.1 (1.5, 11.1)] and age 15-29 [OR (95% CI) =3.5 (1.1, 11.2)] were
      significantly associated with rape. Most, 93.8% of the rapes were not reported to
      legal bodies. None of the victims used condom during the rape event. Only, 4
      (4.2%) of the victims used emergency contraceptive method following the rape
      event. Out of the total of 96 victims of rape, 13 (19.1%) and 9 (13.2%)
      experienced unwanted pregnancy and induced abortion respectively. Beside, 38
      (41%) and 15 (22%) victims claimed genital injury and unusual vaginal discharge
      respectively. Psychological consequence like, hating others by 34 (35.8%), fear
      and concern for HIV/AIDS by 44 (46.6%), guilt feeling by 28 (29.4%) and loss of
      interest in sexual activity by 28 (29.4%) of victims were reported. Majority,
      42.9% of victims attribute their victimization with sleeping in areas where there
      are many brothels. Being physically weak, long stay in street life, and sleeping
      around street males were reasons mentioned for rape by 11.9%, 29.7% and 15.4% of
      rape victims respectively. CONCLUSION: In general, there is a very high
      prevalence of rape exacting significant physical and psychological tolls in
      victims of the study. Therefore, timely and integrated actions of the various
      stakeholders working in this area are crucial to curtail this critical human
      rights violation.

PMID- 24020492
TI  - Characteristics of suicide hotspots on the Belgian railway network.
AB  - In 2004, railway suicide accounted for 5.3% of all suicides in Belgium. In 2008,
      Infrabel (Manager of the Belgian Railway Infrastructure) introduced a railway
      suicide prevention programme, including identification of suicide hotspots, i.e.,
      areas of the railway network with an elevated incidence of suicide. The study
      presents an analysis of 43 suicide hotspots based on Infrabel data collected
      during field visits and semi-structured interviews conducted in mental health
      facilities in the vicinity of the hotspots. Three major characteristics of the
      hotspots were accessibility, anonymity, and vicinity of a mental health
      institution. The interviews identified several risk and protective factors for
      railway suicide, including the training of staff, introduction of a suicide
      prevention policy, and the role of the media. In conclusion, a comprehensive
      railway suicide prevention programme should continuously safeguard and monitor
      hotspots, and should be embedded in a comprehensive suicide prevention programme
      in the community. 

PMID- 24020493
TI  - Cause-specific telomere factors deregulation in hepatocellular carcinoma.
AB  - BACKGROUND: Among the numerous genetic defects associated with
      hepatocarcinogenesis, telomere abnormalities appear to play a role both in tumor
      promotion and maintenance. Telomeres, the chromosome extremities, are protected
      by specific proteins, the shelterin complex and by additional factors. Besides
      telomerase dysregulation, expression changes of these telomere factors have been
      observed in cancers. METHODS: Here, we tested the hypothesis that such
      dysregulation might occur in hepatocellular carcinoma (HCC) with specific
      patterns depending on the cause of HCC. We compared telomere length, telomerase
      activity (TA), hTERT and telomere genes expression using PCR and Western-blot
      analyses between non-cirrhotic liver, peritumoral cirrhotic tissue (40 samples)
      and cancerous tissue (40 samples) derived from 40 patients with HBV-, HCV-, or
      alcohol-related HCC. RESULTS: Alterations in TA, hTERT expression and telomere
      length between non-cirrhotic, cirrhotic, and tumor samples were not significantly
      influenced by the cause of HCC. In contrast, the expression pattern of hTR,
      shelterin, and non-shelterin telomere protective factors clearly distinguished
      the 3 causes of cirrhosis and HCC. For patients with HBV diseased liver, when
      compared with non-cirrhotic liver, the cirrhotic tissue underexpressed all
      shelterin and all but HMRE11A and RAD50 non-shelterin telomere factors. For HCV
      the expression level of POT1, RAP1, Ku80, and RAD50 was higher in cirrhotic than
      in non-cirrhotic liver samples without evidence for significant transcriptional
      change for the remaining genes. For alcohol-related liver diseases, the
      expression level of POT1, RAP1, TIN2, hMRE11A, hMRE11B, Ku70, Ku80, RAD50, TANK1,
      and PINX1 was higher in cirrhotic than in non-cirrhotic liver samples. For the 3
      causes of HCC, there was no significant change in shelterin and non-shelterin
      gene expression between cirrhosis and HCC samples. CONCLUSIONS: These results
      validate our hypotheses and demonstrate that cirrhosis and HCC add-up numerous
      telomere dysfunctions including numerous cause-specific changes that appear to
      occur early during the course of the disease.

PMID- 24020494
TI  - State and national household concentrations of PM2.5 from solid cookfuel use:
      results from measurements and modeling in India for estimation of the global
      burden of disease.
AB  - BACKGROUND: Previous global burden of disease (GBD) estimates for household air
      pollution (HAP) from solid cookfuel use were based on categorical indicators of
      exposure. Recent progress in GBD methodologies that use integrated-exposure
      response (IER) curves for combustion particles required the development of models
      to quantitatively estimate average HAP levels experienced by large populations.
      Such models can also serve to inform public health intervention efforts. Thus, we
      developed a model to estimate national household concentrations of PM2.5 from
      solid cookfuel use in India, together with estimates for 29 states. METHODS: We
      monitored 24-hr household concentrations of PM2.5, in 617 rural households from 4
      states in India on a cross-sectional basis between November 2004 and March 2005.
      We then, developed log-linear regression models that predict household
      concentrations as a function of multiple, independent household level variables
      available in national household surveys and generated national / state estimates
      using The Indian National Family and Health Survey (NFHS 2005). RESULTS: The
      measured mean 24-hr concentration of PM2.5 in solid cookfuel using households
      ranged from 163 MUg/m3 (95% CI: 143,183; median 106; IQR: 191) in the living area
      to 609 MUg/m3 (95% CI: 547,671; median: 472; IQR: 734) in the kitchen area. Fuel
      type, kitchen type, ventilation, geographical location and cooking duration were
      found to be significant predictors of PM2.5 concentrations in the household
      model. k-fold cross validation showed a fair degree of correlation (r = 0.56)
      between modeled and measured values. Extrapolation of the household results by
      state to all solid cookfuel-using households in India, covered by NFHS 2005,
      resulted in a modeled estimate of 450 MUg/m3 (95% CI: 318,640) and 113 MUg/m3
      (95% CI: 102,127) , for national average 24-hr PM2.5 concentrations in the
      kitchen and living areas respectively. CONCLUSIONS: The model affords substantial
      improvement over commonly used exposure indicators such as "percent solid
      cookfuel use" in HAP disease burden assessments, by providing some of the first
      estimates of national average HAP levels experienced in India. Model estimates
      also add considerable strength of evidence for framing and implementation of
      intervention efforts at the state and national levels.

PMID- 24020496
TI  - Off-clamp laparoscopic partial nephrectomy for hilar tumors: oncologic and renal
      functional outcomes.
AB  - OBJECTIVES: To present our experience demonstrating the feasibility of off-clamp
      laparoscopic partial nephrectomy (LPN) for hilar tumors and evaluate intermediate
      oncologic and renal functional outcomes. PATIENTS AND METHODS: A retrospective
      review of LPN cases in nine patients was performed. Hilar lesions were defined as
      renal cortical tumors in direct physical contact with the renal artery, vein, or
      both as identified on preoperative imaging and confirmed intraoperatively.
      Although the renal hilum vasculature was isolated for possible clamping if
      needed, tumor extirpation was performed off-clamp, eliminating warm ischemia time
      (WIT). The clinicopathologic parameters, perioperative course, complications, and
      long-term oncologic and renal functional outcomes were analyzed. RESULTS: Nine
      patients underwent off-clamp LPN for complex hilar tumors. The mean age was 60.5
      years, mean American Society of Anesthesiologists physical classification (ASA)
      score was 2, and mean BMI was 27.7 kg/m(2). The mean tumor size and volume were
      3.2 cm and 35.8 cm(3), respectively. A greater proportion of the tumors (55.6%)
      were endophytic and mostly of clear cell histology (78%). The mean operative time
      was 131 minutes, estimated blood loss 250 cc, need for transfusion 0%, and
      complication rates 22%. No positive margins were present intraoperatively or on
      final pathology. After a median follow-up of 42.8 months, there was no evidence
      of clinical or radiographic recurrence in any patient. There was no change in the
      mean estimated glomerular filtration rate preoperatively and at a median follow
      up of 32 months (97.2 mL/minute vs 81.3 mL/minute; p=0.052). CONCLUSION: Complex
      renal hilar tumors can be successfully managed with laparoscopic nephron-sparing
      surgery with elimination of WIT with preservation of perioperative, renal
      functional, and oncologic outcomes.

PMID- 24020495
TI  - Probiotic characterization of potential hydrolases producing Lactococcus lactis
      subsp. lactis isolated from pickled yam.
AB  - The aim of this study was to characterize potential probiotic strain co-producing
      alpha-amylase and beta-galactosidase. Sixty-three strains, isolated from pickle
      samples were screened for their hydrolase producing capacity by utilizing
      different starches as carbon source. One out of 63 strains, isolated from
      traditionally fermented pickled yam showing maximum hydrolase activity (alpha
      amylase (36.9 U/ml) and beta-galactosidase (42.6 U/ml)) within a period of 48
      hours was identified as Lactococcus lactis subsp. lactis. Further, it was
      assessed for the probiotic characteristics under gastrointestinal conditions like
      acidic, alkaline, proteolytic enzymes, bile stress and found to exhibit tolerance
      to these stresses. The therapeutic potential of the isolate is implicated because
      of its antagonistic effect against enteric foodborne pathogens (Salmonella
      typhimurium, Escherichia coli 0157:H7, Staphylococcus aureus, Yersinia
      enterocolitica and Aeromonas hydrophila). The results of this study entail a
      potential applicability of the isolate in developing future probiotic foods
      besides the production of industrially significant hydrolases.

PMID- 24020497
TI  - Poly(glycerol sebacate) elastomer: a novel material for mechanically loaded bone
      regeneration.
AB  - The selection criteria for potential bone engineering scaffolds are based chiefly
      on their relative mechanical comparability to mature bone. In this study, we
      challenge this notion by obtaining full regeneration of a rabbit ulna critical
      size defect by employing the elastomeric polymer, poly(glycerol sebacate) (PGS).
      We tested the regeneration facilitated by PGS alone, PGS in combination with
      hydroxyapatite particles, or PGS seeded with bone marrow stromal cells. We
      investigated the quantity and quality of the regenerated bone histologically, by
      microcomputed tomography and by four-point bending flexural mechanical testing at
      8 weeks postimplantation. We conclude that the relatively lower stiffness of this
      biocompatible elastomer allows a load-transducing milieu in which osteogenesis,
      matrix deposition, and eventual bone maturation can take place. This study's
      results suggest that PGS elastomer is an auspicious osteoconductive material for
      the regeneration of bony defects. These results call for an innovative
      reassessment of the current art of selection for novel bone scaffold materials. 

PMID- 24020498
TI  - MamX encoded by the mamXY operon is involved in control of magnetosome maturation
      in Magnetospirillum gryphiswaldense MSR-1.
AB  - BACKGROUND: Magnetotactic bacteria produce membrane-enveloped magnetite crystals
      (magnetosomes) whose formation is controlled primarily by a gene island termed
      the magnetosome island (MAI). Characterization of single gene and operon function
      in MAI has elucidated in part the genetic basis of magnetosome formation. The
      mamX gene, located in the mamXY operon, is highly conserved in the MAI of all
      Magnetospirillum strains studied to date. Little is known regarding the function
      of mamX in the process of biomineralization. RESULTS: A mamX deletion mutant
      (?mamX) and its complemented strain (CmamX) by conjugation in M. gryphiswaldense
      strain MSR-1 were constructed. There were no striking differences in cell growth
      among ?mamX, CmamX, and wild-type strain (WT). ?mamX displayed a much weaker
      magnetic response than WT. Transmission electron microscopy revealed the presence
      of irregular, superparamagnetic magnetite particles in ?mamX, in contrast to
      regular, single-domain particles in WT and CmamX. The phenotype of ?mamX was
      similar to that of an ftsZ-like deleted mutant and mamXY operon deleted mutant
      reported previously. Quantitative real-time RT-PCR (qPCR) results indicated that
      the deletion of mamX had differential effects on the transcription levels of the
      other three genes in the operon. CONCLUSIONS: The MamX protein plays an important
      role in controlling magnetosome size, maturation, and crystal form. The four
      MamXY proteins appear to have redundant functions involved in magnetosome
      formation. Our findings provide new insights into the coordinated function of MAI
      genes and operons in magnetosome formation.

PMID- 24020499
TI  - Density functional analysis of like-charged attraction between two similarly
      charged cylinder polyelectrolytes.
AB  - A systematic theoretical investigation is performed for electrostatic potential
      of mean force (EPMF) between two similarly charged rods (modeling DNA) immersed
      in a primitive model electrolyte solution. Two scientific anomalies are
      disclosed: (i) although a like-charge attraction (LCA) generally becomes stronger
      with bulk electrolyte concentration, the opposite effect unexpectedly occurs if
      the two rod surfaces involved are sufficiently charged and (2) contrary to what
      is often asserted, that the presence of multivalent counterion is necessary to
      induce the LCA, it is found that the univalent counterion induces the LCA solely
      only if bulk electrolyte concentration rises sufficiently and the rod surface
      charge quantities are high. On the basis of the system energetics calculated
      first by a classical density functional theory in three-dimensional space, a
      hydrogen-bonding style mechanism is advanced to reveal the origin of the LCA, and
      by appealing to fairly common-sense concepts such as bond energy, bond length,
      number of hydrogen bonds formed, and counterion single-layer saturation
      adsorption capacity, the present mechanism successfully explains the scientific
      anomalies and effects of counterion and co-ion diameters in eliciting the LCA
      first investigated in this work. To add weight to the hydrogen-bonding style
      mechanism, a theoretical investigation is further performed regarding the effects
      of the rod surface charge density, co-ion valence, relative permittivity of the
      medium, temperature, nonelectrostatic interion interactions, and rod diameter in
      modifying the EPMF, and several novel phenomena are first confirmed, which is
      self-consistently explained by the present hydrogen-bonding style mechanism. 

PMID- 24020500
TI  - Chiral induction at octahedral Ru(II) via the disassembly of diruthenium(II,III)
      tetracarboxylates using a variety of chiral diphosphine ligands.
AB  - Achiral [Ru2(MU-O2CR)4(MeOH)2](PF6) (R = CH3 or C6H5) reacts with the chiral
      diphosphines R,R- and S,S-Chiraphos (two chiral centers on ligand between the
      coordinating P atoms) and R-Prophos (one chiral center on ligand between the
      coordinating P atoms) leading to a disassembly of the paddlewheel core and the
      highly diastereoselective production of Lambda-[Ru(eta(2)-O2CC6H5)(eta(2)-R,R
      Chiraphos)2](PF6) (Lambda-R,R-III), Delta-[Ru(eta(2)-O2CC6H5)(eta(2)-S,S
      Chiraphos)2](PF6) (Delta-S,S-III) (the R = CH3 complexes of Chiraphos were
      reported in a earlier communication in this journal), and Lambda-[Ru(eta(2)
      O2CCH3)(eta(2)-R-Prophos)2](PF6) (Lambda-R,R-VI), respectively, in high yield and
      purity. Reactions of the same starting material with R,R- and S,S-o-tolyl-Dipamp
      (chiral centers are the coordinating P-atoms) lead to an inversion in the
      chirality-at-metal producing Lambda-[Ru(eta(2)-O2CC6H5)(eta(2)-S,S-o-tolyl
      Dipamp)2](PF6) (Lambda-S,S-IV), Delta-[Ru(eta(2)-O2CC6H5)(eta(2)-R,R-o-tolyl
      Dipamp)2](PF6) (Delta-R,R-IV), Lambda-[Ru(eta(2)-O2CCH3)(eta(2)-S,S-o-tolyl
      Dipamp)2](PF6) (Lambda-S,S-V), and Delta-[Ru(eta(2)-O2CCH3)(eta(2)-R,R-o-tolyl
      Dipamp)2](PF6) (Delta-R,R-V). X-ray crystallography of all but Lambda-S,S-V and
      Delta-R,R-V and solid-state circular dichroism (CD) show that only the indicated
      diastereomers are present in the solid-state. Solution CD measurements and (31)P
      NMR also indicate their predominance in solution. 

PMID- 24020501
TI  - Formation of fused-ring 2'-deoxycytidine adducts from 1-chloro-3-buten-2-one, an
      in vitro 1,3-butadiene metabolite, under in vitro physiological conditions.
AB  - 1-Chloro-3-buten-2-one (CBO) is a potential metabolite of 1,3-butadiene (BD), a
      carcinogenic air pollutant. CBO is a bifunctional alkylating agent that readily
      reacts with glutathione (GSH) to form mono-GSH and di-GSH adducts. Recently, CBO
      and its precursor 1-chloro-2-hydroxy-3-butene (CHB) were found to be cytotoxic
      and genotoxic in human liver cells in culture with CBO being approximately 100
      fold more potent than CHB. In the present study, CBO was shown to react readily
      with 2'-deoxycytidine (dC) under in vitro physiological conditions (pH 7.4, 37 
      degrees C) to form four dC adducts with the CBO moieties forming fused rings with
      the N3 and N(4) atoms of dC. The four products were structurally characterized as
      2-hydroxy-2-hydroxymethyl-7-(2-deoxy-beta-d-erythro-pentofuranosyl)-1,2,3,4
      tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-1 and dC-2, a pair of
      diastereomers), 4-chloromethyl-4-hydroxy-7-(2-deoxy-beta-d-erythro
      pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC
      3), and 2-chloromethyl-2-hydroxy-7-(2-deoxy-beta-d-erythro-pentofuranosyl)
      1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-4).
      Interestingly, dC-1 and dC-2 were stable under our experimental conditions (pH
      7.4, 37  degrees C, and 6 h) and existed in equilibrium as indicated by HPLC
      analysis, whereas dC-3 and dC-4 were labile with the half-lives being 3.0 +/-
      0.36 and 1.7 +/- 0.06 h, respectively. Decomposition of dC-4 produced both dC-1
      and dC-2, whereas acid hydrolysis of dC-1/dC-2 and dC-4 in 1 M HCl at 100 
      degrees C for 30 min yielded the deribosylated adducts dC-1H/dC-2H and dC-4H,
      respectively. Because fused-ring dC adducts of other chemicals are mutagenic, the
      characterized CBO-dC adducts could be mutagenic and play a role in the
      cytotoxicity and genotoxicity of CBO and its precursors, CHB and BD. The CBO-dC
      adducts may also be used as standards to characterize CBO-DNA adducts and to
      develop potential biomarkers for CBO formation in vivo. 

PMID- 24020502
TI  - Sleep and frailty syndrome in elderly residents of long-stay institutions: a
      cross-sectional study.
AB  - AIM: Aging changes sleep patterns in most elderly people. Frailty shares a number
      of characteristics with sleep disorders and leads to similar results. However,
      their relationship in residents of long-stay institutions remains unclear. Thus,
      the present study aimed to evaluate the relationship between sleep and frailty
      syndrome in residents of long-stay institutions. METHODS: This was a cross
      sectional study of 69 institutionalized elderly in the city of Joao Pessoa,
      Brazil. The Pittsburg Sleep Quality Index, actimetry and specific tests for
      frailty phenotype variables were used. Pearson's chi(2)-test, one-way anova and
      multiple linear regression were applied in statistical analysis. RESULTS: The
      sample was characterized as predominantly frail (49.3%), mainly women (62.3%),
      with a mean age of 77.52 years (+/- 7.82). Frail elderly exhibited poor sleep
      quality, when compared with non-frail individuals (P = 0.02). In the multiple
      linear regression analysis, sleep latency (R(2) = 0.11, P = 0.003) and sleep
      quality (R(2) = 0.08, P = 0.013) had an influence on frailty, especially sleep
      quality. No differences were found between rest-activity pattern and frailty
      phenotype. CONCLUSION: Sleep alterations, including poor sleep quality and
      prolonged latency, were related to frailty in institutionalized elderly.

PMID- 24020504
TI  - Essential prerequisites for successful bioprocess development of biological CH4
      production from CO2 and H2.
AB  - The production and storage of energy from renewable resources steadily increases
      in importance. One opportunity is to utilize carbon dioxide (CO2)-type
      hydrogenotrophic methanogens, which are an intriguing group of microorganisms
      from the domain Archaea, for conversion of hydrogen and CO2 to methane (CH4).
      This review summarizes the current state of the art of bioprocess development for
      biological CH4 production (BMP) from pure cultures with pure gasses. The
      prerequisites for successful quantification of BMP by using closed batch, as well
      as fed-batch and chemostat culture cultivation, are presented. This review shows
      that BMP is currently a much underexplored field of bioprocess development, which
      mainly focuses on the application of continuously stirred tank reactors. However,
      some promising alternatives, such as membrane reactors have already been adapted
      for BMP. Moreover, industrial-based scale-up of BMP to pilot scale and larger has
      not been conducted. Most crucial parameters have been found to be those, which
      influence gas-limitation fundamentals, or parameters that contribute to the
      complex effects that arise during medium development for scale-up of BMP
      bioprocesses, highly stressing the importance of holistic BMP quantification by
      the application of well-defined physiological parameters. The much underexplored
      number of different genera, which is mainly limited to Methanothermobacter spp.,
      offers the possibility of additional scientific and bioprocess development
      endeavors for the investigation of BMP. This indicates the large potential for
      future bioprocess development considering the possible application of
      bioprocessing technological aspects for renewable energy storage and power
      generation. 

PMID- 24020505
TI  - Calcium-energized motor protein forisome controls damage in phloem: potential
      applications as biomimetic "smart" material.
AB  - Forisomes are ATP independent, mechanically active proteins from the Fabaceae
      family (also called Leguminosae). These proteins are located in sieve tubes of
      phloem and function to prevent loss of nutrient-rich photoassimilates, upon
      mechanical injury/wounding. Forisomes are SEO (sieve element occlusion) gene
      family proteins that have recently been shown to be involved in wound sealing
      mechanism. Recent findings suggest that forisomes could act as an ideal model to
      study self assembly mechanism for the development of nanotechnological devices
      like microinstruments, the microfluidic system frequently used in space
      exploration missions. Technology enabling improvement in micro instruments has
      been identified as a key technology by NASA in future space exploration missions.
      Forisomes are designated as biomimetic smart materials which are calcium
      energized motor proteins. Since forisomes are biomolecules from plant systems it
      can be doctored through genetic engineering. In contrast, "smart" materials which
      are not derived from plants are difficult to modify in their properties. Current
      levels of understanding about forisomes conformational shifts with respect to
      calcium ions and pH changes requires supplement of future advances with relation
      to its 3D structure to understand self assembly processes. In plant systems it
      forms blood clots in the form of occlusions to prevent nutrient fluid leakage and
      thus proves to be a unique damage control system of phloem tissue. 

PMID- 24020503
TI  - Unfolded protein response in Gaucher disease: from human to Drosophila.
AB  - BACKGROUND: In Gaucher disease (GD), resulting from mutations in the GBA gene,
      mutant beta-glucocerebrosidase (GCase) molecules are recognized as misfolded in
      the endoplasmic reticulum (ER). They are retrotranslocated to the cytoplasm,
      where they are ubiquitinated and undergo proteasomal degradation in a process
      known as the ER Associated Degradation (ERAD). We have shown in the past that the
      degree of ERAD of mutant GCase correlates with GD severity.Persistent presence of
      mutant, misfolded protein molecules in the ER leads to ER stress and evokes the
      unfolded protein response (UPR). METHODS: We investigated the presence of UPR in
      several GD models, using molecular and behavioral assays. RESULTS: Our results
      show the existence of UPR in skin fibroblasts from GD patients and carriers of GD
      mutations. We could recapitulate UPR in two different Drosophila models for
      carriers of GD mutations: flies heterozygous for the endogenous mutant GBA
      orthologs and flies expressing the human N370S or L444P mutant GCase variants. We
      encountered early death in both fly models, indicating the deleterious effect of
      mutant GCase during development. The double heterozygous flies, and the
      transgenic flies, expressing mutant GCase in dopaminergic/serotonergic cells
      developed locomotion deficit. CONCLUSION: Our results strongly suggest that
      mutant GCase induces the UPR in GD patients as well as in carriers of GD
      mutations and leads to development of locomotion deficit in flies heterozygous
      for GD mutations.

PMID- 24020506
TI  - Biotechnological approaches for field applications of chitooligosaccharides (COS)
      to induce innate immunity in plants.
AB  - Plants have evolved mechanisms to recognize a wide range of pathogen-derived
      molecules and to express induced resistance against pathogen attack. Exploitation
      of induced resistance, by application of novel bioactive elicitors, is an
      attractive alternative for crop protection. Chitooligosaccharide (COS) elicitors,
      released during plant fungal interactions, induce plant defenses upon
      recognition. Detailed analyses of structure/function relationships of bioactive
      chitosans as well as recent progress towards understanding the mechanism of COS
      sensing in plants through the identification and characterization of their
      cognate receptors have generated fresh impetus for approaches that would induce
      innate immunity in plants. These progresses combined with the application of
      chitin/chitosan/COS in disease management are reviewed here. In considering the
      field application of COS, however, efficient and large-scale production of
      desired COS is a challenging task. The available methods, including chemical or
      enzymatic hydrolysis and chemical or biotechnological synthesis to produce COS,
      are also reviewed.

PMID- 24020507
TI  - Effect of folate-targeted nanoparticle size on their rates of penetration into
      solid tumors.
AB  - Targeted therapies are emerging as a preferred strategy for the treatment of
      cancer and other diseases. To evaluate the impact of a high affinity targeting
      ligand on the rate and extent of tumor penetration of different sized
      nanomedicines, we have used intravital multiphoton microscopy to quantitate the
      kinetics of tumor accumulation of a homologous series of folate-PEG-rhodamine
      conjugates prepared with polyethylene glycols (PEG) of different molecular
      weights. We demonstrate that increasing the size of the folate-PEG-rhodamine
      conjugates results in both longer circulation times and slower tumor penetration
      rates. Although a "binding site barrier" is observed with the folate-linked
      polymers in folate receptor expressing tumors, ligand targeting eventually leads
      to increased tumor accumulation, with endocytosis of the targeted nanocarriers
      contributing to their enhanced tumor retention. Because the effects of
      nanocarrier size, shape, chemistry, and targeting ligand are interconnected and
      complex, we suggest that these parameters must be carefully optimized for each
      nanocarrier to ensure optimal drug delivery in vivo. 

PMID- 24020508
TI  - Nanoarchitectures with controllable anisotropic features in structures and
      properties from simple and robust holographic lithography.
AB  - Anisotropic nanostructures with precise orientations or sharp corners display
      unique properties that may be useful in a variety of applications; however,
      precise control over the anisotropy of geometric features, using a simple and
      reproducible large-area fabrication technique, remains a challenge. Here, we
      report the fabrication of highly uniform polymeric and metallic nanostructure
      arrays prepared using prism holographic lithography (HL) in such a way that the
      isotropy that can be readily and continuously tuned. The prism position on the
      sample stage was laterally translated to vary the relative intensities of the
      four split beams, thereby tuning the isotropy of the resulting polymer
      nanostructures through the following shapes: circular nanoholes, elliptical
      nanoholes, and zigzag-shaped nanoarrays. Corresponding large-area, defect-free
      anisotropic metallic nanostructures could then be fabricated using an HL-featured
      porous polymer structure as a milling mask. Removal of the polymer mask left
      zigzag-shaped metallic nanostructure arrays in which nanogaps separated adjacent
      sharp edges. These structures displayed two distinct optical properties,
      depending on the direction along which the excitation beam was polarized
      (longitudinal and transverse modes) incident on the array. Furthermore,
      bidirectional anisotropic wetting was observed on the anisotropic polymer
      nanowall array surface. 

PMID- 24020509
TI  - Training based on ligand efficiency improves prediction of bioactivities of
      ligands and drug target proteins in a machine learning approach.
AB  - Machine learning methods based on ligand-protein interaction data in bioactivity
      databases are one of the current strategies for efficiently finding novel lead
      compounds as the first step in the drug discovery process. Although previous
      machine learning studies have succeeded in predicting novel ligand-protein
      interactions with high performance, all of the previous studies to date have been
      heavily dependent on the simple use of raw bioactivity data of ligand potencies
      measured by IC50, EC50, K(i), and K(d) deposited in databases. ChEMBL provides us
      with a unique opportunity to investigate whether a machine-learning-based
      classifier created by reflecting ligand efficiency other than the IC50, EC50,
      K(i), and Kd values can also offer high predictive performance. Here we report
      that classifiers created from training data based on ligand efficiency show
      higher performance than those from data based on IC50 or K(i) values. Utilizing
      GPCRSARfari and KinaseSARfari databases in ChEMBL, we created IC50- or K(i)-based
      training data and binding efficiency index (BEI) based training data then
      constructed classifiers using support vector machines (SVMs). The SVM classifiers
      from the BEI-based training data showed slightly higher area under curve (AUC),
      accuracy, sensitivity, and specificity in the cross-validation tests. Application
      of the classifiers to the validation data demonstrated that the AUCs and
      specificities of the BEI-based classifiers dramatically increased in comparison
      with the IC50- or K(i)-based classifiers. The improvement of the predictive power
      by the BEI-based classifiers can be attributed to (i) the more separated
      distributions of positives and negatives, (ii) the higher diversity of negatives
      in the BEI-based training data in a feature space of SVMs, and (iii) a more
      balanced number of positives and negatives in the BEI-based training data. These
      results strongly suggest that training data based on ligand efficiency as well as
      data based on classical IC50, EC50, K(d), and K(i) values are important when
      creating a classifier using a machine learning approach based on bioactivity
      data.

PMID- 24020510
TI  - Coping strategies of older rural Bangladeshi women with health problems.
AB  - In this study we explore the strategies used by older women to cope with their
      ill health, in order to provide insight into how they might be drawn to use
      modern health services. We used qualitative methods to collect data from 17 older
      women living in Bibirchar Union, Sherpur District, Bangladesh. Participants
      reported that they utilized both emotion-focused and problem-focused strategies,
      and that many of these were faith-based. Health policymakers need to acknowledge
      these strategies in the delivery of health care if older women are to take up
      health promotion activities and engage with the modern health care system. 

PMID- 24020512
TI  - Hospital-based influenza morbidity and mortality surveillance system for
      influenza-like illnesses: a comparison with national influenza surveillance
      systems.
AB  - The Hospital-based Influenza Morbidity and Mortality (HIMM) surveillance system
      is an emergency room (ER)-based influenza surveillance system in Korea that was
      established in 2011. The system was established under the assumption that
      integrated clinical and virologic surveillance could be performed rapidly and
      easily at seven tertiary hospitals' ER. Here, we assessed the correlation between
      data generated from the HIMM surveillance system and the Korean national
      influenza surveillance systems during the 2011-2012 influenza season using cross
      correlation analysis and found strong correlations. Rapid antigen-test-based HIMM
      surveillance would predict the start of influenza epidemic earlier than pre
      existing influenza-like-illness-based surveillance. 

PMID- 24020511
TI  - Histological evaluation of bone formation adjacent to dental implants with a
      novel apical chamber design: preliminary data in the rabbit model.
AB  - BACKGROUND: Wound healing events after implant placement will vary according to
      the extent of the necrotic zone. PURPOSE: The goal of the present study was to
      evaluate bone healing around titanium implants with a novel apical chamber
      design. MATERIALS AND METHODS: Titanium implants grade 4 were turned with
      different apex design. Control implants had a self tapping design with centric
      cutting grooves. Test implants exhibited eccentric cutting grooves interconnected
      by a hollow chamber. A total of 60 implants were installed in the femur/tibia of
      10 rabbits for histological analysis. RESULTS: After 1 week, immature bone
      formation started at the cortical level of the test implants associated to
      scalloped contours indicative of bone resorption. Control implants failed to show
      new bone formation, and the space within the threads was filled mainly by red
      blood cells and surgical debris. Bone contact values showed no difference after 1
      week, and significant higher values for test implants showed likewise after 4
      weeks compared with control implants in the tibia. CONCLUSION: This experimental
      study verifies the beneficial effect of bone formation in the chamber at the
      apical part of the fixture coupled to a faster bone healing to implants placed in
      dense bone.

PMID- 24020514
TI  - Dynamics of glass forming ammonia hydrates.
AB  - The dielectric relaxation of ammonia-water mixtures was studied for a range of
      NH3 mole fractions x. For 0.01 <= x < 0.33, the samples can be supercooled
      relatively easily. In this composition range, the relaxation strength is
      proportional to x. The dielectric relaxation times display a super-Arrhenius
      behavior, are independent of the NH3 content in the specified range, and, for T >
      250 K, line up smoothly with those of pure water. The relaxation behavior of
      glass forming ammonia hydrates was also investigated using nuclear magnetic
      resonance techniques including deuteron relaxometry and stimulated-echo
      spectroscopy, as well as static field-gradient proton diffusometry. These
      experiments yielded additional insights into the rotational and translational
      dynamics of ammonia hydrates. 

PMID- 24020513
TI  - Evaluation of neutrophil gelatinase-associated lipocalin as a marker of kidney
      injury in dogs.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common and often fatal disorder in
      dogs. HYPOTHESIS: Urine neutrophil gelatinase-associated lipocalin
      (NGAL)/creatinine ratio is a sensitive and specific biomarker of AKI in dogs.
      ANIMALS: Ninety-four dogs. METHODS: Prospective study. Dogs were classified as
      follows: (1) healthy dogs, (2) dogs with lower urinary tract disorders, (3) dogs
      with chronic kidney disease (CKD), (4) dogs with azotemic International Renal
      Interest Society (IRIS) AKI Grades II-V, and (5) dogs with IRIS AKI Grade I
      (nonazotemic). Urinary NGAL was quantitated in each dog using an ELISA assay and
      concentrations were expressed as a ratio to urinary creatinine concentration from
      the same specimen, and designated the urinary NGAL/creatinine ratio (UNCR).
      RESULTS: There was a significant difference in UNCR among the study groups (P <
      .001). Both the azotemic and nonazotemic AKI groups had higher UNCR when compared
      with all other groups (P < .001 for all pairs). There was a statistically
      significant difference in UNCR between dogs diagnosed with CKD compared with dogs
      with lower urinary tract diseases (P = .005) as well as between dogs with CKD and
      healthy dogs (P = .001). Receiver operator characteristics (ROC) analysis of UNCR
      as an indicator of azotemic and nonazotemic AKI had an area under the ROC curve
      of 0.94 and 0.96, respectively. CONCLUSIONS AND CLINICAL RELEVANCE:
      NGAL/creatinine ratio is a sensitive and specific marker of AKI. It can be used
      to screen patients at risk for AKI and can be utilized to diagnose milder forms
      of AKI potentially earlier in the course of the disease.

PMID- 24020515
TI  - A fatal case of hypermagnesemia caused by ingesting magnesium chloride as a folk
      remedy.
AB  - We report a fatal case of hypermagnesemia caused by oral ingestion of milk
      containing magnesium chloride as a folk remedy. The autopsy of the 75-year-old
      woman showed no injury or illness as the cause of death. Neither alcohol nor
      controlled drugs were found by the toxicological analysis. Her posthumous serum
      magnesium concentration was 10.2 mg/dL. The concentration of magnesium in serum
      was higher than that of the previous reports. Therefore, the cause of death was
      considered to be hypermagnesemia. Recently, the prescription drugs, over-the
      counter drugs, and health foods containing magnesium are consumed as supplements
      in the world, and their potential toxicity should be recognized.

PMID- 24020517
TI  - Overweight and obesity in youth with developmental disabilities: a call to
      action.
AB  - Elevated weight status has become a leading problem for adults and children
      around the world, regardless of the presence or lack of disability. Youth with
      intellectual and developmental disabilities are more vulnerable than the typical
      population to overweight in recent decades, and these individuals often
      experience overweight and obesity at higher rates than their typically developing
      peers. Young people with disabilities have many circumstances, beyond those of
      typically developing children, which increase their risk for greater body mass.
      These include greater medication use, having syndromes with obesity as an
      associated symptom, and possessing altered eating habits related to their
      disability. We discuss obesity-related health risks, possible weight management
      options, recommendations for weight maintenance or loss, and future research.
      Although most professionals who work with youth having developmental disabilities
      do not have great expertise in nutrition and weight management, we must
      collectively recognise the importance of weight issues for quality of life of
      these individuals and work with them in maintaining healthy lifestyles.
      Intervention options, both for caregivers and for health professionals, are
      discussed. 

PMID- 24020518
TI  - Age biases in a large HIV and sexual behaviour-related internet survey among MSM.
AB  - BACKGROUND: Behavioural data from MSM are usually collected in non-representative
      convenience samples, increasingly on the internet. Epidemiological data from such
      samples might be useful for comparisons between countries, but are subject to
      unknown participation biases. METHODS: Self-reported HIV diagnoses from
      participants of the European MSM Internet Survey (EMIS) living in the Czech
      Republic, Germany, The Netherlands, Portugal, Sweden and the United Kingdom were
      compared with surveillance data, for both the overall diagnosed prevalence and
      for new diagnoses made in 2009. Country level prevalence and new diagnoses rates
      per 100 MSM were calculated based on an assumed MSM population size of 3% of the
      adult male population. Survey-surveillance discrepancies (SSD) for survey
      participation, diagnosed HIV prevalence and new HIV diagnoses were determined as
      ratios of proportions. Results are calculated and presented by 5-year age groups
      for MSM aged 15-64. RESULTS: Surveillance derived estimates of diagnosed HIV
      prevalence among MSM aged 15-64 ranged from 0.63% in the Czech Republic to 4.93%
      in The Netherlands. New HIV diagnoses rates ranged between 0.10 per 100 MSM in
      the Czech Republic and 0.48 per 100 in The Netherlands. Self-reported rates from
      EMIS were consistently higher, with prevalence ranging from 2.68% in the Czech
      Republic to 12.72% in The Netherlands, and new HIV diagnoses rates from 0.36 per
      100 in Sweden to 1.44 per 100 in The Netherlands. Across age groups, the survey
      surveillance discrepancies (SSD) for new HIV diagnoses were between 1.93 in UK
      and 5.95 in the Czech Republic, and for diagnosed prevalence between 1.80 in
      Germany and 4.26 in the Czech Republic.Internet samples of MSM were skewed
      towards younger age groups when compared to an age distribution of the general
      adult male population. Survey-surveillance discrepancies (SSD) for EMIS
      participation were inverse u-shaped across the age range. The two HIV-related SSD
      were u- or j-shaped with higher values for the very young and for older MSM. The
      highest discrepancies between survey and surveillance data regarding HIV
      prevalence were observed in the oldest age group in Sweden and the youngest age
      group in Portugal. CONCLUSION: Internet samples are biased towards a lower median
      age because younger men are over-represented on MSM dating websites and therefore
      may be more likely to be recruited into surveys. Men diagnosed with HIV were over
      represented in the internet survey, and increasingly so in the older age groups.
      A similar effect was observed in the age groups younger than 25 years. Self
      reported peak prevalence and peak HIV diagnoses rates are often shifted to higher
      age groups in internet samples compared to surveillance data. Adjustment for age
      effects on online accessibility should be considered when linking data from
      internet surveys with surveillance data.

PMID- 24020519
TI  - Early exposure to allergens: a new window of opportunity for non-communicable
      disease prevention in complementary feeding?
AB  - Recent findings suggest that an early exposure to dietary antigens may be more
      protective towards allergy than a later introduction even in high-risk infants.
      The consequent earlier introduction of food items such as egg yolk and oily fish,
      together with breastfeeding continuation through the first year, could contribute
      to reducing protein and increasing fat supply, respectively. These changes might
      have a role in the overall prevention of non-communicable disorders of adulthood.

PMID- 24020522
TI  - NMC must strike the right balance on new system.

PMID- 24020523
TI  - Third-party feedback could be used to assess nurses' fitness to practise.

PMID- 24020521
TI  - Tracking NF-kappaB activity in tumor cells during ovarian cancer progression in a
      syngeneic mouse model.
AB  - BACKGROUND: Nuclear factor-kappa B (NF-kappaB) signaling is an important link
      between inflammation and peritoneal carcinomatosis in human ovarian cancer. Our
      objective was to track NF-kappaB signaling during ovarian cancer progression in a
      syngeneic mouse model using tumor cells stably expressing an NF-kappaB reporter.
      METHODS: ID8 mouse ovarian cancer cells stably expressing an NF-kappaB-dependent
      GFP/luciferase (NGL) fusion reporter transgene (ID8-NGL) were generated, and
      injected intra-peritoneally into C57BL/6 mice. NGL reporter activity in tumors
      was non-invasively monitored by bioluminescence imaging and measured in
      luciferase assays in harvested tumors. Ascites fluid or peritoneal lavages were
      analyzed for inflammatory cell and macrophage content, and for mRNA expression of
      M1 and M2 macrophage markers by quantitative real-time RT-PCR. 2-tailed Mann
      Whitney tests were used for measuring differences between groups in in vivo
      experiments. RESULTS: In ID8-NGL cells, responsiveness of the reporter to NF
      kappaB activators and inhibitors was confirmed in vitro and in vivo. ID8-NGL
      tumors in C57BL/6 mice bore histopathological resemblance to human high-grade
      serous ovarian cancer and exhibited similar peritoneal disease spread. Tumor NF
      kappaB activity, measured by the NGL reporter and by western blot of nuclear p65
      expression, was markedly elevated at late stages of ovarian cancer progression.
      In ascites fluid, macrophages were the predominant inflammatory cell population.
      There were elevated levels of the M2-like pro-tumor macrophage marker, mannose
      receptor, during tumor progression, and reduced levels following NF-kappaB
      inhibition with thymoquinone. CONCLUSIONS: Our ID8-NGL reporter syngeneic model
      is suitable for investigating changes in tumor NF-kappaB activity during ovarian
      cancer progression, how NF-kappaB activity influences immune cells in the tumor
      microenvironment, and effects of NF-kappaB-targeted treatments in future studies.

PMID- 24020528
TI  - CCTV on wards could encourage better practice, says professor.

PMID- 24020520
TI  - Oncolytic viruses as therapeutic cancer vaccines.
AB  - Oncolytic viruses (OVs) are tumor-selective, multi-mechanistic antitumor agents.
      They kill infected cancer and associated endothelial cells via direct oncolysis,
      and uninfected cells via tumor vasculature targeting and bystander effect.
      Multimodal immunogenic cell death (ICD) together with autophagy often induced by
      OVs not only presents potent danger signals to dendritic cells but also
      efficiently cross-present tumor-associated antigens from cancer cells to
      dendritic cells to T cells to induce adaptive antitumor immunity. With this
      favorable immune backdrop, genetic engineering of OVs and rational combinations
      further potentiate OVs as cancer vaccines. OVs armed with GM-CSF (such as T-VEC
      and Pexa-Vec) or other immunostimulatory genes, induce potent anti-tumor immunity
      in both animal models and human patients. Combination with other immunotherapy
      regimens improve overall therapeutic efficacy. Coadministration with a HDAC
      inhibitor inhibits innate immunity transiently to promote infection and spread of
      OVs, and significantly enhances anti-tumor immunity and improves the therapeutic
      index. Local administration or OV mediated-expression of ligands for Toll-like
      receptors can rescue the function of tumor-infiltrating CD8+ T cells inhibited by
      the immunosuppressive tumor microenvironment and thus enhances the antitumor
      effect. Combination with cyclophosphamide further induces ICD, depletes Treg, and
      thus potentiates antitumor immunity. In summary, OVs properly armed or in
      rational combinations are potent therapeutic cancer vaccines. 

PMID- 24020533
TI  - Late diagnosis of constipation in older people costs L 42m a year.

PMID- 24020535
TI  - NHS should tap into experience of defence nurses, says England's CNO.

PMID- 24020539
TI  - Too much pressure: NHS employers must invest in nurses' wellbeing.

PMID- 24020545
TI  - Psoriasis.

PMID- 24020546
TI  - The war on stress.
AB  - Nurses over 40 are at greater risk of burnout than younger ones due to
      'compassion fatigue' after years of service and pressures such as caring for
      elderly parents. Employers need to adjust working conditions and allow them time
      to refresh their practice. Older nurses should avoid taking on too many
      responsibilities -and enjoy their social life.

PMID- 24020547
TI  - Admirals to the rescue.
AB  - A nursing service set up by the Royal British Legion and Dementia UK is
      supporting the families of former service personnel. The nurses give practical
      help and suggest coping strategies to ease the agitation of the person with
      dementia. Families with a background in the armed forces appreciate the British
      Legion connection.

PMID- 24020554
TI  - Starting out - the things I wish I'd known about all the highs and lows of
      training.

PMID- 24020560
TI  - Cuts to nursing posts exacerbate an uncaring conveyor-belt system.

PMID- 24020561
TI  - Retaliation is not the solution to the human suffering in Syria.

PMID- 24020562
TI  - Please sign my petition urging the UN to end all wars by 2030.

PMID- 24020563
TI  - 'White lies' can sometimes be kinder for people with dementia.

PMID- 24020564
TI  - Zero-hours contracts offer no guarantees of anything at all.

PMID- 24020565
TI  - Basics of numeracy should be an integral part of nurse training.

PMID- 24020566
TI  - Here's to the growing success of green-fingered therapy.

PMID- 24020567
TI  - The lack of genital mutilation prosecutions is a disgrace.

PMID- 24020569
TI  - Patient choice? Some doctors still think they know best.

PMID- 24020575
TI  - The Mental Capacity Act 2005: considerations for nursing practice.
AB  - This article explores the main elements of the Mental Capacity Act 2005 and the
      implications for nurses. Many vulnerable adults have impaired capacity, and it is
      vital that nurses are confident in understanding when and how to assess an
      individual's capacity. Nurses should be supported and given training to ensure
      they can apply the principles of the Mental Capacity Act 2005 to practice. It is
      also important that nurses have a good understanding of the deprivation of
      liberty safeguards and can identify when their interventions may deprive patients
      of their liberty, ensuring that these are only undertaken legally. 

PMID- 24020576
TI  - Spiritual care at the end of life.
AB  - With increasing focus on providing spiritual care at the end of life, healthcare
      professionals and those involved in policy development are questioning how to
      make a 'good' death the expectation, rather than the exception. However, there is
      a lack of awareness of the importance of spirituality to patients' lives, and how
      good spiritual care can enhance quality of life and improve patient outcomes.
      This article examines the role of spirituality in palliative care, focusing on
      spiritual assessment, communication and compassion in nursing. The article
      attempts to provide a working definition of spirituality, focusing on who should
      provide spiritual care and the difficulties in meeting the spiritual needs of
      individuals at the end of life. Strategies to promote the spiritual wellbeing of
      the patient are discussed. 

PMID- 24020577
TI  - Reducing cardiovascular disease risk: cholesterol and diet.
AB  - Addressing cardiovascular disease (CVD) is a priority for all involved in health
      promotion. Identifying those at risk and implementing strategies to reduce the
      incidence of CVD are important issues for government and healthcare providers.
      This article discusses risk assessment and medical intervention, and provides a
      detailed analysis of the role of diet in cholesterol reduction. The nurse's role
      in assisting patients to make dietary changes is examined and practical
      information on empowering patients to manage their health is provided. 

PMID- 24020578
TI  - Early-stage dementia.

PMID- 24020579
TI  - Inspiring a generation.

PMID- 24020580
TI  - Preparing for the end.

PMID- 24020582
TI  - Stepping in to help detainees.

PMID- 24020583
TI  - Championing change by 'ticking boxes'.

PMID- 24020584
TI  - Quercetin attenuates carbon tetrachloride-induced testicular damage in rats.
AB  - This study was conducted to investigate the effect of quercetin on carbon
      tetrachloride (CCl4 )-induced sperm damages, testicular apoptosis and oxidative
      stress in male rats. Group 1 served as control, group 2 was treated with only
      quercetin, group 3 was treated with only CCl4 and group 4 received CCl4 +
      quercetin. All administrations were performed by gavage and maintained for 10
      weeks. CCl4 administration caused significant decreases in absolute and relative
      reproductive organ weights, sperm motility, concentration and testicular
      glutathione peroxidase (GSH-Px) and catalase (CAT) activities, and significant
      increases in lipid peroxidation (LPO) level, abnormal sperm rate and testicular
      apoptotic cell index, along with some histopathological damages when compared to
      the control group. However, administration of CCl4 together with quercetin
      provided statistically significant improvements in LPO level, abnormal sperm
      rate, the degree of histopathological lesions and testicular apoptotic cell index
      when compared to only CCl4 group. In addition, improvements observed in absolute
      and relative weights of reproductive organs, sperm motility and concentration,
      and testicular GSH-Px and CAT activities in group 4 were statistically
      insignificant when compared to only CCl4 group. In conclusion, quercetin has
      antiperoxidative effect, and its oral administration attenuates the CCl4 -induced
      some damages in male reproductive organs and cells by decreasing the LPO.

PMID- 24020585
TI  - Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4
      thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and
      antitumor agents.
AB  - Since the first histone deacetylase (HDAC) inhibitor (Zolinza(r), widely known as
      suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug
      Administration for the treatment of T-cell lymphoma in 2006, the search for newer
      HDAC inhibitors has attracted a great deal of interest of medicinal chemists
      worldwide. As a continuity of our ongoing research in this area, we designed and
      synthesized a series of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic
      acids as analogues of SAHA and evaluated their biological activities. A number of
      compounds in this series, for example, N(1)-hydroxy-N(8)-(5-(2-chlorophenyl)
      1,3,4-thiadiazol-2-yl)octandiamide (5b), N(1)-hydroxy-N(8)-(5-(3-chlorophenyl
      1,3,4-thiadiazol-2-yl)octandiamide (5c) and N(1)-hydroxy-N(8)-(5-(4-chlorophenyl)
      1,3,4-thiadiazol-2-yl)octandiamide (5d), were found to possess potent anticancer
      cytotoxicity and HDAC inhibition effects. Compounds 5b-d were generally two- to
      five-fold more potent in terms of cytotoxicity compared to SAHA against five
      cancer cell lines tested. Docking studies revealed that these hydroxamic acid
      displayed higher affinities than SAHA toward HDAC8.

PMID- 24020587
TI  - Oxidative DNA damage and mammary cell proliferation by alcohol-derived
      salsolinol.
AB  - Drinking alcohol is a risk factor for breast cancer. Salsolinol (SAL) is
      endogenously formed by a condensation reaction of dopamine with acetaldehyde, a
      major ethanol metabolite, and SAL is detected in blood and urine after alcohol
      intake. We investigated the possibility that SAL can participate in tumor
      initiation and promotion by causing DNA damage and cell proliferation, leading to
      alcohol-associated mammary carcinogenesis. SAL caused oxidative DNA damage
      including 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), in the presence of
      transition metal ions, such as Cu(II) and Fe(III)EDTA. Inhibitory effects of
      scavengers on SAL-induced DNA damage and the electron spin resonance study
      indicated the involvement of H2O2, which is generated via the SAL radical.
      Experiments on scavengers and site specificity of DNA damage suggested .OH
      generation via a Fenton reaction and copper-peroxide complexes in the presence of
      Fe(III)EDTA and Cu(II), respectively. SAL significantly increased 8-oxodG
      formation in normal mammary epithelial MCF-10A cells. In addition, SAL induced
      cell proliferation in estrogen receptor (ER)-negative MCF-10A cells, and the
      proliferation was inhibited by an antioxidant N-acetylcysteine and an epidermal
      growth factor receptor (EGFR) inhibitor AG1478, suggesting that reactive oxygen
      species may participate in the proliferation of MCF-10A cells via EGFR
      activation. Furthermore, SAL induced proliferation in estrogen-sensitive breast
      cancer MCF-7 cells, and a surface plasmon resonance sensor revealed that SAL
      significantly increased the binding activity of ERalpha to the estrogen response
      element but not ERbeta. In conclusion, SAL-induced DNA damage and cell
      proliferation may play a role in tumor initiation and promotion of multistage
      mammary carcinogenesis in relation to drinking alcohol.

PMID- 24020586
TI  - Nestin-expressing stem cells from the hair follicle can differentiate into motor
      neurons and reduce muscle atrophy after transplantation to injured nerves.
AB  - We have previously shown that nestin-expressing hair follicle stem cells from the
      mouse and human are multipotent and can differentiate into many cell types,
      including neurons and glial cells. The nestin-expressing hair follicle stem cells
      can effect nerve and spinal cord repair upon transplantation in mouse models. In
      the present study, nestin-expressing hair follicle stem cells expressing red
      fluorescent protein (RFP) were induced by retinoic acid and fetal bovine serum to
      differentiate and then transplanted together with Matrigel into the transected
      distal sciatic or tibial nerve stump of transgenic nude mice ubiquitously
      expressing green fluorescent protein (GFP). Control mice were transplanted with
      Matrigel only. The transplanted cells appeared neuron like, with large round
      nuclei and long extensions. Immunofluorescence staining showed that some of the
      transplanted cells in the distal nerve stump expressed the neuron marker Tuj1 as
      well as motor neuron markers Isl 1/2 and EN1. These transplanted cells contacted
      each other as well as host nerve fibers. Two weeks post-transplantation, nerve
      fibers in the distal sciatic nerve stump of the transplanted mice had greater
      expression of motor neuron markers and neurotrophic factor-3 than those in the
      Matrigel-only transplanted mice. Muscle fiber areas in the nestin-expressing stem
      cell plus Matrigel-transplanted animals were much bigger than that in the
      Matrigel-only transplanted animals after 4 weeks. The present results suggest
      that transplanted nestin-expressing hair follicle stem cells can differentiate
      into motor neurons and reduce muscle atrophy after sciatic nerve transection.
      This study demonstrates a new and accessible neuron source to reduce muscle
      atrophy after nerve injury. 

PMID- 24020588
TI  - Temporal vocal features suggest different call-pattern generating mechanisms in
      mice and bats.
AB  - BACKGROUND: Mice produce ultrasonic vocalizations in various inter-individual
      encounters and with high call rates. However, it is so far virtually unknown how
      these vocal patterns are generated. On the one hand, these vocal patterns could
      be embedded into the normal respiratory cycle, as happens in bats and other
      mammals that produce similar call rates and frequencies. On the other, mice could
      possess distinct vocal pattern generating systems that are capable of modulating
      the respiratory cycle, which is what happens in non-human and human primates. In
      the present study, we investigated the temporal call patterns of two different
      mammalian species, bats and mice, in order to differentiate between these two
      possibilities for mouse vocalizations. Our primary focus was on comparing the
      mechanisms for the production of rapid, successive ultrasound calls of comparable
      frequency ranges in the two species. RESULTS: We analyzed the temporal call
      pattern characteristics of mice, and we compared these characteristics to those
      of ultrasonic echolocation calls produced by horseshoe bats. We measured the
      distributions of call durations, call intervals, and inter-call intervals in the
      two species. In the bat, and consistent with previous studies, we found that call
      duration was independent of corresponding call intervals, and that it was
      negatively correlated with the corresponding inter-call interval. This indicates
      that echolocation call production mechanisms in the bat are highly correlated
      with the respiratory cycle. In contrast, call intervals in the mouse were
      directly correlated with call duration. Importantly, call duration was not, or
      was only slightly, correlated with inter-call intervals, consistent with the idea
      that vocal production in the mouse is largely independent of the respiratory
      cycle. CONCLUSIONS: Our findings suggest that ultrasonic vocalizations in mice
      are produced by call-pattern generating mechanisms that seem to be similar to
      those that have been found in primates. This is in contrast to the production
      mechanisms of ultrasonic echolocation calls in horseshoe bats. These results are
      particularly interesting, especially since mouse vocalizations have recently
      attracted increased attention as potential indicators for the degree of
      progression of several disease patterns in mouse models for neurodegenerative and
      neurodevelopmental disorders of humans.

PMID- 24020589
TI  - Probing heme vibrational anisotropy: an imidazole orientation effect?
AB  - The complete iron vibrational spectrum of the five-coordinate high-spin complex
      [Fe(OEP)(2-MeHIm)], where OEP = octaethylporphyrinato and 2-MeHIm = 2
      methylimidazole, has been obtained by oriented single-crystal nuclear resonance
      vibrational spectroscopy (NRVS) data. Measurements have been made in three
      orthogonal directions, which provides quantitative information for all iron
      motion. These experimental data, buttressed by density functional theory (DFT)
      calculations, have been used to define the effects of the axial ligand
      orientation. Although the axial imidazole removes the degeneracy in the in-plane
      vibrations, the imidazole orientation does not appear to control the direction of
      the in-plane iron motion. This is in contrast to the effect of the imidazolate
      ligand, as defined by DFT calculations, which does have substantial effects on
      the direction of the in-plane iron motion. The axial NO ligand has been found to
      have the strongest orientational effect (Angew. Chem., Int. Ed., 2010, 49, 4400).
      Thus the strength of the directional properties are in the order NO > imidazolate
      > imidazole, consistent with the varying strength of the Fe-ligand bond. 

PMID- 24020591
TI  - Unusual dynamic dewetting behavior of smooth perfluorinated hybrid films:
      potential advantages over conventional textured and liquid-infused perfluorinated
      surfaces.
AB  - From a viewpoint of reducing the burden on the environment and human health, an
      alternative method for preparing liquid-repellent surfaces without relying on the
      long perfluorocarbons (C((X-1)/2)F(X), X >= 17) has been strongly demanded
      lately. In this study, we have successfully demonstrated that dynamic
      dewettability toward various probe liquids (polar and nonpolar liquids with high
      or low surface tension) can be tuned by not only controlling surface chemistries
      (surface energies) but also the physical (solid-like or liquid-like) nature of
      the surface. We prepared smooth and transparent organic-inorganic hybrid films
      exhibiting unusual dynamic dewetting behavior toward various probe liquids using
      a simple sol-gel reaction based on the co-hydrolysis and co-condensation of a
      mixture including a range of perfluoroalkylsilanes (FASX, C((X
      1)/2)F(X)CH2CH2Si(OR)3, where X = 3, 9, 13, and 17) and tetramethoxysilane
      (Si(OCH3)4, TMOS). Dynamic contact angle (CA) and substrate tilt angle (TA)
      measurements confirmed that our FASX-hybrid films exhibited excellent dynamic
      dewetting properties and were mostly independent of the length of perfluoroalkyl
      (Rf) groups. For example, 10 MUL droplets of ultralow surface tension liquids
      (e.g., diethyl ether (gamma = 16.26 dyn/cm) and n-pentane (gamma = 15.51 dyn/cm))
      could move easily on our FAS9-, FAS13-, and FAS17-hybrid film surfaces at low
      substrate TAs (<4 degrees ) without pinning. This is comparable or superior to
      the best perfluorinated textured and flat surfaces reported so far. This
      exceptional dynamic dewetting behavior appeared only when TMOS molecules were
      added to the precursor solutions; we assume this is due to co-condensed TMOS
      derived silica species working as spacers between the neighboring Rf chains,
      enabling them to rotate freely and in doing so provide a surface with liquid-like
      properties. This led to the distinguished dynamic dewettability of our hybrid
      films, regardless of the small static CAs. Our FASX-hybrid films also displayed
      excellent chemical and physical durability against thermal stress (~250  degrees
      C), high-temperature (150  degrees C) oil vapor, and various other media
      (perfluoro liquid, boiling water, and weak acid) without degrading their dynamic
      dewettability. Such exceptional durability has been rarely seen on conventional
      perfluorinated surfaces reported so far.

PMID- 24020590
TI  - Serum levels of albumin-amyloid beta complexes are decreased in Alzheimer's
      disease.
AB  - AIM: Decreased amyloid beta (Abeta) clearance from the brain to blood might play
      a key role in the development of Alzheimer's disease (AD). Abeta is normally
      bound to and transported by albumin in blood, thus possibly maintaining constant
      concentration of free Abeta in the blood. We therefore hypothesized that
      decreased blood levels of albumin-Abeta complexes could be associated with
      decreased Abeta removal from the brain to blood, resulting in Abeta accumulation
      in the brain. METHODS: We carried out a cross-sectional investigation of the
      association between serum levels of albumin-Abeta complexes (SLAAC) and AD
      prevalence in 89 patients who visited our outpatient clinic, and gave written
      informed consent between August 2008 and May 2012. RESULTS: We confirmed 45 cases
      of AD. Low SLAAC was associated with an increased prevalence of AD (OR 0.27; 95%
      CI 0.14-0.51) in a univariable logistic model and multivariable logistic models.
      In addition, decreased SLAAC was associated with decreased levels of Abeta42 in
      CSF (r = 0.38, P = 0.0221) and increased levels of p-tau in CSF (r = -0.43, P =
      0.0090), findings that have been shown to be associated with AD progression.
      CONCLUSIONS: This novel method might be very useful for monitoring of the
      progression of AD.

PMID- 24020592
TI  - Universal patient-centred care: can we achieve it?

PMID- 24020593
TI  - Patient-centred care: is it the key to stemming the tide?

PMID- 24020594
TI  - Making patient-centred care a reality in the slums of eastern Nairobi.

PMID- 24020595
TI  - Evaluating the output of transformational patient-centred nurse training in
      Ethiopia.
AB  - BACKGROUND: To strengthen efforts in prevention, proper care and control of
      tuberculosis (TB) in Ethiopia, the Ethiopian Nurses Association (ENA) trained
      nurses in the use of patient-centred transformational training methods developed
      by the International Council of Nurses (ICN). OBJECTIVES: To evaluate the impact
      of the training course on patient outcomes, changes in practice and the numbers
      of additional people trained following the training. METHODS: During the TB
      project period, 115 nurses were trained in the care, prevention and management of
      TB and multidrug-resistant TB (TB/MDR-TB). The effect of this training was
      evaluated by telephone, during annual review meetings from 2010 to 2012 and at on
      site assessment visits conducted from December 2012 to February 2013. These
      visits were conducted in 11 health facilities (7 hospitals and 4 health centres),
      where trained nurses and managers were interviewed using a checklist. RESULTS: A
      total of 14 nurses were interviewed. All of them made a schedule and offered
      training on TB/MDR-TB for health care providers, clients and/or communities.
      Practical changes and improvements in patient outcomes were observed in the
      health facilities where nurses had been trained. DISCUSSION: Results showed that
      the transformational patient-centred training methods used led to ongoing
      training provision and practical improvements. In addition, it was found that
      addressing health care providers and the community at large through awareness
      raising by trained nurses has the potential to bring about behavioural change
      likely to reduce the risk of transmission. Using a variety of methods was found
      to be a cost-effective and realistic way of evaluating the effect of training.

PMID- 24020596
TI  - Patient-centered primary health care: synergy potential for health systems
      strengthening.
AB  - The ultimate goal of government health systems is to provide highly effective
      equitable services that save lives and reduce morbidity and mortality. The
      pressure to conform to duplicative global and donor initiatives compounds
      existing challenges to health systems strengthening such as shortages of human
      resources for health, weak supply chains, inadequate laboratory services and
      parallel data management systems. This article illustrates how primary health
      care, as the point of entry into the health care system for the majority of
      individuals in sub-Saharan Africa, should be strengthened to ensure that
      individuals and their communities receive essential, holistic care. 

PMID- 24020598
TI  - Nurse-managed care for health care workers in southern Africa.
AB  - In Swaziland, the health care system is experiencing severe scarcity of health
      care workers (HCWs) due to difficult working conditions, migration and the human
      immunodeficiency virus (HIV) pandemic. Nurses and other HCWs in Swaziland are
      personally as affected by communicable diseases as the general population. High
      levels of HIV and TB co-infection bring added complexity to care. The loss of
      skilled staff in key positions has had a particularly negative impact on the
      quality of care and service delivery. The Swaziland Nurses Association (SNA) has
      established a Centre for Comprehensive Wellness for HCWs in the public and
      private sector and their immediate families to support the health workforce. 

PMID- 24020597
TI  - Health care workers' fears associated with working in multidrug- and or
      extensively-resistant tuberculosis wards in South Africa.
AB  - SETTING: Twenty-four drug-resistant tuberculosis (TB) hospitals and wards across
      all nine provinces of South Africa. OBJECTIVE: To assess health care workers'
      (HCWs') fears of working in multidrug-resistant TB (MDR-TB) or extensively drug
      resistant TB (XDR-TB) wards. DESIGN: A cross-sectional descriptive study was
      conducted from June to September 2009 in 24 drug-resistant TB hospitals across
      South Africa. HCWs completed a self-administered questionnaire, including one
      open-ended question regarding personal concerns about their fear of contracting
      MDR- or XDR-TB. Responses were analysed by content analysis. RESULTS: Among the
      24 hospitals, 499 HCWs were surveyed, of whom 363 (73%) responded to the open
      ended question: 286 (86%) were nurses, 38 (11%) medical officers and 10 (3%)
      others. Six major themes regarding fears associated with the personal risk of
      acquiring drug-resistant TB emerged. These included the fear of 1) developing MDR
      and XDR-TB, 2) the treatment course, 3) the financial implications, 4) family
      concerns, 5) working environment and 6) psychosocial issues. CONCLUSIONS: These
      data suggest that the greatest fear of HCWs working in drug-resistant TB wards is
      contracting MDR- or XDR-TB and infecting others. This fear may negatively impact
      the provision of quality patient-centred care, and highlights the need for
      training of HCWs in infection control measures, and specifically on how HCWs can
      protect themselves and others from developing TB.

PMID- 24020599
TI  - The contribution of nurses to a multi-disciplinary approach to patient care in
      Tomsk, Russia.
AB  - The Tomsk Oblast Tuberculosis (TB) services have accumulated unique experience in
      the area of TB detection, care and control through their collaboration with
      various international partners since 1994. Nurses account for about one half of
      all health care personnel in both in-patient and out-patient care sectors in
      Tomsk TB services, and they have been involved throughout in the planning and
      delivery of care. The authors believe that a holistic approach to service
      provision has led to positive results in TB programme outcomes, which are better
      than many in Russia, even with historically high rates of drug-resistant TB. 

PMID- 24020600
TI  - Tuberculosis peer educators: personal experiences of working with socially
      excluded communities in London.
AB  - SETTING: Peer education is a relatively unexplored intervention for tuberculosis
      (TB) control, particularly among socially excluded communities. In London, peer
      educators are used to raise awareness of TB and promote uptake of radiological
      screening among people using homeless and/or drug and alcohol treatment services.
      OBJECTIVE: To understand the motivation and personal impact of being a peer
      educator on people with experience of anti-tuberculosis treatment, homelessness
      and addiction. DESIGN: In-depth semi-structured interviews with peer educators
      were recorded and transcribed, and then analysed using a grounded theory approach
      to identify themes. Reflexivity and thick description were used to support
      transparency of findings. RESULTS: Becoming a peer educator supports individuals
      in making sense of past experiences and renewing their sense of self. The role
      places value on personal experience and the communication approach this supports.
      The project environment is an important motivator, providing the peer with
      structure, social support and respect. CONCLUSION: Being a peer educator with
      experience of homelessness and addiction can be beneficial and empowering and
      help long-term recovery. Peers are an underused resource for strengthening TB
      control among socially excluded populations. There is a need for further research
      into the contribution of peers to TB control, including analyses of economic
      effectiveness.

PMID- 24020601
TI  - Tuberculosis diagnostic pathway in a municipality in south-eastern Brazil.
AB  - OBJECTIVE: To analyse the pathway taken by tuberculosis (TB) patients from the
      first contact with the health services and the diagnosis of TB disease. METHOD:
      In a survey conducted in a south-eastern municipality of Brazil prioritised for
      TB control, a structured questionnaire was applied to 100 TB patients under
      treatment; secondary data recorded in two information systems were also collected
      for analysis. Diagrams were constructed to represent the patient pathway through
      the health services up to diagnosis. RESULTS: The emergency services were the
      point of entry into care for the majority of the patients. Those who first
      attended primary health care (PHC) centres needed to visit other health services
      for diagnosis. CONCLUSION: Our study shows that multiple visits to multiple
      health services are required for the majority of patients to be diagnosed with
      TB. It is necessary to reinforce the referral path established for TB diagnosis
      and communication among providers, who should play a clear role in obtaining
      early diagnosis.

PMID- 24020602
TI  - Community-based intervention to enhance provision of integrated TB-HIV and PMTCT
      services in South Africa.
AB  - OBJECTIVE: To conduct an impact assessment of an intervention to enhance the
      provision of community-based integrated services for tuberculosis (TB), human
      immunodeficiency virus (HIV) and prevention of mother-to-child transmission
      (PMTCT). METHODS: The intervention consisted of a combination of training of
      community care workers (CCWs), structural adjustments, harmonisation of scope of
      practice and stipend of CCWs and enhanced supervision of CCWs to provide
      comprehensive TB-HIV/PMTCT services in a rural South African district. A before
      and after study design was used with a household survey to assess the operational
      effectiveness of the intervention. Six clusters were randomised into intervention
      and control arms. Quantitative data were analysed using logistic regression,
      adjusting for cluster design. RESULTS: Logistic regression analyses of the survey
      data show that CCWs from the intervention arm performed better in the provision
      of TB-HIV/PMTCT services, such as screening for TB and sexually transmitted
      infections, adherence to anti-tuberculosis treatment and antiretroviral therapy
      and counselling on infant feeding compared to the control CCWs (P < 0.05).
      However, intervention CCWs performed worse in the integrated management of
      childhood illnesses education and social welfare referrals (P < 0.05). The uptake
      of HIV testing increased significantly in the intervention arm, from 55% to 78%
      (P < 0.001). CONCLUSION: The intervention was effective in enhancing the
      provision of community-based TB-HIV and PMTCT services. However, attention to
      other primary health care services is required to ensure that all key services
      are provided.

PMID- 24020603
TI  - The treatment journey of a patient with multidrug-resistant tuberculosis in South
      Africa: is it patient-centred?
AB  - To improve the treatment of patients co-infected with multidrug-resistant
      tuberculosis (MDR-TB) and the human immunodeficiency virus, we measured the
      relationship between treatment outcomes and hospital performance at four
      decentralised MDR-TB sites in South Africa. We describe hospital performance from
      the patient's perspective by the use of a graphic that visually represents a
      patient's treatment journey. The graphic was used to report study findings to
      study sites and as a catalyst for a quality improvement process. 

PMID- 24020604
TI  - H2O-EG-assisted synthesis of uniform urchinlike rutile TiO2 with superior lithium
      storage properties.
AB  - A facile green method to synthesize uniform nanostructured urchinlike rutile TiO2
      is demonstrated. Titanium trichloride was selected as the TiO2 precursor, and a
      mixed solvent containing H2O and ethylene glycol was used. By using this binary
      medium, the nucleation and crystal growth of rutile TiO2 can be regulated, giving
      rise to very uniform urchinlike structures with tailorable sizes. As confirmed by
      the SEM and TEM analysis, large particles with dense aggregation of needle-like
      building blocks or small ones with loosely packed subunits could be obtained at
      different reaction conditions. The as-prepared samples were applied as the anode
      material for lithium-ion batteries, and they were shown to have superior
      properties with a high reversible capacity of 140 mA h g(-1) at a high current
      rate of 10 C for up to 300 cycles, which is almost unmatched by other rutile TiO2
      based electrodes. A stable capacity of 88 mA h g(-1) can also be delivered at an
      extremely high rate of 50 C, suggesting the great potential of the as-prepared
      product for high-rate lithium-ion batteries. 

PMID- 24020605
TI  - Rural women's strategic responses to intimate partner violence.
AB  - In this study we explored rural women's (N = 37) perceptions of strategy use and
      effectiveness in dealing with intimate partner violence (IPV). We used all six
      categories of the IPV Strategies Index (Goodman, Dutton, Weinfurt, & Cook, 2003 )
      to assess the strategic responses used by women in the sample and the level of
      helpfulness associated with each strategy. The strategy category used most often
      was resistance, and the category deemed most helpful was safety planning.
      Implications include finding ways for practitioners, advocates, and researchers
      to support and highlight the resourcefulness of rural survivors of IPV residing
      in the United States. 

PMID- 24020606
TI  - Feast day service honoring pioneers in medicine.
AB  - The Standing Liturgical Commission of the Anglican Church in the United States
      has identified persons whom they consider Holy men or Holy women, and who are
      celebrated in Lesser Feast and Fast day services. In 2009, the triennial General
      Convention of the Anglican Church, USA, ratified the recommendation of the
      Commission that Dr. William W. Mayo and Dr. Charles Menninger and their sons, as
      pioneers in medicine, were worthy of such a designation. The author was
      approached to deliver the following homily at a service at the Palmer Memorial
      Episcopal Church in Houston, Texas, March 6, 2013. 

PMID- 24020607
TI  - Religious doubts: implications for psychopathology and psychotherapy.
AB  - This article examines the psychopathological implications of religious doubts.
      Following a discussion of their prevalence, their role in development and causal
      factors, and their impact upon religious belief, the author discusses the
      relationship between religious doubts and anxiety and depression. Religious
      doubts may enter the psychotherapeutic process, and the author discusses one form
      of religious cognitive-behavioral therapy using the Bible that might be useful
      for Christian patients with such doubts. The author presents a case study to
      exemplify these points. 

PMID- 24020608
TI  - A track-based approach for treating eating disorders.
AB  - The authors discuss the development of a track-based approach to working with
      disordered eating patients in an inpatient psychiatric facility. Because of the
      high mortality rate and complex presentation of patients with eating disorders,
      treatment is essential. However, treatment in a specialized eating disorder
      program is not always feasible. The authors present their rationale for creating
      an Eating Disorder Track imbedded in an inpatient facility that offers several
      week lengths of stay conducive to intensive psychotherapeutic and milieu
      treatment.

PMID- 24020609
TI  - Gender as a longitudinal moderator of the relationship between attributional
      style and depressive symptoms over a 1-year period in preadolescent children.
AB  - Depressive symptoms and attributional style were assessed in a sample of 7- to 11
      year-old children at two time points. Findings revealed that boys and girls did
      not differ in their level of depressive symptoms over 1 year. At baseline, boys
      were more likely than girls to make stable attributions for negative events. Boys
      made fewer stable attributions for positive events than did girls. Moderational
      analyses suggested that attributional style more strongly predicted changes in
      the number of depressive symptoms 1 year later in boys when compared to girls.
      Findings emphasize the need to address vulnerability factors in preadolescent
      boys that may put them at risk for the development of later depressive symptoms. 

PMID- 24020610
TI  - Relational trauma: using play therapy to treat a disrupted attachment.
AB  - Caregiver-child attachment results in a cognitive-emotional schema of self,
      other, and self-other relationships. Significantly disrupted attachments may lead
      to pathogenic internal working models, which may have deleterious consequences;
      this indicates the need for early attachment intervention. The authors consider
      the therapy of a 3-year-old boy with aggressive behaviors who had lacked
      consistent caregiving. Attachment theory can account for the child's
      psychotherapeutic gains, despite his insecure attachment style. The authors
      discuss discrepancies between treatment and current research trends. 

PMID- 24020611
TI  - Predicting relatedness and self-definition depressive experiences in aging women
      based on personality traits: a preliminary study.
AB  - As part of the research relating personality and depression, this study seeks to
      predict depressive experiences in aging women according to Sidney Blatt's
      perspective based on the Five-Factor Model of Personality. The NEO-Five Factor
      Inventory and the Depressive Experiences Questionnaire were administered. The
      domains Neuroticism, Agreeableness, and Conscientiousness predicted self
      criticism, explaining 68% of the variance; the domains Neuroticism and
      Extraversion predicted dependency, explaining 62% of the variance. The subfactors
      Neediness and Connectedness were differently related to personality traits. These
      findings are relevant to the research relating personality and anaclitic /
      introjective depressive experiences in late adulthood. 

PMID- 24020614
TI  - Determining the fibrillar orientation of bast fibres with polarized light
      microscopy: the modified Herzog test (red plate test) explained.
AB  - The identification of bast fibre samples, in particular, bast fibres used in
      textiles, is an important issue in archaeology, criminology and other scientific
      fields. One of the characteristic features of bast fibres is their fibrillar
      orientation, referred to as Z- or S twist (or alternatively right- and left
      handed fibres). An empirical test for determining the fibrillar orientation using
      polarized light microscopy has been known in the community for many years. It is
      referred to as the modified Herzog test or red plate test. The test has the
      reputation for never producing false results, but also for occasionally not
      working. However, so far, no proper justification has been provided in the
      literature that the 'no false results' assumption is really correct and it has
      also not been clear up till now, why the method sometimes does not work. In this
      paper, we present an analytical model for the modified Herzog test, which
      explains why the test never gives a false result. We also provide an explanation
      for why the Herzog test sometimes does not work: According to our model, the
      Herzog test will not work if none of the three distinct layers in the secondary
      cell wall is significantly thicker than the others. 

PMID- 24020615
TI  - The role of the crystallization temperature on the nanophase structure evolution
      of poly[(R)-3-hydroxybutyrate].
AB  - The nanophase structure of semicrystalline polymers, which determines the
      mechanical, thermal, and gas permeability behavior, can be quantified by thermal
      methods. A detailed investigation of the nanophase structure of poly[(R)-3
      hydroxybutyrate] (PHB) was performed under conditions of isothermal, quasi
      isothermal, and nonisothermal crystallizations. The experimental analyses
      revealed that the establishment of the nanophase rigid amorphous fraction (RAF)
      in PHB depends on the temperature at which crystallization occurs. The RAF grows
      in parallel with the crystal phase during quasi-isothermal crystallization at 30 
      degrees C, whereas during nonisothermal crystallization at higher temperatures,
      RAF starts to develop at 70  degrees C, in correspondence with the final stages
      of the crystallization process. The influence of crystallization temperature on
      the nanophase structure was rationalized taking into account the effect of the
      mobility of the entangled chain segments during the phase transition. The melting
      behavior was found to change after isothermal crystallization at 70  degrees C,
      revealing that complete RAF mobilization is achieved approximately at this
      temperature. The temperature of 70  degrees C could be the limit for the
      formation and the disappearance of rigid amorphous fraction in the PHB analyzed
      in the present study. 

PMID- 24020613
TI  - Consistent condom use with regular, paying, and casual male partners and
      associated factors among men who have sex with men in Tamil Nadu, India: findings
      from an assessment of a large-scale HIV prevention program.
AB  - BACKGROUND: Men who have sex with men (MSM) are a marginalized population at high
      risk for HIV infection. Promoting consistent condom use (CCU) during anal sex is
      a key risk reduction strategy for HIV prevention among MSM. To inform effective
      HIV prevention interventions, we examined the factors associated with CCU among
      MSM with their regular, paying, and casual partners, as well as with all three
      types of partners combined. METHODS: Data for this analysis were from a large
      scale bio-behavioural survey conducted during 2009-2010 in Tamil Nadu, India. MSM
      aged 18 years or older were recruited for the survey using time-location cluster
      sampling at cruising sites in four districts of Tamil Nadu. Binary logistic
      regression analyses were conducted to assess the association of CCU with selected
      socio-demographic characteristics and other contextual factors. RESULTS: Among
      1618 MSM interviewed, CCU during anal sex with regular, paying, and a casual male
      partner was 45.3%, 50.8% and 57.9%, respectively. CCU with all three types of
      partners combined was 52.6%. Characteristics associated with increased odds for
      CCU with MSM having all three types of partners combined were frequent receptive
      anal sex acts with regular partners (adjusted odds ratio [AOR] 2.17, 95%
      confidence interval [CI] 1.01-4.65), fewer number of casual partners (AOR 3.41,
      95% CI 1.50-7.73) and membership in a community-based organization (CBO) for MSM
      (AOR 3.54, 95% CI 1.62-7.74). CCU with regular partners was associated with
      membership in a CBO (AOR 1.96, 95% CI 1.23-3.11), whereas CCU with paying, and
      casual male partners was associated with perceived higher risk of acquiring HIV
      (AOR 1.92, 95% CI 1.22-3.01) and exposure to any HIV prevention intervention (AOR
      3.62, 95% CI 1.31-10.0), respectively. Being aged 26 years or older, being in
      debt, and alcohol use were factors associated with inconsistent condom use across
      partner types. CONCLUSION: HIV interventions among MSM need to promote CCU with
      all types (regular, paying, and causal) of male partners, and need to reach MSM
      across all age groups. In addition to enhancing interventions that focus on
      individual level risk reduction, it is important to undertake structural
      interventions that promote social acceptance of same-sex sexuality and address
      contextual barriers to condom use such as alcohol use.

PMID- 24020616
TI  - Tibial cancellous bone grafting in jaw reconstruction: 10 years of experience in
      Taiwan.
AB  - BACKGROUND: Use of proximal tibia as a donor site has been applied in jawbone
      reconstruction since the 1990s. Catone and colleagues described a U-shaped
      incision made on the iliotibial tract during tibial cancellous bone procurement
      for maxillofacial reconstruction in 1992. We used a curvilinear incision on the
      iliotibial tract in lateral approach in our tibial cancellous bone harvesting
      procedure. OBJECTIVES: The objectives of this retrospective study are to describe
      our modified lateral approach for procuring cancellous graft from the proximal
      tibia and to assess the bone volume, donor site morbidity, and associated
      complications. MATERIAL AND METHODS: Eighty consecutive jawbone reconstructions
      utilizing autogenous tibial cancellous bone grafts in 78 patients from March 1998
      through March 2008 were reviewed. The patient group consisted of 45 males and 33
      females, ages 18 to 76 (average age 36.1 +/- 12.3). Minimal postoperative follow
      up period was 3 months. Unlike the traditional U-shaped trapdoor incision on the
      iliotibial tract, our curvilinear incision was made almost parallel to the fibers
      of that tract. RESULT: Only mild complications were observed at donor sites,
      including temporary paresthesia, gait disturbance, and an unpleasant scar. The
      average procured graft volume was 17.8 mL. We also present the first case of
      reconstruction of mandibular continuity defects of up to 6 to 7 cm lengthwise by
      tibial cancellous bone grafting, which has not previously been reported in the
      English literature. CONCLUSION: The modified incision on the iliotibial tract
      allowed access to obtain an equally good bone volume from the lateral aspect of
      the proximal tibia, and it rendered wound closure much easier than the procuring
      techniques described in the earlier literature.

PMID- 24020617
TI  - N-heterocyclic carbene-catalyzed stereoselective cascade reaction: synthesis of
      functionalized tetrahydroquinolines.
AB  - The first N-heterocyclic carbene-catalyzed stereoselective aza-Michael-Michael
      lactonization cascade reaction of 2'-aminophenylenones and 2-bromoenals for the
      construction of chiral functionalized tetrahydroquinolines with three consecutive
      stereogenic centers has been achieved in high yields (up to 98%) with excellent
      diastereo- (>25:1) and enantioselectivities (up to 98.7% ee). 

PMID- 24020618
TI  - Health literacy and ethnic disparities in health-related quality of life among
      rural women: results from a Chinese poor minority area.
AB  - BACKGROUND: We examined the relationship between health literacy (HL) and health
      related quality of life (HRQoL) as well as relationship differentials by
      ethnicity among rural women from a Chinese poor minority area. METHODS: We
      conducted in-person interviews with 913 rural women aged 23 - 57 (57.5% Hui
      minorities/42.5% Han ethnicity) enrolled in the Ningxia Women Health Project,
      gathering data on EQ-5D, self-designed HL, socio-demographic characteristics, and
      chronic diseases. The extent of impairments in the five dimensions of the EQ-5D
      was used to measure HRQoL. Factor analysis yielded a single HL factor, which was
      used as a dichotomous variable in multivariate log-binomial regression models
      that examined the adjusted association of HL with HRQoL. RESULTS: Nearly half of
      the women had no formal education. The most prevalent impairments were
      pain/discomfort and anxiety/depression (42.42% and 32.09%, respectively). The Hui
      minorities had 1.65 times higher rates of low HL (defined as less than mean of
      the factor score for HL) and 1.22 and 1.25 times for pain/discomfort and
      anxiety/depression impairments, respectively. Low HL was associated with poor
      HRQoL, with a 23% increase in the prevalence of pain/discomfort impairments after
      adjusting for socio-demographics. This association was significant in the Hui
      group (PR=1.30, 95% CI=1.06-1.58) but not for the Han group (PR=0.99, 95% CI=0.76
      1.30). HL-stratified analysis revealed modification for ethnic disparities in
      HRQoL; for pain/discomfort impairments, high HL-PR=0.88 (95% CI=0.71-1.08), low
      HL-PR=1.24 (95% CI = 1.01-1.52); for anxiety/depression impairments, high HL
      PR=0.98 (95% CI=0.73-1.32), low HL-PR=1.44 (95% CI = 1.05-1.98). CONCLUSIONS: Low
      HL is associated with poor HRQoL across the entire sample and the association may
      be modified by ethnicity. Similarly, ethnic disparities in HRQoL may be modified
      by HL, larger in low HL group. Health services should address HL in vulnerable
      minority women to improve their HRQoL.

PMID- 24020619
TI  - Prevalence of antibodies against Leptospira sp. in snakes, lizards and turtles in
      Slovenia.
AB  - BACKGROUND: Leptospiral infections in poikilothermic (cold blooded) animals have
      received very little attention and the literature concerning natural infections
      of these animals is limited. The aim of this study was to determine the
      prevalence of leptospiral antibodies in reptiles, imported into Slovenia and
      intended to be pets in close contact with humans. A total of 297 reptiles (22
      snakes, 210 lizards and 65 turtles) were tested for specific antibodies against
      serovars of Leptospira interrogans sensu stricto using the microscopic
      agglutination test (MAT). Live cultures of different serovars were used as
      antigens. MAT was performed according to standard procedures and the degree of
      reaction was interpreted by estimating the percentage of agglutinated
      leptospires. Samples showing titres of  >=  50 against one or more serovars were
      considered as positive. RESULTS: Antibodies against seven pathogenic serovars of
      L. interrogans sensu stricto were detected in 46 of 297 reptiles. Among 22
      snakes, specific antibodies against pathogenic serovars of three Leptospira
      species (L. interrogans, L. kirschneri and L. borgpetersenii) at titre levels
      from 1:50 to 1:400 were detected in 6 snakes. In 31 of 210 lizards, specific
      antibodies were found in titres from 1:50 to 1:1000 and, finally, among 65
      turtles (terrapins and tortoises), 9 had specific antibodies at titre levels
      between 1:50 and 1:1600. Animals imported from non-EU countries showed
      significantly higher prevalence (25.0%; 95 confidence interval: 16.7-33.3%) than
      animals from EU member states (10.4%; confidence interval: 6.1-14.7%).
      CONCLUSIONS: Reptiles may be considered as potential reservoirs of L. interrogans
      sensu stricto. Origin of the animals is a risk factor for presence of leptospiral
      antibodies, especially in lizards. Special attention should be focused on animals
      from non-EU member states.

PMID- 24020620
TI  - [Treatment of primary anterior shoulder dislocation; do not always treat
      conservatively].
AB  - According to the current guidelines, primary anterior shoulder dislocations are
      treated conservatively after repositioning by short-term immobilisation of the
      shoulder. Shoulder stabilization surgery--either open or arthroscopically-
      reduces the risk of recurrence and improves the functional outcome over the long
      term. Active young adults are known to have up to a 90% increased risk of
      recurrent dislocation after the conservative treatment of a primary shoulder
      dislocation. Active young men particularly benefit from shoulder stabilization
      surgery. When comparing operative techniques, there is no difference between an
      open procedure and an arthroscopic procedure in terms of recurrence. The choice
      between open treatment and arthroscopic treatment depends on the preference of
      the patient and the experience of the surgeon.

PMID- 24020621
TI  - [Addison's disease, primary adrenal insufficiency in adults].
AB  - Adrenal insufficiency is a rare but fatal disease if left unrecognized. Symptoms
      often mimic more prevalent diseases. We discuss three patients with primary
      adrenal insufficiency. These cases illustrate that presenting symptoms such as
      syncope, nausea, vomiting, weight loss and hypoglycemia are often non-specific
      and, therefore, often not immediately recognized. When an adrenal crisis is
      suspected, glucocorticoids should be given promptly. The symptoms are caused by
      insufficient production of adrenal hormones due to destruction of the adrenal
      glands by auto-immune adrenalitis. An ACTH stimulation test should confirm the
      diagnosis when primary adrenal insufficiency is suspected. Treatment consists of
      glucocorticoid and mineralocorticoid replacement. Primary adrenal insufficiency
      is a 'master of disguise'. Unexplained syncope, vomiting, weight loss or
      hypoglycemia should prompt suspicion of this disease. 

PMID- 24020622
TI  - [10 years after implementation of the Liverpool Care Pathway for the dying
      patient; important improvements in end-of-life care].
AB  - The Liverpool Care Pathway for the dying patient (LCP) is a quality instrument
      that contributes to the quality of care of dying patients. The pathway provides
      care goals for structuring the multidisciplinary care of patients who are in the
      last hours or days of life and their families. The LCP should be used as soon as
      the multidisciplinary team recognises that the patient's death within hours or
      days is imminent. Research has shown that using the pathway contributes to better
      symptom control in the patient and improved coping with grief by relatives, among
      other things. At this time, the Dutch version of the LCP ('Zorgpad Stervensfase')
      has been implemented in over 100 healthcare institutions in the Netherlands. A
      digital version of the LCP is under construction, which makes it possible to
      integrate it in electronic patient files. This digital version will also
      stimulate quality assurance and scientific research. 

PMID- 24020623
TI  - [Nocturnal choking sensation].
AB  - There are many different types of sleep disorders. The majority of sleep-related
      breathing disorders can be attributed to sleep apnoea syndrome. Nocturnal choking
      sensation is a different symptom, for which we present two cases. Nocturnal
      choking sensation is a terrifying symptom for the patient and the diagnostic
      approach can be challenging. Aside from sleep choking syndrome, this symptom may
      appear with nocturnal laryngospasm, insular epilepsy and nocturnal gastro
      oesophageal reflux. A thorough patient history and observation of the nocturnal
      event, sometimes supported by EEG findings, may provide the clue to the
      diagnosis. These kinds of nocturnal symptoms are best analyzed in a clinic
      specialized in both epilepsy and sleep disorders. 

PMID- 24020624
TI  - [Physical activity in wheelchair users with spinal cord injury: prerequisites for
      and effects of an active lifestyle].
AB  - Wheelchair users with spinal cord injury generally have a relatively inactive
      lifestyle. Several studies have shown that an inactive lifestyle is associated
      with a lower fitness level, poorer health, reduced social participation and a
      lower quality of life for wheelchair users. There are a number of ways in which
      wheelchair users can remain active in daily life, for instance, by using a
      wheelchair or handbike for mobility instead of taking the car, and by
      participating in sports or wheelchair sports. Some prerequisites should be met to
      enable wheelchair users to have a more active lifestyle: the wheelchair should be
      optimally adjusted and the everyday environment, including sport facilities,
      should be easily accessible. An active lifestyle often also requires a change in
      attitude or behaviour. General practitioners, other primary healthcare providers
      and rehabilitation professionals can help in this respect.

PMID- 24020625
TI  - [Periaortitis following endovascular aortic repair].
AB  - BACKGROUND: Infection is the most obvious cause of fever following implantation
      of an endovascular prosthesis; however, fever and inflammation around the
      arterial wall can also be caused by a sterile inflammatory reaction:
      periaortitis. CASE STUDY: An 81-year-old man was referred because of fever and
      back pain. He had undergone an endovascular aortic repair (EVAR) 1 year earlier;
      an endovascular prosthesis had been placed during this procedure, to repair an
      abdominal aortic aneurysm. A positive emission tomography (PET)-CT scan revealed
      uptake of 18F-fluorodeoxyglucose around the endovascular prosthesis, consistent
      with infection; however, intensive microbiological investigation, including
      biopsy from the site of the endovascular prosthesis, revealed no micro-organisms.
      Empirical administration of antibiotics had no effect. Decreased renal function
      occurred approximately 4 weeks later, and a CT scan revealed spread of the
      inflammatory process accompanied by hydronephrosis, consistent with periaortitis.
      Following treatment with glucocorticoids, renal function returned to normal and
      the symptoms disappeared. CONCLUSION: Periaortitis is a rare, late complication
      of an EVAR. Clinical presentation can closely resemble an infection, while
      distinguishing infection from (sterile) periaortitis is important for the choice
      of treatment.

PMID- 24020626
TI  - [Rotavirus vaccination: a priority for high-risk children].
AB  - Rotaviruses cause acute gastroenteritis; mostly in young children. Infant
      rotavirus vaccines have been licensed in Europe and provide excellent protection
      against severe gastroenteritis, but are not widely implemented due to the
      perceived benign character of rotavirus disease and unfavourable cost
      effectiveness. Rotavirus vaccines are currently unavailable in the Netherlands
      which leaves a particularly vulnerable group of infants--those with prematurity,
      low birth weight or severe congenital malformations--at increased risk of
      rotavirus disease, complications and even death. Rotavirus vaccination should be
      made available to these infants, but due to the strict age limits for the
      rotavirus vaccination (which must be started at < 14 weeks), vaccination cannot
      be adequately organised within the Dutch National Immunisation Programme (NIP)
      which relies on well-baby clinic visits. Organising rotavirus vaccination for
      high-risk infants through paediatric secondary care could overcome this problem
      and be implemented independent of decisions on uptake of rotavirus vaccination
      within the Dutch NIP.

PMID- 24020628
TI  - Tetragonal phase germanium nanocrystals in lithium ion batteries.
AB  - Various germanium-based nanostructures have recently demonstrated outstanding
      lithium ion storage ability and are being considered as the most promising
      candidates to substitute current carbonaceous anodes of lithium ion batteries.
      However, there is limited understanding of their structure and phase evolution
      during discharge/charge cycles. Furthermore, the theoretical model of lithium
      insertion still remains a challenging issue. Herein, we performed comparative
      studies on the cycle-dependent lithiation/delithiation processes of germanium
      (Ge), germanium sulfide (GeS), and germanium oxide (GeO2) nanocrystals (NCs). We
      synthesized the NCs using a convenient gas phase laser photolysis reaction and
      attained an excellent reversible capacity: 1100-1220 mAh/g after 100 cycles.
      Remarkably, metastable tetragonal (ST12) phase Ge NCs were constantly produced
      upon lithiation and became the dominant phase after a few cycles, completely
      replacing the original phase. The crystalline ST12 phase persisted through 100
      cycles. First-principles calculations on polymorphic lithium-intercalated
      structures proposed that the ST12 phase Ge12Lix structures at x >= 4 become more
      thermodynamically stable than the cubic phase Ge8Lix structures with the same
      stoichiometry. The production and persistence of the ST12 phase can be attributed
      to a stronger binding interaction of the lithium atoms compared to the cubic
      phase, which enhanced the cycling performance. 

PMID- 24020627
TI  - Dexamethasone tachyphylaxis in the treatment of macular oedema.

PMID- 24020629
TI  - LET-painting increases tumour control probability in hypoxic tumours.
AB  - LET-painting was suggested as a method to overcome tumour hypoxia. In vitro
      experiments have demonstrated a well-established relationship between the oxygen
      enhancement ratio (OER) and linear energy transfer (LET), where OER approaches
      unity for high-LET values. However, high-LET radiation also increases the risk
      for side effects in normal tissue. LET-painting attempts to restrict high-LET
      radiation to compartments that are found to be hypoxic, while applying lower LET
      radiation to normoxic tissues. Methods. Carbon-12 and oxygen-16 ion treatment
      plans with four fields and with homogeneous dose in the target volume, are
      applied on an oropharyngeal cancer case with an identified hypoxic entity within
      the tumour. The target dose is optimised to achieve a tumour control probability
      (TCP) of 95% when assuming a fully normoxic tissue. Using the same primary
      particle energy fluence needed for this plan, TCP is recalculated for three cases
      assuming hypoxia: first, redistributing LET to match the hypoxic structure (LET
      painting). Second, plans are recalculated for varying hypoxic tumour volume in
      order to investigate the threshold volume where TCP can be established. Finally,
      a slight dose boost (5-20%) is additionally allowed in the hypoxic subvolume to
      assess its impact on TCP. Results. LET-painting with carbon-12 ions can only
      achieve tumour control for hypoxic subvolumes smaller than 0.5 cm(3). Using
      oxygen-16 ions, tumour control can be achieved for tumours with hypoxic
      subvolumes of up to 1 or 2 cm(3). Tumour control can be achieved for tumours with
      even larger hypoxic subvolumes, if a slight dose boost is allowed in combination
      with LET-painting. Conclusion. Our findings clearly indicate that a substantial
      increase in tumour control can be achieved when applying the LET-painting concept
      using oxygen-16 ions on hypoxic tumours, ideally with a slight dose boost.

PMID- 24020630
TI  - Factors correlating with delayed trauma center admission following traumatic
      brain injury.
AB  - BACKGROUND: Delayed admission to appropriate care has been shown increase
      mortality following traumatic brain injury (TBI). We investigated factors
      associated with delayed admission to a hospital with neurosurgical expertise in a
      cohort of TBI patients in the intensive care unit (ICU). METHODS: A retrospective
      analysis of all TBI patients treated in the ICUs of Helsinki University Central
      Hospital was carried out from 1.1.2009 to 31.12.2010. Patients were categorized
      into two groups: direct admission and delayed admission. Patients in the delayed
      admission group were initially transported to a local hospital without
      neurosurgical expertise before inter-transfer to the designated hospital.
      Multivariate logistic regression was utilized to identify pre-hospital factors
      associated with delayed admission. RESULTS: Of 431 included patients 65% of
      patients were in the direct admission groups and 35% in the delayed admission
      groups (median time to admission 1:07h, IQR 0:52-1:28 vs. 4:06h, IQR 2:53-5:43, p
      <0.001). In multivariate analysis factors increasing the likelihood of delayed
      admission were (OR, 95% CI): male gender (3.82, 1.60-9.13), incident at public
      place compared to home (0.26, 0.11-0.61), high energy trauma (0.05, 0.01-0.28),
      pre-hospital physician consultation (0.15, 0.06-0.39) or presence (0.08, 0.03
      0.22), hypotension (0.09, 0.01-0.93), major extra cranial injury (0.17, 0.05
      0.55), abnormal pupillary light reflex (0.26, 0.09-0.73) and severe alcohol
      intoxication (12.44, 2.14-72.38). A significant larger proportion of patients in
      the delayed admission group required acute craniotomy for mass lesion when
      admitted to the neurosurgical hospital (57%, 21%, p< 0.001). No significant
      difference in 6-month mortality was noted between the groups (p= 0.814).
      CONCLUSION: Delayed trauma center admission following TBI is common. Factors
      increasing likelihood of this were: male gender, incident at public place
      compared to home, low energy trauma, absence of pre-hospital physician
      involvement, stable blood pressure, no major extra cranial injuries, normal
      pupillary light reflex and severe alcohol intoxication. Focused educational
      efforts and access to physician consultation may help expedite access to
      appropriate care in TBI patients.

PMID- 24020631
TI  - Theoretical, antioxidant and cytotoxic activities of caffeic acid phenethyl ester
      and chrysin.
AB  - The structure-activity relationship was used to describe the antioxidant
      pharmacophore of caffeic acid phenethyl ester (CAPE) and chrysin by using quantum
      chemical calculations and the density functional theory method. The Becke three
      parameter hybrid exchange functional in combination with the Lee-Yang-Parr
      correction functional protocol was employed for structure optimization and other
      computations. Theoretical calculations were conducted to explain the structure
      activity relationship and pharmacokinetic behavior of CAPE and chrysin. The free
      radical scavenging activities of CAPE and chrysin were evaluated by using the 2,2
      diphenyl-1-picrylhydrazyl assay. The cytotoxic effects of CAPE and chrysin on the
      human leukemia cell line (HL-60) were evaluated by using the 3-(4,5-dimethyl
      thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

PMID- 24020632
TI  - Splenosystemic shunts in cats: a retrospective of 33 cases (2004-2011).
AB  - BACKGROUND: Portosystemic shunts are uncommonly reported in cats. The majority of
      reports describe congenital shunts in young cats originating from the left
      gastric vein. Although they are only rarely reported, acquired portosystemic
      shunts in cats appear to be more variable in their anatomic location.
      HYPOTHESIS/OBJECTIVE: To describe the signalment and disease conditions found in
      cats with splenosystemic shunts. ANIMALS: Thirty-three client-owned cats with
      documented splenosystemic shunts. MATERIALS AND METHODS: Retrospective study. All
      cats with vascular communications between the splenic and left renal veins or the
      splenic vein and caudal vena cava diagnosed ultrasonographically between 2004 and
      2011 were included. Collected data included age, breed, sex, presenting
      complaints, clinicopathologic data, as well as clinical diagnosis when available.
      RESULTS: Splenosystemic shunts were identified in 1.3% of the cats that had an
      abdominal ultrasound performed during the study period. Older, spayed female cats
      were found to be significantly overrepresented when compared with the total
      population of cats having undergone ultrasound over the same time period. A large
      proportion of cats (42%) had a hepatopathy with the potential for associated
      portal hypertension. CONCLUSIONS AND CLINICAL IMPORTANCE: Neither the signalment
      of cats in this report nor the anatomy of their portovascular anomalies shared
      similarities with those cats previously identified with single-vessel shunts. The
      relevance and etiology of these newly described splenosystemic shunts remain
      elusive and warrantsfurther investigation.

PMID- 24020633
TI  - Openness and avoidance--a longitudinal study of fathers of children with
      intellectual disability.
AB  - BACKGROUND: Fathers' interactions with children who have intellectual
      disabilities (ID) or developmental delays (DD) have increased over the past few
      decades and may be expected to continue to increase as maternal and paternal
      roles, along with other gender roles, become more equal. The aim of the present
      study was to explore fathers' experiences of parenthood in relation to a child
      with ID/DD from the initial discovery of the disability to 5 years later.
      METHODS: Fathers' experiences of parenting children with ID/DD were explored in a
      longitudinal framework. Seven Swedish fathers of young children with ID/DD
      participated in a series of semi-structured interviews from 2005 to 2010, and
      their accounts were subjected to interpretative phenomenological analysis.
      RESULTS: The analysis revealed three themes: (1) An interrupted path - no longer
      taking things for granted, which describes the fathers' reactions to their
      children's diagnosis; (2) Being a good father, which describes the fathers'
      overall perceptions of their parenting of a child with ID/DD; and (3) Dealing
      with the unexpected, which describes fathers' individual ways of integrating,
      managing, and living with the knowledge of their child's disability over the 5
      years during which fathers were interviewed. CONCLUSIONS: Fathers' individual
      paths need to be taken into consideration when offering psychological support to
      families of children with ID/DD.

PMID- 24020634
TI  - Asymptomatic papules and plaques in the scalp.

PMID- 24020636
TI  - Analysis of the activation of acetylcholinesterase by carbon nanoparticles using
      a monolithic immobilized enzyme microreactor: role of the water molecules in the
      active site gorge.
AB  - A biochromatographic system was used to study the direct effect of carbon
      nanoparticles (CNPs) on the acetylcholinesterase (AChE) activity. The AChE enzyme
      was covalently immobilized on a monolithic CIM-disk via its NH2 residues. Our
      results showed an increase in the AChE activity in presence of CNPs. The
      catalytic constant (k(cat)) was increased while the Michaelis constant (K(m)) was
      slightly decreased. This indicated an increase in the enzyme efficiency with
      increase of the substrate affinity to the active site. The thermodynamic data of
      the activation mechanism of the enzyme, i.e. DeltaH* and DeltaS*, showed no
      change in the substrate interaction mechanism with the anionic binding site. The
      increase of the enthalpy (DeltaH*) and the entropy (DeltaS*) with decrease in the
      free energy of activation (Ea) was related to structural conformation change in
      the active site gorge. This affected the stability of water molecules in the
      active site gorge and facilitated water displacement by substrate for entering to
      the active site of the enzyme.

PMID- 24020635
TI  - Incidence of certified need of care in the long-term care insurance system and
      its risk factors in the elderly of Japanese population-based cohorts: the ROAD
      study.
AB  - AIM: To examine the incidence of certified need of care in the national long-term
      care insurance (LTCI) system, and to determine its risk factors in the elderly of
      Japanese population-based cohorts of the Research on Osteoarthritis/Osteoporosis
      Against Disability (ROAD) study. METHODS: Of the 3040 participants in the
      baseline examination of the ROAD study, we enrolled 1773 (699 men, 1074 women)
      aged 65 years or older who were not certified as in need of care level elderly at
      baseline. Participants were followed for incident certification of need of care
      in the LTCI system. Associated factors in the baseline examination with
      occurrence were determined by multivariate Cox proportional hazards regression
      analysis. Muscle dysfunction was defined in accordance with the European Working
      Group on Sarcopenia in Older People algorithm for screening sarcopenia. RESULTS:
      A total of 54 men and 115 women were certified as in need of care level elderly
      during the average 4.0-year follow up. The incidence was 2.0 and 2.5 per 100
      person-years in men and women, respectively. Identified risk factors were region,
      age, body mass index <18.5 or >= 27.5 kg/m(2), grip strength, knee extension
      torque, usual gait speed, chair stand time and muscle dysfunction. CONCLUSIONS:
      Both underweight and obesity, as well as low muscle strength and physical
      ability, are risk factors for certification of need of care. Considering muscle
      dysfunction is a risk factor for occurrence, screened individuals are recommended
      to receive early intervention programs regardless of muscle volume.

PMID- 24020637
TI  - Functional characterization of the c.462delA mutation in the NDUFS4 subunit gene
      of mitochondrial complex I.

PMID- 24020638
TI  - Cytological and molecular characterization of three gametoclones of Citrus
      clementina.
AB  - BACKGROUND: Three gametoclonal plants of Citrus clementina Hort. ex Tan., cv.
      Nules, designated ESP, FRA, and ITA (derived from three labs in Spain, France,
      and Italy, respectively), were selected for cytological and molecular
      characterization in order to elucidate genomic rearrangements provoked by
      haploidization. The study included comparisons of their ploidy, homozygosity,
      genome integrity, and gene dosage, using chromosome counting, flow cytometry, SSR
      marker genotyping, and array-Comparative Genomic Hybridization (array-CGH).
      RESULTS: Chromosome counting and flow cytometry revealed that ESP and FRA were
      haploid, but ITA was tri-haploid. Homozygous patterns, represented by a single
      peak (allele), were observed among the three plants at almost all SSR loci
      distributed across the entire diploid donor genome. Those few loci with extra
      peaks visualized as output from automated sequencing runs, generally low or
      ambiguous, might result from amplicons of paralogous members at the locus, non
      specific sites, or unexpected recombinant alleles. No new alleles were found,
      suggesting the genomes remained stable and intact during gametogenesis and
      regeneration. The integrity of the haploid genome also was supported by array-CGH
      studies, in which genomic profiles were comparable to the diploid control.
      CONCLUSIONS: The presence of few gene hybridization abnormalities, corroborated
      by gene dosage measurements, were hypothetically due to the segregation of
      hemizygous alleles and minor genomic rearrangements occurring during the
      haploidization procedure. In conclusion, these plants that are valuable genetic
      and breeding materials contain completely homozygous and essentially intact
      genomes.

PMID- 24020639
TI  - Enhancing the oxygen permeation rate of Zr(0.84)Y(0.16)O(1.92)
      La(0.8)Sr(0.2)Cr(0.5)Fe(0.5)O(3-delta) dual-phase hollow fiber membrane by
      coating with Ce(0.8)Sm(0.2)O(1.9) nanoparticles.
AB  - Zr0.84Y0.16O1.92-La0.8Sr0.2Cr0.5Fe0.5O3-delta (YSZ-LSCrF) dual-phase composite
      hollow fiber membranes were prepared by a combined phase-inversion and sintering
      method. The shell surface of the hollow fiber membrane was modified with
      Ce0.8Sm0.2O1.9 (SDC) via a drop-coating method. As the rate of oxygen permeation
      of the unmodified membrane is partly controlled by the surface exchange kinetics,
      coating of a porous layer of SDC on the shell side (oxygen reduction side) of the
      hollow fiber membrane was found to improve its oxygen permeability. Rate
      enhancements up to 113 and 48% were observed, yielding a maximum oxygen flux of
      0.32 and 4.53 mL min(-1) cm(-2) under air/helium and air/CO gradients at 950 
      degrees C, respectively. Excess coating of SDC was found to induce significant
      gas phase transport limitations and hence lower the rate of oxygen permeation. A
      model was proposed to calculate the length of triple phase boundaries (TPBs) for
      the coated dual-phase composite membrane and to explain the effect of coating on
      the oxygen permeability. 

PMID- 24020640
TI  - Vitamin D and bone health outcomes in older age.
AB  - The aim of this review is to summarise the evidence linking vitamin D to bone
      health outcomes in older adults. A plethora of scientific evidence globally
      suggests that large proportions of people have vitamin D deficiency and are not
      meeting recommended intakes. Older adults are at particular risk of the
      consequences of vitamin D deficiency owing to a combination of physiological and
      behavioural factors. Epidemiological studies show that low vitamin D status is
      associated with a variety of negative skeletal consequences in older adults
      including osteomalacia, reduced bone mineral density, impaired Ca absorption and
      secondary hyperparathyroidism. There seems to be inconsistent evidence for a
      protective role of vitamin D supplementation alone on bone mass. However, it is
      generally accepted that vitamin D (17.5 MUg/d) in combination with Ca (1200 mg/d)
      reduces bone loss among older white subjects. Evidence for a benefit of vitamin D
      supplementation alone on reducing fracture risk is varied. According to a recent
      Agency for Healthcare Research and Quality review in the USA the evidence base
      shows mixed results for a beneficial effect of vitamin D on decreasing overall
      fracture risk. Limitations such as poor compliance with treatment, incomplete
      assessment of vitamin D status and large drop-out rates however, have been
      highlighted within some studies. In conclusion, it is generally accepted that
      vitamin D in combination with Ca reduces the risk of non-vertebral fractures
      particularly those in institutional care. The lack of data on vitamin D and bone
      health outcomes in certain population groups such as diverse racial groups
      warrants attention.

PMID- 24020641
TI  - Extracellular matrix-mediated differentiation of human embryonic stem cells:
      differentiation to insulin-secreting beta cells.
AB  - Stem cells have tremendous potential for treating various human diseases.
      Protocols have been established to differentiate stem cells into specific
      lineages through the provision of signals in the form of growth factors,
      cytokines, or small molecules. Herein we investigate an alternative strategy for
      directed differentiation of human embryonic stem cells (hESCs)--extracellular
      matrix (ECM) mediated differentiation. Decellularized ECM and conditioned media
      from the appropriate committed cell lines are used to differentiate stem cells to
      the required phenotype. Applying this strategy to differentiate hESCs to
      pancreatic beta cells, we have obtained functional cells that secreted insulin in
      a glucose-responsive manner, and were able to recover normoglycemia in a
      streptozotocin (STZ)-induced diabetic mouse model. ECM-mediated differentiation
      was also demonstrated to be effective for the differentiation of hESCs into
      kidney tubule cells and cardiomyocytes. Gene expression studies suggested the
      involvement of integrins and catenins in the beta cell differentiation process;
      in particular, alpha1, alphav, and beta1 integrins, and beta-catenin showed the
      highest upregulation. To further elucidate the biochemical and mechanical cues
      that have led to effective hESC differentiation to beta cells, we have employed
      an artificial system that allowed for variation of matrix stiffness and
      combination of individual ECM proteins at various ratios. The differentiation
      response of hESCs to the native ECM could be approximated by optimizing this
      system.

PMID- 24020642
TI  - Pd-catalyzed oxidative CH/CH direct coupling of heterocyclic N-oxides.
AB  - A highly efficient protocol for C-H/C-H cross-coupling has been found to occur
      between 2-aryl-1,2,3-triazole N-oxides and pyridine N-oxide derivatives. In
      addition, two homocoupling reactions of 2-substituted 1,2,3-triazole N-oxides and
      some pyridine N-oxide derivatives were developed. A possible pathway of C-H/C-H
      direct coupling is discussed. 

PMID- 24020643
TI  - Bond characterization of a unique thiathiophthene derivative: combined charge
      density study and X-ray absorption spectroscopy.
AB  - Thiathiophthene (TTP), a planar molecule with two fused heterocyclic five
      membered rings and an essentially linear S-S-S bond, is a molecule of great
      interest due to its unique chemical bondings. To elucidate the remarkable bonding
      nature, a combined experimental and theoretical study on the electron density
      distribution of 2,5-dimethyl-3,4-trimethylene-6a-TTP (1) is investigated based on
      a multipole model through high-resolution X-ray diffraction data experimentally
      and on the density functional calculations (DFT) theoretically. In addition, S K
      edge X-ray absorption spectroscopy (XAS) is measured to verify the chemical
      bonding concerning the sulfur atoms. The molecule can be firmly described as 10pi
      electron with aromatic character among the eight atoms, S3C5, of the two fused
      five-membered rings plus three-center four-electron sigma character along the S-S
      S bond. Such bonding description is verified with the calculated XAS spectrum,
      where the pre-edge absorption for transitions from S 1s to pi* and sigma* are
      located. The three-center four-electron S-S-S sigma bond makes the terminal S
      atoms richer in electron density than the central one. 

PMID- 24020644
TI  - Evaluating the role of triborane(7) as catalyst in the pyrolysis of
      tetraborane(10).
AB  - The initial steps in the B4H10 pyrolysis mechanism have been elucidated. The
      mechanism can be divided into three stages: initial formation of B4H8, production
      of volatile boranes with B3H7 acting as a catalyst, and formation of nonvolatile
      products. The first step is B4H10 decomposition to either B4H8/H2 or B3H7/BH3
      where the free energy barrier for the first pathway is 5.6 kcal/mol higher (G4,
      333 K) than the second pathway when transition state theory (TST) is used. When
      variation transition state theory (VTST) is used for formation of B3H7/BH3, the
      two pathways become very similar in free energy with the B4H8/H2 pathway becoming
      favored at G4 by 1.0 kcal/mol at 333 K (33.1 versus 34.1 kcal/mol). The
      experimental activation energy for B4H10 pyrolysis is about 10 kcal/mol lower
      than the calculated barrier for B4H10 -> B4H8 + H2, which indicates that this
      reaction is not the rate-determining step. We suggest that the rate-determining
      step is B4H10 + B3H7 -> B4H8 + H2 + B3H7 where B3H7 acts as a catalyst. The role
      of reactive boron hydrides such as B3H7 and B4H8 as catalysts in the build-up of
      larger boron hydrides may be more common than that previously considered. 

PMID- 24020645
TI  - Technical accuracy of printed surgical templates for guided implant surgery with
      the coDiagnostiX TM software.
AB  - BACKGROUND: Printing of templates for guided surgery represents an alternative to
      laboratory manufactured templates. PURPOSE: To determine the technical accuracy
      of a virtually designed and printed surgical template for guided implant surgery
      based on a surface scan of a cast model using the coDiagnostiXTM software.
      MATERIALS AND METHODS: Cast models and the virtual planning data of nine patients
      receiving guided implant surgery with the coDiagnostiX software were analyzed.
      The original cast models were equipped with three titanium pins and scanned with
      a three-dimensional scanner. The scans were uploaded in the coDiagnostiX software
      and the virtual surgical templates were designed including the sleeves at their
      original positions. After printing the surgical templates, the sleeve positions
      were determined by optical scanning, and deviations were calculated and compared
      with the virtual positions of the sleeves. RESULTS: The sleeves showed a mean
      three-dimensional deviation of 0.22 mm (range: 0.07-0.38 mm) in the center of the
      sleeve top, 0.24 mm (range: 0.08-0.36 mm) in the center of the sleeve bases and a
      mean angular deviation of 1.5 degrees  (range: 0.4 degrees -3.3 degrees )
      compared with the virtual positions. CONCLUSIONS: A high accuracy can be achieved
      using printed templates for guided implant surgery, by taking into account all
      sources of inaccuracies.

PMID- 24020646
TI  - Occurrence of multi-oocyte follicles in aquaporin 8-deficient mice.
AB  - BACKGROUND: Granulosa cells play a key role in folliculogenesis and female
      reproduction. Our previous study demonstrated that water channel aquaporin-8
      (AQP8) is expressed in mouse follicular granulosa cells and is an important
      determinant of granulosa cell apoptosis and follicular maturation. More roles of
      AQP8 in folliculogenesis remain to be determined. FINDINGS: The present study
      reports the increased occurrence of multi-oocyte follicles (MOFs) in ovaries of
      AQP8 knockout mice. The MOFs in AQP8-deficient ovaries contained two or three
      oocytes, and distributed at various follicle stages including primary (12.5%),
      secondary (50%), antral (18.8%) and atretic (18.8%) follicles in 5-week ovaries.
      The MOF is occasionally seen in wild-type ovary only in primary and secondary
      follicles. The number of MOFs in AQP8-deficient ovary reduced with age (26.7 +/-
      5.2 per ovary at 5 weeks old, 14 +/- 5.5 at 10 weeks old, and 3.3 +/- 5.1 at 20
      weeks old). mRNA expression of AQP5, AQP7, AQP8, AQP11 and AQP12 was detected in
      neonatal mouse ovaries and in granulosa cells in 4 week old mouse ovaries. The
      expression of AQP7, AQP11 and AQP12 mRNAs are decreased significantly in neonatal
      AQP8-deficient ovaries, whereas AQP5 mRNA expression remains unchanged.
      CONCLUSIONS: The emergence of MOFs is associated with AQP8 deficiency. The study
      suggested the involvement of AQP8 in the formation of follicles and provided new
      insight into the molecular mechanisms of folliculogenesis.

PMID- 24020647
TI  - Influence of a microbial phytase on the performance and the utilisation of
      energy, crude protein and fatty acids of young broilers fed on phosphorus
      adequate maize- and wheat-based diets.
AB  - 1. The effects of microbial phytase on the performance and nutrient utilisation
      in broilers fed on phosphorus-adequate starter diets were examined in this study.
      The effect of phytase on the apparent ileal digestibility of fatty acids was of
      particular interest. Two grain types (maize and wheat) and two inclusion
      concentrations of a phytase enzyme from Escherichia coli expressed in
      Schizosaccaromyces pombe (0 or 500 phytase units (FTU)/kg of feed) were evaluated
      in a 2 * 2 factorial arrangement of treatments. 2. Supplemental phytase improved
      the weight gain and feed per gain, but had no effect on the feed intake of young
      broilers receiving phosphorus-adequate diets. 3. Phytase supplementation improved
      the apparent ileal digestibility of nitrogen and phosphorus in both diet types.
      Phytase supplementation tended to improve the apparent ileal digestible energy in
      wheat-based diets, but had no effect on the apparent metabolisable energy in both
      diet types. 4. Supplementation of phytase increased the apparent ileal
      digestibility of fat, with similar effects for the different fatty acids
      measured. Increments on ileal fat digestibility due to phytase were not dependent
      on the type of diet. 5. Dietary supplementation of microbial phytase enhanced not
      only the digestibility of phosphorus, but also that of nitrogen and fat,
      exhibiting increased ileal digestibility for all fatty acids in P-adequate maize-
      and wheat-based diets.

PMID- 24020648
TI  - Triplex blue-shifting hydrogen bonds of ClO4(-)...H-C in the nanointerlayer of
      montmorillonite complexed with cetyltrimethylammonium cation from hydrophilic to
      hydrophobic properties.
AB  - In this study, molecular interactions of perchlorate (ClO4(-)), an emerging
      pollutant, with cetyltrimethylammonium(CTMA(+)) complexed in the nanointerlayer
      of negatively charged montmorillonite were characterized using the zeta
      potentials, FTIR, Raman, and XRD spectroscopy and quantified using quantum
      mechanical calculations and sorption experiments. We found that blue-shifting
      hydrogen bonds assisted in the uptake of ClO4(-) from water into the
      nanointerlayer spacing of CTMA(+)-montmorillonite and were tunable according to
      CTMA(+) loading. FTIR spectra presented an obvious 47 cm(-1) blue shift in the C
      H vibration coming from the N-terminal methyl group of CTMA(+) when ClO4(-) was
      absorbed. Quantum mechanical calculations based on density functional theory
      demonstrated that triplex blue-shifting hydrogen bonds of C-H...O were formed
      between the three terminal methyl groups of CTMA(+) and three oxygen atoms of
      ClO4(-). The contribution of blue-shifting hydrogen bonds to perchlorate uptake
      switched from a ClO4(-)/CTMA(+) ratio of 0.0453 at low CTMA(+) loadings to a
      ClO4(-)/CTMA(+) ratio of 0.2563 (5.6-fold) at high CTMA(+) loadings, which can be
      ascribed to the evolution of the nanointerlayer microenvironments from
      hydrophilic properties to hydrophobic properties. The blue-shifting hydrogen bond
      of C-H...O that is tunable with the hydrophobic nature of the organic phase
      should be recognized to elucidate the biochemical behavior of perchlorate in
      organisms. 

PMID- 24020649
TI  - Administration of isoproterenol and adenosine to guide supplemental ablation
      after pulmonary vein antrum isolation.
AB  - BACKGROUND: Pulmonary vein antrum isolation (PVAI) remains associated with atrial
      fibrillation (AF) recurrence. We administered adenosine and isoproterenol (ISP)
      after PVAI to uncover non-PV atrial triggers and PV reconnection, potentially
      increasing ablation success rate. METHODS: One hundred and ninety-two consecutive
      patients with symptomatic AF presenting for PVAI were prospectively studied
      (group 1). Following PVAI, adenosine (18-24 mg) and ISP (20-30 mcg/min) were
      administered intravenously. Supplemental ablation was performed in patients with
      non-PV triggers that induced AF (group 1A). Other subgroups included patients
      with (group 1B) or without (group 1C) consistent non-PV atrial foci that did not
      induce AF. A cohort of 196 matched control patients undergoing PVAI without drug
      challenge was used for comparison (group 2). RESULTS: A total of 132 atrial non
      PV foci were revealed (31 inducing AF). The majority of atrial foci were observed
      with ISP (113/132, 86%). Less than 5% of patients had persistent PV recovery
      during the drug challenge. During a mean follow-up of 22 +/- 8 months, PVAI was
      successful in 110/192 (57%, group 1) versus 100/196 (52%, group 2), P = 0.038.
      Furthermore, the success rate was statistically different between group 1A
      (25/32, 78%), group 1B (28/83, 34%), and group 1C (57/74, 74%), P < 0.001.
      CONCLUSION: After PVAI, ablation guided by the administration of adenosine and
      ISP to target non-PV triggers inducing AF increased AF ablation outcomes.
      Patients with non-PV foci that did not induce AF had no further ablation, with
      the lowest ablation success rate. This group may likely benefit from further
      ablation after PVAI.

PMID- 24020650
TI  - Particle shape anisotropy in pickering emulsions: cubes and peanuts.
AB  - We have investigated the effect of particle shape in Pickering emulsions by
      employing, for the first time, cubic and peanut-shaped particles. The interfacial
      packing and orientation of anisotropic microparticles are revealed at the single
      particle level by direct microscopy observations. The uniform anisotropic
      hematite microparticles adsorb irreversibly at the oil-water interface in
      monolayers and form solid-stabilized o/w emulsions via the process of limited
      coalescence. Emulsions were stable against further coalescence for at least 1
      year. We found that cubes assembled at the interface in monolayers with a packing
      intermediate between hexagonal and cubic and average packing densities of up to
      90%. Local domains displayed densities even higher than theoretically achievable
      for spheres. Cubes exclusively orient parallel with one of their flat sides at
      the oil-water interface, whereas peanuts preferentially attach parallel with
      their long side. Those peanut-shaped microparticles assemble in locally ordered,
      interfacial particle stacks that may interlock. Indications for long-range
      capillary interactions were not found, and we hypothesize that this is related to
      the observed stable orientations of cubes and peanuts that marginalize
      deformations of the interface. 

PMID- 24020651
TI  - Inequality in dental caries distribution at noncavitated and cavitated thresholds
      in preschool children.
AB  - OBJECTIVE: To evaluate the inequality in dental caries distribution according to
      different thresholds assessed using the International Caries Detection and
      Assessment System (ICDAS) and to investigate the associations of socioeconomic
      factors with caries lesions at both noncavitated and cavitated thresholds.
      METHODS: Study subjects were recruited in Santa Maria, Brazil, during the
      National Day of Children's Vaccination, and 639 children aged 12-59 months were
      included. Fifteen calibrated examiners performed the examinations using ICDAS
      criteria. Inequality in dental caries distribution was measured using the Gini
      coefficient, and the Significant Caries Index was calculated for several
      thresholds of ICDAS. Poisson regression analysis was used to assess the
      associations of socioeconomic factors with the highest caries scores. RESULTS:
      The inequality in the distribution of dental caries was lower when precavitated
      caries were included; the Gini coefficient decreased from 0.77 to 0.60 when
      noncavitated caries lesions were included in the analyses. Moreover, the
      inequalities were higher in the younger than in the older children for all
      thresholds. Socioeconomic factors were significantly (P < 0.001) associated with
      caries when an ICDAS score of 3 was considered as the cut-off point. Children
      whose mothers did not complete primary education (P < 0.001) and those with low
      household income (P < 0.001) were more likely to have increased dental caries.
      CONCLUSION: Caries lesions were more equally distributed when noncavitated
      lesions were included in the dental survey. Socioeconomic factors are found to be
      associated with the inequalities in caries distribution in this age group.

PMID- 24020652
TI  - Masitinib-associated minimal change disease with acute tubular necrosis resulting
      in acute kidney injury in a dog.

PMID- 24020654
TI  - Plasmonic band structure controls single-molecule fluorescence.
AB  - Plasmonics and photonic crystals are two complementary approaches to tailor
      single-emitter fluorescence, using strong local field enhancements near metals on
      one hand and spatially extended photonic band structure effects on the other
      hand. Here, we explore the emergence of spontaneous emission control by finite
      sized hexagonal arrays of nanoapertures milled in gold film. We demonstrate that
      already small lattices enable highly directional and enhanced emission from
      single fluorescent molecules in the central aperture. Even for clusters just four
      unit cells across, the directionality is set by the plasmonic crystal band
      structure, as confirmed by full-wave numerical simulations. This realization of
      plasmonic phase array antennas driven by single quantum emitters opens a flexible
      toolbox to engineer fluorescence and its detection. 

PMID- 24020653
TI  - Endophthalmitis and severe blebitis following trabeculectomy. Epidemiology and
      risk factors; a single-centre retrospective study.
AB  - PURPOSE: To study the epidemiology and risk factors of early- and late-onset
      postoperative endophthalmitis (PE) and severe blebitis following trabeculectomy.
      METHODS: Retrospective, single-centre, observational study with a case-control
      design in part. Patients sustaining PE and severe blebitis following
      trabeculectomy or a combined trabeculectomy with a cataract extraction procedure
      performed from 1990 through 2008 and diagnosed from 1990 through 2012 were
      recorded at St Erik Eye Hospital. Incidence data were calculated with help from
      the hospital records. Notes data of cases and of six randomly selected but
      procedure matched control patients for each case were compared. RESULTS: The
      joint rate of infection was 0.46% or 34 incidents in 7402 procedures. The
      frequency of early (occurring <6 weeks after surgery) onset PE was 0.19%, late PE
      was 0.19% and severe blebitis was 0.08%. Dominating aetiologies were
      staphylococci and streptococci. Overall, the infection severely impaired the
      visual function. Combined cataract and fistulating operations were less prone to
      develop late infections, p = 0.04, but no other decisive factors were identified
      in the case-control study. Data collection for all trabeculectomy surgeries from
      1998 and onward identified an increased rate for late infection with the use of
      mitomycin C (MMC), 8 in 1171 surgeries or 0.7%, versus no such use, 0 case of
      late PE in 2136 surgeries, p < 0.001. CONCLUSIONS: Postoperative endophthalmitis
      is a devastating complication after trabeculectomy. The use of MMC increases the
      risk for delayed infection. Early PE after trabeculectomy is clearly more common
      than PE after cataract surgery. Developing efficacious prophylactic antibiotic
      regimens to reduce early PE after penetrating filtering procedures should be a
      major priority in ophthalmic surgery.

PMID- 24020655
TI  - Mental health and PTSD in female North Korean refugees.
AB  - This study was conducted to identify mental health status, post-traumatic stress
      disorder (PTSD), and psychophysiological change in female North Korean refugees.
      Data were collected using questionnaires and symptom checklists that measured
      PTSD and the psychosomatic state of the subjects. As many as 97 subjects, who had
      settled in and around Seoul, South Korea, were selected by snowball sampling.
      Mental health and PTSD levels of the participants were above a moderate level. We
      conclude that health care professionals need to provide female North Korean
      defectors with services to improve mental health and make the sociocultural
      transition successfully. 

PMID- 24020656
TI  - Catheter ablation versus rate control for atrial fibrillation: what have we
      learnt from the ARC-HF trial?

PMID- 24020657
TI  - High blood pressure: can we do better in the future?

PMID- 24020660
TI  - Invasive versus noninvasive cooling after in- and out-of-hospital cardiac arrest.
AB  - Pittl U, Schratter A, Desch S et al. Invasive versus non-invasive cooling after
      in- and out-of-hospital cardiac arrest: a randomized trial. Clin. Res. Cardiol.
      102(8), 607-614 (2013). Therapeutic hypothermia is the cornerstone of the
      postcardiac arrest period management. Several methods may be used as external or
      internal cooling. Pittl et al. reported a randomized, prospective, single-center
      study evaluating an invasive (Coolgard((r))) versus a non-invasive (Arctic
      Sun((r))) cooling method after cardiac arrest in 80 patients in Germany. The
      neurological outcome and neuron-specific enolase level were not different in the
      two groups at 72 h after cardiac arrest. The efficacy of the two cooling methods
      were similar. This study underlines the fact that the type of cooling method is
      not the most important thing to consider in therapeutic hypothermia, but the need
      of a progressive and soft rewarming may make the difference in the future between
      different devices.

PMID- 24020661
TI  - Anti-inflammatory and anti-atherogenic role of BMP receptor II in
      atherosclerosis.
AB  - Evaluation of: Kim CW, Song H, Kumar S et al. Anti-inflammatory and anti
      atherogenic role of BMP receptor II in endothelial cells. Arterioscler. Thromb.
      Vasc. Biol. 33, 1350-1359 (2013). Increased expression of BMPs in atherosclerosis
      suggested that the knockdown of the receptor mediating BMP action would prevent
      endothelial inflammation and atherosclerosis. Based on this hypothesis, Kim et
      al. performed a series of experiments in which the effect of BMP receptor type II
      (BMPRII) knockout was tested in in vitro and in vivo models of atherogenesis.
      Unexpectedly, they found that the loss of BMPRII induces endothelial inflammation
      and atherosclerosis. Knockdown of BMPRII in endothelial cells induced monocyte
      adhesion through the expression of ICAM-1 and VCAM-1. The loss of BMPRII induced
      endothelial inflammation and atherosclerosis in apoE-deficient mice. Besides,
      BMPRII expression was gradually lost over the course of atherosclerosis
      progression in human coronary arteries.

PMID- 24020662
TI  - Highlights of the annual meeting of the Association for European Paediatric and
      Congenital Cardiology.
AB  - The 47th annual meeting of the Association for European Paediatric and Congenital
      Cardiology was held on 22-25th May 2013 in London, UK. This is one of the largest
      scientific meetings in Europe within the field of congenital cardiac disease and
      was held in association with the Japanese Society of Pediatric Cardiology and
      Cardiac Surgery, and Asia Pacific Pediatric Cardiology Society. There were 900
      submitted abstracts and over 1000 delegates from 57 countries attended. We have
      summarized some of the highlights of the meeting below.

PMID- 24020663
TI  - Heart failure therapy: drugs, genes or stem cells?: by Caroline Telfer.
AB  - Professor Sian Harding talks to Caroline Telfer, Assistant Commissioning Editor.
      Professor Sian Harding obtained her PhD in Pharmacology from King's College,
      London (UK) in 1981. She became Professor of Cardiac Pharmacology at the National
      Heart and Lung Institute, a division of the Imperial College Faculty of Medicine,
      in 2002. Her work has been funded by the British Heart Foundation, the Wellcome
      Trust, the Medical Research Council, the Biochemical and Biophysical Research
      Council, the The National Centre for the Replacement, Refinement and Reduction of
      Animals in Research, Pfizer, GlaxoSmithKline and SmithKline Beecham. Harding is
      former president of the European Section of the International Society for Heart
      Research and has organized international cardiovascular science meetings for this
      society, as well as for the European Society of Cardiology. She is the principal
      investigator for the first UK gene therapy trial aimed at improving cardiac
      contractility, organized jointly at Harefield and Papworth Hospitals. Harding is
      a member of the Nuffield Council on Bioethics and the Medical Research Coucil
      Regenerative Medicine Research Committee, and Director of a recently awarded
      British Heart Foundation Cardiovascular Regenerative Medicine Centre. She has
      been elected Fellow of the American Heart Association, European Society of
      Cardiology, International Society for Heart Research, Society of Biology and
      British Society of Pharmacology.

PMID- 24020664
TI  - Psychocardiology: moving toward a new subspecialty.

PMID- 24020665
TI  - Very long stent technology: clinical and practical value.

PMID- 24020666
TI  - Inflatable external leg compression prevents orthostatic hypotension in a patient
      with a traumatic cervical spinal cord injury.
AB  - High thoracic spine or cervical injury may cause long-term orthostatic
      hypotension (OH). To stabilize hemodynamics and prevent presyncope symptoms in
      these patients, noninvasive management is preferable. We describe a case of a 61
      year-old man who experienced presyncope symptoms as a result of severe OH due to
      spinal cord injury, after 60 degrees  head-up tilt position. The patient was
      referred to the intensive care unit where he was successfully managed with an
      inflatable external leg compression (ELC). Accordingly, inflatable ELC succeeded
      not only in improving presyncope symptoms, but also in preventing orthostatic
      hypotension for several hours. ELC may be an alternative way to stabilize
      hemodynamics and prevent presyncope symptoms in patients with OH following spinal
      cord injury.

PMID- 24020667
TI  - Inflatable external upper and lower leg compression improves stroke volume and
      peripheral perfusion during central hypovolemia in healthy volunteers.
AB  - AIM: To determine whether external leg compression (ELC) around the legs could
      prevent and restore central hypovolemia induced by head-up tilt (HUT) maneuver.
      MATERIALS & METHODS: The dynamic effect of ELC was determined using 50 cm H2O
      inflation pressure. HUT was performed without ELC (control model), with ELC
      inflated before HUT (prevention model) and after HUT (restore model). RESULTS:
      The decrease in stroke volume (SV) during the prevention model versus control
      model was 17 +/- 3% versus 27 +/- 3%. The restore model increased SV by 24 +/-
      2%. Similarly, peripheral perfusion measured by perfusion index (PI) and tissue
      oxygen saturation (STO2) was smaller in the prevention model than in the control
      model (PI: 65 +/- 3% vs 79 +/- 2%; STO2: 4 +/- 1% vs 9 +/- 1%). In the restore
      model, PI increased by 117 +/- 24% and STO2 increased by 3 +/- 1%. CONCLUSION: In
      this study, inflatable ELC around the legs was able to prevent and restore SV and
      peripheral perfusion in a model of acute central hypovolemia.

PMID- 24020668
TI  - What can we learn about valvular heart disease from PET/CT?
AB  - Valvular heart disease is a major cause of morbidity and mortality, and with an
      aging population, its prevalence is increasing. Here, we review the evolving use
      of positron emission tomography/computed tomography in valvular heart disease,
      with particular focus on calcific aortic stenosis and infective endocarditis. In
      principle, the activity of any pathological process can be studied, as long as an
      appropriate radiotracer can be developed. We will review some of the early data
      using established tracers in the above and other conditions, providing discussion
      as to the future research and clinical roles of these techniques. Furthermore, we
      will discuss the potential impact of novel tracers that are currently under
      development or testing in preclinical models. It is hoped that such advanced
      imaging might improve the diagnosis, treatment and outlook for patients with
      valvular heart disease. 

PMID- 24020669
TI  - Diagnosis and management of hypotension in neonates.
AB  - The diagnosis and management of hypotension in neonates is a frequently
      encountered issue in the intensive care setting. There is an ongoing debate as to
      the appropriateness of blood pressure monitoring as an indicator of organ
      perfusion and tissue hypoxia. These ultimately determine morbidity and mortality
      in the sick newborn. This article explores the methods available for the
      assessment of organ perfusion and speculates on other means that may become
      available in the future. Different modalities of treatment currently in use are
      discussed, with the aim of using information gained from perfusion monitoring
      techniques to determine the optimal choice of therapy. 

PMID- 24020671
TI  - Advances of cardiovascular MRI in hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by abnormal
      myocardial hypertrophy, which can lead to a wide clinical spectrum, including
      sudden cardiac death and heart failure. Cardiac MRI has a significant role in
      establishing the diagnosis of HCM. In the three principal management issues
      related to HCM; testing of family members of affected individuals; assessing the
      risk of sudden cardiac death from lethal ventricular arrhythmias; and selection
      of appropriate treatments for left ventricular outflow obstruction, cardiac MRI
      has established or emerging roles. 

PMID- 24020672
TI  - Pathophysiology of diastolic dysfunction in chronic heart failure.
AB  - Chronic heart failure is a disease with high morbidity and mortality, and its
      incidence is increasing rapidly worldwide. New therapies are needed that can halt
      or even reverse the progression of heart failure, but little progress has been
      made in the last 20 years. This is partly due to the fact that chronic heart
      failure is a heterogeneous disease with many different etiologies and clinical
      phenotypes. At present, a pathophysiological concept to unify these different
      phenotypes is missing. A prominent pathophysiological feature of chronic heart
      failure is diastolic dysfunction, which is almost universally present in heart
      failure patients. This review will examine the role and mechanisms of diastolic
      dysfunction in heart failure. We will study diastolic dysfunction at different
      levels of complexity of organization: the cardiovascular system, the heart as an
      organ, the myocardium as a tissue, the myocyte as a cell and the molecular
      aspects of diastolic dysfunction. 

PMID- 24020670
TI  - Advances in stress cardiac MRI and computed tomography.
AB  - Stress cardiac MRI and stress computed tomography (CT) perfusion are relatively
      new, noninvasive cardiovascular stress-testing modalities. Both of these tests
      have undergone rapid technical improvements. Data from randomized controlled
      trials in stress cardiac MRI are becoming gradually incorporated into
      cardiovascular clinical practice, not only to assess physiological significance
      of coronary artery disease, but also to provide prognostic information. As CT
      perfusion protocols become more uniform with adequate handling of artifacts and
      decreasing radiation exposure with combined CT coronary angiography/CT perfusion
      imaging, it has the potential to become a comprehensive diagnostic test. 

PMID- 24020673
TI  - In-stent restenosis of drug-eluting stents.
AB  - Drug-eluting stents (DES) have emerged as an improved alternative to bare-metal
      stents by demonstrating reduced rates of restenosis and target lesion
      revascularization. This emergence has led to the unrestricted use of DES for
      various indications and lesions, and subsequently revealed DES in-stent
      restenosis as a novel interventional therapeutic dilemma. Recent insights
      regarding the patho-physiological processes and therapeutic alternatives have
      added to the accumulated knowledge regarding the appropriate approach to this
      phenomenon. This review aims to detail the mechanism and clinical presentation
      of, and therapeutic strategies for, the treatment of DES in in-stent restenosis. 

PMID- 24020674
TI  - An update on complications associated with transcatheter aortic valve
      implantation: stroke, paravalvular leak, atrioventricular block and perforation.
AB  - Transcatheter aortic valve implantation (TAVI) has become an alternative
      therapeutic option for patients with symptomatic severe aortic stenosis at high
      surgical risk and the standard of care in patients who are inoperable for open
      aortic valve replacement. With technological evolution and increasing experience,
      the procedure has become more predictable. Complications of TAVI, however, are
      not infrequent, and can range from minor to life-threatening events. Stroke,
      paravalvular leak, various forms of atrioventricular block, including the need
      for permanent pacemakers and aortic annular and ventricular perforation will be
      the focus of the present review. Other complications associated with TAVI (such
      as vascular injury, acute kidney injury, coronary obstruction, valve
      malpositioning or migration) are clinically important, but are beyond the scope
      of this article. Understanding the occurrence and pathophysiology of these
      complications may provide insights into the improvement of the transcatheter
      devices and techniques, and aid in extending the application of TAVI to a broader
      population. 

PMID- 24020676
TI  - Seminal plasma did not influence the presence of transforming growth factor
      beta1, interleukine-10 and interleukin-6 in porcine follicles shortly after
      insemination.
AB  - BACKGROUND: The effects of seminal plasma on the presence of the cytokines
      transforming growth factor (TGF)-beta1, interleukin (IL)-10 and IL-6 in ovarian
      follicles and follicular fluid were studied shortly after insemination in
      gilts.Ovaries from gilts were sampled 5-6 h after insemination with either
      seminal plasma (SP), fresh semen in extender (Beltsville thawing solution, BTS),
      spermatozoa in extender (Spz), or only BTS (control). RESULTS:
      Immunohistochemical (IHC) labeling of TGF-beta1, IL-10 and IL-6 was evident in
      the ovarian oocytes and granulosa cells independent of stage of follicular
      development (antral follicles). Theca interna cells were labeled to a high degree
      in mature follicles. No consistent differences between treatment groups could be
      observed for any of the cytokines.In follicular fluid, high concentrations of TGF
      beta1 were found while the levels of IL-10 and IL-6 were low. There were no
      differences between treatment groups. CONCLUSIONS: Our results show a presence of
      the cytokines TGF-beta1, IL-6 and IL-10 in oocytes, granulosa and theca cells, as
      well as in the fluid of mature follicles suggesting a role of these cytokines in
      intra-ovarian cell communication. However, treatment (SP, fresh semen in BTS,
      spermatozoa in BTS or BTS) did not influence the IHC-labeling pattern or the
      levels of these cytokines in follicular fluid shortly after insemination.

PMID- 24020677
TI  - Associations between psychological stress, eating, physical activity, sedentary
      behaviours and body weight among women: a longitudinal study.
AB  - BACKGROUND: There is an increased risk of obesity amongst socioeconomically
      disadvantaged populations and emerging evidence suggests that psychological
      stress may be a key factor in this relationship. This paper reports the results
      of cross-sectional and longitudinal analyses of relationships between perceived
      stress, weight and weight-related behaviours in a cohort of socioeconomically
      disadvantaged women. METHODS: This study used baseline and follow-up self-report
      survey data from the Resilience for Eating and Activity Despite Inequality study,
      comprising a cohort of 1382 women aged 18 to 46 years from 80 of the most
      socioeconomically disadvantaged neighbourhoods in Victoria, Australia. Women
      reported their height (baseline only), weight, sociodemographic characteristics,
      perceived stress, leisure-time physical activity, sedentary and dietary
      behaviours at baseline and three-year follow-up. Linear and multinomial logistic
      regression were used to examine cross-sectional and longitudinal associations
      between stress (predictor) and weight, and weight-related behaviours. RESULTS:
      Higher perceived stress in women was associated with a higher BMI, and to
      increased odds of being obese in cross-sectional and longitudinal analyses. Cross
      sectional and longitudinal associations were found between stress and both less
      leisure-time physical activity, and more frequent fast food consumption.
      Longitudinal associations were also found between stress and increased television
      viewing time. CONCLUSION: The present study contributes to the literature related
      to the effects of stress on weight and weight-related behaviours. The findings
      suggest that higher stress levels could contribute to obesity risk in women.
      Further research is needed to fully understand the mechanisms underlying these
      associations. However, interventions that incorporate stress management
      techniques might help to prevent rising obesity rates among socioeconomically
      disadvantaged women.

PMID- 24020678
TI  - Phylogenetic and structural response of heterotrophic bacteria to dissolved
      organic matter of different chemical composition in a continuous culture study.
AB  - Dissolved organic matter (DOM) and heterotrophic bacteria are highly diverse
      components of the ocean system, and their interactions are key in regulating the
      biogeochemical cycles of major elements. How chemical and phylogenetic diversity
      are linked remains largely unexplored to date. To investigate interactions
      between bacterial diversity and DOM, we followed the response of natural
      bacterial communities to two sources of phytoplankton-derived DOM over six
      bacterial generation times in continuous cultures. Analyses of total hydrolysable
      neutral sugars and amino acids, and ultrahigh resolution mass spectrometry
      revealed large differences in the chemical composition of the two DOM sources.
      According to 454 pyrosequences of 16S ribosomal ribonucleic acid genes, diatom
      derived DOM sustained higher levels of bacterial richness, evenness and
      phylogenetic diversity than cyanobacteria-derived DOM. These distinct community
      structures were, however, not associated with specific taxa. Grazing pressure
      affected bacterial community composition without changing the overall pattern of
      bacterial diversity levels set by DOM. Our results demonstrate that resource
      composition can shape several facets of bacterial diversity without influencing
      the phylogenetic composition of bacterial communities, suggesting functional
      redundancy at different taxonomic levels for the degradation of phytoplankton
      derived DOM. 

PMID- 24020679
TI  - Methotrexate treatment of FraX fibroblasts results in FMR1 transcription but not
      in detectable FMR1 protein levels.
AB  - BACKGROUND: Fragile X syndrome is caused by the loss of FMRP expression due to
      methylation of the FMR1 promoter. Treatment of fragile X syndrome patients'
      lymphoblastoid cells with 5-azadeoxycytidine results in demethylation of the
      promoter and reactivation of the gene. The aim of the study was to analyze if
      methotrexate, an agent which also reduces DNA methylation but with less toxicity
      than 5-azadeoxycytidine, has therapeutic potential in fragile X syndrome.
      METHODS: Fibroblasts of fragile X syndrome patients were treated with
      methotrexate in concentrations ranging from 1 to 4 MUg/ml for up to 14 days. FMR1
      and FMRP expression were analyzed by quantitative PCR and western blotting.
      RESULTS: FMR1 mRNA was detected and levels correlated positively with
      methotrexate concentrations and time of treatment, but western blotting did not
      show detectable FMRP levels. CONCLUSIONS: We show that it is possible to
      reactivate FMR1 transcription in fibroblasts of fragile X syndrome patients by
      treatment with methotrexate. However, we were not able to show FMRP expression,
      possibly due to the reduced translation efficacy caused by the triplet repeat
      extension. Unless FMR1 reactivation is more effective in vivo our results
      indicate that methotrexate has no role in the treatment of fragile X syndrome.

PMID- 24020680
TI  - A prospective examination of asthma symptom monitoring: provider, caregiver and
      pediatric patient influences on peak flow meter use.
AB  - OBJECTIVE: This study examined whether provider, caregiver and child
      communication predicted peak flow meter (PFM) use one month later. METHODS: Five
      practices, 35 providers and 296 children with persistent asthma and their
      caregivers comprised the study sample. Audio-recorded provider-caregiver-child
      communication during the baseline medical visit captured discussion of the PFM;
      and child and caregiver baseline interviews after the medical visit collected
      factors associated with PFM use. Child- and caregiver-reported PFM availability
      and use, and observed child use of PFM were collected one-month later in the
      family's home. RESULTS: During the medical visit, provider communication about
      PFM use was infrequent (10% maximum) and child- or caregiver-initiated
      communication was nearly absent (0%-2%). Despite this, children demonstrated good
      use of the PFM one month later. Children were significantly more likely to
      perform at least six PFM steps correctly one month later when there was more
      communication about PFM during the medical visit. Few other factors predicted
      availability and use. CONCLUSIONS: Few providers discussed use of a PFM; observed
      performance was predicted by having talked about it with the child's provider.
      Provider communication should be targeted in future interventions to improve
      asthma management skills.

PMID- 24020681
TI  - Multilevel analysis of the impact of school-level tobacco policies on adolescent
      smoking: the case of Michigan.
AB  - BACKGROUND: In efforts to curb and prevent youth smoking, school tobacco policies
      have become an important and effective strategy. This study explores the degrees
      and types of tobacco-free school policy (TFSP) enforcement that are associated
      with adolescent smoking. METHODS: A multilevel analysis was performed using 983
      students who are nested in 14 schools. The individual-level data are drawn from
      the 2009 Michigan Youth Risk Behavior Survey. The school-level data are drawn
      from the 2008 School Health Profiles survey. RESULTS: Two factors are associated
      with lower adolescent smoking: greater punishment for TFSP violation and more
      tobacco control communication efforts. By contrast, the factors associated with
      higher adolescent smoking are designation of a tobacco-free school zone and
      school-level smoking. CONCLUSIONS: This study theoretically and methodologically
      guides researchers to test TFSP effectiveness in other states. Three strategic
      implications emerge: (1) schools should provide a consistent antismoking message
      in smoke-free environments; (2) schools should integrate TFSP into a
      comprehensive tobacco control initiative, including community-wide tobacco
      control programs and messages; and (3) the way a specific TFSP is promoted and
      communicated could determine how effective it is.

PMID- 24020682
TI  - Peer acceptance in the school class and subjective health complaints: a
      multilevel approach.
AB  - BACKGROUND: Feeling accepted by peers is important for young people's health but
      few studies have examined the overall degree of acceptance in school and its
      health consequences. The purpose of the study was to investigate whether health
      complaints among Swedish students can be attributed to the acceptance climate in
      their school class even when the health effects of their own (individual)
      acceptance score have been taken into account. METHODS: The data used were from
      the Health Behaviour in School-aged Children (HBSC) study for the years 2001 to
      2002, 2005 to 2006, and 2009 to 2010, consisting of 13,902 5th-, 7th-, and 9th
      grade Swedish students nested into 742 school classes. The statistical analyses
      were performed by means of linear regression multilevel analysis. RESULTS: The
      results indicated that the variation in subjective health complaints could be
      ascribed partly to the school-class level (boys: 5.0%; girls: 13.5%). Peer
      acceptance at the individual level demonstrated a clear association with health:
      the lower the acceptance, the higher the complaint scores. For girls, but not for
      boys, the overall degree of peer acceptance in the school class demonstrated a
      contextual effect on health, net of acceptance at the student level. Interaction
      analyses also revealed an increasingly favorable health among poorly accepted
      girls as the acceptance climate in the school class declined. CONCLUSIONS: A
      lower overall degree of peer acceptance in the school class is associated with
      poorer health among girls. However, girls who themselves feel poorly accepted are
      not as negatively affected health-wise by a poor acceptance climate, as are well
      accepted girls.

PMID- 24020683
TI  - Measuring emotion socialization in schools.
AB  - BACKGROUND: Understanding how school personnel can best support students'
      development of communication skills around feelings is critical to long-term
      health outcomes. The measurement of emotion socialization in schools facilitates
      future research in this area; we review existing measures of emotion
      socialization to assess their applicability to school-based health studies.
      METHODS: A content analysis of four emotion socialization measures was conducted.
      Inclusion criteria included: high frequency of use in prior research, established
      documentation of validity and reliability, and sufficient description of
      measurement procedures. RESULTS: Four dimensions emerged as particularly salient
      to a measure's future relevance and applicability to school-based health studies:
      (1) methods of measurement; (2) mode and agent of socialization; (3) type of
      emotion; and (4) structure versus function of socializing behavior. CONCLUSION:
      Future measurement strategies should address (1) the structures of emotion
      socializing processes; (2) diverse socializing agents such as teachers, peers,
      and administrators; (3) the intended functions of such processes; (4) student
      perceptions of and responses to such processes; and (5) the complex interactions
      of these factors across contexts. Strategies attending to these components will
      permit future studies of school-based emotion socializing processes to determine
      how they enhance health and reduce health risks.

PMID- 24020684
TI  - Psychometrics of a brief measure of emotional self-efficacy among adolescents
      from the United States.
AB  - BACKGROUND: Preliminary data were collected to evaluate the psychometric
      properties of an emotional self-efficacy (ESE) measure in a sample of 3836 public
      high school adolescents who completed the Centers for Disease Control and
      Prevention (CDC) Youth Risk Behavior Survey in South Carolina. METHODS: Principal
      axis factor analysis was followed by a 4-way between-groups analysis of variance
      (ANOVA) testing for differences in total score means on selected demographic
      estimates and their interactions. Relationships between total score and selected
      risk behaviors were examined through a series of 1-way ANOVA procedures and
      subsequent Tukey Honest Significant Difference (HSD) tests. RESULTS: Factor
      analysis results suggested that a 1-factor model best explained factor structure
      of the scale items (factor loadings .64 to .71, eigenvalue = 3.24, h(2)  = .46).
      Girls reported a significantly higher mean total ESE rating than boys; White
      students reported a significantly higher mean total ESE rating than Black
      students. Statistically significant lower mean total ESE ratings were also noted
      for those who reported physical fighting, lifetime alcohol use, and sexual
      intercourse. CONCLUSION: This 7-item scale is a reliable measure and could aid
      school health researchers and mental health practitioners in psychosocial
      screening and as an outcome of social and emotional learning as a brief measure
      of adolescent ESE.

PMID- 24020685
TI  - Behavioral health emergencies managed by school nurses working with adolescents.
AB  - BACKGROUND: As members of interdisciplinary teams, school nurses provide
      behavioral health services. Studies indicate that school nurses may lack
      sufficient continuing education in adolescent behavioral health and in the
      management of behavioral health emergencies, specifically. We conducted this
      study to describe the adolescent behavioral health emergencies managed by school
      nurses. METHODS: We used data from a New Mexico public school nurse workforce
      survey to describe the involvement of school nurses in managing adolescent
      behavioral health emergencies. We included all respondents who self-identified as
      working in a secondary school (N = 186). We conducted descriptive analyses.
      RESULTS: Two thirds of survey respondents had provided emergency management in
      the prior school year for child abuse or neglect, depression, and violence at
      school. Over 40% had provided emergency management for a suicidal student in the
      prior school year. Although almost 80% of respondents identified "violence at
      school" as a very important continuing education topic, 40% reported having
      received continuing education on this topic in the prior 5 years. CONCLUSIONS: In
      New Mexico, public school nurses provide substantial amounts of emergency
      management for adolescent behavioral health problems. Continuing education
      received by school nurses on behavioral health emergencies may not be
      commensurate with their clinical responsibilities.

PMID- 24020686
TI  - Development of a pre-service teachers' self-efficacy instrument regarding teacher
      health education standards.
AB  - BACKGROUND: Whereas many education programs expect students to use national
      standards in various content areas, few studies have been conducted that examine
      pre-service teachers' confidence in demonstrating their use of the professional
      teacher standards. PURPOSE: The purpose of this project was 2-fold: (1) To
      develop the Pre-service Health Education National Standards Self-efficacy
      (PHENSS) Scale; and (2) To establish the instrument's ability to draw inferences
      from PHENSS Scale scores. METHODS: The final instrument consisted of 29 items and
      4 demographic items. Validation was established using qualitative and
      quantitative procedures. After the instrument had been validated, pre-service
      elementary education and pre-service secondary health education teachers were
      recruited to complete the instrument at 2 different times. RESULTS: Items were
      grouped to form 7 subscales (a subscale for each standard) and were analyzed to
      determine test-retest reliability and internal consistency. All scales were found
      to be statistically significant (p <= .05). Cronbach's alpha for the 7 subscales
      ranged from .73 to .96, and alpha = .94 for the entire instrument. CONCLUSION:
      The instrument, which assessed self-efficacy toward implementing Professional
      Teacher Standards in Health Education, was found to be both valid and reliable.

PMID- 24020687
TI  - The nutritional role of flavored and white milk in the diets of children.
AB  - BACKGROUND: Some schools are removing flavored milk from lunchrooms based on the
      perception that consumption has a negative impact on the overall dietary quality.
      The goal of this study was to assess the contribution of flavored and white milk
      in the diets of children. METHODS: Intake data from children 2 to 18 years (N =
      7332) participating in the National Health and Nutrition Examination Survey
      (NHANES) 2003-2006 were obtained from in-person 24-hour dietary recalls. Mean +/-
      standard error of energy and nutrients were determined. RESULTS: Flavored and
      white milk contributed, respectively, 2-6% of total energy consumed, 3-12% of
      saturated fats, 1-3% of sodium, and 4-0% of added sugars. The percent
      contribution of white milk to intakes of vitamin A (21%), vitamin D (54%),
      calcium (29%), potassium (17%), magnesium (12%), and phosphorus (19%) exceeded
      10% of total intake. Consumption of flavored milk contributed a smaller
      percentage to total intake. For total dairy consumed the percent contribution to
      intake of vitamins A and D, calcium, potassium, magnesium, and phosphorus ranged
      from 19% to 68%. CONCLUSIONS: Milk has an important nutritional role in the diets
      of children. More research is needed to understand the barriers to consuming milk
      and potential unintended nutrition consequences of removing flavored milk from
      the lunchrooms.

PMID- 24020688
TI  - Trends in professional development for and collaboration by health education
      teachers--41 states, 2000-2010.
AB  - BACKGROUND: Professional development (PD) and collaboration help ensure the
      quality of school health education. The purpose of this study was to examine
      trends in the percentage of lead health education teachers (LHETs) receiving PD
      on health topics and collaborating with other school staff on health education
      activities. METHODS: This study analyzed representative data from 41 states
      participating in School Health Profiles surveys between 2000 and 2010. Logistic
      regression examined linear trends in the percentage of LHETs who received PD on
      12 topics and who collaborated on health education activities. RESULTS:
      Significant increases in the percentage of LHETs receiving PD on nutrition and
      physical activity and significant decreases in the percentage of LHETs receiving
      PD on alcohol- and other drug-use prevention and human immunodeficiency virus
      prevention were seen. Significant increases in the percentage of LHETs who
      collaborated with physical education staff and nutrition services staff were seen
      in 29 and 39 states, respectively. CONCLUSIONS: Although 10-year increases in PD
      and collaboration in the areas of nutrition and physical activity are
      encouraging, PD and collaboration in other topic areas still need improvement.
      These results will help states target more resources toward PD and collaboration
      in areas where they have been decreasing.

PMID- 24020689
TI  - How school healthy is your state? A state-by-state comparison of school health
      practices related to a healthy school environment and health education.
AB  - BACKGROUND: School Health Profiles (Profiles) results help states understand how
      they compare to each other on specific school health policies and practices. The
      purpose of this study was to develop composite measures of critical Profiles
      results and use them to rate each state on their overall performance. METHODS:
      Using data from state Profiles surveys conducted in 2010, the authors examined 12
      key practices: 6 related to a healthy school environment and 6 related to health
      education. States were divided into quartiles based on the percentage of schools
      in the state that engaged in the practice, and then rank-ordered based on the sum
      of their quartile scores. RESULTS: Whereas some states have low ranks or high
      ranks in both sets of practices, others have a relatively low rank in one set but
      a high rank in the other. States with the lowest overall sums tend to be in the
      west and midwest, whereas states with the highest sums tend to be in the east.
      CONCLUSIONS: This study identifies states whose school health policies and
      practices should be emulated and other states whose policies and practices are in
      urgent need of improvement.

PMID- 24020690
TI  - Association of UV index and sunscreen use among White high school students in the
      United States.
AB  - BACKGROUND: When used appropriately, sunscreen decreases the amount of
      ultraviolet (UV) radiation exposure to the skin and is recommended to prevent
      skin cancer. This study examined the association between annual average UV index
      and sunscreen use among White, non-Hispanic youth. METHODS: The 2007 and 2009
      national Youth Risk Behavior Survey (YRBS) data were analyzed. The YRBS is a
      school-based, cross-sectional study that uses a 3-stage cluster sample design to
      obtain a nationally representative sample of public and private high school
      students in the United States. Overall response rates were 68% and 72% (N =
      14,041 and 16,410, respectively). Logistic regression analyzes, controlling for
      grade, examined whether annual average (mean) UV index where students attend
      school, a proxy measure of potential sunlight exposure, was associated with
      sunscreen use. RESULTS: Among White male students, as the mean UV index
      increased, the adjusted odds of never wearing sunscreen increased (adjusted odds
      ratio, AOR = 1.15 [95% CI = 1.04, 1.27], p < .01) and the adjusted odds of most
      of the time or always wearing sunscreen decreased (AOR = 0.85 [0.78, 0.94], p <
      .01). There was no association between sunscreen use and mean UV index among
      White female students. CONCLUSION: These findings suggest a need for renewed
      public health efforts among school, clinical, and public health professionals to
      promote sunscreen use as part of a comprehensive approach to prevent skin cancer.
      School and community approaches that passively protect young people from the sun
      should be considered as a complement to efforts to increase sunscreen use.

PMID- 24020691
TI  - The potential role of fruit and vegetables in aspects of psychological well
      being: a review of the literature and future directions.
AB  - The objective of the present paper was to review the literature investigating the
      potential relationship between fruit and vegetables (FV) and psychological well
      being. The rising prevalence of mental ill health is causing considerable
      societal burden. Inexpensive and effective strategies are therefore required to
      improve the psychological well-being of the population, and to reduce the
      negative impact of mental health problems. A growing body of literature suggests
      that dietary intake may have the potential to influence psychological well-being.
      For example, studies have suggested that particular dietary constituents,
      including vitamins and minerals, might be beneficial to psychological health.
      However, in order to better reflect normal dietary intake, health-based research
      has increasingly begun to focus on whole foods and dietary patterns, rather than
      individual nutrients. One food group that has received increasing attention with
      regard to psychological health is FV. This is probably a result of the strong
      evidence base, which exists in relation to their protective association with a
      number of chronic diseases, as well as the fact that they are a rich source of
      some of the nutrients which have been linked to psychological health. While some
      promising findings exist with regards to FV intake and psychological well-being,
      overall, results are inconsistent. Possible reasons for this, such as
      methodological issues related to study design and the measurement of
      psychological well-being and FV intake, are discussed within this review. Based
      on the predominantly observational nature of existing literature, the present
      paper concludes that future well-designed randomised controlled trials are
      required to investigate the relationship further.

PMID- 24020692
TI  - Assessing core outcomes in graduates: psychometric evaluation of the Paediatric
      Intensive Care Unit-Nursing Knowledge and Skills Test.
AB  - AIM: To develop and psychometrically test the Paediatric Intensive Care Unit
      Nursing Knowledge and Skills Test - a multiple-choice test for measuring the key
      nursing knowledge and skills required for safe, competent practice. BACKGROUND:
      Intensive care graduate nurse residency or orientation programmes are key
      strategies in the development of safe and competent practitioners. Essential to
      these programmes is an evaluation of knowledge and skills. Multiple-choice
      examinations provide a valuable way of evaluating broad knowledge and skills;
      however, there has been limited work in this area to date. DESIGN: Psychometric
      evaluation. METHODS: The instrument was administered to 79 nurses from four
      paediatric intensive care units in Australia and New Zealand over 18 months
      between 2008-2010. Internal consistency using Kuder-Richardson 20, item analysis
      and construct validity using the 'known groups' technique were explored. RESULTS:
      Kuder-Richardson 20 reliability estimate for the 109-item test was 0.85.
      Instrument scores were significantly higher amongst nurses with postgraduate
      education and more years of paediatric intensive care experience. Item difficulty
      indices ranged from 0.08 to 1, with a mean item difficulty of 0.66. Item
      discrimination ranged from 0.2-0.8. CONCLUSION: Testing of the instrument
      demonstrated encouraging psychometric properties. With additional refinement,
      this tool could provide educators and managers with an instrument to assist in
      the assessment of knowledge and skill acquisition. The instrument requires
      further testing in different samples of paediatric intensive care nurses to
      enable validation in other settings and cross-cultural comparisons.

PMID- 24020694
TI  - Superpressing of a room temperature ionic liquid, 1-ethyl-3-methylimidazolium
      tetrafluoroborate.
AB  - We have investigated the phase behavior of 1-ethyl-3-methylimidazolium
      tetrafluoroborate ([emim][BF4]) at 298 K under high pressure conditions. We found
      that [emim][BF4] can be superpressed without crystallization up to ~7 GPa. We
      propose that [emim][BF4] behaves as a superpressurized glass above 2.8 GPa. In
      view of the results, the environment around the alkyl-chain (C6 and C7-C8) of
      [emim][BF4] is largely perturbed rather than that around the imidazolium-ring in
      the superpressed state. We also discussed the results in view of the
      conformational isomerism of [emim](+) cation. Remarkably, as an alternative to
      pressure-induced crystallization, we have found that such a metastable liquid
      shows crystal polymorphism around 2.0 and 1.0 GPa upon decompression. The
      behavior is in contrast with the earlier results of 1-butyl-3-methylimidazolium
      tetrafluoroborate ([bmim][BF4]). 

PMID- 24020695
TI  - Pluripotent and somatic stem cells: from basic science to utilization in disease
      modeling and therapeutic application. Meeting report on the 7th International
      Meeting of the Stem Cell Network North Rhine Westphalia.

PMID- 24020696
TI  - Tracking induced pluripotent stem cells-derived neural stem cells in the central
      nervous system of rats and monkeys.
AB  - Despite of the immense breakthroughs of induced pluripotent stem cells (iPSCs),
      clinical application of iPSCs and their derivates remains hampered by a lack of
      definitive in vivo studies. Here, we attempted to track iPSCs-derived neural stem
      cells (NSCs) in the rodent and primate central nervous system (CNS) and explore
      their therapeutic viability for stem cell replacement in traumatic brain injury
      (TBI) rats and monkeys with spinal cord injury (SCI). Superparamagnetic iron
      oxide (SPIO) particles were used to label iPSCs-derived NSCs in vitro. Labeled
      NSCs were implanted into TBI rats and SCI monkeys 1 week after injury, and then
      imaged using gradient reflection echo (GRE) sequence by 3.0T magnetic resonance
      imaging (MRI) scanner. MRI analysis was performed at 1, 7, 14, 21, and 30 days,
      respectively, following cell transplantation. Pronounced hypointense signals were
      initially detected at the cell injection sites in rats and monkeys and were later
      found to extend progressively to the lesion regions, demonstrating that iPSCs
      derived NSCs could migrate to the lesion area from the primary sites. The
      therapeutic efficacy of iPSCs-derived NSCs was examined concomitantly through
      functional recovery tests of the animals. In this study, we tracked iPSCs-derived
      NSCs migration in the CNS of TBI rats and SCI monkeys in vivo for the first time.
      Functional recovery tests showed obvious motor function improvement in
      transplanted animals. These data provide the necessary foundation for future
      clinical application of iPSCs for CNS injury.

PMID- 24020698
TI  - A tribute to Keith Campbell: the birth of the first clone of an adult vertebrate,
      "Dolly" the sheep.

PMID- 24020697
TI  - Slow turning lateral vessel bioreactor improves embryoid body formation and
      cardiogenic differentiation of mouse embryonic stem cells.
AB  - Embryonic stem cells (ESCs) have the ability to form aggregates, which are called
      embryoid bodies (EBs). EBs mimic early embryonic development and are commonly
      produced for cardiomyogenesis. Here, we describe a method of EB formation in
      hydrodynamic conditions using a slow-turning lateral vessel (STLV) bioreactor and
      the subsequent differentiation of EBs into cardiomyocytes. EBs formed in the STLV
      were compared with conventional techniques, such as hanging drop (HD) or static
      suspension cell culture (SSC), for homogeneity of EB size, shape, proliferation,
      apoptosis, and in vitro cardiac differentiation. After 3 days of culture, a four
      fold improvement in the yield of EB formation/mL, a six-fold enhancement in total
      yield of EB/mL, and a nearly 10-fold reduction of cells that failed to
      incorporate into EBs were achieved in STLV versus SSC. During cardiac
      differentiation, a 1.5- to 4.2-fold increase in the area of cardiac troponin T
      (cTnT) per single EB in STLV versus SSC and HD was achieved. These results
      demonstrate that the STLV method improves the quality and quantity of ES cells to
      form EBs and enhances the efficiency of cardiac differentiation. We have
      demonstrated that the mechanical method of cell differentiation creates different
      microenvironments for the cells and thus influences their lineage commitments,
      even when genetic origin and the culture medium are the same. Ascorbic acid (ASC)
      improved further cardiac commitment in differentiation assays. Hence, this
      culture system is suitable for the production of large numbers of cells for
      clinical cell replacement therapies and industrial drug testing applications.

PMID- 24020700
TI  - Keith's MAGIC: Cloning and the Cell Cycle.
AB  - Abstract Professor Keith Campbell's critical contribution to the discovery that a
      somatic cell from an adult animal can be fully reprogrammed by oocyte factors to
      form a cloned individual following nuclear transfer (NT)(Wilmut et al., 1997 )
      overturned a dogma concerning the reversibility of cell fate that many scientists
      had considered to be biologically impossible. This seminal experiment proved the
      totipotency of adult somatic nuclei and finally confirmed that adult cells could
      differentiate without irreversible changes to the genetic material. 

PMID- 24020701
TI  - Structural investigation of the substituted pyrochlore AgSbO3 through total
      scattering techniques.
AB  - Polycrystalline samples of the pyrochlore series Ag(1-x)M(n)(x)SbO(3+x[(n-1)/2])
      (M = Na, K, and Tl) have been structurally analyzed through total scattering
      techniques. The upper limits of x obtained were 0.05 for Na, 0.16 for K, and 0.17
      for Tl. The Ag(+) cation occupies a site with inversion symmetry on a 3-fold
      axis. When the smaller Na(+) cation substitutes for Ag(+), it is displaced by
      about 0.6 A perpendicular to the 3-fold axis to achieve some shorter Na-O bond
      distances. When the larger Tl(+) cation substitutes for Ag(+), it is displaced by
      about 1.14 A along the 3-fold axis and achieves an environment typical of a lone
      pair cation. Some of the Tl(3+) from the precursor remains unreduced, leading to
      a formula of Ag(0.772(1))Tl(+)(0.13(2))Tl(3+)(0.036(1))SbO(3.036(1)). The
      position of the K(+) dopant was effectively modeled assuming that K(+) occupied
      the same site as Ag(+). The expansion of the lattice caused by substitution of
      the larger K(+) and Tl(+) cations results in longer Ag-O bond lengths, which
      would reduce the overlap of the Ag 4d and O 2p orbitals that compose the valence
      band maximum. Substitution of the smaller Na(+) results in a decrease in the Ag-O
      bond distance, thus increasing the overlap of the Ag 4d and O 2p orbitals. This
      will have a direct influence on the band composition and observed properties of
      this material of interest.

PMID- 24020699
TI  - Silencing histone deacetylase-specific isoforms enhances expression of
      pluripotency genes in bovine fibroblasts.
AB  - Histone deacetylases (HDACs) catalyze deacetylation of histones that results in
      altered transcriptional activity. Inhibitors of HDACs have been shown to induce
      transcriptional changes that contribute positively to reprogramming somatic cells
      either by nuclear transfer or inducing a pluripotent state. However, the exact
      molecular mechanisms whereby HDAC inhibitors function and the specificity of the
      HDAC isoforms in cell reprogramming are not yet fully understood. Herein, we
      report the ability of individual isoform-specific HDACs to modulate endogenous
      expression of pluripotency-associated genes in bovine somatic cells. This in
      vitro study showed that a transient selective depletion of HDACs resulted in
      elevated mRNA levels of Oct-4, Sox2, and Nanog. In particular, we found that
      inhibition of specific HDAC isoforms using small interfering (si) RNA
      significantly increased expression of Nanog, a key factor required for
      totipotency induced by somatic cell nuclear transfer and for maintaining
      pluripotency in embryonic and induced pluripotent stem cells. Our study suggests
      that this gene might be the most susceptible to HDAC activity inhibition.
      Moreover, a regulatory role of the class III HDAC, SIRT3, on an Oct4-Sox2-Nanog
      transcriptional network was revealed. We observed the upregulation of
      pluripotency-related genes by depletion of SIRT3. SIRT3 is localized to
      mitochondria and is associated with energy metabolism processes, suggesting
      metabolic changes may be linked to reprogramming in bovine fibroblasts. In
      conclusion, we show that targeting selective HDACs can potentially be useful to
      enhance reprogramming and that sirtuins may play a pivotal role in somatic cell
      reprogramming by upregulating an Oct4-Sox2-Nanog transcriptional network.
      Dedifferentiating donor somatic cells by upregulating developmentally important
      genes through specific knockdown of epigenetic targets, in particular HDACs, may
      provide a path to improving livestock cloning and the in vitro production of
      pluripotent cells.

PMID- 24020703
TI  - Inflammatory pseudotumour of urinary bladder - a rare cause of massive
      macroscopic haematuria.
AB  - PURPOSE: Authors analyzed their experience with urinary bladder tumours. This
      article discusses clinical and histopathological diagnostics and treatment
      procedures, and follow up of patients with rare benign urinary bladder tumours.
      METHODS: 406 patients with bladder tumours were treated in our department between
      January 2000 and December 2008. 322 patients had superficial tumours and 84 had
      primary invasive tumours. All patients who underwent transurethral resections of
      these tumours were operated under general or spinal anaesthesia. The resected
      specimens were histologically examined in the department of Pathology. RESULTS:
      399 of the 406 patients had urothelial bladder cancer, 7 patients had a
      histologically uncommon type of bladder tumour, one female was diagnosed with
      sarcomatoid bladder cancer, one patient had a histologically confirmed
      feochromocytoma of the urinary bladder. Two males had epidermoid carcinoma. One
      female had a histologically described uncommon benign pseudoneoplastic lesion,
      chararacteristic for endosalpingiosis. Another two patients were diagnosed with
      inflammatory myofibroblastic tumour of the urinary bladder. Both patients
      presented with gross macroscopic haematuria. Authors performed complete
      transurethral tumour resections, which required several sessions and the
      deliberation of a blocked ureter through nephrostomy in one case. CONCLUSION:
      More than 98 % of all treated patients had urothelial bladder cancer in different
      stages and grades. Two patients had rare benign inflammatory proliferation of the
      bladder wall which formed large tumorous bleeding masses obstructing the ureter
      in one case. These types of bladder tumour could be treated conservatively with
      meticulous long term follow up similarly to patients with bladder cancer (Tab. 1,
      Fig. 4, Ref. 15). .

PMID- 24020702
TI  - The prevalence and correlates of sitting in European adults - a comparison of 32
      Eurobarometer-participating countries.
AB  - BACKGROUND: Prolonged sitting is an emerging health risk. However, multi-country
      comparative sitting data are sparse. This paper reports the prevalence and
      correlates of sitting time in 32 European countries. METHODS: Data from the
      Eurobarometer 64.3 study were used, which included nationally representative
      samples (n = 304-1,102) from 32 European countries. Face-to-face interviews were
      conducted during November and December 2005. Usual weekday sitting time was
      assessed using the International Physical Activity Questionnaire (short-version).
      Sitting time was compared by country, age, gender, years of education, general
      health status, usual activity and physical activity. Multivariable-adjusted
      analyses assessed the odds of belonging to the highest sitting quartile. RESULTS:
      Data were available for 27,637 adults aged 15-98 years. Overall, mean reported
      weekday sitting time was 309 min/day (SD 184 min/day). There was a broad
      geographical pattern and some of the lowest amounts of daily sitting were
      reported in southern (Malta and Portugal means 194-236 min/day) and eastern
      (Romania and Hungary means 191-276 min/day) European countries; and some of the
      highest amounts of daily sitting were reported in northern European countries
      (Germany, Benelux and Scandinavian countries; means 407-335 min/day).
      Multivariable-adjusted analyses showed adults with low physical activity levels
      (OR = 5.10, CI95 = 4.60-5.66), those with high sitting in their main daily
      activity (OR = 2.99, CI95 = 2.74-3.25), those with a bad/very bad general health
      state (OR = 1.87, CI95 = 1.63-2.15) and higher education levels (OR = 1.48, CI95
      = 1.38-1.59) were more likely to be in the highest quartile of daily sitting
      time. Adults within Greece (OR = 2.91, CI95 = 2.51-3.36) and Netherlands (OR =
      2.56, CI95 = 2.22-2.94) were most likely to be in the highest quartile. High
      sit/low-active participants comprised 10.1% of the sample. Adults self-reporting
      bad/very bad general health state (OR = 4.74, CI95 = 3.97-5.65), those within
      high sitting in their main daily activities (OR = 2.87, CI95 = 2.52-3.26) and
      adults aged >=65 years (OR = 1.53, CI95 = 1.19-1.96) and were more likely to be
      in the high-sit/low-active group. CONCLUSIONS: Weekday sitting time and its
      demographic correlates varied considerably across European countries, with adults
      in north-western European countries sitting the most. Sitting is prevalent across
      Europe and merits attention by preventive interventions.

PMID- 24020704
TI  - Analysis of expression of TNF-alpha and TGF-beta3 in intrinsic ureteropelvic
      junction obstruction.
AB  - OBJECTIVES: Ureteropelvic junction (UPJ) obstruction is of critical importance to
      understand the histopathology of UPJ obstruction in terms of therapy planning and
      follow-up. For this purpose, our study was conducted with TNF-alpha and TGF-beta
      markers to investigate possible underlying problems in intrinsic UPJ obstruction.
      METHODS: Of the patients who had undergone surgery in our clinic, 36 UPJ segments
      of patients who had undergone dismembered pyeloplasty surgery due to UPJ
      obstruction and 14 UPJ segments of the patients who had undergone nephrectomy
      were collected to form 2 groups. All histological sections were examined by
      applying immunohistochemical transforming growth factor beta 3 (TGF-beta3) and
      tumour necrosis factor alpha (TNF-alpha) monoclonal antibody dyes. RESULTS: The
      mean staining values for TNF-alpha in mucosal tissue and mucosa were 0.53+/-0.84
      and 0.58+/-0.84, respectively in the obstruction group, whereas the values
      observed in the control group were 0.86+/-0.36 and 0.93+/-0.47, respectively.
      While the mean staining values in the obstruction group in mucosal tissue and
      mucosa for TGF-beta3 were 1.75+/-0.73 and 2.17+/-0.77, respectively, the values
      established in the control group were 1.14+/-0.66 and 1.43+/-0.93, respectively.
      The difference between the obstruction and control groups were statistically
      significant for both values (p<0.05). CONCLUSION: Only a limited number of
      studies have been carried out on this particular issue. Data from the present
      study indicate that TGF-beta3 and TNF-alpha may play a role in the
      histopathogenesis of UPJ obstruction (Tab. 1, Fig. 1, Ref. 18).

PMID- 24020705
TI  - Nitrites and nitrates in exhaled breath condensate in cystic fibrosis: relation
      to clinical parameters.
AB  - OBJECTIVES: To evaluate correlation of exhaled breath condensate (EBC) nitrite
      and nitrate concentrations with disease severity in cystic fibrosis (CF)
      patients. BACKGROUND: Nitrites and nitrates are products of oxidative metabolism
      of nitric oxide. Impaired metabolism of nitric oxide plays a role in pathogenesis
      of CF. METHODS: EBC was collected from 46 stable CF patients and from 21 healthy
      controls. EBC concentrations of nitrites and nitrates were correlated with
      parameters of lung disease and nutritional status and with systemic inflammatory
      markers. RESULTS: EBC nitrates concentrations in CF patients were lower than in
      healthy subjects (5.8 vs 14.3 MUmol/l, p<0.001). They correlated positively with
      FEV1 (p=0.025) and serum albumin values (p=0.016) and negatively with chest
      radiograph Northern score (p=0.015) and serum C-reactive protein values
      (p=0.005). EBC nitrites concentrations in CF patients did not differ from those
      in healthy subjects and were not correlated to any studied parameter.
      CONCLUSIONS: EBC nitrates concentrations correlate with disease severity in CF
      patients and are lower than in healthy subjects (Tab. 4, Fig. 1, Ref. 48).

PMID- 24020706
TI  - Preeclamptic cord blood hemolysis and the effect of Monascus purpureus and
      Saccharomyces cerevisiae in modulating preeclamptic stress.
AB  - BACKGROUND: Preeclampsia is associated with impaired antioxidant defense that
      results in materno- fetal complications. In addition to antioxidant deficiency,
      hemolytic disorder has also been observed in preeclamptic mother. METHODS: This
      study aims in analyzing the fetal complications using cord blood RBC (red blood
      cell); further the antihemolytic and antioxidant efficiency of two common
      probiotic yeasts Monascus purpureus and Saccharomyces cerevisiae in preeclamptic
      and normotensive RBCs were assessed. RESULTS: There was a significant decrease in
      the antioxidant status (p<0.05) with increased oxidative stress, nitrative stress
      (p<0.05) and hemolysis (p<0.001) in preeclamptic RBC comparatively. M. purpureus
      demonstrated a highly significant reactive oxygen radical scavenging activity
      (p<0.001) whereas S. cerevisiae exhibited a highly significant nitric oxide
      radical scavenging activity (p<0.001). It was noted that oxidative stress
      hemolysis was decreased with increased antioxidant level in cord blood RBC from
      both samples after incubation with both yeasts in a similar manner. The
      antihemolytic property of M. purpureus and S. cerevisiae suggests that S.
      cerevisiae functions efficiently with increasing stress. CONCLUSION: This study
      demonstrates for the first time that despite their differential scavenging
      activities, a diet rich in M. purpureus and S. cerevisiae could equally serve as
      a good natural supplement to alleviate the stress status in the preeclamptic
      fetus (Tab. 4, Fig. 1, Ref. 39).

PMID- 24020707
TI  - Comparison of propofol-dexmedetomidine, tiopental-dexmedetomidine and etomidate
      dexmedetomidine combinations' effects on the tracheal intubation conditions
      without using muscle relaxants.
AB  - BACKGROUND: In our study, we aimed to compare the endotracheal intubation
      conditions without muscle relaxants during induction with the combinations of
      dexmedotimidine-propofol, dexmedotimidine-thiopenthal and dexmedetomidine
      etomidate. METHOD: Seventy-six patients, in ASA risk group I-II, between ages 20
      60 years, with Mallampati Class 1 were included in the study. All patients were
      premedicated with midazolam. The patients were randomly divided into three groups
      as Group P (n=30, dexmedetomidine-propofol), Group T (n=30, dexmedetomidine
      thiopenthal), Group E (n=16, dexmedetomidine-etomidate). All patients received
      dexmedetomidine 1 MUg.kg-1 in 10 min. Then, the patients were administered 2.5
      mg.kg-1 propofol for Group P, 5 mg.kg-1 thiopental for Group T and 0.3 mg.kg-1
      etomidate for Group E during induction. Hemodynamic data of the patients were
      recorded before induction, after dexmedetomidine administration, immediately
      after intubation and 3, 5 and 10 minutes after intubation. RESULTS: There was no
      difference between the groups according to hemodynamic data. Sixteen patients in
      Group P and 10 patients in Group T had acceptable intubation conditions. Muscle
      relaxant was needed in 14, 20 and 16 patients in Groups P, T and E, respectively
      (p<0.05). CONCLUSION: In conclusion, we determined that best intubation
      conditions without muscle relaxants were achieved with propofol-dexmedetomidine
      combination. None of the patients receiving etomidate -dexmedetomidine
      combination could be intubated without muscle relaxants (Tab. 6, Ref. 29).

PMID- 24020708
TI  - Blunt trauma - related isolated pancreatic injury.
AB  - BACKGROUND: Pancreatic injuries arising from blunt trauma are rarely seen.
      Diagnosis and treatment are difficult because of retroperitoneal localization of
      the organ. We present four pancreatic cases with isolated pancreatic injury due
      to blunt abdominal trauma. METHODS: This retrospective study included four
      pancreatic patients who were operated on due to isolated injury caused by blunt
      abdominal trauma at our department between January 2004 and October 2010.
      RESULTS: The patients consisted of three males and one female. One of them was in
      stage IV and the rest were in stage III. All underwent pancreaticojejunostomy,
      distal pancreatectomy, distal pancreatectomy + splenectomy and drainage,
      respectively. Fistula developed in two of them, and abscess developed in one,
      while the other one died. CONCLUSION: Diagnosis may be delayed since the clinical
      condition is initially stable. Tomography remains one of the most important
      diagnostic tools. Common risk factors for morbidity and mortality are the
      presence of ductal injury and delayed laparotomy (Tab. 1, Fig. 4, Ref. 22).

PMID- 24020709
TI  - Beta-Thalassemia major and pregnancy.
AB  - OBJECTIVE: It was studied the clinical management and the medical outcomes of 6
      pregnancies in 5 women affected by Beta Thalassemia major, based on last
      guidelines and pharmacological treatments. BACKGROUND: Paediatric Department and
      Department of Obstetrics and Gynaecology of the University of Catania. METHODS:
      These patients were taken among a group of 116 women affected by beta-thalassemia
      major divided into three subgroups, according to the characteristics of their
      menstrual cycle: 1) women with primitive amenorrhoea, 2) women with secondary
      amenorrhoea and 3) women with normal menstruation. Only one woman, affected by
      primitive amenorrhoea, needed the induction of ovulation. An accurate and
      detailed pre-pregnancy assessment was effected before each conception. This was
      constituted by a series of essays, including checks for diabetes and
      hypothyroidism, for B and C hepatitis and for blood group antibodies. Moreover
      were evaluated: cardiac function, rubella immunity and transaminases. Other
      pregnancy monitoring, and cares during labour and delivery were effected
      according to usual obstetrics practice. RESULTS: All the women were in labour
      when they were 38 week pregnant, and the outcome were six healthy babies born at
      term. There were no complications related to the pregnancy and to the immediate
      outcome after delivery. CONCLUSIONS: The improvements of current treatments,
      especially in the management of iron deposits, the prolongation of survival rate,
      will result in a continuous increase of pregnancies in thalassemic women.
      Pregnancy is now a real possibility for women affected by such disease. Although
      numerous complications can occur, vigilant monitoring by both experienced
      obstetricians and hematologists can lead to successful pregnancy outcomes (Tab.
      1, Fig. 1, Ref. 16).

PMID- 24020710
TI  - Left ventricular systolic and diastolic function in children with overweight and
      obesity.
AB  - OBJECTIVES: Several studies have found an association between obesity and heart
      failure. The purpose of our study was to identify the influence of the severity
      of obesity in children on structural and functional changes of the left ventricle
      and parameters of the systolic and diastolic function. METHODS: This was a
      prospective controlled study carried out between February 1 and October 31, 2010,
      involving 21 children with overweight and obesity and 23 healthy controls.
      Following parameters were evaluated: nutritional status, intermittent and
      continuous ambulatory blood pressure monitoring, echocardiographic examination
      including aortal root diameter, left atrial diameter, interventricular septum
      thickness, left ventricular end-diastolic diameter, left ventricular end-systolic
      diameter, left ventricular posterior wall thickness, left ventricle mass,
      relative wall thickness, left ventricular mass/height index and ejection
      fraction. RESULTS: In overweight and obese children, systolic blood pressure,
      diastolic blood pressure, average day-time SBP were higher than in controls.
      Also, left ventricular size was increased and diastolic dysfunction with
      preserved systolic function was present in overweight children. CONCLUSIONS: In
      our study we have found that in obese and overweight children signs of early
      myocardial damage, both structural and functional, are detectable mainly as the
      alteration of the left ventricular diastolic function, despite preserved global
      systolic function. These changes seem to be intensified by the severity of
      obesity (Tab. 3, Ref. 39).

PMID- 24020711
TI  - Risk factors for peritonitis related to peritoneal dialysis.
AB  - BACKGROUND: The aim of this study was to evaluate risk factors for peritonitis
      associated with peritoneal dialysis in our centre. METHODS: Forty patients on
      chronic peritoneal dialysis between 2006-2010 were enrolled in this study.
      Nutritional, sociodemographical, psychological, dialysis related (peritoneal
      modality, characteristics and adequacy) possible risk factors associated with the
      development of peritonitis were recorded. Data of patients with and without
      peritonitis were compared using the Student's t-test and chi-square test.
      RESULTS: There were 31 episodes of peritonitis among 21 patients, while other 19
      patients had not experienced peritonitis resulting in a rate of 1 episode / 44
      patient months. Staphylococcus aureus was the most frequent microorganism
      isolated (31 %). Hypoalbuminemia, technical problems, poor personal and
      environmental hygiene, low educational status, current or former smoking history
      and less urine output were observed significantly more in patients who had
      peritonitis. CONCLUSIONS: Our results confirm that educational, psychological,
      nutritional, smoking and hygiene status and amount of urine output are closely
      associated with peritonitis among peritoneal dialysis patients. Measures to
      improve these factors may help prevent and control peritoneal dialysis related
      peritonitis (Tab. 4, Ref. 14).

PMID- 24020712
TI  - Is the Arthritis Impact Measurement Scales 2 a good tool to assess quality of
      life in Slovak patients with rheumatoid arthritis?
AB  - OBJECTIVES: The aim of this study is to evaluate the measurement properties of
      the Arthritis Impact Measurement Scales 2 (AIMS2) in Slovak patients with
      rheumatoid arthritis (RA). BACKGROUND: RA impacts all aspects of life quality
      (QoL). Many instruments for QoL in RA patients frequently assess only biological
      aspects. The AIMS2 instrument covers physical, emotional and social QoL and it is
      widely and successfully used as an indicator of the outcomes of care for
      arthritis patients, but not in Slovak RA patients. METHODS: After translation 178
      patients with RA were asked to complete the AIMS2, Visual Analogue Scale for pain
      - VAS, Health Assessment Questionnaire Disability Index - HAQ-DI, Beck Anxiety
      Inventory - BAI and Zung Self-Rating Depression Scale - SDS to analyse the
      validity of the Slovak-AIMS2. Pearson correlations, one-way analysis of variance
      (ANOVA), t-test, and principal component analysis were used to test validity of
      AIMS2. The reliability was assessed by internal consistency, as estimated by
      Cronbach's alpha coefficients, and using the test-retest procedure. RESULTS: The
      Cronbach's alpha coefficients for AIMS2 scales ranged from 0.78 to 0.94, the test
      retest reliability was significant (p<0.05), ranging from 0.61 to 0.99. The
      correlations between most of the Slovak-AIMS2 scales and HAQ-DI, VAS, BAI and SDS
      were statistically significant (p<0.05). The principal component analysis
      identified three factor models explaining 66.82 % of the variance. CONCLUSIONS:
      The results showed that Slovak-AIMS2 is culturally appropriate, valid and
      reliable for measuring the health status in adult RA patients (Tab. 6, Ref. 20).

PMID- 24020713
TI  - Effects of probiotics and prebiotics in ulcerative colitis.
AB  - OBJECTIVES: Inflammatory bowel diseases (IBD) are caused by the failure of
      immunoregulatory mechanisms due to external environmental factors in genetically
      predisposed individuals. Probiotics and prebiotics could be used in prevention
      and therapy of many disorders of gastrointestinal tract including ulcerative
      colitis. Probiotics are living microorganisms with good tolerability and minimal
      risk, which confer a health benefit for the host when administered in adequate
      amounts. Their effect is closely related to maintaining the natural function of
      the intestinal flora. In this respect, they are indispensable prebiotics to
      protect or reduce the incidence of inflammatory lesions in diseases of the
      digestive tract. CONCLUSION: Ingestion of probiotics and prebiotics may provide
      some clues in developing a new class of therapeutic agents for the treatment/
      prevention of IBD and colitis-associated cancer (CAC) in the future (Tab. 2, Ref.
      26).

PMID- 24020714
TI  - Relapse of hyperthyroidism after hemithyroidectomy in concurrent medullary
      thyroid cancer and Graves' disease.
AB  - We present a rare case of concurrent medullary thyroid cancer (MTC) and relapse
      of Graves' disease (GD). A 26-year-old Chinese female suffered from GD for 1
      year. Physical examination demonstrated mildly diffuse goiter with a palpable 1.0
      cm nodule in the right thyroid lobe and exophthalmos. Before hemithyroidectomy,
      calcitonin was elevated and thyroglobulin was normal. After surgery,
      histopathological findings proved coexistence of MTC and GD. 16 months later, GD
      relapsed and radioactive iodine 131 therapy was given. Meanwhile, postoperative
      monitoring showed well controlled calcitonin and carcinoembryonic antigen. Our
      lesson demonstrates although concomitant of MTC and GD is very rare, yet after
      hemithyroidectomy for the single nodular MTC lesion, remnant thyroid lobe could
      be the source of GD relapse very soon. More importantly, the relapse of GD and
      the following radioiodine therapy and radiation exposure could have been
      prevented if a better therapy plan of total thyroidectomy was adopted in the
      first place, instead of hemithyroidectomy (Tab. 1, Fig. 2, Ref. 11).

PMID- 24020715
TI  - Celiac disease hidden by cryptogenic hypertransaminasemia mistaken for fatty
      liver.
AB  - A variety of signs and symptoms have been reported in regards to the typical and
      atypical presentations of CD. It is now well recognised that its onset may occur
      at any age and that atypical forms of CD are much more prevalent than its classic
      form (1).In this case, where the patient presented with high BMI and evidence of
      grade I of fatty liver disease, CD was suspected due to mildly abnormal bloating,
      cryptogenic hypertransaminasemia, abnormal LFT and poor response to fatty liver
      treatment. This presentation type is not uncommon; diagnosis was confirmed by the
      presence of subtotal villous atrophy in the biopsy specimen, positive specific
      antibody screening (AGA, tTG and EMA antibodies), negative antibody screening and
      normalization of liver enzymes on a gluten-free diet (Tab. 2, Ref. 13).

PMID- 24020716
TI  - Iris Flocculi as an ocular marker of ACTA2 mutation in familial thoracic aortic
      aneurysms and dissections.
AB  - Non-syndromic familial thoracic aortic aneurysms and dissections (TAAD) are
      inherited in an autosomal dominant manner. We report a missense mutation in the
      smooth muscle alpha-actin (ACTA2; MIM*102620) gene in a 3 generational family
      from Northern Ireland in which iris flocculi were an ocular marker of the
      disease.

PMID- 24020717
TI  - Efficacy of catheter ablation in nonparoxysmal atrial fibrillation patients with
      severe enlarged left atrium and its impact on left atrial structural remodeling.
AB  - INTRODUCTION: The effect of catheter ablation on severe left atrial enlargement
      especially in nonparoxysmal atrial fibrillation (NPAF) patients is not well
      understood. Whether reverse remodelling may occur after ablation has not been
      evaluated in this setting. METHODS AND RESULTS: Fifty consecutive patients with
      left atrial diameter (LAD) >=50 mm, and LA volume >200 cc undergoing catheter
      ablation for drug-refractory NPAF were included in this study. Transthoracic
      echocardiographic measurements were performed at baseline and at 12-months
      postprocedure. Left ventricular end-diastolic and end-systolic dimensions were
      indexed by body surface area (LVEDDI, LVESDI). Electroanatomic mapping system
      (Carto or NavX system) and computed tomography (CT) were used for 3-dimensional
      reconstruction of the LA. All patients underwent posterior wall isolation and
      pulmonary vein (PV) antrum and extra PV trigger ablations. Long-term follow-up
      was monitored by event recordings, 7-day Holter monitors and office visits. The
      mean age was 65 +/- 10 years, 78% male, persistent AF 22 (44%), longstanding AF
      28 (56%), LAD diameter 56.9 +/- 7.8 mm, left ventricular ejection fraction (LVEF)
      53 +/- 14 and median AF duration 72 (49-96) months. At 12-month follow-up, 27
      patients (54%) remained arrhythmia-free off antiarrhythmic drugs. Significant
      reduction in LAD at follow-up (>=10% reduction) was observed in 52% (26/50) of
      the total population and among the 63% (17/27) of recurrence-free patients.
      Magnitude of LA reduction was identically distributed among the persistent and
      longstanding persistent AF cohorts (16 +/- 12% vs 14 +/- 16%, respectively, P =
      0.15). A significant 20% improvement in LVEF (from 53 +/- 14 to 58 +/- 9, P =
      0.03) was found in the overall population. Improvement was noted in recurrence
      free patients. No significant change in LVEDDI and LVESDI was noted. After
      adjusting for baseline risk factors in a multivariable model, a reduction in LAD
      was identified as a strong predictor of long-term success (beta = -11.1, P =
      0.013). Preexisting LA scarring was associated with increased LAD (beta = 2.7, P
      = 0.023). No periprocedural or long-term complications were reported. CONCLUSION:
      Our results show that atrial fibrillation ablation is effective in NPAF patients
      with severe LA enlargement and is associated with LA reverse remodeling and
      improvement in LVEF.

PMID- 24020718
TI  - Oxidative stress injury after on-pump cardiac surgery: effects of aortic cross
      clamp time and type of surgery.
AB  - BACKGROUND: Cardiopulmonary bypass (CPB) in on-pump cardiac surgery can have
      harmful systemic effects, triggered in part by radical oxygen species (ROS)
      produced by ischemia-reperfusion in the heart and the lung. We determined the
      relationship between levels of oxidative stress markers (8-isoprostane and
      nitrites/nitrates) in plasma with aortic cross clamp duration in patients
      undergoing cardiac surgery with CPB. METHODS: Thirty patients with CPB were
      studied: 14 with coronary artery bypass graft surgery and 16 with valve surgery.
      Plasma levels of 8-isoprostane, and nitrites/nitrates were measured over a 24
      hour time course: before (T0) and after CPB: 5 minutes (T1), 1 hour (T2), 12
      hours (T3), and 24 hours (T4). RESULTS: Plasma levels of 8-isoprostane and
      nitrites/nitrates increased early after CPB, with a subsequent and progressive
      decline. Levels of oxidative stress markers in T1-T2 were positively correlated
      with the aortic cross clamp duration. Aortic cross clamp duration times greater
      than 50 minutes were correlated with higher oxidative stress levels. There were
      no significant differences in the levels of oxidative stress markers between
      surgery types. CONCLUSION: Cardiac surgery with CPB is associated with an early
      increase of oxidative stress markers in systemic blood. Aortic cross clamp
      duration is positively correlated with oxidative stress injury.

PMID- 24020719
TI  - Evaluation of systemic oxidant/antioxidant status and paraoxonase 1 enzyme
      activities in psoriatic patients treated by narrow band ultraviolet B
      phototherapy.
AB  - OBJECTIVES: Ultraviolet B is a potent oxidative stress (OS) inducer in the skin;
      however, there are no data about the systemic oxidative effect of narrow band
      ultraviolet B (NB-UVB) phototherapy. In this study, we aimed to investigate the
      change in the OS status of psoriatic patients who were treated by NB-UVB
      phototherapy and to determine the relationships between OS, psoriasis severity,
      and systemic inflammatory condition. METHODS: Twenty-four psoriatic patients were
      treated with a total of 30 sessions of NB-UVB irradiation. Psoriasis area and
      severity index (PASI), serum levels of high sensitive C-reactive protein (hsCRP),
      total antioxidant status (TAS), total oxidant status (TOS), the oxidative stress
      index (OSI), serum paraoxonase (PON), and arylesterase (ARE) activities before
      and after NB-UVB therapy were determined. RESULTS: PASI scores significantly
      decreased after NB-UVB therapy (P = 0.001). The pre- and post-treatment hsCRP and
      TAS levels were similar (P = 0.253 and 0.301, respectively). TOS and OSI values
      significantly increased after phototherapy (both P < 0.001). PON and ARE
      activities did not change after treatment (both P > 0.05). There was no
      correlation between PASI and hsCRP, TAS, TOS, OSI, PON, and ARE values (P >
      0.05). CONCLUSION: A systemic OS may emerge in psoriatic patients treated by NB
      UVB phototherapy.

PMID- 24020720
TI  - One-electron oxidation of antioxidants: a kinetic-thermodynamic correlation.
AB  - The values of the bimolecular rate constants for the reactions of 2,2'-azino
      bis(3-ethylbenz-thiazoline-6-sulfonic acid) radical cation with epicatechin
      (((2.4 +/- 0.2)) s(-1) M(-1)), and epigallocatechingallate ((29 +/- 5) s(-1) M(
      1)) were obtained by spectrophotometric measurements. We propose a correlation
      between the Gibbs energy DeltaG(o) for the one-electron charge-transfer reactions
      from several antioxidants to radical species and the rate constants of the
      corresponding bimolecular reactions. This correlation can be used to predict rate
      constants of reactions of known DeltaG(o) values. 

PMID- 24020721
TI  - Preparation of dye-adsorbing ZnO thin films by electroless deposition and their
      photoelectrochemical properties.
AB  - Dye-adsorbing ZnO thin films were prepared on ITO films by electroless
      deposition. The films were formed in an aqueous solution containing zinc nitrate,
      dimethylamine-borane, and eosin Y at 328 K. The film thickness was 1.2-2.0 MUm.
      Thinner and larger-plane hexagonal columns were produced from the solution
      containing a higher concentration of eosin Y. A photocurrent was observed in the
      electrodes containing such ZnO films during light irradiation. The
      photoelectrochemical performance of the film was improved by increasing the
      concentration of eosin Y because of increases in the amount of absorbed photons
      and the electronic conductivity of ZnO. 

PMID- 24020722
TI  - Influence of prosthetic parameters on peri-implant bone resorption in the first
      year of loading: a multi-factorial analysis.
AB  - BACKGROUND: The first year of prosthetic loading is crucial to peri-implant bone
      levels; however, contributing factors are yet barely understood. PURPOSE: The
      purpose of the study is to investigate the influence of patient-, implant-, and
      prosthetic-related parameters on marginal bone resorption in partially edentulous
      patients within the first year of prosthetic loading. MATERIALS AND METHODS: This
      retrospective multifactorial analysis involved the following influencing factors:
      patient gender and age, implant diameter, implant location and neck design,
      insertion torque, insertion depth, splinted versus single-tooth restorations,
      crown height space, and crown-to-implant ratio. RESULTS: Mean peri-implant bone
      resorption around 200 dental implants was 0.98 +/- 0.76 mm and significantly
      correlated to higher implant insertion depth (p < .001), whereas no association
      to prosthetic parameters could be observed. CONCLUSIONS: Within the limits of the
      present analysis, it can be concluded that apical implant positioning may
      constitute a relevant determinant of early peri-implant bone resorption.

PMID- 24020723
TI  - Identification of drought stress-responsive transcription factors in ramie
      (Boehmeria nivea L. Gaud).
AB  - BACKGROUND: Ramie fiber extracted from stem bark is one of the most important
      natural fibers. Drought is a main environment stress which severely inhibits the
      stem growth of ramie and leads to a decrease of the fiber yield. The drought
      stress-regulatory mechanism of ramie is poorly understood. RESULT: Using Illumina
      sequencing, approximately 4.8 and 4.7 million (M) 21-nt cDNA tags were
      respectively sequenced in the cDNA libraries derived from the drought-stressed
      ramie (DS) and the control ramie under well water condition (CO). The tags
      generated from the two libraries were aligned with ramie transcriptome to
      annotate their function and a total of 23,912 and 22,826 ramie genes were matched
      by these tags of DS and CO library, respectively. Comparison of gene expression
      level between CO and DS ramie based on the differences of tag frequencies
      appearing in the two libraries revealed that there were 1516 potential drought
      stress-responsive genes, in which 24 genes function as transcription factor (TF).
      Among these 24 TFs, the unigene19721 encoding the DELLA protein which is a key
      negative regulator in gibberellins (GAs) signal pathway was probably markedly up
      regulated under water stress for a increase of tag abundance in DS library, which
      is possibly responsible for the inhibition of the growth of drought-stressed
      ramie. In order to validate the change of expression of these potential stress
      responsive TFs under water deficit condition, the unigene19721 and another eleven
      potential stress-responsive TFs were chosen for further expression analysis in
      well-watered and drought-stressed ramie by real-time quantitative PCR (qRT-PCR)
      and the result showed that all 12 TFs were authentically involved in the response
      of drought stress. CONCLUSION: In this study, twelve TFs involving in the
      response of drought stress were first found by Illumina tag-sequencing and qRT
      PCR in ramie. The discovery of these drought stress-responsive TFs will be
      helpful for further understanding the drought stress-regulatory mechanism of
      ramie and improving the drought tolerance ability of ramie.

PMID- 24020724
TI  - High-risk human papillomavirus load and biomarkers in cervical intraepithelial
      neoplasia and cancer.
AB  - The purpose of this study was to examine the implication of high-risk human
      papillomavirus (HPV) load in cervical intraepithelial neoplasia (CIN) and cancer,
      and to detect biomarkers in cervical disease. We conducted high-risk HPV DNA load
      and cervical cytology tests in 343 women, cervical tissue biopsy in 143 women,
      and immunohistochemistry for p16(INK4A), cyclin D1, p53, cyclooxygenase-2, Ki-67,
      GLUT1, hPygopus2, and beta-catenin. As a result, HPV load [relative light units
      (RLU) value] was correlated with the histological severity of cervical disease (p
      < 0.05). In the 'atypical squamous cells of undetermined significance' cytology
      group, 2.385 of HPV load seemed to be the cut-off value at which 'benign' or CIN
      I can be differentiated from 'CIN II or more severe' (AUC = 0.712), but not
      statistically significant. The relative risk (odds ratio) of p16(INK4A) and GLUT1
      overexpression increased gradually according to the histological severity of
      cervical disease. The p16(INK4A) showed statistically significant odds ratios in
      CIN II, CIN III, and cancer; GLUT1, in CIN II and CIN III; hPygopus2, in CIN III;
      and beta-catenin, in CIN III and cancer. Conclusively, HPV load, p16(INK4A) , and
      GLUT1 can be instrumental in predicting the severity of HPV-related cervical
      disease. The beta-catenin/hPygopus2 signaling may be involved in proceeding to
      CIN III.

PMID- 24020725
TI  - Oxidation of CO and NO on composition-selected cerium oxide cluster cations.
AB  - The collisional reactions of composition-selected cerium oxide cluster cations,
      CenOm(+) (n = 2-6; m <= 2n), with CO and NO have been investigated under single
      collision conditions using a tandem mass spectrometer. At near-thermal energy,
      oxidation of CO and NO is observed only for the stoichiometric clusters,
      CenO2n(+) (n = 3-5), and the cross sections for the NO oxidation are found to be
      larger than those for the CO oxidation. In addition, the collision-energy
      dependence of the reaction cross sections reveals that the CO oxidation has a
      small activation barrier, whereas the NO oxidation is a barrierless process.
      These experimental findings are supported by density functional theory
      calculations. 

PMID- 24020726
TI  - Fine central macular dots associated with childhood-onset Stargardt Disease.

PMID- 24020727
TI  - Toward tunable adsorption properties, structure, and crystallinity of titania
      obtained by block copolymer and scaffold-assisted templating.
AB  - Nanostructured titania and composite titania materials were synthesized for the
      first time by a one-pot strategy in an aqueous solution containing Pluronic P123
      block copolymer and suitable precursors. The strategy can be considered as more
      facile, environmentally friendly, and less expensive as compared to the existing
      ones that require use of organic solvents. In the case of composites, silica and
      alumina particles were used as a structure protecting scaffold and composite
      components. This synthesis strategy allowed tuning of adsorption and structural
      properties of the resulting materials; namely, the specific surface area was
      varied from 84 to 250 m(2) g(-1), total pore volume from 0.11 to 0.46 cm(3) g(
      1), and the pore width from 5.6 to 11.2 nm. All samples studied but one showed
      exclusively anatase phase, and the composites obtained with silica scaffold
      showed tunable degree of crystallinity. The proposed approach to tailoring the
      surface and structure properties of titania is especially important for the
      development of high performance materials for photocatalysis, lithium-based
      batteries, and dye-sensitized solar cells. 

PMID- 24020728
TI  - Test-retest reliability of the 'Reading the Mind in the Eyes' test: a one-year
      follow-up study.
AB  - BACKGROUND: The 'Reading the Mind in the Eyes' (Eyes) test is an advanced test of
      theory of mind. It is widely used to assess individual differences in social
      cognition and emotion recognition across different groups and cultures. The
      present study examined distributions of responses and scores on a Spanish version
      of the test in a non-clinical Spanish adult population, and assessed test-retest
      reliability over a 1-year interval. METHODS: A total of 358 undergraduates of
      both sexes, age 18 to 65 years, completed the Spanish version of the test twice
      over an interval of 1 year. The Bland-Altman method was used to calculate test
      retest reliability. RESULTS: Distributions of responses and scores were optimal.
      Test-retest reliability for total score on the Eyes test was .63 (P <.01), based
      on the intraclass correlation coefficient. Test-retest reliability using the
      Bland-Altman method was fairly good. CONCLUSIONS: This is the first study
      providing evidence that the Eyes test is reliable and stable over a 1-year
      period, in a non-clinical sample of adults.

PMID- 24020729
TI  - Predictors of antenatal depression among Jordanian pregnant women in their third
      trimester.
AB  - Antenatal depression has not been well studied worldwide. The objective of this
      study was to identify the prevalence and predictors of antenatal depression among
      Jordanian pregnant women in their third trimester. A correlational design was
      used with a convenience sample of 218 Jordanian pregnant women. Data were
      collected using valid and reliable measures and were analyzed with regression.
      Fifty-seven percent of the women displayed symptoms of depression. Thirty-seven
      percent (34% adjusted) of the variability in depression levels was predicted by
      knowing scores on life satisfaction, perceived stress, family and nonfamily
      stressful relationships, education, and parity. For that, antenatal depression
      needs early detection and treatment. 

PMID- 24020730
TI  - Scale development on consumer behavior toward counterfeit drugs in a developing
      country: a quantitative study exploiting the tools of an evolving paradigm.
AB  - BACKGROUND: Although desperate need and drug counterfeiting are linked in
      developing countries, little research has been carried out to address this link,
      and there is a lack of proper tools and methodology. This study addresses the
      need for a new methodological approach by developing a scale to aid in
      understanding the demand side of drug counterfeiting in a developing country.
      METHODS: The study presents a quantitative, non-representative survey conducted
      in Sudan. A face-to-face structured interview survey methodology was employed to
      collect the data from the general population (people in the street) in two
      phases: pilot (n = 100) and final survey (n = 1003). Data were analyzed by
      examining means, variances, squared multiple correlations, item-to-total
      correlations, and the results of an exploratory factor analysis and a
      confirmatory factor analysis. RESULTS: As an approach to scale purification,
      internal consistency was examined and improved. The scale was reduced from 44 to
      41 items and Cronbach's alpha improved from 0.818 to 0.862. Finally, scale items
      were assessed. The result was an eleven-factor solution. Convergent and
      discriminant validity were demonstrated. CONCLUSION: The results of this study
      indicate that the "Consumer Behavior Toward Counterfeit Drugs Scale" is a valid,
      reliable measure with a solid theoretical base. Ultimately, the study offers
      public health policymakers a valid measurement tool and, consequently, a new
      methodological approach with which to build a better understanding of the demand
      side of counterfeit drugs and to develop more effective strategies to combat the
      problem.

PMID- 24020731
TI  - What strategies are in place to control microbial burden in hospital environments
      and how could these change in the future?

PMID- 24020732
TI  - Listen to your patient: women often know if they have a urinary tract infection.

PMID- 24020734
TI  - Meeting the challenge of invasive fungal infections: part 1.
AB  - The European Congress of Clinical Microbiology and Infectious Diseases (ECCMID),
      the annual meeting of the European Society of Clinical Microbiology and
      Infectious Diseases, is now the world's largest conference on infectious
      diseases. This year, the meeting attracted a global attendance of more than
      10,000 scientists and clinicians to share state-of-the-art information on
      infectious diseases. This article, the first of a two-part report on the ECCMID
      2013 conference, reviews sessions on the increasing challenges and emerging new
      threats from invasive fungal infections. 

PMID- 24020735
TI  - Interview by Hannah Branch: microbes in the mouth: an insider's view.
AB  - Nick Jakubovics speaks to Hannah Branch, Commissioning Editor Nick Jakubovics
      attended the University of Cambridge (UK) where he obtained a BSc in
      Biochemistry, which was followed by the completion of a PhD in Microbiology at
      the University of Warwick (UK). In 1998, he became a postdoctoral researcher at
      Bristol Dental School (UK) in the laboratory of Howard Jenkinson. In 2004,
      Jakubovics obtained a NIH postdoctoral fellowship to work at the National
      Institute for Dental and Craniofacial Research (MD, USA) in the laboratory of
      Paul Kolenbrander. Following this, in 2007, he became a Lecturer in Oral
      Microbiology at Newcastle Dental School (UK). His research is focused on
      understanding the role of the extracellular matrix in biofilms with an
      overarching aim of developing methods to control biofilms. Jakubovics is a member
      of the Society for General Microbiology and Executive Committee of the Society
      for Applied Microbiology. 

PMID- 24020736
TI  - TMC207 becomes bedaquiline, a new anti-TB drug.
AB  - TB still represents a serious public health problem. The latest reports estimate
      an incidence of 8.7 million cases in 2011 and 1.4 million deaths. Drug resistance
      contributed an estimated 630,000 cases of multidrug-resistant TB, making control
      of the disease harder. Recent reports show cases of TB that were almost resistant
      to all available antibiotics. Therefore, there is an urgent need to develop new
      anti-TB drugs with the potential of reducing the current length of treatment.
      Bedaquiline, formerly TMC207, is a new diarylquinoline antibiotic with specific
      activity against Mycobacterium tuberculosis and several nontuberculous
      mycobacteria. It acts by inhibiting ATP synthase, interfering with the energy
      generation needed by the bacterial cell. Based on clinical evaluations for
      safety, tolerability and efficacy, bedaquiline has recently received accelerated
      approval for the treatment of pulmonary multidrug-resistant TB in adults. This
      article will review the main aspects related to the chemistry, microbiology,
      pharmacology, efficacy and tolerability of bedaquiline. 

PMID- 24020737
TI  - Radioimmunotherapy of Cryptococcus neoformans spares bystander mammalian cells.
AB  - AIM: Previously, we showed that radioimmunotherapy (RIT) for cryptococcal
      infections using radioactively labeled antibodies recognizing the cryptococcal
      capsule reduced fungal burden and prolonged survival of mice infected with
      Cryptococcus neoformans. Here, we investigate the effects of RIT on bystander
      mammalian cells. MATERIALS & METHODS: Heat-killed C. neoformans bound to
      anticapsular antibodies, unlabeled or labeled with the beta-emitter rhenium-188
      (16.9-h half-life) or the alpha-emitter bismuth-213 (46-min half-life), was
      incubated with macrophage-like J774.16 cells or epithelial-like Chinese hamster
      ovary cells. Lactate dehydrogenase activity, crystal violet uptake, reduction of
      tetrazolium dye (2,3)-bis-(2-methoxy-4-nitro-5-sulfenyl)-(2H)-terazolium-5
      carboxanilide and nitric oxide production were measured. RESULTS: The J774.16 and
      Chinese hamster ovary cells maintained membrane integrity, viability and
      metabolic activity following exposure to radiolabeled C. neoformans. CONCLUSION:
      RIT of C. neoformans is a selective therapy with minimal effects on host cells
      and these results are consistent with observations that RIT-treated mice with
      cryptococcal infection lacked RIT-related pathological changes in lungs and brain
      tissues.

PMID- 24020738
TI  - Contact-free inactivation of Trichophyton rubrum and Microsporum canis by cold
      atmospheric plasma treatment.
AB  - AIM: Cold atmospheric plasma (CAP) has already proven efficient at disinfection
      of microorganisms including biofilms. The objective of the present study is to
      assess the efficacy of CAP against the dermatophytes Trichophyton rubrum and
      Microsporum canis in vitro. MATERIALS & METHODS: T. rubrum and M. canis were
      exposed to CAP for different treatment times and time intervals in vitro.
      Treatment with ciclopirox olamine or UVC radiation (0.120 J/cm(2)) served as
      controls. CAP was generated by the surface microdischarge technology. Fungal
      colony growth was measured upon CAP treatment. RESULTS: Repeated daily CAP
      treatments of 10 min demonstrated an inhibition of growth during the treatment
      period of 9 days. Single CAP treatment sessions for 5, 8 and 10 min, as well as
      treatments for 5 or 8 min daily, resulted in less fungal growth inhibition. UVC
      radiation treatment failed, but not ciclopirox olamine. CONCLUSION: CAP shows
      promising potential for future application in the treatment of dermatophyte
      infections.

PMID- 24020739
TI  - Elucidating the immunological function of the Cryptococcus neoformans capsule.
AB  - The encapsulated fungal pathogen Cryptococcus neoformans represents a significant
      agent of life-threatening infections in immunocompromised subjects. A unique
      characteristic of Cryptococcus species is the presence of a polysaccharide
      capsule, which is essential for virulence and endows Cryptococcus with potent
      immunoregulatory properties. This review provides an overview of the
      immunological properties of the principal components of C. neoformans capsule. 

PMID- 24020740
TI  - Natural history of Bartonella-infecting rodents in light of new knowledge on
      genomics, diversity and evolution.
AB  - Among the 33 confirmed Bartonella species to date, more than half are hosted by
      rodent species, and at least five of them have been involved in human illness
      causing diverse symptoms including fever, myocarditis, endocarditis,
      lymphadenitis and hepatitis. In almost all countries, wild rodents are infected
      by extremely diverse Bartonella strains with a high prevalence. In the present
      paper, in light of new knowledge on rodent-adapted Bartonella species genomics,
      we bring together knowledge gained in recent years to have an overview of the
      impact of rodent-adapted Bartonella infection on humans and to determine how
      diversity of Bartonella helps to understand their mechanisms of adaptation to
      rodents and the consequences on human health. 

PMID- 24020742
TI  - Confronting carbapenemase-producing Klebsiella pneumoniae.
AB  - The ongoing spread of carbapenemase-producing (CP) multidrug-resistant
      enterobacteria, primarily Klebsiella pneumoniae, has undoubtedly caused a public
      health crisis of unprecedented dimensions. The scientific community has been
      struggling with these highly problematic nosocomial pathogens for more than a
      decade. Faced with the current situation, one cannot help but wish we could have
      done better, earlier. However, significant steps have been and are currently
      being made towards a better understanding of transmission routes of CP
      microorganisms and in designing strategies that could effectively curb this
      devastating epidemic. Most importantly, the systematic evaluation of accumulating
      experimental and clinical data has paved the way to a more rational management of
      CP-infected patients. In addition, systematic efforts of the industry have led to
      the development of novel antibacterial agents that are active against CP strains
      and expected to be introduced to clinical practice in the immediate future. 

PMID- 24020743
TI  - Epidemiology and treatment of mucormycosis.
AB  - Mucormycosis is an uncommon but aggressive opportunistic fungal infection that
      afflicts patients with severe underlying immunosuppression, uncontrolled
      hyperglycemia and/or ketoacidosis, patients with iron overload resulting from
      frequent blood transfusions or blood disorders and occasionally healthy patients
      who are inoculated with fungal spores through traumatic injuries. The clinical
      presentation of mucormycosis is initially indistinguishable from other common
      infections, and if not diagnosed early and aggressively treated, it is almost
      always fatal. In this article we summarize recent changes in the epidemiology of
      mucormycosis, discuss diagnostic and clinical clues suggestive of the infection
      and provide a general strategy for managing the infection in the absence of data
      from well-controlled, prospective clinical trials. 

PMID- 24020741
TI  - Genetic variation in Chlamydia trachomatis and their hosts: impact on disease
      severity and tissue tropism.
AB  - Chlamydia trachomatis infections are a global health problem. This obligate
      intracellular bacterial pathogen comprises lymphogranuloma venereum (L1-L3),
      ocular (A-C) and genital (D-K) serovars. Although genetically similar, each
      serovar group differs in disease severity and tissue tropism through mechanisms
      that are not well understood. It is clear that host genetic differences also play
      a role in chlamydial disease outcome and key host polymorphisms are beginning to
      emerge from both human and experimental animal studies. In this review, we will
      highlight pathogen and host genes that link genetic diversity, disease severity
      and tissue tropism. We will also use this information to provide new insights
      that may be helpful in developing improved management strategies for these
      important pathogens. 

PMID- 24020744
TI  - Paracoccidioidomycosis: eco-epidemiology, taxonomy and clinical and therapeutic
      issues.
AB  - Acquired by inhalation of the thermal dimorphic fungi Paracoccidioides spp.
      conidia, paracoccidioidomycosis ranges from symptomatic to severe and potentially
      fatal disseminated disease. The main focus of this review is to highlight
      clinical aspects of paracoccidioidomycosis and, its pathogens' diversity ecology
      and particularities. In addition, we present strategies for therapy, including
      DNA vaccines and nanostructured drugs. Molecular and morphological data supported
      the split of the Paracoccidioides genus into two species, Paracoccidioides
      brasiliensis and Paracoccidioides lutzii. An acute form of the disease affects
      approximately 5% of cases and involves the phagocytic mononuclear system,
      resulting in progressive lymphadenopathy. The chronic form affects adult men and
      frequently involves lungs, skin and mucous membranes, lymph nodes, and adrenal
      glands. The clinical manifestations depend on the ability of the host to control
      the fungal multiplication and dissemination. The long survival time of the fungus
      in the host tissues allows it to evade immune responses; therefore, successful
      treatment often requires long-time therapy. The consensus for treatment must
      consider the severity of the disease and includes sulfone derivatives,
      amphotericin B and azoles. Novel strategies for therapy, based on DNA vaccines
      and nanostructured drugs are also presented and discussed in this review. 

PMID- 24020745
TI  - Regulation of virulence in Brucella: an eclectic repertoire of transcription
      factors defines the complex architecture of the virB promoter.
AB  - Many intracellular bacterial pathogens use type IV secretion systems to deliver
      effector molecules and subvert the eukaryotic host cell defenses. The genus
      Brucella comprises facultative intracellular bacteria that cause brucellosis, a
      disease affecting a wide range of mammals including humans. The virB operon codes
      for a type IV secretion system that plays a central role in intracellular
      survival and replication of Brucella within the host. Expression of the virB
      genes is under the control of various transcription factors that allow this
      system to respond to different types of environmental signals, and display
      binding site structures and arrangements that define the intrinsic complexity of
      the virB promoter. This review focuses on summarizing the current state of
      research concerning regulation of the Brucella virB operon, with special emphasis
      on describing the nature and function of the implicated regulatory elements and
      examining the involved protein-DNA interactions. 

PMID- 24020746
TI  - Avian influenza: virology, diagnosis and surveillance.
AB  - Avian influenza virus (AIV) is the causative agent of a zoonotic disease that
      affects populations worldwide with often devastating economic and health
      consequences. Most AIV subtypes cause little or no disease in waterfowl, but
      outbreaks in poultry can be associated with high mortality. Although transmission
      of AIV to humans occurs rarely and is strain dependent, the virus has the ability
      to mutate or reassort into a form that triggers a life-threatening infection. The
      constant emergence of new influenza strains makes it particularly challenging to
      predict the behavior, spread, virulence or potential for human-to-human
      transmission. Because it is difficult to anticipate which viral strain or what
      location will initiate the next pandemic, it is difficult to prepare for that
      event. However, rigorous implementation of biosecurity, vaccination and education
      programs can minimize the threat of AIV. Global surveillance programs help record
      and identify newly evolving and potentially pandemic strains harbored by the
      reservoir host. 

PMID- 24020748
TI  - Heterogeneous catalytic activity of platinum nanoparticles hosted in mesoporous
      silica thin films modified with polyelectrolyte brushes.
AB  - Platinum nanoparticles of 3 nm diameter were included in mesoporous silica thin
      films by controlling the mesopore surface charge with a short polymer brush. This
      metal-polymer-mesopore nanocomposite presents high catalytic activity toward
      ammonia oxidation at low temperatures with 4.5% weight platinum loading. An
      anomalous partial selectivity toward nitrous oxide is observed for the first
      time, which can be traced back to the synergy of the particles and modified
      surface. This effect opens a path toward the design of nanocomposite catalysts
      with highly controlled environments, in which the size- and function-controlled
      cavities can be tuned in order to lower the reaction barriers. 

PMID- 24020749
TI  - The impact of voluntary food fortification on micronutrient intakes and status in
      European countries: a review.
AB  - This review aims to assess the efficacy and safety of voluntary fortification as
      an option to address the occurrence of inadequate micronutrient intakes in
      population subgroups in Europe. Although legislation is harmonised across the
      European Union, fortification practices and patterns of consumption of fortified
      foods vary considerably between countries. While the proportion of children
      consuming fortified foods is greater than adults, the proportion of dietary
      energy obtained from fortified foods is generally low (<10% in Ireland, where
      fortified foods are widely consumed). There are a few systematic studies on the
      overall nutritional impact of voluntary fortification, but there are several
      studies on the impact of fortified ready-to-eat breakfast cereals. The available
      evidence indicates that voluntary fortification can reduce the risk of sub
      optimal intakes of a range of micronutrients at a population level and can also
      improve status for selected micronutrients (e.g. folate, vitamin D and
      riboflavin) in children and adults. Although concerns have been raised regarding
      the potential of food fortification to lead to unacceptably high micronutrient
      intakes, particularly for those consuming higher amounts of fortified foods, data
      from national surveys on total micronutrient intakes (including fortified foods)
      in Europe show that small proportions of the population, particularly children,
      may exceed the upper intake level (UL) for some micronutrients. The risk of
      adverse effects occurring in these individuals exceeding the UL by modest amounts
      is low. In conclusion, voluntary fortification practices have been shown to
      improve intake and status of key micronutrients in European Union population
      groups and do not contribute appreciably to risk of adverse effects.

PMID- 24020750
TI  - All-cause mortality and cardiovascular effects associated with the DPP-IV
      inhibitor sitagliptin compared with metformin, a retrospective cohort study on
      the Danish population.
AB  - AIM: We performed a retrospective cohort study, investigating the clinical
      outcomes including mortality and cardiovascular disease of sitagliptin compared
      with metformin monotherapies. METHODS: All patients receiving monotherapy with
      the dipeptidyl peptidase-IV inhibitors (DPP-IV) inhibitor sitagliptin between 1
      January 2007 and 31 December 2011 were identified. All-cause mortality and a
      composite endpoint of stroke, acute myocardial infarction (AMI) and all-cause
      mortality associated with sitagliptin monotherapy were compared with metformin
      monotherapy. In addition, as an indicator of efficacy we analysed the hazard
      ratio of changing treatment. RESULTS: A total of 84 756 patients were included in
      the analysis, 1228 (1.4%) received sitagliptin monotherapy whereas the remaining
      83 528 (98.6%) patients received metformin monotherapy. Patients using metformin
      were younger than patients using sitagliptin (59.0 +/- 15.2 vs. 62.5 +/- 13.1)
      were less often male (51.6 vs. 54.2%) and had longer treatment duration with
      monotherapy (1.8 +/- 1.3 vs. 0.9 +/- 1.1 years). Compared with patients receiving
      metformin, patients using sitagliptin showed no statistically significant excess
      risks of all-cause mortality [hazard ratio, 1.25; 95% confidence interval (CI),
      0.92-1.71; p = 0.153] or the composite endpoint (hazard ratio, 1.22; 95% CI, 0.92
      1.61; p = 0.164). However, the use of sitagliptin monotherapy was associated with
      an increased likelihood of changing treatment (hazard ratio, 4.88; 95% CI, 4.46
      5.35; p < 0.001). CONCLUSION: In a retrospective analysis, sitagliptin
      monotherapy compared with metformin monotherapy was not associated with any
      statistical significant increased risk of all-cause mortality or the composite
      endpoint, but was associated with an increased likelihood of changing glucose
      lowering treatment.

PMID- 24020751
TI  - Task partitioning effects in semi-automated human-machine system performance.
AB  - Twelve professional pilots performed a flight simulation consisting of three
      component sub-tasks: (i) tracking, (ii) monitoring and (iii) targeting,
      respectively. The targeting sub-task required (i) target identification, (ii)
      weapon selection and then (iii) weapon release. Pilots performed in a fully
      manual condition, a partial automation condition or a fully automated condition.
      Automated assistance was provided for the targeting sub-task only, while tracking
      and monitoring sub-tasks were always performed manually. During full automation,
      the computer located the target, identified it and released the appropriate
      weapon without any pilot input. During partial automation, the computer located
      and identified the target while the pilot retained final control over weapon
      release. Significantly higher levels of tracking error distinguished manual from
      both automated conditions and also between the two levels of automation.
      Monitoring response times were also sensitive to the degree of automation
      engaged, with the partial-automation condition exhibiting faster responses than
      full automation. Findings support a design principle in which pilots retain
      control over final weapons release directly on the basis of objective performance
      outcome. These collective results support the contention that effective and
      principled task-partitioning should represent a central strategy for the
      evolution of complex human-machine systems. PRACTITIONER SUMMARY: Advantages of
      partitioning tasks between human and automated control are contingent upon the
      overall context of performance and the actual way the partitioning is
      accomplished. Simple algorithms, for example, automate on every feasible
      occasion, are poor design heuristics and may even prove actively harmful to
      overall response capacity. Transitioning humans from active controllers to
      passive monitors can be a problematic design choice, especially when that
      individual is socially deemed to retain overall responsibility for ultimate
      system effects in the real world.

PMID- 24020752
TI  - OsFIE2 plays an essential role in the regulation of rice vegetative and
      reproductive development.
AB  - Polycomb group (PcG) proteins are gene repressors that help to maintain cellular
      identity during development via chromatin remodeling. Fertilization-independent
      endosperm (FIE), a member of the PcG complex, operates extensively in plant
      development, but its role in rice has not been fully investigated to date. We
      report the isolation and characterization of a PcG member in rice, which was
      designated OsFIE2 for Oryza sativa Fertilization-Independent Endosperm 2. OsFIE2
      is a single-copy gene in the rice genome and shows a universal expression
      pattern. The OsFIE2 RNAi lines displayed pleiotropic phenotypes in vegetative and
      reproductive organ generation. In unfertilized lines, endosperm formation could
      be triggered without embryo formation, which indicates that FIE is indeed
      involved in the suppression of autonomous endosperm development in rice.
      Furthermore, lateral root generation was promoted early in the roots of OsFIE2
      RNAi lines, whereas the primary root was premature and highly differentiated. As
      the root tip stem cell differentiated, QHB, the gene required for stem cell
      maintenance in the quiescent center, was down-regulated. Our data suggest that
      the OsFIE2-PcG complex is vital for rice reproduction and endosperm formation.
      Its role in stem cell maintenance suggests that the gene is functionally
      conserved in plants as well as animals. 

PMID- 24020753
TI  - How accurate are diagnostic tools for Epstein-Barr virus (EBV) to establish
      causal association of an uncommon clinical condition with EBV?
AB  - Epstein-Barr virus (EBV) infection has been implicated as a possible cause of a
      wide range of clinical conditions in children and young adults. In uncommon
      clinical conditions, where clinical experience is missing, it is important to
      evaluate both the biological plausibility and the virological basis that
      substantiates their causal association with EBV. By reviewing the diagnostic
      procedures performed in the diagnosis of EBV infection in case reports concerning
      uncommon clinical conditions causally related to EBV infection in children and
      young adults, the aim of the present study was to discuss the limitations of the
      diagnostic procedure used to establish EBV diagnosis, which may cause false
      positive results and compromise the reliability of such a diagnosis. We should be
      aware not only of the nuances of serological tests and virus detection tests for
      latent viruses such as EBV, but also of the risk of using them alone or in
      combination with molecular methods as the sole mean for establishing a causal
      relation between EBV infection and an uncommon clinical condition. Accurate
      laboratory tests for EBV detection, strict criteria for EBV infection diagnosis,
      and a cumulative clinical experience coupled with biological plausibility and
      experimental data are needed to avoid a possible coincidental association between
      several clinical manifestations, mainly uncommon clinical conditions, and EBV
      infection. KEYWORDS: Epstein-Barr virus; diagnostics; uncommon condition.

PMID- 24020754
TI  - How can viruses influence the neuroinflammation and neurodegeneration in the aged
      human brain.
AB  - Age is one of the key risk factors of several human neurodegenerative disorders
      such as Alzheimer?s disease and Parkinson?s disease. During aging the immune
      system of the brain undergoes multiple structural and functional changes. The
      major immune cells of the brain - microglia and astrocytes - significantly change
      their morphology and functional state during aging. Similarly, the blood brain
      barrier (BBB), that is considered to be the iron curtain protecting the brain
      parenchyma against invasion of the pathogens, can be influenced by aging. This
      state of altered brain immunity may lead to the increased brain vulnerability to
      viral infections, primoinfection as well as reactivation. We hypothesize that
      impairment of the brain immunity and BBB integrity can create the optimal
      condition for viral infection that can further amplify the neuroinflammation
      mediated by glial cells and neurodegeneration induced and driven by disease
      modified proteins.

PMID- 24020755
TI  - Potential roles of protein disulphide isomerase in viral infections.
AB  - Protein disulphide isomerase (PDI) family members are predominantly endoplasmic
      reticulum (ER)-bound chaperonic proteins, which have also been shown to be
      present on the cell surface. Some of them have been found to be associated with
      lipid rafts, MHC class I, and cell-signaling molecules such as signal transducer
      and activator of transcription (STAT) proteins in certain viral infections. Since
      there is evidence suggesting that PDIs have a role in the virus entry to the
      cell, they obviously play an important role in virus-host interactions and viral
      pathogenesis. In this review, we discuss potential roles of PDIs in viral
      infections, in order to disclose new antiviral therapeutic targets.

PMID- 24020756
TI  - Hepatocytes transduced with human TERT gene acquire a prolonged lifespan in
      culture and retain permissiveness to hepatitis B virus.
AB  - Hepatitis B virus (HBV) can be propagated in vitro in primary cultures of human
      hepatocytes and some stable hepatoma cell lines maintained under specific
      conditions. The lack of simple and non-neoplastic cell culture systems for HBV
      has hampered the analysis of virus life cycle and development of antiviral
      compounds. In this study, we succeeded in prolonging the lifespan of human
      hepatocytes in primary culture by transducing them with human telomerase reverse
      transcriptase (hTERT) gene. The transgenic cells expressed hTERT constitutively
      and propagated HBV up to 5x105 DNA copies/ml for 28 days.

PMID- 24020757
TI  - Molecular characterization of the receptor binding structure-activity
      relationships of influenza B virus hemagglutinin.
AB  - Selectivity of alpha2,6-linked human-like receptors by B hemagglutinin (HA) is
      yet to be fully understood. This study integrates binding data with structure
      recognition models to examine the impact of regional-specific sequence variations
      within the receptor-binding pocket on selectivity and structure activity
      relationships (SAR). The receptor-binding selectivity of influenza B HAs
      corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was
      examined using surface plasmon resonance, solid-phase ELISA and gel-capture
      assays. Our SAR data showed that the presence of asialyl sugar units is the main
      determinant of receptor preference of alpha2,6 versus alpha2,3 receptor binding.
      Changes to the type of sialyl-glycan linkage present on receptors exhibit only a
      minor effect upon binding affinity. Homology-based structural models revealed
      that structural properties within the HA pocket, such as a glyco-conjugate at
      Asn194 on the 190-helix, sterically interfere with binding to avian receptor
      analogs by blocking the exit path of the asialyl sugars. Similarly, naturally
      occurring substitutions in the C-terminal region of the 190-helix and near the N
      terminal end of the 140-loop narrows the horizontal borders of the binding
      pocket, which restricts access of the avian receptor analog LSTa. This study
      helps bridge the gap between ligand structure and receptor recognition for
      influenza B HA; and provides a consensus SAR model for the binding of human and
      avian receptor analogs to influenza B HA.

PMID- 24020758
TI  - Effects of the Q223R mutation in the hemagglutinin (HA) of egg-adapted pandemic
      2009 (H1N1) influenza A virus on virus growth and binding of HA to human- and
      avian-type cell receptors.
AB  - The 2009 swine-origin influenza A virus (H1N1) and its initial reassortant
      vaccine strains did not grow well in embryonated eggs. The glutamine to arginine
      mutation at the amino acid position 223 (Q223R) of the hemagglutinin (HA) gene is
      the major mutation previously found in egg-adapted 2009 H1N1 strains and shown to
      enhance viral growth in embryonated eggs. However, the effect of this mutation on
      the receptor-binding preference had not been directly demonstrated. In this
      study, the Q223R mutation was shown to change the viral HA binding preference
      from the human-type receptor, alpha2,6-linked sialic acid, to the avian-type
      receptor, alpha2,3-linked sialic acid; and to enhance the viral growth in
      embryonated eggs but not in cell culture.

PMID- 24020759
TI  - Primary cultures of murine neurons for studying herpes simplex virus 1 infection
      and its inhibition by antivirals.
AB  - Herpes simplex virus 1 (HSV-1) establishes life-long latency in peripheral
      neurons, where productive replication is suppressed. To study the specific
      relationship between the virus and peripheral neurons that would not be affected
      by other cells usually present in in vivo systems, we present an in vitro model
      system based on primary cultures of murine neurons. This model system can be used
      for characterization of various virus strains and testing of cytotoxicity and
      inhibitory activity of acyclovir (ACV), cidofovir (CDV) and other antivirals.

PMID- 24020760
TI  - Increased incidence of mumps in the Czech Republic in the years 2011 and 2012.
AB  - A nation-wide vaccination against mumps that had been launched in the Czech
      Republic in 1987 eliminated great outbreaks (up to 100,000 cases per year) of
      this disease in 1955-1988, but did not prevent small outbreaks (a few thousand
      cases per year) in 1995-1996, 2005-2007, and 2010-2012. The extent of these small
      outbreaks shows an increasing trend. The article describes mumps outbreaks in the
      Czech Republic in 2011 and 2012 with the aim to bring additional data
      contributing to the clarification of repeated outbreak triggers. In the years
      2011 and 2012 there have been reported 2885 and 3902 mumps cases, respectively,
      in the Czech Republic. Similarly to other countries, a shift in the age-specific
      incidence of the disease towards higher age has been found, with the highest
      occurrence seen in the age group of 15-19 years. Men were slightly more affected
      than women. Clinical complications and vaccination status of patients were also
      observed.

PMID- 24020761
TI  - Analysis of a short genomic region of Grapevine leafroll-associated virus 1
      (GLRaV-1) reveals the presence of two different molecular groups of isolates in
      Slovakia.
AB  - Although grapevine leafroll-associated virus 1 (GLRaV-1) is one of the most
      important agents of the grapevine leafroll disease, the data about its molecular
      variability are scarce. In order to assess the GLRaV-1 diversity in Slovakia, the
      sequence of a genome region encoding the central part of the capsid protein (CP)
      gene was determined from 18 GLRaV-1 isolates. Despite the fact that the analysis
      targeted a relatively short portion of the genome, comparison of obtained
      sequences has revealed the nucleotide identities between Slovak isolates ranging
      from 83.0-100%. Phylogenetic analysis indicated the presence of two distinct
      molecular groups of GLRaV-1 in Slovakia.

PMID- 24020762
TI  - The variability of Hosta virus X isolates in the Czech Republic.
AB  - The coat protein (CP) gene DNA sequences of nine isolates of Hosta virus X (HVX)
      from different regions of the Czech Republic were determined and compared with
      sequences available in GenBank. The sequences were almost uniform, the pairwise
      nucleotide identities among the Czech HVX isolates were 99-100%. The respective
      range was 98-100% when sequences from the GenBank were included. Therefore,
      phylogenetic analyses including Maximum parsimony and Bayesian analyses of
      either, DNA and deduced amino acid sequences, showed close relationship among
      isolates. Only the group of two isolates, HVXCR1 and HVXCR8 showed significant
      sequence divergence in phylogenetic trees. The HVXCR1-HVXCR8 group differs from
      the others by the substitution of glutamine (Q) by arginine (R). Moreover, these
      isolates showed different symptoms on infected hosta leaves - deformation on the
      leaves without a mosaic or mottling. This amino acid change may, therefore, have
      a biological significance.

PMID- 24020763
TI  - Genetic typing of porcine reproductive and respiratory syndrome virus isolates
      from central European countries.
AB  - All thirty-three but one porcine reproductive and respiratory syndrome virus
      (PRRSV) isolate originating from pigs in Austria, Czech Republic and Slovakia
      were typed on the basis of partial ORF5 sequence as PRRSV-1, subtype EU-1. The
      single isolate of PRRSV-2 originated from Slovakia.

PMID- 24020764
TI  - Plum pox virus accumulates mutations in different genome parts during a long-term
      maintenance in Prunus host plants and passage in Nicotiana benthamiana.
AB  - Plum pox virus (PPV) isolates of the strain PPV-M prevalently infect peaches
      under natural conditions in Middle Europe. Comparison of complete genome
      sequences obtained from subisolates of a PPV-M isolate maintained experimentally
      over a 6-year period in different Prunus host species and passaged in Nicotiana
      benthamiana was performed with the aim to highlight the mutations potentially
      connected with the virus-host adaptation. The results showed that the lowest
      number of non-silent mutations was accumulated in PPV-M maintained in peach
      (original host species), approximately two times higher diversity was recorded in
      plum, apricot and N. benthamiana, indicating the genetic determination of the PPV
      host preference. The sequence variability of Prunus subisolates was distributed
      more or less evenly along the PPV genome and no amino acid motif could be
      outlined as responsible for the host adaptation. In N. benthamiana the mutations
      were accumulated notably in the P1 and P3 genes indicating their non-essentiality
      in the infection of this experimental host plant.

PMID- 24020765
TI  - Efficient endotoxin removal from T7 phage preparations by a mild detergent
      treatment followed by ultrafiltration.

PMID- 24020766
TI  - Prophylaxis of human cytomegalovirus infection in renal transplant patients with
      valacyclovir and ganciclovir.

PMID- 24020767
TI  - A microneutralization assay for dengue viruses using mosquito C6/36 cells.

PMID- 24020768
TI  - Coat protein based molecular characterization of Barley yellow dwarf virus
      isolates identified on oat plants in Pakistan.
AB  - Barley yellow dwarf virus (BYDV) is a potential threat to the agriculture
      production. The amplified complete coat protein sequences of the isolate M07 and
      M12 were determined to be 597 bp and 603bp, respectively. M07 showed maximum
      nucleotide sequence identity of 87.6% (84.3% amino acid sequence identity) to a
      Chinese isolate of BYDV-PAV. Whereas, the isolate M12 showed maximum nucleotide
      sequence identity of 94.5% (94.0% amino acid sequence identity) to French isolate
      BYDV-PAV. Since more than 10 o/o differences, among the amino acid level of any
      gene product, is the sole criterion to discriminate between species within the
      family Luteoviridae, the isolate M07 that shows maximum of 84.3% (less than 90%)
      amino acid sequence identity with previously known Luteovirus species, is thus,
      recommended to be a distinct PAV species within the genus Luteovirus.

PMID- 24020769
TI  - Intraspecific 16S rRNA gene diversity among clinical isolates of Neisseria
      species.
AB  - In the present work, nearly the entire 16S rRNA gene sequences of 46 clinical
      samples of Neisseria spp. were determined, and the aligned sequences were
      analyzed to investigate the diversity of 16S rRNA genes in each commensal
      Neisseria species. Two 16S rRNA types were identified in two Neisseria sicca
      strains, three 16S rRNA types in five Neisseria macacae strains, fourteen 16S
      rRNA types in twenty Neisseria flavescens isolates, and fourteen 16S rRNA types
      in nineteen Neisseria mucosa isolates. The number of nucleotides that were
      different between 16S rRNA sequences within specie ranged from 1 to 15. We found
      high intraspecific sequence variation in 16S rRNA genes of Neisseria spp.
      strains.

PMID- 24020770
TI  - Structural optimization of quinolon-4(1H)-imines as dual-stage antimalarials:
      toward increased potency and metabolic stability.
AB  - Discovery of novel effective and safe antimalarials has been traditionally
      focused on targeting erythrocytic parasite stages that cause clinical symptoms.
      However, elimination of malaria parasites from the human population will be
      facilitated by intervention at different life-cycle stages of the parasite,
      including the obligatory developmental phase in the liver, which precedes the
      erythrocytic stage. We have previously reported that N-Mannich-based quinolon
      4(1H)-imines are potent antiplasmodial agents but present several stability
      liabilities. We now report our efforts to optimize quinolon-4(1H)-imines as dual
      stage antiplasmodial agents endowed with chemical and metabolic stability. We
      report compounds active against both the erythrocytic and exoerythrocytic forms
      of malaria parasites, such as the quinolon-4(1H)-imine 5p (IC50 values of 54 and
      710 nM against the erythrocytic and exoerythrocytic forms), which constitute
      excellent starting points for further lead optimization as dual-stage
      antimalarials. 

PMID- 24020773
TI  - Women's emotions one week after receiving or being denied an abortion in the
      United States.
AB  - CONTEXT: The notion that abortion causes poor mental health has gained traction,
      even though it is not supported by research. Few studies have comprehensively
      investigated women's postabortion emotions. METHODS: Baseline data from a
      longitudinal study of women seeking abortion at 30 U.S. facilities between 2008
      and 2010 were used to examine emotions among 843 women who received an abortion
      just prior to the facility's gestational age limit, were denied an abortion
      because they presented just beyond the gestational limit or obtained a first
      trimester abortion. Multivariable analyses were used to compare women's emotions
      about their pregnancy and about their receipt or denial of abortion after one
      week, and to identify variables associated with experiencing primarily negative
      emotions postabortion. RESULTS: Compared with women who obtained a near-limit
      abortion, those denied the abortion felt more regret and anger (scoring, on
      average, 0.4-0.5 points higher on a 0-4 scale), and less relief and happiness
      (scoring 1.4 and 0.3 points lower, respectively). Among women who had obtained
      the abortion, the greater the extent to which they had planned the pregnancy or
      had difficulty deciding to seek abortion, the more likely they were to feel
      primarily negative emotions (odds ratios, 1.2 and 2.5, respectively). Most (95%)
      women who had obtained the abortion felt it was the right decision, as did 89% of
      those who expressed regret. CONCLUSIONS: Difficulty with the abortion decision
      and the degree to which the pregnancy had been planned were most important for
      women's postabortion emotional state. Experiencing negative emotions postabortion
      is different from believing that abortion was not the right decision.

PMID- 24020774
TI  - Sexual health resources at Minnesota colleges: associations with students' sexual
      health behaviors.
AB  - CONTEXT: Sexual risk behaviors are common among college students, and research
      examining the environmental context of these behaviors is important for
      prevention. The presence of college sexual health resources is a potentially
      important part of that context. METHODS: In a 2010-2011 survey, 6,318
      undergraduates from 28 two- and four-year Minnesota college campuses provided
      data on their sexual health behaviors. In addition, a specially designed
      inventory was used to assess the sexual health resources available on each
      campus. Multilevel regression was used to test the associations of four types of
      resources with students' condom use, birth control use, STD or HIV testing, and
      unplanned pregnancy. RESULTS: In models that controlled for students' personal
      and demographic characteristics, the higher the level of sexual health resources
      at a college, the lower the likelihood that students had had intercourse without
      birth control, intercourse without a condom and involvement in unplanned
      pregnancy. For example, students attending colleges with the maximum number of
      general clinic resources had a lower predicted probability of reporting nonuse of
      reliable birth control at last intercourse than students attending colleges with
      no resources (7% vs. 14%). After college characteristics were adjusted for, most
      measures of resources remained significant, although associations were reduced;
      two measures became significant in unexpected directions. CONCLUSIONS: Colleges'
      provision of sexual health resources may be associated with students' sexual
      health behaviors. Research using quasi-experimental or experimental designs is
      needed to assess the mechanisms underlying these associations; such work could
      lead to interventions that might help reduce students' risky behaviors.

PMID- 24020775
TI  - Racial and ethnic differences in U.S. women's choice of reversible
      contraceptives, 1995-2010.
AB  - CONTEXT: In the United States, unintended pregnancies disproportionately affect
      minority populations. Persistent disparities in contraceptive use between black
      and Hispanic women and white women have been identified, but it is unclear
      whether racial and ethnic differences in use of the most effective methods have
      changed. METHODS: Data on 4,727 women from the 1995 National Survey of Family
      Growth and 5,775 women from the 2006-2010 cycle were used to examine the
      association between race and ethnicity and women's choice of reversible
      contraceptives according to level of method effectiveness. Stepwise multinomial
      logistic regressions were used to identify changes in this association between
      cycles. Analyses controlled for demographic, socioeconomic, family, religious,
      behavioral and geographic characteristics. RESULTS: The proportion of women using
      the most effective reversible contraceptive methods increased from 46% in 1995 to
      53% in 2006-2010. In 1995, black and Hispanic women's use of the most effective
      reversible contraceptives did not differ from that of white women. By 2006-2010,
      however, black women were substantially less likely than white women to use
      highly effective reversible contraceptive methods rather than no method (relative
      risk ratio, 0.6). An analysis that combined the two data sets and included a term
      for the interaction between survey year and race and ethnicity found that
      relative to white women, black women were less likely in 2006-2010 than in 1995
      to use more effective methods rather than no method (0.6). CONCLUSIONS: Further
      research is needed to identify factors that may be causing racial and ethnic
      disparities in contraceptive decisions to widen.

PMID- 24020776
TI  - Relationship characteristics and feelings about pregnancy among black and puerto
      rican young adults.
AB  - CONTEXT: Unintended pregnancy is common among black and Hispanic young adults in
      the United States. How pregnancy intentions form and change is poorly understood,
      although research indicates that intentions and attitudes are dependent on
      partners' views and other relationship factors, and are different by gender.
      METHODS: A sample of black and Puerto Rican men and women aged 18-25 from low
      income neighborhoods in two cities were surveyed in 2007-2008. Using data on 520
      serious and casual sexual relationships reported by 460 respondents, generalized
      ordered logistic regression analysis was conducted to identify individual- and
      relationship-level correlates of how respondents would feel if they became
      involved in a pregnancy with a particular partner. RESULTS: About one-quarter of
      respondents reported each of four possibilities of how they would feel about a
      pregnancy with a particular partner-very upset, a little upset, a little pleased
      and very pleased. In 45% of relationships, respondents believed that their
      partners would be very pleased about a pregnancy, whereas they themselves would
      be very pleased in only one-quarter of cases. Overall, women were less likely to
      feel positive about a pregnancy than were men (odds ratio, 0.3). Respondents'
      positive feelings about their relationships were associated with a strong
      tendency toward more positive feelings about a pregnancy (2.1), as was a measure
      of how positive respondents thought their partners would feel (1.5-2.6). The
      latter association was particularly strong among women (1.7). CONCLUSIONS:
      Relationship characteristics were associated with feelings about pregnancy for
      both genders. Future research should utilize a more comprehensive framework for
      conceptualizing and examining sexual relationships.

PMID- 24020777
TI  - Hysterectomy and disability among U.S. women.
AB  - CONTEXT: Hysterectomies are the second most common surgery performed on women in
      the United States, and most are done for elective reasons. Although women with
      disabilities appear to have an increased risk of undergoing the procedure, little
      research has evaluated the relationship between disability and hysterectomy.
      METHODS: Data on 42,842 women aged 18 or older from the 2000, 2005 and 2010
      National Health Interview Surveys were used to evaluate the relationship between
      disability and the risk of having a hysterectomy over the life course. Piecewise
      exponential event history models were estimated to identify associations between
      timing of disability onset, type of disability, and the occurrence and timing of
      hysterectomy. RESULTS: Women with multiple disabilities experienced a higher risk
      of undergoing a hysterectomy than women with no disability (hazard ratio, 1.3),
      and this heightened risk was concentrated at younger ages. During their 20s, 30s
      and early 40s, women who had multiple disabilities were more likely to have had a
      hysterectomy than were their same-age counterparts with no or one disability (1.3
      2.4). Women with a single type of disability, as well as most women who had
      multiple disabilities and were aged 46 or older, were not at increased risk of
      having had a hysterectomy. CONCLUSIONS: Additional research is needed to
      investigate why young women with multiple disabilities appear to face an
      increased risk of having a hysterectomy, especially because it is major surgery
      that can carry significant health risks.

PMID- 24020778
TI  - Insurance and access implications of an over-the-counter switch for a progestin
      only pill.

PMID- 24020786
TI  - In vivo monitoring of serotonin in the striatum of freely moving rats with one
      minute temporal resolution by online microdialysis-capillary high-performance
      liquid chromatography at elevated temperature and pressure.
AB  - Online monitoring of serotonin in striatal dialysate from freely moving rats was
      carried out for more than 16 h at 1 min time resolution using microdialysis
      coupled online to a capillary HPLC system operating at about 500 bar and 50 
      degrees C. Several aspects of the system were optimized toward robust, in vivo
      online measurements. A two-loop, eight-port rotary injection valve demonstrated
      better consistency of continuous injections than the more commonly used two-loop,
      10-port valve. A six-port loop injector for introducing stimulating solutions
      (stimulus injector) was placed in-line between the syringe pump and microdialysis
      probe. We minimized solute dispersion by using capillary tubing (75 MUm inside
      diameter, 70 cm long) for the probe inlet and outlet. In vitro assessment of
      concentration dispersion during transport with a 30 s time resolution showed that
      the dispersion standard deviation for serotonin was well within the desired
      system temporal resolution. Each 30 or 60 s measurement reflects the integral of
      the true time response over the measurement time. We have accounted for this
      mathematically in determining the concentration dispersion during transport. The
      delay time between a concentration change at the probe and its detection is 7
      min. The timing of injections from the stimulus injector and the cycle time for
      the HPLC monitoring of the flow stream were controlled. The electrochemical
      detector contained a 13 MUm spacer to minimize detector dead volume. During in
      vivo experiments, retention time and separation efficiency were stable and
      reproducible. There was no statistically significant change over 5.5 h in the
      electrochemical detector sensitivity factor for serotonin. Dialysate serotonin
      concentrations change significantly in response to a 120 mM K(+) stimulus.
      Release of serotonin evoked by a 10 min, 120 mM K(+) stimulation, but not for
      other K(+) stimuli, exhibited a reproducible, oscillating profile of dialysate
      serotonin concentration versus time. Infusion of fluoxetine, a serotonin uptake
      inhibitor, increased dialysate serotonin concentrations and stimulated release
      magnitude. Transient serotonin increases were observed in response to the stress
      associated with unexpected handling. This system is simple, efficient, reliable,
      and suitable for the study of serotonin neurochemistry associated with emotion
      and behavior. 

PMID- 24020787
TI  - Saccharification of pumpkin residues by coculturing of Trichoderma reesei RUT-C30
      and Phanerochaete chrysosporium Burdsall with delayed inoculation timing.
AB  - Trichoderma reesei and Phanerochaete chrysosporium with different lignocellulose
      degrading enzyme systems have received much attention due to their ability to
      biodegrade lignocellulosic biomass. However, the synergistic effect of the two
      fungi on lignocellulose degradation is unknown. Herein, a cocultivation of T.
      reesei RUT-C30 and P. chrysosporium Burdsall for biodegradation of
      lignocellulosic pumpkin residues (PRS) was developed to produce soluble
      saccharide. Results indicated that a cocultivation of the two fungi with P.
      chrysosporium Burdsall inoculation delayed for 1.5 days produced the highest
      saccharide yield of 53.08% (w/w), and only 20.83% (w/w) of PRS were left after
      one batch of fermentation. In addition, this strategy increased the activities of
      secreted cellulases (endoglucanase, cellobiohydrolase, and beta-glucosidase) and
      ligninases (lignin peroxidase and manganese peroxidase), which correlated to the
      increased saccharide yield. Besides, the resulting monosaccharides including
      glucose (1.23 mg/mL), xylose (0.13 mg/mL), arabinose (0.46 mg/mL), and fructose
      (0.21 mg/mL) from cocultures exhibited much higher yields than those from
      monoculture, which provides basal information for further fermentation research.
      This bioconversion of PRS into soluble sugars by cocultured fungal species
      provides a low cost method based on lignocellulose for potential biofuels or
      other bioproduct production. 

PMID- 24020788
TI  - Haemorrhagic pneumonia in sled dogs caused by Streptococcus equi subsp.
      zooepidemicus - one fatality and two full recoveries: a case report.
AB  - In spite of yearly vaccination, outbreaks of canine infectious respiratory
      disease are periodically seen amongst domestic dogs. These infections compromise
      host defense mechanisms, and, when combined with other stressful events, allow
      opportunistic pathogens like Streptococcus equi subsp. zooepidemicus to create
      serious disease. Early recognition and treatment are tremendously important for a
      successful outcome in these cases. A polyvalent vaccine was given to 22 racing
      dogs three days after a competition, followed by two days of rest, and then the
      dogs were returned to regular training. Coughing was noticed among the dogs four
      days after immunisation. Three days after this outbreak one of the dogs was
      unusually silent and was found dead the next morning. Simultaneously two other
      dogs developed haemorrhagic expectorate, depression and dyspnea and were brought
      in to the veterinary hospital. Streptococcus equi subsp. zooepidemicus was
      isolated in pure culture from all three cases. They were treated and
      rehabilitated successfully, and won a sledge race three months later. This paper
      discusses the necropsy results, treatment regime, rehabilitation and the
      chronology of vaccination, stressful events and disease.

PMID- 24020789
TI  - A novel technique for osteotome internal sinus lifts with simultaneous placement
      of tapered implants to improve primary stability.

PMID- 24020791
TI  - Regularly irregular atrial tachycardia following an orthotopic heart transplant:
      what is the mechanism?

PMID- 24020790
TI  - Risk factors for overweight/obesity in preschool children: an ecological
      approach.
AB  - BACKGROUND: Identification of risk factors is critical to preventing the
      childhood obesity epidemic. Risk factors that contribute to obesity are
      multifactorial. However, limited research has focused on identifying obesity risk
      factors using an ecological approach. METHODS: Baseline self-report survey data
      from the STRONG Kids program were used. The sample consisted of 329 parent-child
      dyads recruited from childcare programs in east-central Illinois. Child height
      and weight were measured and converted to age- and sex-specific z-scores using
      standard growth charts. An ecological model provided the theoretical framework
      for the selection of 22 previously reported childhood obesity risk factors.
      Multiple logistic regression analyses were used to identify risk factors.
      RESULTS: Of 22 potential risk factors, three were found to be significantly
      associated with child overweight/obesity. These included child nighttime sleep
      duration (chi(2)=8.56; p=0.003), parent BMI (chi(2)=5.62; p=0.01), and parental
      restrictive feeding for weight control (chi(2)=4.77; p=0.02). Children who slept
      for 8 hours and less were 2.2 times more likely to be overweight/obese [95%
      confidence interval (CI): 1.3-3.7), whereas children with an overweight/obese
      parent were 1.9 times more likely to be overweight/obese (95% CI: 1.12-3.2).
      Finally, children whose parents used restrictive feeding practices were 1.75
      times more likely to be overweight/obese (95% CI: 1.06-2.9). CONCLUSIONS: Using
      an ecological approach, we conclude that childhood obesity prevention efforts may
      benefit from targeting the key risk factors of child sleep duration, parent BMI,
      and parental restrictive feeding practices as focus areas for obesity prevention.

PMID- 24020792
TI  - Experiences of parents whose sons or daughters have (had) attempted suicide.
AB  - AIM: The aim of this exploratory study was to gain further insights into the
      experiences of parents of sons or daughters who have attempted suicide and how
      these parents respond to the increased psychosocial burden following the suicide
      attempt(s). BACKGROUND: Suicide is a major public health problem and relatives
      are understood as playing an important role in suicide prevention; however,
      suicide and suicidal behaviour affect the relatives' lives profoundly, both
      emotionally and socially, and the psychosocial impact on families is
      underresearched. DESIGN: Focus groups with parents of sons or daughters who have
      attempted suicide. METHODS: In January and February 2012, we interviewed two
      groups of parents recruited at a counselling programme for relatives of persons
      who have attempted suicide. The analysis combined a thematic analysis with a
      subsequent analysis of how the themes were negotiated in the conversational
      interactions. The findings were interpreted and discussed within an
      interactionist framework. FINDINGS: The participants in the study described their
      experiences as a double trauma, which included the trauma of the suicide
      attempt(s) and the subsequent psychosocial impact on the family's well-being. The
      pressure on the parents was intense and the fundamentally unpredictable character
      of suicide attempts was frequently emphasized. CONCLUSION: Being the parent of a
      child who attempts suicide meant managing a life-threatening situation and the
      additional moral stigma. In part, the participants did this in the group by
      negotiating the character of the suicide attempt(s) and who was responsible.

PMID- 24020793
TI  - New method for evaluation of early phase tear clearance by anterior segment
      optical coherence tomography.
AB  - PURPOSE: To describe a new method of measuring early phase tear clearance by
      anterior segment optical coherence tomography (AS-OCT). METHODS: Sixty normal
      subjects were divided into a young group (30 subjects; 29.6 +/- 7.2 years) and an
      elder group (30 subjects; 71.4 +/- 10.8 years). AS-OCT (CASIA SS-1000, Tomey,
      Japan) with customized software was used to record the tear meniscus at the
      centre of the lower eyelid. Five microlitres of lukewarm saline solution was
      dropped into the lower conjunctival sac, and an image of the tear meniscus was
      obtained immediately and again 30 seconds after natural blinking. The tear
      meniscus height (TMH) and tear meniscus area (TMA) were measured in the AS-OCT
      images, and the percentage decrease in the TMH and TMA was used as a measure of
      the tear clearance. Correlations between tear clearance and clinical features
      including degree of conjunctivochalasis, degree of protrusion of inferior
      lacrimal punctum, distance of lacrimal punctum from the Marx line and fluorescein
      clearance rates were also determined in another healthy population consisting of
      30 subjects. RESULTS: The OCT tear clearance rate was 35.2 +/- 11% for TMH and
      28.1 +/- 12.4% for TMA in the young group, and 12.4 +/- 7.3% and 6.2 +/- 9.1%,
      respectively in the elder group. The differences were significant for both the
      TMH (p = 0.017) and the TMA (p = 0.024). The OCT-determined tear clearance was
      positively correlated with the fluorescein clearance rate, and negatively
      correlated with the distance between the lacrimal punctum and Marx line, degree
      of conjunctivochalasis and degree of lacrimal punctum protrusion. CONCLUSION: AS
      OCT can be used as a rapid, non-invasive and quantitative method of determining
      the early phase tear clearance rate in a normal healthy population.

PMID- 24020794
TI  - Sex differences in the prognostic significance of KRAS codons 12 and 13, and BRAF
      mutations in colorectal cancer: a cohort study.
AB  - BACKGROUND: Activating KRAS and BRAF mutations predict unresponsiveness to EGFR
      targeting therapies in colorectal cancer (CRC), but their prognostic value needs
      further validation. In this study, we investigated the impact of KRAS codons 12
      and 13, and BRAF mutations on survival from CRC, overall and stratified by sex,
      in a large prospective cohort study. METHODS: KRAS codons 12 and 13, and BRAF
      mutations were analysed by pyrosequencing of tumours from 525 and 524 incident
      CRC cases in The Malmo Diet and Cancer Study. Associations with cancer-specific
      survival (CSS) were explored by Cox proportional hazards regression, unadjusted
      and adjusted for age, TNM stage, differentiation grade, vascular invasion and
      microsatellite instability (MSI) status. RESULTS: KRAS and BRAF mutations were
      mutually exclusive. KRAS mutations were found in 191/ 525 (36.4%) cases, 82.2% of
      these mutations were in codon 12, 17.3% were in codon 13, and 0.5% cases had
      mutations in both codons. BRAF mutations were found in 78/524 (14.9%) cases.
      Overall, mutation in KRAS codon 13, but not codon 12, was associated with a
      significantly reduced CSS in unadjusted, but not in adjusted analysis, and BRAF
      mutation did not significantly affect survival. However, in microsatellite stable
      (MSS), but not in MSI tumours, an adverse prognostic impact of BRAF mutation was
      observed in unadjusted, but not in adjusted analysis. While KRAS mutation status
      was not significantly associated with sex, BRAF mutations were more common in
      women. BRAF mutation was not prognostic in women; but in men, BRAF mutation was
      associated with a significantly reduced CSS in overall adjusted analysis (HR =
      3.50; 95% CI = 1.41-8.70), but not in unadjusted analysis. In men with MSS
      tumours, BRAF mutation was an independent factor of poor prognosis (HR = 4.91;
      95% CI = 1.99-12.12). KRAS codon 13 mutation was associated with a significantly
      reduced CSS in women, but not in men in unadjusted, but not in adjusted analysis.
      CONCLUSIONS: Results from this cohort study demonstrate sex-related differences
      in the prognostic value of BRAF mutations in colorectal cancer, being
      particularly evident in men. These findings are novel and merit further
      validation.

PMID- 24020795
TI  - Polydactyly: phenotypes, genetics and classification.
AB  - Polydactyly is one of the most common hereditary limb malformations featuring
      additional digits in hands and/or feet. It constituted the highest proportion
      among the congenital limb defects in various epidemiological surveys.
      Polydactyly, primarily presenting as an additional pre-axial or post-axial digit
      of autopod, is a highly heterogeneous condition and depicts broad inter- and
      intra-familial clinical variability. There is a plethora of polydactyly
      classification methods reported in the medical literature which approach the
      heterogeneity in polydactyly in various ways. In this communication, well
      characterized, non-syndromic polydactylies in humans are reviewed. The cardinal
      features, phenotypic variability and molecular advances of each type have been
      presented. Polydactyly at cellular and developmental levels is mainly a failure
      in the control of digit number. Interestingly, GLI3 and SHH (ZRS/SHH enhancer),
      two antagonistic factors known to modulate digit number and identity during
      development, have also been implicated in polydactyly. Mutations in GLI3 and
      ZRS/SHH cause overlapping polydactyly phenotypes highlighting shared molecular
      cascades in the etiology of additional digits, and thus suggesting the lumping of
      at least six distinct polydactyly entities. However, owing to the extreme
      phenotypic and clinical heterogeneity witnessed in polydactyly a substantial
      genetic heterogeneity is expected across different populations and ethnic groups.

PMID- 24020796
TI  - VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis:
      protective effects of a VEGF164b therapy.
AB  - BACKGROUND: Ulcerative colitis (UC) is the most common form of inflammatory bowel
      disease in the USA. A key component of UC is the increase in inflammatory
      angiogenesis of the colon during active disease. This increase is driven to a
      great extent by the over expression of VEGF-A. Recently, VEGF165(b) (VEGF164(b)
      in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was
      determined to be disturbed in many pathologies such as cancer and pre-eclampsia.
      RESULTS: The aims of this study were to examine the role of this inhibitory VEGF
      by expressing this molecule in a model of intestinal inflammation, and to
      evaluate its expression as a potential new therapeutic approach for treating UC.
      A modified model of TNBS colitis was used to determine the effects of rVEGF164(b)
      expression on colon inflammation. Expansion of the vascular system was assessed
      by immunhistochemical methods and macro- and microscopic measurements of
      inflammation in the colon were measured. Leukocyte invasion of the tissue was
      measured by myeloperoxidase assay and identification and counting of lymphoid
      follicles. Both angio- and lymphangiogenesis were reduced by expression of
      rVEGF164(b), which correlated with reduction in both gross and microscopic
      inflammatory scores. Leukocyte invasion of the tissue was also reduced by
      rVEGF164(b) expression. CONCLUSIONS: This is the first report using an endogenous
      inhibitory VEGF-A isoform for therapy in a model of experimental colitis.
      Inhibitory VEGF molecules play an important role in maintenance of gut
      homeostasis and may be dysregulated in UC. The results of this study suggest that
      restoration of rVEGF164(b) expression has anti-inflammatory activity in a TNBS
      model and warrants further examination as a possible therapeutic for UC.

PMID- 24020798
TI  - In emergently ventilated trauma patients, low end-tidal CO2 and low cardiac
      output are associated and correlate with hemodynamic instability, hemorrhage,
      abnormal pupils, and death.
AB  - BACKGROUND: In a smaller experience, the authors previously demonstrated that end
      tidal carbon dioxide (PetCO2) and cardiac output (CO) had a positive association
      in emergently intubated trauma patients during Emergency Department
      resuscitation. The aim of this larger study was to reassess the relationship of
      PetCO2 with CO and identify patient risk-conditions influencing PetCO2 and CO
      values. METHODS: The investigation consists of acutely injured trauma patients
      requiring emergency tracheal intubation. The study focuses on the prospective
      collection of PetCO2 and noninvasive CO monitor (NICOM(r)) values in the
      Emergency Department. RESULTS: From the end of March through August 2011, 73
      patients had 318 pairs of PetCO2 (mm Hg) and CO (L/min.) values. Mean data
      included Injury Severity Score (ISS) >=15 in 65.2%, Glasgow Coma Score of 6.4 +/-
      4.6, hypotension in 19.0%, and death in 34.3%. With PetCO2 <= 25 (15.9 +/- 8.0),
      systolic blood pressure was 77.0 +/- 69, CO was 3.2 +/- 3.0, cardiac arrest was
      60.4%, and mortality was 84.9%. During hypotension, CO was lower with major blood
      loss (1.9), than without major loss (5.0; P = 0.0008). Low PetCO2 was associated
      with low CO (P < 0.0001). Low PetCO2 was associated (P <= 0.0012) with ISS > 20,
      hypotension, bradycardia, major blood loss, abnormal pupils, cardiac arrest, and
      death. Low CO was associated (P <= 0.0059) with ISS > 20, hypotension,
      bradycardia, major blood loss, abnormal pupils, cardiac arrest, and death.
      CONCLUSIONS: During emergency department resuscitation, a decline in PetCO2
      correlates with decreases in noninvasive CO in emergently intubated trauma
      patients. Decreasing PetCO2 and declining NICOM CO are associated with
      hemodynamic instability, hemorrhage, abnormal pupils, and death. The study
      indicates that NICOM CO values are clinically discriminate and have physiologic
      validity.

PMID- 24020799
TI  - Using a combined theoretical and experimental approach to understand the
      structure and dynamics of imidazolium-based ionic liquids/water mixtures. 2.
      EXAFS spectroscopy.
AB  - Extended X-ray absorption fine structure (EXAFS) spectroscopy is employed, in
      conjunction with molecular dynamics (MD) simulations, to investigate the
      interaction of water with the Br(-) ion in an imidazolium-based ionic liquid
      (IL). 1-Butyl-3-methylimidazolium bromide/water mixtures with molar ratios
      ranging from 1:3 to 1:200 have been analyzed, and a clear picture of the
      structural arrangements of the water molecules inside the IL has been obtained
      from the synergic interpretation of the EXAFS and MD data. At the lowest
      investigated water content, the presence of water is mainly detected around the
      Br(-) anion. Upon increasing the water fraction, more water molecules enter the
      Br(-) first-coordination shell but always in a lower number than what is needed
      to saturate the inner sphere. This suggests that interactions also exist between
      water and the imidazolium cation. The existence of tight ion pairs has been
      evidenced, even when water is present in the mixtures in great excess. 

PMID- 24020800
TI  - Endocannabinoid system as a potential mechanism for n-3 long-chain
      polyunsaturated fatty acid mediated cardiovascular protection.
AB  - The presence of an active and functioning endocannabinoid (EC) system within
      cardiovascular tissues implies that this system has either a physiological or
      pathophysiological role (or both), and there is a substantial literature to
      support the notion that, in the main, they are protective in the setting of
      various CVD states. Moreover, there is an equally extensive literature to
      demonstrate the cardio- and vasculo-protective effects of n-3 long-chain (LC)
      PUFA. It is now becoming evident that there appears to be a close relationship
      between dietary intervention with n-3 LC-PUFA and changes in tissue levels of EC,
      raising the question as to whether or not EC may, at least in part, play a role
      in mediating the cardio-and vasculo-protective effects of n-3 LC-PUFA. This brief
      review summarises the current understanding of how both EC and n-3 LC-PUFA exert
      their protective effects in three major cardiovascular disorders (hypertension,
      atherosclerosis and acute myocardial infarction) and attempts to identify the
      similarities and differences that may indicate common or integrated mechanisms.
      From the data available, it is unlikely that in hypertension EC mediate any
      beneficial effects of n-3 LC-PUFA, since they do not share common mechanisms of
      blood pressure reduction. However, inhibition of inflammation is an effect shared
      by EC and n-3 LC-PUFA in the setting of both atherosclerosis and myocardial
      reperfusion injury, while blockade of L-type Ca2+ channels is one of the possible
      common mechanisms for their antiarrhythmic effects. Although both EC and n-3 LC
      PUFA demonstrate vasculo- and cardio-protection, the literature overwhelmingly
      shows that n-3 LC-PUFA decrease tissue levels of EC through formation of EC-n-3
      LC-PUFA conjugates, which is counter-intuitive to an argument that EC may mediate
      the effects of n-3 LC-PUFA. However, the discovery that these conjugates have a
      greater affinity for cannabinoid receptors than the native EC provides a
      fascinating avenue for further research into novel approaches for the treatment
      and prevention of atherosclerosis and myocardial injury following
      ischaemia/reperfusion.

PMID- 24020801
TI  - Cellulosic carbon fibers with branching carbon nanotubes for enhanced
      electrochemical activities for bioprocessing applications.
AB  - Renewable biobased carbon fibers are promising materials for large-scale
      electrochemical applications including chemical processing, energy storage, and
      biofuel cells. Their performance is, however, often limited by low activity.
      Herein we report that branching carbon nanotubes can enhance the activity of
      carbonized cellulosic fibers, such that the oxidation potential of NAD(H) was
      reduced to 0.55 V from 0.9 V when applied for bioprocessing. Coordinating with
      enzyme catalysts, such hierarchical carbon materials effectively facilitated the
      biotransformation of glycerol, with the total turnover number of NAD(H) over 3500
      within 5 h of reaction. 

PMID- 24020802
TI  - Small bowel obstruction in patients with familial adenomatous polyposis related
      desmoid disease.
AB  - AIM: Intra-abdominal desmoid disease is one of the most common extra-intestinal
      manifestations of familial adenomatous polyposis. Small bowel obstruction occurs
      frequently in affected patients and is notoriously difficult to treat. The aim of
      this study was to review the management and outcome of desmoid-related small
      bowel obstruction. METHOD: This was a retrospective, descriptive study of
      patients with familial adenomatous polyposis and intra-abdominal desmoid disease
      who developed small bowel obstruction. Demographic data and data concerning the
      presentation, diagnosis and treatment of the bowel obstructions were abstracted
      from the polyposis database or patients' records. Patients with obstruction
      unrelated to desmoid disease were excluded. RESULTS: There were 47 patients (30
      women and 17 men). Median age at first bowel obstruction was 24.2 (interquartile
      range 19.2-34.2) years. The median time from index surgery to first bowel
      obstruction was 4.1 (interquartile range 1.5-9.0) years. Twenty-two patients had
      a colectomy and ileorectal anastomosis and 21 a proctocolectomy and ileoanal
      pouch. Obstruction was treated medically in 29% of cases and surgically in 69%.
      Thirteen patients had total parental nutrition. Thirty (63.8%) had a second
      episode of small bowel obstruction at a mean of 5.3 years after the first, 50% of
      which were treated medically. Eighteen (37.5%) patients had more than two
      episodes of bowel obstruction. There were 118 operations, including lysis of
      adhesions (29), small bowel resection (14), bypass (12), ileostomy (12), desmoid
      excision (9) and stricturoplasty (2). CONCLUSION: Desmoid-related small bowel
      obstruction in familial adenomatous polyposis patients requires multiple surgical
      strategies to restore a patent gastrointestinal tract. WHAT DOES THIS PAPER ADD
      TO THE LITERATURE?: This is the only series in the literature specifically
      addressing small bowel obstruction in patients with familial adenomatous
      polyposis and intra-abdominal desmoid disease. The data show that small bowel
      obstruction is common, tends to recur, but can be successfully managed by a
      combination of medical and well selected surgical treatment.

PMID- 24020803
TI  - New RHCE variant alleles encoding the D- - phenotype.
AB  - BACKGROUND: Variant alleles that do not produce RhCE antigens are rare.
      Consequently, they pose a challenge to transfusion when found in alloimmunized
      patients and make blood units valuable when found in donors. STUDY DESIGN AND
      METHODS: Five index cases and their relatives were studied by both serologic and
      molecular techniques. Genomic DNA was subjected to microarray genotyping,
      sequencing, exon scanning, and/or copy number determination assays to identify
      the RHCE allele(s) responsible for their D+ C- c- E- e- (D- -) phenotype.
      RESULTS: The five apparent D- - phenotypes were confirmed by molecular methods.
      Three of them contained unreported RHCE-null alleles, namely, RHCE*Ce-D(3-9)-Ce,
      RHCE*Ce87_93insT, and RHCE*cE221A. CONCLUSION: Molecular analysis of D- -
      phenotypes allows the identification of new RHCE-null variants. Conversely,
      detection of described RHCE-null variants facilitates confirmation of D- -
      phenotypes in patients and donors, helping improve transfusion safety.

PMID- 24020804
TI  - The context and practice of handwashing among new mothers in Serang, Indonesia: a
      formative research study.
AB  - BACKGROUND: This article reports on formative research into the context and
      practice of handwashing with soap by new mothers, which can substantially impact
      child morbidity and mortality. New mothers are an important target group for
      handwashing interventions: they are considered particularly susceptible to
      behaviour change and their actions can directly affect a child's health. METHODS:
      Twenty-seven mothers of infants (including neonates) from urban and rural sub
      districts of Serang were recruited and filmed over a period of eight hours. Video
      footage was used to identify handwashing occasions and to understand the context
      in which behaviour took place. Each woman was subsequently interviewed. RESULTS:
      Handwashing with soap was found to be infrequent, typically occurring after
      eating, cooking and household chores or after cleaning a child's bottom.
      Handwashing before preparing food or eating was rare. Pre-pregnancy routines were
      reported to have been disrupted. Advice on child care comes from many sources,
      particularly the midwife and new child's grandmother. CONCLUSIONS: Developing
      interventions to change perceptions and practice of handwashing would seed an
      important behaviour and could save lives. New mothers represent an ideal target
      group for such an intervention. We suggest that interventions target an increase
      in handwashing with soap after contact with own and a baby's faecal matter as
      part of the post-defecation hygiene routines. As the child's grandmother is an
      authoritative source of information about parenting, interventions focussed on
      improving newborn care could target grandmothers as well as midwives.

PMID- 24020805
TI  - Effects of carrying a backpack in a symmetrical manner on the shape of the feet.
AB  - The aim of this study was to assess changes in the shape of the feet while
      carrying a backpack constituting 10% of a child's weight. It was an
      observational, cross-sectional study involving 118 primary school children aged
      11-13 years. Selected parameters of foot shape were assessed in both a normal
      position and with a backpack using podoscopy and a CQ-ST examination device. The
      study revealed significant differences in the length and width of the right and
      left feet between assessments. Moreover, the longitudinal arch of the foot was
      significantly lowered and deformity of the great toe was reported. Carrying a
      backpack constituting 10% of a child's weight results in lowering of the
      longitudinal and traverse arches of the feet and advanced toe deformities.
      PRACTITIONER SUMMARY: We performed an observational, cross-sectional study
      examining the effect of carrying a backpack constituting 10% of a child's weight
      on parameters of foot shape and observed significant lowering of the longitudinal
      and traverse arches of the feet and advanced toe deformities.

PMID- 24020806
TI  - Eunicellin-based diterpenoids from the Formosan soft coral Klyxum molle with
      inhibitory activity on superoxide generation and elastase release by neutrophils.
AB  - Eleven new eunicellin-based diterpenoids possessing a cladiellane skeleton with a
      C-2, C-9 ether bridge, klymollins I-S (1-11), have been isolated from the EtOAc
      extract of the soft coral Klyxum molle from Taiwan waters. The structures of
      compounds 1-11 were elucidated by extensive spectroscopic analysis, including 2D
      NMR spectroscopy (COSY, HSQC, HMBC, and NOESY). Compound 5 exhibited cytotoxicity
      toward several cancer cell lines. Compound 5 is the first eunicellin-based
      metabolite bearing a phenyl group and displays significant inhibition of both
      superoxide anion generation and elastase release in N-formyl-methionyl-leucyl
      phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils. 

PMID- 24020807
TI  - Defects in mitochondrial distribution during the prolonged lag phase of
      Saccharomyces cerevisiae preceding growth in glycerol as the sole source of
      carbon.
AB  - The Saccharomyces cerevisiae strain CBS6412 has been shown to be able to grow in
      synthetic medium containing glycerol as the sole carbon source, conditions under
      which laboratory strains such as CEN.PK and S288c cannot grow. Nonetheless, this
      strain exhibits a lag phase of c. 30-40 h following transition to glycerol
      medium. As mitochondria play a critical role in the dissimilation of the
      respiratory carbon source glycerol, we investigated mitochondrial function and
      dynamics throughout the lag phase using mitochondria-targeted roGFP, a redox
      sensitive GFP variant. We found that following transition to glycerol medium,
      mitochondria become more oxidizing, accumulate near the bud neck, and exhibit
      decreased inheritance into daughter cells. Directly preceding entry into
      exponential growth phase, mitochondria become more reducing, mitochondrial
      accumulations at the bud neck decrease, and inheritance of mitochondria into
      daughter cells is restored. 

PMID- 24020808
TI  - Plasma membrane density of GABA(B)-R1a, GABA(B)-R1b, GABA-R2 and trimeric G
      proteins in the course of postnatal development of rat brain cortex.
AB  - With the aim to understand the onset of expression and developmental profile of
      plasma membrane (PM) content /density of crucial components of GABA(B)-R
      signaling cascade, GABA(B)-R1a, GABA(B)-R1b, GABA(B)-R2, G(i)1/G(i)2alpha,
      G(i)3alpha, G(o)alpha, G(z)alpha and Gbeta subunit proteins were determined by
      quantitative immunoblotting and compared in PM isolated from brain cortex of rats
      of different ages: between postnatal-day-1 (PD1) and 90 (PD90). PM density of
      GABA(B)-R1a, GABA(B)-R2, G(i)1/G(i)2alpha, G(i)3alpha, G(o)alpha, G(z)alpha and
      Gbeta was high already at birth and further development was reflected in parallel
      decrease of both GABA(B)-R1a and GABA(B)-R2 subunits. The major decrease of
      GABA(B)-R1a and GABA(B)-R2 occurred between the birth and PD15: to 55 % (R1a, **)
      and 51 % (R2, **), respectively. Contrarily, PM level of the cognate G-proteins
      G(i)1/G(i)2alpha, G(i)3alpha, G(o)alpha, G(z)alpha and Gbeta was unchanged in the
      course of the whole postnatal period of brain cortex development. Maturation of
      GABA(B)-R cascade was substantially different from ontogenetic profile of
      prototypical plasma membrane marker, Na, K-ATPase, which was low at birth and
      further development was reflected in continuous increase of PM density of this
      enzyme. Major change occurred between the birth and PD25. In adult rats, membrane
      content of Na, K-ATPase was 3-times higher than around the birth. 

PMID- 24020809
TI  - Morphology and contractility of cardiac myocytes in early stages of
      streptozotocin-induced diabetes mellitus in rats.
AB  - Diabetic cardiomyopathy is the leading cause of mortality in type 1 diabetes.
      Thus study of cardiomyocyte morphology and function during early stages of
      diabetes using modern analytical methods is of critical importance. Therefore,
      using confocal microscopy, we determined metric parameters, volumes and
      contractility, with calcium transients in isolated left-ventricular myocytes at
      one week after induction of diabetes in rats. Myocyte volume analysis from 3D
      confocal scans was performed using an automated contour detection algorithm that
      took the actual shape of the myocytes into account. We showed a significant
      reduction in myocyte volume in diabetic animals. We also showed a significant
      reduction in length and width but not in thickness of the myocytes, which
      suggests disproportional reorganization of the structure of the heart tissue
      during short-term diabetes. From a functional point of view, we observed a
      significant decrease in cell shortening at a stimulation frequency of 0.5 Hz.
      This was accompanied by a decrease in calcium transient amplitude. Together,
      these data suggest that impaired calcium handling is one of the factors that
      contributes to the observed decrease in myocyte shortening during early stages of
      streptozotocin-induced diabetes in rats. 

PMID- 24020810
TI  - Effect of block of alpha-1-adrenoceptors on overall motor activity but not on
      spatial cognition in the object-position recognition task.
AB  - Prazosin, an alpha(1)-adrenoceptor antagonist, is well known for its depressant
      effect on motivation and motor activity, while it has no effect on retention of
      spatial behavior in several tasks, e.g. in the Morris water maze and radial arm
      maze. The role of alpha(1)-adrenoceptors in operant tasks with stimulus
      controlled behavior has not yet been tested. The present study investigated the
      effect of prazosin on the modulation of overall motor activity and on cognitive
      performance in a spatial operant task called object-position recognition task,
      where operant behavior (lever pressing) was controlled by spatial stimuli
      displayed on a computer screen. This task has been previously showed to be
      hippocampal-dependent. Pre-test injection of prazosin at the dose of 3 mg/kg
      decreased the responding rate, while it did not affect the recognition of
      object's position. In conclusion, we validated the new cognitive test with a drug
      with known pharmacological effects on behavior and confirmed the depressant
      effect of prazosin on motor activity and no effect on retrieval of spatial memory
      in the hippocampal-dependent operant task. 

PMID- 24020811
TI  - Does obstructive sleep apnea worsen during REM sleep?
AB  - Although it is thought that obstructive sleep apnea (OSA) is worse during rapid
      eye movement (REM) sleep than in non-REM (NREM) sleep there are some
      uncertainties, especially about apnoe-hypopnoe-index (AHI). Several studies found
      no significant difference in AHI between both sleep stages. However, REM sleep is
      associated more with side sleeping compared to NREM sleep, which suggests that
      body position is a possible confounding factor. The main purpose of this study
      was to compare the AHI in REM and NREM sleep in both supine and lateral body
      position. A retrospective study was performed on 422 consecutive patients who
      underwent an overnight polysomnography. Women had higher AHI in REM sleep than
      NREM sleep in both supine (46.05+/-26.26 vs. 23.91+/-30.96, P<0.01) and lateral
      (18.16+/-27.68 vs. 11.30+/-21.09, P<0.01) body position. Men had higher AHI in
      REM sleep than NREM sleep in lateral body position (28.94+/-28.44 vs. 23.58+/
      27.31, P<0.01), however, they did not reach statistical significance in supine
      position (49.12+/-32.03 in REM sleep vs. 45.78+/-34.02 in NREM sleep, P=0.50). In
      conclusion, our data suggest that REM sleep is a contributing factor for OSA in
      women as well as in men, at least in lateral position. 

PMID- 24020812
TI  - Gastrodin ameliorates anxiety-like behaviors and inhibits IL-1beta level and p38
      MAPK phosphorylation of hippocampus in the rat model of posttraumatic stress
      disorder.
AB  - Gastrodin, a main constituent of a Chinese herbal medicine, has been shown to be
      effective in treating various mood disorders. The purpose of the present study
      was to determine whether gastrodin could ameliorate stress-associated behavior in
      a rat model of enhanced single prolonged stress (ESPS)-induced posttraumatic
      stress disorder (PTSD). Following ESPS, rats were administered orally with
      gastrodin (50, 100, or 200 mg/kg daily) or vehicle for 2 weeks. Animals were then
      tested in the open field and elevated plus-maze, and the levels of IL-6 and IL
      1beta, the expression of iNOS, p38 and phospho-p38 (p-p38) in hippocampus were
      also tested. ESPS exposure resulted in pronounced anxiety-like behavior, elevated
      IL-6 and IL-1beta levels, and the higher expression of iNOS and p-p38 in
      hippocampus. However, repeated treatment with gastrodin, particularly at higher
      doses, reversed the aforementioned changes, including anxiety-like behavior,
      levels of IL-6 and IL-1beta, and the expression of iNOS and the p38 MAPK
      phosphorylation. These results indicate that gastrodin possesses anxiolytic
      effect and may be an effective herbal preparation for the treatment of PTSD. 

PMID- 24020813
TI  - Intraventricular pressure gradients in heart failure.
AB  - The aim of the present study was to characterize intraventricular pressure
      gradients (IVPGs) in an animal model of chronic heart failure. New Zealand
      rabbits were treated with doxorubicin (heart failure group, n=5) or saline
      (control group, n=5) and instrumented with pressure catheters placed in the apex
      and outflow-tract of left ventricle (LV) and with sonomicrometer crystals placed
      in the apex and base of the LV free wall. In heart failure animals, ventricular
      filling was delayed and slower when compared with control animals. Moreover, the
      physiological nonuniformity observed between apical and basal segments in normal
      hearts was abolished in failing hearts. Simultaneously, physiological IVPGs
      observed during normal ventricular filling were entirely lost in heart failure
      animals. During ventricular emptying physiological nonuniformity between apical
      and basal segments observed in control animals was also abolished in heart
      failure animals. In failing hearts minimal length occurred later and almost at
      same time both in apical and in basal myocardial segments. Simultaneously, the
      characteristic IVPG pattern observed in healthy hearts during systole, which
      promotes ventricular emptying, was not observed in failing hearts. The present
      study showed that diastolic IVPGs, a marker of normal ventricular filling, and
      systolic IVPGs, a marker of normal ventricular emptying, are abolished in heart
      failure. 

PMID- 24020814
TI  - Age and heat exposure-dependent changes in antioxidant enzymes activities in
      rat's liver and brain mitochondria: role of alpha-tocopherol.
AB  - To investigate the role of mitochondrial antioxidant capacity during increased
      susceptibility to heat accompanied by the aging, young and aged Wistar rats were
      exposed on heat for 60 min. After heat exposure, hepatic and brain mitochondria
      were isolated. Our results revealed changes in antioxidant enzyme activities in
      liver and brain mitochondria from young and to a greater extent in aged rats. Our
      measurements of MnSOD, GPx and GR activity indicate greater reactive oxygen
      species production from the mitochondria of aged heat exposed in comparison to
      young heat exposed rats. Also in the aged rats, the effect of alpha-tocopherol
      treatment in the prevention of oxidative stress occurred as a result of heat
      exposure, is less pronounced. Taken together, our data suggest that mitochondria
      in aged rats are more vulnerable and less able to prevent oxidative changes that
      occur in response to acute heat exposure. 

PMID- 24020815
TI  - Antioxidant/oxidant status and cardiac function in bradykinin B(1)- and B(2)
      receptor null mice.
AB  - Kinin-vasoactive peptides activate two G-protein-coupled receptors (R), B(1)R
      (inducible) and B(2)R (constitutive). Their complex role in cardiovascular
      diseases could be related to differential actions on oxidative stress. This study
      investigated impacts of B(1)R or B(2)R gene deletion in mice on the cardiac
      function and plasma antioxidant and oxidant status. Echocardiography-Doppler was
      performed in B(1)R (B(1)R(-/-)) and B(2)R (B(2)R(-/-)) deficient and wild type
      (WT) adult male mice. No functional alteration was observed in B(2)R(-/-) hearts.
      B(1)R(-/-) mice had significantly lowered fractional shortening and increased
      isovolumetric contraction time. The diastolic E and A waves velocity ratio was
      similar in all mice groups. Thus B(1)R(-/-) mice provide a model of moderate
      systolic dysfunction, whereas B(2)R(-/-) mice displayed a normal cardiac
      phenotype. Plasma antioxidant capacity (ORAC) was significantly decreased in both
      B(1)R(-/-) and B(2)R(-/-) mice whereas the vitamin C levels were decreased in
      B(2)R(-/-) mice only. Plasma ascorbyl free radical was significantly higher in
      B(1)R(-/-) compared to WT and B(2)R(-/-) mice. Therefore, the oxidative stress
      index, ascorbyl free radical to vitamin C ratio, was increased in both B(1)R(-/-)
      and B(2)R(-/-) mice. Hence, B(1)R and B(2)R deficiency are associated with
      increased oxidative stress, but there is a differential imbalance between free
      radical production and antioxidant defense. The interrelationship between the
      differential B(1)R and B(2)R roles in oxidative stress and cardiovascular
      diseases remain to be investigated. 

PMID- 24020816
TI  - The impact of four different classes of anesthetics on the mechanisms of blood
      pressure regulation in normotensive and spontaneously hypertensive rats.
AB  - Most anesthetics induce characteristic hemodynamic changes leading to blood
      pressure (BP) reduction but the role of renin-angiotensin system (RAS),
      sympathetic nervous system (SNS) and nitric oxide (NO) synthesis in this BP
      reduction is unknown. We therefore studied the influence of four widely used
      anesthetics - pentobarbital (P), isoflurane (ISO), ketamine-xylazine (KX) and
      chloralose-urethane (CU) - on the participation of these vasoactive systems in BP
      maintenance. BP effects elicited by the acute sequential blockade of RAS
      (captopril), SNS (pentolinium) and NO synthase (L-NAME) were compared in
      conscious and anesthetized Wistar or spontaneously hypertensive rats (SHR).
      Except for pentobarbital all studied anesthetics evidenced by diminished BP
      responses to pentolinium. The absolute pentolinium-induced BP changes were always
      greater in SHR than Wistar rats. KX anesthesia eliminated BP response to
      pentolinium and considerably enhanced BP response to NO synthase inhibition in
      SHR. In both rat strains the anesthesia with ISO or CU augmented BP response to
      captopril, decreased BP response to pentolinium and attenuated BP response to NO
      synthase inhibition. In conclusion, pentobarbital anesthesia had a modest
      influence on BP level and its maintenance by the above vasoactive systems.
      Isoflurane and chloralose-urethane anesthesia may be used in cardiovascular
      experiments if substantial BP decrease due to altered contribution of RAS, SNS
      and NO to BP regulation does not interfere with the respective research aim.
      Major BP reduction (namely in SHR) due to a complete SNS absence is a major
      drawback of ketamine-xylazine anesthesia. 

PMID- 24020817
TI  - Treatment of rats with hypolipidemic compound pirinixic acid protects their
      hearts against ischemic injury: are mitochondrial K(ATP) channels and reactive
      oxygen species involved?
AB  - Hypolipidemic compound pirinixic acid (WY-14643, WY) is known to exert
      pleiotropic (other than primary) effects, such as activation of peroxisome
      proliferator-activated receptors (PPAR-alpha), transcription factors regulating
      different cardiac functions. Their role in ischemia-reperfusion (I/R) injury and
      cardioprotection is less clear, although protective effects of PPAR agonists have
      been documented. This study was designed to explore the effects of WY on the I/R
      injury in the rat heart and potential mechanisms involved, including
      mitochondrial K(ATP) channels (mitoK(ATP)) opening and production of reactive
      oxygen species (ROS). Langendorff-perfused hearts of rats intragastrally treated
      with WY (3 mg/kg/day) for 5 days and of control animals were subjected to 30-min
      global ischemia and 2-h reperfusion with or without 15-min perfusion with
      mitoK(ATP) blocker 5-hydroxydecanoate (5-HD) prior to I/R. Evaluation of the
      infarct size (IS, TTC staining) served as the main end-point of protection. Lipid
      peroxidation (a marker of ROS production) was determined by measurement of
      myocardial concentration of conjugated dienes (CD), whereas protein expression of
      endothelial NO synthase was analysed by Western blotting. A 2-fold increase in
      the cardiac protein levels of eNOS after treatment with WY was accompanied by
      lower post-I/R levels of CD compared with those in the hearts of untreated
      controls, although WY itself enhanced ROS generation prior to ischemia. IS was
      reduced by 47 % in the hearts of WY-treated rats (P<0.05), and this effect was
      reversed by 5-HD. Results suggest that PPAR-alpha activation may confer
      protection against lethal I/R injury in the rat heart that involves up-regulation
      of eNOS, mitoK(ATP) opening and reduced oxidative stress during I/R. 

PMID- 24020818
TI  - The unwounded skin remodeling in animal models of diabetes types 1 and 2.
AB  - Diabetes mellitus types 1 and 2 are chronic diseases that cause serious health
      complications, including dermatologic problems. The diabetic skin is
      characterized by disturbances in collagen metabolism. A tissue remodeling depends
      on the degradation of extracellular matrix through the matrix metalloproteinases,
      which are regulated by e.g. the tissue inhibitors of metalloproteinases. The
      balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix
      metalloproteinases (TIMPs) is essential to maintain homeostasis in the skin. The
      aim of this study was to determine the concentration of metalloproteinase 2,
      tissue inhibitor of metalloproteinase 3 and the concentration of collagen type 1
      in unwounded skin of diabetes type 1 and 2 and healthy controls. The treatment of
      diabetes resulted in a significant decrease of MMP2, increase of TIMP3 and COL1
      concentrations in the skin as compared to the untreated diabetic skin. The
      concentrations of MMP2 in the skin of treated rats did not show significant
      differences from the healthy control group. TIMP3 concentrations in the skin of
      treated rats are not returned to the level observed in the control group.
      Disturbances of the extracellular matrix of the skin are similar in diabetes type
      1 and 2. Application of insulin in diabetes therapy more preferably affects the
      extracellular matrix homeostasis of the skin. 

PMID- 24020819
TI  - Expression of lipolytic genes in adipose tissue is differentially regulated
      during multiple phases of dietary intervention in obese women.
AB  - The aim of this study was to investigate the time-course of the expression of key
      lipolysis-regulating genes in the subcutaneous adipose tissue (SCAT) during
      different phases of a 6-month dietary intervention. Fifteen obese women (BMI
      34.7+/-1.0 kg.m(-2)) underwent a 6-month dietary intervention consisting of 1
      month very low calorie diet (VLCD), followed by 2 months low calorie diet (LCD)
      and 3 months weight maintenance diet (WM). At each phase of the dietary
      intervention, a needle microbiopsy of the abdominal SCAT was obtained to evaluate
      mRNA expression of key lipolysis-regulating genes and a hyperinsulinemic
      euglycemic clamp (HEC) was performed. Dietary intervention induced a body weight
      reduction of 9.8 % and an improvement of insulin sensitivity as assessed by a
      HEC. Compared to pre-diet levels, mRNA levels of the adrenergic beta(2)-receptor
      in SCAT were higher at the end of VLCD and not different at the end of LCD and
      WM. In contrast, the expression of the adrenergic alpha(2)-receptor was lower at
      the end of VLCD and LCD compared to the pre-diet levels and did not differ at WM.
      Adipose triglyceride lipase and hormone-sensitive lipase levels were lower than
      the pre-diet levels at the end of LCD only, while phosphodiesterase-3B and the
      insulin receptor levels did not change throughout the dietary intervention. The
      results suggest that the regulation pattern of the genes that are involved in the
      control of lipolysis is different at the respective phases of the dietary
      intervention and depends on the duration of the diet and the status of energy
      balance. 

PMID- 24020821
TI  - Electrochemical detection of single microbeads manipulated by optical tweezers in
      the vicinity of ultramicroelectrodes.
AB  - Latex micrometric beads are manipulated by optical tweezers in the vicinity of an
      ultramicroelectrode (UME). They are optically trapped in solution and approached
      the electrode surface. After the electrochemical measurement, they are optically
      removed from the surface. The residence time of the particle on the electrode is
      thus controlled by the optical tweezers. The detection is based on diffusional
      hindrance by the insulating objects which alters the fluxes of the redox
      Ru(NH3)6(3+) species toward the UME and thus its mass-transfer limited current.
      We have optically deposited successively 1, 2, and 3 beads of 3-MUm radius on the
      UME surface, and we have recorded the variations of the current depending on
      their landing locations that were optically controlled. Finally we decreased the
      current by partially blocking the electroactive surface with a six-bead assembly.
      The variation of the steady-state current and the approach curves allow for the
      indirect electrochemical localization of the bead in the vicinity of the UME, not
      only when the bead is in contact but also when it is levitated at distances lower
      than the UME radius. These experiments show that single particles or more complex
      structures may be manipulated in situ in a contactless mode near the UME surface.
      From comparison with simulations, the electrochemical detection affords an
      indirect localization of the object in the UME environment. The developed
      approach offers a potential application for interrogating the electrochemical
      activity of single cells and nanoparticles. 

PMID- 24020820
TI  - Highly expressed MT-ND3 positively associated with histological severity of
      hepatic steatosis.
AB  - Hepatic steatosis is the accumulation of an excess amount of triglycerides and
      other fats inside liver cells resulting from abnormal hepatic lipid metabolism.
      Mitochondrial structural and molecular defects are involved in the progression of
      hepatic steatosis pathogenesis. Hepatic methylation and transcriptional activity
      of the mitochondrial-encoded NADH dehydrogenase (MT-ND) play a critical role in
      the progression of non-alcoholic fatty liver disease (NAFLD). However, the
      expression of MT-ND3 in hepatic steatosis has not been extensively studied. In
      this study, liver specimens were collected from different patients, and were
      subjected to immunohistochemistry. Primary hepatocytes were treated with
      oxidative stress, hypoxia, and lipotoxicity to investigate the respective roles
      of these factors on MT-ND3 expression and cell apoptosis by western blotting and
      flow cytometry, respectively. We found that increased MT-ND3 expression in human
      hepatic steatosis was positively associated with histological severity of hepatic
      steatosis. Hypoxia, H2O2 , and saturated fatty acid treatment induced cell
      apoptosis mediated by mitochondria. These three factors all had effects on MT-ND3
      expression in cultured hepatocytes. Taken together, MT-ND3 may play important
      roles in hepatic steatosis progress. Hypoxia, oxidative stress, and lipotoxicity
      could all influence expression of MT-ND3 and thus may play a role in the
      progression of hepatic steatosis.

PMID- 24020823
TI  - Peripheral insertion of umbilical cord.
AB  - Numerous studies have addressed the significance of marginal and membranous
      umbilical cord (UC) insertion. Recent reports suggest that an eccentrically
      inserted UC may also be important. This case-control study assessed the potential
      relevance of peripheral insertion of UC (PIUC), defined as <3 cm from the nearest
      margin. Singleton placentas (n  =  1418) submitted to the pathology department
      over an 18-month period were analyzed. Each case of PIUC (n  =  119) was matched
      with a control placenta of the same gestational age. Placentas with marginal or
      membranous UC and multiple gestations were excluded. The overall prevalence of
      PIUC was 8.4%, but PIUC frequency was significantly increased in premature births
      at <28 weeks (21.4%, P < 0.001). There was no association with other adverse
      pregnancy outcomes. PIUC was associated with decreased placental weight Z-score (
      0.69 +/- 0.92 versus -0.22 +/- 1.3, P  =  0.0056), but not fetal weight Z-score,
      suggesting increased utilization of placental reserve. PIUC was also associated
      with relatively elongated placentas (length minus width: 2.6 +/- 3.2 versus 1.0
      +/- 3.1, P  =  0.006). PIUC tended to be more frequent in young primiparous
      mothers and was significantly less common in women with a history of prior
      curettage (66% vs 50%, P  =  0.013). These data, together with equivalent rates
      of prior cesarean section, multiparity, and advanced maternal age, support a
      primary developmental disorder as opposed to secondary placental migration due to
      underlying uterine abnormalities ("trophotropism"). Except for a borderline
      significant association with findings suggestive of maternal malperfusion (P  = 
      0.078), PIUC was not associated with other placental lesions.

PMID- 24020822
TI  - Nanoencapsulation enhances epigallocatechin-3-gallate stability and its
      antiatherogenic bioactivities in macrophages.
AB  - We have successfully synthesized (-)-epigallocatechin-3-gallate (EGCG)
      encapsulated nanostructured lipid carriers (NLCE) and chitosan-coated NLCE
      (CSNLCE) using natural lipids, surfactant, chitosan, and EGCG. Nanoencapsulation
      dramatically improved EGCG stability. CSNLCE significantly increased EGCG content
      in THP-1-derived macrophages compared with nonencapsulated EGCG. As compared to
      10 MUM nonencapsulated EGCG, both NLCE and CSNLCE at the same concentration
      significantly decreased macrophage cholesteryl ester content. NLCE and CSNLCE
      significantly decreased mRNA levels and protein secretion of monocyte
      chemoattractant protein-1 (MCP-1) levels in macrophages, respectively. These data
      suggest that nanoencapsulated EGCG may have a potential to inhibit
      atherosclerotic lesion development through decreasing macrophage cholesterol
      content and MCP-1 expression. 

PMID- 24020824
TI  - The effect of cigarette smoking during pregnancy on mode of delivery in
      uncomplicated term singleton pregnancies.
AB  - OBJECTIVE: To examine the influence of cigarette smoking during pregnancy on mode
      of delivery. METHODS: A retrospective analysis of 6105 uncomplicated term
      singleton pregnancies for mode of delivery was performed with respect to smoking
      status. RESULTS: Of all, 680 (84.0%) smokers and 4588 (86.7%) non-smokers had a
      spontaneous vaginal delivery, 65 (8.0%) smokers and 393 (7.4%) non-smokers had an
      instrumental delivery and 65 (8.0%) smokers and 314 (5.9%) non-smokers had a
      cesarean delivery (p = 0.051). Smoking during pregnancy increased the risk of any
      operative or instrumental intervention by OR 1.240, 95% CI 1.012-1.523. Non
      reassuring fetal heart rate pattern that warranted either cesarean or
      instrumental intervention was present in 99 (12.2%) out of 810 smokers and in 392
      out of 5295 (7.4%) non-smokers, p < 0.001). Smoking during pregnancy increased
      the risk of non-reassuring fetal heart rate pattern that warranted either
      cesarean or instrumental intervention by OR 1.650 (95% CI 1.341-2.022).
      CONCLUSION: Women with uncomplicated term singleton pregnancies who smoke during
      pregnancy are at an increased risk of fetal compromise during labor (as judged by
      non-reassuring fetal heart rate pattern), leading to increased rates of operative
      delivery (cesarean either instrumental).

PMID- 24020825
TI  - Pathways to psychiatric care in urban north China: a general hospital based
      study.
AB  - BACKGROUND: Pathway studies highlight the help-seeking behaviors of patients with
      physical and mental illnesses. A number of studies in this field have been
      completed in various parts of the world. The purpose of this study is to explore
      the characteristics of the help-seeking pathways of patients with mental illness
      from urban north China at Mental Health Professional (MHP). METHODS: The pathway
      diagrams, which accounted for more than five percent of patients, were documented
      for 441 subjects using the translated version of the World Health Organization
      (WHO) pathway encounter form. The patterns and durations of care-seeking were
      analyzed in different diagnostic groups. The chi2-test and the Mann-Whitney U
      test were employed, as needed. RESULTS: Respondents visited the MHP through a
      variety of pathways. Approximately three-quarters of the patients took an
      indirect pathway (74.8% vs 25.2%, chi2 = 108.8, p < 0.0001), and on average, each
      patient consulted 3.4 caregivers. The vast majority of patients first visited
      local tertiary general hospitals (56.4% vs 4.1%, chi2 = 138.3, p < 0.0001) or
      local secondary general hospitals (24.8% vs 4.1%, chi2 = 40.96, p < 0.0001).
      However, only 9.6% of patients were diagnosed with mental disorders for the
      patients who first visited non-psychiatric hospitals. Of the patients who first
      contacted with psychiatry hospital, 55.6% received a professional diagnosis and
      finally reached the MHP because of the poor treatment or high-cost medical care.
      CONCLUSIONS: The majority of patients seek other pathways than to go to MHP
      directly and this may be due to stigma, and/or lack of knowledge. The study gives
      emphasis on the importance of improving skills and knowledge that will facilitate
      the recognition of psychiatric disorders in the community health centers, the
      general hospitals system and by private practitioners. The pathway described by
      this study may be helpful while preparing mental health programs in the future.

PMID- 24020826
TI  - In vivo confocal microscopy of conjunctiva in preservative-free timolol 0.1% gel
      formulation therapy for glaucoma.
AB  - PURPOSE: To evaluate the effects at 1 year of preservative-free timolol gel and
      preserved timolol eye drops on conjunctiva and tear parameters. METHODS: Forty
      patients with primary open-angle glaucoma or ocular hypertension were randomized
      to the two treatment groups and compared with 20 healthy age-matched controls.
      Clinical tests (IOP, Schirmer I test, and lacrimal film break-up time BUT) and in
      vivo conjunctival confocal microscopy (IVCM) were performed in all patients at
      baseline and after 12 months. IVCM (HRT II Rostock Cornea Module; Heidelberg
      Engineering GmbH, Heidelberg, Germany) was performed after topical anaesthesia in
      the four cardinal locations and at the corresponding limbus to analyse
      conjunctiva cells. The main IVCM outcomes were goblet cell density and epithelial
      regularity. RESULTS: IVCM and clinical parameters were similar in the three
      groups at baseline. After 12 months, intra-epithelial goblet cell density was
      significantly lower in the preserved (48.25 +/- 7.70) than in the preservative
      free beta-blocker group (86.83 +/- 22.17, p < 0.001) and controls (88.9 +/-
      18.33, p < 0.001). The epithelial layer was significantly more regular in the
      preserved beta-blocker medication group than in the preservative-free beta
      blocker group (p < 0.001) and the control group (p < 0.001). A significant
      reduction in both Schirmer I and BUT was found in the group of preserved timolol
      (respectively, 11.3 +/- 2.97 and 8.12 +/- 0.99) compared with preservative-free
      timolol (16.8 +/- 1.83 and 11.27 +/- 1.27, p < 0.001) and controls (17.8 +/- 1.87
      and 12.10 +/- 1.28, p < 0.001). CONCLUSIONS: Based on our IVCM data, preservative
      free beta-blocker gel induces less changes at ocular surface than preserved beta
      blockers, a fact that should be considered to obtain less adverse effects and
      maximal adherence to treatment in a chronic condition such as glaucoma.

PMID- 24020827
TI  - Should we test all defibrillators at the time of implantation? An unanswered
      question. Reply to the letter of Hadid et al.

PMID- 24020828
TI  - Internet-based intervention programme for obese adolescents and their families
      (Next.Step): research protocol of a controlled trial.
AB  - AIM: This paper describes the design and rationale of a controlled trial that
      aims to determine the effectiveness of an intervention programme in which the
      internet is used. BACKGROUND: Adolescent obesity is a major health problem, there
      being urgency to find effective interventions that induce behavioural change. The
      inclusion of the internet in the intervention may improve adolescents' adherence
      to the weight management programme and lead to adoption of healthier lifestyles.
      DESIGN: A clinical trial with a control group (non-randomized). METHODS:
      Participants are adolescents with appointments at a paediatric obesity clinic
      (Portugal). Sample size was calculated according to the power analysis. The
      experimental group will follow the standard treatment protocol and receive free
      access to the e-therapeutic platform. The control group will follow the standard
      treatment protocol and join a waiting list. Intervention length will be 36 weeks
      (24 weeks of direct intervention with a follow-up for 12 weeks). This study was
      approved by the Ethical Committee for Health (Lisbon, Portugal) in January 2012
      and funded by the Foundation for Science and Technology (Portugal) in December
      2012. DISCUSSION: The results of this research will promote reflection on new
      approaches directed to treat adolescent obesity and on the promotion of healthy
      behaviours. We expect to gather empirical evidence of the intervention programme
      effectiveness. The expectations lie on the population health gains, empowerment
      in decision-making and adoption of healthier lifestyles.

PMID- 24020829
TI  - Intra-thoracic fat volume is associated with myocardial infarction in patients
      with metabolic syndrome.
AB  - BACKGROUND: Visceral adiposity is increased in those with Metabolic Syndrome
      (MetS) and atherosclerotic disease burden. In this study we evaluate for
      associations between intra-thoracic fat volume (ITFV) and myocardial infarction
      (MI) in patients with MetS. METHODS: Ninety-four patients with MetS, MI or both
      were identified from a cardiovascular CMR clinical registry. MetS was defined in
      accordance to published guidelines; where-as MI was defined as the presence of
      subendocardial-based injury on late gadolinium enhancement imaging in a coronary
      vascular distribution. A healthy control group was also obtained from the same
      registry. Patients were selected into the following groups: MetS+/MI- (N = 32),
      MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification
      was performed using signal threshold analysis of sequential sagittal CMR datasets
      (HASTE) and indexed to body mass index. RESULTS: The mean age of the population
      was 59.8 +/- 12.5 years. MetS+ patients (N=64) demonstrated a significantly
      higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective
      MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a
      progressive elevation in the indexed ITFV (22.3 +/- 10.6, 28.6 +/- 12.6, 30.6 +/-
      12.3, and 35.2 +/- 1.4 ml/kg/m(2), (p = 0.002)). Among MetS+ patients those with
      MI showed a significantly higher indexed ITFV compared to those without MI (p =
      0.02). CONCLUSIONS: ITFV is elevated in patients with MetS and incrementally
      elevated among those with evidence of prior ischemic myocardial injury.
      Accordingly, the quantification of ITFV may be a valuable marker of myocardial
      infarction risk among patients with MetS and warrants further investigation.

PMID- 24020830
TI  - PUFA-derived endocannabinoids: an overview.
AB  - Following on from the discovery of cannabinoid receptors, of their endogenous
      agonists (endocannabinoids) and of the biosynthetic and metabolic enzymes of the
      endocannabinoids, significant progress has been made towards the understanding of
      the role of the endocannabinoid system in both physiological and pathological
      conditions. Endocannabinoids are mainly n-6 long-chain PUFA (LCPUFA) derivatives
      that are synthesised by neuronal cells and inactivated via a two-step process
      that begins with their transport from the extracellular to the intracellular
      space and culminates in their intracellular degradation by hydrolysis or
      oxidation. Although the enzymes responsible for the biosynthesis and metabolism
      of endocannabinoids have been well characterised, the processes involved in their
      cellular uptake are still a subject of debate. Moreover, little is yet known
      about the roles of endocannabinoids derived from n-3 LCPUFA such as EPA and DHA.
      Here, I provide an overview of what is currently known about the mechanisms for
      the biosynthesis and inactivation of endocannabinoids, together with a brief
      analysis of the involvement of the endocannabinoids in both food intake and
      obesity. Owing to limited space, recent reviews will be often cited instead of
      original papers.

PMID- 24020831
TI  - Predictors of physical and mental health-related quality of life outcomes among
      myocardial infarction patients.
AB  - BACKGROUND: Health-related quality of life (HRQoL) is an important outcome for
      patients diagnosed with coronary heart disease. This report describes predictors
      of physical and mental HRQoL at six months post-hospitalisation for myocardial
      infarction. METHODS: Participants were myocardial infarction patients (n=430)
      admitted to two tertiary referral centres in Brisbane, Australia who completed a
      six month coronary heart disease secondary prevention trial (ProActive Heart).
      Outcome variables were HRQoL (Short Form-36) at six months, including a physical
      and mental summary score. Baseline predictors included demographics and clinical
      variables, health behaviours, and psychosocial variables. Stepwise forward
      multiple linear regression analyses were used to identify significant independent
      predictors of six month HRQoL. RESULTS: Physical HRQoL was lower in participants
      who: were older (p<0.001); were unemployed (p=0.03); had lower baseline physical
      and mental HRQoL scores (p<0.001); had lower confidence levels in meeting
      sufficient physical activity recommendations (p<0.001); had no intention to be
      physically active in the next six months (p<0.001); and were more sedentary
      (p=0.001). Mental HRQoL was lower in participants who: were younger (p=0.01); had
      lower baseline mental HRQoL (p<0.001); were more sedentary (p=0.01) were
      depressed (p<0.001); and had lower social support (p=0.001). CONCLUSIONS: This
      study has clinical implications as identification of indicators of lower physical
      and mental HRQoL outcomes for myocardial infarction patients allows for targeted
      counselling or coronary heart disease secondary prevention efforts. TRIAL
      REGISTRATION: Australian Clinical Trials Registry, Australian New Zealand
      Clinical Trials Registry, CTRN12607000595415.

PMID- 24020832
TI  - Hepatitis C patients on maintenance hemodialysis show complex immune disturbances
      in the peripheral blood.
AB  - Hepatitis C virus (HCV) infection is prevalent in patients with maintenance
      hemodialysis (HD). Although HCV affects the survival rate, antiviral treatment
      for HD patients is limited. Since impaired innate immunity has been proposed both
      in hepatitis C and in HD, we compared the immunologic features in periphery
      between these patients and controls. Thirty subjects were divided into four
      groups on the basis of HD and HCV infection. In peripheral blood mononuclear
      cells, NK subsets and their activation status were analyzed by flow cytometry.
      Cytokine productions were measured both in the culture supernatant and at the
      single cell level. In HCV-infected HD patients, CD56(dim) NK subset was decreased
      (13.1+/-3.7%, p=0.015) but had upregulated CD69 expression (10.4+/-4.2%, p=0.032)
      compared to the other groups. LPS effectively induced neither interferon (IFN)
      gamma nor tumor necrosis factor (TNF)-alpha in NK cells of both HCV-infected and 
      uninfected HD patients, while TNF-alpha-producing monocytes were increased in HCV
      infected HD patients as compared to the uninfected. These findings indicate that
      chronic HCV infection affects innate immunity independently of HD.

PMID- 24020833
TI  - Hydrogen water intake via tube-feeding for patients with pressure ulcer and its
      reconstructive effects on normal human skin cells in vitro.
AB  - BACKGROUND: Pressure ulcer (PU) is common in immobile elderly patients, and there
      are some research works to investigate a preventive and curative method, but not
      to find sufficient effectiveness. The aim of this study is to clarify the
      clinical effectiveness on wound healing in patients with PU by hydrogen-dissolved
      water (HW) intake via tube-feeding (TF). Furthermore, normal human dermal
      fibroblasts OUMS-36 and normal human epidermis-derived cell line HaCaT
      keratinocytes were examined in vitro to explore the mechanisms relating to
      whether hydrogen plays a role in wound-healing at the cellular level. METHODS:
      Twenty-two severely hospitalized elderly Japanese patients with PU were recruited
      in the present study, and their ages ranged from 71.0 to 101.0 (86.7 +/- 8.2)
      years old, 12 male and 10 female patients, all suffering from eating disorder and
      bedridden syndrome as the secondary results of various underlying diseases. All
      patients received routine care treatments for PU in combination with HW intake
      via TF for 600 mL per day, in place of partial moisture replenishment. On the
      other hand, HW was prepared with a hydrogen-bubbling apparatus which produces HW
      with 0.8-1.3 ppm of dissolved hydrogen concentration (DH) and -602 mV to -583 mV
      of oxidation-reduction potential (ORP), in contrast to reversed osmotic ultra
      pure water (RW), as the reference, with DH of < 0.018 ppm and ORP of +184 mV for
      use in the in vitro experimental research. In in vitro experiments, OUMS-36
      fibroblasts and HaCaT keratinocytes were respectively cultured in medium prepared
      with HW and/or RW. Immunostain was used for detecting type-I collagen
      reconstruction in OUMS-36 cells. And intracellular reactive oxygen species (ROS)
      were quantified by NBT assay, and cell viability of HaCaT cells was examined by
      WST-1 assay, respectively. RESULTS: Twenty-two patients were retrospectively
      divided into an effective group (EG, n = 12) and a less effective group (LG, n =
      10) according to the outcomes of endpoint evaluation and the healing criteria. PU
      hospitalized days in EG were significantly shorter than in LG (113.3 days vs.
      155.4 days, p < 0.05), and the shortening rate was approximately 28.1%. Either in
      EG or in LG, the reducing changes (EG: 91.4%; LG: 48.6%) of wound size
      represented statistically significant difference versus before HW intake (p <
      0.05, p < 0.001). The in vitro data demonstrate that intracellular ROS as
      quantified by NBT assay was diminished by HW, but not by RW, in ultraviolet-A
      (UVA)-irradiated HaCaT cells. Nuclear condensation and fragmentation had occurred
      for UVA-irradiated HaCaT cells in RW, but scarcely occurred in HW as demonstrated
      by Hoechst 33342 staining. Besides, under UVA-irradiation, either the
      mitochondrial reducing ability of HaCaT cells or the type-I collagen construction
      in OUMS-36 cells deteriorated in RW-prepared culture medium, but was retained in
      HW-prepared culture medium as shown by WST-1 assay or immunostain, respectively.
      CONCLUSIONS: HW intake via TF was demonstrated, for severely hospitalized elderly
      patients with PU, to execute wound size reduction and early recovery, which
      potently ensue from either type-I collagen construction in dermal fibroblasts or
      the promoted mitochondrial reducing ability and ROS repression in epidermal
      keratinocytes as shown by immunostain or NBT and WST-1 assays, respectively.

PMID- 24020835
TI  - Using a combined theoretical and experimental approach to understand the
      structure and dynamics of imidazolium-based ionic liquids/water mixtures. 1. MD
      simulations.
AB  - The structural and dynamic properties of 1-butyl-3-methylimidazolium bromide
      ([C4mim]Br)/water mixtures with different molar ratios have been investigated
      using classical molecular dynamics (MD) simulations, and the reliability of the
      results has been assessed by comparison with extended X-ray absorption fine
      structure experimental data. The analysis of the MD trajectories has highlighted
      the presence of a complex network of interactions among cations, anions, and
      water molecules, even if water molecules have been found to interact
      preferentially with the Br(-) anion. The existence of solvent-shared ion pairs
      has been detected in all of the investigated mixtures with one or more water
      molecules acting as a bridge between the cation and the anion, also when water is
      present in great excess ([C4mim]Br/water ratio of 1:200). The dynamic behavior of
      the systems has been characterized starting from the MD trajectories. Water
      molecules have been found to quicken the dynamics of the IL cations and anions,
      and acceleration involves all of the investigated motions. 

PMID- 24020834
TI  - Insulin induces proliferation and cardiac differentiation of P19CL6 cells in a
      dose-dependent manner.
AB  - Insulin is a peptide hormone produced by beta cells of the pancreas. The roles of
      insulin in energy metabolism have been well studied, with most of the attention
      focused on glucose utilization, but the roles of insulin in cell proliferation
      and differentiation remain unclear. In this study, we observed for the first time
      that 10 nmol/L insulin treatment induces cell proliferation and cardiac
      differentiation of P19CL6 cells, whereas 50 and 100 nmol/L insulin treatment
      induces P19CL6 cell apoptosis and blocks cardiac differentiation of P19CL6 cells.
      By using real-time polymerase chain reaction (PCR) and Western blotting analysis,
      we found that the mRNA levels of cyclin D1 and alpha myosin heavy chain (alpha
      MHC) are induced upon 10 nmol/L insulin stimulation and inhibited upon 50/100
      nmol/L insulin treatment, whereas the mRNA levels of BCL-2-antagonist of cell
      death (BAD) exists a reverse trend. The similar results were observed in P19CL6
      cells expressing GATA-6 or peroxisome proliferator-activated receptor alpha
      (PPARalpha). Our results identified the downstream targets of insulin, cyclin D1,
      BAD, alpha-MHC, and GATA-4, elucidate a novel molecular mechanism of insulin in
      promoting cell proliferation and differentiation.

PMID- 24020836
TI  - A critical test of the "tunneling and coupled motion" concept in enzymatic
      alcohol oxidation.
AB  - The physical mechanism of C-H bond activation by enzymes is the subject of
      intense study, and we have tested the predictions of two competing models for C-H
      activation in the context of alcohol dehydrogenase. The kinetic isotope effects
      (KIEs) in this enzyme have previously suggested a model of quantum mechanical
      tunneling and coupled motion of primary (1 degrees ) and secondary (2 degrees )
      hydrogens. Here we measure the 2 degrees  H/T KIEs with both H and D at the 1
      degrees  position and find that the 2 degrees  KIE is significantly deflated with
      D-transfer, consistent with the predictions of recent Marcus-like models of H
      transfer. The results suggest that the fast dynamics of H-tunneling result in a 1
      degrees  isotope effect on the structure of the tunneling ready state: the
      trajectory of D-transfer goes through a shorter donor-acceptor distance than that
      of H-transfer. 

PMID- 24020837
TI  - Low-temperature fabrication of mesoporous solid strong bases by using
      multifunction of a carbon interlayer.
AB  - Mesoporous solid strong bases are highly promising for applications as
      environmentally benign catalysts in various reactions. Their preparation attracts
      increasing attention for the demand of sustainable chemistry. In the present
      study, a new strategy was designed to fabricate strong basicity on mesoporous
      silica by using multifunction of a carbon interlayer. A typical mesoporous
      silica, SBA-15, was precoated with a layer of carbon prior to the introduction of
      base precursor LiNO3. The carbon interlayer performs two functions by promoting
      the conversion of LiNO3 at low temperatures and by improving the alkali-resistant
      ability of siliceous host. Only a tiny amount of LiNO3 was decomposed on pristine
      SBA-15 at 400  degrees C; for the samples containing >8 wt % of carbon, however,
      LiNO3 can be entirely converted to strongly basic sites Li2O under the same
      conditions. The guest-host redox reaction was proven to be the answer for the
      conversion of LiNO3, which breaks the tradition of thermally induced
      decomposition. More importantly, the residual carbon layer can prevent the
      siliceous frameworks from corroding by the newly formed strongly basic species,
      which is different from the complete destruction of mesostructure in the absence
      of carbon. Therefore, materials possessing both ordered mesostructure and strong
      basicity were successfully fabricated, which is extremely desirable for catalysis
      and impossible to realize by conventional methods. We also demonstrated that the
      resultant mesoporous basic materials are active in heterogeneous synthesis of
      dimethyl carbonate (DMC) and the yield of DMC can reach 32.4%, which is
      apparently higher than that over the catalysts without a carbon interlayer
      (<12.9%) despite the same lithium content. The strong basicity, in combination
      with the uniform mesopores, is believed to be responsible for such a high
      activity. 

PMID- 24020838
TI  - Development of a novel rhesus macaque model with an infectious R5 simian-human
      immunodeficiency virus encoding HIV-1 CRF08_BC env.
AB  - BACKGROUND: The CRF08_BC strain is one of the most predominant circulating Human
      immunodeficiency virus type 1 (HIV-1) strains in the Chinese pandemic. A simian
      human immunodeficiency virus (SHIV) encoding HIV-1 CRF08_BC env is highly
      desirable to evaluate candidate AIDS vaccines in non-human primates. METHODS:
      SHIV-KBQJ-12, which carries the envelope glycoprotein from QJ001, an infectious
      molecular clone of HIV-1 CRF08_BC, was generated. The replication capacity of
      SHIV-KBQJ-12 was determined both in human and rhesus macaque (Macaca mulatta)
      peripheral blood mononuclear cells (PBMCs) and in Chinese rhesus macaques.
      RESULTS: SHIV-KBQJ-12 replicated efficiently in human and macaque PBMCs and
      displayed a preference for CCR5 as an entry coreceptor. Productive infection of
      two macaques by intravenous inoculation with SHIV-KBQJ-12 was confirmed.
      CONCLUSIONS: SHIV-KBQJ-12 is an R5-tropic chimeric virus that can establish
      productive infection both in vitro and in vivo in Chinese rhesus macaques and
      will be useful to assess candidate HIV-1 CRF08_BC vaccines in China.

PMID- 24020839
TI  - Systematic review of anorectal varices.
AB  - AIM: Anorectal varices are an uncommon, but significant, source of bleeding in
      patients with portal hypertension. The aim of this article was to review
      systematically the available literature on the aetiology, clinical presentation
      and management of anorectal varices, and to suggest a simple treatment algorithm
      based on available evidence and local expertise. METHOD: A systematic literature
      search was carried out to identify articles on anorectal varices, and the search
      strategy identified 57 relevant references. The inclusion criteria included a
      consecutive cohort of patients having treatment for anorectal varices with
      details of success rates and the number of different techniques used. Exclusion
      criteria included papers published in languages other than English with no
      English version and results not reported separately for anorectal varices.
      RESULTS: Anorectal varices can occur in up to 89% of patients with portal
      hypertension, although the overall incidence in the general population is low.
      Diagnosis is best achieved with anoscopy or flexible sigmoidoscopy. The current
      evidence supports the use of local procedures, such as endoscopic band ligation,
      to arrest bleeding where feasible, with radiological or surgical procedures used
      in the event of failure. CONCLUSION: As there are no large series on this
      pathology, we present a systematic approach for the patient with anorectal
      varices.

PMID- 24020840
TI  - Influence of 4% icodextrin solution on peritoneal tissue response and adhesion
      formation.
AB  - BACKGROUND: Postoperative peritoneal adhesion formation following abdominal
      surgery remains a relevant surgical problem. The application of soluble physico
      chemical barriers like 4% icodextrin is one approach to protect the peritoneal
      surface from getting linked to adhesive scar. The aim of this study was to
      investigate the influence of 4% icodextrin on peritoneal tissue response both of
      visceral and parietal peritoneum, adhesion formation and wound healing. METHODS:
      40 rats were divided into two groups. After creation of an intraabdominal defect,
      either 4% icodextrin (Adept(r)) or sodium chloride was applied. Animals were
      sacrificed after 7 and 21 days. Adhesions were scored by an adhesion score.
      Furthermore, immunohistochemical investigations were conducted to determine the
      discrete influence of icodextrin on the parietal and visceral peritoneal tissue
      responses (CD68+ macrophages, CD3+ T-lymphocytes, vimentin for mesenchymal cells,
      HBME-1 for mesothelial cells, and as components of wound healing COX-2, C-myc,
      catenin). RESULTS: Postoperative peritoneal adhesions were predominantly present
      in the sodium chloride group as compared to the icodextrin group (14/19 (74%) vs.
      9/19 (47%); p = 0.048). The adhesion score however did not reveal any significant
      differences, (p = 0.614). Furthermore, the expression of vimentin in both the
      parietal and visceral peritoneum after 21 days was significantly lower in the
      icodextrin group than in the sodium chloride group (p = 0.038 and p = 0.028,
      respectively). No significant differences were observed for macrophages,
      lymphocytes, reperitonealisation or the expression of COX-2, C-myc or Catenin.
      CONCLUSIONS: The intraperitoneal application of 4% icodextrin reduces adhesion
      formation in comparison to sodium chloride. 4% icodextrin solution reduces the
      inflammatory and mesenchymal infiltrate in the wounded area, thus improving the
      ratio of mesothel cells to mesenchymal infiltrate. As demonstrated, icodextrin is
      able to ameliorate the local tissue response. Further experimental studies would
      be done to elaborate the impact on the early response of the adaptive immune
      system, which may then trigger the subsequent wound healing and tissue repair.

PMID- 24020841
TI  - Mercury reduction and cell-surface adsorption by Geobacter sulfurreducens PCA.
AB  - Both reduction and surface adsorption of mercuric mercury [Hg(II)] are found to
      occur simultaneously on G. sulfurreducens PCA cells under dark, anaerobic
      conditions. Reduction of Hg(II) to elemental Hg(0) initially follows a pseudo
      first order kinetics with a half-life of <2 h in the presence of 50 nM Hg(II) and
      10(11) cells L(-1) in a phosphate buffer (pH 7.4). Multiple gene deletions of the
      outer membrane cytochromes in this organism resulted in a decrease in reduction
      rate from ~0.3 to 0.05 h(-1), and reduction was nearly absent with heat-killed
      cells or in the cell filtrate. Adsorption of Hg(II) by cells is found to compete
      with, and thus inhibit, Hg(II) reduction. Depending on the Hg to cell ratio,
      maximum Hg(II) reduction was observed at about 5 * 10(-19) mol Hg cell(-1), but
      reduction terminated at a low Hg to cell ratio (<10(-20) mol Hg cell(-1)). This
      inhibitory effect is attributed to bonding between Hg(II) and the thiol (-SH)
      functional groups on cells and validated by experiments in which the sorbed
      Hg(II) was readily exchanged by thiols (e.g., glutathione) but not by carboxylate
      compounds such as ethylenediamine-tetraacetate (EDTA). We suggest that coupled
      Hg(II)-cell interactions, i.e., reduction and surface binding, could be important
      in controlling Hg species transformation and bioavailability and should therefore
      be considered in microbial Hg(II) uptake and methylation studies. 

PMID- 24020842
TI  - Effects of various mixing techniques on physical properties of white mineral
      trioxide aggregate.
AB  - INTRODUCTION: The aim of this study was to evaluate the effects of three
      different mixing techniques on surface microhardness, initial setting time, and
      phase formation of white mineral trioxide aggregate. METHODS: Twenty-one
      cylindrical glass tubes were selected and divided into three groups of seven in
      each (n = 7). White mineral trioxide aggregate (WMTA) in groups A, B, and C were
      mixed by conventional, trituration, and ultrasonic techniques, respectively.
      Cements were mixed and packed into the glass tubes and incubated at 37 degrees C
      for 3 days. After incubation, samples were subjected to microhardness evaluation,
      and four specimens from each group were prepared and observed under a scanning
      electron microscopy and X-ray diffraction. For setting time assessment, WMTA was
      mixed in three parts again, and Gilmore needle test was performed until the
      initial setting time of cement. Data were analyzed by one-way anova and post hoc
      Tukey's test. RESULTS: Samples mixed by trituration technique significantly
      showed the highest microhardness (P < 0.001) and the lowest setting time, while
      the ultrasonically mixed specimens significantly revealed the highest setting
      time in comparison with other groups (P < 0.001). Samples mixed by trituration
      technique showed the highest uniformity in the bulk and highest amount of
      hydrated calcium silicate (CS) phases, while the lowest value was observed in
      ultrasonically mixed cements, which also showed the highest amount of anhydrated
      CS phases. CONCLUSION: Trituration and conventional techniques were more suitable
      mixing methods for mineral trioxide aggregate in comparison with ultrasonic
      technique. Trituration resulted in better hydration and crystallization, which
      prevents clustering of powder and reduces voids and setting time of mixed cement.

PMID- 24020844
TI  - Clinicopathologic features of an infant with generalized congenital epithelioid
      blue nevi.
AB  - Since epithelioid blue nevus (EBN) was 1st described in patients with Carney
      complex, 49 sporadic EBN cases, including 4 congenital EBN, have been reported.
      We present a 2-month-old healthy female with more than 1000 congenital EBN on the
      entire body. Skin biopsy revealed many nevus nests located in the upper dermis
      and a few nests extended around the sweat ducts and hair follicles in the middle
      and lower dermis. The heavily pigmented melanocytes were substantially
      epithelioid and occasionally spindle cells, admixed with melanophages.
      Immunohistochemistry revealed strong staining for S-100 and HMB-45 but weak or
      moderate staining for Melan-A in dermal melanocytes after melanin bleaching with
      potassium permanganate and oxalic acid prior to incubation with the primary
      antibody. A diagnosis of congenital EBN was made based on clinicopathologic and
      immunopathologic findings.

PMID- 24020843
TI  - Synthetic chondramide A analogues stabilize filamentous actin and block invasion
      by Toxoplasma gondii.
AB  - Apicomplexan parasites such as Toxoplasma gondii rely on actin-based motility to
      cross biological barriers and invade host cells. Key structural and biochemical
      differences in host and parasite actins make this an attractive target for small
      molecule inhibitors. Here we took advantage of recent advances in the synthesis
      of cyclic depsipeptide compounds that stabilize filamentous actin to test the
      ability of chondramides to disrupt growth of T. gondii in vitro. Structural
      modeling of chondramide A (2) binding to an actin filament model revealed
      variations in the binding site between host and parasite actins. A series of 10
      previously synthesized analogues (2b-k) with substitutions in the beta-tyrosine
      moiety blocked parasite growth on host cell monolayers with EC50 values that
      ranged from 0.3 to 1.3 MUM. In vitro polymerization assays using highly purified
      recombinant actin from T. gondii verified that synthetic and natural product
      chondramides target the actin cytoskeleton. Consistent with this, chondramide
      treatment blocked parasite invasion into host cells and was more rapidly
      effective than pyrimethamine, a standard therapeutic agent. Although the current
      compounds lack specificity for parasite vs host actin, these studies provide a
      platform for the future design and synthesis of synthetic cyclic peptide
      inhibitors that selectively disrupt actin dynamics in parasites.

PMID- 24020845
TI  - Silencing of GLUT-I inhibits sensitization of oral cancer cells to cisplatin
      during hypoxia.

PMID- 24020846
TI  - Effect of mitochondrial, APOE, ACE and NOS3 gene polymorphisms on cardiovascular
      risk factors among the Vaqueiros de Alzada, a Northern Spain human isolate.
AB  - BACKGROUND: The Vaqueiros de Alzada are a human isolate from Asturias, a Northern
      Spain region. Several hypotheses have been proposed to explain the origin of
      Vaqueiros. METHODS AND RESULTS: To determine whether the Vaqueiros and non
      Vaqueiros from the same region have different genetic backgrounds, this study
      analysed nine mtDNA polymorphisms that define the common European mitochondrial
      haplogroups in a cohort of Vaqueiros (n = 60) and non-Vaqueiros (n = 110).
      Haplogroup H was the most frequent in Vaqueiros (42%) and non-Vaqueiros (46%). A
      total of 37% Vaqueiros were H1, compared to 31% of the non-Vaqueiros. This study
      also genotyped the two groups for three polymorphisms at the NOS3. APOE and ACE
      genes, that have previously been linked to risk of cardiovascular diseases.
      Allele and genotype frequencies did not differ between Vaqueiros and non
      Vaqueiros. In addition, none of these polymorphisms were related to risk of
      hypertension, diabetes or hypercholesterolaemia in the two groups. CONCLUSION:
      The data suggested that Vaqueiros share the main haplogroup distribution as their
      non-Vaqueiros neighbours and other Cantabrian populations. In addition, no effect
      of the mitochondrial, NOS3. APOE and ACE polymorphisms on cardiovascular risk
      factors was observed.

PMID- 24020847
TI  - A multifunctional theranostic platform based on phthalocyanine-loaded dendrimer
      for image-guided drug delivery and photodynamic therapy.
AB  - Owing to the outstanding near-infrared (NIR) optical properties, phthalocyanines
      (Pc) have promising potential as theranostic agents for fluorescence image-guided
      drug delivery and noninvasive treatment of deep tumors by photodynamic therapy
      (PDT). Nevertheless, clinical application of phthalocyanines is substantially
      limited by poor water solubility, aggregation and insufficient selectivity for
      cancer cells. To address these issues, we have developed a novel dendrimer-based
      theranostic platform for tumor-targeted delivery of phthalocyanines. The
      preparation procedure involved the modification of the Pc molecule with a
      hydrophobic linker, which significantly enhances physical encapsulation of the
      hydrophobic drug into a generation 4 polypropylenimine (PPI G4) dendrimer. In
      order to improve biocompatibility and tumor-targeted delivery, the surface of the
      resulting Pc-PPIG4 complexes was additionally modified with poly(ethylene glycol)
      (PEG) and luteinizing hormone-releasing hormone (LHRH) peptide, respectively. The
      developed nanocarriers have an average diameter of 62.3 nm and narrow size
      distribution with a polydispersity index of 0.100. The drug encapsulation
      efficiency was 20% w/w, and the synthesized phthalocyanine derivative entrapped
      in the dendrimer-based nanocarrier exhibits a distinct NIR absorption (700 nm)
      and fluorescence emission (710 and 815 nm), required for an efficient PDT and
      fluorescence imaging. It was demonstrated that subcellular localization in vitro
      and organ distribution in vivo of the developed nanocarrier can be determined
      based on the intrinsic fluorescence properties of encapsulated phthalocyanine,
      validating its role as an imaging agent. The imaging experiments revealed that
      the LHRH targeted nanocarrier is capable of an efficient internalization into
      cancer cells as well as tumor accumulation when intravenously administered into
      mice. Finally, the prepared formulation exhibited low dark cytotoxicity (IC50=28
      MUg/mL) while light irradiation of the cancer cells transfected with the
      developed theranostic agents resulted in significant PDT effects (IC50=0.9
      MUg/mL) through excessive generation of toxic reactive oxygen species. Thus, the
      obtained results demonstrated significant potential of the designed dendrimer
      based nanocarrier as an efficient NIR theranostic agent.

PMID- 24020848
TI  - PTSD in the armed forces: what have we learned from the recent cohort studies of
      Iraq/Afghanistan?
AB  - Post-traumatic stress disorder (PTSD) was formally recognised as a psychiatric
      disorder in 1980, largely in response to America's attempts to make sense of the
      costs of the Vietnam war [Wessely, S., & Jones, E. (2004). Psychiatry and the
      'lessons of Vietnam': What were they, and are they still relevant? War & Society,
      22(1), 89-103.]. Interestingly, all of this occurred without much contribution
      from epidemiology, which came later (Wessely & Jones, 2004). This cannot be said
      of the current conflicts, where from the outset there has been a focus of
      attention on the epidemiology of PTSD in those who served in either Iraq or
      Afghanistan, even whilst the conflicts were ongoing. In this editorial, we focus
      on this recent epidemiological contribution to the understanding of PTSD in
      military personnel. 

PMID- 24020849
TI  - A national survey of adult safeguarding in NHS mental health services in England
      and Wales.
AB  - BACKGROUND: Following the introduction of the No Secrets (Department of Helath,
      (2000). No Secrets: Guidance on Developing and Implementing Multi-agency Policies
      and Procedures to Protect Vulnerable Adults from Abuse. London: HMSO) guidance,
      the implementation and development of adult safeguarding practices and procedures
      across national services has become an ongoing endeavour. Despite existing
      research highlighting practice improvements in many services, NHS mental health
      services are persistently criticised for their lack of engagement with the
      national adult safeguarding agenda ( Department of Health (2009) . Safeguarding
      Adults: Report on the Consultation on the Review of 'No Secrets'. London: HMSO).
      AIM: To investigate the organisational structure, implementation and development
      of adult safeguarding in NHS mental health services. METHOD: A cross-sectional
      survey was distributed on-line to 79 (72 NHS Mental Health Trusts in England and
      seven Health Boards in Wales) NHS mental health services. Results Thirty-three
      completed surveys were returned, yielding a response rate of 41%. The results
      highlight adequate arrangements for adult safeguarding in many services; however,
      it appears implementation is in its initial stages. Responses suggest that staff
      attitudes and uptake of training are the greatest barrier to practice; however,
      barriers are also indicated at a strategic and operational level. CONCLUSION: The
      importance of adult safeguarding must be recognised at all levels and there is an
      immediate need for improvement to staff training and engagement to ensure future
      effective practice in this area.

PMID- 24020850
TI  - The locked psychiatric ward: hotel or detention camp for people with dual
      diagnosis.
AB  - BACKGROUND: The concepts of autonomy and liberty are established goals in mental
      health care; however, involuntary commitment is used towards people with mental
      health and substance abuse problems (dual diagnosis). AIMS: To explore how
      patients and staff act in the context of involuntary commitment, how interactions
      are described and how they might be interpreted. METHOD: Ethnographic methodology
      in a locked psychiatric ward in Norway. RESULTS: Two parallel images emerged: (a)
      The ward as a hotel. Several patients wanted a locked ward for rest and safety,
      even when admission was classified as involuntary. The staff was concerned about
      using the ward for real treatment of motivated people, rather than merely as a
      comfortable hotel for the unmotivated. (b) The ward as a detention camp. Other
      patients found involuntary commitment and restrictions in the ward as a kind of
      punishment, offending them as individuals. Contrary, the staff understood people
      with dual diagnoses more like a generalized group in need of their control and
      care. CONCLUSION: Patients and staff have different perceptions of involuntary
      commitment. Based on the patients' points of view, mental health care ought to be
      characterized by inclusion and recognition, treating patients as equal citizens
      comparable to guests in a hotel.

PMID- 24020851
TI  - Recovery in involuntary psychiatric care: is there a gender difference?
AB  - BACKGROUND: Research on recovery from mental illness and the influence of
      compulsory psychiatric institutional care has revealed the complexity of this
      concept. There is also limited knowledge regarding the impact of gender-role
      expectations in these contexts, and how such expectations may influence both the
      care and individuals' recovery processes. AIM: To explore women's and men's
      perceptions of the impact of compulsory inpatient care on recovery from severe
      mental illness. METHOD: Grounded theory was used to analyse 30 first-person
      accounts of recovery from mental illness, elicited via interviews with
      individuals who had been compulsorily treated in hospital and diagnosed with a
      severe mental illness. RESULTS: Inpatient care at an early stage was crucial for
      the informants' recovery. However, there was ambivalence in their perceptions of
      the impact of compulsory inpatient care. The narratives confirmed gender
      differences as well as gender stereotypes. CONCLUSIONS: The results have
      implications for recovery research, in that they emphasise the importance of
      understanding recovery as a gender-influenced process.

PMID- 24020852
TI  - Case series of physical examinations on psychiatric inpatients: Influence of a
      structured form on the quality of documentation.
AB  - BACKGROUND: There is a strong association between mental disorder and poor
      physical health. However, research indicates that the standard of physical
      examinations performed on psychiatric inpatients is not good. AIMS: This study
      aimed to assess the completeness of the physical examinations performed by
      psychiatric trainees on an acute psychiatric inpatient unit. METHOD: A
      retrospective analysis of 236 sets of inpatient case notes was performed. The
      quality of the documentation was assessed using a 50-point scoring system based
      on the presence or absence of reference to various items of examination. RESULTS:
      Eighty-five percent of the patients received a complete examination and 13% were
      not examined at all. The mean points score was only 20 out of 50, indicating that
      the overall standard of documentation was quite low. However, when a proforma was
      used rather than free text documentation, significantly more information was
      recorded. CONCLUSIONS: Most psychiatric patients are not receiving a thorough
      physical examination. An essential first step to address the problem would be to
      divide physical examinations into three categories according to the psychiatric
      setting and reach a consensus on a gold standard for each type. Standards could
      also be improved by the more widespread use of a well-designed proforma and
      greater supervision of psychiatric trainees' performance in this area.

PMID- 24020853
TI  - Suicide prevention: evaluation of a pilot intervention in a primary care context.
AB  - BACKGROUND: From July 2008 to June 2011, 19 Australian Divisions of General
      Practice piloted specialist services for consumers at risk of suicide within a
      broader primary mental health program. General practitioners and other mental
      health staff referred suicidal consumers to specially trained mental health
      professionals for intensive, time-limited care. AIMS: To report the findings from
      an evaluation of the pilot. METHOD: Data sources included a purpose-designed
      minimum data set, which collated consumer-level and session-level data, and a
      series of structured telephone interviews conducted with Divisional project
      officers, referrers and mental health professionals. RESULTS: There were 2312
      referrals to the pilot; 2070 individuals took up the service. The pilot reached
      people who may not otherwise have had access to psychological care; over half of
      those who received services were on low incomes and about one-third had not
      previously accessed mental health care. Project officers, referrers and mental
      health professionals were all positive about the pilot and commented that it was
      meeting a previously unmet need. Consumers appeared to benefit, showing
      significant improvements in outcomes. CONCLUSION: This evaluation provides
      supportive evidence for the effectiveness of a suicide prevention intervention
      delivered by specially trained mental health professionals in a primary mental
      health environment.

PMID- 24020854
TI  - Staff and patient experience of improving access to psychological therapy group
      interventions for anxiety and depression.
AB  - BACKGROUND: The improving access to psychological therapy (IAPT) initiative aims
      to provide widespread evidence-based psychological treatments for common mental
      health problems in the UK. Individual services have implemented National
      Institute for Clinical Excellence guidelines in various ways; some provide group
      based therapy, whilst others do not. AIMS: The study investigates how patients
      and staff experience group-based therapy, what they find helpful and where
      improvements can be made. METHOD: Forty-five semi-structured interviews were
      undertaken with staff and patients in three IAPT services. Framework analysis was
      used to analyse comments relating to patient experience in group-based treatment.
      RESULTS: The study found that patients can feel isolated with their symptoms and
      group-based interventions can normalise the illness, reducing stress. Individuals
      experience benefits and, in some cases, difficulties, in different ways. Some
      patients hear of the strategies that others have found useful, and observe
      others' progress, which may bring hope for their own recovery. CONCLUSIONS: IAPT
      group-based interventions appear to aid recovery in different ways to one-to-one
      therapy, by normalising mental illness and increasing social contact. Greater
      understanding of the factors operating in group-based interventions might
      increase attendance and recovery facilitated by IAPT group interventions.

PMID- 24020856
TI  - Temperature-dependent Henry's law constants of atmospheric organics of biogenic
      origin.
AB  - There have been growing interests in modeling studies to understand oxidation of
      volatile organic compounds in the gas phase and their mass transfer to the
      aqueous phase for their potential roles in cloud chemistry, formation of
      secondary organic aerosols, and fate of atmospheric organics. Temperature
      dependent Henry's law constants, key parameters in the atmospheric models to
      account for mass transfer, are often unavailable. In the present work, we
      investigated gas-liquid equilibriums of isoprene, limonene, alpha-pinene, and
      linalool using a bubble column technique. These compounds, originating from
      biogenic sources, were selected for their implications in atmospheric cloud
      chemistry and secondary organic aerosol formation. We reported Henry's law
      constants (K(H)), first order loss rates (k), and gas phase diffusion
      coefficients over a range of temperatures relevant to the lower atmosphere (278
      298 K) for the first time. The measurement results of K(H) values for isoprene,
      limonene, alpha-pinene, and linalool at 298 K were 0.036 +/- 0.003; 0.048 +/-
      0.004; 0.029 +/- 0.004; and 21.20 +/- 0.30 mol L(-1) atm(-1), respectively. The
      fraction for these compounds in stratocumulus and cumulonimbus clouds at 278 K
      were also estimated in this work (isoprene, 1.0 * 10(-6), 6.8 * 10(-6); limonene,
      1.5 * 10(-6), 1.0 * 10(-5); alpha-pinene, 4.5 * 10(-7), 3.1 * 10(-6); and
      linalool, 6.2 * 10(-4), 4.2 * 10(-3)). Our measurements in combination with
      literature results indicated that noncyclic alkenes could have smaller K(H)
      values than those of cyclic terpenes and that K(H) values may increase with an
      increasing number of double bonds. It was also shown that estimated Henry's law
      constants and their temperature dependence based on model prediction can differ
      from experimental results considerably and that direct measurements of
      temperature-dependent Henry's law constants of atmospheric organics are necessary
      for future work.

PMID- 24020857
TI  - How to take care of nurses in your organization: two types of exchange
      relationships compared.
AB  - AIM: To explore the relationships between climate for well-being, economic and
      social exchange, affective ward commitment and job strain among nurses in the
      Netherlands. BACKGROUND: This study focuses on the immediate work environment of
      nurses by exploring the way nurse perceptions about the extent to which the ward
      values and cares for their welfare influence their levels of affective ward
      commitment and job strain. Second, this study extends previous research on
      exchange relationships by examining the potential differential impact of social
      and economic exchange relationships on commitment and job strain. DESIGN: A cross
      sectional survey among nurses. METHODS: The study was conducted in the
      Netherlands in 2011. Validated measures of climate for well-being, social
      exchange, economic exchange, ward commitment and job strain were used. Hypotheses
      were tested using regression analyses. MacKinnon et al.'s (2007) guidelines to
      assess mediation were used. RESULTS: The response rate was 41% (271
      questionnaires). The results show that climate for well-being positively
      influences social exchange relationships, which are in turn associated with
      enhanced ward commitment and reduced strain. Climate for well-being negatively
      influences evaluations of economic exchange, which are in turn negatively related
      to ward commitment. CONCLUSION: This study shows that nurses use the information
      available in their immediate work environment to evaluate their exchange
      relationship with the organization. Second, the findings point towards the
      importance of economic and social exchange relationships as a mechanism between
      climate for well-being on the one hand and affective ward commitment and job
      strain on the other hand.

PMID- 24020858
TI  - Ultrasmall fluorescent ion-exchanging nanospheres containing selective
      ionophores.
AB  - We present a convenient precipitation procedure to fabricate ultrasmall
      fluorescent ion-selective nanosensors that operate on the basis of bulk ion
      exchange sensing principles. The nanosphere matrix is composed of bis(2
      ethylhexyl) sebacate (DOS) and a triblock copolymer Pluronic((r)) F-127, which
      also functions as a surfactant to stabilize the nanoparticle. The particles can
      be prepared easily in large quantity without resorting to further complicated
      purification. Dynamic light scattering shows that these particles have a
      monodisperse size distribution with an average diameter of ~40 nm, suggesting
      that the nanoparticles are among the smallest ionophore-based ion-selective
      nanosensors reported to date. A newly reported oxazinoindoline (Ox) as well as a
      Nile blue derivative (chromoionophore I) was used as a chromoionophore. Na(+)-
      and H(+)-selective nanospheres were characterized by absorbance and fluorescence
      spectroscopy. Owing to the very small size of the nanospheres, the suspension
      containing the particles is transparent. In the additional presence of the pH
      indicator HPTS, spectroscopic interrogation of pH and Na(+) in the same sample
      was demonstrated. As an example, the nanospheres were used to measure the Na(+)
      level in commercial mineral waters, and the results showed good agreement with
      atomic absorption spectroscopy (AAS). 

PMID- 24020859
TI  - Treating clients with Asperger's syndrome and autism.
AB  - Asperger's syndrome (AS) is a form of autism spectrum disorder (ASD) affecting
      many individuals today. Although neurobiological correlates for AS have been
      identified, like many ASDs, AS is not completely understood. AS as a distinct
      disorder is also not universally accepted and in the DSM-5 AS is not considered a
      separate nosological entity. In contrast to some other ASDs, individuals with AS
      are commonly characterized by having standard or higher than average
      intelligence, yet difficulties in social skills and communication can present
      challenges for these individuals in everyday functioning. Counseling a person
      with AS or autism presents a unique challenge for the mental health care
      provider. We have compiled this review consisting of some recent ideas regarding
      counseling the client with AS with the goal of providing some clinical insights
      and practical clues. Although the focus of the present paper is largely on AS,
      many of these strategies could also apply to individuals with high-functioning
      autism (HFA). 

PMID- 24020861
TI  - Ethical issues in human reproduction: Catholic perspectives.
AB  - The catholic perspective in human reproduction is based on the concept that the
      human being is to be respected and treated as a person from the moment of
      conception. In this paper the ethical implications derived from such a principle
      are discussed.

PMID- 24020862
TI  - Valsalva manoeuver, intra-ocular pressure, cerebrospinal fluid pressure, optic
      disc topography: Beijing intracranial and intra-ocular pressure study.
AB  - PURPOSE: To assess whether a Valsalva manoeuver influences intra-ocular pressure
      (IOP), cerebrospinal fluid pressure (CSF-P) and, by a change in the trans-laminar
      cribrosa pressure difference, optic nerve head morphology. METHODS: In the first
      part of the study, 20 neurological patients (study group 'A') underwent
      measurement of IOP and lumbar CSF-P measurement in a lying position before and
      during a Valsalva manoeuver. In the second study part, 20 healthy subjects (study
      group 'B') underwent ocular tonometry and confocal scanning laser tomography of
      the optic nerve head before and during a Valsalva manoeuver. RESULTS: During the
      Valsalva manoeuver in study group 'A', the increase in CSF-P by 10.5 +/- 2.7 mmHg
      was significantly (p < 0.001) higher than the increase in IOP by 1.9 +/- 2.4
      mmHg. The change in CSF-P was not significantly (p = 0.61) correlated with the
      change in IOP. During the Valsalva manoeuver in study group 'B', IOP increased by
      4.5 +/- 4.2 mmHg and optic cup volume (p < 0.001), cup/disc area ratio (p =
      0.02), cup/disc diameter ratio (p = 0.03) and maximum optic cup depth (p = 0.01)
      significantly decreased, while neuroretinal rim volume (p = 0.005) and mean
      retinal nerve fibre layer thickness (p = 0.02) significantly increased.
      CONCLUSIONS: The Valsalva manoeuver-associated short-term increase in CSF-P was
      significantly larger than a simultaneous short-term increase in IOP. It led to a
      Valsalva manoeuver-associated decrease or reversal of the trans-laminar cribrosa
      pressure difference, which was associated with a change in the three-dimensional
      optic nerve head morphology: optic cup-related parameters decreased and
      neuroretinal rim-related parameters enlarged. These findings may be of interest
      for the pathogenesis of glaucomatous optic neuropathy.

PMID- 24020860
TI  - Modeling the within-host dynamics of HIV infection.
AB  - The new field of viral dynamics, based on within-host modeling of viral
      infections, began with models of human immunodeficiency virus (HIV), but now
      includes many viral infections. Here we review developments in HIV modeling,
      emphasizing quantitative findings about HIV biology uncovered by studying acute
      infection, the response to drug therapy and the rate of generation of HIV
      variants that escape immune responses. We show how modeling has revealed many
      dynamical features of HIV infection and how it may provide insight into the
      ultimate cure for this infection. 

PMID- 24020863
TI  - An examination of generalized anxiety disorder and dysthymic disorder by latent
      class analysis.
AB  - BACKGROUND: The nosological status of generalized anxiety disorder (GAD) versus
      dysthymic disorder (DD) has been questioned. The aim of this study was to examine
      qualitative differences within (co-morbid) GAD and DD symptomatology. METHOD:
      Latent class analysis was applied to anxious and depressive symptomatology of
      respondents from three population-based studies (2007 Australian National Survey
      of Mental Health and Wellbeing; National Comorbidity Survey Replication; and
      Netherlands Mental Health Survey and Incidence Study-2; together known as the
      Triple study) and respondents from a multi-site naturalistic cohort [Netherlands
      Study of Depression and Anxiety (NESDA)]. Sociodemographics and clinical
      characteristics of each class were examined. RESULTS: A three-class (Triple
      study) and two-class (NESDA) model best fitted the data, reflecting mainly
      different levels of severity of symptoms. In the Triple study, no division into a
      predominantly GAD or DD co-morbidity subtype emerged. Likewise, in spite of the
      presence of pure GAD and DD cases in the NESDA sample, latent class analysis did
      not identify specific anxiety or depressive profiles in the NESDA study. Next,
      sociodemographics and clinical characteristics of each class were examined.
      Classes only differed in levels of severity. CONCLUSIONS: The absence of
      qualitative differences in anxious or depressive symptomatology in empirically
      derived classes questions the differentiation between GAD and DD.

PMID- 24020865
TI  - Biological markers in schizophrenia and autism.

PMID- 24020864
TI  - Use of a highly-sensitive cardiac troponin I assay in a screening population for
      hypertrophic cardiomyopathy: a case-referent study.
AB  - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a genetic condition, and
      relatives of affected persons may be at risk. Cardiac troponin biomarkers have
      previously been shown to be elevated in HCM. This study examines the new highly
      sensitive cardiac troponin I (hsTnI) assay in a HCM screening population.
      METHODS: Nested case-control study of consecutive HCM sufferers and their
      relatives recruited from May 2010 to September 2011. After informed consent,
      participants provided venous blood samples and clinical and echocardiographic
      features were recorded. Associations between the natural log (ln) of the
      contemporary troponin I (cTnI) and hsTnI assays and markers of cardiac
      hypertrophy were examined. Multiple regression models were fitted to examine the
      predictive ability of hsTnI for borderline or definite HCM. RESULTS: Of 107
      patients, 24 had borderline and 19 had definite changes of HCM. Both TnI assays
      showed significant, positive correlations with measures of cardiac muscle mass.
      After age and sex adjustment, the area under the receiver operator characteristic
      (AUROC) curve for the outcome of HCM was 0.78, 95% CI [0.65, 0.90], for
      ln(hsTnI), and 0.66, 95% CI [0.51, 0.82], for ln(cTnI) (p=0.11). Including the
      hsTnI assay in a multiple-adjusted "screening" model for HCM resulted in a non
      significant improvement in both the AUROC and integrated discrimination index.
      CONCLUSIONS: Both cTnI and hsTnI show a graded, positive association with
      measures of cardiac muscle mass in persons at risk of HCM. Further studies will
      be required to evaluate the utility of these assays in ECG- and symptom-based
      identification of HCM in at-risk families.

PMID- 24020866
TI  - Pharmacological challenge with naloxone and cue exposure in alcohol dependence:
      results of a randomized, double-blind placebo-controlled trial.
AB  - OBJECTIVES: Animal and clinical studies implicated opioid dysfunction in the
      pathogenesis of alcohol abuse and dependence. The pi-opioid antagonist naltrexone
      reduces craving, eventually modulated by hypothalamic-pituitary-adrenal axis.
      Altered cortisol response to opioid receptor blockade not only in alcohol
      dependent persons, but also in persons with a family history of alcohol
      dependency was reported. METHODS: Twenty patients with alcohol dependence who had
      undergone detoxification were recruited. Naloxone (3.2 mg/70 kg body weight)
      having a very similar receptor profile to naltrexone and placebo were
      administered in cross-over fashion on two separate days 48 h apart. Mood and
      craving was assessed with well-established instruments (Alcohol Craving
      Questionnaire (ACQ), Profile of Mood Scale (POMS)). Both patients and raters were
      blind to all treatments. Twelve patients were first treated with naloxone, eight
      were first treated with placebo. RESULTS: No significant differences were found
      between the placebo and naloxone groups according to ACQ and POMS. Cortisol
      levels were significantly higher in naloxone group. CONCLUSIONS: We could not
      replicate the result, that blocking of the endogenous opioid system leads to
      reduced craving in alcohol-dependent individuals, while increase of cortisol
      after naloxone challenge is the expected biological effect of opioid receptor
      blockade on the hypothalamic-pituitary-adrenal (HPA) axis.

PMID- 24020867
TI  - Abdominal obesity with hypertriglyceridaemia, lipoprotein(a) and apolipoprotein A
      I determine marked cardiometabolic risk.
AB  - BACKGROUND: Risks for coronary heart disease (CHD) and diabetes (T2DM) of the
      'hypertriglyceridemic waist' phenotype (HtgW) warrant further investigation. We
      studied this issue and whether partial proinflammatory conversion of
      apolipoprotein (apo) A-I by lipoprotein(a) [Lp(a)] is a codeterminant. MATERIALS
      AND METHODS: In a population-based prospective study, 1328 Turkish adults were
      analysed in four groups by the presence of abdominal obesity and elevated
      triglycerides (Htg). RESULTS: LDL-cholesterol levels, significantly elevated in
      isolated Htg, were lower in HtgW, yet significantly higher apoB and complement C3
      values existed in women with HtgW in whom also the lowest Lp(a) values prevailed.
      Lp(a) was linearly associated, more strongly in HtgW than in the remaining
      groups, with apoB and, in women inversely, with gamma-glutamyltransferase.
      Incident HtgW was predicted, not in men, but in women inversely by Lp(a) (OR 0.80
      [95%CI 0.65; 0.97]), regardless of adjustment for relevant confounders. After
      adjustment for conventional risk factors, HtgW (OR 2.84) and high apoA-I/HDL-C
      ratio (OR 1.50) were significantly and additively associated with combined
      prevalent and incident CHD risk. High apoA-I and low HDL-cholesterol levels
      interacted therein in women. Type-2 diabetes was strongly predicted by HtgW,
      mediated in men by high apoA-I/HDL-C ratio. CONCLUSION: HtgW is associated with
      excess inflammatory markers, is predicted in women paradoxically by lower
      circulating Lp(a) and is associated in both sexes with marked excess
      cardiometabolic risk to which high apoA-I/HDL-C ratio contributes additively.
      These findings are consistent in women with apoA-I being oxidized via aggregation
      to Lp(a).

PMID- 24020868
TI  - Differences in the readiness of guilty and informed innocent examinees to
      cooperate on the Guilty Action Test.
AB  - A mock crime experiment was designed in which 100 participants were randomly
      assigned to five conditions: four experimental conditions in a 2 * 2 factorial
      design (two guilt conditions-guilty or informed innocents, crossed with two
      incentive level conditions-with or without a promised reward for proving
      innocence), and one control condition of uninformed innocents. Along with the
      common dependent polygraph measures, attitudes towards cooperating with the test
      were assessed. Results indicated that the informed innocents preferred to
      cooperate whereas guilty participants preferred to try and obstruct the test.
      These tendencies were amplified among participants who were promised a reward.
      The cooperative choice attenuated electrodermal responses to the critical items.
      Respiration measures were sensitive to the incentive level manipulation.
      Implications of the results for future research and for actual detection of
      information tests were discussed. 

PMID- 24020869
TI  - Safety, effectiveness, and cost of long-acting versus intermediate-acting insulin
      for type 1 diabetes: protocol for a systematic review and network meta-analysis.
AB  - BACKGROUND: Type 1 diabetes mellitus (T1DM) causes progressive destruction of
      pancreatic beta cells leading to absolute insulin deficiency. Treatment of T1DM
      requires insulin, and some evidence suggests that longer acting insulin analogues
      might have a higher effectiveness and greater safety profile compared to
      intermediate-acting insulin. Our objective is to evaluate the comparative
      effectiveness, safety, and cost of long-acting insulin versus intermediate-acting
      insulin through a systematic review and network meta-analysis. DESIGN/METHODS:
      Studies examining long-acting versus intermediate-acting insulin or placebo
      preparations for adult T1DM patients will be included. The primary outcome is
      glycosylated hemoglobin (A1C), and secondary outcomes include emergency
      department and physician visits, hospital admissions, weight gain, quality of
      life, microvascular complications (e.g., retinopathy), macrovascular
      complications (e.g., cardiovascular disease), all-cause mortality, incident
      cancers, and cost. We will include experimental [randomized clinical trials
      (RCTs), quasi-RCTs, non-RCTs], quasi-experimental (controlled before-after,
      interrupted time series), observational (cohort), and cost studies, of any
      duration of follow-up, conducted during all time periods, and disseminated in any
      language.We will conduct comprehensive searches of electronic databases from
      inception onwards, including MEDLINE, Cochrane Central Register of Controlled
      Trials, and EMBASE. We will also search for difficult to locate and unpublished
      literature by searching dissertation databases, public health organization
      websites, and trial registries. After a calibration exercise using our
      eligibility criteria and data abstraction forms, two reviewers will screen all
      citations, full-text articles, and abstract data in duplicate. Conflicts will be
      resolved by team discussion. Using a similar process, the Cochrane Effective
      Practice and Organization of Care Risk of Bias tool will be used to appraise the
      risk of bias of experimental and quasi-experimental studies, while the Newcastle
      Ottawa Scale will be used to assess the methodological quality of cohort studies.
      If feasible and appropriate, we will conduct a random effects meta-analysis, as
      well as a network meta-analysis. DISCUSSION: Our systematic review will be of
      utility to healthcare providers, policy-makers, T1DM patients and family members
      regarding treatment options of long-acting versus intermediate-acting insulin
      preparations. TRIAL REGISTRATION: PROSPERO registry number: CRD42013003610.

PMID- 24020870
TI  - Delivery of sevoflurane to dogs using a Stephens anaesthetic machine.
AB  - OBJECTIVE: To investigate the sevoflurane concentrations produced within the
      Stephens anaesthetic machine circuit (vaporizer in-circle system) at different
      fresh gas flow rates (FGFRs), temperatures, vaporizer settings and vaporizer
      sleeve positions when used to anaesthetize dogs of different body sizes. STUDY
      DESIGN: Experimental non-blinded studies. ANIMALS: Eighteen mixed breed dogs,
      weights 4-39 kg. METHODS: Anaesthetic induction with propofol was followed by
      maintenance with sevoflurane in oxygen via the Stephens anaesthetic machine. In
      study 1, the vaporizer setting, temperature and circuit FGFRs were altered with
      the vaporizer sleeve down (n = 3), or in separate experiments, up (n = 3).
      Delivered (Fi'SEVO) and expired sevoflurane concentrations were recorded. Study 2
      determined the vaporizer settings (sleeve up) required to achieve predetermined
      multiples of minimal alveolar concentration (MAC) of Fi'SEVO when sevoflurane was
      delivered to dogs (n = 12) of different bodyweights and at different FGFRs.
      RESULTS: Delivered concentrations of sevoflurane were sufficient to maintain
      anaesthesia in all dogs, regardless of bodyweight, FGFR, vaporizer temperature
      and sleeve position. Fi'SEVO increased with increasing temperature, when the
      vaporizer sleeve was down, when vaporizer setting was increased and when FGFR was
      decreased. As the FGFR increased or the dog's bodyweight decreased, higher
      vaporizer settings were required to produce the same Fi'SEVO. The median Stephens
      vaporizer settings to achieve an Fi'SEVO of 1.3 MAC ranged from 4.3 to 5.0 for a
      small dog (1-10 kg), 2.5 to 5.6 for a medium dog (15-25 kg) and 2.5 to 3.5 for a
      large dog (30-40 kg), depending on the FGFR. CONCLUSION AND CLINICAL RELEVANCE:
      The Stephens anaesthetic machine can deliver to dogs, weighing 4 kg and above,
      concentrations of sevoflurane sufficient or in excess of that required to
      maintain anaesthesia, at temperatures from 10 to 35  degrees C, FGFRs of 1 to 5
      times the patient's estimated metabolic oxygen requirement and at any vaporizer
      sleeve position.

PMID- 24020871
TI  - Immunohistochemical and FISH analysis of EGFR and its prognostic value in
      patients with oral squamous cell carcinoma.
AB  - OBJECTIVES: To study immunohistochemical expression of the epithelial growth
      factor receptor (EGFR) in oral carcinomas and the head and neck region to examine
      possible associations with various features of the tumors and survival of the
      patients. MATERIALS AND METHODS: Sections were made from two tissue arrays
      composed of 206 oral squamous cell carcinomas and 427 squamous cell carcinomas of
      the head and neck region, respectively, and examined for EGFR expression and Ki
      67 labeling index by means of immunohistochemistry, and for EGFR gene
      amplification by means of fluorescence in situ hybridization. Correlation between
      resulting parameters and with clinical features was evaluated using chi-square
      test and Kaplan-Meyer analysis. RESULTS: A statistically significant association
      was observed for strong EGFR immunohistochemical (IHC) expression with advanced
      lymph node involvement (P = 0.02). EGFR immunohistochemical expression did not
      significantly correlate with patient disease specific (DS) or overall survival
      (OS). EGFR gene amplification was not correlated with any of the tumor features
      nor to survival of the patients (DS and OS). DISCUSSION: Epithelial growth factor
      receptor IHC expression and gene amplification might be suitable to predict
      locoregional control in oral squamous cell carcinoma patients but an
      inappropriate predictor for patients survival.

PMID- 24020872
TI  - Measuring catch-up growth in malnourished populations.
AB  - BACKGROUND AND AIM: Numerous recent studies measure catch-up growth by regressing
      adult or pre-adolescent height on early childhood height. Using simple
      statistical theory and data from a healthy and well-nourished population, this
      paper shows that these tests are uninformative about the extent of catch-up
      growth. The study also provides new empirical evidence on pubertal catch-up
      growth using longitudinal data for rural Tanzania. SUBJECTS AND METHODS: The 1970
      British Cohort Study is used to demonstrate the flaws in the recent literature
      using regression techniques to study catch-up growth. The data for the empirical
      analysis come from the Kagera Health and Development survey-a longitudinal study
      spanning two decades. The final sample includes 540 children whose heights are
      measured in early childhood and in adulthood. Catch-up growth is measured as the
      change in height-for-age z-score over time. RESULTS: The mean HAZ-score in the
      cohort improves from -1.86 in early childhood to -1.20 in adulthood. Without
      catch-up growth, children would have been 4.5-5 centimetres shorter adults.
      Graphical analysis shows that most of this catch-up growth takes place in
      puberty. CONCLUSION: Catch-up growth after early childhood is possible. Puberty
      seems to offer an opportunity window for recovery.

PMID- 24020873
TI  - Is lower socioeconomic status associated with more advanced thyroid cancer stage
      at presentation? A study in two Canadian centers.
AB  - BACKGROUND: Some studies have shown a higher incidence of thyroid cancer in
      patients with insurance coverage and higher socioeconomic status (SES), and a
      higher thyroid cancer stage in patients with lower SES, suggesting SES-related
      health disparity in thyroid cancer. However, it is not known if the same is
      evident under a universal healthcare system such as that in Canada. METHODS: We
      used data from the Canadian Thyroid Cancer Consortium, a large thyroid cancer
      registry that collects data from two major thyroid cancer referral centers
      (London, Ontario, and Halifax, Nova Scotia). We included patients who presented
      with thyroid cancer between 1998 and 2011. We determined age at presentation,
      sex, and thyroid cancer status using the American Joint Committee on Cancer
      (AJCC) staging criteria. Individuals' postal codes were used to retrieve data
      from the Canadian census for the years 1996, 2001, and 2006 to approximate
      household income. Ordered logistic regression was used to determine odds ratios
      of presenting with more advanced stage thyroid cancer as they relate to income,
      age, and sex. RESULTS: We included 1701 patients: 1334 cases from London and 367
      from Halifax. Thyroid cancer was diagnosed more frequently in the higher SES
      groups (p<0.001). Compared to patients in the top income quintile, patients in
      the lowest and second-lowest income quintiles had significantly higher odds of
      having more advanced stage thyroid cancer at presentation (OR 1.58, p=0.002;
      1.37, p=0.024 respectively). CONCLUSIONS: Our study suggests that, similar to
      countries that lack a universal healthcare system, health disparity in thyroid
      cancer also exists in Canada. It appears that while thyroid cancers were
      diagnosed more frequently in Canadian patients of higher SES, Canadian patients
      in the lower SES groups had more advanced stage thyroid cancer at presentation.

PMID- 24020874
TI  - Toward a molecular theory of homogeneous bubble nucleation: I. Equilibrium embryo
      definition.
AB  - We propose an equilibrium embryo definition for homogeneous bubble nucleation
      within the pure component superheated Lennard-Jones liquid. The suggested embryo
      definition serves as an improvement to a previous (n,v) embryo model (Uline and
      Corti 2007). In that model, the constrained equilibrium between the bubble and
      the surrounding superheated liquid was maintained by placing n particles within a
      spherical volume v, without concern for the redundant counting of configurations
      and the relevance of the model to the dynamics of a nucleation process. To
      eliminate this redundancy, while only considering those embryos that should most
      likely appear at a transitional state, we now define the volume of the embryo via
      the use of a shell particle and only include n particles inside the volume that
      are deemed to be "vapor-like". The underlying free energy surface of formation of
      the new (n,v) embryo model is generated via Monte Carlo simulation and also
      approximately by a suggested density functional theory method. The resulting
      surface implies that small and locally confined regions of near-zero density
      serve as precursors initiating homogeneous bubble nucleation. Furthermore, the
      nonredundant counting of the embryo configurations yields a well-defined and
      sharp conduit in the free energy surface that directs the initially formed
      embryos toward the critical nucleus. We discuss how the suggested equilibrium
      embryo model aids in both the identification of the transitional configurations
      and calculation of the average number density of the critical nuclei within the
      superheated liquid phase, which is the focus of the companion paper (DOI
      10.1021/jp404151h).

PMID- 24020875
TI  - Stereotyped behaviours in children with autism spectrum disorders and atypical
      development as measured by the BPI-01.
AB  - OBJECTIVE: As repetitive behaviours in children with autism spectrum disorders
      (ASDs) can significantly interfere with one's daily functioning, continued
      research on these behaviours is needed. METHODS: This study examined the
      occurrence of repetitive motor movements in toddlers (17-37 months) with ASD and
      atypical development and the relationship between stereotypies and sensory
      impairment. RESULTS: Children with ASD (n = 13) exhibited significantly more
      repetitive behaviours than the non-ASD group (n = 12). Greater percentages of
      endorsement were evident for the ASD group on nearly all items of the Behaviour
      Problems Inventory-01 (BPI-01) Stereotypy subscale. More repetitive behaviours
      tended to co-occur with other stereotypies for the ASD group. A moderate
      correlation was found between stereotypy severity and sensory deficits.
      CONCLUSION: These findings suggest that stereotyped behaviours can be identified
      at very young ages, negatively affect the behavioural presentation of those with
      ASDs and should be considered when developing treatment plans.

PMID- 24020876
TI  - An analysis of the generalization and maintenance of eye contact taught during
      play.
AB  - PURPOSE: Differential reinforcement and most-to-least prompting were implemented
      within the context of developmentally appropriate play activities in an effort to
      improve the eye contact between a 4-year-old boy with pervasive developmental
      disorder-not otherwise specified (PDD-NOS) and his three therapists. METHODS: A
      multiple baseline design across therapists was used to examine the eye contact of
      a 4-year-old boy with PDD-NOS. Maintenance data were collected at 1, 2 and 3
      months post intervention. RESULTS: The intervention was effective and
      improvements in eye contact were maintained for at least 3 months post
      intervention. However, eye contact did not readily generalize across
      communication partners. CONCLUSIONS: Results suggest that eye contact may not
      generalize to communication partners who are not directly involved in
      intervention. Results are discussed in terms of implications for practitioners
      and directions for future research.

PMID- 24020877
TI  - A man with amyotrophic lateral sclerosis uses a mouth pressure microswitch to
      operate a text messaging system with a word prediction function.
AB  - OBJECTIVE: To assess whether a man with amyotrophic lateral sclerosis could
      benefit from using (a) a mouth pressure microswitch instead of an optic
      microswitch activated via head movement and (b) a special word prediction
      function within a text messaging system. METHOD: Initially, both microswitches
      were used for operating the text messaging system, and their effectiveness and
      the man's preference were assessed. Subsequently, only the mouth microswitch was
      used and the messaging system was provided with a word prediction function.
      RESULTS: The man was more efficient/rapid in using the text messaging (i.e., in
      writing) with the mouth microswitch and preferred such a microswitch. Similarly,
      he was more rapid in writing when the word prediction function was added (as
      opposed to the initial phase of the study when such function was not available)
      and preferred to use it. CONCLUSION: Technology updates are critical in helping
      persons with motor degeneration.

PMID- 24020878
TI  - Two men with multiple disabilities carry out an assembly work activity with the
      support of a technology system.
AB  - OBJECTIVE: To assess whether two persons with multiple disabilities could learn a
      work activity (i.e., assembling trolley wheels) with the support of a technology
      system. METHOD: After an initial baseline, the study compared the effects of
      intervention sessions relying on the technology system (which called the
      participants to the different workstations and provided feedback and final
      stimulation) with the effects of intervention sessions carried out without
      technology. The two types of intervention sessions were conducted according to an
      alternating treatments design. Eventually, only intervention sessions relying on
      the technology system were used. RESULTS: Both participants managed to assemble
      wheels independently during intervention sessions relying on the technology
      system while they failed during sessions without the system. Their performance
      was strengthened during the final part of the study, in which only sessions with
      the system occurred. CONCLUSION: Technology may be critical in helping persons
      with multiple disabilities manage multi-step work activities.

PMID- 24020879
TI  - Towards improved ways of knowing children with profound multiple disabilities:
      introducing startle reflex modulation.
AB  - OBJECTIVE: To propose startle reflex modulation (SRM) as an objective measure of
      emotions of children with profound multiple disabilities (PMD). Knowledge about
      emotion states of children with PMD is crucial to their individualised care and
      support. Proxy reporting, observational and physiological measures of emotion are
      reported in the literature. Despite advances in this science, the rigour of the
      findings and methods are contested. In this article, we introduce SRM; a
      neurophysiological measure untried with children with PMD, despite its well-known
      sensitivity to even subtle changes in affective processing without depending on
      explicit responses. RESULTS: We propose a research agenda that aims to deliver a
      more comprehensive and accurate profile of the inner states of these children,
      based upon previous research undertaken using SRM. CONCLUSION: It is suggested
      that this objective measure has potential to provide useful information about the
      inner emotional states of children with PMD.

PMID- 24020881
TI  - Effect of hydrogen bond formation on the NMR properties of glycine-HCN complexes.
AB  - The influence of the hydrogen bond formation on the nuclear magnetic resonance
      parameters has been investigated for the binary (1:1) and ternary (1:2) glycine
      HCN complexes in the gas phase using high-level density functional theory with
      the B3LYP/6-31++G(2d,2p)//B3LYP/6-31++G(d,p) model of quantum chemistry. The
      calculated isotropic/anisotropic shielding parameters of the isolated glycine and
      HCN molecules are reported and compared with other theoretical results and
      experimental measurements. Six different conformations of hydrogen-bonded
      clusters have considered for both 1:1 and 1:2 glycine-HCN complexes. The
      isotropic and anisotropic chemical shifts for all the constituent atoms of the
      complexes have been calculated. The spin-spin coupling constants and the Fermi
      contact terms have also been analyzed in the context of hydrogen-bond formation. 

PMID- 24020880
TI  - Enhanced primers for amplification of DNA barcodes from a broad range of marine
      metazoans.
AB  - BACKGROUND: Building reference libraries of DNA barcodes is relatively
      straightforward when specifically designed primers are available to amplify the
      COI-5P region from a relatively narrow taxonomic group (e.g. single class or
      single order). DNA barcoding marine communities have been comparatively harder to
      accomplish due to the broad taxonomic diversity and lack of consistently
      efficient primers. Although some of the so-called "universal" primers have been
      relatively successful, they still fail to amplify COI-5P of many marine animal
      groups, while displaying random success even among species within each group.
      Here we propose a new pair of primers designed to enhance amplification of the
      COI-5P region in a wide range of marine organisms. RESULTS: Amplification tests
      conducted on a wide range of marine animal taxa, rendered possible the first-time
      sequencing of DNA barcodes from eight separated phyla (Annelida, Arthropoda,
      Chordata, Cnidaria, Echinodermata, Mollusca, Nemertea and Platyhelminthes),
      comprising a total of 14 classes, 28 orders, 57 families, 68 genus and 76
      species. CONCLUSIONS: These primers demonstrated to be highly cost-effective,
      which is of key importance for DNA barcoding procedures, such as for building
      comprehensive DNA barcode libraries of marine communities, where the processing
      of a large numbers of specimens from a wide variety of marine taxa is compulsory.

PMID- 24020882
TI  - Statins, percutaneous coronary intervention and myocardial infarction.
AB  - Peri-procedural myocardial infarction occurs in up to 40% of otherwise successful
      percutaneous coronary intervention (PCI) procedures and such patients have a
      worse long term prognosis than those who do not have this complication. Statins
      administered at the time of PCI, particularly before the procedure, have been
      shown to reduce the risk of myocardial infarction during PCI, but the
      applicability of this treatment may be limited because of the widespread use of
      statins in patients with existing coronary artery disease, or in those at risk of
      developing the disease. The results of a study are reported in this issue of the
      journal in which a single dose of atorvastatin is given prior to PCI to patients
      already taking a statin, and shows a significant reduction in the risk of peri
      procedural myocardial infarction. It may be that a single supplemental dose of a
      statin at PCI to all patients could confer clinical benefit.

PMID- 24020883
TI  - Electrochemical detection of dual exposure biomarkers of organophosphorus agents
      based on reactivation of inhibited cholinesterase.
AB  - Considering inter- or intra-individual variation in the normal levels of
      acetylcholinesterase (AChE), real-time measurement of AChE via the reactivation
      from a postexposure sample was used, and thus a baseline-free and reliable
      approach was proposed for detecting/screening low-dose organophosphorus
      pesticides (OPs) poisons. The principle of this technology is on the basis of
      parallel measurements of AChE activity before and after reactivation from a
      postexposure to simultaneously provide the content of dual biomarkers of both
      enzyme inhibition and enzyme adducts. It is more accurate and reliable compared
      with only one biomarker (inhibition or adduct). Reactivation from a postexposure
      sample is a better individual enzyme baseline compared to pre-exposure from the
      population average level in currently available approaches. AChE activity was
      measured with an electrochemical method. Greatly enhanced sensitivity was
      achieved by using Fe3O4/Au nanocomposites to enrich thiocholine, the hydrolysis
      product of active AChE, followed by electrochemical oxidative desorption of the
      adsorbed thiocholine. The validation of this method for measurement of OP
      exposures was further explored with in vitro paraoxon inhibited human red blood
      cells (RBCs) samples and demonstrated its practicability. 

PMID- 24020884
TI  - Written informed consent for living kidney donors: practices and compliance with
      CMS and OPTN requirements.
AB  - We sought to assess how written informed consent practices for candidate living
      kidney donors have changed over the last 5 years and to assess compliance with
      Centers for Medicare and Medicaid (CMS) and Organ Procurement and Transplantation
      Network (OPTN) regulations that took effect in 2007. We requested evaluation
      consent forms from US centers that performed >5 living kidney transplants during
      the prior year (n = 184). We received 148 consent forms; each was reviewed for
      information provided and inclusion of CMS- and OPTN-required elements. We found
      that nearly all transplant centers now obtain written consent for living kidney
      donor evaluation. However, most centers' evaluation consent forms do not include
      all CMS and OPTN requirements. Multiple items balancing donor and recipient
      interests and confidentiality were omitted. In addition, information about
      payment for routine follow-up care, complications related to surgery and other
      health problems following surgery were highly variable and frequently ambiguous.
      As centers revise their consent forms to address the 2013 OPTN policies, our
      findings may help them identify areas of potential deficiency. We propose that
      UNOS develop a uniform donor evaluation consent form to improve the clarity,
      consistency and efficiency of living donor consent.

PMID- 24020885
TI  - Getting psychosocial interventions into mental health nursing practice: a survey
      of skill use and perceived benefits to service users.
AB  - AIM: To investigate the use of psychosocial interventions by mental health nurses
      following training and perceived benefits to service users. BACKGROUND:
      Psychosocial interventions are recommended to support the recovery of persons
      with enduring mental illness. Despite two decades of postgraduate training in
      psychosocial interventions internationally, implementation challenges still
      remain. DESIGN: A cross-sectional exploratory, descriptive survey was employed.
      METHODS: A survey was mailed to the total population of nurses (n = 58) working
      in some health regions in Ireland who completed training in psychosocial
      interventions between 2005-2010. Data were collected between November 2011
      January 2012, yielding a response rate of 64%. Descriptive and correlational
      statistics were used to analyse the data. RESULTS: There were statistically
      significant increases in the use of psychosocial interventions post training.
      Cognitive behavioural therapy and family interventions were the least used
      interventions. Assessment and outcome measures, concordance therapy and relapse
      prevention were preferential interventions. Perceived outcomes for service users
      were awareness of relapse indicators, enhanced coping skills and fewer
      admissions. Case load demands, lack of access to supervision and time constraints
      prevented implementation. Free text comments indicated a dissonance between
      generic nursing roles and implementation of structured psychosocial interventions
      in practice. CONCLUSIONS: The findings indicate a requirement for nursing
      leadership to legitimize psychosocial interventions as core nursing work. For
      service users to experience this type of nursing, we propose the nomination of
      dedicated psychosocial intervention nurses to multidisciplinary teams. Support
      through guidelines, clinical supervision and audit by senior nurse managers is
      critical to implementation.

PMID- 24020886
TI  - Host cell contact induces fur-dependent expression of virulence factors CagA and
      VacA in Helicobacter pylori.
AB  - BACKGROUND: Helicobacter pylori, a gram negative bacterium, colonizes the stomach
      in a majority of the world population. The two major virulence factors of H.
      pylori VacA and CagA, thought to be associated with chronic inflammation and
      disease, have been extensively studied, but the regulation of the expression of
      these virulence genes in H. pylori remains poorly understood. METHODS: qRT-PCR
      was performed to quantify gene expression in unadhered and AGS-adhered H. pylori.
      Deltafur mutant was constructed by splicing by overlap extension PCR and allelic
      exchange. RESULTS: Adherence of H. pylori to the gastric epithelial cell line AGS
      strongly induces the expression of both cagA and vacA. Induction of cagA and vacA
      in the AGS cell-adhered H. pylori Deltafur mutant strain was consistently lower
      than in the adhered parent strain. However, expression of the genes was similar
      between the wild-type and Deltafur mutant strains in the unadhered state,
      suggesting that Fur has a role in the upregulation of cagA and vacA expression,
      especially in AGS-adhered H. pylori. Consistent with these results, microscopic
      observations revealed that infection of AGS cells with H. pylori Deltafur mutant
      strain produced much less damage as compared to that produced by the wild-type H.
      pylori strain. CONCLUSIONS: These results suggested that cagA and vacA gene
      expression is upregulated in H. pylori, especially by host cell contact, and Fur
      has a role in the upregulation.

PMID- 24020887
TI  - Engineering E. coli strain for conversion of short chain fatty acids to
      bioalcohols.
AB  - BACKGROUND: Recent progress in production of various biofuel precursors and
      molecules, such as fatty acids, alcohols and alka(e)nes, is a significant step
      forward for replacing the fossil fuels with renewable fuels. A two-step process,
      where fatty acids from sugars are produced in the first step and then converted
      to corresponding biofuel molecules in the second step, seems more viable and
      attractive at this stage. We have engineered an Escherichia coli strain to take
      care of the second step for converting short chain fatty acids into corresponding
      alcohols by using butyrate kinase (Buk), phosphotransbutyrylase (Ptb) and
      aldehyde/alcohol dehydrogenase (AdhE2) from Clostridium acetobutylicum. RESULTS:
      The engineered E. coli was able to convert butyric acid and other short chain
      fatty acids of chain length C3 to C7 into corresponding alcohols and the
      efficiency of conversion varied with different E. coli strain type. Glycerol
      proved to be a better donor of ATP and electron as compared to glucose for
      converting butyric acid to butanol. The engineered E. coli was able to tolerate
      up to 100 mM butyric acid and produced butanol with the conversion rate close to
      100% under anaerobic condition. Deletion of native genes, such as fumarate
      reductase (frdA) and alcohol dehydrogenase (adhE), responsible for side products
      succinate and ethanol, which act as electron sink and could compete with butyric
      acid uptake, did not improve the butanol production efficiency. Indigenous acyl
      CoA synthetase (fadD) was found to play no role in the conversion of butyric acid
      to butanol. Engineered E. coli was cultivated in a bioreactor under controlled
      condition where 60 mM butanol was produced within 24 h of cultivation. A
      continuous bioreactor with the provision of cell recycling allowed the continuous
      production of butanol at the average productivity of 7.6 mmol/l/h until 240 h.
      CONCLUSIONS: E. coli engineered with the pathway from C. acetobutylicum could
      efficiently convert butyric acid to butanol. Other short chain fatty acids with
      the chain length of C3 to C7 were also converted to the corresponding alcohols.
      The ability of engineered strain to convert butyric acid to butanol continuously
      demonstrates commercial significance of the system.

PMID- 24020889
TI  - Lexical and phrasal prominence patterns in school-aged children's speech.
AB  - This study investigated the integration of word- and phrase-level prominences in
      speech produced by twenty-five school-aged children (6;2 to 7;3) and twenty-five
      adults. Participants produced disyllabic number words in a straight count
      condition and in two phrasal conditions, namely, a stress clash and non-clash
      phrasal context. Duration and amplitude measures of syllable rhymes were used to
      assess the realization of lexical stress, and fundamental frequency (F0) measures
      were used to assess the realization of phrasal pitch accents across conditions.
      Results showed that the duration and F0 correlates varied independently of each
      other as a function of condition in child speech, but much less so in adult
      speech. The group differences were taken to indicate that six-year-old children
      have yet to develop prosodic structures with integrated prominence. Structural
      and pragmatic interpretations of the results are discussed.

PMID- 24020890
TI  - Pharmacokinetic study in pigs and in vitro metabolic characterization in pig- and
      human-liver microsomes reveal marked differences in disposition and metabolism of
      tiletamine and zolazepam (Telazol).
AB  - 1. An equal-dose combination of tiletamine and zolazepam (Telazol(r)) is used as
      a veterinary anesthetic. There also have been reports of human abuse of
      Telazol(r). The pharmacokinetics and metabolic fate of tiletamine and zolazepam
      and the rationale for their administration as an equal-dose combination are
      unclear. 2. The single-dose pharmacokinetics of intramuscular tiletamine and
      zolazepam (3 mg/kg each) in 16 Yorkshire-crossbred pigs were determined. The
      metabolites of tiletamine and zolazepam in pig plasma and urine were identified
      by mass spectrometry. The metabolic stability of tiletamine and zolazepam and the
      kinetics of formation of their metabolites by pig- and human-liver microsomes
      were determined. 3. Higher concentrations of zolazepam were observed in pig
      plasma and it was cleared more slowly compared to tiletamine (apparent clearance:
      11 versus 134 l/h; half-life: 2.76 versus 1.97 h). Three metabolites of zolazepam
      and one metabolite of tiletamine were identified in pig urine, plasma and in
      microsomal incubations. In vitro formation of each of these metabolites in
      microsomes was biphasic involving a high-affinity/low-capacity and a low
      affinity/high-capacity enzyme. The in vitro metabolic stability of tiletamine was
      considerably lower compared to zolazepam. 4. These results collectively point to
      major pharmacokinetic and metabolic differences between the two components of
      this fixed-dose anesthetic combination.

PMID- 24020888
TI  - Rate-dependent Ca2+ signalling underlying the force-frequency response in rat
      ventricular myocytes: a coupled electromechanical modeling study.
AB  - BACKGROUND: Rate-dependent effects on the Ca2+ sub-system in a rat ventricular
      myocyte are investigated. Here, we employ a deterministic mathematical model
      describing various Ca2+ signalling pathways under voltage clamp (VC) conditions,
      to better understand the important role of calmodulin (CaM) in modulating the key
      control variables Ca2+/calmodulin-dependent protein kinase-II (CaMKII),
      calcineurin (CaN), and cyclic adenosine monophosphate (cAMP) as they affect
      various intracellular targets. In particular, we study the frequency dependence
      of the peak force generated by the myofilaments, the force-frequency response
      (FFR). METHODS: Our cell model incorporates frequency-dependent CaM-mediated
      spatially heterogenous interaction of CaMKII and CaN with their principal targets
      (dihydropyridine (DHPR) and ryanodine (RyR) receptors and the SERCA pump). It
      also accounts for the rate-dependent effects of phospholamban (PLB) on the SERCA
      pump; the rate-dependent role of cAMP in up-regulation of the L-type Ca2+ channel
      (ICa,L); and the enhancement in SERCA pump activity via phosphorylation of PLB.
      RESULTS: Our model reproduces positive peak FFR observed in rat ventricular
      myocytes during voltage-clamp studies both in the presence/absence of cAMP
      mediated beta-adrenergic stimulation. This study provides quantitative insight
      into the rate-dependence of Ca2+-induced Ca2+-release (CICR) by investigating the
      frequency-dependence of the trigger current (ICa,L) and RyR-release. It also
      highlights the relative role of the sodium-calcium exchanger (NCX) and the SERCA
      pump at higher frequencies, as well as the rate-dependence of sarcoplasmic
      reticulum (SR) Ca2+ content. A rigorous Ca2+ balance imposed on our investigation
      of these Ca2+ signalling pathways clarifies their individual roles. Here, we
      present a coupled electromechanical study emphasizing the rate-dependence of
      isometric force developed and also investigate the temperature-dependence of FFR.
      CONCLUSIONS: Our model provides mechanistic biophysically based explanations for
      the rate-dependence of CICR, generating useful and testable hypotheses. Although
      rat ventricular myocytes exhibit a positive peak FFR in the presence/absence of
      beta-adrenergic stimulation, they show a characteristic increase in the positive
      slope in FFR due to the presence of Norepinephrine or Isoproterenol. Our study
      identifies cAMP-mediated stimulation, and rate-dependent CaMKII-mediated up
      regulation of ICa,L as the key mechanisms underlying the aforementioned positive
      FFR.

PMID- 24020891
TI  - Postoperative hyperopic shift after cataract surgery in silicone oil-filled eyes.

PMID- 24020892
TI  - Screening for thyroid dysfunction during the second trimester of pregnancy.
AB  - The primary objective of this study is to explore the influence of different
      screening strategies on the prevalence of thyroid dysfunction and the missed
      diagnosis during pregnancy. A total of 1889 pregnant women (13-27 weeks) were
      divided into high-risk and low-risk groups according to the backgrounds of them
      collected by questionnaire. We detected the prevalence of thyroid dysfunction in
      high-risk groups and low-risk pregnant women by normal reference range during the
      second trimester in our research. High-risk groups accounted for 10.69% of all
      the pregnant women in this study. Using targeted high-risk case screening
      strategy, misdiagnosis rate of pregnancy with hyperthyroidism, subclinical
      hyperthyroidism, pregnancy with hypothyroidism, subclinical hypothyroidism, low
      T4 syndrome and positive TPOAb were 87.5% (14 cases), 87.08% (155 cases), 87.08%
      (155 cases), 83.93% (47 cases), 89.47% (17 cases) and 88.35% (91 cases),
      respectively. Furthermore, there was no statistically significant difference
      between high-risk group and low-risk group in the prevalence of thyroid
      dysfunction. Therefore, we believe that universal screening to pregnant women can
      effectively reduce misdiagnosis rate of thyroid dysfunction. Further, we
      recommend universal screening for thyroid function in second trimester of
      pregnancy.

PMID- 24020893
TI  - Kidney function and clinical recommendations of drug dose adjustment in geriatric
      patients.
AB  - BACKGROUND: In elderly patients chronic kidney disease often limits drug
      prescription. As several equations for quick assessment of kidney function by
      estimating glomerular filtration rate (eGFR) and several different clinical
      recommendations for drug dose adjustment in renal failure are published, choosing
      the correct approach for drug dosage is difficult for the practitioner. The aims
      of our study were to quantify the agreement between eGFR-equations grouped by
      creatinine-based or cystatin C-based and within the groups of creatinine and
      cystatin C-based equations and to investigate whether use of various literature
      and online references results in different recommendations for drug dose
      adjustment in renal disease in very elderly primary care patients. METHODS: We
      included 108 primary care patients aged 80 years and older from 11 family
      practices into a cross-sectional study. GFR was estimated using two serum
      creatinine-based equations (Cockroft-Gault, MDRD) and three serum cystatin C
      based equations (Grubb, Hoek, Perkins). Concordance between different equations
      was quantified using intraclass correlation coefficients (ICCs). Essential
      changes in drug doses or discontinuation of medication were documented and
      compared in terms of estimated renal function as a consequence of the different
      eGFR-equations using five references commonly used in the US, Great Britain and
      Germany. RESULTS: In general, creatinine-based equations resulted in lower eGFR
      estimation and in higher necessity of drug dose adjustment than cystatin C-based
      equations. Concordance was high between creatinine-based equations alone (ICCs
      0.87) and between cystatin C-based equations alone (ICCs 0.90 to 0.96), and
      moderate between creatinine-based equations and cystatin C-based equations (ICCs
      0.54 to 0.76). When comparing the five different references consulted to identify
      necessary drug dose adjustments we found that the numbers of drugs that
      necessitate dose adjustment in the case of renal impairment differed
      considerably. The mean number of recommended changes in drug dosage ranged
      between 1.9 and 2.5 per patient depending on the chosen literature reference.
      CONCLUSIONS: Our data suggest that the choice of the literature source might have
      even greater impact on drug management than the choice of the equation used to
      estimate GFR alone. Efforts should be deployed to standardize methods for
      estimating kidney function in geriatric patients and literature recommendations
      on drug dose adjustment in renal failure.

PMID- 24020894
TI  - Decreasing incidence of AA amyloidosis in Spain.

PMID- 24020895
TI  - What do we know about tocolytic effectiveness and how do we use this information
      in guidelines? A comparison of evidence grading.
AB  - BACKGROUND: Evidence summaries of tocolytic effectiveness assign quality levels
      based on a single dimension: the study design. The Grading of Recommendations
      Assessment, Development and Evaluation (GRADE) system takes into account several
      domains, including limitations of the study design and ranking the importance of
      outcomes. OBJECTIVES: The aim of the study was to compare the quality of evidence
      according to GRADE with the quality as described by existing guidelines. SEARCH
      STRATEGY: A practitioner survey to rank the importance of outcomes and a
      systematic review were conducted. For the systematic review, we searched Medline,
      Embase, and DARE databases from inception to December 2010 using the terms
      'tocolytics' and 'threatened preterm labour', without any language restrictions.
      SELECTION CRITERIA: Inclusion criteria for the review were randomised controlled
      trials comparing tocolytics with either placebo or betamimetics. DATA COLLECTION
      AND ANALYSIS: The review and survey teams worked independently. Evidence ratings
      according to GRADE were performed. MAIN RESULTS: The majority of the survey
      respondents thought that it was important to use tocolytics to buy the time
      needed for steroids to promote fetal lung maturation and to allow in utero
      transfer. Nearly 80% of 'high' ratings in guidelines were downgraded as a result
      of deficiencies identified by GRADE. AUTHORS' CONCLUSIONS: We propose a move away
      from the use of evidence rating systems reliant solely on study design, as they
      have a propensity towards strong recommendations when the underlying evidence is
      weak.

PMID- 24020900
TI  - Genetic architecture of HIV type 1 Nef and Tat from HLA-B57-typed long-term
      survivors in an Indian cohort of perinatally HIV-infected children.
AB  - Human immunodeficiency virus type 1 (HIV-1) viral genes nef and tat play an
      important role in disease progression. In this study we characterized the Nef and
      Tat proteins from a group of HLA-B57 typed pediatric perinatally infected long
      term survivors (LTS) with >=10 years of infection. We identified 19 therapy-naive
      LTS after screening 250 children from an Indian pediatric cohort. Nef and tat
      amplified from plasma virus showed that all the LTS harbored HIV-1 subtype C. The
      two B57(+) children showed mutations, deletions, and insertions in experimentally
      defined B57 epitopes in the virus that are likely to be escape mutants. Only GW12
      (GPGVRYPLTFGW) and YY9 (YTPGPGIRY) were conserved, while the remaining 90%
      (18/20) of the epitopes showed some degree of mutations. The most variable
      epitopes were RR15, SE15, QP15, KF9, HW9, YT9, and GF15. To our knowledge this is
      the first study from India in which characterization of Nef and Tat from LTS has
      led to information on genetic alterations in these genes that are associated with
      slow disease progression, and can provide an important lead in future studies.

PMID- 24020901
TI  - Toward a molecular theory of homogeneous bubble nucleation: II. Calculation of
      the number density of critical nuclei and the rate of nucleation.
AB  - In the present paper, we develop a method to calculate the rate of homogeneous
      bubble nucleation within a superheated L-J liquid based on the (n,v) equilibrium
      embryo free energy surface introduced in the first paper (DOI:
      10.1021/jp404149n). We express the nucleation rate as the product of the
      concentration of critical nuclei within the metastable liquid phase and the
      relevant forward rate coefficient. We calculate the forward rate coefficient of
      the critical nuclei from their average lifetime as determined from MD simulations
      of a large number of embryo trajectories initiated from the transitional region
      of the metastable liquid configuration space. Therefore, the proposed rate
      coefficient does not rely on any predefined reaction coordinate. In our model,
      the critical nuclei belong to the region of the configuration space where the
      committor probability is about one-half, guaranteeing the dynamical relevance of
      the proposed embryos. One novel characteristic of our approach is that we define
      a limit for the configuration space of the equilibrium metastable phase and do
      not include the configurations that have zero committor probability in the
      nucleation free energy surface. Furthermore, in order to take into account the
      transitional degrees of freedom of the critical nuclei, we develop a simulation
      based approach for rigorously mapping the free energy of the (n,v) equilibrium
      embryos to the concentration of the critical nuclei within the bulk metastable
      liquid phase.

PMID- 24020899
TI  - Peroxisome proliferator-activated receptor gamma agonist effect on rheumatoid
      arthritis: a randomized controlled trial.
AB  - INTRODUCTION: Rheumatoid arthritis (RA), a chronic inflammatory disease, is
      associated with insulin resistance. Experimental evidence indicates that the
      relationship between insulin resistance and inflammation is bidirectional:
      Inflammation promotes insulin resistance, and insulin resistance promotes
      inflammation. Therefore, we examined the hypothesis that pioglitazone, a
      thiazolidinedione peroxisome proliferator-activated receptor gamma agonist, would
      decrease inflammation and disease activity and improve insulin resistance in
      patients with RA. METHODS: In a single-center, randomized, double-blind, placebo
      controlled crossover study patients with RA (N = 34) receiving stable therapy
      were randomized to also receive either pioglitazone 45 mg daily (n = 17) or
      matching placebo (n = 17) for eight weeks. This was followed by a four-week
      washout period and alternative treatment for eight weeks. Outcomes included
      change in Disease Activity Score in 28 joints (DAS28) score, individual
      components of the DAS28 score and homeostatic model assessment for insulin
      resistance (HOMA). Intention-to-treat analysis and linear mixed-effects models
      were used. RESULTS: Patients had a mean (+/- SD) age of 51 (+/- 14.2) years,
      82.4% were female and baseline DAS28 high-sensitivity C-reactive protein (DAS28
      CRP) was 4.58 (+/- 1.1) units. Addition of pioglitazone was associated with a
      9.3% reduction (95% confidence interval (CI) = 0.17% to 17.6%) in DAS28-CRP (P =
      0.046), but no significant change in DAS28 erythrocyte sedimentation rate (DAS28
      ESR) (P = 0.92). There was a 10.7 mm (95% CI = 0.4 to 20.9 mm) improvement in
      patient-reported global health (P = 0.042), a 48.6% decrease (95% CI = 27.6% to
      63.5%) in CRP (P < 0.001) and a 26.4% decrease (95% CI = 3.7% to 43.8%) in
      insulin resistance as measured by HOMA (P = 0.025), but no significant reduction
      in swollen or tender joint count or in ESR (all P > 0.05). Lower-extremity edema
      was more common during pioglitazone treatment (16%) than placebo (0%).
      CONCLUSION: Addition of pioglitazone to RA therapy improves insulin resistance
      and modestly reduces RA disease activity measured by DAS28-CRP and two of its
      components, including patient-reported global health and CRP, but not DAS28-ESR
      or ESR. TRIAL REGISTRATION: NCT00763139.

PMID- 24020902
TI  - Rippling graphene at the nanoscale through dislocation addition.
AB  - Ripples in graphene are an out-of-plane distortion that help stabilize suspended
      monolayer graphene. The introduction of disclinations and dislocations into the
      lattice of graphene is predicted to extensively ripple graphene to form
      "hillocks" to accommodate the strain in the system. Here, we confirm this
      theoretical prediction by intentionally introducing large numbers of dislocations
      into a predefined area of pristine monolayer graphene by scanning focused
      electron beam irradiation and imaging the rippled atomic lattice structure with
      aberration-corrected transmission electron microscopy. Hillocks are observed and
      analyzed using geometric phase analysis to determine heights of ~0.5 nm. Time
      dependent imaging shows the rippling is dynamic under the electron beam and can
      fluctuate between different structural configurations. This demonstrates a means
      of perturbing the structure of graphene in all three spatial dimensions with
      nanoscale precision.

PMID- 24020903
TI  - Relationship between microRNA expression levels and histopathological features of
      dysplasia in oral leukoplakia.
AB  - BACKGROUND: Increased expression of microRNAs (miRNAs), miR-21, miR-345, and miR
      181b has been demonstrated in oral leukoplakia (OL) that progresses to oral
      squamous cell carcinoma (OSCC), suggesting a miRNA signature with potential
      prognostic value. On the basis of these findings, this pilot study aimed to
      investigate the cytological and histopathological features that are used to grade
      oral dysplasia and determine associations with the expression of these 3
      potentially cancer-related miRNAs. We also compared the expression levels of
      these miRNAs in OL with normal oral mucosa and OSCC. METHODS: We evaluated miRNA
      expression by qPCR in 22 samples of OL demonstrating different grades of
      dysplasia, as well as 17 cases of OSCC, and 6 samples of normal oral mucosa. We
      associated the miRNAs expression profiles with cytological and histopathological
      features of OL. RESULTS: OSCC cases showed increased expression of all 3 miRNAs
      when compared with OL and normal oral mucosa. Increased expression of miR-21 was
      also observed in OL when compared with normal oral mucosa. We found a higher
      expression of miR-21 and miR-181b in OL that presented with an increased number
      of mitotic figures, increased nuclear/cytoplasmic ratio, or hyperchromasia.
      Increased expression of miR-21 was also detected in OL with abnormally
      superficial mitosis. Higher expression of miR-345 was observed in OL with an
      increased number and size of nucleoli or increased nuclear/cytoplasmic ratio.
      CONCLUSIONS: In conclusion, the present study shows that some cytological and
      histopathological parameters used to grade dysplasia are associated with altered
      miRNA expression.

PMID- 24020904
TI  - Leaf microbiota of strawberries as affected by biological control agents.
AB  - The increasing use of biological control agents (BCAs) against Botrytis cinerea
      in strawberry raises the question of whether there are any undesirable impacts of
      foliar applications of BCAs on nontarget microorganisms in the phyllosphere.
      Therefore, our objective was to investigate this issue within a field study.
      Strawberry plants were repeatedly sprayed with three BCAs-namely, RhizoVital 42
      fl. (Bacillus amyloliquefaciens FZB42), Trianum-P (Trichoderma harzianum T22),
      and Naturalis (Beauveria bassiana ATCC 74040)-to suppress Botrytis cinerea
      infections. Microbial communities of differentially treated leaves were analyzed
      using plate counts and pyrosequencing and compared with the microbial community
      of nontreated leaves. Plate count results indicate that the applied Bacillus and
      Trichoderma spp. survived in the strawberry phyllosphere throughout the
      strawberry season. However, no significant impacts on the leaf microbiota could
      be detected by this culture-dependent technique. Pyrosequencing of internal
      transcribed spacer ribosomal RNA and 16S RNA sequences revealed a change in
      fungal composition and diversity at class level after the introduction of T.
      harzianum T22 to the phyllosphere, whereas the bacterial composition and
      diversity was not affected by either this Trichoderma preparation or the other
      two BCAs. Our results suggest that pyrosequencing represents a useful method for
      studying microbial interactions in the phyllosphere.

PMID- 24020905
TI  - Living kidney donor assessment: challenges, uncertainties and controversies among
      transplant nephrologists and surgeons.
AB  - The assessment of living kidney donors presents unique ethical challenges and
      complex psychosocial implications. This study aimed to ascertain the perspectives
      of transplant nephrologists and surgeons on living kidney donor assessment. Semi
      structured, face-to-face interviews were conducted with 110 transplant
      nephrologists and surgeons from 43 transplant units in 12 countries from Europe,
      Australasia and North America. The challenge of defining acceptable risk to the
      donor was central to five themes identified: burden of responsibility (personal
      accountability, policing morality, democratic decision making, meeting legal
      obligations, optimizing outcomes and innovation, relinquished control); medical
      protectiveness (prognostic uncertainty, skepticism of donor risk perception,
      avoidance of undue coercion, concerns for dubious motivations and coercion,
      safeguard donor well-being, ethical information disclosure); respecting donor
      autonomy (facilitate informed-decision making, concede to donor risk acceptance,
      benefit of the doubt, donor mandate to maintain health, acceptable altruism);
      driving ideologies (preserving equity, championing living donation, cognizance of
      anti-paternalism) and contextual pressures (evolving donor demographic, resource
      limitations). Living kidney donor assessment involves complex interactions
      between safeguarding the donors' welfare and respecting their autonomy. In our
      opinion, authoritative and well-described transplant unit, hospital and public
      policy positions that make explicit the considerations that are often implicit
      may reduce the uncertainty within which living donors are assessed today. 

PMID- 24020906
TI  - Reprogramming microbes to be pathogen-seeking killers.
AB  - Recent examples of new genetic circuits that enable cells to acquire biosynthetic
      capabilities, such as specific pathogen killing, present an attractive
      therapeutic application of synthetic biology. Herein, we demonstrate a novel
      genetic circuit that reprograms Escherichia coli to specifically recognize,
      migrate toward, and eradicate both dispersed and biofilm-encased pathogenic
      Pseudomonas aeruginosa cells. The reprogrammed E. coli degraded the mature
      biofilm matrix and killed the latent cells encapsulated within by expressing and
      secreting the antimicrobial peptide microcin S and the nuclease DNaseI upon the
      detection of quorum sensing molecules naturally secreted by P. aeruginosa.
      Furthermore, the reprogrammed E. coli exhibited directed motility toward the
      pathogen through regulated expression of CheZ in response to the quorum sensing
      molecules. By integrating the pathogen-directed motility with the dual
      antimicrobial activity in E. coli, we achieved signifincantly improved killing
      activity against planktonic and mature biofilm cells due to target localization,
      thus creating an active pathogen seeking killer E. coli. 

PMID- 24020907
TI  - Sustainability: an evolutionary concept analysis. Exploring nursing's role within
      the sustainability movement.
AB  - AIM: This paper aimed to explore the evolution of the concept of sustainability
      to facilitate further knowledge development in the discipline of nursing.
      BACKGROUND: The concept of 'sustainability' emerged in the 1950s as a result of
      the environmental movement. The concept has been adapted by the discipline of
      management and is increasingly discussed in the context of health care. The
      concept remains ambiguous in the discipline of nursing, resulting in a struggle
      to articulate the role of nursing in the sustainability movement. DESIGN: Rodgers
      evolutionary method of concept analysis was used. DATA SOURCES: Literature was
      searched from 1987-2011, including English, peer reviewed texts in the databases
      CINAHL and ABI/INFORM global. Two book chapters and grey literature were also
      included. REVIEW METHODS: References were read and analysed according to
      antecedents, attributes, consequences, surrogate terms and related terms.
      RESULTS: Defining antecedents, attributes and consequences highlight the
      complexity and diversity of the concept. Attributes include: sustainability as a
      condition of change, as process, as outcome, as dependent of multiple
      stakeholders, and as social consciousness. 'Sustainability' is a fragile concept
      highly dependent on the processes and stakeholders involved in its fruition.
      There is a distinct difference in the level of concept clarity between the
      disciplines of management and nursing. CONCLUSIONS: The complexities associated
      with the concept of 'Sustainability' have led to its ambiguity. Nursing must,
      however, work to further clarify the concept to fully understand nursing's
      potential role in the sustainability movement.

PMID- 24020908
TI  - Longitudinal evaluation of endothelial function in children and adolescents with
      type 1 diabetes mellitus: a long-term follow-up study.
AB  - BACKGROUND: Type 1 diabetes (T1DM) predisposes to cardiovascular disease,
      increasing the risk to develop atherosclerosis. In the pediatric population, the
      cardiovascular risk may be evaluated examining endothelial function by a non
      invasive ultrasound technique, namely flow-mediated dilation (FMD) of the
      brachial artery. The aims of this study were the longitudinal evaluation of the
      potential change in the endothelium-dependent vasomotor function in children and
      adolescents with T1DM and the identification of clinical and laboratory data
      correlated to modifications. METHODS: We studied 39 T1DM patients (20 girls and
      19 boys; aged 11.2 +/- 3.72 years). FMD and blood samples were obtained from all
      patients at baseline (time 0) and after a follow up of at least 1 year (time 1).
      FMD was also evaluated in 45 healthy controls (22 boys, 23 girls) aged 10.2 +/-
      3.05 years. RESULTS: At time 0, 43.6% of T1DM patients presented an impaired FMD.
      FMD at time 1 revealed a dramatic impairment of endothelial function: altered FMD
      values were shown in 61.5% of patients and it got worse in 74.3% of them.
      Longitudinally, boys had a greater impairment of FMD than girls. At baseline,
      multivariate analysis identified only sex as significant predictor of FMD (beta =
      0.470, P = 0.029). CONCLUSIONS: Because endothelial dysfunction appears earlier
      in diabetic children, they are at higher risk to develop atherosclerosis. Our
      results suggest the usefulness of FMD as a tool to stratify pediatric T1DM
      patients according to their cardiovascular risk and to follow them up
      longitudinally.

PMID- 24020909
TI  - Effects of an oral contraceptive containing estradiol valerate and dienogest on
      circulating androgen levels and acne in young patients with PCOS: an
      observational preliminary study.
AB  - This study shows the effect of a 1 year treatment with an estradiol
      valerate/dienogest pill in 36 women suffering from polycystic ovaries and mild or
      moderate acne. At beginning of the study, 24 patients (66.7%) had grade 1-2
      (mild) acne and 12 patients (33.3%) had grade 3 (moderate) acne. After 12 cycles
      of therapy, we found an improvement of acne in 19 (52.8%) patients and a
      worsening of acne in 3 (8.4%) patients. The percentage of patients recovered was
      statistically significant (p < 0.01). SHBG levels were significantly higher after
      6 and 12 months of therapy (p < 0.001), while total testosterone levels were
      lower in all patients at 6 and 12 months although this trend did not reach
      statistical significance. In conclusion, the present study suggests that the
      E2V/DNG pill could exert a positive influence on acne and hyperandrogenism. Since
      this is an observational study on a very limited population number, additional
      randomized controlled studies on larger populations are needed also to determine
      the effects of this contraceptive over longer periods of use.

PMID- 24020910
TI  - Calcidiol [25(OH)D3]: from diagnostic marker to therapeutical agent.
AB  - OBJECTIVE: Osteoporosis is a skeletal disorder characterized by diminished bone
      strength, which results in an increased risk of fracture. Currently, osteoporosis
      is a public health priority due to the large number of individuals affected and
      the detrimental effect on quality of life. Primary osteoporosis, the most common
      form, usually results from age-related reduction in bone mineral strength. Over
      time, the individual's capacity to build bone is impaired, as the synthesis of
      vitamin D, the hormone responsible for calcium absorption, tends to decline. As
      serum calcium levels decrease, metabolic control serves to increase the removal
      of calcium from the skeleton to make up for the deficit. The synthesis of the
      'hormone' vitamin D and its control therefore become central to intervention in
      involutional osteoporosis syndromes. In humans, plain vitamin D
      (cholecalciferol), also called parental or native vitamin D, is photosynthesized
      in the skin and then hydroxylated in the liver into the vitamin D analog
      calcidiol [25(OH)D3], which is hydroxylated again in the kidney into the vitamin
      D analog calcitriol [1,25(OH)2D3]. The advantage of administering vitamin D
      analogs is that the pro-drug calcidiol avoids the effect of declines in hepatic
      function, while calcitriol avoids the effect of declines in hepatic and kidney
      function. A strategy to enhance [25(OH)D3] levels to the optimal threshold of
      vitamin D is supplementation with the calcidiol metabolite itself. The goal of
      this paper is to review published studies on the efficacy of the calcidiol
      metabolite in increasing 25(OH)D3 serum levels and improving skeletal health
      parameters in humans. METHODS: A library search of published papers in the area
      of use of calcidiol in humans from 1967 to 2013 was performed (key words:
      calcidiol, 25-hydroxy-vitamin D3, vitamin D supplementation, vitamin D
      metabolism, osteomalacia). RESULTS AND CONCLUSION: The results of the survey made
      it possible to conclude that calcidiol is characterized by a number of features
      that make the compound ideal in conditions that require supplementation with a 25
      hydroxylated metabolite.

PMID- 24020911
TI  - Deep sequencing approaches to antibody discovery.
AB  - Antibodies have become one of the dominant therapeutic platforms due to their
      safety, specificity, and efficacy. Owing to their massive potential diversity
      intrinsic to their structure, the number of possible different molecules that
      could be generated and analyzed from natural or synthetic systems is almost
      limitless. However, even with vast improvements in automation, classic antibody
      generation and analysis systems are severely limited in the number of molecules
      that can be interrogated during a typical discovery campaign. When one considers
      more complex target systems, along with the desire to isolate antibodies with
      very unique characteristics, the chances are very low that these systems will be
      successful. Next generation sequencing technologies (also referred to as "deep
      sequencing") allow for the analysis of single molecules in millions in a very
      short period of time. By applying these deep sequencing technologies to antibody
      discovery, we now have the ability to look for very specific molecules with very
      unique properties and activities, further our understanding of species and strain
      specific repertoires, and can now begin to use sequence information to identify
      function. The application of these technologies is opening the door to the
      discovery of next generation antibody therapeutics. 

PMID- 24020913
TI  - Estimation of the sensitivity of environmental sampling for detection of
      Salmonella in commercial layer flocks post-introduction of national control
      programmes.
AB  - A key element of national control programmes (NCPs) for Salmonella in commercial
      laying flocks, introduced across the European Union, is the identification of
      infected flocks and holdings through statutory sampling. It is therefore
      important to know the sensitivity of the sampling methods, in order to design
      effective and efficient surveillance for Salmonella. However, improved Salmonella
      control in response to the NCP may have influenced key factors that determine the
      sensitivity of the sampling methods used to detect Salmonella in NCPs. Therefore
      the aim of this study was to compare estimates of the sensitivity of the sampling
      methods using data collected before and after the introduction of the NCP, using
      Bayesian methods. There was a large reduction in the sensitivity of dust in non
      cage flocks between the pre-NCP studies (81% of samples positive in positive
      flocks) and post-NCP studies (10% of samples positive in positive flocks),
      leading to the conclusion that sampling dust is not recommended for detection of
      Salmonella in non-cage flocks. However, cage dust (43% of samples positive in
      positive flocks) was found to be more sensitive than cage faeces (29% of samples
      positive in positive flocks). To have a high probability of detection, several
      NCP-style samples need to be used. For confirmation of Salmonella, five NCP
      faecal samples for cage flocks, and three NCP faecal boot swab samples for non
      cage flocks would be required to have the equivalent sensitivity of the EU
      baseline survey method, which was estimated to have an 87% and 75% sensitivity to
      detect Salmonella at a 5% within-flock prevalence in cage and non-cage flocks,
      respectively.

PMID- 24020914
TI  - Systematic theoretical study of non-nuclear electron density maxima in some
      diatomic molecules.
AB  - First, exploratory calculations were performed to investigate the presence of non
      nuclear maxima (NNMs) in ground-state electron densities of homonuclear diatomic
      molecules from hydrogen up to calcium at their equilibrium geometries. In a
      second stage, only for the cases in which these features were previously
      detected, a rigorous analysis was carried out by several combinations of
      theoretical methods and basis sets in order to ensure that they are not only
      calculation artifacts. Our best results support that Li2, B2, C2, and P2 are
      molecules that possess true NNMs. A NNM was found in values obtained from the
      largest basis sets for Na2, but it disappeared at the experimental geometry
      because optimized bond lengths are significantly inaccurate for this case
      (deviations of 0.10 A). Two of these maxima are also observed in Si2 with CCSD
      and large basis sets, but they are no longer detected as core-valence correlation
      or multiconfigurational wave functions are taken into account. Therefore, the
      NNMs in Si2 can be considered unphysical features due to an incomplete treatment
      of electron correlation. Finally, we show that a NNM is encountered in LiNa,
      representing the first discovery of such electron density maxima in a
      heteronuclear diatomic system at its equilibrium geometry, to our knowledge. Some
      results for LiNa, found in variations in internuclear distances, suggest that
      molecular electric moments, such as dipole and quadrupole, are sensitive to the
      presence of NNMs. 

PMID- 24020912
TI  - Bacterial lipopolysaccharides form procollagen-endotoxin complexes that trigger
      cartilage inflammation and degeneration: implications for the development of
      rheumatoid arthritis.
AB  - INTRODUCTION: We have previously reported that bacterial toxins, especially
      endotoxins such as lipopolysaccharides (LPS), might be important causative agents
      in the pathogenesis of rheumatoid arthritis (RA) in an in vitro model that
      simulates the potential effects of residing in damp buildings. Since numerous
      inflammatory processes are linked with the nuclear factor-kappaB (NF-kappaB), we
      investigated in detail the effects of LPS on the NF-kappaB pathway and the
      postulated formation of procollagen-endotoxin complexes. METHODS: An in vitro
      model of human chondrocytes was used to investigate LPS-mediated inflammatory
      signaling. RESULTS: Immunoelectron microscopy revealed that LPS physically
      interact with collagen type II in the extracellular matrix (ECM) and anti
      collagen type II significantly reduced this interaction. BMS-345541 (a specific
      inhibitor of IkappaB kinase (IKK)) or wortmannin (a specific inhibitor of
      phosphatidylinositol 3-kinase (PI-3K)) inhibited the LPS-induced degradation of
      the ECM and apoptosis in chondrocytes. This effect was completely inhibited by
      combining BMS-345541 and wortmannin. Furthermore, BMS-345541 and/or wortmannin
      suppressed the LPS-induced upregulation of catabolic enzymes that mediate ECM
      degradation (matrix metalloproteinases-9, -13), cyclooxygenase-2 and apoptosis
      (activated caspase-3). These proteins are regulated by NF-kappaB, suggesting that
      the NF-kappaB and PI-3K pathways are involved in LPS-induced cartilage
      degradation. The induction of NF-kappaB correlated with activation of
      IkappaBalpha kinase, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65
      phosphorylation and p65 nuclear translocation. Further upstream, LPS induced the
      expression of Toll-like receptor 4 (TLR4) and bound with TLR4, indicating that
      LPS acts through TLR4. CONCLUSION: These results suggest that molecular
      associations between LPS/TLR4/collagen type II in chondrocytes upregulate the NF
      kappaB and PI-3K signaling pathways and activate proinflammatory activity.

PMID- 24020916
TI  - Structural characterization of copia-type retrotransposons leads to insights into
      the marker development in a biofuel crop, Jatropha curcas L.
AB  - BACKGROUND: Recently, Jatropha curcas L. has attracted worldwide attention for
      its potential as a source of biodiesel. However, most DNA markers have
      demonstrated high levels of genetic similarity among and within jatropha
      populations around the globe. Despite promising features of copia-type
      retrotransposons as ideal genetic tools for gene tagging, mutagenesis, and marker
      assisted selection, they have not been characterized in the jatropha genome yet.
      Here, we examined the diversity, evolution, and genome-wide organization of copia
      type retrotransposons in the Asian, African, and Mesoamerican accessions of
      jatropha, then introduced a retrotransposon-based marker for this biofuel crop.
      RESULTS: In total, 157 PCR fragments that were amplified using the degenerate
      primers for the reverse transcriptase (RT) domain of copia-type retroelements
      were sequenced and aligned to construct the neighbor-joining tree. Phylogenetic
      analysis demonstrated that isolated copia RT sequences were classified into ten
      families, which were then grouped into three lineages. An in-depth study of the
      jatropha genome for the RT sequences of each family led to the characterization
      of full consensus sequences of the jatropha copia-type families. Estimated copy
      numbers of target sequences were largely different among families, as was
      presence of genes within 5 kb flanking regions for each family. Five copia-type
      families were as appealing candidates for the development of DNA marker systems.
      A candidate marker from family Jc7 was particularly capable of detecting genetic
      variation among different jatropha accessions. Fluorescence in situ hybridization
      (FISH) to metaphase chromosomes reveals that copia-type retrotransposons are
      scattered across chromosomes mainly located in the distal part regions.
      CONCLUSION: This is the first report on genome-wide analysis and the cytogenetic
      mapping of copia-type retrotransposons of jatropha, leading to the discovery of
      families bearing high potential as DNA markers. Distinct dynamics of individual
      copia-type families, feasibility of a retrotransposon-based insertion
      polymorphism marker system in examining genetic variability, and approaches for
      the development of breeding strategies in jatropha using copia-type
      retrotransposons are discussed.

PMID- 24020915
TI  - The physical capability of community-based men and women from a British cohort:
      the European Prospective Investigation into Cancer (EPIC)-Norfolk study.
AB  - BACKGROUND: The European Working Group for Sarcopenia in Older People (EWGSOP)
      published a case-finding algorithm for sarcopenia, recommending muscle mass
      measurement in older adults with low grip strength (women <20 kg; men <30 kg) or
      slow walking speed (<=0.8 m/s). However, the implications of adopting this
      algorithm into clinical practice are unclear. Therefore, we aimed to explore the
      physical capability of men and women from a British population-based cohort
      study. METHODS: In the European Prospective Investigation into Cancer-Norfolk
      study, 8,623 community-based adults (48-92 years old) underwent assessment of
      grip strength, walking speed, timed chair stands and standing balance. The
      proportion of older men and women (>=65 years) fulfilling EWGSOP criteria for
      muscle mass measurement was estimated. Additionally, cross-sectional associations
      of physical capability with age and sex were explored using linear and logistic
      regression. RESULTS: Approximately 1 in 4 older participants (28.8%) fulfilled
      criteria for muscle mass measurement with a greater proportion of women than men
      falling below threshold criteria (33.6% versus 23.6%). Even after adjustment for
      anthropometry, women were 12.4 kg (95% Confidence Interval [CI] 12.0, 12.7)
      weaker, took 12.0% (95% CI 10.0, 14.0) longer to perform five chair stands and
      were 1.82 (95% CI 1.48, 2.23) times more likely to be unable to hold a tandem
      stand for 10 seconds than men, although usual walking speed was similar. Physical
      capability was inversely associated with age and per year, walking speed
      decreased by 0.01 m/s (95% CI 0.01, 0.01) and grip strength decreased by 0.49 kg
      (men; 95% CI 0.46, 0.51) and 0.25 kg (women; 95% CI 0.23, 0.27). Despite this,
      there was still variation within age-groups and not all older people had low
      physical capability. CONCLUSIONS: Every effort to optimise functional health in
      later life should be made since poor function is not inevitable. However, if the
      EWGSOP sarcopenia case-finding algorithm is endorsed, large proportions of older
      people could qualify for muscle mass measurement which is not commonly available.
      Considering population ageing, further discussion is needed over the utility of
      muscle mass measurement in clinical practice.

PMID- 24020917
TI  - Teaching and evaluation methods of medical ethics in the Saudi public medical
      colleges: cross-sectional questionnaire study.
AB  - BACKGROUND: Saudi Arabia is considered one of the most influential Muslim
      countries being as the host of the two most holy places for Muslims, namely
      Makkah and Madina. This was reflected in the emphasis on teaching medical ethics
      in a lecture-based format as a part of the subject of Islamic culture taught to
      medical students. Over the last few years, both teaching and evaluation of
      medical ethics have been changing as more Saudi academics received specialized
      training and qualifications in bioethics from western universities. METHODS: This
      study aims at studying the current teaching methods and evaluation tools used by
      the Saudi public medical schools. It is done using a self-administered online
      questionnaire. RESULTS: Out of the 14 medical schools that responded, the
      majority of the responding schools (6; 42.8%), had no ethics departments; but all
      schools had a curriculum dedicated to medical ethics. These curricula were mostly
      developed by the faculty staff (12; 85.7%). The most popular teaching method was
      lecturing (13; 92.8%). The most popular form of student assessment was a paper
      based final examination (6; 42.8%) at the end of the course that was allocated
      40% or more of the total grade of the ethics course. Six schools (42.8%)
      allocated 15-30% of the total grade to research. CONCLUSION: Although there is a
      growing interest and commitment in teaching ethics to medical students in Saudi
      schools; there is lack of standardization in teaching and evaluation methods.
      There is a need for a national body to provide guidance for the medical schools
      to harmonize the teaching methods, particularly introducing more interactive and
      students-engaging methods on the account of passive lecturing.

PMID- 24020918
TI  - The effect of palliative care on patient functioning.
AB  - BACKGROUND: Palliative care is increasingly viewed as a care option that should
      not only be offered to patients very near the end of life. An important question
      is whether increased use of palliative care soon after a patient's referral will
      improve patient functioning, an aspect of quality of life. OBJECTIVES: The aim of
      this study was to determine if increased use of palliative care is associated
      with increased patient functioning. METHODS: The Carolinas Palliative Care
      Database Consortium collects palliative care encounter data from a variety of
      providers, settings, and patients, and it measures patient functioning, allowing
      us to test the hypothesis that increased use of palliative care early in a
      patient's palliative care experience will improve patient functioning. RESULTS:
      After controlling for other factors that could explain patient functioning, we
      find that each additional palliative care visit during the first month of follow
      up increases patient functioning measured using an area under the curve (AUC)
      approach (0.008 per visit, p=0.01). However, patient functioning as measured at
      the initial visit is a far stronger predictor of subsequent functioning (0.52,
      p<0.001) than are additional palliative care visits. CONCLUSIONS: Increased use
      of palliative care was associated with improved patient functioning. This held
      true at very low as well as very high levels of initial functioning. The
      strongest predictor of subsequent patient functioning is their initial status.
      Accounting for patient-specific differences to precisely determine the impact of
      palliative care on patient functioning is difficult.

PMID- 24020919
TI  - Unmet quality indicators for metastatic cancer patients admitted to intensive
      care unit in the last two weeks of life.
AB  - BACKGROUND: The majority of U.S. cancer patients express the desire to die at
      home, though most do not, and are often subjected to ineffective therapies near
      the end of life (EOL). In 2008 the U.K. Department of Health and National Health
      Care Service implemented a set of 10 quality markers to improve EOL care (EOLC)
      for seriously ill persons. Data show that this intervention has had a positive
      impact on patients' EOLC. PURPOSE: The study assessed the quality of EOLC
      received by terminally ill cancer patients admitted to the intensive care unit
      (ICU) in the last two weeks of life. DESIGN: A retrospective chart review was
      done of the electronic medical record (EMR) of 2498 patients admitted to the ICU
      from January to August 2011. The six U.K. quality indicators pertaining to
      patients were used to assess quality of EOLC. SETTING: The setting was a tertiary
      academic medical center with 663 beds and 66 adult ICU beds in northern
      California. PATIENTS: EMR analysis identified 2498 patients admitted to the ICU
      during the study period--232 died within two weeks of admission. Sixty-nine
      decedents had metastatic cancer. Of the patients, 58% were male, average age 59.8
      years (range 25-91). RESULTS: Quality indicators were met in a relatively small
      percentage of patients admitted to the ICU in the last two weeks of life:
      prognostication 67%, advance care planning 32%, goals of care 42%, caregiver
      needs 0%, coordination of care across organizational boundaries 7%, and
      standardized care pathway implementation 58%. Palliative care consultations
      occurred in 28 patients. CONCLUSIONS: Quality indicators for EOLC were unmet in
      cancer patients admitted to the ICU in the last two weeks of life. Hospital-wide
      provider education about the need for early advance care planning with all
      seriously ill patients has been implemented in an effort to improve quality of
      care at EOL.

PMID- 24020920
TI  - A Canadian experience of integrating complementary therapy in a hospital
      palliative care unit.
AB  - BACKGROUND: The provision of complementary therapy in palliative care is rare in
      Canadian hospitals. An Ontario hospital's palliative care unit developed a
      complementary therapy pilot project within the interdisciplinary team to explore
      potential benefits. Massage, aromatherapy, Reiki, and Therapeutic TouchTM were
      provided in an integrated approach. This paper reports on the pilot project, the
      results of which may encourage its replication in other palliative care programs.
      OBJECTIVES: The intentions were (1) to increase patients'/families' experience of
      quality and satisfaction with end-of-life care and (2) to determine whether the
      therapies could enhance symptom management. RESULTS: Data analysis (n=31) showed
      a significant decrease in severity of pain, anxiety, low mood, restlessness, and
      discomfort (p<0.01, 95% confidence interval); significant increase in inner
      stillness/peace (p<0.01, 95% confidence interval); and convincing narratives on
      an increase in comfort. The evaluation by staff was positive and encouraged
      continuation of the program. CONCLUSIONS: An integrated complementary therapy
      program enhances regular symptom management, increases comfort, and is a valuable
      addition to interdisciplinary care.

PMID- 24020921
TI  - Intravitreal low-dosage bevacizumab for retinopathy of prematurity.
AB  - PURPOSE: To report on the therapeutic effect of intravitreal low-dose bevacizumab
      for treatment for retinopathy of prematurity (ROP). METHODS: The single-centre
      retrospective, non-comparative case series study included all infants who
      consecutively underwent intravitreal injection of 0.375 mg bevacizumab (0.03 ml)
      under light sedation in topical anaesthesia as therapy of ROP in zone I or zone
      II. RESULTS: The clinical charts of 29 patients (57 eyes) with a median birth
      weight of 630 g (range: 290-1390 g) and median gestational age of 25 + 1 weeks
      (range: 23 + 1-30 weeks) were reviewed. Six children (12 eyes) were graded as ROP
      with zone I retinopathy and plus disease. The 23 remaining infants had
      extraretinal neovascularizations in zone II or partly zone I. The intravitreal
      bevacizumab injection was injected at a median age of 12 + 1 weeks (range: 7 + 4
      21 + 4), the median follow-up was 4.2 months (range: from 3 days to 45.1 months).
      In all eyes treated, a regression of plus disease occurred within two to six
      days, retinal neovascularizations regressed within 2-3 weeks and pupillary
      rigidity improved. None except one child in exceptionally bad general health
      conditions needed a second intravitreal bevacizumab injection. In none of the
      infants, any ophthalmologic side-effects of the bevacizumab application were
      detected during the follow-up period. CONCLUSIONS: The intravitreal injection of
      a low dose of 0.375 mg bevacizumab showed a high efficacy as treatment for ROP.
      The question arises whether the low dosage of bevacizumab as compared to the
      dosage of 0.625 mg bevacizumab may be preferred.

PMID- 24020922
TI  - Aggregation of oligoarginines at phospholipid membranes: molecular dynamics
      simulations, time-dependent fluorescence shift, and biomimetic colorimetric
      assays.
AB  - A time-dependent fluorescence shift method, biomimetic colorimetric assays, and
      molecular dynamics simulations have been performed in search of explanations why
      arginine rich peptides with intermediate lengths of about 10 amino acids
      translocate well through cellular membranes, while analogous lysine rich peptides
      do not. First, we demonstrate that an important factor for efficient peptide
      adsorption, as the first prerequisite for translocation across the membrane, is
      the presence of negatively charged phospholipids in the bilayer. Second, we
      observe a strong tendency of adsorbed arginine (but not lysine) containing
      peptides to aggregate at the bilayer surface. We suggest that this aggregation of
      oligoarginines leads to partial disruption of the bilayer integrity due to the
      accumulated large positive charge at its surface, which increases membrane
      surface interactions due to the increased effective charge of the aggregates. As
      a result, membrane penetration and translocation of medium length oligoarginines
      becomes facilitated in comparison to single arginine and very long polyarginines,
      as well as to lysine containing peptides. 

PMID- 24020923
TI  - The impact of pelvic floor surgery on female sexual function: a mixed
      quantitative and qualitative study.
AB  - OBJECTIVE: To assess whether the current condition-specific sexual function
      questionnaire provides full insight into sexual function following pelvic floor
      surgery. DESIGN: Prospective, mixed quantitative and qualitative study. SETTING:
      Urogynaecology clinic in a large university hospital. POPULATION: Thirty-seven
      women undergoing surgery for pelvic organ prolapse (POP) and/or stress urinary
      incontinence (SUI). METHODS: Women were seen before surgery and 3 months
      postoperatively. At both visits the Pelvic Organ Prolapse/Urinary Incontinence
      Sexual Function Questionnaire (PISQ) was completed and a qualitative face-to-face
      semi-structured interview was conducted. PISQ total and domain scores, as well as
      the change in the preoperative and postoperative score, were calculated and
      analysed using Wilcoxon signed rank test and one-sample t-test. The qualitative
      data were systematically analysed using data-matrices. MAIN OUTCOME MEASURES: The
      impact of pelvic floor surgery on female sexual function. RESULTS: Significant
      improvement was seen for PISQ total score (P = 0.003) as well as Physical (P <
      0.001) and Partner-related (P = 0.002) domains, but not for the
      Behavioural/Emotive domain (P = 0.220). Analysis of qualitative data showed that
      improvement in sexual function was a result of cure of POP and SUI symptoms.
      Deterioration of sexual function was due to dyspareunia, fear of causing damage
      to the surgical result, new symptoms and a disappointing result of surgery.
      CONCLUSIONS: Our qualitative data show that PISQ is limited in the assessment of
      sexual function after pelvic floor surgery as it does not assess most surgery
      specific negative effects on sexual function.

PMID- 24020924
TI  - Decreasing incidence of AA amyloidosis in Spain.

PMID- 24020925
TI  - DNA repair gene polymorphisms and risk of head and neck cancer in the Tunisian
      population.
AB  - Altered activity of DNA repair enzymes may be involved in modulating cancer
      susceptibility and pathogenesis of head and neck cancer (HNC). We conducted a
      case-control study to test the association between three common single-nucleotide
      polymorphisms of XRCC1, ERCC2, and ERCC3 genes with HNC risk in Tunisian
      patients. To the best of our knowle dge, this is the first report on
      polymorphisms in XRCC1, ERCC2, and ERCC3 and susceptibility to HNC in our
      population. The genotype analyses of XRCC1 Arg399Gln, ERCC2 Lys751Gln, and ERCC3
      7122 A>G polymorphisms for 169 HNC patients, and 261 controls were performed
      using the PCR-based restriction fragment length polymorphism. Stratification of
      the populations according to smoking and drinking habits and occupational
      exposure highlighted the importance of tobacco, alcohol, and toxic substance as
      three risk co-factors for the development of HNC. Our study suggests that only
      the XRCC1 Arg399Gln polymorphism was associated with the risk of HNC in the
      Tunisian population (OR = 2.04; P = 0.001). Furthermore, the risk of HNC was
      associated with XRCC1 Arg399Gln polymorphism stratified by occupational exposure
      status (OR = 2.29; P = 0.024). However, no statistically significant association
      was observed between the risk of developing HNC and the ERCC2 Lys751Gln and ERCC3
      A>G polymorphisms. These data suggest that the XRCC1 Arg399Gln polymorphism is
      associated with an increased risk of developing HNC, because it correlates with
      occupational exposure in Tunisian population.

PMID- 24020932
TI  - Synthesis and evaluation of l-rhamnose 1C-phosphonates as
      nucleotidylyltransferase inhibitors.
AB  - We report the synthesis of a series of phosphonates and ketosephosphonates
      possessing an L-rhamnose scaffold with varying degrees of fluorination. These
      compounds were evaluated as potential inhibitors of alpha-D-glucose 1-phosphate
      thymidylyltransferase (Cps2L), the first enzyme in Streptococcus pneumoniae L
      rhamnose biosynthesis, and a novel antibiotic target. Enzyme-substrate and enzyme
      inhibitor binding experiments were performed using water-ligand observed binding
      via gradient spectroscopy (WaterLOGSY) NMR for known sugar nucleotide substrates
      and selected phosphonate analogues. IC50 values were measured and Ki values were
      calculated for inhibitors. New insights were gained into the binding promiscuity
      of enzymes within the prokaryotic L-rhamnose biosynthetic pathway (Cps2L, RmlB-D)
      and into the mechanism of inhibition for the most potent inhibitor in the series,
      L-rhamnose 1C-phosphonate.

PMID- 24020926
TI  - The PKR activator, PACT, becomes a PKR inhibitor during HIV-1 replication.
AB  - BACKGROUND: HIV-1 translation is modulated by the activation of the interferon
      (IFN)-inducible Protein Kinase RNA-activated (PKR). PKR phosphorylates its
      downstream targets, including the alpha subunit of the eukaryotic translation
      Initiation Factor 2 (eIF2alpha), which decreases viral replication. The PKR
      Activator (PACT) is known to activate PKR after a cellular stress. In lymphocytic
      cell lines, HIV-1 activates PKR only transiently and not when cells replicate the
      virus at high levels. The regulation of this activation is due to a combination
      of viral and cellular factors that have been only partially identified. RESULTS:
      PKR is transiently induced and activated in peripheral blood mononuclear cells
      after HIV-1 infection. The addition of IFN reduces viral replication, and induces
      both the production and phosphorylation of PKR. In lymphocytic Jurkat cells
      infected by HIV-1, a multiprotein complex around PKR contains the double-stranded
      RNA binding proteins (dsRBPs), adenosine deaminase acting on RNA (ADAR)1 and
      PACT. In HEK 293T cells transfected with an HIV-1 molecular clone, PACT
      unexpectedly inhibited PKR and eIF2alpha phosphorylation and increased HIV-1
      protein expression and virion production in the presence of either endogenous PKR
      alone or overexpressed PKR. The comparison between different dsRBPs showed that
      ADAR1, TAR RNA Binding Protein (TRBP) and PACT inhibit PKR and eIF2alpha
      phosphorylation in HIV-infected cells, whereas Staufen1 did not. Individual or a
      combination of short hairpin RNAs against PACT or ADAR1 decreased HIV-1 protein
      expression. In the astrocytic cell line U251MG, which weakly expresses TRBP, PACT
      mediated an increased HIV-1 protein expression and a decreased PKR
      phosphorylation. In these cells, a truncated PACT, which constitutively activates
      PKR in non-infected cells showed no activity on either PKR or HIV-1 protein
      expression. Finally, PACT and ADAR1 interact with each other in the absence of
      RNAs. CONCLUSION: In contrast to its previously described activity, PACT
      contributes to PKR dephosphorylation during HIV-1 replication. This activity is
      in addition to its heterodimer formation with TRBP and could be due to its
      binding to ADAR1. HIV-1 has evolved to replicate in cells with high levels of
      TRBP, to induce the expression of ADAR1 and to change the function of PACT for
      PKR inhibition and increased replication.

PMID- 24020931
TI  - TCR repertoire analysis by next generation sequencing allows complex differential
      diagnosis of T cell-related pathology.
AB  - Clonotype analysis is essential for complete characterization of antigen-specific
      T cells. Moreover, knowledge on clonal identity allows tracking of antigen
      specific T cells in whole blood and tissue infiltrates and can provide
      information on antigenic specificity. Here, we developed a next generation
      sequencing (NGS)-based platform for the highly quantitative clonotype
      characterization of T cells and determined requirements for the unbiased
      characterization of the input material (DNA, RNA, ex vivo derived or cell culture
      expanded T cells). Thereafter we performed T cell receptor (TCR) repertoire
      analysis of various specimens in clinical settings including cytomegalovirus
      (CMV), polyomavirus BK (BKV) reactivation and acute cellular allograft rejection.
      Our results revealed dynamic nature of virus-specific T cell clonotypes; CMV
      reactivation was linked to appearance of new highly abundant antigen-specific
      clonalities. Moreover, analysis of clonotype overlap between BKV-, alloantigen
      specific T cell-, kidney allograft- and urine-derived lymphocytes provided hints
      for the differential diagnosis of allograft dysfunction and enabled appropriate
      therapy adjustment. We believe that the established approach will provide
      insights into the regulation of virus-specific/anti-tumor immunity and has high
      diagnostic potential in the clinical routine. 

PMID- 24020933
TI  - Definitions of love in a sample of British women: an empirical study using Q
      methodology.
AB  - Social psychological research has increasingly acknowledged that any pretensions
      to a singular theory of love should be replaced with a concern about its
      affirmation and what people actually say and do in love's name. Lee's (1977) love
      styles research and Sternberg's (1995) theory of love as a story are prime
      examples. Despite traditional definitions of love in western cultures being
      dominated by feminine images and tales of gender difference, however, the
      personal definitions and experiences of women have received comparatively little
      empirical attention, particularly in recent years and despite some well
      documented changes in their cultural circumstances. This study remedies that
      situation through presentation of a Q methodological study in which a convenience
      sample of 59 British women were asked to Q sort 54 single-word descriptors of
      love to define love as they had experienced it. Factor analysis of the resulting
      Q sorts revealed six distinct definitions of love, interpreted as 'attraction,
      passion & romance', 'unconditional love', 'sex & fun', 'friendship &
      spirituality', 'a permanent commitment', and 'separate people, separate lives'.
      The six definitions are then discussed in terms of their allegiance to
      traditionally feminine and/or masculine values and as a means of highlighting the
      changing face of Britain's relational culture. 

PMID- 24020934
TI  - Novel codon insert in HIV type 1 clade B reverse transcriptase associated with
      low-level viremia during antiretroviral therapy.
AB  - We investigated the pol genotype in two phylogenetically and epidemiologically
      linked partners, who were both experiencing persistent low-level viremia during
      antiretroviral therapy. In one partner we identified a new residue insertion
      between codon 248 and 249 of the HIV-1 RNA reverse transcriptase (RT) coding
      region (HXB2 numbering). We then investigated the potential impact of identified
      mutations in RT and antiretroviral binding affinity using a novel computational
      approach.

PMID- 24020935
TI  - Effectiveness of influenza vaccine in children in day-care centers of Sapporo.
AB  - BACKGROUND: We conducted a retrospective cohort study for evaluating the
      effectiveness of the trivalent inactivated influenza vaccine (TIV) among children
      aged 0-6 years in the 2011-2012 season in Sapporo City, Japan, because of scarce
      evidence. METHODS: From 10 day-care centers in Sapporo City, Japan, 629 parents
      participated in the study. Each parent of the subjects described whether a
      subject received TIV once or twice in the 2011-2012 season, as well as the exact
      dates of receiving TIV from records in a maternal and child health handbook
      marked by a pediatrician. The incidence of influenza was defined as being
      affected with influenza as diagnosed by a pediatrician. Cox's proportional model
      was used for calculating a hazard ratio (HR) and its 95% confidence interval
      (95%CI) of TIV on an influenza incidence. RESULTS: After adjusting potential
      confounding variables, such as the day-care center, presence of comorbidity, size
      of household, number of siblings, and number of smokers in the home in addition
      to the age and sex of the child, HR was significantly reduced in the subjects
      aged 1 year (HR = 0.22, 95%CI 0.09-0.54) as well as in the total subjects (HR =
      0.72, 95%CI 0.52-0.99). Consequently, the effectiveness of TIV was calculated as
      78% for the subjects aged 1 year and 28% for the total subjects. CONCLUSION: Our
      study suggests that TIV is effective, especially in subjects aged 1 year. Further
      studies are necessary in different seasons, places, and populations to clarify
      the effectiveness of the influenza vaccine in children.

PMID- 24020936
TI  - Evaluation of the 2007 WHO guideline to diagnose smear negative tuberculosis in
      an urban hospital in Ethiopia.
AB  - BACKGROUND: The 2007 World Health Organization (WHO) guideline to diagnose smear
      negative tuberculosis (TB) in HIV-prevalent settings was mainly based on expert
      advice and therefore requires evaluation in real life situations. METHODS: In
      2009, this guideline was introduced at the ALERT hospital in Ethiopia. From
      October 2009 to January 2011, the accuracy of the guideline was evaluated using
      Mycobacterium tuberculosis culture positivity as reference standard in HIV
      positive TB suspects. RESULTS: A total of 459 TB suspects were enrolled during
      the study period; 336 (73.2%) were HIV positive. Acid fast bacilli sputum smear
      microscopy was done for 74.7% (251/336) HIV positive TB suspects; 94.4% (237/251)
      were smear negative. A chest X-ray was performed in 92.8% (220/237) and a
      Mycobacterium tuberculosis culture in 63.7% (151/237). The median TB diagnostic
      delay for smear negative cases was 3 days (interquartile range 3-4 days). Of the
      75 patients diagnosed with smear negative pulmonary TB, 89. 4% (67/75) were
      diagnosed by chest X-ray, 9.4% (7/75) by culture and 1.3% (1/75) by clinical
      suspicion only. In 147 smear negative TB suspects Mycobacterium tuberculosis
      culture and chest X-ray results were available. Among these 147 patients, the
      sensitivity of the chest X-ray to diagnose smear negative TB in HIV-positive TB
      suspects was 53.3% (95% CI: 26.7-78.7); the specificity 67.4% (95% CI: 58.7
      75.3). CONCLUSION: The 2007 WHO diagnostic algorithm for the diagnosis of smear
      negative TB is likely to reduce the diagnostic delay and therefore decrease
      morbidity and mortality of TB in a HIV prevalent settings like Ethiopia.

PMID- 24020937
TI  - Cardiovascular disease risk in young Indian women with polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is associated with significant risk factors for
      cardiovascular disease (CVD) like insulin resistance, hyperinsulinism,
      hypertension and dyslipidemia. We studied CVD risk in young women (18-35 years
      age) with PCOS using carotid intima media thickness (CIMT) and brachial artery
      flow mediated dilation (FMD) which are markers of subclinical atherosclerosis.
      Fifty women with PCOS (age: 24.3 +/- 4 years; body mass index [BMI]: 24.6 +/- 4
      kg/m(2)) were compared with 50 age and BMI matched healthy controls (age: 24.6 +/
      5 years; BMI: 23.9 +/- 4 kg/m(2)). CIMT was significantly higher (0.55 +/- 0.09
      mm versus 0.40 +/- 0.1 mm, p value <0.0001) and FMD was significantly lower (9.39
      +/- 4.36% versus 13.89 +/- 4.77%, p value <0.0001) in cases as compared to
      controls. These differences in CIMT and FMD remained significant when subgroup
      were analyzed, obese PCOS versus obese controls and non obese PCOS versus non
      obese controls. In stepwise linear regression PCOS was associated with CIMT and
      FMD independent of age, BMI and blood pressure. Young women with PCOS
      irrespective of their BMI have evidence for increased CVD risk as shown by
      increased CIMT and a lower FMD.

PMID- 24020938
TI  - QT interval prolongation and the risk of torsades de pointes: essentials for
      clinicians.
AB  - OBJECTIVE: QT interval prolongation signifies an increased risk of the life
      threatening arrhythmia torsades de pointes (TdP). The purpose of this paper is to
      review the diverse methods for assessing and monitoring the risk of TdP, discuss
      risk factors for TdP, and recommend interventions that may mitigate the risk of
      TdP. METHODS: A non-systematic search of PubMed (through March 2013) was
      conducted to determine the optimal approach to assessing and monitoring QT
      interval, prevention of TdP, and to identify risks factors for TdP. Papers known
      to the authors were included, as were scientific statements. Articles were chosen
      based on the judgment of the authors. RESULTS: Risk factors for drug-induced TdP
      include hypokalemia, female sex, drug-drug interactions, advancing age, genetic
      predisposition, hypomagnesemia, heart failure, bradycardia, and corrected QT
      (QTc) interval prolongation. Many risk factors, including hypokalemia, use of QT
      interval-prolonging drugs, and drug interactions are potentially modifiable and
      should be corrected in persons at risk for QT interval prolongation. Given the
      variable onset of TdP following initiation of QT-interval-prolonging drugs,
      careful and regular monitoring of electrocardiography (EKG) and electrolytes are
      necessary. Patients at risk for QT interval prolongation should be educated to go
      directly to the emergency room if they experience palpitations, lightheadedness,
      dizziness or syncope. When the QTc interval is 470-500 ms for males, or 480-500
      ms for females, or the QTc interval increases 60 ms or more from pretreatment
      values, dose reduction or discontinuation of the offending drug should be
      considered where possible, and electrolytes corrected as needed. Furthermore, if
      the QTc interval is >=500 ms, the offending drug should be discontinued, and
      continuous EKG telemetry monitoring should be performed, or the 12-lead EKG
      should be repeated every 2-4 hours, until the QT interval has normalized.
      CONCLUSIONS: Close monitoring for QTc prolongation is necessary to prevent TdP.
      The recommendations in this paper are limited by the available evidence and
      additional studies are needed to better define the approach to monitoring.

PMID- 24020940
TI  - Catalyst-controlled aliphatic C-H oxidations with a predictive model for site
      selectivity.
AB  - Selective aliphatic C-H bond oxidations may have a profound impact on synthesis
      because these bonds exist across all classes of organic molecules. Central to
      this goal are catalysts with broad substrate scope (small-molecule-like) that
      predictably enhance or overturn the substrate's inherent reactivity preference
      for oxidation (enzyme-like). We report a simple small-molecule, non-heme iron
      catalyst that achieves predictable catalyst-controlled site-selectivity in
      preparative yields over a range of topologically diverse substrates. A catalyst
      reactivity model quantitatively correlates the innate physical properties of the
      substrate to the site-selectivities observed as a function of the catalyst. 

PMID- 24020939
TI  - Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker-
      longitudinal relationships with pain and structural changes: data from the
      Osteoarthritis Initiative.
AB  - INTRODUCTION: Bone marrow lesion (BML) size may be an important imaging biomarker
      for osteoarthritis-related clinical trials and reducing BML size may be an
      important therapeutic goal. However, data on the interrelationships between BML
      size, pain, and structural progression are inconsistent and rarely examined in
      the same cohort. Therefore, we evaluated the cross-sectional and longitudinal
      associations of BML volume with knee pain and joint space narrowing (JSN).
      METHODS: A BML volume assessment was performed on magnetic resonance images of
      the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from
      a convenience sample of 404 participants in the progression cohort. During the
      same visits, knee pain was assessed with WOMAC pain scores and knee radiographs
      were acquired and scored for JSN. BML volume was summed to generate a total knee
      volume and an index tibiofemoral compartment volume (compartment with greater
      baseline JSN). Primary analyses included multiple linear regressions (outcome =
      pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN,
      predictor = index tibiofemoral compartment BML volume). RESULTS: This sample was
      49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had
      radiographic osteoarthritis in the study knee. Larger baseline BMLs were
      associated with greater baseline knee pain (P = 0.01), the presence of JSN at
      baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83),
      and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML
      volume had a positive association with changes in knee pain severity (P = 0.004)
      and this association may be driven by knees that were progressing from no or
      small baseline BMLs to larger BMLs. In contrast, we found no linear positive
      relationship between BML volume change and JSN progression. Instead, regression
      of medial tibiofemoral BML volume was associated with JSN progression compared to
      knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28).
      However, follow-up analyses indicated that the association between JSN
      progression and BML volume change may primarily be influenced by baseline BML
      volume. CONCLUSION: Large baseline BMLs are associated with greater baseline knee
      pain, the presence of JSN at baseline, and disease progression. Additionally, BML
      regression is associated with decreased knee pain but not a reduced risk of
      concurrent JSN progression.

PMID- 24020941
TI  - Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted
      tilapia metallothionein.
AB  - BACKGROUND: Though n-butanol has been proposed as a potential transportation
      biofuel, its toxicity often causes oxidative stress in the host microorganism and
      is considered one of the bottlenecks preventing its efficient mass production.
      RESULTS: To relieve the oxidative stress in the host cell, metallothioneins
      (MTs), which are known as scavengers for reactive oxygen species (ROS), were
      engineered in E. coli hosts for both cytosolic and outer-membrane-targeted
      (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from
      human (HMT), mouse (MMT), and tilapia fish (TMT) were tested. The host strain
      expressing membrane-targeted TMT showed the greatest ability to reduce oxidative
      stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, and
      nickel. The same strain also allowed for an increased growth rate of recombinant
      E. coli under n-butanol stress. Further experiments indicated that the TMT-fused
      OmpC protein could not only function in ROS scavenging but also regulate either
      glycine betaine (GB) or glucose uptake via osmosis, and the dual functional
      fusion protein could contribute in an enhancement of the host microorganism's
      growth rate. CONCLUSIONS: The abilities of scavenging intracellular or
      extracellular ROS by these engineering E. coli were examined, and TMT show the
      best ability among three MTs. Additionally, the membrane-targeted fusion protein,
      OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is
      only 1%. These results presented indicate potential novel approaches for
      engineering stress tolerant microorganism strains.

PMID- 24020942
TI  - Pregnancy week at delivery and the risk of shoulder dystocia: a population study
      of 2,014,956 deliveries.
AB  - OBJECTIVE: To study whether pregnancy week at delivery is an independent risk
      factor for shoulder dystocia. DESIGN: Population study. SETTING: Medical Birth
      Registry of Norway. POPULATION: All vaginal deliveries of singleton offspring in
      cephalic presentation in Norway during 1967 through 2009 (n = 2,014,956).
      METHODS: The incidence of shoulder dystocia was calculated according to pregnancy
      week at delivery. The associations of pregnancy week at delivery with shoulder
      dystocia were estimated as crude and adjusted odds ratios using logistic
      regression analyses. We repeated the analyses in pregnancies with and without
      maternal diabetes. MAIN OUTCOME MEASURES: Shoulder dystocia at delivery. RESULTS:
      The overall incidence of shoulder dystocia was 0.73% (n = 14,820), and the
      incidence increased by increasing pregnancy week at delivery. Birthweight was
      strongly associated with shoulder dystocia. After adjustment for birthweight,
      induction of labour, use of epidural analgesia at delivery, prolonged labour,
      forceps-assisted and vacuum-assisted delivery, parity, period of delivery and
      maternal age in multivariable analyses, the adjusted odds ratios for shoulder
      dystocia were 1.77 (1.42-2.20) for deliveries at 32-35 weeks of gestation, and
      0.84 (0.79-0.88) at 42-43 weeks of gestation, using weeks 40-41 as the reference.
      In pregnancies affected by diabetes (n = 11,188), the incidence of shoulder
      dystocia was 3.95%, and after adjustment for birthweight the adjusted odds ratio
      for shoulder dystocia was 2.92 (95% CI 1.54-5.52) for deliveries at weeks 32-35
      of gestation, and 0.91 (95% CI 0.50-1.66) at 42-43 weeks of gestation.
      CONCLUSION: The risk of shoulder dystocia was associated with increased
      birthweight, diabetes, induction of labour, use of epidural analgesia at
      delivery, prolonged labour, forceps-assisted and vacuum-assisted delivery, parity
      and period of delivery but not with post-term delivery.

PMID- 24020943
TI  - Sick sinus syndrome: a family study.
AB  - A case of related individuals affected by sick sinus syndrome is presented in
      this study. The clinical and electrocardiographic signs of sinus node dysfunction
      and the most common causes of this disease are presented. Subsequently, the
      article includes descriptions of sinus node disease in three related children as
      well as details of the disease in their relatives. A literature review of the
      genetics of familial sinus node dysfunction concludes the study. 

PMID- 24020944
TI  - Programmatic assessment of competency-based workplace learning: when theory meets
      practice.
AB  - BACKGROUND: In competency-based medical education emphasis has shifted towards
      outcomes, capabilities, and learner-centeredness. Together with a focus on
      sustained evidence of professional competence this calls for new methods of
      teaching and assessment. Recently, medical educators advocated the use of a
      holistic, programmatic approach towards assessment. Besides maximum facilitation
      of learning it should improve the validity and reliability of measurements and
      documentation of competence development. We explored how, in a competency-based
      curriculum, current theories on programmatic assessment interacted with
      educational practice. METHODS: In a development study including evaluation, we
      investigated the implementation of a theory-based programme of assessment.
      Between April 2011 and May 2012 quantitative evaluation data were collected and
      used to guide group interviews that explored the experiences of students and
      clinical supervisors with the assessment programme. We coded the transcripts and
      emerging topics were organised into a list of lessons learned. RESULTS: The
      programme mainly focuses on the integration of learning and assessment by
      motivating and supporting students to seek and accumulate feedback. The
      assessment instruments were aligned to cover predefined competencies to enable
      aggregation of information in a structured and meaningful way. Assessments that
      were designed as formative learning experiences were increasingly perceived as
      summative by students. Peer feedback was experienced as a valuable method for
      formative feedback. Social interaction and external guidance seemed to be of
      crucial importance to scaffold self-directed learning. Aggregating data from
      individual assessments into a holistic portfolio judgement required expertise and
      extensive training and supervision of judges. CONCLUSIONS: A programme of
      assessment with low-stakes assessments providing simultaneously formative
      feedback and input for summative decisions proved not easy to implement. Careful
      preparation and guidance of the implementation process was crucial. Assessment
      for learning requires meaningful feedback with each assessment. Special attention
      should be paid to the quality of feedback at individual assessment moments.
      Comprehensive attention for faculty development and training for students is
      essential for the successful implementation of an assessment programme.

PMID- 24020945
TI  - Male involvement in sexual and reproductive health in the Mendi district,
      Southern Highlands province of Papua New Guinea: a descriptive study.
AB  - BACKGROUND: Lack of male involvement and support for sexual and reproductive
      health services is seen by many Papua New Guinean women as a barrier to accessing
      services. Poor utilization of services by both men and women is reflected in high
      maternal mortality and high rates of HIV/AIDS and sexually transmitted infections
      in the Southern Highlands Province. It is therefore important to understand the
      type of services provided, men's perceptions of these services and the Health
      Sector's capacity to involve men in its programs. METHODS: Information from
      interviews of married men, officers in charge of health facilities, and
      information from a focus group discussion with village leaders was collected to
      assess possible constraints to reproductive and sexual health care delivery.
      RESULTS: Although many men had heard about antenatal care, supervised births,
      family planning and sexually transmitted infections including, HIV/AIDS, many
      were unaware of their importance and of the types of services provided to address
      these issues. There was a very strong association between men's literacy and
      their knowledge of Sexual and Reproductive Health (SRH) issues, their discussion
      of these issues with their wives and their wives' utilisation of sexual and
      reproductive health services. Some men considered SRH services to be important
      but gave priority to social obligations. Although men made most decisions for
      sexual and reproductive issues, pregnancy, child birth and rearing of children
      were regarded as women's responsibilities. Knowledge of HIV/AIDS appeared to have
      changed sexual behaviour in some men. Services for men in this rural setting were
      inadequate and service providers lacked the capacity to involve men in
      reproductive health issues. CONCLUSION: Poor knowledge, socio-cultural factors
      and inadequate and inappropriate services for men hampered utilization of
      services and impaired support for their wives' service utilization. Programmatic
      and policy initiatives should focus on improving service delivery to accommodate
      men in sexual and reproductive health.

PMID- 24020946
TI  - Immunohistochemical analysis of extracellular matrix bleb capsules of functioning
      and non-functioning glaucoma drainage implants.
AB  - PURPOSE: To detect by immunohistochemical means the changes in bleb capsules at
      the cellular level between functioning and non-functioning glaucoma drainage
      implants (GDIs). METHODS: Three samples each of functioning (1 Baerveldt and 2
      Molteno implants) and non-functioning filtration blebs (1 Molteno and 2 Ahmed
      implants) were studied. A non-functioning bleb was defined as an intra-ocular
      pressure (IOP) >21 mmHg or a <20% reduction in IOP from baseline on three
      consecutive follow-up visits with maximal tolerated medication. The capsules were
      obtained between 6 and 108 months after GDI insertion for medical reasons only.
      Primary antibodies were used to stain fibronectin, tenascin, laminin, collagen IV
      and smooth muscle actin (SMA). The samples were graded on the basis of the
      intensity and quantity of immunohistochemical staining into four categories as
      follows: no staining or a mild, moderate or marked staining. RESULTS: The non
      functioning blebs expressed more fibronectin, tenascin and SMA through the whole
      capsule wall than the functioning blebs. In the functioning blebs, tenascin was
      found mainly in the inner layer of the capsule. More type IV collagen and laminin
      were also found in the non-functioning bleb capsules than in the functioning
      blebs. No difference was found between the bleb capsules irrespective of whether
      they had been perfused with aqueous humour immediately after surgery (Ahmed) or
      after a delay (Molteno, Baerveldt). CONCLUSION: Accumulation of extracellular
      matrix components and activated fibroblasts in the bleb capsules of non
      functioning GDI indicates the presence of an active wound healing process,
      suggesting a possible reduction in filtration through the bleb wall.

PMID- 24020948
TI  - The roles of dihydrogen bonds in amine borane chemistry.
AB  - A dihydrogen bond (DHB) is an electrostatic interaction between a protonic
      hydrogen and a hydridic hydrogen. Over the past two decades, researchers have
      made significant progress in the identification and characterization of DHBs and
      their properties. In comparison with conventional hydrogen bonds (HBs), which
      have been widely used in catalysis, molecular recognition, crystal engineering,
      and supramolecular synthesis, chemists have only applied DHBs in very limited
      ways. Considering that DHBs and conventional HBs have comparable strength, DHBs
      could be more widely applied in chemistry. Over the past several years, we have
      explored the impact of DHBs on amine borane chemistry and the syntheses and
      characterization of amine boranes and ammoniated metal borohydrides for hydrogen
      storage. Through systematic computational and experimental investigations, we
      found that DHBs play a dominant role in dictating the reaction pathways (and thus
      different products) of amine boranes where oppositely charged hydrogens coexist
      for DHB formation. Through careful experiments, we observed, for the first time,
      a long-postulated reaction intermediate, ammonia diborane (AaDB), whose behavior
      is essential to mechanistic understanding of the formation of the diammoniate of
      diborane (DADB) in the reaction of ammonia (NH3) with tetrahydrofuran borane
      (THF.BH3). The formation of DADB has puzzled the boron chemistry community for
      decades. Mechanistic insight enabled us to develop facile syntheses of
      aminodiborane (ADB), ammonia borane (AB), DADB, and an inorganic butane analog
      NH3BH2NH2BH3 (DDAB). Our examples, together with those in the literature,
      reinforce the fact that DHB formation and subsequent molecular hydrogen
      elimination are a viable approach for creating new covalent bonds and
      synthesizing new materials. We also review the strong effects of DHBs on the
      stability of conformers and the hydrogen desorption temperatures of boron
      nitrogen compounds. We hope that this Account will encourage further applications
      of DHBs in molecular recognition, host-guest chemistry, crystal engineering,
      supramolecular chemistry, molecular self-assembly, chemical kinetics, and the
      syntheses of new advanced materials. 

PMID- 24020955
TI  - ASIC3: first the heartache, now a migraine!

PMID- 24020947
TI  - Cetuximab inhibits oral squamous cell carcinoma invasion and metastasis via
      degradation of epidermal growth factor receptor.
AB  - Cetuximab (Erbitux, C225) is a chimeric monoclonal antibody that binds to the
      extracellular domain of epidermal growth factor receptor (EGFR), inhibiting tumor
      growth, invasion, angiogenesis and metastasis. However, the mechanisms underlying
      the effect of Cetuximab in human oral squamous cell carcinoma (OSCC) remain
      unclear. Here, we report that Cetuximab modulates EGFR protein stability through
      the ubiquitin/proteasome pathway, resulting in the inhibition of human OSCC
      growth. Cetuximab significantly inhibited the migration and invasion of human
      OSCC cells by blocking epithelial/mesenchymal transition (EMT) and the AKT and
      ERK pathways. Furthermore, Cetuximab-inhibited cell growth by modulating the
      expression of integrin beta5. Taken together, these results provide novel
      insights into the mechanism of Cetuximab action and suggest potential therapeutic
      strategies for OSCC. 

PMID- 24020956
TI  - Prevention of migraine.
AB  - Preventing migraines, decreasing their frequency, intensity, or severity, or even
      making them more responsive to acute medications are important goals for every
      migraine sufferer. Ideally, the choice of preventive strategy should be matched
      to the individual patient. Many times preventive medications can help treat
      another problem, such as high blood pressure, depression, anxiety, or trouble
      sleeping. A preventive strategy is best formulated with a team approach involving
      the patient and caregiver, balancing effectiveness, side effects, and potential
      nonmigraine benefits.

PMID- 24020957
TI  - Excited state charge redistribution and dynamics in the donor-pi-acceptor flavin
      derivative ABFL.
AB  - Chromophores containing a donor-pi-acceptor (D-pi-A) motif have been shown to
      exhibit many interesting photophysical properties. The lowest electronic
      transition of a flavin derivative containing this motif, azobenzylflavin (ABFL),
      has previously been shown to be highly sensitive to solvent environment and
      hydrogen bonding ligands. To better understand this sensitivity, we have
      investigated the excited state charge redistribution and dynamics of ABFL in a
      low-dielectric, non-hydrogen bonding solvent by steady-state Stark and
      femtosecond optical transient absorption spectroscopies. The Stark measurements
      reveal the difference dipole moment, DeltaMU01, between the ground and first
      excited states to be 22.3 +/- 0.9 D. The direction of DeltaMU01 in the molecular
      frame was assigned with the aid of TD-DFT and finite field calculations,
      verifying the hypothesis that electron density moves from the diethylaniline
      donor to the flavin acceptor in the excited state. The magnitude of the
      difference dipole moment was used to estimate the hyperpolarizability of ABFL,
      beta0 = 720 * 10(-30) esu. Subsequent excited state decay via charge
      recombination was shown to take place in a few picoseconds. The data was best fit
      to a kinetic model composed of a sub-picosecond internal conversion step from S2
      >S1, followed by a 5 ps decay to the ground state. A competing process involving
      formation of an additional long-lived state from S1 was also observed. Cyclic
      voltammetry shows one oxidation and two reduction waves and is completely
      reversible. This analysis lays the groundwork for developing new flavin dyads
      with the desired excited electronic state properties for applications such as
      nonlinear optical devices, molecular electronics applications, or dye-sensitized
      solar cells.

PMID- 24020958
TI  - Abstracts of presentations at the 2013 potomac division meeting.

PMID- 24020959
TI  - Preparation of semisynthetic lipoproteins with fluorescent cholesterol anchor and
      their introduction to the cell membrane with minimal disruption of the membrane.
AB  - The exogenous introduction of fluorescent lipoproteins into cell membranes is a
      method for visualizing the cellular traffic of membrane associated proteins, and
      also for altering the cell surface in a controlled manner. In order to achieve
      the cell membrane anchoring of proteins and their subsequent fluorescence based
      detection, a cholesterol derivative was designed. The headgroup of the novel
      cholesterol anchor contains a fluorescent reporter and a thiol reactive maleimide
      for protein conjugation. Protein conjugation was demonstrated by the addition of
      a green fluorescent maleimido anchor to the C-terminus of a Cys extended red
      fluorescent protein, mCherry. The resulting dual fluorescent cholesteryl
      lipoprotein was successfully separated from the micellar associates of the
      surplus fluorescent lipid anchor without denaturing the protein, and the
      lipoprotein containing only the covalently linked, stoichiometric fluorescent
      lipid was efficiently delivered to the plasma membrane of live cells. It was
      demonstrated that the membrane fluorescence could be directly assigned to the
      protein-anchor conjugate, because no excess of fluorescent lipid species were
      present during the imaging experiment and the protein and anchor fluorescence
      colocalized in the cell membrane. Molecular dynamics simulations and subsequent
      trajectory analysis suggest also the spontaneous and stable membrane association
      of the cholesterol anchor. Thus, the method could be beneficially applied for
      studying membrane associated proteins and for preparing mimetics of
      glycosylphosphatidylinositol (GPI)-anchored proteins to target cholesterol-rich
      membrane microdomains. 

PMID- 24020960
TI  - Emitting state of 5-hydroxyindole, 5-hydroxytryptophan, and 5-hydroxytryptophan
      incorporated in proteins.
AB  - 5-Hydroxy-L-tryptophan (5HW) has been biosynthetically incorporated in many
      proteins to facilitate their characterization using fluorescence spectroscopy. An
      attractive feature of this tryptophan analogue is its absorbance at 310-320 nm,
      allowing its specific excitation in a Trp background. The red-shift in absorbance
      upon introduction of a hydroxyl group at the 5-position of Trp or indole was
      found to be due to a lowering of the (1)Lb transition energy. It was therefore
      believed that 5HW only features (1)Lb emission. Recently, calculations for 5
      hydroxyindole (5HI) in water revealed (1)La is the emitting state, and the same
      was predicted for 5HW incorporated in proteins. To clarify which state emits in
      5HI and 5HW, we present here excitation anisotropy spectra of these probes and of
      four proteins labeled with 5HW at a surface exposed position. Our data clearly
      show (1)Lb is the emitting state of 5HI, 5HW, and 5HW in three of the proteins
      investigated. For one protein mixed emission was observed, and the decay kinetics
      were found strongly dependent on the emission wavelength. This work provides the
      first experimental evidence that (1)La can be the emitting state for this Trp
      analogue incorporated in a protein.

PMID- 24020961
TI  - Isochromosome Yp and jumping translocation of Yq resulting in five cell lines in
      an infertile male: a case report and review of the literature.
AB  - BACKGROUND: Jumping translocations are a rare type of mosaicism in which the same
      portion of one donor chromosome is translocated to several recipient chromosomes.
      Constitutional forms of jumping translocations are rare, and the 48 cases
      reported to date have been associated with both normal and abnormal phenotypes.
      Concurrence of isochromosome (i) of one arm and translocation of the other is
      also rare, with seven reported cases. We describe a unique case involving
      concurrence of i(Yp) and a jumping translocation of Yq to the telomere of
      chromosomes 12q and 17q, which resulted in five cell lines. CASE PRESENTATION:
      The patient, an otherwise healthy 35-year-old man, was referred for cytogenetic
      studies because of absolute azoospermia. He had elevated levels of follicle
      stimulating hormone and luteinizing hormone, consistent with abnormal
      spermatogenesis, and decreased levels of free testosterone and inhibin B. G
      banded chromosome analysis revealed a mosaic male karyotype involving five
      abnormal cell lines. One of the cell lines showed loss of chromosome Y and
      presence of i(Yp) as the sole abnormality. Three cell lines exhibited jumping
      translocation: two involved 17qter, and the other involved 12qter as the
      recipient and Yq as the common donor chromosome. One of the cell lines with
      der(17) additionally showed i(Yp). The other der(17) and der(12) cell lines had a
      missing Y chromosome. All five cell lines were confirmed by FISH. Subtelomric
      FISH study demonstrated no loss of chromosome material from the recipient
      chromosomes at the translocation junctions. CONCLUSIONS: We postulate that a
      postzygotic pericentromeric break of the Y chromosome led to formation of
      isochromosome Yp, whereas Yq formed a jumping translocation through recombination
      between its internal telomere repeats and telomeric repeats of recipient
      chromosomes. This in turn led to either pairing or an exchange at the
      complimentary sequences. Such translocation junctions appear to be unstable and
      to result in a jumping translocation. Cryptic deletion or disruption of AZF
      (azoospermic factor) genes at Yq11 during translocation or defective pairing of X
      and Y chromosomes during meiosis, with abnormal sex vesicle formation and
      consequent spermatogenetic arrest, might be the main cause of the azoospermia in
      our patient.

PMID- 24020962
TI  - Comparison of breast and abdominal adipose tissue mesenchymal stromal/stem cells
      in support of proliferation of breast cancer cells.
AB  - In this study, we compared MSCs from breast and abdominal tissue in terms of
      their expression of genes deemed important in the support of breast cancer growth
      and their effect on gene profile of macrophages after coculture. In addition, we
      investigated the role of MSCs, alone or in combination with macrophages, on
      proliferation of breast cancer cell lines. Our results show that MSCs derived
      from breast and abdominal adipose tissues have a comparable gene expression
      profile, have similar effect on gene expression of macrophages, and are
      comparable in supporting breast cancer cell line proliferation. 

PMID- 24020963
TI  - Quantification of cervical spine muscle fat: a comparison between T1-weighted and
      multi-echo gradient echo imaging using a variable projection algorithm (VARPRO).
AB  - BACKGROUND: Previous data using T1-weighted MRI demonstrated neck muscle fat
      infiltration (MFI) in patients with poor functional recovery following whiplash.
      Such findings do not occur in those with milder symptoms of whiplash, chronic non
      traumatic neck pain or healthy controls, suggesting traumatic factors play a
      role. Muscle degeneration could potentially represent a quantifiable marker of
      poor recovery, but the temporal constraints of running a T1-weighted sequence and
      performing the subsequent analysis for muscle fat may be a barrier for clinical
      translation. The purpose of this preliminary study was to evaluate, quantify and
      compare MFI for the cervical multifidus muscles with T1-weighted imaging and a
      more rapid quantitative 3D multi-echo gradient echo (GRE) Dixon based method in
      healthy subjects. METHODS: 5 asymptomatic participants with no history of neck
      pain underwent cervical spine MRI with a Siemens 3 Tesla system. The muscle and
      fat signal intensities on axial spin-echo T1-weighted images were quantitatively
      classified for the cervical multifidii from C3-C7, bilaterally. Additional axial
      GRE Dixon based data for fat and water quantification were used for comparison
      via paired t-tests. Inter-tester reliability for fat and water measures with GRE
      images were examined using 1) Pearson's Intra-class correlation coefficient 2)
      Bland-Altman Plots and 3) Lin's-Concordance Coefficient. P < 0.05 was used to
      indicate significance. RESULTS: Total mean (SD) MFI (C3-C7) for the multifidii
      obtained with T1-weighted imaging and GRE were 18.4% (3.3) (range 14-22%) and
      18.8% (2.9) (range 15-22%), respectively. The Pearson correlation coefficients
      for inter-tester reliability on the GRE sequences for the C3-C7 multifidii ranged
      from .83 - .99, indicating high levels of agreement with segmental MFI measures.
      Bland-Altman Plots revealed all data points were within 2 SDs and concordance was
      established between 2-blinded raters, suggesting good agreement between two
      raters measuring fat and water with GRE imaging. CONCLUSIONS: Results of this
      preliminary study demonstrate reliability between 2 raters of varying experience
      for MRI analysis of MFI with 3D GRE MRI. The quantification of MFI for healthy
      cervical musculature is comparable to T1-weighted images. Inclusion of larger
      samples of symptomatic data and histological comparison with the reference
      standard biopsy is warranted.

PMID- 24020964
TI  - Using cytochrome b gene of mtDNA as a DNA barcoding marker in chicken strains.
AB  - This was the second study to apply using of a cytochrome b gene as barcoding tool
      in distinguishing among chicken strains. We performed polymerase chain reaction
      (PCR) amplification using universal primer to amplify around 415 bp fragment of
      cytochrome b gene of mtDNA. The tree reported that both Saudi chicken strains
      (black and dark brown) are closely related and it might be separated from same
      origin rather than bronze ones. The phylogenetic tree also, exploited that native
      chicken strains were closely related to cluster of Ceylon jungle fowl, black
      Minorca egg chicken and Fayoumi egg chicken. The genetic divergence between these
      populations or types of chickens in Saudi Arabia was low (0.02) and it was very
      low (0.011), when compared to other species of Gallus. We confirmed that short
      fragment of cyt-b gene as a universal DNA barcode region. It was much more
      accurate and efficient tool to discriminate inter-species than intra-species.
      Applying cyt-b of mtDNA was successfully distinguished among native strains and
      other species of Gallus as in a previous study. However, applying this thought on
      different species of farm animal species is recommended.

PMID- 24020965
TI  - Early classic hemofiltration exhibits no benefits in severe acute pancreatitis
      with early organ failure: a retrospective case-matched study.
AB  - Continuous venovenous hemofiltration (CVVH) is an important organ supportive
      technique. This study aimed to evaluate the impact of early classic CVVH on the
      outcomes of severe acute pancreatitis (SAP) patients with early organ failure
      (EOF). Between 2008 and 2012, a total of 44 SAP patients with EOF were admitted
      to our department. The 44 patients were classified into two groups according to
      whether they received early classic CVVH (2 L/h, initiated within 24 h after
      admission): 25 patients received early CVVH (ECVVH group), and 19 patients did
      not receive early CVVH (control group). The two groups were matched for age and
      Acute Physiology and Chronic Health Evaluation II scores. The severity of organ
      dysfunctions was evaluated by Sequential Organ Failure Assessment (SOFA) scores.
      Each group included 19 patients. The baseline characters between the two groups
      were balanced. The SOFA scores in the ECVVH group increased compared with those
      in the control group. The time to weaning from mechanical ventilation was
      significantly longer in the ECVVH group (log-rank test: chi(2)  = 4.007, P =
      0.045). Renal support was also significantly prolonged in the ECVVH group (the
      number of patients receiving CVVH 72 h after admission: 10 vs. 3, respectively, P
      = 0.038). Nine patients died in the ECVVH group versus six patients in the
      control group (P = 0.508). In conclusion, our study failed to prove that early
      classic CVVH had any benefits on the outcomes of SAP patients with EOF.
      Unexpectedly, early classic CVVH worsened organ functional capacity. However, it
      is possible that CVVH using advanced techniques may be beneficial in SAP patients
      with EOF. 

PMID- 24020967
TI  - Auriculotemporal neuralgia secondary to TMJ synovial cyst: a rare presentation of
      a rare entity.
AB  - Synovial cysts of the temporomandibular joint are rare, and to our knowledge,
      only 14 cases have been reported. The most common presentation is local pain and
      swelling. We present a case of a synovial cyst presenting with neuralgia in the
      distribution of the auriculotemporal nerve, initially misdiagnosed as trigeminal
      neuralgia. 

PMID- 24020966
TI  - Nonsteroidal selective androgen receptor modulators and selective estrogen
      receptor beta agonists moderate cognitive deficits and amyloid-beta levels in a
      mouse model of Alzheimer's disease.
AB  - Decreases of the sex steroids, testosterone and estrogen, are associated with
      increased risk of Alzheimer's disease. Testosterone and estrogen supplementation
      improves cognitive deficits in animal models of Alzheimer's disease. Sex hormones
      play a role in the regulation of amyloid-beta via induction of the amyloid-beta
      degrading enzymes neprilysin and insulin-degrading enzyme. To mimic the effect of
      dihydrotestosterone (DHT), we administered a selective androgen receptor agonist,
      ACP-105, alone and in combination with the selective estrogen receptor beta
      (ERbeta) agonist AC-186 to male gonadectomized triple transgenic mice. We
      assessed long-term spatial memory in the Morris water maze, spontaneous
      locomotion, and anxiety-like behavior in the open field and in the elevated plus
      maze. We found that ACP-105 given alone decreases anxiety-like behavior.
      Furthermore, when ACP-105 is administered in combination with AC-186, they
      increase the amyloid-beta degrading enzymes neprilysin and insulin-degrading
      enzyme and decrease amyloid-beta levels in the brain as well as improve
      cognition. Interestingly, the androgen receptor level in the brain was increased
      by chronic treatment with the same combination treatment, ACP-105 and AC-186, not
      seen with DHT or ACP-105 alone. Based on these results, the beneficial effect of
      the selective ERbeta agonist as a potential therapeutic for Alzheimer's disease
      warrants further investigation. 

PMID- 24020968
TI  - TNF receptor-associated factor 5 gene confers genetic predisposition to acute
      anterior uveitis and pediatric uveitis.
AB  - INTRODUCTION: TNF Receptor-Associated Factor 5 (TRAF5) has been shown to be
      associated with autoimmune disease. The current study sought to investigate the
      potential association of TRAF5 with acute anterior uveitis (AAU) and pediatric
      uveitis in Han Chinese. METHODS: Three TRAF5 SNPs were analyzed in 450 AAU
      patients with or without ankylosing spondylitis (AS), 458 pediatric uveitis
      patients, and 1,601 healthy controls by using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) or TaqMan SNP Genotyping
      Assay. Numerous variables were evaluated, including age, sex distribution, and
      clinical and laboratory observations. RESULTS: Two SNPs (rs6540679, rs12569232)
      of TRAF5 were associated with pediatric uveitis, and rs12569232 also showed a
      relation with the presence of microvascular leakage. No significant associations
      were found when patients were subdivided according to their rheumatoid factor
      (RF) or anti-nuclear antibody (ANA) status or whether they had juvenile
      idiopathic arthritis (JIA). Rs12569232 predisposed to AAU and its subgroups (with
      ankylosing spondylitis (AS) or HLA-B27 positive). No association was found
      between rs10863888 and either pediatric uveitis or AAU. CONCLUSION: This study
      revealed that TRAF5 is involved in the development of AAU and pediatric uveitis.
      Further stratified analysis according to the clinical and laboratory observations
      suggested that rs12569232/TRAF5 may play a role in the development of retinal
      vasculitis.

PMID- 24020969
TI  - NMR-based conformational ensembles explain pH-gated opening and closing of OmpG
      channel.
AB  - The outer membrane protein G (OmpG) is a monomeric 33 kDa 14-stranded beta-barrel
      membrane protein functioning as a nonspecific porin for the uptake of
      oligosaccharides in Escherichia coli. Two different crystal structures of OmpG
      obtained at different values of pH suggest a pH-gated pore opening mechanism. In
      these structures, extracellular loop 6 extends away from the barrel wall at
      neutral pH but is folded back into the pore lumen at low pH, blocking transport
      through the pore. Loop 6 was invisible in a previously published solution NMR
      structure of OmpG in n-dodecylphosphocholine micelles, presumably due to
      conformational exchange on an intermediate NMR time scale. Here we present an NMR
      paramagnetic relaxation enhancement (PRE)-based approach to visualize the
      conformational dynamics of loop 6 and to calculate conformational ensembles that
      explain the pH-gated opening and closing of the OmpG channel. The different loop
      conformers detected by the PRE ensemble calculations were validated by disulfide
      cross-linking of strategically engineered cysteines and electrophysiological
      single channel recordings. The results indicate a more dynamically regulated
      channel opening and closing than previously thought and reveal additional
      membrane-associated conformational ensembles at pH 6.3 and 7.0. We anticipate
      this approach to be generally applicable to detect and characterize functionally
      important conformational ensembles of membrane proteins. 

PMID- 24020970
TI  - Subnanowatt carbon nanotube complementary logic enabled by threshold voltage
      control.
AB  - In this Letter, we demonstrate thin-film single-walled carbon nanotube (SWCNT)
      complementary metal-oxide-semiconductor (CMOS) logic devices with subnanowatt
      static power consumption and full rail-to-rail voltage transfer characteristics
      as is required for logic gate cascading. These results are enabled by a local
      metal gate structure that achieves enhancement-mode p-type and n-type SWCNT thin
      film transistors (TFTs) with widely separated and symmetric threshold voltages.
      These complementary SWCNT TFTs are integrated to demonstrate CMOS inverter, NAND,
      and NOR logic gates at supply voltages as low as 0.8 V with ideal rail-to-rail
      operation, subnanowatt static power consumption, high gain, and excellent noise
      immunity. This work provides a direct pathway for solution processable, large
      area, power efficient SWCNT advanced logic circuits and systems. 

PMID- 24020972
TI  - Oxycodone/naloxone in the management of patients with pain and opioid-induced
      bowel dysfunction.
AB  - INTRODUCTION: Common opioids adverse effects include opioid-induced bowel
      dysfunction (OIBD), which comprises opioid-induced constipation, dry mouth,
      nausea, vomiting, gastric stasis, bloating, and abdominal pain. Traditional
      laxatives which are often prescribed for the prevention and treatment of OIBD
      possess limited efficacy and display adverse effects. A targeted approach to OIBD
      management is the use of a combination of an opioid agonist with opioid receptor
      antagonist or administration of purely peripherally acting opioid receptor
      antagonists. METHODS: A literature search with terms "oxycodone/naloxone" in the
      PubMed and MEDLINE database updated on 31(st) July 2013. All studies of
      oxycodone/naloxone (randomized, controlled trials and open, uncontrolled studies)
      were included. In addition, studies on pharmacokinetics and pharmacodynamics of
      oxycodone/naloxone were included. RESULTS: A combination of prolonged-release
      oxycodone with prolonged-release naloxone (OXN) in one tablet with a fixed 2:1
      ratio provides effective analgesia with limited disturbing effect on bowel
      function. Oxycodone is a valued opioid administered either as the first strong
      opioid or when other strong opioids have been ineffective. Naloxone is an opioid
      receptor antagonist that displays local antagonist effect on opioid receptors in
      the gastrointestinal tract and is nearly completely inactivated in the liver
      after oral administration. As demonstrated in controlled studies conducted in
      patients with chronic non-malignant and cancer-related pain OXN in daily doses up
      to 80 mg/40 mg provided equally effective analgesia with an improved bowel
      function compared to oxycodone administered alone. CONCLUSION: OXN is an
      important drug for chronic pain management, prevention and treatment of OIBD.

PMID- 24020971
TI  - Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a
      cohort study.
AB  - OBJECTIVE: To determine whether outpatient exposure to calcium-channel blockers
      (CCBs) at the time of delivery is associated with an increased risk for
      postpartum haemorrhage (PPH). DESIGN: Cohort study. SETTING: United States of
      America. POPULATION OR SAMPLE: Medicaid beneficiaries. METHODS: We identified a
      cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or
      labetalol for pre-existing or gestational hypertension whose days of supply
      overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared
      in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity
      score matching and stratification were used to address potential confounding.
      MAIN OUTCOME MEASURES: The occurrence of PPH during the delivery hospitalisation.
      RESULTS: There were 27 patients exposed to CCBs (2.2%) and 232 patients exposed
      to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for
      confounders, there was no meaningful association between CCB exposure and PPH in
      the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified
      (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained
      across multiple sensitivity analyses. CONCLUSIONS: The outpatient use of CCBs in
      late pregnancy for the treatment of hypertension does not increase the risk of
      PPH.

PMID- 24020973
TI  - The monoaminergic tripartite synapse: a putative target for currently available
      antidepressant drugs.
AB  - Antidepressant drugs such as the serotonin (5-HT)/norepinephrine (NE) and
      dopamine (DA) reuptake inhibitors activate monoaminergic neurotransmission in
      various brain regions, such as the amygdala, the frontal cortex or the
      hippocampus. Although this property is well established, the post-synaptic
      mechanisms by which these pharmacological agents exert therapeutic activity in
      major depressive disorders (MDD) is not fully understood. Recent clinical and
      preclinical studies have indicated that the density and reactivity of glia and
      more particularly of astrocytes are reduced in MDD patients. These data along
      with the fact that astrocytes express monoaminergic transporters and receptors
      make these cells putative targets for antidepressant treatments. Accordingly, in
      vitro evidence has demonstrated that the application of various classes of
      antidepressant drugs on rodent primary astrocyte cultures elicits a wide spectrum
      of responses, from the rise in cytosolic calcium concentrations, as a marker of
      cellular activity, to the release of glucose metabolites, gliotransmitters and
      neurotrophic factors. Remarkably, antidepressant drugs also attenuate the release
      of inflammatory molecules from reactive astrocytes or microglia, suggesting that
      part of the beneficial effects in depressed patients or animal models of
      depression might result from the ability of antidepressants to regulate the
      synthesis and release of psychoactive substances acting on both pre- and post
      synaptic neurons. Among the many long-term targets of antidepressant drugs,
      brainderived neurotrophic factor (BDNF) has been well studied because of the
      positive influence on adult hippocampal neurogenesis, synaptogenesis and the
      local serotonergic tone. This review will illustrate how the concept of the
      tripartite synapse, which is classically associated with different forms of
      plasticity involving glutamate, could be expanded to the monoaminergic systems to
      regulate antidepressant drug responses. The recent in vivo data supporting that
      hippocampal astrocytes act in concert with neurons to release BDNF under
      pharmacological conditions and thereby regulate different facets of anxiolytic
      /antidepressant-like activities through neurogenesis-dependent and independent
      mechanisms will be emphasized. 

PMID- 24020975
TI  - Biomarkers for early detection of non-alcoholic steatohepatitis: implications for
      drug development and clinical trials.
AB  - The term non-alcoholic fatty liver disease (NAFLD) comprises at least four
      pathological entities (definite nonalcoholic steatohepatitis [NASH], borderline
      "zone 3" pattern, borderline "zone 1" pattern, not steatohepatitis with
      steatosis) with distinct patterns of lipid storage, fibrosis, and hepatocyte
      injury. Recent pathophysiological advances hold promise to provide much needed
      surrogate non-invasive biomarkers to detect steatohepatitis, fibrosis, and
      monitor NASH progression (or resolution, in the setting of clinical trials)
      without the cumbersome use of liver biopsy. Herein, we reviewed the current
      status of multimodal biomarker candidates derived from biochemical and genetic
      studies of NASH, as well as potential markers derived from imaging studies. A
      literature search was conducted in March 2013 on PubMed, Ovid Embase, Ovid
      Medline and Scopus using the following search terms: steatosis, non-alcoholic
      steatohepatitis, biomarker, genetics, imaging, clinical trials. Rather than to
      biopsy, the identification of steatohepatitis and fibrosis may originate
      primarily from prespecified multimodal biomarker data, including positive
      findings on serum or genetic biomarkers, and imaging tests like MR elastography
      or Fibroscan. In the setting of clinical trials, it seems recommendable to widen
      and expand the therapeutic vision beyond insulin resistance and focus on trials
      in very early NASH stages. The paradigm shift towards an earlier noninvasive
      characterization and diagnosis of NASH and fibrosis will be crucial to redefine
      and establish successful interventional trials. 

PMID- 24020974
TI  - Acute and chronic stress-induced disturbances of microglial plasticity, phenotype
      and function.
AB  - Traditionally, microglia have been considered to act as macrophages of the
      central nervous system. While this concept still remains true it is also becoming
      increasingly apparent that microglia are involved in a host of nonimmunological
      activities, such as monitoring synaptic function and maintaining synaptic
      integrity. It has also become apparent that microglia are exquisitely sensitive
      to perturbation by environmental challenges. The aim of the current review is to
      critically examine the now substantial literature that has developed around the
      ability of acute, sub-chronic and chronic stressors to alter microglial structure
      and function. The vast majority of studies have demonstrated that stress promotes
      significant structural remodelling of microglia, and can enhance the release of
      pro-inflammatory cytokines from microglia. Mechanistically, many of these effects
      appear to be driven by traditional stress-linked signalling molecules, namely
      corticosterone and norepinephrine. The specific effects of these signalling
      molecules are, however, complex as they can exert both inhibitory and suppressive
      effects on microglia depending upon the duration and intensity of exposure.
      Importantly, research has now shown that these stress-induced microglial
      alterations, rather than being epiphenomena, have broader behavioural
      implications, with the available evidence implicating microglia in directly
      regulating certain aspects of cognitive function and emotional regulation. 

PMID- 24020976
TI  - Glia: an important target for anti-inflammatory and antidepressant activity.
AB  - Activated glial cells are capable of generating various inflammatory mediators,
      including cytokines, nitric oxide and reactive oxygen species. These potentially
      neurotoxic molecules have been suggested to play a role in the etiology and
      development of depression. Accumulating evidence indicates that antidepressants
      have inhibitory effects on inflammatory activation of glial cells and confer
      neuroprotection under neuropathological conditions. Such efficacy of
      antidepressants appears to depend on suppressing microglial production of
      inflammatory substances and up-regulating both astrocytic secretion of
      neurotrophins and astrocytic glutamine synthase, which converts neurotoxic
      glutamate into non-toxic glutamine. Therefore, glial cells, both as source and
      target of inflammatory molecules, may represent a potential promising target
      involved in the pathophysiology of depression. Moreover, antidepressants have the
      possibility to be useful treatment, not only for depression, but for a broad
      spectrum of neuroinflammatory and neurodegenerative disorders where the
      pathogenesis is associated with glial activation. 

PMID- 24020977
TI  - Lentiviral vectors: a powerful tool to target astrocytes in vivo.
AB  - The morphological and functional diversity of astrocytes, and their essential
      contribution in physiological and pathological conditions, are starting to
      emerge. However, experimental systems to investigate neuron-glia interactions and
      develop innovative approaches for the treatment of central nervous system (CNS)
      disorders are still very limited. Fluorescent reporter genes have been used to
      visualize populations of astrocytes and produce an atlas of gene expression in
      the brain. Knock-down or knock-out of astrocytic proteins using transgenesis have
      also been developed, but these techniques remain complex and time-consuming.
      Viral vectors have been developed to overexpress or silence genes of interest as
      they can be used for both in vitro and in vivo studies in adult mammalian
      species. In most cases, high transduction efficiency and long-term transgene
      expression are observed in neurons but there is limited expression in astrocytes.
      Several strategies have been developed to shift the tropism of lentiviral vectors
      (LV) and allow local and controlled gene expression in glial cells. In this
      review, we describe how modifications of the interaction between the LV envelope
      glycoprotein and the surface receptor molecules on target cells, or the
      integration of cell-specific promoters and miRNA post-transcriptional regulatory
      elements have been used to selectively express transgenes in astrocytes. 

PMID- 24020979
TI  - Change in retinal blood flow and retinal arterial diameter after intraocular
      pressure reduction in glaucomatous eyes.
AB  - PURPOSE: To study retinal blood flow and vessel diameter after intra-ocular
      pressure (IOP) reduction in high- and low-pressure glaucomas, that is,
      exfoliation glaucoma (ExG) and normal-tension glaucoma (NTG). METHODS: The study
      included 17 eyes with ExG and 20 with NTG. A minimum of 25% IOP reduction was
      achieved by deep sclerectomy. Blood flow in the temporal peripapillary retina was
      measured with scanning laser Doppler flowmetry (Heidelberg Retina Flowmeter,
      HRF), and retinal vessel diameters were evaluated with the retinal vessel
      analyser (RVA). Examinations were carried out before and 3 months after the
      operation. RESULTS: Pre-operative IOP was significantly higher in ExG than in NTG
      (median 26 mmHg, range 20-33 mmHg versus 15 mmHg, 12-20; p < 0.001). Surgery
      reduced IOP significantly both in ExG eyes (postoperative IOP 13 mmHg, 5-17; p <
      0.001) and NTG eyes (9 mmHg, 3-13; p < 0.001). After the operation, systolic
      retinal flow was significantly reduced in ExG eyes, whereas in NTG, HRF
      parameters remained unchanged. Pre-operatively, the central retinal artery
      equivalent (CRAE) and arteriovenous ratio (AVR) were higher in ExG than in NTG
      eyes. After IOP reduction, both CRAE and AVR were reduced in ExG eyes, but
      remained unchanged in NTG. CONCLUSION: The study showed that before IOP
      reduction, arterial diameter was larger in ExG eyes than in NTG eyes. IOP
      reduction resulted in vasoconstriction and reduction of flow in ExG, whereas in
      NTG, both vessel diameter and retinal flow remained unchanged.

PMID- 24020978
TI  - Attitudes and perceptions of nephrology nurses towards dialysis modality
      selection: a survey study.
AB  - BACKGROUND: There is a paucity of information about the views of dialysis nurses
      towards dialysis modality selection, yet nurses often have the most direct
      contact time with patients. We conducted a survey to better understand nurses'
      attitudes and perceptions, and hypothesized that nurses with different areas of
      expertise would have differences in opinions. METHODS: We administered an
      electronic survey to all dialysis/predialysis nurses (n = 129) at a large,
      tertiary care center. The survey included questions about preferred therapy - in
      center hemodialysis (CHD), versus home dialysis (home hemodialysis and peritoneal
      dialysis) and ideal modality mix. Responses were compared between nurses with
      home dialysis and CHD experience. RESULTS: The survey response rate was 69%. Both
      nursing groups ranked patient caregivers and dialysis nurses as having the least
      impact on patient modality selection. For most patient characteristics (including
      age > 70 years and presence of multiple chronic illnesses), CHD nurses felt that
      CHD was somewhat or strongly preferred, while home dialysis nurses preferred a
      home modality (p < 0.001 for all characteristics studied). Similar differences in
      responses were noted for patient/system factors such as patient survival, cost to
      patients and nursing job security. Compared to CHD nurses, a higher proportion of
      home dialysis nurses felt that CHD was over-utilized (85% versus 58%, p = 0.024).
      CONCLUSION: Dialysis nurses have prevailing views about modality selection that
      are strongly determined by their area of experience and expertise.

PMID- 24020980
TI  - Adeno-associated virus enhances wild-type and oncolytic adenovirus spread.
AB  - The contamination of adenovirus (Ad) stocks with adeno-associated viruses (AAV)
      is usually unnoticed, and it has been associated with lower Ad yields upon large
      scale production. During Ad propagation, AAV contamination needs to be detected
      routinely by polymerase chain reaction without symptomatic suspicion. In this
      study, we describe that the coinfection of either Ad wild type 5 or oncolytic Ad
      with AAV results in a large-plaque phenotype associated with an accelerated
      release of Ad from coinfected cells. This accelerated release was accompanied
      with the expected decrease in Ad yields in two out of three cell lines tested.
      Despite this lower Ad yield, coinfection with AAV accelerated cell death and
      enhanced the cytotoxicity mediated by Ad propagation. Intratumoral coinjection of
      Ad and AAV in two xenograft tumor models improved antitumor activity and mouse
      survival. Therefore, we conclude that accidental or intentional AAV coinfection
      has important implications for Ad-mediated virotherapy.

PMID- 24020981
TI  - Aortopulmonary window: a rare mechanism of inter-circulatory mixing and prepared
      left ventricle in transposition of the great arteries with intact ventricular
      septum.
AB  - Transposition of the great arteries with intact ventricular septum and
      aortopulmonary window is an extremely rare anatomic combination associated with
      high morbidity and mortality. We report a case of a 3-month-old baby with d
      transposition of the great arteries with intact ventricular septum and a large
      aortopulmonary window as a mechanism of inter-circulatory mixing. 

PMID- 24020982
TI  - Talking about links between sexually transmitted infections and infertility with
      college and university students from SE England, UK: a qualitative study.
AB  - BACKGROUND: Sexually transmitted infections (STIs) such as chlamydia and
      gonorrhoea are largely symptomless diseases which, left untreated, can result in
      serious complications including infertility. Fertility problems currently affect
      approximately one in seven couples in the UK and there is increasing demand for
      couples seeking reproductive technologies. Young people are at greatest risk of
      contracting STIs, therefore this study aimed to identify young people's knowledge
      and beliefs about the link between untreated STIs and infertility. METHODS: Focus
      groups were conducted with participants aged 16-24 years old inclusive in college
      or university settings in the SE of England. Groups were quota sampled on the
      basis of age and gender. A topic guide was used. The data were analysed using a
      framework analysis approach. RESULTS: Ten single-sex focus groups were conducted
      with sixty participants: six groups of college students and four groups of
      university students. Participants were generally aware of the link between STIs
      and potential infertility and considered the discussion of this subject very
      relevant at their age. Knowledge about how and why STIs potentially lead to
      fertility complications was poor. The issues of blame relating to infertility
      following an STI emerged, although most participants did not think that access to
      free reproductive technologies after an untreated STI should be limited.
      CONCLUSIONS: Young people would benefit from more education in order to improve
      their understanding of the long-term consequences of untreated STIs, such as
      infertility. Participants in our sample felt these were extremely relevant and
      important issues for them to understand alongside current education about STIs.

PMID- 24020983
TI  - In vivo passive sampling of nonpolar contaminants in brown trout (Salmo trutta).
AB  - Equilibrium passive sampling through in vivo implantation can help circumvent
      complex extractions of biological tissues, provide more accurate information on
      chemical contaminant burden based on the fugacity of a chemical in an organism
      rather than conventional normalization to lipid content, and improve the
      assessment of contaminant bioaccumulation potential. Here, we explored the
      feasibility of in vivo implantation for the passive sampling of neutral
      hydrophobic contaminants through the insertion of a silicone tag into brown trout
      (Salmo trutta). Implanted fish from the upper reaches of the River Alna (Oslo,
      Norway) were relocated to a polluted section of the river for a 28 day caged
      exposure. "Whole fish" lipid-silicone distribution coefficients (Dlip-sil) were
      calculated for chlorinated compounds measured in whole fish and in silicone tags
      of 13 fish. Dlip-sil ranged from 13.6 to 40.0 g g(-1) for polychlorinated
      biphenyl congeners 28-156 (CB28 and CB156), respectively, and are in close
      agreement with literature in vitro lipid phase and tissue-based lipid-silicone
      partition coefficients. After dissection a further of eight fish, muscle and
      liver samples were analyzed separately. Muscle-based Dlip-sil values similar to
      the whole fish data were observed. However, lipid-normalized concentrations in
      the liver tended to be lower than in muscle for most compounds (by up to 50%).
      Values of whole fish Dlip-sil for brominated diphenyl ethers determined for three
      fish were in the range of 8.6-51 g g(-1) and in agreement with chlorinated
      substances. Finally, fugacity ratios calculated from equilibrium concentrations
      in fish-implanted and water-exposed silicone provided information on the
      bioaccumulation for chlorinated compounds as well as for some polycyclic aromatic
      hydrocarbons. Equilibrium passive sampling through in vivo implantation can allow
      the comparison of a chemical's activity or fugacity in biotic as well as abiotic
      environmental compartments and at different trophic levels up to humans. 

PMID- 24020984
TI  - Breath control during a tiptoe task.
AB  - Examination of naturally occurring respiration during postural challenges may
      increase our understanding of the factors linking respiration to lumbar segmental
      control. This study determined if the timing and magnitude of inhaled volume
      changes were related to mechanical events that challenge spinal stability during
      a tiptoe task. Thirty healthy individuals (15 male) had airflow recorded while
      they completed a tiptoe task which involved: moving onto tiptoe while reaching
      toward a hanging target (ascent); grasping and holding the target while
      maintaining the tiptoe position for 3 s (hold); and then returning to the start
      position (descent). The rate of airflow and amount of inhaled volume (normalized
      to vital capacity (%VC)) were identified at 13 different intervals spanning the
      ascent, hold and descent phase. Using repeated measures analysis of variance,
      significant main effects were identified for both rate of airflow (p < 0.001) and
      %VC (p < 0.001). Exploration of these main effects revealed that individuals
      tended to inspire and increase %VC during the ascent phase, hold their breath and
      maintain %VC during the hold phase when whole body balance is challenged, and
      exhale during the descent phase. These findings are congruent with theories
      suggesting that breath control is linked in predictable ways to potentially
      improve lumbar spine stiffness when presented with mechanical challenges during
      functional tasks.

PMID- 24020985
TI  - Reliability and concurrent criterion validity of a novel technique for analyzing
      hip kinematics during running.
AB  - Excessive frontal plane hip kinematics during running has been associated with
      numerous running pathologies. Traditionally, assessment of hip kinematics during
      running required expensive and complex equipment and procedures making objective
      running assessment difficult for practicing clinicians. The aim of this study was
      to establish the reliability and validity of a novel technique designed for
      clinicians that allows for objective assessment of frontal plane hip kinematics
      during running. Hip angles and excursions were measured using videos and jpeg
      images of 10 subjects (five males and five females) running. A 2-D motion
      analysis system and computer algorithm served as reference measures. Six raters
      (three licensed physical therapists and three student physical therapists) took
      measures on two instances. Reliability was examined using intraclass correlation
      coefficients (ICC). Validity was investigated with ICCs, 95% limits of agreement
      (LA), and mean absolute differences (MAD) by comparing each rater's 2-trial
      average to the criterion reference values. The ICCs for interrater and intrarater
      reliability for angle and excursion measures ranged from 0.82 to 0.99. The
      validity ICCs of all measures ranged from 0.89 to 0.99 with acceptable LA. The
      MAD ranged from 0.5 degrees -1.5 degrees . These results indicate that this novel
      technique is reliable and valid for measuring hip kinematics compared to the
      reference measures making it suitable for broad-based clinical use.

PMID- 24020989
TI  - Using value of information to guide evaluation of decision supports for
      differential diagnosis: is it time for a new look?
AB  - BACKGROUND: Decision support systems for differential diagnosis have
      traditionally been evaluated on the basis of criteria how sensitively and
      specifically they are able to identify the correct diagnosis established by
      expert clinicians. DISCUSSION: This article questions whether evaluation criteria
      pertaining to identifying the correct diagnosis are most appropriate or useful.
      Instead it advocates evaluation of decision support systems for differential
      diagnosis based on the criterion of maximizing value of information. SUMMARY:
      This approach quantitatively and systematically integrates several important
      clinical management priorities, including avoiding serious diagnostic errors of
      omission and avoiding harmful or expensive tests.

PMID- 24020990
TI  - Novel hepatitis B virus strain developing due to recombination between genotypes
      H and B strains isolated from a Japanese patient.
AB  - AIM: In Japan, genotypes B and C are the predominant genotypes isolated from
      patients with chronic hepatitis B, while genotype A predominates in patients with
      acute hepatitis B. Globalization, however, appears to have changed the
      distribution of the hepatitis B virus (HBV) genotypes. Thus, the viral
      characteristics of HBV genotypes other than genotypes A, B and C were examined.
      METHODS: Screening of genotypes was performed by enzyme immunoassay and/or
      polymerase chain reaction INVADER method in 222 patients with HBV. The full
      length nucleotide sequences of unusual strains were compared to those in the
      database, followed by construction of a phylogenetic tree. RESULTS: Unusual HBV
      strains were isolated from two patients: a 27-year-old Japanese bisexual man with
      acute hepatitis B with HIV co-infection and a 52-year-old Japanese man with
      chronic hepatitis B. The former strain was classified as genotype H, showing an
      overall identity of 99.8% to the Thailand strain (EU498228), while the nucleotide
      sequence of the latter strain showed similarity to the genotype B strains
      isolated in Malaysia (JQ027316) and Indonesia (JQ429079) between DR2 and DR1 in
      the X region, with identities of 96.9%. However, this strain was classified as
      genotype H by full-length sequence analysis, and the sequence between nt2023 and
      nt2262 showed no similarity to that in any previously reported strains.
      CONCLUSION: HBV strains showing recombination between genotype B and H strains
      were found even in chronic hepatitis patients in Japan. Globalization may yield
      HBV strains of possible novel genotypes containing novel nucleotide sequences in
      the precore/core region.

PMID- 24020991
TI  - Metabolic interaction between cancer cells and stromal cells according to breast
      cancer molecular subtype.
AB  - INTRODUCTION: The aim of this study was to investigate the differential
      expression of markers related to metabolic, mitochondrial and autophagy status in
      different molecular subtypes of breast cancer. METHODS: Using tissue microarray
      sections generated from 740 cases of breast cancer, we performed
      immunohistochemical staining for Glut-1, CAIX, MCT4, ATP synthase, glutaminase,
      BNIP3, Beclin-1, LC3A, LC3B and p62. Based on the immunohistochemical expression
      of estrogen receptor (ER), progesterone (PR), HER2, and Ki-67 labeling index, the
      cases were classified into luminal A, luminal B, HER2 and triple-negative breast
      cancer (TNBC). We further classified metabolic phenotypes of tumors according to
      glycolytic status by assessing Glut-1 and CAIX expression as follows: Warburg
      type: tumor (glycolysis type), stroma (nonglycolysis type); reverse Warburg type:
      tumor (nonglycolysis type), stroma (glycolysis type); mixed type: tumor
      (glycolysis type), stroma (glycolysis type); and null type: tumor (nonglycolysis
      type), stroma (nonglycolysis type). RESULTS: Expression of Glut-1, MCT4 and LC3A
      was highest in TNBC and lowest in luminal A type (P < 0.001). Tumors were
      classified into 298 Warburg type (40.3%), 54 reverse Warburg type (7.3%), 62
      mixed type (8.4%) and 326 null type (44.0%). The mixed type had a higher
      histologic grade, ER negativity, PR negativity and Ki-67 index, whereas the null
      type showed lower histologic grade, ER positivity, PR positivity and Ki-67 index
      (P < 0.001). TNBC constituted the major portion of Warburg and mixed types, and
      luminal A consisted mainly of reverse Warburg and null types (P < 0.001).
      CONCLUSION: Breast cancer is heterogeneous in its metabolic status, and therefore
      it can be classified into various metabolic phenotypes. Specifically, the Warburg
      and mixed types had strong associations with TNBC, whereas reverse the Warburg
      and null types had associations with the luminal type, suggesting a correlation
      between metabolic phenotype and the biology of breast cancer.

PMID- 24020992
TI  - Secretory factors from rat adipose tissue explants promote adipogenesis and
      angiogenesis.
AB  - Adipogenic differentiation of adipose-derived stem cells (ASCs) is known to be
      affected by many promoting and inhibiting factors, and correlated with
      surrounding cells and extracellular matrix. However, few studies have evaluated
      the effect of secreted biological molecules from adipose tissue explants on the
      growth of ASCs. In this study, ASCs were isolated and the secretory factors from
      adipose tissue explants (SFAE) were prepared from adipose tissue explants. The
      multilineage differentiation potential of ASCs was determined using different
      inductive media. The influence of SFAE on the colony formation and proliferation
      of ASCs was determined using colony-forming efficiency assay and Cell Counting
      Kit-8 assay, respectively. Real-time polymerase chain reaction and Western blot
      were performed to analyze the beneficial effect of SFAE on the adipogenesis and
      angiogenesis of ASCs. Utilizing gelatin scaffold, the influence of SFAE on ASCs
      was investigated in vivo. Subsequently, cell/gelatin constructs were cultured in
      a subcutaneous pocket on a rat dorsum for 2 and 9 weeks, and the resultant
      samples were histologically evaluated. Results showed that ASCs derived from
      adipose explants can differentiate along multiple lineages in vitro. Utilizing
      SFAE, the proliferation and colony-forming efficiency of ASCs were inhibited,
      while the expression of adipogenesis markers such as C/EBPbeta, PPARgamma2, and
      LPL, as well as angiogenesis factor VEGF-A were promoted. Moreover, the
      beneficial effect of SFAE on adipogenesis was revealed in vivo. In conclusion,
      our results suggested that SFAE has beneficial influence on adipogenesis and
      angiogenesis both in vitro and in vivo. 

PMID- 24020993
TI  - gff2sequence, a new user friendly tool for the generation of genomic sequences.
AB  - BACKGROUND: General Feature Format (GFF) files are used to store genome features
      such as genes, exons, introns, primary transcripts etc. Although many software
      packages (i.e. ab initio gene prediction programs) can annotate features by using
      such a standard, a small number of tools have been developed to extract the
      corresponding sequence information from the original genome. However the present
      tools do not execute either a quality control or a customizable filter of the
      annotated features is available. FINDINGS: gff2sequence is a program that
      extracts nucleotide/protein sequences from a genomic multifasta by using the
      information provided by a general feature format file. While a graphical user
      interface makes this software very easy to use, a C++ algorithm allows high
      performance together with low hardware demand. The software also allows the
      extraction of the genic portions such as the untranslated and the coding
      sequences. Moreover a highly customizable quality control pipeline can be used to
      deal with anomalous splicing sites, incorrect open reading frames and not
      canonical characters within the retrieved sequences. CONCLUSIONS: gff2sequence is
      a user friendly program that allows the generation of highly customizable
      sequence datasets by processing a general feature format file. The presence of a
      wide range of quality filters makes this tool also suitable for refining the ab
      initio gene predictions.

PMID- 24020994
TI  - Treatment of chronic migraine: a 3-month comparator study of naproxen sodium vs
      SumaRT/Nap.
AB  - OBJECTIVE: To compare the use of a combination of 85 mg sumatriptan plus 500 mg
      naproxen sodium in a combination tablet with 500 mg naproxen sodium in an
      identically appearing tablet when used as a daily preventative and acute
      treatment for 1 month and episodic acute treatment for an additional 2 months in
      patients with chronic migraine. BACKGROUND: To date, there has been minimal study
      of acute medications for patients with chronic migraine. Consequently, there is a
      paucity of study methodology or evidence-based guidance on the use of acute
      treatment medications in patients with chronic migraine. METHODS: This two
      center, double-blind, randomized, parallel-group, comparator pilot trial of 28
      subjects, 18 to 65 years of age, with ICHD-II defined chronic migraine, was
      designed to generate hypotheses about the efficacy of 2 established acute
      migraine medications used both as a daily preventive treatment (month 1) and
      episodic acute treatment (months 1, 2, and 3). Subjects were randomized 1:1 to
      treat daily with SumaRT/Nap (85 mg sumatriptan + 500 mg naproxen sodium) (group
      A) or naproxen sodium (500 mg) (group B) in a prophylactic strategy for 1 month
      followed by 2 months of the same medications used for episodic acute treatment.
      RESULTS: The combination of SumaRT/Nap used over a 3-month period did not appear
      to significantly reduce the number of migraine headache days. In the subset of
      subjects using naproxen sodium and completing the study per protocol, there was a
      marked reduction in migraine headache days (P < .02 vs 0.25, respectively).
      Duration of migraine from treatment to pain free decreased in both groups, but
      was more robust in group B from baseline to month 3. Subjects in group B
      completing the study per protocol reported a 56% reduction in headache days vs 8%
      for group A. Subjects in group A and group B completing the study per protocol
      had considerably better 2-hour headache relief than subjects withdrawing early
      from the study. More subjects in group B prematurely withdrew from the study
      because of lack of efficacy (5 vs 1, respectively). Despite using significant
      quantities of acute medication during month 1, there was a reduction of acute
      medication in month 2 and 3 vs baseline vs month 1, particularly in the naproxen
      group. CONCLUSION: A combination of SumaRT/Nap (group A) did not appear to reduce
      migraine headache frequency over a 3-month period. Subjects using naproxen sodium
      (group B) alone and completing the study per protocol had a marked statistically
      significant reduction in migraine headache days. Both groups completing the study
      per protocol had experienced clinically meaningful 2-hour headache relief. This
      suggests there may be a subset of patients with chronic migraine that are
      responsive to high doses of naproxen as an acute intervention with a significant
      prophylactic benefit. Subjects randomized to SumaRT/Nap experience benefit,
      primarily as an acute intervention. This hypothesis may warrant future larger
      scale clinical trials. Frequent dosing of SumaRT/Nap or naproxen sodium was well
      tolerated in this study.

PMID- 24020995
TI  - The mitochondrial genome of the scallop Mimachlamys senatoria (Bivalvia,
      Pectinidae).
AB  - The mitochondrial (mt) genome of the scallop Mimachlamys senatoria (17,383 bp),
      an economically and ecologically important bivalve, was newly sequenced and
      annotated. Comparative analyses between M. senatoria and its congeneric sister
      species M. nobilis revealed three new findings: (1) M. senatoria is more prone to
      use G-rich start/stop codon, and variation in start/stop codon usage is species
      correlated rather than gene-correlated, and in some extent, bears useful
      phylogenetic information; (2) The A + T content is unexpectedly low (54.1%) in
      MNR and that is unexpectedly high (65.4%) in atp8 in both congeneric scallops,
      which may represent a novel evolutionary pattern of mt genomic nucleotide
      composition; and (3) The tRNA gene cluster "NGV" locating upstream of the nad1 in
      M. senatoria is replaced by "NTGV" in M. nobilis, and a parsimonious explanation
      for the existence of trnT in M. nobilis is that this gene was derived from a
      recently duplicated trnG gene via an alloacceptor tRNA gene recruitment process.

PMID- 24020996
TI  - The complete mitochondrial genome of Spinibarbus sinensis (Bleeker).
AB  - The mitogenome of Spinibarbus sinensis was 16,591 bp long containing two rRNA, 22
      tRNA, 13 protein-coding genes and one D-loop region. Eight tRNA genes and one
      protein-coding gene were encoded on light strand, the others on heavy strand. The
      base composition and gene arrangement of S. sinensis mitogenome was identical to
      typical vertebrate.

PMID- 24020997
TI  - Genetic characterization of Golden mahseer (Tor putitora) populations using
      mitochondrial DNA markers.
AB  - Golden Mahseer (Tor putitora) is an economically important fish of India and
      Southeast Asia. The present study examined the genetic variations between seven
      geographically isolated populations of T. putitora using Cyt b (Cytochrome b) and
      ATPase6/8 gene sequences of mitochondrial DNA. Analysis of 133 sequences of Cyt b
      (1141 bp) and 130 sequences of ATPase6/8 gene (842 bp) revealed 47 and 44
      haplotypes, respectively. The estimated haplotype and nucleotide diversity was
      high in River Jia Bhoreli (Bhalukpong) population (h = 1.00000, pi = 0.007121 for
      Cyt b and h = 0.90441 pi = 0.004867 for ATPase6/8). Results of AMOVA indicated
      that majority of the genetic variations in both genes were due to variation among
      populations (60.79% for Cyt b and 51.41% for ATPase6/8 gene). The pairwise F(ST)
      comparison and neighbor-joining tree revealed high genetic divergence of River
      Jia Bhoreli population from other populations. The understanding of genetic
      variations of T. putitora populations will play a key role in conservation and
      management of this endangered fish species.

PMID- 24020998
TI  - The complete mitochondrial genome of Chinese glass lizard Ophisaurus harti
      (Squamata: Anguidae).
AB  - The complete mitochondrial genome of Ophisaurus harti is a circular molecule of
      17,163 bp in length, containing 13 protein-coding genes, 2 ribosomal RNAs, 22
      transfer RNAs and a control region. The A + T content of the overall base
      composition of H-strand is 54.9% (T: 23.4%; C: 30.8%; A: 31.5%; G: 14.3%). COI
      gene begins with GTG as start codon, while other 12 protein-coding genes start
      with a typical ATG initiation codon. ND1. COI. ATP8. ATP6. ND4L and ND5 genes are
      terminated with TAA as stop codon, ND2. ND6 and Cyt b end with TAG, COIII ends
      with TA, COII and ND3 end with T and ND4 ends with TG.

PMID- 24020999
TI  - Complete female mitochondrial genome of Anodonta anatina (Mollusca: Unionidae):
      confirmation of a novel protein-coding gene (F ORF).
AB  - Freshwater mussels are among animals having two different, gender-specific
      mitochondrial genomes. We sequenced complete female mitochondrial genomes from
      five individuals of Anodonta anatina, a bivalve species common in palearctic
      ecozone. The length of the genome was variable: 15,637-15,653 bp. This variation
      was almost entirely confined to the non-coding parts, which constituted
      approximately 5% of the genome. Nucleotide diversity was moderate, at 0.3%.
      Nucleotide composition was typically biased towards AT (66.0%). All genes
      normally seen in animal mtDNA were identified, as well as the ORF characteristic
      for unionid mitochondrial genomes, bringing the total number of genes present to
      38. If this additional ORF does encode a protein, it must evolve under a very
      relaxed selection since all substitutions within this gene were non-synonymous.
      The gene order and structure of the genome were identical to those of all female
      mitochondrial genomes described in unionid bivalves except the Gonideini.

PMID- 24021000
TI  - Complete mitochondrial genome of sterlet (Acipenser ruthenus).
AB  - The complete mitochondrial genome of sterlet (Acipenser ruthenus) was determined
      in this study. The mitogenome is 16,790 bp in length and contains 13 protein
      coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 2 non-coding
      regions (the control region and the putative origin of the light strand
      replication) with a typical vertebrate mitochondrial gene arrangement. The
      overall base composition of the heavy strand is 30.26% for A, 29.00% for C,
      16.23% for G and 24.51% for T, with a slight AT bias of 54.77%.

PMID- 24021002
TI  - The complete mitochondrial genome sequence of Metzia formosae (Cypriniformes,
      Cyprinidae).
AB  - We determined the complete mitochondrial genome (mitogenome) sequence of Metzia
      formosae, which is known as an endangered freshwater species in Taiwan and
      mainland China, with a long polymerase chain reaction (PCR) method. The total
      length of M. formosae mitogenome is 16,614 bp, consisting of 13 protein-coding
      genes, 22 transfer RNAs, 2 ribosomal RNAs genes and a noncoding control region.
      The overall base composition of M. formosae is 31.39% for A, 25.56% for T, 16.23%
      for G and 26.82% for C, with a slight AT bias of 56.95%. The molecular data here
      we presented could play a useful role not only for studying the evolutionary
      relationships and population genetics of Metzia species, but for practicing
      conservation on endangered fishes.

PMID- 24021001
TI  - Complete mitochondrial genome of the sixbar grouper Epinephelus sexfasciatus
      (Perciformes: Epinephelidae).
AB  - In this study, we presented the complete mitogenome for the sixbar grouper
      Epinephelus sexfasciatus. The complete mitogenome of E. sexfasciatus is 16,786 bp
      in length with the typical mitochondrial gene order and composition in
      vertebrates. Overall base composition was 28.40% A, 27.93% C, 27.21% T and 16.45%
      G. The COI gene used GTG and the ATP6 gene used CTG as the start codon. The tRNA
      Ser2 lost the dihydrouridine arm and replaced with a simple loop. Both the
      maximum likelihood (ML) and Bayesian inference (BI) methods yielded the same tree
      topology using available mitogenomes of the genus Epinephelus. Epinephelus
      sexfasciatus was nested to E. akaara. E. awoara and E. fasciatomaculosus, and
      then combined with E. stictus formed a clade. 

PMID- 24021003
TI  - The complete mitogenome of the oriental sucking barb, Garra orientalis
      (Cypriniformes, Cyprinidae): repetitive sequences in the control region.
AB  - The oriental sucking barb, Garra orientalis, is a small to moderate-sized
      freshwater fish. In this study, the complete mitochondrial genome of G. oriental
      was successfully sequenced for the first time with total length of 17,288 bp. The
      genome structure consists of 13 protein-coding genes, 2 ribosomal RNA genes, 22
      transfer RNA (tRNA) genes and a control region. Moreover, tandem repeat unit
      ranged from 259 to 260 bp (repeated 3-4 times) was identified in the control
      region among G. orientalis individuals.

PMID- 24021004
TI  - The first mitochondrial genome from Mysida (Crustacea: Malacostraca) reveals an
      unusual gene arrangement.
AB  - This is the first report to present the Neomysis orientalis mitochondrial genome
      as a representative from the order Mysida. While mitochondrial protein-coding
      genes (PCGs) commonly use several alternatives to ATN as start codons, all 13
      PCGs in N. orientalis mitochondrial genome initiate with ATG or ATA. Five PCGs
      (atp6. atp8. cob. nad4 and nad4L) start with ATG, while the other genes (cox1-3.
      nad1-3. nad5 and nad6) start with ATA. Only two PCGs (cox2 and nad2) in the N.
      orientalis mitochondrial genome end with incomplete stop codons (T- or TA-), and
      all the remaining ones have TAA or TAG stop codon. Only one PCG (nad4L) is
      encoded on the light strand and all other 12 PCGs are located at the heavy
      strand. Both rRNAs (srRNA and lrRNA) are encoded on the light strand. In common
      with 15 of the other 18 mitochondrial genomes from Peracarida, the major gene
      arrangement in the N. orientalis mitochondrial genome is different from the
      pancrustacean ground pattern. The largest conserved gene block in N. orientalis
      only contains two genes but those in the other 18 peracarid mitochondrial genomes
      contain more than five genes. Thus, the N. orientalis mitochondrial genome, as
      the first mitochondrial genome from the order Mysida, reveals an unusual gene
      arrangement that is unique compared with the other malacostracan mitochondrial
      genomes.

PMID- 24021006
TI  - Complete mitochondrial genome of Pseudorasbora elongata (Cypriniformes:
      Cyprinidae).
AB  - Phylogenetic placement of Pseudorasbora elongate remains unresolved. We
      determined the first complete mitochondrial genome of P. elongate that its
      mitogenome data should contribute to clarify the systematics of Pseudorasbora
      fishes. The mitogenome was 16,607 bp in length, including 13 typical protein
      coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes and 1 control region.
      The overall base composition of the heavy strain was 31.1% for A, 24.8% for C,
      28.2% for T and 15.9% for G, with the A + T bias of 59.3%.

PMID- 24021005
TI  - Mitochondrial phylogeny reveals cryptic genetic diversity in the genus Niviventer
      (Rodentia, Muroidea).
AB  - Niviventer is a muroid genus with 17 species widely distributed in East and
      Southeast Asia. These animals are important components of both extant and fossil
      small mammal communities, and they are among the most common infectious agents in
      humans. In this study, we employed partitioned Bayesian and relaxed clock
      divergence dating analyses and included the Niviventer mitochondrial cytochrome b
      genes of from GenBank (n = 223). Although the intra-generic relationships were
      not fully resolved, we recognized four major clades/subclades that could support
      further division of the genus. Paraphyletic and polyphyletic species were
      discovered, and 21 putative species were recognized through species delimitation
      analysis, which indicated an imperfect taxonomy and the existent of cryptic
      species. Molecular dating supported Niviventer origination in the late Miocene,
      and relatively higher diversification rates were observed in the late Pliocene
      and the Pleistocene, which might correlate with climate fluctuations.

PMID- 24021007
TI  - Complete mitochondrial genome of the grass moth Glyphodes quadrimaculalis
      (Lepidoptera: Crambidae).
AB  - Glyphodes quadrimaculalis (Lepidoptera: Crambidae) feed on a root tuber of
      Cynanchum wilfordii (Asclepiadaceae), which is one of the most famous traditional
      medicines in Korea. The genus Glyphodes includes ~ 130 species distributed
      worldwide, so the complete mitochondrial genome (mitogenome) would be helpful for
      bio-identification, biogeographic studies and multigene-based phylogeny. The
      15,255 bp long G. quadrimaculalis genome comprises 37 typical genes and 1 large
      non-coding region, with the typical arrangement found in Lepidoptera. Of the 13
      protein coding genes (PCGs), 12 begin with typical start codons found in insect
      mitochondrial PCGs, but the COI gene starts with atypical CGA. One of the
      noteworthy features of the genome includes the presence of a 51-bp long non
      coding space sequence located between tRNA(Gln) and ND2 that reveals high
      sequence homology (71.4%) to the neighboring ND2 gene, indicating the origin of
      the region by partial duplication of the ND2 gene.

PMID- 24021008
TI  - Sequence polymorphisms in the D-loop region of mitochondrial DNA and outcome of
      non-Hodgkin lymphoma.
AB  - Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop
      (D-loop) of mitochondrial DNA (mtDNA) might be associated with cancer risk and
      disease outcome. We have identified 140 SNPs including 26 SNPs with frequency
      distribution of minor allele greater than 5% in a case-control study for non
      Hodgkin lymphoma patients previously. In this study, we assessed the predictive
      power of D-loop SNPs in NHL patients. Five SNP sites were identified by log-rank
      test for statistically significant prediction of NHL survival in a univariate
      analysis. In an overall multivariate analysis, allele 16304 was identified as an
      independent predictor of NHL outcome. The survival time of NHL patients with
      16304C was significantly shorter than that of patients with 16304T (relative
      risk, 0.513; 95% CI, 0.266-0.989; p = 0.046). The analysis of genetic
      polymorphisms in the mitochondrial D-loop can help identify subgroups of patients
      who are at a high risk of a poor disease outcome. 

PMID- 24021009
TI  - The complete mitochondrial genome of Blue Pansy, Junonia orithya (Lepidoptera:
      Nymphalidae: Nymphalinae).
AB  - The complete mitochondrial genome (mitogenome) of Junonia orithya Linnaeus
      (Lepidoptera: Nymphalidae: Nymphalinae) is determined to be 15,214 bp in length,
      including 37 typical mitochondrial genes and an AT-rich region. Its gene order
      and orientation are identical to those of other butterfly species. All PCGs are
      initiated by typical ATN codons, except for cox1 gene which is started by CGA
      codon. Nine genes use complete termination codon (TAA), whereas the cox1. cox2.
      nad1 and nad4 genes end with single T. Except for trnS1(AGN), all tRNA genes
      display typical secondary cloverleaf structures as those of other insects. The
      331 bp long AT-rich region contains several features common to the other
      lepidopterans, such as the ATAGA motif followed by a 18 bp poly-T stretch, two
      microsatellite-like (TA)9 elements, a 5 bp poly-A stretch immediately upstream of
      trnM gene.

PMID- 24021010
TI  - Mitochondrial genome of Protobothrops cornutus (Squamata: Viperidae: Crotalinae).
AB  - Protobothrops cornutus is the endangered snake which is distributed narrowly in
      southern China and other adjacent countries of Asia. We determined the complete
      mitochondrial genome of P. cornutus (HB-pc20090810). The circle genome with the
      17,219 bp total length contained 13 protein-coding genes, 22 transfer RNA genes,
      2 ribosomal RNA genes and 2 control regions. Overall base composition of the
      complete mtDNA was 33.18% A, 24.80% T, 29.43% C and 12.58% G. All the genes in P.
      cornutus were distributed on the H-strand, except for the ND6 subunit gene and
      eight tRNA genes which were encoded on the L-strand.

PMID- 24021011
TI  - Complete mitochondrial genome of the Korean ikonnikov's bat Myotis ikonnikovi
      (Chiroptera: Vespertilionidae).
AB  - We have characterized the complete mitochondrial genome of a Korean ikonnikov's
      bat species, Myotis ikonnikovi. Total length of the mitogenome is 16,585 bp with
      a total base composition of 34.0% A, 30.4% T, 22.8% C and 12.8% G. The mitogenome
      consists of 13 protein-coding genes, 2 rRNA (12S and 16S RNA) genes, 22 tRNA
      genes and 1 control region. The mitogenome of M. ikonnikovi exhibited similar
      features compared with the previously determined mitogenome of a Myotis species,
      M. formosus. The results will contribute to our understanding of the mechanisms
      underlying mitogenome evolution in the genus Myotis bats.

PMID- 24021012
TI  - Single nucleotide polymorphisms in the D-loop region of mitochondrial DNA is
      associated with renal cell carcinoma outcome.
AB  - Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop
      (D-loop) of mitochondrial DNA (mtDNA) has been described in various types of
      cancers and might be associated with cancer risk and disease outcome. We
      identified 14 SNPs with a frequency higher than 5% and 5 SNPs associated with the
      risk of renal cell carcinoma (RCC) in a case-control study previously. In the
      present study, we assessed the relationship of these SNPs and the outcome of RCC
      patients, a SNP of 262C/T was identified by the log-rank test for statistically
      significant prediction of RCC survival. In an overall multivariate analysis,
      allele 262 was identified as an independent predictor of RCC outcome. The length
      of survival of patients with 262T was significantly shorter than that of patients
      with allele 262C (relative risk, 2.136, 95%CI, 1.863-2.449; p = 0.000). The
      analysis of genetic polymorphisms in the mitochondrial D-loop can help identify
      patients subgroup at high risk of a poor disease outcome.

PMID- 24021013
TI  - The complete mitochondrial genome of Anas poecilorhyncha (Anatidae: Anas).
AB  - The mitochondrial genome of Anas poecilorhyncha (Anatidae: Anas) is a circular
      molecule of 16,608 bp in length, containing 13 protein-coding genes, 2 ribosomal
      RNA genes, 22 transfer RNA genes and 1 control region (D-loop). Overall base
      composition of the complete mitochondrial DNA was 29.17% A, 22.21% T, 32.81% C
      and 15.81% G.

PMID- 24021014
TI  - The role of mitochondrial tRNAPhe C628T variant in deafness expression.
AB  - Mutations in mitochondrial genome are one of the most important causes of hearing
      loss, of these, mitochondrial tRNA (mt-tRNA) genes are the hot spots for
      mutations associated with deafness. Most recently, a novel mt-tRNA(Phe) C628T
      variant has been reported to be associated with non-syndromic and sensorineural
      hearing loss. To test this association, we characterized the C628T variant using
      a phylogenetic approach; in addition, we employed the bioinformatics tool to
      predict the thermodynamic change of the mt-tRNA(Phe) gene with and without this
      variant. Intriguingly, the C628T variant was not evolutionary conserved and had
      little effect on mt-tRNA(Phe) folding. Moreover, through the application of the
      pathogenicity scoring system, we classified the C628T variant as a "neutral
      polymorphism", suggesting that this variant currently lacked sufficient evident
      to support as a "pathogenic" mutation. 

PMID- 24021015
TI  - The complete F-type mitochondrial genome of threatened Chinese freshwater mussel
      Solenaia oleivora (Bivalvia: Unionidae: Gonideinae).
AB  - The freshwater mussel Solenaia oleivora is considered threatened due to
      anthropogenic habitat modification and pollution. The complete F-type
      mitochondrial genome (mitogenome) of S. oleivora was first determined (GenBank
      accession no. KF296320). The length of this mitogenome is 16,392 bp with an AT
      content of 59.9%. There are 37 typical animal mitochondrial genes and a putative
      control region. Within the control region, 5 tandem repeats of a 106 bp element
      were identified. The gene order rearrangement of cox2-rrnS in F-type mitogenome
      compared to that of other freshwater mussels, is not unique for S. oleivora, but
      is shared with all other available freshwater mussels in the subfamily
      Gonideinae. The complete mitogenome can provide a basic data for the further
      studies on molecular taxonomy, phylogenetic analyses and conservation genetics.

PMID- 24021016
TI  - Effects of vermilion height on lip esthetics in Japanese and Korean orthodontists
      and orthodontic patients.
AB  - OBJECTIVE: To evaluate the influence of vermilion height on the assessment of lip
      attractiveness by Japanese and Korean orthodontists and orthodontic patients.
      MATERIALS AND METHODS: Vermilion heights were modified by increasing or
      decreasing the vermilion height in 1.0-mm increments from -3.0 mm to 3.0 mm with
      reference to an average vermilion height. Participants ranged from 15 to 29 years
      of age and comprised 29 Japanese and 25 Korean orthodontists and 96 Japanese and
      72 Korean orthodontic patients. They all rated the attractiveness of seven images
      with altered vermilion height using a visual analog scale. RESULTS: Across the
      participant groups, there were significant differences in the median esthetic
      scores for the seven vermilion height levels tested. The Japanese and Korean
      raters assigned the highest scores to the average vermilion height and assigned
      the lowest scores to the +3-mm increased vermilion height. The ranges of
      vermilion height preferred by orthodontists were found to be within the ranges
      preferred by orthodontic patients when evaluating the preferences in lip
      esthetics by country. CONCLUSIONS: We conclude that the -1-mm to +1-mm range for
      the average vermilion height is considered attractive for lips for both Japanese
      and Korean people.

PMID- 24021017
TI  - Topical henna ameliorated capecitabine-induced hand-foot syndrome.
AB  - BACKGROUND: Hand-foot syndrome (HFS) is the most frequently reported side effect
      of oral capecitabine therapy. In addition to treatment interruption and dose
      reduction, supportive treatments can help alleviate symptoms. Although its
      efficacy has not been proven in clinical studies, certain authors report on the
      use of prophylactic or therapeutic pyridoxine supplementation for the prevention
      of minimization to be useful in preventing worsening of HFS but are no substitute
      for dose modifications. CASE REPORT: We report a case of an interesting
      observation in a patient with pancreatic cancer receiving capecitabine whose HFS
      was improved with the use of "henna". DISCUSSION: Henna has been used for
      histories as a medicine, preservative, and cosmetic. Our case underlines the
      basis to further evaluate the anti-inflammatory, antipyretic, and analgesic
      effects of henna. We encourage other investigators to publish any similar cases
      or any other herbal or non-drug therapies. HFS is a common side effect of many
      drugs, including capecitabine, sorafinib and regorafenib. HFS is bothersome for
      patients even in low grades and impacts quality of life of patients. HFS cannot
      be prevented and currently the treatments aimed at controlling syndrome are not
      very effective. Exploring other potential treatment or management options such as
      henna is of high value.

PMID- 24021019
TI  - Formal redox potentials of organic molecules in ionic liquids on the basis of
      quaternary nitrogen cations as adiabatic electron affinities.
AB  - Formal redox potentials E degrees ' involving neutral species R and radical
      anions R(*-) in ionic liquids (ILs) composed of ammonium, pyridinium, and
      imidazolium cations are discussed from the point of view of the adiabatic
      electron affinity as a molecular property. The dependence of the 1,4-benzoquinone
      (BQ)/BQ(*-) redox process in CH2Cl2 and CH3CN is primarily investigated over a
      wide concentration range of ILs as the supporting electrolyte. A logarithmic
      relationship involving a positive shift of E degrees ' with increasing
      concentration is obtained when the concentration is changed from 0.01 to 1.0 M.
      The relationship of E degrees ' at IL concentrations greater than 1.0 M gradually
      reaches a plateau and remains there even for the neat ILs. It is found that the E
      degrees ' values in the neat ILs are not influenced by the measurement
      conditions, and that they remain considerably dependent on the nature and
      concentration of the electrolyte when measured using the traditional method
      involving molecular solvents combined with a supporting electrolyte (0.1-0.5 M).
      The difference in the E degrees ' values observed in the ammonium and pyridinium
      ILs is only several millivolts. In addition, ESR and self-consistent isodensity
      polarized continuum model calculation results reveal that the potential shift
      toward positive values upon the transition from molecular solvents containing ILs
      to neat ILs is adequately accounted for by changes in the electrostatic
      interaction of R(*-) taken into the cavity composed of the solvent and IL. On the
      other hand, the first reduction waves of quinones, electron-accepting molecules,
      and polynuclear aromatic hydrocarbons are reversibly or quasi-reversibly observed
      in the ILs. The electrochemical stability of the ILs is exploited in the facile
      measurement of these quasi-reversible waves at quite negative potentials, such as
      for the naphthalene (NP)/NP(*-) couple. Notably, the E degrees ' values obtained
      in the ammonium ILs correlate well with the calculated standard redox potentials
      and are linearly fitted with high correlation over all classes of compounds using
      a single regression equation based on Koopmans' theorem. 

PMID- 24021018
TI  - Evaluation of retinal nerve fiber layer thickness in vernal keratoconjunctivitis
      patients under long-term topical corticosteroid therapy.
AB  - PURPOSE: The aim of this study was to evaluate the retinal nerve fiber layer
      (RNFL) thickness in vernal keratoconjunctivitis (VKC) patients who were under
      long-term topical corticosteroid therapy. METHODS: Thirty-six eyes of 36 VKC
      patients with clear cornea and normal videokeratography and 40 eyes of 40 age-
      and gender-matched normal children were included in the study. Clinical and
      demographic characteristics of the patients were noted and detailed
      ophthalmological examination was performed. Visual acuity (VA), spherical
      equivalent (SE), axial length (AL) and RNFL thickness measurements were compared
      between the groups. To correct ocular magnification effect on RNFL, we used
      Littmann's formula. RESULTS: All VKC patients had history of topical
      corticosteroid use and the mean duration of the topical corticosteroid use was
      23.8 +/- 9.09 months. There was no significant difference between the groups in
      terms of intraocular pressure (IOP). VKC group had significantly worse VA,
      greater SE and AL and thinner mean global, superior and inferior RNFL thickness.
      There were significant negative correlations between the duration of topical
      corticosteroid use and the mean global, superior and temporal RNFL thickness in
      VKC group. After correction of magnification effect, VKC group still had thinner
      mean global, superior and inferior RNFL thickness, and significant difference
      between the groups in inferior RNFL thickness did not disappear. CONCLUSION:
      Significant RNFL thickness difference between the groups suggests a possible
      effect of long-term corticosteroid use in VKC patients. Because visual field (VF)
      analysis in pediatric patients is difficult to perform and IOP may be illusive,
      RNFL thickness measurements in addition to routine examinations in VKC patients
      may help clinicians in their practice.

PMID- 24021020
TI  - Prosthetic restoration in the single-tooth gap: patient preferences and analysis
      of the WTP index.
AB  - OBJECTIVE: The objective of this study was to evaluate the preference of a
      patients' population, according to the index of willingness to pay (WTP), against
      two treatments to restore a single-tooth gap: the implant-supported crown (ISC)
      and the 3-unit fixed partial denture prosthesis (FPDP) on natural teeth.
      MATERIALS AND METHODS: Willingness to pay values were recorded on 107 subjects by
      asking the WTP from a starting bid of ?2000 modifiable through monetary increases
      or decreases (?100). Data were collected through an individually delivered
      questionnaire. The characteristics of the population and choices made, the median
      values and WTP associations with socio-demographic parameters (Mann-Whitney and
      Kruskal-Wallis tests), correlations between variables (chi-square test in
      contingency tables) and significant parameters for predicting WTP values obtained
      in a multiple linear regression model were revealed. RESULTS: The 64% of patients
      expressed a preference for ISC, while the remaining 36% of the population chose
      the FPDP. The current therapeutic choice and those carried out in the past were
      generally in agreement (>70% of cases, P = 0.0001); a relationship was discovered
      between the anterior and posterior area to the same method of rehabilitation (101
      of 107 cases, 94.4%). The WTP median values for ISC were of ?3000 and of ?2500 in
      the anterior and posterior areas, respectively. The smallest amount of money has
      been allocated for FPDP in posterior region (median of ?1500). The "importance of
      oral care" for the patient was a significant predictor, in the regression model
      analysis, for the estimation of both anterior (P = 0.0003) and posterior (P <
      0.0001) WTP values. The "previous therapy" variable reached and was just close to
      significance in anterior (P = 0.0367) and posterior (P = 0.0511) analyses,
      respectively. CONCLUSIONS: Within the limitations of this study, most of the
      population (64%) surveyed indicated the ISC as a therapeutic solution for the
      replacement of a single missing tooth, showing a higher WTP index in the anterior
      area. Among investigated socio-demographic variables, the importance assigned by
      the patient to oral care appeared to influence WTP values of the rehabilitation,
      regardless the location of the single gap in the mouth.

PMID- 24021023
TI  - Dynamics of an intrinsically disordered protein reveal metastable conformations
      that potentially seed aggregation.
AB  - Amyloid fibril deposits of the intrinsically disordered hIAPP peptide are found
      in 95% of type II diabetes patients, and the aggregation of this peptide is
      suggested to induce apoptotic cell-death in insulin-producing beta-cells.
      Understanding the structure and dynamics of the hIAPP monomer in solution is thus
      important for understanding the nucleation of aggregation and the formation of
      oligomers. In this study, we identify the metastable conformational states of the
      hIAPP monomer and the dynamics of transitioning between them using Markov state
      models constructed from extensive molecular dynamics simulations. We show that
      the overall structure of the hIAPP peptide is random coil-like and lacks a
      dominant folded structure. Despite this fact, our model reveals a large number of
      reasonably well-populated metastable conformational states (or local free energy
      minima) having populations of a few percent or less. The time scales for
      transitioning between these states range from several microseconds to
      milliseconds. In contrast to folded proteins, there is no kinetic hub. More
      strikingly, a few states contain significant amounts of beta-hairpin secondary
      structure and extended hydrophobic surfaces that are exposed to the solvent. We
      propose that these states may facilitate the nucleation of hIAPP aggregation
      through a significant component of the conformational selection mechanism,
      because they may increase their populations upon aggregation by promoting
      hydrophobic interactions and at the same time provide a flat geometry to seed the
      ordered beta-strand packing of the fibrils. 

PMID- 24021024
TI  - High-efficiency nanostructured window GaAs solar cells.
AB  - Nanostructures have been widely used in solar cells due to their extraordinary
      optical properties. In most nanostructured cells, high short circuit current has
      been obtained due to enhanced light absorption. However, most of them suffer from
      lowered open circuit voltage and fill factor. One of the main challenges is
      formation of good junction and electrical contact. In particular, nanostructures
      in GaAs only have shown unsatisfactory performances (below 5% in energy
      conversion efficiency) which cannot match their ideal material properties and the
      record photovoltaic performances in industry. Here we demonstrate a completely
      new design for nanostructured solar cells that combines nanostructured window
      layer, metal mesa bar contact with small area, high quality planar junction. In
      this way, we not only keep the advanced optical properties of nanostructures such
      as broadband and wide angle antireflection, but also minimize its negative impact
      on electrical properties. High light absorption, efficient carrier collection,
      leakage elimination, and good lateral conductance can be simultaneously obtained.
      A nanostructured window cell using GaAs junction and AlGaAs nanocone window
      demonstrates 17% energy conversion efficiency and 0.982 V high open circuit
      voltage. 

PMID- 24021022
TI  - Functional redundancy between trans-Golgi network SNARE family members in
      Arabidopsis thaliana.
AB  - BACKGROUND: Vesicle fusion is an essential process for maintaining the structure
      and function of the endomembrane system. Fusion is mediated by t-SNARE (soluble N
      ethylmaleimide-sensitive factor attachment protein receptor) fusion proteins on
      the target membrane and v-SNAREs on the vesicle membrane; v-and t-SNAREs interact
      with each other, driving vesicle fusion with the target membrane. The Arabidopsis
      thaliana trans-Golgi network resident SNAREs SYP41 and VTI12, along with
      YKT61/62, have been shown to function in vesicle fusion in vitro, consistent with
      immunoprecipitation results showing their interaction in Arabidopsis cell
      extracts. Conflicting published results have indicated that SYP4 family members
      are either functionally redundant or have distinct and essential functions; the
      reason for this discrepancy is unclear. RESULTS: Here we used a proteoliposome
      fusion assay to demonstrate that SYP42 and SYP43 can substitute for SYP41 in
      driving lipid mixing, providing support for functional overlap between family
      members. Previous reports have also suggested that VTI11 and VTI12 SNAREs show
      partial overlap in function, despite having mostly distinct localizations and
      binding partners. We show that VTI11 can substitute for VTI12 in in vitro lipid
      mixing reactions, providing molecular support for the genetic evidence for
      partial functional redundancy in vivo. CONCLUSIONS: Our data provide biochemical
      evidence for functional overlap in membrane fusion between members of the SYP4 or
      VTI1 SNARE groups, supporting previous genetic data suggesting redundancy.

PMID- 24021025
TI  - Preclinical toxicology and biodistribution studies of recombinant adeno
      associated virus 1 human acid alpha-glucosidase.
AB  - A biodistribution and toxicology study was performed to test the acute toxicities
      of intradiaphragmatic injection of a recombinant adeno-associated virus (rAAV)
      2/1-human acid alpha-Glucosidase (hGAA) driven by a cytomegalovirus (CMV)
      promoter (rAAV1-CMV-hGAA) in New Zealand white rabbits and in the rodent Pompe
      disease model by injecting at the right quadriceps. Studies performed using
      fluoroscopy and AAV2-GFP demonstrated spread upon intradiaphragmatic injection,
      and the ability of AAV to infect and express acid alpha-glucosidase (GAA)
      throughout the diaphragm. For the preclinical study, 10 rabbits (5 male, 5
      female) were divided into two groups, vehicle control (Lactated Ringer's) and
      test article (1.5*10(12) vector genomes [vg] rAAV1-CMV-hGAA), and euthanized on
      day 21. After direct visualization, the left hemidiaphragm was injected at three
      locations. There was up to a 2,500-fold increase in circulating anti-AAV1
      antibodies directed to the vector capsids. In addition, up to an 18-fold increase
      in antibodies against the GAA protein was generated. Injection sites maintained
      up to 1.0*10(5) vg/MUg genomic DNA (gDNA), while uninjected sites had up to
      1.0*10(4) vg/MUg gDNA. Vector DNA was present in blood at 24 hr postinjection at
      up to 1.0*10(6) vg/MUg gDNA, followed by a decrease to 1.0*10(3) vg/MUg gDNA at
      euthanization on day 21. Nominal amounts of vector DNA were present in peripheral
      organs, including the brain, spinal cord, gonads, and skeletal muscle. Upon
      histopathological examination, fibroplasias of the serosal surface were noted at
      diaphragm injections sites of both groups. In addition, an increase in
      mononuclear cell infiltration in the diaphragm and esophagus in vector-dosed
      animals was found. Elevated creatine phosphokinase levels, an indicator of muscle
      repair, was observed in all animals postprocedure but persisted in vector
      injected rabbits until euthanization. A follow-up study suggested that this was
      directed against the human transgene expression in a foreign species. Overall,
      this study demonstrates diffusion of vector throughout the diaphragm after
      localized injections.

PMID- 24021021
TI  - Association of breakfast consumption with objectively measured and self-reported
      physical activity, sedentary time and physical fitness in European adolescents:
      the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study.
AB  - OBJECTIVE: To examine the association of breakfast consumption with objectively
      measured and self-reported physical activity, sedentary time and physical
      fitness. DESIGN: The HELENA (Healthy Lifestyle in Europe by Nutrition in
      Adolescence) Cross-Sectional Study. Breakfast consumption was assessed by two non
      consecutive 24 h recalls and by a 'Food Choices and Preferences' questionnaire.
      Physical activity, sedentary time and physical fitness components
      (cardiorespiratory fitness, muscular fitness and speed/agility) were measured and
      self-reported. Socio-economic status was assessed by questionnaire. SETTING: Ten
      European cities. SUBJECTS: Adolescents (n 2148; aged 12.5-17.5 years). RESULTS:
      Breakfast consumption was not associated with measured or self-reported physical
      activity. However, 24 h recall breakfast consumption was related to measured
      sedentary time in males and females; although results were not confirmed when
      using other methods to assess breakfast patterns or sedentary time. Breakfast
      consumption was not related to muscular fitness and speed/agility in males and
      females. However, male breakfast consumers had higher cardiorespiratory fitness
      compared with occasional breakfast consumers and breakfast skippers, while no
      differences were observed in females. Overall, results were consistent using
      different methods to assess breakfast consumption or cardiorespiratory fitness
      (all P <= 0.005). In addition, both male and female breakfast skippers (assessed
      by 24 h recall) were less likely to have high measured cardiorespiratory fitness
      compared with breakfast consumers (OR = 0.33; 95% CI 0.18, 0.59 and OR = 0.56;
      95%CI 0.32, 0.98, respectively). Results persisted across methods. CONCLUSIONS:
      Skipping breakfast does not seem to be related to physical activity, sedentary
      time or muscular fitness and speed/agility as physical fitness components in
      European adolescents; yet it is associated with both measured and self-reported
      cardiorespiratory fitness, which extends previous findings.

PMID- 24021026
TI  - Hyperemesis gravidarum and birth outcomes-a population-based cohort study of 2.2
      million births in the Norwegian Birth Registry.
AB  - OBJECTIVE: To study associations between hyperemesis gravidarum (HG) and birth
      outcomes. DESIGN: Population-based cohort study. SETTING: Norway. SAMPLE:
      Singleton births in the Norwegian Birth Registry, 1967-2009 (n = 2 270 363).
      METHODS: Multiple logistic regression was applied to study associations between
      HG and dichotomous outcomes; multiple linear regression to study associations
      between HG, birthweight and gestational length. Generalised estimating equations
      were applied to obtain valid standard errors. Sub-analysis on data with available
      information on smoking was conducted (1999-2009). MAIN OUTCOME MEASURES: Small
      and large for gestational age (SGA/LGA), Apgar score after 5 minutes, very
      preterm and preterm birth (VPTB/PTB), perinatal death, stillbirth, neonatal
      death, birthweight and gestational length. RESULTS: No associations between HG
      and adverse pregnancy outcomes were observed in crude analyses, except for VPTB
      (odds ratio [OR] 0.79, 95% CI 0.67-0.93). In adjusted analysis, HG was associated
      with perinatal death (OR 1.27, 95% CI 1.08-1.48). Inverse associations were
      observed between HG and VPTB (OR 0.80, 95% CI 0.68-0.94) and LGA (OR 0.95, 95% CI
      0.90-0.99). Sub-analyses showed no associations between HG and perinatal death
      (OR 1.29, 95% CI 0.91-1.83). The inverse associations between HG, VPTB and LGA
      were strengthened (OR 0.66, 95% CI, 0.48-0.91 and OR 0.86, 95% CI 0.79-0.93,
      respectively). Exposed babies had reduced birthweight and gestational length
      compared with unexposed, adjusted difference - 21.4 g and - 0.5 days,
      respectively. Adjustment for smoking slightly strengthened the impact of HG on
      birthweight. CONCLUSIONS: Inverse associations for HG and VPTB and LGA were
      observed. HG was associated with slight reductions in birthweight and gestational
      age.

PMID- 24021027
TI  - Effect of enhanced external counterpulsation treatment on renal function in
      cardiac patients.
AB  - BACKGROUND: Enhanced external counterpulsation (EECP) enhances coronary perfusion
      and reduces left ventricular afterload. However, the role of EECP on renal
      function in cardiac patients is unknown. Our aim was to assess renal function
      determined by serum cystatin C in cardiac patients before and after EECP
      treatment. METHODS: A prospective observational longitudinal study was conducted
      in order to evaluate renal function using serum cystatin C (Cys C) and estimated
      glomerular filtration rate (GFR) after 35 sessions of EECP treatment in 30
      patients with chronic stable angina and/or heart failure. The median (IQR) time
      for follow-up period after starting EECP treatment was 16 (10-24) months.
      RESULTS: Cys C significantly declined from 1.00 (0.78-1.31) to 0.94 (0.77-1.27)
      mg/L (p < 0.001) and estimated GFR increased from 70.47 (43.88-89.41) to 76.27
      (49.02-91.46) mL/min/1.73 m(2) (p = 0.006) after EECP treatment. Subgroup
      analysis showed that patients with baseline GFR <60 mL/min/1.73 m(2) or NT-proBNP
      >125 pg/mL had a significant decrease in Cys C when compared to other groups (p <
      0.01). CONCLUSIONS: The study demonstrated that EECP could improve long-term
      renal function in cardiac patients especially in cases with declined renal
      function or with high NT-proBNP. TRIAL REGISTRATION: The study was registered in
      the clinical trial as International Standard Randomized Controlled Trial Number
      ISRCTN11560035.

PMID- 24021028
TI  - Vasculitis-like hemorrhagic retinal angiopathy in Wegener's granulomatosis.
AB  - BACKGROUND: Granulomatosis with polyangiitis, also known as Wegener's
      granulomatosis, is a chronic systemic inflammatory disease that can also involve
      the eyes. We report a case of massive retinal and preretinal hemorrhages with
      perivascular changes as the initial signs in granulomatosis with polyangiitis
      (Wegener's granulomatosis). CASE PRESENTATION: A 39-year-old Caucasian male
      presented with blurred vision in his right eye, myalgia and arthralgia, recurrent
      nose bleeds and anosmia. Fundus image of his right eye showed massive retinal
      hemorrhages and vasculitis-like angiopathy, although no fluorescein extravasation
      was present in fluorescein angiography. Laboratory investigations revealed an
      inflammation with increased C-reactive protein, elevated erythrocyte
      sedimentation rate and neutrophil count. Tests for antineutrophil cytoplasmic
      antibodies (ANCA) were positive for c-ANCA (cytoplasmatic ANCA) and PR3-ANCA
      (proteinase 3-ANCA). Renal biopsy demonstrated a focal segmental necrotizing
      glomerulonephritis. Granulomatosis with polyangiitis (Wegener's granulomatosis)
      was diagnosed and a combined systemic therapy of cyclophosphamide and
      corticosteroids was initiated. During 3 months of follow-up, complete resorption
      of retinal hemorrhages was seen and general complaints as well as visual acuity
      improved during therapy. CONCLUSION: Vasculitis-like retinal changes can occur in
      Wegener's granulomatosis. Despite massive retinal and preretinal hemorrhages that
      cause visual impairment, immunosuppressive therapy can improve ocular symptoms.

PMID- 24021029
TI  - SumaRT/Nap vs naproxen sodium in treatment and disease modification of migraine:
      a pilot study.
AB  - OBJECTIVE: This pilot study explored the potential for 2 recognized acute
      migraine medications, 85 mg of sumatriptan plus 500 mg of naproxen sodium in a
      combination tablet (SumaRT/Nap) and 500 mg of naproxen sodium, to treat and
      modify the disease progression of migraine. In other words, can these medications
      both abort an acute attack of migraine and reduce the number of future migraine
      attacks? BACKGROUND: Patients suffering with moderate to severe attacks of
      migraine desire acute treatment. As migraine frequency increases, so does the
      need for more frequent relief of acute attacks. This may lead to medication
      overuse and potentially medication overuse headache (MOH). Ideally, acute
      medication would have the ability to abort an attack of migraine and reduce the
      likelihood of future attacks. STUDY DESIGN: The primary endpoint of this study
      was a reduction in migraine headache days from baseline through month 3 of the
      study. Subjects were randomized 1:1 to treat 14 or fewer migraines per month with
      SumaRT/Nap (Group A) or naproxen sodium (Group B) for 3 months. Subjects in group
      A utilized SumaRT/Nap were encouraged, but not required, to treat migraine
      headache within 1 hour of onset of headache when the pain was mild. They could re
      treat if needed after 2 hours. Subjects in group B utilized the same treatment
      strategy with 500 mg of naproxen sodium. Tablets of study medication were
      identical for both groups. Subjects recorded headache days, migraine attacks,
      duration of attacks, treatment, and treatment results daily on paper diaries.
      Subjects took the Migraine Disability Assessment Test (MIDAS) at randomization
      and 3 months later at the end of study. RESULTS: Naproxen sodium was associated
      with a statistically significant reduction in migraine headache days at month 3
      compared to baseline (P = .0002). SumaRT/Nap was also associated with a reduction
      of migraine headache days, but this decrease did not reach statistical
      significance (P = .2). In addition, subjects in the naproxen sodium group had a
      statistically significant reduction of migraine attacks in all 3 months of the
      study compared to baseline. A greater than 50% reduction in the number of
      migraine headache days at month 3 occurred in 43% (6/14) of subjects in group B
      compared to 17% (3/18) of subjects in group A. Consistent with large regulatory
      studies comparing the efficacy of SumaRT/Nap with naproxen sodium, SumaRT/Nap in
      this study was statistically superior to naproxen sodium at 2 hours in reducing
      headache severity during months 2 and 3. There was a reduction of acute
      medication used from baseline to month 3 and improvement in MIDAS scores for both
      groups. CONCLUSION: Naproxen sodium, when used as a sole acute treatment early in
      attacks, appears to reduce the frequency of headache days and migraine attacks
      for a select number of subjects over a 3-month period. SumaRT/Nap is more
      effective at 2-hour headache reduction than naproxen sodium alone, but has less
      impact on reducing attack frequency or the number of headache days. Both
      treatments were well tolerated, and there was no convincing evidence that either
      medication led to MOH.

PMID- 24021030
TI  - Acute renal failure and pregnancy: a seventeen-year experience of a Tunisian
      intensive care unit.
AB  - PURPOSE: To describe the epidemiologic features of acute renal failure related to
      pregnancy (PRARF) and to evaluate its prognostic impact. METHODS: Retrospective
      study conducted in a Tunisian intensive care unit over a period of 17 years (1995
      2011). Women were included if they were more than 20 weeks pregnant and were
      admitted to the ICU during pregnancy or immediately (<7 d) post partum. PRARF was
      defined by a serum creatinine level >0.8 mg/dL and was classified as mild (0.9 to
      1.4 mg/dL), moderate (1.5 to 2.9 mg/dL) or severe (>3 mg/dL). RESULTS: Five
      hundred and fifty patients were included. Mean age was 31 +/- 6 years. Mean SOFA
      score was 4 +/- 3. PRARF was diagnosed in 313 patients (56.9%). ARF was mild in
      215 cases (39.1%), moderate in 65 cases (11.8%) and severe in 33 cases (6%). Main
      causes leading to this complication were preeclampsia (66.5%) and acute
      hemorrhage (27.8%). Only two patients (0.4%) developed chronic renal failure and
      needed long-term dialysis. Patients who developed this complication had higher
      SOFA score (4.7 +/- 3.5 vs. 3.2 +/- 2.1; p < 0.001). Thirty-three patients (6%)
      died in the ICU. The rate of ICU mortality was significantly higher in patients
      with PRARF (9.3 vs. 1.7%; p < 0.001). CONCLUSIONS: PRARF is associated with
      higher mortality. Thus, appropriate monitoring of pregnancies is needed in order
      to prevent its onset by an early and prompt management of the underlying risk
      factors.

PMID- 24021031
TI  - Gitelman's syndrome associated with chondrocalcinosis: a case report.
AB  - Gitelman's syndrome (GS) is a rare disease with autosomal recessive trait,
      characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria
      and hyperkinemic hyperaldosteronism. While muscle weakness, tetany, stomachache,
      nausea and fever are very common, it could sometimes be completely asymptomatic
      as is the case in our patient. It is generally benign, but some severe
      complications like growth retardation and, though rare, paralysis and cardiac
      arrest could also be seen. A 57-year-old male patient sent to our hospital for
      further examination because of hypokalemia was diagnosed with GS as a result of
      clinical and laboratory assessments. Potassium and magnesium replacement was
      started. We are presenting our case seeing that GS is not a syndrome to be
      overlooked as it bears a risk of severe complications, although it might be
      asymptomatic until advanced ages.

PMID- 24021032
TI  - Vascular disease in early stage of diabetic nephropathy.

PMID- 24021036
TI  - Thiamine triphosphatase and the CYTH superfamily of proteins.
AB  - The CYTH superfamily of proteins was named after its two founding members, the
      CyaB adenylyl cyclase from Aeromonas hydrophila, and the human 25-kDa thiamine
      triphosphatase (ThTPase). Members of this superfamily of proteins exist in all
      organisms, including bacteria, archaeons, fungi, plants, and animals (except
      birds), and can be traced back to the last universal common ancestor. Their
      sequences include several charged residues involved in divalent cation and
      triphosphate binding. Indeed, all members of the CYTH superfamily that have been
      characterized act on triphosphorylated substrates and require at least one
      divalent metal cation for catalysis. In most cases, the enzyme-substrate complex
      adopts a tunnel-like (beta-barrel) conformation. The Nitrosomonas europaea,
      Escherichia coli and Arabidopsis thaliana CYTH proteins are specific inorganic
      tripolyphosphatases. We propose that inorganic tripolyphosphate, the simplest
      triphosphate compound, is the primitive substrate of CYTH proteins, other enzyme
      activities, such as adenylate cyclase (in A. hydrophila and Yersinia pestis),
      mRNA triphosphatase (in fungi and protozoans), and ThTPase (in metazoans), being
      secondary acquisitions. ThTPase activity is not limited to mammals, as sea
      anemone and zebrafish CYTH proteins are specific ThTPases. The acquisition of
      this enzyme activity is linked to the presence of a tryptophan involved in the
      binding of the thiazolium heterocycle of the thiamine molecule. Furthermore, we
      propose a conserved catalytic mechanism between a bacterial inorganic
      tripolyphosphatase and metazoan ThTPases, based on a catalytic dyad comprising a
      lysine and a tyrosine, explaining the alkaline pH optimum of these enzymes. 

PMID- 24021033
TI  - Goal-setting intervention in patients with active asthma: protocol for a pilot
      cluster-randomised controlled trial.
AB  - BACKGROUND: Supporting self-management behaviours is recommended guidance for
      people with asthma. Preliminary work suggests that a brief, intensive, patient
      centred intervention may be successful in supporting people with asthma to
      participate in life roles and activities they value. We seek to assess the
      feasibility of undertaking a cluster-randomised controlled trial (cRCT) of a
      brief, goal-setting intervention delivered in the context of an asthma review
      consultation. METHODS/DESIGN: A two armed, single-blinded, multi-centre, cluster
      randomised controlled feasibility trial will be conducted in UK primary care.
      Randomisation will take place at the practice level. We aim to recruit a total of
      80 primary care patients with active asthma from at least eight practices across
      two health boards in Scotland (10 patients per practice resulting in ~40 in each
      arm). Patients in the intervention arm will be asked to complete a novel goal
      setting tool immediately prior to an asthma review consultation. This will be
      used to underpin a focussed discussion about their goals during the asthma
      review. A tailored management plan will then be negotiated to facilitate
      achieving their prioritised goals. Patients in the control arm will receive a
      usual care guideline-based review of asthma. Data on quality of life, asthma
      control and patient confidence will be collected from both arms at baseline and 3
      and 6 months post-intervention. Data on health services resource use will be
      collected from all patient records 6 months pre- and post-intervention. Semi
      structured interviews will be carried out with healthcare staff and a purposive
      sample of patients to elicit their views and experiences of the trial. The
      outcomes of interest in this feasibility trial are the ability to recruit
      patients and healthcare staff, the optimal method of delivering the intervention
      within routine clinical practice, and acceptability and perceived utility of the
      intervention among patients and staff. TRIAL REGISTRATION: ISRCTN18912042.

PMID- 24021037
TI  - [Effectiveness of norepinephrine versus dopamine for septic shock: a meta
      analysis].
AB  - OBJECTIVE: To systematically evaluate the effect of norepinephrine and dopamine
      on patients with septic shock. METHODS: Randomized controlled trials (RCTs) about
      treatment of adults with septic shock with norepinephrine and dopamine were
      selected from PubMed, Embase, the Cochrane Library, CBM and CNKI databases. Meta
      analysis concerning the effect of norepinephrine and dopamine on hemodynamics and
      metabolism of patients with septic shock was conducted by using Review Manager
      5.0 software. The results were expressed as risk ratio (RR) for dichotomous
      outcomes or standardized mean difference (SMD) for continuous data with 95%
      confidence intervals (95%CI). RESULTS: Eleven trials with 1718 cases were
      enrolled. Meta analysis showed that compared with dopamine, norepinephrine could
      decrease the mortality (RR=0.89, 95%CI 0.81-0.98, P=0.02). There were a decreased
      heart rate (SMD=-2.23, 95%CI -3.76 to -0.71, P=0.004), cardiac index (SMD=-0.71,
      95%CI -1.07 to -0.35, P=0.0001) and an increased systemic vascular resistance
      index (SMD=1.39, 95%CI 0.54-2.23, P=0.001) were found in norepinephrine group
      compared with dopamine group. However, there were no significant differences on
      the effect of mean artery pressure (SMD=0.64, 95%CI -1.09-2.38, P=0.47), oxygen
      delivery (SMD=-0.54, 95%CI -1.50-0.42, P=0.27), oxygen consumption(SMD=-0.49,
      95%CI -1.37-0.39, P=0.27) and lactic acid (SMD=-0.24, 95%CI -0.90-0.42, P=0.48)
      between these two vasopressors. CONCLUSIONS: Norepinephrine is associated with an
      improved hemodynamics and decreased mortality compared with dopamine in septic
      shock patients.

PMID- 24021038
TI  - [Effects of cyclic stretch on the induction of the transdifferentiation in human
      lung epithelial cells].
AB  - OBJECTIVE: To investigate the effect of mechanical stretch induced epithelial
      mesenchymal transition in human lung epithelial cells BEAS-2B in vitro. METHODS:
      The human lung epithelial cells BEAS-2B were subjected to cyclic stretch by the
      FX-5000T system at 0.33 Hz of 10% or 20% elongation for 24, 48 and 72 hours
      respectively. The morphologic changes were observed by microscopy. The mRNA and
      protein expressions of E-cadherin, Cytokeratin-8 (CK-8), alpha-smooth muscle
      actin (alpha-SMA) and Vimentin were evaluated by immunofluorescence before and
      after mechanical stretch and fluorescent quantitation reverse transcription
      polymerase chain reaction (qRT-PCR). RESULTS: (1) When stretch by 20% elongation
      for 48 hours, the morphological changes in BEAS-2B cells from cobblestone-like
      structure to elongated shape and obviously when stretch for up to 72 hours, while
      10% elongation showed no significant morphological changes comparing to control.
      (2) Decreasing E-cadherin and CK-8 protein expression was associated with
      increased immunostaining for alpha-SMA protein at 72 hours after 20% mechanical
      stretch. (3) Expression of E-cadherin mRNA was decreased to 0.388+/-0.056 and
      0.247+/-0.064 after 20% mechanical stretch for 48 hours and 72 hours compared
      with control without stretch (set 1, both P<0.05), expression of CK-8 mRNA was
      decreased to 0.436+/-0.060 at 72 hours after 20% mechanical stretch (P<0.01),
      alpha-SMA mRNA was increased to 1.437+/-0.267 (48 hours) and 1.261+/-0.247 (72
      hours) after 20% mechanical stretch (both P<0.05), and Vimentin mRNA was
      increased to 1.679+/-0.172 (48 hours) after 20% mechanical stretch (P<0.05).
      Expression of E-cadherin mRNA was decreased to 0.387+/-0.081 at 72 hours after
      10% mechanical stretch (P<0.05), Vimentin mRNA was increased to 1.688+/-0.179 at
      48 hours after 10% mechanical stretch while other markers showed no significant
      changes comparing with control. CONCLUSIONS: Excessive mechanical stretch could
      induce epithelial-mesenchymal transition in lung epithelial cells BEAS-2B in
      vitro.

PMID- 24021039
TI  - [Study of changes in extravascular lung water index of patients suffered from
      H7N9 avian influenza with acute respiratory distress syndrome].
AB  - OBJECTIVE: To analyze the characteristic of changes in extravascular lung water
      index (EVLWI) of H7N9 avian influenza patients who complicated with acute
      respiratory distress syndrome (ARDS), and to approach the relevance between EVLWI
      and severity, pulmonary oxygenation in patients with lung injury. METHODS: Four
      H7N9 avian influenza patients administered from April to June in 2013 in First
      Affiliated Hospital of Nanchang University were studied. The patients who
      suffered from severe ARDS were administered with low tide volume ventilation plus
      positive end-expiratory pressure (PEEP), namely protected ventilation strategy,
      with monitoring hemodynamic parameters and EVLWI through pulse-indicated
      continuous cardiac output (PiCCO) catheter. During ventilation, patients'
      parameters, such as PEEP, fraction of inspired oxygen (FiO2), arterial partial
      pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), cardiac index (CI),
      systemic vascular resistance index (SVRI), pulmonary vascular resistance index
      (PVRI), EVLWI, and central venous pressure (CVP) were collected. RESULTS: All 4
      H7N9 avian influenza patients were complicated with ARDS, 2 patients were
      classified to severe ARDS and administered with comprehensive therapies,
      specially protected ventilation strategy; ventilation duration was 9 days and 30
      days respectively, and PiCCO monitoring was 9 days and 21 days respectively.
      EVLWI of 2 patients on the 1st, 2nd, 3rd day was 10.0+/-3.2 ml/kg, 12.0+/-2.9
      ml/kg, 14.0+/-4.2 ml/kg, and 24.0+/-6.7 ml/kg, 24.0+/-6.1 ml/kg, 23.0+/-5.8
      ml/kg, respectively. As their conditions became better, patients' EVLWI decreased
      to 5.5+/-2.7 ml/kg and 7.0+/-3.0 ml/kg, respectively at weaning. PEEP and FiO2 of
      2 patients were down-regulated, PaO2/FiO2 increased to 334+/-64 mm Hg and 142+/
      53 mm Hg at weaning. However, no significant changes in CI, SVRI, PVRI and CVP in
      the 2 patients were observed. CONCLUSIONS: EVLWI increases when H7N9 avian
      influenza patients are complicated with severe ARDS. As the conditions get
      better, EVLWI returns to normal value gradually. There is relevance between the
      motive changes in EVLWI and severity of ARDS and pulmonary oxygenation.

PMID- 24021040
TI  - [Association between -1654C/T and -1641A/G gene polymorphism of protein C
      susceptibility and prognosis in severe sepsis].
AB  - OBJECTIVE: To approach the allele frequency and genotypic distribution of protein
      C (PC) gene polymorphism on the susceptivity and prognosis in severe sepsis
      patients. METHODS: Eighty patients with severe sepsis were enrolled. They were
      divided into survival group (n=47) and non-survival group (n=33) according to 28
      day prognosis. Seventy-two healthy volunteers were enrolled as controls. Allele
      specific polymerase chain reaction (AS-PCR) was used to analyze -1654C/T and 
      1641A/G site genotypes polymorphism of PC gene, fragments containing alleles was
      analyzed by using DNA sequencing. RESULTS: All the samples of the PC gene in the 
      1654C/T site had three kinds of genotypes: in 80 cases of severe sepsis group,
      there were 16 homozygous CC type, 44 heterozygous CT type, 20 homozygous TT type.
      In 72 cases of healthy control group, there were 17 CC type, 34 CT type, 21 TT
      type. The -1654C/T allele frequency and genotypic distribution in the patients
      with severe sepsis was not significantly different from those in the healthy
      control group, and no statistically significant difference was observed between
      the survival group and the non-survival group (all P>0.05). All the samples of
      the PC gene in the -1641A/G site had three kinds of genotypes: in 80 cases of
      severe sepsis group, there were 60 homozygous AA type, 12 heterozygous AG type, 8
      homozygous GG type. In 72 cases of healthy control group, there were 57 AA type,
      10 AG type, 5 GG type. No statistically significant difference was observed
      between severe sepsis group and healthy control group, the survival group and the
      non-survival group (all P>0.05) in -1641A/G allele frequency and genotypic
      distribution (all P>0.05). Three kinds of haploid, including -1654T/-1641A, 
      1654C/-1641A, and -1654C/-1641G were found except -1654T/-1641G. The frequency of
      haploid -1654C/-1641A was significant higher in non-survival group than that in
      the survival group [42.42% (14/33) vs. 21.28% (10/47), P=0.038]. CONCLUSIONS: The
      correlation between PC haploid -1654C/-1641A gene polymorphisms and prognosis of
      severe sepsis was found.

PMID- 24021041
TI  - [Procalcitonin change pattern in patients with septic shock and its relationship
      with prognosis].
AB  - OBJECTIVE: To investigate procalcitonin (PCT) change pattern in patients with
      septic shock and its relationship with prognosis. METHODS: Sixty-three septic
      shock patients were enrolled, and levels of PCT, C-reactive protein (CRP) as well
      as white blood cell (WBC) on 1st, 3rd, 5th,7th day after admission to intensive
      care unit (ICU) were checked. Patients were divided into survival group and death
      group according to 28-day survival result. Differences in parameters between two
      groups were compared. The change regulation of parameters along with in-hospital
      period and its relationship with prognosis were analyzed by multilevel linear
      model. RESULTS: There were 41 patients in survival group and 22 patients in death
      group. PCT and CRP level decreased in survival group with time dependency
      pattern, while death group increased. The PCT at 3, 5, 7 days after admission to
      ICU in death group were significantly higher than those in survivors (3 days:
      8.7+/-3.7 MUg/L vs. 5.6+/-1.7 MUg/L, 5 days: 10.3+/-1.3 MUg/L vs. 4.8+/-2.3
      MUg/L, 7 days: 12.7+/-2.3 MUg/L vs. 0.8+/-0.3 MUg/L, P<0.05 or P<0.01), and CRP
      at 5 days and 7 days was significantly higher than those in survival group (5
      days: 447+/-63 mg/L vs. 355+/-91 mg/L, 7 days: 439+/-45 mg/L vs. 364+/-63 mg/L,
      both P<0.05). Two groups of WBC did not change significantly, and there were no
      statistical significance difference at each time point between the two groups.
      What's more, the effect analysis results showed that there were significant
      changes in PCT as ICU day prolonged (F=10.91, P= 0.00), and there was a
      significant difference between the survivor and the dead (F=7.58, P=0.00), while
      CRP changed only with ICU stays (F=4.17, P=0.03). CONCLUSIONS: Compared with CRP
      and WBC, PCT had higher sensitivity in predicting prognosis, sustainable
      elevation of PCT level indicates poor prognosis, serum PCT can be used as one of
      indexes predicting prognosis of septic shock.

PMID- 24021042
TI  - [Analysis of risk factors on prognosis of Acinetobacter baumannii bloodstream
      infection].
AB  - OBJECTIVE: To explore the risk factors on prognosis of Acinetobacter baumannii
      bloodstream infection. METHODS: Clinical data from 78 patients with Acinetobacter
      baumannii bloodstream infection hospitalized in First Affiliated Hospital of
      Nanjing Medical University from January 2010 to November 2012 were analyzed
      retrospectively. According to the 28-day prognosis after admission, the patients
      were divided into non-survivors (n=40) and survivors (n=38). Data on demographic
      and clinical characteristics, wards, underlying diseases, treatments, invasive
      medical procedures, bacterial resistance to antibiotics, and acute physiology and
      chronic health evaluation II (APACHEII) score in the beginning were collected.
      The index as an independent risk factor of mortality was demonstrated by
      multivariate logistic regression analysis. The predictor value was concluded by
      comparing area under the receiver operating characteristic curve (ROC curve) of
      each index. RESULTS: Risk factors of mortality of Acinetobacter baumannii
      bloodstream infection goes as following, including intensive care unit
      admission[ICU, odds ratio (OR)=12.9,95% confidence interval (95%CI) 2.4-63.5,
      P=0.001], trachea intubation or tracheostomy (OR=6.2, 95%CI 1.5-30.4, P=0.023),
      invasive mechanical ventilation (OR=5.1, 95%CI 1.4-22.6, P=0.042), invasive
      medical procedure besides central venous catheter (including thoracentesis, bone
      marrow puncture, lumbar puncture, catheterization, bronchoalveolar lavage with
      bronchofibroscope, arteriovenous fistula plastic operation, OR=8.4, 95%CI 1.7
      37.8, P=0.011), APACHEII score >=19 in the beginning (OR=35.4, 95%CI 3.8-318.6,
      P=0.001). With respect to APACHE II score>= 19 as mortality cut-off point, an
      area under the receiver operating curve of 0.938 was statistically significant
      (P<0.05), with sensitivity 76.2% and specificity 94.1%. The relationship between
      prognosis and antibiotic resistance did not have statistically significance.
      CONCLUSIONS: Invasive medical procedures and treatments were associated with
      increased mortality of patients with Acinetobacter baumannii bloodstream
      infection. A strong predictor of adverse outcome in such conditions was APACHEII
      score >=19.

PMID- 24021043
TI  - [The clinical research of nystatin in prevention of invasive fungal infections in
      patients on mechanical ventilation in intensive care unit].
AB  - OBJECTIVE: To observe the effect of nystatin on incidence of invasive fungal
      infections (IFI) and the prognosis of mechanically ventilated critically ill
      patients. METHODS: A prospective study was conducted. Critical ill patients
      admitted to Department of Critical Care Medicine of Jiangxi Provincial People's
      Hospital from May 1st, 2012 to April 30th, 2013 needing mechanical ventilation
      were enrolled. The patients were randomly divided into two groups by envelope
      method. Patients in the nystatin group were administered nystatin 1000 kU three
      times a day via the gastric tube; and patients in the control group were given
      gastrointestinal prokinetic drug as placebo. The specimens were collected every 3
      days throughout the ICU stay (T0, T3, T6, T9), the strain distribution was
      observed, and the corrected colonization index (CCI) of all patients were
      calculated. The incidence of candidemia and 28-day mortality as well as the
      duration of stay in ICU and hospital were also recorded. RESULTS: A total of 874
      strains were isolated from 124 patients, of which Candida albicans accounted for
      57.6% (503/874). The most frequently colonized body sites were oropharyngeal
      site,account for 35.6% (311/874). The CCI of the nystatin group were lower than
      those of the control group at T6 and T9 [T6: 0.19+/-0.10 vs. 0.39+/-0.15, T9:
      0.00 (0.10) vs. 0.45 (0.30), all P<0.05]. The incidence of candidemia in the
      nystatin group was slightly lower than that in control group [0.5% (3/60) vs.
      7.8% (5/64), P>0.05]. The mortality in the nystatin group was lower than that in
      control group [18.3% (11/60) vs. 34.4% (22/64), P<0.05]. ICU day in the nystatin
      group was shorter than that in the control group (days: 9.56+/-3.47 vs. 11.89+/
      6.32, P<0.05). However,hospital day was similar in the two groups (days: 18.35+/
      7.42 vs. 20.58+/-8.77, P>0.05). CONCLUSIONS: Nystatin might reduce the
      colonization of Candida albicans and was associated with shorter ICU day.

PMID- 24021044
TI  - [Treatment study of hospital acquired pneumonia by optimizing dosing regimen of
      piperacillin/tazobactam:prolonged vs. regular infusion].
AB  - OBJECTIVE: To observe the serum concentration and evaluate clinical efficacy of
      piperacillin/tazobactam (TZP) prolonged infusion time in treatment of hospital
      acquired pneumonia (HAP). METHODS: Fifty HAP patients admitted to intensive care
      unit (ICU) from March 1 to October 31, 2012 were enrolled. The bacterial drug
      sensitivity results showed that the minimum inhibitory concentration (MIC) of TZP
      was 8 mg/L or 16 mg/L. According to completely randomized grouping method, the
      patients were divided into treatment group (n=25) and control group (n=25). The
      therapeutic regimen in control group was TZP 4.5 g, in regular infusion every 6
      hours and finished in 30 minutes; the treatment group was TZP 4.5 g, in prolonged
      infusion every 6 hours by using infusion pump for continuous intravenous infusion
      3 hours. Acute physiology and chronic health evaluation II(APACHEII) score,
      clinical pulmonary infection score (CPIS) and procalcitonin (PCT) level were
      compared between the two groups 3 days after treatment. The treatment success
      rate, remedial treatment rate, antibiotic costs were recorded in both groups.
      Blood specimen was collected at 0.5, 1, 2, 3, 4, 6 hours at the beginning of
      administration, and the blood drug concentration of piperacillin and tazobactam
      was determined using ultra performance liquid chromatography-tandem mass
      spectrometry (UPLC-MS). RESULTS: The PCT (2.16+/-0.17 MUg/L vs. 4.77+/-0.25
      MUg/L), CPIS score(6.21+/-1.14 MUg/L vs. 6.92+/-1.35 MUg/L) and remedial
      treatment rate (12.0% vs. 52.0%) of the treatment group were significantly lower
      than those of the control group after administration for 3 days (P<0.05 or
      P<0.01), and APACHEII score was slightly lower than that in control group
      (21.38+/-7.37 vs. 22.15+/-5.46, P>0.05). After active remedial treatment, there
      were no significant difference in the treatment success rate (88.0% vs. 80.0%)
      and relapse rate (4.2% vs. 7.7%) between treatment group and control group (both
      P>0.05). But the antibiotic costs in treatment group were significantly lower
      than that of control group (4330.38+/-1087.24 Yuan vs. 5506.15+/-1361.73 Yuan,
      P<0.01). The treatment course of antibacterials in treatment group was
      significantly shorter than that in control group (6.00+/-1.05 days vs. 8.20+/
      1.03 days, P<0.01). The infection by Pseudomonas aeruginosa, Escherichia coli and
      Klebsiella pneumoniae was monitored, TZP serum concentration administrated at 0.5
      6 hours in the treatment group was higher than MIC, but in the control group, TZP
      blood concentration was lower than MIC after administration for 2-3 hours. In
      treatment group, the percentage of duration of blood drug level higher than MIC
      account for dosing interval (%T>MIC) was 86.82%, while in the control group, the
      %T>MIC was 42.84%. CONCLUSIONS: TZP prolonged the infusion time dosing regimens
      using in Gram negative bacteria induced by high MIC value of HAP have more stable
      plasma concentration, curative clinical effect and reduce the cost of treatment.

PMID- 24021045
TI  - [Effects of cyclic stretch on expression of cytokines and intercellular adhesion
      molecule-1 in human pulmonary artery endothelial cell].
AB  - OBJECTIVE: To observe the effects of cyclic stretch on expression of cytokines
      and adhesion molecules in human pulmonary artery endothelial cells (HPAECs),
      herein to provide a theoretical basis to ventilator-induced lung injury (VILI).
      METHODS: HPAECs were subjected to cyclic stretch by the Flexcell FX-5000T system
      at 0.5 Hz of 10% or 20% elongation for 3, 6, 12, 24 hours respectively. The mRNA
      and protein expression of interleukin (IL-6, IL-8), monocyte chemotactic protein
      1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) was determined by
      fluorescent quantitation reverse transcription-polymerase chain reaction (qRT
      PCR), enzyme linked immunosorbent assay (ELISA) or Western blotting. RESULTS:
      Increasing the stretch force, the mRNA and protein expression of IL-8, MCP-1,
      ICAM-1 were up regulated with increasing stretch time. Compared with the control
      (set 1), after 20% cyclic stretch for 24 hours, IL-8 mRNA expression was up
      regulated to 1.58+/-0.10, MCP-1 mRNA expression was up regulated to 2.85+/-0.52,
      and ICAM-1 mRNA expression was up regulated to 1.90+/-0.14 (all P<0.05). Compared
      with control group, after 20% cyclic stretch for 24 hours, the protein expression
      of IL-8 and MCP-1 in HPAEC was significantly increased (IL-8: 3401.08+/-439.60
      ng/L vs. 1422.60+/-66.98 ng/L, MCP-1: 1117.64+/-237.54 ng/L vs. 307.88+/-80.84
      ng/L, both P<0.05), ICAM-1 protein expression was up regulated to 2.15+/-0.40
      (P<0.05), while the expression of IL-6 mRNA and protein had no statistic
      difference compared with control group. CONCLUSIONS: Cyclic stretch enhanced the
      expression of IL-8, MCP-1 and ICAM-1 in an intensity-dependent fashion, so it may
      be involved in the pathogenesis of lung injury induced by mechanical ventilation.

PMID- 24021046
TI  - [Association of traumatic severity with change in lymphocyte subsets in the early
      stage after trauma].
AB  - OBJECTIVE: To investigate the association of traumatic severity with changes in
      lymphocyte subsets in the early stage after trauma. METHODS: Sixty-three male
      patients admitted within 4 hours after trauma were enrolled. According to injury
      severity score (ISS), the patients were divided into two groups: mild trauma
      group (ISS<16, n=35) and severe trauma group (ISS>=16, n=28). At admission, the
      patients peripheral blood were extracted to detect T lymphocytes subsets, blood
      routine test, blood biochemical and arterial blood gas analysis which were used
      to calculate the acute physiology and chronic health evaluation II (APACHEII)
      scores. The correlation of lymphocyte subsets and ISS score, and the correlation
      of lymphocyte subsets and APACHEII score were both analyzed statistically.
      Another 20 cases of healthy male adults were enrolled as the control group.
      RESULTS: Compared with the healthy control group, CD3(+) T cell contents in blood
      were decreased obviously in mild trauma group and severe trauma group (0.648+/
      0.112, 0.647+/-0.110 vs. 0.708+/-0.082, both P<0.05); CD4(+) T cells contents in
      severe group were decreased significantly (0.317+/-0.086 vs. 0.389+/-0.064,
      P<0.05), and natural killer (NK) cells were significantly increased (0.217+/
      0.107 vs. 0.158+/-0.068, P<0.05). B cells content in severe group was decreased
      significantly than that of mild group (0.114+/-0.060 vs. 0.155+/-0.075, P<0.05).
      There were no significant difference in CD8(+) and CD4/CD8 ratio among the
      healthy control group, mild trauma group and severe trauma group (CD8(+): 0.260+/
      0.074, 0.260+/-0.091, 0.271+/-0.105; CD4/CD8 ratio: 1.69+/-0.75, 1.56+/-0.83,
      1.34+/-0.65, all P>0.05). Except that there were negative correlation between
      CD3(+) T cells and the ISS scores (r=-0.42, P=0.03), the other lymphocyte subsets
      showed no correlation with the ISS scores and the APACHEII scores (mild trauma
      group with ISS scores: CD3(+) r=-0.10, CD4(+) r=-0.31, CD8(+) r=0.18, B cells
      r=0.20, NK cells r=-0.04; mild trauma group with APACHEII scores: CD3(+) r=0.04,
      CD4(+) r=-0.07, CD8(+) r=0.06, B cells r=-0.10, NK cells r=0.05, severe trauma
      group with ISS scores: CD4(+) r=-0.12, CD8(+) r=-0.17, B cells r=0.02, NK cells
      r=0.31,all P>0.05;severe trauma group with APACHEII scores:CD3(+) r=-0.24, CD4(+)
      r=0.11, CD8(+) r=-0.26, B cells r=0.15, NK cells r=0.08, all P>0.05).
      CONCLUSIONS: CD3(+) and CD4(+) T cells decreased and NK cells increased
      significantly in blood in the early stage after severe trauma. CD3(+) T cells are
      independent indexes which reflect body injury. Therefore, it is necessary to
      monitor the changes of immune cells dynamically after severe trauma.

PMID- 24021047
TI  - The correlation study on antimicrobial resistance and biofilm related genes in
      clinical isolates of Acinetobacter baumannii.
AB  - In recent years, the proportion of nosocomial infections caused by Acinetobacter
      baumannii (Ab) strains has increased significantly, and its resistance to
      antibiotics is rising. The resistance mechanisms of Ab are complex, which include
      the integron formation, inactivating or deactivating enzyme, outer membrane
      permeability, biofilm formation, drug exocytosis mechanism and so on. The biofilm
      formation by bacteria leads to high resistance and immune evasion ability. The
      aim of this study is to investigate the resistance and distribution patterns of
      Ab isolates, and the biofilm formation related genes in Ab isolates in our
      hospital.

PMID- 24021048
TI  - [Clinical evaluation of right ventricular function in chronic obstructive
      pulmonary disease patients with Tei index combined with brain natriuretic peptide
      ].

PMID- 24021049
TI  - [Observation of anti-virus therapy in critically ill patients infected with avian
      influenza A (H7N9) virus].

PMID- 24021050
TI  - [Treatment understanding of human infection with swine Streptococcus: a case
      report].

PMID- 24021051
TI  - [Research progress of focal adhesion kinase in acute lung injury].

PMID- 24021052
TI  - [The progress in research of soluble cluster of differentiation antigen-14].

PMID- 24021053
TI  - [Resuscitation care to a patient with cardiac arrest in seed implantation
      process].

PMID- 24021054
TI  - Secondary care intervals before and after the introduction of urgent referral
      guidelines for suspected cancer in Denmark: a comparative before-after study.
AB  - BACKGROUND: Urgent referral for suspected cancer was implemented in Denmark on 1
      April 2008 to reduce the secondary care interval (i.e. the time interval from the
      general practitioner's first referral of a patient to secondary health care until
      treatment is initiated). However, knowledge about the association between the
      secondary care interval and urgent referral remains scarce. The aim of this study
      was to analyse how the secondary care interval changed after the introduction of
      urgent referral. METHODS: This was a retrospective population-based study of
      6,518 incident cancer patients based on questionnaire data from the patients'
      GPs. Analyses were stratified with patients discharged from Vejle Hospital in one
      stratum and patients from other hospitals in another because Vejle Hospital
      initiated urgent referrals several years prior to the national implementation.
      Further, analyses were stratified according to symptom presentation and whether
      or not the GP referred the patient on suspicion of cancer. Symptom presentation
      was defined as with or without alarm symptoms based on GP interpretation of early
      symptoms. RESULTS: The median secondary care interval decreased after the
      introduction of urgent referral. Patients discharged from Vejle Hospital tended
      to have shorter secondary care intervals than patients discharged from other
      hospitals. The strongest effect was seen in patients with alarm symptoms and
      those who were referred by their GP on suspicion of cancer. Breast cancer
      patients from Vejle Hospital experienced an even shorter secondary care interval
      after the national introduction of urgent referrals. CONCLUSION: Urgent referral
      had a positive effect on the secondary care interval, and Vejle Hospital
      remarkably managed to shorten the intervals even further. This finding indicates
      that the shorter secondary care intervals not only result from the urgent
      referral guidelines, but also involve other factors.

PMID- 24021055
TI  - Immunosenescence is associated with human cytomegalovirus and shortened telomeres
      in type I bipolar disorder.
AB  - OBJECTIVE: Bipolar disorder (BD) has been associated with persistent low-grade
      inflammation and premature cell senescence, as shown by reduced telomere length
      (TL). The human cytomegalovirus (CMV) has increasingly been implicated in
      accelerated immunosenescence in aging studies. Here, we compared CMV serology and
      its relationships with cell senescence markers, including TL and lymphocyte
      subsets, in patients with type I BD and healthy controls. METHODS: Twenty-two
      euthymic female patients with BD type I and 17 age-matched healthy controls were
      selected for the study. A sample of blood was collected and mononuclear cells and
      DNA were isolated and TL measured. CMV immunoglobulin M (IgM) and IgG titers were
      measured using chemiluminescent assays. Lymphocyte subsets [T, natural killer
      (NK) and NKT] were phenotyped by flow cytometry. RESULTS: Individuals with BD had
      shorter TLs but higher CMV IgG levels than controls (both p < 0.01). CMV IgG
      level was inversely correlated with TL. None of the subjects showed IgM
      reactivity for CMV, excluding acute viral infection. CMV IgG level was associated
      with expansion of senescent CD8+CD28- T cells and NK cells, which are involved in
      viral control. CONCLUSIONS: These data support the hypothesis of accelerated
      aging in BD, as shown by shortened telomeres, higher seropositivity for CMV, and
      expansion of senescent T cells.

PMID- 24021056
TI  - Effects of pH and fermentative substrate on ruminal metabolism of fatty acids
      during short-term in vitro incubation.
AB  - The ruminal biohydrogenation of c9,c12-18:2 can be affected by the fibre/starch
      ratio of the diet and the ruminal pH. The objectives of this study were to
      examine independently in vitro the effects of fermentation substrate (hay vs.
      corn starch) and buffer pH (6 vs. 7) on the biohydrogenation of c9,c12-18:2
      carried out by grape seed oil, focusing on its t11 and t10 pathways, using 6-h
      ruminal incubations. The experimental design was a 2 * 2 factorial arrangement.
      Fermentation substrate and pH affected the C18 fatty acid balance in incubated
      media, but few interactions were observed. Compared with starch, hay as the
      fermentation substrate favoured the production of 18:0 (*2.3), all trans-18:1
      isomers (*12.6) and CLA (*6.1), except c9,t11-CLA, and the disappearance of
      unsaturated C18 fatty acids, but decreased the production of odd and branched
      chain fatty acids. Compared with pH 6 buffer, pH 7 buffer resulted in higher
      c9,c12-18:2 disappearance and CLA production. For c9,t11-CLA, an interaction was
      noticed between the two factors, leading to the highest production in cultures
      incubated on hay with the 7 pH buffer. Compared with starch, hay as fermentation
      substrate favoured the activity of t11 producers, which are fibrolytic bacteria,
      and the production of t10 isomers, possibly due to the presence of potential t10
      producers in hay. Low pH resulted in a decreased t11 isomers production and in a
      slightly increased t10 isomers production, probably due to a modulation of
      enzymatic or bacterial activity. 

PMID- 24021057
TI  - Dental maturation in children with the syndrome of crouzon and apert.
AB  - Purpose : Developing teeth are used to assess maturity and estimate age in a
      number of disciplines. The purpose of this investigation was to study the dental
      maturation in children with Crouzon or Apert syndrome compared with nonsyndromic
      controls. Patients and Methods : Records of 40 children with Crouzon syndrome (18
      boys and 22 girls, aged 4.0 to 17.9 years) and 28 children with Apert syndrome
      (10 boys and 18 girls, aged 3.9 to 15.1 years) were referred to the Department of
      Orthodontics, Cleft Palate Team and Craniofacial Team, Erasmus MC-Sophia. Data
      from syndromic children were compared with data from 451 nonsyndromic children
      (225 boys and 226 girls, aged 2.9 to 16.9 years). From panoramic radiographs,
      dental maturation was determined for patients with Crouzon and Apert syndromes
      and compared with data collected from control children. Logistic functions were
      constructed for dental maturation over time for syndromes and gender. Results :
      Statistically significant gender differences in dental maturation scores were
      found for girls with Crouzon (P < .05) and Apert syndrome (P < .05). Patients
      with Apert syndrome demonstrated a significantly delayed dental maturation (P <
      .05), while patients with Crouzon syndrome showed a nonsignificant delay.
      Conclusions : Dental maturation in patients with Apert syndrome was more delayed
      than in patients with Crouzon syndrome. The delay of tooth formation in patients
      with Crouzon or Apert syndrome suggests a possible common genetic association. 

PMID- 24021058
TI  - Clinical results and pump analysis of the Gyro pump for long-term extracorporeal
      life support.
AB  - Rescuing patients in severe cardiac failure with extracorporeal support remains
      challenging. The Gyro pump is a centrifugal blood pump and was now used for
      cardiopulmonary bypass, although it was originally developed for long-term
      cardiac assist. Little is known about clinical experiences using this pump. Here,
      we report on the clinical results of long-term extracorporeal life support for
      over 4 days using the Gyro pump with Excelung, a hollow fiber oxygenator coated
      with silicone and heparin. Seven patients underwent extracorporeal life support
      with 15 pump and oxygenator combinations. Gyro and Excelung were used for
      venoarterial extracorporeal support in six patients and for right ventricular
      support in one patient. Patient characteristics, pump driving conditions, and
      blood chemistry were obtained retrospectively. All pumps were subsequently
      disassembled and examined macroscopically, with 6 of 15 pumps also examined by
      scanning electron microscopy (SEM). The patient mortality rate was 57.1%. Mean
      duration of support was 10.5 +/- 7.2 days per pump and oxygenator combination.
      Lactate dehydrogenase and aspartate aminotransferase were generally maintained
      below 1000 and 100 IU/L, respectively, after the first 4 days of pump driving.
      Thrombi were found in two pumps, one used without anticoagulation and the other
      driven at a very slow rotational speed. SEM revealed no wear in the male bearings
      and very low wear and deformation (0.02 +/- 0.03 mm) in the female bearings. The
      combination of Gyro and Excelung may be applicable for long-term biventricular
      and right ventricular support, although proper anticoagulation should be
      administrated to avoid thrombus formation inside the pump.

PMID- 24021059
TI  - A mutual activation loop between breast cancer cells and myeloid-derived
      suppressor cells facilitates spontaneous metastasis through IL-6 trans-signaling
      in a murine model.
AB  - INTRODUCTION: Tumor cell interactions with the microenvironment, especially those
      of bone-marrow-derived myeloid cells, are important in various aspects of tumor
      metastasis. Myeloid-derived suppressor cells (MDSCs) have been suggested to
      constitute tumor-favoring microenvironments. In this study, we elucidated a novel
      mechanism by which the MDSCs can mediate spontaneous distant metastasis of breast
      cancer cells. METHODS: Murine breast cancer cells, 4T1 and EMT6, were
      orthotopically grafted into the mammary fat pads of syngeneic BALB/c mice.
      CD11b(+)Gr-1(+) MDSCs in the spleen, liver, lung and primary tumor mass were
      analyzed. To evaluate the role of MDSCs in the distant metastasis, MDSCs were
      depleted or reconstituted in tumor-bearing mice. To evaluate whether MDSCs in the
      metastasizing tumor microenvironment affect breast cancer cell behavior, MDSCs
      and cancer cells were co-cultivated. To investigate the role of MDSCs in in vivo
      metastasis, we blocked the interactions between MDSCs and cancer cells. RESULTS:
      Using a murine breast cancer cell model, we showed that murine breast cancer
      cells with high IL-6 expression recruited more MDSCs and that the metastasizing
      capacity of cancer cells paralleled MDSC recruitment in tumor-bearing mice.
      Metastasizing, but not non-metastasizing, tumor-derived factors induced MDSCs to
      increase IL-6 production and full activation of recruited MDSCs occurred in the
      primary tumor site and metastatic organ in the vicinity of metastasizing cancer
      cells, but not in lymphoid organs. In addition, tumor-expanded MDSCs expressed
      Adam-family proteases, which facilitated shedding of IL-6 receptor, thereby
      contributing to breast cancer cell invasiveness and distant metastasis through IL
      6 trans-signaling. The critical role of IL-6 trans-signaling was confirmed in
      both the afferent and efferent pathways of metastasis. CONCLUSION: In this study,
      we showed that metastasizing cancer cells induced higher MDSCs infiltration and
      prompted them to secret exaggerated IL-6 as well as soluble IL-6Ra, which, in
      turn, triggered a persistent increase of pSTAT3 in tumor cells. This potential
      tumor-MDSC axis involving IL-6 trans-signaling directly affected breast cancer
      cell aggressiveness, leading to spontaneous metastasis.

PMID- 24021060
TI  - [Medical practice and clinical research: keys to generate knowledge and improve
      care].
AB  - The increased quality in medical care may be immediately accomplished if clinical
      research is integrated into daily clinical practice. In the generation of medical
      knowledge are four steps: an unanswered question awakened from clinical practice,
      the critical analysis of specialized literature, the development of a research
      protocol, and, finally, the publication of outcomes. Decision making and
      continuous training are becoming part of an effective strategy of medical
      attention improvement.

PMID- 24021061
TI  - [Excessive use of foreign references].

PMID- 24021063
TI  - [Gaffes and pearls of wisdom].

PMID- 24021062
TI  - [Linguistic considerations from a reader].

PMID- 24021064
TI  - [Prognosis in pediatric traumatic brain injury. A dynamic cohort study].
AB  - BACKGROUND: traumatic brain injury is a main cause of hospital admission and
      death in children. Our objective was to identify prognostic factors of pediatric
      traumatic brain injury. METHODS: this was a dynamic cohort study of traumatic
      brain injury with 6 months follow-up. The exposition was: mild or moderate/severe
      traumatic brain injury, searching for prognosis (morbidity-mortality and
      decreased Glasgow scale). Relative risk and logistic regression was estimated for
      prognostic factors. RESULTS: we evaluated 440 patients with mild traumatic brain
      injury and 98 with moderate/severe traumatic brain injury. Morbidity for mild
      traumatic brain injury was 1 %; for moderate/severe traumatic brain injury, 5 %.
      There were no deaths. Prognostic factors for moderate/severe traumatic brain
      injury were associated injuries (RR = 133), fractures (RR = 60), street accidents
      (RR = 17), night time accidents (RR = 2.3) and weekend accidents (RR = 2).
      Decreased Glasgow scale was found in 9 %, having as prognostic factors: visible
      injuries (RR = 3), grown-up supervision (RR = 2.5) and time of progress (RR =
      1.6). CONCLUSIONS: there should be a prognosis established based on kinetic
      energy of the injury and not only with Glasgow Scale.

PMID- 24021065
TI  - [Activities after school time and obesity in children. Influence of family and
      neighborhood environment].
AB  - BACKGROUND: elementary school children spend little time at the school in Mexico.
      The aim was to investigate the activities after school time in children and to
      determine the presence of overweight and obesity. METHODS: one hundred and
      seventy two children of both sexes were included. They belonged to the first and
      second grade of an official primary school from a marginalized zone. Somatometry
      was obtained and the type of physical practice and motifs for no practice
      physical activity were investigated. Descriptive statistics were applied.
      RESULTS: the frequency of underweight was 12.1 %, overweight 19 %, and obesity
      18.5 %. Sedentary activities like watching television and playing video games
      were the most common registered, whereas sports were the lowest physical activity
      practiced, especially in girls. The parents' lack of time, low family income, and
      the scarcity of safe spaces where children can play and practice physical
      activity or sports were the most related factors. CONCLUSIONS: poverty and
      insecurity of the neighborhoods influence the outside activities in after school
      time. The high frequency of underweight, overweight and obesity in school
      children were associated to the lack of physical activity.

PMID- 24021067
TI  - [How do the obese persons perceive their overall health?].
AB  - BACKGROUND: the purpose was to investigate how the obese person perceives their
      health in different areas of their life. METHODS: the SF-36 instrument, which
      measures various dimensions (social and physical functioning, mental and physical
      health, bodily pain, limitations due to physical and/or emotional problems,
      vitality and general health), was applied to 224 patients. It was analyzed
      whether there were differences between gender, which were channeled to the
      treatment (surgical and nonsurgical) and the degree of obesity (overweight,
      obesity and morbid obesity). A descriptive analysis, Student t test, Anova and
      Tukey t test were used. RESULTS: significant differences (p < 0.05) were found in
      some dimensions, like tendency to feel tired, exhausted and feeling that their
      health has been and will continue to deterioration. Women had a worse social and
      emotional functioning than men; patients with gastric bypass reported more
      fatigue than patients with gastric band; in regards to the degree of obesity,
      those who had morbid obesity showed less physical functioning, more pain and
      worse overall health than those who were just obese. CONCLUSIONS: the perception
      of the obese patients was that their health had deteriorated. Women were more
      affected in social and emotional functioning than men.

PMID- 24021066
TI  - [Silicosis and industrial bronchitis by exposure to silica powders and cement].
AB  - OBJECTIVE: to identify the association between the exposure of workers to
      inorganic dust in a quarry and a cement factory and pulmonary diseases. METHODS:
      a transverse study on data from 32 quarry workers (QWs) and 57 cement production
      line workers (CFWs) to inorganic-dust exposure was performed. Pulmonary function
      tests and chest X ray were done in both groups. RESULTS: there were differences
      between QWs and the CFWs; QWs were younger, shorter and thinner. The number of
      sick individuals might be considered significantly different, showing a smaller
      proportion on the cement production line. The quarry workers have been on the
      company for a shorter period of time and, in the end, they present more serious
      pulmonary problems with an average of 3 years working. CONCLUSIONS: the amount of
      free-silica that is managed on the quarry affects the workers in some way, even
      when literature states that the evolution of industrial bronchitis and silicosis
      have a period development of approximately 10 years.

PMID- 24021068
TI  - [Septal alcohol ablation in patients with hypertrophic cardiomyopathy].
AB  - OBJECTIVE: to know the clinical and hemodynamic course in septal obstructive
      hypertrophic cardiomyopathy (SOHC) after alcohol ablation. METHODS: this was an
      observational, longitudinal study, including 21 patients with SOHC with
      functional class of the New York Heart Association (CF-NYHA) refractory to
      treatment and/or = 30 mm Hg gradient at rest or = 60 mm Hg provoked, or have
      systolic anterior motion or mitral incompetence (MI) > grade II by
      echocardiography. RESULTS: average age was 50 +/- 16 years, males 38.1 %, females
      61.9 %; symptoms: angina 42.9 %, dyspnea 85.7 %, syncope 23.8 %. Pre-ablation CF
      NYHA was III and IV in 61.9 %; after a year follow-up all of them were class I
      II. Pre-ablation, after and one year later, interventricle septum measures were
      22.7 +/- 4.9 and 20.7 +/- 3.1 mm; left ventricular ejection fraction was 65.5 +/-
      7 %, 62.2 % +/- 6.5 % and 68.7 +/- 6.2 %; the output gradient of the left
      ventricle were 106.9 +/- 29.9, 44.6 +/- 24.3 and 22.0 +/- 5.7 mm Hg. Pre-ablation
      MI grade-III and IV were 33.3 % and 47.6 %; after a year it was grade-0, 52.4 %,
      grade-I 28.6 %, grade-II, 19 %. There were no hospital mortality. CONCLUSIONS:
      the alcohol septal ablation in SOHC patients had a high success treatment with a
      low complication rate.

PMID- 24021069
TI  - [Proceeding memory in Alzheimer's disease].
AB  - Procedural learning can acquire or develop skills through performance and
      repetition of a task unconsciously or unintentionally. Procedural skills are
      considered as the cornerstone in the neuropsychological rehabilitation to promote
      the autonomy of patients with brain damage, as those with Alzheimer's disease.
      This review presents data about procedural skills in Alzheimer's disease. Over
      the past three decades, we have found 40 articles studying various procedural
      skills in the Alzheimer's disease: motor, perceptual-motor, cognitive, perceptual
      cognitive and those developed through serial reaction-time paradigm. We analyzed
      every study evaluating a procedural skill, indicating the used task and
      preservation or no preservation of procedural learning. Overall, most of the
      papers published describe conservation of learning procedures or relatively
      conserved in Alzheimer's disease, which could be used to promote patient
      autonomy. 

PMID- 24021070
TI  - [Clinical research XVI. Differences between medians with the Mann-Whitney U
      test].
AB  - If you want to prove that there are differences between two groups with
      quantitative variables with non-normal distribution, the Mann-Whitney U test is
      used. This test is opposite of the Student t test that uses quantitative
      variables with a normal distribution. If you want to compare three or more
      nonrelated groups, the Kruskal-Wallis test is applied. When two related samples
      are compared, the Wilcoxon test is the best option (a before and after maneuver
      comparison); when three related samples are compared, the Friedman test is used.
      These tests correspond to the parametric opposing paired t test and ANOVA,
      respectively. 

PMID- 24021071
TI  - [Pap test used for detection of cellular changes associated with human
      papillomavirus].
AB  - Human papilloma virus can infect any mucous of the body and can cause cancer of
      the uterine cervix. This suggests recommending the Papanicolaou smear combined
      with a test for detection of human papillomavirus with a frequency interval of 3
      years, since it grants greater information and fidelity to the result. The
      detection studies should begin at the age of 21 years and should stop at 65 years
      age. Until recently specific treatments did not exist to treat human papilloma
      virus, but recently some drugs that have demonstrated good effectiveness in
      curing the infection of human papilloma virus. One example is glycirrhicinic
      acid, which has demonstrated fewer adverse effects, as well as the possibility
      that its systemic employment allows treatment of lesions that are difficult to
      approach. The medical recommendations should be in constant revision, since a
      clinical trial can modify the interpretation of what is necessary to
      individualize each patient's treatment.

PMID- 24021072
TI  - [Opportunistic bacteria and microbial flora in children with leukemia and
      neutropenic enterocolitis].
AB  - OBJECTIVE: to determine the prevalence of opportunistic microorganisms and
      microbial flora in neutropenic enterocolitis in oncohematological pediatric
      patients. METHODS: a prospective and observational study was done. Patients with
      diagnosis of acute leukemia and neutropenia were included. Stool cultures were
      taken to identify microorganisms and microbial flora. A chi(2) test with Yates
      corrections and Fisher exact test were used in the statistical analysis. RESULTS:
      21 patients were included (12 male, 57.1 %). The stool cultures showed that 68 %
      of microorganisms were Gram-negative. The presence of microorganisms Gram
      positive was 20 %, 6 % for Candida sp.; 3 % for Cryptosporidium sp.; and in 3 %
      were acid fast bacilli. Staphylococcus epidermidis, Enterobacter sp., and
      Escherichia coli were presented in pure culture. No association was found between
      Gram-positive and Gram-negative microorganisms with age, white cell count or pure
      or mixed cultures. CONCLUSIONS: although Gram-negative microorganisms were the
      most frequent, Gram-positive and other microorganisms that are not detected
      habitually in feces culture were isolated.

PMID- 24021073
TI  - [Burnout syndrome among family physicians].
AB  - BACKGROUND: burnout syndrome is a state of physical and emotional exhaustion that
      can occur among workers who interact directly with others. This could affect job
      performance. The objective was to determine the prevalence of this syndrome and
      its associated factors among family physicians. METHODS: a cross-sectional survey
      applying the Maslach Burnout Inventory was conducted in a selected convenience
      non-probability sampling of family physicians. Central tendency and dispersion
      measures were used in determining the prevalence of burnout syndrome; the
      associated factors were analysed by chi(2) test. RESULTS: there were 59 cases of
      burnout syndrome, 36 had involvement in a single component, 15 in 2 and 8 were
      affected in 3 components; we observed that 35 % of positive cases reported doing
      an average of 10 extra shifts a month (p = 0.013). Having a second job was
      associated with positive cases of burnout syndrome. CONCLUSIONS: the results are
      consistent with similar studies. Working extra shifts or having a second job were
      the related factors most associated to this syndrome.

PMID- 24021074
TI  - [Clinical impact of social marketing strategy on breast cancer detection].
AB  - OBJECTIVE: to prove the impact of social marketing strategies in breast cancer
      detection, taking as a parameter the number of mammographies performed. METHODS:
      quasi-experimental research, before and after. Sixty-nine physicians in charge of
      medical consultation and fourteen nurses were studied for a period of seven
      months, applying social marketing strategies. The total of mammographies were
      analyzed using Wilcoxon rank-sum test (p < 0.05). RESULTS: morning schedule:
      medical consultation with a base of 1.5 mammographies monthly by physician
      office, first and second month after intervention of 2.45 (p = 0.007); nurses
      with a base of 2.14 mammographies, first and second month after intervention were
      3.25 (p = 0.007) and 3.28 (p = 0.000), respectively. Afternoon schedule: medical
      consultation, base were 0.47, first and second month after intervention were 2.38
      (p = 0.000) and 2.35 (p = 0.000) respectively; nurses with a base of 0.85, first
      and second month 2.79 (p = 0.000) and 3.91 (p = 0.000), respectively.
      CONCLUSIONS: social marketing proved to be an adequate strategy, which has an
      impact on the clinical practice of both physicians and nurses.

PMID- 24021075
TI  - [Small infundibulectomy versus ventriculotomy in tetralogy of Fallot].
AB  - BACKGROUND: the surgical correction of tetralogy of Fallot (TOF) is standardized
      on the way to close the septal defect, but differs in the way of expanding the
      right ventricular outflow tract (RVOT). The aim was to compare the early
      postoperative clinical course of the RVOT obstruction enlargement in classical
      ventriculotomy technique and the small infundibulectomy (SI). METHODS: We
      analyzed the database of the pediatric heart surgery service from 2008 to 2011.
      Patients with non-complex TOF undergoing complete correction by classical
      ventriculotomy or SI were selected. Anova, chi(2) and Fisher statistical test
      were applied. RESULTS: the data included 47 patients, 55 % (26) male, mean age 43
      months (6-172), classical ventriculotomy was performed in 61.7 % (29). This group
      had higher peak levels of lactate (9.07 versus 6.8 mmol/L) p = 0049, and greater
      magnitude in the index bleeding/kg in the first 12 hours (39.1 versus 20.3 mL/kg)
      p = 0.016. Death occurred in 9 cases (31.03 %) versus one (5.6 %) in the SI group
      with p = 0.037; complications exclusive as acute renal failure, hemopneumothorax,
      pneumonia, permanent AV-block and multiple organ failure were observed.
      CONCLUSIONS: morbidity and mortality was higher in classical ventriculotomy group
      in comparison with SI. This is possibly associated with higher blood volume.

PMID- 24021076
TI  - [Influenza-like illness. Therapeutic experience in family medicine].
AB  - BACKGROUND: influenza is a highly contagious respiratory disease. Surveillance in
      Mexico is based on the detection of Influenza-Like Illness (ILI) and antiviral
      treatment should begin within 48 hours to avoid the main complication, pneumonia.
      The aim was to describe the experience of treatment of ILI in a family medicine
      unit. METHODS: a descriptive study included patients presented to the emergency
      room with ILI (38 degrees C fever, headache and cough accompanied by other
      symptoms). We reviewed the reporting formats of Influenza. To follow up, we
      contacted them by telephone. Data are expressed as mean +/- standard deviation.
      RESULTS: there were 537 patients attended with diagnosis of upper airway
      infection, 1.3 % met criteria for ILI. 85.7 % were men. The mean age was 18 +/-
      24.21 years. The patients were seen in a mean time of 19.14 hours after the
      symptoms have started; 100 % of the patients received treatment with oseltamivir
      and zanamivir; 14.3 % developed pneumonia. All the patients recovered without
      concomitant disease or complications. CONCLUSIONS: The use of a protocol in
      patients with influenza in a family medicine unit led an early diagnosis and
      treatment that favored the patients' health restoration.

PMID- 24021077
TI  - [Food consumption in and around the school].
AB  - BACKGROUND: elementary school students usually stay in school 4.5 hours a day in
      Mexico. The main food consumption is outside school. The objective was to explore
      behaviors on food consumption beyond the school environment. METHODS: descriptive
      trial that included 173 children, both sexes, from public elementary school in
      Mexico City. Eating habits were obtained through questionnaire and anthropometric
      characteristics from physical measurement. RESULTS: participants reported to
      consume soft drinks and canned juices at high frequency and quantity (80 %) and
      low consumption of animal foods. They also eat industrialized dairy products with
      high caloric content and low in protein. Moreover, 30 % of children eat 4 or 5
      times a day, whereas 10 % eat one or two times a day. These results were
      associated with the somatometric characteristics of the children, 37.6 % of whom
      presented as overweight or obese while 12 % were underweight. CONCLUSIONS: it is
      necessary that health education involves teachers, parents and children in
      programs for obesity prevention with the objective of increasing healthy
      behaviors.

PMID- 24021078
TI  - [Mucha-Habermann disease and orthotopic heart transplant. Case report].
AB  - BACKGROUND: Mucha-Habermann disease is a cutaneous clinical manifestation of
      unknown etiology that frequently appears in young patients. The aim was to
      present Mucha-Habermann disease that occurred in an old man who had a heart
      transplant. CLINICAL CASE: a 62 year-old male, heart transplant recipient, who
      four years after that transplantation procedure presented with papular lesions in
      neck, thoracic members of which extended to all body surfaces and that evolved
      vesicles and pustular lesions. A skin biopsy was performed and Mucha-Habermann
      disease was diagnosed. The patient was treated with steroids and antimicrobial
      therapy with favorable response. After two years there are no skin lesions.
      CONCLUSIONS: Mucha-Habermann disease is a low frequency disease and it requires
      skin biopsy to confirm diagnose. This is an uncommon case due to the age and kind
      of patient.

PMID- 24021079
TI  - [Cerebral artery infarction presented as an unusual complication of acute middle
      otitis].
AB  - BACKGROUND: acute otitis media is a frequent disease in the pediatric age. About
      2 % of all cases develop intracranial complications such as meningitis. The
      cerebral infarction originates meningitis and usually occurs in the venous
      system. The presence of a cerebral artery infarction secondary to acute otitis
      media is a rare cause described in the literature. CLINICAL CASE: a girl of 12
      months who presented a febrile syndrome due to acute otitis media and mental
      confusion. On physical examination, she appeared sleepy with anisocoria,
      mydriasis in the right eye and left hemiparesis. The computed tomography
      examination showed extensive cerebral artery infarction. The patient's parents
      refused the proposed surgical treatment and the girl died 48 hours later.
      CONCLUSIONS: regardless of the current technological advances, the clinical
      prognosis of cerebral infarction associated with acute otitis media is bad. The
      focused neurological signs and progressive clinical deterioration should raise
      suspicion that antimicrobial therapy is not effective.

PMID- 24021080
TI  - [Multicentric hyaline vascular Castleman's disease. A POEMS type variant].
AB  - BACKGROUND: Castleman's disease is an atypical lymphoproliferative disorder which
      may be compatible with paraneoplastic manifestations of POEMS syndrome. CLINICAL
      CASE: a 53 year old man with a history of type 2 diabetes, hypothyroidism and
      Addison's disease presented with numbness and weakness in limbs, dyspnea, skin
      hardening, Raynaud's phenomenon, weight loss and fatigue. A physical exam showed
      tachypnea, generalized cutaneous hyperpigmentation and skin hardening of
      extremities, muscle weakness, hypoesthesia and hyporeflexia. Laboratory showed
      hyperprolactinemia, low testosterone, hypothyroidism and Addison's disease.
      Electrophoresis of proteins showed polyclonal hypergammaglobulinemia.
      Somatosensory evoked potentials reported peripheral neuropathy and severe axonal
      polyneuropathy by electromyography. Chest X-rays showed bilateral reticular
      infiltrates and mediastinal widening. An echocardiogram displayed moderate
      pulmonary hypertension. Skin biopsy had no evidence of scleroderma. CT reported
      axillar, mediastinal and retroperitoneal nodes. The mediastinal lesion biopsy
      reported hyaline vascular Castleman's disease, multicentric variety. He was
      treated with rituximab. CONCLUSIONS: the case meet criteria for multicentric
      hyaline vascular Castleman's disease, POEMS variant, treated with rituximab.

PMID- 24021081
TI  - [Epidermoid neoplasm of the fourth ventricle. Report of two cases].
AB  - BACKGROUND: epidermoid neoplasm (EN) accounts for 1 % of whole intracranial
      neoplasms. Usually, it is found at the cerebello-pontine angle and the location
      in the fourth ventricle (FV) is rare. The aim was to report two cases of EN of
      the FV. CLINICAL CASES: case 1: a female 22 year old presented with an intense
      headache with a history of 3 months. At the hospital entry, symptoms and signs of
      high intracranial pressure were found. Tomography images showed hydrocephalus
      with high pressure in the FV. She was treated with a shunt from ventricular to
      peritoneal cavity. After that an encapsulated neoplasm was drawn. It had a
      pearled aspect. The histology report showed an EN originating in the FV. Case 2:
      a female 44 year old with a history of five years of dizziness; three years
      before admission she presented intermittent diplopia and disophagia. At the
      hospital admission the patient presented paresis of the 6th and 7th cranial
      nerve. The tomography and the magnetic resonance studies showed a mass in the FV.
      The neoplasm was extirpated. CONCLUSIONS: the EN of the FV is an infrequent
      benign lesion. Magnetic resonance is the standard diagnostic study, but it could
      lead to confusion with neurocisticercosis. The extirpation and the treatment of
      the hydrocephalus are indicated.

PMID- 24021082
TI  - [Clinical practice guideline. Traumatic urethral stenosis in males].
AB  - The incidence of urethral stenosis in Mexico had not been documented. At the
      Centro Medico Nacional La Raza, during the year 2010, 629 patients with urethral
      stenosis were attended as outpatient consultation: 85 % with previous urethral
      stenosis and 15 % with urethral treatment complication. Urethral stenosis is a
      chronic illness, with multiple etiological origins and the handling is
      controversial. It has a great negative impact for the patients and the recurrence
      reaches 85 %. The treatment consisted of an invasive approach (urethral
      dilations, endoscopy procedure) and open surgery (urethroplasty). The World
      Health Organization and World Alliance take the world challenge about the urinary
      tract infections associated with the attention of patients, focused on urethral
      stenosis. The objective of the following clinical guide is to offer to the health
      professional a clinical tool for making decisions in the handling of the hardship
      or masculine urethral stenosis, based on the best available evidence, carrying
      out in systematized form with bibliographical research using validated terms of
      the MeSH: urethral structures, in the databases Trip database, PubMed, Guideline
      Clearinghouse, Cochrane Library and Ovid. 

PMID- 24021083
TI  - Aerobic soil biotransformation of 6:2 fluorotelomer iodide.
AB  - 6:2 FTI [F(CF2)6CH2CH2I] is a principal industrial raw material used to
      manufacture 6:2 FTOH [F(CF2)6CH2CH2OH] and 6:2 FTOH-based products and could
      enter aerobic environments from possible industrial emissions where it is
      manufactured. This is the first study to assess 6:2 FTI aerobic soil
      biotransformation, quantify transformation products, and elucidate its
      biotransformation pathways. 6:2 FTI biotransformation led to 6:2 FTOH as a key
      intermediate, which was subsequently biotransformed to other significant
      transformation products, including PFPeA [F(CF2)4COOH, 20 mol % at day 91], 5:3
      acid [F(CF2)5CH2CH2COOH, 16 mol %], PFHxA [F(CF2)5COOH, 3.8 mol %], and 4:3 acid
      [F(CF2)4CH2CH2COOH, 3.0 mol %]. 6:2 FTI biotransformation also led to a
      significant level of PFHpA [F(CF2)6COOH, 16 mol % at day 91], perhaps via another
      putative intermediate, 6:2 FTUI [F(CF2)6CH ? CHI], whose molecular identity and
      further biotransformation were not verified because of the lack of an authentic
      standard. Total recovery of the aforementioned per- and polyfluorocarboxylates
      accounted for 59 mol % of initially applied 6:2 FTI by day 91, in comparison to
      56 mol % when soil was dosed with 6:2 FTOH, which did not lead to PFHpA. Thus,
      were 6:2 FTI to be released from its manufacture and undergo soil microbial
      biotransformation, it could form PFPeA, PFHpA, PFHxA, 5:3 acid, and 4:3 acid in
      the environment.

PMID- 24021085
TI  - Proceedings of the Canadian Society for Exercise Physiology Annual General
      Meeting - Extreme Human Physiology: From Pathology to Performance.

PMID- 24021084
TI  - Today's students: tomorrow's teachers.

PMID- 24021086
TI  - Rapid ultrasensitive single particle surface-enhanced Raman spectroscopy using
      metallic nanopores.
AB  - Nanopore sensors embedded within thin dielectric membranes have been gaining
      significant interest due to their single molecule sensitivity and compatibility
      of detecting a large range of analytes, from DNA and proteins, to small molecules
      and particles. Building on this concept we utilize a metallic Au solid-state
      membrane to translocate and rapidly detect single Au nanoparticles (NPs)
      functionalized with 589 dye molecules using surface-enhanced resonance Raman
      spectroscopy (SERRS). We show that, due to the plasmonic coupling between the Au
      metallic nanopore surface and the NP, signal intensities are enhanced when
      probing analyte molecules bound to the NP surface. Although not single molecule,
      this nanopore sensing scheme benefits from the ability of SERRS to provide rich
      vibrational information on the analyte, improving on current nanopore-based
      electrical and optical detection techniques. We show that the full vibrational
      spectrum of the analyte can be detected with ultrahigh spectral sensitivity and a
      rapid temporal resolution of 880 MUs. 

PMID- 24021087
TI  - The application of mechanical aerosol delivery systems in an in vitro model of
      mechanically ventilated neonates.
AB  - Delivery of medication to the neonatal lung using current methods is inefficient.
      Aerosols offer one way to improve delivery to small airways. In this in vitro
      work, aerosol delivery by using a micropump or a rotary valve has been evaluated
      in a model of the neonatal setting with a pressurised metered dose inhaler plus
      spacer outside of the inspiratory limb. Drug depositions were assessed by
      spectrophotometric analyses. Drug lung deposition was increased by adjusting the
      rotary valve for co-ordination between the inhalation and aerosol delivery, but
      this intermittent mode decreased the aerosol delivery by using the micropump.
      Also, decreasing the volume of spacer decreased drug deposition in test lungs by
      using the micropump system. At the optimum conditions, the rotary valve aerosol
      delivery system delivered 3.68+/-0.91% of the Qvar nominal dose to the test
      lungs, and this was 2.34+/-0.01% for the micropump system. In conclusion, the
      rotary valve aerosol delivery system provided higher amounts of drug particles to
      the test lungs compared to the micropump system. The advantages of these methods
      were that the humidity in the ventilation circuit did not affect the aerosol
      particles in the spacer. Further optimisation is required to improve aerosol
      deposition in the test lungs. The article has also a short section of recent
      patents relevant to aerosol delivery. 

PMID- 24021088
TI  - Levenshtein error-correcting barcodes for multiplexed DNA sequencing.
AB  - BACKGROUND: High-throughput sequencing technologies are improving in quality,
      capacity and costs, providing versatile applications in DNA and RNA research. For
      small genomes or fraction of larger genomes, DNA samples can be mixed and loaded
      together on the same sequencing track. This so-called multiplexing approach
      relies on a specific DNA tag or barcode that is attached to the sequencing or
      amplification primer and hence appears at the beginning of the sequence in every
      read. After sequencing, each sample read is identified on the basis of the
      respective barcode sequence.Alterations of DNA barcodes during synthesis, primer
      ligation, DNA amplification, or sequencing may lead to incorrect sample
      identification unless the error is revealed and corrected. This can be
      accomplished by implementing error correcting algorithms and codes. This
      barcoding strategy increases the total number of correctly identified samples,
      thus improving overall sequencing efficiency. Two popular sets of error
      correcting codes are Hamming codes and Levenshtein codes. RESULT: Levenshtein
      codes operate only on words of known length. Since a DNA sequence with an
      embedded barcode is essentially one continuous long word, application of the
      classical Levenshtein algorithm is problematic. In this paper we demonstrate the
      decreased error correction capability of Levenshtein codes in a DNA context and
      suggest an adaptation of Levenshtein codes that is proven of efficiently
      correcting nucleotide errors in DNA sequences. In our adaption we take the DNA
      context into account and redefine the word length whenever an insertion or
      deletion is revealed. In simulations we show the superior error correction
      capability of the new method compared to traditional Levenshtein and Hamming
      based codes in the presence of multiple errors. CONCLUSION: We present an
      adaptation of Levenshtein codes to DNA contexts capable of correction of a pre
      defined number of insertion, deletion, and substitution mutations. Our improved
      method is additionally capable of recovering the new length of the corrupted
      codeword and of correcting on average more random mutations than traditional
      Levenshtein or Hamming codes.As part of this work we prepared software for the
      flexible generation of DNA codes based on our new approach. To adapt codes to
      specific experimental conditions, the user can customize sequence filtering, the
      number of correctable mutations and barcode length for highest performance.

PMID- 24021091
TI  - Dangerous liaisons between detergents and membrane proteins. The case of
      mitochondrial uncoupling protein 2.
AB  - The extraction of membrane proteins from their native environment by detergents
      is central to their biophysical characterization. Recent studies have emphasized
      that detergents may perturb the structure locally and modify the dynamics of
      membrane proteins. However, it remains challenging to determine whether these
      perturbations are negligible or could be responsible for misfolded conformations,
      altering the protein's function. In this work, we propose an original strategy
      combining functional studies and molecular simulations to address the
      physiological relevance of membrane protein structures obtained in the presence
      of detergents. We apply our strategy to a structure of isoform 2 of an uncoupling
      protein (UCP2) binding an inhibitor recently obtained in dodecylphosphocholine
      detergent micelles. Although this structure shares common traits with the ADP/ATP
      carrier, a member of the same protein family, its functional and biological
      significance remains to be addressed. In the present investigation, we
      demonstrate how dodecylphosphocholine severely alters the structure as well as
      the function of UCPs. The proposed original strategy opens new vistas for probing
      the physiological relevance of three-dimensional structures of membrane proteins
      obtained in non-native environments. 

PMID- 24021090
TI  - Prevalence and predictors of anal incontinence during pregnancy and 1 year after
      delivery: a prospective cohort study.
AB  - OBJECTIVE: To evaluate the prevalence and predictors of anal incontinence (AI) in
      late pregnancy and 1 year after delivery. DESIGN: Prospective population-based
      cohort study. SETTING: Two maternity units in Norway 2009-2010. POPULATION:
      Primiparae aged 18 years or over. METHODS: Primiparae answered questions on the
      St. Mark's score about AI during the last 4 weeks of pregnancy. One year later,
      the same questionnaires were distributed by postal mail. Socio-economic and
      delivery-related data were obtained from hospital records. MAIN OUTCOME MEASURES:
      Self-reported AI. RESULTS: Answers on AI in late pregnancy were obtained from
      1571 women, and 1030 responded 1 year later. Twenty-four per cent experienced one
      and 4.7% experienced three or more AI symptoms in late pregnancy. One year later,
      this was reduced to 19% and 2.2%, respectively. Multivariate logistic regression
      analyses were applied. Formed and loose stool incontinence were strongly
      associated at both time points. The main predictor of AI 1 year after delivery
      was AI in late pregnancy. Obstetric anal sphincter injury increased the risk of
      incontinence of stool and flatus (odds ratio [OR], 4.1; 95% confidence interval
      [CI], 1.7-9.6) after delivery. Urgency was associated with greater age (OR, 1.8;
      95% CI, 1.0-3.3) and operative delivery (OR, 2.0; 95% CI, 1.3-2.9). CONCLUSION:
      One in four primiparae experienced AI in late pregnancy. One year later, still
      one in five suffered from incontinence. Sphincter injury predicted incontinence
      of stool and flatus, whereas greater age and operative delivery predicted
      urgency. The identification and adequate follow-up of pregnant women with AI may
      reduce AI after delivery.

PMID- 24021092
TI  - PRDM16 rs2651899 variant is a risk factor for Chinese common migraine patients.
AB  - OBJECTIVE: Recent genome-wide association studies (GWAS) have identified 3 loci
      in or near PRDM16 (1p36.32, rs2651899), LRP1 (12q13.3, rs11172113) and TRPM8
      (2q37.1, rs10166942) in the population-based Women's Genome Health Study (WGHS)
      of migraine, and 2 loci in or near TRPM8 and LRP1 were repeated in European GWAS
      study. To evaluate whether the same variants are related to migraine in Chinese
      population, we investigated migraine with aura (MA) and migraine without aura
      (MO) patients of Chinese Han ethnicity in mainland China. METHODS: A case-control
      study in a cohort of 207 migraine cases and 205 ethnically matched controls was
      conducted by using the dual-color fluorescence resonance energy transfer (FRET)
      probes analysis. RESULTS: The genotypes of all polymorphisms in 2 groups followed
      the Hardy-Weinberg equilibrium. We found significant differences in allele
      distribution of rs2651899 variant in PRDM16 between MO patients and control
      subjects (P = .049, OR = 1.335, 95%CI 1.001-1.782), and there were no difference
      between MA patients and controls in the frequency of genotype and allele. Also,
      no significant differences in genotypic and allelic distributions between MA or
      MO patients and controls were observed in the polymorphisms of rs10166942 of
      TRPM8 and rs11172113 of LRP1, and there was no significant difference comparing
      male with female in all loci. CONCLUSION: Our data suggested that rs2651899
      variant in PRDM16 plays a potential role in Chinese MO migraine susceptibility,
      and gender may not play a role.

PMID- 24021093
TI  - Stem cell-like side populations in esophageal cancer: a source of chemotherapy
      resistance and metastases.
AB  - Dye-effluxing side population (SP) cells can be resistant to chemotherapy and are
      thought to resemble cancer stem cells. We characterized the relevance of the SP
      subpopulation in esophageal cancer cell lines and their relation to chemotherapy
      resistance and metastasis. The SP subpopulation was detected using Hoechst 33342
      staining in five esophageal cancer cell lines OE19, OE21, OE33, PT1590, and
      LN1590. CTx-resistant cell lines were developed after long-term exposure to 5
      fluorouracil (5-FU) and cisplatin and validated by analysis of resistance
      markers, thymidylate synthase and ERCC1. While neither LN1590 nor PT1590 had
      detectable SP cells, OE19, OE21, and OE33 cells were found to contain varying
      levels of SP cells. With increasing duration of 5-FU or cisplatin therapy, the SP
      subpopulation substantially emerged in PT1590 and LN1590. OE19-SP cells displayed
      significant higher tumorigenicity than OE19- non-SP (NSP) cells after
      subcutaneous tumor cell injection in vivo. SP cells isolated from OE19 and OE19/5
      FUres were subsequently analyzed by an epithelial-to-mesenchymal transition (EMT)
      polymerase chain reaction array. Interestingly, the SP fraction of OE19/5-FUres
      showed a dramatic upregulation of EMT-related genes compared to the SP fraction
      of OE19. Our results provide evidence that (1) the proportion of SP cells is
      different in esophageal cancer, (2) SP cells exhibit stem cell properties and are
      associated to chemotherapy resistance, and (3) long-term CTx selects for SP cells
      with an upregulated EMT gene profile, which might be the source of systemic
      disease relapse. Further investigations are necessary to ideally target these EMT
      associated SP cells in esophageal cancer. 

PMID- 24021094
TI  - Effectiveness of a cognitive behavioural therapy-based rehabilitation programme
      (Progressive Goal Attainment Program) for patients who are work-disabled due to
      back pain: study protocol for a multicentre randomised controlled trial.
AB  - BACKGROUND: Psychologically informed rehabilitation programmes such as the
      Progressive Goal Attainment Program (PGAP) have the potential to address pain
      related disability by targeting known psychological factors that inhibit
      rehabilitation progress. However, no randomised controlled trials of this
      intervention exist and it has not been evaluated in the Irish health service
      context. Our objective was to evaluate the clinical efficacy and cost
      effectiveness of the PGAP in a multicentre randomised controlled trial with
      patients who are work-disabled due to back pain. METHODS AND DESIGN: Adult
      patients (ages 18 years and older) with nonmalignant back pain who are work
      disabled because of chronic pain and not involved in litigation in relation to
      their pain were invited to take part. Patients were those who show at least one
      elevated psychosocial risk factor (above the 50th percentile) on pain disability,
      fear-based activity avoidance, fatigue, depression or pain catastrophizing.
      Following screening, patients are randomised equally to the intervention or
      control condition within each of the seven trial locations. Patients allocated to
      the control condition receive usual medical care only. Patients allocated to the
      PGAP intervention condition attend a maximum of 10 weekly individual sessions of
      structured active rehabilitation in addition to usual care. Sessions are
      delivered by a clinical psychologist and focus on graded activity, goal-setting,
      pacing activity and cognitive-behavioural therapy techniques to address possible
      barriers to rehabilitation.The primary analysis will be based on the amount of
      change on the Roland Morris Disability Questionnaire posttreatment. We will also
      measure changes in work status, pain intensity, catastrophizing, depression, fear
      avoidance and fatigue. Outcome measures are collected at baseline, posttreatment
      and 12-month follow-up. Health-related resource use is also collected pre- and
      posttreatment and at 12-month follow-up to evaluate cost-effectiveness.
      DISCUSSION: This study will be the first randomized controlled trial of the PGAP
      in chronic pain patients and will provide important information about the
      clinical and cost effectiveness of the programme as well as its feasibility in
      the context of the Irish health service. TRIAL REGISTRATION: Current Controlled
      Trials: ISRCTN61650533.

PMID- 24021095
TI  - Molecular taxonomy of the two Leishmania vectors Lutzomyia umbratilis and
      Lutzomyia anduzei (Diptera: Psychodidae) from the Brazilian Amazon.
AB  - BACKGROUND: Lutzomyia umbratilis (a probable species complex) is the main vector
      of Leishmania guyanensis in the northern region of Brazil. Lutzomyia anduzei has
      been implicated as a secondary vector of this parasite. These species are closely
      related and exhibit high morphological similarity in the adult stage; therefore,
      they have been wrongly identified, both in the past and in the present. This
      shows the need for employing integrated taxonomy. METHODS: With the aim of
      gathering information on the molecular taxonomy and evolutionary relationships of
      these two vectors, 118 sequences of 663 base pairs (barcode region of the
      mitochondrial DNA cytochrome oxidase I - COI) were generated from 72 L.
      umbratilis and 46 L. anduzei individuals captured, respectively, in six and five
      localities of the Brazilian Amazon. The efficiency of the barcode region to
      differentiate the L. umbratilis lineages I and II was also evaluated. The data
      were analyzed using the pairwise genetic distances matrix and the Neighbor
      Joining (NJ) tree, both based on the Kimura Two Parameter (K2P) evolutionary
      model. RESULTS: The analyses resulted in 67 haplotypes: 32 for L. umbratilis and
      35 for L. anduzei. The mean intra-specific genetic distance was 0.008 (0.002 to
      0.010 for L. umbratilis; 0.008 to 0.014 for L. anduzei), whereas the mean
      interspecific genetic distance was 0.044 (0.041 to 0.046), supporting the
      barcoding gap. Between the L. umbratilis lineages I and II, it was 0.009 to
      0.010. The NJ tree analysis strongly supported monophyletic clades for both L.
      umbratilis and L. anduzei, whereas the L. umbratilis lineages I and II formed two
      poorly supported monophyletic subclades. CONCLUSIONS: The barcode region clearly
      separated the two species and may therefore constitute a valuable tool in the
      identification of the sand fly vectors of Leishmania in endemic leishmaniasis
      areas. However, the barcode region had not enough power to separate the two
      lineages of L. umbratilis, likely reflecting incipient species that have not yet
      reached the status of distinct species.

PMID- 24021098
TI  - Cloning and enhancing production of a detergent- and organic-solvent-resistant
      nattokinase from Bacillus subtilis VTCC-DVN-12-01 by using an eight-protease-gene
      deficient Bacillus subtilis WB800.
AB  - BACKGROUND: Nattokinases/Subtilisins (EC 3.4.21.62) belong to the second large
      family of serine proteases, which gain significant attention and play important
      role in many biotechnology processes. Thus, a number of nattokinases/subtilisins
      from various Bacillus species, especially from B. subtilis strains, extensively
      have been investigated to understand their biochemical and physical properties as
      well as to improve the production for industrial application. The purpose of this
      study was to clone a nattokinase gene from Bacillus subtilis strain VTCC-DVN-12
      01, enhance its production in B. subtilis WB800, which is deficient in eight
      extracellular proteases and characterize its physicochemical properties for
      potential application in organic synthesis and detergent production. RESULTS: A
      gene coding for the nattokinase (Nk) from B. subtilis strain VTCC-DVN-12-01
      consisted of an ORF of 1146 nucleotides, encoding a pre-pro-protein enzyme (30-aa
      pre-signal peptide, 76-aa pro-peptide and 275-aa mature protein with a predicted
      molecular mass of 27.7 kDa and pI 6.6). The nattokinase showed 98-99% identity
      with other nattokinases/subtilisins from B. subtilis strains in GenBank. Nk was
      expressed in B. subtilis WB800 under the control of acoA promoter at a high level
      of 600 mg protein per liter culture medium which is highest yield of proteins
      expressed in any extracellular-protease-deficient B. subtilis system till date.
      Nk was purified to homogeneity with 3.25 fold purification, a specific activity
      of 12.7 U/mg, and a recovery of 54.17%. The purified Nk was identified by MALDI
      TOF mass spectrometry through three peptides, which showed 100% identity to
      corresponding peptides of the B. subtilis nattokinase (CAC41625). An optimal
      activity for Nk was observed at 65  degrees C and pH 9. The nattokinase was
      stable at temperature up to 50  degrees C and in pH range of 5-11 and retained
      more than 85% of its initial activity after incubation for 1 h. Mg2+ activated Nk
      up to 162% of its activity. The addition of Triton X-100, Tween 20, and Tween 80
      showed an activation of Nk up to 141% of its initial activity but SDS strongly
      inhibited. The enzyme was highly resistant to organic solvents. CONCLUSIONS: Our
      findings demonstrated that an eight-protease-gene-deficient Bacillus subtilis
      WB800 could overproduce the nattokinase from B. subtilis VTCC-DVN-12-01. Due to
      high resistance to detergents and organic solvents of this nattokinase, it could
      be potentially applied in organic synthesis and detergent production.

PMID- 24021100
TI  - Motherhood and medical ethics: looking beyond conception and pregnancy.

PMID- 24021099
TI  - Cognitive and affective predictors of smoking after a sentinel health event.
AB  - OBJECTIVE: This study examined how smoking-related causal attributions, perceived
      illness severity, and event-related emotions relate to both intentions to quit
      and subsequent smoking behavior after an acute medical problem (sentinel event).
      METHODS: Three hundred and seventy-five patients were enrolled from 10 emergency
      departments (EDs) across the USA and followed for six months. Two saturated,
      manifest structural equation models were performed: one predicting quit attempts
      and the other predicting seven-day point prevalence abstinence at 14 days, three
      months, and six months after the index ED visit. Stage of change was regressed
      onto each of the other predictor variables (causal attribution, perceived illness
      severity, event-related emotions) and covariates, and tobacco cessation outcomes
      were regressed on all of the predictor variables and covariates. RESULTS: Non
      White race, baseline stage of change, and an interaction between causal
      attribution and event-related fear were the strongest predictors of quit attempt.
      In contrast, abstinence at six months was most strongly predicted by baseline
      stage of change and nicotine dependence. CONCLUSION: Predictors of smoking
      behavior after an acute medical illness are complex and dynamic. The relations
      vary depending on the outcome examined (quit attempts vs. abstinence), differ
      based on the time that has progressed since the event, and include significant
      interactions.

PMID- 24021101
TI  - Weighing risks and benefits of prescribing antidepressants during pregnancy.

PMID- 24021102
TI  - Induced lactation for the nongestating mother in a lesbian couple.

PMID- 24021103
TI  - Mentoring students about career and life.

PMID- 24021104
TI  - Whose hands? Global migration, elder care, and the mothers of others.

PMID- 24021105
TI  - Epigenetic inheritance and the moral responsibilities of mothers.

PMID- 24021106
TI  - Ferguson v. City of Charleston and criminalizing drug use during pregnancy.

PMID- 24021107
TI  - Mothers Matter: Ethics and Research during Pregnancy.

PMID- 24021108
TI  - Shackling and separation: motherhood in prison.

PMID- 24021109
TI  - The difference between science and technology in birth.

PMID- 24021110
TI  - Breast pumping.

PMID- 24021111
TI  - A life of mothering.

PMID- 24021112
TI  - The ghost of the schizophrenogenic mother.

PMID- 24021113
TI  - Different hydration patterns in the pores of AmtB and RhCG could determine their
      transport mechanisms.
AB  - The ammonium transporters of the Amt/Rh family facilitate the diffusion of
      ammonium across cellular membranes. Functional data suggest that Amt proteins,
      notably found in plants, transport the ammonium ion (NH4(+)), whereas human
      Rhesus (Rh) proteins transport ammonia (NH3). Comparison between the X-ray
      structures of the prokaryotic AmtB, assumed to be representative of Amt proteins,
      and the human RhCG reveals important differences at the level of their pore.
      Despite these important functional and structural differences between Amt and Rh
      proteins, studies of the AmtB transporter have led to the suggestion that
      proteins of both subfamilies work according to the same mechanism and transport
      ammonia. We performed molecular dynamics simulations of the AmtB and RhCG
      proteins under different water and ammonia occupancy states of their pore. Free
      energy calculations suggest that the probability of finding NH3 molecules in the
      pore of AmtB is negligible in comparison to finding water. The presence of water
      in the pore of AmtB could support the transport of proton. The pore lumen of RhCG
      is found to be more hydrophobic due to the presence of a phenylalanine conserved
      among Rh proteins. Simulations of RhCG also reveal that the signature histidine
      dyad is occasionally exposed to the extracellular bulk, which is never observed
      in AmtB. These different hydration patterns are consistent with the idea that Amt
      and Rh proteins are not functionally equivalent and that permeation takes place
      according to two distinct mechanisms. 

PMID- 24021114
TI  - What do journal editors want? ... and everything you wanted to know about the
      peer review process for journal publication.

PMID- 24021115
TI  - [Logical thinking on the large dosage of Statin in clinical implication].

PMID- 24021116
TI  - [Overview and analysis of research projects on miRNA in cardiovascular diseases
      funded by NSFC].

PMID- 24021117
TI  - [Consensus on emergency management of arrhythmias].

PMID- 24021118
TI  - [Catheter ablation of epicardial accessory pathway associated with coronary sinus
      musculature].
AB  - OBJECTIVE: To report the single-center clinical experience of catheter ablation
      of epicardial accessory pathway associated with coronary sinus musculature.
      METHODS: The data of 721 cases of left sided accessory pathway ablation were
      retrospectively analyzed. Ablation in the coronary sinus was performed in 17 (2.4
      %) cases [11 males, mean age (37 +/- 11) years]. RESULTS: Among the 17 cases, the
      accessory pathway was successfully ablated in middle cardiac vein and posterior
      lateral coronary sinus in 11 and 6 cases, respectively. Deverticulum of middle
      cardiac vein was seen in 2 cases. Mean time required to block the accessory
      pathway was (4.7 +/- 2.7) s. An accessory pathway potential could be recorded at
      the target site in 10 out of 17 patients (59%). During a mean (21 +/- 16) months
      follow up, only one patient experienced recurrence who was successfully cured by
      a second ablation session. No procedure related complication was reported.
      CONCLUSION: About 2.4% of left accessory pathway may have epicardial connection
      locating at middle cardiac vein or lateral part of the coronary sinus and require
      epicardial ablation. The epicardial ablation is safe and effective, warrants an
      excellent long-term results.

PMID- 24021119
TI  - [Radiofrequency catheter ablation of the premature ventricular contractions
      originating from His bundle region].
AB  - OBJECTIVE: To explore the electrocardiogram and 3-dimensional electroanatomic
      mapping features and radiofrequency catheter ablation efficacy of patients with
      premature ventricular contractions (PVCs ) originating from His bundle region.
      METHODS: Between February 2009 and February 2011, 10 consecutive patients ( 4
      male, aged from 19 to 59 years) who underwent ablation for frequent PVCs
      originating close to His bundle region in our department were included.
      Electroanatomic mapping of RVOT and ASC, ablation was performed with the 7F 4-mm
      tip ablation catheter. RESULTS: Among these 10 patients with PVCs originating
      from His bundle region, 6 originated from the RVOT, 1 from NCC and 3 from RCC.
      Eight patients showed LBBB morphology,1 patient with PVCs originated from RCC and
      1 patient with PVCs originated from NCC showed RBBB morphology. At the successful
      ablation sites, local ventricular activation v wave was detected 22-52 (32.6 +/-
      10.2) ms earlier than the QRS wave in the surface electrocardiogram. The distance
      between target and His bundle was 5.0-8.4(7.0 +/- 1.1)mm. Ablation was successful
      in all 10 patients without complications (PVCs < 500 beats/24 h post ablation).
      CONCLUSION: PVCs originating near the His bundle have similar
      electrocardiographic and electrophysiological characteristics for PVSc originated
      from the RVOT or ASC. Because of the close anatomical relationship between RVOT
      and ASC, it is necessary to mapping both RVOT and ASC to accurately identify the
      site of PVCs origin and to guild successful ablation.

PMID- 24021120
TI  - [Long term outcome of atrial fibrillation patients with KCNA5 and NPPA mutations
      post circumferential pulmonary vein ablation].
AB  - OBJECTIVE: The outcome of atrial fibrillation patients with genetic mutations
      post ablation was not well evaluated. METHODS AND RESULTS: Three atrial
      fibrillation patients with evidence of mutations in KCNA5 and NPPA post
      successful circumferential pulmonary vein ablation were included. Mutation in
      KCNA5 was found in one male patient with paroxysmal atrial fibrillation. He was
      free of atrial fibrillation post ablation after 46 months follow-up. Mutations in
      NPPA were found in two male patients with persistent atrial fibrillation and they
      were free from atrial fibrillation after 64 months and 38 months follow-up post
      circumferential pulmonary vein ablation, roof line and mitral isthmus line
      ablation. CONCLUSION: Satisfactory long term results are observed in atrial
      fibrillation patients with KCNA5 and NPPA mutations post circumferential
      pulmonary vein ablation.

PMID- 24021121
TI  - [Prevalence and risk factors of atrial fibrillation in hospitalized patients with
      chronic kidney disease].
AB  - OBJECTIVE: Atrial fibrillation (AF) is the most common sustained tachyarrhythmia
      in the general population. AF and Chronic Kidney Disease (CKD) share several
      common risk factors. We investigated the association between chronic kidney
      disease and risk of atrial fibrillation in hospitalized patients with CKD.
      METHODS: One thousand one hundred and sixty-eight patients [(63.3 +/- 14.2)
      years, 54.5% males] hospitalized CKD patients were included. AF was determined by
      electrocardiogram or medical history. The prevalence of atrial fibrillation was
      compared in CKD patients with various age, sex and glomerular filtration rate
      (eGFR). Binary logistic regression analysis was used to determine the risk
      factors of AF. RESULT: The mean eGFR was (22.2 +/- 19.7) ml . min(-1) . 1.73 m(
      2); eGFR was <= 45 ml . min(-1) . 1.73 m(-2) in 84.2% patients and 38.5% patients
      received hemodialysis. AF was present in 14.2% of the study population and 17.2%
      in patients >= 60 years old. Prevalence of AF was significantly higher in
      patients with eGFR <= 45 ml . min(-1) . 1.73 m(-2) compared patients with eGFR >
      45 ml . min(-1) . 1.73 m(-2) (15.8% vs. 5.4%, P < 0.001). Binary logistic
      regression analysis showed that age, body mass index (BMI), heart failure (HF),
      left atrial diameter (LAD), eGFR and dialysis were independent risk factors for
      AF. CONCLUSIONS: AF is much more frequent in CKD patients than in the general
      population. Age, BMI, HF, LAD, eGFR and dialysis are risk factors for AF in
      hospitalized patients with CKD.

PMID- 24021122
TI  - [Association between high-sensitivity C-reactive protein and contrast-induced
      nephropathy after primary percutaneous coronary intervention].
AB  - OBJECTIVE: To explore the association between high-sensitivity C-reactive protein
      (hs-CRP) and contrast-induced nephropathy (CIN) in patients with ST-segment
      elevated myocardial infarction (STEMI) undergoing percutaneous coronary
      intervention (PCI) . METHODS: A total of 220 STEMI patients undergoing primary
      PCI from Guangdong general hospital were recruited. Patients were divided into
      four groups according to the quartile of hs-CRP (Q1 group:hs-CRP < 6.26 mg/L,Q2
      group:6.26-14.44 mg/L, Q3 group:14.45-33.08 mg/L, Q4 group:hs-CRP > 33.08 mg/L) .
      Baseline data, CIN incidence and other in-hospital outcomes were compared among
      groups. CIN was defined as an increase in serum creatinine of more than 5 mg/L
      from baseline within 48-72 hours after contrast media exposure. Receiver operator
      characteristics (ROC) curves and multivariate logistic regression were used to
      assessed the correlation between hs-CRP and CIN. RESULTS: CIN occurred in 21
      (9.8%) patients. CIN incidence of hs-CRP quartitles were 1.8%(1/55), 1.8% (1/55),
      14.5% (8/55) and 20.0% (11/55) (P-trend < 0.01), respectively. In-hospital death
      (P-trend > 0.05) , required renal replace therapy (P-trend > 0.05) were similar
      among groups. ROC analysis revealed that the optimal cutoff value of hs-CRP to
      predict the onset of CIN was 16.85 mg/L (sensitivity: 81.0%, specificity: 61.8%,
      AUC: 0.748). Univariate logistic analysis showed that hs-CRP was strongly related
      with CIN incidence (OR = 6.88,95%CI:2.23-21.21, P < 0.01). Multivariate logistic
      regression analysis showed that after adjusting other traditional risk factors
      including female gender, anemia, ACEI/ARB use, IABP support, LVEF < 40%, age > 75
      years, baseline eGFR and diabetes, hs-CRP > 16.85 mg/L was still a significant
      independent predictor of CIN in patients with STEMI undergoing primary PCI.
      Additionally, age > 75 years (OR = 7.27,95%CI:1.85-28.63, P < 0.01), eGFR (OR =
      6.38,95% CI:1.48-27.41, P < 0.05) were also independent risk factors of CIN.
      CONCLUSIONS: hs-CRP is positively correlated with CIN incidence. STEMI patients
      with higher hs-CRP level post PCI is at higher risk of developing CIN.

PMID- 24021123
TI  - [Relationship between cholesteryl ester transfer protein gene -629C->A mutations
      with HDL-C levels and coronary heart disease].
AB  - OBJECTIVE: To investigate the relationship between the -629C/A polymorphism in
      the promoter region of the CETP gene, serum Levels, lipid metabolism, and
      coronary heart disease (CHD) among Tianjin Han Chinese population. METHODS: A
      hospital-based case-control study was conducted in Tianjin Chest Hospital from
      2010 October to 2011 October. The subjects underwent angiography were divided
      into a case group (n = 429) and a control group (n = 275). The CETP gene promoter
      polymorphism at position -629 was determined by restricted fragment length
      polymorphism using the polymerase chain reaction (PCR-RFLP) method.The serum CETP
      levels was determined by enzyme-linked immunosorbent assay (ELISA) method.
      RESULTS: (1)The lower frequency of -629A allele in Tianjin Han Chinese population
      was 0.408, significantly lower than that in other domestic and foreign
      populations (0.479-0.701, P < 0.05). (2) Variant AA genotype showed reduced CETP
      levels(P > 0.05) and higher HDL-C levels (P < 0.05), compared to wild CC
      genotype. (3) Although there was a negative trend correlation between serum CETP
      and HDL-C levels, it did not reach statistical significance(P > 0.05). (4)There
      were significant differences in the frequencies of CETP gene -629 genotype and
      allele between the two groups (P < 0.001),carries with CA/AA genotype and A
      allele showed higher risk of CHD, OR (95%CI) values were 4.627 (3.163-6.769),
      8.779 (4.799-16.059) and 3.173 (2.453-4.104) respectively. There was no
      relationship between CETP-629C/A polymorphism and coronary artery stenosis
      degree(chi(2) = 3.588, P = 0.166). CONCLUSION: The frequencies of CETP gene -629
      genotype and allele in the Tianjin Han Chinese population was significantly
      different from that in Other domestic and foreign populations. Variant AA
      genotype, which showed reduced CETP levels and higher HDL-C levels, is
      paradoxically associated with increased risk of CHD. Thus, CETP gene variation
      may affect coronary risk apart from the level of HDL-C.

PMID- 24021124
TI  - [Impact and potential mechanism of human alpha-defensin 1 on low-density
      lipoprotein oxidation ability of ECV304 cells].
AB  - OBJECTIVE: To explore the role and potential mechanism of human alpha-defensin 1
      (HNP-1) on low-density lipoprotein (LDL) oxidation ability of human endothelial
      cells (EVC304). METHODS: Post incubation with LDL for 3 h, the malondialdehyde
      (MDA) and protein carbonyl (PCO) were detected in untreated ECV304 (control) and
      in HNP-1 transfected ECV304 in the presence and absence of siRNA against HNP-1.
      Flow cytometry and fluorescence microscopy were used to detect the generation of
      oxygen free radical in the ECV304 which have been pretreated by LDL, LPS and HNP
      1, respectively. RESULT: Compared with control group, MDA level was significantly
      increased in HNP-1 transfected [(4.21 +/- 0.03) vs. (3.15 +/- 0.02) nmol/mg .
      pro] or in HNP-1 stimulated ECV304 cells [(14.49 +/- 1.10) vs. (9.47 +/- 1.18)
      nmol/mg . pro], which could be significantly downregulated by siRNA [(3.76 +/-
      0.48) vs. (4.54 +/- 0.28) nmol/mg.pro, all P < 0.05]. PCO was also significantly
      increased in HNP-1 transfected ECV304 cells. The levels of free radical were
      significantly increased in HNP-1 transfected or HNP-1 stimulated ECV304 cells.
      CONCLUSION: HNP-1 can enhance the LDL oxidation ability of human endothelial
      cells via promoting the generation of free radicals.

PMID- 24021125
TI  - [Feasibility of using intravascular loopless monopole antenna to image
      atherosclerotic plaque in a porcine model with 3.0 T magnetic resonance imaging].
AB  - OBJECTIVE: To investigate the feasibility of using intravascular loopless
      monopole antenna (ILMA) to image atherosclerosis plaque in a porcine model with
      3.0T magnetic resonance imaging (MRI). METHODS: Atherosclerosis model was
      established by feeding high fat diet combined with balloon catheter injury to the
      endothelium in 6 pigs. After 3 months, animals underwent MRI and ILMA
      examination. The ILMA was invasively inserted to the distal part of abdominal
      vein and bilateral common iliac veins. MR sequences including T1 weighted imaging
      (T1WI), T2WI were obtained. MR image data were transferred to post-processing
      station. Luminal border and external elastic membrane of the vessel were
      reconstructed based on the MR images. After co-register these images, vessel
      area, lumen area, vessel wall area and plaque burden in the same lesions imaged
      by different modality were calculated and compared. Finally, all animals were
      scarified and hematoxylin eosin (HE) staining was performed in the targeted
      vessels. Diagnostic accuracy of MR in delineating vessel wall and detecting
      plaque were analyzed and calculated by comparing with pathological results.
      RESULTS: The atherosclerotic model was successfully established in all 6 pigs.
      Good agreement of delineating vessel area, lumen area vessel, wall area and
      plaque burden were found between MRI and pathology with r value of 0.98, 0.95,
      and 0.96, respectively (P < 0.001). Compared with pathological findings, the
      plaque component in corresponding area imaged by MR was as follows: sensitivity
      and specificity of detecting lipid plaque were 77% and 69%, kappa value was 0.75
      +/- 0.19 (P < 0.01); sensitivity and specificity on detecting fibrotic plaque
      were 78% and 73%, Kappa value was 0.78 +/- 0.18 (P < 0.01). The sensitivity and
      specificity of detecting calcified plaque were 100%. ILMA results showed that the
      average lumen area was 49.72 mm(2), average vessel area was 124.08 mm(2), and the
      average vessel wall area was 74.37 mm(2), ILMA slightly overestimated these
      indexes as compared with pathological results. CONCLUSION: The results showed
      that ILMA could be used to image deepened artery and atherosclerotic plaque.
      Detected plaque size, vessel area, lumen area vessel, wall area, and plaque
      burden were comparable to pathological findings. It may thus provide an
      alternative method for detecting atherosclerotic plaque in future research work.

PMID- 24021126
TI  - [Role of the Th17/Treg functional imbalance on the development of atherosclerosis
      in apo E knockout mice].
AB  - OBJECTIVE: To investigate the role of the helper T cells (Th) 17/Treg cell
      imbalance on the development of atherogenesis in apo E knockout mice. METHODS:
      Apo E(-/-) mice were examined at age of 6, 12, 24 and 48 weeks (n = 10 each). Age
      matched C57/B6 mice served as controls. The number of Th17, Treg and dendritic
      cell (DC) was detected by flow cytometry. The levels of interleukin(IL)-6, IL-17A
      and transforming growth factor(TGF)-beta1 were detected by ELISA. The suppression
      ability of Treg was evaluated by mixed lymphocyte reaction. RESULTS: With
      increasing ages, the frequencies of Th17 and Treg in CD4(+) T cells were
      increased (Th17 ratio from 1.00% to 3.14%; Treg ratio from 8.08% to 27.80%) and
      the level of IL-17A was up-regulated [from (87 +/- 15) pg/ml to (191 +/- 26)
      pg/ml], but the rate of Th17/Treg cell and the level of TGF-beta1 remained stable
      during atherogenesis in apo E knockout mice. Furthermore, the phenotype of
      splenic DC was matured and the blood level of IL-6 was up-regulated [from (43 +/-
      5) pg/ml to (104 +/- 11) pg/ml] with aging in apo E(-/-) mice. Addition of IL-6
      to T cells reversed the ability of Treg to suppress the proliferation of
      effective T cells. CONCLUSION: DC overactivation, subsequent increased secretion
      of IL-6, inhibition of Treg cell function and the Th17/Treg cell imbalance play
      key roles on the atherogenesis in apo E(-/-) mice.

PMID- 24021128
TI  - [Epidemiological status and risk factors of hyperuricemia in rural area of the
      Three Gorges].
AB  - OBJECTIVE: To explore the epidemiological status and risk factors of
      hyperuricemia in rural area of the Three Gorges. METHODS: A cross-sectional
      survey was carried out in rural area of Yiling District, Yichang City, which was
      located north-west bank of Xiling Gorge in 2007. A standard structure
      questionnaire was used to collect demographic data, social-economic status and
      life-style features. Fasting venous blood was collected and serum uric acid (SUA)
      was determined. Hyperuricemia was defined as SUA levels >= 417 u mol/L (70 mg/L)
      in men and >= 357 umol/L (60 mg/L) in women. Multiple logistic regression
      analysis was used to analysed the risk factors of hyperuricemia. RESULTS: A total
      of 9354 participants aged 35 and above were included, 19.9% (1866/9354)
      participants were the Three Gorges migrants. Serum uric acid level in men was
      significantly higher than that in women [(285.1 +/- 80.2) umol/L vs. (210.3 +/-
      65.0) umol/L,P < 0.01].Serum uric acid level increased significantly in both
      genders in proportion to increase of age, and was higher in men than in women in
      all age groups (all P < 0.01). The age-adjusted prevalence was significantly
      higher in men than in women (5.6% vs. 3.3%, P < 0.01), and was also higher in men
      aged 35-44 and aged 45-54 than in women (both P < 0.01). There was no
      significance in prevalence of hyperuricemia in both men and women aged 55-64 and
      aged >= 65. After adjusting age, gender, educational level, migration and
      occupation, the multiple logistic regression analysis showed that the prevalence
      of hyperuricemia was higher in alcohol drinking participants than that of non
      alcohol drinking participants (OR = 2.06, 95%CI:1.59-2.67, P < 0.01), and in
      participants used to consume less green vegetables and fruits than in
      participants consuming more green vegetables and fruits (OR = 1.77, 95% CI:1.27
      2.47, P < 0.01). CONCLUSIONS: The prevalence of hyperuricemia is relatively low
      in rural area of the Three Gorges.Alcohol drinking and low intake of green
      vegetables and fruits are the risk factors of hyperuricemia in this population.

PMID- 24021127
TI  - [Population characteristics and impact on heart rate variability, heart rate and
      blood pressure of passive smoking].
AB  - OBJECTIVE: To investigate the basic characteristics of passive smoking
      population, and the impact of passive smoking on heart rate variability, heart
      rate and blood pressure. METHODS: Eighty-six passive smokers [mean age: (52.4 +/-
      7.6) years] were recruited from patients and their relatives who visited
      cardiovascular outpatient department and excluded structural heart disease
      between June 2010 and June 2012, 80 normal subjects who were not exposed to
      smoking served as controls. Questionnaire survey, 24 hours ambulatory
      electrocardiogram examination and blood pressure measurement were performed in
      all recruited subjects. RESULTS: (1) Non-marriage rate [18.60% (16/86) vs. 3.75%
      (3/80), P < 0.01] was significantly higher while education level were
      significantly lower in passive smoking group than in control group. Passive
      smokers were more likely service industry workers [29.07% (25/86) vs. 15.00%
      (12/80), P < 0.05] and had longer daily working time [(7.56 +/- 1.24) h vs. (6.02
      +/- 0.96) h, P < 0.01], and were less likely to be professional technology
      industry employers [20.93% (18/86) vs. 36.25% (29/80), P < 0.05] and managers
      [13.95% (12/86) vs. 38.75% (31/80), P < 0.01] compared to controls. The main
      place of passive smoking was workplace (67.44%, 58/86), entertainment venues
      (63.95%,55/86), restaurants (48.84%, 42/86). (2) Standard of the normal sinus RR
      intervals (SDNN), the normal consecutive sinus RR interval difference between the
      root-mean-square (rMSSD) and adjacent the difference between the RR interval>50
      ms the number of share the percentage (PNN50) were significantly lower in passive
      smoking group than in the control group (all P < 0.05). Every 5 min average of
      the standard deviation of sinus RR cycle (SDNN index) and 24 h every 5 min sinus
      RR interval mean standard deviation (SDANN) were similar between the 2 groups
      (all P > 0.05). Ultra-low-frequency power (VLF), low frequency power (LF), high
      frequency power (HF) and LF/HF were significantly lower in passive smoking group
      than in the control group (all P < 0.01). (3) Heart rate and diastolic blood
      pressure were significantly higher in passive smoking group than in control group
      (all P < 0.05) while systolic blood pressure was similar between the 2 groups (P
      > 0.05). CONCLUSIONS: Marriage status, education level, profession and daily
      working time are independent determinants for passive smoking. Passive smoking
      mainly occurred in the workplace, entertainment venues and restaurants. Passive
      smoking is linked with reduced heart rate variability, increased 24 h average
      heart rate and diastolic blood pressure.

PMID- 24021129
TI  - [A meta-analysis on efficacy of intra-aortic balloon pump therapy in patients
      with acute myocardial infarction].
AB  - OBJECTIVE: To analyze the efficacy and safety of intra-aortic balloon pump (IABP)
      therapy in patients with acute myocardial infarction(AMI) based on the meta
      analysis. METHODS: Eligible published randomized controlled clinical research
      (RCT) were retrieved in the Pubmed, EMBase, Cochrane, China biological medical
      literature, Wanfang, VIP and CNKI database from 1980 to April 2, 2012. The
      analysis was performed with the software of RevMan 5.1. RESULTS: Thirteen RCTs
      with 1958 patients (AMI with IABP therapy, n = 970,without IABP therapy, n = 988)
      were included. The 30-day mortality between the two groups was similar (RR =
      0.77, 95%CI 0.58-1.03, P = 0.08), but the 30-day mortality in the cardiac shock
      subgroup was significantly lower in IABP group than in without IABP group (RR =
      0.65, 95%CI 0.44-0.97, P = 0.04). The 6-month mortality was significantly lower
      in IABP group than in without IABP group (RR = 0.72, 95%CI 0.55-0.94, P = 0.02).
      The incidence of major bleeding was significantly higher in IABP group than in
      without IABP group (RR = 1.43, 95%CI 1.16-1.75, P < 0.01). CONCLUSION: IABP
      therapy is effective to reduce earlier mortality post AMI, particularly for
      patients with cardiac shock.

PMID- 24021131
TI  - [Combination therapy in pulmonary arterial hypertension].

PMID- 24021130
TI  - [Genealogy of mucopolysaccharidosis II].

PMID- 24021132
TI  - The art of doing more with less.

PMID- 24021134
TI  - National neonatal audit reveals high levels of satisfaction in parents.

PMID- 24021137
TI  - Co-ordination glitches affect care of life-limited children.

PMID- 24021139
TI  - Improving healthcare access for difficult-to-reach groups.

PMID- 24021140
TI  - Electronic keypad replaces early warning score paper charts.

PMID- 24021146
TI  - A warning about making generalised conclusions from case studies.
AB  - Discovering children's voices in relation to sexual abuse. 

PMID- 24021148
TI  - Let us strive to avert avoidable deaths.

PMID- 24021149
TI  - Indigenous families' use of a tertiary children's hospital in Australia.
AB  - There has been little research into Australian Indigenous families' use of a
      tertiary paediatric hospital in Western Australia. Scrutiny of existing
      scientific literature and the reports of government and non-governmental
      organisations from 1995 onwards did not identify clear referral pathways, health
      seeking behaviours or preferences of Indigenous families for a culturally safe
      hospital model. Family-centred care requires an understanding of how Indigenous
      children and families arrive at a health service, and the cultural and practical
      implications of large distances and of leaving other family members behind. 

PMID- 24021150
TI  - Once upon a time there was an angry lion: using stories to aid therapeutic care
      with children.
AB  - Storytelling is a useful relationship-building tool to use with children, as
      demonstrated by the work of 'Johnny' and the author, his nurse. Five stages of
      narration - purpose, backstory, pivotal events, evaluation of effects and summary
      - encourage children to recognise and accept feelings such as anger, grief, shame
      and guilt in a safe way and make small steps towards change. It is feasible to
      start engaging children with simple everyday stories, and then go on to develop
      the tale so that the nurse and the child make additions as required. 

PMID- 24021151
TI  - Understanding skin care and skin barrier function in infants.
AB  - Skin care practices involving the application of products to the skin are common.
      This article focuses on these aspects of infant skin care, the importance of skin
      barrier function and how the use of products and therapies applied to the skin
      can affect skin-barrier function. It also challenges current practice and
      tradition, and highlights the evolving body of research into practice and
      tradition. 

PMID- 24021152
TI  - Achieving seniority.

PMID- 24021153
TI  - Fenretinide targets chronic myeloid leukemia stem/progenitor cells by regulation
      of redox signaling.
AB  - AIMS: We have recently shown that fenretinide preferentially targets CD34(+)
      cells of acute myeloid leukemia (AML), and here, we test whether this agent
      exerts the effect on CD34(+) cells of chronic myeloid leukemia (CML), which are
      refractory to imatinib. RESULTS: As tested by colony-forming cell assays using
      clinical specimens, both number and size of total colonies derived from CD34(+)
      CML cells were significantly reduced by fenretinide, and by combining fenretinide
      with imatinib. In particular, colonies derived from erythroid progenitors and
      more primitive pluripotent/multipotent progenitors were highly sensitive to
      fenretinide/fenretinide plus imatinib. Accordantly, fenretinide appeared to
      induce apoptosis in CD34(+) CML cells, particularly with regard to the cells in
      the subpopulation of CD34(+)CD38(-). Through cell quiescent assays, including Ki
      67 negativity test, we added evidence that nonproliferative CD34(+) CML cells
      were largely eliminated by fenretinide. Transcriptome and molecular data further
      showed that mechanisms underlying the apoptosis in CD34(+) CML cells were highly
      complex, involving multiple events of oxidative stress responses. INNOVATION AND
      CONCLUSION: As compared with CD34(+) AML cells, the apoptotic effects of
      fenretinide on CD34(+) CML cells were more prominent whereas less varied among
      the samples of different patients, and also various stress-responsive events
      appeared to be more robust in fenretinide-treated CD34(+) CML cells. Thus, the
      combination of fenretinide with imatinib may represent a more sophisticated
      strategy for CML treatment, in which imatinib mainly targets leukemic blast cells
      through the intrinsic pathway of apopotosis, whereas fenretinide primarily
      targets CML stem/progenitor cells through the oxidative/endoplasmic reticulum
      stress-mediated pathway.

PMID- 24021154
TI  - Multilocus phylogeography of the common lizard Zootoca vivipara at the Ibero
      Pyrenean suture zone reveals lowland barriers and high-elevation introgression.
AB  - BACKGROUND: The geographic distribution of evolutionary lineages and the patterns
      of gene flow upon secondary contact provide insight into the process of
      divergence and speciation. We explore the evolutionary history of the common
      lizard Zootoca vivipara (= Lacerta vivipara) in the Iberian Peninsula and test
      the role of the Pyrenees and the Cantabrian Mountains in restricting gene flow
      and driving lineage isolation and divergence. We also assess patterns of
      introgression among lineages upon secondary contact, and test for the role of
      high-elevation trans-mountain colonisations in explaining spatial patterns of
      genetic diversity. We use mtDNA sequence data and genome-wide AFLP loci to
      reconstruct phylogenetic relationships among lineages, and measure genetic
      structure. RESULTS: The main genetic split in mtDNA corresponds generally to the
      French and Spanish sides of the Pyrenees as previously reported, in contrast to
      genome-wide AFLP data, which show a major division between NW Spain and the rest.
      Both types of markers support the existence of four distinct and geographically
      congruent genetic groups, which are consistent with major topographic barriers.
      Both datasets reveal the presence of three independent contact zones between
      lineages in the Pyrenean region, one in the Basque lowlands, one in the low
      elevation mountains of the western Pyrenees, and one in the French side of the
      central Pyrenees. The latter shows genetic evidence of a recent, high-altitude
      trans-Pyrenean incursion from Spain into France. CONCLUSIONS: The distribution
      and age of major lineages is consistent with a Pleistocene origin and a role for
      both the Pyrenees and the Cantabrian Mountains in driving isolation and
      differentiation of Z. vivipara lineages at large geographic scales. However,
      mountain ranges are not always effective barriers to dispersal, and have not
      prevented a recent high-elevation trans-Pyrenean incursion that has led to
      asymmetrical introgression among divergent lineages. Cytonuclear discordance in
      patterns of genetic structure and introgression at contact zones suggests
      selection may be involved at various scales. Suture zones are important areas for
      the study of lineage formation and speciation, and our results show that
      biogeographic barriers can yield markedly different phylogeographic patterns in
      different vertebrate and invertebrate taxa.

PMID- 24021155
TI  - Profiling microRNA expression in bovine alveolar macrophages using RNA-seq.
AB  - MicroRNAs (miRNAs) are important regulators of gene expression and are known to
      play a key role in regulating both adaptive and innate immunity. Bovine alveolar
      macrophages (BAMs) help maintain lung homeostasis and constitute the front line
      of host defense against several infectious respiratory diseases, such as bovine
      tuberculosis. Little is known, however, about the role miRNAs play in these
      cells. In this study, we used a high-throughput sequencing approach, RNA-seq, to
      determine the expression levels of known and novel miRNAs in unchallenged BAMs
      isolated from lung lavages of eight different healthy Holstein-Friesian male
      calves. Approximately 80 million sequence reads were generated from eight BAM
      miRNA Illumina sequencing libraries, and 80 miRNAs were identified as being
      expressed in BAMs at a threshold of at least 100 reads per million (RPM). The
      expression levels of miRNAs varied over a large dynamic range, with a few miRNAs
      expressed at very high levels (up to 800,000RPM), and the majority lowly
      expressed. Notably, many of the most highly expressed miRNAs in BAMs have known
      roles in regulating immunity in other species (e.g. bta-let-7i, bta-miR-21, bta
      miR-27, bta-miR-99b, bta-miR-146, bta-miR-147, bta-miR-155 and bta-miR-223). The
      most highly expressed miRNA in BAMs was miR-21, which has been shown to regulate
      the expression of antimicrobial peptides in Mycobacterium leprae-infected human
      monocytes. Furthermore, the predicted target genes of BAM-expressed miRNAs were
      found to be statistically enriched for roles in innate immunity. In addition to
      profiling the expression of known miRNAs, the RNA-seq data was also analysed to
      identify potentially novel bovine miRNAs. One putatively novel bovine miRNA was
      identified. To the best of our knowledge, this is the first RNA-seq study to
      profile miRNA expression in BAMs and provides an important reference dataset for
      investigating the regulatory roles miRNAs play in this important immune cell
      type. 

PMID- 24021156
TI  - Impact of negative affectively charged stimuli and response style on cognitive
      control-related neural activation: an ERP study.
AB  - The canonical AX-CPT task measures two forms of cognitive control: sustained goal
      oriented control ("proactive" control) and transient changes in cognitive control
      following unexpected events ("reactive" control). We modified this task by adding
      negative and neutral International Affective Picture System (IAPS) pictures to
      assess the effects of negative emotion on these two forms of cognitive control.
      Proactive and reactive control styles were assessed based on measures of behavior
      and electrophysiology, including the N2 event-related potential component and
      source space activation (Low Resolution Tomography [LORETA]). We found slower
      reaction-times and greater DLPFC activation for negative relative to neutral
      stimuli. Additionally, we found that a proactive style of responding was related
      to less prefrontal activation (interpreted to reflect increased efficiency of
      processing) during actively maintained previously cued information and that a
      reactive style of responding was related to less prefrontal activation
      (interpreted to reflect increased efficiency of processing) during just-in-time
      environmentally triggered information. This pattern of results was evident in
      relatively neutral contexts, but in the face of negative emotion, these
      associations were not found, suggesting potential response style-by-emotion
      interaction effects on prefrontal neural activation. 

PMID- 24021157
TI  - Mechanism of arctigenin-mediated specific cytotoxicity against human lung
      adenocarcinoma cell lines.
AB  - The lignan arctigenin (ARG) from the herb Arctium lappa L. possesses anti-cancer
      activity, however the mechanism of action of ARG has been found to vary among
      tissues and types of cancer cells. The current study aims to gain insight into
      the ARG mediated mechanism of action involved in inhibiting proliferation and
      inducing apoptosis in lung adenocarcinoma cells. This study also delineates the
      cancer cell specificity of ARG by comparison with its effects on various normal
      cell lines. ARG selectively arrested the proliferation of cancer cells at the
      G0/G1 phase through the down-regulation of NPAT protein expression. This down
      regulation occurred via the suppression of either cyclin E/CDK2 or cyclin H/CDK7,
      while apoptosis was induced through the modulation of the Akt-1-related signaling
      pathway. Furthermore, a GSH synthase inhibitor specifically enhanced the
      cytotoxicity of ARG against cancer cells, suggesting that the intracellular GSH
      content was another factor influencing the susceptibility of cancer cells to ARG.
      These findings suggest that specific cytotoxicity of ARG against lung cancer
      cells was explained by its selective modulation of the expression of NPAT, which
      is involved in histone biosynthesis. The cytotoxicity of ARG appeared to be
      dependent on the intracellular GSH level. 

PMID- 24021158
TI  - Clinical and radiologic results of arthroscopic biceps tenodesis with suture
      anchor in the setting of rotator cuff tear.
AB  - BACKGROUND: The purpose of this study was to report clinical and radiologic
      results of arthroscopic biceps tenodesis with 1 suture anchor in rotator cuff
      tear patients. METHODS: During a 2-year period, 84 consecutive patients (45 men;
      39 women) who underwent arthroscopic tenodesis were evaluated retrospectively.
      Mean age was 58 years. The primary indication for surgery was rotator cuff tear
      in 96.4%. Tenodesis was performed with 1 suture anchor placed in the bicipital
      groove with 2 knots, 1 lasso-type and 1 that pierced the tendon. At final follow
      up at a mean of 33.2 months, visual analog scale pain (pain-VAS) score, shoulder
      scores (American Shoulder and Elbow Surgeons [ASES] and Constant score), Popeye
      deformity (PD), anterior arm pain, and elbow flexion power were evaluated.
      Postoperative magnetic resonance images were evaluated in 60 patients to
      determine the integrity of the tenodesis and the location of the suture anchor.
      RESULTS: The average pain-VAS decreased from 5.3 to 1.4 (P < .001). ASES and
      Constant scores significantly increased, from 42.9 and 56.2 to 85.2 and 82.5,
      respectively. PD occurred in 11 patients (12.9%), and 2 (2.3%) had self
      consciousness; however, no patients complained about the deformity and the PD did
      not correlate with poorer clinical scores. Six patients (7.1%) complained of
      anterior cramping pain. Elbow flexion power was similar compared with the
      contralateral side. In postoperative magnetic resonance imagine analysis, 15
      patients (25%) showed distal migration of tenodesed biceps tendon, although only
      6 (7.1%) had clinical PD. Postoperative clinical outcomes were not influenced by
      the location of the suture anchor within the bicipital groove. CONCLUSIONS:
      Arthroscopic biceps tenodesis with 1 suture anchor resulted in good clinical
      outcomes at 2 years postoperatively. PD was seen in 12.9% of the patients.

PMID- 24021159
TI  - Complications rates, reoperation rates, and the learning curve in reverse
      shoulder arthroplasty.
AB  - BACKGROUND: Reverse shoulder arthroplasty (RSA) has ushered a new era in shoulder
      surgery. However, the results of RSA also described the complication rates
      associated with the procedure as inordinate and a learning curve associated with
      the incidence of complications. METHODS: The records of 112 patients who
      underwent 114 RSA procedures by the senior author (G.I.G.) were reviewed for
      complications related to a RSA. Of these, 93 RSA procedures were the primary
      treatment for the shoulder, and 21 were revisions. RESULTS: The total
      complication rate for the entire group was 7%. Complications included 3
      periprosthetic fractures, 3 hematomas, 1 acromion fracture, and 1 deep infection.
      The complication rate was 19% in the revision RSA group and 4.3% in the primary
      RSA group (P <= .02). Complication rates in the initial RSA patients in this
      series did not differ from the final procedures in this series (P = .96). The
      total reoperation rate was 5.3%, and was 19% in the revision RSA group vs 2.2% in
      the primary RSA group (P <= .02). CONCLUSION: Complications and reoperations
      associated with a RSA, although significant, occurred at much lower rate than in
      previous reports. This series demonstrates a significant difference in
      complication rates and reoperation rates between primary and revision RSA.
      Revision RSA complications and reoperations were far more common than in primary
      RSA procedures. No evidence of a learning curve related to surgical experience
      was demonstrated in this series.

PMID- 24021160
TI  - Bioisosteric replacement and related analogs in the design, synthesis and
      evaluation of ligands for muscarinic acetylcholine receptors.
AB  - Previous structure-activity relationship studies involving a series of lactone
      based muscarinic ligands identified a lead compound containing a
      diphenylmethylpiperazine moiety (4; IC50 = 340 nM). The purpose of the present
      work is to investigate 1,3-benzodioxoles, 4,4-diethyl substituted
      tetrahydrofurans, 5-substituted oxazolidinones and chromones as bioisosteric
      replacements for the lactone ring in a novel series of muscarinic ligands. The
      approach provided compounds with improved % inhibition values and identified a
      non-selective muscarinic ligand with an IC50 value of 280 nM. The structure
      activity relationship for this new series will be discussed. Selected compounds
      were evaluated in preliminary assays for subtype selectivity and were found to be
      non-selective. 

PMID- 24021161
TI  - Dante's description of narcolepsy.
AB  - Sleep, sleepiness, and dreaming are expressed throughout Dante Alighieri's (1265
      1321) the Divine Comedy from the start of his journey through the afterlife. In
      the book, Dante complains that he is "full of sleep," and he experiences sudden
      wake-dreaming transitions, short and refreshing naps, visions and hallucinations,
      unconscious behaviors, episodes of muscle weakness, and falls which are always
      triggered by strong emotions. Taken together these signs are highly reminiscent
      of narcolepsy, a term coined in 1880 by Gelineau to define a disease consisting
      of daytime irresistible sleep episodes with remarkable dream mentation, sleep
      paralysis, hallucinations, and cataplexy (falls triggered by strong emotions).
      Sleep, sleepiness, and episodes of sudden weakness triggered by emotions are
      Dante's literary fingerprints from his earliest works, pointing to a lifelong
      autobiographic trait. In the 19th century, Cesare Lombroso speculated that Dante
      had epilepsy, as he had suffered from frequent spells and hallucinations.
      However, the multiple emotionally triggered falls Dante experienced in the Divine
      Comedy contrast with the epileptic seizure he depicted in one of the damned
      individuals. It is possible that Dante may have intuitively grasped the main
      features of narcolepsy, but it also is plausible that Dante's sleep, dreams,
      hallucinations, and falls are clues to a lifelong pathologic trait and that Dante
      may have known of or had narcolepsy. 

PMID- 24021162
TI  - Malaria indicator surveys demonstrate a markedly lower prevalence of malaria in
      large cities of sub-Saharan Africa.
AB  - BACKGROUND: One in eight sub-Saharan Africans now lives in a city with a
      population greater than 750,000. Decision makers require additional evidence
      regarding the burden of malaria in these large cities. This paper presents
      results from analysis of existing data from nationwide household surveys
      measuring malaria parasitaemia by microscopy among children six to 59 months of
      age in 15 countries of sub-Saharan Africa. METHODS: Geo-coordinates for each
      survey cluster were used to determine the distance from the cluster to the centre
      of each of 16 large cities with populations greater than 750,000. Geo-coordinates
      of each site within 25 km of the centre were entered into Google Earth to obtain
      a satellite image of the location and determine whether it was within the
      boundaries of the metropolis. In the case of two countries for which survey geo
      coordinates were not available, clusters located in an additional four large
      cities were identified based upon their designated district. Data from all sites
      within city boundaries were pooled together and compared to data from all rural
      sites within 150 km of the city centre or in the same zone of malaria endemicity.
      RESULTS: Of the 20 large cities, only in Ouagadougou were more than 10% of
      children found to have a malaria infection. The prevalence was less than 5% for
      16 of these cities. Apart from Antananarivo where both the large city and the
      comparison rural communities were parasite-free, the prevalence in each of the
      large cities was 0 to 40% of that found among children living in rural
      communities within 150 km of these cities or within the same zone of malaria
      endemicity. In 14 of the 20 large cities, all of the children living in 75% or
      more of the clusters were malaria parasite-free. CONCLUSIONS: Existing data from
      malaria indicator surveys can be used to document the substantially lower
      prevalence of malaria in specific large cities. These findings will help policy
      makers, public health programmers and clinical workers in each country to develop
      and promote malaria control strategies that are suited to large cities as well as
      to those living in smaller communities.

PMID- 24021163
TI  - POME is treated for removal of color from biologically treated POME in fixed bed
      column: applying wavelet neural network (WNN).
AB  - As Malaysia is one of the world's largest producer of palm oil, large amounts of
      palm oil mill effluent (POME) is generated. It was found that negatively charged
      components are accountable for POME color. An attempt was made to remove residual
      contaminants after conventional treatment using anion base resin. Adsorption
      experiments were carried out in fixed bed column. Various models such as the
      Thomas, the Yoon-Nelson, the Wolborska and BDST model were used to fit the
      experimental data. It was found that only the BDST model was fitted well at the
      initial breakthrough time. A wavelet neural network model (WNN) was developed to
      model the breakthrough curves in fixed bed column for multicomponent system. The
      results showed that the WNN model described breakthrough curves better than the
      commonly used models. The effects of pH, flow rate and bed depth on column
      performance were investigated. It was found that the highest uptake capacity was
      obtained at pH 3. The exhaustion time appeared to increase with increase in bed
      length and decrease in flow rate. 

PMID- 24021164
TI  - Preparation of stir cake sorptive extraction based on poly(4-vinylbenzoic acid
      divinylbenzene) monolith and its application in sensitive determination of beta
      agonists in milk and swine urine samples.
AB  - In this study, a new stir cake sorptive extraction (SCSE) based on poly(4
      vinylbenzoic acid-divinylbenzene) (VBADB) monolith was prepared. The effect of
      preparation conditions of monolith on extraction efficiencies was investigated in
      detail. Several characteristic techniques, such as elemental analysis, infrared
      spectroscopy, mercury intrusion porosimetry and scanning electron microscopy were
      used to characterize the monolithic material. The combination of SCSE-VBADB with
      high-performance liquid chromatography tandem mass spectrometry (HPLC/MS/MS)
      detection was developed for sensitive determination of ultra-trace beta-agonists
      in milk and swine urine samples. In order to obtain the optimal extraction
      conditions of SCSE-VBADB for beta-agonists, several extractive parameters,
      including pH values and ionic strength in sample matrix, extraction and
      desorption time were optimized. Under the optimum conditions, the limits of
      detection (S/N=3) for the target analytes were 0.007-0.030 MUg/L in milk and
      0.002-0.011 MUg/L in swine urine, respectively. Excellent method reproducibility
      was achieved in terms of intraday and interday precisions, indicated by the RSDs
      of both <10.0%, respectively. Finally, the proposed method was successfully used
      to detect beta-agonists in different milk and swine urines samples. Acceptable
      recoveries ranged from 50.3% to 113% and 50.1% to 92.2% for milk and swine urine
      samples, respectively; and the RSDs for reproducibility were less than 8.0% for
      target analytes in all real samples.

PMID- 24021165
TI  - Sea-urchin-like iron oxide nanostructures for water treatment.
AB  - To obtain adsorbents with high capacities for removing heavy metals and organic
      pollutants capable of quick magnetic separation, we fabricated unique sea-urchin
      like magnetic iron oxide (mixed gamma-Fe2O3/Fe3O4 phase) nanostructures (called u
      MFN) with large surface areas (94.1m(2) g(-1)) and strong magnetic properties
      (57.9 emu g(-1)) using a simple growth process and investigated their potential
      applications in water treatment. The u-MFN had excellent removal capabilities for
      the heavy metals As(V) (39.6 mg g(-1)) and Cr(VI) (35.0 mg g(-1)) and the organic
      pollutant Congo red (109.2 mg g(-1)). The u-MFN also displays excellent
      adsorption of Congo red after recycling. Because of its high adsorption capacity,
      fast adsorption rate, and quick magnetic separation from treated water, the u-MFN
      developed in the present study is expected to be an efficient magnetic adsorbent
      for heavy metals and organic pollutants in aqueous solutions.

PMID- 24021166
TI  - Ecotoxicological assessment of a high energetic and insensitive munitions
      compound: 2,4-dinitroanisole (DNAN).
AB  - The high explosive nitroaromatic 2,4-dinitroanisole (DNAN) is less shock
      sensitive than 2,4,6-trinitrotoluene (TNT), and is proposed as a TNT replacement
      for melt-cast formulations. Before using DNAN in munitions and potentially
      leading to environmental impact, the present study examines the ecotoxicity of
      DNAN using selected organisms. In water, DNAN decreased green algae
      Pseudokirchneriella subcapitata growth (EC50 = 4.0mg/L), and bacteria Vibrio
      fischeri bioluminescence (Microtox, EC50 = 60.3mg/L). In soil, DNAN decreased
      perennial ryegrass Lolium perenne growth (EC50 =7 mg/kg), and is lethal to
      earthworms Eisenia andrei (LC50 = 47 mg/kg). At sub-lethal concentrations, DNAN
      caused an avoidance response (EC50 = 31 mg/kg) by earthworms. The presence of
      DNAN and 2-amino-4-nitroanisole in earthworms and plants suggested a role of
      these compounds in DNAN toxicity. Toxicity of DNAN was compared to TNT, tested
      under the same experimental conditions. These analyses showed that DNAN was
      equally, or even less deleterious to organism health than TNT, depending on the
      species and toxicity test. The present studies provide baseline toxicity data to
      increase the understanding of the environmental impact of DNAN, and assist
      science-based decision makers for improved management of potential DNAN
      contaminated sites.

PMID- 24021168
TI  - Genotoxicity evaluation of individual cigarette smoke toxicants using the in
      vitro gammaH2AX assay by high content screening.
AB  - Cigarette smoke is a complex mixture consisting of more than 5600 identified
      chemical constituents of which approximately 150 have been identified so far as
      "tobacco smoke toxicants". Proposals made by the World Health Organisation
      Framework Convention on Tobacco Control mandate the lowering of nine tobacco
      smoke priority toxicants, including 4-(methylnitrosamino)-1-(3-pyridyl)-1
      butanone (NNK), N-nitrosonornicotine (NNN), and benzo[a]pyrene (B[a]P) and
      monitoring the levels of a further nine including cadmium. Here, we evaluated the
      genotoxic potential in human bronchial epithelial BEAS-2B cells of four cigarette
      smoke toxicants; NNK, NNN, B[a]P and cadmium using the novel in vitro gammaH2AX
      assay by High Content Screening (HCS). We also examined the genotoxicity of
      binary mixtures of NNK and NNN reporting their relative contribution to the
      genotoxic end-point. The results of this preliminary assessment showed that the
      in vitro gammaH2AX assay by HCS could be used as a pre-screening tool to detect
      and quantify the genotoxicity effect of cigarette smoke toxicants individually
      and in binary mixture. Moreover, the data produced could contribute to the
      prioritisation of toxicant reduction research in modified tobacco products. 

PMID- 24021167
TI  - Fibromyalgia and coeliac disease: a media hype or an emerging clinical problem?
AB  - OBJECTIVES: Fibromyalgia (FM) association with autoimmune diseases has been
      widely reported in literature. Coeliac disease (CD) is a small intestine immune
      mediated disorder triggered by gluten ingestion in genetically predisposed
      patients. In recent years, the Internet and the non-medical press have reported a
      correlation between gluten-related disorders and fibromyalgia-like symptoms. The
      aim of our study was to verify a possible association between FM and CD, by
      assessing the prevalence of CD in a cohort of FM patients and vice versa.
      METHODS: 90 consecutive subjects from our Rheumatologic outpatient clinic who had
      been diagnosed with FM were serologically tested for CD and positive patients
      underwent esophagogastroduodenoscopy to obtain duodenal biopsies. A second group
      of 114 consecutive subjects from our Coeliac Disease outpatient clinic were
      investigated for the presence of FM-like symptoms through a questionnaire.
      Patients reporting chronic widespread pain were addressed to a rheumatologist for
      further evaluation. RESULTS: The overall prevalence of CD in our FM patients was
      identical to that expected in general population (around 1%). In our CD group 17
      patients (14.9%) reported chronic widespread pain at the questionnaire and 13
      (11.4%) satisfied ACR 1990 criteria for FM. Their symptoms had not been modified
      by GFD. CONCLUSIONS: A serological screening for CD is not recommended in FM
      patients but rather a case-finding strategy should be performed. At the same
      time, proposals of GFD in FM patients, in absence of a well-established diagnosis
      of CD, should be rigorously avoided.

PMID- 24021169
TI  - The critical importance of defined media conditions in Daphnia magna nanotoxicity
      studies.
AB  - Due to the widespread use of silver nanoparticles (AgNPs), the likelihood of them
      entering the environment has increased and they are known to be potentially
      toxic. Currently, there is little information on the dynamic changes of AgNPs in
      ecotoxicity exposure media and how this may affect toxicity. Here, the colloidal
      stability of three different sizes of citrate-stabilized AgNPs was assessed in
      standard strength OECD ISO exposure media, and in 2-fold (media2) and 10-fold
      (media10) dilutions by transmission electron microscopy (TEM) and atomic force
      microscopy (AFM) and these characteristics were related to their toxicity towards
      Daphnia magna. Aggregation in undiluted media (media1) was rapid, and after
      diluting the medium by a factor of 2 or 10, aggregation was reduced, with minimal
      aggregation over 24h occurring in media10. Acute toxicity measurements were
      performed using 7nm diameter particles in media1 and media10. In media10 the EC50
      of the 7nm particles for D. magna neonates was calculated to be 7.46MUgL(-1) with
      upper and lower 95% confidence intervals of 6.84MUgL(-1) and 8.13MUgL(-1)
      respectively. For media1, an EC50 could not be calculated, the lowest observed
      adverse effect concentration (LOAEC) of 11.25MUgL(-1) indicating a significant
      reduction in toxicity compared to that in media10. The data suggest the increased
      dispersion of nanoparticles leads to enhanced toxicity, emphasising the
      importance of appropriate media composition to fully assess nanoparticle toxicity
      in aquatic ecotoxicity tests. 

PMID- 24021171
TI  - Cone visual pigments.
AB  - Cone visual pigments are visual opsins that are present in vertebrate cone
      photoreceptor cells and act as photoreceptor molecules responsible for photopic
      vision. Like the rod visual pigment rhodopsin, which is responsible for scotopic
      vision, cone visual pigments contain the chromophore 11-cis-retinal, which
      undergoes cis-trans isomerization resulting in the induction of conformational
      changes of the protein moiety to form a G protein-activating state. There are
      multiple types of cone visual pigments with different absorption maxima, which
      are the molecular basis of color discrimination in animals. Cone visual pigments
      form a phylogenetic sister group with non-visual opsin groups such as pinopsin,
      VA opsin, parapinopsin and parietopsin groups. Cone visual pigments diverged into
      four groups with different absorption maxima, and the rhodopsin group diverged
      from one of the four groups of cone visual pigments. The photochemical behavior
      of cone visual pigments is similar to that of pinopsin but considerably different
      from those of other non-visual opsins. G protein activation efficiency of cone
      visual pigments is also comparable to that of pinopsin but higher than that of
      the other non-visual opsins. Recent measurements with sufficient time-resolution
      demonstrated that G protein activation efficiency of cone visual pigments is
      lower than that of rhodopsin, which is one of the molecular bases for the lower
      amplification of cones compared to rods. In this review, the uniqueness of cone
      visual pigments is shown by comparison of their molecular properties with those
      of non-visual opsins and rhodopsin. This article is part of a Special Issue
      entitled: Retinal Proteins - You can teach an old dog new tricks. 

PMID- 24021170
TI  - Differences in butadiene adduct formation between rats and mice not due to
      selective inhibition of CYP2E1 by butadiene metabolites.
AB  - CYP2E1 metabolizes 1,3-butadiene (BD) into genotoxic and possibly carcinogenic
      1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane (DEB), and 1,2-epoxy-3,4
      butanediol (EB-diol). The dose response of DNA and protein adducts derived from
      BD metabolites increases linearly at low BD exposures and then saturates at
      higher exposures in rats, but not mice. It was hypothesized that differences in
      adduct formation between rodents reflect more efficient BD oxidation in mice than
      rats. Herein, we assessed whether BD-derived metabolites selectively inhibit rat
      but not mouse CYP2E1 activity using B6C3F1 mouse and Fisher 344 rat liver
      microsomes. Basal CYP2E1 activities toward 4-nitrophenol were similar between
      rodents. Through IC50 studies, EB was the strongest inhibitor (IC50 54MUM, mouse;
      98MUM, rat), BD-diol considerably weaker (IC50 1200MUM, mouse; 1000MUM, rat), and
      DEB inhibition nonexistent (IC50>25mM). Kinetic studies showed that in both
      species EB and BD-diol inhibited 4-nitrophenol oxidation through two-site
      mechanisms in which inhibition constants reflected trends observed in IC50
      studies. None of the reactive epoxide metabolites inactivated CYP2E1
      irreversibly. Thus, there was no selective inhibition or inactivation of rat
      CYP2E1 by BD metabolites relative to mouse Cyp2e1, and it can be inferred that
      CYP2E1 activity toward BD between rodent species would similarly not be impacted
      by the presence of BD metabolites. Inhibition of CYP2E1 by BD metabolites is then
      not responsible for the reported species difference in BD metabolism, formation
      of BD-derived DNA and protein adducts, mutagenicity and tumorigenesis. 

PMID- 24021172
TI  - The new era for the treatment of psoriasis and psoriatic arthritis: perspectives
      and validated strategies.
AB  - Psoriatic Arthritis (PsA) is a chronic inflammatory arthropathy associated with
      psoriasis. Psoriasis (PsO) is a chronic, inflammatory skin disease, characterized
      by hyperproliferation and aberrant differentiation of keratinocytes. PsA and PsO
      can be considered as a unique disease and are immune-mediated diseases and both
      innate and adaptive immunity play a role in their pathogenesis. Initially, PsO
      and PsA were thought to be Th1-mediated diseases, however, in the last years,
      several studies have shown the role of interleukin 17 (IL-17) and Th17 cells in
      the pathogenesis of PsA and PsO. Th17 cells have been detected in dermal
      infiltrates of psoriatic lesions as well as in synovial fluid. Interleukin (IL)
      23, produced by antigen presenting cells (APC), especially by dendritic cells
      (DC), is the key regulator cytokine for Th17 and IL-17 production. In this review
      we discuss the role of IL-17 and IL-23 in the pathogenesis of PsO and PsA and
      their role as therapeutic targets for PsO and PsA treatment. 

PMID- 24021173
TI  - Flexural and compressive mechanical behaviors of the porous titanium materials
      with entangled wire structure at different sintering conditions for load-bearing
      biomedical applications.
AB  - The entangled titanium materials with various porosities have been investigated
      in terms of the flexural and compressive mechanical properties and the
      deformation and failure modes. The effect of the sintering parameters on the
      mechanical properties and the porosity reduction has been comprehensively
      studied. The results indicate that both the flexural and compressive mechanical
      properties increase significantly as the porosity decreases. In the porosity
      range investigated the flexural elastic modulus is in the range of 0.05-6.33GPa,
      the flexural strength is in the range of 9.8-324.9MPa, the compressive elastic
      modulus is in the range of 0.03-2.25GPa, and the compressive plateau stress is in
      the range of 2.3-147.8MPa. The mechanical properties of the entangled titanium
      materials can be significantly improved by sintering, which increase remarkably
      as the sintering temperature and/or the sintering time increases. But on other
      hand, the sintering process can induce the porosity reduction due to the
      oxidation on the titanium wire surface. 

PMID- 24021175
TI  - [Surgical options and application principles of combined cataract and glaucoma
      surgery].
AB  - The trend of the coincident cataract and glaucoma is likely to increase worldwide
      and it is a common finding in the aging population. The management of combined
      presence of cataract and glaucoma is a common clinical challenge. Due to the
      development of new microscopy and cataract phacoemulsification techniques, we
      have more choices of surgical method. And the best surgical strategy will depend
      on the clinicians' surgical techniques and patients' characteristics. 

PMID- 24021174
TI  - The mechanics of hyaluronic acid/adipic acid dihydrazide hydrogel: towards
      developing a vessel for delivery of preadipocytes to native tissues.
AB  - Promising treatment approaches in repairing tissue defects include implementation
      of regenerative medicine strategies, particularly delivery of preadipocytes to
      sites where adipose tissue damage needs to be repaired or where fat needs to be
      generated. In this study, we suggest that the injectable hyaluronic acid/adipic
      acid dihydrazide (HA/ADH) hydrogel may be an adipose-tissue-like material in
      terms of biological compatibility as well as mechanical behavior. First, we show
      that the hydrogel enables and supports growth, proliferation and differentiation
      of 3T3-L1 preadipocytes. Second, given that adipose tissue is a weight-bearing
      biological structure, we investigate the large deformation mechanical behavior of
      the hydrogel with and without embedded preadipocytes, by performing confined and
      unconfined compression tests and then calibrating a strain energy density (SED)
      function to the results. Four test groups were examined: (1) Hydrogel specimens
      right after the preparation without cells, (2) and (3) 3-days-cultured hydrogel
      specimens with and without cells, respectively, and (4) 6-days-cultured hydrogel
      specimens with cells. A one-term Ogden SED was found to adequately describe the
      hyperelastic behavior of the hydrogel specimens in all experimental groups.
      Importantly, we found that the mechanical properties of the hydrogel, when
      subjected to compression, are in good agreement with those of native adipose
      tissue, with the better fit occurring 3-6 days after preparation of the hydrogel.
      Third, computational finite element studies of the mechanical (stress-strain)
      behavior of the HA/ADH hydrogel when containing mature adipocytes indicated that
      the stiffnesses of the constructs were mildly affected by the presence of the
      adipocytes. Hence, we conclude that injectable HA/ADH hydrogel may serve as a
      vessel for protecting preadipocytes during, and at a short-term after delivery to
      native tissues, e.g. in research towards regenerative medicine in tissue
      reconstructions. 

PMID- 24021176
TI  - [Debate on the advantages and disadvantages of multifocal and monofocal
      intraocular lens].
AB  - Phacoemulsification and intraocular lens implantation is the most effective
      treatment of cataract.Traditional intraocular lens were mainly monofocal.
      Postoperative patients can return to a certain distance vision or near vision,
      but because of the loss of accommodative power, patients must rely on glasses to
      complete the work of the different distances, the postoperative life there is
      still a lot of inconvenience. In recent years, the design of multifocal
      intraocular lens has been the focus of basic and applied research in cataract,
      but so far the researchers still could not have agreement with the strengths and
      weaknesses of the multifocal and monofocal intraocular lens. There are three
      major controversies: First of all, whether it is worth the expense of contrast
      sensitivity and increased visual disturbance in return for compensatory
      adjustment? Second, whether it is possible to really get the full range of vision
      and to get rid of dependence on glasses to use multifocal intraocular lens?
      Third, how to grasp the indications of multifocal intraocular lens to play to
      their strengths. 

PMID- 24021177
TI  - [Several problems of clinical application of Toric IOL].
AB  - Nowadays, ultrasonic emulsification combined intraocular lens (IOL) implantation
      has been the mainstream technology for treating a cataract. In order to further
      improve the patients' visual quality after surgery, Toric IOL has been used in
      clinic. Toric IOL can correct corneal astigmatism stably, reasonably and
      predictably. Clinicians should pay more attention to the details and according to
      the patients' conditions to make personalized options when choosing Toric IOL. 

PMID- 24021178
TI  - [Long-term outcome after bilateral cataract surgery in infants with congenital
      cataract].
AB  - OBJECTIVE: To evaluate the long-term visual outcome and complications after
      bilateral congenital cataract surgery performed prior to 12 months of age.
      METHODS: A prospective case study. 31 cases (62 eyes) of bilateral congenital
      cataract were included.All patients received bilateral cataract extraction
      combined with primary capsulotomy and anterior vitrectomy simultaneously.After
      the operation, all patients wore aphakic glasses during the follow-up period.The
      unilateral and bilateral visual acuities (VA) at the last visit were determined
      and post-operative complications were evaluated, and the relationship between
      bilateral VA and the length of the follow-up period was also analyzed. RESULTS:
      The median age at surgery was 3.0 M (0.5 to 11 M) , the median follow-up period
      was 4.0 years (3.0 to 8.5 years). 37 out of 62 eyes (59.68%) achieved unilateral
      best corrected visual acuity equal or better than 0.3. 27 among 31 cases (87.1%)
      achieved binocular best corrected visual acuity equal or better than
      0.3.Binocular best corrected visual acuity improved with the increase in the
      follow-up period and the patients' age (R(2) = 0.135,P = 0.0024) .Post-operative
      complications included strabismus (7 cases, 22.58%), nystagmus (13 cases,
      41.94%), optical opacity (3 cases, 9.68%), ocular hypertension (1 cases, 3.23%).
      CONCLUSIONS: Surgery for congenital cataracts performed prior to 12 months of age
      is safe, and most of the subjects can achieve functional vision acuity. As these
      children age, the bilateral best corrected visual acuity can still keep
      improving.

PMID- 24021179
TI  - [Early visual results and mechanism of pseudo-accommodation of the Quatrix
      aspheric intraocular lens].
AB  - OBJECTIVE: To assess the clinical and visual outcomes of the implantation of the
      Quatrix intraocular lens (IOL) and investigate the mechanism of pseudo
      accommodation of these lens. METHODS: Patients (67 eyes )received cataract
      surgery were offered the Quatrix IOL (32 eyes) and AR40e IOL (35 eyes). The
      patients' refractive status, uncorrected and best corrected distance visual
      acuities were assessed preoperatively, 1 week, 1 month and 3 months after
      surgery. Using the Ray-tracing method, the root mean square (RMS) values of the
      higher order aberrations for each subject with pupil diameters of 4.0 mm under
      accommodative stimuli were calculated. RESULT: The mean uncorrected distance
      visual acuity improved significantly from 0.70 to 0.22 logMAR by the end of 3
      months postoperative for the Quatrix group. The mean uncorrected near acuity was
      statistically significantly higher in the Quatrix group than in the AR40e group
      at the 6 months post-operative examination. The internal spherical aberration
      increased and changed from a positive to a negative value with increasing
      accommodation at 4.0 mm of pupil diameter under accommodative stimuli for the
      Quatrix group. The total and internal high order aberrations had no significant
      difference after surgery in the control group. CONCLUSION: Results show that the
      Quatix IOL is safe, effective, and stable. It provided some degree of pseudo
      accommodation. Flexure changes to the optics of the Quatrix IOL during
      accommodation could explain some of the pseudo-accommodation of this IOL.

PMID- 24021180
TI  - [Changes of dynamic visual acuity after phacoemulsification combined with
      intraocular lens implantation].
AB  - OBJECTIVE: To compare the spatial resolutions of dynamic optotypes at different
      speed levels among age-related cataract patients, older people with clear
      crystalline lenses and senile individuals implanted with intraocular lenses
      (IOL). METHODS: The control study recruited 24 patients (48 eyes) with age
      related cataract scheduled for phacoemulsification surgery in our hospital
      between Jul. 2011 and Dec. 2011 in the cataract group. Twenty-three older
      volunteers (46 eyes) with clear crystalline lenses were enrolled in the normal
      group. The postoperative group consisted of 23 contemporary cases implanted with
      spherical monofocal non-yellow-tinted IOL and followed up for 3 months
      postoperatively, of which 5 cases undertook unilateral surgery for normal visual
      acuity of the contralateral eye. Monocular and binocular best corrected visual
      acuity at static condition and binocular spatial resolution of optotypes at
      speeds of 15, 30, 60 and 90 degrees per second (dps) were measured by a
      logarithmic visual acuity chart. Statistical analysis was performed with
      student's t test (with Bonferroni correction). RESULTS: Binocular spatial
      resolutions at speeds of 15, 30, 60 and 90 dps were (0.29 +/- 0.16), (0.34 +/-
      0.17), (0.47 +/- 0.19) and (0.52 +/- 0.17), respectively, in the cataract group,
      and (0.04 +/- 0.06), (0.06 +/- 0.06), (0.12 +/- 0.09) and (0.15 +/- 0.11),
      respectively, in the normal group. Resolution of dynamic optotypes at the four
      speed levels were statistically lower in the cataract group than in the normal
      group (t = -6.952, -7.558, -8.235, -8.737; P < 0.01). Velocity dependent spatial
      resolution changes manifested statistically higher values in the cataract group
      than in the normal group, with (0.14 +/- 0.13) versus (0.03 +/- 0.05) at the
      interval between static and 15 dps (t0-15 dps = -3.874, P = 0.001) and (0.13 +/-
      0.09) versus (0.06 +/- 0.07) at the interval between 30 dps and 60 dps (t30-60
      dps = -3.113, P = 0.003). In the postoperative group, resolutions of dynamic
      optotypes at speeds of 15, 30, 60 and 90 dps were (0.03 +/- 0.05), (0.05 +/-
      0.07), (0.11 +/- 0.10) and (0.16 +/- 0.11), respectively. Dynamic visual acuities
      at all the four speed levels were statistically higher in the postoperative group
      than in the cataract group (t = -7.336, -7.673, -8.328, -8.583; P < 0.01) and
      compatible to that in the normal group (t = 0.669, 0.400, 0.372, -0.504; P >
      0.05). Visual acuity differences between consecutive speed levels were comparable
      between the postoperative group and the normal group (t = 0.586, -0.326, 0.133, 
      1.600; P > 0.05), while at the interval between static and 15 dps and the
      interval between 30 dps and 60 dps, the postoperative group exhibited lower
      visual acuity changes than the cataract group, with (0.03 +/- 0.04) versus (0.14
      +/- 0.13) (t0-15 dps = -4.182, P < 0.01) and (0.05 +/- 0.06) versus (0.13 +/-
      0.09) (t30-60 dps = -3.334, P = 0.002), respectively. CONCLUSIONS: As the
      optotype's moving speed increased, spatial resolutions declined more rapidly in
      patients with age-related cataract. Phacoemulsification combined with IOL
      implantation could effectively restore the spatial resolution of dynamic
      optotypes.

PMID- 24021181
TI  - [The protective effect of photochromic intraocular lens on visible light-induced
      lesion in cultured retinal pigment epithelium].
AB  - OBJECTIVE: To evaluate the protective effect of photochromic intraocular lens
      (IOL) on visible light-induced lesion in cultured retinal pigment epithelium
      (RPE). METHODS: It was a experimental study. A human retinal pigment epithelium
      cell line (ARPE-19) was used to study the protective role. Cells from the same
      passage were divided into the control, light exposure only, light exposure plus
      colorless IOL (FV-60A), light exposure plus photochromic IOL (BV-60A), light
      exposure plus yellow IOL (Acrysof Natural IOL) groups. The treatments were
      performed when the cells grew to 90% confluency. All cells were irradiated with
      visible light at an illumination intensity of 60 000-61 000 lux. After the
      treatments, we assessed 1: cells' viability by methyl thiazolyl tetrazolium (MTT)
      assay; 2: the extent of apoptosis by terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling (TUNEL), observing changes in the ultrastructure
      by transmission electron microscopy (TEM), and performing Hoechst staining to
      measure the apoptosis index (AI); 3: examining vascular endothelial growth factor
      (VEGF) and pigment epithelium-derived factor (PEDF) levels in the culture medium
      by enzyme linked immunosorbent assay (ELISA). RESULTS: Measurements of the cell
      viability of the five groups were (0.61 +/- 0.01), (0.39 +/- 0.01), (0.46 +/-
      0.01), (0.57 +/- 0.01), and (0.58 +/- 0.02), respectively. Apoptosis was
      significantly activated by visible light as observed in TUNEL staining and TEM.
      The AIs of the five groups were (0.99 +/- 0.65)%, (9.28 +/- 0.59)%, (6.54 +/-
      0.37)%, (4.69 +/- 0.74)%, and (2.72 +/- 0.67)%, respectively. The levels of VEGF
      in the five groups were (3931.64 +/- 25.26) ng/L, (5459.38 +/- 42.69) ng/L,
      (4800.55 +/- 42.12) ng/L, (4561.21 +/- 46.27) ng/L, and (4420.35 +/- 28.66) ng/L,
      respectively. The levels of PEDF in the five groups were (182.85 +/- 1.68) ug/L,
      (156.52 +/- 0.64) ug/L, (155.57 +/- 3.43) ug/L, (167.57 +/- 2.88) ug/L, and
      (170.90 +/- 2.99) ug/L, respectively. Comparing the photochromic IOL group with
      the yellow IOL group, there was no difference in cell viability (q = 0.94) and
      PEDF levels (q = 1.51) (P > 0.05), but there was a significant difference between
      the AI (q = 5.04) and VEGF levels (q = 6.78) (P < 0.05). Comparing the
      photochromic IOL group with the colorless IOL group, there were significant
      differences in cell viability (q = 18.92) , AI (q = 4.78) , VEGF (q = 11.52) and
      PEDF levels (q = 4.96) (P < 0.05). CONCLUSIONS: Photochromic IOL can abate the
      degree of acute photodamage of RPE. The protective efficiency was the highest
      when using the yellow Acrysof Natural IOL, followed by photochromic IOL and
      colorless IOL.

PMID- 24021182
TI  - [Evaluation of quality of vision in early stage after sub-bowman keratomileusis].
AB  - OBJECTIVE: To assess the quality of vision in the early stage after sub-bowman
      keratomileusis (SBK) for the correction of moderate and high myopia. METHODS:
      Retrospective case series. Sixty eight myopic eyes of 35 consecutive patients in
      Chongqing Medal Eye Institute from May to November 2011 were enrolled in this
      study. All patients were evaluated at 2 weeks, 1 and 3 months postoperatively.
      The main measurements included visual acuity, corneal and total optical wavefront
      aberration, photopic and mesopic contrast sensitivity. RESULTS: The median values
      of preoperative uncorrected central visual acuity (UCVA) and best corrected
      visual acuity (BCVA) were 0.05 and 1.00, respectively. The median value of
      postoperative UCVA was 1.20. There was no significant difference between the
      preoperative and postoperative anterior corneal total aberration (F = 0.712, P >
      0.05). Compared with preoperative value (0.47 +/- 0.17)um, the corneal high
      orders aberrations in 2 weeks after SBK (1.37 +/- 0.72) um increased by 3 times.
      The total optical aberrations in 2 weeks after SBK (0.99 +/- 0.58) um decreased
      to one-eighth of preoperative measurements (8.26 +/- 2.93) um. Compared with
      preoperative value (0.30 +/- 0.12)um, the total high order aberrations in 2 weeks
      after SBK (0.46 +/- 0.19) um increased by 1.5 times. Although photopic and
      mesopic contrast sensitivity fluctuated mildly after SBK, the measurements did
      not decline significantly. Compared with preoperative data, mesopic contrast
      sensitivity at 3 months increased 0.294 (F = 20.88,P < 0.01) and 0.296 (F =
      13.64, P < 0.01) at 12 and 18 c/d, respectively. CONCLUSION: Patients could
      obtain good quality of vision at the early stage after SBK.

PMID- 24021183
TI  - [Abnormal epithelial differentiation and tear film alteration in pterygium].
AB  - OBJECTIVE: To investigate the differentiation and proliferation of the
      conjunctival epithelium and tear film function in pterygia. METHODS: It was a
      retrospective study. Fifteen patients (15 eyes) who underwent excision for
      pterygium were enrolled in this study. Immunostaining for K10, K14, K19, MUC5AC,
      K16, Ki67 and P63 was performed on the pterygial epithelium and normal
      conjunctival epithelium. Schirmer I test was performed, and the tear film break
      up time (BUT) was evaluated just prior to and 6 months after surgery. Multi
      factor regression analysis was assessed to observe if there is a correlation
      between pterygial growth and tear film function. RESULTS: The average absorbency
      of K19 and MUC5AC immuno-staining all significantly changed (3727.86 +/- 2544.73
      vs. 25 528.00 +/- 12 901.06, 2080.48 +/- 2340.17 vs. 7182.51 +/- 3069.20, t =
      9.261,3.538, P < 0.05), and increased in K10 and K14 in patients with pterygia
      compared with normal conjunctivae keratin (2017.51 +/- 2114.3 vs. 0, 6027.5 +/-
      1058.32 vs. 2123.28 +/- 1249.09, t = -6.151, P < 0.05). Furthermore, pterygial
      epithelium showed activated proliferation, evidenced by significantly up
      regulated expression of K16, P63 and Ki67 compared to normal control. The
      Schirmer I test did not indicate any significant differences pre- and post
      operatively. However, the BUT was significantly prolonged 1 month post surgery
      compared to pre-surgery (t = -4.222, P < 0.05). CONCLUSION: This study indicates
      that abnormal epithelial differentiation and proliferation are present in
      pterygium , which is characterized by squamous metaplasia, accompanied with
      instability of tear film and normal basic tear secretion.

PMID- 24021184
TI  - [Characteristics of choroidal melanoma in contrast-enhanced ultrasonography].
AB  - OBJECTIVE: To investigate the characteristics of choroidal melanoma in contrast
      enhanced ultrasonography. METHODS: Case-control study.From October 2007 to
      December 2008, 21 choroidal melanoma patients (21 eyes) were treated in Beijing
      Tongren Hospital,including 13 males and 8 females with average age at 57 years
      (ranged from 18 to 76 years).Fourteen cases (14 eyes) of choroidal hemangioma
      treated during the same period, including 9 males and 5 females, with average age
      at 51 years(ranged from 24 to 71 years) were selected for the comparison.All
      patients were examined with contrast-enhance ultrasound, the contrast agent
      (sulfur hexafluoride) was injected into elbow vein,continuous recording of
      contrast agent in the lesions was conducted from filling to subside stages.
      Sonoliver software was used to analyze the imaging process.Logistic regression
      was used to compare the data collected from choroidal melanoma and hemangioma to
      develop a differential diagnosis equation for the diagnosis of choroidal
      melanoma. RESULTS: Contrast-enhanced ultrasonography in choroidal melanoma showed
      the following characteristics: the lesions were completely filled with the
      contrast reagent,the typical filling process began from the peripheral area to
      the center,filling defects were found in some cases,filling time in the melanoma
      was later than that in the normal tissues and faded early than that in the normal
      tissues. Quantitative analysis in choroidal melanoma lesions showed that the time
      to peak of contrast material [(22.80 +/- 9.85)s] was less than that in the
      control group [(29.57 +/- 24.76)s], maximum intensity [(191.31 +/- 146.90)%] was
      greater than that in the control group [(100.00 +/- 0.00)%]; rising time [(18.52
      +/- 7.09)s] was less than that in the control group [(26.45 +/- 21.83)s] and mean
      transit time [(63.56 +/- 26.04)s] was less than that in the control group
      [(149.87 +/- 182.68)s]. The differences of maximum intensity and mean transit
      time between the melanoma and the controls were statistically significant (t = 
      2.848,2.197; P < 0.01). Logistic regression equation using the maximum intensity
      and mean transit time parameters could distinguish choroidal melanoma and
      hemangioma with a sensitivity at 90.5% (19/21) and specificity at 12/14.
      CONCLUSIONS: Contrast-enhanced ultrasonography is a new method for the diagnosis
      of malignant tumors in the eye. Contrast-enhanced ultrasonography combining with
      quantitative analysis can be helpful for the diagnosis and different diagnosis of
      choroidal melanoma.

PMID- 24021185
TI  - [Inhibitory effects of doxycycline on argyrophilic nucleolar organizing regions
      and a-smooth muscle actin expression in proliferative bovine corneal
      myofibroblasts in vitro].
AB  - OBJECTIVE: To investigate the effect of doxycycline on the nucleolar organizing
      regions and a-smooth muscle actin expression in bovine corneal myofibroblasts in
      vitro and assess its contribution to ocular surface repair mechanisms. METHODS:
      Cell culture and identification: bovine corneal fibroblasts were cultured after
      the stroma was incubated in 1.0 and 2.0 g/L type I collagenase in two
      stages.Isolated cells were plated at mantaryay culture flask in 10% of BSA RPMI
      1640. Vimentin and alpha-smooth muscle actin (alpha-SMA) organization were
      evaluated by immunocytochemistry. The cells staining positive for Vimentin and
      alpha-SMA indicated the presence of corneal myofibroblasts. Bovine corneal
      myofibroblasts were treated with different concentrations of doxycycline (10, 20,
      40, 60, 80 mg/L) , a bland control group and the dexamethasone group (120 mg/L)
      were set up, each group had 30 cases. The argyrophilic nucleolar organizing
      regions (AgNOR) staining and the immunohistochemistry for alpha-SMA were
      performed when the cells were treated for 24 hours and 48 hours. The AgNOR count
      (Ag-c), AgNOR area (Ag-a) and the expression of alpha-SMA in the bovine corneal
      myofibroblasts among each experiment group and control group were compared using
      one-way ANOVA, further pairwise comparisons using Independent-Samples t test.
      RESULTS: Cell culture techniques were successfully used to establish a method for
      the isolation and culture of bovine corneal myofibroblasts. Microscopic
      examination and immunohistochemical staining confirmed that the cells cultured
      were bovine corneal myofibroblasts. The Ag-c and Ag-a of bovine corneal
      myofibroblasts progressively decreased as the concentrations of doxycycline was
      increase. 24 h:bland control group Ag-c was 6.40 +/- 0.6, 60 mg/L doxycycline
      group Ag-c was 2.23 +/- 0.43;bland control group Ag-a was (34.80 +/- 2.36) um(2),
      60 mg/L doxycycline hormone group Ag-a was (19.91 +/- 2.15) um(2). 48 h: bland
      control group Ag-c was 7.27 +/- 0.6,60 mg/L doxycycline hormone group Ag-c was
      2.80 +/- 0.76, bland control group Ag-a was (36.27 +/- 1.99) um(2), 60 mg/L
      doxycycline group Ag-a was (13.75 +/- 2.09) um(2). The differences were
      statistically significant: in the same time intervention (FAg-c 24 h = 252.55,
      FAg-a 24 h = 202.16, P < 0.05, FAg-c 48 h = 169.38, FAg-a 48 h = 853.23, P <
      0.05), in the same concentrations intervention (tAg-c = 6.98, tAg-a = 11.62, P <
      0.05). And 60 mg/L of doxycycline had an obviously inhibitory action as 120 mg/L
      dexamethasone in the same treated hours (dexamethasone group Ag-a 24 h = 30.56 +/
      3.66, dexamethasone group Ag-a 48 h = 28.35 +/- 1.23 ),the differences were not
      statistically significant (tAg-a 24h = 1.182, P = 0.242,tAg-a 48 h = 0.21, P =
      0.832). As the concentrations investigated, doxycycline can inhibit the
      expression of alpha-SMA in the bovine corneal myofibroblasts (189.90 +/- 7.48,
      140.20 +/- 7.79, 113.20 +/- 8.98, 98.00 +/- 3.50, 85.50 +/- 4.99), the difference
      was statistically significant (F = 761.79, P = 0.00). While dexamethasone had no
      significant role in the expression of alpha-SMA (bland control group was 225.10
      +/- 6.74, the dexamethasone group was 228.50 +/- 7.12), and the statistically
      difference was not obvious (t = 1.096, P = 0.287). CONCLUSIONS: As the
      concentrations of doxycycline was increased from 10 mg/L to 80 mg/L, the AgNOR
      count and AgNOR area of bovine corneal myofibroblasts can be significantly
      reduced in vitro. Compared with dexamethasone, doxycycline significantly
      suppressed the expression of alpha-SMA in bovine corneal myofibroblasts in a dose
      dependent positive trend.

PMID- 24021186
TI  - [Influence of 460-480 nm wavelength light at three different irradiance on retina
      tissue of SD rats].
AB  - OBJECTIVE: To investigate the survival of SD rat retinal cells after irradiated
      with 460-480 nm wavelength blue light at three different irradiance. METHODS:
      Experimental study. Seventy-six SD rats six weeks old were divided into control
      group (4 animals) and experimental groups (18 different subgroups) with 4 animals
      for each group. Healthy SD rats were exposed to the 460-480 nm blue light for 3
      or 12 hours on three different irradiance of 0.6, 1.5 and 10.0 W/m(2)
      respectively. After recovery in darkness for 4 hours, 24 hours or 3 days, retinal
      tissue was collected after the eyes were enucleated. Hematoxylin-eosin staining
      was performed to evaluate the general anatomical changes of the rat retinal
      layers. TdT-mediated dUTP nick-end labeling was performed to detect apoptotic
      cells and immunofluorescence staining was conducted to illustrate the expression
      and location of related proteins in Muller cells. The number of ganglion cells
      was analyzed by one-way ANOVA. RESULTS: No injury was observed in SD rat retina
      at the irradiance of 0.6 W/m(2). Retinal cells were damaged with irradiance at
      10.0 W/m(2), which mainly affected photoreceptors and retinal pigment epithelial
      cells, while Muller cells of retinal inner nuclear layer were also involved.
      Apoptosis began after 4 hours of exposure and peaked at 24 hours. Moderate damage
      of retina was observed at the irradiance of 1.5 W/m(2) after 12 hours rather than
      3 hours exposure. The number of ganglion cells was significantly different among
      the different groups 3 days after exposure. When the exposure time was 3 hours,
      the number of retinal ganglion cells under different irradiance at 0.0, 0.6, 1.5
      and 10.0 W/m(2) was respectively 41.42 +/- 0.17, 40.58 +/- 0.50, 40.92 +/- 0.32
      and 22.83 +/- 0.79 (F = 1305.86, P = 0.000). When the exposure time was 12 hours,
      the number of retinal ganglion cells under different irradiance at 0.0, 0.6, 1.5
      and 10.0 W/m(2) was respectively 41.42 +/- 0.17, 40.83 +/- 0.69, 41.08 +/- 0.17
      and 22.75 +/- 0.83 (F = 1095.78, P = 0.000). The number of retinal ganglion cells
      showed significant decrease 3 days after exposure at the irradiance 10.0 W/m(2)
      (exposure time 3 h:t = 52.32, P = 0.000; exposure time 12 h:t = 47.58, P =
      0.000). CONCLUSIONS: The safe exposure time to SD rat retina layers is 12 hours
      for the blue light with wavelength 460-480 nm at the irradiance 0.6 W/m(2). And
      the safe exposure time descends to 3 hours at the irradiance 1.5 W/m(2).

PMID- 24021187
TI  - [Recent advances in femtosecond laser-assisted cataract surgery].
AB  - As the leading cause of blindness, the type of surgery performed to remove
      cataracts has evolved from Intracapsular to Extracapsular and to
      phacoemulsification. Advantages of femtosecond laser include high instantaneous
      power, strong penetration, short pulse-duration and micro-precision present
      superior accuracy, predictability and safety to cataract surgery, while also
      minimizing injury to surrounding ocular tissue. It mainly assists in the
      procedures of anterior capsulotomy, lens fragmentation, clear corneal incision
      and limbal relaxing incision creation. However, compared to conventional
      phacoemulsification, problems such as the minimization of complications and
      difficulties in conducting peer-reviewed studies with a longer follow-up period
      and large sample, as well as coverage of added costs remain untracked.The purpose
      of this review is to outline the advantages and disadvantages as well as clinical
      value of this evolving technology compared to conventional phacoemulsification. 

PMID- 24021188
TI  - [Research relating the use of systematic drug and cataracts].
AB  - Cataract is the leading cause of blindness in the world. The use of certain drugs
      is one of the risk factors for lens opacities, such as glucocorticoids and
      chlorpromazine. We reviewed new studies regarding the relationship between
      cataract formation and drugs that have become more widely used in recent years,
      such as statins, anti-epileptic drugs, antidepressants, tamoxifen, amiodarone,
      eltrombopag, isotretinoin, nifedipine and quetiapine. We hope this review could
      offer suggestions and reference for clinical doctors.

PMID- 24021189
TI  - [Integrated therapy of congenital cataract to prevent blindness and low vision].
AB  - Congenital cataract is a major cause of treatable blindness in the pediatric
      population worldwide. Advances in microsurgical techniques have significantly
      increased the success rate of surgery. However, visual rehabilitation outcomes
      are not always satisfactory even after a successful surgery. Due to delayed
      surgery, irrational aphakic correction, and lack of amblyopic training, a large
      number of infants in China remain blind or low-visioned after cataract surgery.
      Appropriate timing of surgical intervention, rational surgical methodology as
      well as systematic optical correction and amblyopic training are critical for the
      prevention of blindness and low vision in congenital cataract. 

PMID- 24021190
TI  - Baseline sensitivity of HSV-1 and HSV-2 clinical isolates and defined acyclovir
      resistant strains to the helicase-primase inhibitor pritelivir.
AB  - Fifty-nine US isolates of HSV-1 and HSV-2 obtained between 1998 and 2004 were
      tested for sensitivity to the helicase-primase inhibitor, pritelivir (AIC316, BAY
      57-1293) by plaque-reduction assay. All isolates, which were collected prior to
      any clinical use of primase-helicase inhibitors, were sensitive and showed mean
      EC50 values of 0.026 and 0.029MUM for HSV-1 and HSV-2, respectively. Furthermore,
      several laboratory-selected acyclovir-resistant HSV mutants were also sensitive
      to pritelivir. These data provide a baseline for HSV sensitivity to pritelivir in
      general population before it is introduced and broadly used to treat HSV
      infection. The data also validate pritelivir as an appropriate therapy for
      nucleoside-resistant HSV infections. 

PMID- 24021191
TI  - Ventilation and cardiac related impedance changes in children undergoing
      corrective open heart surgery.
AB  - Electrical impedance tomography (EIT) can determine ventilation and perfusion
      relationship. Most of the data obtained so far originates from experimental
      settings and in healthy subjects. The aim of this study was to demonstrate that
      EIT measures the perioperative changes in pulmonary blood flow after repair of a
      ventricular septum defect in children with haemodynamic relevant septal defects
      undergoing open heart surgery. In a 19 bed intensive care unit in a tertiary
      children's hospital ventilation and cardiac related impedance changes were
      measured using EIT before and after surgery in 18 spontaneously breathing
      patients. The EIT signals were either filtered for ventilation (DeltaZV) or for
      cardiac (DeltaZQ) related impedance changes. Impedance signals were then
      normalized (normDeltaZV, normDeltaZQ) for calculation of the global and regional
      impedance related ventilation perfusion relationship (normDeltaZV/normDeltaZQ).
      We observed a trend towards increased normDeltaZV in all lung regions, a
      significantly decreased normDeltaZQ in the global and anterior, but not the
      posterior lung region. The normDeltaZV/normDeltaZQ was significantly increased in
      the global and anterior lung region. Our study qualitatively validates our
      previously published modified EIT filtration technique in the clinical setting of
      young children with significant left-to-right shunt undergoing corrective open
      heart surgery, where perioperative assessment of the ventilation perfusion
      relation is of high clinical relevance. 

PMID- 24021192
TI  - Effects of zileuton on airway smooth muscle remodeling after repeated allergen
      challenge in brown Norway rats.
AB  - BACKGROUND: Chronic asthma is characterized by airway inflammation and
      remodeling. OBJECTIVE: This study aimed to evaluate the effects of zileuton on
      bronchial hyperresponsiveness, airway inflammation and airway smooth muscle (ASM)
      remodeling. METHODS: Two experimental groups of brown Norway rats sensitized and
      repeatedly challenged with aerosolized ovalbumin (OA) were given oral zileuton
      (OA-zileuton group) and oral saline only (OA-saline group). A third, control
      group was sensitized and challenged by saline. The rats were anesthetized and
      paralyzed. Pulmonary function tests were performed at baseline and after varying
      doses of acetylcholine. Bronchoalveolar lavage fluid and lung tissues were
      examined. RESULTS: Zileuton had beneficial effects on pulmonary function, airway
      inflammation and ASM remodeling in the OA-zileuton group compared to the OA
      saline group. Zileuton inhibited an OA-stimulated increase in ASM by inhibiting
      hypertrophy, hyperplasia and increased extracellular matrix via the
      phosphatidylinositol 3-kinase (PI3K)/Akt pathway, thereby reducing cyclin D1
      expression and attenuating bronchial hyperresponsiveness. CONCLUSION: OA
      increases airway inflammation and ASM mass. Zileuton effectively prevents
      bronchial hyperresponsiveness, airway inflammation and ASM remodeling in
      sensitized rats through the PI3K/Akt pathway, which reduces cyclin D1 expression.

PMID- 24021194
TI  - [Immediate implant placement: right or wrong].

PMID- 24021193
TI  - Environmental triggers of autoimmunity in anti-synthetase syndrome: the lungs
      under the spot light.
AB  - The prevalence of interstitial lung involvement in anti-synthetase syndrome (anti
      SS) may be as high as 70% and is a major contributor to morbidity and mortality.
      Histidyl-tRNA synthetase (Jo-1) is the most common autoantigenic target among the
      aminoacyl-tRNA synthetases. We report two well documented anti-SS cases where it
      was observed significant exposure to a known inhaled offending antigen,
      development of a lymphocytic interstitial lung disease (ILD) and negative auto
      antibodies, interpreted at first as hypersensitivity pneumonitis. Only after 14
      and 30 months, respectively, the development of systemic symptoms compatible with
      anti-SS and anti-Jo-1 was observed. A growing body of evidence suggests that the
      lungs are the environment in which Jo-1 autoimmunity may be initiated and
      propagated. The description of the clinical and laboratorial evolution of these
      patients together with accumulated evidence of biological plausibility support
      the hypothesis that anti-SS can follow an episode of lung inflammation secondary
      to inhaled antigen exposure. 

PMID- 24021195
TI  - [Decision-making on the timing of implant placement in anterior zones:immediate
      or early implant placement].

PMID- 24021196
TI  - [Immediate implant placement: evaluation and application].

PMID- 24021197
TI  - [Clinical experience of immediate implant placement in the anterior maxilla].

PMID- 24021198
TI  - [Comparative study on the morphology of crown, alveolar ridge crest and gingival
      in maxillary anterior region].
AB  - OBJECTIVE: To investigate the correlation among the morphology of crown, alveolar
      ridge crest and gingiva in maxillary anterior region of adults and to provide
      anatomical basis for clinical implant esthetics. METHODS: Sixty Han-Chinese with
      healthy peridontium were selected in this study. The curvature of labial alveolar
      crest, the length and height of inter-proximal bone were measured on 3-D model
      reconstructed from cone-beam CT (CBCT) images, and the curvature of free gingiva,
      the width and height of inter-dental papilla and central incisor crown were
      evaluated on casts. The ratio of crown width to height was ranked and the 10
      ranked highest were categorized as group Short-Wide (SW), the 10 ranked lowest
      were selected as group Long-Narrow (LN). RESULTS: In maxillary anterior region,
      the curvature angle of both alveolar crest and marginal gingiva were
      significantly different among different tooth regions, but the alveolar and
      gingival curvature was significantly correlated in the same region (P < 0.05).
      The morphology of inter-proximal bone and papilla was significantly correlated (P
      < 0.01), except the region between central and lateral incisors (P = 0.625, P >
      0.05). Compared to group SW, group LN formed a pronounced scalloped contour of
      gingival margin (P = 0.002) and slender inter-dental papilla (P = 0.000).
      CONCLUSIONS: The free gingival curvature and inter-dental papillary morphology
      are significantly correlated with the morphology of crown and alveolar ridge
      crest in maxillary anterior region of Han-Chinese. Individuals with long-narrow
      crown, pronounced scalloped marginal gingiva and slender inter-dental papilla are
      susceptible to risk implant esthetics.

PMID- 24021199
TI  - [Clinical study of immediate post-extraction implant and immediate function in
      edentulous patients].
AB  - OBJECTIVE: To evaluate the outcomes of immediate post-extraction implant and
      immediate function according to All-on-4 immediate concept in edentulous
      patients. METHODS: The study included 46 patients with hopeless teeth. A total of
      254 implants were immediately inserted after extraction and 56 fixed complete
      arch all-acrylic prostheses finished and functioned on the day of extraction from
      June 2008 to March 2012 in Peking University School of Stomatology. At time of
      abutments connection, a panoramic radiograph was taken, and radiographic
      assessment of the marginal bone level was performed in every 6 months. Marginal
      bone level, integrity of the restoration, survival of the implants and degree of
      satisfaction of the patients were evaluated. RESULTS: A total of 254 implants
      were immediate loading. Thirteen implants were lost 6 - 8 weeks after immediate
      loading and the survival rate of 94.9% (241/254). The marginal bone absorption
      was (0.7 +/- 0.3) mm on average. All patients were satisfied with the clinical
      results. CONCLUSIONS: Immediate post-extraction implant and immediate function
      technique can be a predictable technique. Further study is needed to determine
      the long-term results of the technology.

PMID- 24021200
TI  - [Classification of anterior maxillary incisor root and housing alveolar crest in
      relation to the implant treatment plan].

PMID- 24021201
TI  - [Immediate implant esthetic restoration in maxillary anterior tooth: a 5-year
      clinical result].

PMID- 24021202
TI  - [Effect of periodontal treatment on long-term prognosis of dental implants].

PMID- 24021203
TI  - [Summary of immediate implant or delayed immediate implant].

PMID- 24021204
TI  - [Effect of bioactive glasses on angiogenic growth factors of human dental pulp
      cells].
AB  - OBJECTIVE: To investigate the effects of bioactive glasses (BG) including 45S5
      and nano-58S on proliferation, angiogenic markers vascular endothelial growth
      factor (VEGF) and basic fibroblast growth factor (bFGF) secretion and gene
      expression of human dental pulp cells (HDPC). METHODS: HDPC of 4th passage were
      cultured in Dulbecco's modified Eagle's medium (DMEM) which contained 0.1 g/L
      45S5 or nano-58S ionic dissolution products. Meanwhile HDPC were cultured in DMEM
      without BG as control group. Proliferation of the cells was evaluated with methyl
      thiazolyl tetrazolium (MTT) assay on day 1, 2, 3. Quantitative real-time PCR and
      quantitative sandwich enzyme immunoassays were used to test VEGF and bFGF gene
      expression and protein secretion of HDPC on day 1, 2, 3. RESULTS: The relative
      growth rate (RGR) of 45S5 and nano-58S groups were (134.5 +/- 5.0)% and (146.3 +/
      19.8)%, which was significantly different from that of control group (P < 0.05).
      The quantity of VEGF secretion of two experimental groups were (189.29 +/- 4.64)
      and (216.18 +/- 14.67) ng/L, respectively, significantly higher than that of the
      control group [(159.03 +/- 11.69) ng/L] (P < 0.05). Furthermore, the nano-58S
      group secreted much more VEGF than 45S5 group (P < 0.05).bFGF secretion of HDPC
      was also enhanced by both 45S5 and nano-58S bioactive glasses. The VEGF gene
      expression of 45S5 and nano-58S on day 1 were (1.70 +/- 0.19) and (1.63 +/-
      0.42), while the bFGF gene expressin on day 3 were (1.49 +/- 0.02) and (2.30 +/-
      0.04), all significantly higher than that of control group (P < 0.05).
      CONCLUSIONS: Bioactive glasses can enhance the proliferation, VEGF and bFGF
      secretion and gene expression of human dental pulp cells. Compared with 45S5,
      nano-58S showed a higher activation.

PMID- 24021205
TI  - [Inhibitory effect of a novel crosslinking quaternary ammonium methacrylates on
      matrix metalloproteinases].
AB  - OBJECTIVE: To evaluate the anti-matrix metalloproteinase (MMP) activity of a
      novel crosslinking quaternary ammonium methacrylates, 2-methacryloxylethyl
      dodecylmethyl ammonium bromide (MAE-DB). METHODS: The effects of MAE-DB at
      different concentrations (1%, 3%, 5%, 7%) on soluble matrix metalloproteinase-8
      (MMP-8) were investigated using fluorescent assay kit. Readings were taken every
      20 min for 3 h. The 1, 10-phenanthroline provided by the assay kit served as
      control group. Demineralized dentin beams were randomly divided into three groups
      (n = 50) and immersed in different solutions: artificial saliva, MAE-DB
      incorporated artificial saliva and chlorhexidine incorporated artificial saliva.
      After temperature cycling, the changes of ultimate tensile strength were measured
      to determine the effect of MAE-DB on the activity of matrix-bound endogenous
      matrix metalloproteinases. The morphology of dentin collagen fibrils in the three
      groups was observed via transmission electron microscopy (TEM). RESULTS: MAE-DB
      could effectively inhibit the activity of soluble MMP-8. The inhibition
      percentage of 3% MAE-DB was 99.53% after 1 h, and it was significantly higher
      than that of 1, 10-phenanthroline (95.71%, P < 0.05). After temperature cycling,
      the ultimate tensile strengths of MAE-DB groups were significantly higher than
      those of the artificial saliva groups and the chlorhexidine groups (P < 0.05).
      TEM micrographs of MAE-DB group revealed that the microstructure of the collagen
      fibrillar was intact, while the fibrillar in the artificial saliva group was
      disrupted, indicating a protective function of MAE-DB on dentin collagen.
      CONCLUSIONS: MAE-DB can inhibit the activity of MMP and protect dentin collagen
      from enzyme degradation.

PMID- 24021206
TI  - [The durability of three self-etch adhesives bonded to dentin].
AB  - OBJECTIVE: To investigate the durability of self-etch adhesives bonded to dentin
      in vitro. METHODS: Forty-two extracted human molars were selected and occlusal
      dentin surfaces were exposed. The teeth were randomly distributed into three
      groups based on adhesives applied. The one-step self-etch adhesive B(Adper
      Prompt) and C(G-Bond) and two-step self-etch adhesive A (Clearfil SE bond) were
      used. After application of the adhesives to the dentin surfaces, composite crowns
      were built up, after 24 h water storage, the teeth were sectioned longitudinally
      into sticks (1.0 mm*1.0 mm bonding area) for microtensile testing or slabs (1 mm
      thick) for scanning electron microscopec (SEM) observation. Bonding strength
      (mTBS) and nano-leakage were evaluated immediately after cutting or after 6
      months in water. The mTBS was analyzed using one-way ANOVA (SPSS 13.0). The
      nanoleakage was observed by SEM with a backscattered electron detector. RESULTS:
      Both adhesives and water storage time affected the mTBS. All adhesives showed
      decreased bond strength after six-month water aging [A dropped from (40.60 +/-
      5.76) MPa to (36.04 +/- 3.15) MPa; B dropped from (19.06 +/- 1.50) MPa to (11.19
      +/- 1.97) MPa; C dropped from (17.75 +/- 1.10) MPa to (9.14 +/- 1.15) MPa] (P <
      0.05). B and C showed lower mTBS than A after aging (P < 0.05). Compared to A,
      nanoleakage was more obvious after aging for B and C. CONCLUSIONS: All self-etch
      adhesives tested were probably influenced by water aging, however, the two-step
      adhesive showed better durability than the one-step adhesives.

PMID- 24021207
TI  - [Repeatability of three-dimensional measurements based on cone-beam CT images].
AB  - OBJECTIVE: To investigate the repeatability of three-dimensional (3-D)
      cephalometric measurements for the clinical application of 3-D cephalometry.
      METHODS: Forty-nine measurements that widely used in traditional cephalometric
      analyses were defined in 3-D cone-beam CT (CBCT) images. Three examiners
      identified landmarks on CBCT images of 17 subjects with normal occlusion,
      respectively, and 3-D measurements were exported automatically by software
      SimPlant. Inter-examiner reliability correlation coefficients (ICC) were obtained
      for all measurements. RESULTS: Repeatability of 36 measurements was high (ICC
      value greater than 0.9), including SNA, SNB. Repeatability of 11 measurements was
      moderate (ICC value between 0.8 and 0.9), including CoL-GoL, CoL-MSP.
      Repeatability of 2 measurements was low (ICC value lower than 0.8), including Gn
      MSP and MPR-MSP. CONCLUSIONS: Most 3-D cephalometric measurements based on CBCT
      had high repeatability. However, some 3-D cephalometric measurements had limited
      repeatability.

PMID- 24021208
TI  - [Formulation and evaluation of evidence-based clinical practice guideline: III.
      Appraisal of evidence-based clinical practice guidelines].

PMID- 24021209
TI  - Learning to deal constructively with troubled conscience related to care
      providers' perceptions of not providing sufficient activities for residents.
AB  - The aim of this study was to illuminate an intervention process to assist care
      providers in municipal care of older people to constructively deal with their
      troubled conscience generated from their perceived shortcomings about not
      providing sufficient activities for residents. The study design was grounded in
      participatory action research. Twelve care providers and their manager
      participated in intervention sessions. Content analysis was used to analyze the
      transcriptions. By sharing their experiences with each other, care providers
      became aware of, and confirmed in one another, what types of activities were
      meaningful for residents and actions were taken to provide such activities. The
      importance of being attentive and relying on residents' responses, that is,
      providing person-centered activities, was found to be satisfying to residents and
      eased the care providers' troubled conscience. An enlightened conscience can be
      an important asset, which may prevent ill-health and improve quality of care. 

PMID- 24021210
TI  - The relationship between social support and adherence to healthy lifestyle among
      patients with coronary artery disease in the north of Jordan.
AB  - Numerous studies have shown that social support improves health behaviors in
      patients with coronary artery disease (CAD). The purpose of this study was to
      examine the relationship between adherence to a healthy lifestyle, and social
      support and selected sociodemographics among patients with CAD. Cross-sectional
      descriptive design was used. A convenient sample of 153 patients with CAD was
      recruited from the cardiac clinic in an educational hospital in the north of
      Jordan. One hundred and thirty-three patients completed the interview. Social
      support was the most significant predictor-t(124) = 9.51, p < .001-which
      explained 60% of variance in adherence to a healthy lifestyle. Providing patients
      with adequate social support improves adherence to a healthy lifestyle. More
      attention should be given to the elderly and patients with low income to enhance
      adherence to a healthy lifestyle. The applications of this study in practice
      provide a guide for nursing clinical assessment of social support for patients
      facing CAD. 

PMID- 24021211
TI  - Genital self-mutilation in a suicide attempt: a rare sequela of a hypochondriacal
      delusion of infection with HIV.
AB  - Genital self-mutilation is mostly seen among psychotic, affective and gender
      identity disorder(s). We present here a rare case report of such genital self
      mutilation in a person with a hypochondriacal delusion of infection with HIV
      precipitated by erroneous and anxiety-provoking miscommunication during HIV
      testing. Such cases remind us of the need for systematic and appropriate pre-test
      and post-test HIV counseling, to help prevent such outcomes. 

PMID- 24021212
TI  - Response to Dikkers letter to the editor regarding "systematic review of
      intralesional cidofovir dosing regimens in the treatment of recurrent respiratory
      papillomatosis".

PMID- 24021213
TI  - Phosphohistone H3 and Ki-67 labeling indices in cytologic specimens from well
      differentiated neuroendocrine tumors of the gastrointestinal tract and pancreas:
      a comparative analysis using automated image cytometry.
AB  - BACKGROUND: Ki-67 proliferation index was recently incorporated in the grading of
      neuroendocrine neoplasms (NENs) of the gastrointestinal tract (GIT) and pancreas.
      These are now divided into well-differentiated neuroendocrine tumors (WDNETs,
      grades 1 and 2) and poorly differentiated neuroendocrine carcinomas (grade 3).
      While Ki-67 is an established proliferation marker in NENs, phosphohistone H3
      (PHH3), a newer marker of mitotic activity, is not. METHODS: We determined Ki-67
      and PHH3 indices on cytologic samples from WDNETs of the GIT and pancreas using
      an automated cellular imaging system (ACIS(r)). RESULTS: There was a strong
      correlation between Ki-67 and PHH3 indices generated by ACIS on cytologic
      samples. However, in some cases the two stains caused conflicting grades within
      the same tumor. CONCLUSION: Both antibodies stain cells in different phases of
      the cell cycle which may cause discordant grades, thus affecting patient
      management and prognostication. Ki-67 staining is stronger than PHH3, making 'hot
      spots' easier to identify on ACIS. Ki-67 is more ideal than PHH3 for staining
      NENs, especially in tumors with borderline grades. Because PHH3 generates lower
      mitotic indices it should not be used as a proliferation marker in NENs until its
      expression has been further characterized.

PMID- 24021215
TI  - Molecular pharmacology of ABCG2 and its role in chemoresistance.
AB  - The ATP-binding cassette, subfamily G, isoform 2 protein (ABCG2) is an important
      member of the ABC transporter superfamily, which has been suggested to be
      involved in multidrug resistance (MDR) in cancer. Its diverse range of substrates
      includes many common chemotherapeutics such as imatinib, doxorubicin, and
      mitoxantrone. Physiologically, ABCG2 is highly expressed in areas such as the
      blood-brain barrier and gastrointestinal tract, where it is thought to play a
      role in protection against xenobiotic exposure. High ABCG2 expression has also
      been found in a variety of solid tumors and in hematologic malignancies and has
      been correlated with poorer clinical outcomes. Furthermore, ABCG2 expression is a
      characteristic feature of cancer stem cells, which are able to self-renew and
      differentiate. These cancer stem cells have been postulated to play an important
      role in MDR, where their inherent ABCG2 expression may allow them to survive
      chemotherapy and repopulate the tumor after exposure to chemotherapeutics. This
      observation raises the exciting possibility that by inhibiting ABCG2, cancer stem
      cells and other cancers may be targeted and eradicated, at which point
      conventional chemotherapeutics would be sufficient to eliminate the remaining
      tumor cells. Inhibitors of ABCG2, such as tyrosine kinase inhibitors,
      phosphodiesterase-5 inhibitors, and the fumitremorgin-type indolyl
      diketopiperazine, Ko143 [(3S,6S,12aS)-1,2,3,4,6,7,12,12a-octahydro-9-methoxy-6-(2
      methylpropyl)-1,4-dioxopyrazino[1',2':1,6]pyrido[3,4-b]indole-3-propanoic acid
      1,1-dimethylethyl ester], could potentially be used for this purpose. However,
      these agents are still awaiting comprehensive clinical assessment.

PMID- 24021214
TI  - Structure-based ligand discovery targeting orthosteric and allosteric pockets of
      dopamine receptors.
AB  - Small molecules targeting allosteric pockets of G protein-coupled receptors
      (GPCRs) have a great therapeutic potential for the treatment of neurologic and
      other chronic disorders. Here we performed virtual screening for orthosteric and
      putative allosteric ligands of the human dopamine D3 receptor (D3R) using two
      optimized crystal-structure-based models: the receptor with an empty binding
      pocket (D3R(APO)), and the receptor complex with dopamine (D3R(Dopa)). Subsequent
      biochemical and functional characterization revealed 14 novel ligands with a
      binding affinity of better than 10 MUM in the D3R(APO) candidate list (56% hit
      rate), and 8 novel ligands in the D3R(Dopa) list (32% hit rate). Most ligands in
      the D3R(APO) model span both orthosteric and extended pockets and behave as
      antagonists at D3R, with compound 7 showing the highest potency of dopamine
      inhibition (IC50 = 7 nM). In contrast, compounds identified by the D3R(Dopa)
      model are predicted to occupy an allosteric site at the extracellular extension
      of the pocket, and they all lack the anchoring amino group. Compounds targeting
      the allosteric site display a variety of functional activity profiles, where
      behavior of at least two compounds (23 and 26) is consistent with noncompetitive
      allosteric modulation of dopamine signaling in the extracellular signal-regulated
      kinase 1 and 2 phosphorylation and beta-arrestin recruitment assays. The high
      affinity and ligand efficiency of the chemically diverse hits identified in this
      study suggest utility of structure-based screening targeting allosteric sites of
      GPCRs.

PMID- 24021216
TI  - Enhancing Quality in Psychiatry with Psychiatrists (EQUIPP)--results from a pilot
      study.
AB  - OBJECTIVES: To pilot a pharmacist-led, patient centered medication management
      program. DESIGN: Prospective, single arm trial. SETTING: Academic geriatric
      psychiatry outpatient clinic. PARTICIPANTS: Outpatients at least 65 years old,
      proxy available if demented, and on two or more psychiatric medications.
      INTERVENTION: A clinical pharmacist completed a baseline medication review and
      made evidence-based recommendations that were implemented by the pharmacist after
      discussion with the physician. The pharmacist made a minimum of monthly contact
      for 6 months to review medications and related issues. MEASUREMENTS: The primary
      outcome was the change in number of medication related problems over time (3 and
      6 months) as defined by a predetermined classification system. RESULTS: The mean
      age of the 27 patients was 75 years, 10 of whom required a proxy to participate.
      On average, patients had nine chronic conditions and were taking 14 medications.
      The mean number (SD; range) of medication related problems at baseline was 4.1
      (2.2; 0-8) and at 3 and 6 months were 3.6 (2.4, 0-9) and 3.4 (2.1; 0-8),
      respectively. Most follow-up problems were new (80% and 89% at 3 and 6 months,
      respectively). CONCLUSION: Using a pharmacist to deliver a medication management
      program was feasible and addressed existing problems. New problems, however,
      developed over a short interval (3-6 months), suggesting that ongoing
      intervention is required.

PMID- 24021217
TI  - Common selective serotonin reuptake inhibitor side effects in older adults
      associated with genetic polymorphisms in the serotonin transporter and receptors:
      data from a randomized controlled trial.
AB  - OBJECTIVE: Antidepressant side effects are a significant public health issue,
      associated with poor adherence, premature treatment discontinuation, and, rarely,
      significant harm. Older adults assume the largest and most serious burden of
      medication side effects. We investigated the association between antidepressant
      side effects and genetic variation in the serotonin system in anxious, older
      adults participating in a randomized, placebo-controlled trial of the selective
      serotonin reuptake inhibitor (SSRI) escitalopram. METHODS: Adults (N = 177) aged
      >= 60 years were randomized to active treatment or placebo for 12 weeks. Side
      effects were assessed using the Udvalg fur Kliniske Undersogelser side-effect
      rating scale. Genetic polymorphisms were putative functional variants in the
      promoters of the serotonin transporter and 1A and 2A receptors (5-HTTLPR [L/S +
      rs25531], HTR1A rs6295, HTR2A rs6311, respectively). RESULTS: Four significant
      drug-placebo side-effect differences were found: increased duration of sleep, dry
      mouth, diarrhea, and diminished sexual desire. Analyses using putative high-
      versus low-transcription genotype groupings revealed six pharmacogenetic effects:
      greater dry mouth and decreased sexual desire for the low- and high-expressing
      serotonin transporter genotypes, respectively, and greater diarrhea with the 1A
      receptor low-transcription genotype. Diminished sexual desire was experienced
      significantly more by high-expressing genotypes in the serotonin transporter, 1A,
      or 2A receptors. There was not a significant relationship between drug
      concentration and side effects nor a mean difference in drug concentration
      between low- and high-expressing genotypes. CONCLUSION: Genetic variation in the
      serotonin system may predict who develops common SSRI side effects and why. More
      work is needed to further characterize this genetic modulation and to translate
      research findings into strategies useful for more personalized patient care.

PMID- 24021218
TI  - Psychiatric correlates of alcohol and tobacco use disorders in U.S. adults aged
      65 years and older: results from the 2001-2002 National Epidemiologic Survey of
      Alcohol and Related Conditions.
AB  - OBJECTIVE: To examine associations of alcohol and tobacco use disorders and
      psychiatric conditions among older U.S. adults. METHODS: Sample was individuals
      aged at least 65 years (N = 8,205) who participated in the 2001-2002 National
      Epidemiologic Survey on Alcohol and Related Conditions. Measurements included
      lifetime and past 12-month Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition alcohol use disorders (AUDs), tobacco use disorders (TUDs), and
      psychiatric conditions. RESULTS: Among older adults, prevalence of lifetime and
      past 12-month AUDs were 16.1% and 1.5% and lifetime and past 12-month TUDs were
      8.7% and 4.0%, respectively. Lifetime TUD was associated with increased odds of
      both lifetime (odds ratio [OR]: 4.17; 95% confidence interval [CI]: 3.30-5.26)
      and past 12-month (OR: 2.52; 95% CI: 1.50-4.24) AUDs, and lifetime AUD was
      associated with increased odds of both lifetime (OR: 4.13; 95% CI: 3.28-5.210 and
      past 12-month (OR: 3.51; 95% CI: 2.47-4.96) TUDs. Any lifetime mood, anxiety, or
      personality disorder among older adults was associated with increased odds of
      lifetime AUD and TUD, any lifetime mood disorder was associated with increased
      odds of past 12-month AUD and TUD, and any personality disorder was associated
      with past 12-month TUD. CONCLUSION: There is a strong association between AUD and
      TUD among older U.S. adults as well as associations between AUD and TUD with
      mood, anxiety, and personality disorders. Understanding the psychiatric
      conditions associated with AUDs and TUDs, especially past 12-month use disorders
      involving alcohol or tobacco, will enable healthcare providers to target
      screening and be more aware of symptoms and signs of potential AUDs and TUDs
      among those at higher risk.

PMID- 24021219
TI  - Education modulates the impact of white matter lesions on the risk of mild
      cognitive impairment and dementia.
AB  - OBJECTIVES: Conflicting results have been reported regarding the association
      between white matter lesions (WML) and cognitive impairment. We hypothesized that
      education, a marker of cognitive reserve (CR), could modulate the effects of WML
      on the risk of mild cognitive impairment (MCI) or dementia. METHODS: We followed
      500 healthy subjects from a cohort of community-dwelling persons aged 65 years
      and over (ESPRIT Project). At baseline, WML volume was measured using a semi
      automatic method on T2-weighted MRI. Standardized cognitive and neurological
      evaluations were repeated after 2, 4, and 7 years. The sample was dichotomized
      according to education level into low (<=8 years) and high (>8 years) education
      groups. Cox proportional hazard models were constructed to study the association
      between WML and risk of MCI/dementia. RESULTS: The interaction between education
      level and WML volume reached significance (p = 0.017). After adjustment for
      potential confounders, the association between severe WML and increased
      MCI/dementia risk was significant in the low education group (<=8 years) (p =
      0.02, hazard ratio [HR]: 3.77 [1.29-10.99]), but not in the high education group
      (>8 years) (p = 0.82, HR: 1.07 [0.61-1.87]). CONCLUSIONS: Severe WML
      significantly increases the risk of developing MCI/dementia over a 7-year period
      in low educated participants. Subjects with higher education levels were seen to
      be more likely to be resilient to the deleterious effects of severe WML. The CR
      hypothesis suggests several avenues for dementia prevention.

PMID- 24021221
TI  - Self- or physician-reported diabetes, glycemia markers, and cognitive functioning
      in older adults in Germany.
AB  - OBJECTIVES: To assess the association of different diabetes-related variables,
      including self- and physician-reported information, as well as biomarkers, with
      cognitive functioning in the elderly general population in Germany. DESIGN: Cross
      sectional observational study. SETTING AND PARTICIPANTS: A total of 1,697
      subjects with a mean +/- standard deviation age of 74 +/- 2.8 years were
      included. These were recruited from among the participants of an ongoing
      epidemiological study of the elderly general population in Saarland state and had
      been recruited 5 years earlier on the occasion of a health screening exam by
      their general practitioners. MEASUREMENTS: Cognitive functioning across six
      subdomains was assessed using the Cognitive Telephone Screening Instrument. Data
      on prevalent diabetes at baseline were obtained from the study participants and
      their general practitioners. Baseline fasting glucose was assessed as part of the
      screening exam, and baseline HbA1c was determined centrally by standardized
      methods. RESULTS: The association of cognitive functioning with self-reported
      diabetes (N = 189) was more pronounced than with physician-reported diabetes (N =
      280). HbA1c showed a nonlinear association with cognitive functioning, with a
      peak of cognitive performance in the central quintile of HbA1c. In the case of
      fasting glucose, lower cognitive functioning was only observed in the highest
      quintile. The estimates were robust in confounder-adjusted models, but
      attentuated when excluding subjects with baseline prevalent or follow-up incident
      diabetes. CONCLUSIONS: Future studies of diabetes-related biomarkers and
      cognition should take possible nonlinearity of the relationships into account, as
      the strength of the associations otherwise might be underestimated.

PMID- 24021220
TI  - Neurobiology of delusions, memory, and insight in Alzheimer disease.
AB  - OBJECTIVE: Delusional thoughts are common among patients with Alzheimer disease
      (AD) and may be conceptually linked to memory deficits (cannot recall accurate
      information, which leads to inaccurate beliefs) and poor insight (unable to
      appreciate the illogic of beliefs). This study's goals were to examine the
      clinical associations among delusions, memory deficits, and poor insight; explore
      neurobiologic correlates for these symptoms; and identify shared mechanisms.
      METHODS: In a cross-sectional analysis, 88 outpatients with AD (mean Mini-Mental
      State Exam score: 19.3) were studied. Delusional thoughts were assessed with the
      Neuropsychiatric Inventory, level of inaccurate insight was assessed with the
      Neurobehavioral Rating Scale, and memory was assessed with the Mattis Dementia
      Rating Scale memory subscale. (18)F-fluorodeoxyglucose positron emission
      tomography was used to measure regional cortical metabolism. Relationships
      between clinical ratings and regional cortical metabolic activity (voxel-based)
      were assessed using SPM2. RESULTS: Patients with delusions had lower Dementia
      Rating Scale memory subscale scores. Neurobehavioral Rating Scale inaccurate
      insight scores were no different in those with and without delusions. Cortical
      metabolic activity was lower in the right lateral frontal cortex, orbitofrontal
      cortex, and bilateral temporal cortex in patients with delusions. Low cortical
      metabolic activity in the right lateral, inferior, and medial temporal cortex was
      associated with poorer memory. This region partially overlapped the region of
      hypometabolism associated with delusions. In contrast, low cortical metabolic
      activity in bilateral medial frontal cortex was associated with poor insight.
      CONCLUSION: Delusions in AD are associated with dysfunction in specific frontal
      and temporal cortical regions. Delusions are partially clinically and
      neurobiologically linked to memory deficits but not to poor insight.

PMID- 24021223
TI  - Psychosocial and reincarceration risks among older adults in mental health
      courts.
AB  - OBJECTIVE: Older adults are increasingly involved in the criminal justice system,
      yet there is limited research regarding their needs and experiences. This study
      examined differences in psychosocial experiences and reincarceration between
      older and younger adults with psychiatric disorders involved in the criminal
      justice system. METHODS: Participants (N = 80) were recruited from two mental
      health courts in the midwestern United States. Bivariate analyses examined age
      related differences in psychosocial experiences and reincarceration between
      younger and older participants. RESULTS: Older adults, on average, experienced
      more treatment adherence and fewer probation violations than younger adults
      during the 6-month follow-up; however, they experienced comparable risk for
      reincarceration. Older adults' substance use, service use, housing instability,
      and program retention were similar to their younger counterparts. CONCLUSION:
      Despite older mental health court participants' treatment adherence and reduced
      probation violations, they are at risk for incarceration, substance use, and
      housing instability.

PMID- 24021222
TI  - Relative effectiveness of reappraisal and distraction in regulating emotion in
      late-life depression.
AB  - OBJECTIVES: The present study compares the effectiveness of two strategies,
      reappraisal and distraction, in reducing negative affect in older adults induced
      by focusing on personally relevant negative events and stressors. PARTICIPANTS:
      30 adults with major depressive disorger (MDD) and 40 never-depressed (ND)
      comparison participants ages 60 years and over (mean age = 69.7 years). DESIGN
      AND MEASUREMENTS: Participants underwent three affect induction trials, each
      followed by a different emotion regulation strategy: distraction, reappraisal,
      and a no-instruction control condition. Self-reported affect was recorded pre-
      and post-affect induction, and at one-minute intervals during regulation.
      RESULTS: Across groups, participants reported greater reductions in negative
      affect with distraction than reappraisal or the no-instruction control condition.
      An interaction between group and regulation condition indicated that distraction
      was more effective in reducing negative affect in the MDD group than the ND
      group. CONCLUSIONS: These results suggest that distraction is an especially
      effective strategy for reducing negative affect in older adults with MDD. Finding
      ways to incorporate distraction skills into psychotherapeutic interventions for
      late-life MDD may improve their effectiveness, especially for short-term
      improvement of affect following rumination.

PMID- 24021224
TI  - Characteristics of auditory hallucinations and associated factors in older adults
      with schizophrenia.
AB  - OBJECTIVE: To examine the characteristics of auditory verbal hallucinations and
      associated factors in older adults with schizophrenia. METHODS: One hundred
      ninety-eight persons aged 55 and older living in the community who had developed
      schizophrenia before age 45 years were assessed for the presence, topography,
      content, and subjective qualities of auditory hallucinations. George's social
      antecedent model of psychopathology was used to examine 17 predictor variables of
      auditory hallucinations. RESULTS: Thirty-two percent experienced auditory verbal
      hallucinations. More than half heard voices daily, heard good/pleasant voices, or
      had command hallucinations; 25% obeyed "bad" voices, whereas 87% obeyed "good"
      voices. There were no significant differences in depression and social
      functioning between persons judging their voices to be good versus bad. In
      logistic regression analysis, depressive symptoms, Positive and Negative Syndrome
      Scale delusion score (>2), and male gender were associated with auditory verbal
      hallucinations. CONCLUSION: Older adults with schizophrenia had a lower rate of
      auditory verbal hallucinations than had been reported previously for younger
      persons with schizophrenia. For most features of auditory verbal hallucinations,
      older adults had similar rates to younger persons. However, older adults were
      more apt to judge their voices as good and more likely to obey the good voices
      than those voices perceived as bad. From a clinical standpoint, this may be
      construed as a potentially useful coping strategy. However, subjective judgments
      about voices did not significantly affect mood or functioning, and the presence
      of auditory verbal hallucinations was associated with more depressive symptoms.

PMID- 24021226
TI  - Complex 3D blood flow pathways in two cases of aorta to right heart fistulae: a
      4D flow MRI study.
AB  - We present an analysis of 3D blood flow in two cases of Sinus of Valsalva to
      right heart fistulae based on 4D flow MRI. Despite similar underlying pathology,
      3D visualization revealed intricate differences in flow patterns connecting the
      systemic and pulmonary circulation. The cases illustrates the potential of 4D
      flow MRI to complement the evaluation of complex structural heart disease by
      assessing complex flow dynamics and providing quantitative information of flow
      ratios and flow rates. 

PMID- 24021225
TI  - Depressive symptoms in Chinese-American subjects with cognitive impairment.
AB  - OBJECTIVES: To compare the prevalence of depressive symptoms and frequency of
      antidepressant use between a group of elderly Chinese-American subjects with and
      without cognitive impairment and a group of matched white subjects. A secondary
      aim was to examine the clinical and demographic predictors of depressive symptoms
      across these groups. METHODS: The study was conducted at an academic neurology
      subspecialty clinic. This was a case-control study with 140 Chinese-American
      subjects and 140 demographically and cognitively matched white subjects. In each
      group, there were 48 cognitively normal and 92 cognitively impaired participants
      (49 with mild cognitive impairment, 43 with Alzheimer disease). The proportion of
      individuals with significant depressive symptoms, as indicated by a Geriatric
      Depression Scale score >=6 of 15, and frequency of antidepressant use were
      compared across groups by using chi(2) analysis. Factors predicting depressive
      symptoms, including racial and diagnostic group, age, gender, Mini-Mental State
      Examination score, level of functional impairment, education level, and medical
      comorbidities, were assessed by using linear regression analysis. RESULTS:
      Significant depressive symptoms were more common in cognitively impaired Chinese
      American (35%) than cognitively impaired white (15%; chi(2)[1] = 9.4; p = 0.004)
      subjects. Chinese-American subjects with cognitive impairment were less likely to
      be receiving treatment for depression (12%) than white subjects with cognitive
      impairment (37%; chi(2)[1] = 15.6; p = 0.002). Racial and diagnostic group, age,
      level of functional impairment, Mini-Mental State Examination score, and
      education level were all statistically significant independent predictors of
      Geriatric Depression Scale score. CONCLUSIONS: Elderly Chinese-American subjects
      with cognitive impairment are at increased risk for unrecognized and untreated
      depressive symptoms compared with elderly white subjects with cognitive
      impairment. Education level may contribute to this risk or it may be a surrogate
      marker for other factors contributing to depressive symptoms in this group.

PMID- 24021227
TI  - Systems approaches to studying the immune response in tuberculosis.
AB  - Tuberculosis (TB) remains a disease of considerable mortality and morbidity.
      Studies employing microarrays to derive transcriptional profiles of the host
      response during TB, which combined with data from experimental systems have
      highlighted a potentially detrimental role for type I interferons during
      infection, with important implications for vaccine and therapeutic development.
      In addition, these studies have provided candidate biomarkers which may advance
      diagnosis and treatment monitoring. These studies thus exemplify the promise of a
      systems biology approach to study complex infectious disease such as TB. 

PMID- 24021228
TI  - Four-arm PEG cross-linked hyaluronic acid hydrogels containing PEGylated
      apoptotic TRAIL protein for treating pancreatic cancer.
AB  - Four-arm polyethylene glycol (PEG) cross-linked hyaluronic acid (HA) hydrogels
      containing PEGylated tumor necrosis factor-related apoptosis-inducing ligand (PEG
      TRAIL) were fabricated, and their antitumor effects were evaluated in pancreatic
      cell (Mia Paca-2)-xenografted mice. HA was conjugated with 4-arm PEG(10k)-amine
      (a cross-linker) at ratios of 100:1 and 100:2 using 1-ethyl-3-(3
      dimethylaminopropyl)-carbodiimide hydrochloride as a cross-linker, and TRAIL or
      PEG-TRAIL was incorporated into these HA hydrogels. HA hydrogels at a 100:1 ratio
      were prepared in good yields (>88%), were moderately stiff, and gradually
      released PEG-TRAIL over ~14 days in vitro and over ~7 days in vivo (as determined
      by high-pressure liquid chromatography and infrared imaging). The released PEG
      TRAIL was found to have obvious apoptotic activity in Mia Paca-2 cells. PEG-TRAIL
      HA hydrogels displayed remarkably more antitumor efficacy than TRAIL HA hydrogels
      in Mia Paca-2 cell-xenografted mice in terms of tumor volumes (size) and weights
      (453.2mm(3) and 1.03 g vs. 867.5mm(3) and 1.86 g). Furthermore, this improved
      antitumor efficacy was found to be due to the apoptotic activity of PEG-TRAIL in
      vivo (determined by a TUNEL assay) despite its substantially lower cytotoxicity
      than native TRAIL (IC50 values: 71.8 and 202.5 ng ml(-1), respectively). This
      overall enhanced antitumor effect of PEG-TRAIL HA hydrogels appeared to be due to
      the increased stability of PEGylated TRAIL in HA hydrogels. These findings
      indicate that this HA hydrogel system combined with PEG-TRAIL should be
      considered a potential candidate for the treatment of pancreatic cancer.

PMID- 24021229
TI  - Non-invasive pH determination adjacent to degradable biomaterials in vivo.
AB  - An appropriate pH level is an important prerequisite for the physiologal
      functioning of cells and tissues. Changes in the extracellular pH often lead to
      specific cellular reactions and an altered metabolism of cells and tissues
      influences the extracellular pH range. Thus a method to monitor the extracellular
      pH is a valuable tool to track specific tissue reactions. In this article we
      describe a method for the determination of the pH range adjacent to degradable
      biomaterials using wireless in vivo imaging. Using hairless but immunocompetent
      mice the fluorophor 5-(6)-carboxy SNARF-1 and the in vivo fluorescence and
      multispectral acquisition and analysis system Maestro it is possible to track
      shifts in pH in small living animals over a longer period of time. This method is
      especially suitable for studies which focus on the interaction of degrading
      biomaterials with their adjacent tissues. 

PMID- 24021230
TI  - Design of imperfectly amphipathic alpha-helical antimicrobial peptides with
      enhanced cell selectivity.
AB  - Antimicrobial peptides (AMPs), which are produced by multicellular organisms as a
      defense mechanism against competing pathogenic microbes, appear to be excellent
      candidates for the development of novel antimicrobial agents. Amphipathicity is
      traditionally believed to be crucial to the de novo design or systematic
      optimization of AMPs. In this study, we designed a series of short alpha-helical
      AMPs with imperfect amphipathicity to augment the arsenal of strategies and to
      gain further insights into their antimicrobial and hemolytic activity. These
      imperfectly amphipathic alpha-helical AMPs were designed by replacing the paired
      charged amino acid residues on the polar face of an amphipathic peptide with
      tryptophan residues on the basis of alpha-helical protein folding principles.
      PRW4, an imperfectly amphipathic alpha-helical AMP with hydrogen bonds formed by
      paired tryptophan residues, was observed to be more selective towards bacterial
      cells than toward human red blood cells. PRW4 was also effective against Gram
      negative and Gram-positive bacteria, and fluorescence spectroscopy, flow
      cytometry, scanning electron microscopy and transmission electron microscopy
      indicated that PRW4 killed microbial cells by permeabilizing the cell membrane
      and damaging their membrane integrity. Therefore, disruptive amphipathicity has
      excellent potential for the rational design and optimization of AMPs with
      promising antimicrobial activities. 

PMID- 24021231
TI  - Visible light cured thiol-vinyl hydrogels with tunable degradation for 3D cell
      culture.
AB  - We report here a synthetically simple yet highly tunable and diverse visible
      light mediated thiol-vinyl gelation system for fabricating cell-instructive
      hydrogels. Gelation was achieved via a mixed-mode step-and-chain-growth
      photopolymerization using functionalized 4-arm poly(ethylene glycol) as backbone
      macromer, eosin-Y as photosensitizer, and di-thiol containing molecule as dual
      purpose co-initiator/cross-linker. N-vinylpyrrolidone (NVP) was used to
      accelerate gelation kinetics and to adjust the stiffness of the hydrogels.
      Visible light (wavelength: 400-700 nm) was used to initiate rapid gelation (gel
      points: ~20s) that reached completion within a few minutes. The major differences
      between current thiol-vinyl gelation and prior visible light mediated
      photopolymerization are that: (1) the co-initiator triethanolamine (TEA) used in
      the previous systems was replaced with multifunctional thiols and (2) mixed-mode
      polymerized gels contain less network heterogeneity. The gelation kinetics and
      gel properties at the same PEG macromer concentration could be tuned by changing
      the identity of vinyl groups and di-thiol cross-linkers, as well as concentration
      of cross-linker and NVP. Specifically, acrylate-modified PEG afforded the fastest
      gelation rate, followed by acrylamide and methacrylate-functionalized PEG.
      Increasing NVP concentration also accelerated gelation and led to a higher
      network cross-linking density. Further, increasing di-thiol peptide concentration
      in the gel formulation increased hydrogel swelling and decreased gel stiffness.
      Due to the formation of thiol-ether-ester bonds following thiol-acrylate
      reaction, the gels degraded hydrolytically following a pseudo first order
      degradation kinetics. Degradation rate was controlled by adjusting thiol or NVP
      content in the polymer precursor solution. The cytocompatibility and utility of
      this hydrogel system were evaluated using in situ encapsulation of human
      mesenchymal stem cells (hMSC). Encapsulated hMSCs remained alive (>90%)
      throughout the duration of the study and the cells were differentiated down
      osteogenic lineage with varying degrees by controlling the rate and mode of gel
      degradation.

PMID- 24021233
TI  - Surgical aortic valve replacement in very elderly patients aged 80 years and
      over: evaluation of early clinical outcomes.
AB  - BACKGROUND: An increasing number of very elderly patients aged >=80 years will
      require aortic valve replacement (AVR) for severe aortic stenosis (AS). Many are
      classified as high-risk surgical candidates. Transcatheter aortic valve
      implantation (TAVI) has been proposed as an alternative to surgical AVR (SAVR)
      for high-risk patients. We evaluated early clinical outcomes of very elderly
      patients undergoing SAVR to optimise TAVI candidate selection. METHODS: We
      conducted a retrospective case review of 132 consecutive patients aged >=80 years
      undergoing isolated SAVR (49 patients) or combined SAVR/CABG (83 patients) during
      February 2002-January 2010 at a single tertiary referral hospital. Risk for
      cardiac surgery was calculated using the logistic EuroSCORE (ES(log)). Mortality
      and morbidity data were collected for the 30-day postoperative period. RESULTS:
      Thirty-day mortality rate was 8.3% for patients undergoing SAVR (6.1% for
      isolated SAVR and 9.6% for SAVR/CABG). Permanent stroke occurred in 3.8% and
      renal insufficiency in 7.6% of the cohort. Thirty-five percent of patients had
      left ventricular ejection fraction <50%, 67% had advanced symptoms (NYHA class
      III or IV), and 42% of patients were stratified as high-risk (ES(log)>=20%).
      CONCLUSIONS: SAVR can be performed in very elderly patients with acceptable
      operative morbidity and mortality. The outcomes at our institution are comparable
      to contemporary SAVR and TAVI outcomes.

PMID- 24021234
TI  - New CoreValve Evolut 23 mm technology for treatment of degenerated bioprosthesis.
AB  - The treatment of degenerated surgical bio-prosthetic heart valves (BHV) has been
      reported as a novel indication for TAVI. The intervention may be complicated by
      high residual transvalvular gradients and coronary ostia obstruction, especially
      in small size BHV. We report two cases of BHVs treated with the new CoreValve
      Evolut 23 mm highlighting the importance of fluoroscopic guidance, based on BHV
      markers, in achieving a correct TAVI implantation. The small dimensions of the
      new CoreValve Evolut 23 allowed us to obtain low residual gradients even in this
      particular subset of degenerated BHV.

PMID- 24021235
TI  - E-VITA Jotec open hybrid stent graft system for the treatment of complex thoracic
      aortic aneurysm and dissection--a four year experience.
AB  - INTRODUCTION: The management of complex aortic aneurysms and dissections
      involving both the aortic arch and descending aorta include operations associated
      with significant risks of mortality and morbidity. The advent of hybrid systems
      such as the E-VITA Jotec open hybrid stent graft system (E-VITA) provides the
      advantage of single stage repair with follow up repair of any remaining
      downstream aneurysm and dissection being easier to manage. METHODS: Herein we
      report a series of seven cases utilising E-VITA over a four year period. RESULTS:
      The average patient age was 66.9 years of age (range: 55-78 years). The average
      cardiopulmonary bypass and circulatory arrest times were 237.14 min and 47.83
      min. There was one operative mortality. Follow up as far as three years revealed
      good results with few complications. CONCLUSION: The E-VITA is a feasible
      management option in the treatment of complex aortic aneurismal disease and
      dissections. It allows treatment of patients that may have previously not been
      considered suitable for two-stage surgical procedure.

PMID- 24021232
TI  - Incorporation of heparin into biomaterials.
AB  - This review provides an overview of the incorporation of heparin into
      biomaterials with a focus on drug delivery and the use of heparin-based
      biomaterials for self-assembly of polymer networks. Heparin conjugation to
      biomaterials was originally explored to reduce the thrombogenicity of materials
      in contact with blood. Many of the conjugation strategies that were developed for
      these applications are still popular today for other applications. More recently
      heparin has been conjugated to biomaterials for drug delivery applications. Many
      of the delivery approaches have taken advantage of the ability of heparin to bind
      to a wide variety of growth factors, protecting them from degradation and
      potentiating interactions with cell surface receptors. More recently, the use of
      heparin as a base polymer for scaffold fabrication has also been explored, often
      utilizing non-covalent binding of heparin with peptides or proteins to promote
      self-assembly of hydrogel networks. This review will highlight recent advances in
      each of these areas. 

PMID- 24021236
TI  - Lung function abnormalities are highly frequent in patients with heart failure
      and preserved ejection fraction.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFPEF) is the most
      prevalent form of heart failure in outpatients. Yet, the pathophysiology of this
      syndrome is unclear and pharmacological treatment does not improve prognosis.
      Because breathlessness during activities of daily living is the most frequent
      complaint of patients with HFPEF, we hypothesised that lung function may be often
      abnormal in these patients due to either a direct effect of HFPEF and/or shared
      risk factors. In this study we explore the frequency, type and severity of lung
      function abnormalities in HFPEF. METHODS: We measured forced spirometry, static
      lung volumes, pulmonary diffusing capacity (DL(CO)) and arterial blood gases in
      69 outpatients with newly diagnosed symptomatic HFPEF. RESULTS: We found that 94%
      of the patients showed abnormalities in at least one of the lung function
      measurements obtained: spirometry was abnormal in 59%, DL(CO) in 83% and arterial
      hypoxaemia was present in 62%. Their severity varied between patients, they were
      more prevalent in patients with NYHA functional class III/IV, and most often they
      were undiagnosed and untreated. CONCLUSIONS: Lung function abnormalities are very
      frequent in HFPEF patients. A greater awareness among clinicians may contribute
      to improve their management and health status.

PMID- 24021238
TI  - Dystrophin complex functions as a scaffold for signalling proteins.
AB  - Dystrophin is a 427kDa sub-membrane cytoskeletal protein, associated with the
      inner surface membrane and incorporated in a large macromolecular complex of
      proteins, the dystrophin-associated protein complex (DAPC). In addition to
      dystrophin the DAPC is composed of dystroglycans, sarcoglycans, sarcospan,
      dystrobrevins and syntrophin. This complex is thought to play a structural role
      in ensuring membrane stability and force transduction during muscle contraction.
      The multiple binding sites and domains present in the DAPC confer the scaffold of
      various signalling and channel proteins, which may implicate the DAPC in
      regulation of signalling processes. The DAPC is thought for instance to anchor a
      variety of signalling molecules near their sites of action. The dystroglycan
      complex may participate in the transduction of extracellular-mediated signals to
      the muscle cytoskeleton, and beta-dystroglycan was shown to be involved in MAPK
      and Rac1 small GTPase signalling. More generally, dystroglycan is view as a cell
      surface receptor for extracellular matrix proteins. The adaptor proteins
      syntrophin contribute to recruit and regulate various signalling proteins such as
      ion channels, into a macromolecular complex. Although dystrophin and dystroglycan
      can be directly involved in signalling pathways, syntrophins play a central role
      in organizing signalplex anchored to the dystrophin scaffold. The dystrophin
      associated complex, can bind up to four syntrophin through binding domains of
      dystrophin and dystrobrevin, allowing the scaffold of multiple signalling
      proteins in close proximity. Multiple interactions mediated by PH and PDZ domains
      of syntrophin also contribute to build a complete signalplex which may include
      ion channels, such as voltage-gated sodium channels or TRPC cation channels,
      together with, trimeric G protein, G protein-coupled receptor, plasma membrane
      calcium pump, and NOS, to enable efficient and regulated signal transduction and
      ion transport. This article is part of a Special Issue entitled: Reciprocal
      influences between cell cytoskeleton and membrane channels, receptors and
      transporters. Guest Editor: Jean Claude Herve. 

PMID- 24021237
TI  - Conformational changes of the bacterial type I ATP-binding cassette importer
      HisQMP2 at distinct steps of the catalytic cycle.
AB  - Prokaryotic solute binding protein-dependent ATP-binding cassette import systems
      are divided into type I and type II and mechanistic differences in the transport
      process going along with this classification are under intensive investigation.
      Little is known about the conformational dynamics during the catalytic cycle
      especially concerning the transmembrane domains. The type I transporter for
      positively charged amino acids from Salmonella enterica serovar Typhimurium (LAO
      HisQMP2) was studied by limited proteolysis in detergent solution in the absence
      and presence of co-factors including ATP, ADP, LAO/arginine, and Mg(2+) ions.
      Stable peptide fragments could be obtained and differentially susceptible
      cleavage sites were determined by mass spectrometry as Lys-258 in the nucleotide
      binding subunit, HisP, and Arg-217/Arg-218 in the transmembrane subunit, HisQ. In
      contrast, transmembrane subunit HisM was gradually degraded but no stable
      fragment could be detected. HisP and HisQ were equally resistant under pre- and
      post-hydrolysis conditions in the presence of arginine-loaded solute-binding
      protein LAO and ATP/ADP. Some protection was also observed with LAO/arginine
      alone, thus reflecting binding to the transporter in the apo-state and
      transmembrane signaling. Comparable digestion patterns were obtained with the
      transporter reconstituted into proteoliposomes and nanodiscs. Fluorescence
      lifetime spectroscopy confirmed the change of HisQ(R218) to a more apolar
      microenvironment upon ATP binding and hydrolysis. Limited proteolysis was
      subsequently used as a tool to study the consequences of mutations on the
      transport cycle. Together, our data suggest similar conformational changes during
      the transport cycle as described for the maltose ABC transporter of Escherichia
      coli, despite distinct structural differences between both systems. 

PMID- 24021239
TI  - Role of Saccharomyces cerevisiae Trk1 in stabilization of intracellular potassium
      content upon changes in external potassium levels.
AB  - Saccharomyces cerevisiae cells are able to grow at very different potassium
      concentrations adapting its intracellular cation levels to changes in the
      external milieu. Potassium homeostasis in wild type cells resuspended in media
      with low potassium is an example of non-perfect adaptation since the same
      intracellular concentration is not approached irrespective of the extracellular
      levels of the cation. By using yeasts lacking the Trk1,2 system or expressing
      different versions of the mutated main plasma membrane potassium transporter
      (Trk1), we show that Trk1 is not essential for adaptation to potassium changes
      but the dynamics of potassium loss is very different in the wild type and in
      trk1,2 mutant or in yeasts expressing Trk1 versions with highly impaired
      transport characteristics. We also show that the pattern here described can be
      also fulfilled by heterologous expression of NcHAK1, a potassium transporter not
      belonging to the TRK family. Hyperpolarization and cationic drugs sensitivity in
      mutants with defective transport capacity provide additional support to the
      hypothesis of connections between the activity of the Trk system and the plasma
      membrane H(+) ATPase (Pma1) in the adaptive process. 

PMID- 24021241
TI  - Persistent gene expression changes in NAc, mPFC, and OFC associated with previous
      nicotine or amphetamine exposure.
AB  - Highly addictive drugs like nicotine and amphetamine not only change an
      individual's behaviour in the short and long-term, they also induce persistent
      changes in neuronal excitability and morphology. Although research has started to
      examine the epigenetic changes that occur immediately after drug exposure, there
      has been little investigation into the persistent modifications to the epigenome
      that likely moderate the stable maintenance of the neurological changes. Male
      Long-Evans rats were administered amphetamine, nicotine, or saline for 14
      consecutive days, given a 14 day withdrawal period, and then sacrificed. DNA from
      the mPFC, OFC, and nucleus accumbens (NAc) was used for global DNA methylation
      analysis and RNA from the same brain regions was used for gene expression
      analysis. Following the two-week withdrawal period, exposure to amphetamine or
      nicotine was associated with a decrease in global DNA methylation in each brain
      region examined. Previous exposure to nicotine was associated with changes in
      expression of 16 genes (NAc:6, mPFC:5, OFC:5) whereas exposure to amphetamine was
      associated with changes in expression of 25 genes (NAc:13, OFC:8, mPFC:4). The
      persistent epigenetic changes associated with exposure to amphetamine and
      nicotine were region and drug dependent, and differ from the latent epigenetic
      changes that occur immediately after drug exposure. The changes in DNA
      methylation are consistent with the gene expression results and provide further
      support to the notion that DNA methylation is the key regulatory mechanism for
      experience dependent changes. 

PMID- 24021242
TI  - Improved circuit model of open-ended coaxial probe for measurement of the
      biological tissue dielectric properties between megahertz and gigahertz.
AB  - This note describes an improved equivalent circuit analysis model for open-ended
      coaxial probes for measurement of the dielectric properties of biological tissues
      below the gigahertz level. Some parameters in the conventional model that
      influence the measurement results were found to be still relative to the
      dielectric properties of the test sample and the terminal admittance of the probe
      was found to be dependent on the frequency. This was not found to be the case
      with the conventional model. According to the simulation results in frequency
      range from 30 MHz to 1 GHz, a polynomial expression was found to fit the
      frequency-admittance curve for terminal admittance and the equivalent circuit
      expression of probe terminal admittance was finally modified. The simulated
      annealing algorithm was used to calculate the dielectric properties of the new
      expression. The accuracy of the improved model was validated through a simulation
      test and experiment based on a series of solutions over 30 MHz-1 GHz. The new
      model was compared to the conventional model and was found to provide more
      accurate permittivity estimation over a wider frequency range than the
      conventional model if said range was between megahertz and gigahertz. 

PMID- 24021243
TI  - Selenium supplementation and autoimmune thyroid diseases.

PMID- 24021244
TI  - Discriminant analysis between malignant mesothelioma and reactive mesothelium
      using nuclear three-dimensional analysis is useful for morphologically suspicious
      cases.
AB  - OBJECTIVE: Morphological discrimination between malignant mesothelioma (MM) and
      reactive mesothelium (RM) is often difficult. Stereological analysis of nuclear
      luminance using centrifuged smear samples from coelomic fluid and discriminant
      analysis based on Mahalanobis distance may help to more accurately discriminate
      between MM and RM. In the present study, discriminant analysis was conducted on
      cytological specimens using the auto-smear method in a blinded manner with regard
      to histological results. STUDY DESIGN: Coelomic fluid samples of 28 cases,
      cytologically diagnosed using the auto-smear method, were analyzed to determine
      pixel counts, the number of focus layers, 3-dimensional variation in the
      coefficient of variation of nuclear luminance between the focus layers as well as
      roundness in about 30-50 atypical cell nuclei per case. These measurements were
      employed to determine malignancy based on Mahalanobis distance. RESULTS:
      Discrimination rates were as high as 91.7% for MM and 82.7% for RM. The
      discrimination rates of MM with histology were >80% in 8 of 10 suspicious cases
      with the initial cytology. CONCLUSION: Our method allowed accurate discrimination
      between MM and RM and provides a useful alternative for the diagnosis of
      suspicious cases where morphological diagnosis of malignancy is difficult.

PMID- 24021245
TI  - Systematic review and meta-analysis of the current evidence on the duration of
      protection by bacillus Calmette-Guerin vaccination against tuberculosis.
AB  - BACKGROUND: Recent evidence suggests that the duration of protection by bacillus
      Calmette-Guerin (BCG) may exceed previous estimates with potential implications
      for estimating clinical and cost-efficacy. OBJECTIVES: To estimate the protection
      and duration of protection provided by BCG vaccination against tuberculosis,
      explore how this protection changes with time since vaccination, and examine the
      reasons behind the variation in protection and the rate of waning of protection.
      DATA SOURCES: Electronic databases including MEDLINE, Excerpta Medica Database
      (EMBASE), Cochrane Databases, NHS Economic Evaluation Database (NHS EED),
      Database of Abstracts of Reviews of Effects (DARE), Web of Knowledge, Biosciences
      Information Service (BIOSIS), Latin American and Caribbean Health Sciences
      Literature (LILACs), MEDCARIB Database, Cumulative Index to Nursing and Allied
      Health Literature (CINAHL) were searched from inception to May 2009. Index to
      Theses, System for Information on Grey Literature in Europe (SIGLE), Centre for
      Agricultural Bioscience International (CABI) Abstracts, Scopus, Article First,
      Academic Complete, Africa-Wide Information, Google Scholar, Global Health,
      British National Bibliography for Report Literature, and clinical trial
      registration websites were searched from inception to October 2009. REVIEW
      METHODS: Electronic databases searches, screening of identified studies, data
      extraction and analysis were undertaken. Meta-analysis was used to present
      numerical and graphical summaries of clinical efficacy and efficacy by time since
      vaccination. Evidence of heterogeneity was assessed using the tau-squared
      statistic. Meta-regression allowed the investigation of observed heterogeneity.
      Factors investigated included BCG strain, latitude, stringency of pre-BCG
      vaccination tuberculin testing, age at vaccination, site of disease, study design
      and vulnerability to biases. Rate of waning of protection was estimated using the
      ratio of the measure of efficacy after 10 years compared with the efficacy in the
      first 10 years of a study. RESULTS: Study selection. A total of 21,030 references
      were identified, providing data on 132 studies after abstract and full-text
      review. Efficacy. Protection against pulmonary tuberculosis in adults is
      variable, ranging from substantial protection in the UK MRC trial {rate ratio
      0.22 [95% confidence interval (CI) 0.16 to 0.31]}, to absence of clinically
      important benefit, as in the large Chingleput trial [rate ratio 1.05 (95% CI 0.88
      to 1.25)] and greater in latitudes further away from the equator. BCG vaccination
      efficacy was usually high, and varied little by form of disease (with higher
      protection against meningeal and miliary tuberculosis) or study design when BCG
      vaccination was given only to infants or to children after strict screening for
      tuberculin sensitivity. High levels of protection against death were observed
      from both trials and observational studies. The observed protective effect of BCG
      vaccination did not differ by the strain of BCG vaccine used in trials. DURATION:
      Reviewed studies showed that BCG vaccination protects against pulmonary and
      extrapulmonary tuberculosis for up to 10 years. Most studies either did not
      follow up participants for long enough or had very few cases after 15 years. This
      should not be taken to indicate an absence of effect: five studies (one trial and
      four observational studies) provided evidence of measurable protection at least
      15 years after vaccination. Efficacy declined with time. The rate of decline was
      variable, with faster decline in latitudes further from the equator and in
      situations where BCG vaccination was given to tuberculin-sensitive participants
      after stringent tuberculin testing. LIMITATIONS: The main limitation of this
      review relates to quality of included trials, most of which were conducted before
      current standards for reporting were formulated. In addition, data were lacking
      in some areas and the review had to rely on evidence from observational studies.
      CONCLUSIONS: BCG vaccination protection against tuberculosis varies between
      populations, to an extent that cannot be attributed to chance alone. Failure to
      exclude those already sensitised to mycobacteria and study latitude closer to the
      equator were associated with lower efficacy. These factors explained most of the
      observed variation. There is good evidence that BCG vaccination protection
      declines with time and that protection can last for up to 10 years. Data on
      protection beyond 15 years are limited; however, a small number of trials and
      observational studies suggest that BCG vaccination may protect for longer.
      Further studies are required to investigate the duration of protection by BCG
      vaccination. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 24021246
TI  - Efficacy and safety of tocilizumab combined with cyclosporine A in a patient with
      rheumatoid arthritis and concomitant chronic hepatitis C virus infection.

PMID- 24021247
TI  - Racial and socioeconomic disparities in sexual activity among older married
      Malaysians.
AB  - Sexuality as an important part of life has not been well studied in Malaysia,
      particularly among older adults. The main aim of this study was to investigate
      the racial and socioeconomic differences in sexual activity among older married
      Malaysians. Data for this study consisting of 1036 older married adults aged 60
      years and older were obtained from the nationwide community-based cross-sectional
      survey entitled "Determinants of Wellness among Older Malaysian: A Health
      Promotion Perspective", conducted in 2010. Data were analyzed using SPSS version
      21 for Windows. The results showed that 57.3% (95% CI: 54.3-60.3) of the
      respondents (61.6% of men and 50.6% of women) had engaged in sexual intercourse
      during the last 12 months. The adjusted multivariate logistic regression analysis
      revealed that ethnicity and educational attainment were independently and
      significantly associated with sexual activity, after controlling for the possible
      confounding effects of chronic medical conditions and demographic
      characteristics. The findings from this study do support the notion that
      sexuality is a lifelong need and cultural teachings and formal education may have
      important role in maintaining the quality of sexuality in later life. 

PMID- 24021248
TI  - Engineering bone grafts with enhanced bone marrow and native scaffolds.
AB  - The translation of tissue engineering approaches to the clinic has been hampered
      by the inability to find suitable multipotent cell sources requiring minimal in
      vitro expansion. Enhanced bone marrow (eBM), which is obtained by reaming long
      bone medullary canals and isolating the solid marrow putty, has large quantities
      of stem cells and demonstrates significant potential to regenerate bone tissues.
      eBM, however, cannot impart immediate load-bearing mechanical integrity or
      maintain the gross anatomical structure to guide bone healing. Yet, its putty
      like consistency creates a challenge for obtaining the uniform seeding necessary
      to effectively combine it with porous scaffolds. In this study, we examined the
      potential for combining eBM with mechanically strong, osteoinductive trabecular
      bone scaffolds for bone regeneration by creating channels into scaffolds for
      seeding the eBM. eBM was extracted from the femurs of adult Yorkshire pigs using
      a Synthes reamer-irrigator-aspirator device, analyzed histologically, and
      digested to extract cells and characterize their differentiation potential. To
      evaluate bone tissue formation, eBM was seeded into the channels in collagen
      coated or noncoated scaffolds, cultured in osteogenic conditions for 4 weeks,
      harvested and assessed for tissue distribution and bone formation. Our data
      demonstrates that eBM is a heterogenous tissue containing multipotent cell
      populations. Furthermore, coating scaffolds with a collagen hydrogel
      significantly enhanced cellular migration, promoted uniform tissue development
      and increased bone mineral deposition. These findings suggest the potential for
      generating customized autologous bone grafts for treating critical-sized bone
      defects by combining a readily available eBM cell source with decellularized
      trabecular bone scaffolds.

PMID- 24021249
TI  - Is there any association between imidapril hydrochloride stability profile under
      dry air conditions and cancer initiation?
AB  - Stability study for imidapril hydrochloride (IMD) was performed under stress
      conditions of increased temperature (T=373 K) and decreased relative air humidity
      (RH=0%) in order to obtain and identify its degradation product. The degradation
      sample stored for 15 days under the above environmental conditions was analyzed
      by LC-MS technique and it was found that the only degradation impurity formed in
      the course of the investigated drug degradation was IMD diketopiperazine
      derivative (DKP) which was produced by dehydration and intramolecular
      cyclization. The kinetics of its formation was analyzed by a revalidated RP-HPLC
      method and the kinetic model of this reaction was established. It was concluded
      that the DKP formation follows Prout-Tompkins kinetics with the rate constant k+/
      Deltak=2.034+/-0.157*10(-6) [s(-1)]. The obtained degradation impurity was
      further assessed with respect to its mutagenic potential using commercial Ames
      MPF 98/100 microplate format mutagenicity assay kit equipped with Salmonella
      typhimurium strains TA 98 and TA 100. Both strains were exposed to six
      concentrations (in a range of 0.16-5.0mg/mL) of DKP in the presence and absence
      of metabolic activation system. No mutagenic effect was observed confirming that
      the presence of DKP in IMD final dosage form has no impact on cancer initiation.

PMID- 24021250
TI  - Controversies regarding mammography, breast self-examination, and clinical breast
      examination.
AB  - The number of women diagnosed with breast cancer continues to increase, but
      mortality rates have substantially declined. Much of the credit for this decline
      has been attributed to early detection from mammographic screening. However,
      there are significant controversies about the effectiveness of all screening
      tools for breast cancer, concerns about the potential harm that can result from
      screening, and questions about the appropriateness of screening recommendations.
      One of the greatest barriers to achieving consensus is the lack of agreement
      about the purpose of screening efforts. This article reviews many of the current
      controversies and attempts to clarify the arguments. 

PMID- 24021251
TI  - Current breast imaging modalities, advances, and impact on breast care.
AB  - Mammography will continue as the breast cancer screening imaging study of choice
      for the foreseeable future. Ultrasound and magnetic resonance imaging (MRI) are
      widely available adjunctive studies for women with suspicious mammographic or
      clinical findings, and MRI is a screening tool for women with specific increased
      risks for breast cancer. Options for diagnosis will continue to evolve and
      progress. This article discusses a wide variety of imaging options currently used
      and in development, their strengths, limitations, and potential future roles in
      the continuing pursuit of early breast cancer diagnosis, treatment, and follow
      up. 

PMID- 24021252
TI  - Benign breast disorders.
AB  - Full understanding of benign breast disease should enable the obstetrician
      gynecologist to appropriately evaluate symptoms, distinguish between benign and
      malignant processes, determine which benign breast lesions require surgical
      management, and identify patients who are at increased risk of developing breast
      cancer. This article reviews nipple discharge, breast pain, palpable breast
      masses, adolescent breast disorders, inflammatory lesions (including mastitis and
      breast abscesses), and benign breast abnormality detected on imaging and biopsy.
      Each topic provides a review of the clinical presentation, a discussion of the
      appropriate workup, and a further description of specific etiology within each
      category. 

PMID- 24021253
TI  - Hereditary breast/ovarian cancer syndrome: a primer for
      obstetricians/gynecologists.
AB  - An understanding of the diagnosis and clinical management of hereditary breast
      and ovarian cancer syndrome (HBOC) is essential for obstetricians/gynecologists.
      This article provides practical information regarding collecting a family
      history, cancer risk assessment and genetic testing, BRCA-associated cancer
      prognosis and treatment, screening recommendations, and prevention strategies.
      Through appropriate cancer risk assessment, women with BRCA1/2 mutations can be
      identified, and screening and prevention strategies can be used before a
      diagnosis of cancer occurs. Women's health providers with a strong working
      knowledge of HBOC are able to improve the quality of care for women and families
      impacted by BRCA1/2 mutations. 

PMID- 24021254
TI  - Health disparities in breast cancer.
AB  - There has been a growing Black-White disparity in breast cancer mortality after a
      period of relative equivalence. Literature shows that Black Americans with breast
      cancer are less likely to receive optimal care compared with White Americans.
      Tumors in Black Americans are more likely to be poorly differentiated and
      estrogen receptor negative and exhibit a high S-phase fraction compared with
      tumors from White Americans. Differences in dietary habits, breast-feeding, and
      obesity account for some of the population differences in outcome among Black
      Americans. 

PMID- 24021255
TI  - Breast cancer risk assessment, prevention, and the future.
AB  - Today breast cancer remains a major public health problem, although reducing its
      risk is now an achievable medical objective. Risk-assessment models may be used
      in estimating a woman's risk for developing breast cancer and to direct suitable
      candidates for preventive therapy. Researchers are attempting to enhance
      individualized risk assessment through incorporation of phenotypic biomarkers.
      Individual selective estrogen receptor modulators have been approved for breast
      cancer risk reduction, and other drug categories are being studied. It is
      critical that obstetrician-gynecologists be familiar with the evolving science of
      the risk assessment of breast cancer as well as interventional and surveillance
      strategies. 

PMID- 24021256
TI  - Obstetrics and gynecology physicians: a critical part of the health care team for
      women with newly diagnosed breast cancer.
AB  - Most obstetrics and gynecology (OB/GYN) physicians assist their patients at the
      time of a new breast cancer diagnosis. OB/GYN physicians can assure women that
      the tests being performed to map the individual features of the breast cancer
      follow a predictable and organized process. In many cases, it is appropriate to
      confidently reassure the patient of a good outcome based on the diagnostic
      mammography features. Regular attendance at interdisciplinary breast cancer
      conferences will help OB/GYN physicians develop the required knowledge to counsel
      women with newly diagnosed breast cancer. 

PMID- 24021257
TI  - Breast cancer in pregnancy.
AB  - Pregnancy-associated breast cancer is defined as breast cancer diagnosed during
      pregnancy or in the first postpartum year. Breast cancer is one of the more
      common malignancies to occur during pregnancy and, as more women delay
      childbearing, the incidence of breast cancer in pregnancy is expected to
      increase. This article provides an overview of diagnosis, staging, and treatment
      of pregnancy-associated breast cancer. Recommendations for management of breast
      cancer in pregnancy are discussed. 

PMID- 24021258
TI  - Special considerations in early-stage breast cancer patients and survivors.
AB  - Long-term outcomes for early-stage breast cancer have continued to improve, and
      more patients are becoming long-term survivors. In addition to patients' concern
      about risk of developing recurrent disease, they are also concerned about
      potential toxicities of treatment. Current guidelines for long-term follow-up are
      reviewed. Potential toxicities of tamoxifen and aromatase inhibitors are
      reviewed. Management of menopausal symptoms, cancer-related fatigue, and
      cognitive function is discussed. 

PMID- 24021259
TI  - Medicolegal considerations in breast health: the benefits of collaboration
      between OB/GYNs and radiologists.
AB  - A common endeavor shared by physicians practicing in specialty fields of
      Radiology and Obstetrics and Gynecology is the comprehensive care and diagnosis
      of women with breast problems and breast disease. Because each specialty provides
      its respective clinical expertise in breast health, each also shares a concern,
      which is the high risk of litigation associated with a missed or delayed
      diagnosis of breast cancer. This shared concern is well documented for both
      specialties. Instead, it is argued that physicians are better prepared by
      engaging in the practice of evidence-based breast care in their respective
      specialties. 

PMID- 24021260
TI  - Obstetrician-gyenocologists are primary providers for breast health maintenance
      and education.

PMID- 24021261
TI  - Obstetrics and Gynecology Clinics of North America. Breast disorders. Preface.

PMID- 24021262
TI  - Predicting outcomes of acromegaly patients: studies from the Third World.

PMID- 24021263
TI  - TRIM13 regulates caspase-8 ubiquitination, translocation to autophagosomes and
      activation during ER stress induced cell death.
AB  - The emerging evidences suggest that endoplasmic (ER) stress is involved in onset
      of many pathological conditions like cancer and neurodegeneration. The persistent
      ER stress results in misfolded protein aggregates, which are degraded through the
      process of autophagy or lead to cell death through activation of caspases. The
      regulation of crosstalk of autophagy and cell death during ER stress is emerging.
      Ubiquitination plays regulatory role in crosstalk of autophagy and cell death. In
      the current study, we describe the role of TRIM13, RING E3 ubiquitin ligase, in
      regulation of ER stress induced cell death. The expression of TRIM13 sensitizes
      cells to ER stress induced death. TRIM13 induced autophagy is essential for ER
      stress induced caspase activation and cell death. TRIM13 induces K63 linked poly
      ubiquitination of caspase-8, which results in its stabilization and activation
      during ER stress. TRIM13 regulates translocation of caspase-8 to autophagosome
      and its fusion with lysosome during ER stress. This study first time demonstrated
      the role of TRIM13 as novel regulator of caspase-8 activation and cell death
      during ER stress. 

PMID- 24021264
TI  - Mechanical regulation of cancer cell apoptosis and autophagy: roles of bone
      morphogenetic protein receptor, Smad1/5, and p38 MAPK.
AB  - Mechanical forces induced by interstitial fluid flow in and surrounding tissues
      and by blood/lymphatic flow in vessels may modulate cancer cell invasion and
      metastasis and anticancer drug delivery. Our previous study demonstrated that
      laminar flow-induced shear stress induces G2/M arrest in tumor cells. However,
      whether shear stress modulates final cell fate remains unclear. In this study, we
      investigated the role of flow-induced shear stress in modulating the survival of
      four human tumor cell lines, i.e., Hep3B hepatocarcinoma cells, MG63 osteosarcoma
      cells, SCC25 oral squamous carcinoma cells, and A549 carcinomic alveolar basal
      epithelial cells. Laminar shear stress (LSS) ranging from 0.5 to 12dyn/cm(2)
      induced death of these four tumor cell lines. In contrast to LSS at 0.5dyn/cm(2),
      oscillatory shear stress (OSS) at 0.5+/-4dyn/cm(2) cannot induce cancer cell
      death. Both LSS and OSS had no effect on human normal hepatocyte, lung
      epithelial, and endothelial cells. Application of LSS to these four cell lines
      increased the percentage of cells stained positively for annexin V-FITC, with up
      regulations of cleaved caspase-8, -9, and -3, and PARP. In addition, LSS also
      induced Hep3B cell autophagy, as detected by acidic vesicular organelle
      formation, LC3B transformation, and p62/SQSTM1 degradation. By transfecting with
      small interfering RNA, we found that the shear-induced apoptosis and autophagy
      are mediated by bone morphogenetic protein receptor type (BMPR)-IB, BMPR-specific
      Smad1 and Smad5, and p38 mitogen-activated protein kinase in Hep3B cells. Our
      findings provide insights into the molecular mechanisms by which shear stress
      induces apoptosis and autophagy in tumor cells. 

PMID- 24021265
TI  - Anatomic aspects of tibiotalocalcaneal nail arthrodesis.
AB  - During the past 15 years, tibiotalocalcaneal nail arthrodesis has become an
      established procedure for the treatment of specific disorders of the hindfoot and
      ankle. However, controversy exists regarding the proper starting point for
      obtaining and maintaining the correct hindfoot position to allow successful
      fusion. One of the challenges with this procedure is aligning the tibial canal
      with the central talus and calcaneus for placement of the intramedullary nail. We
      performed a cadaver study to evaluate the radiographic and anatomic position of
      the tibial canal and the central talus as it relates to placement of a retrograde
      tibiotalocalcaneal nail. In our subjects, guide wires directed in an antegrade
      fashion down the tibial canal were more likely to enter lateral to the midline of
      the talus and miss the calcaneal body medially. These data have revealed a
      mismatch among the central axis of the tibia, talus, and calcaneus. Surgeons must
      pay careful attention to wire placement across these 3 bone segments during
      retrograde tibiotalocalcaneal nailing. 

PMID- 24021266
TI  - Modification of the Syme amputation to prevent postoperative heel pad migration.
AB  - The Syme amputation (ankle disarticulation level amputation) can be a valuable
      procedure for properly selected patients but might be underused owing to the
      problem of postoperative migration of the heel pad cushion. The present report
      presents a modification of the Syme amputation technique to prevent postoperative
      heel pad migration. The technique was performed in 12 patients, most of whom were
      male patients with diabetic foot infections. At an average follow-up of 7 years,
      the soft tissue cushion remained in a stable position, without ulceration. Also,
      patient satisfaction was high with the Syme level of amputation using the
      modified technique. 

PMID- 24021267
TI  - Genetically modified mouse models for oral drug absorption and disposition.
AB  - Intestinal absorption is an essential step in the therapeutic use of most orally
      administered drugs and often mediated by enterocyte transmembrane transporters.
      Here we discuss several of these drug transport systems and knockout mouse models
      to study them. These studies showed that Multidrug resistance-associated protein
      2 (Mrp2) can limit intestinal drug absorption. Organic cation transporter n1
      (Octn1) and Octn2 might also facilitate intestinal drug absorption, although
      direct in vivo evidence is lacking. On the other hand, intestinal uptake of drugs
      is facilitated by the Equilibrative nucleoside transporter 1 (Ent1), Mrp3 and
      possibly Mrp4. No significant role in intestinal absorption for Oct1 and Oct2 or
      for Organic anion-transporting polypeptides (Oatp) 1a and 1b was found so far. 

PMID- 24021268
TI  - Seizure-induced excitotoxicity: Just considering it could be a fallacy: Comment
      on: Cianfoni A, Caulo M, Cerase A, et al. Seizure-induced brain lesions: a wide
      spectrum of variably reversible MRI abnormalities (in press).

PMID- 24021269
TI  - PET-CT after radiofrequency ablation of colorectal liver metastases: suggestions
      for timing and image interpretation.
AB  - INTRODUCTION: The main area of concern regarding radiofrequency ablation (RFA) of
      colorectal liver metastases is the risk of developing a local site recurrence
      (LSR). Reported accuracy of PET-CT in detecting LSR is high compared to
      morphological imaging alone, but no internationally accepted criteria for image
      interpretation have been defined. Our aim was to assess criteria for FDG PET-CT
      image interpretation following RFA, and to define a timetable for follow-up
      detection of LSR. METHODS: Patients who underwent RFA for colorectal liver
      metastases between 2005 and 2011, with FDG-PET follow-up within one year after
      treatment were included. Results of repeat FDG-PET scans were evaluated until a
      LSR was diagnosed. Results. One hundred-seventy scans were obtained for 79
      patients (179 lesions), 57 scans (72%) were obtained within 6 months of
      treatment. Thirty patients developed local recurrence; 29 (97%) within 1 year.
      Only 2% of lesions of <1cm and 4% of <2 cm showed a LSR. CONCLUSION: The majority
      of local site recurrences are diagnosed within one year after RFA. Regular follow
      up using FDG PET-CT within this period is advised, so repeated treatment can be
      initiated. Rim-shaped uptake may be present until 4-6 months, complicating
      evaluation. The benefit in the follow-up of lesions <2 cm may be limited.

PMID- 24021270
TI  - Confirmatory analysis of stanozolol metabolites in bovine, pig and sheep urines
      using an optimized clean-up and liquid chromatography-tandem mass spectrometry.
AB  - This paper describes a new liquid chromatography-tandem mass spectrometric (LC
      MS/MS) method for the analysis of three stanozolol metabolites (16beta
      hydroxystanozolol, 3'-hydroxystanozolol, and 4beta-hydroxystanozolol) in urines
      of animal origins. The solid-phase extraction (SPE) clean-up procedure was
      optimized to reduce the matrix effects in the LC-MS/MS analysis and to enhance
      recovery. Four different approaches were tested to prepare the sample, which
      include anion, and cation mixed-mode ion exchange, reversed-phase and normal
      phase SPE cartridges. Mixed-mode anion exchange Strata-XL-A SPE column with
      diethyl ether elution yielded the best values. The separation of metabolites was
      optimized on Kinetex XB column using isocratic elution. The best mobile phase
      composition was achieved at the acidic pH with 0.1% (v/v) formic acid in water
      and methanol composition. The main advantages of the approach applied in the
      present study over other known methods include the single step SPE clean-up,
      relatively fast separation on HPLC column packed with core-shell particles, and
      lowering the limit of detection of target metabolites to the range between 0.05
      and 0.15MUg/l. Additionally, the developed method was successfully validated for
      the first time for three species in accordance with the European Union (EU)
      2002/657/EC decision. Finally, the efficiency of method was demonstrated by
      analyzing incurred samples. 

PMID- 24021271
TI  - Management of infections in cirrhotic patients: report of a consensus conference.
AB  - The statements produced by the consensus conference on infection in end-stage
      liver disease promoted by the Italian Association for the Study of the Liver, are
      here reported. The topics of epidemiology, risk factors, diagnosis, prophylaxis,
      and treatment of infections in patient with compensated and decompensated liver
      cirrhosis were reviewed by a scientific board of experts who proposed 26
      statements that were graded according to level of evidence and strength of
      recommendation, and approved by an independent jury. Each topic was explored
      focusing on the more relevant clinical questions. By systematic literature search
      of available evidence, comparison and discussion of expert opinions, pertinent
      statements answering specific questions were presented and approved. Short
      comments were added to explain the basis for grading evidence particularly on
      case of controversial areas. 

PMID- 24021272
TI  - Cytological assessment of Barr bodies using aceto-orcein and papanicolaou stains
      in buccal mucosal smears and their sex estimation efficacy in an Indian sample.
AB  - OBJECTIVE: Buccal epithelial cells in saliva traces found at a crime scene can be
      used for sex determination by examining the presence of Barr bodies in the
      nucleus. Papanicolaou (PAP) and fluorescent stains, among others, have been used
      in the past. Aceto-orcein (AO) is a relatively unexplored staining technique for
      this purpose. This study aims to assess the efficacy of sex determination using
      AO and PAP stains for the detection of Barr bodies in buccal mucosal scrapes.
      STUDY DESIGN: Buccal scrapings were collected from 120 healthy individuals (60
      males and 60 females). They were stained with AO and PAP. Fifty cells in each
      sample were analyzed for identification of Barr bodies. Samples with a presence
      of Barr bodies <=5% were recorded as male and those with >5% were recorded as
      female. The percentage accuracy in determining sex using both stains was
      evaluated. RESULTS: The percentage of Barr bodies in AO-stained slides ranged
      from 5 to 32 among females and from 0 to 8 in males, while with PAP the ranges
      recorded were 4-20 in females and 0-5 in males (p < 0.001). The sensitivity and
      specificity of AO for detecting sex accurately was around 98.3 and 95% for PAP.
      CONCLUSION: Sex determination using Barr bodies in the buccal cells is a simple
      method that provides up to 95-98% accuracy; making it a significant accessory for
      sex determination. AO proved to be a better stain than PAP for visualizing
      nuclear details, and its staining time was remarkably shorter. It also
      demonstrated enhanced sex estimation efficacy compared to PAP.

PMID- 24021273
TI  - Usefulness of US to show subclinical joint abnormalities in asymptomatic feet of
      RA patients compared to healthy controls.
AB  - OBJECTIVES: The aim of the present study was to demonstrate the utility of
      ultrasound to show subclinical feet disease in RA. METHODS: The foot joints
      (talocrural, talocalcaneal, talonavicular, naviculocuneiform, calcaneocuboid, 5th
      tarsometatarsal and 1st to 5th metatarsophalangeal [MTP] joints) of 50 healthy
      subjects and 50 RA patients, with asymptomatic feet, were compared bilaterally.
      Statistical significance was set at 5%. RESULTS: Twenty-two joints were examined
      per individual (2200 in the entire sample). Significantly higher values were
      found in the RA group regarding quantitative synovitis in all joints recesses
      (p<0.003), the presence of synovitis (p<0.035) (except the 5thtarsometatarsal and
      3rdMTP joint), power Doppler (PD) signals (p<0.029) (talocalcaneal,
      talonavicular, 1st, 2nd, 3rd and 4thMTP joints) and bone erosion (p<0.003)
      (except for the talocrural and talocalcaneal joints). Synovitis, PD signals and
      erosion were observed in 18.3% and 3.05% (p<0.001), 5.77% and 0.22% (p<0.001) and
      34.45% and 2.85% (p<0.001) of the RA group and control group, respectively.
      Greater DAS-28, HAQ and FFI values were associated with ultrasound findings in
      only some joints (p<0.046). Interobserver agreement was <=0.686 for semi
      quantitative synovitis, <=0.641 for quantitative synovitis, <=0.474 for PD
      signals and <=1.000 for erosion. Low Cohen Kappa values were found in the
      correlation between radiography and ultrasound (0.084-0.400). CONCLUSIONS.
      Ultrasound on RA asymptomatic feet demonstrated a significantly greater number of
      inflammatory changes in current activity (synovitis, PD signals) and sequelae
      (erosion) in comparison to control subjects. In the midfoot, the talonavicular
      joint has the greatest number of ultrasound findings.

PMID- 24021275
TI  - Reconciling hypertriglyceridemic waist paradox: a meticulous maneuver between
      Scylla of "confounding bias" and Charybdis of "over-adjustment".

PMID- 24021276
TI  - Partial anomalous pulmonary venous return in adults with prior curative
      congenital heart surgery detected by cross-sectional imaging techniques.

PMID- 24021274
TI  - Oriented divisions, fate decisions.
AB  - During development, the establishment of proper tissue architecture depends upon
      the coordinated control of cell divisions not only in space and time, but also
      direction. Execution of an oriented cell division requires establishment of an
      axis of polarity and alignment of the mitotic spindle along this axis.
      Frequently, the cleavage plane also segregates fate determinants, either
      unequally or equally between daughter cells, the outcome of which is either an
      asymmetric or symmetric division, respectively. The last few years have witnessed
      tremendous growth in understanding both the extrinsic and intrinsic cues that
      position the mitotic spindle, the varied mechanisms in which the spindle
      orientation machinery is controlled in diverse organisms and organ systems, and
      the manner in which the division axis influences the signaling pathways that
      direct cell fate choices. 

PMID- 24021277
TI  - The crystal structure of a novel phosphopantothenate synthetase from the
      hyperthermophilic archaea, Thermococcus onnurineus NA1.
AB  - Pantothenate is the essential precursor of coenzyme A (CoA), a fundamental
      cofactor in all aspects of metabolism. In bacteria and eukaryotes, pantothenate
      synthetase (PS) catalyzes the last step in the pantothenate biosynthetic pathway,
      and pantothenate kinase (PanK) phosphorylates pantothenate for its entry into the
      CoA biosynthetic pathway. However, genes encoding PS and PanK have not been
      identified in archaeal genomes. Recently, a comparative genomic analysis and the
      identification and characterization of two novel archaea-specific enzymes show
      that archaeal pantoate kinase (PoK) and phosphopantothenate synthetase (PPS)
      represent counterparts to the PS/PanK pathway in bacteria and eukaryotes. The
      TON1374 protein from Thermococcus onnurineus NA1 is a PPS, that shares 54%
      sequence identity with the first reported archaeal PPS candidate, MM2281, from
      Methanosarcina mazei and 91% sequence identity with TK1686, the PPS from
      Thermococcus kodakarensis. Here, we report the apo and ATP-complex structures of
      TON1374 and discuss the substrate-binding mode and reaction mechanism.

PMID- 24021278
TI  - MD-2-dependent human Toll-like receptor 4 monoclonal antibodies detect
      extracellular association of Toll-like receptor 4 with extrinsic soluble MD-2 on
      the cell surface.
AB  - MD-2 is essential for lipopolysaccharide (LPS) recognition of Toll-like receptor
      4 (TLR4) but not for cell surface expression. The TLR4/MD-2 complex is formed
      intracellularly through co-expression. Extracellular complex formation remains a
      matter for debate because of the aggregative nature of secreted MD-2 in the
      absence of TLR4 co-expression. We demonstrated extracellular complex formation
      using three independent monoclonal antibodies (mAbs), all of which are specific
      for complexed TLR4 but unreactive with free TLR4 and MD-2. These mAbs bound to
      TLR4-expressing Ba/F3 cells only when co-cultured with MD-2-secreting Chinese
      hamster ovary cells or incubated with conditioned medium from these cells. All
      three mAbs bound the extracellularly formed complex indistinguishably from the
      intracellularly formed complex in titration studies. In addition, we demonstrated
      that two mAbs lost their affinity for TLR4/MD-2 on LPS stimulation, suggesting
      that these mAbs bound to conformation-sensitive epitopes. This was also found
      when the extracellularly formed complex was stimulated with LPS. Additionally, we
      showed that cell surface TLR4 and extrinsically secreted MD-2 are capable of
      forming the functional complex extracellularly, indicating an additional or
      alternative pathway for the complex formation.

PMID- 24021279
TI  - MicroRNA-130b targets Fmr1 and regulates embryonic neural progenitor cell
      proliferation and differentiation.
AB  - Fragile X syndrome, one of the most common forms of inherited mental retardation,
      is caused by expansion of the CGG repeat in the 5'-untranslated region of the X
      linked Fmr1 gene, which results in transcriptional silencing and loss of
      expression of its encoded protein FMRP. The loss of FMRP increases proliferation
      and alters fate specification in adult neural progenitor cells (aNPCs). However,
      little is known about Fmr1 mRNA regulation at the transcriptional and post
      transcriptional levels. In the present study, we report that miR-130b regulated
      Fmr1 expression by directly targeting its 3'-untranslated region (3' UTR). Up
      regulation of miR-130b in mouse embryonic neural progenitor cells (eNPCs)
      decreased Fmr1 expression, markedly increased eNPC proliferation and altered the
      differentiation tendency of eNPCs, suggesting that antagonizing miR-130b may be a
      new therapeutic entry point for treating Fragile X syndrome.

PMID- 24021280
TI  - Vascular VPO1 expression is related to the endothelial dysfunction in
      spontaneously hypertensive rats.
AB  - Reactive oxygen species (ROS) contributes to endothelial dysfunction that is
      involved in the pathogeneses of hypertension. Vascular peroxidase 1 (VPO1) can
      utilize ROS to catalyze peroxidative reactions, possibly enhancing endothelial
      dysfunction. This study is to identify VPO1's involvement in endothelial
      dysfunction and hypertension. Sixty-four spontaneously hypertensive rats (SHRs)
      and 64 age-matched, bodyweight controlled normotensive Wistar-Kyoto rats (WKYs)
      were randomly grouped and studied at the age of 5, 8, 13 and 20 weeks (16
      animals, each). Blood pressure and vasodilator responses to acetylcholine in
      aortic rings were observed. The expressions of VPO1 and endothelial NO synthase
      (eNOS) in aortas were assessed by quantitative reverse transcription-PCR and
      western blotting analysis. Plasma concentrations of hydrogen peroxide (H2O2) and
      NO, NOX activity, hypochlorous acid (HOCl) production, and 3-nitrotyrosine
      content in aortic homogenates were also determined in this study. Along with the
      development of hypertension in SHR rats, VPO1 expression was up-regulated
      together with a significant increase in NOX activity, HOCl production, 3
      nitrotyrosine content, and plasma H2O2 level compared with WKYs at 8, 13 and 20
      weeks of age. In contrast, blood NO levels were decreased and aortic relaxation
      to acetylcholine was deteriorated in SHRs. The over-expression of VPO1 during the
      development of hypertension, accompanied by the endothelial dysfunction, the
      decreased NO levels, the elevated NOX and ROS activities, indicates a clear
      connection between VPO1 gene and hypertension. VPO1 may pathogenetically
      contribute to hypertension via signal pathways involving NOX-H2O2-VPO1-HOCl or
      JNK/p38 MAPK although further studies are needed to determine the precise
      mechanisms.

PMID- 24021281
TI  - Focal adhesion kinase mediates beta-catenin signaling in periodontal ligament
      cells.
AB  - Periodontal ligament (PDL) cells convert the orthodontic forces into biological
      responses by secreting signaling molecules to induce modeling of alveolar bone
      and tooth movement. Beta-catenin pathway is activated in response to mechanical
      loading in PDL cells. The upstream signaling pathways activated by mechanical
      loading resulting in the activation of beta-catenin pathway through Wnt
      independent mechanism remains to be characterized. We hypothesized that
      mechanical loading induces activation of beta-catenin signaling by mechanisms
      that dependent on focal adhesion kinase (FAK) and nitric oxide (NO). We found
      that mechanical or pharmacological activation of beta-catenin signaling in PDL
      cells upregulated the expression of beta-catenin target genes. Pre-treatment of
      PDL cells with FAK inhibitor-14 prior to mechanical loading abolished the
      mechanical loading-induced phosphorylation of Akt and dephosphorylation of beta
      catenin. PDL cells pre-treated with NO donor or NO inhibitor and subjected to
      mechanical loading. Western blot analysis showed that the mechanical loading or
      pre-treatment with NO donor increased the levels of dephosphorylated beta
      catenin, pAkt, and pGSK-3beta. Pre-treatment with NO inhibitor blocked the
      mechanical loading-induced phosphorylation of Akt and dephosphorylation of beta
      catenin. These data indicate that mechanical loading-induced beta-catenin
      stabilization in PDL cells involves phosphorylation of Akt by two parallel
      pathways requiring FAK and NO.

PMID- 24021282
TI  - Ascorbate-induced generation of 5-hydroxymethylcytosine is unaffected by varying
      levels of iron and 2-oxoglutarate.
AB  - Tet (ten-eleven translocation) methylcytosine dioxygenases, which belong to the
      iron and 2-oxoglutarate (2OG)-dependent dioxygenase superfamily, convert 5
      methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. We recently
      reported that ascorbate (vitamin C) induces Tet-mediated generation of 5hmC. To
      initially delineate the role of ascorbate on 5hmC generation, we analyzed whether
      the effect of ascorbate is dependent upon the conditions of other components
      involved in the hydroxylation of 5mC catalyzed by Tet. We found that removing
      iron from the culture medium did not affect the induction of 5hmC by ascorbate
      (10 MUM) in mouse embryonic fibroblasts (MEFs). The effect of ascorbate did not
      involve an increased expression of Tet1-3 or isocitrate dehydrogenases (IDH1-2),
      the enzymes responsible for producing 2OG. Interestingly, MEFs cultured with
      different concentrations of glucose, a major precursor of 2OG, exhibited nearly
      identical responses to ascorbate treatment. Further, blocking the uptake of the
      reduced form of vitamin C, ascorbic acid, through the sodium-dependent vitamin C
      transporters (SVCTs) inhibited the effect of ascorbate on 5hmC. However,
      inhibition of the facilitative glucose transporters (GLUTs), which mediate the
      incorporation of the oxidized form of vitamin C, dehydroascorbic acid (DHA), did
      not modify the ability of ascorbate to induce 5hmC generation. These results
      indicate that the effect of ascorbate on 5hmC is not dependent upon iron uptake,
      the expression of Tet and IDH, or the production of 2OG, suggesting that
      ascorbate may directly participate in the generation of 5hmC, most likely as a
      cofactor of Tet.

PMID- 24021283
TI  - p27(Kip1) inhibits tissue factor expression.
AB  - BACKGROUND: The cyclin-dependent kinase inhibitor (CDKI) p27(Kip1) regulates cell
      proliferation and thus inhibits atherosclerosis and vascular remodeling.
      Expression of tissue factor (TF), the key initator of the coagulation cascade, is
      associated with atherosclerosis. Yet, it has not been studied whether p27(Kip1)
      influences the expression of TF. METHODS AND RESULTS: p27(Kip1) overexpression in
      human aortic endothelial cells was achieved by adenoviral transfection. Cells
      were rendered quiescent for 24h in 0.5% fetal-calf serum. After stimulation with
      TNF-alpha (5 ng/ml), TF protein expression and activity was significantly reduced
      (n=4; P<0.001) in cells transfected with p27(Kip1). In line with this, p27(Kip1)
      overexpression reduced cytokine-induced TF mRNA expression (n=4; P<0.01) and TF
      promotor activity (n=4; P<0.05). In contrast, activation of the MAP kinases p38,
      ERK and JNK was not affected by p27(Kip1) overexpression. CONCLUSION: This in
      vitro study suggests that p27(Kip1) inhibits TF expression at the transcriptional
      level. These data indicate an interaction between p27(Kip1) and TF in important
      pathological alterations such as atherosclerosis and vascular remodeling.

PMID- 24021284
TI  - Mutant gammaPKC that causes spinocerebellar ataxia type 14 upregulates Hsp70,
      which protects cells from the mutant's cytotoxicity.
AB  - Several missense mutations in the protein kinase Cgamma (gammaPKC) gene have been
      found to cause spinocerebellar ataxia type 14 (SCA14), an autosomal dominant
      neurodegenerative disease. We previously demonstrated that the mutant gammaPKC
      found in SCA14 is misfolded, susceptible to aggregation and cytotoxic. Molecular
      chaperones assist the refolding and degradation of misfolded proteins and
      prevention of the proteins' aggregation. In the present study, we found that the
      expression of mutant gammaPKC-GFP increased the levels of heat-shock protein 70
      (Hsp70) in SH-SY5Y cells. To elucidate the role of this elevation, we
      investigated the effect of siRNA-mediated knockdown of Hsp70 on the aggregation
      and cytotoxicity of mutant gammaPKC. Knockdown of Hsp70 exacerbated the
      aggregation and cytotoxicity of mutant gammaPKC-GFP by inhibiting this mutant's
      degradation. These findings suggest that mutant gammaPKC increases the level of
      Hsp70, which protects cells from the mutant's cytotoxicity by enhancing its
      degradation.

PMID- 24021285
TI  - Apoptosis signal-regulating kinase-1 aggravates ROS-mediated striatal
      degeneration in 3-nitropropionic acid-infused mice.
AB  - Apoptosis signal-regulating kinase-1 (ASK1), an early signaling element in the
      cell death pathway, has been suggested to participate in the pathology of
      neurodegenerative diseases, which may be associated with environmental factors
      that impact the diseases. Although it is not entirely elucidated, 3
      nitropropionic acid (3-NP) provokes mitochondrial dysfunction and selectively
      forms striatal lesions similar to those found in Huntington's disease. The
      current study investigated whether ASK1 is involved in striatal pathology
      following chronic systemic infusion of 3-NP. The results show that ASK1 acts as a
      primary mediator of there active oxygen species (ROS) cell death signal cascade
      in the 3-NP-damaged striatal region by disrupting the positive feedback cycle. In
      3-NP-infused striatal lesions, ROS increased ASK1. Superoxide dismutase
      transgenic (SOD-tg) mice reduced ASK1by scavenging ROS, and reduction of
      ASK1leads to a reduction in cell death. However, ASK1 down-regulation in 3-NP
      infusion mice also decreased striatal cell death without scavenging ROS. In
      contrast decreasing cell death by si-ASK1 treatment along with 3-NP in both SOD
      tg and wild-type mice (wt), cell death rebounded when ASK1 peptide was added to
      SOD tg mice. The present study suggests that ROS-inducing ASK1 may be an
      important step in the pathogenesis of 3-NP infused striatal lesions in murine
      brains.

PMID- 24021286
TI  - Lifestyle interventions reduce cardiovascular risk in patients with coronary
      artery disease: a randomized clinical trial.
AB  - BACKGROUND: Nurse-led interventions have proven beneficial to reduce estimated
      cardiovascular risk. AIM: The purpose of this study was to evaluate the effect of
      systematic, nurse-led individual lifestyle counseling sessions on the reduction
      of 10-year cardiovascular risk scores in patients with coronary artery disease
      (CAD). METHODS: This was a randomized clinical trial of CAD patients treated at a
      tertiary referral hospital. The intervention group received nurse-led guidance by
      means of five face-to-face sessions and telephone contact over the course of one
      year, starting three months after hospital discharge. Exercise and dietary goals
      were set for each patient and monitored at each session. The control group
      received standard medical advice. Patients were stratified by Framingham risk
      score and compared at the end of the follow-up period. RESULTS: The final sample
      comprised 74 patients, 38 in the intervention group and 36 in the control group.
      Mean age was 58 +/- 9 years; 74% of patients were male. A 1.7 point (-13.6%)
      reduction in risk score was recorded in the intervention group, vs a 1.2 point
      increase in risk score (+11%) in the control group (p=0.011). Significant between
      group differences were detected for weight (intervention, 78 +/- 14 kg at
      baseline vs 77 +/- 14 kg at study end; control, 78 +/- 15 kg vs 79 +/- 15 kg;
      p=0.04), systolic blood pressure (intervention, 136 +/- 22 mm Hg vs 124 +/- 15 mm
      Hg; control, 126 +/- 15 mm Hg vs 129 +/- 16 mm Hg; p=0.005), and diastolic blood
      pressure (intervention, 82 +/- 10 mm Hg vs 77 +/- 09 mm Hg; control, 79 +/- 09 mm
      Hg vs 80 +/- 10 mm Hg; p=0.02). CONCLUSION: Structured and systematic nurse-led
      lifestyle counseling effectively reduced cardiovascular risk score.

PMID- 24021287
TI  - A decrease of the butyrate-producing species Roseburia hominis and
      Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative
      colitis.
AB  - OBJECTIVE: Bacteria play an important role in the onset and perpetuation of
      intestinal inflammation in inflammatory bowel disease (IBD). Unlike in Crohn's
      disease (CD), in which dysbiosis has been better characterised, in ulcerative
      colitis (UC), only small cohorts have been studied and showed conflicting data.
      Therefore, we evaluated in a large cohort if the microbial signature described in
      CD is also present in UC, and if we could characterise predominant dysbiosis in
      UC. To assess the functional impact of dysbiosis, we quantified the bacterial
      metabolites. DESIGN: The predominant microbiota from 127 UC patients and 87 age
      and sex-matched controls was analysed using denaturing gradient gel
      electrophoresis (DGGE) analysis. Differences were quantitatively validated using
      real-time PCR. Metabolites were quantified using gas chromatography-mass
      spectrometry. RESULTS: Based on DGGE analysis, the microbial signature previously
      described in CD was not present in UC. Real-time PCR analysis revealed a lower
      abundance of Roseburia hominis (p<0.0001) and Faecalibacterium prausnitzii
      (p<0.0001) in UC patients compared to controls. Both species showed an inverse
      correlation with disease activity. Short-chain fatty acids (SCFA) were reduced in
      UC patients (p=0.014), but no direct correlation between SCFA and the identified
      bacteria was found. CONCLUSIONS: The composition of the fecal microbiota of UC
      patients differs from that of healthy individuals: we found a reduction in R
      hominis and F prausnitzii, both well-known butyrate-producing bacteria of the
      Firmicutes phylum. These results underscore the importance of dysbiosis in IBD
      but suggest that different bacterial species contribute to the pathogenesis of UC
      and CD.

PMID- 24021288
TI  - Hepatotoxic botanicals - an evidence-based systematic review.
AB  - PURPOSE: Herbal medicines have been increasingly used worldwide. However, the
      potential harms of these herbs have been noticed most recently following
      hepatotoxicity with ingestion of herbal remedies. The aim of this review is to
      evaluate the evidence of hepatotoxic effects linked to use of herbal
      preparations. METHOD: Electronic search was performed by searching several
      databases: PubMed, HerbMed, Google Scholar, Scopus, Cochrane Database of
      Systematic Reviews and Cochrane Library using both Latin and common names of
      several herbs. Language was restricted to English and articles were selected for
      relevance reporting incidence of hepatotoxicity associated with use of herbal
      products in human. RESULTS: From a total of 565 relevant reviews and articles,
      254 met our inclusion criteria and were analyzed. Serious hepatotoxic events
      associated with various herbal products alone or in combination with other drugs
      have been reported. Linking to herbal constituents the spectrum of liver toxicity
      includes elevated liver enzymes, acute or chronic hepatitis, cholestasis, hepatic
      necrosis, fibrosis, and cirrhosis, as well as acute liver failure and hepatic
      veno-occlusive disease. CONCLUSION: The hepatotoxicity of herbs was extensively
      acknowledged. As the use of natural medicine increases, the risk of liver
      toxicity and drug interaction increase as well. Accordingly, herbal remedies have
      been known as hepatotoxins causing several liver damages. Further scientific
      studies with high and good quality are needed to identify toxic compounds and
      understand the exact mechanism of hepatotoxicity-induced by herbs. The adverse
      effects of herbal products must be fully reported as well as extensive education
      of healthcare providers must be provided in order to reduce danger of alternative
      medicines.

PMID- 24021289
TI  - Evaluation of renal adverse effects of combination anti-retroviral therapy
      including tenofovir in HIV-infected patients.
AB  - PURPOSE: In order to maintain plasma HIV-RNA concentration in HIV-infected
      patients, below the detection limit combination anti-retroviral therapy (cART)
      are used. Although the nucleoside/nucleotide reverse transcriptase inhibitor,
      tenofovir disoproxil fumarate (TDF) is a first-line drug commonly used, it is
      associated with renal dysfunction. Nevertheless, only few clinical studies have
      focused on TDF in combination with new anti-HIV drugs, including the protease
      inhibitor (PI) darunavir (DRV), or the integrase strand transfer inhibitor
      (INSTI) raltegravir (RAL). Here we report the influence of such cART involving
      TDF on renal function. METHODS: We retrospectively investigated 68 patients under
      cART that included TDF between November 2004 and May 2012. We used hospital
      records to establish each patient's background and characteristics, CD4 cell
      count, plasma HIV-RNA concentration, drug combinations, renal function, and anti
      retrovial therapy history. RESULTS: In all patients who had received cART, the
      plasma HIV-RNA concentration had fallen to less than 40 copies/mL by week 24
      after the start of the therapy, and an increase in the CD4 cell count was
      observed. For each drug used in combination with TDF, the plasma HIV-RNA
      concentration and CD4 cell count showed a similar trend. After week 12, the
      estimated glomerular filtration rate (eGFR) had significantly decreased in all
      patients. The eGFR was significantly lower in those received PI on week 24 and in
      those received INSTI on week 12. The eGFR was significantly reduced in PI group
      who received atazanavir + ritonavir (ATV/RTV) on week 60. The eGFR in the DRV/RTV
      group tended to decrease. The eGFR in the PI and ATV/RTV group was significantly
      lower than in the efavirenz (EFV) group on week 96. CONCLUSION: It selecting
      drugs to include in combination therapy of HIV-infected patients, consideration
      should be given to the risk of renal dysfunction. There is a need to monitor
      renal function when TDF is combined with ATV/RTV, DRV/RTV or RAL.

PMID- 24021290
TI  - Carnitine and sepsis: a review of an old clinical dilemma.
AB  - PURPOSE: The precise role of carnitine as the key regulator of lipid metabolism
      in sepsis is unclear. In this review, available experimental as well as clinical
      evidences regarding the probable beneficial effects of carnitine in sepsis were
      evaluated. METHOD: A comprehensive literature search was performed in the related
      medical databases. Related experimental and clinical studies were included.
      RESULTS AND CONCLUSION: The plasma and tissue level of carnitine or its
      derivatives in septic condition is variable and inconclusive. Survival and
      outcomes are considered in only few studies. Despite its favorable safety
      profile, due to limited clinical evidence, it seems reasonable not to currently
      consider carnitine as a mandatory and beneficial supplement under septic
      conditions. Further well-designed, standard clinical trials are warranted in this
      regards.

PMID- 24021291
TI  - Novel population pharmacokinetic method compared to the standard noncompartmental
      approach to assess bioequivalence of iron gluconate formulations.
AB  - PURPOSE: Iron-containing products are atypical in terms of their pharmacokinetic
      properties because iron is only removed by plasma sampling and is non-linear.
      This study aims to present a novel way of assessing the relative bioavailability
      of two sodium ferric gluconate complex (SFGC) formulations and compare this
      approach to a standard previously published noncompartmental approach. METHODS:
      Data were from open-label, randomized, single-dose studies (Study 1 was parallel
      whereas Study 2 was crossover). Subjects with low but normal iron levels were
      infused IV SFGC in sucrose by GeneraMedix Inc. and/or Ferrlecit (r) Injection
      (Watson Laboratories Inc.). In Study 1 (n=240), 125 mg was infused over 10
      minutes. In Study 2 (n=29), 62.5 mg was infused over 30 minutes. Samples were
      assayed for total iron (TI) and transferrin-bound iron (TBI) over 36 hours (Study
      1) or 72 hours (Study 2) post-dose. Studies 1 and 2 used standard
      noncompartmental analysis. Study 2 also used population PK (PPK) analyses with
      ADAPT 5(r). The final model predicted SFGC area-under-the-curve (AUCpred) and
      maximal concentration (Cmaxpred). Analyses of variance was conducted on ln
      transformed PK parameters. Ratios of means and 90% confidence intervals (CIs)
      were estimated. Bioequivalence was demonstrated if values were within 80-125%.
      RESULTS: For Study 1, ratios and 90% CIs for TI baseline-corrected Cmax and AUC0
      36 were 100.4 (96.5 - 104.5) and 99.7 (94.2 - 105.5). For TBI, results for TI
      baseline-corrected Cmax and AUC0-36 were 86.8 (82.7 - 91.1) and 92.4 (85.6 -
      99.7). For Study 2, a multi-compartmental model simultaneously described the PK
      of TI, TBI and SFGC. Ratios and 90% CIs for SFGC Cmaxpred and AUCpred were 89.9
      (85.9 - 94.0) and 89.7 (85.7 - 93.9), while ratios and 90% CI obtained from the
      noncompartmental analysis of Study 2 did not meet BE criteria because of low
      power. CONCLUSIONS: Both the standard and PPK modeling approach suggested
      bioequivalence between the iron products. However, with the PPK method, less
      subjects were required to meet study objectives compared to the standard
      noncompartmental approach which required considerably more subjects (29 vs 240).

PMID- 24021292
TI  - Liquid dosage forms extemporaneously prepared from commercially available
      products - considering new evidence on stability.
AB  - Although the world's population is ageing and as a result of this an increasing
      number of patients are experiencing difficulty in swallowing, there remains a
      lack of commercially available oral liquids for both these older and paediatric
      patients. This presents a problem to health care professionals, especially the
      pharmacist in practice, who is often required to provide a solution for these
      patients by preparing oral liquids extemporaneously from commercially available
      products. Preparation of these oral liquids is challenging, both due to the lack
      of pharmacopoeial and stability-indicating formulae and the fact that their
      stability is not only determined by the active pharmaceutical ingredient, but
      also the ability of excipients from the commercial product to interact with each
      other and the active pharmaceutical ingredient. This increases the complexity of
      the stability considerations to be taken into account within these oral liquids,
      highlighting the number of parameters to be considered in the extemporaneous
      preparation of oral liquids. This paper presents new evidence on the stability of
      42 oral liquids prepared from commercially available products, reported on in the
      literature since the previous review published in 2006. However, unlike the
      previous review where the stability concerns in 7.2% of the extemporaneously
      prepared oral liquids were mainly due to interaction between the active
      pharmaceutical ingredients and the excipients in the commercial product, most of
      these stability considerations have been recognised and this has resulted in the
      authors proposing solutions to these problems prior to the extemporaneous
      preparation of the oral liquid. As such this paper also focuses on the increased
      level of research that has been undertaken to solve previous issues related to
      stability, especially in terms of the use of commercial products, which is common
      practice in the extemporaneous preparation of oral liquids.

PMID- 24021293
TI  - Evaluation of brain targeting and mucosal integrity of nasally administrated
      nanostructured carriers of a CNS active drug, clonazepam.
AB  - PURPOSE: The aim of the study was to target clonazepam, a CNS active drug, to the
      brain through the non-invasive intranasal (in) route using of nanocarriers with
      proven safety METHOD: in clonazepam nanocarriers were prepared by mixing
      isopropyl myristate, Tween 80, Cremophor EL or lecithin, polyethylene glycol 200,
      propylene glycol or ethanol in different ratios with water. in-vitro
      characterization of the nanocarriers was done by various methods including:
      polarized light microscopy, particle size determination, viscosity measurements
      and drug release studies. in-vivo study comparing intranasal and intravenous
      administration was performed. The drug targeting efficiency (DTE %) and direct
      nose to brain transport percentage (DTP %) were calculated and nasal integrity
      assessment was carried out. RESULTS: The obtained formulae had particle size
      below 100 nm favoring rapid direct nose to brain transport and the time for 100%
      drug release (T100%) depended on systems composition. Plasma Tmax of clonazepam
      nanostructured carriers varied from 10-30 min., while their brain Tmax did not
      exceed 10 min, in comparison with 30 min for iv solution. Although there was no
      significant difference (p>0.05) between the plasma AUC0-infinity of the different
      tested nanocarriers and intravenous one, the increase in brain AUC 0 -infinity of
      different nasal formulations in comparison to that of iv administration (3.6 -7.2
      fold) confirms direct nose to brain transport via olfactory region. Furthermore,
      DTE and DTP% confirmed brain targeting of clonazepam following intranasal
      administration. CONCLUSION: The results confirmed that intranasal nanocarriers
      were proved to be safe alternative for iv clonazepam delivery with rapid nose to
      brain transport.

PMID- 24021294
TI  - Design and pharmaceutical evaluation of a nano-enabled crosslinked multipolymeric
      scaffold for prolonged intracranial release of Zidovudine.
AB  - PURPOSE: Nanomedicine explores and allows for the development of drug delivery
      devices with superior drug uptake, controlled release and fewer drug side
      effects. This study explored the use of nanosystems to formulate an implantable
      drug delivery device capable of sustained zidovudine release over a prolonged
      period. METHODS: Pectin and alginate nanoparticles were prepared by applying a
      salting out and controlled gelification approach, respectively. The nanoparticles
      were characterized by attenuated total reflectance-fourier transform infrared
      spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), transmission
      electron microscopy (TEM) and dynamic light scattering (DLS) and were further
      evaluated for zidovudine (AZT) entrapment efficiency. Multipolymeric scaffolds
      were prepared by crosslinking carboxymethyl cellulose, polyethylene oxide and
      epsilon caprolactone for entrapment of zidovudine-loaded alginate nanoparticles
      to impart enhanced controlled release of zidovudine over the time period.
      Swelling and textural analysis were conducted on the scaffolds. Prepared
      scaffolds were treated with hydrochloric acid (HCl) to reduce the swelling of
      matrix in the hydrated environment thereby further controlling the drug release.
      Drug release studies in phosphate buffered saline (pH 7.4, 37 degrees C) were
      undertaken on both zidovudine-loaded nanoparticles and native scaffolds
      containing alginate nanoparticles. RESULTS: A higher AZT entrapment efficiency
      was observed in alginate nanoparticles. Biphasic release was observed with both
      nanoparticle formulations, exhibiting an initial burst release of drug within
      hours of exposure to PBS, followed by a constant release rate of AZT over the
      remaining 30 days of nanoparticle analysis. Exposure of the scaffolds to HCl
      served to reduce the drug release rate from the entrapped alginate nanoparticles
      and extended the AZT release up to 30 days. CONCLUSIONS: The crosslinked
      multipolymeric scaffold loaded with alginate nanoparticles and treated with 1%
      HCl showed the potential for prolonged delivery of zidovudine over a period of 30
      days and therefore may be a potential candidate for use as an implantable device
      in treating Aids Dementia Complex.

PMID- 24021295
TI  - Diabetes results in structural alteration of chondroitin sulfate in the urine.
AB  - PURPOSE: The assessment of the clinical significance of chondroitin sulfate in
      patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for
      the detection of the relationship between chondroitin sulfate (CS) structure and
      disease. METHODS: Healthy control (n=15), type 2 diabetic patients with
      normalbuminuria (n=12), and patients with microalbuminuria (n=13) were enrolled
      in the study. Total sulfated glycosaminoglycans (GAGs) concentration in the first
      morning urine was evaluated by 1,9-dimethylmethylene blue method and the
      composition was determined by agarose gel electrophoresis. Urinary chondroitin
      sulfate was quantified by a combination of treatment with specific lyase
      digestions and separation of products by SAX-HPLC. RESULTS: GAGs concentration
      significantly increased in diabetic patients with microalbuminuria compared to
      diabetic patients with normalbuminuria. Qualitative analysis of urinary GAGs
      revealed the presence of chondroitin sulfate, heparan sulfate, and low-sulphated
      chondroitin sulphate-protein complex (LSC-PG). There was a decrease in CS and an
      increase in LSC-PG in the urine of patients with diabetes compared to healthy
      controls. Moreover, in diabetic patients, chondroitin sulfate contains more 6
      sulfated disaccharide and less 4-sulfated disaccharide. There was a statistically
      significant difference in ratio of 6-sulfated disaccharide to 4-sulfated
      disaccharide among the three groups. CONCLUSIONS: GAGs were significantly
      increased in diabetic patients with microalbuminuria. The levels of urinary GAGs,
      ratio of LSC-PG/CS, as well as ratio of 6-sulfated to 4-sulfated disaccharides
      could be useful markers for diagnosis of patients with diabetic nephropathy.

PMID- 24021296
TI  - Intracellular uptake mechanism of lutein in retinal pigment epithelial cells.
AB  - PURPOSE: Lutein is a carotenoid mainly found in green leafy vegetables and is
      located in the macula lutea in the human eye. It has received much attention
      recently due to its preventive effect on age-related macular degeneration, and it
      has been consumed as a supplement. However, little information about the
      pharmacokinetic properties of lutein is available. Detailed knowledge of
      pharmacokinetic properties of lutein is needed for the development of
      pharmaceutics. In this study, we focused on the macular accumulation of lutein
      and investigated the uptake mechanism into human retinal pigment epithelial
      cells. METHODS: ARPE-19 cells were used for the study on the accumulation
      mechanism of lutein. The concentration of lutein was determined using an HPLC
      system. Involvement of scavenger class B type 1 (SR-B1) in the accumulation of
      lutein in ARPE-19 cells was suggested from the results of an inhibition study
      using block lipid transport 1 (BLT-1), a selective inhibitor of SR-B1. To
      investigate the involvement of SR-B1 in more detail, small interfering RNA
      (siRNA) was transfected and the mRNA and protein expression levels of SR-B1 were
      assessed by quantitative real-time reverse transcription polymerase chain
      reaction and Western blotting, respectively. RESULTS: We confirmed a sufficient
      siRNA knockdown effect in both mRNA and protein expression levels of SR-B1. We
      then found that lutein uptake was significantly decreased by siRNA knockdown of
      SR-B1. CONCLUSION: The uptake of lutein was significantly decreased by 40%
      compared with the control uptake level. This suggested that active transport of
      lutein into ARPE-19 cells is mainly via SR-B1, given the result that lutein
      uptake at 4oC was about 40% less that that at 37oC.

PMID- 24021297
TI  - A four-year, open-label, multi-center, randomized, two-arm study of Genotropin(r)
      in patients with idiopathic short stature: comparison of an individualized,
      target-driven treatment regimen to standard dosing of Genotropin(r) - analysis of
      two-year data.
AB  - BACKGROUND: Several models have been developed to predict growth response to
      growth hormone (GH) based on auxological and biochemical parameters for children
      with non-GH-deficient, idiopathic short stature (ISS). OBJECTIVE: To demonstrate
      if an individualized, formula-based, target-driven GH regimen for children with
      ISS would lead to a height (Ht) gain to -1.3 SDS during the first 24 months of
      treatment of this 4-year study, with less variability than with standard weight
      based dosing. METHODS: A 4-year, open-label, multi-center, randomized, two-arm
      study comparing formula-based dosing of Genotropin(r) GH from 0.18 to 0.7
      mg/kg/week versus standard FDA-approved ISS dosing of Genotropin(r) (0.37
      mg/kg/week). Subjects (n = 316, 89 females) were prepubertal, 3-14 years of age,
      bone age 3-10 years (m) and 3-9 years (f), naive to GH treatment, Ht SDS -3 to 
      2.25, Ht velocity <25th percentile for bone age, and peak GH >10 ng/ml. RESULTS:
      The majority (83%) of subjects had Ht SDS within the normal range by 2 years. All
      subjects displayed catch-up growth consistent with other studies of GH treatment
      of ISS. CONCLUSION: The formula-based therapy did not meet the primary endpoint
      achieving targeted gain with lower variability. No new safety concerns were
      found.

PMID- 24021298
TI  - Effect of partial weight-supported treadmill gait training on balance in patients
      with Parkinson disease.
AB  - OBJECTIVE: To investigate the role of conventional gait training and partial
      weight-supported treadmill gait training (PWSTT) in improving the balance of
      patients with Parkinson disease (PD). DESIGN: Prospective randomized controlled
      design. SETTING: National-level university tertiary hospital for mental health
      and neurosciences. PATIENTS: Sixty patients with PD fulfilling the United Kingdom
      Brain Bank PD diagnostic criteria were recruited from the neurology outpatient
      department and movement disorder clinic. METHODOLOGY: The patients were randomly
      assigned into 3 equal groups: (1) a control group that only received a stable
      dosage of dopaminomimetic drugs; (2) a conventional gait training (CGT) group
      that received a stable dosage of dopaminomimetic drugs and conventional gait
      training; and (3) a PWSTT group that received a stable dosage of dopaminomimetic
      drugs and PWSTT with unloading of 20% of body weight. The sessions for the CGT
      and PWSTT groups were provided for 30 minutes per day, 4 days per week, for 4
      weeks (16 sessions). OUTCOME MEASURES: The Unified Parkinson Disease Rating Scale
      (UPDRS) motor score, dynamic posturography, Berg Balance Scale, and Tinetti
      performance-oriented mobility assessment (POMA) were used as main outcome
      measures. RESULTS: A significant interaction effect was observed in the UPDRS
      motor score, mediolateral index, Berg Balance Scale, limits of stability (LOS)
      total score, POMA gait score, and balance score. Post-hoc analysis showed that in
      comparison with the control group, the PWSTT group had a significantly better
      UPDRS motor score, balance indices, LOS in 8 directions, POMA gait, and balance
      score. The CGT group had a significantly better POMA gait score compared with
      control subjects. Compared with the CGT group, the PWSTT group had a
      significantly better UPDRS motor score, mediolateral index, POMA gait score, and
      LOS total score. CONCLUSION: PWSTT may be a better interventional choice than CGT
      for gait and balance rehabilitation in patients with PD.

PMID- 24021299
TI  - Management of patients with abdominal malignancy after remote jejunoileal bypass:
      surgical considerations decades later.

PMID- 24021300
TI  - Surgical critical care training for emergency physicians: curriculum
      recommendations.

PMID- 24021301
TI  - In vivo analgesic activity, toxicity and phytochemical screening of the
      hydroalcoholic extract from the leaves of Psidium cattleianum Sabine.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Psidium cattleianum Sabine is extensively used in
      Brazilian traditional medicine to treat several diseases including painful
      disorders. Aim of the study to investigate the toxicity and the possible
      analgesic activities of the hydroalcoholic extract from the leaves of Psidium
      cattleianum Sabine (ELPCS), to support its use in folk medicine. To screen the
      major phytochemical constituents of this extract and evaluate their antioxidant
      activity. MATERIALS AND METHODS: ELPCS was assessed for its antioxidant activity
      using the DPPH model. Its analgesic activity was examined using mouse models of
      acetic acid-induced writhing and hot plate paw licking models. The major
      phytochemical constituents of the extract were screened; their toxicity on LLC
      MK2 mammalian cells was evaluated. RESULTS: ELPCS exhibited significant
      peripheral analgesic activity at doses of 60, 80, 100, 200 and 400mg/kg in mice,
      but it did not display central analgesic activity and not was toxic to LLC-MK2
      cell (LD50>400 ug/mL). The extract exhibited free radical scavenging activity as
      evidenced by IC50 values (15.9 ug/mL) obtained by the DPPH method. Phytochemical
      screening detected flavonoids, saponins, cardiac glycosides, anthraquinones, and
      tannins. CONCLUSIONS: The results of the experimental studies proved the
      analgesic activity of ELPCS and supported the traditional use of this plant.

PMID- 24021302
TI  - kLa of stirred tank bioreactors revisited.
AB  - By means of improved feedback control kLa measurements become possible at a
      precision and reproducibility that now allow a closer look at the influences of
      power input and aeration rate on the oxygen mass transfer. These measurements are
      performed online during running fermentations without a notable impact on the
      biochemical conversion processes. A closer inspection of the mass transfer during
      cultivations showed that at least the number of impellers influences mass
      transfer and mixing: On the laboratory scale, two hollow blade impellers clearly
      showed a larger kLa than the usually employed three impeller versions when
      operated at the same agitation power and aeration rate. Hollow blade impellers
      are preferable under most operational conditions because of their perfect gas
      handling capacity. Mixing time studies showed that these two impeller systems are
      also preferable with respect to mixing. Furthermore the widths of the baffle bars
      depict a significant influence on the kLa. All this clearly supports the fact
      that it is not only the integral power density that finally determines kLa. 

PMID- 24021303
TI  - An open-label, single arm, phase III clinical study to evaluate the efficacy and
      safety of CJ smallpox vaccine in previously vaccinated healthy adults.
AB  - BACKGROUND: The increased possibility of bioterrorism has led to reinitiation of
      smallpox vaccination. In Korea, more than 30 years have passed since the last
      smallpox vaccinations, and even people who were previously vaccinated are not
      regarded as adequately protected against smallpox. We evaluated the efficacy and
      safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in
      healthy adults previously vaccinated against smallpox. METHODS: We conducted an
      open label, single arm, phase III clinical trial to evaluate the efficacy and
      safety of CJ-50300. Healthy volunteers, previously vaccinated against smallpox,
      born between 1950 and 1978 were enrolled. CJ-50300 was administered with a
      bifurcated needle over the deltoid muscle according to the recommended method.
      The rate of the cutaneous take reaction, humoral immunogenicity, and safety of
      the vaccine was assessed. RESULTS: Of 145 individuals enrolled for vaccination,
      139 completed the study. The overall rates of cutaneous take reactions and
      humoral immunogenicity were 95.0% (132/139) and 88.5% (123/139), respectively.
      Although 95.9% (139/145) reported adverse events related to vaccination, no
      serious adverse reactions were observed. CONCLUSION: CJ-50300 can be used safely
      and effectively in healthy adults previously vaccinated against smallpox.

PMID- 24021304
TI  - Assessment of causality of individual adverse events following immunization
      (AEFI): a WHO tool for global use.
AB  - Serious illnesses or even deaths may rarely occur after childhood vaccinations.
      Public health programs are faced with great challenges to establish if the events
      presenting after the administration of a vaccine are due to other conditions, and
      hence a coincidental presentation, rather than caused by the administered
      vaccines. Given its priority, the Global Advisory Committee for Vaccine Safety
      (GACVS) commissioned a group of experts to review the previously published World
      Health Organization (WHO) Adverse Event Following Immunization (AEFI) causality
      assessment methodology and aide-memoire, and to develop a standardized and user
      friendly tool to assist health care personnel in the processing and
      interpretation of data on individual events, and to assess the causality after
      AEFIs. We describe a tool developed for causality assessment of individual AEFIs
      that includes: (a) an eligibility component for the assessment that reviews the
      diagnosis associated with the event and identifies the administered vaccines; (b)
      a checklist that systematically guides users to gather available information to
      feed a decision algorithm; and (c) a decision support algorithm that assists the
      assessors to come to a classification of the individual AEFI. Final
      classification generated by the process includes four categories in which the
      event is either: (1) consistent; (2) inconsistent; or (3) indeterminate with
      respect of causal association; or (4) unclassifiable. Subcategories are
      identified to assist assessors in resulting public health decisions that can be
      used for action. This proposed tool should support the classification of AEFI
      cases in a standardized, transparent manner and to collect essential information
      during AEFI investigation. The algorithm should provide countries and health
      officials at the global level with an instrument to respond to vaccine safety
      alerts, and support the education, research and policy decisions on immunization
      safety. 

PMID- 24021305
TI  - Seroprevalences of varicella-zoster virus, herpes simplex virus and
      cytomegalovirus in a cross-sectional study in Mexico.
AB  - We estimated the seroprevalences of varicella-zoster virus (VZV), herpes simplex
      virus (HSV) and cytomegalovirus (CMV) in this cross-sectional database study.
      Serum samples collected during the National Health and Nutrition survey (ENSANUT
      2006) were obtained from subjects aged 1-70 years between January and October
      2010. Serological assays for the determination of antibodies against VZV, HSV and
      CMV were performed. The overall seroprevalences of VZV, HSV-1, HSV-2 and CMV were
      85.8%, 80.9%, 9.9% and 89.2%, respectively. Seroprevalences of VZV, HSV-1 and CMV
      were comparable between males and females. For HSV-2, although the seroprevalence
      rate was higher in females when compared to males, this difference in
      seroprevalence was not statistically significant. Seroprevalence rates for VZV,
      HSV-1, HSV-2 and CMV increased with age (p-value<.0001). Differences in
      seroprevalence rate for VZV by socioeconomic status (SES) were significant (p
      value<0001). Results of the serological analyses reported high VZV
      seroprevalence, indicating high transmission in the Mexican population with
      children and adolescents at risk of acquiring VZV. Global HSV-1 seroprevalence
      was high, especially in adults. HSV-1 and HSV-2 seroprevalences were consistently
      higher in women than men, particularly for HSV-2. CMV seroprevalence was higher
      in Mexico when compared to developed countries. Seroepidemiological data on VZV
      supports the fact that varicella vaccination may serve as an alternative
      effective solution to reduce transmission in the Mexican population. For CMV and
      HSV, since no vaccines are available, activities to reduce transmission are
      important to reduce the risk of complications and therefore need to be
      considered. 

PMID- 24021307
TI  - Paediatric asthma and pneumococcal vaccination.
AB  - Asthma is a clinical condition that has only recently been considered a risk
      factor for the development of pneumococcal infections. In the most recent
      guidelines concerning the use of pneumococcal vaccines, the Advisory Committee on
      Immunisation Practices recommends pneumococcal vaccination only when children
      with asthma aged <71 months are treated with high-dose corticosteroids, whereas
      the same Committee clearly indicates that asthma (without any definition of
      severity or treatment) is a reason for systematic pneumococcal vaccination in
      adults. It is also unclear which pneumococcal vaccine should be used and how to
      face the problem of booster doses. The main aim of this paper is to describe what
      is known about the real risk of pneumococcal infections in children with asthma,
      and discuss the unsolved problems regarding the paediatric use of pneumococcal
      vaccines. There are few published data regarding pneumococcal colonisation and
      the burden of pneumococcal disease in asthmatic children and adolescents, and
      none at all concerning the relationship between paediatric asthma and immune
      responses to pneumococcal vaccines. Further studies are therefore essential to
      assure that children and adolescents with asthma receive the best protection
      against pneumococcal diseases. 

PMID- 24021306
TI  - Willingness to participate in HIV vaccine efficacy trials among high risk men and
      women from fishing communities along Lake Victoria in Uganda.
AB  - INTRODUCTION: HIV vaccine efficacy trials conducted in suitable populations are
      anticipated in sub-Saharan Africa. We assessed the willingness to participate in
      future vaccine trials among individuals from fishing communities along Lake
      Victoria, Uganda. METHODS: From July to October 2012, we described a hypothetical
      vaccine trial to 328 (62.2% men) adults (18-49 years), at risk of HIV infection
      within 6 months of enrolment in a cohort and assessed their willingness to
      participate in the trial. Chi-square and logistic regression models were fitted
      to assess associations between vaccine trial attributes, participants'
      characteristics and willingness to participate. RESULTS: Overall, 99.4% expressed
      willingness to participate in the hypothetical HIV vaccine trial. This decreased
      marginally with introduction of particular vaccine trial attributes. Delaying
      pregnancy for 10 months and large blood draw had the largest effects on reducing
      willingness to participate to 93.5% (p=0.02) and 94.5% (p=0.01) respectively. All
      the vaccine trial attributes in combination reduced willingness to participate to
      90.6%. This overall reduction in willingness to participate was significantly
      associated with gender and exchange of gifts for sex in multivariable analysis;
      women were more than three times as likely to have expressed unwillingness to
      participate in future vaccine trials as men (aOR=3.4, 95% CI: 1.55, 7.33) and
      participants who never received gifts in exchange for sex were more than four
      times as likely to have expressed unwillingness as those who received gifts for
      sex (aOR=4.5; 95%CI 1.30, 16.70). The main motivators of participation were
      access to HIV counselling and testing services (31.9%), HIV education (18.0%),
      hope of being prevented from acquiring HIV (16.6%) and health care (12.5%).
      CONCLUSION: Our study identifies an important population for inclusion in future
      HIV prevention trials and provides important insights into acceptability of trial
      procedures, differences in decisions of women and men and areas for further
      participant education.

PMID- 24021308
TI  - Bovine serum albumin nanoparticle vaccine reduces lung pathology induced by live
      Pseudomonas aeruginosa infection in mice.
AB  - Pseudomonas aeruginosa is an important opportunistic human pathogen that causes
      severe infections in immunocompromised patients and also in cystic fibrosis
      patients. The aim of this work was to study if a bovine serum albumin
      nanoparticles with entrapped antigens extracted from P. aeruginosa would be able
      to protect mice from nasal infection by this pathogen. Mice were immunized via
      the subcutaneous route using P. aeruginosa antigens, empty nanoparticles or
      nanoparticles with entrapped P. aeruginosa antigens on days 0, 7 and 14. The
      total IgG antibody production and specific IgG1 and IgG2a titer were measured by
      ELISA. Immunized mice were challenged with live P. aeruginosa and their lungs
      were collected for histopathology studies. Our data showed that NPPa-vaccinated
      mice presented a high anti-Pseudomonas IgG1 and a low IgG2a antibody titles and
      decreased inflammatory signs, with significant reduction in intensity and
      concentration of inflammatory cells, lower hemorrhagic, edema and hyperemia signs
      in the lungs of challenge mice with live P. aeruginosa if compared to the other
      groups. Therefore, this formulation is able to induce a functional response in an
      animal model of infection and thereby is a promising platform for P. aeruginosa
      vaccines. 

PMID- 24021309
TI  - Humoral response and antiviral cytokine expression following vaccination of
      thoroughbred weanlings--a blinded comparison of commercially available vaccines.
AB  - Previous studies in experimental ponies using interferon gamma (IFN-gamma) as a
      marker for cell mediated immune (CMI) response demonstrated an increase in IFN
      gamma gene expression following vaccination with an ISCOM subunit, a canarypox
      recombinant and more recently, an inactivated whole virus vaccine. The objective
      of this study was to carry out an independent comparison of both humoral antibody
      and CMI responses elicited following vaccination with all these vaccine
      presentation systems. Antibody response of 44 Thoroughbred weanlings was
      monitored for three weeks following the second dose of primary vaccination (V2)
      by single radial haemolysis (SRH). The pattern of antibody response was similar
      for all vaccines. The antibody response of horses vaccinated with the inactivated
      whole virus vaccine (Duvaxyn IE-T Plus) was superior to that of the horses
      vaccinated with the ISCOM-matrix subunit (Equilis Prequenza Te) and canarypox
      recombinant (ProteqFlu-Te) vaccine. In this study 39% of weanlings failed to
      seroconvert following their first dose of primary vaccination (V1). Poor response
      to vaccination (H3N8) was observed among weanlings vaccinated with Equilis
      Prequenza Te and ProteqFlu-Te but not among those vaccinated with Duvaxyn IE-T
      Plus. PAXgene bloods were collected on days 0, 2, 7 and 14 following V1. Gene
      expression levels of IFN-gamma, IL-1beta (proinflammatory cytokine) and IL-4 (B
      cell stimulating cytokine) were measured using RT-PCR. Mean gene expression
      levels of IL-1beta and IL-4 peaked on day 14 post vaccination. The increase in IL
      4 gene expression by horses vaccinated with Equilis Prequenza Te was
      significantly greater to those vaccinated with the other two products.
      Vaccination with all three vaccines resulted in a significant increase in IFN
      gamma gene expression which peaked at 7 days post V1. Overall, there was no
      significant difference in IFN-gamma gene expression by the horses vaccinated with
      the whole inactivated, the subunit and the canarypox recombinant vaccines
      included in this study. 

PMID- 24021310
TI  - A passive cold storage device economic model to evaluate selected immunization
      location scenarios.
AB  - BACKGROUND: The challenge of keeping vaccines cold at health posts given the
      unreliability of power sources in many low- and middle-income countries and the
      expense and maintenance requirements of solar refrigerators has motivated the
      development of passive cold storage devices (PCDs), containers that keep vaccines
      cold without using an active energy source. With different PCDs under
      development, manufacturers, policymakers and funders need guidance on how varying
      different PCD characteristics may affect the devices' cost and utility. METHODS:
      We developed an economic spreadsheet model representing the lowest two levels of
      a typical Expanded Program on Immunization (EPI) vaccine supply chain: a district
      store, the immunization locations that the district store serves, and the
      transport vehicles that operate between the district store and the immunization
      locations. The model compares the use of three vaccine storage device options
      [(1) portable PCDs, (2) stationary PCDs, or (3) solar refrigerators] and allows
      the user to vary different device (e.g., size and cost) and scenario
      characteristics (e.g., catchment area population size and vaccine schedule).
      RESULTS: For a sample set of select scenarios and equipment specification, we
      found the portable PCD to generally be better suited to populations of 5,000 or
      less. The stationary PCD replenished once per month can be a robust design
      especially with a 35L capacity and a cost of $2,500 or less. The solar device was
      generally a reasonable alternative for most of the scenarios explored if the cost
      was $2,100 or less (including installation). No one device type dominated over
      all explored circumstances. Therefore, the best device may vary from country-to
      country and location-to-location within a country. CONCLUSIONS: This study
      introduces a quantitative model to help guide PCD development. Although our
      selected set of explored scenarios and device designs was not exhaustive, future
      explorations can further alter model input values to represent additional
      scenarios and device designs.

PMID- 24021311
TI  - Bluetongue virus with mutated genome segment 10 to differentiate infected from
      vaccinated animals: a genetic DIVA approach.
AB  - Bluetongue virus (BTV) includes 24 serotypes and recently even more serotypes are
      proposed. Mass vaccination campaigns highlight the need for differential
      diagnostics in vaccinated populations. Bluetongue disease is routinely diagnosed
      by serological and virological tests by which differentiation infected from
      vaccinated animals (DIVA principle) is not possible. Real time PCR tests
      preferably detect all BTV serotypes (panBTV PCR tests). These PCR tests operate
      as frontline test to detect new BTV incursions. However, highly sensitive panBTV
      PCR tests can also detect currently applied inactivated and modified-live
      vaccines. Here, BTV with eight silent mutations in segment 10 (Seg-10) was
      generated by reverse genetics. This BTV mutant is not detected by a Seg-10 panBTV
      PCR test (genetic DIVA). Thus, inactivated BT vaccine with this mutated Seg-10
      will avoid false positive PCR results post vaccination, whereas BTV infected
      animals can be positively diagnosed with the accompanying Seg-10 panBTV PCR test
      (DIVA-test) far beyond the infectious period. 

PMID- 24021312
TI  - Oral immunization of fish against iridovirus infection using recombinant antigen
      produced from rice callus.
AB  - Fish iridoviruses cause systemic diseases with high morbidity and mortality in
      various species of wild and farm-raised fish, resulting in severe economic
      losses, and no large-scale protective vaccine program or therapy is currently
      available. In this study, we expressed a recombinant major capsid protein (rMCP)
      of rock bream iridovirus in transgenic rice callus. The rMCP in lyophilized rice
      callus powder was added to feed to induce intestinal mucosal immunity for
      protection against and/or to reduce the severity of the iridovirus infection. We
      found that fish (Rock bream) immunized orally with rMCP underwent successful
      induction of antibodies (P<0.05) and were protected (P<0.001) against viral
      challenge. These results suggest that oral administration of rMCP as an antigen
      is a useful method to implement a vaccine program against iridovirus and other
      marine viral diseases. 

PMID- 24021313
TI  - Safety and immunogenicity of three tetravalent dengue vaccine formulations in
      healthy adults in the USA.
AB  - BACKGROUND: A candidate recombinant, live-attenuated, CYD tetravalent dengue
      vaccine (CYD-TDV) has recently demonstrated immunogenicity, efficacy and good
      tolerability. This study was performed to evaluate three CYD-TDV formulations in
      adults. METHODS: This was a randomized, double-blind, multicenter, phase II
      trial. The vaccine formulations were: CYD-TDV 5555 (~5log10 tissue culture
      infectious dose 50% [TCID50] of serotypes 1-4); CYD-TDV 5553 (~5log10 TCID50 of
      serotypes 1-3 and ~3log10 TCID50 of serotype 4); and CYD-TDV 4444 (~4log10 TCID50
      of serotypes 1-4). Vaccinations were administered at 0, 6 and 12 months.
      Immunogenicity was assessed using the plaque reduction neutralization test.
      RESULTS: In total, 260 individuals were enrolled. The 5555 formulation elicited a
      superior serotype 4 response versus the 5553 formulation, with seropositivity
      rates of 89.7% and 58.3%, respectively, after the second dose (between-group
      difference 31.4%; 95% confidence interval 18.2-43.2). After each of the three
      doses, seropositivity rates for serotypes 1-3 were numerically highest with CYD
      TDV 5553 and lowest with the 4444 formulation; seropositivity rates for serotype
      4 were similar with the 5555 and 4444 formulations, and much lower among
      recipients of CYD-TDV 5553. Geometric mean titers followed the same pattern as
      that seen with seropositivity rates. Safety/reactogenicity results were similar
      for all three vaccine formulations, although the percentage of participants
      reporting solicited injection site reactions was lower with CYD-TDV 4444 than
      with the other two formulations. All serious adverse events were unrelated to
      vaccination. CONCLUSIONS: Reducing the dose of serotype 4 antigen (5553
      formulation) creates an imbalance in the immune response to CYD-TDV. Immune
      responses to CYD-TDV 5555 were slightly higher than to the 4444 formulation.
      Development of CYD-TDV 5555 has subsequently been pursued.

PMID- 24021314
TI  - Application of real-time quantitative polymerase chain reaction to monitoring
      infection of classic swine fever virus and determining optimal harvest time in
      large-scale production.
AB  - Due to the non-cytopathogenic replication of classical swine fever virus (CSFV)
      in cell culture, large-scale production of CSFV using bioreactor system remains
      the problem of monitoring the time of maximum virus production for optimal
      harvest. In this study, we proposed the application of real-time quantitative PCR
      assay to monitoring the progress of CSFV infection and yield determination in
      large scale. The region of NS5B of CSFV responsible for CSFV genome replication
      was used for the designation of primers and probe. Viral titers determined by the
      real-time quantitative PCR assay were compared with the conventional cell-culture
      based method of immunofluorescent staining. Results from large scale production
      show that a similar profile of CSFV production was successfully outlined by real
      time quantitative PCR and virus yields were comparable to the results from
      immunofluorescent staining assay. By using this method, an optimal harvesting
      time of the production could be rapidly and precisely determined leading to an
      improvement in virus harvest. 

PMID- 24021315
TI  - Seroprevalence of rubella in the cord blood of pregnant women and congenital
      rubella incidence in Nha Trang, Vietnam.
AB  - To investigate susceptibility to and factors associated with rubella infection
      among pregnant mothers and to estimate the burden of congenital rubella infection
      (CRI) in Vietnam where rubella-containing vaccine (RCV) is not included in the
      routine immunization program, we conducted a prospective cohort study in Nha
      Trang, Vietnam between 2009 and 2010. Rubella-specific immunoglobulin-M and
      immunoglobulin-G were investigated in cord blood samples by enzyme immunoassay.
      Corresponding clinical-epidemiological data were analyzed and the national
      congenital rubella syndrome (CRS) incidence was estimated using modeling. We
      enrolled 1988 pairs of mothers aged 17-45 years and their newborn babies. No
      mothers had received RCV. Multivariate analysis revealed that mothers aged 17-24
      (aOR 2.5, 95% CI: 1.7-3.8) or 25-34 (1.4, 1.0-2.1) years were more likely to be
      susceptible than those aged 35-45 years. Overall 28.9% (574/1988, 95% CI: 26.9
      30.9%) of mothers were seronegative. The CRI rate was 151 (95% CI: 0-322) per
      100,000 live births. Modeling estimated that 3788 babies (95% CI: 3283-4143) were
      born with CRS annually in Vietnam with an overall CRS incidence of 234 (95% CI:
      207-262) cases per 100,000 live births. A substantial proportion of women of
      childbearing age (WCBA) are at risk of rubella infection during pregnancy and
      this can result in a high frequency of miscarriage or burden of CRS across
      Vietnam. Prompt introduction of RCV into national immunization program with catch
      up vaccination to children and WCBA will reduce CRI in Vietnam. 

PMID- 24021316
TI  - Biomarkers of Alzheimer's disease: the present and the future.
AB  - A paradigm shift has occurred in the last ten years in the diagnostic field of
      Alzheimer's disease (AD). Scientific thought has enriched the concept of AD as a
      pathophysiological continuum and emphasized contribution of biological,
      morphological and functional brain imaging biomarkers for diagnosis, in
      particular during the early stages of the disease. We address here the present
      and the future of these biological biomarkers. Most of them are linked to the
      pathophysiological lesions of the Alzheimer process: aggregates of
      hyperphosphorylated tau proteins, also called neurofibrillary tangles (NFT), and
      extracellular deposit of amyloid-beta peptides (Abeta), also called senile
      plaques. The detection in the cerebrospinal fluid (CSF) of tau and Abeta
      represents the current diagnostic practice of AD. Improvement for a more accurate
      and earlier biological diagnosis is however expected using a new generation of
      biomarkers, mostly in relation with tau and Abeta metabolism. 

PMID- 24021317
TI  - Muscle diseases with prominent joint contractures: Main entities and diagnostic
      strategy.
AB  - Muscle diseases may have various clinical manifestations including muscle
      weakness, atrophy or hypertrophy and joint contractures. A spectrum of non
      muscular manifestations (cardiac, respiratory, cutaneous, central and peripheral
      nervous system) may be associated. Few of these features are specific. Limb joint
      contractures or spine rigidity, when prevailing over muscle weakness in ambulant
      patients, are of high diagnostic value for diagnosis orientation. Within this
      context, among several disorders, four groups of diseases should systematically
      come to mind including the collagen VI-related myopathies, the Emery-Dreifuss
      muscular dystrophies, the SEPN1 and FHL1 related myopathies. More rarely other
      genetic or acquired myopathies may present with marked contractures. Diagnostic
      work-up should include a comprehensive assessment including family history,
      neurological, cardiologic and respiratory evaluations. Paraclinical
      investigations should minimally include muscle imaging and electromyography.
      Muscle and skin biopsies as well as protein and molecular analyses usually help
      to reach a precise diagnosis. We will first describe the main muscle and
      neuromuscular junction diseases where contractures are typically a prominent
      symptom of high diagnostic value for diagnosis orientation. In the following
      chapters, we will present clues for the diagnostic strategy and the main measures
      to be taken when, at the end of the diagnostic work-up, no definite muscular
      disease has been identified.

PMID- 24021318
TI  - Double intussusceptions with small intestinal adenoma in pregnancy.

PMID- 24021319
TI  - Expression of integrin beta3 and osteopontin in the eutopic endometrium of
      adenomyosis during the implantation window.
AB  - OBJECTIVE: To investigate the expression of integrin beta3 and osteopontin (OPN)
      in the eutopic endometrium of adenomyosis and to characterize possible
      endometrial defects in adenomyosis. STUDY DESIGN: Twenty-eight adenomyosis
      patients and 27 control fertile women were involved in this study. Endometrial
      samples were collected during the implantation window. Integrin beta3 subunits
      and OPN in the adenomyosis and control endometria were assessed by
      immunohistochemical staining and quantitative real-time polymerase chain
      reaction. A one-tailed t-test and a non-parametric Mann-Whitney U-test were used
      to test significance. RESULTS: The mRNA and immunostaining intensity of integrin
      beta3 and OPN were significantly lower in the adenomyosis patients than in the
      controls. CONCLUSIONS: Abnormal expression of integrin beta3 and OPN in the
      endometrium of adenomyosis may contribute to infertility in some patients.

PMID- 24021320
TI  - Appraising journals--impact factor, citation index, ...?

PMID- 24021321
TI  - Applicability of regression equation using widths of mandibular permanent first
      molars and incisors as a predictor of widths of mandibular canines and premolars
      in contemporary Indian population.
AB  - BACKGROUND: Predicting the size of unerupted teeth during the mixed dentition
      period is a critical factor in managing the developing occlusion. Different
      studies found that the combined width of only the four mandibular permanent
      incisors is not a good predictor of the sum of unerupted mandibular permanent
      canines and premolars (SPCP). In 2007, Melgaco et al. developed a new method for
      SPCP by measuring the sum of the mandibular first permanent molars and four
      mandibular permanent incisors (SMI). AIM: It was aimed to evaluate the accuracy
      of this new method in comparison with Moyers' mixed dentition analysis table in
      contemporary Indian population. SETTINGS AND DESIGN: Sixty boys and 60 girls from
      Gandhinagar district (age ranged from 12 to 14 years) were included. MATERIALS
      AND METHODS: The mesiodistal crown widths of all fully erupted teeth were
      measured with digital vernier callipers and the odontometric values obtained were
      then subjected to statistical and linear regression analysis. RESULTS: Student's
      unpaired t-test gave statistically significant difference between the original
      values of teeth and the values obtained by Melgaco's prediction equation as well
      as Moyers' mixed dentition analysis table (P < 0.001). High values of correlation
      (r = 0.77) and determination coefficients (r2 = 0.59) were found while
      considering Melgaco's method. Also, no statistically significant difference was
      found between the tooth sizes of males and females. CONCLUSION: From this study,
      it can be evaluated that Melgaco's method gives better prediction and a
      simplified equation Y = 0.925X can be suggested for the present population.

PMID- 24021322
TI  - A comparison of oral hygiene status and dental caries experience among
      institutionalized visually impaired and hearing impaired children of age between
      7 and 17 years in central India.
AB  - AIM: The aim of this study is to compare the oral hygiene status and dental
      caries experience among institutionalized visually impaired and hearing impaired
      children of age between 7 and 17 years in Bhopal city of Madhya Pradesh located
      in Central India. MATERIALS AND METHODS: A total of 95 hearing impaired and 48
      visually impaired children of age between 7 and 17 years were recruited from
      special care institutions (one institution of hearing impaired and two
      institutions of visually impaired) in Bhopal city. Information related to
      different study variables was obtained from both groups. Oral hygiene index
      simplified (OHI[S]), decayed,extracted, filled teeth (deft and DECAYED, MISSING,
      FILLED TETTH (DMFT)) indices were used to record the oral hygiene status and
      dental caries experience. RESULTS: Mean OHI(S) score for hearing impaired was
      1.15 +/- 0.72 while it was 1.51 +/- 0.93 for visually impaired children (P <
      0.05). Mean DMFT score was 1.4 +/- 1.95 and 0.94 +/- 1.45 among hearing impaired
      and visually impaired respectively. The hearing impaired had a mean deft score of
      0.47 +/- 1.01 and in visually impaired it was 0.19 +/- 0.79 and the difference
      was statistically significant (P < 0.05). CONCLUSION: Oral hygiene status of
      hearing impaired children was better than visually impaired and the difference
      was statistically significant. There was no significant difference between both
      groups with respect to DMFT. The hearing impaired children had significantly
      higher deft than visually impaired.

PMID- 24021323
TI  - Liquorice root extracts as potent cariostatic agents in pediatric practice.
AB  - OBJECTIVE: The present study was designed to evaluate the in vitro as well as in
      vivo cariostatic efficacy of aqueous and ethanolic extracts of liquorice and
      assess their acceptability among child patients. MATERIALS AND METHODS: Minimum
      bactericidal concentrations of aqueous and ethanolic extracts of liquorice
      against mutans streptococci were evaluated and their toxicity profiles were
      tested using the model organism Caenorhabditis elegans. The clinical trial was
      conducted as a double-blind pilot study where pediatric patients (N = 60), aged 7
      14 years, were equally divided by randomization into three groups, namely, Group
      1 using aqueous liquorice mouthwash (15%), Group 2 using ethanolic liquorice
      mouthwash (3.75%), and Group 3 using chlorhexidine gluconate (0.156%) as positive
      control. A baseline pre-rinse and three post-rinse saliva samples were evaluated
      for the changes in pH and mutans streptococci colony counts. Palatability of
      liquorice extracts was assessed through a self-designed questionnaire having
      structured categorical responses. STATISTICAL ANALYSIS: Parametric evaluations
      were done using Analysis of Variance (ANOVA) and Dunnett's "t" test. RESULTS: The
      mean mutans streptococci colony counts in all three groups decreased
      significantly (P < 0.001) immediately after the oral rinsing. The reduction in
      colony counts was significant in ethanolic liquorice group as compared to the
      control (P < 0.01). Liquorice extracts also led to an immediate rise in salivary
      pH. The results showed an immediate antimicrobial action of liquorice extracts,
      with limited retentivity. CONCLUSION: The study affirms that both aqueous and
      ethanolic liquorice extracts are potent cariostatic agents and are found to be
      palatable by child patients.

PMID- 24021324
TI  - Evaluation of parents/guardian knowledge about the bruxism of their children:
      Family knowledge of bruxism.
AB  - BACKGROUND/AIM: Bruxism is the habitual, involuntary grinding or clenching of the
      teeth that affects both children and adults. The aim of the present study was to
      assess the level of knowledge parents/guardians have about the bruxism of their
      children. MATERIALS AND METHODS: A cross-sectional epidemiological study was
      developed for 221 parents/guardians of patients of the pediatric dentist in the
      Faculty of Dentistry of the Federal University of Minas Gerais (UFMG), Belo
      Horizonte, Brazil. A previously tested questionnaire, based on the criteria of
      the American Association of Sleep Medicine (AASM), was used to collect data from
      the participants in the waiting room of the clinics involved. Descriptive
      analysis was elaborated and the chi-squared test was applied (level of
      significance of 5%) using statistical software SPSS 17.0. RESULTS: The majority
      of the participants were mothers of the patients (84.2%). The mean age of the
      parents/guardians was 36.6 years. The mean age of children was 7.6 years. In
      total, 76.6% of the mothers, 40.2% of the fathers, and 48% of the children
      reported having bruxism. The participants believed that bruxism was associated
      with emotional factors (63.8%) and/or mystical factors (20.4%). The majority
      reported having sought help from doctors (54.4%), followed by mystics (20.4%) and
      dentists (19.1%). A statistically significant association was found between
      bruxism and children with restless sleep (P < 0.001) and in cases where both the
      parents and children were affected by bruxism (P < 0.001). CONCLUSION: Families
      require greater clarification regarding the factors that trigger bruxism.

PMID- 24021325
TI  - Comparative evaluation of retention ability of amorphous calcium phosphate
      containing and illuminating pit & fissure sealants in 6-9 year old age group.
AB  - AIMS: The primary aim of this study is to evaluate and to compare the retention
      of two different pit and fissure sealants on permanent mandibular 1 st molar
      teeth. MATERIALS AND METHODS: A total of 110 children aged between 6-9 years were
      selected. In each child, Aegis with amorphous calcium phosphate sealant was
      applied on the permanent mandibular 1 st molar of the right side while Delton the
      illuminating sealant was applied on the permanent mandibular 1 st molar of the
      left side, keeping the permanent maxillary 1 st molars as control. The treated
      teeth were evaluated for retention of sealants at 3, 6 and 12 months interval.
      STATISTICAL ANALYSIS USED: The statistical analysis was performed using the Mann
      Whitney U-test and Chi-square tests and Statistical Package for the Social
      Science version 15.0 statistical analysis software. RESULT: The results were
      showed that retention and loss of sealant from the occlusal surfaces of the
      sealed teeth in both groups was maximum between 3 and 6 months. CONCLUSION:
      Though statistically no significant difference was observed between the two
      groups, sealant with ACP showed better retention than the illuminating sealant.

PMID- 24021326
TI  - Reframing in dentistry: revisited.
AB  - The successful practice of dentistry involves a good combination of technical
      skills and soft skills. Soft skills or communication skills are not taught
      extensively in dental schools and it can be challenging to learn and at times in
      treating dental patients. Guiding the child's behavior in the dental operatory is
      one of the preliminary steps to be taken by the pediatric dentist and one who can
      successfully modify the behavior can definitely pave the way for a life time
      comprehensive oral care. This article is an attempt to revisit a simple behavior
      guidance technique, reframing and explain the possible psychological perspectives
      behind it for better use in the clinical practice. 

PMID- 24021327
TI  - Scanning electron microscope analysis of sealant penetration and adaptation in
      contaminated fissures.
AB  - OBJECTIVE: The objective of this study is to evaluate the penetration and
      adaptation of two different sealant materials applied under different conditions
      of contamination using scanning electron microscope (SEM) analysis. MATERIALS AND
      METHODS: A total of 56 extracted human third molar teeth were randomly assigned
      into eight equal groups. The treatment groups were defined by the combination of
      two sealant materials (glass ionomer fissure sealant "Fuji Triage" or resin-based
      fissure sealant "Clinpro TM") and four surface conditions (dry condition, water
      contamination, saliva contamination or saliva contamination and air-drying).
      Penetration depth, sealant adaptation and fissure types were evaluated under SEM
      after sectioning the teeth. Tukey's test and multiple linear regression analyses
      were used for statistical analysis. RESULTS: No significant difference in the
      sealant penetration and adaptation was found between both materials under dry
      conditions. However, under wet contaminations, resin-based sealant showed less
      adaptation and penetration with a significant difference when compared to glass
      ionomer sealant (P < 0.05). The multiple linear regression analyses revealed
      significant impact of different materials and types of contamination on the
      sealant penetration and adaptation. CONCLUSION: Glass ionomer sealant has better
      fissure penetration and more intimate adaptation than resin-based sealant under
      wet contamination conditions.

PMID- 24021328
TI  - The relationship between dental anxiety in children, adolescents and their
      parents at dental environment.
AB  - PURPOSE: The aim of the present study was to compare trait anxiety and dental
      anxiety among children, adolescents and their parents. MATERIALS AND METHODS: A
      cross-sectional study was conducted involving 100 patients from the Pediatric
      Dentistry Clinic of the Federal University of Parana (Brazil) between the ages of
      8 and 17 years (mean age: 10.3; standard deviation: 2.03) and their parents, who
      responded to Corah's Dental Anxiety Scale (DAS) and the Trait Anxiety Scale. The
      data were analyzed using the Mann-Whitney test, analysis of variance and both
      Pearson's and Spearman's correlation coefficients. RESULTS: Ninety percent of
      children and adolescents and 76% of the parents had moderate anxiety based on the
      DAS score. Seventy-four percent of children and adolescents and 72% of the
      parents had moderate anxiety based on the Trait Anxiety Scale score. The trait
      anxiety and dental anxiety scores were correlated among the adults (rs = 0.64)
      and children (r = 0.52), whereas no correlation between scores was found among
      the adolescents. Associations were also found between children's trait anxiety
      and the dental and trait anxiety of their parents (both r = 0.43). CONCLUSIONS: A
      moderate degree of dental anxiety was prevalent among the children, adolescents
      and parents who took part in this investigation, with correlations demonstrated
      between some trait anxiety and dental anxiety scores.

PMID- 24021329
TI  - Hookah use among high school children in an Indian city.
AB  - CONTEXT: Use of hookah is on the rise among youngsters. A growing body of
      evidence suggests that these children are experimenting with this form of
      tobacco. AIMS: The study was carried out to know prevalence estimates of hookah
      use and factors associated with it among high school students. SETTINGS AND
      DESIGN: This study adds to the current literature by providing prevalence
      estimates and factors associated with hookah use among high school students of
      Indore - a city in central India. MATERIALS AND METHODS: A cross-sectional survey
      of 1000 students from high schools was conducted to find hookah users and factors
      associated with its use. RESULTS: Hookah users in this study population were
      7.6%. Most of them first learned about hookah from friends (63.2%). They usually
      smoked in hookah lounges (85.5%). These children believed that hookah was safer
      and more socially acceptable than cigarettes. CONCLUSIONS: Misperceptions of
      safety and popularity of hookah among the younger generation are cause for
      concern. Presence of hookah lounges should be a target for further regulation.
      Prevention activities are necessary to prevent this rising public health concern.

PMID- 24021330
TI  - Freeman-Sheldon syndrome: a dental perspective.
AB  - Freeman-Sheldon syndrome is a rare progressive myopathic disorder affecting the
      face, chest, and limbs. It is characterized by three basic abnormalities:
      microstomia with pouting lips, camptodactyly with ulnar deviation of the fingers,
      and talipes equinovarus. Presence of microstomia is always associated with
      practical difficulties of oral hygiene maintenance and increased susceptibility
      to caries. Patient as well as parental counseling is important in these cases.
      This case report presents a 7-year-old child with Freeman-Sheldon syndrome.
      Emphasis is given for the dental management of such children. 

PMID- 24021331
TI  - Kite string: an unusual mode of maxillofacial injury.
AB  - Kite flying is a popular sport among children. Most of the injuries sustained
      during kite flying are due to falls, cuts, head injuries, or fractures. Injury
      with innocent-looking kite string in the maxillofacial region is rare. A 41/2
      year-old male patient with a clean cut, deep incised wound exposing the fat and
      muscle was treated with primary closure. Kite flying is associated with injuries
      ranging from simple cuts to grave lacerations or head trauma. The severity of
      lacerations depends on the abrasive material that is often placed on the string
      of the kite to increase its ability to cut. Injuries related to kite flying are
      preventable. Preventive measures include choosing a safe location and the need
      for increasing awareness about the possible effects of such a sport. 

PMID- 24021333
TI  - Custom-made ocular prosthesis for a pediatric patient with unilateral
      anopthalmia: a case report.
AB  - Congenitally missing eye, often called as anopthalmia, is a rare condition. This
      causes disfigurement of the face, which poses psychological effect on children,
      making them emotionally weak and conscious which, in turn, causes anxiety,
      stress, and depression at an early age in life. The custom-made ocular prostheses
      should thus be provided as soon as possible to help children improve their social
      acceptance. We present a case of 9-year-old boy who reported with congenital
      anopthalmia of right eye, which was then restored with custom-made ocular
      prosthesis. 

PMID- 24021332
TI  - Radicular cyst followed by incomplete pulp therapy in primary molar: a case
      report.
AB  - Radicular cysts are one of the most common odontogenic cyst of the jaws. However,
      those arising from primary teeth are rare. An 8-year-old boy reported to the
      Department of Pedodontics and Preventive Dentistry with the chief complaint of
      pain and swelling on the lower left primary molar tooth region. Radiographic
      examination revealed a well-defined radiolucency with continuous hyperostotic
      border. Considering the age of the child, size of lesion, and involvement of
      unerupted premolars; marsupialization was preferred as a conservative treatment
      of choice. The success of the treatment was evident both clinically and
      radiographically during the follow-up period. 

PMID- 24021334
TI  - Erosive oral lichen planus with cutaneous involvement in a 7-year-old girl: a
      rare case report.
AB  - Lichen planus is a chronic autoimmune, mucocutaneous disease, which can affect
      the oral mucosa, skin, genital mucosa, scalp and nails, and commonly seen in
      adults. Childhood lichen planus is a rare entity, which is characterized by skin
      lesions with the oral involvement being extremely uncommon. There are only a few
      reports on this subject in the literature. Early and correct diagnosis with
      adequate management is very important to avoid further complications as it is a
      pre-malignant condition. Herewith, we report a seven-year-old girl having erosive
      oral lichen planus with cutaneous involvement, which responded well to the
      treatment. This is to add another case of lichen planus in a child and to
      emphasize its consideration in the differential diagnosis of oral mucosal red and
      white lesions in children. 

PMID- 24021335
TI  - Delayed replantation of an avulsed maxillary premolar with open apex: a 24 months
      follow-up case report.
AB  - Avulsion of permanent teeth is most serious of all dental injuries and accounts
      for 1-16% of all traumatic injuries, of which maxillary incisors are most
      commonly involved. However, in this report a rare case of isolated avulsed
      immature premolar has been described. The patient had reported more than 3 hours
      after the trauma with a tooth stored in dry condition and soil contamination. The
      prognosis depends on measures taken at the place of accident or the time
      immediately after avulsion. Replantation is the treatment of choice, but cannot
      always be performed immediately. An appropriate emergency management and
      treatment plan is important for good prognosis. In this report stepwise
      management of an avulsed immature maxillary premolar with extended period of dry
      storage has been described followed up for a period of 2 yrs. 

PMID- 24021336
TI  - Intentional extraction and replantation: the last resort.
AB  - The importance of the first molar in the development of occlusion is well-known.
      The difficulties when first molar is not there during the eruption of the second
      molar and the premolar don't have to be explained much. The construction of a
      space maintainer in the area of missing first molar is difficult when seven and
      five are not erupted. The article highlights a case where a grossly decayed first
      molar with repeated endodontic failures was treated by intentional extraction and
      replantation as a last resort. A follow-up along with indications and
      considerations are documented. 

PMID- 24021337
TI  - Dentigerous cyst in a young child: clinical insight and a case report.
AB  - A dentigerous cyst or follicular cyst is an odontogenic cyst - thought to be of
      developmental origin - associated with the crown of an unerupted tooth. Such cyst
      remain initially completely asymptomatic unless when infected. The purpose of
      this case report was to describe the diagnosis and management of dentigerous cyst
      in a 9-year-old boy. The chosen treatment was cyst enucleation and tooth
      extraction. 

PMID- 24021338
TI  - Seroepidemiology of dengue in travellers.

PMID- 24021339
TI  - Microvascular findings in patients with systemic lupus erythematosus assessed by
      fundus photography with fluorescein angiography.
AB  - OBJECTIVES: Although a series of trials support systemic lupus erythematosus
      (SLE) is associated with increased atherosclerosis and cardiovascular events, the
      link between microvascular structural change and the disease activity of SLE is
      not defined. We measured retinal microvasculature change by fundus photography
      with fluorescein angiography (FAG) and investigated the association between
      retinal vasculature and clinical parameters of SLE. METHODS: Fifty SLE patients
      and fifty healthy controls were included. Morphometric and quantitative features
      of the capillary image including retinal vascular sign and vessel diameters were
      measured with fundus photography and FAG. Information concerning SLE duration,
      cumulative dose of steroids and/or immunosuppressive drug intake was recorded,
      and autoantibodies were checked. SLE activity was assessed by SLE disease
      activity index (SLEDAI). RESULTS: The mean central retinal arteriolar equivalent
      (CRAE) was 89.7+/-14.5 MUm in SLE patients, showing narrower arteriole than that
      of controls (102.2+/-11.3 MUm). The mean central retinal venular equivalents
      (CRVE) was 127.7+/-14.8 MUm in SLE patients, also, narrower than that of controls
      (144.1+/-14.2 MUm), but both reached no statistical significance (p=0.154,
      p=0.609, respectively). Retinopathy was found in 26% of SLE patients. SLE
      patients with retinopathy were older than those without it, but reached no
      statistical significance. Disease duration, antidsDNA, and complement levels had
      no effect on the presence of retinopathy. SLE patients with retinopathy had a
      tendency to have higher cumulative steroid doses, hsCRP and IgG aCL levels than
      those without retinopathy. With multiple regression analysis, hsCRP and IgG aCL
      were identified as contributing factors to the decreased CRAE, whereas no
      contributing factor was found to CRVE. CONCLUSIONS: Retinopathy and retinal
      arteriolar narrowing were more common in SLE patients, and retinal arteriolar
      diameter had significant correlation with hsCRP and IgG aCL levels. Retinal
      imaging is a comparative method for the assessment of microvascular findings of
      SLE patients.

PMID- 24021340
TI  - Transcription expression and clinical significance of mRNA of vascular
      endothelial growth factor and endostatin in liquid-based preparation specimens
      from patients with cervical dysplasia and carcinoma.
AB  - OBJECTIVES: The aim of this study was to assess the diagnostic usefulness of
      vascular endothelial growth factor (VEGF) and endostatin mRNA in cervical
      specimens of patients with cervical dysplasia and carcinoma. STUDY DESIGN:
      Transcription levels of VEGF and endostatin were detected by RT-PCR in cervical
      liquid-based preparation specimens and compared with cytological assessments.
      RESULTS: VEGF as well as endostatin mRNA expression was significantly associated
      with either cytological or histological diagnosis (p < 0.05). VEGF mRNA and
      endostatin mRNA were significantly more likely to be expressed in squamous cell
      carcinomas (SCC) than in cervical intraepithelial neoplasia (CIN) III (p < 0.01
      and p < 0.05), and obviously also more likely to be expressed in CINII than in
      CINI and in CINIII than in CINII (p < 0.05). Eleven inflammation lesions gave
      positive results by cytology but negative results by RT-PCR for VEGF and
      endostatin mRNA. Twenty-four SCC lesions gave false-negative or precancerous
      lesion results by cytology but positive results by RT-PCR for VEGF and/or
      endostatin mRNA expression. CONCLUSION: Transcription levels of VEGF and
      endostatin by RT-PCR may be an adjunct to cytology screening for early detection
      of cervical carcinomas and may determine the progressive potentiality of
      individual lesions, especially in high-risk patients.

PMID- 24021341
TI  - Smoking is a poor prognostic factor for male nasopharyngeal carcinoma treated
      with radiotherapy.
AB  - BACKGROUND AND PURPOSE: To evaluate the effect of smoking on prognosis of male
      nasopharyngeal carcinoma by comparing the treatment outcomes between smokers and
      non-smokers. MATERIALS AND METHODS: A total of 2450 nasopharyngeal carcinoma
      patients were enrolled, including 1865 male patients. Matching was performed
      between smokers and non-smokers in male patients according to age, UICC clinical
      stage, T stage, N stage and treatment. Survival outcomes were compared using
      Kaplan-Meier analysis and Cox regression. Smoking index was calculated by
      multiplying cigarette packs per day and smoked time (year). RESULTS: In male
      patients, smokers had significantly lower 5-year overall survival (70.1% vs.
      77.5%, P<0.001) and locoregional recurrent free survival (76.8% vs.82.4%, P =
      0.002) compared with non-smokers. Matched-pair analysis showed that smokers kept
      a high risk of death compared with non-smokers (HR = 2.316, P<0.001). High degree
      of smoking index (>15 pack-years) had a poor effect on overall survival (HR =
      1.225, P = 0.016). When smoking index was more than 45 and 60 pack-years, the
      risk for death increased to 1.498 and 1.899 fold compared with non-smokers (P =
      0.040, 0.001), respectively. CONCLUSIONS: Smoking was a poor prognostic factor
      for male nasopharyngeal carcinoma. The heavier the patients smoked, the poorer
      prognosis they suffered.

PMID- 24021342
TI  - Long-term quality-of-life after neoadjuvant short-course radiotherapy and long
      course radiochemotherapy for locally advanced rectal cancer.
AB  - PURPOSE: To evaluate long-term quality-of-life (QoL) after neoadjuvant short
      course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for
      locally advanced rectal cancer. METHODS: Between 1999 and 2008, 225 patients were
      treated with curative intent for locally advanced rectal cancer using neoadjuvant
      SC-RT (n=108) or LC-RCHT (n=117). SC-RT delivered 10 * 2.9 Gy twice daily with
      immediate surgery. LC-RCHT delivered 28 * 1.8 Gy concomitant with 5-FU based
      chemotherapy and delayed surgery. A cross-sectional QoL analysis was performed in
      disease-free patients using the EORTC-QLQ-C30 and EORTC-QLQ-CR29 questionnaires.
      RESULTS: After a median follow-up of 67 months, 133 patients were disease-free of
      which 120 (90%) returned the QoL questionnaires. Patients in the LC-RCHT cohort
      had a higher rate of uT4, uN+ and low tumor location. No difference in QoL was
      observed between SC-RT and LC-RCHT except an improved physical functioning in the
      LC-RCHT group (p=0.04). Comparing our total patient cohort with the general
      German population showed no difference in global health status but decreased QoL
      in several functional and bowel symptom scores. CONCLUSIONS: The finding of
      comparable long-term QoL after SC-RT and LC-RCHT adds to our knowledge of
      equivalent oncological outcome and may be useful in the decision making process
      between the two neoadjuvant approaches.

PMID- 24021343
TI  - p16INK4A, p53, EGFR expression and KRAS mutation status in squamous cell cancers
      of the anus: correlation with outcomes following chemo-radiotherapy.
AB  - BACKGROUND AND PURPOSE: Squamous cell carcinomas of the anal canal are associated
      with infection with Human Papilloma Viruses (HPVs). Chemo-radiotherapy (CRT)
      gives 70% 3-year relapse-free survival. Improved predictive markers and
      therapeutic options are required. METHODS: Tumours from 153 patients treated with
      radical chemo-radiotherapy (50.4 Gy in 28# with concurrent Mitomycin and 5
      Fluorouracil between 2004 and 2009) were retrieved and immunohistochemistry
      performed for p16(INK4A), p53 and EGFR and correlated with outcome. Primary and
      relapsed samples were analysed for mutations in KRAS. RESULTS: 137/153 (89.5%)
      stained moderately or strongly for p16(INK4A). p16(INK4A) correlated strongly
      with outcome. 37/137 patients demonstrating moderate/strong p16(INK4A) expression
      relapsed (27.0%), as opposed to 10/16 (62.5%) with absent/weak staining (log rank
      test p<0.001). p16 and p53 expression were inversely correlated. p16(INK4A)
      negative tumours were more frequent in men. p16(INK4A) negative patients had
      significantly worse overall survival (p<0.001). No mutations in KRAS were
      identified in primary tumours or relapses following treatment. CONCLUSIONS:
      p16(INK4A) is strongly associated with relapse in SCC of the anus and identifies
      patients with very poor rates of relapse-free and overall survival. Primary and
      recurrent anal cancer expresses wild type KRAS, unaffected by treatment,
      supporting trials targeting EGFR in poor risk/recurrent anal cancer.

PMID- 24021344
TI  - Reduction of the treated volume to involved node radiation therapy as part of
      combined modality treatment for early stage aggressive non-Hodgkin's lymphoma.
AB  - BACKGROUND AND PURPOSE: This retrospective study investigated whether focused
      involved node radiation therapy (INRT) can safely replace involved field RT
      (IFRT) in patients with early stage aggressive NHL. PATIENTS AND METHODS: We
      included 258 patients with stage I/II aggressive NHL who received combined
      modality treatment (87%) or primary RT alone (13%). RT consisted of a total dose
      of 30-40 Gy in 15-20 fractions IFRT or INRT. We compared survival, relapse
      pattern, radiation-related toxicity and quality of life for both RT techniques.
      RESULTS: Type of RT was not related to the outcome in either the uni- or
      multivariate survival analysis. Relapses developed in 59 of 252 patients (23%) of
      which 47 (80%) were documented as distant recurrence only. Failure of the INRT
      technique was noted in one patient. There was no significant difference in acute
      radiation-related toxicity between RT-groups but IFRT showed a significantly
      higher incidence of higher grade toxicities. Patients treated with INRT had a
      significantly better physical functioning and global quality of life compared to
      the IFRT group. CONCLUSIONS: Given the retrospective nature of this study, no
      solid conclusions can be drawn. However, in view of the equivalent efficacy and
      more favorable toxicity profile, the replacement of IFRT by INRT in combination
      with chemo-(immuno)-therapy looks very attractive for patients with early stage
      aggressive NHL.

PMID- 24021345
TI  - Multi-staged robotic stereotactic radiosurgery for large cerebral arteriovenous
      malformations.
AB  - PURPOSE: To investigate a multi-staged robotic stereotactic radiosurgery (SRS)
      delivery technique for the treatment of large cerebral arteriovenous
      malformations (AVMs). The treatment planning process and strategies to optimize
      both individual and composite dosimetry are discussed. METHODS: Eleven patients
      with large (30.7 +/- 19.2 cm(3)) AVMs were selected for this study. A fiducial
      system was designed for fusion of targets between planar angiograms and
      simulation CT scans. AVMs were contoured based on single contrast CT, MRI and
      orthogonal angiogram images. AVMs were divided into 3-8 sub-target volumes (3-7
      cm(3)) for sequential treatment at 1-4 week intervals to a prescription dose of
      16-20 Gy. Forward and inversely developed treatment plans were optimized for 95%
      coverage of the total AVM volume by dose summation from each sub-volume, while
      minimizing dose to surrounding tissues. Dose-volume analysis was used to evaluate
      the PTV coverage, dose conformality (CI), and R50 and V12 Gy parameters. RESULTS:
      The treatment workflow was commissioned and able to localize within 1mm. Inverse
      optimization outperformed forward planning for most patients for each index
      considered. Dose conformality was shown comparable to staged Gamma Knife
      treatments. CONCLUSION: The CyberKnife system is shown to be a practical delivery
      platform for multi-staged treatments of large AVMs using forward or inverse
      planning techniques.

PMID- 24021347
TI  - Is it possible to improve radiotherapy team members' communication skills? A
      randomized study assessing the efficacy of a 38-h communication skills training
      program.
AB  - BACKGROUND AND PURPOSE: Optimizing communication between radiotherapy team
      members and patients and between colleagues requires training. This study applies
      a randomized controlled design to assess the efficacy of a 38-h communication
      skills training program. MATERIAL AND METHODS: Four radiotherapy teams were
      randomly assigned either to a training program or to a waiting list. Team
      members' communication skills and their self-efficacy to communicate in the
      context of an encounter with a simulated patient were the primary endpoints.
      These encounters were scheduled at the baseline and after training for the
      training group, and at the baseline and four months later for the waiting list
      group. Encounters were audiotaped and transcribed. Transcripts were analyzed with
      content analysis software (LaComm) and by an independent rater. RESULTS: Eighty
      team members were included in the study. Compared to untrained team members,
      trained team members used more turns of speech with content oriented toward
      available resources in the team (relative rate [RR]=1.38; p=0.023), more
      assessment utterances (RR=1.69; p<0.001), more empathy (RR=4.05; p=0.037), more
      negotiation (RR=2.34; p=0.021) and more emotional words (RR=1.32; p=0.030), and
      their self-efficacy to communicate increased (p=0.024 and p=0.008, respectively).
      CONCLUSIONS: The training program was effective in improving team members'
      communication skills and their self-efficacy to communicate in the context of an
      encounter with a simulated patient. Future study should assess the effect of this
      training program on communication with actual patients and their satisfaction.
      Moreover a cost-benefit analysis is needed, before implementing such an intensive
      training program on a broader scale.

PMID- 24021346
TI  - Differential effect of soy isoflavones in enhancing high intensity radiotherapy
      and protecting lung tissue in a pre-clinical model of lung carcinoma.
AB  - BACKGROUND: Radiotherapy of locally-advanced non-small cell lung cancer is
      limited by radiation-induced pneumonitis and fibrosis. We have further
      investigated the role of soy isoflavones to improve the effect of a high
      intensity radiation and reduce lung damage in a pre-clinical lung tumor model.
      METHODS: Human A549 NSCLC cells were injected i.v. in nude mice to generate a
      large tumor burden in the lungs. Mice were treated with lung irradiation at 10 Gy
      and with oral soy. The therapy effect on the tumor cells and surrounding lung
      tissue was analyzed on lung sections stained with H&E, Ki-67 and Masson's
      Trichrome. Pneumonitis and vascular damage were evaluated by measurements of
      alveolar septa and immunofluorescent staining of vessel walls. RESULTS: Combined
      soy and radiation caused a significantly stronger inhibition of tumor progression
      compared to each modality alone in contrast to large invasive tumor nodules seen
      in control mice. At the same time, soy reduced radiation injury in lung tissue by
      decreasing pneumonitis, fibrosis and protecting alveolar septa, bronchioles and
      vessels. CONCLUSIONS: These studies demonstrate a differential effect of soy
      isoflavones on augmenting tumor destruction induced by radiation while
      radioprotecting the normal lung tissue and support using soy to alleviate
      radiotoxicity in lung cancer.

PMID- 24021348
TI  - Adaptive radiotherapy with an average anatomy model: evaluation and
      quantification of residual deformations in head and neck cancer patients.
AB  - BACKGROUND AND PURPOSE: To develop and validate an adaptive intervention strategy
      for radiotherapy of head-and-neck cancer that accounts for systematic
      deformations by modifying the planning-CT (pCT) to the average misalignments in
      daily cone beam CT (CBCT) measured with deformable registration (DR). METHODS AND
      MATERIALS: Daily CBCT scans (808 scans) for 25 patients were retrospectively
      registered to the pCT with B-spline DR. The average deformation vector field
      (<DVF>) was used to deform the pCT for adaptive intervention. Two strategies were
      simulated: single intervention after 10 fractions and weekly intervention with an
      <DVF> from the previous week. The model was geometrically validated with the
      residual misalignment of anatomical landmarks both on bony-anatomy (BA;
      automatically generated) and soft-tissue (ST; manually identified). RESULTS:
      Systematic deformations were 2.5/3.4mm vector length (BA/ST). Single intervention
      reduced deformations to 1.5/2.7 mm (BA/ST). Weekly intervention resulted in
      1.0/2.2mm (BA/ST) and accounted better for progressive changes. 15 patients had
      average systematic deformations >2mm (BA): reductions were 1.1/1.9 mm
      (single/weekly BA). ST improvements were underestimated due to observer and
      registration variability. CONCLUSIONS: Adaptive intervention with a pCT modified
      to the average anatomy during treatment successfully reduces systematic
      deformations. The improved accuracy could possibly be exploited in margin
      reduction and/or dose escalation.

PMID- 24021349
TI  - Phase II study of temozolomide in combination with topotecan (TOTEM) in relapsed
      or refractory neuroblastoma: a European Innovative Therapies for Children with
      Cancer-SIOP-European Neuroblastoma study.
AB  - PURPOSE: To assess objective response rate (ORR) after two cycles of temozolomide
      in combination with topotecan (TOTEM) in children with refractory or relapsed
      neuroblastoma. PATIENTS AND METHODS: This multicenter, non-randomised, phase II
      study included children with neuroblastoma according to a two-stage Simon design.
      Eligibility criteria included relapsed or refractory, measurable or
      metaiodobenzylguanidine (mIBG) evaluable disease, no more than two lines of prior
      treatment. Temozolomide was administered orally at 150mg/m(2) followed by
      topotecan at 0.75mg/m(2) intravenously for five consecutive days every 28days.
      Tumour response was assessed every two cycles according to International
      Neuroblastoma Response Criteria (INRC), and reviewed independently. RESULTS:
      Thirty-eight patients were enroled and treated in 15 European centres with a
      median age of 5.4years. Partial tumour response after two cycles was observed in
      7 out of 38 evaluable patients [ORR 18%, 95% confidence interval (CI) 8-34%]. The
      best ORR whatever the time of evaluation was 24% (95% CI, 11-40%) with a median
      response duration of 8.5months. Tumour control rate (complete response
      (CR)+partial response (PR)+mixed response (MR)+stable disease (SD)) was 68% (95%
      CI, 63-90%). The 12-months Progression-Free and Overall Survival were 42% and 58%
      respectively. Among 213 treatment cycles (median 4, range 1-12 per patient) the
      most common treatment-related toxicities were haematologic. Grade 3/4 neutropenia
      occurred in 62% of courses in 89% of patients, grade 3/4 thrombocytopenia in 47%
      of courses in 71% of patients; three patients (8%) had febrile neutropenia.
      CONCLUSION: Temozolomide-Topotecan combination results in very encouraging ORR
      and tumour control in children with heavily pretreated recurrent and refractory
      neuroblastoma with favourable toxicity profile.

PMID- 24021350
TI  - Dipyridamole analogs as pharmacological inhibitors of equilibrative nucleoside
      transporters. Identification of novel potent and selective inhibitors of the
      adenosine transporter function of human equilibrative nucleoside transporter 4
      (hENT4).
AB  - To identify needed human equilibrative nucleoside transporter 4 (hENT4)
      inhibitors, we cloned and stably expressed the recombinant protein in PK15NTD
      (nucleoside transporter deficient) cells, and, investigated its interaction with
      a series of dipyridamole analogs synthesized in our laboratory. Compounds were
      tested in this newly established hENT4 expressing system as well in previous
      stably expressed hENT1 and hENT2 expressing systems. Of the dipyridamole analogs
      evaluated, about one fourth of the compounds inhibited hENT4 with higher
      potencies than dipyridamole. The most potent of them, Compound 30 displayed an
      IC50 of 74.4 nM, making it about 38 times more potent than dipyridamole (IC50=2.8
      MUM), and selectivities of about 80-fold and 20-fold relative to ENT1 and ENT2,
      respectively. Structure-activity relationship showed nitrogen-containing
      monocyclic rings and noncyclic substituents at the 4- and 8-positions of the
      pyrimido[5,4-d]pyrimidine were important for the inhibitory activity against
      hENT4. The most potent and selective hENT4 inhibitors tended to have a 2,6-di(N
      monohydroxyethyl) substitution on the pyrimidopyrimidine ring system. The
      inhibitors of hENT4 identified in this study are the most selective and potent
      inhibitors of hENT4 adenosine transporter function to date, and should serve as
      useful pharmacological/biochemical tools and/or potential leads for ENT4-based
      therapeutics. Also, the new hENT4-expressing PK15 cell line established will
      serve as a useful screening tool for the discovery and design of hENT4 ligands.

PMID- 24021351
TI  - Rutin inhibits B[a]PDE-induced cyclooxygenase-2 expression by targeting EGFR
      kinase activity.
AB  - Rutin is a well-known flavonoid that exists in various natural sources.
      Accumulative studies have represented the biological effects of rutin, such as
      anti-oxidative and anti-inflammatory effects. However, the underlying mechanisms
      of rutin and its direct targets are not understood. We investigated whether rutin
      reduced B[a]PDE-induced-COX-2 expression. The transactivation of AP-1 and NF
      kappaB were inhibited by rutin. Rutin also attenuated B[a]PDE-induced Raf/MEK/ERK
      and Akt activation, but had no effect on the phosphorylation of EGFR. An in vitro
      kinase assay revealed rutin suppressed EGFR kinase activity. We also confirmed
      direct binding between rutin and EGFR, and found that the binding was regressed
      by ATP. The EGFR inhibitor also inhibited the B[a]PDE-induced MEK/ERK and Akt
      signaling pathways and subsequently, suppressed COX-2 expression and promoter
      activity, in addition to suppressing the transactivation of AP-1 and NF-kappaB.
      In EGFR(-/-)mouse embryonic fibroblast cells, B[a]PDE-induced COX-2 expression
      was also diminished. Collectively, rutin inhibits B[a]PDE-induced COX-2
      expression by suppressing the Raf/MEK/ERK and Akt signaling pathways. EGFR
      appeared to be the direct target of rutin. 

PMID- 24021353
TI  - On the use of immortalized ocular cell lines in vision research: the unfortunate
      story of RGC-5.

PMID- 24021352
TI  - 3-O-methylthespesilactam, a new small-molecule anticancer pan-JAK inhibitor
      against A2058 human melanoma cells.
AB  - Natural product-inspired discovery of new drug leads plays a key role in drug
      development. Recently, small-molecule JAK inhibitors have been pursued for the
      development of anticancer therapeutics. However, most of these inhibitors
      reported up to now are multi-nitrogen polycyclic aromatic heterocycles.
      Undoubtedly, the discovery of new types of promising JAK-inhibitory leads is
      pivotal for JAK inhibitor-based anticancer drug development. Herein we report an
      unprecedented sesquiterpenoid-alkaloid named thespesilactam, containing a
      benzo[cd]indole scaffold, from the heartwood of the Portia tree, Thespesia
      populnea. Its 3-O-Me product, i.e. 8-hydroxy-5-isopropyl-3-methoxy-7
      methylbenzo[cd]indol-2(1H)-one, named 3-O-methylthespesilactam, of which the
      structure was identified by NMR investigations and single-crystal X-ray
      diffraction analysis, was discovered as a new type of small-molecule anticancer
      pan-JAK inhibitor against A2058 human melanoma cells, and selective and potent
      inhibitor of JAK1 and TYK2. 

PMID- 24021354
TI  - Factors influencing perceived sustainability of Dutch community health programs.
AB  - We assessed the perceived sustainability of community health programs organized
      by local intersectoral coalitions, as well as the factors that collaborating
      partners think might influence sustainability. Semi-structured interviews were
      conducted among 31 collaborating partners of 5 community health programs in
      deprived neighborhoods in the southern part of the Netherlands. The interview
      guide was based on a conceptual framework that includes factors related to the
      context, the leading organization, leadership, the coalition, collaborating
      partners, interventions and outcomes. Interviews were recorded, transcribed and
      content analyzed using NVivo 8.0. Participants in each of the programs varied in
      their perceptions of the sustainability of the program, but those people
      collaborating in pre-existing neighborhood structures expressed relatively high
      faith in their continuation. The participating citizens in particular believed
      that these structures would continue to address the health of the community in
      the future. We found factors from all categories of the conceptual framework that
      were perceived to influence sustainability. The program leaders appeared to be
      crucial to the programs, as they were frequently mentioned in close interaction
      with other factors. Program leaders should use a motivating and supportive
      leadership style and should act as 'program champions'. 

PMID- 24021355
TI  - The human frontal lobes: not relatively large but still disproportionately
      important? A commentary on Barton and Venditti.

PMID- 24021356
TI  - The nature of peptide interactions with acid end-group PLGAs and facile aqueous
      based microencapsulation of therapeutic peptides.
AB  - An important poorly understood phenomenon in controlled-release depots involves
      the strong interaction between common cationic peptides and low Mw free acid end
      group poly(lactic-co-glycolic acids) (PLGAs) used to achieve continuous peptide
      release kinetics. The kinetics of peptide sorption to PLGA was examined by
      incubating peptide solutions of 0.2-4mM octreotide or leuprolide acetate salts in
      a 0.1M HEPES buffer, pH7.4, with polymer particles or films at 4-37 degrees C for
      24h. The extent of absorption/loading of peptides in PLGA particles/films was
      assayed by two-phase extraction and amino acid analysis. Confocal Raman
      microspectroscopy, stimulated Raman scattering (SRS) and laser scanning confocal
      imaging, and microtome sectioning techniques were used to examine peptide
      penetration into the polymer phase. The release of sorbed peptide from leuprolide
      PLGA particles was evaluated both in vitro (PBST+0.02% sodium azide, 37 degrees
      C) and in vivo (male Sprague-Dawley rats). We found that when the PLGA-COOH
      chains are sufficiently mobilized, therapeutic peptides not only bind at the
      surface, a common belief to date, but also can be internalized and distributed
      throughout the polymer phase at physiological temperature forming a salt with low
      molecular weight PLGA-COOH. Importantly, absorption of leuprolide into low MW
      PLGA-COOH particles yielded ~17 wt.% leuprolide loading in the polymer (i.e.,
      ~70% of PLGA-COOH acids occupied), and the absorbed peptide was released from the
      polymer for >2 weeks in a controlled fashion in vitro and as indicated by
      sustained testosterone suppression in male Sprague-Dawley rats. This new
      approach, which bypasses the traditional encapsulation method and associated
      production cost, opens up the potential for facile production of low-cost
      controlled-release injectable depots for leuprolide and related peptides.

PMID- 24021357
TI  - In vivo imaging of myocardial cell death using a peptide probe and assessment of
      long-term heart function.
AB  - During acute myocardial infarction (AMI), both apoptosis and necrosis of
      myocardial cells could occur and lead to left ventricular (LV) functional
      decline. Here we determined whether in vivo imaging signals of myocardial cell
      death by ApoPep-1 (CQRPPR), a peptide probe that binds to apoptotic and necrotic
      cells through histone H1, at an early stage after AMI showed correlation with the
      long-term heart function. AMI was induced using a rat model of ischemia and
      reperfusion (I/R) injury. Fluorescence-labeled ApoPep-1 was administered by
      intravenous injection into rats 2h after reperfusion. Ex vivo imaging of hearts
      isolated 2h after peptide injection showed higher levels of near-infrared
      fluorescence (NIRF) signals at hearts of I/R rats than those of sham-operated
      rats. The fluorescent peptide was rapidly cleared from the blood and did not bind
      to red and white blood cells. Localization of fluorescent ApoPep-1 at the area of
      cell death was demonstrated by co-staining of myocardial tissue with TUNEL. The
      intensity of in vivo NIRF imaging signals by homing of ApoPep-1 to injured
      myocardium of I/R rats obtained 2h after peptide injection (equivalent to 4h
      after injury) showed strong and moderate correlation with the change in the LV
      ejection fractions (r(2)=0.82) and the size of the fibrotic area (r(2)=0.64),
      respectively, observed at four weeks after injury. These results suggest that
      ApoPep-1-mediated in vivo imaging signals of myocardial cell death, including
      both apoptosis and necrosis, at an early stage of AMI could be a potential
      biomarker for assessment of long-term outcome of heart function. 

PMID- 24021358
TI  - Tumor perfusion imaging predicts the intra-tumoral accumulation of liposomes.
AB  - Liposomes have proven to be a viable drug delivery strategy resulting in
      significant increases in tumor accumulation of drugs via exploitation of the
      enhanced permeability and retention (EPR) effect. However, significant
      variability has been observed in their bulk tumor accumulation and intra-tumoral
      distribution. The heterogeneous accumulation of liposomes in solid tumors is
      largely believed to result from the chaotic morphology and physiology of tumor
      blood vessels. Thus, tumor perfusion imaging may provide a novel method to
      predict the accumulation and resulting therapeutic effect of liposome
      formulations. In this study, dynamic contrast enhanced computed tomography (DCE
      CT) was employed to quantitatively estimate the intra-tumoral distribution of
      perfusion and anatomical CT was used to map the spatio-temporal accumulation of a
      CT-liposome contrast agent. A statistically significant positive correlation was
      found between quantitative and semi-quantitative measures of tumor perfusion
      (i.e. K(trans), vp, and AUC(iox)) and liposome accumulation (AUC(lipo) and
      C(peak)) in two mouse xenograft models of human cervical cancer. Specifically, it
      was found that regions with higher K(trans),vp, and AUC(iox) had greater liposome
      accumulation. These findings demonstrate that DCE-CT measurements of tumor
      perfusion may be an important technique for selecting patients that are likely to
      respond to liposome and potentially other nanoparticle-based therapies.

PMID- 24021359
TI  - An oral malaria therapy: curcumin-loaded lipid-based drug delivery systems
      combined with beta-arteether.
AB  - Curcumin (CC), a potential antimalarial drug, has poor water solubility,
      stability and oral bioavailability. To circumvent these pitfalls, lipid-based
      drug delivery systems (LBDDSs) with a high CC loading (30 mg/g) were formulated.
      In a biorelevant gastric medium, CC-LBDDSs formed particle sizes in the range of
      30-40 nm. During in vitro lipolysis, 90-95% of the CC remained solubilized,
      whereas 5-10% of the CC precipitated as an amorphous solid, with a high rate of
      re-dissolution in a biorelevant intestinal medium. The transport of the CC-LBDDS
      across Caco-2 monolayers was enhanced compared with the transport of free drug
      because of the increased CC solubility. In Plasmodium berghei-infected mice,
      modest antimalarial efficacy was observed following oral treatment with CC
      LBDDSs. However, the combination therapy of CC-LBDDS with a subtherapeutic dose
      of beta-arteether-LBDDS provided an increase in protection and survival rate that
      was associated with a significant delay in recrudescence. These findings suggest
      that the combination of oral CC and beta-arteether lipid-based formulations may
      constitute a promising approach for the treatment of malaria.

PMID- 24021360
TI  - Two-year outcome of internet-based relapse prevention for partially remitted
      depression.
AB  - The objective of the study was to investigate the long-term effects of internet
      based relapse prevention for sufferers of partially remitted depression. Eighty
      four individuals with partially remitted unipolar depression were randomized to
      either internet-based CBT (iCBT) or to a control group. After the ten week
      intervention period the participants were followed for 24 months and diagnostic
      interviews conducted to detect relapse. The intervention and monthly self-ratings
      of depressive symptoms were administered via an internet-based platform that
      ensured secure communication with all participants. Significantly fewer
      participants in the iCBT group had experienced a relapse compared with those in
      the control group two years after the internet-based intervention. The relapse
      rate in the iCBT group was 13.7% (CI 95%=2.5-24.9) and in the control group it
      was 60.9% (CI 95%=44.8-77). Furthermore, a significantly larger proportion of the
      iCBT group experienced remission two years after the intervention compared with
      the control group. Internet-based CBT seems promising for preventing relapse in
      sufferers of partially remitted depression.

PMID- 24021361
TI  - Hidradenitis suppurativa: A practical review of possible medical treatments based
      on over 350 hidradenitis patients.
AB  - Hidradenitis suppurativa (HS), a pathological follicular disease, impacts
      patients' lives profoundly. HS most commonly involves cutaneous intertriginous
      areas, such as the axilla, inner thighs, groin and buttocks, and pendulous
      breasts, but can appear on any follicular skin. Protean, HS manifests with
      variations of abscesses, folliculitis, pyogenic granulomas, scars (oval
      honeycombed), comedones, tracts, fistulas, and keloids. The pathophysiology might
      involve both defects of the innate follicular immunity and overreaction to
      coagulase negative Staphylococcus. Treatment depends on the morphology, extent,
      severity, and duration. Topical clindamycin and dapsone are often adequate for
      treating mild HS. For Stage 1 and 2 HS, first line treatment combines rifampin
      with either oral clindamycin or minocycline. Other HS treatments include:
      fluoroquinolones with metronidazole and rifampin, oral dapsone, zinc, acitretin,
      hormone blockers (oral contraceptive pills, spironolactone, finasteride, and
      dutasteride), and oral prednisone. For severe HS, cyclosporine, adalimumab, or
      infliximab (used at double psoriatic doses) and intravenous carbapenems or
      cephalosporins are often required. Isotretinoin, etanercept, isoniazid,
      lymecycline, sulfasalazine, methotrexate, metformin, colchicine, clarithromycin,
      IVIG, and thalidomide are less favored treatments. The role of botulinum toxin is
      uncertain. The most important life style modification is weight loss. De-roofing
      fluctuant nodules and injection of intralesional corticosteroids ameliorates the
      disease and perhaps, if done at regular intervals, improves HS more permanently.
      Surgical excision and CO2 laser ablation are more definitive treatments. The 1064
      nm laser for hair removal aids in the treatment of HS. This article centers on
      medical therapies and will only passingly mention surgical and laser treatments.
      This article summarizes my treatment experience with over 350 HS patients. 

PMID- 24021362
TI  - Epidermodysplasia verruciformis associated with HPV 10.
AB  - Epidermodysplasia verruciformis (EV) is a rare, inherited dermatologic condition
      demonstrating an increased susceptibility to specific HPV genotypes, resulting in
      both benign and malignant skin lesions. Epidermodysplasia verruciformis lesions
      are frequently described as pityriasis versicolor-like scaly macules, flat wart
      like papules, or verrucous and seborrhic keratosis-like papules and plaques.
      Acquired EV has been described in patients with HIV and in those who are on
      immunosuppressive therapy. We discuss a patient with congenital EV who presents
      with skin lesions associated with HPV 10, a less frequently cited causative
      subtype, and histological findings that are not classic for EV. 

PMID- 24021363
TI  - Perianal and periumbilical dermatitis: Report of a woman with group G
      streptococcal infection and review of perianal and periumbilical dermatoses.
AB  - PURPOSE: We describe a woman with perianal and periumbilical dermatitis secondary
      to group G Streptococcus, summarize the salient features of this condition, and
      review other cutaneous conditions that clinically mimic streptococcal dermatitis
      of the umbilicus. BACKGROUND: Periumbilical and perianal streptococcal dermatitis
      are conditions that commonly occur in children and usually result from beta
      hemolytic group A Streptococcus. Rarely, non-group A streptococcal and
      staphylococcal infections have been reported in adults. MATERIALS AND METHODS: A
      31-year-old woman developed perianal and periumbilical group G streptococcal
      dermatitis. Symptoms were present for six months and were refractory to
      clotrimazole 1 percent and betamethasone dipropionate 0.05 percent cream.
      RESULTS: The etiology of perianal and periumbilical dermatitis is unclear, but is
      perhaps explained by virulence of previously asymptomatic colonized bacteria.
      Perianal streptococcal dermatitis is more common in children. A number of adult
      infections have been reported, most of which were secondary to group A beta
      hemolytic Streptococcus. Men are more often affected than women. Group G
      Streptococcus is rarely the infective etiology of perianal streptococcal
      dermatitis. This condition presents as a superficial well demarcated erythematous
      patch on clinical examination. Diagnosis is ascertained by diagnostic swabs and
      serological tests: antistreptolysin O (ASO) or anti-DNase titer. Treatments
      include oral amoxicillin, penicillin, erythromycin, and mupirocin ointment.
      CONCLUSIONS: Our patient expands on the clinical presentation typical of
      streptococcal dermatitis. We describe a rare occurrence of an adult woman
      infected with non-group A Streptococcus. Several conditions can mimic the
      presentation of perianal streptococcal dermatitis. Although rare, group G
      Streptococcus should be considered in the setting of virulent infections usually
      attributed to group A species. Streptococcal dermatitis can be added to the list
      of conditions affecting the umbilicus.

PMID- 24021364
TI  - A case of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) related to
      rufinamide.
AB  - Drug Rash (or Reaction) with Eosinophilia and Systemic Symptoms (DRESS) is a
      potentially life-threatening hypersensitivity reaction to drugs characterized by
      rash, fever, lymphadenopathy, hematologic abnormalities, and involvement of
      internal organs. Initially coined in 1996, the term is used to refer to an
      idiosyncratic reaction to several drugs, the most common of which are
      carbamazepine, allopurinol, sulfasalazine, and phenobarbital. We report the first
      case of DRESS related to rufinamide in a ten year old boy with a history of a
      complex seizure disorder. 

PMID- 24021365
TI  - Shiitake mushroom-induced flagellate erythema: A striking case and review of the
      literature.
AB  - Ingestion of raw or undercooked shiitake mushrooms is associated with a
      distinctive flagellate erythema. We describe a 61-year-old Caucasian man who
      presented with a pruritic, erythematous eruption of multiple linear streaks on
      the trunk and extremities starting 1 day after eating raw shiitake mushrooms. His
      symptoms and skin lesions resolved with minimal hyperpigmentation within
      approximately 1 week after treating with topical steroids and oral
      antihistamines. Skin biopsy showed non-specific findings, including a sparse
      perivascular and interstitial dermatitis as well as focal vacuolar interface
      changes. Our case illustrates that this condition is a visibly striking
      dermatitis with a self-limited course. The pathomechanism of the skin eruption
      remains unclear. 

PMID- 24021366
TI  - [POPP syndrome: Psoriatic onychopachydermoperiostitis].
AB  - Psoriatic onychopachydermoperiostitis (POPP) syndrome characterizes a clinical
      variant of psoriatic arthritis originally described by Fournie et al in 1989.
      Both great toes are generally affected presenting with nail changes, painful
      swelling of the soft tissue close to the distal phalanx as well as specific
      radiologic changes such as periosteal reaction and bone erosions of the distal
      phalanges. Joint involvement is characteristically absent and classic psoriatic
      lesions may be associated. Painful symptoms may lead to severe functional and
      quality of life impairment. Traditional systemic treatment is generally
      frustrating. Here we report a female patient presenting POPP syndrome refractory
      to traditional systemic treatments and adalimumab, further presenting a favorable
      response to treatment with etanercept. 

PMID- 24021367
TI  - A case of Hansen Disease presenting as tinea versicolor.
AB  - Hansen Disease (leprosy) is an infectious disease that targets macrophages and
      Schwann cells, caused by the acid fast intracellular organism, Mycobacterium
      leprae. Clinically, it presents with a spectrum of findings that may include
      hypopigmented macules, erythematous plaques and nodules, and thickened or tender
      peripheral nerves. The most feared complication is mutilating damage to facial
      structures or digits resulting from loss of sensation in affected skin. In non
      endemic areas, the diagnosis of leprosy is frequently delayed because it may
      mimic other more common skin conditions. We present a case of
      borderline/lepromatous leprosy in an otherwise healthy young Brazilian man that
      was initially diagnosed as tinea versicolor, but did not respond to appropriate
      treatment. This case highlights the importance of having a high index of
      suspicion for leprosy in patients from endemic areas who present with lesions
      that could be consistent with this disease. 

PMID- 24021368
TI  - Congenital subungual melanocytic nevus with a pseudo-Hutchinson sign.
AB  - We describe a 29-year-old woman with congenital melanonychia striata and compound
      nevus of the right first digit. There was extension of the hyperpigmentation onto
      the proximal nail fold, even beyond the borders established by the band of
      melanonychia striata. A dermal plaque with irregular borders and variegated
      pigmentation was also present over the distal digit extending from the pigmented
      region of the hyponychium. A limited number of biopsy proven congenital subungual
      melanocytic nevi have been reported in the literature. Interestingly, we found
      that the majority of these cases present with longitudinal melanonychia in
      association with periungual hyperpigmentation, constituting a pseudo-Hutchinson
      sign. Currently studies evaluating the diagnostic test characteristics of
      Hutchinson sign are lacking. While Hutchinson sign is traditionally considered a
      worrisome feature it is certainly not pathognomonic and a malignant cause should
      not be assumed without thorough assessment. 

PMID- 24021369
TI  - Preradial myxedema in a euthyroid male: A distinct rarity.
AB  - Localized or pretibial myxedema is one of the signs of Graves disease (along with
      goiter, exophthalmus, thyroid acropathy, and high circulating levels of long
      acting thyroid-stimulating hormone) and usually tends to occur at a later stage
      of the disease or even after the patient becomes euthyroid post treatment. Very
      rarely has it been reported in euthyroid patients. We report a euthyroid man
      presenting with localized myxedema on the extensor surface of his forearm with
      clinical and histopathological features consistent with pretibial myxedema. He
      responded partially to topical clobetasol propionate cream and tacrolimus
      ointment 0.1 percent for about 7 months. To the best of our knowledge, this is
      the first case of preradial myxedema in a euthyroid patient in the English
      international dermatological literature. 

PMID- 24021370
TI  - A case of nodular cutaneous amyloidosis and review of the literature.
AB  - Nodular cutaneous amyloidosis (NCA) is the rarest form of primary cutaneous
      amyloidosis. The amyloid fibrils of NCA are not unique to NCA but are also the
      prevailing amyloid component in primary systemic amyloidosis (PSA) and myeloma
      associated systemic amyloidosis. Age of presentation in NCA has ranged from 20 to
      87 years without a clear gender predilection. Progression from NCA to primary
      systemic amyloidosis has been reported, with an estimated lifetime risk of
      approximately 7 percent, prompting the need for appropriate follow up to evaluate
      for the presence of systemic amyloidosis. We report a case of nodular cutaneous
      amyloidosis in an otherwise healthy 62-year-old woman and we review the
      literature. 

PMID- 24021371
TI  - The longest faun tail forming dreadlocks with underlying spina bifida occulta.
AB  - Spina bifida is a developmental anomaly characterized by defective closure of the
      bony encasement of the spinal cord through which the spinal cord and meninges may
      or may not protrude. We report a rare case of a very long faun tail, which was in
      the form of a 20 inch long tail originating from the lumbosacral area in a
      rhomboidal pattern, measuring 10 x 8 inches. The case is being reported for its
      rare presentation of a 20 inch long faun tail with underlying spina bifida
      occulta. 

PMID- 24021372
TI  - [Bacterial lip abscess in an immunocompetent patient].
AB  - Lip abscesses are a potentially serious condition rarely reported in the medical
      literature. This disease requires prompt diagnosis and treatment with
      hospitalization, intravenous antibiotics, and urgent surgical drainage. Clinical
      knowledge of this condition is essential to guide the differential diagnosis and
      correctly adapt the etiological treatment. The presence of necrotic and cavitated
      lesions requires ruling out immunosupression or methicillin-resistant agent. We
      report a necrotic and cavitated bacterial lip abscess caused by methicillin
      sensitive Staphylococcus aureus in an immunocompetent male. 

PMID- 24021373
TI  - Cancellations and patient access to physicians: ZocDoc and the evolution of e
      medicine.
AB  - BACKGROUND: Appointment attendance has always been a concern for physicians and
      the landscape is changing now that patients can book appointments online in many
      practices. OBJECTIVE: This manuscript examined attendance rates of appointments
      made on the internet for rural and urban dermatology clinics. METHODS: The study
      analyzed appointment records made over a 6-month period on ZocDoc.com for 3
      dermatology clinics located outside Houston, Texas. RESULTS: Non-attendance rates
      for online appointments were much lower (6.9%) than non-attendance rates at
      dermatology clinics through traditional means. The average age of patients who
      missed their appointments was lower than the average age of those who made their
      appointments. In addition, the average age of those who cancelled their
      appointments was higher than those who made their appointments. Also, urban non
      attendance rates were higher than rural rates. LIMITATIONS: This study has a
      small sample size because online appointment scheduling is not a common practice.
      CONCLUSION: The early returns of online appointment scheduling indicate that
      appointments made online are more likely to have lower non-attendance rates than
      appointments made through traditional means.

PMID- 24021374
TI  - In vivo antinuclear antibodies of the skin: A rare phenomenon on direct
      immunofluorescence.
AB  - Detection of immunoglobulins in epidermal cell nuclei or in vivo antinuclear
      antibodies on direct immunoflorescence microscopy of skin biopsies is an easily
      detectable immunopathologic feature. It is an unusual, but not totally rare,
      occurrence in systemic connective tissue disorders. This positive epidermal
      nuclear reaction is found to be commonly associated with immunoglobulin G. 

PMID- 24021375
TI  - Vemurafenib-associated neutrophilic panniculitis: An emergent adverse effect of
      variable severity.
AB  - Vemurafenib is a selective BRAF kinase inhibitor recently proven to improve rates
      of overall and progression-free survival in patients with BRAF-V600-mutant
      metastatic melanoma. The most common adverse effects of this targeted therapy are
      arthralgia, fatigue, and cutaneous lesions, including alopecia, photosensitivity,
      pruritus, hand-foot skin reactions, squamous cell carcinomas, keratoacanthomas,
      warty dyskeratomas and verrucous keratosis. Less frequently, cases of
      panniculitis of varying severity have been reported in patients receiving
      vemurafenib. In this report, we describe a patient who developed asymptomatic
      nodules on her legs, with complete, spontaneous resolution, while on vemurafenib
      therapy. A causal relationship was considered likely because of the timing of
      occurrence and the absence of other potential causes after extensive assessment.
      Vemurafenib therapy was continued at full dosage and no recurrences were
      observed. We believe that management of lobular panniculitis associated with
      selective BRAF inhibitors should vary according to the clinical presentation,
      degree of systemic involvement, and presence of joint inflammation. Physicians
      should be aware of this emergent side effect. Treatment discontinuation should be
      considered on a case-by-case basis because the condition may resolve
      spontaneously. 

PMID- 24021376
TI  - Blaschkoid lichen planus: Not a Koebner phenomenon.
AB  - Linear lichen planus (LP) is commonly seen as an effect of the koebner phenomenon
      and can occur in any site. However, LP in a whorl pattern along Blaschko lines is
      rarely mentioned in the literature. We highlight this rare form in a 32-year-old
      female with multiple hyperpigmented lesions with various patterns along the lines
      of Blaschko on the left side of the trunk. The clinical and histological findings
      were suggestive of LP. 

PMID- 24021377
TI  - A dramatic case of Behcet disease successfully treated with infliximab.
AB  - Behcet disease is a chronic relapsing systemic disease with possible life
      threatening presentations. Management of this disease can be challenging and
      reports of the off-label use of anti-TNFalpha agents for the treatment of severe
      manifestations are increasing, with good results. The authors report a case of
      Behcet disease with a sudden and severe multi-systemic onset successfully treated
      with infliximab. 

PMID- 24021378
TI  - Transversely sectioned biopsies in the diagnosis of end-stage traction alopecia.
AB  - The pathogenesis of scarring alopecia in African American women remains poorly
      understood. Furthermore, the overlapping clinical and histological features
      present diagnostic challenges. The diagnosis of end stage traction alopecia
      secondary to traumatic hair styling practices can sometimes present particular
      challenges. We present a young African American woman with a scarring alopecia.
      As we describe, a scalp biopsy processed by transverse sections enabled rapid
      diagnosis and presented advantages over a biopsy processed with vertical
      sections. 

PMID- 24021379
TI  - eSBMTools 1.0: enhanced native structure-based modeling tools.
AB  - MOTIVATION: Molecular dynamics simulations provide detailed insights into the
      structure and function of biomolecular systems. Thus, they complement
      experimental measurements by giving access to experimentally inaccessible
      regimes. Among the different molecular dynamics techniques, native structure
      based models (SBMs) are based on energy landscape theory and the principle of
      minimal frustration. Typically used in protein and RNA folding simulations, they
      coarse-grain the biomolecular system and/or simplify the Hamiltonian resulting in
      modest computational requirements while achieving high agreement with
      experimental data. eSBMTools streamlines running and evaluating SBM in a
      comprehensive package and offers high flexibility in adding experimental- or
      bioinformatics-derived restraints. RESULTS: We present a software package that
      allows setting up, modifying and evaluating SBM for both RNA and proteins. The
      implemented workflows include predicting protein complexes based on
      bioinformatics-derived inter-protein contact information, a standardized setup of
      protein folding simulations based on the common PDB format, calculating reaction
      coordinates and evaluating the simulation by free-energy calculations with
      weighted histogram analysis method or by phi-values. The modules interface with
      the molecular dynamics simulation program GROMACS. The package is open source and
      written in architecture-independent Python2. AVAILABILITY:
      http://sourceforge.net/projects/esbmtools/. CONTACT: alexander.schug@kit.edu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 24021380
TI  - Precise inference of copy number alterations in tumor samples from SNP arrays.
AB  - MOTIVATION: The accurate detection of copy number alterations (CNAs) in human
      genomes is important for understanding susceptibility to cancer and mechanisms of
      tumor progression. CNA detection in tumors from single nucleotide polymorphism
      (SNP) genotyping arrays is a challenging problem due to phenomena such as
      aneuploidy, stromal contamination, genomic waves and intra-tumor heterogeneity,
      issues that leading methods do not optimally address. RESULTS: Here we introduce
      methods and software (PennCNV-tumor) for fast and accurate CNA detection using
      signal intensity data from SNP genotyping arrays. We estimate stromal
      contamination by applying a maximum likelihood approach over multiple discrete
      genomic intervals. By conditioning on signal intensity across the genome, our
      method accounts for both aneuploidy and genomic waves. Finally, our method uses a
      hidden Markov model to integrate multiple sources of information, including total
      and allele-specific signal intensity at each SNP, as well as physical maps to
      make posterior inferences of CNAs. Using real data from cancer cell-lines and
      patient tumors, we demonstrate substantial improvements in accuracy and
      computational efficiency compared with existing methods.

PMID- 24021381
TI  - HMCan: a method for detecting chromatin modifications in cancer samples using
      ChIP-seq data.
AB  - MOTIVATION: Cancer cells are often characterized by epigenetic changes, which
      include aberrant histone modifications. In particular, local or regional
      epigenetic silencing is a common mechanism in cancer for silencing expression of
      tumor suppressor genes. Though several tools have been created to enable
      detection of histone marks in ChIP-seq data from normal samples, it is unclear
      whether these tools can be efficiently applied to ChIP-seq data generated from
      cancer samples. Indeed, cancer genomes are often characterized by frequent copy
      number alterations: gains and losses of large regions of chromosomal material.
      Copy number alterations may create a substantial statistical bias in the
      evaluation of histone mark signal enrichment and result in underdetection of the
      signal in the regions of loss and overdetection of the signal in the regions of
      gain. RESULTS: We present HMCan (Histone modifications in cancer), a tool
      specially designed to analyze histone modification ChIP-seq data produced from
      cancer genomes. HMCan corrects for the GC-content and copy number bias and then
      applies Hidden Markov Models to detect the signal from the corrected data. On
      simulated data, HMCan outperformed several commonly used tools developed to
      analyze histone modification data produced from genomes without copy number
      alterations. HMCan also showed superior results on a ChIP-seq dataset generated
      for the repressive histone mark H3K27me3 in a bladder cancer cell line. HMCan
      predictions matched well with experimental data (qPCR validated regions) and
      included, for example, the previously detected H3K27me3 mark in the promoter of
      the DLEC1 gene, missed by other tools we tested.

PMID- 24021382
TI  - A simulator for spatially extended kappa models.
AB  - Spatial Kappa is a simulator of models written in a variant of the rule-based
      stochastic modelling language Kappa, with spatial extensions.

PMID- 24021383
TI  - Accounting for epistatic interactions improves the functional analysis of protein
      structures.
AB  - MOTIVATION: The constraints under which sequence, structure and function coevolve
      are not fully understood. Bringing this mutual relationship to light can reveal
      the molecular basis of binding, catalysis and allostery, thereby identifying
      function and rationally guiding protein redesign. Underlying these relationships
      are the epistatic interactions that occur when the consequences of a mutation to
      a protein are determined by the genetic background in which it occurs. Based on
      prior data, we hypothesize that epistatic forces operate most strongly between
      residues nearby in the structure, resulting in smooth evolutionary importance
      across the structure. METHODS AND RESULTS: We find that when residue scores of
      evolutionary importance are distributed smoothly between nearby residues,
      functional site prediction accuracy improves. Accordingly, we designed a novel
      measure of evolutionary importance that focuses on the interaction between pairs
      of structurally neighboring residues. This measure that we term pair-interaction
      Evolutionary Trace yields greater functional site overlap and better structure
      based proteome-wide functional predictions. CONCLUSIONS: Our data show that the
      structural smoothness of evolutionary importance is a fundamental feature of the
      coevolution of sequence, structure and function. Mutations operate on individual
      residues, but selective pressure depends in part on the extent to which a
      mutation perturbs interactions with neighboring residues. In practice, this
      principle led us to redefine the importance of a residue in terms of the
      importance of its epistatic interactions with neighbors, yielding better
      annotation of functional residues, motivating experimental validation of a novel
      functional site in LexA and refining protein function prediction. CONTACT:
      lichtarge@bcm.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 24021384
TI  - BioPig: a Hadoop-based analytic toolkit for large-scale sequence data.
AB  - MOTIVATION: The recent revolution in sequencing technologies has led to an
      exponential growth of sequence data. As a result, most of the current
      bioinformatics tools become obsolete as they fail to scale with data. To tackle
      this 'data deluge', here we introduce the BioPig sequence analysis toolkit as one
      of the solutions that scale to data and computation. RESULTS: We built BioPig on
      the Apache's Hadoop MapReduce system and the Pig data flow language. Compared
      with traditional serial and MPI-based algorithms, BioPig has three major
      advantages: first, BioPig's programmability greatly reduces development time for
      parallel bioinformatics applications; second, testing BioPig with up to 500 Gb
      sequences demonstrates that it scales automatically with size of data; and
      finally, BioPig can be ported without modification on many Hadoop
      infrastructures, as tested with Magellan system at National Energy Research
      Scientific Computing Center and the Amazon Elastic Compute Cloud. In summary,
      BioPig represents a novel program framework with the potential to greatly
      accelerate data-intensive bioinformatics analysis.

PMID- 24021385
TI  - Toward a statistically explicit understanding of de novo sequence assembly.
AB  - MOTIVATION: Draft de novo genome assemblies are now available for many organisms.
      These assemblies are point estimates of the true genome sequences. Each is a
      specific hypothesis, drawn from among many alternative hypotheses, of the
      sequence of a genome. Assembly uncertainty, the inability to distinguish between
      multiple alternative assembly hypotheses, can be due to real variation between
      copies of the genome in the sample, errors and ambiguities in the sequenced data
      and assumptions and heuristics of the assemblers. Most assemblers select a single
      assembly according to ad hoc criteria, and do not yet report and quantify the
      uncertainty of their outputs. Those assemblers that do report uncertainty take
      different approaches to describing multiple assembly hypotheses and the support
      for each. RESULTS: Here we review and examine the problem of representing and
      measuring uncertainty in assemblies. A promising recent development is the
      implementation of assemblers that are built according to explicit statistical
      models. Some new assembly methods, for example, estimate and maximize assembly
      likelihood. These advances, combined with technical advances in the
      representation of alternative assembly hypotheses, will lead to a more complete
      and biologically relevant understanding of assembly uncertainty. This will in
      turn facilitate the interpretation of downstream analyses and tests of specific
      biological hypotheses.

PMID- 24021386
TI  - Explicet: graphical user interface software for metadata-driven management,
      analysis and visualization of microbiome data.
AB  - Studies of the human microbiome, and microbial community ecology in general, have
      blossomed of late and are now a burgeoning source of exciting research findings.
      Along with the advent of next-generation sequencing platforms, which have
      dramatically increased the scope of microbiome-related projects, several high
      performance sequence analysis pipelines (e.g. QIIME, MOTHUR, VAMPS) are now
      available to investigators for microbiome analysis. The subject of our
      manuscript, the graphical user interface-based Explicet software package, fills a
      previously unmet need for a robust, yet intuitive means of integrating the
      outputs of the software pipelines with user-specified metadata and then
      visualizing the combined data.

PMID- 24021388
TI  - Reply from author re: J. Kellogg Parsons. High-intensity focused ultrasound for
      prostate cancer: tempering our enthusiasm. Eur Urol 2014;65:915-6: High-intensity
      focused ultrasound for prostate cancer: feeding our enthusiasm.

PMID- 24021387
TI  - International expert consensus statement: Percutaneous transluminal renal
      denervation for the treatment of resistant hypertension.
AB  - Catheter-based radiofrequency ablation technology to disrupt both efferent and
      afferent renal nerves has recently been introduced to clinical medicine after the
      demonstration of significant systolic and diastolic blood pressure reductions.
      Clinical trial data available thus far have been obtained primarily in patients
      with resistant hypertension, defined as standardized systolic clinic blood
      pressure >= 160 mm Hg (or >= 150 mm Hg in patients with type 2 diabetes) despite
      appropriate pharmacologic treatment with at least 3 antihypertensive drugs,
      including a diuretic agent. Accordingly, these criteria and blood pressure
      thresholds should be borne in mind when selecting patients for renal nerve
      ablation. Secondary forms of hypertension and pseudoresistance, such as
      nonadherence to medication, intolerance of medication, and white coat
      hypertension, should have been ruled out, and 24-h ambulatory blood pressure
      monitoring is mandatory in this context. Because there are theoretical concerns
      with regard to renal safety, selected patients should have preserved renal
      function, with an estimated glomerular filtration rate >= 45 ml/min/1.73 m(2).
      Optimal periprocedural management of volume status and medication regimens at
      specialized and experienced centers equipped with adequate infrastructure to cope
      with potential procedural complications will minimize potential patient risks.
      Long-term safety and efficacy data are limited to 3 years of follow-up in small
      patient cohorts, so efforts to monitor treated patients are crucial to define the
      long-term performance of the procedure. Although renal nerve ablation could have
      beneficial effects in other conditions characterized by elevated renal
      sympathetic nerve activity, its potential use for such indications should
      currently be limited to formal research studies of its safety and efficacy.

PMID- 24021389
TI  - The ex-Gaussian distribution of reaction times in adolescents with attention
      deficit/hyperactivity disorder.
AB  - We investigated the three parameters (mu, sigma, tau) of ex-Gaussian distribution
      of RT derived from the Conners' continuous performance test (CCPT) and examined
      the moderating effects of the energetic factors (the inter-stimulus intervals
      (ISIs) and Blocks) among these three parameters, especially tau, an index
      describing the positive skew of RT distribution. We assessed 195 adolescents with
      DSM-IV ADHD, and 90 typically developing (TD) adolescents, aged 10-16.
      Participants and their parents received psychiatric interviews to confirm the
      diagnosis of ADHD and other psychiatric disorders. Participants also received
      intelligence (WISC-III) and CCPT assessments. We found that participants with
      ADHD had a smaller mu, and larger tau. As the ISI/Block increased, the magnitude
      of group difference in tau increased. Among the three ex-Gaussian parameters, tau
      was positively associated with omission errors, and mu was negatively associated
      with commission errors. The moderating effects of ISIs and Blocks on tau
      parameters suggested that the ex-Gaussian parameters could offer more information
      about the attention state in vigilance task, especially in ADHD.

PMID- 24021390
TI  - Plantar pressure patterns in women affected by Ehlers-Danlos syndrome while
      standing and walking.
AB  - This study aims to quantitatively characterize plantar pressure distribution in
      women affected by Ehlers-Danlos syndrome of the hypermobile type (EDS-HT) to
      verify the existence of peculiar patterns possibly related to postural anomalies
      or physical and functional lower limb impairments typical of this disease. A
      sample of 26 women affected by EDS-HT (mean age 36.8, SD 12.0) was tested using a
      pressure platform in two conditions, namely static standing and walking. Raw data
      were processed to assess contact area and mean and peak pressure distribution in
      rearfoot, midfoot and forefoot. Collected data were then compared with those
      obtained from an equally numbered control group of unaffected women matched for
      age and anthropometric features. The results show that, in both tested
      conditions, women with EDS-HT exhibited significantly smaller forefoot contact
      areas and higher peak and mean pressure than the control group. No differences in
      the analyzed parameters were found between right and left limb. The findings of
      the present study suggest that individuals with EDS-HT are characterized by
      specific plantar pressure patterns that are likely to be caused by the
      morphologic and functional foot modification associated with the syndrome. The
      use of electronic pedobarography may provide physicians and rehabilitation
      therapists with information useful in monitoring the disease's progression and
      the effectiveness of orthotic treatments. 

PMID- 24021391
TI  - Trends in the prevalence of childhood disability: analysis of data from the
      national disability registry of Taiwan, 2000-2011.
AB  - Childhood disability is not uncommon, but data at the national level are limited,
      especially those on the changes in the prevalence over time. On the basis of the
      Disabled Welfare Act, Taiwan began to certify disabled residents and provide
      various services in 1980. All the cases receiving services are registered, and
      the registry provides a rare opportunity for studying childhood disability at the
      national level. Using the data from 2000 to 2011, we calculated the age-specific
      prevalence of all disability combined and assessed the changes over time. We also
      calculated the prevalence rate and the proportion in all disabilities combined
      for each disability category and assessed the trends. As certification before 3
      years old is generally discouraged by the government, we limited analyses to
      children between 3 and 17 years old. We found that the registered cases ranged
      from 49,242 to 61,717 from 2000 to 2011 and that intellectual disability (ID),
      had been the leading category all through the years. The proportion of autism
      spectrum disorders (ASD) had been increasing rapidly and become the third leading
      disability in 2011. The prevalence of all disabilities combined increased
      constantly from 9.98/1000 to 15.41/1000 (p<0.01), and increases were generally
      observed every year in all age groups (p<0.01). The increase could largely be
      attributable to the increases in ID and ASD, while the increasing trends were
      also significant in "multiple disabilities," "speech or language impairment," and
      "other disabilities listed by the Department of Health" (p<0.01 for all the five
      categories). An increase with age in the prevalence of all disabilities combined
      could be observed all through the years (p<0.01 in all calendar years). We
      concluded that the prevalence of childhood disability has been increasing in
      Taiwan, with ID contributing the most cases and ASD as an emerging problem.
      However, the increase of prevalence cannot be attributed entirely to the increase
      in the occurrence of cases, and an increase in the proportion of cases registered
      was an more important factor, which may be in turn attributable to a better
      service of the related agencies, lower discrimination against the patients,
      higher awareness of the disorder, and more willingness of the guardians to
      register. 

PMID- 24021392
TI  - Understanding goals and intentions in low-functioning autism.
AB  - We investigated ability to understand goals and attribute intentions in the
      context of two imitation studies in low-functioning, nonverbal children with
      autism (L-F CWA), a population that is rarely targeted by research in the domain.
      Down syndrome children (DSC) and typically developing children (TDC) were
      recruited to form matched comparison groups. In the two sets of simple action
      demonstrations only contextual indicators of the model's intentions were
      manipulated. In the Head touch experiment the model activated a button on a toy
      by pushing it with the forehead, whereas in the Hidden box experiment the model
      used a ball with a magnet to lift a box out of its container. Both actions were
      unusual and non-affordant with regards to the objects involved, none of the
      children in the baseline condition produced them. L-F CWA imitated the
      experimenter exactly, regardless of the model's intention. TDC showed
      appreciation of the model's intention by imitating her actions selectively. DSC
      reproduced only the intentional action as often as they imitated the experimenter
      exactly. It is concluded that L-F CWA attributed goals to the observed model, but
      did not show an appreciation of the model's intentions even in these simplified,
      nonverbal contexts. 

PMID- 24021393
TI  - A multi-component universal intervention to improve diet and physical activity
      among adults with intellectual disabilities in community residences: a cluster
      randomised controlled trial.
AB  - People with ID have an increased risk for unhealthy diets, physical inactivity
      and weight disturbances. The aim of the current study was to investigate the
      effectiveness of a novel and complex intervention to improve diet and physical
      activity, targeting both caregivers and residents, in community residences for
      people with ID. A three component intervention based on Social Cognitive Theory
      was developed, including: (1) appointment of a health ambassador in each
      community residence attending network meetings, (2) a study circle for
      caregivers, and (3) a health course for the residents. The intervention lasted
      for 12-16 months and allowed for some local tailoring. A cluster randomised
      controlled trial, randomised at residence level, was conducted to evaluate the
      effects of the intervention. Thirty community residences for people with mild or
      moderate ID in Stockholm County, Sweden, were included. A total of 130
      participants, 74 women and 56 men aged 20-66 years, entered, and 129 participants
      completed the study. The primary outcome was physical activity, measured by
      pedometry. Secondary outcomes were BMI, waist circumference, dietary quality
      measured by digital photography, satisfaction with life assessed with a scale,
      and work routines assessed with a questionnaire. Outcomes were related to
      intervention fidelity. A positive intervention effect was found on physical
      activity, with an average increase of 1608 steps/day among participants in the
      intervention group (P=0.045). The effect size was 0.29 (Cohen's d). The type of
      residence was found to be an effect moderator. A positive intervention effect was
      found as well on work routines, with an average increase of 7.1 percentage points
      on a self-assessment scale among residences in the intervention group (P=0.016).
      No significant effects were found on BMI, waist circumference, dietary quality,
      or satisfaction with life. In conclusion, this innovative intervention was
      effective in improving physical activity and work routines. It is likely that
      even greater effects could be achieved by improvements in implementation
      strategies, leading to higher fidelity. 

PMID- 24021394
TI  - Impaired implicit sequence learning in children with developmental dyslexia.
AB  - It has been proposed that an impairment of procedural memory underlies a range of
      linguistic, cognitive and motor impairments observed in developmental dyslexia
      (DD). However, studies designed to test this hypothesis using the implicit
      sequence learning paradigm have yielded inconsistent results. A fundamental
      aspect of procedural learning is that it takes place over an extended time-period
      that may be divided into distinct stages based on both behavioural
      characteristics and neural correlates of performance. Yet, no study of implicit
      sequence learning in children with DD has included learning stages beyond a
      single practice session. The present study was designed to fill this important
      gap by extending the investigation to include the effects of overnight
      consolidation as well as those of further practice on a subsequent day. The
      results suggest that the most pronounced procedural learning impairment in DD may
      emerge only after extended practice, in learning stages beyond a single practice
      session. 

PMID- 24021395
TI  - Surgical mortality - an analysis of all deaths within a general surgical
      department.
AB  - BACKGROUND: Post-operative mortality is one of the most universal and important
      outcomes that can be measured in surgical practice and is increasingly used to
      measure quality of care. The aim of this study was to evaluate overall mortality
      within a surgical department and to analyse factors associated with operative and
      non-operative death. METHODS: We analysed prospectively collected data detailing
      all surgical admissions, procedures and mortalities over a twelve year period
      (2000-2012) from a regional Irish hospital. We evaluated type of operation,
      patient factors and cause of death. RESULTS: A total of 62 085 patients were
      admitted under surgical care between the 1st of January 2000 and the 31st of
      December 2011. There were a total of 578 deaths during this period (0.93% overall
      mortality rate). 415 deaths (71.8%) occurred in non-operative patients in which
      advanced cancer (36.5%), sepsis (14.9%), cardiorespiratory failure (13.2%) and
      trauma (11%) were the primary causes. A total of 22 788 surgical procedures were
      performed with an operative mortality rate of 0.71%. Mortality rate following
      elective surgery was 0.17% and following emergency surgery was 10-fold higher
      (1.7%). The main cause of post-operative death was sepsis (30.02%). Emergency
      operations, increasing age and major procedures significantly increased mortality
      risk (p < 0.001). CONCLUSION: Post-operative deaths comprise a small proportion
      of overall deaths within a surgical service. Mortality figures alone are not an
      accurate representation of surgical performance but in the absence of other
      easily available quality outcome measures they can be used as a surrogate marker
      when all confounding factors are accounted for.

PMID- 24021396
TI  - Haplodiploidy and the evolution of eusociality: worker reproduction.
AB  - Hamilton's haplodiploidy hypothesis suggests that the relatively higher
      relatedness of full sisters in haplodiploid populations promotes altruistic sib
      rearing and, consequently, the evolution of eusociality. This haplodiploidy
      effect works when some broods have a relatively female-biased sex ratio and other
      broods have a relatively male-biased sex ratio, termed split sex ratios. There is
      empirical evidence for two scenarios having potentially led to split sex ratios
      en route to eusociality: unmated queens and queen replacement. A recent analysis
      of these two scenarios has suggested that haplodiploidy can either promote or
      inhibit the evolution of eusociality and that the effect is usually small.
      However, this work made the simplifying assumptions that there is only negligible
      reproduction by workers and that their offspring have the same sex ratio as those
      produced by the queen. Here, we relax these assumptions and find that worker
      reproduction has a negative influence on the evolution of helping, either
      reducing the extent to which it is promoted or leading to it being inhibited.
      This is particularly so when workers are unmated and hence constrained to produce
      only sons, by arrhenotoky. Overall, when parameterized with empirical data, our
      results suggest that split sex ratios in haplodiploid species have not played an
      important role in facilitating the evolution of eusociality.

PMID- 24021397
TI  - Evolution of manipulated behavior.
AB  - Many social behaviors are triggered by social partners. For example, cells in a
      multicellular organism often become soma via extrinsically regulated
      differentiation, while individuals in a eusocial colony often become helpers via
      extrinsic caste determination. One explanation for social triggering is that it
      informs when it is beneficial to express the behavior. Alternatively, social
      triggering can represent manipulation where social partners partially or
      completely control the focal individual's behavior. For instance, caste
      determination in primitively eusocial taxa is typically accomplished via
      differential feeding or dominance hierarchies, suggesting some manipulation.
      However, selection would favor resistance if manipulation is detrimental to
      manipulated parties, and the outcome of the manipulation conflict remains
      intricate. We analyze the coevolution of manipulation and resistance in a simple
      but general setting. We show that, despite possible resistance, manipulated
      behavior can be established under less stringent conditions than spontaneous
      (i.e., nonmanipulated) behavior because of resistance costs. The existence of
      this advantage might explain why primitive eusocial behavior tends to be
      triggered socially and coercively. We provide a simple condition for the
      advantage of manipulated behavior that may help infer whether a socially
      triggered behavior is manipulated. We illustrate our analysis with a hypothetical
      example of maternal manipulation relevant to primitive eusociality.

PMID- 24021398
TI  - Predicting the effect of urban noise on the active space of avian vocal signals.
AB  - Urbanization changes the physical environment of nonhuman species but also
      markedly changes their acoustic environment. Urban noise interferes with acoustic
      communication in a range of animals, including birds, with potentially profound
      impacts on fitness. However, a mechanistic theory to predict which species of
      birds will be most affected by urban noise is lacking. We develop a mathematical
      model to predict the decrease in the active space of avian vocal signals after
      moving from quiet forest habitats to noisy urban habitats. We find that the
      magnitude of the decrease is largely a function of signal frequency. However,
      this relationship is not monotonic. A metaregression of observed increases in the
      frequency of birdsong in urban noise supports the model's predictions for signals
      with frequencies between 1.5 and 4 kHz. Using results of the metaregression and
      the model described above, we show that the expected gain in active space
      following observed frequency shifts is up to 12% and greatest for birds with
      signals at the lower end of this frequency range. Our generally applicable model,
      along with three predictions regarding the behavioral and population-level
      responses of birds to urban noise, represents an important step toward a theory
      of acoustic communication in urban habitats.

PMID- 24021399
TI  - Responses of social and solitary bees to pulsed floral resources.
AB  - Pulsed food resources lead to mismatches between distribution of consumers and
      resources in space and time. Many studies have investigated how pollinators and
      floral resources covary in space, but few have looked at their covariance among
      years. I studied responses of two bee taxa, Bombus (a social genus) and
      Anthophora (a solitary genus), to variation in flowering by Astragalus
      scaphoides, a perennial herb that flowers in alternate years. First, I quantified
      the rate at which individual plants were visited by bees. Anthophora showed
      evidence of a demographic response to resource pulses--that is, more individuals
      were seen in the year after a high-flowering year--whereas Bombus did not.
      Second, I quantified pollinator behavior by following individual bees and
      recording the proportion of visits to A. scaphoides within single foraging bouts.
      The proportion of visits to A. scaphoides by both taxa increased with A.
      scaphoides's flowering density. Higher specialization in high-flowering years
      likely makes both taxa better pollinators in high-flowering years. If these taxa
      differ in effectiveness as pollinators, then these responses translate into
      variation in pollination services in space and time, specifically, more activity
      by Bombus in high-flowering years and more by Anthophora in years following high
      flowering years. They also emphasize that pollinator activity depends in part on
      past-as well as current-floral resources.

PMID- 24021400
TI  - Observed fitness may affect niche overlap in competing species via selective
      social information use.
AB  - Social information transmission is important because it enables horizontal spread
      of behaviors, not only between conspecifics but also between individuals of
      different species. Because interspecific social information use is expected to
      take place among species with similar resource needs, it may have major
      consequences for the emergence of local adaptations, resource sharing, and
      community organization. Social information use is expected to be selective, but
      the conditions promoting it in an interspecific context are not well known. Here,
      we experimentally test whether pied flycatchers (Ficedula hypoleuca) use the
      clutch size of great tits (Parus major) in determining the quality of the
      observed individual and use it as a basis of decision making. We show that pied
      flycatchers copied or rejected a novel nest site feature preference of great tits
      experimentally manipulated to exhibit high or low fitness (clutch size),
      respectively. Our results demonstrate that the social transmission of behaviors
      across species can be highly selective in response to observed fitness, plausibly
      making the phenomenon adaptive. In contrast with the current theory of species
      coexistence, overlap between realized niches of species could dynamically
      increase or decrease depending on the observed success of surrounding
      individuals.

PMID- 24021401
TI  - The geographic mosaic of sex and infection in lake populations of a New Zealand
      snail at multiple spatial scales.
AB  - Understanding how sexual and asexual forms of the same species coexist is a
      challenge for evolutionary biology. The Red Queen hypothesis predicts that sex is
      favored by parasite-mediated selection against common asexual genotypes, leading
      to the coexistence of sexual and asexual hosts. In a geographic mosaic, where the
      risk of infection varies in space, the theory also predicts that sexual
      reproduction would be positively correlated with disease prevalence. We tested
      this hypothesis in lake populations of a New Zealand freshwater snail,
      Potamopyrgus antipodarum, by comparing pairwise difference matrices for infection
      frequency and male frequency using partial Mantel tests. We conducted the test at
      three spatial scales: among lakes on the South Island, among depths within an
      intensively sampled lake (Lake Alexandrina), and within depths at Lake
      Alexandrina. We found that the difference in infection risk and the difference in
      the proportion of sexual snails were significantly and positively correlated at
      all spatial scales. Our results thus suggest that parasite-mediated selection
      contributes to the long-term coexistence of sexual and asexual individuals in
      coevolutionary hotspots, and that the "warmth" of hotspots can vary on small
      spatial scales.

PMID- 24021402
TI  - Viral substitution rate variation can arise from the interplay between within
      host and epidemiological dynamics.
AB  - The evolutionary rates of RNA viruses can differ from one another by several
      orders of magnitude. Much of this variation has been explained by differences in
      viral mutation rates and selective environments. However, substitution rates also
      vary considerably across viral populations belonging to the same species. In
      particular, viral lineages from epidemic regions tend to have higher substitution
      rates than those from endemic regions, and lineages from populations with higher
      contact rates tend to have higher substitution rates than those from populations
      with lower contact rates. We address the mechanism behind these patterns by using
      a nested modeling approach, whereby we integrate within-host viral replication
      dynamics with a population-level epidemiological model. Through numerical
      simulations and analytical approximations, we show that variation in viral
      substitution rates over the course of an infection, coupled with differences in
      age of infection of transmitting hosts under different epidemiological scenarios,
      can explain these evolutionary patterns. We further derive analytical estimates
      of expected substitution rate differences under epidemic versus endemic
      epidemiological conditions. By comparing these estimates to empirical data for
      four viral species, we show that these factors are sufficient to explain observed
      variation in substitution rates in three of four cases. This work shows that even
      in neutrally evolving viral populations, epidemiological dynamics can alter
      substitution rates via the interplay between within-host replication dynamics and
      population-level disease dynamics.

PMID- 24021403
TI  - Multiple sexual signals and behavioral reproductive isolation in a diverging
      population.
AB  - Sexual trait divergence has been shown to play a role in the evolution of
      reproductive isolation. While variation in multiple sexual signals is common
      among closely related species, little is known about the role of these different
      axes of phenotype variation with respect to the evolution of behavioral
      reproductive isolation. Here we study a unique population of barn swallows
      (Hirundo rustica transitiva) that can be distinguished phenotypically from its
      neighboring populations only on the basis of two features of male plumage:
      exaggerated expression of both long tail streamers and dark ventral coloration.
      Using phenotype manipulation experiments, we conducted a paternity study to
      examine whether both traits are sexually selected. Our results show that an
      exaggerated form of the local male phenotype (with both tail elongation and color
      darkening) is favored by local females, whereas males whose phenotypes were
      manipulated to look like males of neighboring subspecies suffered paternity
      losses from their social mates. These results confirm the multiple signaling role
      of the unique tail and color combination in our diverging population and suggest
      a novel possibility according to which multiple sexual signals may also be used
      to discriminate among males from nearby populations when prezygotic reproductive
      isolation is adaptive.

PMID- 24021404
TI  - A life-history approach to the late Pleistocene megafaunal extinction.
AB  - A major criticism of the "overkill" theory for the late Pleistocene extinction in
      the Americas has been the seeming implausibility of a relatively small number of
      humans selectively killing off millions of large-bodied mammals. Critics argue
      that early Paleoindian hunters had to be extremely selective to have produced the
      highly size-biased extinction pattern characteristic of this event. Here, we
      derive a probabilistic extinction model that predicts the extinction risk of
      mammals at any body mass without invoking selective human harvest. The new model
      systematically analyzes the variability in life-history characteristics, such as
      the instantaneous mortality rate, age of first reproduction, and the maximum net
      reproductive rate. It captures the body size-biased extinction pattern in the
      late Pleistocene and precisely predicts the percentage of unexpectedly persisting
      large mammals and extinct small ones. A test with a global late Quaternary mammal
      database well supports the model. The model also emphasizes that quantitatively
      analyzing patterns of variability in ecological factors can shed light on diverse
      behaviors and patterns in nature. From a macro-scale conservation perspective,
      our model can be modified to predict the fate of biota under the pressures from
      both climate change and human impacts.

PMID- 24021405
TI  - Social factors driving settlement and relocation decisions in a solitary and
      aggregative spider.
AB  - Both ecological and social factors play an important role in determining the
      structure of animal settlement patterns. While the ecological factors determining
      animal settlement are generally well known, the relative importance of social
      factors in mediating fine-scale settlement choices is poorly understood. As a
      result, we have little knowledge of why individuals choose to settle near
      specific neighbors. Here we used a web-building spider (Nephila plumipes) that
      settles both solitarily and next to neighbors within aggregations to examine the
      specific social factors that influence settlement decisions. Within experimental
      enclosures, we observed the settlement patterns of females pre- and postmale
      release. This allowed us to compare two models of aggregative settlement in
      lekking species-the hotshot and preferences models-to examine the relative
      importance of a female's phenotype and mate attraction to further dissect
      settlement and relocation decisions. We show that mate attraction increased with
      aggregation size and that larger females were generally preferred, supporting
      both the hotshot and preference models of aggregative settlement. We further
      demonstrate that smaller females that attracted fewer males within an aggregation
      were most likely to relocate. Our results demonstrate how social feedback can
      affect initially state-dependent settlement decisions, thereby highlighting the
      dynamic nature of settlement.

PMID- 24021406
TI  - Surviving in sympatry: paragenital divergence and sexual mimicry between a pair
      of traumatically inseminating plant bugs.
AB  - Reproductive interactions between species can carry significant costs (e.g.,
      wasted time, energy, and gametes). In traumatically inseminating insects,
      heterospecific mating costs may be intensified, with indiscriminate mating and
      damaging genitalia leading to damage or death. When closely related traumatically
      inseminating species are sympatric, we predict selection should favor the rapid
      evolution of reproductive isolation. Here we report on a cryptic species of
      traumatically inseminating plant bug, Coridromius taravao, living sympatrically
      with its sister species, Coridromius tahitiensis, in French Polynesia. Despite
      their sister-species relationship, they exhibit striking differences in
      reproductive morphology, with females of each species stabbed and inseminated
      through different parts of their abdomens. Furthermore, C. tahitiensis is
      sexually dimorphic in coloration and vestiture, while both sexes of C. taravao
      share the C. tahitiensis male expression of these traits. These findings support
      a role for (1) reproductive character divergence and (2) interspecies sexual
      mimicry in limiting interspecific mating brought about by indiscriminate male
      mating behavior.

PMID- 24021407
TI  - An analytical framework for estimating fertilization bias and the fertilization
      set from multiple sperm-storage organs.
AB  - How sperm from competing males are used to fertilize eggs is poorly understood
      yet has important implications for postcopulatory sexual selection. Sperm may be
      used in direct proportion to their numerical representation within the
      fertilization set or with a bias toward one male over another. Previous
      theoretical treatments have assumed a single sperm-storage organ, but many taxa
      possess multiple organs or store sperm within multiple regions of the
      reproductive tract. In Drosophila, females store sperm in two distinct storage
      organ types: the seminal receptacle (SR) and the paired spermathecae. Here, we
      expand previous "raffle" models to describe "fertilization bias" independently
      for sperm within the SR and the spermathecae and estimate the fertilization set
      based on the relative contribution of sperm from the different sperm-storage
      organ types. We apply this model to three closely related species to reveal rapid
      divergence in the fertilization set and the potential for female sperm choice.

PMID- 24021408
TI  - The evolution of natural competence: disentangling costs and benefits of sex in
      bacteria.
AB  - One of the most challenging questions in evolutionary biology is how sex has
      evolved in the face of substantial fitness costs. In this study, we focus on the
      evolution of bacterial sex in the form of natural transformation, where cells
      take up exogenous DNA and integrate it into the genome. Besides the physiological
      cost of producing a DNA uptake system, transformation can potentially impose a
      genetic cost as a result of an overrepresentation of deleterious mutations in the
      extracellular DNA pool. On the other hand, the uptake of DNA can be beneficial
      not only because of genetic effects but also because of the immediate nutritional
      value of the DNA. To disentangle these fitness costs and benefits, we developed a
      mathematical model and competed three bacterial types during adaptation to a new
      environment: competent cells capable of DNA import and digestion; competent cells
      capable of DNA import, digestion, and recombination; and noncompetent cells. Our
      results indicate a complex interplay between several physiological and ecological
      factors, including the rate at which DNA is taken up, the rate of DNA decay in
      the medium, and the nutritional value of DNA. In finite populations, the
      recombining type is often favored through the Fisher-Muller effect.

PMID- 24021409
TI  - Evolutionary branching in complex landscapes.
AB  - Divergent adaptation to different environments can promote speciation, and it is
      thus important to consider spatial structure in models of speciation. Earlier
      theoretical work, however, has been limited to particularly simple types of
      spatial structure (linear environmental gradients and spatially discrete
      metapopulations), leaving unaddressed the effects of more realistic patterns of
      landscape heterogeneity, such as nonlinear gradients and spatially continuous
      patchiness. To elucidate the consequences of such complex landscapes, we adapt an
      established spatially explicit individual-based model of evolutionary branching.
      We show that branching is most probable at intermediate levels of various types
      of heterogeneity and that different types of heterogeneity have, to some extent,
      additive effects in promoting branching. In contrast to such additivity, we find
      a novel refugium effect in which refugia in hostile environments provide
      opportunities for colonization, thus increasing the probability of branching in
      patchy landscapes. Effects of patchiness depend on the scale of patches relative
      to dispersal. Providing a needed connection to empirical research on biodiversity
      and conservation policy, we introduce empirically accessible spatial
      environmental metrics that quantitatively predict a landscape's branching
      propensity.

PMID- 24021410
TI  - Increased levels of IL-17A in patients with fibromyalgia.
AB  - OBJECTIVES: The aim of this study was to evaluate the plasma levels of IL-17A in
      fibromyalgia patients, and to look for any correlations between this data and the
      concentrations of some pro- and anti-inflammatory cytokines. METHODS: We
      performed a study including 58 fibromyalgia patients and 39 healthy women matched
      for age and body mass index. The plasma levels of IL-17A and other pro- and anti
      inflammatory cytokines were measured by using the technique of cytometric bead
      array (CBA). The analysis of differences between groups was performed using Mann
      Whitney test and the analysis of the correlations by Spearman's correlation test.
      RESULTS: The analyses showed that fibromyalgia patients present increased levels
      of IL-17A. They also revealed that plasma concentrations of IL17A positively
      correlate with levels of IL-2, IL-4 and IL-10, TNF and IFNgamma. CONCLUSIONS: As
      far as we are aware, this is the first study to demonstrate increased levels of
      IL17A in fibromyalgia patients. The positive correlation between the levels of IL
      17A and of other cytokines strengthens the hypothesis of the involvement of
      inflammatory mechanisms in the development of this syndrome.

PMID- 24021411
TI  - Harvesting energy of interaction between bacteria and bacteriophage in a membrane
      less fuel cell.
AB  - When a fuel and oxidant flow in laminar contact through a micro-fluidic channel,
      a sharp interface appears between the two liquids, which eliminate the need of a
      proton exchange membrane. This principle has been used to generate potential in a
      membrane-less fuel cell. This study use such a cell to harvest energy of
      interaction between a bacteria having negative charge on its surface and a
      bacteriophage with positive and negative charges on its tail and head,
      respectively. When Klebsiella pneumoniae (Kp6) and phage (P-Kp6) are pumped
      through a fuel cell fitted with two copper electrodes placed at its two sides,
      interaction between these two charged species at the interface results in a
      constant open circuit potential which varies with concentration of charged
      species but gets generated for both specific and non-specific bacteria and phage
      system. Oxygenation of bacteria or phage however diminishes the potential unlike
      in conventional microbial fuel cells. 

PMID- 24021412
TI  - Crush cytology of a primary intraspinal rhabdoid papillary meningioma: a case
      report.
AB  - BACKGROUND: Both rhabdoid and papillary meningioma are rare variants of
      meningioma categorized as WHO grade III. Here, we report a rare case of combined
      rhabdoid papillary meningioma with discussion of its differential intraoperative
      cytologic diagnoses. CASE: The patient was a 72-year-old female who presented
      with a huge mass at the cervical spine on MRI. The crush smears showed a radially
      arranged pattern of elongated tumor cells centered around the vessels, which
      formed a pseudorosette-like papillary structure, as well as singly scattered
      large gemistocyte-like rhabdoid cells with distinct cell borders. Rhabdoid cells
      had eccentrically placed vesicular nuclei with plump, fibrillary-to-hyaline
      cytoplasm with short broad processes. Nuclei had occasional nuclear inclusions
      with no nuclear grooves. CONCLUSION: Rhabdoid papillary meningiomas, encountered
      less often, should be distinguished from metastatic tumors of rhabdoid or
      papillary configuration, astrocytomas, ependymomas and atypical teratoid/rhabdoid
      tumor. Search for eosinophilic hyaline cytoplasm, rather than a fibrillary one,
      is critical for distinguishing it from other commonly encountered spinal cord
      tumors in the total absence of meningothelial whorls, like the present case. We
      also emphasize that the present case is the first case of rhabdoid papillary
      meningioma with primary manifestation in the spinal cord.

PMID- 24021413
TI  - The usefulness of triple layers suturing technique with frilled pectoralis major
      musculocutaneous flap for pharyngocutaneous fistula.

PMID- 24021414
TI  - Organochlorine contaminants in different tissues from Platichthys flesus (Pisces,
      Pleuronectidea).
AB  - Polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) are organic
      contaminants that tend to accumulate in fish. Estuaries are exposed to high
      anthropogenic activities, therefore tending to accumulate more contaminants than
      the adjacent coastal waters. Platichthys flesus, a fish with high economic value,
      was analysed for PCBs and HCB along its different age groups, in liver, gills,
      gonads and muscle. Younger fishes were caught in the estuary, whereas older
      fishes were caught in the adjacent coastal waters and acquired at Figueira da Foz
      Regional Office of Docapesca-Portos e Lotas, SA. Both contaminants concentrations
      follow the pattern: liver>gills>muscle. Hepatosomatic index had the lowest values
      in younger fishes and the highest values in older fishes. Condition factor values
      remain stable with age. Younger fishes had higher PCBs concentrations than the
      older fishes. In opposition HCB was only detected in fish from 3+ to 5+ and its
      concentration tended to increase with age. Overall P. flesus is considered safe
      for human intake. 

PMID- 24021415
TI  - Toxic effects of imidazolium-based ionic liquids on Caenorhabditis elegans: the
      role of reactive oxygen species.
AB  - By using Caenorhabditis elegans (C. elegans) as a model animal, the present work
      is aimed to evaluate the acute toxicity of imidazolium-based bromide Ionic
      Liquids (ILs), and to elucidate the underlying mechanisms involved. Firstly, 24-h
      median lethal concentration (LC50) for eight ILs with different alkyl chain
      lengths and one or two methyl groups in the imidazolium ring were determined to
      be in a range of 0.09-6.64 mg mL(-1). Four ILs were selected to investigate the
      toxic mechanisms. Mortality, levels of reactive oxygen species (ROS), lipofuscin
      accumulation and expression of superoxide dismutase 3 in C. elegans were
      determined after exposed to ILs at sub-lethal concentrations for 12h. A
      significant increase in the levels of these biomarkers was observed in accordance
      with the results of 12-h lethality assay. The addition of 0.5% dimethyl
      sulfoxide, which acts as a radical scavenger, remarkably rescued the lethality of
      C. elegans and significantly decreased the ROS level in C. elegans. Our results
      suggest that ROS play an important role in IL-induced toxicity in C. elegans.

PMID- 24021416
TI  - Research methodologies in informed consent studies involving surgical and
      invasive procedures: time to re-examine?
AB  - OBJECTIVE: We conducted a review of informed consent studies involving surgical
      and invasive procedures and report the degree to which current research targets a
      broader scope of patient outcomes beyond comprehension. METHODS: Using PubMed,
      Cumulative Index to Nursing and Allied Health Literature, and Excerpta Medical
      Database, we identified 97 articles for review. Six members coded articles and
      generated scores of study design quality. RESULTS: The mean quality score (10.7
      out of a total score of 20) was low. Most studies were single institution-based,
      relying on one-time data collections. Randomly assigning subjects to study
      conditions, using power analysis to determine subject numbers, and reporting
      psychometric evidence, such as reliability and validity, were not widely
      reported. Most frequently targeted patient outcomes were knowledge, understanding
      and satisfaction. Core informed consent outcomes (e.g. capacity, voluntariness,
      decision making) and emotional factors (e.g. anxiety) were not extensively
      addressed. CONCLUSION: Informed consent research may benefit from applying
      qualitative methods to more directly tap into patients' beliefs and decisions by
      eliciting in patients' own words their emotions and reasoning around processing
      informed consent content. PRACTICE IMPLICATIONS: Research that addresses patient
      perspectives toward surgical interventions should tap into underexplored ethical
      and emotional factors that shape decision making.

PMID- 24021417
TI  - Social support and glycemic control in type 2 diabetes: a systematic review of
      observational studies.
AB  - OBJECTIVE: We aim to systematically review observational studies examining the
      association between social support and glycemic control in adults with type 2
      diabetes. METHODS: We searched MEDLINE, PsycINFO, EMBASE, Scopus, Web of Science
      and Sociological Abstracts to July 2012 for observational studies investigating
      the association between structural or functional aspects of social support
      (social networks, community ties, marital status, family support, perceived,
      actual, emotional or instrumental social support) and glycemic control (HbA1c).
      RESULTS: From electronic and reference searches, 29 studies were eligible. Twenty
      different assessments of social support were used. Family support and composite
      measures of support were most frequently associated with reduced HbA1c. There was
      no evidence for a beneficial effect of other support measures on HbA1c.
      CONCLUSION: We found marked variation in population, setting, measurement of
      social support and definition of outcome, limiting the methodological validity of
      research. Social support may be important in the management of type 2 diabetes,
      the need for consensus and standardization of measures is highlighted. PRACTICE
      IMPLICATIONS: The presence of informal support should be explored in routine
      diabetes care.

PMID- 24021418
TI  - Educational benefits of Internet and computer-based programmes for prostate
      cancer patients: a systematic review.
AB  - OBJECTIVE: This study aims to review systematically the available literature on
      Internet and computer-based patient education programmes, assess the quality of
      these studies and analyze the benefit of these programmes for prostate cancer
      patients. METHODS: Complete databases were searched. Studies were included if
      they concerned patient education of prostate cancer patients, were qualitative or
      quantitative and examined Internet or interactive CD-ROM use. RESULTS: Eighteen
      studies met the inclusion criteria. The majority of the studies reported a
      significant increase in the knowledge of the disease, satisfaction with treatment
      options and support for men. The benefit of the programmes was that the patients
      felt more empowered and obtained a heightened sense of control over their
      disease. CONCLUSION: The Internet or computer-based programmes had a positive
      impact on prostate cancer patient education. Most papers reported that the
      programmes were beneficial, but few presented data from studies with rigorous
      research methodologies to support these claims. PRACTICE IMPLICATIONS: Internet
      and computer-based programmes can be useful tools in prostate cancer patient
      education. In order to improve the benefits of the programmes, more Internet and
      computer-based programmes need to be developed and studied.

PMID- 24021419
TI  - Teen CHAT: Development and utilization of a web-based intervention to improve
      physician communication with adolescents about healthy weight.
AB  - OBJECTIVE: To describe the theoretical basis, use, and satisfaction with Teen
      CHAT, an online educational intervention designed to improve physician-adolescent
      communication about healthy weight. METHODS: Routine health maintenance
      encounters between pediatricians and family practitioners and their overweight
      adolescent patients were audio recorded, and content was coded to summarize
      adherence with motivational interviewing techniques. An online educational
      intervention was developed using constructs from social cognitive theory and
      using personalized audio recordings. Physicians were randomized to the online
      intervention or not, and completed post-intervention surveys. RESULTS: Forty-six
      physicians were recruited, and 22 physicians were randomized to view the
      intervention website. The educational intervention took an average of 54min to
      complete, and most physicians thought it was useful, that they would use newly
      acquired skills with their patients, and would recommend it to others. Fewer
      physicians thought it helped them address confidentiality issues with their
      adolescent patients. CONCLUSION: The Teen CHAT online intervention shows
      potential for enhancing physician motivational interviewing skills in an
      acceptable and time-efficient manner. PRACTICE IMPLICATIONS: If found to be
      effective in enhancing motivational interviewing skills and changing adolescent
      weight-related behaviors, wide dissemination will be feasible and indicated.

PMID- 24021420
TI  - Prospects for cannabinoid therapies in viral encephalitis.
AB  - Cannabinoids are promising therapies to support neurogenesis and decelerate
      disease progression in neuroinflammatory and degenerative disorders. Whether
      neuroprotective effects of cannabinoids are sustainable during persistent viral
      infection of the CNS is not known. Using a rodent model of chronic viral
      encephalitis based on Borna Disease (BD) virus, in which 1 week treatment with
      the general cannabinoid WIN 55,212-2 has been shown to be neuroprotective
      (Solbrig et al., 2010), we examine longer term (2 week treatment) effects of a
      general (CB1 and CB2) cannabinoid receptor agonist WIN55,212-2 (1mg/kg ip twice
      per day) or a specific (CB2) cannabinoid receptor agonist HU-308 (5mg/kg ip once
      daily) on histopathology, measures of frontostriatal neurogenesis and
      gliogenesis, and viral load. We find that WIN and HU-308 differ in their ability
      to protect new BrdU(+) cells. The selective CB2 agonist HU increases BrdU(+)
      cells in prefrontal cortex (PFC), significantly increases BrdU(+) cells in
      striatum, differentially regulates polydendrocytes vs. microglia/macrophages, and
      reduces immune activation at a time WIN-treated rats appear tolerant to the anti
      inflammatory effect of their cannabinoid treatment. WIN and HU had little direct
      viral effect in PFC and striatum, yet reduced viral signal in hippocampus. Thus,
      HU-308 action on CB2 receptors, receptors known to be renewed during microglia
      proliferation and action, is a nontolerizing mechanism of controlling CNS
      inflammation during viral encephalitis by reducing microglia activation, as well
      as partially limiting viral infection, and uses a nonpsychotropic cannabinoid
      agonist. 

PMID- 24021421
TI  - First detection of Schmallenberg virus in elk (Alces alces) indicating infection
      of wildlife in Bialowieza National Park in Poland.
AB  - Schmallenberg virus (SBV) RNA was detected in the serum of an elk (Alces alces)
      calf captured on the outskirts of Bialowieza National Park (BNP) in December
      2012, and shortly afterwards the calf died of acute bronchopneumonia. Serum
      samples from 169 animals, including bison, red and fallow deer, originating from
      eight locations situated in four Polish Provinces, were tested for the presence
      of SBV-specific antibodies between 2011 and 2013. Although no antibodies were
      found in samples collected up to July 2012, positive samples subsequently
      appeared between November 2012 and January 2013 in all of the sampled regions.
      The introduction of SBV infection to the European bison (Bison bonasus)
      population of BNP between July and November 2012 was also confirmed. 

PMID- 24021422
TI  - hCLCA1 DNA vaccine suppresses cell hyperplasia and mucin expression of goblet
      cells in vitro.
AB  - BACKGROUND: Excessive airway mucus secretion is a remarkable trait of asthma.
      Mucus overproduction mainly resulted from an increase in goblet cell numbers,
      which causes considerable damage to health. However, effective therapeutic
      treatments are still lacking for mucus hypersecretion. Human calcium-activated
      chloride channel 1 (hCLCA1) has been identified to be predominantly responsible
      for mucus hypersecretion. OBJECTIVES: In this study, we investigated the effects
      of an hCLCA1 DNA vaccine on the control of mucus production and goblet cell
      proliferation using an in vitro model goblet cell line (NCI-H292). METHODS: The
      effect of the hCLCA1 DNA vaccine on cell viability and proliferative activity of
      NCI-H292/hCLCA1 was analyzed by electron microscopy, MTT assay, and flow
      cytometry. Expression of mucins and MUC5AC, a major member of the mucin gene
      family in airway goblet cells, was assessed under hCLCA1 DNA vaccine challenges
      by periodic acid-Schiff staining, quantitative real-time PCR and Western blot,
      respectively, and the expression profile of granulocyte-macrophage colony
      stimulating factor (GM-CSF), a critical cytokine in airway inflammation, was also
      examined by real-time PCR and immunocytochemistry. RESULTS: Results showed that
      hCLCA1 overexpression caused high cell proliferation and mucin expression,
      whereas the hCLCA1 DNA vaccine could effectively reverse these abnormal effects.
      In addition, GM-CSF expression was highly induced by hCLCA1 overexpression and
      efficiently suppressed by hCLCA1 DNA vaccine. CONCLUSIONS: These results
      illustrate that the hCLCA1 DNA vaccine effectively inhibits cell hyperplasia and
      mucin gene expression of goblet cells, suggesting that the hCLCA1 DNA vaccine has
      potential value in the treatment of human asthma.

PMID- 24021423
TI  - Time is a crucial factor for the use of oncological treatment for post
      transplantation recurrence of hepatocellular carcinoma.

PMID- 24021424
TI  - Transcription factor NRF2 protects mice against dietary iron-induced liver injury
      by preventing hepatocytic cell death.
AB  - BACKGROUND & AIMS: The liver, being the major site of iron storage, is
      particularly exposed to the toxic effects of iron. Transcription factor NRF2 is
      critical for protecting the liver against disease by activating the transcription
      of genes encoding detoxification/antioxidant enzymes. We aimed to determine if
      the NRF2 pathway plays a significant role in the protection against hepatic iron
      overload. METHODS: Wild-type and Nrf2(-/-) mouse primary hepatocytes were
      incubated with ferric ammonium citrate. Wild-type and Nrf2(-/-) mice were fed
      standard rodent chow or iron-rich diet for 2weeks, with or without daily
      injection of the antioxidant mito-TEMPOL. RESULTS: In mouse hepatocytes, iron
      induced the nuclear translocation of NRF2 and the expression of cytoprotective
      genes in an NRF2-dependent manner. Moreover, Nrf2(-/-) hepatocytes were highly
      susceptible to iron-induced cell death. Wild-type and Nrf2(-/-) mice fed iron
      rich diet accumulated similar amounts of iron in the liver and were equally able
      to increase the expression of hepatic hepcidin and ferritin. Nevertheless, in
      Nrf2-null mice the iron loading resulted in progressive liver injury, ranging
      from mild confluent necrosis to severe necroinflammatory lesions. Hepatocytic
      cell death was associated with gross ultrastructural damage to the mitochondria.
      Notably, liver injury was prevented in iron-fed animals that received mito
      TEMPOL. CONCLUSIONS: NRF2 protects the mouse liver against the toxicity of
      dietary iron overload by preventing hepatocytic cell death. We identify NRF2 as a
      potential modifier of liver disease in iron overload pathology and show the
      beneficial effect of the antioxidant mito-TEMPOL in a mouse model of dietary iron
      induced liver injury.

PMID- 24021425
TI  - Focus.

PMID- 24021427
TI  - Effects of electromagnetic field exposure on the heart: a systematic review.
AB  - The use of electrical devices has gradually increased throughout the last
      century, and scientists have suggested that electromagnetic fields (EMF)
      generated by such devices may have harmful effects on living creatures. This work
      represents a systematic review of collective scholarly literature examining the
      effects of EMFs on the heart. Although most works describing effects of EMF
      exposure have been carried out using city electric frequencies (50-60 Hz), a
      consensus has not been reached about whether long- or short-term exposure to 50
      60 Hz EMF negatively affects the heart. Studies have indicated that EMFs produced
      at cell-phone frequencies cause no-effect on the heart. Differences between
      results of studies may be due to a compensatory response developed by the body
      over time. At greater EMF strengths or shorter exposures, the ability of the body
      to develop compensation mechanisms is reduced and the potential for heart-related
      effects increases. It is noteworthy that diseases of heart tissues such as
      myocardial ischemia can also be successfully treated using EMF. Despite the
      substantial volume of data that has been collected on heart-related effects of
      EMFs, additional studies are needed at the cellular and molecular level to fully
      clarify the subject. Until the effects of EMF on heart tissue are more fully
      explored, electronic devices generating EMFs should be approached with caution. 

PMID- 24021426
TI  - Serum FGF21 increases with hepatic fat accumulation in pediatric onset intestinal
      failure.
AB  - BACKGROUND & AIMS: Previously, FGF21 has been related to glucose and lipid
      metabolism and liver steatosis. Our aim was to evaluate serum FGF21 levels in
      pediatric onset intestinal failure (IF). METHODS: Serum FGF21 was measured in 35
      IF patients at median age of 7.8 years (range 0.2-27) and 59 matched healthy
      controls. Thirty patients underwent liver biopsy. RESULTS: Serum FGF21 levels
      were increased in patients compared to controls [229 pg/ml (21-20,345) vs. 133
      pg/ml (7-1607), p=0.018]. Frequency of liver steatosis (60% vs. 50%, p=0.709) was
      similar during (6/10) and after (10/20) weaning off parenteral nutrition (PN).
      Patients with steatosis had markedly higher serum FGF21 concentration [626 pg/ml
      (21-20,345) vs. 108 pg/ml (32-568), p=0.002] and more advanced liver fibrosis
      [Metavir stage 1.6 (0-4) vs. 0.7 (0-3), p=0.020] without associated inflammation
      or Mallory body formation. Serum FGF21 levels reflected the degree of steatosis
      [FGF21 in grade 3 vs. grades 0-2, p<0.001; grade 1 vs. controls, p=0.002], and
      correlated with steatosis grade (r=0.589, p=0.001). Hepatic steatosis and serum
      FGF21 showed similar associations with duration of PN and remaining small bowel
      length (p<0.05 for all). In a multivariate regression model, liver steatosis
      grade (beta=0.630, p=0.001) predicted serum FGF21 concentration. CONCLUSIONS: In
      pediatric IF increased serum FGF21 levels reflect liver steatosis, while both are
      exclusively associated with duration of PN and extent of small intestinal
      resection. Liver steatosis is coupled with progression of fibrosis without
      accompanying inflammation. Serum FGF21 assay may be useful for diagnosing liver
      steatosis in IF patients.

PMID- 24021428
TI  - Effect of grapefruit juice on amiodarone induced nephrotoxicity in albino rats.
AB  - Amiodarone is a potent antiarrhythmic drug that is used to treat ventricular and
      supraventricular tachyarrhythmias. The present work studied the effect of
      amiodarone on the kidney of albino rats and the possible ameliorative role of
      grapefruit juice. Administration of amiodarone by gastric intubation (18 mg/kg
      body weight (b.w.), daily for 5 weeks) caused many histological alterations
      including intertubular leucocytic infiltrations, degeneration of the renal
      tubules, and atrophy of the glomeruli. Amiodarone caused marked elevation in
      serum creatinine and blood urea nitrogen. Histochemical examination of the renal
      tubules revealed depletion of glycogen and total proteins. Besides, animals
      administered with amiodarone showed an increase of apoptotic bands as detected by
      gel electrophoresis. Treating animals with amiodarone and grapefruit juice (27
      ml/kg b.w.) caused an improvement in histological and histochemical appearance of
      the kidney together with decrease of serum creatinine and blood urea nitrogen.
      Moreover, the apoptosis was decreased. It is concluded from the obtained results
      that grapefruit juice ameliorates the nephrotoxicity of amiodarone in albino rats
      and this may be due to the potent antioxidant effects of its components. 

PMID- 24021430
TI  - Chemoprotective effect of Vernonia amygdalina Del. (Astereacea) against 2
      acetylaminofluorene-induced hepatotoxicity in rats.
AB  - Natural products possessing antioxidant properties play a very crucial role in
      ameliorating deleterious effects of reactive oxygen species. This study
      investigated the chemoprotective properties of methanolic extract of Vernonia
      amygdalina (MEVA) in an experimental model of hepatic oxidative damage induced by
      2-acetylaminofluorene (2-AAF). Rats were divided into six groups. Groups 1 and 2
      received saline and dimethyl sulfoxide, respectively, and served as controls.
      Group 3 received MEVA at a dose of 250 mg/kg, while groups 5 and 6 were
      pretreated for 14 days with MEVA at 250 mg/kg and 500 mg/kg doses before
      coadministration with 2-AAF at 100 mg/kg for another 7 days. 2-AAF was
      administered to group 4 for the last 7 days. Animals were killed 24 h after the
      last administration of 2-AAF. 2-AAF significantly (p < 0.05) induced marked
      hepatic damage as revealed by increased activities of serum enzymes such as
      alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and
      gamma-glutamyl transferase and bilirubin concentration. 2-AAF also elicited
      decrease in the activities of antioxidant enzymes such as superoxide dismutase,
      catalase, glutathione-S-transferase, and glutathione peroxidase, depletion of
      reduced glutathione, and increase in malondialdehyde levels. The activities of
      glucose-6-phosphatase and 5'-nucleotidase were also depleted. MEVA at 250 mg/kg
      and 500 mg/kg significantly (p < 0.05) ameliorated the oxidative damage,
      functional impairments, and histopathological changes associated with 2-AAF
      toxicity by reducing the activities of serum enzymes, upregulating the
      antioxidant defense enzymes and glutathione with decrease in malondialdehyde
      level. In this study, the revealed ameliorative and hepatoprotective effects of
      MEVA against 2-AAF-induced toxicity may be due to its antioxidant and free
      radical scavenging activities, thus suggesting its usefulness as a possible
      chemoprophylactic agent.

PMID- 24021429
TI  - Effects of antioxidants on drugs used against testicular cancer-induced
      alterations in metastasis-associated protein 1 signaling in the rat testis.
AB  - Metastasis-associated protein 1 (MTA1) is involved in tumor growth and metastasis
      of cancers. Being a component of nucleosome remodeling and histone deacetylase
      complex, the protein is also associated with DNA damage response pathway. Since
      the protein is involved in cancer pathology, we first investigated the effects of
      bleomycin, etoposide, and cisplatin (BEP) on MTA1 signaling in the testis.
      Second, since the antioxidants (AOs) have protective effects, we further
      investigated whether or not an AO cocktail modulates the effects of the drugs.
      Adult male Sprague Dawley rats (N = 4) were treated either with saline, or AO
      (alpha-tocopherol, l-ascorbic acid, zinc, and selenium), or therapeutic dose
      levels of etoposide (15 mg/kg) and cisplatin (3 mg/kg) from day 1-4 of the week
      and B (1.5 mg/kg) on the second day of the week, or BEP + AO. The real-time
      polymerase chain reaction showed that MTA1 and MTA1s (short form) gene expression
      was downregulated in AO (100% and 100%), BEP (86% and 71%), and BEP + AO (97% and
      93%) groups. Western blotting and immunohistochemistry results showed that
      unnormalized MTA1 protein expression was upregulated in AO (38%) and BEP + AO
      (34%) groups; however, the MTA1/beta-actin ratio was upregulated in all treated
      groups (21, 19, and 15%, respectively). In conclusion, the results indicate that
      both BEP and AO suppress MTA1 and MTA1s transcription, which may render the germ
      cells to be more prone to apoptosis. However, upregulation of MTA1 protein
      expression may be related to induced DNA damage. Modulation of MTA1 signaling is
      a novel mechanism of action of BEP and AO, which may be useful in developing
      newer anticancer drugs. 

PMID- 24021431
TI  - Dimethyl dimethoxy biphenyl dicarboxylate attenuates hepatic and metabolic
      alterations in high fructose-fed rats.
AB  - High fructose consumption is currently linked to metabolic disorders including
      insulin resistance and dyslipidemia as well as hepatic steatosis. Dimethyl
      dimethoxy biphenyl dicarboxylate (DDB) is a hepatoprotectant with antioxidant and
      anti-inflammatory properties. The aim of this study therefore is to evaluate the
      effect of DDB on high fructose-induced metabolic disturbances and hepatic
      steatosis in a rat model. Male Wistar rats were allocated into three groups:
      control, fructose-fed (10% in drinking water and 10% in diet), and fructose-fed
      DDB (300 mg/kg, orally)-treated groups. Rats were fed a high-fructose diet for 6
      weeks, while DDB was administered for an additional 2 weeks. High-fructose
      consumption elevated serum glucose and insulin levels and impaired oral glucose
      tolerance test, revealing insulin resistance. It also increased serum
      triglycerides and alanine aminotransferase as well as visceral fat content and
      decreased serum high-density lipoprotein. Additionally, histopathological
      examination revealed that high fructose intake induced hepatic steatosis. These
      alterations were associated with increased serum uric acid as well as hepatic
      content of malondialdehyde and nitric oxide (NO) in addition to overexpression of
      inducible NO synthase (iNOS). DDB administration significantly ameliorated the
      high fructose-induced hepatic and metabolic alterations. In conclusion, DDB
      ameliorates high fructose-induced metabolic disorders and hepatic steatosis in
      rats. Such protection is, at least in part, due to the inhibition of lipid
      peroxidation, decrease in iNOS overexpression, and reduction of elevated uric
      acid. 

PMID- 24021432
TI  - Chelation of thallium by combining deferasirox and desferrioxamine in rats.
AB  - The hypothesis that two known chelators deferasirox (4-[3,5-bis(2-hydroxyphenyl)
      1,2,4-triazol-1-yl]-benzoic acid) and desferrioxamine (DFO) might be more
      efficient as combined treatment than as monotherapies in removing thallium from
      the body was tested in a new acute rat model. 7-week-old male Wistar rats
      received chelators: deferasirox (orally), DFO (intraperitoneal; i.p.), or
      deferasirox + DFO as 75 or 150 mg/kg dose half an hour after a single i.p.
      administration of 8 mg thallium/kg body weight in the form of chloride. Serum
      thallium concentration, urinary thallium, and iron excretions were determined by
      graphite furnace atomic absorption spectrometry. Both chelators were effective
      only at the higher dose level, while DFO was more effective than deferasirox in
      enhancing urinary thallium excretion, deferasirox was more effective than DFO in
      enhancing urinary iron excretion. In the combined treatment group, deferasirox
      did not increase the DFO effect on thallium and DFO did not increase the effect
      of deferasirox on iron elimination. Our results support the usefulness of this
      animal model for preliminary in vivo testing of thallium chelators. Urinary
      values were more useful because of the high variability of serum results. 

PMID- 24021433
TI  - The effects of resveratrol against trifluralin toxicity in the urinary tract of
      rats.
AB  - The herbicide itself and the degradation products are highly toxic on biological
      systems. The aim of this study is to investigate the potential toxic effects of
      trifluralin (TRF) on the urinary system of male rats and to investigate the
      protective effects of resveratrol (RSV) in TRF-induced urinary system damage. A
      total of 35 male Wistar rats were randomly divided into: (1) control group, (2)
      sham group, (3) low dose TRF group (0.8 g/kg/day), (4) high dose TRF group (2
      g/kg/day) and (5) high dose TRF + RSV group 10 mg/kg/day. RSV was administered
      for 21 days by intragastric gavage at a dose of 10 mg/kg/day after induction of
      TRF. Kidney, ureter and urinary bladder tissue was examined using light
      microscopy and ultrastructurally. Terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labelling was performed to detect apoptosis. Superoxide dismutase
      (SOD), glutathion peroxidase (GPx) and malondialdehyde (MDA) levels were also
      evaluated biochemically for oxidative stress parameters. Histological evaluation
      showed that TRF increases apoptosis and oxidative stress, causes histological
      tissue damages and biochemical changes in the kidneys but does not cause any
      damage to the ureter and bladder. Treatment with RSV significantly attenuated
      tissue damage in the urinary system of rats. Apopitotic cells were significantly
      decreased in the treatment group. Additionally, treatment with RSV decreased SOD
      and GPx levels and increased MDA levels in the kidney tissue of animals subjected
      to TRF. These results show that RSV can significantly minimize histological
      damage and biochemical differences in treating TRF-induced kidney injury in rats.

PMID- 24021434
TI  - Free radical scavenging activity in in vitro-derived tissues of Eruca sativa.
AB  - Feasible regeneration protocol for economically important plant Eruca sativa was
      established and 1, 1-diphenyl-2-picrylhydrazyl scavenging activity of regenerated
      tissues was evaluated and compared with plant material collected from the wild.
      Leaf portions inoculated onto Murashige and Skoog (MS) medium responded to all
      plant growth regulators exploited. Optimum callus production was achieved on a
      combination of 2.0 mg l(-1) 6-benzyladenine (BA) + 1.0 mg l(-1) alpha-naphthalene
      acetic acid (NAA) and the lowest response was recorded for 0.5 mg l(-1)
      gibberellic acid (GA3) + 1.0 mg l(-1) NAA. The callus was subcultured on similar
      composition/concentrations of plant growth regulators after 4 weeks of culture
      time. A 5.0 mg l(-1) 6-BA + 1.0 mg l(-1) NAA produced optimum percentage shoot
      organogenesis after 4 weeks of subculturing. However, optimum number of shoots
      per explant was recorded for moderate concentrations (1.0 and 2.0 mg l(-1)) of
      kinetin. Incorporation of NAA into MS medium-containing GA3 also produced a
      feasible number of shoots/explant. Similar mean shoot length was recorded for 2.0
      mg l(-1) kinetin + 1.0 mg l(-1) NAA and optimum concentrations (2.0, 5.0, and
      10.0 mg l(-1)) of GA3 + 1.0 mg l(-1) NAA. In vitro generated shoots were shifted
      to MS medium augmented with indole acetic acid (IAA) for rooting after 4 weeks of
      subculturing. Moderate concentrations (5.0 mg l(-1)) of IAA produced feasible
      rooting. Investigation of radical scavenging activity showed that callus
      possesses higher levels of radical scavengers than other plant tissues tested.
      Phenolics and glucosides are reported to be active components of Eruca sativa
      phytochemistry.

PMID- 24021435
TI  - Evaluation of sugar content and composition in commonly consumed Korean
      vegetables, fruits, cereals, seed plants, and leaves by HPLC-ELSD.
AB  - In the present investigation, evaluation of sugars viz. fructose, galactose,
      glucose, sucrose, lactose, maltose, and raffinose in commonly consumed raw Korean
      vegetables, fruits, cereals, seed plants, and leaves has been analyzed using high
      performance liquid chromatography with evaporative light scattering detection
      (HPLC-ELSD). Of the 58 samples analyzed, Onion showed the highest content of
      fructose (27.74g/100g) and glucose (31.80g/100g) and Chestnuts showed the highest
      content of sucrose (21.82g/100g). On the other hand, Glutinous sorghum (polished
      grain), Green tea leaves, and Paddy rice (well-polished rice) showed the lowest
      content of fructose (0.20g/100g), glucose (0.68g/100g) and sucrose (0.23g/100g),
      respectively. Glutinous barley (Hopimbori-whole grain) and Green tea leaves
      showed 0.17g/100g and 0.57g/100g of galactose and lactose respectively. Glutinous
      barley (Seodunchalbori-polished grain) and Black soybeans (Cheongjaho, dried)
      showed the highest content of maltose (0.51g/100g) and raffinose (1.82g/100g),
      respectively. In few samples, galactose, maltose, lactose, and raffinose were
      detected in trace quantities. A partial least squares discriminant analysis (PLS
      DA) was also performed to discriminate the analyzed samples. 

PMID- 24021436
TI  - Reducing values: dinitrosalicylate gives over-oxidation and invalid results
      whereas copper bicinchoninate gives no over-oxidation and valid results.
AB  - A comparative study was made between two carbohydrate reducing value methods, a
      relatively old, highly alkaline, 3,5-dinitrosalicylic acid (DNSA) method and a
      relatively newer, low alkaline (pH 10.5), copper bicinchoninate (CuBic) method.
      Reducing values for a series of equimolar amounts of maltose-maltohexaose,
      isomaltose-isomaltohexaose, and cellobiose-cellohexaose were compared by the two
      methods. The DNSA method gave over-oxidation for equimolar amounts of all three
      of the oligosaccharide series. The amount of oxidation increased as the sizes of
      the oligosaccharides increased, giving inflated, inaccurate reducing values. The
      CuBic method gave constant reducing values, for equimolar amounts of the
      oligosaccharides, indicating that there was no over-oxidation, as the sizes of
      the oligosaccharides were increased. The two methods were used to determine the
      number average molecular weights (MWn) for six polysaccharides. The DNSA method
      was not able to determine the MWn for any of the polysaccharides tested due to
      the low sensitivity of the method, compared with the CuBic method that did not
      give over-oxidation and gave reasonable MWn values for all six of the
      polysaccharides tested. 

PMID- 24021437
TI  - Slip, slop, slap, seek, slide - is the message really getting across?
AB  - Australia has given a high priority to education programs emphasizing the
      relationship of sun exposure and skin cancer and teaching about sun safety and
      sun protection. Have these efforts been successful? 

PMID- 24021438
TI  - Taxane associated subacute cutaneous lupus erythematosus.
AB  - Numerous medications have been associated with the development of subacute
      cutaneous lupus erythematosus. A mechanism explaining how unrelated drug classes
      can lead to subacute cutaneous lupus erythematosus has remained elusive,
      suggesting that there may be multiple etiologic pathways. Taxanes (docetaxel,
      paclitaxel, and cabazitaxel) inhibit cell mitosis through microtubule
      stabilization and their use has uncommonly been associated with subacute
      cutaneous lupus erythematosus. Recently the antigen recognized by anti-Ro/SS-A
      antibody (Ro52) has been localized to the cytoplasmic microtubule network. A case
      report of docetaxel exacerbated subacute cutaneous lupus erythematosus is
      presented and literature review performed, revealing 11 additional cases of
      taxane associated subacute cutaneous lupus erythematosus. Taxanes are proposed to
      exacerbate or induce subacute cutaneous lupus erythematosus in immunogenetically
      predisposed patients by stabilizing microtubules and affecting Ro/SS-A antigen
      (Ro52) expression. This may be an under recognized adverse drug reaction because
      taxanes are used for a defined period and the cutaneous eruption tends to
      spontaneously improve. Studies analyzing how particular drug classes affect Ro/SS
      A antigen expression may be useful in identifying mechanisms of action in drug
      induced subacute cutaneous lupus erythematosus. 

PMID- 24021440
TI  - Clinical and histopathologic findings in cutaneous sting ray wounds: a case
      report.
AB  - Human injuries related to stingray attacks include deep puncture wounds,
      envenomation, and foreign body reactions owing to retained tail fragments. Herein
      we report a patient who sustained a stingray injury that produced a subcutaneous
      granulomatous dermatitis and panniculitis with necrobiosis and review the topic
      of stingray injuries. 

PMID- 24021439
TI  - Mycobacteria infection in an immunocompetent patient with no risk factors:
      evaluation and management of non-healing majocchi granuloma-type nodule.
AB  - Atypical mycobacterial infections are more commonly described among
      immunocompromised patients, although there has been an increasing incidence in
      recent years of infections in immunocompetent hosts. Normally preceding trauma is
      a risk factor for infection. We describe a case of Mycobacteria chelonae
      infection in a healthy individual with no risk factors. 

PMID- 24021441
TI  - Multiple myeloma diagnosed secondary to analysis of a lytic bone lesion
      encountered during Mohs micrographic surgery.
AB  - An 89-year-old man underwent Mohs micrographic surgery for treatment of a
      squamous cell carcinoma of the scalp. A lytic bone lesion was found that led to
      the diagnosis of multiple myeloma. 

PMID- 24021442
TI  - Unilateral purpura annularis telangiectodes of majocchi in an elderly male: an
      atypical presentation.
AB  - Purpura annularis telangiectodes (PAT), also known as Majocchi purpura, is a rare
      form of pigmented purpuric dermatosis characterized by non-palpable red-brown,
      occasionally pruritic patches which progress to hyperpigmented halos. Purpura
      annularis telangiectodes usually presents in female adolescents as benign
      symmetric lesions with a predilection for the lower extremities. We present an
      atypical case of unilateral PAT in an elderly male. To our knowledge, our patient
      at 85-years-old is the oldest PAT and first unilateral purpura annularis
      telangiectodes case described in the literature. 

PMID- 24021443
TI  - Trichofolliculoma: a rare variant of hair follicle hamartoma.
AB  - Trichofolliculoma is a rare hair follicle hamartoma, which is often regarded as a
      hair follicle tumor. Mostly, it presents as a papule or nodule, involving the
      skin of the face and scalp area. A central, dilated keratin plugged ostium with
      vellus hair(s) is often present. We report a 19-year-old woman with typical
      clinical and histopathological findings of trichofolliculoma. 

PMID- 24021444
TI  - Polymorphous low-grade adenocarcinoma in the upper lip: a well-described but
      infrequently recognized tumor.
AB  - Polymorphous low-grade adenocarcinoma (PLGA) is a rare malignant neoplasm arising
      almost exclusively in the minor salivary glands. PLGA occurs primarily in the
      oral cavity, especially in the palate, followed by the oral mucosa and upper lip
      [1,2]. Conditions involving these locations are often presented at dermatological
      clinics. Therefore, dermatologists should consider this entity in the
      differential diagnosis of the oral cavity tumors. We present a case of PLGA in
      the upper lip. 

PMID- 24021445
TI  - Two new cases with Costello syndrome.
AB  - Costello syndrome (CS) was described in 1977 by Costello who reported two
      unrelated children with a new syndrome comprising short stature, redundant skin
      of the neck, palms, soles, and fingers, curly hair, papillomata around the mouth
      and nares, and mental retardation. Several additional cases have been reported
      since then. Herein we report two patients with Costello syndrome; one of these
      patients had associated mesenteric cyst. 

PMID- 24021446
TI  - Hypopigmented micropapules in apparently quiescent morphea lesions: a
      manifestation of disease activity.
AB  - We present two young patients with morphea or localized scleroderma undergoing
      systemic treatment, who developed papular lesions on pre-existing sclerotic
      plaques. Histology was compatible with a papular presentation of morphea and
      other entities in the differential diagnosis were ruled out. We believe this is a
      very uncommon presentation of activity in lesions of morphea and should be made
      known to clinicians so that activity and progression of the disease can be
      recognized and treated to avoid complications. 

PMID- 24021447
TI  - Eccrine hidrocystomas presenting as multiple papules on the cheeks.
AB  - Hidrocystomas are common, benign adnexal neoplasms most frequently found on the
      eyelids, canthi, or periocular areas. Herein, we report a case of multiple
      hidrocystomas distributed over less common facial areas: cheeks and cutaneous
      lips. 

PMID- 24021448
TI  - Agminated syringocystadenoma papilliferum: a new clinical presentation of a rare
      benign adnexal neoplasm.
AB  - Syringocystadenoma papilliferum is a rare adnexal tumor that often occurs as a
      solitary tumor in the head and neck region, although occurrences on other
      anatomical locations have been described. Linear configurations have been
      described, but an agminated form is a more rare and underreported variant of this
      tumor. We describe a case of a healthy 10-year old female with agminated
      syringocystadenoma papilliferum occurring on her left supraclavicular region,
      with the clinical appearance of grouped molluscum contagiosum papules.Case
      synopsis A healthy 10-year-old girl was referred for the treatment of a
      "collection of molluscum contagiosum" of the left supra clavicular region of
      several years duration. The lesions were asymptomatic and refractory to
      cryotherapy. The patient was a healthy girl with no significant systemic
      findings. Cutaneous exam revealed a clustered group of pink, dome shaped,
      umbilicated papules over a 1.5 x 1 cm area within the left supraclavicular fossa
      (Figure 1a). An excisional biopsy was performed. Routine H&E stained sections
      revealed cystic epidermal invaginations with papillary projections. The
      superficial portions of the cyst were lined by stratified keratinizing
      epithelium, whereas the deeper papillated portion exhibited a double layer of
      basal-like cells and luminal eosinophilic columnar cells with focal decapitation
      secretion. The papillary structures contained fibrovascular cores and
      lymphoplasmacytic infiltrates. A component of hamartomatous follicular growth was
      not identified (Figure 1b-d.). A diagnosis was made of agminated
      syringocystadenoma papilliferum. 

PMID- 24021449
TI  - PHACES syndrome with moyamoya vasculopathy - a case report.
AB  - "PHACES" (OMIM 606519) is a neurocutaneous disorder, and facial hemangiomas are
      the hallmark of this syndrome. The syndrome encompasses posterior fossa brain
      malformations, facial hemangiomas, arterial anomalies, aortic coarctation,
      cardiac anomalies, eye abnormalities, and sternal defects. 

PMID- 24021450
TI  - A 29-year-old man with exophytic Kaposi sarcoma and edema of the bilateral legs
      in the setting of immune reconstitution inflammatory syndrome.
AB  - A 29-year-old man with a history of HIV, previously noncompliant with
      antiretroviral therapy, restarted highly active antiretroviral therapy (HAART) 4
      weeks prior to the sudden development of multiple tender exophytic friable tumors
      and subcutaneous nodules of the thighs. Herein we present a patient with Kaposi
      sarcoma in the setting of immune reconstitution inflammatory syndrome. 

PMID- 24021451
TI  - Pityrosporum folliculitis in an immunocompetent patient: clinical case
      description.
AB  - The present report concerns Malassezia-related pityrosporum folliculitis in a
      patient without any predisposing factor. Once the diagnosis had been confirmed by
      histopathologic exam, the patient was treated with oral ketoconazole and selenium
      sulfide shampoo; complete remission of the clinical condition was obtained. Thus
      it could be concluded that in spite of being routinely associated with
      immunosuppression, this condition may be present in an immunocompetent patient. 

PMID- 24021452
TI  - Congenital drainage at the base of the neck.
AB  - Heterotopic salivary gland tissue consists of otherwise normal salivary tissue,
      but occurs at a site in which it is normally not present (outside of the major,
      minor, and accessory salivary glands), with absence of clinical and histological
      features of branchial cleft anomalies. We herein present a 7-year-old boy with
      drainage from a small, congenital cystic lesion located at the base of the neck,
      which was histologically confirmed as salivary gland tissue. 

PMID- 24021453
TI  - Reversible cerebral vasoconstriction syndrome identification of prognostic
      factors.
AB  - OBJECT: Reversible cerebral vasoconstriction syndrome (RCVS) is described as a
      clinical and radiological entity characterized by thunderclap headaches, a
      reversible segmental or multifocal vasoconstriction of cerebral arteries with or
      without focal neurological deficits or seizures. The purpose of this study is to
      determine risk factors of poor outcome in patients presented a RCVS. METHODS: A
      retrospective multi-center review of invasive and non-invasive neurovascular
      imaging between January 2006 and January 2011 has identified 10 patients with
      criterion of reversible segmental vasoconstriction syndrome. Demographics data,
      vascular risks and evolution of each of these patients were analyzed. RESULTS:
      Seven of the ten patients were females with a mean age of 46 years. In four
      patients, we did not found any causative factors. Two cases presented RCVS in
      post-partum period between their first and their third week after delivery. The
      other three cases were drug-induced RCVS, mainly vaso-active drugs. Cannabis was
      found as the causative factor in two patient, Sumatriptan identified in one
      patient while cyclosporine was the causative agent in also one patient. The mean
      duration of clinical follow-up was 10.2 months (range: 0-28 months). Two patients
      had neurological sequelae: one patient kept a dysphasia and the other had a
      homonymous lateral hemianopia. We could not find any significant difference of
      the evolution between secondary RCVS and idiopathic RCVS. The only two factors,
      which could be correlated to the clinical outcome were the neurological status at
      admission and the presence of intraparenchymal abnormalities (ischemic stroke,
      hematoma) in brain imaging. CONCLUSIONS: Fulminant vasoconstriction resulting in
      progressive symptoms or death has been reported in exceptional frequency.
      Physicians had to remember that such evolution could happen and predict them by
      identifying all factors of poor prognosis (neurological status at admission, the
      presence of intraparenchymal abnormalities).

PMID- 24021454
TI  - Development of a movement and state plan for obesity prevention, Eat Smart, Move
      More North Carolina.
AB  - This report outlines the evolution of the Eat Smart, Move More North Carolina
      movement and publications in support of the movement, including North Carolina's
      Plan to Address Obesity: Healthy Weight and Healthy Communities, 2013-2020. This
      evidence-based plan guides the efforts of many organizations as they work to
      fulfill the mission of Eat Smart, Move More North Carolina: to reverse the rising
      tide of obesity and chronic disease among North Carolinians by helping them to
      eat smart, move more, and achieve a healthy weight. 

PMID- 24021455
TI  - Knowledge and practices of using food label information among adolescents
      attending schools in Kolkata, India.
AB  - OBJECTIVE: To assess knowledge and use of label information among adolescents.
      METHODS: A cross-sectional study was conducted among adolescents (N = 316) from 6
      schools selected randomly using cluster sampling. A pre-coded questionnaire was
      used to assess frequently consumed packaged foods, whether label information was
      read, knowledge of symbols, and usefulness of nutrition information display. The
      data were analyzed using descriptive statistics and chi-square tests. RESULTS:
      Although 88% of adolescents read food labels, many read only date of manufacture
      (79%), expiration (74%) or best used before dates (65%). Fewer adolescents read
      ingredients (50%) and nutrition information (20%). Their knowledge about quality
      symbols was low. Many of them (over 60%) recognized the symbols but had no
      knowledge of what they indicated. About 66% believed that nutrition information
      on labels was too complex to understand. CONCLUSIONS AND IMPLICATIONS: There is a
      need to provide education on different aspects of label information to promote
      label use. The effectiveness of alternative methods of nutrition information
      display should also be investigated.

PMID- 24021456
TI  - Food insecurity is linked to a food environment promoting obesity in households
      with children.
AB  - OBJECTIVE: To determine the extent to which the presence and accessibility of
      healthful and less healthful foods in children's homes vary with level of food
      security. METHODS: A total of 41 parents or primary caregivers who had at least 1
      child ages 2-13 and resided in a low-income area with limited food access
      completed a home food inventory and a validated measure assessing household food
      security. RESULTS: Compared with food-secure participants, marginal or low/very
      low food-secure caregivers reported significantly more obesity-promoting foods in
      the home, more microwavable or quick-cook frozen foods, and greater access to
      less healthful foods in the kitchen (all Ps < .05). CONCLUSIONS AND IMPLICATIONS:
      Given the greater presence and accessibility of less healthful foods, targeting
      home food environment may improve diet quality and health status in children of
      low-income, food insecure households.

PMID- 24021457
TI  - Understanding African American women's decisions to buy and eat dark green leafy
      vegetables: an application of the reasoned action approach.
AB  - OBJECTIVE: Examine intentions to buy and eat dark green leafy vegetables (DGLV).
      DESIGN: Cross-sectional survey assessing demographics, behavior, intention, and
      Reasoned Action Approach constructs (attitude, perceived norm, self-efficacy).
      SETTING: Marion County, Indiana. PARTICIPANTS: African American women responsible
      for buying and preparing household food. MAIN OUTCOME MEASURE(S): Reasoned Action
      Approach constructs explaining intentions to buy and eat DGLV. ANALYSIS: Summary
      statistics, Pearson correlations, and multiple regression analyses. RESULTS:
      Among participants (n = 410, mean age = 43 y), 76% and 80%, respectively,
      reported buying and eating DGLV in the past week. Mean consumption was 1.5 cups
      in the past 3 days. Intentions to buy (r = 0.20, P < .001) and eat (r = 0.23, P <
      .001) DGLV were positively associated with consumption. Reasoned Action Approach
      constructs explained 71.2% of the variance in intention to buy, and 60.9% of the
      variance in intention to eat DGLV. Attitude (beta = .63) and self-efficacy (beta
      = .24) related to buying and attitude (beta = .60) and self-efficacy (beta = .23)
      related to eating DGLV explained significant amounts of variance in intentions to
      buy and eat more DGLV. Perceived norm was unrelated to either intention to buy or
      eat DGLV. CONCLUSIONS AND IMPLICATIONS: Interventions designed for this
      population of women should aim to improve DGLV-related attitudes and self
      efficacy.

PMID- 24021458
TI  - Bivalent vaccination against pneumonic pasteurellosis in domestic sheep and goats
      with modified-live in-frame lktA deletion mutants of Mannheimia haemolytica.
AB  - A temperature-sensitive shuttle vector, pBB80C, was utilized to generate in-frame
      deletion mutants of the leukotoxin structural gene (lktA) of Mannheimia
      haemolytica serotypes 1, 2, 5, 6, 7, 8, 9, and 12. Culture supernatants from the
      mutants contained a truncated protein with an approximate molecular weight of 66
      kDa which was reactive to anti-leukotoxin monoclonal antibody. No protein
      reactive to anti-LktA monoclonal antibody was detected at the molecular weight
      100-105 kDa of native LktA. Sheep and goats vaccinated intramuscularly with a
      mixture of serotypes 5 and 6 mutants were resistant to virulent challenge with a
      mixture of the wild-type parent strains. These vaccinates responded serologically
      to both vaccine serotypes and exhibited markedly-reduced lung lesion volume and
      pulmonary infectious load compared to control animals. Control animals yielded a
      mixture of serotypes from lung lobes, but the proportion even within an
      individual animal varied widely from 95% serotype 5-95% serotype 6. Cultures
      recovered from liver were homogeneous, but two animals yielded serotype 5 and the
      other two yielded serotype 6 in pure culture. 

PMID- 24021459
TI  - Angiographically documented transient monocular blindness: retinal migraine?

PMID- 24021460
TI  - Do psychosis patients with poor insight show implicit awareness on the emotional
      stroop task?
AB  - BACKGROUND: The insight into psychosis can be assessed reliably by clinicians
      from interviews with patients. However, patients may retain implicit awareness of
      illness while lacking explicit awareness. SAMPLING AND METHODS: In a sample of
      first-episode psychosis patients, we used a test of processing of mental illness
      related and other negative words as a measure of implicit awareness to see how
      this varied in relation to insight. An emotional-counting Stroop task tested
      reaction times to words of three types: psychosis-related (e.g. 'crazy'), general
      negative (e.g. 'cancer') and neutral (e.g. 'oyster'). Data were available from 43
      patients and 23 healthy controls. Patients' insight was assessed using the
      Schedule for the Assessment of Insight (SAI-E). RESULTS: Patients reacted slower
      than controls to words across all conditions, and both patients and controls
      reacted slower to salient and negative words than neutral words. There was a near
      significant interaction between word type and group (Wilks' lambda = 0.53, p =
      0.055); patients experienced greater interference from negative rather than
      psychosis-related words (p = 0.003), and controls experienced greater
      interference from salient rather than negative words (p = 0.01). Within the
      patient group, there was a correlation between insight and interference on
      salient words (r = 0.33, p = 0.05), such that those with less insight experienced
      less interference on psychosis-related words. CONCLUSIONS: Psychosis-related
      words were less threatening and less self-relevant to psychosis patients with
      less insight. This suggests that the lack of awareness such patients have of
      their illness is genuine and more likely to be mediated by lower-level
      information processing mechanisms than strategies such as conscious, motivated
      denial.

PMID- 24021461
TI  - Synthesis of the non-peptidic snail toxin 6-bromo-2-mercaptotryptamine dimer
      (BrMT)(2), its lower and higher thio homologs and their ability to modulate
      potassium ion channels.
AB  - The first synthesis of the non-peptidic snail toxin 6-bromo-2-mercaptotryptamine
      dimer (BrMT)2 is described, along with the preparation of its lower and higher
      thio homologs. The synthetic (BrMT)2 and its derivatives reported herein are all
      capable of slowing the activation of the Kv1.1 potassium ion channel. Only the
      monosulfide variant shows significant slowing of the deactivation process. This
      synthetic strategy can now be applied to creating a more extensive set of
      compounds that vary in the length of the linker connecting the two monomers, the
      substituents on the indole ring core, and terminal amine. 

PMID- 24021462
TI  - Heteroannelated and 7-deoxygenated goniofufurone mimics with antitumour activity:
      design, synthesis and preliminary SAR studies.
AB  - Cytotoxic (+)-goniofufurone mimic such as benzoxepane 2 was preferentially formed
      after the treatment of 7-O-benzoyl-5-O-benzyl (+)-goniofufurone derivative 6 with
      titanium(IV) fluoride. However, the corresponding 7-epimer 5 (derivative of 7-epi
      goniofufurone) under the similar reaction conditions gave mainly 7-deoxy
      derivative 7 as a result of an unexpected 1,5-hydride shift. Extension of this
      methodology to the enantiomer ent-6 provided cytotoxic (-)-goniofufurone mimics
      ent-2 and ent-7. Synthesized compounds showed diverse growth inhibitory effects
      against selected tumour cell lines, but were devoid of any significant toxicity
      towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the
      structural features of these lactones that are beneficial for their
      antiproliferative activity, such as presence of an additional oxepane ring, the
      absolute stereochemistry and the presence of a deoxy function at the C-7
      position. 

PMID- 24021464
TI  - Global climate change and despair: a way out.

PMID- 24021463
TI  - Identification of amides derived from 1H-pyrazolo[3,4-b]pyridine-5-carboxylic
      acid as potent inhibitors of human nicotinamide phosphoribosyltransferase
      (NAMPT).
AB  - Potent, 1H-pyrazolo[3,4-b]pyridine-containing inhibitors of the human
      nicotinamide phosphoribosyltransferase (NAMPT) enzyme were identified using
      structure-based design techniques. Many of these compounds exhibited nanomolar
      antiproliferation activities against human tumor lines in in vitro cell culture
      experiments, and a representative example (compound 26) demonstrated encouraging
      in vivo efficacy in a mouse xenograft tumor model derived from the A2780 cell
      line. This molecule also exhibited reduced rat retinal exposures relative to a
      previously studied imidazo-pyridine-containing NAMPT inhibitor. Somewhat
      surprisingly, compound 26 was only weakly active in vitro against mouse and
      monkey tumor cell lines even though it was a potent inhibitor of NAMPT enzymes
      derived from these species. The compound also exhibited only minimal effects on
      in vivo NAD levels in mice, and these changes were considerably less profound
      than those produced by an imidazo-pyridine-containing NAMPT inhibitor. The
      crystal structures of compound 26 and the corresponding PRPP-derived ribose
      adduct in complex with NAMPT were also obtained. 

PMID- 24021465
TI  - A perspective on health professions education.

PMID- 24021466
TI  - Gun deaths, the invisible epidemic, by the numbers.

PMID- 24021467
TI  - The International Congress for Educators in Complementary and Integrative
      Medicine.

PMID- 24021468
TI  - Research training in integrative medicine: how can we make teaching and learning
      in research methods more sustainable and engaging?
AB  - BACKGROUND: The aim of this project was to identify strategies for increasing
      learner engagement and knowledge retention in clinical research training of
      complementary and integrative medicine (CIM) practitioners, and to offer a
      conceptual framework to address clinical research training for CIM practitioners.
      METHODS: In a featured large-group discussion (15min presentation and 30min
      discussion), two questions (strategies that are recommended to overcome these
      barriers; relevant aspects for a framework for building sustainable knowledge)
      were put to the audience. The sample consisted of 43 participants at the
      International Congress of Educators in Complementary and Alternative Medicine, in
      Washington, DC, in October 2012. The featured discussion was moderated and
      detailed notes were taken. Notes were synthesized and discussed by both authors
      until consensus was reached. Based on the results from the featured discussion
      session and a focused literature search, a framework for building sustainable
      knowledge and skills in clinical research for CIM practitioners was developed.
      RESULTS: Participants' responses to the questions of engagement and
      sustainability included curricular structures, pedagogical strategies for
      instruction, the use of digital tools to extend the learning experience, the
      necessity to ground instruction firmly in the medical literature of the field,
      and the relevance of mentoring. Key considerations for building sustainable
      knowledge in clinical research for CIM practitioners are as follows: (1)
      prioritizing clinical research training, (2) issues of curriculum and pedagogy,
      (3) technology/digital tools, (4) administrative challenges, (5) supporting the
      formation of communities of practice, and (6) cultural perspectives of CIM
      practitioners.

PMID- 24021469
TI  - Competencies for optimal practice in integrated environments: examining
      attributes of a consensus interprofessional practice document from the licensed
      integrative health disciplines.
AB  - INTRODUCTION: The Academic Consortium for Complementary and Alternative Health
      Care (ACCAHC) is committed to advancing human health through the advancement and
      integration of the complementary and alternative medicine (CAM) professions
      within the American healthcare system. This will involve the maturation and
      integration of the licensed CAM professions into conventional healthcare
      delivery, and in turn, it will involve the development of competency in
      integrative healthcare and interprofessional education within the CAM
      professions. METHOD AND RESULTS: In 2010, ACCAHC resolved to identify the
      competencies necessary for this transformation, and in the process, discovered a
      parallel process of competency development within conventional healthcare, the
      Interprofessional Education Collaborative (IPEC), representing the six major
      conventional healthcare professions. DISCUSSION: The ACCAHC competency document,
      its development, and its similarity to the IPEC document are discussed. The
      ACCAHC competency document identified two domains of competence that were not
      present in the IPEC document: evidence-informed practice and institutional
      healthcare practices. These two domains of competency are discussed with respect
      to their significance in both CAM and conventional healthcare practices.
      CONCLUSION: ACCAHC's goal is to foster collaboration among its member professions
      and with conventional healthcare professions, and to use these competency
      documents to improve and optimize healthcare delivery, practices, and outcomes in
      America. It is hoped that ACCAHC's competency document will catalyze interaction
      with IPEC leading to the adoption of a single shared competency document that
      will meet the needs of all healthcare providers and educators.

PMID- 24021470
TI  - A medical student elective promoting humanism, communication skills,
      complementary and alternative medicine and physician self-care: an evaluation of
      the HEART program.
AB  - OBJECTIVE: In 2002 the American Medical Student Association (AMSA) created a
      fourth-year medical student elective known as the Humanistic Elective in
      alternative medicine, Activism, and Reflective Transformation (HEART) that
      provided the opportunity for students to explore humanism in medicine, self-care,
      complementary and alternative medicine modalities, communication, activism, and
      community building in a four-week immersion experience. The educational effects
      of this elective, and whether it has met its stated goals, are unknown. METHOD:
      The authors conducted a web-based, cross-sectional survey of the first eight
      cohorts of HEART graduates in 2010. Survey questions assessed respondents'
      demographics and perspectives on the educational impact of the elective.
      Descriptive statistics were used to characterize the sample and qualitative
      analyses were guided by grounded theory. RESULTS: Of 168 eligible alumni, 122
      (73%) completed the survey. The majority were female (70%), age <=35 (77%) years,
      and trained in primary care specialties (66%). Half were attendings in practice.
      The majority of respondents felt the elective taught professionalism (89%) and
      communication skills (92%) well or very well. The majority highly agreed that the
      elective helped them better cope with stress during residency training (80%),
      taught them self-care skills (75%), and improved their ability to empathize and
      connect with patients (71%). Qualitative analysis of the personal and
      professional impact of the elective identified twelve common themes with self
      discovery, self-care, and collegial development/community most frequently cited.
      CONCLUSIONS: The majority of HEART graduates endorse learning important skills
      and benefiting from the experience both personally and professionally. Aspects of
      the HEART curriculum may help training programs teach professionalism and improve
      trainee well-being.

PMID- 24021471
TI  - Family medicine residency program directors attitudes and knowledge of family
      medicine CAM competencies.
AB  - CONTEXT: Little is known about the incorporation of integrative medicine (IM) and
      complementary and alternative medicine (CAM) into family medicine residency
      programs. OBJECTIVE: The Society for Teachers of Family Medicine (STFM) approved
      a set of CAM/IM competencies for family medicine residencies. We hope to evaluate
      whether residency programs are implementing such competencies into their
      curriculum using an online survey tool. We also hope to assess the knowledge and
      attitudes of Residency Directors (RDs) on the CAM/IM competencies. DESIGN: A
      survey was distributed by the Council of Academic Family Medicine (CAFM)
      Educational Research Alliance to RDs via e-mail. The survey was distributed to
      431 RDs. Of those who received it, 212 responded, giving a response rate of
      49.1%. Questions assessed the knowledge and attitudes of CAM/IM competencies and
      incorporation of CAM/IM into the residency curriculum. RESULTS: Forty-five
      percent of RDs were aware of the competencies. In terms of RD attitudes, 58%
      reported that CAM/IM is an important component of residents' curriculum; yet, 60%
      report not having specific learning objectives for CAM/IM in their residency
      curriculum. Among all programs, barriers to CAM/IM implementation included time
      in residents' schedules (77%); faculty training (75%); access to CAM experts
      (43%); lack of reimbursement (43%); and financial resources (29%). CONCLUSIONS:
      While many RDs are aware of the STFM CAM/IM competencies and acknowledge their
      role in residence education, there are many barriers that prevent residencies
      from implementing the STFM CAM/IM competencies.

PMID- 24021472
TI  - Recommended integrative medicine competencies for family medicine residents.
AB  - BACKGROUND: The use of complementary and alternative medicine (CAM) and
      Integrative Medicine (IM) has grown steadily over the past decade. Patients seek
      physician guidance, yet physicians typically have limited knowledge and training.
      There is some coverage of IM/CAM topics in medical schools and residencies but
      with little coordination or consistency. METHODOLOGY: In 2008, the Society of
      Teachers of Family Medicine (STFM) group on Integrative Medicine began the
      process of designing a set of competencies to educate Family Medicine residents
      in core concepts of IM. The goal was creation of a set of nationally recognized
      competencies tied to the Accreditation Council for Graduate Medical Education
      (ACGME) domains. These competencies were to be achievable by diverse programs,
      including those without significant internal resources. The group compiled
      existing curricula from programs around the country and distilled these
      competencies through multiple reviews and discussions. Simultaneously, the
      Integrative Medicine in Residency program run by the University of Arizona
      underwent a similar process. In 2009, these competencies were combined and
      further developed at the STFM annual meeting by a group of experts. RESULTS: In
      2010, the STFM Board approved 19 measurable competencies, each categorized by
      ACGME domain, as recommended for Family Medicine residencies. Programs have
      implemented these competencies in various ways given individual needs and
      resources. CONCLUSIONS: This paper reviews the development of IM competencies for
      residency education in Family Medicine and presents those endorsed by STFM. By
      educating physicians in training about IM/CAM via competency-based curricula, we
      aim to promote comprehensive patient-centered care.

PMID- 24021473
TI  - Competencies for public health and interprofessional education in accreditation
      standards of complementary and alternative medicine disciplines.
AB  - This review examines the educational accreditation standards of four licensed
      complementary and alternative medicine (CAM) disciplines (naturopathic medicine,
      chiropractic health care, acupuncture and oriental medicine, and massage
      therapy), and identifies public health and other competencies found in those
      standards that contribute to cooperation and collaboration among the health care
      professions. These competencies may form a foundation for interprofessional
      education. The agencies that accredit the educational programs for each of these
      disciplines are individually recognized by the United States Department
      (Secretary) of Education. Patients and the public are served when healthcare
      practitioners collaborate and cooperate. This is facilitated when those
      practitioners possess competencies that provide them the knowledge and skills to
      work with practitioners from other fields and disciplines. Educational
      accreditation standards provide a framework for the delivery of these
      competencies. Requiring these competencies through accreditation standards
      ensures that practitioners are trained to optimally function in integrative
      clinical care settings. 

PMID- 24021474
TI  - Capsaicin for postherpetic neuralgia, antenatal self-hypnosis training, Tai chi
      to reduce fall risk, acupuncture for acute low back pain, and biofeedback for
      tension headache.

PMID- 24021475
TI  - Can the tall cell variant of papillary thyroid carcinoma be distinguished from
      the conventional type in fine needle aspirates? A cytomorphologic study with
      assessment of diagnostic accuracy.
AB  - OBJECTIVES: The tall cell variant of papillary thyroid carcinoma (TCV-PTC) is an
      aggressive variant of PTC requiring accurate cytopathologic diagnosis for early
      aggressive management. STUDY DESIGN: Twenty-five cases of TCV-PTC in which the
      tall cells comprised at least 30% of surgically resected tumor were included in
      the study. The direct smears from a preoperative fine needle aspiration (FNA) and
      available hematoxylin and eosin cell block sections were reviewed. Ten cases of
      TCV-PTC were randomly selected and blinded with an equal number of conventional
      PTC cases. Representative slides were independently reviewed by 7 cytologists.
      RESULTS: In a majority of the cases, the FNA direct smears were hypercellular and
      displayed flat monolayer sheets of cells. Tall columnar cells with cytoplasmic
      tails were seen in 56% of cases. The presence of large polygonal follicular cells
      with abundant granular oncocytic cytoplasm and distinct cell borders was the most
      common feature seen in all cases. Seventeen (68%) cases displayed intranuclear
      pseudoinclusions in cells with abundant granular cytoplasm. A correct diagnosis
      of TCV-PTC was made in 30-40% of cases by 7 study participants. CONCLUSIONS: The
      correct recognition of TCV-PTC features in preoperative FNA is important for
      clinical management, and reporting these features in a cytopathology report is
      suggested.

PMID- 24021476
TI  - Acute management of ST-elevation myocardial infarction patients taking
      dabigatran.
AB  - The novel oral anticoagulant agents provide compelling evidence-based advance
      over warfarin therapy in nonvalvular atrial fibrillation and have received
      endorsement from contemporary guidelines. This case illustrates the challenge
      that clinicians will have to manage patients taking these agents who present with
      ST-elevation myocardial infarction requiring acute reperfusion therapy. We used a
      "logical" although not evidence-based approach to applying a pharmacoinvasive
      strategy that might be considered by others. Additionally we propose suggestions
      for urgent percutaneous coronary intervention while taking dabigatran, a strategy
      that should be implemented cautiously and adapted as further evidence becomes
      available. 

PMID- 24021478
TI  - Evaluation of two screening methods for undiagnosed diabetes in China: an cost
      effectiveness study.
AB  - AIMS: To evaluate the performance and cost-effectiveness of two screening methods
      to identify undiagnosed diabetes at primary care settings among a Chinese
      population. METHODS: Two screening methods using a fasting capillary glucose
      (FCG) test or a Chinese diabetes risk score (DRS) at primary care settings
      followed by diagnostic tests were compared. The performance of FCG and DRS was
      evaluated by using receiver operating characteristic (ROC) curve analysis. The
      main economic outcome measures were the total cost of screening per 1000 persons,
      proportion of undiagnosed diabetes detected, and cost per undiagnosed diabetes
      identified from the societal perspective. RESULTS: Among all participants, 14.6%
      (1349/9232) had undiagnosed diabetes defined by fasting plasma glucose >=
      7.0mmol/l and/or 2h plasma glucose >= 11.1mmol/l and/or hemoglobin A1c >= 6.5%.
      At the optimal cutoff point of 6.1mmol/l for FCG and 14 for DRS, the sensitivity
      was 65.1% and 65.8%, and specificity was 72.4% and 55.2%, respectively. The area
      under the ROC curve was 75.3% for FCG and 63.7% for DRS (P<0.001). Based on the
      input costs, the total cost of screening 1000 persons was Y64,000 ($9143) for FCG
      and Y81,000 ($11,571) for DRS. The average cost per case identified was Y674
      ($96) for FCG at cutoff point of 6.1mmol/l and Y844 ($121) for DRS at score of
      14. The incremental cost per case identified was Y17,000 ($2429) for DRS compared
      to FCG. The dominance relations between strategies remained with the changed in
      sensitivity analysis. CONCLUSIONS: As a first-line screening tool for undiagnosed
      diabetes, the FCG test performed better than the DRS in primary care settings in
      China. The non-invasive and layperson-oriented DRS was feasible and detected more
      cases but more expensive. No strategy has strong dominance that was both more
      effective and less costly. The favorable strategy will depend on if the purpose
      of the screening program is to identify more cases or to have lower cost per
      case.

PMID- 24021477
TI  - Loss of caveolin-1 expression in knock-in mouse model of Huntington's disease
      suppresses pathophysiology in vivo.
AB  - Loss of cholesterol homeostasis and altered vesicle trafficking have been
      detected in Huntington's disease (HD) cellular and animal models, yet the role of
      these dysfunctions in pathophysiology of HD is unknown. We demonstrate here that
      defects in caveolar-related cholesterol trafficking directly contribute to the
      mechanism of HD in vivo. We generated new mouse models that express mutant
      Huntington's protein (mhtt), but have partial or total loss of caveolin-1 (Cav1)
      expression. Fluorescence resonance energy transfer dequenching confirms a direct
      interaction between mhtt and Cav1. Mhtt-expressing neurons exhibited cholesterol
      accumulation and suppressed caveolar-related post-Golgi trafficking from
      endoplasmic reticulum/Golgi to plasma membrane. Loss or reduction of Cav1
      expression in a knock-in HD mouse model rescues the cholesterol phenotype in
      neurons and significantly delays the onset of motor decline and development of
      neuronal inclusions. We propose that aberrant interaction between Cav1 and mhtt
      leads to altered cholesterol homeostasis and plays a direct causative role in the
      onset of HD pathophysiology in vivo. 

PMID- 24021479
TI  - Identifying people with type 2 diabetes and those at risk: lessons from the
      measure your waist (MY-WAIST) mixed-methods study in UK primary care.
AB  - AIMS: This paper focuses mainly on explanations and lessons from a research-based
      programme for identifying undiagnosed type 2 diabetes and high risk. In addition
      to outlining key quantitative findings, we specifically aim to explore reasons
      for low uptake from the perspective of primary care staff involved. METHODS: The
      MY-WAIST study was conducted in UK primary care and included the use of oral
      glucose tolerance tests (OGTTs) and waist measurement. Qualitative data from
      interviews with healthcare providers and records of meetings were analysed
      thematically. RESULTS: The key quantitative finding was low uptake of the
      assessments offered (8.6% overall, 2.6% in inner-city locations with high South
      Asian residency). In addition to confirming patient-reported barriers including
      those associated with OGTTs, qualitative findings highlighted a number of primary
      care provider barriers, including limited staff capacity. Interviewees suggested
      that those who attended were typically the 'worried well' rather than those from
      hard-to-reach groups. CONCLUSIONS: Implications discussed include the impact of
      low uptake on the usefulness of the quantitative data obtained, and lessons
      relevant to research design. Relevance to current guidance regarding early
      identification strategies is discussed and the importance of addressing the needs
      of less accessible groups is highlighted.

PMID- 24021480
TI  - Effects of isolated GH deficiency on adipose tissue, feeding and adipokines in
      mice.
AB  - OBJECTIVE: Growth hormone deficiency (GHD) leads to growth failure and changes in
      body composition including increased fat accumulation and reduced lean body mass
      in both humans and rodents. The aim of this study was to characterize the
      consequences of isolated GHD (IGHD) on adiposity, total body weight (TBW), and
      food intake in a mouse model of autosomal recessive IGHD due to targeted ablation
      of the GH-releasing hormone (GHRH) gene [GHRH knockout (GHRHKO)]. Animals were
      also analyzed with respect to leptin, adiponectin and visfatin circulating levels
      and gene expression in both intra-abdominal and subcutaneous fat. DESIGN: We
      studied 8 male mice homozygous for GHRHKO allele (-/-) and 8 heterozygous (+/-)
      animals as controls. Feeding and TBW data were collected weekly from 3 through 5
      months of age. Animals were then euthanized for measurement of body length and
      intra-abdominal (epididymal and retroperitoneal) and subcutaneous (interscapular,
      axillary, gluteal and inguinal) fat weights, and for blood collection for leptin,
      adiponectin and visfatin measurement. Gene expression of leptin, adiponectin and
      visfatin in adipose tissue was evaluated by real-time reverse transcription
      polymerase chain reaction. RESULTS: GHRHKO mice had significantly increased
      relative intra-abdominal (P<0.01) and subcutaneous (P<0.0001) fat, accompanied by
      significantly increased food intake per TBW (P<0.01), whereas - despite 40%
      higher food consumption--TBW change was not different from controls over the 2
      month period. Adiponectin and visfatin mRNA levels were decreased in both intra
      abdominal (P<0.001) and subcutaneous fat (P<0.0001), while leptin mRNA levels
      were not different from controls. Conversely, serum adiponectin levels were
      higher in GHRHKO mice (P<0.0001), whereas serum visfatin and leptin did not
      significantly differ from controls. CONCLUSIONS: IGHD due to targeted ablation of
      the GHRH gene in mice is associated with increased relative subcutaneous and
      intra-abdominal fat mass and higher food consumption which is not related to
      changes in circulating leptin.

PMID- 24021481
TI  - A comparison of ecological optima of soft-bodied benthic algae in Norwegian and
      Austrian rivers and consequences for river monitoring in Europe.
AB  - Alpine and Nordic rivers are often considered as being among the most pristine in
      Europe. Nevertheless, acidification and eutrophication impact surface waters in
      these regions. Soft-bodied, i.e. non-diatom, benthic algae are used as indicators
      for eutrophication and acidification in both Norway and Austria, but consistency
      of indicator values has never been tested. We compared species optima with
      respect to pH, conductivity, total phosphorus (TP), and NO3(-)-N concentration
      for 21 species, derived from geographically and temporally extensive datasets
      from Norway and Austria, respectively. The ranges of all four measured parameters
      were different between Norway and Austria, with Austria having generally higher
      values for all measured parameters. Optima for all 21 species with respect to pH,
      conductivity and NO3(-)-N were significantly different between Norway and
      Austria, while 5 of the 21 taxa showed no significant differences for TP.
      Nevertheless, species optima for Norway and Austria were significantly correlated
      with each other for TP, pH and conductivity. This indicates that positions of
      species optima relative to each other may be stable across ecoregions, in spite
      of the absolute values of species optima being different. In contrast, optima
      with respect to NO3(-)-N were not correlated, possibly suggesting a lesser
      importance of NO3(-) in shaping benthic algal assemblages than TP and pH. We
      conclude that the use of eutrophication and acidification models across different
      ecoregions may give meaningful results, but requires regional testing of species
      optima.

PMID- 24021482
TI  - Planar cell polarity proteins differentially regulate extracellular matrix
      organization and assembly during zebrafish gastrulation.
AB  - Zebrafish gastrulation cell movements occur in the context of dynamic changes in
      extracellular matrix (ECM) organization and require the concerted action of
      planar cell polarity (PCP) proteins that regulate cell elongation and
      mediolateral alignment. Data obtained using Xenopus laevis gastrulae have shown
      that integrin-fibronectin interactions underlie the formation of polarized cell
      protrusions necessary for PCP and have implicated PCP proteins themselves as
      regulators of ECM. By contrast, the relationship between establishment of PCP and
      ECM assembly/remodeling during zebrafish gastrulation is unclear. We previously
      showed that zebrafish embryos carrying a null mutation in the four-pass
      transmembrane PCP protein vang-like 2 (vangl2) exhibit increased matrix
      metalloproteinase activity and decreased immunolabeling of fibronectin. These
      data implicated for the first time a core PCP protein in the regulation of
      pericellular proteolysis of ECM substrates and raised the question of whether
      other zebrafish PCP proteins also impact ECM organization. In Drosophila
      melanogaster, the cytoplasmic PCP protein Prickle binds Van Gogh and regulates
      its function. Here we report that similar to vangl2, loss of zebrafish prickle1a
      decreases fibronectin protein levels in gastrula embryos. We further show that
      Prickle1a physically binds Vangl2 and regulates both the subcellular distribution
      and total protein level of Vangl2. These data suggest that the ability of
      Prickle1a to impact fibronectin organization is at least partly due to effects on
      Vangl2. In contrast to loss of either Vangl2 or Prickle1a function, we find that
      glypican4 (a Wnt co-receptor) and frizzled7 mutant gastrula embryos with
      disrupted non-canonical Wnt signaling exhibit the opposite phenotype, namely
      increased fibronectin assembly. Our data show that glypican4 mutants do not have
      decreased proteolysis of ECM substrates, but instead have increased cell surface
      cadherin protein expression and increased intercellular adhesion. These data
      indicate that Wnt/Glypican4/Frizzled signaling regulates ECM assembly through
      effects on cadherin-mediated cell cohesion. Together, our results demonstrate
      that zebrafish Vangl2/Prickle1a and non-canonical Wnt/Frizzled signaling have
      opposing effects on ECM organization underlying PCP and gastrulation cell
      movements. 

PMID- 24021483
TI  - Body mass index or waist circumference: which is the better predictor for
      hypertension and dyslipidemia in overweight/obese children and adolescents?
      Association of cardiovascular risk related to body mass index or waist
      circumference.
AB  - BACKGROUND: In order to assess the relationship between hypertension or
      dyslipidemia and obesity, the body mass index (BMI) is usually used. Unlike waist
      circumference (WC), BMI does not reflect body fat distribution. The aim of this
      study is to investigate whether BMI or WC is a better predictor of hypertension
      or dyslipidemia in overweight/obese children and adolescents. METHODS: As of
      November 2012, the APV database contained data on 81,819 patients from 189
      specialized pediatric obesity institutions in Germany, Austria and Switzerland.
      Logistic regression analysis was conducted using odds ratios (OR) with 95% CI.
      RESULTS: The average age of the youths (n = 5.978) was 13.9 +/- 1.8 years. Mean
      BMI-SDS was 2.0 +/- 0.5, and mean WC-SDS was 2.2 +/- 0.5. Both BMI-SDS and WC-SDS
      are significant predictors of hypertension and dyslipidemia: BMI-SDS is a better
      predictor (OR = 2.60) for hypertension than WC-SDS (OR = 1.85), while WC-SDS (OR
      = 1.90) was slightly superior to BMI-SDS (OR = 1.86) in predicting adverse lipid
      profiles. Compared to normal-weight patients, obese patients (BMI >= 97th
      percentile) exhibited increased systolic (+6.3 mm Hg) and diastolic blood
      pressure (+3.9 mm Hg). However, this difference was only +4.8 mm Hg (systolic)
      and +2.6 mm Hg (diastolic) if WC >97th percentile was used. CONCLUSION: BMI-SDS
      is more closely associated with hypertension, while WC-SDS is more closely
      associated with dyslipidemia. However, the additional measurement of WC has only
      a small benefit in obese youths.

PMID- 24021484
TI  - Investigation of a prolonged Group A Streptococcal outbreak among residents of a
      skilled nursing facility, Georgia, 2009-2012.
AB  - BACKGROUND: Group A Streptococcus (GAS) is an important bacterial cause of life
      threatening illness among the elderly. Public health officials investigated a
      protracted GAS outbreak in a skilled nursing facility in Georgia housing patients
      requiring 24-hour nursing or rehabilitation, to prevent additional cases.
      METHODS: We defined a case as illness in a skilled nursing facility resident with
      onset after January 2009 with GAS isolated from a usually sterile (invasive) or
      nonsterile site (noninvasive). Cases were "recurrent" if >1 month elapsed between
      episodes. We evaluated infection control practices, performed a GAS carriage
      study, emm-typed available GAS isolates, and conducted a case-control study of
      risk factors for infection. RESULTS: Three investigations, spanning 36 months,
      identified 19 residents with a total of 24 GAS infections: 15 invasive (3
      recurrent) and 9 noninvasive (2 recurrent) episodes. All invasive cases required
      hospitalization; 4 patients died. Seven residents were GAS carriers. All invasive
      cases and resident carrier isolates were type emm 11.0. We observed hand hygiene
      lapses, inadequate infection documentation, and more frequent wound care staff
      turnover on wing A versus wing B. Risk factors associated with infection in
      multivariable analysis included living on wing A (odds ratio [OR], 3.4; 95%
      confidence interval [CI], .9-16.4) and having an indwelling line (OR, 5.6; 95%
      CI, 1.2-36.4). Cases ceased following facility-wide chemoprophylaxis in July
      2012. CONCLUSIONS: Staff turnover, compromised skin integrity in residents, a
      suboptimal infection control program, and lack of awareness of infections likely
      contributed to continued GAS transmission. In widespread, prolonged GAS outbreaks
      in skilled nursing facilities, facility-wide chemoprophylaxis may be necessary to
      prevent sustained person-to-person transmission.

PMID- 24021485
TI  - High rate of schistosomiasis in travelers after a brief exposure to the high
      altitude Nyinambuga crater lake, Uganda.
AB  - Travel-related schistosomiasis is usually associated with prolonged freshwater
      exposure. Until recently, Uganda's crater lakes were considered schistosomiasis
      free due to their high-altitude location. We describe an outbreak of acute
      schistosomiasis after a brief exposure (mean, 22 +/- 9.5 minutes) to a high
      altitude crater lake. 

PMID- 24021486
TI  - Complete endoscopic/transgastric retrieval of eroded gastric band: a novel
      technique.

PMID- 24021487
TI  - Endoscopic closure of gastric perforation using over-the-scope clip: a surgery
      sparing approach.

PMID- 24021488
TI  - Minimally invasive autopsy by using postmortem endoluminal and transluminal
      endoscopy and EUS.
AB  - BACKGROUND: Virtual autopsy by using CT imaging has been introduced as an
      alternative to conventional autopsy and has resulted in an increase in acceptance
      of autopsy by relatives. Because direct inspection and tissue acquisition is not
      possible by imaging alone, various endoscopic techniques can be considered of
      complementary usefulness. OBJECTIVES: We present the first series of sequential
      endoscopic techniques including natural orifice transluminal access for minimally
      invasive autopsy. SETTING: University hospital, legal medicine department.
      SUBJECTS: Twenty deceased subjects. INTERVENTION: Various flexible endoscopic
      modalities including EUS, with biopsy or EUS-guided FNA, were attempted. This
      included transluminal intra-abdominal endoscopic exploration with tissue sampling
      in a few cases. MAIN OUTCOME MEASUREMENTS: Completeness of inspection of the
      luminal and extraluminal cavity as well as tissue acquisition. RESULTS: Complete
      upper GI endoscopy was performed in 17 of 20 and EUS in 8 of 8 cases. In
      addition, transgastric intra-abdominal endoscopy was successfully performed in 5
      cases. Adequate histology from biopsy and EUS-guided puncture could be obtained
      in case of short time intervals post mortem. In 1 case, a rupture of the gastric
      cardia with bleeding was diagnosed as a significant unexpected finding. New minor
      pathological findings were revealed on EGD (6/17), GI EUS (3/8), and transgastric
      inspection (4/5). LIMITATIONS: Limited number of cases for all procedures.
      CONCLUSION: Minimally invasive autopsy by using multiple endoscopic techniques
      for imaging and tissue acquisition is feasible. The significant value of this
      technique, in combination with virtual autopsy compared with classic autopsy,
      warrants further evaluation.

PMID- 24021489
TI  - Biliary stricture secondary to portal biliopathy.

PMID- 24021490
TI  - Transpapillary dilation of refractory severe biliary stricture or main pancreatic
      duct by using a wire-guided diathermic dilator (with video).

PMID- 24021491
TI  - Techniques of endoscopic submucosal dissection: application for the Western
      endoscopist?

PMID- 24021492
TI  - Impact of a computer-based teaching module on characterization of diminutive
      colon polyps by using narrow-band imaging by non-experts in academic and
      community practice: a video-based study.
AB  - BACKGROUND: Experts can accurately characterize the histology of diminutive
      polyps with narrow-band imaging (NBI). There are limited data on the performance
      of non-experts. OBJECTIVE: To assess the impact of a computer-based teaching
      module on the accuracy of predicting polyp histology with NBI by non-experts (in
      academics and community practice) by using video clips. DESIGN: Prospective,
      observational study. SETTING: Academic and community practice. PARTICIPANTS: A
      total of 15 gastroenterologists participated-5 experts in NBI, 5 non-experts in
      academic practice, and 5 non-experts in community practice. INTERVENTION:
      Participants reviewed a 20-minute, computer-based teaching module outlining the
      different NBI features for hyperplastic and adenomatous polyps. MAIN OUTCOME
      MEASUREMENTS: Performance characteristics in characterizing the histology of
      diminutive polyps with NBI by using short video clips before (pretest) and after
      (posttest) reviewing the teaching module. RESULTS: Non-experts in academic
      practice showed a significant improvement in the sensitivity (54% vs 79%; P <
      .001), accuracy (64% vs 81%; P < .001), and proportion of high-confidence
      diagnoses (49% vs 69%; P < .001) in the posttest. Non-experts in community
      practice had significantly higher sensitivity (58% vs 75%; P = .004), specificity
      (76% vs 90%; P = .04), accuracy (64% vs 81%; P < .001), and proportion of high
      confidence diagnoses (49% vs 72%; P < .001) in the posttest. Performance of
      experts in NBI was significantly better than non-experts in both academic and
      community practice. LIMITATIONS: Selection bias in selecting good quality videos.
      Performance not assessed during live colonoscopy. CONCLUSION: Academic and
      community gastroenterologists without prior experience in NBI can achieve
      significant improvements in characterizing diminutive polyp histology after a
      brief computer-based training. The durability of these results and applicability
      in everyday practice are uncertain.

PMID- 24021493
TI  - Glial cells as primary therapeutic targets for epilepsy.
AB  - Neurons have been the natural focus of discussion for most of the history of
      research on seizures and epilepsy. Simply stated, epilepsy is a disease of
      sporadic, progressive disruption of neuronal activity. Thus causes and therapies
      for epilepsy have been naturally aimed at the obvious manifestation of disease:
      neuronal dysfunction. However, over the last two decades a new view is beginning
      to emerge that is defining the dependence of neuronal function and seizure
      susceptibility on glia. This view changes the definition of epilepsy as a disease
      of neurons to a disease of a heterogeneous neuronal-glial network. This new glial
      focus is suggesting new opportunities to treat the nearly 1/3 of individuals who
      do not respond to traditional antiepileptic drug (AEDs) therapies as well as
      suggesting ways to reduce the many unwanted side effects of AEDs. 

PMID- 24021494
TI  - Clinical significance of complement as a biomarker of disease activity in 4 cases
      of IgG4-related disease with retroperitoneal fibrosis.
AB  - Hypocomplementaemia is frequently observed in IgG4-related diseases, however the
      clinical significance is unclear. We describe herein the clinical courses of 4
      patients with IgG4-related disease with hypocomplementaemia. Our cases showed
      autoimmune pancreatitis, retroperitoneal fibrosis, Mikulicz's disease,
      interstitial lung disease, lymphadenopathy and mesenteric fibrosis around the
      aorta. A decrease in serum complement preceded deterioration of the disease and
      clinical improvement was observed in accordance with normalisation of serum
      complement. These clinical courses suggest that serum complement is a biomarker
      of the disease activity. 

PMID- 24021495
TI  - Diagnosis of probable psychogenic nonepileptic seizures in the outpatient clinic:
      does gender matter?
AB  - Psychogenic nonepileptic seizures (PNESs) are paroxysmal events of altered
      behavior that outwardly resemble epilepsy but are caused by psychiatric disease.
      The diagnosis of probable PNESs can be made in the outpatient clinic prior to
      video-EEG monitoring by identification of specific PNES predictors and specific
      elements of seizure semiology from the clinical history. Since psychiatric
      disease may have distinct mechanisms between women and men, the objective of this
      study was to determine if gender-specific differences exist in PNES predictors
      and PNES semiology. Such differences could be used to optimize the accuracy of
      outpatient diagnosis of probable PNESs. Medical records of male and female
      patients with video-EEG diagnosis of definite PNESs were retrospectively reviewed
      for occurrence of PNES predictors. In addition, PNES semiology was analyzed de
      novo from video-EEG records and categorized into previously established semiology
      clusters. Eighty-six patients were included in the analysis (59 women and 27
      men). We found significantly lower rates of reported physical and sexual abuse,
      lower rates of previous psychiatric diagnosis, and lower rates of chronic pain in
      male patients with no significant differences in rates of other PNES predictors.
      Furthermore, we found no difference in PNES semiology between men and women, with
      both groups experiencing similar rates of major motor, minor motor, and nonmotor
      semiology. In conclusion, our results lend support to the idea that distinct risk
      factor criteria but similar semiology criteria should be used for the diagnosis
      of probable PNESs in the outpatient clinic in men and women. 

PMID- 24021496
TI  - Impact of the number of parents with alcohol use disorder on alcohol use disorder
      in offspring: a population-based study.
AB  - OBJECTIVE: Although parental alcohol use disorder (AUD) increases risk for
      alcohol problems in offspring, no studies have evaluated the odds of AUD in
      offspring based on the number of biological parents with AUD (0, 1, or 2) in a
      population-based national sample. The purpose of this study was to investigate
      the relationship between the number of AUD parents and prevalence of AUD in
      offspring. METHOD: This study utilized data from the 2001-2002 National
      Epidemiologic Survey on Alcohol and Related Conditions, which assessed AUD using
      the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV
      Version (main outcome variable). We analyzed the sample (n = 40,374) to
      investigate the effect of the number of AUD parents on lifetime AUD in offspring.
      In a subgroup analysis, gender differences were examined. RESULTS: 22% of adults
      in the United States had at least 1 biological parent with AUD. Compared with
      offspring of non-AUD parents, offspring of 1 AUD parent had a 2.5-fold increase
      (AOR = 2.51; 95% CI, 2.38-2.66) and offspring of 2 AUD parents had a 4.4-fold
      increase (AOR = 4.44; 95% CI, 3.93-5.02) in the odds of lifetime AUD. Each
      additional AUD parent increased the odds of AUD in offspring in an additive
      pattern. Female offspring were more vulnerable to the impact of parental AUD than
      male offspring (OR = 1.17 in offspring of 1 AUD parent; OR = 1.48 in offspring of
      2 AUD parents). CONCLUSIONS: Offspring of AUD parents had heightened odds of
      lifetime AUD, with an additive parental effect. Awareness of this risk can be
      useful for clinicians to educate individuals with AUD parents about prevention
      and intervention.

PMID- 24021497
TI  - A randomized controlled trial of the efficacy and safety of lisdexamfetamine
      dimesylate as augmentation therapy in adults with residual symptoms of major
      depressive disorder after treatment with escitalopram.
AB  - OBJECTIVE: Evaluate the efficacy and safety of lisdexamfetamine dimesylate
      augmentation for major depressive disorder (MDD) in escitalopram nonremitters.
      METHOD: In this proof-of-concept study (conducted from July 2009-August 2010)
      with a prespecified critical alpha = .10, adults with nonpsychotic MDD (DSM-IV-TR
      criteria) and residual depressive symptoms (17-item Hamilton Depression Rating
      Scale score >= 4) after 8 weeks of open-label escitalopram were randomized to 6
      weeks of lisdexamfetamine dimesylate (20-50 mg/d) or placebo augmentation. The
      primary endpoint, Montgomery-Asberg Depression Rating Scale (MADRS) total score
      change in escitalopram nonremitters (MADRS total score > 10) from week 8
      (augmentation baseline) to week 14/end of study, was assessed using analysis of
      covariance, with last observation carried forward. RESULTS: For nonremitters
      (placebo, n = 64; lisdexamfetamine dimesylate, n = 65), the least squares (LS)
      mean (90% CI) treatment difference for MADRS total score reduction at week 14/end
      of study (-2.3 [-4.5 to -0.1]; P = .0902) met the prespecified criterion for
      lisdexamfetamine dimesylate superiority (adjusted effect size, -0.3); the number
      needed to treat for MADRS remission (MADRS total score <= 10) was 6.7. The LS
      mean treatment difference in remitters was not statistically significant (1.2 [
      1.6 to 4.0]; P = .4726). Among randomized participants, 49.4% (42/85) receiving
      placebo and 60.2% (53/88) receiving lisdexamfetamine dimesylate had >= 1
      treatment-emergent adverse event, the most frequent with lisdexamfetamine
      dimesylate being dry mouth and headache (both 11.4%). Mean (SD) vital sign and
      electrocardiogram changes (placebo vs lisdexamfetamine dimesylate) were 0.5
      (8.98) versus 2.3 (9.04) mm Hg (systolic blood pressure), -1.0 (7.19) versus 0.9
      (6.61) mm Hg (diastolic blood pressure), -0.4 (7.39) versus 4.8 (8.64) beats per
      minute (heart rate), and -1.6 (11.23) versus -4.9 (11.84) milliseconds
      (Fridericia-adjusted QTc). CONCLUSIONS: Lisdexamfetamine dimesylate augmentation
      reduced depressive symptoms in participants with inadequate escitalopram
      response. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00905424.

PMID- 24021499
TI  - The law of diminishing intent: getting excited about apathy.

PMID- 24021498
TI  - Safety and efficacy of methylphenidate for apathy in Alzheimer's disease: a
      randomized, placebo-controlled trial.
AB  - OBJECTIVE: In a recent crossover trial, methylphenidate treatment decreased
      apathy in Alzheimer's disease. We further assessed this finding in the Apathy in
      Dementia Methylphenidate Trial (ADMET). METHOD: Six-week, randomized, double
      blind, placebo-controlled multicenter trial enrolling Alzheimer's disease
      participants (NINCDS-ADRDA criteria) with apathy assigned to methylphenidate 20
      mg daily or placebo, conducted from June 2010 to December 2011. Primary outcomes
      were change in Apathy Evaluation Scale (AES) score and modified Alzheimer's
      Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGI-C).
      Secondary outcomes included change in Neuropsychiatric Inventory (NPI) apathy
      score, Mini-Mental State Examination (MMSE) score, and safety. RESULTS: 60
      participants were randomly assigned (29 methylphenidate, 31 placebo). At
      baseline, mean (SD) age = 76 (8) years, MMSE score = 20 (5), AES score = 51 (12),
      NPI total score = 16 (8), and 62% of the participants (n = 37) were female. After
      6 weeks' treatment, mean (SD) change in AES score was -1.9 (1.5) for
      methylphenidate and 0.6 (1.4) for placebo (P = .23). Odds ratio for improvement
      in ADCS-CGI-C was 3.7 (95% CI, 1.3 to 10.8) (P = .02), with 21% of
      methylphenidate versus 3% of placebo rated as moderately or markedly improved.
      NPI apathy score improvement was 1.8 points (95% CI, 0.3 to 3.4) greater on
      methylphenidate than on placebo (P = .02). MMSE trended toward improvement on
      methylphenidate (P = .06). There were trends toward greater anxiety and weight
      loss > 2% in the methylphenidate-treated group. CONCLUSIONS: Methylphenidate
      treatment of apathy in Alzheimer's disease was associated with significant
      improvement in 2 of 3 efficacy outcomes and a trend toward improved global
      cognition with minimal adverse events, supporting the safety and efficacy of
      methylphenidate treatment for apathy in Alzheimer's disease. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT01117181.

PMID- 24021500
TI  - Treatment, bereavement, and trauma in children.

PMID- 24021501
TI  - A randomized placebo-controlled trial of electroencephalographic (EEG)
      neurofeedback in children with attention-deficit/hyperactivity disorder.
AB  - OBJECTIVE: A double-blind, randomized, placebo-controlled study was designed to
      assess the efficacy and safety of electroencephalographic (EEG) neurofeedback in
      children with attention-deficit/hyperactivity disorder (ADHD). The study started
      in August 2008 and ended in July 2012 and was conducted at Karakter Child and
      Adolescent Psychiatry University Centre in Nijmegen, The Netherlands. METHOD:
      Forty-one children (aged 8-15 years) with a DSM-IV-TR diagnosis of ADHD were
      randomly assigned to treatment with either EEG neurofeedback (n = 22) or placebo
      neurofeedback (n = 19) for 30 sessions, given as 2 sessions per week. The
      children were stratified by age, electrophysiologic state of arousal, and
      medication use. Everyone involved in the study, except the neurofeedback
      therapist and the principal investigator, was blinded to treatment assignment.
      The primary outcome was severity of ADHD symptoms on the ADHD Rating Scale IV,
      scored at baseline, during treatment, and at study end. Clinical improvement as
      measured by the Clinical Global Impressions-Improvement scale (CGI-I) was a
      secondary outcome. RESULTS: While total ADHD symptoms improved over time in both
      groups (F1,39 = 26.56, P < .001), there was no significant treatment effect, ie,
      group * time interaction (F1,39 = 0.36, P = .554); the same was true for clinical
      improvement as measured by the CGI-I (P = .092). No clinically relevant side
      effects were observed. Among the children and their parents, guessing treatment
      assignment was not better than chance level (P = .224 for children, P = .643 for
      parents). CONCLUSION: EEG neurofeedback was not superior to placebo neurofeedback
      in improving ADHD symptoms in children with ADHD. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier: NCT00723684.

PMID- 24021502
TI  - Alcohol and substance abuse in parentally bereaved youth.
AB  - OBJECTIVE: Little is known about the role of parental bereavement regarding
      alcohol and substance abuse. Our aim was to examine whether the incidence of
      alcohol and substance abuse is higher in parentally bereaved youth and, if so,
      what might explain this increased incidence. METHOD: In a longitudinal population
      based study conducted between November 2002 and December 2012, the incidence of
      alcohol and substance abuse or dependence (ASAD) during a period of 5 years was
      examined (using DSM-IV criteria) in 235 youth whose parents died of suicide,
      accident, or sudden natural death and 178 demographically similar nonbereaved
      youth. RESULTS: In a period that covered 5 years subsequent to the death,
      bereaved youth had an increased incidence and earlier time to onset of ASAD
      relative to nonbereaved controls (incident rate ratio = 2.44; 95% CI, 1.17-5.56).
      Additionally, youth over the age of 13 years (hazard ratio [HR] = 6.68; 95% CI,
      3.22-13.89; P < .001), those who developed a disruptive behavior disorder (HR =
      7.55; 95% CI, 1.83-31.22; P = .005), and those who had greater functional
      impairment (HR = 0.93; 95% CI, 0.90-0.95; P < .001) were at increased risk for
      ASAD. However, after adjusting for the above-noted variables, the relationship
      between parental bereavement and pathological youth alcohol and substance use was
      not statistically significant (HR = 1.73; 95% CI, 0.79-3.81; P = .17).
      CONCLUSIONS: Bereaved youth are at greater risk for ASAD than their nonbereaved
      counterparts, especially adolescent boys with disruptive behavior disorders. The
      effect of bereavement was explained by its overall impact on greater functional
      impairment in bereaved offspring. Interventions that help to improve offspring
      functioning and that prevent or attenuate the development of disruptive behavior
      disorders have the potential to prevent ASAD in bereaved youth.

PMID- 24021503
TI  - A prospective study of parentally bereaved youth, caregiver depression, and body
      mass index.
AB  - OBJECTIVE: To examine the relationship between body mass index (BMI) in bereaved
      youth and nonbereaved controls 5 years after a parent's death. The study was
      conducted from August 9, 2002, through December 31, 2013. DESIGN: A prospective,
      longitudinal, controlled study of the effects of sudden parental death on youth.
      SETTING: Bereaved families were recruited through coroner records and by
      advertisement. Nonbereaved families were recruited using random-digit dialing and
      by advertisement. PARTICIPANTS: 123 parentally bereaved offspring were compared
      with 122 nonbereaved control offspring, all of whom were aged 11-25 years at the
      5-year assessment. MAIN EXPOSURE: Bereavement status, type of parental death
      (accident, suicide, or sudden natural death), and history of depression in
      caregivers prior to parental death. OUTCOME MEASURES: BMI categories (normal,
      overweight, and obese), according to International Obesity Task Force guidelines
      for adults and Centers for Disease Control and Prevention guidelines for
      children, and DSM-IV psychiatric disorder in offspring and caregivers before and
      after time of parental death. RESULTS: Bereaved offspring were more likely to
      have a BMI in the obese range compared to nonbereaved controls (chi2(2) = 7.13, P
      < .01). There were no differences in BMI category by death type among bereaved
      offspring. Caregiver history of depression was a significant correlate of
      offspring obesity in nonbereaved youth but had a protective effect on the BMI of
      bereaved youth. CONCLUSIONS: Bereaved youth were more likely to be obese than
      nonbereaved youth 5 years after parental death, and caregiver history of
      depression was associated with increased risk for obesity in nonbereaved youth
      only. Future studies are necessary to identify mechanisms that increase risk for
      obesity in parentally bereaved youth.

PMID- 24021504
TI  - Clinical significance of a proposed developmental trauma disorder diagnosis:
      results of an international survey of clinicians.
AB  - OBJECTIVE: Maltreatment, family violence, and disruption in primary caregiver
      attachment in childhood may constitute a developmental form of trauma that places
      children at risk for multiple psychiatric and medical diagnoses that often are
      refractory to well-established evidence-based mental health treatments. No
      integrative diagnosis exists to guide assessment and treatment for these children
      and adolescents. This study therefore assessed clinicians' ratings of the
      clinical utility of a proposed developmental trauma disorder diagnostic
      framework. METHOD: An Internet survey was conducted with an international
      convenience sample of 472 self-selected medical, mental health, counseling, child
      welfare, and education professionals. Respondents made quantitative ratings of
      the clinical significance of developmental trauma disorder, developmental trauma
      exposure, and symptom items and also posttraumatic stress disorder (PTSD) and
      other Axis I internalizing and externalizing disorder symptom items for 4
      clinical vignettes. Ratings of the discriminability of each developmental trauma
      disorder item from PTSD, other anxiety disorders, affective disorders, and
      externalizing behavior disorders, and of each developmental trauma disorder
      item's amenability to existing evidence-based treatments for those disorders,
      also were obtained. RESULTS: Respondents viewed developmental trauma disorder
      criteria as (1) comparable in clinical utility to criteria for PTSD and other
      psychiatric disorders; (2) discriminable from and not fully accounted for by
      other disorders; and (3) refractory to existing evidence-based psychotherapeutic
      treatments. CONCLUSIONS: The exposure and symptom criteria proposed for a
      developmental trauma disorder diagnosis warrant clinical dissemination and
      scientific field testing to determine their actual clinical utility in treating
      traumatized children with complex psychiatric presentations.

PMID- 24021505
TI  - Pulsed intravenous administration of scopolamine produces rapid antidepressant
      effects and modest side effects.

PMID- 24021506
TI  - Toward rational use of benzodiazepines in posttraumatic stress disorder.

PMID- 24021507
TI  - Dr. Lund and colleagues reply.

PMID- 24021508
TI  - Dr. Capehart replies.

PMID- 24021509
TI  - Apparent discrepancy between published study of gabapentin treatment and internal
      company report.

PMID- 24021510
TI  - Dr. Vieta replies.

PMID- 24021514
TI  - Levothyroxine in psychiatry: issues related to absorption after oral dosing.

PMID- 24021515
TI  - Impairment of executive function and attention predicts onset of affective
      disorder in healthy high-risk twins.
AB  - OBJECTIVE: To investigate whether measures of cognitive function can predict
      onset of affective disorder in individuals at heritable risk. METHOD: In a high
      risk study, 234 healthy monozygotic and dizygotic twins with and without a co
      twin history of affective disorder (high- and low-risk twins, respectively) were
      identified through nationwide registers and assessed at baseline using the
      Schedules for Clinical Assessment in Neuropsychiatry, the 17-item Hamilton
      Depression Rating Scale (HDRS), and the cognitive tests Trail Making Test Parts A
      and B, the Stroop test, and the Cambridge Cognitive Examination-Revised (CAMCOR).
      Participants were followed longitudinally at 6-month intervals for up to 9 years
      and finally reassessed with a personal interview to obtain information on whether
      they had developed psychiatric illness. The study was conducted between 2003 and
      2012. RESULTS: 36 participants (15.4%) developed psychiatric disorder, mainly
      affective and anxiety disorders (31 diagnoses) (ICD-10). Onset was predicted by
      decreased executive function as reflected by performance on the Trail Making Test
      A - B (hazard ratio [HR] = 1.02; 95% CI, 1.00-1.03) when adjusted for sex, age,
      years of education and HDRS score at baseline. Reduced global cognitive function
      as indicated by a lower CAMCOR score at baseline showed a trend toward an
      association with subsequent illness onset (P = .08). With regard to the 5 CAMCOR
      subscales, lower scores on attention (HR = 0.71; 95%, CI, 0.54-0.94) and language
      (HR = 0.76; 95% CI, 0.58-0.99) were significantly associated with subsequent
      illness onset. CONCLUSIONS: Among healthy individuals at heritable risk for
      affective disorder, discrete cognitive deficits, especially within executive
      function and attention, seem to predict subsequent onset of affective illness.

PMID- 24021516
TI  - An evidence synthesis of care models to improve general medical outcomes for
      individuals with serious mental illness: a systematic review.
AB  - OBJECTIVE: To conduct a systematic review of studies of interventions that
      integrated medical and mental health care to improve general medical outcomes in
      individuals with serious mental illness. DATA SOURCES: English-language
      publications in MEDLINE (via PubMed), EMBASE, PsycINFO, and the Cochrane Library,
      from database inception through January 18, 2013, were searched using terms for
      our diagnoses of interest, a broad set of terms for care models, and a set of
      terms for randomized controlled trials (RCTs) or quasi-experimental design.
      Bibliographies of included articles were examined for additional sources.
      ClinicalTrials.gov was searched using the terms for our diagnoses of interest
      (serious mental illness,SMI,bipolar disorder,schizophrenia,orschizoaffective
      disorder) to assess for evidence of publication bias and ongoing studies. STUDY
      SELECTION: 4 RCTs were included from 1,729 articles reviewed. Inclusion criteria
      were RCT or quasi-experimental design; adult outpatient population with 25% or
      greater carrying a diagnosis of schizophrenia, schizoaffective disorder, or
      bipolar disorder; intervention with a stated goal to improve medical outcomes
      through integration of care, using a comparator of usual care or other quality
      improvement strategy; and outcomes assessing process of care, clinical outcomes,
      or physical functioning. DATA EXTRACTION: A trained researcher abstracted the
      following data from the included articles: study design, funding source, setting,
      population characteristics, eligibility and exclusion criteria, number of
      subjects and providers, intervention(s), comparison(s), length of follow-up, and
      outcome(s). These abstracted data were then overread by a second reviewer.
      RESULTS: Of the 4 studies reviewed, 2 good-quality studies (according to the
      guidelines of the Agency for Healthcare Research and Quality) that evaluated
      processes of preventive and chronic disease care demonstrated positive effects of
      integrated care. Specifically, integrated care interventions were associated with
      increased rates of immunization and screening. All 4 RCTs evaluated changes in
      physical functioning, with mixed results: 2 studies demonstrated small
      improvements in the physical health component of the 36-Item Short-Form Health
      Survey (SF-36) and the 12-Item Short-Form Health Survey, and 2 studies
      demonstrated no significant difference in SF-36 scores. No studies reported on
      clinical outcomes related to preventive care or chronic medical care.
      CONCLUSIONS: Integrated care models have positive effects on processes of
      preventive and chronic disease care but have inconsistent effects on physical
      functioning for individuals with serious mental illness. The relatively small
      number of trials and limited range of treatment models tested and outcomes
      reported point to the need for additional study in this important area.

PMID- 24021517
TI  - Impact of physiologic estrogen replacement on anxiety symptoms, body shape
      perception, and eating attitudes in adolescent girls with anorexia nervosa: data
      from a randomized controlled trial.
AB  - OBJECTIVE: Anorexia nervosa is characterized by low weight, aberrant eating
      attitudes, body image distortion, and hypogonadism. Anxiety is a common comorbid
      condition. Estrogen replacement reduces anxiety in animal models, and reported
      variations in food intake across the menstrual cycle may be related to gonadal
      steroid levels. The impact of estrogen replacement on anxiety, eating attitudes,
      and body image has not been reported in anorexia nervosa. We hypothesized that
      physiologic estrogen replacement would ameliorate anxiety and improve eating
      attitudes without affecting body image in anorexia nervosa. METHOD: Girls 13-18
      years old with anorexia nervosa (DSM-IV) were randomized to transdermal estradiol
      (100 MUg twice weekly) with cyclic progesterone or placebo patches and pills for
      18-months, between 2002 and 2010. The State-Trait Anxiety Inventory for Children
      (STAIC), the Eating Disorders Inventory-2 (EDI-2), and the Body Shape
      Questionnaire (BSQ-34) were administered. 72 girls completed these measures at
      baseline (n=38 [girls receiving estrogen] and n=34 [girls receiving placebo]) and
      37 at 18 months (n=20 [girls receiving estrogen] and n=17 [girls receiving
      placebo]). The primary outcome measure was the change in these scores over 18
      months. RESULTS: Estrogen replacement caused a decrease in STAIC-trait scores (
      3.05 [1.22] vs. 2.07 [1.73], P=.02), without impacting STAIC-state scores (-1.11
      [2.17] vs. 0.20 [1.42], P=.64). There was no effect of estrogen replacement on
      EDI-2 or BSQ-34 scores. Body mass index (BMI) changes did not differ between
      groups, and effects of estrogen replacement on STAIC-trait scores persisted after
      controlling for BMI changes (P=.03). Increases in serum estradiol were
      significantly associated with decreases in STAIC-trait scores (Spearman rho = 
      0.45, P=.03). CONCLUSIONS: Estrogen replacement improved trait anxiety (the
      tendency to experience anxiety) but did not impact eating attitudes or body shape
      perception. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00088153.

PMID- 24021518
TI  - A multicenter, randomized, double-blind, placebo-controlled study of aripiprazole
      in children and adolescents with Tourette's disorder.
AB  - OBJECTIVE: To examine the short-term efficacy and tolerability of aripiprazole
      for children and adolescents with Tourette's disorder. METHOD: This 10-week
      multicenter, double-blind, randomized, placebo-controlled trial was conducted
      from August 2008 to April 2010. Children and adolescents (aged 6-18 years) with a
      DSM-IV diagnosis of Tourette's disorder and a Yale Global Tic Severity Scale
      total tic score of 22 or more were randomly assigned (1:1 ratio) to placebo or
      aripiprazole. The primary outcome measure was mean change from baseline in the
      total tic score on the Yale Global Tic Severity Scale (last observation carried
      forward). Assessments of safety and tolerability included spontaneously reported
      adverse events, extrapyramidal symptoms, serum prolactin level, metabolic
      variables, and other laboratory evaluations. RESULTS: Of 61 subjects, 89%
      completed the study. Patients who received aripiprazole demonstrated a
      significant reduction from baseline to end of study on the mean (SD) total tic
      score of the Yale Global Tic Severity Scale compared to those who received
      placebo (-15.0 [8.4] and -9.6 [8.8], respectively, P=.0196). Response rate on the
      Tourette's Syndrome Clinical Global Impression-Improvement was 66% and 45% in the
      aripiprazole and placebo groups, respectively. Mean decrease in the Tourette's
      Syndrome Clinical Global Impression-Severity of Illness score was significantly
      different between the groups (P=.0321). In general, aripiprazole was well
      tolerated and there were no early discontinuations due to adverse events. The
      incidence of treatment-emergent adverse events between the groups was not
      significantly different (P=.7550). While aripiprazole decreased serum prolactin
      concentration (P<.0001), it increased mean body weight, body mass index, and
      waist circumference significantly (P=.0055, P=.0142, and P=.0270, respectively).
      CONCLUSIONS: In comparison with placebo, aripiprazole was efficacious, generally
      tolerated and safe in the short-term treatment of children and adolescents with
      Tourette's disorder. TRIAL REGISTRATION: ClinicalTrials.gov
      identifier:NCT00706589.

PMID- 24021519
TI  - A Bayesian framework to assess the potential for controlling classical scrapie in
      sheep flocks using a live diagnostic test.
AB  - Current strategies to control classical scrapie remove animals at risk of scrapie
      rather than those known to be infected with the scrapie agent. Advances in
      diagnostic tests, however, suggest that a more targeted approach involving the
      application of a rapid live test may be feasible in future. Here we consider the
      use of two diagnostic tests: recto-anal mucosa-associated lymphatic tissue
      (RAMALT) biopsies; and a blood-based assay. To assess their impact we developed a
      stochastic age- and prion protein (PrP) genotype-structured model for the
      dynamics of scrapie within a sheep flock. Parameters were estimated in a Bayesian
      framework to facilitate integration of a number of disparate datasets and to
      allow parameter uncertainty to be incorporated in model predictions. In small
      flocks a control strategy based on removal of clinical cases was sufficient to
      control disease and more stringent measures (including the use of a live
      diagnostic test) did not significantly reduce outbreak size or duration. In
      medium or large flocks strategies in which a large proportion of animals are
      tested with either live diagnostic test significantly reduced outbreak size, but
      not always duration, compared with removal of clinical cases. However, the
      current Compulsory Scrapie Flocks Scheme (CSFS) significantly reduced outbreak
      size and duration compared with both removal of clinical cases and all strategies
      using a live diagnostic test. Accordingly, under the assumptions made in the
      present study there is little benefit from implementing a control strategy which
      makes use of a live diagnostic test. 

PMID- 24021520
TI  - Comparing methods for estimating R0 from the size distribution of subcritical
      transmission chains.
AB  - Many diseases exhibit subcritical transmission (i.e. 0<R0<1) so that infections
      occur as self-limited 'stuttering chains'. Given an ensemble of stuttering
      chains, information about the number of cases in each chain can be used to infer
      R0, which is of crucial importance for monitoring the risk that a disease will
      emerge to establish endemic circulation. However, the challenge of imperfect case
      detection has led authors to adopt a variety of work-around measures when
      inferring R0, such as discarding data on isolated cases or aggregating
      intermediate-sized chains together. Each of these methods has the potential to
      introduce bias, but a quantitative comparison of these approaches has not been
      reported. By adapting a model based on a negative binomial offspring distribution
      that permits a variable degree of transmission heterogeneity, we present a
      unified analysis of existing R0 estimation methods. Simulation studies show that
      the degree of transmission heterogeneity, when improperly modeled, can
      significantly impact the bias of R0 estimation methods designed for imperfect
      observation. These studies also highlight the importance of isolated cases in
      assessing whether an estimation technique is consistent with observed data.
      Analysis of data from measles outbreaks shows that likelihood scores are highest
      for models that allow a flexible degree of transmission heterogeneity.
      Aggregating intermediate sized chains often has similar performance to analyzing
      a complete chain size distribution. However, truncating isolated cases is
      beneficial only when surveillance systems clearly favor full observation of large
      chains but not small chains. Meanwhile, if data on the type and proportion of
      cases that are unobserved were known, we demonstrate that maximum likelihood
      inference of R0 could be adjusted accordingly. This motivates the need for future
      empirical and theoretical work to quantify observation error and incorporate
      relevant mechanisms into stuttering chain models used to estimate transmission
      parameters. 

PMID- 24021521
TI  - Population-level differences in disease transmission: a Bayesian analysis of
      multiple smallpox epidemics.
AB  - Estimates of a disease's basic reproductive rate R0 play a central role in
      understanding outbreaks and planning intervention strategies. In many
      calculations of R0, a simplifying assumption is that different host populations
      have effectively identical transmission rates. This assumption can lead to an
      underestimate of the overall uncertainty associated with R0, which, due to the
      non-linearity of epidemic processes, may result in a mis-estimate of epidemic
      intensity and miscalculated expenditures associated with public-health
      interventions. In this paper, we utilize a Bayesian method for quantifying the
      overall uncertainty arising from differences in population-specific basic
      reproductive rates. Using this method, we fit spatial and non-spatial susceptible
      exposed-infected-recovered (SEIR) models to a series of 13 smallpox outbreaks.
      Five outbreaks occurred in populations that had been previously exposed to
      smallpox, while the remaining eight occurred in Native-American populations that
      were naive to the disease at the time. The Native-American outbreaks were close
      in a spatial and temporal sense. Using Bayesian Information Criterion (BIC), we
      show that the best model includes population-specific R0 values. These
      differences in R0 values may, in part, be due to differences in genetic
      background, social structure, or food and water availability. As a result of
      these inter-population differences, the overall uncertainty associated with the
      "population average" value of smallpox R0 is larger, a finding that can have
      important consequences for controlling epidemics. In general, Bayesian
      hierarchical models are able to properly account for the uncertainty associated
      with multiple epidemics, provide a clearer understanding of variability in
      epidemic dynamics, and yield a better assessment of the range of potential risks
      and consequences that decision makers face. 

PMID- 24021522
TI  - Effects of two different exercise programs on gait parameters in individuals with
      Parkinson's disease: a pilot study.
AB  - To date, little attempt has been made to compare or evaluate the effects of
      different physical exercise programs on gait disorders in people with Parkinson's
      disease (PD). This pilot study is aimed at obtaining preliminary data of the
      effects of two different exercise programs on gait parameters in people with PD
      by means of a biomechanical three-dimensional motion analysis. Twenty-five
      individuals with idiopathic PD participated either in a land-based (LB) or in a
      LB plus water-based (LWB) exercise program for 16 weeks. The efficacy of both
      exercise programs was quantified by means of a biomechanical gait analysis from
      which spatiotemporal and sagittal plane kinetic (gait speed, stride length,
      cadence, stride time, simple support time, double support time) and kinematic
      (angles of the hip, knee, and ankle joints) variables were recorded. Once the
      intervention ended, significant changes were observed in stride length and
      single/double support time variables in all the patients. The intergroup analysis
      revealed the existence of significant differences only in the gait Speed and hip
      Angle parameters. Few significant improvements in the amplitude of lower limb
      joints were found. These results suggest that land-based and land-plus-water
      based exercise programs can be considered as a useful physical rehabilitation
      alternative, both equally capable of improving gait impairment on Parkinson's
      disease. 

PMID- 24021523
TI  - Number of test trials needed for performance stability and interrater reliability
      of the one leg stand test in patients with a major non-traumatic lower limb
      amputation.
AB  - INTRODUCTION: Balance is beneficial for daily functioning of patients with a
      lower limb amputation and sometimes assessed by the one-leg stand test (OLST).
      The aims of the study were to examine (1) the number of trials needed to achieve
      performance stability, (2) the interrater reliability of the OLST in patients
      with a major non-traumatic lower limb amputation, and (3) to provide a test
      procedure. METHODS: Thirteen women and 23 men with a mean age (SD) of 67.4 (10.6)
      years; 19 below-knee and 17 above-knee amputees who performed the OLST at a mean
      of 14.5 (4.5) days post-amputation. All patients performed five timed OLST-trials
      with 1-min rest intervals between trials, supervised by a physical therapist, of
      which 28 included in the reliability-part conducted this twice, separated with a
      mean of 3.4 (0.78)h. Repeated measures Friedman determined the number of trials
      needed to ensure stable OLST-scores while the ICC1.1, the standard error of
      measurement (SEM) and the smallest real difference (SRD) determined
      reproducibility. RESULTS: No learning curve was found for the five OLST-trials
      (p=0.241), with the best of the five trials reaching a median (25-75% quartile)
      of 2.9 (1.7-8.2)s, and with only six patients able to stand for more than 10s.
      The ICC (95% CI), SEM and SRD were respectively 0.87 (0.61-0.96), 0.99 s and 2.74
      s. CONCLUSION: Findings suggest that the best of five trials be used for the OLST
      in unilateral non-traumatic amputee patients as we found excellent interrater
      reliability and acceptable agreement when using this score.

PMID- 24021524
TI  - The effect of variability in body segment parameters on joint moment using Monte
      Carlo simulations.
AB  - This study used Monte Carlo methods to simulate the effects of variability and
      uncertainty in inertial body segment parameters (BSPs) on joint torques
      calculated using inverse dynamics. The average and standard deviation values of
      BSPs from previously published studies were used as inputs into the Monte Carlo
      simulation. Data from five groups were evaluated: cadaveric subjects; living
      subjects (Caucasian only); female living subjects (Caucasian only); male living
      subjects (Caucasian only); and living subjects (non-Caucasian). The differences
      in BSPs observed between the different groups were statistically significant;
      however, using BSP variability data from these groups made little difference to
      the calculated joint torques. This suggests that for slow and repeatable movement
      such as walking, BSPs have little effect on joint moments, except for the swing
      phase. Even then, the magnitude of difference in the swing phase due to
      variability in BSPs is not much greater than the inter-trial variability. As
      expected, distal BSPs have little effect on proximal joint moment.

PMID- 24021525
TI  - Effect of armor and carrying load on body balance and leg muscle function.
AB  - This study investigated the impact of weight and weight distribution of body
      armor and load carriage on static body balance and leg muscle function. A series
      of human performance tests were conducted with seven male, healthy, right-handed
      military students in seven garment conditions with varying weight and weight
      distributions. Static body balance was assessed by analyzing the trajectory of
      center of plantar pressure and symmetry of weight bearing in the feet. Leg muscle
      functions were assessed by analyzing the peak electromyography amplitude of four
      selected leg muscles during walking. Results of this study showed that uneven
      weight distribution of garment and load beyond an additional 9 kg impaired static
      body balance as evidenced by increased sway of center of plantar pressure and
      asymmetry of weight bearing in the feet. Added weight on non-dominant side of the
      body created greater impediment to static balance. Increased garment weight also
      elevated peak EMG amplitude in the rectus femoris to maintain body balance and in
      the medial gastrocnemius to increase propulsive force. Negative impacts on
      balance and leg muscle function with increased carrying loads, particularly with
      an uneven weight distribution, should be stressed to soldiers, designers, and
      sports enthusiasts.

PMID- 24021526
TI  - Neck musculature fatigue affects specific frequency bands of postural dynamics
      during quiet standing.
AB  - Proprioceptive input from the neck is important for maintenance of upright
      standing. Although neck musculature fatigue has been demonstrated to impair
      standing balance, there is limited understanding of the underlying postural
      mechanisms. This study aimed to further examine the effects of neck musculature
      fatigue on standing by using modern analysis of center of pressure (CoP) data.
      Forty-eight young healthy adults stood quietly on a balance board for 1 min
      before and after performing repeated weight-resisted scapular elevation
      exercises. In a supplementary study on 20 participants, we examined (i) the
      effects of visual deprivation and (ii) the test-retest reliability of the
      traditional and wavelet-based CoP measures. Test-retest reliability of the CoP
      measures was moderate to good (intraclass correlation coefficients ranged from
      0.58 to 0.94). With neck muscle fatigue or without vision, traditional measures
      of CoP velocity and standard deviation increased monotonically. Wavelet analysis
      revealed that CoP velocity within the ultralow (<0.10 Hz) and moderate (1.56-6.25
      Hz) frequency bands increased post-fatigue. Without vision, CoP velocity
      increased in all but the ultralow frequency band. Our data suggest that post
      fatigue, vision may be the main compensatory postural mechanism for altered neck
      proprioception. In conclusion, our findings reveal more nuances than the simple
      assertion that neck musculature fatigue increased postural sway and they advocate
      the use of wavelet analysis in examining postural mechanisms associated with neck
      proprioception.

PMID- 24021527
TI  - SCIRR39 promotes neurite extension via RhoA in NGF-induced PC12 cells.
AB  - SCIRR39 is an identified upregulated gene in rat primary neuron injury and/or
      regeneration process with roles largely unexplored. Using real-time quantitative
      PCR, Western blotting and immunofluorescence, SCIRR39 expression was detected in
      normal PC12 cells and upregulated in differentiated cells. The results of cell
      proliferation by Cell Counting Kit and cell cycle by flow cytometry indicated
      that SCIRR39 inhibited cell proliferation and induced the decrease in S phase.
      Importantly, immunofluorescent and RhoA pull-down assays showed that SCIRR39
      strongly affected the neurite extension of NGF-treated PC12 cells through a RhoA
      dependent mechanism, but the truncated mutants of SCIRR39 containing a truncation
      from 141AA to 211AA or from 397AA to 424AA failed to mock the SCIRR39 effect on
      neurite extension. Moreover, change of SCIRR39 expression in NGF-treated PC12
      cells regulated the expression and phosphorylation of Fyn, a regulator of RhoA
      activity, but not the expression of ROCK II protein. Finally, immunofluorescence
      and RhoA pull-down assays revealed that obvious inhibition of neurite extension
      by SCIRR39 shRNA was reversed by RhoA inhibitor C3-transferase. Our results
      indicated that SCIRR39 increased the neurite extension in NGF-treated PC12 cells
      via RhoA, suggesting that SCIRR39 contributes to the regeneration of neuron
      injury by specifically altering the differentiation program.

PMID- 24021528
TI  - Impact of environmental tobacco smoke on children with asthma, United States,
      2003-2010.
AB  - OBJECTIVE: Given widespread interventions to reduce environmental tobacco smoke
      (ETS) exposure and improve asthma control, we sought to assess the current impact
      of ETS exposure on children with asthma. METHODS: We analyzed 2003-2010 data for
      nonsmoking children aged 6 to 19 years with asthma from the National Health and
      Nutrition Examination Survey. Outcomes (sleep disturbance, missed school days,
      health care visits, activity limitation, and wheezing with exercise) were
      compared between ETS exposed children (serum cotinine levels 0.05 to 10 ng/mL)
      and unexposed children (<0.05 ng/mL) using ordinal regression adjusted for
      demographic characteristics. We also assessed whether associations were
      observable with low ETS exposure levels (0.05 to 1.0 ng/mL). RESULTS: Overall,
      53.3% of children aged 6 to 19 years with asthma were ETS exposed. Age-stratified
      models showed associations between ETS exposure and most adverse outcomes among 6
      to 11-year-olds, but not 12- to 19-year-olds. Even ETS exposure associated with
      low serum cotinine levels was associated with adverse outcomes for 6- to 11-year
      olds. Race-stratified models for children aged 6 to 19 years showed an
      association between ETS exposure and missing school, health care visits, and
      activity limitation due to wheezing among non-Hispanic white children, and
      disturbed sleep among non-Hispanic white and Mexican children. Among non-Hispanic
      black children, there was no elevated risk between ETS exposure and the assessed
      outcomes: non-Hispanic black children had high rates of adverse outcomes
      regardless of ETS exposure. CONCLUSIONS: Among children with asthma 6 to 11 years
      of age, ETS exposure was associated with most adverse outcomes. Even ETS exposure
      resulting in low serum cotinine levels was associated with risks for young
      children with asthma.

PMID- 24021529
TI  - Child injury control: trends, themes, and controversies.
AB  - Injury is a major cause of morbidity and mortality among US children, and an
      important driver of health status globally. Despite its enormous burden, injury
      is preventable. Over the last 10 years, significant progress has been made in the
      reduction of unintentional injury among US children. However, aggregate trends
      mask important disparities by age group, region, and injury mechanism. Basic and
      translation research is needed to develop and test prevention strategies to
      address these new or recalcitrant problems. Motor vehicle occupant injury has
      fallen to historic lows, but challenges remain in protecting novice drivers and
      managing the distraction of new technologies. Injury to pedestrians has also
      declined, but likely as a result of decreased exposure as fewer children walk.
      This calls for a broader public health perspective to promote activity while
      enhancing safety. Deaths due to drowning are common and illustrate the difficulty
      in measuring and promoting appropriate supervision. Environmental modification
      and use of protective products may be a more appropriate response. Concussion in
      sport is another challenging issue: public health laws promote identification and
      appropriate management of concussed athletes, but less progress has been made on
      primary prevention of these injuries. Unintentional poisoning is on the rise,
      attributable to misuse of, and overdose with, prescription opioids. Injury deaths
      to infants are also increasing. This trend is driven in part by better death
      investigation that classifies more sleep-related deaths as suffocation events.
      Finally, we examine a sample of cross-cutting themes and controversies in injury
      control that might be amenable to empiric evaluation. 

PMID- 24021530
TI  - The effects of high-fat diet, branched-chainamino acids and exercise on female
      C57BL/6 mouse Achilles tendon biomechanical properties.
AB  - OBJECTIVES: The goals of this study were: 1) to determine if high-fat diet (HFD)
      feeding in female mice would negatively impact biomechanical and histologic
      consequences on the Achilles tendon and quadriceps muscle; and 2) to investigate
      whether exercise and branched-chain amino acid (BCAA) supplementation would
      affect these parameters or attenuate any negative consequences resulting from HFD
      consumption. METHODS: We examined the effects of 16 weeks of 60% HFD feeding,
      voluntary exercise (free choice wheel running) and BCAA administration in female
      C57BL/6 mice. The Achilles tendons and quadriceps muscles were removed at the end
      of the experiment and assessed histologically and biomechanically. RESULTS: HFD
      feeding significantly decreased the Achilles tendon modulus without histological
      alterations. BCAA administration significantly decreased the stiffness of
      Achilles tendons in the exercised normal diet mice. Exercise partially
      ameliorated both the weight gain and glucose levels in the HFD-fed mice, led to a
      significant decrease in the maximum load of the Achilles tendon, and an increase
      in the average fibril diameter of the quadriceps femoris muscle. There were
      significant correlations between body weight and several biomechanical
      properties, demonstrating the importance of controlling obesity for maintaining
      healthy tendon properties. CONCLUSIONS: In summary, this study showed a
      significant impact of obesity and body weight on tendon biomechanical properties
      with limited effects of exercise and BCAAs. Cite this article: Bone Joint Res
      2013;2:186-92.

PMID- 24021531
TI  - Intravascular large B cell lymphoma: widespread but not everywhere.

PMID- 24021533
TI  - [Changes in knowledge and carrying out the advance directives of patients
      admitted to internal medicine].
AB  - BACKGROUNDS: Advance directives (ADs), are documents in which patients express in
      advance that their wishes are fulfilled when they are unable to communicate them.
      It is unknown whether patients admitted to internal medicine are more aware of
      and make ADs. OBJECTIVE: To study the changes in the level of knowledge and
      implementation of AD among patients admitted to an internal medicine department
      of a hospital in Madrid since a specific regulation to implement them was
      introduced. PATIENTS AND METHODS: A survey was conducted among patients admitted
      to internal medicine in two periods: 2008 and 2010. RESULTS: A total of 206
      surveys were analysed (84 in 2008 and 122 in 2010). The mean age of the patients
      was 76.8 years, and 51.5% were women. More than two-thirds (69.4%) had a co
      morbidity. and 4.4% had a terminal illness, with no statistical differences
      between the periods. Only 5.3% knew what ADs are, 1 had implemented ADs, and
      46.1%, once informed, would like to implement them. There were no differences
      between 2008 and 2010 as regards knowledge and implementation of AD. In 2010
      there was a greater interest to implement them (would like to implement them:
      52.5 vs 36.9%), although in 2010 less respondents believe that AD would change
      the attitude of the doctor (not change the attitude: 92.6 vs. 69%, P<.001).
      CONCLUSIONS: Knowledge and implementation of AD did not change significantly in
      the years following the regulation (from 2008-2010). In both periods, their
      knowledge and implementation are scarce.

PMID- 24021532
TI  - Identification and characterization of microRNAs in the developing maize
      endosperm.
AB  - MicroRNAs (miRNAs) are non-coding RNAs that are approximately 20-22 nucleotides
      long. miRNAs have been shown to be important regulators that control a large
      variety of biological functions in eukaryotic cells. To investigate the roles of
      miRNAs in maize endosperm development, two small RNA libraries of maize endosperm
      at two developmental stages were sequenced. A total of 17,773,394 and 18,586,523
      small RNA raw reads were obtained, respectively. Further analysis identified and
      characterized 95 known miRNAs belonging to 20 miRNA families. In addition, 18
      novel miRNAs were identified and grouped into 11 families. Potential targets for
      5 of the novel miRNA families were successfully predicted. We had also identified
      12 corresponding miRNAs* of these novel miRNAs. In summary, we investigated
      expression patterns of miRNA in maize endosperm at key developmental stages and
      identified miRNAs that are likely to playing an important role in endosperm
      development. 

PMID- 24021535
TI  - Mechanism of hyperhomocysteinemia-induced vascular endothelium dysfunction -
      possible dysregulation of phosphatidylinositol-3-kinase and its downstream
      phosphoinositide dependent kinase and protein kinase B.
AB  - Imbalance of l-arginine/endothelial nitric oxide synthatase (eNOS) activity is
      the hallmark of vascular endothelium dysfunction. Hyperhomocysteinemia (Hhy) has
      been identified as a potential risk factor for vascular endothelium dysfunction
      that leads to cardiovascular disorders. Phosphatidylinositol-3 kinase (PI3K) is a
      ubiquitous enzyme involved in plethora of cell signaling including the
      endothelial cells and it has been reported that signaling through this enzyme and
      its downstream pathway viz phosphoinositide-dependent kinase (PDK)/protein kinase
      B (Akt) and eNOS is impaired in diseased conditions. Thus present study was
      designed to investigate the role of PI3K and PDK/Akt in vascular endothelium
      dysfunction produced by Hhy. Hhy was produced by administering l-methionine
      (1.7%w/w, p.o). After four weeks of l-methionine administration, vascular
      endothelium dysfunction was assessed in terms of attenuation of acetylcholine
      induced endothelium dependent relaxation (Isolated aortic ring preparation), a
      decrease in serum nitrite level, mRNA expression of eNOS (rtPCR) and disruption
      of integrity of vascular endothelium (Electron microscopy). Administration of
      insulin (0.6 IU/kg/day, s.c), YS-49 (1.6 mg/kg/day, i.p), DAQB1 (5mg/kg/day, i.p)
      and atorvastatin (30 mg/kg/day, p.o) significantly improved acetylcholine-induced
      endothelium-dependent relaxation, serum nitrate/nitrite level, mRNA expression of
      eNOS and integrity of vascular endothelium. This ameliorative effect of insulin
      was blocked by wortmannin (inhibitor of PI3K), UCN-01(PDK inhibitor), API-2 (Akt
      inhibitor) and l-NAME (eNOS inhibitor). Thus, it may be concluded that activation
      of PI3K and its downstream pathways viz. PDK/Akt and eNOS improve Hhy-induced
      vascular endothelium dysfunction and that therapeutic interventions designed for
      these pathways may provide potential therapeutic strategies to combat vascular
      complications.

PMID- 24021534
TI  - [Psychosocial adjustment, psychiatric morbidity and quality of life in
      adolescents and young adults with congenital heart disease].
AB  - OBJECTIVES: We aimed to study the psychosocial adjustment (PSA), psychiatric
      morbidity and quality of life of adolescents and young adults with congenital
      heart disease (CHD) to determine which demographic and clinical variables
      negatively affect adjustment and which increase resilience. METHODS: The study
      included 74 patients with CHD, 41 male and 33 female, aged between 12 and 26
      years (mean 18.76+/-3.86). Demographic information and a complete clinical
      history were obtained. The participants were interviewed regarding social
      support, family environment, self-image and physical limitations. A standardized
      psychiatric interview was conducted, and self-report questionnaires were
      administered for assessment of PSA (Youth Self Report and Adult Self Report) and
      quality of life (World Health Organization Quality of Life - Short Version). A
      caregiver completed an observational version of the PSA questionnaire (Child
      Behavior Checklist or Adult Behavior Checklist). RESULTS: Female participants
      showed more feelings of anxiety and depression (U=952.500; p=0.003), thought
      problems (U=929.500; p=0.005) and aggressive behavior (U=999.000; p=0.000). They
      also showed a higher rate of psychopathology. Patients with complex forms of CHD
      reported more thought problems (U=442.000; p=0.027) and internalization
      (U=429.000; p=0.021). Compared to the Portuguese population as a whole,
      participants showed better quality of life in the domains of social relationships
      (t=2.333; p=0.022) and environment (t=3.754; p=0.000). Patients who had undergone
      surgery had worse quality of life in physical terms (t=-1.989; p=0.050), social
      relationships (t=-2.012; p=0.048) and general quality of life (U=563.000;
      p=0.037), compared to those who were not operated. Better social support was
      associated with better quality of life in physical terms (t=3.287; p=0.002) and
      social relationships (t=3.669; p=0.000). Better school performance was also
      associated with better overall quality of life (U=457.000; p=0.046), less
      withdrawn behavior (U=812.500; p=0.031), fewer feelings of anxiety and depression
      (U=854.000; p=0.009), fewer attention problems (U=903.500; p=0.001), and lower
      scores for internalization (U=817.000; p=0.029) and externalization (U=803.500;
      p=0.042). Physical limitations had a detrimental effect on quality of life
      (U=947.500; p=0.001). DISCUSSION: Female participants were more prone to worse
      psychological adjustment and to psychopathology. Patients with complex forms of
      CHD showed worse PSA, as they need regular care, which restricts social contact
      with peers and family and integration in school and leisure activities. Patients
      who had undergone surgery showed worse quality of life as they often have long
      hospital stays, during which social activities are restricted, making it more
      difficult for them to develop a good social support network. They require close
      medical care, and the restrictions on their activities may be life-limiting.
      Their sense of survival may also be threatened. CONCLUSIONS: Patients with CHD
      appear to be more prone to psychopathology and female patients are more likely to
      show worse PSA. Social support was shown to play a crucial role in buffering
      stress and promoting patients' adjustment.

PMID- 24021536
TI  - Capacities of metabotropic glutamate modulators in counteracting soman-induced
      seizures in rats.
AB  - Current treatment of nerve agent poisoning with ionotropic drugs proves
      inadequate, and alternative treatment strategies are searched for. Based on
      positive findings with metabotropic glutamate modulators in microinfusion
      studies, the present study was initiated to examine anticonvulsant effects of
      MPEP (2-Methyl-6-(phenylethynyl)pyridine hydrochloride), a metabotropic glutamate
      receptor 5 antagonist, and DCG-IV ((2S,2'R,3'R)-2-(2',3'
      dicarboxycyclopropyl)glycine), a metabotropic glutamate receptor 2/3 agonist,
      when administered systemically in combinations with HI-6 (1-[([4
      (aminocarbonyl)pyridino]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium) and
      procyclidine or HI-6 and levetiracetam relative to the combination of HI-6,
      procyclidine, and levetiracetam. The results showed that MPEP or DCG-IV combined
      with HI-6 and procyclidine resulted in substantial antidotal efficacy when
      administered 20 min after onset of seizures elicited by soman. MPEP or DCG-IV
      combined with HI-6 and levetiracetam did not terminate seizures and preserve
      lives. When given 20 min before challenge with soman, DCG-IV in combination with
      HI-6 and procyclidine provided protection, whereas MPEP combined with HI-6 and
      procyclidine did not. Combinations with metabotropic glutamate receptor
      modulators did not achieve the same high level of antidotal efficacy as the
      combination of HI-6, procyclidine, and levetiracetam. MPEP alone inhibited
      pseudocholinesterase activity in the brain markedly. A positive correlation was
      found between latency to seizure onset or full protection and level of
      pseudocholinesterase activity in brain. MPEP and DCG-IV can serve as effective
      anticonvulsants against nerve agent poisoning when combined with HI-6 and
      procyclidine. Metabotropic glutamate receptor modulators may represent an
      alternative or supplement to treatment with ionotropic drugs.

PMID- 24021537
TI  - Didox potentiates the cytotoxic profile of doxorubicin and protects from its
      cardiotoxicity.
AB  - The use of adjuvant therapies in cancer treatment is rationalized by potentiating
      the efficacy and/or protecting from the major side effects of chemotherapeutics.
      Didox, besides its antioxidant properties, is an inhibitor for DNA synthesis and
      repair which might recommend its use as adjuvant therapy. Herein, we have studied
      the effect of didox in potentiating the efficacy of doxorubicin (DOX) against
      liver cancer cells and protecting from its dose-limiting cardiotoxic effects.
      Didox combination with DOX significantly decreased in the IC50 of DOX to half its
      original value in Huh7 and HepG2 liver cancer cell lines. The calculated
      combination index (CI-value) indicated additive type of drug interaction (CI
      value ranged from 0.81 to 0.9). Both didox and DOX significantly blocked the cell
      cycle in S-phase and their combination significantly increased cell cycle
      blockade. Also, didox combination significantly increase the caspase-3 level
      compared to DOX treatment alone. On the other hand, didox (150 mg/kg daily)
      significantly protected the cardiomyocyte membrane integrity and decreased the
      intra-cardiac oxidative stress induced by DOX treatment (15 mg/kg). This
      protective effect was reflected in reverting the cardiomegaly and cardio
      pathological features induced by DOX treatment. Also didox prolonged the median
      survival time of mice treated with DOX and decreased the mortality risk by 3.7
      folds. In conclusion, didox significantly potentiated the cytotoxicity of DOX in
      liver cancer cells and protected from its cardiotoxicity.

PMID- 24021538
TI  - Neuroinflammatory phenotypes and their roles in Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized pathologically by the
      presence of amyloid plaques and neurofibrillary tangles in the brain. While once
      considered immunologically privileged due to the blood-brain barrier, it is now
      understood that the glial cells of the brain are capable of complex inflammatory
      responses. OBJECTIVE: The goal of the study is to assess the neuroinflammatory
      state of the early and late AD brain using the macrophage categorizations of M1,
      M2a, M2b and M2c. METHODS: We used quantitative real-time RT-PCR to assess a
      number of inflammatory markers in the frontal cortex and cerebellar tissue from
      early and late AD patients. We then used neuropathological and clinical outcomes
      to determine whether there were any correlations. RESULTS: We found that the AD
      brain is capable of generating all macrophage-like responses. In addition, we
      found that early AD is distinct from late AD with respect to the inflammatory
      profiles expressed in the brain. Most interestingly, however, we found that the
      early AD samples were biased to one of two phenotypes, M1 or M2a. CONCLUSION:
      Heterogeneity in the neuroinflammatory state of the early AD brain.

PMID- 24021539
TI  - DDT/DDE and breast cancer: a meta-analysis.
AB  - The biological basis for investigating dichlorodiphenyltrichloroethane (DDT)
      exposure and breast cancer risk stems from in vitro and animal studies indicating
      that DDT has estrogenic properties. The objective of this study was to update a
      meta-analysis from 2004 which found no association between
      dichlorodiphenyldichloroethylene (DDE) and breast cancer. We searched PubMed and
      Web of Science for studies published through June 2012 assessing DDT/DDE exposure
      and breast cancer. Summary Odds Ratios (ORs) with 95% confidence intervals (CIs)
      were calculated for the prevalence of breast cancer in the highest versus the
      lowest exposed groups for DDT and DDE. Difference of means of exposure for cases
      versus controls was analyzed for DDT and DDE. From the 500 studies screened, 46
      were included in the meta-analysis. Slightly elevated, but not statistically
      significant summary ORs were found for DDE (1.05; 95% CI: 0.93-1.18) and DDT
      (1.02; 95% CI: 0.92-1.13). Lipid adjusted difference of means analysis found a
      significantly higher DDE concentration in cases versus controls (11.30 ng/g
      lipid; p=0.01). No other difference of means analysis found significant
      relationships. The existing information does not support the hypothesis that
      exposure to DDT/DDE increases the risk of breast cancer in humans.

PMID- 24021540
TI  - Concrete steps toward academic medicine in long term care.

PMID- 24021541
TI  - Phase II trial of gefitinib alone without radiation therapy for Japanese patients
      with brain metastases from EGFR-mutant lung adenocarcinoma.
AB  - BACKGROUND: Brain metastases (BM) are a common in patients with lung cancer.
      Although whole-brain radiation therapy (WBRT) is the standard therapy, it may
      have a risk of decline in cognitive function of patients. In this study, we
      evaluated the efficacy of gefitinib alone without radiation therapy for the
      treatment of patients with BM from lung adenocarcinoma. MATERIALS AND METHODS:
      Eligible patients had BM from lung adenocarcinoma with epidermal growth factor
      receptor (EGFR) mutations. Gefitinib was given at 250 mg orally once a day until
      tumor progression or unacceptable toxicity. RESULTS: Forty-one patients were
      enrolled. The response rate was 87.8%. No patient experienced grade >=4 toxicity.
      The median progression-free survival time was 14.5 months (95% CI, 10.2-18.3
      months), and the median overall survival time was 21.9 months (95% CI, 18.5-30.3
      months). In compared with L858R, exon 19 deletion was associated with better
      outcome of patients after treatment with gefitinib in both progression-free (p =
      0.003) and overall survival (p = 0.025). CONCLUSION: Favorable response of BM to
      gefitinib even without irradiation was demonstrated. Exon 19 deletion was both a
      predictive and prognostic marker of patients with BM treated by gefitinib.

PMID- 24021542
TI  - Effect on performance of weanling alpacas following treatments against gastro
      intestinal parasites.
AB  - Nematodes and coccidia are common parasites of alpacas (Vicugna pacos), and
      important causes of disease in this increasingly popular livestock species.
      Endoparasitic infestation is thought to increase at times of natural or imposed
      stress, and antiparasitic treatments are often administered, although to date
      there is little evidence regarding their effect. Thirty-one alpaca juvenilles
      (cria) were divided into four groups at weaning, and received either no treatment
      as a control (C), fenbendazole anthelmintic (FB), toltrazuril coccidiostat (T),
      or both treatments (FBT). Body weights and faecal egg/oocyst counts were recorded
      weekly for six weeks following treatment. Although the prophylactic treatments
      decreased faecal egg/oocyst counts of the target organisms in the short term,
      there was no significant difference in egg/oocyst output over the course of the
      trial from animals given wormer, coccidiostat or both treatments. The group
      receiving anthelmintic only showed a significant reduction in live weight gain
      (LWG), with no significant difference in LWG between the other groups. At the
      conclusion of the trial, 'wormed only' alpacas weighed 3.3% less than at weaning,
      losing an average 1.3 kg over six weeks, whereas average LWG in the control group
      was 2.5 kg. Antiparasitics transiently reduced egg/oocyst output but results
      suggest that further investigation is required on the action of anthelmintics
      administered to alpaca cria at weaning and their effect on animal health and
      welfare.

PMID- 24021543
TI  - Real time simulation of nonlinear generalized predictive control for wind energy
      conversion system with nonlinear observer.
AB  - In order to make a wind power generation truly cost-effective and reliable, an
      advanced control techniques must be used. In this paper, we develop a new control
      strategy, using nonlinear generalized predictive control (NGPC) approach, for
      DFIG-based wind turbine. The proposed control law is based on two points: NGPC
      based torque-current control loop generating the rotor reference voltage and NGPC
      based speed control loop that provides the torque reference. In order to enhance
      the robustness of the controller, a disturbance observer is designed to estimate
      the aerodynamic torque which is considered as an unknown perturbation. Finally, a
      real-time simulation is carried out to illustrate the performance of the proposed
      controller. 

PMID- 24021544
TI  - Modeling and control approach to a distinctive quadrotor helicopter.
AB  - The referenced quadrotor helicopter in this paper has a unique configuration. It
      is more complex than commonly used quadrotors because of its inaccurate
      parameters, unideal symmetrical structure and unknown nonlinear dynamics. A novel
      method was presented to handle its modeling and control problems in this paper,
      which adopts a MIMO RBF neural nets-based state-dependent ARX (RBF-ARX) model to
      represent its nonlinear dynamics, and then a MIMO RBF-ARX model-based global LQR
      controller is proposed to stabilize the quadrotor's attitude. By comparing with a
      physical model-based LQR controller and an ARX model-set-based gain scheduling
      LQR controller, superiority of the MIMO RBF-ARX model-based control approach was
      confirmed. This successful application verified the validity of the MIMO RBF-ARX
      modeling method to the quadrotor helicopter with complex nonlinearity. 

PMID- 24021545
TI  - Granulomatosis with polyangiitis presenting as a renal mass successfully treated
      with rituximab.

PMID- 24021546
TI  - Uniform tricalcium phosphate beads with an open porous structure for tissue
      engineering.
AB  - Uniform tricalcium phosphate (TCP) porous beads with micro and macro pore sizes
      were fabricated using a simple fluidic device. For micro-porous TCP beads, an
      aqueous gelatin mixture containing TCP powder was introduced as the discontinuous
      phase into the fluidic device, where a toluene phase served as the continuous
      phase. The resulting aqueous TCP droplets were instantly frozen at -20 degrees C
      and freeze-dried, followed by calcination at 1200 degrees C. An oil-in-water-in
      oil (O/W/O) emulsion templating method was employed to fabricate macro-porous TCP
      beads. An oil-in-water (O/W) emulsion was introduced into the fluidic device as
      the discontinuous phase with all other experimental conditions the same as for
      the micro-porous TCP beads. Uniform macro-porous TCP beads with a highly porous
      structure were finally obtained after freeze-drying and calcination. Large pore
      size and good interconnectivity of the macro-porous TCP beads were confirmed by
      scanning electron microscopy and porosimetry. In addition, penetration of host
      tissue into the macro-pores of the TCP beads was demonstrated by subcutaneously
      implanting the two types of porous TCP beads into mice and histologically
      analyzing stained sections at 1-4 weeks post implantation. The macro-porous TCP
      beads with a highly open porous structure could potentially be used as an
      injectable material for bone tissue engineering. 

PMID- 24021547
TI  - Overclock your brain for gaming? Ethical, social and health care risks.

PMID- 24021548
TI  - Ethics and social risks in brain stimulation.

PMID- 24021550
TI  - First birth Caesarean section and subsequent fertility: a population-based study
      in the USA, 2000-2008.
AB  - STUDY QUESTION: Is first birth Caesarean delivery associated with a lower
      likelihood of subsequent childbearing when compared with first birth vaginal
      delivery? SUMMARY ANSWER: In this study of US women whose first delivery was in
      2000, those who had a Caesarean delivery were less likely to have a subsequent
      live birth than those who delivered vaginally. WHAT IS ALREADY KNOWN: Some
      studies have reported lower birth rates subsequent to Caesarean delivery in
      comparison with vaginal delivery, while other studies have reported no
      difference. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective cohort
      study of 52 498 women who had a first singleton live birth in the State of
      Pennsylvania, USA in 2000 and were followed to the end of 2008 via Pennsylvania
      birth certificate records to identify subsequent live births during the 8- to 9
      year follow-up period. PARTICIPANTS/MATERIALS, SETTING, METHODS: Birth
      certificate records of first singleton births were linked to the hospital
      discharge data for each mother and newborn, and linked to all birth certificate
      records for each mother's subsequent deliveries which occurred in 2000 to the end
      of 2008. Poisson regression models were used to evaluate the association between
      first birth factors and whether or not there was a subsequent live birth during
      the follow-up period. MAIN RESULTS AND THE ROLE OF CHANCE: Over an average of 8.5
      years of follow-up, 40.2% of women with a Caesarean first birth did not have a
      subsequent live birth, compared with 33.1% of women with a vaginal first birth
      (risk ratio (RR): 1.21, 95% confidence interval (CI): 1.18-1.25). Adjustment for
      the demographic confounders of maternal age, race, education, marital status and
      health insurance coverage attenuated the RR to 1.16 (95% CI: 1.13-1.19). Specific
      pregnancy and childbirth-related complications associated with not having a
      subsequent live birth included diabetes-related disorders, abnormalities of
      organs and soft tissues of the pelvis, fetal abnormalities, premature or
      prolonged rupture of membranes, hypertensive disorders, amnionitis, fetal
      distress and other maternal health problems. However, adjustment for the
      pregnancy and childbirth complications had little effect on the RR of not having
      a subsequent live birth (RR = 1.15, 95% CI: 1.11-1.19). LIMITATIONS, REASONS FOR
      CAUTION: We were unable to distinguish between women who did not have a
      subsequent live birth and those who moved out of the state, which may have
      introduced a selection bias if those who had Caesarean births were more likely to
      emigrate than those who delivered vaginally. In addition we were unable to
      measure pre-pregnancy body mass index, weight gain during pregnancy and prior
      infertility, which would have been helpful in our efforts to reduce selection
      bias. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study provide
      further corroboration of previous studies that have reported reduced fertility
      subsequent to Caesarean section in comparison with vaginal delivery. STUDY
      FUNDING/POTENTIAL COMPETING INTERESTS: This study was funded by the US National
      Institute of Child Health and Human Development (NICHD, R01-HD052990). No
      competing interests are declared.

PMID- 24021551
TI  - Effect of copy number variants on outcomes for infants with single ventricle
      heart defects.
AB  - BACKGROUND: Human genomes harbor copy number variants (CNVs), which are regions
      of DNA gains or losses. Although pathogenic CNVs are associated with congenital
      heart disease (CHD), their effect on clinical outcomes is unknown. This study
      sought to determine whether pathogenic CNVs among infants with single ventricle
      physiology were associated with inferior neurocognitive and somatic growth
      outcomes. METHODS AND RESULTS: Genomic DNAs from 223 subjects of 2 National
      Heart, Lung, and Blood Institute-sponsored randomized clinical trials in infants
      with single ventricle CHD and 270 controls from The Cancer Genome Atlas project
      were analyzed for rare CNVs>300 kb using array comparative genomic hybridization.
      Neurocognitive and growth outcomes at 14 months from the CHD trials were compared
      among subjects with and without pathogenic CNVs. Putatively pathogenic CNVs,
      comprising 25 duplications and 6 deletions, had a prevalence of 13.9%,
      significantly greater than the 4.4% rate of such CNVs among controls. CNVs
      associated with genomic disorders were found in 13 cases but not in controls.
      Several CNVs likely to be causative of single ventricle CHD were observed,
      including aberrations altering the dosage of GATA4, MYH11, and GJA5. Subjects
      with pathogenic CNVs had worse linear growth, and those with CNVs associated with
      known genomic disorders had the poorest neurocognitive and growth outcomes. A
      minority of children with pathogenic CNVs were noted to be dysmorphic on clinical
      genetics examination. CONCLUSIONS: Pathogenic CNVs seem to contribute to the
      cause of single ventricle forms of CHD in >=10% of cases and are clinically
      subtle but adversely affect outcomes in children harboring them.

PMID- 24021552
TI  - The role of CAV3 in long-QT syndrome: clinical and functional assessment of a
      caveolin-3/Kv11.1 double heterozygote versus caveolin-3 single heterozygote.
AB  - BACKGROUND: Mutations in CAV3, coding for caveolin-3, the major constituent
      scaffolding protein of cardiac caveolae, have been associated with skeletal
      muscle disease, cardiomyopathy, and most recently long-QT syndrome (LQTS) and
      sudden infant death syndrome. We examined the occurrence of CAV3 mutations in a
      large cohort of patients with LQTS. METHODS AND RESULTS: Probands with LQTS
      (n=167) were screened for mutations in CAV3 using direct DNA sequencing. A single
      proband (0.6%) was found to be a heterozygous carrier of a previously described
      missense mutation, caveolin-3:p.T78M. The proband was also a heterozygous carrier
      of the trafficking-deficient Kv11.1:p.I400N mutation. The caveolin-3:p.T78M
      mutation was found isolated in 3 family members, none of whom had a prolonged QTc
      interval. Coimmunoprecipitations of caveolin-3 and the voltage-gated potassium
      channel subunit (Kv11.1) were performed, and the electrophysiological
      classification of the Kv11.1 mutant was carried out by patch-clamp technique in
      human embryonic kidney 293 cells. Furthermore, the T-wave morphology was assessed
      in mutation carriers, double mutation carriers, and nonmutation carriers by
      applying a morphology combination score. The morphology combination score was
      normal for isolated caveolin-3:p.T78M carriers and of LQT2 type in double
      heterozygotes. CONCLUSIONS: Mutations in CAV3 are rare in LQTS. Furthermore,
      caveolin-3:p.T78M did not exhibit a LQTS phenotype. Because no association has
      ever been found between LQTS and isolated CAV3 mutations, we suggest that LQTS9
      is considered a provisional entity.

PMID- 24021553
TI  - Postreplication targeting of transformants by bacterial immune systems?
AB  - Bacteria are constantly challenged by foreign genetic elements such as
      bacteriophages and plasmids. Several defense systems provide immunity against
      such attackers, including restriction-modification (R-M) systems and clustered,
      regularly interspaced short palindromic repeats (CRISPRs). These systems target
      attacking DNA and thus antagonize natural transformation, which relies on uptake
      of exogenous DNA to promote acquisition of new genetic traits. It is unclear how
      this antagonization occurs, because transforming DNA is single stranded, and thus
      resistant to these immune systems. Here, we propose a simple model whereby these
      systems limit transformation by attack of transformed chromosomes once double
      strandedness is restored by chromosomal replication. 

PMID- 24021554
TI  - Clinical features and treatment outcomes of intravascular large B-cell lymphoma:
      a single-center experience in Korea.
AB  - BACKGROUND: Clinical features and treatment outcomes of intravascular large B
      cell lymphoma (IVLBCL) have rarely been reviewed due to its rarity and pathologic
      obscurity. METHODS: We analyzed 20 patients who were pathologically diagnosed
      with IVLBCL at the Samsung Medical Center. RESULTS: Initial manifestations were
      nonspecific, such as fever with cytopenia, elevated serum lactate dehydrogenase
      and hypoalbuminemia. Hemophagocytosis was frequent and bone marrow was the most
      common site of pathologic diagnosis in our series. Hepatosplenomegaly, pleural
      effusion and ground-glass opacity in the lungs were also commonly found, and
      positron emission tomography imaging showed increased (18)F-fluorodeoxyglucose
      uptake in the involved organs. All patients received CHOP (cyclophosphamide,
      doxorubicin, vincristine and prednisone) or rituximab-CHOP. The median overall
      survival (OS) was 38.9 months (95% confidence interval 6.7-71.1). Rituximab
      containing chemotherapy compared to chemotherapy alone resulted in higher 3-year
      OS (71.4 and 25.0%; p = 0.027). Patients with hemophagocytosis had a poorer 3
      year OS compared to patients without hemophagocytosis (29.6 and 75%; p = 0.046).
      Prognostic factor analysis showed the association of pleural effusion with worse
      OS (p = 0.002). CONCLUSIONS: Treatment with rituximab-containing chemotherapy can
      improve the treatment outcome of IVLBCL. Pleural effusion may be a poor
      prognostic factor in patients with IVLBCL.

PMID- 24021555
TI  - Orchidectomy after primary chemotherapy for metastatic testicular cancer.
AB  - OBJECTIVE: To examine the outcome of orchidectomy following primary chemotherapy
      in patients with metastatic testicular cancer. PATIENTS AND METHODS: This was a
      retrospective analysis of patients who underwent primary chemotherapy without
      initial orchidectomy for testicular cancer between 1982 and 2006. The patients
      were identified from the regional oncology cancer database in our tertiary
      referral hospital. Their case notes were reviewed regarding initial presentation,
      chemotherapy, clinical progress and pathological outcomes following surgery.
      RESULTS: 21 evaluable patients were identified (14 non-seminomatous germ cell
      tumours, 7 seminomas). 16 patients underwent standard orchidectomy within 12
      months of commencing chemotherapy and 5 patients underwent significantly delayed
      orchidectomy (19-68 months, mean 45.1 months). Orchidectomy in the standard group
      showed tumour necrosis or a scar in 13 patients (81%) and differentiated or
      mature teratoma in 3 patients associated with bulky poorly responsive
      retroperitoneal disease (19%). In the delayed orchidectomy group 3 out of 5
      patients had viable seminoma, of which two were associated with carcinoma in
      situ. CONCLUSION: Our study raises concerns as regards a potentially high risk of
      late tumour development in testes which are preserved following apparent tumour
      resolution after chemotherapy.

PMID- 24021556
TI  - Thymofibrolipoma in a labrador retriever.
AB  - While thymomas are uncommon but well-known mediastinal masses, collagen-rich
      variants are exceedingly rare. Thymofibrolipoma and sclerosing thymoma tumor
      variants have been recently recognized in medical pathology, and thymofibrolipoma
      has been only rarely reported in dogs. A cranial thoracic mass was identified in
      a 6-year-old Labrador Retriever that was characterized by robust collagenous
      stroma dissected by thin cords of cytokeratin-positive neoplastic epithelial
      cells and bordered by mildly pleomorphic epithelial cells with occasional
      lymphocytic aggregates and rare Hassall corpuscles. To the authors' knowledge,
      this is only the second report of thymofibrolipoma in veterinary medicine and the
      first to describe a variant with a mitotically active and relatively pleomorphic,
      adjacent thymic epithelial population. 

PMID- 24021557
TI  - Failure of respiratory defenses in the pathogenesis of bacterial pneumonia of
      cattle.
AB  - The respiratory system is well defended against inhaled bacteria by a dynamic
      system of interacting layers, including mucociliary clearance, host defense
      factors including antimicrobial peptides in the epithelial lining fluid,
      proinflammatory responses of the respiratory epithelium, resident alveolar
      macrophages, and recruited neutrophils and monocytes. Nevertheless, these
      manifold defenses are susceptible to failure as a result of stress,
      glucocorticoids, viral infections, abrupt exposure to cold air, and poor air
      quality. When some of these defenses fail, the lung can be colonized by bacterial
      pathogens that are equipped to evade the remaining defenses, resulting in the
      development of pneumonia. This review considers the mechanisms by which these
      predisposing factors compromise the defenses of the lung, with a focus on the
      development of bacterial pneumonia in cattle and supplemented with advances based
      on mouse models and the study of human disease. Deepening our understanding of
      how the respiratory defenses fail is expected to lead to interventions that
      restore these dynamic immune responses and prevent disease. 

PMID- 24021558
TI  - Superficial necrolytic dermatitis in a dog with an insulin-producing pancreatic
      islet cell carcinoma.
AB  - A 10-year-old dog presented with convulsive crisis and symmetrical hyperkeratotic
      cutaneous lesions affecting the abdomen, inguinal area, eyelids, muzzles, both
      pinnae, and all the paw pads. Hypoglycemia and hyperinsulinemia were the main
      biochemical findings. A mass 2 cm in diameter was detected within the left
      pancreatic lobe by ultrasonography. It was surgically removed and histologically
      and immunohistochemically diagnosed as an insulin-producing pancreatic islet cell
      carcinoma. The animal was eventually euthanized due to lack of clinical
      improvement. At necropsy, metastatic nodules were observed in the pancreatic
      lymph nodes and liver. Histopathological findings of cutaneous lesions were
      highly suggestive of superficial necrolytic dermatitis and were interpreted as a
      paraneoplastic syndrome derived from the islet cell carcinoma. To the authors'
      knowledge, this is the first report of superficial necrolytic dermatitis
      associated with an insulin-producing pancreatic neuroendocrine carcinoma in dogs.

PMID- 24021559
TI  - Malakoplakia with digestive tract involvement in a pig.
AB  - Malakoplakia is a rare, granulomatous, inflammatory disease that mimics malignant
      tumors and can affect any organ. Herein is described a case of malakoplakia in a
      10-month-old slaughter pig. Diffuse, pleomorphic, round cell infiltrates, mainly
      histiocytes, with a tumor-like growth pattern at gross examination, infiltrated
      the stomach, pancreas, omentum, and mesenteric lymph nodes. The histiocytes and
      multinucleated giant cells had concentric, target-like inclusions known as
      Michaelis-Gutmann bodies. Microorganisms were not detected by the periodic acid
      Schiff reaction, Ziehl-Neelsen, Gram, and Warthin-Starry staining or by electron
      microscopic and bacteriologic investigations. Porcine circovirus type 2 and
      porcine reproductive and respiratory syndrome viruses were not detected by
      immunohistochemistry in the sections examined. 

PMID- 24021560
TI  - Recent trends in HIV-1 drug resistance.
AB  - Once considered an inevitable consequence of HIV treatment, drug resistance is
      declining. This decline supports the hypothesis that antiretroviral therapy can
      arrest replication and prevent the evolution of resistance. Further support comes
      from excellent clinical outcomes, the failure of treatment intensification to
      reduce residual viremia, the lack of viral evolution in patients on optimal
      therapy, pharmacodynamics studies explaining the extraordinarily high antiviral
      activity of modern regimens, and recent reports of potential cures. Evidence
      supporting ongoing replication includes higher rates of certain complications in
      treated patients and an increase in circular forms of the viral genome after
      intensification with integrase inhibitors. Recent studies also provide an
      explanation for the observation that some patients fail protease-inhibitor based
      regimens without evidence for resistance. 

PMID- 24021561
TI  - Brain protein expression changes in WAG/Rij rats, a genetic rat model of absence
      epilepsy after peripheral lipopolysaccharide treatment.
AB  - Peripheral injection of bacterial lipopolysaccharide (LPS) facilitates 8-10Hz
      spike-wave discharges (SWD) characterizing absence epilepsy in WAG/Rij rats. It
      is unknown however, whether peripherally administered LPS is able to alter the
      generator areas of epileptic activity at the molecular level. We injected 1mg/kg
      dose of LPS intraperitoneally into WAG/Rij rats, recorded the body temperature
      and EEG, and examined the protein expression changes of the proteome 12h after
      injection in the fronto-parietal cortex and thalamus. We used fluorescent two
      dimensional differential gel electrophoresis to investigate the expression
      profile. We found 16 differentially expressed proteins in the fronto-parietal
      cortex and 35 proteins in the thalamus. It is known that SWD genesis correlates
      with the transitional state of sleep-wake cycle thus we performed meta-analysis
      of the altered proteins in relation to inflammation, epilepsy as well as sleep.
      The analysis revealed that all categories are highly represented by the altered
      proteins and these protein-sets have considerable overlap. Protein network
      modeling suggested that the alterations in the proteome were largely induced by
      the immune response, which invokes the NFkB signaling pathway. The proteomics and
      computational analysis verified the known functional interplay between
      inflammation, epilepsy and sleep and highlighted proteins that are involved in
      their common synaptic mechanisms. Our physiological findings support the
      phenomenon that high dose of peripheral LPS injection increases SWD-number,
      modifies its duration as well as the sleep-wake stages and decreases body
      temperature. 

PMID- 24021562
TI  - Acupuncture applied as a sensory discrimination training tool decreases movement
      related pain in patients with chronic low back pain more than acupuncture alone:
      a randomised cross-over experiment.
AB  - BACKGROUND: High-quality clinical evidence suggests that although acupuncture
      appears superior to usual care in the management of chronic low back pain, there
      is little meaningful difference between true and sham acupuncture. This suggests
      that the benefits of acupuncture are mediated by the placebo response. An
      alternative explanation is that sham acupuncture is an active treatment and
      shares a mechanism of action with traditionally applied acupuncture. One
      plausible candidate for this mechanism is improvement in self-perception mediated
      through the sensory discrimination-like qualities of acupuncture. We aimed to
      compare the effects of acupuncture with a sensory discrimination training
      component to acupuncture without. METHODS: 25 people with chronic low back pain
      were enroled in a randomised cross-over experiment. We compared the effect of
      acupuncture delivered when sensory discrimination is optimised to acupuncture
      delivered when it is not, on movement-related back pain immediately after each
      intervention. RESULTS: We found that the average pain intensity after
      participants had received acupuncture with sensory discrimination training (2.8+/
      2.5) was less than when they received acupuncture without sensory discrimination
      training (3.6+/-2.0). This difference was statistically significant (after
      adjustment; mean difference=-0.8, 95% CI -1.4 to -0.3; p=0.011). CONCLUSIONS: Our
      findings are consistent with the idea that acupuncture may offer specific benefit
      that is not dependent on precisely where the needles are inserted so much as that
      the patient attends to where they are inserted. If so, the location of the
      needles might be better focused on the painful area and the need for penetration
      of the skin may be mitigated.

PMID- 24021563
TI  - Swept-source anterior segment optical coherence tomography in late-onset capsular
      block syndrome: high-resolution imaging and morphometric modifications after
      posterior capsulotomy.
AB  - PURPOSE: To study the characteristics of late-onset capsular block syndrome (CBS)
      using swept-source anterior segment optical coherence tomography (AS-OCT) and
      assess morphometric variations after treatment with neodymium:YAG (Nd:YAG) laser
      posterior capsulotomy. SETTING: Ophthalmology, University of Parma, Parma, Italy.
      DESIGN: Case series. METHODS: Patients with late-onset CBS had an ophthalmology
      evaluation, including slitlamp photography and AS-OCT, before and 1 month after
      ND:YAG laser posterior capsulotomy. The diameter of the anterior capsulorhexis,
      the posterior displacement of the posterior capsule, and the anterior chamber
      depth (ACD) were measured using AS-OCT. Measurements before and after Nd:YAG
      laser posterior capsulotomy were compared using the paired t test. RESULTS: The
      study evaluated 6 patients. Slitlamp examination showed accumulation between the
      intraocular lens (IOL) and the posterior capsule of milky-white or particulate
      liquefied material that appeared hyperreflective on AS-OCT and caused posterior
      displacement of the posterior capsule (mean 1.38 mm). The diameter of the
      anterior capsulorhexis (mean 4.5 mm) was smaller than the IOL optic in all cases.
      After uneventful Nd:YAG laser posterior capsulotomy, the corrected distance
      visual acuity improved in all patients (P<.01). The ACD (IOL position) and
      refraction did not change significantly after the capsulotomy (P=.15 and P=.36,
      respectively). CONCLUSIONS: Anterior segment OCT allowed accurate imaging and
      measurement of anterior segment parameters in late-onset CBS. No displacement of
      the IOL was found after treatment with Nd:YAG laser posterior capsulotomy.
      Neodymium:YAG laser posterior capsulotomy was an effective and safe therapy in
      the 6 late-onset CBS cases.

PMID- 24021564
TI  - Surgical management of malignant glaucoma with white cataract in nanophthalmos.
AB  - We present a 49-year-old woman with nanophthalmos, white cataract, and malignant
      glaucoma in her left eye. The corrected distance visual acuity (CDVA) in that eye
      was hand motion, and the intraocular pressure (IOP) fluctuated between 28 mm Hg
      and 45 mm Hg with antiglaucoma medications. An unsutured sclerectomy combined
      with zonulectomy, hyaloidectomy, and anterior vitrectomy was performed. At 6
      months postoperatively, the IOP was maintained at 12 mm Hg, the anterior chamber
      was deep, and the Snellen CDVA was 20/80. No intraoperative or postoperative
      complications were observed. The outcome in this case suggests that sclerectomy
      combined with phacoemulsification, zonulectomy, hyaloidectomy, and anterior
      vitrectomy is effective for the management of nanophthalmic patients with white
      cataract and malignant glaucoma.

PMID- 24021565
TI  - Combined hydrogel inlay and laser in situ keratomileusis to compensate for
      presbyopia in hyperopic patients: one-year safety and efficacy.
AB  - PURPOSE: To perform a feasibility study of the safety and efficacy of a corneal
      contouring inlay with concurrent laser in situ keratomileusis (LASIK) to treat
      hyperopic presbyopia. SETTING: Private clinic, Tijuana, Mexico. DESIGN:
      Prospective interventional case series. METHODS: Hyperopic patients received
      LASIK in both eyes and a corneal inlay under the femtosecond laser flap in the
      nondominant eye. The inlay is designed to reshape the anterior corneal curvature,
      creating a near-center multifocal refractive effect. Main safety outcomes were
      retention of preoperative corrected distance and near visual acuities and reports
      of adverse events. Efficacy was determined through measurements of near,
      intermediate, and distance visual acuities and patient questionnaires on visual
      task ability and satisfaction. RESULTS: The study enrolled 16 patients. All eyes
      with an inlay achieved an uncorrected near visual acuity (UNVA) of 20/32 or
      better by the 1-week postoperative examination and at every visit thereafter. The
      mean monocular and binocular UNVA was 20/27 or better at all visits. The mean
      binocular uncorrected distance visual acuity improved significantly from 20/53
      preoperatively to 20/19 postoperatively (P<10(-5)). One inlay was explanted
      during the study. At 1 year, all 14 patients analyzed were satisfied or very
      satisfied with their near, distance, and overall vision. CONCLUSIONS: The
      hydrogel corneal inlay with concurrent LASIK improved uncorrected near,
      intermediate, and distance visual acuity in hyperopic presbyopic patients with
      high patient satisfaction and visual task ability. This represents a new
      indication for this recently developed technology.

PMID- 24021567
TI  - Phagocytosis of a mature schizont in severe falciparum malaria.

PMID- 24021566
TI  - The emergence of OXA-48- and NDM-1-positive Klebsiella pneumoniae in Riyadh,
      Saudi Arabia.
AB  - OBJECTIVES: To investigate the emergence of NDM-, OXA-48-, and VIM-producing
      Klebsiella pneumoniae in Saudi Arabia. METHODS: From June to December 2011, we
      obtained K. pneumoniae isolates with reduced sensitivity to carbapenem identified
      in Riyadh, Saudi Arabia. Only non-duplicate clinical and surveillance isolates
      obtained from inpatients were included. PCR amplification was carried out for the
      detection of extended-spectrum beta-lactamase genes (blaCTX-M, blaTEM, blaSHV)
      and carbapenemase genes (blaKPC, blaVIM, blaIMP, blaNDM, and blaOXA-48).
      Susceptibility to imipenem, meropenem, amikacin, gentamicin, trimethoprim
      sulfamethoxazole, and colistin was determined. RESULTS: Of the 60K. pneumoniae
      isolates studied, 45 were from patients in the intensive care unit. Forty-seven
      isolates harbored blaOXA-48, 12 were positive for blaNDM, and one for blaVIM. No
      isolate harbored a combination of these resistance genes. No isolate harbored
      blaKPC or blaIMP. All 37 blaCTX-M-positive isolates belonged to CTX-M group 1,
      and 29 were positive for a combination of blaCTX-M and blaOXA-48. blaTEM and
      blaSHV genes were found in 17 and 39 isolates, respectively. All isolates were
      imipenem- and meropenem-resistant, with a high rate of co-resistance to the other
      antibiotics. Three blaOXA-48-positive isolates with colistin resistance were
      detected. CONCLUSION: Multidrug-resistant K. pneumoniae isolates harboring blaOXA
      48, blaNDM, and colistin resistance are emerging in Saudi Arabia.

PMID- 24021568
TI  - Endocrine problems in children and adolescents who have disabilities.
AB  - The consequences of disability span almost all aspects of life, for families and
      for an affected individual. Endocrine aspects of disability cover disorders of
      hypothalamic pituitary dysfunction, bone health, puberty, fertility, sexual
      function and contraceptive needs. Adequate endocrine assessment for a child with
      a disability requires extensive and sensitive history to address social issues,
      general nutrition, vitamin D status, specific hypothalamic pituitary problems,
      together with parental concerns regarding puberty and contraception. Bone health
      assessment includes history of minimal trauma fracture, need for intervention or
      fitness for surgery. Strategic interventions to improve outcome include
      management of puberty, vitamin D status, biomechanical stimulation with vibration
      and standing and possible consideration for bisphosphonate in special
      circumstances. Both early and late puberty cause major family concerns. The
      paediatrician must be aware of a range of management options to improve outcomes
      for the child and family.

PMID- 24021569
TI  - Protective properties of tanshinone I against oxidative DNA damage and
      cytotoxicity.
AB  - Tanshinone I, a naturally occurring diterpene from Danshen, has been shown to
      possess hepatocyte protective, anticancer, and memory enhancing properties.
      However, there are few stringent pharmacological tests for neuroprotection of
      tanshinone I thus far. Since peroxynitrite is involved in the pathogenesis of
      neurodegenerative disorders, this study was undertaken to investigate whether the
      neuroprotective effect of tanshinone I is associated with inhibition of
      peroxynitrite-caused DNA damage, a critical event leading to peroxynitrite
      induced cytotoxicity. Our results show that tanshinone I can significantly
      inhibit peroxynitrite-induced DNA damage both in phiX-174 plasmid DNA and rat
      primary astrocytes. EPR spectroscopy indicates that tanshinone I potently
      diminished the DMPO-hydroxyl radical adduct signal from peroxynitrite. Taken
      together, these results demonstrate for the first time that tanshinone I can
      protect against peroxynitrite-induced DNA damage, hydroxyl radical formation and
      cytotoxicity, which might have implications for tanshinone I-mediated
      neuroprotection. 

PMID- 24021571
TI  - CHIR99021 promotes self-renewal of mouse embryonic stem cells by modulation of
      protein-encoding gene and long intergenic non-coding RNA expression.
AB  - Embryonic stem cells (ESCs) can proliferate indefinitely in vitro and
      differentiate into cells of all three germ layers. These unique properties make
      them exceptionally valuable for drug discovery and regenerative medicine.
      However, the practical application of ESCs is limited because it is difficult to
      derive and culture ESCs. It has been demonstrated that CHIR99021 (CHIR) promotes
      self-renewal and enhances the derivation efficiency of mouse (m)ESCs. However,
      the downstream targets of CHIR are not fully understood. In this study, we
      identified CHIR-regulated genes in mESCs using microarray analysis. Our
      microarray data demonstrated that CHIR not only influenced the Wnt/beta-catenin
      pathway by stabilizing beta-catenin, but also modulated several other
      pluripotency-related signaling pathways such as TGF-beta, Notch and MAPK
      signaling pathways. More detailed analysis demonstrated that CHIR inhibited Nodal
      signaling, while activating bone morphogenetic protein signaling in mESCs. In
      addition, we found that pluripotency-maintaining transcription factors were up
      regulated by CHIR, while several developmental-related genes were down-regulated.
      Furthermore, we found that CHIR altered the expression of epigenetic regulatory
      genes and long intergenic non-coding RNAs. Quantitative real-time PCR results
      were consistent with microarray data, suggesting that CHIR alters the expression
      pattern of protein-encoding genes (especially transcription factors), epigenetic
      regulatory genes and non-coding RNAs to establish a relatively stable
      pluripotency-maintaining network.

PMID- 24021570
TI  - Polyphenols isolated from Allium cepa L. induces apoptosis by suppressing IAP-1
      through inhibiting PI3K/Akt signaling pathways in human leukemic cells.
AB  - Allium cepa Linn is commonly used as supplementary folk remedy for cancer
      therapy. Evidence suggests that Allium extracts have anti-cancer properties.
      However, the mechanisms of the anti-cancer activity of A. cepa Linn are not fully
      elucidated in human cancer cells. In this study, we investigated anti-cancer
      effects of polyphenols extracted from lyophilized A. cepa Linn (PEAL) in human
      leukemia cells and their mechanisms. PEAL inhibited cancer cell growth by
      inducing caspase-dependent apoptosis. The apoptosis was suppressed by caspase 8
      and 9 inhibitors. PEAL also up-regulated TNF-related apoptosis-inducing ligand
      (TRAIL) receptor DR5 and down-regulated survivin and cellular inhibitor of
      apoptosis 1 (cIAP-1). We confirmed these findings in other leukemic cells (THP-1,
      K562 cells). In addition, PEAL suppressed Akt activity and the PEAL-induced
      apoptosis was significantly attenuated in Akt-overexpressing U937 cells. In
      conclusion, our data suggested that PEAL induced caspase-dependent apoptosis in
      several human leukemic cells including U937 cells. The apoptosis was triggered
      through extrinsic pathway by up-regulating DR5 modulating as well as through
      intrinsic pathway by modulating IAP family members. In addition, PEAL induces
      caspase-dependent apoptosis at least in part through the inhibition of
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. This study provides
      evidence that PEAL might be useful for the treatment of leukemia. 

PMID- 24021573
TI  - Reply: To PMID 23639306.

PMID- 24021572
TI  - Sphingosine-1-phosphate receptor 2 protects against anaphylactic shock through
      suppression of endothelial nitric oxide synthase in mice.
AB  - BACKGROUND: Sphingosine-1-phosphate receptor 2 (S1P(2)) is expressed in vascular
      endothelial cells (ECs). However, the role of S1P(2) in vascular barrier
      integrity and anaphylaxis is not well understood. Endothelial nitric oxide
      synthase (eNOS) generates nitric oxide to mediate vascular leakage, compromising
      survival in patients with anaphylaxis. We recently observed that endothelial
      S1P(2) inhibits Akt, an activating kinase of eNOS. OBJECTIVE: We tested the
      hypothesis that endothelial S1P(2) might suppress eNOS, exerting a protective
      effect against endothelial barrier disruption and anaphylaxis. METHODS: Mice
      deficient in S1P(2) and eNOS underwent antigen challenge or platelet-activating
      factor (PAF) injection. Analyses were performed to examine vascular permeability
      and the underlying mechanisms. RESULTS: S1pr2 deletion augmented vascular leakage
      and lethality after either antigen challenge or PAF injection. PAF injection
      induced activation of Akt and eNOS in the aortas and lungs of S1pr2-null mice,
      which were augmented compared with values seen in wild-type mice. Consistently,
      PAF-induced increase in cyclic guanosine monophosphate levels in the aorta was
      enhanced in S1pr-null mice. Genetic Nos3 deletion or pharmacologic eNOS blockade
      protected S1pr2-null mice from aggravation of barrier disruption after antigen
      challenge and PAF injection. ECs isolated from S1pr2-null mice exhibited greater
      stimulation of Akt and eNOS, with enhanced nitric oxide production in response to
      sphingosine-1-phosphate or PAF, compared with that seen in wild-type ECs.
      Moreover, S1pr2-deficient ECs showed more severe disassembly of adherens
      junctions with augmented S-nitrosylation of beta-catenin in response to PAF,
      which was restored by pharmacologic eNOS blockade. CONCLUSION: S1P(2) diminishes
      harmful robust eNOS stimulation and thereby attenuates vascular barrier
      disruption, suggesting potential usefulness of S1P(2) agonists as novel
      therapeutic agents for anaphylaxis.

PMID- 24021574
TI  - Suppression of allergen-specific B lymphocytes by chimeric protein-engineered
      antibodies.
AB  - House dust mites Dermatophagoides pteronyssinus (Dpt) are among the most frequent
      causes of allergy symptoms in Europe. Der p 1 is one of the major allergenic
      compounds of Dpt and the pathological Der p 1-specific B cells play a key role as
      producers of allergen-binding antibodies. The selective elimination of these
      cells by artificial protein molecules which inhibit the production of Dpt
      recognizing IgE antibodies is a perspective therapeutic goal of allergy. A
      protein engineered chimeric molecule has been constructed, which binds Der p 1
      specific B cells via their BCR and suppresses selectively the production of anti
      Der p 1 antibodies via CR1. The synthetic peptide Der p 1 p52-71 and an anti-CD35
      monoclonal antibody were used for the construction of Der p 1 chimera. The
      functional effects of engineered antibodies were analyzed in vitro using PBMCs
      from allergy patients. Significant inhibition of allergen-specific proliferation
      and reduction of Der p 1-IgE antibody production were observed after treatment of
      PBMCs from allergic patients with Der p 1-peptide chimera. Culturing of these
      PBMCs in the presence of the chimeric molecule increased the percentage of
      apoptotic (Annexin V-positive) B lymphocytes, but not T lymphocytes. 

PMID- 24021575
TI  - Valproate prevents dysregulation of spinal glutamate and reduces the development
      of hypersensitivity in rats after peripheral nerve injury.
AB  - The present study examined whether the histone deacetylase inhibitor valproate
      prevents downregulation of glutamate transporters in the primary cultured
      astrocytes and in the spinal cord after L5-L6 spinal nerve ligation (SNL) and
      whether this action of valproate on spinal glutamate transporters prevents spinal
      glutamate dysregulation and development of hypersensitivity after SNL. In
      cultured astrocytes, valproate prevented downregulation of glutamate transporter
      1 (GLT-1) and glutamate-aspartate transporter in a concentration-dependent
      manner. Repeated oral administration of valproate reduced the development of
      hypersensitivity and prevented the downregulation of spinal GLT-1 and glutamate
      aspartate transporter expression in rats after SNL, but did not affect mechanical
      nociception and expression of those transporters in normal rats. Valproate's
      effects on hypersensitivity and spinal GLT-1 expression in SNL rats were blocked
      by intrathecal administration of the selective GLT-1 blocker dihydrokainic acid
      or the GLT-1 selective small interfering RNA (siRNA). Extracellular glutamate
      concentration in the spinal cord, measured by microdialysis, was increased in
      animals with SNL or after GLT-1 selective siRNA treatment, and valproate
      prevented the SNL-induced glutamate increase. These results suggest that
      valproate reduces the development of chronic pain after nerve injury in part by
      preventing downregulation of glutamate transporters, especially GLT-1, to
      maintain normal extracellular glutamate concentrations in the spinal cord.
      PERSPECTIVE: This study demonstrates that valproate prevents the downregulation
      of glutamate transporters in the spinal cord, which contributes in part to the
      development of chronic pain after nerve injury. Given clinical availability and
      established safety profiles, perioperative use of valproate should be tested to
      prevent chronic pain after surgery.

PMID- 24021576
TI  - Reports of chronic pain in childhood and adolescence among patients at a tertiary
      care pain clinic.
AB  - Although chronic pain in childhood can last into adulthood, few studies have
      evaluated the characteristics of adults with chronic pain who report childhood
      chronic pain. Thus, 1,045 new patients (mean age, 49.5 +/- 15.4) at an academic
      tertiary care pain clinic were prospectively evaluated using validated self
      report questionnaires. Patients also responded to questions about childhood pain.
      We found that almost 17% (n = 176) of adult chronic pain patients reported a
      history of chronic pain in childhood or adolescence, with close to 80% indicating
      that the pain in childhood continues today. Adults reporting childhood chronic
      pain were predominantly female (68%), commonly reported widespread pain (85%),
      and had almost 3 times the odds of meeting survey criteria for fibromyalgia (odds
      ratio [OR] = 2.94, 95% confidence interval [CI] = 2.04-4.23) than those denying
      childhood chronic pain. Similarly, those with childhood pain had twice the odds
      of having biological relatives with chronic pain (OR = 2.03, 95% CI = 1.39-2.96)
      and almost 3 times the odds of having relatives with psychiatric illness (OR =
      2.85, 95% CI = 1.97-4.11). Lastly, compared to patients who did not report
      childhood chronic pain, those who did were more likely to use neuropathic
      descriptors for their pain (OR = 1.82, 95% CI = 1.26-2.64), have slightly worse
      functional status (B = -2.12, t = -3.10, P = .002), and have increased anxiety
      (OR = 1.77, 95% CI = 1.24-2.52). PERSPECTIVE: Our study revealed that 1 in 6
      adult pain patients reported pain that dated back to childhood or adolescence. In
      such patients, evidence suggested that their pain was more likely to be
      widespread, neuropathic in nature, and accompanied by psychological comorbidities
      and decreased functional status.

PMID- 24021577
TI  - Patients' perception of postoperative pain management: validation of the
      International Pain Outcomes (IPO) questionnaire.
AB  - PAIN OUT is a European Commission-funded project aiming at improving
      postoperative pain management. It combines a registry that can be useful for
      quality improvement and research using treatment and patient-reported outcome
      measures. The core of the project is a patient questionnaire-the International
      Pain Outcomes questionnaire-that comprises key patient-level outcomes of
      postoperative pain management, including pain intensity, physical and emotional
      functional interference, side effects, and perceptions of care. Its psychometric
      quality after translation and adaptation to European patients is the subject of
      this validation study. The questionnaire was administered to 9,727 patients in 10
      languages in 8 European countries and Israel. Construct validity was assessed
      using factor analysis. Discriminant validity assessment used Mann-Whitney U tests
      to detect mean group differences between 2 surgical disciplines. Internal
      consistency reliability was calculated as Cronbach's alpha. Factor analysis
      resulted in a 3-factor structure explaining 53.6% of variance. Cronbach's alpha
      at overall scale level was high (.86), and for the 3 subscales was low, moderate,
      or high (range, .53-.89). Significant mean group differences between general and
      orthopedic surgery patients confirmed discriminant validity. The psychometric
      quality of the International Pain Outcomes questionnaire can be regarded as
      satisfactory. PERSPECTIVE: The International Pain Outcomes questionnaire provides
      an instrument for postoperative pain assessment and improvement of quality of
      care, which demonstrated good psychometric quality when translated into a variety
      of languages in a large European and Israeli patient population. This measure
      provides the basis for the first comprehensive postoperative pain registry in
      Europe and other countries.

PMID- 24021579
TI  - Re: Should we give vitamin D to severe burns patients? The conundrum.

PMID- 24021578
TI  - Mechanical pain sensitivity and the severity of chronic neck pain and disability
      are not modulated across the menstrual cycle.
AB  - Despite the high prevalence of neck pain among women, menstrual effects on
      regional pain outcomes have not been investigated in this clinical population.
      This study evaluated menstrual effects on mechanical pain sensitivity (pressure
      pain threshold [PPT]), neck pain intensity (numeric pain rating scale [NPRS]),
      and neck-related disability (Neck Disability Index [NDI]) in 22 normally
      menstruating (NM) and 17 hormonal contraceptive users with chronic neck pain. Sex
      hormones, PPT, and NDI were measured during the early follicular (F1), late
      follicular (F2), and luteal (L) menstrual phases. Daily NPRS scores were recorded
      in an online symptom diary and averaged within each phase. Estradiol and
      progesterone increased only for NM women in F2 and L, respectively. Phase effects
      on PPT (eta(2) = .003), NDI (eta(2) = .003), and NPRS (eta(2) = .016) for NM
      women were small and did not differ from those for the hormonal contraceptive
      users (P >= .386). Averaged across the menstrual cycle, PPT scores explained 29%
      of the variance in NPRS scores for NM women but were not associated with NDI
      scores in either group. Results indicate that the magnitude of menstrual effects
      on mechanical pain sensitivity and the severity of neck pain and disability do
      not exceed thresholds of clinically detectable change in women with chronic neck
      pain. PERSPECTIVE: Fluctuations in evoked and clinical pain outcomes across the
      menstrual cycle do not appear to be of sufficient magnitude to impact clinical
      decision making for women with chronic neck pain.

PMID- 24021580
TI  - Non-radiographic axial spondyloarthritis: what is it?
AB  - The classification criteria recently developed by the Assessment of
      Spondyloarthritis International Society (ASAS) highlighted a specific entity: non
      radiographic axial spondyloarthritis (nr-axSpA). Although more and more widely
      used in the literature as well as clinical trials, limits and profile of this
      entity is still under known or debated. Some studies have already compared those
      forms to classical AS, even in recent forms. They showed that, apart from the
      difference in the ossification process, and the greater degree and frequency of
      systemic and MRI inflammation in AS, those 2 forms of SpA share the same genetic
      background, clinical patterns, and burden of disease. TNF antagonists seemed as
      effective in controlling symptoms in patients with nr-axSpA. Concerning the long
      term outcome of nr-ax-SpA, only long-term ongoing cohorts of patients with recent
      nr-axSpA will be able to determine what proportion of patients have persistent
      non-radiographic disease and what proportion do progress to AS. 

PMID- 24021581
TI  - Selective inhibition of heme oxygenase-2 activity by analogs of 1-(4
      chlorobenzyl)-2-(pyrrolidin-1-ylmethyl)-1H-benzimidazole (clemizole): Exploration
      of the effects of substituents at the N-1 position.
AB  - Several analogs based on the lead structure of 1-(4-chlorobenzyl)-2-(pyrrolidin-1
      ylmethyl)-1H-benzimidazole (clemizole) were synthesized and evaluated as novel
      inhibitors of heme oxygenase (HO). Many of the compounds were found to be potent
      and highly selective for the HO-2 isozyme (constitutive), and had substantially
      less inhibitory activity on the HO-1 isozyme (inducible). The compounds represent
      the first report of highly potent and selective inhibitors of HO-2 activity, and
      complement our suite of selective HO-1 inhibitors. The study has revealed many
      candidates based on the inhibition of heme oxygenases for potentially useful
      pharmacological and therapeutic applications. 

PMID- 24021583
TI  - Open reduction and intramedullary stabilisation of subtrochanteric femur
      fractures: A retrospective study of 56 cases.
AB  - Subtrochanteric femur fractures commonly present with predictable displacement
      because of the deforming muscle forces acting upon the proximal femur. For this
      reason, successful closed reduction and femoral nailing can be a technically
      demanding procedure. Open reduction prior to nail placement has been advocated to
      improve and maintain anatomic fracture alignment. The purpose of this study was
      to evaluate the results of patients with closed subtrochanteric femur fractures
      treated with open reduction and a reamed antegrade statically locked
      intramedullary nail. An initial query of our database identified 154 patients who
      had sustained a subtrochanteric femur fracture over the defined study period.
      Ninety-six patients had adequate radiographic and clinical follow-up. Fifty-six
      (58%) patients were treated with open reduction and nail placement. There were no
      wound complications or infections and all patients went on to successful osseous
      union. There was no loss of reduction and a final coronal and sagittal plane
      deformity of <5 degrees in 55 of 56 (98%) patients. Open reduction of closed
      subtrochanteric femur fractures followed by intramedullary nailing leads to high
      union rates with rare complications. 

PMID- 24021582
TI  - Discovery and characterization of NVP-QAV680, a potent and selective CRTh2
      receptor antagonist suitable for clinical testing in allergic diseases.
AB  - Optimization of a 7-azaindole-3-acetic acid CRTh2 receptor antagonist chemotype
      derived from high throughput screening furnished a highly selective compound NVP
      QAV680 with low nM functional potency for inhibition of CRTh2 driven human
      eosinophil and Th2 lymphocyte activation in vitro. The molecule exhibited good
      oral bioavailability in the rat, combined with efficacy in rodent CRTh2-dependent
      mechanistic and allergic disease models and was suitable for clinical
      development. 

PMID- 24021584
TI  - Functional outcomes following syndesmotic fixation: A comparison of screws
      retained in situ versus routine removal - Is it really necessary?
AB  - INTRODUCTION: Syndesmotic disruption can occur in up to 20% of ankle fractures
      and is more common in Weber Type C injuries. Syndesmotic repair aims to restore
      ankle stability. Routine removal of syndesmosis screws is advocated to avoid
      implant breakage and adverse functional outcome such as pain and stiffness, but
      conflicting evidence exists to support this. The aim of the current study is to
      determine whether functional outcome differs in patients who had syndesmosis
      screws routinely removed, compared to those who did not, and whether a cost
      benefit exists if removal of screws is not routinely necessary. PATIENTS AND
      METHODS: A retrospective review of consecutive syndesmosis repairs was performed
      from 1 January 2008 to 31 December 2010 in a single regional trauma centre. We
      identified 91 patients who had undergone open reduction internal fixation of an
      ankle fracture with placement of a syndesmosis screw at index procedure. As many
      as 69 patients were eligible for the study as defined by the inclusion criteria
      and they completed a validated functional outcome questionnaire. The functional
      outcomes of patients with 'retained screws' and 'removed screws' were analysed
      and compared using the Olerud Molander Ankle Score (OMAS). RESULTS: A total of 63
      patients responded with a mean follow-up period of 31 months (range 10-43
      months). Of those patients, 43 underwent routine screw removal whilst 20 had
      screws left in situ. The groups were comparable considering age, gender and
      follow-up time. The 'retained' group scored higher mean OMAS scores, 81.5+/-19.3
      compared to 75+/-12.9 in the 'removed' group (p=0.107). The retained group
      achieved higher functional scores in each of the OMAS domains as well as
      experiencing less pain. When adjusted for gender, the findings were found to be
      statistically significant (p=0.046). CONCLUSION: Our study has shown that
      retained-screw fixation does not significantly impair functional capacity, with
      additional cost-effectiveness. We therefore advocate that syndesmosis screws be
      left in situ and should only be removed in case of symptomatic implants beyond 6
      months postoperatively.

PMID- 24021585
TI  - High proportions of CD4+ T cells among residual bone marrow T cells in childhood
      acute lymphoblastic leukemia are associated with favorable early responses.
AB  - Residual nonmalignant T cells in the bone marrow of patients with acute leukemias
      may be involved in active immune responses to leukemic cells. Here, we
      investigated the phenotypic signature of T cells present at diagnosis in 39
      pediatric patients with acute lymphoblastic leukemia (ALL) treated within
      standardized ALL-BFM study protocols. Previously described age associations of
      lymphocyte subpopulations in the peripheral blood of healthy children were
      reproduced in leukemic bone marrow. Analysis of individual lymphocyte parameters
      and risk-associated variables using univariate linear regression models revealed
      a correlation of higher CD4/CD8 ratios at diagnosis with a favorable bone marrow
      response on day 15. Separate analysis of CD4+ cells with the CD4+CD25(hi)FoxP3+
      T(reg) cell phenotype showed that the association was caused by non-T(reg) CD4+
      cells. The association of higher CD4/CD8 ratios with a favorable bone marrow
      response on day 15 of treatment persisted in a cohort extended to 69 patients. We
      conclude that CD4+ non-T(reg) cells in leukemic bone marrow at diagnosis may have
      a role in early response to treatment. Prospective analysis of the CD4/CD8 ratio
      in a large cohort of pediatric patients is now needed. Moreover, future
      experiments will establish the functional role of the individual T cell subsets
      in immune control in pediatric ALL.

PMID- 24021586
TI  - Retinal pigment epithelium cells produce VEGF in response to oxidized
      phospholipids through mechanisms involving ATF4 and protein kinase CK2.
AB  - Oxidized phospholipids (OxPLs) are pleiotropic lipid mediators known to induce
      proangiogenic and proinflammatory cellular effects that are increasingly
      recognized to be involved in a number of physiologic and pathologic processes in
      the retina. Immunohistochemical studies have detected OxPLs in retinal
      structures, such as retinal pigment epithelium (RPE) or photoreceptor cells. This
      study analyzed whether OxPLs could play a role in upregulation of VEGF, which is
      a cause of pathological neovascularization characteristic of eye diseases such as
      age-related macular degeneration. We confirmed accumulation of OxPLs in the eye
      using reversed-phase liquid chromatography coupled to mass spectrometry. Multiple
      species of oxidized phosphatidylcholines (OxPCs) were detected in human vitreous,
      including biologically active fragmented species POVPC, PGPC, PONPC and PAzPC. In
      in vitro experiments human fetal RPE and primary RPE cells were stimulated with
      OxPLs. Primary RPE cells were transfected with small interfering RNAs targeting
      ATF4. mRNA levels of VEGF in fetal and primary RPE cells were determined by real
      time quantitative PCR. VEGF protein concentrations were measured in culture
      medium by ELISA. We found that OxPCs and other classes of OxPLs upregulated the
      expression of VEGF in fetal and primary RPE cells, which critically depended on
      ATF4. In addition, upregulation of VEGF in primary RPE cells was blocked by a
      chemical inhibitor of protein kinase CK2 known to suppress induction of ATF4 and
      VEGF by OxPLs. Our data show that different species of OxPLs, which are present
      in the human eye are capable of stimulating expression of VEGF in fetal and
      primary RPE cells via ATF4-dependent mechanisms. 

PMID- 24021587
TI  - Emergency airway research: using all tools to bridge the knowledge gaps.

PMID- 24021588
TI  - Effect of microthread design of dental implants on stress and strain patterns: a
      three-dimensional finite element analysis.
AB  - The aim of this study was to use finite element analysis (FEA) to assess the
      influence of microthread design at the implant neck on stress distribution in the
      surrounding bone. A commercially available implant with 3.5 mm diameter and 10.5
      mm length was selected and used as a model. For the purpose of designing the
      microthread implant model, microthreads were added to the implant neck in a
      computerized model. A force measuring 100 N was then applied to the entire
      surface of the abutment in the vertical direction. The results showed that in
      both models, stress was mainly concentrated at the cortical bone adjacent to the
      neck of the implant. Maximum stress values in the cortical bone surrounding the
      implant surface periphery were 12 and 6.25 MPa for the microthread and
      conventional models, respectively. In this study, we conclude that adding a
      microthread design at the implant neck decreased stress values in the adjacent
      bone.

PMID- 24021589
TI  - Construction and in vitro test of a new electrode for dentin resistance
      measurement.
AB  - It is necessary to reduce the tooth substance before treating a tooth with a
      dental crown. The preparation often requires reduction of the dentin. This
      results in a dentin wound and a thinner substance over the pulp, increases the
      risk of inflammation, and could result in necrosis of the pulp. To give the
      dentist information about the amount of dentin over the pulp during preparation,
      the Prepometer was developed. The function of this device is based on the
      measurement of the electric resistance of the tooth substance. The measuring
      behavior of the first-generation Prepometer is characterized by smaller values of
      electric resistance before reaching full contact of the measuring head to the
      dentin surface and the actual value RT. This measuring behavior can mislead
      inexperienced therapists with inaccurate values that suggest thinner dentin than
      the reality. In this study, a new electrode based on the technology of active
      guard drive was constructed to overcome this issue. The results show that
      improvement in the measuring behavior of the new electrode could be achieved,
      eliminating the earlier disadvantage of the Prepometer.

PMID- 24021590
TI  - Effects of anthropometric variables and electrode placement on the SEMG activity
      of the biceps brachii muscle during submaximal isometric contraction in arm
      wrestling.
AB  - Surface electromyography (SEMG) has been widely used to analyze the biceps
      brachii (BB) muscle during voluntary contraction, and the effect of the
      interelectrode distance has been studied. However, the effect of anthropometric
      variations and the placement of electrodes on the BB activity during arm
      wrestling (i.e., during isometric contraction at a submaximal intensity) has
      seldom been investigated. In this study, the BB strength throughout this type of
      static contraction was evaluated. The SEMG signals were recorded from three
      locations on the BB: the muscle belly (M), near proximal (P), and distal tendon
      (L) regions. Twenty subjects who participated in the experiment were divided into
      five groups (A, B, C, D, and E). The average SEMG, root mean square, and
      variability of the signal were calculated using the coefficient of variance. The
      results indicated that the M region was more active and exhibited increased
      signal consistency (10.91%) compared with the other two regions (P: 24.47% and L:
      19.13%). Significant differences were observed between the L and P regions and
      between the M and P regions (p<0.05); however, there were no differences between
      the M and L regions (p>0.05). The increase in the SEMG value in groups B and C
      was significant (p<0.05), whereas groups A, D, and E did not exhibit a
      significant increase (p>0.05). In addition, muscle size was the strongest
      predictor of strength compared with body weight and height. The results suggest
      that the M region displays considerable SEMG effects and signal reliability.
      Furthermore, the SEMG measurements were found to correlate strongly with the
      strength of the contractions and the muscle size, and not with weight and height.

PMID- 24021592
TI  - Proceedings BMT (Biomedizinische Technik) 2013 - Dreilandertagung der Deutschen,
      Schweizerischen und Osterreichischen Gesellschaft fur Biomedizinische Technik,
      Graz, Austria, August 2013.

PMID- 24021591
TI  - Nondestructive monitoring of tissue-engineered constructs.
AB  - Abstract Tissue engineering as a multidisciplinary field enables the development
      of living substitutes to replace, maintain, or restore diseased tissue and
      organs. Since the term was introduced in medicine in 1987, tissue engineering
      strategies have experienced significant progress. However, up to now, only a few
      substitutes were able to overcome the gap from bench to bedside and have been
      successfully approved for clinical use. Substantial donor variability makes it
      difficult to predict the quality of tissue-engineered constructs. It is essential
      to collect sufficient data to ensure that poor or immature constructs are not
      implanted into patients. The fulfillment of certain quality requirements, such as
      mechanical and structural properties, is crucial for a successful implantation.
      There is a clear need for new nondestructive and real-time online monitoring and
      evaluation methods for tissue-engineered constructs, which are applicable on the
      biomaterial, tissue, cellular, and subcellular levels. This paper reviews current
      established nondestructive techniques for implant monitoring including
      biochemical methods and noninvasive imaging. 

PMID- 24021593
TI  - Fetal volume at 11-14 gestational weeks: reference ranges and association with
      first trimester biochemical and biophysical markers.
AB  - AIMS: To establish reference ranges for fetal volume (FV) measured by three
      dimensional ultrasound (3D-US) at 11-14 weeks of gestation and to examine the
      possible association of FV with maternal/pregnancy characteristics and
      biochemical parameters. METHODS: Prospective observational study on 240 fetuses
      at 11-14 weeks. FV was measured by 3D-US using Virtual Organ Computer-Aided
      Analysis. Pearson correlation coefficient (cc) and regression analysis were used.
      RESULTS: FV increased exponentially with crown rump length and was unrelated to
      maternal weight (cc=-0.137, P=0.071), age (cc=0.009, P=0.899), parity (0.76),
      smoking status (t-test, P=0.149) and mode of conception (t-test, P=0.8). Z-scores
      (z) of FV was not associated with z-mean uterine artery pulsatility index (cc=
      0.026, P=0.733), log10 multiples of the median (MoM) free beta human chorionic
      gonadotrophin (cc=0.002, P=0.982), delta value (d) of nuchal translucency
      (cc=0.072, P=0.331) and d-fetal heart rate (cc=0.009, P=0.902), z-FV was
      significantly positively correlated with log10 MoM pregnancy associated plasma
      protein-A (PAPP-A; regression coefficient=1.420976, R2=0.0957, P<0.0001).
      CONCLUSIONS: FV is strongly related to PAPP-A even after adjustment for crown
      rump length with a mechanism unrelated to placental perfusion. FV is independent
      of the vast majority of first trimester parameters; hence, it is a promising
      marker of early fetal growth.

PMID- 24021594
TI  - Nicotinic modulation of serotonergic activity in the dorsal raphe nucleus.
AB  - Cholinergic signaling mediated by nicotinic receptors has been associated to a
      large number of physiological and behavioral processes such as learning, memory,
      attention, food-intake and mood disorders. Although it is well established that
      many nicotinic actions are mediated through an increase in serotonin (5-HT)
      release, the physiological mechanisms by which nicotine produces these effects
      are still unclear. The dorsal raphe nucleus (DRN) contains the major amount of 5
      HT neurons projecting to different parts of the brain. DRN also contains
      nicotinic acetylcholine receptors (nAChRs) located at somatic and presynaptic
      elements. Nicotine produces both inhibitory and excitatory effects on different
      subpopulations of 5-HT DRN neurons. In this review, we describe the presynaptic
      and postsynaptic mechanisms by which nicotine increases the excitability of DRN
      neurons as well as the subtypes of nAChRs involved. We also describe the
      inhibitory effects of nicotine and the role of 5-HT1A receptors in this effect.
      These nicotinic actions modulate the activity of different neuronal
      subpopulations in the DRN, changing the 5-HT tone in the brain areas where these
      groups of neurons project. Some of the physiological implications of nicotine
      induced 5-HT release are discussed.

PMID- 24021595
TI  - Structural snapshot of cyclic nucleotide binding domains from cyclic nucleotide
      sensitive ion channels.
AB  - Cyclic nucleotide-binding domains (CNBDs) that are present in various channel
      proteins play crucial roles in signal amplification cascades. Although atomic
      resolution structures of some of those CNBDs are available, the detailed
      mechanism by which they confer cyclic nucleotide-binding to the ion channel pore
      remains poorly understood. In this review, we describe structural insights about
      cyclic nucleotide-binding-induced conformational changes in CNBDs and their
      potential coupling with channel gating.

PMID- 24021596
TI  - Membrane protein stability depends on the concentration of compatible solutes--a
      single molecule force spectroscopic study.
AB  - Compatible solutes are small, uncharged, zwitter ionic, osmotically active
      molecules produced and accumulated by microorganisms inside their cell to
      counteract different kinds of environmental stress. They enhance protein
      stability without interfering with the metabolic pathways even at molar
      concentrations. In this paper, we report the stabilizing effects of compatible
      solutes, ectoine, betaine and taurine on membrane protein bacteriorhodopsin at
      different concentrations. Using atomic force microscopy based single molecule
      force spectroscopy the impact of the osmolytes was quantified by measuring the
      forces required to pull the protein out of the membrane and the change in the
      persistence lengths of the unfolded polypeptide chain. Increase in unfolding
      forces were observed, indicating the strengthening of intramolecular
      interactions, which are vital for protein stability. The decrease in persistence
      lengths was recorded and showed increasing tendencies of the polypeptide strand
      to coil up. Interestingly, it was revealed that these molecules have different
      stabilizing effects on protein unfolding at different concentrations. The results
      show that the unfolding of single protein provides insight to the structure
      dynamic relationship between the protein and compatible solute molecules at sub
      nanometer scale. This also helps to understand the molecular mechanism involved
      in protein stabilization by organic osmolytes.

PMID- 24021597
TI  - Role of the peroxisome proliferator-activated receptors (PPAR)-alpha, beta/delta
      and gamma triad in regulation of reactive oxygen species signaling in brain.
AB  - Overwhelming evidence shows that oxidative stress is a major cause in development
      of brain disorders. Low activity of the reactive oxygen species (ROS)-degrading
      system as well as high levels of oxidative damage markers have been observed in
      brain tissue of patients with neurodegenerative and other brain diseases to a
      larger extent than in healthy individuals. Many studies aimed to develop
      effective and safe antioxidant strategies for the therapy or prevention of brain
      diseases. Nevertheless, it became clear that rigorous suppression of ROS is
      deleterious for normal cell functioning. Thus, approaches that can regulate the
      ROS levels over a wide range, from inhibition to induction, will be a powerful
      tool for neuroprotection. A most prominent target for such ROS management is the
      family of peroxisome proliferator-activated receptors (PPARs). All three members
      (PPAR-alpha, -beta/delta and -gamma) of this nuclear receptor subfamily form a
      tightly connected triad. For individual PPAR isoforms, neuroprotective properties
      have been well proven. Their involvement in regulation of ROS production and
      degradation underlies the therapeutic effects. Nevertheless, the current
      paradigms of the involvement of PPAR in neuroprotective therapy ignore such
      interconnections of PPARs and aim at antioxidant effects of individual PPAR
      isoforms, but do not take into account the necessity of careful regulation of ROS
      levels. The present review (i) summarizes the data, which support the concept of
      the PPAR triad in brain, (ii) demonstrates that usage of the PPAR triad allows
      the regulation of PPAR-dependent genes over a wide range, from inhibition to
      upregulation, and (iii) summarizes the known data concerning the PPAR triad
      involvement in regulation of ROS. Our report opens new directions in the field of
      PPAR/ROS-related neuroscience research.

PMID- 24021598
TI  - Enrichment and enumeration of circulating tumor cells by efficient depletion of
      leukocyte fractions.
AB  - BACKGROUND: Enumeration and characterization of circulating tumor cells (CTCs)
      can provide information on patient prognosis and treatment efficacy. However,
      CTCs are rare, making their isolation a major technological challenge. We
      developed a technique for enrichment, and subsequent characterization of CTCs
      based on efficient depletion of human leukocytes. METHODS: The technique
      (CanPatrolTM CTC enrichment) we developed is based on red blood cell lysis to
      remove erythrocytes, followed by depletion of CD45+ leukocytes using a magnetic
      bead separation method, and subsequent isolation of CTCs by virtue of their
      larger size, compared with leukocytes. We also demonstrated that fluorescence in
      situ hybridization (FISH) and genetic abnormalities analysis could be performed
      on the isolated CTCs. RESULTS: The spiking experiments showed that the average
      efficacy of leukocytes depletion was 99.98% and the average tumor cells recovery
      was not lower than 80%. FISH could be used to perform ALK gene rearrangement
      analysis on the collected NCI-H2228 cells, and EGFR Exon 19 deletion was detected
      by PCR-based analysis in isolated HCC827 cells. The in vivo feasibility of this
      technique had been demonstrated in patients with non-small cell lung cancer,
      breast, colon, and esophageal cancers. CTCs were detected in 13 of 59 blood
      samples. Tumor microemboli was also detected in three breast cancer samples.
      CONCLUSIONS: The technique we developed allowed isolation and characterization of
      circulating epithelial tumor cells that do not express classical epithelial
      antigens. This potentially leads to a more accurate enumeration of the number of
      CTCs and is suitable for application to a broad range of cancers.

PMID- 24021600
TI  - Chemiluminescence-based cobalamin assay errors: background and perspectives.

PMID- 24021599
TI  - Quantification of EGFR autoantibodies in the amplification phenomenon of HER2 in
      breast cancer.
AB  - BACKGROUND: Gene amplification or overexpression of human epidermal growth factor
      receptor HER2/ErB2 is seen in 25-30% of patients with breast cancer and is
      related to an aggressive disease. The mechanism behind the HER2 gene
      amplification is unknown, but it may be caused by continuous stimulation and
      activation. We hypothesised that autoantibodies against EGFR might have a
      stimulatory effect. To investigate this we developed a quantitative method to
      measure autoantibodies against EGFR in serum (S-EGFRAb). METHODS: Serum samples
      from primary breast cancer patients were selected based on the degree of HER2
      protein and gene amplification in the cancer tissue. Fifty patients had low
      levels of HER2 (<= 16 ng/mg total protein) and no HER2 gene amplification; 43
      patients had high levels of HER2 (>= 200 ng/mg total protein) and HER2 gene
      amplification. Serum was also collected from controls consisting of 50 healthy
      age-matched women. An ELISA was developed to measure S-EGFRAb quantitatively.
      RESULTS: No significant differences in S-EGFRAb concentrations were seen between
      patients with high and low levels of HER2 or between the patients and the
      controls. Furthermore, no significant correlations were observed between S-EGFRAb
      and stage, differentiation state, age or prognosis. A negative correlation
      (p=0.0022) was found between S-EGFRAb and disease free survival in the group of
      patients with relapse or death. CONCLUSIONS: S-EGFRAb can be measured accurately
      using the ELISA we developed. We conclude that autoantibodies against EGFR do not
      seem to be associated with the HER2 gene amplification phenomenon.

PMID- 24021601
TI  - The technological development history and current significance of the "physical
      BEMER(r) vascular therapy" in medicine.

PMID- 24021602
TI  - Effects of physical stimulation of spontaneous arteriolar vasomotion in patients
      of various ages undergoing rehabilitation.
AB  - On two samples of rehabilitation patients of different age groups (approx. 38
      years and approx. 51 years), via a placebo-controlled study series using
      representative features of microcirculation, the complementary therapeutic
      success of additional treatment complementing the biorhythmically defined
      physical vasomotion stimulation was determined. The results showed that in older
      rehabilitation patients the amounts of characteristic microcirculatory changes
      were greater than in younger persons undergoing rehabilitation, but they would
      subside faster after termination of the additional treatment than in the younger
      group.

PMID- 24021603
TI  - Influence of a specific, biorhythmically defined physical stimulus on deficient
      vasomotion in small-caliber arterioles in the subcutis in patients with diabetic
      polyneuropathy.
AB  - As part of a placebo-controlled study series on a random sample of patients with
      diabetic polyneuropathy and trophic skin lesions on the edge of the foot,
      functional characteristics of the local microcirculation and immune system were
      measured to check the complementary-therapy success of biorhythmically defined
      vasomotion stimulation. Over a 30-day treatment period, complementary-therapy
      success was demonstrated for an additional physical vasomotion stimulation to
      increase the therapeutic success of established treatment concepts.

PMID- 24021604
TI  - Complementary-therapeutic stimulation of deficient autorhythmic arteriolar
      vasomotion by means of a biorhythmically physical stimulus on the
      microcirculation and the immune system in 50-year-old rehabilitation patients.
AB  - As part of a placebo-controlled study series, a random sample of 50-year-old
      rehabilitation patients was examined to determine whether the complementary use
      of a physical treatment method to stimulate arteriolar vasomotion would improve
      the therapeutic success of established measures for the purposes of physical
      conditioning. The result showed that both the microcirculatory blood-flow
      regulation and the (cellular) immune response could be affected in a therapy
      relevant manner through additional physical vasomotion stimulation.

PMID- 24021606
TI  - Effects of various physical treatment methods on arteriolar vasomotion and
      microhemodynamic functional characteristics in case of deficient regulation of
      organ blood flow. Results of a placebo-controlled, double-blind study.
AB  - As part of a placebo-controlled study, high-resolution measurement methods were
      used to examine, on the basis of representative functional characteristics of
      microcirculation, whether and to what extent six different, commercially
      available, physical treatment devices were suitable for influencing, through
      complementary therapy, deficient blood-flow regulation. Of the six commercially
      available devices tested, two proved to be ineffective and three not effective
      enough to be therapeutically relevant. Only in one device was it possible to show
      a complementary-therapeutic effect: the device uses a specific, biorhythmically
      defined stimulus for vasomotion.

PMID- 24021608
TI  - The invisible part of the iceberg: qualitative aspects of childhood vasculitis.
AB  - OBJECTIVES: The aim of this study was to develop a multidimensional assessment
      instrument named 'Juvenile Vasculitis Multidimensional Assessment Report' (J
      VAMAR) to measure all the domains of the vasculitis. In this qualitative study,
      it is primarily aimed to enrich the item generation for the J-VAMAR. METHODS:
      Twelve children with vasculitis and their mothers (n=12) were enrolled in this
      study. The data were collected using both a demographic data form and a semi
      structured interview form. The study was performed on individual patient face-to
      face interview. Data were analysed by grounded theory and the N Vivo 9 software
      program. RESULTS: Four categories were obtained. These categories were (i)
      physical effects of the illness, (ii) emotional effects of the illness, (iii)
      social effects of the illness and (iv) experienced challenges related to
      treatment process. In the physical effect category severe pain, physical
      limitations, weakness and fatigue; in emotional effect category thought of death,
      hopelessness and dissatisfaction about body image; in the social effects category
      decrease in academic performance, absenteeism to school and concealing the
      sickness from friends were the most common features. In the fourth category,
      subjects complained of lifelong drug use and frequency of daily drug
      consumptions. CONCLUSIONS: These results provide evidence-based data for the
      assessment of children with vasculitis by several domains including physical,
      emotional and social aspects as well as treatment protocols. The study provides
      the basis and/or justification for selecting the domains that the developing
      multidimensional instrument should include.

PMID- 24021607
TI  - Enhanced brain-derived neurotrophic factor signaling in the nucleus accumbens of
      juvenile rats.
AB  - Brain-derived neurotrophic factor (BDNF) signaling through its receptor,
      tropomyosin receptor kinase B (TrkB), plays a critical role in neural plasticity
      and its dysregulation in striatum and prefrontal cortex (PFC) has been implicated
      in the etiology of mental health disorders such schizophrenia and drug addiction.
      In the present study, we characterized age-dependent differences in BDNF
      signaling and TrkB expression within the nucleus accumbens (NAc), caudate putamen
      (CP) and PFC in rats and determined the effects of administration of the dopamine
      agonist, SKF 83959, which activates the Gq-coupled dopamine receptors, the
      dopamine D5 receptor and the D1-D2 receptor heteromer. As proBDNF binds with high
      affinity to the p75 neurotrophin receptor (p75NTR), expression levels of these
      proteins were also assessed. The present findings showed that juvenile rats (aged
      26-28 days) exhibited significantly elevated basal BDNF expression and activation
      of full-length TrkB (TrkBfull) in NAc compared to their adult counterparts, as
      evidenced by increased TrkBfull phosphorylation. These changes were concomitant
      with an increase in the relative expression of TrkBfull compared to the truncated
      isoform, TrkB.T1, in NAc and CP. Conversely, in PFC the basal expression of BDNF
      in juvenile rats was significantly lower than in adult rats with an elevated
      relative expression of TrkBfull. Acute administration of SKF 83959 to juvenile
      rats abolished the age-dependent differences in BDNF expression in NAc and PFC,
      and in the relative expression of TrkBfull in NAc and CP. Together these findings
      indicate that the expression and/or signaling of BDNF and TrkB in striatum and
      PFC of juvenile rats is fundamentally different from that of adult rats, a
      finding that may have implications in neuropsychiatric disorders that exhibit age
      dependent susceptibility such as schizophrenia and drug addiction. 

PMID- 24021609
TI  - Bio-relevant dissolution testing of hard capsules prepared from different shell
      materials using the dynamic open flow through test apparatus.
AB  - Current compendial dissolution and disintegrating testing is unable to mimic
      physiological conditions affecting gastric drug release from immediate release
      dosage forms. In order to obtain more realistic data, a novel test setup was
      developed that we term a 'dynamic open flow through test apparatus'. It is based
      on the previously described dissolution stress test device and attempts to
      simulate the intra-gastric dissolution conditions pertinent to immediate release
      dosage forms administered under fasting conditions with respect to flow rates,
      intra-gastric temperature profiles and gastric motility. The concept of the
      dynamic open flow through test apparatus has been tested using five different
      types of hard capsules: conventional hard gelatin capsules (HGC), three
      hypromellose based capsules (Vcaps, Vcaps Plus and DRcaps) and pullulan based
      capsules (Plantcaps). These were of different sizes but all contained 100mg
      caffeine in each formulation, adjusted to avoid buoyancy by addition of
      excipient. When the capsules were stressed in the apparatus under the dynamic
      flow conditions applying mild pressure simulating gastric motility, release from
      release from Vcaps Plus, Vcaps and Plantcaps capsules was very well comparable to
      HGC. Capsules are usually swallowed with cold water and the temperature
      dependency of release from gelatin was noted as a significant factor, since heat
      exchange in the stomach is slow. 

PMID- 24021610
TI  - Calibration of clinical prediction rules does not just assess bias.
AB  - OBJECTIVES: Calibration is often thought to assess the bias of a clinical
      prediction rule. In particular, if the rule is based on a linear logistic model,
      it is often assumed that an overestimation of all coefficients results in a
      calibration slope less than 1 and an underestimation in a slope larger than 1.
      STUDY DESIGN AND SETTING: We investigate the relation of the bias and the
      residual variation of clinical prediction rules with the typical behavior of
      calibration plots and calibration slopes, using some artificial examples.
      RESULTS: Calibration is not only sensitive to the bias of the clinical prediction
      rule but also to the residual variation. In some circumstances, the effects may
      cancel out, resulting in a misleading perfect calibration. CONCLUSION: Poor
      calibration is a clear indication of limited usefulness of a clinical prediction
      rule. However, a perfect calibration should be interpreted with care as this may
      happen even for a biased prediction rule.

PMID- 24021611
TI  - The smallest worthwhile effect of nonsteroidal anti-inflammatory drugs and
      physiotherapy for chronic low back pain: a benefit-harm trade-off study.
AB  - OBJECTIVE: The aim of this study was to determine the smallest worthwhile effects
      of two treatments for nonspecific low back pain (LBP). STUDY DESIGN AND SETTING:
      The benefit-harm trade-off method was used to estimate the smallest worthwhile
      effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and physiotherapy for
      LBP. Patients seeking care for chronic LBP were interviewed by telephone before
      treatment commenced and 4 weeks later. RESULTS: Patients need to see a median of
      30% (interquartile range [IQR]: 10-40) more improvement in pain and 20% (IQR: 10
      40) more improvement in disability than would occur without intervention to
      perceive the effect of NSAIDs are worthwhile. They would need to see 20% (IQR: 0
      30) more improvement on pain and disability over natural recovery to perceive
      that the effect of physiotherapy was worthwhile. There was no difference in
      estimates of the smallest worthwhile effect elicited at baseline and 4 weeks
      later. CONCLUSIONS: People with chronic back pain need to see larger effects on
      pain of NSAIDS than physiotherapy to consider the effects of these interventions
      worthwhile. These estimates of the smallest worthwhile effect can be used to
      interpret the findings of clinical trials and to design adequately powered
      clinical trials.

PMID- 24021612
TI  - The stepped wedge cluster randomized trial always requires fewer clusters but not
      always fewer measurements, that is, participants than a parallel cluster
      randomized trial in a cross-sectional design. In reply.

PMID- 24021613
TI  - Ultrasonic-assisted ultra-rapid synthesis of monodisperse meso-SiO2@Fe3O4
      microspheres with enhanced mesoporous structure.
AB  - A core-shell-type of meso-SiO2@Fe3O4 microsphere was synthesized via an
      ultrasonic-assisted surfactant-templating process using solvothermal synthesized
      Fe3O4 as core, tetraethoxysilane (TEOS) as silica source, and cetyltrimethyl
      ammonium bromide (CTAB) as templates. The samples were characterized by FT-IR,
      XRD, TEM, N2 adsorption-desorption technology, and vibrating sample magnetometer
      (VSM). The results show that as-prepared meso-SiO2@Fe3O4(E) and meso
      SiO2@Fe3O4(C) microspheres, treated by acetone extraction and high temperature
      calcination, respectively, still maintain uniform core-shell structure with
      desirable mesoporous silica shell. Therein, the meso-SiO2@Fe3O4(E) microspheres
      possess a distinct pore size distribution in 1.8-3.0 nm with large specific
      surface area (468.6 m(2)/g) and pore volume (0.35 cm(3)/g). Noteworthily, the
      coating period of this ultrasonic-assisted method (40 min) is much shorter than
      that of the conventional method (12-24 h). The morphology of microspheres and the
      mesoporous structure of silica shell are significantly influenced by initial
      concentration of CTAB (CCTAB), ultrasonic irradiation power (P) and ultrasonic
      irradiation time (t). The acceleration roles of ultrasonic irradiation take
      effect during the whole coating process of mesoporous silica shell, including
      hydrolysis-condensation process of TEOS, co-assembly of hydrolyzed precursors and
      CTAB, and deposition of silica oligomers. In addition, the use of ultrasonic
      irradiation is favorable for improving the homogeneity of silica shell and the
      monodispersity of meso-SiO2@Fe3O4 microspheres.

PMID- 24021614
TI  - The experience of a Tunisian referral centre in prenatal diagnosis of Xeroderma
      pigmentosum.
AB  - AIMS: Xeroderma pigmentosum (XP, OMIM 278700-278780) is one of the most severe
      genodermatoses and is relatively frequent in Tunisia. In the absence of any
      therapy and to better manage the disease, we aimed to develop a molecular tool
      for DNA-based prenatal diagnosis. METHODS: Six consanguineous Tunisian XP
      families (4 XP-A and 2 XP-C) have benefited from a prenatal diagnosis. Screening
      for mutations was performed by direct sequencing, while maternal-foetal
      contamination was checked by genotyping. RESULTS: Among the 7 prenatal diagnoses,
      4 foetuses were heterozygous for the screened mutation. Exclusion of
      contamination by maternal cells was checked. Mutations were detected at a
      homozygous state in the remaining cases, and the parents decided to terminate
      pregnancy. CONCLUSION: Our study illustrates the implementation of prenatal
      diagnosis for better health support of XP in Tunisia.

PMID- 24021615
TI  - Is there a role for HbA1c in predicting mortality and morbidity outcomes after
      coronary artery bypass graft surgery?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was is there a role for HbA1c in predicting
      morbidity and mortality outcomes after coronary artery bypass surgery? Eleven
      studies presented 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. The studies
      presented analyse the relationship between preoperative HbA1c levels and
      postoperative outcomes following coronary artery bypass graft (CABG) in diabetic,
      non-diabetic or mixed patient groups. Four studies found significant increases in
      early and late mortality at higher HbA1c levels, regardless of a preoperative
      diagnosis of diabetes. One study demonstrated that 30-day survival outcomes were
      significantly worse in patients with previously undiagnosed diabetes and elevated
      HbA1c compared with those with good control [HbA1c >6%; odds ratio 1.53,
      confidence interval (CI) (1.24-1.91); P = 0.0005]. However, four studies of early
      mortality outcomes in diabetic patients only showed no significant differences
      between patients with normal and those with deranged HbA1c levels (P = 0.99).
      There were mixed reports on morbidity outcomes. Three studies identified a
      significant increase in infectious complications in patients with poorly
      controlled HbA1c, two of which were irrespective of previous diabetic status
      [deep sternal wound infection (P = 0.014); superficial sternal wound infection (P
      = 0.007) and minor infections (P = 0.006) in poorly controlled diabetics only].
      Four studies presented outcomes for total length of stay (LOS). Three of these
      papers looked specifically at diabetic patients, of which two found no
      significant differences in length of stay between good and poor preoperative
      glycaemic control [LOS: P = 0.59 and 0.86 vs P < 0.001]. However, elevated HbA1c
      vs normal HbA1c was associated with prolonged stay in hospital and in intensive
      care unit (ICU) in patients irrespective of previous diabetic status [total LOS
      (P < 0.001)]. Elevated HbA1c levels were also a significant predictor of reduced
      intraoperative insulin sensitivity in diabetic patients (R = -0.527; P < 0.001).
      Furthermore, higher HbA1c levels were associated with a reduced incidence of
      postoperative atrial fibrillation (P = 0.001). We conclude that elevated HbA1c is
      a strong predictor of mortality and morbidity irrespective of previous diabetic
      status. In particular, the mortality risk for CABG is quadrupled at HbA1c levels
      >8.6%. Some studies have called into question the predictive value of HbA1c on
      short-term outcomes in well-controlled diabetics; however, long-term outcomes in
      this population have not been reported. 

PMID- 24021617
TI  - Could Pin1 help us conquer essential hypertension at an earlier stage? A
      promising early-diagnostic biomarker and its therapeutic implications for the
      disease.
AB  - Essential hypertension is a major risk factor for cardiovascular morbidity and
      mortality, and the early-diagnosis is very important for the prevention of
      essential hypertension. Previously, we found that Pin1, the only known enzyme
      isomerizing pSer/pThr-Pro motifs in proteins, may gradually become inactive under
      conditions of stress such as intracellular acidification and fever.
      Interestingly, essential hypertension and the dysfunction of Pin1 often
      synchronously occur with the increasing age. Recent evidence indicates that Pin1
      primarily increases the activity of endothelial nitric oxide synthase (eNOS) and
      the production of nitric oxide (NO) in multiple ways, significantly promoting the
      relaxation response of blood vessels and preventing the elevation of blood
      pressure. Further, the inhibition of Pin1 results in significantly increased
      blood pressure in rats. So, we hypothesized and evaluated the potential of Pin1
      to be a new early-diagnostic biomarker as well as a therapeutic drug for
      essential hypertension. The unique activity of Pin1 and some epidemiological and
      experimental data evidence that the decreased activity of Pin1 may be closely
      associated with the development of essential hypertension. The factors that may
      impact the activity of Pin1 and correlate with the risk of essential hypertension
      were also discussed. These findings indicate that Pin1 plays a key and permanent
      role in efficiently preventing the development of essential hypertension, and
      that Pin1 may be a promising early-diagnostic biomarker as well as an effective
      therapeutic drug for the early-diagnosis, prevention, and treatment of essential
      hypertension, potentially decreasing the risk of cardiovascular morbidity and
      mortality. 

PMID- 24021616
TI  - Diabetes insipidus contributes to traumatic brain injury pathology via CD36
      neuroinflammation.
AB  - Each year, over one million people in the United States are affected by traumatic
      brain injury (TBI). Symptoms of both acute and chronic neuroinflammation follow
      TBI, coinciding with a robust immune response and activation of the brain's
      endogenous repair mechanisms. TBI can lead to endocrine failure as a result of
      damage to the thalamic region of the brain, evidenced by excessive thirst and
      polyuria often accompanying TBI. These symptoms indicate the presence of diabetes
      insipidus (DI), a disruption of water homeostasis due to antidiuretic hormone
      deficiency. This deficiency accompanies a mechanical or neuroinflammatory damage
      to the thalamic region during TBI, evidenced by increased expression of
      inflammatory microglial marker MHCII in this brain region. Excessive thirst and
      urinations, which are typical DI symptoms, in our chronic TBI rats also suggest a
      close connection between TBI and DI. We seek to bridge this gap between TBI and
      DI through investigation of the Cluster of Differentiation 36 (CD36) receptor.
      This receptor is associated with Low-Density Lipoprotein (LDL) deregulation, pro
      inflammatory events, and innate immunity regulation. We posit that CD36
      exacerbates TBI through immune activation and subsequent neuroinflammation.
      Indeed, scientific evidence already supports pathological interaction of CD36 in
      other neurological disorders including stroke and Alzheimer's disease. We propose
      that DI contributes to TBI pathology via CD36 neuroinflammation. Use of CD36 as a
      biomarker may provide insights into treatment and disease pathology of TBI and
      DI. This unexplored avenue of research holds potential for a better understanding
      and treatment of TBI and DI. 

PMID- 24021618
TI  - Acute cauda equina syndrome secondary to lumbar chordoma: case report and
      literature review.
AB  - BACKGROUND CONTEXT: Chordomas are rare tumors in the craniospinal axis arising
      from persistent notochordal rests commonly seen in the skull base, including the
      clivus and the sacrum. Chordomas in the mobile spine occur less commonly. To the
      best of our knowledge, the clinical presentation of acute cauda equina syndrome
      (CES) due to chordoma of the lumbar vertebra is not published in the English
      literature. PURPOSE: To describe an unusual cause of acute CES resulting from
      chordoma of the lumbar vertebra and discuss management dilemmas in this clinical
      context. STUDY DESIGN: Case report with review and discussion. METHODS: We report
      the case of a 75-year-old man who presented with acute CES that was clinically
      considered a metastasis from his previously documented carcinoma of the urinary
      bladder treated a year ago. Clinical, radiological, and histopathological
      features of the case and a review of chordomas in the lumbar vertebrae in adults
      in the published English literature are presented. RESULTS: He underwent urgent
      surgical decompression with laminectomy of L3/L4 and L4/L5 with debulking and
      open biopsy of the tissue mass. Histopathological examination of the tissue mass
      confirmed the unsuspected diagnosis of chordoma. The salient features of
      chordomas in the lumbar vertebrae published in the English literature over the
      last 22 years are summarized. The origin, classification, clinical presentation,
      and management protocols for lumbar chordomas are also reviewed. CONCLUSIONS: The
      clinical presentation of acute CES as the first symptom of chordoma in the lumbar
      vertebrae is extremely rare. Preoperative tissue diagnosis of this uncommon
      pathology is usually unavailable. In the face of acute CES, surgical
      decompression remains the primary goal of management with a planned definitive
      second-stage curative surgical resection for chordoma.

PMID- 24021619
TI  - Factors determining cervical spine sagittal balance in asymptomatic adults:
      correlation with spinopelvic balance and thoracic inlet alignment.
AB  - BACKGROUND CONTEXT: Based on the previous studies, cervical lordosis (CL) is a
      parameter influenced by thoracic kyphosis (TK); however, the correlations still
      remain unclear. Few studies have analyzed the correlations between the cervical
      spine lordosis and global spinopelvic balance. To date, there has been no study
      focused on the factors determining cervical spine sagittal balance. PATIENT
      SAMPLE: Seventy-seven asymptomatic volunteers without the history of symptoms
      related to whole spine. OUTCOME MEASURES: Statistical significance of
      correlations of radiographic parameters on cervical spine and whole-spine
      standing lateral radiograph. PURPOSE: To analyze the factors determining cervical
      spine sagittal balance, including global spinopelvic balance and thoracic inlet
      (TI) alignment in asymptomatic adults. STUDY DESIGN: A prospective radiographic
      study. METHODS: Cervical and whole-spine standing lateral radiographs were taken
      to analyze the following parameters: spinopelvic parameters pelvic incidence
      (PI), sacral slope (SS), lumbar lordosis (LL), and TK; TI parameters thoracic
      inlet angle (TIA) and T1 slope; and cervical spine parameters C0-C2, C2-C7, and
      C0-C7 angles and cervical tilting. Statistical analysis was performed using the
      Pearson correlation coefficients and multiple regression analysis. RESULTS: All
      the parameters showed a normal distribution. There was a significant sequential
      linkage between PI and SS (r=0.653), SS and LL (r=0.807), LL and TK (r=-0.516),
      and TK and C0-C7 angle (r=-0.322). There was a significant relationship between
      TK and T1 slope (r=0.351) but no significant relationship between TK and TIA.
      There were significant sequential relationships between TIA and T1 slope
      (r=0.694), T1 slope and C2-C7 angle (r=-0.624), and C2-C7 and C0-C2 angles (r=
      0.547). T1 slope was the only parameter that demonstrated a significant
      correlation with both SP and TI parameters. A linear regression model showed that
      T1 slope had a stronger relationship with TIA (r=0.694) than TK (r=0.351).
      CONCLUSIONS: T1 slope was a key factor determining cervical spine sagittal
      balance. Both spinopelvic balance and TI alignment have a significant influence
      on cervical spine sagittal balance via T1 slope, but TIA had a stronger effect
      than TK. An individual with large T1 slope required large CL to preserve
      physiologic sagittal balance of the cervical spine. The results of the present
      study could serve as baseline data for further studies on the cervical spine
      sagittal balance in various clinical conditions including the surgical
      reconstruction of lordosis.

PMID- 24021620
TI  - Sagittal range of motion after extensive cervical fusion.
AB  - BACKGROUND CONTEXT: Complicated cervical spine revision and deformity correction
      surgeries are becoming increasingly common. These challenging operations often
      necessitate fusion of the entire cervical spine. Patients frequently express
      concern over the likely loss of range of motion (ROM) of the neck
      postoperatively. However, we are aware of no study that specifically examines the
      sagittal cervical ROM after extensive cervical fusion. PURPOSE: To characterize
      sagittal ROM after extensive cervical fusion. STUDY DESIGN: Retrospective case
      series. PATIENT SAMPLE: Thirty patients were included. OUTCOME MEASURES:
      Radiographs at final follow-up were measured for cervical ROM by the
      occipitocervical and cervicosternal angles with the neck in full flexion and
      extension. METHODS: The surgical and medical records at one tertiary referral
      academic institution were used to identify adults who had undergone extensive
      cervical fusion between 1996 and 2008. An "extensive cervical fusion" entailed an
      upper instrumented vertebra proximal to C3 and lower instrumented vertebra distal
      to C7. Radiographs at final follow-up were measured for cervical ROM by the
      occipitocervical and cervicosternal angles with the neck in full flexion and
      extension. RESULTS: The average age at surgery was 58.3+/-10.0 years. The
      surgical levels were occiput-T1 (one patient), occiput-T4 (one patient), occiput
      T6 (one patient), C1-T1 (one patient), C1-T2 (one patient), C2-T1 (nine
      patients), C2-T2 (eight patients), C2-T3 (six patients), and C2-T4 (two
      patients). Twenty-seven of the procedures were revisions. The other surgical
      indications were chin-on-chest deformity (one patient), cervical scoliosis (one
      patient), and multilevel cervical myelopathy (one patient). The mean follow-up
      period was 34.5+/-30.9 months (range, 6-154 months). The mean cervical ROM values
      by the occipitocervical and cervicosternal angles were 29.5+/-11.0 degrees  and
      7.5+/-5.0 degrees , respectively. The mean total cervical ROM value was 34.1+/
      14.7 degrees . CONCLUSIONS: A substantial degree of sagittal ROM can be
      maintained after extensive surgical fusion of the cervical spine.

PMID- 24021621
TI  - Age-related sex differences in erector spinae muscle endurance using surface
      electromyographic power spectral analysis in healthy humans.
AB  - BACKGROUND CONTEXT: Previous studies reported that the erector spinae muscle is
      more resistant to fatigue in healthy adult women than in men. However, no study
      has reported changes in back muscle fatigue with aging in healthy men and women.
      PURPOSE: The aim of this study was to evaluate age-related changes in muscle
      fatigue of erector spinae muscle in men and women. STUDY DESIGN/SETTING: This
      cross-sectional study was conducted in a laboratory. PATIENT SAMPLE: Fifty-three
      healthy subjects (11 elderly men, 11 elderly women, 17 young men, and 14 young
      women) without low back pain history. OUTCOME MEASURES: The median frequency (MF)
      and mean power frequency (MPF) during trunk holding test were derived from the
      raw electromyographic (EMG) signal using Fast Fourier Transform spectrum analysis
      program. The rates of changes in MF and MPF were calculated. METHODS: Subjects
      performed the unsupported trunk holding test until exhaustion. The results of
      power spectral analysis of the EMG activity of the left erector spinae muscle
      were compared in both age groups and sexes. RESULTS: The endurance time in young
      men was significantly shorter than in young women. The slopes of MF and MPF in
      young men were significantly higher than in young women. There were no
      significant differences in MF and MPF slopes of elderly men and elderly women.
      Furthermore, the MF and MPF slopes were significantly lower in elderly men than
      young men but similar in the two women groups. CONCLUSIONS: Age-related changes
      in the slopes of MF and MPF of erector spinae muscle occur in healthy men but not
      in healthy women.

PMID- 24021622
TI  - Helical repeats modular proteins are major players for organelle gene expression.
AB  - Mitochondria and chloroplasts are often described as semi-autonomous organelles
      because they have retained a genome. They thus require fully functional gene
      expression machineries. Many of the required processes going all the way from
      transcription to translation have specificities in organelles and arose during
      eukaryote history. Most factors involved in these RNA maturation steps have
      remained elusive for a long time. The recent identification of a number of novel
      protein families including pentatricopeptide repeat proteins, half-a
      tetratricopeptide proteins, octotricopeptide repeat proteins and mitochondrial
      transcription termination factors has helped to settle long-standing questions
      regarding organelle gene expression. In particular, their functions have been
      related to replication, transcription, RNA processing, RNA editing, splicing, the
      control of RNA turnover and translation throughout eukaryotes. These families of
      proteins, although evolutionary independent, seem to share a common overall
      architecture. For all of them, proteins contain tandem arrays of repeated motifs.
      Each module is composed of two to three alpha-helices and their succession forms
      a super-helix. Here, we review the features characterising these protein
      families, in particular, their distribution, the identified functions and mode of
      action and propose that they might share similar substrate recognition
      mechanisms. 

PMID- 24021623
TI  - Management of fractures of the mandibular body and symphysis.
AB  - Mandibular fracture, specifically in the symphysis and body regions combined, is
      the most common facial fracture requiring hospitalization in North America. The
      primary treatment objective is to restore form and function by achieving anatomic
      reduction and placing fixation that eliminates mobility of the bone fragments.
      Several treatment options and surgical techniques are available for performing
      closed or open reduction. Special considerations are necessary when treating
      pediatric patients and fractures of the edentulous mandible. Complications
      relating to the tooth and denture-bearing regions of the mandible include
      infection, nonunion, and neurosensory changes. 

PMID- 24021624
TI  - Late reconstruction of orbital and naso-orbital deformities.
AB  - Acute orbital fractures and naso-orbital ethmoid fractures can result in chronic
      orbital and naso-orbital deformities. Understanding the acute injury is the first
      step in reconstructing the established late deformity. The best management
      strategy for reconstruction of orbital hypertelorism is to avoid late
      complications by repairing these deformities early near the time of the original
      fractures. New technologies from computer-guided surgical planning and additive
      manufacturing technology produce passive fitting implants tailored for patient
      specific needs. 

PMID- 24021625
TI  - Late reconstruction of condylar neck and head fractures.
AB  - Condyle fractures are a common injury, but only a few of these injuries require
      immediate or late reconstruction. The complications that most frequently
      necessitate condylar reconstruction include proximal segment degeneration,
      malunion, and ankylosis. Costochondral grafts and total joint prostheses, both
      stock and custom, remain the most common methods of reconstruction.
      Reconstruction plates with condylar extensions should only be used temporarily as
      an unacceptable number cause serious complications. Distraction osteogenesis may
      have an occasional role in reconstructing the posttraumatic condyle. 

PMID- 24021626
TI  - Helping anesthesiologists understand facial fractures.
AB  - Injuries to the oral and maxillofacial region are commonly encountered, and the
      appropriate management of patients with these injuries frequently requires the
      expertise of an anesthesiologist. Injuries to this region may involve any
      combination of soft tissue, bone, and teeth. Injuries to these structures often
      produce anesthesia-related challenges, which must be overcome to achieve optimal
      outcomes. This article addresses the common challenges faced by anesthesiologists
      specific to patients with facial fractures. 

PMID- 24021627
TI  - Unexpectedly broad target recognition of the CRISPR-mediated virus defence system
      in the archaeon Sulfolobus solfataricus.
AB  - The hyperthermophilic archaeon Sulfolobus solfataricus carries an extensive array
      of clustered regularly interspaced short palindromic repeats (CRISPR) systems
      able to mediate DNA degradation of invading genetic elements when complementarity
      to the small CRISPR-derived (cr)RNAs is given. Studying virus defence in vivo
      with recombinant viral variants, we demonstrate here that an unexpectedly high
      number of mutations are tolerated between the CRISPR-derived guide RNAs (crRNAs)
      and their target sequences (protospacer). Up to 15 mismatches in the crRNA still
      led to ~50% of DNA degradation, when these mutations were outside the 'seed'
      region. More than 15 mutations were necessary to fully abolished interference.
      Different from other CRISPR systems investigated in vivo, mutations outside the
      protospacer region indicated no need for a protospacer adjacent motif sequence to
      confer DNA interference. However, complementarity of only 3 nucleotides between
      the repeat-derived 5' handle of the crRNA and nucleotides adjacent to the
      protospacer enabled self-recognition, i.e. protection of the host locus. Our
      findings show commonalities and differences among the various CRISPR-mediated
      defence systems and suggest that they should not merely be perceived as a 'first
      barrier-defence system' but may be considered to have a broader mechanism that
      allows host cells to cope with viruses keeping them at reduced levels. 

PMID- 24021628
TI  - Structure-function analysis of Hmo1 unveils an ancestral organization of HMG-Box
      factors involved in ribosomal DNA transcription from yeast to human.
AB  - Ribosome biogenesis is a major metabolic effort for growing cells. In
      Saccharomyces cerevisiae, Hmo1, an abundant high-mobility group box protein
      (HMGB) binds to the coding region of the RNA polymerase I transcribed ribosomal
      RNAs genes and the promoters of ~70% of ribosomal protein genes. In this study,
      we have demonstrated the functional conservation of eukaryotic HMGB proteins
      involved in ribosomal DNA (rDNA) transcription. We have shown that when expressed
      in budding yeast, human UBF1 and a newly identified Sp-Hmo1 (Schizosaccharomyces
      pombe) localize to the nucleolus and suppress growth defect of the RNA polymerase
      I mutant rpa49-Delta. Owing to the multiple functions of both proteins, Hmo1 and
      UBF1 are not fully interchangeable. By deletion and domains swapping in Hmo1, we
      identified essential domains that stimulate rDNA transcription but are not fully
      required for stimulation of ribosomal protein genes expression. Hmo1 is organized
      in four functional domains: a dimerization module, a canonical HMGB motif
      followed by a conserved domain and a C-terminal nucleolar localization signal. We
      propose that Hmo1 has acquired species-specific functions and shares with UBF1
      and Sp-Hmo1 an ancestral function to stimulate rDNA transcription. 

PMID- 24021629
TI  - Sequence selectivity of the cleavage sites induced by topoisomerase I inhibitors:
      a molecular dynamics study.
AB  - Topoisomerase IB (Top1) inhibitors, such as camptothecin (CPT), stabilize the
      Top1-DNA cleavage complex in a DNA sequence-dependent manner. The sequence
      selectivity of Top1 inhibitors is important for targeting specific genomic
      sequences of therapeutic value. However, the molecular mechanisms underlying this
      selectivity remain largely unknown. We performed molecular dynamics simulations
      to delineate structural, dynamic and energetic features that contribute to the
      differential sequence selectivity of the Top1 inhibitors. We found the sequence
      selectivity of CPT to be highly correlated with the drug binding energies,
      dynamic and structural properties of the linker domain. Chemical insights, gained
      by per-residue binding energy analysis revealed that the non-polar interaction
      between CPT and nucleotide at the +1 position of the cleavage site was the major
      (favorable) contributor to the total binding energy. Mechanistic insights gained
      by a potential of mean force analysis implicated that the drug dissociation step
      was associated with the sequence selectivity. Pharmaceutical insights gained by
      our molecular dynamics analyses explained why LMP-776, an indenoisoquinoline
      derivative under clinical development at the National Institutes of Health,
      displays different sequence selectivity when compared with camptothecin and its
      clinical derivatives. 

PMID- 24021630
TI  - Defective chromatin recruitment and retention of NHEJ core components in human
      tumor cells expressing a Cyclin E fragment.
AB  - Exposure to genotoxic agents, such as ionizing radiation (IR), produces double
      strand breaks, repaired predominantly in mammalian cells by non-homologous end
      joining (NHEJ). Ku70 was identified as an interacting partner of a proteolytic
      Cyclin E (CycE) fragment, p18CycE. p18CycE endogenous generation during IR
      induced apoptosis in leukemic cells and its stable expression in epithelial tumor
      cells sensitized to IR. gammaH2AX IR-induced foci (IRIFs) and comet assays
      indicated ineffective NHEJ DNA repair in p18CycE-expressing cells. DNA pull-down
      and chromatin recruitment assays revealed that retention of NHEJ factors to
      double-strand breaks, but not recruitment, was diminished. Similarly, IRIFs of
      phosphorylated T2609 and S2056-DNA-PKcs and its target S1778-53BP1 were greatly
      decreased in p18CycE-expressing cells. As a result, DNA-PKcs chromatin
      association was also increased. 53BP1 IRIFs were suppressed when p18CycE was
      generated in leukemic cells and in epithelial cells stably expressing p18CycE.
      Ataxia telangiectasia mutated was activated but not its 53BP1 and MDC1 targets.
      These data indicate a profound influence of p18CycE on NHEJ through its
      interference with DNA-PKcs conformation and/or dimerization, which is required
      for effective DNA repair, making the p18CycE-expressing cells more IR sensitive.
      These studies provide unique mechanistic insights into NHEJ misregulation in
      human tumor cells, in which defects in NHEJ core components are rare. 

PMID- 24021632
TI  - Aging promotes progression of IgA nephropathy: a systematic review and meta
      analysis.
AB  - BACKGROUND: There has been considerable interest in whether old age is associated
      with IgA nephropathy (IgAN) progression, which is still controversial. METHODS:
      We searched multiple databases for studies published from 1980 to 2012. The
      inclusion criteria were case-control, cohort studies published in any language.
      The included studies needed to have an older group. IgAN was proven by biopsy.
      RESULTS: We included 9 studies with a total of 6,543 patients. The meta-analyses
      of other risk factors between the older group (>50 years old) and the non-older
      group (15-50 years old) found significant differences in the presence of
      hypertension, proteinuria, serum cholesterol levels and baseline renal function.
      In the overall analysis, compared to the non-older group, older age significantly
      increased the incidence of developing end-stage renal disease [ESRD; relative
      risk (RR) random model 1.95; 95% CI: 1.27-3.01]. In the subgroup analyses, we
      found the age limit and traditional risk factors of IgAN may be the sources of
      heterogeneity between studies. Moreover, the RR (2.56) of the Asian countries was
      much higher than the RR (1.11) of the European countries. CONCLUSIONS: This
      comprehensive review revealed that old age is a real risk factor for IgAN
      progression to ESRD. The incidence of ESRD in the older IgAN patients was 1.95
      times higher than that in the non-older IgAN patients. Moreover, the risk of IgAN
      progression to ESRD of the older patients in Asia was higher than that of the
      older patients in Europe.

PMID- 24021631
TI  - Optochemical control of RNA interference in mammalian cells.
AB  - Short interfering RNAs (siRNAs) and microRNAs (miRNAs) have been widely used in
      mammalian tissue culture and model organisms to selectively silence genes of
      interest. One limitation of this technology is the lack of precise external
      control over the gene-silencing event. The use of photocleavable protecting
      groups installed on nucleobases is a promising strategy to circumvent this
      limitation, providing high spatial and temporal control over siRNA or miRNA
      activation. Here, we have designed, synthesized and site-specifically
      incorporated new photocaged guanosine and uridine RNA phosphoramidites into short
      RNA duplexes. We demonstrated the applicability of these photocaged siRNAs in the
      light-regulation of the expression of an exogenous green fluorescent protein
      reporter gene and an endogenous target gene, the mitosis motor protein, Eg5. Two
      different approaches were investigated with the caged RNA molecules: the light
      regulation of catalytic RNA cleavage by RISC and the light-regulation of seed
      region recognition. The ability to regulate both functions with light enables the
      application of this optochemical methodology to a wide range of small regulatory
      RNA molecules. 

PMID- 24021634
TI  - Mathematical modeling of tumor growth, drug-resistance, toxicity, and optimal
      therapy design.
AB  - The combination of mathematical modeling and optimal control techniques holds
      great potential for quantitatively describing tumor progression and optimal
      treatment planning. Hereby, we use a Gompertz-type growth law and a
      pharmacokinetic-pharmacodynamic approach for modeling the effects of drugs on
      tumor progression in tumor bearing mice, and we combine these in order to design
      optimal therapeutic patterns. Specifically, we describe colon cancer progression
      in both untreated mice as well as mice treated with widely used anticancer
      agents. We also present a pharmacokinetic model to describe the kinetics of drugs
      in the body as well as detailed toxicity models to describe the severity of side
      effects. Finally, we propose a promising methodology by which cancer progression
      in mice with drug resistance can be controlled. By using optimal control, we
      demonstrate that the optimal planning of the frequency and magnitude of treatment
      interruptions is key to the control of cancer progression in subjects with
      resistance and should be further investigated in an experimental setting, which
      is currently underway.

PMID- 24021633
TI  - An optical fiber-based gating device for prospective mouse cardiac MRI.
AB  - Prospective synchronization of MRI acquisitions on living organisms involves the
      monitoring of respiratory and heart motions. The electrocardiogram (ECG) signal
      is conventionally used to measure the cardiac cycle. However, in some
      circumstances, obtaining an uncorrupted ECG signal recorded on small animals with
      radio frequency (RF) pulses and gradient switching is challenging. To monitor
      respiratory motion, an air cushion associated with a pressure sensor is commonly
      used but the system suffers from bulkiness. For many applications, the
      physiological gating information can also be derived from an MR navigated signal.
      However, a compact device that can simultaneously provide respiratory and cardiac
      information, for both prospective gating and physiological monitoring, is
      desirable. This is particularly valid since small volume coils or dedicated
      cardiac RF coil arrays placed directly against the chest wall are required to
      maximize measurement sensitivity. An optic-based device designed to synchronize
      MRI acquisitions on small animal's respiratory and heart motion was developed
      using a transmit-receive pair of optical fibers. The suitability of the developed
      device was assessed on mice ( n = 10) and was based on two sets of experiments
      with dual cardiac and respiratory synchronization. Images acquired with
      prospective triggering using the optical-based signal, ECG, and the pressure
      sensor during the same experiment were compared between themselves in the first
      set. The second set compared prospective technique using optical-based device and
      ECG to a retrospective technique. The optical signal that was correlated to both
      respiratory and heart motion was totally unaffected by radiofrequency pulses or
      currents induced by the magnetic field gradients used for imaging. Mice heart MR
      images depict low-visible motion artifacts with all sensors or techniques used.
      No significant SNR differences were found between each series of image. Full
      fiber-optic-based signal derived from heart and respiratory motion was suitable
      for prospective triggering of heart MR imaging. The fiber optic device performed
      similarly to the ECG and air pressure sensors, while providing an advantage for
      imaging with dedicated cardiac array coils by reducing bulk. It can be an
      attractive alternative for small animal MRI in difficult environments such as
      limited space and strong gradient switching. 

PMID- 24021636
TI  - Usability and Interoperability in Wireless Sensor Networks for Patient
      Telemonitoring in Chronic Disease Management.
AB  - This paper addresses two key technological barriers to the wider adoption of
      patient telemonitoring systems for chronic disease management, namely, usability
      and sensor device interoperability. As a great percentage of chronic patients are
      elderly patients as well, usability of the system has to be adapted to their
      needs. This paper identifies (from previous research) a set of design criteria to
      address these challenges, and describes the resulting system based on a wireless
      sensor network, and including a node as a custom-made interface that follows
      usability design criteria stated. This system has been tested with 22 users (mean
      age 65) and evaluated with a validated usability questionnaire. Results are good
      and improve those of other systems based on TV or smartphone. Our results suggest
      that user interfaces alternative to TVs and smartphones could play an important
      role on the usability of sensor networks for patient monitoring. Regarding
      interoperability, only very recently a standard has been published (2010, the ISO
      IEEE 11073 Personal health devices) that can support the needs of limited
      computational power environments typical of patient monitoring sensor networks. 

PMID- 24021635
TI  - GOM-Face: GKP, EOG, and EMG-based multimodal interface with application to
      humanoid robot control.
AB  - We present a novel human-machine interface, called GOM-Face , and its application
      to humanoid robot control. The GOM-Face bases its interfacing on three electric
      potentials measured on the face: 1) glossokinetic potential (GKP), which involves
      the tongue movement; 2) electrooculogram (EOG), which involves the eye movement;
      3) electromyogram, which involves the teeth clenching. Each potential has been
      individually used for assistive interfacing to provide persons with limb motor
      disabilities or even complete quadriplegia an alternative communication channel.
      However, to the best of our knowledge, GOM-Face is the first interface that
      exploits all these potentials together. We resolved the interference between GKP
      and EOG by extracting discriminative features from two covariance matrices: a
      tongue-movement-only data matrix and eye-movement-only data matrix. With the
      feature extraction method, GOM-Face can detect four kinds of horizontal tongue or
      eye movements with an accuracy of 86.7% within 2.77 s. We demonstrated the
      applicability of the GOM-Face to humanoid robot control: users were able to
      communicate with the robot by selecting from a predefined menu using the eye and
      tongue movements.

PMID- 24021637
TI  - A primigravida with single atrium and single ventricle.

PMID- 24021638
TI  - Improved Shear Wave Motion Detection Using Pulse-Inversion Harmonic Imaging With
      a Phased Array Transducer.
AB  - Ultrasound tissue harmonic imaging is widely used to improve ultrasound B-mode
      imaging quality thanks to its effectiveness in suppressing imaging artifacts
      associated with ultrasound reverberation, phase aberration, and clutter noise. In
      ultrasound shear wave elastography (SWE), because the shear wave motion signal is
      extracted from the ultrasound signal, these noise sources can significantly
      deteriorate the shear wave motion tracking process and consequently result in
      noisy and biased shear wave motion detection. This situation is exacerbated in in
      vivo SWE applications such as heart, liver, and kidney. This paper, therefore,
      investigated the possibility of implementing harmonic imaging, specifically pulse
      inversion harmonic imaging, in shear wave tracking, with the hypothesis that
      harmonic imaging can improve shear wave motion detection based on the same
      principles that apply to general harmonic B-mode imaging. We first designed an
      experiment with a gelatin phantom covered by an excised piece of pork belly and
      show that harmonic imaging can significantly improve shear wave motion detection
      by producing less underestimated shear wave motion and more consistent shear wave
      speed measurements than fundamental imaging. Then, a transthoracic heart
      experiment on a freshly sacrificed pig showed that harmonic imaging could
      robustly track the shear wave motion and give consistent shear wave speed
      measurements of the left ventricular myocardium while fundamental imaging could
      not. Finally, an in vivo transthoracic study of seven healthy volunteers showed
      that the proposed harmonic imaging tracking sequence could provide consistent
      estimates of the left ventricular myocardium stiffness in end-diastole with a
      general success rate of 80% and a success rate of 93.3% when excluding the
      subject with Body Mass Index higher than 25. These promising results indicate
      that pulse-inversion harmonic imaging can significantly improve shear wave motion
      tracking and thus potentially facilitate more robust assessment of tissue
      elasticity by SWE. 

PMID- 24021639
TI  - Fifteen-year assessment of a permeable reactive barrier for treatment of chromate
      and trichloroethylene in groundwater.
AB  - The fifteen-year performance of a granular iron, permeable reactive barrier (PRB;
      Elizabeth City, North Carolina) is reviewed with respect to contaminant treatment
      (hexavalent chromium and trichloroethylene) and hydraulic performance. Due to in
      situ treatment of the chromium source zone, reactive and hydraulic longevity of
      the PRB has outlived the mobile chromate plume. Chromium concentrations exceeding
      3 MUg/L have not been detected in regions located hydraulically down-gradient of
      the PRB. Trichloroethylene treatment has also been effective, although non
      constant influent concentrations of trichloroethylene have at times resulted in
      incomplete dechlorination. Daughter products: cis-1,2-dichloroethylene, vinyl
      chloride, ethene, and ethane have been observed within and down-gradient of the
      PRB at levels <10% of the influent trichloroethylene. Analysis of potentiometric
      surfaces up-gradient and across the PRB suggests that the PRB may currently
      represent a zone of reduced hydraulic conductivity; however, measurements of the
      in-situ hydraulic conductivity provide values in excess of 200 m/d in some
      intervals and indicate no discernible loss of bulk hydraulic conductivity within
      the PRB. The results presented here are particularly significant because they
      provide the longest available record of performance of a PRB. The longevity of
      the Elizabeth City PRB is principally the result of favorable groundwater
      geochemistry and hydrologic properties of the site.

PMID- 24021640
TI  - Cognitive dysfunction in antiphospholipid antibody (aPL)-negative systemic lupus
      erythematosus (SLE) versus aPL-positive non-SLE patients.
AB  - OBJECTIVES: The aim of this study was to compare the cognitive function of
      antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) and
      aPL-positive non-SLE patients. METHODS: Twenty aPL-negative SLE and 20 aPL
      positive non-SLE female patients with no history of overt neuropsychiatric
      manifestations took standardised cognitive tests of learning and memory,
      attention and working memory, executive functions, verbal fluency,
      visuoconstruction, and motor function. The primary outcome measure was an
      established global cognitive impairment index (CII). Cranial magnetic resonance
      imaging (MRI) was also obtained on all patients. RESULTS: Twelve of 20 (60%) of
      the SLE and 8/20 (40%) of the aPL-positive patients had global cognitive
      impairment on CII; there were no group differences on CII or on individual
      measures. Cognitive impairment was not associated with duration of disease, level
      of disease activity, or prednisone use. No correlations were found between
      clinical disease factors and cognitive impairment, and neither group showed an
      association between incidental or major MRI abnormalities and cognitive
      dysfunction. CONCLUSIONS: Both aPL-negative SLE and aPL-positive non-SLE
      patients, without other overt neuropsychiatric disease, demonstrated high levels
      of cognitive impairment. No clinical, serologic, or radiologic characteristics
      were associated with cognitive impairment. Cognitive dysfunction is common in APS
      and in SLE, but its mechanisms remain unknown.

PMID- 24021641
TI  - Phylogenetic analysis and substrate specificity of GH2 beta-mannosidases from
      Aspergillus species.
AB  - Phylogenetic analysis of glycoside hydrolase family 2 including Aspergillus
      sequences and characterised beta-mannosidases from other organisms, clusters
      putative Aspergillus beta-mannosidases in two distinct clades (A and B).
      Aspergillus species have at least one paralog in each of the two clades. It
      appears that clade A members are extracellular and clade B members intracellular.
      Substrate specificity analysis of MndA of Aspergillus niger (clade A) and MndB of
      Aspergillus nidulans (clade B) show that MndB, in contrast to MndA, does not
      hydrolyse polymeric mannan and has probably evolved to hydrolyse small unbranched
      beta-mannosides like mannobiose. A 3D-model of MndB provides further insight. 

PMID- 24021642
TI  - gammaH2AX foci formation in the absence of DNA damage: mitotic H2AX
      phosphorylation is mediated by the DNA-PKcs/CHK2 pathway.
AB  - Phosphorylated H2AX is considered to be a biomarker for DNA double-strand breaks
      (DSB), but recent evidence suggests that gammaH2AX does not always indicate the
      presence of DSB. Here we demonstrate the bimodal dynamic of H2AX phosphorylation
      induced by ionizing radiation, with the second peak appearing when G2/M arrest is
      induced. An increased level of gammaH2AX occurred in mitotic cells, and this
      increase was attenuated by DNA-PKcs inactivation or Chk2 depletion, but not by
      ATM inhibition. The phosphorylation-mimic CHK2-T68D abrogated the attenuation of
      mitotic gammaH2AX induced by DNA-PKcs inactivation. Thus, the DNA-PKcs/CHK2
      pathway mediates the mitotic phosphorylation of H2AX in the absence of DNA
      damage. 

PMID- 24021643
TI  - Structural and functional characterization of the single-chain Fv fragment from a
      unique HCV E1E2-specific monoclonal antibody.
AB  - The nucleotide sequence of the unique neutralizing monoclonal antibody D32.10
      raised against a conserved conformational epitope shared between E1 and E2 on the
      serum-derived hepatitis C virus (HCV) envelope was determined. Subsequently, the
      recombinant single-chain Fv fragment (scFv) was cloned and expressed in
      Escherichia coli, and its molecular characterization was assessed using multi
      angle laser light scattering. The scFv mimicked the antibody in binding to the
      native serum-derived HCV particles from patients, as well as to envelope E1E2
      complexes and E1, E2 glycoproteins carrying the viral epitope. The scFv D32.10
      competed with the parental IgG for binding to antigen, and therefore could be a
      promising candidate for therapeutics and diagnostics. 

PMID- 24021644
TI  - Understanding inositol pyrophosphate metabolism and function: kinetic
      characterization of the DIPPs.
AB  - We illuminate the metabolism and the cell-signaling activities of inositol
      pyrophosphates, by showing that regulation of yeast cyclin-kinase by 1-InsP7 is
      not conserved for mammalian CDK5, and by kinetically characterizing Ddp1p/DIPP
      mediated dephosphorylation of 1-InsP7, 5-InsP7 and InsP8. Each phosphatase
      exhibited similar Km values for every substrate (range: 35-148 nM). The rank
      order of kcat values (1-InsP7>5-InsP7=InsP8) was identical for each enzyme,
      although DIPP1 was 10- to 60-fold more active than DIPP2alpha/beta and
      DIPP3alpha/beta. We demonstrate InsP8 dephosphorylation preferentially progresses
      through 1-InsP7. Conversely, we conclude that the more metabolically and
      functionally significant steady-state route of InsP8 synthesis proceeds via 5
      InsP7.

PMID- 24021645
TI  - Aminoacylation of tRNA 2'- or 3'-hydroxyl by phosphoseryl- and pyrrolysyl-tRNA
      synthetases.
AB  - Class I and II aminoacyl-tRNA synthetases (AARSs) attach amino acids to the 2'-
      and 3'-OH of the tRNA terminal adenosine, respectively. One exception is
      phenylalanyl-tRNA synthetase (PheRS), which belongs to Class II but attaches
      phenylalanine to the 2'-OH. Here we show that two Class II AARSs, O-phosphoseryl-
      (SepRS) and pyrrolysyl-tRNA (PylRS) synthetases, aminoacylate the 2'- and 3'-OH,
      respectively. Structure-based-phylogenetic analysis reveals that SepRS is more
      closely related to PheRS than PylRS, suggesting that the idiosyncratic feature of
      2'-OH acylation evolved after the split between PheRS and PylRS. Our work
      completes the understanding of tRNA aminoacylation positions for the 22 natural
      AARSs. 

PMID- 24021646
TI  - Overexpression, purification, and functional analysis of recombinant human
      tubulin dimer.
AB  - Microtubules consisting of tubulin dimers play essential roles in various
      cellular functions. Investigating the structure-function relationship of tubulin
      dimers requires a method to prepare sufficient quantities of recombinant tubulin.
      To this end, we simultaneously expressed human alpha1- and beta3-tubulin using a
      baculovirus-insect cell expression system that enabled the purification of 5mg
      recombinant tubulin per litre of cell culture. The purified recombinant human
      tubulin could be polymerized into microtubules that glide on a kinesin-coated
      glass surface. The method provides a powerful tool for in vitro functional
      analyses of microtubules. 

PMID- 24021647
TI  - UXT plays dual opposing roles on SARM-induced apoptosis.
AB  - Apoptosis is a vital defense mechanism for the clearance of infected cells.
      Ubiquitously expressed transcript (UXT), which exists in two isoforms (V1 and
      V2), interact with both apoptotic and cellular proteins. By yeast two-hybrid
      analysis, we found that UXT interacts with SARM (sterile alpha and HEAT armadillo
      motif-containing protein). Since SARM is a TLR adaptor which induces intrinsic
      apoptosis following immune activation, we were prompted to query whether UXT and
      SARM might co-regulate apoptosis. We found that the UXT isoforms elicit dual
      opposing regulatory effects on SARM-induced apoptosis; while UXT V1, co-expressed
      with SARM, caused a reduction in caspase 8 activity, UXT V2 strongly increased
      caspase 8 activity and enhanced SARM-induced apoptosis by activating the
      extrinsic pathway and depolarizing the mitochondria. 

PMID- 24021648
TI  - Potassium ion-dependent trehalose phosphorylase from halophilic Bacillus
      selenitireducens MLS10.
AB  - We discovered a potassium ion-dependent trehalose phosphorylase (Bsel_1207)
      belonging to glycoside hydrolase family 65 from halophilic Bacillus
      selenitireducens MLS10. Under high potassium ion concentrations, the recombinant
      Bsel_1207 produced in Escherichia coli existed as an active dimeric form that
      catalyzed the reversible phosphorolysis of trehalose in a typical sequential bi
      bi mechanism releasing beta-D-glucose 1-phosphate and D-glucose. Decreasing
      potassium ion concentrations significantly reduced thermal and pH stabilities,
      leading to formation of inactive monomeric Bsel_1207.

PMID- 24021650
TI  - ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to
      ionizing radiation by stimulating proteasomal degradation of Rad51.
AB  - In this study, we provide evidence that endoplasmic reticulum (ER) stress
      suppresses DNA double-strand break (DSB) repair and increases radiosensitivity of
      tumor cells by altering Rad51 levels. We show that the ER stress inducer
      tunicamycin stimulates selective degradation of Rad51 via the 26S proteasome,
      impairing DSB repair and enhancing radiosensitivity in human lung cancer A549
      cells. We also found that glucose deprivation, which is a physiological inducer
      of ER stress, triggered similar events. These findings suggest that ER stress
      caused by the intratumoral environment influences tumor radiosensitivity, and
      that it has potential as a novel target to improve cancer radiotherapy. 

PMID- 24021651
TI  - Structure and function of the C-terminal domain of MrpA in the Bacillus subtilis
      Mrp-antiporter complex--the evolutionary progenitor of the long horizontal helix
      in complex I.
AB  - MrpA and MrpD are homologous to NuoL, NuoM and NuoN in complex I over the first
      14 transmembrane helices. In this work, the C-terminal domain of MrpA, outside
      this conserved area, was investigated. The transmembrane orientation was found to
      correspond to that of NuoJ in complex I. We have previously demonstrated that the
      subunit NuoK is homologous to MrpC. The function of the MrpA C-terminus was
      tested by expression in a previously used Bacillus subtilis model system. At
      neutral pH, the truncated MrpA still worked, but at pH 8.4, where Mrp-complex
      formation is needed for function, the C-terminal domain of MrpA was absolutely
      required. 

PMID- 24021649
TI  - The cytoplasmic domain of neuropilin-1 regulates focal adhesion turnover.
AB  - Though the vascular endothelial growth factor coreceptor neuropilin-1 (Nrp1)
      plays a critical role in vascular development, its precise function is not fully
      understood. We identified a group of novel binding partners of the cytoplasmic
      domain of Nrp1 that includes the focal adhesion regulator, Filamin A (FlnA).
      Endothelial cells (ECs) expressing a Nrp1 mutant devoid of the cytoplasmic domain
      (nrp1(cyto)(Delta/Delta)) migrated significantly slower in response to VEGF
      relative to the cells expressing wild-type Nrp1 (nrp1(+/+) cells). The rate of FA
      turnover in VEGF-treated nrp1(cyto)(Delta/Delta) ECs was an order of magnitude
      lower in comparison to nrp1(+/+) ECs, thus accounting for the slower migration
      rate of the nrp1(cyto)(Delta/Delta) ECs. 

PMID- 24021652
TI  - Infectious cerebral embolism.

PMID- 24021653
TI  - MK886 reduces cerebral amyloid angiopathy severity in TgCRND8 mice.
AB  - BACKGROUND: Deposition of amyloid-beta (Abeta) in blood vessel walls as cerebral
      amyloid angiopathy (CAA) is observed in the majority of Alzheimer's disease (AD)
      brains. Inhibition of the 5-lipoxygenase (5-LOX) pathway has recently been
      suggested to play a role in reducing parenchymal Abeta deposition. However,
      products of the 5-LOX pathway also activate the peroxisome proliferator-activated
      receptor (PPAR) family, which promotes clearance of Abeta from the brain.
      METHODS: In the present study, we investigated the effect of MK886, a 5-LOX
      activating protein (FLAP) inhibitor and PPARalpha antagonist, on CAA severity in
      TgCRND8 mice overexpressing the human Swedish and Indiana amyloid precursor
      protein mutations. RESULTS: We found that MK886 significantly reduced brain
      levels of nicastrin and PPARalpha, but did not affect levels of beta-secretase,
      apolipoprotein E or low-density lipoprotein receptor-related protein-1. CAA
      severity and parenchymal plaque load was significantly decreased in both the
      cortex and hippocampus of mice treated with MK886 compared to control mice.
      CONCLUSION: These data suggest that 5-LOX and FLAP inhibitors may be useful in
      the treatment of CAA and AD.

PMID- 24021654
TI  - A Low Power Linear Phase Programmable Long Delay Circuit.
AB  - A novel linear phase programmable delay is being proposed and implemented in a
      0.35 MUm CMOS process. The delay line consists of N cascaded cells, each of which
      delays the input signal by Td/N, where Td is the total line delay. The delay
      generated by each cell is programmable by changing a clock frequency and is also
      fully independent of the frequency of the input signal. The total delay hence
      depends only on the chosen clock frequency and the total number of cascaded
      cells. The minimum clock frequency is limited by the maximum time a voltage
      signal can effectively be held by an individual cell. The maximum number of
      cascaded cells will be limited by the effects of accumulated offset due to
      transistor mismatch, which eventually will affect the operating mode of the
      individual transistors in a cell. This latter limitation has however been dealt
      with in the topology by having an offset compensation mechanism that makes
      possible having a large number of cascaded cells and hence a long resulting
      delay. The delay line has been designed for scalp-based neural activity analysis
      that is predominantly in the sub-100 Hz frequency range. For these signals, the
      delay generated by a 31-cell cascade has been demonstrated to be programmable
      from 30 ms to 3 s. Measurement results demonstrate a 31 stage, 50 Hz bandwidth,
      0.3 s delay that operates from a 1.1 V supply with power consumption of 270 nW.

PMID- 24021655
TI  - Ion sensing (EIS) real-time quantitative monitorization of isothermal DNA
      amplification.
AB  - Field-effect-based devices are becoming a basic structural element in a new
      generation of microbiosensors. Reliable molecular characterization of DNA and/or
      RNA is of paramount importance for disease diagnostics and to follow up
      alterations in gene expression profiles. The use of such devices for point-of
      need diagnostics has been hindered by the need of standard or real-time PCR
      amplification procedures. The present work focuses on the development of a
      tantalum pentoxide (Ta2O5) based sensor for the real-time label free detection of
      DNA amplification via loop mediated isothermal amplification (LAMP) allowing for
      quantitative analysis of the cMYC proto-oncogene. The strategy based on the field
      effect sensor was tested within a range of 1 * 10(8)-10(11) copies of target DNA,
      and a linear relationship between the log copy number of the initial template DNA
      and threshold time was observed allowing for a semi-quantitative analysis of DNA
      template. The concept offers many of the advantages of isothermal quantitative
      real-time DNA amplification in a label free approach and may pave the way to
      point-of-care quantitative molecular analysis focused on ease of use and low
      cost.

PMID- 24021656
TI  - MIP-graphene-modified glassy carbon electrode for the determination of
      trimethoprim.
AB  - A novel sensitive electrochemical sensor was developed by electropolymerization
      of pyrrole (PY) and molecularly imprinted polymer (MIP) which was synthesized
      onto a glassy carbon electrode (GCE) in aqueous solution using cyclic voltammetry
      in the presence of Trimethoprim (TMP) as template molecules. Furthermore, a
      previous electrode modification was performed by deposition of a suspension of
      graphene on the electrode's surface. The performance of the imprinted and non
      imprinted (NIP) films was evaluated by impedance spectroscopy (EIS) and cyclic
      voltammetry (CV) of a ferric solution. The molecularly imprinted film exhibited a
      high selectivity and sensitivity toward TMP. The sensor presented a linear range,
      between peak current intensity and logarithm of TMP concentration between 1.0 *
      10(-6) and 1.0 * 10(-4)M. The results were accurate (with recoveries higher than
      94%), precise (with standard deviations less than 5%) and the detection limit was
      1.3 * 10(-7)M. The new sensor is selective, simple to construct and easy to
      operate. The MIP sensor was successfully applied to quantify TMP in urine
      samples.

PMID- 24021657
TI  - Sensitive and visible detection of apoptotic cells on Annexin-V modified
      substrate using aminophenylboronic acid modified gold nanoparticles (APBA-GNPs)
      labeling.
AB  - A new strategy for sensitive detection of early stage apoptosis was proposed
      based on silver-enhanced gold nanoparticle (GNP) label method. Annexin-V modified
      substrate was constructed via layer-by-layer (LBL) method for specific capture of
      early stage apoptotic Jurkat cells. A new kind of aminophenylboronic acid
      modified gold nanoparticle (APBA-GNP) was synthesized and utilized for labeling
      cells, followed by silver enhancement. Anodic stripping voltammetry (ASV) was
      applied to sensitive detection of Ag(+) dissolved from the deposited silver
      particles, which reflected the number of cells. A good linear range from 1 *
      10(2) to 3.5 * 10(3) cells was achieved, with a detection limit of 38 apoptotic
      cells. Moreover, the gray color of silver enhancement could be observed by the
      naked eye, which could be used to tell apoptotic cells apart from normal cells.
      Therefore, using the silver-enhanced GNP label method, apoptotic cells could not
      only be sensitively detected via electrochemical technique, but also can be
      discriminated from normal cells by the naked eye.

PMID- 24021658
TI  - A novel quantum dot nanocluster as versatile probe for electrochemiluminescence
      and electrochemical assays of DNA and cancer cells.
AB  - A novel dendritic quantum dot (QD) nanocluster was constructed and used as
      versatile electrochemiluminescence (ECL) and electrochemical probe for the
      detection of DNA and cancer cells. Owing to the many functional groups present in
      the nanoclusters, a large number of QDs were assembled on the nanoclusters, which
      could greatly amplify both the ECL and electrochemical signals of QDs. Carbon
      nanotubes (CNTs)/gold nanoparticles' (NPs) hybrids were used as amplified
      platform for assembling large numbers of DNA on the electrode, which also improve
      the bioactivity and stability of the electrode. After the QD-DNA signal probe was
      recognized with target DNA (t-DNA), the amplified ECL signal for the detection of
      target DNA was obtained. Furthermore, magnetic nanoparticles were employed for
      cell aptamers immobilization, the same QD nanocluster-DNA probe was also extended
      for electrochemical detection of cancer cells using sensitive anodic stripping
      voltammetry (ASV) method, which simplified the separation procedures and improved
      the sensitivity. It is anticipated that the assays could provide promising and
      cost effective approach for the early and accurate detection of DNA and cancer
      cells. 

PMID- 24021659
TI  - Paper-based chromatographic chemiluminescence chip for the detection of
      dichlorvos in vegetables.
AB  - Paper chromatography was a big breakthrough in the early of 20th century but it
      is rarely used due to the long separation time and the diffusion on the sample
      spots. In this work, for the first time, a paper-based chemiluminescence (CL)
      analytical device combined with paper chromatography was developed for the
      determination of dichlorvos (DDV) in vegetables without complicated sample
      pretreatment. The paper chromatography separation procedure can be accomplished
      in 12 min on a paper support (0.8 * 7.0 cm(2)) by using 5 uL sample spotted on
      it. After sample developing, the detection area (0.8 * 1.0 cm(2)) was cut and
      inserted between two layers of water-impermeable single-sided adhesive tapes. The
      paper-based chip was made by attaching the middle layer of paper onto the bottom
      layer. Then it was covered by another tape layer, which was patterned by the
      cutting method to form a square hole (0.8 * 1.0 cm(2)) in it. 10 MUL mixed
      solution of luminol and H2O2 was dropped on the detection area to produce CL. A
      linear relationship was obtained between the CL intensity and the concentrations
      of DDV in the range between 10.0 ng mL(-1) and 1.0 MUg mL(-1)and the detection
      limit was 3.6 ng mL(-1). Water-soluble metal ions and vitamins can be developed
      at different spatial locations relative to DDV, eliminating interference with DDV
      during detection. The paper-based chromatographic chip can be successfully used
      for the determination of DDV without complicated sample preparation in
      vegetables. This study should, therefore, be suitable for rapid and sensitive
      detection of trace levels of organophosphate pesticides in environmental and food
      samples.

PMID- 24021660
TI  - Reported gastrointestinal endoscope reprocessing lapses: the tip of the iceberg.
AB  - BACKGROUND: Most cases of microbial transmission to patients via contaminated
      endoscopes have resulted from nonadherence to reprocessing guidelines. We
      evaluated the occurrence, features, and implications of reprocessing lapses to
      gauge the nature and breadth of the problem in the context of widely available
      and accepted practice guidelines. METHODS: We examined peer-reviewed and non-peer
      reviewed literature to identify lapses reported in North America during 2005 to
      2012 resulting in patient exposure to potentially contaminated gastrointestinal
      endoscopes. RESULTS: Lapses occurred in various types of facilities and involved
      errors in all major steps of reprocessing. Each lapse continued for several
      months or years until the problem was discovered except for one that was
      described as a single incident. There were significant implications for patients,
      including notification and testing, microbial transmission, and increased
      morbidity and mortality. Only 1 reprocessing lapse was found in a peer-reviewed
      journal article, and other incidents were reported in governmental reports, legal
      documents, conference abstracts, and media reports. CONCLUSION: Reprocessing
      lapses are an ongoing and widespread problem despite the existence of guidelines.
      Lack of publication in peer-reviewed literature contributes to the perception
      that lapses are rare and inconsequential. Reporting requirements and
      epidemiologic investigations are needed to develop better evidence-based policies
      and practices.

PMID- 24021661
TI  - Unilateral thalamic deep brain stimulation in essential tremor demonstrates long
      term ipsilateral effects.
AB  - INTRODUCTION: Deep Brain Stimulation (DBS) of thalamus in essential tremor (ET)
      is effective for the treatment of contralateral tremors. Bilateral DBS controls
      tremors on both sides but is associated with increased morbidity and risks. We
      evaluated if unilateral surgery had ipsilateral benefits on tremors and thus
      could be a potentially safer alternative to bilateral DBS. METHODS: Medication
      refractory ET patients undergoing unilateral thalamic DBS were included and
      longitudinally followed. Tremor rating scale was used to record total motor, arm
      tremor and activities of daily living (ADL) scores at baseline, six months and at
      last visit (three or more years after surgery). Postoperative scores were
      recorded with DBS turned OFF and ON. RESULTS: Twenty-two patients with a mean
      follow-up 3.4 +/- 0.14 years were enrolled. When baseline scores were compared to
      scores with the DBS turned ON, significant improvements were noted in total
      tremor (40%), ADL (67%) and arm tremor scores both on the ipsilateral and the
      contralateral side at six months and at the last visit of follow-up (all p <
      0.05). Ipsilateral arm tremor (~56%) improvements were milder compared to the
      contralateral side (~73%) tremors. CONCLUSION: Unilateral thalamic DBS in ET
      demonstrates significant long-term benefits for ipsilateral arm tremors and can
      be offered to higher risk and to select patients.

PMID- 24021662
TI  - Active and passive immunization strategies based on the SDPM1 peptide demonstrate
      pre-clinical efficacy in the APPswePSEN1dE9 mouse model for Alzheimer's disease.
AB  - Recent clinical and pre-clinical studies suggest that both active and passive
      immunization strategies targeting Abeta amyloid may have clinical benefit in
      Alzheimer's disease. Here, we demonstrate that vaccination of APPswePSEN1dE9 mice
      with SDPM1, an engineered non-native Abeta amyloid-specific binding peptide,
      lowers brain Abeta amyloid plaque burden and brain Abeta1-40 and Abeta1-42
      peptide levels, improves cognitive learning and memory in Morris water maze tests
      and increases the expression of synaptic brain proteins. This was the case in
      young mice immunized prior to development of significant brain amyloid burden,
      and in older mice, where brain amyloid was already present. Active immunization
      was optimized using ALUM as an adjuvant to stimulate production of anti-SDPM1 and
      anti-Abeta amyloid antibodies. Intracerebral injection of P4D6, an SDPM1 peptide
      mimotope antibody, also lowered brain amyloid plaque burden in APPswePSEN1dE9
      mice. Additionally, P4D6 inhibited Abeta amyloid-mediated toxicity in cultured
      neuronal cells. The protein sequence of the variable domain within the P4D6 heavy
      chain was found to mimic a multimer of the SDPM1 peptide motif. These data
      demonstrate the efficacy of active and passive vaccine strategies to target Abeta
      amyloid oligomers using an engineered peptide-mimotope strategy. 

PMID- 24021663
TI  - Sentinel lymph node status in melanoma: prognostic value in a tertiary hospital
      and correlation with mitotic activity.
AB  - BACKGROUND: The prognostic value of sentinel lymph node (SLN) biopsy findings and
      mitotic activity in melanoma has been confirmed in the literature, but the
      relation between them has not been well established. OBJECTIVES: The main
      objective was to describe and analyze the correlation between SLN biopsy results
      and the mitotic rate in patients treated for melanoma in our hospital. METHODS: A
      total of 139 consecutive patients who underwent SLN biopsy between May 2001 and
      May 2009 were included. The relation between the mitotic rate and SLN status was
      analyzed with the chi(2) test and the Fischer exact test. RESULTS: The
      correlation between the 2 variables was nonsignificant (P =.071) in the patient
      series overall, but a significant association was found in the subgroup of
      patients with tumors of Breslow thickness between 1 and 4mm (P =.034). The
      likelihood (odds ratio) of SLN positivity with a mitotic rate of less than 1
      mitosis/mm2 in this subgroup was 0.838 (95% CI, 0.758-0.926). CONCLUSIONS: Our
      findings support use of the mitotic rate to predict SLN status in melanoma tumors
      of intermediate thickness. Our study also shows the need for further
      investigation of the relation between these 2 variables in thin and thick tumors.

PMID- 24021665
TI  - Allostery without conformation change: modelling protein dynamics at multiple
      scales.
AB  - The original ideas of Cooper and Dryden, that allosteric signalling can be
      induced between distant binding sites on proteins without any change in mean
      structural conformation, has proved to be a remarkably prescient insight into the
      rich structure of protein dynamics. It represents an alternative to the
      celebrated Monod-Wyman-Changeux mechanism and proposes that modulation of the
      amplitude of thermal fluctuations around a mean structure, rather than shifts in
      the structure itself, give rise to allostery in ligand binding. In a
      complementary approach to experiments on real proteins, here we take a
      theoretical route to identify the necessary structural components of this
      mechanism. By reviewing and extending an approach that moves from very coarse
      grained to more detailed models, we show that, a fundamental requirement for a
      body supporting fluctuation-induced allostery is a strongly inhomogeneous elastic
      modulus. This requirement is reflected in many real proteins, where a good
      approximation of the elastic structure maps strongly coherent domains onto rigid
      blocks connected by more flexible interface regions. 

PMID- 24021664
TI  - IL-27p28 inhibits central nervous system autoimmunity by concurrently
      antagonizing Th1 and Th17 responses.
AB  - Central nervous system (CNS) autoimmunity such as uveitis and multiple sclerosis
      is accompanied by Th1 and Th17 responses. In their corresponding animal models,
      experimental autoimmune uveitis (EAU) and experimental autoimmune
      encephalomyelitis (EAE), both responses are induced and can drive disease
      independently. Because immune responses have inherent plasticity, therapeutic
      targeting of only one pathway could promote the other, without reducing
      pathology. IL-27p28 antagonizes gp130, required for signaling by IL-27 and IL-6,
      which respectively promote Th1 and Th17 responses. We therefore examined its
      ability to protect the CNS by concurrently targeting both effector responses.
      Overexpression of IL-27p28 in vivo ameliorated EAU as well as EAE pathology and
      reduced tissue infiltration by Th1 and Th17 cells in a disease prevention, as
      well as in a disease reversal protocol. Mechanistic studies revealed inhibition
      of Th1 and Th17 commitment in vitro and decreased lineage stability of pre-formed
      effectors in vivo, with reduction in expression of gp130-dependent transcription
      factors and cytokines. Importantly, IL-27p28 inhibited polarization of human T
      cells to the Th1 and Th17 effector pathways. The ability of IL-27p28 to inhibit
      generation as well as function of pathogenic Th1 and Th17 effector cells has
      therapeutic implications for controlling immunologically complex autoimmune
      diseases. 

PMID- 24021666
TI  - The role of liquid-based preparation in the evaluation of endometrial cytology.
AB  - OBJECTIVE: Liquid-based preparation (LBP) of the endometrial lesions is an
      important diagnostic tool for a variety of endometrial abnormalities because of
      its simplicity and high quali-quantitative diagnostic yield. We aimed to
      investigate the LBP method for endometrial cytology to evaluate both benign and
      abnormal endometrial lesions. STUDY DESIGN: LBP is a semiautomated methodology
      that has recently become widely available and has gained popularity as a method
      of collecting and processing both gynecologic and nongynecologic cellular
      specimens. RESULTS: Some peculiar endometrial cytoarchitectural features were
      described using LBPs. These were advantageous to screen as compared to
      conventional slides due to a smaller screening area and an excellent quality of
      cell preparations. CONCLUSIONS: LBP is a useful tool in the cellular diagnosis
      and follow-up of endometrial abnormalities, which remains complementary to the
      emerging molecular diagnostic cytopathology. The study of LBPs from endometrial
      cytology could be challenging since it is affected by numerous look-alikes and
      diagnostic pitfalls. This review discusses these various entities and takes into
      consideration the ancillary techniques that may be useful in the diagnostic
      procedure.

PMID- 24021667
TI  - Randomized trial of two swallowing assessment approaches in patients with
      acquired brain injury: Facial-Oral Tract Therapy versus Fibreoptic Endoscopic
      Evaluation of Swallowing.
AB  - OBJECTIVE: To examine whether patients assessed for initiation of oral intake
      only by Facial-Oral Tract Therapy had a greater risk of developing aspiration
      pneumonia during neurorehabilitation than patients assessed by Fibreoptic
      Endoscopic Evaluation of Swallowing. DESIGN: Randomized controlled trial.
      SETTING: Specialized, national neurorehabilitation centre. SUBJECTS: Adult
      patients with acquired brain injury. Six hundred and seventy-nine patients were
      assessed for eligibility and 138 were randomly allocated between June 2009 and
      April 2011. INTERVENTIONS: Assessment by Facial-Oral Tract Therapy (control
      group) or Fibreoptic Endoscopic Evaluation of Swallowing (intervention group).
      MAIN MEASURE: Primary outcome was the number of aspiration pneumonias that
      developed after initiation of oral intake. RESULTS: One hundred and nineteen
      patients were included in the analysis of the primary outcome (62 controls/57
      interventions). Sixteen patients were clinically diagnosed with pneumonia (4
      controls/12 interventions). Nine patients had to be excluded: 6 patients got
      pneumonia before initiating oral intake; 3 patients with the clinical diagnosis
      of pneumonia did not show radiological signs. Seven patients were left for
      analysis, 4 of whom developed aspiration pneumonia within 10 days after
      initiating oral intake (1 control/3 interventions). CONCLUSION: In the presence
      of a structured clinical assessment with the Facial-Oral Tract Therapy approach,
      it is unnecessary to undertake an instrumental investigation of swallowing before
      initiation of oral intake.

PMID- 24021668
TI  - GATA1-mutant clones are frequent and often unsuspected in babies with Down
      syndrome: identification of a population at risk of leukemia.
AB  - Transient abnormal myelopoiesis (TAM), a preleukemic disorder unique to neonates
      with Down syndrome (DS), may transform to childhood acute myeloid leukemia (ML
      DS). Acquired GATA1 mutations are present in both TAM and ML-DS. Current
      definitions of TAM specify neither the percentage of blasts nor the role of GATA1
      mutation analysis. To define TAM, we prospectively analyzed clinical findings,
      blood counts and smears, and GATA1 mutation status in 200 DS neonates. All DS
      neonates had multiple blood count and smear abnormalities. Surprisingly, 195 of
      200 (97.5%) had circulating blasts. GATA1 mutations were detected by Sanger
      sequencing/denaturing high performance liquid chromatography (Ss/DHPLC) in 17 of
      200 (8.5%), all with blasts >10%. Furthermore low-abundance GATA1 mutant clones
      were detected by targeted next-generation resequencing (NGS) in 18 of 88 (20.4%;
      sensitivity ~0.3%) DS neonates without Ss/DHPLC-detectable GATA1 mutations. No
      clinical or hematologic features distinguished these 18 neonates. We suggest the
      term "silent TAM" for neonates with DS with GATA1 mutations detectable only by
      NGS. To identify all babies at risk of ML-DS, we suggest GATA1 mutation and blood
      count and smear analyses should be performed in DS neonates. Ss/DPHLC can be used
      for initial screening, but where GATA1 mutations are undetectable by Ss/DHPLC,
      NGS-based methods can identify neonates with small GATA1 mutant clones. 

PMID- 24021670
TI  - Applications of high-throughput DNA sequencing to benign hematology.
AB  - The development of novel technologies for high-throughput DNA sequencing is
      having a major impact on our ability to measure and define normal and pathologic
      variation in humans. This review discusses advances in DNA sequencing that have
      been applied to benign hematologic disorders, including those affecting the red
      blood cell, the neutrophil, and other white blood cell lineages. Relevant
      examples of how these approaches have been used for disease diagnosis, gene
      discovery, and studying complex traits are provided. High-throughput DNA
      sequencing technology holds significant promise for impacting clinical care. This
      includes development of improved disease detection and diagnosis, better
      understanding of disease progression and stratification of risk of disease
      specific complications, and development of improved therapeutic strategies,
      particularly patient-specific pharmacogenomics-based therapy, with monitoring of
      therapy by genomic biomarkers. 

PMID- 24021669
TI  - Massively parallel sequencing: the new frontier of hematologic genomics.
AB  - Genomic technologies are becoming a routine part of human genetic analysis. The
      exponential growth in DNA sequencing capability has brought an unprecedented
      understanding of human genetic variation and the identification of thousands of
      variants that impact human health. In this review, we describe the different
      types of DNA variation and provide an overview of existing DNA sequencing
      technologies and their applications. As genomic technologies and knowledge
      continue to advance, they will become integral in clinical practice. To
      accomplish the goal of personalized genomic medicine for patients, close
      collaborations between researchers and clinicians will be essential to develop
      and curate deep databases of genetic variation and their associated phenotypes. 

PMID- 24021672
TI  - Blood consult: paroxysmal nocturnal hemoglobinuria and its complications.

PMID- 24021671
TI  - Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia.
AB  - A subgroup of leukemogenic mixed-lineage leukemia (MLL) fusion proteins (MFPs)
      including MLL-AF9 activates the Mecom locus and exhibits extremely poor clinical
      prognosis. Mecom encodes EVI1 and MDS1-EVI1 (ME) proteins via alternative
      transcription start sites; these differ by the presence of a PRDI-BF1-RIZ1 (PR)
      domain with histone methyltransferase activity in the ME isoform. Using an ME
      deficient mouse, we show that ME is required for MLL-AF9-induced transformation
      both in vitro and in vivo. And, although Nup98-HOXA9, MEIS1-HOXA9, and E2A-Hlf
      could transform ME-deficient cells, both MLL-AF9 and MLL-ENL were ineffective,
      indicating that the ME requirement is specific to MLL fusion leukemia. Further,
      we show that the PR domain is essential for MFP-induced transformation. These
      studies clearly indicate an essential role of PR-domain protein ME in MFP
      leukemia, suggesting that ME may be a novel target for therapeutic intervention
      for this group of leukemias. 

PMID- 24021673
TI  - BLT-humanized C57BL/6 Rag2-/-gammac-/-CD47-/- mice are resistant to GVHD and
      develop B- and T-cell immunity to HIV infection.
AB  - The use of C57BL/6 Rag2(-/-)gammac(-/-) mice as recipients for
      xenotransplantation with human immune systems (humanization) has been problematic
      because C57BL/6 SIRPalpha does not recognize human CD47, and such recognition is
      required to suppress macrophage-mediated phagocytosis of transplanted human
      hematopoietic stem cells (HSCs). We show that genetic inactivation of CD47 on the
      C57BL/6 Rag2(-/-)gammac(-/-) background negates the requirement for CD47-signal
      recognition protein alpha (SIRPalpha) signaling and induces tolerance to
      transplanted human HSCs. These triple-knockout, bone marrow, liver, thymus (TKO
      BLT) humanized mice develop organized lymphoid tissues including mesenteric lymph
      nodes, splenic follicles and gut-associated lymphoid tissue that demonstrate high
      levels of multilineage hematopoiesis. Importantly, these mice have an intact
      complement system and showed no signs of graft-versus-host disease (GVHD) out to
      29 weeks after transplantation. Sustained, high-level HIV-1 infection was
      observed via either intrarectal or intraperitoneal inoculation. TKO-BLT mice
      exhibited hallmarks of human HIV infection including CD4(+) T-cell depletion,
      immune activation, and development of HIV-specific B- and T-cell responses. The
      lack of GVHD makes the TKO-BLT mouse a significantly improved model for long-term
      studies of pathogenesis, immune responses, therapeutics, and vaccines to human
      pathogens. 

PMID- 24021674
TI  - FLVCR is necessary for erythroid maturation, may contribute to platelet
      maturation, but is dispensable for normal hematopoietic stem cell function.
AB  - Heme is a pleiotropic molecule that is important for oxygen and oxidative
      metabolism, most notably as the prosthetic group of hemoglobin and cytochromes.
      Because excess free intracellular heme is toxic, organisms have developed
      mechanisms to tightly regulate its concentration. One mechanism is through active
      heme export by the group C feline leukemia virus receptor (FLVCR). Previously, we
      have shown that FLVCR is necessary for embryonic and postnatal erythropoiesis.
      However, FLVCR is also expressed in numerous other tissues, including
      hematopoietic stem cells (HSCs). To explore a possible role for FLVCR in HSC
      function, we performed serial, competitive repopulation transplant experiments
      using FLVCR-deleted and control bone marrow cells, along with wild-type
      competitor cells. Loss of FLVCR did not impact HSC function under steady-state or
      myelotoxic stress conditions (such as arsenic or radiation exposure), nor did
      FLVCR deletion result in alterations in the various progenitor compartments.
      However, even when 95% of the donor bone marrow cells lacked FLVCR, all red cells
      in recipient mice were wild type. This is due to the increased apoptosis of FLVCR
      deleted proerythroblasts. Also, remarkably, loss of FLVCR increased megakaryocyte
      ploidy. Together, these findings show FLVCR is redundant in stem cells but has
      critical and contrasting stage-specific roles in discrete hematopoietic lineages.

PMID- 24021675
TI  - The Gata1 5' region harbors distinct cis-regulatory modules that direct gene
      activation in erythroid cells and gene inactivation in HSCs.
AB  - GATA1 is a master regulator of hematopoietic differentiation, but Gata1
      expression is inactivated in hematopoietic stem cells (HSCs). Using a bacterial
      artificial chromosome containing the Gata1 gene modified with green fluorescent
      protein (GFP) reporter, we explored the function of the 3.7-kb Gata1 upstream
      region (GdC region) that harbors 3 core cis-elements: Gata1 hematopoietic
      enhancer, double GATA-motif, and CACCC-motif. Transgenic GFP expression directed
      by the Gata1-BAC faithfully recapitulated the endogenous Gata1 expression
      pattern. However, deletion of the GdC-region eliminated reporter expression in
      all hematopoietic cells. To test whether the combination of the core cis-elements
      represents the regulatory function of the GdC-region, we replaced the region with
      a 659-bp minigene that linked the three cis-elements (MG-GFP). The GFP reporter
      expression directed by the MG-GFP BAC fully recapitulated the erythroid
      megakaryocytic Gata1 expression. However, the GFP expression was aberrantly
      increased in the HSCs and was associated with decreases in DNA methylation and
      abundant GATA2 binding to the transgenic MG-GFP allele. The 3.2-kb sequences
      interspaced between the Gata1 hematopoietic enhancer and the double GATA-motif
      were able to recruit DNA methyltransferase 1, thereby exerting a cis-repressive
      function in the HSC-like cell line. These results indicate that the 3.2-kb
      interspacing sequences inactivate Gata1 by maintaining DNA-methylation in the
      HSCs. 

PMID- 24021676
TI  - Burkitt lymphoma in pregnancy: two cases of successful treatment and continued
      fertility; with a review of the literature.

PMID- 24021678
TI  - Fondaparinux as an alternative to vitamin K antagonists in haemodialysis
      patients.
AB  - BACKGROUND: Accelerated vascular calcification and increased risk of
      calciphylaxis can be a reason to restrict the use of vitamin K antagonists in
      dialysis patients. We describe the use of fondaparinux, a prototype indirect
      factor Xa inhibitor, as an alternative anticoagulant to coumarin derivatives in
      dialysis patients. METHODS: In this case series, we included six chronic
      haemodialysis patients treated with vitamin K antagonists. Low-molecular-weight
      heparin given as anticoagulant during dialysis was replaced by fondaparinux. Anti
      Xa activity was regularly measured pre- and postdialysis to adapt the dose of
      fondaparinux. Adequate continuous anticoagulation and circuit patency were
      registered by evaluating clotting in the bubble trap and dialyser membrane at the
      end of dialysis. RESULTS: Anticoagulation with fondaparinux at a starting dose of
      2.5 mg resulted in an effective anticoagulation in the majority of dialysis
      sessions. Although median predialysis anti-Xa levels were significantly lower
      [0.36 IU/mL (0.30-0.42 IU/mL) (P < 0.0001)] than postdialysis levels [0.75 IU/mL
      (0.65-0.80 IU/mL)], predialysis anti-Xa levels were sufficient to limit the risk
      of thromboembolism. After an initial period of gradually increasing anti-Xa
      levels due to accumulation of fondaparinux, stable levels were achieved.
      Haemodialysis without clotting problems was possible in 96% of the sessions
      (clotting score <=1), whereas two episodes (2/459 dialysis sessions) of major
      clotting were observed, defined as clotting of the extracorporeal circuit
      necessitating premature termination of the procedure. CONCLUSIONS: We
      demonstrated that fondaparinux is a valuable anticoagulant for patients dialysed
      with low-flux membranes in need of continuous anticoagulation.

PMID- 24021677
TI  - Postconditioning ameliorates mitochondrial DNA damage and deletion after renal
      ischemic injury.
AB  - BACKGROUND: Reactive oxygen species (ROS) play a major role in causing injury in
      ischemia-reperfusion (I/R). Mitochondrial DNA (mtDNA) is particularly vulnerable
      to oxidative damage. We propose that increased mitochondrial ROS production is
      likely to damage mtDNA, causing further injury to mitochondria, and
      postconditioning (POC) may ameliorate kidney I/R injury by mitigating
      mitochondrial damage. METHODS: Rats were divided into seven groups: (i) Sham
      operated animals with an unconstricted renal artery; (ii) Sham + 5
      hydroxydecanoate (5-HD); (iii) I/R; (iv) I/R + 5-HD; (v) POC; (vi) Sham POC and
      (vii) POC + 5-HD. Renal injury, oxidative DNA damage, mtDNA deletions,
      mitochondrial membrane potential (MMP) and expression of the ATP-sensitive K(+)
      (KATP) channel subunit Kir6.2 were evaluated. RESULTS: Following 1 h of
      reperfusion, animals in the I/R group exhibited increased ROS, oxidative mtDNA
      damage shown by 8-hydroxy-2-deoxyguanosine staining, multiple base pair deletions
      and decreased MMP. However, POC rats exhibited less ROS, oxidative mtDNA damage
      and deletions and improved MMP. After 2 days of reperfusion, serum creatinine was
      elevated in I/R rats and the number of TdT-mediated dUTP nick-end labeled
      positive tubular cells was increased and was associated with activation of
      caspase-3. Therefore, POC prevented the deleterious effects of I/R injury.
      Furthermore, the expression of mitochondrial Kir6.2 was widely distributed in
      renal tubular epithelial cells in Sham and POC rats and was lower in I/R rats.
      All of the protective effects of POC were reversed by the K(+) (KATP) channel
      blocker 5-HD. CONCLUSION: POC may attenuate I/R injury by reducing mitochondrial
      oxidative stress and mtDNA damage and sustaining MMP.

PMID- 24021679
TI  - The Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study protocol.
AB  - BACKGROUND AND PURPOSE: Epidemiological studies of intracerebral hemorrhage (ICH)
      have consistently demonstrated variation in incidence, location, age at
      presentation, and outcomes among non-Hispanic white, black, and Hispanic
      populations. We report here the design and methods for this large, prospective,
      multi-center case-control study of ICH. METHODS: The Ethnic/Racial Variations of
      Intracerebral Hemorrhage (ERICH) study is a multi-center, prospective case
      control study of ICH. Cases are identified by hot-pursuit and enrolled using
      standard phenotype and risk factor information and include neuroimaging and blood
      sample collection. Controls are centrally identified by random digit dialing to
      match cases by age (+/-5 years), race, ethnicity, sex, and metropolitan region.
      RESULTS: As of March 22, 2013, 1655 cases of ICH had been recruited into the
      study, which is 101.5% of the target for that date, and 851 controls had been
      recruited, which is 67.2% of the target for that date (1267 controls) for a total
      of 2506 subjects, which is 86.5% of the target for that date (2897 subjects). Of
      the 1655 cases enrolled, 1640 cases had the case interview entered into the
      database, of which 628 (38%) were non-Hispanic black, 458 (28%) were non-Hispanic
      white, and 554 (34%) were Hispanic. Of the 1197 cases with imaging submitted, 876
      (73.2%) had a 24 hour follow-up CT available. In addition to CT imaging, 607
      cases have had MRI evaluation. CONCLUSIONS: The ERICH study is a large, case
      control study of ICH with particular emphasis on recruitment of minority
      populations for the identification of genetic and epidemiological risk factors
      for ICH and outcomes after ICH.

PMID- 24021680
TI  - Novel approaches to neuroprotection trials in acute ischemic stroke.

PMID- 24021681
TI  - Toward solutions for minimizing disparities in stroke: National Institute of
      Neurological Disorders and Stroke update.

PMID- 24021682
TI  - Characteristics and outcomes among patients transferred to a regional
      comprehensive stroke center for tertiary care.
AB  - BACKGROUND AND PURPOSE: Many patients are transferred to comprehensive stroke
      centers for advanced acute ischemic stroke care, especially after intravenous
      tissue plasminogen activator. We sought to determine differences in the baseline
      characteristics and outcomes between patients with acute ischemic stroke
      presenting directly to our academic stroke center's front door versus transfers
      in from another acute care hospital. METHODS: Using our institutional Get With
      The Guidelines (GWTG)-Stroke registry, we analyzed all 3660 consecutively
      admitted patients with acute ischemic stroke (January 2005-June 2012). Univariate
      and multivariable models explored differences in front door versus transfer-in
      patients. RESULTS: Fifty percent of all patients with acute ischemic stroke were
      transfer-in. Compared with front door patients, transfer-in were younger (67+/-16
      versus 71+/-15 years; P<0.001), had worse median initial National Institutes of
      Health Stroke Scale score (7.0 versus 4.0; P<0.001), more often had limb weakness
      (35% versus 27%; P<0.001) or aphasia (16% versus 11%; P<0.001), and received
      intravenous tissue plasminogen activator (29% versus 13%; P<0.001). Despite a
      trend toward higher in-hospital mortality in transfer-in patients, the difference
      was not statistically significant (13% versus 11%; P=0.08) between the 2 groups.
      Transfer-in patients had a longer hospital length of stay (5 versus 4 days;
      P<0.001) and were more often discharged to inpatient rehabilitation (48% versus
      34%; P<0.001). Independent predictors of in-hospital mortality were increasing
      age (odds ratio [OR], 1.38 per decade [1.23-1.55]; P<0.001), atrial fibrillation
      (OR, 1.47 [1.12-1.93]; P=0.006), coronary artery disease (OR, 2.02 [1.53-2.67];
      P<0.001), and initial National Institutes of Health Stroke Scale (OR, 1.20 per
      point [1.18-1.23]; P<0.001). Transfer status was not independently associated
      with in-hospital mortality (OR, 0.99 [0.76-1.29]; P=0.928). CONCLUSIONS: Despite
      having more severe strokes on arrival at our hospital, transfer-in patients had
      similar in-hospital mortality versus front door patients and were more likely to
      be discharged to rehabilitation. These outcomes lend support to the concept of
      regionalized stroke care and concentrating patients who are more disabled at more
      advanced stroke care centers.

PMID- 24021683
TI  - Switching strategy for mechanical thrombectomy of acute large vessel occlusion in
      the anterior circulation.
AB  - BACKGROUND AND PURPOSE: We introduce the concept of a switching strategy for
      mechanical thrombectomy with period-to-period analysis. In period 1, forced
      arterial suction thrombectomy with a Penumbra reperfusion catheter was performed,
      even in difficult cases; in period 2, forced arterial suction thrombectomy was
      initially performed, with switching to Solitaire in difficult cases. METHODS: We
      analyzed 135 consecutive patients treated with mechanical thrombectomy with acute
      large vessel occlusion in the anterior circulation, 61 from period 1 and 74 from
      period 2. We defined difficult case for both periods as >=3 failed attempts at
      recanalization. RESULTS: Period 2 showed a trend for better angiographic outcome
      of Thrombolysis in Cerebral Infarction 2b-3 (73.8%, period 1 versus 85.1%, period
      2; P=0.10). In interperiod subgroup analysis of difficult cases, switching
      significantly outperformed nonswitching in Thrombolysis in Cerebral Infarction 2b
      3 recanalization (52.7% versus 82.9%; P=0.030). Differences in puncture-to
      recanalization time, symptomatic intracranial hemorrhage incidence, and procedure
      related complications were not statistically significant. CONCLUSIONS: A
      switching strategy using 2 mechanical thrombectomy techniques (forced arterial
      suction thrombectomy to Solitaire) may harbor better angiographic outcomes than a
      1 technique only strategy (forced arterial suction thrombectomy).

PMID- 24021685
TI  - The Stroke Genetics Network: living up to its potential.

PMID- 24021686
TI  - Serum alkaline phosphatase and phosphate in cerebral atherosclerosis and
      functional outcomes after cerebral infarction.
AB  - BACKGROUND AND PURPOSE: Higher serum alkaline phosphatase (ALP) and phosphate
      levels are associated with atherosclerotic disease and an increased risk of
      cardiovascular events. However, the association of ALP/phosphate with cerebral
      atherosclerosis and prognosis in patients with acute stroke is not well known.
      METHODS: In 1034 patients with first-ever acute cerebral infarction, levels of
      ALP and phosphate were compared with (1) cerebral atherosclerosis and (2) poor
      long-term functional outcomes as defined by the modified Rankin Scale>2 at 3
      months after stroke onset. RESULTS: ALP levels were not associated with cerebral
      atherosclerosis. However, higher levels of ALP were associated with a poor
      functional outcome (adjusted odds ratio per 1 SD, 1.25; 95% confidence interval,
      1.04-1.50). Phosphate was associated with neither cerebral atherosclerosis nor
      functional outcome. CONCLUSIONS: A higher level of ALP was not associated with
      cerebral atherosclerosis but was an independent prognostic factor for long-term
      functional outcome after acute cerebral infarction.

PMID- 24021684
TI  - Stroke Genetics Network (SiGN) study: design and rationale for a genome-wide
      association study of ischemic stroke subtypes.
AB  - BACKGROUND AND PURPOSE: Meta-analyses of extant genome-wide data illustrate the
      need to focus on subtypes of ischemic stroke for gene discovery. The National
      Institute of Neurological Disorders and Stroke SiGN (Stroke Genetics Network)
      contributes substantially to meta-analyses that focus on specific subtypes of
      stroke. METHODS: The National Institute of Neurological Disorders and Stroke SiGN
      includes ischemic stroke cases from 24 genetic research centers: 13 from the
      United States and 11 from Europe. Investigators harmonize ischemic stroke
      phenotyping using the Web-based causative classification of stroke system, with
      data entered by trained and certified adjudicators at participating genetic
      research centers. Through the Center for Inherited Diseases Research, the Network
      plans to genotype 10,296 carefully phenotyped stroke cases using genome-wide
      single nucleotide polymorphism arrays and adds to these another 4253 previously
      genotyped cases, for a total of 14,549 cases. To maximize power for subtype
      analyses, the study allocates genotyping resources almost exclusively to cases.
      Publicly available studies provide most of the control genotypes. Center for
      Inherited Diseases Research-generated genotypes and corresponding phenotypes will
      be shared with the scientific community through the US National Center for
      Biotechnology Information database of Genotypes and Phenotypes, and brain MRI
      studies will be centrally archived. CONCLUSIONS: The Stroke Genetics Network,
      with its emphasis on careful and standardized phenotyping of ischemic stroke and
      stroke subtypes, provides an unprecedented opportunity to uncover genetic
      determinants of ischemic stroke.

PMID- 24021687
TI  - Prospective validation of the computed tomographic angiography spot sign score
      for intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) results in high mortality
      and morbidity for patients. Previous retrospective studies correlated the spot
      sign score (SSSc) with ICH expansion, mortality, and clinical outcome among ICH
      survivors. We performed a prospective study to validate the SSSc for the
      prediction of ICH expansion, mortality, and clinical outcome among survivors.
      METHODS: We prospectively included consecutive patients with primary ICH
      presenting to a single institution for a 1.5-year period. All patients underwent
      baseline noncontrast computed tomography (CT) and multidetector CT angiography
      performed within 24 hours of admission and a follow-up noncontrast CT within 48
      hours after the initial CT. The ICH volume was calculated on the noncontrast CT
      images using semiautomated software. The SSSc was calculated on the multidetector
      CT angiographic source images. We assessed in-hospital mortality and modified
      Rankin Scale at discharge and at 3 months among survivors. A multivariate
      logistic regression analysis was performed to determine independent predictors of
      hematoma expansion, in-hospital mortality, and poor clinical outcome. RESULTS: A
      total of 131 patients met the inclusion criteria. Of the 131 patients, a spot
      sign was detected in 31 patients (24%). In a multivariate analysis, the SSSc
      predicted significant hematoma expansion (odds ratio, 3.1; 95% confidence
      interval, 1.77-5.39; P<=0.0001), in-hospital mortality (odds ratio, 4.1; 95%
      confidence interval, 2.11-7.94; P<=0.0001), and poor clinical outcome (odds
      ratio, 3; 95% confidence interval, 1.4-4.42; P=0.004). In addition, the SSSc was
      an accurate grading scale for ICH expansion, modified Rankin Scale at discharge,
      and in-hospital mortality. CONCLUSIONS: The SSSc demonstrated a strong stepwise
      correlation with hematoma expansion and clinical outcome in patients with primary
      ICH.

PMID- 24021688
TI  - Population-based case-control study of white matter changes on brain imaging in
      transient ischemic attack and ischemic stroke.
AB  - BACKGROUND AND PURPOSE: White matter changes (WMC) are a common finding on brain
      imaging and are associated with an increased risk of ischemic stroke. They are
      most frequent in small vessel stroke; however, in the absence of comparisons with
      normal controls, it is uncertain whether WMC are also more frequent than expected
      in other stroke subtypes. Therefore, we compared WMC in pathogenic subtypes of
      ischemic stroke versus controls in a population-based study. METHODS: We
      evaluated the presence and severity of WMC on computed tomography and on magnetic
      resonance brain imaging using modified Blennow/Fazekas scale and age-related
      white matter changes scale, respectively, in a population-based study of patients
      with incident transient ischemic attack or ischemic stroke (Oxford Vascular
      Study) and in a study of local controls (Oxford Project to Investigate Memory and
      Ageing) without history of transient ischemic attack or ischemic stroke, with
      stratification by stroke pathogenesis (Trial of Org10172 in Acute Stroke
      Treatment classification). RESULTS: Among 1601 consecutive eligible patients with
      first-ever ischemic events, 1453 patients had computed tomography brain imaging,
      562 had magnetic resonance imaging, and 414 patients had both. Compared with 313
      controls (all with computed tomography and 131 with magnetic resonance imaging)
      and after adjustment for age, sex, diabetes mellitus, and hypertension,
      moderate/severe WMC (age-related white matter changes scale) were more frequent
      in patients with small vessel events (odds ratio, 3.51 [95% confidence interval,
      2.13-5.76]; P<0.0001) but not in large artery (odds ratio, 1.03 [95% confidence
      interval, 0.64-1.67]), cardioembolic (odds ratio, 0.87 [95% confidence interval,
      0.56-1.34]), or undetermined (odds ratio, 0.90 [95% confidence interval, 0.62
      1.30]) subtypes. Results were consistent for ischemic stroke and transient
      ischemic attack, for other scales, and for magnetic resonance imaging and
      computed tomography separately. CONCLUSIONS: In contrast to small vessel ischemic
      events, WMC were not independently associated with other pathogenic subtypes,
      suggesting that WMC are unlikely to be an independent risk factor for nonsmall
      vessel events.

PMID- 24021689
TI  - Expression of FoxO3a in clinical cases of malignant lymphoma.
AB  - Cancer-initiating cells (CICs) are a limited number of cells with tumorigenic
      activity. Few studies have been performed on CICs in malignant lymphoma. We
      recently demonstrated that a small number of FoxO3a-expressing cells possessed
      CIC-like potential in Hodgkin's lymphoma (HL) cell lines. In the present study,
      FoxO3a expression was examined immunohistochemically in 137 patients with
      malignant lymphoma. Among patients with HL, FoxO3a-positive tumor cells were
      detected in 11 of 11 with nodular sclerosis classical HL, 8 of 15 with mixed
      cellularity classical HL, 0 of 1 with lymphocyte-rich classical HL, and 2 of 3
      with nodular lymphocyte-predominant HL. Only limited numbers of patients with non
      HL expressed FoxO3a: 4 of 66 with diffuse large B-cell lymphoma, 1 of 20 with
      follicular lymphoma, and 1 of 5 with peripheral T-cell lymphoma, not otherwise
      specified. No FoxO3a expression was detected in patients with mantle cell
      lymphoma (n=3), extranodal marginal zone B-cell lymphoma (n=3), mediastinal large
      B-cell lymphoma (n=1), NK/T cell lymphoma (n=5), anaplastic large cell lymphoma
      (n=2), or T-lymphoblastic lymphoma/leukemia (n=2). These results suggest that
      FoxO3a is expressed mostly in patients with HL, but not in patients with non-HL.
      FoxO3a expression was limited to a small number of Hodgkin cells in a quiescent
      state. FoxO3a may be a CIC marker of HL, but not of non-HL. 

PMID- 24021690
TI  - Grant applications with a result-based orientation.

PMID- 24021691
TI  - How to define a poor outcome after transcatheter aortic valve replacement:
      conceptual framework and empirical observations from the placement of aortic
      transcatheter valve (PARTNER) trial.
AB  - BACKGROUND: Transcatheter aortic valve replacement (TAVR) has emerged as a less
      invasive option for valve replacement of patients with severe aortic stenosis.
      Although it has been recommended that TAVR should not be offered to patients who
      will not improve functionally or derive meaningful survival benefit from the
      procedure, no guidance exists on how best to identify such patients. The first
      step in this process is to define a poor outcome that can then be used as a
      foundation for subsequent case identification. We sought to evaluate potential
      definitions of a poor outcome after TAVR that combine both mortality and quality
      of life components. METHODS AND RESULTS: Using data from 463 patients who
      underwent TAVR as part of the Placement of AoRTic TraNscathetER Valve (PARTNER)
      trial, we evaluated 6-month mortality and quality of life outcomes using the
      Kansas City Cardiomyopathy Questionnaire to explore potential definitions of a
      poor outcome. We then compared the strengths and weaknesses of each potential
      definition by examining the relationship between baseline and 6-month Kansas City
      Cardiomyopathy Questionnaire scores for each patient. Based on these analyses, we
      argue that the most appropriate definition of a poor outcome after TAVR is (1)
      death, (2) Kansas City Cardiomyopathy Questionnaire overall summary score <45, or
      (3) Kansas City Cardiomyopathy Questionnaire decrease of >=10 points, which best
      reflects a failure to achieve the therapeutic goals of TAVR. CONCLUSIONS: Using
      empirical data on a large number of patients enrolled in the PARTNER trial, we
      propose a definition for poor outcome after TAVR that combines both mortality and
      quality of life measures into a single composite end point. Use of this end point
      (or other similar end points) in future studies can facilitate development of
      predictive models that may be useful to identify patients who are poor candidates
      for TAVR and to provide such patients and their families with appropriate
      expectations of functional recovery after TAVR.

PMID- 24021692
TI  - Propensity score methods for confounding control in nonexperimental research.

PMID- 24021694
TI  - Exercise mediates the association between positive affect and 5-year mortality in
      patients with ischemic heart disease.
AB  - BACKGROUND: Positive affect has been associated with better prognosis in patients
      with ischemic heart disease, but the underlying mechanisms remain unclear. We
      examined whether positive affect predicted time to first cardiac-related
      hospitalization and all-cause mortality, and whether exercise mediated this
      relationship in patients with established ischemic heart disease. METHODS AND
      RESULTS: The sample comprised 607 patients with ischemic heart disease from
      Holbaek Hospital, Denmark. In 2005, patients completed the Global Mood Scale
      (GMS) to assess positive affect and a purpose-designed question on exercise. Data
      on mortality and hospitalization were collected from Danish national registers
      for the period 2006-2010. Adjusted Cox and logistic regression were used to
      analyze the mediation model. Because no significant association between positive
      affect and cardiac-related hospitalization was found, we constructed no mediation
      model for hospitalization. Importantly, patients with high positive affect had a
      significantly reduced risk of all-cause mortality (hazard ratio, 0.58; 95%
      confidence interval, 0.37-0.92; unadjusted analysis) and were more likely to
      exercise (odds ratio, 1.99; 95% confidence interval, 1.44-2.76; unadjusted
      analysis; odds ratio, 1.48; 95% confidence interval, 1.03-2.13; adjusted
      analysis). When controlling for positive affect and other relevant variables,
      patients engaged in exercise were less likely to die during follow-up (hazard
      ratio, 0.50; 95% confidence interval, 0.31-0.80; P=0.004). Importantly, exercise
      acted as a mediator in the relationship between positive affect and mortality.
      CONCLUSIONS: Patients with higher levels of positive affect were more likely to
      exercise and had a lower risk of dying during 5-year follow-up, with exercise
      mediating the relationship between positive affect and mortality. Interventions
      aimed at increasing both positive affect and exercise may have better results
      with respect to patients' prognosis and psychological well-being than
      interventions focusing on 1 of these factors alone.

PMID- 24021693
TI  - Cost and resource utilization associated with use of computed tomography to
      evaluate chest pain in the emergency department: the Rule Out Myocardial
      Infarction using Computer Assisted Tomography (ROMICAT) study.
AB  - BACKGROUND: Coronary computed tomographic angiography (cCTA) allows rapid,
      noninvasive exclusion of obstructive coronary artery disease (CAD). However,
      concern exists whether implementation of cCTA in the assessment of patients
      presenting to the emergency department with acute chest pain will lead to
      increased downstream testing and costs compared with alternative strategies. Our
      aim was to compare observed actual costs of usual care (UC) with projected costs
      of a strategy including early cCTA in the evaluation of patients with acute chest
      pain in the Rule Out Myocardial Infarction Using Computer Assisted Tomography I
      (ROMICAT I) study. METHODS AND RESULTS: We compared cost and hospital length of
      stay of UC observed among 368 patients enrolled in the ROMICAT I study with
      projected costs of management based on cCTA. Costs of UC were determined by an
      electronic cost accounting system. Notably, UC was not influenced by cCTA results
      because patients and caregivers were blinded to the cCTA results. Costs after
      early implementation of cCTA were estimated assuming changes in management based
      on cCTA findings of the presence and severity of CAD. Sensitivity analysis was
      used to test the influence of key variables on both outcomes and costs. We
      determined that in comparison with UC, cCTA-guided triage, whereby patients with
      no CAD are discharged, could reduce total hospital costs by 23% (P<0.001).
      However, when the prevalence of obstructive CAD increases, index hospitalization
      cost increases such that when the prevalence of >= 50% stenosis is >28% to 33%,
      the use of cCTA becomes more costly than UC. CONCLUSIONS: cCTA may be a cost
      saving tool in acute chest pain populations that have a prevalence of potentially
      obstructive CAD <30%. However, increased cost would be anticipated in populations
      with higher prevalence of disease.

PMID- 24021696
TI  - Digitalis, yesterday and today, but not forever.

PMID- 24021698
TI  - Can advanced healthcare technology save money?

PMID- 24021697
TI  - Effectiveness and safety of digoxin among contemporary adults with incident
      systolic heart failure.
AB  - BACKGROUND: Clinical guidelines recommend digoxin for patients with symptomatic
      systolic heart failure (HF) receiving optimal medical therapy, but this
      recommendation is based on limited, older trial data. We evaluated the
      effectiveness and safety of digoxin in a contemporary cohort of patients with
      incident systolic HF. METHODS AND RESULTS: We identified adults with incident
      systolic HF between 2006 and 2008 within Kaiser Permanente Northern California
      who had no prior digoxin use. We used multivariable extended Cox regression to
      examine the association between new digoxin use and risks of death and HF
      hospitalization, controlling for medical history, laboratory results,
      medications, HF disease severity, and the propensity for digoxin use. We also
      conducted analyses stratified by sex and concurrent beta-blocker use. Among 2891
      newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a
      median 2.5 years of follow-up, incident digoxin use was associated with higher
      rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization
      (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident
      digoxin use was associated with higher mortality (hazard ratio, 1.72; 95%
      confidence interval, 1.25-2.36) but no significant difference in the risk of HF
      hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82-1.34). Results
      were similar in analyses stratified by sex and beta-blocker use. CONCLUSIONS:
      Digoxin use in patients with incident systolic HF was independently associated
      with a higher risk of death but no difference in HF hospitalization.

PMID- 24021700
TI  - Practical implementation of the coronary revascularization heart team.

PMID- 24021701
TI  - Facial reactions during emotion recognition in borderline personality disorder: a
      facial electromyography study.
AB  - BACKGROUND: Previous studies have suggested increased sensitivity for emotional
      facial expressions and subtle impairments in emotion recognition from facial
      expressions in borderline personality disorder (BPD). It has been proposed that
      facial mimicry contributes to emotion recognition of and emotional response to
      facial expressions. This study investigated whether BPD patients differ in facial
      reactions, emotion recognition and their subjective emotional response to faces
      showing different emotional expressions. METHOD: Twenty-eight female BPD patients
      and 28 healthy controls underwent a facial recognition task with dynamic facial
      pictures while facial muscle activity (occipitofrontalis, corrugator supercilii,
      levator labii superioris, zygomaticus major and orbicularis oculi) was recorded.
      Furthermore, participants rated the emotional intensity of the presented faces
      and the intensity of their subjective feeling of this emotion. RESULTS: Compared
      to controls, BPD patients showed enhanced responses of the corrugator supercilii
      muscle in response to angry, sad and disgusted facial expressions, and attenuated
      responses of the levator labii superioris in response to happy and surprised
      faces. There were no overall group differences regarding emotion recognition
      performance or intensity ratings. CONCLUSION: These results do not support the
      view that facial recognition in BPD is impaired or that there is a general
      hypersensitivity to the emotional state of others. Instead, they suggest a
      negativity bias in BPD, expressed by reduced facial responding to positive social
      signals and increased facial responding to negative social signals. This is a
      pattern of facial reactions that might contribute to the difficulties in social
      interactions frequently reported by patients with this disorder.

PMID- 24021699
TI  - Barriers and facilitators to learning and performing cardiopulmonary
      resuscitation in neighborhoods with low bystander cardiopulmonary resuscitation
      prevalence and high rates of cardiac arrest in Columbus, OH.
AB  - BACKGROUND: Residents who live in neighborhoods that are primarily black, Latino,
      or poor are more likely to have an out-of-hospital cardiac arrest, less likely to
      receive cardiopulmonary resuscitation (CPR), and less likely to survive. No prior
      studies have been conducted to understand the contributing factors that may
      decrease the likelihood of residents learning and performing CPR in these
      neighborhoods. The goal of this study was to identify barriers and facilitators
      to learning and performing CPR in 3 low-income, high-risk, and predominantly
      black neighborhoods in Columbus, OH. METHODS AND RESULTS: Community-Based
      Participatory Research approaches were used to develop and conduct 6 focus groups
      in conjunction with community partners in 3 target high-risk neighborhoods in
      Columbus, OH, in January to February 2011. Snowball and purposeful sampling, done
      by community liaisons, was used to recruit participants. Three reviewers analyzed
      the data in an iterative process to identify recurrent and unifying themes. Three
      major barriers to learning CPR were identified and included financial,
      informational, and motivational factors. Four major barriers were identified for
      performing CPR and included fear of legal consequences, emotional issues,
      knowledge, and situational concerns. Participants suggested that family/self
      preservation, emotional, and economic factors may serve as potential facilitators
      in increasing the provision of bystander CPR. CONCLUSIONS: The financial cost of
      CPR training, lack of information, and the fear of risking one's own life must be
      addressed when designing a community-based CPR educational program. Using data
      from the community can facilitate improved design and implementation of CPR
      programs.

PMID- 24021702
TI  - [Response to "complete atrioventricular block secondary to radiotherapy: role of
      accessory pathways"].

PMID- 24021704
TI  - Increased IL10 plasmatic levels in Fanconi anemia patients.
AB  - Fanconi anemia (FA) is a rare disease, autosomal recessive and X linked, which is
      clinically prone to development of hematological abnormalities and neoplasms,
      especially acute myeloid leukemia. In this work IL-10 and TGF-beta levels were
      measured on FA patients' plasma since they are the regulatory cytokines of TNF
      alpha and INF-gamma which had been described to be overexpressed in this genetic
      disease. Our results show increased IL-10 plasma levels in 25% of FA patients
      studied, but levels of TGF-beta within the normal range. TNF-alpha and INF-gamma
      were also measured and found to be increased in 24% and 23% of FA patients,
      respectively. However, no inverse correlation was observed between augmented
      levels of IL-10 and TNF or IFN-gamma. Patients with elevated levels of TNF-alpha
      and INF-gamma presented bone marrow hypocellularity. IL-10 levels did not appear
      to be determinant for bone marrow cellularity. These data suggest that IL-10 is
      also a feature of Fanconi anemia pathophysiology. 

PMID- 24021703
TI  - [Pharmaconutrition with parenteral selenium in sepsis].
AB  - Critical illness is characterized by oxidative stress which leads to multiple
      organ failure, and sepsis-related organ dysfunction remains the most common cause
      of death in the intensive care unit. Over the last 2 decades, different
      antioxidant therapies have been developed to improve outcomes in septic patients.
      According to recent evidence, selenium therapy should be considered the
      cornerstone of the antioxidant strategies. Selenium given as selenious acid or
      sodium selenite should be considered as a drug or pharmaconutrient with
      prooxidant and cytotoxic effects when a loading dose in intravenous bolus form is
      administered, particularly in the early stage of severe sepsis/septic shock. To
      date, several phase ii trials have demonstrated that selenium therapy may be able
      to decrease mortality, improve organ dysfunction and reduce infections in
      critically ill septic patients. The effect of selenium therapy in sepsis syndrome
      must be confirmed by large, well designed phase iii clinical trials. The purpose
      of this review is to discuss current evidence on selenium pharmaconutrition in
      sepsis syndrome. 

PMID- 24021705
TI  - Comparison of the immune microenvironment of the oral cavity and cervix in
      healthy women.
AB  - BACKGROUND: Despite similar frequencies of exposure, the low prevalence of
      certain sexually transmitted infections such as Chlamydia, HPV and HIV-1 in the
      oral cavity relative to the cervix is poorly understood. This could be explained
      in part by differences in host immune microenvironments between these two
      anatomic sites. OBJECTIVE: We compared the concentration and correlation of 27
      different immune markers in paired secretion specimens collected from the oral
      and cervical mucosa of healthy women. METHODS: Paired oral and cervical secretion
      specimens were collected from thirty-nine women. The concentration of twenty
      seven different immune markers was estimated using a Luminex multiplex assay.
      Marker concentration was normalized to total protein present in the specimen.
      Median immune marker concentrations were compared across anatomic sites.
      Unsupervised hierarchical clustering analysis was utilized to identify groups of
      markers that shared similar patterns of relative concentrations across anatomic
      sites. RESULTS: The oral cavity had significantly higher concentrations of
      eotaxin, IFN-gamma, IL-2, IL-4, IL-5, IL-7, IL-9, IL-13, IL-15, PDGF-BB, TNF
      alpha, (p<0.01 for each) while the cervix had higher concentrations of pro
      inflammatory markers such as FGF-basic, IL-1ra, IL-1beta, IL-6, IL-8, IP-10, G
      CSF, GM-CSF, MCP-1, MIP-1beta, VEGF (p<0.01 for each). Hierarchical cluster
      analysis identified two groups of immune markers comprised of T-cell related
      immune markers with significantly higher concentrations in the oral cavity
      relative to the cervix, and a third cluster consisting of mostly inflammatory
      immune markers which were higher concentrations in the cervix. The oral cavity
      had a larger number of significant inter-marker correlations as compared to the
      cervix. CONCLUSIONS: The oral cavity and cervix have significantly different
      immune marker profiles, which may in part explain the significantly lower burden
      of sexually transmitted infections such as Chlamydia, HPV, and HIV-1 in the oral
      cavity vs. the cervix.

PMID- 24021706
TI  - Deficiency of alpha-calcitonin gene-related peptide induces inflammatory
      responses and lethality in sepsis.
AB  - In the present study, we examined the role of alpha-calcitonin gene-related
      peptide (alphaCGRP) on expression of neuropeptides in the brain, inflammatory
      responses, and survival rate in septic shock condition. We examined expression of
      neuropeptides such as alphaCGRP, proopiomelanocortin (POMC), corticotrophin
      releasing hormone (CRH), and proenkephalin (ProENK) in the hippocampus and
      hypothalamus in C57BL/6 (WT) or alphaCGRP-/- (KO) mice subjected to sepsis. Cecal
      ligation and puncture (CLP) or lipopolysaccharide/D-galactosamine (LPS/D-GalN)
      treatment showed significant increases of hippocampal and hypothalamic alphaCGRP,
      POMC, CRH, and ProENK mRNA levels in WT mice, but not ProENK mRNA in the
      hypothalamus at 6h after on-set of sepsis. However, enhanced mRNA levels of POMC,
      CRH, and ProENK genes were not increased in the hippocampus and hypothalamus of
      CLP-subjected KO mice at 6h following sepsis. KO mice treated with LPS/D-GalN
      displayed a significant enhancement of plasma corticosterone, aspartate
      aminotransferase, and alanine aminotransferase levels compared to LPS/D-GalN
      treated WT mice at 12h after induction of sepsis. In addition, plasma levels of
      pro-inflammatory cytokines, such as IL-1beta and TNF-alpha, were also further
      increased in KO mice compared to WT mice at 24h after CLP or LPS/D-GalN
      treatment. Interestingly, mRNA expressions of IL-6 and IL-10, anti-inflammatory
      cytokines, were synergistically enhanced in liver and lymph node of KO mice
      compared to WT mice at 6h after CLP. However, plasma level of IL-10 but not IL-6
      was significantly decreased in KO mice compared to WT mice at 24h after CLP or
      LPS/D-GalN challenge. The survival rate of KO mice was significantly reduced
      compared to WT mice following mild (1 punch) and moderate (2 punch) CLP and LPS/D
      GalN administration. Taken together, our findings suggest that the activation of
      alphaCGRP may induce other neuropeptides associated with immunomodulation at CNS
      level and modulate immune responses as enhancing anti-inflammatory cytokines and
      reducing pro-inflammatory cytokines during the sepsis. 

PMID- 24021708
TI  - Biologics in relapsing polychondritis: a case series.
AB  - OBJECTIVES: To describe the effects of biologics in an unbiased series of
      relapsing polychondritis cases. METHODS: We extracted all the cases encoded
      'polychondritis' from the computerized medical files of our department. The
      relapsing polychondritis diagnosis was confirmed using Damiani's criteria.
      Patients treated with biologics were evaluated for efficacy and adverse drugs
      reactions until October 2012. RESULTS: Nine patients were exposed to 22 biologics
      as corticosteroid-sparing drugs. Biologics were used at the same doses as in
      rheumatoid arthritis. Mean duration of exposure to biologics was 28 months. A TNF
      antagonist was most frequently used as first-line biologic therapy (7/9), leading
      to partial or complete efficacy in six cases (85.7%). Loss of efficacy occurred
      in 5 cases. Abatacept (n=3) and tocilizumab (n=2) were effective as second-line
      biologic therapy while anakinra (n=2) and certolizumab (n=1) were not. Seven
      serious adverse drug reactions occurred, including 5 infections. CONCLUSIONS: TNF
      alpha antagonists may be proposed earlier in relapsing polychondritis to spare
      corticosteroids. Switching to another biologic can be proposed in case of loss of
      efficacy. Tocilizumab or abatacept can be proposed as third-line therapy. The
      benefit-to-risk ratio of biologics in relapsing polychondritis should be
      evaluated prospectively.

PMID- 24021707
TI  - Ambient air pollution and preeclampsia: a spatiotemporal analysis.
AB  - BACKGROUND: Available evidence concerning the association between air pollution
      and preeclampsia is limited, and specific associations with early- and late-onset
      preeclampsia have not been assessed. OBJECTIVES: We investigated the association,
      if any, between preeclampsia (all, early-, and late-onset) and exposure to
      nitrogen dioxide, nitrogen oxides, particulate matter with aerodynamic diameter
      <= 2.5 MUm (PM2.5; fine particles), <= 10 MUm, and 2.5-10 MUm, and PM2.5 light
      absorption (a proxy for elemental carbon) during the entire pregnancy and during
      the first, second, and third trimesters. METHODS: This study was based on 8,398
      pregnancies (including 103 cases of preeclampsia) among women residing in
      Barcelona, Spain (2000-2005). We applied a spatiotemporal exposure assessment
      framework using land use regression models to predict ambient pollutant levels
      during each week of pregnancy at the geocoded residence address of each woman at
      the time of birth. Logistic and conditional logistic regression models were used
      to estimate unadjusted and adjusted associations. RESULTS: We found positive
      associations for most of our evaluated outcome-exposure pairs, with the strongest
      associations observed for preeclampsia and late-onset preeclampsia in relation to
      the third-trimester exposure to fine particulate pollutants, and for early-onset
      preeclampsia in relation to the first-trimester exposure to fine particulate
      pollutants. Among our investigated associations, those of first- and third
      trimester exposures to PM2.5 and third-trimester exposure to PM2.5 absorbance and
      all preeclampsia, and third-trimester PM2.5 exposure and late-onset preeclampsia
      attained statistical significance. CONCLUSION: We observed increased risk of
      preeclampsia associated with exposure to fine particulate air pollution. Our
      findings, in combination with previous evidence suggesting distinct pathogenic
      mechanisms for early- and late-onset preeclampsia, support additional research on
      this topic.

PMID- 24021709
TI  - Comparative effects of carbohydrate versus fat restriction on serum levels of
      adipocytokines, markers of inflammation, and endothelial function among women
      with the metabolic syndrome: a randomized cross-over clinical trial.
AB  - BACKGROUND AND AIMS: Despite the efficacy of low-carbohydrate diets in the
      management of metabolic syndrome (MetS), it remains unknown if these favorable
      effects are mediated through changes in inflammation and endothelial dysfunction.
      We aimed to assess the effects of moderate substitution of dietary fats for
      carbohydrates on serum levels of adipocytokines, inflammatory indices, and
      biomarkers of endothelial function among women with the MetS. METHODS: In a
      randomized cross-over clinical trial, 30 overweight or obese (BMI >25) women with
      the MetS were randomly allocated to follow either a high-carbohydrate (HC) (60
      65% carbohydrates, 20-25% fats) diet or a moderately restricted carbohydrate
      (MRC) (43-47% carbohydrate, 36-40% fats) diet, each for 6 weeks. After a 2-week
      washout period, individuals were switched to the alternate diet for an additional
      6 weeks. In a fasted state, markers of inflammation [high-sensitivity C-reactive
      protein (hs-CRP), high-sensitivity interleukin-6 (hs-IL-6), high-sensitivity
      tumor necrosis factor-alpha (hs-TNF-alpha), and serum amyloid A (SAA)],
      endothelial function [E-selectin, serum intercellular adhesion molecule 1 (sICAM
      1), and serum vascular cell adhesion molecule 1 (sVCAM-1)], and adipocytokines
      (leptin and adiponectin) were measured in both study arms at baseline and after 6
      weeks. RESULTS: Consumption of an HC diet was associated with increased levels of
      SAA (3.27 +/- 1.22 MUg/ml) and decreased levels of adiponectin (-1.68 +/- 2.30
      ng/ml), while consumption of an MRC diet did not result in such unfavorable
      effects. Serum concentrations of leptin were reduced by the HC diet (p = 0.02),
      while they were not affected by the MRC diet. Changes in serum leptin levels were
      not significant between the two diets (p = 0.09). Serum concentrations of hs-CRP,
      hs-TNF-alpha, and IL-6 were not influenced by either diet. No significant
      differences between the two diets were found in terms of their effect on sICAM-1
      and sVCAM-1 concentrations. Adherence to both diets resulted in a 9 ng/ml
      decrease in serum E-selectin levels (p < 0.05 for both). CONCLUSIONS: Partial
      replacement of dietary carbohydrates by unsaturated fats prevents the increased
      levels of markers of systemic inflammation among women with the MetS.

PMID- 24021710
TI  - Microstructure of veneered zirconia after surface treatments: a TEM study.
AB  - OBJECTIVE: Clinical studies reveal that veneer chipping is one major problem
      associated with zirconia based dental restorations, the underlying mechanisms
      being still investigated. We semi-quantitatively analyzed the effects of
      different surface treatments (thermal etching, 35/105 MUm sandblasting and coarse
      bur drilling (150 MUm)) on the microstructure of a zirconia veneered dental
      ceramic. METHODS: The relative monoclinic content on zirconia surfaces was
      determined using X-ray diffraction (XRD). The microstructure at the zirconia
      veneer interface has thereafter been investigated using transmission electron
      microscopy (TEM). Selected area electron diffraction (SAED) was used to
      qualitatively assess the depth of the stress-induced phase transformation.
      RESULTS: Sandblasting or bur drilling significantly roughened the zirconia
      surface. A reverse transformation of already transformed monoclinic zirconia
      grains back into the tetragonal polymorph has been observed after thermal
      veneering treatment. In TEM, the mechanically treated samples revealed a highly
      damaged area of 1-3 MUm from the interface. The presence of monoclinic phase in
      veneered zirconia samples has been observed in SAED up to depths of 4 MUm (35 MUm
      sandblasted), 11 MUm (105 MUm sandblasted) and 9 MUm (150 MUm diamond drilled)
      below the interface. SIGNIFICANCE: Regardless of the treatment protocol and
      produced roughness, the veneering ceramic perfectly sealed the zirconia surface.
      XRD showed an increased amount of monoclinic phase on the surface treated
      zirconia. However after thermal treatment, the monoclinic phase was re
      transformed into the tetragonal polymorph. TEM/SAED analysis has found indication
      for a greater extend of the monoclinic transformation into the bulk zirconia
      compared to the treatment related defective zone depth.

PMID- 24021711
TI  - Dynamic cooperation and competition between brain systems during cognitive
      control.
AB  - The human brain is characterized by a remarkable ability to adapt its information
      processing based on current goals. This ability, which is encompassed by the
      psychological construct of cognitive control, involves activity throughout large
      scale, specialized brain systems that support segregated functions at rest and
      during active task performance. Based on recent research, we propose an account
      in which control functions rely on transitory changes in patterns of cooperation
      and competition between neural systems. This account challenges current
      conceptualizations of control as relying on segregated or antagonistic activity
      of specialized brain systems. Accordingly, we argue that the study of transitory
      task-based interactions between brain systems is critical to understanding the
      flexibility of normal cognitive control and its disruption in pathological
      conditions. 

PMID- 24021712
TI  - Hepatitis B virus in the State of Alagoas, Brazil: genotypes characterization and
      mutations of the precore and basal core promoter regions.
AB  - The aims of this study were to investigate the genotypes of hepatitis B virus and
      to identify the precore G1896A and basal core promoter A1762T/G1764A mutations in
      HBsAg and anti-HBc-positive patients. Eighty-three asymptomatic individuals,
      three with acute hepatitis B and 33 with chronic hepatitis B referred to viral
      hepatitis centers in the State of Alagoas, Brazil were analyzed according to
      their viral load, HBeAg/anti-HBe profile and alanine aminotransferase serum
      level. The genotypes identified were: A (92.5%), C (5%), D (1.25%) and F (1.25%).
      The precore mutation was detected in 3.8% of sequences and basal core promoter
      mutation in 52.4%. These were identified in 45.45% of the asymptomatic
      individuals and 54.55% of the patients with chronic hepatitis, irrespective of
      viral load and alanine aminotransferase serum level. In genotype C, only the
      basal core promoter mutation was identified and no mutations were identified in
      genotypes D and F. 

PMID- 24021713
TI  - Type D personality is associated with a sensitized cardiovascular response to
      recurrent stress in men.
AB  - The present study sought to examine the role of gender and Type D personality on
      cardiovascular reactivity to stress, by examining patterns of cardiovascular
      adaptation to recurrent laboratory-based stress. Cardiovascular data were
      collected from 76 students who, following an initial 10-min baseline period,
      underwent two cognitive stress tasks. Type D personality was assessed using the
      16-item Type D scale. Adaptation of cardiovascular response to recurrent stress
      was examined by scrutinizing the changes in systolic blood pressure (SBP),
      diastolic blood pressure (DBP), and heart rate (HR) across the procedure. Female
      participants and non-Type D males showed cardiovascular habituation to recurrent
      stress. For Type D males, however, cardiovascular sensitization was evident. The
      results implicate Type D personality in maladaptive cardiovascular responses,
      particularly in men, highlighting a possible direct mechanism of psychosomatic
      cardiovascular pathogenesis. 

PMID- 24021714
TI  - An unusual cuticular tumor-like growth on the abdomen of a lobster, Homarus
      americanus.
AB  - Tumors are rare in crustaceans, and whereas a few have been reported from the
      lobster Homarus americanus none have been adequately described. A lobster with an
      unusual, large, blue-colored tumor-like growth projecting laterally outward from
      the first abdominal somite was caught off Stonington, Maine, USA. The growth was
      rugose and covered by a relatively normal appearing cuticle with dispersed focal
      melanization. The underlying stroma consisted of an internal area of rescaffolded
      fibrous connective tissue, restructured muscle fibers, few arterioles, and an
      epidermal area comprised of columnar, highly vacuolated epithelial cells. No
      infectious pathogens or unusual inclusions were observed with microscopy and no
      eukaryotic pathogens were detected via molecular sequencing. Given the nature of
      the histology and the appearance of the growth, we identify the mass as a benign
      papilliform hamartoma that likely originated as a result of abnormal wound repair
      possibly initiated around ecdysis. This represents the first tumor-like hamartoma
      reported from a lobster, and the second hamartoma reported from a crustacean. 

PMID- 24021715
TI  - Proteolytic processing of Bacillus thuringiensis toxin Cry1Ab in rice brown
      planthopper, Nilaparvata lugens (Stal).
AB  - To understand the low toxicity of Cry toxins in planthoppers, proteolytic
      activation of Cry1Ab in Nilaparvata lugens was studied. The proteolytic
      processing of Cry1Ab protoxin by N. lugens midgut proteases was similar to that
      by trypsin activated Cry1Ab. The Cry1Ab processed with N. lugens midgut proteases
      was highly insecticidal against Plutella xylostella. However, Cry1Ab activated
      either by trypsin or the gut proteases of the brown planthopper showed low
      toxicity in N. lugens. Binding analysis showed that activated Cry1Ab bound to
      brush border membrane vesicles (BBMV) from N. lugens at a significantly lower
      level than to BBMV from P. xylostella. 

PMID- 24021716
TI  - Harmonic impedance spectra identification from time-varying bioimpedance: theory
      and validation.
AB  - The harmonic impedance spectra (HIS) of a time-varying bioimpedance Z(omega, t)
      is a new tool to better understand and describe complex time-varying biological
      systems with a distinctive periodic character as, for example, cardiovascular and
      respiratory systems. In this paper, the relationship between the experimental
      setup and the identification framework for estimating Z(omega, t) is set up. The
      theory developed applies to frequency response based impedance measurements from
      noisy current-voltage observations. We prove theoretically and experimentally
      that a voltage source (VS) and a current source (CS) analogue front end-based
      measurement lead, respectively, to a closed-loop and an open-loop HIS
      identification problem. Next, we delve into the estimation of the HIS by treating
      Z(omega, t), on the one hand, as a linear time-invariant (LTI) system within a
      short time window; and, on the other hand, as a linear periodically time-varying
      (PTV) system within the entire measurement interval. The LTI approach is based on
      the short-time Fourier transform (STFT), while the PTV approach relies on the
      information that is present in the skirts of the voltage and/or current spectra.
      In addition, direct and indirect methods are developed for estimating the HIS by
      using simple as well as more sophisticated techniques. Ultimately, the HIS and
      their uncertainty bounds are estimated from real measurements conducted on a
      periodically varying dummy impedance. 

PMID- 24021717
TI  - Studying the composition of mRNPs in vitro using splicing-competent cell
      extracts.
AB  - The correct processing and faithful decoding of mRNAs during gene expression
      depends on the interaction with RNA-binding proteins (RBPs). The association of
      RBPs with pre-mRNAs starts during transcription by RNA polymerase II and
      undergoes constant remodeling during pre-mRNA processing and later steps of genes
      expression. Recently developed high throughput methods enabled to define RBP
      binding sites in vivo and to identify a large number of novel RBPs in eukaryotic
      cells. However, the detailed characterization of RBP-RNA interactions as well as
      the analysis of functional RNPs is greatly facilitated by well-defined in vitro
      systems. Here, we describe a versatile method to study the assembly and splicing
      dependent remodeling of mRNPs in vitro. This method employs splicing-competent
      whole cell extracts (WCE) generated from transfected human embryonic kidney (HEK)
      293 cells. FLAG-tagged proteins present in the WCE are incorporated into mRNPs in
      vitro and afterwards used to immunoprecipitate substrate RNAs. We outline the
      principles of purifying in vitro assembled mRNPs and provide detailed protocols
      for the preparation and use of whole cell extracts. Alternative purification
      strategies and RNA substrates are discussed. 

PMID- 24021718
TI  - Production of pure and functional RNA for in vitro reconstitution experiments.
AB  - Reconstitution of protein complexes has been a valuable tool to test molecular
      functions and to interpret in vivo observations. In recent years, a large number
      of RNA-protein complexes has been identified to regulate gene expression and to
      be important for a range of cellular functions. In contrast to protein complexes,
      in vitro analyses of RNA-protein complexes are hampered by the fact that
      recombinant expression and purification of RNA molecules is more difficult and
      less well established than for proteins. Here we review the current state of
      technology available for in vitro experiments with RNAs. We outline the
      possibilities to produce and purify large amounts of homogenous RNA and to
      perform the required quality controls. RNA-specific problems such as degradation,
      5' and 3' end heterogeneity, co-existence of different folding states, and
      prerequisites for reconstituting RNAs with recombinantly expressed proteins are
      discussed. Additionally a number of techniques for the characterization of direct
      and indirect RNA-protein interactions are explained. 

PMID- 24021719
TI  - Alternative flame retardants, Dechlorane Plus and BDEs in the blubber of harbour
      porpoises (Phocoena phocoena) stranded or bycaught in the UK during 2008.
AB  - Thirty alternative flame retardant compounds and a suite of 17 brominated
      diphenyl ether (BDE) congeners were determined in the blubber of 21 harbour
      porpoises stranded or bycaught around UK coasts during 2008 using GC-MS/MS. Of
      the 30 compounds, 19 were not detected. Of the remaining 11 compounds, some fell
      below the lowest calibration level and so were recorded as less than values, but
      were certainly present in the blubber samples (examples include tetrabromo-p
      xylene (TBX), tetrabromo-o-chlorotoluene (TBCT) and 2,3-dibromopropyl-2,4,6
      tribromophenyl ether (TBP-DBPE). Concentrations were low, the highest
      concentration being only 35MUgkg(-1) wet weight. This contrasted with those of
      the BDEs, summed concentrations which ranged from 54.6 to 913MUgkg(-1) wet
      weight, although levels in porpoise blubber have been declining since 1998. Both
      Dechlorane Plus (DDC-CO) isomers were detected in some samples, suggesting either
      that this product has been used in the UK or that its presence may result from
      atmospheric transport from source regions. BDE183, a marker for the octa-mix PBDE
      product, was found at low concentrations (0.63 to 1.7MUgkg(-1) wet weight) and
      the four nona- and deca-BDE congeners were not detected in any sample. 

PMID- 24021720
TI  - Investigation of polycyclic aromatic hydrocarbon level in blood and semen quality
      for residents in Pearl River Delta Region in China.
AB  - This study is the first one investigating the correlation between the
      concentration of polycyclic aromatic hydrocarbon (PAHs) in blood and semen
      qualities for residents in the Pearl River Delta (PRD) region in China. Blood
      samples from 53 infertile volunteers were studied for measures of semen quality
      and 16 PAHs. Information on the study subjects' living habits (such as smoking,
      drinking and preference of consumption for food) and general information (age,
      body-mass-index (BMI) and educational background) were also collected.
      Statistical results showed that age and BMI were significantly and negatively
      related to semen motilities. The total concentrations of PAHs (?16 PAHs) in the
      blood were 12,010, 7493, 9105 and 8647ng/g for factory workers, office workers,
      technicians and salespersons, respectively. In addition, ?16 PAHs in the blood of
      smokers, drinkers and heavy-taste food consumers were 11,950, 11,266 and
      12,141ng/g, which were higher than those observed in nonsmokers (10,457ng/g),
      nondrinkers (10,920ng/g) and light-taste food consumers (9202ng/g), individually.
      Furthermore, the Pearson correlation analysis results showed significant positive
      correlations between BMI and ?16 PAHs in the blood. Statistically significant
      correlations were observed between semen motilities and ?16 PAHs in the blood as
      well. Logistic regression results showed that for each 1ng/g increase in ?16 PAHs
      in blood samples, the log odds of experiencing a pregnancy decrease by 0.039 on
      average. However, more evidences are needed to clarify the impact of PAHs in the
      blood to male infertility. 

PMID- 24021721
TI  - A comparative study of solid carbon acid catalysts for the esterification of free
      fatty acids for biodiesel production. Evidence for the leaching of colloidal
      carbon.
AB  - The preparation of a variety of sulfonated carbons and their use in the
      esterification of oleic acid is reported. All sulfonated materials show some loss
      in activity associated with the leaching of active sites. Exhaustive leaching
      shows that a finite amount of activity is lost from the carbons in the form of
      colloids. Fully leached catalysts show no loss in activity upon recycling. The
      best catalysts; 1, 3, and 6; show initial TOFs of 0.07 s(-1), 0.05 s(-1), and
      0.14 s(-1), respectively. These compare favorably with literature values.
      Significantly, the leachate solutions obtained from catalysts 1, 3, and 6, also
      show excellent esterification activity. The results of TEM and catalyst poisoning
      experiments on the leachate solutions associate the catalytic activity of these
      solutions with carbon colloids. This mechanism for leaching active sites from
      sulfonated carbons is previously unrecognized.

PMID- 24021722
TI  - Poor description of non-pharmacological interventions: analysis of consecutive
      sample of randomised trials.
AB  - OBJECTIVES: To evaluate the completeness of descriptions of non-pharmacological
      interventions in randomised trials, identify which elements are most frequently
      missing, and assess whether authors can provide missing details. DESIGN: Analysis
      of consecutive sample of randomised trials of non-pharmacological interventions.
      DATA SOURCES AND STUDY SELECTION: All reports of randomised trials of non
      pharmacological interventions published in 2009 in six leading general medical
      journals; 133 trial reports, with 137 interventions, met the inclusion criteria.
      DATA COLLECTION: Using an eight item checklist, two raters assessed the primary
      full trial report, plus any reference materials, appendices, or websites.
      Questions about missing details were emailed to corresponding authors, and
      relevant items were then reassessed. RESULTS: Of 137 interventions, only 53 (39%)
      were adequately described; this was increased to 81 (59%) by using 63 responses
      from 88 contacted authors. The most frequently missing item was the "intervention
      materials" (47% complete), but it also improved the most after author response
      (92% complete). Whereas some authors (27/70) provided materials or further
      information, other authors (21/70) could not; their reasons included copyright or
      intellectual property concerns, not having the materials or intervention details,
      or being unaware of their importance. Although 46 (34%) trial interventions had
      further information or materials readily available on a website, many were not
      mentioned in the report, were not freely accessible, or the URL was no longer
      functioning. CONCLUSIONS: Missing essential information about interventions is a
      frequent, yet remediable, contributor to the worldwide waste in research funding.
      If trial reports do not have a sufficient description of interventions, other
      researchers cannot build on the findings, and clinicians and patients cannot
      reliably implement useful interventions. Improvement will require action by
      funders, researchers, and publishers, aided by long term repositories of
      materials linked to publications.

PMID- 24021723
TI  - Participants' experiences of facilitated physical activity for the management of
      depression in primary care.
AB  - A qualitative study was conducted within a randomised trial of facilitated
      physical activity for depression based on Self-Determination Theory and
      motivational interviewing. Interviews were held with 19 participants at 4 months,
      and 12 participants were re-interviewed 8 months later. The interviews were
      analysed in accordance with Grounded Theory using framework. Themes consisted of
      the following: relationship with the physical activity facilitators, mode of
      facilitation, impact of contact with physical activity facilitator/assimilation
      and future plans, change in activity, and effectiveness of physical activity
      facilitator techniques. Engagement in physical activity was enhanced within an
      autonomy-supportive environment. 

PMID- 24021724
TI  - Target capture and massively parallel sequencing of ultraconserved elements for
      comparative studies at shallow evolutionary time scales.
AB  - Comparative genetic studies of non-model organisms are transforming rapidly due
      to major advances in sequencing technology. A limiting factor in these studies
      has been the identification and screening of orthologous loci across an
      evolutionarily distant set of taxa. Here, we evaluate the efficacy of genomic
      markers targeting ultraconserved DNA elements (UCEs) for analyses at shallow
      evolutionary timescales. Using sequence capture and massively parallel sequencing
      to generate UCE data for five co-distributed Neotropical rainforest bird species,
      we recovered 776-1516 UCE loci across the five species. Across species, 53-77% of
      the loci were polymorphic, containing between 2.0 and 3.2 variable sites per
      polymorphic locus, on average. We performed species tree construction, coalescent
      modeling, and species delimitation, and we found that the five co-distributed
      species exhibited discordant phylogeographic histories. We also found that
      species trees and divergence times estimated from UCEs were similar to the
      parameters obtained from mtDNA. The species that inhabit the understory had older
      divergence times across barriers, contained a higher number of cryptic species,
      and exhibited larger effective population sizes relative to the species
      inhabiting the canopy. Because orthologous UCEs can be obtained from a wide array
      of taxa, are polymorphic at shallow evolutionary timescales, and can be generated
      rapidly at low cost, they are an effective genetic marker for studies
      investigating evolutionary patterns and processes at shallow timescales.

PMID- 24021725
TI  - Formosa arctica sp. nov., isolated from Arctic seawater.
AB  - A Gram-staining-negative, chemoheterotrophic, yellow-pigmented, gliding, catalase
      and oxidase-positive, flexirubin-negative, strictly aerobic bacterium,
      designated strain IMCC9485(T), was isolated from a seawater sample collected from
      the Arctic Ocean. Optimal growth of strain IMCC9485(T) was observed at 25 
      degrees C, pH 7-8 and in the presence of 1.5-2.5 % NaCl. Phylogenetic analysis
      based on 16S rRNA gene sequences showed that strain IMCC9485(T) belonged to the
      genus Formosa and was closely related to Formosa algae KCTC 12364(T) (98.2 %) and
      Formosa agariphila KCTC 12365(T) (98.0 %). DNA-DNA relatedness between the new
      isolate and F. algae and F. agariphila was far lower than 70 %, which indicated
      that strain IMCC9485(T) is a novel genomic species of the genus Formosa. The
      major fatty acids (>10 %) were iso-C15 : 1G (13.7 %), C16 : 1omega7c and/or C16 :
      1omega6c (13.4 %) and iso-C15 : 0 (12.3 %). The G+C content of the genomic DNA
      was 37.6 mol%. Strain IMCC9485(T) contained menaquinone-6 (MK-6) as the
      respiratory quinone and phosphatidylethanolamine, unknown aminophospholipids and
      unknown polar lipids as polar lipid constituents. On the basis of phylogenetic
      analyses and differential phenotypic characteristics, it is suggested that strain
      IMCC9485(T) ( = KACC 17484(T) = KCCM 42937(T) = NBRC 106080(T)) be assigned to
      the genus Formosa as the type strain of a novel species, for which the name
      Formosa arctica sp. nov. is proposed. 

PMID- 24021726
TI  - Pseudomonas chengduensis sp. nov., isolated from landfill leachate.
AB  - Strain MBR(T) was isolated from landfill leachate in a solid-waste disposal site
      in Chengdu, Sichuan, China. An analysis of 16S rRNA gene sequences revealed that
      the isolate was closely related to members of the genus Pseudomonas, sharing the
      highest sequence similarities with Pseudomonas toyotomiensis HT-3(T) (99.8 %),
      Pseudomonas alcaliphila AL15-21(T) (99.7 %) and Pseudomonas oleovorans ATCC
      8062(T) (99.4 %). Multi-locus sequence analysis based on three housekeeping genes
      (gyrB, rpoB and rpoD) provided higher resolution at the species level than that
      based on 16S rRNA gene sequences, which was further confirmed by less than 70 %
      DNA-DNA relatedness between the new isolate and P. toyotomiensis HT-3(T) (61.3
      %), P. alcaliphila AL15-21(T) (51.5 %) and P. oleovorans ATCC 8062(T) (57.8 %).
      The DNA G+C content of strain MBR(T) was 61.9 mol% and the major ubiquinone was Q
      9. The major cellular fatty acids (>10 %) were C18 : 1omega7c and/or C18 :
      1omega6c, C16 : 0, and C16 : 1omega7c and/or C16 : 1omega6c. Polyphasic analysis
      indicates that strain MBR(T) represents a novel species of the genus Pseudomonas,
      for which the name Pseudomonas chengduensis sp. nov. is proposed. The type strain
      is MBR(T) ( = CGMCC 2318(T) = DSM 26382(T)). 

PMID- 24021727
TI  - Thalassospira alkalitolerans sp. nov. and Thalassospira mesophila sp. nov.,
      isolated from a decaying bamboo sunken in the marine environment, and emended
      description of the genus Thalassospira.
AB  - Two marine bacteria, designated strains MBE#61(T) and MBE#74(T), were isolated
      from a piece of sunken bamboo in the marine environment in Japan. Both of these
      strains were Gram-stain-negative, but had different cell shapes: MBE#61(T) was
      spiral, whereas MBE#74(T) was rod-shaped. The temperature, pH and salt
      concentration ranges for growth of strain MBE#61(T) were 4-38  degrees C (optimal
      at 32  degrees C), pH 4.5-11.0 (optimal at pH 7.0-8.0) and 1-11 % (optimal at 2
      %) NaCl, whereas those of strain MBE#74(T) were 4-36  degrees C (optimal at 30 
      degrees C), pH 4.0-10.5 (optimal at pH 7.0-8.0) and 1-12 % (optimal at 4 %) NaCl.
      Phylogenetic analysis based on partial 16S rRNA gene sequences revealed that both
      strains belong to the genus Thalassospira within the class Alphaproteobacteria.
      Similarity between the 16S rRNA gene sequence of strain MBE#61(T) and those of
      the type strains of species of the genus Thalassospira was 97.5-99.0 %, and that
      of strain MBE#74(T) was 96.9-98.6 %; these two isolates were most closely related
      to Thalassospira lucentensis QMT2(T). However, the DNA-DNA hybridization values
      between T. lucentensis QMT2(T) and strain MBE#61(T) or MBE#74(T) were only 16.0 %
      and 7.1 %, respectively. The DNA G+C content of strain MBE#61(T) was 54.4 mol%,
      and that of strain MBE#74(T) was 55.9 mol%. The predominant isoprenoid quinone of
      the two strains was Q-10 (MBE#61(T), 97.3 %; MBE#74(T), 93.5 %). The major
      cellular fatty acids of strain MBE#61(T) were C18 : 1omega7c (31.1 %), summed
      feature 3 comprising C16 : 0omega7c/iso-C15 : 0 2-OH (26.1 %) and C16 : 0 (20.9
      %); those of strain MBE#74(T) were C16 : 0 (26.2 %), C17 : 0 cyclo (19.9 %) and
      C18 : 1omega7c (12.1 %). On the basis of these results, strain MBE#61(T) and
      strain MBE#74(T) are considered to represent novel species of the genus
      Thalassospira, for which names Thalassospira alkalitolerans sp. nov. and
      Thalassospira mesophila sp. nov. are proposed. The type strains are MBE#61(T) ( =
      JCM 18968(T) = CECT 8273(T)) and MBE#74(T) ( = JCM 18969(T) = CECT 8274(T)),
      respectively. An emended description of the genus Thalassospira is also proposed.

PMID- 24021728
TI  - Pseudoalteromonas shioyasakiensis sp. nov., a marine polysaccharide-producing
      bacterium.
AB  - A novel exopolysaccharide-producing bacterium, designated strain SE3(T), was
      isolated from Pacific Ocean sediment. The strain was Gram-stain-negative, motile,
      strictly aerobic, oxidase-positive and catalase-positive, and required Na(+) for
      growth. Its major isoprenoid quinone was ubiquinone-8 (Q-8), and its cellular
      fatty acid profile mainly consisted of C16 : 1omega7c, C16 : 0 and C18 :
      1omega7c. The DNA G+C content was 46.9 mol%. 16S rRNA gene sequence analysis
      suggested that strain SE3(T) is a member of the genus Pseudoalteromonas. Strain
      SE3(T) exhibited close phylogenetic affinity to Pseudoalteromonas arabiensis JCM
      17292(T) (99.0 % 16S rRNA gene sequence similarity), Pseudoalteromonas lipolytica
      LMEB 39(T) (98.39 %) and Pseudoalteromonas donghaensis HJ51(T) (97.65 %). The DNA
      DNA reassociation values between strain SE3(T) and P. arabiensis JCM 17292(T), P.
      lipolytica JCM 15903(T) and P. donghaensis LMG 24469(T) were 31, 26 and 44 %,
      respectively. Owing to the significant differences in phenotypic and
      chemotaxonomic characteristics, phylogenetic analysis based on 16S rRNA gene
      sequences and DNA-DNA relatedness data, the new isolate merits classification as
      a representative of novel species, for which the name Pseudoalteromonas
      shioyasakiensis is proposed. The type strain is SE3(T) ( = JCM 18891(T) = NCIMB
      14852(T)). 

PMID- 24021729
TI  - Cohnella lupini sp. nov., an endophytic bacterium isolated from root nodules of
      Lupinus albus.
AB  - A bacterial strain designated RLAHU4B(T) was isolated from root nodules of
      Lupinus albus in Leon (Spain). The 16S rRNA gene sequence of this strain showed
      similarities lower than 97 % with respect to species of the genus Cohnella. The
      strain was a Gram-variable, sporulating rod, motile by means of peritrichous
      flagella, and facultatively anaerobic. It was positive for oxidase, catalase and
      beta-galactosidase production but negative for urease, amylase and gelatinase.
      Strain RLAHU4B(T) grew in the presence of 5 % NaCl. MK-7 was the predominant
      menaquinone and meso-diaminopimelic acid was present in the peptidoglycan.
      anteiso-C15 : 0, iso-C16 : 0, iso-C15 : 0 and C16 : 0 were the major fatty acids.
      Major polar lipids of strain RLAHU4B(T) were diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylethanolamine, three unknown phospholipids, two
      unknown aminophospholipids and one unknown lipid. The DNA G+C content was 57.8
      mol%. Strain RLAHU4B(T) presented phenotypic differences from all recognized
      species of the genus Cohnella. The phylogenetic, chemotaxonomic and phenotypic
      data indicated that strain RLAHU4B(T) belongs to a novel species of the genus
      Cohnella, for which the name Cohnella lupini sp. nov. is proposed, with strain
      RLAHU4B(T) ( = LMG 27416(T) = CECT 8236(T)) as the type strain. 

PMID- 24021730
TI  - Bacillus pervagus sp. nov. and Bacillus andreesenii sp. nov., isolated from a
      composting reactor.
AB  - Two strains, 8-4-E12(T) and 8-4-E13(T), were isolated from a biowaste composting
      reactor. Based on 16S rRNA gene sequences, both strains belong to the genus
      Bacillus. Strain 8-4-E12(T) was most closely related to the type strains of
      Bacillus shackletonii, B. acidicola, B. sporothermodurans and B. oleronius (96.4,
      96.3, 96.0 and 95.6 % 16S rRNA gene similarity, respectively), whereas strain 8-4
      E13(T) was most closely related to the type strain of Bacillus humi (96.5 %
      sequence similarity). Strains 8-4-E12(T) and 8-4-E13(T) shared 94 % 16S rRNA gene
      sequence similarity. The fatty acid profile of strain 8-4-E12(T) was dominated by
      saturated iso- and anteiso-branched fatty acids (iso-C15 : 0, anteiso-C15 : 0,
      anteiso-C17 : 0 and iso-C16 : 0), and also contained considerable amounts of C16
      : 0. The fatty acid profile of strain 8-4-E13(T) showed a predominance of iso-C15
      : 0 (65 %), with smaller amounts of other saturated branched-chain fatty acids
      along with an unsaturated alcohol. Both strains contained diphosphatidylglycerol,
      phosphatidylglycerol and phosphatidylethanolamine as major polar lipids.
      Additionally, strain 8-4-E12(T) contained an unknown lipid and strain 8-4-E13(T)
      two unknown (amino-)phospholipids. The diagnostic diamino acid found in the cell
      wall peptidoglycan of 8-4-E12(T) and 8-4-E13(T) was meso-diaminopimelic acid. The
      predominant menaquinone was MK-7. The results of physiological and biochemical
      tests also allowed phenotypic differentiation of the two strains from each other
      and from related Bacillus species. On the basis of their phylogenetic, phenotypic
      and chemotaxonomic properties, strains 8-4-E12(T) and 8-4-E13(T) represent novel
      species of the genus Bacillus, for which the names Bacillus pervagus sp. nov.
      (type strain 8-4-E12(T) = DSM 23947(T) = LMG 27601(T)) and Bacillus andreesenii
      sp. nov. (type strain 8-4-E13(T) = DSM 23948(T) = LMG 27602(T)) are proposed. 

PMID- 24021731
TI  - Zoledronic acid impairs re-epithelialization through down-regulation of integrin
      alphavbeta6 and transforming growth factor beta signalling in a three-dimensional
      in vitro wound healing model.
AB  - This study examined the negative effects of zoledronic acid on the re
      epithelialization of oral mucosa in a three-dimensional in vitro oral mucosa
      wound healing model. A living oral mucosa equivalent was constructed by seeding a
      mixture of primary human oral keratinocytes and fibroblasts, at a cell density of
      1.5 * 10(5)cm(2) each, onto human cadaver dermis. This was cultured in a
      submerged condition in 1.2mM Ca(2+) EpiLife for 5 days, and then in an air-liquid
      interface for 14 days. The equivalent was wounded by excising a linear 2-mm-wide
      epithelial layer on day 8 and subsequently incubated with 10 MUM zoledronic acid
      for an additional 11 days. Histological and immunohistochemical observations
      revealed zoledronic acid to significantly suppress the epithelial thickness and
      Ki-67-labelling index. Zoledronic acid also abolished integrin alphavbeta6
      expression, implying impaired keratinocyte migration. Zoledronic acid did not
      attenuate the total transforming growth factor beta 1 (TGF-beta1) production into
      the supernatant, but down-regulated TGF-beta receptor types I and II expression
      and Smad3 phosphorylation, as was also confirmed by immunofluorescence
      microscopy. This study therefore showed zoledronic acid to abrogate integrin
      alphavbeta6 expression, cause the down-regulation of TGF-beta/Smad signalling in
      oral keratinocytes, and impair re-epithelialization, suggesting compromised oral
      mucosa homeostasis in patients receiving zoledronic acid.

PMID- 24021732
TI  - Clinical utility of endoscopic ultrasound-guided fine-needle aspiration in the
      diagnosis of mediastinal and intra-abdominal lymphadenopathy.
AB  - INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has
      proven to be helpful in obtaining tissue samples from enlarged mediastinal and
      intra-abdominal lymph nodes. This is especially beneficial in the diagnosis and
      staging of malignancy. We retrospectively reviewed the clinical utility of this
      method at a tertiary care cancer hospital in Pakistan. PATIENTS AND METHODS: The
      medical records of 183 consecutive patients referred to the gastroenterology
      service from August 2008 to March 2012 were reviewed in this retrospective study.
      The mean age of the patients at presentation was 46.7 years (range 6-87; 62%
      males); 119 patients had mediastinal and 64 had intra-abdominal lymphadenopathy.
      Major indications for referral were diagnosis of lymphadenopathy of unknown
      origin detected on CT scan or PET-CT, to exclude lymph node metastasis in
      patients with a known primary tumor and to rule out relapse of lymphoma following
      treatment or during follow-up. Rapid on-site evaluation (ROSE) was performed in
      all patients to confirm the adequacy of sampling, followed by definitive
      cytopathological evaluation. RESULTS: EUS-FNA with ROSE obtained adequate tissue
      for cytology in 97.3% of the patients in this cohort. These results were further
      confirmed on final cytopathological analysis in 96.2% of patients. Two patients
      (1.1%) had inadequate specimens for final interpretation (97.3 vs. 96.2; p =
      0.001). Clinical utility was 95% for mediastinal lymphadenopathy and 98.4% for
      intra-abdominal lymphadenopathy. Only 1 patient had a serious complication
      requiring hospitalization and this was successfully managed conservatively.
      CONCLUSION: EUS-FNA is safe and has a high clinical utility in diagnosing
      unexplained mediastinal and intra-abdominal lymphadenopathy.

PMID- 24021734
TI  - Day-to-day variation in food intake and energy expenditure in healthy women: the
      Dietitian II Study.
AB  - Because day-to-day food intake varies, we tested the hypothesis that ad libitum
      food intake and energy expenditure show corrective responses over periods of 1 to
      10 days in healthy young women. Food intake and accelerometry measurements were
      collected daily for 17 days in 15 young women. Total daily energy expenditure
      (TDEE) using doubly labeled water was also measured. The daily deviations in
      macronutrient and energy intake and energy expenditure from the average values
      were compared with the deviations observed over succeeding intervals to estimate
      the corrective responses. The intraindividual coefficients of variation for
      energy intake averaged +/-25%, ranging from 16% to 34%. TDEE had a coefficient of
      variation of 8.3%, and accelerometry had a coefficient of variation of 8.4%
      (range=4.6% to 16.4%). Energy expenditure by accelerometry (2,087+/-191 kcal/day)
      was not significantly different from TDEE (2,128+/-177 kcal/day), but reported
      daily energy intake was 20.4% lower (1,693+/-276 kcal/day). There were
      significant corrective responses in energy from fat and total energy intake. This
      occurred from Days 3 to 6, with a peak at Day 5 that disappeared when data were
      randomized within each subject. Human beings show corrective responses to
      deviations from average energy and macronutrient intakes with a lag time of 3 to
      6 days, but not 1 to 2 days. These corrective responses are likely to play a role
      in bringing about weight stability. 

PMID- 24021735
TI  - Group and individual agreement between field and dual X-ray absorptiometry-based
      body composition techniques in children from standard schools and a sports
      academy.
AB  - Percentage fat (%FM) and fat-free mass (FFM) were measured in 37 children from a
      sports academy and in 71 children from standard schools with dual x-ray
      absorptiometry (DXA) and bioelectrical impedance analysis (BIA) using the
      manufacturer's equation (Tanita) and an ethnic-specific prediction equation
      (Haroun). In the standard school, BIA overestimated FFM and underestimated %FM by
      a mean of 2.5 kg and 5.2%, respectively, using the Tanita equation. In girls from
      the sports academy, the Tanita equation underestimated FFM and overestimated %FM
      compared with DXA (mean difference BIA-DXA; FFM: -1.3 kg; %FM: 1.8%). The Haroun
      equation improved mean agreement between BIA and DXA in children (11 to 15 years)
      from the sports academy and for boys from standard schools, but reduced accuracy
      on individual assessments. These results have important practice implications for
      dietetics practitioners specializing in sports nutrition and exercise trainers. 

PMID- 24021733
TI  - A randomized controlled trial of a theoretically-based behavioral nutrition
      intervention for community elders: lessons learned from the Behavioral Nutrition
      Intervention for Community Elders Study.
AB  - Older adults with multiple comorbidities are often undernourished or at high risk
      for becoming so, especially after a recent hospitalization. Randomized controlled
      trials of effective, innovative interventions are needed to support evidence
      based approaches for solving nutritional problems in this population. Self
      management approaches where participants select their own behavioral goals can
      enhance success of interventions. The purpose of this study was to evaluate the
      feasibility and efficacy of a multilevel self-management intervention to improve
      nutritional status in a group of high-risk older adults. The Behavioral Nutrition
      Intervention for Community Elders (B-NICE) trial used a prospective randomized
      controlled design to determine whether the intervention, compared to standard
      care, maintained or increased caloric intake (depending on baseline body mass
      index) and, consequently, stabilized or increased body weight. Participants were
      34 Medicare-eligible, age 65 years old or older, homebound adults who were
      consuming insufficient calories and/or had a history of weight loss >=2.5% over 6
      months. The intervention took place within participants' homes. Outcome measures,
      including energy intake (based on collection of three 24-hour dietary recalls)
      and body weights were assessed at baseline and at 60 days post randomization. The
      primary analyses included analyses of covariance and Pearson's chi(2). We
      hypothesized that the intervention would result in increased caloric intake and
      weight gain in underweight older adults and increased or stabilized caloric
      intake and weight for everyone else. The intervention was feasible; however, it
      did not result in differences between groups for desired outcomes of either
      caloric intake or body weight. Future interventions might either deliberately
      involve caregivers or reduce burden for both patients and caregivers. 

PMID- 24021736
TI  - Type II and IIIA thumb hypoplasia reconstruction.
AB  - Thumb hypoplasia treatment requires considering every component of the
      maldevelopment. Types II and IIIA hypoplasia share common features such as first
      web space narrowing, hypoplasia or absence of thenar muscles and
      metacarpophalangeal joint instability. Many surgical techniques to correct the
      malformation have been described. We report our surgical strategy that includes
      modifications of the usual technique that we found useful in reducing morbidity
      while optimizing the results. A diamond-shape kite flap was used to widen the
      first web space. Its design allowed primary closure of the donor site using a
      Dufourmentel flap. The ring finger flexor digitorum superficialis was transferred
      for opposition transfer, and the same tendon was used to stabilize the
      metacarpophalangeal joint on its ulnar and/or radial side depending on a
      uniplanar or more global instability. An omega-shaped K-wire was placed between
      the first and second metacarpals to maintain a wide opening of the first web
      space without stressing the reconstructed ulnar collateral ligament of the MCP
      joint. We report a clinical series of 15 patients (18 thumbs) who had this
      reconstructive program. 

PMID- 24021738
TI  - Deep digital burns treated with 2 abdominal flaps: case report.
AB  - We present the case of a 22-year-old man with third- to fourth-degree flame burns
      to all fingers of the right hand. After removing the necrotic tissues and
      amputating the carbonized distal segments of each finger, we covered the injured
      thumb with a paraumbilical tubular flap and covered the other fingers with an
      abdominal wall marsupial flap. Fifty days after injury, all the wounds healed,
      and the remaining fingers were salvaged. Four months after injury, the grip
      strength and the first web span of the right hand was 23.6 kg and 53 degrees ,
      and the patient could fulfill almost all the activities of daily living. 

PMID- 24021737
TI  - Effect of pisiform excision or pisotriquetral arthrodesis as a treatment for
      pisotriquetral arthritis: a biomechanical study.
AB  - PURPOSE: To determine whether flexor carpi ulnaris (FCU) forces and tendon
      displacements change after pisotriquetral arthrodesis or after pisiform excision.
      METHODS: Nine cadaver wrists were moved through 4 variations of a dart throw
      motion, each having an oblique plane of motion, but with different ranges of
      motion and different antagonistic forces. The FCU tendon force and movement were
      measured in the intact wrist, following pisotriquetral arthrodesis, and following
      pisiform excision. Changes in force and tendon movement were compared using a
      repeated measures analysis of variance. RESULTS: After excision of the pisiform,
      a significantly greater FCU force was required during the 2 variations of the
      dart throw motion having a larger range of motion and during the smaller motion
      having a larger antagonistic force. Pisotriquetral arthrodesis did not cause a
      significant increase in the peak FCU force. Excision of the pisiform caused the
      FCU tendon to significantly retract during all wrist motions as compared to the
      intact wrist or after pisotriquetral arthrodesis. CONCLUSIONS: Greater FCU forces
      are required to move the wrist when the pisiform with its moment arm function has
      been removed. This occurs during large oblique plane wrist motions and also in a
      smaller motion when greater antagonistic forces are applied. Excision of the
      pisiform also allows the FCU to move proximally, again because its moment arm
      function has been eliminated. CLINICAL RELEVANCE: Excision of the pisiform
      requires greater FCU forces during large wrist motions and during motions that
      include large gripping forces such that excision may be a concern in high-demand
      patients with pisotriquetral arthritis. Although pisotriquetral arthrodesis does
      not alter the mechanical advantage of the FCU, its use in high-demand patients
      with pisotriquetral osteoarthritis cannot yet be recommended until the effects of
      that arthrodesis on midcarpal kinematics are further clarified.

PMID- 24021739
TI  - Dosage of local anesthesia in wide awake hand surgery.

PMID- 24021740
TI  - Distraction for proximal interphalangeal joint contractures: long-term results.
AB  - PURPOSE: To report the medium- to long-term outcomes of joint distraction using a
      unilateral external fixator in the treatment of chronic post-traumatic proximal
      interphalangaeal (PIP) joint contractures. METHOD: Between September 2001 and
      October 2011, 94 consecutive patients (98 PIP joints) with a mean age of 43 years
      (range, 17-69 y) were treated with external fixation for chronic flexion
      deformity of the PIP joint from trauma. The average time from injury to surgery
      was 48 months (range, 6-84 mo), and the duration of joint distraction was 10 days
      (range, 7-22 d). Patients were followed for a mean period of 54 months (range, 12
      72 mo). RESULTS: The average gain in joint flexion was 25 degrees  and in joint
      extension was 40 degrees . The mean improvement in the active range of movement
      was 67 degrees  (range. 30 degrees -90 degrees ). There was no loss of motion on
      the latest follow-up. Patients younger than 40 years fared slightly better than
      those older than 40 years. Two patients developed swelling, pain, and erythema
      during treatment, which resolved upon temporarily stopping the distraction
      process. There were 12 cases of superficial pin-site infections, which were
      managed conservatively without serious complications or adverse outcome.
      CONCLUSIONS: External fixation is a simple and effective treatment modality for
      chronic traumatic PIP joint contractures with good predictable medium- to long
      term results. Careful patient selection and monitoring are required.

PMID- 24021741
TI  - Acute idiopathic blue finger: case report.
AB  - An acute blue finger is an uncommon but potentially serious finding with a
      heterogeneous etiology. A rare group of patients will present with acute,
      atraumatic, nonischemic blue fingers. The clinical course of these patients
      appears to be benign. We describe the presentation of an otherwise healthy 22
      year-old woman with an acute idiopathic blue finger. We highlight the
      differential diagnoses and evaluation of this rare condition. 

PMID- 24021742
TI  - Treatment of split-thickness skin graft-related forearm scar contractures with a
      carbon dioxide laser protocol: 3 case reports.
AB  - Split-thickness skin grafts in the forearm can lead to motion restriction and
      disability through the dense scarring of the skin and formation of graft-tendon
      adhesions. Three patients were referred for laser treatment of motion-limiting
      scar-associated split-thickness skin grafts to the forearm. All patients had
      reached a plateau in range of motion despite aggressive hand therapy and
      underwent serial laser scar treatments at 6- to 8-week intervals. Treatments were
      performed in a clinic setting and were initiated 2 to 5 months after
      reconstructive surgery. Rapid subjective functional and objective improvements in
      range of motion were noted after laser therapy. Results were cumulative and
      durable at final follow-up ranging from 10 to 15 months after the initial
      treatment. No complications were noted. Fractionated carbon dioxide laser therapy
      is a promising adjunct to hand therapy when the main restraint to motion is
      superficial skin scarring and skin-tendon adhesions. 

PMID- 24021743
TI  - Hand and wrist injuries in golf.

PMID- 24021744
TI  - Regeneration of spermatogenesis after testicular cancer chemotherapy.
AB  - PURPOSE: Azoospermia is a common side effect of chemotherapy. Although most
      patients restore spermatogenesis over time, the exact time course has not been
      well described. We analyzed the recovery of spermatogenesis in testicular cancer
      patients following chemotherapy. PATIENTS AND METHODS: 49 patients, consisting of
      45 treated with a bleomycin, etoposide and cisplatin (BEP) regimen and 4 with
      high-dose chemotherapy, were followed up with occasional semen analyses. The
      primary endpoint of this study was the confirmation of motile spermatozoa in the
      patients' semen. RESULTS: Among 45 patients treated with BEP, 44 recovered
      spermatogenesis. The recovery of spermatogenesis was delayed depending on the
      increase in BEP cycles. In groups of patients who received 1-2, 3 and 4 cycles,
      the recovery rates of spermatogenesis within 2 year were 83.3, 80.0 and 66.7%,
      respectively. In the group with 5-6 cycles of BEP, re-spermatogenesis was
      significantly delayed and no patients re-established spermatogenesis within 2
      years. The patients' age and semen parameters before chemotherapy were not useful
      as predictive factors for the recovery of spermatogenesis. CONCLUSION: The
      recovery of spermatogenesis was rather fast and was often observed as early as
      several months after BEP treatment when the number of cycles was <4.

PMID- 24021745
TI  - Improved Cole parameter extraction based on the least absolute deviation method.
AB  - The Cole function is widely used in bioimpedance spectroscopy (BIS) applications.
      Fitting the measured BIS data onto the model and then extracting the Cole
      parameters (R0, Rinfinity, alpha and tau) is a common practice. Accurate
      extraction of the Cole parameters from the measured BIS data has great
      significance for evaluating the physiological or pathological status of
      biological tissue. The traditional least-squares (LS)-based curve fitting method
      for Cole parameter extraction is often sensitive to noise or outliers and becomes
      non-robust. This paper proposes an improved Cole parameter extraction based on
      the least absolute deviation (LAD) method. Comprehensive simulation experiments
      are carried out and the performances of the LAD method are compared with those of
      the LS method under the conditions of outliers, random noises and both
      disturbances. The proposed LAD method exhibits much better robustness under all
      circumstances, which demonstrates that the LAD method is deserving as an improved
      alternative to the LS method for Cole parameter extraction for its robustness to
      outliers and noises. 

PMID- 24021748
TI  - Predictors of favourable outcome in inflammatory Crohn's disease. A retrospective
      observational study.
AB  - BACKGROUND: No studies have specifically searched for predictors of a favourable
      outcome that would allow a conservative therapeutic approach in adult Crohn's
      disease (CD). AIMS: To identify predictors of a favourable disease course over
      time at CD diagnosis. METHODS: We identified and included all patients diagnosed
      with CD between January 1994 and December 2003, who had CD with an inflammatory
      pattern and no perianal disease at diagnosis, and who were followed up for at
      least 5 years. Clinical and therapeutic features until December 2008 and losses
      to follow-up were identified. We defined a favourable outcome as the absence of
      stricturing and penetrating complications of the disease (including perianal
      disease), together with the absence of need for anti-TNF therapy or resectional
      surgery during follow up. RESULTS: One hundred and forty-five patients were
      included and followed up for a median of 96 months (IQR, 79-140). At diagnosis,
      location was ileal in 39%, colonic in 28%, and ileocolonic in 32%; 50% of the
      patients were active smokers, and 41% used immunomodulators. Eighty-two patients
      (57%) met the criteria for a favourable outcome at the end of follow-up. The only
      factor associated with a favourable outcome was isolated colonic involvement
      (P=0.022), with 73% of these patients meeting the criteria for a favourable
      outcome. CONCLUSIONS: A favourable outcome of initially uncomplicated CD is not
      easily predicted at disease diagnosis by means of clinical or epidemiologic
      factors. Nevertheless, patients with isolated colonic disease are less likely to
      have an aggressive course.

PMID- 24021746
TI  - Childhood cancer and traffic-related air pollution exposure in pregnancy and
      early life.
AB  - BACKGROUND: The literature on traffic-related air pollution and childhood cancers
      is inconclusive, and little is known on rarer cancer types. OBJECTIVES: We sought
      to examine associations between childhood cancers and traffic-related pollution
      exposure. METHODS: The present study included children < 6 years of age
      identified in the California Cancer Registry (born 1998-2007) who could be linked
      to a California birth certificate (n = 3,590). Controls were selected at random
      from California birthrolls (n = 80,224). CAlifornia LINE Source Dispersion
      Modeling, version 4 (CALINE4) was used to generate estimates of local traffic
      exposures for each trimester of pregnancy and in the first year of life at the
      address indicated on the birth certificate. We checked our findings by
      additionally examining associations with particulate matter (<= 2.5 MUm in
      aerodynamic diameter; PM2.5) pollution measured by community-based air pollution
      monitors, and with a simple measure of traffic density. RESULTS: With
      unconditional logistic regression, a per interquartile range increase in exposure
      to traffic-related pollution during the first trimester (0.0538 ppm carbon
      monoxide, estimated using CALINE4) was associated with acute lymphoblastic
      leukemia [ALL; first trimester odds ratio (OR) = 1.05; 95% CI: 1.01, 1.10]; germ
      cell tumors (OR = 1.16; 95% CI: 1.04, 1.29), particularly teratomas (OR = 1.26;
      95% CI: 1.12, 1.41); and retinoblastoma (OR = 1.11; 95% CI: 1.01, 1.21),
      particularly bilateral retinoblastoma (OR = 1.16; 95% CI: 1.02, 1.33).
      Retinoblastoma was also associated with average PM2.5 concentrations during
      pregnancy, and ALL and teratomas were associated with traffic density near the
      child's residence at birth. CONCLUSIONS: We estimated weak associations between
      early exposure to traffic pollution and several childhood cancers. Because this
      is the first study to report on traffic pollution in relation to retinoblastoma
      or germ cell tumors, and both cancers are rare, these findings require
      replication in other studies.

PMID- 24021749
TI  - [Ischemic duodenitis in a patient with multiple comorbidities].

PMID- 24021750
TI  - Impact of non-steroidal anti-inflammatory drugs on gastrointestinal cancers:
      current state-of-the science.
AB  - Growing evidence from epidemiologic and preclinical studies suggests that
      nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of gastrointestinal
      (GI) cancers, including esophageal, gastric, pancreatic, colorectal cancer, and
      hepatocellular carcinoma. However, there is also evidence indicating the absence
      of this benefit. The exact mechanism of NSAIDs' action on GI tumors is not known.
      Although some studies have suggested inhibition of carcinogenesis by NSAIDs
      through suppression effect on inflammation-associated cyclooxygenase-2 (COX-2)
      expression, other studies have suggested COX-2-independent mechanisms. Herein, we
      summarize the current state of-the-science regarding NSAID benefit for patients
      with GI cancers. 

PMID- 24021751
TI  - The efficacy of on-site evaluation for identification of transplant pancreas.
AB  - OBJECTIVE: Pancreatic transplantation has been relatively uncommon until the last
      2 decades, but is now an accepted therapeutic intervention for type I diabetes.
      Core biopsies of pancreas transplants are frequently performed to rule out
      rejection, which is a leading cause of graft failure. Often, it is difficult to
      localize the graft for biopsy by imaging. Our objective was to determine whether
      on-site assessment by cytopathology can assist in procedure protocols for biopsy
      of pancreas transplants. STUDY DESIGN: We reviewed cytology and surgical
      pathology reports from 68 instances of pancreas transplant biopsy at our
      institution and evaluated the correlation between cytology (fine needle
      aspiration, touch preparation or both) and the final core biopsy. RESULTS:
      Pancreatic tissue was identified by on-site assessment in 56/68 cases and was
      present on core biopsy in 53/68 cases. There were 3 cases where fine needle
      aspiration/touch preparation results were not concordant with final core biopsy
      results. The positive predictive value of a positive on-site assessment was
      96.4%. More importantly, the negative predictive value of on-site assessment was
      100%. CONCLUSIONS: On-site evaluation by cytopathology is highly effective for
      the identification of transplant pancreas. In cases where no pancreatic tissue is
      identified by on-site assessment, relocalization of the biopsy needle is
      recommended.

PMID- 24021752
TI  - Evaluation of plasma trace element and mineral status in children and adolescents
      with phenylketonuria using data from inductively-coupled-plasma atomic emission
      and mass spectrometric analysis.
AB  - BACKGROUND: Phenylketonuria (PKU) is caused by a severe phenylalanine hydroxylase
      deficiency; the mainstay of treatment is a low-phenylalanine diet. A diet which
      is so restrictive is associated with a risk of nutritional deficiencies. We
      investigated plasma concentrations for 46 elements, including minerals and trace
      elements. METHODS: We enrolled 20 children and adolescents with PKU and 20
      matched controls. Multi-elementary quantification was carried out by solution
      based inductively coupled plasma atomic emission spectroscopy (ICP-AES) and ICP
      mass spectrometry (ICP-MS). RESULTS: With the exception of manganese and
      aluminium, no significant differences were found for element levels between PKU
      patients and controls. As a trend, manganese levels were lower in PKU patients
      than in control subjects (p < 0.05) but were within the reference range. There
      was a positive linear relationship between manganese and tyrosine levels in
      subjects with PKU (r(2) = 0.2295, p < 0.05). If detectable, potentially toxic
      elements were only identified in ultra-trace quantities in plasma samples of
      either group; aluminium levels were found to be slightly higher in PKU subjects
      than in controls (p < 0.01). CONCLUSION: The combination of ICP-AES and ICP-MS
      data is a useful diagnostic tool for element quantification at a high analytical
      rate and for monitoring bio-element status, e.g. in patients on a restrictive
      diet.

PMID- 24021753
TI  - Analysis of the multi-segmental postural movement strategies utilized in bipedal,
      tandem and one-leg stance as quantified by a principal component decomposition of
      marker coordinates.
AB  - Postural control research describes ankle-, hip-, or multi-joint strategies as
      mechanisms to control upright posture. The objectives of this study were, first,
      development of an analysis technique facilitating a direct comparison of the
      structure of such multi-segment postural movement patterns between subjects;
      second, comparison of the complexity of postural movements between three stances
      of different difficulty levels; and third, investigation of between-subject
      differences in the structure of postural movements and of factors that may
      contribute to these differences. Twenty-nine subjects completed 100-s trials in
      bipedal (BP), tandem (TA) and one-leg stance (OL). Their postural movements were
      recorded using 28 reflective markers distributed over all body segments. These
      marker coordinates were interpreted as 84-dimensional posture vectors,
      normalized, concatenated from all subjects, and submitted to a principal
      component analysis (PCA) to extract principal movement components (PMs). The PMs
      were characterized by determining their relative contribution to the subject's
      entire postural movements and the smoothness of their time series. Four, eight,
      and nine PM were needed to represent 90% of the total variance in BP, TA, and OL,
      respectively, suggesting that increased task difficulty is associated with
      increased complexity of the movement structure. Different subjects utilized
      different combinations of PMs to control their posture. In several PMs, the
      relative contribution of a PM to a subject's overall postural movements
      correlated with the smoothness of the PM's time series, suggesting that
      utilization of specific postural PMs may depend on the subject's ability to
      control the PM's temporal evolution. 

PMID- 24021754
TI  - Kobophenol A enhances proliferation of human osteoblast-like cells with
      activation of the p38 pathway.
AB  - Bone cell proliferation, bone formation, and bone resorption are the main factors
      involved in the homeostasis of the bone mass. Osteoblast death is a problem
      experienced by postmenopause women. Herbal medicines have attracted considerable
      attention for use as a drug or a drug substitute in the treatment of bone-related
      diseases, such as osteoporosis. This study investigated the effects of kobophenol
      A on the proliferation in human osteoblast cells. Kobophenol A stimulated the
      proliferation of osteoblast cells by the increases in DNA synthesis and the
      enhancement of cell cycle progression. Kobophenol A stimulation induced the
      expression of the cyclin B1 and cyclin-dependent kinase 1 (CDK1). Treatment of
      osteoblast cells with p38 MAPK inhibitor SB203580 significantly inhibited
      kobophenol A-enhanced proliferation. In addition, kobophenol A induced
      phosphorylation of p38 MAPK. Treatment of osteoblast cells with kobophenol A
      resulted in improvement of ROS scavenging activity. Moreover, kobophenol A
      treatment up-regulated the Bcl-2 level, but down-regulated the level of Bax
      expression. We also demonstrate that kobophenol A increased alkaline phosphatase
      (ALP) activity after 2 days. Taken together, the results of this study reveal
      that kobophenol A has proliferative effects and enhances ALP activity in
      osteoblast cells and these findings provide insights into the development of a
      therapeutic approach of kobophenol A in the prevention of osteoporosis and other
      bone disorders.

PMID- 24021755
TI  - Intranasal curcumin and its evaluation in murine model of asthma.
AB  - Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been
      shown to have a wide variety of pharmacological activities including anti
      inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for
      its low systemic bioavailability and rapid metabolization through oral route and
      has limited its applications. Over the recent decades, the interest in intranasal
      delivery as a non-invasive route for drugs has increased as target tissue for
      drug delivery since nasal mucosa offers numerous benefits. In this study, we
      evaluated intranasal curcumin following its absorption through nasal mucosa by a
      sensitive and validated high-performance liquid chromatography (HPLC) method for
      the determination of intranasal curcumin in mouse blood plasma and lung tissue.
      Intranasal curcumin has been detected in plasma after 15 min to 3 h at
      pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by
      inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At
      considerably lower doses has proved better than standard drug disodium
      cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration
      and histamine release in mouse model of asthma. HPLC detection revealed that
      curcumin absorption in lungs has started after 30 min following intranasal
      administration and retained till 3h then declines. Present investigations suggest
      that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and
      detected in plasma and lungs both and suppressed airway inflammations at lower
      doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for
      pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present
      study may prove the possibility of curcumin as complementary medication in the
      development of nasal drops to prevent airway inflammations and
      bronchoconstrictions in asthma without any side effect.

PMID- 24021756
TI  - Management of urinary incontinence in women: summary of updated NICE guidance.

PMID- 24021757
TI  - Reversing multidrug resistance by intracellular delivery of Pluronic(r) P85
      unimers.
AB  - Pluronics have been demonstrated as excellent multidrug resistance (MDR) reversal
      agent in the form of unimers rather than micelles. However, the effective
      intracellular delivery of Pluronic((r)) unimers to MDR cancer cells still remains
      a big challenge. To address this issue, a mixed micellar system based mainly on
      the pH-sensitive copolymer of poly (L-histidine)-poly (D,L-lactide)
      polyethyleneglycol-poly (D,L-lactide)-poly (L-histidine) (PHis-PLA-PEG-PLA-PHis)
      and Pluronic((r)) F127, some of which was conjugated with folate, was constructed
      to intracellularly deliver the unimers of Pluronic((r)) P85 to MDR cells. The
      folate-mediated endosomal pH-sensitive mixed micelles (pHendoSM-P85/f) were
      prepared by a thin-film hydration method, by which Pluronic((r)) P85 unimers and
      doxorubicin (DOX) were incoporated into the mixed micelles. The incorporation of
      Pluronic((r)) P85 unimers was investigated by the surface tension test. The
      results indicated that the Pluronic((r)) P85 unimers probably first inserted into
      the binary mixed micelles and then formed a triple-component mixed micelles with
      Pluronic((r)) F127 and PHis-PLA-PEG-PLA-PHis as the loading content increased.
      Further analyzed with flow cytometry, confocal laser scanning microscopy (CLSM)
      and MTT assay, the micelles with inserted Pluronic((r)) P85 unimers demonstrated
      much more cellular uptake and higher cytotoxicity against MDR cells than the
      triple-component mixed micelles and plain Pluronic((r)) micelles. The enhanced
      MDR reversal effect was attributed to the successful intracellular delivery of
      Pluronic((r)) P85 unimers to the MDR cells, which was confirmed by the
      subcellular colocalization of Pluronic((r)) P85 unimers with mitochondria, the
      decreased ATP energy and mitochondrial membrane potential (MP) in the MCF-7/ADR
      cells. The pHendoSM-P85/f/DOX also demonstrated more dramatic antitumor
      efficiency and remarkable reduction of ATP energy in the MDR cells in tumors than
      the control formulations. The intracellular delivery of Pluronic((r)) P85 unimers
      to the MDR cells based on the targeted and endosomal pH triggerd release mixed
      micelles has been demonstrated as a promising approach to reverse MDR.

PMID- 24021758
TI  - Spatial gradients of chemotropic factors from immobilized patterns to guide
      axonal growth and regeneration.
AB  - In this study, we investigated the effect of varying localized concentration
      gradients of NGF and Sema3A on the axonal outgrowth of embryonic chick DRG
      explants and primary neurons in vitro. Immobilized 2D NGF or Sema3A micropatterns
      were produced using photolithography on tissue culture cover slips. Two distinct
      regions were identified: slow, with little or no change in concentration of
      chemotropic factor; and steep, with a transition from low to high. The direction
      of axonal outgrowth was defined as proximal or distal, with proximal growing
      towards the higher concentration of immobilized NGF/Sema3A and vice versa for
      distal. Axons grew preferentially in the proximal direction when explants were
      seeded onto steep NGF, and distally in response to steep Sema3A. On slow NGF, or
      on slow Sema3A there was no difference in the directional specificity of axonal
      outgrowth. DRG primary neurons seeded onto steep NGF migrated proximally, whereas
      neurons seeded onto slow NGF migrated in all directions. Conversely, neurons
      seeded onto steep or slow Sema3A did not extend any axons. Our 2D immobilized
      micropatterns of chemotropic factors show promise for further development of in
      vitro nerve tissue engineering studies.

PMID- 24021759
TI  - Capillary morphogenesis in PEG-collagen hydrogels.
AB  - A wide variety of hydrogels have been explored as 3D culture platforms and for
      applications in tissue engineering. Hydrogels formed from natural extracellular
      matrix (ECM) proteins readily support the formation of vasculature in vitro, but
      only a handful of hydrogels composed of synthetic materials have shown anything
      comparable. This relative lack of synthetic material options has hindered efforts
      to better understand how ECM cues direct vascularization. We developed a
      biosynthetic hydrogel consisting of polyethylene glycol diacrylamide conjugated
      to macromolecular type-I collagen. Through their acrylamide-based crosslinks,
      these materials allow for independent control of physical properties and bulk
      ligand concentration. These hydrogels exhibited hydrolytic stability, but the
      collagen component retained its susceptibility to enzymatic remodeling.
      Photoencapsulation of endothelial cells and fibroblasts within this hydrogel
      material and their subsequent co-culture led to the formation of capillary vessel
      like networks with well-defined hollow lumens. Capillary formation was prevented
      by inhibiting matrix metalloproteinase (MMP) activity, recapitulating the MMP
      dependence of vascularization observed in natural hydrogels. These findings
      validate the utility of this material platform to decipher how the ECM regulates
      capillary morphogenesis and to support the formation of vascularized tissue
      constructs for potential applications in regenerative medicine.

PMID- 24021760
TI  - Expanding room for tetrazine ligations in the in vivo chemistry toolbox.
AB  - There is tremendous interest in developing and refining methods to predictably
      perform chemical reactions within the framework of living systems. Here we review
      recent advances in applying tetrazine cycloadditions to live cell and in vivo
      chemistry. We highlight new syntheses of the tetrazine and dienophile precursors
      useful for in vivo studies. We briefly overview the use of this reaction in
      combination with unnatural amino acid technology and discuss applications
      involving the imaging of glycans on live cells. An emerging area is the use of
      tetrazine ligations for the development of in vivo imaging probes such as those
      used for positron emission tomography. We summarize recent applications involving
      tetrazine cycloadditions performed in live mice for pretargeted imaging of cancer
      cell biomarkers. 

PMID- 24021761
TI  - The controversial role of chemoradiation for patients with locally advanced
      pancreatic cancer.

PMID- 24021762
TI  - A comparison of migrants to, and women born in, urban Mongolia: demographic,
      reproductive, anthropometric and lifestyle characteristics.
AB  - BACKGROUND: Mongolia has experienced vast migration from rural to urban areas
      since the 1950s. We hypothesized that women migrating to Ulaanbaatar, the
      capital, would differ in factors related to future chronic disease risk compared
      with women who were born in Ulaanbaatar. METHODS: Premenopausal mothers (aged <44
      years) of children attending two schools (one in the city centre and one in the
      outskirts) in Ulaanbaatar were recruited for the study. During April and May
      2009, 420 women were interviewed about migration, reproductive history and
      lifestyle factors and anthropometric measurements were taken. RESULTS: Women born
      in (n=178) and outside (n=242) Ulaanbaatar were similar in education and marital
      status, but the latter appeared to have a more traditional lifestyle including
      being more likely to have lived as a nomadic herder (22.3% vs 5.6%; p<0.001) and
      to currently live in a traditional yurt or ger (40.1% vs 29.2%). Ever-use of
      hormonal contraception was more common in women born outside Ulaanbaatar (52.1%
      vs 38.2%; p=0.005) and their age at first live birth was older (26.0% vs 20.8%
      for >= 25 vs <25 years). Although the number of pregnancies was similar, the
      number of live births was greater for those born outside Ulaanbaatar (p=0.002).
      Women born in Ulaanbaatar were more likely to have smoked cigarettes (24.7% vs
      11.2%; p<0.001). Women born outside Ulaanbaatar were more likely to consume the
      traditional meat and dairy diet. CONCLUSION: Rural migrants to Mongolia's capital
      have retained a traditional lifestyle in some, but not all, respects. Internal
      migrant populations may provide the opportunity to assess the effect of changes
      in isolated risk factors for subsequent chronic disease.

PMID- 24021763
TI  - Unfairness sensitivity and social decision-making in individuals with alcohol
      dependence: a preliminary study.
AB  - BACKGROUND: Altruistic punishment is an evolutionary-based mechanism aimed at
      maximizing the probability of reciprocity in cooperative exchanges, through the
      deterrence of non-cooperators. In economic games, humans will often punish others
      for non-cooperation, even if this punishment is costly to the self. For instance,
      in the Ultimatum Game paradigm, people refuse offers considered as unfair even
      though they are disadvantaged financially by doing so. Here, we hypothesize that,
      due to an impulsive decision making style, individuals with alcoholism will
      display an heightened unfairness sensitivity that leads them to reject
      advantageous offers more frequently on the Ultimatum Game. METHODS: Thirty
      recently detoxified alcohol-dependent individuals and 30 matched healthy control
      participants performed the Ultimatum Game task, in which participants had to
      respond to take-it-or-leave-it offers ranging from fair to unfair and made by a
      fictive proposer. RESULTS: Alcohol-dependent participants decided to reject
      unfair offers more frequently during the Ultimatum Game, as compared to controls.
      CONCLUSIONS: In situations of social frustration or irritation, such as unfair
      Ultimatum Game offers, alcohol-dependent individuals may have more difficulty
      than controls regulating their emotional impulses, and respond aggressively or
      retributively (i.e., by rejecting the unfair offer).

PMID- 24021764
TI  - Polyethyleneimine-based transient gene expression processes for suspension
      adapted HEK-293E and CHO-DG44 cells.
AB  - Transient gene expression (TGE) from mammalian cells is an increasingly important
      tool for the rapid production of recombinant proteins for research applications
      in biochemistry, structural biology, and biomedicine. Here we review methods for
      the transfection of human embryo kidney (HEK-293) and Chinese hamster ovary (CHO)
      cells in suspension culture using the cationic polymer polyethylenimine (PEI) for
      gene delivery. 

PMID- 24021765
TI  - Prognostic role of positron emission tomography and high-resolution computed
      tomography in clinical stage IA lung adenocarcinoma.
AB  - BACKGROUND: This multicenter study aimed to validate the ability of (18)F
      fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) plus
      high-resolution computed tomography (HR-CT) to predict the malignant behavior and
      prognosis of early adenocarcinomas of the lung. METHODS: We calculated maximum
      standardized uptake values (maxSUV) from PET/CT images and ground-glass opacity
      (GGO) ratios on HR-CT images before complete surgical intervention in 610
      patients with clinical stage IA lung adenocarcinoma. Pathologic invasiveness and
      survival were compared with clinical factors and radiographic findings including
      the maxSUV, which was revised to correct for interinstitutional discrepancies
      that confer limitations upon multicenter PET studies. RESULTS: Analyses of
      receiver-operating characteristic curves revealed optimal maxSUV and GGO ratio
      cutoffs to predict recurrence of 2.9 and 25%, respectively. Both the maxSUV and
      GGO ratio reflected tumor invasiveness, nodal metastasis, recurrence, and patient
      survivals, and were significant prognostic factors for recurrence-free and cancer
      specific survivals on multivariate Cox analysis (all, p < 0.001). The combination
      of maxSUV and GGO ratio is a better predictor of malignant tumor grade than
      either alone. CONCLUSIONS: The combination of maxSUV and GGO ratio as well as
      each alone are important predictors of prognosis in patients with clinical stage
      IA adenocarcinoma of the lung and should be considered before selecting
      therapeutic strategies.

PMID- 24021766
TI  - Intermediate follow-up results from the multicenter engager European pivotal
      trial.
AB  - BACKGROUND: Optimal transcatheter aortic valve (TAVI) results require accurate
      valve positioning, including anatomically correct orientation and secure fixation
      within the aortic annulus, thereby potentially decreasing paravalvular
      regurgitation. The new Engager (Medtronic 3F Therapeutics, Santa Ana, CA)
      transapical valve system captures the native leaflets for sealing and allows for
      tactile feedback during valve placement. We report initial safety and performance
      outcomes of the Engager system through 6 months in patients with severe aortic
      valve stenosis at high risk for surgical aortic valve replacement. METHODS: An
      interim analysis was performed on the first 61 enrolled September 2011 through
      May 2012. Inclusion criteria comprised severe aortic stenosis, New York Heart
      Association functional class of II or greater, logistic European System for
      Cardiac Operative Risk Evaluation (EuroSCORE) of 20% or greater, or
      contraindication to surgical aortic valve replacement. The primary endpoint was
      all-cause mortality at 30 days. Patients were evaluated 24 to 48 hours post
      procedure, at hospital discharge, 30 days and 6 months. Follow-up is planned
      annually through five years. RESULTS: Baseline characteristics for the 61
      patients were mean age 81.9 +/- 4.4 years, 62.3% female, 88.5% New York Heart
      Association class III/IV, 52.5% coronary artery disease, and 54.2% extracardiac
      arteriopathy. For all of the attempted implantations (n = 60), the Engager
      prosthesis was positioned in the correct anatomic position without conversions to
      surgery, second valve implantation, device malposition, aortic annular rupture,
      or coronary obstruction. All-cause mortality was 9.9% at 30 days and 16.9% at 6
      months. The baseline mean aortic valve gradient was 43.7 +/- 16.7 mm Hg and 11.5
      +/- 5.0 mm Hg at 30 days, and showed similar reduction at 6 months (13.9 +/- 6.2
      mm Hg). There was no paravalvular regurgitation greater than mild through 6
      months. CONCLUSIONS: Early postoperative results support implantation success and
      valve safety. Analysis for 6 month outcomes shows stable hemodynamic performance
      and clinical outcome. (Transapical Implantation of the Medtronic Engager
      Transcatheter Aortic Valve Implantation System-the Engager European Pivotal
      Trial; NCT01348438).

PMID- 24021767
TI  - Tissue Doppler imaging predicts left ventricular reverse remodeling after surgery
      for mitral regurgitation.
AB  - BACKGROUND: Tissue Doppler imaging of systolic mitral annular velocity (Sm) has
      been shown to be able to detect early left ventricular (LV) dysfunction in the
      presence of chronic severe mitral regurgitation with normal left ventricular
      ejection fraction. We investigated the association of preoperative Sm with LV
      reverse remodeling after mitral valve surgery. METHODS: Patients with chronic
      severe organic mitral regurgitation exhibiting LV ejection fraction greater than
      60% were enrolled. The LV reverse remodeling was defined as changes of LV mass
      index of 20% or greater postoperatively. The primary endpoints were to compare
      the changes of LV mass index in relation to the tertile distribution of the Sm
      and evaluate predictive value of the Sm for LV reverse remodeling. RESULTS: In
      all, 169 patients were analyzed. The changes of LV mass index in the first
      tertile was 25% (11% to 37) compared with 34% (19% to 43%) in the second tertile
      and 34% (26% to 47%) in the third tertile (p = 0.003). On multivariate analysis,
      Sm was the only independent predictor of LV reverse remodeling (odds ratio 1.77,
      95% confidence interval: 1.30 to 2.40, p < 0.001). The optimal cutoff value
      measured by receiver-operating characteristic curve analysis was 7 cm/s of Sm
      (area under the curve 0.721, 95% confidence interval: 0.64 to 0.80, p < 0.001).
      CONCLUSIONS: In patients with severe mitral regurgitation exhibiting LV ejection
      fraction greater than 60%, surgery may be considered before the Sm is decreased
      below 7 cm/s to achieve favorable LV reverse remodeling.

PMID- 24021768
TI  - Differential tensile strength and collagen composition in ascending aortic
      aneurysms by aortic valve phenotype.
AB  - BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) predisposes patients to
      aortic dissection and has been associated with diminished tensile strength and
      disruption of collagen. Ascending thoracic aortic aneurysms arising in patients
      with bicuspid aortic valve (BAV) develop earlier than in those with tricuspid
      aortic valves (TAV) and have a different risk of dissection. The purpose of this
      study was to compare aortic wall tensile strength between BAV and TAV ATAAs and
      determine whether the collagen content of the ATAA wall is associated with
      tensile strength and valve phenotype. METHODS: Longitudinally and
      circumferentially oriented strips of ATAA tissue obtained during elective surgery
      were stretched to failure, and collagen content was estimated by hydroxyproline
      assay. Experimental stress-strain data were analyzed for failure strength and
      elastic mechanical variables: alpha, beta, and maximal tangential stiffness.
      RESULTS: The circumferential and longitudinal tensile strengths were higher for
      BAV ATAAs when compared with TAV ATAAs. The alpha and beta were lower for BAV
      ATAAs when compared with TAV ATAAs. The maximal tangential stiffness was higher
      for circumferential when compared with longitudinal orientation in both BAV and
      TAV ATAAs. The amount of hydroxyproline was equivalent in BAV and TAV ATAA
      specimens. Although there was a moderate correlation between the collagen content
      and tensile strength for TAV, this correlation is not present in BAV.
      CONCLUSIONS: The increased tensile strength and decreased values of alpha and
      beta in BAV ATAAs despite uniform collagen content between groups indicate that
      microstructural changes in collagen contribute to BAV-associated aortopathy.

PMID- 24021769
TI  - Surgical results of synchronous multiple primary lung cancers: similar to the
      stage-matched solitary primary lung cancers?
AB  - BACKGROUND: Treatment for synchronous multiple primary lung cancers (SMPLC)
      remains controversial. Some surgeons treat SMPLC like advanced lung cancer,
      whereas other surgeons treat SMPLC as separate primary lung cancers. In this
      study, survival of SMPLC patients and matched-stage solitary primary lung cancer
      (SPLC) patients after surgical treatment were compared. METHODS: Prospective
      medical records between 2001 and 2011 were retrospectively reviewed. RESULTS: A
      total of 1,995 patients underwent pulmonary resection for lung cancer in a
      tertiary referral center. Only 97 patients met the modified criteria of Martini
      and Melamed for SMPLC. The median follow-up time was 38.3 months. The 3-year and
      5-year overall survival rates were 83.1% and 69.6%, respectively. In the
      univariate analysis, males, smokers, and tumor size greater than 3 cm
      demonstrated significantly worse survival. After multivariate analysis, only
      tumor size (p = 0.018; hazard ratio 3.199) was identified as an independent
      predictor of survival. In addition, there was no significant difference in
      overall survival between the matched-stage SMPLC and SPLC without mediastinal
      lymph node involvement. Subgroup analysis in the multiple synchronous
      adenocarcinoma (n = 78) group demonstrated no significant difference between
      similar and different comprehensive histologic subtyping with respect to overall
      survival (61.3% versus 68.8%, p = 0.474). CONCLUSIONS: The surgical results for
      SMPLC were compatible and acceptable with those for SPLC even with similar
      histologic subtyping, instead of T4 or M1 stages in the current TNM
      classification system. Preoperatively, tumor size was the only independent
      prognostic factor for SMPLC with surgical intervention.

PMID- 24021770
TI  - Impact of different cannulation strategies on in-hospital outcomes of aortic arch
      surgery: a propensity-score analysis.
AB  - BACKGROUND: The impact of different cannulation strategies on outcomes of aortic
      arch surgery remains controversial. This retrospective study sought to evaluate
      central cannulation (ascending aorta, right axillary, and innominate artery)
      compared with femoral artery cannulation for aortic arch surgery, and to identify
      among preoperative and intraoperative variables the independent predictors of
      death and permanent neurologic dysfunction (PND) in aortic arch surgery. METHODS:
      All patients were operated through a median sternotomy using antegrade selective
      cerebral perfusion with moderate hypothermia as a method of brain protection.
      Treatment bias was addressed by use of propensity-score matching and multivariate
      regression analysis. Logistic regression models were used to identify the
      independent predictors of hospital mortality and PND. RESULTS: Of the 473
      patients undergoing aortic arch surgery, 273 (57.7%) underwent femoral
      cannulation (FC), and 200 (42.3%) underwent central cannulation (CC). The CC and
      FC cannulation were associated with similar risk of in-hospital death (absolute
      risk reduction [ARR]: 0.7%; p = 0.880) and PND (ARR:-2.6%, p = 0.361) in the
      overall cohort and after adjusting for propensity-based matching (ARR for
      hospital mortality: 2.2%, p = 0.589; ARR for PND: 3.4%, p = 0.271). Female gender
      (odds ratio [OR]:2.1, p = 0.030), type A acute dissection or intramural hematoma
      (OR: 2.2; p = 0.041), and CPB time (OR: 1.010/minute, p = 0.015) were independent
      predictors of in-hospital death. Female gender (OR: 2.4; p = 0.033), type A acute
      dissection or intramural hematoma (OR: 4.2; p = 0.005), and diabetes (OR: 6.6, p
      = 0.007) were independent predictors of PND. CONCLUSIONS: During aortic arch
      surgery, CC and FC are associated with a similar risk of postoperative death and
      PND. Type A acute aortic dissection and cardiopulmonary bypass time remain strong
      risk factors for mortality and PND.

PMID- 24021772
TI  - Acute type a dissection: impact of antegrade cerebral perfusion under moderate
      hypothermia.
AB  - BACKGROUND: The optimal method of arterial cannulation and circulation management
      for acute type A aortic dissection (type A) remains debated. Moderate hypothermic
      circulatory arrest (MHCA) and unilateral selective antegrade cerebral perfusion
      (uSACP) is effective in the elective setting. In this study, the impact of MHCA
      and uSACP on outcomes for type A repair was evaluated. METHODS: A retrospective
      review identified 346 patients who underwent type A repair under circulatory
      arrest, including 193 patients who had MHCA/uSACP. Measured outcomes included
      operative mortality, permanent neurologic deficit (PND) and temporary neurologic
      deficit, renal failure, and tracheostomy. Propensity-adjusted, multivariable
      logistic regression analysis was used to model adverse outcomes. RESULTS: The
      mean age of MHCA/uSACP patients was 56 years. The mean temperature during MHCA
      was 26.9 +/- 2.0 degrees C. Operative mortality for MHCA/SACP patients was 9.8%
      compared with 20.3% for the non-MHCA/SACP group (p < 0.01). Propensity score
      analysis found that MHCA/uSACP did not represent an adverse risk factor for
      mortality, temporary neurologic deficit, PND, renal failure, or the need for
      tracheostomy compared with non-MHCA/uSACP techniques. There was a 2.32-fold
      higher incidence of PND among patients who underwent cross-clamping of the
      dissected aorta during cooling before circulatory arrest (p < 0.05). CONCLUSIONS:
      Emergent type A repair can be accomplished with respectable operative risk using
      MHCA/uSACP. Cross-clamping the dissected aorta before MHCA increases the
      incidence of PND. These data suggest that MHCA/uSACP represents an effective
      circulation management strategy for patients undergoing repair of type A and
      obviates the need for deep hypothermic circulatory arrest.

PMID- 24021771
TI  - Survival prediction models for coronary intervention: strategic decision support.
AB  - BACKGROUND: For a given patient with coronary artery disease, it is uncertain
      which therapy, percutaneous coronary intervention (PCI) or coronary artery bypass
      grafting (CABG), maximizes long-term survival. Hence, we developed survival
      models for CABG and PCI using bare-metal stents (BMS) or drug-eluting stents
      (DES), programmed a decision-support tool, and identified its potential
      usefulness. METHODS: From 1995 to 2007, 23,182 patients underwent primary
      isolated CABG (n=13,114) or first-time PCI with BMS (n=6,964) or DES (n=3,104).
      Follow-up was 6.3+/-3.9 years. Survival models were developed independently for
      each therapy, then all factors appearing in any of the three models were forced
      into a final model for each. These were programmed into a decision-support tool.
      Predicted differences in 5-year survival for the same patient among the three
      therapies were calculated. RESULTS: Unadjusted survival was 96%, 86%, and 68% at
      1, 5, and 10 years after CABG, 94%, 83%, and 68% after BMS, and 95% and 84% (no
      10-year estimate) after DES, respectively. Risk factors for early and mid-term
      mortality were identified, leading to variable-rich (25 variables) prediction
      models. Patients most likely to experience a 5-year survival benefit from DES
      were those undergoing emergency revascularization for acute infarction, and
      patients most likely to benefit from CABG had extensive coronary artery disease
      and numerous comorbidities. CONCLUSIONS: Detailed prediction models for prognosis
      after PCI and CABG are useful for developing a clinically relevant, strategic
      decision-support tool that reveals who may experience a long-term survival
      benefit from each modality.

PMID- 24021773
TI  - Preoperative cross-matching in major head and neck surgery: a study of a
      department's current practice and eligibility for electronic cross-matching.
AB  - OBJECTIVE: The maximum surgical blood ordering schedule (MSBOS) has reduced but
      not eliminated the over-ordering and wastage of blood products. Electronic cross
      matching (ECM) may be a suitable alternative method to provide blood on demand in
      eligible cases. The purpose of this study was to assess the department's current
      blood ordering policy and to identify patients eligible for ECM. STUDY DESIGN:
      This was a retrospective observational study of 88 consecutive maxillofacial
      surgical oncology patients. RESULTS: A total of 383 units of blood were cross
      matched, of which 43% were not transfused. Of these, 38% were reallocated and 5%
      discarded. Of all cross-matched blood, 82% was eligible for ECM; 18% was not
      eligible, 6% because of the presence of antibodies and 12% because of lack of a
      second historical sample. CONCLUSIONS: ECM is recommended as a safe method for
      elective surgery. Blood can be provided on demand, reducing workload and costs
      for transfusion services and minimizing wastage.

PMID- 24021774
TI  - Is migraine a complicating factor for evidence-based therapy for masticatory
      myofascial pain? A case-control study.
AB  - OBJECTIVE: This study aimed to assess the response to conservative treatment of
      pain in patients diagnosed with masticatory myofascial pain (MMP) with or without
      migraine. STUDY DESIGN: A total of 61 patients were evaluated and divided into 2
      groups: Group 1 (G1), patients with MMP (n = 34); Group 2 (G2), patients with MMP
      and migraine (n = 27). Pain was assessed subjectively by visual analog scale
      (VAS) and objectively through masticatory muscle palpation at baseline and after
      3 treatment visits. Treatment included occlusal appliances, medication, and self
      care exercises. RESULTS: G2 reported greater discomfort subjectively and
      objectively at all evaluation visits; however, significant difference between
      groups was noted objectively only at baseline (P = .0052). Regardless of group,
      pain levels decreased significantly over time as measured by VAS analyses (G1 P =
      .0033; G2 P = .0031) and muscle palpation (G1 P < .0001; G2 P < .0001).
      CONCLUSIONS: Evidence-based therapy improved pain scores over time in MMP
      patients regardless of the presence of migraine.

PMID- 24021775
TI  - Alveolar distraction osteogenesis versus autogenous onlay bone graft for vertical
      augmentation of severely atrophied alveolar ridges after 12 years of long-term
      follow-up.
AB  - OBJECTIVE: The aim of this study was to evaluate alveolar distraction
      osteogenesis (ADO) and autogenous onlay bone graft (AOBG) procedures by comparing
      their long-term results and their ability to correct severe vertical alveolar
      defects for further rehabilitation. STUDY DESIGN: Fourteen patients treated with
      ADO and 28 patients treated with AOBG were included in this study. Radiographic
      measurements of alveolar bone heights over time and the implant survival and
      success were compared for the 2 groups. RESULTS: The vertical bone gain was 8.4
      +/- 2.6 mm for ADO and 6.5 +/- 2.3 mm for AOBG. After a mean follow-up period of
      7.1 years, there was no significant difference between the 2 groups regarding
      alveolar bone heights over time and implant survival and success (P > .05). The
      cumulative survival and success rates were 97.3%, 92.7% in the ADO group and
      94.1%, 90.2% in the AOBG group, respectively. CONCLUSION: Both ADO and AOBG may
      be reliable and effective for ridge augmentation procedures of severe vertical
      alveolar bone defects and subsequent dental rehabilitation using implants.

PMID- 24021776
TI  - Hyponatremia is an independent predictor of adverse clinical outcomes in
      hospitalized patients due to worsening heart failure.
AB  - BACKGROUND AND PURPOSE: Hyponatremia is common and is associated with poor in
      hospital outcomes in patients hospitalized with heart failure (HF). However, it
      is unknown whether hyponatremia is associated with long-term adverse outcomes.
      The purpose of this study was to clarify the characteristics, clinical status on
      admission, and management during hospitalization according to the serum sodium
      concentration on admission, and determine whether hyponatremia was associated
      with in-hospital as well as long-term outcomes in 1677 patients hospitalized with
      worsening HF on index hospitalization registered in the database of the Japanese
      Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). METHODS AND
      SUBJECTS: We studied the characteristics and in-hospital treatment in 1659
      patients hospitalized with worsening HF by using the JCARE-CARD database.
      Patients were divided into 2 groups according to serum sodium concentration on
      admission <135mEq/mL (n=176; 10.6%) or >=135mEq/mL (n=1483; 89.4%). RESULTS: The
      mean age was 70.7 years and 59.2% were male. Etiology was ischemic in 33.9% and
      mean left ventricular ejection fraction was 42.4%. After adjustment for
      covariates, hyponatremia was independently associated with in-hospital death
      [adjusted odds ratio (OR) 2.453, 95% confidence interval (CI) 1.265-4.755,
      p=0.008]. It was significantly associated also with adverse long-term (mean 2.1+/
      0.8 years) outcomes including all-cause death (OR 1.952, 95% CI 1.433-2.657),
      cardiac death (OR 2.053, 95% CI 1.413-2.983), and rehospitalization due to
      worsening HF (OR 1.488, 95% CI 1.134-1.953). CONCLUSIONS: Hyponatremia was
      independently associated with not only in-hospital but also long-term adverse
      outcomes in patients hospitalized with worsening HF.

PMID- 24021777
TI  - Evaluating aspects of online medication safety in long-term follow-up of 136
      Internet pharmacies: illegal rogue online pharmacies flourish and are long-lived.
AB  - BACKGROUND: A growing number of online pharmacies have been established
      worldwide. Among them are numerous illegal websites selling medicine without
      valid medical prescriptions or distributing substandard or counterfeit drugs.
      Only a limited number of studies have been published on Internet pharmacies with
      regard to patient safety, professionalism, long-term follow-up, and
      pharmaceutical legitimacy verification. OBJECTIVE: In this study, we selected,
      evaluated, and followed 136 Internet pharmacy websites aiming to identify
      indicators of professional online pharmacy service and online medication safety.
      METHODS: An Internet search was performed by simulating the needs of potential
      customers of online pharmacies. A total of 136 Internet pharmacy websites were
      assessed and followed for four years. According to the LegitScript database,
      relevant characteristics such as longevity, time of continuous operation,
      geographical location, displayed contact information, prescription requirement,
      medical information exchange, and pharmaceutical legitimacy verification were
      recorded and evaluated. RESULTS: The number of active Internet pharmacy websites
      decreased; 23 of 136 (16.9%) online pharmacies ceased operating within 12 months
      and only 67 monitored websites (49.3%) were accessible at the end of the four
      year observation period. However, not all operated continuously, as about one
      fifth (31/136) of all observed online pharmacy websites were inaccessible
      provisionally. Thus, only 56 (41.2%) Internet-based pharmacies were continuously
      operational. Thirty-one of the 136 online pharmacies (22.8%) had not provided any
      contact details, while only 59 (43.4%) displayed all necessary contact
      information on the website. We found that the declared physical location claims
      did not correspond to the area of domain registration (according to IP address)
      for most websites. Although the majority (120/136, 88.2%) of the examined
      Internet pharmacies distributed various prescription-only medicines, only 9
      (6.6%) requested prior medical prescriptions before purchase. Medical information
      exchange was generally ineffective as 52 sites (38.2%) did not require any
      medical information from patients. The product information about the medicines
      was generally (126/136, 92.6%) not displayed adequately, and the contents of the
      patient information leaflet were incomplete in most cases (104/136, 76.5%).
      Numerous online operators (60/136, 44.1%) were defined as rogue Internet
      pharmacies, but no legitimate Internet-based pharmacies were among them. One site
      (0.7%) was yet unverified, 23 (16.9%) were unapproved, while the remaining
      (52/136, 38.2%) websites were not available in the LegitScript database. Contrary
      to our prior assumptions, prescription or medical information requirement, or the
      indication of contact information on the website, does not seem to correlate with
      "rogue pharmacy" status using the LegitScript online pharmacy verification
      standards. Instead, long-term continuous operation strongly correlated (P<.001)
      with explicit illegal activity. CONCLUSIONS: Most Internet pharmacies in our
      study sample were illegal sites within the definition of "rogue" Internet
      pharmacy. These websites violate professional, legal, and ethical standards and
      endanger patient safety. This work shows evidence that online pharmacies that act
      illegally appear to have greater longevity than others, presumably because there
      is no compelling reason for frequent change in order to survive. We also found
      that one in five websites revived (closed down and reopened again within four
      years) and no-prescription sites with limited medicine and patient information
      are flourishing.

PMID- 24021778
TI  - Single-photon emission computed tomography appropriateness: does it matter for
      patient outcomes?

PMID- 24021779
TI  - Impact of appropriate use on the prognostic value of single-photon emission
      computed tomography myocardial perfusion imaging.
AB  - BACKGROUND: Appropriate use criteria (AUC) have been developed to aid in the
      optimal use of single-photon emission computed tomography (SPECT)-myocardial
      perfusion imaging (MPI), a technique that is a mainstay of risk assessment for
      ischemic heart disease. The impact of appropriate use on the prognostic value of
      SPECT-MPI is unknown. METHODS AND RESULTS: A prospective cohort study of 1511
      consecutive patients undergoing outpatient, community-based SPECT-MPI was
      conducted. Subjects were stratified on the basis of the 2009 AUC for SPECT-MPI
      into an appropriate or uncertain appropriateness group and an inappropriate
      group. Patients were prospectively followed up for 27+/-10 months for major
      adverse cardiac events of death, death or myocardial infarction, and cardiac
      death or myocardial infarction. In the entire cohort, the 167 subjects (11%) with
      an abnormal scan experienced significantly higher rates of major adverse cardiac
      events and coronary revascularization than those with normal MPI. Among the 823
      subjects (54.5%) whose MPIs were classified as appropriate (779, 51.6%) or
      uncertain (44, 2.9%), an abnormal scan predicted a multifold increase in the
      rates of death (9.2% versus 2.6%; hazard ratio, 3.1; P=0.004), death or
      myocardial infarction (11.8% versus 3.3%; hazard ratio, 3.3; P=0.001), cardiac
      death or myocardial infarction (6.7% versus 1.7%; hazard ratio, 3.7; P=0.006),
      and revascularization (24.7% versus 2.7%; hazard ratio, 11.4; P<0.001). Among the
      688 subjects (45.5%) with MPI classified as inappropriate, an abnormal MPI failed
      to predict major adverse cardiac events, although it was associated with a high
      revascularization rate. Furthermore, appropriate MPI use provided incremental
      prognostic value beyond myocardial perfusion and ejection fraction data.
      CONCLUSIONS: When performed for appropriate indications, SPECT-MPI continues to
      demonstrate high prognostic value. However, inappropriate use lacks effectiveness
      for risk stratification, further emphasizing the need for optimal patient
      selection for cardiac testing.

PMID- 24021780
TI  - Smoking cessation practices in Kuwaiti general dental clinics.
AB  - OBJECTIVES: This study aimed to determine the degree of involvement of general
      dental practitioners working in primary health care centers of the Ministry of
      Health (MOH) of Kuwait in tobacco cessation activities. SUBJECTS AND METHODS: A
      survey questionnaire composed of 48 structured multiple choice questions aimed at
      assessing practitioner knowledge, attitudes, perceived expectations, confidence,
      and perceived barriers preventing them from performing these activities was
      distributed to 150 general dentists working in MOH dental clinics. RESULTS: One
      hundred forty-five dentists responded to the survey questionnaire. Twelve (12%)
      surveyed practitioners always or almost always incorporated overall tobacco
      cessation activities into their practice. Forty-one (3%) of the respondents felt
      that they had excellent cessation knowledge. One (1%) felt barriers prohibited
      their performance of cessation activities. One hundred (76%) participants
      strongly agreed that there was an expectation for them to perform cessation
      activities in their clinics. Fourteen (10%) respondents felt very confident about
      their cessation counseling skills. CONCLUSIONS: Findings showed that smoking
      cessation practices are not performed on a routine basis in MOH dental clinics.
      Practitioner knowledge and confidence showed the most significant association
      with the performance of cessation activities.

PMID- 24021781
TI  - An examination of neuromuscular and metabolic fatigue thresholds.
AB  - This study examined the relationships among the physical working capacity at the
      fatigue threshold (PWCFT), the power outputs associated with the gas exchange
      threshold (PGET) and the respiratory compensation point (PRCP), and critical
      power (CP) to identify possible physiological mechanisms underlying the onset of
      neuromuscular fatigue. Ten participants (mean +/- SD age: 20 +/- 1 years)
      performed a maximal incremental cycle ergometer test to determine the PWCFT,
      PGET, and PRCP. CP was determined from the 3 min all-out test. The PWCFT (197 +/-
      55 W), PRCP (212 +/- 50 W), and CP (208 +/- 63 W) were significantly greater than
      the PGET (168 +/- 40 W), but there were no significant differences among the
      PWCFT, PRCP, and CP. All thresholds were significantly inter-4 (r = 0.794-0.958).
      The 17% greater estimates for the PWCFT than PGET were likely related to
      differences in the physiological mechanisms that underlie these fatigue
      thresholds, while the non-significant difference and high correlation between the
      PWCFT and the PRCP suggested that hyperkalemia may underlie both thresholds.
      Furthermore, it is possible that the 5% lower estimate of the PWCFT than CP could
      more accurately reflect the demarcation of the heavy from severe exercise
      intensity domains. 

PMID- 24021782
TI  - Application of chemokine CXC motif ligand 12 as a novel diagnostic marker in
      preoperative fine-needle aspiration biopsy for papillary thyroid carcinoma.
AB  - OBJECTIVES: A panel composed of three immunomarkers, cytokeratin 19, HBME-1 and
      galectin-3, is recommended for improving the accuracy of diagnosing papillary
      thyroid carcinoma (PTC), but the results are sometimes inconsistent and difficult
      to interpret. We used immunocytochemistry to assess the utility of chemokine CXC
      ligand 12 (CXCL12) as a novel diagnostic marker for PTC employing paraffin
      embedded cell blocks. METHODS: We analyzed the expression of CXCL12 using
      immunocytochemical staining in 82 cases of thyroid lesions (47 PTCs and 35
      thyroid lesions other than PTC). To determine the optimal cut-off value for the
      assessment of CXCL12 positivity, we used receiver operating characteristics
      (ROC). RESULTS: ROC curves showed that the optimum diagnostic cut-off was 10%
      (area under the curve 0.950, 95% confidence interval 0.891-1.008), with exclusive
      CXCL12 expression in PTC compared to other thyroid lesions (p < 0.001). In total,
      more than 90% of the PTCs were associated with CXCL12 immunohistochemical
      staining, while only up to 11.4% of thyroid lesions other than PTC were positive
      for CXCL12. The follicular variant PTC showed 90% CXCL12 expression compared to
      10.5% positivity in follicular neoplasm. CONCLUSION: Our findings indicate that
      CXCL12 may be an effective supplementary diagnostic marker for PTC in
      preoperative fine-needle aspiration cytology using the cell block method.

PMID- 24021783
TI  - Hospital arrival time and functional outcome after acute ischaemic stroke:
      results from the PREMIER study.
AB  - INTRODUCTION: Information regarding hospital arrival times after acute ischaemic
      stroke (AIS) has mainly been gathered from countries with specialised stroke
      units. Little data from emerging nations is available. We aim to identify factors
      associated with achieving hospital arrival times of less than 1, 3, and 6 hours,
      and analyse how arrival times are related to functional outcomes after AIS.
      METHODS: We analysed data from patients with AIS included in the PREMIER study
      (Primer Registro Mexicano de Isquemia Cerebral) which defined time from symptom
      onset to hospital arrival. The functional prognosis at 30 days and at 3, 6, and
      12 months was evaluated using the modified Rankin Scale. RESULTS: Among 1096
      patients with AIS, 61 (6%) arrived in <1 hour, 250 (23%) in <3 hours, and 464
      (42%) in <6 hours. The factors associated with very early (<1 hour) arrival were
      family history of ischemic heart disease and personal history of migraines; in <3
      hours: age 40-69 years, family history of hypertension, personal history of
      dyslipidaemia and ischaemic heart disease, and care in a private hospital; in <6
      hours: migraine, previous stroke, ischaemic heart disease, care in a private
      hospital, and family history of hypertension. Delayed hospital arrival was
      associated with lacunar stroke and alcoholism. Only 2.4% of patients underwent
      thrombolysis. Regardless of whether or not thrombolysis was performed, arrival
      time in <3 hours was associated with lower mortality at 3 and 6 months, and with
      fewer in-hospital complications. CONCLUSIONS: A high percentage of patients had
      short hospital arrival times; however, less than 3% underwent thrombolysis.
      Although many factors were associated with early hospital arrival, it is a
      priority to identify in-hospital barriers to performing thrombolysis.

PMID- 24021784
TI  - [Correlation of hepatitis B virus X antigen expression with liver cell
      apoptosis].
AB  - OBJECTIVE: To study the roles of hepatitis B virus (HBV) X antigen (HBxAg) in
      development of HBV-related liver diseases and carcinogenesis. METHODS: Liver
      tissues were collected from patients with HBV infection (HBV carriers, n = 14;
      chronic hepatitis B (CHB), n = 24), HBV-related liver cirrhosis (LC, n = 20), or
      hepatocellular carcinoma (HCC, n = 20). Immunohistochemistry was used to detect
      the expression of HBxAg and the host apoptosis-related genes Fas and Fas ligand
      (Fas-L). The correlations of HBxAg with HBV DNA level in serum, inflammation
      grade, and fibrosis stage were statistically analyzed. Liver inflammation grade
      and fibrosis stage were in accordance with Knodell standard. x2test and Fisher's
      exact test were adopted in count data, x2split method was adopted in pariwise
      comparisons between multiple samples, Rank-sum test was adopted in ranked data,
      Spearman rank correlation analysis was adopted in correlation analysis. RESULTS:
      The rates of HBxAg-positivity were similar between the patients with HBV
      infection (71.1%), LC (60.0%), and HCC (65.0%) (x2= 0.754, P = 0.686). The rates
      of Fas- and Fas-L-positivity in liver cells were also similar between the three
      groups (Fas: 28.9% vs. 20.0% vs. 5.0%, x2= 4.667, P = 0.101; Fas-L: 36.8% vs.
      50.0% vs. 60.0%, x2= 2.988, P = 0.225). However, the positive rate of Fas in
      lymphocytes of liver tissue was significantly higher in the HCC patients than in
      the HBV-infected patients (90.0% vs. 68.4%, Z = -4.360, P = 0.00001). The
      expressions of HBxAg and Fas-L corresponded to regions of severe inflammation in
      tissues from LC patients and some HCC patients. Furthermore, the expression of
      HBxAg was positively correlated with Fas (r = 0.304, P = 0.02) and Fas-L (r =
      0.368, P = 0.004) in the HBV-infected patients and LC patients, and the
      expression of Fas was positively correlated with that of Fas-L (r = 0.448, P =
      0.0004). Patients with high and medium loads of HBV DNA showed significantly
      higher rates of HBxAg-positivity than those with low loads (88.9% and 69.2% vs.
      26.7%, P less than 0.05). CONCLUSION: In the early stage of chronic HBV
      infection, HBxAg may induce liver cell apoptosis by up-regulating Fas expression,
      and in the later stage, HBxAg may induce immune escape by up-regulating Fas-L
      expression in liver cells. Together, HBxAg and high HBV DNA load may promote
      chronic HBV infection and progression to hepatocarcinogenesis.

PMID- 24021785
TI  - [Clinical features of antiviral therapy-induced thyroid disease in patients with
      chronic hepatitis C].
AB  - OBJECTIVE: To investigate the clinical features of thyroid disease occurring in
      response to antiviral therapy in patients with chronic hepatitis C (CHC).
      METHODS: Eighty-two patients diagnosed with CHC were recruited for study from our
      hospital between 2009 and 2010. All patients were given a 48-week course of
      antiviral combination therapy with pegylated-interferon (Peg-IFN; 180 mug qw ih)
      and ribavirin (RBV; 15 mg/kg bw). Patient sera was collected prior to treatment
      (baseline), at treatment weeks 24 and 48, and post-treatment week 24, and used to
      detect changes in levels of thyroid function markers, thyroid-specific and other
      autoantibodies, complement factors, and immunoglobulins (Igs). Differential
      expression of biomarkers was assessed between patients who developed thyroid
      disorder and those who did not. RESULTS: At treatment week 48, 13.4% (11/82) of
      cases developed hypothyroidism, 3.7% (3/82) developed hyperthyroidism, 20.7%
      (17/82) tested positive for thyroglobulin antibody, and 22.0% (18/82) tested
      positive for thyroid peroxidase antibody. The patients who did not develop
      thyroid disease had significantly higher post-treatment levels (vs. baseline) of
      IgG (14.84 +/- 2.61 vs. 12.95 +/- 3.32 g/L, F = 10.458, P = 0.002) and C4 (0.26
      +/- 0.09 vs. 0.22 +/- 0.08 g/L, F = 6.835, P = 0.011) and significantly lower IgM
      (0.86 +/- 0.48 vs. 1.00 +/- 0.42 g/L, F = 9.106, P = 0.003). The patients who
      developed thyroid disease showed no significant differences in the baseline and
      post-treatment levels of IgG, C4, or IgM. When the two groups of patients who did
      or did not develop thyroid disease were compared, there was no difference in the
      amount of patients who achieved sustained virological response. CONCLUSION:
      Antiviral-induced thyroid disease in patients with refractory hepatitis C
      manifests as clinically-detectable abnormalities in serum levels of thyroid
      autoantibody and markers of hypothyroidism. Levels of other autoantibodies and
      Igs do not correlate with the development of thyroid disease in these patients,
      and thyroid disease does not appear to affect the efficacy of Peg-IFN + RBV
      antiviral therapy.

PMID- 24021786
TI  - [Effect of antiviral treatment on expression of programmed death 1 and programmed
      death ligand 1 on peripheral T lymphocytes in patients with chronic hepatitis C].
AB  - OBJECTIVE: To evaluate the changes in programmed death 1 (PD-1) and programmed
      death ligand 1 (PD-L1) expression on peripheral blood T lymphocytes of patients
      with chronic hepatitis C (CHC) over the 24 weeks course of antiviral therapy.
      METHODS: Twenty-four CHC patients administered 24 weeks of combination antiviral
      therapy with pegylated-interferon-alpha-2a (Peg-IFNa-2a) and ribavirin (RBV) were
      enrolled for study from the Nanjing Second Hospital between October 2008 and
      October 2011. Peripheral blood was collected before treatment initiation, at
      treatment weeks 4, 12 and 24, and post-treatment week 24 (to investigate
      sustained virologic response (SVR), and used to measure expression of PD-1 and PD
      L1 on CD4+ and CD8+ T lymphocytes by flow cytometry, load of serum hepatitis C
      virus (HCV) RNA by real-time polymerase chain reaction, and level of serum
      alanine aminotransferase (ALT) by auto-biochemical analyzer. Intergroup
      differences were analyzed by the two-sample t-test, and the significance of
      differences between pre- and post-treatment measurements was determined by one
      way or two-way repeated measurements analysis of variance tests. RESULTS: At
      treatment week 4, 19 of the CHC patients were HCV RNA-negative. Among those
      patients the PD-1 expression on both T lymphocyte subsets showed a significant
      decrease from pre-treatment to post-treatment week 24 (CD4+: 18.6 +/- 6.1% vs.
      10.3 +/- 7.7%, F = 12.406, P = 0.002; CD8+: 16.6 +/- 13.8% vs. 9.4 +/- 4.6%, F =
      4.955, P = 0.039). However, the CD8+ lymphocyte subset showed significant
      increase in PD-L1 expression during treatment (pre-treatment: 17.5 +/- 13.7% vs.
      treatment week 4: 25.9 +/- 11.1%, F = 9.063, P less than 0.01; 12: 29.6 +/-
      15.1%, F = 8.365, P less than 0.01; 24: 32.0 +/- 15.7%, F = 9.736, P less than
      0.01). Among the five CHC patients showing HCV RNA-positivity at treatment week 4
      there was only a significant difference observed in the increased expression of
      PD-L1 on CD8+ lymphocyte subset from pre-treatment to treatment week 24 (17.4 +/-
      16.7% vs. 39.2 +/- 15.6%, F = 10.292, P = 0.033). Twenty of the CHC patients
      achieved SVR. among whom the PD-1 expression was significantly decreased during
      treatment on the CD4+ lymphocyte subset (pre-treatment: 20.2 +/- 7.5% vs.
      treatment week 4: 14.4 +/- 7.5%, F = 6.133, P less than 0.05; 12: 14.0 +/- 6.9%,
      F = 5.541, P less than 0.05; 24: 10.7 +/- 7.6%, F = 14.780, P less than 0.05) and
      on the CD8+ lymphocyte subset (pre-treatment: 16.8 +/- 13.4% vs. treatment week
      12: 10.2 +/- 4.6%, F = 4.964, P less than 0.05; 24: 10.1 +/- 4.9%, F = 4.613, P
      less than 0.05). Additionally, the PD-L1 expression was significantly increased
      during treatment on the CD8+ lymphocyte subset (pre-treatment: 19.0 +/- 14.5% vs.
      treatment week 12: 30.8 +/- 16.6%, F = 6.442, P = 0.020; 24: 35.2 +/- 16.5%, F =
      12.349, P = 0.002). Among the four CHC patients who relapsed there were no
      significant differences observed in the expressions of PD-1 or PD-L1 on the CD4+
      or CD8+ T lymphocytes. CONCLUSION: The standard Peg-IFNa-2a + RBV combination
      antiviral therapy reduces PD-1 expression on CD4+ and CD8+ T lymphocytes and
      increases PD-L1 expression on CD8+ T lymphocytes in peripheral blood. The
      clinical outcome of CHC patients may be related to the antiviral therapy-induced
      changes in expressions of PD-1 and PD-L1 on T lymphocytes.

PMID- 24021787
TI  - [A retrospective follow-up study of prolonged nucleos(t)ide analogue and
      interferon combination therapy in HBeAg-positive chronic hepatitis B patients].
AB  - OBJECTIVE: To investigate the efficacy of a 96-week course of nucleos(t)ide
      analogue and interferon (IFN) combination therapy for achieving seroconversion at
      24 weeks after completion in patients with chronic hepatitis B (CHB). METHODS:
      One-hundred-and-thirty-five CHB patients with positivity for hepatitis B e
      antigen (HBeAg) were recruited for study between January 2005 and December 2008.
      All patients were given a 96-week course of nucleos(t)ide analogue (lamivudine or
      adefovir dipivoxil) alone (monotherapy controls, n = 45) or in combination with
      IFN or Pegylated-IFN-alpha-2a (Peg-IFNa-2a) (n = 90). At treatment weeks 12, 24,
      48, 72, and 96, and at 24 weeks after treatment completion, serum samples were
      collected from all patients for assessment of biochemical, virological and
      serological responses to treatment. The biochemical response was indicated by
      normalization of the alanine aminotransferase (ALT) level. The virologic response
      was indicated by a reduction in the hepatitis B virus (HBV) DNA level to less
      than 1000 copies/ml. The serological response was indicated by seroconversion of
      either HBeAg or hepatitis B surface antigen (HBsAg). Statistical analysis was
      performed with the Chi-squared test. RESULTS: Among the patients treated with
      nucleos(t)ide analogue and IFN combination therapy, 41.1% (37/90) achieved HBeAg
      seroconversion and 18.9% (17/90) achieved HBsAg seroconversion at the end of
      treatment. However, significantly less of the patients treated with nucleos(t)ide
      analogue monotherapy achieved HBeAg seroconversion and none achieved HBsAg
      seroconversion by end of treatment (33.3% and 0%, respectively; x2= 8.08, P less
      than 0.01 vs. the combination therapy group). Age stratification of the 17 HBsAg
      seroconverted patients treated with combination therapy indicated that the HBsAg
      seroconversion rate was significantly higher in patients less than 30-years-old
      than those 30 and older (x2= 12.62 and 4.24, respectively, P less than 0.05). At
      post-treatment week 24, the 17 HBsAg-seroconverted patients treated with
      combination therapy showed HBsAg titers of less than 250 IU/ml; moreover, 11.8%
      (2/17) of these patients remained HBeAg-positive and 17.6% (3/17) showed abnormal
      ALT levels and elevated HBV DNA. CONCLUSION: Prolonged nucleos(t)ide analogue
      plus IFN combination therapy can significantly improve the rate of HBsAg
      seroconversion in HBeAg-positive CHB patients, and this treatment regimen is
      especially efficacious in patients under the age of 30.

PMID- 24021788
TI  - [Application of a refined fibrosis staging system to evaluate therapeutic
      efficacy in chronic viral hepatitis].
AB  - OBJECTIVE: To generate a refined staging system of fibrosis in chronic viral
      hepatitis and to assess its accuracy and sensitivity for evaluating therapeutic
      efficacy of anti-fibrosis drug treatments. METHODS: A refined fibrosis staging
      system was established according to the detailed characteristics of progressive
      fibrosis. A total of 396 liver puncture biopsy specimens were collected from
      patients before and after anti-fibrosis therapy and used to evaluate the refined
      staging system. According to the original fibrosis staging system and refined
      fibrosis staging system, fibrosis staging differences from before and after
      treatment were analyzed by Chi-squared test and paired-samples t-test
      respectively. RESULTS: The refined fibrosis staging system detected significant
      changes in fibrosis stage that occurred in response to treatment (before
      treatment: 6.55 +/- 2.93 vs. after treatment: 6.19 +/- 2.945, P less than 0.01).
      However, the original (unrefined) staging system was unable to differentiate
      therapy-related changes in fibrosis stage (x2= 3.144, P = 0.534). CONCLUSION: The
      newly-developed refined fibrosis staging system was able to effectively evaluate
      the therapeutic efficacy of anti-fibrosis drug treatment and performed better
      than the original staging system.

PMID- 24021789
TI  - [Effects of cordyceps acid and cordycepin on the inflammatory and fibrogenic
      response of hepatic stellate cells].
AB  - OBJECTIVE: To investigate the effects of cordyceps acid and cordycepin on the
      inflammatory phenotype and fibrogenic property of hepatic stellate cells (HSCs).
      METHODS: An immortalized mouse HSC line (JS1) was stimulated with
      lippolysaccharide (LPS; 100 ng/ml) to induce an inflammatory response with or
      without co-administration of cordyceps acid or cordycepin in various
      concentrations (10, 50, or 200 mumol/L). Effects of the treatments on the
      chemokine monocyte chemotactic protein-1 (MCP-1) mRNA expression in the cells and
      the protein secretion in the cell culture supernatants were determined by reverse
      transcription and real-time quantitative PCR (RT-PCR) and enzyme-linked
      immunosorbent assay (ELISA), respectively. In addition, JS1 cells were treated
      with transforming growth factor-b1 (TGFb1; 10 ng/ml) to induce a fibrogenic
      response with or without co-administration of cordyceps acid or cordycepin in
      various concentrations (10, 50, or 200 mumol/L). Effects on the expression of
      fibrogenic proteins including collagen type I and a-smooth muscle actin (a-SMA),
      were investigated by Western blot. RESULTS: High-concentration (200 mumol/L)
      treatments of both cordyceps acid and cordycepin significantly inhibited the LPS
      induced up-regulation of MCP-1 transcription and secretion (mRNA: 2.07 +/- 0.29
      vs. 3.35 +/- 0.26, t = 15.90 and 1.15 +/- 0.23 vs. 4.17 +/- 0.61, t = 8.93;
      protein: 1.88 +/- 0.06 vs. 2.33 +/- 0.06, t = 10.39 and 1.47 +/- 0.25 vs. 1.97 +/
      0.04, t = 4.60; all P less than 0.05). All concentrations of cordyceps acid and
      cordycepin inhibited the TGFb1-induced up-regulation of collagen type I and a-SMA
      protein expression. However, the effects were more robust with the 200 mumol/L
      concentrations (P less than 0.05). CONCLUSION: Cordyceps acid and cordycepin
      ameliorate the LPS-induced inflammatory phenotype and TGFb1-induced fibrogenic
      response of cultured HSCs. These effects may contribute significantly to the
      drugs' therapeutic mechanisms to inhibit and resolve liver fibrosis.

PMID- 24021790
TI  - [Expression and roles of the epithelial mesenchymal transition markers E-cadherin
      and vimentin in hepatocellular carcinoma].
AB  - OBJECTIVE: To determine the differential protein expressions of epithelial
      mesenchymal transition (EMT) markers E-cadherin and vimentin in hepatocellular
      carcinorma (HCC) and to investigate their correlation to the molecular mechanisms
      of metastasis to explore their potential utility as prognostic indicators of HCC.
      METHODS: Tumor tissues and patient-matched adjacent non-tumor tissues were
      collected from individuals diagnosed with HCC. E-cadherin and vimentin protein
      expressions in the tissue specimens were quantified by western blot with
      densitometry of fluorescence emission and comparatively analyzed to determine the
      associations with molecular and clinical features. The expressions of E-cadherin
      and vimentin, as well as the other EMT-related protein Twist, were also detected
      in the tissue specimens by immunohistochemistry. Statistical analyses were
      carried out by paired-samples t-test, Mann-Whitney test, and Spearman rank
      correlation analysis. RESULTS: E-cadherin expression was significantly lower in
      tumor tissues (0.082 +/- 0.063 vs. adjacent non-tumor tissues: 0.226 +/- 0.215, t
      = -4.050, P less than 0.01), lower in patients with portal vein tumor thrombus
      (vs. non-thrombic HCC patients, P = 0.001), and correlated with TNM stage (III/IV
      > I/II, P = 0.003). Vimentin expression was significantly higher in tumor tissues
      (vs. adjacent non-tumor tissues, P = 0.002), negatively correlated with E
      cadherin expression (t = -0.509, P = 0.004), and closely associated with some
      clinical parameters, such as portal vein tumor thrombus (P less than 0.01), TNM
      stage (P less than 0.01), and Milan criteria (P = 0.005). Immunohistochemistry
      showed that E-cadherin expression was very weak in tumors but very strong in the
      cell membranes of non-tumor tissues, and that vimentin and Twist expressions were
      strong in tumors but undetectable in non-tumor tissue. CONCLUSION: Expression
      levels of the EMT markers E-cadherin and vimentin in HCC are related to clinical
      parameters, including portal vein tumor thrombus and TNM stage, and may represent
      useful prognostic markers of metastasis.

PMID- 24021791
TI  - [WISP-1: a novel mediator of hepatitis B virus-related hepatocellular carcinoma].
AB  - OBJECTIVE: To explore the effect of hepatitis B virus (HBV) X protein (HBX) on
      expression of the host gene Wnt induced secreted protein-1 (WISP-1) that is
      related to the pathogenic process of hepatocellular carcinoma (HCC). METHODS:
      Tumor and paratumor tissues were collected from HCC patients, and normal liver
      tissues were collected from healthy controls. Immunohistochemistry was used to
      evaluate the in vivo presence and expression levels of HBX and WISP-1 in the
      three tissue types. HepG2 cells stably transfected with pc-DNA3.1(+)-HBX or with
      pc-DNA3.1(+) only (G0, control) were generated and used to examine in vitro the
      HBX-induced changes in WISP-1 expression at the mRNA and protein levels by
      reverse transcription polymerase chain reaction and western blotting,
      respectively. RESULTS: The HCC tissues showed significantly higher rates of
      positivity for WISP-1 expression than the non-tumor controls (76.6% vs.
      paratumor: 23.4% or normal tissues: 0%, x2= 35.967, P less than 0.01). HBX
      increased WISP-1 expression in HepG2 cells at both the mRNA (1170.33 +/- 41.26
      vs. G0: 265.34 +/- 27.47, t = 31.63, P less than 0.01) and protein (240.33 +/-
      11.37 vs. G0: 40.33 +/- 7.09, F = 600.57, P less than 0.01) levels. CONCLUSION:
      HBV may up-regulate expression of the host gene WISP-1 through its X protein and
      thus promote the development of HCC.

PMID- 24021792
TI  - [Phosphorylation of eukaryotic initiation factor 2-alpha inhibits cisplatin
      mediated apoptosis of hepatocellular carcinoma cells].
AB  - OBJECTIVE: To investigate whether the phosphorylation (functionally inhibitive)
      of eukaryotic initiation factor 2-alpha (eIF2-a) affects the molecular mechanism
      of cisplatin-induced cellular apoptosis in human hepatocellular carcinoma (HCC).
      METHODS: The human HCC cultured cell lines SMMC-7221 and HepG2 were treated with
      cisplatin alone (controls; 24 h) or in combination with pre-transfection of a
      dominant-negative eIF2-a mutant (eIF2aS51A) or pre-exposure to an eIF2-a-specific
      phosphatase inhibitor (salubrinal) to decrease or increase the phosphorylation
      level, respectively. Changes in expression of apoptosis markers were
      quantitatively and qualitatively assessed by flow cytometry and western blot
      analysis. The significance of differences among groups was assessed by analysis
      of variance testing and of differences between groups was assessed by t-test.
      RESULTS: Cisplatin treatment induced the appropriate functional-inhibitive
      phosphorylation of eIF2-a on serine 51. Cisplatin treatment (10 mg/ml) induced
      significant apoptosis in the eIF2aS51A pre-transfected SMMC-7721 (control: 21.7
      +/- 1.5% vs. 50.7 +/- 2.1%, t = 19.454, P less than 0.05) and HepG2 (21.0 +/-
      1.0% vs. 57.3 +/- 2.1%, t = 27.250, P less than 0.05). Salubrinal pre-treatment
      significantly inhibited the cisplatin (15 mg/ml)-induced apoptosis in SMMC-7721
      (control: 50.3 +/- 2.5% vs. 16.3 +/- 2.1%, t = 18.031, P less than 0.05) and
      HepG2 (42.0 +/- 2.6% vs. 12.0 +/- 2.0%, t = 15.667, P less than 0.05).
      CONCLUSION: Phosphorylation of eIF2-a may act to inhibit cisplatin-induced
      apoptosis of HCC.

PMID- 24021793
TI  - [Clinical analysis of intrahepatic cholestasis of pregnancy].
AB  - OBJECTIVE: To generate a comprehensive clinical profile of intrahepatic
      cholestasis of pregnancy (ICP) by systematically reviewing ICP cases managed in
      our hospital. METHODS: The recorded clinical data, including diagnosis,
      complications, management, and maternal and infant outcomes, of nine ICP cases
      were collected retrospectively and reviewed systematically. RESULTS: Seven of the
      nine total ICP patients presented with pruritus. All nine of the ICP patients
      showed bile acid level beyond the normal range. ICP complications included
      gestational hypertension (n = 3), diabetes mellitus (DM, n = 1) and impaired
      glucose tolerance (IGT, n = 1), and pre-eclampsia (n = 1). The infant of one
      patient with severe ICP showed meconium-stained liquor. All nine of the ICP
      patients underwent surgical delivery, of which three were delivered preterm
      (between the 35th and 36th week of gestation). All mothers' total bile acids
      declined to normal levels after delivery, and all infants survived without
      complication. CONCLUSION: ICP does not increase the puerpera mortality rate and
      does not represent a poor prognosis for infants. Bile acid levels in the ICP
      patients, however, may be related to the extent of premature delivery time. While
      the standard drug treatment of ursodeoxycholic acid is suitable for most ICP
      cases, those with insufficient gestational age may benefit from adjuvant
      corticosteroid therapy to promote fetal lung maturation prior to preterm
      delivery. Severe ICP cases should be managed by inducing artificial labor or
      performing Caesarean section.

PMID- 24021794
TI  - [Investigate circulating levels of chemokines and evaluate the correlation
      between these chemokines and liver function indicators in autoimmune hepatitis].
AB  - OBJECTIVE: This study investigated circulation levels of chemokines (CCL2, CCL5,
      CXCL8, CXCL9, CXCL10) in autoimmune hepatitis(AIH) patients and evaluated the
      correlation between these chemokines and liver function indicators. METHODS: A
      total of 5 chemokines (CCL2, CCL5, CXCL8, CXCL9, CXCL10) were measured
      simultaneously by cytokine beads assay(CBA) in the sera of 46 patients with AIH
      and 12 cases of healthy control. RESULTS: In this study we found that serum
      levels of CCL2 , CXCL9 and CXCL10 in AIH patients and healthy controls were
      11.79:8.39 pg/ml, 11.31:2.69 pg/ml, 15.85:4.64 pg/ml, respectively , which
      implied these chemokines were significantly higher in AIH patients when compared
      to healthy control (Z=-1.958, P=0.05; Z=-4.527, P less than 0.0001; Z=-3.84, P
      less than 0.0001, respectively). And circulation levels of CCL2 , CXCL8 , CXCL9
      and CXCL10 in pretreatment and remission stages of patients with AIH were
      29.69:11.16 pg/ml, 7.2:5.38 pg/ml, 16.02:5.47 pg/ml, 90.01:13.24 pg/ml,
      respectively, which showed these chemokines decreased during remission from
      pretreatment stage levels (t=2.985, P=0.005; Z=-2.547, P=0.0112; Z=-3.187,
      P=0.001; t=2.12, P=0.0015, respectively). Among AIH , CXCL8 was correlated
      positively with lgG(r2=0.291, P=0.0039); CXCL9 was associated positively with ALT
      and AST(r2=0.5324 , P less than 0.0001; r2=0.3352, P less than 0.0001); CXCL10
      showed a positive correlation with ALT , AST and GGT(r2=0.9551, P less than
      0.0001; r2=0.8960, P less than 0.0001; r2=0.8271, P less than 0.0001).
      CONCLUSION: Serum levels of CCL2, CXCL8, CXCL9 and CXCL10 are significantly
      higher in patients with AIH, but decrease to levels in healthy controls after
      successful treatment , and circulation levels of CXCL9 and CXCL10 are associated
      positively with liver function indicators which can react inflammation activity
      of liver, all these may imply that chemokines can reflect the degree of liver
      inflammation and may be one of the main culprits in AIH pathological damage.

PMID- 24021795
TI  - [A diagnostic model for alcoholic liver disease based on a generalized regression
      neural network].
AB  - OBJECTIVE: To study the feasibility and rationale of using a generalized
      regression neural network model integrated with multiple disease indicators for
      diagnosing alcoholic liver disease (ALD). METHODS: ALD indicators were identified
      by reviewing the clinical testing results of 40 ALD patients from the literature
      and 135 patients from the Second Xiangya Hospital of Central South University,
      who were also classified by physician experts upon clinical consultation. Seven
      indicators were selected as diagnosis indexes and applied to a general regression
      neural network diagnostic model. Thirty-four of the reported patients and 120 of
      the clinical patients were selected for use as training samples to establish the
      indicator recognition pattern for the model, and the remaining six and 15
      patients from the two respective groups were selected for use as testing samples
      to determine the model's diagnostic ability. RESULTS: The model provided a
      correct diagnosis of ALD sub-classification for 94.1% (32/34) of the reported
      patients and 100% (120/120) of the clinical patients in the training set. The
      correct diagnosis rates achieved with the training sets were 100% for both the
      reported patient group (6/6) and the clinical patient group (15/15), indicating
      that the results of the diagnostic model were in good agreement with the ALD
      classifications generated by the clinical expert consultations. CONCLUSION: The
      general regression neural network model based on multiple indicators of ALD is
      capable of providing accurate and comprehensive diagnosis of ALD and may be
      feasible for clinical applications.

PMID- 24021796
TI  - [A novel treatment regimen for acute liver failure based on a combination of
      mesenchymal stem cells transplantation and IL-lRa-loaded chitosan nanoparticles].
AB  - OBJECTIVE: To evaluate whether a combination therapy using allogeneic mesenchymal
      stem cell (MSC) transplantation and interleukin-1 receptor antagonist (IL-1Ra)
      chitosan nanoparticles is more robust than MSC transplantation alone for treating
      acute liver failure and to investigate the mechanisms of the improved therapeutic
      effect using a swine model system. METHODS: IL-1Ra-loaded nanoparticles were made
      of lactosylated chitosan-FITC using the electrostatic spray method and analyzed
      by enzyme-linked immunosorbent assay. The active live targeting of these
      nanopaticles were investigated by fluorescence microscope and flow
      cytometer(FCM). The combined therapy was given and the Detailed Steps as follows:
      Chinese experimental mini swine were given D-galactosamine to build models of
      acute liver failure. Thirty-four pigs were randomly divided into five groups. In
      the control group(A),the normal saline was injected into liver via portal veins
      after 24 h; in IL-1Ra group(B), IL-1Ra was injected via ear veins 6 h before
      normal saline; In the MSCs transplantation group (C), 8 * 107 MSCs were injected
      into liver via portal veins after 24 h; IL-1Ra together with MSCs transplantation
      group(D) and nanopaticles group(E) as follows: on the one hand, 8 * 107 MSCs were
      injected into liver via portal veins after 24 h, on the other hand, rhIL-1Ra in
      group C or IL-1Ra chitosan nanopaticles in group D was injected via ear veins
      respectively at 6 h before. Liver function, serum inflammation and pathological
      changes were measured. The fate of MSCs was also observed. RESULTS: The profiles
      in vitro shown that there was a steady-state release after a fast linear release;
      The live targeting of the lactosylated chitosan-based nanoparticles was achieved
      by ligand-receptor specificity; The biochemical assay, the serum inflammation
      lever and pathological changes of the nanopaticles group were all greatly
      different from the other groups, the hepatocytes grow rate was significantly
      improved after 1 week; The liver engraftment was very low in group C and D with
      significantly higher numbers found in nanopaticles group, but the differentiation
      of MSCs after 2 weeks relatively rare; western blot showed that there was more
      HGF and VEGF secreted in nanopaticles group. CONCLUSION: IL-lRa-loaded
      lactosylated chitosan-based nanopaticles have significant liver targeting
      abilities and slow release characteristics in PBS solution. The combined therapy
      showed great synergistic effects through suppression of liver inflammation and
      paracrine.

PMID- 24021797
TI  - Surgical management of recurrent nasopharyngeal carcinoma.
AB  - OBJECTIVES: Nasopharyngeal carcinoma is a unique tumour which is endemic in
      Southern China including Hong Kong. While the treatment results for primary
      cancer has been encouraging, management of persistent or recurrent tumours has
      been challenging. Compared to other surgical approaches, the maxillary swing
      operation provides spacious access to the bilateral nasopharynx and the
      ipsilateral parapharyngeal space, allowing resection of tumours with wide
      margins. In this article, we will present our results in the surgical management
      of recurrent nasopharyngeal carcinoma. MATERIALS AND METHODS: Retrospective
      review. RESULTS: Over the years, we have performed salvage maxillary swing
      nasopharyngectomy for 312 patients. Microscopic negative resection margins were
      achieved in the majority (79.5%) of the patients. The overall local recurrence
      rate after surgery was 13.1%, the risk of which was significantly higher in
      patients with previous positive resection margins. The overall 5-year actuarial
      local tumour control and overall survival was 74% and 62%, respectively, which
      was significantly higher in patients with clear resection. For small tumours
      located in the posterior wall, minimally invasive approach can be used, which
      included the endoscopic resection, or more recently, the transoral robotic (TORS)
      assisted approach. CONCLUSION: The result of surgical salvage of recurrent
      nasopharyngeal carcinoma is promising. Every effort should be made to ensure
      microscopic clearance of disease as well as to minimize the potential
      complications of surgery that may adversely affect the subsequent quality of
      life.

PMID- 24021798
TI  - Spatial linear navigation: is vision necessary?
AB  - In order to analyze spatial linear navigation through a task of self-controlled
      reproduction, healthy participants were passively transported on a mobile robot
      at constant velocity, and then had to reproduce the imposed distance of 2-8m in
      two conditions: "with vision" and "without vision". Our hypothesis was that the
      reproduction of distances would be longer with than without visual information.
      Indeed, with visual information the reproduction of all distances was overshot.
      In the "without vision" condition the reproduced distances were quite close to
      the imposed ones, but only for the shortest distances (2 and 4m) as the longest
      ones were clearly undershot. With vision the reproduction error was less than 10%
      for all distances; however the error could be smaller without vision at short
      distances, and therefore vision was not necessary. 

PMID- 24021799
TI  - Manganese induces mitochondrial dynamics impairment and apoptotic cell death: a
      study in human Gli36 cells.
AB  - Manganese (Mn) is an essential trace element due to its participation in many
      physiological processes. However, overexposure to this metal leads to a
      neurological disorder known as Manganism whose clinical manifestations and
      molecular mechanisms resemble Parkinson's disease. Several lines of evidence
      implicate astrocytes as an early target of Mn neurotoxicity being the
      mitochondria the most affected organelles. The aim of this study was to
      investigate the possible mitochondrial dynamics alterations in Mn-exposed human
      astrocytes. Therefore, we employed Gli36 cells which express the astrocytic
      markers GFAP and S100B. We demonstrated that Mn triggers the mitochondrial
      apoptotic pathway revealed by increased Bax/Bcl-2 ratio, by the loss of
      mitochondrial membrane potential and by caspase-9 activation. This apoptotic
      program may be in turn responsible of caspase-3/7 activation, PARP-1 cleavage,
      chromatin condensation and fragmentation. In addition, we determined that Mn
      induces deregulation in mitochondria-shaping proteins (Opa-1, Mfn-2 and Drp-1)
      expression levels in parallel with the disruption of the mitochondrial network
      toward to an exacerbated fragmentation. Since mitochondrial dynamics is altered
      in several neurodegenerative diseases, these proteins could become future targets
      to be considered in Manganism treatment. 

PMID- 24021800
TI  - Dyrk1A-mediated phosphorylation of RCAN1 promotes the formation of insoluble
      RCAN1 aggregates.
AB  - The mechanisms underlying aggregate formation in age-related neurodegenerative
      diseases remain not well understood. Here we investigated whether dual
      specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A (Dyrk1A) is involved
      in the formation of regulator of calcineurin 1 (RCAN1) aggregates. We show that
      RCAN1 self-associates and forms multimers, and that this process is promoted by
      the Dyrk1A-mediated phosphorylation of RCAN1 at the Thr(192) residue. Transgenic
      mice that overexpress the Dyrk1A exhibited lower levels of phospho-Thr(192)-RCAN1
      in 10-month-old-group compared to littermate controls, when analyzed with soluble
      hippocampus lysates. These results suggest that the phosphorylation of RCAN1 by
      Dyrk1A stimulates the formation of insoluble aggregates upon aging. 

PMID- 24021801
TI  - Elevated levels of PPAR-gamma in the cerebrospinal fluid of patients with
      multiple sclerosis.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma), a ligand-activated
      transcriptional factor involved in the regulation of glucose and lipid
      metabolism, has gained interest as a potential therapeutic target in multiple
      sclerosis (MS) due to its potent immunoregulatory properties and the therapeutic
      efficacy of its ligands in experimental autoimmune encephalitis (EAE). Elevated
      expression of PPARgamma has been observed in the spinal cord of EAE mice and in
      an in vitro model of antigen-induced demyelination; however, no reports have yet
      been available on the PPARgamma status in the central nervous system of human
      individuals with MS. Aiming to identify a possible alteration, the present study
      assessed the levels of PPARgamma protein in the cerebrospinal fluid (CSF) of MS
      patients via ELISA technique. We report a pronounced elevation in the CSF levels
      of PPARgamma in MS patients (n=35) compared to non-inflammatory controls (n=22).
      This elevation was independent of blood-CSF barrier integrity, but correlated
      with CSF white blood cell count and IgG index, associating the observed elevation
      with neuroinflammation. Controlling for potential confounders, the CSF levels of
      PPARgamma further displayed a moderate but significant association with clinical
      severity. Corroborating with prior experimental findings, these results may
      contribute to our understanding about the role of PPARgamma in MS, and may
      implicate this protein as a potential CSF biomarker of the disease. 

PMID- 24021802
TI  - Desflurane accelerates neuronal cytotoxicity of Abeta by downregulating miR-214.
AB  - Since more and more evidence suggests anesthetics serve as a risk factor of
      Alzheimer's disease (AD), we examine the neurotoxicity of a commonly used
      inhalational anesthetics, desflurane, and its potential toxicity mechanism in
      primary rat hippocampal neurons. Here we show that desflurane increase the
      cytotoxicity of intracellular and extracellular amyloid beta (Abeta) in the
      presence or absence of serum. It is also demonstrated that the cytotoxicity of
      desflurane is caused by the reduction of miR-214 which binds to Bax 3'UTR and
      results in the increased expression of Bax. Therefore, we conclude that
      desflurane accelerates neuronal cytotoxicity of Abeta by downregulating miR-214.
      Our study sheds a light on the therapy of cytotoxicity induced by inhaled
      anesthetics, especially in patients of AD. 

PMID- 24021803
TI  - Effects of exogenous alpha-synuclein on stimulated dopamine overflow in dorsal
      striatum.
AB  - Alpha-synuclein (alpha-syn) is mainly a presynaptic protein that has been
      implicated in Parkinson's disease and various other neurodegenerative disorders.
      Evidence obtained in knockout mice suggests that alpha-syn controls plasticity of
      dopamine (DA) overflow in presynaptic terminals. It is also believed that alpha
      syn spreads and may seed its aggregates from cell to cell. The effects of
      exogenously applied alpha-syn on dopaminergic neurotransmission have not been
      studied. We addressed this issue by microinjecting human alpha-syn protein into
      the dorsal striatum of wild-type and alpha-syn knockout mice and monitoring
      stimulated DA overflow with constant potential amperometry. The evoked DA
      overflow was decreased in knockout mice six days after alpha-syn microinjection.
      The maximal velocity of DA re-uptake was reduced in both genotypes. Similar
      results were not seen when the effects of microinjected alpha-syn were studied
      immediately after the treatment, but instead there was a trend toward an increase
      in both stimulated DA overflow and maximal velocity of DA re-uptake. We conclude
      that locally applied human alpha-syn affects DA overflow and the effects depend
      on the presence of endogenous alpha-syn. 

PMID- 24021804
TI  - Effects of dual transcranial direct current stimulation on post-stroke unilateral
      visuospatial neglect.
AB  - Based on the interhemispheric inhibition model of unilateral visuospatial neglect
      (USN) after stroke, the effects of dual-mode transcranial direct current
      stimulation (tDCS) over the parietal cortices were assessed in a double-blind
      random-order cross-over experiment. Ten chronic right hemispheric stroke patients
      (4 men; mean age: 62.6 years) with USN were recruited. All participants underwent
      three randomly arranged tDCS sessions: (1) dual-mode, anodal tDCS over the right
      posterior parietal cortex (PPC) and cathodal tDCS over the left PPC; (2) single
      mode, anodal tDCS over the right PPC; and (3) sham mode. Each session lasted
      20min. Before and immediately after the stimulation, a line bisection test and
      star cancelation test were carried out. In the line bisection test, significant
      improvements were observed after both the dual- and the single-mode tDCS
      (p<0.05), but not after sham stimulation. Statistical analysis showed a
      significant interaction between time and tDCS mode, where the dual tDCS had a
      stronger effect than the single or sham stimulation modes (p<0.05). The star
      cancelation test did not show any significant change. These results suggest that
      dual tDCS over the bilateral PPC is an effective method for the treatment of USN
      in stroke patients. 

PMID- 24021805
TI  - Nongenomic, glucocorticoid receptor-mediated regulation of serotonin transporter
      cell surface expression in embryonic stem cell derived serotonergic neurons.
AB  - Depressive disorders have been linked to the combined dysregulation of the
      hypothalamus-pituitary-adrenal (HPA)-axis and the serotonergic system. The HPA
      axis and serotonergic (5-HT) neurons exert reciprocal regulatory actions. It has
      been reported that glucocorticoid-glucocorticoid receptor (GR) signaling
      influences serotonin transporter (5-HTT) transcription but data also points to
      the fact that 5-HTT expression is regulated nongenomically via redistribution of
      5-HTT from the cell surface into intracellular compartments. In order to analyze
      the acute effects of glucocorticoids on 5-HTT cell surface localization we
      differentiated serotonergic neurons from mouse embryonic stem (ES) cells derived
      from the C57BL/6N blastocysts. These postmitotic 5-HT neurons express all
      relevant serotonergic markers following the application of a growth factor-based
      differentiation protocol. Increasing concentrations of the GR agonist
      dexamethasone (Dex) resulted in enhanced, dose-dependent 5-HTT cell surface
      localization in the presence of the protein synthesis inhibitor cycloheximide
      already 1h after incubation. Inhibition of GR function by the specific GR
      antagonist mifepristone abolished the increase in 5-HTT cell surface
      localization. Hence, our data account for a nongenomic upregulation of 5-HTT cell
      surface expression by glucocorticoid-GR interaction which likely constitutes a
      rapid physiological response to increased levels of glucocorticoids as seen
      during stress. Taken together, we provide a cellular model to analyze and dissect
      glucocorticoid-5HTT interactions on a molecular level that corresponds to in vivo
      animal models using C57BL/6N mice. 

PMID- 24021806
TI  - Effects of voluntary alcohol drinking on corticotropin-releasing factor and
      preprodynorphin mRNA levels in the central amygdala of Sardinian alcohol
      preferring rats.
AB  - The stress-response corticotropin-releasing factor (CRF) and dynorphin systems
      are critically involved in alcohol drinking and "anxiety"-related behaviors.
      Selectively bred Sardinian alcohol-preferring (sP) rats display high inherent
      "anxiety"-related behaviors, in comparison with their alcohol-nonpreferring
      counterpart (sNP rats). The present study was undertaken to investigate: (1) if
      there were genetically determined differences in basal gene expression levels of
      CRF, CRF-R1, preprodynorphin (ppDyn) and kappa opioid receptor (KOP-r) between sP
      and sNP rats; specifically, mRNA levels of the above genes were measured in the
      central amygdala (CeA), hypothalamus and other stress responsive and mesolimbic
      regions of alcohol-naive sP and sNP rats; and (2) if the above mRNA levels were
      altered by voluntary alcohol drinking in sP rats exposed to the standard,
      homecage 2-bottle "alcohol vs. water" choice regimen 24h/day for 17 days. Higher
      basal CRF mRNA levels were found only in CeA of alcohol-naive sP rats, compared
      with sNP rats; these levels were decreased after alcohol consumption. In
      contrast, ppDyn mRNA levels in CeA of sP rats were increased by alcohol
      consumption, but with no basal difference from sNP rats. Although higher basal
      ppDyn mRNA levels were found in hypothalamus of sP rats, compared with sNP rats,
      there was no alteration after alcohol drinking in sP rats. No difference for the
      above mRNA levels was observed in other regions, including nucleus accumbens
      shell or core, caudate-putamen, ventral tegmental area and medial/basolateral
      amygdala, between the two rat lines before or after alcohol consumption. Our
      results demonstrate the existence of genetically determined high basal CRF mRNA
      levels in CeA of sP rats. Alcohol consumption decreased CeA CRF mRNA levels with
      parallel increases in CeA ppDyn mRNA levels. 

PMID- 24021807
TI  - ROCK mediates the inflammatory response in thrombin induced microglia.
AB  - To investigate whether the ROCK pathway is involved in thrombin-induced
      microglial inflammatory response, thrombin-induced microglia were pretreated with
      the thrombin inhibitor argatroban or a ROCK inhibitor Y-27632. Microglial
      inflammatory response was evaluated by phagocytosis of fluorescein labeled latex
      beads analyses and inflammatory mediators' expression such as nitric oxide (NO)
      and tumor necrosis factor-alpha (TNF-a). Compared to non-induced microglia,
      thrombin-induced microglia show significantly enhanced phagocytotic capacity and
      increased ROCK, NO and TNF-a expression. Pretreatment of thrombin-induced
      microglia with argatroban or Y-27632 significantly decreased phagocytotic
      capacity and reduced ROCK, NO and TNF-alpha expression. Therefore, the ROCK
      pathway may play a vital role in the mechanisms by which thrombin induces
      microglia in the inflammatory response. 

PMID- 24021808
TI  - Up-regulation of spinal microglial Iba-1 expression persists after resolution of
      neuropathic pain hypersensitivity.
AB  - Spinal microglial activation plays a major role in the development of neuropathic
      pain following peripheral nerve injury. We here provide evidence for an elevated
      expression of the microglial marker Iba-1 in the lumbar dorsal horn ipsilateral
      to L5 spinal nerve transection that persists for at least 14 weeks, a time at
      which mechanical hypersensitivity had fully resolved. Iba-1 expression was,
      however; significantly lower than at 4 weeks. We therefore conclude that
      microglia remain partly activated beyond the phase of pain hypersensitivity.
      Thus, the relation between microglial cells and neuropathic pain outcome is
      subject to change over time after nerve injury. 

PMID- 24021809
TI  - Literacy acquisition reduces the influence of automatic holistic processing of
      faces and houses.
AB  - Writing was invented too recently to have influenced the human genome.
      Consequently, reading acquisition must rely on partial recycling of pre-existing
      brain systems. Prior fMRI evidence showed that in literates a left-hemispheric
      visual region increases its activation to written strings relative to illiterates
      and reduces its response to faces. Increasing literacy also leads to a stronger
      right-hemispheric lateralization for faces. Here, we evaluated whether this
      reorganization of the brain's face system has behavioral consequences for the
      processing of non-linguistic visual stimuli. Three groups of adult illiterates,
      ex-illiterates and literates were tested with the sequential composite face
      paradigm that evaluates the automaticity with which faces are processed as
      wholes. Illiterates were consistently more holistic than participants with
      reading experience in dealing with faces. A second experiment replicated this
      effect with both faces and houses. Brain reorganization induced by literacy seems
      to reduce the influence of automatic holistic processing of faces and houses by
      enabling the use of a more analytic and flexible processing strategy, at least
      when holistic processing is detrimental to the task. 

PMID- 24021810
TI  - Valproic acid promotes neuronal differentiation by induction of neuroprogenitors
      in human bone-marrow mesenchymal stromal cells.
AB  - Recent studies have shown that the inhibition of histone deacetylases (HDACs)
      induces the differentiation of diverse cancer and stem cells, which suggests HDAC
      inhibitors may be good candidates for the induction of stem cell differentiation.
      In this study, we investigated the effects of a HDAC inhibitor, valproic acid
      (VPA), for the neuronal differentiation of human bone marrow-mesenchymal stromal
      cells (hBM-MSCs). VPA-treated MSCs had significant increases in their expression
      of the neuro-progenitor marker Nestin, Musashi, CD133, and GFAP, as measured by
      real-time PCR and immunoblot analysis. When VPA-pretreated MSCs were
      differentiated with neuronal induction media (VPA-dMSCs), they exhibited a cell
      body and dendritic morphology similar to neurons. The number and neurite length
      of these VPA-dMSCs significantly increased compared to differentiated MSCs
      (dMSCs). The VPA-dMSCs and dMSCs had significantly increased transcripts of
      neuronal-specific marker genes, including Nestin, Musashi, CD133, GFAP, NeuN, MAP
      2, NF-M, KCNH1, and KCNH5. The cells also showed a higher expression of the
      neuronal marker proteins Nestin and NF-M from immunocytochemical staining and
      immunoblot analysis. This study has shown that VPA pretreatment of hBM-MSCs,
      following their incubation with neuronal induction media, effectively stimulates
      neuronal cell differentiation to BM-MSCs. 

PMID- 24021811
TI  - Be prepared: enforcement of the new HIPAA rules.

PMID- 24021812
TI  - Cryo-EM structures of the actin:tropomyosin filament reveal the mechanism for the
      transition from C- to M-state.
AB  - Tropomyosin (Tm) is a key factor in the molecular mechanisms that regulate the
      binding of myosin motors to actin filaments (F-Actins) in most eukaryotic cells.
      This regulation is achieved by the azimuthal repositioning of Tm along the actin
      (Ac):Tm:troponin (Tn) thin filament to block or expose myosin binding sites on
      Ac. In striated muscle, including involuntary cardiac muscle, Tm regulates muscle
      contraction by coupling Ca(2+) binding to Tn with myosin binding to the thin
      filament. In smooth muscle, the switch is the posttranslational modification of
      the myosin. Depending on the activation state of Tn and the binding state of
      myosin, Tm can occupy the blocked, closed, or open position on Ac. Using native
      cryogenic 3DEM (three-dimensional electron microscopy), we have directly resolved
      and visualized cardiac and gizzard muscle Tm on filamentous Ac in the position
      that corresponds to the closed state. From the 8-A-resolution structure of the
      reconstituted Ac:Tm filament formed with gizzard-derived Tm, we discuss two
      possible mechanisms for the transition from closed to open state and describe the
      role Tm plays in blocking myosin tight binding in the closed-state position. 

PMID- 24021813
TI  - Dealing with transcriptional outbursts during S phase to protect genomic
      integrity.
AB  - Transcription during S phase needs to be spatially and temporally regulated to
      prevent collisions between the transcription and replication machineries. Cells
      have evolved a number of mechanisms to make both processes compatible under
      normal growth conditions. When conflict management fails, the head-on encounter
      between RNA and DNA polymerases results in genomic instability unless conflict
      resolution mechanisms are activated. Nevertheless, there are specific situations
      in which cells need to dramatically change their transcriptional landscape to
      adapt to environmental challenges. Signal transduction pathways, such as stress
      activated protein kinases (SAPKs), serve to regulate gene expression in response
      to environmental insults. Prototypical members of SAPKs are the yeast Hog1 and
      mammalian p38. In response to stress, p38/Hog1 SAPKs control transcription and
      also regulate cell cycle progression. When yeast cells are stressed during S
      phase, Hog1 promotes gene induction and, remarkably, also delays replication by
      directly affecting early origin firing and fork progression. Therefore, by
      delaying replication, Hog1 plays a key role in preventing conflicts between RNA
      and DNA polymerases. In this review, we focus on the genomic determinants and
      mechanisms that make compatible transcription with replication during S phase to
      prevent genomic instability, especially in response to environmental changes. 

PMID- 24021814
TI  - Crystal structure of the yeast ribosomal protein rpS3 in complex with its
      chaperone Yar1.
AB  - Eukaryotic ribosome assembly involves a plethora of factors, which ensure that a
      correctly folded ribosome contains all ribosomal protein components. Among these
      assembly factors, Yar1 has recently emerged as a molecular chaperone for
      ribosomal protein rpS3 of the small ribosomal subunit (40S) in yeast. In complex
      with its chaperone, rpS3 is imported into the nucleus and protected from
      aggregation. How rpS3 and other ribosomal proteins are initially sequestered and
      subsequently integrated into pre-ribosomal particles is currently poorly
      understood. Here, we present the crystal structure of yeast rpS3 in complex with
      its chaperone Yar1 at 2.8A resolution. The crystal structure rationalizes how
      Yar1 can protect rpS3 from aggregation while facilitating nuclear import and
      suggests a mechanism for a stepwise exchange of molecular partners that ribosomal
      proteins interact with during ribosome assembly. 

PMID- 24021815
TI  - Switching between the alternative structures and functions of a 2-Cys
      peroxiredoxin, by site-directed mutagenesis.
AB  - Members of the typical 2-Cys peroxiredoxin (Prx) subfamily represent an
      intriguing example of protein moonlighting behavior since this enzyme shifts
      function: indeed, upon chemical stimuli, such as oxidative stress, Prx undergoes
      a switch from peroxidase to molecular chaperone, associated to a change in
      quaternary structure from dimers/decamers to higher-molecular-weight (HMW)
      species. In order to detail the structural mechanism of this switch at molecular
      level, we have designed and expressed mutants of peroxiredoxin I from Schistosoma
      mansoni (SmPrxI) with constitutive HMW assembly and molecular chaperone activity.
      By a combination of X-ray crystallography, transmission electron microscopy and
      functional experiments, we defined the structural events responsible for the
      moonlighting behavior of 2-Cys Prx and we demonstrated that acidification is
      coupled to local structural variations localized at the active site and a change
      in oligomerization to HMW forms, similar to those induced by oxidative stress.
      Moreover, we suggest that the binding site of the unfolded polypeptide is at
      least in part contributed by the hydrophobic surface exposed by the unfolding of
      the active site. We also find an inverse correlation between the extent of ring
      stacking and molecular chaperone activity that is explained assuming that the
      binding occurs at the extremities of the nanotube, and the longer the nanotube
      is, the lesser the ratio binding sites/molecular mass is. 

PMID- 24021817
TI  - Age-dependent complex noise fluctuations in the brain.
AB  - We investigated the parameters of colored noise in EEG data of 17 722
      professional drivers aged 18-70. The whole study is based upon experiments
      showing that biological neural networks may operate in the vicinity of the
      critical point and that the balance between excitation and inhibition in the
      human brain is important for the transfer of information. This paper is devoted
      to the study of EEG power spectrum which can be described best by a power
      function with 1/f(lambda) distribution and colored noise corresponding to the
      critical point in the EEG signal has the value of lambda = 1 (purple noise). The
      slow accumulation of energy and its quick release is a universal property of the
      1/f distribution. The physiological mechanism causing energy dissipation in the
      brain seems to depend on the number and strength of the connections between
      clusters of neurons. With ageing, the number of connections between the neurons
      decreases. Learning ability and intellectual performance also decrease.
      Therefore, age-related changes in the lambda coefficient can be anticipated. We
      found that absolute values of lambda coefficients decrease significantly with
      increasing age. Deviations from this rule are related to age-dependent slowing of
      the dominant frequency in the alpha band. Age-dependent change in the parameter
      and colored noise may be indicative of age-related changes in the self
      organization of brain activity. Results obtained include (i) the age-dependent
      decrease of the absolute values of the average lambda coefficient with the
      regression coefficient 0.005 1/year, (ii) distribution of lambda value changes
      related to EEG frequency bands and to localization of electrodes on the scalp,
      and (iii) relation of age-dependent changes of colored noise and EEG energy in
      separate frequency bands. 

PMID- 24021818
TI  - Siblings exposed to intimate partner violence: linking sibling relationship
      quality & child adjustment problems.
AB  - Although the majority of families that experience intimate partner violence (IPV)
      have more than one child, most research to date has focused upon a single child
      within these families. A significant body of research has indicated siblings play
      an important role in children's adjustment and well-being. To address this gap,
      the three main goals of the present study were to compare the adjustment of older
      and younger siblings exposed to IPV, to describe and compare the quality of these
      sibling relationships from multiple perspectives, and to investigate how sibling
      adjustment and relationship quality influence children's adjustment. Forty-seven
      sibling pairs and their mothers were recruited from the community. Mothers self
      reported on their violent experiences using the Conflict Tactics Scale, and also
      estimated the length of time their children were exposed to IPV. Mothers and
      children completed assessments of child adjustment and the quality of sibling
      relationships. Observers also assessed the quality of sibling interaction.
      Results indicated that adjustment between siblings was highly inter-related. On
      average, mothers reported sibling relationships as less positive but also as less
      hostile than did siblings themselves. Higher levels of sibling hostility, lower
      levels of sibling warmth and higher levels of disengagement each significantly
      predicted child adjustment; however, these effects were predicated upon the
      adjustment of the other sibling. The sibling relationships of children exposed to
      IPV made a difference in their individual adjustment, and their adjustment issues
      influenced how they feel about and interacted with their sibling. Sibling
      hostility played a stronger role in adjustment issues than sibling warmth. The
      nature of sibling influences and the direction of future research were discussed.

PMID- 24021819
TI  - Effect of various conditions on inactivation of Escherichia coli O157:H7,
      Salmonella Typhimurium, and Listeria monocytogenes in fresh-cut lettuce using
      ultraviolet radiation.
AB  - The effect of various conditions on inactivation of foodborne pathogens and
      quality of fresh-cut lettuce during ultraviolet (254 nm, UVC) radiation was
      investigated. Lettuce was inoculated with a cocktail of Escherichia coli O157:H7,
      Salmonella Typhimurium, and Listeria monocytogenes and treated at different
      temperatures (4 and 25  degrees C), distances between sample and lamp (10 and 50
      cm), type of exposure (illuminated from one or two sides), UV intensities (1.36
      to 6.80 mW/cm2), and exposure times (0.5 to 10 min), sequentially. UV treatment
      at 25  degrees C for 1 min achieved 1.45-, 1.35-, and 2.12-log reductions in
      surface-inoculated E. coli O157:H7, S. Typhimurium, and L. monocytogenes,
      respectively, whereas the reduction of these pathogens at 4  degrees C was 0.31,
      0.57, and 1.16 log, respectively. UV radiation was most effective when distance
      from UV lamp to the sample was minimal (10 cm) and radiation area was maximal
      (two-sided exposure). All UV intensities significantly (P<0.05) reduced the three
      pathogens after 10 min exposure, but the effect of treatment was correlated with
      UV intensity and exposure time. Color values and texture parameters of lettuce
      subjected to UV treatment under the optimum conditions (25  degrees C, 10 cm
      between sample and lamp, two-sided exposure, 6.80 mW/cm2) were not significantly
      (P>0.05) different from those of nontreated samples up to 5 min exposure.
      However, these qualities significantly (P<0.05) changed at prolonged treatment
      time. These results suggest that UV radiation under optimized conditions could
      reduce foodborne pathogens without adversely affecting color quality properties
      of fresh-cut lettuce.

PMID- 24021816
TI  - Multiple C-terminal tails within a single E. coli SSB homotetramer coordinate DNA
      replication and repair.
AB  - Escherichia coli single-stranded DNA binding protein (SSB) plays essential roles
      in DNA replication, recombination and repair. SSB functions as a homotetramer
      with each subunit possessing a DNA binding domain (OB-fold) and an intrinsically
      disordered C-terminus, of which the last nine amino acids provide the site for
      interaction with at least a dozen other proteins that function in DNA metabolism.
      To examine how many C-termini are needed for SSB function, we engineered
      covalently linked forms of SSB that possess only one or two C-termini within a
      four-OB-fold "tetramer". Whereas E. coli expressing SSB with only two tails can
      survive, expression of a single-tailed SSB is dominant lethal. E. coli expressing
      only the two-tailed SSB recovers faster from exposure to DNA damaging agents but
      accumulates more mutations. A single-tailed SSB shows defects in coupled leading
      and lagging strand DNA replication and does not support replication restart in
      vitro. These deficiencies in vitro provide a plausible explanation for the
      lethality observed in vivo. These results indicate that a single SSB tetramer
      must interact simultaneously with multiple protein partners during some essential
      roles in genome maintenance. 

PMID- 24021820
TI  - Fate of E. coli O157:H7, Salmonella spp. and potential surrogate bacteria on
      apricot fruit, following exposure to UV-C light.
AB  - Some soft fruit, such as tree-ripened apricots, cannot be washed with aqueous
      sanitizers, due to their innate softness and delicate surfaces. In this study,
      ultraviolet-C (UV-C) light was investigated for its efficacy in inactivating 4-5
      individual strains of Escherichia coli O157:H7 and Salmonella spp. on apricots,
      in addition to a four-strain composite of Shiga toxin-negative E. coli O157:H7
      and a cocktail of three attenuated strains of Salmonella Typhimurium and
      Salmonella Typhimurium LT2. Also, the survival of E. coli O157:H7 and Salmonella
      spp. after exposure to 74 and 442 mJ/cm2 of UV-C was evaluated during post-UV
      storage at 2 and 20  degrees C. The fruit was spot inoculated and the areas (ca.
      1.5 cm2) of fruit surface with the inoculated bacteria were exposed to UV-C at
      7.4 mW/cm2. E. coli O157:H7 and Salmonella spp. populations decreased rapidly (1
      2 logs) (P<0.05) with increasing UV-C doses of 0 to 74 mJ/cm2. Further increases
      in UV-C dosage achieved only limited additional reductions in bacterial
      populations. Shiga toxin-negative bacteria and attenuated S. Typhimurium strains,
      along with S. Typhimurium LT2, responded similarly to corresponding pathogenic E.
      coli O157:H7 and Salmonella spp. During storage at 2 or 20  degrees C,
      populations of pathogenic E. coli O157:H7 and Salmonella spp. on untreated fruit
      decreased slowly; however, populations on fruit treated with 442 mJ/cm2 decreased
      rapidly at both temperatures. After 8 days at 20  degrees C or 21 days at 2 
      degrees C, E. coli O157:H7 and Salmonella spp. populations on UV-C treated fruit
      were at least 2 log CFU/g lower than on non-treated controls. Our results suggest
      that surface-inoculated bacteria survived poorly following UV-C treatment of
      apricots.

PMID- 24021821
TI  - Behavior of enteroaggregative Escherichia coli, non-O157-shiga toxin-producing E.
      coli, enteroinvasive E. coli, enteropathogenic E. coli and enterotoxigenic E.
      coli strains on mung bean seeds and sprout.
AB  - The behavior of enteroaggregative Escherichia coli (EAEC), non-O157 shiga toxin
      producing E. coli (non-O157-STEC), enteroinvasive E. coli (EIEC), enterotoxigenic
      E. coli (ETEC) and enteropathogenic E. coli (EPEC) on mung bean seeds at 25+/-2 
      degrees C and during germination and sprouting of mung bean seeds at 20+/-2 
      degrees  and 30+/-2  degrees C and on mung bean sprouts at 3+/-2  degrees C was
      determined. When mung bean seeds were inoculated with EAEC, non-O157 STEC, EIEC,
      EPEC or ETEC strains, all these diarrheagenic E. coli pathotypes (DEPs) survived
      at least 90 days on mung bean seeds at 25+/-2  degrees C. All DEPs grew during
      germination and sprouting of seeds, reaching counts of approximately 5 Log and 7
      Log CFU/g after 2 days at 20+/-2  degrees  and 30+/-2  degrees C, respectively.
      However, when the sprouts were inoculated after 1 day of seeds germination and
      stored at 20+/-2  degrees  or 30+/-2  degrees C, no growth was observed for any
      DEPs during sprouting at 20+/-2  degrees C per 9 d; however, a significant
      increase in the concentration of DEPs of approximately 0.7 log CFU/g was observed
      during sprouting at 30+/-2  degrees C after 1 day of sprout contamination.
      Refrigeration reduced the number of viable DEPs strains on sprouts after 10 days
      in storage; nevertheless, these decreases have no practical significance in the
      safety of the sprouts.

PMID- 24021822
TI  - Effect of high oxygen and high carbon dioxide atmosphere packaging on the
      microbial spoilage and shelf-life of fresh-cut honeydew melon.
AB  - This study evaluated the potential of modified atmospheres (MAs) combining high
      oxygen (O2) and high carbon dioxide (CO2) levels to extend the shelf-life of
      fresh-cut honeydew melon. Firstly, the effect of MA on the growth and volatile
      organic metabolite production of Candida sake, Leuconostoc mesenteroides and
      Leuconostoc gelidum, which had all been previously isolated from spoiled
      commercial fresh-cut honeydew melon, was evaluated separately on honeydew melon
      agar at 7  degrees C. Additionally, the effect of selected MAs on the microbial,
      physico-chemical and sensory quality of commercial fresh-cut honeydew melon cubes
      was evaluated at 7  degrees C. The results showed that MAs with high O2 and high
      CO2 levels greatly retarded the growth, CO2 and volatile metabolite production
      (i.e. ethanol, 2-methyl-1-butanol, ethyl acetate, phenylacetic acid, nonanal) of
      C. sake on honeydew melon agar; especially MAs consisting of 50% O2+50% CO2 and
      70% O2+30% CO2. In contrast, the MAs evaluated only had a minor effect on the
      growth and volatile metabolite production of L. mesenteroides and L. gelidum.
      Overall, the effect of MAs on colour, juice leakage, juiciness, and firmness of
      fresh-cut honeydew melon was small during storage. Sensory preference was
      generally for fresh-cut honeydew melon cubes packaged in MA of 50% O2+50% CO2.
      These were still acceptable on day five of storage and had appreciably lower
      populations of yeasts and lactic acid bacteria, lower quantities of volatile
      organic compounds, but slightly stronger colour oxidation compared to honeydew
      melon that was packaged in air. Additionally, most of the samples packed in air
      had blown by day five due to the large quantity of CO2 production during storage.
      Therefore, 50% O2+50% CO2 is a potential MA solution for extending the shelf-life
      of fresh-cut honeydew melon.

PMID- 24021823
TI  - [Recommendation for Sinupret as a supplementary specimen in pharmacological
      treatment of rhinosinusitis].
AB  - Due to rhinosinusitis symptoms severity and relatively high treatment resistance,
      excipients, supplementing basic pharmacological and surgical treatment, have
      played a significant role in the recent years. Phytotherapy is one of the most
      dynamically developing studies which focuses on implementing natural active
      substances into the treatment. 2012 EPOS Report pinpoints the benefits of using
      substances of natural origin in patients with acute rhinosinusitis. Sinupret drug
      has been proven effective in clinical trials, as a drug for both acute and
      chronic rhinosinusitis, in children and adults. Sinupret is a multidirectional
      drug, which significantly alleviates the symptoms of rhinosinusitis. 

PMID- 24021824
TI  - [Influence of complex deacon-tetra (N1,3-triazole,kN2) copper (II) on the barrier
      and antioxidant pro people with nasal polyps].
AB  - INTRODUCTION: The aim of this study was synthesized properties 1,2,4-triazole
      complex ion Cu (II) to determine their potential antioxidant properties, further
      indication of activity of antioxidant enzymes: catalase (CAT), glutathione
      peroxidase (GPX) and superoxide dismutase (Cu-Zn SOD) in patients with nasal
      polyps and the control group. MATERIAL AND METHODS: The study was conducted in a
      group of 30 patients with nasal polyps aged 48+/-13.50 (test 1 - group with a
      compound, test 2 - no relation), and 30 in the control group aged 48+/-17.90
      (control 3 - group with a compound, control 4 - no relation). Blood samples were
      collected from the antecubital vein into tubes with anticoagulant (heparin
      sodium). The activity of catalase, superoxide dismutase and glutathione
      peroxidase were determined in erythrocytes of patients with nasal polyps and the
      control group (those without inflammatory conditions. RESULTS: We found that
      patients with nasal polyps show a decrease in the activity of antioxidant enzymes
      compared to control: CAT (control 3 - 13.78+/-6.71 BU/gHb; test 1 - 8.52+/-7.96
      BU/gHb), SOD (control 3 - 1377,614.93+/-93.44 U/gHb/100ml; test 1 - 867,270.59+/
      49 U/gHb/100ml) and GPX (control 3 - 101.62+/-8.23 U/gHb; test 1 - 72.97+/-14.34
      U/gHb). Simultaneously, we observed that increasing the activity of antioxidant
      enzymes compared in the groups control 4 to test 2 (in groups which do not given
      coordination compound Cu (II): CAT (control 4 - 13.38+/-7.60 BU/gHb; test 2 -
      10.12+/-3.62 BU/gHb) SOD (control 4 - 1138.88+/-490.10 U/gHb/100ml; test 2 -
      1283.85+/-439.87 U/gHb/100ml) and GPX (control 4 - 65.18+/-20.94 U/gHb; test 2 -
      90.27+/-19.42 U/gHb). CONCLUSIONS: The study shows that the complex deacon-tetra
      (N1,3-triazole,kN2) copper (II) affects the activity of antioxidant enzymes CAT,
      SOD and GPX.

PMID- 24021825
TI  - [Malignant and non-malignant cartilaginous tumours of the larynx].
AB  - INTRODUCTION: Cartilaginous tumours of the larynx are rare. They usually involve
      cricoid cartilage, less frequently thyroid cartilage and other cartilages. The
      most significant clinical manifestations are hoarseness, dyspnea, dysphagia or a
      neck mass. On physical examination, tumour is found as a bulge with intact mucosa
      or a tumour situated in a part of the larynx also with fixation. CT scanning is
      the mainstay of radiographic imaging. The histopathologic diagnosis is made after
      the surgical excision. Prognosis for survival is good. The recurrences occur very
      often, also with malignant transformation and require laryngectomy. MATERIAL: We
      presented 11 patients (including symptoms, involved cartilage, laryngoscopy
      examination, histopathologic diagnosis, treatment and the follow-up). RESULTS: 6
      patients manifested hoarseness, 5 dyspnea, 3 dysphagia, 1 neck mass as the first
      symptom. In laryngoscopy a tumour with intact mucosa was situated in subglottis -
      5 patients, in supraglottis - 2 patients and in half of the larynx with fixation 
      4 patients. The majority of tumours involved the cricoid cartilage - in 9 cases,
      the rest arytenoid and epiglottic cartilage. The histopathology diagnosis were
      given after surgery, only in one case after biopsy. There were 7 patients with
      chondrosarcoma and four with chondroma. We did not observe lymph node or distant
      metastases. All patients were treated surgically. Follow-up of patients with
      chondrosarcoma were 5 to 17 years without recurrence. However, two recurrences of
      chondroma appeared to be chondrosarcomas and required laryngectomy.

PMID- 24021826
TI  - [Kinesitherapy in patients with the peripheral vestibular system disorders].
AB  - INTRODUCTION: Kinesitherapy is widely accepted management in patients with
      vertigo and imbalance, but there has been inadequate evidence that one form of
      therapy is superior to another. THE AIM: of the study was to compare
      effectiveness of two kinesitherapy protocols in patients with the peripheral
      vestibular system disorders. MATERIAL AND METHODS: Fifty patients (mean age
      46.0+/-13.1 year) with vertigo and balance instability lasting over 3 months with
      unilateral vestibular disorder, confirmed in Videnystagmography, were included in
      the study. Thirty patients underwent supervised and 20 patients home-based
      exercise programs. All of them were assessed three times at the baseline, after 4
      weeks and 3 months, on vertigo intensity and frequency with the Vertigo Syndrome
      Scale (VSS), Vertigo Visual Analog Scale (VAS) and clinical unsteadiness with
      tests (Romberg, Amended Motor Club Assesment (AMCA), Eurofit test - standing on
      one leg. RESULTS: In both groups the clinical tasks and the intensity of vertigo
      in VAS significantly decreased. The mean value of VSS (part physical and
      emotional)score significantly decreased only in supervised group at the end of 4
      weeks and 3 months (p=ns). Recovery was more dynamic in supervised group than
      home-based exercises group, in AMCA test (3.9 vs. 1.3 s, p<0.05) in Eurofit tests
      eye open (14.1 vs. 0.9 s, p<0.05) and eye closed (3.5 vs. 1 s, p<0.05).
      CONCLUSIONS: In patients with unilateral peripheral vestibular dysfunction
      supervised and home-based group kinesitherapy is an effective treatment method.
      In supervised group patients recovery has been faster.

PMID- 24021827
TI  - [The expression assessment of the estrogen, progesterone and HER2 receptors in
      selected malignant tumors of the salivary glands].
AB  - INTRODUCTION: The incidence of the malignant tumors of the salivary glands is
      relatelively low. However, rapid locoregional progression, distant metastases
      occurrence and high local recurrence rate occurring despite radical surgical
      treatment, significantly affect the outcome. Malignant tumors of the salivary
      glands are characterized by low radiosensitivity and poor response to systemic
      therapy. Therefore there is a need for new targeted therapies which may improve
      the prognosis. In some aspects, malignant tumors of the salivary glands are
      similar to breast cancers. Efficacy of hormonal replacement therapy and the
      treatment with the monoclonal antibody (trastuzumab) in the treatment of breast
      cancer is well known and confirmed. Criterion determining the qualification for
      treatment is the presence of hormone receptors and HER2 receptors in the tumor.
      AIM: The aim of this study was to evaluate the expression of estrogen receptor,
      progesterone receptor and HER2 in selected salivary gland malignancies. MATERIALS
      AND METHODS: Study group consisted of 51 patients with the salivary glands
      cancer. In the study group there were 42 tumors in the parotid gland, 7 tumors of
      the submandibular gland, 1 in the mucosa of the cheek and 1 tumor in the tongue.
      Histologically material comprised of muco-epidermoid carcinoma (10), adenoid
      cystic carcinoma (8), salivary duct (7), adenocarcinoma (6), squamous cell
      carcinoma (6), mioepithelial carcinoma (5) and other (9). In all cases
      immunohistochemical analysis of the estrogen receptor, progesterone receptor and
      HER2 receptor was performed. RESULTS: The expression of the estrogen receptor was
      found in 18% of tumors (9 patients). The expression of the progesterone receptor
      was found in 20% (10 patients). HER2 expression was found in 10% of tumors and
      was related to only one histological type of tumor - salivary duct carcinoma.
      CONCLUSION: HER2 expression in malignant tumors of the salivary glands,
      especially in salivary duct carcinoma may be of use in future implementation of
      new targeted therapies based on monoclonal antibodies.

PMID- 24021828
TI  - Value of high resolution ultrasonography in assessment of laryngeal lesions.
AB  - OBJECTIVE: The aim of this study is to evaluate the value of high resolution
      ultrasonography (HRUS) in diagnosis of various laryngeal lesions which already
      diagnosed with rigid endoscopy. STUDY DESIGN: Prospective study with control
      group. PATIENTS AND METHODS: Sixty-six patients were suffering from throat
      symptoms and pre-examined by rigid endoscopy under local anesthesia and diagnosed
      to have a laryngeal lesion and 32 volunteers compose the control group. All 98
      persons (patients and control groups) were examined by HRUS. RESULTS: HRUS was
      helpful in describing various laryngeal lesions, vocal fold polyps (17) 25.7%,
      glottic cancer (6) 9.1%, epiglottic enlargement (2) 3.1% and one patient had
      laryngocele (1.5%). HRUS was highly significant in diagnosis of subglottic
      lesions (10) 15.2%. Also vocal fold mobility can be demonstrated by HRUS. While
      interarytenoid lesions (17) 25.8% and small laryngeal lesions as vocal fold
      nodules (13) 19.6% were difficult to be described. CONCLUSION: Rigid endoscopy in
      laryngeal examination gives us large, bright image but it is difficult to
      diagnose patients with a sensitive gag reflex, patients with neck or jaw diseases
      or stridor and very difficult in infants and children. HRUS is an alternative
      method in diagnosis of some laryngeal lesions, and it is superior in the
      diagnosis of small subglottic lesions.

PMID- 24021829
TI  - ENT manifestations of Wegeners granulomatosis.
AB  - Wegeners granulomatosis is a necrotizing granulomatous vasculitis with
      multisystemic involvement. We present two cases of Wegener's presenting with
      otological manifestations as the first symptom. These symptoms are subtle and
      diagnosis may be easily overlooked. Hence a high index of suspicion is required.
      Early diagnosis and treatment goes a long way in improving the outcomes and in
      preventing further complications. 

PMID- 24021830
TI  - [Ethmoid sinus mucocele penetrating to the orbit and anterior cranial fossa -
      case report].
AB  - Paranasal sinus mucocele is the cystic formation lined by inflammatory changed
      mucoperiosteum. This is slow-growing pathology with a tendency to bone erosion.
      The symptoms are dependent on the direction of the penetration, and are as
      follows: increasing headaches, deformations of frontal or orbital region,
      ophthalmic manifestations such as lacrimation, decreased visual acuity,
      exophthalmos, ocular movement limitation, diplopia. The most common location of
      the mucocele is fronto-ethmoid region. The most useful diagnostic tests are a
      magnetic resonance imaging (MRI) and a computed tomography (CT) which show the
      progress of the disease and bone destructions. Surgery is the only method of
      treatment (external approach or FESS). This paper reports the case of a 74-year
      old woman with ethmoid mucocele penetrating into the orbit, frontal sinus and
      anterior cranial fossa with compression of frontal lobe of the brain. The patient
      underwent CT and MRI and was treated with endoscopic intranasal marsupialization
      of the cyst. There are no clinical signs of disease recurrence 7 months after
      surgery. The endoscopic surgical management in treatment of sinus mucocele is a
      good alternative to the operation from external approach because of its low
      invasiveness, low complication risk, rapid healing and good therapeutic effects. 

PMID- 24021831
TI  - A fluoro versus a nitro derivative-a high-performance liquid chromatography study
      of two basic analytes with different reversed phases and silica phases as basis
      for the separation of a positron emission tomography radiotracer.
AB  - To develop a basis for the separation of a (18)F-labeled PET radiotracer from its
      nitro precursor, we performed an analytical HPLC study using the unlabeled
      reference compound and the corresponding nitro precursor. Aim of the study was to
      find a separation in which the fluoro derivative elutes in front of the nitro
      precursor with appropriate separation parameters. Several RP phases as well as a
      bare silica column were investigated with ACN and MeOH as organic modifiers and
      aqueous NH4OAc because of the basic character of the analytes. Four types of
      separation were observed based on different interaction mechanisms. When ACN/20mM
      NH4OAc aq. was used mainly cationic-exchange and hydrophobic interactions
      contributed to the retention. A reversal of elution order could be observed
      starting from 95% ACN and subsequent increasing of the water content. This
      phenomenon was observed for all RP phases and seems to be independent of the
      different spacers bound to the silica. By contrast, using MeOH/20mM NH4OAc aq.
      the elution order depends on the phase material. Two columns with the potential
      to perform pi-pi interactions showed different separation behavior compared to
      the other RP phases. 

PMID- 24021832
TI  - Sequential cloud-point extraction for toxicological screening analysis of
      medicaments in human plasma by high pressure liquid chromatography with diode
      array detector.
AB  - A complex extraction system with the use of cloud-point extraction technique
      (CPE) was developed for sequential isolation of basic and acidic/neutral
      medicaments from human plasma/serum, screened by HPLC/DAD method. Eight model
      drugs (paracetamol, promazine, chlorpromazine, amitriptyline, salicyclic acid,
      opipramol, alprazolam and carbamazepine) were chosen for the study of optimal CPE
      conditions. The CPE technique consists in partition of an aqueous sample with
      addition of a surfactant into two phases: micelle-rich phase with the isolated
      compounds and water phase containing a surfactant below the critical micellar
      concentration, mainly under influence of temperature change. The proposed
      extraction system consists of two chief steps: isolation of basic compounds (from
      pH 12) and then isolation of acidic/neutral compounds (from pH 6) using
      surfactant Triton X-114 as the extraction medium. Extraction recovery varied from
      25.2 to 107.9% with intra-day and inter-day precision (RSD %) ranged 0.88-1087
      and 5.32-17.96, respectively. The limits of detection for the studied medicaments
      at lambda 254nm corresponded to therapeutic or low toxic plasma concentration
      levels. Usefulness of the proposed CPE-HPLC/DAD method for toxicological drug
      screening was tested via its application to analysis of two serum samples taken
      from patients suspected of drug overdosing. 

PMID- 24021833
TI  - Air-assisted liquid-liquid microextraction used for the rapid determination of
      organophosphorus pesticides in juice samples.
AB  - A novel and simple air-assisted liquid-liquid microextraction (AALLME) is
      introduced to analyze the organophosphorus pesticide (OPP) residues in fruit
      juice samples, using the gas chromatography-flame photometric detection (GC-FPD).
      In this method, fine extraction solvent drops are rapidly formed and dispersed
      into the aqueous samples, by using a syringe to withdraw and push-out the mixture
      of aqueous sample solution and extraction solvent several times. The parameters
      affecting the extraction efficiency were investigated including the type and
      volume of the extraction solvent, salt addition, extraction times, and pH. Under
      optimized conditions, the method showed good linearities with the correlation
      coefficients (gamma) higher than 0.9988, and the sensitivity with the limits of
      detection (LODs) between 0.02MUgL(-1) and 0.6MUgL(-1). The method was applied to
      determine the OPP residues in juice samples and the recoveries were ranged from
      79% to 113% with relative standard deviations (RSDs) of 0.4-9.9%. The feasibility
      of the method in real samples was proved. 

PMID- 24021834
TI  - Reversible entrapment of plasmid deoxyribonucleic acid on different
      chromatographic supports.
AB  - HPLC based analytical assay is a powerful technique that can be used to
      efficiently monitor plasmid DNA (pDNA) purity and quantity throughout the entire
      purification process. Anion exchange monolithic and non-porous particle based
      stationary phases were used to study the recovery of the different pDNA isoforms
      from the analytical column. Three differently sized pDNA molecules of 3.0kbp,
      5.2kbp and 14.0kbp were used. Plasmid DNA was injected onto columns under the
      binding conditions and the separation of the isoforms took place by increasing
      the ionic strength of the elution buffer. While there was no substantial decrease
      of the recovered supercoiled and linear isoforms of the pDNA with the increase of
      the plasmid size and with the increase of the flow rate (recoveries in all cases
      larger than 75%), a pronounced decrease of the oc isoform recovery was observed.
      The entrapment of the oc pDNA isoform occurred under non-binding conditions as
      well. The partial oc isoform elution from the column could be achieved by
      decreasing the flow rate of the elution mobile phase. The results suggested a
      reversible entrapment of the oc isoform in the restrictions within the pores of
      the monolithic material as well as within the intra-particle space of the non
      porous particles. This phenomenon was observed on both types of the stationary
      phase morphologies and could only be connected to the size of a void space
      through which the pDNA needs to migrate. A prediction of reversible pDNA
      entrapment was successfully estimated with the calculation of Peclet numbers, Pe,
      which defines the ratio between a convective and diffusive mass transport. 

PMID- 24021835
TI  - Quantitative analysis of intracellular coenzymes in Saccharomyces cerevisiae
      using ion pair reversed phase ultra high performance liquid chromatography tandem
      mass spectrometry.
AB  - A fast, sensitive and specific analytical method, based on ion pair reversed
      phase ultrahigh performance liquid chromatography tandem mass spectrometry, IP-RP
      UHPLC-MS/MS, was developed for quantitative determination of intracellular
      coenzyme A (CoA), acetyl CoA, succinyl CoA, phenylacetyl CoA, flavin
      mononucleotide, (FMN), flavin adenine dinucleotide, (FAD), NAD, NADH, NADP,
      NADPH. Dibutylammonium acetate (DBAA) was used as volatile ion pair reagent in
      the mobile phase. Addition of DBAA to the sample solutions resulted in an
      enhanced sensitivity for the phosphorylated coenzymes. Tris (2-carboxyethyl)
      phosphine hydrochloride (TCEP.HCl), was added to keep CoA in the reduced form.
      Isotope dilution mass spectrometry (IDMS) was applied for quantitative
      measurements for which culture derived global U-(13)C-labeled cell extract was
      used as internal standard. The analytical method was validated by determining the
      limit of detection, the limit of quantification, repeatability and intermediate
      precision. The method was successfully applied for quantification of coenzymes in
      the cell extracts of Saccharomyces cerevisiae. 

PMID- 24021837
TI  - Alternative thresholding methods for fMRI data optimized for surgical planning.
AB  - Current methods for thresholding functional magnetic resonance imaging (fMRI)
      maps are based on the well-known hypothesis-test framework, optimal for
      addressing novel theoretical claims. However, these methods as typically
      practiced have a strong bias toward protecting the null hypothesis, and thus may
      not provide an optimal balance between specificity and sensitivity in forming
      activation maps for surgical planning. Maps based on hypothesis-test thresholds
      are also highly sensitive to sample size and signal-to-noise ratio, whereas many
      clinical applications require methods that are robust to these effects. We
      propose a new thresholding method, optimized for surgical planning, based on
      normalized amplitude thresholding. We show that this method produces activation
      maps that are more reproducible and more predictive of postoperative cognitive
      outcome than maps produced with current standard thresholding methods. 

PMID- 24021836
TI  - The influence of spatial resolution and smoothing on the detectability of resting
      state and task fMRI.
AB  - Functional MRI blood oxygen level-dependent (BOLD) signal changes can be subtle,
      motivating the use of imaging parameters and processing strategies that maximize
      the temporal signal-to-noise ratio (tSNR) and thus the detection power of
      neuronal activity-induced fluctuations. Previous studies have shown that
      acquiring data at higher spatial resolutions results in greater percent BOLD
      signal changes, and furthermore that spatially smoothing higher resolution fMRI
      data improves tSNR beyond that of data originally acquired at a lower resolution.
      However, higher resolution images come at the cost of increased acquisition time,
      and the number of image volumes also influences detectability. The goal of our
      study is to determine how the detection power of neuronally induced BOLD
      fluctuations acquired at higher spatial resolutions and then spatially smoothed
      compares to data acquired at the lower resolutions with the same imaging
      duration. The number of time points acquired during a given amount of imaging
      time is a practical consideration given the limited ability of certain
      populations to lie still in the MRI scanner. We compare acquisitions at three
      different in-plane spatial resolutions (3.50*3.50mm(2), 2.33*2.33mm(2),
      1.75*1.75mm(2)) in terms of their tSNR, contrast-to-noise ratio, and the power to
      detect both task-related activation and resting-state functional connectivity.
      The impact of SENSE acceleration, which speeds up acquisition time increasing the
      number of images collected, is also evaluated. Our results show that after
      spatially smoothing the data to the same intrinsic resolution, lower resolution
      acquisitions have a slightly higher detection power of task-activation in some,
      but not all, brain areas. There were no significant differences in functional
      connectivity as a function of resolution after smoothing. Similarly, the reduced
      tSNR of fMRI data acquired with a SENSE factor of 2 is offset by the greater
      number of images acquired, resulting in few significant differences in detection
      power of either functional activation or connectivity after spatial smoothing. 

PMID- 24021839
TI  - Therapeutic apheresis in pediatric patients with acute CNS inflammatory
      demyelinating disease.
AB  - BACKGROUND/AIMS: In adults, plasma exchange (PE) has been shown to be an
      efficient treatment for severe relapses of acute inflammatory CNS demyelinating
      diseases. The aim of this study was to evaluate the safety and efficacy of this
      treatment in pediatric patients. METHODS: We retrospectively analyzed a single
      center cohort of pediatric patients with inflammatory CNS demyelinating disorders
      who underwent apheresis between 2007 and 2011. RESULTS: Ten patients (mean age:
      11.6 +/- 3.4 years) with an acute relapse of multiple sclerosis (n = 5),
      neuromyelitis optica (n = 2) or acute disseminated encephalomyelitis were
      included. All received methylprednisolone prior to treatment with either PE (n =
      5) or immunoadsorption (n = 5). Apheresis-related side effects were either self
      limiting or easily managed. EDSS (Expanded Disability Status Scale) improved in 7
      of 8 patients during apheresis and in all patients within 30 days from a median
      of 7.5 to 1 (p < 0.01). The visual acuity initially worsened during the procedure
      in 3 of 7 affected eyes (mean 0.09), but improved in all at follow-up (mean: 0.5;
      p = 0.008). CONCLUSIONS: Apheresis was well tolerated and associated with a
      favorable outcome in all pediatric patients similar to reports in adults.

PMID- 24021840
TI  - Understanding the art of feminist pedagogy: facilitating interpersonal skills
      learning for nurses.
AB  - The purpose of this study is to explore feminist pedagogy integrated with
      facilitation skills. A pedagogy project was undertaken with students
      participating in the BSc (Hons) Nursing programme, whereby a module,
      "Interpersonal Skills for Nurses" was developed for 72 year 1 students. A
      feminist pedagogy involves employing the powers of diversity to create an
      environment where all students' voices are heard. It values the power of sharing
      to create a community of learners in which teachers and students share their
      talents, skills and abilities to enhance the learning of all (Chinn, 2001). An
      end of semester evaluation provided feedback which indicated this was a valuable
      module to teach year 1 student nurses. It highlighted that student nurses found
      the topic both interesting and relevant and felt it was taught in a way that
      promoted their personal development and identity as a nurse.

PMID- 24021838
TI  - The mid-fusiform sulcus: a landmark identifying both cytoarchitectonic and
      functional divisions of human ventral temporal cortex.
AB  - Human ventral temporal cortex (VTC) plays a pivotal role in high-level vision. An
      under-studied macroanatomical feature of VTC is the mid-fusiform sulcus (MFS), a
      shallow longitudinal sulcus separating the lateral and medial fusiform gyrus
      (FG). Here, we quantified the morphological features of the MFS in 69 subjects
      (ages 7-40), and investigated its relationship to both cytoarchitectonic and
      functional divisions of VTC with four main findings. First, despite being a minor
      sulcus, we found that the MFS is a stable macroanatomical structure present in
      all 138 hemispheres with morphological characteristics developed by age 7.
      Second, the MFS is the locus of a lateral-medial cytoarchitectonic transition
      within the posterior FG serving as the boundary between cytoarchitectonic regions
      FG1 and FG2. Third, the MFS predicts a lateral-medial functional transition in
      eccentricity bias representations in children, adolescents, and adults. Fourth,
      the anterior tip of the MFS predicts the location of a face-selective region,
      mFus-faces/FFA-2. These findings are the first to illustrate that a
      macroanatomical landmark identifies both cytoarchitectonic and functional
      divisions of high-level sensory cortex in humans and have important implications
      for understanding functional and structural organization in the human brain. 

PMID- 24021841
TI  - The working lives of nurse teachers in mainland China and the United Kingdom: a
      questionnaire survey.
AB  - BACKGROUND: Nurse education has undergone considerable changes creating new
      opportunities and challenges for nurse teachers. Limited comparative research of
      the working lives of nurse teachers has been reported, thus similarities and
      differences that may exist are unidentified. AIM: This paper reports a study of
      the working lives of nurse teachers in mainland China and the United Kingdom.
      DESIGN: A cross-sectional questionnaire survey. PARTICIPANTS: Census sample of
      nurse teachers working in four nursing schools in mainland China (n=3) and the
      United Kingdom (n=1). The overall response rate was 56.8% (China=61, 61.0%,
      UK=60, 53.1%). METHODS: Completion of questionnaire specifically developed for
      the study but comprising six validated tools to collecting data on: job
      satisfaction, sense of coherence, role conflict and role ambiguity, work
      empowerment and professional identification. Data on self-reported roles and
      personal details were also collected. Data were collected between September 2008
      and January 2009. RESULTS: Both samples were satisfied with their jobs overall
      but reported low levels of satisfaction with promotion. Chinese nurse teachers
      working full-time reported the lowest level for sense of coherence and
      professional identification. Nurse teachers working full-time in the United
      Kingdom reported the highest role conflict score. Sense of coherence and work
      empowerment were significantly and positively correlated to job satisfaction.
      Role conflict and role ambiguity were negatively correlated (but not always
      significantly) to job satisfaction and its facets. For respondents in mainland
      China, professional identification was significantly and positively correlated
      with overall job satisfaction and its facets. CONCLUSIONS: Strategies to improve
      job satisfaction with promotion opportunities for both samples are indicated.
      Respondents working full-time in both mainland China and the United Kingdom
      experienced greater challenges at work than their part-time colleagues.

PMID- 24021842
TI  - A new locus for familial temporal lobe epilepsy on chromosome 3q.
AB  - BACKGROUND: Temporal lobe epilepsy (TLE) is a common and heterogeneous focal
      epilepsy syndrome with a complex etiology, involving both environmental and
      genetic factors. Several familial forms of TLE have been described, including
      familial lateral TLE (FLTLE), familial mesial TLE (FMTLE) without hippocampal
      sclerosis, and FMTLE with hippocampal sclerosis. Mutations have been identified
      only in the leucine-rich, glioma-inactivated 1 (LGI1) gene on chromosome 10q22
      q24 in FLTLE. Several loci have been mapped in families with FMTLE, but
      responsible genes have not been found. We report clinical evaluation in a large
      family with FMTLE and a new genetic locus. METHODS: We conducted a genome-wide
      scan using 10cM-spaced microsatellite markers on a family with TLE. Seven
      individuals had TLE without antecedent FS; four other individuals had FS during
      childhood, but no subsequent epilepsy. Patients with TLE had infrequent simple
      partial, complex partial and secondarily generalized seizures that generally
      responded well to treatment. The proband had no hippocampal sclerosis. The mode
      of inheritance appeared to be autosomal dominant with incomplete penetrance.
      Linkage analysis was performed using the Genehunter software. Regions with LOD
      score>1 and those that were poorly informative in the first-pass scan were
      further genotyped. RESULTS: Linkage was identified on chromosome 3q25-q26 in a
      13cM region flanked by markers D3S1584 and D3S3520, with a peak LOD score of
      3.23. This interval does not correspond to any previously known locus for
      familial epilepsy or FS. KCNAB1, encoding a voltage-gated, shaker-related
      potassium channel, and NLGN1, encoding a member of a family of neuronal cell
      surface protein were excluded as disease causing mutations. CONCLUSION: We
      identified a novel locus for familial TLE with FS, providing additional evidence
      of the complexity and genetic heterogeneity of familial focal epilepsy.

PMID- 24021843
TI  - 'Suspicious for a follicular neoplasm' before and after the Bethesda System for
      Reporting Thyroid Cytopathology: impact of standardized terminology.
AB  - BACKGROUND: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC)
      standardized the terminology for indeterminate diagnoses, but the performance of
      the indeterminate categories before and after TBSRTC has not been compared. This
      study evaluates the 'suspicious for a follicular or Hurthle cell neoplasm'
      (SFN/HCN) category before and after the introduction of TBSRTC at a single
      institution and in a meta-analysis of the literature. METHODS: A meta-analysis
      compiled findings from publications on SFN/HCN or similar diagnoses before and
      after the introduction of TBSRTC. The pathology database at our institution
      identified all SFN/HCN or similar diagnoses in the 8 years surrounding the
      introduction of TBSRTC, and those cases were correlated with the surgical follow
      up. RESULTS: In the meta-analysis, the fraction of cases called SFN/HCN or the
      equivalent increased from 6.1 to 7.4% (p = 0.0002); the surgical follow-up rate
      increased from 55 to 61% (p < 0.00001), and the histological malignancy rate
      among the cases that were resected increased from 22 to 28% (p = 0.03) after
      TBSRTC. In our institutional experience, the introduction of TBSRTC did not
      coincide with any significant changes. CONCLUSION: Standardized terminology
      clearly coincided with increases in follow-up and the malignancy rate of SFN/HCN.
      A change in the same statistics was not seen in our institutional experience.

PMID- 24021845
TI  - Music to the inner ears: exploring individual differences in musical imagery.
AB  - In two studies, we explored the frequency and phenomenology of musical imagery.
      Study 1 used retrospective reports of musical imagery to assess the contribution
      of individual differences to imagery characteristics. Study 2 used an experience
      sampling design to assess the phenomenology of musical imagery over the course of
      one week in a sample of musicians and non-musicians. Both studies found episodes
      of musical imagery to be common and positive: people rarely wanted such
      experiences to end and often heard music that was personally meaningful. Several
      variables predicted musical imagery, including personality, musical preferences,
      and positive mood. Musicians tended to hear musical imagery more often, but they
      reported less frequent episodes of deliberately-generated imagery. Taken
      together, the present research provides new insights into individual differences
      in musical imagery, and it supports the emerging view that such experiences are
      common, positive, and more voluntary than previously recognized. 

PMID- 24021844
TI  - Cognitive reserve protects against apathy in individuals with human
      immunodeficiency virus.
AB  - Apathy is associated with impaired neuropsychological functioning in individuals
      with HIV. While cognitive reserve (CR) delays neurocognitive decline, CR's
      relationship with apathy has never been studied. We examined CR's association
      with apathy in 116 HIV-positive individuals recruited from an urban AIDS center
      and assessed whether this relationship is moderated by age and/or disease
      severity. Participants completed the Wechsler Test of Adult Reading and Apathy
      Evaluation Scale. A CR-composite, combining years of education and word-reading
      ability, significantly predicted apathy (t = -2.37, p = .02). CR's relationship
      with apathy was not moderated by age, but participants with nadir CD4 levels <=
      200 demonstrated a stronger association (t = -3.25, p = .002) than those with
      nadir CD4 levels > 200 (t = -0.61, p = .55). These findings suggest a protective
      effect of CR against apathy in HIV-infected individuals across the age span,
      particularly after a certain threshold of disease severity.

PMID- 24021846
TI  - Nightmare frequency is related to a propensity for mirror behaviors.
AB  - We previously reported that college students who indicated engaging in frequent
      dream-enacting behaviors also scored high on a new measure of mirror behaviors,
      which is the propensity to imitate another person's emotions or actions. Since
      dream-enacting behaviors are frequently the culmination of nightmares, one
      explanation for the observed relationship is that individuals who frequently
      display mirror behaviors are also prone to nightmares. We used the Mirror
      Behavior Questionnaire (MBQ) and self-reported frequencies of nightmares to
      assess this possibility. A sample of 480 students, consisting of 188 males
      (19.2+/-1.73 years) and 292 females (19.0+/-1.55 years) enrolled in a first-year
      university psychology course, participated for course credit. They completed a
      battery of questionnaires that included the 16-item MBQ, plus an item about
      nightmare frequency (NMF) in the past 30 days. NMF scores were split to create
      low, medium, and high NMF groups. MBQ total scores were significantly higher for
      female than for male subjects, but an interaction revealed that this was true
      only for Hi-NMF subjects. MBQ Factor 4, Motor Skill Imitation, paralleled this
      global interaction for females, whereas MBQ Factor 3, Sleepiness/Anger Contagion,
      was elevated only for Hi-NMF males. Item analyses indicated that Hi- and Med-NMF
      females scored higher than Lo-NMF females on the 3 items of Factor 4 that reflect
      voluntary imitation (imitating famous/cartoon voices, being a physically active
      spectator, and learning new skills by observing), as well as on 2 other items
      that reflect involuntary imitation (contagious yawning and self-rated empathy).
      Although Hi- and Lo-NMF males differed most clearly on the sleepiness item of
      Factor 3, all 3 items on this factor (including anger contagion and contagious
      yawning) are plausibly associated with perception of and response to social
      threat. Results provide evidence that among females nightmares are associated
      with voluntary and involuntary mirror behaviors during wakefulness, while among
      males nightmares are associated with threat-related mirror behaviors during
      wakefulness. They thus support the possibility that the association between
      mirror behaviors and dream-enacting behaviors is due to a common mirror neuron
      mechanism that underlies mirror behaviors and nightmares and that involves motor,
      rather than emotional, resonance. These results have implications for
      understanding the comorbidity of nightmares and other pathological symptoms such
      as imitative suicidal behaviors, the influence of observational learning on
      dissociative symptomatology, and the predominance of threat and aggression in the
      dream enacting behaviors of REM sleep behavior disorder.

PMID- 24021847
TI  - Experimentally-induced dissociation impairs visual memory.
AB  - Dissociation is a phenomenon common in a number of psychological disorders and
      has been frequently suggested to impair memory for traumatic events. In this
      study we explored the effects of dissociation on visual memory. A dissociative
      state was induced experimentally using a mirror-gazing task and its short-term
      effects on memory performance were investigated. Sixty healthy individuals took
      part in the experiment. Induced dissociation impaired visual memory performance
      relative to a control condition; however, the degree of dissociation was not
      associated with lower memory scores in the experimental group. The results have
      theoretical and practical implications for individuals who experience frequent
      dissociative states such as patients with posttraumatic stress disorder (PTSD). 

PMID- 24021848
TI  - Lost in the crowd: entitative group membership reduces mind attribution.
AB  - This research examined how and why group membership diminishes the attribution of
      mind to individuals. We found that mind attribution was inversely related to the
      size of the group to which an individual belonged (Experiment 1). Mind
      attribution was affected by group membership rather than the total number of
      entities perceived at once (Experiment 2). Moreover, mind attribution to an
      individual varied with the perception that the individual was a group member.
      Participants attributed more mind to an individual that appeared distinct or
      distant from other group members than to an individual that was perceived to be
      similar or proximal to a cohesive group (Experiments 3 and 4). This effect
      occurred for both human and nonhuman targets, and was driven by the perception of
      the target as an entitative group member rather than by the knowledge that the
      target was an entitative group member (Experiment 5). 

PMID- 24021849
TI  - Masked and unmasked priming in schizophrenia.
AB  - Dehaene et al. (2003) showed an absence of conscious, but not masked, conflict
      effects when patients with schizophrenia performed a number-categorisation
      priming task. We aimed to replicate these influential results using a different
      word-categorisation priming task. Counter to Dehaene et al.'s findings, 21
      patients and 20 healthy controls showed similar congruence effects for both
      masked and visible primes. Within patients, a reduced congruence effect for
      visible primes associated with longer duration of illness and more severe
      behavioural disorganisation. Patients, unlike controls, were no slower to respond
      to targets that followed visible compared to masked primes. Conscious conflict
      effects on priming tasks are not universally reduced in schizophrenia but may
      associate with chronicity and behavioural disorganisation. That patients were no
      slower when the preceding primes were clearly visible accords with evidence
      elsewhere that information processing in schizophrenia is driven more by
      immediate conscious experience and constrained less by prior events. 

PMID- 24021850
TI  - Testing the involvement of the prefrontal cortex in lucid dreaming: a tDCS study.
AB  - Recent studies suggest that lucid dreaming (awareness of dreaming while dreaming)
      might be associated with increased brain activity over frontal regions during
      rapid eye movement (REM) sleep. By applying transcranial direct current
      stimulation (tDCS), we aimed to manipulate the activation of the dorsolateral
      prefrontal cortex (DLPFC) during REM sleep to increase dream lucidity. Nineteen
      participants spent three consecutive nights in a sleep laboratory. On the second
      and third nights they randomly received either 1 mA tDCS for 10 min or sham
      stimulation during each REM period starting with the second one. According to the
      participants' self-ratings, tDCS over the DLPFC during REM sleep increased
      lucidity in dreams. The effects, however, were not strong and found only in
      frequent lucid dreamers. While this indicates some preliminary support for the
      involvement of the DLPFC in lucid dreaming, further research, controlling for
      indirect effects of stimulation and including other brain regions, is needed.

PMID- 24021851
TI  - Resource depletion does not influence prospective memory in college students.
AB  - This paper reports an experiment designed to investigate the potential influence
      of prior acts of self-control on subsequent prospective memory performance.
      College undergraduates (n=146) performed either a cognitively depleting initial
      task (e.g., mostly incongruent Stroop task) or a less resource-consuming version
      of that task (e.g., all congruent Stroop task). Subsequently, participants
      completed a prospective memory task that required attentionally demanding
      monitoring processes. The results demonstrated that prior acts of self-control do
      not impair the ability to execute a future intention in college-aged adults. We
      conceptually replicated these results in three additional depletion and
      prospective memory experiments. This research extends a growing number of studies
      demonstrating the boundary conditions of the resource depletion effect in
      cognitive tasks. 

PMID- 24021852
TI  - More of myself: manipulating interoceptive awareness by heightened attention to
      bodily and narrative aspects of the self.
AB  - Psychology distinguishes between a bodily and a narrative self. Within
      neuroscience, models of the bodily self are based on exteroceptive sensorimotor
      processes or on the integration of interoceptive sensations. Recent research has
      revealed interactions between interoceptive and exteroceptive processing of self
      related information, for example that mirror self-observation can improve
      interoceptive awareness. Using heartbeat perception, we measured the effect on
      interoceptive awareness of two experimental manipulations, designed to heighten
      attention to bodily and narrative aspects of the self. Participants gazed at a
      photograph of their own face or at self-relevant words. In both experimental
      conditions interoceptive awareness was significantly increased, compared to
      baseline. Results show that attention to narrative aspects of self, previously
      regarded as relying on higher-order processes, has an effect similar to self-face
      stimuli in improving interoceptive awareness. Our findings extend the previously
      observed interaction between the bodily self and interoception to more abstract
      amodal representations of the self. 

PMID- 24021853
TI  - Hedonic value of intentional action provides reinforcement for voluntary
      generation but not voluntary inhibition of action.
AB  - Intentional inhibition refers to stopping oneself from performing an action at
      the last moment, a vital component of self-control. It has been suggested that
      intentional inhibition is associated with negative hedonic value, perhaps due to
      the frustration of cancelling an intended action. Here we investigate hedonic
      implications of the free choice to act or inhibit. Participants gave aesthetic
      ratings of arbitrary visual stimuli that immediately followed voluntary decisions
      to act or to inhibit action. We found that participants for whom decisions to act
      produced a strong positive hedonic value for the immediately following visual
      stimulus made more choices to act than those with weaker hedonic value for
      action. This finding is consistent with reinforcement learning of action
      decisions. However, participants who experienced inhibition as generating more
      positive hedonic value did not choose to inhibit more than other participants.
      Thus, voluntary inhibition of action did not act as reinforcement for future
      inhibitory behaviour. Our finding that inhibition of action lacks motivational
      capacity may explain why self-control is both difficult and limited. 

PMID- 24021854
TI  - A focused attention intervention for coping with ostracism.
AB  - Ostracism-being excluded and ignored-thwarts satisfaction of four fundamental
      needs: belonging, self-esteem, control, and meaningful existence. The current
      study investigated whether training participants to focus their attention on the
      here-and-now (i.e., focused attention) reduces distress from an ostracism
      experience. Participants were first trained in either focused or unfocused
      attention, and then played Cyberball, an online ball-tossing game for which half
      the participants were included or ostracized. Participants reported their levels
      of need satisfaction during the game, and after a short delay. Whereas both
      training groups experienced the same degree of need-threat in the immediate
      measure, participants who were trained in focused attention showed more recovery
      for the delayed measure. We reason that focused attention would not reduce the
      distress during the ostracism experience, but it aided in recovery by preventing
      participants from reliving the ostracism experience after it concludes. 

PMID- 24021856
TI  - Transmitting delusional beliefs in a hypnotic model of folie a deux.
AB  - Folie a deux is the transference of delusional ideas from one 'primary'
      individual to one or more 'secondary' individuals (Lasegue & Falret, 1877).
      However, it is difficult to investigate experimentally because often only one
      patient is identified as delusional. We investigated whether hypnosis could model
      the experiences of the secondary in this delusion. Our primary was a confederate,
      who displayed two delusional beliefs and attempted to transmit them to hypnotised
      subjects. We manipulated the status of the confederate so that they were
      portrayed as either "credible" or merely "interesting".Many high hypnotisable
      individuals adopted the confederate's beliefs and confabulated evidence in
      support of them.Also, subjects who interacted with a credible confederate
      extended their delusions beyond those displayed by the confederate. We discuss
      the strengths and limitations of this approach and suggest ways to improve the
      validity of this model. 

PMID- 24021855
TI  - Brain correlates of subjective freedom of choice.
AB  - The subjective feeling of free choice is an important feature of human
      experience. Experimental tasks have typically studied free choice by contrasting
      free and instructed selection of response alternatives. These tasks have been
      criticised, and it remains unclear how they relate to the subjective feeling of
      freely choosing. We replicated previous findings of the fMRI correlates of free
      choice, defined objectively. We introduced a novel task in which participants
      could experience and report a graded sense of free choice. BOLD responses for
      conditions subjectively experienced as free identified a postcentral area
      distinct from the areas typically considered to be involved in free action. Thus,
      the brain correlates of subjective feeling of free action were not directly
      related to any established brain correlates of objectively-defined free action.
      Our results call into question traditional assumptions about the relation between
      subjective experience of choosing and activity in the brain's so-called voluntary
      motor areas. 

PMID- 24021857
TI  - The self and involuntary memory: identifying with the victim increases memory
      accessibility for stressful events.
AB  - Autobiographical memory is intimately linked to the self. However, the relation
      between the self and involuntary recall has been understudied. Theoretically, the
      more relevant an event is to the self the more accessible the memory should be.
      In line with this prediction, the present study tested the hypothesis that self
      relevance of a stressor modulates involuntary recall. Healthy student
      participants viewed distressing film clips and were presented with information
      that defined the main characters as more or less similar to them, or without any
      information about the characters. In line with predictions, participants in the
      high self-relevance condition reported more involuntary memories of the film
      clips after one week compared to participants in the low self-relevance and
      control conditions. The findings support the theoretical relation between the
      self and memory accessibility and extend findings from previous research to the
      domain of involuntary recall. 

PMID- 24021858
TI  - SOD1-G93A mice exhibit muscle-fiber-type-specific decreases in glucose uptake in
      the absence of whole-body changes in metabolism.
AB  - BACKGROUND: Skeletal muscles play an important role in systemic glucose
      homeostasis and are purported to be the origin of the altered metabolic state
      observed in amyotrophic lateral sclerosis (ALS). OBJECTIVE: The purpose of this
      study was to evaluate whole-body and muscle-specific glucose metabolism in the
      SOD1-G93A mouse model of ALS. METHODS: We assessed glucose tolerance in early-,
      middle-, and late-stage SOD1-G93A and control mice using an intraperitoneal
      glucose tolerance test. We then measured the respiratory exchange ratio (CO2
      production/O2 consumption) as a function of fasting and feeding using indirect
      calorimetry in a subset of male mice at these time points. Finally, muscles from
      all mice were harvested to evaluate basal and insulin-stimulated glucose
      transport in fast- and slow-twitch muscles. RESULTS: No changes in systemic
      glucose clearance were observed in SOD1-G93A mice at any stage, nor were there
      changes in fasting insulin levels. Indirect calorimetry revealed an increase in
      the respiratory exchange ratio during the fed state at middle, but not at early
      or late stages of disease. Middle-stage SOD1-G93A mice exhibited decreased
      insulin-stimulated glucose uptake in fast-twitch, but not slow-twitch, skeletal
      muscle. Late-stage SOD1-G93A mice exhibited decreased insulin-stimulated glucose
      uptake in both fast- and slow-twitch muscle, as well as increased basal (non
      insulin-stimulated) glucose uptake. CONCLUSIONS: These results suggest that
      alterations in muscle metabolism occur in a fiber-type-specific manner in ALS,
      but do not necessarily lead to whole-body metabolic changes in SOD1-G93A mice.

PMID- 24021859
TI  - Contested space in the pharmacy: public attitudes to pharmacy harm reduction
      services in the West of Scotland.
AB  - BACKGROUND: Internationally, community pharmacies have become increasingly
      involved in providing harm reduction services and health advice to people who use
      illicit drugs. OBJECTIVE: This paper considers public opinion of community
      pharmacy services. It discusses attitudes to harm reduction services in the
      context of stigmatization of addiction and people who use drugs. METHODS: This
      exploratory study involved twenty-six purposively sampled members of the public,
      from the West of Scotland, participating in one of 5 focus groups. The groups
      were composed to represent known groups of users and non-users of community
      pharmacy, none of whom were problem drug users. RESULTS: Three thematic
      categories were identified: methadone service users in community pharmacies;
      attitudes to harm reduction policies; contested space. Harm reduction service
      expansion has resulted in a high volume of drug users in and around some Scottish
      pharmacies. Even if harm reduction services are provided discretely users'
      behavior can differentiate them from other pharmacy users. Drug users' behavior
      in this setting is commonly perceived to be unacceptable and can deter other
      consumers from using pharmacy services. The results of this study infer that
      negative public opinion is highly suggestive of stereotyping and stigmatization
      of people who use drugs. Participants considered that (1) community pharmacies
      were unsuitable environments for harm reduction service provision, as they are
      used by older people and those with children; (2) current drug policy is
      perceived as ineffective, as abstinence is seldom achieved and methadone was
      reported to be re-sold; (3) people who use drugs were avoided where possible in
      community pharmacies. CONCLUSIONS: Community pharmacy harm reduction services
      increasingly bring together the public and drug users. Study participants were
      reluctant to share pharmacy facilities with drug users. This paper concludes by
      suggesting mechanisms to minimize stigmatization.

PMID- 24021860
TI  - 'Hyperalgesia and functional sensory loss in restless legs syndrome' by Stiasny
      Kolster et al.

PMID- 24021862
TI  - Pain matrices and neuropathic pain matrices: a review.
AB  - The pain matrix is conceptualised here as a fluid system composed of several
      interacting networks. A nociceptive matrix receiving spinothalamic projections
      (mainly posterior operculoinsular areas) ensures the bodily specificity of pain
      and is the only one whose destruction entails selective pain deficits. Transition
      from cortical nociception to conscious pain relies on a second-order network,
      including posterior parietal, prefrontal and anterior insular areas. Second-order
      regions are not nociceptive-specific; focal stimulation does not evoke pain, and
      focal destruction does not produce analgesia, but their joint activation is
      necessary for conscious perception, attentional modulation and control of
      vegetative reactions. The ensuing pain experience can still be modified as a
      function of beliefs, emotions and expectations through activity of third-order
      areas, including the orbitofrontal and perigenual/limbic networks. The pain we
      remember results from continuous interaction of these subsystems, and substantial
      changes in the pain experience can be achieved by acting on each of them.
      Neuropathic pain (NP) is associated with changes in each of these levels of
      integration. The most robust abnormality in NP is a functional depression of
      thalamic activity, reversible with therapeutic manoeuvres and associated with
      rhythmic neural bursting. Neuropathic allodynia has been associated with
      enhancement of ipsilateral over contralateral insular activation and lack of
      reactivity in orbitofrontal/perigenual areas. Although lack of response of
      perigenual cortices may be an epiphenomenon of chronic pain, the enhancement of
      ipsilateral activity may reflect disinhibition of ipsilateral spinothalamic
      pathways due to depression of their contralateral counterpart. This in turn may
      bias perceptual networks and contribute to the subjective painful experience. 

PMID- 24021861
TI  - Pain in hospitalized children: Effect of a multidimensional knowledge translation
      strategy on pain process and clinical outcomes.
AB  - Hospitalized children frequently receive inadequate pain assessment and
      management despite substantial evidence to support effective pediatric pain
      practices. The objective of this study was to determine the effect of a
      multidimensional knowledge translation intervention, Evidence-based Practice for
      Improving Quality (EPIQ), on procedural pain practices and clinical outcomes for
      children hospitalized in medical, surgical and critical care units. A prospective
      cohort study compared 16 interventions using EPIQ and 16 standard care (SC) units
      in 8 Canadian pediatric hospitals. Chart reviews at baseline (time 1) and
      intervention completion (time 2) determined the nature and frequency of painful
      procedures and of pain assessment and pain management practices. Trained pain
      experts evaluated pain intensity 6 months post-intervention (time 3) during
      routine, scheduled painful procedures. Generalized estimating equation models
      compared changes in outcomes between EPIQ and SC units over time. EPIQ units used
      significantly more validated pain assessment tools (P<0.001) and had a greater
      proportion of patients who received analgesics (P=0.03) and physical pain
      management strategies (P=0.02). Mean pain intensity scores were significantly
      lower in the EPIQ group (P=0.03). Comparisons of moderate (4-6/10) and severe (7
      10/10) pain, controlling for child and unit level factors, indicated that the
      odds of having severe pain were 51% less for children in the EPIQ group (adjusted
      OR: 0.49, 95% CI: 0.26-0.83; P=0.009). EPIQ was effective in improving practice
      and clinical outcomes for hospitalized children. Additional exploration of the
      influence of contextual factors on research use in hospital settings is required
      to explain the variability in pain processes and clinical outcomes.

PMID- 24021863
TI  - Stress and visceral pain: focusing on irritable bowel syndrome.
AB  - Recent advances in brain science have shown that the brain function encoding
      emotion depends on interoceptive signals such as visceral pain. Visceral pain
      arose early in our evolutionary history. Bottom-up processing from gut-to-brain
      and top-down autonomic/neuroendocrine mechanisms in brain-to-gut signaling
      constitute a circuit. Brain imaging techniques have enabled us to depict the
      visceral pain pathway as well as the related emotional circuit. Irritable bowel
      syndrome (IBS) is characterized by chronic recurrent abdominal pain or abdominal
      discomfort associated with bowel dysfunction. It is also thought to be a disorder
      of the brain-gut link associated with an exaggerated response to stress.
      Corticotropin-releasing hormone (CRH), a major mediator of the stress response in
      the brain-gut axis, is an obvious candidate in the pathophysiology of IBS.
      Indeed, administration of CRH has been shown to aggravate the visceral
      sensorimotor response in IBS patients, and the administration of peptidergic CRH
      antagonists seems to alleviate IBS pathophysiology. Serotonin (5-HT) is another
      likely candidate associated with brain-gut function in IBS, as 5-HT3 antagonists,
      5-HT4 agonists, and antidepressants were demonstrated to regulate 5-HT
      neurotransmission in IBS patients. Autonomic nervous system function, the
      neuroimmune axis, and the brain-gut-microbiota axis show specific profiles in IBS
      patients. Further studies on stress and visceral pain neuropathways in IBS
      patients are warranted. 

PMID- 24021864
TI  - Ultrasound does not provide reliable results for the measurement of the patellar
      tendon cross sectional area.
AB  - PURPOSE: This study examined the reliability of patellar tendon cross sectional
      area (CSA) measurement using brightness mode ultrasonography. METHODS: The
      patellar tendon CSA of fourteen participants was examined on two different days
      and at three different positions (proximal, median and distal). Five trials per
      day were conducted in each position, replacing the ultrasound probe on every
      trial. The images were examined by three different and equally experienced
      observers. We compared the mean of the five trials in each position to examine
      the day, observer and position effect. Further, Bland and Altman plots, root mean
      square (RMS) differences and intraclass correlation coefficients (ICC) were
      calculated. RESULTS: There was a significant (p < 0.05) day, observer and
      position effect on the CSA, while the average ICC was 0.592. The Bland and Altman
      plots showed that differences between conditions or groups, should be in average
      lower than 37% or higher than 55% of the patellar tendon CSA to be important for
      clinical or intervention studies. CONCLUSION: Our findings show low reliability
      of the method, which resulted from the low clarity and unclear visibility of
      tissue boundaries in the ultrasound images. Therefore, the measurement of the CSA
      of the patellar tendon using ultrasound does not provide accurate and reliable
      results.

PMID- 24021865
TI  - In vitro assessment of the immunity of implantable cardioverter-defibrillators to
      magnetic fields of 50/60 Hz.
AB  - Public concern for the compatibility of electromagnetic (EM) sources with active
      implantable medical devices (AIMD) has prompted the development of new systems
      that can perform accurate exposure studies. EM field interference with active
      cardiac implants (e.g. implantable cardioverter-defibrillators (ICDs)) can be
      critical. This paper describes a magnetic field (MF) exposure system and the
      method developed for testing the immunity of ICD to continuous-wave MFs. The MFs
      were created by Helmholtz coils, housed in a Faraday cage. The coils were able to
      produce highly uniform MFs up to 4000 uT at 50 Hz and 3900 uT at 60 Hz, within
      the test space. Four ICDs were tested. No dysfunctions were found in the
      generated MFs. These results confirm that the tested ICDs were immune to low
      frequency MFs. 

PMID- 24021866
TI  - Why ligand cross-reactivity is high within peptide recognition domain families? A
      case study on human c-Src SH3 domain.
AB  - Many important protein-protein interactions in eukaryotic signaling networks are
      mediated by peptide recognition domains (PRDs), which bind short linear sequence
      motifs in other proteins. However, high ligand cross-reactivity is observed
      within most PRD families, rendering a broad specificity for the family members.
      In the present study, we attempt to explore the molecular mechanism and
      physicochemical origin of PRD cross-reactivity. In the procedure, a structure
      based method called atomic cross-nonbonded interaction analysis (ACNIA) is
      described to extract atomic-level nonbonded interaction information at domain
      peptide interface and to correlate the information with peptide affinity based on
      a set of structure-solved, affinity-known protein-peptide complex samples
      compiled from numerous literatures and databases. The ACNIA-derived affinity
      predictor is tested rigorously with statistical validation approach, which is
      also demonstrated to be capable of perceiving slight structural change in the
      interface using three distinct panels of SH3-binding peptide data. Subsequently,
      with help of the affinity predictor we adopt the human c-Src SH3 domain, one of
      the most sophisticated PRDs, as a paradigm to investigate the ligand cross
      reactivity within SH3 family. It is found that most of the family members have
      only few non-essential residue differences in their peptide-binding pockets, and
      thus exhibit a similar peptide recognition profile and high cross-reactivity. The
      cross-reactivity is even shared by different subclasses of SH3 domains. The
      findings suggest that inherent binding specificity is not the only factor to
      select appropriate binders for specific SH3 domains, and other aspects such as
      cellular context and the rest of the SH3-containing proteins may play important
      roles in reducing their ligand cross-reactivity. 

PMID- 24021867
TI  - Low complexity regions (LCRs) contribute to the hypervariability of the HIV-1
      gp120 protein.
AB  - Low complexity regions (LCRs) are sequences of nucleic acids or proteins defined
      by a compositional bias. Their occurrence has been confirmed in sequences of the
      three cellular lineages (Bacteria, Archaea and Eucarya), and has also been
      reported in viral genomes. We present here the results of a detailed computer
      analysis of the LCRs present in the HIV-1 glycoprotein 120 (gp120) encoded by the
      viral gene env. The analysis was performed using a sample of 3637 Env polyprotein
      sequences derived from 4117 completely sequenced and translated HIV-1 genomes
      available in public databases as of December 2012. We have identified 1229 LCRs
      located in four different regions of the gp120 protein that correspond to four of
      the five regions that have been identified as hypervariable (V1, V2, V4 and V5).
      The remaining 29 LCRs are found in the signal peptide and in the conserved
      regions C2, C3, C4 and C5. No LCR has been identified in the hypervariable region
      V3. The LCRs detected in the V1, V2, V4, and V5 hypervariable regions exhibit a
      high Asn content in their amino acid composition, which very likely correspond to
      glycosylation sites, which may contribute to the retroviral ability to avoid the
      immune system. In sharp contrast with what is observed in gp120 proteins lacking
      LCRs, the glycosylation sites present in LCRs tend to be clustered towards the
      center of the region forming well-defined islands. The results presented here
      suggest that LCRs represent a hitherto undescribed source of genomic variability
      in lentivirus, and that these repeats may represent an important source of
      antigenic variation in HIV-1 populations. The results reported here may exemplify
      the evolutionary processes that may have increased the size of primitive cellular
      RNA genomes and the role of LCRs as a source of raw material during the processes
      of evolutionary acquisition of new functions. 

PMID- 24021868
TI  - Speed dating, rejection, and finding the perfect mate: advice from flowering
      plants.
AB  - Angiosperm pollen tubes extend through pistil tissue to deliver a pair of
      immotile sperm cells to female gametes for double fertilization. The extended
      journey of the pollen tube requires extensive cell:cell interactions that guide
      the pollen tube to its destination and instruct it to stop growing and burst.
      Once sperm cells are released the molecular exchanges between male and female
      continue, resulting in sperm activation and gamete fusion. Finally, there is
      evidence that gamete fusion can feed back on the pollen tube attraction mechanism
      so that additional pollen tubes can be attracted only if the first sperm cells
      fail to fertilize. We review progress toward defining the molecules mediating
      each of these exchanges and describe how small cysteine-rich peptides are a major
      mode of cellular communication. 

PMID- 24021869
TI  - Ambient temperature signalling in plants.
AB  - Plants are exposed to daily and seasonal fluctuations in temperature. Within the
      'ambient' temperature range (about 12-27 degrees C for Arabidopsis) temperature
      differences have large effects on plant growth and development, disease
      resistance pathways and the circadian clock without activating temperature stress
      pathways. It is this developmental sensing and response to non-stressful
      temperatures that will be covered in this review. Recent advances have revealed
      key players in mediating temperature signals. The bHLH transcription factor
      PHYTOCHROME INTERACTING FACTOR4 (PIF4) has been shown to be a hub for multiple
      responses to warmer temperature in Arabidopsis, including flowering and hypocotyl
      elongation. Changes in chromatin state are involved in transmitting temperature
      signals to the transcriptome. Determining the precise mechanisms of temperature
      perception represents an exciting goal for the field. 

PMID- 24021870
TI  - Preparation of activated carbons from Iris tectorum employing ferric nitrate as
      dopant for removal of tetracycline from aqueous solutions.
AB  - Ferric nitrate was employed to modify activated carbon prepared from Iris
      tectorum during H3PO4 activation and ability of prepared activated carbon for
      removal of tetracycline (TC) was investigated. The properties of the activated
      carbon samples with or without ferric nitrate, ITAC-Fe and ITAC, were measured by
      scanning electron microscopy (SEM), N2 adsorption/desorption isotherms, Fourier
      transform infrared spectroscopy (FTIR) and Boehm's titration. The results showed
      that mixing with iron increased the BET surface area, total pore volume and the
      adsorption capacity as compared to the original carbon. FTIR and Boehm's
      titration suggested that ITAC-Fe was characteristic of more acidic functional
      groups than ITAC. Adsorption of TC on both samples exhibited a strong pH
      dependent behavior and adsorption capacity reduced rapidly with the increasing
      solution pH. The adsorption kinetics agreed well with the pseudo-second-order
      model and the adsorption isotherms data were well described by Langmuir model
      with the maximum adsorption capacity of 625.022 mg/g for ITAC and 769.231 mg/g
      for ITAC-Fe. The present work suggested that ITAC-Fe could be used to remove
      tetracycline effectively from aqueous solutions.

PMID- 24021871
TI  - Effects of heavy metals on antioxidants and expression of HSP70 in different
      tissues of Milk fish (Chanos chanos) of Kaattuppalli Island, Chennai, India.
AB  - Distribution of heavy metals and its associated oxidative stress, ultrastructure
      and expression of HSP 70 were studied in varies tissues of Chanos chanos
      collected from polluted sites compared with the fish collected from less polluted
      sites of Kaattuppalli Island. The concentrations of copper, lead, zinc, cadmium,
      manganese and iron were quantified in gills and liver. The results showed marked
      differences between the two sites as well as significant variations within the
      tissues. The decreasing trend of metals in the tissues of fish sampled from both
      polluted and less polluted sites was in the order of Fe>Mn>Zn>Cu>Pb>Cd. Overall,
      the highest metal concentrations were found in the fish collected from polluted
      sites. Similarly increase of antioxidant enzymes biomarkers due to heavy metals
      was also evident in gills and liver of the fish collected from polluted sites.
      These tissues were further investigated by scanning and electron microscopy and
      the results were compared with the reference less polluted sites. The presence of
      large lipid droplets in liver and increase of mucous cells in gills were some of
      the most noticeable alterations observed and were related to heavy metal
      contaminants. It is concluded that scanning, ultrastructural and useful of HSP70
      biomarkers for heavy metal induced oxidative stress, and demonstrate that
      precautions need to be taken in polluted sites of Kaattuppalli Island in order to
      prevent heavy metal pollution that can occur in the future. 

PMID- 24021872
TI  - Assessment of trace element concentrations in soil and plants from cropland
      irrigated with wastewater.
AB  - Samples of soil and food plants were collected from wastewater-irrigated fields
      in the vicinity of Gaziantep, in southeast Turkey, and analyzed for several trace
      elements (TEs). The concentrations of Co, Mo and Zn in edible portions of corn,
      mint and vegetables (eggplant, pepper and tomato) were 0.03-0.66, 0.1-3.2 and 8
      148 mg kg-1, respectively. In the edible portions of corn and mint, Cd, Cr, Cu,
      Ni and Pb concentrations in all samples were <0.01-0.05, 2.0-5.5, 6-47, 0.6-6.7
      and 0.2-3.5 mg kg-1, respectively. No single plant species had consistently high
      concentrations of all metals. For example, corn had the highest concentration of
      Zn (89 mg kg-1), but the lowest concentration of Cd (<0.01 mg kg-1). The maximum
      concentrations of some TEs in some crop samples, as well as soil samples,
      exceeded certain threshold values set in Turkey and other countries. For some TEs
      there was little difference between wastewater-irrigated and control soil
      concentrations. Transfer factors (TFs; plant concentration/soil concentration)
      were high for Cu, Zn and Mo, in comparison with the other TEs (Cd, Co, Cr, Ni and
      Pb). Higher uptake of certain metals may be associated with the dominant form of
      the element in the soil matrix. The uptake of chemicals to plant tissues is
      influenced by the chemical and physical characteristics of the soil and species
      specific factors. Although the geochemistry of the region plays a significant
      role in the levels of TEs in soil and plants, bioaccumulation of metals and
      subsequent toxicity to plants and animals can be exacerbated by higher
      environmental concentrations caused by wastewater irrigation and other
      anthropogenic factors.

PMID- 24021874
TI  - Lung clearance index predicts pulmonary exacerbations in young patients with
      cystic fibrosis.
AB  - RATIONALE: The lung clearance index (LCI) is a promising endpoint for use in
      cystic fibrosis (CF) clinical trials, but correlations with validated clinical
      endpoints have not yet been established. OBJECTIVE: This study aimed to
      demonstrate that, in young patients with CF, baseline LCI predicts subsequent
      pulmonary exacerbation (PE) and correlates with the respiratory domain of the CF
      Questionnaire-Revised (CFQ-Rresp). METHODS: Baseline LCI, forced expiratory
      volume in 1 s (FEV1), CFQ-Rresp and PEs over the subsequent year were
      prospectively recorded in 63 patients aged 5-19 years. The ability of baseline
      LCI to predict PE was assessed using negative binomial regression models and
      Kaplan-Meier plots. RESULTS: Twenty-six patients (41%) experienced 48 PEs.
      Baseline LCI and FEV1 were predictors of PE. Compared with the quartile with the
      lowest LCI, the annual PE rate in increasing LCI quartiles was 2.9 (95% CI 0.5 to
      16.5, p=0.238), 5.4 (95% CI 1.0 to 29.0, p=0.045) and 13.6 (95% CI 2.8 to 67.1,
      p=0.001). Similarly, time to first PE decreased with worsening LCI quartiles (log
      rank test for trend, p<0.001). Furthermore, LCI correlated with CFQ-Rresp (r=
      0.43, p<0.001). In the subgroup of 53 patients with normal FEV1, LCI was a
      predictor of PE. In this subgroup, LCI also correlated with CFQ-Rresp (r=-0.282,
      p=0.043). CONCLUSIONS: Baseline LCI predicts PE in young patients with CF and
      correlates with CFQ-Rresp, a validated patient-reported outcome, even in the
      subgroup with normal FEV1. These data further support the use of LCI as a
      surrogate outcome measure in CF clinical trials.

PMID- 24021875
TI  - Gene expression profiling using nanostring digital RNA counting to identify
      potential target antigens for melanoma immunotherapy.
AB  - PURPOSE: The success of immunotherapy for the treatment of metastatic cancer is
      contingent on the identification of appropriate target antigens. Potential
      targets must be expressed on tumors but show restricted expression on normal
      tissues. To maximize patient eligibility, ideal target antigens should be
      expressed on a high percentage of tumors within a histology and, potentially, in
      multiple different malignancies. DESIGN: A Nanostring probeset was designed
      containing 97 genes, 72 of which are considered potential candidate genes for
      immunotherapy. Five established melanoma cell lines, 59 resected metastatic
      melanoma tumors, and 31 normal tissue samples were profiled and analyzed using
      Nanostring technology. RESULTS: Of the 72 potential target genes, 33 were
      overexpressed in more than 20% of studied melanoma tumor samples. Twenty of those
      genes were identified as differentially expressed between normal tissues and
      tumor samples by ANOVA analysis. Analysis of normal tissue gene expression
      identified seven genes with limited normal tissue expression that warrant further
      consideration as potential immunotherapy target antigens: CSAG2, MAGEA3, MAGEC2,
      IL13RA2, PRAME, CSPG4, and SOX10. These genes were highly overexpressed on a
      large percentage of the studied tumor samples, with expression in a limited
      number of normal tissue samples at much lower levels. CONCLUSION: The application
      of Nanostring RNA counting technology was used to directly quantitate the gene
      expression levels of multiple potential tumor antigens. Analysis of cell lines,
      59 tumors, and normal tissues identified seven potential immunotherapy targets
      for the treatment of melanoma that could increase the number of patients
      potentially eligible for adoptive immunotherapy.

PMID- 24021876
TI  - Both mutated and unmutated memory B cells accumulate mutations in the course of
      the secondary response and develop a new antibody repertoire optimally adapted to
      the secondary stimulus.
AB  - High-affinity memory B cells are preferentially selected during secondary
      responses and rapidly differentiate into antibody-producing cells. However, it
      remains unknown whether only high-affinity, mutated memory B cells simply expand
      to dominate the secondary response or if in fact memory B cells with a diverse VH
      repertoire, including those with no mutations, accumulate somatic mutations to
      create a new repertoire through the process of affinity maturation. In this
      report, we took a new approach to address this question by analyzing the VH gene
      repertoire of IgG1(+) memory B cells before and after antigen re-exposure in a
      host unable to generate IgG(+) B cells. We show here that both mutated and
      unmutated IgG1(+) memory B cells respond to secondary challenge and expand while
      accumulating somatic mutations in their VH genes in a stepwise manner. Both types
      of memory cells subsequently established a VH gene repertoire dominated by two
      major clonotypes, which are distinct from the original repertoire before antigen
      re-exposure. In addition, heavily mutated memory B cells were excluded from the
      secondary repertoire. Thus, both mutated and unmutated IgG1(+) memory cells
      equally contribute to establish a new antibody repertoire through a dynamic
      process of mutation and selection, becoming optimally adapted to the recall
      challenge.

PMID- 24021877
TI  - DEC-205-mediated antigen targeting to steady-state dendritic cells induces
      deletion of diabetogenic CD8+ T cells independently of PD-1 and PD-L1.
AB  - CD8+ T cells specific for islet-specific glucose-6-phosphatase catalytic subunit
      related protein (IGRP) have been implicated in type 1 diabetes in both humans and
      non-obese diabetic (NOD) mice, in which T cells specific for IGRP206-214 are
      highly prevalent. We sought to manipulate these pathogenic T cells by exploiting
      the ability of steady-state dendritic cells (DCs) to present antigens in a
      tolerogenic manner. The endocytic receptor DEC-205 was utilized to deliver an
      IGRP206-214 mimotope to DCs in NOD mice, and the impact of this delivery on a
      polyclonal population of endogenous islet-reactive cognate T cells was
      determined. Assessment of islet-infiltrating CD8+ T cells showed a decrease in
      the percentage, and the absolute number, of endogenous IGRP206-214-specific T
      cells when the mimotope was delivered to DCs, compared with delivery of a
      specificity control. Employing an adoptive transfer system, deletion of CD8+ T
      cells as a result of DEC-205-mediated antigen targeting was found to occur
      independently of programmed death-1 (PD-1) and its ligand (PD-L1), both often
      implicated in the regulation of peripheral T-cell tolerance. Given its promise
      for the manipulation of self-reactive polyclonal T cells demonstrated here, the
      distinctive characteristics of this antigen delivery system will be important to
      appreciate as its potential as an intervention for autoimmune diseases continues
      to be investigated.

PMID- 24021878
TI  - The relationship between psychotic symptoms and social functioning in a non
      clinical population of 12year olds.
AB  - BACKGROUND: Psychotic symptoms are common in adolescents in the general
      population but it is unknown whether they are associated with poor social
      functioning. AIMS: To investigate whether adolescent psychotic symptoms are
      associated with poor social functioning measured by peer relationships. METHOD:
      Data from the Avon Longitudinal Study of Parents and Children cohort was used.
      Logistic regression was used to explore the relationship between psychotic
      symptoms at 12.9years detected using a semi-structured interview and poor social
      functioning at 13.2years using parent-reported peer problems from the Strengths
      and Difficulties Questionnaire. RESULTS: There was strong evidence (p<0.001) of
      an unadjusted association between psychotic symptoms and poor social functioning
      (OR 1.41, 95% CI 1.24-1.61). The association was attenuated after adjusting for
      earlier social functioning, socio-demographic variables, bullying status and IQ
      (OR 1.28, 95% CI 1.09-1.50). The majority of the crude association was explained
      by additional adjustment for emotional problems including depression at age 12,
      emotional symptoms, hyperactivity and conduct problems at age 11 (OR 1.07, 95% CI
      0.89-1.29). CONCLUSION: Adolescents with psychotic symptoms may be no more likely
      to have poor social functioning than other adolescents, once other emotional
      problems have been taken into account. The discussion addressed two explanations.
      First, emotional problems may be on the causal pathway from psychotic symptoms to
      poor social functioning. Alternatively, emotional symptoms may act as a
      confounder, suggesting that medical intervention may be inappropriate. It is the
      impact of psychotic symptoms on the individual that should dictate whether any
      intervention is required.

PMID- 24021879
TI  - Disappearance of the unmasking effect of temporally pre-presented lipreading cues
      on speech recognition in people with chronic schizophrenia.

PMID- 24021880
TI  - The true nature of atypical breast cytology.
AB  - BACKGROUND: Atypical breast cytology is a poorly understood heterogeneous
      category with limited clinical utility but significant implications for patient
      management. OBJECTIVE: To provide an insight into the true nature of atypical
      breast cytology in screening-detected (asymptomatic) and symptomatic settings,
      and find strategies for reducing the use of this diagnostic category. MATERIALS
      AND METHODS: A total of 6,415 breast cytology samples were processed between
      January 2004 and December 2008. An atypical cytological diagnosis was rendered in
      256 (4%) of the cases. A blind microscopic review of the atypical cases was
      conducted and results were correlated with subsequent histological and/or
      clinical outcomes. RESULTS: Follow-up information by histology was available in
      85.5%, by repeat fine-needle aspiration (FNA) in 3.5% and by imaging or clinical
      follow-up in 10.2% of the cases. Two patients (0.8%) were lost to follow-up. Of
      the 254 cases with follow-up, 62.6% were benign and 37.4% were malignant. The
      benign to malignant ratios were 1:1 and 2:1 in the screening and symptomatic
      groups, respectively. The atypical category in the screening population mostly
      yielded fat necrosis, complex sclerosing lesions and low- to intermediate-grade
      carcinoma on follow-up. The main outcomes in the symptomatic group were
      papilloma, fibroadenoma, ductal carcinoma in situ and lobular carcinoma.
      Preanalytical (suboptimal samples) factors were encountered in 34.8% and
      interpretative factors in 65.2% of the cases. Uncertainty about cellular
      morphology was attributed to such a diagnosis in 38 (14.8%) of the cases,
      architectural complexity in 137 (53.5%) and morphology and architecture in 70
      (27.3%); 4.3% of cases were considered nondiagnostic. CONCLUSION: The atypical
      category is a necessary diagnosis but of limited use from a patient management
      perspective. Some preanalytical factors such as poor sample quality can be
      minimized by the involvement of cytopathologists in the FNA procedure. The use of
      the atypical category is partly dependent on the experience and confidence of the
      reporting pathologist. Assigning a case to this category is also likely to be
      unduly influenced by clinical or radiological findings. Our study indicates that
      the use of the atypical category can be reduced by up to 40% by appreciating
      these contributing factors. The practical utilization of the atypical category in
      breast cytology remains subjective and further study is required to identify
      useful objective criteria.

PMID- 24021881
TI  - Crossover fungal pathogens: the biology and pathogenesis of fungi capable of
      crossing kingdoms to infect plants and humans.
AB  - The outbreak of fungal meningitis associated with contaminated methylprednisolone
      acetate has thrust the importance of fungal infections into the public
      consciousness. The predominant pathogen isolated from clinical specimens,
      Exserohilum rostratum (teleomorph: Setosphaeria rostrata), is a dematiaceous
      fungus that infects grasses and rarely humans. This outbreak highlights the
      potential for fungal pathogens to infect both plants and humans. Most crossover
      or trans-kingdom pathogens are soil saprophytes and include fungi in Ascomycota
      and Mucormycotina phyla. To establish infection, crossover fungi must overcome
      disparate, host-specific barriers, including protective surfaces (e.g. cuticle,
      skin), elevated temperature, and immune defenses. This review illuminates the
      underlying mechanisms used by crossover fungi to cause infection in plants and
      mammals, and highlights critical events that lead to human infection by these
      pathogens. Several genes including veA, laeA, and hapX are important in
      regulating biological processes in fungi important for both invasive plant and
      animal infections. 

PMID- 24021883
TI  - Characterization of antigenic domains and epitopes in the ORF3 protein of a
      Chinese isolate of avian hepatitis E virus.
AB  - Avian hepatitis E virus (HEV) is an emerging virus associated with the big liver
      and spleen disease or hepatitis-splenomegaly syndrome in chickens and subclinical
      infections by the virus are also common. The complete genome of avian HEV
      contains three open-reading frames (ORFs) in which ORF2 protein is part of virus
      particles and thus contains primary epitopes. Antigenic epitopes of avian HEV
      ORF2 protein have been described but those associated with the ORF3 have not. To
      analyze the antigenic domains and epitopes in the ORF3 protein of a Chinese
      isolate of avian HEV (CaHEV), we generated a series of antigens comprised of the
      complete ORF3 and also five truncated overlapping ORF3 peptides. The antibodies
      used in this study were mouse antisera and monoclonal antibodies against ORF3,
      positive chicken sera from Specific Pathogen Free chickens experimentally
      infected with CaHEV and clinical chicken sera. Using these antigens and
      antibodies, we identified three antigenic domains at amino acids (aa) 1-28, 55-74
      and 75-88 in which aa 75-88 was a dominant domain. The dominant domain contained
      at least two major epitopes since field chickens infected with avian HEV produced
      antibodies against the domain and epitopes. These results provide useful
      information for future development of immunoassays for the diagnosis of avian HEV
      infection. 

PMID- 24021884
TI  - Non-pet dogs as sentinels and potential synanthropic reservoirs of tick-borne and
      zoonotic bacteria.
AB  - Blood samples were collected from 100 shepherd dogs, 12 hunting dogs and 14 stray
      dogs (apparently healthy) in southern Hungary to screen for the presence of
      emerging tick-borne pathogens. Based on real-time PCR results, 14 dogs (11%) had
      single or dual haemoplasma infection, and a same number of samples were positive
      for Anaplasma phagocytophilum. In one sample Coxiella burnetii was molecularly
      identified, and 20.3% of dogs seroconverted to the Q fever agent. Rickettsaemia
      (sensu stricto) was also detected in one animal. This is the first molecular
      evidence of autochthonous infection of dogs with the above pathogens in Hungary.
      The relatively high prevalence of haemoplasma and anaplasma infection among non
      pet dogs is suggestive of a prolonged carrier status and bacteraemia of these
      animals rendering them epidemiologically significant as potential reservoirs and
      sentinels for tick-borne infections. 

PMID- 24021885
TI  - Mitochondria-targeted antioxidant peptide SS31 prevents hypoxia/reoxygenation
      induced apoptosis by down-regulating p66Shc in renal tubular epithelial cells.
AB  - BACKGROUND/AIMS: Ischemia/reperfusion injury plays a crucial role in renal
      transplantation and represents a significant risk factor for acute kidney injury
      and delayed graft function. Mitochondria-targeted antioxidant peptide SS31 has
      been shown to attenuate ischemia/reperfusion injury by inhibiting oxidative
      stress. The present study was carried out to investigate whether the pretreatment
      of SS31 could reduce hypoxia/reoxygenation (H/R)-induced injury by inhibiting
      p66Shc. METHODS: The cultured rat renal proximal tubular cell line NRK52E cells
      were exposed to 24 h hypoxia (5% CO2, 1% O2, 94% N2) followed by 6 h
      reoxygenation (5% CO2, 21% O2, 74% N2). SS31 was added to the culture medium 4 h
      prior to the treatment. Then the cell viability, apoptosis, and oxidative stress
      levels were determined. In addition, western blot analysis was performed to
      determine the expression of p66Shc, p-p66Shc, cytochrome c, and caspase-3.
      RESULTS: H/R induced apoptotic cell death, accompanied with activation of total
      and p-p66Shc in NRK52E cells. Pretreatment with SS31 or overexpression of a
      dominantnegative Ser36 mutant p66Shc (p66Shc S36A) or p66Shc siRNA prevented cell
      death, whereas the protection effect of SS31 was completely blocked by
      overexpression of wild-type p66Shc. Furthermore, SS31 pretreatment reduced H/R
      induced intracellular oxidative stress, cytochrome c translocation to the
      cytoplasm, and caspase-3 activation through inhibiting p66Shc. CONCLUSION: This
      study revealed that SS31 pretreatment serves a protective role against H/R
      induced apoptosis of human renal tubular epithelial cells, and the mechanism is
      related to suppression of p66Shc.

PMID- 24021886
TI  - What can we learn from Einstein and Arrhenius about the optimal flow of our
      blood?
AB  - BACKGROUND: The oxygen flow in humans and other higher animals depends on the
      erythrocyte-to-blood volume ratio, the hematocrit. Since it is physiologically
      favourable when the flow of oxygen transport is maximum it can be assumed that
      this situation has been achieved during evolution. If the hematocrit was too low,
      too few erythrocytes could transport oxygen. If it was too high, the blood would
      be very viscous, so that oxygen supply would again be reduced. METHODS: The
      theoretical optimal hematocrit can be calculated by considering the dependence of
      blood viscosity on the hematocrit. Different approaches to expressing this
      dependence have been proposed in the literature. Here, we discuss early
      approaches in hydrodynamics proposed by Einstein and Arrhenius and show that
      especially the Arrhenius equation is very appropriate for this purpose. RESULTS &
      CONCLUSIONS: We show that despite considerable simplifications such as neglecting
      the deformation, orientation and aggregation of erythrocytes, realistic
      hematocrit values of about 40% can be derived based on optimality considerations.
      Also the prediction that the ratio between the viscosities of the blood and blood
      plasma at high shear rates nearly equals Euler's constant (2.718) is in good
      agreement with observed values. Finally, we discuss possible extensions of the
      theory. For example, we derive the theoretical optimal hematocrit for persevering
      divers among marine mammals to be 65%, in excellent agreement with the values
      observed in several species. GENERAL SIGNIFICANCE: These considerations are very
      important for human and animal physiology since oxygen transport is an important
      factor for medicine and physical performance.

PMID- 24021888
TI  - Roles of microRNAs in pressure overload- and ischemia-related myocardial
      remodeling.
AB  - Cardiac remodeling, a term that spans maladaptation at the molecular, cellular,
      tissue and organ levels, is the key pathophysiological process that leads to
      heart failure (HF). In clinic, pressure overload and ischemia are the two most
      common reasons to induce cardiac remodeling and HF, which includes but is not
      limited to cardiac hypertrophy, fibrosis, and cardiomyocyte apoptosis. MicroRNAs
      (miRNAs) are endogenous, single-stranded, short non-coding RNAs. By imperfectly
      binding to the 3' untranslated region (UTR) of messenger RNAs (mRNAs), miRNAs are
      able to suppress target gene expression by promoting degradation or by inhibiting
      translation of the target mRNAs, thus playing an important role in a wide range
      of biologic processes. Growing evidence has indicated that miRNAs are aberrantly
      expressed in the cardiovascular system under experimental and clinical conditions
      with cardiac remodeling and HF. Clinically there is increasing evidence that
      miRNAs can act as diagnostic biomarker and even represent a novel therapeutic
      target in several cardiovascular disorders. This review provides an overview of
      several miRNAs' impacts in pressure-overload and ischemia-induced cardiac
      remodeling and HF. 

PMID- 24021889
TI  - The effect of acitretin treatment on insulin resistance, retinol-binding protein
      4, leptin, and adiponectin in psoriasis vulgaris: a noncontrolled study.
AB  - BACKGROUND/AIM: To investigate the effects of acitretin treatment on insulin
      resistance (IR) and adipokines, particularly retinol-binding protein (RBP)-4.
      METHODS: Thirty-four patients with chronic plaque psoriasis and a control group
      of 34 healthy volunteers were recruited in the study. Screening for the
      parameters was performed before starting and after 3 months of acitretin
      treatment in the psoriasis group. The control group was only evaluated at the
      beginning of the study and did not receive placebo. We could not compare our
      results with a placebo control group because of ethical reasons. RESULTS: Basal
      adiponectin (p = 0.01), insulin (p < 0.0001) levels and homeostasis model
      assessment (HOMA) IR (p < 0.0001) were significantly higher in psoriasis
      patients. After the treatment, insulin (p = 0.014), C peptide (p = 0.011), RBP-4
      (p < 0.0001) levels and HOMA-IR (p = 0.008) decreased significantly.
      Posttreatment leptin (p = 0.036) levels were significantly lower than those of
      the controls. Posttreatment adiponectin (p = 0.005) and insulin (p = 0.048)
      levels were higher than those of the controls. CONCLUSIONS: This study showed for
      the first time that RBP-4 levels and IR are decreased significantly with
      acitretin treatment. This finding is very important in psoriasis patients because
      psoriasis may cause insulin resistance and diabetes. Further experimental and
      clinical studies are needed to clarify the effect of acitretin on adipocyte
      structure and behavior.

PMID- 24021887
TI  - Detection of electrophile-sensitive proteins.
AB  - BACKGROUND: Redox signaling is an important emerging mechanism of cellular
      function. Dysfunctional redox signaling is increasingly implicated in numerous
      pathologies, including atherosclerosis, diabetes, and cancer. The molecular
      messengers in this type of signaling are reactive species which can mediate the
      post-translational modification of specific groups of proteins, thereby effecting
      functional changes in the modified proteins. Electrophilic compounds comprise one
      class of reactive species which can participate in redox signaling. Electrophiles
      modulate cell function via formation of covalent adducts with proteins,
      particularly cysteine residues. SCOPE OF REVIEW: This review will discuss the
      commonly used methods of detection for electrophile-sensitive proteins, and will
      highlight the importance of identifying these proteins for studying redox
      signaling and developing novel therapeutics. MAJOR CONCLUSIONS: There are several
      methods which can be used to detect electrophile-sensitive proteins. These
      include the use of tagged model electrophiles, as well as derivatization of
      endogenous electrophile-protein adducts. GENERAL SIGNIFICANCE: In order to
      understand the mechanisms by which electrophiles mediate redox signaling, it is
      necessary to identify electrophile-sensitive proteins and quantitatively assess
      adduct formation. Strengths and limitations of these methods will be discussed.
      This article is part of a Special Issue entitled Current methods to study
      reactive oxygen species - pros and cons and biophysics of membrane proteins.
      Guest Editor: Christine Winterbourn.

PMID- 24021890
TI  - Synthesis and antibacterial activity of novel modified 5-O-mycaminose 14-membered
      ketolides.
AB  - A practicable method of introducing a side chain to the C-4' position of 5-O
      desosamine in the 14-membered ketolides was developed. And using this method, a
      series of novel modified 5-O-mycaminose ketolides were synthesized. These
      ketolides containing 5-O-4'-carbamate mycaminose were evaluated for their in
      vitro antibacterial activities against some respiratory pathogens. 15b and 18e
      showed comparable activity to telithromycin and clarithromycin.

PMID- 24021891
TI  - Synthesis and cytotoxic activity of some novel steroidal C-17 pyrazolinyl
      derivatives.
AB  - Fourteen novel steroidal C-17 pyrazolinyl derivatives 9a-g and 10a-g were
      synthesized from commercially available progesterone and tested for their
      cytotoxic activity against brine shrimp (Artemia salina) and three human cancer
      cell lines (NCI-H460, HeLa, and HepG2). Some of these synthetic compounds
      exhibited significant cytotoxic activity, and treatment of HeLa cells with
      compound 10b resulted in the cell population arrest in the S phase. A structure
      activity relationship was discussed. 

PMID- 24021892
TI  - Characterizing cardiopulmonary arrest during interventional radiology procedures.
AB  - PURPOSE: Careful case selection and preparation can prevent most cardiopulmonary
      arrest (CPA) in the interventional radiology (IR) suite. A series of CPAs was
      analyzed to provide insight into risk factors for these events. MATERIALS AND
      METHODS: A single-institution CPA database was used to identify all code team
      activations from January 1, 2005, to May 30, 2011, in the IR department. Medical
      records were searched for medical history, American Society of Anesthesiologists
      (ASA) classification, moderate sedation, and outcomes. Procedural data and
      procedure classification was acquired from the HI-IQ database. RESULTS: There
      were 36,489 procedures and 23 CPAs during the study period. Of the 23 patients
      with CPAs, 12 (52%) were male and 11 (48%) female, and average age was 57 years
      +/- 19 (standard deviation). Risk factors included a 56% incidence of diabetes
      mellitus, 48% incidence of hypertension, and 78% incidence of renal failure. Of
      the patients with kidney disease, 56% were chronically dialysis-dependent, and an
      additional 9% were undergoing central venous catheter placement for new
      hemodialysis. Seventy-eight percent had ASA status of III or greater, and 57%
      underwent moderate sedation during the procedure. Relative risk of a CPA during
      dialysis shunt interventions versus arterial interventions was 3.6 (95%
      confidence interval, 1.0-11.3; P = .045). Eight of 23 (35%) died: one (12%)
      during resuscitation and seven (88%) after resuscitation (P = .070). CONCLUSIONS:
      The most common comorbidity of patients with CPA in IR was kidney disease, and
      the most patients who had CPA underwent dialysis access-related procedures.

PMID- 24021893
TI  - Relationships between the mechanomyographic amplitude patterns of response and
      concentric isokinetic fatiguing tasks of the leg extensors.
AB  - The purpose of the present study was to examine possible correlations between the
      b terms (slopes) form the log-transformed mechanomyographic amplitude (MMGRMS)
      force relationships and the fatigue index calculated from 50 maximal concentric
      contractions. Forty healthy subjects (age = 21 +/- 2 yr) performed isometric ramp
      contractions from 5% to 85% of their maximal voluntary contraction followed by a
      50-repetition concentric fatigue protocol of the leg extensors, fatigue index (%)
      was calculated from the 50-repetitions. MMG was recorded during the ramp
      contractions from the vastus lateralis (VL) and rectus femoris (RF). The b terms
      (slopes) were calculated from the log-transformed MMGRMS-force relationships.
      Correlations were performed comparing the b terms from the MMGRMS-force
      relationships for the VL and RF with the fatigue index. Significant positive
      correlations were found among the b terms from the MMGRMS-force relationships for
      the VL (p = 0.007, r = 0.417) and RF (p = 0.014, r = 0.386) with the fatigue
      index. The b terms from the log-transformed MMGRMS-force relationships for the VL
      and RF may have reflected muscle fiber type composition and, thus, correlated
      with the fatigue index. This adds further support that the MMGRMS-force
      relationships may reflect muscle fiber type composition. 

PMID- 24021894
TI  - Risk of pseudophakic retinal detachment in 202,226 patients using the fellow
      nonoperated eye as reference.
AB  - PURPOSE: To study the risk of pseudophakic retinal detachment (PRD) after first
      eye phacoemulsification cataract surgery in Denmark relative to the risk of
      retinal detachment (RD) in the patients' fellow nonoperated eyes. DESIGN:
      Register-based cohort study. PARTICIPANTS: Danish patients (n = 202 226).
      METHODS: All patients underwent uncomplicated first-eye phacoemulsification
      cataract surgery from 2000 through 2010. Surgeries were identified via the
      National Patient Registry in Denmark and the Civil Registration Number. The
      fellow nonoperated eye was used as a reference. MAIN OUTCOME MEASURES:
      Rhegmatogenous RD. RESULTS: We identified 110 RDs in the fellow nonoperated
      reference eyes. In these eyes, male sex and younger age were associated
      significantly with greater risk of RD. We identified 465 PRDs on the cataract
      operated eyes. The relative risk of PRD was 4.23. This effect of cataract surgery
      on the relative risk of RD (the PRD risk ratio) was not statistically
      significantly modified by sex and age. The PRD risk ratio was not significantly
      higher in men compared with women (hazard ratio, 1.26); was highest for the 40
      year-old cohort and lowest for the 80-year-old cohort; and was highly increased
      during the first 6 months after surgery and leveled off but remained
      significantly elevated up to 10 years after cataract surgery. CONCLUSIONS: Using
      the fellow nonoperated eye as a reference, this comprehensive matched-design
      cohort study clearly separates the epidemiologic factors of occurrence of RD from
      the relative risk of PRD. The epidemiologic factors of RD in the fellow eyes was
      predicted strongly by age and sex. The 4-fold increase in risk associated with
      cataract surgery, the PRD risk ratio, was not statistically significantly
      modified by gender and age. The long follow-up demonstrated a persistently
      significantly elevated relative risk of PRD up to 10 years after cataract
      surgery. Because the fellow eye was used as reference, the PRD risk ratio can be
      considered a true etiologic effect of cataract surgery.

PMID- 24021895
TI  - Assessment of choroidal thickness and volume during the water drinking test by
      swept-source optical coherence tomography.
AB  - OBJECTIVE: To evaluate changes in peripapillary and macular choroidal thickness
      and volume after the water-drinking test (WDT) using swept-source optical
      coherence tomography (SS OCT). DESIGN: Prospective, cross-sectional,
      observational study. PARTICIPANTS: Fifty-six eyes of 28 healthy volunteers.
      METHODS: Participants underwent a 3-dimensional optic disc and macula scanning
      protocol with a prototype SS OCT (Topcon, Inc., Tokyo, Japan) at baseline and 15,
      30, 45, and 120 minutes after the start of the WDT. The WDT consisted of drinking
      1000 ml of water within 5 minutes. Objective measurements of the choroid were
      obtained with automated segmentation of the choroidal boundaries. MAIN OUTCOME
      MEASURES: Choroidal thickness and volume. RESULTS: Mean age +/- standard
      deviation of participants was 35.6 +/- 9.1 years. Intraocular pressure (IOP)
      increased from 14.9 +/- 2.7 mmHg at baseline to a peak of 16.8 +/- 3.0 mmHg 15
      minutes after the WDT (P < 0.001). Mean baseline choroidal thickness and volume
      were 181.3 +/- 50.8 MUm and 6.19 +/- 1.80 mm(3), respectively, at the optic disc
      and 217.4 +/- 43.6 MUm and 7.83 +/- 1.55 mm(3), respectively, at the macula.
      After the WDT, peripapillary and macular choroidal thickness increased by a
      maximum of 5.7% (P<0.001) and 4.3% (P<0.001), respectively. Choroidal volumes
      increased by 6.4% (P<0.001) and 3.9% (P<0.001), respectively. There was no
      association between change in IOP and peripapillary (P = 0.27) or macular (P =
      0.09) choroidal thickness. CONCLUSIONS: Using automated segmentation of SS OCT
      measurements, significant increases in choroidal thickness and volume are
      observed after the WDT in healthy subjects.

PMID- 24021896
TI  - Bromfenac ophthalmic solution 0.07% dosed once daily for cataract surgery:
      results of 2 randomized controlled trials.
AB  - PURPOSE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic
      solution 0.07% (Prolensa) dosed once daily for the treatment of ocular
      inflammation and pain in subjects who underwent cataract surgery with posterior
      chamber intraocular lens implantation. DESIGN: Two phase 3, randomized, double
      masked, placebo-controlled, multicenter clinical trials. PARTICIPANTS: Four
      hundred forty subjects (440 study eyes: 222 in the bromfenac group and 218 in the
      placebo group). METHODS: Two phase 3, prospective, randomized, double-masked,
      placebo-controlled clinical trials were conducted at 39 ophthalmology clinics in
      the United States. Subjects 18 years of age or older were randomized to receive
      either bromfenac 0.07% or placebo dosed once daily beginning 1 day before
      cataract surgery, on the day of surgery, and continuing for 14 days after surgery
      (for a total of 16 days). Subjects were evaluated on days 1, 3, 8, 15, and 22
      after surgery. The primary efficacy end point was cleared ocular inflammation, as
      measured by the summed ocular inflammation score of zero (anterior chamber cell
      count = 0 and absence of flare) by day 15. Secondary end points included cleared
      ocular inflammation at day 15 and the number of subjects who were pain free at
      day 1. The data from the 2 clinical trials were integrated for analyses. MAIN
      OUTCOME MEASURES: Summed ocular inflammation score and ocular pain. RESULTS: A
      significantly higher proportion of subjects treated with bromfenac 0.07% achieved
      complete clearance of ocular inflammation by day 15 and at day 15 compared with
      placebo (P < 0.0001). A statistically significantly higher proportion of subjects
      in the bromfenac 0.07% group were pain free at all study visits compared with
      those in the placebo group (P < 0.0001). Fewer subjects in the bromfenac group
      (3.2%) discontinued investigational product early because of a lack of efficacy
      than in the placebo group (23.9%; P < 0.0001). The incidence of adverse events
      was significantly lower in the bromfenac 0.07% group compared with the placebo
      group (P = 0.0041). CONCLUSIONS: Bromfenac ophthalmic solution 0.07% dosed once
      daily was clinically safe and effective compared with placebo for the treatment
      of ocular inflammation and pain in subjects who had undergone cataract surgery
      and may be a beneficial addition to the current standard of care, which commonly
      includes ophthalmic antibiotics and corticosteroids.

PMID- 24021897
TI  - Bizarre Stromal Cells in the Esophagus: A New Case.
AB  - Esophageal bizarre stromal cells (BSCs) represent an important diagnostic
      pitfall, since they can closely resemble a malignancy, thus leading to a
      significant overtreatment. We recently encountered a case in a healthy 38-year
      old man, with a normal blood count, who underwent an upper gastrointestinal
      endoscopy during the follow-up of a grade I esophagitis and hiatus hernia. The
      endoscopy revealed an ulcerated sessile polyp that, on histology, consisted of a
      proliferation of round atypical discohesive cells, with a variable amount of
      cytoplasm, large nuclei, and prominent eosinophilic nucleoli. They were
      intermingled with many granulocytes and plump vessels, in a background of
      granulation tissue. Immunohistochemical stains with pan-cytokeratin, S100, and
      CD31 were negative and Ki67 stained only very few nuclei. At variance with other
      anatomical sites and despite the putative fibroblastic or myofibroblastic origin,
      BSCs in esophagus can have a striking epithelioid appearance, mimicking a
      carcinoma or a melanoma. Awareness of BSCs can prevent serious misdiagnoses. 

PMID- 24021898
TI  - Adult rhabdomyoma of the extremity.
AB  - Adult rhabdomyoma is a rare benign tumor. It mainly occurs in the head and neck
      region and rarely occurs outside the head and neck region. We present an
      extremely rare case of the adult rhabdomyoma arising in the left foot in a 46
      year-old male. Microscopically, large polygonal cells and large strap-shaped
      cells were observed. This is the third case of adult rhabdomyoma arising in an
      extremity. 

PMID- 24021899
TI  - Histopathological changes in the gastrointestinal tract due to drugs: an update
      for the surgical pathologist (part I of II).
AB  - Abnormalities of the gastrointestinal (GI) tract due to drugs (AGIDs) are
      numerous and have significant impact. The aim of this narrative review is to help
      the practicing surgical pathologist recognize selected AGIDs. The adverse drug
      effects presented were chosen with an emphasis on recent and significant
      pathological and clinical contributions. The selection was based on a thorough
      review of the PUBMED-based literature and on the authors' opinions and
      experience. In the first part of the review, diagnostic abnormalities due to
      crystals (eg, iron, biphosphonates, nonsystemic drugs), mitosis arresting drugs
      (colchicine, taxanes), and biological agents, especially ipilimumab, are
      discussed. Some AGIDs' histopathologic features can be easily recognized. It is
      however the clinical correlation that in many cases of AGIDs will provide the
      necessary support for a drug effect diagnosis. The identification of AGIDs
      requires heightened awareness of the medical team in which close collaboration of
      pathologists and clinicians cannot be overemphasized. 

PMID- 24021900
TI  - Histopathological changes in the gastrointestinal tract due to medications: an
      update for the surgical pathologist (part II of II).
AB  - In keeping with the stated goal of providing the surgical pathologist with tools
      to recognize abnormalities of the gastrointestinal (GI) tract due to drugs
      (AGIDS), in part II of this review we embark in a more organ-based description of
      AGIDS. Adequate space is given to the numerous adverse gastrointestinal effects
      of nonsteroidal anti-inflammatory drugs. Pill esophagitis, esophagitis dissecans,
      proton pump inhibitors' effects, diaphragm disease, and the recently described
      effects of drugs such as olmesartan, mycophenolate, and of compounds such as
      yttrium-90 are highlighted among several others. The inclusion of drug effects in
      the differential diagnosis of "conventional" diseases (such as gastric antral
      vascular ectasia, graft-versus-host disease, ischemic colitis, acute colitis,
      collagenous enteritis, inflammatory bowel disease) is underscored to avoid
      sometimes significant diagnostic pitfalls. We reiterate the message of the
      necessary collaboration between pathologist and clinician in the recognition of
      these entities to provide the best patient care.

PMID- 24021901
TI  - Endosalpingiosis in axillary lymph nodes simulating metastatic breast carcinoma:
      a potential diagnostic pitfall.
AB  - Intraoperative assessment of sentinel lymph nodes at time of surgical excision of
      primary breast carcinoma is a crucial step in the determination of cancer extent
      and the need for further axillary dissection. Benign epithelial inclusions in
      axillary lymph nodes can mimic metastatic carcinoma and are a well-known pitfall
      during examination of these nodes in frozen or permanent sections. Most often,
      these inclusions consists of heterotopic mammary glands and are familiar to the
      practicing pathologist. Here, however, we present a rare case of endosalpingiosis
      in the axillary lymph nodes of a breast cancer patient and describe our
      experience and effort to characterize the lesion. Simulating a metastatic focus
      of invasive ductal carcinoma, the glandular inclusions lacked myoepithelial cells
      and failed to stain with myoepithelial markers. However, consistent with a
      Mullerian origin, the inclusions demonstrated strong staining with PAX-8 and WT
      1. Although endosalpingiotic inclusions are not uncommonly encountered in
      subdiaphragmatic lymph nodes, they are an extremely rare finding above the
      diaphragm. Pathologists must be aware of these lesions and their ability to
      imitate metastatic gland-forming carcinoma during frozen section or permanent
      examination of axillary lymph nodes. 

PMID- 24021902
TI  - The FUN of identifying gene function in bacterial pathogens; insights from
      Salmonella functional genomics.
AB  - The availability of thousands of genome sequences of bacterial pathogens poses a
      particular challenge because each genome contains hundreds of genes of unknown
      function (FUN). How can we easily discover which FUN genes encode important
      virulence factors? One solution is to combine two different functional genomic
      approaches. First, transcriptomics identifies bacterial FUN genes that show
      differential expression during the process of mammalian infection. Second, global
      mutagenesis identifies individual FUN genes that the pathogen requires to cause
      disease. The intersection of these datasets can reveal a small set of candidate
      genes most likely to encode novel virulence attributes. We demonstrate this
      approach with the Salmonella infection model, and propose that a similar strategy
      could be used for other bacterial pathogens. 

PMID- 24021904
TI  - Metastases to the pancreas diagnosed by fine-needle aspiration.
AB  - BACKGROUND: Metastatic cancer infrequently involves the pancreas. When the
      pancreas hosts a metastatic tumor, cytopathological evaluation of fine-needle
      aspirate material is a crucial part of the diagnostic process. In this study, we
      show two institutions' experience with cytopathological diagnosis of pancreatic
      metastasis. METHODS: Databases of institutional experience at The Johns Hopkins
      Hospital and Ohio State University Medical Center were queried for cases of
      metastatic tumors in the pancreas that underwent fine-needle aspiration.
      Demographic and pathological features were compiled and the cytomorphology was
      reviewed. RESULTS: Forty-two cases of tumor metastasis to the pancreas were
      found. Over the time of this review, 5,495 aspirates were performed, and 43%
      (2,389/5,495) had malignant cytological findings. Thus, the 42 cases of
      metastatic disease to the pancreas comprised 0.8% of all pancreas aspirates and
      1.8% of the malignant ones. Renal cell carcinoma was the most common metastasis,
      followed by melanoma and non-small cell lung carcinoma. Among the other tumors in
      this series, 2 cases each of rare metastases such as the fibrolamellar variant of
      hepatocellular carcinoma and solitary fibrous tumor were also seen. CONCLUSION:
      The pancreas is rarely involved with metastatic disease, but when it is involved
      the most common tumor is renal cell carcinoma followed by melanoma and non-small
      cell lung cancer. Clinical history and awareness of the primary pancreatic
      mimickers are necessary for arriving at the correct diagnosis. As conventional
      pancreatic adenocarcinoma is uncommon in children and young adults, history of
      other tumors - even ones that usually follow an indolent course - is essential.

PMID- 24021903
TI  - Burkitt's lymphoma treatment in a rural hospital in Sierra Leone.
AB  - BACKGROUND: Sierra Leone is a low-income sub-Saharan country in the endemic
      Burkitt's lymphoma (BL) belt. We performed a prospective trial of a reduced
      intensity chemotherapy protocol for the treatment of paediatric BL. PATIENTS AND
      METHODS: The trial included all children clinically diagnosed with BL between
      2005 and 2008. Biopsy, bone-marrow aspiration, analysis of cerebrospinal fluid,
      abdominal ultrasound and plain x-ray of involved sites were performed when
      feasible. The treatment protocol was a first i.v. dose of cyclophosphamide (CPM)
      40 mg/kg, followed by oral CPM weekly for two doses and then bimonthly to a total
      of six doses. Treatment was based on clinical diagnosis as it was several weeks
      before pathology results were available. RESULTS: Eighty-seven patients were
      included, with a median age 7 years and 4 months; 59/87 (67.8%) were boys. Nearly
      half (n = 17, 42.5%), presented with moderate or severe malnutrition. Biopsy was
      performed in 44 patients, BL being verified in 36 (41.4% of all patients). Most
      children presented with advanced disease: 28 (32%) at stage II, 47 (54%) at stage
      III and 12 (13.8%) at stage IV. Most patients (71/87, 82%) initially responded to
      treatment, but just over half (47/87, 54%) experienced relapse and refractory
      disease. Forty patients (46%) in complete or partial clinical response were lost
      to follow-up. CONCLUSION: The outcome for BL in rural Sierra Leone according to
      this protocol is poor. Low-dose CPM was ineffective. Constraints on performing
      complete diagnosis and staging, frequency of advanced disease at presentation and
      a high drop-out rate might explain our poor results.

PMID- 24021905
TI  - Pharmacokinetic/pharmacodynamic assessment of the effects of parenteral
      administration of a fluoroquinolone on the intestinal microbiota: comparison of
      bactericidal activity at the gut versus the systemic level in a pig model.
AB  - Classical pharmacokinetic/pharmacodynamic studies of antimicrobial agents
      performed by combining plasma concentrations and minimum inhibitory
      concentrations (MICs) are often predictive of the activity of a drug against
      targeted pathogens located at infectious sites closely connected to circulating
      blood. However, these studies do not predict the impact of parenteral
      antimicrobial treatment on intestinal bacteria, which could be responsible for
      transmission of resistance between species or in the environment. The aim of this
      study was to assess the differential antibacterial activity of a fluoroquinolone
      against lung and gut bacteria. Plasma and intestinal concentrations of
      marbofloxacin were assessed in pigs following intramuscular administration, and
      the in vitro relationship between marbofloxacin concentrations and mean bacterial
      inoculum growth in standard broth and in sterilised intestinal contents was
      modelled. It was shown that the increased intestinal exposure to marbofloxacin
      compared with plasma in pigs was compensated by reduced marbofloxacin activity
      against Escherichia coli in the contents of the digestive tract compared with in
      broth. These results showed that marbofloxacin doses used to target pathogens at
      the lung level would similarly affect the bacterial population of the same size
      and with a similar MIC located in the small intestine. However, it was shown that
      the bactericidal activity of marbofloxacin was increased 4- to 7-fold with low
      (10(5)CFU/mL) compared with high (10(8)CFU/mL) inoculum sizes. This result
      suggests that much lower marbofloxacin doses than those classically used would
      potentially eradicate low pulmonary pathogenic inocula while having a minimal
      impact on the large gut microbiota. 

PMID- 24021906
TI  - Mapping the Gastrointestinal Quality of Life Index to short-form 6D utility
      scores.
AB  - PURPOSE: The Gastrointestinal Quality of Life Index (GIQLI) is a disease-specific
      quality of life instrument that is commonly used in gastrointestinal disorders.
      However, no preference weights, which are used to calculate quality-adjusted life
      years for cost-effectiveness analyses, for this instrument have been assigned.
      Therefore, the objective of this study was to develop a mapping function to
      derive utility scores for the GIQLI. METHODS: Patients undergoing elective
      laparoscopic cholecystectomy completed the short-form 6D (SF-6D), a preference
      weighted utility measure, and the GIQLI at baseline and at 1 wk and 1 mo
      postoperatively. The responsiveness of the SF-6D to expected postoperative
      changes as well as the correlation between the SF-6D and the GIQLI was
      investigated. Ordinary least squares regression was performed to derive a mapping
      function using the baseline values, which was then validated using postoperative
      values. Adjusted r(2), mean absolute error, and root mean square error was used
      to determine model performance. RESULTS: A total of 50 patients were included in
      the study (mean age 51.1 [standard deviation 16.8], 28% male). The SF-6D and
      GIQLI domains were responsive to expected postoperative changes, and there was
      high correlation between the SF-6D and four of the five GIQLI domains (excluding
      treatment effects). The final mapping function explained 63% of the variance in
      the derivation sample but had relatively high mean absolute error (0.075 and
      0.067 in the 1-wk and 1-mo samples, respectively) and adjusted root mean square
      error (13.1% and 12.0% in the 1-wk and 1-mo samples, respectively). CONCLUSIONS:
      The GIQLI can be accurately mapped to SF-6D preference weights at the group level
      but may be too inexact at the individual level.

PMID- 24021907
TI  - Approach to diagnosis and treatment of hypercalcemia in a patient with
      malignancy.
AB  - Hypercalcemia is a common complication of malignancy and portends a worse
      prognosis. It causes a variety of symptoms in patients, which can range from
      confusion and polyuria to coma and death. There are 4 broad mechanistic
      categories to classify hypercalcemia of malignancy: local osteolysis secondary to
      metastatic cancer or multiple myeloma, excess parathyroid-related hormone, excess
      1,25-dihydroxyvitamin D production, and ectopic parathyroid hormone production.
      Volume expansion with normal saline solution and treatment with intravenous
      bisphosphonates to decrease osteoclast-mediated bone destruction are effective
      initial therapies. Calcitonin, gallium nitrate, and corticosteroids can serve as
      adjunctive therapies. Denosumab is an attractive therapeutic option for
      refractory cases of hypercalcemia, although more data are required before this
      therapy can be recommended. 

PMID- 24021908
TI  - Insights from the use in clinical practice of eculizumab in adult patients with
      atypical hemolytic uremic syndrome affecting the native kidneys: an analysis of
      19 cases.
AB  - BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a devastating form of
      renal thrombotic microangiopathy. Despite plasma exchange, the standard treatment
      of aHUS for decades, the renal prognosis for patients with aHUS has remained
      poor. We assessed the off-trial use of eculizumab in adult patients with aHUS
      affecting the native kidneys. STUDY DESIGN: A retrospective study was conducted.
      aHUS was defined as the presence of 3 or more of the following: acute kidney
      injury (serum creatinine >1.4 mg/dL [120 MUmol/L]), mechanical hemolytic anemia,
      thrombocytopenia, and the presence of thrombotic microangiopathy features in a
      kidney biopsy specimen. Patients who had received 4 or more weekly 900-mg
      infusions of eculizumab were included. SETTING & PARTICIPANTS: 19 patients were
      identified through a query sent to all French nephrology centers. OUTCOMES &
      MEASUREMENTS: Evolution of kidney function, hemolysis, and thrombocytopenia after
      the initiation of eculizumab therapy. RESULTS: All patients had acute kidney
      injury (serum creatinine range, 2.2-17.0 mg/dL) and 12 required hemodialysis.
      Thirteen patients carried a mutation in 1 complement gene and 1 had anti-factor H
      antibodies. For first-line therapy, 16 patients underwent plasma exchange and 3
      patients received eculizumab. Median time between aHUS onset and eculizumab
      therapy initiation was 6 (range, 1-60) days and median time to platelet count
      normalization after eculizumab therapy initiation was 6 (range, 2-42) days. At
      the 3-month follow-up, 4 patients still required dialysis, 8 had non-dialysis
      dependent chronic kidney disease, and 7 had normalized kidney function. At last
      follow-up (range, 4-22 months), 3 patients remained dialysis dependent, 7 had non
      dialysis-dependent chronic kidney disease (estimated glomerular filtration rate,
      17-55 mL/min/1.73 m(2)), and 9 had normal kidney function. Risks of reaching end
      stage renal disease within 3 months and 1 year of aHUS onset were reduced by half
      in eculizumab-treated patients compared with recent historical controls.
      LIMITATIONS: Retrospective study and use of historical controls. CONCLUSIONS: Our
      data indicate that eculizumab improves kidney disease outcome in patients with
      aHUS.

PMID- 24021909
TI  - Anti-phospholipase A2 receptor antibodies and malignancy in membranous
      nephropathy.

PMID- 24021910
TI  - Sensitivity of myoma imaging using laparoscopic ultrasound compared with magnetic
      resonance imaging and transvaginal ultrasound.
AB  - STUDY OBJECTIVE: To determine the efficacy of laparoscopic ultrasound (LUS) as
      compared with contrast-enhanced magnetic resonance imaging (CE-MRI) and
      transvaginal ultrasound (TVUS) in detection of uterine myomas. DESIGN:
      Retrospective study of imaging methods used in a trial of LUS-guided
      radiofrequency volumetric thermal ablation in women with symptomatic myomas
      (Canadian Task Force classification II-2). SETTING: Eleven medical university or
      private outpatient surgery clinics in the United States (nine sites) and Latin
      America (two sites). PATIENTS: One hundred thirty-five women with symptomatic
      myomas and objectively confirmed moderate to severe heavy menstrual bleeding.
      INTERVENTIONS: LUS-guided radiofrequency volumetric thermal ablation of myomas.
      MEASUREMENTS AND MAIN RESULTS: Preoperative TVUS scans and CE-MRIs were read at
      each site, and all CE-MRIs were read by a central reader. LUS-guided scans were
      obtained intraoperatively by each surgeon by mapping the uterus just before
      radiofrequency volumetric thermal ablation. The imaging methods and their yields
      in terms of number of myomas found per subject were as follows: TVUS, 403 myomas
      (mean [SD] 3 [1.8]; range, 1-8); site CE-MRI, 562 myomas (4.2 [3.8]; range, 1
      18); central reader, 619 myomas (4.6 [3.7]; range, 0-20); and LUS, 818 myomas
      (6.1 [4.9]; range, 1-29) (p < .001). LUS was superior to TVUS, CE-MRI, and the
      central reader for detection of small (<=1 cm(3)) myomas. Most imaged myomas were
      intramural: 197 (50.9%) by TVUS, 298 (55.5%) by site CE-MRI, 290 (48.7%) by the
      central reader, and 386 (48.5%) by LUS. CONCLUSION: Compared with CE-MRI and
      TVUS, LUS demonstrates the most myomas, regardless of size or type.

PMID- 24021911
TI  - Vasotocinergic and isotocinergic systems in the gilthead sea bream (Sparus
      aurata): an osmoregulatory story.
AB  - To investigate the physiological roles of arginine vasotocin (AVT) and isotocin
      (IT) in osmoregulatory process in gilthead sea bream (Sparus aurata), a time
      course study (0, 12h, and 1, 3, 7 and 14 days) has been performed in specimens
      submitted to hypoosmotic (from 400/00 salinity to 50/00 salinity) or hyperosmotic
      (from 400/00 salinity to 550/00 salinity) challenges. Plasma and liver
      osmoregulatory and metabolic parameters, as well as AVT and IT pituitary contents
      were determined concomitantly with hypothalamic pro-vasotocin (pro-VT) and pro
      isotocin (pro-IT) mRNA expression levels. Previously, sequences coding for pro-VT
      and pro-IT cDNAs were cloned. Two osmoregulatory periods related to plasma
      osmolality and metabolic parameter variations could be distinguished: i) an
      adaptative period, from 12h to 3 days after transfer, and ii) a chronic
      regulatory period, starting at day 3 after transfer. Higher values in
      hypothalamic pro-VT and pro-IT mRNA expression as well as in pituitary AVT and IT
      storage levels in both hypo- and/or hyper-osmotic transfers have been
      distinguished. These increase correlated with changes in plasma cortisol levels,
      suggesting an interaction between this hormone and pro-VT expression.
      Furthermore, pro-IT expression enhancement also suggests a role of the
      isotocinergic system as a modulator in the acute stress response induced by hyper
      osmotic challenge in S. aurata.

PMID- 24021912
TI  - Metabolic depression during warm torpor in the Golden spiny mouse (Acomys
      russatus) does not affect mitochondrial respiration and hydrogen peroxide
      release.
AB  - Small mammals actively decrease metabolism during daily torpor and hibernation to
      save energy. Recently, depression of mitochondrial substrate oxidation in
      isolated liver mitochondria was observed and associated to
      hypothermic/hypometabolic states in Djungarian hamsters, mice and hibernators. We
      aimed to clarify whether hypothermia or hypometabolism causes mitochondrial
      depression during torpor by studying the Golden spiny mouse (Acomys russatus), a
      desert rodent which performs daily torpor at high ambient temperatures of 32
      degrees C. Notably, metabolic rate but not body temperature is significantly
      decreased under these conditions. In isolated liver, heart, skeletal muscle or
      kidney mitochondria we found no depression of respiration. Moderate cold exposure
      lowered torpor body temperature but had minor effects on minimal metabolic rate
      in torpor. Neither decreased body temperature nor metabolic rate impacted
      mitochondrial respiration. Measurements of mitochondrial proton leak kinetics and
      determination of P/O ratio revealed no differences in mitochondrial efficiency.
      Hydrogen peroxide release from mitochondria was not affected. We conclude that
      interspecies differences of mitochondrial depression during torpor do not support
      a general relationship between mitochondrial respiration, body temperature and
      metabolic rate. In Golden spiny mice, reduction of metabolic rate at mild
      temperatures is not triggered by depression of substrate oxidation as found in
      liver mitochondria from other cold-exposed rodents. 

PMID- 24021913
TI  - Commentary: Foetal growth, preterm birth and childhood undernutrition.

PMID- 24021914
TI  - Evaluation of amrubicin as a third or later line of chemotherapy for advanced non
      small cell lung cancer.
AB  - BACKGROUND: Currently, there are no standard cytotoxic treatments for non-small
      cell lung cancer (NSCLC) patients beyond third-line therapy. The purpose of this
      study was to evaluate the efficacy of amrubicin monotherapy as a salvage
      treatment in heavily pretreated NSCLC patients. METHODS: The records of NSCLC
      patients who received amrubicin monotherapy as a third or later line of
      chemotherapy at a Kitasato University Hospital between January 2009 and December
      2012 were retrospectively reviewed. Amrubicin was administered to patients by
      intravenous injection at a dose of 35 or 40 mg/m(2) daily on 3 consecutive days,
      and cycles were repeated at 3-week intervals. RESULTS: There were 36 patients who
      met the inclusion criteria. Their median number of prior chemotherapy treatments
      was 4 (range 2-7), and the median number of chemotherapy cycles per patient was 4
      (range 1-9). Grade 3 or 4 hematologic toxicities included neutropenia (61.1%),
      leukopenia (58.3%), thrombocytopenia (22.2%) and anemia (11.1%). Febrile
      neutropenia occurred in 8 patients (22.2%). Nonhematologic toxicities were mild.
      The overall response rate, median progression-free survival time and median
      survival time were 8.3%, 1.7 months, and 6.3 months, respectively. Progression
      free survival time was the same, i.e. 1.7 months in both groups i.e. the 35- and
      the 40-mg/m(2)-dose groups. CONCLUSION: Amrubicin exhibits modest activity and
      acceptable toxicity when used as a third or later line of chemotherapy for
      advanced NSCLC.

PMID- 24021915
TI  - The Affordable Care Act and the opportunity to improve prevention in women: how
      to make the most of the law.

PMID- 24021916
TI  - Acetylcholine mediates AMPK-dependent autophagic cytoprotection in H9c2 cells
      during hypoxia/reoxygenation injury.
AB  - BACKGROUND: Acetylcholine (ACh), a neurotransmitter of vagal nerve, offers
      tolerance to ischemia/reperfusion injury. Given the regulation of autophagy in
      cardioprotection, this study was to examine the role of autophagy in ACh-elicited
      protection against hypoxia/reoxygenation (HR) injury. METHODS: H9c2 cells were
      subjected to HR injury. Autophagy was determined by transmission electron
      microscopy, MDC staining and western blot. MTT kit, LDH and CK release, ATP
      content and TUNEL assay were used to evaluate cardiomyocytes injury. Atg7 and
      AMPK knockdown was performed with siRNA transfection. RESULTS: Following 4, 8, 12
      and 16 h reoxygenation, autophagosomes were decreased along with reduced cell
      viability. ACh during 4 h reoxygenation facilitated autophagy as evidence by
      increased autophagosomes and MDC labeling autophagic vacuoles. H9c2 cells treated
      with ACh also underwent a biochemical changes by increased ratio of LC3-II/LC3-I
      and autophagy flux (decreased p62), while muscarinic receptor antagonist atropine
      suppressed these effects. Induction of autophagy was correlated with enhanced
      cell survival and decreased apoptosis. Autophagy inhibition with chloroquine and
      Atg7 siRNA significantly attenuated ACh-induced cytoprotection. ACh-elicited
      autophagy activation could be related to increased AMPK phosphorylation and
      decreased mTOR phosphorylation. AMPK siRNA exhibited an elevation in mTOR
      phosphorylation and reduced the ratio of LC3-II/LC3-I. Importantly, AMPK
      knockdown desensitized H9c2 cells to ACh-mediated protection. CONCLUSIONS: These
      data provided first evidence that ACh-induced autophagy elicited cytoprotective
      effects through muscarinic receptor activated-AMPK-mTOR pathway, and suggested a
      novel mechanism of ACh-induced tolerance against HR injury.

PMID- 24021917
TI  - Investigation of chronic diarrhoea in infancy.
AB  - Diarrhoea in infants and young children is defined as >200g/day of stools, and
      occurs when there is an imbalance between intestinal fluids absorption and
      secretion. This may be caused by either a decreased absorption (osmotic
      diarrhoea) or an increased secretion (secretory diarrhoea). Chronic diarrhoea
      defines intestinal loss of water and electrolytes with increased stool frequency,
      reduced consistency and larger volume over more than 14days. This disorder in
      children shows a wide range of aetiologies depending on the age. The knowledge of
      common and rare aetiologies is important to optimize the diagnostic approach. A
      stepwise approach, starting with a comprehensive history, physical examination,
      inspection and collection of stool samples, helps to devise appropriate
      diagnostic and therapeutic management. In this article we discuss the
      pathophysiology, aetiology and possible approach to chronic diarrhoea in infancy.

PMID- 24021918
TI  - Airway ventilation pressures during bronchoscopy, bronchial blocker, and double
      lumen endotracheal tube use: an in vitro study.
AB  - OBJECTIVE: To quantify inspiratory flow resistance of instrumented single-lumen
      and double-lumen endotracheal tubes. DESIGN: Bench-top in vitro experiments.
      SETTING: Laboratory of a university hospital. PARTICIPANTS: In vitro lung
      simulator. INTERVENTIONS: A lung simulator was ventilated mechanically via
      several single- and double-lumen endotracheal tubes (ETT) that were instrumented
      with adult and pediatric bronchoscopes as well as bronchial blockers. While
      ventilating with a square-flow wave and increasing peak inspiratory flow from 10
      100 L/min, the pressures proximal and distal to the instrumented ETT were
      measured. Flow (Q) and the pressure loss (?P) were related with regression of the
      quadratic equation: ?P=k1Q+k2Q2. MEASUREMENTS AND MAIN RESULTS: With all
      combinations of single-lumen endotracheal tubes, double-lumen endotracheal tubes,
      bronchial blockers, and adult and pediatric bronchoscopes, ?P was accurately
      related to Q using the quadratic equation with excellent fit, R2>0.99 for all
      combinations. The regression parameters k1 and k2 were statistically significant
      for all combinations except k1 with a bronchoscope through 37-Fr double-lumen
      endotracheal tube. Parameter k2 was dominant at flows above 10 L/min for
      uninstrumented airways and 20 L/min for instrumented airways. ?P increased
      dramatically with flow, and increased with decreasing endotracheal tube size or
      addition of instrumentation in a quantitatively predictable manner. CONCLUSIONS:
      Pressure loss across instrumented endotracheal tubes follows a predictable flow
      dependant quadratic pattern. Using the quantitative in vitro results of this
      study, a clinician can maximize inspiratory ventilation pressures during these
      situations without delivering excessive airway pressures to the patient.

PMID- 24021920
TI  - Head movements suggest canal and otolith projections are activated during
      galvanic vestibular stimulation.
AB  - Three-dimensional changes in the angular orientation of the head were monitored
      during galvanic vestibular stimulation (GVS) delivered through electrodes
      implanted bilaterally in the tensor tympani muscle of the guinea-pig middle ear.
      Bilateral GVS was delivered by passing current between both ears with the anode
      situated in one ear and the cathode in the other ear. Unilateral GVS was also
      delivered between one ear and an indifferent electrode on the skull. Constant
      current stimulation caused the head to tilt predominantly within the roll and yaw
      planes toward an ear stimulated with anodal current and away from an ear
      stimulated with cathodal current. No significant head tilt in the pitch plane was
      observed with either bilateral or unilateral GVS. Bilateral GVS was found to
      induce significantly greater roll head tilt (RHT) and yaw head tilt (YHT) than
      the same intensity of unilateral anodal or cathodal GVS, but not the sum of
      responses induced by the two polarities of unilateral GVS. Significant
      asymmetries were observed in the responses of YHT and RHT for unilateral anodal
      and cathodal GVS; unilateral cathodal stimulation generated greater head
      deviation compared with the same intensity of unilateral anodal stimulation.
      These asymmetric responses are consistent with activation of irregularly
      discharging afferents, which have been shown previously to exhibit asymmetric
      responses for anodal and cathodal GVS (Kim and Curthoys, 2004). Together with the
      observations of previous guinea-pig studies, the results suggest that head
      movements induced by GVS may be mediated by irregularly discharging afferents
      innervating the otoliths, and possibly the horizontal semicircular canals. 

PMID- 24021919
TI  - Inner ear insult ablates the arousal response to hypoxia and hypercarbia.
AB  - INTRODUCTION: Sudden Infant Death Syndrome (SIDS) remains the leading cause of
      infant mortality in Western societies. A prior study identified an association
      between hearing suppression on the newborn hearing test and subsequent death from
      SIDS. This is the first finding of an abnormality in SIDS cases prior to death. A
      following study identified that inner ear dysfunction precipitates a marked
      suppression of the hypercapnic ventilatory response (HCVR). Failure of arousal
      has been proposed to be a key component in SIDS. The objective of the present
      study was to assess whether inner ear dysfunction not only weakens the
      hypercapnic response, but also plays a role in suppressing the arousal response
      to suffocating gas mixtures. METHODS: Wild-type mice (n=28) received intra
      tympanic gentamicin (IT-Gent) injections bilaterally or unilaterally to
      precipitate inner ear hair cell dysfunction. Three control groups (n=22) received
      intra-tympanic saline (IT-Saline) bilaterally or unilaterally (right or left), or
      intra-peritoneal gentamicin (IP-Gent). The body movement arousal responses to
      severe hypoxia-hypercarbia combined (5% CO2 in nitrogen) were tested under light
      anesthesia 8 days following the administration of gentamicin or saline. RESULTS:
      After injections, the bilateral and unilateral IT-Gent-treated animals behaved
      similarly to controls, however the HCVR as well as the arousal movements in
      response to severe hypoxia-hypercarbia were suppressed in IT-Gent-treated animals
      compared to control animals (P<0.05). Thus the HCVR was significantly decreased
      in the bilateral (n=9) and unilateral IT-Gent-treated mice (n=19) compared to
      bilateral (n=7) and unilateral IT-Saline (n=9) control groups (p<0.05). Arousal
      movements were suppressed in the bilateral IT-Gent group (n=9) compared to
      bilateral IT-Saline controls (n=7, P<0.0001) and in the unilateral IT-Gent group
      (n=19) compared to unilateral IT-Saline controls (n=10, P<0.0001). DISCUSSION:
      The findings support the theory that inner ear dysfunction could be relevant in
      the pathophysiology of SIDS. The inner ear appears to play a key role in arousal
      from suffocating gas mixtures that has not been previously identified.

PMID- 24021921
TI  - Spatial accessibility in suboptimally configured health care systems: a modified
      two-step floating catchment area (M2SFCA) metric.
AB  - The floating catchment area (FCA) family of metrics employ principles from
      gravity-based models to incorporate supply, demand, and distance in their
      characterization of the spatial accessibility of health care resources. Unlike
      traditional gravity models, the FCA metrics provide an output in highly
      interpretable container-like units (e.g., physicians per person). This work
      explores two significant issues related to FCA metrics. First, the Three Step
      Floating Catchment Area is critically examined. Next, the research shows that all
      FCA metrics contain an underlying assumption that supply locations are optimally
      configured to meet the needs of the population within the system. Because truly
      optimal configurations are highly unlikely in real-world health care systems, a
      modified two-step floating catchment area (M2SFCA) metric is offered to address
      this issue. The M2SFCA is built upon previous FCA metrics, but allows for spatial
      accessibility to be discounted as a result of the suboptimal configuration of
      health care facilities within the system. The utility of the new metric is
      demonstrated through simulated data examples and a case study exploring acute
      care hospitals in Michigan. 

PMID- 24021922
TI  - The behavioral satiety sequence in pigeons (Columba livia). Description and
      development of a method for quantitative analysis.
AB  - The postprandial event known as the specific dynamic action is an evolutionarily
      conserved physiological set of metabolic responses to feeding. Its behavioral
      counterpart, a sequence of drinking, maintenance (e.g., grooming) and sleep-like
      behaviors known as the behavioral satiety sequence (BSS), has been thoroughly
      described in rodents and has enabled the refined evaluation of potential appetite
      modifiers. However, the presence and attributes of a BSS have not been
      systematically studied in non-mammalian species. Here, we describe the BSS
      induced in pigeons (Columba livia) by 1) the presentation of a palatable seed
      mixture (SM) food to free-feeding animals (SM+FF condition) and 2) re-feeding
      after a 24-h fasting period (FD24h+SM), which was examined by continuous
      behavioral recording for 2h. We then compare these patterns to those observed in
      free-feeding (FF) animals. A set of graphic representations and indexes, drawn
      from these behaviors (latency, time-to-peak, inter-peak intervals and the first
      intersection between feeding curves and those of other BSS-typical behaviors)
      were used to describe the temporal structure and sequential relationships between
      the pigeon's BSS components. Cramer-von Mises-based statistical procedures and
      bootstrapping-based methods to compare pairs of complex behavioral curves were
      described and used for comparisons among the behavioral profiles during the free
      feeding recordings and after fasting- and SM-induced BSS. FD24h+SM- and SM+FF
      induced feeding were consistently followed by a similar sequence of increased
      bouts of drinking, followed by preening and then sleep, which were significantly
      different from that of FF birds. The sequential and temporal patterns of the
      pigeon's BSS were not affected by differences in food intake or by dissimilarity
      in motivational content of feeding stimuli. The present data indicated that a BSS
      pattern can be reliably evoked in the pigeon, in a chronological succession and
      sequence that strongly resembled that observed in rodents and primates. This
      pattern can be quantitatively described and compared using different suitable and
      coordinated behavioral measures, enabling further studies on the comparative and
      evolutionary aspects of the mechanisms that shape the post-consummatory
      behavioral flux in amniotes. 

PMID- 24021923
TI  - Relationship between stage II transport and number of chewing strokes as
      mastication progresses.
AB  - As mastication progresses, little is known about the occurrence of the stage II
      transport (oro-pharyngeal bolus transport). This study aimed to investigate the
      relationship between stage II transport and bolus aggregation in the pharynx and
      the number of chewing strokes. Twenty-five clinical residents with natural
      dentitions were recruited. The subjects were asked to chew gummy jelly with their
      preferred rhythm and to swallow the bolus at their preferred timing. To
      investigate stage II transport and bolus aggregation in the pharynx, a transnasal
      endoscope was used. The number of chewing strokes was measured by
      electromyographic activity from the masseter muscle. The mean numbers of chewing
      strokes of pre-stage II transport and post-stage II transport were 29.8 and 8.1,
      respectively; the difference was significant (p<0.01). The ratio of the number of
      chewing strokes of pre-stage II transport to that of post-stage II transport was
      4.0 to 1.0. This study showed that stage II transport started at four-fifths of
      the way along the progress of mastication, and that stage II transport and bolus
      aggregation in the pharynx are related to the number of chewing strokes. 

PMID- 24021924
TI  - Are cats (Felis catus) from multi-cat households more stressed? Evidence from
      assessment of fecal glucocorticoid metabolite analysis.
AB  - Given the social and territorial features described in feral cats, it is commonly
      assumed that life in multi-cat households is stressful for domestic cats and
      suggested that cats kept as single pets are likely to have better welfare. On the
      other hand, it has been hypothesized that under high densities cats can organize
      themselves socially thus preventing stress when spatial dispersion is
      unavailable. This study was aimed at comparing the general arousal underpinning
      emotional distress in single housed cats and in cats from multi-cat households (2
      and 3-4 cats) on the basis of fecal glucocorticoid metabolites (GCM) measured via
      enzyme immunoassay (EIA). GCM did not significantly vary as a function of living
      style (single, double or group-housing); highly stressed individuals were equally
      likely in the three groups. Young cats in multi-cat households had lower GCM, and
      overall cats that tolerate (as opposed to dislike) petting by the owners tended
      to have higher GCM levels. Other environmental aspects within cat houses (e.g.
      relationship with humans, resource availability) may play a more important role
      in day to day feline arousal levels than the number of cats per se. 

PMID- 24021925
TI  - Lactational exposure to sulpiride: assessment of maternal care and reproductive
      and behavioral parameters of male rat pups.
AB  - Dopaminergic receptor antagonists may be used as galactagogues because they
      increase serum prolactin (PRL) by counteracting the inhibitory influence of
      dopamine on PRL secretion. The antipsychotic drug sulpiride (SUL) is documented
      to be effective as a galactagogue, but it is transferred through milk to the
      neonates. The aim of the present study was to evaluate if maternal exposure to
      SUL during lactation could disrupt maternal care and/or male offspring
      reproductive development. The dams were treated daily (gavage) with SUL 2.5mg/kg
      or 25mg/kg during lactation. Maternal behavior was analyzed on lactational days 5
      and 10. In offspring, reproductive and behavioral parameters were analyzed at
      different time points. SUL treatment did not impair maternal care, but caused
      testicular damage in male offspring. At postnatal day 90, a reduction in testis
      weight, volume of seminiferous tubule and histopathological alterations such as
      an increased percentage of abnormal seminiferous tubules were observed. Data
      shows that maternal exposure to SUL during lactation may impact the reproductive
      development of male rats and the testes seem to be the main target organ at
      adulthood. 

PMID- 24021926
TI  - Behavioural and immunological responses to an immune challenge in Octopus
      vulgaris.
AB  - Behavioural and immunological changes consequent to stress and infection are
      largely unexplored in cephalopods, despite the wide employment of species such as
      Octopus vulgaris in studies that require their manipulation and prolonged
      maintenance in captivity. Here we explore O. vulgaris behavioural and
      immunological (i.e. haemocyte number and serum lysozyme activity) responses to an
      in vivo immune challenge with Escherichia coli lipopolysaccharides (LPS).
      Behavioural changes of immune-treated and sham-injected animals were observed in
      both sight-allowed and isolated conditions, i.e. visually interacting or not with
      a conspecific. Immune stimulation primarily caused a significant increase in the
      number of circulating haemocytes 4h after the treatment, while serum lysozyme
      activity showed a less clear response. However, the effect of LPS on the
      circulating haemocytes begins to vanish 24h after injection. Our observations
      indicate a significant change in behaviour consequent to LPS administration, with
      treated octopuses exhibiting a decrease of general activity pattern when kept in
      the isolated condition. A similar decrease was not observed in the sight-allowed
      condition, where we noticed a specific significant reduction only in the time
      spent to visually interact with the conspecific. Overall, significant, but lower,
      behavioural and immunological effects of injection were detected also in sham
      injected animals, suggesting a non-trivial susceptibility to manipulation and
      haemolymph sampling. Our results gain importance in light of changes of the
      regulations for the use of cephalopods in scientific procedures that call for the
      prompt development of guidelines, covering many aspects of cephalopod provision,
      maintenance and welfare. 

PMID- 24021927
TI  - Quantification of ventilation distribution in regional lung injury by electrical
      impedance tomography and xenon computed tomography.
AB  - Validation studies of electrical impedance tomography (EIT) based assessment of
      regional ventilation under pathological conditions are required to prove that EIT
      can reliably quantify heterogeneous ventilation distribution with sufficient
      accuracy. The objective of our study was to validate EIT measurements of regional
      ventilation through a comparison with xenon-multidetector-row computed tomography
      (XeCT) in an animal model of sub-lobar lung injury. Nine anesthetized
      mechanically ventilated supine pigs were examined before and after the induction
      of lung injury in two adjacent sub-lobar segments of the right lung by saline
      lavage or endotoxin instillation. Regional ventilation was determined in 32
      anteroposterior regions of interest in the right and left lungs and the
      ventilation change quantified by difference images between injury and control.
      Six animals were included in the final analysis. Measurements of regional
      ventilation by EIT and XeCT correlated well before (rs = 0.89 right, rs = 0.90
      left lung) and after local injury (rs = 0.79 and 0.92, respectively). No bias and
      narrow limits of agreement were found during both conditions. The ventilation
      decrease in the right injured lung was correspondingly measured by both
      modalities (5.5%+/-1.1% by EIT and 5.4%+/-1.9% by XeCT, p = 0.94). EIT was
      inferior to clearly separate the exact anatomical location of the regional
      injuries. Regional ventilation was overestimated (<2%) in the most ventral and
      dorsal regions and underestimated (2%) in the middle regions by EIT compared to
      XeCT. This study shows that EIT is able to reliably discern even small
      ventilation changes on sub-lobar level. 

PMID- 24021928
TI  - Role of particle size and composition in metal adsorption by solids deposited on
      urban road surfaces.
AB  - Despite common knowledge that the metal content adsorbed by fine particles is
      relatively higher compared to coarser particles, the reasons for this phenomenon
      have gained little research attention. The research study discussed in the paper
      investigated the variations in metal content for different particle sizes of
      solids associated with pollutant build-up on urban road surfaces. Data analysis
      confirmed that parameters favourable for metal adsorption to solids such as
      specific surface area, organic carbon content, effective cation exchange capacity
      and clay forming minerals content decrease with the increase in particle size.
      Furthermore, the mineralogical composition of solids was found to be the
      governing factor influencing the specific surface area and effective cation
      exchange capacity. There is high quartz content in particles >150 MUm compared to
      particles <150 MUm. As particle size reduces below 150 MUm, the clay forming
      minerals content increases, providing favourable physical and chemical properties
      that influence adsorption. 

PMID- 24021929
TI  - Desirability and expectations of the UK MS Register: views of people with MS.
AB  - BACKGROUND: Internet-based health registers are increasingly commonly used for
      health promotion and medical research, yet little is known about what the patient
      groups who help form the basis of such registers expect from these tools.
      Mismatches between patient expectations and the register design may limit the
      long-term utility of such registers. OBJECTIVE: This study elicited the views of
      people with Multiple Sclerosis (PwMS) on the desirability and expectations
      regarding a UK Register for MS. METHODS: Participants were recruited through a
      range of traditional means (newsletters, adverts, word of mouth), as well as via
      the Internet, to obtain a broad sample of PwMS. Semi-structured interviews were
      conducted over the telephone, and the questions asked about: the desirability of
      the Register; what the participants envisaged the Register actually being used
      for; and what they hoped the Register could be used for. RESULTS: The majority of
      individuals' points postulated that a UK MS Register would be useful, but a range
      of potential concerns were identified by the sample, such as security,
      accessibility for all PwMS, and the validity of self-report data. Analysis of the
      responses revealed a difference between what PwMS thought the Register would be
      used for, and how they wanted it to be used, particularly in relation to a
      desired social contact, exchange, and networking function. CONCLUSIONS: The
      security and accessibility of the website, the validity of the data, and
      mismatches between the expected and actual uses, are all issues of importance in
      the development of e-health tools, if PwMS are to be successfully engaged over
      time.

PMID- 24021930
TI  - Expression of LEF1 is an independent prognostic factor for patients with oral
      squamous cell carcinoma.
AB  - BACKGROUND/PURPOSE: Lymphoid-enhancing factor 1 (LEF1) is a transcription factor
      mediating Wnt/beta-catenin signaling. In this study, we analyzed the
      clinicopathologic significance of LEF1 expression in oral squamous cell carcinoma
      (OSCC). METHODS: Expression levels of LEF1 in 135 cases of OSCC were determined
      by immunohistochemistry. The results were correlated with clinicopathologic
      parameters and patient outcome. RESULTS: LEF1 was only occasionally detected in
      basal and parabasal cells of nontumorous squamous epithelium. Overexpression of
      LEF1 was observed in 33 of 135 OSCCs (24%). LEF1 was more frequently expressed in
      moderately to poorly differentiated cancer (p = 0.0035) and was associated with
      lymphovascular invasion (p = 0.0252). Overexpression of LEF1 was significantly
      associated with poor prognosis (p = 0.0176, hazard ratio = 1.96, 95% CI = 1.02
      3.75). Multivariate analysis revealed LEF1expression and margin status to be the
      significant independent predictors for overall survival. CONCLUSION: Our study
      suggests LEF1 expression in OSCC may play an important role in tumor progression
      and can be served as a predictor of poor prognosis for patients with OSCC.

PMID- 24021931
TI  - Obesity - a promoter of allergy?
AB  - The prevalence of both obesity and allergy has been increasing throughout the
      world, leading to the hypothesis that the two are linked to one another. This
      overview summarizes the results of 34 studies from 2002 to 2012 that investigated
      a possible contributing effect of increasing body mass on the development and
      prevalence of various atopic diseases. Obesity was found to clearly affect
      bronchial asthma. However, the correlation was stronger in the nonatopic asthma
      phenotype. Obesity was found to be associated with the development of atopic
      dermatitis in children only. No clear association was found between obesity and
      the prevalence of allergic rhinitis or allergic conjunctivitis or increased
      sensitization to food allergens. This review sums up our study results and
      discusses a possible role of obesity in the promotion of allergy and asthma. 

PMID- 24021932
TI  - Architectural organization of the african elephant diencephalon and brainstem.
AB  - The current study examined the organization of the diencephalon and brainstem of
      the African elephant (Loxodonta africana) - a region of the elephant brain that
      has not been examined for at least 50 years. The current description, employing
      material amenable for use with modern neuroanatomical methods, shows that, for
      the most part, the elephant diencephalon and brainstem are what could be
      considered typically mammalian, with subtle differences in proportions and
      topology. The variations from these previous descriptions, where they occurred,
      were related to four specific aspects of neural information processing: (1) the
      motor systems, (2) the auditory and vocalization systems, (3) the orexinergic
      satiety/wakefulness centre of the hypothalamus and the locus coeruleus, and (4)
      the potential neurogenic lining of the brainstem. For the motor systems, three
      specific structures exhibited interesting differences in organization - the pars
      compacta of the substantia nigra, the facial motor nerve nucleus, and the
      inferior olivary nuclear complex, all related to the timing and learning of
      movements and likely related to the control of the trunk. The dopaminergic
      neurons of the substantia nigra appear to form distinct islands separated from
      each other by large fibre pathways, an appearance unique to the elephant. Each
      island may send topologically organized projections to the striatum forming a
      dopaminergic innervation mosaic that may relate to trunk movements. At least five
      regions of the combined vocalization production and auditory/seismic reception
      system were specialized, including the large and distinct nucleus ellipticus of
      the periaqueductal grey matter, the enlarged lateral superior olivary nucleus,
      the novel transverse infrageniculate nucleus of the dorsal thalamus, the enlarged
      dorsal column nuclei and the ventral posterior inferior nucleus of the dorsal
      thalamus. These specializations, related to production and reception of
      infrasound, allow the proposal of a novel concept regarding the reception and
      localization of infrasonic sources. The orexinergic system of the hypothalamus
      displayed a medial hypothalamic parvocellular cluster of neurons in addition to
      the magnocellular clusters typical of mammals located in the lateral
      hypothalamus, and a novel medial division of the locus coeruleus was observed in
      the pons. These systems are related to appetitive drive and promotion of
      wakefulness, two aspects of elephant behaviour that appear to be inextricably
      linked. Lastly, we observed an extensive potential neurogenic lining of the
      ventricles throughout the brainstem that is present in even quite old elephants,
      although the function of these cells remains elusive. These observations combined
      demonstrate that, while much of the elephant brainstem is typically mammalian,
      certain aspects of the anatomy related to specialized behaviour of elephants are
      present and instructive in understanding elephant behaviour.

PMID- 24021933
TI  - Role of nutritional reserves and body size in Anopheles gambiae males mating
      success.
AB  - A better knowledge of the different parameters that account for male mating
      success in the wild is critical to the development of genetic control strategies.
      In this study, we measured energy budgets (total sugar and glycogen) as the daily
      energetic investment in swarming males of An. gambiae s.s. M and S molecular
      forms from two different field locations, VK7 and Soumousso. We also looked at
      the difference between energetic reserves in mated males compared to unmated
      ones, and assessed wing length in both molecular forms to explore whether this
      phenotypic trait was involved in swarming behavior or mating success. The current
      study showed that the energetic cost of 25 min of swarming was around 50% of the
      male's sugar (M form: 48.5%, S form: 56.2%) and glycogen (M form: 53.1%, S form:
      59%) reserves. However, no difference in carbohydrate content was observed
      between mated and unmated males. Mated males were found to be bigger than unmated
      ones, while intermediate size of males is advantageous in mating system, both in
      M and S molecular forms and when collected in two different locations. Regardless
      of the collection location, no difference in wing size was observed in swarming
      males collected early or late during a particular swarm. The results are
      discussed in the context sexual selection in different ecological locations.

PMID- 24021934
TI  - Physiotherapist-designed aquatic exercise programme for community-dwelling elders
      with osteoarthritis of the knee: a Hong Kong pilot study.
AB  - OBJECTIVES. To examine the effectiveness and feasibility of a community-based
      aquatic exercise programme for elders with osteoarthritis of the knee. DESIGN.
      Prospective intervention study, with a before-and-after design. SETTING.
      Community elders. PARTICIPANTS. Twenty elders aged 65 years or above (mean, 72
      years) attending four Elderly Health Centres of the Department of Health who had
      suffered from osteoarthritis of the knee for at least 3 years and with mild-to
      severe knee pain. INTERVENTION. A 10-week aquatic exercise programme designed and
      led by physiotherapists. MAIN OUTCOME MEASURES. Range of motion and power of
      extension of the knees, functional reach test, repeated sit-to-stand test, and
      the Chinese Arthritis Impact Measurement Scales 2. RESULTS. There was an
      improvement in the median range of knee flexion from 115 degrees  to 125 degrees 
      (P<0.01) and the median strength of the quadriceps from 9 kg to 21 kg (P<0.001).
      The median score of the functional reach test increased from 20 cm to 28 cm
      (P<0.001) and the repeated sit-to-stand test from 10 to 14 repetitions (P<0.001).
      Also, there was an improvement in the mobility level (P<0.01), walking and
      bending ability of the trunk (P<0.05), levels of pain (P<0.01) and mood (P<0.01),
      and the total score (P<0.01) in the Chinese Arthritis Impact Measurement Scales
      2. CONCLUSIONS. Physiotherapist-designed aquatic exercise has definite benefits
      in terms of physical and psychosocial functioning, and should be promoted as one
      of the strategies to enhance long-term self-management of community elders with
      knee osteoarthritis. 

PMID- 24021935
TI  - Elective unilateral total knee replacement using continuous femoral nerve
      blockade versus conventional patient-controlled analgesia: perioperative patient
      management based on a multidisciplinary pathway.
AB  - OBJECTIVES. To evaluate the effectiveness of our new multidisciplinary pathway
      for total knee replacement patients and compare outcomes after continuous femoral
      nerve blockade versus conventional patient-controlled analgesia for postoperative
      pain. DESIGN. Randomised controlled trial in a routine clinical setting. SETTING.
      Acute orthopaedic wards and operating theatres, Yan Chai Hospital, Hong Kong.
      PATIENTS. Sixty patients underwent elective unilateral total knee replacement
      under spinal anaesthesia from May 2009 to September 2011 and were randomly
      assigned to continuous femoral nerve blockade or conventional patient-controlled
      analgesia (30 patients in each group). MAIN OUTCOME MEASURES. Quality of pain
      control was evaluated by pain scores at rest and during mobilisation, opioid
      consumption, frequency of side-effects, and patient satisfaction score.
      Rehabilitation progress was assessed according to the day of first starting
      weight-bearing exercise, day of independent walking in the ward with aid, Timed
      Up and Go test, and time elapsing till discharge. Surgical outcome was assessed
      by the Knee Society score 6 months after discharge, re-admissions, and occurrence
      of complications. RESULTS. Patients having continuous femoral nerve blockade
      tended to have less pain on movement and achieved earlier mobilisation than those
      having patient-controlled analgesia. The former group consumed less opioids, had
      fewer side-effects, and were more satisfied with their postoperative analgesia.
      Both groups showed an equally high degree of satisfaction with the new management
      pathway. Hospital stays, surgical outcomes, and frequency of complications were
      similar in the two groups. CONCLUSION. Continuous femoral nerve blockade proved
      to be a feasible and better alternative mode of postoperative analgesia than our
      conventional patient-controlled analgesia. Our new multidisciplinary management
      pathway and multimodal analgesic regimen featuring the continuous femoral nerve
      blockade appeared beneficial to patients and effective in our clinical setting. 

PMID- 24021936
TI  - COMPLETE-MFA: complementary parallel labeling experiments technique for metabolic
      flux analysis.
AB  - We have developed a novel approach for measuring highly accurate and precise
      metabolic fluxes in living cells, termed COMPLETE-MFA, short for complementary
      parallel labeling experiments technique for metabolic flux analysis. The COMPLETE
      MFA method is based on combined analysis of multiple isotopic labeling
      experiments, where the synergy of using complementary tracers greatly improves
      the precision of estimated fluxes. In this work, we demonstrate the COMPLETE-MFA
      approach using all singly labeled glucose tracers, [1-(13)C], [2-(13)C], [3
      (13)C], [4-(13)C], [5-(13)C], and [6-(13)C]glucose to determine precise metabolic
      fluxes for wild-type Escherichia coli. Cells were grown in six parallel cultures
      on defined medium with glucose as the only carbon source. Mass isotopomers of
      biomass amino acids were measured by gas chromatography-mass spectrometry (GC
      MS). The data from all six experiments were then fitted simultaneously to a
      single flux model to determine accurate intracellular fluxes. We obtained a
      statistically acceptable fit with more than 300 redundant measurements. The
      estimated flux map is the most precise flux result obtained thus far for E. coli
      cells. To our knowledge, this is the first time that six isotopic labeling
      experiments have been successfully integrated for high-resolution (13)C-flux
      analysis. 

PMID- 24021937
TI  - Angiotensin II induces C-reactive protein expression via AT1-ROS-MAPK-NF-kappaB
      signal pathway in hepatocytes.
AB  - BACKGROUND: C-reactive protein (CRP) participates in development of inflammatory
      diseases. Hepatocytes are a major contributor of circulating CRP. Although
      angiotensin II (Ang II) is known to evoke inflammatory response, it remains
      unknown whether Ang II induces CRP expression in hepatocytes. The present study
      observed effect of Ang II on CRP expression and the related signal pathway in
      hepatocytes. METHODS: mRNA and protein expressions in human hepatocytes were
      determined with RT-PCR and Western blot respectively. Reactive oxygen species
      (ROS) was measured using a fluorescence probe. CRP in liver and serum of rats was
      determined by immunohistochemistry and ELISA respectively. RESULTS: Ang II
      induced mRNA and protein expression of CRP in hepatocytes and increased CRP
      production in liver and CRP level in serum. Losartan reduced Ang II- induced CRP
      expression in hepatocytes. Losartan and thenoyltrifluoroacetone decreased Ang II
      stimulated ROS production. N-acetylcysteine antagonized Ang II-induced CRP
      expression. Losartan and N-acetylcysteine inhibited Ang II-activated ERK1/2.
      Unlike ERK1/2, only losartan inhibited Ang II-activated JNK. Furthermore,
      pyrrolidine dithiocarbamate abolished Ang II-induced CRP expression. CONCLUSION:
      Ang II has ability to induce CRP expression in hepatocytes in vitro and in vivo
      through AT1 receptor followed by ROS, MAPK and NF-kappaB signal pathway.

PMID- 24021938
TI  - Effects of guided breathing on blood pressure and heart rate variability in
      hypertensive diabetic patients.
AB  - OBJECTIVE: Our aim was to investigate medium-term effects of device-guided
      breathing on blood pressure (BP) and its capacity to improve the cardiovascular
      autonomic balance in hypertensive diabetic patients. This feasibility study was
      conceived as a proof-of-concept trial under real life conditions for
      justification of further investigations. METHODS: A randomized, controlled study
      (RCT) of the effects of device-guided slow breathing on top of usual care against
      usual care alone (including non-pharmacological and pharmacological treatment).
      The intervention included 12-min sessions of guided breathing performed daily for
      8 weeks. Treatment effects were assessed with ambulatory blood pressure
      monitoring (24h ABPM) and with spectral analysis of short-term heart rate
      variability (HRV) obtained during standardized modified orthostatic load. Thirty
      two subjects with diabetes and antihypertensive therapy were randomly assigned to
      both study groups. RESULTS: After 8 weeks of guided breathing, significant
      reductions were demonstrated in 24 h systolic BP (x+/-SEM: 126.1+/-3.0 vs 123.2+/
      2.7 mmHg, p=0.01), and in 24 h pulse pressure (PP, 53.6+/-2.6 vs. 51.3+/-2.5
      mmHg, p=0.01), whereas no significant impact in the control group was shown. The
      differences in treatment effects (delta mmHg, RESPeRATE(r) vs control) were
      significant only for PP (-2.3+/-0.8 vs +0.2+/-1.2 mmHg, p<0.05). Strong baseline
      dependence of treatment effects (delta systolic BP) was observed (p<0.01). Guided
      breathing showed a stronger treatment effect in terms of an increase in HRV,
      predominantly in low frequency band (p<0.03 vs. usual care). CONCLUSION: Even in
      well controlled hypertensive diabetic patients, guided breathing induced relevant
      effects on BP and HRV, finding which should be investigated further.

PMID- 24021939
TI  - Reduced sympathetic activity in idiopathic rapid-eye-movement sleep behavior
      disorder and Parkinson's disease.
AB  - BACKGROUND: More than 50% of patients with idiopathic REM sleep behavior disorder
      (iRBD) will develop Parkinson's disease or Lewy body dementia. In a previous
      study, we found attenuated heart rate responses in iRBD and Parkinson's disease
      patients during sleep. The current study aimed to evaluate heart rate variability
      further in order to identify possible changes in these components during
      wakefulness and sleep in patients with iRBD and Parkinson's disease. METHODS: We
      evaluated heart rate variability in 5-minute electrocardiography segments from
      wakefulness, and non-REM and REM sleep in 11 iRBD patients and 23 Parkinson's
      disease patients, and compared these with 10 control subjects. RESULTS AND
      CONCLUSIONS: Patients with iRBD had attenuated sympathetic nervous system
      activity compared with controls and this was more pronounced in patients with
      Parkinson's disease. The cardiac parasympathetic nervous system seems to be
      relatively well preserved in patients with iRBD and Parkinson's disease. The
      progressive reduction of sympathetic nervous activity is in line with the
      postganglionic sympathetic nervous dysfunction seen in early Parkinson's disease.

PMID- 24021940
TI  - Application of the Bethesda System for Reporting Thyroid Cytopathology in the
      Eastern Province of Saudi Arabia: phase I pilot retrospective analysis.
AB  - We analyzed and evaluated our adequacy rate and the classification of our thyroid
      aspirates using the Bethesda System for Reporting Thyroid Cytopathology (BSRTC).
      All thyroid fine needle aspirates that were collected or referred to our
      institution were reviewed and reclassified according to the BSRTC. The results
      were tabulated and analyzed. Those with histological resection were correlated
      with our revised cytopathological evaluation using the BSRTC. A total of 205
      thyroid aspirates from 186 patients were reviewed. There were 149 females (80%)
      and 37 males (20%) ranging in age from 23 to 81 (average age 48) years. All
      slides were reclassified using the BSRTC. The previous interpretations were not
      consistent with any apparent standards. The nondiagnostic rate was found to be
      22%. Five cases were considered false negative and were upgraded to a more
      serious category with higher risk of malignancy. The high unsatisfactory rates
      can be reduced by an adequacy interpretation at the time of the procedure. The
      risk of malignancy in our cohort increased with each increase in the BSRTC
      category (I-VI). Communication about and awareness of the BSRTC and its
      implications by all our clinicians is a prime target of this study and is still
      work in progress. Hopefully, this study will increase the awareness of the BSRTC
      and its intended benefits in our region.

PMID- 24021941
TI  - Anti-neuroinflammatory efficacy of the aldose reductase inhibitor FMHM via
      phospholipase C/protein kinase C-dependent NF-kappaB and MAPK pathways.
AB  - Aldose reductase (AR) has a key role in several inflammatory diseases: diabetes,
      cancer and cardiovascular diseases. Therefore, AR inhibition seems to be a useful
      strategy for anti-inflammation therapy. In the central nervous system (CNS),
      microglial over-activation is considered to be a central event in
      neuroinflammation. However, the effects of AR inhibition in CNS inflammation and
      its underlying mechanism of action remain unknown. In the present study, we found
      that FMHM (a naturally derived AR inhibitor from the roots of Polygala tricornis
      Gagnep.) showed potent anti-neuroinflammatory effects in vivo and in vitro by
      inhibiting microglial activation and expression of inflammatory mediators.
      Mechanistic studies showed that FMHM suppressed the activity of AR-dependent
      phospholipase C/protein kinase C signaling, which further resulted in downstream
      inactivation of the IkappaB kinase/IkappaB/nuclear factor-kappa B (NF-kappaB)
      inflammatory pathway. Therefore, AR inhibition-dependent NF-kappaB inactivation
      negatively regulated the transcription and expression of various inflammatory
      genes. AR inhibition by FMHM exerted neuroprotective effects in
      lipopolysaccharide-induced neuron-microglia co-cultures. These findings suggested
      that AR is a potential target for neuroinflammation inhibition and that FMHM
      could be an effective agent for treating or preventing neuroinflammatory
      diseases. 

PMID- 24021942
TI  - Treatment of fetal fibroblasts with DNA methylation inhibitors and/or histone
      deacetylase inhibitors improves the development of porcine nuclear transfer
      derived embryos.
AB  - This study investigated whether treating fetal fibroblast cells (donor cells)
      with epigenetic modification-inducing drugs could improve the development of
      porcine cloned embryos. Donor cells were treated with different DNA methylation
      inhibitors (5-aza-dC, zebularine or RG108; 5nM) or histone deacetylase inhibitors
      (TSA, NaBu or SCR; 50nM) for 1h, and then subjected to SCNT. All of the treated
      groups showed significantly higher blastocyst formation rates compared to the
      control group. We chose 5-aza-dC and TSA as a combined treatment, and found that
      donor cells co-treated with 2.5nM 5-aza-dC for 1h and subsequently treated with
      50nM TSA for another 1h before SCNT showed significantly improved blastocyst
      rates compared to the control, 5-aza-dC-treated, and TSA-treated groups. The
      levels of DNA methylation were decreased (though not to a significant degree) in
      donor cells treated with 5-aza-dC, TSA or both. The histone H3 acetylation levels
      were significantly increased in donor cells treated with TSA or co-treated with 5
      aza-dC and TSA. Donor cells simultaneously co-treated with 5nM 5-aza-dC and 50nM
      TSA for 1h showed increased apoptosis of SCNT blastocysts. However, when we
      decreased the concentration of 5-aza-dC to 2.5nM, the co-treatment induced less
      apoptosis among SCNT blastocysts and the blastocyst development rate improved.
      Together, these results indicate that treatment of donor cells with 5-aza-dC,
      TSA, or TSA plus a low dose of 5-aza-dC could improve the blastocyst development
      of porcine cloned embryos. 

PMID- 24021943
TI  - Targeting peripheral blood pro-inflammatory CD28null T cells and natural killer T
      like cells by inhibiting CD137 expression: possible relevance to treatment of
      bronchiolitis obliterans syndrome.
AB  - BACKGROUND: We have shown that bronchiolitis obliterans syndrome (BOS) is
      associated with attenuated suppression of pro-inflammatory cytokines and granzyme
      B by steroid-resistant peripheral blood CD28nullCD137+ T cells and natural killer
      T (NKT)-like cells. We hypothesized that we could target these steroid-resistant
      lymphocytes by inhibiting costimulation through CD137. METHODS: Isolated
      peripheral blood mononuclear cells from transplant patients with stable lung
      function, patients with BOS, and healthy controls were stimulated with anti-CD3
      with and without blocking anti-CD137 and with and without 10(-6) mol/liter
      methylprednisolone (MP) (with and without stimulatory anti-CD137). Pro
      inflammatory cytokine profiles and expression of the cytotoxic mediator, granzyme
      B, by CD28null T and NKT-like cells were determined using flow cytometry.
      RESULTS: There was a significant decrease in the percentage of CD28null T and NKT
      like cells producing interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha,
      and granzyme B in all individuals in the presence of anti-CD137 blocking antibody
      compared with anti-CD3 alone (eg, 30% decrease in CD8+CD28null TNF-alpha+ cells).
      Stimulatory anti-CD137 was associated with an increase in pro
      inflammatory/cytotoxic cells. Treatment with anti-CD137 blocking with
      prednisolone further reduced IFN-gamma, TNF-alpha, and granzyme B in these cells.
      CONCLUSIONS: Blocking CD137 expression in CD28null T cells and NKT-like cells is
      associated with down-regulation of IFN-gamma, TNF-alpha, and granzyme B.
      Targeting CD137 reduces pro-inflammatory/cytotoxic expression in steroid
      resistant CD28null T and NKT-like cells and may have therapeutic implications for
      patients with BOS.

PMID- 24021944
TI  - Gastrointestinal bleeding and subsequent risk of thromboembolic events during
      support with a left ventricular assist device.
AB  - BACKGROUND: Modern left ventricular assist devices (LVAD) require anti
      coagulation (AC) with warfarin and anti-platelet therapy to prevent
      thromboembolic complications in patients. Gastrointestinal bleeding (GI) is a
      significant adverse event in these patients and treatment typically requires
      reduction or elimination of AC or anti-platelet therapy. It is not known whether
      alterations in AC to treat GI bleeding influence subsequent risk of
      thromboembolic (TE) events during LVAD support. METHODS: Between July 2003 and
      September 2011, 389 patients (308 male) underwent implantation of a continuous
      flow LVAD at the University of Michigan Health System and the Mayo Clinic. Median
      age at implant was 60 years (range 18 to 79 years). Outcomes were analyzed for
      the association of GI bleeding events and subsequent TE events, defined as
      stroke, transient ischemic attack, hemolysis or suspected or confirmed pump
      thrombosis. RESULTS: Median survival was 10 months (maximum 7.2 years, total 439
      patient-years). TE events occurring within the first 30 days were not counted.
      Overall survival and freedom from an outcome event were assessed using the Kaplan
      Meier method. Associations between GI bleeding and subsequent TE events and
      survival impact were analyzed as time-dependent covariates. One hundred ninety
      nine GI bleeding episodes occurred in 116 of 389 patients (30%) for an event rate
      of 0.45 GI bleed/patient-year of support. One hundred thirty-eight TE events
      occurred in 97 of 389 patients (25%) for an event rate of 0.31 TE event/patient
      year of support. Median time from LVAD implant to first GI bleed was 5 months
      (range 1 to 116 months) and to first TE event was 6 months (range 1 to 29
      months). For patients who had a TE event after GI bleed, the median interval was
      5 months (range 0.5 to 25 months). TE events were 7.4-fold more likely in
      patients who had a prior GI bleed (range 4.9- to 11.1-fold) (p < 0.001); however,
      neither the presence of GI bleeding (0.7 to 1.2) nor a TE event (0.8 to 2.0)
      portended a lower overall survival. CONCLUSIONS: Patients who had GI bleeding
      were at significantly higher risk for a subsequent TE event. Although the exact
      cause of this relationship is unknown, it suggests that a reduction in anti
      coagulation and anti-platelet management to treat GI bleeds may contribute to
      this risk.

PMID- 24021945
TI  - Roost selection by female Hemprich's long-eared bats.
AB  - Selection of suitable roosts by bats can have fitness benefits by providing
      shelter and a place to rear young. Assuming that lactating bats behave
      differently from, and have greater food requirements than pregnant bats, we
      predicted that near the end of pregnancy, desert-dwelling bats would move to
      roosts appropriate to their changing needs. We followed radio-tagged pregnant and
      lactating female Hemprich's long-eared bats, Otonycteris hemprichii, to their
      roosts and characterized the shape of 38 roosts by measuring their linear
      dimensions, compass direction of the outer rock face, roost temperature (Tr) and
      the distance from the roost to the bats' main foraging site. We also compared
      roosts used by bats to randomly chosen "potential" roosts. During reproduction,
      female O. hemprichii roosted mainly in cracks. Throughout the bats' reproductive
      period, most of the roosts faced the morning sun. Temperatures in roosts used by
      pregnant bats or distances to their main foraging site were not different from
      those used by lactating individuals. However, pregnant females used horizontal
      cracks while lactating females used vertical cracks. Comparing roosts used by
      bats to "potential" roosts, we found that the former had smaller daily amplitudes
      of Tr than the "potential" ones. Female O. hemprichii used only a small number of
      the available roosts in the area, and re-used some of them year after year. We
      suggest that, in contrast to bats that live in temperate habitats, O. hemprichii
      do not need to seek roosts with temperature conditions specific to the periods of
      pregnancy or lactation because natural changes in Tr suffice, and other factors
      are involved in the decision to choose a roost or to abandon it. 

PMID- 24021946
TI  - Temporal maps in appetitive Pavlovian conditioning.
AB  - Previous research suggests animals may integrate temporal information into mental
      representations, or temporal maps. We examined the parameters under which animals
      integrate temporal information in three appetitive conditioning experiments. In
      Experiment 1 the temporal relationship between 2 auditory cues was established
      during sensory preconditioning (SPC). Subsequently, rats were given first order
      conditioning (FOC) with one of the cues. Results showed integration of the order
      of cues between the SPC and FOC training phases. In subsequent experiments we
      tested the hypothesis that quantitative temporal information can be integrated
      across phases. In Experiment 2, SPC of two short auditory cues superimposed on a
      longer auditory cue was followed by FOC of either one of the short cues, or of
      the long cue at different times in the cue. Contrary to our predictions we did
      not find evidence of integration of temporal information across the phases of the
      experiment and instead responding to the SPC cues in Experiment 2 appeared to be
      dominated by generalization from the FOC cues. In Experiment 3 shorter auditory
      cues were superimposed on a longer duration light cue but with asynchronous onset
      and offset of the superimposed cues. There is some evidence consistent with the
      hypothesis that quantitative discrimination of whether reward should be expected
      during the early or later parts of a cue could be integrated across experiences.
      However, the pattern of responding within cues was not indicative of integration
      of quantitative temporal information. Generalization of expected times of reward
      during FOC seems to be the dominant determinant of within-cue response patterns
      in these experiments. Consequently, while we clearly demonstrated the integration
      of temporal order in the modulation of this dominant pattern we did not find
      strong evidence of integration of precise quantitative temporal information. This
      article is part of a Special Issue entitled: Associative and Temporal Learning. 

PMID- 24021947
TI  - Raman study of vibrational dynamics of aminopropylsilanetriol in gas phase.
AB  - Raman spectrum of aminopropylsilanetriol (APST) in gas phase has been recorded at
      room temperature in macro chamber utilizing two-mirror technique over the sample
      tube. Unlike predominantly trans molecular conformation in condensed phase, the
      spectra of vapor show that the molecules are solely in gauche conformation with
      intramolecular hydrogen bond N...HO which reduces the molecular energy in respect
      to trans conformation by 0.152 eV. The assignment of the molecular spectra based
      on the DFT calculation is presented. The strong vibrational bands at 354 cm(-1),
      588 cm(-1) and 3022 cm(-1) are proposed for verifying the existence of the ring
      like, hydrogen bonded structure. Special attention was devoted to the high
      frequency region, where hydrogen bond vibrations are coupled to stretchings of
      amino and silanol groups.

PMID- 24021948
TI  - Spectroscopic, thermal analysis and DFT computational studies of salen-type
      Schiff base complexes.
AB  - A new series of metal(II) complexes of Co(II), Ni(II), Cu(II), Zn(II), and Pb(II)
      have been synthesized from a salen-type Schiff base ligand derived from o
      vanillin and 4-methyl-1,2-phenylenediamine and characterized by elemental
      analysis, spectral (IR, UV-Vis, (1)H NMR, (13)C NMR and EI-mass), molar
      conductance measurements and thermal analysis techniques. Coats-Redfern method
      has been utilized to calculate the kinetic and thermodynamic parameters of the
      metal complexes. The molecular geometry, Mulliken atomic charges of the studied
      compounds were investigated theoretically by performing density functional theory
      (DFT) to access reliable results to the experimental values. The theoretical
      (13)C chemical shift results of the studied compounds have been calculated at the
      B3LYP, PBEPBE and PW91PW91 methods and standard 6-311+G(d,p) basis set starting
      from optimized geometry. The comparison of the results indicates that B3LYP/6
      311+G(d,p) yields good agreement with the observed chemical shifts. The measured
      low molar conductance values in DMF indicate that the metal complexes are non
      electrolytes. The spectral and thermal analysis reveals that all complexes have
      octahedral geometry except Cu(II) complex which can attain the square planner
      arrangement. The presence of lattice and coordinated water molecules are
      indicated by thermograms of the complexes. The thermogravimetric (TG/DTG)
      analyses confirm high stability for all complexes followed by thermal
      decomposition in different steps.

PMID- 24021949
TI  - Synthesis, molecular docking and biological evaluation of new steroidal 4H
      pyrans.
AB  - A series of new steroidal 4H-pyrans (4-6) have been synthesized from steroidal
      alpha, beta-unsaturated ketones (1-3). The products (4-6) were characterized by
      IR, (1)H NMR, (13)C NMR, MS and analytical data. The interaction studies of
      compounds (4-6) with DNA were carried out by employing gel electrophoresis, UV
      vis and fluorescence spectroscopy. The gel electrophoresis pattern revealed that
      compounds (4-6) bind to DNA and also demonstrated that the compound 6 alone or in
      presence of Cu (II) causes the nicking of supercoiled pBR322. The compounds 4 and
      5 bind to DNA preferentially through electrostatic and hydrophobic interactions
      with Kb values found to be 5.3*10(3) and 3.7*10(3) M(-1), respectively,
      indicating the higher binding affinity of compound 4 towards DNA. The docking
      study suggested the intercalation of compounds in between the nucleotide base
      pairs. The cytotoxicity and genotoxicity of the newly synthesized compounds were
      checked by MTT and comet assay, respectively during which compound 6 showed
      potential behaviour.

PMID- 24021950
TI  - Activity, inhibition, and induction of cytochrome P450 2J2 in adult human primary
      cardiomyocytes.
AB  - Cytochrome P450 2J2 plays a significant role in the epoxidation of arachidonic
      acid to signaling molecules important in cardiovascular events. CYP2J2 also
      contributes to drug metabolism and is responsible for the intestinal clearance of
      ebastine. However, the interaction between arachidonic acid metabolism and drug
      metabolism in cardiac tissue, the main expression site of CYP2J2, has not been
      examined. Here we investigate an adult-derived human primary cardiac cell line as
      a suitable model to study metabolic drug interactions (inhibition and induction)
      of CYP2J2 in cardiac tissue. The primary human cardiomyocyte cell line
      demonstrated similar mRNA-expression profiles of P450 enzymes to adult human
      ventricular tissue. CYP2J2 was the dominant isozyme with minor contributions from
      CYP2D6 and CYP2E1. Both terfenadine and astemizole oxidation were observed in
      this cell line, whereas midazolam was not metabolized suggesting lack of CYP3A
      activity. Compared with recombinant CYP2J2, terfenadine was hydroxylated in
      cardiomyocytes at a similar K(m) value of 1.5 MUM. The V(max) of terfenadine
      hydroxylation in recombinant enzyme was found to be 29.4 pmol/pmol P450 per
      minute and in the cells 6.0 pmol/pmol P450 per minute. CYP2J2 activity in the
      cell line was inhibited by danazol, astemizole, and ketoconazole in submicromolar
      range, but also by xenobiotics known to cause cardiac adverse effects. Of the 14
      compounds tested for CYP2J2 induction, only rosiglitazone increased mRNA
      expression, by 1.8-fold. This cell model can be a useful in vitro model to
      investigate the role of CYP2J2-mediated drug metabolism, arachidonic acid
      metabolism, and their association to drug induced cardiotoxicity.

PMID- 24021951
TI  - Long-term clinical outcomes after aortic valve replacement using cryopreserved
      aortic allograft.
AB  - BACKGROUND: Although the frequency of biological valve use in treating aortic
      valve disease is increasing, the critical limiting factor, "structural
      deterioration," remains unresolved. Analysis of long-term outcomes after
      implantation of cryopreserved aortic allografts will yield further information
      related to the durability of the aortic allograft, possibly suggesting mechanisms
      underlying or strategies to prevent or treat the structural deterioration of
      biological valve substitutes. METHODS: A total of 840 cryopreserved aortic
      allografts implanted in the last 35 years were reviewed with clinical follow-up
      completed in 99% of the consecutive series. By June 2010, 285 implanted
      allografts had been surgically explanted, 288 patients died before allograft
      removal, and 267 patients are under continued follow-up. RESULTS: Cryopreserved
      aortic allografts were durable for more than 15 years in the middle-aged and
      older patient population. The estimated median time until structural
      deterioration was 20 years post-implantation, and 2 allografts have been
      functioning well for more than 30 years. Structural deterioration was
      independently related to the young age of the recipient, elderly age of the
      donor, severe obesity in the recipient, history of blood transfusion in the
      recipient, and full-root implantation technique. Infection of the implanted
      allograft necessitating reintervention rarely occurred. Reintervention for the
      allograft demonstrated 2% in-hospital mortality. CONCLUSIONS: Cryopreserved
      aortic allografts were durable for more than 15 years. Structural deterioration
      of aortic allografts was related to multiple factors. The age of the recipient
      and the donor, obesity and blood transfusion history of the recipient, and
      implantation technique were identified as the most important factors contributing
      to allograft failure.

PMID- 24021953
TI  - Intrapleural administration of gelatin-embedded, sustained-release basic
      fibroblast growth factor for the regeneration of emphysematous lungs in rats.
AB  - BACKGROUND: Intra-airway and intra-arterial administration of gelatin-embedded,
      sustained-release basic fibroblast growth factor has stimulated regeneration of
      emphysematous lungs in animal experiments, but these routes of administration may
      also cause harm. This study investigated the effectiveness of intrapleural
      administration of gelatin-embedded, sustained-release basic fibroblast growth
      factor. This animal experiment preceded our clinical trial of intrapleural
      administration of sustained-release basic fibroblast growth factor in patients
      with chronic obstructive pulmonary disease accompanied by pneumothorax. METHODS:
      Pulmonary emphysema was induced in Sprague-Dawley rats using porcine elastase.
      Gelatin-embedded, sustained-release basic fibroblast growth factor was
      administered via the left pleural cavity. The rats were divided into a group that
      received gelatin-embedded, sustained-release basic fibroblast growth factor
      (FGF(+) group, n = 6), and a group that did not (FGF(-)group, n = 6). Animals
      were sacrificed after 14 days, and the results were evaluated by histologic
      examination. RESULTS: In the FGF(+) group, the mean linear intercept value of the
      alveolar septa was significantly shorter on the treated side than on the
      untreated side (65.1 +/- 7.0 vs 114.4 +/- 7.5 MUm; P = .0005). There was no
      significant difference in the mean linear intercept value between the treated and
      untreated sides in the FGF(-) group. CONCLUSIONS: Intrapleural administration of
      sustained-release basic fibroblast growth factor induced lung regeneration in
      rats with elastase-induced pulmonary emphysema.

PMID- 24021954
TI  - Dysphagia caused by a left atrial myxoma.

PMID- 24021955
TI  - Conventional surgery, sutureless valves, and transapical aortic valve
      replacement: what is the best option for patients with aortic valve stenosis? A
      multicenter, propensity-matched analysis.
AB  - OBJECTIVE: Although surgical aortic valve replacement (SAVR) is the treatment of
      choice for patients with aortic valve stenosis, transcatheter aortic valve
      replacement (TAVR) and sutureless aortic valve replacement (SU-AVR) have shown
      good results. The aim of our multicenter, propensity-matched study was to compare
      the clinical and hemodynamic outcomes of surgical SAVR, transapical TAVR (TA
      TAVR), and SU-AVR. METHODS: We analyzed data from 566 TA-TAVR, 349 SAVR, and 38
      SU-AVR patients treated from January 2009 to March 2012. We used a propensity
      matching strategy to compare on-pump (SAVR, SU-AVR) and off-pump (TA-TAVR)
      surgical techniques. The outcomes were analyzed using multivariate weighted
      logistic regression or multinomial logistic analysis. RESULTS: In the matched
      cohorts, the 30-day overall mortality was significantly lower after SAVR than TA
      TAVR (7% vs 1.8%, P = .026), with no differences in mortality between SU-AVR and
      TA-TAVR. Multivariate analysis showed SU-AVR to have a protective effect,
      although not statistically significant, against aortic regurgitation, pacemaker
      implantation, and renal replacement therapy compared with TA-TAVR. Compared with
      TA-TAVR, SAVR demonstrated significant protection against aortic regurgitation
      (odds ratio, 0.04; P < .001) and a trend toward protection against death,
      pacemaker implantation, and myocardial infarction. The mean transaortic gradient
      was 10.3 +/- 4.4 mm Hg, 11 +/- 3.4 mm Hg, and 16.5 +/- 5.8 mm Hg in the TA-TAVR,
      SU-AVR, and SAVR patients, respectively. CONCLUSIONS: SAVR was associated with
      lower 30-day mortality than TA-TAVR. SAVR was also associated with a lower risk
      of postoperative aortic regurgitation compared with TA-TAVR. We did not find
      other significant differences in outcomes among matched patients treated with
      SAVR, SU-AVR, and TA-TAVR.

PMID- 24021956
TI  - Correction factors for source strength determination in HDR brachytherapy using
      the in-phantom method.
AB  - For the purpose of clinical source strength determination for HDR brachytherapy
      sources, the German society for Medical Physics (DGMP) recommends in their report
      13 the usage of a solid state phantom (Krieger-phantom) with a thimble ionization
      chamber. In this work, the calibration chain for the determination of the
      reference air-kerma rate Ka,100 and reference dose rate to waterDw,1 by
      ionization chamber measurement in the Krieger-phantom was modeled via Monte Carlo
      simulations. These calculations were used to determine global correction factors
      k(tot), which allows a user to directly convert the reading of an ionization
      chamber calibrated in terms of absorbed dose to water, into the desired quantity
      Ka,100 or Dw,1. The factor k(tot) was determined for four available (192)Ir
      sources and one (60)Co source with three different thimble ionization chambers.
      Finally, ionization chamber measurements on three MUSelectron V2 HDR sources
      within the Krieger-phantom were performed and Ka,100 was determined according to
      three different methods: 1) using a calibration factor in terms of absorbed dose
      to water with the global correction factor [Formula: see text] according DGMP 13
      2) using a global correction factor calculated via Monte Carlo 3) using a direct
      reference air-kerma rate calibration factor determined by the national metrology
      institute PTB. The comparison of Monte Carlo based [Formula: see text] with those
      from DGMP 13 showed that the DGMP data were systematically smaller by about 2
      2.5%. The experimentally determined [Formula: see text] , based on the direct
      Ka,100 calibration were also systematically smaller by about 1.5%. Despite of
      these systematical deviations, the agreement of the different methods was in
      almost all cases within the 1sigma level of confidence of the interval of their
      respective uncertainties in a Gaussian distribution. The application of Monte
      Carlo based [Formula: see text] for the determination of Ka,100 for three
      MUSelectron V2 sources revealed the smallest deviation to the manufacturer's
      source certificate. With the calculated [Formula: see text] for a (60)Co source,
      the user is now able to accurately determine Ka,100 of a HDR (60)Co source via in
      phantom measurement. Moreover, using the presented global correction factor
      [Formula: see text] , the user is able to determine the future source
      specification quantity Dw,1 with the same in-phantom setup.

PMID- 24021957
TI  - Auditory M50 and M100 sensory gating deficits in bipolar disorder: a MEG study.
AB  - OBJECTIVES: Auditory sensory gating deficits have been reported in subjects with
      bipolar disorder, but the hemispheric and neuronal origins of this deficit are
      not well understood. Moreover, gating of the auditory evoked components
      reflecting early attentive stage of information processing has not been
      investigated in bipolar disorder. The objectives of this study were to
      investigate the right and left hemispheric auditory sensory gating of the M50
      (preattentive processing) and M100 (early attentive processing) in patients
      diagnosed with bipolar I disorder by utilizing magnetoencephalography (MEG).
      METHODS: Whole-head MEG data were acquired during the standard paired-click
      paradigm in 20 bipolar I disorder patients and 20 healthy controls. The M50 and
      the M100 responses were investigated, and dipole source localizations were also
      investigated. Sensory gating were determined by measuring the strength of the M50
      and the M100 response to the second click divided by that of the first click
      (S2/S1). RESULTS: In every subject, M50 and M100 dipolar sources localized to the
      left and right posterior portion of superior temporal gyrus (STG). Bipolar I
      disorder patients showed bilateral gating deficits in M50 and M100. The bilateral
      M50 S2 source strengths were significantly higher in the bipolar I disorder group
      compared to the control group. LIMITATIONS: The sample size was relatively small.
      More studies with larger sample sizes are warranted. Bipolar subjects were taking
      a wide range of medications that could not be readily controlled for.
      CONCLUSIONS: These findings suggest that bipolar I disorder patients have
      auditory gating deficits at both pre-attentive and early attentive levels, which
      might be related to STG structural abnormality.

PMID- 24021958
TI  - Hyperthymic temperament and rapid reaction time in brightness preference.
AB  - BACKGROUND: It is well-known that Type A behavior pattern is characterized by
      hard-driving, competitive behavior and time urgency. Also, people with
      hyperthymic temperament are known to have high energy levels and are full of
      plans. It is therefore hypothesized that hyperthymic temperament is associated
      with rapid processing and fast reaction time in making decisions. METHODS: Using
      data from our previous experimental studies (N=58) examining brightness judgment
      and brightness preference, reaction time (RT) was investigated in relation to
      hyperthymic temperament scores and fMRI signal changes of the left inferior
      orbitofrontal cortex during brightness judgment. RESULTS: RT for brightness
      judgment was significantly shorter than RT for brightness preference. Significant
      associations were found between RT for brightness preference and hyperthymic
      temperament scores, and RT for brightness preference and fMRI signal changes of
      the left inferior orbitofrontal cortex whilst performing brightness preference
      task. Multiple regression analysis revealed that RT for brightness preference
      task was significantly and negatively associated with hyperthymic temperament
      scores, and significantly and positively associated with fMRI signal changes of
      the left inferior orbitofrontal cortex. LIMITATIONS: It is uncertain whether the
      findings of RT (around 1s) can be extrapolated to routine life (around 24h) and
      whether RT for brightness preference can be generalized to a variety of daily
      activities. CONCLUSIONS: The present findings suggest that hyperthymic
      temperament is associated with rapid processing. Further studies are required to
      overcome the above limitations.

PMID- 24021959
TI  - Predictors of relapse in patients with major depressive disorder in a 52-week,
      fixed dose, double blind, randomized trial of selegiline transdermal system
      (STS).
AB  - OBJECTIVE: We investigated patient and disease characteristics predictive of
      relapse of MDD during a 52-week placebo controlled trial of selegiline
      transdermal system (STS) to identify patient characteristics relevant for STS
      treatment. METHOD: After 10 weeks of open-label stabilization with STS, 322
      remitted patients with MDD were randomized to 52-weeks of double-blind treatment
      with STS (6 mg/24h) or placebo (PLB). Relapse was defined as Hamilton Depression
      Rating Scale (HAMD-17) score of >= 14 and a CGI-S score of >= 3 with at least 2
      point increase from the beginning of the double blind phase on 2 consecutive
      visits. Cox's proportional hazards regression was used to examine the effect of
      potential predictors (age, sex, age at onset of first MDD, early response
      pattern, number of previous antidepressant trials, severity of index episode,
      number of previous episodes, melancholic features, atypical features and anxious
      feature) on outcome. Exploratory analyses examined additional clinical variables
      (medical history, other psychiatric history, and individual items of HAM-D 28) on
      relapse. RESULTS: For all predictor variables analyzed, treatment Hazard Ratio
      (HR=0.48~0.54) was significantly in favor of STS (i.e., lower relapse risk than
      PLB). Age of onset was significantly predictive of relapse. Type, duration, and
      severity of depressive episodes, previous antidepressant trials, or demographic
      variables did not predict relapse. In additional exploratory analysis, eating
      disorder history and suicidal ideation were significant predictors of relapse
      after controlling for the effect of treatment in individual predictor analysis.
      CONCLUSIONS: While age of onset, eating disorder history and suicidal ideation
      were significant predictors, the majority of clinical and demographic variables
      were not predictive of relapse. Given the post-hoc nature of analysis, the
      findings need confirmation from a prospective study. It appears that selegiline
      transdermal system was broadly effective in preventing relapse across different
      subtypes and symptoms clusters of MDD.

PMID- 24021960
TI  - Genetic variants of the BDNF and DRD3 genes in bipolar disorder comorbid with
      anxiety disorder.
AB  - BACKGROUND: The high comorbidity rate between bipolar disorder (BP) and anxiety
      disorder (AD) has been studied in depth. This comorbidity is not as high in Han
      Chinese in Taiwan. Therefore, we explored the genetic effects BP comorbid with
      AD. METHODS: We recruited 1316 participants: 286 with BP-I, 681 with BP-II, and
      349 healthy Controls. Genotypes of the BDNF Val66Met and DRD3 Ser9Gly
      polymorphisms were determined using polymerase chain reactions plus restriction
      fragment length polymorphism analysis. RESULTS: The DRD3 Ser9Gly polymorphism was
      associated with BP-II comorbid with AD (BPII(+AD)), and the BDNF Val66Met
      polymorphism was associated with BP-I comorbid with AD (BPI(+AD)). An interaction
      between the Val/Val genotype of the BDNF Val66Met and Gly/Gly polymorphism of the
      DRD3 Ser9Gly was found in BPII(+AD), but not in BP-II not comorbid with AD (BPI(
      AD)) compared with healthy Controls. LIMITATION: The low comorbidity rate of AD
      in both BP subtypes, especially BP-I, limit generalizing our findings.
      CONCLUSION: The involvement of the dopaminergic pathway in AD was confirmed,
      particularly with BP-II rather than BP-I. Because the Val/Val genotype of the
      BDNF Val66Met polymorphism, rather than the other two polymorphisms, has been
      associated with anxiety, it seems to affect BP-I comorbid with AD without the
      involvement of the DRD3 Seg9Gly polymorphism, but may modify the involvement of
      DRD3 Gly/Gly in BP-II comorbid with AD.

PMID- 24021961
TI  - Antimicrobial peptide LL-37 and IDR-1 ameliorate MRSA pneumonia in vivo.
AB  - BACKGROUND: The only human cathelicidin, LL-37, and the innate defense regulator
      peptide IDR-1, which have been proven to have antimicrobial activity, represent
      essential elements of immunity. Our previous study showed that the peptide LL-37
      was protective in vitro to attenuate LTA-induced inflammatory effects.
      Methicillin-resistant staphylococcus aureus (MRSA) causes a multitude of serious
      and sometimes life-threatening diseases around the globe. However, the effect of
      LL-37 and IDR-1 in MRSA-induced pneumonia is unknown. In the present study, we
      explored the potential of LL-37 and IDR-1 in ameliorating MRSA-induced pneumonia
      in vivo. METHODS: C57BL/6 mice were randomly divided into four groups and
      perfused intratracheally with PBS, peptide, MRSA and MRSA plus peptide,
      respectively. Pulmonary tissue pathology, ELISA and quantitative RT-PCR were
      employed. The relative signal pathways were further explored by western blot
      analysis. RESULTS: Pathological analysis of the lung tissue sections demonstrated
      that, when compared with the MRSA-treated group, both the LL-37 and IDR-1 could
      ameliorate the MRSA-induced pneumonia. The phosphorylation of JNK and Akt were
      markedly decreased in the peptide plus MRSA-treated group compared with the MRSA
      treated group. Furthermore, both of them also reduced TNF-alpha and IL-6
      production in the bronchoalveolar lavage fluid (BALF) and serum in vivo.
      CONCLUSION: We report the first evidence of peptides inhibiting inflammation,
      decreasing the release of inflammatory cytokines and restoring pulmonary function
      in vivo. The antimicrobial peptide LL-37 and IDR-1 could ameliorate MRSA-induced
      pneumonia by exerting an anti-inflammatory property and attenuating pro
      inflammatory cytokine release, thus providing support for the hypothesis that
      both innate and synthetic peptides could protect against MRSA in vivo.

PMID- 24021962
TI  - Transcriptional regulation at the yeast nuclear envelope.
AB  - The spatial organization of the genome inside the nucleus affects many nuclear
      processes, such as DNA replication, DNA repair, and gene transcription. In
      metazoans, the nuclear periphery harbors mainly repressed genes that associate
      with the nuclear lamina. This review discusses how peripheral positioning is
      connected to transcriptional regulation in yeasts. Tethering of reporter genes to
      the nuclear envelope was found to result in transcriptional silencing. Similarly,
      repression of the silent mating type loci and subtelomeric genes is influenced by
      their position close to the nuclear envelope. In contrast, active genes are bound
      by nucleoporins and inducible genes associate with the nuclear pore complex upon
      activation. Taken together, these results portray the nuclear envelope as a
      platform for transcriptional regulation, both through activation at nuclear pores
      and silencing at the nuclear envelope. 

PMID- 24021963
TI  - MicroRNA-182 promotes tumor cell growth by targeting transcription elongation
      factor A-like 7 in endometrial carcinoma.
AB  - BACKGROUND/AIMS: Endometrial carcinoma (EC) is the most common gynecological
      malignancy among women worldwide. Despite its prevalence, the molecular
      mechanisms underlying endometrial carcinogenesis are poorly understood. The
      purpose of this study was to examine the role of microRNA-182 and its target gene
      transcription elongation factor A-like 7 (TCEAL7) in EC. METHODS: The expression
      of miR-182 in human normal endometrial epithelial cells (NEEC) and in three human
      endometrial carcinoma cell lines (HEC-1B, RL95-2 and AN3CA) was measured by qRT
      PCR, and the mRNA and protein expression of TCEAL7 were assessed in the same
      three endometrial carcinoma cell lines and NEEC by qRT-PCR and western blotting,
      respectively. Subsequently, the target of miR-182 was predicted by bioinformatics
      and confirmed using a luciferase assay. Cell proliferation and colony formation
      of RL95-2 cells were examined by MTT assay and crystal violet staining,
      respectively. The expression of NFkappaB-p65, c-Myc and cyclin D1 proteins was
      determined by Western blot analysis. RESULTS: MiR-182 was significantly
      upregulated and TCEAL7 was downregulated in EC cell lines compared to NEEC. We
      showed that MiR-182 binds directly to a conserved 8 bp sequence in the 3'-UTR of
      TCEAL7, and inhibition of miR-182 upregulated TCEAL7 mRNA and protein expression
      to levels comparable to those induced by lentiviral-mediated overexpression of
      TCEAL7. MiR-182 inhibition decreased cell proliferation and colony formation
      ability, downregulated the expression of the pro-proliferative genes c-Myc and
      cyclin D1, and inhibited NFkappaB activation, and these effects were mimicked by
      TCEAL7 overexpression. CONCLUSIONS: miR-182 acts as an oncogenic miRNA in EC,
      promoting cell proliferation by targeting the tumor suppressor gene TCEAL7 and
      modulating the activity of its downstream effectors c-Myc, cyclin D1 and
      NFkappaB.

PMID- 24021965
TI  - ABO blood-typing using an antibody array technique based on surface plasmon
      resonance imaging.
AB  - In this study, readily available antibodies that are used in standard
      agglutination tests were evaluated for their use in ABO blood typing by a surface
      plasmon resonance imaging (SPR imaging) technique. Five groups of antibodies,
      including mixed clones of anti-A, anti-B, and anti-AB, and single clones of anti
      A and anti-B, were used to construct the five-line detection arrays using a
      multichannel flow cell in the SPR imager. The red blood cell (RBC) samples were
      applied to a multichannel flow cell that was orthogonal to the detection line
      arrays for blood group typing. We found that the blood samples were correctly
      grouped in less than 12 min by the SPR imaging technique, and the results were
      consistent with those of the standard agglutination technique for all 60 samples.
      We found that mixed clones of antibodies provided 33%-68% greater change in the
      SPR signal than the single-clone antibodies. Applying the SPR imaging technique
      using readily available antibodies may reduce the costs of the antibodies,
      shorten the measurement time, and increase the throughput. 

PMID- 24021967
TI  - Characterization of flexible copolymer optical fibers for force sensing
      applications.
AB  - In this paper, different polymer optical fibres for applications in force sensing
      systems in textile fabrics are reported. The proposed method is based on the
      deflection of the light in fibre waveguides. Applying a force on the fibre
      changes the geometry and affects the wave guiding properties and hence induces
      light loss in the optical fibre. Fibres out of three different elastic and
      transparent copolymer materials were successfully produced and tested. Moreover,
      the influence of the diameter on the sensing properties was studied. The
      detectable force ranges from 0.05 N to 40 N (applied on 3 cm of fibre length),
      which can be regulated with the material and the diameter of the fibre. The
      detected signal loss varied from 0.6% to 78.3%. The fibres have attenuation
      parameters between 0.16-0.25 dB/cm at 652 nm. We show that the cross-sensitivies
      to temperature, strain and bends are low. Moreover, the high yield strength
      (0.0039-0.0054 GPa) and flexibility make these fibres very attractive candidates
      for integration into textiles to form wearable sensors, medical textiles or even
      computing systems. 

PMID- 24021964
TI  - Life cycle of cytosolic prions.
AB  - Prions are self-templating protein aggregates that were originally identified as
      the causative agent of prion diseases in mammals, but have since been discovered
      in other kingdoms. Mammalian prions represent a unique class of infectious agents
      that are composed of misfolded prion protein. Prion proteins usually exist as
      soluble proteins but can refold and assemble into highly ordered, self
      propagating prion polymers. The prion concept is also applicable to a growing
      number of non-Mendelian elements of inheritance in lower eukaryotes. While prions
      identified in mammals are clearly pathogens, prions in lower eukaryotes can be
      either detrimental or beneficial to the host. Prion phenotypes in fungi are
      transmitted vertically from mother to daughter cells during cell division and
      horizontally during mating or abortive mating, but extracellular phases have not
      been reported. Recent findings now demonstrate that in a mammalian cell
      environment, protein aggregates derived from yeast prion domains exhibit a prion
      life cycle similar to mammalian prions propagated ex vivo. This life cycle
      includes a soluble state of the protein, an induction phase by exogenous prion
      fibrils, stable replication of prion entities, vertical transmission to progeny
      and natural horizontal transmission to neighboring cells. Our data reveal that
      mammalian cells contain all co-factors required for cytosolic prion propagation
      and dissemination. This has important implications for understanding prion-like
      properties of disease-related protein aggregates. In light of the growing number
      of identified functional amyloids, cell-to-cell propagation of cytosolic protein
      conformers might not only be relevant for the spreading of disease-associated
      proteins, but might also be of more general relevance under non-disease
      conditions. 

PMID- 24021968
TI  - Through-the-wall localization of a moving target by two independent ultra
      wideband (UWB) radar systems.
AB  - In the case of through-the-wall localization of moving targets by ultra wideband
      (UWB) radars, there are applications in which handheld sensors equipped only with
      one transmitting and two receiving antennas are applied. Sometimes, the radar
      using such a small antenna array is not able to localize the target with the
      required accuracy. With a view to improve through-the-wall target localization,
      cooperative positioning based on a fusion of data retrieved from two independent
      radar systems can be used. In this paper, the novel method of the cooperative
      localization referred to as joining intersections of the ellipses is introduced.
      This method is based on a geometrical interpretation of target localization where
      the target position is estimated using a properly created cluster of the ellipse
      intersections representing potential positions of the target. The performance of
      the proposed method is compared with the direct calculation method and two
      alternative methods of cooperative localization using data obtained by
      measurements with the M-sequence UWB radars. The direct calculation method is
      applied for the target localization by particular radar systems. As alternative
      methods of cooperative localization, the arithmetic average of the target
      coordinates estimated by two single independent UWB radars and the Taylor series
      method is considered. 

PMID- 24021966
TI  - PTR-MS in Italy: a multipurpose sensor with applications in environmental, agri
      food and health science.
AB  - Proton Transfer Reaction Mass Spectrometry (PTR-MS) has evolved in the last
      decade as a fast and high sensitivity sensor for the real-time monitoring of
      volatile compounds. Its applications range from environmental sciences to medical
      sciences, from food technology to bioprocess monitoring. Italian scientists and
      institutions participated from the very beginning in fundamental and applied
      research aiming at exploiting the potentialities of this technique and providing
      relevant methodological advances and new fundamental indications. In this review
      we describe this activity on the basis of the available literature. The Italian
      scientific community has been active mostly in food science and technology, plant
      physiology and environmental studies and also pioneered the applications of the
      recently released PTR-ToF-MS (Proton Transfer Reaction-Time of Flight-Mass
      Spectrometry) in food science and in plant physiology. In the very last years new
      results related to bioprocess monitoring and health science have been published
      as well. PTR-MS data analysis, particularly in the case of the ToF based version,
      and the application of advanced chemometrics and data mining are also aspects
      characterising the activity of the Italian community. 

PMID- 24021969
TI  - Proof of concept of impact detection in composites using fiber bragg grating
      arrays.
AB  - Impact detection in aeronautical structures allows predicting their future
      reliability and performance. An impact can produce microscopic fissures that
      could evolve into fractures or even the total collapse of the structure, so it is
      important to know the location and severity of each impact. For this purpose,
      optical fibers with Bragg gratings are used to analyze each impact and the
      vibrations generated by them. In this paper it is proven that optical fibers with
      Bragg gratings can be used to detect impacts, and also that a high-frequency
      interrogator is necessary to collect valuable information about the impacts. The
      use of two interrogators constitutes the main novelty of this paper. 

PMID- 24021970
TI  - Practical strategies for stable operation of HFF-QCM in continuous air flow.
AB  - Currently there are a few fields of application using quartz crystal
      microbalances (QCM). Because of environmental conditions and insufficient
      resolution of the microbalance, chemical sensing of volatile organic compounds in
      an open system was as yet not possible. In this study we present strategies on
      how to use 195 MHz fundamental quartz resonators for a mobile sensor platform to
      detect airborne analytes. Commonly the use of devices with a resonant frequency
      of about 10 MHz is standard. By increasing the frequency to 195 MHz the frequency
      shift increases by a factor of almost 400. Unfortunately, such kinds of quartz
      crystals tend to exhibit some challenges to obtain a reasonable signal-to-noise
      ratio. It was possible to reduce the noise in frequency in a continuous air flow
      of 7.5 m/s to 0.4 Hz [i.e., sigma(tau) = 2 * 10-9] by elucidating the major
      source of noise. The air flow in the vicinity of the quartz was analyzed to
      reduce turbulences. Furthermore, we found a dependency between the acceleration
      sensitivity and mechanical stress induced by an internal thermal gradient. By
      reducing this gradient, we achieved reduction of the sensitivity to acceleration
      by more than one decade. Hence, the resulting sensor is more robust to
      environmental conditions such as temperature, acceleration and air flow. 

PMID- 24021971
TI  - A study on rational function model generation for TerraSAR-X imagery.
AB  - The Rational Function Model (RFM) has been widely used as an alternative to
      rigorous sensor models of high-resolution optical imagery in photogrammetry and
      remote sensing geometric processing. However, not much work has been done to
      evaluate the applicability of the RF model for Synthetic Aperture Radar (SAR)
      image processing. This paper investigates how to generate a Rational Polynomial
      Coefficient (RPC) for high-resolution TerraSAR-X imagery using an independent
      approach. The experimental results demonstrate that the RFM obtained using the
      independent approach fits the Range-Doppler physical sensor model with an
      accuracy of greater than 10-3 pixel. Because independent RPCs indicate absolute
      errors in geolocation, two methods can be used to improve the geometric accuracy
      of the RFM. In the first method, Ground Control Points (GCPs) are used to update
      SAR sensor orientation parameters, and the RPCs are calculated using the updated
      parameters. Our experiment demonstrates that by using three control points in the
      corners of the image, an accuracy of 0.69 pixels in range and 0.88 pixels in the
      azimuth direction is achieved. For the second method, we tested the use of an
      affine model for refining RPCs. In this case, by applying four GCPs in the
      corners of the image, the accuracy reached 0.75 pixels in range and 0.82 pixels
      in the azimuth direction. 

PMID- 24021972
TI  - [Liver transplant with donated graft after controlled cardiac death. Current
      situation].
AB  - An increasing pressure on the liver transplant waiting list, forces us to explore
      new sources, in order to expand the donor pool. One of the most interesting and
      with a promising potential, is donation after cardiac death (DCD). Initially,
      this activity has developed in Spain by means of the Maastricht type II donation
      in the uncontrolled setting. For different reasons, donation after controlled
      cardiac death has been reconsidered in our country. The most outstanding
      circumstance involved in DCD donation is a potential ischemic stress, that could
      cause severe liver graft cell damage, resulting in an adverse effect on liver
      transplant results, in terms of complications and outcomes. The complex and
      particular issues related to DCD Donation will be discussed in this review. 

PMID- 24021973
TI  - Implant stability change and osseointegration speed of immediately loaded
      photofunctionalized implants.
AB  - OBJECTIVES: This study evaluated the degree and rate of implant stability
      development for photofunctionalized dental implants in humans. MATERIALS AND
      METHODS: Thirty-three implants (7 patients) placed in the maxilla and immediate
      loaded were evaluated. Photofunctionalization was performed by treating implants
      with ultraviolet for 15 minutes immediately before placement. Implant stability
      was assessed by measuring the implant stability quotient (ISQ) weekly starting
      from implant placement up to 3 months. Osseointegration speed index (OSI),
      defined as ISQ increase per month, was also evaluated. RESULTS: The average ISQ
      for photofunctionalized implants at week 6 was 78.0, which was considerably
      higher than the average ISQ of 66.1, reported in literature for various as
      received implants after a longer healing time of 2 to 6 months. No stability dip
      was observed for photofunctionalized implants regardless of the initial ISQ
      values. The OSI for photofunctionalized implants was 6.3 and 3.1 when their
      initial ISQ was 65 to 70 and 71 to 75, respectively, whereas the OSI values for
      as-received implants calculated from literature ranged from -3.0 to 1.17 with an
      average of -0.10. CONCLUSIONS: Photofunctionalization accelerated and enhanced
      osseointegration of dental implants, providing novel and practical avenues for
      further advancement in implant therapy.

PMID- 24021974
TI  - Full-mouth rehabilitation with immediate loading of implants inserted with
      computer-guided flap-less surgery: a 3-year multicenter clinical evaluation with
      oral health impact profile.
AB  - OBJECTIVE: The purpose of this report is to present the clinical outcomes and
      patients' satisfaction of full-mouth rehabilitation using computer-aided flapless
      implant placement and immediate loading of a prefabricated prosthesis. MATERIALS
      AND METHODS: The study included 30 consecutive fully edentulous patients who
      received 312 implants. Mandible and maxilla were treated in the same surgical
      session with computer-guided flapless approach using the NobelGuide protocol.
      Prefabricated screw-retained fixed prostheses were inserted at the end of
      surgery. Clinical and radiographic evaluations were assessed at 6, 12, and 36
      months. At baseline and 6 months after surgery, patients answered Oral Health
      Impact Profile in Edentulous Adults questionnaire to assess satisfaction.
      RESULTS: The implant survival rate was 97.9%, whereas the average marginal bone
      loss was 1.9 +/- 1.3 mm after 3 years. At 6 months, patients showed significantly
      greater satisfaction with their fixed rehabilitation when compared with
      conventional dentures. CONCLUSIONS: The results of this study confirm that
      rehabilitation with a prefabricated fixed prosthesis supported by implants placed
      with NobelGuide protocol is a viable and predictable treatment and increases
      patients' satisfaction and improves oral health-related quality of life.

PMID- 24021975
TI  - The complete mitochondrial genome of the sycamore lace bug Corythucha ciliata
      (Hemiptera: Tingidae).
AB  - The complete mitochondrial genome of the sycamore lace bug, Corythucha ciliata,
      was sequenced in this study. It represents the first sequenced mitogenome of
      family Tingidae in Heteroptera. The mitogenome of C. ciliata is 15,257bp and
      contains 37 genes including 13 protein-coding genes (PCGs), 22 tRNA genes, two
      rRNA genes and a large non-coding region. Gene arrangement, nucleotide content,
      codon usage, and amino acid composition and asymmetry indicate a high degree of
      conservation with six other species of Cimicomorpha. The 13 PCGs initiated with
      ATN as the start codon and terminated with TAA, TA or T as stop codon. The
      evolutionary rate of each PCG was different, among which ATP8 showed the highest
      rate while ATP6 indicated the lowest rate. The 22 tRNAs genes apparently fold
      into a typical cloverleaf structure; however, the anticodon (TTC) of trnSer (AGN)
      differs from other Heteropteran insects. Secondary structure modeling of rRNA
      genes revealed similarity to other insects, except for two incomplete helices
      (H1648 and H2735) in lrRNA. The predicted secondary structure of lrRNA indicates
      45 helices in six domains, whereas srRNA has 27 helices in three domains. Three
      potential stem-loops and two tandem repeats (-TCTAAT-) were identified in the A+T
      rich region. Phylogenetic analysis indicated that C. ciliata is a sister group to
      other Heteroptera species based on analysis of the 13 PCGs. 

PMID- 24021976
TI  - Patterns of evolutionary selection pressure in the immune signaling protein
      TRAF3IP2 in mammals.
AB  - TRAF3 interacting protein 2 (TRAF3IP2) is important for immune responses to
      pathogens, inflammatory signals and autoimmunity in mammals. In the present
      study, we collected 19 mammalian TRAF3IP2 sequences and investigated the various
      types of selection pressure acting on them. Maximum likelihood estimations of
      nonsynonymous (dN) to synonymous (dS) substitution (dN/dS) ratios for the aligned
      coding sequences indicated that, as a whole, TRAF3IP2 has been subject to
      purifying selection. However, the N-terminus of the protein has been subject to
      higher selection pressure than the C-terminal domain. While eight amino acid
      residues within the N-terminus appear to have evolved under positive selection,
      no evidence for such selection was found in the C-terminus. The positively
      selected residues, which fall outside the currently known functional sites within
      TRAF3IP2, may have novel functions. The different selection pressures acting on
      the N- and C-terminal regions are consistent with their protein structures: the C
      terminal structure is an ordered structure, whereas the N-terminus is disordered.
      Taken together with the results of previous studies, it is plausible that
      positive selection on the N-terminus of TRAF3IP2 may have occurred by competitive
      coevolution between mammalian hosts and viruses.

PMID- 24021978
TI  - Ceramide synthases as potential targets for therapeutic intervention in human
      diseases.
AB  - Ceramide is located at a key hub in the sphingolipid metabolic pathway and also
      acts as an important cellular signaling molecule. Ceramide contains one acyl
      chain which is attached to a sphingoid long chain base via an amide bond, with
      the acyl chain varying in length and degree of saturation. The identification of
      a family of six mammalian ceramide synthases (CerS) that synthesize ceramide with
      distinct acyl chains, has led to significant advances in our understanding of
      ceramide biology, including further delineation of the role of ceramide in
      various pathophysiologies in both mice and humans. Since ceramides, and the
      complex sphingolipids generated from ceramide, are implicated in disease, the
      CerS might potentially be novel targets for therapeutic intervention in the
      diseases in which the ceramide acyl chain length is altered. This article is part
      of a Special Issue entitled New Frontiers in Sphingolipid Biology. 

PMID- 24021979
TI  - Urinary cytomorphology and clinical correlates of prostatic small cell
      neuroendocrine carcinoma.
AB  - BACKGROUND: Small cell carcinoma (SCC) of the prostate represents a rare form of
      prostatic carcinoma. While the tumor is often considered to arise from
      neuroendocrine proliferation or possibly dedifferentiation of an acinar
      carcinoma, the precise etiology remains uncertain. The diagnosis of prostatic SCC
      in urine has to date not been described. METHODS: A retrospective review was
      performed at a tertiary-care hospital, and 3 patients with prostatic SCC in
      voided urinary specimens were identified. The following clinical data were
      collected for each case: age, gender, treatment and follow-up information, when
      available. RESULTS: The patient age range was 70-86 years, all male. Two patients
      had known metastatic adenocarcinoma of the prostate, and 1 had recently presented
      with prostatic SCC. One patient with metastatic disease died shortly after
      diagnosis, the other was lost to follow-up. The third patient with a recent
      presentation has yet to have a treatment plan finalized. CONCLUSIONS: Our results
      highlight the importance of making this uncommon diagnosis as it may carry
      significant treatment and prognostic importance. Future work should hopefully
      clarify the role of ERG gene rearrangements in the pathogenesis of prostatic SCC,
      as there is a potential role here for targeted therapy.

PMID- 24021977
TI  - The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal
      barrier.
AB  - This review covers the background to discovery of the two key lipoxygenases (LOX)
      involved in epidermal barrier function, 12R-LOX and eLOX3, and our current views
      on their functioning. In the outer epidermis, their consecutive actions oxidize
      linoleic acid esterified in omega-hydroxy-ceramide to a hepoxilin-related
      derivative. The relevant background to hepoxilin and trioxilin biochemistry is
      briefly reviewed. We outline the evidence that linoleate in the ceramide is the
      natural substrate of the two LOX enzymes and our proposal for its importance in
      construction of the epidermal water barrier. Our hypothesis is that the oxidation
      promotes hydrolysis of the oxidized linoleate moiety from the ceramide. The
      resulting free omega-hydroxyl of the omega-hydroxyceramide is covalently bound to
      proteins on the surface of the corneocytes to form the corneocyte lipid envelope,
      a key barrier component. Understanding the role of the LOX enzymes and their
      hepoxilin products should provide rational approaches to ameliorative therapy for
      a number of the congenital ichthyoses involving compromised barrier function.
      This article is part of a Special Issue entitled The Important Role of Lipids in
      the Epidermis and their Role in the Formation and Maintenance of the Cutaneous
      Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias. 

PMID- 24021980
TI  - Active colitis exacerbates immune response to internalized food antigens in mice.
AB  - BACKGROUND: Previous studies have indicated that colitis increases intestinal
      permeability to food antigens. This condition also generates an immunoreactive
      milieu in the gut, which may exacerbate or counteract allergy reactions. This,
      along with the fact that both colitis and allergy are being codiagnosed more
      frequently, means the scientific interest on the immune relation between these
      pathologies is increasing. We evaluated the immune response to an internalized
      food antigen that was initiated during a concomitant active intestinal
      inflammatory response. METHODS: An ovalbumin (OVA)-induced immune response was
      analyzed in healthy mice and in mice suffering from colitis induced by the
      administration of dinitrofluorobenzene/dinitrosulfonic acid (DNFB/DNS) at the
      moment of OVA challenge. The OVA-induced clinical score and allergy response both
      in plasma and in splenocyte cultures from these animals were compared. RESULTS:
      Although no differences were observed in the allergy clinical score, the
      concomitant active colitis led to an increase in the immune response to OVA
      antigen, as shown by increased spleen size and OVA-induced splenocyte
      proliferation, exacerbated expression of total and OVA-specific IgG1 levels,
      increased colonic IL-4 expression and OVA-induced IL-4 and IL-5 cytokine
      expression in spleen cells. CONCLUSIONS: Our results indicate that animals with
      active colitis undergo an exacerbated immune response to an internalized antigen.
      This finding could be relevant for the allergy management of patients presenting
      simultaneously with chronic colitis.

PMID- 24021981
TI  - PPR proteins of green algae.
AB  - Using the repeat finding algorithm FT-Rep, we have identified 154
      pentatricopeptide repeat (PPR) proteins in nine fully sequenced genomes from
      green algae (with a total of 1201 repeats) and grouped them in 47 orthologous
      groups. All data are available in a database, PPRdb, accessible online at
      http://giavap-genomes.ibpc.fr/ppr. Based on phylogenetic trees generated from the
      repeats, we propose evolutionary scenarios for PPR proteins. Two PPRs are clearly
      conserved in the entire green lineage: MRL1 is a stabilization factor for the
      rbcL mRNA, while HCF152 binds in plants to the psbH-petB intergenic region. MCA1
      (the stabilization factor for petA) and PPR7 (a short PPR also acting on
      chloroplast mRNAs) are conserved across the entire Chlorophyta. The other PPRs
      are clade-specific, with evidence for gene losses, duplications, and horizontal
      transfer. In some PPR proteins, an additional domain found at the C terminus
      provides clues as to possible functions. PPR19 and PPR26 possess a
      methyltransferase_4 domain suggesting involvement in RNA guanosine methylation.
      PPR18 contains a C-terminal CBS domain, similar to the CBSPPR1 protein found in
      nucleoids. PPR16, PPR29, PPR37, and PPR38 harbor a SmR (MutS-related) domain
      similar to that found in land plants pTAC2, GUN1, and SVR7. The PPR-cyclins PPR3,
      PPR4, and PPR6, in addition, contain a cyclin domain C-terminal to their SmR
      domain. PPR31 is an unusual PPR-cyclin containing at its N terminus an
      OctotricoPeptide Repeat (OPR) and a RAP domain. We consider the possibility that
      PPR proteins with a SmR domain can introduce single-stranded nicks in the plastid
      chromosome. 

PMID- 24021982
TI  - Immune activation in amyloid-beta-related angiitis correlates with decreased
      parenchymal amyloid-beta plaque load.
AB  - BACKGROUND: Primary angiitis of the central nervous system (PACNS) is a rare but
      serious condition. A fraction of patients suffering from PACNS concurrently
      exhibit pronounced cerebral amyloid angiopathy (CAA) which is characterized by
      deposits of amyloid-beta (Abeta) in and around the walls of small and medium
      sized arteries of the brain. PACNS with CAA has been identified as a distinct
      disease entity, termed Abeta-related angiitis (ABRA). Evidence points to an
      immune reaction to vessel wall Abeta as the trigger of vasculitis. OBJECTIVE: To
      investigate whether the inflammatory response to Abeta has (1) any effect on the
      status of immune activation in the brain parenchyma and (2) leads to clearance of
      Abeta from brain parenchyma. METHODS: We studied immune activation and Abeta load
      by quantitative immunohistochemical analysis in brain parenchyma adjacent to
      affected vessels in 11 ABRA patients and 10 matched CAA controls. RESULTS: ABRA
      patients showed significantly increased immune activation and decreased Abeta
      loads in the brain parenchyma adjacent to affected vessels. CONCLUSION: Our
      results are in line with the hypothesis of ABRA being the result of an excessive
      immune response to Abeta and show that this can lead to enhanced clearance of
      Abeta from the brain parenchyma by immune-mediated mechanisms.

PMID- 24021991
TI  - Young adult former ever smokers: the role of type of smoker, quit attempts, quit
      aids, attitudes/beliefs, and demographics.
AB  - OBJECTIVE: Young adults who smoke are often nondaily users who either quit or
      transition into dependent smokers. Further, this age group often has been
      considered an extension of the adult population. This study aims to examine young
      adult former ever smokers to understand factors associated with their stopping
      smoking. METHOD: Telephone interviews were conducted in 2010 with 4401 young
      adults in Florida. We examined the association between former ever smokers and
      sociodemographics, smoking behavior, quit attempts, quit aids, and
      attitudes/beliefs about smoking. RESULTS: Thirty-seven percent of young adults
      were former smokers, 20% were current smokers, and 43% were never smokers. Former
      smokers were more likely to be female, situational smokers (compared to
      occasional or established), more likely to have stopped smoking without
      acknowledging making a quit attempt, less likely to have used a quit aid, and
      less likely to display pro-tobacco attitudes/beliefs. CONCLUSION: Young adult
      former and current smokers have unique patterns of smoking and stopping smoking.
      Young adults may require novel intervention techniques to promote prevention and
      cessation based on these unique smoking patterns. Future research is needed to
      understand motivations to quit smoking among young adults.

PMID- 24021993
TI  - Patient-provider communication and timely receipt of preventive services.
AB  - OBJECTIVE: To estimate the association between how patients rate their health
      care provider's communication and the receipt of six clinical preventive services
      recommended by the U.S. Preventive Services Task Force (USPSTF) and the Advisory
      Committee on Immunization Practices (ACIP). METHODS: This study used national
      data from the 2009 Medical Expenditure Panel Survey (MEPS). The samples (sizes
      vary by service) included individuals aged 18 years and older who have a usual
      source of care (USC). The outcomes indicated whether or not individuals received
      screening for breast cancer, cervical cancer, colon cancer, high cholesterol,
      hypertension, or were vaccinated against influenza per clinical guidelines.
      Multivariate logistic regression models were created for each dependent variable.
      The main independent variables consisted of ratings of four patient-provider
      communication behaviors. RESULTS: In unadjusted analyses, respondents who rated
      their providers' communication higher reported greater utilization of preventive
      services. After controlling for confounding variables, only receipt of mammograms
      remained significantly associated with better communication (p<0.05). Screening
      for cervical cancer, colon cancer, high cholesterol, and influenza vaccination
      approached significance with better communication (p<0.10). CONCLUSIONS: Patient
      provider communication is associated with receipt of regular mammograms.
      Clinicians should consider their medical dialogue with patients as a stimulus for
      appropriate screenings and vaccinations.

PMID- 24021994
TI  - Covalent binding of BMP-2 on surfaces using a self-assembled monolayer approach.
AB  - Bone morphogenetic protein 2 (BMP-2) is a growth factor embedded in the
      extracellular matrix of bone tissue. BMP-2 acts as trigger of mesenchymal cell
      differentiation into osteoblasts, thus stimulating healing and de novo bone
      formation. The clinical use of recombinant human BMP-2 (rhBMP-2) in conjunction
      with scaffolds has raised recent controversies, based on the mode of presentation
      and the amount to be delivered. The protocol presented here provides a simple and
      efficient way to deliver BMP-2 for in vitro studies on cells. We describe how to
      form a self-assembled monolayer consisting of a heterobifunctional linker, and
      show the subsequent binding step to obtain covalent immobilization of rhBMP-2.
      With this approach it is possible to achieve a sustained presentation of BMP-2
      while maintaining the biological activity of the protein. In fact, the surface
      immobilization of BMP-2 allows targeted investigations by preventing unspecific
      adsorption, while reducing the amount of growth factor and, most notably,
      hindering uncontrolled release from the surface. Both short- and long-term
      signaling events triggered by BMP-2 are taking place when cells are exposed to
      surfaces presenting covalently immobilized rhBMP-2, making this approach suitable
      for in vitro studies on cell responses to BMP-2 stimulation. 

PMID- 24021992
TI  - Impact of five modifiable lifestyle habits on the probability of cancer
      occurrence in a Japanese population-based cohort: results from the JPHC study.
AB  - OBJECTIVE: The present work aims to provide 10-year estimates of the probability
      of cancer occurrence in the Japanese population based on age, sex, and the
      pattern of adherence to five healthy lifestyle habits. METHODS: The study
      population consisted of 74,935 participants in the Japan Public Health Center
      Based Prospective Study (aged 45 to 74 years) who answered a 5-year follow-up
      questionnaire about various lifestyle habits between 1995 and 1999. The
      relationship between five previously identified healthy lifestyle habits (never
      smoking, moderate or no alcohol consumption, adequate physical activity, moderate
      salt intake, and appropriate body mass index) and cancer occurrence was assessed
      using a sex-specific parametric survival model. RESULTS: Compared to individuals
      not adhering to any of the five habits, never-smoking men had a nearly 30%
      reduction in the 10-year probability of cancer occurrence (e.g., 20.5% vs. 28.7%
      at age 70), and never-smoking women had a 16% reduction (e.g., 10.5% vs. 12.5% at
      age 70). Adherence to all five habits was estimated to reduce the 10-year
      probability of cancer occurrence by 1/2 in men and 1/3 in women. CONCLUSION: By
      quantifying the impact of lifestyle habits on the probability of cancer
      occurrence, this study emphasizes the importance of lifestyle improvement.

PMID- 24021995
TI  - The short-term prediction of preterm birth: a systematic review and diagnostic
      metaanalysis.
AB  - OBJECTIVE: To assess the diagnostic accuracy of fetal fibronectin (fFN), fetal
      breathing movements (FBM), and cervical length (CL) for the short-term prediction
      of preterm birth in symptomatic patients. STUDY DESIGN: Diagnostic metaanalysis
      using bivariate methods. RESULTS: Pooled sensitivities for fFN, FBM, and CL for
      delivery within 48 hours of testing were 0.62 (95% confidence interval [CI], 0.43
      0.78), 0.75 (95% CI, 0.57-0.87) and 0.77 (95% CI, 0.54-0.90), respectively.
      Pooled specificities for fFN, FBM, and CL for delivery within 48 hours were 0.81
      (95% CI, 0.74-0.86), 0.93 (95% CI, 0.75-0.98) and 0.88 (95% CI, 0.84-0.91).
      Pooled sensitivities for fFN, FBM, and CL for delivery within 7 days were 0.75
      (95% CI, 0.69-0.80), 0.67 (95% CI, 0.43-0.84), and 0.74 (95% CI, 0.58-0.85).
      Pooled specificities for fFN, FBM, and CL for delivery within 7 days were 0.79
      (95% CI, 0.76-0.83), 0.98 (95% CI, 0.83-1.00) and 0.89 (95% CI, 0.85-0.92). Based
      on a pretest probability of 10% for delivery within 48 hours, posttest
      probabilities (positive and negative) were 27% and 5% for fFN, 54% and 3% for
      fFN, and 42% and 3% for CL. For a pretest probability of 20% for delivery within
      7 days, posttest probabilities (positive and negative) were 48% and 7% for fFN,
      89% and 8% for FBM, and 63% and 7% for CL. CONCLUSION: In symptomatic patients,
      for fFN, absence of FBM, and CL have diagnostic use as predictors of delivery
      within 48 hours and within 7 days of testing. Absence of FBM appears to be the
      best test for predicting preterm birth.

PMID- 24021996
TI  - Stellate ganglion block for treating hot flashes: a viable treatment option or
      sham procedure?
AB  - Stellate ganglion block (SGB) has been used for over 70 years to treat various
      cervical pain syndromes. Over the past 8 years, 4 different groups have reported
      on SGB's effects on hot flashes from unblinded, open-label trials. Review of
      these studies has shown markedly disparate results in terms of the magnitude of
      hot flash reduction from Baseline with one trial showing a 90% reduction in hot
      flashes and 3 other trials showing 28-44% reductions in hot flashes. The
      inconsistencies in these results in addition to the known potentially large
      (>50%) placebo effects that can occur in randomized controlled hot flash clinical
      trials make it difficult to render any conclusions regarding the efficacy of SGB
      for hot flashes at this time. A randomized controlled trial, including a sham
      saline treatment arm, needs to be performed to properly assess SGB's effects on
      hot flashes, Methodological challenges with such a study design are addressed and
      several suggestions are proposed to manage these challenges. 

PMID- 24021997
TI  - Entangled judgments: expert preferences for adapting biodiversity conservation to
      climate change.
AB  - A major challenge facing conservation experts is how to adapt biodiversity
      planning and practice to the impacts of climate change. To date, most commonly
      advocated adaptation actions mirror conventional approaches (e.g. protected
      areas) despite decades of concern regarding their efficacy and widespread
      discussion of less conventional, interventionist actions. This survey of 160
      experts (scientists and practitioners with specialized knowledge of the
      implications of climate change for biodiversity conservation) seeks to explain
      this deep incongruity. Specifically, we quantify current preferences for a
      diverse set of adaptation actions, and examine the choice logics that underpin
      them. We find near unanimous agreement in principle with the need for extensive
      active management and restoration interventions given climate change. However,
      when interventionist actions are provided as options alongside conventional
      actions, experts overwhelming prefer the latter. Four hypotheses, developed by
      linking the conservation adaptation literature with that of preference formation
      and risk and decision making, explore enduring preferences for conventional
      actions. They are (1) judged most ecologically effective, least risky and best
      understood; (2) linked with pro-ecological worldviews, marked by positive
      affective feelings, and an aversion to the hubris of managing nature; (3) a
      function of trust in biodiversity governance; and/or (4) driven by demographic
      factors such as gender. Overall, we find that experts prefer conventional over
      unconventional actions because they are viewed as relatively more effective and
      less risky from an ecological point of view, and because they are linked with
      positive affect ratings, and worldviews that are strongly pro-ecological. We
      discuss the roles of value-based and affective cues in shaping policy outcomes
      for adaptation specifically, and sustainable resource management more broadly. 

PMID- 24021998
TI  - Encoding style and its relationships with schizotypal traits and impulsivity
      during adolescence.
AB  - This study intends to explore how individual differences in encoding style (i.e.
      how encoding is implicitly affected by pre-existing schemata, so called an
      internal style, versus by cues from the outside world, so called an external
      style) are associated with schizotypal traits and impulsivity expression during
      adolescence. Moreover, we aim to provide first evidence reliability for the
      encoding style questionnaire with an adolescent sample. 101 French-speaking
      community adolescents (Mage=16.06, S.D.age=2.01; 57 girls; primarily Caucasian)
      participated in a cross-sectional study. The whole sample filled out a battery of
      self-report questionnaires. Our data supports a positive association between a
      predominant internal encoding style, the level of positive and disorganized
      schizotypal traits, and a higher degree of urgency and sensation seeking
      impulsivity components. On the one hand, these results have clinical implications
      in the sense that a low level in implicit processing, namely encoding style, is
      involved in positive and disorganized schizotypal traits as well as in
      impulsivity. Schizotypal traits and impulsivity are two sets of traits that put
      youth at risk for the development of severe psychopathological states in
      adulthood. On the other hand, this research enables an increased understanding of
      encoding style by providing the first reliable assessment tool for French
      speaking adolescents. 

PMID- 24021999
TI  - More stressors prior to and during the course of bipolar illness in patients from
      the United States compared with the Netherlands and Germany.
AB  - Considerable data suggest that compared to some European countries, in the U.S.
      there are more childhood onset bipolar disorders, more adverse courses of
      illness, and greater treatment resistance. Psychosocial variables related to
      these findings have not been adequately explored. Therefore we analyzed
      psychosocial stressors in three time domains: childhood; the year prior to
      illness Onset; and the Last Episode from questionnaires in 968 outpatients (mean
      age 41) with bipolar I or II disorder; 676 from four sites in the U.S. and 292
      from three in the Netherlands and Germany (abbreviated here as Europe). Compared
      to the Europeans, those from the U.S. had significantly more stressors in
      childhood and prior to the last episode. Stressors prior to the last episode were
      related to: childhood stressors; an earlier age at illness onset; anxiety and
      substance abuse comorbidity; lower income; both parents having an affective
      illness; and feeling more stigma. These data suggest a greater prevalence of
      adverse life events in childhood and over the course of bipolar illness in the
      U.S. compared to the Netherlands and Germany. Clinical, therapeutic, and public
      health approaches to these illness-relevant stressors require further
      exploration. 

PMID- 24022000
TI  - Association of the GDNF gene with depression and heroin dependence, but not
      schizophrenia, in a Chinese population.
AB  - The association of seven GDNF tag SNPs with depression, heroin dependence (HD)
      and schizophrenia was evaluated in Chinese. An increased risk of HD and
      depression was associated with rs2910709 T/T genotype and rs884344 C allele,
      respectively, suggesting GDNF is a novel susceptibility gene for depression and
      HD. 

PMID- 24022001
TI  - The effects of GLUT1 on the survival of head and neck squamous cell carcinoma.
AB  - BACKGROUND/AIMS: Cancer cells require increased nutrient uptake to support a high
      rate of proliferation, and the overexpression of glucose transporters, in
      particular GLUT1, is a common characteristic of human malignancies. Here, we
      investigated the relationship between the expression of GLUT1 and cell viability,
      colony forming ability and apoptosis of head and neck squamous cell carcinoma
      (HNSCC) in vitro and in a xenograft mouse model in vivo. METHODS: Lentiviral
      mediated overexpression and knock-down of GLUT1 was performed in two oral cancer
      cell lines (CAL27 and SCC25). QRT-PCR and Western blot analysis were used to
      detect the mRNA and protein expression of GLUT1 and nuclear factor-kappa B
      (NFkappaB) p65 subunit. Cell viability and apoptosis were assessed by MTT and
      flow cytometry analyses, respectively. Colony formation assays were performed by
      staining with 0.5% crystal violet. The role of GLUT1 in HNSCC was examined in
      vivo through the generation of a CAL27 (or CAL27 with different transfections)
      nude mice xenograft model of HNSCC. RESULTS: GLUT1 overexpression promoted cell
      viability and colony formation whereas GLUT1 silencing had the opposite effect.
      GLUT1 knock-down significantly increased the number of Annexin V positive cells
      in both cell lines and GLUT1 overexpression had the opposite effect, indicating
      that GLUT1 modulates apoptosis. Xenograft mouse models of GLUT1 knockdown and
      overexpression showed that GLUT1 expression was associated with poor survival and
      increased tumor growth. GLUT1 overexpression significantly upregulated the
      expression of NFkappaB-p65, and this effect was reversed by inhibition of GLUT1
      expression. CONCLUSIONS: GLUT1 expression plays an important role in the survival
      of HNSCC, and its effects may be associated with the activation of the NFkappaB
      pathway.

PMID- 24022002
TI  - Troponin: more lessons to learn.

PMID- 24022003
TI  - The German Aortic Valve Registry (GARY): in-hospital outcome.
AB  - BACKGROUND: Aortic stenosis is a frequent valvular disease especially in elderly
      patients. Catheter-based valve implantation has emerged as a valuable treatment
      approach for these patients being either at very high risk for conventional
      surgery or even deemed inoperable. The German Aortic Valve Registry (GARY)
      provides data on conventional and catheter-based aortic procedures on an all
      comers basis. METHODS AND RESULTS: A total of 13 860 consecutive patients
      undergoing repair for aortic valve disease [conventional surgery and
      transvascular (TV) or transapical (TA) catheter-based techniques] have been
      enrolled in this registry during 2011 and baseline, procedural, and outcome data
      have been acquired. The registry summarizes the results of 6523 conventional
      aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass
      surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI).
      Patients undergoing catheter-based techniques were significantly older and had
      higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9%
      (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was
      2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery,
      and 5.1% (TV AVI) and AVI 7.7% (TA AVI). CONCLUSION: The in-hospital outcome
      results of this registry show that conventional surgery yields excellent results
      in all risk groups and that catheter-based aortic valve replacements is an
      alternative to conventional surgery in high risk and elderly patients.

PMID- 24022004
TI  - Chromosome segregation by the Escherichia coli Min system.
AB  - The mechanisms underlying chromosome segregation in prokaryotes remain a subject
      of debate and no unifying view has yet emerged. Given that the initial
      disentanglement of duplicated chromosomes could be achieved by purely entropic
      forces, even the requirement of an active prokaryotic segregation machinery has
      been questioned. Using computer simulations, we show that entropic forces alone
      are not sufficient to achieve and maintain full separation of chromosomes. This
      is, however, possible by assuming repeated binding of chromosomes along a
      gradient of membrane-associated tethering sites toward the poles. We propose
      that, in Escherichia coli, such a gradient of membrane tethering sites may be
      provided by the oscillatory Min system, otherwise known for its role in selecting
      the cell division site. Consistent with this hypothesis, we demonstrate that MinD
      binds to DNA and tethers it to the membrane in an ATP-dependent manner. Taken
      together, our combined theoretical and experimental results suggest the existence
      of a novel mechanism of chromosome segregation based on the Min system, further
      highlighting the importance of active segregation of chromosomes in prokaryotic
      cell biology. 

PMID- 24022005
TI  - Barriers to transmission of transcriptional noise in a c-fos c-jun pathway.
AB  - We explored how transcriptional noise propagates in gene-regulatory pathways by
      studying the induction of two downstream genes by transcription factors c-fos and
      c-jun. They are produced for a brief period following serum stimulation of cells
      and then activate the promoters of their target genes by binding to them as
      heterodimers. We found that, even though they are coordinately expressed at the
      population level, in individual cells the expression of c-fos and c-jun is noisy
      and uncorrelated with each other. The expression of the downstream genes is also
      noisy, but there is little or no effect of the noise in the upstream genes on the
      expression of the downstream genes. The noise is not transmitted, because the
      number of heterodimers present in single cells is relatively invariant, and the
      induction of downstream genes is insensitive to the number of heterodimers in
      individual cells. Sequestration of promoters of the downstream genes within
      compact chromatin is a likely cause of this insensitivity. These barriers to the
      propagation and amplification of noise are likely to be commonplace in higher
      eukaryotes. 

PMID- 24022006
TI  - A map of cell type-specific auxin responses.
AB  - In plants, changes in local auxin concentrations can trigger a range of
      developmental processes as distinct tissues respond differently to the same auxin
      stimulus. However, little is known about how auxin is interpreted by individual
      cell types. We performed a transcriptomic analysis of responses to auxin within
      four distinct tissues of the Arabidopsis thaliana root and demonstrate that
      different cell types show competence for discrete responses. The majority of
      auxin-responsive genes displayed a spatial bias in their induction or repression.
      The novel data set was used to examine how auxin influences tissue-specific
      transcriptional regulation of cell-identity markers. Additionally, the data were
      used in combination with spatial expression maps of the root to plot a
      transcriptomic auxin-response gradient across the apical and basal meristem. The
      readout revealed a strong correlation for thousands of genes between the relative
      response to auxin and expression along the longitudinal axis of the root. This
      data set and comparative analysis provide a transcriptome-level spatial breakdown
      of the response to auxin within an organ where this hormone mediates many aspects
      of development. 

PMID- 24022007
TI  - Downregulation of ubiquitin level via knockdown of polyubiquitin gene Ubb as
      potential cancer therapeutic intervention.
AB  - Ubiquitin is involved in almost every cellular process, and it is also known to
      be a stress-inducible protein. Based on previous reports that many types of
      cancer display an elevated level of ubiquitin, we hypothesized that this
      increased amount of ubiquitin is essential for the growth of cancer cells and
      that, consequently, the downregulation of ubiquitin may be a potential anti
      cancer treatment. We first found that the level of ubiquitin can be effectively
      downregulated via knockdown of a polyubiquitin gene, Ubb, with siRNA (Ubb-KD) and
      then demonstrated its anti-cancer effects in several cancer cell lines and
      xenograft mice. Ubb-KD resulted in the attenuation of TNFalpha-induced NF-kappaB
      activation, the stabilization of the tumor suppressor p53, and stress
      sensitization. Taken together, downregulation of ubiquitin through Ubb-KD is a
      potential anti-cancer treatment by inhibiting ubiquitination at multiple sites
      related to oncogenic pathways and by weakening the ability of cancer cells to
      overcome increased stress. 

PMID- 24022008
TI  - Short-term saccadic adaptation in patients with anisometropic amblyopia.
AB  - PURPOSE: Amblyopia is a developmental disorder characterized by impairment of
      spatiotemporal visual processing that also affects oculomotor and manual motor
      function. We investigated the effects of amblyopia on short-term visuomotor
      adaptation using a saccadic adaptation paradigm. METHODS: A total of 8 patients
      with anisometropic amblyopia and 11 visually-normal controls participated.
      Saccadic adaptation was induced using a double-step paradigm that displaced a
      saccadic visual target (at +/-19 degrees ) back toward central fixation by 4.2
      degrees  during the ongoing saccade. Three test blocks, preadaptation,
      adaptation, and postadaptation, were performed sequentially while participants
      viewed binocularly and monocularly with the amblyopic and fellow eyes
      (nondominant and dominant eyes in controls) in three separate sessions. The
      spatial and temporal characteristics of saccadic adaptation were measured.
      RESULTS: Patients exhibited diminished saccadic gain adaptation. The percentage
      change in saccadic gain was lower in patients during amblyopic eye and binocular
      viewing compared to controls. Saccadic latencies were longer, and saccadic gains
      and latencies were more variable in patients during amblyopic eye viewing. The
      time constants of adaptation were comparable between controls and patients under
      all viewing conditions. CONCLUSIONS: The short-term adaptation of saccadic gain
      was weaker and more variable in patients during amblyopic eye and binocular
      viewing. Our findings suggest that visual error information necessary for
      adaptation is imprecise in amblyopia, leading to reduced modulation of saccadic
      gain, and support the proposal that the error signal driving saccadic adaptation
      is visual.

PMID- 24022009
TI  - Myopia and glaucoma in the South Korean population.
AB  - PURPOSE: To examine the association between myopia and glaucoma, visual field
      defects, optic disc structural damage, and IOP in a population with a high
      prevalence of normal-tension glaucoma (NTG). METHODS: Data were included from
      13,433 participants in the 2008 to 2011 Korean National Health and Nutrition
      Examination Survey, a cross-sectional study. Spherical equivalent was used to
      define refractive status as emmetropia (-0.99 to 0.99 diopters [D]), mild myopia
      (-1.00 to -2.99 D), moderate myopia (-3.00 to -5.99 D), severe myopia (<-6 D),
      and hyperopia (>=+1.00D). Glaucoma was defined by International Society for
      Geographical and Epidemiological Ophthalmology (ISGEO) criteria. RESULTS:
      Compared with those with emmetropia, the odds of a glaucoma diagnosis were higher
      with moderate myopia (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.2-4.1)
      and severe myopia (OR 4.6, CI 2.3-9.4). Visual field defects were increased for
      mild myopia (OR 2.3, CI 1.2-4.5) and severe myopia (OR 20.9, CI 6.3-68.6). Optic
      disc structural damage was increased for moderate myopia (OR 1.8, CI 1.2-2.5) and
      severe myopia (OR 2.3, CI 1.5-3.7). Mean IOP was higher for mild myopia (14.4 mm
      Hg, CI 14.2-14.5 mm Hg), moderate myopia (14.7 mm Hg, CI 14.4-15.0 mm Hg), and
      severe myopia (14.7 mm Hg, CI 14.3-15.2 mmHg) compared with those with emmetropia
      (14.0 mm Hg, CI 13.9-14.1 mm Hg). CONCLUSIONS: In South Koreans, more severe
      myopia was associated with greater odds of glaucoma as defined by ISGEO criteria.

PMID- 24022010
TI  - UV-B-induced DNA damage and repair in the mouse lens.
AB  - PURPOSE: Epidemiologic studies have linked UV-B exposure to development of
      cortical cataracts, but the underlying molecular mechanism(s) is unresolved.
      Here, we used a mouse model to examine the nature and distribution of DNA
      photolesions produced by ocular UV-B irradiation. METHODS: Anesthetized mice, eye
      globes, or isolated lenses were exposed to UV-B. Antibodies specific for 6-4
      photoproducts (6-4 PPs) or cyclobutane pyrimidine dimers (CPDs) were used to
      visualize DNA adducts. RESULTS: Illumination of intact globes with UV-B-induced 6
      4 PP and CPD formation in cells of the cornea, anterior iris, and central lens
      epithelium. Photolesions were not detected in retina or lens cells situated in
      the shadow of the iris. Photolesions in lens epithelial cells were produced with
      radiant exposures significantly below the minimal erythemal dose. Lens epithelial
      cells rapidly repaired 6-4 PPs, but CPD levels did not markedly diminish, even
      over extended postirradiation recovery periods in vitro or in vivo. The repair of
      6-4 PPs did not depend on the proliferative activity of the epithelial cells,
      since the repair rate in the mitotically-active germinative zone (GZ) was
      indistinguishable from that of quiescent cells in the central epithelium.
      CONCLUSIONS: Even relatively modest exposures to UV-B produced 6-4 PP and CPD
      photolesions in lens epithelial cells. Cyclobutane pyrimidine dimer lesions were
      particularly prevalent and were repaired slowly if at all. Studies on sun-exposed
      skin have established a causal connection between photolesions and so-called UV
      signature mutations. If similar mechanisms apply in the lens, it suggests that
      somatic mutations in lens epithelial cells may contribute to the development of
      cortical cataracts.

PMID- 24022011
TI  - Intercellular adhesion molecule 1 mediates migration of Th1 and Th17 cells across
      human retinal vascular endothelium.
AB  - PURPOSE: Autoimmune inflammation of the retina causes vision loss in the majority
      of affected individuals. Th1 or Th17 cells initiate the disease on trafficking
      from the circulation into the eye across the retinal vascular endothelium. We
      investigated the ability of human Th1- and Th17-polarized cells to cross a
      simulated human retinal endothelium, and examined the role of IgG superfamily
      members in this process. METHODS: Th1- and Th17-polarized cell populations were
      generated from human peripheral blood CD4(+) T cells, using two Th1- and Th17
      polarizing protocols. Transendothelial migration assays were performed over 18
      hours in Boyden chambers, after seeding the transwell membrane with human retinal
      endothelial cells. In some assays intercellular adhesion molecule 1 (ICAM-1),
      vascular cell adhesion molecule 1 (VCAM-1), or activated leukocyte cell adhesion
      molecule (ALCAM) blocking antibody, or isotype- and concentration-matched control
      antibody, was added to the upper chambers. RESULTS: Th1- and Th17-polarized cells
      migrated equally efficiently across the human retinal endothelial monolayer. The
      percentage of IL-17(+) IFN-gamma(-) Th17-polarized cells was reduced following
      migration. Blocking ICAM-1, but not VCAM-1 or ALCAM, significantly reduced
      migration of Th1- and Th17-polarized cells for a majority of human donors.
      CONCLUSIONS: Taken in the context of other literature on transendothelial
      migration, our results illustrate the importance of investigating the specific
      tissue and vascular endothelium when considering helper T cell migration in
      autoimmune inflammation. Our findings further indicate that while generalizations
      about involvement of specific adhesion molecules in uveitis and other autoimmune
      disease may be possible, these may not apply to individual patients universally.
      The observations are relevant to the use of adhesion blockade for therapeutic
      purposes.

PMID- 24022012
TI  - TGF-beta3 stimulates stromal matrix assembly by human corneal keratocyte-like
      cells.
AB  - PURPOSE: We have previously shown that TGF-beta3 (T3) stimulates extracellular
      matrix (ECM) assembly while maintaining antifibrotic characteristics in a model
      using human corneal fibroblasts (HCFs). This model, however, requires non
      physiological levels of serum. In the current study, we tested whether T3 could
      stimulate human corneal keratocytes (HCKs) in vitro to assemble a functional ECM,
      while maintaining their characteristics. METHODS: Human corneal keratocytes and
      HCFs were isolated and cultured using 1% or 10% serum, respectively +/-T3. The
      constructs were processed for indirect immunofluorescence (IF), transmission
      electron microscopy (TEM), and qRT-PCR, analyzing for keratocyte marker,
      keratocan, and ECM components, collagen (col) types I, III, and V. RESULTS:
      Quantitative reverse transcriptase PCR data showed that keratocan, col I, and V
      were all upregulated in HCKs compared with HCFs, whereas col III was expressed at
      low levels in HCKs. Transforming growth factor beta 3 stimulation further
      enhanced the level of change. Without T3, HCK constructs were very thin,
      approximately 5 MUm; however, as with HCFs, upon stimulation with T3, HCK
      constructs increased in thickness by approximately 5-fold. Cell counts and ECM
      production revealed that HCKs assembled more ECM per unit area compared with
      HCFs, and IF revealed downregulation of fibrotic markers, col III, and
      thrombospondin-1, with T3 stimulation. Transmission electron microscopy data
      revealed aligned ECM with long fibrils for all conditions except HCK Controls.
      Human corneal keratocytes+T3 also showed denser collagen fibrils with more
      consistent fibril diameter. CONCLUSIONS: Overall, the data suggests that it is
      possible to stimulate matrix secretion and assembly by HCKs in vitro by using a
      single growth factor, T3.

PMID- 24022013
TI  - Identification of vascular endothelial side population cells in the choroidal
      vessels and their potential role in age-related macular degeneration.
AB  - PURPOSE: The neovascular form of age-related macular degeneration (AMD) is
      characterized by the growth of abnormal new blood vessels from the choroid,
      termed choroidal neovascularization (CNV). The origin of the new vessels in CNV,
      however, has not been elucidated fully to our knowledge. The purpose of this
      study is to identify vascular endothelial side population (SP) cells in the
      preexisting choroidal vessels, and investigate their potential role in AMD.
      METHODS: We made single cell suspensions of freshly isolated mouse choroidal,
      retinal, and brain tissue by enzymatic digestion. Vascular endothelial SP cells
      were isolated using flow cytometry based on the ability to efflux the DNA-binding
      dye, Hoechst 33342, via ATP-binding cassette (ABC) transporters. RESULTS: In the
      choroid, 2.8% of CD31+CD45- vascular endothelial cells (ECs) showed a typical SP
      staining pattern. They were not bone marrow-derived and possessed high colony
      forming capacity in vitro. They proliferated during laser-induced CNV in vivo. In
      contrast, stereotypic SP staining pattern was not observed in retinal and brain
      ECs. Retinal and brain EC-SP cells included increased SP populations with less
      colony-forming capacity within the SP compartment, because they contained cells
      with and without proliferative potential. The latter still could efflux the dye
      due to high levels of ABC transporters, such as ABCB1a, ABCC4, and ABCC6.
      CONCLUSIONS: The EC-SP cells in the choroid may represent vessel-residing
      endothelial stem/progenitor cells contributing mainly to angiogenesis, and may be
      useful for augmenting vascular regeneration or for developing new antiangiogenic
      therapy in AMD.

PMID- 24022014
TI  - The mucosal factors retinoic acid and TGF-beta1 induce phenotypically and
      functionally distinct dendritic cell types.
AB  - Non-inflammatory dendritic cell (DC) subsets play an essential role in preventing
      massive inflammation in mucosal tissues. We investigated whether mucosa-related
      factors, namely retinoic acid (RA) and transforming growth factor-beta (TGF
      beta1), can induce such DC types. DCs were differentiated from monocytes in the
      absence or presence TGF-beta1 and RA. The phenotype as well as responsiveness to
      bacterial ligands was studied in detail. Compared to monocyte-derived DCs
      (moDCs), the expression of co-stimulatory molecule CD86 and DC maturation marker
      CD83 were strongly reduced by RA and TGF-beta1. In addition, both RA- and TGF
      beta1-induced DCs showed strongly decreased responsiveness to stimulation with
      the bacterial ligands lipopolysaccharide and peptidoglycan, and produced
      significantly lower levels of the pro-inflammatory cytokines IL-12 and TNF-alpha
      compared to moDCs, whilst IL-10 production was not significantly reduced. DCs
      differentiated under the influence of RA uniquely expressed markers related to
      intestinal homing (CD103 and integrin beta7). In addition, CCR7, which mediates
      homing to lymph nodes, was expressed by DCs differentiated in the presence of RA,
      and also to a lesser extent by the other DC types. Furthermore, whereas moDCs and
      TGF-beta1-derived moDCs expressed high levels of CD32, RA-derived DCs lacked CD32
      expression but expressed high levels of CD64, suggesting that RA-DCs may
      primarily respond to soluble proteins and moDCs, and TGF-beta DCs to immune
      complexes. The data presented here support the hypothesis that the mucosal
      factors TGF-beta1 and RA, which can also be provided through dietary intake of
      dairy products, result in functionally and phenotypically distinct DC types with
      non-inflammatory properties.

PMID- 24022015
TI  - Introduction to the special section on sleep and ADHD.

PMID- 24022016
TI  - Case reports of sleep phenotypes of ADHD: from hypothesis to clinical practice.
AB  - OBJECTIVE: Five sleep ADHD phenotypes have been hypothesized: (a) the hypo
      arousal state of the "primary" form of ADHD, (b) the sleep phase advanced
      disorder, (c) sleep disordered breathing (SDB), (d) restless legs syndrome and/or
      periodic limb movements disorder (PLMD), and (e) epilepsy. METHOD: Five case
      reports are presented; each child but one underwent video-polysomnography.
      RESULTS: The first case report is an example of ADHD and SDB, with improvement of
      hypersomnolence after resolution of sleep apnea. The second case shows the impact
      of delayed sleep onset latency in the pathogenesis of ADHD, and the efficacy of
      melatonin. The third case report describes the association with PLMD, with
      amelioration after iron supplementation. The other two cases are examples of ADHD
      and epilepsy, with clinical improvement after antiepileptic treatment was
      started. CONCLUSION: A diagnostic and therapeutic algorithm should be designed to
      find the best first-line treatment for ADHD and sleep problems/epilepsy.

PMID- 24022017
TI  - A method for high fidelity optogenetic control of individual pyramidal neurons in
      vivo.
AB  - Optogenetic methods have emerged as a powerful tool for elucidating neural
      circuit activity underlying a diverse set of behaviors across a broad range of
      species. Optogenetic tools of microbial origin consist of light-sensitive
      membrane proteins that are able to activate (e.g., channelrhodopsin-2, ChR2) or
      silence (e.g., halorhodopsin, NpHR) neural activity ingenetically-defined cell
      types over behaviorally-relevant timescales. We first demonstrate a simple
      approach for adeno-associated virus-mediated delivery of ChR2 and NpHR transgenes
      to the dorsal subiculum and prelimbic region of the prefrontal cortex in rat.
      Because ChR2 and NpHR are genetically targetable, we describe the use of this
      technology to control the electrical activity of specific populations of neurons
      (i.e., pyramidal neurons) embedded in heterogeneous tissue with high temporal
      precision. We describe herein the hardware, custom software user interface, and
      procedures that allow for simultaneous light delivery and electrical recording
      from transduced pyramidal neurons in an anesthetized in vivo preparation. These
      light-responsive tools provide the opportunity for identifying the causal
      contributions of different cell types to information processing and behavior. 

PMID- 24022018
TI  - Evaluation of specific immune response in early P. aeruginosa infection in cystic
      fibrosis patients.

PMID- 24022019
TI  - Nasal potential difference measurements in diagnosis of cystic fibrosis: an
      international survey.
AB  - BACKGROUND: The role of nasal potential difference (NPD) measurement as a
      diagnostic test for cystic fibrosis (CF) is a subject of global controversy
      because of the lack of validation studies, clear reference values, and
      standardized protocols for diagnostic NPD. METHODS: To determine diagnostic NPD
      frequency, protocols, interpretation, and rater agreement, we surveyed the 18 NPD
      centres of the European Cystic Fibrosis Society Diagnostic Network Working Group.
      RESULTS: Fifteen centres reported performing 373 diagnostic NPDs in 2012. Most
      use the CFF-TDN-SOP (67%) and the chloride-free + isoproterenol response of the
      side with the largest response (47%) as diagnostic criteria and use centre
      specific reference ranges. Rater agreement for five NPD tracings - in general -
      was good, but poor in tracings with different responses between the two nostrils.
      CONCLUSIONS: NPD is frequently used as a diagnostic and research tool for CF.
      Performance is highly standardized, centre-specific reference ranges are
      established, and rater agreement - in general - is good. Centre-independent
      diagnostic criteria and reference ranges must be defined by multicentre
      validation studies to improve standardized interpretation for diagnostic use.

PMID- 24022021
TI  - CD28: direct and critical receptor for superantigen toxins.
AB  - Every adaptive immune response requires costimulation through the B7/CD28 axis,
      with CD28 on T-cells functioning as principal costimulatory receptor.
      Staphylococcal and streptococcal superantigen toxins hyperstimulate the T-cell
      mediated immune response by orders of magnitude, inducing a lethal cytokine
      storm. We show that to elicit an inflammatory cytokine storm and lethality,
      superantigens must bind directly to CD28. Blocking access of the superantigen to
      its CD28 receptor with peptides mimicking the contact domains in either toxin or
      CD28 suffices to protect mice effectively from lethal shock. Our finding that
      CD28 is a direct receptor of superantigen toxins broadens the scope of microbial
      pathogen recognition mechanisms. 

PMID- 24022020
TI  - Modeling Huntington disease in Drosophila: Insights into axonal transport defects
      and modifiers of toxicity.
AB  - Huntington disease (HD) is an inherited neurodegenerative disorder caused by a
      polyglutamine (polyQ) expansion in the huntingtin (Htt) gene. Despite years of
      research, there is no treatment that extends life for patients with the disorder.
      Similarly, little is known about which cellular pathways that are altered by
      pathogenic Huntingtin (Htt) protein expression are correlated with neuronal loss.
      As part of a longstanding effort to gain insights into HD pathology, we have been
      studying the protein in the context of the fruitfly Drosophila melanogaster. We
      generated transgenic HD models in Drosophila by engineering flies that carry a 12
      exon fragment of the human Htt gene with or without the toxic trinucleotide
      repeat expansion. We also created variants with a monomeric red fluorescent
      protein (mRFP) tag fused to Htt that allows in vivo imaging of Htt protein
      localization and aggregation. While wild-type Htt remains diffuse throughout the
      cytoplasm of cells, pathogenic Htt forms insoluble aggregates that accumulate in
      neuronal soma and axons. Aggregates can physically block transport of numerous
      organelles along the axon. We have also observed that aggregates are formed
      quickly, within just a few hours of mutant Htt expression. To explore mechanisms
      of neurodegeneration in our HD model, we performed in vivo and in vitro screens
      to search for modifiers of viability and pathogenic Htt aggregation. Our results
      identified several novel candidates for HD therapeutics that can now be tested in
      mammalian models of HD. Furthermore, these experiments have highlighted the
      complex relationship between aggregates and toxicity that exists in HD. 

PMID- 24022022
TI  - Characterization of six missense mutations in the tissue-nonspecific alkaline
      phosphatase (TNSALP) gene in Chinese children with hypophosphatasia.
AB  - AIMS: Hypophosphatasia, a rare inherited disease characterized by defective
      mineralization of bone and teeth, is caused by various mutations in the tissue
      nonspecific isoenzyme of alkaline phosphatase (TNSALP) gene. Our aim was to
      determine the mutations on TNSALP gene in three Chinese children diagnosed as
      having hypophosphatasia. METHODS: Genomic DNA was extracted from whole blood
      samples of patients and their parents. The TNSALP coding regions were then
      sequenced. Plasmids expressing wild-type or various mutants were built and in
      vitro studies were performed in order to determine whether these amino acid
      replacements could affect the TNSALP enzymatic activity. RESULTS: Six missense
      mutations were identified from three independent pedigrees. Of the six missense
      mutations, four were novel and two had been previously reported. The Y28D, A111T
      and T389N mutants displayed only negligible ALP activity in vitro compared to the
      wild-type (WT) TNSALP. The defect was mainly due to the significantly decreased
      protein expression in the 66 KD immature forms and the nearly undetectable
      protein expression in the 80 KD mature forms. Moreover, all three mutants had a
      dominant negative effect on the WT protein when co-transfected with TNSALP (WT).
      M219V and R136L mutants both exhibited partial enzymatic activities which were
      consistent with reduced protein expression in both forms of TNSALP which further
      exhibited moderate dominant-negative effect. In addition, Y388H mutant showed
      weak ALP activity. Western blot analysis indicated that the extreme reduction in
      signal from the mature forms of TNSALP could be the main cause of decreased
      enzymatic activity, since a strong signal was observed in the immature forms.
      CONCLUSION: Six missense mutations were identified in three Chinese
      hypophosphatasia pedigrees with subnormal serum ALP activity. Our results show
      that the low activity of serum ALP in the three patients is due mainly to a
      defect in the protein expression of the mutants. This may be the underling
      molecular mechanism for hypophosphatasia in these patients.

PMID- 24022023
TI  - Extraction of events and temporal expressions from clinical narratives.
AB  - This paper addresses an important task of event and timex extraction from
      clinical narratives in context of the i2b2 2012 challenge. State-of-the-art
      approaches for event extraction use a multi-class classifier for finding the
      event types. However, such approaches consider each event in isolation. In this
      paper, we present a sentence-level inference strategy which enforces consistency
      constraints on attributes of those events which appear close to one another. Our
      approach is general and can be used for other tasks as well. We also design novel
      features like clinical descriptors (from medical ontologies) which encode a lot
      of useful information about the concepts. For timex extraction, we adapt a state
      of-the-art system, HeidelTime, for use in clinical narratives and also develop
      several rules which complement HeidelTime. We also give a robust algorithm for
      date extraction. For the event extraction task, we achieved an overall F1 score
      of 0.71 for determining span of the events along with their attributes. For the
      timex extraction task, we achieved an F1 score of 0.79 for determining span of
      the temporal expressions. We present detailed error analysis of our system and
      also point out some factors which can help to improve its accuracy. 

PMID- 24022024
TI  - An investigation into the simultaneous enzymatic and SERRS properties of silver
      nanoparticles.
AB  - Investigation into the use of artificial enzymes has become an increasingly
      popular area of research due to the numerous advantages offered in comparison to
      protein enzymes. One particular area of research interest involves the use of
      metal nanoparticles as artificial enzymes. The peroxidase-like activity of a
      variety of nanoparticles has recently been shown and their use in a range of
      assay formats for the detection of various analytes has been explored. Herein the
      enzyme mimicking activity of silver nanoparticles is investigated using the
      peroxidase substrate 3,3',5',5'-tetramethylbenzidine (TMB). The peroxidase-like
      nature of these nanoparticles can be used in combination with surface enhanced
      resonance Raman scattering (SERRS) to provide a novel spectroscopic method of
      analysis. Negatively charged silver nanoparticles were investigated in
      combination with TMB using SERRS and it was found that upon formation of the
      oxidation intermediate of TMB, small clusters of positively charged nanoparticles
      were formed. The enzyme like behaviour of silver nanoparticles along with their
      use as a SERRS substrate is combined to demonstrate a simple and rapid method for
      the direct detection of hydrogen peroxide with a detection limit of 100 nM. 

PMID- 24022025
TI  - [New mutation in a Spanish family with hereditary hyperferritinemia-cataract
      syndrome].

PMID- 24022026
TI  - [Oleander intoxication: neurologic manifestations].

PMID- 24022027
TI  - [Legionella pneumophila pneumonia associated with the use of a home humidifier in
      an immunocompetent girl].
AB  - BACKGROUND AND OBJECTIVES: Legionellosis is an uncommon cause of pneumonia in
      children and even more exceptionally in healthy children. The purpose of this
      study is to describe the procedure which led to the identification of an unusual
      source of legionella infection, in a healthy girl, and highlight the need to
      adopt preventive measures. METHODOLOGY AND RESULTS: A 4-year old girl without any
      risk factors was diagnosed of pneumonia caused by Legionella pneumophila
      serogroup 1. After investigating the environment, it was found that the source of
      the transmission was a home humidifier. CONCLUSIONS: Despite the fact that this
      equipment is classified with a low probability of spreading legionella, a lack of
      cleanliness and maintenance of these machines can increase the risk of
      transmission of the bacteria. Therefore, healthcare professionals must give
      adequate advice to their patients about the care of this equipment and how to use
      these machines properly.

PMID- 24022028
TI  - [Alternatives to the current treatment of hereditary hemochromatosis].

PMID- 24022029
TI  - [Meta-analysis of randomized trials, heterogeneity and prediction intervals].

PMID- 24022030
TI  - [Extrapolation of results from clinical trials to heart failure patients
      hospitalized in Internal Medicine].

PMID- 24022031
TI  - Statins in heart failure--With preserved and reduced ejection fraction. An
      update.
AB  - HMG-CoA reductase inhibitors or statins beyond their lipid lowering properties
      and mevalonate inhibition exert also their actions through a multiplicity of
      mechanisms. In heart failure (HF) the inhibition of isoprenoid intermediates and
      small GTPases, which control cellular function such as cell shape, secretion and
      proliferation, is of clinical significance. Statins share also the peroxisome
      proliferator-activated receptor pathway and inactivate extracellular-signal
      regulated kinase phosphorylation suppressing inflammatory cascade. By down
      regulating Rho/Rho kinase signaling pathways, statins increase the stability of
      eNOS mRNA and induce activation of eNOS through phosphatidylinositol 3
      kinase/Akt/eNOS pathway restoring endothelial function. Statins change also
      myocardial action potential plateau by modulation of Kv1.5 and Kv4.3 channel
      activity and inhibit sympathetic nerve activity suppressing arrhythmogenesis.
      Less documented evidence proposes also that statins have anti-hypertrophic
      effects - through p21ras/mitogen activated protein kinase pathway - which
      modulate synthesis of matrix metalloproteinases and procollagen 1 expression
      affecting interstitial fibrosis and diastolic dysfunction. Clinical studies have
      partly confirmed the experimental findings and despite current guidelines new
      evidence supports the notion that statins can be beneficial in some cases of HF.
      In subjects with diastolic HF, moderately impaired systolic function, low b-type
      natriuretic peptide levels, exacerbated inflammatory response and mild
      interstitial fibrosis evidence supports that statins can favorably affect the
      outcome. Under the lights of this evidence in this review article we discuss the
      current knowledge on the mechanisms of statins' actions and we link current
      experimental and clinical data to further understand the possible impact of
      statins' treatment on HF syndrome.

PMID- 24022032
TI  - Progranulin peripheral levels as a screening tool for the identification of
      subjects with progranulin mutations in a Portuguese cohort.
AB  - BACKGROUND: Progranulin (PGRN) mutations are associated with different clinical
      phenotypes, including frontotemporal lobar degeneration (FTLD), corticobasal
      syndrome (CBS) and Alzheimer's disease (AD). As all pathogenic PGRN mutations
      identified so far cause disease through haploinsufficiency, determination of PGRN
      levels has been proposed as a reliable method to identify mutation carriers.
      OBJECTIVE: To evaluate the accuracy of peripheral PGRN levels in the
      identification of the PGRN mutation carriers detected thus far in our Portuguese
      cohort. METHODS: Serum PGRN levels were measured in 244 subjects (124 patients in
      the spectrum of FTLD, 2 asymptomatic descendants of a FTLD patient, 56 AD
      patients and 64 controls) by a novel commercial ELISA kit. RESULTS: Low PGRN
      levels were detected in 7 individuals (5 behavioral variant frontotemporal
      dementia, 1 CBS, and 1 still clinically unaffected) that constituted the group of
      the null PGRN mutation carriers previously identified in our molecular diagnostic
      laboratory. The pathogenic mutations found consisted of 4 insertion-deletions,
      causing frameshifts resulting in premature stop codons, 3 of which were novel. In
      addition, a normal PGRN level was found in a patient harboring a novel missense
      variant. For this novel ELISA kit, we established a PGRN cut-off level that
      identified with 100% accuracy the pathogenic mutation carriers. CONCLUSION: This
      study supports the use of a novel assay for the determination of PGRN levels as a
      screening procedure to identify patients harboring null PGRN mutations. This
      approach would significantly decrease the required PGRN mutation analysis
      workload and should be extended to other clinical phenotypes than behavioral
      variant frontotemporal dementia and to apparently sporadic cases.

PMID- 24022034
TI  - Clinical Review. Personality disorder.

PMID- 24022033
TI  - Effectiveness of interdisciplinary primary care approach to reduce disability in
      community dwelling frail older people: cluster randomised controlled trial.
AB  - OBJECTIVE: To evaluate whether an interdisciplinary primary care approach for
      community dwelling frail older people is more effective than usual care in
      reducing disability and preventing (further) functional decline. DESIGN: Cluster
      randomised controlled trial. SETTING: 12 general practices in the south of the
      Netherlands PARTICIPANTS: 346 frail older people (score >= 5 on Groningen Frailty
      Indicator) were included; 270 (78%) completed the study. INTERVENTIONS: General
      practices were randomised to the intervention or control group. Practices in the
      control group delivered care as usual. Practices in the intervention group
      implemented the "Prevention of Care" (PoC) approach, in which frail older people
      received a multidimensional assessment and interdisciplinary care based on a
      tailor made treatment plan and regular evaluation and follow-up. MAIN OUTCOME
      MEASURES: The primary outcome was disability, assessed at 24 months by means of
      the Groningen Activity Restriction Scale. Secondary outcomes were depressive
      symptomatology, social support interactions, fear of falling, and social
      participation. Outcomes were measured at baseline and at 6, 12, and 24 months'
      follow-up. RESULTS: 193 older people in the intervention group (six practices)
      received the PoC approach; 153 older people in the control group (six practices)
      received care as usual. Follow-up rates for patients were 91% (n=316) at six
      months, 86% (n=298) at 12 months, and 78% (n=270) at 24 months. Mixed model
      multilevel analyses showed no significant differences between the two groups with
      regard to disability (primary outcome) and secondary outcomes. Pre-planned
      subgroup analyses confirmed these results. CONCLUSIONS: This study found no
      evidence for the effectiveness of the PoC approach. The study contributes to the
      emerging body of evidence that community based care in frail older people is a
      challenging task. More research in this field is needed. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN31954692.

PMID- 24022035
TI  - The word "cancer": how language can corrupt thought.

PMID- 24022036
TI  - International standards on informed patient consent are available.

PMID- 24022037
TI  - When a doctor goes wrong.

PMID- 24022038
TI  - Good quality patient leaflets are prerequisite to concordance between patients
      and healthcare professionals.

PMID- 24022039
TI  - The case for investing in high quality information for patients.

PMID- 24022040
TI  - Transparency for each research article. Institutions must also be accountable for
      research integrity.

PMID- 24022041
TI  - Harnessing clinical solving abilities through safety reporting to drive quality
      improvement in the NHS.

PMID- 24022042
TI  - Misgivings about PROSPERO in solving the problem of duplicate systematic reviews.

PMID- 24022043
TI  - The anaesthetic roundabout and its effect on behaviour at work.

PMID- 24022044
TI  - Health risk from job insecurity needs to be mitigated in these "VUCA times".

PMID- 24022045
TI  - The case for duplication of meta-analyses and systematic reviews.

PMID- 24022046
TI  - Duplicate systematic reviews. Repeated meta-analyses are both worthy and to be
      encouraged.

PMID- 24022047
TI  - Post-diagnostic support services should be included in new dementia targets.

PMID- 24022048
TI  - Government was wrong to prioritise "gold" route for open access, say MPs.

PMID- 24022049
TI  - UK government bows to pressure over lobbying bill.

PMID- 24022050
TI  - Nearly half of US births were covered by Medicaid in 2010.

PMID- 24022051
TI  - GMC seeks powers to test doctors' language skills.

PMID- 24022052
TI  - Anti-Markovnikov hydrophosphoroselenoylation of alkenes using phosphorodiselenoic
      acid esters leading to the formation of phosphonoselenoic acid esters.
AB  - Phosphorodiselenoic acid esters with a binaphthyl group were reacted with alkenes
      in the presence of Bu3SnH and AIBN to give phosphonoselenoic acid esters in
      moderate to good yields. The addition of a phosphoroselenoyl group to alkenes
      proceeded in an anti-Markovnikov fashion. The diastereoselectivity was improved
      by the introduction of substituents to 3,3'-positions of a binaphthyl group. 

PMID- 24022053
TI  - Therapeutic Silencing of Bcl-2 by Systemically Administered siRNA
      Nanotherapeutics Inhibits Tumor Growth by Autophagy and Apoptosis and Enhances
      the Efficacy of Chemotherapy in Orthotopic Xenograft Models of ER (-) and ER (+)
      Breast Cancer.
AB  - Bcl-2 is overexpressed in about a half of human cancers and 50-70% of breast
      cancer patients, thereby conferring resistance to conventional therapies and
      making it an excellent therapeutic target. Small interfering RNA (siRNA) offers
      novel and powerful tools for specific gene silencing and molecularly targeted
      therapy. Here, we show that therapeutic silencing of Bcl-2 by systemically
      administered nanoliposomal (NL)-Bcl-2 siRNA (0.15 mg siRNA/kg, intravenous) twice
      a week leads to significant antitumor activity and suppression of growth in both
      estrogen receptor-negative (ER(-)) MDA-MB-231 and ER-positive (+) MCF7 breast
      tumors in orthotopic xenograft models (P < 0.05). A single intravenous injection
      of NL-Bcl-2-siRNA provided robust and persistent silencing of the target gene
      expression in xenograft tumors. NL-Bcl-2-siRNA treatment significantly increased
      the efficacy of chemotherapy when combined with doxorubicin in both MDA-MB-231
      and MCF-7 animal models (P < 0.05). NL-Bcl-2-siRNA treatment-induced apoptosis
      and autophagic cell death, and inhibited cyclin D1, HIF1alpha and Src/Fak
      signaling in tumors. In conclusion, our data provide the first evidence that in
      vivo therapeutic targeting Bcl-2 by systemically administered nanoliposomal-siRNA
      significantly inhibits growth of both ER(-) and ER(+) breast tumors and enhances
      the efficacy of chemotherapy, suggesting that therapeutic silencing of Bcl-2 by
      siRNA is a viable approach in breast cancers.Molecular Therapy-Nucleic Acids
      (2013) 2, e121; doi:10.1038/mtna.2013.45; published online 10 September 2013. 

PMID- 24022054
TI  - The use of chromatographic techniques for the separation and the identification
      of insect lipids.
AB  - The paper presents the state of knowledge on the chromatographic techniques used
      in the analysis of insect lipids. Lipids are one of the forms of protection
      against entomopathogenic fungi. Their composition may include a number of
      different compounds, such as long chain hydrocarbons, waxes, alcohols, aldehydes
      and free fatty acids. These compounds may be presented in different amounts
      depending on the species of insects, living environment, lifestyle, seasons, etc.
      The most commonly used techniques in the analysis of lipids of insects are: gas
      chromatography, high performance liquid chromatography, and combined techniques
      such as gas chromatography-mass spectrometry (GC-MS) and liquid chromatography
      mass spectrometry (LC-MS). Compounds present in the cuticular lipids of insects
      may serve diverse functions such as minimizing transpiration. It was also found
      that extracts of insects possess antifungal effects. Determination of lipid
      profiles and biological activity of the identified compounds can effectively
      contribute to the knowledge of the defense mechanisms of insects, and thus,
      impact the development of new methods of combating harmful insects. 

PMID- 24022056
TI  - Simultaneous determination of gallic acid and gentisic acid in organic anion
      transporter expressing cells by liquid chromatography-tandem mass spectrometry.
AB  - In order to elucidate the role of organic anion transporters (OATs) in the renal
      elimination of gallic acid and gentisic acid, a new, rapid, and sensitive liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and
      validated for the simultaneous determination of gallic acid and gentisic acid in
      cell lysate, using Danshensu as the internal standard (IS). After a simple liquid
      liquid extraction, the analytes were detected in negative ESI mode using selected
      reaction monitoring. The precursor-to-product ion transitions (m/z) were 169.0
      >125.0, 153.1->108.0, and 196.8->135.2 for gallic acid, gentisic acid, and the
      IS, respectively. Chromatographic separation was achieved on a C18 column using
      mobile phases consisting of water with 0.1% acetic acid (A) and acetonitrile with
      0.05% formic acid. (B) The total run time was 3min and calibration curves were
      linear over the concentrations of 0.33-2400ng/mL for both compounds (r(2)>0.995).
      Good precision (between 3.11% and 14.1% RSD) and accuracy (between -12.7% and 11%
      bias) was observed for quality controls at concentrations of 0.33 (lower limit of
      quantification), 1, 50, and 2000ng/mL. The mean extraction recovery of gallic
      acid and gentisic acid was 80.7% and 83.5%, respectively. Results from post
      column infusion and post-extraction methods indicated that the analytical method
      exhibited negligible matrix effects. Finally, this validated assay was
      successfully applied in a cellular uptake study to determine the intracellular
      concentrations of gallic acid and gentisic acid in OAT expressing cells. 

PMID- 24022055
TI  - Adsorption properties and preparative separation of phenylethanoid glycosides
      from Cistanche deserticola by use of macroporous resins.
AB  - A simple and efficient chromatographic method for large-scale preparative
      separation of phenylethanoid glycosides (mainly contain echinacoside and
      acteoside) from Cistanche deserticola was developed. The adsorption properties of
      eight macroporous resins were evaluated. Three selected resins were further
      screened depending on the adsorption kinetics curves, in which HPD300 resin
      showed the best separation efficiency. The adsorption isotherm data on HPD300
      resin were fitted to the Freundlich equation in certain concentration range. The
      dynamic adsorption and desorption experiments were carried out on columns packed
      with HPD300 resin to optimize the separation process. The breakthrough curves
      showed that acteoside had a higher affinity to the resin than echinacoside. The
      contents of echinacoside and acteoside in the product increased from 1.79% and
      1.43% in the crude extracts to 16.66% and 15.17%, with recovery yields of 80.41%
      and 90.17%, respectively. The purity of total phenylethanoid glycosides in the
      product was 76.58%. 

PMID- 24022057
TI  - Cervical cancer rates after the transition from annual Pap to 3-year HPV and Pap.
AB  - OBJECTIVE: Kaiser Permanente Northern California (KPNC) introduced 3-year Pap and
      human papillomavirus DNA cotesting for cervical cancer screening in women 30
      years or older in 2003 to 2004. Patient and provider willingness to extend
      screening intervals and the impact on annual cervical cancer incidence after
      interval extension are evaluated. MATERIALS AND METHODS: Age-adjusted cervical
      cancer rates and screening intervals were calculated from KPNC Regional
      Laboratory databases and Northern California Cancer Registry from 2000 to 2009.
      RESULTS: The median screening interval between negative cotests was 36 months
      compared to the 16 months after a negative Pap test alone before the
      implementation of cotesting. The age-adjusted invasive cancer rate was 6.5 per
      100,000 women in 2000 and 6.3 in 2009; there was no difference in the rates of
      cervical cancer in women 30 years or older from 2000 to 2009 (p(trend) = .7).
      CONCLUSIONS: Patients and providers were compliant with the extension of
      screening intervals with cotesting. Cervical cancer rates remained constant
      during the 10-year study period despite extending screening intervals after a
      negative cotest.

PMID- 24022058
TI  - Ethanol assisted synthesis of pure and stable amorphous calcium carbonate
      nanoparticles.
AB  - Stable monodispersed amorphous calcium carbonate (ACC) nanoparticles can be
      synthesized in ethanol media by a facile method, and crystallization of ACC is
      kinetically controlled, resulting in the formation of three polymorphs in a mixed
      solvent of ethanol-water at different pH values. 

PMID- 24022059
TI  - Label-free nanometer-resolution imaging of biological architectures through
      surface enhanced Raman scattering.
AB  - Label free imaging of the chemical environment of biological specimens would
      readily bridge the supramolecular and the cellular scales, if a chemical
      fingerprint technique such as Raman scattering can be coupled with super
      resolution imaging. We demonstrate the possibility of label-free super-resolution
      Raman imaging, by applying stochastic reconstruction to temporal fluctuations of
      the surface enhanced Raman scattering (SERS) signal which originate from
      biomolecular layers on large-area plasmonic surfaces with a high and uniform hot
      spot density (>1011/cm2, 20 to 35 nm spacing). A resolution of 20 nm is
      demonstrated in reconstructed images of self-assembled peptide network and
      fibrilated lamellipodia of cardiomyocytes. Blink rate density is observed to be
      proportional to the excitation intensity and at high excitation densities (>10
      kW/cm2) blinking is accompanied by molecular breakdown. However, at low powers,
      simultaneous Raman measurements show that SERS can provide sufficient blink rates
      required for image reconstruction without completely damaging the chemical
      structure.

PMID- 24022061
TI  - Synthesis and nanostructures of several tetrathiafulvalene derivatives having the
      side chains composed of chiral and hydrogen-bonding groups and their charge
      transfer complexes.
AB  - Tetrathiafulvalene (TTF) derivatives TTF-Bor, TTF-2UM and TTF-4UM having chiral
      urethane groups were prepared. Among them, TTF-2UM, TTF-4UM and their charge
      transfer (CT) complexes with F4TCNQ organized the nanowires. The intermolecular
      hydrogen bonding of the chiral urethane groups and pi-stacking of TTF moieties or
      the formation of CT complexes resulted in a long one-dimensional nanowires. The
      chiral moieties were responsible for the molecular orientation of TTF cores to
      give helical structures. Electronic conductivity of the films of nanowires
      composed of TTF-2UM and TTF-4UM with F4TCNQ were determined to be 8.0 * 10(-2)
      and 3.2 * 10(-2) S cm(-1), respectively. 

PMID- 24022062
TI  - Magnetic composite photocatalyst ZnFe2O4/BiVO4: synthesis, characterization, and
      visible-light photocatalytic activity.
AB  - Magnetic composite ZnFe2O4/BiVO4 was successfully synthesized by the one-step
      chemical coprecipitation method. The photocatalytic activity of BiVO4 was
      improved by doping ZnFe2O4 that possessed a narrow band gap, which enabled the
      ZnFe2O4/BiVO4 composite to show increased visible-light absorption and further
      generate more photo-produced electrons than pure BiVO4. The experimental results
      showed that the photocatalytic ability of the composite was better than that of
      pure BiVO4 under visible light irradiation. The n-type ZnFe2O4 nanoparticles were
      uniformly distributed on the surface of n-type BiVO4, leading to the formation of
      n-n-type heterogeneous structures in the composite system. Since CB and VB
      potentials of ZnFe2O4 and BiVO4 were differential, the photo-produced electrons
      and holes would migrate to a position at a relatively positive potential and a
      relatively negative potential, respectively, which enhanced the separation
      efficiency between photo-produced electrons and holes and thus further
      contributed to the enhancement of photocatalytic activity. 

PMID- 24022063
TI  - Loss of all three calreticulins, CRT1, CRT2 and CRT3, causes  enhanced
      sensitivity to water stress in Arabidopsis.
AB  - KEY MESSAGE: The calreticulin triple knockout mutant shows growth defects in
      response to abiotic stress. The endoplasmic reticulum (ER) is an essential
      organelle that is responsible for the folding and maturation of proteins. During
      ER stress, unfolded protein aggregates accumulate in the cell, leading to the
      unfolded protein response (UPR). The UPR up-regulates the expression of ER-stress
      responsive genes encoding calreticulin (CRT), an ER-localized Ca2+-binding
      protein. To understand the function of plant CRTs, we generated a triple knockout
      mutant, t123, which lacks CRT1, CRT2 and CRT3 and examined the roles of
      calreticulins in abiotic stress tolerance. A triple knockout mutant increased
      sensitivity to water stress which implies that calreticulins are involved in the
      Arabidopsis response to water stress. We identified that the cyclophilin AtCYP21
      2, which is located in the ER, was specifically enhanced in the t123 mutants.
      Seed germination of the atcyp21-1 mutant was retarded by water stress. Taken
      together, these results suggest that regulatory proteins that serve to protect
      plants from water stress are folded properly in part with the help of
      calreticulins. The AtCYP21-2 may also participate in this protein-folding process
      in association with calreticulins.

PMID- 24022064
TI  - Seed coat pigmentation in transgenic soybean expressing the silencing suppressor
      2b gene of Cucumber mosaic virus.
AB  - KEY MESSAGE: Soybean expressing the Cucumber mosaic virus 2b gene manifests seed
      coat pigmentation due to suppression of endogenous RNA silencing but no other
      morphological abnormality. This gene may help prevent transgene silencing. RNA
      silencing is an important mechanism for gene regulation and antiviral defense in
      plants. It is also responsible for transgene silencing, however, and thus hinders
      the establishment of transgenic plants. The 2b protein of Cucumber mosaic virus
      (CMV) functions as a suppressor of RNA silencing and therefore might prove
      beneficial for stabilization of transgene expression. We have now generated
      transgenic soybean that harbors the 2b gene of a CMV-soybean strain under the
      control of a constitutive promoter to investigate the effects of 2b expression.
      No growth abnormality was apparent in 2b transgenic plants, although the seed
      coat was pigmented in several of the transgenic lines. Genes for chalcone
      synthase (CHS), a key enzyme of the flavonoid pathway, are posttranscriptionally
      silenced by the inhibitor (I) locus in nonpigmented (yellow) soybean seeds. The
      levels of CHS mRNA and CHS small interfering RNA in strongly pigmented 2b
      transgenic seed coats were higher and lower, respectively, than those in the seed
      coat of a control transgenic line. The expression level of 2b also correlated
      with the extent of seed coat pigmentation. On the other hand, introduction of the
      2b gene together with the DsRed2 gene into somatic embryos prevented the time
      dependent decrease in transient DsRed2 expression. Our results indicate that the
      2b gene alone is able to suppress RNA silencing of endogenous CHS genes regulated
      by the I locus, and that 2b is of potential utility for stabilization of
      transgene expression in soybean without detrimental effects other than seed coat
      pigmentation.

PMID- 24022065
TI  - Insulin resistance is associated with coronary plaque vulnerability: insight from
      optical coherence tomography analysis.
AB  - AIMS: Previous studies have reported that insulin resistance plays an important
      role in the progression of atherosclerosis. However, the relationship between
      insulin resistance and coronary plaque instability is not well established. The
      purpose of this study was to assess the relationship between insulin resistance
      and coronary plaque characteristics identified by optical coherence tomography
      (OCT). METHODS AND RESULTS: This study enrolled 155 consecutive patients
      undergoing percutaneous coronary intervention. OCT image acquisitions were
      performed in the culprit lesions. Insulin resistance was identified using the
      homeostasis model assessment of insulin resistance (HOMA-IR). Subjects were
      divided into three tertiles according to the HOMA-IR values. Patients in the
      higher HOMA tertile had more frequent prevalence of lipid-rich plaques than those
      in the middle and lower tertiles (83 vs. 62 vs. 57%; P = 0.01). The thin-cap
      fibroatheroma (TCFA) prevalence rates among the higher (>2.5), middle (1.4-2.5),
      and lower HOMA-IR (<1.4) tertiles were 50, 29, and 26% (P = 0.02). The
      microvessel prevalence rates of the three tertiles were 54, 39, and 28% (P =
      0.02). Furthermore, in the higher HOMA-IR group, the fibrous cap was
      significantly thinner compared with the other two tertiles (vs. lower HOMA-IR, P
      = 0.009; vs. middle HOMA-IR, P = 0.008). On multivariate analysis, acute coronary
      syndrome [odds ratio (OR): 17.98; 95% confidence interval (CI): 7.12-52.02; P <
      0.0001] and HOMA-IR >2.50 (OR: 3.57; 95% CI: 1.42-9.55; P = 0.007) were
      independent predictors for the presence of TCFA. CONCLUSION: This study suggests
      that insulin resistance might be associated with coronary plaque vulnerability.

PMID- 24022066
TI  - Neointimal patterns obtained by optical coherence tomography correlate with
      specific histological components and neointimal proliferation in a swine model of
      restenosis.
AB  - AIMS: Although optical coherence tomography (OCT) is capable to detect
      microscopic peri-strut changes that seem to be related to neointimal inhibition
      and healing, its ability to characterize these components is still limited. In
      this study, we aimed to compare different OCT morphological characteristics with
      different in-stent neointimal tissue types analysed by histology. METHODS: A
      total of 69 stents (39 drug eluting and 30 bare metal stents) were implanted in
      coronary arteries of 27 swine. By OCT, neointimal type was classified as
      homogeneous, heterogeneous, or layered according to its pattern of backscatter
      and optical intensity. The resulting optical patterns were correlated with
      several histological findings [external elastic lamina (EEL) disruption, fibrin
      deposition, circumferential rim of peri-strut inflammatory cell infiltration, and
      fibrous connective deposition] in every single cross-section (CS) analysed.
      RESULTS: A total of 197 matched OCT and histological CS were analysed. The
      heterogeneous (0.44 +/- 0.21 mm) and layered (0.65 +/- 0.16 mm) patterns had a
      significantly higher degree of neointimal thickness compared with the homogeneous
      pattern (0.25 +/- 0.16 mm, P < 0.001). Fibrous connective tissue deposition was
      more frequently present in the homogeneous pattern (71.6%, P < 0.001), whereas
      significant fibrin deposits were more commonly seen in the heterogeneous pattern
      (56.9%, P = 0.007). Peri-strut inflammation was less frequently found in the
      homogeneous pattern (19.8%, P < 0.001) in comparison with the layered (73.9%) or
      heterogeneous patterns (43.1%). The presence of EEL rupture was also more
      commonly seen in layered (73.9%) and heterogeneous (46.6%) patterns than in the
      homogeneous pattern (22.4%, P < 0.001). CONCLUSION: The optical characteristics
      of neointimal formation seen in OCT properly correlated with the presence of
      several histological findings involved in stent healing. The biological
      implications of these findings in clinical outcomes require further
      investigation.

PMID- 24022067
TI  - A multidisciplinary intervention to reduce antibiotic duration in lower
      respiratory tract infections.
AB  - OBJECTIVES: Prolonged antibiotic courses are common in patients with lower
      respiratory tract infections (LRTIs) and contribute to antibiotic resistance and
      side effects. This study describes a multidisciplinary intervention to reduce
      antibiotic duration in LRTI patients. METHODS: This was a prospective before-and
      after intervention study conducted from November 2011 to December 2012.
      Antibiotic duration was recorded for 6 months for all LRTI admissions (pneumonia,
      exacerbation of chronic obstructive pulmonary disease, exacerbation of asthma,
      and other LRTIs), followed by the introduction of an intervention intended to
      reduce the duration of antibiotic treatment. The intervention incorporated an
      antibiotic duration based on the CURB65 score, automatic stop dates and
      pharmacist feedback to prescribers. RESULTS: Two hundred and eighty-one patients
      were included in the pre-intervention group and 221 in the post-intervention
      group. The intervention resulted in a reduction in the duration of antibiotic
      treatment from 8.3 to 6.8 days (P < 0.001, 18.1% relative reduction). The rate of
      antibiotic-related adverse effects reduced from 31% to 19% (P = 0.03, 39.3%
      relative reduction). There was no increase in mortality or length of stay
      CONCLUSIONS: A simple intervention can significantly reduce antibiotic duration
      and antibiotic-related side effects.

PMID- 24022068
TI  - Long-term suppression of HIV-1C virus production in human peripheral blood
      mononuclear cells by LTR heterochromatization with a short double-stranded RNA.
AB  - OBJECTIVES: A region in the conserved 5' long terminal repeat (LTR) promoter of
      the integrated HIV-1C provirus was identified for effective targeting by a short
      double-stranded RNA (dsRNA) to cause heterochromatization leading to a long
      lasting decrease in viral transcription, replication and subsequent productive
      infection in human host cells. METHODS: Small interfering RNAs (siRNAs) were
      transfected into siHa cells containing integrated LTR-luciferase reporter
      constructs and screened for efficiency of inducing transcriptional gene silencing
      (TGS). TGS was assessed by a dual luciferase assay and real-time PCR. Chromatin
      modification at the targeted region was also studied. The efficacy of potent
      siRNA was then checked for effectiveness in TZM-bl cells and human peripheral
      blood mononuclear cells (PBMCs) infected with HIV-1C virus. Viral Gag-p24 antigen
      levels were determined by ELISA. RESULTS: One HIV-1C LTR-specific siRNA
      significantly decreased luciferase activity and its mRNA expression with no such
      effect on HIV-1B LTR. This siRNA-mediated TGS was induced by histone methylation,
      which leads to heterochromatization of the targeted LTR region. The same siRNA
      also substantially suppressed viral replication in TZM-bl cells and human PBMCs
      infected with various HIV-1C clinical isolates for >=3 weeks after a single
      transfection, even of a strain that had a mismatch in the target region.
      CONCLUSIONS: We have identified a potent dsRNA that causes long-term suppression
      of HIV-1C virus production in vitro and ex vivo by heritable epigenetic
      modification at the targeted C-LTR region. This dsRNA has promising therapeutic
      potential in HIV-1C infection, the clade responsible for more than half of AIDS
      cases worldwide.

PMID- 24022069
TI  - Within-lineage variability of ST131 Escherichia coli isolates from humans and
      companion animals in the south of Europe.

PMID- 24022070
TI  - Animal models of sepsis.
AB  - Sepsis remains a common, serious, and heterogeneous clinical entity that is
      difficult to define adequately. Despite its importance as a public health
      problem, efforts to develop and gain regulatory approval for a specific
      therapeutic agent for the adjuvant treatment of sepsis have been remarkably
      unsuccessful. One step in the critical pathway for the development of a new agent
      for adjuvant treatment of sepsis is evaluation in an appropriate animal model of
      the human condition. Unfortunately, the animal models that have been used for
      this purpose have often yielded misleading findings. It is likely that there are
      multiple reasons for the discrepancies between the results obtained in tests of
      pharmacological agents in animal models of sepsis and the outcomes of human
      clinical trials. One of important reason may be that the changes in gene
      expression, which are triggered by trauma or infection, are different in mice, a
      commonly used species for preclinical testing, and humans. Additionally, many
      species, including mice and baboons, are remarkably resistant to the toxic
      effects of bacterial lipopolysaccharide, whereas humans are exquisitely
      sensitive. New approaches toward the use of animals for sepsis research are being
      investigated. But, at present, results from preclinical studies of new
      therapeutic agents for sepsis must be viewed with a degree of skepticism. 

PMID- 24022071
TI  - Human leukocyte antigen-G and regulatory T cells during specific immunotherapy
      for pollen allergy.
AB  - BACKGROUND: TH2-biased immune responses are important in allergy pathogenesis.
      Mechanisms of allergen-specific immunotherapy (SIT) might include the induction
      of regulatory T cells (Tregs) and immunoglobulin (Ig) G4 blocking antibodies, a
      reduction in the number of effector cells, and skewing of the cytokine profile
      towards a TH1-polarized immune response. We investigated the effects of SIT on T
      cells, on immunomodulation of human leukocyte antigen (HLA)-G, which has been
      associated with allergy, on regulatory cytokine expression, and on serum allergen
      specific antibody subclasses (IgE and IgG4). METHODS: Eleven birch and/or grass
      pollen-allergic patients and 10 healthy nonatopic controls were studied before
      and during SIT. Tregs, chemokine receptors, soluble HLA-G (sHLA-G), Ig-like
      transcript (ILT) 2, specific IgE, and IgG4 were studied. Peripheral blood
      mononuclear cells (PBMCs) were stimulated with pollen extract in vitro and immune
      factors were evaluated. RESULTS: During SIT, the main changes in the peripheral
      blood were an increase in CXCR3(+)CD4(+)CD25(+)CD127(low/-) Tregs and a decrease
      in CCR4(+)CD4(+)CD25(+)CD127(low/-) Tregs, an increase in allergen-specific IgG4,
      and a decrease in sHLA-G during the first half of the treatment period. In the
      PBMC in vitro experiments, the following changes were observed upon allergen
      stimulation: an increase in CD4(+)CD25(+)CD127(low/-) Tregs and
      ILT2(+)CD4(+)CD25(+)CD127(low/-) Tregs, an increase in IL-10 and IL-2 levels, and
      an increase in sHLA-G that was most pronounced at the start of SIT. CONCLUSIONS:
      The changes in CXCR3(+)CD4(+)CD25(+)CD127(low/-) Treg, IgG4, and sHLA-G levels in
      the peripheral blood and in ILT2(+) Treg, IL-10, IL-2, and sHLA-G levels upon in
      vitro allergen stimulation suggest an upregulation in immunomodulatory factors
      and, to some degree, a shift towards TH1 during SIT.

PMID- 24022073
TI  - Stability and fitness impact of the visually discernible Rosea1 marker in the
      Tobacco etch virus genome.
AB  - Antirrhinum majus Rosea1 (Ros1) is an MYB-related transcription factor that
      induces anthocyanin biosynthesis in plant tissues, and has been shown to be
      suitable for visual tracking of virus infection in plants. However, activation of
      anthocyanin biosynthesis has far reaching effects on plant physiology and could
      consequently have negative effects on viral replication. Therefore, viruses
      carrying the Ros1 marker might have a low fitness and consequently rapidly lose
      the marker. To compare the stability of the Ros1 marker, we generated Tobacco
      etch virus (TEV) based constructs containing either Ros1 or the enhanced green
      fluorescent protein (eGFP) between the NIb and CP cistrons (TEV-Ros1 and TEV
      eGFP, respectively). We measured the within-host competitive fitness of both
      viruses by direct competitions with a common competitor during infection of
      Nicotiana tabacum. The fitness of TEV-Ros1 was significantly lower than that of
      TEV-eGFP, and both recombinant viruses had a significantly lower fitness than the
      wild-type virus. Nevertheless, after seven weeks of infection in N. tabacum,
      similar levels of marker gene instability where found for both viruses. Despite
      lower fitness of the marked virus, Ros1 is therefore a viable alternative marker
      for tracking viral infection in plants. 

PMID- 24022072
TI  - Movements of wild ruddy shelducks in the Central Asian Flyway and their spatial
      relationship to outbreaks of highly pathogenic avian influenza H5N1.
AB  - Highly pathogenic avian influenza H5N1 remains a serious concern for both poultry
      and human health. Wild waterfowl are considered to be the reservoir for low
      pathogenic avian influenza viruses; however, relatively little is known about
      their movement ecology in regions where HPAI H5N1 outbreaks regularly occur. We
      studied movements of the ruddy shelduck (Tadorna ferruginea), a wild migratory
      waterfowl species that was infected in the 2005 Qinghai Lake outbreak. We defined
      their migration with Brownian Bridge utilization distribution models and their
      breeding and wintering grounds with fixed kernel home ranges. We correlated their
      movements with HPAI H5N1 outbreaks, poultry density, land cover, and latitude in
      the Central Asian Flyway. Our Akaike Information Criterion analysis indicated
      that outbreaks were correlated with land cover, latitude, and poultry density.
      Although shelduck movements were included in the top two models, they were not a
      top parameter selected in AICc stepwise regression results. However, timing of
      outbreaks suggested that outbreaks in the flyway began during the winter in
      poultry with spillover to wild birds during the spring migration. Thus, studies
      of the movement ecology of wild birds in areas with persistent HPAI H5N1
      outbreaks may contribute to understanding their role in transmission of this
      disease. 

PMID- 24022075
TI  - Characterization of a novel humanized anti-CD20 antibody with potent anti-tumor
      activity against non-Hodgkin's lymphoma.
AB  - BACKGROUND: Rituximab, a mouse Fab and human Fc chimeric antibody, has been
      widely used to treat Non-Hodgkin's lymphoma (NHL). However, only 48% of patients
      respond to the treatment and complete response rate is below 10%. Also,
      immunogenicity was reported in 17-20% patients receiving the treatment, making it
      unsuitable for long term diseases such as autoimmune disorders. It has been a hot
      research field to "humanize" rituximab toward improved efficacy and reduced
      immunogenicity. METHODS: In this study, an advanced antibody humanization
      technology was applied to the sequence of the anti-CD20 antibody 2B8, its
      sequence of which was based on the original murine monoclonal antibody of
      rituximab in Roche. The complementarity-determining regions (CDRs) of the
      humanized antibodies were further optimized through computer-aided molecular
      dock. RESULTS: Five novel humanized anti-CD20 antibodies 1-5(1635, 1534, 3637,
      1634 and 1536) were generated and their immunogenicity was significantly
      decreased when compared to rituximab. The novel humanized anti-CD20 antibodies 1
      5 retained the binding activity of their murine counterpart, as demonstrated by
      the fluorescence-activated cell-sorting analysis (FACS). When compared to
      rituximab, the humanized antibodies still have the similar properties on both
      complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated
      cytotoxicity (ADCC). Furthermore, its anti-tumor efficacy in xenograft model is
      comparable to that of rituximab. CONCLUSION: The humanized anti-CD20 antibodies 1
      5 have lower immunogenicity than rituximab. And at the same time, they still
      retain the anti-tumor effect both in vitro and vivo.

PMID- 24022074
TI  - Effect of proinflammatory gene polymorphisms on the risk of Alzheimer's disease.
AB  - BACKGROUND: A number of studies associate Alzheimer's disease (AD) with APOE
      polymorphism and alleles which favor the increased expression of immunological
      mediators such as cytokines or acute-phase proteins. OBJECTIVE: In this study we
      evaluated the distribution of a set of functionally important polymorphisms of
      genes encoding prototypical inflammatory molecules in individuals with AD. We
      also investigated whether a synergistic effect of these proinflammatory gene
      polymorphisms on the risk of AD could be hypothesized. METHODS: In a genetic
      association study that included 533 AD patients and 713 controls, the following
      gene polymorphisms were analyzed: C-reactive protein (CRP) 1059 G/C, interleukin
      6 (IL6) -174 G/C, interleukin 1beta (IL1B) -31 T/C, tumor necrosis factor alpha
      (TNF-alpha) -308 G/A, macrophage migration inhibitory factor (MIF) -173 G/C,
      monocyte chemoattractant protein 1 (CCL2) -2518 A/G, intercellular adhesion
      molecule 1 (ICAM1) 469 E/K, E-selectin (SELE) Ser128Arg, macrophage inflammatory
      protein 1alpha (CCL3) -906 T/A, matrix metalloproteinase 3 (MMP3) -1171 5A/6A and
      matrix metalloproteinase 9 (MMP9) -1562 C/T. RESULTS: We found that IL6, IL1B,
      CCL2, CCL3, SELE, ICAM1, MMP3, and MMP9 gene polymorphisms were significantly and
      independently associated with AD. The association remained significant even after
      the Bonferroni correction. We also found that these proinflammatory polymorphisms
      were associated with different levels of risk for AD, depending on the number of
      high-risk genotypes concomitantly carried by a given individual. CONCLUSION:
      Proinflammatory genotypes might influence the development and progression of AD
      exerting a potential synergistic effect.

PMID- 24022076
TI  - Keeping you up at night.

PMID- 24022077
TI  - Hospital nursing and 30-day readmissions among Medicare patients with heart
      failure, acute myocardial infarction, and pneumonia.

PMID- 24022078
TI  - The diffusion of Magnet hospital recognition.

PMID- 24022079
TI  - The value of Magnet(r).

PMID- 24022080
TI  - National survey of hospital nursing research, part 1. Research requirements and
      outcomes.

PMID- 24022081
TI  - National survey of hospital nursing research, part 2. Facilitators and
      hindrances.

PMID- 24022082
TI  - Lower mortality in Magnet hospitals.

PMID- 24022083
TI  - Creative approaches to increasing hospital-based nursing research.

PMID- 24022084
TI  - Using the Agency for Healthcare Research and Quality patient safety indicators
      for targeting nursing quality improvement.

PMID- 24022085
TI  - Facile and efficient KOH-catalysed reduction of esters and tertiary amides.
AB  - Esters and tertiary amides were efficiently reduced to their corresponding
      alcohols and amines in high yields under mild and environmentally friendly
      conditions. The presented KOH-catalysed system involves a simple hydrosilylation
      procedure that is carried out under solvent-free conditions and does not require
      the use of inert conditions. 

PMID- 24022086
TI  - Responsiveness of neoadjuvant chemotherapy before surgery predicts favorable
      prognosis for cervical cancer patients: a meta-analysis.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) before surgery has already shown the
      therapy effectiveness inpatients with cervical cancer. The present meta-analysis
      was conducted to determine whether the response to NAC predicts for prognosis.
      METHODS: Systematic computerized searches of the Pub-Med and Web of Knowledge
      were performed. Prognosis outcomes included progression-free survival (PFS), and
      overall survival (OS). The pooled odd ratio (OR) was estimated by using fixed
      effect model or random-effect model according to heterogeneity between studies.
      RESULTS: Eighteen studies with 1,785 patients were included. Cisplatin-based NAC
      treatments were most commonly used. The clinical response rate ranged from 48.4
      to 93.0 %, and the pathological response rate ranged from 27.6 to 30.6 %. The
      pooled ORs estimating the association of PFS with NAC response were 5.707 (95 %
      CI3.564-9.137), 6.798 (95 % CI 4.716-9.799), 6.327 (95 %CI 4.398-9.102), and
      5.214 (95 % CI 3.748-7.253) at 1-,2-, 3-, and 5-year follow-up, respectively, and
      the pooled ORs estimating the association of OS with NAC response were 6.179 (95
      % CI 3.390-11.264), 9.155 (95 % CI5.759-14.555), 8.431 (95 % CI 5.667-12.543),
      and 5.785(95 % CI 4.124-8.115) at 1-, 2-, 3-, and 5-year follow-up,respectively.
      No obvious statistical heterogeneity was detected. Funnel plots and Egger's tests
      did not reveal publication bias. Sensitivity analysis showed the results of meta
      analysis were robust. CONCLUSION: This meta-analysis confirms that response to
      NAC is an indicator for PFS and OS, and suggests that patients-achieving response
      of NAC before surgery predicts favorable prognosis for cervical cancer patients.

PMID- 24022087
TI  - Peritoneal metastases of lower gastrointestinal tract origin: a comparative study
      of patient outcomes following cytoreduction and intraperitoneal chemotherapy.
AB  - BACKGROUND: Cytoreductive surgery (CS) combined with intraperitoneal chemotherapy
      (IPC) is a multimodal approach to the treatment of peritoneal metastases (PM) of
      lower gastrointestinal origin. This study examines patient outcomes and
      critically evaluates its patterns of recurrences relative to the site of
      metastatic origin. METHODS: Patients treated with CS/IPC from 2000 to 2012 where
      PM arose from a primary tumour of the appendix, colon and rectum were identified
      from a prospective database for retrospective evaluation. The primary end points
      were survival (overall and disease-free), and secondary end points include
      patterns of recurrence and prognostic factors associated with overall outcomes.
      RESULTS: Two hundred and eleven patients were followed up for a median of 23.3
      months (range 1-156). Overall median survival was 46.8 months, and the 1-, 3-, 5
      year survival rates were 87, 56 and 42 %, respectively. The 5-year survival of
      patients with appendiceal, colonic and rectal PM was 55, 33 and 20 %,
      respectively. Tumour origin was the only independent prognostic factor associated
      with overall survival (p = 0.03). Recurrences were more common in patients of
      colorectal origin over appendiceal origin (p < 0.001) and were more likely to be
      of a systemic nature (p = 0.05). CONCLUSION: CS/IPC provides an option for
      improved survival in patients with PM of lower gastrointestinal origin and
      appears to be most promising in patients with disease of appendiceal origin.

PMID- 24022088
TI  - Epidermal growth factor receptor subunit locations determined in hydrated cells
      with environmental scanning electron microscopy.
AB  - Imaging single epidermal growth factor receptors (EGFR) in intact cells is
      presently limited by the available microscopy methods. Environmental scanning
      electron microscopy (ESEM) of whole cells in hydrated state in combination with
      specific labeling with gold nanoparticles was used to localize activated EGFRs in
      the plasma membranes of COS7 and A549 cells. The use of a scanning transmission
      electron microscopy (STEM) detector yielded a spatial resolution of 3 nm,
      sufficient to identify the locations of individual EGFR dimer subunits. The sizes
      and distribution of dimers and higher order clusters of EGFRs were determined.
      The distance between labels bound to dimers amounted to 19 nm, consistent with a
      molecular model. A fraction of the EGFRs was found in higher order clusters with
      sizes ranging from 32-56 nm. ESEM can be used for quantitative whole cell
      screening studies of membrane receptors, and for the study of nanoparticle-cell
      interactions in general. 

PMID- 24022089
TI  - Intravital microscopy for imaging subcellular structures in live mice expressing
      fluorescent proteins.
AB  - Here we describe a procedure to image subcellular structures in live rodents that
      is based on the use of confocal intravital microscopy. As a model organ, we use
      the salivary glands of live mice since they provide several advantages. First,
      they can be easily exposed to enable access to the optics, and stabilized to
      facilitate the reduction of the motion artifacts due to heartbeat and
      respiration. This significantly facilitates imaging and tracking small
      subcellular structures. Second, most of the cell populations of the salivary
      glands are accessible from the surface of the organ. This permits the use of
      confocal microscopy that has a higher spatial resolution than other techniques
      that have been used for in vivo imaging, such as two-photon microscopy. Finally,
      salivary glands can be easily manipulated pharmacologically and genetically, thus
      providing a robust system to investigate biological processes at a molecular
      level. In this study we focus on a protocol designed to follow the kinetics of
      the exocytosis of secretory granules in acinar cells and the dynamics of the
      apical plasma membrane where the secretory granules fuse upon stimulation of the
      beta-adrenergic receptors. Specifically, we used a transgenic mouse that co
      expresses cytosolic GFP and a membrane-targeted peptide fused with the
      fluorescent protein tandem-Tomato. However, the procedures that we used to
      stabilize and image the salivary glands can be extended to other mouse models and
      coupled to other approaches to label in vivo cellular components, enabling the
      visualization of various subcellular structures, such as endosomes, lysosomes,
      mitochondria, and the actin cytoskeleton. 

PMID- 24022090
TI  - Development and validation of a scoring system to identify individuals at high
      risk for advanced colorectal neoplasms who should undergo colonoscopy screening.
AB  - BACKGROUND & AIMS: Screening the population for colorectal cancer (CRC) by
      colonoscopy could reduce the disease burden. However, targeted screening of
      individuals at high risk could increase its cost effectiveness. METHODS: We
      developed a scoring system to identify individuals with at least 1 advanced
      adenoma, based on easy-to-collect risk factors among 7891 participants of the
      German screening colonoscopy program. The system was validated in an independent
      sample of 3519 participants. Multiple logistic regression was used to develop the
      algorithm, and the regression coefficient-based scores were used to determine
      individual risks. Relative risk and numbers of colonoscopies needed for detecting
      one or more advanced neoplasm(s) were calculated for quintiles of the risk score.
      The predictive ability of the scoring system was quantified by the area under the
      curve. RESULTS: We identified 9 risk factors (sex, age, first-degree relatives
      with a history of CRC, cigarette smoking, alcohol consumption, red meat
      consumption, ever regular use [at least 2 times/wk for at least 1 y] of
      nonsteroidal anti-inflammatory drugs, previous colonoscopy, and previous
      detection of polyps) that were associated significantly with risk of advanced
      neoplasms. The developed score was associated strongly with the presence of
      advanced neoplasms. In the validation sample, individuals in the highest quintile
      of scores had a relative risk for advanced neoplasm of 3.86 (95% confidence
      interval, 2.71-5.49), compared with individuals in the lowest quintile. The
      number needed to screen to detect 1 or more advanced neoplasm(s) varied from 20
      to 5 between quintiles of the risk score. In the validation sample, the scoring
      system identified patients with CRC or any advanced neoplasm with area under the
      curve values of 0.68 and 0.66, respectively. CONCLUSIONS: We developed a scoring
      system, based on easy-to-collect risk factors, to identify individuals most
      likely to have advanced neoplasms. This system might be used to stratify
      individuals for CRC screening.

PMID- 24022091
TI  - Food insecurity and antiretroviral adherence among HIV positive adults who drink
      alcohol.
AB  - Food insecurity is associated with HIV treatment non-adherence and poor health
      outcomes for people living with HIV/AIDS. Given the poor nutritional status
      common to people who drink alcohol, food insecurity may be particularly
      problematic for HIV positive individuals who drink alcohol. To examine food
      insecurity among HIV positive men and women who drink alcohol and its association
      with antiretroviral therapy (ART) adherence, health outcomes and health service
      utilization. Adults living with HIV (N = 183) in Atlanta, Georgia who reported
      alcohol use in the previous week and were receiving ART participated in a 12
      month cohort. Participants were recruited from infectious disease clinics and
      social services to complete computerized interviews, monthly-unannounced pill
      counts to monitor ART adherence, and daily cell-phone delivered interactive-text
      assessments for alcohol use. Forty-three percent of participants experienced food
      insecurity during at least one month of the study period. Food insecurity was
      independently associated with suboptimal ART adherence and less suppressed HIV
      viral load over. Individuals who experienced food insecurity also had histories
      of more medical and psychiatric hospitalizations, and greater mental health
      problems. Food insecurity is prevalent among alcohol using people receiving ART
      and food insecurity is associated with treatment non-adherence, poor health
      outcomes, and increased medical and psychiatric hospitalizations.

PMID- 24022093
TI  - Application of new photolabile protecting groups as photocleavable joints of
      block copolymers.
AB  - New photoresponsive block copolymers (BCPs) have been developed by incorporating
      photocleavable units. These photocleavable units are derived from robust
      photolabile protecting groups (PPGs); UV irradiation cleaves the BCPs and
      releases a well-defined chemically active functional group at the cleaved end of
      a PS polymer. 

PMID- 24022092
TI  - Covalent modification of cell surfaces with TLR agonists improves & directs
      immune stimulation.
AB  - We present a primary example of a cell surface modified with a synergistic
      combination of agonists to tune immune stimulation. A model cell line, Lewis Lung
      Carcinoma, was covalently modified with CpG-oligonucleotides and lipoteichoic
      acid, both Toll-like receptor (TLR) agonists. The immune-stimulating constructs
      provided greater stimulation of NF-kappaB in a model cell line and bone marrow
      derived dendritic cells than the components unconjugated in solution. 

PMID- 24022094
TI  - Peginterferon plus Chinese herbal therapy is associated with a higher virological
      response than only peginterferon therapy in chronic hepatitis C.
AB  - Traditional Chinese herbal therapies are widely used for the treatment of chronic
      hepatitis C (CHC) in China and several Asian countries. The aim of this study was
      to perform a meta-analysis of randomized controlled trials (RCTs) comparing
      peginterferon therapy with peginterferon plus Chinese herbal therapy for the
      treatment of CHC. The Cochrane Central Register of Controlled Trials, Medline,
      Science Citation Index, EMBASE, China National Knowledge Infrastructure, Wanfang
      Database, and China Biomedical Database were searched to identify RCTs that
      evaluated the virological response of CHC patients to peginterferon therapy and
      peginterferon plus Chinese herbal therapy. We statistically combined data using a
      fixed-effects meta-analysis according to the intention-to-treat principle. The
      literature search yielded 905 studies and nine RCTs composed of 858 patients
      matched the selection criteria. Overall, sustained virological response (SVR) was
      significantly higher in patients treated with peginterferon plus Chinese herbs
      than in patients treated with peginterferon alone (81 % vs. 64 %, respectively;
      odds ratio, 2.60; 95 % confidence interval: 1.32-5.14; p < 0.05). A combined
      therapy of peginterferon plus Chinese herbs was also superior to peginterferon
      therapy in achieving an early viral response (EVR, 80 % vs. 70 %, respectively),
      a viral response at week 24 of treatment (82 % vs. 73 %, respectively), and end
      of-treatment viral response (ETVR, 73 % vs. 62 %, respectively). The combined
      therapy resulted in fewer relapses, fewer adverse events, and more rapid alanine
      transaminase normalization; however, both treatments yielded a similar rapid
      viral response (RVR, 53 % vs. 57 %, respectively). The current evidence suggests
      that combined therapy of peginterferon plus Chinese herbs yields a higher viral
      response and results in fewer relapses and fewer adverse events than
      peginterferon therapy alone.

PMID- 24022096
TI  - ?

PMID- 24022097
TI  - Development of freshwater sediment management standards for organic matters,
      nutrients, and metals in Korea.
AB  - Korean water quality managers are required to promptly develop national
      assessment standards for freshwater sediment quality due to the Four Major River
      Restoration Project in Korea in 2009. We conducted this study to develop sediment
      management standards (SMSs), determining obviously and severely polluted
      sediment, which could have adverse impacts on water quality and aquatic
      ecosystem. The SMSs values were derived from the 95th percentile of concentration
      distribution for organic matter and nutrients in sediment quality database. For
      the SMSs of metals, foreign sediment quality guidelines (SQGs) were adopted. As a
      result, 13% for loss on ignition (LOI), 1,600 mg/kg for total phosphorus (TP),
      and 5,600 mg/kg for total nitrogen (TN) were set as the SMSs for freshwater
      sediment in Korea. These values were higher than the range of heavily polluted
      sediment from USEPA Region 5 guideline derived by the similar approaches for the
      Great Lakes harbor sediments, and similar or lower than the severe effect level
      (SEL) from provincial sediment quality guideline (PSQG) of Ontario, Canada by
      screening level concentration (SLC) approach. However, SMSs in the present study
      are appropriate considering the concentration ranges and the Korean SMSs'
      definition for freshwater sediments in Korea. The Puget Sound marine sediment
      cleanup screening level (CSL) in Washington State, USA were adopted as the Korean
      SMSs for As (93 mg/kg), Cd (6.7 mg/kg), Cr (270 mg/kg), Cu (390 mg/kg), Pb (530
      mg/kg), and Zn (960 mg/kg) in freshwater sediments. Hg concentration (0.59 mg/kg)
      of CSL was too low to determine the polluted freshwater sediments in Korea, and
      the SEL of Ontario, Canada for mercury concentration (2 mg/kg) was selected as
      the SMS for Hg. These values were found reasonable through the assessment of
      applicability with the datasets from locations directly affected by obvious point
      sources. These results indicate that SMSs for organic matter, nutrient, and
      metals derived within the present study can successfully determine obviously and
      severely polluted sediment in Korea. However, the SMSs have limits to
      specifically determine the effects of polluted sediment on water quality and
      aquatic ecosystem in Korea. Thus, we will revise and specify SMSs considering
      those effects and further sediment quality assessment framework in the near
      future.

PMID- 24022099
TI  - Should apple snail Pomacea canaliculata (Caenogastropoda, Ampullariidae) be used
      as bioindicator for BDE-209?
AB  - Apple snail Pomacea canaliculata has been reported to accumulate polybrominated
      diphenyl ethers (PBDEs) and was recently proposed as PBDE bioindicator. This work
      investigates the ability of P. canaliculata to accumulate BDE-209 by dietary
      exposure under controlled experimental conditions. A 30-day long enrichment
      feeding assay was carried out using 30 adult apple snails, placed in individual
      aquaria. Food was enriched at three BDE-209 concentrations (400, 4,700, and 8,300
      MUg g(-1) lipid weight). Correlation between BDE-209 values in food and snail
      tissue were estimated according to Stockholm Convention suggested criteria for
      chemicals with K(OW) >5. All animals survived with no evident physical
      alterations, and all of them accumulated BDE-209. BDE-209 levels in tissue
      samples increased exponentially with the exposure concentration. The
      bioaccumulation factor vs. food concentration plot showed a peculiar pattern, in
      which at intermediate concentrations the snails accumulated less BDE-209 than
      expected. Our results suggest that P. canaliculata would present a detoxification
      mechanism for BDE-209 different from the most commonly reported metabolic
      pathways.

PMID- 24022098
TI  - Risk of laryngeal and nasopharyngeal cancer associated with arsenic and cadmium
      in the Tunisian population.
AB  - Chronic exposure to heavy metals has long been recognized as being capable of
      increasing head and neck cancer (HNC) incidence, such as laryngeal (LC) and
      nasopharyngeal (NPC), among exposed human populations. The aim of the present
      study was to evaluate the concentrations of arsenic (As) and cadmium (Cd) in the
      blood of 145 patients (LC and NPC) and 351 controls in order to establish a
      potential relationship between these factors and the occurrence of LC and NPC.
      Mean blood levels of As and Cd in patients (5.67 and 3.51 MUg/L, respectively)
      were significantly higher than those of controls (1.57 and 0.74 MUg/L,
      respectively). The blood levels of As and Cd were mostly significantly higher
      than those of controls (p<0.05) after controlling the other risk factors of HNC
      including tobacco smoking and chewing, and alcohol drinking. Cd levels in blood
      increase significantly with the number of occupational exposure years for
      patients (p<0.05). However, seafood was not found to be contributing as an
      exposure source. Among these risk factors, smoking (>30 pack years) and
      occupational exposure (>20 years) presented the most significant association with
      HNC (OR=10.22 and 10.38, respectively, p<0.001). Cd level in blood sample of
      cases that are occupationally exposed/tobacco users (smokers and chewers) were
      higher than that of non-occupationally exposed/nontobacco users (p<0.001). The
      logistic regression model illustrated that HNC (LC+NPC) was significantly
      associated with blood levels of As (OR=2.41, p<0.001) and Cd (OR=4.95, p<0.001).

PMID- 24022100
TI  - Comparative study of adsorption of Pb(II) on native garlic peel and mercerized
      garlic peel.
AB  - A comparative study using native garlic peel and mercerized garlic peel as
      adsorbents for the removal of Pb(2+) has been proposed. Under the optimized pH,
      contact time, and adsorbent dosage, the adsorption capacity of garlic peel after
      mercerization was increased 2.1 times and up to 109.05 mg g(-1). The equilibrium
      sorption data for both garlic peels fitted well with Langmuir adsorption
      isotherm, and the adsorbent-adsorbate kinetics followed pseudo-second-order
      model. These both garlic peels were characterized by elemental analysis, Fourier
      transform infrared spectrometry (FT-IR), and scanning electron microscopy, and
      the results indicated that mercerized garlic peel offers more little pores acted
      as adsorption sites than native garlic peel and has lower polymerization and
      crystalline and more accessible functional hydroxyl groups, which resulted in
      higher adsorption capacity than native garlic peel. The FT-IR and X-ray
      photoelectron spectroscopy analyses of both garlic peels before and after loaded
      with Pb(2+) further illustrated that lead was adsorbed on the through chelation
      between Pb(2+) and O atom existed on the surface of garlic peels. These results
      described above showed that garlic peel after mercerization can be a more
      attractive adsorbent due to its faster sorption uptake and higher capacity.

PMID- 24022101
TI  - Source apportionment of the carcinogenic potential of polycyclic aromatic
      hydrocarbons (PAH) associated to airborne PM10 by a PMF model.
AB  - In order to perform a study of the carcinogenic potential of polycyclic aromatic
      hydrocarbons (PAH), benzo(a)pyrene equivalent (BaP-eq) concentration was
      calculated and modelled by a receptor model based on positive matrix
      factorization (PMF). Nineteen PAH associated to airborne PM10 of Zaragoza, Spain,
      were quantified during the sampling period 2001-2009 and used as potential
      variables by the PMF model. Afterwards, multiple linear regression analysis was
      used to quantify the potential sources of BaP-eq. Five sources were obtained as
      the optimal solution and vehicular emission was identified as the main
      carcinogenic source (35 %) followed by heavy-duty vehicles (28 %), light-oil
      combustion (18 %), natural gas (10 %) and coal combustion (9 %). Two of the most
      prevailing directions contributing to this carcinogenic character were the NE and
      N directions associated with a highway, industrial parks and a paper factory. The
      lifetime lung cancer risk exceeded the unit risk of 8.7 x 10(-5) per ng/m(3) BaP
      in both winter and autumn seasons and the most contributing source was the
      vehicular emission factor becoming an important issue in control strategies.

PMID- 24022102
TI  - Organophosphate pesticide exposure and child health in China.
AB  - Currently, organophosphate pesticides (OPs) are widely used for agriculture in
      China and around the world. A few epidemiological studies have examined the
      association between exposure to OPs and children's health, but these studies
      reported inconsistent results. In view of the limitations of testing techniques
      and the intrinsic incompleteness of scientific evidence from current studies, we
      have considered some issues which may be interpreted and handled with caution.

PMID- 24022103
TI  - Enhanced adsorptive removal of naphthalene intermediates from aqueous solution by
      introducing reed straw into sewage sludge-based activated carbon.
AB  - The disposal of sewage sludge (SS) and reed straw (RS) has becoming a critical
      issue due to their rapid production. In this study, the SS-based activated carbon
      (SSC) was produced by introducing the RS as a component material. Properties
      including BET surface area, pore volume, surface chemical groups, and
      morphologies were characterized. The adsorption of 1-diazo-2-naphthol-4-sulfonic
      acid (1,2,4-Acid) and 2-Naphthol (2-Nap), which differs in their physicochemical
      properties, on as-prepared carbons were investigated. The overall adsorption was
      found to be jointly controlled by external mass transfer and intraparticle
      diffusion, and the optimal pH was found to be 5 due to their electrostatic
      attraction. Further study revealed that the SS- and RS-based carbons (SC and RSC,
      respectively) exhibited different adsorption behavior toward 1,2,4-Acid and 2
      Nap. The calculated adsorption capacity from Langmuir-Freundlich model of SC and
      RSC for the two intermediates was 141.0, 84.6 mg g(-1) and 48.2, 110.2 mg g(-1),
      respectively, whereas their hybrid product (SSC) showed comparable capacity for
      1,2,4-Acid (117.8 mg g(-1)), as well as higher capacity for 2-Nap (157.5 mg g-1).
      It was found that the presence of meso- or macropores facilitates the
      precipitation of mineral phases of inorganic substances during carbonization,
      attracting the molecules with polar functional groups, while the introduction of
      C-rich RS to SS enhances the adsorption of hydrophobic molecules

PMID- 24022108
TI  - Role of hMLH1 and E-cadherin promoter methylation in gastric cancer progression.
AB  - INTRODUCTION: Gastric cancer (GC) is one of the leading causes of cancer-related
      death in Iran. Genome stability is one of the main genetic issues in cancer
      biology which is governed via the different repair systems such as DNA mismatch
      repair (MMR). A clear correlation between MMR defects and tumor progression has
      been shown. Beside the genetic mutations, epigenetic changes also have a
      noticeable role in MMR defects. METHODS: Here, we assessed promoter methylation
      status and the level of hMLH1mRNA expression as the main component of MMR system
      in 51 GC patients using the methylation-specific PCR and real-time PCR,
      respectively. Moreover, we performed a promoter methylation study of the E
      cadherin gene promoter. RESULTS: It was observed that, 12 out of 39 cases (23.5%)
      had hMLH1 overexpression. Hypermethylation of hMLH1 and E-cadherin promoter
      regions were observed in 25.5 and 36.4%, respectively. Although, there was no
      significant correlation between hMLH1 mRNA expression and clinicopathological
      features, there are significant correlations between E-cadherin promoter
      methylation and tumor stage (p = 0.028) and location (p = 0.025). The rate of
      hMLH1 promoter methylation in this study was lower than that in the other
      population, showing the importance of the other mechanisms, in gastric
      tumorigenesis. CONCLUSION: The results of this study indicate that DNA repair
      system is adversely affected by hypermethylation of hMLH1 in a fraction of
      gastric cancer patients. Additionally, E-cadherin hypermethylation seen in a
      subset of our gastric cancer patients is consistent with other reports showing
      correlation with aggressiveness and metastasis of gastric cancer.

PMID- 24022109
TI  - Variations of IGHMBP2 gene was not the major cause of Han Chinese patients with
      non-5q-spinal muscular atrophies.
AB  - Spinal muscular atrophy with respiratory distress type 1 (SMARD1), a notably
      common form of non-5q-spinal muscular atrophy, can be confused with infantile
      spinal muscular atrophy and is characterized by the early onset of diaphragmatic
      palsy and predominantly distal muscle weakness. The defective gene,
      immunoglobulin mu-binding protein 2 (IGHMBP2), is located on chromosome 11q13
      q21. In this study, we screened the IGHMBP2 gene in 53 unrelated Han Chinese non
      5q-spinal muscular atrophy patients and 100 healthy controls. Two novel mutations
      (c.711+1G>C and c.1817G>A) and 5 nucleotide polymorphisms (c.57T>C, c.1554C>T,
      c.1914G>A, c.2080C>T, and c.2270G>C) were identified. However, only 1 patient
      harbored the compound heterozygous mutations (c.711+1G>C, c.1817G>A).
      Furthermore, the homozygous c.2636C>A (p.T879 K) variation, which has been
      included as a mutation in the Human Gene Mutation Database, was found both in
      patients and healthy individuals. In conclusion, the IGHMBP2 gene was not found
      to be a major causative gene linked to Han Chinese non-5q-spinal muscular atrophy
      patients. 

PMID- 24022110
TI  - Children with central and peripheral neurologic disorders have distinguishable
      patterns of dysphagia on videofluoroscopic swallow study.
AB  - To determine whether findings on videofluoroscopic swallow studies reveal
      different patterns of dysphagia between children with central and peripheral
      neurologic disorders, a retrospective study of 118 videofluoroscopic swallow
      studies was completed. There were 3 groups: cerebral palsy with only spastic
      features (n = 53), cerebral palsy with dyskinetic features (n = 34), and
      neuromuscular disorders (myotonic dystrophy I, n = 5; spinal muscular atrophy I
      II, n = 8; Duchenne muscular dystrophy, n = 8; other neuromuscular disorder, n =
      10). Interpretation of the videofluoroscopic swallow studies was not blinded. The
      video fluoroscopic swallow study findings were compared dichotomously between the
      groups. Children with cerebral palsy demonstrated dysphagia in 1 or all phases of
      swallowing. In neuromuscular disorder, muscle weakness results in pharyngeal
      residue after swallow. The underlying swallowing problem in neuromuscular
      disorder is muscle weakness whereas that in cerebral palsy is more complex,
      having to do with abnormal control of swallowing. This study serves as a first
      exploration on specific characteristics of swallowing in different neurologic
      conditions and will help clinicians anticipate what they might expect. 

PMID- 24022111
TI  - Insights on the effects of patient perceptions and awareness on ambulance usage
      in Karachi, Pakistan.
AB  - BACKGROUND: Prehospital care is a vital part of emergency medical care. Countries
      with decentralised ambulance systems, such as Pakistan, require patient knowledge
      as to when to call an ambulance and which service to call. Little is known about
      how patient perceptions of ambulance services affect ambulance usage in most low-
      and middle-income countries (LMIC). The purpose of our study was to analyse
      patient perspectives of the ambulance system in Karachi to understand how to
      improve ambulance use. METHODS: Indepth interviews were conducted with 30
      individuals selected by convenience sampling representing patients who came to
      the emergency department by private transport versus one of two of the main
      ambulance service providers in Karachi. RESULTS: Similar to what has been shown
      in some LMIC contexts, two of the major themes that emerged which affect patient
      decision making with regard to ambulance use were a mistrust of the ambulance
      system or providers and a sense of inadequacy of the local system as compared
      with international standards. In addition, which has not been shown in previous
      studies, there was a fundamental misunderstanding of the role of ambulance
      services in the healthcare infrastructure. CONCLUSIONS: Insight into the main
      issues affecting patient decisions to use an ambulance service offers possible
      targets for patient education that could result in an increase in the proper
      usage of ambulances and thus optimise outcomes from serious injury and illness in
      an LMIC context.

PMID- 24022113
TI  - Biliary complications after liver transplantation: The role of MR imaging using
      different hydrographic sequences in patients with biliary-enteric and duct-to
      duct biliary anastomosis.
AB  - BACKGROUND: To aim of this study was to assess the diagnostic performance of the
      state-of-the-art magnetic resonance cholangiography (MRC) comprising several 2D
      and 3D hydrographic sequences in patients after liver transplantation with
      biliary-enteric and duct-to-duct biliary anastomosis. MATERIAL AND METHODS:
      Retrospective analysis included MRC examinations of 42 patients (21 men, 21
      women) performed from 18 days to 86 months (average, 18.9 months) after liver
      transplantation. Studies were carried out on 1.5 T units, using 4 hydrographic
      (turbo spin echo, TSE) sequences. The analysis included accuracy of MRC in
      detecting biliary complications, as well as frequency of specific complications
      in patients with biliary-enteric anastomosis (n=15) and duct-to-duct biliary
      anastomosis (n=27). In 34 patients the results were correlated with endoscopic
      retrograde cholangiopancreatography ERCP (n=9), ERCP and CT (n=5), ERCP and
      percutaneous cholangiography (n=2), ERCP and T-tube cholangiography (n=1), ERCP,
      PTC, and histopathology (n=1), PTC (n=1), PTC and CT (n=1), PTC and
      histopathology (n=1), T-tube cholangiography (n=4), T-tube cholangiography and CT
      (n=1), fistulography (n=1), CT (n=4), and histopathology (n=3). In the remaining
      8 patients other imaging studies (US, CT, follow-up MRC), laboratory liver
      function tests, and clinical status were the standard of reference. Results MRC
      yielded 94.6% sensitivity in detecting biliary complications in patients after
      liver transplantation. In patients with biliary-enteric anastomosis, disseminated
      biliary strictures were more frequent than in patients with duct-to-duct biliary
      anastomosis (20% vs. 7%). Less frequently, the biliary-enteric anastomosis was
      accompanied by anastomotic strictures (40% vs. 56%) and the presence of
      stones/sludge (20% vs. 37%), but the differences did not show statistical
      significance. CONCLUSIONS: MRC allowed accurate diagnosis of biliary
      complications in patients after liver transplantation and therefore can be used
      as a safe alternative to invasive diagnostic procedures such as ERCP and PTC,
      especially in patients with biliary-enteric anastomosis, in which invasive
      diagnostic procedures are technically challenging. The main limitation of MR
      hydrography is its low accuracy in distinguishing bilomas from other fluid
      collections.

PMID- 24022112
TI  - Real time shift reporting by emergency physicians predicts overall ED
      performance.
AB  - OBJECTIVE: To investigate factors associated with emergency physician perception
      of the shift and to determine whether these perceptions were predictors of
      overall daily emergency department (ED) performance indicators. METHODS: This was
      an observational study conducted at an inner city ED in New South Wales. Shift
      reports completed by the emergency physician in charge at clinical handover times
      between February and July 2012 were included. Variables collected by the shift
      report included (1) total number of patients in ED, (2) number of patients in the
      ED with length of stay (LOS) greater than 4 h, (3) number of admitted patients,
      (4) number of patients waiting to be seen by a doctor and (5) medical staffing
      levels. Outcomes of interest for this study were shift perception scores (1=very
      poor to 5=very good) and daily ED performance measures. Performance measures were
      the proportion of patients admitted or discharged from ED within 4 h (National
      Emergency Access Target, NEAT) and the percentage of inpatient admissions leaving
      ED within 8 h of ED arrival time. RESULTS: The number of patients in ED with LOS
      >4 h (OR 0.83, 95% CI 0.79 to 0.87, p value <0.001) and number of patients
      waiting to be seen (OR 0.92, 95% CI 0.88 to 0.95, p value <0.001) were the
      factors most strongly associated with shift perception score. After adjustment,
      the mean NEAT performance improved 6% for each incremental increase in average
      shift perception score (beta=0.06 95% CI 0.04 to 0.07, p<0.001). CONCLUSIONS:
      Shift reports and shift perceptions by emergency physicians may be used to
      predict overall ED performance.

PMID- 24022114
TI  - Coexistence and expression profiles of two alternative splice variants of the
      pheromone receptor gene pre-1 in Neurospora crassa.
AB  - In this study, we show that two splice variants of the pheromone receptor gene
      (pre-1) transcript coexist in vegetative and reproductive tissues of the
      filamentous ascomycete fungus Neurospora crassa. The two splice variants differ
      by intron retention of the last intron, which is predicted to result in a
      premature stop codon and loss of 322 amino acids in the C-terminal cytosolic
      region of PRE-1. Using quantitative PCR, we show that expression of the variants
      is influenced by mating type (mat), with a higher proportion of intron-spliced
      transcripts in a mat A strain and a higher proportion of the intron-retained
      variant in a mat a strain. The intron-retained PRE-1 variant is predicted to lack
      6 ubiquitination sites that may influence receptor function. In conclusion, N.
      crassa produce two pre-1 splice variants that display different transcription
      profiles.

PMID- 24022116
TI  - Swallow your pride.

PMID- 24022115
TI  - Cross-cultural studies of menopause: the challenge continues.

PMID- 24022117
TI  - Detection of phenazepam in impaired driving.
AB  - Phenazepam is a potent 1,4-benzodiazepine that has gained notoriety among
      recreational drug users. First synthesized in Ukraine in the 1970s, it is one of
      the most commonly prescribed benzodiazepines in Russia and other commonwealth of
      independent state nations, where it is used therapeutically as a prescription
      drug. Reports of abuse are widespread and several European countries have taken
      steps to control its use. However, in the USA, phenazepam is not approved for use
      by the Food and Drug Administration, nor scheduled under the Federal Controlled
      Substances Act. Phenazepam is widely available on the Internet, and recreational
      drug users report a potency 10-fold greater than that of nordiazepam. We report a
      case of a 24-year-old male driver who was apprehended for impaired driving
      following a two-vehicle crash. The subject exhibited slurred speech and profound
      psychomotor impairment. Toxicology testing revealed phenazepam at a concentration
      of 76 ng/mL in blood, with no other drugs detected. This case report not only
      demonstrates the potential for adverse traffic safety consequences following the
      misuse of phenazepam, but also highlights the importance of analytical factors
      such as immunoassay cutoff concentration, cross-reactivity and comprehensive
      screening using chromatographic-based techniques for impaired driving
      investigations. 

PMID- 24022119
TI  - An asymmetric tubular ceramic-carbonate dual phase membrane for high temperature
      CO2 separation.
AB  - For the first time, a tubular asymmetric ceramic-carbonate dual phase membrane
      was prepared by a centrifugal casting technique and used for high temperature CO2
      separation. This membrane shows high CO2 permeation flux and permeance. 

PMID- 24022118
TI  - Annexin A6 interacts with p65 and stimulates NF-kappaB activity and catabolic
      events in articular chondrocytes.
AB  - OBJECTIVE: ANXA6, the gene for annexin A6, is highly expressed in osteoarthritic
      (OA) articular chondrocytes but not in healthy articular chondrocytes. This study
      was undertaken to determine whether annexin A6 affects catabolic events in these
      cells. METHODS: Articular chondrocytes were isolated from Anxa6-knockout mice,
      wild-type (WT) mice, and human articular cartilage in which ANXA6 was
      overexpressed. Cells were treated with interleukin-1beta (IL-1beta) or tumor
      necrosis factor alpha (TNFalpha), and expression of catabolic genes and
      activation of NF-kappaB were determined by real-time polymerase chain reaction
      and luciferase reporter assay. Anxa6(-/-) and WT mouse knee joints were injected
      with IL-1beta or the medial collateral ligament was transected and partial
      resection of the medial meniscus was performed to determine the role of Anxa6 in
      IL-1beta-mediated cartilage destruction and OA progression. The mechanism by
      which Anxa6 stimulates NF-kappaB activity was determined by coimmunoprecipitation
      and immunoblot analysis of nuclear and cytoplasmic fractions of IL-1beta-treated
      Anxa6(-/-) and WT mouse chondrocytes for p65 and Anxa6. RESULTS: Loss of Anxa6
      resulted in decreased NF-kappaB activation and catabolic marker messenger RNA
      (mRNA) levels in IL-1beta- or TNFalpha-treated articular chondrocytes, whereas
      overexpression of ANXA6 resulted in increased NF-kappaB activity and catabolic
      marker mRNA levels. Annexin A6 interacted with p65, and loss of Anxa6 caused
      decreased nuclear translocation and retention of the active p50/p65 NF-kappaB
      complex. Cartilage destruction in Anxa6(-/-) mouse knee joints after IL-1beta
      injection or partial medial meniscectomy was reduced as compared to that in WT
      mouse joints. CONCLUSION: Our data define a role of annexin A6 in the modulation
      of NF-kappaB activity and in the stimulation of catabolic events in articular
      chondrocytes.

PMID- 24022120
TI  - Abrupt rise of new machine ecology beyond human response time.
AB  - Society's techno-social systems are becoming ever faster and more computer
      orientated. However, far from simply generating faster versions of existing
      behaviour, we show that this speed-up can generate a new behavioural regime as
      humans lose the ability to intervene in real time. Analyzing millisecond-scale
      data for the world's largest and most powerful techno-social system, the global
      financial market, we uncover an abrupt transition to a new all-machine phase
      characterized by large numbers of subsecond extreme events. The proliferation of
      these subsecond events shows an intriguing correlation with the onset of the
      system-wide financial collapse in 2008. Our findings are consistent with an
      emerging ecology of competitive machines featuring 'crowds' of predatory
      algorithms, and highlight the need for a new scientific theory of subsecond
      financial phenomena. 

PMID- 24022121
TI  - The azaphosphiridine to terminal phosphinidene complex rearrangement--looking for
      non-covalent interactions of a highly reactive species.
AB  - Azaphosphiridine complexes 4a,a', intermediates in the reaction of P-C5Me5
      substituted Li-Cl phosphinidenoid complex 2 and C-furyl carbaldimine 3,
      rearranged selectively to give the novel N,P,C-cage complex 5a. Transient
      terminal phosphinidene complex 7a was trapped with phenyl acetylene (8) forming
      the new N,P,C-cage complex 9. DFT calculations provide evidence for a thermally
      allowed aza-phospha-Cope rearrangement that led to the P-amino substituted
      phosphinidene complex 7a, which is stabilized by non-covalent interactions in
      addition to typical through-bond electronic effects.

PMID- 24022122
TI  - Proteomic sample preparation from formalin fixed and paraffin embedded tissue.
AB  - Preserved clinical material is a unique source for proteomic investigation of
      human disorders. Here we describe an optimized protocol allowing large scale
      quantitative analysis of formalin fixed and paraffin embedded (FFPE) tissue. The
      procedure comprises four distinct steps. The first one is the preparation of
      sections from the FFPE material and microdissection of cells of interest. In the
      second step the isolated cells are lysed and processed using 'filter aided sample
      preparation' (FASP) technique. In this step, proteins are depleted from reagents
      used for the sample lysis and are digested in two-steps using endoproteinase LysC
      and trypsin. After each digestion, the peptides are collected in separate
      fractions and their content is determined using a highly sensitive fluorescence
      measurement. Finally, the peptides are fractionated on 'pipette-tip'
      microcolumns. The LysC-peptides are separated into 4 fractions whereas the
      tryptic peptides are separated into 2 fractions. In this way prepared samples
      allow analysis of proteomes from minute amounts of material to a depth of 10,000
      proteins. Thus, the described workflow is a powerful technique for studying
      diseases in a system-wide-fashion as well as for identification of potential
      biomarkers and drug targets. 

PMID- 24022123
TI  - Inactivated quadrivalent split-virus seasonal influenza vaccine (Fluarix(r)
      quadrivalent): a review of its use in the prevention of disease caused by
      influenza A and B.
AB  - The inactivated quadrivalent split-virus seasonal influenza vaccine [Fluarix(r)
      quadrivalent, manufactured in Dresden (D-QIV)] contains 15 MUg haemagglutinin
      from each of the four influenza virus strains expected to circulate in the
      upcoming influenza season. Unlike seasonal trivalent influenza vaccines (TIVs),
      which have been used previously, quadrivalent influenza vaccines (QIVs) contain
      two influenza A subtype viruses and two B type viruses. As two different B
      viruses have co-circulated in recent years, incorporating both B lineages reduces
      the risk of the dominant B strain not being included in the vaccine. D-QIV is
      approved for active immunization of individuals aged >=3 years to prevent disease
      caused by the influenza A subtype viruses and B type viruses contained in the
      vaccine. In large randomized, controlled trials, D-QIV was highly immunogenic in
      healthy adults (including individuals aged >=65 years) and children, and exceeded
      the criteria for vaccine licensure. Immune responses for D-QIV, compared with
      those for TIVs, were non-inferior against influenza A strains and common B
      strains and superior against the additional B strain. D-QIV was generally well
      tolerated in all age groups studied and, overall, reactogenicity and tolerability
      were generally similar to observations with TIVs. Quadrivalent influenza vaccines
      are expected to offer substantial cost-effectiveness benefits in seasons where
      the B lineage selected for inclusion in TIVs does not match the dominant
      circulating strain. Thus, by incorporating both circulating influenza B lineages,
      vaccination with D-QIV is likely to reduce the risk of the dominant circulating B
      type virus not matching the strain selected for the vaccine and, therefore, more
      effectively protect target populations from influenza than TIVs.

PMID- 24022124
TI  - Modelling electric field control of the spin state in the mixed-valence
      polyoxometalate [GeV14O40]8-.
AB  - The two-electron reduced mixed-valence polyoxometalate [GeV14O40](8-) presents an
      unusual paramagnetic behaviour as a consequence of the partial trapping of these
      electrons. The effect of applying an electric field is that of inducing
      antiferromagnetic coupling between the two delocalized electronic spins. 

PMID- 24022125
TI  - Interleukin-17 signalling in a murine model of mild chronic asthma.
AB  - BACKGROUND: The role of Th17 cell-derived cytokines in the pathogenesis of airway
      inflammation and remodelling in mild asthma remains unclear. We investigated this
      in a mouse model which reproduces most of the features of the human disease.
      METHODS: Systemically sensitised BALB/c mice were challenged via the airways with
      a low mass concentration of ovalbumin aerosol for 8 weeks to induce lesions of
      mild chronic asthma. Changes were compared with those in animals deficient in
      signalling via the interleukin (IL)-17 receptor A (IL-17R). Low-passage airway
      epithelial cells (AEC) and fibroblasts were cultured with IL-17A, or with media
      from Th17-polarised cells, to assess activation. RESULTS: In CD4+ T cells from
      chronically challenged mice, expression of mRNA for Th17 cytokines IL-17A, IL
      17F, IL-21 and IL-22 was significantly increased. Both recombinant IL-17A and
      media from Th17 cells significantly stimulated the production of various pro
      inflammatory and pro-remodelling cytokines by AEC and fibroblasts. In the mouse
      model, abrogation of IL-17R signalling had no effect on the development of airway
      inflammation or on most changes of remodelling. However, numbers of mucus
      producing cells and expression of mRNA for Gob-5 were attenuated in the absence
      of IL-17R signalling. CONCLUSIONS: Although IL-17A and Th17 cells stimulate
      cytokine production by structural cells of the airways, and Th17 cells are
      induced in our model of mild chronic asthma, signalling via IL-17R did not
      contribute significantly to the development of airway inflammation and most
      changes of remodelling in this model. However, in mild asthma, IL-17A appears to
      have a role in the goblet cell response in the airways.

PMID- 24022126
TI  - Systematic analysis of intron size and abundance parameters in diverse lineages.
AB  - All eukaryotic genomes have genes with introns in variable sizes. As far as
      spliceosomal introns are concerned, there are at least three basic parameters to
      stratify introns across diverse eukaryotic taxa: size, number, and sequence
      context. The number parameter is highly variable in lower eukaryotes, especially
      among protozoan and fungal species, which ranges from less than 4% to 78% of the
      genes. Over greater evolutionary time scales, the number parameter undoubtedly
      increases as observed in higher plants and higher vertebrates, reaching greater
      than 12.5 exons per gene in average among mammalian genomes. The size parameter
      is more complex, where multiple modes appear at work. Aside from intronless
      genes, there are three other types of intron-containing genes: half-sized,
      minimal, and size-expandable introns. The half-sized introns have only been found
      in a limited number of genomes among protozoan and fungal lineages and the other
      two types are prevalent in all animal and plant genomes. Among the size
      expandable introns, the sizes of plant introns are expansion-limited in that the
      large introns exceeding 1000 bp are fewer in numbers and transposon-free as
      compared to the large introns among animals, where the larger introns are filled
      with transposable elements and appear expansion-flexible, reaching several
      kilobasepairs (kbp) and even thousands of kbp in size. Most of the intron
      parameters can be studied as signatures of the specific splicing machineries of
      different eukaryotic lineages and are highly relevant to the regulation of gene
      expression and functionality. In particular, the transcription-splicing-export
      coupling of eukaryotic intron dispensing leads to a working hypothesis that all
      intron parameters are evolved to be efficient and function-related in processing
      and routing the spliced transcripts.

PMID- 24022127
TI  - Diagnostic challenges in Balamuthia mandrillaris infections.
AB  - Balamuthia mandrillaris is an emerging cause of subacute granulomatous amebic
      encephalitis (GAE). The diagnosis of this infection has proven to be difficult
      and is usually made postmortem. Early recognition and treatment may offer some
      benefit. This report describes a previously healthy woman who died from GAE due
      to B. mandrillaris.

PMID- 24022128
TI  - Ligophorus spp. (Monogenoidea: Dactylogyridae) parasitizing mullets (Teleostei:
      Mugiliformes: Mugilidae) occurring in the fresh and brackish waters of the Shatt
      Al-Arab River and Estuary in southern Iraq, with the description of Ligophorus
      sagmarius sp. n. from the greenback mullet Chelon subviridis (Valenciennes).
AB  - The gills of three of five species of mullets (Teleostei: Mugiliformes:
      Mugilidae) collected from the brackish and fresh waters of southern Iraq were
      infected with species of Ligophorus (Monogenoidea: Dactylogyridae) as follows:
      greenback mullet Chelon subviridis (Valenciennes) infected with Ligophorus
      lebedevi Dmitrieva, Gerasev, Gibson, Pronkina and Galli, 2012, Ligophorus
      bantingensis Soo and Lim, 2012, Ligophorus sagmarius n. sp., and Ligophorus
      fluviatilis (Bychowsky, 1949) Dmitrieva, Gerasev, Gibson, Pronkina, and Galli,
      2012; Klunzinger's mullet Liza klunzingeri (Day) with L. bantingensis, L.
      fluviatilis, and an apparently undescribed species of Ligophorus; and abu mullet
      Liza abu (Heckel) with L. bantingensis and L. fluviatilis. The keeled mullet Liza
      carinata (Valenciennes) and Speigler's mullet Valamugil speigleri (Bleeker) were
      uninfected. L. sagmarius n. sp. is described, and L. lebedevi and L. bantingensis
      are redescribed. Available specimens of L. fluviatilis and the undescribed
      species of Ligophorus from Klunzinger's mullet were insufficient for description.

PMID- 24022129
TI  - Integrative taxonomy identifies a new species of Phyllodistomum (Digenea:
      Gorgoderidae) from the twospot livebearer, Heterandria bimaculata (Teleostei:
      Poeciliidae), in Central Veracruz, Mexico.
AB  - Phyllodistomum inecoli n. sp. is described from the twospot livebearer,
      Heterandria bimaculata (Teleostei: Poeciliidae), collected in the Rio La Antigua
      basin, Veracruz, Mexico. The new species is described and characterised by using
      a combination of morphology, scanning electron microscopy, and sequences of
      nuclear and mitochondrial genes. Diagnostic characters of the new species of
      Phyllodistomum include a genital pore opening at the level of the caecal
      bifurcation; oval vitellarium, situated just posterior to the ventral sucker and
      not extended laterally and anterior extracaecal uterine loops variable in
      extension (reaching the anterior, median or posterior margin of the ventral
      sucker). P. inecoli n. sp. most closely resembles P. brevicecum, a species
      described as a parasite of the central mudminnow, Umbra limi, in other parts of
      North America; however, the genital pore in P. brevicecum is situated between the
      caecal bifurcation and the ventral sucker, the ovary is larger, the vitellarium
      is lobed and extended laterally and the anterior portion of the uterus extends to
      the posterior margin of the ventral sucker. Comparison of about 1,500-2,200
      nucleotides of cox1 and 28S rDNA and ITS1 strongly supports the status of P.
      inecoli as a new species. Bayesian inference analysis of combined datasets of 28S
      rDNA and cox1 sequences showed that P. inecoli n. sp. and the other species found
      in freshwater fishes of Mexico, including the species complex of P. lacustri, are
      not sister species. Phylogenetic analysis based on 28S rDNA sequences of several
      gorgoderid taxa revealed the close relationship of P. inecoli n. sp. with several
      species of Phyllodistomum, Gorgodera and Gorgoderina with cystocercous cercariae
      developing in sphaeriid bivalves. Dot-plot analysis of ITS1 sequences of P.
      inecoli n. sp. revealed the presence of eight repetitive elements with different
      length, which together represent almost half the length of ITS1.

PMID- 24022130
TI  - Surgical resection of hepatic metastasis from gastric cancer:  a review and new
      recommendation in the Japanese gastric cancer  treatment guidelines.
AB  - Liver metastases from gastric cancer are rarely indicated for surgery because
      they are often diagnosed as multiple nodules occupying both lobes and coexist
      with extra hepatic disease. A literature search identified no clinical trials on
      hepatectomy for this disease; only retrospective studies of a relatively small
      number of cases collected over more than a decade, mostly from a single
      institution, were found. Five-year survival rates from these reports ranged from
      0 % to 37 %, and long-term survivors were observed among carefully selected case
      series. The most commonly reported prognostic factor was the number of metastatic
      nodules, and patients with a solitary metastasis tended to have superior outcome.
      Patients diagnosed to have a small number of metastatic nodules by modern imaging
      tools could be indicated for surgery. Because both intrahepatic and extrahepatic
      recurrences are common,patients are likely to benefit from perioperative adjuvant
      chemotherapy, although it is not possible at this time to specify which regimen
      is the most appropriate

PMID- 24022131
TI  - Contrary to popular belief.

PMID- 24022132
TI  - J&J courts biotech in clusters.

PMID- 24022133
TI  - Doubts raised over 'read-through' Duchenne drug mechanism.

PMID- 24022137
TI  - Amgen best-seller challenged by generics.

PMID- 24022140
TI  - First Axl inhibitor enters clinical trials.

PMID- 24022142
TI  - Greenpeace campaign prompts Philippine ban on Bt eggplant trials.

PMID- 24022145
TI  - Biotechs to tap into Horizon 2020's $93 billion.

PMID- 24022147
TI  - At the frontiers of lung fibrosis therapy.

PMID- 24022149
TI  - Falling prices and unfair competition in consumer genomics.

PMID- 24022150
TI  - The ethics of participant-led biomedical research.

PMID- 24022151
TI  - Systematic investigation of cancer-associated somatic point mutations in SNP
      databases.

PMID- 24022152
TI  - Economic and environmental impacts of microbial biodiesel.

PMID- 24022153
TI  - How safe does transgenic food need to be?

PMID- 24022154
TI  - Maximizing the commercial value of personalized therapeutics and companion
      diagnostics.

PMID- 24022157
TI  - Cages from coils.

PMID- 24022156
TI  - Staying on target with CRISPR-Cas.

PMID- 24022159
TI  - Programming CMV for vaccine vector design.

PMID- 24022160
TI  - Commensal cocktail suppresses gut inflammation.

PMID- 24022161
TI  - An interdisciplinary shift in demand for talent within the biotech industry.

PMID- 24022164
TI  - Granulocyte macrophage colony-stimulating factor shows anti-apoptotic activity
      via the PI3K-NF-kappaB-HIF-1alpha-survivin pathway in mouse neural progenitor
      cells.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic
      cytokine that plays a crucial role in regulating the proliferation,
      differentiation, and survival of hematopoietic cells. Recent studies have shown
      that GM-CSF also has anti-apoptotic effects and regulates the expression of anti
      apoptotic genes including Bcl-2 family proteins in neuronal cells in vitro and in
      vivo. However, the mechanism underlying the anti-apoptotic function of GM-CSF is
      not well understood. In the present work, we examined the role of
      phosphoinositide 3-kinase (PI3K)-AKT signal pathway in the anti-apoptotic
      activity of GM-CSF in mouse neural progenitor cells (NPCs). In terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, the anti
      apoptotic effect of GM-CSF (apoptotic population of approximately 8.17 %) on
      staurosporine-induced apoptosis of NPCs (31.09 %) was significantly blocked by
      LY294002, an inhibitor of PI3K signal (24.04 %). We found that the PI3K-AKT
      signal pathway induced by GM-CSF treatment activated nuclear factor kappaB (NF
      kappaB) and increased the expression of hypoxia-inducible factor 1alpha (HIF
      1alpha) in normoxic conditions. Analyses using specific small interfering RNAs
      (siRNAs) showed that NF-kappaB was an upstream molecule of HIF-1alpha and
      activated its expression at the mRNA level. Further analyses using the siRNAs and
      chromatin immunoprecipitation (ChIP) showed that HIF-1alpha was responsible for
      the induced expression of survivin, a member of the inhibitor of apoptosis
      proteins (IAPs). Each of the specific siRNAs for NF-kappaB, HIF-1alpha, and
      survivin inhibited significantly the anti-apoptotic activity of GM-CSF on the
      staurosporine-induced apoptosis in NPCs in TUNEL assays. The results of this
      study showed the downstream signals and mechanism of PI3K/AKT-mediated anti
      apoptotic activity of GM-CSF in NPCs, particularly revealing the role of the NF
      kappaB-HIF-1alpha-survivin cascade.

PMID- 24022166
TI  - The cardiorenal syndrome: what the cardiologist needs to know.
AB  - Interactions between the heart and the kidneys are increasingly acknowledged
      among both cardiologists and nephrologists. The term cardiorenal syndrome now
      applies to the bidirectional nature of how disease in one organ system affects
      the function of the other organ system. Cardiovascular disease is a major threat
      to patients with chronic kidney disease, while renal dysfunction is prevalent in
      patients with cardiac disease and is a significant predictor of prognosis in
      cardiac patients. Still, renal patients with cardiac disease have largely been
      excluded from the clinical trials that have been the basis of modern cardiologic
      treatment. In this review, the current understanding of the pathophysiological
      mechanisms involved in the cardiorenal syndrome and potential therapeutic
      implications will be summarized from a nephrologist's point of view. Probably,
      fragile cardiorenal patients will benefit from an enhanced collaboration between
      cardiologists and nephrologists to secure the best treatment given under safe
      conditions. 

PMID- 24022167
TI  - Repository needed to improve access to drug company documents, conference hears.

PMID- 24022168
TI  - Journals are not biased towards positive trial results, conference hears.

PMID- 24022163
TI  - GABAA receptor-mediated tonic depolarization in developing neural circuits.
AB  - The activation of GABAA receptors (the type A receptors for gamma-aminobutyric
      acid) produces two distinct forms of responses, phasic (i.e., transient) and
      tonic (i.e., persistent), that are mediated by synaptic and extrasynaptic GABAA
      receptors, respectively. During development, the intracellular chloride levels
      are high so activation of these receptors causes a net outward flow of anions
      that leads to neuronal depolarization rather than hyperpolarization. Therefore,
      in developing neural circuits, tonic activation of GABAA receptors may provide
      persistent depolarization. Recently, it became evident that GABAA receptor
      mediated tonic depolarization alters the structure of patterned spontaneous
      activity, a feature that is common in developing neural circuits and is important
      for neural circuit refinement. Thus, this persistent depolarization may lead to a
      long-lasting increase in intracellular calcium level that modulates network
      properties via calcium-dependent signaling cascades. This article highlights the
      features of GABAA receptor-mediated tonic depolarization, summarizes the
      principles for discovery, reviews the current findings in diverse developing
      circuits, examines the underlying molecular mechanisms and modulation systems,
      and discusses their functional specializations for each developing neural
      circuit. 

PMID- 24022169
TI  - Illicit drug use in the US holds steady, but heroin use is on rise.

PMID- 24022170
TI  - Health secretary's remarks about GPs are "morale sapping," says royal college.

PMID- 24022171
TI  - Hospital merger is jeopardised by private provider's objections.

PMID- 24022172
TI  - Practice guidelines for the supervising professional: intraoperative
      neurophysiological monitoring.
AB  - The American Society of Neurophysiological Monitoring (ASNM) was founded in 1988
      as the American Society of Evoked Potential Monitoring. From the beginning, the
      Society has been made up of physicians, doctoral degree holders, technologists,
      and all those interested in furthering the profession. The Society changed its
      name to the ASNM and held its first Annual Meeting in 1990. It remains the
      largest worldwide organization dedicated solely to the scientifically based
      advancement of intraoperative neurophysiology. The primary goal of the ASNM is to
      assure the quality of patient care during monitored procedures along the
      neuraxis. This goal is accomplished through programs in education, advocacy of
      basic and clinical research, and publication of guidelines. The ASNM is committed
      to the development of medically sound and clinically relevant guidelines for
      intraoperative neurophysiology. Guidelines are formulated based on exhaustive
      literature review, recruitment of expert opinion, and broad consensus among ASNM
      membership. Input is likewise sought from sister societies and related
      constituencies. Adherence to a literature-based, formalized process characterizes
      the construction of all ASNM guidelines. The guidelines covering the Professional
      Practice of intraoperative monitoring were established by a committee of nearly
      30 total participants and ultimately endorsed by the Board of Directors of ASNM
      on January 24th 2013. That document follows.

PMID- 24022173
TI  - Hybrid microfabrication of nanofiber-based sheets and rods for tissue engineering
      applications.
AB  - Electrospun nanofibers have been developed into a variety of forms for tissue
      engineering scaffolds to regulate the cellular functions guided by
      nanotopographical cues. Here, we have successfully fabricated nanofiber-based
      scaffold complexes of rod and sheet type by combining the three microfabrication
      techniques of electrospinning, spin coating, and polymer melt deposition. It was
      demonstrated that this hybrid fabrication could produce uniaxially aligned
      nanofiber scaffolds supported by a thin film, allowing for a mechanically
      enforced substrate for cell culture as well as facile scaffold manipulation. The
      results of cell analysis indicated that nanofibers on spin-coated films could
      provide contact guidance effects on cells and retain them even after
      manipulation. As an application of the cell-laden nanofiber film, we built a rod
      type structure by rolling up the film around a mechanically supporting core
      microfiber, which was incorporated by polymer melt deposition. A biocompatible
      and biodegradable polymer, polycaprolactone, was used throughout the processes
      and thus could be used as a directly implantable substitute in tissue
      regeneration. 

PMID- 24022174
TI  - Screening for left ventricular dysfunction in the community: ready for prime
      time?

PMID- 24022175
TI  - Preattentive processing of horizontal motion, radial motion, and intensity
      changes of sounds.
AB  - Localization of sound sources is critical for an appropriate behavioral response.
      This is not only true for localization in the horizontal plane but also for
      localization in depth. Depth ranging of sound sources implicates various distance
      cues, among others sound intensity. In this study, we measured human
      electroencephalography and compared mismatch negativity (MMN) amplitudes and
      latencies for horizontal motion, radial motion, and pure intensity changes in the
      free field. We observed similar MMN latencies for horizontal and radial motion,
      whereas MMN responses to pure intensity changes were comparably delayed. MMN
      amplitudes and latencies were not different for approaching and receding sounds.
      Our data suggest similar fast processing for horizontal and radial motion,
      whereas pure intensity changes are possibly processed with less priority. 

PMID- 24022177
TI  - Aberrant increase in cytochrome c oxidase subunit I precedes neuronal death after
      cerebral ischemia.
AB  - Cerebral ischemia is known to produce excessive reactive oxygen species in
      mitochondria, and these radicals initiate radical chain reactions, causing
      cellular macromolecule damage, and also promote the mitochondrial apoptosis
      pathway, ultimately leading to cell death. However, little is known about the
      mitochondrial functional alterations after ischemia. The authors examined the
      expression of cytochrome c oxidase (COX), a terminal, rate-limiting enzyme of the
      electron transport chain to generate ATP, after global cerebral ischemia in rats.
      Immunofluorescent staining and western blot were performed to investigate the
      spatial and temporal changes in two important COX subunits: mitochondrion-encoded
      COX subunit I (COX I) and nucleus-encoded COX subunit IV (COX IV). Under the
      normal condition, these subunits have to be regulated precisely in a 1 : 1
      stoichiometry to assemble the functional COX holoenzyme. In this study, a huge
      increase in COX I, which is disproportionate to COX IV, was observed in the early
      stage after lethal ischemia, preceding delayed neuronal death. In contrast, mild
      sublethal ischemia did not induce obvious changes in COX I and IV. This aberrant
      increase in COX I may be an early sign of delayed neuronal death or may predict
      later electron transport chain dysfunction to generate ATP. 

PMID- 24022176
TI  - Effects of exercise on resting-state default mode and salience network activity
      in overweight/obese adults.
AB  - Despite the common use of exercise as a weight-loss strategy, little is known
      about its neuronal effects, and how these may be related to cognitive changes
      that impact food intake. The current study assessed the effects of a 6-month
      exercise intervention on intrinsic activity in the default mode network (DMN), a
      functionally connected network of brain regions including posterior cingulate
      cortex, cuneus/precuneus, medial prefrontal cortex, medial temporal lobe, and
      inferior parietal cortices, and salience network, which includes the anterior
      cingulate cortex and insula. Resting-state functional MRI data were acquired in
      12 overweight/obese individuals. The intervention was associated with a reduction
      in DMN activity in the precuneus (P=0.003, family-wise error-corrected), which
      was associated with greater fat mass loss (P=0.013) as well as reduced perceived
      hunger (Three Factor Eating Questionnaire, P=0.024) and hunger ratings in
      response to a meal (P=0.013). No changes were observed in the salience network in
      response to the exercise intervention. The association between DMN change and
      both fat mass loss and reduction of hunger ratings suggests that DMN function may
      be involved in the regulation of food intake behaviors. Given previous reports of
      DMN overactivity in overweight/obese individuals, the present findings may
      indicate an exercise-related 'normalization' of network function. 

PMID- 24022178
TI  - Investigation of the direct hepatic effects of intramuscular interleukin-8
      injection in an experimental rabbit model.
AB  - BACKGROUND: The aim of this study was to investigate the effects of intramuscular
      IL-8 injection on hepatic tissues using an in vivo histopathological animal
      model. MATERIAL AND METHODS: Twelve New Zealand white rabbits were used for this
      randomized, controlled, single-blinded interventional study. For 6 days, 1
      gluteus maximus muscle was injected daily with 1 mcg/kg of IL-8 in 6 rabbits
      (Group A). The remaining 6 rabbits (to determine to normal porto-hepatic
      morphology of the rabbit genus) were in the sham group (Group B). At the end of
      the 7th day, all rabbits were killed and livers were meticulously harvested.
      Microscopically, regional tissues were scored according to portal inflammation,
      focal necrosis, piecemeal necrosis, and total impact. RESULTS: Total impact
      score, portal inflammation, focal necrosis, and piecemeal necrosis were the
      histopathologic changes present in a higher incidence in the IL-8 group compared
      with the control group. The differences were significant when the groups were
      compared according to total impact score, portal inflammation, focal necrosis,
      and piecemeal necrosis according to Pearson's correlation (p<0.05). The most
      significant differences were detected at the total impact scores (p=0.002) and
      the portal inflammation scores (p=0.008). CONCLUSIONS: Our results showed that IL
      8 may damage hepatocytes. This can be the determined target for new therapeutic
      strategies. Further trials should be designed to obtain definitive results.

PMID- 24022179
TI  - Patterns of sensitization to inhalant and food allergens - findings from the
      German Health Interview and Examination Survey for Children and Adolescents.
AB  - BACKGROUND: To assess the prevalence of allergic sensitization and to analyze
      patterns of sensitization to common inhalant and food allergens in a nationwide
      representative sample of children and adolescents in Germany. METHODS: Data were
      collected from 2003 to 2006 within the KiGGS, the national Health Interview and
      Examination Survey covering a representative sample of 17,641 children and
      adolescents in Germany. Immunoglobulin E (IgE) antibodies to 20 specific
      allergens (11 inhalant and 9 food allergens) were quantitatively measured in a
      subsample of 12,988 KiGGS participants aged 3-17 years using the ImmunoCAP
      system. Serum concentrations >=0.35 kU/l indicate sensitized participants. An
      exploratory factor analysis was performed in order to identify sensitization
      patterns. RESULTS: Sensitization to at least 1 of the 20 tested allergens was
      detected in 40.2% [95% confidence interval (CI) 39.0-41.4] of the participants.
      The highest sensitization prevalences were found for pollen from Timothy grass
      (22.7%; 21.5-23.9) and rye (21.2%; 20.0-22.4). Sensitization was more prevalent
      in boys than in girls and prevalence increased generally with increasing age. We
      identified seven sensitization groups, namely (in descending order of magnitude)
      'Timothy grass/rye', 'house-dust mites', 'food/mugwort', 'birch/apple',
      'animals', 'cow's milk/egg white' and 'moulds'. CONCLUSIONS: Allergic
      sensitization is common in German children and adolescents. The fact that
      sensitization potentially leads to clinically relevant allergic diseases stresses
      the public health relevance of this topic. Whether the grouping reflects the
      propensity for persons to be sensitized to multiple allergens within a group, or
      whether it is due to IgE cross-reactivity between different allergens of similar
      structure is still being discussed.

PMID- 24022180
TI  - At home among strangers: Alfred Russel Wallace in Russia.
AB  - Alfred Russel Wallace (1823-1913) was an influential figure within Russian pre
      Synthetic evolutionary biology, i.e. the time period before the Synthetic Theory
      of Evolution was established (ca. 1880-1930s). His major works were translated
      into Russian and his general ideas were read and discussed by both insiders and
      outsiders of scientific evolutionism. At the same time, Wallace played a
      controversial role in the growth of Darwinism in Russia, and Charles Robert
      Darwin (1809-1882) has eclipsed Wallace in his influence on Russian evolutionary
      thinking. In this paper we briefly outline Wallace's impact on Russian pre
      Synthetic scientific evolutionism and its general intellectual climate. We
      demonstrate that both Russian pro-Darwinian evolutionists and anti-Darwinians
      (scientific anti-Darwinians as well as creationists) were fully aware of
      Wallace's contributions to the development of evolutionary theory. Yet, Wallace's
      radical selectionism, as well as his controversial arguments for "design in
      nature", predetermined his special place within the Russian intellectual
      landscape.

PMID- 24022181
TI  - Gentrification and preterm birth in New York City, 2008-2010.
AB  - Adverse birth outcomes have been linked to neighborhood level socioeconomic
      status. However, little work has examined the influence of social and economic
      change over time (i.e., gentrification) on health. This study aims to assess the
      association between gentrification and preterm birth (PTB) while examining the
      modifying effect of maternal race/ethnicity and educational attainment. New York
      City births, 2008-2010, (n=126,165) were linked to a measure of gentrification at
      the community district level (n=59). The gentrification measure was calculated
      using percent change in education level, poverty level, and median household
      income (MHI) between the 2005-2009 American Community Survey and the 1990 Census.
      PTB was defined as clinical gestational age less than 37 weeks. Generalized
      estimating equations were utilized to examine the association. Gentrification
      (i.e., increase in residents with a college education, increase in MHI, and
      decrease in residents living below the poverty line) was not associated with PTB.
      However, among Non-Hispanic Blacks, very high gentrification was adversely
      associated with PTB (AOR, 1.16; 95 % CI, 1.01-1.33) as compared to those who
      lived in a very low gentrified neighborhood. Among non- Hispanic Whites, living
      in a very high gentrified neighborhood was protective as compared to living in a
      very low gentrified neighborhood (AOR, 0.78; 95 % CI, 0.64- 0.94). Although there
      is a need to develop a more nuanced measure of gentrification, these results
      indicate that changes in the economic character of a neighborhood may have a
      significant influence on birth outcomes.

PMID- 24022182
TI  - Lessons from Hurricane Sandy: a community response in Brooklyn, New York.
AB  - The frequency and intensity of extreme weather events have increased in recent
      decades; one example is Hurricane Sandy. If the frequency and severity continue
      or increase, adaptation and mitigation efforts are needed to protect vulnerable
      populations and improve daily life under changed weather conditions. This field
      report examines the devastation due to Hurricane Sandy experienced in Red Hook,
      Brooklyn, New York, a neighborhood consisting of geographically isolated low
      lying commercial and residential units, with a concentration of low-income
      housing, and disproportionate rates of poverty and poor health outcomes largely
      experienced by Black and Latino residents. Multiple sources of data were
      reviewed, including street canvasses, governmental reports, community flyers, and
      meeting transcripts, as well as firsthand observations by a local nonprofit Red
      Hook Initiative (RHI) and community members, and social media accounts of the
      effects of Sandy and the response to daily needs. These data are considered
      within existing theory, evidence, and practice on protecting public health during
      extreme weather events. Firsthand observations show that a community-based
      organization in Red Hook, RHI, was at the center of the response to disaster
      relief, despite the lack of staff training in response to events such as
      Hurricane Sandy. Review of these data underscores that adaptation and response to
      climate change and likely resultant extreme weather is a dynamic process
      requiring an official coordinated governmental response along with on-the-ground
      volunteer community responders.

PMID- 24022183
TI  - Intramolecular arylation of amino acid enolates.
AB  - Dianionic enolates formed from N'-aryl urea derivatives of amino acids undergo
      intramolecular C-arylation by attack of the enolate anion on the N'-aryl ring,
      leading to a hydantoin derivative of a quaternary amino acid. In situ IR studies
      allow identification of four intermediates on the reaction pathway. 

PMID- 24022184
TI  - Intake of coffee, caffeine and other methylxanthines and risk of Type I vs Type
      II endometrial cancer.
AB  - BACKGROUND: Coffee and other sources of methylxanthines and risk of Type I vs
      Type II endometrial cancer (EC) have not been evaluated previously. METHODS:
      Prospective cohort of 23,356 postmenopausal women with 471 Type I and 71 Type II
      EC cases. RESULTS: Type I EC was statistically significantly associated with
      caffeinated (relative risk (RR)=0.65 for 4+ cups per day vs <=1 cup per month:
      95% confidence interval (CI): 0.47-0.89) but not decaffeinated (RR=0.76; 95% CI:
      0.50-1.15) coffee intake; there were no associations with tea, cola or chocolate,
      or for Type II EC. The inverse association with caffeinated coffee intake was
      specific to women with a body mass index 30+ kg m(-2) (RR=0.56; 95% CI: 0.36
      0.89). CONCLUSION: Coffee may protect against Type I EC in obese postmenopausal
      women.

PMID- 24022185
TI  - Does comorbidity interact with colorectal cancer to increase mortality? A
      nationwide population-based cohort study.
AB  - BACKGROUND: It is unknown whether comorbidity interacts with colorectal cancer
      (CRC) to increase the rate of mortality beyond that explained by the independent
      effects of CRC and comorbid conditions. METHODS: We conducted a cohort study
      (1995-2010) of all Danish CRC patients (n=56963), and five times as many persons
      from the general population (n=271670) matched by age, gender, and specific
      comorbidities. To analyse comorbidity, we used the Charlson Comorbidity Index
      (CCI) scores. We estimated standardised mortality rates per 1000 person-years,
      and calculated interaction contrasts as a measure of the excess mortality rate
      not explained by the independent effects of CRC or comorbidities. RESULTS: Among
      CRC patients with a CCI score=1, the 0-1 year mortality rate was 415 out of 1000
      person-years (95% confidence interval (CI): 401, 430) and the interaction
      accounted for 9.3% of this rate (interaction contrast=39 out of 1000 person
      years, 95% CI: 22, 55). For patients with a CCI score of 4 or more, the
      interaction accounted for 34% of the mortality (interaction contrast=262 out of
      1000 person-years, 95% CI: 215, 310). The interaction between CRC and
      comorbidities had limited influence on mortality beyond 1 year after diagnosis.
      CONCLUSION: Successful treatment of the comorbidity is pivotal and may reduce the
      mortality attributable to comorbidity itself, and also the mortality attributable
      to the interaction.

PMID- 24022187
TI  - Trabectedin is a feasible treatment for soft tissue sarcoma patients regardless
      of patient age: a retrospective pooled analysis of five phase II trials.
AB  - BACKGROUND: This retrospective pooled analysis assessed the effect of age on the
      efficacy and safety of trabectedin in young and elderly patients with recurrent
      advanced soft tissue sarcoma (STS). METHODS: Data from 350 adults with STS
      treated in five phase II trials with trabectedin were divided in the younger (<60
      years; n=267) and the older cohort (>=60 years; n=83). RESULTS: The response rate
      did not differ with age (younger: 10.1% vs elderly 9.6%). No significant
      differences were found in median progression-free survival (PFS) in younger (2.5
      months) and older (3.7 months) cohort with a comparable PFS rates at 3 (45.1% vs
      55.1%) and 6 months (29.5% vs 36.4%). Similar median overall survival was
      observed in both cohorts (13.0 vs 14.0 months). Reversible neutropenia and
      aspartate aminotransferase/alanine aminotransferase elevation were the most
      common abnormalities. A higher incidence of grade 3/4 neutropenia (43.6% vs
      60.2%) and fatigue (6.3% vs 14.4%) was observed in older patients. In 24 patients
      aged >=70 years, no significant differences in efficacy or safety outcomes were
      found. CONCLUSION: This analysis demonstrated that trabectedin is a feasible
      treatment in young and elderly patients with STS, with meaningful clinical
      benefits and an acceptable safety profile, essential in palliative treatment of
      elderly patients.

PMID- 24022186
TI  - The clinical implication of SS18-SSX fusion gene in synovial sarcoma.
AB  - BACKGROUND: The aim of this study is to evaluate distribution and clinical impact
      of the SS18-SSX fusion gene in patients with synovial sarcoma in China. METHODS:
      We collected and analysed the clinical data of 88 patients using univariate and
      multivariate survival analysis. HEK 293T and NIH 3T3 cell lines were transfected
      with the SS18-SSX1 or SS18-SSX2 gene to determine the respective involvement of
      these fusion genes in cell proliferation and invasion. RESULTS: Overall survival
      was significantly better among SS18-SSX2 cases (P=0.001), FNCLCC grade 2 cases
      (P<0.001), and UICC stage 1 or 2 (P<0.001) by univariate and multivariate
      survival analysis. SS18-SSX1-positive cells were more proliferative and invasive
      than SS18-SSX2-positive cells. CONCLUSION: SS18-SSX fusion type is a significant
      prognostic factor for patients with synovial sarcoma.

PMID- 24022188
TI  - The association between different night shiftwork factors and breast cancer: a
      case-control study.
AB  - BACKGROUND: Research on the possible association between shiftwork and breast
      cancer is complicated because there are many different shiftwork factors, which
      might be involved including: light at night, phase shift, sleep disruption and
      changes in lifestyle factors while on shiftwork (diet, physical activity, alcohol
      intake and low sun exposure). METHODS: We conducted a population-based case
      control study in Western Australia from 2009 to 2011 with 1205 incident breast
      cancer cases and 1789 frequency age-matched controls. A self-administered
      questionnaire was used to collect demographic, reproductive, and lifestyle
      factors and lifetime occupational history and a telephone interview was used to
      obtain further details about the shiftwork factors listed above. RESULTS: A small
      increase in risk was suggested for those ever doing the graveyard shift (work
      between midnight and 0500 hours) and breast cancer (odds ratio (OR)=1.16, 95%
      confidence interval (CI)=0.97-1.39). For phase shift, we found a 22% increase in
      breast cancer risk (OR=1.22, 95% CI=1.01-1.47) with a statistically significant
      dose-response relationship (P=0.04). For the other shiftwork factors, risks were
      marginally elevated and not statistically significant. CONCLUSION: We found some
      evidence that some of the factors involved in shiftwork may be associated with
      breast cancer but the ORs were low and there were inconsistencies in duration and
      dose-response relationships.

PMID- 24022189
TI  - Higher capecitabine AUC in elderly patients with advanced colorectal cancer
      (SWOGS0030).
AB  - BACKGROUND: The aging process is accompanied by physiological changes including
      reduced glomerular filtration and hepatic function, as well as changes in gastric
      secretions. To investigate what effect would aging have on the disposition of
      capecitabine and its metabolites, the pharmacokinetics between patients >=70
      years and <60 years were compared in SWOG0030. METHODS: Twenty-nine unresectable
      colorectal cancer patients were stratified to either >=70 or <60 years of age,
      where the disposition of capecitabine and its metabolites were compared. RESULTS:
      Notable increase in capecitabine area under the curve (AUC) was accompanied by
      reduction in capecitabine clearance in >=70 years patients (P<0.05). No
      difference in 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine (DFUR), and 5
      fluorouracil (5FU) AUCs between the two age groups, suggesting that
      carboxylesterase and cytidine deaminase (CDA) activity was similar between the
      two age groups. These results suggest that metabolic enzymes involved in
      converting capecitabine metabolites are not altered by age. An elevation in
      capecitabine Cmax and reduction in clearance was seen in females, where
      capecitabine AUC was 40.3% higher in women. Elevation of DFUR Cmax (45%) and AUC
      (46%) (P<0.05) was also noted, suggesting that CDA activity may be higher in
      females. CONCLUSION: Increases in capecitabine Cmax and AUC was observed in
      patients >=70 years when compared with younger patients who were >60 years.

PMID- 24022190
TI  - Long non-coding RNA HOTAIR, a driver of malignancy, predicts negative prognosis
      and exhibits oncogenic activity in oesophageal squamous cell carcinoma.
AB  - BACKGROUND: HOX transcript antisense RNA (HOTAIR), which is expressed from the
      homebox C gene (HOXC) locus, is capable of reprogramming chromatin organisation
      and promoting cancer cell metastasis and can simultaneously bind the polycomb
      repressive complex 2, which enhances H3K27 trimethylation, and the LSD1-CoREST
      REST complex, which is critical for H3K4 demethylation. Clinically, the
      overexpression of HOTAIR is a powerful predictor of the tumour progression and
      overall survival in patients with diverse cancers. The relationship between
      HOTAIR and oesophageal squamous cell carcinoma (ESCC), however, remains unclear.
      We investigated the role of HOTAIR in the pathogenesis of ESCC. METHODS: We used
      quantitative real-time PCR to determine the level of HOTAIR in ESCC cell lines
      and 100 ESCC samples from patients; 56 adjacent non-neoplastic tissues were used
      as controls. We measured the effect of HOTAIR knockdown and overexpression in
      ESCC cell lines using colony formation assays, anchorage-independent growth
      assays, the CCK-8 assay, transwell migration and invasion assays, and Annexin V
      binding assays. We analysed the growth of ESCC xenograft tumours in nude mice.
      Changes in the gene expression and methylation levels in ESCC cell lines were
      analysed using gene expression microarrays and the Infinium HumanMethylation450K
      BeadChip assay, respectively. results: The levels of HOTAIR were increased in
      ESCC cell lines and patient samples compared with the controls; the expression
      levels correlated with the disease stage and survival time. The knockdown of
      HOTAIR in the KYSE510 and KYSE180 ESCC cell lines using small hairpin RNAs
      (shRNAs) reduced the ability of the cells to form foci, migrate, and invade the
      extracellular matrix in culture, altered cell cycle progression, and increased
      the sensitivity of the cells to apoptosis. The HOTAIR knockdown reduced cancer
      cell metastasis in vivo, and the tumours formed by HOTAIR-silenced ESCC cells
      were smaller, both in size and weight, than the tumours and metastases formed by
      the shRNA vector control cells in a mouse xenograft model. The results of the
      gene microarray study showed that HOTAIR reprogrammed the gene expression profile
      of ESCC cells, and the gene ontology analysis revealed an enrichment in genes
      that are important for tumorigenesis, such as genes involved in cell migration
      and the regulation of the cell cycle. Comparing the gene expression profiles and
      DNA methylation analysis between the KYSE180 and KYSE180_HOTAIR cells revealed
      that only a small proportion of the methylation changes were correlated with gene
      expression changes. CONCLUSION: HOX transcript antisense RNA is upregulated in
      ESCC cell lines and patient samples, and promotes ESCC cell proliferation and
      tumour metastasis in mice. The knockdown of HOTAIR resulted in significant
      changes in gene expression, and data analysis suggested that HOTAIR-mediated gene
      regulation has a critical role in ESCC progression and is a novel epigenetic
      molecular target for treating ESCC patients.

PMID- 24022191
TI  - A phase 1 trial of imatinib, bevacizumab, and metronomic cyclophosphamide in
      advanced colorectal cancer.
AB  - BACKGROUND: This phase 1 clinical trial was conducted to determine the safety,
      maximum-tolerated dose (MTD), and pharmacokinetics of imatinib, bevacizumab, and
      metronomic cyclophosphamide in patients with advanced colorectal cancer (CRC).
      METHODS: Patients with refractory stage IV CRC were treated with bevacizumab 5 mg
      kg(-1) i.v. every 2 weeks (fixed dose) plus oral cyclophosphamide q.d. and
      imatinib q.d. or b.i.d. in 28-day cycles with 3+3 dose escalation. Response was
      assessed every two cycles. Pharmacokinetics of imatinib and cyclophosphamide and
      circulating tumour, endothelial, and immune cell subsets were measured. RESULTS:
      Thirty-five patients were enrolled. Maximum-tolerated doses were cyclophosphamide
      50 mg q.d., imatinib 400 mg q.d., and bevacizumab 5 mg kg(-1) i.v. every 2 weeks.
      Dose-limiting toxicities (DLTs) included nausea/vomiting, neutropaenia,
      hyponatraemia, fistula, and haematuria. The DLT window required expansion to 42
      days (1.5 cycles) to capture delayed toxicities. Imatinib exposure increased
      insignificantly after adding cyclophosphamide. Seven patients (20%) experienced
      stable disease for >6 months. Circulating tumour, endothelial, or immune cells
      were not associated with progression-free survival. CONCLUSION: The combination
      of metronomic cyclophosphamide, imatinib, and bevacizumab is safe and tolerable
      without significant drug interactions. A subset of patients experienced prolonged
      stable disease independent of dose level.

PMID- 24022193
TI  - Prognostic value of ABO blood group in southern Chinese patients with established
      nasopharyngeal carcinoma.
AB  - BACKGROUND: ABO blood group is associated with aetiology of nasopharyngeal
      carcinoma (NPC); however, the effect of it on survival of patients diagnosed with
      NPC has not been explored. METHODS: We retrospectively analysed two cohorts of
      southern Chinese patients with WHO histological type III: intensity-modulated
      radiotherapy (IMRT) cohort, 924 patients; and conventional radiotherapy (CRT)
      cohort, 1193 patients. Associations of ABO blood group with survival were
      estimated using Cox regression. RESULTS: In IMRT cohort, we observed significant
      associations of blood type A with overall survival (OS) and distant metastasis
      free survival (DMFS), compared with type O, after adjusting for prognostic
      factors. Compared with non-A blood types (B, AB, and O), type A patients had
      significantly lower OS and DMFS (adjusted hazard ratio (HR)=1.49, 95% CI 1.03
      2.17, P=0.036; HR=1.68, 95% CI 1.13-2.51, P=0.011, respectively); similar results
      were obtained in CRT cohort. Subgroup analyses of the entire population showed
      that lower OS conferred by blood type A was not significantly modified by age,
      smoking status, drinking status, immunoglobulin A against Epstein-Barr virus
      viral capsid antigen (VCA-IgA) titre, or chemotherapy; however, lower OS was not
      observed in female patients or patients with early clinical stage disease.
      CONCLUSION: ABO blood group is associated with survival in NPC; patients with
      blood type A had significantly lower OS and DMFS than patients with non-A blood
      types.

PMID- 24022192
TI  - The in situ local immune response, tumour senescence and proliferation in
      colorectal cancer.
AB  - BACKGROUND: Immune cell infiltrates are important determinants of colorectal
      cancer (CRC) outcome. Their presence may be driven by tumour or host-specific
      factors. From previous studies in mice, senescence, a state of cell cycle arrest,
      may moderate tumour progression through upregulation of antitumour immune
      responses. The relationships between senescence and immune infiltrates have not
      previously been studied in humans. We explore whether a marker of senescence
      (p16(ink4a)) in combination with low level expression of a proliferation marker
      (ki-67) relate to T cell infiltrates in CRC, and whether p16(ink4a), Ki-67 and
      immune infiltrates have similar prognostic value. METHODS: Immunostaining of
      p16(inka) and Ki-67 was performed within a CRC tissue microarray. Nuclear
      p16(inka) and Ki-67 were categorised as high/low. T-cell markers, CD3, CD45RO,
      CD8 and FOXP3 were scored separately as high/low grade in three areas of the
      tumour: the invasive margin (IM), tumour stroma and cancer cell nests (CCNs).
      results: Two hundred and thirty stage I-III cancers were studied. High nuclear
      p16(ink4a) was expressed in 63% and high proliferation (Ki-67 >15%) in 61%.
      p16(ink4a) expression was associated with reduced CD45RO+ cells at the IM
      (P<0.05) and within the stroma (P<0.05) and reduced CD8+ cells at the IM
      (P<0.01). A low Ki-67 proliferative index was associated with reduced density of
      CD3+ cells in CCNs (P<0.01), reduced CD45RO+ cells at the IM (P<0.05) and within
      the CCNs (P<0.001), reduced FOXP3+ cells at the IM (P<0.001), within the stroma
      (P=0.001) and within CCNs (P<0.001) and reduced CD8+ cells at the IM (P<0.05) and
      within the CCNs (P<0.05). Tumours with both a low proliferative index and
      expression of p16(ink4a) demonstrated similar consistent relationships with
      reduced densities of T-cell infiltrates. On multivariate analysis, TNM stage
      (P<0.001), low CD3 cells at the IM (P=0.014), low CD8 cells at the IM (P=0.037),
      low proliferation (Ki-67; P=0.013) and low senescence (p16(ink4a); P=0.002) were
      independently associated with poorer cancer survival. CONCLUSION: Senescence,
      proliferation and immune cell infiltrates are independent prognostic factors in
      CRC. Although related to survival, p16(ink4a)-associated senescence is not
      associated with an upregulation of antitumour T-cell responses.

PMID- 24022194
TI  - Prognosis in HIV-infected patients with non-small cell lung cancer.
AB  - BACKGROUND: We conducted a population-based study to evaluate whether non-small
      cell lung cancer (NSCLC) prognosis was worse in HIV-infected compared with HIV
      uninfected patients. METHODS: Using the Surveillance, Epidemiology and End
      Results (SEER) registry linked to Medicare claims, we identified 267 HIV-infected
      patients and 1428 similar controls with no evidence of HIV diagnosed with NSCLC
      between 1996 and 2007. We used conditional probability function (CPF) analyses to
      compare survival by HIV status accounting for an increased risk of non-lung
      cancer death (competing risks) in HIV-infected patients. We used multivariable
      CPF regression to evaluate lung cancer prognosis by HIV status adjusted for
      confounders. RESULTS: Stage at presentation and use of stage-appropriate lung
      cancer treatment did not differ by HIV status. Median survival was 6 months (95%
      confidence interval (CI): 5-8 months) among HIV-infected NSCLC patients compared
      with 20 months (95% CI: 17-23 months) in patients without evidence of HIV.
      Multivariable CPF regression showed that HIV was associated with a greater risk
      of lung cancer-specific death after controlling for confounders and competing
      risks. CONCLUSION: NSCLC patients with HIV have a poorer prognosis than patients
      without evidence of HIV. NSCLC may exhibit more aggressive behaviour in the
      setting of HIV.

PMID- 24022196
TI  - Targeting EGFR and PI3K pathways in ovarian cancer.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) is expressed in ovarian
      cancer, but agents targeting this pathway have shown little effect as single
      agents. This may be due to the presence of alternative pathways, particularly
      activation of the PI3K/Akt/MTOR pathway. METHODS: We have therefore examined the
      effect of inhibitors of this pathway (ZSTK474 and sirolimus) in combination with
      the EGFR inhibitors erlotinib and gefitinib in ovarian cancer primary cell
      cultures. RESULTS: The single-agent EGFR inhibitors showed little activity,
      although some activity was seen with the single-agent PI3K inhibitor, ZSTK474.
      Combinations of ZSTK474 with EGFR inhibitors showed enhanced activity with some
      evidence of synergy, whereas sirolimus combinations were less active. The results
      were not explicable on the basis of PIK3CA mutation or amplification, or PTEN
      loss, although one tumour with a KRAS mutation showed resistance to EGFR
      inhibitors. However, there was correlation of the EGFR expression with
      sensitivity to EGFR and resistance to PI3K active agents, and inverse correlation
      in the sensitivity of individual tumours to agents active against these pathways,
      suggesting a mechanism of action for the combination. CONCLUSION: Phase I/II
      clinical trials with these agents should include further pharmacodynamic
      endpoints and molecular characterisation to identify patients most likely to
      benefit from this strategy.

PMID- 24022195
TI  - Presence of the coxsackievirus and adenovirus receptor (CAR) in human neoplasms:
      a multitumour array analysis.
AB  - BACKGROUND: The Coxsackie- and Adenovirus Receptor (CAR) has been assigned two
      crucial attributes in carcinomas: (a) involvement in the regulation of growth and
      dissemination and (b) binding for potentially therapeutic adenoviruses. However,
      data on CAR expression in cancer types are conflicting and several entities have
      not been analysed to date. METHODS: The expression of CAR was assessed by
      immunohistochemical staining of tissue microarrays (TMA) containing 3714
      specimens derived from 100 malignancies and from 273 normal control tissues.
      RESULTS: The expression of CAR was detected in all normal organs, except in the
      brain. Expression levels, however, displayed a broad range from being barely
      detectable (for example, in the thymus) to high abundance expression (for
      example, in the liver and gastric mucosa). In malignancies, a high degree of
      variability was notable also, ranging from significantly elevated CAR expression
      (for example, in early stages of malignant transformation and several tumours of
      the female reproductive system) to decreased CAR expression (for example, in
      colon and prostate cancer types). CONCLUSION: Our results provide a comprehensive
      insight into CAR expression in neoplasms and indicate that CAR may offer a
      valuable target for adenovirus-based therapy in a subset of carcinomas.
      Furthermore, these data suggest that CAR may contribute to carcinogenesis in an
      entity-dependent manner.

PMID- 24022197
TI  - Solid cancer incidence other than lung, liver and bone in Mayak workers: 1948
      2004.
AB  - BACKGROUND: Cancer incidence in the Mayak Production Association (PA) cohort was
      analysed to investigate for the first time whether external gamma-ray and
      internal plutonium exposure are associated with raised incidence of solid cancers
      other than lung, liver and bone (other solid cancers). METHODS: The cohort
      includes 22,366 workers of both sexes who were first employed between 1948 and
      1982. A total of 1447 cases of other solid cancers were registered in the follow
      up period until 2004. The Poisson regression was used to estimate the excess
      relative risk (ERR) per unit of cumulative exposure to plutonium and external
      gamma-ray. RESULTS: A weak association was found between cumulative exposure to
      external gamma-ray and the incidence of other solid cancers (ERR/Gy=0.07; 95%
      confidence intervals (CIs): 0.01-0.15), but this association lost its
      significance after adjusting for internal plutonium exposure. There was no
      indication of any association with plutonium exposure for other solid cancers.
      Among 16 individual cancer sites, there was a statistically significant
      association with external exposure for lip cancer (ERR/Gy=1.74; 95% CI: 0.37;
      6.71) and with plutonium exposure for pancreatic cancer (ERR/Gy=1.58; 95% CI;
      0.17; 4.77). CONCLUSION: This study of Mayak workers does not provide evidence of
      an increased risk of other solid cancers. The observed increase in the risk of
      cancer of the lip and pancreas should be treated with caution because of the
      limited amount of relevant data and because the observations may be simply due to
      chance.

PMID- 24022199
TI  - Nuclear double-fluorescent reporter for in vivo and ex vivo analyses of
      biological transitions in mouse nuclei.
AB  - Cre-responsive dual-fluorescent alleles allow in situ marking of cell lineages or
      genetically modified cells. Here we report a dual-fluorescent allele, ROSA nT-nG
      , which directs nuclear accumulation of tdTomato in Cre-naive lineages. Cre
      converts the allele to ROSA nG , which drives nuclear EGFP accumulation.
      Conditions were established for analyzing marked nuclei by flow cytometry on the
      basis of red-green fluorescence and ploidy, with a particular focus on liver
      nuclei. Hydrodynamic delivery of a Cre-expression plasmid was used to time-stamp
      arbitrary hepatocytes for lineage tracing. The distinct green fluorescence of
      nuclei from Cre-exposed lineages facilitated analyses of ploidy transitions
      within clones. To assess developmental transitions in liver nuclei, ROSA nT-nG
      was combined with the hepatocyte-specific AlbCre transgene, facilitating
      discrimination between hepatocyte and nonhepatocyte nuclei. Nuclei extracted from
      postnatal day 2 (P2) livers were 41 % green and 59 % red and reached a stable
      level of 84 % green by P22. Until P20, green nuclei were >98 % diploid (2N); at
      P40 they were ~56 % 2N, 43 % 4N, and <1 % 8N; and by P70 they reached a stable
      distribution of ~46 % 2N, 45 % 4N, and 9 % 8N. In conclusion, ROSA nT-nG will
      facilitate in vivo and ex vivo studies on liver and will likely be valuable for
      studies on tissues like muscle, kidney, or brain in which cells are refractory to
      whole-cell flow cytometry, or like trophectoderm derivatives or cancers in which
      cells undergo ploidy transitions.

PMID- 24022198
TI  - Identification of QTLs for seed and pod traits in soybean and analysis for
      additive effects and epistatic effects of QTLs among multiple environments.
AB  - Soybean seed and pod traits are important yield components. Selection for high
      yield style in seed and pod along with agronomic traits is a goal of many soybean
      breeders. The intention of this study was to identify quantitative trait loci
      (QTL) underlying seed and pod traits in soybean among eleven environments in
      China. 147 recombinant inbred lines were advanced through single-seed-descent
      method. The population was derived from a cross between Charleston (an American
      high yield soybean cultivar) and DongNong594 (a Chinese high yield soybean
      cultivar). A total of 157 polymorphic simple sequence repeat markers were used to
      construct a genetic linkage map. The phenotypic data of seed and pod traits
      [number of one-seed pod, number of two-seed pod, number of three-seed pod, number
      of four-seed pod, number of (two plus three)-seed pod, number of (three plus
      four)-seed pod, seed weight per plant, number of pod per plant] were recorded in
      eleven environments. In the analysis of single environment, fourteen main effect
      QTLs were identified. In the conjoint analysis of multiple environments, twenty
      four additive QTLs were identified, and additive QTLs by environments
      interactions (AE) were evaluated and analyzed at the same time among eleven
      environments; twenty-three pairs of epistatic QTLs were identified, and epistasis
      (additive by additive) by environments interactions (AAE) were also analyzed and
      evaluated among eleven environments. Comparing the results of identification
      between single environment mapping and multiple environments conjoint mapping,
      three main effect QTLs with positive additive values and another three main
      effect QTLs with negative additive values, had no interactions with all
      environments, supported that these QTLs could be used in molecular assistant
      breeding in the future. These different effect QTLs could supply a good
      foundation to the gene clone and molecular asisstant breeding of soybean seed and
      pod traits.

PMID- 24022200
TI  - Ecscr regulates insulin sensitivity and predisposition to obesity by modulating
      endothelial cell functions.
AB  - Insulin resistance is closely associated with obesity and is one of the earliest
      symptoms of type-2 diabetes. Endothelial cells are involved in the pathogenesis
      of insulin resistance through their role in insulin delivery and adipose tissue
      angiogenesis. Here we show that Ecscr (endothelial cell surface expressed
      chemotaxis and apoptosis regulator; also known as ARIA), the transmembrane
      protein that regulates endothelial cell signalling, is highly expressed in white
      and brown adipose tissues, and regulates energy metabolism and glucose
      homeostasis by modulating endothelial cell functions. Ecscr-deficient mice fed a
      normal chow show improved glucose tolerance and enhanced insulin sensitivity. We
      demonstrate that Ecscr deletion enhances the insulin-mediated Akt/endothelial
      nitric oxide synthase activation in endothelial cells, which increases insulin
      delivery into the skeletal muscle. Ecscr deletion also protects mice on a high
      fat diet from obesity and obesity-related metabolic disorders by enhancing
      adipose tissue angiogenesis. Conversely, targeted activation of Ecscr in
      endothelial cells impairs glucose tolerance and predisposes mice to diet-induced
      obesity. Our results suggest that the inactivation of Ecscr enhances insulin
      sensitivity and may represent a new therapeutic strategy for treating metabolic
      syndrome. 

PMID- 24022201
TI  - [Empirical antibiotic therapy in intra-abdomial infections: cases and evidence
      based therapeutic recommendations].
AB  - Intra-abdominal infections (IAI) are a common problem in visceral medicine. In
      Germany more than 150 000 patients are treated each year for IAI with courses
      ranging from uncomplicated disease to severe life-threatening manifestations. IAI
      represent the second most common cause of septic shock and the second most common
      cause of infection-related mortality in intensive care. Due to increasing
      antimicrobial resistance, changes in pathogen spectra and increasing patient co
      morbidities, recommendations for empirical antibiotic therapy have to be
      continuously updated: Whereas inadequate empirical treatment is associated with
      poor prognosis, unselected broad-spectrum therapy may increase antimicrobial
      resistances. Illustrated by clinical cases of typical intra-abdominal infections,
      this article reviews recommendations for antibiotic therapy based on national and
      international guidelines under consideration of local resistance rates and
      patient-specific factors to provide a basis for improved therapy of this common
      problem. 

PMID- 24022202
TI  - Endoscopic sedation and monitoring practice in Germany: re-evaluation from the
      first nationwide survey 3 years after the implementation of an evidence and
      consent based national guideline.
AB  - BACKGROUND AND STUDY AIMS: The use of sedation (e. g., of short-acting propofol)
      for gastrointestinal endoscopy has shown an upward trend in the USA and Europe
      over the last decade. To improve patient's safety different nationwide guidelines
      have been developed. This survey aimed at providing nationwide re-evaluated data
      3 years after the implementation of consent- and evidence-based national
      guideline on sedation for gastrointestinal endoscopy. METHODS: A 24-item survey
      regarding current practices of endoscopy, sedation and monitoring in
      gastrointestinal endoscopy was sent to 4 405 members of the German Society of
      Digestive and Metabolic Diseases (DGVS). RESULTS: A total of 741/4405 (17 %)
      questionnaires were returned. Compared to 2007 we documented a further increase
      of the use of sedation during the performance of esophagogastro-duodenoscopies
      (EGDs) (82 vs. 74 % in 2007) and colonoscopies (91 vs. 87 % in 2007), accompanied
      with an increased rate of using propofol as a sedative agent in 97 vs. 74 % of
      the cases in 2007. In contrast the use of midazolam substantially decreased to 69
      % versus 82 % in 2007. Most commonly used sedation regimens are still propofol +/
      benzodiazepines (43 vs. 38 % in 2007), while a combination of midazolam +/-
      opioid decreased to 15 % versus 35 % in 2007. Unchanged to data from 2007,
      patients were routinely monitored by pulse oximetry (99 %). Routine use of an
      automated blood pressure monitoring increased to 40 % (versus 29 % in 2007) and
      the use of electrocardiography monitoring nearly doubled to 24 vs. 13 % in 2007.
      Supplemental oxygen is nowadays routinely administered in 64 % compared to 34 %
      of the cases in 2007. Regarding the administration of sedation we observed a
      profound increase of nurse-administered propofol sedation (NAPS; 73 % in 2011, 39
      % in 2007) with a decrease of endoscopist-directed propofol sedation (29 % in
      2011 vs. 59 % in 2007). However, monitored anaesthesia care was still only rarely
      used in Germany (2 %). CONCLUSION: After the implementation of the first national
      sedation guideline the use of propofol has become the most popular sedation
      regime in Germany, mainly administered as NAPS by trained nurses as a standard
      procedure. Automated blood pressure measurements and ECG recording were more
      often implemented in the monitoring practice and also the routine use of
      supplemental oxygen has been clearly improved.

PMID- 24022203
TI  - Echinococcosis mimicking autoimmune or malignant bile duct disease.
AB  - Indeterminate strictures of the bile ducts are common diagnostic dilemmas in
      gastroenterology, and differential diagnosis includes inflammatory and neoplastic
      diseases. Alveolar echinococcosis (AE) is rarely considered as a differential
      diagnosis, although it is endemic in the Northern hemisphere. In this case report
      on a 50-year-old male patient, the lack of cystic lesions or calcifications on
      CT, and suggestive ERCP findings made a hilar cholangiocellular carcinoma the
      most probable differential diagnosis, and only explorative laparotomy provided
      the definite diagnosis of AE. AE should therefore be included in the differential
      diagnosis of indeterminate biliary strictures even in the absence of typical
      stigmata in imaging studies. 

PMID- 24022204
TI  - [Radiofrequency ablation effectively treats chronic radiation proctitis].
AB  - Chronic radiation proctitis can develop after radiation therapy of pelvic
      malignancies. Symptoms include haematochezia, diarrhoea, tenesmus, urgency,
      faecal incontinence, and rectal pain. Various therapies have been attempted with
      argon plasma coagulation (APC) currently being the treatment of choice, but
      complications such as ulceration and stricture are commonly encountered. There
      are limited data suggesting that radiofrequency ablation (RFA) may be an
      effective alternative to APC, in particular in transfusion-dependent patients.
      Here we report two cases of chronic radiation proctitis, one of whom was
      transfusion-dependent, who were safely and successfully treated with focal RFA.
      Haematochezia decreased significantly the day subsequent to treatment, and
      transfusion independence was achieved after a single session. Three to four
      sessions were required to eradicate the neovascular lesions. Post-therapeutic
      rectal re-epithelialisation occurred, and no bleeding was encountered during up
      to nine months of follow-up. 

PMID- 24022205
TI  - Primary perivascular epitheloid cell tumour (PEComa) of the liver: case report
      and review of the literature.
AB  - PURPOSE: Perivascular epitheloid cell tumour [PEComa] is a rare neoplasm entity,
      characterized by perivascular epitheloid cells with a coexpression of smooth
      muscle and melanocytic markers. PEComas are found in a variety of localizations,
      though lesions within the liver are still scarcely found. Although the majority
      of these tumours are recognized as benign, there are some reports about advanced
      and aggressive tumours even with fatal outcome. By means of this case report and
      literary review including other 21 published cases, potential treatment
      modalities concerning clinical diagnostics, therapy and the follow-up care should
      be discussed. METHODS: The following report presents the case of a 53-year old
      woman with a known liver lesion, since four years under regularly sonographic
      controls. Finally, after a haemorrhage episode, the lesion was resected and the
      diagnosis found. For the literary review a systematic search for case reports
      published between January 1, 1999 and May 1, 2012 was performed on Pubmed.
      RESULTS: The only way, till now, of confirming the diagnosis is through
      immunohistochemical examinations. The already published Malignancy criteria by
      Folpe et al. must be taken carefully in question, as there are cases of malignant
      behaviour, that do not exactly coincide with these. CONCLUSION: Primary PEComa of
      the liver must be treated as potential malignant and therefore a close follow-up
      is demanded.

PMID- 24022206
TI  - [Sofosbuvir for hepatitis C - is brevity the soul of wit?].

PMID- 24022208
TI  - Solar-blind photodetectors for harsh electronics.
AB  - We demonstrate solar-blind photodetectors (PDs) by employing AlN thin films on
      Si(100) substrates with excellent temperature tolerance and radiation hardness.
      Even at a bias higher than 200 V the AlN PDs on Si show a dark current as low as
      ~ 1 nA. The working temperature is up to 300 degrees C and the radiation
      tolerance is up to 10(13) cm(-2) of 2-MeV proton fluences for AlN metal
      semiconductor-metal (MSM) PDs. Moreover, the AlN PDs show a photoresponse time as
      fast as ~ 110 ms (the rise time) and ~ 80 ms (the fall time) at 5 V bias. The
      results demonstrate that AlN MSM PDs hold high potential in next-generation deep
      ultraviolet PDs for use in harsh environments. 

PMID- 24022207
TI  - Antiplatelet therapy in patients undergoing percutaneous coronary intervention:
      economic considerations.
AB  - Percutaneous coronary intervention (PCI) is one of the most common medical
      procedures performed for treatment of coronary artery disease. Antiplatelet
      medications as adjunctive therapy for PCI are used routinely, with indications
      for specific agents or their combinations varying depending on the clinical
      scenario. While the cost-effectiveness of well-established agents has been
      extensively studied, newer drugs have not been evaluated as thoroughly. In
      addition, the clinical application of some antiplatelet drugs has recently
      changed, thus making older studies of cost effectiveness less applicable to the
      current landscape of clinical practice. This article reviews cost-effectiveness
      considerations of antiplatelet therapies in the treatment of coronary artery
      disease in patients undergoing PCI. Aspirin, P2Y12 inhibitors including
      clopidogrel and the newer agents prasugrel and ticagrelor, as well as
      glycoprotein (GP) IIb/IIIa inhibitors, are discussed. Overall, the use of dual
      antiplatelet therapy with aspirin and a P2Y12 inhibitor in patients undergoing
      PCI improves ischaemic outcomes and appears to be cost effective. The few
      available studies suggest that the recently approved medications prasugrel and
      ticagrelor are cost-effective alternatives to clopidogrel. However, no direct
      comparison between these two newer agents is available. The indications for GP
      IIb/IIIa inhibitors have changed in the current PCI era, and there is a paucity
      of cost-effectiveness data for their use in contemporary care.

PMID- 24022209
TI  - Quantitative kinetic investigation on transmetalation of ArZnX in a Pd-catalysed
      oxidative coupling.
AB  - Transmetalation is the rate-limiting step. [R-Pd-Ar] was suggested to be the
      resting species from the kinetic studies. Quantitative measurement of the
      transmetalation of ArZnCl with [R-Pd-Ar] from a live Pd-catalysed oxidative
      coupling reaction was conducted and the corresponding activation enthalpy was
      determined as 12.3 kcal mol(-1). 

PMID- 24022211
TI  - The anticipatory proportion as an indicator of language impairment in early-stage
      cognitive disorder in the elderly.
AB  - BACKGROUND: The anticipatory proportion (AP), the ratio between perseverative and
      anticipatory speech errors, is reduced in patients with brain injury. However, it
      is unknown whether the AP is also reduced in elderly speakers with cognitive
      impairment. METHODS: 20 elderly speakers with a Mini Mental State Examination
      (MMSE) score of 25-27 and 20 elderly speakers with an MMSE score of 28-30 were
      assessed using a tongue-twister-based speech test, the Regensburg Word Fluency
      Test (RWT) and an object naming test. RESULTS: The AP in the group of speakers
      with an MMSE score of 25-27 was significantly lower. Accordingly, the AP and
      scores in the RWT and the object naming test were higher in persons with an MMSE
      score of 28-30. CONCLUSION: Language alterations in mild cognitive dysfunction
      are detectable with the AP. Further longitudinal studies are needed to evaluate
      the predictive value of the AP.

PMID- 24022212
TI  - Evidence for the formation of a metal alkyl intermediate in the zinc mediated
      intramolecular hydroamination.
AB  - A diketiminato zinc amide complex, LZnNMe2 (1) [L = CH{(CMe)2(2,6
      (i)Pr2C6H3N)2}], was prepared and investigated for the catalytic hydroamination
      of 2,2-dimethylpent-4-en-1-amine. The reaction with the amino olefin resulted in
      a transamination reaction and the subsequent insertion of the olefin moiety into
      the metal-amide bond. However, the reaction stopped at this point providing
      access to the metal alkyl intermediate, LZnR (R = N[upper bond 1 start]H-CH2-CPh2
      CH2-C[upper bond 1 end]H-) (2). The isolation of this primary insertion product
      further strengthens the widely accepted mechanism for the intramolecular
      hydroamination.

PMID- 24022213
TI  - p19(INK4d) mRNA and protein expression as new prognostic factors in ovarian
      cancer patients.
AB  - p19(INK4d) (CDKN2D) is a negative regulator of the cell cycle. Little is known of
      its role in cancer development and prognosis. We aimed to evaluate the clinical
      significance of p19(INK4d) expression in ovarian carcinomas with respect to the
      TP53 accumulation status, as well as the frequency of CDKN2D mutations.
      p19(INK4d) and TP53 expression was evaluated immunohistochemically in 445 ovarian
      carcinomas: 246 patients were treated with platinum-cyclophosphamide (PC/PAC),
      while 199 were treated with taxane-platinum agents (TP). CDKN2D gene expression
      (mRNA) was examined in 106 carcinomas, while CDKN2D mutations in 68 tumors. Uni-
      and multivariate statistical analyses (logistic regression and the Cox
      proportional hazards model) were performed for patient groups divided according
      to the chemotherapeutic regimen administered, and in subgroups with and without
      TP53 accumulation. High p19(INK4d) expression increased the risk of death, but
      only in patients with the TP53-negative carcinomas (HR 1.61, P = 0.049 for PC/PAC
      treated patients, HR 2.00, P = 0.015 for TP-treated patients). This result was
      confirmed by the mRNA analysis (HR 4.24, P = 0.001 for TP-treated group). High
      p19(INK4d) protein expression associated with adverse clinicopathological
      factors. We found no alterations in the CDKN2D gene; the c.90C>G (p.R30R;
      rs1968445) polymorphism was detected in 10% of tumors. Our results suggest that
      p19(INK4d) expression is a poor prognostic factor in ovarian cancer patients.
      Analyses of tumor groups according to the TP53 accumulation status facilitate the
      identification of cancer biomarkers. 

PMID- 24022214
TI  - Linkage of data from diverse data sources (LDS): a data combination model
      provides clinical data of corresponding specimens in biobanking information
      system.
AB  - To provide sufficient clinical data for corresponding specimens from diverse
      databases established before the implementation of biobanks for research purposes
      with respect to data privacy regulations. For this purpose, we developed a data
      model called "linkage of data from diverse data sources (LDS)". The data model
      was developed to merge clinical data from an existing local database with
      biospecimen repository data in our serum bank for uro-oncology. This concept
      combines two data models based on XML: the first stores information required to
      connect multiple data sources and retrieve clinical data, and the second provides
      a data architecture to acquire clinical and repository data. All data were
      anonymized and encrypted using the Advanced Encryption Standard. X.509
      certificates were applied to secure data access. Furthermore, we tested the
      feasibility of implementing these models in the information management system for
      biobanking. The data concept can provide clinical and repository data of
      biospecimens. Only authorized receivers can access these data. Sensitive and
      personal data are not accessible by the data receivers. The data receiver cannot
      backtrack to the individual donor using the data model. The acquired data can be
      converted into a text file format supported by familiar statistical software.
      Supplementary tools were implemented to generate and view XML documents based on
      these data models. This data model provides an effective approach to distribute
      clinical and repository data from different data sources to enable data analysis
      compliant with data privacy regulations. 

PMID- 24022217
TI  - Minimally invasive reposition of intraarticular calcaneal fractures: a case
      report.
AB  - BACKGROUND: Calcaneal fracture is a most common bony injury of the hindfoot. In
      constitutes 60% of foot fractures and 1-2% of all fractures. According to current
      literature 75% of these fractures involve articular surfaces, which makes them
      especially difficult to treat. Intraarticular fractures often result in permanent
      disability impairing foot function and ambulation, sometimes due to inadequate
      treatment method. According to literature, in developed countries open reduction
      and internal plate fixation is standard treatment of intraarticular calcaneal
      fractures. This treatment poses a risk of impaired wound healing and is
      appropriate for selected group of patients without additional risk factors. Other
      patients are treated with minimally invasive methods. Proponents of minimally
      invasive techniques apply distraction, which makes most intraarticular calcaneal
      fractures amenable to this method. CASE REPORT: This paper presents a minimally
      invasive treatment technique for intraarticular (depression type according to
      Essex-Lopresti, IIA accordind to Sanders) calcaneal fracture in 63-years old man.
      External fixator (Monotube) is used for intraoperative distraction. Posterior
      facet is reduced with additional maneuvers. RESULTS: With this technique we were
      able to reduce posterior faced, correct varus alignment and restore Bohler's
      angle. With restoration of shape of calcaneal bone optimal functional result can
      be expected. At six moths follow-up very good result was observed.

PMID- 24022216
TI  - Does social disadvantage over the life-course account for alcohol and tobacco use
      in Irish people? Birth cohort study.
AB  - AIMS: Few studies have examined how the settlement experiences of migrant parents
      might impact on the downstream adult health of second-generation minority ethnic
      children. We used prospective data to establish if childhood adversity relating
      to the settlement experiences of Irish-born parents might account for downstream
      adverse health-related behaviours in second-generation Irish respondents in
      adulthood. DESIGN, SETTING AND PARTICIPANTS: Cohort data from the National Child
      Development Study, comprising 17 000 births from a single week in 1958, from
      Britain, were analysed. Respondents were followed to mid-life. Dependent
      variables were alcohol and tobacco use. The contribution of life-course
      experiences in accounting for health-related behaviours was examined. FINDINGS:
      Relative to the rest of the cohort, the prevalence of harmful/hazardous alcohol
      use was elevated in early adulthood for second-generation men and women, although
      it reduced by age 42. Second-generation Irish men were more likely to report
      binge alcohol use (odds ratio 1.45; 95% confidence interval 0.99, 2.11; P =
      0.05), and second-generation Irish women were more likely to smoke (odds ratio
      1.67; 95% confidence interval 1.23, 2.23; P = 0.001), at mid-life. Childhood
      disadvantage partially mediated associations between second-generation Irish
      status and mid-life alcohol and tobacco use, although these were modest for
      associations with smoking in Irish women. CONCLUSIONS: The findings suggest
      mechanisms for the intergenerational 'transmission' of health disadvantage in
      migrant groups, across generations. More attention needs to focus on the public
      health legacy of inequalities transferring from one migrant generation to the
      next.

PMID- 24022215
TI  - Tandem combination of Trigonella foenum-graecum defensin (Tfgd2) and Raphanus
      sativus antifungal protein (RsAFP2) generates a more potent antifungal protein.
AB  - Plant defensins are small (45 to 54 amino acids) positively charged antimicrobial
      peptides produced by the plant species, which can inhibit the growth of a broad
      range of fungi at micro-molar concentrations. These basic peptides share a common
      characteristic three-dimensional folding pattern with one alpha-helix and three
      beta-sheets that are stabilized by eight disulfide-linked cysteine residues.
      Instead of using two single-gene constructs, it is beneficial when two effective
      genes are made into a single fusion gene with one promoter and terminator. In
      this approach, we have linked two plant defensins namely Trigonella foenum
      graecum defensin 2 (Tfgd2) and Raphanus sativus antifungal protein 2 (RsAFP2)
      genes by a linker peptide sequence (occurring in the seeds of Impatiens
      balsamina) and made into a single-fusion gene construct. We used pET-32a+ vector
      system to express Tfgd2-RsAFP2 fusion gene with hexahistidine tag in Escherichia
      coli BL21 (DE3) pLysS cells. Induction of these cells with 1 mM IPTG achieved
      expression of the fusion protein. The solubilized His6-tagged recombinant fusion
      protein was purified by immobilized-metal (Ni2+) affinity column chromatography.
      The final yield of the fusion protein was 500 ng/MUL. This method produced
      biologically active recombinant His6-tagged fusion protein, which exhibited
      potent antifungal action towards the plant pathogenic fungi (Botrytis cinerea,
      Fusarium moniliforme, Fusarium oxysporum, Phaeoisariopsis personata and
      Rhizoctonia solani along with an oomycete pathogen Phytophthora parasitica var
      nicotianae) at lower concentrations under in vitro conditions. This strategy of
      combining activity of two defensin genes into a single-fusion gene will
      definitely be a promising utility for biotechnological applications.

PMID- 24022218
TI  - Mapping colitis susceptibility in mouse models: distal chromosome 3 contains
      major loci related to Cdcs1.
AB  - Inflammatory bowel disease (IBD) summarizes a group of chronic intestinal
      disorders with Crohn's disease and ulcerative colitis being most prominent.
      Though much effort is put into identification of causative factors, its etiology
      is still not understood. Risk factors for disease development include genetic
      predisposition and environmental triggers. Crucial for identification and
      analysis of relevant factors are mouse models. Experimental IBD in mice occurs
      spontaneously or is induced by chemicals, cell transfer, pathogens, or genetic
      mutation. These models were utilized for analyzing genetic contribution to
      disease and genotype-environmental interactions. In these studies, a variety of
      modifier loci were identified, thereby demonstrating the complexity of disease. A
      major contribution of distal chromosome 3 was independently replicated in several
      studies. The first colitogenic QTL in this region was detected using the IL-10
      deficient mouse model and called cytokine deficiency-induced colitis
      susceptibility (Cdcs)1. This quantitative trait locus contains at least three
      subintervals with independent genetic factors. This locus or defined subintervals
      were replicated in at least seven studies, using models based on dysregulation of
      innate or adaptive immunity or pathogen control. In this review we illustrate the
      various models used for genetic mapping of susceptibility to experimental IBD and
      display Cdcs1-related loci as well as the mechanism of their contribution
      identified so far. 

PMID- 24022219
TI  - Genome scan for meat quality traits in Nelore beef cattle.
AB  - Meat quality traits are economically important because they affect consumers'
      acceptance, which, in turn, influences the demand for beef. However, selection to
      improve meat quality is limited by the small numbers of animals on which meat
      tenderness can be evaluated due to the cost of performing shear force analysis
      and the resultant damage to the carcass. Genome wide-association studies for
      Warner-Bratzler shear force measured at different times of meat aging, backfat
      thickness, ribeye muscle area, scanning parameters [lightness, redness (a*), and
      yellowness] to ascertain color characteristics of meat and fat, water-holding
      capacity, cooking loss (CL), and muscle pH were conducted using genotype data
      from the Illumina BovineHD BeadChip array to identify quantitative trait loci
      (QTL) in all phenotyped Nelore cattle. Phenotype count for these animals ranged
      from 430 to 536 across traits. Meat quality traits in Nelore are controlled by
      numerous QTL of small effect, except for a small number of large-effect QTL
      identified for a*fat, CL, and pH. Genomic regions harboring these QTL and the
      pathways in which the genes from these regions act appear to differ from those
      identified in taurine cattle for meat quality traits. These results will guide
      future QTL mapping studies and the development of models for the prediction of
      genetic merit to implement genomic selection for meat quality in Nelore cattle. 

PMID- 24022220
TI  - Usher proteins in inner ear structure and function.
AB  - Usher syndrome (USH) is a neurosensory disorder affecting both hearing and vision
      in humans. Linkage studies of families of USH patients, studies in animals, and
      characterization of purified proteins have provided insight into the molecular
      mechanisms of hearing. To date, 11 USH proteins have been identified, and
      evidence suggests that all of them are crucial for the function of the
      mechanosensory cells of the inner ear, the hair cells. Most USH proteins are
      localized to the stereocilia of the hair cells, where mechano-electrical
      transduction (MET) of sound-induced vibrations occurs. Therefore, elucidation of
      the functions of USH proteins in the stereocilia is a prerequisite to
      understanding the exact mechanisms of MET. 

PMID- 24022221
TI  - Targeting the endothelial progenitor cell surface proteome to identify novel
      mechanisms that mediate angiogenic efficacy in a rodent model of vascular
      disease.
AB  - Endothelial progenitor cells (EPCs) promote angiogenesis, and clinical trials
      suggest autologous EPC-based therapy may be effective in treatment of vascular
      diseases. Albeit promising, variability in the efficacy of EPCs associated with
      underlying disease states has hindered the realization of EPC-based therapy. Here
      we first identify and characterize EPC dysfunction in a rodent model of vascular
      disease (SS/Mcwi rat) that exhibits impaired angiogenesis. To identify molecular
      candidates that mediate the angiogenic potential of these cells, we performed a
      broad analysis of cell surface protein expression using chemical labeling
      combined with mass spectrometry. Analysis revealed EPCs derived from SS/Mcwi rats
      express significantly more type 2 low-affinity immunoglobulin Fc-gamma (FCGR2)
      and natural killer 2B4 (CD244) receptors compared with controls. Genome-wide
      sequencing (RNA-seq) and qt-PCR confirmed isoforms of CD244 and FCGR2a
      transcripts were increased in SS/Mcwi EPCs. EPCs with elevated expression of
      FCGR2a and CD244 receptors are predicted to increase the probability of SS/Mcwi
      EPCs being targeted for death, providing a mechanistic explanation for their
      reduced angiogenic efficacy in vivo. Pathway analysis supported this contention,
      as "key" molecules annotated to cell death paths were differentially expressed in
      the SS/Mcwi EPCs. We speculate that screening and neutralization of cell surface
      proteins that "tag" and impair EPC function may provide an alternative approach
      to utilizing incompetent EPCs in greater numbers, as circulating EPCs are
      depleted in patients with vascular disease. Overall, novel methods to identify
      putative targets for repair of EPCs using discovery-based technologies will
      likely provide a major advance in the field of regenerative medicine. 

PMID- 24022222
TI  - 5'-YRNA fragments derived by processing of transcripts from specific YRNA genes
      and pseudogenes are abundant in human serum and plasma.
AB  - Small noncoding RNAs carry out a variety of functions in eukaryotic cells, and in
      multiple species they can travel between cells, thus serving as signaling
      molecules. In mammals multiple small RNAs have been found to circulate in the
      blood, although in most cases the targets of these RNAs, and even their
      functions, are not well understood. YRNAs are small (84-112 nt) RNAs with poorly
      characterized functions, best known because they make up part of the Ro
      ribonucleoprotein autoantigens in connective tissue diseases. In surveying small
      RNAs present in the serum of healthy adult humans, we have found YRNA fragments
      of lengths 27 nt and 30-33 nt, derived from the 5'-ends of specific YRNAs and
      generated by cleavage within a predicted internal loop. Many of the YRNAs from
      which these fragments are derived were previously annotated only as pseudogenes,
      or predicted informatically. These 5'-YRNA fragments make up a large proportion
      of all small RNAs (including miRNAs) present in human serum. They are also
      present in plasma, are not present in exosomes or microvesicles, and circulate as
      part of a complex with a mass between 100 and 300 kDa. Mouse serum contains far
      fewer 5'-YRNA fragments, possibly reflecting the much greater copy number of YRNA
      genes and pseudogenes in humans. The function of the 5'-YRNA fragments is at
      present unknown, but the processing and secretion of specific YRNAs to produce 5'
      end fragments that circulate in stable complexes are consistent with a signaling
      function. 

PMID- 24022228
TI  - Effect of conversion from ESA with shorter half-life to CERA once monthly for
      maintaining Hb concentration in pre-dialysis CKD patients.
AB  - BACKGROUND: The purpose of this study is to identify whether hemoglobin (Hb)
      concentrations can be maintained, and to investigate changes in biomarkers, when
      switching from erythropoietin stimulating agents (ESA) with shorter half-life to
      once-monthly subcutaneous methoxy polyethylene glycol-epoetin beta (CERA) in pre
      dialysis chronic kidney disease (CKD) patients. METHODS: Pre-dialysis CKD
      patients (n=191) aged >=18 years who maintained their Hb level 10-12 g/dL through
      use of epoetin-alpha, epoetin-beta, or darbepoetin-alpha were enrolled. Hb levels
      and CERA dose was assessed prospectively for 24 weeks. Serum biomarkers related
      to coagulation, endothelial function, and iron metabolism were measured at weeks
      0 and 24. RESULTS: Baseline Hb concentration was 10.8+/-0.6 g/dL Twelve and 24
      weeks after conversion, mean Hb levels were 11.9+/-0.9 and 11.2+/-0.9 g/dL,
      respectively. The mean monthly CERA dose required to maintain Hb levels was
      gradually reduced. Of total 387 dose adjustments, dose increases and decreases
      occurred in 35 (9.0%) and 352 (91.0%) episodes, respectively. Hb overshoot
      occurred in 14 (9.7%) patients. P-selectin was significantly decreased, whereas
      VCAM was significantly increased 24 weeks after conversion (P < 0.05). Serum
      soluble transferrin receptor E-selectin and prohepcidin levels were similar
      before and after switching to CERA (P=N-S). CONCLUSION: Conversion from ESA with
      shorter half-life to subcutaneous once-monthly CERA in pre-dialysis CKD patients
      can efficaciously maintain Hb. The CERA dose requirement decreased significantly.
      The conversion ratio may need to be reduced when switching from ESA with shorter
      half-life to CERA. CERA may change biomarkers associated with platelet reactivity
      and endothelial microenvironment.

PMID- 24022229
TI  - Identification of BACH2 and RAD51B as rheumatoid arthritis susceptibility loci in
      a meta-analysis of genome-wide data.
AB  - OBJECTIVE: A recent high-density fine-mapping (ImmunoChip) study of genetic
      associations in rheumatoid arthritis (RA) identified 14 risk loci with validated
      genome-wide significance, as well as a number of loci showing associations
      suggestive of significance (P = 5 * 10(-5) < 5 * 10(-8)), but these have yet to
      be replicated. The aim of this study was to determine whether these potentially
      significant loci are involved in the pathogenesis of RA, and to explore whether
      any of the loci are associated with a specific RA serotype. METHODS: A total of
      16 single-nucleotide polymorphisms (SNPs) were selected for genotyping and
      association analyses in 2 independent validation cohorts, comprising 6,106 RA
      cases and 4,290 controls. A meta-analysis of the data from the original
      ImmunoChip discovery cohort and from both validation cohorts was carried out, for
      a combined total of 17,581 RA cases and 20,160 controls. In addition, stratified
      analysis of patient subsets, defined according to their anti-cyclic citrullinated
      peptide (anti-CCP) antibody status, was performed. RESULTS: A significant
      association with RA risk (P < 0.05) was replicated for 6 of the SNPs assessed in
      the validation cohorts. All SNPs in the validation study had odds ratios (ORs)
      for RA susceptibility in the same direction as those in the ImmunoChip discovery
      study. One SNP, rs72928038, mapping to an intron of BACH2, achieved genome-wide
      significance in the meta-analysis (P = 1.2 * 10(-8), OR 1.12), and a second SNP,
      rs911263, mapping to an intron of RAD51B, was significantly associated in the
      anti-CCP-positive RA subgroup (P = 4 * 10(-8), OR 0.89), confirming that both are
      RA susceptibility loci. CONCLUSION: This study provides robust evidence for an
      association of RA susceptibility with genes involved in B cell differentiation
      (BACH2) and DNA repair (RAD51B). The finding that the RAD51B gene exhibited
      different associations based on serologic subtype adds to the expanding knowledge
      base in defining subgroups of RA.

PMID- 24022223
TI  - Vascular endothelial growth factor-A signaling in bone marrow-derived endothelial
      progenitor cells exposed to hypoxic stress.
AB  - Bone marrow-derived endothelial progenitor cells (BM-EPCs) are stimulated by
      vascular endothelial growth factor-A (VEGF-A) and other potent proangiogenic
      factors. During angiogenesis, an increase in VEGF-A expression stimulates BM-EPCs
      to enhance endothelial tube formation and contribute to an increase in
      microvessel density. Hypoxia is known to produce an enhanced angiogenic response
      and heightened levels of VEGF-A have been seen in oxygen deprived epithelial and
      endothelial cells, yet the pathways for VEGF-A signaling in BM-EPCs have not been
      described. This study explores the influence of hypoxia on VEGF-A signaling in
      rat BM-EPCs utilizing a novel proteomic strategy to directly identify interacting
      downstream components of the combined VEGF receptor(s) signaling pathways, gene
      expression analysis, and functional phenotyping. VEGF-A signaling network
      analysis following liquid chromatographic separation and tandem mass spectrometry
      revealed proteins related to inositol/calcium signaling, nitric oxide signaling,
      cell survival, cell migration, and inflammatory responses. Alterations in BM-EPC
      expression of common angiogenic genes and tube formation in response to VEGF-A
      during hypoxia were measured and combined with the proteomic analysis to enhance
      and support the signaling pathways detected. BM-EPC tube formation assays in
      response to VEGF-A exhibited little tube formation; however, a cell
      projection/migratory phenotype supported the signaling data. Additionally, a
      novel assay measuring BM-EPC incorporation into preformed endothelial cell tubes
      indicated a significant increase of incorporated BM-EPCs after pretreatment with
      VEGF-A during hypoxia. This study verifies known VEGF-A pathway components and
      reveals several unidentified mechanisms of VEGF-A signaling in BM-EPCs during
      hypoxia that may be important for migration to sites of vascular regeneration. 

PMID- 24022231
TI  - In situ atomic-scale observation of continuous and reversible lattice deformation
      beyond the elastic limit.
AB  - The elastic strain sustainable in crystal lattices is usually limited by the
      onset of inelastic yielding mediated by discrete dislocation activity, displacive
      deformation twinning and stress-induced phase transformations, or fracture
      associated with flaws. Here we report a continuous and gradual lattice
      deformation in bending nickel nanowires to a reversible shear strain as high as
      34.6%, which is approximately four times that of the theoretical elastic strain
      limit for unconstrained loading. The functioning deformation mechanism was
      revealed on the atomic scale by an in situ nanowire bending experiments inside a
      transmission electron microscope. The complete continuous lattice straining
      process of crystals has been witnessed in its entirety for the straining path,
      which starts from the face-centred cubic lattice, transitions through the
      orthogonal path to reach a body-centred tetragonal structure and finally to a re
      oriented face-centred cubic structure. 

PMID- 24022230
TI  - Non-occlusive mesenteric ischemia (NOMI): utility of measuring the diameters of
      the superior mesenteric artery and superior mesenteric vein at multidetector CT.
AB  - OBJECTIVE: To investigate the diagnostic capability of multidetector computed
      tomography for detecting non-occlusive mesenteric ischemia (NOMI). METHODS: We
      studied 11 NOMI patients and 44 controls. Radiologists evaluated the CT images
      for the presence of bowel ischemia and measured the diameters of the superior
      mesenteric artery and the superior mesenteric vein (D SMA and D SMV). We also
      performed linear discriminant analysis (LDA) using D SMA and D SMV. RESULTS: All
      NOMI patients presented with more than 2 CT findings of bowel ischemia. D SMA and
      D SMV were significantly smaller in NOMI patients than in the controls (p <
      0.01). At the optimal cut-off values for D SMA (6.5 mm), D SMV (9.0 mm), and the
      Z value in LDA (0.93), sensitivity and specificity were 81.8 and 81.8; 81.8 and
      88.6; and 81.8 and 97.7 %, respectively. CONCLUSIONS: D SMA and D SMV were
      significantly smaller in NOMI patients than in the controls and D SMV is a more
      significant parameter than D SMA.

PMID- 24022232
TI  - Brain microdialysis and its applications  in experimental neurochemistry.
AB  - Abstract Microdialysis is one of the most powerful neurochemistry techniques,
      which allows the monitoring of changes in the extracellular content of endogenous
      and exogenous substances in the brain of living animals. The strength as well as
      wide applicability of this experimental approach are based on the bulk theory of
      brain neurotransmission. This methodological review introduces basic principles
      of chemical neurotransmission and emphasizes the difference in neurotransmission
      types.Clear understanding of their significance and degree of engagement in
      regulation of physiological processes is an ultimate prerequisite not only for
      choosing an appropriate method of monitoring for interneuronal communication via
      chemical messengers but also for accurate data interpretation. The focus on the
      processes of synthesis/metabolism, receptor interaction/neuronal signaling or the
      behavioral relevance of neurochemical events sculpts the experiment design. Brain
      microdialysis is an important method for examining changes in the content of any
      substances, irrespective of their origin, in living animals. This article
      compares contemporary approaches and techniques that are used for monitoring
      neurotransmission (including in vivo brain microdialysis, voltammetric methods,
      etc). We highlight practical aspects of microdialysis experiments in particular
      to those researchers who are seeking to increase the repertoire of their
      experimental techniques with brain microdialysis.

PMID- 24022233
TI  - Expression of aquaporin water channels in human urothelial carcinoma: correlation
      of AQP3 expression with tumour grade and stage.
AB  - PURPOSE: To study the expression, localization and potential clinical
      significance of aquaporin water channels both in well-established urothelial
      cancer (UC) cell lines and in human bladder carcinoma specimens of different
      stages and grades and to discuss the clinical relevance of the findings. METHODS:
      AQP transcript and protein expression by RT4, RT112 and T24 UC cell lines was
      investigated using reverse transcriptase polymerase chain reaction and
      immunofluorescence labelling. Immunohistochemistry (IHC) was used to assess AQP
      protein expression in 94 UC specimens of various grades and stages. RESULTS: AQP3
      and 9 transcripts were expressed in low-grade RT4 and RT112, but not in high
      grade T24 cells. By contrast, AQP4 mRNA was absent in RT4, but expressed by RT112
      and T24. Transcripts for AQP7 and 11 were detected in all three UC cell lines.
      Immunofluorescence microscopy confirmed the expression of AQP3, 4 and 7 at the
      protein level. By IHC, AQP3 was shown to be intensely expressed by 86 %, 66 % and
      33 % of specimens of stage pTa, pT1 and pT2 tumours, respectively (p < 0.001).
      Whereas 100 % of G1 tumours were positive, only 73 % and 55 % of G2 and G3
      tumours were found to express AQP3 (p = 0.004). CONCLUSIONS: This is the first
      study to demonstrate that several AQPs are expressed in UC. Our results indicate
      that there is a correlation between AQP3 protein expression and tumour stage and
      grade, with AQP3 expression being reduced or lost in tumours of higher grade and
      stage. Taken together with the available evidence from other studies, we conclude
      that AQPs may play a role in the progression of UC and, in particular, that this
      could be of prognostic value.

PMID- 24022234
TI  - Comparison of post-operative intravesical recurrence and oncological outcomes
      after open versus laparoscopic nephroureterectomy for upper urinary tract
      urothelial carcinoma.
AB  - OBJECT: To retrospectively evaluate intravesical recurrence and oncological
      outcomes after open or laparoscopic radical nephroureterectomy (RNU) for the
      upper urinary tract urothelial carcinoma (UUT-UC). PATIENTS AND METHODS: This
      study comprised 122 patients diagnosed UUT-UC and subsequently nephroureterectomy
      was performed on. Several clinical and pathological parameters were emphasized
      for comparison of clinical outcomes. RESULTS: Among 122 patients with UUT-UC, 101
      (82.8 %) and 21 (17.2 %) underwent open or laparoscopic radical
      nephroureterectomy (ONU or LNU), respectively. In univariable and multivariable
      Cox regression models, the surgical procedure exerted an impact neither on post
      operative intravesical recurrence rate (p = 0.179 and 0.213, respectively) nor on
      cancer-specific mortality rate (p = 0.561 and 0.159, respectively). The 1-, 2-
      and 5-year cancer-specific survival (CSS) rates of patients undergoing ONU or LNU
      were 92.1 versus 95.2 %, 87.1 versus 90.5 %, 79.2 versus 85.7 %, respectively,
      and the Kaplan-Meier plot illustrated that patients from two groups enjoyed an
      equivalent survival rate (p = 0.559). Moreover, we added that previous history of
      bladder tumor and pre-operative hydronephrosis was associated with intravesical
      recurrence, whereas three prognostic factors, including pathological tumor stage,
      grade, and lymphovascular invasion, showed possibility to be predictors of cancer
      specific mortality. CONCLUSION: There existed no significant difference of
      intravesical recurrence and CSS between patients after ONU and LNU. Conclusively,
      laparoscopic radical nephroureterectomy did not present superiority to open
      management for patients with UUT-UC.

PMID- 24022235
TI  - Robotic-assisted laparoendoscopic single-site radical nephrectomy: first
      experience with the novel Da Vinci single-site platform.
AB  - PURPOSE: To report our first cases of robotic laparoendoscopic single-site (R
      LESS) radical nephrectomy with the novel Da Vinci R-LESS platform (Intuitive
      Surgical, Sunnyvale, CA). METHODS: Six radical nephrectomies were performed with
      R-LESS Da Vinci single-site port and instruments. Data concerning patients
      characteristics, indication of surgery, operative and postoperative outcomes were
      collected. RESULTS: All procedures were completed successfully. Two patients
      required the placement of an additional port. Median operative, docking and
      console times were 179 min (range 120-318), 19 min (range 15-24) and 129 min
      (range 100-264), respectively. Median blood loss was 100 ml (range 50-800). No
      significant robotic-related problem was noticed during the procedures. There was
      no operative or major postoperative (Clavien >2) complication. Median length of
      hospital stay was 3 days. CONCLUSION: Our initial experience of R-LESS radical
      nephrectomies with the novel Da Vinci platform shows that the procedure is
      feasible. Indications, safety and place of the technique will be confirmed with
      growing experience.

PMID- 24022236
TI  - Neurocognitive effects of ketamine in treatment-resistant major depression:
      association with antidepressant response.
AB  - RATIONALE: The N-methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine
      has demonstrated rapid antidepressant effects in patients with treatment
      resistant depression (TRD). Despite the promise of a novel and urgently needed
      treatment for refractory depression, concerns regarding potential adverse
      neurocognitive effects of ketamine remain. OBJECTIVES: Although extensive
      research has been conducted in healthy volunteers, there is a paucity of studies
      examining the neurocognitive effects of ketamine in depressed patients.
      Therefore, the aims of the current study were to characterize the relationship
      between baseline neurocognition and antidepressant response to ketamine, measure
      the acute impact of ketamine on neurocognition, and investigate the relationship
      between acute neurocognitive effects of ketamine and antidepressant response.
      METHODS: Neurocognitive functioning was assessed in 25 patients with TRD using a
      comprehensive battery: estimated premorbid intelligence quotient (IQ), current
      IQ, and tests from the MATRICS Consensus Cognitive Battery (MCCB). A subset of
      the MCCB was repeated immediately following a 40-min intravenous infusion of
      ketamine (0.5 mg/kg). RESULTS: Patients who responded to ketamine 24 h following
      treatment had poorer baseline neurocognitive performance relative to
      nonresponders and, in particular, slower processing speed (F = 8.42; df = 23; p =
      0.008). Ketamine was associated with selective impairments in memory recall, and
      the degree of cognitive change carried negative prognostic significance (e.g.,
      negative cognitive effects immediately after ketamine predicted lower response
      rate at 24 h; Fisher's exact test two-sided p = 0.027). CONCLUSIONS: Taken
      together, our findings suggest a potential baseline neurocognitive predictor of
      ketamine response and an inverse relationship between the cognitive effects of
      ketamine and antidepressant efficacy.

PMID- 24022237
TI  - The nicotinergic receptor as a target for cognitive enhancement in schizophrenia:
      barking up the wrong tree?
AB  - RATIONALE: Cognitive symptoms have increasingly been recognized as an important
      target in the development of future treatment strategies in schizophrenia. The
      nicotinergic neurotransmission system has been suggested as a potentially
      interesting treatment target for these cognitive deficits. However, previous
      research yielded conflicting results, which may be explained by several
      methodological limitations, such as the failure to include both a group of
      smoking and non-smoking schizophrenic patients, the use of only a single nicotine
      dose, and the inclusion of a very limited cognitive battery. OBJECTIVES: The
      present study aims at investigating the cognitive effects of nicotine in
      schizophrenia while addressing these methodological issues. METHODS: In a double
      blind placebo-controlled randomized crossover design, cognitive effects are
      assessed in smoking (n =16) and non-smoking (n =16) schizophrenic patients after
      receiving active (1 or 2 mg) or placebo oromucosal nicotine spray. RESULTS: A
      modest improving effect of nicotine on attention in the smoking but not the non
      smoking group was found. No enhancing effects were found on measures of visual
      memory, working memory, processing speed, psychomotor speed, or social cognitive
      functioning in either patient group. CONCLUSIONS: These findings suggest that the
      nicotinic receptor only has limited value as a cognitive treatment target in
      schizophrenia.

PMID- 24022238
TI  - Refractoriness to platelet transfusion in acute myeloid leukemia correlated with
      the optical density of anti-platelet factor 4/heparin antibodies.
AB  - A small number of reports have described cases of heparin-induced
      thrombocytopenia complicating hematological disorders with impaired platelet
      production. We describe the case of a 66-year-old woman with acute myeloid
      leukemia who exhibited unexplained refractoriness to platelet transfusion, while
      receiving heparin flushes, and was found to have anti-platelet factor 4
      (PF4)/heparin antibodies with high optical density (OD) values (>2 units)
      detected by an enzyme-linked immunosorbent assay. After cessation of heparin
      flushes, her refractoriness to platelet transfusion resolved. We retrospectively
      confirmed that the OD values for anti-PF4/heparin antibodies declined gradually;
      refractoriness to platelet transfusion resolved when the OD values fell below 1.0
      units. Given the absence of any other evident explanation for this phenomenon,
      and the correlation between the OD values for anti-PF4/heparin antibodies and the
      efficacy of platelet transfusions, we conclude that the patient's refractoriness
      to platelet transfusion was most likely caused by anti-PF4/heparin antibodies
      that had platelet-activating properties.

PMID- 24022239
TI  - Porphyrin adsorbed on the (101[combining macron]0) surface of the wurtzite
      structure of ZnO--conformation induced effects on the electron transfer
      characteristics.
AB  - Electron transfer at the adsorbate-surface interface is crucial in many
      applications but the steps taking place prior to and during the electron transfer
      are not always thoroughly understood. In this work a model system of 4-(porphyrin
      5-yl)benzoic acid adsorbed as a corresponding benzoate on the ZnO wurtzite
      (101[combining macron]0) surface is studied using density functional theory (DFT)
      and time-dependent DFT. Emphasis is on the initial photoexcitation of porphyrin
      and on the strength of coupling between the porphyrin LUMO or LUMO + 1 and the
      ZnO conduction band that plays a role in the electron transfer. Firstly, ZnO
      wurtzite bulk is optimized to minimum energy geometry and the properties of the
      isolated ZnO (101[combining macron]0) surface model and the porphyrin model are
      discussed to gain insight into the combined system. Secondly, various
      orientations of the model porphyrin on the ZnO surface are studied: the porphyrin
      model standing perpendicularly to the surface and gradually brought close to the
      surface by tilting the linker in a few steps. The porphyrin model approaches the
      surface either sideways with hydrogen atoms of the porphyrin ring coming down
      first or twisted in a ca. 45 degrees  angle, giving rise to pi-interactions of
      the porphyrin ring with ZnO. Because porphyrins are closely packed and near the
      surface, emerging van der Waals (vdW) interactions are examined using Grimme's D2
      method. While the orientation affects the initial excitation of porphyrin only
      slightly, the coupling between the LUMO and LUMO + 1 of porphyrin and the
      conduction band of ZnO increases considerably if porphyrin is close to the
      surface, especially if the pi-electrons are interacting with the surface. Based
      on the results of coupling studies, not only the distance between porphyrin and
      the ZnO surface but also the orientation of porphyrin can greatly affect the
      electron transfer. 

PMID- 24022241
TI  - A cross-species socio-emotional behaviour development revealed by a multivariate
      analysis.
AB  - Recent progress in affective neuroscience and social neurobiology has been
      propelled by neuro-imaging technology and epigenetic approach in neurobiology of
      animal behaviour. However, quantitative measurements of socio-emotional
      development remains lacking, though sensory-motor development has been
      extensively studied in terms of digitised imaging analysis. Here, we developed a
      method for socio-emotional behaviour measurement that is based on the video
      recordings under well-defined social context using animal models with variously
      social sensory interaction during development. The behaviour features digitized
      from the video recordings were visualised in a multivariate statistic space using
      principal component analysis. The clustering of the behaviour parameters
      suggested the existence of species- and stage-specific as well as cross-species
      behaviour modules. These modules were used to characterise the behaviour of
      children with or without autism spectrum disorders (ASDs). We found that socio
      emotional behaviour is highly dependent on social context and the cross-species
      behaviour modules may predict neurobiological basis of ASDs. 

PMID- 24022242
TI  - [Single Incision Laparoscopic Cholecystectomy (SILC) - A Novel Technique in
      Comparison with the Gold Standard].
AB  - BACKGROUND: Currently multiport laparoscopic cholecystectomy (LC) represents the
      gold standard for gall bladder removal. However, a single-incision approach might
      succeed it as the future leading technique. To date, final proof for safety and
      applicability remain elusive. METHODS: A retrospective analysis of prospectively
      collected data from 459 patients subjected to multiport (LC) or single incision
      laparoscopic cholecystectomy (SILC) was performed. RESULTS: From 2010 to 2011,
      115 SILC (25 %) and 344 LC (75 %) interventious were performed. Mean follow-up
      was 13.2 (2.1/24.6) months. The SILC group comprised more females (SILC: m : f 1
      : 3.4 vs. LC: 1 : 1.2) and younger patients (SILC: 44.7 vs. LC: 54.9 years) with
      a slightly lower (ASA) score (SILC:1.7 +/- 0.3 vs. LC:1.9 +/- 0.5). SIL
      cholecystectomy was performed more frequently in an elective setting (SILC: 81.7
      vs. LC: 55.5 %). Complication rates were low and did not differ significantly
      between groups (wound infections: SILC: 2.3 vs. LC: 3.19 %; incisional hernias:
      SILC: 0.86 vs. LC: 2.3 %, bile leakage: SILC: 0.86 vs. LC: 0.57 %). SILC was
      associated with shorter operative times (SILC: 70 +/- 31 vs. LC: 80 +/- 27
      minutes; p < 0.001) and reduced postoperative hospital stay (SILC: 3.02 +/- 1.4
      vs. LC: 4.6 +/- 2.8 days; p < 0.001). No conversion to open surgery was required
      with SILC when compared to LC (6 %; 21/334). Within the SILC group, additional
      ports had to be placed in 2.6 % (3/115). CONCLUSION: SILC displays a minimised
      surgical trauma. Compared to LC, SILC showed no disadvantage concerning risk
      profiles, operative times or hospital stay. We believe that SILC can be regarded
      as a natural evolution in the era of minimally invasive surgery.

PMID- 24022240
TI  - Individualized therapy for hepatitis C infection: focus on the interleukin-28B
      polymorphism in directing therapy.
AB  - Hepatitis C virus-a major global cause of chronic hepatitis, cirrhosis, and
      hepatocellular carcinoma-affects millions of people worldwide. Pegylated
      interferon (Peg-IFN) and ribavirin (RBV) had been the standard treatment for a
      decade until availability of the protease inhibitors in 2011. However, current
      antiviral therapy is still IFN-based and is associated with significant side
      effects and variable treatment response. Thus, various host and viral factors
      have been evaluated before and during treatment for the prediction of sustained
      virologic response to antiviral therapy. In 2009, genome-wide association studies
      found the single-nucleotide polymorphisms, located near the host interleukin-28B
      (IL28B) gene that encodes IFN-lambda3, to be the best pretreatment predictor of
      virologic response to Peg-IFN and RBV therapy in chronic hepatitis C genotype 1
      patients. Additionally, inosine triphosphatase (ITPA) gene variants were found to
      be associated with RBV-induced hemolytic anemia, which could affect treatment
      dose for selected patients. IL28B, ITPA, and other treatment predictors allowed
      for a potential individualized approach to treat hepatitis C. In the era of
      increased overall virologic response rates and good tolerability of the rapidly
      developing non-IFN oral direct-acting antiviral therapy regimens, the need for
      individualized treatment is likely to diminish. Various predictors of response,
      including IL28B will likely be of reduced importance in the near future.

PMID- 24022243
TI  - [Vascular Problem Constellations and the Operational Tactical Approaches in Post
      Mortem Liver Transplantations].
AB  - In liver transplantation, vascular problems may occur in the donor as well as in
      the recipient and during the donor operation as well as during the
      transplantation. They have a major influence on the outcome of the
      transplantation. In addition to anatomic variants, arteriosclerotic vascular
      diseases, complications from portal hypertension, vascular lesions from mistakes
      during the donor operation, complications from interventions and bridging
      procedures need to be identified and treated. In addition to duplex sonography
      and contrast enhanced computed tomography, invasive vascular diagnostics (digital
      subtraction angiography) are established for diagnostic purposes. Problem
      constellations should be identified prior to transplantation and the technique of
      the donor operation and the transplantation should be adjusted accordingly.
      Problems that are diagnosed after transplantation may be treated interventionally
      or with open surgery. In a number of cases, vascular complications lead to loss
      of the transplant or death of the recipient from post-operative organ failure.

PMID- 24022244
TI  - [How Much Blood and What Components does the Patient need Intra- and
      Perioperatively?].
AB  - By the optimised availability of less expensive and safe red cell packs and other
      blood products over the last 20 years, numerous surgical interventions have
      become possible without any demand for comments on the precise need. However, a
      number of publications indicates that blood transfusion may also induce
      disadvantageous effects on the postoperative course by immunomodulation, which
      requires a rather restrictive indication for transfusion. Furthermore,
      demographic development leads to a decrease in that portion of the population
      with the potential for blood donation accompanied simultaneously by an increase
      of the percentage of older patients with more need of blood products during
      medical treatment. This makes blood-sparing measures necessary. In addition,
      costs for red cell packs have increased, in particular, for the generally
      compatible blood group 0 - an extra amount for rhesus negative blood. The present
      narrative review highlights, therefore, important news from the clinical
      transfusion medicine, immunohaematology and haemostaseology and their impact on
      daily transfusion practice. In this context, "blood management" is considered as
      one of the very effective blood-sparing measures, which focusses especially i) on
      the substitution of iron in case of depressed preoperative haemoglobin as well as
      ii) to elucidate disorders of coagulation by structured medical history and,
      subsequently, to balance possible need by a specific plan for substitution.
      Simultaneously, prospective studies are initiated to investigate how far the
      transfusion trigger of a patient can be lowered down to a still appropriate
      level. As far as consolidated findings are already available, they are described
      with regard to the single blood components and taking into account the cross
      sectional guidelines of the "Bundesarztekammer" (Federal Physicians Chamber).
      Finally, initial evidence is provided characterising patient- and blood donor
      specific, blood group-dependent features of a reasonable haemotherapy. 

PMID- 24022245
TI  - ["In-situ split" (ISS) liver resection: new aspects of technique and indication].
AB  - The combination of right portal vein ligation with complete parenchyma dissection
      ("in-situ split", ISS) for rapid hypertrophy induction of the left-lateral liver
      lobe is a novel strategy to convert primarily irresectable liver tumours into a
      resectable stage. Available data so far show a 60-80 % growth induction of the
      remnant liver within 7(- 9) days. Certainly, a novel concept that comprises two
      operations within a very short time period raises questions. Based on the very
      few literature reports that have been published so far, as well as our own
      experience, we here discuss technical issues such as the use of a plastic sheet
      on the resection margin, the possibility of laparoscopic dissection and the
      timing of the second operation. Moreover, aspects of the preoperative diagnostic
      work-up that is necessary are assessed. Finally, open questions, e.g., concerning
      the influence of preoperative chemotherapy and the use of ISS in patients with
      cirrhosis are evaluated. In summary, the assessment of chances and risks of this
      novel concept with regard to indication and technical issues helps to provide the
      potentially curative option of the "in-situ split" procedure to more patients
      with marginal or even irresectable liver tumours. 

PMID- 24022247
TI  - A bis-phenolate for the construction of linear lanthanide trimers.
AB  - The ligand bis(5-tert-butyl-2-hydroxy-3-hydroxymethyl-phenyl)methane, a flexible
      calix[n]arene analogue, is employed to construct an unusual linear [Ln3] trimer. 

PMID- 24022248
TI  - Caregiver burden in frontotemporal degeneration and corticobasal syndrome.
AB  - BACKGROUND AND AIMS: Caregiver stress is often a serious problem when caring for
      a patient with frontal lobe dysfunction. METHODS: A total of 102 caregivers of
      both patients with frontotemporal degeneration and corticobasal syndrome
      completed the Frontal Systems Behavior Scale (FrSBe) and the Zarit Burden
      Interview (ZBI). To analyze the association between apathy or disinhibition (or
      both) and caregiver burden, the effects of the total FrSBe and the apathy and
      disinhibition subscales of the FrSBE on the total ZBI score were assessed with
      logistic regressions and t tests. RESULTS: Total FrSBE score and the apathy FrSBE
      subscore predicted caregiver burden. Apathy occurred without disinhibition, and
      the two occurred together, but disinhibition without apathy was very rare.
      CONCLUSIONS: Disinhibition without apathy occurred very rarely. Apathy was more
      associated with caregiver burden than disinhibition.

PMID- 24022250
TI  - exo-Selective construction of spiro-[butyrolactone-pyrrolidine] via 1,3-dipolar
      cycloaddition of azomethine ylides with alpha-methylene-gamma-butyrolactone
      catalyzed by Cu(I)/DTBM-BIPHEP.
AB  - An expedient access to optically active spiro-[butyrolactone-pyrrolidine] was
      successfully developed via an unprecedented Cu(I)-catalyzed exo-selective 1,3-DC
      of azomethine ylides with alpha-methylene-gamma-butyrolactone, which exhibited
      high diastereoselectivity (>98 : 2), excellent enantioselectivity (96->99% ee)
      and a broad substrate scope under mild conditions.

PMID- 24022249
TI  - Impact of patellar height on unicompartment knee arthroplasty: does patella baja
      lead to an inferior outcome?
AB  - BACKGROUND: Though a number of series with long-term results have been published,
      there is still a paucity of literature on the role of patellar height after
      unicompartment knee arthroplasty (UKA). The present study was conducted with a
      hypothesis that patella baja may lead to a poor outcome at follow-up. MATERIALS
      AND METHODS: A retrospective review of 134 knees was performed and patellar
      height calculated before and after UKA by Blackburne-Peel index (BPI) and the
      Insall-Salvati ratio (ISR) on true lateral radiographs of the patients in 30
      degrees  of flexion taken pre-operatively and at 1 year, 2 years and final follow
      up (minimum 5 years). Statistical analysis was performed to evaluate the
      outcomes. RESULTS: There was a decrease in ISR in 14.18 % and in BPI in 19.4 % at
      final follow-up. There was a significant decrease in BPI values while the
      decrease was not significant for ISR. After eliminating the pre-operative patella
      baja, 7.3 % developed post-operative patella baja, according to ISR, while 11.5 %
      developed patella baja as per BPI. At final follow-up there was a statistically
      significant decrease in stair climbing scores in patients with patella baja when
      compared to patients with normal ISR. CONCLUSION: Patients with a decrease in
      patellar height as per ISR have a decrease in stair climbing score at mid-term
      follow-up while the overall KSS, and pain scores are not affected by a change in
      patellar height and neither is there a significant progress in patellofemoral
      osteoarthritis among patients with patella baja compared to normal patella.

PMID- 24022251
TI  - YUCCA8 and YUCCA9 overexpression reveals a link between auxin signaling and
      lignification through the induction of ethylene biosynthesis.
AB  - Auxin is associated with the regulation of virtually every aspect of plant growth
      and development. Many previous genetic and biochemical studies revealed that,
      among the proposed routes for the production of auxin, the so-called indole-3
      pyruvic acid (IPA) pathway is the main source for indole-3-acetic acid (IAA) in
      plants. The IPA pathway involves the action of 2 classes of enzymes, tryptophan
      pyruvate aminotransferases (TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS
      1(TAA1)/TRYPTOPHAN AMINOTRANSFERASE RELATED (TAR)) and flavin monooxygenases
      (YUCCA). Both enzyme classes appear to be encoded by small gene families in
      Arabidopsis consisting of 5 and 11 members, respectively. We recently showed that
      it is possible to induce transcript accumulation of 2 YUCCA genes, YUC8 and YUC9,
      by methyl jasmonate treatment. Both gene products were demonstrated to contribute
      to auxin biosynthesis in planta. (1) Here we report that the overexpression of
      YUC8 as well as YUC9 led to strong lignification of plant aerial tissues.
      Furthermore, new evidence indicates that this abnormally strong secondary growth
      is linked to increased levels of ethylene production. 

PMID- 24022252
TI  - The evaluation of prevalence of fibromyalgia in patients with chronic urticaria.
AB  - BACKGROUND: The pathophysiology of chronic idiopathic urticaria (CIU) is not
      fully understood; however, it has been hypothesized that a subset of people with
      CIU may have an autoimmune disease and that peripheral cutaneous nerve fibers may
      be involved in CIU. Similarly, it has been postulated that fibromyalgia syndrome
      (FMS) is an autoimmune disorder and may be associated with alterations of
      peripheral cutaneous nerve fibers. Accordingly, the present study aimed to
      determine whether the frequency of FMS is higher in patients with CIU.
      MATERIAL/METHODS: A total of 72 patients with CIU and 67 sex- and age-matched
      healthy controls were included. Urticaria activity score (UAS), fibromyalgia
      impact questionnaire (FIQ), tender point number, and visual analogue scale (VAS)
      were assessed. RESULTS: The frequency of FMS was similar between the groups (9.7%
      vs. 4.5%, p=0.32). However, symptom duration of FMS was significantly longer, and
      tender point number and FIQ were significantly higher in patients with CIU than
      in controls. In addition, patients with CIU had significantly higher VAS scores.
      UAS was significantly correlated with presence of FMS, symptom duration of FMS,
      tender point number, and FIQ and VAS scores. Logistic regression analysis
      revealed that UAS was an independent predictor of presence of FMS (b=0.34,
      p=0.003). CONCLUSIONS: Frequency of FMS was slightly, but not significantly,
      higher in patients with CIU than in controls. However, symptom duration of FMS,
      tender point number, and FIQ and VAS scores were significantly higher in patients
      with CIU, and UAS reflecting severity of the disease was significantly and
      independently associated with presence of FMS.

PMID- 24022253
TI  - Confusion secondary to herpes simplex infection.

PMID- 24022254
TI  - Diwali in the HIV Ward.

PMID- 24022255
TI  - The next step in opening access to care.

PMID- 24022256
TI  - Extensor mechanism disruptions.

PMID- 24022258
TI  - AIE cation functionalized layered zirconium phosphate nanoplatelets: ion-exchange
      intercalation and cell imaging.
AB  - An aggregation-induced emission (AIE) probe, possessing a quaternary
      tetraphenylethene (TPEN) cation, was successfully intercalated into layered alpha
      zirconium phosphate (alpha-ZrP) nanosheets by ion-exchange. The hybrid materials
      emit strong blue emissions in aqueous solution which can be used as an effective
      fluorescence label for HeLa cells. 

PMID- 24022257
TI  - Litter quality versus soil microbial community controls over decomposition: a
      quantitative analysis.
AB  - The possible effects of soil microbial community structure on organic matter
      decomposition rates have been widely acknowledged, but are poorly understood.
      Understanding these relationships is complicated by the fact that microbial
      community structure and function are likely to both affect and be affected by
      organic matter quality and chemistry, thus it is difficult to draw mechanistic
      conclusions from field studies. We conducted a reciprocal soil inoculum * litter
      transplant laboratory incubation experiment using samples collected from a set of
      sites that have similar climate and plant species composition but vary
      significantly in bacterial community structure and litter quality. The results
      showed that litter quality explained the majority of variation in decomposition
      rates under controlled laboratory conditions: over the course of the 162-day
      incubation, litter quality explained nearly two-thirds (64%) of variation in
      decomposition rates, and a smaller proportion (25%) was explained by variation in
      the inoculum type. In addition, the relative importance of inoculum type on soil
      respiration increased over the course of the experiment, and was significantly
      higher in microcosms with lower litter quality relative to those with higher
      quality litter. We also used molecular phylogenetics to examine the relationships
      between bacterial community composition and soil respiration in samples through
      time. Pyrosequencing revealed that bacterial community composition explained 32 %
      of the variation in respiration rates. However, equal portions (i.e., 16%) of the
      variation in bacterial community composition were explained by inoculum type and
      litter quality, reflecting the importance of both the meta-community and the
      environment in bacterial assembly. Taken together, these results indicate that
      the effects of changing microbial community composition on decomposition are
      likely to be smaller than the potential effects of climate change and/or litter
      quality changes in response to increasing atmospheric CO2 concentrations or
      atmospheric nutrient deposition.

PMID- 24022259
TI  - Soft tissue preservation in a fossil marine lizard with a bilobed tail fin.
AB  - Mosasaurs are secondarily aquatic squamates that became the dominant marine
      reptiles in the Late Cretaceous about 98-66 million years ago. Although early
      members of the group possessed body shapes similar to extant monitor lizards,
      derived forms have traditionally been portrayed as long, sleek animals with
      broadened, yet ultimately tapering tails. Here we report an extraordinary
      mosasaur fossil from the Maastrichtian of Harrana in central Jordan, which
      preserves soft tissues, including high fidelity outlines of a caudal fluke and
      flippers. This specimen provides the first indisputable evidence that derived
      mosasaurs were propelled by hypocercal tail fins, a hypothesis that was
      previously based on comparative skeletal anatomy alone. Ecomorphological
      comparisons suggest that derived mosasaurs were similar to pelagic sharks in
      terms of swimming performance, a finding that significantly expands our
      understanding of the level of aquatic adaptation achieved by these seagoing
      lizards. 

PMID- 24022260
TI  - Comparison of dual-energy X-ray absorptiometry, air displacement plethysmography
      and bioelectrical impedance analysis for the assessment of body composition in
      morbidly obese women.
AB  - BACKGROUND/OBJECTIVES: We evaluated the agreement of air displacement
      plethysmography (ADP) and bioelectrical impedance analysis (BIA) with dual-energy
      X-ray absorptiometry (DXA) for the assessment of percent fat mass (%FM) in
      morbidly obese women. SUBJECTS/METHODS: Fifty-seven women aged 19-55 years and
      with a body mass index (BMI) ranging from 37.3 to 55.2 kg/m(2) were studied.
      Values of %FM were obtained directly from ADP and DXA, whereas for BIA we
      estimated fat-free mass (FFM) from an equation for morbidly obese subjects and
      calculated %FM as (weight-FFM)/weight. RESULTS: The mean (s.d.) difference
      between ADP and DXA for the assessment of %FM was -2.4% (3.3%) with limits of
      agreement (LOA) from -8.8% to 4.1%. The mean (s.d.) difference between BIA and
      DXA for the assessment of %FM was 1.7% (3.3%) with LOA from -4.9% to 8.2%.
      CONCLUSION: ADP-DXA and BIA-DXA are not interchangeable methods for the
      assessment of body composition in morbidly obese women.

PMID- 24022261
TI  - The effect of a school-based iron intervention on the haemoglobin concentration
      of school children in north-west Pakistan.
AB  - BACKGROUND/OBJECTIVE: To assess the effectiveness of iron supplements
      administered to school children through a longitudinal school health intervention
      in terms of child haemoglobin concentration and anaemia prevalence.
      SUBJECTS/METHODS: Children and adolescents aged 5-17 years were selected from 30
      schools in north-west Pakistan for a longitudinal iron supplement intervention.
      Children received once-weekly iron supplements (200 mg ferrous sulphate
      containing 63 mg of elemental iron) for 24 weeks (n=352); or the same supplements
      twice-weekly for 12 weeks (n=298) or received no tablets (n=298). Haemoglobin
      concentration was estimated in finger-prick blood samples at baseline, 12 and 24
      weeks. Follow-up samples were taken at 36 weeks. RESULTS: A non-significant
      increase in haemoglobin concentration was observed in children receiving iron
      supplements after 12 weeks (mean 1.4 g/l s.d. 15.0 g/l in once-weekly versus 2.5
      g/l s.d. 14.5 g/l in twice-weekly) compared with the group receiving no iron
      supplements. There was no significant reduction in the prevalence of anaemia in
      the once-weekly or twice-weekly group compared with the unsupplemented group. The
      prevalence of anaemia increased in all three groups during the follow-up period
      (24-36 weeks). CONCLUSIONS: Once-weekly and twice-weekly iron supplements were
      not associated with significant increases in haemoglobin concentration compared
      with unsupplemented children. In all groups, baseline haemoglobin concentration
      was the strongest predictor of haemoglobin increase. The lack of improvement may
      stem from the moderate baseline prevalence of anaemia (33%); other micronutrient
      deficiencies; variable compliance; or the worsening of haemoglobin status owing
      to seasonal changes in dietary iron and other nutrients.

PMID- 24022263
TI  - Time resolved dynamics of phonons and rotons in solid parahydrogen.
AB  - We use femtosecond optical Kerr effect (OKE) spectroscopy to perform time- and
      wavelength-resolved pump-probe measurements on the energetics and lifetimes of
      transverse optical phonons and J = 2 rotons in solid para-hydrogen (pH2). By
      systematically studying the OKE spectroscopy of pH2 in the gas, liquid, and solid
      phases for delay times up to 300 ps, we can disentangle homodyne and heterodyne
      contributions in the solid to the signal that results from the slow phonon (900
      fs) and fast roton (94 fs) dynamics. In solid pH2 at 8.5 K, the energies of the J
      = 2 Raman-active rotons are measured to be 351.98(8) cm(-1), 353.99(8) cm(-1),
      and 356.00(8) cm(-1) corresponding to the crystal field split MJ = +/-1, +/-2,
      and 0 substates. Consistent with the picture of quasi-free molecular rotation
      within the solid, we observe long-lived roton coherences with T2 lifetimes of
      132(5), 114(5), and 82(5) ps for the MJ = +/-1, +/-2, and 0 substates. In
      contrast, similar measurements on normal-hydrogen (nH2) solids which nominally
      contain 75% ortho-hydrogen (oH2) and 25% pH2 molecules display qualitatively
      different roton dynamics; no persistent roton excitations are observed but rather
      overdamped librational excitations that decay within 3 ps. The measured low
      temperature T2 dephasing time of gaseous pH2 implies a collision cross section of
      2.08(10) A(2) which is close to the theoretical value for so-called elastic
      resonant collisions whereby rotational energy is exchanged between the two
      colliding partners, but the sum of the rotational energies is preserved. We argue
      that this same collisional process also determines the T2 dephasing lifetimes in
      the liquid and solid phases. Finally, OKE spectroscopy on pH2 solids with oH2
      concentrations of 1-3% shows evidence for extremely long-lived rotational
      coherences which likely correspond to J = 2 rotons that are pinned next to single
      oH2 impurities within the pH2 solid. 

PMID- 24022262
TI  - Comparability of methods assigning monetary costs to diets: derivation from
      household till receipts versus cost database estimation using 4-day food diaries.
AB  - BACKGROUND/OBJECTIVES: Diet cost could influence dietary patterns, with potential
      health consequences. Assigning a monetary cost to diet is challenging, and there
      are contrasting methods in the literature. This study compares two methods-a food
      cost database linked to 4-day diet diaries and an individual cost calculated from
      household till receipts. SUBJECTS/METHODS: The Diet and Nutrition Tool for
      Evaluation (DANTE) had supermarket prices (cost per 100 g) added to its food
      composition table. Agreement between diet costs calculated using DANTE from food
      diaries and expenditure recorded using food purchase till receipts for 325
      individuals was assessed using correlation and Bland Altman (BA) plots. RESULTS:
      The mean difference between the methods' estimates was L0.10. The BA showed 95%
      limits of agreement of L2.88 and -L3.08. Excluding the highest 5% of diet cost
      values from each collection method reduced the mean difference to L0.02, with
      limits of agreement ranging from L2.31 to -L2.35. Agreement between the methods
      was stronger for males and for adults. CONCLUSIONS: Diet cost estimates using a
      food price database with 4-day food diaries are comparable to recorded
      expenditure from household till receipts at the population or group level. At the
      individual level, however, estimates differed by as much as L3.00 per day. The
      methods agreed less when estimating diet costs of children, females or those with
      more expensive diets.

PMID- 24022264
TI  - Structural disorder and anomalous diffusion in random packing of spheres.
AB  - Nowadays Nuclear Magnetic Resonance diffusion (dNMR) measurements of water
      molecules in heterogeneous systems have broad applications in material science,
      biophysics and medicine. Up to now, microstructural rearrangement in media has
      been experimentally investigated by studying the diffusion coefficient (D(t))
      behavior in the tortuosity limit. However, this method is not able to describe
      structural disorder and transitions in complex systems. Here we show that,
      according to the continuous time random walk framework, the dNMR measurable
      parameter alpha, quantifying the anomalous regime of D(t), provides a
      quantitative characterization of structural disorder and structural transition in
      heterogeneous systems. To demonstrate this, we compare alpha measurements
      obtained in random packed monodisperse micro-spheres with Molecular Dynamics
      simulations of disordered porous media and 3D Monte Carlo simulation of particles
      diffusion in these kind of systems. Experimental results agree well with
      simulations that correlate the most used parameters and functions characterizing
      the disorder in porous media. 

PMID- 24022265
TI  - Renal and extrarenal effects of gum arabic ( Acacia senegal )--what can be
      learned from animal experiments?
AB  - Gum arabic (GA), a water-soluble dietary fiber rich in Ca(2+), Mg(2+) and K(+),
      is used in Middle Eastern countries for the treatment of patients with chronic
      kidney disease. Recent animal experiments shed some light into mechanisms
      involved in the therapeutic action of GA. According to experiments in healthy
      mice, GA treatment increases creatinine clearance, enhances renal excretion of
      ADH, Mg(2+) and Ca(2+), decreases plasma phosphate concentration as well as
      urinary excretion of phosphate and Na(+). In diabetic mice GA treatment increases
      urinary Ca(2+) excretion, and decreases plasma phosphate concentration, plasma
      urea concentration, urinary flow rate, natriuresis, phosphaturia, glucosuria,
      proteinuria as well as blood pressure. Extrarenal effects of GA treatment in mice
      include decreased expression of intestinal Na(+) coupled glucose carrier SGLT1
      with subsequent delay of electrogenic intestinal glucose transport, glucose
      induced hyperglycemia, hyperinsulinemia and body weight gain. GA treatment
      decreases colonic transcription of the angiogenetic factors angiogenin 1,
      angiogenin 3 and angiogenin 4, of CD38 antigen, aquaporin4, interleukin18, vav-3
      oncogene, y(+)-amino acid-transporter, sulfatase1, ubiquitinD and chemokine
      ligand5. Moreover, GA treatment decreases angiogenin and beta-catenin protein
      expression. Accordingly, GA treatment counteracts the development of tumors
      following chemical cancerogenesis. In mouse dendritic cells, antigen-presenting
      cells linking innate and adaptive immunity, GA treatment modifies maturation and
      cytokine release. GA treatment further favourably influences the course of murine
      malaria. The effects of GA treatment on plasma phosphate concentration, blood
      pressure and proteinuria may prove beneficial in chronic renal failure and
      diabetic nephropathy. The effect of GA on intestinal glucose transport may be
      useful in the prophylaxis and treatment of obesity and diabetes, the effect of GA
      on angiogenin and beta-catenin expression could be exploited for the prophylaxis
      against colon carcinoma, the effects of GA on angiogenin expression and dendritic
      cells may be useful in the treatment of inflammatory disease and malaria.

PMID- 24022266
TI  - Oceanobacillus-like bacterium isolated from Vyhna travertine spring.
AB  - During characterization of autochthonic Vyhna travertine source microflora,
      several bacterial strains were isolated and characterised. Isolate T6, a
      halotolerant, moderately alkaliphilic and thermophilic bacterial isolate, was
      further characterised based on physiological, microbiological and biochemical
      tests and phylogenetic 16S rRNA analysis. On the basis of the results obtained,
      the T6 isolate should be placed in the genus Oceanobacillus, and it is probably a
      prototype of a novel bacterial species. Characterization of the T6 isolate
      broadens our knowledge on variability of halophilic bacteria of Oceanobacillus
      genus and expands data on travertine-associated bacterial communities. 

PMID- 24022268
TI  - A native electrophoretic technique to study oligomerization and activity of
      cytosolic 5'-nucleotidase II.
AB  - The analysis of the oligomeric active state of a native protein usually requires
      the application of at least two analytical methods such as gel filtration and
      analytical ultracentrifugation. Both methods require a substantial amount of
      protein, time and/or expensive equipment. We here describe a native
      electrophoretic method for the identification of the native molecular weight of
      the recombinant wild-type cytosolic 5'-nucleotidase (cN-II) and of its mutants in
      subunit interfaces Y115A, F36R, K311A and G319Q. The protein was stained both
      with protein dye and with an activity staining method. Our results demonstrated
      that purified recombinant protein preparations contained substantial amounts of
      nucleic acids and misfolded, inactive protein. Furthermore, cN-II mutants K311A
      and G319Q in subunit interface assume a quaternary dimeric active form, while the
      only active quaternary structure of wild-type cN-II is the tetramer.

PMID- 24022267
TI  - Disarming the jasmonate-dependent plant defense makes nonhost Arabidopsis plants
      accessible to the American serpentine leafminer.
AB  - Here, we analyzed the interaction between Arabidopsis (Arabidopsis thaliana) and
      the American serpentine leafminer (Liriomyza trifolii), an important and
      intractable herbivore of many cultivated plants. We examined the role of the
      immunity-related plant hormone jasmonate (JA) in the plant response and
      resistance to leafminer feeding to determine whether JA affects host suitability
      for leafminers. The expression of marker genes for the JA-dependent plant defense
      was induced by leafminer feeding on Arabidopsis wild-type plants. Analyses of JA
      insensitive coi1-1 mutants suggested the importance of JA in the plant response
      to leafminer feeding. The JA content of wild-type plants significantly increased
      after leafminer feeding. Moreover, coi1-1 mutants showed lower feeding resistance
      against leafminer attack than did wild-type plants. The number of feeding scars
      caused by inoculated adult leafminers in JA-insensitive coi1-1 mutants was higher
      than that in wild-type plants. In addition, adults of the following generation
      appeared only from coi1-1 mutants and not from wild-type plants, suggesting that
      the loss of the JA-dependent plant defense converted nonhost plants to accessible
      host plants. Interestingly, the glucosinolate-myrosinase defense system may play
      at most a minor role in this conversion, indicating that this major antiherbivore
      defense of Brassica species plants probably does not have a major function in
      plant resistance to leafminer. Application of JA to wild-type plants before
      leafminer feeding enhanced feeding resistance in Chinese cabbage (Brassica rapa),
      tomato (Solanum lycopersicum), and garland chrysanthemum (Chrysanthemum
      coronarium). Our results indicate that JA plays an important role in the plant
      response and resistance to leafminers and, in so doing, affects host plant
      suitability for leafminers. 

PMID- 24022269
TI  - The organ crisis: a disaster of our own making.

PMID- 24022270
TI  - Disease-activity-free status in patients with relapsing-remitting multiple
      sclerosis treated with daclizumab high-yield process in the SELECT study.
AB  - BACKGROUND: Daclizumab high-yield process (DAC HYP) is a humanized anti-CD25
      monoclonal antibody that inhibits high-affinity interleukin-2 receptor signaling.
      OBJECTIVE: The objective of this paper is to assess the proportion of DAC HYP-
      versus placebo-treated patients who were free from disease activity. METHODS:
      SELECT was a randomized, double-blind, multicenter study of DAC HYP 150 mg or 300
      mg, or placebo, administered subcutaneously every four weeks for 52 weeks. In
      this post-hoc analysis of the SELECT trial, 'disease-activity free' was defined
      as completion through week 52 without relapses or confirmed three-month
      disability progression (clinical), with no new/newly enlarging T2-hyperintense
      lesions and no new gadolinium-enhancing lesions at the week 52 scan
      (radiological). Primary analyses were based on logistic regression controlling
      for baseline characteristics. RESULTS: More DAC HYP-treated (39%, n = 156) versus
      placebo-treated patients (11%, n = 22) were disease-activity free (odds ratio
      (95% confidence interval), 6.18 (3.71-10.32); p < 0.0001). Furthermore, 77% and
      48% of DAC HYP-treated patients were free from clinical or radiological disease
      activity, respectively, compared with 60% and 18% of placebo-treated patients.
      CONCLUSION: At one year, DAC HYP resulted in a meaningful increase in the
      proportion of relapsing-remitting MS patients who were disease-activity free
      versus placebo.

PMID- 24022271
TI  - Neuropsychological rehabilitation should not aim only at better cognitive task
      scores: a reply to the letter of Cerasa, Tomaiuolo and Quattrone.

PMID- 24022272
TI  - In silico selection of Arabidopsis thaliana ecotypes with enhanced stress
      tolerance.
AB  - Climate models predict increased occurrences of combined abiotic and biotic
      stress. Unfortunately, most studies on plant stress responses include single or
      double stress scenarios only. Recently, we established a multi-factorial system
      in Arabidopsis thaliana (Arabidopsis) to study the influence of simultaneously
      applied heat, drought, and virus. Our transcriptome analysis revealed that gene
      expression under multi-factorial stress is not predictable from single stress
      treatments. Combined heat and drought stress reduced expression of defense genes
      and genes involved in R-mediated disease responses, which correlated with
      increased susceptibility of Arabidopsis to virus infection. Eleven genes were
      found to be differentially regulated under all stress conditions. Assuming that
      regulated expression of these genes is important for plant fitness, Arabidopsis
      ecotypes were clustered according to their expression. Interestingly, ecotypes
      showing a close correlation to stressed Col-0 prior stress treatment showed
      improved growth under stress conditions. This result suggests a functional
      relevance of these genes in stress tolerance. 

PMID- 24022273
TI  - Psychological and behavioural factors associated with long-term weight
      maintenance after a multidisciplinary treatment of uncomplicated obesity.
AB  - Obesity is a multifactorial syndrome and the likelihood of success of a medical
      nutritional treatment (MNT) over the long term is low. As psychological and
      behavioural factors have an important role in both pathogenesis and the treatment
      of obesity, these issues were investigated in individuals with obesity who
      reported a long-term success or a failure in terms of weight loss following a
      MNT. Eighty-eight individuals of an original cohort of 251 subjects were re
      evaluated 10 years after a MNT with cognitive-behavioural approach for
      uncomplicated obesity. Fifty-three participants were classified as failure (body
      weight change >=0.5 kg) and 35 as a success (10-year body weight change <0.5 kg)
      of the MNT. Prior to the beginning of the weight-management program, both the
      Dieting Readiness Test (DRT) and the Hospital Anxiety and Depression Scale (HADS)
      were administered. At a 10-year follow-up after the MNT, self-reported
      questionnaires were administered: quality of life was assessed by the Obesity
      Related Well-Being (ORWELL 97) questionnaire, eating attitudes and behaviours by
      the Eating Disorder Examination Questionnaire (EDE-Q), the Binge Eating Scale
      (BES) investigated the presence and severity of binge eating and the Symptom
      Checklist (SCL 90-R) was used to identify the psychopathological distress. The
      scores of the ORWELL 97 items concerning symptoms (P = 0.005), discomfort (P =
      0.03) and the total score (P = 0.02) were significantly lower in the success
      group. The depression score of the HADS was positively correlated with the
      percentage of body weight change observed 10 years after the MNT (r = 0.22; P =
      0.045). The scores of the shape concern (EDE-Q) (r = 0.35; P = 0.013) and of the
      discomfort (ORWELL 97) (r = 0.36; P = 0.012) were significantly correlated with
      the percentage of body weight change 10 years after the MNT. In conclusion, this
      study is in agreement with the possibility that the psychological quality of life
      is associated even with modest amounts of weight loss in the long run. Further
      research should support identifying successful predictors of weight loss.

PMID- 24022274
TI  - Salicylic acid alleviates adverse effects of heat stress on photosynthesis
      through changes in proline production and ethylene formation.
AB  - We investigated the potential of salicylic acid (SA) in alleviating the adverse
      effects of heat stress on photosynthesis in wheat (Triticum aestivum L.) cv WH
      711. Activity of ribulose 1,5-bisphosphate carboxylase (Rubisco), photosynthetic
      nitrogen use efficiency (NUE), and net photosynthesis decreased in plants
      subjected to heat stress (40  degrees C for 6 h), but proline metabolism
      increased. SA treatment (0.5 mM) alleviated heat stress by increasing proline
      production through the increase in gamma-glutamyl kinase (GK) and decrease in
      proline oxidase (PROX) activity, resulting in promotion of osmotic potential and
      water potential necessary for maintaining photosynthetic activity. Together with
      this, SA treatment restricted the ethylene formation in heat-stressed plants to
      optimal range by inhibiting activity of 1-aminocyclopropane carboxylic acid (ACC)
      synthase (ACS). This resulted in improved proline metabolism, N assimilation and
      photosynthesis. The results suggest that SA interacts with proline metabolism and
      ethylene formation to alleviate the adverse effects of heat stress on
      photosynthesis in wheat.

PMID- 24022275
TI  - Aberrant muscle antigen exposure in mice is sufficient to cause myositis in a
      Treg cell-deficient milieu.
AB  - OBJECTIVE: Myositis is associated with muscle-targeted inflammation and is
      observed in some Treg cell-deficient mouse models. Because an autoimmune
      pathogenesis has been strongly implicated, the aim of this study was to
      investigate the hypothesis that abnormal exposure to muscle antigens, as observed
      in muscle injury, can induce autoimmune-mediated myositis in susceptible hosts.
      METHODS: FoxP3 mutant (scurfy) mice were mated to synaptotagmin VII (Syt VII)
      mutant mice, which resulted in a new mouse strain that combines impaired membrane
      resealing with Treg cell deficiency. Lymphocyte preparations from double-mutant
      mice were adoptively transferred intraperitoneally, with or without purified Treg
      cells, into recombination-activating gene 1 (RAG-1)-null recipients. Lymph node
      cells from mice with the FoxP3 mutation were transferred into RAG-1-null mice
      either 1) intraperitoneally in conjunction with muscle homogenate or purified
      myosin protein or 2) intramuscularly with or without cotransfer of purified Treg
      cells. RESULTS: FoxP3-deficient mouse lymph node cells transferred in conjunction
      with myosin protein or muscle homogenate induced robust skeletal muscle
      inflammation. The infiltrates consisted predominantly of CD4+ and CD8+ T cells, a
      limited number of macrophages, and no B cells. Significant inflammation was also
      seen in similar experiments using lymph node cells from FoxP3/Syt VII double
      mutant mice but was absent in experiments using adoptive transfer of FoxP3 mutant
      mouse cells alone. The cotransfer of Treg cells completely suppressed myositis.
      CONCLUSION: These data, derived from a new, reproducible model, demonstrate the
      critical roles of Treg cell deficiency and aberrant muscle antigen exposure in
      the priming of autoreactive cells to induce myositis. This mouse system has
      multifaceted potential for examining the interplay in vivo between tissue injury
      and autoimmunity.

PMID- 24022276
TI  - Multiple interactions of NaHER1 protein with abscisic acid signaling in Nicotiana
      attenuata plants.
AB  - Previously, we identified a novel herbivore elicitor-regulated protein in
      Nicotiana attenuata (NaHER1) that is required to suppress abscisic acid (ABA)
      catabolism during herbivore attack and activate a full defense response against
      herbivores. ABA, in addition to its newly defined role in defense activation,
      mainly controls seed germination and stomatal function of land plants. Here we
      show that N. attenuata seeds silenced in the expression of NaHER1 by RNA
      interference (irHER1) accumulated less ABA during germination, and germinated
      faster on ABA-containing media compared to WT. Curiously, epidermal cells of
      irHER1 plants were wrinkled, possibly due to the previously demonstrated increase
      in transpiration of irHER1 plants that may affect turgor and cause wrinkling of
      the cells. We conclude that NaHER1 is a highly pleiotropic regulator of ABA
      responses in N. attenuata plants. 

PMID- 24022277
TI  - Association between EEG abnormalities and CSF biomarkers in a memory clinic
      cohort.
AB  - BACKGROUND: The aim of the study was to describe distinct electroencephalogram
      (EEG) phenotypes defined after routine visual EEG analysis in a large memory
      clinic cohort and to investigate their relationship to cerebrospinal fluid (CSF)
      biomarkers. METHODS: Patients with Alzheimer's disease (n = 131), mild cognitive
      impairment (n = 285), subjective cognitive impairment (n = 310), and mixed
      dementia (n = 29) were assessed clinically with neuroimaging, EEG and CSF
      investigations. EEG phenotypes were based on frequency of background activity
      (BA) and presence and degree of episodic abnormalities (EA). RESULTS: BA and EA
      differed significantly (p < 0.001) between diagnostic groups. A lower CSF amyloid
      beta42/phospho-tau ratio and higher total tau were associated with slower BA (p <
      0.01) and a higher degree of EA (p < 0.04). CONCLUSIONS: Slowing of BA in
      combination with EA seems to be related to biological markers of
      neurodegeneration.

PMID- 24022278
TI  - Detection of MYCN amplification using blood plasma: noninvasive therapy
      evaluation and prediction of prognosis in neuroblastoma.
AB  - PURPOSE: Amplification of neuroblastoma derived (avian)v-myc myelocytomatosis
      viral related oncogene (MYCN) is an important risk-stratified indicator in
      neuroblastoma. To evaluate the feasibility of noninvasive measurement of MYCN
      amplification, we analyzed MYCN amplification in stored blood plasma samples.
      METHODS: We used quantitative real-time PCR to determine MYCN copy numbers in
      plasma-derived DNA of 10 healthy volunteers and 50 neuroblastoma cases. The copy
      number was calculated as the ratio of copies of MYCN to those of a reference
      gene. Plasma samples obtained after surgery or neoadjuvant therapy were also
      analyzed in five cases and four cases, respectively. RESULTS: In 34 neuroblastoma
      cases, MYCN was nonamplified in both tumor tissue and blood plasma. In 16
      neuroblastoma cases, MYCN was amplified in both tumor tissue and blood plasma; 13
      of the 16 cases showed poor outcomes. MYCN amplification was undetectable in
      blood plasma shortly after surgery or neoadjuvant therapy. The correlation
      coefficient between MYCN copy numbers in tumor tissue and in blood plasma was
      approximately 0.9. CONCLUSION: We can detect MYCN amplification of tumor tissue
      noninvasively and quantitatively by measuring the MYCN copy number in blood
      plasma. Determination of MYCN copy number in plasma may be useful when evaluating
      surgery and neoadjuvant chemotherapy.

PMID- 24022279
TI  - Nurses and our nursing care team members.

PMID- 24022280
TI  - Promoting wellness and being healthy.

PMID- 24022281
TI  - Relationships among work stress, job satisfaction, mental health, and healthy
      lifestyle behaviors in new graduate nurses attending the nurse athlete program: a
      call to action for nursing leaders.
AB  - BACKGROUND: Although nurses are educated to take outstanding care of others, they
      themselves often have poor health outcomes, including high rates of depression
      and obesity, which are associated with stressful work environments. Furthermore,
      a high percentage of new graduate nurses leave their positions in the first year
      of employment, resulting in exorbitant costs to health care systems. PURPOSE: The
      aim of this study was to determine the relationships among key variables that
      influence job satisfaction and healthy lifestyle behaviors of new graduate
      nurses, including workplace stress, work environment, lifestyle beliefs, and
      mental health. DESIGN: A descriptive correlational design was used with baseline
      data from 61 new graduate nurses attending the 2-day Nurse Athlete program, a
      workshop that focuses on nutrition, energy management, and physical activity.
      RESULTS: Higher levels of workplace stress were associated with higher levels of
      depression and anxiety as well as lower levels of resiliency, job satisfaction,
      and healthy lifestyle beliefs. IMPLICATIONS: Nurse leaders and managers must
      invest in creating healthy work environments for new and experienced nurses as
      well as provide mental health screening, resources, and intervention programs
      that focus on education and skills-building in health promoting behaviors,
      including emotional regulation of stress, anxiety, and depression.

PMID- 24022282
TI  - Helping nurses care for self, family, and patients through the nurses living fit
      intervention.
AB  - BACKGROUND: More than half of United States nurses are estimated to be overweight
      or obese. Interventions are needed that help nurses live healthier lifestyles.
      With most registered nurses being female and with an average age of 45.5 years in
      the category most likely to be obese, it is not promising that US nurses will
      become healthier over time without intervention. The Nurses Living Fit (NLF)
      program, an exercise- and nutrition-based intervention innovated by nurses, was
      developed to decrease body mass index in nurse participants and to help nurse's
      care for themselves and their families and patients. SUBJECTS: A total of 217
      nurses self-selected to the NLF intervention (n = 108) or contrast (no
      intervention; n = 109) groups. METHODS: The NLF program included exercise (12
      once-weekly sessions, 1 hour each), yoga (4 once-monthly sessions, 1 hour each),
      nutrition education (4 once-monthly sessions, 1 hour each taught by registered
      dietitians), diary completion (completed daily for 4 weeks specifying time spent
      on exercise/yoga, types and amount of food consumed, amount of water consumed,
      and hours slept), and healthy lifestyle principles education. Evaluation of the
      NLF program components was also completed. RESULTS: The NLF participants had
      significant decreases in body mass index (NLF = -0.5 kg/m; contrast = -0.2 kg/m)
      and waist circumference (NLF = -0.9 in; contrast = -0.2 in). Overall, program
      component evaluation demonstrated that participants wanted more personalized
      exercise, more nutrition education, and year-round program provision. As a result
      of the NLF program, nurses specified they exercised more and improved nutrition.
      CONCLUSIONS: Evidence-based intervention or programs are needed to educate nurses
      on healthy lifestyles. Nurse leaders need to promote healthy workplace
      environments, which can be done in part through the facilitation of exercise- and
      nutrition-based programs, such as NLF, to help nurses better care for themselves
      and their families and patients.

PMID- 24022283
TI  - We cannot ignore nurses' health anymore: a synthesis of the literature on
      evidence-based strategies to improve nurse health.
AB  - Nurses are known to suffer from health problems because of the physical and
      stressful nature of nurses' work. With the advent of health care reform and the
      increasing importance of nurses to quality and cost-effective health care, the
      health of nurses can no longer be ignored. The purpose of this synthesis of the
      literature is to determine what interventions and evidence-based practices have
      been found that support and improve the health of nurses. Whittemore and Knafl's
      integrative review methodology was chosen to guide the synthesis. Eighteen
      studies, all conducted in clinical settings, were identified. Interventions
      included on-site wellness, ergonomic and exercise programs; holistic practices,
      including Tai Chi and massage; the use of clinical supervision; mental health
      programs; and the use of minimal, no lift and lift-team programs. There is a
      critical need for more research specifically designed to improve the health and
      safety of the nursing workforce. 

PMID- 24022284
TI  - Hope for the future: intensifying spirituality in the workplace.
AB  - Healthy workplaces address various issues. Work focused on ergonomics addresses
      physical issues, satisfaction surveys reveal psychosocial issues; and other
      approaches address spirituality issues. Spirituality in the workplace contributes
      to holistic care and to the worth of the individual. Incorporating the concept of
      spirituality, in its broad sense, into the workplace enriches leadership practice
      and contributes to a holistic work environment. Spirituality is core to the
      servant leader approach to leadership and beneficial to other approaches.
      Followers benefit from a holistic approach to leadership; and some specific
      practices can exhibit the belief an organization holds related to the worth of
      the individual. Incorporating spirituality into an organization reflects the same
      values nursing holds for person-centered care, a view of integration of physical,
      psychological, and spiritual needs. 

PMID- 24022285
TI  - Nurse managers describe their practice environments.
AB  - Hospital work environments that support the professional practice of nurses are
      critical to patient safety. Nurse managers are responsible for creating these
      professional practice environments for staff nurses, yet little is known about
      the environments needed to support nurse managers. Domains of nurse managers'
      practice environment have recently been defined. This is a secondary analysis of
      2 cross-sectional studies of organizational characteristics that influence nurse
      manager practice. Content analysis of the free text comments from 127 nurse
      managers was used to illustrate the 8 domains of nurse managers' practice
      environments. Nurse managers valued time spent with their staff; therefore,
      workloads must permit meaningful interaction. Directors demonstrated trust when
      they empowered nurse managers to make decisions. Administrative leaders should
      build patient safety cultures on the basis of shared accountability and mutual
      respect among the health care team. The expectations of nurse managers have
      greatly expanded in the volume and complexity of direct reports, patient care
      areas, and job functions. The nurse managers in this analysis reported
      characteristics of their practice environments that limit their role
      effectiveness and may negatively impact organizational performance. Further
      research is needed to understand the effects of nurse managers' practice
      environments on staff and patient outcomes. 

PMID- 24022286
TI  - Developing a systemic program for compassion fatigue.
AB  - The effort in hospitals to improve the patient experience has yielded a new
      impetus to address compassion fatigue (CF), a combination of secondary traumatic
      stress and burnout. Over the last 3 years, Barnes-Jewish Hospital has developed a
      systemic program for CF resiliency. An initial evaluation of the extent to which
      CF was affecting the hospital's oncology staff led to the formal implementation
      of a resiliency program for oncology registered nurses. The success of that
      program ultimately led to the implementation of a hospital-wide resiliency
      program, designed to help professional caregivers understand CF, recognize the
      physical, mental, and emotional effects of stress, and adopt resiliency
      strategies. The voluntary program has been very well received by participants,
      and a formal evaluation shows promising results with a decline in secondary
      traumatic stress and burnout among participants. Developing an institutional
      culture of recognition and support for CF is critical for health care
      organizations. Establishing such a culture may help managers proactively create
      work environments that provide opportunities for connection and support among
      staff. Compassion fatigue training allows professional caregivers to reconnect to
      their personal mission and then truly begin to connect with an organization's
      values and mission. 

PMID- 24022287
TI  - Combating compassion fatigue: an exemplar of an approach to nursing renewal.
AB  - Compassion fatigue is a phenomenon commonly experienced by nurses. The cumulative
      emotional burden of caring for critically ill patients and their families,
      coupled with the increasing complexity of the health care practice environment,
      significantly drives the experience of compassion fatigue. Compassion fatigue can
      negatively impact nurses' physical and emotional well-being. If left unaddressed,
      compassion fatigue can lead to burnout among nurses. Burnout has been correlated
      to increased patient mortality, increased infection rates, and decreased patient
      satisfaction. In addition, it causes nurses to leave the nursing profession.
      Opportunities for nursing renewal, coupled with a leadership culture that values
      renewal practices, could combat the negative effects of compassion fatigue. A
      Center for Nursing Renewal was created at the Hospital of the University of
      Pennsylvania in Philadelphia, Pennsylvania, to provide a variety of renewal
      opportunities for nurses. This center is supported by a nursing culture that
      recognizes the ill effects of compassion fatigue and promotes wellness and
      renewal practices among nurses. 

PMID- 24022288
TI  - Nurse manager engagement: what it means to nurse managers and staff nurses.
AB  - OBJECTIVE: To describe what nurse manager engagement means to nurse managers and
      staff nurses by incorporating an organizational dashboard to document engagement
      outcomes. BACKGROUND: Retaining engaged nurse managers is crucial for individual
      performance and organizational outcomes. However, nurse manager engagement is
      currently underreported in the literature. METHODS: Existing data from the 2010
      Employee Opinion Survey at the Baylor University Medical Center in Dallas, Texas,
      were used to measure staff engagement among 28 nurse managers and 1497 staff
      nurses. RESULTS: The data showed a 21% gap between manager and staff nurse
      engagement levels, with managers showing higher engagement levels than staff. No
      clear depiction of nurse manager engagement emerged. Consequently, an expanded
      definition of nurse manager engagement was developed alongside a beginning
      dashboard of engagement outcomes. CONCLUSIONS: The findings have implications for
      overcoming barriers that affect staff nurse engagement, improving outcomes, and
      creating definitions of nurse manager engagement.

PMID- 24022289
TI  - Leading change to create a healthy and satisfying work environment.
AB  - Nurse executives must take a leadership role in creating a healthy work
      environment for nurses and all disciplines. Engaging in partnerships and
      empowering clinical nurses to construct the solutions to barriers that may stand
      in the way of the goal of a satisfied and healthy workforce are important
      strategies toward success. This publication outlines many projects a 3-time
      Magnet-designated academic hospital has implemented, working with our shared
      leadership councils, to meet the standards for a healthy work environment. These
      initiatives, from the unit to the hospital level, included standardizing a
      culture change of uninterrupted meal breaks, the creation of intensive care unit
      Zen rooms, strategies to better manage increased patient volumes, best practices
      for facility design, enhancing physician-nurse relations, and a hospital wellness
      program. Data were benchmarked against national nurse and employee surveys to
      compare progress and report outcomes. Two important nursing organization
      structures that have contributed to the success of a healthy and satisfied
      nursing work environment include UEXCEL, a longstanding clinical nurse
      professional practice program, and the hospital's 11-year participation in the
      University HealthSystem Consortium/American Association of Colleges of Nursing
      National Post-Baccalaureate Nurse Residency Program. A highly engaged, well
      educated, and committed nursing workforce, nurtured by a strong leadership team,
      has created a positive work environment characterized by low turnover and high
      retention. 

PMID- 24022290
TI  - Healthy work environments and staff nurse retention: the relationship between
      communication, collaboration, and leadership in the pediatric intensive care
      unit.
AB  - BACKGROUND: A healthy work environment can improve patient outcomes and
      registered nurse (RN) turnover. Creating cultures of retention and fostering
      healthy work environments are 2 major challenges facing nurse leaders today.
      SPECIFIC AIMS: Examine the effects of the healthy work environment
      (communication, collaboration, and leadership) on RN turnover from data collected
      from a research study. METHODS: Descriptive, cross-sectional, correlational
      design. Pediatric critical care RNs from 10 pediatric intensive care units (PICU)
      completed the Practice Environment Scale of the Nursing Work Index Revised and a
      subscale of the Intensive Care Unit Nurse-Physician Communication Questionnaire.
      These staff nurses were asked whether they intend to leave their current job in
      the next 6 months. Statistical analysis included correlations, multiple linear
      regression, t tests (2-tailed), and 1-way analysis of variance. RESULTS: A total
      of 415 RNs completed the survey. There was a statistically significant
      relationship between leadership and the intent to leave (P < .05). There was also
      an inverse relationship between years of experience and intent to leave. None of
      the communication variables between RNs and among RNs and MDs or collaboration
      were significantly associated with PICU nurses' intention to leave. CONCLUSION:
      Effective leadership in the PICU is important to PICU RNs and significantly
      influences their decisions about staying in their current job.

PMID- 24022291
TI  - Staffing healthy workplaces: some global nursing shortage issues.

PMID- 24022292
TI  - Creating and sustaining peace within for the journey of nursing leadership.
AB  - Peace within self or an inner calmness may be created and sustained by caring for
      self at a deep level, committing to an inner journey, and by dedication to
      maintaining a practice of self-care. Suggestions for creating and sustaining
      peace within self, using the model "Listen, Envision and Take Action" (LET or
      allow), are explored as a guide to support and maintain an inner journey. The
      authors describe how a peaceful presence may guide the journey of nursing
      leadership. Along the path of self-care focused on the inner journey, the nursing
      leader may experience enhanced health, self-knowledge, resilience, and a
      transformation of relationships personally and professionally. As nursing
      leaders' role model care for self in the workplace, the organization may
      experience an increase in nurse satisfaction. 

PMID- 24022293
TI  - Single-crystal caged gold nanorods with tunable broadband plasmon resonances.
AB  - We report on the synthesis and characterization of single-crystal caged gold
      nanorods (CGNRs) which exhibited broadband plasmonic resonances. Redshift of
      plasmon resonance can be realized by increasing the length, whereas blueshift can
      be achieved by increasing either the overall width of the cage or the thickness
      of nanocage walls. 

PMID- 24022294
TI  - Trans effect and trans influence: importance of metal mediated ligand-ligand
      repulsion.
AB  - The trans effect and trans influence were investigated and rationalized in the
      aminolysis, a typical nucleophilic substitution reaction, of trans-TPtCl2NH3
      complexes (T = NH3, PH3, CO and C2H4) using energy decomposition analysis, both
      along the reaction paths and on the stationary points, and Natural Orbital for
      Chemical Valence analysis. In order to scrutinize the underlying principles and
      the origin of the kinetic trans effect, plausible structural constraints were
      introduced in the decomposition analysis, which allowed eliminating the distance
      dependence of the interaction energy components. It was established that the
      trans effect can be rationalized with the interaction of the TPtCl2 and NH3
      fragments in the reactant state and TPtCl2 and (NH3)2 fragments in the transition
      state. It was evinced quantitatively that the sigma-donor ability of T indeed
      controls the stability of the reactant, whereas in the case of pi-acids,
      backdonation stabilizes the transition state, for which conceptually two
      mechanisms are available: intrinsic and induced pi-backdonation. In the
      destabilization of the reactant and also in the labilization of the leaving group
      (trans influence) repulsion plays a more important role than orbital sharing
      effects, which are the cornerstones of the widely accepted interpretations of the
      trans influence, such as competition for donation or limitation of the donation
      of the leaving group by the trans ligand T. This repulsive interaction was
      rationalized both in terms of donated electron density and also in the molecular
      orbital framework. NOCV orbitals indeed clearly show that the sigma-trans effect
      can be envisioned as a donation from the trans ligand not only to the metal but
      also to the sigma* orbital of the metal-leaving group bond, which manifests as a
      repulsion between the metal and the leaving group. 

PMID- 24022295
TI  - A fast multilocus test with adaptive SNP selection for large-scale genetic
      association studies.
AB  - As increasing evidence suggests that multiple correlated genetic variants could
      jointly influence the outcome, a multilocus test that aggregates association
      evidence across multiple genetic markers in a considered gene or a genomic region
      may be more powerful than a single-marker test for detecting susceptibility loci.
      We propose a multilocus test, AdaJoint, which adopts a variable selection
      procedure to identify a subset of genetic markers that jointly show the strongest
      association signal, and defines the test statistic based on the selected genetic
      markers. The P-value from the AdaJoint test is evaluated by a computationally
      efficient algorithm that effectively adjusts for multiple-comparison, and is
      hundreds of times faster than the standard permutation method. Simulation studies
      demonstrate that AdaJoint has the most robust performance among several commonly
      used multilocus tests. We perform multilocus analysis of over 26,000
      genes/regions on two genome-wide association studies of pancreatic cancer.
      Compared with its competitors, AdaJoint identifies a much stronger association
      between the gene CLPTM1L and pancreatic cancer risk (6.0 * 10(-8)), with the
      signal optimally captured by two correlated single-nucleotide polymorphisms
      (SNPs). Finally, we show AdaJoint as a powerful tool for mapping cis-regulating
      methylation quantitative trait loci on normal breast tissues, and find many CpG
      sites whose methylation levels are jointly regulated by multiple SNPs nearby.

PMID- 24022297
TI  - Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: functional
      consequences of four CYP11B1 mutations.
AB  - Congenital adrenal hyperplasia (CAH) is one of the most common autosomal
      recessive inherited endocrine disease. Steroid 11beta-hydroxylase deficiency
      (11beta-OHD) is the second most common form of CAH. The aim of the study was to
      study the functional consequences of three novel and one previously described
      CYP11B1 gene mutations (p.(Arg143Trp), p.(Ala306Val), p.(Glu310Lys) and
      p.(Arg332Gln)) detected in patients suffering from classical and non-classical
      11beta-OHD. Functional analyses were performed by using a HEK293 cell in vitro
      expression system comparing wild type (WT) with mutant 11beta-hydroxylase
      activity. Mutant proteins were examined in silico to study their effect on the
      three-dimensional structure of the protein. Two mutations (p.(Ala306Val) and
      p.(Glu310Lys)) detected in patients with classical 11beta-OHD showed a nearly
      complete loss of 11beta-hydroxylase activity. The mutations p.(Arg143Trp) and
      p.(Arg332Gln) detected in patients with non-classical 11beta-OHD showed a partial
      functional impairment with approximately 8% and 6% of WT activity, respectively.
      Functional mutation analysis allows the classification of novel CYP11B1 mutations
      as causes of classical and non-classical 11beta-OHD. The detection of patients
      with non-classical phenotypes underscores the importance to screen patients with
      a phenotype comparable to non-classical 21-hydroxylase deficiency for mutations
      in the CYP11B1 gene in case of a negative analysis of the CYP21A2 gene. As
      CYP11B1 mutations are most often individual for a family, the in vitro analysis
      of novel mutations is essential for clinical and genetic counselling. 

PMID- 24022296
TI  - Allele-specific Col1a1 silencing reduces mutant collagen in fibroblasts from Brtl
      mouse, a model for classical osteogenesis imperfecta.
AB  - Gene silencing approaches have the potential to become a powerful curative tool
      for a variety of monogenic diseases caused by gain-of-function mutations.
      Classical osteogenesis imperfecta (OI), a dominantly inherited bone dysplasia, is
      characterized in its more severe forms by synthesis of structurally abnormal type
      I collagen, which exerts a negative effect on extracellular matrix. Specific
      suppression of the mutant (Mut) allele would convert severe OI forms to the mild
      type caused by a quantitative defect in normal collagen. Here, we describe the in
      vitro and ex vivo investigation of a small interfering RNA (siRNA) approach to
      allele-specific gene silencing using Mut Col1a1 from the Brtl mouse, a well
      characterized model for classical human OI. A human embryonic kidney cell line,
      which expresses the firefly luciferase gene, combined with either wild-type or
      Mut Brtl Col1a1 exon 23 sequences, was used for the first screening. The siRNAs
      selected based on their specificity and the corresponding short hairpin RNAs
      (shRNAs) subcloned in a lentiviral vector were evaluated ex vivo in Brtl
      fibroblasts for their effect on collagen transcripts and protein. A preferential
      reduction of the Mut allele of up to 52% was associated with about 40% decrease
      of the Mut protein, with no alteration of cell proliferation. Interestingly, a
      downregulation of HSP47, a specific collagen chaperone known to be upregulated in
      some OI cases, was detected. Our data support further testing of shRNAs and their
      delivery by lentivirus as a strategy to specifically suppress the Mut allele in
      mesenchymal stem cells of OI patients for autologous transplantation. 

PMID- 24022299
TI  - Inconsistent inheritance of telomere length (TL): is offspring TL more strongly
      correlated with maternal or paternal TL?

PMID- 24022298
TI  - Offering prenatal diagnostic tests: European guidelines for clinical practice
      [corrected].
AB  - For over four decades, it has been possible to offer prenatal diagnostic testing
      for fetal abnormalities. Prenatal testing is now available for a wide range of
      monogenic disorders as well as chromosomal abnormalities and should be provided
      within the ethical framework of informed consent and autonomous choice. However,
      there are no published guidelines for health professionals from varied
      disciplines who offer prenatal diagnosis (PND) in a range of possible settings
      including departments of maternity, obstetrics and clinical genetics. We used an
      Expert Group technique to develop a set of guidelines for provision of prenatal
      diagnostic services. Thirteen European health professionals, all experts in PND,
      participated in a workshop to develop the guidelines, which were then subjected
      to a wide consultation process. The objective of PND was defined as providing
      prenatal diagnostic testing services (for genetic conditions) that enable
      families to make informed choices consistent with their individual needs and
      values and which support them in dealing with the outcome of such testing.
      General principles, logistical considerations, clinical care and counselling
      topics are all described and are equally applicable to invasive and non-invasive
      testing. These guidelines provide a framework for ethical clinical care; however,
      they are flexible enough to enable practitioners to adapt them to their
      particular setting. Ideally, an individualised approach to each family is
      required to ensure autonomous choice and informed consent regarding prenatal
      diagnostic testing within the local ethical and legal framework. 

PMID- 24022300
TI  - Variants at IRX4 as prostate cancer expression quantitative trait loci.
AB  - Genome-wide association studies (GWAS) have identified numerous prostate cancer
      associated risk loci. Some variants at these loci may be regulatory and influence
      expression of nearby genes. Such loci are known as cis-expression quantitative
      trait loci (cis-eQTL). As cis-eQTLs are highly tissue-specific, we asked if GWAS
      identified prostate cancer risk loci are cis-eQTLs in human prostate tumor
      tissues. We investigated 50 prostate cancer samples for their genotype at 59
      prostate cancer risk-associated single-nucleotide polymorphisms (SNPs) and
      performed cis-eQTL analysis of transcripts from paired primary tumors within two
      megabase windows. We tested 586 transcript-genotype associations, of which 27
      were significant (false discovery rate <=10%). An equivalent eQTL analysis of the
      same prostate cancer risk loci in lymphoblastoid cell lines did not result in any
      significant associations. The top-ranked cis-eQTL involved the IRX4 (Iroquois
      homeobox protein 4) transcript and rs12653946, tagged by rs10866528 in our study
      (P=4.91 * 10(-5)). Replication studies, linkage disequilibrium, and imputation
      analyses highlight population specificity at this locus. We independently
      validated IRX4 as a potential prostate cancer risk gene through cis-eQTL analysis
      of prostate cancer risk variants. Cis-eQTL analysis in relevant tissues, even
      with a small sample size, can be a powerful method to expedite functional follow
      up of GWAS. 

PMID- 24022303
TI  - Parental mosaicism is a pitfall in preimplantation genetic diagnosis of dominant
      disorders.
AB  - PCR amplification on single cells is prone to allele drop-out (PCR failure of one
      allele), a cause of misdiagnosis in preimplantation genetic diagnosis (PGD).
      Owing to this error risk, PGD usually relies on both direct and indirect genetic
      analyses. When the affected partner is the sporadic case of a dominant disorder,
      building haplotypes require spermatozoon or polar body testing prior to PGD, but
      these procedures are cost and time-consuming. A couple requested PGD because the
      male partner suffered from a dominant Cowden syndrome (CS). He was a sporadic
      case, but the couple had a first unaffected child and the non-mutated paternal
      haplotype was tentatively deduced. The couple had a second spontaneous pregnancy
      and the fetus was found to carry the at-risk haplotype but not the PTEN mutation.
      The mutation was present in blood from the affected father, but at low level,
      confirming the somatic mosaicism. Ignoring the possibility of mosaicism in the CS
      patient would have potentially led to selection of affected embryos. This
      observation emphasizes the risk of PGD in families at risk to transmit autosomal
      dominant disorder when the affected partner is a sporadic case. 

PMID- 24022301
TI  - Genetic analysis of dyslexia candidate genes in the European cross-linguistic
      NeuroDys cohort.
AB  - Dyslexia is one of the most common childhood disorders with a prevalence of
      around 5-10% in school-age children. Although an important genetic component is
      known to have a role in the aetiology of dyslexia, we are far from understanding
      the molecular mechanisms leading to the disorder. Several candidate genes have
      been implicated in dyslexia, including DYX1C1, DCDC2, KIAA0319, and the
      MRPL19/C2ORF3 locus, each with reports of both positive and no replications. We
      generated a European cross-linguistic sample of school-age children - the
      NeuroDys cohort - that includes more than 900 individuals with dyslexia, sampled
      with homogenous inclusion criteria across eight European countries, and a
      comparable number of controls. Here, we describe association analysis of the
      dyslexia candidate genes/locus in the NeuroDys cohort. We performed both case
      control and quantitative association analyses of single markers and haplotypes
      previously reported to be dyslexia-associated. Although we observed association
      signals in samples from single countries, we did not find any marker or haplotype
      that was significantly associated with either case-control status or quantitative
      measurements of word-reading or spelling in the meta-analysis of all eight
      countries combined. Like in other neurocognitive disorders, our findings
      underline the need for larger sample sizes to validate possibly weak genetic
      effects. 

PMID- 24022302
TI  - Functional analysis of 11 novel GBA alleles.
AB  - Gaucher disease is the most frequent lysosomal storage disorder due to the
      deficiency of the acid beta-glucosidase, encoded by the GBA gene. In this study,
      we report the structural and functional characterization of 11 novel GBA alleles.
      Seven single missense alleles, P159S, N188I, E235K, P245T, W312S, S366R and
      W381C, and two alleles carrying in cis mutations, (N188S; G265R) and (E326K;
      D380N), were studied for enzyme activity in transiently transfected cells. All
      mutants were inactive except the P159S, which retained 15% of wild-type activity.
      To further characterize the alleles carrying two in cis mutations, we expressed
      constructs bearing singly each mutation. The presence of G265R or D380N mutations
      completely abolished enzyme activity, while N188S and E326K mutants retained 25
      and 54% of wild-type activity, respectively. Two mutations, affecting the
      acceptor splice site of introns 5 (c.589-1G>A) and 9 (c.1389-1G>A), led to the
      synthesis of aberrant mRNA. Unpredictably, family studies showed that two alleles
      resulted from germline or 'de novo' mutations. These results strengthen the
      importance of performing a complete and accurate molecular analysis of the GBA
      gene in order to avoid misleading conclusions and provide a comprehensive
      functional analysis of new GBA mutations. 

PMID- 24022304
TI  - Low-cost and high-performance CoMoS4 and NiMoS4 counter electrodes for dye
      sensitized solar cells.
AB  - Porous chalcogels CoMoS4 and NiMoS4 made by a facile solution reaction displayed
      good electrocatalytic activity in the redox reaction of the I(-)/I3(-) shuttle.
      Dye-sensitized solar cells with these ternary compounds as counter electrodes
      (CEs) showed photovoltaic performance similar to the devices made with noble
      metal platinum CE (7.46%). 

PMID- 24022305
TI  - The cell block method increases the diagnostic yield in exudative pleural
      effusions accompanying lung cancer.
AB  - OBJECTIVE: Thoracentesis is the first investigation to be performed in a patient
      with lung cancer and pleural effusion. The diagnostic yield of conventional smear
      studies varies in the first thoracentesis. In this study, we aimed to investigate
      if the cell block method increases the diagnostic yield in exudative pleural
      effusions accompanying lung cancer. MATERIAL AND METHOD: Forty patients with lung
      cancer and exudative pleural effusions were included. Ten mililiters of fresh
      pleural fluid was obtained by thoracentesis from all patients in the initial
      evaluation. The pleural fluid sample was divided into two equal parts. One part
      was subjected to conventional smear and the other to the cell block method.
      Conventional smears were stained with May-Grunwald-Giemsa and Hematoxylin-Eosin.
      Cell block sections were stained with Hematoxylin-Eosin and mucicarmine.
      Conventional smear findings were grouped as "benign cytology" or "malignant
      cytology". Th e cell block sections were evaluated for the presence of single
      tumor cells, acinary or papillary pattern, solid islands and staining with
      mucicarmine. RESULTS: There were 20 patients each in the benign and malignant
      conventional smear group. In the benign group, adding the cell block method to
      conventional smear provided a diagnosis of malignancy in 4 more patients and the
      diagnosis of malignant effusion was increased by a ratio of 10% (4/40). In the
      malignant group, adding the cell block technique provided the subtyping of lung
      cancer as adenocarcinoma in 7 patients (7/20, 35%). CONCLUSION: Our study
      confirms that the cell block method combined with conventional smear increases
      the diagnostic yield in exudative pleural effusions accompanying lung cancer.

PMID- 24022306
TI  - Predictive value of micronucleus count in cervical intraepithelial neoplasia and
      carcinoma.
AB  - OBJECTIVE: A micronucleus is a small additional nucleus formed due to chromosomal
      loss or fragmentation. The aim of this study was to assess the utility of
      micronucleus count as a screening tool in cervical cancer. MATERIAL AND METHOD: A
      total of 132 cases consisting of 42 pre-neoplastic and neoplastic cases and 90
      non-neoplastic cases were studied. Only routine Papanicolaou-stained cervical
      smears were used. In each smear, the number of micronucleated cells and
      binucleated cells were counted under oil immersion and expressed as a count per
      1,000 cells. The micronucleated and binucleated cell counts in pre-neoplastic,
      neoplastic and non-neoplastic categories were compared for statistical
      significance. The counts were also correlated with age, duration of marital life,
      number of pregnancies and abortions. RESULTS: The micronucleus count and the
      binucleated cell count were significantly higher in the high -grade squamous
      intraepithelial lesion (HSIL) and invasive carcinoma categories compared to low 
      grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver
      operating characteristic (ROC) curve analysis revealed that micronucleus count
      and binucleated cell count possess a high degree of sensitivity and specificity
      for identifying HSIL and invasive carcinoma. CONCLUSION: Our results reveal that
      micronucleus evaluation in routine Pap smears is a very useful biomarker in
      cervical cancer screening. The binucleated cell count increases the predictive
      value of this simple test.

PMID- 24022307
TI  - Patients with epithelial cell abnormality in PAP smears: correlation of results
      with follow-up smears and cervical biopsies.
AB  - OBJECTIVE: Cervical carcinoma has been included in the preventable diseases
      category ever since the use of cervical cytology in routine practice. The Pap
      test is an efficient screening test. We aimed to compare the cervical cytology
      diagnosis with biopsy and smear follow up results in our institution. MATERIAL
      AND METHOD: We aimed to compare the diagnosis of cytology material examined in
      our institution during the 2009-2012 period with their biopsy and smear follow
      ups. The diagnoses were compared with the follow up smears and/or cervical
      biopsies. RESULTS: 13610 Pap tests were examined during September 2009-July 2012.
      Among these cases, there were 370 atypical squamous cells of undetermined
      significance (ASCUS), 29 atypical squamous cells-high grade intraepithelial
      lesions cannot be excluded (ASC-H), 155 low grade squamous intraepithelial lesion
      (LSIL), 33 high grade squamous intraepithelial lesion (HSIL), and 5 atypical
      glandular cell (AGC) diagnoses. The ratio of atypical squamous cell (ASCUS and
      ASC-H) to squamous intraepithelial lesions was 2.12. Squamous intraepithelial
      lesion was verified in 47 of 91 ASCUS cases. Among patients who had a cervical
      biopsy, 52 of 64 LSIL cases and all of the 21 HSIL cases had biopsy-proven SIL.
      CONCLUSION: Atypical squamous cell (ASC) is the most common diagnosis in abnormal
      cervical cytology. As it is indefinite, ASC is used as a quality assurance
      parameter and the aim is to decrease its use. As the ratio of epithelial cell
      abnormality is variable in different populations, the ASC/SIL is a more definite
      variable to be used for quality assurance. The efficiency in clinical use of the
      cervical cytology screening test is determined by biopsy verification. Our
      epithelial cell abnormality, ASC/SIL ratio and cytology-histology correlation
      values were parallel to the literature, proving that the methods are used
      reliably at our institution.

PMID- 24022308
TI  - Comparison of growth hormone receptor, igf-1r and igfbp-3 between tumoral and non
      tumoral areas in non-melanoma skin cancers.
AB  - OBJECTIVE: A relationship between the pathogenesis of some cancers and growth
      hormone, insulin-like growth factor-1 and insulin-like growth factors binding
      protein-3 has been shown. Our aim was to evaluate the expression of growth
      hormone receptor, insulin-like growth factor-1 receptor and insulin-like growth
      factors binding protein-3 in actinic keratosis, basal cell carcinoma and squamous
      cell carcinoma, and to compare the expression patterns of tumoral areas with
      normal epidermis and skin appendages. MATERIAL AND METHOD: The formalin-fixed,
      paraff in-embedded tissues of 40 patients which were diagnosed as 15 actinic
      keratosis, 15 basal cell carcinoma and 15 squamous cell carcinoma were analyzed
      for growth hormone receptor, insulin-like growth factor-1 receptor and insulin
      like growth factors binding protein-3 with the immunohistochemical method using
      the streptavidin-biotin-peroxidase technique. RESULTS: There was no difference
      between tumoral areas of actinic keratosis, basal cell carcinoma and squamous
      cell carcinoma in expression of growth hormone receptor and insulin-like growth
      factors binding protein-3 (P > 0.05). However, a significantly higher expression
      of insulin-like growth factor-1 receptor was observed in tumoral areas of
      squamous cell carcinoma (P < 0.01). In basal cell carcinoma, a significantly
      lower intensity of immunostaining with growth hormone receptor, insulin-like
      growth factor-1 receptor and insulin-like growth factors binding protein-3 in
      tumoral areas than skin appendages was seen (P < 0.01). In squamous cell
      carcinoma, higher expressions of growth hormone receptor, insulin-like growth
      factor-1 receptor and insulin-like growth factors binding protein-3 in tumoral
      areas than peritumoral epidermis was found (P =0.06, P < 0.01 and P =0.02,
      respectively). CONCLUSION: Our study points out that, growth hormone receptor,
      insulin-like growth factor-1 receptor and insulin-like growth factors binding
      protein-3 have a role in the pathogenesis of non-melanoma skin cancers,
      especially squamous cell carcinoma.

PMID- 24022309
TI  - Assessment of maturation status of tumor-infiltrating dendritic cells in invasive
      ductal carcinoma of the breast: relation with vascular endothelial growth factor
      expression.
AB  - OBJECTIVE: Poor immunogenicity has been described in breast carcinoma although
      dendritic cells, the major antigen presenters, are known to infiltrate the tumor.
      Vascular endothelial growth factor has been proposed to reduce local immune
      response in tumors. We investigated the maturation status of dendritic cells in
      invasive ductal carcinoma of the breast in relation to vascular endothelial
      growth factor expression and clinicopathological parameters. MATERIAL AND METHOD:
      Fifty invasive ductal carcinomas of the breast were immunostained with CD1a
      (marker of immature dendritic cells); CD83 (marker of mature dendritic cells),
      vascular endothelial growth factor, estrogen receptor and progesterone receptor.
      RESULTS: Mature dendritic cells were detected in 36 cases (72%), and correlated
      with smaller tumor size, negative lymph nodes, positive steroid receptor status,
      and lower grade (P < 0.001). Immature dendritic cells were found in 100% of cases
      and correlated only with negative steroid receptor expression (estrogen receptor
      and progesterone receptor) (P=0.006 and 0.020 respectively). Vascular endothelial
      growth factor expression was detected in 44 cases (88%), and correlated directly
      with positive nodal metastases (P=0.014), correlated inversely with mature
      dendritic cell count (P=0.005); and did not correlate with immature dendritic
      cell count (P=0.104). CONCLUSION: Mature dendritic cell count correlates with
      good prognostic features in invasive ductal carcinoma of the breast, suggesting
      their role in initiating primary anti-tumor immune response. Vascular endothelial
      growth factor expression may play a role in inhibition of dendritic cell
      maturation sequence in the tumor microenvironment.

PMID- 24022310
TI  - The approaches of physicians working in the field of pathology regarding forensic
      pathology practice and the training process.
AB  - OBJECTIVE: Forensic autopsies are performed by the forensic medicine department
      and the microscopic examination processes by pathology specialists within the
      forensic medicine practice in Turkey. This disconnection in the process raises
      problems in the training of both branches. The aim of this study was to determine
      the awareness of pathology staff on forensic medicine practices and
      responsibilities and their opinion on the pathology training model in the
      forensic medicine specialty and to discuss the matter within the framework of the
      present situation and global applications. MATERIAL AND METHOD: A 15-item
      questionnaire form distributed to the participant physicians during registration
      at the 21st National Pathology Congress held in 2011 was evaluated. RESULTS: 94
      participants responded. A negative opinion was expressed by 72% about the
      interest in the general post-mortem process. The view that pathology specialists
      should undergo a separate training to perform autopsies was predominant and there
      was a general lack of interest in all kinds of autopsy processes. The percentage
      who said they knew the legal responsibility of a pathology specialist regarding
      forensic autopsies correctly was 37%. The questions "what are the necessary
      factors to contribute to the pathology training in forensic medicine" and "if
      anything is required, which of them would take priority" were respectively
      answered as "for me to be interested (46%)" and "a system guaranteeing that
      training will always be given by pathology specialists (67%)". Despite the
      possibility of becoming a forensic medicine specialist in two years, the mean
      answer score of the participants to the phrase "I do not consider becoming a
      forensic medicine specialist" was 4.1 (out of 5). CONCLUSION: A reluctance among
      the pathologists in our country was seen regarding forensic medicine specialists
      being able to perform post-mortem microscopic examination. However, despite their
      legal responsibilities, their interest in forensic pathology practice was low.
      There seems to be rational factor that would increase this interest in the near
      future. Cooperation is necessary to enable forensic medicine specialists to
      perform post-mortem pathology procedures. This cooperation should be based on
      improving the training of pathology research assistants.

PMID- 24022312
TI  - Cystic solitary fibrous tumor of the liver: a case report.
AB  - Solitary fibrous tumors are unusual neoplasms that are rarely found in the liver
      parenchyma. They are usually described as hard, grayish white, well-defined
      lesions. Predominant cystic change in a solitary fibrous tumor is an unexpected
      finding, with only a few previous cases reported in the literature, two of which
      are localized in the head and neck region. Herein, we report a unique case of
      solitary fibrous tumor of the liver in a 38-year-old female with predominant
      multiloculated cystic appearance, and discuss the histopathologic differential
      diagnosis. 

PMID- 24022313
TI  - Spindle cell rhabdomyosarcoma displaying CD34 positivity: a potential diagnostic
      pitfall; report of two pediatric cases.
AB  - Spindle cell rhabdomyosarcoma is a rare subtype of rhabdomyosarcoma mainly seen
      in children. Occasional aberrant staining with a variety of immunohistochemical
      markers has been noted. The aberrantly expressed markers include alpha-smooth
      muscle actin, cytokeratin, S100, neurofilaments, CD20, immunoglobins, and CD117.
      We report herein two pediatric cases displaying strong CD34 positivity and one
      with additional focal CD117 positivity, causing considerable difficulty in
      distinction from solitary fibrous tumor and extra-gastrointestinal stromal tumor.
      To our knowledge, CD34 staining has been merely reported in rhabdomyosarcoma.
      Spindle cell rhabdomyosarcoma has to be considered in the differential diagnosis
      of childhood spindle cell tumors. Post-chemotherapy specimens should be evaluated
      in caution, since chemotherapy can cause considerable changes in tumor antigen
      expression. Since CD117 and CD34 are stem cell markers, their positivity in
      pediatric tumors should be interpreted with caution. Even if the morphology is
      not supportive, a wide immunohistochemical panel should be applied in childhood
      malignant solid tumors. 

PMID- 24022311
TI  - HPV types in Turkey: multicenter hospital based evaluation of 6388 patients in
      Turkish gynecologic oncology group centers.
AB  - OBJECTIVE: To evaluate the prevalence of HPV DNA and cervical cytological
      abnormalities, to compare cervical cytology results and HPV DNA and to define HPV
      types distribution in a large series of Turkish women who have undergone HPV
      analysis in hospitals that are members of the Turkish Gynecological Oncology
      Group. MATERIAL AND METHOD: Between 2006 and 2010, a total of 6388 patients' data
      was retrospectively evaluated at 12 healthcare centers in Turkey. Demographic
      characteristics, cervical cytology results, HPV status and types were compared.
      RESULTS: The mean age of the patients was 38.9+/-10.2. Overall, 25% of the women
      were found to be HPV positive. Presence of HPV-DNA among patients with abnormal
      and normal cytology was 52% and 27%, respectively. There was significant
      difference with respect to decades of life and HPV positivity (p < 0.05). HPV was
      positive in (within the HPV (+) patients) 37%, 9%, 27%, 20%, 22%, and 41% of the
      ASCUS, ASC-H, LSIL HSIL, glandular cell abnormalities, and SCC cases respectively
      The most common HPV types in our study were as follows; HPV 16 (32%), HPV 6
      (17%), HPV 11 (9%), HPV 18 (8%), HPV 31 (6%), HPV 51 (5%), HPV 33 (3%).
      CONCLUSION: In this hospital based retrospective analysis, HPV genotypes in
      Turkish women with normal and abnormal cytology are similar to those reported
      from western countries. Further population based prospective multicenter studies
      are necessary to determine non-hospital based HPV prevalence in Turkish women.

PMID- 24022314
TI  - Primary low grade intratesticular leiomyosarcoma: case report and review of the
      literature.
AB  - A 49-year-old male presented with a painful mass in the left scrotum. An inguinal
      orchiectomy was performed. Pathological examination revealed a well
      differentiated leiomyosarcoma completely located inside the testicular
      parenchyma. We report this unusual case because primary leiomyosarcoma of the
      testis proper is extremely rare; our patient being the 19th case recorded thus
      far in the medical literature. It can lead to significant clinical and diagnostic
      difficulty due to its wide differential diagnosis and extreme rarity. 

PMID- 24022315
TI  - Bilateral breast metastasis from mucinous adenocarcinoma of the rectum: a case
      report and review of the literature.
AB  - Metastatic breast carcinoma is rarely seen in clinical practice. It has been
      reported that lymphoma-leukemia, melanoma and sarcomas can metastasize to the
      breast. Bilateral metastases to the breast are rare and commonly have been seen
      to originate from ovarian carcinoma. Adenocarcinoma of rectum metastasizing to
      breast is an extremely rare clinico-pathological situation. We report a 28-year
      old female who presented with bilateral breast metastasis 9 months after abdomino
      perineal resection and total meso-rectal excision for a locally advanced mucinous
      adenocarcinoma of the rectum. A few case reports of a mucinous adenocarcinoma of
      rectum presenting with bilateral breast metastasis have been seen in the world
      literature and we hereby report this case who till now is the youngest patient
      reported. 

PMID- 24022316
TI  - [Oral focal mucinosis: a case report and review of the literature].
AB  - Oral focal mucinosis is a rare clinicopathological entity that represents the
      mucosal counterpart of cutaneous focal mucinosis or cutaneous myxoid cyst. The
      aetiology is unknown. Oral focal mucinosis is most common in young adults. The
      gingiva is the most common site and the hard palate is the second most common
      location. A 19-year-old male patient presented with a 2 cm painless mass
      localized to the palatal side. An excisional biopsy was taken and sent for
      histopathologic evaluation to our department. Histopathologic findings were a
      well-circumscribed lesion composed of myxomatous connective tissue that contained
      bipolar, fusiform or stellate shaped fibroblasts. The aim of this study was to
      bring oral focal musinosis diagnosis to the attention of clinicians and
      pathologists when considering the differential diagnosis of gingival and palatal
      nodules. 

PMID- 24022317
TI  - [Multiloculated epidermoid cyst of spleen: a case report].
AB  - Splenic epidermoid cyst is a rare cystic disease of spleen. Primary cysts of the
      spleen lined by epithelium or endothelium are usually seen in young adults. A 23
      year-old woman with abdominal distension presented at the surgery outpatients of
      our hospital. Splenomegaly was detected on physical examination and elective
      surgery was performed. The multiloculated cyst was 10x6 cm on macroscopic
      examination and creamy material was drained. Immunohistochemical examination of
      the cyst lined with epithelium was Cytokeratin and CEA positive and calretinin,
      BerEP4, HBME-1 and F8 negative and it was reported as 'epidermoid cyst'. We
      discussed the etiopathogenesis of our case in light of the theories regarding its
      development. 

PMID- 24022318
TI  - "Pure" primary large cell neuroendocrine carcinoma of the urinary bladder.

PMID- 24022319
TI  - Comparison of methods for handling missing covariate data.
AB  - Missing covariate data is a common problem in nonlinear mixed effects modelling
      of clinical data. The aim of this study was to implement and compare methods for
      handling missing covariate data in nonlinear mixed effects modelling under
      different missing data mechanisms. Simulations generated data for 200 individuals
      with a 50% difference in clearance between males and females. Three different
      types of missing data mechanisms were simulated and information about sex was
      missing for 50% of the individuals. Six methods for handling the missing
      covariate were compared in a stochastic simulations and estimations study where
      200 data sets were simulated. The methods were compared according to bias and
      precision of parameter estimates. Multiple imputation based on weight and
      response, full maximum likelihood modelling using information on weight and full
      maximum likelihood modelling where the proportion of males among the individuals
      lacking information about sex was estimated (EST) gave precise and unbiased
      estimates in the presence of missing data when data were missing completely at
      random or missing at random. When data were missing not at random, the only
      method resulting in low bias and high parameter precision was EST.

PMID- 24022320
TI  - Stable isotope dilution mass spectrometry for membrane transporter quantitation.
AB  - This review provides an introduction to stable isotope dilution mass spectrometry
      (MS) and its emerging applications in the analysis of membrane transporter
      proteins. Various approaches and application examples, for the generation and use
      of quantitation reference standards-either stable isotope-labeled peptides or
      proteins-are discussed as they apply to the MS quantitation of membrane proteins.
      Technological considerations for the sample preparation of membrane transporter
      proteins are also presented.

PMID- 24022321
TI  - Endogenous fructose production and metabolism in the liver contributes to the
      development of metabolic syndrome.
AB  - Carbohydrates with high glycaemic index are proposed to promote the development
      of obesity, insulin resistance and fatty liver, but the mechanism by which this
      occurs remains unknown. High serum glucose concentrations are known to induce the
      polyol pathway and increase fructose generation in the liver. Here we show that
      this hepatic, endogenously produced fructose causes systemic metabolic changes.
      We demonstrate that mice unable to metabolize fructose are protected from an
      increase in energy intake and body weight, visceral obesity, fatty liver,
      elevated insulin levels and hyperleptinaemia after exposure to 10% glucose for 14
      weeks. In normal mice, glucose consumption is accompanied by aldose reductase and
      polyol pathway activation in steatotic areas. In this regard, we show that aldose
      reductase-deficient mice are protected against glucose-induced fatty liver. We
      conclude that endogenous fructose generation and metabolism in the liver
      represents an important mechanism by which glucose promotes the development of
      metabolic syndrome. 

PMID- 24022322
TI  - Conferring the ability to utilize inorganic polyphosphate on ATP-specific NAD
      kinase.
AB  - NAD kinase (NADK) is a crucial enzyme for production of NADP+. ATP-specific NADK
      prefers ATP to inorganic polyphosphate [poly(P)] as a phosphoryl donor, whereas
      poly(P)/ATP-NADK utilizes both ATP and poly(P), and is employed in industrial
      mass production of NADP+. Poly(P)/ATP-NADKs are distributed throughout Gram
      positive bacteria and Archaea, whereas ATP-specific NADKs are found in Gram
      negative alpha- and gamma-proteobacteria and eukaryotes. In this study, we
      succeeded in conferring the ability to utilize poly(P) on gamma-proteobacterial
      ATP-specific NADKs through a single amino-acid substitution; the substituted
      amino-acid residue is therefore important in determining the phosphoryl-donor
      specificity of gamma-proteobacterial NADKs. We also demonstrate that a
      poly(P)/ATP-NADK created through this method is suitable for the poly(P)
      dependent mass production of NADP+. Moreover, based on our results, we provide
      insight into the evolution of bacterial NADKs, in particular, how NADKs evolved
      from poly(P)/ATP-NADKs into ATP-specific NADKs.

PMID- 24022323
TI  - Atrial fibrillation and prognosis in patients 80+ years old with chronic heart
      failure.
AB  - INTRODUCTION: It is well known that the prevalence of atrial fibrillation (AF)
      increases with age. The purpose was to evaluate the impact of AF at the 1-year
      outcome of patients aged 80? who suffered from chronic heart failure (CHF).
      MATERIALS AND METHODS: The study included 220 consecutive patients at age 80-92
      (mean 82.8 years, 45.5 % men) hospitalized for heart failure. The prospective
      analysis contains demographic and clinical data, basic laboratory tests with
      hsTnT and NT-proBNP, 12-lead resting electrocardiogram, echocardiography and
      coronary angiography results and the number of deaths at the 1-year followup.
      Patients were analyzed depending on AF in the resting electrocardiogram at
      hospital entry. RESULTS: AF was recorded in 52 patients (24 %). The relationship
      with AF was found for more advanced NYHA class III and IV (p?0.001), higher
      concentrations of hsCRP (p = 0.0005), hsTnT (p = 0.007) and NT-proBNP (p =
      0.0098), higher heart rate in the electrocardiogram (p = 0.000) and longer
      hospitalization (p = 0.025), older age (p = 0.003) and lower left ventricular
      ejection fraction (p = 0.006). Annual mortality was 13 % and was higher if AF
      occurred (17 %). However, there was no association between deaths and AF (p =
      0.3297). From the multivariate stepwise analysis, independent risk factors for
      annual mortality were male gender (OR = 3.432; p = 0.043), left ventricular
      systolic dimension (OR = 1.871; p = 0.004) and dyslipidemia (OR = 0.252; p =
      0.043). CONCLUSIONS: In the oldest patients aged 80? who suffered from CHF, the
      incidence of atrial fibrillation and annual mortality was high. The independent
      variables, which enhanced the risk of death at the 1-year follow-up, were male
      sex and left ventricular systolic dimension, but not atrial fibrillation.

PMID- 24022325
TI  - Resting-state functional brain connectivity: lessons from functional near
      infrared spectroscopy.
AB  - Resting-state functional near-infrared spectroscopy (R-fNIRS) is an active area
      of interest and is currently attracting considerable attention as a new imaging
      tool for the study of resting-state brain function. Using variations in
      hemodynamic concentration signals, R-fNIRS measures the brain's low-frequency
      spontaneous neural activity, combining the advantages of portability, low-cost,
      high temporal sampling rate and less physical burden to participants. The
      temporal synchronization of spontaneous neuronal activity in anatomically
      separated regions is referred to as resting-state functional connectivity (RSFC).
      In the past several years, an increasing body of R-fNIRS RSFC studies has led to
      many important findings about functional integration among local or whole-brain
      regions by measuring inter-regional temporal synchronization. Here, we summarize
      recent advances made in the R-fNIRS RSFC methodologies, from the detection of
      RSFC (e.g., seed-based correlation analysis, independent component analysis,
      whole-brain correlation analysis, and graph-theoretical topological analysis), to
      the assessment of RSFC performance (e.g., reliability, repeatability, and
      validity), to the application of RSFC in studying normal development and brain
      disorders. The literature reviewed here suggests that RSFC analyses based on R
      fNIRS data are valid and reliable for the study of brain function in healthy and
      diseased populations, thus providing a promising imaging tool for cognitive
      science and clinics. 

PMID- 24022324
TI  - Incidence of venous thromboembolism after bariatric surgery: a population-based
      cohort study.
AB  - BACKGROUND: The incidence of venous thromboembolism (VTE) after bariatric surgery
      is uncertain. METHODS: Using the resources of the Rochester Epidemiology Project
      and the Mayo Bariatric Surgery Registry, we identified all residents of Olmsted
      County, Minnesota, with incident VTE after undergoing bariatric surgery from 1987
      through 2005. Using the dates of bariatric surgery and VTE events, we determined
      the cumulative incidence of VTE after bariatric surgery by using the Kaplan-Meier
      estimator. Cox proportional hazards modeling was used to assess patient age, sex,
      weight, and body mass index as potential predictors of VTE after bariatric
      surgery. RESULTS: We identified 396 residents who underwent 402 bariatric
      operations. The most common operation was an open Roux-en-Y gastric bypass (n
      =228). Eight patients had VTE that developed within 6 months (7 within 1month)
      after surgery; five events occurred after hospital discharge but within 1 month
      after bariatric surgery. The cumulative incidence of VTE at 7, 30, 90, and 180
      days was 0.3, 1.9, 2.1, and 2.1%, respectively (180-day 95% confidence interval
      (CI), 0.7-3.6%). Patient age was a predictor of postoperative VTE (hazard ratio,
      1.89 per 10-year increase in age; 95% CI, 1.01-3.55; P=0.05). CONCLUSIONS: In our
      population-based study, bariatric surgery had a high risk of VTE, especially for
      older patients. Because most VTE events occurred after hospital discharge, a
      randomized controlled trial of extended outpatient thromboprophylaxis is
      warranted in patients undergoing open Roux-en-Y gastric bypass for medically
      complicated obesity.

PMID- 24022326
TI  - Detection of architectural distortion in prior mammograms via analysis of
      oriented patterns.
AB  - We demonstrate methods for the detection of architectural distortion in prior
      mammograms of interval-cancer cases based on analysis of the orientation of
      breast tissue patterns in mammograms. We hypothesize that architectural
      distortion modifies the normal orientation of breast tissue patterns in
      mammographic images before the formation of masses or tumors. In the initial
      steps of our methods, the oriented structures in a given mammogram are analyzed
      using Gabor filters and phase portraits to detect node-like sites of radiating or
      intersecting tissue patterns. Each detected site is then characterized using the
      node value, fractal dimension, and a measure of angular dispersion specifically
      designed to represent spiculating patterns associated with architectural
      distortion. Our methods were tested with a database of 106 prior mammograms of 56
      interval-cancer cases and 52 mammograms of 13 normal cases using the features
      developed for the characterization of architectural distortion, pattern
      classification via quadratic discriminant analysis, and validation with the leave
      one-patient out procedure. According to the results of free-response receiver
      operating characteristic analysis, our methods have demonstrated the capability
      to detect architectural distortion in prior mammograms, taken 15 months (on the
      average) before clinical diagnosis of breast cancer, with a sensitivity of 80% at
      about five false positives per patient. 

PMID- 24022327
TI  - Biomechanical imaging of cell stiffness and prestress with subcellular
      resolution.
AB  - Knowledge of cell mechanical properties, such as elastic modulus, is essential to
      understanding the mechanisms by which cells carry out many integrated functions
      in health and disease. Cellular stiffness is regulated by the composition,
      structural organization, and indigenous mechanical stress (or prestress) borne by
      the cytoskeleton. Current methods for measuring stiffness and cytoskeletal
      prestress of living cells necessitate either limited spatial resolution but with
      high speed, or spatial maps of the entire cell at the expense of long imaging
      times. We have developed a novel technique, called biomechanical imaging, for
      generating maps of both cellular stiffness and prestress that requires less than
      30 s of interrogation time, but which provides subcellular spatial resolution.
      The technique is based on the ability to measure tractions applied to the cell
      while simultaneously observing cell deformation, combined with capability to
      solve an elastic inverse problem to find cell stiffness and prestress
      distributions. We demonstrated the application of this technique by carrying out
      detailed mapping of the shear modulus and cytoskeletal prestress distributions of
      3T3 fibroblasts, making no assumptions regarding those distributions or the
      correlation between them. We also showed that on the whole cell level, the
      average shear modulus is closely associated with the average prestress, which is
      consistent with the data from the literature. Data collection is a
      straightforward procedure that lends itself to other biochemical/biomechanical
      interventions. Biomechanical imaging thus offers a new tool that can be used in
      studies of cell biomechanics and mechanobiology where fast imaging of cell
      properties and prestress is desired at subcellular resolution.

PMID- 24022328
TI  - Reply: To PMID 23860661.

PMID- 24022330
TI  - Does neutrophil gelatinase-asociated lipocalin have prognostic value in patients
      with stable angina undergoing elective PCI? A 3-year follow-up study.
AB  - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), a widely accepted
      diagnostic marker of acute renal injury (AKI) may be involved in the development
      of atherosclerosis. PURPOSE: To assess the prognostic significance of serum and
      urinary NGAL and serum cystatin C in patients with stable angina undergoing
      percutaneous coronary intervention (PCI) on a 3-year follow-up. METHODS: We
      included patients with stable angina undergoing PCI. Serum NGAL and cystatin C
      were evaluated before and 4h, 8h after PCI. Urinary NGAL was evaluated before and
      12h and 24h after the procedure. The primary end-point was all-cause mortality on
      a 3-year follow-up. RESULTS: Among 132 patients there were 63% of males (mean age
      64,5+/-9,8 years). Mean eGFR was 86.2+/-28.5 ml/min. During follow-up 8% of the
      patients died. All-cause mortality was significantly higher in patients with
      increased urinary NGAL concentration 12h after PCI (p=0.04). Urinary NGAL 12h
      after PCI correlated with eGFR (p<0.05), with serum NGAL evaluated before and 4h
      and 8h after PCI (p<0.05) and with increased serum cystatin C evaluated 4 hours
      after PCI (p<0.05). CONCLUSIONS: Increased urinary NGAL concentration is a strong
      predictor of mortality in patients with stable angina who undergo PCI and may be
      used for the risk stratification in this population.

PMID- 24022329
TI  - Osteoclasts on bone and dentin in vitro: mechanism of trail formation and
      comparison of resorption behavior.
AB  - The main function of osteoclasts in vivo is the resorption of bone matrix,
      leaving behind typical resorption traces consisting of pits and trails. The
      mechanism of pit formation is well described, but less is known about trail
      formation. Pit-forming osteoclasts possess round actin rings. In this study we
      show that trail-forming osteoclasts have crescent-shaped actin rings and provide
      a model that describes the detailed mechanism. To generate a trail, the actin
      ring of the resorption organelle attaches with one side outside the existing
      trail margin. The other side of the ring attaches to the wall inside the trail,
      thus sealing that narrow part to be resorbed next (3-21 lm). This 3D
      configuration allows vertical resorption layer-by-layer from the surface to a
      depth in combination with horizontal cell movement. Thus, trails are not just
      traces of a horizontal translation of osteoclasts during resorption.
      Additionally, we compared osteoclastic resorption on bone and dentin since the
      latter is the most frequently used in vitro model and data are extrapolated to
      bone. Histomorphometric analyses revealed a material-dependent effect reflected
      by an 11-fold higher resorption area and a sevenfold higher number of pits per
      square centimeter on dentin compared to bone. An important material-independent
      aspect was reflected by comparable mean pit area (MUm2) and podosome patterns.
      Hence, dentin promotes the generation of resorbing osteoclasts, but once
      resorption has started, it proceeds independently of material properties. Thus,
      dentin is a suitable model substrate for data acquisition as long as osteoclast
      generation is not part of the analyses.

PMID- 24022332
TI  - Linezolid-induced thrombocytopenia in impaired renal function: is it time for a
      dose adjustment? A case report and review of literature.
AB  - PURPOSE: Thrombocytopenia is a common complication in the intensive care unit
      (ICU), but the incidence of drug-induced thrombocytopenia (DIT) is not well
      defined. We investigate linezolid-induced thrombocytopenia in patients with
      impaired renal function. Since recent studies suggest that linezolid clearance is
      reduced in these patients and there are no precise data confirming that dose
      adjustment should be required, we performed a systematic analysis in order to
      establish whether it is necessary to consider a dose adjustment and promote
      studies to confirm this concept. METHODS: We report a case of thrombocytopenia
      (nadir 32 * 10(3)/MUl) in a patient with acute kidney injury who was treated with
      linezolid for a MRSA pulmonary infection. We performed a systematic review of the
      literature through PubMed with the aim to include every case report, case series,
      prospective and retrospective clinical study reporting linezolid-induced
      thrombocytopenia with concomitant impaired renal function. RESULTS: An increasing
      number of clinical studies suggest a correlation between the onset of linezolid
      induced thrombocytopenia and renal dysfunction. Close monitoring of platelet
      count and hemoglobin is recommended in patients treated with linezolid,
      especially in those with impaired renal function because the reduction of its
      clearance causes drug accumulation, as some studies have reported. CONCLUSIONS:
      Clinicians should consider the potential risk of this complication, especially in
      elderly patients with end-stage renal disease. Further studies should be
      encouraged to determine if the incidence of linezolid-related thrombocytopenia
      could be reduced by a dose adjustment according to renal function, for which
      currently there is still no specific recommendation.

PMID- 24022331
TI  - Percutaneous interventional mitral regurgitation treatment using the Mitra-Clip
      system.
AB  - The interventional treatment of mitral valve regurgitation by the MitraClip
      procedure has grown rapidly in Germany and Europe during the past years. The
      MitraClip procedure has the potential to treat high-risk patients with secondary
      mitral valve regurgitation and poor left ventricular function. Furthermore,
      patients with primary mitral valve regurgitation may be treated successfully by
      the MitraClip procedure in case of high surgical risk or in very old patients. At
      the same time it has been emphasised that the MitraClip interventional treatment
      is still at an early stage of clinical development. The largest clinical
      experience with the MitraClip procedure so far is probably present in some German
      cardiovascular centers, which here summarise their recommendations on the current
      indications and procedural steps of the MitraClip treatment. These
      recommendations of the AGIK and ALKK may present a basis for future development.

PMID- 24022334
TI  - Next-Generation Anchor Based Phylogeny (NexABP): constructing phylogeny from next
      generation sequencing data.
AB  - Whole genome sequences are ideally suited for deriving evolutionary relationship
      among organisms. With the availability of Next Generation sequencing (NGS)
      datasets in an unprecedented scale, it will be highly desirable if phylogenetic
      analysis can be carried out using short read NGS data. We described here an
      anchor based approach NexABP for phylogenetic construction of closely related
      strains/isolates from NGS data. This approach can be used even in the absence of
      a fully assembled reference genome and works by reducing the complexity of the
      datasets without compromising results. NexABP was used for constructing phylogeny
      of different strains of some of the common pathogens, such as Mycobacterium
      tuberculosis, Vibrio cholera and Escherichia coli. In addition to classification
      into distinct lineages, NexABP could resolve inner branches and also allow
      statistical testing using bootstrap analysis. We believe that there are some
      clear advantages of using NexABP based phylogenetic analysis as compared to other
      methods. 

PMID- 24022333
TI  - Oral rinses, mouthwashes and sprays for improving recovery following
      tonsillectomy.
AB  - BACKGROUND: This is an update of a Cochrane review first published in The
      Cochrane Library in Issue 1, 2010 and previously updated in 2011.Tonsillectomy is
      the surgical removal of lymphoid tissue, the palatine tonsil, which is located at
      the back of the throat. It is still commonly performed for patients who have
      recurrent bouts of acute tonsillitis. Although tonsillectomy is considered a
      fairly minor procedure, pain and bleeding are two of the most common
      complications; either may delay recovery and can on occasion lead to hospital
      readmission. Postoperative tonsillectomy medication should provide an adequate
      reduction in morbidity while minimising side effects, therefore topical agents
      would seem to be an ideal, safe option. A number of mouthwashes and topical
      sprays are available which offer pain relief or can help to reduce bleeding in
      the immediate postoperative period. OBJECTIVES: To assess the effects of oral
      rinses, mouthwashes and sprays in improving recovery following tonsillectomy.
      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 most
      recent search was 4 July 2013. SELECTION CRITERIA: We included randomised
      controlled trials in which oral rinses, mouthwashes and sprays, used pre- and
      postoperatively, have been compared with placebo in adults or children undergoing
      tonsillectomy, with or without adenoidectomy. DATA COLLECTION AND ANALYSIS: Two
      review authors selected trials for inclusion, assessed the risk of bias and
      extracted data independently. MAIN RESULTS: We included seven trials (593
      participants; 397 children and 196 adults). The period of follow-up ranged from
      24 hours to two weeks. Few of the trials provided reliable data for the pre
      specified primary outcomes and none for the secondary outcomes. The risk of bias
      was high in most of the included trials. Lidocaine spray appeared to be more
      effective than saline spray at reducing the severity of pain until the third
      postoperative day. A small number of participants experienced a burning or
      stinging sensation with benzydamine spray but not sufficient to discontinue
      usage. AUTHORS' CONCLUSIONS: Poor reporting quality and inadequate data did not
      permit comprehensive and reliable conclusions to be made. Future trials should be
      well-constructed and pay more attention to the methods used to assess outcomes,
      the timing of the assessments, and the quality of reporting and subsequent
      analysis of the data.

PMID- 24022335
TI  - Tandem decarboxylative hydroformylation-hydrogenation reaction of alpha,beta
      unsaturated carboxylic acids toward aliphatic alcohols under mild conditions
      employing a supramolecular catalyst system.
AB  - A new atom economic catalytic method for a highly chemoselective reduction of
      alpha,beta-unsaturated carboxylic acids to the corresponding saturated alcohols
      under mild reaction conditions, compatible with a wide range reactive functional
      groups, is reported. The new methodology consists of a novel tandem
      decarboxylative hydroformylation/aldehyde reduction sequence employing a unique
      supramolecular catalyst system. 

PMID- 24022336
TI  - Carbon nanotubes on a spider silk scaffold.
AB  - Understanding the compatibility between spider silk and conducting materials is
      essential to advance the use of spider silk in electronic applications. Spider
      silk is tough, but becomes soft when exposed to water. Here we report a strong
      affinity of amine-functionalised multi-walled carbon nanotubes for spider silk,
      with coating assisted by a water and mechanical shear method. The nanotubes
      adhere uniformly and bond to the silk fibre surface to produce tough, custom
      shaped, flexible and electrically conducting fibres after drying and contraction.
      The conductivity of coated silk fibres is reversibly sensitive to strain and
      humidity, leading to proof-of-concept sensor and actuator demonstrations. 

PMID- 24022338
TI  - Electronic excited states and electronic spectra of biphenyl: a study using many
      body wavefunction methods and density functional theories.
AB  - The low-lying electronic excited states of biphenyl were studied using the
      symmetry-adapted cluster-configuration interaction (SAC-CI), complete active
      space self-consistent field (CASSCF), complete active space perturbation theory
      of the second-order (CASPT2), and the time-dependent density functional theory
      (TDDFT). The molecular geometries in the ground and excited states were optimized
      using the SAC-CI and TDDFT for singlet and triplet states. The energies of
      vertical excitations, emissions, and adiabatic transitions were calculated. The
      TDDFT calculations significantly underestimated the excitation energy of the
      1(1)B1 state, while the SAC-CI and CASPT2 provided essentially similar results.
      The present SAC-CI and CASPT2 calculations concluded that the lowest singlet
      state of isolated biphenyl is the 1(1)B3 state that takes a planar geometry and
      the second lowest state is the 1(1)B2 state with a twisted geometry. The present
      results were consistent with the previous experimental findings. The 1(1)B1 state
      that has a charge-separated biracial character in the vertical excitation relaxed
      into a planar quinoid structure in which bond alternations were emphasized. The
      other states took a benzenoid structure. The ultraviolet (UV) absorption and
      circular dichroism (CD) spectra below 7 eV were calculated with the SAC-CI
      method. The valence-Rydberg mixings were found to be significant in the second
      and higher series of excited states. 

PMID- 24022337
TI  - The evolution of personality in patients with mild cognitive impairment.
AB  - AIMS: To describe personality traits and their changes in mild cognitive
      impairment (MCI) and control subjects. METHODS: Sixty-three MCI and 90 control
      subjects were asked to describe their current personality traits by the
      Structured Interview for the Five-Factor Model (SIFFM). For each subject, a close
      relative retrospectively assessed these descriptions both as to the previous and
      current personality traits, using the Revised NEO Personality Inventory, Form R
      (NEO-PI-R). RESULTS: Self-assessed MCI subjects reported significantly lower
      scores in the openness dimension than control subjects [F(1, 150) = 9.84, p =
      0.002, etap(2) = 0.06]. In current observer ratings, MCI subjects had higher
      scores on neuroticism [F(1, 137) = 7.55, p = 0.007, etap(2) = 0.05] and lower
      ones on extraversion [F(1, 137) = 6.40, p = 0.013, etap(2) = 0.04], openness
      [F(1, 137) = 9.93, p = 0.002, etap(2) = 0.07], agreeableness [F(1, 137) = 10.18,
      p = 0.002, etap(2) = 0.07] and conscientiousness [F(1, 137) = 25.96, p < 0.001,
      etap(2) = 0.16]. Previous personality traits discriminated the groups as previous
      openness [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, p =
      0.014] and conscientiousness (OR = 0.96, 95% CI 0.94-0.98, p = 0.001) were
      negatively related to MCI group membership. In MCI subjects, conscientiousness
      [F(1, 137) = 19.20, p < 0.001, etap(2) = 0.12] and extraversion [F(1, 137) =
      22.27, p < 0.001, etap(2) = 0.14] decreased between previous and current
      evaluations and neuroticism increased [F(1, 137) = 22.23, p < 0.001, etap(2) =
      0.14], whereas no significant change was found in control subjects. CONCLUSIONS:
      MCI subjects undergo significant personality changes. Thus, personality
      assessment may aid the early detection of dementia.

PMID- 24022339
TI  - Hydrogen bonded polymeric multilayer films assembled below and above the cloud
      point temperature.
AB  - Polymeric multilayer films assembled via hydrogen-bonding are witnessing
      increased interest from the scientific community. Here we report on hydrogen
      bonded multilayers of tannic acid and neutral poly(2-oxazoline)s. Importantly we
      demonstrate, to the best of our knowledge, for the first time that a temperature
      responsive polymer, in this case poly(2-(n-propyl)-2-oxazline), can be assembled
      below and above its TCP with distinctly different growth mechanisms. 

PMID- 24022340
TI  - Induction and analysis of epithelial to mesenchymal transition.
AB  - Epithelial to mesenchymal transition (EMT) is essential for proper morphogenesis
      during development. Misregulation of this process has been implicated as a key
      event in fibrosis and the progression of carcinomas to a metastatic state.
      Understanding the processes that underlie EMT is imperative for the early
      diagnosis and clinical control of these disease states. Reliable induction of EMT
      in vitro is a useful tool for drug discovery as well as to identify common gene
      expression signatures for diagnostic purposes. Here we demonstrate a
      straightforward method for the induction of EMT in a variety of cell types.
      Methods for the analysis of cells pre- and post-EMT induction by
      immunocytochemistry are also included. Additionally, we demonstrate the
      effectiveness of this method through antibody-based array analysis and
      migration/invasion assays. 

PMID- 24022341
TI  - Epithelial cell turnover is increased in the excluded stomach mucosa after Roux
      en-Y gastric bypass for morbid obesity.
AB  - BACKGROUND: Mucosal alterations after Roux-en-Y gastric bypass for morbid obesity
      have not been clearly evaluated. This study aims to analyze the mucosal
      alterations (proliferative status (Ki-67); apoptosis (caspase-3 and BCL-2);
      hormonal function (gastrin)) in the excluded stomach. METHODS: Double-balloon
      enteroscopy was performed in 35 patients who underwent Roux-en-Y gastric bypass
      longer than 36 months. Multiple biopsies of the proximal pouch and the excluded
      gastric mucosa were collected. Gastric biopsies from 32 non-operated obese
      patients were utilized as controls. Endoscopic biopsies were cut from tissue
      blocks fixed in formalin and embedded in paraffin. Sections 4 MUm thick were
      examined for immunoexpression using the streptavidin-biotin-peroxidase method.
      RESULTS: The two groups were comparable for age, gender, gastritis, intestinal
      metaplasia, and Helicobacter pylori. The mean number of positive gastrin cells
      was 55.5 (standard deviation (SD) = 11.7) in the control group and 29.6 (SD =
      7.9) in the cases, p = 0.0003. Ki-67 proliferative index in cases (body = 24.7%,
      antrum = 24.9%) was significantly higher compared to controls (body = 15.0% and
      antrum = 17.7%), p = 0.002 and 0.01, respectively. Caspase-3 immunoexpression was
      higher in the controls compared to the excluded stomach (46 vs. 31%), p = 0.02.
      There was no statistical difference between CD3, CD8, and Bcl-2 immunoexpressions
      in the control and cases. CONCLUSIONS: Cell proliferation is increased and
      apoptosis is downregulated in the excluded gastric mucosa compared to the non
      operated obese controls. Alterations in cell turnover and in hormonal secretions
      in these conditions may be of relevance in long-term follow-up.

PMID- 24022342
TI  - MiR-199a suppresses the hypoxia-induced proliferation of non-small cell lung
      cancer cells through targeting HIF1alpha.
AB  - Deregulated microRNAs (miRNAs) are small noncoding RNAs that are involved in the
      carcinogenesis of various cancers, including lung cancer. HIF1a has been
      suggested to be a master regulator of hypoxia-induced cell proliferation. The
      relationship between HIF1a expression and the progression of non-small cell lung
      cancer (NSCLC) is not fully understood, and whether HIF1a expression is regulated
      by miRNAs in this process remains unclear. In this study, we found that the
      upregulation of HIF1a expression and the reduction in miR-199a levels were highly
      associated with NSCLC progression. NSCLC cells derived from cancer tissues with
      low miR-199a levels showed high HIF1a expression and high proliferation capacity.
      Moreover, HIF1a and glycolysis inhibitors suppress the proliferation of NSCLC
      cells. MiR-199a overexpression suppressed the hypoxia-induced proliferation of
      NSCLC cells through targeting elevated HIF1a and blocking the downstream
      upregulation of PDK1 without affecting AKT activation. Together, these results
      indicate that downregulation of miR-199a is essential for hypoxia-induced
      proliferation through derepressing the expression of HIF1a expression and
      affecting HIF1a mediated glycolytic pathway in NSCLC progression.

PMID- 24022344
TI  - Clinicopathologic characteristics of pancreatic neuroendocrine tumors and
      relation of somatostatin receptor type 2A to outcomes.
AB  - BACKGROUND: The impact of somatostatin receptor type 2 (SSTR-2a) expression
      levels on outcomes in patients with pancreatic neuroendocrine tumors (PNETs) has
      not been evaluated. METHODS: Correlations between clinicopathologic
      characteristics, including SSTR-2a expression and outcomes, were retrospectively
      studied in 79 patients with pancreatic neuroendocrine tumors (PNETs). RESULTS:
      The SSTR-2a score was 0 in 27% of patients, 1 in 24% of patients, 3 in 30% of
      patients, and 4 in 18% of patients. The overall survival rate was 87% at 1 year,
      77% at 3 years, and 71% at 5 years. On univariate analysis, a pancreatic tumor
      that measured >= 20 mm in greatest dimension, stage IV disease, vascular
      invasion, neuroendocrine carcinoma (NEC), and an SSTR-2a score of 0 were
      associated significantly with poor outcomes. On multivariate analysis, NEC (P =
      .000; hazard ratio, 28.8; 95% confidence interval, 7.502-111.240) and an SSTR-2a
      score of 0 (P = .001; hazard ratio, 3.611; 95% confidence interval, 1.344-9.702)
      were related independently to poor outcomes. CONCLUSIONS: The current analysis of
      prognostic factors in patients with PNETs demonstrated that NEC and an SSTR-2a
      score of 0 both were significant independent predictors of poor outcomes. The
      results suggest that the assessment of SSTR-2a may facilitate the selection of
      treatment regimens and the prediction of outcomes. Because a considerable
      proportion of patients with NEC have SSTR-2a-positive tumors, further analyses of
      the usefulness of somatostatin analogues are warranted in patients who have SSTR
      2a-positive NEC.

PMID- 24022343
TI  - Ethanol and age enhances fluoride toxicity through oxidative stress and
      mitochondrial dysfunctions in rat intestine.
AB  - Fluoride toxicity and alcohol abuse are the two serious public health problems in
      many parts of the world. The current study was an attempt to investigate the
      effect of alcohol administration and age on fluoride toxicity in rat intestine.
      Six and 18 months old female Sprague Dawley rats were exposed to sodium fluoride
      (NaF, 25 mg/kg), 30 % ethanol (EtOH, 1 ml/kg), and NaF+EtOH (25 mg/kg+1 ml/kg)
      for a period of 20, 40, and 90 days. The levels of lipid peroxidation were
      increased, while the content of reduced glutathione, total, and protein thiol was
      decreased with NaF treatment. Under these conditions, animals showed an age
      related decline in the activities of superoxide dismutase, catalase, glutathione
      peroxidase, glutathione reductase, and glutathione-S-transferase which were
      further aggravated upon NaF or/and EtOH treatment. Mitochondrial respiration rate
      and the activities of complexes I, II, and IV enzymes of electron transport chain
      were decreased, while the levels of nitric oxide and citrulline were increased
      with age and NaF or/and EtOH treatment. Histological examination revealed large
      reactive lymphoid follicles, excess of lymphocytes in lamina propria of villi,
      villous edema, focal ileitis, necrosis of villi, and ulceration in NaF- or/and
      EtOH-treated animals in both the age groups. These findings suggest that fluoride
      mediate its toxic effects on intestine through oxidative stress and mitochondrial
      dysfunctions which are further augmented with alcohol consumption and advancing
      age.

PMID- 24022345
TI  - Development and characterisation of ursolic acid nanocrystals without stabiliser
      having improved dissolution rate and in vitro anticancer activity.
AB  - Ursolic acid (UA), which is a natural pentacyclic triterpenoid, has the potential
      to be developed as an anticancer drug, whereas its poor aqueous solubility and
      dissolution rate limit its clinical application. The aim of the present study was
      to develop UA nanocrystals to enhance its aqueous dispersibility, dissolution
      rate and anticancer activity. Following the investigation on the effects of
      stabiliser, the ratio of organic phase to aqueous solution and drug
      concentration, the UA nanocrystals without stabiliser were successfully prepared
      by anti-solvent precipitation approach. The nanocrystals maintained similar
      crystallinity with particle size, polydispersion index and zeta potential values
      of 188.0 +/- 4.4 nm, 0.154 +/- 0.022, and -25.0 +/- 5.9 mV, respectively.
      Compared with the raw material, the UA nanocrystals showed good aqueous
      dispensability and a higher dissolution rate, and they could be completely
      dissolved in 0.5% SDS solution within 120 min. Moreover, the suspension of UA
      nanocrystals was physically stable after storage at 4 degrees C for 7 weeks. By
      inducing G2/M phase cell cycle arrest, the UA nanocrystals significantly induced
      stronger cell growth inhibition activity against MCF-7 cells compared with free
      drug in vitro, although the uptake of free UA was approximately twice higher than
      that of the UA nanocrystals. The UA nanocrystals may be used as a potential
      delivery formulation for intravenous injection with enhanced dissolution velocity
      and anticancer activity.

PMID- 24022346
TI  - Use of preclinical dog studies and absorption modeling to facilitate late stage
      formulation bridging for a BCS II drug candidate.
AB  - Formulation changes are common during drug development either due to clinical or
      manufacturing considerations. These changes especially at later stages of drug
      development oftentimes raise questions on the potential impact of a new
      formulation on bioavailability. In this work, the preclinical assessment of
      formulation bridging risk for a Biopharmaceutics Classification System II
      development compound is presented. Early clinical studies were conducted using a
      liquid-filled capsule (LFC). To assess the feasibility of a conventional solid
      dosage form, an initial analysis was conducted using absorption modeling which
      indicated conventional formulation of micronized active pharmaceutical ingredient
      (API) could be a viable option. Subsequently, test formulations were prepared and
      tested in vivo in dogs. The solid formulations were able to match exposures of
      the LFC capsule in the dog model; in addition, a sensitivity to API PSD was
      observed in line with the modeling predictions. When tested in the clinic, the
      conventional solid formulation resulted in exposures of approximately 25% lower
      compared to the LFC on an equivalent dose basis; however, bridging with a small
      dose adjustment would be feasible. The outcome of the clinical study was better
      predicted by the modeling approach while the dog model appeared to somewhat
      overestimate absorption. Through the use of preclinical tools and modeling and
      simulation, a risk assessment around formulation bridging can be conducted and
      inform formulation decisions or subsequent clinical study designs.

PMID- 24022347
TI  - Silicone adhesive matrix of verapamil hydrochloride to provide pH-independent
      sustained release.
AB  - Providing pH-independent oral release of weakly basic drugs with conventional
      matrix tablets can be challenging because of the pH-dependent solubility
      characteristics of the drugs and the changing pH environment along the
      gastrointestinal tract. The aim of the present study was to use a hydrophobic
      polymer to overcome the issue of pH-dependent release of weakly basic model drug
      verapamil hydrochloride from matrix tablets without the use of organic buffers in
      the matrix formulations. Silicone pressure-sensitive adhesive (PSA) polymer was
      evaluated because of its unique properties of low surface energy, hydrophobicity,
      low glass transition temperature, high electrical resistance, and barrier to
      hydrogen ion diffusion. Drug release, hydrogen ion diffusion, tablet contact
      angle, and internal tablet microenvironment pH with matrix tablets prepared using
      PSA were compared with those using water-insoluble ethyl cellulose (EC). Silicone
      PSA films showed higher resistance to hydrogen ion diffusion compared with EC
      films. Verapamil hydrochloride tablets prepared using silicone PSA showed higher
      hydrophobicity and lower water uptake than EC tablets. Silicone PSA tablets also
      showed pH-independent release of verapamil and decreased in dimensions during
      drug dissolution. By contrast, verapamil hydrochloride tablets prepared using EC
      did not achieve pH-independent release.

PMID- 24022348
TI  - Institutional Review Boards, declaration of Helsinki, and HIPAA regulations.

PMID- 24022349
TI  - The meaning of diagnoses in orbital disease.

PMID- 24022350
TI  - Orbital pseudotumor versus idiopathic nongranulomatous orbital inflammation.

PMID- 24022351
TI  - Use of x-ray film implant for the repair of orbital fractures.
AB  - PURPOSE: To evaluate the experience with sterilized x-ray film in the repair of
      orbital blow-out fractures (BOFs). METHODS: A retrospective review of case notes
      from 56 patients with orbital BOF repaired using sterilized x-ray film onlay
      implants at 2 institutions between November 2004 and December 2010. Patient
      demographics, timing of surgery, surgical approach, postoperative complications,
      and length of follow up were recorded. RESULTS: Fifty-six patients (44 men, 12
      women) received sterilized x-ray film implants during the 6-year study period.
      Mean age at the time of repair was 29 years (range 4-85 years). For 68% of
      patients, surgical repair was performed within 2 weeks of injury. Average length
      of postoperative follow up was 5.5 months (range 1-36 months), 48% had follow up
      >3 months. Following surgical repair, diplopia in primary or down gaze reduced
      from 98% to 4% and enophthalmos >=2 mm reduced from 21% to 5% cases. One patient
      required a second operation for repositioning of an incompletely reduced
      fracture. A second patient presented 9 months postoperatively with recurrent
      episodes of proptosis, and the implant and its surrounding pseudocapsule were
      subsequently removed. There were no cases of visual loss, implant infection, or
      migration. CONCLUSIONS: This series has demonstrated that in selected orbital
      fractures sterilized x-ray film can provide a safe, effective, and low-cost onlay
      implant.

PMID- 24022352
TI  - Acute, unilateral transient blepharoptosis of unknown etiology: a review.
AB  - PURPOSE: To describe 5 patients with transient, acute, unilateral blepharoptosis
      of unknown etiology. METHODS: Medical records of 5 patients, which were seen in 5
      different clinics between 1998 and 2011, were reviewed. RESULTS: The ages of the
      patients were 7, 7, 32, 44, and 75 years (2 women and 3 men). Four patients had
      partial (1.5-3.5 mm) and 1 patient had total ptosis. Levator function was normal
      in 2 patients, and 3 patients had only 2 to 3 mm decreased levator function on
      the affected side. None of the patients had limited motility or any pupil
      abnormalities. All patients had a history of flu-like illness preceding the
      development of blepharoptosis. The ptosis completely resolved in 3 to 14 days in
      all patients and did not recur during the follow-up period (range: 2 months-7
      years). CONCLUSIONS: Transient, acute, unilateral blepharoptosis is a very rare
      condition. Patients presenting with acute ptosis should be questioned about a
      recent history of flu-like syndrome, and if workup is negative with this history,
      the clinicians should suspect this rare condition.

PMID- 24022353
TI  - Inverting sutures for tarsal ectropion (the leicester modified suture technique).
AB  - PURPOSE: To describe a simple technique to correct tarsal lower eyelid ectropion
      with or without marked eyelid laxity (The Leicester Modified Suture technique).
      METHODS: A retrospective interventional case series of patients undergoing
      correction of tarsal ectropion with inverting sutures. The study adhered to the
      principles of the Declaration of Helsinki. RESULTS: Twenty patients (25 eyelids)
      met the inclusion criteria. The success of the procedure was assessed by
      improvement of symptoms, eyelid position, and the need for reoperation. The mean
      postoperative follow up was 3.6 months (range 2-15 months). Eighteen patients
      (90%) had a successful outcome, while in 2 patients (10%) the outcome was
      satisfactory, as there was mild residual eversion of the eyelids. None of the
      patients required reoperation. CONCLUSIONS: Tarsal lower eyelid ectropion can be
      surgically challenging to correct via the transconjunctival plication or
      subciliary reattachment of retractors. This method is simple to use, resulting in
      an excellent outcome with no tissue dissection. This technique is easy to learn
      and implement for oculoplastic surgeons at all levels of experience.

PMID- 24022354
TI  - Re: "electronically assisted nasolacrimal duct silicone intubation".

PMID- 24022355
TI  - Reply re: "electronically assisted nasolacrimal duct silicone intubation".

PMID- 24022356
TI  - Re: "an analysis of 2,480 space-occupying lesions of the orbit from 1976 to
      2011".

PMID- 24022357
TI  - Reply re: "an analysis of 2,480 space-occupying lesions of the orbit from 1976 to
      2011".

PMID- 24022358
TI  - Re: "ocular melioidosis".

PMID- 24022359
TI  - Reply re: "ocular melioidosis".

PMID- 24022360
TI  - Management of extruding bicanalicular nasolacrimal stents: Primum non nocere.

PMID- 24022361
TI  - To the editor: the Desmarres does it.

PMID- 24022362
TI  - Solitary fibrous tumor of the orbit with multiple cavities.
AB  - Solitary fibrous tumors (SFTs) are rare spindle cell neoplasms of mesenchymal
      origin that most commonly arise within pleura and have also been reported in many
      extrapleural sites including the orbit. Cavitary changes within SFT of both
      pleura and extrapleural sites have been documented, but remain very rare. To the
      authors' knowledge, the third known case of an orbital solitary fibrous tumor
      containing large pseudocystic cavities is described. MRI demonstrated a
      heterogeneous enhancing mass with multiple cavities. Excisional biopsy revealed
      solid tumor with large cavities filled with straw-colored fluid and tumor cells
      that stained positive for CD34 and CD99 antigens, consistent with SFT. The
      patient had an uncomplicated postoperative course with no sign of recurrence and
      resolution of the proptosis after 12 months of follow up. SFT are rare benign
      orbital neoplasms that rarely present with cavitary changes. Current treatment
      options include complete surgical excision, which was performed in this case.
      Close follow up is advised to monitor for recurrence. 

PMID- 24022363
TI  - Controversial correlation between Fcgamma receptor IIB and Toll-like receptor 2
      in rheumatoid arthritis: comment on the article by Abdollahi-Roodsaz et al.

PMID- 24022364
TI  - Evaluation of Outcomes in Patients With Carcinoma of the Cervix Treated With
      Concurrent Radiation and Cisplatin Versus Cisplatin/5-FU Compared With Radiation
      Alone.
AB  - OBJECTIVES: The objective of this study was to compare outcomes for patients with
      cervical cancer treated with radiation concurrently with cisplatin, cisplatin/5
      fluorouracil (5-FU), or without chemotherapy. MATERIALS AND METHODS: We reviewed
      the records of eligible patients with locoregionally confined, stage IB1 through
      IVA, intact cervical cancer who were treated at Northwestern Memorial Hospital.
      All patients underwent definitive radiotherapy with combined external beam
      radiation-the majority with extended-field (62%)-and received low-dose rate
      brachytherapy. RESULTS: A total of 236 patients were included: 99 had no
      concurrent chemotherapy, 95 were treated with concurrent cisplatin, and 42 were
      treated with cisplatin/5-FU. For all patients treated with or without
      chemotherapy, overall survival at 5 and 10 years was 64% and 59%, respectively.
      Patients treated with chemotherapy had a superior recurrence-free survival rate
      of 69% at 5 years versus 49% in patients who did not receive chemotherapy
      (P=0.09). Twenty-six percent of patients treated with cisplatin alone, 31% of
      patients treated with cisplatin/5-FU, and 45% of patients who did not receive
      chemotherapy experienced a disease recurrence. Adenosquamous histology conferred
      a higher rate of recurrence as compared with adenocarcinoma and squamous cell
      histologies (54% vs. 34%, respectively; P=0.05). CONCLUSIONS: Cisplatin-based
      concurrent chemoradiotherapy showed a trend toward improved recurrence-free
      survival survival in the definitive treatment of nonmetastatic cervical cancer.
      The addition of 5-FU to cisplatin did not appear to significantly impact survival
      or recurrence-free survival. Adenosquamous histology was associated with a higher
      risk of recurrence as compared with other histologic subtypes.

PMID- 24022365
TI  - Why and how we determine nephron number.
AB  - The total number of glomeruli (nephrons) in a kidney is an important
      microanatomical parameter for at least three reasons: it provides an index of the
      success/extent of nephrogenesis and can thereby provide insights into the roles
      of specific genes and feto-maternal environmental factors in nephrogenesis; low
      nephron number has been linked to an increased risk of cardiovascular and renal
      disease in adulthood; and knowledge of quantitative kidney microanatomy can
      illuminate our understanding of physiological mechanisms in health and disease. A
      range of methods has been used to count glomeruli in kidneys over the past 100
      years, with design-based stereology (the physical disector/fractionator
      combination) considered the gold standard. However, this approach is labor
      intensive and expensive, and therefore is not utilized by most laboratories. A
      new method for counting and sizing every glomerulus in the kidney has recently
      been described. This method involves in vivo labeling of glomeruli with cationic
      ferritin, and then magnetic resonance imaging (MRI) of the ex vivo kidney. Values
      are obtained in one sixth of the time of disector-based approaches. This new MRI
      method holds great promise for studies of glomerular number and size ex vivo and
      in vivo.

PMID- 24022366
TI  - To bud or not to bud: the RET perspective in CAKUT.
AB  - Congenital anomalies of the kidneys or lower urinary tract (CAKUT) encompass a
      spectrum of anomalies that result from aberrations in spatio-temporal regulation
      of genetic, epigenetic, environmental, and molecular signals at key stages of
      urinary tract development. The Rearranged in Transfection (RET) tyrosine kinase
      signaling system is a major pathway required for normal development of the
      kidneys, ureters, peripheral and enteric nervous systems. In the kidneys, RET is
      activated by interaction with the ligand glial cell line-derived neurotrophic
      factor (GDNF) and coreceptor GFRalpha1. This activated complex regulates a number
      of downstream signaling cascades (PLCgamma, MAPK, and PI3K) that control
      proliferation, migration, renewal, and apoptosis. Disruption of these events is
      thought to underlie diseases arising from aberrant RET signaling. RET mutations
      are found in 5-30 % of CAKUT patients and a number of Ret mouse mutants show a
      spectrum of kidney and lower urinary tract defects reminiscent of CAKUT in
      humans. The remarkable similarities between mouse and human kidney development
      and in defects due to RET mutations has led to using RET signaling as a paradigm
      for determining the fundamental principles in patterning of the upper and lower
      urinary tract and for understanding CAKUT pathogenesis. In this review, we
      provide an overview of studies in vivo that delineate expression and the
      functional importance of RET signaling complex during different stages of
      development of the upper and lower urinary tracts. We discuss how RET signaling
      balances activating and inhibitory signals emanating from its docking tyrosines
      and its interaction with upstream and downstream regulators to precisely modulate
      different aspects of Wolffian duct patterning and branching morphogenesis. We
      outline the diversity of cellular mechanisms regulated by RET, disruption of
      which causes malformations ranging from renal agenesis to multicystic dysplastic
      kidneys in the upper tract and vesicoureteral reflux or ureteropelvic junction
      obstruction in the lower tract.

PMID- 24022367
TI  - Urine neutrophil gelatinase-associated lipocalin to predict acute kidney injury
      in preterm neonates. A pilot study.
AB  - BACKGROUND: The efficacy of urine neutrophil gelatinase-associated lipocalin
      (uNGAL) as an early acute kidney injury (AKI) biomarker in preterm neonates was
      evaluated. METHODS: Thirty-five preterm neonates were prospectively evaluated for
      serum creatinine (sCre)-documented AKI during the first 14 days of life. Urine
      samples were collected daily throughout the study period. Of the neonates
      evaluated, we analyzed 11 who developed AKI (cases) and an equal number of
      neonates without AKI (controls) matched for gestational and postnatal age (case
      control study). uNGAL was measured on the day of AKI occurrence (day 0) and on
      the 2 days preceding the event (day -1 and day -2, respectively) using an enzyme
      linked immunosorbent assay. RESULTS: Cases had significantly higher sCre levels
      than controls on day 0 (1.21 +/- 0.48 vs. 0.83 +/- 0.16 mg/dL, p =0.031) but not
      on days -1 and -2. Similarly, uNGAL levels (ng/mL) were significantly higher in
      cases than in controls only on day 0 (19.1 +/- 3.5 vs. 13.3 +/- 7.3, p=0.017) and
      not on days -1 (18.8 +/- 3.4 vs. 16.3 +/- 5.9, p=0.118) and -2 (19.3 +/- 1.8 vs.
      19.4 +/- 0.8, p =0.979). The receiver operating characteristic curve analysis
      showed no significant ability of uNGAL to predict AKI on days -2 and -1.
      CONCLUSIONS: In this pilot study in preterm neonates, although uNGAL detected
      sCre-based AKI upon its documentation, it failed to predict its development 1-2
      days earlier.

PMID- 24022368
TI  - Tandem hemodialysis and plasma exchange.
AB  - The combination of hemodialysis and plasma exchange as one tandem procedure was
      first described in 1999 by Siami et al. (ASAIO J 45:229-233), but larger
      pediatric case series were not described until 2012. Even in adults, there are
      only limited case series. If performed in sequence, up to 8 h of treatment time
      may be required. With the use of the tandem procedure in stable patients, the
      same procedures can be completed during the same time as a routine hemodialysis,
      which is more convenient for patients and may reduce healthcare costs. Little is
      known about the utilization of the combination of hemodialysis and plasma
      exchange in children. The purpose of this review is to summarize the adult and
      scarce pediatric experience. The results of a survey carried out by the authors
      using the Internet listserver "PedNeph" to obtain an overview of the current
      practice patterns of pediatric nephrologists are also presented. 

PMID- 24022369
TI  - Haematopoietic stem cell niches: new insights inspire new questions.
AB  - Haematopoietic stem cell (HSC) niches provide an environment essential for life
      long HSC function. Intense investigation of HSC niches both feed off and drive
      technology development to increase our capability to assay functionally defined
      cells with high resolution. A major driving force behind the desire to understand
      the basic biology of HSC niches is the clear implications for clinical therapies.
      Here, with particular emphasis on cell type-specific deletion of SCL and CXCL12,
      we focus on unresolved issues on HSC niches, framed around some very recent
      advances and novel discoveries on the extrinsic regulation of HSC maintenance. We
      also provide ideas for possible paths forward, some of which are clearly within
      reach while others will require both novel tools and vision. 

PMID- 24022371
TI  - Kinetics of Hepatitis B virus load during haemodialysis sessions and alpha
      interferon: a prospective study.
AB  - BACKGROUND: It has been reported a slow progression of hepatitis B in patients
      undergoing maintenance dialysis, and a role of dialysis session per se has been
      suggested. The aim of the present study is to evaluate the kinetics of the
      hepatitis B viral load (HBV DNA) in serum during haemodialysis sessions using a
      highly sensitive technique; the role of interferon-alpha in lowering HBV viral
      load in such patients was also investigated. METHODS: HBV DNA was determined in
      24 HBsAg positive patients on maintenance hemodialysis immediately before and
      after a 4-hour hemodialysis session, the same measurements were repeated 48 and
      72 hours later. HBV DNA quantitation was performed by a novel RealTime PCR assay.
      Serum IFN-alpha levels were tested in parallel in a subset of HD sessions (n=40)
      by ELISA. RESULTS: 20 (83%) HBsAg positive patients had detectable HBV DNA in
      serum. Positive status for HBV DNA in serum was not predicted by demographic,
      clinical or biochemical parameters. HBV load decreased in many patients after
      hemodialysis sessions 5.92 log10 IU/mL (95% CI, 5.34 to 6.28 log10 IU/mL) vs.
      4.79 log10 IU/mL (95% CI, 4.23 to 6.15 log10 IU/mL) (P=0.02). A significant
      relationship between mean HBV DNA levels before dialysis and percentage reduction
      of HBV DNA during HD sessions occurred [F-test=5.41, rho (least squares)=0.307].
      Increase of serum IFN-alpha levels was found in a minority (3/40=7%) of HD
      sessions. CONCLUSIONS: Hemodialysis procedure gives reduction of HBV load in
      HBsAg chronic carriers; no relationship with IFN-alpha activity during HD
      sessions was found. The kinetics of HBV viremia in HD procedures could explain
      the low viral load which is typically observed in these patients. Further studies
      to identify the mechanisms responsible for reduction of HBV viremia during HD
      procedures are under way.

PMID- 24022370
TI  - Differential proliferation rates generate patterns of mechanical tension that
      orient tissue growth.
AB  - Orientation of cell divisions is a key mechanism of tissue morphogenesis. In the
      growing Drosophila wing imaginal disc epithelium, most of the cell divisions in
      the central wing pouch are oriented along the proximal-distal (P-D) axis by the
      Dachsous-Fat-Dachs planar polarity pathway. However, cells at the periphery of
      the wing pouch instead tend to orient their divisions perpendicular to the P-D
      axis despite strong Dachs polarization. Here, we show that these circumferential
      divisions are oriented by circumferential mechanical forces that influence cell
      shapes and thus orient the mitotic spindle. We propose that this circumferential
      pattern of force is not generated locally by polarized constriction of individual
      epithelial cells. Instead, these forces emerge as a global tension pattern that
      appears to originate from differential rates of cell proliferation within the
      wing pouch. Accordingly, we show that localized overgrowth is sufficient to
      induce neighbouring cell stretching and reorientation of cell division. Our
      results suggest that patterned rates of cell proliferation can influence tissue
      mechanics and thus determine the orientation of cell divisions and tissue shape. 

PMID- 24022372
TI  - Myocardial infarction and coronary microvascular obstruction: an intimate, but
      complicated relationship.

PMID- 24022373
TI  - Postconditioning attenuates no-reflow in STEMI patients.
AB  - After acute myocardial infarction, the presence of no-reflow (or microvascular
      obstruction: MVO) has been associated with adverse left ventricular (LV)
      remodeling and worse clinical outcome. This study examined the effects of
      mechanical ischemic postconditioning on early and late MVO size in acute ST
      elevation myocardial infarction (STEMI) patients. Fifty patients undergoing
      primary coronary angioplasty for a first STEMI with TIMI grade flow 0-1 and no
      collaterals were randomized to ischemic postconditioning (PC) (n = 25) or control
      (n = 25) groups. Ischemic PC consisted in the application of four consecutive
      cycles of a 1-min balloon occlusion, each followed by a 1-min deflation at the
      onset of reperfusion. Early (3 min post-contrast) and late (10 min post-contrast)
      MVO size were assessed by contrast-enhanced cardiac-MRI within 96 h after
      reperfusion. PC was associated with smaller early and late MVO size (3.9 +/- 4.8
      in PC versus 7.8 +/- 6.6% of LV in controls for early MVO, P = 0.02; and 1.8 +/-
      3.1 in PC versus 4.1 +/- 3.9% of LV in controls for late MVO; P = 0.01). This
      significant reduction was persistent after adjustment for thrombus aspiration,
      which neither had any significant effect on infarct size, nor on early or late
      MVO (P = NS for all). Attenuation of MVO was associated to infarct size
      reduction. Mechanical postconditioning significantly reduces MVO in patients with
      acute STEMI treated with primary angioplasty.

PMID- 24022374
TI  - Visualizing influenza virus infection in living mice.
AB  - Preventing and treating influenza virus infection remain a challenge because of
      incomplete understanding of the host-pathogen interactions, limited therapeutics
      and lack of a universal vaccine. So far, methods for monitoring the course of
      infection with influenza virus in real time in living animals are lacking. Here
      we report the visualization of influenza viral infection in living mice using an
      engineered replication-competent influenza A virus carrying luciferase reporter
      gene. After intranasal inoculation, bioluminescence can be detected in the chest
      and nasopharyngeal passage of living mice. The intensity of bioluminescence in
      the chest correlates with the dosage of infection and the viral load in the lung.
      Bioluminescence in the chest of infected mice diminishes on antiviral treatment.
      This work provides a novel approach that enables real-time study of influenza
      virus infection and effects of antiviral therapeutics in living animals. 

PMID- 24022376
TI  - The 42nd Annual Meeting of The Japanese Society of Neuroradiology, 15-16 February
      2013, Kokura, Japan.

PMID- 24022375
TI  - The effect of person-centred dementia care to prevent agitation and other
      neuropsychiatric symptoms and enhance quality of life in nursing home patients: a
      10-month randomized controlled trial.
AB  - AIMS: We examined whether Dementia Care Mapping (DCM) or the VIPS practice model
      (VPM) is more effective than education of the nursing home staff about dementia
      (control group) in reducing agitation and other neuropsychiatric symptoms as well
      as in enhancing the quality of life among nursing home patients. METHODS: A 10
      month three-armed cluster-randomized controlled trial compared DCM and VPM with
      control. Of 624 nursing home patients with dementia, 446 completed follow-up
      assessments. The primary outcome was the change on the Brief Agitation Rating
      Scale (BARS). Secondary outcomes were changes on the 10-item version of the
      Neuropsychiatric Inventory Questionnaire (NPI-Q), the Cornell Scale for
      Depression in Dementia (CSDD) and the Quality of Life in Late-Stage Dementia
      (QUALID) scale. RESULTS: Changes in the BARS score did not differ significantly
      between the DCM and the control group or between the VPM and the control group
      after 10 months. Positive differences were found for changes in the secondary
      outcomes: the NPI-Q sum score as well as the subscales NPI-Q agitation and NPI-Q
      psychosis were in favour of both interventions versus control, the QUALID score
      was in favour of DCM versus control and the CSDD score was in favour of VPM
      versus control. CONCLUSIONS: This study failed to find a significant effect of
      both interventions on the primary outcome. Positive effects on the secondary
      outcomes indicate that the methods merit further investigation.

PMID- 24022377
TI  - Influence of neonatal practice variation on outcomes of late preterm birth.
AB  - OBJECTIVE: Examine variation in short-term outcomes of late preterm births
      (34(0/7)-36(6/7) weeks) between a university teaching hospital, teaching
      community hospital, and nonteaching community hospital. STUDY DESIGN: Review of
      maternal and newborn data from a random sample of late preterm births at three
      hospitals in North Carolina from 2008 to 2009. Outcomes included length of stay,
      neonatal intensive care unit (NICU) admission, respiratory support, antibiotic
      exposure, phototherapy exposure, and hypoglycemia. RESULTS: We analyzed data from
      331 singleton late preterm newborns: 93 (28.1%) from a university teaching
      hospital, 110 (33.2%) from a teaching community hospital, and 128 (38.7%) from a
      nonteaching community hospital. Mean gestational age did not vary between
      hospitals. NICU admission, exposure to antibiotics, and phototherapy were more
      common at the university teaching hospital after controlling for risk factors,
      yet length of stay was shortest at the university teaching hospital and longest
      at the teaching community hospital after adjustment. CONCLUSION: Practice
      variation contributes to differences in length of stay, NICU admission, and
      exposure to antibiotics and phototherapy among late preterm newborns. Differences
      in practice during the birth hospitalization may affect outcomes and health care
      utilization (e.g., readmission) after discharge.

PMID- 24022378
TI  - Palivizumab prophylaxis: does it have any influence on the growth and development
      of the infants?
AB  - AIM: To evaluate the rehospitalization rates of premature infants who received
      palivizumab prophylaxis and its influence on the growth and development of these
      infants. METHODS: Infants with a gestational age of less than 32 weeks were
      randomized to receive prophylaxis with palivizumab (study group) or nothing
      (control group). Nasal swab samples were obtained monthly in all cases and also
      in case of infection and hospitalization. At the corrected age of 18 months Guide
      for Monitoring Child Development (GMCD) was administered to all patients and
      anthropometric indices were evaluated. RESULTS: The study was completed with 39
      infants in the study group and 40 infants in the control group. Incidence of
      hospitalization due to respiratory syncitial virus (RSV) was found to be
      significantly lower in the study group both at the year of prophylaxis and in the
      following year (p = 0.001, odds ratio 1.32 [1.11-1.57]). There were no
      significant differences in terms of anthropometric indices or GMCD tests between
      the groups at the corrected age of 18 months. CONCLUSION: Palivizumab reduced the
      incidence of lower respiratory tract infections and hospitalizations due to RSV
      both in the year of prophylaxis and in the following year. However, this decrease
      did not have any impact on the development of infants.

PMID- 24022379
TI  - Is midtrimester vitamin D status associated with spontaneous preterm birth and
      preeclampsia?
AB  - OBJECTIVE: The objective of this study is to evaluate whether midtrimester
      maternal vitamin D is associated with preeclampsia < 37 weeks or spontaneous
      preterm birth (SPTB) < 35 weeks. STUDY DESIGN: Nested case-control comprising two
      case subsets: (1) 100 women with preeclampsia < 37 weeks and (2) 100 women with
      SPB < 35 weeks. Controls consisted of 200 women delivered between 39 and 40
      weeks. Stored maternal serum obtained between 15 and 21 weeks was tested for
      total 25-hydroxy vitamin D (25-OH D) levels using liquid chromatography-tandem
      mass spectrometry. Mean 25-OH D levels and prevalence of vitamin D insufficiency
      (25-OH D < 30 ng/mL) and deficiency (25-OH D < 15 ng/mL) were compared. RESULTS:
      In this study, 89 preeclampsia, 90 SPTB cases, and 177 controls had valid
      measurements. Mean midtrimester vitamin D was not significantly different between
      women with preeclampsia (27.4 ng/mL +/- 14.4) and controls (28.6 +/- 12.6) (p =
      0.46), or SPTB (28.8 +/- 13.2) and controls (p = 0.92). After adjusting for
      potential cofounders, neither vitamin D insufficiency (adjusted odds ratio [OR],
      1.1; 95% confidence interval [CI], 0.6-2.0) nor deficiency (adjusted OR, 1.4; 95%
      CI, 0.7-3.0) was significantly associated with preeclampsia. Likewise, SPTB was
      not significantly associated with either vitamin D insufficiency or deficiency
      (adjusted OR, 0.8; 95% CI, 0.4-1.4, adjusted OR, 1.3 or 95% CI, 0.6-3.0,
      respectively). CONCLUSION: Midtrimester maternal vitamin D was not significantly
      associated with preeclampsia < 37 weeks or SPTB < 35 weeks.

PMID- 24022380
TI  - A supramolecular strategy to assemble multifunctional viral nanoparticles.
AB  - Using a one-pot approach driven by the supramolecular interaction between beta
      cyclodextrin and adamantyl moieties, multifunctional viral nanoparticles can be
      facilely formulated for biomedical applications. 

PMID- 24022381
TI  - Reversible photochromism of an N-salicylidene aniline anion.
AB  - The first N-salicylidene aniline anion showing reversible solid state
      thermochromic and photochromic properties is described. The photo-isomerization
      involves a trans-keto form which is stabilized thanks to the local anion
      surrounding. This photochromic anion can be used as a guest for the preparation
      of hybrid materials by insertion into a cationic host matrix. 

PMID- 24022382
TI  - To the pore and through the pore: thermodynamics and kinetics of helium in exotic
      cubic carbon polymorphs.
AB  - Applying pore size analysis, Monte Carlo simulations, and transition state
      theory, we study the molecular sieving properties of recently discovered
      crystalline exotic cubic carbon allotropes (Hu et al., J. Phys. Chem. C, 2012,
      116, 24233-24238) at 298 K and infinite dilution. The fcc-C10 cubic carbon
      crystal shows unusual molecular sieving characteristics. The carbon cavities of
      the fcc-C10 cubic carbon polymorph (with an effective size of ~3.5-4 A) are
      kinetically closed to common gaseous contaminants of He fluid (including: Ne, Ar,
      H2, and CO). Because the sizes of nanowindows connecting carbon cavities are
      comparable with the effective size of a He atom (~2.556 A), we predict a
      significant resistance to self-diffusion of the He in the fcc-C10 crystal.
      Computed self-diffusion coefficients ~1.3 * 10(-6)-1.3 * 10(-7) cm(2) s(-1) for
      He inside fcc-C10 fall in the range characteristic of molecular diffusion in
      zeolites. Infrequent "jumps" of He atoms between neighboring carbon cavities and
      kinetic rejection of other gaseous particles indicate potential application of
      the fcc-C10 carbon polymorph for kinetic molecular sieving of He near ambient
      temperatures. The theoretical results presented here are useful for correct
      interpretation of the pore volumes of carbon molecular sieves measured from
      helium porosimetry.

PMID- 24022383
TI  - TreeParser-aided Klee diagrams display taxonomic clusters in DNA barcode and
      nuclear gene datasets.
AB  - Indicator vector analysis of a nucleotide sequence alignment generates a compact
      heat map, called a Klee diagram, with potential insight into clustering patterns
      in evolution. However, so far this approach has examined only mitochondrial
      cytochrome c oxidase I (COI) DNA barcode sequences. To further explore, we
      developed TreeParser, a freely-available web-based program that sorts a sequence
      alignment according to a phylogenetic tree generated from the dataset. We applied
      TreeParser to nuclear gene and COI barcode alignments from birds and butterflies.
      Distinct blocks in the resulting Klee diagrams corresponded to species and higher
      level taxonomic divisions in both groups, and this enabled graphic comparison of
      phylogenetic information in nuclear and mitochondrial genes. Our results
      demonstrate TreeParser-aided Klee diagrams objectively display taxonomic clusters
      in nucleotide sequence alignments. This approach may help establish taxonomy in
      poorly studied groups and investigate higher-level clustering which appears
      widespread but not well understood. 

PMID- 24022384
TI  - Protocols for assessing radiofrequency interactions with gold nanoparticles and
      biological systems for non-invasive hyperthermia cancer therapy.
AB  - Cancer therapies which are less toxic and invasive than their existing
      counterparts are highly desirable. The use of RF electric-fields that penetrate
      deep into the body, causing minimal toxicity, are currently being studied as a
      viable means of non-invasive cancer therapy. It is envisioned that the
      interactions of RF energy with internalized nanoparticles (NPs) can liberate heat
      which can then cause overheating (hyperthermia) of the cell, ultimately ending in
      cell necrosis. In the case of non-biological systems, we present detailed
      protocols relating to quantifying the heat liberated by highly-concentrated NP
      colloids. For biological systems, in the case of in vitro experiments, we
      describe the techniques and conditions which must be adhered to in order to
      effectively expose cancer cells to RF energy without bulk media heating artifacts
      significantly obscuring the data. Finally, we give a detailed methodology for in
      vivo mouse models with ectopic hepatic cancer tumors. 

PMID- 24022385
TI  - Streptococcus bovis bacteraemia: an evaluation of the long-term effect on cardiac
      outcomes.
AB  - INTRODUCTION: Streptococcus bovis can lead to bacteraemia, septicaemia, and
      ultimately endocarditis. The objective of this study was to evaluate the long
      term implications of S. bovis endocarditis on cardiac morbidity and mortality.
      METHODS: A retrospective cohort study was performed between January 2000 and
      March 2009 to assess all patients diagnosed with S. bovis bacteraemia from the
      Belfast Health and Social Care Trust. The primary end-point for cardiac
      investigations was the presence of endocarditis. Secondary end-points included
      referral for cardiac surgery and overall mortality. RESULTS: Sixty-one positive
      S. bovis blood cultures from 43 patients were included. Following
      echocardiography, seven patients were diagnosed with infective endocarditis (16.3
      % of total patients); four patients (9.3 %) had native valve involvement while
      three (7.0 %) had prosthetic valve infection. Five of these seven patients had
      more than one positive S. bovis culture (71.4 %). Three had significant valve
      dysfunction that warranted surgical repair/replacement, one of whom was unfit for
      surgery. There was a 100 % recurrence rate amongst the valve replacement patients
      (n = 2) and six patients with endocarditis had colorectal pathology. Patients
      with endocarditis had similar long-term survival as those with non-endocarditic
      bacteraemia (57.1 % alive vs. 50 % of non-endocarditis patients, p = 0.73).
      CONCLUSION: Streptococcus bovis endocarditis patients tended to have pre-existing
      valvular heart disease and those with prosthetic heart valves had higher surgical
      intervention and relapse rates. These patients experienced a higher rate of co
      existing colorectal pathology but currently have reasonable long-term outcomes.
      This may suggest that they represent a patient population that merits
      consideration for an early surgical strategy to maximise long-term results,
      however, further evaluation is warranted.

PMID- 24022386
TI  - Which of these things is not like the others?

PMID- 24022387
TI  - Respiratory dysrhythmia in dementia with Lewy bodies: a cross-sectional study.
AB  - OBJECTIVES: Dementia with Lewy bodies (DLB) is the second most common form of
      neurodegenerative dementia after Alzheimer's disease (AD). DLB is characterised
      by intracytoplasmic inclusions called Lewy bodies that are often seen in the
      brainstem. Because modulation of the respiratory rhythm is one of the most
      important functions of the brainstem, patients with DLB may exhibit dysrhythmic
      breathing. This hypothesis has not yet been systematically studied. Therefore, we
      evaluated the association between DLB and dysrhythmic breathing. DESIGN: In this
      cross-sectional study consecutive inpatients who were admitted for the evaluation
      of progressive cognitive impairment were enrolled. We assessed breathing
      irregularity using polysomnographic recordings on bed rest with closed eyes,
      without reference to the clinical differentiation among DLB, AD and having no
      dementia. SETTING: Single centre in Japan. PARTICIPANTS: 14 patients with DLB ,
      21 with AD and 12 without dementia were enrolled in this study. PRIMARY OUTCOME
      MEASURES: The coefficient of variation (CV) of the breath-to-breath time was
      calculated. We also examined the amplitude spectrum A(f) obtained using the fast
      Fourier transform and Shannon entropy S of A(f) in patients with DLB compared
      with patients with AD and patients without dementia. RESULTS: The values of CV
      and entropy S were significantly higher in patients with DLB than in patients
      with AD and patients without dementia. No significant differences were observed
      between patients with AD and patients without dementia. CONCLUSIONS: Patients
      with DLB exhibit dysrhythmic breathing compared with patients with AD and
      patients without dementia. Dysrhythmic breathing is a new clinical feature of DLB
      and the spectral analysis of breathing patterns can be clinically useful for the
      diagnostic differentiation of DLB from AD.

PMID- 24022388
TI  - Colorectal cancer survival in the USA and Europe: a CONCORD high-resolution
      study.
AB  - OBJECTIVES: To assess the extent to which stage at diagnosis and adherence to
      treatment guidelines may explain the persistent differences in colorectal cancer
      survival between the USA and Europe. DESIGN: A high-resolution study using
      detailed clinical data on Dukes' stage, diagnostic procedures, treatment and
      follow-up, collected directly from medical records by trained abstractors under a
      single protocol, with standardised quality control and central statistical
      analysis. SETTING AND PARTICIPANTS: 21 population-based registries in seven US
      states and nine European countries provided data for random samples comprising 12
      523 adults (15-99 years) diagnosed with colorectal cancer during 1996-1998.
      OUTCOME MEASURES: Logistic regression models were used to compare adherence to
      'standard care' in the USA and Europe. Net survival and excess risk of death were
      estimated with flexible parametric models. RESULTS: The proportion of Dukes' A
      and B tumours was similar in the USA and Europe, while that of Dukes' C was more
      frequent in the USA (38% vs 21%) and of Dukes' D more frequent in Europe (22% vs
      10%). Resection with curative intent was more frequent in the USA (85% vs 75%).
      Elderly patients (75-99 years) were 70-90% less likely to receive radiotherapy
      and chemotherapy. Age-standardised 5-year net survival was similar in the USA
      (58%) and Northern and Western Europe (54-56%) and lowest in Eastern Europe
      (42%). The mean excess hazard up to 5 years after diagnosis was highest in
      Eastern Europe, especially among elderly patients and those with Dukes' D
      tumours. CONCLUSIONS: The wide differences in colorectal cancer survival between
      Europe and the USA in the late 1990s are probably attributable to earlier stage
      and more extensive use of surgery and adjuvant treatment in the USA. Elderly
      patients with colorectal cancer received surgery, chemotherapy or radiotherapy
      less often than younger patients, despite evidence that they could also have
      benefited.

PMID- 24022389
TI  - Sex work and HIV in Cambodia: trajectories of risk and disease in two cohorts of
      high-risk young women in Phnom Penh, Cambodia.
AB  - OBJECTIVES: HIV prevalence among Cambodian female sex workers (FSW) is among the
      highest in Southeast Asia. We describe HIV prevalence and associated risk
      exposures in FSW sampled serially in Phnom Penh, Cambodia (Young Women's Health
      Study (YWHS)), before and after the implementation of a new law designed to
      combat human trafficking and sexual exploitation. DESIGN: Cross-sectional
      analysis of baseline data from two prospective cohorts. SETTING: Community-based
      study in Phnom Penh, Cambodia. PARTICIPANTS: Women aged 15-29 years, reporting
      >=2 sexual partners in the last month and/or engaged in transactional sex in the
      last 3 months, were enrolled in the studies in 2007 (N=161; YWHS-1), and 2009
      (N=220; YWHS-2) following information sessions where 285 and 345 women attended.
      PRIMARY OUTCOMES: HIV prevalence, sexual risk behaviour, amphetamine-type
      stimulant (ATS) and alcohol use, and work-related factors were compared in the
      two groups, enrolled before and after implementation of the new law. RESULTS:
      Participants in the two cohorts were similar in age (median 25 years), but YWHS-2
      women reported fewer sex partners, more alcohol use and less ATS use. A higher
      proportion of YWHS-2 compared with YWHS-1 women worked in entertainment-based
      venues (68% vs 31%, respectively). HIV prevalence was significantly lower in the
      more recently sampled women: 9.2% (95% CI 4.5% to 13.8%) vs 23% (95% CI 16.5% to
      29.7%). CONCLUSIONS: Sex work context and risk have shifted among young FSW in
      Phnom Penh, following implementation of anti-prostitution and anti-trafficking
      laws. While both cohorts were recruited using the same eligibility criteria, more
      recently sampled women had lower prevalence of sexual risk and HIV infection.
      Women engaging more directly in transactional sex have become harder to sample
      and access. Future prevention research and programmes need to consider how new
      policies and demographic changes in FSW impact HIV transmission.

PMID- 24022390
TI  - Randomised controlled trial comparing hypnotherapy versus gabapentin for the
      treatment of hot flashes in breast cancer survivors: a pilot study.
AB  - OBJECTIVES: To compare the efficacy of hypnotherapy versus gabapentin for the
      treatment of hot flashes in breast cancer survivors, and to evaluate the
      feasibility of conducting a clinical trial comparing a drug with a complementary
      or alternative method (CAM). DESIGN: Prospective randomised trial. SETTING:
      Breast health centre of a tertiary care centre. PARTICIPANTS: 15 women with a
      personal history of breast cancer or an increased risk of breast cancer who
      reported at least one daily hot flash. INTERVENTIONS: Gabapentin 900 mg daily in
      three divided doses (control) compared with standardised hypnotherapy.
      Participation lasted 8 weeks. OUTCOME MEASURES: The primary endpoints were the
      number of daily hot flashes and hot flash severity score (HFSS). The secondary
      endpoint was the Hot Flash Related Daily Interference Scale (HFRDIS). RESULTS: 27
      women were randomised and 15 (56%) were considered evaluable for the primary
      endpoint (n=8 gabapentin, n=7 hypnotherapy). The median number of daily hot
      flashes at enrolment was 4.5 in the gabapentin arm and 5 in the hypnotherapy arm.
      HFSS scores were 7.5 in the gabapentin arm and 10 in the hypnotherapy arm. After
      8 weeks, the median number of daily hot flashes was reduced by 33.3% in the
      gabapentin arm and by 80% in the hypnotherapy arm. The median HFSS was reduced by
      33.3% in the gabapentin arm and by 85% in the hypnotherapy arm. HFRDIS scores
      improved by 51.6% in the gabapentin group and by 55.2% in the hypnotherapy group.
      There were no statistically significant differences between groups. CONCLUSIONS:
      Hypnotherapy and gabapentin demonstrate efficacy in improving hot flashes. A
      definitive trial evaluating traditional interventions against CAM methods is
      feasible, but not without challenges. Further studies aimed at defining evidence
      based recommendations for CAM are necessary. TRIAL REGISTRATION:
      clinicaltrials.gov (NCT00711529).

PMID- 24022392
TI  - Trajectories of recovery among homeless adults with mental illness who
      participated in a randomised controlled trial of Housing First: a longitudinal,
      narrative analysis.
AB  - OBJECTIVES: This study used longitudinal, narrative data to identify trajectories
      of recovery among homeless adults with mental illness alongside the factors that
      contribute to positive, negative, mixed or neutral trajectories over time. We
      expected that participants who received Housing First (HF) would describe more
      positive trajectories of recovery than those who were assigned to Treatment as
      Usual (TAU; no housing or support provided through the study). DESIGN: Narrative
      interview data were collected from participants at baseline and 18 months after
      random assignment to HF or TAU. SETTING: Participants were sampled from the
      community in Vancouver, British Columbia. PARTICIPANTS: Fifty-four participants
      were randomly and purposively selected from the larger trial; 52 were interviewed
      at baseline and 43 were reinterviewed 18 months after randomisation. METHOD:
      Semistructured interviews were conducted at both time points. For each
      participant, paired baseline and follow-up narratives were classified as
      positive, negative, mixed or neutral trajectories of recovery, and thematic
      analysis was used to identify the factors underlying different trajectories.
      RESULTS: Participants assigned to HF (n=28) were generally classified as positive
      or mixed trajectories; those assigned to TAU (n=15) were generally classified as
      neutral or negative trajectories. Positive trajectories were characterised by a
      range of benefits associated with good-quality, stable housing (eg, reduced
      substance use, greater social support), positive expressions of identity and the
      willingness to self-reflect. Negative, neutral and mixed trajectories were
      characterised by hopelessness ('things will never get better') related to
      continued hardship (eg, eviction, substance use problems), perceived failures and
      loss. CONCLUSIONS: HF is associated with positive trajectories of recovery among
      homeless adults with mental illness. Those who did not receive housing or support
      continued to struggle across a wide range of life domains. Findings are discussed
      with implications for addressing services and broader social change in order to
      benefit this marginalised population.

PMID- 24022391
TI  - The proportion of clinically relevant alarms decreases as patient clinical
      severity decreases in intensive care units: a pilot study.
AB  - OBJECTIVES: To determine (1) the proportion and number of clinically relevant
      alarms based on the type of monitoring device; (2) whether patient clinical
      severity, based on the sequential organ failure assessment (SOFA) score, affects
      the proportion of clinically relevant alarms and to suggest; (3) methods for
      reducing clinically irrelevant alarms in an intensive care unit (ICU). DESIGN: A
      prospective, observational clinical study. SETTING: A medical ICU at the
      University of Tokyo Hospital in Tokyo, Japan. PARTICIPANTS: All patients who were
      admitted directly to the ICU, aged >=18 years, and not refused active treatment
      were registered between January and February 2012. METHODS: The alarms, alarm
      settings, alarm messages, waveforms and video recordings were acquired in real
      time and saved continuously. All alarms were annotated with respect to technical
      and clinical validity. RESULTS: 18 ICU patients were monitored. During 2697
      patient-monitored hours, 11 591 alarms were annotated. Only 740 (6.4%) alarms
      were considered to be clinically relevant. The monitoring devices that triggered
      alarms the most often were the direct measurement of arterial pressure (33.5%),
      oxygen saturation (24.2%), and electrocardiogram (22.9%). The numbers of relevant
      alarms were 12.4% (direct measurement of arterial pressure), 2.4% (oxygen
      saturation) and 5.3% (electrocardiogram). Positive correlations were established
      between patient clinical severities and the proportion of relevant alarms. The
      total number of irrelevant alarms could be reduced by 21.4% by evaluating their
      technical relevance. CONCLUSIONS: We demonstrated that (1) the types of devices
      that alarm the most frequently were direct measurements of arterial pressure,
      oxygen saturation and ECG, and most of those alarms were not clinically relevant;
      (2) the proportion of clinically relevant alarms decreased as the patients'
      status improved and (3) the irrelevance alarms can be considerably reduced by
      evaluating their technical relevance.

PMID- 24022394
TI  - Third ventricular enlargement in early stages of multiple sclerosis is a
      predictor of motor and neuropsychological deficits: a cross-sectional study.
AB  - OBJECTIVES: Whether transcranal sonography (TCS) depicted third ventricular
      enlargement as a sign of brain atrophy is predictive for neuropsychological
      deficits in mildly affected patients with multiple sclerosis (MS). DESIGN: Cross
      sectional study of a cohort of mildly diseased patients with MS. SETTING:
      Neurological MS outpatient clinic at a large teaching hospital in central Europe.
      PARTICIPANTS: Fifty-four patients with MS (16 men, 38 women, mean age 40+/-10
      years, mean disease duration 6+/-5 years; mean Expanded Disability Status Scale
      2+/-1.3) and 33 healthy controls (12 men, 21 women; 38+/-11 years) underwent
      clinical examination, an assessment of the third ventricle width by means of TCS
      and the Brief Repeatable Battery of Neuropsychological tests for MS, the 25-Feet
      Foot Walk test, the 9-Hole PEG test, the Beck Depression Inventory and a
      quantitative fatigue assessment. Statistical analysis was performed with
      univariate correlation and thereafter by stepwise regression analysis. RESULTS:
      Patients' mean third ventricular width (3.9+/-1.6 mm) was significantly wider
      compared to controls (3.4+/-0.8 mm). Using stepwise regression analysis models
      with age, MS duration, third ventricle width and quantitative fatigue assessment
      as baseline variables, an increasing third ventricle width significantly
      correlated with the target variables worsening of motor deficits (p<0.002),
      worsening of verbal recall (p<0.04) and of visual spatial recall (p<0.005).
      Severity of depression and of fatigue was unrelated to third ventricular width.
      CONCLUSIONS: In this cohort of patients with MS with mild disease, third
      ventricular enlargement was indicative for motor deficits and cognitive
      impairment, even after considering fatigue as a relevant comorbidity. Third
      ventricular enlargement by means of TCS seems to be a useful, clinically
      meaningful parameter to stage patients' disease severity. Follow-up studies must
      show whether an intraindividual future third ventricular increase indeed signals
      larger cognitive impairment.

PMID- 24022393
TI  - Long-term sustained remission in a cohort study of patients with rheumatoid
      arthritis: choice of remission criteria.
AB  - OBJECTIVES: Remission is a widely accepted goal for treatment of rheumatoid
      arthritis (RA) but has to be sustained to arrest joint damage and disability.
      However, appropriate criteria for the assessment of sustained remission in long
      term studies are not established. Therefore, we have compared the disease
      activity score calculated on 28 joints (DAS28) remission criterion, the
      Simplified Disease Activity Index less than 3.3 remission criterion (SDAI Cr) and
      the new Boolean-based set of criteria (Boolean Cr), and assessed the association
      of these criteria with radiographic and functional outcome. DESIGN: Prospective,
      long-term observational study of patients with early RA. SETTING: Secondary level
      of care; six participating centres from southern Sweden; both urban and rural
      populations. PARTICIPANTS: 698 patients were consecutively included in the study
      and 527 remained at the 8-year follow-up visit. Almost all patients were
      Caucasians, of which 64% were women. To be included, a patient, 18 years or
      older, had to fulfil the 1987 American College of Rheumatology criteria for RA
      and have a disease duration of no more than 1 year. RESULTS: Sustained remission
      was most common by the DAS28 Cr (14%), while 3% met the Boolean Cr and 5% the
      SDAI Cr, the latter figures increasing to 9% and 8%, respectively, when the
      patient's global assessment was excluded. Radiographic joint damage was common
      but least pronounced in patients in sustained remission by all criteria.
      Sustained remission was associated with rapid and lasting improvement in function
      assessed by the Health Assessment questionnaire, irrespective of criteria.
      CONCLUSIONS: The DAS28 Cr acquired more patients in sustained remission compared
      with the other criteria. In spite of that, radiographic damage and disability
      were not worse than that seen by other criteria and the patients' perspective was
      preserved. The DAS28 Cr may therefore still be used in long-term observational
      studies until more accurate criteria are available.

PMID- 24022395
TI  - Offering fragile X syndrome carrier screening: a prospective mixed-methods
      observational study comparing carrier screening of pregnant and non-pregnant
      women in the general population.
AB  - INTRODUCTION: Fragile X syndrome (FXS) is the leading cause of inherited
      intellectual and developmental disability. Policy development relating to carrier
      screening programmes for FXS requires input from large studies examining not only
      test uptake but also psychosocial aspects. This study will compare carrier
      screening in pregnant and non-pregnant populations, examining informed decision
      making, psychosocial issues and health economics. METHODS AND ANALYSIS: Pregnant
      and non-pregnant women are being recruited from general practices and obstetric
      services. Women receive study information either in person or through clinic mail
      outs. Women are provided pretest counselling by a genetic counsellor and make a
      decision about testing in their own time. Data are being collected from two
      questionnaires: one completed at the time of making the decision about testing
      and the second 1 month later. Additional data are gathered through qualitative
      interviews conducted at several time points with a subset of participating women,
      including all women with a positive test result, and with staff from recruiting
      clinics. A minimum sample size of 500 women/group has been calculated to give us
      88% power to detect a 10% difference in test uptake and 87% power to detect a 10%
      difference in informed choice between the pregnant and non-pregnant groups.
      Questionnaire data will be analysed using descriptive statistics and multivariate
      logistic regression models. Interview data will be thematically analysed.
      Willingness-to-pay and cost effectiveness analyses will also be performed.
      Recruitment started in July 2009 and data collection will be completed by
      December 2013. ETHICS AND DISSEMINATION: Ethics approval has been granted by the
      Universities of Melbourne and Western Australia and by recruiting clinics, where
      required. Results will be reported in peer-reviewed publications, conference
      presentations and through a website http://www.fragilexscreening.net.au. The
      results of this study will make a significant contribution to discussions about
      the wider introduction of population carrier screening for FXS.

PMID- 24022396
TI  - Coralslurrinella hongkonensis gen. nov., sp. nov., a novel bacterium in the
      family Psychromonadaceae, isolated from the coral Platygyra carnosus.
AB  - A novel bacterial strain, JLT2006T, was isolated from the scleractinian coral
      Platygyra carnosus, located in Hong Kong, China. Cells of this strain were Gram
      negative, rod-shaped or oval-shaped and motile by the means of polar flagella.
      They formed faint-yellow, round colonies on marine agar medium. Phylogenetic
      analyses based on the 16S rRNA gene sequence indicated that the strain JLT2006T
      belonged to the class Gammaproteobacteria and was most closely related to
      Alteromonas-like bacteria of the genera Psychromonas, Pseudoalteromonas,
      Moritella, Shewanella and Ferrimonas, with less than 93 % sequence similarity.
      The predominant fatty acids were identified as C18:1x7c/C18:1x6c (23.0 %),
      C16:1x7c/C16:1x6c (18.2 %) and C16:0 (16.4 %). The quinone was menaquinone-7 (100
      %). The polar lipids were determined to be phosphatidylglycerol,
      phosphatidylethanolamine, phospholipid, glycolipid and lipid. The genomic DNA G?C
      content was 40.3 mol%. Based on the 16S rRNA gene sequence as well as the
      physiological and biochemical features that separate the strain JLT2006T from
      other recognized bacteria, a novel species of a new genus with the name
      Coralslurrinella hongkonensis gen. nov., sp. nov. is proposed. The type strain is
      JLT2006T (=JCM 18796T = CGMCC 1.10992T).

PMID- 24022397
TI  - Pseudoalteromonas xishaensis sp. nov., isolated  from Acanthaster planci in the
      Xisha islands.
AB  - A Gram-negative, aerobic, motile by means of single polar flagellum, short rod
      shaped marine bacterium, designated strain E418T, was isolated from the spines on
      the body surface of starfish Acanthaster planci in the Xisha islands, China.
      Cells of strain E418T were found to grow optimally at pH 7-8, at 25-37  degrees
      C, and in the presence of 2-5 % (w/v) NaCl. Phylogenetic analysis based on the
      comparison of 16S rRNA gene sequences revealed that strain E418T is a member of
      the genus Pseudoalteromonas. The closest relative to this strain was found to be
      P. ruthenica LMG 19699T, with a similarity level of 97.7 %. DNA relatedness
      between the novel isolate and this phylogenetically related species was 57.4 %.
      Strain E418T decomposed Tween 80, gelatin, and casein, but was unable to
      decompose starch and grow on DNase Agar. The cellular fatty acid profile
      consisted of significant amounts of C16:1omega7c/C16:1omega6c,
      C18:1omega7c/C18:1omega6c, C16:0, and C17:1omega8c. The G+C content of DNA of
      this strain was determined to be 46.7 mol%. Phenotypic characteristics,
      phylogenetic analysis and DNA-DNA relatedness data suggest that strain E418T
      represents a novel species of the genus Pseudoalteromonas, for which the name
      Pseudoalteromonas xishaensis sp. nov. is proposed. The type strain of P.
      xishaensis is strain E418T (DSM 25588T = NBRC 108846T = CCTCC AB 2011177T).

PMID- 24022398
TI  - Synthetic nucleic acids delivered by exosomes: a potential therapeutic for
      generelated metabolic brain diseases.
AB  - Many brain diseases, including Alzheimer's disease, are associated with genetic
      abnormalities. The search for more effective therapeutic approaches involving
      nucleic acids like interfering RNA, antisense oligonucleotides and mRNA has drawn
      much attention in the development of alternatives to virus-based gene therapy.
      Potentially, nucleic acids could not only specifically down-regulate and degrade
      misfolded proteins, but also relieve protein deficiencies by directing the
      translation of functional proteins. However, clinical applications have been
      stalled by the lack of proper delivery systems. Exosomes are nano-scale
      extracellular vesicles secreted by nearly all somatic cells. Recent work has
      revealed that exosomes play special roles in intercellular communication via the
      horizontal transfer of various RNAs among cells. Recently, the use of exosomes
      for the delivery of therapeutic nucleic acids to targeted cells has been
      demonstrated to be a practical approach. Here, we briefly review the general
      properties of exosomes and introduce three therapeutic nucleic acids. Based upon
      comparison with other delivery methods, exosomes are proposed as an ideal nucleic
      acid delivery system for metabolic brain disease therapy.

PMID- 24022399
TI  - Quantification of blood dendritic cells in colorectal cancer patients during the
      course of disease.
AB  - Colorectal cancer is a malignancy with poor prognosis that might be associated
      with defective immune function. The aim of the present study was to investigate
      circulating dendritic cells in colorectal cancer patients, in order to contribute
      to elucidate tumor-escape mechanisms and to point out a possible correlation with
      the clinical condition of the disease. Therefore, we enumerated ex vivo myeloid
      and plasmacytoid dendritic cells, through multicolor flow cytometry, in 26
      colorectal patients and 33 healthy controls. Furthermore we performed several
      analyses at determined time points in order to define the immunological trend of
      cancer patients after surgery and other conventional treatments. At the pre
      operative time point the absolute number of plasmacytoid dendritic cells in
      cancer patients was significantly reduced in comparison to controls, this result
      being mainly referred to stage III-IV patients. The number of myeloid dendritic
      cells did not show any significant difference compared to healthy controls;
      interestingly the expression of the tolerogenic antigen CD85k was significantly
      higher on cancer patients' myeloid dendritic cells than controls'. At the
      following samplings, circulating dendritic cell absolute number did not show any
      difference compared to controls. Conclusively the impairment of the number of
      circulating dendritic cells may represent one of the tumor escape mechanisms
      occurring in colorectal cancer. These alterations seem to be correlated to cancer
      progression. Our work sheds light on one of dendritic cell-based tumor immune
      escape mechanisms. This knowledge may be useful to the development of more
      effective immunotherapeutic strategies.

PMID- 24022400
TI  - Ephrin receptor (Eph) -A1, -A2, -A4 and -A7 expression in mobile tongue squamous
      cell carcinoma: associations with clinicopathological parameters and patients
      survival.
AB  - Ephrin receptors (Ephs) are frequently overexpressed in a wide variety of human
      malignant tumors, being associated with tumor growth, invasion, metastasis and
      angiogenesis. The present study aimed to evaluate the clinical significance of
      Eph-A1, -A2, -A4 and -A7 protein expression in mobile tongue squamous cell
      carcinoma (SCC). Eph-A1, -A2, -A4 and -A7 protein expression was assessed
      immunohistochemically on 37 mobile tongue SCC tissue samples and was analyzed in
      relation with clinicopathological characteristics, overall and disease-free
      patients' survival. All the examined mobile tongue SCC cases were found positive
      for Eph-A1, -A2, -A4 and -A7. Significant associations were noted between high
      Eph-A1, -A4 and -A7 expression and absence of lymph node metastases (p = 0.0263,
      p = 0.0461 and p = 0.0461, respectively). High Eph-A1, -A2 and -A7 expression was
      significantly more frequently observed in patients presenting absence of vascular
      invasion (p = 0.0444), dense stromal inflammatory reaction (p = 0.0063) and
      female gender (p = 0.0327), respectively. Mobile tongue SCC patients with high
      Eph-A7 expression presented longer overall and disease-free survival compared to
      those with low Eph-A7 expression (log-rank test, p = 0.0093 and p = 0.0164,
      respectively). In multivariate analysis, Eph-A7 expression was identified as
      independent prognostic factor of overall survival (Cox-regression analysis, p =
      0.0426). The present study supported evidence that Ephs may participate in the
      malignant transformation of mobile tongue SCC, reinforcing their utility as
      clinical markers for patients' management and prognosis, as also as targets for
      potential therapeutic intervention in tongue chemoprevention.

PMID- 24022401
TI  - Periostin promotes the generation of fibrous membranes in proliferative
      vitreoretinopathy.
AB  - Proliferative vitreoretinopathy (PVR) is a severe, vision-threatening disorder
      characterized by the fibrous membrane formation that leads to tractional retinal
      detachment. There has been no effective therapeutic approach other than
      vitreoretinal surgery. In this study, DNA microarray analysis of the fibrous
      membranes revealed significant up-regulation of periostin. We also found
      increased periostin expression in the vitreous and retinal pigment epithelial
      (RPE) cells from fibrous membranes of PVR patients. In vitro, periostin increased
      proliferation, adhesion, migration, and collagen production in RPE cells through
      integrin alphaV-mediated FAK and AKT phosphorylation. Periostin blockade
      suppressed migration and adhesion induced by TGFbeta2 and PVR vitreous. In vivo,
      periostin inhibition had the inhibitory effect on progression of experimental PVR
      in rabbit eyes without affecting the viability of retinal cells. These results
      identified periostin as a pivotal molecule for fibrous membrane formation as well
      as a promising therapeutic target for PVR.

PMID- 24022402
TI  - A novel intronic promoter of the Crem gene induces small ICER (smICER) isoforms.
AB  - The transcription factors cAMP-responsive element binding protein (CREB) and cAMP
      responsive element modulator (CREM) regulate gene transcription in response to
      elevated cAMP levels. The Crem isoform inducible cAMP early repressor (Icer) is
      transcribed by the internal promoter P2 as a critical regulator of multiple
      cellular processes. Here, we describe a novel inducible Crem isoform, small Icer
      (smIcer), regulated by a newly identified promoter (P6). ChIP revealed binding of
      CREB to P6 in human and mouse myocardium. P6 activity was induced by
      constitutively active CREB or stimulation of adenylyl cyclase. In mice, smIcer
      mRNA was ubiquitously expressed and transiently induced by beta-adrenoceptor
      stimulation e.g., in heart and lung. SmICER repressed both basal and cAMP-induced
      activities of P6 and P2 promoters. Stimulation of adenylyl cyclase induced P2 and
      P6 in cell type-specific manner. Alternative translational start sites resulted
      in three different smICER proteins, linked to increased apoptosis sensitivity. In
      conclusion, the Crem gene provides two distinct and mutually controlled
      mechanisms of a cAMP-dependent induction of transcriptional repressors. Our
      results suggest not only that smICER is a novel regulator of cAMP-mediated gene
      regulation, but also emphasize that biological effects that have been ascribed
      solely to ICER, should be revised with regard to smICER.

PMID- 24022403
TI  - High cortisol responses identify propensity for obesity that is linked to
      thermogenesis in skeletal muscle.
AB  - Subjects characterized as cortisol high responders (HRs) consume more calories
      after stress, but it is unknown whether cortisol responsiveness predicts a
      propensity for obesity. Female sheep with either high or low cortisol responses
      to adrenocorticotropin (ACTH) were identified. Body composition was similar in
      HRs and cortisol low responders (LRs), but the HRs had greater (P<0.01) adiposity
      than did the LRs (40.5+/-0.7 vs. 35.8+/-1.4%) after high-energy feeding, despite
      comparable food intake. Postprandial thermogenesis in muscle temperature was 0.8
      +/- 0.08 degrees C higher in the LRs than in the HRs (P<0.01), whereas feeding
      induced changes in fat temperature were similar. Leptin and insulin sensitivity
      were similar in the HRs and LRs. Feeding lowered (P<0.001) the respiratory
      control ratio in muscle (HRs 9.2+/-0.8-5.2+/-1.2; LRs 8.4+/-0.5-5.2+/-0.7),
      indicative of increased uncoupled respiration. Also in muscle, the feeding
      induced increases in uncoupling protein (UCP)-3 (fold increase: HRs, 2.4; LRs,
      2.0), ryanodine 1 receptor (RyR1; fold increase: HRs 3.1; LRs 2.1), and
      sarcoendoplasmic reticulum Ca(2+)-dependent ATPase (fold increase: HRs 1.5; LRs
      1.6) were equivalent in the HRs and LRs. Sequencing of mitochondrial DNA revealed
      no haplotypic differences between the 2 groups. We conclude that predisposition
      to obesity can be predicted by cortisol responsiveness to an ACTH challenge and
      that the response is due to innate differences in muscle thermogenesis.

PMID- 24022405
TI  - High-density lipoproteins augment hypoxia-induced angiogenesis via regulation of
      post-translational modulation of hypoxia-inducible factor 1alpha.
AB  - Increasing evidence suggests that high-density lipoproteins (HDLs) promote
      hypoxia-induced angiogenesis. The hypoxia-inducible factor 1alpha (HIF
      1alpha)/vascular endothelial growth factor (VEGF) pathway is important in hypoxia
      and is modulated post-translationally by prolyl hydroxylases (PHD1-PHD3) and E3
      ubiquitin ligases (Siah1 and Siah2). We aimed to elucidate the mechanisms by
      which HDLs augment hypoxia-induced angiogenesis. Preincubation (16 h) of human
      coronary artery endothelial cells with reconstituted high-density lipoprotein
      (rHDL) containing apolipoprotein A-I (apoA-I) and phosphatidylcholine (20 MUM,
      final apoA-I concentration), before hypoxia, increased Siah1 (58%) and Siah2
      (88%) mRNA levels and suppressed PHD2 (32%) and PHD3 (45%) protein levels
      compared with hypoxia-induced control levels. After Siah1/2 small interfering RNA
      knockdown, rHDL was unable to suppress PHD2/3 and failed to induce HIF-1alpha,
      VEGF, and tubulogenesis in hypoxia. Inhibition of the upstream
      phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway also abrogated the
      effects of rHDL. Furthermore, knockdown of the scavenger receptor SR-BI
      attenuated rHDL-induced elevations in Siah1/2 and tubulogenesis in hypoxia,
      indicating that SR-BI plays a key role. Finally, the importance of VEGF in
      mediating the ability of rHDL to drive hypoxia-induced angiogenesis was confirmed
      using a VEGF-neutralizing antibody. In summary, rHDL augments the HIF-1alpha/VEGF
      pathway via SR-BI and modulation of the post-translational regulators of HIF
      1alpha (PI3K/Siahs/PHDs). HDL-induced augmentation of angiogenesis in hypoxia may
      have implications for therapeutic modulation of ischemic injury.

PMID- 24022404
TI  - Myristoylated alanine-rich C kinase substrate coordinates native TRPC1 channel
      activation by phosphatidylinositol 4,5-bisphosphate and protein kinase C in
      vascular smooth muscle.
AB  - Canonical transient receptor potential 1 (TRPC1) Ca(2+)-permeable cation channels
      contribute to vascular tone and blood vessel remodeling and represent potential
      therapeutic targets for cardiovascular disease. Protein kinase C (PKC) and
      phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] are obligatory for native TRPC1
      channel activation in vascular smooth muscle cells (VSMCs) but how PKC and
      PI(4,5)P2 act together to induce channel gating remains unresolved. The present
      study reveals that myristoylated alanine-rich C kinase substrate (MARCKS) protein
      coordinates activation of TRPC1 channels by PKC and PI(4,5)P2. TRPC1 channels and
      MARCKS form signaling complexes with PI(4,5)P2 bound to MARCKS; in this
      configuration TRPC1 channels are closed. Activators of TRPC1 channels induce PKC
      phosphorylation of TRPC1 proteins, which causes dissociation of TRPC1 subunits
      from MARCKS and release of PI(4,5)P2 from MARCKS; PI(4,5)P2 subsequently binds to
      TRPC1 subunits to induce channel opening. Calmodulin acting at, or upstream of,
      MARCKS is also required for TRPC1 channel opening through a similar gating
      mechanism involving PKC and PI(4,5)P2. These novel findings show that MARCKS
      coordinates native TRPC1 channel activation in VSMCs by acting as a reversible
      PI(4,5)P2 buffer, which is regulated by PKC-mediated TRPC1 phosphorylation.
      Moreover, our data provide evidence that PI(4,5)P2 is a gating ligand of TRPC1
      channels.

PMID- 24022406
TI  - Assessing adherence to oral chemotherapy using different measurement methods:
      Lessons learned from capecitabine.
AB  - PURPOSE: Adherence to oral medication is important in oncology. Few studies have
      evaluated adherence with cancer agents such as capecitabine, which is given on a
      complicated schedule. Furthermore, little guidance exists regarding the best
      methods for monitoring adherence with oral cancer drugs. The purpose of our study
      was to evaluate adherence to capecitabine using several accepted measures.
      PATIENTS AND METHODS: Patients treated with capecitabine for gastrointestinal
      cancers were included in this prospective cohort study. Adherence was evaluated
      during two consecutive cycles of capecitabine using three assessment methods:
      self-report, pill count, and use of a microelectronic monitoring system. The
      primary endpoint was proportion of patients adherent to capecitabine (>80% of
      adherence according to the three methods of measurement); the secondary objective
      was to compare the three methods of measurement. RESULTS: Nineteen patients were
      accrued to this study. Further accrual was stopped after the first planned
      analysis, because 18 and 19 patients were adherent by self-report and pill count,
      respectively. The overall adherence rates were 99, 100, and 61% with self-report,
      pill count, and microelectronic monitoring system cap, respectively. Ten (53%)
      patients were classified as nonadherent (<80% of adherence according to at least
      one method of measurement), but four of them transferred their pills into another
      medication container suggesting that measurement of adherence using
      microelectronic monitoring system technology may not be useful. CONCLUSION: While
      we did not identify a major adherence issue with capecitabine in our study, it
      provides insight into problems associated with measurement of adherence in
      oncology and suggests that combining measures of adherence maximizes accuracy.

PMID- 24022407
TI  - New and emerging therapies for advanced or metastatic soft tissue sarcoma.
AB  - Soft tissue sarcomas include a rare variety of tumors, which require a
      multidisciplinary approach to treatment. Patients with advanced or metastatic
      disease are typically treated with anthracycline-based therapy, but these
      chemotherapy regimens are associated with poor response rates and average
      survival duration of one year. Much attention has been turned toward
      overexpressed gene pathways, and utilizing targeted therapies to inhibit tumor
      growth. Many new and approved targeted therapies and chemotherapy agents are
      currently in clinical and preclinical studies for soft tissue sarcoma. As the
      results of these studies are reported, we hope to see improved response rates and
      less toxicity, both in the frontline setting and for patients with advanced
      disease. This article will review the available data for some of the more
      promising therapies for advanced or metastatic soft tissue sarcomas. 

PMID- 24022408
TI  - The impact of pre-transplant valganciclovir on early cytomegalovirus reactivation
      after allogeneic hematopoietic stem cell transplantation.
AB  - Cytomegalovirus reactivation is a common complication of allogeneic hematopoietic
      stem cell transplant. The use of pre-transplant valganciclovir during the
      conditioning regimen followed by preemptive therapy has been used in an attempt
      to reduce the rate of early cytomegalovirus reactivation, but efficacy data are
      lacking. In this retrospective study, we evaluated the impact of pre-transplant
      valganciclovir during the conditioning regimen followed by a preemptive approach
      on the rate of early cytomegalovirus reactivation through day 100. The rate of
      cytomegalovirus reactivation through day 100 was 41% in the no-valganciclovir
      group compared to 46% in the valganciclovir group (p = 0.4). Interestingly,
      median time to cytomegalovirus reactivation was earlier in the no-valganciclovir
      group compared to the valganciclovir group (26 vs. 34 days; p = 0.008) and there
      was a trend toward a higher rate of cytomegalovirus disease through day 100 in
      the no-valganciclovir group (0.7% valganciclovir vs. 4% no-valganciclovir; p =
      0.1). Day 100 survival was similar between the groups (90% valganciclovir vs. 91%
      no-valganciclovir; p = 0.8). Although the time to cytomegalovirus reactivation is
      significantly longer in the valganciclovir group, this did not impact the rate of
      cytomegalovirus reactivation or survival by day 100 suggesting that other
      strategies need to be explored. 

PMID- 24022410
TI  - [Longitudinal model in pain medicine (LoMoS). Needs assessment and learning
      developement of learning goals].
AB  - BACKGROUND: Pain medicine as an interdisciplinary, multifaceted field has not yet
      been assigned the status of a separate medical subject in the curriculum of
      medical schools in Germany. Pain medicine is often taught by anesthesiologists,
      neurologists, orthopedic or neurological surgeons either by assignment by the
      Dean's office or because of their own enthusiasm. In the near future pain
      medicine as an interdisciplinary course will be mandatory in undergraduate
      medical education. The authors were interested to investigate the needs and
      demands of both students and instructors from theoretical and clinical fields in
      order to develop a longitudinal pain medicine curriculum. METHODS: Based on
      Kern's curriculum development model, the opinions of students and instructors
      were investigated: quantitative items were analyzed using Student's t-test for
      independent variables and heterogenic variance and the content of free text
      answers was analyzed by forming subsets of similar or identical answers. A
      concise curriculum was developed. RESULTS: Students from advanced classes noted a
      bigger discrepancy between the needs formulated and what was actually offered as
      compared to younger students. Instructors from different theoretical and clinical
      specialties were unaware of the topics of colleagues from other departments. The
      analysis of written answers revealed a different understanding of the term pain
      medicine. CONCLUSION: At the Hannover Medical School, a standardized needs
      assessment helped to develop LoMoS, the longitudinal pain medicine curriculum,
      which may also serve as a model for other medical faculties. Students required
      more practical instruction and teachers were interested in improving networking
      and discussion among specialists.

PMID- 24022412
TI  - "To all the bright lights in the field... Can we count you in?".

PMID- 24022411
TI  - [The rubber hand illusion in patients with complex regional pain syndrome.
      Successful illusion induction shows multisensory integration].
AB  - Next to neurogenic inflammation and pathological sympathetic-afferent coupling,
      functional imaging studies have shown the crucial role of maladaptive cortical
      reorgansation in the pathophysiology of CRPS. Bilateral neuroplastic alterations
      in the somatosensory cortex seem to play a substantial role in the dysfunctional
      sensory processing of stimuli. The aim was to investigate the multimodal
      integration of sensory and visual stimuli into the body scheme and the influence
      of higher cognitive body representation in the integration of multimodal schema,
      body relevant stimuli in patients with CRPS. The investigated sample included 24
      patients suffering from CRPS of the upper extremities, 21 patients with chronic
      hand pain of other origins and 24 healthy probands. The rubber hand illusion was
      carried out for the first time in patients with complex regional pain syndrome
      (CRPS). The reprentations show that the patients can integrate a rubber hand in
      their body representation to the same degree as healthy patients. The intact
      experience of the rubber hand illusion by CRPS patients indicates that the
      integration of congruent visual and tactile stimuli in CRPS is intact.

PMID- 24022413
TI  - NAON Foundation... We're having our 20th birthday, will you join the celebration?

PMID- 24022414
TI  - Introduction: NAON Surgical Site Infection Prevention Clinical Practice
      Guideline.
AB  - According to the , "Clinical practice guidelines are statements that include
      recommendations intended to optimize patient care. They are informed by a
      systematic review of evidence and an assessment of the benefits and harms of
      alternative care options." Nursing clinical practice guidelines provide defined
      best practice modalities that assist nurses in the diagnosis, management, or
      prevention of specific healthcare conditions, while including recommendations
      that are derived from the highest levels of evidence. These levels of evidence
      include high-quality systematic reviews of current literature, meta-analyses, or
      well-designed clinical trials. 

PMID- 24022415
TI  - Clinical practice guideline surgical site infection prevention.

PMID- 24022417
TI  - Proximal humerus fractures.
AB  - Proximal humerus fractures are among the most common fractures associated with
      osteoporosis. With an aging population, incidence of these fractures will only
      increase. The proximal humerus not only forms the lateral portion of the shoulder
      articulation but also has significant associations with musculoskeletal and
      neurovascular structures. As a result, fractures of the proximal humerus can
      significantly impact not only the function of the shoulder joint, but the health
      and function of the entire upper extremity as well. Understanding of these
      fractures, the management options, and associated nursing care, can help reduce
      morbidity rate and improve functional outcomes. 

PMID- 24022420
TI  - An empirical study using range of motion and pain score as determinants for
      continuous passive motion: outcomes following total knee replacement surgery in
      an adult population.
AB  - BACKGROUND: The continuous passive motion (CPM) machine is one means by which to
      rehabilitate the knee after total knee replacement surgery. PURPOSE: This study
      sought to determine which total knee replacement patients, if any, benefit from
      the use of the CPM machine. METHODS: For the study period, most patients received
      active physical therapy. Patients were placed in the CPM machine if, on
      postoperative day 1, they had a range of motion less than or equal to 45 degrees 
      and/or pain score of 8 or greater on a numeric rating scale of 0-10, 0 being no
      pain and 10 being the worst pain. RESULTS: Both groups of patients healed at
      similar rates. The incidence of adverse events, length of stay, and functional
      outcomes was comparable between groups. CONCLUSION: Given the demonstrated lack
      of relative benefit to the patient and the cost of the CPM, this study supported
      discontinuing the routine use of the CPM.

PMID- 24022421
TI  - Medical adhesive safety summit.

PMID- 24022422
TI  - Medical adhesives and patient safety: state of the science: consensus statements
      for the assessment, prevention, and treatment of adhesive-related skin injuries.
AB  - Skin injury related to medical adhesive usage is a prevalent but underrecognized
      complication that occurs across all care settings and among all age groups. If
      proper technique for application and/or removal of adhesive products is not used,
      tissue trauma can occur, impacting patient safety and quality of life and
      increasing healthcare costs. Little guidance exists in the literature regarding
      appropriate selection and proper use of adhesive products to minimize medical
      adhesive-related skin injury, as well as best practices for skin care preventive
      strategies, application and removal techniques, and assessment and treatment of
      such injuries. In an effort to define best practices for prevention of such
      injury, a consensus panel of 23 recognized key opinion leaders convened to
      establish consensus statements on the assessment, prevention, and treatment of
      medical adhesive-related skin injury. The consensus summit was held in December
      2012 and was made possible by an unrestricted educational grant from 3M. This
      document details the consensus definitions and statements and identifies research
      priorities for development of new adhesive technologies and protocols for skin
      protection. 

PMID- 24022423
TI  - The effect of caffeine on postoperative urinary retention after joint replacement
      surgery.
AB  - BACKGROUND: Review of data on complications following joint replacement surgery
      revealed that urinary retention is a potential cause of increased morbidity.
      Repeat catheterizations, urinary tract infections, and possible infection of the
      prosthetic joint can result in a prolonged hospital length of stay. This study
      examined the effect of warm caffeinated coffee on a patient's ability to
      spontaneously void after indwelling catheter removal and the correlation between
      bladder volume and the ability to void spontaneously. METHODS: This was a
      randomized, controlled, pilot study of subjects who underwent unilateral total
      knee arthroplasty or total hip arthroplasty. The indwelling catheter was removed
      postoperative day 1. If unable to void within 3 hours, participants were
      randomized into a control group and an intervention group. At scheduled
      intervals, the control group consumed 8 oz of warm water and the intervention
      group consumed 8 oz of caffeinated coffee. RESULTS: Thirty subjects were
      randomized; 14 were randomized to the water group and 16 to the caffeine group.
      Twenty-four subjects spontaneously voided after ingestion of fluid and six
      required straight catheterization. Of these six, five of the subjects had
      ingested water and one subject had ingested coffee. For those who spontaneously
      voided, there was not a significant difference between the caffeine group and the
      water group. There was a significant difference between caffeine ingestion and
      the volume of the void. DISCUSSION: Findings from this study suggest that
      ingestion of caffeine after removal of an indwelling urinary catheter in the
      postoperative patient may increase the amount of voiding volumes initially,
      therefore avoiding the need for straight catheterization. To accurately assess
      this, extending the study into postoperative day 2 would allow us to evaluate
      whether lower voiding volumes lead to the need for catheterization.

PMID- 24022424
TI  - "Everyday ethics" in the care of hospitalized older adults.
AB  - As the U.S. population ages, the proportion of hospitalized patients older than
      65 years will continue to increase with a significant number likely to have some
      degree of cognitive impairment. Because of the high rate of falls-related
      traumatic injury among older adults, many will require orthopaedic services.
      These patients may have multiple comorbidities and are at increased risk for
      complications. Varying degrees of cognitive impairment in combination with
      possible postoperative complications including delirium places these patients at
      risk for decreased decisional capacity and can create ethical dilemmas during the
      provision of bedside care. This article explores some everyday ethical dilemmas
      that nurses face in their care of hospitalized older adults, and offers nurses
      strategies to preserve patient dignity and self-determination while providing
      high-quality, evidence-based nursing care. 

PMID- 24022426
TI  - Lisinopril protects against the adriamycin nephropathy and reverses the renalase
      reduction: potential role of renalase in adriamycin nephropathy.
AB  - AIMS: To investigate the potential role of renalase in adriamycin nephropathy and
      the effect of lisinopril on the regulation of renalase. METHODS: Adriamycin
      nephropathy was induced in male Wistar rats (n=12) by a single injection of
      adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to a model
      group or a treatment group, to which were administered distilled water or the
      angiotensin converting enzyme inhibitor lisinopril, respectively, for 12 weeks.
      Six normal rats served as controls. At the end of study, physiological parameters
      and systolic blood pressure were measured. Glomerulosclerosis and
      tubulointerstitial injury were assessed by histopathology Renalase protein
      expression in kidney was quantified by immunohistochemistry and immunoblotting.
      The serum concentration and urinary excretion of renalase were determined by
      enzyme-linked immunosorbent assay. RESULTS: In model group rats, proteinuria and
      systolic blood pressure were elevated. Increased serum renalase concentration was
      observed; however, renalase protein expression in the kidney was significantly
      decreased. Compared with the model group, decreased proteinuria, lower systolic
      blood pressure, and fewer morphologic lesions were detected in the treatment
      group. Although levels of serum renalase were similar, accumulation of renalase
      in urine and kidney tissue increased notably in the treatment group compared with
      the model group. CONCLUSIONS: This study suggests that renalase may be involved
      in the process of adriamycin-induced renal injuries. Lisinopril may attenuate
      adriamycin-induced kidney injury by controlling blood pressure, which may be
      partially attributed to the renalase expression and secretion.

PMID- 24022427
TI  - A glioblastoma neurosphere line with alternative lengthening of telomeres.

PMID- 24022428
TI  - HMG CoA reductase inhibitors (statins) for dialysis patients.
AB  - BACKGROUND: People with advanced kidney disease treated with dialysis experience
      mortality rates from cardiovascular disease that are substantially higher than
      for the general population. Studies that have assessed the benefits of statins
      (HMG CoA reductase inhibitors) report conflicting conclusions for people on
      dialysis and existing meta-analyses have not had sufficient power to determine
      whether the effects of statins vary with severity of kidney disease. Recently,
      additional data for the effects of statins in dialysis patients have become
      available. This is an update of a review first published in 2004 and last updated
      in 2009. OBJECTIVES: To assess the benefits and harms of statin use in adults who
      require dialysis (haemodialysis or peritoneal dialysis). SEARCH METHODS: We
      searched the Cochrane Renal Group's Specialised Register to 29 February 2012
      through contact with the Trials' Search Co-ordinator using search terms relevant
      to this review. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi
      RCTs that compared the effects of statins with placebo, no treatment, standard
      care or other statins on mortality, cardiovascular events and treatment-related
      toxicity in adults treated with dialysis were sought for inclusion. DATA
      COLLECTION AND ANALYSIS: Two or more authors independently extracted data and
      assessed study risk of bias. Treatment effects were summarised using a random
      effects model and subgroup analyses were conducted to explore sources of
      heterogeneity. Treatment effects were expressed as mean difference (MD) for
      continuous outcomes and risk ratios (RR) for dichotomous outcomes together with
      95% confidence intervals (CI). MAIN RESULTS: The risk of bias was high in many of
      the included studies. Random sequence generation and allocation concealment was
      reported in three (12%) and four studies (16%), respectively. Participants and
      personnel were blinded in 13 studies (52%), and outcome assessors were blinded in
      five studies (20%). Complete outcome reporting occurred in nine studies (36%).
      Adverse events were only reported in nine studies (36%); 11 studies (44%)
      reported industry funding.We included 25 studies (8289 participants) in this
      latest update; 23 studies (24 comparisons, 8166 participants) compared statins
      with placebo or no treatment, and two studies (123 participants) compared statins
      directly with one or more other statins. Statins had little or no effect on major
      cardiovascular events (4 studies, 7084 participants: RR 0.95, 95% CI 0.88 to
      1.03), all-cause mortality (13 studies, 4705 participants: RR 0.96, 95% CI 0.90
      to 1.02), cardiovascular mortality (13 studies, 4627 participants: RR 0.94, 95%
      CI 0.84 to 1.06) and myocardial infarction (3 studies, 4047 participants: RR
      0.87, 95% CI 0.71 to 1.07); and uncertain effects on stroke (2 studies, 4018
      participants: RR 1.29, 95% CI 0.96 to 1.72).Risks of adverse events from statin
      therapy were uncertain; these included effects on elevated creatine kinase (5
      studies, 3067 participants: RR 1.25, 95% CI 0.55 to 2.83) or liver function
      enzymes (4 studies, 3044 participants; RR 1.09, 95% CI 0.41 to 1.25), withdrawal
      due to adverse events (9 studies, 1832 participants: RR 1.04, 95% CI 0.87 to
      1.25) or cancer (2 studies, 4012 participants: RR 0.90, 95% CI 0.72 to 1.11).
      Statins reduced total serum cholesterol (14 studies, 1803 participants; MD -44.86
      mg/dL, 95% CI -55.19 to -34.53) and low-density lipoprotein cholesterol (12
      studies, 1747 participants: MD -39.99 mg/dL, 95% CI -52.46 to -27.52) levels.
      Data comparing statin therapy directly with another statin were sparse. AUTHORS'
      CONCLUSIONS: Statins have little or no beneficial effects on mortality or
      cardiovascular events and uncertain adverse effects in adults treated with
      dialysis despite clinically relevant reductions in serum cholesterol levels.

PMID- 24022429
TI  - Validation of the Rowland Universal Dementia Assessment Scale for multicultural
      screening in Danish memory clinics.
AB  - BACKGROUND/AIMS: The Rowland Universal Dementia Assessment Scale (RUDAS) is a
      brief cognitive screening test that was developed to detect dementia in
      multicultural populations. The RUDAS has not previously been validated in
      multicultural populations outside of Australia. The aim of this study was to
      evaluate the diagnostic accuracy of the RUDAS in a multicultural sample of
      patients referred to Danish memory clinics. METHODS: Data were collected from 137
      consecutive patients (34 with an immigrant background) in three Danish memory
      clinics. All patients were given the RUDAS as a supplement to the standard
      diagnostic workup. RESULTS: Diagnostic accuracy for the RUDAS [area under the
      curve (AUC) = 0.838] was similar to that of the Mini-Mental State Examination
      (MMSE; AUC = 0.840). The cutoff score with the best balance of sensitivity,
      specificity and accuracy was <24/30 for the RUDAS (sensitivity 0.69, specificity
      0.80) and <25/30 for the MMSE (sensitivity 0.76, specificity 0.83). In contrast
      to the MMSE, regression analyses revealed that the RUDAS was unaffected by
      factors related to the patients' immigrant backgrounds. CONCLUSION: The RUDAS
      showed high specificity and proved to be less affected by cultural and linguistic
      factors than the MMSE, making it a particularly valuable tool when screening for
      cognitive impairment in elderly multicultural patient populations.

PMID- 24022430
TI  - The death of an American President and the birth of an organization: the American
      Surgical Association and its legacy.

PMID- 24022432
TI  - Comparison of outcomes for open abdominal aortic aneurysm repair and endovascular
      repair in patients with chronic renal insufficiency.
AB  - OBJECTIVE: This study investigates whether this practice is supported by
      multicenter prospectively collected data. BACKGROUND: Currently, open abdominal
      aortic aneurysm (AAA) repair (OPEN) is preferred over endovascular repair (EVAR)
      in patients with chronic renal insufficiency because of the concern that the
      contrast load used for EVAR may result in postoperative dialysis. METHODS:
      Patients who underwent EVAR and OPEN for infrarenal AAA were identified in the
      NSQIP database from 2005 to 2010. Preoperative renal function was assessed by
      estimated glomerular filtration rate (eGFR) calculated by the Chronic Kidney
      Disease Epidemiology Collaboration equation. Patients with chronic renal
      insufficiency were further stratified into 2 different groups: moderate (eGFR =
      30-60 mL/min) and severe (eGFR <30 mL/min) renal dysfunction. Multivariate
      regression model was used for data analysis. RESULTS: We identified 13,191
      patients who underwent AAA repair: 9877 patients underwent EVAR and 3314
      underwent OPEN. Forty percent of patients had eGFR of less than 60 mL/min. OPEN
      in patients with moderate renal dysfunction resulted in significantly higher
      mortality, cardiovascular events, and combined outcomes. However, in patients
      with severe renal dysfunction, these outcomes were similarly high in both OPEN
      and EVAR. Most importantly, OPEN in patients with moderate renal dysfunction
      resulted in 5.2 times higher risk of dialysis. CONCLUSIONS: Contrary to current
      practice, and despite the use of contrast, EVAR should be the first choice in
      patients with moderate renal dysfunction if they have the appropriate anatomy.
      Higher threshold for AAA repair with either OPEN or EVAR should be applied in
      patients with severe renal dysfunction because postoperative complications were
      significantly high with either approach.

PMID- 24022431
TI  - Acute cholecystitis: early versus delayed cholecystectomy, a multicenter
      randomized trial (ACDC study, NCT00447304).
AB  - OBJECTIVE: Acute cholecystitis is a common disease, and laparoscopic surgery is
      the standard of care. BACKGROUND: Optimal timing of surgery for acute
      cholecystitis remains controversial: either early surgery shortly after hospital
      admission or delayed elective surgery after a conservative treatment with
      antibiotics. METHODS: The ACDC ("Acute Cholecystitis-early laparoscopic surgery
      versus antibiotic therapy and Delayed elective Cholecystectomy") study is a
      randomized, prospective, open-label, parallel group trial. Patients were randomly
      assigned to receive immediate surgery within 24 hours of hospital admission
      (group ILC) or initial antibiotic treatment, followed by delayed laparoscopic
      cholecystectomy at days 7 to 45 (group DLC). For infection, all patients were
      treated with moxifloxacin for at least 48 hours. Primary endpoint was occurrence
      of predefined relevant morbidity within 75 days. Secondary endpoints were as
      follows: (1) 75-day morbidity using a scoring system; (2) conversion rate; (3)
      change of antibiotic therapy; (4) mortality; (5) costs; and (6) length of
      hospital stay. RESULTS: Morbidity rate was significantly lower in group ILC (304
      patients) than in group DLC (314 patients): 11.8% versus 34.4%. Conversion rate
      to open surgery and mortality did not differ significantly between groups. Mean
      length of hospital stay (5.4 days vs 10.0 days; P < 0.001) and total hospital
      costs (?2919 vs ?4262; P < 0.001) were significantly lower in group ILC.
      CONCLUSIONS: In this large, randomized trial, laparoscopic cholecystectomy within
      24 hours of hospital admission was shown to be superior to the conservative
      approach concerning morbidity and costs. Therefore, we believe that immediate
      laparoscopic cholecystectomy should become therapy of choice for acute
      cholecystitis in operable patients. (NCT00447304).

PMID- 24022433
TI  - A plasma microRNA panel for detection of colorectal adenomas: a step toward more
      precise screening for colorectal cancer.
AB  - OBJECTIVE: The main objective of this study was to investigate the potential use
      of circulating microRNAs (miRNAs) as biomarkers of colorectal (CR) adenomas.
      BACKGROUND: Detection of precancerous lesions such as CR adenoma is a key to
      reduce CR cancer (CRC) mortality. There is a great need for accurate, noninvasive
      biomarkers for detection of CR adenoma and CRC. MiRNAs are non-protein-coding
      RNAs that regulate gene expression. Our prior work investigated the dysregulation
      of 5 plasma miRNAs in CRC patients. As intended, we undertook a more
      comprehensive plasma-miRNA screening study in patients with CR adenoma and CRC.
      METHODS: We screened for 380 plasma-miRNAs using microfluidic array technology
      (Applied BioSystems) in a screening cohort of 12 healthy controls, 9 patients
      with CR adenomas, and 20 patients with CRC. A panel of the most dysregulated
      miRNAs (P < 0.05, False Discovery Rate: 5%) was then validated in a blinded
      cohort of 26 healthy controls, 16 patients with large adenomas, and 45 patients
      with CRC. RESULTS: A panel of 8 plasma miRNAs (miR-532-3p, miR-331, miR-195, miR
      17, miR-142-3p, miR-15b, miR-532, and miR-652) distinguished polyps from controls
      with high accuracy [area under curve (AUC) = 0.868 (95% confidence interval [CI]:
      0.76-0.98)]. In addition, a panel of 3 plasma miRNAs (miR-431, miR-15b, and miR
      139-3p) distinguished Stage IV CRC from controls with an [AUC = 0.896 (95% CI:
      0.78-1.0)]. Receiver-operating-characteristic curves of miRNA panels for all CRC
      versus controls and polyps versus all CRC showed AUC values of 0.829 (95% CI:
      0.73-0.93) and 0.856 (95% CI: 0.75-0.97), respectively. CONCLUSIONS: Plasma
      miRNAs are reliable, noninvasive, and inexpensive markers for CR adenomas. This
      miRNA panel warrants study in larger cohorts. Plasma-based assays could provide
      better screening compliance compared to fecal occult blood or endoscopic
      screening.

PMID- 24022434
TI  - The evolution of liver transplantation during 3 decades: analysis of 5347
      consecutive liver transplants at a single center.
AB  - OBJECTIVE: To analyze a 28-year single-center experience with orthotopic liver
      transplantation (OLT) for patients with irreversible liver failure. BACKGROUND:
      The implementation of the model for end-stage liver disease (MELD) in 2002
      represented a fundamental shift in liver donor allocation to recipients with the
      highest acuity, raising concerns about posttransplant outcome and morbidity.
      METHODS: Outcomes and factors affecting survival were analyzed in 5347
      consecutive OLTs performed in 3752 adults and 822 children between 1984 and 2012,
      including comparisons of recipient and donor characteristics, graft and patient
      outcomes, and postoperative morbidity before (n = 3218) and after (n = 2129)
      implementation of the MELD allocation system. Independent predictors of survival
      were identified. RESULTS: Overall, 1-, 5-, 10-, and 20-year patient and graft
      survival estimates were 82%, 70%, 63%, 52%, and 73%, 61%, 54%, 43%, respectively.
      Recipient survival was best in children with biliary atresia and worst in adults
      with malignancy. Post-MELD era recipients were older (54 vs 49, P < 0.001), more
      likely to be hospitalized (50% vs 47%, P = 0.026) and receiving pretransplant
      renal replacement therapy (34% vs 12%, P < 0.001), and had significantly greater
      laboratory MELD scores (28 vs 19, P < 0.001), longer wait-list times (270 days vs
      186 days, P < 0.001), and pretransplant hospital stays (10 days vs 8 days, P <
      0.001). Despite increased acuity, post-MELD era recipients achieved superior 1-,
      5-, and 10-year patient survival (82%, 70%, and 65% vs 77%, 66%, and 58%, P <
      0.001) and graft survival (78%, 66%, and 61% vs 69%, 58%, and 51%, P < 0.001)
      compared with pre-MELD recipients. Of 17 recipient and donor variables, era of
      transplantation, etiology of liver disease, recipient and donor age, prior
      transplantation, MELD score, hospitalization at time of OLT, and cold and warm
      ischemia time were independent predictors of survival. CONCLUSIONS: We present
      the world's largest reported single-institution experience with OLT. Despite
      increasing acuity in post-MELD era recipients, patient and graft survival
      continues to improve, justifying the "sickest first" allocation approach.

PMID- 24022435
TI  - Assessing readmission after general, vascular, and thoracic surgery using ACS
      NSQIP.
AB  - OBJECTIVE: In 2012, Medicare began cutting reimbursement for hospitals with high
      readmission rates. We sought to define the incidence and risk factors associated
      with readmission after surgery. METHODS: A total of 230,864 patients discharged
      after general, upper gastrointestinal (GI), small and large intestine,
      hepatopancreatobiliary (HPB), vascular, and thoracic surgery were identified
      using the 2011 American College of Surgeons National Surgical Quality Improvement
      Program. Readmission rates and patient characteristics were analyzed. A
      predictive model for readmission was developed among patients with length of stay
      (LOS) 10 days or fewer and then validated using separate samples. RESULTS: Median
      patient age was 56 years; 43% were male, and median American Society of
      Anesthesiologists (ASA) class was 2 (general surgery: 2; upper GI: 3; small and
      large intestine: 2; HPB: 3; vascular: 3; thoracic: 3; P < 0.001). The median LOS
      was 1 day (general surgery: 0; upper GI: 2; small and large intestine: 5; HPB: 6;
      vascular: 2; thoracic: 4; P < 0.001). Overall 30-day readmission was 7.8%
      (general surgery: 5.0%; upper GI: 6.9%; small and large intestine: 12.6%; HPB:
      15.8%; vascular: 11.9%; thoracic: 11.1%; P < 0.001). Factors strongly associated
      with readmission included ASA class, albumin less than 3.5, diabetes, inpatient
      complications, nonelective surgery, discharge to a facility, and the LOS (all P <
      0.001). On multivariate analysis, ASA class and the LOS remained most strongly
      associated with readmission. A simple integer-based score using ASA class and the
      LOS predicted risk of readmission (area under the receiver operator curve 0.702).
      CONCLUSIONS: Readmission among patients with the LOS 10 days or fewer occurs at
      an incidence of at least 5% to 16% across surgical subspecialties. A scoring
      system on the basis of ASA class and the LOS may help stratify readmission risk
      to target interventions.

PMID- 24022436
TI  - General surgery residency inadequately prepares trainees for fellowship: results
      of a survey of fellowship program directors.
AB  - OBJECTIVE: To assess readiness of general surgery graduate trainees entering
      accredited surgical subspecialty fellowships in North America. METHODS: A
      multidomain, global assessment survey designed by the Fellowship Council research
      committee was electronically sent to all subspecialty program directors.
      Respondents spanned minimally invasive surgery, bariatric, colorectal,
      hepatobiliary, and thoracic specialties. There were 46 quantitative questions
      distributed across 5 domains and 1 or more reflective qualitative
      questions/domains. RESULTS: There was a 63% response rate (n = 91/145). Of
      respondent program directors, 21% felt that new fellows arrived unprepared for
      the operating room, 38% demonstrated lack of patient ownership, 30% could not
      independently perform a laparoscopic cholecystectomy, and 66% were deemed unable
      to operate for 30 unsupervised minutes of a major procedure. With regard to
      laparoscopic skills, 30% could not atraumatically manipulate tissue, 26% could
      not recognize anatomical planes, and 56% could not suture. Furthermore, 28% of
      fellows were not familiar with therapeutic options and 24% were unable to
      recognize early signs of complications. Finally, it was felt that the majority of
      new fellows were unable to conceive, design, and conduct research/academic
      projects. Thematic clustering of qualitative data revealed deficits in domains of
      operative autonomy, progressive responsibility, longitudinal follow-up, and
      scholarly focus after general surgery education.

PMID- 24022437
TI  - A decade analysis of trends and outcomes of partial versus total esophagectomy in
      the United States.
AB  - OBJECTIVE: To examine the trends and outcomes of partial esophagectomy with an
      intrathoracic anastomosis compared with total esophagectomy with a cervical
      anastomosis. BACKGROUND: Controversy exists regarding the optimal surgical
      approach in the management of esophageal cancer. METHODS: Using the Nationwide
      Inpatient Sample database, yearly trends of patients with esophageal cancer who
      underwent partial and total esophagectomy were analyzed. Multivariate logistic
      regression analysis was used to analyze serious morbidity and in-hospital
      mortality between partial and total esophagectomy. In addition, outcomes were
      analyzed according to hospital volume, with low-volume centers defined as those
      with fewer than 10 cases per year and high-volume centers as those with 10 or
      more cases per year. RESULTS: Between 2001 and 2010, 15,190 esophagectomies were
      performed for cancer. There was an overall increase in the number of
      esophagectomy procedures performed (1402 to 1975), with a concomitant reduction
      in the mortality rate (8.3% to 4.2%), particularly for partial esophagectomy.
      Partial esophagectomy was the predominant operation (76%). Most operations were
      performed at low-volume centers (62%), with a recent shift of cases to high
      volume center. Compared with total esophagectomy, partial esophagectomy was
      associated with a shorter length of hospital stay (16 +/- 6 vs 19 +/- 9 days; P <
      0.05), a lower in-hospital mortality rate (5.8% vs 8.3%; P < 0.05), and a lower
      hospital charge ($119,339 vs $138,496; P < 0.05). On multivariate regression
      analysis, total esophagectomy was associated with higher serious morbidity (odds
      ratio, 1.39; P < 0.01) and in-hospital mortality (odds ratio, 1.67; P = 0.03).
      There were no significant differences in risk-adjusted outcomes between low
      volume centers and high-volume center. CONCLUSIONS: The number of esophagectomies
      performed for esophageal cancer has increased over the past decade accompanied by
      an overall reduction in mortality, particularly for the partial esophagectomy
      approach. The predominant operation in the United States continues to be partial
      esophagectomy with an intrathoracic anastomosis, which was associated with lower
      morbidity and in-hospital mortality than total esophagectomy. Hospital volume at
      a threshold of 10 cases per year was not a predictor of outcome.

PMID- 24022438
TI  - Early operation is associated with a survival benefit for patients with adhesive
      bowel obstruction.
AB  - OBJECTIVE: To evaluate the effect of surgical delay on the outcomes of patients
      with adhesive small bowel obstruction (ASBO). BACKGROUND: It is generally
      accepted that patients with uncomplicated ASBO failing nonoperative management
      should be operated on within 5 days. However, the optimal time of operation
      within this 5-day period is unknown. METHODS: Patients requiring surgery for ASBO
      were identified from the National Surgical Quality Improvement Program database.
      Linear regression was performed to evaluate the impact of incremental surgical
      delay in mortality and complications. The study population was stratified by time
      to intervention (24-hour intervals), and logistic regression was performed to
      adjust for premorbid conditions and presentation physiology. The outcomes
      included 30-day mortality and infectious complications. RESULTS: A total of 4163
      patients underwent laparotomy for ASBO. Mortality and complications increased
      significantly with operative delay. Delay of 24 hours or more was associated with
      significantly higher mortality: 6.5% vs 3.0%; adjusted odds ratio (AOR) [95%
      confidence interval (CI), 1.58 (1.12-2.24)]; P = 0.009. The delayed operation
      group (>=24 hours) also had significantly higher rates of surgical site
      infections [12.9% vs 10.0%; AOR (95% CI), 1.33 (1.08-1.62); P = 0.007], pneumonia
      (7.9% vs 5.2%; AOR (95% CI), 1.36 (1.04-1.78); P = 0.025], sepsis [7.6% vs 5.1%;
      AOR (95% CI), 1.45 (1.10-1.90); P = 0.007], and septic shock [6.2% vs 3.5%; AOR
      (95% CI), 1.47 (1.07-2.02); P = 0.018]. Early operation was associated with
      significantly shorter hospital stay [8.4 +/- 8.3 vs 14.4+/-13.5 days; adjusted
      mean difference (95% CI), -5.2 (-5.9 to -4.4); P<0.001]. CONCLUSIONS: Early
      operative intervention for patients with ASBO is associated with a significant
      survival benefit, lower incidence of local and systemic complications, and
      shorter hospitalization.

PMID- 24022439
TI  - Branch duct intraductal papillary mucinous neoplasms: does cyst size change the
      tip of the scale? A critical analysis of the revised international consensus
      guidelines in a large single-institutional series.
AB  - OBJECTIVE: The aim of this study was to critically analyze the safety of the
      revised guidelines, with focus on cyst size and worrisome features in the
      management of BD-IPMN. BACKGROUND: The Sendai guidelines for management of branch
      duct (BD) intraductal papillary mucinous neoplasm (IPMN) espouse safety of
      observation of asymptomatic cysts smaller than 3 cm without nodules (Sendai
      negative). Revised international consensus guidelines published in 2012 suggest a
      still more conservative approach, even for lesions of 3 cm or larger. By
      contrast, 2 recent studies have challenged the safety of both guidelines,
      describing invasive carcinoma or carcinoma in situ in 67% of BD-IPMN smaller than
      3 cm and in 25% of "Sendai-negative" BD-IPMN. METHODS AND RESULTS: Review of a
      prospective database identified 563 patients with BD-IPMN. A total of 240
      patients underwent surgical resection (152 at the time of diagnosis and 88 after
      being initially followed); the remaining 323 have been managed by observation
      with median follow-up of 60 months. No patient developed unresectable BD-IPMN
      carcinoma during follow-up. Invasive cancer arising in BD-IPMN was found in 23
      patients of the entire cohort (4%), and an additional 21 patients (3.7%) had or
      developed concurrent pancreatic ductal adenocarcinoma. According to the revised
      guidelines, 76% of resected BD-IPMN with carcinoma in situ and 95% of resected BD
      IPMN with invasive cancer had high-risk stigmata or worrisome features. The risk
      of high-grade dysplasia in nonworrisome lesions smaller than 3 cm was 6.5%, but
      when the threshold was raised to greater than 3 cm, it was 8.8%, and 1 case of
      invasive carcinoma was found. CONCLUSIONS: Expectant management of BD-IPMN
      following the old guidelines is safe, whereas caution is advised for larger
      lesions, even in the absence of worrisome features.

PMID- 24022440
TI  - The comparative effectiveness of surgeons over interventionalists in endovascular
      repairs of abdominal aortic aneurysm.
AB  - OBJECTIVE: Comparative effectiveness research has mostly been focused on
      comparison of treatment techniques. The goal of the present study was to extend
      the research to physician specialty. BACKGROUND: Both surgeons and
      interventionalists (cardiologists and radiologists) are involved in endovascular
      repairs (EVAR) of aortic aneurysms, with different residency education, operative
      experience, preoperative assessment and patient selection, and postoperative
      continuity of care. METHODS: Retrospective analysis was performed using the
      Nationwide Inpatient Sample from 1998 to 2009. Patients undergoing EVAR for
      abdominal aortic aneurysm were identified with International Classification of
      Diseases, Ninth Revision, procedure code 39.71. Using physician identifiers
      available in the database, surgeons were identified by case experience in the
      same calendar year with elective open AAA repairs, arteriovenous fistula repairs,
      or carotid endarderectomy. Multivariate analysis adjusted for physician volume,
      AAA ruptured status, patient demographic and comorbidities, and hospital
      characteristics. RESULTS: A total of 28,094 EVARs were analyzed. Unadjusted
      mortality rates, length of stay, and total hospital charges were significantly
      higher for patients treated by interventionalists than those by surgeons (all Ps
      < 0.001). This difference persisted on multivariate analysis, where
      interventionalists were associated with increased likelihood of mortality (odds
      ratio = 1.39; 95% confidence interval, 1.04-1.89), longer length of stay (1.32
      days; 95% confidence interval, 1.03-1.62), and higher total hospital charges
      ($19,312; 95% confidence interval, 16,471-22,153). CONCLUSIONS: Physician
      specialty is associated with patient outcomes. Surgeons are associated with
      improved outcomes, with lower mortality, shorter length of stay, and lower
      charges for EVAR cases, when compared with interventionalists. This finding has
      significant implications for future comparative effectiveness research and
      potential policy changes in patient referrals or physician admitting privileges.

PMID- 24022441
TI  - Improved outcomes of bile duct injuries in the 21st century.
AB  - OBJECTIVE: The objectives of this analysis were to compare the outcomes of bile
      duct injuries by specialist over time and the role of management timing and
      biliary stents. BACKGROUND: Postoperative bile duct injuries require
      multidisciplinary management. In recent years, advancements have occurred in
      patient evaluation and in timing and type of therapy. METHODS: A
      multidisciplinary team managed 528 patients over 18 years. Mean age was 52 years;
      69% were women and 95% had a cholecystectomy and/or bile duct exploration.
      Patients were classified by the Strasberg system as having bile leaks (type A, n
      = 239, 45%) or bile duct injuries (types B-E, n = 289, 55%). Injury outcomes from
      1993 to 2003 (n = 132) were compared with those from 2004 to 2010 (n = 157). A
      successful outcome was defined as no need for further intervention after the
      initial 12 months of therapy. Standard statistical methods were employed.
      RESULTS: Patients with bile leaks were managed almost exclusively by endoscopists
      (96%) with a 96% success rate. Patients with bile duct injuries were managed most
      often by endoscopists (N = 115, 40%) followed by surgeons (N = 104, 36%) and
      interventional radiologists (N = 70, 24%). Overall success rates were best for
      surgery (88%, P < 0.05) followed by endoscopy (76%) and interventional radiology
      (50%) and improved over time (78% vs 69%). Outcomes were best for surgery in
      recent years (95% vs 80%, P < 0.05) and for patients stented for more than 6
      months (P < 0.01). CONCLUSIONS: Almost all bile leaks and many bile duct injuries
      can be managed successfully by endoscopists. Selected proximal injuries can be
      treated by interventional radiologists with modest success. Outcomes of bile duct
      injuries are best with surgical management and in patients who are stented for
      more than 6 months.

PMID- 24022442
TI  - The influence of histopathologic tumor viability on long-term survival and
      recurrence rates following neoadjuvant therapy for esophageal adenocarcinoma.
AB  - OBJECTIVE: Our aim was to validate the effect of histopathologic tumor viability
      (HTV) on extended survival outcomes and assess the prognostic ability of the
      current staging system in patients receiving preoperative chemoradiotherapy
      (CRT). BACKGROUND: The American Joint Committee on Cancer, 7th Edition,
      esophageal carcinoma staging system is derived from patients treated with surgery
      alone and does not account for the treatment effect of CRT. The extent of HTV
      after CRT is based on response to neoadjuvant therapy and has been shown to
      correlate with patient outcome. METHODS: Medical records of 1278 patients who
      underwent esophagectomy (1990-2011) were reviewed; 784 patients underwent
      preoperative CRT. Histologic tumor viability was assessed in 602 patients and
      classified as 0% to 10%, 11% to 50%, and more than 50%. Survival was estimated
      using the Kaplan-Meier method at potential median follow-up of 67 months.
      Univariate and multivariate analyses identified variables associated with
      survival. RESULTS: Multivariate analysis identified HTV of greater than 50% (P <
      0.001, HR 2.5), positive pathologic nodal status (P < 0.001, HR 1.6), and
      positive clinical nodal status (P = 0.002, HR 1.5) but not pathologic T status (P
      = 0.816, HR 1.2) to be independently associated with survival. Actuarial 5- and
      10-year survival was 52% and 43% (HTV of 0%-10%), 45% and 33% (HTV of 11%-50%),
      and 16% for both (HTV of >50%). The best 5-year survival 56% was achieved in N0
      patients with HTV of 0% to 10% (P = 0.056, HR 1.0), contrary to 6% observed in
      node-positive patients with HTV of greater than 50% (P < 0.001, HR 3.1). Patients
      with HTV of greater than 50% demonstrated distant recurrence more frequently than
      those with HTV of less than 50% (51% vs 33%, P = 0.010, OR: 2.2) CONCLUSIONS::
      After preoperative chemoradiation, long-term outcomes of esophageal carcinoma are
      best predicted utilizing histologic tumor viability; HTV may be a practical early
      endpoint predicting efficacy of therapy.

PMID- 24022443
TI  - Long-term results of a randomized controlled trial of a nonoperative strategy
      (watchful waiting) for men with minimally symptomatic inguinal hernias.
AB  - OBJECTIVE: To assess the long-term crossover (CO) rate in men undergoing watchful
      waiting (WW) as a primary treatment strategy for their asymptomatic or minimally
      symptomatic inguinal hernias. BACKGROUND: With an average follow-up of 3.2 years,
      a randomized controlled trial comparing WW with routine repair for male patients
      with minimally symptomatic inguinal hernias led investigators to conclude that WW
      was an acceptable option [JAMA. 2006;295(3):285-292]. We now analyze patients in
      the WW group after an additional 7 years of follow-up. METHODS: At the conclusion
      of the original study, 254 men who had been assigned to WW consented to longer
      term follow-up. These patients were contacted yearly by mail questionnaire.
      Nonresponders were contacted by phone or e-mail for additional data collection.
      RESULTS: Eighty-one of the 254 men (31.9%) crossed over to surgical repair before
      the end of the original study, December 31, 2004, with a median follow-up of 3.2
      (range: 2-4.5) years. The patients have now been followed for an additional 7
      years with a maximum follow-up of 11.5 years. The estimated cumulative CO rates
      using Kaplan-Meier analysis was 68%. Men older than 65 years crossed over at a
      considerably higher rate than younger men (79% vs 62%). The most common reason
      for CO was pain (54.1%). A total of 3 patients have required an emergency
      operation, but there has been no mortality. CONCLUSIONS: Men who present to their
      physicians because of an inguinal hernia even when minimally symptomatic should
      be counseled that although WW is a reasonable and safe strategy, symptoms will
      likely progress and an operation will be needed eventually.

PMID- 24022445
TI  - Acute Stroke Imaging Research Roadmap II.

PMID- 24022444
TI  - A platform for designing hyperpolarized magnetic resonance chemical probes.
AB  - Hyperpolarization is a highly promising technique for improving the sensitivity
      of magnetic resonance chemical probes. Here we report [(15)N,
      D(9)]trimethylphenylammonium as a platform for designing a variety of
      hyperpolarized magnetic resonance chemical probes. The platform structure shows a
      remarkably long (15)N spin-lattice relaxation value (816 s, 14.1 T) for retaining
      its hyperpolarized spin state. The extended lifetime enables the detection of the
      hyperpolarized (15)N signal of the platform for several tens of minutes and thus
      overcomes the intrinsic short analysis time of hyperpolarized probes. Versatility
      of the platform is demonstrated by applying it to three types of hyperpolarized
      chemical probes: one each for sensing calcium ions, reactive oxygen species
      (hydrogen peroxide) and enzyme activity (carboxyl esterase). All of the designed
      probes achieve high sensitivity with rapid reactions and chemical shift changes,
      which are sufficient to allow sensitive and real-time monitoring of target
      molecules by (15)N magnetic resonance.

PMID- 24022447
TI  - [Does automated weaning reduce the duration of mechanical ventilation?].

PMID- 24022448
TI  - [Crohn's disease: no advantage by azathioprine and 6-mercaptopurine].

PMID- 24022449
TI  - [Does BNP-based screening reduce cardiac events? - Triage controlled by BNP in
      general practice can be useful].

PMID- 24022450
TI  - [The broad spectrum of nephrological diseases].

PMID- 24022451
TI  - [70-year-old kidney transplant patient with anorexia and weight loss. Kaposi
      sarcoma].

PMID- 24022452
TI  - [Changing spectrum of renal disease in HIV infection].
AB  - BACKGROUND AND OBJECTIVE: Renal disease is a common complication in HIV-infected
      patients. The causes and spectrum of kidney disease among these patients is
      extensive, including HIV-related and HIV unrelated causes. Our objective was to
      assess the changes in distribution of renal disease under antiretroviral therapy
      (ART). PATIENTS AND METHODS: Retrospective analysis of all patients from the
      Frankfurt HIV Cohort (FHC) who underwent renal biopsy because of chronic,
      progressive renal disease between 1989 and 2012. Two time periods were defined:
      1989-2001 (early period) and 2000-2012 (late period). RESULTS: 69 HIV-infected
      patients, mostly Caucasian and male, underwent renal biopsy (early period: 22
      patients, late period: 47 patients). During the total observation time
      immuncomplex-mediated glomerulonephritis (26.1 %), hypertensive (20.3 %) and
      diabetic nephropathy (20.3 %) were the most frequent causes of chronic renal
      disease. HIV-associated renal diseases were predominant in the first period,
      whereas hypertensive and diabetic kidney disease accounted for almost 50 % of
      cases diagnosed in the late period. Other types of renal disease frequently
      encountered during the late period include renal AA-amyloidosis and tenofovir
      related kidney disease. CONCLUSION: The underlying pathology of renal disease in
      HIV-infected patients is highly variable and evolving. Since the introduction of
      HAART, renal disease not directly related to HIV has become the predominant
      cause, reflecting the growing burden of co-morbidities in this aging population.

PMID- 24022453
TI  - [A rare cause of edema: sporadic lymphangioleiomyomatosis].
AB  - HISTORY AND CLINICAL FINDINGS: A 45-year-old woman presented with marked edema of
      both lower extremities over 6 weeks for a nephrological work-up; she had gained 8
      kg of body weight. Voiding was asymptomatic and she had a stable diuresis. The
      patient took oestrogens for contraception over 10 years. Blood pressure was
      normotensive. Serum-creatinine was 0.8 mg/dl; a slight microalbuminuria was
      noted. Left and right ventricular systolic function were normal. DIAGNOSTIC
      FINDINGS, TREATMENT AND CLINICAL COURSE: Computed tomography of the abdomen
      revealed a hemodynamically relevant obstruction of the venous blood flow or the
      lymphatic vessels as cause for the edema of both legs. Masses of
      lymphangioleiomyomas located around the v. cava inferior were documented. Biopsy
      of the masses proved a massive proliferation of smooth muscle cells and
      epitheloid cells with an immunohistochemically typical staining. Furthermore, CT
      revealed multiple pulmonary cysts in both lungs, results which are pathognomic
      for lymphangioleiomyomatosis (LAM). In our patient, the structural impairment of
      the lungs was not substantiated clinically, i. e. she had only slight dyspnoe
      during exertion. By mild diuretic treatment with HCT and fluid control, a
      moderate regression of the edema was achieved. At present, the mTOR inhibitor
      rapamycin as antiproliferative treatment is considered to reduce the
      retroperitoneal LAM-related masses on an individual basis. CONCLUSION: LAM is a
      rare genetically determined progressive disease occurring frequently in women in
      childbearing age. LAM is characterized by a proliferation of smooth muscle cells,
      lymphangioma, renal angiomyolipoma, pulmonary cysts and progressive destruction
      of lung parenchyma. Refractory edema can result from an obstruction of the venous
      blood and lymphatic flow by lymphangioma masses located paracaval, which was the
      impressive and first clinical feature of LAM in our case report.

PMID- 24022454
TI  - [When is the right time point to start dialysis?].
AB  - The transition from CKD 5 to dialysis treatment (CKD 5 D) is characterized by a
      high mortality risk for patients with chronic kidney disease (CKD). Therefore,
      the right time to start dialysis is of special interest. While there was a trend
      towards an earlier initiation of dialysis many years ago, new studies could not
      demonstrate a benefit on survivals for patients who start dialysis in a higher
      glomerular filtration rate (GFR). Delaying the start of dialysis to a lower GFR
      is possible in CKD patients with stable conditions when close nephrological
      supervision is provided. In patients with cardiorenal syndrom and acute on
      chronic renal failure, an earlier start of dialysis might be necessary as well as
      the re-evaluation after re-compensation. In elderly patients the possibilities
      and risks of a conservative treatment without dialysis should be discussed.
      Consequently, current guidelines define the optimal time to start dialysis on the
      basis of the individual risk of the patients, clinical symptoms and underlying
      disease and not only on the GFR alone. 

PMID- 24022455
TI  - [Phosphate restriction in chronic renal failure - yes].

PMID- 24022456
TI  - [Phosphate restriction in chronic renal failure - no].

PMID- 24022457
TI  - [Allocation of donated organs for transplantation: what is fair?].

PMID- 24022458
TI  - [Exceptional dismissal of chief physician employment contract in recent case
      law].

PMID- 24022459
TI  - Spatial variability of metal bioaccumulation in estuarine killifish (Fundulus
      heteroclitus) at the Callahan mine superfund site, Brooksville, ME.
AB  - The former Callahan Mine Site in Brooksville, ME, is an open-pit, hardrock mine
      site in an intertidal system, thus providing a unique opportunity to evaluate how
      metal-enriched sediments and overlying water impact estuarine food webs. Copper,
      zinc, cadmium, and lead concentrations in sediment, whole water, and Atlantic
      killifish (Fundulus heteroclitus) were evaluated at sites in Goose Pond (GP;
      Callahan Mine Site) and at reference sites. The metal concentrations of sediment,
      water, and fish were spatially distinct and significantly greater at the mine
      site than in the reference estuary. Sediment concentrations were particularly
      elevated and were above probable effects levels for all four metals adjacent to
      the tailings pile. Even in this well-mixed system, water metal concentrations
      were significantly elevated adjacent to the tailings pile, and concentrations of
      Cu and Zn were above ambient water-quality criteria for chronic marine exposure.
      Neither organic matter in the sediment nor salinity or pH of the water explained
      the metal concentrations. Adjacent to the tailings pile, killifish metal body
      burdens were elevated and were significantly related to both sediment and aqueous
      concentrations. In conclusion, (1) the contaminated sediment and seepage from the
      tailings impoundment and waste rock pile no. 3 create a continual flux of metals
      into the water column, (2) the metals are bioavailable and bioconcentrating as
      evident in the killifish tissue concentrations, and (3) Callahan Mine is directly
      affecting metal bioaccumulation in fauna residing in the GP estuary and,
      potentially, in Penobscot Bay by the way of "trophic nekton relay."

PMID- 24022460
TI  - Increased ion conductance across mammalian membranes modified with conjugated
      oligoelectrolytes.
AB  - Variation in conjugated oligoelectrolyte (COE) repeat units is shown to affect
      the rate of COE insertion into mammalian membrane patches and membrane patch
      stabilities. These findings suggest that it is possible to find COE structures
      that do not destroy membranes while at the same time allow for more facile
      transmembrane movement of ions/substrates. 

PMID- 24022461
TI  - A quantitative assay to study protein:DNA interactions, discover transcriptional
      regulators of gene expression, and identify novel anti-tumor agents.
AB  - Many DNA-binding assays such as electrophoretic mobility shift assays (EMSA),
      chemiluminescent assays, chromatin immunoprecipitation (ChIP)-based assays, and
      multiwell-based assays are used to measure transcription factor activity.
      However, these assays are nonquantitative, lack specificity, may involve the use
      of radiolabeled oligonucleotides, and may not be adaptable for the screening of
      inhibitors of DNA binding. On the other hand, using a quantitative DNA-binding
      enzyme-linked immunosorbent assay (D-ELISA) assay, we demonstrate nuclear protein
      interactions with DNA using the RUNX2 transcription factor that depend on
      specific association with consensus DNA-binding sequences present on biotin
      labeled oligonucleotides. Preparation of cells, extraction of nuclear protein,
      and design of double stranded oligonucleotides are described. Avidin-coated 96
      well plates are fixed with alkaline buffer and incubated with nuclear proteins in
      nucleotide blocking buffer. Following extensive washing of the plates, specific
      primary antibody and secondary antibody incubations are followed by the addition
      of horseradish peroxidase substrate and development of the colorimetric reaction.
      Stop reaction mode or continuous kinetic monitoring were used to quantitatively
      measure protein interaction with DNA. We discuss appropriate specificity
      controls, including treatment with non-specific IgG or without protein or primary
      antibody. Applications of the assay are described including its utility in drug
      screening and representative positive and negative results are discussed. 

PMID- 24022462
TI  - An improved AMBER force field for alpha,alpha-dialkylated peptides: intrinsic and
      solvent-induced conformational preferences of model systems.
AB  - alpha,alpha-Dialkylated amino acid residues have acquired considerable importance
      as effective means for introducing backbone conformation constraints in synthetic
      peptides. The prototype of such a class of residues, namely Aib (alpha
      aminoisobutyric acid), appears to play a dominant role in determining the
      preferred conformations of host proteins. We have recently introduced into the
      standard AMBER force field some new parameters, fitted against high-level quantum
      mechanical (QM) data, for simulating peptides containing alpha,alpha-dialkylated
      residues with cyclic side chains, such as TOAC (TOAC, 2,2,6,6
      tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) and Ac6c (Ac6c = 1
      aminocyclohexaneacetic acid). Here, we show that in order to accurately reproduce
      the observed conformational geometries and structural fluctuations of linear
      alpha,alpha-dialkylated peptides based on Aib, further improvements of the non
      bonding and side chain torsion potential parameters have to be considered, due to
      the expected larger structural flexibility of linear residues with respect to
      cyclic ones. To this end, we present an extended set of parameters, which have
      been optimized by fitting the energies of multiple conformations of the Aib
      dipeptide analogue to corresponding QM calculations that properly account for
      dispersion interactions (B3LYP-D3). The quality, transferability and size
      consistency of the proposed force field have been assessed both by considering a
      series of poly-Aib peptides, modeled at the same QM level, and by performing
      molecular dynamics simulations in solvents with high and low polarity. As a
      result, the present parameters allow one to reproduce with good reliability the
      available QM and experimental data, thus representing a notable improvement over
      current force field especially in the description of the alpha/310-helix
      conformational equilibria of alpha,alpha-dialkylated peptides with linear and
      cyclic side chains. 

PMID- 24022463
TI  - Spontaneous intercalation of long-chain alkyl ammonium into edge-selectively
      oxidized graphite to efficiently produce high-quality graphene.
AB  - Mass production of high-quality graphene nanosheets (GNs) is essential for
      practical applications. We report that oxidation of graphite by low concentration
      KMnO4 at relatively high temperature (60  degrees C) leads to edge-selectively
      oxidized graphite (EOG) which preserves the high crystalline graphitic structure
      on its basal planes while the edges are functionalized by oxygen-containing
      groups. Long-chain tetradecyl-ammonium salt (C14N+) could be spontaneously
      intercalated into EOG to form intercalated EOG-C14N+ compounds. Gentle and short
      time sonication of EOG-C14N+ in toluene can full exfoliate EOG into edge-oxidized
      graphene nanosheets (EOGNs) with concentration of 0.67 mg/ml, monolayer
      population up to 90% and lateral size from 1 MUm to >100 MUm. The EOG and EOGN
      films show excellent electrical conductance, which is far superior to their
      graphene oxide (GO) counterparts. Our method provides an efficient way to produce
      high-quality GNs, and the resultant EOG also can be directly used for production
      of multifunctional materials and devices.

PMID- 24022466
TI  - Two-step fabrication of a porous gamma-In2Se3 tetragonal photocatalyst for water
      splitting.
AB  - A porous semiconductor photocatalyst, gamma-In2Se3, was first synthesized by a
      two-step hydrothermal-calcining process. It was shown that the porous gamma
      In2Se3 tetragons have superior photocatalytic activity for water splitting over
      gamma-In2Se3 nanoparticles and commercial counterparts, which might be attributed
      to the combined effect of stronger UV light absorption properties and a porous
      structure. 

PMID- 24022464
TI  - Cellular immune response in young children accounts for recurrent acute otitis
      media.
AB  - Acute otitis media (AOM) is a common disease in young children. Streptococcus
      pneumoniae (Spn) and Haemophilus influenzae (NTHi) are the two most common
      pathogens that cause AOM. Over the past 5 years, our group has been studying the
      immunologic profile of children that experience repeated AOM infections despite
      tympanocentesis drainage of middle ear fluid and individualized antibiotic
      treatment; we call these children stringently-defined otitis prone(sOP). Although
      protection against AOM is primarily mediated by ototpathogen-specific antibody,
      our recent studies suggest that suboptimal memory B and T cell responses and an
      immaturity in antigen-presenting cells may play a significant role in the
      propensity to recurrent AOM infections. This review focuses on the studies
      performed to define immunologic dysfunction in sOP children.

PMID- 24022465
TI  - Will sublingual immunotherapy offer benefit for asthma?
AB  - Evidence shows that sublingual immunotherapy (SLIT) is indicated in patients with
      allergic rhinitis (AR). In this article we discuss whether SLIT could offer
      benefit for children and adults with asthma.We reviewed individual trials on SLIT
      in asthmatic patients, but also asthma data reported in some SLIT trials
      conducted in AR patients. Findings were complemented with data from systematic
      reviews and metaanalysis on the subject since 2000 and some guidelines that
      mention immunotherapy for asthma treatment. In AR patients with concomitant
      persistent asthma, SLIT reduces medication needs while maintaining symptom
      control. This holds especially true for house dust mite SLIT. Data on pollen SLIT
      and lung symptom improvement with SLIT, however, are less convincing. Therefore,
      we suggest SLIT should be added as an optional add-on therapy for patients with
      asthma whenever a causative allergen has been demonstrated and AR is associated
      with asthma. For the future, SLIT should be studied in specifically designed
      asthma studies in allergic asthmatics without AR.

PMID- 24022467
TI  - COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of
      colon and rectal cancers in two independent populations.
AB  - PURPOSE: Nonsteroidal anti-inflammatory drugs (NSAIDs) target the prostaglandin H
      synthase enzymes, cyclooxygenase (COX)-1 and COX-2, and reduce colorectal cancer
      risk. Genetic variation in the genes encoding these enzymes may be associated
      with changes in colon and rectal cancer risk and in NSAID efficacy. METHODS: We
      genotyped candidate polymorphisms and tag SNPs in PTGS1 (COX-1) and PTGS2 (COX-2)
      in a population-based case-control study (Diet, Activity and Lifestyle Study,
      DALS) of colon cancer (n = 1,470 cases/1,837 controls) and rectal cancer (n =
      583/775), and independently among cases and controls from the Colon Cancer Family
      Registry (CCFR; colon n = 959/1,535, rectal n = 505/839). RESULTS: In PTGS2, a
      functional polymorphism (-765G[C; rs20417) was associated with a twofold
      increased rectal cancer risk (p = 0.05) in the DALS. This association replicated
      with a significant nearly fivefold increased risk of rectal cancer in the CCFR
      study (ORCC vs. GG = 4.88; 95 % CI 1.54-15.45; ORGC vs. GG = 1.36; 95 %CI 0.95
      1.94). Genotype-NSAID interactions were observed in the DALS for PTGS1 and rectal
      cancer risk and for PTGS2 and colon cancer risk, but were no longer significant
      after correcting for multiple comparisons and did not replicate in the CCFR. No
      significant associations between PTGS1 polymorphisms and colon or rectal cancer
      risk were observed.

PMID- 24022468
TI  - Discovery of indeno[1, 2 - c] quinoline derivatives as dual topoisomerases I/II
      inhibitors: part 3.
AB  - (E) -6-Hydroxy-9-methoxy-6-(piperazin-1-yl)-11H -indeno[1,2-c ]quinolin-11-one O
      2-(pyrrolidin-1-yl)ethyl oxime (2c) was identified as a potential dual topo I/II
      inhibitor in our previous paper. In continuation for the search of more potent
      compounds, we describe herein the preparation of certain indeno[1,2-c ]quinoline
      derivatives and evaluation of their antiproliferation, DNA binding affinity, and
      topoisomerases (topo I and topo II) inhibitory activities. Among them, (E) -9-[3
      (dimethylamino)propoxy]-11H -indeno[1,2-c ]quinolin-11-one O-3
      (dimethylamino)propyl oxime (11b) and its analog 11c exhibited approximately
      equal activity to the lead compound 2c against the growth of HeLa and A549 cancer
      cells. Both compounds 11b and 11c were more active than 2c in the inhibition of
      topo I and topo II. However, none of them exhibited significant DNA binding
      affinity while 2c was a very strong DNA binding agent. Compound 11b exhibited a
      high oral bioavailability of 39.8 % while the oral bioavailability of 2c and 11c
      was only 10.9 and 8.6 %, respectively. The in vivo anti-tumor evaluation of 11b
      in nude mice bearing subcutaneous breast cancer tumors revealed that treatment
      with low (10 mg/kg) or high (30 mg/kg) doses of 11b dramatically diminished tumor
      growth. Therefore, compound 11b is identified as a potential non-DNA
      intercalating dual topo I/II inhibitor.

PMID- 24022469
TI  - Dyadic concordance in mother and preschooler resting cardiovascular function
      varies by risk status.
AB  - This study examined concordance in heart rate (HR) and respiratory sinus
      arrhythmia (RSA) in a sample of 104 child-maltreating (CM) and nonCM mother
      preschooler dyads (208 individuals). In a laboratory setting, mother and child
      cardiac physiology was simultaneously monitored via ECG in a 5-min resting
      period. Mothers ranged in age from 20 to 49 years; children ranged in age from 3
      to 5 years. Significant within-dyad (WD) and between-dyad (BD) associations were
      observed for mother HR and both child HR and RSA, and the associations were
      moderated by CM status. Only CM dyads exhibited BD associations: Higher average
      maternal HR was associated with higher child HR and lower child RSA. By contrast,
      when the time interval was divided into 30 s epochs, nonCM dyads exhibited
      positive WD (dynamic) associations in mother and child HR, and both CM and nonCM
      dyads showed negative WD associations in mother HR and child RSA. Further,
      mothers' mean HR levels moderated the extent of epoch-by-epoch WD concordance
      observed in mother and child, such that elevated average maternal HR was
      associated with lower levels of WD (dynamic) concordance. No BD or WD concordance
      in maternal and child RSA was observed. The findings suggest that measures of
      intraindividual variation provide useful, alternate perspectives in the study of
      dyadic processes in at-risk families.

PMID- 24022470
TI  - MicroRNA-127-5p regulates matrix metalloproteinase 13 expression and interleukin
      1beta-induced catabolic effects in human chondrocytes.
AB  - OBJECTIVE: MicroRNAs (miRNAs), small noncoding RNA molecules, are involved in the
      pathogenesis of various diseases such as cancer and arthritis. The aim of this
      study was to determine whether miR-127-5p regulates interleukin-1beta (IL-1beta)
      induced expression of matrix metalloproteinase 13 (MMP-13) and other catabolic
      factors in human chondrocytes. METHODS: Expression of miR-127-5p and MMP-13 by
      normal and osteoarthritic (OA) human cartilage was determined using real-time
      polymerase chain reaction. The effect of miR-127-5p on MMP-13 expression was
      evaluated using transient transfection of human chondrocytes or chondrogenic SW
      1353 cells with miR-127-5p or its antisense inhibitor (anti-miR-127-5p). MMP-13
      protein production was quantified by enzyme-linked immunosorbent assay, and the
      involvement of miR-127-5p in IL-1beta-mediated catabolic effects was examined by
      immunoblotting. MicroRNA-127-5p binding with the putative site in the 3'
      untranslated region (3'-UTR) of MMP-13 messenger RNA (mRNA) was validated by
      luciferase reporter assay. RESULTS: There was a significant reduction in miR-127
      5p expression in OA cartilage compared with normal cartilage. Up-regulation of
      MMP-13 expression by IL-1beta was correlated with down-regulation of miR-127-5p
      expression in human chondrocytes. MicroRNA-127-5p suppressed IL-1beta-induced MMP
      13 production as well as the activity of a reporter construct containing the 3'
      UTR of human MMP-13 mRNA. In addition, mutation of the miR-127-5p binding site in
      the 3'-UTR of MMP-13 mRNA abolished miR-127-5p-mediated repression of reporter
      activity. Conversely, treatment with anti-miR-127-5p remarkably increased
      reporter activity and MMP-13 production. Interestingly, the IL-1beta-induced
      activation of JNK, p38, and NF-kappaB and expression of MMP-1 and cyclooxygenase
      2 were significantly inhibited by miR-127-5p. CONCLUSION: MicroRNA-127-5p is an
      important regulator of MMP-13 in human chondrocytes and may contribute to the
      development of OA.

PMID- 24022472
TI  - Tracing the evolution of streptophyte algae and their mitochondrial genome.
AB  - Six monophyletic groups of charophycean green algae are recognized within the
      Streptophyta. Although incongruent with earlier studies based on genes from three
      cellular compartments, chloroplast and nuclear phylogenomic analyses have
      resolved identical relationships among these groups, placing the Zygnematales or
      the Zygnematales + Coleochaetales as sister to land plants. The present
      investigation aimed at determining whether this consensus view is supported by
      the mitochondrial genome and at gaining insight into mitochondrial DNA (mtDNA)
      evolution within and across streptophyte algal lineages and during the transition
      toward the first land plants. We present here the newly sequenced mtDNAs of
      representatives of the Klebsormidiales (Entransia fimbriata and Klebsormidium
      spec.) and Zygnematales (Closterium baillyanum and Roya obtusa) and compare them
      with their homologs in other charophycean lineages as well as in selected
      embryophyte and chlorophyte lineages. Our results indicate that important changes
      occurred at the levels of genome size, gene order, and intron content within the
      Zygnematales. Although the representatives of the Klebsormidiales display more
      similarity in genome size and intron content, gene order seems more fluid and
      gene losses more frequent than in other charophycean lineages. In contrast, the
      two members of the Charales display an extremely conservative pattern of mtDNA
      evolution. Collectively, our analyses of gene order and gene content and the
      phylogenies we inferred from 40 mtDNA-encoded proteins failed to resolve the
      relationships among the Zygnematales, Coleochaetales, and Charales; however, they
      are consistent with previous phylogenomic studies in favoring that the
      morphologically complex Charales are not sister to land plants. 

PMID- 24022473
TI  - Caroli's disease.

PMID- 24022475
TI  - ARNT2 mutation causes hypopituitarism, post-natal microcephaly, visual and renal
      anomalies.
AB  - We describe a previously unreported syndrome characterized by secondary (post
      natal) microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary
      hormone deficiency, seizures, severe visual impairment and abnormalities of the
      kidneys and urinary tract in a highly consanguineous family with six affected
      children. Homozygosity mapping and exome sequencing revealed a novel homozygous
      frameshift mutation in the basic helix-loop-helix transcription factor gene ARNT2
      (c.1373_1374dupTC) in affected individuals. This mutation results in absence of
      detectable levels of ARNT2 transcript and protein from patient fibroblasts
      compared with controls, consistent with nonsense-mediated decay of the mutant
      transcript and loss of ARNT2 function. We also show expression of ARNT2 within
      the central nervous system, including the hypothalamus, as well as the renal
      tract during human embryonic development. The progressive neurological
      abnormalities, congenital hypopituitarism and post-retinal visual pathway
      dysfunction in affected individuals demonstrates for the first time the essential
      role of ARNT2 in the development of the hypothalamo-pituitary axis, post-natal
      brain growth, and visual and renal function in humans. 

PMID- 24022476
TI  - Search strategies to identify diagnostic accuracy studies in MEDLINE and EMBASE.
AB  - BACKGROUND: A systematic and extensive search for as many eligible studies as
      possible is essential in any systematic review. When searching for diagnostic
      test accuracy (DTA) studies in bibliographic databases, it is recommended that
      terms for disease (target condition) are combined with terms for the diagnostic
      test (index test). Researchers have developed methodological filters to try to
      increase the precision of these searches. These consist of text words and
      database indexing terms and would be added to the target condition and index test
      searches.Efficiently identifying reports of DTA studies presents challenges
      because the methods are often not well reported in their titles and abstracts,
      suitable indexing terms may not be available and relevant indexing terms do not
      seem to be consistently assigned. A consequence of using search filters to
      identify records for diagnostic reviews is that relevant studies might be missed,
      while the number of irrelevant studies that need to be assessed may not be
      reduced. The current guidance for Cochrane DTA reviews recommends against the
      addition of a methodological search filter to target condition and index test
      search, as the only search approach. OBJECTIVES: To systematically review
      empirical studies that report the development or evaluation, or both, of
      methodological search filters designed to retrieve DTA studies in MEDLINE and
      EMBASE. SEARCH METHODS: We searched MEDLINE (1950 to week 1 November 2012);
      EMBASE (1980 to 2012 Week 48); the Cochrane Methodology Register (Issue 3, 2012);
      ISI Web of Science (11 January 2013); PsycINFO (13 March 2013); Library and
      Information Science Abstracts (LISA) (31 May 2010); and Library, Information
      Science & Technology Abstracts (LISTA) (13 March 2013). We undertook citation
      searches on Web of Science, checked the reference lists of relevant studies, and
      searched the Search Filters Resource website of the InterTASC Information
      Specialists' Sub-Group (ISSG). SELECTION CRITERIA: Studies reporting the
      development or evaluation, or both, of a MEDLINE or EMBASE search filter aimed at
      retrieving DTA studies, which reported a measure of the filter's performance were
      eligible. DATA COLLECTION AND ANALYSIS: The main outcome was a measure of filter
      performance, such as sensitivity or precision. We extracted data on the
      identification of the reference set (including the gold standard and, if used,
      the non-gold standard records), how the reference set was used and any
      limitations, the identification and combination of the search terms in the
      filters, internal and external validity testing, the number of filters evaluated,
      the date the study was conducted, the date the searches were completed, and the
      databases and search interfaces used. Where 2 x 2 data were available on filter
      performance, we used these to calculate sensitivity, specificity, precision and
      Number Needed to Read (NNR), and 95% confidence intervals (CIs). We compared the
      performance of a filter as reported by the original development study and any
      subsequent studies that evaluated the same filter. MAIN RESULTS: Ninteen studies
      were included, reporting on 57 MEDLINE filters and 13 EMBASE filters. Thirty
      MEDLINE and four EMBASE filters were tested in an evaluation study where the
      performance of one or more filters was tested against one or more gold standards.
      The reported outcome measures varied. Some studies reported specificity as well
      as sensitivity if a reference set containing non-gold standard records in
      addition to gold standard records was used. In some cases, the original
      development study did not report any performance data on the filters. Original
      performance from the development study was not available for 17 filters that were
      subsequently tested in evaluation studies. All 19 studies reported the
      sensitivity of the filters that they developed or evaluated, nine studies
      reported the specificities and 14 studies reported the precision.No filter which
      had original performance data from its development study, and was subsequently
      tested in an evaluation study, had what we defined a priori as acceptable
      sensitivity (> 90%) and precision (> 10%). In studies that developed MEDLINE
      filters that were evaluated in another study (n = 13), the sensitivity ranged
      from 55% to 100% (median 86%) and specificity from 73% to 98% (median 95%).
      Estimates of performance were lower in eight studies that evaluated the same 13
      MEDLINE filters, with sensitivities ranging from 14% to 100% (median 73%) and
      specificities ranging from 15% to 96% (median 81%). Precision ranged from 1.1% to
      40% (median 9.5%) in studies that developed MEDLINE filters and from 0.2% to
      16.7% (median 4%) in studies that evaluated these filters. A similar range of
      specificities and precision were reported amongst the evaluation studies for
      MEDLINE filters without an original performance measure. Sensitivities ranged
      from 31% to 100% (median 71%), specificity ranged from 13% to 90% (median 55.5%)
      and precision from 1.0% to 11.0% (median 3.35%).For the EMBASE filters, the
      original sensitivities reported in two development studies ranged from 74% to
      100% (median 90%) for three filters, and precision ranged from 1.2% to 17.6%
      (median 3.7%). Evaluation studies of these filters had sensitivities from 72% to
      97% (median 86%) and precision from 1.2% to 9% (median 3.7%). The performance of
      EMBASE search filters in development and evaluation studies were more alike than
      the performance of MEDLINE filters in development and evaluation studies. None of
      the EMBASE filters in either type of study had a sensitivity above 90% and
      precision above 10%. AUTHORS' CONCLUSIONS: None of the current methodological
      filters designed to identify reports of primary DTA studies in MEDLINE or EMBASE
      combine sufficiently high sensitivity, required for systematic reviews, with a
      reasonable degree of precision. This finding supports the current recommendation
      in the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy that
      the combination of methodological filter search terms with terms for the index
      test and target condition should not be used as the only approach when conducting
      formal searches to inform systematic reviews of DTA.

PMID- 24022474
TI  - Asymmetry of planum temporale constrains interhemispheric language plasticity in
      children with focal epilepsy.
AB  - Reorganization of eloquent cortex enables rescue of language functions in
      patients who sustain brain injury. Individuals with left-sided, early-onset focal
      epilepsy often show atypical (i.e. bilateral or right-sided) language dominance.
      Surprisingly, many patients fail to show such interhemispheric shift of language
      despite having major epileptogenic lesions in close proximity to eloquent cortex.
      Although a number of epilepsy-related factors may promote interhemispheric
      plasticity, it has remained unexplored if neuroanatomical asymmetries linked to
      human language dominance modify the likelihood of atypical lateralization. Here
      we examined the asymmetry of the planum temporale, one of the most striking
      asymmetries in the human brain, in relation to language lateralization in
      children with left-sided focal epilepsy. Language functional magnetic resonance
      imaging was performed in 51 children with focal epilepsy and left-sided lesions
      and 36 healthy control subjects. We examined the association of language
      laterality with a range of potential clinical predictors and the asymmetry of the
      length of the planum temporale. Using voxel-based methods, we sought to determine
      the effect of lesion location (in the affected left hemisphere) and grey matter
      density (in the unaffected right hemisphere) on language laterality. Atypical
      language lateralization was observed in 19 patients (38%) and in four controls
      (11%). Language laterality was increasingly right-sided in patients who showed
      atypical handedness, a left perisylvian ictal electroencephalographic focus, and
      a lesion in left anterior superior temporal or inferior frontal regions. Most
      striking was the relationship between rightward asymmetry of the planum temporale
      and atypical language (R = 0.70, P < 0.0001); patients with a longer planum
      temporale in the right (unaffected) hemisphere were more likely to have atypical
      language dominance. Voxel-based regression analysis confirmed that increased grey
      matter density in the right temporo-parietal junction was correlated with right
      hemisphere lateralization of language. The length of the planum temporale in the
      right hemisphere was the main predictor of language lateralization in the
      epilepsy group, accounting for 48% of variance, with handedness accounting for
      only a further 5%. There was no correlation between language lateralization and
      planum temporale asymmetry in the control group. We conclude that asymmetry of
      the planum temporale may be unrelated to language lateralization in healthy
      individuals, but the size of the right, contra-lesional planum temporale region
      may reflect a 'reserve capacity' for interhemispheric language reorganization in
      the presence of a seizure focus and lesions within left perisylvian regions. 

PMID- 24022478
TI  - Assessment of serum level of interleukin-1b and interleukin-12 in leprosy: impact
      of previous Bacillus Calmitte Guerin vaccination.
AB  - Macrophages play an important role in attempt to eliminate mycobacteria, via
      production of cytokines, including interleukin-1, and interleukin-12. Bacillus
      Calmitte Guerin (BCG) vaccination, known to induce interleukin-1beta in
      tuberculosis, was originally aimed at tuberculosis control, but it showed
      efficacy against leprosy. Our aim was to estimate serum levels of interleukin
      1beta and interleukin-12, in leprosy, and to assess the impact of previous BCG
      vaccination on their levels. Serum interleukin-1beta and interleukin-12 p70 were
      estimated in 43 leprotic patients and 43 controls by enzyme-linked immunosorbent
      assay. Patients were grouped according to presence or absence of reactions, as
      well as bacillary load. Serum interleukin-1beta was significantly higher in
      patients as compared to controls (p = 0.047), and was significantly different in
      patients' groups (p = 0.036); with significantly higher level in multibacillary
      patients, both non reactional and with erythema nodosum leprosum, compared with
      paucibacillary/non reactional patients (p = 0.012 and 0.049 respectively). A
      statistically significant higher interleukin-1beta was found in BCG vaccinated
      paucibacillary patients as compared to unvaccinated patients (p = 0.031).
      Significantly elevated interleukin-12 was present in patients as compared to
      controls (p < 0.001), with no statistically significant difference comparing
      patients' groups. BCG vaccination showed stimulatory effect on monocytes only in
      the immunocompetent paucibacillary leprosy patients, as evidenced by higher
      Interleukin-1beta in this group. Interleukin-1beta was shown to have a pro
      inflammatory role in multibacillary patients with or without erythema nodosum
      leprosum. Targeting interleukin-1beta may be promising to control episodic
      refractory erythema nodosum leprosum. Interleukin-12 may be a general marker of
      active Mycobacterium leprae infection.

PMID- 24022477
TI  - The role of microRNAs in skin fibrosis.
AB  - Fibrotic skin disorders may be debilitating and impair quality of life. There are
      few effective treatment options for cutaneous fibrotic diseases. In this review,
      we discuss our current understanding of the role of microRNAs (miRNAs) in skin
      fibrosis. miRNAs are a class of small, non-coding RNAs involved in skin fibrosis.
      These small RNAs range from 18 to 25 nucleotides in length and modify gene
      expression by binding to target messenger RNA (mRNA), causing degradation of the
      target mRNA or inhibiting the translation into proteins. We present an overview
      of the biogenesis, maturation and function of miRNAs. We highlight miRNA's role
      in key skin fibrotic processes including: transforming growth factor-beta
      signaling, extracellular matrix deposition, and fibroblast proliferation and
      differentiation. Some miRNAs are profibrotic and their upregulation favors these
      processes contributing to fibrosis, while anti-fibrotic miRNAs inhibit these
      processes and may be reduced in fibrosis. Finally, we describe the diagnostic and
      therapeutic significance of miRNAs in the management of skin fibrosis. The
      discovery that miRNAs are detectable in serum, plasma, and other bodily fluids,
      and are relatively stable, suggests that miRNAs may serve as valuable biomarkers
      to monitor disease progression and response to treatment. In the treatment of
      skin fibrosis, antifibrotic miRNAs may be upregulated using mimics and viral
      vectors. Conversely, profibrotic miRNAs may be downregulated by employing anti
      miRNAs, sponges, erasers and masks. We believe that miRNA-based therapies hold
      promise as important treatments and may transform the management of fibrotic skin
      diseases by physicians.

PMID- 24022479
TI  - Endoplasmic reticulum oxidoreductin-1alpha (Ero1alpha) improves folding and
      secretion of mutant proinsulin and limits mutant proinsulin-induced endoplasmic
      reticulum stress.
AB  - Upon chronic up-regulation of proinsulin synthesis, misfolded proinsulin can
      accumulate in the endoplasmic reticulum (ER) of pancreatic beta-cells, promoting
      ER stress and type 2 diabetes mellitus. In Mutant Ins-gene-induced Diabetes of
      Youth (MIDY), misfolded mutant proinsulin impairs ER exit of co-expressed wild
      type proinsulin, limiting insulin production and leading to eventual beta-cell
      death. In this study we have investigated the hypothesis that increased
      expression of ER oxidoreductin-1alpha (Ero1alpha), despite its established role
      in the generation of H2O2, might nevertheless be beneficial in limiting
      proinsulin misfolding and its adverse downstream consequences. Increased
      Ero1alpha expression is effective in promoting wild-type proinsulin export from
      cells co-expressing misfolded mutant proinsulin. In addition, we find that upon
      increased Ero1alpha expression, some of the MIDY mutants themselves are directly
      rescued from ER retention. Secretory rescue of proinsulin-G(B23)V is correlated
      with improved oxidative folding of mutant proinsulin. Indeed, using three
      different variants of Ero1alpha, we find that expression of either wild-type or
      an Ero1alpha variant lacking regulatory disulfides can rescue mutant proinsulin
      G(B23)V, in parallel with its ability to provide an oxidizing environment in the
      ER lumen, whereas beneficial effects were less apparent for a redox-inactive form
      of Ero1. Increased expression of protein disulfide isomerase antagonizes the
      rescue provided by oxidatively active Ero1. Importantly, ER stress induced by
      misfolded proinsulin was limited by increased expression of Ero1alpha, suggesting
      that enhancing the oxidative folding of proinsulin may be a viable therapeutic
      strategy in the treatment of type 2 diabetes. 

PMID- 24022480
TI  - Degradation of p12 subunit by CRL4Cdt2 E3 ligase inhibits fork progression after
      DNA damage.
AB  - After acute DNA damage, the cell arrests S-phase progression by inhibiting origin
      initiation and fork progression to repair damaged DNA. The intra-S-phase
      checkpoint kinase Chk1 phosphorylates Cdc25A to target the latter for degradation
      by CRL1(beta-TrCP) and so inhibit origin firing. The mechanism for inhibiting
      fork progression, however, has not been identified. Here, we show that
      degradation of p12, the fourth subunit of DNA polymerase delta, is critical for
      inhibiting fork progression. CRL4(Cdt2) is an E3 ligase that ubiquitinates and
      degrades p12 after UV treatment. Cells expressing a stable form of p12 exhibit UV
      resistant DNA synthesis. DNA fiber assay and alkaline-sucrose gradient assay
      demonstrate that the impairment of fork progression after DNA damage requires p12
      degradation. These results suggest that ubiquitination of p12 through CRL4(Cdt2)
      and subsequent degradation form one mechanism by which a cell responds to DNA
      damage to inhibit fork progression. 

PMID- 24022481
TI  - Hepatocyte nuclear factor 6 suppresses the migration and invasive growth of lung
      cancer cells through p53 and the inhibition of epithelial-mesenchymal transition.
AB  - Epithelial-mesenchymal transition plays an important role in many patho
      physiological processes, including cancer invasion and metastatic progression.
      Hepatocyte nuclear factor 6 (HNF6) has been known to be an important factor for
      both physiological and pathological functions in liver and pancreas. However, its
      role in EMT and lung cancer progression remains unidentified. We observed that
      HNF6 level can be down-regulated by TGF-beta1 in human lung cancer cells.
      Knockdown of HNF6 induced EMT and increased cell migration. In contrast,
      ectopically expression of HNF6 inhibited cell migration and attenuated TGF-beta1
      induced EMT. The data suggest that HNF6 plays a role in maintaining epithelial
      phenotype, which suppresses EMT. HNF6 also inhibits both colony formation and
      proliferation of lung cancer cells. It pronouncedly reduced the formation of
      tumor xenografts in nude mice. In addition, HNF6 can activate the promoter
      activity of p53 by directly binding to a specific region of its promoter and
      therefore increase the protein level of tumor suppressor p53. p53 knockdown
      induced EMT and increased cell migration, whereas the opposite effect was
      generated by p53 overexpression. p53 knockdown also inhibited the effect of HNF6
      on EMT and cell migration, indicating that p53 is required for the functions of
      HNF6 herein. Moreover, there is a high positive correlation among the expression
      levels of HNF6, p53, and E-cadherin in human lung cancer cells and tissues. The
      data suggest that HNF6 inhibits EMT, cell migration, and invasive growth through
      a mechanism involving the transcriptional activation of p53. 

PMID- 24022483
TI  - Zebrafish cytosolic carboxypeptidases 1 and 5 are essential for embryonic
      development.
AB  - The cytosolic carboxypeptidases (CCPs) are a subfamily of metalloenzymes within
      the larger M14 family of carboxypeptidases that have been implicated in the post
      translational modification of tubulin. It has been suggested that at least four
      of the six mammalian CCPs function as tubulin deglutamylases. However, it is not
      yet clear whether these enzymes play redundant or unique roles within the cell.
      To address this question, genes encoding CCPs were identified in the zebrafish
      genome. Analysis by quantitative polymerase chain reaction indicated that CCP1,
      CCP2, CCP5, and CCP6 mRNAs were detectable between 2 h and 8 days
      postfertilization with highest levels 5-8 days postfertilization. CCP1, CCP2, and
      CCP5 mRNAs were predominantly expressed in tissues such as the brain, olfactory
      placodes, and pronephric ducts. Morpholino oligonucleotide-mediated knockdown of
      CCP1 and CCP5 mRNA resulted in a common phenotype including ventral body
      curvature and hydrocephalus. Confocal microscopy of morphant zebrafish revealed
      olfactory placodes with defective morphology as well as pronephric ducts with
      increased polyglutamylation. These data suggest that CCP1 and CCP5 play important
      roles in developmental processes, particularly the development and functioning of
      cilia. The robust and similar defects upon knockdown suggest that each CCP may
      have a function in microtubule modification and ciliary function and that other
      CCPs are not able to compensate for the loss of one. 

PMID- 24022482
TI  - Cytosolic carboxypeptidase 5 removes alpha- and gamma-linked glutamates from
      tubulin.
AB  - Cytosolic carboxypeptidase 5 (CCP5) is a member of a subfamily of enzymes that
      cleave C-terminal and/or side chain amino acids from tubulin. CCP5 was proposed
      to selectively cleave the branch point of glutamylated tubulin, based on studies
      involving overexpression of CCP5 in cell lines and detection of tubulin forms
      with antisera. In the present study, we examined the activity of purified CCP5
      toward synthetic peptides as well as soluble alpha- and beta-tubulin and
      paclitaxel-stabilized microtubules using a combination of antisera and mass
      spectrometry to detect the products. Mouse CCP5 removes multiple glutamate
      residues and the branch point glutamate from the side chains of porcine brain
      alpha- and beta-tubulin. In addition, CCP5 excised C-terminal glutamates from
      detyrosinated alpha-tubulin. The enzyme also removed multiple glutamate residues
      from side chains and C termini of paclitaxel-stabilized microtubules. CCP5 both
      shortens and removes side chain glutamates from synthetic peptides corresponding
      to the C-terminal region of beta3-tubulin, whereas cytosolic carboxypeptidase 1
      shortens the side chain without cleaving the peptides' gamma-linked residues. The
      rate of cleavage of alpha linkages by CCP5 is considerably slower than that of
      removal of a single gamma-linked glutamate residue. Collectively, our data show
      that CCP5 functions as a dual-functional deglutamylase cleaving both alpha- and
      gamma-linked glutamate from tubulin. 

PMID- 24022484
TI  - Acidosis drives damage-associated molecular pattern (DAMP)-induced interleukin-1
      secretion via a caspase-1-independent pathway.
AB  - The proinflammatory cytokine IL-1beta is a key mediator of inflammatory responses
      that contribute to and exacerbate brain injury. IL-1beta is synthesized by
      microglia in the brain as an inactive precursor (pro-IL-1beta). Cleavage of pro
      IL-1beta to a mature form is stimulated by damage-associated molecular patterns
      (DAMPs). These DAMPs are sensed by a pattern recognition receptor called NLRP3,
      which forms an inflammasome, resulting in the activation of caspase-1 and
      cleavage of pro-IL-1beta. To date, regulation of the inflammasome in culture has
      been studied under normal culture conditions, and it is not known how DAMPs
      signal under disease relevant conditions such as acidosis. Given the presence of
      acidosis in pathological states, our objective was to test the hypothesis that
      acidic conditions modify DAMP-induced IL-1beta release from cultured primary
      mouse glial cells. When LPS-primed glial cells were stimulated with DAMPs under
      acidic conditions (pH 6.2), the predominant IL-1beta form secreted was the 20-kDa
      rather than the 17-kDa caspase-1-dependent species. Lactic acidosis, induced by
      the addition of 25 mm lactic acid, also induced the release of 20-kDa IL-1beta.
      This 20-kDa product was produced independently of NLRP3 and caspase-1 but was
      inhibited by the cathepsin D inhibitor pepstatin A. These data suggest that under
      disease relevant acidosis, DAMPs and lactic acid induce the secretion of IL-1beta
      independently of the inflammasome. Therapeutic strategies directed to the
      inhibition of IL-1beta processing should therefore consider alternative
      processing of IL-1beta in addition to caspase-1-dependent processing. 

PMID- 24022485
TI  - Peroxiredoxin chaperone activity is critical for protein homeostasis in zinc
      deficient yeast.
AB  - Zinc is required for the folding and function of many proteins. In Saccharomyces
      cerevisiae, homeostatic and adaptive responses to zinc deficiency are regulated
      by the Zap1 transcription factor. One Zap1 target gene encodes the Tsa1
      peroxiredoxin, a protein with both peroxidase and protein chaperone activities.
      Consistent with its regulation, Tsa1 is critical for growth under low zinc
      conditions. We previously showed that Tsa1's peroxidase function decreases the
      oxidative stress that occurs in zinc deficiency. In this report, we show that
      Tsa1 chaperone, and not peroxidase, activity is the more critical function in
      zinc-deficient cells. Mutations restoring growth to zinc-deficient tsa1 cells
      inactivated TRR1, encoding thioredoxin reductase. Because Trr1 is required for
      oxidative stress tolerance, this result implicated the Tsa1 chaperone function in
      tolerance to zinc deficiency. Consistent with this hypothesis, the tsa1Delta zinc
      requirement was complemented by a Tsa1 mutant allele that retained only chaperone
      function. Additionally, growth of tsa1Delta was also restored by overexpression
      of holdase chaperones Hsp26 and Hsp42, which lack peroxidase activity, and the
      Tsa1 paralog Tsa2 contributed to suppression by trr1Delta, even though trr1Delta
      inactivates Tsa2 peroxidase activity. The essentiality of the Tsa1 chaperone
      suggested that zinc-deficient cells experience a crisis of disrupted protein
      folding. Consistent with this model, assays of protein homeostasis suggested that
      zinc-limited tsa1Delta mutants accumulated unfolded proteins and induced a
      corresponding stress response. These observations demonstrate a clear
      physiological role for a peroxiredoxin chaperone and reveal a novel and
      unexpected role for protein homeostasis in tolerating metal deficiency. 

PMID- 24022486
TI  - New structural insights into phosphorylation-free mechanism for full cyclin
      dependent kinase (CDK)-cyclin activity and substrate recognition.
AB  - Pho85 is a versatile cyclin-dependent kinase (CDK) found in budding yeast that
      regulates a myriad of eukaryotic cellular functions in concert with 10 cyclins
      (called Pcls). Unlike cell cycle CDKs that require phosphorylation of a
      serine/threonine residue by a CDK-activating kinase (CAK) for full activation,
      Pho85 requires no phosphorylation despite the presence of an equivalent residue.
      The Pho85-Pcl10 complex is a key regulator of glycogen metabolism by
      phosphorylating the substrate Gsy2, the predominant, nutritionally regulated form
      of glycogen synthase. Here we report the crystal structures of Pho85-Pcl10 and
      its complex with the ATP analog, ATPgammaS. The structure solidified the
      mechanism for bypassing CDK phosphorylation to achieve full catalytic activity.
      An aspartate residue, invariant in all Pcls, acts as a surrogate for the
      phosphoryl adduct of the phosphorylated, fully activated CDK2, the prototypic
      cell cycle CDK, complexed with cyclin A. Unlike the canonical recognition motif,
      SPX(K/R), of phosphorylation sites of substrates of several cell cycle CDKs, the
      motif in the Gys2 substrate of Pho85-Pcl10 is SPXX. CDK5, an important signal
      transducer in neural development and the closest known functional homolog of
      Pho85, does not require phosphorylation either, and we found that in its crystal
      structure complexed with p25 cyclin a water/hydroxide molecule remarkably plays a
      similar role to the phosphoryl or aspartate group. Comparison between Pho85
      Pcl10, phosphorylated CDK2-cyclin A, and CDK5-p25 complexes reveals the
      convergent structural characteristics necessary for full kinase activity and the
      variations in the substrate recognition mechanism. 

PMID- 24022487
TI  - Repetitive protein unfolding by the trans ring of the GroEL-GroES chaperonin
      complex stimulates folding.
AB  - A key constraint on the growth of most organisms is the slow and inefficient
      folding of many essential proteins. To deal with this problem, several diverse
      families of protein folding machines, known collectively as molecular chaperones,
      developed early in evolutionary history. The functional role and operational
      steps of these remarkably complex nanomachines remain subjects of active debate.
      Here we present evidence that, for the GroEL-GroES chaperonin system, the non
      native substrate protein enters the folding cycle on the trans ring of the double
      ring GroEL-ATP-GroES complex rather than the ADP-bound complex. The properties of
      this ATP complex are designed to ensure that non-native substrate protein binds
      first, followed by ATP and finally GroES. This binding order ensures efficient
      occupancy of the open GroEL ring and allows for disruption of misfolded
      structures through two phases of multiaxis unfolding. In this model, repeated
      cycles of partial unfolding, followed by confinement within the GroEL-GroES
      chamber, provide the most effective overall mechanism for facilitating the
      folding of the most stringently dependent GroEL substrate proteins. 

PMID- 24022488
TI  - How a CCA sequence protects mature tRNAs and tRNA precursors from action of the
      processing enzyme RNase BN/RNase Z.
AB  - In many organisms, 3' maturation of tRNAs is catalyzed by the endoribonuclease,
      RNase BN/RNase Z, which cleaves after the discriminator nucleotide to generate a
      substrate for addition of the universal CCA sequence. However, tRNAs or tRNA
      precursors that already contain a CCA sequence are not cleaved, thereby avoiding
      a futile cycle of removal and readdition of these essential residues. We show
      here that the adjacent C residues of the CCA sequence and an Arg residue within a
      highly conserved sequence motif in the channel leading to the RNase catalytic
      site are both required for the protective effect of the CCA sequence. When both
      of these determinants are present, CCA-containing RNAs in the channel are unable
      to move into the catalytic site; however, substitution of either of the C
      residues by A or U or mutation of Arg(274) to Ala allows RNA movement and
      catalysis to proceed. These data define a novel mechanism for how tRNAs are
      protected against the promiscuous action of a processing enzyme. 

PMID- 24022489
TI  - Structural basis of mycobacterial inhibition by cyclomarin A.
AB  - Cyclomarin A (CymA) was identified as a mycobactericidal compound targeting
      ClpC1. However, the target was identified based on pulldown experiments and in
      vitro binding data, without direct functional evidence in mycobacteria. Here we
      show that CymA specifically binds to the N-terminal domain of ClpC1. In addition
      we have determined the co-crystal structure of CymA bound to the N-terminal
      domain of ClpC1 to high resolution. Based on the structure of the complex several
      mutations were engineered into ClpC1, which showed reduced CymA binding in vitro.
      The ClpC1 mutants were overexpressed in mycobacteria and two showed resistance to
      CymA, providing the first direct evidence that ClpC1 is the target of CymA.
      Phe(80) is important in vitro and in cells for the ClpC1-CymA interaction and
      this explains why other bacteria are resistant to CymA. A model for how CymA
      binding to the N-terminal domain of ClpC1 leads to uncontrolled proteolysis by
      the associated ClpP protease machinery is discussed. 

PMID- 24022490
TI  - CR1-mediated ATP release by human red blood cells promotes CR1 clustering and
      modulates the immune transfer process.
AB  - Humans and other higher primates are unique among mammals in using complement
      receptor 1 (CR1, CD35) on red blood cells (RBC) to ligate complement-tagged
      inflammatory particles (immune complexes, apoptotic/necrotic debris, and
      microbes) in the circulation for quiet transport to the sinusoids of spleen and
      liver where resident macrophages remove the particles, but allow the RBC to
      return unharmed to the circulation. This process is called immune-adherence
      clearance. In this study we found using luminometric- and fluorescence-based
      methods that ligation of CR1 on human RBC promotes ATP release. Our data show
      that CR1-mediated ATP release does not depend on Ca(2+) or enzymes previously
      shown to mediate an increase in membrane deformability promoted by CR1 ligation.
      Furthermore, ATP release following CR1 ligation increases the mobility of the
      lipid fraction of RBC membranes, which in turn facilitates CR1 clustering, and
      thereby enhances the binding avidity of complement-opsonized particles to the RBC
      CR1. Finally, we have found that RBC-derived ATP has a stimulatory effect on
      phagocytosis of immune-adherent immune complexes. 

PMID- 24022491
TI  - Inhibition of amyloid precursor protein processing enhances gemcitabine-mediated
      cytotoxicity in pancreatic cancer cells.
AB  - Pancreatic adenocarcinoma or pancreatic cancer is often diagnosed at a very late
      stage at which point treatment options are minimal. Current chemotherapeutic
      interventions prolong survival marginally, thereby emphasizing the acute need for
      better treatment options to effectively manage this disease. Studies from
      different laboratories have shown that the Alzheimer disease-associated amyloid
      precursor protein (APP) is overexpressed in various cancers but its significance
      is not known. Here we sought to determine the role of APP in pancreatic cancer
      cell survival and proliferation. Our results show that pancreatic cancer cells
      secrete high levels of sAPPalpha, the alpha-secretase cleaved ectodomain fragment
      of APP, as compared with normal non-cancerous cells. Treatment of cells with
      batimastat or GI254023X, inhibitors of the alpha-secretase ADAM10, prevented
      sAPPalpha generation and reduced cell survival. Additionally, inhibition of
      sAPPalpha significantly reduced anchorage independent growth of the cancer cells.
      The effect of batimastat on cell survival and colony formation was enhanced when
      sAPPalpha downregulation was combined with gemcitabine treatment. Moreover,
      treatment of batimastat-treated cells with recombinant sAPPalpha reversed the
      inhibitory effect of the drug thereby indicating that sAPPalpha can indeed induce
      proliferation of cancer cells. Down-regulation of APP and ADAM10 brought about
      similar results, as did batimastat treatment, thereby confirming that APP
      processing is important for growth and proliferation of these cells. These
      results suggest that inhibition of sAPPalpha generation might enhance the
      effectiveness of the existing chemotherapeutic regimen for a better outcome. 

PMID- 24022492
TI  - Spermidine stimulates T cell protein-tyrosine phosphatase-mediated protection of
      intestinal epithelial barrier function.
AB  - The gene locus encoding protein-tyrosine phosphatase non-receptor type 2 (PTPN2)
      has been associated with inflammatory bowel disease. Expression of the PTPN2 gene
      product, T cell protein-tyrosine phosphatase (TCPTP), in intestinal epithelial
      cells has been shown to play an important role in the protection of epithelial
      barrier function during periods of inflammation by acting as a negative regulator
      of the proinflammatory cytokine IFN-gamma. Therefore, agents that increase the
      activity of TCPTP are of general interest as modifiers of inflammatory signaling
      events. A previous study demonstrated that the small molecule spermidine is a
      selective activator of TCPTP in vitro. The aim of this study was to investigate
      whether activation of TCPTP by spermidine was capable of alleviating IFN-gamma
      induced, proinflammatory signaling and barrier dysfunction in human intestinal
      epithelial cells. Studies revealed that treatment of T84 and HT29/cl.19A
      colonocytes with spermidine increased both TCPTP protein levels and enzymatic
      activity, correlating with a decrease in the phosphorylation of the signal
      transducers and activators of transcription 1 and 3, downstream mediators of IFN
      gamma signaling, upon coadministration of spermidine to IFN-gamma-treated cells.
      On a functional level, spermidine protected barrier function in the setting of
      inflammation, restricting the decrease in transepithelial electrical resistance
      and the increase in epithelial permeability induced by IFN-gamma in coincubation
      experiments. These data implicate spermidine as a potential therapeutic agent to
      treat conditions associated with elevated IFN-gamma signaling and a faulty
      mucosal barrier. 

PMID- 24022493
TI  - Production of hesperetin using a covalently multipoint immobilized diglycosidase
      from Acremonium sp. DSM24697.
AB  - The diglycosidase alpha-rhamnosyl-beta-glucosidase (EC 3.2.1.168) from the fungus
      Acremonium sp. DSM24697 was immobilized on several agarose-based supports.
      Covalent multipoint immobilization onto glyoxyl-activated agarose was selected as
      the more stable preparation at high concentration of dimethyl sulfoxide (DMSO)
      and high temperature. The optimal conditions for the immobilization process
      involved an incubation of the enzyme with agarose beads containing 220 MUmol of
      glyoxyl groups per gram at pH 10 and 25 degrees C for 24 h. The hydrolysis of
      hesperidin carried out in 10% v/v DMSO at 60 degrees C for 2 h reached 64.6%
      substrate conversion and a specific productivity of 2.40 mmol h(-1) g(-1). Under
      these conditions, the process was performed reutilizing the catalyst for up to 18
      cycles, maintaining >80% of the initial activity and a constant productivity 2.96
      +/- 0.42 umol(-1) h(-1) g(-1). To the best of our knowledge, such productivity is
      the highest achieved for hesperetin production through an enzymatic approach.

PMID- 24022494
TI  - Reply: To PMID 22653544.

PMID- 24022495
TI  - Extending glacial refugia for a European tree: genetic markers show that Iberian
      populations of white elm are native relicts and not introductions.
AB  - Conservation policies usually focus on in situ protection of native populations,
      a priority that requires accurate assessment of population status. Distinction
      between native and introduced status can be particularly difficult (and at the
      same time, is most important) for species whose natural habitat has become both
      rare and highly fragmented. Here, we address the status of the white elm (Ulmus
      laevis Pallas), a European riparian tree species whose populations have been
      fragmented by human activity and is protected wherever it is considered native.
      Small populations of this species are located in Iberia, where they are
      unprotected because they are considered introductions due to their rarity.
      However, Iberia and neighbouring regions in southwestern France have been shown
      to support discrete glacial refuge populations of many European trees, and the
      possibility remains that Iberian white elms are native relicts. We used
      chloroplast RFLPs and nuclear microsatellites to establish the relationship
      between populations in Iberia and the Central European core distribution.
      Bayesian approaches revealed significant spatial structure across populations.
      Those in Iberia and southwestern France shared alleles absent from Central
      Europe, and showed spatial population structure within Iberia common in
      recognized native taxa. Iberian populations show a demographic signature of
      ancient population bottlenecks, while those in Central European show a signature
      of recent population bottlenecks. These patterns are not consistent with
      historical introduction of white elm to Iberia, and instead strongly support
      native status, arguing for immediate implementation of conservation measures for
      white elm populations in Spain and contiguous areas of southern France.

PMID- 24022496
TI  - 'Escaping' the X chromosome leads to increased gene expression in the male
      germline of Drosophila melanogaster.
AB  - Genomic analyses of Drosophila species suggest that the X chromosome presents an
      unfavourable environment for the expression of genes in the male germline. A
      previous study in D. melanogaster used a reporter gene driven by a testis
      specific promoter to show that expression was greatly reduced when the gene was
      inserted onto the X chromosome as compared with the autosomes. However, a
      limitation of this study was that only the expression regulated by a single,
      autosomal-derived promoter was investigated. To test for an increase in
      expression associated with 'escaping' the X chromosome, we analysed reporter gene
      expression driven by the promoters of three X-linked, testis-expressed genes
      (CG10920, CG12681 and CG1314) that were inserted randomly throughout the D.
      melanogaster genome. In all cases, insertions on the autosomes showed
      significantly higher expression than those on the X chromosome. Thus, even genes
      whose regulation has adapted to the X-chromosomal environment show increased male
      germline expression when relocated to an autosome. Our results provide direct
      experimental evidence for the suppression of X-linked gene expression in the
      Drosophila male germline that is independent of gene dose.

PMID- 24022497
TI  - A genome-wide scan study identifies a single nucleotide substitution in ASIP
      associated with white versus non-white coat-colour variation in sheep (Ovis
      aries).
AB  - In sheep, coat colour (and pattern) is one of the important traits of great
      biological, economic and social importance. However, the genetics of sheep coat
      colour has not yet been fully clarified. We conducted a genome-wide association
      study of sheep coat colours by genotyping 47 303 single-nucleotide polymorphisms
      (SNPs) in the Finnsheep population in Finland. We identified 35 SNPs associated
      with all the coat colours studied, which cover genomic regions encompassing three
      known pigmentation genes (TYRP1, ASIP and MITF) in sheep. Eighteen of these
      associations were confirmed in further tests between white versus non-white
      individuals, but none of the 35 associations were significant in the analysis of
      only non-white colours. Across the tests, the s66432.1 in ASIP showed significant
      association (P=4.2 * 10(-11) for all the colours; P=2.3 * 10(-11) for white
      versus non-white colours) with the variation in coat colours and strong linkage
      disequilibrium with other significant variants surrounding the ASIP gene. The
      signals detected around the ASIP gene were explained by differences in white
      versus non-white alleles. Further, a genome scan for selection for white coat
      pigmentation identified a strong and striking selection signal spanning ASIP. Our
      study identified the main candidate gene for the coat colour variation between
      white and non-white as ASIP, an autosomal gene that has been directly implicated
      in the pathway regulating melanogenesis. Together with ASIP, the two other newly
      identified genes (TYRP1 and MITF) in the Finnsheep, bordering associated SNPs,
      represent a new resource for enriching sheep coat-colour genetics and breeding.

PMID- 24022498
TI  - Scaling of processes shaping the clonal dynamics and genetic mosaic of seagrasses
      through temporal genetic monitoring.
AB  - Theoretically, the dynamics of clonal and genetic diversities of clonal plant
      populations are strongly influenced by the competition among clones and rate of
      seedling recruitment, but little empirical assessment has been made of such
      dynamics through temporal genetic surveys. We aimed to quantify 3 years of
      evolution in the clonal and genetic composition of Zostera marina meadows,
      comparing parameters describing clonal architecture and genetic diversity at nine
      microsatellite markers. Variations in clonal structure revealed a decrease in the
      evenness of ramet distribution among genets. This illustrates the increasing
      dominance of some clonal lineages (multilocus lineages, MLLs) in populations.
      Despite the persistence of these MLLs over time, genetic differentiation was much
      stronger in time than in space, at the local scale. Contrastingly with the short
      term evolution of clonal architecture, the patterns of genetic structure and
      genetic diversity sensu stricto (that is, heterozygosity and allelic richness)
      were stable in time. These results suggest the coexistence of (i) a fine grained
      (at the scale of a 20 * 30 m quadrat) stable core of persistent genets
      originating from an initial seedling recruitment and developing spatial dominance
      through clonal elongation; and (ii) a local (at the scale of the meadow) pool of
      transient genets subjected to annual turnover. This simultaneous occurrence of
      initial and repeated recruitment strategies highlights the different spatial
      scales at which distinct evolutionary drivers and mating systems (clonal
      competition, clonal growth, propagule dispersal and so on) operate to shape the
      dynamics of populations and the evolution of polymorphism in space and time.

PMID- 24022499
TI  - A two-dimensional model for the study of interpersonal attraction.
AB  - We describe a model for understanding interpersonal attraction in which
      attraction can be understood as a product of the initial evaluations we make
      about others. The model posits that targets are evaluated on two basic
      dimensions, capacity and willingness, such that affective and behavioral
      attraction result from evaluations of (a) a target's capacity to facilitate the
      perceiver's goals/needs and (b) a target's potential willingness to facilitate
      those goals/needs. The plausibility of the two-dimensional model of attraction is
      evaluated vis-a-vis the extant literature on various attraction phenomena
      including the reciprocity of liking effect, pratfall effect, matching hypothesis,
      arousal effects, and similarity effect. We conclude that considerable evidence
      across a wide range of phenomena supports the idea that interpersonal attraction
      is principally determined by inferences about the target's capacity and
      willingness. 

PMID- 24022500
TI  - Dual-energy x-ray absorptiometry: interpreting reports and serial measurements.
AB  - Physicians and other health care providers requesting dual-energy x-ray bone
      density studies must be able to critically review and interpret such studies.
      This requires an understanding of the computerized result components of the
      studies and how such data can be applied in clinical practice. The timing and
      interpretation of serial bone density studies is governed by the concepts of
      precision and least significant change. These statistical concepts are well
      within the purview of the practicing physician. Serial bone density studies
      cannot be interpreted without prior knowledge of the precision and least
      significant change of the test. 

PMID- 24022501
TI  - Controversies in osteoporosis management: how do you treat a newly menopausal
      woman with low bone mass: when and how is it appropriate to provide pharmacologic
      intervention to prevent osteoporosis?

PMID- 24022502
TI  - Bone density measurement and assessment of fracture risk.
AB  - The most useful methods for estimating fracture risk are bone mineral density
      (BMD) testing by dual-energy x-ray absorptiometry and consideration of clinical
      risk factors (CRFs) for fracture. The combination of BMD and CRFs predicts
      fractures better than BMD or CRFs alone. FRAX is a computer-based fracture risk
      algorithm developed by the World Health Organization to estimate fracture
      probability using validated CRFs and femoral neck BMD, when available. BMD and
      FRAX are included in clinical practice guidelines to identify patients at high
      fracture risk who are most likely to benefit from pharmacologic therapy to reduce
      fracture risk. 

PMID- 24022504
TI  - Insulin analogues in the treatment of gestational diabetes mellitus.
AB  - Rapid-acting insulin analogues are the preferred choice for short-acting insulin
      due to their superior pharmacologic profiles, leading to greater flexibility and
      convenience of dosing. This has lead to greater patient satisfaction and improved
      quality of life. Clinical experience with rapid-acting insulin analogues in
      pregnancy is increasing. Currently, there is limited data available on the use of
      long-acting insulin analogues in pregnancy. The focus of this review is to
      discuss the role of insulin analogue therapy in the treatment of the woman with
      gestational diabetes. 

PMID- 24022503
TI  - Premenopausal bone health: osteoporosis in premenopausal women.
AB  - This article will discuss the diagnosis of osteoporosis in premenopausal women
      and the evaluation and management of those with low-trauma fractures and/or low
      bone mineral density. As secondary causes (glucocorticoid excess, anorexia
      nervosa, premenopausal estrogen deficiency, and celiac disease) are commonly the
      underlying cause of osteoporosis in this population, treatment of the underlying
      condition should be the focus of management. Additional management options,
      generally reserved for those with major or multiple fractures and/or ongoing bone
      loss, will also be described. 

PMID- 24022505
TI  - Cognitive psychosocial intervention in dementia: a systematic review.
AB  - BACKGROUND: The evolution of dementia depends on the underlying pathology, early
      diagnosis and the availability of effective treatment for some of the symptoms
      that interfere with the patients' or caregivers' quality of life. Even though
      there is no specific treatment to reverse dementia, some interventions such as
      reality orientation and skills training can retard cognitive impairment. AIM: To
      review existing scientific evidence regarding the efficacy of therapies included
      in the category of cognition-oriented approaches for people suffering from
      dementia. METHODS: Papers were retrieved from several bibliographic databases
      (last publication date: 2009) with pre-specified selection criteria, data
      extraction and methodological quality assessment. RESULTS: Nine reality
      orientation and 8 skills training trials were identified as meeting the inclusion
      criteria. CONCLUSIONS: Stimulation of cognitive functions, especially by means of
      reality orientation, improves overall cognitive function in patients suffering
      from dementia.

PMID- 24022507
TI  - Bubble bouncing at a clean water surface.
AB  - Experiments on the coalescence time of submillimeter bubbles colliding with a
      distilled water/air interface either being at rest (undisturbed) or vibrating
      vertically (with controlled amplitude and frequency) were carried out. It was
      found that the outcome of the bubble collision (coalescence or bounce) depends on
      impact velocity and size of the bubble, i.e. the parameters determining the
      bubble deformation degree. With the surface at rest, when the deformation of the
      bubble was sufficiently high, bubble bouncing was observed. It was caused by the
      fact that the radius of the intervening liquid film formed between the colliding
      bubble and water/air interface was large enough to prevent the liquid layer from
      reaching its thickness of rupture within the time of bubble-interface contact.
      Coalescence occurred in a consecutive collision if the bubble deformation was
      below a threshold value, as a result of dissipation of the kinetic energy
      associated with the bubble motion. The hypothesis about the crucial role of the
      bubble deformation and size of the liquid film formed in the bouncing mechanism
      was confirmed in a series of experiments where the bubble collided with a
      vibrating water/air interface. It was shown that when the kinetic energy was
      properly re-supplied from an external source (interface vibrations), the
      spectacular phenomenon of "immortal" bubbles, dancing indefinitely at the
      water/air interface, was achieved. It was shown that "immortal" bubble formation
      is a consequence of a similarly high degree of the bubble shape deformation and
      consequently a large enough radius of the liquid film formed. 

PMID- 24022506
TI  - Amyloid-beta nanotubes are associated with prion protein-dependent
      synaptotoxicity.
AB  - Growing evidence suggests water-soluble, non-fibrillar forms of amyloid-beta
      protein (Abeta) have important roles in Alzheimer's disease with toxicities
      mimicked by synthetic Abeta(1-42). However, no defined toxic structures acting
      via specific receptors have been identified and roles of proposed receptors, such
      as prion protein (PrP), remain controversial. Here we quantify binding to PrP of
      Abeta(1-42) after different durations of aggregation. We show PrP-binding and PrP
      dependent inhibition of long-term potentiation (LTP) correlate with the presence
      of protofibrils. Globular oligomers bind less avidly to PrP and do not inhibit
      LTP, whereas fibrils inhibit LTP in a PrP-independent manner. That only certain
      transient Abeta assemblies cause PrP-dependent toxicity explains conflicting
      reports regarding the involvement of PrP in Abeta-induced impairments. We show
      that these protofibrils contain a defined nanotubular structure with a previously
      unidentified triple helical conformation. Blocking the formation of Abeta
      nanotubes or their interaction with PrP might have a role in treatment of
      Alzheimer's disease.

PMID- 24022508
TI  - Expression of GABAA alpha2-, beta1- and epsilon-receptors are altered
      significantly in the lateral cerebellum of subjects with schizophrenia, major
      depression and bipolar disorder.
AB  - There is abundant evidence that dysfunction of the gamma-aminobutyric acid
      (GABA)ergic signaling system is implicated in the pathology of schizophrenia and
      mood disorders. Less is known about the alterations in protein expression of GABA
      receptor subunits in brains of subjects with schizophrenia and mood disorders. We
      have previously demonstrated reduced expression of GABA(B) receptor subunits 1
      and 2 (GABBR1 and GABBR2) in the lateral cerebella of subjects with
      schizophrenia, bipolar disorder and major depressive disorder. In the current
      study, we have expanded these studies to examine the mRNA and protein expression
      of 12 GABA(A) subunit proteins (alpha1, alpha2, alpha3, alpha5, alpha6, beta1,
      beta2, beta3, delta, epsilon, gamma2 and gamma3) in the lateral cerebella from
      the same set of subjects with schizophrenia (N=9-15), bipolar disorder (N=10-15)
      and major depression (N=12-15) versus healthy controls (N=10-15). We found
      significant group effects for protein levels of the alpha2-, beta1- and epsilon
      subunits across treatment groups. We also found a significant group effect for
      mRNA levels of the alpha1-subunit across treatment groups. New avenues for
      treatment, such as the use of neurosteroids to promote GABA modulation, could
      potentially ameliorate GABAergic dysfunction in these disorders.

PMID- 24022510
TI  - Convergent functional genomics of stem cell-derived cells.
AB  - Stem cell technologies provide an exciting avenue to directly access the
      transcriptome of patients in neuronal-like cell types, which might have more
      direct relevance to brain research than other peripheral tissues (blood,
      fibroblasts). Enthusiasm should be tempered by concerns that artifacts and noise
      might be generated as part of the in vitro process of creating and maintaining
      these cell type. A solution may be to apply a Convergent Functional Genomics
      approach, where the data from stem cell-derived neuronal cells are integrated,
      cross-validated and prioritized using independent lines of evidence from other
      approaches and platforms (human genetic data, human postmortem brain data, animal
      model data). I provide a brief overview and an example in support of such an
      approach. 

PMID- 24022509
TI  - Opposing actions of environmental enrichment and Alzheimer's disease on the
      expression of hippocampal microRNAs in mouse models.
AB  - Alzheimer's disease (AD) is the most common form of dementia in the elderly.
      Although there are no drugs that modify the disease process, exposure to an
      enriched environment (EE) can slow the disease progression. Here, we characterize
      the effects of AD and EE on the post-transcriptional regulators, microRNAs
      (miRNAs), which may contribute to the detrimental and beneficial effects of AD
      and EE, respectively, on synaptic plasticity-related proteins and AD pathology.
      We found for the first time miRNAs that were inversely regulated in AD and EE,
      and may affect synaptic proteins and modulators, molecular factors associated
      with AD pathology, and survival and neuroprotective factors. MiRNAs that were
      upregulated only in 3xTgAD mice model of AD compared with their control mice were
      localized to synapses, predicted to downregulate essential synaptic proteins and
      are highly associated with regulating apoptosis, AD-associated processes and axon
      guidance. Studying the progressive change in miRNAs modulation during aging of
      3xTgAD mice, we identified miRNAs that were regulated in earlier stages of AD,
      suggesting them as potential AD biomarkers. Last, we characterized AD- and EE
      related effects in the mouse hippocampus on tomosyn protein levels, an inhibitor
      of the synaptic transmission machinery. While EE reduced tomosyn levels, tomosyn
      levels were increased in old 3xTgAD mice, suggesting a role for tomosyn in the
      impairment of synaptic transmission in AD. Interestingly, we found that miR-325
      regulates the expression levels of tomosyn as demonstrated by a luciferase
      reporter assay, and that miR-325 was downregulated in AD and upregulated
      following EE. These findings improve our understanding of the molecular and
      cellular processes in AD pathology, following EE, and the interplay between the
      two processes, and open new avenues for the studies of understanding and
      controlling AD. 

PMID- 24022511
TI  - The STIL protein contains intrinsically disordered regions that mediate its
      protein-protein interactions.
AB  - The STIL protein participates in mitosis and malignant transformation by
      regulating centrosomal duplication. Using biophysical methods we studied the
      structure and interactions of STIL. We revealed that its central domain is
      intrinsically disordered and mediates protein-protein interactions of STIL. The
      intrinsic disorder may provide STIL with the conformational flexibility required
      for its multitude binding. 

PMID- 24022512
TI  - Comparison of two surgical techniques for complete atrioventricular septal defect
      repair using two- and three-dimensional echocardiography.
AB  - Different surgical techniques for complete atrioventricular septal defect (CAVSD)
      repair have been described, with the double-patch technique being most frequently
      employed. More recently a newer technique using a modified single-patch repair
      has been advocated. We hypothesized that the modified single-patch technique
      would result in an increased incidence of the two major post-repair
      comorbidities, namely, distortion of the left AV valve (LAVV) leaflets and
      narrowing of the left-ventricular outflow tract (LVOT). We studied 14 patients
      with CAVSD who underwent either traditional double-patch technique [group 1 (n =
      7)] or modified single-patch technique [group 2 (n = 7)]. Preoperative and
      immediate postoperative two-dimensional (2D) echocardiograms, as well as follow
      up 2D and three-dimensional (3D) studies, were reviewed. For group 1, the median
      age at repair was 4.1 months with a median duration from surgical repair and last
      echocardiogram of 44 months. For group 2, the median age at repair was 3 months
      with a median duration from surgical repair and last echocardiogram of 28 months.
      The two groups had similar demographics and ventricular septal defect size before
      surgery. For the LAVV, no significant difference was observed with respect to
      LAVV annulus size, tenting height, and the size of the vena contracta.
      Furthermore, there was no significant difference in the 2D echocardiographic
      areas and volumes of the LVOT between pre-repair and immediate post-repair
      studies for both groups. At the last evaluation, although there had been growth
      of the LVOT in both groups, no significant difference between areas and volumes
      were observed. Areas of the LVOT measured by 3D echocardiography on the final
      study showed no significant statistical difference between both groups. There was
      good correlation of the areas measured by 2D and 3D echocardiography within each
      group. In this small group, modified single-patch technique does not appear to
      tether the LAVV or promote an increase in regurgitation. In the short term, LVOT
      growth is unaffected, and the repair does not promote LVOT obstruction. 3D
      echocardiography is useful for area measurements of the LVOT and showed good
      correlation with areas measured by assumption of the LVOT shape as determined
      using 2D techniques.

PMID- 24022514
TI  - Pancreatic stent migration into the bile duct causing cholangitis.

PMID- 24022513
TI  - The role of calcium in the prevention of cardiovascular disease--a review of
      observational studies and randomized clinical trials.
AB  - Calcium is a mineral that is important for bone health and has also been
      suggested to play a role in the prevention of cardiovascular disease (CVD).
      Lately, the potential effects of both inadequate and excessive calcium intake
      have received growing attention. In this review, we summarize the evidence from
      experimental, epidemiologic, and clinical studies investigating the role of
      calcium intake, either from the diet or from supplements, as well as blood
      concentrations, in relation to the risk of CVD in adults. In vitro and in vivo
      laboratory studies suggest that calcium may be involved in CVD development
      through multiple pathways, including blood cholesterol, insulin secretion and
      sensitivity, vasodilation, inflammatory profile, thrombosis, obesity, and
      vascular calcification. Several prospective epidemiologic studies have examined
      how dietary or supplemental calcium intake is associated with CVD incidence or
      mortality in middle-aged and older adults, and the results are inconsistent.
      Prospective studies investigating blood concentrations of calcium have also
      reported mixed results. However, changes in blood calcium concentrations may
      reflect a disturbed calcium phosphate balance, which is associated with increased
      risk of CVD. To date there is no randomized clinical trial that has been designed
      specifically to test the effect of calcium supplementation on the risk of CVD as
      the primary end point. Existing trials have performed secondary analyses, and
      most of them have been conducted among postmenopausal women. These trials suggest
      that calcium supplementation has no effect on CVD development; however, they do
      not allow a definitive conclusion to be drawn. The average daily intake of
      calcium is low in many populations; however, the evidence for a potential role of
      dietary or supplemental calcium in the prevention of CVD remains insufficient and
      inconclusive. Only large-scale randomized trials designed to investigate the
      effects of calcium supplementation on CVD events as the primary end point, as
      well as short-term trials investigating the effect on coronary biomarkers, can
      provide a definitive answer. 

PMID- 24022515
TI  - Fabrication, operation and flow visualization in surface-acoustic-wave-driven
      acoustic-counterflow microfluidics.
AB  - Surface acoustic waves (SAWs) can be used to drive liquids in portable
      microfluidic chips via the acoustic counterflow phenomenon. In this video we
      present the fabrication protocol for a multilayered SAW acoustic counterflow
      device. The device is fabricated starting from a lithium niobate (LN) substrate
      onto which two interdigital transducers (IDTs) and appropriate markers are
      patterned. A polydimethylsiloxane (PDMS) channel cast on an SU8 master mold is
      finally bonded on the patterned substrate. Following the fabrication procedure,
      we show the techniques that allow the characterization and operation of the
      acoustic counterflow device in order to pump fluids through the PDMS channel
      grid. We finally present the procedure to visualize liquid flow in the channels.
      The protocol is used to show on-chip fluid pumping under different flow regimes
      such as laminar flow and more complicated dynamics characterized by vortices and
      particle accumulation domains. 

PMID- 24022516
TI  - Artery phantoms for intravascular optical coherence tomography: diseased
      arteries.
AB  - We propose and test various strategies for the creation of artery phantoms
      mimicking different kinds of diseased arteries when imaged by intravascular
      optical coherence tomography (IVOCT). We first review the method for making
      healthy artery phantoms. We then describe the procedure to fabricate diseased
      artery phantoms with intima thickening, lipid pool, thin-capped fibroatheroma,
      calcification, and restenosis (homogeneous and layered) after stent apposition.
      For each case, a phantom is fabricated, an IVOCT image is obtained, and the image
      is compared to that of a real artery.

PMID- 24022517
TI  - Selective nitrogen doping in graphene for oxygen reduction reactions.
AB  - Nitrogen-doped graphene materials with abundant pyridinic and quaternary nitrogen
      species were selectively synthesized by thermal surface polymerization of
      nitrogen-containing aromatic molecules. Catalytic studies revealed that the
      oxygen reduction by nitrogen-doped graphene, containing pyridinic and quaternary
      nitrogen species, proceeds via a four- and two-electron reduction pathway,
      respectively, in alkali-based solutions. 

PMID- 24022518
TI  - Toxic effects of triclosan on the detoxification system and breeding of Daphnia
      magna.
AB  - The toxic effects of different concentrations of Triclosan (TCS) (1-128 MUg/L) on
      Daphnia magna (D. magna) were investigated by acute (48 h) and chronic (21-day)
      toxicity tests. The response of antioxidase system and Phase I metabolism process
      of D. magna exposed to TCS were investigated by measuring a series of biomarkers
      including glutathione S-transferase (GST), catalase (CAT), superoxide dismutase
      (SOD), malondialdehyde (MDA), 7-ethoxyresorufin O-deethylase (EROD), Erythromycin
      N-demethylase (ERND) and Aminopyrine N-demethylase (APND). The 48 h LC50 of TCS
      was 330 MUg/L for D. magna. In the chronic test, total number of neonates per
      female, body length and the intrinsic rate of natural increase (r) of D. magna
      increased at the low exposure concentrations (1-16 MUg/L) and decreased at the
      high concentrations (64-128 MUg/L), while the total number of molting per adult
      decreased continually. The GST and CAT activities showed no significant increase
      in all treatments, and SOD activities were induced after 24-h exposure and
      inhibited after 48-h exposure at 4-128 MUg/L of concentrations. The MDA content
      increased after 6-h exposure but decreased after 48-h exposure at 4-128 MUg/L.
      EROD activities initially increased after 6-h exposure, but decreased after 24
      and 48-h exposure, ERND and APND activities showed a similar temporal pattern
      among different treatments groups. SOD, MDA and APND were sensitive to TCS, thus
      they are suitable as potential biomarkers for the exposure to TCS.

PMID- 24022520
TI  - Knowledge and prevention practices before breast cancer diagnosis in a cross
      sectional study among survivors: impact on patients' involvement in the decision
      making process.
AB  - Disparities exist in breast cancer knowledge and education, which tend to
      influence symptom interpretation and decision to seek screening/care. The present
      project describes a cohort of women's experiences, knowledge, and health behavior
      prior to and after a diagnosis of breast cancer. It also studies how knowledge
      and demographic factors are associated with level of involvement participants had
      in the treatment of their breast cancer. Women >18 years who have been diagnosed
      and treated for breast cancer within 10 years were recruited in Pittsburgh, PA,
      through the Healthy People Cohort Registry, a database of volunteers from the
      community, and Brooklyn, NY, through the American Cancer Society breast cancer
      survivor database. Subsequent to institutional ethics approval, a questionnaire
      was administered by mail and through an electronic interactive format. The study
      included 124 breast cancer survivors, one-quarter of whom were of African
      ancestry. Roughly half of the women indicated that their overall knowledge of
      breast cancer was limited before diagnosis; no significant association between
      overall knowledge before diagnosis and stage at diagnosis or an active role of
      the patient in treatment choices was observed. Two-third of the women reported
      using personal research on internet, books, and other media to increase knowledge
      on breast cancer after diagnosis; the improvement of knowledge was associated
      with an active role in therapy choice. White women's self report of breast cancer
      knowledge prior to diagnosis was higher than that of women of African origin (p =
      0.03); the latter experienced more delays in getting results about the diagnosis
      (p = 0.002), in starting treatment (p = 0.03), and in having treatment available
      at local facilities (p = 0.007) than white women. White women were more likely to
      improve their knowledge through their own research (p = 0.08) and through the
      contribution of their physician (p = 0.06) than women of African origin.There is
      still a need for addressing breast cancer knowledge among black women, and
      improvement in physician emotional support and in their contribution to the
      patient's knowledge is necessary. These efforts may have a positive impact on
      breast cancer knowledge among black women in the US.

PMID- 24022521
TI  - Population genetic analysis and origin discrimination of snow crab (Chionoecetes
      opilio) using microsatellite markers.
AB  - Major habitats for the snow crab Chionoecetes opilio are mostly found within the
      northwest Atlantic and North Pacific Oceans. However, the East Sea populations of
      C. opilio, along with its relative the red snow crab (C. japonicas), are two of
      the most important commercial crustacean species for fisheries on the east coast
      of the Korean Peninsula. The East Sea populations of C. opilio are facing
      declining resources due to overfishing and global climate change. Thus, an
      analysis of population structure is necessary for future management. Five Korean
      and one Russian group of C. opilio were analyzed using nine microsatellite
      markers that were recently developed using next-generation sequencing. No linkage
      disequilibrium was found between any pair of loci, indicating that the markers
      were independent. The number of alleles per locus varied from 4 to 18 with a mean
      of 12, and allelic richness per locus ranged from 4.0 to 17.1 across all
      populations with a mean of 9.7. The Hardy-Weinberg equilibrium test revealed
      significant deviation in three out of nine loci in some populations after
      sequential Bonferroni correction and all of them had higher expected
      heterozygosity than observed heterozygosity. Null alleles were presumed in four
      loci, which explained the homozygosity in three loci. The pairwise fixation index
      (F ST ) values among the five Korean snow crab populations did not differ
      significantly, but all of the pairwise F ST values between each of the Korean
      snow crab populations and the Russian snow crab population differed
      significantly. An UPGMA dendrogram revealed clear separation of the Russian snow
      crab population from the Korean snow crab populations. Assignment tests based on
      the allele distribution discriminated between Korean and Russian origins with 93
      % accuracy. Therefore, the snow crab populations around the Korean Peninsula need
      to be managed separately from the populations in Bering Sea in global scale
      resource management. Also, this information can be used for identification of
      snow crab origin which is problematic in worldwide crab trade.

PMID- 24022522
TI  - Arboreal adaptations of body fat in wild toque macaques (Macaca sinica) and the
      evolution of adiposity in primates.
AB  - There is a paucity of information on body composition and fat patterning in wild
      nonhuman primates. Dissected adipose tissue from wild toque macaques (Macaca
      sinica) (WTM), feeding on a natural diet, accounted for 2.1% of body weight. This
      was far less than fatness reported for nonhuman primates raised in captivity or
      for contemporary humans. In WTM, fatness increased with age and diet richness,
      but did not differ by sex. In WTM (none of which were obese) intra-abdominal fat
      filled first, and "excess" fat was stored peripherally in a ratio of about 6:1.
      Intermuscular fat was minimal (0.1%). The superficial paunch held <15% of
      subcutaneous fat weight in contrast to its much larger proportions in obese
      humans and captive monkeys where most added fat accumulates subcutaneously. With
      increasing total adiposity, accumulating fat shifted in its distribution among
      eight different main internal and peripheral deposit areas-consistent with
      maintaining body balance and a low center of gravity. The available data suggest
      that, in arboreal primates, adaptations for agile locomotion and terminal branch
      feeding set constraints on the quantity and distribution of fat. The absence of a
      higher percentage of body fat in females and neonates (as are typical of humans)
      suggests that arboreal adaptations preclude the development of fat-dependent,
      large-brained infants and the adipose-rich mothers needed to sustain them. The
      lifestyle and body composition of wild primates represent a more appropriate
      model for early human foragers than well-fed captive monkeys do.

PMID- 24022523
TI  - Elevated hyaluronan and extracellular matrix metalloproteinase inducer levels in
      women with preeclampsia.
AB  - PURPOSE: Preeclampsia (PE) is a specific syndrome of pregnancy clinically
      identified by hypertension and proteinuria from the 20th week of gestation
      associated with a systemic inflammatory response and oxidative stress. While pro
      inflammatory cytokines have been extensively studied in PE, other factors in the
      circulation that also influence the magnitude of inflammation have received much
      less attention. The present study compared serum concentrations of five immune
      regulatory compounds in normotensive pregnant women and in women with gestational
      hypertension (GH) or PE. METHODS: Sixty women with PE, 53 with GH and 40
      normotensive women paired by gestational age were evaluated. Sera were evaluated
      for concentrations of extracellular matrix metalloproteinase inducer (EMMPRIN),
      hyaluronan, gelsolin, visfatin and histone 2B by ELISA. Differences between
      groups were analyzed by nonparametric tests, with a significance level of 5%.
      RESULTS: Increased levels of EMMPRIN and hyaluronan were present in preeclamptic
      women as compared to the GH and normotensive groups. There was no difference
      between groups in gelsolin, visfatin or histone 2B. CONCLUSION: Increased release
      of EMMPRIN and hyaluronan may contribute to an elevated pro-inflammatory response
      and tissue damage in women with PE.

PMID- 24022525
TI  - A quasi-liquid polymer-based cobalt redox mediator electrolyte for dye-sensitized
      solar cells.
AB  - Recently, cobalt redox electrolyte mediators have emerged as a promising
      alternative to the commonly used iodide/triiodide redox shuttle in dye-sensitized
      solar cells (DSCs). Here, we report the successful use of a new quasi-liquid,
      polymer-based electrolyte containing the Co(3+)/Co(2+) redox mediator in 3
      methoxy propionitrile solvent in order to overcome the limitations of high cell
      resistance, low diffusion coefficient and rapid recombination losses. The
      performance of the solar cells containing the polymer based electrolytes
      increased by a factor of 1.2 with respect to an analogous electrolyte without the
      polymer. The performances of the fabricated DSCs have been investigated in detail
      by photovoltaic, transient electron measurements, EIS, Raman and UV-vis
      spectroscopy. This approach offers an effective way to make high-performance and
      long-lasting DSCs. 

PMID- 24022524
TI  - Outcome after introduction of complete mesocolic excision for colon cancer is
      similar for open and laparoscopic surgical treatments.
AB  - BACKGROUND: Complete mesocolic excision (CME) and a high (apical) vascular tie
      may improve oncologic outcome after surgery for colon cancer. Our primary aim was
      to emulate a previous national result of 73.8% overall survival (OS) with both
      the open and laparoscopic techniques. METHODS: A prospective study of radical
      colon cancer was initiated in a Norwegian community teaching hospital in 2007 and
      comprised a consecutive group of 251 patients with TNM stages I-III that had
      surgery according to the CME principle. Oncological outcome was assessed as OS,
      disease-free survival (DFS) and cancer-specific survival (CSS), as well as time
      to recurrence (TTR), using Cox regression analysis. RESULTS: In-hospital
      mortality was 3.6%, 2.3% for laparoscopic surgery and 4.9% for open management.
      Significantly more patients in the open CME group developed complications in the
      short term (p < 0.001). Twelve or more lymph nodes were retrieved from 82.9%
      (208/251) of the specimens. Overall 3-year OS was 84.5%, DFS 77.4%, CSS 91.5% and
      TTR 86.8%. The surgical approach was not a significant predictor for any of the
      survival parameters. CONCLUSIONS: There was no survival difference between open
      and laparoscopic CME colonic resections, and the present OS improved from a
      previous OS from 2000.

PMID- 24022526
TI  - Asymmetric formation of tert-alkylamines from serinols by a dual function
      catalyst.
AB  - Consecutive intramolecular desymmetrization and kinetic resolution of 2
      substituted N-phenoxycarbonylserinols have been achieved in one-pot by a single
      chiral catalyst, bisox)-CuCl2, to form oxazolidinones with remarkable
      enantioselectivities (94-99% ee) as tert-alkylamine building blocks. The process
      culminates in a dual-function of the chiral catalyst. 

PMID- 24022527
TI  - Watch and wait approach following extended neoadjuvant chemoradiation for distal
      rectal cancer: are we getting closer to anal cancer management?
AB  - BACKGROUND: No immediate surgery (Watch and Wait) has been considered in select
      patients with complete clinical response after neoadjuvant chemoradiation to
      avoid postoperative morbidity and functional disorders after radical surgery.
      OBJECTIVE: The purpose of this study was to demonstrate the long-term results of
      patients who had a complete clinical response following an alternative
      chemoradiation regimen and were managed nonoperatively. DESIGN: This is a
      prospective study. SETTINGS: This study was conducted at a single center.
      PATIENTS: Seventy consecutive patients with T2-4N0-2M0 distal rectal cancer were
      studied. Neoadjuvant chemoradiotherapy included 54 Gy and 5
      fluorouracil/leucovorin delivered in 6 cycles every 21 days. Patients were
      assessed for tumor response at 10 weeks from radiation completion. Patients with
      incomplete clinical response were referred to immediate surgery. Patients with
      complete clinical response were not immediately operated on and were monitored.
      MAIN OUTCOME MEASURES: The primary outcomes measured were the initial complete
      clinical response rates after 10 weeks and the sustained complete clinical
      response rates after 12 months from chemoradiotherapy. RESULTS: One patient died
      during chemoradiotherapy because of cardiac complications. Forty-seven (68%)
      patients had initial complete clinical response. Of these, 8 developed local
      regrowth within the first 12 months of follow-up (17%). Thirty-nine sustained
      complete clinical response at a median follow-up of 56 months (57%). An
      additional 4 patients (10%) developed late local recurrences (>12 months of
      follow-up). Overall, 35 patients never underwent surgery (50%). LIMITATIONS: This
      study is limited by the short follow-up and small sample size. CONCLUSION:
      Extended chemoradiation therapy with additional chemotherapy cycles and 54 Gy of
      radiation may result in over 50% of sustained (>12 months) complete clinical
      response rates that may ultimately avoid radical rectal resection. Local failures
      occur more frequently during the initial 12 months of follow-up in up to 17% of
      cases, whereas late recurrences are less common but still possible, leading to
      50% of patients who never required surgery. Strict follow-up may allow salvage
      therapy in the majority of these patients (see Video, Supplemental Digital
      Content 1, http://links.lww.com/DCR/A113.).

PMID- 24022528
TI  - Long-term net survival in patients with colorectal cancer in France: an
      informative contribution of recent methodology.
AB  - BACKGROUND: Net survival, the survival that might occur if cancer was the only
      cause of death, is a major epidemiological indicator. Recent findings have shown
      that the classical methods used for the estimation of net survival from cancer
      registry data, referred as to "relative-survival methods," provided biased
      estimates. OBJECTIVES: The aim of this study was to provide, for the first time,
      long-term net survival rates for colorectal cancer by using a population-based
      digestive cancer registry. DESIGN: This study is a population-based cancer
      registry analysis. The recently proposed unbiased nonparametric Pohar-Perme
      estimator was used. PATIENTS: Overall, 14,715 colorectal cancers diagnosed
      between 1976 and 2005 and registered in the population-based digestive cancer
      registry of Burgundy (France) were included. MAIN OUTCOME MEASURES: The primary
      outcome measured was cancer net survival, ie, the survival that might occur if
      all risks of dying of other causes than cancer were removed RESULTS: : Ten-year
      net survival increased from 31% during the 1976 to 1985 period to 47% during the
      1986 to 1995 period and then leveled out (48% during the 1996-2005 period). There
      was a major improvement in 10-year net survival after resection for cure and for
      stage I to III. It was striking for stage III cancers, for which 10-year net
      survival increased from 21% (1976-1985) to 49% (1996-2005). The corresponding net
      survivals were 70% and 87% for stage I and 49% and 65% for stage II. These trends
      can be related to the decrease in operative mortality, the increase in the
      proportion of patients resected for cure, and the improvement in stage at
      diagnosis. They were mainly seen between 1976 and 1995, explaining why survival
      leveled out after 1995. LIMITATIONS: The study was limited by its retrospective
      and population-based nature. CONCLUSIONS: Further improvements for colorectal
      cancer management can be expected from more effective treatments and from the
      implementation of organized cancer screening.

PMID- 24022529
TI  - Predictive factors for early and late local toxicities in anal cancer treated by
      radiotherapy in combination with or without chemotherapy.
AB  - BACKGROUND: The treatment of anal cancer is based on concomitant radiotherapy and
      chemotherapy and is associated with a nonnegligible rate of local severe
      toxicities that can strongly impair the quality of life. OBJECTIVE: A
      retrospective analysis was performed to screen the following factors as potential
      predictive factors for local skin and digestive toxicities, and as potential
      prognostic factors for cumulative colostomy incidence: sex, age, tumor size,
      clinical T and N stage, circumferential extension, invasion of anal margin, HIV
      status, type of chemotherapy, and type of radiotherapy and dose delivered.
      METHODS: One hundred five patients in our database treated between January 2000
      and February 2010 met the eligibility criteria. RESULTS: Median follow-up was
      54.1 months (range, 1-133). Early and late severe local toxicities occurred in 33
      patients (31.4%) and 18 patients (17.1%). The 5-year cumulative rate of colostomy
      was 26.6%. Predictive factors for local severe early toxicities were as follows:
      clinical stage III/IV (p = 0.01), no brachytherapy boost (p = 0.003), and use of
      chemotherapy (p = 0.01). Only brachytherapy retained its independence in
      multivariate analysis (OR = 4.8 (1.4-16.3), p = 0.01). Human immunodeficiency
      virus positivity (p = 0.04) was the only predictive factor for late toxicities in
      univariate analysis; it was linked independently to the occurrence of ulcer (OR =
      0.1 (0.01-0.66), p = 0.01). Tumor size >=4 cm (p < 0.001) and occurrence of grade
      2 to 3 ulcers (p < 0.001) were correlated with greater cumulative colostomy
      incidence. CONCLUSIONS: In this cohort, nonuse of brachytherapy was an
      independent predictive factor for local acute toxicity. Human immunodeficiency
      virus positivity was the only predictive factor for local late toxicities and
      strongly influenced the onset of ulcer.

PMID- 24022530
TI  - Cumulative incidence of permanent stoma after sphincter preserving low anterior
      resection of mid and low rectal cancer.
AB  - BACKGROUND: Changes in the treatment of rectal cancer during the past decades
      have led to an increase in sphincter preservation with a consecutive decline in
      abdominoperineal resection rates. OBJECTIVE: The aim of this study was to analyze
      the cumulative incidence of permanent stoma in patients undergoing sphincter
      preserving resection of mid and low rectal cancer. DESIGN: This study is a
      retrospective analysis of prospectively collected data. SETTINGS: This study was
      conducted at a tertiary referral cancer hospital. PATIENTS: From 2003 to 2010,
      125 patients with primary mid and low rectal cancer who underwent sphincter
      preserving low anterior resection were included. MAIN OUTCOME MEASURES: The
      occurrence of a permanent stoma over time was investigated by using a Cox
      proportional hazards regression model and competing-risk models, with death as a
      competing risk. The risk factors were assessed by computing HRs and a Cox
      proportional hazards regression. RESULTS: After a median follow-up time of 61
      months (range, 22-113), 15 of 125 patients ended up with a permanent stoma,
      accounting for a 5-year cumulative incidence of 6% (95% CI, 4%-11%). The reasons
      for obtaining a permanent stoma were anastomotic leakage (60%, 9/15), intractable
      fecal incontinence (27%, 4/15), and local recurrence (13%, 2/15). The Cox
      proportional hazards regression identified anastomotic leakage (HR, 6.10; 95% CI,
      2.23-16.71; p = 0.0004) and coloanal anastomosis (HR, 4.31; 95% CI, 1.49-12.47; p
      = 0.007) as statistically significant risk factors. LIMITATIONS: Because of the
      small number of events in this sample, further investigations with a larger
      number of patients are required. Fecal incontinence was assessed by patient self
      reported data without the use of a validated score. CONCLUSION: The 5-year
      cumulative incidence of a permanent stoma was 6%. Anastomotic leakage and
      coloanal anastomosis were identified as risk factors. These details should be
      considered before sphincter-preserving surgery.

PMID- 24022531
TI  - Risk factors of poor functional results at 1-year after pseudocontinent perineal
      colostomy for ultralow rectal adenocarcinoma.
AB  - BACKGROUND: Pseudocontinent perineal colostomy is one of the techniques that
      helps recover the body image of patients undergoing abdominoperineal resection.
      This technique is rarely used internationally given its unknown functional
      results. OBJECTIVE: The study aimed to evaluate 1-year functional outcomes of
      perineal pseudocontinent colostomy and to determine the risk factors for "poor"
      functional results. DESIGN: This study is a retrospective interventional case
      series. SETTINGS: This study was conducted at a tertiary care university hospital
      and oncological center in Morocco. PATIENTS: From January 1993 to December 2007,
      149 patients underwent pseudocontinent perineal colostomy after abdominoperineal
      resection for low rectal adenocarcinoma. INTERVENTION: Pseudocontinent perineal
      colostomy was performed with the use of the Schmidt technique after
      abdominoperineal resection. MAIN OUTCOME MEASURES: One-year functional results
      were assessed according to the Kirwan classification system. Functional results
      were considered "poor" when the Kirwan score was C, D, or E. Univariable and
      multivariable analyses were used to evaluate the impact of age, sex, type of
      surgery, irrigation frequency, palpable muscular ring, concomitant
      chemoradiotherapy, stage, and perineal complications on functional results.
      RESULTS: One hundred forty-six patients were analyzed. According to the Kirwan
      system, the scores showed that 100 (68.5%) patients had "good" continence results
      (stage A-B) and 46 (31.5%) patients had altered functional results (stage C-D-E).
      With the exception of pelvic recurrences, no conversions from a perineal
      colostomy to an abdominal colostomy were performed for dissatisfactory functional
      results. In multivariate analysis, the only independent predictive factors of
      poor functional results were the occurrence of perineal complications (OR, 3.923;
      95% CI, 1.461-10.35; p = 0.007) and extended resection (OR, 3.03; 95% CI, 1.183
      7.750; p = 0.021) LIMITATION OF THE STUDY:: This study is an observational
      retrospective study on selected patients (mainly a young population).
      CONCLUSIONS: This study showed that perineal complications and extended resection
      are associated with poor functional results after pseudocontinent perineal
      colostomy. These data can help clinicians to better inform patients about the
      outcomes of this technique and to assist them in choosing the right
      reconstruction technique after abdominoperineal resection.

PMID- 24022532
TI  - Preoperative oral antibiotics and intravenous antimicrobial prophylaxis reduce
      the incidence of surgical site infections in patients with ulcerative colitis
      undergoing IPAA.
AB  - BACKGROUND: The usefulness of preoperative oral antibiotics for the prevention of
      surgical site infection in elective colorectal surgery remains controversial.
      OBJECTIVE: This study aimed to investigate the effects of oral antimicrobial
      prophylaxis in addition to intravenous antimicrobial prophylaxis on patients with
      ulcerative colitis undergoing restorative proctocolectomy. DESIGN: This study was
      a randomized, nonblinded, single-center clinical trial. SETTING: This study was
      conducted between July 1, 2006, and April 30, 2009, at Hyogo College of Medicine.
      PATIENTS: Two hundred patients with ulcerative colitis scheduled to undergo
      restorative proctocolectomy with IPAA with an open approach were randomly
      assigned to either group A or B (n = 100). Combined use of preoperative oral
      antibiotics and intravenous antimicrobial prophylaxis were given to group A, and
      intravenous antimicrobial prophylaxis alone was given to group B. INTERVENTIONS:
      Patients in group A received oral antibiotics the day before surgery (500 mg of
      kanamycin and 500 mg of metronidazole at 2:00 P.M., 3:00 P.M., and 9:00 P.M.),
      whereas those in group B did not. All patients underwent preoperative mechanical
      bowel preparation, and intravenous antimicrobial prophylaxis with second
      generation cephalosporin was given for 24 hours. MAIN OUTCOME MEASURES: The
      primary end point of this study was the incidence of overall surgical site
      infection according to intention-to-treat analysis. RESULTS: The incidence of
      overall surgical site infection was significantly lower in group A (6/97
      patients, 6.1%) than in group B (22/98 patients, 22.4%) (p = 0.0024). In
      multivariate analysis, the administration of oral antibiotics (OR, 0.178; 95% CI,
      0.057-0.552; p = 0.003) and ASA score >=3 (OR, 5.343; 95% CI, 1.595-17.891; p =
      0.007) were independent risk factors for surgical site infection. LIMITATIONS:
      This study is limited because of its open-label nature. CONCLUSIONS: Combined
      oral and intravenous antimicrobial prophylaxis in patients with ulcerative
      colitis undergoing restorative proctocolectomy with IPAA contributed to the
      prevention of surgical site infection.

PMID- 24022533
TI  - Risk factors for surgical site infection and association with infliximab
      administration during surgery for Crohn's disease.
AB  - BACKGROUND: Preoperative infliximab treatment may influence postoperative
      infectious complications in patients with Crohn's disease. OBJECTIVE: The aim of
      this study was to identify predictors of surgical site infection after surgery
      for Crohn's disease and evaluate the effects of preoperative infliximab
      administration. DESIGN: We performed a prospective surveillance and review of
      surgical site infections. SETTINGS: This study was conducted in the Surgical
      Department of Hyogo College of Medicine. PATIENTS: A total of 405 consecutive
      patients with Crohn's disease who underwent abdominal surgery between January
      2008 and December 2011 were included. MAIN OUTCOME MEASURES: Infection was
      diagnosed by the infection control team. The possible risk factors were analyzed
      by using logistic regression analyses to determine their predictive significance.
      RESULTS: Within the patient population, 20% of patients received infliximab, and
      60% had penetrating disease. The median duration from the last infliximab
      infusion to surgery was 43 days (range, 4-80). The overall incidence of surgical
      site infection was 27%. The incidence of incisional surgical site infection was
      18%, and the organ/space surgical site infection rate was 8%. In the multivariate
      analysis, proctectomy was the highest risk factor for all surgical site infection
      (OR, 3.4-11.8; p < 0.01). The administration of preoperative infliximab was not a
      risk factor for surgical site infection. By contrast, there was a significantly
      reduced risk of incisional surgical site infection in patients with penetrating
      disease who received infliximab (OR, 0.1; p < 0.01). LIMITATIONS: This study was
      a cohort study and not a randomized trial. The data analyses were performed for
      surgical site infections but not for other infectious complications. CONCLUSIONS:
      Proctectomy was a high-risk factor for surgical site infection in patients with
      Crohn's disease. The administration of preoperative infliximab was not a risk
      factor for surgical site infection.

PMID- 24022534
TI  - Topical tacrolimus therapy for antibiotic-refractory pouchitis.
AB  - BACKGROUND: Pouchitis is the most common complication after restorative
      proctocolectomy for ulcerative colitis, and it leads to pouch failure. The
      administration of oral antibiotics is the main treatment for pouchitis; however,
      in some cases, antibiotic-refractory pouchitis may develop, which requires
      further medical therapy. OBJECTIVE: We investigated the applicability of topical
      tacrolimus for refractory pouchitis. DESIGN: We performed a prospective pilot
      study. The study protocols were registered with the University Hospital Medical
      Information Network Clinical Trials Registry, 000006658. SETTING: This study was
      conducted in the Surgical Department of Hyogo College of Medicine. PATIENTS:
      Patients with antibiotic-refractory pouchitis were treated for 8 weeks with a
      tacrolimus enema. MAIN OUTCOME MEASURES: The efficacy was assessed by comparing
      Pouchitis Disease Activity Index scores. Safety was assessed by measuring whole
      blood tacrolimus trough levels. RESULTS: Ten patients with refractory pouchitis
      were enrolled. No severe adverse events occurred. The mean scores decreased from
      15.9 +/- 0.8 to 7.8 +/- 0.8 during 8 weeks of treatment (p < 0.01). Specifically,
      the clinical symptom, endoscopic finding, and histological finding subscores
      decreased to 0.8 +/- 0.6, 3.9 +/- 0.2, and 2.9 +/- 0.4. Nine patients recovered
      from their clinical symptoms, and 3 patients recovered from pouchitis.
      LIMITATIONS: This small study was neither blinded nor randomized. CONCLUSIONS:
      This study demonstrates that the use of topical tacrolimus for the treatment of
      refractory pouchitis is safe and effective in the short term for clinical
      symptoms. Although complete endoscopic healing was not achieved, this treatment
      may have early rescue efficacy in the treatment of antibiotic-refractory
      pouchitis.

PMID- 24022536
TI  - Neurological outcome following resection of benign presacral neurogenic tumors
      using a nerve-sparing technique.
AB  - BACKGROUND: Benign presacral nerve sheath tumors represent up to 10% of all
      presacral tumors. Limited data exist regarding the impact of the surgical
      technique on neurological outcomes following resection. OBJECTIVE: The aim of
      this study was to test our hypothesis that a nerve-sparing resection technique
      results in the improvement of preoperative neurological dysfunction and minimal
      postoperative neurological morbidity. DESIGN: This study is a case series of all
      patients with benign neurogenic presacral tumors operated on by the same 2
      surgeons between 2004 and 2010 at our institution. SETTINGS: This study was
      performed at a tertiary care center. PATIENTS: Adult patients with benign
      presacral neurogenic tumors who underwent a nerve-sparing resection were
      included. MAIN OUTCOME MEASURES: Postoperative urogenital, anorectal, and lower
      extremity neurological functions were analyzed. RESULTS: Seventeen patients were
      identified with a mean age of 40 years; 14 were women. Preoperatively, 13
      patients had symptoms from neurological dysfunction or presumed mass effect of
      the tumor. The mean tumor size was 7.4 cm. The pathology was a schwannoma in 12
      patients and neurofibroma in 5 patients. Mortality was nil, and 30-day morbidity
      was noted in 3 patients (hemorrhage, ileus, acute respiratory distress syndrome,
      deep vein thrombosis, and transient foot drop). Mean follow-up was 36 months. Of
      the 13 symptomatic patients, 7 achieved complete resolution of symptoms and 5 had
      improved, but persistent symptoms. None of the 4 asymptomatic patients developed
      postoperative neurological dysfunction. LIMITATIONS: Small sample size was a
      limitation of this study. CONCLUSIONS: With the use of a nerve-sparing technique,
      function-preserving resection can be safely completed with an overall improvement
      in symptoms.

PMID- 24022535
TI  - Utilization and safety of sodium hyaluronate-carboxymethylcellulose adhesion
      barrier.
AB  - BACKGROUND: Little is known about the use and toxicity of antiadhesion substances
      such as sodium hyaluronate-carboxymethylcellulose. OBJECTIVE: We analyzed the
      patterns of use and safety of sodium hyaluronate-carboxymethylcellulose in
      patients undergoing colectomy and gynecologic surgery. DESIGN: This is a
      retrospective cohort study. SETTING: This study covered hospitals nationwide.
      PATIENTS: All patients in the Premier Perspective database who underwent
      colectomy or hysterectomy from 2000 to 2010 were included in the analyses. MAIN
      OUTCOME MEASURE: Hyaluronate-carboxymethylcellulose use was determined by billing
      codes. For the primary outcome, we used hierarchical mixed-effects logistic
      regression models to determine the factors associated with the use of hyaluronate
      carboxymethylcellulose, whereas a propensity score-matched analysis was used to
      secondarily assess the association between hyaluronate-carboxymethylcellulose use
      and toxicity (abscess, bowel and wound complications, peritonitis). RESULTS: We
      identified 382,355 patients who underwent hysterectomy and 267,368 who underwent
      colectomy. For hysterectomy, hyaluronate-carboxymethylcellulose use was 5.0%
      overall, increasing from 1.1% in 2000 to 9.8% in 2010. Hyaluronate
      carboxymethylcellulose was used in 8.1% of those who underwent colectomy and
      increased from 6.2% in 2000 to 12.4% in 2010. The year of diagnosis and procedure
      volume of the attending surgeon were the strongest predictors of hyaluronate
      carboxymethylcellulose use. After matching and risk adjustment, hyaluronate
      carboxymethylcellulose use was not associated with abscess formation (1.5% vs
      1.5%) (relative risk = 0.97; 95% CI, 0.84-1.12) in those who underwent
      hysterectomy. A patient receiving hyaluronate-carboxymethylcellulose had a 13%
      increased risk of abscess (17.4% vs 15.0%) (relative risk = 1.13; 95% CI, 1.08
      1.17) after colectomy. LIMITATIONS: This was an observational study. CONCLUSION:
      Hyaluronate-carboxymethylcellulose use has increased over the past decade for
      colectomy and hysterectomy. Although there is no association between hyaluronate
      carboxymethylcellulose use and abscess following hysterectomy, hyaluronate
      carboxymethylcellulose use was associated with a small increased risk of abscess
      after colectomy.

PMID- 24022537
TI  - Robotic transanal endoscopic microsurgery: technical details for the lateral
      approach.
AB  - BACKGROUND: Transanal endoscopic microsurgery is a minimally invasive approach
      reserved for the resection of selected rectal tumors. However, this approach is
      technically demanding. Although robotic technology may overcome the limitations
      of this approach, the system can be difficult to dock, especially in the
      lithotomy position. OBJECTIVE: The study aim is thus to report the technical
      details of robotic transanal endoscopic microsurgery with the use of a lateral
      approach. DESIGN AND SETTINGS: This study is a prospective evaluation of robotic
      transanal endoscopic microsurgery in a single tertiary institution, under a
      protocol approved by our local ethics committee. INTERVENTION: Patients underwent
      a routine mechanical bowel preparation and were placed in the left or right
      lateral position according to the tumor location. A circular anal dilatator was
      used together with the glove port technique. The robotic system was then docked
      over the hip. A 30 degrees  optic and 2 articulated instruments were used with an
      additional assistant trocar. The tumor excision was realized with an atraumatic
      grasper and an articulated cautery hook, and the defect was closed with barbed
      continuous stiches in each case. MAIN OUTCOME MEASURE: The primary outcome was
      the safety and feasibility of the procedure. RESULTS: Three patients underwent a
      robotic transanal endoscopic microsurgery with the use of the lateral approach.
      Mean operative time was 110 minutes, including 20 minutes for the docking of the
      robot. There was 1 intraoperative complication (a pneumoperitoneum without
      intraabdominal lesion) and no postoperative complications. Mean hospital stay was
      3 days. Margins were negative in all the cases. LIMITATIONS: The study was
      limited by the small number of patients. CONCLUSION: Robotic transanal endoscopic
      microsurgery with use of the lateral approach is feasible and may facilitate the
      local resection of small lesions of the mid and lower rectum. It might assume an
      important place in sphincter-preserving surgery, especially for selected and
      early rectal cancer (see Video, Supplemental Digital Content 1,
      http://links.lww.com/DCR/A114).

PMID- 24022538
TI  - C-reactive protein and procalcitonin as predictors of anastomotic leak.

PMID- 24022539
TI  - The authors reply.

PMID- 24022540
TI  - Comments on decision analysis for patients with T1 adenocarcinoma of the low
      rectum.

PMID- 24022543
TI  - Radiation exposure and safety for the electrophysiologist.
AB  - This review attempts to give practical advice for invasive electrophysiologists
      on personal radiation protection. Applying all measures of the "As low as
      reasonably achievable" ALARA concept should be a daily and indeed routine
      practice for all staff in the electrophysiology laboratory. A substantial number
      of technical options have been recently introduced which may enable the physician
      to lower the total radiation exposure significantly, but all require a
      substantial learning curve. Using these measures can arrive at very low or indeed
      close to ZERO fluoroscopy exposure even in complex ablation cases. 

PMID- 24022544
TI  - Is there a need for "triple therapy"? Role of anticoagulation with dual
      antiplatelet therapy in acute coronary syndromes (ATLAS Study & TRAP Study).
AB  - In the past two decades there has been a succession of advances in the
      development of anticoagulant and antiplatelet therapies to be used in the
      treatment of ACS. Despite optimal dual antiplatelet therapy, nearly 10-12 % of
      patients still face a risk of death or myocardial infarction one year following
      PCI. This large residual risk provides the impetus for the development of more
      effective strategies. Dual pathway regimens that combine antiplatelets (aspirin
      and a thienopyridine), along with an anticoagulant such as rivaroxaban may prove
      to be a therapeutic option in patients with ACS. 

PMID- 24022545
TI  - Improving the success rate of protein crystallization by random microseed matrix
      screening.
AB  - Random microseed matrix screening (rMMS) is a protein crystallization technique
      in which seed crystals are added to random screens. By increasing the likelihood
      that crystals will grow in the metastable zone of a protein's phase diagram,
      extra crystallization leads are often obtained, the quality of crystals produced
      may be increased, and a good supply of crystals for data collection and soaking
      experiments is provided. Here we describe a general method for rMMS that may be
      applied to either sitting drop or hanging drop vapor diffusion experiments,
      established either by hand or using liquid handling robotics, in 96-well or 24
      well tray format. 

PMID- 24022546
TI  - Integrated care for homeless people in hospital: an acid test for the NHS?

PMID- 24022547
TI  - Mastectomies of healthy, contralateral breasts in patients with breast cancer.

PMID- 24022549
TI  - 'The patient is medically cleared'.
AB  - It is standard practice for psychiatric nurses and junior doctors working in
      emergency departments to ask that patients be 'medically cleared' before
      psychiatric admission or even assessment. However, there is a lack of agreement
      over what this process should entail. 

PMID- 24022550
TI  - Sleep-induced hypoxaemia in patients with chronic obstructive pulmonary disease.
AB  - Patients with moderate or severe chronic obstructive pulmonary disease run a high
      risk of developing sleep-induced hypoxaemia, because of alveolar hypoventilation
      and ventilation-perfusion mismatch. This article looks at the prevalence,
      significance and treatment of sleep-induced hypoxaemia in chronic obstructive
      pulmonary disease. 

PMID- 24022551
TI  - New developments in cardiac resynchronization therapy.
AB  - Cardiac resynchronization therapy significantly reduces mortality and morbidity
      in patients with heart failure and ventricular dyssynchrony. This is a dynamic
      field with some exciting recent advances, and these future directions are
      discussed in this review. 

PMID- 24022552
TI  - Expanding organ donation in the UK: ethical, moral and logistical dilemmas.
AB  - In the UK, three patients die every day waiting for an organ transplant. Despite
      there being 18.7 million donors currently registered in the UK, donation rates
      remain low. This review discusses the legal, ethical and social aspects of organ
      donation in the UK, and looks at some controversial solutions adopted in other
      countries. 

PMID- 24022553
TI  - Management of lower urinary tract symptoms in men.
AB  - Lower urinary tract symptoms in men are common, increase with age and can become
      bothersome, causing significant morbidity such as urinary retention or the need
      for surgery. This article outlines how to assess a man with lower urinary tract
      symptoms and when to refer to a specialist, and summarizes current treatment
      options. 

PMID- 24022554
TI  - Improving the quality of prescribing in the emergency department.
AB  - Prescribing errors are common and can have a significant negative impact on
      patients. This article presents an audit and intervention which aimed to improve
      prescribing safety, documentation and handover in the emergency department. The
      authors identified shortcomings in the emergency department drug chart, which
      were subsequently confirmed by audit. To address these shortcomings, a new drug
      chart was designed and introduced, before repeating the audit. This intervention
      resulted in significantly more frequent documentation of key aspects of the
      prescription including date and time, and rate and volume for infusions. This low
      cost intervention is applicable to other emergency department settings. 

PMID- 24022555
TI  - An unusual cause of hemiplegia in a 28-year-old woman.

PMID- 24022556
TI  - Pulmonary carcinoid presenting with cavitating lung infection and oligometastatic
      mediastinal disease.

PMID- 24022557
TI  - Paraneoplastic systemic lupus erythematosus associated with papillary thyroid
      carcinoma.

PMID- 24022558
TI  - Iliacus pyomyositis.

PMID- 24022559
TI  - Ricin poisoning: a case of internet-assisted parasuicide.

PMID- 24022560
TI  - Sudden apparent worsening of diabetic retinopathy leading to a diagnosis of
      chronic myeloid leukaemia.
AB  - A 65-year-old woman with well-controlled type 2 diabetes presented with a sudden
      decrease in visual acuity bilaterally (right eye 6/60, left eye 6/18). 

PMID- 24022561
TI  - Reginald Fitz: father of appendicitis.

PMID- 24022562
TI  - MB/PhD: don't forget the 'BS'.

PMID- 24022563
TI  - Financially supporting your grown-up children.
AB  - At this time of year, many parents are concerned about how they are going to fund
      their child's school or university education. However, paying for children does
      not always stop once they graduate. 

PMID- 24022565
TI  - Should ketamine be used as an induction agent in traumatic brain injury?

PMID- 24022566
TI  - Oral L-arginine modulates blood lactate and interleukin-6 after exercise in HIV
      infected men.
AB  - The acute administration of L-arginine (L-arg), a nitric oxide (NO) precursor,
      reduces lactate (LAC) concentration after exercise in healthy individuals. Lower
      concentration of L-arg may enhance the action of some inflammatory cytokines in
      HIV-1 infected patients. We tested the hypothesis that acute L-arg administration
      may reduce post-exercise blood LAC and inflammatory cytokines levels in HIV
      infected patients. 10 HIV-infected men performed 2 maximal incremental
      cardiopulmonary exercise tests, separated by one week. 30 min before each test,
      patients received oral placebo or 20 g of L-arg, in random order. Blood LAC,
      tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10
      (IL-10) were measured before and up to 60 min after exercise. L-arg
      administration had no significant effect on exercise performance. Compared to
      placebo, L-arg administration reduced maximal post-exercise blood LAC from 8.7+/
      0.6 to 6.9+/-0.4 mmol.L-1 (p<0.05). L-arg administration had no significant
      effect on TNF-alpha or IL-10 concentrations, but increased post-exercise IL-6
      (placebo=19+/-3pg.mL-1; L-arg=63+/-8 pg.mL-1; p<0.05). In HIV-1 infected men,
      acute administration of L-arg reduces post-exercise blood LAC and increases IL-6
      levels, suggesting the activation of the L-arg-NO pathway, with possible anti
      inflammatory consequences. 

PMID- 24022567
TI  - Associations of maximal strength and muscular endurance with cardiovascular risk
      factors.
AB  - The aim was to study the associations of maximal strength and muscular endurance
      with single and clustered cardiovascular risk factors. Muscular endurance,
      maximal strength, cardiorespiratory fitness and waist circumference were measured
      in 686 young men (25+/-5 years). Cardiovascular risk factors (plasma glucose,
      serum high- and low-density lipoprotein cholesterol, triglycerides, blood
      pressure) were determined. The risk factors were transformed to z-scores and the
      mean of values formed clustered cardiovascular risk factor. Muscular endurance
      was inversely associated with triglycerides, s-LDL-cholesterol, glucose and blood
      pressure (beta=-0.09 to - 0.23, p<0.05), and positively with s-HDL cholesterol
      (beta=0.17, p<0.001) independent of cardiorespiratory fitness. Muscular endurance
      was negatively associated with the clustered cardiovascular risk factor
      independent of cardiorespiratory fitness (beta=-0.26, p<0.05), whereas maximal
      strength was not associated with any of the cardiovascular risk factors or the
      clustered cardiovascular risk factor independent of cardiorespiratory fitness.
      Furthermore, cardiorespiratory fitness was inversely associated with
      triglycerides, s-LDL-cholesterol and the clustered cardiovascular risk factor
      (beta=-0.14 to - 0.24, p<0.005), as well as positively with s-HDL cholesterol
      (beta=0.11, p<0.05) independent of muscular fitness. This cross-sectional study
      demonstrated that in young men muscular endurance and cardiorespiratory fitness
      were independently associated with the clustering of cardiovascular risk factors,
      whereas maximal strength was not. 

PMID- 24022568
TI  - Sport injuries aligned to peak height velocity in talented pubertal soccer
      players.
AB  - In young athletes, demands of sports are superimposed on normal growth and
      maturation. It has been suggested that this causes a temporarily increased
      vulnerability for injuries. We followed 26 talented soccer players (mean age
      11.9+/-0.84 years) longitudinally for 3 years around their adolescent growth
      spurt, called Peak Height Velocity, to identify differences in number of
      traumatic and overuse injuries and days missed due to injuries. Peak Height
      Velocity was calculated according to the Maturity Offset Protocol. The number of
      injuries was calculated for each player per year. A repeated measurement analysis
      showed that athletes had significantly more traumatic injuries in the year of
      Peak Height Velocity (1.41) than in the year before Peak Height Velocity (0.81).
      A moderate effect size of 0.42 was found for the difference in number of overuse
      injuries per player per year before (0.81) and after Peak Height Velocity (1.41),
      respectively. Finally, a moderate effect size of 0.55 was found for difference
      between days missed due to injuries before (7.27 days per player per year) and
      during Peak Height Velocity (15.69 days per player per year). Adolescent growth
      spurt seems to result in increased vulnerability for traumatic injuries.
      Afterwards athletes seem to be susceptible to overuse injuries. 

PMID- 24022569
TI  - Effect of aerobic exercise on miRNA-TLR4 signaling in atherosclerosis.
AB  - Toll-like receptor 4 (TLR4)-tumor necrosis factor receptor 6 (TRAF6) signaling is
      activated in atherosclerosis (AS), inducing inflammatory mediators. Because miR
      146a, a TLR4 microRNA (miRNA), can regulate TLR4 signaling during inflammatory
      responses, this study investigated the effects of aerobic exercise on TLR4
      targeted miRNAs in AS. Apolipoprotein E-null mice fed a high-fat diet for 12
      weeks were separated into 3 groups: (i) no treatment (AS), (ii) statin treatment
      (AD), or (iii) aerobic exercise (AE). Plaques and foam cells were observed in the
      untreated control and statin groups, respectively, but not in the AE group.
      Reduced angiotensin II (Ang II) and endothelin 1 (ET1) levels were observed in
      the AE group. Both treatment groups significantly altered the expression of
      inflammatory cytokine expression and reduced vascular TLR4 levels. Increased miR
      146a and miR-126 and reduced miR-155 levels were observed in both treatment
      groups (all, P<0.001). miR-146a interacted with the 3' untranslated region of the
      TRAF6 gene, reducing its expression. Thus, aerobic exercise and statins may
      induce miR-146a expression, thereby reducing vascular TRAF and TLR4 signaling and
      vascular inflammatory injury in AS. Further analysis of this pathway may provide
      insight into the protective effects of aerobic exercise on vascular disease as
      well as new therapeutic targets. 

PMID- 24022570
TI  - Improved gross efficiency during long duration submaximal cycling following a
      short-term high carbohydrate diet.
AB  - To assess the effect of dietary manipulation on gross efficiency (GE), 15 trained
      male cyclists completed 3*2 h tests at submaximal exercise intensity (60% Maximal
      Minute Power). Using a randomized, crossover design participants consumed an
      isoenergetic diet (~4 000 kcal.day-1) in the 3 days preceding each test, that was
      either high in carbohydrate (HighCHO, [70% of the total energy derived from
      carbohydrate, 20% fat, 10% protein]), low in carbohydrate (LowCHO, [70% fat, 20%
      carbohydrate, 10% protein]) or contained a moderate amount of carbohydrate
      (ModCHO, [45% carbohydrate, 45% fat, 10% protein]). GE along with blood lactate
      and glucose were assessed every 30 min, and heart rate was measured at 5 s
      intervals throughout. Mean GE was significantly greater following the HighCHO
      than the ModCHO diet (HighCHO=20.4%+/-0.1%, ModCHO=19.6+/-0.2%; P<0.001).
      Additionally, HighCHO GE was significantly greater after 25 min (P=0.015) and 85
      min (P=0.021) than in the LowCHO condition. Heart rate responses in the HighCHO
      condition were significantly lower than during the LowCHO tests (P=0.005). Diet
      had no effect on blood glucose or lactate (P>0.05). This study suggests that
      before the measurement of gross efficiency, participants' diet should be
      controlled and monitored to ensure the validity of the results obtained. 

PMID- 24022571
TI  - Psychological influences predict recovery following exercise induced shoulder
      pain.
AB  - Predicting recovery following muscle injury can be difficult because it involves
      consideration of multiple factors. Our objective was to determine if
      psychological factors, sex, and peak pain and disability ratings could be
      predictive of delayed recovery following induced muscle injury. Healthy untrained
      volunteers (n=126; M:F 51:75) underwent a concentric/eccentric isokinetic
      exercise protocol on their dominant shoulder to induce fatigue, with individuals
      who reported pain (>0/10) at 96 h being classified as "not recovered".
      Individuals experiencing pain at 48 h were more likely not to be recovered
      (O.R.=1.62, p<0.001). Additionally, individuals with higher scores in pain
      catastrophizing at 48 h were more likely to experience pain at 96 h (O.R.=1.06,
      p<0.001). Pain duration (in days) was associated with pain scores at 48 h
      (beta=0.385, p<0.001) and baseline anxiety (beta=0.220, p=0.007). Fear of
      movement/re-injury at 96 h was found to be associated with pain catastrophizing
      at 48 h (beta=0.537, p<0.001) and baseline levels of fear of pain (beta=0.217,
      p=0.004). This study provides preliminary evidence that higher pain levels and
      pain catastrophizing following acute muscle injury are associated with poor
      recovery, higher fear of movement/re-injury and longer pain duration. 

PMID- 24022572
TI  - Exercise sensitizes skeletal muscle to extracellular ATP for IL-6 expression in
      mice.
AB  - Active skeletal muscle synthesizes and releases interleukin-6 (IL-6), which plays
      important roles in the organism's adaptation to exercise. Autocrine/paracrine ATP
      signaling has been shown to modulate IL-6 expression. The aim of this study was
      to determine whether a period of physical activity modifies the ATP-induced IL-6
      expression. BalbC mice were either subject to 5 weeks voluntary wheel running
      (VA) or kept sedentary (SED). Flexor digitorum brevis muscles were dissected,
      stimulated with different ATP concentrations (0-100 MUM) and IL-6 mRNA levels
      were measured using qPCR. ATP evoked a concentration-dependent rise in IL-6 mRNA
      in both SED and VA mice. VA mice however, had significantly higher ATP
      sensitivity (pD2 pharmacological values: VA=5.58+/-0.02 vs. SED=4.95+/-0.04,
      p<0.05). Interestingly, in VA mice we observed a positive correlation between the
      level of physical activity and the IL-6 mRNA increase following fiber stimulation
      with 10 MUM ATP. In addition, there were lower P2Y2- and higher P2Y14-receptor
      mRNA levels in skeletal muscles of VA compared to SED mice, showing plasticity of
      nucleotide receptors with exercise. These results suggest that exercise increases
      skeletal muscle ATP sensitivity, a response dependent on the level of physical
      activity performed. This could have an important role in the mechanisms
      controlling skeletal muscle adaptation to exercise and training. 

PMID- 24022573
TI  - Inferior muscularity of the rectus femoris to vasti in varsity oarsmen.
AB  - The purpose of this study was to examine the morphological profiles of 4
      constituents (vastus lateralis, vastus medialis, vastus intermedius and rectus
      femoris) of the quadriceps femoris in oarsmen through comparison with non
      athletes. T1-weigheted magnetic resonance (MR) images of the thigh were obtained
      from 14 oarsmen and 19 non-athlete men. From the MR images, serial anatomical
      cross-sectional areas (ACSAs) and muscle volume of each muscle were determined.
      The muscle volume of the total quadriceps femoris, vastus lateralis, vastus
      medialis and vastus intermedius were significantly larger in the oarsmen than in
      the non-athlete men, whereas that of the rectus femoris was comparable for the 2
      groups. The portion of the rectus femoris as a percentage of total quadriceps
      femoris volume was significantly higher in the non-athlete men than in the
      oarsmen, and vice versa for the vastus lateralis. The proximal-to-distal and
      middle-to-distal ACSA ratios in each muscle did not differ between the 2 groups.
      The present results indicate inferior muscular hypertrophy of the rectus femoris
      compared to the vasti in oarsmen, and that the vasti are equally hypertrophied
      along their lengths. This may be due to muscle-specific adaptation to the rowing
      exercise. 

PMID- 24022574
TI  - High agreement between laboratory and field estimates of critical power in
      cycling.
AB  - The purpose of this study was to investigate the level of agreement between
      laboratory-based estimates of critical power (CP) and results taken from a novel
      field test. Subjects were fourteen trained cyclists (age 40+/-7 yrs; body mass
      70.2+/-6.5 kg; VO2max 3.8+/-0.5 L . min-1). Laboratory-based CP was estimated
      from 3 constant work-rate tests at 80%, 100% and 105% of maximal aerobic power
      (MAP). Field-based CP was estimated from 3 all-out tests performed on an outdoor
      velodrome over fixed durations of 3, 7 and 12 min. Using the linear work limit
      (Wlim) vs. time limit (Tlim) relation for the estimation of CP1 values and the
      inverse time (1/t) vs. power (P) models for the estimation of CP2 values, field
      based CP1 and CP2 values did not significantly differ from laboratory-based
      values (234+/-24.4 W vs. 234+/-25.5 W (CP1); P<0.001; limits of agreement [LOA], 
      10.98-10.8 W and 236+/-29.1 W vs. 235+/-24.1 W (CP2); P<0.001; [LOA], -13.88-17.3
      W. Mean prediction errors for laboratory and field estimates were 2.2% (CP) and
      27% (W'). Data suggest that employing all-out field tests lasting 3, 7 and 12 min
      has potential utility in the estimation of CP.

PMID- 24022575
TI  - The 3-min test does not provide a valid measure of critical power using the SRM
      isokinetic mode.
AB  - Recent datas suggest that the mean power over the final 30 s of a 3-min all-out
      test is equivalent to Critical Power (CP) using the linear ergometer mode. The
      purpose of the present study was to identify whether this is also true using an
      "isokinetic mode". 13 cyclists performed: 1) a ramp test; 2) three 3-min all-out
      trials to establish End Power (EP) and work done above EP (WEP); and 3) 3
      constant work rate trials to determine CP and the work done above CP (W') using
      the work-time (=CP1/W'1) and 1/time (=CP2/W'2) models. Coefficient of variation
      in EP was 4.45% between trials 1 and 2, and 4.29% between trials 2 and 3. Limits
      of Agreement for trials 1-2 and trials 2-3 were -2+/-38 W. Significant
      differences were observed between EP and CP1 (+37 W, P<0.001), between WEP and
      W'1(-6.2 kJ, P=0.001), between EP and CP2 (+31 W, P<0.001) and between WEP and
      W'2 (-4.2 kJ, P=0.006). Average SEE values for EP-CP1 and EP-CP2 of 7.1% and 6.6%
      respectively were identified. Data suggest that using an isokinetic mode 3-min
      all-out test, while yielding a reliable measure of EP, does not provide a valid
      measure of CP. 

PMID- 24022576
TI  - Physical and technical comparisons between various-sided games within
      professional soccer.
AB  - This study compared the technical activity and physical movements of various
      sided games within professional soccer. It also examined the test-retest
      reliability of sided games using various numbers of players. 10 elite male
      players from a Scottish Premier League performed small- (SSGs: 4 vs. 4), medium-
      (MSGs: 5 vs. 5 to 8 vs. 8) and large- (LSGs: 9 vs. 9 to 11 vs. 11) sided games
      each lasting for 3*5 min. Results show significant physical differences (p<0.05)
      between SSGs, MSGs and LSGs for most of the variables measured. It was shown that
      SSGs induce a significantly faster playing speed when compared to MSGs and LSGs
      (150.5 vs. 108.3 vs. 120.4 m.min-1, p<0.01) but significantly less (p<0.01)
      repeated high-intensity efforts (0.88 vs. 4.40 m), high-intensity running (7 vs.
      39 m) and sprint distance (0 vs. 11 m) when compared to LSGs. Findings also
      revealed significant differences (p<0.05) between SSGs, MSGs and LSGs in
      technical demands (passes, dribbles, shots, headers). High levels of
      reproducibility (ICC=0.99) were yielded when using the same-sided games, pitch
      sizes and possession rules. This study provided information on different-sided
      games to facilitate its use as part of a periodised weekly structure. 

PMID- 24022577
TI  - Standardization of resistance exercise training: effects in diabetic
      ovariectomized rats.
AB  - This study was carried out with a 3-fold aim: 1) to standardize a maximal load
      test (MLT) on ladders for prescription of resistance exercise training (RET) in
      rats, 2) to prescribe moderate-intensity RET based on this MLT and 3) to test the
      effect of this RET in diabetic ovariectomized rats. Female Wistar rats were
      divided into control (C), diabetic ovariectomized sedentary (DOS) and trained
      (DOT) groups. The MLT was standardized with increased load applied to the rat
      tail for each climb, and blood lactate was measured to identify lactate threshold
      in C rats. MLT was applied in the 1st, 4th and 8th week of the protocol. After 8
      weeks of RET, the arterial pressure was directly recorded. DOS group reduced
      performance in MLT, body weight, left ventricular, plantar and soleus muscles
      mass (vs. C). DOT rats showed an improvement in MLT associated with plantar
      muscle mass increased (vs. C and DOS), with attenuation of hypotension and
      bradycardia (vs. DOS). In conclusion, the results provide a useful method for
      determining the maximal load and applying RET in rats. Moreover, this study
      showed that moderate intensity RET improves hemodynamic status in diabetic
      ovariectomized rats, thereby reinforcing the role of RET in diabetes management. 

PMID- 24022578
TI  - Limited benefit of Fatmax-test to derive training prescriptions.
AB  - The intensity that elicits maximal fat oxidation (Fatmax) is recommended for
      training fat metabolism. However, it remains unclear whether Fatmax leads to the
      highest fat oxidation rates during prolonged exercise. It was hypothesized that
      there are no differences in fat oxidation rates among 3 different exercise
      intensities. Therefore, fat metabolism was compared among 1-h constant load tests
      at Fatmax, a higher and a lower intensity. A cohort of 16 male cyclists (28+/-6
      yrs, BMI: 22.5+/-1.2 kg/m2; n=8 with maximal oxygen uptake [VO2max] of 50-60
      ml/min/kg [ET]; n=8 with VO2max>60 ml/min/kg [HET]) completed a maximal
      incremental cycling test, a submaximal incremental Fatmax-test and, thereafter,
      three 1-h constant-load tests in randomized order at Fatmax, one exercise stage
      below (LOW) and one above (HIGH). LOW, Fatmax and HIGH were performed at 52+/-13,
      60+/-13 and 70+/-12% VO2max. Heart rate and blood lactate were significantly
      different (p<0.001). However, the fat oxidation rate showed no difference
      (p=0.61). This was also true within each subgroup (ET: p=0.69, HET p=0.61). In
      conclusion, the fat oxidation rate of endurance trained cyclists shows no
      difference between 1-h constant load exercise bouts at about 50-70% VO2max. The
      precision and necessity of Fatmax-tests for controlling the training of fat
      oxidation are therefore debatable. 

PMID- 24022579
TI  - A redox-triggered structural rearrangement in an iodate-templated
      polyoxotungstate cluster cage.
AB  - The new tungstatoiodate, alpha-[H5W18O59(IO3)](6-), containing I(V)O3(-) within a
      {W18O54} metal oxide framework has been prepared and shown by X-ray
      crystallography and mass spectrometry to be derived from the fully oxidised
      [H3W18O56(IO6)](6-) by two-electron reduction accompanied by a redox-triggered
      structural rearrangement where three I-O covalent bonds are broken. 

PMID- 24022580
TI  - Results and complications after laparoscopic sleeve gastrectomy.
AB  - PURPOSE: Laparoscopic sleeve gastrectomy (SG) has gained popularity and
      acceptance among bariatric surgeons, mainly due its low morbidity and mortality.
      The purpose of the present study was to evaluate the efficacy of SG on weight
      loss, and to determine the postoperative course, clinical presentation and
      treatment of complications after SG. METHODS: Between January 2006 and October
      2012, 153 consecutive patients underwent SG. All data were prospectively
      collected in a computerized database. RESULTS: This series comprised 119 females
      and 34 males with a median age of 46 years and a median preoperative BMI of 42.3
      kg/m2. The median EWL was 53.0 % after 18.4 months of follow-up. The median
      postoperative BMI was 33.3 kg/m2 (range 19.7-56.1 kg/m2). Eight patients (5.2 %)
      required re-laparoscopy to manage postoperative hemorrhage (3.3 %) and leakage
      (1.9 %). Neither abdominal drains nor postoperative contrast-swallow studies were
      successful in diagnosing hemorrhage or leaks in our patients. CONCLUSION: SG is
      an effective procedure to achieve significant short-term weight loss. Clinical
      signs, such as tachycardia, pain, fever and hypotension, provide the best
      evidence of the presence of postoperative leakage or bleeding. An early diagnosis
      of these complications is the key to ensuring adequate treatment with immediate
      re-laparoscopy.

PMID- 24022581
TI  - Pericardial synovial sarcoma: a case report and review of the literature.
AB  - Primary pericardial synovial sarcoma is a rare disease. We herein report a case
      of synovial sarcoma that originated in the epicardium. A 13-year-old male visited
      our hospital with a fever and chest pain. Copious pericardial effusion and a
      large intrapericardial tumor were detected. An open-chest tumor resection was
      performed. A solid nodular tumor was observed in the pericardial cavity. The
      tumor was a polypoid mass that was pedunculated and grew from the inner surface
      of the pericardium near the origin of the SVC and ascending aorta.
      Histologically, the tumor cells were uniformly spindle shaped, with an ovoid or
      oval nucleus, and formed solid, compact sheets and fascicles. A storiform pattern
      was also observed. Based on the histopathological and immunohistochemical
      findings, and the fluorescence in situ hybridization detection of rearrangement
      of the SYT gene, a monophasic synovial sarcoma was diagnosed. We discuss the
      diagnosis and treatment of this case and review the pertinent literature. 

PMID- 24022582
TI  - Observation of detection-dependent multi-photon coherence times.
AB  - The coherence time constitutes one of the most critical parameters that
      determines whether or not interference is observed in an experiment. For photons,
      it is traditionally determined by the effective spectral bandwidth of the photon.
      Here we report on multi-photon interference experiments in which the multi-photon
      coherence time, defined by the width of the interference signal, depends on the
      number of interfering photons and on the measurement scheme chosen to detect the
      particles. A theoretical analysis reveals that all multi-photon interferences
      with more than two particles feature this dependence, which can be attributed to
      higher-order effects in the mutual indistinguishability of the particles. As a
      striking consequence, a single, well-defined many-particle quantum state can
      exhibit qualitatively different degrees of interference, depending on the chosen
      observable. Therefore, optimal sensitivity in many-particle quantum
      interferometry can only be achieved by choosing a suitable detection scheme. 

PMID- 24022583
TI  - Diffusion tensor imaging and tractography of the kidney in children: feasibility
      and preliminary experience.
AB  - BACKGROUND: Functional magnetic resonance urography (fMRU) provides morphological
      and functional information based on perfusion. Diffusion tensor imaging (DTI)
      complements fMRU by measuring renal microstructure and provides insight into the
      relationship between renal structure and function. OBJECTIVE: To evaluate the
      feasibility and utility of renal DTI and tractography in the setting of fMRU in
      children. MATERIALS AND METHODS: We prospectively enrolled 9 children (6 boys, 3
      girls) with a mean age of 4.3 years (range 6 months to 14.8 years). All children
      were examined with MRI at 3.0 tesla. DTI was acquired with an echo-planar
      sequence (TR/TE = 2,300/69 ms, b = 300 s/mm2) with 12 non-collinear directions
      and 3 signal averages. Functional MRU results were used to group the moieties as
      normal or abnormal. Regions of interest were placed in the medulla and cortex to
      measure DTI parameters of microstructure. DTI tractography measures of
      parenchymal volume were compared to fMRU-derived volumes. RESULTS: We analyzed 19
      moieties (13 normal; 6 abnormal). Tractography of normal moieties showed numerous
      tracks with a radial arrangement and convergence into pyramids. Abnormal moieties
      did not show the radial arrangement or converging architecture and had tracks
      that were loosely arranged and left hollow spaces. Tractography volume correlated
      with MRU parenchymal volume (r 2 = 0.93, P < 0.005) and abnormal moieties
      exhibited greater tractography volume than normal moieties (P < 0.005).
      Tractography volume also correlated with age of the child (P < 0.001). In normal
      moieties, the medulla had higher fractional anisotropy (0.401 +/-0.05) than the
      cortex (0.183 +/- 0.03) (P < 0.001); fractional anisotropy in these regions did
      not change with age (P > 0.1). There were no differences in apparent diffusion
      coefficient values between the cortex and medulla (P > 0.5). We observed a trend
      of increasing apparent diffusion coefficient values with age in the cortex and
      medulla, which did not reach statistical significance (cortex: r2 = 0.21, P >
      0.1; medulla: r2 = 0.135, P > 0.1). CONCLUSION: DTI with tractography is feasible
      in children and can complement the functional information obtained from fMRU.

PMID- 24022585
TI  - Arxula adeninivorans recombinant urate oxidase and its application in the
      production of food with low uric acid content.
AB  - Hyperuricemia and its symptoms are becoming increasingly common worldwide.
      Elevated serum uric acid levels are caused by increased uric acid synthesis from
      food constituents and reduced renal excretion. Treatment in most cases involves
      reducing alcohol intake and consumption of meat and fish or treatment with
      pharmaceuticals. Another approach could be to reduce uric acid level in food,
      either during production or consumption. This work reports the production of
      recombinant urate oxidase by Arxula adeninivorans and its application to reduce
      uric acid in a food product. The A. adeninivorans urate oxidase amino acid
      sequence was found to be similar to urate oxidases from other fungi (61-65%
      identity). In media supplemented with adenine, hypoxanthine or uric acid,
      induction of the urate oxidase (AUOX) gene and intracellular accumulation of
      urate oxidase (Auoxp) was observed. The enzyme characteristics were analyzed from
      isolates of the wild-type strain A. adeninivorans LS3, as well as from those of
      transgenic strains expressing the AUOX gene under control of the strong
      constitutive TEF1 promoter or the inducible AYNI1 promoter. The enzyme showed
      high substrate specificity for uric acid, a broad temperature and pH range, high
      thermostability and the ability to reduce uric acid content in food.

PMID- 24022584
TI  - Recommendations for screening and detection of connective tissue disease
      associated pulmonary arterial hypertension.
AB  - OBJECTIVE: Pulmonary arterial hypertension (PAH) affects up to 15% of patients
      with connective tissue diseases (CTDs). Previous recommendations developed as
      part of larger efforts in PAH did not include detailed recommendations for
      patients with CTD-associated PAH. Therefore, we sought to develop recommendations
      for screening and early detection of CTD-associated PAH. METHODS: We performed a
      systematic review of the literature on the screening and diagnosis of PAH in CTD.
      Using the RAND/University of California, Los Angeles consensus methodology, we
      developed case scenarios followed by 2 stages of voting. First, international
      experts from a variety of specialties voted anonymously on the appropriateness of
      each case scenario. The experts then met face-to-face to discuss and resolve
      discrepant votes to arrive at consensus recommendations. RESULTS: The key
      recommendation stated that all patients with systemic sclerosis (SSc) should be
      screened for PAH. In addition, patients with mixed connective tissue disease or
      other CTDs with scleroderma features (scleroderma spectrum disorders) should be
      screened for PAH. It was recommended that screening pulmonary function tests
      (PFTs) with single-breath diffusing capacity for carbon monoxide, transthoracic
      echocardiogram, and measurement of N-terminal pro-brain natriuretic peptide (NT
      proBNP) be performed in all patients with SSc and scleroderma spectrum disorders.
      In patients with SSc and scleroderma spectrum disorders, transthoracic
      echocardiogram and PFTs should be performed annually. The full screening panel
      (transthoracic echocardiogram, PFTs, and measurement of NT-proBNP) should be
      performed as soon as any new signs or symptoms are present. CONCLUSION: We
      provide consensus-based, evidence-driven recommendations for screening and early
      detection of CTD-associated PAH. It is our hope that these recommendations will
      lead to earlier detection of CTD-associated PAH and ultimately improve patient
      outcomes.

PMID- 24022588
TI  - The evolution of research on ageing and nutrition.

PMID- 24022586
TI  - Silk gland factor-2, involved in fibroin gene transcription, consists of LIM
      homeodomain, LIM-interacting, and single-stranded DNA-binding proteins.
AB  - SGF-2 binds to promoter elements governing posterior silk gland-specific
      expression of the fibroin gene in Bombyx mori. We purified SGF-2 and showed that
      SGF-2 contains at least four gene products: the silkworm orthologues of LIM
      homeodomain protein Awh, LIM domain-binding protein (Ldb), a sequence-specific
      single-stranded DNA-binding protein (Lcaf), and the silk protein
      P25/fibrohexamerin (fhx). Using co-expression of these factors in Sf9 cells, Awh,
      Ldb, and Lcaf proteins were co-purified as a ternary complex that bound to the
      enhancer sequence in vitro. Lcaf interacts with Ldb as well as Awh through the
      conserved regions to mediate transcriptional activation in yeast. Misexpression
      of Awh in transgenic silkworms induces ectopic expression of the fibroin gene in
      the middle silk glands, where Ldb and Lcaf are expressed. Taken together, this
      study demonstrates that SGF-2 is a multisubunit activator complex containing Awh.
      Moreover, our results suggest that the Ldb.Lcaf protein complex serves as a
      scaffold to facilitate communication between transcriptional control elements. 

PMID- 24022589
TI  - Interaction of fatty acid genotype and diet on changes in colonic fatty acids in
      a Mediterranean diet intervention study.
AB  - A Mediterranean diet increases intakes of n-3 and n-9 fatty acids and lowers
      intake of n-6 fatty acids. This can impact colon cancer risk as n-6 fatty acids
      are metabolized to proinflammatory eicosanoids. The purpose of this study was to
      evaluate interactions of polymorphisms in the fatty acid desaturase (FADS) genes,
      FADS1 and FADS2, and changes in diet on fatty acid concentrations in serum and
      colon. A total of 108 individuals at increased risk of colon cancer were
      randomized to either a Mediterranean or a Healthy Eating diet. Fatty acids were
      measured in both serum and colonic mucosa at baseline and after six months. Each
      individual was genotyped for four single-nucleotide polymorphisms in the FADS
      gene cluster. Linear regression was used to evaluate the effects of diet,
      genotype, and the diet by genotype interaction on fatty acid concentrations in
      serum and colon. Genetic variation in the FADS genes was strongly associated with
      baseline serum arachidonic acid (n-6) but serum eicosapentaenoic acid (n-3) and
      colonic fatty acid concentrations were not significantly associated with
      genotype. After intervention, there was a significant diet by genotype
      interaction for arachidonic acid concentrations in colon. Subjects who had all
      major alleles for FADS1/2 and were following a Mediterranean diet had 16% lower
      arachidonic acid concentrations in the colon after six months of intervention
      than subjects following the Healthy Eating diet. These results indicate that FADS
      genotype could modify the effects of changes in dietary fat intakes on
      arachidonic acid concentrations in the colon.

PMID- 24022590
TI  - The parity-associated microenvironmental niche in the omental fat band is
      refractory to ovarian cancer metastasis.
AB  - Ovarian cancer is an insidious and aggressive disease of older women, typically
      undiscovered before peritoneal metastasis due to its asymptomatic nature and lack
      of early detection tools. Epidemiologic studies suggest that child-bearing
      (parity) is associated with decreased ovarian cancer risk, although the molecular
      mechanisms responsible for this phenomenon have not been delineated. Ovarian
      cancer preferentially metastasizes to the omental fat band (OFB), a secondary
      lymphoid organ that aids in filtration of the peritoneal serous fluid (PSF) and
      helps combat peritoneal infections. In the present study, we assessed how parity
      and age impact the immune compositional profile in the OFB of mice, both in the
      homeostatic state and as a consequence of peritoneal implantation of ovarian
      cancer. Using fluorescence-activated cell sorting analysis and quantitative real
      time PCR, we found that parity was associated with a significant reduction in
      omental monocytic subsets and B1-B lymphocytes, correlating with reduced
      homeostatic expression levels of key chemoattractants and polarization factors
      (Ccl1, Ccl2, Arg1, and Cxcl13). Of note, parous animals exhibited significantly
      reduced tumor burden following intraperitoneal implantation compared with
      nulliparous animals. This was associated with a reduction in tumor-associated
      neutrophils and macrophages, as well as in the expression levels of their
      chemoattractants (Cxcl1 and Cxcl5) in the OFB and PSF. These findings define a
      preexisting "parity-associated microenvironmental niche" in the OFB that is
      refractory to metastatic tumor seeding and outgrowth. Future studies designed to
      manipulate this niche may provide a novel means to mitigate peritoneal
      dissemination of ovarian cancer.

PMID- 24022591
TI  - Fluid intelligence and empathy in association with personality  disorder trait
      scores: exploring the link.
AB  - There is some evidence that fluid intelligence as well as empathy may be
      significantly related to personality disorders (PDs). To our knowledge, no study
      has addressed those issues simultaneously in all 10 DSM PDs in a sample of the
      general population. We analysed data from 196 participants aged 20-41 from the
      Epidemiology Survey of the Zurich Programme for Sustainable Development of Mental
      Health Services (ZInEP), a comprehensive psychiatric survey in the general
      population of Zurich, Switzerland. We assessed the digit symbol-coding test
      (DSCT), the "reading the mind in the eyes" test (RMET) and the interpersonal
      reactivity index (IRI). Both measures of cognitive empathy (i.e. RMET and IRI
      perspective taking) were not related to any PD trait-score. The total PD trait
      score was significantly associated with low scores on DSCT and IRI empathic
      concern and high scores on IRI personal distress, which indicates a dose-response
      relationship in those measures. DSCT was particularly related to borderline PD,
      IRI empathic concern to schizoid and narcissistic PDs, and IRI personal distress
      to avoidant PD. The proportion of variance explained in the total PD trait-score
      accounted for by DSCT, IRI empathic concern and IRI personal distress was 2.6,
      2.3 and 13.3 %, respectively. Symptomatology and severity of PDs are related to
      low fluid intelligence and reduced emotional empathy as characterized by low
      empathic concern and high personal distress towards emotional expressions of
      others. Further research is needed that examines the association between
      cognitive empathy and personality pathology as well as potential clinical
      applications.

PMID- 24022592
TI  - Relational memory and hippocampal function in psychotic bipolar disorder.
AB  - Recent cognitive, genetic, and histological studies have highlighted significant
      overlap between psychotic bipolar disorder and schizophrenia. Specifically, both
      bipolar disorder and schizophrenia are characterized by interneuron dysfunction
      within the hippocampus, an essential structure for relational memory. Relational
      memory impairments are a common feature of schizophrenia, but have yet to be
      investigated in psychotic bipolar disorder. Here, we tested the hypothesis that
      psychotic bipolar disorder is characterized by relational memory deficits. We
      used a transitive inference (TI) paradigm, previously employed to quantify
      relational memory deficits in schizophrenia, to assess relational memory
      performance in 17 patients with psychotic bipolar disorder and 22 demographically
      matched control participants. Functional magnetic resonance imaging was used to
      examine hippocampal activity during recognition memory in patients and controls.
      Hippocampal volumes were assessed by manual segmentation. In contrast to our
      hypothesis, we found similar TI performance, hippocampal volume, and hippocampal
      recruitment during recognition memory in both groups. Both psychotic bipolar
      disorder patients and controls exhibited a positive correlation between
      hippocampal volume and relational memory performance. These data indicate that
      relational memory impairments are not a shared feature of non-affective and
      affective psychosis.

PMID- 24022594
TI  - An amphiphilic-like fluoroalkyl modified SiO2 nanoparticle@Nafion proton exchange
      membrane with excellent fuel cell performance.
AB  - A new route to enhance the cell performance of a Nafion proton exchange membrane
      is provided by incorporating fluoroalkyl modified SiO2 nanoparticles. In favor of
      the achieved amphiphilic-like surface characteristics of SiO2 nanoparticles, the
      so-formed nanocomposite membrane exhibited great enhancement of single cell
      performance at 80  degrees C: ~34% increase in output power relative to the
      Nafion reference and a superior maximum output power as high as 579.6 mW cm(-2).

PMID- 24022593
TI  - Ligand- and cell-dependent determinants of internalization and cAMP modulation by
      delta opioid receptor (DOR) agonists.
AB  - Signaling bias refers to G protein-coupled receptor ligand ability to
      preferentially activate one type of signal over another. Bias to evoke signaling
      as opposed to sequestration has been proposed as a predictor of opioid ligand
      potential for generating tolerance. Here we measured whether delta opioid
      receptor agonists preferentially inhibited cyclase activity over internalization
      in HEK cells. Efficacy (tau) and affinity (KA) values were estimated from
      functional data and bias was calculated from efficiency coefficients (log
      tau/KA). This approach better represented the data as compared to alternative
      methods that estimate bias exclusively from tau values. Log (tau/KA) coefficients
      indicated that SNC-80 and UFP-512 promoted cyclase inhibition more efficiently
      than DOR internalization as compared to DPDPE (bias factor for SNC-80: 50 and for
      UFP-512: 132). Molecular determinants of internalization were different in HEK293
      cells and neurons with betaarrs contributing to internalization in both cell
      types, while PKC and GRK2 activities were only involved in neurons. Rank orders
      of ligand ability to engage different internalization mechanisms in neurons were
      compared to rank order of E max values for cyclase assays in HEK cells.
      Comparison revealed a significant reversal in rank order for cyclase E max values
      and betaarr-dependent internalization in neurons, indicating that these responses
      were ligand-specific. Despite this evidence, and because kinases involved in
      internalization were not the same across cellular backgrounds, it is not possible
      to assert if the magnitude and nature of bias revealed by rank orders of maximal
      responses is the same as the one measured in HEK cells.

PMID- 24022595
TI  - Preoperative assessment and premedication in paediatrics.
AB  - Preoperative assessment and premedication represent important preparatory steps
      to ensuring a smooth and effective induction of anaesthesia. A thorough review of
      the child's medical history, previous anaesthetics, medications, allergies and
      family history is essential to design the optimal anaesthetic for the child and
      his/her surgery. Risks must be addressed with the parents as appropriate based on
      the local standards. Preoperative anxiolysis may assume several strategies, with
      premedication with a pharmacologic agent very common and most successful. This
      review focuses on the preoperative assessment and premedication for children
      undergoing elective surgery. 

PMID- 24022596
TI  - The Revised Cardiac Risk Index performs poorly in patients undergoing major
      vascular surgery: a prospective observational study.

PMID- 24022597
TI  - The chronicity of tonsillitis is significantly correlated with an increase in an
      LTi cell portion.
AB  - The current study explored the relationship between lymphoid tissue inducer (LTi)
      cells and patients' clinical and immunological status. LTi cells are critical for
      lymphoid tissue development and maintenance of CD4 T cell-dependent immune
      responses. The percentage of CD117+CD3-CD56-CD127+ RORgamma+ LTi cells isolated
      from human tonsils was determined and correlated with changes in other immune
      subsets and clinical factors. We found that the portion of LTi and CD4 T cells
      was significantly increased in chronic tonsillitis compared to non-inflamed
      tonsils. Additionally, the expression of OX40 by memory CD4 T cells and OX40
      ligand (OX40L) and interleukin (IL)-22 by LTi cells was higher in chronically
      inflamed tonsils. The treatment for tonsillitis with ibuprofen did not alter LTi
      cell viability and the expression of OX40L and IL-22. These results demonstrate
      that during chronic inflammation, LTi cells are increased and express higher
      levels of OX40L and IL-22, and this is correlated with an increase in memory CD4
      T cells.

PMID- 24022598
TI  - The protective effect of fenofibrate against TNF-alpha-induced CD40 expression
      through SIRT1-mediated deacetylation of NF-kappaB in endothelial cells.
AB  - Fenofibrate, as a lipid-lowering drug in clinic, participates in the regulation
      of inflammatory response. Recently, increasing studies have indicated that
      sirtuin1 (SIRT1), a NAD+-dependent deacetylase, has potential anti-inflammatory
      effect in endothelial cells. However, whether the regulatory effect of
      fenofibrate on inflammation response is mediated by SIRT1 remains unclear. The
      aim of this study was to investigate the effect of fenofibrate on the expressions
      of SIRT1 and pro-inflammatory cytokine CD40 in endothelial cells and explore the
      underlying mechanisms. The results showed that fenofibrate upregulated SIRT1
      expression and inhibited CD40 expression in TNF-alpha-stimulated endothelial
      cells, but these effects were reversed by peroxisome proliferator-activated
      receptor-alpha (PPARalpha) antagonist GW6471. Furthermore, SIRT1 inhibitors
      sirtinol/nicotinamide (NAM) or SIRT1 knockdown could attenuate the effect of
      fenofibrate on CD40 expression in endothelial cells. Importantly, NF-kappaB
      inhibitor pyrrolidine dithiocarbamate (PDTC) augmented the effect of fenofibrate
      on CD40 expression. Further study found that fenofibrate decreased the expression
      of acetylated-NF-kappaB p65 (Ac-NF-kappaB p65) in TNF-alpha-stimulated
      endothelial cells, which was abolished by SIRT1 knockdown. These results indicate
      that fenofibrate has protective effect against TNF-alpha-induced CD40 expression
      through SIRT1-mediated deacetylation of the p65 subunit of NF-kappaB.

PMID- 24022600
TI  - How I do it: side to side posterior inferior cerebellar artery - posterior
      inferior cerebellar artery bypass procedure.
AB  - BACKGROUND: An intracranial in situ side to side posterior circulation procedure
      is performed infrequently. The scope of treatment modalities of vertebral artery
      PICA aneurysms and vertebral dissections is limited due to the lack of many
      representations of this procedure's technical nuances. METHODS: To demonstrate
      the technical nuances of a PICA-PICA side to side bypass in a 50-year-old woman
      with a dissecting vertebral-PICA junction pseudoaneurysm. CONCLUSION: Details of
      the pre-operative evaluation, decision process and operative nuances of side to
      side PICA-PICA bypass are described. Indications and limitations are emphasized.
      Vascular neurosurgeons should consider this elegant procedure in their treatment
      armamentarium.

PMID- 24022601
TI  - Obtaining specimens with slowed, accelerated and reversed aging in the honey bee
      model.
AB  - Societies of highly social animals feature vast lifespan differences between
      closely related individuals. Among social insects, the honey bee is the best
      established model to study how plasticity in lifespan and aging is explained by
      social factors. The worker caste of honey bees includes nurse bees, which tend
      the brood, and forager bees, which collect nectar and pollen. Previous work has
      shown that brain functions and flight performance senesce more rapidly in
      foragers than in nurses. However, brain functions can recover, when foragers
      revert back to nursing tasks. Such patterns of accelerated and reversed
      functional senescence are linked to changed metabolic resource levels, to
      alterations in protein abundance and to immune function. Vitellogenin, a yolk
      protein with adapted functions in hormonal control and cellular defense, may
      serve as a major regulatory element in a network that controls the different
      aging dynamics in workers. Here we describe how the emergence of nurses and
      foragers can be monitored, and manipulated, including the reversal from typically
      short-lived foragers into longer-lived nurses. Our representative results show
      how individuals with similar chronological age differentiate into foragers and
      nurse bees under experimental conditions. We exemplify how behavioral reversal
      from foragers back to nurses can be validated. Last, we show how different
      cellular senescence can be assessed by measuring the accumulation of lipofuscin,
      a universal biomarker of senescence. For studying mechanisms that may link social
      influences and aging plasticity, this protocol provides a standardized tool set
      to acquire relevant sample material, and to improve data comparability among
      future studies. 

PMID- 24022602
TI  - Effect of acetylsalicylic acid on microvascular thrombosis in autologous breast
      reconstruction.
AB  - Although advances in microsurgery have increased success rates of autologous
      breast reconstruction, microvascular thrombosis still remains a major concern as
      a cause of flap failure. At present, no evidence-based guidelines on
      pharmacological prevention of microvascular thrombosis exist. This study
      investigates the effect of acetylsalicylic acid on the incidence of microvascular
      complications in patients undergoing autologous breast reconstruction. Patients
      undergoing deep inferior epigastric artery perforator or free transverse rectus
      abdominis myocutaneous flap breast reconstruction at two academic centers in the
      Netherlands between 2005 and 2011 were included. Patients at one center received
      once daily 0.6 mL of nadroparine and 40 mg acetylsalicylic acid, while patients
      at the other center received 0.6 mL nadroparine only. A total of 430 consecutive
      patients underwent 592 breast reconstructions. No statistically significant
      differences were found between the two groups in the incidence of flap failure
      (2.8 and 2.5%), microvascular thromboembolic complications (2.6 and 3.8%), venous
      congestion (3.4 and 2.8%), or overall complications (28.0 and 32.3%). Hematoma
      tended to occur more often in the group receiving acetylsalicylic acid (9.2 and
      4.7%).It was found that no protective effect of acetylsalicylic acid on
      microvascular complications was present. Given its known risks and the somewhat
      increased occurrence of hematoma in the present study, we stopped to routinely
      administer acetylsalicylic acid after autologous breast reconstruction.

PMID- 24022599
TI  - Involvement of Gr-1 dull+ cells in the production of TNF-alpha and IL-17 and
      exacerbated systemic inflammatory response caused by lipopolysaccharide.
AB  - Systemic inflammatory response syndrome (SIRS) is a life-threatening disease.
      Recent reports have demonstrated that the immunoregulatory cells that express Gr
      1, a granulocyte surface antigen, play a critical role in various pathological
      conditions. In the present study, we have established a mouse model of SIRS and
      addressed the possible contribution of Gr-1+ cells in this model. C57BL/6 mice
      were injected intraperitoneally with anti-Gr-1 mAb or control IgG 1 day before
      administration of lipopolysaccharide (LPS). All of the mice that received anti-Gr
      1 mAb and LPS died early as a result of hypothermia and severe emaciation,
      whereas mice treated with control IgG and LPS survived the observation period. In
      mice treated with anti-Gr-1 mAb and LPS, acute inflammatory changes with alveolar
      hemorrhage were observed in the lung and proximal convoluted tubule necrosis was
      observed in the kidney. Serum TNF-alpha and IL-17A levels were markedly increased
      in anti-Gr-1 mAb-pretreated mice compared with those in control IgG-treated mice
      at 1 and 3 h after LPS administration, respectively. Flow cytometric analysis
      revealed an increase in TNF-alpha and IL-17A expression in Gr-1 dull+ cells in
      the peripheral blood mononuclear cells. Neutralization of TNF-alpha by a specific
      mAb almost completely reversed the clinical course and inhibited the increased
      production of IL-17A. In addition, IL-17A KO mice were less susceptible to the
      lethality in this model. Thus, we established a mouse model of severe SIRS and
      suggested that Gr-1 dull+ cells may play a critical role in the development of
      this pathological condition.

PMID- 24022603
TI  - Maxillary reconstruction using chimeric flaps of the subscapular artery system
      without vein grafts and the novel usage of chimeric flaps.
AB  - The purpose of this study was to overcome the disadvantages associated with the
      shortness of the vascular pedicle of subscapular system combined flaps when
      performing the maxillary reconstruction procedure. Combined flaps of the
      subscapular artery system were used for maxillary reconstruction. A latissimus
      dorsi myocutaneous flap, a scapular fasciocutaneous flap, and two kinds of
      scapular bone flaps were elevated as combined flaps. Next, the circumflex
      scapular artery (CS) and vein were cut off from the combined flaps and
      anastomosed to the serratus anterior branch, thereby establishing chimeric flaps.
      Then, maxillary reconstruction was performed using these flaps. We encountered
      two patients who underwent maxillectomy for maxillary cancer. Satisfactory
      improvements in facial shape were obtained in both cases. In cases in which
      combined flaps of the subscapular artery system are used for maxillary
      reconstruction, the biggest problem is that the vascular pedicle does not reach
      the recipient vessel in the neck due to the shortness of the CS. Therefore, vein
      grafts are generally performed to extend the flaps to the maxilla. Our novel
      procedure has the great advantages of long vascular pedicles and high flexibility
      in setting the flaps without the use of vein grafts. 

PMID- 24022604
TI  - Anton Pavlovic Cechov's journey to the penitentiary island of Sakhalin in 1890:
      an early and personal interpretation and practical application of Red Cross
      ideas.

PMID- 24022605
TI  - Structural characterization of thioether-bridged bacteriocins.
AB  - Bacteriocins are a group of ribosomally synthesized antimicrobial peptides
      produced by bacteria, some of which are extensively post-translationally
      modified. Some bacteriocins, namely the lantibiotics and sactibiotics, contain
      one or more thioether bridges. However, these modifications complicate the
      structural elucidation of these bacteriocins using conventional techniques. This
      review will discuss the techniques and strategies that have been applied to
      determine the primary structures of lantibiotics and sactibiotics. A major
      challenge is to identify the topology of thioether bridges in these peptides
      (i.e., which amino-acid residues are involved in which bridges). Edman
      degradation, NMR spectroscopy and tandem MS have all been commonly applied to
      characterize these bacteriocins, but can be incompatible with the post
      translational modifications present. Chemical modifications to the modified
      residues, such as desulfurization and reduction, make the treated bacteriocins
      more compatible to analysis by these standard peptide analytical techniques.
      Despite their differences in structure, similar strategies have proved useful to
      study the structures of both lantibiotics and sactibiotics. 

PMID- 24022606
TI  - C-glycosylation of anhydrotetracycline scaffold with SsfS6 from the SF2575
      biosynthetic pathway.
AB  - Glycosylation with deoxysugar is a common strategy used by nature to introduce
      structural diversity and biological activities among natural products. In this
      study, we biochemically confirmed the activities of SsfS6, a C
      glycosyltransferase in the SF2575 biosynthetic pathway, as a regioselective D
      olivose transferase that acts on the C-9 position of an anhydrotetracycline
      aglycon. To perform the glycosyl transfer reaction using Escherichia coli as a
      whole-cell biocatalyst, we reconstituted the biosynthesis of TDP-D-olivose using
      a heterologous pathway. Under in vivo conditions, SsfS6 transferred multiple
      endogenous sugar substrates, in addition to D-olivose, to the anhydrotetracycline
      substrate, demonstrating broad substrate tolerance and potential as a
      tetracycline-diversifying enzyme. 

PMID- 24022607
TI  - In vitro effectiveness of anidulafungin against Candida sp. biofilms.
AB  - This study furnishes deeper insights to previous works on anidulafungin,
      demonstrating the potent activity against Candida strains planktonic cells and
      biofilms. Candida sp., associated with many biomaterial-related infections, give
      rise to infective pathologies typically associated with biofilm formation. We
      recently determined the in vitro antifungal activities of echinocandin
      anidulafungin in association with some antifungal drugs against some Candida
      strains in their planktonic states. A total of 11 Candida strains biofilms were
      tested in this study: six Candida albicans, three C. parapsilosis and two C.
      tropicalis. All yeast isolates and ATCC strains were stored at -20 degrees C in
      glycerol stocks and were subcultured on antimicrobial agent-free Sabouraud
      dextrose agar plates. MIC endpoints were determined colorimetrically by using the
      indicator 2,3-bis(2-methoxy-4-nitro-5-sulphophenyl)-5-[(phenylamino)carbonyl]-2H
      tetrazolium hydroxide (XTT) with menadione as electron-coupling agent. The
      activity of anidulafungin was assessed using in vitro microbiological model
      relevant for clinical practice. Anidulafungin showed a strong activity in vitro
      against both planktonic and biofilms cells, and our study confirms that high
      anidulafungin concentrations might establish paradoxical growth effect in C.
      albicans and C. tropicalis biofilms.

PMID- 24022609
TI  - Water adsorption in hydrophilic zeolites: experiment and simulation.
AB  - We have measured experimental adsorption isotherms of water in zeolite LTA4A, and
      studied the regeneration process by performing subsequent adsorption cycles after
      degassing at different temperatures. We observed incomplete desorption at low
      temperatures, and cation rearrangement at successive adsorption cycles. We also
      developed a new molecular simulation force field able to reproduce experimental
      adsorption isotherms in the range of temperatures between 273 K and 374 K. Small
      deviations observed at high pressures are attributed to the change in the water
      dipole moment at high loadings. The force field correctly describes the
      preferential adsorption sites of water at different pressures. We tested the
      influence of the zeolite structure, framework flexibility, and cation mobility
      when considering adsorption and diffusion of water. Finally, we performed checks
      on force field transferability between different hydrophilic zeolite types,
      concluding that classical, non-polarizable water force fields are not
      transferable. 

PMID- 24022608
TI  - Eating Disorders and Disordered Eating in Type 1 Diabetes: Prevalence, Screening,
      and Treatment Options.
AB  - This review is focused on the prevalence of eating disorders and disordered
      eating behaviors in individuals with type 1 diabetes. Recent research indicates
      higher prevalence rates of eating disorders among people with type 1 diabetes
      compared with their peers without diabetes. Eating disorders and disordered
      eating behaviors-especially insulin omission-are associated with poorer glycemic
      control and serious risk for increased morbidity and mortality. Screening should
      begin in pre-adolescence and continue through early adulthood, as many disordered
      eating behaviors begin during the transition to adolescence and may persist for
      years. Available screening tools and treatment options are reviewed. Given the
      complexity of diabetes management in combination with eating disorder treatment,
      it is imperative to screen early and often, in order to identify those most
      vulnerable and begin appropriate treatment in a timely manner.

PMID- 24022610
TI  - Investigating the physiological response of Pichia (Komagataella) pastoris GS115
      to the heterologous expression of misfolded proteins using chemostat cultures.
AB  - Pichia pastoris is widely used as a host system for heterologous protein
      expression in both academia and industry. Production is typically accomplished by
      a fed-batch induction process that is known to have negative impacts on cell
      physiology that impose limits on both protein yields and quality. We have
      analysed recombinant protein production in chemostat cultures to understand the
      physiological responses associated with methanol-induced production of two human
      lysozyme variants with different degrees of misfolding by P. pastoris.
      Confounding variables associated with nutrient stress or growth-rate are
      minimised during steady-state growth in chemostats. Comparison of transcriptome
      level data obtained during the non-inducing and inducing steady states identified
      changes in expression of only about 1 % of the genome during production of either
      an amyloidogenic human lysozyme variant prone to intracellular aggregation (I56T)
      or a misfolded but secretable variant (T70N), indicating near-complete
      acclimation to their production. A marked, but temporary, stress response
      involving both the unfolded protein response (UPR) and ER-associated degradation
      pathway was observed during the transient between steady states, particularly
      following induction of the T70N variant synthesis, and was accompanied by changes
      in expression of around 50 antisense transcripts. The results suggest that
      optimal heterologous protein production could best be achieved by a continuous
      process that minimises the number of methanol-induced transients experienced by
      the cultures. The processing of HAC1 mRNA required for the UPR was found to be
      constitutive in the culture conditions used, even in the absence of recombinant
      protein induction.

PMID- 24022612
TI  - Scleroderma renal crisis.
AB  - Systemic sclerosis is an autoimmune connective tissue disorder characterized by
      endothelial cell injury, vascular hyper-reactivity, obliterative
      microvasculopathy and excess collagen deposition, particularly within the dermis
      of the skin. Table 1 outlines the various terms that are used to describe the
      extent and location of sclerosis. Limited cutaneous and diffuse cutaneous are the
      two main forms that exist. 

PMID- 24022611
TI  - Development of a chemically defined medium for the production of the antibiotic
      platensimycin by Streptomyces platensis.
AB  - The actinomycete Streptomyces platensis produces two compounds that display
      antibacterial activity: platensimycin and platencin. These compounds were
      discovered by the Merck Research Laboratories, and a complex insoluble production
      medium was reported. We have used this medium as our starting point in our
      studies. In a previous study, we developed a semi-defined production medium,
      i.e., PM5. In the present studies, by varying the concentration of the components
      of PM5, we were able to develop a superior semi-defined medium, i.e., PM6, which
      contains a higher concentration of lactose. Versions of PM6, containing lower
      concentrations of all components, were also found to be superior to PM5. The new
      semi-defined production media contain dextrin, lactose, MOPS buffer, and ammonium
      sulfate in different concentrations. We determined antibiotic production
      capabilities using agar diffusion assays and chemical assays via thin-layer
      silica chromatography and high-performance liquid chromatography. We reduced
      crude nutrient carryover from the seed medium by washing the cells with distilled
      water. Using these semi-defined media, we determined that addition of the semi
      defined component soluble starch stimulated antibiotic production and that it and
      dextrin could both be replaced with glucose, resulting in the chemically defined
      medium, PM7.

PMID- 24022613
TI  - Ultrafiltration: contemporary management of fluid overload.
AB  - Chronic heart failure is common, with an incidence of 1 in 1000 of the general
      population, and is rising at 10% per year (Cowie et al, 1999: Owan et al, 2006).
      In the UK, the prevalence is estimated at 900000 patients, with only 7000 of
      these under the age of 65 years (Petersen et al, 2002). Approximately 200000 are
      in New York Heart Association (NYHA) functional class III/IV, meaning they are
      breathless on mild exertion. 

PMID- 24022614
TI  - Splinter haemorrhages, Osler's nodes, Janeway lesions and Roth spots: the
      peripheral stigmata of endocarditis.
AB  - Infective endocarditis is a serious endo-vascular infection, potentially
      affecting not only native heart valves, but also intra-vascularly implanted
      foreign materials such as valvular prostheses and pacemaker electrodes (Westphal
      et al, 2009). 

PMID- 24022615
TI  - Attending coroner's court: a practical guide.
AB  - It will happen to many of us during our medical careers. We will receive a
      summons to give evidence at a coroner's inquest, and the nerves will start to run
      riot. 

PMID- 24022616
TI  - Reactions of an isolable dialkylsilylene with aromatic nitriles providing a new
      type of heterosilole.
AB  - The 1 : 2 reactions of isolable dialkylsilylene with nitriles having electron
      donating aromatic substituents gave 1,4-diaza-2-siloles with a hitherto-unknown
      type of ring system, in contrast to the previous studies showing exclusive
      formation of the corresponding 1,3-diaza-2-siloles; the reactions of with
      aromatic nitriles bearing electron-withdrawing substituents afforded the latter
      ring system. The remarkable diversity of the reactions is explained by invoking
      the corresponding nitrile silaylides as key intermediates whose polarity switches
      depending on the substituents of nitriles. 

PMID- 24022617
TI  - Brain stones revisited-between a rock and a hard place.
AB  - OBJECTIVES AND METHODS: Large intracranial calcifications are occasionally
      encountered in routine computed tomography (CT) scans of the brain. These
      calcifications, also known as "brain stones", can be classified according to
      location and aetiology. Combining imaging findings with relevant clinical history
      and physical examination can help narrow down the differential diagnosis and may
      allow confident diagnosis in certain situations. RESULTS: This article provides a
      pictorial review illustrating various clinical entities resulting in brain
      stones. DISCUSSION: Based on location, brain stones can be classified as extra-
      or intra-axial. Extra-axial brain stones comprise tumours and exaggerated
      physiological calcifications. Intra-axial brain stones can further be classified
      according to aetiology, namely neoplastic, vascular, infectious, congenital and
      endocrine/metabolic. Imaging findings combined with essential clinical
      information can help in narrowing the differential diagnosis, determining disease
      state and evaluating effect of therapy. TEACHING POINTS: * Based on location,
      brain stones can be either extra- or intra-axial. * Extra-axial brain stones
      comprise tumours and exaggerated physiological calcifications. * Intra-axial
      aetiologies include neoplastic, vascular, infectious, congenital and
      endocrine/metabolic. * CT scan is the mainstay in identifying and characterising
      brain stones. * Certain MRI sequences (gradient echo T2* and susceptibility
      weighted imaging) are considered adjunctive.

PMID- 24022618
TI  - A distinct human CD4+ T cell subset that secretes CXCL13 in rheumatoid synovium.
AB  - OBJECTIVE: A subset of CD4+ T cells in the synovium of patients with rheumatoid
      arthritis (RA) produce CXCL13, a chemokine that is crucial for the formation of
      germinal centers. This study was undertaken to determine the relevance of this
      population to known subsets of T helper cells and to proinflammatory cytokines,
      and how these cells are generated. METHODS: The expression of Th markers and
      CXCL13 by CD4+ T cells in RA synovium and the involvement of proinflammatory
      cytokines in CXCL13 production were assessed. We also investigated whether
      CXCL13+CD4+ T cells could be newly induced. RESULTS: CXCL13+CD4+ T cells in RA
      synovium were negative for interferon-gamma (IFNgamma), interleukin-4 (IL-4), IL
      17, FoxP3, and CXCR5 and expressed low levels of inducible T cell costimulator,
      indicating that this population is a distinct human CD4 subset. T cell receptor
      (TCR) stimulation of CD4+ T cells, obtained from RA synovium with low expression
      of CXCL13, promptly induced CXCL13 production and addition of proinflammatory
      cytokines supported the long-term production of CXCL13. These findings indicate
      that CXCL13-producing CD4+ T cells can be in a memory state ready to be
      reactivated upon TCR stimulation and that proinflammatory cytokines are involved
      in persistent CXCL13 production. TCR stimulation of CD4+ T cells from the blood
      of healthy volunteers, together with proinflammatory cytokine supplementation,
      induced a population that produced CXCL13, but not IFNgamma. Synovial T cells
      recruited CXCR5+ cells in a CXCL13-dependent manner. CONCLUSION: CXCL13-producing
      CD4+ T cells induced in RA synovium may play a role in the recruitment of CXCR5+
      cells, such as B cells and circulating follicular helper T cells, and in ectopic
      lymphoid neogenesis at sites of inflammation.

PMID- 24022619
TI  - Management of hyperphosphataemia in chronic kidney disease: summary of National
      Institute for Health and Clinical Excellence (NICE) guideline.
AB  - Bone disease and ectopic calcification are the two main consequences of
      hyperphosphataemia of chronic kidney disease (CKD). Observational studies have
      demonstrated that hyperphosphataemia in CKD is associated with increased
      mortality. Furthermore, the use of phosphate binders in dialysis patients is
      associated with significantly lower mortality. The UK Renal Registry data show
      significant underachievement of phosphate targets in dialysis patients. It is
      believed to be due to wide variation in how management interventions are used.
      The National Institute for Health and Clinical Excellence (NICE) has developed a
      guideline on the management of hyperphosphataemia in CKD. This is based on the
      evidence currently available using the Grading of Recommendations Assessment,
      Development and Evaluation (GRADE) methodology. This review outlines the
      recommendations including research recommendations and discusses methodology,
      rationale and challenges faced in developing this guideline and the health
      economic model used to assess the cost-effectiveness of different phosphate
      binders.

PMID- 24022620
TI  - Are "anti-aging medicine" and "successful aging" two sides of the same coin?
      Views of anti-aging practitioners.
AB  - OBJECTIVES: This article analyzes data from interviews with anti-aging
      practitioners to evaluate how their descriptions of the work they do, their
      definitions of aging, and their goals for their patients intersect with
      gerontological views of "successful aging." METHOD: Semistructured interviews
      were conducted with a sample of 31 anti-aging practitioners drawn from the
      directory of the American Academy for Anti-Aging Medicine. RESULTS: Qualitative
      analysis of the transcripts demonstrate that practitioners' descriptions of their
      goals, intentionally or unintentionally, mimic the dominant models of "successful
      aging." These include lowered risk of disease and disability, maintenance of high
      levels of mental and physical function, and continuing social engagement. Yet,
      the means and modes of achieving these goals differ markedly between the two
      groups, as do the messages that each group puts forth in defending their
      positions. DISCUSSION: Anti-aging practitioners' adoption of the rhetoric of
      successful aging reflects the success of successful aging models in shaping
      popular conceptions of what aging is and an ethos of management and control over
      the aging process. The overlap between anti-aging and successful aging rhetoric
      also highlights some of the most problematic social, cultural, and economic
      consequences of efforts made to reconceptualize old age.

PMID- 24022621
TI  - Multiple-capillary measurement of RBC speed, flux, and density with optical
      coherence tomography.
AB  - As capillaries exhibit heterogeneous and fluctuating dynamics even during
      baseline, a technique measuring red blood cell (RBC) speed and flux over many
      capillaries at the same time is needed. Here, we report that optical coherence
      tomography can capture individual RBC passage simultaneously over many
      capillaries located at different depths. Further, we demonstrate the ability to
      quantify RBC speed, flux, and linear density. This technique will provide a means
      to monitor microvascular flow dynamics over many capillaries at different depths
      at the same time. 

PMID- 24022622
TI  - IL-10 deficiency exacerbates the brain inflammatory response to permanent
      ischemia without preventing resolution of the lesion.
AB  - Stroke induces inflammation that can aggravate brain damage. This work examines
      whether interleukin-10 (IL-10) deficiency exacerbates inflammation and worsens
      the outcome of permanent middle cerebral artery occlusion (pMCAO). Expression of
      IL-10 and IL-10 receptor (IL-10R) increased after ischemia. From day 4, reactive
      astrocytes showed strong IL-10R immunoreactivity. Interleukin-10 knockout (IL-10
      KO) mice kept in conventional housing showed more mortality after pMCAO than the
      wild type (WT). This effect was associated with the presence of signs of colitis
      in the IL-10 KO mice, suggesting that ongoing systemic inflammation was a
      confounding factor. In a pathogen-free environment, IL-10 deficiency slightly
      increased infarct volume and neurologic deficits. Induction of proinflammatory
      molecules in the IL-10 KO brain was similar to that in the WT 6 hours after
      ischemia, but was higher at day 4, while differences decreased at day 7.
      Deficiency of IL-10 promoted the presence of more mature phagocytic cells in the
      ischemic tissue, and enhanced the expression of M2 markers and the T-cell
      inhibitory molecule CTLA-4. These findings agree with a role of IL-10 in
      attenuating local inflammatory reactions, but do not support an essential
      function of IL-10 in lesion resolution. Upregulation of alternative
      immunosuppressive molecules after brain ischemia can compensate, at least in
      part, the absence of IL-10. 

PMID- 24022623
TI  - Uncoupling PSD-95 interactions leads to rapid recovery of cortical function after
      focal stroke.
AB  - Since the most significant ischemic sequelae occur within hours of stroke, it is
      necessary to understand how neuronal function changes during this time. While
      histologic and behavioral models show the extent of stroke-related damage, only
      in vivo recordings can illustrate changes in brain activity during stroke and
      validate effectiveness of neuroprotective compounds. Spontaneous and evoked field
      potentials (fEPs) were recorded in the deep layers of the cortex with a linear
      microelectrode array for 3 hours after focal stroke in anesthetized rats. Tat
      NR2B9c peptide, which confers neuroprotection by uncoupling the PSD-95 protein
      from N-methyl-D-aspartate receptor (NMDAR), was administered 5 minutes before
      ischemia. Evoked field potentials were completely suppressed within 3 minutes of
      infarct in all ischemic groups. Evoked field potential recovery after stroke in
      rats treated with Tat-NR2B9c (83% of baseline) was greater compared with stroke
      only (61% of baseline) or control peptide (Tat-NR2B-AA; 67% of baseline) groups
      (P<0.001). Electroencephalography (EEG) power was higher in Tat-NR2B9c-treated
      animals at both 20 minutes and 1 hour (50% and 73% of baseline, respectively)
      compared with stroke-only and Tat-NR2B-AA-treated rats (P<0.05). Tat-NR2B9c
      significantly reduces stroke-related cortical dysfunction as evidenced by greater
      recovery of fEPs and EEG power; illustrating the immediate effects of the
      compound on poststroke brain function. 

PMID- 24022626
TI  - [Urticaria].

PMID- 24022624
TI  - Vascular aspects of cognitive impairment and dementia.
AB  - Hypertension and stroke are highly prevalent risk factors for cognitive
      impairment and dementia. Alzheimer's disease (AD) and vascular dementia (VaD) are
      the most common forms of dementia, and both conditions are preceded by a stage of
      cognitive impairment. Stroke is a major risk factor for the development of
      vascular cognitive impairment (VCI) and VaD; however, stroke may also predispose
      to AD. Hypertension is a major risk factor for stroke, thus linking hypertension
      to VCI and VaD, but hypertension is also an important risk factor for AD.
      Reducing these two major, but modifiable, risk factors-hypertension and stroke
      could be a successful strategy for reducing the public health burden of cognitive
      impairment and dementia. Intake of long-chain omega-3 polyunsaturated fatty acids
      (LC-n3-FA) and the manipulation of factors involved in the renin-angiotensin
      system (e.g. angiotensin II or angiotensin-converting enzyme) have been shown to
      reduce the risk of developing hypertension and stroke, thereby reducing dementia
      risk. This paper will review the research conducted on the relationship between
      hypertension, stroke, and dementia and also on the impact of LC-n3-FA or
      antihypertensive treatments on risk factors for VCI, VaD, and AD. 

PMID- 24022627
TI  - [Diagnosis and therapy of chronic urticaria-what is expected from the revision
      and update of the international guidelines? A report of the public consensus
      conference "URTICARIA 2012"].
AB  - In November 2012, the 4th International Consensus Meeting on Urticaria
      ("URTICARIA 2012") took place in Berlin with more than 300 participants. The
      international and the German guidelines for the definition, classification,
      diagnosis and management of urticaria are currently being developed based on this
      meeting. At the time of publication of this article, the guidelines are in the
      final process of international coordination. The previous international
      guidelines were updated based on prepared questions as well as a systematic
      review of the literature by an expert panel. The individual aspects were then
      discussed with all participants and decided upon, based on the Delphi method with
      general discussion and open poll. Here, at least a 75 % agreement was required.
      The new consensus modifies the previous international guidelines on
      classification and diagnosis and especially on therapy. The treatment algorithm
      has been changed to a three step approach. The first step is a second generation
      H1 antihistamine in standard dosage. The second step is increasing the dose up to
      4 times the standard dose. In the third step, additional treatment with
      omalizumab, cyclosporine A or montelukast is recommended as well as possibly
      systemic corticosteroids for a maximum of 7-10 days. H2 antihistamines and
      dapsone, which were included in the previous guideline as standard therapies, are
      no longer recommended for use by the updated and revised guidelines. 

PMID- 24022628
TI  - [Urticaria. Sometimes IgE-mediated?].
AB  - There are specific diagnostic recommendations for approaching chronic spontaneous
      urticaria, physical urticaria and special forms of urticaria. They include the
      detection of subclinical viral and bacterial infections, particularly with
      Helicobacter pylori. Frequently an autoimmune urticaria is diagnosed by using the
      autologous serum test. Less specific findings, such as leukocytosis and elevated
      CRP can sometimes be helpful in suggesting subclinical infections as the cause of
      acute urticaria; usually no further procedures are recommended. However, in cases
      with a long history of intermittent attacks, particularly with severe and
      generalized symptoms, it is recommended to look for IgE-mediated reactions (e.g.
      alpha-Gal, Omega-5-Gliadin). In our hands at the Department of Dermatology and
      Allergy at the Hannover Medical School a standardized set of diagnostic
      procedures was successfully established, and is now individually completed with
      selected single allergens and allergen components. 

PMID- 24022629
TI  - [Useful tools for documenting urticaria].
AB  - Urticaria is one of the most common inflammatory skin diseases. Many patients
      suffer for many years of the subtypes of urticaria. Because of their symptoms,
      urticaria patients have a very low quality of life and are subject to
      comorbidities. A structured approach with validated evaluation tools helps (1) to
      diagnose the respective subtype of the disease, (2) to define the disease
      activity and (3) to analyze the impact on quality of life. By virtue of this, it
      is possible to adequately diagnose and manage urticaria patients without major
      investment of time or manpower. Tools to measure disease intensity (urticaria
      activity score, angioedema activity score) and questionnaires for quality of life
      in the cases of chronic urticaria and angioedema have been developed. Suspected
      diagnoses of comorbidity such as depression or anxiety can be confirmed by the
      appropriate questionnaire (Hamilton Anxiety Depression Scale [HADS]). In addition
      diagnostic instruments are helpful to define the intensity of the disease,
      especially in cases of inducible urticaria. All these forms, scores and
      questionnaires are easy to learn and employ in daily practice. 

PMID- 24022630
TI  - [Confluent brown hyperkeratotic papules of the trunk and axillae].

PMID- 24022631
TI  - [Chronic spontaneous urticaria: An autoimmune disease?].
AB  - The identification of the causes of chronic spontaneous urticaria (CSU) is
      difficult. The recognition of functional autoantibodies against FcepsilonRI
      and/or against IgE in some patients with CSU led to the concept of autoimmune
      etiology of the disease. Clinical and laboratory features in a subpopulation of
      CSU patients also point to an autoimmune etiology of the disease. This review
      will present and discuss the relevance of functional autoantibodies in CSU
      pathogenesis and their implications for treatment and prognosis. 

PMID- 24022634
TI  - [Neonatal abstinence syndrome - change in therapy options?].

PMID- 24022635
TI  - [Follow-up studies about drug-therapy of epilepsies in childhood - a complex
      challenge].

PMID- 24022636
TI  - A patient nicknamed 'saline': atypical course with cystic fibrosis.

PMID- 24022632
TI  - [Phlebology in German departments of dermatology. An analysis on behalf of the
      German Society of Phlebology].
AB  - BACKGROUND: Phlebologic diseases have become extremely common and have major
      socio-economic impact. However, the percentage of dermatologists working in
      phlebology appears to be decreasing according to the data of the German Society
      of Phlebology (DGP). METHODS: To investigate the reasons for this development, we
      -on behalf of the DGP--sent a questionnaire to 120 German Departments of
      Dermatology in autumn 2012. RESULTS: In 76 returned questionnaires, the number of
      physicians with additional fellowship training in phlebology averaged 1.5; the
      average number of those who fulfill the criteria for training fellows in
      phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A
      special phlebologic outpatient clinic existed in 73.7 % of the departments.
      Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most
      frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy
      (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures
      (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and
      stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number
      of treatments was very heterogenous in the different departments. CONCLUSIONS:
      Phlebology definitely plays an important role in dermatology. Most departments
      fulfill the formal criteria for the license to conduct advanced training in
      phlebology. A wide spectrum of phlebological diagnostic and therapeutic
      procedures is available.

PMID- 24022638
TI  - A 3D microporous covalent organic framework with exceedingly high C3H8/CH4 and C2
      hydrocarbon/CH4 selectivity.
AB  - Here we present a new 3D microporous COF with a uniform pore size (0.64 nm). MCOF
      1 exhibits high adsorption selectivity towards C3H8, C2H6 and C2H4 over CH4 owing
      to the pore size and preferential adsorption. 

PMID- 24022639
TI  - Human papillomavirus: current status and issues of vaccination.
AB  - An association between human papillomavirus (HPV) infection and the development
      of cervical cancer was initially suggested over 30 years ago, and today there is
      clear evidence that certain subtypes of HPV are the causative agents of such
      malignancies. Papillomaviruses make up a vast family that comprises hundreds of
      different viruses. These viruses infect epithelia in humans and animals and cause
      benign hyperproliferative lesions, commonly called warts or papillomas, which can
      occasionally progress to squamous cell cancer. HPV infections are considered the
      most common among sexually transmitted diseases. One of the most prevalent cancer
      types induced by HPV (mostly types 16 and 18) is cervical cancer. Vaccination is
      the most effective means of preventing this infectious disease. These
      prophylactic vaccines, based on virus-like particles (VLPs), are extremely
      effective in providing protection from infection in almost 100 % of cases. VLP
      vaccines of HPV are subunit vaccines consisting only of the major viral capsid
      protein of HPV. There are two types of vaccine available: bivalent vaccine
      (against HPV-16/18) and quadrivalent vaccine (against HPV-6/11/16/18). Second
      generation prophylactic HPV vaccines, currently in clinical trials, may hold
      several merits over the current bivalent and quadrivalent vaccines, such as
      protection against additional oncogenic HPV types, less dependence on cold-chain
      storage and distribution, and non-invasive methods of delivery.

PMID- 24022637
TI  - Mitogenic signalling in the absence of epidermal growth factor receptor
      activation in a human glioblastoma cell line.
AB  - Epidermal growth factor receptor (EGFR) gene amplification and overexpression are
      commonly present in glioblastoma, and confer advantages of growth, invasiveness
      and radio/chemotherapy-resistance for tumour cells. Here, we assessed the role of
      EGFR activation for downstream mitogenic signalling in the commonly used
      glioblastoma cell line U251. Despite the high expression level, activation of
      EGFR under standard culture conditions was low. Intact EGFR function was verified
      by the rapid phosphorylation of EGFR and downstream mitogen-activated
      protein(MAP) kinase ERK1/2 upon addition of exogenous EGF to serum-starved cells.
      By contrast, addition of fetal bovine serum (FBS) activated downstream ERK1/2 via
      the MAP kinase kinase without phosphorylating EGFR. A phosphoreceptor tyrosine
      kinase array showed FBS-induced activation of insulin-like growth factor-1
      receptor (IGF-1R),and the IGF-1R inhibitor AG1024 inhibited FBS-induced
      phosphorylation of ERK1/2, implying IGF-1R as the major driver of FBS-associated
      mitogenic signalling in the absence of exogenous EGF. These findings have
      important implications for in vitro drug testing in glioblastoma. Moreover,
      activation of ERK1/2 was also strongly influenced by growth state and cell
      density of U251 cultures. Re-seeding exponentially growing cultures at high cell
      density induced p27/CDKN1B expression and suppressed P-ERK1/2 indicating a
      certain regulation of proliferation by contact inhibition. Strikingly, highly
      activated ERK1/2 signalling and cell cycle progression occurred when cells were
      released from plateau phase regardless of high seeding density. This phenomenon
      might implicate a proliferation response in the early recurrence observed after
      clinical therapy in glioblastoma patients. However, whether it will recapitulate
      in vivo remains to be demonstrated.

PMID- 24022640
TI  - Three proposed new bacteriophage genera of staphylococcal phages: "3alikevirus",
      "77likevirus" and "Phietalikevirus".
AB  - To date, most members of the Siphoviridae family of bacteriophages remain
      unclassified, including the 46 staphylococcal phages for which the complete
      genome sequences have been deposited in public databases. Comparative nucleotide
      and protein sequence analysis, in addition to available data on phage morphology,
      allowed us to propose three new phage genera within the family Siphoviridae:
      "3alikevirus", "77likevirus" and "Phietalikevirus", which include related phages
      infecting Staphylococcus aureus and Staphylococcus epidermidis. However, six
      phages infecting S. aureus, Staphylococcus pasteuri, Staphylococcus hominis and
      Staphylococcus capitis strains remain to be classified (orphan phages). Overall,
      the former phages share morphological features and genome organization. The three
      groups have conserved domains containing peptidoglycan hydrolytic activities
      clearly identified as part of tape measure proteins ("3alikevirus" and
      "77likevirus") or as individual virionassociated proteins ("Phietalikevirus"). In
      addition, bacteriophages belonging to the genus "3alikevirus" share closely
      related DNA-processing and packaging proteins, while bacteriophages included in
      the genus "Phietalikevirus" encode specific tail proteins for host interaction.
      These properties are considered distinctive for these genera. Orphan phages seem
      to have a more divergent organization, but they share some properties with
      members of these proposed genera.

PMID- 24022641
TI  - The nucleolus-guardian of cellular homeostasis and genome integrity.
AB  - All organisms sense and respond to conditions that stress their homeostasis by
      downregulating the synthesis of rRNA and ribosome biogenesis, thus designating
      the nucleolus as the central hub in coordinating the cellular stress response.
      One of the most intriguing roles of the nucleolus, long regarded as a mere
      ribosome-producing factory, is its participation in monitoring cellular stress
      signals and transmitting them to the RNA polymerase I (Pol I) transcription
      machinery. As rRNA synthesis is a most energy-consuming process, switching off
      transcription of rRNA genes is an effective way of saving the energy required to
      maintain cellular homeostasis during acute stress. The Pol I transcription
      machinery is the key convergence point that collects and integrates a vast array
      of information from cellular signaling cascades to regulate ribosome production
      which, in turn, guides cell growth and proliferation. This review focuses on the
      mechanisms that link cell physiology to rDNA silencing, a prerequisite for
      nucleolar integrity and cell survival.

PMID- 24022642
TI  - T300A variant of autophagy ATG16L1 gene is associated with decreased antigen
      sampling and processing by dendritic cells in pediatric Crohn's disease.
AB  - BACKGROUND: The single-nucleotide polymorphism T300A of ATG16L1, a Crohn's
      disease (CD)-associated gene, is responsible for decreased autophagy. This study
      aimed to investigate the effects of this single-nucleotide polymorphism on the
      uptake and processing of antigens by dendritic cells (DCs) and the interaction
      between DC and intestinal epithelium in pediatric patients with CD. METHODS:
      Pediatric patients who homozygously carry either the protective (wild type, n =
      7) or risk allele (risk, n = 13) of ATG16L1, as well as heterozygous patients
      (het, n = 13) were enrolled. The monocyte-derived DC were analyzed for phenotype,
      antigen sampling, and processing by flow cytometry, whereas the capability of DC
      to form transepithelial protrusions was determined by confocal microscopy.
      RESULTS: DC generated from wild type patients showed higher bacteria sampling and
      antigen processing compared with risk patients. Additionally, after exposure to
      either bacteria particles or the antigen DQ-ovalbumin, wild type DC showed a
      significant increase in the expression of the HLA-DR and CD86 when compared with
      risk DC. Interestingly, also het patients showed an impairment in bacteria uptake
      and expression of activation marker when compared with the wild type. In the
      Caco2/DC coculture, the formation of transepithelial protrusions were less
      numerous in risk DC compared with wild type and the antigen uptake decreased.
      CONCLUSIONS: DC of pediatric patients with CD carrying the T300A allele showed a
      marked impairment of antigen uptake and processing and defective interactions
      between DC and intestinal epithelium. Collectively, our results suggest that an
      autophagy defect is associated with an impairment of intestinal innate immunity
      in pediatric CD.

PMID- 24022643
TI  - Assessing the effects of ketorolac and acetazolamide  on macular thickness by
      optical coherence tomography  following cataract surgery.
AB  - We aimed to evaluate the efficacy of topical ketorolac 0.5 % solution and oral
      acetazolamide 250 mg/day delivery during the first month after uneventful
      phacoemulsification surgery by measuring the macular thickness using optical
      coherence tomography. Our nonmasked randomized prospective study comprised 87
      eyes of 80 patients. Complete follow-up was achieved on 84 eyes of 77 eligible
      patients. Postoperatively, the patients were divided into three groups. One group
      received ketorolac 0.5 %, the other group received acetazolamide 250 mg/day, and
      the control group was given no agent. Macular thickness and volume were measured
      at 1 week and 1 month after surgery by optical coherence tomography. Foveal
      thickness, parafoveal thickness, and perifoveal thickness were determined to be
      significantly elevated at postoperative 1 week and 1 month in the control group.
      Foveal, perifoveal, and parafoveal volumes were also significantly high at
      postoperative week 1 and month 1 in the control group. There was no significant
      difference between the ketorolac and acetazolamide groups. The correlation
      analysis between best-corrected visual acuity, and volume and thickness revealed
      a negative correlation in the acetazolamide group. Use of acetazolamide after
      cataract surgery is as effective as ketorolac on macular thickness and volume.

PMID- 24022644
TI  - Isolated ocular Jarisch-Herxheimer reaction after initiating tuberculostatic
      therapy in a child.
AB  - After being exposed to a kindergarten teacher with infectious pulmonary
      tuberculosis, a7-year-old girl with a positive tuberculin skin test was treated
      with isoniazid. 3 days after initiation of the tuberculostatic therapy, the girl
      was referred to our hospital with an acute onset of blurred vision. Visual acuity
      (VA) was 20/200 in both eyes. Examination revealed mild anterior chamber
      inflammation, optic disc swelling, cystoid macular edema and periphlebitis in
      both eyes. However, although active tuberculosis was ruled out, the interferon
      gamma release assay was positive. The anti-tuberculosis therapy was intensified
      with pyrazinamide, isoniazid, rifampicin and methylprednisolone. Within 10 days
      we saw a resolution of the macular edema and VA was 20/25. The paradoxical
      worsening of the patient's condition after initiation of tuberculostatic therapy
      with isoniazid and the prompt response to systemic steroids are typical for
      Jarisch-Herxheimer reaction (JHR). Our patient presented no symptoms before the
      isoniazid therapy was started and the reaction was ocular without any generalized
      symptoms. This is unique among all other reported cases of ocular JHR.

PMID- 24022645
TI  - Recurrent Vogt-Koyanagi-Harada disease  with sensorineural hearing loss and
      choroidal thickening.
AB  - We report a case of Vogt-Koyanagi-Harada (VKH) disease that recurred with
      sensorineural hearing loss and choroidal thickening. We measured the choroidal
      thickness using enhanced-depth imaging optical coherence tomography (EDI-OCT) in
      a patient with VKH during corticosteroid-tapering therapy. A71-year-old male
      presented with fever, headache, and anorthopia associated with wavy choroidal
      folds and aserous retinal detachment (SRD). The EDI-OCT images showed choroidal
      thickening ([600 l m at the subfovea), and he was diagnosed with VKH disease.
      After treatment with pulsed intravenous methylprednisolone, the choroidal folds
      and SRD resolved and the choroidal thickness decreased. About 6 months after
      subsequent treatment with an oral corticosteroid started, headache, tinnitus, and
      sensorineural hearing loss developed, and increased choroidal thickness was
      observed without other evidence of increased ocular inflammation. A high-dose
      corticosteroid was injected and tapered, and the sensorineural hearing loss
      improved immediately and the choroidal thickness decreased. In the current case,
      sensorineural hearing loss occurred with recurrent VKH disease;however, there
      were no ocular inflammatory signs except for rebound choroidal thickening.
      Measuring the choroidal thickness using EDI-OCT can sensitively identify
      recurrent VKH disease.

PMID- 24022647
TI  - Molecular rectangles from platinum(II) and bridging dicarbene, diisocyanide and
      4,4'-bipyridine ligands.
AB  - A series of benzobisimidazolium salts have been prepared and treated with
      [PtCl2(dppe)] or [PtCl2(dmpe)] in the presence of sodium acetate to yield
      dinuclear dicarbene-bridged complexes of the type
      [(P^P)(X)Pt(benzodicarbene)Pt(X)(P^P)](X)2 [5]Br2-[11]I2. The reaction of
      compounds [7]Br2 and [11]I2 with AgPF6 in acetonitrile led to the exchange of the
      metal-bound bromo or iodo ligands for acetonitrile and the formation of complexes
      [(dmpe)(MeCN)Pt(benzodicarbene)Pt(MeCN)(dmpe)](PF6)4 [12](PF6)4 and [13](PF6)4.
      The dinuclear complex [13](PF6)4 reacts with 4,4'-bipyridine (4,4'-bipy) to give
      the molecular rectangle [15](PF6)8 featuring two bridging dicarbene and two
      bridging 4,4'-bipy ligands. Complex [13](PF6)4 also reacts with beta,beta'
      bis(triisopropylsiloxy)phenyl-1,4-diisocyanide 16 followed by hydrolysis of the
      Si-O bonds and intramolecular carbene formation to yield the molecular square
      [18](BF4)8 featuring bridging NR,NR- and NH,O-substituted dicarbene ligands.
      Reaction of the dinuclear complex [12](PF6)4 containing a sterically demanding
      N,N',N'',N'''-substituted dicarbene ligand under otherwise identical reaction
      conditions did not lead to any molecular rectangles. The molecular square
      [19](BF4)8 was synthesized from beta,beta'-bis(triisopropylsiloxy)phenyl-1,4
      diisocyanide 16 and [PtCl2(dmpe)] in the presence of AgBF4. It reacts to yield
      the molecular square [20](BF4)8 with four NH,O-substituted dicarbene ligands by
      Si-O bond cleavage and subsequent intramolecular cyclization. 

PMID- 24022646
TI  - A surgical model for isolating the pig liver in vivo for gene therapy.
AB  - Several studies report results that suggest the need of vascularization blocking
      for efficient gene transfer to the liver, especially in nonviral gene therapy. In
      this study, we describe a surgical strategy for in vivo isolation of the pig
      liver, resulting in a vascular watertight organ that allows the evaluation of
      several gene injection conditions. The hepatic artery and portal, suprahepatic
      and infrahepatic cava veins were dissected. Then, liver vascularization was
      excluded for 5-7 min. In that time, we first injected 200 ml saline solution
      containing the p3c-eGFP plasmid (20 ug/ml) simultaneously through two different
      catheters placed in the portal and cava veins, respectively. Vital constants were
      monitored during the surgery to assess the safety of the procedure. Basal
      systolic/diastolic blood pressures were 92.8/63.2 mm Hg and dropped to 40.7/31.3
      mm Hg at the end of vascular exclusion; the mean basal heart rate was 58 bpm,
      reaching 95 bpm when the blood pressure was low. Oxygen saturation was maintained
      above 98% during the intervention, and no relevant changes were observed in the
      ECG tracing. Peak plasma AST (aspartate aminotransferase) and ALT (alanine
      aminotransferase) levels were observed after 24 h (151 and 57 IU, respectively).
      These values were higher, but not relevant, in 60 ml/s injection than in 20 ml/s
      injection. Efficiency of gene transfer was studied with simultaneous (cava and
      portal veins) injection of eGFP gene at flow rates of 20 and 60 ml/s. Liver
      tissue samples were collected 24 h after injection and qPCR was carried out on
      each lobe sample. The results confirmed the efficiency of the procedure. Gene
      delivery differed between 20 ml/s (9.9-31.0 eGFP DNA copies/100 pg of total DNA)
      and 60 ml/s injections (0.6-1.1 eGFP DNA copies/100 pg of total DNA). Gene
      transcription showed no significant differences between 20 ml/s (15,701.8
      21,475.8 eGFP RNA copies/100 ng of total RNA) and 60 ml/s (12,014-36,371 eGFP RNA
      copies/100 ng of total RNA). The procedure is not harmful for animals and it
      offers a wide range of gene delivery options because it allows different
      perfusion ways (anterograde and retrograde) and different flow rates to determine
      the optimal conditions of gene transfer. This strategy permits the use of cell
      therapy and viral or non-viral liver gene therapy, especially appropriated to a
      wide variety of inherited or acquired diseases because of the liver's ability to
      produce and deliver proteins to the bloodstream.

PMID- 24022648
TI  - The hippo tumor suppressor network: from organ size control to stem cells and
      cancer.

PMID- 24022649
TI  - Talking to children matters: early language experience strengthens processing and
      builds vocabulary.
AB  - Infants differ substantially in their rates of language growth, and slow growth
      predicts later academic difficulties. In this study, we explored how the amount
      of speech directed to infants in Spanish-speaking families low in socioeconomic
      status influenced the development of children's skill in real-time language
      processing and vocabulary learning. All-day recordings of parent-infant
      interactions at home revealed striking variability among families in how much
      speech caregivers addressed to their child. Infants who experienced more child
      directed speech became more efficient in processing familiar words in real time
      and had larger expressive vocabularies by the age of 24 months, although speech
      simply overheard by the child was unrelated to vocabulary outcomes. Mediation
      analyses showed that the effect of child-directed speech on expressive vocabulary
      was explained by infants' language-processing efficiency, which suggests that
      richer language experience strengthens processing skills that facilitate language
      growth. 

PMID- 24022650
TI  - Behavioral confirmation of everyday sadism.
AB  - Past research on socially aversive personalities has focused on subclinical
      psychopathy, subclinical narcissism, and Machiavellianism-the "Dark Triad" of
      personality. In the research reported here, we evaluated whether an everyday form
      of sadism should be added to that list. Acts of apparent cruelty were captured
      using two laboratory procedures, and we showed that such behavior could be
      predicted with two measures of sadistic personality. Study 1 featured a bug
      killing paradigm. As expected, sadists volunteered to kill bugs at greater rates
      than did nonsadists. Study 2 examined willingness to harm an innocent victim.
      When aggression was easy, sadism and Dark Triad measures predicted unprovoked
      aggression. However, only sadists were willing to work for the opportunity to
      hurt an innocent person. In both studies, sadism emerged as an independent
      predictor of behavior reflecting an appetite for cruelty. Together, these
      findings support the construct validity of everyday sadism and its incorporation
      into a new "Dark Tetrad" of personality. 

PMID- 24022651
TI  - Other people as means to a safe end: vicarious extinction blocks the return of
      learned fear.
AB  - Information about what is dangerous and safe in the environment is often
      transferred from other individuals through social forms of learning, such as
      observation. Past research has focused on the observational, or vicarious,
      acquisition of fears, but little is known about how social information can
      promote safety learning. To address this issue, we studied the effects of
      vicarious-extinction learning on the recovery of conditioned fear. Compared with
      a standard extinction procedure, vicarious extinction promoted better extinction
      and effectively blocked the return of previously learned fear. We confirmed that
      these effects could not be attributed to the presence of a learning model per se
      but were specifically driven by the model's experience of safety. Our results
      confirm that vicarious and direct emotional learning share important
      characteristics but that social-safety information promotes superior down
      regulation of learned fear. These findings have implications for emotional
      learning, social-affective processes, and clinical practice. 

PMID- 24022652
TI  - A Bafri, un Pafri: bilinguals' Pseudoword identifications support language
      specific phonetic systems.
AB  - Bilinguals perceptually accommodate speech variation across languages, but to
      what extent this flexibility depends on bilingual experience is uncertain. One
      account suggests that bilingual experience promotes language-specific processing
      modes, implying that bilinguals can switch as appropriate between the different
      phonetic systems of the languages they speak. Another account suggests that
      bilinguals rapidly recalibrate to the unique acoustic properties of each language
      following language-general processes common to monolinguals. Challenging this
      latter account, the present results show that Spanish-English bilinguals with
      exposure to both languages from early childhood, but not English monolinguals,
      shift perception as appropriate across acoustically controlled English and
      Spanish contexts. Early bilingual experience appears to promote language-specific
      phonetic systems. 

PMID- 24022653
TI  - The future is now: reducing impulsivity and energy intake using episodic future
      thinking.

PMID- 24022654
TI  - In vitro mimics of bone remodeling and the vicious cycle of cancer in bone.
AB  - Bone remodeling is a natural process that enables growth and maintenance of the
      skeleton. It involves the deposition of mineralized matrix by osteoblasts and
      resorption by osteoclasts. Several cancers that metastasize to bone negatively
      perturb the remodeling process through a series of interactions with osteoclasts,
      and osteoblasts. These interactions have been described as the "vicious cycle" of
      cancer metastasis in bone. Due to the inaccessibility of the skeletal tissue, it
      is difficult to study this system in vivo. In contrast, standard tissue culture
      lacks sufficient complexity. We have developed a specialized three-dimensional
      culture system that permits growth of a non-vascularized, multiple-cell-layer of
      mineralized osteoblastic tissue from pre-osteoblasts. In this study, the
      essential properties of bone remodeling were created in vitro by co-culturing the
      mineralized collagenous osteoblastic tissue with actively resorbing osteoclasts
      followed by reinfusion with proliferating pre-osteoblasts. Cell-cell and cell
      matrix interactions were determined by confocal microscopy as well as by assays
      for cell specific cytokines and growth factors. Osteoclasts, differentiated in
      the presence of osteoblasts, led to degradation of the collagen-rich
      extracellular matrix. Further addition of metastatic breast cancer cells to the
      co-culture mimicked the vicious cycle; there was a further reduction in
      osteoblastic tissue thickness, an increase in osteoclastogenesis, chemotaxis of
      cancer cells to osteoclasts and formation of cancer cells into large colonies.
      The resulting model system permits detailed study of fundamental osteobiological
      and osteopathological processes in a manner that will enhance development of
      therapeutic interventions to skeletal diseases.

PMID- 24022656
TI  - Investigation of the surface chemistry of phosphine-stabilized ruthenium
      nanoparticles--an advanced solid-state NMR study.
AB  - (31)P-(13)C REDOR NMR measurements allowed a reasonable approximation of
      distances between stabilizing ligands and carbon monoxide (CO) molecules on the
      surface of phosphine-stabilized ruthenium nanoparticles (RuNPs). The studied
      systems are RuNPs in the size range of 1-2 nm stabilized with 1,3,5-triaza-7
      phosphaadamantane (PTA) or triphenylphosphine (PPh3) and exposed to a CO
      atmosphere. This study sheds some light on the interactions between CO and
      phosphine molecules as well as on their binding geometries on the surface of the
      RuNPs. As information on the ligand location and mobility is precious for the
      understanding of the chemical and catalytic properties of nanoparticles, these
      results support the interest of using sophisticated NMR tools to investigate
      their surface chemistry. 

PMID- 24022655
TI  - Gold standard program for heavy smokers in a real-life setting.
AB  - BACKGROUND: High-intensity smoking cessation programs generally lead to more
      continuous abstinence, however, lower rates of success have been reported among
      heavy smokers. The aim was to evaluate continuous abstinence among heavy smokers
      during the intensive 6-week Gold Standard Program (GSP) and to identify
      modifiable factors associated with continuous abstinence. METHODS: In this
      nationwide clinical study based on 36,550 smokers attending an intensive
      cessation program in Denmark. Heavy smoking was defined as >=7 points in the
      Fagerstrom Nicotine Dependency Test, smoking >=20 cigarettes daily or >=20 pack
      years. RESULTS: Overall, 28% had a Fagerstrom score >=7 points, 58% smoked >=20
      cigarettes daily and 68% smoked >=20 pack-years. Continuous abstinence was 33% in
      responders (6-months response rate: 78%); however, abstinence was approximately 1
      6% lower in the heavy smokers than the overall population. Attending GSP with an
      individual format (vs. group/other, OR 1.23-1.44); in a hospital setting (vs.
      pharmacy/municipality services, OR 1.05-1.11); and being compliant (attending the
      planned meetings OR 4.36-4.89) were associated with abstinence. Abstinence
      decreased in a dose-dependent manner with increasing smoking severity.
      CONCLUSIONS: Abstinence after GSP was 1-6% lower in the heavy smokers than in the
      overall study population. Modifiable factors may be used for small improvements
      in continued abstinence. However attempts to improve compliance seemed especially
      promising.

PMID- 24022657
TI  - Renal capsule xenografting and subcutaneous pellet implantation for the
      evaluation of prostate carcinogenesis and benign prostatic hyperplasia.
AB  - New therapies for two common prostate diseases, prostate cancer (PrCa) and benign
      prostatic hyperplasia (BPH), depend critically on experiments evaluating their
      hormonal regulation. Sex steroid hormones (notably androgens and estrogens) are
      important in PrCa and BPH; we probe their respective roles in inducing prostate
      growth and carcinogenesis in mice with experiments using compressed hormone
      pellets. Hormone and/or drug pellets are easily manufactured with a pellet press,
      and surgically implanted into the subcutaneous tissue of the male mouse host. We
      also describe a protocol for the evaluation of hormonal carcinogenesis by
      combining subcutaneous hormone pellet implantation with xenografting of prostate
      cell recombinants under the renal capsule of immunocompromised mice. Moreover,
      subcutaneous hormone pellet implantation, in combination with renal capsule
      xenografting of BPH tissue, is useful to better understand hormonal regulation of
      benign prostate growth, and to test new therapies targeting sex steroid hormone
      pathways. 

PMID- 24022658
TI  - Neurologic complications of infective endocarditis.
AB  - Infective endocarditis is an infection of the inner surface or endocardium of the
      heart, in most instances involving the heart valves or the mural portion of the
      endocardium. As nonbacterial organisms such as rickettsia, fungi, and even
      viruses may also cause endocarditis, the term "infective endocarditis" is
      preferred over the older terminology of "bacterial endocarditis." Despite
      advancements in medical treatment and surgical therapies over the last few
      decades, infective endocarditis continues to be associated with a poor prognosis.
      There are many different factors affecting the clinical outcome in patient with
      infective endocarditis, including the type of organism and its virulence, patient
      characteristics, comorbid illness, time to diagnosis and treatment, indications
      for surgery, and time to surgery when indicated. In this article, we will review
      the epidemiology of endocarditis, the neurologic complications of infective
      endocarditis, and the current therapeutic strategies.

PMID- 24022659
TI  - Insulin resistance is a major determinant of myocardial blood flow impairment in
      anginal patients.
AB  - PURPOSE: In patients with chest pain, stress-induced myocardial perfusion
      abnormalities are often the result of depressed myocardial blood flow (MBF)
      reserve. We investigated the relative contribution of cardiovascular risk factors
      and coronary atherosclerosis to MBF abnormalities in anginal patients. METHODS:
      We studied 167 patients with typical (n = 100) or atypical (n = 67) chest pain
      who underwent quantitative evaluation of MBF by PET at rest and after
      dipyridamole infusion, and quantitative coronary angiography (invasive or by 64
      slice CT). Patients with left ventricular (LV) dysfunction (ejection fraction <45
      %) were excluded. Coronary atherosclerosis of >=50 % was defined as obstructive.
      RESULTS: At rest median MBF was 0.60 ml min-1 g-1, and after dipyridamole
      infusion median MBF was 1.22 ml min-1 g-1. MBF reserve was <2 in 77 of 167
      patients (46 %). Coronary atherosclerosis was present in 67 patients (40 %), 26
      with obstructive disease. In a univariate analysis several variables were
      associated with reduced MBF at rest, including male gender, coronary
      atherosclerosis and elevated LV end-diastolic diameter, and during hyperaemia,
      including male gender, insulin resistance (IR), smoking habit, LV ejection
      fraction and end-diastolic diameter. In a multivariate analysis, after adjustment
      for LV function and for pharmacological treatments, male gender was the only
      independent predictor of reduced MBF at rest (P < 0.001), while male gender (P =
      0.003), IR (P = 0.033) and coronary atherosclerosis (P < 0.001) remained the only
      independent predictors of reduced hyperaemic MBF. IR (P = 0.043) and coronary
      atherosclerosis (P = 0.005) were the only predictors of depressed MBF reserve.
      Coronary atherosclerosis, male gender and IR showed additive effects on
      hyperaemic MBF. CONCLUSION: In patients with chest pain and normal LV systolic
      function, IR, male gender and coronary atherosclerosis are independent and
      additive determinants of impaired hyperaemic MBF.

PMID- 24022660
TI  - Long-term treatment with mammalian target of rapamycin inhibitor does not benefit
      patients with autosomal dominant polycystic kidney disease: a meta-analysis.
AB  - BACKGROUND: The role of the mammalian target of rapamycin (mTOR) inhibition in
      the treatment of autosomal dominant polycystic kidney disease (ADPKD) remains
      unclear. This meta-analysis included all randomized controlled trials (RCTs) that
      used mTOR inhibitors (TORIs) to halt the progression of ADPKD. METHODS: Databases
      including MEDLINE, EMBASE, and the Cochrane Library were searched to find
      relevant trials. RCTs of TORI treatment in patients with ADPKD were included.
      Effects on the primary outcome [total kidney volume (TKV)] and secondary outcomes
      [changes in cyst volume (CV) and parenchymal volume (PV), glomerular filtration
      rate (GFR), proteinuria, and adverse events] were analyzed. RESULTS: The results
      of 5 RCTs, which included 619 patients, were analyzed. TORIs did not
      significantly reduce TKV [mean difference (WMD) -90.01 ml, 95% CI -235.49 to
      55.47, p = 0.23; I(2) = 0%; p for heterogeneity = 0.67]. CV decreased after TORI
      treatment (WMD -15.08 ml, 95% CI -17.82 to -12.34, p < 0.00001), and PV did not
      change (WMD -0.55 ml, 95% CI -64.55 to 63.45, p = 0.99). There was no significant
      difference in GFR between the TORI-treated and control groups (WMD 4.94 ml/min,
      95% CI -0.81 to 10.68, p = 0.09). Proteinuria was significantly higher in the
      TORI-treated group than in the control group (standard mean difference 0.27, 95%
      CI 0.09-0.44, p = 0.002). CONCLUSION: Long-term treatment with TORIs does not
      benefit patients with ADPKD.

PMID- 24022662
TI  - Effect of GSTM1 null genotype on risk of childhood acute leukemia: a meta
      analysis.
AB  - Glutathione S-transferases are important enzymes in the detoxification of a wide
      range of reactive oxygen species. Recently, there have been a number of studies
      on the association between Glutathione S-transferase M1 (GSTM1) null genotype and
      childhood acute leukemia in Chinese, but the results of previous reports are
      inconsistent. Thus, we performed a meta-analysis to clarify the effect of GSTM1
      null genotype on childhood acute leukemia risk. PubMed, Embase, and Wanfang
      databases were searched to identify case-control studies investigating the
      association between GSTM1 null genotype and risk of childhood acute leukemia.
      Between-study heterogeneity was assessed using the I2 statistic method. Odds
      ratios (OR) with corresponding 95% confidence intervals (95% CI) were pooled to
      assess the association. Seven case-control studies were finally included in the
      meta-analysis. There was no between-study heterogeneity among those seven studies
      (I2 = 0%). Overall, the GSTM1 null genotype was significantly associated with
      increased risk of childhood acute leukemia in Chinese (fixed effect OR = 2.49;
      95% CI, 1.84-3.37; P < 0.001). The cumulative meta-analyses showed a trend of
      more obvious association between GSTM1 null genotype and risk of childhood acute
      leukemia in Chinese as data accumulated by year. Sensitivity analysis by omitting
      single study in turns also did not materially alter the pooled ORs. Therefore,
      the GSTM1 null genotype is significantly associated with increased risk of
      childhood acute leukemia in Chinese.

PMID- 24022663
TI  - Association between glutathione S-transferase M1 null variant and risk of bladder
      cancer in Chinese Han population.
AB  - Glutathione S-transferase M1 (GSTM1) is one of the most important families of
      phase II isoenzymes known to detoxify a variety of electrophilic compounds and
      carcinogens. The GSTM1 null variant is associated with decreased enzyme activity,
      and it has been assumed to be associated with bladder cancer. The association
      between the GSTM1 null variant and bladder cancer in the Chinese Han population
      was unclear owing to the obvious inconsistency from published studies. To
      quantify the association between the GSTM1 null variant and bladder cancer in the
      Chinese Han population, we carried out the meta-analysis. We estimated the pooled
      odds ratio (OR) with its 95% confidence interval (95% CI) to assess the
      association. Eight studies with a total of 3,887 individuals were finally
      included into the meta-analysis. Overall, there was an obvious association
      between the GSTM1 null variant and risk of bladder cancer in the Chinese Han
      population (OR = 1.61, 95% CI 1.41-1.84, P < 0.001). There was no heterogeneity
      across those eight studies (I 2 = 0%). The cumulative meta-analyses showed a
      trend of more obvious association between the GSTM1 null variant and risk of
      bladder cancer in the Chinese Han population as data accumulated by year. There
      was no obvious evidence of publication bias in the meta-analysis. In conclusion,
      the GSTM1 null variant is significantly associated with risk of bladder cancer in
      the Chinese Han population.

PMID- 24022661
TI  - P2X7 blockade attenuates murine lupus nephritis by inhibiting activation of the
      NLRP3/ASC/caspase 1 pathway.
AB  - OBJECTIVE: The NLRP3 inflammasome plays key roles in inflammation and
      autoimmunity, and purinergic receptor P2X7 has been proposed to be upstream of
      NLRP3 activation. The aim of the present study, using murine models, was to
      investigate whether the P2X7 /NLRP3 inflammasome pathway contributes to the
      pathogenesis of lupus nephritis (LN). METHODS: MRL/lpr mice were treated with the
      selective P2X7 antagonist brilliant blue G (BBG) for 8 weeks. Following
      treatment, the severity of renal lesions, production of anti-double-stranded DNA
      (anti-dsDNA) antibodies, rate of survival, activation of the NLRP3/ASC/caspase 1
      inflammasome pathway, and ratio of Th17 cells to Treg cells were evaluated. P2X7 
      targeted small interfering RNA (siRNA) was also used for in vivo intervention.
      Similar evaluations were carried out in NZM2328 mice, a model of LN in which the
      disease was accelerated by administration of adenovirus-expressing interferon
      alpha (AdIFNalpha). RESULTS: Significant up-regulation of P2X7 /NLRP3
      inflammasome signaling molecules was detected in the kidneys of MLR/lpr mice as
      compared with normal control mice. Blockade of P2X7 activation by BBG suppressed
      NLRP3/ASC/caspase 1 assembly and the subsequent release of interleukin-1beta (IL
      1beta), resulting in a significant reduction in the severity of nephritis and
      circulating anti-dsDNA antibodies. The lifespan of the treated mice was
      significantly prolonged. BBG treatment reduced the serum levels of IL-1beta and
      IL-17 and the Th17:Treg cell ratio. Similar results were obtained by specific
      siRNA silencing of P2X7 in vivo. The effectiveness of BBG treatment in modulating
      LN was confirmed in NZM2328 mice with AdIFNalpha-accelerated disease. CONCLUSION:
      Activation of the P2X7 signaling pathway accelerates murine LN by activating the
      NLRP3/ASC/caspase 1 inflammasome, resulting in increased IL-1beta production and
      enhanced Th17 cell polarization. Thus, targeting of the P2X7 /NLRP3 pathway
      should be considered as a novel therapeutic strategy in patients with lupus.

PMID- 24022664
TI  - The tumor suppressor LKB1 antagonizes WNT signaling pathway through modulating
      GSK3beta activity in cell growth of esophageal carcinoma.
AB  - The tumor suppressor LKB1 gene encodes a serine-threonine kinase that regulates
      cell proliferation and polarity. Inactivation of LKB1 by mutations in LKB1 or
      loss of its expression is highly correlated with lung, ovarian, and pancreatic
      cancers, and WNT/beta-catenin pathway is also known to be involved in many human
      malignancies. However, the relationship between LKB1 and WNT signaling pathway in
      esophageal carcinoma remains unknown. The expression of LKB1 in 62 cases of
      esophageal cancer patients was determined by quantitative real-time PCR. It was
      found that LKB1 mRNA level was significantly lower than the adjacent normal
      epithelium and that the LKB1 downregulation was correlating with TNM stages.
      Moreover, the expression of WNT target genes such as Cyclin D1, C-MYC, MMP2, and
      FZD2 was significantly upregulated in esophageal cancer tissues. LKB1
      overexpression in TE10 cells inhibited TOPFlash luciferase reporter activity and
      WNT target gene expression even in the presence of WNT3A. Conversely, LKB1
      knockdown enhanced WNT signaling activity in esophageal cancer cells. It was also
      found that LKB1 antagonized WNT signaling pathway through interaction with
      GSK3beta to downregulate beta-catenin expression level. Functional investigation
      revealed that LKB1 suppressed the promotion effects of WNT3A on the cell growth
      of TE10 cells. The LKB1 functions in regulating cell growth and WNT target genes
      expression were impaired by GSK3beta inhibition, suggesting that LKB1 antagonized
      WNT-induced cell proliferation through enhancement of GSK3beta activity.
      Together, the interaction between LKB1 and GSK3beta upregulates GSK3beta activity
      to suppress WNT-induced cell proliferation in esophageal carcinoma cells. Loss of
      LKB1 expression may result in the deregulation of WNT/beta-catenin pathway to
      promote malignant progression of esophageal cancer.

PMID- 24022665
TI  - Notch-1-mediated esophageal carcinoma EC-9706 cell invasion and metastasis by
      inducing epithelial-mesenchymal transition through Snail.
AB  - Notch has recently been shown to promote epithelial-to-mesenchymal transition
      (EMT) by involving in the EMT process that occurs during tumor progression and
      converts polarized epithelial cells into motile, invasive cells. However, it is
      still unclear whether the Notch signaling pathway is associated with the
      regulation of EMT in esophageal carcinoma. The present study explored Notch-1
      mediated esophageal carcinoma EC-9706 cell invasion and metastasis by inducing
      epithelial-mesenchymal transition through Snail. The results demonstrated that
      the inhibition of Notch-1 expression in the esophageal carcinoma cell line EC
      9706 could suppress the occurrence of EMT and at the same time could decrease the
      invasion and metastasis ability of the EC-9706 cells, indicative of its role in
      EMT. Snail is a transcriptional repressor of E-cadherin. We found that with the
      inhibition of Notch-1 expression in the esophageal carcinoma cell line EC-9706,
      the expression of Snail also decreased. Mechanistic studies showed that the up
      expression of Snail in the EC-9706 cells restored the suppression of EMT
      regulated by Notch-1 inhibition, suggesting the role of Snail in Notch-1-mediated
      EMT. At the same time, the up-expression of Snail in the EC-9706 cells could also
      rescue the invasion and metastasis ability inhibited by Notch-1 siRNA. Taken
      together, our results had revealed that Notch-1 could participate in the invasion
      and metastasis of esophageal carcinoma through EMT via Snail. This study
      indicated that Notch-1 might be a useful target for esophageal carcinoma
      prevention and therapy.

PMID- 24022666
TI  - Para versus meta ligand substituents as a means of directing magnetic anisotropy
      in Fe2Dy2 coordination clusters.
AB  - The modulation of the magnetic anisotropy using the electronic features of the
      ligands was monitored by performing magnetic, spectroscopic and theoretical
      studies on a series of {Fe2Dy2} coordination clusters. 

PMID- 24022667
TI  - Foraging ants trade off further for faster: use of natural bridges and trunk
      trail permanency in carpenter ants.
AB  - Trail-making ants lay pheromones on the substrate to define paths between
      foraging areas and the nest. Combined with the chemistry of these pheromone
      trails and the physics of evaporation, trail-laying and trail-following
      behaviours provide ant colonies with the quickest routes to food. In relatively
      uniform environments, such as that provided in many laboratory studies of trail
      making ants, the quickest route is also often the shortest route. Here, we show
      that carpenter ants (Camponotus rufipes), in natural conditions, are able to make
      use of apparent obstacles in their environment to assist in finding the fastest
      routes to food. These ants make extensive use of fallen branches, twigs and
      lianas as bridges to build their trails. These bridges make trails significantly
      longer than their straight line equivalents across the forest floor, but we
      estimate that ants spend less than half the time to reach the same point, due to
      increased carriage speed across the bridges. We also found that these trails,
      mainly composed of bridges, are maintained for months, so they can be
      characterized as trunk trails. We suggest that pheromone-based foraging trail
      networks in field conditions are likely to be structured by a range of
      potentially complex factors but that even then, speed remains the most important
      consideration.

PMID- 24022668
TI  - Variable coordination of redox-active TCNB in discrete and polymeric
      ferrocenylcopper(I) complexes: structures and spectroelectrochemical behaviour.
AB  - 1,2,4,5-Tetracyanobenzene (TCNB) was reacted with [Cu(dppf)(CH3CN)2](BF4) and
      [Cu(dchpf)(CH3CN)](BF4), dppf = 1,1'-bis(diphenylphosphino)ferrocene and dchpf =
      1,1'-bis(dicyclohexylphosphino)ferrocene, to produce a heterotetranuclear
      metallamacrocycle 1, {[Cu(dppf)(MU-TCNB)](BF4)}2, and a heterooctanuclear complex
      2, [{Cu(dchpf)}4(MU4-TCNB)](BF4)4. Complex 1 is the first example of a
      structurally characterised discrete transition metal complex of TCNB. Upon
      crystallisation attempts, compound 2 formed the structurally identified
      coordination polymer 3, {[Cu(dchpf)(MU-TCNB)]2(BF4)2}n. Structural and
      spectroscopic analyses confirmed the redox-innocent behaviour of TCNB in 1, 2 and
      3. However, the soluble compounds 1 and 2 could be oxidised and reduced
      spectroelectrochemically (UV-vis, IR, and EPR). The oxidation occurs invariably
      at the ferrocene sites without notable splitting of redox potentials. Reduction
      involves the TCNB bridging ligands to produce radical complexes. As a variably
      bridging acceptor component of supramolecular structures the TCNB ligand thus
      adopts an intermediate position between the highly electron transfer-active TCNE,
      TCNQ and TCNQF4 systems and the numerous redox-innocent bridges. 

PMID- 24022669
TI  - Variability of urinary cadmium excretion in spot urine samples, first morning
      voids, and 24 h urine in a healthy non-smoking population: implications for study
      design.
AB  - When selecting the least biased exposure surrogate, for example, the
      concentration of a biomarker in a urine sample, information on variability must
      be taken into consideration. We used mixed-effects models to estimate the
      variability and determinants of urinary cadmium (U-Cd) excretion using spot urine
      samples collected at six fixed times during 2 days about 1 week apart, from 24
      healthy non-smokers. The urine samples were analysed for U-Cd, the concentrations
      were adjusted for dilution, and the excretion rates were calculated. Between
      individual variability dominated the total variability for most measures of U-Cd
      excretion, especially for 24 h urine and first morning samples. The U-Cd
      excretion showed a circadian rhythm during the day, and time point of sampling
      was a significant factor in the mixed-effects models, thus a standardised
      sampling time, such as first morning urine samples, needs to be applied. Gender,
      urinary flow rate, age, and urinary protein excretions were also significant
      determinants for U-Cd excretion. The choice of biomarker for U-Cd excretion was
      found to be more important in individually-based studies of exposure-response
      relationships than in studies of comparing Cd levels of groups. When planning a
      study, this variability of U-Cd in spot samples must be acknowledged. 

PMID- 24022670
TI  - Development of a job-exposure matrix for exposure to total and fine particulate
      matter in the aluminum industry.
AB  - Increasing evidence indicates that exposure to particulate matter (PM) at
      environmental concentrations increases the risk of cardiovascular disease,
      particularly PM with an aerodynamic diameter of less than 2.5 MUm (PM(2.5)).
      Despite this, the health impacts of higher occupational exposures to PM(2.5) have
      rarely been evaluated. In part, this research gap derives from the absence of
      information on PM(2.5) exposures in the workplace. To address this gap, we have
      developed a job-exposure matrix (JEM) to estimate exposure to two size fractions
      of PM in the aluminum industry. Measurements of total PM (TPM) and PM(2.5) were
      used to develop exposure metrics for an epidemiologic study. TPM exposures for
      distinct exposure groups (DEGs) in the JEM were calculated using 8385 personal
      TPM samples collected at 11 facilities (1980-2011). For eight of these
      facilities, simultaneous PM(2.5) and TPM personal monitoring was conducted from
      2010 to 2011 to determine the percent of TPM that is composed of PM(2.5)
      (%PM(2.5)) in each DEG. The mean TPM from the JEM was then multiplied by %PM(2.5)
      to calculate PM(2.5) exposure concentrations in each DEG. Exposures in the
      smelters were substantially higher than in fabrication units; mean TPM
      concentrations in smelters and fabrication facilities were 3.86 and 0.76 mg/m(3),
      and the corresponding mean PM(2.5) concentrations were 2.03 and 0.40 mg/m(3).
      Observed occupational exposures in this study generally exceeded environmental
      PM(2.5) concentrations by an order of magnitude.

PMID- 24022671
TI  - Indoor transformer stations and ELF magnetic field exposure: use of transformer
      structural characteristics to improve exposure assessment.
AB  - Previous studies have shown that populations of multiapartment buildings with
      indoor transformer stations may serve as a basis for improved epidemiological
      studies on the relationship between childhood leukaemia and extremely-low
      frequency (ELF) magnetic fields (MFs). This study investigated whether
      classification based on structural characteristics of the transformer stations
      would improve ELF MF exposure assessment. The data included MF measurements in
      apartments directly above transformer stations ("exposed" apartments) in 30
      buildings in Finland, and reference apartments in the same buildings. Transformer
      structural characteristics (type and location of low-voltage conductors) were
      used to classify exposed apartments into high-exposure (HE) and intermediate
      exposure (IE) categories. An exposure gradient was observed: both the time
      average MF and time above a threshold (0.4 MUT) were highest in the HE apartments
      and lowest in the reference apartments, showing a statistically significant
      trend. The differences between HE and IE apartments, however, were not
      statistically significant. A simulation exercise showed that the three-category
      classification did not perform better than a two-category classification (exposed
      and reference apartments) in detecting the existence of an increased risk.
      However, data on the structural characteristics of transformers is potentially
      useful for evaluating exposure-response relationship. 

PMID- 24022674
TI  - Do new cellulolytic enzyme preparations affect the industrial strategies for high
      solids lignocellulosic ethanol production?
AB  - Production of ethanol from lignocellulosic materials has a promising market
      potential, but the process is still only at pilot/demonstration scale due to the
      technical and economical difficulties of the process. Operating the process at
      very high solids concentrations (above 20% dry matter-DM) has proven essential
      for economic feasibility at industrial scale. Historically, simultaneous
      saccharification and fermentation (SSF) was found to give better ethanol yields
      compared to separate hydrolysis and fermentation (SHF), but data in literature
      are typically based on operating the process at low dry matter conditions. In
      this work the impact of selected enzyme preparation and processing strategy (SHF,
      presaccharification and simultaneous saccharification and fermentation-PSSF, and
      SSF) on final ethanol yield and overall performance was investigated with
      pretreated wheat straw up to 30% DM. The experiments revealed that an SSF
      strategy was indeed better than SHF when applying an older generation enzyme
      cocktail (Celluclast-Novozym 188). In case of the newer product Cellic CTec 2,
      SHF resulted in 20% higher final ethanol yield compared to SSF. It was possible
      to close the mass balance around cellulose to around 94%, revealing that the most
      relevant products could be accounted for. One observation was the presence of
      oxidized sugar (gluconic acid) upon enzymatic hydrolysis with the latest enzyme
      preparation. Experiments showed gluconic acid formation by recently discovered
      enzymatic class of lytic polysaccharides monoxygenases (LPMO's) to be depending
      on the processing strategy. The lowest concentration was achieved in SSF, which
      could be correlated with less available oxygen due to simultaneous oxygen
      consumption by the yeast. Quantity of glycerol and cell mass was also depending
      on the selected processing strategy.

PMID- 24022672
TI  - 7,8-dihydroxyflavone prevents synaptic loss and memory deficits in a mouse model
      of Alzheimer's disease.
AB  - Synaptic loss in the brain correlates well with disease severity in Alzheimer
      disease (AD). Deficits in brain-derived neurotrophic factor/tropomyosin-receptor
      kinase B (TrkB) signaling contribute to the synaptic dysfunction of AD. We have
      recently identified 7,8-dihydroxyflavone (7,8-DHF) as a potent TrkB agonist that
      displays therapeutic efficacy toward various neurological diseases. Here we
      tested the effect of 7,8-DHF on synaptic function in an AD model both in vitro
      and in vivo. 7,8-DHF protected primary neurons from Abeta-induced toxicity and
      promoted dendrite branching and synaptogenesis. Chronic oral administration of
      7,8-DHF activated TrkB signaling and prevented Abeta deposition in transgenic
      mice that coexpress five familial Alzheimer's disease mutations (5XFAD mice).
      Moreover, 7,8-DHF inhibited the loss of hippocampal synapses, restored synapse
      number and synaptic plasticity, and prevented memory deficits. These results
      suggest that 7,8-DHF represents a novel oral bioactive therapeutic agent for
      treating AD. 

PMID- 24022675
TI  - Comparative demography of two commensal macaques in India: implications for
      population status and conservation.
AB  - Rhesus and bonnet macaques are among the most common primates found in India and
      have been categorised as being of Least Concern by the IUCN. Despite the wealth
      of information on their ecology and behaviour, little attention has been paid to
      their demography or population status. We studied the demographic status of the
      two species along their common distribution zone in western, central and south
      eastern India. Bonnet macaques were largely found in forest areas whereas rhesus
      macaques were observed more often in human-dominated habitats. The troop sizes of
      the two species also tended to be largest in different habitats, bonnet macaques
      in forested areas and rhesus macaques in urban areas. We suggest that the
      presence of large numbers of rhesus macaques in anthropogenic areas in south
      eastern India is not a natural phenomenon but has been caused by human
      intervention. The bonnet macaque population has decreased in number in the common
      distribution zone, and as this species, unlike the rhesus macaque, is endemic to
      India, we strongly recommend the need to reassess its conservation status.

PMID- 24022676
TI  - Extreme-rate capable and highly stable SiCO-TiO2 hybrids for Li ion battery
      anodes.
AB  - A novel hybrid material for Li ion battery anodes, synthesized from polysiloxane
      derived SiCO and nanoparticulate TiO2, exhibited specific capacity in excess of
      850 mA h g(-1), fully recoverable capacity after cycling at severe current
      densities, as high as 20,000 mA g(-1) or 300 C rate, and exceptional stability
      beyond 1000 charge discharge cycles without capacity fading. Microscopy of the
      anodes after 3000 cycles showed no degradation or loss of materials.

PMID- 24022677
TI  - Prevention of problem behavior through annual family check-ups in early
      childhood: intervention effects from home to early elementary school.
AB  - This randomized intervention trial examined the effects of yearly Family Check
      Ups (FCUs) and tailored parent management training on parent report of problem
      behavior from age 2 to 5 years and teacher report of oppositional behavior at age
      7.5. A multiethnic risk sample of 731 families in 3 distinct geographical
      settings who were receiving assistance from the Women, Infants, and Children
      Nutritional Supplement (WIC) program were randomly assigned to a yearly FCU.
      Intention to treat (ITT) analyses were used to examine overall intervention
      effects, and complier average causal effect (CACE) modeling was used to examine
      the effects of annual intervention engagement in the FCU on parent reports of
      child problem behavior from age 2 to 5 and teacher reports of problem behavior at
      age 7.5. ITT intervention effects were found regarding parent report at ages 2 to
      5 and teacher report at age 7.5, indicating less growth in problem behavior for
      children in the intervention group than for those in the control group. CACE
      modeling of intervention engagement revealed that the effect sizes on parent- and
      teacher-reported problem behavior increased as a function of the number of yearly
      FCUs caregivers participated in. Findings suggest that embedding yearly FCU
      services within the context of social, health, and educational services in early
      childhood can potentially prevent early-onset trajectories of antisocial
      behavior. The increases in effect size with successive FCU engagement underscores
      the importance of a motivational approach to parenting support among high-risk
      families. 

PMID- 24022678
TI  - Co-expression of the Arabidopsis SOS genes enhances salt tolerance in transgenic
      tall fescue (Festuca arundinacea Schreb.).
AB  - Crop productivity is greatly affected by soil salinity; therefore, improvement in
      salinity tolerance of crops is a major goal in salt-tolerant breeding. The Salt
      Overly Sensitive (SOS) signal-transduction pathway plays a key role in ion
      homeostasis and salt tolerance in plants. Here, we report that overexpression of
      Arabidopsis thaliana SOS1+SOS2+SOS3 genes enhanced salt tolerance in tall fescue.
      The transgenic plants displayed superior growth and accumulated less Na+ and more
      K+ in roots after 350 mM NaCl treatment. Moreover, Na+ enflux, K+ influx, and
      Ca2+ influx were higher in the transgenic plants than in the wild-type plants.
      The activities of the enzyme superoxide dismutase, peroxidase, catalase, and
      proline content in the transgenic plants were significantly increased; however,
      the malondialdehyde content decreased in transgenic plants compared to the
      controls. These results suggested that co-expression of A. thaliana
      SOS1+SOS2+SOS3 genes enhanced the salt tolerance in transgenic tall fescue.

PMID- 24022679
TI  - Ultrastructure and cytochemistry of salivary  glands of the predator Podisus
      nigrispinus  (Hemiptera: Pentatomidae.
AB  - Podisus nigrispinus Dallas (Hemiptera: Pentatomidae) is a zoophytophagous insect
      with a potential for use as a biological control agent in agriculture because
      nymphs and adults actively prey on various insects by inserting mouthparts and
      regurgitating the contents of the salivary glands inside the prey, causing rapid
      paralysis and death. However, the substances found in saliva of P. nigrispinus
      that causes the death of the prey are unknown. As a first step to identify the
      component of the saliva of P. nigrispinus, this study evaluated the
      ultrastructure and cytochemistry of the salivary glands of P. nigrispinus. The
      salivary system of P. nigrispinus has a pair of principal salivary glands, which
      are bilobed with a short anterior lobe and a long posterior lobe, and a pair of
      tubular accessory glands. The principal gland epithelium is composed of a single
      layer of cells enclosing a large lumen. Epithelial cells of the principal
      salivary gland vary from cubic to columnar shape, with one or two spherical and
      well-developed nuclei. Cells of the anterior lobe of the principal salivary gland
      have an apical surface with narrow, short, and irregular plasma membrane
      foldings; apical and perinuclear cytoplasm rich in rough endoplasmic reticulum;
      and mitochondria with tubular cristae. The basal portion of the secretory cells
      has mitochondria associated with many basal plasma membrane infoldings that are
      short but form large extracellular canals. Secretory granules with electron-dense
      core and electron-transparent peripheral are dispersed throughout the cytoplasm.
      Cells of the posterior lobe of the principal salivary gland are similar to those
      of the anterior lobe, except for the presence of mitochondria with transverse
      cristae. The accessory salivary gland cells are columnar with apical microvilli,
      have well-developed nucleus and cytoplasm rich in rough endoplasmic reticulum,
      and have secretory granules. Cytochemical tests showed positive reactions for
      carbohydrate, protein, and acid phosphatase in different regions of the glandular
      system. The principal salivary glands of P. nigrispinus do not have muscle cells
      attached to its wall, suggesting that saliva-releasing mechanism may occurs with
      the participation of some thorax muscles. The cytochemical and ultrastructural
      features suggest that the principal and accessory salivary glands play a role in
      protein synthesis of the saliva.

PMID- 24022680
TI  - Impact of different vehicles for laser-assisted drug permeation via skin: full
      surface versus fractional ablation.
AB  - PURPOSE: This study aimed to assess impact of different vehicles for laser
      assisted skin drug delivery. We also tried to uncover the mechanisms by which
      different vehicles affect laser-aided skin permeation. METHODS: Full-surface
      ablative (conventional) and fractional lasers were used to irradiate nude mouse
      skin. Imiquimod and 5-aminolevulinic acid (ALA) were used as lipophilic and
      hydrophilic permeants. Vehicles employed included water with 40% polyethylene
      glycol 400 (PEG 400), propylene glycol (PG), and ethanol. Lipid nanoparticles
      were also utilized as carriers. RESULTS: In vitro permeation profiles showed
      improvement in imiquimod flux with conventional laser (2.5 J/cm2) producing a 12
      , 9-, and 5-fold increase when loading imiquimod in 40% PEG400, PG, and ethanol,
      respectively, as compared with intact skin. Nanoparticulate delivery by laser
      produced a 6-fold enhancement in permeation. Fractional laser produced less
      enhancement of imiquimod delivery than conventional laser. Laser exposure
      increased follicular imiquimod accumulation from 0.80 to 5.81 MUg/cm2. ALA
      permeation from aqueous buffer, PEG 400, and PG with conventional laser treatment
      was 641-, 445-, and 104-fold superior to passive control. In vivo skin deposition
      of topically applied ALA examined by confocal microscopy indicated the same trend
      as the in vitro experiment, with aqueous buffer showing the greatest
      proporphyllin IX signaling. Diffusion of cosolvent molecules into ablated skin
      and drug partitioning from vehicle to skin are two predominant factors
      controlling laser-assisted delivery. In contrast to conventional laser, lateral
      drug diffusion was anticipated for fractional laser. CONCLUSIONS: Our results
      suggest that different drug delivery vehicles substantially influence drug
      penetration enhanced by lasers.

PMID- 24022681
TI  - Near-infrared light-sensitive liposomes for the enhanced photothermal tumor
      treatment by the combination with chemotherapy.
AB  - PURPOSE: To develop a near-infrared (NIR) light-sensitive liposome, which
      contains hollow gold nanospheres (HAuNS) and doxorubicin (DOX), and evaluate
      their potential utility for enhancing antitumor activity and controlling drug
      release. METHODS: The liposomes (DOX&HAuNS-TSL) were designed based on a thermal
      sensitive liposome (TSL) formulation, and hydrophobically modified HAuNS were
      attached onto the membrane of the liposomes. The behavior of DOX release from the
      liposomes was investigated by the dialysis, diffusion in agarose gel and cellular
      uptake of the drug. The biodistribution of DOX&HAuNS-TSL was assessed by i.v.
      injection in tumor-bearing nude mice. Antitumor efficacy was evaluated both
      histologically using excised tissue and intuitively by measuring the tumor size
      and weight. RESULTS: Rapid and repetitive DOX release from the liposomes
      (DOX&HAuNS-TSL), could be readily achieved upon NIR laser irradiation. The
      treatment of tumor cells with DOX&HAuNS-TSL followed by NIR laser irradiation
      showed significantly greater cytotoxicity than the treatment with DOX&HAuNS-TSL
      alone, DOX-TSL alone (chemotherapy alone) and HAuNS-TSL plus NIR laser
      irradiation (Photothermal ablation, PTA, alone). In vivo antitumor study
      indicated that the combination of simultaneous photothermal and chemotherapeutic
      effect mediated by DOX&HAuNS-TSL plus NIR laser presented a significantly higher
      antitumor efficacy than the PTA alone mediated by HAuNS-TSL plus NIR laser
      irradiation. CONCLUSIONS: Our study could be as the valuable reference and
      direction for the clinical application of PTA in tumor therapy.

PMID- 24022682
TI  - The effect of glutathione as chain transfer agent in PNIPAAm-based thermo
      responsive hydrogels for controlled release of proteins.
AB  - PURPOSE: To control degradation and protein release using thermo-responsive
      hydrogels for localized delivery of anti-angiogenic proteins. METHODS: Thermo
      responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and crosslinked
      with poly(ethylene glycol)-co-(L-lactic acid) diacrylate (Acry-PLLA-b-PEG-b-PLLA
      Acry) were synthesized via free radical polymerization in the presence of
      glutathione, a chain transfer agent (CTA) added to modulate their degradation and
      release properties. Immunoglobulin G (IgG) and the recombinant proteins
      Avastin(r) and Lucentis(r) were encapsulated in these hydrogels and their release
      was studied. RESULTS: The encapsulation efficiency of IgG was high (75-87%) and
      decreased with CTA concentration. The transition temperature of these hydrogels
      was below physiological temperature, which is important for minimally invasive
      therapies involving these materials. The toxicity from unreacted monomers and
      free radical initiators was eliminated with a minimum of three buffer
      extractions. Addition of CTA accelerated degradation and resulted in complete
      protein release. Glutathione caused the degradation products to become
      solubilized even at 37 degrees C. Hydrogels prepared without glutathione did not
      disintegrate nor released protein completely after 3 weeks at 37 degrees C.
      PEGylation of IgG postponed the burst release effect. Avastin(r) and Lucentis(r)
      released from degraded hydrogels retained their biological activity. CONCLUSIONS:
      These systems offer a promising platform for the localized delivery of proteins.

PMID- 24022683
TI  - Management of symptomatic mesenchymal hamartoma of the chest wall: surgical
      resection only in symptomatic cases.
AB  - Mesenchymal hamartoma of the chest wall (MHCW) is a rare neonatal benign tumor
      with an estimated incidence of 1 in 3 000 among primary bone tumors, and 1 in one
      million in the general population. Traditionally, the treatment of choice was an
      "en bloc" resection, but surgery limited to symptomatic cases, is now suggested
      by most authors due to the numerous cases of spontaneous regressions. We report 2
      patients of symptomatic MHCW, characterized by progressive respiratory distress,
      who underwent surgical treatment with prompt resolution of symptoms. Surgeons and
      neonatologists should be aware of this rare condition and its possible fatal or
      nearly-fatal complications.

PMID- 24022684
TI  - Indocyanine green-enhanced fluorescence optical imaging in patients with early
      and very early arthritis: a comparative study with magnetic resonance imaging.
AB  - OBJECTIVE: Indocyanine green-enhanced fluorescence optical imaging (FOI) is a
      novel diagnostic tool for the assessment of inflammation in arthritis. We
      undertook this study to compare FOI with magnetic resonance imaging (MRI) in 32
      patients with early and very early untreated arthritis (mean disease duration 7.1
      months). METHODS: FOI images were acquired with the commercially available
      Xiralite system. Image interpretation was done for an early phase (phase 1), an
      intermediate phase (phase 2), and a late phase (phase 3), and for an
      electronically generated composite image. The results were compared with those of
      clinical examination (960 joints) and contrast (gadolinium)-enhanced 1.5T MRI
      (382 joints) of the clinically more affected hand. Additionally, we evaluated FOI
      in a control group of 46 subjects without any signs of inflammatory joint disease
      (1,380 joints). RESULTS: With MRI as the reference method, the sensitivity of FOI
      was 86% and the specificity was 63%, while the composite image, phase 1, and
      phase 3 reached high specificities (87%, 90%, and 88%, respectively). The results
      differed considerably between the composite image and the phases. FOI did not
      detect inflammation in 11 joint regions that showed palmar tenosynovitis on MRI.
      Intrareader and interreader agreements were moderate to substantial (kappa = 0.55
      0.73). In the control group, FOI showed positive findings in 5% of normal joints
      in phase 2. CONCLUSION: Further multicenter studies will address the question of
      whether FOI allows sensitive and reliable detection of inflammatory changes in
      early arthritis, as suggested by our initial findings. If this is confirmed, FOI
      has the potential to be a sensitive and valuable tool for monitoring disease
      activity on site in clinical settings and for serving as an outcome parameter in
      clinical trials.

PMID- 24022685
TI  - Efficient collection of excitation energy from a linear-shaped weakly interacted
      perylenetetracarboxylic diimides array.
AB  - A series of novel light-harvesting compounds (namely PO-PN, PO-PO-PN and PO-PO-PO
      PN) were synthesized with a linear-shaped phenoxy group-substituted
      perylenetetracarboxylic diimide (PO) oligomer as donor and a pyrrolidinyl group
      substituted perylenetetracarboxylic diimide (PN) as acceptor. The photophysical
      properties of these linear-shaped compounds are investigated by steady state
      electronic absorption, fluorescence spectra and lifetime measurements. The ground
      state interactions between the neighbor PO subunits within these three compounds
      are weak. No matter which PO subunit is excited in these linear molecules, the
      excitation energy is finally collected by the PN subunit. The excitation energy
      can transfer as long as 47 A without any decrease in efficiency. The energy
      transfer rate constants determined by femtosecond transient absorption
      experiments are fast and close to that of the energy transfer from B800 to B850
      in LH II of natural photosynthesis. 

PMID- 24022686
TI  - Serotonin transporter in lymphocytes of rats exposed to physical restraint
      stress.
AB  - OBJECTIVES: Glucocorticoids and stress cause transcriptional and functional
      changes on the serotonin transporter (SERT) in the central nervous system. Stress
      can produce specific modifications of SERT in lymphocytes, which could be
      associated with alterations in immune response. The aim of this study was to
      evaluate the effect of a physical restraint stress protocol on (1) rat lymphocyte
      proliferation in the presence of the selective serotonin reuptake inhibitor
      fluoxetine and (2) SERT kinetic parameters, i.e. binding capacity (Bmax),
      affinity (Kd) and Hill coefficient (nH). METHODS: Male adult Sprague-Dawley rats
      were placed in Plexiglass boxes (5 h daily for 5 days), and blood was obtained by
      cardiac puncture on day 6. Serum corticosterone was quantitated by an
      immunoenzymatic assay. Lymphocytes were isolated by density gradients and
      adhesion to plastic, of which there was sufficient material for further
      experiments, then cultured with or without the mitogen concanavalin A (Con A, 2
      MUg/ml) and fluoxetine (1-50 MUM). Cell proliferation was measured with
      tetrazolium salts, and [(3)H]paroxetine was used as a SERT-specific ligand for
      binding assays. RESULTS: Restraint produced a significant increase in serum
      corticosterone of stressed rats. The proliferative response to Con A was similar
      in the controls and stressed animals. Fluoxetine reduced cell proliferation with
      and without Con A. Restraint diminished the inhibitory effect of fluoxetine on
      proliferation. Restraint also increased Bmax and Kd, but decreased nH. Treatment
      of rats with actinomycin D, a transcription inhibitor, reduced Bmax in stressed
      animals. CONCLUSIONS: Restraint stress modulated the effect of fluoxetine on cell
      proliferation, probably through the modification of the presence and the function
      of SERT.

PMID- 24022687
TI  - Functional diversity of genes for the biosynthesis of paeoniflorin and its
      derivatives in Paeonia.
AB  - The Paeonia root, with or without bark, are considered vital traditional Chinese
      medicine materials; the examples are those of Bai Shao, Chi Shao, and Dan Pi. In
      this study, we examine 24 genes and their expressions involved in the
      biosynthesis of paeoniflorin and its derivatives, which are active compounds of
      the Paeonia root, in Paeonia lactiflora and P. suffruticosa, as well as other
      related plants, Punica granatum, Rhus radicans, and Coriaria nepalensis. Our
      phylogenetic analyses suggest that these genes have functional diversity, and
      analysis of the transcriptional level shows paeoniflorin and gallic acid
      biosynthesis-related genes exhibit different transcription profiles in flowers,
      carpels, bark-free roots, and bark of P. lactiflora. The correlation analysis of
      gene expression and active compound contents support the idea that
      hydroxymethylglutaryl-CoA synthase and phosphomevalonate kinase in the mevalonate
      pathway and 3-dehydroquinate dehydratase/shikimate dehydrogenase in shikimate
      biosynthesis are potentially closely related to the accumulation of paeoniflorin
      and benzoylpaeoniflorin. Coupling gene diversity with chemical analysis, we show
      that paeoniflorin and its derived aromatic amino acids are predominant in bark.

PMID- 24022688
TI  - Differential polarization nonlinear optical microscopy with adaptive optics
      controlled multiplexed beams.
AB  - Differential polarization nonlinear optical microscopy has the potential to
      become an indispensable tool for structural investigations of ordered biological
      assemblies and microcrystalline aggregates. Their microscopic organization can be
      probed through fast and sensitive measurements of nonlinear optical signal
      anisotropy, which can be achieved with microscopic spatial resolution by using
      time-multiplexed pulsed laser beams with perpendicular polarization orientations
      and photon-counting detection electronics for signal demultiplexing. In addition,
      deformable membrane mirrors can be used to correct for optical aberrations in the
      microscope and simultaneously optimize beam overlap using a genetic algorithm.
      The beam overlap can be achieved with better accuracy than diffraction limited
      point-spread function, which allows to perform polarization-resolved measurements
      on the pixel-by-pixel basis. We describe a newly developed differential
      polarization microscope and present applications of the differential microscopy
      technique for structural studies of collagen and cellulose. Both, second harmonic
      generation, and fluorescence-detected nonlinear absorption anisotropy are used in
      these investigations. It is shown that the orientation and structural properties
      of the fibers in biological tissue can be deduced and that the orientation of
      fluorescent molecules (Congo Red), which label the fibers, can be determined.
      Differential polarization microscopy sidesteps common issues such as
      photobleaching and sample movement. Due to tens of megahertz alternating
      polarization of excitation pulses fast data acquisition can be conveniently
      applied to measure changes in the nonlinear signal anisotropy in dynamically
      changing in vivo structures.

PMID- 24022689
TI  - Microfluidic biosensing systems using magnetic nanoparticles.
AB  - In recent years, there has been rapidly growing interest in developing hand held,
      sensitive and cost-effective on-chip biosensing systems that directly translate
      the presence of certain bioanalytes (e.g., biomolecules, cells and viruses) into
      an electronic signal. The impressive and rapid progress in micro- and
      nanotechnology as well as in biotechnology enables the integration of a variety
      of analytical functions in a single chip. All necessary sample handling and
      analysis steps are then performed within the chip. Microfluidic systems for
      biomedical analysis usually consist of a set of units, which guarantees the
      manipulation, detection and recognition of bioanalytes in a reliable and flexible
      manner. Additionally, the use of magnetic fields for performing the
      aforementioned tasks has been steadily gaining interest. This is because magnetic
      fields can be well tuned and applied either externally or from a directly
      integrated solution in the biosensing system. In combination with these applied
      magnetic fields, magnetic nanoparticles are utilized. Some of the merits of
      magnetic nanoparticles are the possibility of manipulating them inside
      microfluidic channels by utilizing high gradient magnetic fields, their detection
      by integrated magnetic microsensors, and their flexibility due to
      functionalization by means of surface modification and specific binding. Their
      multi-functionality is what makes them ideal candidates as the active component
      in miniaturized on-chip biosensing systems. In this review, focus will be given
      to the type of biosening systems that use microfluidics in combination with
      magnetoresistive sensors and detect the presence of bioanalyte tagged with
      magnetic nanoparticles.

PMID- 24022690
TI  - Photochemistry and Cytotoxicity Evaluation of Heptamethinecyanine Near Infrared
      (NIR) Dyes.
AB  - The present study investigates the photochemical properties of potential
      photosensitizers for photodynamic therapy, namely four commercial
      heptamethinecyanine dyes (IR125, IR780, IR813, IR820). Spectroscopic studies were
      made by means of laser induced fluorescence and laser flash photolysis in order
      to obtain fluorescence quantum yields and transient absorption spectra.
      Fluorescence lifetimes were also determined. The differences encountered were
      essentially related with the interaction of the sulfonate groups with the
      solvent, and also regarding the rigidification of the central bridge connecting
      the two nitrogen-containing heterocyclic groups. Transient absorption studies
      were performed both in aerated and oxygen free samples, to conclude about the
      formation of photoisomers and triplet state. For the four dyes under study, a
      cytotoxic evaluation in the dark and after irradiation was performed using HeLa
      cells as the model cell line, which revealed significant changes after
      irradiation mainly in IR125 and IR813 dyes. Confocal microscopy analysis showed
      that these dyes tend to enter to the intracellular space. 

PMID- 24022693
TI  - Thermally reversible single-crystal to single-crystal transformation of
      mononuclear to dinuclear Zn(II) complexes by [2+2] cycloaddition reaction.
AB  - Two Zn(II) complexes of trans-4-styrylpyridine ligands undergo [2+2]
      cycloaddition reaction forming Zn(II) complex dimers in a single-crystal to
      single-crystal (SCSC) manner which were thermally reversible. The dimers are
      presumed to be the stable intermediates in the formation of 1D coordination
      polymers upon prolonged exposure to UV light.

PMID- 24022692
TI  - Expanded CD8+ T cells of murine and human CLL are driven into a senescent KLRG1+
      effector memory phenotype.
AB  - Altered numbers and functions of T cells have previously been demonstrated in
      chronic lymphocytic leukemia (CLL) patients. However, dynamics and specific T
      cell subset alterations have not been studied in great detail. Therefore, we
      studied CLL blood lymphocyte subsets of individual patients in a longitudinal
      manner. Dynamic expansions of blood CD4 + and CD8 + T-cell numbers were
      consistently associated with a progressively increasing CLL leukemic compartment.
      Interestingly, the T-cell subset expansion over time was more pronounced in CD38
      + CLL. Additionally, we performed gene expression profiling of CD3 + T cells of
      CLL patients and normal donors. Using gene set enrichment analysis, we found
      significant enrichment of genes with higher expression in CLL T cells within CD8+
      effector memory and terminal effector T-cell gene signatures. In agreement with
      these data, we observed a marked expansion of phenotypic CD8 + effector memory T
      cells in CLL by flow cytometry. Moreover, we observed that increments of CD8 +
      effector memory T cells in human CLL and also mouse CLL (EMU-TCL1 model) were due
      to an expansion of the inhibitory killer cell lectin-like receptor G1 (KLRG1)
      expressing cellular subset. Furthermore, higher plasma levels of the natural
      KLRG1 ligand E-cadherin were detected in CLL patients compared to normal donor
      controls. The predominance of KLRG1+ expression within CD8+ T cells in
      conjunction with increased systemic soluble E-cadherin might significantly
      contribute to CLL immune dysfunction and might additionally represent an
      important component of the CLL microenvironment.

PMID- 24022691
TI  - Archaeal diversity in biofilm technologies applied to treat urban and industrial
      wastewater: recent advances and future prospects.
AB  - Biological wastewater treatment (WWT) frequently relies on biofilms for the
      removal of anthropogenic contaminants. The use of inert carrier materials to
      support biofilm development is often required, although under certain operating
      conditions microorganisms yield structures called granules, dense aggregates of
      self-immobilized cells with the characteristics of biofilms maintained in
      suspension. Molecular techniques have been successfully applied in recent years
      to identify the prokaryotic communities inhabiting biofilms in WWT plants.
      Although methanogenic Archaea are widely acknowledged as key players for the
      degradation of organic matter in anaerobic bioreactors, other biotechnological
      functions fulfilled by Archaea are less explored, and research on their
      significance and potential for WWT is largely needed. In addition, the occurrence
      of biofilms in WWT plants can sometimes be a source of operational problems. This
      is the case for membrane bioreactors (MBR), an advanced technology that combines
      conventional biological treatment with membrane filtration, which is strongly
      limited by biofouling, defined as the undesirable accumulation of microbial
      biofilms and other materials on membrane surfaces. The prevalence and spatial
      distribution of archaeal communities in biofilm-based WWT as well as their role
      in biofouling are reviewed here, in order to illustrate the significance of this
      prokaryotic cellular lineage in engineered environments devoted to WWT.

PMID- 24022695
TI  - A review of our roots: blacks in gerontology.
AB  - The historical underpinnings in the field of gerontology rest on the
      contributions of scholars across a myriad of racial and ethnic backgrounds. With
      the increasing diversity of the adult population, there is a need to increase the
      number of researchers who study older adults from diverse racial and ethnic
      populations in general and Black elderly people in particular. Furthermore, it is
      important to document the participation of Black older adults in our earliest and
      continuing research efforts. Understanding the historical context and the
      foundational influence of Black scholars in this field is critical. To realize
      its humble beginnings, one must become aware of the contributions by Black
      scholars who have a vested interest in the aging process. With universal
      similarities and unique differences among older adults, there is a need to
      acknowledge the past and current scholarship of those who study the aging
      processes of Blacks while marveling over the future possibilities. The purpose of
      this review is to elucidate the legacy and current contributions, philosophies,
      and research of Black scholars in the field of gerontology. In addition,
      exploration of the theoretical and conceptual frameworks used to establish
      national and organizational initiatives is reviewed. The impetus in initiating
      and continuing this work requires a "knowledge of our roots" while moving into
      the future. It is important to learn the history and significance of Black
      scholars in gerontology, the contributions of older Blacks, and appreciate the
      resiliency and marveled life course of this unique population. 

PMID- 24022694
TI  - Feeding of ticks on animals for transmission and xenodiagnosis in Lyme disease
      research.
AB  - Transmission of the etiologic agent of Lyme disease, Borrelia burgdorferi, occurs
      by the attachment and blood feeding of Ixodes species ticks on mammalian hosts.
      In nature, this zoonotic bacterial pathogen may use a variety of reservoir hosts,
      but the white-footed mouse (Peromyscus leucopus) is the primary reservoir for
      larval and nymphal ticks in North America. Humans are incidental hosts most
      frequently infected with B. burgdorferi by the bite of ticks in the nymphal
      stage. B. burgdorferi adapts to its hosts throughout the enzootic cycle, so the
      ability to explore the functions of these spirochetes and their effects on
      mammalian hosts requires the use of tick feeding. In addition, the technique of
      xenodiagnosis (using the natural vector for detection and recovery of an
      infectious agent) has been useful in studies of cryptic infection. In order to
      obtain nymphal ticks that harbor B. burgdorferi, ticks are fed live spirochetes
      in culture through capillary tubes. Two animal models, mice and nonhuman
      primates, are most commonly used for Lyme disease studies involving tick feeding.
      We demonstrate the methods by which these ticks can be fed upon, and recovered
      from animals for either infection or xenodiagnosis. 

PMID- 24022696
TI  - [Progressive hearing impairment with deletion in GJB2 gene despite normal newborn
      hearing screening].
AB  - OBJECTIVE: Hearing impairment is the most common sensorineural disease in humans.
      About 1-3 per 1 000 neonates suffers at birth or in the first years from high
      grade to severe hearing impairment. About half of the cases are due to genetic
      alterations. Most commonly, the GJB2 gene (connexin-26) is concerned with the
      mutation c.35delG. MATERIAL AND METHODES: All patients showed a severe to
      profound hearing impairment to the course. DNA isolation, amplification and
      sequencing was performed using standard techniques. RESULTS: In the studied
      patient population we have 142 pa-tients with a homozygous deletion mutation in
      GJB2 gene (c.35delG) and 29 patients who are heterozygous for this mutation on
      one allele and heterozygous for another loss-of-function mutation in GJB2 gene.
      Of these 171 patients were 16 (9.3%) on an inconspicuous newborn hearing
      screening using Otoacoustic Emissions (OAE). Total was observed a progression of
      hearing impairment in 31 of these patients (18.1%). CONCLUSIONS: This fact
      suggests that homozygous deletion mutation c.35delG does not always contribute to
      an congenital hearing impairment, but to a progressive hearing loss that might
      develop over the first months and years of life. Additionally, we have to re
      evaluate the value of OAE for newborn hearing screening, keeping in mind that one
      positive result is no warranty for a normal development of hearing function, but
      a result that should be checked in the course. We recommend annual hearing tests
      to the paediatrician and with a known familial hearing loss and other risk
      factors pedaudiological controls.

PMID- 24022697
TI  - Ruthenium-catalyzed oxidative ortho-benzoxylation of acetanilides with aromatic
      acids.
AB  - Substituted acetanilides reacted with aromatic acids in the presence of [{RuCl2(p
      cymene)}2], AgSbF6 and (NH4)2S2O8 in ClCH2CH2Cl at 100  degrees C for 24 h
      yielding ortho-benzoxylated acetanilides in good to excellent yields in a highly
      regioselective manner via C-H bond activation. 

PMID- 24022698
TI  - Human disease: Cell types in profile.

PMID- 24022699
TI  - Molecular evolution: Rearrangements for fitness.

PMID- 24022700
TI  - Evolutionary genetics: a complex case of resource management.

PMID- 24022701
TI  - Disease genetics: Double danger from mitochondrial mutations.

PMID- 24022703
TI  - Ion transporters in brain endothelial cells that contribute to formation of brain
      interstitial fluid.
AB  - Ions and water transported across the endothelium lining the blood-brain barrier
      contribute to the fluid secreted into the brain and are important in maintaining
      appropriate volume and ionic composition of brain interstitial fluid. Changes in
      this secretion process may occur after stroke. The present study identifies at
      transcript and protein level ion transporters involved in the movement of key
      ions and examines how levels of certain of these alter following oxidative
      stress. Immunohistochemistry provides evidence for Cl-/HCO3- exchanger, AE2, and
      Na+, HCO3- cotransporters, NBCe1 and NBCn1, on brain microvessels. mRNA analysis
      by RT-PCR reveals expression of these transporters in cultured rat brain
      microvascular endothelial cells (both primary and immortalized GPNT cells) and
      also Na+/H+ exchangers, NHE1 (primary and immortalized) and NHE2 (primary cells
      only). Knock-down using siRNA in immortalized GPNT cells identifies AE2 as
      responsible for much of the Cl-/HCO3- exchange following extracellular chloride
      removal and NHE1 as the transporter that accounts for most of the Na+/H+ exchange
      following intracellular acidification. Transcript levels of both AE2 and NHE1 are
      increased following hypoxia/reoxygenation. Further work is now required to
      determine the localization of the bicarbonate transporters to luminal or
      abluminal membranes of the endothelial cells as well as to identify and localize
      additional transport mechanisms that must exist for K+ and Cl-.

PMID- 24022702
TI  - Emerging patterns of somatic mutations in cancer.
AB  - Recent advances in technological tools for massively parallel, high-throughput
      sequencing of DNA have enabled the comprehensive characterization of somatic
      mutations in a large number of tumour samples. In this Review, we describe recent
      cancer genomic studies that have assembled emerging views of the landscapes of
      somatic mutations through deep-sequencing analyses of the coding exomes and whole
      genomes in various cancer types. We discuss the comparative genomics of different
      cancers, including mutation rates and spectra, as well as the roles of
      environmental insults that influence these processes. We highlight the developing
      statistical approaches that are used to identify significantly mutated genes, and
      discuss the emerging biological and clinical insights from such analyses, as well
      as the future challenges of translating these genomic data into clinical impacts.

PMID- 24022704
TI  - Phosphoinositide substrates of myotubularin affect voltage-activated Ca2+ release
      in skeletal muscle.
AB  - Skeletal muscle excitation-contraction (E-C) coupling is altered in several
      models of phosphatidylinositol phosphate (PtdInsP) phosphatase deficiency and
      ryanodine receptor activity measured in vitro was reported to be affected by
      certain PtdInsPs, thus prompting investigation of the physiological role of
      PtdInsPs in E-C coupling. We measured intracellular Ca2+ transients in voltage
      clamped mouse muscle fibres microinjected with a solution containing a PtdInsP
      substrate (PtdIns(3,5)P2 or PtdIns(3)P) or product (PtdIns(5)P or PtdIns) of the
      myotubularin phosphatase MTM1. No significant change was observed in the presence
      of either PtdIns(5)P or PtdIns but peak SR Ca2+ release was depressed by ~30% and
      50% in fibres injected with PtdIns(3,5)P2 and PtdIns(3)P, respectively, with no
      concurrent alteration in the membrane current signals associated with the DHPR
      function as well as in the voltage dependence of Ca2+ release inactivation. In
      permeabilized muscle fibres, the frequency of spontaneous Ca2+ release events was
      depressed in the presence of the three tested phosphorylated forms of PtdInsP
      with PtdIns(3,5)P2 being the most effective, leading to an almost complete
      disappearance of Ca2+ release events. Results support the possibility that
      pathological accumulation of MTM1 substrates may acutely depress ryanodine
      receptor-mediated Ca2+ release. Overexpression of a mCherry-tagged form of MTM1
      in muscle fibres revealed a striated pattern consistent with the triadic area.
      Ca2+ release remained although unaffected by MTM1 overexpression and was also
      unaffected by the PtdIns-3-kinase inhibitor LY2940002, suggesting that the 3
      phosphorylated PtdIns lipids active on voltage-activated Ca2+ release are
      inherently maintained at a low level, inefficient on Ca2+ release in normal
      conditions.

PMID- 24022705
TI  - New perspectives of nanoneuroprotection, nanoneuropharmacology and
      nanoneurotoxicity: modulatory role of amino acid neurotransmitters, stress,
      trauma, and co-morbidity factors in nanomedicine.
AB  - Recent advancement in nanomedicine suggests that nanodrug delivery using
      nanoformulation of drugs or use of nanoparticles for neurodiagnostic and/or
      neurotherapeutic purposes results in superior effects than the conventional drugs
      or parent compounds. This indicates a bright future for nanomedicine in treating
      neurological diseases in clinics. However, the effects of nanoparticles per se in
      inducing neurotoxicology by altering amino acid neurotransmitters, if any, are
      still being largely ignored. The main aim of nanomedicine is to enhance the drug
      availability within the central nervous system (CNS) for greater therapeutic
      successes. However, once the drug together with nanoparticles enters into the CNS
      compartments, the fate of nanomaterial within the brain microenvironment is
      largely remained unknown. Thus, to achieve greater success in nanomedicine, our
      knowledge in understanding nanoneurotoxicology in detail is utmost important. In
      addition, how co-morbidity factors associated with neurological disease, e.g.,
      stress, trauma, hypertension or diabetes, may influence the neurotherapeutic
      potentials of nanomedicine are also necessary to explore the details. Recent
      research in our laboratory demonstrated that engineered nanoparticles from metals
      or titanium nanowires used for nanodrug delivery in laboratory animals markedly
      influenced the CNS functions and alter amino acid neurotransmitters in healthy
      animals. These adverse reactions of nanoparticles within the CNS are further
      aggravated in animals with different co-morbidity factors viz., stress, diabetes,
      trauma or hypertension. This effect, however, depends on the composition and dose
      of the nanomaterials used. On the other hand, nanodrug delivery by TiO2 nanowires
      enhanced the neurotherapeutic potential of the parent compounds in CNS injuries
      in healthy animals and do not alter amino acids balance. However, in animals with
      any of the above co-morbidity factors, high dose of nanodrug delivery is needed
      to achieve some neuroprotection. Taken together, it appears that while exploring
      new nanodrug formulations for neurotherapeutic purposes, co-morbidly factors and
      composition of nanoparticlesrequire more attention. Furthermore, neurotoxicity
      caused by nanoparticles per se following nanodrug delivery may be examined in
      greater detail with special regards to changes in amino acid balance in the CNS.

PMID- 24022706
TI  - Selective regulation of polyamine metabolism with methylated polyamine analogues.
AB  - Polyamine metabolism is intimately linked to the physiological state of the cell.
      Low polyamines levels promote growth cessation, while increased concentrations
      are often associated with rapid proliferation or cancer. Delicately balanced
      biosynthesis, catabolism, uptake and excretion are very important for maintaining
      the intracellular polyamine homeostasis, and deregulated polyamine metabolism is
      associated with imbalanced metabolic red/ox state. Although many cellular targets
      of polyamines have been described, the precise molecular mechanisms in these
      interactions are largely unknown. Polyamines are readily interconvertible which
      complicate studies on the functions of the individual polyamines. Thus, non
      metabolizable polyamine analogues, like carbon-methylated analogues, are needed
      to circumvent that problem. This review focuses on methylated putrescine,
      spermidine and spermine analogues in which at least one hydrogen atom attached to
      polyamine carbon backbone has been replaced by a methyl group. These analogues
      allow the regulation of both metabolic and catabolic fates of the parent
      molecule. Substituting the natural polyamines with methylated analogue(s) offers
      means to study either the functions of an individual polyamine or the effects of
      altered polyamine metabolism on cell physiology. In general, gem-dimethylated
      analogues are considered to be non-metabolizable by polyamine catabolizing
      enzymes spermidine/spermine-N1-acetyltransferase and acetylpolyamine oxidase and
      they support short-term cellular proliferation in many experimental models.
      Monomethylation renders the analogues chiral, offering some advantage over gem
      dimethylated analogues in the specific regulation of polyamine metabolism. Thus,
      methylated polyamine analogues are practical tools to meet existing biological
      challenges in solving the physiological functions of polyamines.

PMID- 24022707
TI  - Is there evidence for post-translational modification of beta cell autoantigens
      in the aetiology and pathogenesis of type 1 diabetes?
AB  - Storling and colleagues hypothesise in this issue (Diabetologia DOI:
      10.1007/s00125-013-3045-3 ) that post-translational modification (PTM) of
      autoantigens might create tissue-specific neo-epitopes that could trigger type 1
      diabetes. Data on PTM of islet autoantigens are scarce and readers should not
      believe that the PTM hypothesis is supported by strong experimental evidence. The
      proposed genetic factors are many but their possible contribution is conjectural.
      There is a lack of a rational approach to test the PTM hypothesis at the
      different stages of type 1 diabetes. Research that carefully addresses each stage
      of the type 1 diabetes disease process is warranted to advance our understanding
      of autoimmune (type 1) diabetes.

PMID- 24022708
TI  - A correlative study of polymorphisms of CYP2C19 and MDR1  C3435T with the
      pharmacokinetic profiles of lansoprazole and its  main metabolites following
      single oral administration in healthy  adult Chinese subjects.
AB  - Considering that the genotypes of CYP2C19 and MDRI C3435T are two major factors
      attributed to the inter-individual pharmacokinetic variability of lansoprazole
      (LSZ), the aim of the study was to simultaneously elucidate the effects of
      CYP2C19 and MDRI C3435T polymorphisms on the pharmacokinetics difference of LSZ
      and its metabolites 5'-hydroxy lansoprazole (HLSZ) and lansoprazole sulphone
      (LSZS) following oral administration of LSZ tablets in healthy Chinese subjects.
      Plasma concentration of LSZ, HLSZ and LSZS were quantified by a sensitive and
      specific LC-MS/MS method, while the genotypes of CYP2C19 and MDRI C3435T for each
      subject were identified by a direct sequencing method. Statistical analysis was
      performed in the pharmacokinetic parameters including Cmax, t1/2, Tmax, MRTo_-,
      AUCO-2 and AUCo_r among different genotype groups of CYP2C 19 and MDRI C3435T.
      Compared to the CYP2Cl9 EMs, the CYP2C 19 PM group showed slower elimination and
      betteroral bioavailability of LSZ, much higher plasma concentrations of LSZS and
      lower concentrations of HLSZ with statistically significance. Despite a tendency
      of more favorable absorption and rapid elimination of LSZ in wild genotype, no
      significant pharmacokinetics difference was observed between the wild genotype of
      MDR1 C3435T and its mutant types. In conclusion, the pharmacokinetics of MDRI
      C3435T.

PMID- 24022709
TI  - Pharmacokinetic interaction studies of fenugreek with CYP3A  substrates
      cyclosporine and carbamazepine.
AB  - The present study investigated the effect of fenugreek seed powder on disposition
      of CYP3A substrates, cyclosporine and carbamazepine. Rabbits were treated with
      fenugreek seed powder (300 mg/kg p.o.) for 8 days and on 8th day the single dose
      of cyclosporine (30 mg/kg, p.o.) and carbamazepine (40 mg/kg, p.o.) were
      administered to the corresponding group after 1 h of fenugreek administration.
      Blood samples were drawn at several time points and analyzed by using UPLC-MS
      (cyclosporine) and HPLC (carbamazepine). Pharmacokinetic parameters were
      calculated by using PK Solver. The present investigation reveals that there was
      no statistically significant difference between pre- and post-treated
      pharmacokinetic parameters such as AUC(o-t), AUC(o-infinity), C(max), T(max),
      T(1/2), K(el), MRT(o-infinity) , V(z/F), and Cl/F for cyclosporine and
      carbamazepine. Two tailed "P" values for all these pharmacokinetic parameters
      were more than 0.05, indicating insignificant impact of fenugreek treatment on
      the disposition of cyclosporine and carbamazepine. Further, fenugreek may also
      not have any significant effect on the functionality of P-glycoprotein as
      cyclosporine is a substrate to P-glycoprotein. The outcomes of present study
      suggested that fenugreek may not likely to interfere cyclosporine and
      carbamazepine pharmacokinetics, when co-administered with these drugs.

PMID- 24022711
TI  - Apes finding ants: Predator-prey dynamics in a chimpanzee habitat in Nigeria.
AB  - Some chimpanzee populations prey upon army ants, usually with stick tools.
      However, how their prey's subterranean nesting and nomadic lifestyle influence
      the apes' harvesting success is still poorly understood. This is particularly
      true for chimpanzees (Pan troglodytes ellioti) at Gashaka/Nigeria, which consume
      army ants (Dorylus rubellus) with much higher frequency than at other sites. We
      assessed various harvesting and search options theoretically available to the
      apes. For this, we reconstructed annual consumption patterns from feces and
      compared the physical characteristics of exploited ant nests with those that were
      not targeted. Repeated exploitation of a discovered nest is viable only in the
      short term, as disturbed colonies soon moved to a new site. Moreover, monitoring
      previously occupied nest cavities is uneconomical, as ants hardly ever re-used
      them. Thus, the apes have to detect new nests regularly, although colony density
      is relatively low (1 colony/1.3 ha). Surprisingly, visual search cues seem to be
      of limited importance because the probability of a nest being exploited was
      independent of its conspicuousness (presence of excavated soil piles, concealing
      leaf-litter or vegetation). However, chimpanzees preferentially targeted nests in
      forests or at the base of food trees, that is, where the apes spend relatively
      more time and/or where ant colony density is highest. Taken together, our
      findings suggest that, instead of employing a search strategy based on visual
      cues or spatial memory, chimpanzee predation on army ants contains a considerable
      opportunistic element.

PMID- 24022710
TI  - Prevalence of the fibromyalgia phenotype in patients with spine pain presenting
      to a tertiary care pain clinic and the potential treatment implications.
AB  - OBJECTIVE: Injections for spinal pain have high failure rates, emphasizing the
      importance of patient selection. It is possible that detecting the presence of a
      fibromyalgia (FM)-like phenotype could aid in prediction, because in these
      individuals a peripheral injection would not address pain due to alterations in
      central neurotransmission. We undertook this study to test the hypothesis that
      patients who have spine pain meeting survey criteria for FM would be
      phenotypically distinct from those who do not. METHODS: We studied 548 patients
      diagnosed as having primary spine pain. All patients completed validated self
      report questionnaires, including the Brief Pain Inventory, the PainDETECT
      questionnaire, the Hospital Anxiety and Depression Scale, measures of physical
      function, and the FM criteria and severity scales. RESULTS: Forty-two percent of
      the patients were FM positive according to the FM criteria and severity scales.
      Compared with FM-negative patients, FM-positive patients were more likely to be
      younger, unemployed, and receiving compensation for pain and to have greater pain
      severity and pain interference and more neuropathic pain descriptors as well as
      higher levels of depression and anxiety and a lower level of physical function (P
      < 0.002 for each comparison). Female sex, neuropathic pain, pain interference,
      and anxiety were independently predictive of FM status in a multivariate analysis
      (P < 0.01 for all variables). Receiver operating characteristic curve analysis
      showed a strength of association of 0.80 as measured by the cross-validated C
      statistic. CONCLUSION: Using the FM criteria and severity scales, we demonstrated
      profound phenotypic differences in a population of patients with spine pain.
      Although centralized pain cannot be confirmed with a self-report instrument
      alone, the pathophysiology of FM may help explain a portion of the variability of
      responses to spine interventions.

PMID- 24022712
TI  - Progress in chromovitrectomy: 'staining alive'.

PMID- 24022713
TI  - Chromovitrectomy and the vitreoretinal interface.
AB  - It still remains unclear to which extent the presence and the amount of retinal
      debris seen in internal limiting membrane (ILM) specimens harvested during
      macular surgery for macular holes or epiretinal membranes are related to the
      procedure of ILM peeling itself or to modifications of the surgical technique,
      such as application of vital dyes for visualization of the ILM, or to
      pathological conditions with epiretinal membrane formation at the vitreoretinal
      interface. The presence of cellular fragments on the retinal side of the removed
      ILM appears to be of multifactorial origin, and additional causes besides dye
      application need to be considered. However, morphological studies with evaluation
      of vital dyes are still of relevance and provide additional insights into the
      ultrastructure of the vitreoretinal interface and its interaction with adjuvants
      used during macular surgery. Chromovitrectomy is an emerging field in
      vitreoretinal surgery. It is of importance to better understand the tissue-dye
      interactions, which not only alter the mechanical properties of the tissue being
      stained, but may also have an impact on the functional result postoperatively.

PMID- 24022714
TI  - Material properties of the internal limiting membrane and their significance in
      chromovitrectomy.
AB  - Intraoperative visualization of the internal limiting membrane (ILM), the choice
      of a point of vantage for lifting an initial flap, the precision with which the
      ILM is grasped, adhesion between the forceps and the ILM, thickness, stiffness
      and elasticity of the ILM as well as monitoring of the completeness of ILM
      removal are all important factors for safety and efficacy of a chromovitrectomy
      intervention. The understanding of the underlying physical features of the ILM,
      such as contrast behavior and bioanatomical and biomechanical properties
      represent, thus, useful prerequisites for successful macular surgery. New
      analytical tools, such as atomic force microscopy and chromaticity analysis,
      allow new insights into ILM material characteristics, permitting a systematic
      approach to refinement of surgical technique. .

PMID- 24022715
TI  - The retinal biocompatibility of dyes in the ex vivo model of the isolated
      superfused vertebrate retina.
AB  - BACKGROUND: Peeling of the internal limiting membrane or epiretinal membranes is
      a successful principle in macular surgery to achieve a functional benefit.
      Different dyes are used to facilitate the identification of intraocular tissues.
      The aim of our work was to investigate the retinal tolerance to the different
      dyes and their solvent carriers to provide valuable data for surgeons in handling
      for an optimal intraoperative use. METHODS: Using the ex vivo model of the
      isolated superfused vertebrate retina technique, the effects of the dyes were
      tested on human and bovine retinal function. The retinas were perfused with an
      oxygen preequilibrated standard solution. The electroretinogram (ERG) was
      recorded using Ag/AgCl electrodes. After recording stable ERG amplitudes, the
      dyes brilliant blue G, indocyanine green, trypan blue, patent blue, triamcinolone
      and their solvent carriers were investigated. RESULTS: Reductions of the ERG
      amplitudes were found for each tested dye. The effects after application of the
      dyes were dependent on time and concentration of the applied dyes, which were
      different for each dye. CONCLUSION: In part, the ERG has shown strong effects
      already after a short period of dye application. Surgeons who rely on the
      intraocular use of the dyes should keep in mind our findings, and the use of some
      dyes should be limited to selected cases. The well-considered use of the dyes by
      the surgeons could lead to a better functional outcome and avoid a possible
      harmful outcome of the surgery after mishandling.

PMID- 24022716
TI  - Improved brilliant blue G staining of the internal limiting membrane with sharp
      cut filters of a novel viewing filter system.
AB  - PURPOSE: We developed a new artificial image enhancement system aimed at
      intraoperative visibility improvement as a clinical prototype. We examined each
      optical characteristic and change in intraoperative visibility using brilliant
      blue G (BBG) staining with various sharp cut filters (SCFs). METHOD: This was a
      retrospective and observational study. The system was composed of several filters
      attached to the operating microscope. Six eyes from 6 patients who presented with
      macular hole and underwent surgery using this system were studied. As a clinical
      examination, the intraoperative visibility of BBG staining intensities was
      compared for 4 kinds of SCFs during vitrectomy. Quantitative evaluation was
      calculated using the International Commission on Illumination 1976 (L*, a*, b*)
      color space (CIELAB) method. Furthermore, we evaluated each optical
      characteristic of 4 types of SCFs using extracted porcine eyes and a
      spectroradiometer as a clinical simulation. RESULTS: Suitable filter selection
      was possible for this system. The observed color tone and spectral irradiance
      changes with SCF insertion changed dynamically. In macular hole cases, the color
      intensities between BBG-stained and nonstained areas were improved using SCF-455
      and SCF-520, which was statistically significant (p < 0.05) by CIELAB.
      CONCLUSION: The system improved BBG staining intensity with the use of selective
      SCFs.

PMID- 24022717
TI  - Effect of novel vital dyes on outer blood-retina barrier function in cultured
      human retinal pigment epithelium.
AB  - PURPOSE: To assess tight junction (TJ) integrity in cultured human fetal retinal
      pigment epithelium (HFRPE) after exposure to clinically relevant novel vital
      dyes. METHODS: HFRPE floater cells were harvested from RPE primary cultures of 4
      donor eyes and seeded on polyester Transwell(r) for 4-6 weeks. The apical
      compartments of well-differentiated cultures were exposed to 0.005 mg/ml
      Coomassie violet R200 (CVR), methyl 2B (M2B) or Orange II. Periods of 30-300 s
      were chosen to mimic surgical exposure times, while 3 h was used for toxicity
      assays, with subsequent washout. Cell-cell junctions were studied by
      immunofluorescence (zonula occludens-1, ZO-1). Transepithelial electrical
      resistance (TER) was measured regarding blood-retina barrier (BRB) function.
      RESULTS: At 4-6 weeks after confluence, HFRPE had grown into pigmented hexagonal
      monolayers with stable TER values (451-1,520 Omega.cm(2)). After 300-second dye
      treatments, a continuous ZO-1 signal was detected in all vital dye-treated groups
      1.5 h after exposure, whereas trypsin controls showed patchy loss of the TJ
      stain. TER of CVR-, M2B- and Orange-II-treated groups had dropped 1.5 h after
      exposure to 148 +/- 58.4, 162 +/- 23.7 and 164 +/- 18.5 Omega.cm(2),
      respectively, compared to 73 +/- 44.9 Omega.cm(2) in positive controls. After 3 h
      of exposure to 0.005 mg/ml vital dyes in thick drops, TER maintained similar
      levels to those prior to exposure (90.8 +/- 4.7% of the original values, 93.8 +/-
      6.5 and 91.9 +/- 3.6%, respectively), together with no difference from the
      vehicle controls (94.8 +/- 6.6%). TER values recovered in all groups to prior
      levels within 3 days. CONCLUSION: Novel vital dyes (CVR, M2B and Orange II)
      caused no outer BRB function alteration.

PMID- 24022719
TI  - Dyes for EyesTM: hydrodynamics, biocompatibility and efficacy of 'heavy' (dual)
      dyes for chromovitrectomy.
AB  - As epiretinal membranes (ERMs), the internal limiting membrane (ILM) and the
      vitreous cortex are essentially transparent tissues, or translucent structures,
      nontraumatic removal may be challenging in various types of macular surgery.
      Vital dyes stain these thin tissues, thus allowing for better visualization of
      these structures during vitrectomy and selective 'membrane peeling' from the
      underlying retina. To avoid swirling of the dye within the fluid-filled vitreous
      cavity, and to better target the dye onto the macula, a fluid-air exchange is
      commonly performed. However, this may jeopardize visualization of the macula
      during peeling due to clouding of the posterior lens capsule, and may lead to
      postoperative visual field defects. Recently, a new dye solution for staining the
      ERM and ILM simultaneously has been developed that circumvents the need for fluid
      air exchange, i.e. MembraneBlue-DualTM. This paper will focus on the
      hydrodynamics and biocompatibility of this 'heavy' dual dye and its efficacy for
      staining of the ILM and/or ERMs during posterior segment surgery in a multicenter
      clinical setting.

PMID- 24022718
TI  - Effect of vital dyes on retinal pigmented epithelial cell viability and
      apoptosis: implications for chromovitrectomy.
AB  - PURPOSE: To investigate the in vitro effect of vital dyes on toxicity and
      apoptosis in a human retinal pigment epithelial cell line. METHODS: ARPE-19 cells
      were exposed to brilliant blue (BBG), Evans Blue (EB), bromophenol blue (BroB),
      indocyanine green (ICG), infracyanine green (IfCG), light green (LG), fast green
      (FG), indigo carmine (IC) and Congo red (CR). Balanced salt solution was used as
      the control. Five different concentrations and 2 exposure times were tested. Cell
      viability was determined by the MTS (1-solution methyl thiazolyl tetrazolium)
      assay and apoptosis by Bax expression on Western blot. RESULTS: All dyes
      significantly reduced cell viability after 3 min of exposure at all
      concentrations (p < 0.01), except for BBG that was safe at concentrations up to
      0.25 mg/ml and CR up to 0.05 mg/ml, while LG was safe at all concentrations.
      Toxicity was higher after 30 min of exposure. Expression of Bax was upregulated
      after all dye exposures, except BBG; ICG had the highest Bax expression (p <
      0.01). CONCLUSIONS: Overall the safest dye was BBG followed by LG, IfCG, FG, CR,
      IC, BroB, EB and ICG. ICG was toxic at all concentrations and exposure times
      tested. Moreover, BBG was the only dye that did not induce apoptosis in ARPE-19
      cells.

PMID- 24022720
TI  - Biochemical analysis and decomposition products of indocyanine green in relation
      to solvents, dye concentrations and laser exposure.
AB  - PURPOSE: To investigate pH, ions, osmolarity and precipitation of indocyanine
      green (ICG), as well as the profile of ICG decomposition products (DPs) after
      laser exposure and the interaction with quenchers. METHODS: ICG was diluted in
      water, 5% glucose (GL) or balanced salt solution (BSS) to achieve concentrations
      of 2.5, 1, 0.25 and 0.1 mg/ml. Osmolarity, pH and precipitation were analyzed
      immediately and after 24 h. Precipitation analyses were done with a scanning
      electron microscope. Anion and iodate analyses of ICG and infracyanine green
      (IfCG) were performed by capillary zone electrophoresis. With regard to DPs, 0.5
      mg/ml of ICG was assessed with high-performance liquid chromatography (HPLC)
      after 810-nm laser irradiation. DP profiles were evaluated with ICG dilution in
      quenchers (Trolox, histidine and DABCO) in 3 concentrations (0.1, 1 and 10 M).
      RESULTS: BSS promoted iso-osmotic ICG solutions of 208 mOsm (147-266) compared to
      GL with 177 mOsm. BSS solutions had a higher physiological pH of 7.2 compared
      with the GL one of 6.55. ICG precipitated more when diluted with BSS (5.95 mg);
      in contrast, GL showed less precipitate (3.6 mg). IfCG has no iodine derivates
      and other ICGs have an average 4.6% of iodate derivates. From HPLC analysis, 5
      DPs were observed. The rate of DPs was higher when BSS was used (p < 0.05). Five
      DPs have been generated with ICG, and they may be altered with the quenchers
      DABCO, histidine and Trolox. CONCLUSIONS: BSS dilution induces more precipitation
      and DPs. ICG dilution in any solvent induces DPs. Quencher use reduces the amount
      of toxic DPs.

PMID- 24022721
TI  - Staining properties of brilliant blue depending on different incubation times and
      solvents in humans.
AB  - PURPOSE: Intravitreous injection of vital dyes, e.g. brilliant blue (BBG),
      promotes better visualization of the internal limiting membrane (ILM). This paper
      investigates the staining properties of BBG depending on different incubation
      times and 2 types of solvents--5% glucose (GL) or saline solution--in a
      prospective study in patients. METHODS: This paper investigates various aspects
      of BBG in various methods. An interventional prospective study was conducted in
      patients to examine the binding properties of the blue dye diluted in either
      saline or 5% GL to epiretinal membranes (ERMs) and ILMs. Forty-nine consecutive
      patients older than 18 years scheduled for macular ERM, vitreomacular traction
      and macular hole surgeries were prospectively recruited. The primary outcomes of
      this study were the degree of ILM and ERM staining. The secondary outcomes of the
      study were the need of reinjection of BBG or any other dye, the ability of BBG to
      stain the vitreous, and frequency of complications. The staining of the ILM and
      ERM were graded as no staining, little, moderate or strong staining. RESULTS:
      There was no correlation between age (p = 0.32) or gender (p = 0.33) in the
      staining affinity of BBG to either the ILM or ERM. BBG may be an appropriate
      staining agent for the ILM in the majority (82%) of surgeries; however, in
      approximately half of the cases (45%) surgeons considered BBG not enough for ERM
      coloring and visualization. There is a tendency of BBG to stain the ILM better
      when saline solution is used compared to GL 5%; however, this was not
      statistically significant (p = 0.64). There was no difference in the staining
      efficacy of BBG to the ERMs by either solution (p = 0.70), despite the low
      staining affinity. CONCLUSION: BBG became the state-of-the-art dye for ILM
      identification. Differences in staining properties may imply that BBG should not
      be considered as first-line stain for ERM surgery. BBG is effective in ILM
      staining in over 80% of macular hole surgeries.

PMID- 24022722
TI  - A trichrome RGB endoillumination prototype system: a novel application for
      chromovitrectomy.
AB  - INTRODUCTION: LED cold light sources are utilized nowadays for endoillumination
      in vitreoretinal surgery. We investigated the effects of an individual mixing of
      red, green and blue (RGB) light from an LED illumination prototype for
      chromovitrectomy. METHODS AND TECHNIQUE: A novel RGB LED cold light illumination
      system (Dieter Mann GmbH, Mainaschaff, Germany) contains 3 RGB light sources,
      allowing for an individual mixing of light, so that the surgeon can adjust and
      control the color quality and intensity of the applied light during
      chromovitrectomy. RESULTS: Adding or subtracting the amount of any RGB light will
      consecutively change the resulting color of the light in the eye. The
      visualization of the retina or semitransparent naive structures like the vitreous
      depends on the illumination. The visualization of epiretinal membranes stained
      with vital dyes can be enhanced by an individual adjustment of the applied light.
      CONCLUSION: Selective subtraction of one RGB light unit may increase the
      visibility of delicate structures during pars plana vitrectomy.

PMID- 24022724
TI  - Initiatives promoting seamless care in medication management: an international
      review of the grey literature.
AB  - BACKGROUND: Patients' transition between hospital and community is a high-risk
      period for the occurrence of medication-related problems. AIM OF THE REVIEW: The
      objective was to review initiatives, implemented at national and regional levels
      in seven selected countries, aiming at improving continuity in medication
      management upon admission and hospital discharge. METHOD: We performed a
      structured search of grey literature, mainly through relevant websites
      (scientific, professional and governmental organizations). Regional or national
      initiatives were selected. For each initiative data on the characteristics,
      impact, success factors and barriers were extracted. National experts were asked
      to validate the initiatives identified and the data extracted. RESULTS: Most
      initiatives have been implemented since the early 2000 and are still ongoing. The
      principal actions include: development and implementation of guidelines for
      healthcare professionals, national information campaigns, education of healthcare
      professionals and development of information technologies to share data across
      settings of care. Positive results have been partially reported in terms of
      intake into practice or process measures. Critical success factors identified
      included: leadership and commitment to convey national and local forces,
      tailoring to local settings, development of a regulatory framework and
      information technology support. Barriers identified included: lack of human and
      financial resources, questions relative to responsibility and accountability,
      lack of training and lack of agreement on privacy issues. CONCLUSION: Although
      not all initiatives are applicable as such to a particular healthcare setting,
      most of them convey very interesting data that should be used when drawing
      recommendations and implementing approaches to optimize continuity of care.

PMID- 24022723
TI  - Drug prescribing in patients with renal impairment optimized by a computer-based,
      semi-automated system.
AB  - BACKGROUND: According to several studies, despite of the existence of several
      published guidelines for dosing adjustments based on renal function,
      inappropriate prescribing is a common drug-related problem in inpatient care.
      OBJECTIVE: We developed and implemented a system for drug dosage adjustment
      integrated into the Hospital computer provider order entry system. This system
      allows pharmacists to identify patients with reduced renal function, identify
      medication orders that may require dosage modifications based on renal function,
      and generate an alert with a recommendation of specific dosage adjustment. Using
      the Summary of Product Characteristics and two drug databases (Micromedex 2.0(r)
      and Lexicomp(r)), specific dosage guidelines for drugs used in patients with
      renal impairment were established. SETTING: A 264-bed tertiary teaching hospital.
      METHODS: We performed a quasi-experimental, one-group, pretest-posttest study to
      assess the efficacy of this intervention program. We compared the differences
      between the frequency of appropriate orders pre- and post-test using the McNemar
      test. MAIN OUTCOME MEASURES: the frequency of appropriate orders before the
      recommendation (pre-test) and after the recommendation (post-test). RESULTS:
      Before the intervention, the frequency of appropriate prescribing based on renal
      function was 65 %. After the intervention, this frequency was 86 % (p < 0.001).
      The interventions were more frequent in the emergency department (45 %). The
      program required 30-45 min of pharmacist time per day. The average number of
      patients reviewed daily was 28. This study found that a computer-based, semi
      automated drug-dosage program for renal failure patients was able to reduce the
      number of inappropriate orders due to renal insufficiency.

PMID- 24022725
TI  - Unlicensed and off-label use of medicines in children admitted to the intensive
      care units of a hospital in Malaysia.
AB  - BACKGROUND: Unlicensed and off-label use of medicines in paediatrics is
      widespread. However, the incidence of this practice in Malaysia has not been
      reported. OBJECTIVE: To determine the extent of unlicensed and off-label use of
      medicines in hospitalised children in the intensive care units of a tertiary care
      teaching hospital. METHODS: A prospective, observational exploratory study was
      conducted on medicines prescribed to children admitted to the 3 intensive care
      units of Universiti Kebangsaan Malaysia Medical Centre (UKMMC). RESULTS: A total
      of 194 patients were admitted to UKMMC, 168 of them received one or more drugs.
      Of 1,295 prescriptions, 353 (27.3 %) were unlicensed and 442 (34.1 %) were for
      off-label use. Forty-four percent of patients received at least one medicine for
      unlicensed use and 82.1 % received at least one medicine off-label. Preterm
      infants, children aged 28 days to 23 months, patients with hospital stays of more
      than 2 weeks, and those prescribed increasing numbers of medicines were more
      likely to receive medicines for unlicensed use. Term neonates and patients
      prescribed increasing numbers of medicines had increased risk of receiving
      medicines for off-label use. CONCLUSION: Prescribing of medicines in an
      unlicensed or off-label fashion to the children in the intensive care units of
      UKMMC was common. Further detailed studies are necessary to ensure the delivery
      of safe and effective medicines to children.

PMID- 24022728
TI  - Theoretical study on the reaction of CO2 and 2-aminobenzonitrile to form
      quinazoline-2,4(1H,3H)-dione in water without any catalyst.
AB  - Development of efficient and green routes to convert CO2 into value-added
      products is of great importance. Recently, we found that quinazoline-2,4(1H,3H)
      diones and their derivatives could be synthesized from CO2 and 2
      aminobenzonitriles in water efficiently without a catalyst and excellent yields
      were obtained, while the reactions did not occur in organic solvents. In this
      work, using density functional theory (DFT) we conduct the first theoretical work
      to study the mechanism of the reactions in water. It is revealed that CO2 reacts
      via carbonic acid (H2CO3) with 2-aminobenzonitrile to form the product. Formation
      of H2CO3 from CO2 and water is the key for the reactions to proceed smoothly in
      water without a catalyst because of two reasons. First, H2CO3 reacts with 2
      aminobenzonitriles more easily than CO2 itself; second, H2CO3 can effectively
      promote the reaction by the synergistic action of its carbonyl O atom and one of
      the hydroxyl O atoms. 

PMID- 24022727
TI  - KRAS testing in metastatic colorectal carcinoma: challenges, controversies,
      breakthroughs and beyond.
AB  - Metastatic colorectal cancer harbouring a mutation in codon 12 or 13 of the KRAS
      gene does not benefit from therapy with antibodies targeting the epidermal growth
      factor receptor (EGFR). The implementation of community KRAS testing is
      generating a rapid flow of new data that have implications for the pathologist
      and testing guidelines besides the physician. Therefore, it seems timely to draw
      together the threads of this large body of information in order that pathologists
      can be knowledgeable partners in the multidisciplinary process of targeted cancer
      therapy and to help refine current testing guidelines. This review addresses (1)
      the most relevant methodological and technical aspects of KRAS testing in terms
      of sample site (primary/metastatic), test specimens (resection/biopsy/cytology)
      and the diverse molecular methods available; (2) the issues related to daily
      practice, namely, the timing of the test, its turnaround time and the quality
      control procedures; and (3) the evidence related to the relationship between KRAS
      genetic intratumoural heterogeneity, clinical sensitivity of mutational detection
      tools and anti-EGFR treatment outcome. Hopefully, in the near future, elucidation
      of the potential of biomarker panels and of the mechanisms underlying primary and
      acquired resistance to anti-EGFR therapy will refine even further personalised
      treatment regimens for patients with metastatic colorectal cancer. 

PMID- 24022729
TI  - Brief Report: Antibodies Reacting to Brain Tissue in Basque Spanish Children with
      Autism Spectrum Disorder and Their Mothers.
AB  - Previous investigations found that a subset of children with autism spectrum
      disorder (ASD) in California possessed plasma autoantibodies that reacted
      intensely with brain interneurons or other neural profiles. Moreover, for several
      cohorts of American women, maternal autoantibody reactivity to specific fetal
      brain proteins was highly specific to mothers of children with ASD. We sought to
      determine whether children and their mothers from a regionally specific cohort
      from the Basque Country of Spain demonstrated similar reactivity. Some children's
      plasma reacted to interneurons, beaded axons or other neural profiles with no
      difference in the occurrence of these antibodies in children with or without ASD.
      Findings on the maternal antibodies confirmed previous research; plasma
      reactivity to fetal brain a combination of proteins at 37 and 73 kDa or 39 and 73
      kDa was found exclusively in mothers of children with ASD.

PMID- 24022730
TI  - Characterization and prediction of early reading abilities in children on the
      autism spectrum.
AB  - Many children with autism spectrum disorder (ASD) have reading profiles
      characterized by higher decoding skills and lower reading comprehension. This
      study assessed whether this profile was apparent in young children with ASD and
      examined concurrent and longitudinal predictors of early reading. A discrepant
      profile of reading (higher alphabet and lower meaning) was found in 62% of this
      sample. Concurrent analyses revealed that reading proficiency was associated with
      higher nonverbal cognition and expressive language, and that social ability was
      negatively related to alphabet knowledge. Nonverbal cognition and expressive
      language at mean age 21/2 years predicted later reading performance at mean age
      51/2 years. These results support the importance of early language skills as a
      foundation for reading in children with ASD.

PMID- 24022732
TI  - Discovery and evaluation of thiazinoquinones as anti-protozoal agents.
AB  - Pure compound screening has identified the dioxothiazino-quinoline-quinone
      ascidian metabolite ascidiathiazone A (2) to be a moderate growth inhibitor of
      Trypanosoma brucei rhodesiense (IC50 3.1 MUM) and Plasmodium falciparum (K1 dual
      drug resistant strain) (IC50 3.3 MUM) while exhibiting low levels of cytotoxicity
      (L6, IC50 167 MUM). A series of C-7 amide and Delta2(3) analogues were prepared
      that explored the influence of lipophilicity and oxidation state on observed anti
      protozoal activity and selectivity. Little variation in anti-malarial potency was
      observed (IC50 0.62-6.5 MUM), and no correlation was apparent between anti
      malarial and anti-T. brucei activity. Phenethylamide 7e and Delta2(3)-glycine
      analogue 8k exhibited similar anti-Pf activity to 2 but with slightly enhanced
      selectivity (SI 72 and 93, respectively), while Delta2(3)-phenethylamide 8e (IC50
      0.67 MUM, SI 78) exhibited improved potency and selectivity towards T. brucei
      rhodesiense compared to the natural product hit. A second series of analogues
      were prepared that replaced the quinoline ring of 2 with benzofuran or
      benzothiophene moieties. While esters 10a/10b and 15 were once again found to
      exhibit cytotoxicity, carboxylic acid analogues exhibited potent anti-Pf activity
      (IC50 0.34-0.035 MUM) combined with excellent selectivity (SI 560-4000). In vivo
      evaluation of a furan carboxylic acid analogue against P. berghei was undertaken,
      demonstrating 85.7% and 47% reductions in parasitaemia with ip or oral dosing
      respectively.

PMID- 24022733
TI  - Reply to the Letter to the editor: Does vitamin D improve osteoarthritis of the
      knee: a randomized controlled pilot trial.

PMID- 24022734
TI  - The lived experience of mothers of multiple children with intellectual
      disabilities.
AB  - In this study, we explored the lived experience of Japanese mothers who have
      delivered multiple children with intellectual disabilities (ID), using
      interpretative phenomenological analysis. We identified three superordinate
      themes and seven subordinate themes from the narrative data collected from 10
      participants. The superordinate themes were: abandoned hope for having an
      ordinary family, accumulating physical and mental fatigue, and searching for
      positive experiences in parenting multiple children with disabilities. How they
      perceived the birth of children with disabilities for the second time differed
      depending on the disability types; specifically, whether they detected the
      disabilities early or not. Encountering the disability in another child
      overwhelmed mothers, especially when the disabilities were diagnosed after
      several years with or without suspicion; they struggled to accept the fact.
      Despite mothers facing extreme difficulties in parenting multiple children with
      disabilities, they tried to alter the negative perceptions and find an optimistic
      way of living. 

PMID- 24022731
TI  - Plastids of marine phytoplankton produce bioactive pigments and lipids.
AB  - Phytoplankton is acknowledged to be a very diverse source of bioactive molecules.
      These compounds play physiological roles that allow cells to deal with changes of
      the environmental constrains. For example, the diversity of light harvesting
      pigments allows efficient photosynthesis at different depths in the seawater
      column. Identically, lipid composition of cell membranes can vary according to
      environmental factors. This, together with the heterogenous evolutionary origin
      of taxa, makes the chemical diversity of phytoplankton compounds much larger than
      in terrestrial plants. This contribution is dedicated to pigments and lipids
      synthesized within or from plastids/photosynthetic membranes. It starts with a
      short review of cyanobacteria and microalgae phylogeny. Then the bioactivity of
      pigments and lipids (anti-oxidant, anti-inflammatory, anti-mutagenic, anti
      cancer, anti-obesity, anti-allergic activities, and cardio- neuro-, hepato- and
      photoprotective effects), alone or in combination, is detailed. To increase the
      cellular production of bioactive compounds, specific culture conditions may be
      applied (e.g., high light intensity, nitrogen starvation). Regardless of the
      progress made in blue biotechnologies, the production of bioactive compounds is
      still limited. However, some examples of large scale production are given, and
      perspectives are suggested in the final section. 

PMID- 24022735
TI  - How mothers talk about placement of their child with autism outside the home.
AB  - In this article I use insights offered by the poststructural shift and linguistic
      turn in social scientific inquiry, specifically discourse analysis, to explore
      mothers' talk about the placement of their child with autism outside of the home.
      By viewing mothers' talk as data, I bring to light the discourses and
      interpretive practices that mothers drew on to organize their talk of placement.
      In doing so, I provide insights into how mothers gave meaning to processes of
      placement while also expanding on commonsensical discursive notions of "good"
      mothering, caregiving, and family. Implications of the findings are discussed. 

PMID- 24022736
TI  - Remodelling of femoral head-neck junction in slipped capital femoral epiphysis: a
      multicentre study.
AB  - PURPOSE: We examined the remodelling of the femoral head-neck junction in
      patients with slipped capital femoral epiphysis (SCFE) and the frequency of
      residual cam deformities. METHODS: We reviewed 69 hips in 56 patients with stable
      SCFE who had undergone in situ pinning. Mean age at slip was 11.7 years and the
      follow-up period 63.4 months. Cam deformity was evaluated using the anterior
      offset alpha (alpha) angle and head-neck offset ratio (HNOR). RESULTS: The
      average alpha angle and HNOR significantly improved from 76.2 degrees  to 51.3
      degrees  and 0.086 to 0.135, respectively; 25 hips (36.2%) still had an alpha
      angle greater than 50 degrees , and 32 hips (46.4%) had an HNOR of under 0.145. A
      multivariate analysis selected age at onset and slip angle as risk factors for
      cam deformity, with cutoff values 11.1 years and 21.0 degrees , respectively.
      CONCLUSIONS: Although most hips had remodelling of the head-neck junction, 29.4 %
      had residual cam deformities that may be susceptible to femoroacetabular
      impingement.

PMID- 24022737
TI  - Treatment of osteochondral fractures of the knee: a meta-analysis of available
      scientific evidence.
AB  - PURPOSE: Although traumatic osteochondral fractures of the knee represent a
      common pathology of the knee joint, there is no general agreement concerning
      specific treatment of this entity. This meta-analysis was initiated in order to
      evaluate scientific evidence on different treatment options for acute
      osteochondral fractures of the knee. METHODS: For this purpose an OVID-based
      systematic literature search was performed including the following databases:
      MEDLINE, MEDLINE preprints, Embase, CINAHL, Life Science Citations, British
      National Library of Health and Cochrane Central Register of Controlled Trials.
      The literature search period was from 1946 to January 2012, which led to the
      identification of 1,226 articles. After applying study-specific inclusion
      criteria a total of 19 studies with clinical follow-up of 638 patients were
      included. The methodology of these studies was systematically analysed by means
      of the Coleman Methodology Score. Outcome and success rates were evaluated
      depending on treatment applied. RESULTS: All studies (n = 19) identified
      represent case series (evidence-based medicine level IV) and included a total of
      638 patients. The average post-operative follow-up was 46 +/- 27 months (range
      3.75-108). The mean number of study subjects per study was 33 +/- 44 patients
      (range 4-169). The average Coleman Methodology Score was 29 +/- 17 points (range
      5-72). Six different scoring systems were used for clinical assessment. The
      overall clinical success rate was 83% and varied between 45 and 100%.
      CONCLUSIONS: This meta-analysis reveals a significant lack of scientific evidence
      for treatment of osteochondral fractures of the knee. No valid conclusion can be
      drawn from this study concerning the recommendation of a specific treatment
      algorithm. Nevertheless, the overall failure rate of 17% underlines that an acute
      osteochondral fracture of the knee represents an important pathology which is not
      a self-limiting injury and needs further investigation.

PMID- 24022738
TI  - Does obesity and nicotine abuse influence the outcome and complication rate after
      open-wedge high tibial osteotomy? A retrospective evaluation of five hundred and
      thirty three patients.
AB  - PURPOSE: Nicotine abuse and obesity are well-known factors leading to common post
      operative complications. However, their influence on the outcome after high
      tibial osteotomy is controversial. Thus, the aim of this study was to evaluate
      their effect on the clinical outcome with particular regard to bone non-union and
      local complications. METHODS: The functional outcome after open-wedge high tibial
      osteotomy using the TomoFix(r) plate was assessed by means of the 12-item Oxford
      knee score in a multicentre study. In addition the intra- and post-operative
      complications were determined. RESULTS: Of 533 eligible patients, 386 were
      interviewed after a mean follow-up of 3.6 years. The median Oxford knee score was
      43 points (max. 48 points). Six per cent of these patients experienced at least
      one local post-operative complication. Patients with a body mass index (BMI) of
      up to 25 and between 25 and 30 had a higher mean score by 3.5 and 1.8 points,
      respectively, compared with those having a BMI of more than 30 showing a score of
      37.5. No correlation was observed between smoking and the functional outcome.
      Smoking habits, BMI, the absolute patient weight and the interaction term between
      smoking and BMI were not significant with reference to the complication rate.
      CONCLUSIONS: This study reveals favourable mid-term results after high tibial
      osteotomy in varus osteoarthritis even in patients who smoked and obese patients.
      The indication in patients with a BMI above 30 should be handled with care due to
      the slightly inferior outcome, although the complication rate was not increased
      in these patients.

PMID- 24022739
TI  - A guided materials screening approach for developing quantitative sol-gel derived
      protein microarrays.
AB  - Microarrays have found use in the development of high-throughput assays for new
      materials and discovery of small-molecule drug leads. Herein we describe a guided
      material screening approach to identify sol-gel based materials that are suitable
      for producing three-dimensional protein microarrays. The approach first
      identifies materials that can be printed as microarrays, narrows down the number
      of materials by identifying those that are compatible with a given enzyme assay,
      and then hones in on optimal materials based on retention of maximum enzyme
      activity. This approach is applied to develop microarrays suitable for two
      different enzyme assays, one using acetylcholinesterase and the other using a set
      of four key kinases involved in cancer. In each case, it was possible to produce
      microarrays that could be used for quantitative small-molecule screening assays
      and production of dose-dependent inhibitor response curves. Importantly, the
      ability to screen many materials produced information on the types of materials
      that best suited both microarray production and retention of enzyme activity. The
      materials data provide insight into basic material requirements necessary for
      tailoring optimal, high-density sol-gel derived microarrays. 

PMID- 24022740
TI  - A densely decorated disubstituted ferrocene as an ion-pair recognition receptor.
AB  - A functionalized 1,1'-disubstituted ferrocene acts as an electro-optical ion-pair
      receptor for Mg(2+), Ca(2+), Cd(2+), and Zn(2+) cations in the presence of a co
      bound H2PO4(-) anion, through perturbation of the redox potential of the
      ferrocene unit, enhancement of the fluorescence and a noticeable colour change. 

PMID- 24022742
TI  - Na+/K+ switch of enantioselectivity in G-quadruplex DNA-based catalysis.
AB  - Here we found that the enantioselectivity of G-quadruplex DNA-based Diels-Alder
      reaction can be switched by just changing Na(+) to K(+), which is ascribed to the
      structural transformation of the G-quadruplex from antiparallel to hybrid-type.
      By tuning the ratio of Na(+)/K(+), the enantioselectivity of the Diels-Alder
      reaction could be switchable and shows much more sensitive to K(+) than to Na(+).

PMID- 24022743
TI  - Prevalence of paternal perinatal depressiveness and its link to partnership
      satisfaction and birth concerns.
AB  - Depressive disorders have shown an increasing prevalence over the past decades.
      Growing evidence suggests that pregnancy and childbirth trigger depressive
      symptoms not only in women but likewise in men. This study estimates the
      prevalence of paternal perinatal depressiveness in a German community sample and
      explores its link to partnership satisfaction as well as birth-related concerns
      and concerns about the future. Data was gathered in a longitudinal study over the
      second and third trimester of their partner's pregnancy up to 6 weeks postpartum.
      In a two-stage screening procedure, 102 expectant fathers were assessed for
      symptoms of depression, anxiety, and partnership satisfaction using the Edinburgh
      Postnatal depression Scale (EPDS), the State/Trait Anxiety Inventory, a self
      constructed questionnaire for birth concerns and the Questionnaire of
      Partnership. The prevalence of elevated depressive symptoms among expectant
      fathers was 9.8 % prenatally and 7.8 % postnatally. Prenatal relationship
      quality, prenatal EPDS scores, and birth concerns were significantly associated
      with and explained 47 % of the variance in paternal postnatal depressive
      symptoms. The prevalence of paternal depressive symptoms is a significant
      concern. Our findings point out the need for implementing awareness and screening
      for depressiveness in fathers in clinical routine in Germany as well as the
      necessity of developing a screening instrument for paternal birth-related
      anxiety.

PMID- 24022745
TI  - Synthesis, molecular structure, computational study and in vitro anticancer
      activity of dinuclear thiolato-bridged pentamethylcyclopentadienyl Rh(III) and
      Ir(III) complexes.
AB  - Neutral dinuclear dithiolato-bridged pentamethylcyclopentadienyl Rh(III)
      complexes of the type (C5Me5)2Rh2(MU-SR)2Cl2 (R = CH2Ph, 1; R = CH2CH2Ph, 2) and
      cationic dinuclear trithiolato-bridged pentamethylcyclopentadienyl Rh(III) and
      Ir(III) complexes of the type [(C5Me5)2M2(MU-SR)3](+) (M = Rh, R = CH2Ph, 3; M =
      Rh, R = CH2CH2Ph, 5; M = Rh, R = CH2C6H4-p-(t)Bu, 7: M = Ir, R = CH2Ph, 4; M =
      Ir, R = CH2CH2Ph, 6; M = Ir, R = CH2C6H4-p-(t)Bu, 8) have been synthesized from
      the chloro-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) dimers
      (C5Me5)2M2(MU-Cl)2Cl2 by reaction with the corresponding thiol derivative (RSH).
      Complexes 3-8 were isolated as chloride salts. All complexes were obtained in
      good yield and were fully characterized by spectroscopic methods. The molecular
      structures of the neutral complexes (1 and 2) show interesting features: the two
      rhodium atoms are bridged by two thiolato ligands with no metal-metal bonds and
      the pentamethylcyclopentadienyl and chlorido ligands are oriented syn to each
      other, an uncommon conformation for such dinuclear complexes. These structural
      features were rationalized using DFT calculations. Additionally, the
      antiproliferative activity of the complexes was evaluated against the cancerous
      A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) human ovarian
      cell lines and on the noncancerous HEK293 human embryonic kidney cells. All
      complexes were found to be active and the cationic iridium complexes , and are
      particularly cytotoxic, with IC50 values in the nanomolar range (IC50 < 0.1 MUM).
      The catalytic activity of the complexes for the oxidation of glutathione (GSH) to
      GSSG was evaluated by NMR spectroscopy.

PMID- 24022744
TI  - Pepper osmotin-like protein 1 (CaOSM1) is an essential component for defense
      response, cell death, and oxidative burst in plants.
AB  - Osmotin or osmotin-like protein, a PR-5 family member, is differentially induced
      in plants by abiotic and biotic stresses. Here, we demonstrate that the pepper
      (Capsicum annuum) osmotin-like protein 1 gene, CaOSM1, was required for the
      defense and hypersensitive cell death response and oxidative burst signaling
      during Xanthomonas campestris pv. vesicatoria (Xcv) infection. CaOSM1 protein was
      localized to the plasma membrane in leaf cells of Nicotiana benthamiana.
      Agrobacterium-mediated transient expression of CaOSM1 in pepper distinctly
      induced the hypersensitive cell death response and H2O2 accumulation. Knock-down
      of CaOSM1 in pepper by virus-induced gene silencing increased the susceptibility
      to Xcv infection, which was accompanied by attenuation of the cell death response
      and decreased accumulation of H2O2. CaOSM1 overexpression in transgenic
      Arabidopsis conferred reduced susceptibility and accelerated cell death response
      and H2O2 accumulation to infection by Pseudomonas syringe pv. tomato and
      Hyaloperonospora arabidopsidis. Together, these results suggest that CaOSM1 is
      involved in cell death and oxidative burst responses during plant defense against
      microbial pathogens.

PMID- 24022746
TI  - Induction of apoptosis in human myeloid leukemia cells by remote exposure of
      resistive barrier cold plasma.
AB  - Cold atmospheric plasma (CAP), an ambient temperature ionized gas, is gaining
      extensive interest as a promising addition to anti-tumor therapy primarily due to
      the ability to generate and control delivery of electrons, ions, excited
      molecules, UV photons, and reactive species such as reactive oxygen species (ROS)
      and reactive nitrogen species (RNS) to a specific site. The heterogeneous
      composition of CAP offers the opportunity to mediate several signaling pathways
      that regulate tumor cells. Consequently, the array of CAP generated products has
      limited the identification of the mechanisms of action on tumor cells. The aim of
      this work is to assess the cell death response of human myeloid leukemia cells by
      remote exposure to CAP generated RNS by utilizing a novel resistive barrier
      discharge system that primarily produces RNS. The effect of variable treatments
      of CAP generated RNS was tested in THP-1 cell (human monocytic leukemia cell
      line), a model for hematological malignancy. The number of viable cells was
      evaluated with erythrosine-B staining, while apoptosis and necrosis was assessed
      by endonuclease cleavage observed by agarose gel electrophoresis and detection of
      cells with the exclusionary dye propidium iodide and fluorescently labeled
      annexin-V by flow cytometry and fluorescent microscopy. Our observations indicate
      that treatment dosage levels of 45 s of exposure to CAP emitted RNS-induced
      apoptotic cell death and for higher dosage conditions of >=50 s of exposure to
      CAP induced necrosis. Overall the results suggest that CAP emitted RNS play a
      significant role in the anti-tumor potential of CAP.

PMID- 24022747
TI  - M-ficolin levels reflect disease activity and predict remission in early
      rheumatoid arthritis.
AB  - OBJECTIVE: To assess plasma M-ficolin concentrations in disease-modifying
      antirheumatic drug (DMARD)-naive patients with early rheumatoid arthritis (RA),
      to investigate the correlation of M-ficolin concentrations with disease activity
      markers, and to determine the predictive value of M-ficolin with respect to the
      Disease Activity Score in 28 joints (DAS28). METHODS: The study group included
      180 DMARD-naive patients with early RA who participated in a randomized
      controlled trial of methotrexate and intraarticular glucocorticoids plus either
      adalimumab or placebo/adalimumab. One hundred healthy control subjects and 51
      patients with chronic RA were also assessed. A sandwich-type time-resolved
      fluorometric immunoassay was used for quantification of plasma M-ficolin.
      RESULTS: At baseline, M-ficolin levels were highest in the group of DMARD-naive
      patients with newly diagnosed active RA, and the level in these patients
      decreased 26% after 1 year of aggressive treatment. The baseline M-ficolin level
      correlated with 5 of 7 disease activity markers, including the DAS28 and the
      Health Assessment Questionnaire (HAQ), and a similar pattern of correlations was
      observed at 1 year. Multiple logistic regression analysis showed that an elevated
      M-ficolin level at baseline was the strongest predictor of not achieving either
      DAS28 remission (odds ratio [OR] 4.18, 95% confidence interval [95% CI] 2.02
      8.63) or low disease activity (OR 2.45, 95% CI 1.13-5.28) at 1 year. The presence
      of a baseline M-ficolin level in the lowest quartile resulted in sensitivity of
      29%, specificity of 93%, and positive predictive value of 95% for low disease
      activity at 1 year. CONCLUSION: In patients with early RA, elevated plasma M
      ficolin levels correlated with a high DAS28 and a high HAQ score at baseline and
      1 year. A low M-ficolin level was the strongest predictor of remission and low
      disease activity in a multivariate analysis.

PMID- 24022748
TI  - A Bayesian adaptive dose selection procedure with an overdispersed count
      endpoint.
AB  - Adaptive trial designs can considerably improve upon traditional designs, by
      modifying design aspects of the ongoing trial, like early stopping, adding, or
      dropping doses, or changing the sample size. In the present work, we propose a
      two-stage Bayesian adaptive design for a Phase IIb study aimed at selecting the
      lowest effective dose for Phase III. In this setting, efficacy has been proved
      for a high dose in a Phase IIa proof-of-concept study, but the existence of a
      lower but still effective dose is investigated before the scheduled Phase III
      starts. In the first stage, we randomize patients to placebo, maximal tolerated
      dose, and one or more additional doses within the dose range. Based on an interim
      analysis, we either stop the study for futility or success or continue the study
      to the second stage, where newly recruited patients are allocated to placebo,
      some fairly high dose, and one additional dose chosen based on interim data. At
      the interim analysis, we use the criteria based on the predictive probability of
      success to decide on whether to stop or to continue the trial and, in the latter
      case, which dose to select for the second stage. Finally, we will select a dose
      as lowest effective dose for Phase III either at the end of the first stage or at
      the end of the second stage. We evaluate the operating characteristics of the
      procedure via simulations and present the results for several scenarios,
      comparing the performance of the proposed procedure to those of the non-adaptive
      design.

PMID- 24022749
TI  - Comprehensive transcriptional profiling of NaHCO3-stressed Tamarix hispida roots
      reveals networks of responsive genes.
AB  - Root tissue is the primary site of perception for stress from soil, and is the
      main tissue involved in stress response. Tamarix hispida is a woody halophyte
      that is highly tolerant to salt and drought stress, but little information
      available about gene expression in roots in response to abiotic stress. In this
      study, eight transcriptomes from roots of T. hispida treated with NaHCO3 for 0,
      12, 24 and 48 h (two biological replicates were set at each time point) were
      built. In total, 47,324 unigenes were generated, and 6,267 differentially
      expressed genes (DEGs) were identified. There were 2,510, 3,690, and 2,636 genes
      significantly differentially expressed after stress for 12, 24 and 48 h,
      respectively. Co-expressed DEGs were clustered into ten classes (P < 0.001). Gene
      ontology enrichment analysis showed that 13 pathways were highly enriched, such
      as signal transduction, cell wall, phosphatase activity, and lipid kinase
      activity, suggesting that these pathways play important roles in the saline
      alkaline response. Furthermore, the genes involved in lignin metabolic processes
      and biosynthesis of proline and trehalose are found closely involved in NaHCO3
      stress response. This systematic analysis may provide an in-depth view of stress
      tolerance mechanisms in T. hispida.

PMID- 24022750
TI  - Genomic prediction in maize breeding populations with genotyping-by-sequencing.
AB  - Genotyping-by-sequencing (GBS) technologies have proven capacity for delivering
      large numbers of marker genotypes with potentially less ascertainment bias than
      standard single nucleotide polymorphism (SNP) arrays. Therefore, GBS has become
      an attractive alternative technology for genomic selection. However, the use of
      GBS data poses important challenges, and the accuracy of genomic prediction using
      GBS is currently undergoing investigation in several crops, including maize,
      wheat, and cassava. The main objective of this study was to evaluate various
      methods for incorporating GBS information and compare them with pedigree models
      for predicting genetic values of lines from two maize populations evaluated for
      different traits measured in different environments (experiments 1 and 2). Given
      that GBS data come with a large percentage of uncalled genotypes, we evaluated
      methods using nonimputed, imputed, and GBS-inferred haplotypes of different
      lengths (short or long). GBS and pedigree data were incorporated into statistical
      models using either the genomic best linear unbiased predictors (GBLUP) or the
      reproducing kernel Hilbert spaces (RKHS) regressions, and prediction accuracy was
      quantified using cross-validation methods. The following results were found:
      relative to pedigree or marker-only models, there were consistent gains in
      prediction accuracy by combining pedigree and GBS data; there was increased
      predictive ability when using imputed or nonimputed GBS data over inferred
      haplotype in experiment 1, or nonimputed GBS and information-based imputed short
      and long haplotypes, as compared to the other methods in experiment 2; the level
      of prediction accuracy achieved using GBS data in experiment 2 is comparable to
      those reported by previous authors who analyzed this data set using SNP arrays;
      and GBLUP and RKHS models with pedigree with nonimputed and imputed GBS data
      provided the best prediction correlations for the three traits in experiment 1,
      whereas for experiment 2 RKHS provided slightly better prediction than GBLUP for
      drought-stressed environments, and both models provided similar predictions in
      well-watered environments. 

PMID- 24022751
TI  - A DNA sequence element that advances replication origin activation time in
      Saccharomyces cerevisiae.
AB  - Eukaryotic origins of DNA replication undergo activation at various times in S
      phase, allowing the genome to be duplicated in a temporally staggered fashion. In
      the budding yeast Saccharomyces cerevisiae, the activation times of individual
      origins are not intrinsic to those origins but are instead governed by
      surrounding sequences. Currently, there are two examples of DNA sequences that
      are known to advance origin activation time, centromeres and forkhead
      transcription factor binding sites. By combining deletion and linker scanning
      mutational analysis with two-dimensional gel electrophoresis to measure fork
      direction in the context of a two-origin plasmid, we have identified and
      characterized a 19- to 23-bp and a larger 584-bp DNA sequence that are capable of
      advancing origin activation time. 

PMID- 24022752
TI  - Posttraumatic stress disorder and symptoms among American Indians and Alaska
      Natives: a review of the literature.
AB  - PURPOSE: American Indians and Alaska Natives (AI/ANs) experience high rates of
      trauma and posttraumatic stress disorder (PTSD). We reviewed existing literature
      to address three interrelated questions: (1) What is the prevalence of PTSD and
      PTSD symptoms among AI/ANs? (2) What are the inciting events, risk factors, and
      co-morbidities in AI/ANs, and do they differ from those in the general U.S.
      population? (3) Are studies available to inform clinicians about the course and
      treatment of PTSD in this population? METHODS: We searched the PubMed and Web of
      Science databases and a database on AI/AN health, capturing an initial sample of
      77 original English-language articles published 1992-2010. After applying
      exclusion criteria, we retained 37 articles on prevalence of PTSD and related
      symptoms among AI/AN adults. We abstracted key information and organized it in
      tabular format. RESULTS: AI/ANs experience a substantially greater burden of PTSD
      and related symptoms than U.S. Whites. Combat experience and interpersonal
      violence were consistently cited as leading causes of PTSD and related symptoms.
      PTSD was associated with bodily pain, lung disorders, general health problems,
      substance abuse, and pathological gambling. In general, inciting events, risk
      factors, and co-morbidities appear similar to those in the general U.S.
      population. CONCLUSIONS: Substantial research indicates a strikingly high
      incidence of PTSD in AI/AN populations. However, inciting events, risk factors,
      and co-morbidities in AI/ANs, and how they may differ from those in the general
      population, are poorly understood. Very few studies are available on the clinical
      course and treatment of PTSD in this vulnerable population.

PMID- 24022753
TI  - Determinants of the development of post-traumatic stress disorder, in the general
      population.
AB  - PURPOSE: To assess (1) the lifetime prevalence of exposure both to trauma and
      post-traumatic stress disorder (PTSD); (2) the risk of PTSD by type of trauma;
      and (3) the determinants of the development of PTSD in the community. METHODS:
      The Diagnostic Interview for Genetic Studies was administered to a random sample
      of an urban area (N = 3,691). RESULTS: (1) The lifetime prevalence estimates of
      exposure to trauma and PTSD were 21.0 and 5.0%; respectively, with a twice as
      high prevalence of PTSD in women compared to men despite a similar likelihood of
      exposure in the two sexes; (2) Sexual abuse was the trauma involving the highest
      risk of PTSD; (3) The risk of PTSD was most strongly associated with sexual abuse
      followed by preexisting bipolar disorder, alcohol dependence, antisocial
      personality, childhood separation anxiety disorder, being victim of crime,
      witnessing violence, Neuroticism and Problem-focused coping strategies. After
      adjustment for these characteristics, female sex was no longer found to be
      significantly associated with the risk of PTSD. CONCLUSIONS: The risk for the
      development of PTSD after exposure to traumatic events is associated with several
      factors including the type of exposure, preexisting psychopathology, personality
      features and coping strategies which independently contribute to the
      vulnerability to PTSD.

PMID- 24022754
TI  - Money matters: does the reimbursement policy for second generation antipsychotics
      influence the number of recorded schizophrenia patients and the burden of
      stigmatization?
AB  - PURPOSE: In Poland, non-compliance with the reimbursement policy for second
      generation antipsychotics (SGA) manifested in prescribing SGA for patients with
      psychotic disorders other than schizophrenia may result in serious financial
      penalties. In this study, we aimed at investigating whether the implementation of
      the reimbursement policy for SGA contributed to increasing the number of patients
      with a diagnosis of schizophrenia relatively to the number of patients with a
      diagnosis of other psychotic disorders in outpatient clinics. METHODS: We
      analyzed data from Yearbooks of Mental Health that were published by the
      Institute of Psychiatry and Neurology, Warsaw, Poland in the years 1989-2009
      registering the number of patients treated for various mental disorders in public
      facilities in Poland. Temporal trend analysis of the annual number of patients
      with a diagnosis of psychotic disorders, who were treated at outpatient clinics,
      was performed. RESULTS: We found a statistically significant increase in the
      total number of recorded schizophrenia patients treated at outpatient clinics, as
      well as in the number of patients treated for the first time at outpatient
      clinics for schizophrenia. These changes overlap with the implementation of the
      reimbursement policy for SGA. CONCLUSION: Our results suggest that the restricted
      reimbursement policy for SGA altered the diagnosing process in Poland. It seems
      that these alterations may have serious social consequences. Given that a
      diagnosis of schizophrenia is more stigmatizing than a diagnosis of other
      psychotic disorders, it might be assumed that schizophrenia over-diagnosing,
      possibly due to reimbursement reasons, add to the enormous burden associated with
      stigmatization.

PMID- 24022755
TI  - Regulation of MEIS1 by distal enhancer elements in acute leukemia.
AB  - Aberrant activation of the three-amino-acid-loop extension homeobox gene MEIS1
      shortens the latency and accelerates the onset and progression of acute leukemia,
      yet the molecular mechanism underlying persistent activation of the MEIS1 gene in
      leukemia remains poorly understood. Here we used a combined comparative genomics
      analysis and an in vivo transgenic zebrafish assay to identify six regulatory DNA
      elements that are able to direct green fluorescent protein expression in a
      spatiotemporal manner during zebrafish embryonic hematopoiesis. Analysis of
      chromatin characteristics and regulatory signatures suggests that many of these
      predicted elements are potential enhancers in mammalian hematopoiesis.
      Strikingly, one of the enhancer elements (E9) is a frequent integration site in
      retroviral-induced mouse acute leukemia. The genomic region corresponding to
      enhancer E9 is differentially marked by H3K4 monomethylation and H3K27
      acetylation, hallmarks of active enhancers, in multiple leukemia cell lines.
      Decreased enrichment of these histone marks is associated with downregulation of
      MEIS1 expression during hematopoietic differentiation. Further, MEIS1/HOXA9
      transactivate this enhancer via a conserved binding motif in vitro, and
      participate in an autoregulatory loop that modulates MEIS1 expression in vivo.
      Our results suggest that an intronic enhancer regulates the expression of MEIS1
      in hematopoiesis and contributes to its aberrant expression in acute leukemia. 

PMID- 24022756
TI  - Effect of catheter movement and contact during application of radiofrequency
      energy on ablation lesion characteristics.
AB  - BACKGROUND: The efficient delivery of radiofrequency (RF) energy through an
      endocardial ablation catheter is affected by variable tissue contact due to
      cardiac motion with myocardial contraction and respiration. In addition, many
      operators intentionally move an ablation catheter during the delivery of
      radiofrequency energy when targeting specific arrhythmias that require lines of
      conduction block such as atrial flutter and atrial fibrillation. We sought to
      characterize and quantify any effects of catheter movement and intermittent
      ablation catheter contact on lesion characteristics. METHODS: An ex vivo model
      consisting of recently excised viable bovine myocardium, a circulating saline
      bath at 37  degrees C, a submersible load cell, and a deflectable sheath with an
      ablation catheter was assembled. A stepper motor attached to an ablation catheter
      apparatus was programmed to simulate linear drag lesions and series of point
      lesions with variable contact using constant force. Lesion volumes were analyzed
      using a digital micrometer by measuring depth, max width, depth at max width, and
      surface width and compared. RESULTS: The drag lesion was significantly larger
      than a pointby-point linear lesion using a constant force of 15 g (2,088+/- 122
      mm3 vs. 1,595+/-121.6; p =0.01) when controlling for RF time and power. For
      single point lesion assessment, constant contact lesions were significantly
      larger than lesions created with intermittent contact using the same duration of
      RF (194+/- 68 mm3 vs. 112.5+/-53; p =0.03). There was no significant difference
      in lesion size between the constant contact at 60 s and 90-s intermittent contact
      lesions (194+/-68 mm3 vs.186+/-69). CONCLUSIONS: In our ex vivo model, externally
      irrigated radiofrequency catheters produced drag lesion volumes equal to or
      larger than those created by a point-by-point method.We also found decreased
      lesion size due to intermittent contact can be overcome by increasing duration of
      ablation time.

PMID- 24022757
TI  - Clinical significance of increased tricuspid valve incompetence following
      implantation of ventricular leads.
AB  - PURPOSE: Cardiac rhythm management devices (CRMD) require a ventricular lead to
      be placed across the tricuspid valve. Tricuspid regurgitation (TR) is an under
      recognized clinical complication of lead implantation and its clinical
      significance is unknown. We studied the incidence of hospitalizations for
      congestive heart failure (CHF) exacerbation among patients with worsening TR
      after ventricular lead implantation. METHODS: We reviewed 148 patients (age 68 +/
      15) that received a CRMD. TR and pulmonary artery systolic pressure (PASP)
      measured by Doppler echocardiography before and after CRMD implantation were
      analyzed. Hospitalizations for CHF exacerbation post-implantation were counted.
      RESULTS: Follow-up was 32 +/- 14 months. Ninety-nine (67%) patients had no
      change, 24 (16%) slight, and 9 (6%) significant increase in TR after CRMD
      implantation, while 13 (9%) patients had slight and 3 (2%) significant
      improvement. Patients with a significant increase in TR had higher incidence of
      hospitalizations (1.7 +/- 0.5) compared to patients with slight (0.8 +/- 1; p =
      0.006) or no increase (0.5 +/- 1; p = 0.0002) in TR. Patients with significant
      increase in TR had a greater change in PASP (25 mmHg; p = 0.002) after device
      implantation compared to those with a slight (10 mmHg; p = 0.002) or no increase
      (0.7 mmHg; p = 0.17). CONCLUSION: Increased TR following CRMD implantation is
      relatively common (33%) and correlated with subsequent risk of hospitalization
      for heart failure. A preventive strategy and close monitoring for development or
      worsening of CHF after CRMD implantation may help prevent hospital admissions.

PMID- 24022758
TI  - The first reported case of G6PD deficiency due to Seoul  mutation in Poland.

PMID- 24022759
TI  - Heat-induced antigen retrieval: an effective method to detect and identify
      progenitor cell types during adult hippocampal neurogenesis.
AB  - Traditional methods of immunohistochemistry (IHC) following tissue fixation allow
      visualization of various cell types. These typically proceed with the application
      of antibodies to bind antigens and identify cells with characteristics that are a
      function of the inherent biology and development. Adult hippocampal neurogenesis
      is a sequential process wherein a quiescent neural stem cell can become activated
      and proceed through stages of proliferation, differentiation, maturation and
      functional integration. Each phase is distinct with a characteristic morphology
      and upregulation of genes. Identification of these phases is important to
      understand the regulatory mechanisms at play and any alterations in this process
      that underlie the pathophysiology of debilitating disorders. Our heat-induced
      antigen retrieval approach improves the intensity of the signal that is detected
      and allows correct identification of the progenitor cell type. As discussed in
      this paper, it especially allows us to circumvent current problems in detection
      of certain progenitor cell types. 

PMID- 24022760
TI  - Chemical composition and biological activity of the essential oil from leaves of
      Moringa oleifera Lam. cultivated in Mozambique.
AB  - The antioxidant capacity and antimicrobial activity of the essential oil of
      Moringa oleifera (Moringaceae) grown in Mozambique was investigated. The chemical
      composition was studied by means of GC and GC-MS analysis. Hexacosane (13.9%),
      pentacosane (13.3%) and heptacosane (11.4%) were the main components. Ultra High
      Performance Chromatography-DAD analysis detected the flavonoids quercetin (126
      MUg/g) and luteolin (6.2 MUg/g). The essential oil exhibited a relatively low
      free radical scavenging capacity. The antimicrobial activity of the essential oil
      was assayed against two Gram-positive strains (Bacillus cereus, Staphylococcus
      aureus), two Gram-negative strains (Escherichia coli, Pseudomonas aeruginosa),
      and five fungal strains of agro-food interest (Penicillium aurantiogriseum,
      Penicillium expansum, Penicillium citrinum, Penicillium digitatum, and
      Aspergillus niger spp.). B. cereus and P. aeruginosa, as well as the fungal
      strains were sensitive to the essential oil.

PMID- 24022761
TI  - Retraction: Al-Salahi, R.A. et al. Cytotoxicity and anti-inflammatory activity of
      ethylsulfanyltriazoloquinazolines. Molecules 2013, 18, 1434-1446.
AB  - We have been made aware of the fact that a large proportion of the Introduction
      section and corresponding references of the title paper [1] had been copied
      verbatim from an earlier paper by Hamdy and Gamal-Eldeen [2], and further, during
      our investigation it has also come to light that most of the text in question had
      been lifted unchanged from an even earlier review paper by a different group [3].
      The authors have been contacted, these facts confirmed, and Dr. Amira M. Gamal
      Eldeen has been identified as the person responsible for contributing that part
      of the paper. As a member of the Committee on Publication Ethics (COPE), MPDI
      takes very seriously the responsibility to enforce a rigorous peer-review process
      together with strict ethical policies and standards to ensure the addition of
      high quality scientific works to the field of scholarly publication. In addition
      to an infringement of the Elsevier and American Association for Cancer Research
      copyright on the previous publications, this is also a clear violation of our
      policy to only publish new, previously unpublished material, so this paper is
      declared retracted and shall be marked accordingly for the scientific record. We
      cannot comment on any of the scientific data contained in the Molecules paper,
      which to the best of our knowledge is original. We would like to apologize to our
      readership on behalf of the Molecules editorial team for the fact this event went
      undetected during the peer-review and pre-publication processing of the paper and
      for any inconvenience caused by this event.

PMID- 24022762
TI  - Antioxidant and anti-fatigue activities of phenolic extract from the seed coat of
      Euryale ferox Salisb. and identification of three phenolic compounds by LC-ESI
      MS/MS.
AB  - This study investigated the antioxidant potential and anti-fatigue effects of
      phenolics extracted from the seed coat of Euryale ferox Salisb. The in vitro
      antioxidant potentials, including scavenging DPPH, hydroxyl radical activities
      and reducing power were evaluated. Antioxidant status in vivo was analyzed by
      SOD, CAT, GSH-Px activities and the MDA content in liver and kidneys of D
      galactose-induced aging mice. The anti-fatigue effect was evaluated using an
      exhaustive swimming test, along with the determination of LDH, BUN and HG
      content. The phenolic extract possessed notable antioxidant effects on DPPH,
      hydroxyl radical scavenging and reducing power. The mice which received the
      phenolic extract showed significant increases of SOD, CAT (except for in the
      kidney), GSH-Px activities, and a decrease of MDA content. The average exhaustive
      swimming time was obviously prolonged. Meanwhile, increase of LDH content and
      decrease of BUN content were observed after mice had been swimming for 15 min.
      The HG storage of mice was improved in the high and middle dose extract groups
      compared with the normal group. The contents of total phenols and gallic acid of
      the extract were determined. Three compounds in the extract were identified as
      5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-chroman-4-one, 5,7,4-trihydroxyflavanone
      and buddlenol E. These results suggest that the extract of E. ferox is a
      promising source of natural antioxidants and anti-fatigue material for use in
      functional foods and medicines. 

PMID- 24022763
TI  - The inhibitory effects of phenolic and terpenoid compounds from Baccharis trimera
      in Siha cells: differences in their activity and mechanism of action.
AB  - Baccharis trimera is used in folk medicine as a tea for digestive and liver
      diseases. It possesses anti-inflammatory and antioxidant properties that are
      related to the presence of phenolic compounds. The aim of this work was to
      investigate the anti-proliferative properties of phenolic (PHE) and terpenoid
      (SAP) compounds from B. trimera on human cervical cancer. The treatment of SiHa
      cells with PHE for 24 h suppressed colony formation in a dose-dependent manner,
      inhibited proliferation and inhibited cell motility. Although SAP inhibited the
      proliferation of SiHa cells in a dose-dependent manner, it increased colony
      formation and did not inhibit cell motility. PHE and SAP also promoted a
      significant increase in lactate dehydrogenase levels in the culture medium in a
      dose-dependent manner, indicating a loss of cell membrane integrity. Moreover,
      PHE promoted necrotic cell death, whereas SAP induced apoptosis. These compounds
      are new anticancer prototypes due their significant anticancer activity
      demonstrated herein. 

PMID- 24022764
TI  - Microwave assisted dyeing of polyester fabrics with disperse dyes.
AB  - Dyeing of polyester fabrics with thienobenzochromene disperse dyes under
      conventional and microwave heating conditions was studied in order to determine
      whether microwave heating could be used to enhance the dyeability of polyester
      fabrics. Fastness properties of the dyed samples were measured. All samples dyed
      with or without microwave heating displayed excellent washing and perspiration
      fastness. The biological activities of the synthesized dyes against Gram positive
      bacteria, Gram negative bacteria, yeast and fungus were also evaluated.

PMID- 24022765
TI  - Civil, sensible, and constructive peer review in APS journals.

PMID- 24022766
TI  - Explorations in statistics: the analysis of ratios and normalized data.
AB  - Learning about statistics is a lot like learning about science: the learning is
      more meaningful if you can actively explore. This ninth installment of
      Explorations in Statistics explores the analysis of ratios and normalized-or
      standardized-data. As researchers, we compute a ratio-a numerator divided by a
      denominator-to compute a proportion for some biological response or to derive
      some standardized variable. In each situation, we want to control for differences
      in the denominator when the thing we really care about is the numerator. But
      there is peril lurking in a ratio: only if the relationship between numerator and
      denominator is a straight line through the origin will the ratio be meaningful.
      If not, the ratio will misrepresent the true relationship between numerator and
      denominator. In contrast, regression techniques-these include analysis of
      covariance-are versatile: they can accommodate an analysis of the relationship
      between numerator and denominator when a ratio is useless. 

PMID- 24022767
TI  - Space physiology within an exercise physiology curriculum.
AB  - Compare and contrast strategies remain common pedagogical practices within
      physiological education. With the support of an American Physiological Society
      Teaching Career Enhancement Award, we have developed a junior- or senior-level
      undergraduate curriculum for exercise physiology that compares and contrasts the
      physiological adaptations of chronic terrestrial exercise (TEx) and microgravity
      (MUG). We used a series of peer-reviewed publications to demonstrate that many of
      the physiological adaptations to TEx and MUG are opposite. For example, TEx
      typically improves cardiovascular function and orthostatic tolerance, whereas MUG
      can lead to declines in both. TEx leads to muscle hypertrophy, and MUG elicits
      muscle atrophy. TEx increases bone mineral density and red blood cell mass,
      whereas MUG decreases bone mineral density and red blood cell mass. Importantly,
      exercise during spaceflight remains a crucial countermeasure to limit some of
      these adverse physiological adaptations to MUG. This curriculum develops critical
      thinking skills by dissecting peer-reviewed articles and discussing the strengths
      and weaknesses associated with simulated and actual MUG studies. Moreover, the
      curriculum includes studies on both animals and humans, providing a strong
      translational component to the curriculum. In summary, we have developed a novel
      space physiology curriculum delivered during the final weeks of an exercise
      physiology course in which students gain critical new knowledge that reinforces
      key concepts presented throughout the semester. 

PMID- 24022768
TI  - Higher levels of intrinsic motivation are related to higher levels of class
      performance for male but not female students.
AB  - Our students are naturally curious, with powerful intrinsic motives to understand
      their world. Accordingly, we, as teachers, must capitalize on this inherently
      active and curious nature so that learning becomes a lifelong activity where
      students take initiative for learning, are skilled in learning, and want to learn
      new things. Achieving this goal requires an understanding of student attitudes,
      beliefs, characteristics, and motivations. To achieve this goal, we administered
      the intrinsic motivation inventory (IMI) to assess our students' interest and
      enjoyment, perceived choice, and perceived competence while taking our
      undergraduate exercise physiology class (46 students; 20 female students and 26
      male students). The interest and enjoyment subscale is considered the self
      reported measure of intrinsic motivation. The perceived choice and perceived
      competence concepts are theorized to be positive predictors of both self-reported
      and behavioral measures of intrinsic motivation. Our results documented a
      significant increase in course grade with an increase in survey score for the
      interest and enjoyment subscale of the IMI when female and male students were
      combined. Specifically, each increase in survey score for the interest and
      enjoyment subscale of the IMI was associated with a significant (P < 0.05)
      increase of 3.9% in course grade. However, the increase in survey score was
      associated with a significantly greater (P < 0.05) increase in course grade for
      male (6.1%) compared with female (0.3%) students. These results have implications
      for both classroom practice and educational reform policies. 

PMID- 24022769
TI  - Process-oriented guided-inquiry learning improves long-term retention of
      information.
AB  - Many chemistry educators have adopted the process-oriented guided instructional
      learning (POGIL) pedagogy. However, it is not clear which aspects of POGIL are
      the most important in terms of actual learning. We compared 354 first-year
      undergraduate psychology students' learning in physiological psychology using
      four teaching methods: control, POGIL, POGIL without reporting [no report out
      (NRO)], and POGIL run by untrained graduate students [new facilitator (NF)].
      Student activities were identical across POGIL variations and highly similar for
      control. Participants' knowledge was evaluated before (pretest), immediately
      after (posttest), and 2 wk later (followup). Control and POGIL groups showed no
      improvement at posttest, whereas NRO and NF groups both recalled more material
      than at pretest (P = 0.002 and P < 0.0005, respectively). In a surprise test 2 wk
      later, control (P < 0.0005), NRO (P = 0.03), and NF (P < 0.0005) groups recalled
      less than at posttest. The POGIL group showed the smallest drop in knowledge (P =
      0.05). Importantly, the control group's knowledge was below pretest levels (P <
      0.0005), whereas the POGIL, NRO, and NF groups' knowledge was not. Self
      assessment of knowledge was consistent across groups at pretest, but POGIL
      participants had the lowest confidence at posttest and 2 wk later. At followup,
      the control, NRO, and NF groups showed greater confidence in their knowledge than
      the POGIL group (P = 0.03, P = 0.002, and P = 0.004, respectively). POGIL and its
      variations appear to consolidate existing knowledge against memory decay even
      when student confidence does not match performance. 

PMID- 24022770
TI  - An efficient approach to improve the usability of e-learning resources: the role
      of heuristic evaluation.
AB  - Optimizing the usability of e-learning materials is necessary to maximize their
      potential educational impact, but this is often neglected when time and other
      resources are limited, leading to the release of materials that cannot deliver
      the desired learning outcomes. As clinician-teachers in a resource-constrained
      environment, we investigated whether heuristic evaluation of our multimedia e
      learning resource by a panel of experts would be an effective and efficient
      alternative to testing with end users. We engaged six inspectors, whose expertise
      included usability, e-learning, instructional design, medical informatics, and
      the content area of nephrology. They applied a set of commonly used heuristics to
      identify usability problems, assigning severity scores to each problem. The
      identification of serious problems was compared with problems previously found by
      user testing. The panel completed their evaluations within 1 wk and identified a
      total of 22 distinct usability problems, 11 of which were considered serious. The
      problems violated the heuristics of visibility of system status, user control and
      freedom, match with the real world, intuitive visual layout, consistency and
      conformity to standards, aesthetic and minimalist design, error prevention and
      tolerance, and help and documentation. Compared with user testing, heuristic
      evaluation found most, but not all, of the serious problems. Combining heuristic
      evaluation and user testing, with each involving a small number of participants,
      may be an effective and efficient way of improving the usability of e-learning
      materials. Heuristic evaluation should ideally be used first to identify the most
      obvious problems and, once these are fixed, should be followed by testing with
      typical end users. 

PMID- 24022771
TI  - Evaluating learning among undergraduate medical students in schools with
      traditional and problem-based curricula.
AB  - This study aimed to assess knowledge and skills in a respiratory physiology
      course in traditional versus problem-based learning (PBL) groups in two different
      medical schools. Two different undergraduate medical schools were selected for
      this study. The first medical school followed the traditional [lecture-based
      learning (LBL)] curriculum, and the second medical school followed the PBL
      curriculum. Sixty first-year male medical students (30 students from each medical
      school) volunteered; they were apparently healthy and of the same age, sex,
      nationality, and regional and cultural background. Students were taught
      respiratory physiology according to their curriculum for a period of 2 wk. At the
      completion of the study period, knowledge was measured based on a single best
      multiple-choice question examination, and skill was measured based on the
      objective structured practical examination in the lung function laboratory
      (respiratory physiology). A Student's t-test was applied for the analysis of the
      data, and the level of significance was set at P < 0.05. Students belonging to
      the PBL curriculum obtained a higher score in the multiple-choice question
      examination (P = 0.001) and objective structured practical examination (P =
      0.0001) compared with traditional (LBL) students. Students in the PBL group
      obtained significantly higher knowledge and skill scores in the respiratory
      physiology course compared with students in the traditional (LBL) style of
      medical schools. 

PMID- 24022772
TI  - Laboratory exercise: study of digestive and regulatory processes through the
      exploration of fasted and postprandial blood glucose.
AB  - Digestive physiology laboratory exercises often explore the regulation of enzyme
      action rather than systems physiology. This laboratory exercise provides a
      systems approach to digestive and regulatory processes through the exploration of
      postprandial blood glucose levels. In the present exercise, students enrolled in
      an undergraduate animal physiology course select to participate in either an oral
      glucose tolerance test (OGTT) or one of the following three meal treatments based
      on typical student breakfasts: 1) high glycemic load (HGL), 2) moderate glycemic
      load (MGL), and 3) low glycemic load (LGL). The caloric value of the meals is 540
      kcal. An Accucheck glucometer is used to determine fasted and 30-, 60-, and 120
      min postprandial blood glucose levels. Students discover that postprandial
      glucose levels peak similarly for the OGTT and HGL group (137 +/- 7.1 and 145 +/-
      4.7mg/dl) and remain higher than MGL and LGL groups over the 2-h period. Between
      sampling, vibrant discussion covering such topics as glucose and cognitive
      function, insulin resistance, epigenetics, and fad diets occurs. The
      postlaboratory assignment requires students to discuss the importance of glucose
      homeostasis, graphically summarize their findings, review the literature to
      describe results in light of published data, and describe relationships between
      hyperglycemia and hyperinsulinemia and disease processes. Students evaluated this
      laboratory as highly effective and one of the top three experiences of the
      course. 

PMID- 24022773
TI  - Using an essay competition as an alternative tool for enhancing the "learning
      from learners" teaching approach.

PMID- 24022774
TI  - The role of equal pressure points in understanding pulmonary diseases.

PMID- 24022775
TI  - The concept of clearance: an alternative teaching-learning method.

PMID- 24022778
TI  - Purification and characterization of tyrosine phenol lyase from Citrobacter
      freundii.
AB  - The purification and characterization of intracellular tyrosine phenol lyase from
      Citrobacter freundii has been carried out. The enzyme was purified 35-fold to
      homogeneity by ammonium sulphate precipitation and hydrophobic interaction
      chromatography. Its subunit molecular weight was found to be 52 kDa on sodium
      dodecyl sulphate polyacrylamide gel electrophoresis. The purified tyrosine phenol
      lyase showed maximum activity in borate buffer (0.05 M at pH 8.5) at 45  degrees
      C after 20 min of incubation. The Km and Vmax values of purified enzyme were
      found to be 0.446 mm and 0.342 mM/min/mg. This enzyme exhibits t1/2 of 10, 52 and
      130 min at 55, 45 and 35  degrees C, respectively. The N-terminal amino acid
      sequence was determined as MET-ASN-TYR-PRO-ALA-GLU-PRO-PHE-ARG-ILETRP- TRP-VAL
      GLY.

PMID- 24022779
TI  - Characteristics of a high maltose-forming, acid-stable, and Ca(2+)-independent
      alpha-amylase of the acidophilic Bacillus acidicola.
AB  - The purified acidic alpha-amylase of Bacillus acidicola is a monomer of 66.0 kDa,
      optimally active at pH 4.0 and 60  degrees C. The enzyme is Ca2+ independent with
      T1/2 for 18 min at 80  degrees C. The Km, Vmax, and catalytic efficiency
      (kcat/Km) of the enzyme are 1.6 mg mL(-1), 23.8 MUmol mg(-1) min(-1), and 981
      MUmol s(-1), respectively. Among detergents, Tween 20, 40, and 80 stimulated
      enzyme activity, whereas sodium dodecyl sulfate and Triton X-100 inhibited even
      at low concentration. EGTA has not affected the activity, whereas EDTA beta
      mercaptoethanol, iodoacetic acid, and Dithiothreitol exhibited a slight
      inhibitory action. Phenylmethanesulfonyl fluoride, N-bromosuccinimide, and Hg2+
      strongly inhibited enzyme activity. The experimental activation energy and
      temperature quotient are 50.12 kJ mol(-1) and 1.37. When thermodynamic parameters
      (DeltaH and DeltaS) of the enzyme have been determined at different temperatures,
      DeltaG is positive suggesting that the enzyme is thermostable. The enzyme
      hydrolyzes raw starches, and therefore, the enzyme finds application in raw
      starch saccharification at sub-gelatinization temperatures that saves energy
      needed for gelatinization of raw starch at 105  degrees C.

PMID- 24022780
TI  - Regional differences in rice hulls supply for bioethanol production.
AB  - Agricultural by-products are becoming an attractive substrate for bioethanol
      production. The aim of this study was to evaluate the effects of regional
      differences in the rice hulls using Escherichia coli KO11 for bioethanol
      production. The rice hulls coded Edirne were obtained from Thrace Region, and the
      rice hulls coded Izmir were obtained from Aegean Region in Turkey. Rice hulls
      were treated by dilute acid before using them as substrates. The cells were
      incubated on an orbital shaker at 160 rpm under 30  degrees C during 96 h of the
      fermentation period. It was found that the maximum yield of ethanol from sugar
      (0.44 g ethanol/g reducing sugar) was obtained with the substrate C/N ratio of
      29.16 in Izmir medium. The main difference was the dominant carbon source
      available as a substrate. It was detected that glucose concentration was about
      2.5 times higher in Izmir medium, whereas xylose concentration was about two
      times higher in Edirne medium. The different results obtained with rice hulls
      from different origins could depend on the type of paddy as well as different
      cultivation conditions. These findings provide a valuable indicator for
      identifying suitable agricultural waste materials to be used as substrates for
      bioethanol production.

PMID- 24022781
TI  - Solid-state fermentation of rapeseed meal with the white-rot fungi trametes
      versicolor and Pleurotus ostreatus.
AB  - Rapeseed meal is valuable high-protein forage, but its nutritional value is
      significantly reduced by the presence of a number of antinutrients, including
      phenolic compounds. Solid-state fermentation with white-rot fungi was used to
      decrease the sinapic acid concentration of rapeseed meal. After 7 days of growth
      of Trametes versicolor and Pleurotus ostreatus, the sinapic acid content of
      rapeseed meal was reduced by 59.9 and 74.5 %, respectively. At the end of the
      experiment, sinapic acid concentration of T. versicolor cultures decreased by
      93%of the initial value; in the case of cultures of P. ostreatus, 93.2 %
      reduction was observed. Moreover, cultivation of white-rot fungi on rapeseed meal
      resulted in the intensive production of extracellular laccase, particularly
      strong during the late phases of growth of T. versicolor. The obtained results
      confirm that both fungal species may effectively be used to decompose
      antinutritional phenolics of rapeseed meal. Rapeseed meal may also find use as an
      inexpensive and efficient substrate for a biotechnological production of laccase
      by white-rot fungi.

PMID- 24022782
TI  - Theoretical investigation on the kinetics and branching ratio of the gas phase
      reaction of sevoflurane with Cl atom.
AB  - The present work deals with the theoretical investigation on the Cl initiated H
      atom abstraction reaction of sevoflurane, (CF3)2CHOCH2F. A dual-level procedure
      has been adopted for studying the kinetics of the reaction. Geometrical
      optimization and frequency calculation were performed at DFT(BHandHLYP)/6
      311G(d,p) while single-point energy calculation was made at CCSD(T)/6-311G(d,p)
      level of theory. The intrinsic reaction coordinate (IRC) calculation has also
      been performed to confirm the smooth transition from the reactant to product
      through the respective transition state. The rate constants were calculated using
      conventional transition state theory (TST). It has been found that 99 % of the
      reaction proceeded via the H-atom abstraction from the -CH2F end of the
      sevoflurane. The rate constant of the dominant path is found to be 1.13 * 10-13
      cm3 molecule-1 s-1. This is in excellent agreement with the reported experimental
      rate constant of 1.10 * 10-13 cm3 molecule-1 s-1 obtained by relative rate method
      using FTIR/Smog chamber and LP/LIF techniques.

PMID- 24022784
TI  - Profiling human Src homology 2 (SH2) domain proteins and ligand discovery using a
      peptide-hybrid small molecule microarray.
AB  - A 396-member peptide-hybrid small molecule microarray was fabricated to profile
      small molecule ligands across 15 SH2 proteins, revealing hits against Lck and
      Grb2. 

PMID- 24022783
TI  - Design of Lewis acid-base complex: enhancing the stability and first
      hyperpolarizability of large excess electron compound.
AB  - In the present paper, a new type of Lewis acid-base complex
      BX3...Li@Calix[4]pyrrole (X = H and F) was designed and assembled based on
      electride molecule Li@calix[4]pyrrole (as a Lewis base) and the electron
      deficient molecule BX3 (as a Lewis acid) by employing quantum mechanical
      calculation. The new Lewis acid-base complex offers an interesting push-excess
      electron-pull (P-e-P) framework to enhance the stability and nonlinear optical
      (NLO) response. To measure the nonlinear optical response, static first
      hyperpolarizabilities (beta 0) are exhibited. Significantly, point-face assembled
      Lewis acid-base complex BF3...Li@Calix[4]pyrrole (II) has considerable first
      hyperpolarizabilities (beta 0) value (1.4  *  106 a.u.), which is about 117 times
      larger than reported 11,721 a.u. of electride Li@Calix[4]pyrrole. Further
      investigations show that, in BX3...Li@Calix[4]pyrrole with P-e-P framework, a
      strong charge-transfer transition from the ground state to the excited state
      contributes to the enhancement of first hyperpolarizability. Theory calculation
      of enthalpies of reaction (DeltarH0) at 298 K demonstrates that it is feasible to
      synthetize the complexes BX3...Li@Calix[4]pyrrole. In addition, compared with
      Li@Calix[4]pyrrole, the vertical ionization potential (VIP) and HOMO-LUMO gap of
      BX3...Li@Calix[4]pyrrole have obviously increased, due to the introduction of the
      Lewis acid molecule BX3. The novel Lewis acid-base NLO complex possesses not only
      a large nonlinear optical response but also higher stability.

PMID- 24022785
TI  - Tailoring the oxidation state of cobalt through halide functionality in sol-gel
      silica.
AB  - The functionality or oxidation state of cobalt within a silica matrix can be
      tailored through the use of cationic surfactants and their halide counter ions
      during the sol-gel synthesis. Simply by adding surfactant we could significantly
      increase the amount of cobalt existing as Co3O4 within the silica from 44% to
      77%, without varying the cobalt precursor concentration. However, once the
      surfactant to cobalt ratio exceeded 1, further addition resulted in an inhibitory
      mechanism whereby the altered pyrolysis of the surfactant decreased Co3O4
      production. These findings have significant implications for the production of
      cobalt/silica composites where maximizing the functional Co3O4 phase remains the
      goal for a broad range of catalytic, sensing and materials applications. 

PMID- 24022786
TI  - Chiral self-assembly and reversible light modulation of a polyoxometalate complex
      via host-guest recognition.
AB  - Chiral self-assembly of an azobenzene-grafted POM complex has been constructed
      through self-crosslinking by both the electrostatic and host-guest interactions
      and reversibly modulated by dynamic controlling of the isomerization of
      photoactive groups in the complex. 

PMID- 24022787
TI  - Clinical characteristics, response to therapy, and survival of African American
      patients diagnosed with chronic lymphocytic leukemia: joint experience of the MD
      Anderson Cancer Center and Duke University Medical Center.
AB  - BACKGROUND: Little is known regarding racial disparities in characteristics and
      outcomes among patients with chronic lymphocytic leukemia (CLL). METHODS: The
      characteristics and outcomes of untreated African American (AA) patients with CLL
      (n = 84) were analyzed and compared with a reference nonblack (NB) patient
      population (n = 1571). RESULTS: At the time of presentation, AA patients had
      lower median hemoglobin levels (12.9 g/dL vs 13.7 g/dL), higher beta2
      microglobulin levels (2.7 mg/dL vs 2.4 mg/dL), greater frequency of
      constitutional symptoms (27% vs 10%), unmutated immunoglobulin heavy-chain
      variable region (IGHV) mutation status (65% vs 47%), zeta-chain-associated
      protein kinase 70 (ZAP70) expression (58% vs 32%), and deletion of chromosome 17p
      or chromosome 11q (28% vs 17%; P <= 02 for each comparison). Fifty-one percent of
      AA patients and 39% of NB patients required first-line therapy and 91% and 88%,
      respectively, received chemoimmunotherapy. Overall response rates to treatment
      were 85% for AA patients and 94% for NB patients (P = .06); and the complete
      response rates were 56% and 58%, respectively (P = .87). The median survival of
      AA patients was shorter compared with that of NB patients (event-free survival:
      36 months vs 61 months; P = .007; overall survival: 152 months vs not reached; P
      = .0001). AA race was an independent predictor of shorter event-free and overall
      survival in multivariable regression models. CONCLUSIONS: The current results
      indicated that AA patients with CLL have more unfavorable prognostic
      characteristics and shorter survival compared with their NB counterparts.

PMID- 24022788
TI  - Activation of the ubiquitin proteasome pathway in a mouse model of inflammatory
      myopathy: a potential therapeutic target.
AB  - OBJECTIVE: Myositis is characterized by severe muscle weakness. We and others
      have previously shown that endoplasmic reticulum (ER) stress plays a role in the
      pathogenesis of myositis. The present study was undertaken to identify perturbed
      pathways and assess their contribution to muscle disease in a mouse myositis
      model. METHODS: Stable isotope labeling with amino acids in cell culture (SILAC)
      was used to identify alterations in the skeletal muscle proteome of myositic mice
      in vivo. Differentially altered protein levels identified in the initial
      comparisons were validated using a liquid chromatography tandem mass spectrometry
      spike-in strategy and further confirmed by immunoblotting. In addition, we
      evaluated the effect of a proteasome inhibitor, bortezomib, on the disease
      phenotype, using well-standardized functional, histologic, and biochemical
      assessments. RESULTS: With the SILAC technique we identified significant
      alterations in levels of proteins belonging to the ER stress response, ubiquitin
      proteasome pathway (UPP), oxidative phosphorylation, glycolysis, cytoskeleton,
      and muscle contractile apparatus categories. We validated the myositis-related
      changes in the UPP and demonstrated a significant increase in the ubiquitination
      of muscle proteins as well as a specific increase in ubiquitin carboxyl-terminal
      hydrolase isozyme L1 (UCHL-1) in myositis, but not in muscle affected by other
      dystrophies or normal muscle. Inhibition of the UPP with bortezomib significantly
      improved muscle function and also significantly reduced tumor necrosis factor
      alpha expression in the skeletal muscle of mice with myositis. CONCLUSION: Our
      findings indicate that ER stress activates downstream UPPs and contributes to
      muscle degeneration and that UCHL-1 is a potential biomarker for disease
      progression. UPP inhibition offers a potential therapeutic strategy for myositis.

PMID- 24022789
TI  - CD8+ cells regulate the T helper-17 response in an experimental murine model of
      Sjogren syndrome.
AB  - This study investigated the regulatory function of CD8+ cells in T helper-17
      (Th17) cell-mediated corneal epithelial barrier disruption that develops in a
      murine desiccating stress (DS) model that resembles Sjogren syndrome. CD8+ cell
      depletion promoted generation of interleukin-17A (IL-17A)-producing CD4+ T cells
      via activation of dendritic cells in both the ocular surface and draining
      cervical lymph nodes in C57BL/6 mice subjected to DS. T-cell-deficient nude
      recipient mice receiving adoptively transferred CD4+ T cells from CD8+ cell
      depleted donors exposed to DS displayed increased CD4+ T-cell infiltration and
      elevated IL-17A and CC-chemokine attractant ligand 20 levels in the ocular
      surface, which was associated with greater corneal barrier disruption. Enhanced
      DS-specific corneal barrier disruption in CD8-depleted donor mice correlated with
      a Th17-mediated expression of matrix metalloproteinases (MMP-3 and MMP-9) in the
      recipient corneal epithelium. Co-transfer of CD8+CD103+ regulatory T cells did
      not affect the ability of DS-specific pathogenic CD4+ T cells to infiltrate and
      cause ocular surface disease in the nude recipients, showing that CD8+ cells
      regulate the efferent arm of DS-induced immune response. In summary, CD8+
      regulatory cells suppress generation of a pathogenic Th17 response that has a
      pivotal role in DS-induced disruption of corneal barrier function.

PMID- 24022790
TI  - Health-related quality of life (HRQL) in immunodeficient adults with selective
      IgA deficiency compared with age- and gender-matched controls and identification
      of risk factors for poor HRQL.
AB  - PURPOSE: Selective IgA deficiency (SIgAD) is the most common primary
      immunodeficiency with a prevalence of 1/600 in the general population. Any
      targeted health-related quality of life (HRQL) study of adults with SIgAD has
      never been presented. The objectives of the study were to compare HRQL between
      SIgAD adults and randomly selected age- and gender-matched population controls,
      and to identify risk factors for poor HRQL. METHODS: Thirty-two SIgAD individuals
      and 63 controls answered three questionnaires (clinical data, Short Form-36
      Health Survey (SF-36), infection-related HRQL) at baseline before undergoing
      medical/dental examinations and laboratory assessments. HRQL in SIgAD was re
      evaluated after 6 and 12 months. RESULTS: Baseline: Selective IgA deficiency
      individuals reported significantly increased fear of contracting infections (p <
      0.01). Those scoring high on fear also perceived significantly poorer physical
      health (p < 0.01). SF-36 results indicated that SIgAD individuals perceived
      poorer HRQL, although this was not statistically significant. FOLLOW-UP: Compared
      with SF-36 responses at baseline, SIgAD individuals reported significantly more
      pain (p < 0.01) at 6 months, poorer general health (p < 0.05) and summarised
      physical HRQL (p < 0.01) at 6 and 12 months and decreased vitality at 12 months.
      The summarised mental scale remained stable over time. Risk factors for poor
      HRQL: The number of antibiotic treatments during the previous year (p < 0.001),
      number of daily medications (p < 0.01), allergic rhinoconjunctivitis (p < 0.05),
      chronic musculoskeletal symptoms at least every week (p < 0.05) and anxiety
      and/or insomnia (p < 0.05) were identified as independent risk factors for poor
      HRQL. CONCLUSION: The study highlights the importance of identifying and
      thoroughly evaluating, educating and following up individuals with SIgAD, as
      their HRQL may be negatively affected due to health problems possible to prevent
      and treat.

PMID- 24022791
TI  - Quantifying the reliability of image replication studies: the image intraclass
      correlation coefficient (I2C2).
AB  - This article proposes the image intraclass correlation (I2C2) coefficient as a
      global measure of reliability for imaging studies. The I2C2 generalizes the
      classic intraclass correlation (ICC) coefficient to the case when the data of
      interest are images, thereby providing a measure that is both intuitive and
      convenient. Drawing a connection with classical measurement error models for
      replication experiments, the I2C2 can be computed quickly, even in high
      dimensional imaging studies. A nonparametric bootstrap procedure is introduced to
      quantify the variability of the I2C2 estimator. Furthermore, a Monte Carlo
      permutation is utilized to test reproducibility versus a zero I2C2, representing
      complete lack of reproducibility. Methodologies are applied to three replication
      studies arising from different brain imaging modalities and settings: regional
      analysis of volumes in normalized space imaging for characterizing brain
      morphology, seed-voxel brain activation maps based on resting-state functional
      magnetic resonance imaging (fMRI), and fractional anisotropy in an area
      surrounding the corpus callosum via diffusion tensor imaging. Notably, resting
      state fMRI brain activation maps are found to have low reliability, ranging from
      .2 to .4. Software and data are available to provide easy access to the proposed
      methods.

PMID- 24022793
TI  - Creativity and schizotypy from the neuroscience perspective.
AB  - Behavioral research has revealed that some cognitive features may be similar
      between creative and psychotic/schizophrenic-like thoughts. In this study, we
      addressed the potential link between creativity and schizotypy at the level of
      the brain by investigating functional patterns of brain activity (using
      functional magnetic resonance imaging) during creative cognition in preselected
      groups with low versus high psychometrically determined schizotypy. Our findings
      revealed an association between the originality component of creativity and
      reduced deactivation of right parietal brain regions and the precuneus during
      creative cognition, congruent with the idea that more-creative people may include
      many more events/stimuli in their mental processes than do less-creative people.
      Similarly, the high-schizotypy group showed weaker deactivation of the right
      precuneus during creative cognition. The fact that originality and schizotypy
      show similar functional brain activity patterns during creative ideation (i.e.,
      reduced deactivation of the right precuneus) strongly supports the contention
      that similar mental processes may be implicated in creativity and in psychosis
      proneness.

PMID- 24022794
TI  - Design-based treatment of unit nonresponse in environmental surveys using
      calibration weighting.
AB  - Unit nonresponse is often a problem in sample surveys. It arises when the values
      of the survey variable cannot be recorded for some sampled units. In this paper,
      the use of nonresponse calibration weighting to treat nonresponse is considered
      in a complete design-based framework. Nonresponse is viewed as a fixed
      characteristic of the units. The approach is suitable in environmental and forest
      surveys when sampled sites cannot be reached by field crews. Approximate
      expressions of design-based bias and variance of the calibration estimator are
      derived and design-based consistency is investigated. Choice of auxiliary
      variables to perform calibration is discussed. Sen-Yates-Grundy, Horvitz
      Thompson, and jackknife estimators of the sampling variance are proposed.
      Analytical and Monte Carlo results demonstrate the validity of the procedure when
      the relationship between survey and auxiliary variables is similar in respondent
      and nonrespondent strata. An application to a forest survey performed in
      Northeastern Italy is considered. 

PMID- 24022792
TI  - Resources required for processing ambiguous complex  features in vision and
      audition are modality specific.
AB  - Processing multiple complex features to create cohesive representations of
      objects is an essential aspect of both the visual and auditory systems. It is
      currently unclear whether these processes are entirely modality specific or
      whether there are amodal processes that contribute to complex object processing
      in both vision and audition. We investigated this using a dual-stream target
      detection task in which two concurrent streams of novel visual or auditory
      stimuli were presented. We manipulated the degree to which each stream taxed
      processing conjunctions of complex features. In two experiments, we found that
      concurrent visual tasks that both taxed conjunctive processing strongly
      interfered with each other but that concurrent auditory and visual tasks that
      both taxed conjunctive processing did not. These results suggest that resources
      for processing conjunctions of complex features within vision and audition are
      modality specific.

PMID- 24022795
TI  - New mercury-contained cationic frameworks stabilized by (GaCl4)- unit via weak
      electrostatic forces in supramolecular compounds (Hg11P4)(GaCl4)4 and
      (Hg3AsS)(GaCl4).
AB  - Two new inorganic supramolecular compounds, (Hg11P4)(GaCl4)4 (1) and
      (Hg3AsS)(GaCl4) (2), have been prepared by the solid-state reactions. Their
      structures are characterized by mercury-containing cationic hosts and discrete
      (GaCl4)(-) guests, which is a derivative of a very strong Lewis acid. The three
      dimensional cationic framework of 1, (Hg11P4)(4+), is marvellously extended by
      Hg2(2+) and Hg3(2+) groups as well as Hg(2+) ions to form two large tunnels with
      different sizes each embedded with two columns of (GaCl4)(-) anions. Compound 2
      features a layered structure with (GaCl4)(-) tetrahedra being intercalated
      between two-dimensional (Hg3AsS)(+) layers and it is the first mercury
      pnictidechalcohalide. It is found that the weak electrostatic forces between
      hosts and guests play a key role in the stabilization of the whole structures of
      1 and 2, which is strikingly different from almost all the reported metal
      pnictidehalide and chalcohalide supramolecular compounds. Optical dielectric
      constants calculations show that both 1 and 2 possess strong dielectric
      anisotropy.

PMID- 24022797
TI  - A mysterious post-traumatic pulsatile exophthalmos.

PMID- 24022798
TI  - Upside-down stomach as a rare cause of obstructive shock and cardiac arrest.

PMID- 24022796
TI  - Physicians declining patient enrollment in a critical care trial: a case study in
      thromboprophylaxis.
AB  - PURPOSE: To analyze the frequency, rationale and determinants of attending
      physicians requesting that their eligible patients not be approached for
      participation in a thromboprophylaxis trial. METHODS: Research personnel in 67
      centers prospectively documented eligible non-randomized patients due to
      physicians declining to allow their patients to be approached. RESULTS: In 67
      centers, 3,764 patients were enrolled, but 1,460 eligible patients had no consent
      encounter. For 218 (14.9 %) of these, attending physicians requested that their
      patients not be approached. The most common reasons included a high risk of
      bleeding (31.2 %) related to fear of heparin bioaccumulation in renal failure,
      the presence of an epidural catheter, peri-operative status or other factors;
      specific preferences for thromboprophylaxis (12.4 %); morbid obesity (9.6 %);
      uncertain prognosis (6.4 %); general discomfort with research (3.7 %) and unclear
      reasons (17.0 %). Physicians were more likely to decline when approached by less
      experienced research personnel; considering those with[10 years of experience as
      the reference category, the odds ratios (OR) for physician refusals to personnel
      without trial experience was 10.47 [95 % confidence interval (CI) 2.19-50.02] and
      those with less than 10 years experience was 1.72 (95 % CI 0.61-4.84). Physicians
      in open rather than closed units were more likely to decline (OR 4.26; 95 % CI
      1.27-14.34). Refusals decreased each year of enrollment compared to the pilot
      phase. CONCLUSIONS: Tracking, analyzing, interpreting and reporting the rates and
      reasons for physicians declining to allow their patients to be approached for
      enrollment provides insights into clinicians' concerns and attitudes to trials.
      This information can encourage physician communication and education, and
      potentially enhance efficient recruitment.

PMID- 24022799
TI  - Adult eyewitness memory and compliance: effects of post-event misinformation on
      memory for a negative event.
AB  - This study investigated effects of misleading post-event information, delay, and
      centrality definition on eyewitness memory and suggestibility for a negative
      event (a vividly filmed murder). Either immediately or 2 weeks after viewing the
      film, 93 adults read a (misleading or control) narrative about the event and then
      completed a recognition memory test. Misinformation acceptance was operative, but
      strong evidence for memory malleability was lacking. Compliance predicted
      misinformation effects, especially on the delayed test. Although accuracy was
      generally higher for central than peripheral information, centrality criteria
      influenced the pattern of results. Self-report of greater distress was associated
      with better recognition accuracy. The results suggest that use of different
      centrality definitions may partly explain inconsistencies across studies of
      memory and suggestibility for central and peripheral information. Moreover,
      social factors appeared, at least in part, to influence misinformation effects
      for the highly negative event, especially as memory faded. Implications for
      eyewitness memory and suggestibility are discussed.

PMID- 24022800
TI  - In vitro blood and fibroblast responses to BisGMA-TEGDMA/bioactive glass
      composite implants.
AB  - This in vitro study was designed to evaluate both blood and human gingival
      fibroblast responses to bisphenol A-glycidyl methacrylate-triethyleneglycol
      dimethacrylate (BisGMA-TEGDMA)/bioactive glass (BAG) composite, aimed to be used
      as composite implant abutment surface modifier. Three different types of
      substrates were investigated: (a) plain polymer (BisGMA 50 wt%-TEGDMA 50 wt%),
      (b) BAG-composite (50 wt% polymer + 50 wt% fraction of BAG-particles, <50 MUm),
      and (c) plain BAG plates (100 wt% BAG). The blood response, including the blood
      clotting ability and platelet adhesion morphology were evaluated. Human gingival
      fibroblasts were plated and cultured on the experimental substrates for up to 10
      days, then the cell proliferation rate was assessed using AlamarBlue assayTM. The
      BAG-composite and plain BAG substrates had a shorter clotting time than plain
      polymer substrates. Platelet activation and aggregation were most extensive,
      qualitatively, on BAG-composite. Analysis of the normalized cell proliferation
      rate on the different surfaces showed some variations throughout the experiment,
      however, by day 10 the BAG-composite substrate showed the highest (P < 0.001)
      cell proliferation rate. In conclusion, the presence of exposed BAG-particles
      enhances fibroblast and blood responses on composite surfaces in vitro.

PMID- 24022801
TI  - In vitro biocompatibility assessment of Ti40Cu38Zr10Pd12 bulk metallic glass.
AB  - The use of biocompatible materials has attained an increasing importance for
      tissue regeneration and transplantation. The excellent mechanical and corrosion
      properties of Ti40Cu38Zr10Pd12 bulk metallic glass (BMG) turn it into a potential
      candidate for its use in orthopaedic implants. Before being considered as a
      biomaterial, some biological parameters must be taken into account. In this
      study,mouse preosteoblasts were cultured in the presence or absence of the alloy
      at different times (24 h, 7 and 21 days) and no differences in cell viability
      were detected.Moreover, cells were able to adhere to the alloy surface by
      establishing focal contacts, and displayed a flattened polygonal morphology.
      After 14 days in culture, differentiation into osteoblasts was observed. Besides,
      the amount of Cu ions released and their potential toxic effects were analyzed,
      showing that the amount of Cu released did not increase cell death. Finally, the
      low levels of inflammatory cytokines secreted by THP-1 differentiated macrophages
      exposed to the alloy suggest the absence of an immunogenic response to the alloy.
      In conclusion, in vitro studies indicate that the Ti40Cu38Zr10Pd12 BMG could be
      considered as a biomaterial to be used in orthopaedic implants.

PMID- 24022802
TI  - Challenges in the management of hemophilia B with inhibitor.
AB  - Development of factor IX (FIX) inhibitor is a rare but challenging complication
      in hemophilia B. In addition to inefficacy of specific replacement therapy, FIX
      inhibitors increase morbidity due to serious allergic reactions/anaphylaxis upon
      treatment with FIX. Limited experience with immune tolerance induction (ITI)
      shows a high risk of nephrotic syndrome development and poor ITI outcomes.
      Recently, immunomodulation therapy has been used in ITI regimens in hemophilia B;
      however, relevant guidelines for ITI in hemophilia B are still lacking. We
      describe a 7-year-old hemophilia B patient with "null" mutation Arg29 stop who
      underwent surgery and massive transfusion therapy in the neonatal period and
      developed an FIX inhibitor after consecutive 20 exposures to FIX concentrate. At
      the age of 6 years, a high-dose ITI was commenced combined with immunomodulation
      therapy including rituximab, dexamethasone, and intravenous immunoglobulin.
      Allergic reactions that occurred in the third week of ITI were resolved by
      premedication with antihistamines and continued immunomodulation protocol without
      any need for ITI interruption. Inhibitor was negative from week 10; however,
      doses of FIX continued unchanged until pharmacokinetic criteria for success were
      met at month 9 of ITI. One year after the start of ITI, the patient started
      regular prophylaxis with FIX 41 IU/kg three times a week. No further allergic
      reactions or any signs of nephrotic syndrome have occurred. 

PMID- 24022803
TI  - Noninvasive assessment of liver fibrosis in patients with chronic hepatitis C
      (and congenital bleeding disorders): where do we stand?
AB  - The assessment and monitoring of liver fibrosis (LF) is a key issue in the
      management and definition of prognosis of patients with chronic hepatitis C
      (CHC). In this respect, despite recognized limitations (invasive nature, sampling
      errors, interobserver variability, nondynamic evaluation of LF), liver biopsy is
      traditionally considered the reference standard. These limitations stimulated the
      search for noninvasive approaches for the assessment of LF, particularly
      attractive in patients with hemophilia and other congenital bleeding disorders
      (CBD). In patients with congenital bleeding disorders (CBD), who often suffer
      from CHC because of the past use of nonvirally inactivated plasma-derived
      products, the risk of bleeding hamper to routinely obtain histological data for
      LF staging. A variety of methods have been proposed and, in some cases, validated
      in patients with CHC and other liver diseases, including biomarkers directly or
      indirectly associated with LF, often combined in scores or algorithms, and the
      more recently developed physical approaches, evaluating the properties of the
      liver parenchyma with instrumental techniques studying the propagation of
      specific signals, that is, transient elastography (TE), acoustic radiation force
      impulse imaging elastography, and magnetic resonance elastography. This review
      will describe the available strategies for noninvasive assessment of LF, with
      more details on the latter promising instrumental approaches. Moreover, although
      lacking of validation against liver biopsy, recent studies extending the use of
      noninvasive methods (particularly TE) in the setting of patients with CBD will be
      discussed. 

PMID- 24022804
TI  - Arthropathy in patients with moderate hemophilia a: a systematic review of the
      literature.
AB  - Chronic arthropathy is a major complication in severe hemophilia A (Factor [F]
      VIII < 1%). Almost all adults with severe hemophilia, who have not received
      prophylaxis with FVIII since their early childhood, suffer from chronic
      arthropathy. Patients with moderate hemophilia (FVIII activity 1-5%) usually
      experience fewer joint bleeds than those with severe hemophilia and are thought
      to rarely develop a significant degree of chronic arthropathy. However, some
      patients with moderate hemophilia behave like those with the severe form of the
      disorder, reporting several joint bleeds per year and significant joint
      impairment. Currently, only little data are available about the prevalence of
      arthropathy, the degree of quality of life impairment, and the need for
      orthopedic care/aids in patients with moderate hemophilia. In this systematic
      review of literature, the prevalence of overt arthropathy ranges between 15 and
      77% in patients with moderate hemophilia and prophylactic replacement treatment
      is prescribed in approximately 30% of these patients, usually after diagnosis of
      clinically overt arthropathy. Moreover, because of the lack of imaging studies
      (magnetic resonance and/or ultrasound), the prevalence of subclinical arthropathy
      cannot be determined. These data confirm that severity of hemophilia should not
      be defined only according to FVIII levels and that a relevant proportion of
      patients with nonsevere hemophilia might benefit from a "tailored early
      prophylaxis." 

PMID- 24022805
TI  - Clinical judgment when using coagulation tests during direct oral anticoagulant
      treatment: a concise review.
AB  - Because their anticoagulant effect is dose predictable, steady, and little
      influenced by diet and drugs, laboratory monitoring was deemed unnecessary in
      trials on venous and arterial thromboprophylaxis with the direct oral
      anticoagulant drugs (DOACs) rivaroxaban, apixaban, edoxaban, or dabigatran.
      However, there are special clinical settings in which measurement of their
      anticoagulant effect may be clinically desired. Because of lack of
      standardization between reagents employed and their global nature, the activated
      partial thromboplastin time (APTT) and the prothrombin time (PT) are not
      generally suitable for accurately assessing the anticoagulant effect of DOACs.
      The modified (diluted) PT reliably quantifies the anticoagulant effect of
      rivaroxaban or of apixaban. However, a higher intraindividual variability from
      one PT reagent to another is found when the data are compared with those obtained
      with standard PT. The HEMOCLOT (HYPHEN BioMed, France) assay is a modified
      (diluted) thrombin time (TT) provided with dabigatran calibrators. However, it is
      performed only in few specialized centers. Anti-factor Xa (anti-FXa) chromogenic
      assays employ routine automated coagulometers or manual spectrometers, and kits
      for anti-FIIa assays that measure dabigatran levels and kits for anti-Xa with
      rivaroxaban calibrators are commercially available. However, no correlation has
      been identified between any of these tests and clinical outcomes in patients
      taking any of the DOACs. Thus, currently, there are evidence gaps regarding the
      role of laboratory testing for surveillance and management of adverse events
      associated with DOACs. In view of this, in addition to standardization,
      validation of such assays is mandatory before they can be used to make clinical
      decisions. 

PMID- 24022806
TI  - Systematic review of the role of FVIII concentrates in inhibitor development in
      previously untreated patients with severe hemophilia a: a 2013 update.
AB  - Nowadays, patients with hemophilia A receive a high standard of care; therefore,
      the most challenging complication of factor VIII (FVIII) replacement therapy has
      become the development of FVIII inhibitors, which render the concentrate infusion
      ineffective and expose patients to an increased risk of morbidity and mortality.
      Among environmental risk factors influencing inhibitor development, the type of
      FVIII products has always drawn the attention of investigators. Conflicting
      results are reported in the literature concerning rates of inhibitor development
      after either plasma-derived or recombinant FVIII concentrates. To help elucidate
      this controversial issue, we have performed a systematic review and meta-analysis
      of prospective studies evaluating the incidence of inhibitors in previously
      untreated patients with severe hemophilia A receiving plasma-derived or
      recombinant FVIII products. The quality of the studies was assessed using the
      Newcastle-Ottawa Scale (NOS), the STrenghtening the Reporting of OBservational
      studies in Epidemiology and an ad hoc quality score. Overall, 28 prospective
      studies, including 1,421 patients with hemophilia A, fulfilled our selection
      criteria and were included in the systematic review. No statistically significant
      differences were observed in the inhibitor incidence between plasma-derived and
      recombinant FVIII concentrates considering all (weighted means: 23%, 95% CI: 15
      33% vs. 29%, 95% CI: 26-32%) and high titer (16%, 95% CI: 10-26% vs. 18%, 95% CI:
      15-21%) inhibitors. Similarly, no significant differences were found in the
      inhibitor incidence among the different classes of recombinant products. In
      conclusion, the results of our meta-analysis show that the different types of
      FVIII products are not associated with different risks of inhibitor development. 

PMID- 24022807
TI  - Influence of residual platelet count on routine coagulation, factor VIII, and
      factor IX testing in postfreeze-thaw samples.
AB  - The use of frozen-thawed samples rather than fresh samples for specialized
      coagulation testing is becoming commonplace, thereby creating novel risks that
      may jeopardize the quality of hemostasis testing. Residual platelets (PLTs) in
      frozen plasma are most critical as freezing-induced activation and injury may
      impair routine and specialized testing after thawing. The aim of this study was
      to verify the impact of postcentrifugation PLT count in postfreeze-thawed samples
      on activated partial thromboplastin time (APTT), prothrombin time (PT),
      fibrinogen, factor VIII (FVIII) activity testing, and factor IX (FIX) activity
      testing. These parameters were herein assessed in postfreeze-thaw paired plasma
      samples collected from 15 healthy volunteers and subjected to 4 different
      centrifugation forces (i.e., 3,000, 1,500, 1,000, and 500g), using data obtained
      with centrifugation force of 1,500g as the gold standard, in agreement with
      current recommendations. Compared with reference samples, PLT counts in fresh
      aliquots were indistinguishable in specimens centrifuged at 1,000g, significantly
      lower in those centrifuged at 3,000g and significantly higher in those
      centrifuged at 500g. In all cases except samples centrifuged at 3,000g, the PLT
      count was significantly decreased in postfreeze-thaw compared with paired fresh
      specimens. In postfreeze-thaw plasma, APTT was not influenced by residual PLT
      count. The results of PT and fibrinogen were consistently altered in samples
      centrifuged at 1,000 and 500g, though the correlation with the reference measures
      remained clinically acceptable. Data obtained for FVIII and FIX activities
      revealed a positive bias in all postfreeze-thaw plasmas, achieving statistical
      significance in samples centrifuged at 3,000g. We conclude that alteration of
      centrifuge speeds away from the recommended 1,500g may influence the level of
      residual PLTs in sample centrifuged at lower speeds such as 500g, and therefore
      may make these specimens unsuitable for hemostasis testing in postfreeze-thawed
      plasma samples. In addition, although the changes seen in FVIII and FIX in
      samples centrifuged at 3,000g may reflect non-PLT-related effects, such changes
      should also be considered in this setting. 

PMID- 24022808
TI  - Tailored versus standard dose prophylaxis in children with hemophilia A.
AB  - Prophylaxis is universally recognized as the treatment of choice in people with
      hemophilia, and tailored prophylaxis is the consistent modification of the
      standard weight-based dosing regimen. A large number of factors guide the choice
      of a specific tailored regimen, and different regimens are under evaluation.
      Tailored low-dose frequent regimens are likely to be cost-effective, but they are
      less accepted by patients. Escalating dose regimens seem to be quite effective in
      preventing bleedings and, consequently, arthropathy, although data on long-term
      outcomes are still not available. Pharmacokinetic-driven approaches have been
      also proposed. Sensitive and validated tools able to reliably measure the
      different outcomes are necessary in this setting. With regard to the evaluation
      of arthropathy, magnetic resonance imaging and ultrasound are promising imaging
      techniques in detecting early joint damage. Factor VIII trough levels can be
      considered a measure of the efficacy of FVIII infused, although other factors
      influence the bleeding pattern. Global assays of coagulation could provide more
      complete information on the hemostatic potential of a sample and predict bleeding
      phenotype. These techniques are also promising for the individualization of
      prophylaxis regimens, potentially resulting in less frequent dosing, more
      comfortable and less expensive approaches. 

PMID- 24022810
TI  - Development of singlet oxygen-responsive phosphorescent ruthenium(II) complexes.
AB  - By using an anthryl-substituted 2,2'-bipyridine as a singlet oxygen-reactive
      ligand, a new class of Ru(II)-bipyridine complex derivatives that can
      specifically respond to singlet oxygen with remarkable phosphorescence
      enhancements have been successfully developed.

PMID- 24022811
TI  - Evidence for self-maintaining pluripotent murine stem cells  in embryoid bodies.
AB  - Pluripotent stem cells have great potential for regenerative medicine; however,
      their clinical use is associated with a risk of tumor formation. We utilized
      pluripotent cells expressing green fluorescent protein and puromycin resistance
      under control of the Oct4 promoter to study the persistence of potential
      pluripotent cells under embryoid body (EB) culture conditions, which are commonly
      used to obtain organotypic cells. We found that i.) OCT4-expressing cells
      dramatically decrease during the first week of differentiation, ii.) the number
      of OCT4-expressing cells recovers from day 7 on, iii.) the OCT4-expressing cells
      are similar to embryonic stem cells grown in the presence of leukemia inhibitory
      factor LIF but express several markers associated with germ cell formation, such
      as DAZL and STRA-8 and iv.) the persistence of potentially pluripotent cells is
      independent of supportive cells in EBs. Finally, OCT4-expressing cells, isolated
      from EBs after 2-month of culture, were further maintained under feeder-free
      conditions in absence of LIF and continued to express OCT4 in 95 % of the
      population for at least 36 days. These findings point to an alternative state of
      stable OCT4 expression. In the frame of the landscape model of differentiation
      two attractors of pluripotency might be defined based on their different
      characteristics.

PMID- 24022812
TI  - Nutritional properties of einkorn wheat (Triticum monococcum L.).
AB  - The hulled wheat einkorn (Triticum monococcum L. ssp. monococcum), a staple food
      of early farmers for many thousand years, today is cropped only in small areas of
      the Mediterranean region and continental Europe. Increasing attention to the
      nutritional quality of foods has fostered renewed interest in this low-impact
      crop. The reappraisal of einkorn quality evidenced that this ancient wheat has
      some dietary advantages over polyploid wheats. Einkorn wholemeal is poor in
      dietary fibre but rich in proteins, lipids (mostly unsaturated fatty acids),
      fructans and trace elements (including zinc and iron). The good concentration of
      several antioxidant compounds (carotenoids, tocols, conjugated polyphenols,
      alkylresorcinols and phytosterols) and low beta-amylase and lipoxygenase
      activities (which limit antioxidant degradation during food processing)
      contribute to the excellent nutritional properties of its flour, superior to
      those of other wheats. Conversely, einkorn has relatively low bound polyphenol
      content and high polyphenol oxidase activity. In spite of eliciting weaker toxic
      reactions than other Triticum species, einkorn is not suitable for coeliacs.
      Current trends towards the consumption of functional foods suggest that this
      cereal may still play a significant role in human consumption, especially in the
      development of new or special foods with superior nutritional quality.

PMID- 24022813
TI  - Validation of healthcare administrative data for the diagnosis of epilepsy.
AB  - BACKGROUND: Administrative databases have become an important tool to monitor
      diseases. Patients with epilepsy could be traced using disease-specific codes and
      prescriptions, but formal validation is required to obtain an accurate case
      definition. The aim of the study was to correlate administrative data on epilepsy
      with an independent source of patients with epilepsy in a district of Lombardy,
      Northern Italy, from 2000 to 2008. METHODS: Data of nearly 320 600 inhabitants in
      the district of Lecco collected from the Drug Administrative Database of the
      Lombardy Region were analysed. Among them were included patients who fulfilled
      the International Classification of Diseases 9 (ICD-9) codes and/or the disease
      specific exemption code for epilepsy and those who had at least one EEG record
      and took antiepileptic drugs (AEDs) as monotherapy or in variable combinations.
      To ascertain epilepsy cases, 11 general practitioners (GPs) with 15 728
      affiliates were contacted. Multiple versions of the diagnostic algorithm were
      developed using different logistic regression models and all combinations of the
      four independent variables. RESULTS: Among the GP affiliates, 71 (4.5/1000) had a
      gold standard diagnosis of epilepsy. The best and most conservative algorithm
      included EEG and selected treatment schedules and identified 61/71 patients with
      epilepsy (sensitivity 85.9%, CI 76.0% to 92.2%) and 15 623/15 657 patients
      without epilepsy (specificity 99.8%,CI 99.7% to 99.8%). The positive and negative
      predictive values were 64.2% and 99.9%. Sensitivity (86.7%) and the positive
      predictive value (68.4%) increased only slightly when patients with single
      seizures were included. CONCLUSIONS: A diagnostic algorithm including EEG and
      selected treatment schedules is only moderately sensitive for the detection of
      epilepsy and seizures. These findings apply only to the Northern Italian
      scenario.

PMID- 24022814
TI  - The prospective association between childhood cognitive ability and somatic
      symptoms and syndromes in adulthood: the 1958 British birth cohort.
AB  - BACKGROUND: Cognitive ability is negatively associated with functional somatic
      symptoms (FSS) in childhood. Lower childhood cognitive ability might also predict
      FSS and functional somatic syndromes in adulthood. However, it is unknown whether
      this association would be modified by subjective and objective measures of
      parental academic expectations. METHODS: 14 068 participants from the 1958
      British birth cohort, whose cognitive ability was assessed at 11 years. Outcomes
      were somatic symptoms at 23, 33 and 42 years. Self-reported irritable bowel
      syndrome (IBS), chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and
      operationally defined CFS-like illness were measured at 42 years. RESULTS: Lower
      cognitive ability at age 11 years was associated with somatic symptoms at ages
      23, 33 and 42 years. Adjusting for sex, childhood internalising problems,
      previous somatic symptoms and concurrent psychological symptoms, childhood
      cognitive ability remained negatively associated with somatic symptoms at age 23
      years (beta=-0.060, 95% CI -0.081 to -0.039, p<0.01), 33 years (beta = -0.031,
      95% CI -0.050 to -0.011, p<0.01), but not with somatic symptoms at 42 years.
      Overall, we found no clear association between lower childhood cognitive ability
      and CFS/ME, CFS-like illness and IBS. Associations between cognitive ability and
      somatic symptoms at 23 years were moderated by low parental social class, but not
      by subjective indicators of parental academic expectations. CONCLUSIONS: Lower
      childhood cognitive ability predicted somatic symptoms, but not CFS/ME, CFS-like
      illness and IBS in adulthood. While earlier research indicated an important role
      for high parental academic expectations in the development of early-life FSS,
      these expectations do not seem relevant for somatic symptoms or functional
      somatic syndromes in later adulthood.

PMID- 24022815
TI  - Ambient air pollution and hypertensive disorder of pregnancy.
AB  - BACKGROUND: Ambient air pollution has been implicated in the development of
      hypertensive disorders of pregnancy (HDP). However, evidence of the association
      between air pollution and HDP is still limited, and the effects of gaseous air
      pollutants on HDP and their time windows of exposure have not been well studied.
      METHODS: We used the Florida birth registry data to investigate the associations
      between air pollutants (NO2, SO2, PM(2.5), O3 and CO) and the risks of HDP in
      22,041 pregnant women in Jacksonville, Florida, USA from 2004 to 2005. Further,
      we examined whether air pollution exposure during different time windows defined
      by trimesters and the entire pregnancy had different effects on HDP. RESULTS: The
      single-pollutant logistic regression model showed that exposure to four
      pollutants during the full pregnancy period was significantly associated with
      prevalence of HDP after adjusting for covariates: NO2 (OR=1.21, 95% CI 1.09 to
      1.35), PM2.5 (OR=1.24, 95% CI 1.08 to 1.43), SO2 (OR=1.13, 95% CI 1.01 to 1.25)
      and CO (OR=1.12, 95% CI 1.03 to 1.22) per IQR increase. Similar effects were
      observed when first trimester exposure to NO2, SO2 and CO, and second trimester
      exposures to PM2.5 were examined. Consistent results were confirmed in multiple
      pollutant models. CONCLUSIONS: This study suggests that exposure to high levels
      of air pollution during early pregnancy and the full gestational period was
      associated with increased prevalence of HDP in Florida, USA.

PMID- 24022816
TI  - Process evaluation in complex public health intervention studies: the need for
      guidance.

PMID- 24022818
TI  - The effects of high concentrations of vitamin C on cancer cells.
AB  - The effect of high doses of vitamin C for the treatment of cancer has been
      controversial. Our previous studies, and studies by others, have reported that
      vitamin C at concentrations of 0.25-1.0 mM induced a dose- and time-dependent
      inhibition of proliferation in acute myeloid leukemia (AML) cell lines and in
      leukemic cells from peripheral blood specimens obtained from patients with AML.
      Treatment of cells with high doses of vitamin C resulted in an immediate increase
      in intracellular total glutathione content and glutathione-S transferase activity
      that was accompanied by the uptake of cysteine. These results suggest a new role
      for high concentrations of vitamin C in modulation of intracellular sulfur
      containing compounds, such as glutathione and cysteine. This review, discussing
      biochemical pharmacologic studies, including pharmacogenomic and
      pharmacoproteomic studies, presents the different pharmacological effects of
      vitamin C currently under investigation. 

PMID- 24022817
TI  - The metabolic burden of methyl donor deficiency with focus on the betaine
      homocysteine methyltransferase pathway.
AB  - Methyl groups are important for numerous cellular functions such as DNA
      methylation, phosphatidylcholine synthesis, and protein synthesis. The methyl
      group can directly be delivered by dietary methyl donors, including methionine,
      folate, betaine, and choline. The liver and the muscles appear to be the major
      organs for methyl group metabolism. Choline can be synthesized from
      phosphatidylcholine via the cytidine-diphosphate (CDP) pathway. Low dietary
      choline loweres methionine formation and causes a marked increase in S
      adenosylmethionine utilization in the liver. The link between choline, betaine,
      and energy metabolism in humans indicates novel functions for these nutrients.
      This function appears to goes beyond the role of the nutrients in gene
      methylation and epigenetic control. Studies that simulated methyl-deficient diets
      reported disturbances in energy metabolism and protein synthesis in the liver,
      fatty liver, or muscle disorders. Changes in plasma concentrations of total
      homocysteine (tHcy) reflect one aspect of the metabolic consequences of methyl
      group deficiency or nutrient supplementations. Folic acid supplementation spares
      betaine as a methyl donor. Betaine is a significant determinant of plasma tHcy,
      particularly in case of folate deficiency, methionine load, or alcohol
      consumption. Betaine supplementation has a lowering effect on post-methionine
      load tHcy. Hypomethylation and tHcy elevation can be attenuated when choline or
      betaine is available. 

PMID- 24022819
TI  - Pediatric melanoma: analysis of an international registry.
AB  - BACKGROUND: The management of pediatric melanoma (PM) has largely been
      extrapolated from adult data. However, the behavior of PM appears to differ from
      its adult counterparts. Therefore, an international PM registry was created and
      analyzed. METHODS: Twelve institutions contributed deidentified clinicopathologic
      and outcome data for patients diagnosed with PM from 1953 through 2008. RESULTS:
      Overall survival (OS) data were reported for 365 patients with invasive PM who
      had adequate follow-up data. The mean age of the patients was 16 years (range 1
      year-21 years). The 10-year OS rate, 80.6%, tended to vary by patient age: 100%
      for those aged birth to 10 years, 69.7% for those aged > 10 years to 15 years,
      and 79.5% for those aged > 15 years to 20 years (P = .147). Patients with
      melanomas measuring <= 1 mm had a favorable prognosis (10-year OS rate of 97%),
      whereas survival was lower but similar for patients with melanomas measuring > 1
      mm to 2 mm, > 2 mm to 4 mm, and > 4 mm (70%, 78%, and 80%, respectively; P =
      .0077). Ulceration and lymph node metastasis were found to be correlated with
      worse survival (P = .022 and P = .017, respectively). The 10-year OS rate was
      94.1% for patients with American Joint Committee on Cancer stage I disease, 79.6%
      for those with stage II disease, and 77.1% for patients with stage III disease (P
      < .001). CONCLUSIONS: Tumor thickness, ulceration, lymph node status, and stage
      were found to be significant predictors of survival in patients with PM, similar
      to adult melanoma. There is a trend toward increased survival in children aged <=
      10 years versus adolescents aged > 10 years. Further analyses are needed to probe
      for potential biological and behavioral differences in pediatric versus adult
      melanoma.

PMID- 24022820
TI  - Evidence behind quality of care measures for venous thromboembolism and atrial
      fibrillation.
AB  - Stroke and venous thromboembolism (VTE) are serious and preventable thrombotic
      events in patients with atrial fibrillation (AF) and who undergo surgery or
      hospitalization, respectively. Nevertheless, thromboprophylaxis remains greatly
      underused. The National Quality Forum, the Agency for Healthcare Research and
      Quality, and the Joint Commission have developed quality measures aimed at
      improving the provision of appropriate thromboprophylaxis. Reporting of these
      measures will increasingly become mandatory and hospitals will face financial
      penalties for failure to report. The approval of new oral anticoagulants (direct
      thrombin and factor Xa inhibitors) may simplify provision of thromboprophylaxis
      and eventually increase adherence to guidelines and quality measures. The primary
      objective of this review is to present evidence supporting the core quality
      measures for VTE prevention and stroke prevention in patients with AF. The
      secondary objective is to familiarize physicians with the new anticoagulants and
      their approved indications. This review concludes with a brief description of the
      Society of Hospital Medicine online resources for VTE prevention as well as
      recommendations for planning and implementation of quality improvement in the
      management of VTE. 

PMID- 24022821
TI  - Use of an extracorporeal circulation perfusion simulator: evaluation of its
      accuracy and repeatability.
AB  - Medical simulators have mainly been used as educational tools. They have been
      used to train technicians and to educate potential users about safety. We
      combined software for hybrid-type extracorporeal circulation simulation (ECCSIM)
      with a CPB-Workshop console. We evaluated the performance of ECCSIM, including
      its accuracy and repeatability, during simulated ECC. We performed a detailed
      evaluation of the synchronization of the software with the console and the
      function of the built-in valves. An S-III heart-lung machine was used for the
      open circuit. It included a venous reservoir, an oxygenator (RX-25), and an
      arterial filter. The tubes for venous drainage and the arterial line were
      connected directly to the ports of the console. The ECCSIM recorded the liquid
      level of the reservoir continuously. The valve in the console controlled the
      pressure load of the arterial line. The software made any adjustments necessary
      to both arterial pressure load and the venous drainage flow volume. No external
      flowmeters were necessary during simulation. We found the CPB-Workshop to be
      convenient, reliable, and sufficiently exact. It can be used to validate
      procedures by monitoring the controls and responses by using a combination of
      qualitative measures.

PMID- 24022823
TI  - Role of interleukin-10 in endochondral bone formation in mice: anabolic effect
      via the bone morphogenetic protein/Smad pathway.
AB  - OBJECTIVE: Interleukin-10 (IL-10) is a pleiotropic immunoregulatory cytokine with
      a chondroprotective effect that is elevated in cartilage and synovium in patients
      with osteoarthritis. However, the role of IL-10 during endochondral bone
      formation and its mechanism of action have not been elucidated. METHODS: IL-10(-/
      ) mice and IL-10-treated tibial organ cultures were used to study loss and gain
      of IL-10 functions, respectively, during endochondral bone formation. Primary
      chondrocytes from the long bones of mouse embryos were cultured with and without
      IL-10. To assess the role of IL-10 in chondrogenic differentiation, we conducted
      mesenchymal cell micromass cultures. RESULTS: The lengths of whole skeletons from
      IL-10(-/-) mice were similar to those of their wild-type littermates, although
      their skull diameters were smaller. The tibial growth plates of IL-10(-/-) mice
      showed shortening of the proliferating zone. Treatment with IL-10 significantly
      increased tibial lengths in organ culture. IL-10 also induced chondrocyte
      proliferation and hypertrophic differentiation in primary chondrocytes in vitro.
      Mechanistically, IL-10 activated STAT-3 and the Smad1/5/8 and ERK-1/2 MAP kinase
      pathways and induced the expression of bone morphogenetic protein 2 (BMP-2) and
      BMP-6 in primary chondrocytes. Furthermore, the blocking of BMP signaling
      attenuated the IL-10-mediated induction of cyclin D1 and RUNX-2 in primary
      chondrocytes and suppressed Alcian blue and alkaline phosphatase staining in
      mesenchymal cell micromass cultures. CONCLUSION: These results indicate that IL
      10 acts as a stimulator of chondrocyte proliferation and chondrogenic or
      hypertrophic differentiation via activation of the BMP signaling pathway.

PMID- 24022824
TI  - Improved solubility of DNA in recyclable and reusable bio-based deep eutectic
      solvents with long-term structural and chemical stability.
AB  - The solubility of DNA in bio-based deep eutectic solvents (DESs) consisting of
      mixtures of choline chloride with levulinic acid, glycerol, ethylene glycol,
      sorbitol and resorcinol was investigated. The macromolecule was found to be
      soluble and chemically and structurally stable in DESs consisting of mixtures
      containing glycerol and ethylene glycol. Furthermore recyclability of the DESs
      was demonstrated over three consecutive reuses in DNA dissolution. 

PMID- 24022825
TI  - Identity categories and transformational paths for face changes across the age
      spectrum.
AB  - How faces change across lengthy time periods and whether the changing appearance
      of a face functions as an identity category was investigated in two experiments.
      In Experiment 1, the faces of 15 individuals were multidimensionally scaled at
      each of seven age epochs (roughly <6 months to 75 years of age) and correlated
      with the same persons, but at different ages. In Experiment 2, three individuals
      at each of seven age epochs were multidimensionally scaled, and analyses explored
      the conceptual structure and transformational path of each person within the
      space. The results revealed that even the earliest age epochs (<6 months) were
      correlated with the later epochs, except for the most extreme age, with the
      correlation highest at intermediate ages. Transformational paths were found that
      emerged and terminated at haphazard points in the space. Results are discussed in
      terms of principled change in categories whose members systematically change
      across their life cycle, including suggestions for the need to incorporate
      systematic change in current theories of categorization.

PMID- 24022826
TI  - Relationship between muscle fatty infiltration and the biological characteristics
      and stimulation potential of tenocytes from rotator cuff tears.
AB  - The healing after rotator cuff surgery is still dissatisfying, and increased
      muscle fatty infiltration even more impairs the healing success. To achieve
      sufficient healing after rotator cuff reconstructions, the use of growth factors
      may be one possibility. The aim of the study was to identify a possible
      relationship between fatty infiltration of the supraspinatus muscle and cellular
      biological characteristics and stimulation potential of tenocyte-like cells
      (TLCs). TLCs of 3 donor groups differing in grade of muscle fatty infiltration
      were analyzed for their cellular characteristics and were stimulated with BMP-2
      or BMP-7 in a 3D scaffold culture. The cell count and potency for self-renewal
      were significantly decreased in TLCs from donors with high muscle fatty
      infiltration compared to the lower fatty infiltration groups. Cell count and
      collagen-I expression as well as protein synthesis were stimulated by growth
      factors. Interestingly, TLCs of the high fatty infiltration group exhibited a
      weaker stimulation potential compared to the other groups. TLCs from donors with
      high muscle fatty infiltration generally revealed inferior characteristics
      compared to cells of lower fatty infiltration groups, which may be one reason for
      a weaker healing potential and may represent a possible starting point for the
      development of future treatment options.

PMID- 24022827
TI  - Is pediatric melanoma always malignant?

PMID- 24022829
TI  - Social economic costs and health-related quality of life in patients with
      systemic sclerosis in Spain.
AB  - OBJECTIVE: Cost-of-illness analysis is the main method of providing an overall
      vision of the economic impact of a disease. Such studies have been used to set
      priorities for health care policies and inform resource allocation. The aim of
      this study was to determine the economic burden from a societal perspective and
      health-related quality of life (HRQOL) of patients with systemic sclerosis (SSc;
      scleroderma) in Spain. METHODS: We conducted a cross-sectional, retrospective
      study of 147 patients with SSc. Data on demographic characteristics, health
      resource utilization, informal care, labor productivity losses, and HRQOL were
      collected from the questionnaires completed by patients or their caregivers.
      HRQOL was measured with the EuroQol 5-domain (EQ-5D) questionnaire. RESULTS: The
      average annual cost for an SSc patient was 21,042; the reference year for unit
      prices was 2011. Direct health care costs amounted to 8,235, direct non-health
      care costs were 5,503, and loss of labor productivity was 7,303. The largest
      expenditures were early retirement, informal care, and medication. There are
      sharp differences in the estimated cost according to the Barthel Index score
      observed. The mean EQ-5D score for SSc patients was 0.68 and the mean EQ-5D
      visual analog scale score was 64. CONCLUSION: The main strengths of this study
      lie in our bottom-up approach to costing and in the evaluation of SSc patients
      from a broad perspective (societal costs). This type of analysis is very scarce
      in international literature for rare diseases in comparison with other illnesses.
      We conclude that SSc patients incur considerable societal costs and experience
      substantial deterioration in HRQOL.

PMID- 24022828
TI  - Early gallbladder carcinoma has a favorable outcome but Rokitansky-Aschoff sinus
      involvement is an adverse prognostic factor.
AB  - The general impression about gallbladder carcinomas is that they are uniformly
      fatal; however, for the early forms, an entirely different picture indicating a
      very good prognosis is evolving from the high-incidence regions. We subjected 190
      early gallbladder carcinomas (EGBC), defined as carcinomas confined to and above
      the tunica muscularis (AJCC's Tis, T1a, and T1b), and identified in
      cholecystectomy specimens sampled entirely according to an established protocol,
      to detailed analysis. Average patient age was 57.9 years (29-95). In more than
      half of the cases (114/190; 60%), the tumor was inapparent by gross examination.
      In 81 cases (42.6%), carcinomatous epithelium abutted the muscularis, whereas
      57.4 % (n = 109) were qualified as intramucosal with no overt contiguity with
      muscularis.Intraepithelial extension into Rokitansky-Aschoff sinuses (RAS) was
      found in 34 cases (17.8 %). At the time of data analysis, 171 patients (90 %)
      [corrected] were alive. Overall actuarial survival was 92.3 % at 5 years and 90.4
      % at 10 years. The 5- and 10-year actuarial survival rates of the intramucosal
      group (93.2 and 92.1%, respectively) were not statistically different from that
      of the muscle-abutting group (89.7% and 88.2% ; p = 0.334). Patients with RAS
      involvement had a significantly shorter survival than those without (p < 0.001).
      Of the 33 patients with RAS involvement, 13 (39%) died of disease, whereas only 6
      of the 154 patients (4%) without RAS involvement died of disease. Disease-related
      mortality in these cases occurred relatively late (median 48 months). EGBC has a
      very good prognosis with a 90% 10-year survival rate. It is seen on average in
      patients almost a decade younger than those with advanced cancers. RAS
      involvement is an independent prognostic factor, and additional surgery may have
      to be considered for such cases. Occasional recurrences are encountered several
      years later, which suggests a field-effect phenomenon and warrants long-term
      follow-up.

PMID- 24022831
TI  - [W(CN)6(L)](1-/2-) (L = bidentate ligand) as a useful building unit to construct
      molecule-based magnetic systems.
AB  - Metal ions heavier than the 3d metals have attracted increasing attention due to
      their strong magnetic exchange coupling, arising from the diffuse nature of the
      extended valence orbitals of the 4d and 5d elements and the involvement of a
      large magnetic anisotropy contingent on their strong spin-orbit coupling.
      [W(CN)6(L)](1-/2-) (L = 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen))
      serves as a suitable building block for constructing molecule-based magnetic
      systems. Discrete molecular entities and one-dimensional chains are preferably
      obtained when the restricted paramagnetic precursor [W(CN)6(bpy)](-) encounters
      metal counterparts with the available coordination sites. The bimetallic magnetic
      assemblies exhibit a variety of magnetic features, along with a magnetostructural
      correlation. These include slow relaxation of magnetization, typical for single
      molecule magnets and single-chain magnets, spin-canting, and metamagnetism. The
      two-dimensional structure is stabilized by using the reduced [W(CN)6(bpy)](2-)
      complex. In this perspective article, detailed discussions of molecular materials
      based on the W(V) ion are reviewed.

PMID- 24022830
TI  - Long-term outcome call into question the benefit of positive fluid balance and
      colloid treatment after aneurysmal subarachnoid hemorrhage.

PMID- 24022832
TI  - A simple and effective method for differentiating GFP and YFP by flow cytometry
      using the violet laser.

PMID- 24022833
TI  - Husbandry, working practices and field performance  when using draught oxen in
      land preparation in Shambat,  Nile Valley, Sudan.
AB  - Little quantitative information is available on animal power in the Nile Valley
      in Sudan, despite that it is being used in the area for centuries and playing an
      important role in agriculture in the present day. A survey was conducted to
      assess draught oxen management and its association with field capacity and
      efficiency at the farm level and to identify potential areas for intervention. A
      sample of 50 farmers was selected for this purpose using the systematic random
      sampling technique. The main management parameters discussed were animal health,
      feeding, housing, work strategy and care for yoke and plough. The results showed
      that most of the farmers poorly manage their animals, and this was reflected in
      low working speeds and field efficiencies. The main dimensions of poor management
      were in veterinary care (78 % did not take their animals to the veterinary
      centre), feeding (66 % feed their animals shortly before work) and care for yoke
      (80 % did not follow daily care measures for their yokes) and plough (74 % did
      not follow plough care measure before and after work). Low working speeds (0.90
      2.0 km/h) were recorded by the majority of the farmers (64 %). The majority of
      the farmers (70 %) recorded field capacities between 0.06 and 0.10 ha/h, while
      all of them worked at high field efficiencies of >86 %. The only parameter that
      significantly affected field capacity was the yoke-related wounds (p = 0.019).
      Extension advice and capacity building in husbandry and working practices were
      identified as principal entry points for intervention.

PMID- 24022834
TI  - EZ-ASSIGN, a program for exhaustive NMR chemical shift assignments of large
      proteins from complete or incomplete triple-resonance data.
AB  - For several of the proteins in the BioMagResBank larger than 200 residues, 60 %
      or fewer of the backbone resonances were assigned. But how reliable are those
      assignments? In contrast to complete assignments, where it is possible to check
      whether every triple-resonance Generalized Spin System (GSS) is assigned once and
      only once, with incomplete data one should compare all possible assignments and
      pick the best one. But that is not feasible: For example, for 200 residues and an
      incomplete set of 100 GSS, there are 1.6 * 10260 possible assignments. In "EZ
      ASSIGN", the protein sequence is divided in smaller unique fragments. Combined
      with intelligent search approaches, an exhaustive comparison of all possible
      assignments is now feasible using a laptop computer. The program was tested with
      experimental data of a 388-residue domain of the Hsp70 chaperone protein DnaK and
      for a 351-residue domain of a type III secretion ATPase. EZ-ASSIGN reproduced the
      hand assignments. It did slightly better than the computer program PINE (Bahrami
      et al. in PLoS Comput Biol 5(3):e1000307, 2009) and significantly outperformed
      SAGA (Crippen et al. in J Biomol NMR 46:281-298, 2010), AUTOASSIGN (Zimmerman et
      al. in J Mol Biol 269:592-610, 1997), and IBIS (Hyberts and Wagner in J Biomol
      NMR 26:335-344, 2003). Next, EZ-ASSIGN was used to investigate how well NMR data
      of decreasing completeness can be assigned. We found that the program could
      confidently assign fragments in very incomplete data. Here, EZ-ASSIGN
      dramatically outperformed all the other assignment programs tested.

PMID- 24022835
TI  - Image analysis method to quantify the effect of different treatments on the
      visual meat/shell ratio of half-shelled green lipped mussels (Perna canaliculus).
AB  - BACKGROUND: Aquacultured green lipped mussel (Perna canaliculus) is the New
      Zealand export leader of seafood in terms of weight. Different treatments shrink
      mussel meat differently and affect the consumer perception of half-shelled
      mussels. In order to quantify this, digital images of half-shelled green lipped
      mussels subjected to two postharvest treatments (ultrahigh pressure (UHP) and
      heat treatment (HT)) and raw controls were taken. The ratio of the view area of
      the meat to that of the shell (labelled as 'visual condition index' (VCI)) was
      measured using image analysis. A polygonal region of interest was defined on the
      image to depict the boundary of the meat and to calculate the view area. RESULTS:
      Raw mussels had a VCI of 85%. HT mussels had a much reduced VCI of 41%,
      indicating shrinkage of the meat due to heat. UHP treatment used as a shucking
      method resulted in a VCI of 83%. Since VCI is one measure of quality for the
      consumer, this quantitative method can be used in the optimization of shucking
      treatment (HT or UHP). CONCLUSION: VCI can be used to optimize postharvest
      treatments to minimize meat shrinkage. This method can also be applied to other
      shellfish such as oysters and clams.

PMID- 24022836
TI  - Post-hatching development of in vitro bovine embryos from day 7 to 14 in vivo
      versus in vitro.
AB  - This study evaluates the post-hatching development of in vitro-produced (IVP)
      embryos until Day 14. On Day 7, IVP embryos were either transferred to recipient
      uteruses or placed in a post-hatching development (PHD) system. As a control
      group, in vivo-produced (IVV), Day-7 embryos were also transferred to recipient
      uteruses. All groups were collected on Day 14 and were morphologically evaluated.
      Day-7 and Day-14 IVV and IVP embryos were used for quantification of eight genes
      (PLAC8, CD9, SLC2A1, SLC2A3, KRT8, SOD2, HSP1A1, and IFNT2) by reverse
      transcriptase qPCR. Day-14 embryos from the PHD system were smaller (2.92 +/-
      0.45 mm) and had a lower embryonic disk diameter (0.14 +/- 0.00 mm) than those
      produced by IVV (24.18 +/- 3.71; 0.29 +/- 0.03 mm, respectively) or IVP (19.06 +/
      2.43; 0.28 +/- 0.01 mm) culture and transferred to the uterus (P > 0.05). Day-7
      IVP embryos had a higher expression of the HSP1A1, SCL2A1, and SCL2A3 genes than
      IVV embryos. When these embryos were cultured in the uterus, no differences in
      gene expression were observed on Day 14. Conversely, Day-14 IVP embryos cultured
      in the PHD system showed a higher expression of PLAC8, SOD2, and SLC2A3 genes. It
      is concluded that Day-7 IVP embryos are different from IVV embryos in regards to
      gene expression, although exposure to the uterine environment during the
      elongation period allowed the IVP embryos to overcome this difference. In
      contrast, IVP embryos cultured in the PHD system were morphologically and
      molecularly different, being of poorer quality than those cultured in the uterus.

PMID- 24022837
TI  - Letter to the editor concerning the editorial ''Innovation in orthopaedic surgery
      as it relates to evidence-based practice'' by M. Hofbauer, B. Muller, C. D.
      Murawski, J. Karlsson and Freddie H. Fu.

PMID- 24022838
TI  - Unprecedented activation and CO2 capture properties of an elastic single-molecule
      trap.
AB  - The activation and CO2 capture properties of a microporous metal-organic
      framework with elastic single-molecule traps were systematically investigated.
      This material shows a unique low-energy gas-purge activation capability, high CO2
      adsorption selectivities over various gases and optimized working capacities per
      energy of 2.9 mmol kJ(-1) at 128  degrees C. 

PMID- 24022839
TI  - Native and rearranged ALK copy number and rearranged cell count in non-small cell
      lung cancer: implications for ALK inhibitor therapy.
AB  - BACKGROUND: Patients with anaplastic lymphoma kinase (ALK)-positive non-small
      cell lung cancer (NSCLC) respond to ALK inhibitors. Clinically, the presence of
      >=15% cells with rearrangements identified on break-apart fluorescence in situ
      hybridization (FISH) classifies tumors as positive. Increases in native and
      rearranged ALK copy number also occur. METHODS: In total, 1426 NSCLC clinical
      specimens (174 ALK-positive specimens and 1252 ALK-negative specimens) and 24 ALK
      negative NSCLC cell lines were investigated. ALK copy number and genomic status
      were assessed by FISH. RESULTS: Clinical specimens with 0% to 9%, 10% to 15%, 16%
      to 30%, 31% to 50%, and >50% ALK-positive cells were identified in 79.3%, 8.5%,
      1.4%, 2.7%, and 8.1%, respectively. An increased native ALK copy number (>=3
      copies per cell in >=40% of cells) was detected in 19% of ALK-positive tumors and
      in 62% of ALK-negative tumors. In ALK-negative tumors, abundant, focal
      amplification of native ALK was rare (0.8%). Other atypical patterns occurred in
      approximately 6% of tumors. The mean native ALK copy number ranged from 2.1 to
      6.9 copies in cell lines and was not correlated with crizotinib sensitivity (50%
      inhibitory concentration, 0.34-2.8 MUM; r = 0.279; P = .1764). Neither native or
      rearranged ALK copy number nor the percentage of positive cells correlated with
      extra-central nervous system progression-free survival in ALK-positive patients
      who were receiving crizotinib. CONCLUSIONS: Overall, 8.5% of tumors fell below
      the established positivity threshold by <=5%. Further investigation of ALK by
      other diagnostic techniques in such cases may be warranted. Native ALK copy
      number increases alone were not associated with sensitivity to ALK inhibition in
      vitro. However, rare, complex patterns of increased native ALK in patients should
      be studied further; because, otherwise, atypical rearrangements contained within
      these may be missed.

PMID- 24022840
TI  - Transmit and receive RF fields determination from a single low-tip-angle gradient
      echo scan by scaling of SVD data.
AB  - PURPOSE: A new method, called Transmit and Receive Patterns from Low-Tip-angle
      gradient-Echo Images (TRIPLET), is described which simultaneously maps the B1+
      and B1- fields of a transmit/receive radiofrequency coil array. The input data
      are low-tip-angle gradient-echo images, which can be acquired in a relatively
      short scanning time. THEORY AND METHODS: For each voxel in the field of view, a
      matrix can be assembled with the low-tip-angle gradient-echo image values of the
      radiofrequency coil array. Applying the singular value decomposition to those
      matrices, datasets are obtained which show a high resemblance with the true B1+
      and B1- fields. These datasets are a voxel-wise scaled version of the true
      radiofrequency maps. The channel independent scaling parameters can be found by
      implicitly forcing the reconstructed fields to be solutions of the Maxwell
      equations. This is achieved by introducing a multipole expansion consisting of
      Bessel/Fourier functions. RESULTS: Two FDTD simulated radiofrequency fields for
      two coil array combinations at 7 T and a measured, in vivo dataset at 7 T are
      investigated to illustrate the singular value decomposition analysis of the low
      tip-angle gradient-echo images and to show how the B1+ and B1- fields can be
      reconstructed by Transmit and Receive Patterns from Low-Tip-angle gradient-Echo
      Images. CONCLUSION: The Transmit and Receive Patterns from Low-Tip-angle gradient
      Echo Images algorithm can convert the datasets from singular value decomposition
      analysis of low-tip-angle gradient-echo images to true B1+ and B1- fields.

PMID- 24022841
TI  - CXCL12 induces lung cancer cell migration by polarized mtDNA redistribution.
AB  - Instability of mitochondrial DNA (mtDNA) has been associated with the initiation
      and development of cancer, but the specific role of mtDNA in the invasiveness and
      migration of cancer cells remains unclear. In this study, we investigated whether
      the chemokine CXCL12 causes intact mitochondria to redistribute in cancer cells
      and, in this way, to increase cell invasiveness and migration. A549 lung cancer
      cells with intact mtDNA (mtDNA+) and rho(0)A549 cells depleted of mtDNA (mtDNA-)
      by long-term ethidium bromide incubation were examined for their responses to
      CXCL12 in a transwell migration assay and for mitochondrial distribution by
      fluorescence microscopy. Intact A549 cells showed significantly increased
      migration and increased polar distribution of mitochondria (asymmetry)in response
      to CXCL12. However, rho(0)A549 cells showed no changes in mitochondrial
      distribution in response to CXCL12, and only a few rho(0)A549 cells migrated
      across the transwell membrane after CXCL12 treatment. These results demonstrate
      that, in A549 lung cancer cells, intact mitochondrial DNA is necessary for
      mitochondrial redistribution and a chemotactic response to CXCL12.

PMID- 24022842
TI  - Humane scientific writing: comment on the article by Pisetsky.

PMID- 24022843
TI  - Prostate volume correlates with diabetes in elderly benign prostatic hyperplasia
      patients.
AB  - BACKGROUND: To evaluate the relationship between prostate volume (PV) and
      diabetes mellitus (DM) in geriatric benign prostatic hyperplasia (BPH) patients.
      METHODS: One hundred and seventeen geriatric patients with BPH were
      retrospectively studied between 2008 and 2009. Patients were divided into two
      groups: BPH and BPH with DM group. The effects of indexes of DM, including
      fasting blood glucose (FBG), 2-h postprandial blood glucose, glycosylated
      hemoglobin (HbA1c), fasting insulin (FINS), insulin resistance (IR) index,
      prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS), and
      lower urinary tract symptoms (LUTS) were evaluated. RESULTS: The values of PV (P
      = 0.005), PSA (P = 0.013), and IPSS (P = 0.01) in the BPH patients with DM group
      were significantly higher than in the BPH group. The values of PV (P = 0.002) and
      PSA (P = 0.006) in the BPH patients with elevated FBG were significantly higher
      than in the BPH patients with normal FBG. BPH patients with elevated HbA1c had
      significantly higher PV than BPH patients with normal HbA1c (P = 0.046). BPH with
      hyperinsulinemia group showed significantly higher PV (P = 0.017) and longer
      duration of LUTS (P = 0.031) than BPH patients with normal FINS. Similarly, BPH
      patients with IR had higher PV (P = 0.004) and longer duration of LUTS (P =
      0.036) than BPH patients without IR. The logistic regression analysis showed that
      FBG and FINS were the risk factors for BPH. CONCLUSIONS: Our study demonstrates
      that PV is closely correlated with diabetes and diabetes has a direct effect on
      the occurrence and development of BPH.

PMID- 24022844
TI  - Surgically treated bladder hemangiopericytoma/solitary fibrous tumor: report of a
      12-year asymptomatic follow-up.
AB  - Hemangiopericytoma (HPC)/solitary fibrous tumor (SFT) is an uncommon vascular
      tumor suggested to be originating from pericytes. There are few reports on
      bladder HPC/SFT. We present a case of huge bladder HPC/SFT measuring 13.9 * 12.2
      * 11.1 cm with invasion to right iliac vein in a 54-year-old man. The patient
      underwent radical surgical tumor excision without chemotherapy or radiotherapy.
      The patient is symptom-free without recurrence or metastasis during the 12-year
      follow-up period. This case is the longest follow-up reported to date for bladder
      HPC/SFT.

PMID- 24022845
TI  - Apparent diffusion coefficient value as a biomarker reflecting morphological and
      biological features of prostate cancer.
AB  - PURPOSE: To assess whether there is an association between the apparent diffusion
      coefficient (ADC) value and the pathological characteristics of prostate cancer.
      METHODS: The study cohort consisted of 29 consecutive patients with prostate
      cancer treated with radical prostatectomy. All patients underwent diffusion
      weighted MRI before the prostate biopsy. In 42 tumor foci, the associations of
      the ADC values with the clinicopathological characteristics and Ki-67 labeling
      index (LI) were analyzed. RESULTS: High-grade cancers (Gleason score [GS] >= 4 +
      3), larger cancers (maximum diameter (MD) >= 16 mm), and highly proliferating
      cancers (Ki-67 LI >= 4.43 %) had significantly lower ADC values, respectively (P
      < .001, P = .008, and P = .044, respectively). There was no significant
      difference in ADC value according to age, prostate-specific antigen, presence of
      extra-prostatic extension, and intra-tumoral stroma proportion. Multivariate
      analysis showed that GS, Ki-67 LI, and MD had independent and significant
      correlations with ADC value (P < .001, P = .006, and P = .002, respectively). Low
      ADC tumors (<0.52 * 10(-3) mm(2)/s) are likely to be high-grade cancer foci
      compared with high ADC tumors (relative risk: 65.2). The sensitivity and
      specificity of the ADC value to predict high-grade cancer foci are 81.8 and 93.5
      %, respectively. CONCLUSIONS: A low ADC value reflects the morphological and
      biological features of prostate cancer. Analyzing the ADC value may make it
      possible to more precisely predict the cancer aggressiveness of each focus before
      treatment.

PMID- 24022846
TI  - Basic techniques for long distance axon tracing in the spinal cord.
AB  - The regeneration of axons after a spinal cord injury or disease is attracting a
      significant amount of interest among researchers. Being able to assess these
      axons in terms of morphology, length and origin is essential to our understanding
      of the regeneration process. Recently, two specific axon tracers have gained much
      recognition; biotinylated dextran amine (BDA) 10 kDa as an anterograde tracer and
      cholera toxin-B as a retrograde tracer. However, there are still several
      complexities when using these tracers, including the volume that should be
      administered and the best administration site so that a significant amount of
      axons are labeled in the area of interest. In this article, we describe some
      simple procedures for injecting the tracers and detecting them. We also
      quantified the number of axons at different locations of the spinal cord. Our
      results show axons labeled from motor cortex injections traveled down to the
      lumbosacral spinal cord in 2 weeks, while BDA injections into the lateral
      vestibular nucleus and reticular formation took 3 weeks to label axons in the
      lumbosacral spinal cord. Moreover, this protocol outlines some basic procedures
      that could be used in any laboratory and gives insight into the number of axons
      labeled and how procedures could be tailored to meet specific researcher's needs.

PMID- 24022847
TI  - Plasmid deficiency in urogenital isolates of Chlamydia trachomatis reduces
      infectivity and virulence in a mouse model.
AB  - We hypothesized that the plasmid of urogenital isolates of Chlamydia trachomatis
      would modulate infectivity and virulence in a mouse model. To test this
      hypothesis, we infected female mice in the respiratory or urogenital tract with
      graded doses of a human urogenital isolate of C. trachomatis, serovar F,
      possessing the cognate plasmid. For comparison, we inoculated mice with a plasmid
      free serovar F isolate. Following urogenital inoculation, the plasmid-free
      isolate displayed significantly reduced infectivity compared with the wild-type
      strain with the latter yielding a 17-fold lower infectious dose to yield 50%
      infection. When inoculated via the respiratory tract, the plasmid-free isolate
      exhibited reduced infectivity and virulence (as measured by weight change) when
      compared to the wild-type isolate. Further, differences in infectivity, but not
      in virulence were observed in a C. trachomatis, serovar E isolate with a deletion
      within the plasmid coding sequence 1 when compared to a serovar E isolate with no
      mutations in the plasmid. We conclude that plasmid loss reduces virulence and
      infectivity in this mouse model. These findings further support a role for the
      chlamydial plasmid in infectivity and virulence in vivo.

PMID- 24022848
TI  - ICSH/ICCS practice guidelines special issue.

PMID- 24022849
TI  - Validation of cell-based fluorescence assays: practice guidelines from the
      International Council for Standardization of Haematology and International
      Clinical Cytometry Society.

PMID- 24022850
TI  - Validation of cell-based fluorescence assays: practice guidelines from the ICSH
      and ICCS - part I - rationale and aims.
AB  - Flow cytometry and other technologies of cell-based fluorescence assays are as a
      matter of good laboratory practice required to validate all assays, which when in
      clinical practice may pass through regulatory review processes using criteria
      often defined with a soluble analyte in plasma or serum samples in mind. Recently
      the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in
      the U.S. regarding their regulatory interest in laboratory developed tests (LDTs)
      or so-called "home brew" assays performed in clinical laboratories. The absence
      of well-defined guidelines for validation of cell-based assays using fluorescence
      detection has thus become a subject of concern for the International Council for
      Standardization of Haematology (ICSH) and International Clinical Cytometry
      Society (ICCS). Accordingly, a group of over 40 international experts in the
      areas of test development, test validation, and clinical practice of a variety of
      assay types using flow cytometry and/or morphologic image analysis were invited
      to develop a set of practical guidelines useful to in vitro diagnostic (IVD)
      innovators, clinical laboratories, regulatory scientists, and laboratory
      inspectors. The focus of the group was restricted to fluorescence reporter
      reagents, although some common principles are shared by immunohistochemistry or
      immunocytochemistry techniques and noted where appropriate. The work product of
      this two year effort is the content of this special issue of this journal, which
      is published as 5 separate articles, this being Validation of Cell-based
      Fluorescence Assays: Practice Guidelines from the ICSH and ICCS - Part I -
      Rationale and aims. (c) 2013 International Clinical Cytometry Society. 

PMID- 24022851
TI  - Validation of cell-based fluorescence assays: practice guidelines from the ICSH
      and ICCS - part II - preanalytical issues.
AB  - Flow cytometry and other technologies of cell-based fluorescence assays are as a
      matter of good laboratory practice required to validate all assays, which when in
      clinical practice may pass through regulatory review processes using criteria
      often defined with a soluble analyte in plasma or serum samples in mind. Recently
      the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in
      the U.S. regarding their regulatory interest in laboratory developed tests (LDTs)
      or so-called "home brew" assays performed in clinical laboratories. The absence
      of well-defined guidelines for validation of cell-based assays using fluorescence
      detection has thus become a subject of concern for the International Council for
      Standardization of Haematology (ICSH) and International Clinical Cytometry
      Society (ICCS). Accordingly, a group of over 40 international experts in the
      areas of test development, test validation, and clinical practice of a variety of
      assay types using flow cytometry and/or morphologic image analysis were invited
      to develop a set of practical guidelines useful to in vitro diagnostic (IVD)
      innovators, clinical laboratories, regulatory scientists, and laboratory
      inspectors. The focus of the group was restricted to fluorescence reporter
      reagents, although some common principles are shared by immunohistochemistry or
      immunocytochemistry techniques and noted where appropriate. The work product of
      this two year effort is the content of this special issue of this journal, which
      is published as 5 separate articles, this being Validation of Cell-based
      Fluorescence Assays: Practice Guidelines from the ICSH and ICCS - Part II -
      Preanalytical issues. (c) 2013 International Clinical Cytometry Society. 

PMID- 24022852
TI  - Validation of cell-based fluorescence assays: practice guidelines from the ICSH
      and ICCS - part III - analytical issues.
AB  - Clinical diagnostic assays, may be classified as quantitative, quasi-quantitative
      or qualitative. The assay's description should state what the assay needs to
      accomplish (intended use or purpose) and what it is not intended to achieve. The
      type(s) of samples (whole blood, peripheral blood mononuclear cells (PBMC), bone
      marrow, bone marrow mononuclear cells (BMMC), tissue, fine needle aspirate,
      fluid, etc.), instrument platform for use and anticoagulant restrictions should
      be fully validated for stability requirements and specified. When applicable,
      assay sensitivity and specificity should be fully validated and reported; these
      performance criteria will dictate the number and complexity of specimen samples
      required for validation. Assay processing and staining conditions
      (lyse/wash/fix/perm, stain pre or post, time and temperature, sample stability,
      etc.) should be described in detail and fully validated.

PMID- 24022853
TI  - Validation of cell-based fluorescence assays: practice guidelines from the ICSH
      and ICCS - part IV - postanalytic considerations.
AB  - Flow cytometry and other technologies of cell-based fluorescence assays are as a
      matter of good laboratory practice required to validate all assays, which when in
      clinical practice may pass through regulatory review processes using criteria
      often defined with a soluble analyte in plasma or serum samples in mind. Recently
      the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in
      the U.S. regarding their regulatory interest in laboratory developed tests (LDTs)
      or so-called home brew assays performed in clinical laboratories. The absence of
      well-defined guidelines for validation of cell-based assays using fluorescence
      detection has thus become a subject of concern for the International Council for
      Standardization of Haematology (ICSH) and International Clinical Cytometry
      Society (ICCS). Accordingly, a group of over 40 international experts in the
      areas of test development, test validation, and clinical practice of a variety of
      assay types using flow cytometry and/or morphologic image analysis were invited
      to develop a set of practical guidelines useful to in vitro diagnostic (IVD)
      innovators, clinical laboratories, regulatory scientists, and laboratory
      inspectors. The focus of the group was restricted to fluorescence reporter
      reagents, although some common principles are shared by immunohistochemistry or
      immunocytochemistry techniques and noted where appropriate. The work product of
      this two year effort is the content of this special issue of this journal, which
      is published as 5 separate articles, this being Validation of Cell-based
      Fluorescence Assays: Practice Guidelines from the ICSH and ICCS - Part IV -
      Postanalytic considerations.

PMID- 24022854
TI  - Validation of cell-based fluorescence assays: practice guidelines from the ICSH
      and ICCS - part V - assay performance criteria.
AB  - Multi-color flow cytometry is a unique technology, which enables the analysis of
      heterogeneous cellular systems and provides multiparametric information on a cell
      by-cell basis. A variety of factors contribute to the complexity of validating
      cell-based flow cytometric methods, including the lack of fully characterized
      cellular reference materials and the difficulty in obtaining, or creating,
      samples with varying levels of a given cell type or varying levels of expression
      of a given antigen. This document summarizes validation requirements and
      describes validation strategies for quasi-quantitative and qualitative cell-based
      flow cytometric assays.

PMID- 24022855
TI  - Concerning the article by de Carvalho Bittencourt et al.: Value of HIV patients
      with regular follow-up as in-house internal controls of flow cytometry
      measurement of lymphocyte subsets.

PMID- 24022856
TI  - Determination of optimal replicate number for validation of imprecision using
      fluorescence cell-based assays: proposed practical method.
AB  - BACKGROUND: Assay validation includes determination of inherent imprecision
      across the reportable range. However, specific practical guidelines for
      determinations of precision for cell-based fluorescence assays performed on flow
      cytometers are currently lacking. METHODS: Replicates of 10 or 20 measurements
      were obtained for flow cytometric assays developed for clinical in vitro
      diagnostic use, including neutrophil CD64 expression for infection/sepsis
      detection, fetal red cell enumeration for fetomaternal hemorrhage detection,
      human equilibrative nucleoside transporter 1 quantitation in leukocytes for
      possible correlation with drug responsiveness, and CD34+ hematopoietic stem cell
      enumeration of apheresis products, using up to three different instrument
      platforms for each assay. For each assay, the mean, 95% confidence intervals (95%
      CIs) of the mean, standard deviation, and coefficient of variation (CV) of
      sequential replicates were determined. RESULTS: For all assays and most
      instrument platforms, <5 replicates were found adequate to validate assay
      imprecision levels below the 5-10% CV for repeatability claimed by the
      manufacturers of these assays. Results plotted as a novel parameter derived from
      the 95% CI and the cumulative mean for replicates, termed variance factor (VF),
      provide a data-driven means for determining optimal replicate numbers.
      CONCLUSIONS: The novel VF can provide information to guide the practical
      selection of optimal replicate numbers for validation of imprecision in flow
      cytometric assays. The optimal number of replicates was assay and instrument
      platform dependent. Our findings indicate that three to four replicates are
      sufficient for most flow cytometric assays and instrument combinations, rather
      than the higher numbers suggested by CLSI guidelines for soluble analytes.

PMID- 24022857
TI  - Saliva sampling method affects performance of a salivary alpha-amylase biosensor.
AB  - OBJECTIVES: Prompted by the discordance between a standardized salivary alpha
      amylase (sAA) biosensor applied in clinical settings and a reference laboratory
      analyzer, we examined the impact of the saliva sampling method on the analytic
      performance of the biosensor. METHODS: Direct mouth readings using the biosensor
      from 31 normal, healthy volunteers were compared to biosensor and conventional
      assay readings obtained from saliva samples collected concurrently by passive
      drool and processed in three different ways (unprocessed, thawed, and thawed and
      centrifuged). RESULTS: The direct readings from the mouth showed consistently
      lower sAA values (Ps < 0.01) compared to all other combinations of sample
      processing and quantification platforms (biosensor vs. conventional assay).
      Readings obtained from passive drool saliva were strongly correlated with one
      another, and Bland-Altman plots of agreement indicated a smaller discrepancy
      between conventional and biosensor readings obtained with passive drool when
      compared to the direct mouth readings. CONCLUSIONS: Our study indicates that the
      analytical performance of the sAA biosensor is influenced significantly by the
      saliva sampling method. In contrast to the relatively imprecise direct mouth
      measurements, biosensor sAA levels established indirectly from passive drool
      saliva samples provide more accurate estimation of sAA levels, even after
      intermediary processing steps (e.g., freezing, thawing, centrifugation).

PMID- 24022858
TI  - Effect of the moisture content of forced hot air on the postharvest quality and
      bioactive compounds of mango fruit (Mangifera indica L. cv. Manila).
AB  - BACKGROUND: The effectiveness of hot air treatments in controlling decay and
      insects in mango fruit has been demonstrated and has usually been assessed as a
      function of the temperature of the heated air and the duration of the treatment.
      However, the contribution of the moisture content of the heated air has received
      little attention, especially with regard to fruit quality. In this study, mango
      fruits (cv. Manila) at mature-green stage were treated with moist (95% relative
      humidity (RH)) or dry (50% RH) hot forced air (43  degrees C, at 2.5 m s(-1) for
      220 min) and then held at 20  degrees C for 9 days and evaluated periodically.
      RESULTS: The heating rate was higher with moist air. Treatments with moist and
      dry air did not cause injury to the fruit. Treatment with moist air temporarily
      slowed down color development, softening, weight loss and beta-carotene
      biosynthesis. This slowing down was clearly observed during the first 4-5 days at
      20  degrees C. However, non-heated fruit and fruit heated with dry air showed
      similar quality at the end of storage. CONCLUSION: The moisture content of the
      heating air differentially modulated the postharvest ripening of 'Manila'
      mangoes. Moist air temporarily slowed down the ripening process of this mango
      cultivar.

PMID- 24022860
TI  - The rectovaginal septum: visible on magnetic resonance images of women with Mayer
      Rokitansky-Kuster-Hauser syndrome (Mullerian agenesis).
AB  - INTRODUCTION AND HYPOTHESIS: Ongoing debate exists about whether the rectovaginal
      septum (Denonvilliers' fascia) is myth or reality. This study evaluates magnetic
      resonance images (MRI) of women with Mullerian agenesis for the presence of
      fascial layers between the rectum and the bladder to test the hypothesis that
      this layer exists in the absence of the vagina. METHODS: This is a secondary
      analysis of a study describing MRI aspects in women with vaginal agenesis before
      and after laparoscopic Vecchietti procedure. Study participants (n =16) had a
      multiplanar pelvic MR scan. Images were evaluated independently by two
      investigators (MH, JOLD) for the appearance of layers separate from the bladder
      and rectum in the area of interest, with characteristic anatomical features of
      the septum. RESULTS: Participants' mean age was 19.4+/-2.6 years +/- standard
      deviation (SD). In 12 of 16 patients (75 %) a distinct layer between rectum and
      bladder was identified in either the axial(4/16; 25 %) or sagittal (12/16; 75 %)
      scan or both. Characteristic anatomical features included lateral attachment to
      the levator ani muscle, cranial fusion to the cul-de-sac peritoneum,and caudal
      insertion into the perineal body.Conclusions Three quarters of women with
      Mullerian agenesis have a visible layer between bladder and rectum. As none of
      the participants had a vagina, these results support the existence of a
      rectovaginal septum, separate from a vaginal adventitia.

PMID- 24022861
TI  - A NEIL1 single nucleotide polymorphism (rs4462560) predicts the risk of radiation
      induced toxicities in esophageal cancer patients treated with definitive
      radiotherapy.
AB  - BACKGROUND: To assess the association between single nucleotide polymorphisms
      (SNPs) of base-excision repair genes and clinical outcomes, the roles of genetic
      variants of 3 selected genes-flap structure-specific endonuclease 1 (FEN1), 8
      hydroxyguanine DNA glycosylase (hOGG1), and nei endonuclease VIII-like 1 (NEIL1)-
      were investigated in radiation-induced esophageal toxicity (RIET), radiation
      pneumonitis (RP), and overall survival (OS) after radio(chemo)therapy in patients
      with esophageal squamous cell carcinoma (ESCC). METHODS: NEIL1 reference SNP
      4462560 (rs4462560) and rs7402844, hOGG1 rs1052133 and rs293795, and FEN1
      rs4246215 and rs174538 were genotyped in 187 patients with ESCC who received
      definitive radiotherapy with or without chemotherapy. Kaplan-Meier cumulative
      probabilities and Cox proportional hazards regression models were used to assess
      the effect of the genotypes on the risk of RIET, RP, and OS. RESULTS: The authors
      observed that patients who had the NEIL1 rs4462560 GC/CC genotype had a
      statistically significantly lower risk of both grade >= 2 acute radiation-induced
      esophageal toxicity (RIET) (adjusted hazard ratio [HR], 0.421; 95% confidence
      interval [CI], 0.207-0.856; P = .017) and grade >= 2 acute radiation pneumonitis
      (RP) (adjusted HR, 0.392; 95% CI, 0.163-0.946; P = .037) compared with patients
      who had the GG genotype, but the genotype did not affect OS (adjusted HR, 0.778;
      95% CI, 0.471-1.284; P = .326). There were no significant findings for other the
      SNPs under investigation. CONCLUSIONS: The NEIL1 rs4462560 SNP may serve as a
      predictor of acute RIET and RP risk but not of OS. Larger prospective studies are
      needed to validate these findings.

PMID- 24022863
TI  - Relationship between the diffusion time and the diffusion MRI signal observed at
      17.2 Tesla in the healthy rat brain cortex.
AB  - PURPOSE: To investigate the diffusion time dependency of water diffusion in
      cortical brain tissue. METHODS: We have combined an oscillating gradient spin
      echo (OGSE) and a pulse gradient spin echo (PGSE) spin-echo sequence to acquire
      diffusion-weighted MRI images in vivo in healthy rat brains over a wide range of
      diffusion times (1.9-29.2 ms) and estimated the parameters of the biexponential
      and cumulant expansion diffusion MRI signal models. Diffusion images were
      obtained at 17.2 Tesla with maximum gradient strength of 1000 mT/m allowing 40 b
      values up to approximately 4000 s/mm(2). RESULTS: At all diffusion times the log
      plot of diffusion signal attenuation versus b value was curved, confirming that
      diffusion is not free, even at very short diffusion times. This suggests that the
      length scale of obstacles to diffusion must be smaller than the corresponding
      shortest observed diffusion distance (approximately 1.7 MUm). The diffusion MRI
      signal was also not found in a steady-state, even at our longest diffusion time
      (29.2 ms), suggesting some degree of segregation of water in pools. CONCLUSION:
      Overall, the results showed that the parameters derived from the two diffusion
      models could not well be related to specific tissue features. More specific
      models must be developed taking into account diffusion signal behavior at high b
      values and short diffusion times.

PMID- 24022862
TI  - Suboptimal inhibition of platelet cyclooxygenase 1 by aspirin in systemic lupus
      erythematosus: association with metabolic syndrome.
AB  - OBJECTIVE: Low-dose aspirin prevents platelet aggregation by suppressing
      thromboxane A2 (TXA2 ) synthesis. However, in some individuals TXA2 suppression
      by aspirin is impaired, indicating suboptimal inhibition of platelet
      cyclooxygenase 1 (COX-1) by aspirin. Because patients with systemic lupus
      erythematosus (SLE) have increased risk of thrombotic events, many receive
      aspirin; however, the efficacy of aspirin in SLE has not been determined. We
      examined the hypothesis that aspirin response is impaired in SLE. METHODS: We
      assessed the effect of aspirin by measuring concentrations of the stable
      metabolite of TXA2 , serum thromboxane B2 (sTXB2 ), before and after treatment
      with daily aspirin (81 mg) for 7 days in 34 patients with SLE and 36 control
      subjects. The inability to suppress sTXB2 synthesis to <10 ng/ml represents
      suboptimal inhibition of platelet COX-1 by aspirin. RESULTS: Aspirin almost
      completely suppressed sTXB2 in control subjects to median 1.5 ng/ml
      (interquartile range [IQR] 0.8-2.7) but had less effect in patients with SLE
      (median 3.1 ng/ml [IQR 2.2-5.3]) (P = 0.002). A suboptimal effect of aspirin was
      present in 15% (5 of 34) of the patients with SLE but not in control subjects (0
      of 36) (P = 0.023). Incomplete responders were more likely to have metabolic
      syndrome (P = 0.048), obesity (P = 0.048), and higher concentrations of C
      reactive protein (CRP) (P = 0.018). CONCLUSION: The pharmacologic effect of
      aspirin is suboptimal in 15% of patients with SLE but in none of the control
      subjects, and the suboptimal response was associated with metabolic syndrome,
      obesity, and higher CRP concentrations.

PMID- 24022864
TI  - 6-Mercaptopurine augments glucose transport activity in skeletal muscle cells in
      part via a mechanism dependent upon orphan nuclear receptor NR4A3.
AB  - The purine anti-metabolite 6-mercaptopurine (6-MP) is widely used for the
      treatment of leukemia and inflammatory diseases. The cellular effects of 6-MP on
      metabolism remain unknown; however, 6-MP was recently found to activate the
      orphan nuclear receptor NR4A3 in skeletal muscle cell lines. We have reported
      previously that NR4A3 (also known as NOR-1, MINOR) is a positive regulator of
      insulin sensitivity in adipocytes. To further explore the role of NR4A3
      activation in insulin action, we explored whether 6-MP activation of NR4A3 could
      modulate glucose transport system activity in L6 skeletal muscle cells. We found
      that 6-MP increased both NR4A3 expression and NR4A3 transcriptional activity and
      enhanced glucose transport activity via increasing GLUT4 translocation in both
      basal and insulin-stimulated L6 cells in an NR4A3-dependent manner. Furthermore,
      6-MP increased levels of phospho-AS160, although this effect was not modulated by
      NR4A3 overexpression or knockdown. These primary findings provide a novel proof
      of principle that 6-MP, a small molecule NR4A3 agonist, can augment glucose
      uptake in insulin target cells, although this occurs via both NR4A3-dependent and
      -independent actions; the latter is related to an increase in phospho-AS160.
      These results establish a novel target for development of new treatments for
      insulin resistance.

PMID- 24022865
TI  - Altered content of AMP-activated protein kinase isoforms in skeletal muscle from
      spinal cord injured subjects.
AB  - AMP-activated protein kinase (AMPK) is a pivotal regulator of energy homeostasis.
      Although downstream targets of AMPK are widely characterized, the physiological
      factors governing isoform expression of this protein kinase are largely unknown.
      Nerve/contractile activity has a major impact on the metabolic phenotype of
      skeletal muscle, therefore likely to influence AMPK isoform expression. Spinal
      cord injury represents an extreme form of physical inactivity, with concomitant
      changes in skeletal muscle metabolism. We assessed the influence of longstanding
      and recent spinal cord injury on protein abundance of AMPK isoforms in human
      skeletal muscle. We also determined muscle fiber type as a marker of glycolytic
      or oxidative metabolism. In subjects with longstanding complete injury, protein
      abundance of the AMPKgamma3 subunit, as well as myosin heavy chain (MHC) IIa and
      IIx, were increased, whereas abundance of the AMPKgamma1 subunit and MHC I were
      decreased. Similarly, abundance of AMPKgamma3 and MHC IIa proteins were
      increased, whereas AMPKalpha2, -beta1, and -gamma1 subunits and MHC I abundance
      was decreased during the first year following injury, reflecting a more
      glycolytic phenotype of the skeletal muscle. However, in incomplete cervical
      lesions, partial recovery of muscle function attenuated the changes in the
      isoform profile of AMPK and MHC. Furthermore, exercise training (electrically
      stimulated leg cycling) partly normalized mRNA expression of AMPK isoforms. Thus,
      physical activity affects the relative expression of AMPK isoforms. In
      conclusion, skeletal muscle abundance of AMPK isoforms is related to physical
      activity and/or muscle fiber type. Thus, physical/neuromuscular activity is an
      important determinant of isoform abundance of AMPK and MCH. This further
      underscores the need for physical activity as part of a treatment regimen after
      spinal cord injury to maintain skeletal muscle metabolism.

PMID- 24022866
TI  - In vivo magnetic resonance of hyperpolarized [(13)C1]pyruvate: metabolic dynamics
      in stimulated muscle.
AB  - The metabolic status of muscle changes according to the energetic demands of the
      organism. Two key regulators of these changes include exercise and insulin, with
      exercise eliciting catabolic expenditure within seconds and insulin enabling
      anabolic energy investment over minutes to hours. This study explores the
      potential of time-resolved hyperpolarized dynamic (13)C spectroscopy to
      characterize the in vivo metabolic phenotype of muscle during functional and
      biochemical insulin-induced stimulation of muscle. Using [(13)C1]pyruvic acid as
      a tracer, we find that despite the different time scales of these forms of
      stimulation, increases in pyruvate label transport and consumption and
      concomitant increases in initial rates of the tracer metabolism to lactate were
      observed for both stimuli. By contrast, rates of tracer metabolism to labeled
      alanine increased incrementally for insulin but remained unchanged following
      exercise-like muscle stimulation. Kinetic analysis revealed that branching of the
      hyperpolarized [(13)C]pyruvate tracer between lactate and alanine provides
      significant tissue-specific biomarkers that distinguish between anabolic and
      catabolic fates in vivo according to the routing of metabolites between
      glycolytic and amino acid pathways.

PMID- 24022867
TI  - Palmitoleic acid (n-7) increases white adipocyte lipolysis and lipase content in
      a PPARalpha-dependent manner.
AB  - We investigated whether palmitoleic acid, a fatty acid that enhances whole body
      glucose disposal and suppresses hepatic steatosis, modulates triacylglycerol
      (TAG) metabolism in adipocytes. For this, both differentiated 3T3-L1 cells
      treated with either palmitoleic acid (16:1n7, 200 MUM) or palmitic acid (16:0,
      200 MUM) for 24 h and primary adipocytes from wild-type or PPARalpha-deficient
      mice treated with 16:1n7 (300 mg.kg(-1).day(-1)) or oleic acid (18:1n9, 300
      mg.kg(-1).day(-1)) by gavage for 10 days were evaluated for lipolysis, TAG, and
      glycerol 3-phosphate synthesis and gene and protein expression profile. Treatment
      of differentiated 3T3-L1 cells with 16:1n7, but not 16:0, increased basal and
      isoproterenol-stimulated lipolysis, mRNA levels of adipose triglyceride lipase
      (ATGL) and hormone-sensitive lipase (HSL) and protein content of ATGL and
      pSer(660)-HSL. Such increase in lipolysis induced by 16:1n7, which can be
      prevented by pharmacological inhibition of PPARalpha, was associated with higher
      rates of PPARalpha binding to DNA. In contrast to lipolysis, both 16:1n7 and 16:0
      increased fatty acid incorporation into TAG and glycerol 3-phosphate synthesis
      from glucose without affecting glyceroneogenesis and glycerokinase expression.
      Corroborating in vitro findings, treatment of wild-type but not PPARalpha
      deficient mice with 16:1n7 increased primary adipocyte basal and stimulated
      lipolysis and ATGL and HSL mRNA levels. In contrast to lipolysis, however, 16:1n7
      treatment increased fatty acid incorporation into TAG and glycerol 3-phosphate
      synthesis from glucose in both wild-type and PPARalpha-deficient mice. In
      conclusion, palmitoleic acid increases adipocyte lipolysis and lipases by a
      mechanism that requires a functional PPARalpha.

PMID- 24022868
TI  - Dehydroepiandrosterone exerts antiglucocorticoid action on human preadipocyte
      proliferation, differentiation, and glucose uptake.
AB  - Glucocorticoids increase adipocyte proliferation and differentiation, a process
      underpinned by the local reactivation of inactive cortisone to active cortisol
      within adipocytes catalyzed by 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1). The adrenal sex steroid precursor dehydroepiandrosterone (DHEA) has been
      shown to inhibit 11beta-HSD1 in murine adipocytes; however, rodent adrenals do
      not produce DHEA physiologically. Here, we aimed to determine the effects and
      underlying mechanisms of the potential antiglucocorticoid action of DHEA and its
      sulfate ester DHEAS in human preadipocytes. Utilizing a human subcutaneous
      preadipocyte cell line, Chub-S7, we examined the metabolism and effects of DHEA
      in human adipocytes, including adipocyte proliferation, differentiation, 11beta
      HSD1 expression, and activity and glucose uptake. DHEA, but not DHEAS,
      significantly inhibited preadipocyte proliferation via cell cycle arrest in the
      G1 phase independent of sex steroid and glucocorticoid receptor activation.
      11beta-HSD1 oxoreductase activity in differentiated adipocytes was inhibited by
      DHEA. DHEA coincubated with cortisone significantly inhibited preadipocyte
      differentiation, which was assessed by the expression of markers of early (LPL)
      and terminal (G3PDH) adipocyte differentiation. Coincubation with cortisol,
      negating the requirement for 11beta-HSD1 oxoreductase activity, diminished the
      inhibitory effect of DHEA. Further consistent with glucocorticoid-opposing
      effects of DHEA, insulin-independent glucose uptake was significantly enhanced by
      DHEA treatment. DHEA increases basal glucose uptake and inhibits human
      preadipocyte proliferation and differentiation, thereby exerting an
      antiglucocorticoid action. DHEA inhibition of the amplification of glucocorticoid
      action mediated by 11beta-HSD1 contributes to the inhibitory effect of DHEA on
      human preadipocyte differentiation.

PMID- 24022870
TI  - Comparative effectiveness of anti-tumor necrosis factor drugs on health-related
      quality of life among patients with inflammatory arthritis.
AB  - OBJECTIVE: To compare the relative effectiveness of anti-tumor necrosis factor
      (anti-TNF) therapies on health-related quality of life (HRQOL) by inflammatory
      arthritis types. METHODS: Patients with rheumatoid arthritis (RA), ankylosing
      spondylitis (AS), and psoriatic arthritis (PsA) who had anti-TNF therapy
      (etanercept, adalimumab, or infliximab) in the Australian Rheumatology
      Association Database during 2001-2011 were assessed using the Medical Outcomes
      Study Short Form 36 (SF-36), Assessment of Quality of Life (AQoL), and Health
      Assessment Questionnaire (HAQ) disability index (DI) on a biannual basis. Linear
      regression was used for the analysis; the lack of independence in outcomes for
      multiple assessments in the same patient was taken into account using generalized
      estimating equations. RESULTS: There were 18,119 assessments (first-time drug use
      n = 12,274, subsequent use n = 3,098, and no use n = 2,747) provided by 3,033
      patients (2,240 RA, 507 AS, and 286 PsA patients) with the anti-TNF therapies.
      The effects of subsequent use versus first-time use were reduced on the SF-36
      physical component summary, AQoL, and HAQ DI scores among RA patients. After
      adjusting for therapy order, calendar year, sex, age, smoking status, and various
      medication uses, the 3 anti-TNF preparations had similar effects on the HRQOL
      measures for patients with RA, AS, or PsA. However, differences between anti-TNF
      therapies were observed in the AQoL score among PsA patients (infliximab versus
      etanercept: -0.06 [95% confidence interval (95% CI) -0.12, -0.004]) and in the SF
      36 mental component summary score among RA patients (adalimumab versus
      etanercept: -1.17 [95% CI -1.88, -0.46]). CONCLUSION: This study revealed similar
      effectiveness of etanercept, adalimumab, and infliximab on the HRQOL measures
      among Australians with RA, AS, and PsA.

PMID- 24022871
TI  - Ethnic differences in hospice enrollment following inpatient palliative care
      consultation.

PMID- 24022869
TI  - Prolactin regulates TRPV1, TRPA1, and TRPM8 in sensory neurons in a sex-dependent
      manner: Contribution of prolactin receptor to inflammatory pain.
AB  - Prolactin (PRL) is a hormone produced in the anterior pituitary but also
      synthesized extrapituitary where it can influence diverse cellular processes,
      including inflammatory responses. Females experience greater pain in certain
      inflammatory conditions, but the contribution of the PRL system to sex-dependent
      inflammatory pain is unknown. We found that PRL regulates transient receptor
      potential (TRP) channels in a sex-dependent manner in sensory neurons. At >20
      ng/ml, PRL sensitizes TRPV1 in female, but not male, neurons. This effect is
      mediated by PRL receptor (PRL-R). Likewise, TRPA1 and TRPM8 were sensitized by
      100 ng/ml PRL only in female neurons. We showed that complete Freund adjuvant
      (CFA) upregulated PRL levels in the inflamed paw of both male and female rats,
      but levels were higher in females. In contrast, CFA did not change mRNA levels of
      long and short PRL-R in the dorsal root ganglion or spinal cord. Analysis of PRL
      and PRL-R knockout (KO) mice demonstrated that basal responses to cold stimuli
      were only altered in females, and with no significant effects on heat and
      mechanical responses in both sexes. CFA-induced heat and cold hyperalgesia were
      not changed in PRL and PRL-R KO compared with wild-type (WT) males, whereas
      significant reduction of heat and cold post-CFA hyperalgesia was detected in PRL
      and PRL-R KO females. Attenuation of CFA-induced mechanical allodynia was
      observed in both PRL and PRL-R KO females and males. Thermal hyperalgesia in PRL
      KO females was restored by administration of PRL into hindpaws. Overall, we
      demonstrate a sex-dependent regulation of peripheral inflammatory hyperalgesia by
      the PRL system.

PMID- 24022872
TI  - Patient-rheumatologist communication concerning prescription medications: getting
      to the gist.
AB  - OBJECTIVE: Fuzzy trace theory was used to develop a coding scheme that captures
      the gist that patients extract from information about medication risks and
      benefits and to explore the extent to which different patients extract different
      gist representations from the same information. METHODS: Data were collected from
      2003-2007 in a study that included audiotape recording office visits that
      rheumatoid arthritis (RA) patients had with their rheumatologists. Each patient
      (n = 365) had up to 3 visits audiotape recorded. The audiotapes were transcribed
      to facilitate content analysis. Four patients with RA who did not participate in
      the original study guided development of the coding scheme and used it to code
      the transcripts. RESULTS: The coding scheme contains 14 gist themes centering on
      medication effectiveness, need, and safety. There was considerable variation
      among the gist coders in the specific themes they extracted from individual
      transcripts. We observed the greatest intercoder agreement for the 4 gist theme
      variables related to whether the rheumatologist wanted to make changes to the
      medication regimen. Furthermore, the coders rarely used the "not clear" category
      to code these 4 variables. In contrast, intercoder agreement for the remaining
      gist themes, which were designed to capture issues central to the communication
      of information about medication risks and benefits, was low and the "not clear"
      category was used more frequently. CONCLUSION: Our study findings suggest that
      different people exposed to the same information may form different gist
      representations. Patient-provider communication concerning medication risks and
      benefits might be enhanced by better understanding the factors that influence the
      gist extraction process.

PMID- 24022873
TI  - Initial psychometric evaluation of the Moral Injury Questionnaire--Military
      version.
AB  - Moral injury is an emerging construct related to negative consequences associated
      with war-zone stressors that transgress military veterans' deeply held
      values/beliefs. Given the newness of the construct, there is a need for
      instrumentation that might assess morally injurious experiences (MIEs) in this
      population. Drawing on a community sample of 131 Iraq and/or Afghanistan Veterans
      and clinical sample of 82 returning Veterans, we conducted an initial
      psychometric evaluation of the newly developed Moral Injury Questionnaire
      Military version (MIQ-M)-a 20-item self-report measure for assessing MIEs.
      Possibly due to low rates of reporting, an item assessing sexual trauma did not
      yield favourable psychometric properties and was excluded from analyses. Veterans
      in the clinical sample endorsed significantly higher scores across MIQ-M items.
      Factor analytic results for the final 19 items supported a unidimensional
      structure, and convergent validity analyses revealed that higher scores
      (indicative of more MIEs) were correlated with greater general combat exposure,
      impairments in work/social functioning, posttraumatic stress and depression in
      the community sample. In addition, when controlling for demographics, deployment
      related factors and exposure to life threat stressors associated with combat,
      tests of incremental validity indicated that MIQ-M scores were also uniquely
      linked with suicide risk and other mental health outcomes. These findings provide
      preliminary evidence for the validity of the MIQ-M and support the applicability
      of this measure for further research and clinical work with Veterans. KEY
      PRACTITIONER MESSAGE: Military service can confront service members with
      experiences that undermine their core sense of humanity and violate global values
      and beliefs. These types of experiences increase the risk for posttraumatic
      maladjustment in this population, even when accounting for rates of exposure to
      life threat traumas. Moral injury is an emerging construct to more fully capture
      the many possible psychological, ethical, and spiritual/existential challenges
      among persons who served in modern wars and other trauma-exposed professional
      groups. There is currently a need for psychometrically sound instrumentation for
      assessing morally injurious experiences (MIEs). The Moral Injury Questionnaire -
      Military Version (MIQ-M) was developed to provide a tool for assessing possible
      MIEs among military populations. This study provides preliminary evidence of the
      validity - including factorial, concurrent, and incremental - and clinical
      utility of the MIQ-M for further applications in clinical and research contexts.

PMID- 24022875
TI  - Genetic variant of AKT1 and AKTIP associated with late-onset depression in a
      Brazilian population.
AB  - OBJECTIVES: Examine the association between polymorphisms in the AKT1 and AKTIP
      genes and late-onset depression (LOD). Major depressive disorder is one of the
      most prevalent neuropsychiatric diseases. LOD is a disorder that starts after 65
      years old. AKT1 is a downstream enzyme that has been implicated in the
      pathogenesis of neurotransmitter-related disorders, such as depression. The
      identification of a novel AKT1-binding protein (AKTIP) was pointed as an
      important new target. AKTIP binds directly to AKT1, enhancing the phosphorylation
      of regulatory sites, and this modulation are affected by AKT1 activation. The
      association of AKT1 and AKTIP polymorphisms with depressive symptoms was not
      investigated in LOD. DESIGN: Genotype tagSNPs in the AKT1 and AKTIP in LOD
      patients and controls. SETTINGS: An academic medical center. PARTICIPANTS: Sample
      composed by 190 outpatients with LOD and 77 healthy individuals. MEASURES: The
      participants were evaluated using Diagnostic and Statistical Manual IV criteria,
      MINI-PLUS and the Geriatric Depression Scale. RESULTS: Our findings suggested an
      association between the tagSNP rs3730358 homozygous A/A (p = 0.006) and LOD. A
      strong association of allele A and increased association for LOD was demonstrated
      with tagSNP rs3730358 (p-value = 0.003). LIMITATIONS: Limitation include
      composition of our control group, where the exclusion criteria generated a kind
      of super-healthy older group what might have produced a hidden stratification
      when compared with the LOD. CONCLUSION: This study is the first one to establish
      the association of the AKT1/AKTIP genes and LOD, and further studies are
      necessary to clarify the functional role of these proteins.

PMID- 24022874
TI  - Nonsyndromic brachydactyly type D and type E mapped to 7p15 in healthy children
      and adults from the Jirel ethnic group in eastern Nepal.
AB  - OBJECTIVES: There is phenotypic overlap between Brachydactyly Type D (BDD) and
      Brachydactyly Type E (BDE) that suggests a possible common underlying etiology.
      We seek to understand the genetic underpinnings of, and relationship between,
      these skeletal anomalies. METHODS: The Jirel ethnic group of eastern Nepal
      participates in various genetic epidemiologic studies, including those in which
      hand-wrist radiographs have been taken to examine skeletal development. Nearly
      2,130 individuals (969 males; 1,161 females) were phenotyped for BDD/BDE. Of
      these, 1,722 individuals (773 males; 949 females) were genotyped for 371 STR
      markers spanning the autosomal genome. Variance components-based linkage analysis
      was used to conduct a genome-wide linkage scan for QTL influencing the BDD/BDE
      phenotype. RESULTS: BDD was present in 3.55%, and BDE was present in 0.39%, of
      the study sample. Because of the phenotypic overlap between two traits, affecteds
      of either type were considered as affected by a single combined phenotype
      (BDD/BDE) having a prevalence of 3.94%. The additive genetic heritability of
      BDD/BDE was highly significant (h(2) +/- SE = 0.89 +/- 0.13; P = 1.7 * 10(-11) ).
      Significant linkage of BDD/BDE was found to markers on chromosome 7p21-7p14 (peak
      LOD score = 3.74 at 7p15 between markers D7S493 and D7S516). CONCLUSIONS:
      Possible positional candidate genes in the one-lod support interval of this QTL
      include TWIST and the HOXA1-A13 cluster. This is the first study to report
      significant linkage results for BDD/BDE using a large extended pedigree, and the
      first to suggest that mutations in TWIST and/or the HOXA1-A13 cluster may
      contribute to these specific skeletal anomalies.

PMID- 24022876
TI  - Atherosclerotic cardiovascular disease in hospitalized patients with systemic
      sclerosis: higher mortality than patients with lupus and rheumatoid arthritis.
AB  - OBJECTIVE: Systemic sclerosis (SSc; scleroderma) patients have an increased risk
      for atherosclerotic cardiovascular disease (ASCVD), possibly mediated through
      inflammatory and fibrotic mechanisms affecting the macrovasculature and
      microvasculature. We utilized the US Nationwide Inpatient Sample to assess the
      frequency of and mortality risk associated with ASCVD among hospitalized SSc
      patients. METHODS: We examined the frequency and mortality associated with
      primary diagnoses and procedures related to ASCVD among adult SSc patients using
      data from 1993 to 2007. Using multivariate logistic regression (controlling for
      age, sex, nonelective admission, and modified Charlson Comorbidity Index), we
      compared the odds of death among hospitalized SSc patients with ASCVD to those
      with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), as well as
      to a control group that excluded patients with connective tissue diseases.
      RESULTS: A total of 308,452 hospitalizations of SSc patients were included, of
      which 5.4% were associated with a primary ASCVD diagnosis or procedure. ASCVD
      related SSc hospitalizations were more likely to result in death compared with
      non-ASCVD SSc hospitalizations (odds ratio [OR] 1.3, 95% confidence interval [95%
      CI] 1.1-1.4). Multivariate analyses showed that ASCVD-related SSc
      hospitalizations were more likely to result in death than similar
      hospitalizations of SLE (OR 1.5, 95% CI 1.2-1.8), RA (OR 2.3, 95% CI 1.9-2.8),
      and control patients (OR 1.4, 95% CI 1.2-1.8) with ASCVD. CONCLUSIONS: SSc
      patients with ASCVD have higher in-hospital mortality than comparable groups of
      SLE and RA patients with ASCVD. Further research to elucidate the specific
      mechanisms underlying ASCVD in SSc is necessary.

PMID- 24022877
TI  - Level and appraisal of fatigue are not specific in burnout.
AB  - Fatigue is a main feature of the burnout syndrome but also very common in other
      psychiatric disorders such as major depression and anxiety disorders. This raises
      the question of whether the level and appraisal of fatigue is experienced
      differently by individuals suffering from burnout than by those exhibiting
      anxiety disorders and major depression. If fatigue is experienced differently in
      burnout compared with other disorders, this may clarify why fatigue is the main
      feature of the burnout syndrome. This knowledge may lead to the application of
      specific therapeutic interventions aimed at the experience of fatigue in burnout.
      In the present study, we investigated whether fatigue is experienced differently
      in burnout patients than in patients suffering from anxiety disorders or major
      depression. We presented 73 burnout patients, 67 depressed patients, 57 patients
      with an anxiety disorder and 127 healthy participants with a rating scale
      containing statements about the fatigue-performance relationship, and we assessed
      the level of fatigue, depression and anxiety. The level of fatigue reported by
      burnout patients was high but did not differ from that of the other patient
      groups. The appraisal of fatigue also did not differ among the patient groups.
      The burnout patients did not appraise their fatigue as a result of unrewarding
      activities nor did they catastrophize fatigue in an exceptional way. Thus, the
      level of fatigue and the appraisal of fatigue may be less relevant to the
      understanding of the specific pathological processes associated with burnout than
      is often presumed.

PMID- 24022878
TI  - Prevalence of multidrug-resistant Pseudomonas aeruginosa and carbapenem-resistant
      Enterobacteriaceae among specimens from hospitalized patients with pneumonia and
      bloodstream infections in the United States from 2000 to 2009.
AB  - BACKGROUND: Antimicrobial resistance complicates antibiotic selection.
      Pseudomonas aeruginosa (PA), common in pneumonia and blood stream infections
      (BSIs), is frequently resistant to multiple antimicrobial classes. Carbapenem
      resistant Enterobacteriaceae (CRE) have emerged as a pathogen of concern over the
      past decade. OBJECTIVE: To determine the prevalence of CRE and multidrug
      resistant PA (MDR-PA) in pneumonia and BSI hospitalizations. DESIGN: Survey of
      data from a nationally representative sample of microbiology laboratories in 217
      hospitals in the United States. METHODS/SETTING: We examined Eurofins' The
      Surveillance Network database from 2000 to 2009 to explore the proportion of all
      PA in pneumonia and BSI that is MDR. We performed the same analysis for CRE as a
      proportion of Enterobacteriaceae. We defined MDR-PA as any isolate resistant to
      >=3 drug classes. Enterobacteriaceae were CRE if resistant to both a third
      generation cephalosporin and a carbapenem. RESULTS: We identified 205,526 PA
      (187,343 pneumonia; 18,183 BSI) and 95,566 Enterobacteriaceae specimens (58,810
      pneumonia; 36,756 BSI). The prevalence of MDR-PA was ~15-fold higher than CRE in
      both infection types (pneumonia: 22.0% MDR-PA vs 1.6% CRE; BSI: 14.7% MDR-PA vs
      1.1% CRE). There was a net rise in MDR-PA as a proportion of all PA from 2000 to
      2009 (BSI: 10.7%-13.5%; pneumonia: 19.2%-21.7%). The CRE phenotype emerged in
      2002 in both infection types, peaking in 2008 at 3.6% in BSI and 5.3% in
      pneumonia, and stabilized thereafter. CONCLUSIONS: Although CRE organisms have
      emerged as an important pathogen in BSI and pneumonia, MDR-PA remains more
      prevalent in the United States.

PMID- 24022879
TI  - Cross validation of ROC generated thresholds for field assessed aerobic fitness
      related to weight status and cardiovascular disease risk in Portuguese young
      people.
AB  - OBJECTIVES: To examine the efficacy of aerobic fitness thresholds in predicting
      weight status and cardiovascular disease risk (CVD) in young people. METHODS: A
      cross-sectional school-based study was conducted on 414 Portuguese young people
      (235 girls and 179 boys) aged 10-16 years (Mean age +/- SD = 13.6 +/- 1. 8
      years). Height and mass were assessed to determine body mass index (BMI). The 20
      m multistage shuttle-fitness test (MSFT) was used as an estimate of aerobic
      fitness. Capillary blood sampling was used to determine: total cholesterol,
      triglycerides, high-, and low-density lipoprotein. These were combined with
      measures of systolic blood pressure as z-scores and summed to create a CVD risk
      score. RESULTS: Analysis of covariance, controlling for sexual maturation,
      indicated a significant main effect for BMI as a result of fitness category (P =
      0.0001). When applied to CVD risk data, there was no difference between "fit" and
      "unfit" groups (P = 0.136). Subsequent receiver operating curve (ROC) analysis
      indicated significant diagnostic accuracy of 20 mMSFT performance for boys and
      girls (both P = 0.0001) with subsequent cut-offs of estimated VO2 peak of 49.5 ml
      kg(-1) min(-1) for girls and 47.7 ml kg(-1) min(-1) for boys. When applied to BMI
      and CVD risk data, there was a significant main effect as a result of fitness
      category for BMI (P = 0.0001) and CVD risk score (P = 0.0001). CONCLUSIONS:
      Recently established cut-points proposed by Boddy et al. (Boddy et al. [2012]:
      PLoS One 7(9): e45755) show validity in distinguishing between weight status but
      not CVD risk in Portuguese young people. Alternative ROC generated cut points
      significantly predicted BMI and CVD risk in this sample.

PMID- 24022880
TI  - Extralobar pulmonary sequestration with combined gastric and intradiaphragmatic
      locations.
AB  - Extralobar pulmonary sequestration is a congenital lung malformation
      characterized by a non-functional lung segment with systemic feeding vessel. Over
      90% of sequestrations are found in the thorax with less than 10% located in the
      abdomen. We present an unusual case of intra abdominal pulmonary sequestration,
      located suprarenally, adherent to both the stomach and the diaphragm. The
      malformation was surgically excised via laparoscopy in the second year of life,
      when no evidence of regression was found on follow up imaging. On the occasion of
      this description, the spectrum of bronchopulmonary foregut malformation is
      discussed.

PMID- 24022881
TI  - Threats and opportunities for freshwater conservation under future land use
      change scenarios in the United States.
AB  - Freshwater ecosystems provide vital resources for humans and support high levels
      of biodiversity, yet are severely threatened throughout the world. The expansion
      of human land uses, such as urban and crop cover, typically degrades water
      quality and reduces freshwater biodiversity, thereby jeopardizing both
      biodiversity and ecosystem services. Identifying and mitigating future threats to
      freshwater ecosystems requires forecasting where land use changes are most
      likely. Our goal was to evaluate the potential consequences of future land use on
      freshwater ecosystems in the coterminous United States by comparing alternative
      scenarios of land use change (2001-2051) with current patterns of freshwater
      biodiversity and water quality risk. Using an econometric model, each of our land
      use scenarios projected greater changes in watersheds of the eastern half of the
      country, where freshwater ecosystems already experience higher stress from human
      activities. Future urban expansion emerged as a major threat in regions with high
      freshwater biodiversity (e.g., the Southeast) or severe water quality problems
      (e.g., the Midwest). Our scenarios reflecting environmentally oriented policies
      had some positive effects. Subsidizing afforestation for carbon sequestration
      reduced crop cover and increased natural vegetation in areas that are currently
      stressed by low water quality, while discouraging urban sprawl diminished urban
      expansion in areas of high biodiversity. On the other hand, we found that
      increases in crop commodity prices could lead to increased agricultural threats
      in areas of high freshwater biodiversity. Our analyses illustrate the potential
      for policy changes and market factors to influence future land use trends in
      certain regions of the country, with important consequences for freshwater
      ecosystems. Successful conservation of aquatic biodiversity and ecosystem
      services in the United States into the future will require attending to the
      potential threats and opportunities arising from policies and market changes
      affecting land use. 

PMID- 24022883
TI  - Does subclinical atherosclerosis really exist in systemic sclerosis? Comment on
      the article by Turiel et al.

PMID- 24022882
TI  - Reduced cerebral perfusion predicts greater depressive symptoms and cognitive
      dysfunction at a 1-year follow-up in patients with heart failure.
AB  - OBJECTIVE: Cerebral hypoperfusion is common in heart failure (HF) and believed to
      underlie poor neurocognitive outcomes in this population. Up to 42% of HF
      patients also exhibit depressive symptomatology that may stem from reduced
      cerebral blood flow. However, no study has examined this possibility or whether
      reduced brain perfusion increases risk for future cognitive dysfunction in older
      adults with HF. METHODS: One hundred HF patients underwent transcranial Doppler
      ultrasonagraphy to quantify global cerebral blood flow velocity (CBF-V) and were
      administered a cognitive test battery to assess global cognition,
      attention/executive function, and memory abilities. All participants then
      completed the Beck Depression Inventory-II to assess depressive symptomatology.
      These procedures were performed at baseline and at 12-month follow-up. RESULTS:
      Repeated measures revealed that CBF-V declined over the 12-month period.
      Regression analyses showed that reduced baseline CBF-V predicted worse
      performances in attention/executive function (p < 0.05 for all) and a trend for
      memory (p = 0.09) in addition to greater depressive symptomatology (p < 0.05) at
      the 12-month follow-up, even after controlling for baseline factors and medical
      and demographic variables. CONCLUSIONS: Cerebral perfusion declined over time and
      was associated with poorer cognitive function and greater depressive symptoms at
      a 1-year follow-up in HF. Prospective studies with long-term follow-ups that
      employ neuroimaging are needed to examine whether cognitive dysfunction and
      depression in HF stem from the adverse effects of cerebral hypoperfusion on the
      cerebral structure.

PMID- 24022885
TI  - Rooibos influences glucocorticoid levels and steroid ratios in vivo and in vitro:
      a natural approach in the management of stress and metabolic disorders?
AB  - SCOPE: To determine the effect of Rooibos (Aspalathus linearis) on glucocorticoid
      biosynthesis and inactivation in vivo and in vitro. METHODS AND RESULTS: Ultra
      performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) analyses
      of in vivo studies showed that human Rooibos consumption increased cortisone
      plasma levels in males (p = 0.0465) and reduced cortisol:cortisone ratios in
      males and females (p = 0.0486) at risk for cardiovascular disease. In rats,
      corticosterone (CORT) (p = 0.0275) and deoxycorticosterone (p = 0.0298) levels as
      well as the CORT:testosterone ratio (p = 0.0009) decreased following Rooibos
      consumption. The inactivation of cortisol was investigated in vitro by expressing
      11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) and type 2 (11betaHSD2)
      in CHO-K1 cells. Rooibos inhibited 11betaHSD1, which resulted in a significant
      reduction in the cortisol:cortisone ratio (p < 0.01). No significant effect was
      detected on 11betaHSD2. In vitro studies in adrenal H295R cells showed that
      Rooibos and rutin, one of the more stable flavonoid compounds present in Rooibos,
      significantly reduced the levels of cortisol and CORT in cells stimulated with
      forskolin to mimic a stress response. CONCLUSION: In vivo studies demonstrate
      that Rooibos significantly decreased glucocorticoid levels in rats and steroid
      metabolite ratios linked to metabolic disorders--cortisol:cortisone in humans and
      CORT:testosterone in rats. Results obtained at cellular level elucidate possible
      mechanisms by which these effects were achieved.

PMID- 24022884
TI  - Expression of podocalyxin separates the hematopoietic and vascular potentials of
      mouse embryonic stem cell-derived mesoderm.
AB  - In the mouse embryo and differentiating embryonic stem cells, the hematopoietic,
      endothelial, and cardiomyocyte lineages are derived from Flk1+ mesodermal
      progenitors. Here, we report that surface expression of Podocalyxin (Podxl), a
      member of the CD34 family of sialomucins, can be used to subdivide the Flk1+
      cells in differentiating embryoid bodies at day 4.75 into populations that
      develop into distinct mesodermal lineages. Definitive hematopoietic potential was
      restricted to the Flk1+Podxl+ population, while the Flk1-negative Podxl+
      population displayed only primitive erythroid potential. The Flk1+Podxl-negative
      population contained endothelial cells and cardiomyocyte potential. Podxl
      expression distinguishes Flk1+ mesoderm populations in mouse embryos at days 7.5,
      8.5, and 9.5 and is a marker of progenitor stage primitive erythroblasts. These
      findings identify Podxl as a useful tool for separating distinct mesodermal
      lineages.

PMID- 24022887
TI  - Galea Responds to "consequential(ist) epidemiology: finally".

PMID- 24022886
TI  - Patterns of senescence in human cardiovascular fitness: VO2 max in subsistence
      and industrialized populations.
AB  - OBJECTIVES: This study explores whether cardiovascular fitness levels and
      senescent decline are similar in the Tsimane of Bolivia and Canadians, as well as
      other subsistence and industrialized populations. Among Tsimane, we examine
      whether morbidity predicts lower levels and faster decline of cardiovascular
      fitness, or whether their lifestyle (e.g., high physical activity) promotes high
      levels and slow decline. Alternatively, high activity levels and morbidity might
      counterbalance such that Tsimane fitness levels and decline are similar to those
      in industrialized populations. METHODS: Maximal oxygen uptake (VO2 max) was
      estimated using a step test heart rate method for 701 participants. We compared
      these estimates to the Canadian Health Measures Survey and previous studies in
      industrialized and subsistence populations. We evaluated whether health
      indicators and proxies for market integration were associated with VO2 max levels
      and rate of decline for the Tsimane. RESULTS: The Tsimane have significantly
      higher levels of VO2 max and slower rates of decline than Canadians; initial
      evidence suggests differences in VO2 max levels between other subsistence and
      industrialized populations. Low hemoglobin predicts low VO2 max for Tsimane women
      while helminth infection predicts high VO2 max for Tsimane men, though results
      might be specific to the VO2 max scaling parameter used. No variables tested
      interact with age to moderate decline. CONCLUSIONS: The Tsimane demonstrate
      higher levels of cardiovascular fitness than industrialized populations, but
      levels similar to other subsistence populations. The high VO2 max of Tsimane is
      consistent with their high physical activity and few indicators of cardiovascular
      disease, measured in previous studies.

PMID- 24022888
TI  - Invited commentary: consequential(ist) epidemiology: let's seize the day.
AB  - Now is the time for the science of epidemiology to embrace its pragmatic roots.
      The article by Galea in this issue of the Journal (Am J Epidemiol.
      2013;178(8):1185-1191) calls for us to become more "consequentialist." The
      Affordable Care Act allows us to access population-level databases from which we
      can examine how to deliver care more efficiently and cost-effectively. Asking the
      questions "so what" and "how much" will increase our relevance over the next
      decade. 

PMID- 24022889
TI  - Snippets from the past: the evolution of Wade Hampton Frost's epidemiology as
      viewed from the American Journal of Hygiene/Epidemiology.
AB  - Wade Hampton Frost, who was a Professor of Epidemiology at Johns Hopkins
      University from 1919 to 1938, spurred the development of epidemiologic methods.
      His 6 publications in the American Journal of Hygiene, which later became the
      American Journal of Epidemiology, comprise a 1928 Cutter lecture on a theory of
      epidemics, a survey-based study of tonsillectomy and immunity to Corynebacterium
      diphtheriae (1931), 2 papers from a longitudinal study of the incidence of minor
      respiratory diseases (1933 and 1935), an attack rate ratio analysis of the
      decline of diphtheria in Baltimore (1936), and a 1936 lecture on the age, time,
      and cohort analysis of tuberculosis mortality. These 6 American Journal of
      Hygiene /American Journal of Epidemiology papers attest that Frost's personal
      evolution mirrored that of the emerging "early" epidemiology: The scope of
      epidemiology extended beyond the study of epidemics of acute infectious diseases,
      and rigorous comparative study designs and their associated quantitative methods
      came to light. 

PMID- 24022890
TI  - An argument for a consequentialist epidemiology.
AB  - Epidemiology is the study of the causes and distributions of diseases in human
      populations so that we may identify ways to prevent and control disease. Although
      this definition broadly serves us well, I suggest that in recent decades, our
      discipline's robust interest in identifying causes has come at the expense of a
      more rigorous engagement with the second part of our vision for ourselves-the
      intent for us to intervene-and that this approach threatens to diminish our
      field's relevance. I argue here for a consequentialist epidemiology, a
      formalization and recalibration of the philosophical foundations of our
      discipline. I discuss how epidemiology is, at its core, more comfortably a
      consequentialist, as opposed to a deontological, discipline. A more
      consequentialist approach to epidemiology has several implications. It clarifies
      our research priorities, offers a perspective on the place of novel epidemiologic
      approaches and a metric to evaluate the utility of new methods, elevates the
      importance of global health and considerations about equity to the discipline,
      brings into sharp focus our engagement in implementation and translational
      science, and has implications for how we teach our students. I intend this
      article to be a provocation that can help clarify our disciplinary intentions. 

PMID- 24022891
TI  - Stochastic structure determination for conformationally flexible heterogenous
      molecular clusters: application to ionic liquids.
AB  - We present a novel method that enables accurate and efficient computational
      determination of conformationally flexible clusters, "Kick(3)" This method uses
      stochastically generated structures in combination with fast quantum mechanical
      methods. We demonstrate the power of this method by elucidating the structure of
      ionic liquid (IL) ([xMIM(+)][NO3(-)])n clusters (x = E, B, D, n = 1-10,15).
      Dispersion-corrected, third-order self-consistent-charge density-functional tight
      binding (DFTB3) is shown to be a computationally efficient, yet reliable
      approximation to density functional theory for predicting and understanding IL
      structure and stability. The presented approach, therefore, enables the accurate
      and efficient screening of ILs with high potential toward practical applications,
      without recourse to more expensive quantum chemical methods.

PMID- 24022892
TI  - Substantial reorganization of China's tropical and subtropical forests: based on
      the permanent plots.
AB  - There is evidence that climate change induced tree mortalities in boreal and
      temperate forests and increased forest turnover rates (both mortality and
      recruitment rates) in Amazon forests. However, no study has examined China's
      tropical and subtropical evergreen broadleaved forests (TEBF) that cover >26% of
      China's terrestrial land. The sustainability of this biome is vital to the
      maintenance of local ecosystem services (e.g., carbon sequestration, biodiversity
      conservation, climatic regulation), many of which may influence patterns of
      atmospheric circulation and composition at regional to global scales. Here, we
      analyze time-series data collected from thirteen permanent plots within China's
      unmanaged TEBF to study whether and how this biome has changed over recent
      decades. We find that the numbers of individuals and species for shrub and small
      tree have increased since 1978, whereas the numbers of individuals and species
      for tree have decreased over this same time period. The shift in species
      composition is accompanied by a decrease in the mean diameter at breast height
      (DBH) for all individuals combined. China's TEBF may thereby be transitioning
      from cohorts of fewer and larger individuals to ones of more and smaller
      individuals, which shows a unique change pattern differing from the documented.
      Regional-scale drying is likely responsible for the biome's reorganization. This
      biome-wide reconstitution would deeply impact the regimes of carbon sequestration
      and biodiversity conservation and have implications for the sustainability of
      economic development in the area. 

PMID- 24022893
TI  - Reply: To PMID 22899452.

PMID- 24022894
TI  - Trajectories of cognitive decline by driving mobility: evidence from the Health
      and Retirement Study.
AB  - OBJECTIVE: The recent emphasis of the importance of "aging in place" has
      highlighted the role of transportation in health promotion over the life course.
      Driving cessation in later life is associated with numerous poor health outcomes
      including limitations in social and physical functioning and increased risk of
      mortality. However, little is known about the relationship between driving
      cessation and change in cognitive functioning in late life. This study examined
      the association between driving mobility and trajectories of cognitive
      functioning among older adults. METHODS: Using data from six waves [1998-2008] of
      the Health and Retirement Study, trajectories of cognitive functioning were
      estimated over a 10-year period using longitudinal mixed effects models [N =
      9,135]. Cognitive function was assessed with a modified version of the Telephone
      Interview for Cognitive Status. Driving status and health characteristics were
      assessed by self-report. RESULTS: Older adults who did not drive (former and
      never drivers) at baseline had lower average cognitive scores compared with
      active drivers. Former drivers had accelerated cognitive decline over the
      subsequent 10 years compared with active drivers (beta = -0.35, 95% Confidence
      Interval [CI] = -0.43 to -0.26) even after controlling for baseline cognitive
      functioning and health status. The transition to non-driving was associated with
      a faster cognitive decline among those who were driving at baseline (beta = 
      0.31, 95% CI = -0.40 to -0.22). CONCLUSIONS: Older adults without driving
      mobility had poorer cognitive functioning at baseline and experienced accelerated
      cognitive decline relative to active drivers over follow-up.

PMID- 24022897
TI  - Biliary stent migration causing perforation of the caecum and chronic abdominal
      pain.
AB  - We report a case of biliary stent migration causing perforation of the caecum and
      presenting as chronic abdominal pain. The case was managed by colonoscopic
      removal of the stent. 

PMID- 24022896
TI  - Electrostatic control of structure in self-assembled membranes.
AB  - Self-assembling peptide amphiphiles (PAs) can form hierarchically ordered
      membranes when brought in contact with aqueous polyelectrolytes of the opposite
      charge by rapidly creating a diffusion barrier composed of filamentous
      nanostructures parallel to the plane of the incipient membrane. Following this
      event, osmotic forces and charge complexation template nanofiber growth
      perpendicular to the plane of the membrane in a dynamic self-assembly process. In
      this work, we show that this hierarchical structure requires massive interfacial
      aggregation of PA molecules, suggesting the importance of rapid diffusion barrier
      formation. Strong PA aggregation is induced here through the use of heparin
      binding PAs with heparin and also with polyelectrolytes of varying charge
      density. Small angle X-ray scattering shows that in the case of weak PA
      polyelectrolyte interaction, membranes formed display a cubic phase ordering on
      the nanoscale that likely results from clusters of PA nanostructures surrounded
      by polyelectrolyte chains. 

PMID- 24022898
TI  - Living without left atrium.

PMID- 24022895
TI  - The RNA-binding protein Musashi-1 regulates proteasome subunit expression in
      breast cancer- and glioma-initiating cells.
AB  - Cancer stem cells (CSCs) or tumor-initiating cells, similar to normal tissue stem
      cells, rely on developmental pathways, such as the Notch pathway, to maintain
      their stem cell state. One of the regulators of the Notch pathway is Musashi-1, a
      mRNA-binding protein. Musashi-1 promotes Notch signaling by binding to the mRNA
      of Numb, the negative regulator of Notch signaling, thus preventing its
      translation. CSCs have also been shown to downregulate their 26S proteasome
      activity in several types of solid tumors, thus making them resistant to
      proteasome-inhibitors used as anticancer agents in the clinic. Interestingly, the
      Notch pathway can be inhibited by proteasomal degradation of the Notch
      intracellular domain (Notch-ICD); therefore, downregulation of the 26S proteasome
      activity can lead to stabilization of Notch-ICD. Here, we present evidence that
      the downregulation of the 26S proteasome in CSCs constitutes another level of
      control by which Musashi-1 promotes signaling through the Notch pathway and
      maintenance of the stem cell phenotype of this subpopulation of cancer cells. We
      demonstrate that Musashi-1 mediates the downregulation of the 26S proteasome by
      binding to the mRNA of NF-YA, the transcriptional factor regulating 26S
      proteasome subunit expression, thus providing an additional route by which the
      degradation of Notch-ICD is prevented, and Notch signaling is sustained.

PMID- 24022899
TI  - Successful treatment of extensive cerebral venous sinus thrombosis using a
      combined approach with Penumbra aspiration system and Solitaire FR retrieval
      device.
AB  - We present a young woman with rapidly progressive neurologic decline in the
      setting of malignant cerebral edema due to extensive superior sagittal sinus
      thrombosis and cortical venous thrombosis despite intravenous heparin
      administration. Complete revascularization of the occluded sinus was achieved
      using suction thrombectomy with the 5 max Penumbra catheter in combination with
      the Solitaire FR clot retrieval device. The successful endovascular treatment
      halted the progression of her cerebral edema, and the patient eventually had an
      excellent recovery after prolonged intensive medical therapy. To our knowledge,
      this is the first reported case describing such a combined mechanical approach
      for cerebral venous sinus thrombosis. The clot retrieval properties of the
      Solitaire device combined with direct aspiration via the newest generation
      Penumbra catheters may allow more rapid, safe and efficient revascularization
      than all previously reported endovascular treatments for this potentially
      devastating condition.

PMID- 24022900
TI  - Bilateral tubo-ovarian abscess and sepsis caused by Salmonella in patients with
      systemic lupus erythematosus.

PMID- 24022901
TI  - Stretching the indications: high tibial osteotomy used successfully to treat
      isolated ankle symptoms.
AB  - High tibial osteotomy (HTO) is successful in treating symptomatic varus arthritis
      of the knee. We present a case where ankle pain and instability were attributed
      to varus ankle malalignment. This was found to be secondary to constitutional
      varus of the proximal tibia but the patient's knee was asymptomatic. The decision
      to operate on an asymptomatic knee in the hope of improving ankle symptoms took a
      period of careful consideration, planning and discussion. HTO was performed
      without immediate complication and the patient reported an excellent outcome with
      marked improvement in Mazur's foot and ankle score from 18 to 85. In well
      selected and planned cases, HTO may be considered as an instrument of deformity
      correction with improvement in symptoms from joints distant to the surgical site.

PMID- 24022902
TI  - Coexistence of scleroderma with multiple myeloma: a rare association.
AB  - Coexistence of scleroderma with multiple myeloma (MM) is an unusual finding with
      unclear significance. Only 13 cases of MM with scleroderma have been reported
      until now. We report a case of a 24-year-old man with 8-year history of
      progressive thickening of skin all over the body. Histopathology of skin lesion
      was consistent with scleroderma. Bone marrow biopsy showed interstitial and focal
      increase in plasma cells and increased bone marrow fibrosis. Skeletal survey
      showed osteopenia, but no osteolytic lesion or fracture. The patient was
      diagnosed as scleroderma with coexistence of immunoglobulin A, kappaMM. The
      patient recovered with improvement of skin lesions after 9 months of therapy with
      thalidomide and dexamethasone.

PMID- 24022903
TI  - Shiga toxin producing E coli bloodstream infection secondary to Strongyloides
      penetration through intestinal mucosa.
AB  - A 51-year-old woman with diabetes, who immigrated to the USA 22 years ago from
      Laos, was admitted to the hospital for evaluation of fever, abdominal pain,
      vomiting and diarrhoea. A workup for acute gastroenteritis revealed a positive
      stool PCR for Shiga toxin-producing Escherichia coli. Two sets of blood cultures
      drawn at admission were positive for E coli. A review of her previous medical
      records revealed the presence of eosinophilia, up to 20%, 14 years prior to that
      was never investigated. Therefore, stool samples were examined and two of three
      specimens were positive for Strongyloides stercoralis larvae, confirming the
      diagnosis of Strongyloides hyperinfection syndrome.

PMID- 24022904
TI  - Shaking head means "no".
AB  - A 45-year-old man was admitted to the emergency department because of twitching
      of the head. The patient took a tablet of sumatriptan every 3-4 h because of
      increasing head pain after a car accident. Owing to depression, the patient was
      on long-term treatment with venlafaxine. The patient presented as hypertensive,
      tachycardic, with dyskinesia and spontaneous myoclonic movements of the right
      sternocleidomastoid muscle. In a CT scan of the head and cervical spine any
      fractures, bleeding or damage of the vessels after the accident could be ruled
      out. After discontinuation of all serotonergic agents, administration of
      lorazepam symptoms resolved 24 h after the last intake of sumatriptan. Serotonin
      syndrome is a clinical diagnosis, which requires a high-index of diagnostic
      suspicion. Clinical features include a broad spectrum of symptoms ranging from
      mild to life-threatening manifestations. Management is based on removal of
      precipitating drugs and symptomatic care including benzodiazepines.

PMID- 24022905
TI  - Long-lasting response to crizotinib in brain metastases due to EML4-ALK
      rearranged non-small-cell lung cancer.
AB  - Anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC) is
      highly responsive to crizotinib, an oral ATP-competitive selective inhibitor of
      ALK. However, crizotinib exhibits extremely poor blood-brain barrier penetration;
      therefore, it is considered to play a limited role in the treatment of brain
      metastases. We present a case of a 50-year-old man with a diagnosis of ALK
      rearranged NSCLC with brain metastasis and malignant pleural effusion. Despite
      the several systemic chemotherapy regimens and whole brain radiotherapy, brain
      metastasis was refractory; therefore, crizotinib was initiated. A CT scan showed
      a slight reduction in the brain metastasis and no change in intrathoracic disease
      17 weeks after initiating crizotinib. Moreover, CT obtained 12 months after
      crizotinib treatment revealed brain metastasis without progression. To our
      knowledge, the present case is the second report of crizotinib-responsive brain
      metastases due to echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK)
      rearranged NSCLC.

PMID- 24022906
TI  - Cytomegalovirus-induced colonic stricture presenting as acute intestinal
      obstruction in an immunocompetent adult.
AB  - Cytomegalovirus (CMV) infection causes significant morbidty and mortality in
      immunopromised patients. Though it is usually silent in immunocompetent adults,
      rarely it can cause serious life-threatening complications. Gastrointestinal
      tract is one of the commonly involved organs, where it produces a spectrum of
      clinical manifestation ranging from mild non-specific abdominal pain and
      diarrhoea to severe infection with toxic megacolon and death. We present a 65
      year-old immunocompetent male patient admitted with acute colonic obstruction
      secondary to CMV-induced colonic stricture, highlighting the importance of
      considering it as a differential diagnosis for colonic obstruction and reviewing
      its management.

PMID- 24022907
TI  - Acquired esophagobronchial fistula without Ono's sign and with unusual cause.
AB  - A 60-year-old woman presented with dyspnoea and respirophasic chest discomfort,
      as well as a history of idiopathic oesophageal diverticulum. Physical
      examinations showed no evidence of Ono's sign, fever and weight loss. Chest
      radiograph revealed a right-sided transudative pleural effusion. Barium
      oesophagogram made a diagnosis of acquired esophagobronchial fistula
      communicating between oesophagus and bronchus. The oesophagobronchial fistula,
      causing pleural effusions, was very small and could be caused by idiopathic
      oesophageal diverticulum. The pleural effusion was removed by thoracentesis,
      which improved her symptoms. Surgical therapy or covered oesophageal stenting was
      advised, but she declined. She is followed-up regularly on an outpatient basis.

PMID- 24022908
TI  - Giant cerebellopontine angle schwannoma in a child.

PMID- 24022909
TI  - Reply: To PMID 23536356.

PMID- 24022910
TI  - Cross cultural analysis of factors associated with age at natural menopause among
      Latin-American immigrants to Madrid and their Spanish neighbors.
AB  - OBJECTIVES: In this study, age at menopause was examined in relation to
      demographic and life style factors among Latin-American immigrants to Madrid and
      their Spanish counterparts. METHODS: Respondents were drawn from the Decisions at
      Menopause Study (2002-2003) and from a recent sample of Latin-American immigrants
      to Madrid (2010-2011). The final sample included 484 women after excluding women
      with induced menopause and use of HT. Probit analyses and Cox proportional hazard
      models were used to estimate median age at menopause and to identify factors
      associated with an early age at menopause. RESULTS: Median estimated age at
      natural menopause was 52.0 years (51.2-53.0) for Spanish women and 50.5 years
      (49.9-51.2) for Latin-American women. Immigrant women were more likely to reach
      menopause at an earlier age after controlling for confounding factors.
      Nulliparity and lower levels of education were associated with an earlier age at
      menopause. A higher body mass index was associated with a later age at menopause
      in the Spanish model. Among the Latin-American sample, women from the Dominican
      Republic and women who underwent menopause before migrating were more likely to
      reach menopause at an earlier age. CONCLUSIONS: The results reported here
      demonstrate that early life events, including place of birth, and later life
      events, such as timing of migration, were associated with age at menopause. This
      study highlights the importance of taking into account differences in the age of
      onset of menopause in the multicultural population of Madrid when considering the
      health of women at midlife and beyond.

PMID- 24022911
TI  - Analytic projection from plane-wave and PAW wavefunctions and application to
      chemical-bonding analysis in solids.
AB  - Quantum-chemical computations of solids benefit enormously from numerically
      efficient plane-wave (PW) basis sets, and together with the projector augmented
      wave (PAW) method, the latter have risen to one of the predominant standards in
      computational solid-state sciences. Despite their advantages, plane waves lack
      local information, which makes the interpretation of local densities-of-states
      (DOS) difficult and precludes the direct use of atom-resolved chemical bonding
      indicators such as the crystal orbital overlap population (COOP) and the crystal
      orbital Hamilton population (COHP) techniques. Recently, a number of methods have
      been proposed to overcome this fundamental issue, built around the concept of
      basis-set projection onto a local auxiliary basis. In this work, we propose a
      novel computational technique toward this goal by transferring the PW/PAW
      wavefunctions to a properly chosen local basis using analytically derived
      expressions. In particular, we describe a general approach to project both PW and
      PAW eigenstates onto given custom orbitals, which we then exemplify at the hand
      of contracted multiple-zeta Slater-type orbitals. The validity of the method
      presented here is illustrated by applications to chemical textbook examples
      diamond, gallium arsenide, the transition-metal titanium-as well as nanoscale
      allotropes of carbon: a nanotube and the C60 fullerene. Remarkably, the
      analytical approach not only recovers the total and projected electronic DOS with
      a high degree of confidence, but it also yields a realistic chemical-bonding
      picture in the framework of the projected COHP method.

PMID- 24022912
TI  - Neonatal injury rapidly alters markers of pain and stress in rat pups.
AB  - Less than 60% of infants undergoing invasive procedures in the neonatal intensive
      care unit receive analgesic therapy. These infants show long-term decreases in
      pain sensitivity and cortisol reactivity. In rats, we have previously shown that
      inflammatory pain experienced on the day of birth significantly decreases adult
      somatosensory thresholds and responses to anxiety- and stress-provoking stimuli.
      These long-term changes in pain and stress responsiveness are accompanied by two
      fold increases in central met-enkephalin and beta-endorphin expression. However,
      the time course over which these changes in central opioid peptide expression
      occur, relative to the time of injury, are not known. The present studies were
      conducted to determine whether the observed changes in adult opioid peptide
      expression were present within the first postnatal week following injury. The
      impact of neonatal inflammation on plasma corticosterone, a marker for stress
      reactivity, was also determined. Brain, spinal cord, and trunk blood were
      harvested at 24 h, 48 h, and 7 d following intraplantar administration of the
      inflammatory agent carrageenan on the day of birth. Radioimmunoassay was used to
      determine plasma corticosterone and met-enkephalin and beta-endorphin levels
      within the forebrain, cortex, midbrain, and spinal cord. Within 24 h of injury,
      met-enkephalin levels were significantly increased in the midbrain, but decreased
      in the spinal cord and cortex; forebrain beta-endorphin levels were significantly
      increased as a result of early life pain. Corticosterone levels were also
      significantly increased. At 7 d post-injury, opioid peptides remained elevated
      relative to controls, suggesting a time point by which injury-induced changes
      become programmed and permanent.

PMID- 24022913
TI  - Carbon emissions performance of commercial logging in East Kalimantan, Indonesia.
AB  - Adoption of reduced-impact logging (RIL) methods could reduce CO2 emissions by 30
      50% across at least 20% of remaining tropical forests. We developed two cost
      effective and robust indices for comparing the climate benefits (reduced CO2
      emissions) due to RIL. The indices correct for variability in the volume of
      commercial timber among concessions. We determined that a correction for
      variability in terrain slope was not needed. We found that concessions certified
      by the Forest Stewardship Council (FSC, N = 3), when compared with noncertified
      concessions (N = 6), did not have lower overall CO2 emissions from logging
      activity (felling, skidding, and hauling). On the other hand, FSC certified
      concessions did have lower emissions from one type of logging impact (skidding),
      and we found evidence of a range of improved practices using other field metrics.
      One explanation of these results may be that FSC criteria and indicators, and
      associated RIL practices, were not designed to achieve overall emissions
      reductions. Also, commonly used field metrics are not reliable proxies for
      overall logging emissions performance. Furthermore, the simple distinction
      between certified and noncertified concessions does not fully represent the
      complex history of investments in improved logging practices. To clarify the
      relationship between RIL and emissions reductions, we propose the more explicit
      term 'RIL-C' to refer to the subset of RIL practices that can be defined by
      quantified thresholds and that result in measurable emissions reductions. If
      tropical forest certification is to be linked with CO2 emissions reductions,
      certification standards need to explicitly require RIL-C practices. 

PMID- 24022914
TI  - Reply: To PMID 23097303.

PMID- 24022916
TI  - Formation of hollow iron oxide tetrapods via a shape-preserving nanoscale
      Kirkendall effect.
AB  - Hollow iron oxide tetrapods are synthesized by exposing iron precursors to hollow
      ultrathin PtS tetrapods. Surprisingly, the heterogeneous nucleation and growth of
      iron takes place exclusively within the PtS interior. Oxidation of the resulting
      iron tetrapod produces a hollow iron oxide shell via a shape-preserving
      Kirkendall effect which preserves the morphology of the original tetrapod with
      remarkably high precision, offering a robust synthetic route to hollow iron oxide
      nanostructures of unprecedented geometry. 

PMID- 24022915
TI  - Mesenchymal stromal cells: inhibiting PDGF receptors or depleting fibronectin
      induces mesodermal progenitors with endothelial potential.
AB  - Realizing the full therapeutic potential of mesenchymal stromal/stem cells (MSCs)
      awaits improved understanding of mechanisms controlling their fate. Using MSCs
      cultured as spheroids to recapitulate a three-dimensional cellular environment,
      we show that perturbing the mesenchymal regulators, platelet-derived growth
      factor (PDGF) receptors or fibronectin, reverts MSCs toward mesodermal
      progenitors with endothelial potential that can potently induce
      neovascularization in vivo. MSCs within untreated spheroids retain their
      mesenchymal spindle shape with abundant smooth muscle alpha-actin filaments and
      fibronectin-rich matrix. Inhibiting PDGF receptors or depleting fibronectin
      induces rounding and depletes smooth muscle alpha-actin expression; these cells
      have characteristics of mesenchymoangioblasts, with enhanced expression of
      mesendoderm and endoderm transcription factors, prominent upregulation of E
      cadherin, and Janus kinase signaling-dependent expression of Oct4A and Nanog.
      PDGF receptor-inhibited spheroids also upregulate endothelial markers platelet
      endothelial cell adhesion molecule 1 and vascular endothelial-cadherin and
      secrete many angiogenic factors, and in vivo they potently stimulate
      neovascularization, and their MSCs integrate within functional blood vessels that
      are perfused by the circulation. Thus, MSC potency and vascular induction are
      regulated by perturbing mesenchymal fate.

PMID- 24022918
TI  - The value of cadaver CT scans in gross anatomy laboratory.

PMID- 24022917
TI  - Adipose tissue: another target organ for lead accumulation? A study on Sardinian
      children (Italy).
AB  - OBJECTIVES: This study analyzes the relationship between lead levels and adipose
      tissue in Sardinian children. As an environmental pollutant, lead occurs in two
      different chemical forms: inorganic and organic lead; organic lead is present in
      the environment mainly as lead-alkyls (tetramethyl and tetraethyl lead). The lead
      alkyls are characterized by their liposolubility; because of this characteristic,
      the behavior of organic Pb in the organism is similar to that of persistent
      organic pollutants (POPs). In fact, the high liposolubility of POPs, synthetic
      chemical substances highly resistant to biodegradation in both the environment
      and the human body, gives them a preferential tendency to accumulate in adipose
      tissue. METHODS: The study sample consisted of 759 children between 11 and 15
      years resident in various municipalities of Sardinia. Hair lead levels (PbH) were
      used as the biomarker of exposure, while several anthropometric indexes were
      adopted to evaluate the adipose tissue: weight, body mass index, waist
      circumference, waist to hip circumference ratio, and sum of skinfolds (Sigmaskf).
      RESULTS: The results of the multivariate ridge regression analysis, controlling
      for sex and age, show a significant positive relationship between logPbH and
      logSigmaskf but not the other adiposity indicators. CONCLUSIONS: This results
      suggests that organic lead tends to accumulate in adipose tissue, although it
      would be appropriate to measure lead levels in the adipose tissue itself in order
      to verify the results. Hence this tissue could be considered a possible new
      biological matrix for the evaluation of environmental lead exposure.

PMID- 24022919
TI  - Aquatic exercise is as effective as dry land training to blood pressure reduction
      in postmenopausal hypertensive women.
AB  - BACKGROUND AND PURPOSE: The evidence of the benefits from regular physical
      activity to hypertensives is based on dry land training studies. Therefore, the
      aim of this study is to compare the effect of aquatic exercise with dry land
      training on hypertensive women. METHODS: This is a randomized controlled study
      with 52 post-menopausal hypertensive women. The patients were randomly allocated
      in three groups: water aerobic training group (n = 19), dry land aerobic training
      group (n = 19) and a non-intervention control group (n = 14). The training
      protocol was performed by 12 weeks. RESULTS: There were no differences among the
      three groups concerning basal blood pressure (BP) and biochemical variables. In
      water group, there was a statistically significant reduction of systolic BP from
      136 +/- 16 mm Hg at zero week to 124 +/- 18 mm Hg at 11th week and 124 +/- 15 mm
      Hg at 12th week. In dry land training group, there was a statistically
      significant reduction of systolic BP from 138 +/- 15 mm Hg at zero week to 125 +/
      10 mm Hg at 7th week, 127 +/- 10 mm Hg at 10th week and 126 +/- 9 mm Hg at 12th
      week. The control group presented no change in any of the assessed variables. No
      changes were carried out in any antihypertensive medications during study.
      DISCUSSION: This is a randomized controlled study that demonstrates the
      antihypertensive efficacy of aerobic aquatic exercise.

PMID- 24022920
TI  - A case of progressive quadriceps weakness and elevated creatine kinase level
      mimicking inclusion body myositis.

PMID- 24022921
TI  - Progressive macromolecular self-assembly: from biomimetic chemistry to bio
      inspired materials.
AB  - Macromolecular self-assembly (MSA) has been an active and fruitful research field
      since the 1980s, especially in this new century, which is promoted by the
      remarkable developments in controlled radical polymerization in polymer
      chemistry, etc. and driven by the demands in bio-related investigations and
      applications. In this review, we try to summarize the trends and recent progress
      in MSA in relation to biomimetic chemistry and bio-inspired materials. Our paper
      covers representative achievements in the fabrication of artificial building
      blocks for life, cell-inspired biomimetic materials, and macromolecular
      assemblies mimicking the functions of natural materials and their applications.
      It is true that the current status of the deliberately designed and obtained nano
      objects based on MSA including a variety of micelles, multicompartment vesicles,
      and some hybrid and complex nano-objects is at their very first stage to mimic
      nature, but significant and encouraging progress has been made in achieving a
      certain similarity in morphologies or properties to that of natural ones. Such
      achievements also demonstrate that MSA has played an important and irreplaceable
      role in the grand and long-standing research of biomimetic and bio-inspired
      materials, the future success of which depends on mutual and persistent efforts
      in polymer science, material science, supramolecular chemistry, and biology. 

PMID- 24022923
TI  - [Research on pediatric endocrine and inherited metabolic disorders in China].

PMID- 24022924
TI  - [Comparison of clinical application of two definitions of metabolic syndrome in
      children and adolescents].
AB  - OBJECTIVE: To compare and evaluate clinical applications of two definitions of
      metabolic syndrome in children and adolescents, which was developed by Pediatric
      Academy of Chinese Medical Association in 2012 (Chinese definition) and by
      International Diabetes Federation in 2007 (IDF definition), respectively.
      METHODS: 593 obese children and adolescents aged 10 ?16 y from July 2006 to
      December 2012 were enrolled in the study. The diagnostic concordance of two
      definitions for metabolic syndrome and individual components was estimated, and
      their sensitivity and specificity for detecting insulin resistance and early
      macrovascular complications were compared. RESULTS: The concordance between two
      definitions for diagnosing metabolic syndrome was good (kappa=0.626); as for
      detecting the individual components, the Kappa concordance index were 1.000,
      0.803, 0.780, 0.734 and 0.594 for hypertriglyceridemia, hyperglycemia,
      cholesterol abnormality and hypertension, respectively. The incidence of insulin
      resistance and early macrovascular complications, detected by the two
      definitions, were both increased with increasing number of abnormal components.
      The sensitivity and specificity for detecting insulin resistance in children with
      metabolic syndrome were 54.5% and 65.7% by Chinese definition, and 36.1% and
      83.1% by IDF definition; while the sensitivity and specificity for detecting
      early macrovascular complications were 58.3% and 55.8% by Chinese definition, and
      37.3% and 70.8% by IDF definition. After adjusting for age and sex, compared to
      the obese children and adolescents without metabolic syndrome, the odds ratios of
      insulin resistance and early macrovascular complications were 2.166 (P<0.001) and
      1.771(P=0.008) for children with metabolic syndrome diagnosed by Chinese
      definition, and the odds ratio of insulin resistance and early macrovascular
      complications were 2.618 (P<0.001) and 1.357 (P=0.190) by IDF definition.
      CONCLUSION: The concordance between Chinese and IDF definitions for diagnosing
      metabolic syndrome in Chinese obese children and adolescents is good. Compared to
      IDF definition, Chinese definition is more sensitive for hypertension,
      hyperglycemia and hypercholesterolemia, thus it can more effectively detect
      insulin resistance and early macrovascular complication.

PMID- 24022922
TI  - alpha6-Integrin is required for the adhesion and vasculogenic potential of
      hemangioma stem cells.
AB  - Infantile hemangioma (IH) is the most common tumor of infancy. Hemangioma stem
      cells (HemSC) are a mesenchymal subpopulation isolated from IH CD133+ cells.
      HemSC can differentiate into endothelial and pericyte/smooth muscle cells and
      form vascular networks when injected in immune-deficient mice. alpha6-Integrin
      subunit has been implicated in the tumorgenicity of glioblastoma stem cells and
      the homing properties of hematopoietic, endothelial, and mesenchymal progenitor
      cells. Therefore, we investigated the possible function(s) of alpha6-integrin in
      HemSC. We documented alpha6-integrin expression in IH tumor specimens and HemSC
      by RT-qPCR and flow cytometry. We examined the effect of blocking or silencing
      alpha6-integrin on the adhesive and proliferative properties of HemSC in vitro
      and the vasculogenic and homing properties of HemSC in vivo. Targeting alpha6
      integrin in cultured HemSC inhibited adhesion to laminin but had no effect on
      proliferation. Vessel-forming ability in Matrigel implants and hepatic homing
      after i.v. delivery were significantly decreased in alpha6-integrin siRNA
      transfected HemSC. In conclusion, alpha6-integrin is required for HemSC adherence
      to laminin, vessel formation in vivo, and for homing to the liver. Thus, we
      uncovered an important role for alpha6 integrin in the vasculogenic properties of
      HemSC. Our results suggest that alpha6-integrin expression on HemSC could be a
      new target for antihemangioma therapy.

PMID- 24022925
TI  - [Early identification of impaired renal function in obese children with non
      alcoholic fatty liver disease].
AB  - OBJECTIVE: To early assess the impaired renal function in the obese children with
      non-alcoholic fatty liver disease (NAFLD) and to identify the relationship
      between NAFLD and impairment of renal function. METHODS: Three hundred and eighty
      six obese children were enrolled and divided into NAFLD group and simple obesity
      group (control) according to the diagnostic criteria. Clinical biochemical
      parameters and early impaired renal functions were evaluated and compared. Among
      all patients 234 obese children aged over 10 y were subdivided into 3 groups:
      NAFLD combined with metabolic syndrome (NAFLD+MS) group, NAFLD group and simple
      obesity group (control), and the above indexes were compared among 3 groups.
      RESULTS: The urinary microalbumin levels in NAFLD, NAFLD+MS (>10y) and NAFLD
      groups (>10y) were significantly higher than those in controls. Additionally, the
      positive correlations of urinary microalbumin with systolic pressure,
      triglyceride and 2h-postprandial blood glucose were found. CONCLUSION: There is
      early renal dysfunction in children with NAFLD and those accompanied with MS,
      which may be associated with hypertension and glucose-lipid metabolic disorder.
      The results indicate that NAFLD is not only an early sign of early impaired renal
      function but also an early stage of chronic kidney disease (CKD) in obese
      children.

PMID- 24022926
TI  - [Survey on quality of life in children and adolescents with type 1 diabetes].
AB  - OBJECTIVE: To survey the quality of life in children and adolescents with type 1
      diabetes. METHODS: Ninety-eight children and adolescents with type 1 diabetes who
      participated in Diabetes Summer Camp held in Chongqing, Wuhan and Cheng during
      2012 April and December were recruited in the study. The American juvenile
      diabetes patients quality of life scale Diabetes Quality of Life for Youths was
      used to assess the quality of life and SPSS19.0 was used for statistical
      analysis. RESULTS: The scale had satisfactory reliability and validity with a
      Cronbach's Alpha score of 0.942 and a validity score of 0.679. All three
      dimension of scales: scales of impact, scales of worries and scales of
      satisfaction were significantly correlated with self-health assessment (P<0.01).
      The scores of impact and worries accounted for >50% of total scores as the same
      for the self health assessment scores. The score of disease course, diet and
      blood glucose control were positive correlated with each other. Age and HbA1c
      were positively correlated with the scale of impact, while gender has negative
      correlation with satisfaction scale (P<0.05). The diabetes diet had significant
      effects on the quality of life. CONCLUSION: The quality of life in children and
      adolescents with type 1 diabetes is decreased, especially for those with longer
      disease course and female adolescents. The form of Diabetes Quality of Life for
      Youth used in the study has good reliability and validity, which can reflect the
      quality of life of Chinese diabetic children and adolescents.

PMID- 24022927
TI  - [Epidemiologic study on current pubertal development in Chinese school-aged
      children].
AB  - OBJECTIVE: To survey the current status of pubertal development of Chinese
      children and to compare the precocious puberty prevalence of different regions.
      METHODS: A cross-sectional epidemiological study was conducted on 18 707 children
      and adolescents aged 6?18 y with male/female ratio of 9 812/8 895 from 6
      representative geographical areas in China, including Beijing, Tianjin, Hangzhou,
      Shanghai, Chongqing and Nanning. The height, weight, waist circumference (WC),
      hip circumference(HC) and sexual maturation states (Tanner stages: breast stages
      for girls and testicular volume for boys) of children and adolescents were
      measured. Probit analysis was used to calculate the median age and 95% confidence
      interval (CI) for onset of breast and testicular development. The prevalence of
      precocious puberty of different regions and BMI, waist circumference of different
      groups were compared. RESULTS: Breast development before 8 y was observed in
      2.91% of girls, and testicular volume 4 ml or more before 9 y was observed in
      1.74% of boys. The median age of onset of Tanner stages 2 for breast development
      in girls was 9.69 y (95% CI: 9.63? 9.75); the median age of onset of puberty as
      indicated by Tanner stages 2 for testicular development in boys was 11.25 y
      (95%CI:11.19? 11.30). The prevalence of precocious puberty (43 girls and 37 boys)
      was 0.43% (80/18 707). The prevalence of precocious puberty in northern region
      was higher than that in southwest region (0.736% compared with 0.282% P<0.05).
      There was no difference in onset age of precocious puberty in girls among three
      regions; but the onset age of precocious puberty in boys was earlier in east
      China [(7.4+/-0.28)y]. The SD values of BMI and waist-to-hip ratio (W/H) in
      precocious puberty children were higher than those in the peer normal children.
      There was no difference in BMI,waist circumference and waist-to-hip ratio in the
      precocious puberty children among different regions. CONCLUSION: The current
      diagnostic criteria of precocious puberty are suitable for the children in the
      survey areas. The prevalence and the onset age of precocious puberty are various
      in different regions. A positive association between obesity and precocious
      puberty is found both in boys and girls.

PMID- 24022928
TI  - [HEXB gene study and prenatal diagnosis for a family affected by infantile
      Sandhoff disease].
AB  - OBJECTIVE: To investigate the phenotype and genotype of a Chinese boy and his
      family affected by infantile Sandhoff disease. METHODS: The proband, a boy, was
      the first child born to a non-consanguineous couple. He showed startle reaction
      after birth and progressive psychomotor regression from the age of 8 months. From
      the age of 16 months, he presented seizures. When he was admitted at 17 months
      old, severe mental retardation and weakness were observed. Fundus examination
      revealed bilateral cherry-red spots in the macula and optic atrophy. Cranial MRI
      revealed abnormal signals in the thalamus, basal ganglia and white matter.
      Enzymatic assay and genetic testing were performed for the diagnosis. His mother
      visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene
      diagnosis to the fetus was performed by direct sequencing. RESULTS: Significant
      deficient total beta-hexosaminidase (A and B) activity in peripheral leucocytes
      of the patient (0.0 nmol/h/mg compared with normal control, 41.9 to 135.1
      nmol/h/mg) supported the diagnosis of Sandhoff disease. On his HEXB gene, two
      mutations were found. c.1645G-A (p.G549R) was novel. c.IVS7-48T was a reported
      mutation. Now, the patient was 2 years and 3 months old, with progressive general
      failure, severe epilepsy, blindness and hypermyotonia. Subsequently, the mother
      visited us at 18 weeks of pregnancy seeking for prenatal diagnosis. HEXB gene
      analysis of the amniocytes was performed by direct sequencing. Both of the two
      mutations were not detected from cultured amniocytes. The result revealed that
      the fetus was not affected by Sandhoff disease. A healthy girl, the sibling of
      the proband, was born in term. Postnatal enzyme analysis and genetic analysis of
      the cord blood cells confirmed the prenatal diagnosis. CONCLUSION: One novel
      mutation on HEXB gene was identified. Prenatal diagnosis to the fetus of this
      family was performed by amniocytes gene analysis.

PMID- 24022929
TI  - [Hand and wrist bone maturation in children with central precocious puberty and
      idiopathic short stature].
AB  - OBJECTIVE: To investigate the maturation of individual bones on the hand and
      wrist in children with central precocious puberty (CPP) and idiopathic short
      stature (ISS). METHODS: Hand and wrist films of 25 children with CPP, 29 children
      with ISS and 21 normal controls were evaluated by conventional Greulich-Pyle (GP)
      atlas method and individual bone assessment method, in which all twenty bones of
      the hand and wrist were evaluated based on GP atlas, including 2 radius and ulna,
      7 carpal bones, 11 metacarpal and phalangeal bones, the average bone age (BA) was
      calculated. The differences in groups were analyzed by independent samples t
      test. The differences between the two methods were analyzed by paired sample t
      test. The differences between BA and chronological age (CA) were analyzed by ROC
      with SPSS 17.0. RESULTS: Compared with the normal control group, the advance of
      BA in the CPP group was 0.70-2.26 y (1.48 +/-0.78) by the GP atlas method, while
      that was 0.28-2.00 y(1.14 +/-0.86) by the individual bone evaluation method. In
      all twenty bones, the advance of metacarpal and phalangeal BA was the greatest
      [0.34-2.06 y(1.2+/-0.86)]. In the ISS group,the delay of BA was 0.47-2.91 y(
      1.69+/-1.22) by the GP atlas method, while that was 0.48-2.50 y (-1.49+/-1.01) by
      individual bone evaluation method.The delay of carpal BA was the greatest [0.59
      2.73 y(-1.66+/-1.07)] in all twenty bones. In the ISS group and the normal
      control group, there were no statistic differences between the two methods. In
      the CPP group, statistic difference was found between two methods. There were no
      statistic differences for the areas under ROC curves between two methods.
      CONCLUSION: The advance of metacarpal and phalangeal BA is the greatest in CPP
      group and the delay of carpal BA is the greatest in ISS group.Both methods
      provide diagnostic information for bone age in CPP and ISS children.

PMID- 24022931
TI  - [Detection of somatic mutations in deteriorated cell of peritoneal mesothelioma
      by whole genome sequencing].
AB  - OBJECTIVE: To detect the somatic mutations in peritoneal mesothelioma with whole
      genome sequencing technique. METHODS: Surgically resected cancer and
      pericancerous tissue samples from one patient with peritoneal mesothelioma were
      obtained. The whole genome sequences of tumor tissue and pericancerous tissue
      were examined by the second generation sequencing technique and compared with
      reference sequences from human genome database. RESULTS: There were 639 717
      single nucleotide variations (Single Nucleotide Variation SNV) found in both
      tumor and pericancerous tissue cells; while 20 302 SNVs were unique for tumor
      cells and 2 185 SNVs unique for pericancerous tissue, but still 223 SNVs found in
      cancer and pericancerous tissue were differed from those in human genome
      database. CONCLUSION: The preliminary results indicate that merely comparing the
      gene sequences of cancer and pericancerous tissue samples in an individual with
      the human genome reference sequence can not accurately locate all somatic
      mutations in pathological cells. For those individualized diseases caused by
      random somatic mutations, it is suggested to sequence the whole genome at birth
      or at least to reserve a DNA sample at early age for both research and clinical
      needs.

PMID- 24022930
TI  - [Effect of Xinfeng Capsule on lung function in rats with adjuvant-induced
      arthritis and its mechanism].
AB  - OBJECTIVE: To investigate the effects of Xinfeng Capsule (XFC) on pulmonary
      function and related mechanism in adjuvant-induced arthritis (AA) rats. METHODS:
      The rats were randomly divided into five groups: normal control (NC), model
      control (MC) groups, methotrexate (MTX), tripterygium glycosides tablet (TPT) and
      Xinfeng capsule (XFC) treatment groups. The adjuvant-induced arthritis model was
      established by intracutaneous injection of 0.1 mL Freund ' s complete adjuvant in
      the right paw of rats; the drugs were given 19 d after model establishment. The
      toe swelling degree (E), arthritis index (AI), pulmonary function, peripheral
      blood Treg levels, pathological changes of lung tissue and expression of Foxp3,
      TGF-beta1, Smad3, Smad7 proteins in lung tissue were measured 30 d after drug
      administration. RESULTS: Compared to NC group, the levels of E, AI, alveolitis
      score, TGF-beta1 and Smad3 were significantly increased (P <0.05 or P <0.01);
      maximum expiratory flow 25% of vital capacity (FEF25),50% maximal expiratory
      vital capacity flow (FEF50), maximum expiratory flow at 75% of vital capacity
      (FEF75), maximum mid-expiratory flow (MMF), force peak expiratory flow (PEF),
      CD4+ CD25+ Treg, Foxp3 and Smad7 were significantly decreased in MC group (P
      <0.05 or P < 0.01). Compared to MC group,the expression of E, AI, TGF-beta1 and
      Smad3 were reduced, while FEF50, FEF75, MMF, PEF, Treg, Foxp3 and Smad7 were
      elevated in XFC group (P <0.05 or P <0.01). Compared to XFC group, the level of
      body mass,FEF25,FEF50, FEF75, MMF and Treg were lower in MTX and TPT groups (P
      <0.05 or P <0.01). CONCLUSION: There are inflamed joints and reduced pulmonary
      function in rats of adjuvant-induced arthritis. XFC can inhibit paw edema
      degrees, reduce arthritis response, and improve pulmonary function, which is
      associated with up-regulating expression of Treg and Foxp3, down-regulating the
      expression of TGF-beta1 and adjusting TGF-beta1/Smads signal pathway.

PMID- 24022932
TI  - [Harringtonine induces apoptosis in NB4 cells through down-regulation of Mcl-1].
AB  - OBJECTIVE: To investigate the growth inhibition effect, cytotoxicity and
      apoptotic induction of harringtonine (HT) in human acute promyelocytic leukemia
      (APL) NB4 cells,and the related mechanism. METHODS: NB4 cells were treated with
      HT. Total cell numbers were counted by hemocytometer, and cell viabilities were
      determined by trypan blue exclusion. Apoptotic cells were determined by
      fluorescence microscopy and FACS after staining with AO and EB or PI,
      respectively. The cleavage of PARP and the activation of Bax and the expression
      of anti-apoptotic proteins were determined by Western Blot. siRNA was used to
      silence the expression of target genes. Primary cells were isolated following
      Ficoll-Hypaque density gradient centrifugation method. RESULTS: HT inhibited cell
      growth and induced apoptosis of NB4 cells in a dose- and time-dependent manner.
      Apoptosis induced by HT was correlated with the down-regulation of Mcl-1 and the
      cleavage of PARP, while HT did not affect the protein level of Bax and Bak or
      change the protein level of Bcl-2. The silence of Bcl-XL sensitized HT-induced
      apoptosis in NB4 cells.Apoptosis induced by HT in primarily cultured APL cells
      was also correlated with the down-regulation of Mcl-1. CONCLUSION: HT inhibits
      cell growth and induces apoptosis in NB4 cells and primarily cultured APL cells,
      which may be associated with down-regulation of Mcl-1.

PMID- 24022933
TI  - [Effect of Oxaliplatin on cell cycle of hepatocellular carcinoma cell line
      HepG2].
AB  - OBJECTIVE: To investigate the effect of Oxaliplatin (L-OHP) on cell cycle in
      hepatocellular carcinoma cell line HepG2 and the involved mechanism. METHODS:
      Inhibitory effect of L-OHP on the proliferation of HepG2 cells was determined by
      MTT assay. Cell cycle distribution was shown by flow FCM. The expression levels
      of cyclinD1, CDK2, CDK4, p16, p21, p53 were detected by RT-PCR and Western blot.
      RESULTS: MTT method revealed that L-OHP inhibited proliferation of hepatocellular
      carcinoma HepG2 cells in a dose- and time-dependent manner. L-OHP induced S cell
      cycle arrest in HepG2 cell; down-regulated the levels of CDK4, cyclinD1 and up
      regulated the levels of p21, p53. There were no significant changes of CDK2 and
      p16 after L-OHP treatment. CONCLUSION: L-OHP inhibits the proliferation of HepG2
      cells by blocking cell at S stage, which may be resulted from the activity of
      CDK4, CyclinD1 and p21.

PMID- 24022934
TI  - [Expression of EZH2 in breast cancer and its clinicopathological significance].
AB  - OBJECTIVE: To investigate the expression of EZH2 in breast cancer and its
      clinicopathological significance. METHODS: Eighty cases of invasive breast cancer
      with complete clinlcpathological data and follow-up information were enrolled in
      the study. The expressions of ER, PR, HER-2, CK5/6, CK14, EGFR and EZH2 proteins
      were detected by immunohistochemistry (IHC). The relationship of EZH2 expression
      with molecular subtypes and prognosis of breast cancer was analyzed. RESULTS: In
      80 cases of breast cancer, there were 49 cases of Luminal subtype, 8 cases of HER
      2(+) subtype, 20 cases of Basal-like subtype and 3 cases of Normal breast-like
      subtype. The molecular subtypes of breast cancer were associated with menopausal
      status of patients. Luminal subtype had the highest overall survival rate, while
      the Basal-like carcinomas were associated with the lowest survival (P< 0.05). The
      overall EZH2-positive expression rate was 45.00% and the expression was
      correlated with axillary lymph node metastasis, histological grading and clinical
      staging of breast cancer (P < 0.05). The EZH2-positive expression rates in
      Luminal subtype, HER-2(+) subtype and Basal-like subtype of breast cancers were
      34.6%,50.0% and 70.0%, respectively (P <0.05). CONCLUSION: Positive expression of
      EZH2 may indicate a poor prognosis of breast cancer patients and it might be used
      as a novel therapeutic target for breast cancer of Basal-like subtype.

PMID- 24022935
TI  - [Correlation of neurochemical metabolism with memory function in young adult
      patients with first-episode depression studied with proton magnetic resonance
      spectroscopy].
AB  - OBJECTIVE: To investigate the correlation of neurochemical metabolism in
      hippocampus with memory function in young adult patients with first-episode
      depression. METHODS: Twenty patients with first-episode depression (patient
      group) and fifteen health subjects (control group) were enrolled in the study.
      The neurochemical metabolism, including the levels of N-acetylaspartate (NAA),
      Choline (Cho), Creatine (Cr), Myoinositol (mI) were measured by proton magnetic
      resonance spectroscope (1H-MRS) in bilateral hippocampus. Wechsler Memory Scale
      (WMS) were used to examine the memory function in both groups. RESULTS: The
      memory quotient (89.15 +/-6.62) of patient group was significantly lower than
      that of controls (P <0.01),the scores of long-term memory,short-term memory and
      immediate memory in patients were also lower than those of controls (P<0.05 or
      0.01). In patient group, the ratio of NAA/Cr (1.34 +/-0.08) in the left
      hippocampus was significantly lower than that of control group (P<0.01); and the
      ratio of mI/Cr in the bilateral hippocampus [(0.63 +/-0.13) in left and (0.6 +/
      0.1) in right] was significantly higher than those in control group (P<0.05). In
      patient group,the ratio of NAA/Cr in the left hippocampus was positively
      correlated with WMS scores (P<0.01), and the ratio of mI/Cr in the left
      hippocampus was negatively correlated with WMS scores (P<0.05). CONCLUSION: The
      memory deficit and abnormal metabolism function of neuron cell in hippocampus
      coexist in young adult patients with first-episode depression, and the lower
      NAA/Cr and higher mI/Cr ratio in the left hippocampus may result in the memory
      deficit.

PMID- 24022936
TI  - [Retrospective analysis of 202 pathological autopsy cases in medical dispute].
AB  - OBJECTIVE: To analyze the characteristics of autopsies in medical dispute.
      METHODS: The data of 202 autopsy cases in medical disputes performed by the
      Department of Pathology of Jiangxi Medical College from January 2001 to December
      2010 were retrospectively analyzed. RESULTS: The number of autopsy in medical
      disputes increased year by year. Neonatal, infant and 30 ? 60y were more common
      age groups in dispute; the gender ratio of male to female was 2:1 and more cases
      were from hospitals in rural areas. Most medical disputes came from in
      departments of pediatric, obstetrics and gynecology and general surgery. Death
      caused by cardiovascular diseases ranked at the first place. CONCLUSION: Autopsy
      is important in medical disputes to define the cause of death and to preserve
      evidence.

PMID- 24022937
TI  - [Research advances on the role of mast cells in pelvic pain of endometriosis].
AB  - Endometriosis (EMs) is a common gynecologic disease that affects women's physical
      and mental health seriously. The pathogenesis is still unknown and the mechanism
      of endometriosis-associated pain remains unclear. Mast cells (MC) are known to be
      multifunctional players in the immune system. Recent studies have shown that
      nerve fibers in EMs lesions can release neural peptides such as nerve growth
      factor and substance P to induce MC degranulating and releasing histamine,
      proteases, cytokines, chemokines etc., which contributes to the development of
      pain and hyperalgesia in patients with endometriosis. 

PMID- 24022938
TI  - [Research progress in pathogenicity of Ureaplasma urealyticum].
AB  - Ureaplasma urealyticum (UU) is closely related to human diseases including non
      gonococcal urethritis (NGU), infertility, premature membranes and neonatal
      bronchopulmonary dysplasia. Researches on the pathogenicity of UU have become a
      hot topic in recent years, and suggest that many potential pathogenicity genes or
      putative pathogenicity islands are involved in its virulence. Moreover, the
      biovar and serum types of UU, the infection concentration and the state of the
      host immune system are also important to determine whether UU can cause human
      disease or not. In this article the recent progress of researches in the
      pathogenicity of UU is reviewed. 

PMID- 24022939
TI  - [From endoplasmic reticulum to Golgi apparatus: a secretory pathway controlled by
      signal molecules].
AB  - Protein transport from endoplasmic reticulum (ER) to Golgi apparatus has long
      been known to be a central process for protein quality control and sorting.
      Recent studies have revealed that a large number of signal molecules are involved
      in regulation of membrane trafficking through ER, ER-Golgi intermediate
      compartment and Golgi apparatus. These molecules can significantly change the
      transport rate of proteins by regulating vesicle budding and fusion. Protein
      transport from ER to Golgi apparatus is not only controlled by signal pathways
      triggered from outside the cell, it is also regulated by feedback signals from
      the transport pathway. 

PMID- 24022940
TI  - Effects of gold and silver nanoparticles in cultured human osteoarthritic
      chondrocytes.
AB  - The aim of our study was to evaluate the effects of gold (Au) and silver (Ag)
      nanoparticles (NPs) at different concentrations on cultured human osteoarthritic
      chondrocytes. Cell viability and inducible nitric oxide synthase expression were
      evaluated by light microscopy. Using transmission electron microscopy (TEM) and
      field emission gun-based scanning transmission electron microscopy/energy
      dispersive spectroscopy (FEG-STEM/EDS) allowed us to localize NPs. Gene
      expression of matrix metalloproteinases 1, 3 and 13 and A disintegrin and
      metalloproteinase with thrombospondin motifs -4 and -5 were carried out by real
      time polymerase chain reaction. A cell viability test indicated a significant
      dose-dependent cytotoxic effect of both NPs. At concentrations of 160 and 250 MUM
      NP light microscopy showed chondrocytes with signs of apoptosis and an increased
      presence of inducible nitric oxide synthase. Au-NPs were characterized by FEG
      STEM/EDS and TEM analysis localized NPs in cytoplasm and in endocytotic vesicles.
      On the contrary, the Ag-NPs were undetectable by FEG-STEM/EDS and TEM. Increased
      gene expression, particularly in matrix metalloproteinase-3, was observed for
      both NPs (160 MUM), but at a concentration of 250 MUM the expression of the
      evaluated genes became lower. Our in vitro studies, although preliminary, suggest
      that engineered Au and Ag-NPs appear to be harmful for human osteoarthritic
      chondrocytes in high concentrations (160-250 MUM).

PMID- 24022941
TI  - Physician opinions about an anatomy core curriculum: a case for medical imaging
      and vertical integration.
AB  - Pre-clinical anatomy curricula must provide medical students with the knowledge
      needed in a variety of medical and surgical specialties. But do physicians within
      specialties agree about what anatomical knowledge is most important in their
      practices? And, what is the common core of anatomical knowledge deemed essential
      by physicians in different specialties? Answers to these questions would be
      useful in designing pre-clinical anatomy courses. The primary aim of this study
      was to assess the importance of a human gross anatomy course by soliciting the
      opinions of physicians from a range of specialties. We surveyed 93 physicians to
      determine the importance of specific anatomical topics in their own practices.
      Their responses were analyzed to assess variation in intra- and inter
      departmental attitudes toward the importance of anatomy. Nearly all of the topics
      taught in the course were deemed important by the clinicians as a group, but
      respondents showed little agreement on the rank order of importance of anatomical
      topics. Overall, only medical imaging received high importance by nearly all
      respondents, and lower importance was attached to embryology and lymphatic
      anatomy. Our survey data, however, also suggested distinct hierarchies in the
      importance assigned to anatomical topics within specialties. Given that
      physicians view the importance of anatomy differently, we suggest that students
      revisit anatomy through a vertically integrated curriculum tailored to provide
      specialty-specific anatomical training to advanced students based on their areas
      of clinical interest. Integration of medical imaging into pre-clinical anatomy
      courses, already underway in many medical schools, is of high clinical relevance.

PMID- 24022942
TI  - Screening symptoms of reactive attachment disorder: evidence for measurement
      invariance and convergent validity.
AB  - The Relationship Problems Questionnaire (RPQ) was developed to screen symptoms of
      the inhibited and disinhibited subtype of reactive attachment disorder (RAD).
      This study further examines the psychometric properties of the RPQ in children
      with severe emotional and behavioural problems by testing its measurement
      invariance across informants and its convergent validity. Parents and teachers of
      152 children [mean age (Mage) = 7.92] from 20 schools for special education
      filled out the RPQ and the Strengths and Difficulties Questionnaire (SDQ). During
      a home visit in a subsample of 77 children the Disturbances of Attachment
      Interview (DAI) was administered to the caregiver and the child was observed
      using an observational schedule for RAD. Exploratory and confirmatory factor
      analyses revealed the expected two-factor structure for both parent and teacher
      RPQ. Configural and metric invariance, but no scalar invariance, were obtained
      across informants. Both RPQ-subscales had acceptable to good internal
      consistencies and correlated as expected with similar DAI-subscales. Furthermore,
      the disinhibited RPQ-scale related with observations of the child's approach to a
      stranger. Finally, significant associations were found between the RPQ and the
      SDQ. Overall, the RPQ has good psychometric qualities as a multi-informant
      instrument for RAD-symptoms in children with severe emotional and behavioural
      problems.

PMID- 24022943
TI  - Attachment in adults with intellectual disabilities: preliminary investigation of
      the psychometric properties of the manchester attachment scale-third party
      observational measure.
AB  - BACKGROUND: The Manchester Attachment Scale-Third party observational measure
      (MAST) was developed to assess secure attachment style for adults with
      intellectual disabilities. The psychometric properties of the MAST were examined.
      MATERIALS AND METHODS: Professional carers (N = 40) completed the MAST and
      measures related to the construct of attachment theory [Edward Zigler-Yale
      Personality Questionnaire (EZPQ), Emotional Rating Scale (ERS) and the Learning
      Disability Casemix Scale (LDCS)] regarding individuals with an intellectual
      disability (N = 57). Individuals with an intellectual disability (N = 14)
      completed the Self-report Assessment of Attachment Security (SRAAS). RESULTS: The
      MAST was found to have good internal consistency, test-retest reliability and
      convergent validity. MAST scores were negatively correlated with level of
      intellectual disability and challenging behaviour (CB) as measured by LDCS.
      CONCLUSIONS: Support was provided for the reliability and validity of the MAST
      and a relationship between attachment security, level of intellectual disability
      and CB. The results of the study and implications of attachment theory for
      service provision are discussed.

PMID- 24022944
TI  - Health-related Internet use by patients with systemic sclerosis and other
      autoimmune diseases: comment on the article by van der Vaart et al.

PMID- 24022946
TI  - The oxide anion accelerated retro-diels-alder reaction.
AB  - The widespread application of the retro-Diels-Alder reaction in synthesis has
      been hampered by the high temperatures usually required to effect cycloreversion.
      The discovery of the anionic oxy-Cope reaction was followed by predictions that
      the accelerating effect of the oxide anion should also be observed with other
      pericyclic reactions. Recently, such predictions have been confirmed for the
      retro-Diels-Alder reaction, which often proceeds rapidly at room temperature by
      oxide anion rate acceleration. Such mild retro-Diels-Alder reactions have now
      been employed in the synthesis of a range of molecular targets, including
      temperature-sensitive enediynes. 

PMID- 24022947
TI  - A Triangular Iron(III) Complex Potentially Relevant to Iron(III)-Binding Sites in
      Ferreascidin.
AB  - An asymmetric triangular Fe(III) complex has been synthesized by an unusual
      Fe(II) -promoted activation of salicylaldoxime. Formation of the ligand 2
      (bis(salicylideneamino)methyl)phenol in situ is believed to occur through the
      reductive deoximation of salicylaldoxime by ferrous ions. The trinuclear ferric
      complex has been characterized on the basis of elemental analysis, IR, variable
      temperature magnetic susceptibility, and EPR and Mossbauer spectroscopies. The
      molecular structure established by X-ray diffraction consists of a trinuclear
      structure with a [Fe3 (MU3 -O)(MU2 -OPh)](6+) core. Two iron ions are in a
      distorted octahedral environment having FeN2 O4 coordination spheres, and the
      five-coordinated third iron ion, with an FeNO4 coordination sphere, is in a
      trigonal bipyramidal environment. The magnetic susceptibility measurements
      revealed an St = 5/2 ground state with the antiparallel exchange interactions J =
      - 34.3 cm(-1) , J' = - 4.7 cm(-1) , and D = - 0.90 cm(-1) . The EPR results are
      consistent with a ground state of S = 5/2 together with a negative D5/2 value.
      The Mossbauer isomer shifts together with the quadrupole splitting also provide
      evidence for the high-spin state of the three ferric sites. Magnetic Mossbauer
      spectra lead to the conclusion that the internal magnetic fields possibly lie in
      the plane of the three ferric ions. 

PMID- 24022948
TI  - Heterosupramolecular Chemistry: Self-Assembly of an Electron Donor (TiO2
      Nanocrystallite)-Acceptor (Viologen) Complex.
AB  - A TiO2 nanocrystallite has been modified to recognise and selectively bind, by
      complementary hydrogen bonding, a uracil substrate incorporating a viologen
      moiety. Band-gap excitation of the self-assembled donor (TiO2 nanocrystallite)
      acceptor (viologen) complex results in electron transfer. Some implications of
      these findings for the self-assembly of functional nanostructures containing both
      condensed phase and molecular components are considered. 

PMID- 24022949
TI  - Hexabromotricyclobutabenzene and hexabromohexaradialene: their nickel-mediated
      one-pot syntheses and crystal structure.
AB  - The reaction of hexakis(dibromomethyl)benzene with [(Bu3 P)2 -Ni(COD)] (COD = 1,5
      cyclooctadiene) in DMF at 65-70 degrees C yielded a mixture of the title
      compounds. The mixture was separated by column chromatography to yield
      hexabromotricyclobutabenzene (3 a) and hexabromohexaradialene (4) in 24 and 16%
      yields, respectively. (1) H and (13) C NMR spectroscopy suggest that 3 is
      obtained as the syn-all-trans isomer 3 a, and the symmetric anti-all-trans isomer
      3 b is not obtained at all. The X-ray structures of 3 a and 4 are reported. The
      hexaradialene 4 has a chair conformation, and deviates from planarity by 43.6
      degrees . Heat or radical impurities cause the clean transformation of 3 a to 4. 

PMID- 24022950
TI  - Theoretical investigation of the mechanism of the baeyer-villiger reaction in
      nonpolar solvents.
AB  - The Baeyer-Villiger reaction of p-anisaldehyde with peroxyacetic acid in nonpolar
      solvents to give p-anisylformate was examined on the basis of ab initio molecular
      orbital calculations. To explain the experimental observations, the free-energy
      change was evaluated for each case in the absence and in the presence of an acid
      catalyst. It was found that, without catalysts, the rate-determining step
      corresponds to the carbonyl addition of peroxyacetic acid to p-anisaldehyde and
      the reaction hardly occurs. Acetic acid was found to catalyze the carbonyl
      addition and change the rate-determining step from the carbonyl addition to the
      migration of the carbonyl-adduct intermediate. Trifluoroacetic acid was observed
      to catalyze both the carbonyl addition and migration, and the carbonyl addition
      was demonstrated to be a rate-determining step. The results provided a convincing
      explanation of the complex kinetics seen experimentally. Further calculations
      were performed for the reaction of benzaldehyde with peroxyacetic acid to give
      phenylformate. Migratory aptitude was found to depend on the catalyst. Isotope
      effects were also investigated, and the exceptional isotope effect observed
      experimentally was shown to be due to the rate-determining carbonyl addition
      caused by autocatalysis. It is concluded that the mechanism of the reaction
      varies with catalysis or substituent effects. 

PMID- 24022951
TI  - Terrylenimides: New NIR Fluorescent Dyes.
AB  - Terrylenimides 3 and 4 represent a new class of blue colorants, exhibiting
      absorption maxima at 650 to 700 nm and fluorescence emissions in the NIR region
      (673 to 750 nm). The terrylenimides were synthesized by means of various
      organometallic coupling reactions, catalyzed by transition metal complexes (Ni(o)
      , Pd(o) ) and starting from the aromatic bromides, boronic acids, or organotin
      compounds. The terrylenimides have all the properties expected of excellent
      fluorescent dyes: high extinction coefficients, high fluorescence quantum yields,
      and very good thermal, chemical, and photochemical stabilities. Owing to its
      extended pi system, 3 can reversibly accept four negative charges. By varying the
      substituents, 3 and 4 can be modified to serve either as soluble dyes or as
      insoluble pigments. 

PMID- 24022952
TI  - Syntheses, Crystal Structures, and Properties of Novel Heterooctametallic
      Clusters Na2 M'2 [M3 O4 (O2 CEt)8 ]2 (M' = Fe, Cr, Mo; M3 = Mo3 , MoW2 , W3 ).
AB  - A mixture of Na2 MO4 , M(CO)6 , FeCl3 .6H2 O, and (EtCO)2 O was heated at 120
      degrees C to produce the heterooctanuclear clusters Na2 Fe2 [M3 O4 -(O2 CEt)8 ]2
      (M = Mo, 1; W, 2). The bioxo-capped clusters Na[M3 O2 (O2 CEt)9 ] (M3 = MoW2 , W3
      ) were treated with Fe-(CO)5 , Cr(CO)6 , and Mo(CO)6 in (EtCO)2 O at 120 degrees
      C to afford Na2 M'2 -[MoW2 O4 (O2 CEt)8 ]2 (M' = Fe, 3; Cr, 4; Mo, 5) and Na2 Mo2
      [W3 O4 (O2 CEt)8 ]2 (6), respectively. The isomorphous clusters 1, 2, 5, and 6
      were characterized by X-ray crystallography. The structures, similar to those of
      the analogues Na2 Cr2 [M3 O4 -(O2 CEt)8 ] (M = Mo, 7; W, 8) and Na2 V2 [M3 O4 (O2
      CEt)8 ]2 (M = Mo, 9; W, 10), consist of two incomplete cubane-type [M3 O4 (O2
      Et)8 ](4-) units centrosymmetrically bridged by two M'(III) metal ions through MU
      oxo and propionate groups; the resulting cluster dianions are linked by Na(+)
      ions into infinite chains. Clusters 1-10 do not dissolve in water and common
      organic solvents at room temperature. Unlike the chromium(III) clusters 7 and 8,
      the iron(III) and vanadium(III) clusters 1 and 9 are soluble in aqueous acid
      solution, as a result of their decomposition into isolated [Mo3 O4 ](4+) cluster
      units. Temperature-dependent magnetic susceptibilities of 1, 2, and 7-10 were
      measured over the range 2-200 K and modeled by means of the spin-Hamiltonian H = 
      2JS1 S2 to give spin exchange coupling constants J/k of -0.60, -0.72, -1.76, 
      1.31, -4.80, and -1.46 K, respectively. These figures show that antiferromagnetic
      spin exchange coupling interactions between the magnetic, bridging M'(III) ions
      are very weak. These species show characteristic bands in the IR spectra at 740
      820 cm(-1) , which can probably be assigned to v(M-MU-O). 

PMID- 24022953
TI  - The thiazole ylide: a frequently invoked intermediate is a stable species in the
      gas phase.
AB  - The 1, 2-hydrogen shift isomers of neutral (singlet and triplet) thiazole (1) and
      its radical cation have been investigated by a combination of mass spectro-metric
      experiments and hybrid density functional theory calculations. The latter were
      used to probe the structures and stabilities of selected C3 H3 NS and C3 H3
      NS(.+) isomers and transition state structures. Although 3H-thiazole-2-ylidene
      (2) is less stable than 1, by 31.5 kcalmol(-1) , it is expected to be capable of
      independent existence, since the 1, 2-hydrogen shift from carbon to nitrogen
      involves a very large energy barrier of 72.4 kcalmol(-1) . The other 1, 2
      hydrogen shift reaction from C(2) leads not to the expected cyclic 1H-thiazole-2
      ylidene structure (3), which is apparently unstable, but rather to the ring
      opened species HSCH?CHNC (4), which is 34.5 kcalmol(-1) higher in energy than 1.
      The barrier in this case is lower but still large (54.9 kcalmol(-1) ). The
      triplet ground states of 1, 2 and 4 are considerably destabilised (69.5, 63.2 and
      58.7 kcalmol(-1) ) relative to their singlet states. Interestingly, in addition
      to 2(.+) and 4(.+) , the cyclic radical cation 3(.+) is predicted to be stable
      although it is substantially higher in energy than ionised thiazole 1(.+) (by
      53.9 kcalmol(-1) ), whereas 2(.+) and 4(.+) are much closer in energy (only 10.2
      and 27.0 kcalmol(-1) higher, respectively). Dissuading 2(.+) and 3(.+) from
      isomerising to 1(.+) are energy barriers of 52.6 and 15.3 kcalmol(-1) ,
      respectively. Experimentally, dissociative ionisation of 2-acetylthiazole enabled
      the generation of 2(.+) , which could be differentiated from 1(.+) by collisional
      activation mass spectrometry. Reduction of the ylide ion 2(.+) in neutralisation
      reionisation mass spectrometry experiments yielded the corresponding neutral
      molecule 2. This direct observation of a thiazolium ylide provides support for
      postulates of such species as discrete intermediates in a variety of biochemical
      transformations. 

PMID- 24022954
TI  - The vinylketene-acylallene rearrangement: theory and experiment.
AB  - Alkoxyvinylketenes4are generated by flash vacuum thermolysis (FVT) or photolysis
      of 3-alkoxycyclobutenones3. The thermal interconversion of4and allene carboxylic
      acid esters5under FVT conditions is demonstrated by Ar matrix FTIR spectroscopy.
      In addition, ethoxy-vinylketene4bundergoes thermal elimination of ethene with
      formation ofs-cis-ands-trans-acetylketene(8). An analogous aminovinylketene-to
      allenecarbox-amide conversion is observed on FVT of 3
      dimethylaminocyclobutenone3c. A facile 1, 3-chlorine migration in 2, 3-buta
      dienoyl chloride(5d)is also reported. Consistent with the experimental
      observations, 1, 3-methoxy, 1, 3-chloro, and 1, 3-dimethylamino migrations in
      vinylketene are calculated (G2(MP2, SVP) level) to have moderate barriers of 169,
      157, and 129 kJ mol(-1) , respectively, significantly less than the corresponding
      1, 3-H shift barrier (273 kJ mol(-1) ). The stabilization of the four-center
      transition structures is rationalized in terms of the donor-acceptor interaction
      between the lone pair electrons of the migrating donor substituent and the vacant
      central carbon p orbital of the ketene LUMO. The predicted migratory aptitude in
      the series of substituted vinylketenes, R-C(?CH2 )-CH?C?O, is in the order N(CH3
      )2 >SCH3 >SH>Cl>NH2 >OCH3 >OH>F>H>CH3 , and correlates well with the electron
      donating ability of the R group. 

PMID- 24022955
TI  - Edge-sharing SiN4 Tetrahedra in the Highly Condensed Nitridosilicate BaSi7 N10.
AB  - The novel nitridosilicate BaSi7 N10 was obtained by the reaction of barium metal
      with Si(NH)2 in a special high-frequency furnace at 1650  degrees C. The single
      crystal structure determination (a = 687.29(3), b = 671.29(3), c = 963.28(4) pm,
      beta = 106.269(3) degrees , PC, Z = 2, R1 = 0.0497, wR2 = 0.0924) reveals a
      network structure of connected SiN4 tetrahedra. BaSi7 N10 is the first
      nitridosilicate with both corner and edge-sharing SiN4 tetrahedra. Unlike the
      situation in normal oxosilicates, vertex-sharing of SiN4 tetrahedra is not
      exclusively favored over edge-sharing. With a Si:N molar ratio of 7:10, BaSi7 N10
      is the most highly condensed multinary nitridosilicate known and has almost the
      same degree of condensation as binary Si3 N4 . 

PMID- 24022956
TI  - Evidence for Direct trans Insertion in a Hydrido-Olefin Rhodium Complex-Free
      Nitrogen as a Trap in a Migratory Insertion Process.
AB  - Reduction of the hydrido chloride complex [Rh(H)Cl{CH3 C(CH2 CH2 -P(tBu)2 )2 }]
      (4) with NaH under a nitrogen atmosphere results in formation of two products:
      the dinitrogen complex [Rh(N2 )-{CH3 C(CH2 P(tBu)2 )2 }] (2) and the unusual low
      valent hydrido-olefin complex, [RhH{CH2 ?C(CH2 CH2 P(tBu)2 )2 }] (3). In the
      presence of N2 , complexes 2 and 3 are in equilibrium in solution; 2 is about
      2.9kcalmol(-1) more stable than 3 + N2 . Both complexes co-crystallize in the
      solid state; they occupy the same crystallographic site in the crystal lattice
      (P2-(1)/c; Z = 4; a = 12.173(2), b = 14.121 (3), c = 15.367 (3); alpha = 90, beta
      = 106.50(3), gamma = 90 degrees ). The mechanism of the reversible
      interconversion of 2 and 3 has been studied in detail. Complex 3 undergoes rapid
      olefin insertion/beta-hydrogen elimination processes. The insertion rates were
      measured at different temperatures by saturation transfer NMR experiments,
      providing evidence for a highly organized late transition state (deltaS?~? - 40
      e.u.), which can be caused by a concerted "trans migration". This theoretically
      unfavorable process is assisted by a distortion from the ideal square-planar
      configuration, including a decrease of the P-Rh-P angle and some bias of the
      double bond toward the hydride as indicated by the X-ray crystal structure of 3.
      Under a nitrogen atmosphere, the intermediate formed upon olefin insertion is
      slowly trapped by free dinitrogen to form complex 2. The dinitrogen dissociation
      from 2 was found to be the rate-determining step for the overall interconversion
      of 2 and 3 (deltaG?298 = 24.1 kcalmol(-1) ). 

PMID- 24022957
TI  - On the role of structural zinc in bis(cysteinyl) protein sequences.
AB  - Besides its functional role in many hydrolytic metalloenzymes, zinc acts as a
      structural component by being attached to bis(cysteinyl) protein sequences in
      some of the same enzymes, and in other metalloproteins and zinc fingers, and by
      being an essential constituent in metallothioneins. It is not always obvious
      whether the zinc-binding proteins are pre-organized for the incorporation of the
      metal or whether the zinc ion provides the structurizing power and stability for
      the observed peptide conformations. We have addressed the coordination chemistry
      aspects of this question by synthesizing zinc complexes of small model peptides
      and by determining their structures in solution by 2D NMR spectroscopy. The
      peptides chosen were of the terminally protected bis(cysteinyl) type: Cys-Cys,
      Cys-Gly-Cys, Cys-Phe-Cys, and Cys-Gly-Ile-Cys. The zinc ions fold these peptides
      into structures that can be superimposed on those of the natural proteins. 

PMID- 24022958
TI  - Nickel complexes of 21-oxaporphyrin and 21, 23-dioxaporphyrin.
AB  - The nickel(I) and nickel(II) complexes of 5,20-bis(p-tolyl)-10, 15-diphenyl-21
      oxaporphyrin (ODTDPPH) and 5,10,15,20-tetraphenyl-21, 23-dioxaporphyrin (O2 TPP)
      have been investigated. These oxa analogues of 5,10,15,20-tetraarylporphyrin,
      where one or two pyrrole rings are replaced by a furan moiety, have been
      synthesized by condensation of the respective precursors, namely 2,5
      bis(arylhydroxymethyl)furan, pyrrole, and arylaldehyde. Insertion of nickel(II)
      into ODTDPPH or O2 TPP yielded high-spin five- and six-coordinate
      ([(ODTDPP)Ni(II) Cl] and [(O2 TPP)NiIICl2 ]) complexes, which can be reduced with
      moderate reducing reagents. The EPR spectra of [(ODTDPP)Ni(I) ] and [(O2
      TPP)Ni(I) Cl] revealed the Ni(I) oxa(dioxa)porphyrin rather than a Ni(I) anion
      radical electronic structure. In the structures of [(ODTDPP)Ni(II) Cl], [(O2
      TPP)Ni(IICl) 2 ], and [(ODTDPP)Ni(I) ], determined by X-ray diffraction, the
      furan ring is planar and coordinates in the eta(1) fashion through the trigonal
      oxygen atom; the nickel ion lies in the furan plane for the latter two complexes,
      but slightly outside it in [(ODTDPP)Ni(II) Cl]. The Ni-N and Ni-O bond lengths
      decrease upon reduction of high-spin five-coordinate [(ODTDPP)Ni(II) Cl] to four
      coordinate [(ODTDPP)Ni(I) ]. The pattern of downfield pyrrole resonances in (1) H
      NMR spectra of [(ODTDPP)Ni(IICl) ] and [(O2 TPP)-Ni(II) Cl2 ] has been
      established. The downfield positions of furan resonances are unusual for Ni(II)
      heteroporphyrins; they have been accounted for by the nearly in-plane
      coordination of the furan moiety as opposed to the side-on coordination found for
      thiophene- or selenophene-containing heteroporphyrins. An example of ion-pair
      formation, [(O2 TPPH)2 ][Ni(II) Cl4 ], was produced from [(O2 TPP)Ni(II) Cl2 ] by
      acidification with HCl. 

PMID- 24022959
TI  - Structural Effects in the Reductive Activation of (Indenyl)RhL2 Complexes: The
      Reduction of [Rh(eta(5) -C9 H7 )(eta(4) -cod)].
AB  - The reduction of the indenyl complex [Rh(eta(5) -C9 H7 )(eta(4) -cod)] has been
      investigated in the context of structural effects induced by the transfer of one
      electron. The reduction of this complex occurs in two steps, leading first to the
      radical anion and then to the highly frangible dianion. Both species eliminate
      the indenyl anion. In the presence of free cyclooctadiene, the related cleavage
      leading to the indenyl anion and bis-cyclooctadiene rhodium fragments now follows
      a Michaelis-Menten-type mechanism involving precoordination of one extra COD
      ligand to the initial radical anion. These results suggest the modification of
      the hapticity of the indenyl ligand in connection with 17- and 19-electron
      metalcentered intermediates. 

PMID- 24022960
TI  - A Joint Experimental and Theoretical Study of the Interaction between Aluminum
      and Electroluminescent Polymers: Cyano Derivatives of Poly(p-phenylene vinylene).
AB  - The early stages of metal/polymer interface formation between aluminum and
      poly(2,5,2',5'-tetrahexyloxy-8,7'-dicyanodi-p-phenylenevinylene) or their ring
      substituted derivatives have been studied theoretically by using quantum-chemical
      calculations as well as experimentally by X-ray photoelectron spectroscopy and
      ultraviolet photoelectron spectroscopy. This class of conjugated polymer is of
      interest in the development of organic light-emitting diodes. The theoretical and
      experimental results indicate that aluminum preferentially reacts with the
      polymer by forming covalent bonds with the nitrogen and carbon atoms of the cyano
      groups. When the side chains of the phenylene rings include carbonyl groups,
      however, the theoretical results indicate that the carbonyl moiety is another
      preferred site of interaction. 

PMID- 24022961
TI  - Quantum-Chemical Investigations of Stabilizing Interactions in MU-Diborylcarbene
      Dicobalt Complexes with a Planar Tetracoordinate Carbon Atom.
AB  - Quantum-chemical methods have been employed to study the nature of stabilization
      in dinuclear cobalt complexes of the general formula [{(C5 H5 )Co}2 (MU-CR(1) 2
      BCBR(2) R(3) )] (6) as well as the "antivan't Hoff-Le Bel" configuration of the
      planar tetracoordinate carbon (ptC) atom of the bridging diborylcarbene ligand 9.
      Extended Huckel and ab initio Hartree-Fock calculations have been carried out for
      the model compounds 6b (R(1) = R(2) = R(3) = H) and 6c (R(1) = R(2) = H; R(3) =
      C6 H5 ). Ab initio electron deformation density maps and natural population
      analysis calculations show that complexes 6 are stabilized through push-pull
      effects by which the ptC experiences pi electron density delocalization and sigma
      electron density accumulation. The calculated electronic configuration of the ptC
      in the free ligand 9b is sigma(2.978) pi(1.501) , and in 6b sigma(3.944)
      pi(1.356) . Electron density donation from one cobalt atom to an aryl group on
      the bridging ligand further contributes to the stabilization of the complexes 6. 

PMID- 24022962
TI  - Extended-Core Discotic Liquid Crystals Based on the Intramolecular H-Bonding in N
      Acylated 2,2'-Bipyridine-3,3'-diamine Moieties.
AB  - A new type of disc-shaped molecule (1 a-c) has been synthesised and
      characterised. The molecules were built up by linking three lipophilic, N
      monoacylated 2,2'-bipyridine-3,3'-diamine wedges to a central 1,3,5
      benzenetricarbonyl unit. They show liquid crystalline behaviour, as shown by DSC,
      polarisation microscopy and X-ray diffraction. In all cases the mesophase was
      characterised as a Dho phase. From (1) H NMR results it was shown that the
      interior of compounds 1 a-c preferentially adopts a C3 symmetrical conformation
      owing to strong intramolecular H-bonding, which gives rise to an extended core.
      This large core induces strong interactions between molecules, leading to
      mesophases of enhanced thermal stability. 

PMID- 24022963
TI  - Phenoxyl radical complexes of gallium, scandium, iron and manganese.
AB  - The hexadentate macrocyclic ligands 1,4,7-tris(3,5-dimethyl-2-hydroxybenzyl)
      1,4,7-triazacyclononane (L CH 3H3 ), 1,4,7-tris(3,5-di-tert-butyl-2
      hydroxybenzyl)-1,4,7-triazacyclononane (L(Bu) H3 ) and 1,4,7-tris(3-tert-butyl-5
      methoxy-2-hydroxybenzyl)-1,4,7-triazacyclononane (L OCH 3-H3 ) form very stable
      octahedral neutral complexes LM(III) with trivalent (or tetravalent) metal ions
      (Ga(III) , Sc(III) , Fe(III) , Mn(III) , Mn(IV) ). The following complexes have
      been synthesized: [L(Bu) M], where M = Ga (1), Sc (2), Fe (3); [L(Bu) Mn(IV) ]PF6
      (4'); [L OCH 3M], where M = Ga (1 a), Sc (2 a), Fe (3 a); [L OCH 3Mn(IV) ]PF6 (4
      a'); [L CH 3M], where M = Sc (2 b), Fe (3 b), Mn(III) (4 b); [L CH 3Mn(IV) ]2
      (ClO4 )3 (H3 O)(H2 O)3 (4 b'). An electrochemical study has shown that complexes
      1, 2, 3, 1 a, 2 a and 3 a each display three reversible, ligand-centred, one
      electron oxidation steps. The salts [L OCH 3Fe(III) ]ClO4 and [L OCH 3Ga(III)
      ]ClO4 , have been isolated as stable crystalline materials. Electronic and EPR
      spectra prove that these oxidations produce species containing one, two or three
      coordinated phenoxyl radicals. The Mossbauer spectra of 3 a and [3 a](+) show
      conclusively that both compounds contain high-spin iron(III) central ions.
      Temperature-dependent magnetic susceptibility measurements reveal that 3 a has an
      S = 5/2 and [3a](+) an S = 2 ground state. The latter is attained through
      intramolecular antiferromagnetic exchange coupling between a high-spin iron(III)
      (S1 = 5/2) and a phenoxyl radical (S2 = 1/2) (H = - 2JS1 S2 ; J = - 80 cm(-1) ).
      The manganese complexes undergo metal- and ligand-centred redox processes, which
      were elucidated by spectroelectrochemistry; a phenoxyl radical Mn(IV) complex
      [Mn(IV) L OCH 3](2+) is accessible. 

PMID- 24022966
TI  - Wellbeing.

PMID- 24022965
TI  - Differentiation potential of limbal fibroblasts and bone marrow mesenchymal stem
      cells to corneal epithelial cells.
AB  - The cornea is covered by a stratified epithelium that is renewed by stem cells
      located in the peripheral region of the cornea known as the limbus. This stroma
      of the limbus contains stromal keratocytes that, when expanded in culture, are
      termed limbal fibroblasts (LFs). It is thought that LFs exhibit similar
      characteristics to bone marrow mesenchymal stem cells (BM MSCs) and help maintain
      the epithelial stem cell phenotype in the limbal region. In this study, we aimed
      at reprogramming stage-specific embryonic antigen-4 (SSEA4+) LFs and BM MSCs into
      corneal epithelial lineage using a three-dimensional culture system and embryonic
      stem cell medium. After enrichment, SSEA4+ cells showed a higher level of stem
      cell marker expression such as Sox2, Oct4, Nanog, Rex1, ABCG2, and TRA-1-60, and
      colony-forming efficiency than did SSEA4- cells. SSEA4+, as compared to SSEA4-
      cells, had a greater propensity to form spheres that, in turn, were induced into
      ectodermal lineage and further differentiated into functional corneal epithelium.
      Results show that LFs were similar to BM MSCs in marker profiles, and together
      with the differences noted between SSEA4+ and SSEA4- cells, point to LFs' being
      tissue-specific MSCs. However, LFs showed a greater potential for differentiation
      into corneal epithelium, indicating the potential importance of tissue-specific
      adult progenitors in their reprogramming capacity into cells of interest. This
      study opens a new avenue for investigating the molecular mechanism involved in
      maintaining a limbal stem cell niche and thus a potentially important clinical
      application to treat corneal epithelial stem cell loss.

PMID- 24022972
TI  - Youth Health Champions.

PMID- 24022973
TI  - The remarkable Dr John Snow.

PMID- 24022974
TI  - Healthy young minds, healthy communities.

PMID- 24022975
TI  - Behaviour change and public health interventions.

PMID- 24022976
TI  - Volunteering and managing change in the health sector.

PMID- 24022977
TI  - How can 21st century public health research overcome the long-standing
      frustration associated with dietary assessment?

PMID- 24022978
TI  - Cervical cancer prevention campaign using an integrated marketing communication
      approach in Korea.

PMID- 24022979
TI  - Strengthening the role of caregivers in promoting fall-risk screening for older
      adults during the annual wellness visit.

PMID- 24022982
TI  - LTMap: a web server for assessing the potential liver toxicity by genome-wide
      transcriptional expression data.
AB  - Toxicogenomics (TGx) has played a significant role in mechanistic research
      related with hepatotoxicity as well as liver toxicity prediction. Currently,
      several large-scale preclinical TGx data sets were made freely accessible to the
      public, such as Open TG-GATEs. With the availability of a sufficient amount of
      microarray data, it is important to integrate this information to provide new
      insights into the risk assessment of potential drug-induced liver toxicity. Here
      we developed a web server for evaluating the potential liver toxicity based on
      genome-wide transcriptomics data, namely LTMap. In LTMap, researchers could
      compare signatures of query compounds against a pregenerated signature database
      of 20 123 Affymetrix arrays associated with about 170 compounds retrieved from
      the largest public toxicogenomics data set Open TG-GATEs. Results from this
      comparison may lead to the unexpected discovery of similar toxicological
      responses between chemicals. We validated our computational approach for
      similarity comparison using three example drugs. Our successful applications of
      LTMap in these case studies demonstrated its utility in revealing the connection
      of chemicals according to similar toxicological behaviors. Furthermore, a user
      friendly web interface is provided by LTMap to browse and search toxicogenomics
      data (http://tcm.zju.edu.cn/ltmap).

PMID- 24022984
TI  - Exploring the use of a Facebook page in anatomy education.
AB  - Facebook is the most popular social media site visited by university students on
      a daily basis. Consequently, Facebook is the logical place to start with for
      integrating social media technologies into education. This study explores how a
      faculty-administered Facebook Page can be used to supplement anatomy education
      beyond the traditional classroom. Observations were made on students' perceptions
      and effectiveness of using the Page, potential benefits and challenges of such
      use, and which Insights metrics best reflect user's engagement. The Human Anatomy
      Education Page was launched on Facebook and incorporated into anatomy resources
      for 157 medical students during two academic years. Students' use of Facebook and
      their perceptions of the Page were surveyed. Facebook's "Insights" tool was also
      used to evaluate Page performance during a period of 600 days. The majority of in
      class students had a Facebook account which they adopted in education. Most
      students perceived Human Anatomy Education Page as effective in contributing to
      learning and favored "self-assessment" posts. The majority of students agreed
      that Facebook could be a suitable learning environment. The "Insights" tool
      revealed globally distributed fans with considerable Page interactions. The use
      of a faculty-administered Facebook Page provided a venue to enhance classroom
      teaching without intruding into students' social life. A wider educational use of
      Facebook should be adopted not only because students are embracing its use, but
      for its inherent potentials in boosting learning. The "Insights" metrics analyzed
      in this study might be helpful when establishing and evaluating the performance
      of education-oriented Facebook Pages.

PMID- 24022983
TI  - The International ADHD in Substance Use Disorders Prevalence (IASP) study:
      background, methods and study population.
AB  - Attention deficit/hyperactivity disorder (ADHD) is an increasingly recognized
      comorbid condition in subjects with substance use disorders (SUDs). This paper
      describes the methods and study population of the International ADHD in Substance
      Use Disorders Prevalence (IASP) study. Objectives of the IASP are to determine
      the prevalence of ADHD in adult treatment seeking patients with SUD in different
      countries and SUD populations, determine the reliability and validity of the
      Adult ADHD Self-report Scale V 1.1 (ASRS) as ADHD screening instrument in SUD
      populations, investigate the comorbidity profile of SUD patients with and without
      ADHD, compare risk factors and protective factors in SUD patients with and
      without a comorbid diagnosis of ADHD, and increase our knowledge about the
      relationship between ADHD and the onset and course of SUD. In this cross
      sectional, multi-centre two stage study, subjects were screened for ADHD with the
      ASRS, diagnosed with the Conner's Adult ADHD Diagnostic Interview for DSM-IV
      (CAADID), and evaluated for SUD, major depression, bipolar disorder, anti social
      personality disorder and borderline personality disorder. Three thousand five
      hundred and fifty-eight subjects from 10 countries were included. Of these 40.9%
      screened positive for ADHD. This is the largest international study on this
      population evaluating ADHD and comorbid disorders.

PMID- 24022985
TI  - Superfluorescent squaraine with efficient two-photon absorption and high
      photostability.
AB  - The synthesis, linear photophysical, two-photon absorption (2PA), femtosecond
      transient absorption, and superfluorescence properties of a new symmetrical
      squaraine derivative (1) are reported. Steady-state linear spectral and
      photochemical properties, fluorescence lifetimes, and excitation anisotropy of 1
      were investigated in various organic solvents. High fluorescence quantum yields
      (~0.7) and very high photostability (photodecomposition quantum yields ~10(-6)
      10(-8)) were observed. An open-aperture Z-scan method was used to obtain 2PA
      spectra of 1 over a broad spectral range (maximum 2PA cross section ~1000 GM).
      Excited-state absorption (ESA) and gain was observed by femtosecond transient
      absorption spectroscopy, in which both reached a maximum at approximately 500 fs.
      Squaraine 1 exhibits efficient superfluorescence. The quantum chemical study of 1
      revealed the simulated vibronic nature of the 1PA and 2PA spectra were in good
      agreement with experimental data; this may provide the ability to predict
      potential advanced photonic materials.

PMID- 24022986
TI  - Is there subclinical synovitis in early psoriatic arthritis? A clinical
      comparison with gray-scale and power Doppler ultrasound.
AB  - OBJECTIVE: Arthritis activity assessments in psoriatic arthritis (PsA) have
      traditionally relied on tender and swollen joint counts, but in rheumatoid
      arthritis, multiple studies have demonstrated subclinical inflammation using
      modern imaging. The aim of this study was to compare clinical examination and
      ultrasound (US) findings in an early PsA cohort. METHODS: Forty-nine disease
      modifying antirheumatic drug-naive patients with recent-onset PsA (median disease
      duration 10 months) underwent gray-scale (GS) and power Doppler (PD) US of 40
      joints plus tender and swollen joint counts of 68/66 joints. GS and PD were
      scored on a 0-3 semiquantitative scale for each joint. Clinically active joints
      were defined as tender and/or swollen and US active joints were defined as a GS
      score >=2 and/or a PD score >=1. RESULTS: The most common sites for subclinical
      synovitis were the wrist (30.6%), knee (21.4%), metatarsophalangeal (MTP) joints
      (26.5-33.7%), and metacarpophalangeal joints (10.2-19.4%). Excluding MTP joints
      and ankles, 37 (75.5%) of 49 patients had subclinical synovitis with a median of
      3 (interquartile range [IQR] 1-4) joints involved. In contrast, clinical
      overestimation of synovitis occurred most commonly at the shoulder (38%) and
      ankle (28.6%). Twelve of 49 patients were classified clinically as having
      oligoarthritis; of these, subclinical synovitis identified 8 (75%) as having
      polyarthritis with an increase in their median joint count from 3 (IQR 1-4) to 6
      (IQR 5-7). CONCLUSION: This study has demonstrated that subclinical synovitis, as
      identified by US, is very common in early PsA and led to the majority of
      oligoarthritis patients being reclassified as having polyarthritis. Further
      research is required into the relationship of such subclinical synovitis to
      structural progression.

PMID- 24022987
TI  - A novel double carbonylation reaction of aryl halides: selective synthesis of 5
      arylfuranones.
AB  - Double CO inCOrporation: An atom-efficient synthesis of 4-arylfuranones from aryl
      halides, two molecules of CO, and terminal alkenes is reported (see scheme). 18
      different 4-arylfuranones were synthesized in up to 83 % yield in a
      straightforward manner and with high regioselectivity. The range of the new 4
      arylfuranones synthesized demonstrates the value and novelty of this procedure.

PMID- 24022989
TI  - Autonomic responses to social and nonsocial pictures in adolescents with autism
      spectrum disorder.
AB  - It remains unclear why individuals with autism spectrum disorder (ASD) tend to
      respond in an atypical manner in social situations. Investigating autonomic and
      subjective responses to social vs. nonsocial stimuli may help to reveal
      underlying mechanisms of these atypical responses. This study examined autonomic
      responses (skin conductance level and heart rate) and subjective responses to
      social vs. nonsocial pictures in 37 adolescents with an ASD and 36 typically
      developing (TD) adolescents. Thirty-six pictures from the International Affective
      Picture System were presented, divided into six categories based on social
      content (social vs. nonsocial) and pleasantness (pleasant, neutral, and
      unpleasant). Both in adolescents with ASD as well as TD adolescents, pictures
      with a social content resulted in higher skin conductance responses (SCRs) for
      pleasant and unpleasant pictures than for neutral pictures. No differences in
      SCRs were found for the three nonsocial picture categories. Unpleasant pictures,
      both with and without a social content, showed more heart rate deceleration than
      neutral pictures. Self-reported arousal ratings were influenced by the social and
      affective content of a picture. No differences were found between individuals
      with ASD and TD individuals in their autonomic and subjective responses to the
      picture categories. These results suggest that adolescents with ASD do not show
      atypical autonomic or subjective responses to pictures with and without a social
      content. These findings make it less likely that impairments in social
      information processing in individuals with ASD can be explained by atypical
      autonomic responses to social stimuli.

PMID- 24022988
TI  - Priming with ligands secreted by human stromal progenitor cells promotes grafts
      of cardiac stem/progenitor cells after myocardial infarction.
AB  - Transplantation of culture-expanded adult stem/progenitor cells often results in
      poor cellular engraftment, survival, and migration into sites of tissue injury.
      Mesenchymal cells including fibroblasts and stromal cells secrete factors that
      protect injured tissues, promote tissue repair, and support many types of
      stem/progenitor cells in culture. We hypothesized that secreted factors in
      conditioned medium (CdM) from adult bone marrow-derived multipotent stromal cells
      (MSCs) could be used to prime adult cardiac stem/progenitor cells (CSCs/CPCs) and
      improve graft success after myocardial infarction (MI). Incubation of adult rat
      CPCs in CdM from human MSCs isolated by plastic adherence or by magnetic sorting
      against CD271 (a.k.a., p75 low-affinity nerve growth factor receptor; p75MSCs)
      induced phosphorylation of STAT3 and Akt in CPCs, supporting their proliferation
      under normoxic conditions and survival under hypoxic conditions (1% oxygen).
      Priming CSCs with 30* p75MSC CdM for 30 minutes prior to transplantation into
      subepicardial tissue 1 day after MI markedly increased engraftment compared with
      vehicle priming. Screening CdM with neutralizing/blocking antibodies identified
      connective tissue growth factor (CTGF) and Insulin as key factors in p75MSC CdM
      that protected CPCs. Human CTGF peptide (CTGF-D4) and Insulin synergistically
      promoted CPC survival during hypoxia in culture. Similar to CdM priming, priming
      of CSCs with CTGF-D4 and Insulin for 30 minutes prior to transplantation promoted
      robust engraftment, survival, and migration of CSC derivatives at 1 week and 1
      month after MI. Our results indicate that short-term priming of human CSCs with
      CTGF-D4 and Insulin may improve graft success and cardiac regeneration in
      patients with MI.

PMID- 24022990
TI  - Studying epigenetic DNA modifications in undergraduate laboratories using
      complementary bioinformatic and molecular approaches.
AB  - Epigenetic inheritance is the inheritance of genetic information that is not
      based on DNA sequence alone. One type of epigenetic information that has come to
      the forefront in the last few years is modified DNA bases. The most common
      modified DNA base in nature is 5-methylcytosine. Herein, we describe a laboratory
      experiment that combines bioinformatic and molecular approaches to study the
      presence and abundance of 5-methylcytosine in different organisms. Students were
      originally provided with the protein sequence of the Xenopus laevis DNMT1
      cytosine-5 DNA methyltransferase and used BLASTP searches to detect the presence
      of protein orthologs in the genomes of several organisms including Homo sapiens,
      Mus musculus, Plasmodium falciparum, Drosophila melanogaster, Saccharomyces
      cerevisiae, Arabidopsis thaliana, and Caenorhabditis elegans. Students generated
      hypotheses regarding the presence and abundance of 5-methylcytosine in these
      organisms based on their bioinformatics data, and directly tested their
      predictions on a subset of DNAs using restriction enzyme isoschizomer assays. A
      southern blotting assay to answer the same question is also presented. In
      addition to exposure to the field of epigenetics, the strengths of the laboratory
      are students are able to make predictions using bioinformatic tools and quickly
      test them in the laboratory. In addition, students are exposed to two potential
      misinterpretations of bioinformatic search data. The laboratory is easily
      modified to incorporate outside research interests in epigenetics.

PMID- 24022991
TI  - Synthesis and anti-Plasmodium activity of benzimidazole analogues structurally
      related to astemizole.
AB  - A series of compounds structurally related to astemizole were designed and
      synthesized with the goal of determining their anti-Plasmodium activity. Several
      modifications of the astemizole structure, namely the removal of the 4
      fluorobenzyl and/or 4-methoxyphenethyl moieties, substitution of the benzene ring
      of the benzimidazole scaffold, replacement of the fluorine atom in the 4
      fluorobenzyl group, and variation of the 4-aminopiperidine moiety, were explored.
      In vitro evaluation of the anti-Plasmodium activity of these compounds using the
      ItG strain showed that astemizole and some of its structurally similar
      derivatives have IC50 values in the nanomolar range and exhibit toxicity towards
      the parasite over Chinese ovarian hamster (CHO) cells with a selectivity as high
      as 200. The presence of a secondary cyclic amine at position 2 and substitution
      with chlorine at positions 4 and 5 in the benzimidazole moiety are two
      modifications that resulted in potent and selective antimalarials based on
      astemizole. 

PMID- 24022992
TI  - Pilot study of reproductive health counseling in a pediatric rheumatology clinic.
AB  - Objective: To assess perception and behavior after reproductive health counseling
      among adolescent patients in a tertiary care-based pediatric rheumatology clinic.
      Methods: Adolescent females seen at Stanford pediatric rheumatology clinic were
      prospectively enrolled during routine visits. At study start, standard clinic
      procedures for the following were reviewed with providers: 1) HEADSS (home,
      education, activities, drugs, sexual activity, and suicide/depression)
      assessment; 2) reproductive health counseling; and 3) medical record
      documentation. Patients were enrolled if providers indicated that they performed
      HEADSS assessment and reproductive health counseling. At enrollment, patients
      completed a survey to assess perceptions of reproductive health counseling. Chart
      review confirmed documented discussions. Follow-up survey 3-5 months after
      enrollment tracked reproductive health information seeking behavior. Results:
      Ninety females (ages 17 +/- 2 years old) participated. Almost all patients (99%)
      agreed that reproductive health was discussed. Seventy-one percent reported that
      pregnancy risks were discussed, 42% had recent concerns about reproductive
      health, and 33% reported their provider recommended that they seek further
      reproductive health care. Eighty-four patients completed follow-up phone surveys,
      with 25% reporting seeking further information on reproductive health concerns
      but merely 9.5% actually sought further care. Only 18% reported having ever asked
      their rheumatology provider for guidance regarding reproductive health care
      concerns. Conclusion: Routine reproductive health discussion and counseling are
      necessary in a rheumatology clinic; as in our experience, a substantial number of
      adolescents have concerns and actively seek reproductive health information.
      Despite these discussions, teens rarely pursued further reproductive health care.
      Further work to bridge this gap is needed.

PMID- 24022993
TI  - How does whisky lower serum urate level?
AB  - Clinical studies have shown that moderate whisky consumption increased renal
      excretion of urate into urine and decreased serum urate level, but the mechanism
      involved has not been established. Because renal reabsorption influences serum
      urate level, the effects of the whisky congeners on urate transporters, urate
      transporter 1 (URAT1), and voltage-driven urate transporter (URATv1) involved in
      reabsorptive transport of urate were examined. In transporter-expressing Xenopus
      oocytes, 12-year-old and 18-year-old whisky congeners inhibited urate uptake by
      URAT1 with IC50 values of 0.08 +/- 0.01 and 0.04 +/- 0.01 mg/mL, respectively,
      while urate uptake by URATv1 was inhibited only at 1 mg/mL. Decreased serum urate
      level after whisky consumption may be mainly due to inhibition of URAT1 by the
      congeners.

PMID- 24022994
TI  - Brief report: The lincRNA Hotair is required for epithelial-to-mesenchymal
      transition and stemness maintenance of cancer cell lines.
AB  - Hotair is a member of the recently described class of noncoding RNAs called
      lincRNA (large intergenic noncoding RNA). Various studies suggest that Hotair
      acts regulating epigenetic states by recruiting chromatin-modifying complexes to
      specific target sequences that ultimately leads to suppression of several genes.
      Although Hotair has been associated with metastasis and poor prognosis in
      different tumor types, a deep characterization of its functions in cancer is
      still needed. Here, we investigated the role of Hotair in the scenario of
      epithelial-to-mesenchymal transition (EMT) and in the arising and maintenance of
      cancer stem cells (CSCs). We found that treatment with TGF-beta1 resulted in
      increased Hotair expression and triggered the EMT program. Interestingly,
      ablation of Hotair expression by siRNA prevented the EMT program stimulated by
      TGF-beta1, and also the colony-forming capacity of colon and breast cancer cells.
      Furthermore, we observed that the colon CSC subpopulation (CD133(+)/CD44(+))
      presents much higher levels of Hotair when compared with the non-stem cell
      subpopulation. These results indicate that Hotair acts as a key regulator that
      controls the multiple signaling mechanisms involved in EMT. Altogether, our data
      suggest that the role of Hotair in tumorigenesis occurs through EMT triggering
      and stemness acquisition.

PMID- 24022995
TI  - Do children with autism re-enact object movements rather than imitate
      demonstrator actions?
AB  - It has been suggested that autism-specific imitative deficits may be reduced or
      even spared in object-related activities. However, most previous research has not
      sufficiently distinguished object movement reenactment (learning about the ways
      in which object move) from imitation (learning about the topography of
      demonstrated actions). Twenty children with autism (CWA) and 20 typically
      developing children (TDC) were presented with puzzle boxes containing prizes.
      Test objects and experimental conditions were designed to isolate object- and
      action-related aspects of demonstrations. There were four types of video
      demonstrations: (a) a full demonstration by an adult; (b) a ghost demonstration
      with object movements alone; (c) mimed solutions demonstrated adjacent to the
      objects; and (d) random actions performed on the surface of the objects. There
      were no significant between-group differences in the degree to which CWA and TDC
      matched the full demonstrations, the actual demonstrations or in their times to
      first solution in any of the conditions. Although there was no clear imitative
      deficit in the CWA, regression analyses were conducted to explore in more detail
      whether diagnosis, verbal intelligence quotient (VIQ), nonverbal IQ NVIQ, age or
      motor coordination predicted performance. The results are discussed in relation
      to the use of extrinsic vs. intrinsic rewards and the interplay between motor
      coordination and the relative rigidity vs. pliability of objects.

PMID- 24022997
TI  - Cadmium impairment of reproduction in the female wall lizard Podarcis sicula.
AB  - The exposure to environmental toxicants such cadmium (Cd) is an important
      research area in wildlife protection. In this study, the effect of Cd oral
      administration on the ovarian structure and function and on reproductive
      performance of the Italian wall lizard Podarcis sicula was studied. In vivo,
      adult female lizards were randomly assigned to three groups. Cd was given with
      food in single dose and in multiple doses 3 days/week for 4 weeks at dose of 1.0
      MUg/g body weight. Following euthanasia, the ovaries were removed and analyzed
      for morpho-functional changes. Results demonstrated that Cd increases
      prefollicular germ cells number; the evaluation of the number of follicles
      detects significantly higher number of atretic growing follicles, whereas primary
      follicles remain unchanged with respect to controls. After Cd treatments,
      follicles are deformed by the presence of large protrusions and a general
      dysregulation in the follicle organization is observed. The zona pellucida is
      also affected. Cd causes alteration in sugar metabolism and in metallothionein
      gene expression. Finally, Cd administration significantly reduces clutch size and
      dramatically increases embryo mortality. In conclusion, data here described show
      that Cd induces morpho-functional alterations in lizard follicles and indicates
      that these are responsible for a significant impairment of oogenesis. The effects
      of the dose are time independent, persisting essentially unchanged regardless of
      single or multiple administration, so it can be concluded that even occasional,
      sublethal Cd contamination may significantly impair reproductive performance in
      these animals.

PMID- 24022996
TI  - Structure-guided design affirms inhibitors of hepatitis C virus p7 as a viable
      class of antivirals targeting virion release.
AB  - Current interferon-based therapy for hepatitis C virus (HCV) infection is
      inadequate, prompting a shift toward combinations of direct-acting antivirals
      (DAA) with the first protease-targeted drugs licensed in 2012. Many compounds are
      in the pipeline yet primarily target only three viral proteins, namely, NS3/4A
      protease, NS5B polymerase, and NS5A. With concerns growing over resistance,
      broadening the repertoire for DAA targets is a major priority. Here we describe
      the complete structure of the HCV p7 protein as a monomeric hairpin, solved using
      a novel combination of chemical shift and nuclear Overhauser effect (NOE)-based
      methods. This represents atomic resolution information for a full-length virus
      coded ion channel, or "viroporin," whose essential functions represent a
      clinically proven class of antiviral target exploited previously for influenza A
      virus therapy. Specific drug-protein interactions validate an allosteric site on
      the channel periphery and its relevance is demonstrated by the selection of
      novel, structurally diverse inhibitory small molecules with nanomolar potency in
      culture. Hit compounds represent a 10,000-fold improvement over prototypes,
      suppress rimantadine resistance polymorphisms at submicromolar concentrations,
      and show activity against other HCV genotypes. CONCLUSION: This proof-of
      principle that structure-guided design can lead to drug-like molecules affirms p7
      as a much-needed new target in the burgeoning era of HCV DAA.

PMID- 24022998
TI  - In vivo examination of the genotoxicity of the urban air and surface soil
      pollutant, 3,6-dinitrobenzo[e]pyrene, with intraperitoneal and intratracheal
      administration.
AB  - 3,6-Dinitrobenzo[e]pyrene (3,6-DNBeP) was identified as a new potent mutagen
      toward Salmonella strains in surface soil and airborne particles. Because data of
      in vivo examination of the genotoxicity of 3,6-DNBeP are limited, micronucleus
      test was performed in peripheral blood and bone marrow, and comet assay in the
      lungs of mice treated with 3,6-DNBeP. In male ICR mice intraperitoneally (i.p.)
      injected with 3,6-DNBeP, the frequency of micronuclated polychromatic
      erythrocytes (MNPCEs) was increased in the peripheral blood and bone marrow after
      24 h in a dose-dependent manner. Compared to controls, the highest dose of 3,6
      DNBeP (40 mg/kg B.W.) induced 7.3- and 8.7-fold increases of MNPCE frequency in
      the peripheral blood and bone marrow, respectively. Furthermore, when 3,6-DNBeP
      was intratracheally (i.t.) instilled to male ICR mice, 3,6-DNBeP at the highest
      dose of 0.1 mg/kg body exhibited 3.1-fold increase of DNA tail moment in the
      lungs at 3 h after the instillation compared to controls. The values of DNA tail
      moment at 9 and 24 h after the instillation were increased up to 3.5 and 4.2
      fold, respectively. These data indicate that 3,6-DNBeP is genotoxic to mammalians
      in in vivo and suggest that 3,6-DNBeP may be a carcinogenic compound present in
      the human environment.

PMID- 24022999
TI  - Indium chloride-induced micronuclei via reactive oxygen species in Chinese
      hamster lung fibroblast V79 cells.
AB  - We study the cytotoxicity of indium chloride (InCl3) in Chinese hamster lung
      fibroblasts, the V79 cells, using MTT assay. The results showed that InCl3 did
      not induce significant cytotoxicity at various concentrations tested. In
      addition, the frequency of micronuclei (MN) was assayed to evaluate the genotoxic
      effects of InCl3 in V79 cells. InCl3 at concentrations ranged 0.1-1 MUM
      significantly increased MN frequency in a concentration-dependent manner. Both
      catalase and superoxide dismutase at concentrations of 75 and 150 MUg/mL
      significantly inhibited InCl3-induced MN. Similarly, Germanium oxide (GeO2) and
      dimercaprol expressed antigenotoxic effects. From these findings, it is concluded
      that InCl3 is a potent genotoxic chemical, which may be mediated partly by
      inducing oxidative stress. The significance of this study shows that the workers
      in the semiconductor factories should be cautious in exposing to the hazardous
      genotoxic InCl3.

PMID- 24023000
TI  - Dissociation of antimicrobial and hemolytic activities of gramicidin S through N
      methylation modification.
AB  - beta-Sheet antimicrobial peptides (AMPs) are well recognized as promising
      candidates for the treatment of multidrug-resistant bacterial infections. To
      dissociate antimicrobial activity and hemolytic effect of beta-sheet AMPs, we
      hypothesize that N-methylation of the intramolecular hydrogen bond(s)-forming
      amides could improve their specificities for microbial cells over human
      erythrocytes. We utilized a model beta-sheet antimicrobial peptide, gramicidin S
      (GS), to study the N-methylation effects on the antimicrobial and hemolytic
      activities. We synthesized twelve N-methylated GS analogues by replacement of
      residues at the beta-strand and beta-turn regions with N-methyl amino acids, and
      tested their antimicrobial and hemolytic activities. Our experiments showed that
      the HC50 values increased fivefold compared with that of GS, when the internal
      hydrogen-bonded leucine residue was methylated. Neither hemolytic effect nor
      antimicrobial activity changed when proline alone was replaced with N
      methylalanine in the beta-turn region. However, analogues containing N
      methylleucine at beta-strand and N-methylalanine at beta-turn regions exhibited a
      fourfold increase in selectivity index compared to GS. We also examined the
      conformation of these N-methylated GS analogues using (1)H NMR and circular
      dichroism (CD) spectroscopy in aqueous solution, and visualized the backbone
      structures and residue orientations using molecular dynamics simulations. The
      results show that N-methylation of the internal hydrogen bond-forming amide
      affected the conformation, backbone shape, and side chain orientation of GS.

PMID- 24023001
TI  - Societal costs of rheumatoid arthritis in China: a hospital-based cross-sectional
      study.
AB  - OBJECTIVE: To estimate the annual direct and indirect costs of rheumatoid
      arthritis (RA) in China and identify the predictors for cost of illness. METHODS:
      A cross-sectional study of cost of illness from the societal perspective was
      conducted on 829 patients with RA in 21 tertiary care hospitals in China between
      July 2009 and December 2010. Data on demographics, clinical variables, and
      components of costs were collected by physician interview. Costs were represented
      in 2009 US dollars using purchasing power parity estimates. Univariate and
      multivariate linear regression analyses were performed to identify the predictors
      for cost of illness. RESULTS: The mean +/- SD total cost of RA in China was
      $3,826 +/- $5,659 per patient-year, given a gross domestic product per capita of
      $6,798 in China in 2009. Direct costs and indirect costs comprised 90.0% and
      10.0% of the total costs, respectively. Drug expense represented approximately
      half of the total costs, dominated by biologic agents (48.2%) and disease
      modifying antirheumatic drugs (23.5%). Additionally, the cost of extracted herbal
      drugs and traditional Chinese medicine comprised ~17.6% of the drug expense.
      Higher education level, noninsured status, longer disease duration, more
      extraarticular manifestations, and higher Health Assessment Questionnaire score
      independently predicted higher total costs. CONCLUSION: Our results provide the
      first study of costs of RA in China. This study not only demonstrates the
      economic burden of RA, but also identifies the predictors that could be
      interventional factors to reduce the societal costs of RA in China.

PMID- 24023002
TI  - Antimutagenic potential and modulation of carcinogen-metabolizing enzymes by
      ginger essential oil.
AB  - Essential oil extracted from ginger (GEO) was evaluated for its mutagenicity to
      Salmonella typhimurium TA 98, TA 100, TA 102, and TA 1535 strains with and
      without microsomal activation. GEO was found to be non-mutagenic up to a
      concentration of 3 mg/plate. It was also assessed for antimutagenic potential
      against direct acting mutagens such as sodium azide, 4-nitro-o-phenylenediamine,
      N-methyl-N'-nitro-N-nitrosoguanidine, tobacco extract, and 2-acetamidoflourene,
      which needs microsomal activation. GEO significantly inhibited (p < 0.001) the
      mutagenicity induced by these agents in a concentration-dependent manner. The
      effect of GEO to modulate the action of phase I carcinogen-metabolizing enzymes
      was investigated by studying its effect on various isoforms of microsomal
      cytochrome P450 enzymes. Significant inhibition of CYP1A1, CYP1A2, and CYP2B1/2,
      aniline hydroxylase (an indicator of CYP2E1 activity), and aminopyrine-N
      demethylase (indicator of CYP1A, 2A, 2B, 2D, and 3A activity) was shown by GEO
      both in vitro and in vivo. GEO gave an IC50 value of 30, 57.5, and 40 ug for
      CYP1A1, CYP1A2, and CYP2B1/2, respectively, 55 ug for aniline hydroxylase, and
      37.5 ug for aminopyrene-N-demethylase. GEO also significantly increased the
      levels of phase II carcinogen-metabolizing enzymes uridine 5'-diphospho
      glucuronyl transferase and glutathione-S-transferase in vivo indicating the use
      of GEO as an antimutagen and as a potential chemopreventive agent.

PMID- 24023004
TI  - Adeno-associated virus (AAV) vectors in gene therapy: immune challenges and
      strategies to circumvent them.
AB  - AAV-based gene transfer protocols have shown remarkable success when directed to
      immune-privileged sites such as for retinal disorders like Lebers congenital
      amaurosis. In contrast, AAV-mediated gene transfer into liver or muscle tissue
      for diseases such as hemophilia B, alpha1 anti-trypsin deficiency and muscular
      dystrophy has demonstrated a decline in gene transfer efficacy over time. It is
      now known that in humans, AAV triggers specific pathways that recruit immune
      sensors. These factors initiate an immediate reaction against either the viral
      capsid or the vector encoded protein as part of innate immune response or to
      produce a more specific adaptive response that generates immunological memory.
      The vector-transduced cells are then rapidly destroyed due to this immune
      activation. However, unlike other viral vectors, AAV is not immunogenic in murine
      models. Its immunogenicity becomes apparent only in large animal models and human
      subjects. Moreover, humans are natural hosts to AAV and exhibit a high
      seroprevalence against AAV vectors. This limits the widespread application of AAV
      vectors into patients with pre-existing neutralising antibodies or memory T
      cells. To address these issues, various strategies are being tested. Alternate
      serotype vectors (AAV1-10), efficient expression cassettes, specific tissue
      targeting, immune-suppression and engineered capsid variants are some approaches
      proposed to minimise this immune stimulation. In this review, we have summarised
      the nature of the immune response documented against AAV in various pre-clinical
      and clinical settings and have further discussed the strategies to evade them.

PMID- 24023005
TI  - Stabilized second-order convex splitting schemes for Cahn-Hilliard models with
      application to diffuse-interface tumor-growth models.
AB  - We present unconditionally energy-stable second-order time-accurate schemes for
      diffuse-interface (phase-field) models; in particular, we consider the Cahn
      Hilliard equation and a diffuse-interface tumor-growth system consisting of a
      reactive Cahn-Hilliard equation and a reaction-diffusion equation. The schemes
      are of the Crank-Nicolson type with a new convex-concave splitting of the free
      energy and an artificial-diffusivity stabilization. The case of nonconstant
      mobility is treated using extrapolation. For the tumor-growth system, a semi
      implicit treatment of the reactive terms and additional stabilization are
      discussed. For suitable free energies, all schemes are linear. We present
      numerical examples that verify the second-order accuracy, unconditional energy
      stability, and superiority compared with their first-order accurate variants.

PMID- 24023006
TI  - Capture-recapture estimates of the undercount of workplace injuries and
      illnesses: sensitivity analysis.
AB  - BACKGROUND: In recent years, capture-recapture methods have been applied to state
      Survey of Occupational Injuries and Illnesses (SOII) and workers' compensation
      data, but uncertainties arise because of population differences between the two
      sources, likely source dependence, and concerns about the accuracy of case
      linkage. METHODS: We linked SOII and workers' compensation records for California
      and used capture-recapture methods to estimate the proportion of injuries and
      illnesses involving at least 4 days away from work captured by each source. We
      then did a sensitivity analysis. RESULTS: Assuming source independence, estimates
      of the proportion of injuries and illnesses involving at least 4 days away from
      work captured by the SOII varied from 42.4% to 49.0%, while workers' compensation
      estimates were between 76.9% and 77.6%. Re-estimating SOII capture rates assuming
      source dependence (OR = 3) reduced capture estimates substantially. CONCLUSIONS:
      Estimated capture rates remained low after changing several of the underlying
      assumptions. Positive source dependence had the greatest impact.

PMID- 24023003
TI  - Smad1 and 5 but not Smad8 establish stem cell quiescence which is critical to
      transform the premature hair follicle during morphogenesis toward the postnatal
      state.
AB  - Hair follicles (HFs) are regenerative miniorgans that offer a highly informative
      model system to study the regulatory mechanisms of hair follicle stem cells
      (hfSCs) homeostasis and differentiation. Bone morphogenetic protein (BMP)
      signaling is key in both of these processes, governing hfSCs quiescence in the
      bulge and differentiation of matrix progenitors. However, whether canonical or
      noncanonical pathways of BMP signaling are responsible for these processes
      remains unresolved. Here, we conditionally ablated two canonical effectors of BMP
      signaling, Smad1 and Smad5 during hair morphogenesis and postnatal cycling in
      mouse skin. Deletion of Smad1 and Smad5 (dKO) in the epidermis during
      morphogenesis resulted in neonatal lethality with lack of visible whiskers.
      Interestingly, distinct patterns of phospho-Smads (pSmads) activation were
      detected with pSmad8 restricted to epidermis and pSmad1 and pSmad5 exclusively
      activated in HFs. Engraftment of dKO skin revealed retarded hair morphogenesis
      and failure to differentiate into visible hair. The formation of the prebulge and
      bulge reservoir for quiescent hfSCs was precluded in dKO HFs which remained in
      prolonged anagen. Surprisingly, in postnatal telogen HFs, pSmad8 expression was
      no longer limited to epidermis and was also present in dKO bulge hfSCs and matrix
      progenitors. Although pSmad8 activity alone could not prevent dKO hfSCs
      precocious anagen activation, it sustained efficient postnatal differentiation
      and regeneration of visible hairs. Together, our data suggest a pivotal role for
      canonical BMP signaling demonstrating distinguished nonoverlapping function of
      pSmad8 with pSmad1 and pSmad5 in hfSCs regulation and hair morphogenesis but a
      redundant role in adult hair progenitors differentiation.

PMID- 24023007
TI  - Genome wide identification and expression profile in epithelial cells exposed to
      TiO2 particles.
AB  - Environmental particles are believed to provoke airway inflammation in
      susceptible individuals by stimulating epithelial cells to release mediators that
      exacerbate lung diseases. Here, we sought to identify genes expressed throughout
      the genome by epithelial cells stimulated with TiO2 particles. A human bronchial
      epithelial cell line, BEAS-2B, was stimulated with or without 40 ug TiO2 for 2 h.
      RNA was purified from cells and subjected to microarray analysis. Genes
      exhibiting more than a twofold change in RNA expression were selected. Candidate
      genes were then analyzed using bioinformatics tools, including pathway, ontology,
      and network analyses. ITGAV mRNA expression levels were measured in BEAS-2B cells
      using real-time polymerase chain reaction. Among 37,803 genes, 92 genes displayed
      more than a twofold change in mRNA levels according to the microarray analysis;
      87 genes were upregulated while five genes were downregulated. The 92 genes were
      classified based on functional annotation using a protein information resource
      database search for biological processes and a pathway search using the KEGG
      pathway database. These genes are related to macromolecule biosynthesis,
      metabolic processes and, in particular, RNA metabolism. When genes with more than
      a threefold change were analyzed, KIF11, ITGAV, SEMA3C, IBTK, and DEK were
      selected as candidate genes induced by TiO2 -stimulated BEAS-2B cells. To
      validate these results, BEAS-2B cells stimulated with 40 ug TiO2 expressed
      threefold higher ITGAV mRNA levels compared to those without TiO2 particle
      stimulation. We conclude that KIF11, ITGAV, SEMA3C, IBTK, and DEK are candidate
      genes expressed by epithelial cells when stimulated with TiO2 particles.

PMID- 24023008
TI  - Photophysical and laser properties of cassettes based on a BODIPY and rhodamine
      pair.
AB  - This work deals with the synthesis and the photophysical and laser properties of
      new BODIPY-rhodamine cassettes. These dyads differ in their rigid and conjugated
      spacer group (phenyl or acetylenephenyl) and in their linking positions (meta or
      para). The photophysical properties of these cassettes are controlled by the
      formation/opening of the spirolactone ring, which, in turn, switches off/on an
      energy-transfer process between the chromophores. Herein, we thoroughly describe
      the influence of the attached spacer group, as well as the distance and
      orientation between the donor-acceptor pair, on the excitation energy transfer.
      The observed fast dynamics and efficiency suggest that the process mainly takes
      place "through-bond", although the "through-space" mechanism also contributes to
      the whole process. As a result, efficient laser emission from the rhodamine is
      achieved upon excitation of the BODIPY, in particular for the cassette that
      contains an acetylenephenyl spacer group in a para disposition. 

PMID- 24023009
TI  - Depressive symptoms and rheumatoid arthritis: spouse empathic responding as a
      buffer.
AB  - OBJECTIVE: To examine the effects of depressive symptoms and spouse empathic
      responding on patient disability and marital quality over time and to identify
      factors that contribute to patients perceiving their spouses as responding
      empathically to their rheumatoid arthritis (RA). METHODS: Patients diagnosed with
      RA and their spouses (n = 133 couples) independently completed mailed
      questionnaires at baseline and 1 year later. Patients completed measures of
      functional impairment, marital quality, depressive symptoms, and perceived
      empathic responding from their spouse. Spouses reported their own depressive
      symptoms and empathic responding behavior. RESULTS: Perceived empathic responding
      was found to interact with spouse depressive symptoms, contributing significantly
      to the prediction of patient functional impairment at followup. Only when spouse
      empathic responding was low was spouse depression associated with greater patient
      functional impairment 1 year later. Similarly, in the model predicting patient
      marital quality at followup, there were significant 2-way interactions between
      perceived empathic responding and both spouse depressive symptoms and patient
      depressive symptoms. Only when spouse empathic responding was low did patient or
      spouse depression significantly predict poorer marital quality at followup.
      Patient perceptions of spouse empathic responding were found to depend on spouse
      reports of their own empathic responding, patient marital satisfaction, and the
      interaction of patient depressive symptoms and marital satisfaction. CONCLUSION:
      Empathic responding from the spouse was found to buffer against the negative
      effects of spouse depression on functional and marital outcomes for patients with
      RA. In developing couple-oriented RA treatments, increasing perceived empathic
      responding could serve as a useful target for intervention.

PMID- 24023010
TI  - A novel negative regulator of adipogenesis: microRNA-363.
AB  - The differentiation of adipose tissue-derived stromal cells (ADSCs) into
      adipocytes involves a highly orchestrated series of events that includes cell
      lineage commitment, mitotic clonal expansion, growth arrest, and terminal
      differentiation. However, the molecular mechanisms controlling adipogenesis are
      not yet completely understood. In this study, we investigated whether microRNAs
      (miRNAs) play a role in adipocyte differentiation. Microarray analysis was
      performed to determine the miRNA expression profile during ADSC differentiation,
      and miR-363 was found to be one of the most significantly downregulated miRNAs.
      We show that the overexpression of miR-363 in ADSCs inhibited mitotic clonal
      expansion and terminal differentiation. Furthermore, ectopic introduction of miR
      363 into ADSCs markedly reduced the levels of E2F3, a key transcription factor
      that regulates growth and proliferation during mitotic clonal expansion. Finally,
      using an EGFP/RFP reporter assay, we demonstrate that miR-363 can directly target
      the 3'UTR of E2F3. Taken together, these results suggest that miR-363 regulates
      the transition from mitotic clonal expansion to terminal differentiation during
      adipogenesis in ADSCs, at least in part, by targeting E2F3.

PMID- 24023012
TI  - Differential activation of signaling pathways by low-osmolar and iso-osmolar
      radiocontrast agents in human renal tubular cells.
AB  - Radiocontrast media (RCM)-induced nephrotoxicity (CIN) is a major clinical
      problem accounting for 12% of all hospital-acquired cases of acute kidney injury
      (AKI). The pathophysiology of AKI due to RCM is not well understood, but direct
      toxic effects on renal cells have been postulated as contributing to CIN. It is
      believed that iso-osmolar RCM (IOCM) are less nephrotoxic than low-osmolar RCM
      (LOCM) but clinical data have been controversial. We have investigated the
      intracellular signaling pathways that may be affected by the LOCM iomeprol (IOM)
      and the IOCM iodixanol (IOD). Both IOM and IOD caused a dramatic decrease in
      phosphorylation of the kinase Akt at Ser473 and Thr308 in human renal tubular (HK
      2) cells, with IOM having a greater effect; IOM also caused a greater decrease in
      cell viability. IOM also had a greater effect on phosphorylation of p38 MAP
      kinases, JNKs, and NF-kB (Ser276), and caused a marked decrease in the
      phosphorylation of forkhead box O3a (FOXO3a) and signal transducer and activator
      of transcription 3 (STAT3). However, IOD caused a greater decrease in the
      phosphorylation of mTOR (Ser2448) and phospho-ERK 1/2 while both RCM caused a
      similar decrease in the phosphorylation of phospho-p70S6 kinase (Ser371). In vivo
      studies showed that both IOM and IOD caused a significant decrease in both pAkt
      (Ser473) and pERK 1/2 in rat kidneys. Our study gives an insight into the
      possible mechanism of toxicity of RCM via their action on intracellular signaling
      pathways and may help in developing pharmacological interventions for their side
      effects.

PMID- 24023011
TI  - Potential of computer-aided diagnosis of high spectral and spatial resolution
      (HiSS) MRI in the classification of breast lesions.
AB  - PURPOSE: To compare the performance of computer-aided diagnosis (CADx) analysis
      of precontrast high spectral and spatial resolution (HiSS) MRI to that of
      clinical dynamic contrast-enhanced MRI (DCE-MRI) in the diagnostic classification
      of breast lesions. MATERIALS AND METHODS: Thirty-four malignant and seven benign
      lesions were scanned using two-dimensional (2D) HiSS and clinical 4D DCE-MRI
      protocols. Lesions were automatically segmented. Morphological features were
      calculated for HiSS, whereas both morphological and kinetic features were
      calculated for DCE-MRI. After stepwise feature selection, Bayesian artificial
      neural networks merged selected features, and receiver operating characteristic
      (ROC) analysis evaluated the performance with leave-one-lesion-out validation.
      RESULTS: AUC (area under the ROC curve) values of 0.92 +/- 0.06 and 0.90 +/- 0.05
      were obtained using CADx on HiSS and DCE-MRI, respectively, in the task of
      classifying benign and malignant lesions. While we failed to show that the higher
      HiSS performance was significantly better than DCE-MRI, noninferiority testing
      confirmed that HiSS was not worse than DCE-MRI. CONCLUSION: CADx of HiSS (without
      contrast) performed similarly to CADx on clinical DCE-MRI; thus, computerized
      analysis of HiSS may provide sufficient information for diagnostic
      classification. The results are clinically important for patients in whom
      contrast agent is contra-indicated. Even in the limited acquisition mode of 2D
      single slice HiSS, by using quantitative image analysis to extract
      characteristics from the HiSS images, similar performance levels were obtained as
      compared with those from current clinical 4D DCE-MRI. As HiSS acquisitions become
      possible in 3D, CADx methods can also be applied. Because HiSS and DCE-MRI are
      based on different contrast mechanisms, the use of the two protocols in
      combination may increase diagnostic accuracy.

PMID- 24023013
TI  - Extensive proteomic remodeling is induced by eukaryotic translation elongation
      factor 1Bgamma deletion in Aspergillus fumigatus.
AB  - The opportunistic pathogen Aspergillus fumigatus is ubiquitous in the environment
      and predominantly infects immunocompromised patients. The functions of many genes
      remain unknown despite sequencing of the fungal genome. A putative translation
      elongation factor 1Bgamma (eEF1Bgamma, termed elfA; 750 bp) is expressed, and
      exhibits glutathione S-transferase activity, in A. fumigatus. Here, we
      demonstrate the role of ElfA in the oxidative stress response, as well as a
      possible involvement in translation and actin cytoskeleton organization,
      respectively. Comparative proteomics, in addition to phenotypic analysis, under
      basal and oxidative stress conditions, demonstrated a role for A. fumigatus elfA
      in the oxidative stress response. An elfA-deficient strain (A. fumigatus
      DeltaelfA) was significantly more sensitive to the oxidants H2O2, diamide, and
      4,4'-dipyridyl disulfide (DPS) than the wild-type. This was further supported
      with the identification of differentially expressed proteins of the oxidative
      stress response, including; mitochondrial peroxiredoxin Prx1, molecular chaperone
      Hsp70 and mitochondrial glycerol-3-phosphate dehydrogenase. Phenotypic analysis
      also revealed that A. fumigatus DeltaelfA was significantly more tolerant to
      voriconazole than the wild-type. The differential expression of two aminoacyl
      tRNA synthetases suggests a role for A. fumigatus elfA in translation, while the
      identification of actin-bundling protein Sac6 and vacuolar dynamin-like GTPase
      VpsA link A. fumigatus elfA to the actin cytoskeleton. Overall, this work
      highlights the diverse roles of A. fumigatus elfA, with respect to translation,
      oxidative stress and actin cytoskeleton organization. In addition to this, the
      strategy of combining targeted gene deletion with comparative proteomics for
      elucidating the role of proteins of unknown function is further revealed.

PMID- 24023015
TI  - The effective concentration of tranexamic acid for inhibition of fibrinolysis in
      neonatal plasma in vitro.
AB  - BACKGROUND: Neonates are at high risk for bleeding complications after
      cardiovascular surgery. Activation of intravascular fibrinolysis is one of the
      principal effects of cardiopulmonary bypass that causes poor postoperative
      hemostasis. Antifibrinolytic medications such as tranexamic acid are often used
      as prophylaxis against fibrinolysis, but concentration/effect data to guide
      dosing are sparse for adults and have not been published for neonates. Higher
      concentrations of tranexamic acid than those necessary for inhibition of
      fibrinolysis may have adverse effects. Therefore, we investigated the
      concentration of tranexamic acid necessary to inhibit activated fibrinolysis in
      neonatal plasma. METHODS: We conducted an in vitro study using neonatal plasma
      derived from the placenta/cord units from 20 term, elective cesarean deliveries.
      Graded concentrations of tranexamic acid were added to aliquots of the pooled
      plasma before maximally activating fibrinolysis with high-dose tissue-type
      plasminogen activator. Thromboelastography was then performed with the primary
      outcome variable being lysis at 30 minutes. These procedures were repeated on
      pooled adult normal plasma and dilutions of neonatal plasma. RESULTS: The minimum
      concentrations of tranexamic acid to completely prevent fibrinolysis were 6.54
      MUg/mL (95% confidence interval, 5.19-7.91) for neonatal plasma and 17.5 MUg/mL
      (95% confidence interval, 14.59-20.41) for adult plasma. Neonatal plasma requires
      a significantly lower concentration than adult plasma (P < 0.0001, 2-sided Wald
      test). CONCLUSIONS: Our data establish the minimal effective concentration of
      tranexamic acid necessary to completely prevent fibrinolysis in neonatal plasma
      in vitro. These data may be useful in designing a dosing scheme for tranexamic
      acid appropriate for neonates.

PMID- 24023014
TI  - The effect of dipeptidyl peptidase-IV inhibition on bone in a mouse model of type
      2 diabetes.
AB  - BACKGROUND: Individuals with type 2 diabetes (T2D) are at greater risk of bone
      fractures than those without diabetes. Certain oral diabetic medications may
      further increase the risk of fracture. Dipeptidyl peptidase-IV (DPP-IV)
      inhibitors are incretin-based therapies that are being increasingly used for the
      management of T2D. It has been hypothesized that these agents may reduce fracture
      risk in those with T2D. In this study, we used a mouse model of T2D to examine
      the effects of the DPP-IV inhibitor, MK-0626, on bone. METHODS: Male wild type
      (WT) and diabetic muscle-lysine-arginine (MKR) mice were treated with MK-0626,
      pioglitazone, alendronate or vehicle. The effects of treatment with MK-0626 on
      bone microarchitecture and turnover were compared with treatment with
      pioglitazone, alendronate and vehicle. Osteoblast differentiation was determined
      by alkaline phosphatase staining of bone marrow cells from WT and MKR mice after
      treatment with pioglitazone, MK-0626 or phosphate buffered saline. RESULTS: We
      found that MK-0626 had neutral effects on cortical and trabecular bone in
      diabetic mice. Pioglitazone had detrimental effects on the trabecular bone of WT
      but not of diabetic mice. Alendronate caused improvements in cortical and
      trabecular bone architecture in diabetic and WT mice. MK-0626 did not alter
      osteoblast differentiation, but pioglitazone impaired osteoblast differentiation
      in vitro. CONCLUSIONS: Overall, the DPP-IV inhibitor, MK-0626, had no adverse
      effects on bone in an animal model of T2D or directly on osteoblasts in culture.
      These findings are reassuring as DPP-IV inhibitors are being widely used to treat
      patients with T2D who are already at an increased risk of fractures.

PMID- 24023016
TI  - Sevoflurane end-tidal to effect-site equilibration in women determined by
      response to laryngeal mask airway insertion.
AB  - BACKGROUND: End-tidal concentrations (CET) have been used to guide delivery of
      inhaled anesthetic drugs for many years. Effect-site concentrations (Ceff) are a
      frequently used guide to therapy with IV drugs and should also be of benefit with
      inhaled drugs, especially during periods of rapid change. For Ceff to be useful,
      the appropriate levels required for any given end point, and the delay between
      central compartment and effect, need to be defined. In this study, we explored
      these relationships for the effect of response to insertion of the classic
      laryngeal mask airway (cLMA) and compared the utility of CET and Ceff-guided cLMA
      insertion. METHOD: We studied 30 ASA physical status I or II patients in whom
      induction with sevoflurane alone and use of the cLMA were appropriate. After
      oxygen administration from a circle system with a total gas flow of 6 L/min, the
      sevoflurane vaporizer dial was set to 6%. cLMA insertion was attempted at a
      predetermined Ceff calculated in real time based on measured CET. Target levels
      were chosen using up-and-down methodology. The initial value was 2.5 vol% with a
      step size of 0.2 vol%. Subjects showing a gross motor response were responders,
      and the target was increased for the next subject. Those without such a response
      were nonresponders, and the target was decreased for the next subject. Data
      collection continued until after 7 transitions from nonresponder to responder.
      For each subject, after the first transition, we calculated a Ceff time series
      from the measured CET time series for 11 t(1/2)ke0 values between 0.5 and 5.0
      minutes. We combined data from 2 studies of equilibrium 50% effective
      concentration (EC50) for LMA insertion to derive a pooled EC50 of 2.17%. We
      determined graphically the t(1/2)ke0 that gave a mean EC50 of 2.17% in our
      subjects. We constructed receiver operator characteristic curves to compare the
      utility of CET and Ceff-guided cLMA insertion. RESULTS: The 30 patients studied
      were all women, ASA physical status I or II, aged between 22 and 66 years (mean
      38). Consciousness was lost after 99.2 (SD 11.1) seconds, and the target for cLMA
      insertion reached after 256 (57) seconds. The optimum t(1/2)ke0 was 2.25 minutes
      (95% confidence interval, 2.0-2.5 minutes). The area under the receiver operator
      characteristic curves was significantly different at 0.87 (SE 0.06) for Ceff and
      0.63 (0.11) for CET. CONCLUSIONS: This study confirmed that real-time calculation
      and display of Ceff based on measured CET values are feasible. We determined the
      optimum t(1/2)ke0 for sevoflurane for the effect of cLMA insertion as 2.25
      minutes, similar to that determined for loss of consciousness using the raw
      electroencephalogram. We also showed that Ceff is a more reliable (P < 0.05)
      guide to successful cLMA insertion than CET.

PMID- 24023018
TI  - A rare case of mitral stenosis after MitraClip placement: transesophageal
      echocardiography findings and examination.

PMID- 24023017
TI  - The association between perioperative hemoglobin and acute kidney injury in
      patients having noncardiac surgery.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication of noncardiac
      surgery and is associated with excess morbidity and mortality. Perioperative
      hemoglobin concentrations are strongly associated with surgical mortality, but
      little is known about their relationship with AKI. We studied hemoglobin
      concentration before and 24 hours after surgery and its association with AKI.
      METHODS: We performed a single-center observational cohort study using clinical
      and administrative data from the Cleveland Clinic, Cleveland, OH. In patients
      with normal preoperative renal function, we examined the association between the
      outcome of AKI and the exposures of preoperative hemoglobin concentration and
      decrements in hemoglobin concentration in the first 24 hours after surgery using
      logistic regression and controlling for important confounding variables. RESULTS:
      We included 27,381 patients who had 33,330 noncardiac surgeries. AKI developed in
      2478 (7.4%) surgeries. Preoperative hemoglobin concentrations were <12.0 g/dL in
      9566 (29%) patients. Hemoglobin concentrations decreased by >4.0 g/dL in 10,808
      (32%) patients. Compared with patients with a preoperative hemoglobin >12.0 g/dL,
      the adjusted odds ratio (OR) for AKI was 2.01 (95% confidence interval [CI], 1.8
      2.3) for those with a preoperative hemoglobin between 10.1 and 12.0 g/dL and was
      3.7 (95% CI, 2.6-5.4) for those with a preoperative hemoglobin <8.0 g/dL.
      Compared with patients who did not have a decrease in postoperative hemoglobin, a
      decrement of 1.1 to 2.0 g/dL was associated with an adjusted OR of 1.51 (95% CI,
      1.15-1.98), and a decrement of >4.0 g/dL with an OR of 4.7 (95% CI, 3.6-6.2) for
      AKI. CONCLUSIONS: Low preoperative and early postoperative decrements in
      hemoglobin concentrations are strongly associated with postoperative AKI in a
      graded manner. Given the frequency of low perioperative hemoglobin and decreases
      in hemoglobin concentration, research is needed to determine whether there are
      safe treatment strategies to mitigate the risk of AKI.

PMID- 24023019
TI  - Rescheduling of previously cancelled surgical cases does not increase variability
      in operating room workload when cases are scheduled based on maximizing
      efficiency of use of operating room time.
AB  - BACKGROUND: Conceptually, cancelling a case close to the scheduled day of surgery
      increases variability in operating room (OR) workload (i.e., total hours of
      scheduled cases plus turnovers), creating managerial problems. However, in our
      recent study of an OR scheduling office, cancellations (slightly) reduced
      variability in workload among days. If a relatively low incidence of
      cancellations does not cause increased variability in workload, this would be a
      useful finding when focusing strategic OR management initiatives. However, the
      previous study considered only the effect on the schedule for the day the
      cancelled case originally was scheduled to be performed, not the future date on
      which the case was performed. METHODS: For 90% of cancelled cases, the patient
      later underwent the same or a similar procedure at the studied hospital. Thus,
      the OR schedule at 7:00 am each day over 2 years could be used to study case
      rescheduling. The primary end point, calculated for each surgeon, was the
      difference of 2 ratios. The first ratio was the proportion of scheduled workload
      attributable to previously cancelled cases, among all days for which the
      surgeon's workload exceeded the surgeon's median workload. The second ratio was
      that proportion among the other days when the surgeon performed at least 1 case.
      Means +/- SEMs were calculated by random effects analysis, stratified by surgeon.
      RESULTS: From 7:00 am the working day before surgery through the day of surgery,
      9.7% +/- 0.6% of scheduled OR hours and 9.7% +/- 0.5% of cases were cancelled.
      Among cases performed, 9.5% +/- 0.5% of the scheduled hours and 9.5% +/- 0.5% of
      the cases were previously cancelled (i.e., rescheduled to a later date and then
      performed). Surgeons' median workloads on days with at least 1 case were 8.3 +/-
      0.2 hours. The percentage of scheduled workload attributable to rescheduled cases
      was slightly less on days when the surgeon had larger than median workloads (
      0.7% +/- 0.3%, P = 0.022). CONCLUSIONS: Rescheduled cancelled cases did not
      increase variability in OR workload. This finding is useful combined with our
      recent finding that cancellation slightly reduces variability in OR workload on
      the date of cancellation. Cancellations should not be interpreted as a system
      failure that increases variability in surgical workload. We recommend that
      anesthesiologists aim to reduce cancellation rates if above benchmarked averages,
      but otherwise focus on more strategically beneficial initiatives. We recommend
      also that these results be considered if cancellation rates are used in assessing
      anesthesiology group performance.

PMID- 24023020
TI  - Maternal sepsis mortality and morbidity during hospitalization for delivery:
      temporal trends and independent associations for severe sepsis.
AB  - BACKGROUND: Sepsis is currently the leading cause of direct maternal death in the
      United Kingdom. In this study, we aimed to determine frequency, temporal trends,
      and independent associations for severe sepsis during hospitalization for
      delivery in the United States. METHODS: Data were obtained from the Nationwide
      Inpatient Sample for the years 1998 through 2008. The presence of severe sepsis
      was identified by the appropriate International Classification of Diseases, Ninth
      Revision, Clinical Modification codes. Logistic regression analysis was used to
      assess temporal trends for sepsis, severe sepsis, and sepsis-related death and
      also to identify independent associations of severe sepsis. RESULTS: Of an
      estimated 44,999,260 hospitalizations for delivery, sepsis complicated 1:3333
      (95% confidence interval [CI], 1:3151-1:3540) deliveries, severe sepsis
      complicated 1:10,823 (95% CI, 1:10,000-1:11,792) deliveries, and sepsis-related
      death complicated 1:105,263 (95% CI, 1:83,333-1:131,579) deliveries. While the
      overall frequency of sepsis was stable(P = 0.95), the risk of severe sepsis and
      sepsis-related death increased during the study period, (P < 0.001) and (P =
      0.02), respectively. Independent associations for severe sepsis, with an adjusted
      odds ratio and lower bound 95% CI higher than 3, include congestive heart
      failure, chronic liver disease, chronic renal disease, systemic lupus
      erythematous, and rescue cerclage placement. CONCLUSIONS: Maternal severe sepsis
      and sepsis-related deaths are increasing in the United States. Severe sepsis
      often occurs in the absence of a recognized risk factor and underscores the need
      for developing systems of care that increase sensitivity for disease detection
      across the entire population. Physicians should enhance surveillance in patients
      with congestive heart failure, chronic liver disease, chronic renal disease, and
      systemic lupus erythematous and institute early treatment when signs of sepsis
      are emerging.

PMID- 24023021
TI  - Statistical grand rounds: understanding the mechanism: mediation analysis in
      randomized and nonrandomized studies.
AB  - In comparative clinical studies, a common goal is to assess whether an exposure,
      or intervention, affects the outcome of interest. However, just as important is
      to understand the mechanism(s) for how the intervention affects outcome. For
      example, if preoperative anemia was shown to increase the risk of postoperative
      complications by 15%, it would be important to quantify how much of that effect
      was due to patients receiving intraoperative transfusions. Mediation analysis
      attempts to quantify how much, if any, of the effect of an intervention on
      outcome goes though prespecified mediator, or "mechanism" variable(s), that is,
      variables sitting on the causal pathway between exposure and outcome. Effects of
      an exposure on outcome can thus be divided into direct and indirect, or mediated,
      effects. Mediation is claimed when 2 conditions are true: the exposure affects
      the mediator and the mediator (adjusting for the exposure) affects the outcome.
      Understanding how an intervention affects outcome can validate or invalidate
      one's original hypothesis and also facilitate further research to modify the
      responsible factors, and thus improve patient outcome. We discuss the proper
      design and analysis of studies investigating mediation, including the importance
      of distinguishing mediator variables from confounding variables, the challenge of
      identifying potential mediators when the exposure is chronic versus acute, and
      the requirements for claiming mediation. Simple designs are considered, as well
      as those containing multiple mediators, multiple outcomes, and mixed data types.
      Methods are illustrated with data collected by the National Surgical Quality
      Improvement Project (NSQIP) and utilized in a companion paper which assessed the
      effects of preoperative anemic status on postoperative outcomes. 

PMID- 24023022
TI  - The influence of spinal flexion in the lateral decubitus position on the
      unilaterality of spinal anesthesia.
AB  - BACKGROUND: For unilateral spinal block, local anesthetics should affect the
      spinal nerves of 1 side. With full flexion of the spine, the sunken cauda equina
      becomes tightened and is suspended in the middle of the subarachnoid space. We
      performed this study to assess whether spinal flexion facilitates unilateral
      spinal anesthesia. METHODS: Hyperbaric bupivacaine (8 mg) was administered at the
      L3-4 interspace through a 25-gauge Quincke needle at a rate of 0.02 mL/s.
      Patients were randomly allocated to group F (with full spinal flexion) or group N
      (the hips and back straightened). After maintaining the lateral position for 15
      minutes with or without spinal flexion, patients were gently returned to the
      supine position. Spinal blockade was assessed by loss of pinprick sensation and
      the modified Bromage motor scale. RESULTS: While the lateral position was
      maintained, sensory block was noted on the nondependent side in 14 of 16 patients
      in group N (87.5%) but only in 1 of 16 patients in group F (6.3%) (P < 0.001).
      The median level of sensory block in group N was L5 on the nondependent side just
      before turning to the supine position. When patients were returned to the supine
      position, sensory blockade on the nondependent side was noted in all group N
      patients (100%) and 15 group F patients (93.7%). The sensory level on the
      nondependent side between group N and group F were similar after turning supine.
      CONCLUSIONS: Strict unilateral sensory block was not achieved even after lateral
      decubitus positioning with spinal flexion, when 8 mg hyperbaric bupivacaine was
      administered manually at a conventionally slow rate through a beveled spinal
      needle. However, maintaining flexion of the spinal column during lateral
      decubitus positioning altered the initial onset of sensory block with respect to
      laterality.

PMID- 24023023
TI  - Pediatric perioperative life support.
AB  - Pediatric advanced life support training and guidelines are typically designed
      for first-responders and out-of-hospital resuscitation. Guidelines and scenarios
      that are more applicable to the perioperative environment would be beneficial for
      anesthesiologists. The goal of this article is to review resuscitation of
      pediatric patients during the perioperative period. We use a format that focuses
      on preresuscitation preparation, resuscitation techniques, and postresuscitation
      management in the perioperative period. In an effort to provide information of
      maximum benefit to anesthesiologists, we include common pediatric perioperative
      arrest scenarios with detailed description of their management. We also provide a
      section on postresuscitation management and review the techniques for maintaining
      the child's hemodynamic and metabolic stability. Finally, 3 appendices are
      included: an example of an intraoperative arrest record that provides feedback
      for interventions; a table of key medications for pediatric perioperative
      resuscitation; and a review of defibrillator use and simulation exercises to
      promote effective defibrillation. 

PMID- 24023024
TI  - Neuraxial anesthesia decreases postoperative systemic infection risk compared
      with general anesthesia in knee arthroplasty.
AB  - BACKGROUND: Surgical stress has been shown to result in immune disturbance.
      Neuraxial anesthesia (NA) has long been hypothesized to blunt undesired surgical
      insults and thus limit immune compromise and improve surgical outcomes. We
      hypothesized that NA would decrease postoperative infectious complications
      compared with general anesthesia (GA) among knee arthroplasty patients. METHODS:
      We studied the American College of Surgeons National Surgical Quality Improvement
      Program database from 2005 to 2010. There were 16,555 patients included in our
      final cohort, with 9167 patients receiving GA and 7388 patients receiving spinal
      or epidural anesthesia.. Outcomes of interest included infection-related 30-day
      postoperative complications, including surgical site-related infections,
      pneumonia, urinary tract infection, sepsis, septic shock, and a composite end
      point of any systemic infection. Multivariable logistic regression was performed
      to test for effect of anesthesia type while adjusting for the influence of
      preexisting comorbidities. RESULTS: The overall mortality was 0.24% and 0.15%
      among NA and GA subjects, respectively (P = 0.214). NA subjects had fewer
      unadjusted incidences of pneumonia (P = 0.035) and composite systemic infection
      (P = 0.006). After risk adjustment for preexisting comorbidities, NA was
      associated with lower odds of pneumonia (odds ratio = 0.51 [95% confidence
      interval, 0.29-0.90]) and lower odds of composite systemic infection (odds ratio
      = 0.77 [95% confidence interval, 0.64-0.92]). CONCLUSIONS: Our study suggested
      that NA was associated with lower adjusted odds of both pneumonia and a composite
      outcome of any systemic infectious complication within 30 days of surgery
      compared with GA.

PMID- 24023025
TI  - Direct pulse oximetry within the esophagus, on the surface of abdominal viscera,
      and on free flaps.
AB  - BACKGROUND: Pulse oximetry is a noninvasive photometric technique that provides
      information about arterial blood oxygen saturation (SpO2) and heart rate and has
      widespread clinical applications. This is accomplished via peripheral pulse
      oximetry probes mainly attached to the finger, toe, or earlobe. The direct
      application of pulse oximetry to an organ, such as the esophagus, liver, bowel,
      stomach or free flap, might provide an indication of how well perfused an organ
      or a free flap is. Also, the placement of a pulse oximetry probe at a more
      central site, such as the esophagus, might be more reliable at a time when
      conventional peripheral pulse oximetry fails. METHODS: The focus of this article
      is the development and in vivo applications of new custom-made
      photoplethysmographic (PPG) and pulse oximetry optical and fiberoptic probes and
      instrumentation in an effort to investigate their suitability for the estimation
      of arterial blood oxygen saturation at different organs and tissues. The article
      will cover examples of application areas including real-time PPG and SpO2
      monitoring for the esophagus and solid organs, including free flaps, using custom
      made probes. RESULTS: Clinical studies have successfully demonstrated the
      feasibility of acquiring PPGs and estimating arterial blood oxygen saturation
      values from a variety of organs and tissues. CONCLUSIONS: The technological
      developments and the measurements presented in this work pave the way to a new
      era of pulse oximetry where direct and continuous monitoring of blood oxygen
      saturation of internal organs and tissues (esophagus, bowel, liver, stomach, free
      flaps) could be possible.

PMID- 24023026
TI  - Universal access to essential vital signs monitoring.
AB  - Much more than a telephone, today's mobile device has become an integral part of
      the way we interface with the world. Mobile devices have the computing
      capability, display, and battery power to become powerful medical devices that
      measure vital signs and provide intelligent interpretation or immediate
      transmission of information. The widespread adoption of mobile devices, even in
      low-resource settings, promises to make vital signs monitoring available anywhere
      and at low cost. This readily available computing power will also extend the
      utility of vital signs monitoring to new clinical indications, especially with
      the use of additional processing and integration of information. This review will
      focus on the universal promotion of pulse oximetry and advanced processing of
      plethysmography to assess variables such as respiratory rate, capillary refill
      time, and fluid responsiveness, and how these measurements may assist with
      perioperative monitoring, diagnosis, and management of pneumonia in children and
      preeclampsia in pregnancy when combined with mobile devices. 

PMID- 24023027
TI  - Factors affecting the performance of 5 cerebral oximeters during hypoxia in
      healthy volunteers.
AB  - BACKGROUND: Cerebral oximetry is a noninvasive optical technology that measures
      frontal cortex blood hemoglobin-oxygen saturation. Commercially available
      cerebral oximeters have not been evaluated independently. Unlike pulse oximeters,
      there are currently no Food and Drug Administration standards for performance or
      accuracy. We tested the hypothesis that cerebral oximeters accurately measure a
      fixed ratio of the oxygen saturation in cerebral mixed venous and arterial blood.
      METHODS: We evaluated the performance of 5 commercially available cerebral
      oximeters: the EQUANOX(r) 7600 in 3- and 4-wavelength versions (Nonin Medical,
      Plymouth, MN), FORE-SIGHT(r) (Casmed, Branford, CT), INVOS(r) 5100C (Covidien,
      Boulder, CO), and the NIRO-200NX(r) (Hamamatsu Photonics, Hamamatsu City, Japan)
      during stable isocapnic hypoxia in volunteers. Twenty-three healthy adults (14
      men, 9 women) had sensors placed on each side of the forehead. The subject's
      inspired oxygen (FIO2) was then changed to produce 6 steady-state arterial oxygen
      saturation (SaO2) levels between 100% and 70%, while end-tidal CO2 was maintained
      constant. At each plateau, simultaneous blood samples from the jugular bulb and
      radial artery were analyzed with a hemoximeter (OSM-3, Radiometer Medical A/S,
      Copenhagen, Denmark). Each cerebral oximeter's bias was calculated as the
      difference between the instrument's reading (cerebral saturation, ScO2) with the
      weighted saturation of venous and arterial blood (Sa/vO2), as specified by each
      manufacturer (INVOS: 25% arterial/75% venous; FORE-SIGHT, EQUANOX, and NIRO: 30%
      arterial/70% venous). RESULTS: Five hundred forty-two comparisons between paired
      blood samples and oximeter readings were analyzed. The pooled root mean square
      error was 8.06%, a value higher than for pulse oximeters, which is +/-3% by Food
      and Drug Administration standards. The mean % bias +/- SD (precision) and root
      mean square errors were: FORE-SIGHT 1.76 +/- 3.92 and 4.28; INVOS 0.05 +/- 9.72
      and 9.69; NIRO-200NX -1.13 +/- 9.64 and 9.68; EQUANOX-3 lambda 2.48 +/- 8.12 and
      8.47; EQUANOX-4 lambda 2.84 +/- 6.27 and 6.86. The FORE-SIGHT, NIRO-200NX, and
      EQUANOX-3 lambda had significantly more positive bias at lower SaO2. The amount
      of bias during hypoxia was reduced when the bias was calculated on the basis of
      difference between oximeter reading and the arterial and mixed venous saturation
      difference rather than the weighted average of blood saturation, indicating that
      differences in the ratio between arterial and venous blood volumes account for
      some of the positive bias at low saturation. Dark skin pigment tended to produce
      more negative bias in all instruments but bias was significantly larger than zero
      only for the FORE-SIGHT oximeter. Bias was significantly more negative in women
      for INVOS and EQUANOX devices but not for the FORE-SIGHT device. CONCLUSIONS:
      While responsive to desaturation, cerebral oximeters exhibited large variation in
      reading errors between subjects, with mean bias possibly related to variations in
      the ratio of arterial and venous blood in the sampling area of the brain. This
      ratio is probably not fixed, as assumed by the manufacturers, but dynamically
      changes with hypoxia. Better understanding these factors could improve the
      performance of cerebral oximeters and help establish saturation or blood flow
      thresholds for brain well-being.

PMID- 24023028
TI  - Effect of the substitution pattern on the intramolecular charge-transfer
      emissions in organoboron-based biphenyls, diphenylacetylenes, and stilbenes.
AB  - Three series of organoboron-based molecules, including biphenyls 1a-c,
      diphenylacetylenes 2a-c, and stilbenes 3a-c, in which the electron-accepting
      boryl and the electron-donating amino groups are introduced at different
      positions, have been comprehensively investigated to explore the effect of the
      substitution pattern on the intramolecular charge-transfer emissions. In
      cyclohexane solution, the change of substitution pattern from p,p' to o,p' by
      introduction of boryl at the lateral o-position rather than the terminal p
      position leads to bathochromism in the absorption and emission spectra. With
      further variation of the amino position from the terminal p'-position in o,p'
      substitution to the lateral o'-position in an o,o'-substitution pattern, a
      blueshift was observed in the absorption owing to the less-efficient conjugation
      extension of the amino group as the result of sp(3) hybridization. It is notable
      that the emission of the three series of molecules changes with completely
      different trends. Only the emission of the biphenyl is redshifted further from
      o,p'-substituted 1b to o,o'-substituted 1a, whereas o,o'-substituted
      diphenylacetylene 2a maintains almost the same spectrum as that of o,p'
      substituted diphenylacetylene 2b and the fluorescence of o,o'-substituted
      stilbene 3a is even blueshifted compared with o,p'-substituted stilbene 3b. As a
      result, the o,o'-substituted biphenyl 1a shows the longest emission wavelength
      despite the limited conjugation of the parent biphenyl skeleton. The long
      emission wavelength of 1a may arise from its extremely twisted structure, which
      would cause a significant structural relaxation in the exited state. In the solid
      state, 1a still keeps almost the longest emission wavelength. In addition, its
      quantum yield is also among the highest. The unusual properties, intense solid
      state emission together with long emission wavelength, and particularly large
      Stokes shift, which are difficult to attain by structural modification of other
      parent pi-conjugated frameworks, have been achieved by the introduction of boryl
      and amino groups at the o,o'-positions of the biphenyl skeleton.

PMID- 24023029
TI  - Psychometric properties of the foot and ankle outcome score in a community-based
      study of adults with and without osteoarthritis.
AB  - OBJECTIVE: Foot and ankle problems are common in adults, and large observational
      studies are needed to advance our understanding of the etiology and impact of
      these conditions. Valid and reliable measures of foot and ankle symptoms and
      physical function are necessary for this research. This study examined
      psychometric properties of the Foot and Ankle Outcome Score (FAOS) subscales
      (pain, other symptoms, activities of daily living [ADL], sport and recreational
      function [sport/recreation], and foot- and ankle-related quality of life [QOL])
      in a large, community-based sample of African American and white men and women
      ages >=50 years. METHODS: Johnston County Osteoarthritis Project participants (n
      = 1,670) completed the 42-item FAOS (mean age 69 years, 68% women, 31% African
      American, mean body mass index [BMI] 31.5 kg/m(2) ). Internal consistency, test
      retest reliability, convergent validity, and structural validity of each subscale
      were examined for the sample and for subgroups according to race, sex, age, BMI,
      presence of knee or hip osteoarthritis, and presence of knee, hip, or low back
      symptoms. RESULTS: For the sample and each subgroup, Cronbach's alpha
      coefficients ranged from 0.95-0.97 (pain), 0.97-0.98 (ADL), 0.94-0.96
      (sport/recreation), 0.89-0.92 (QOL), and 0.72-0.82 (symptoms). Correlation
      coefficients ranged from 0.24-0.52 for pain and symptoms subscales with foot and
      ankle symptoms and from 0.30-0.55 for ADL and sport/recreation subscales with the
      Western Ontario and McMaster Universities Osteoarthritis Index function subscale.
      Intraclass correlation coefficients for test-retest reliability ranged from 0.63
      0.81. Items loaded on a single factor for each subscale except symptoms (2
      factors). CONCLUSION: The FAOS exhibited sufficient reliability and validity in
      this large cohort study.

PMID- 24023030
TI  - A clinical and pathologic comparison between stage-matched endometrial
      intraepithelial carcinoma and uterine serous carcinoma: is there a difference?
AB  - Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of
      uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic
      pathologic outcomes in patients with EIC and USC for disease limited to the
      endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically
      staged patients were retrospectively identified and relevant variables were
      extracted and compared. Kaplan-Meier was used to generate the survival data. More
      USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed
      higher levels of estrogen receptor-alpha than EIC (P = .0009 and .063 for stages
      1 and 4, respectively). The survival is comparable, with 1 recurrence in each
      group for stage 1A disease. For stage 4 EIC and USC, the progression-free
      survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to
      what is previously published. In conclusion, EIC, whether limited to the
      endometrium, or widely metastatic, imparts similar outcomes and should be treated
      comparably with stage-matched USC. 

PMID- 24023032
TI  - Human epididymis protein 4 and secretory leukocyte protease inhibitor in vaginal
      fluid: relation to vaginal components and bacterial composition.
AB  - Human epididymis protein 4 (HE4) is a protease inhibitor and a recently
      identified serum biomarker for ovarian cancer. Properties of HE4 in the genital
      tract of healthy women have not been evaluated. We evaluated associations between
      HE4 and a second vaginal protease inhibitor, secretory leukocyte protease
      inhibitor (SLPI), with vaginal concentrations of innate immune mediators or
      proteases and with the types of vaginal bacterial communities. Vaginal secretions
      were collected from 18 healthy reproductive age women and assayed by enzyme
      linked immunosorbent assay for concentrations of HE4, SLPI, kallikrein 5,
      cathepsin B, interleukin 1beta (IL-1), IL-1 receptor antagonist (IL-1 ra),
      mannose-binding lectin (MBL), the inducible 70-kDa heat shock protein, and matrix
      metalloproteinase (MMP)-8. The species composition of vaginal bacterial
      communities in 16 women was characterized by sequencing amplicons derived from
      16S bacterial ribosomal RNA genes. Correlations between any 2 assays were
      analyzed by the Spearman rank correlation tests. Differences in the
      concentrations of HE4 and SLPI, and between soluble components and vaginal
      community types, were analyzed by the Mann-Whitney U tests. Vaginal HE4
      concentrations, but not SLPI levels, were positively correlated with levels of IL
      1beta (P = .0152), IL-1ra (P = .0061), MBL (P = .0100), and MMP-8 (P = .0315).
      The median vaginal HE4 level, as well as concentrations of MBL, IL-1beta, IL-1ra,
      and MMP-8, was highest when Gardnerella vaginalis dominated a vaginal community.
      The association between HE4, elevated levels of proteases, immune mediators and
      high proportions of G vaginalis strongly suggests that HE4 is a component of the
      proinflammatory immune response in the female genital tract. 

PMID- 24023031
TI  - Metyrapone blocks maternal food restriction-induced changes in female rat
      offspring lung development.
AB  - Maternal food restriction (MFR) during pregnancy affects pulmonary surfactant
      production in the intrauterine growth-restricted (IUGR) offspring through unknown
      mechanisms. Since pulmonary surfactant production is regulated by maternal and
      fetal corticosteroid levels, both known to be increased in IUGR pregnancies, we
      hypothesized that metyrapone (MTP), a glucocorticoid synthesis inhibitor, would
      block the effects of MFR on surfactant production in the offspring. Three groups
      of pregnant rat dams were used (1) control dams fed ad libitum; (2) MFR (50%
      reduction in calories) from days 10 to 22 of gestation; and (3) MFR + MTP in
      drinking water (0.5 mg/mL), days 11 to 22 of gestation. At 5 months, the MFR
      offspring weighed significantly more, had reduced alveolar number, increased
      septal thickness, and decreased surfactant protein and phospholipid synthesis.
      These MFR-induced effects were normalized by the antiglucocorticoid MTP,
      suggesting that the stress of MFR causes hypercorticoidism, altering lung
      structure and function in adulthood. 

PMID- 24023033
TI  - Bone morphogenetic protein 7 increased vascular endothelial growth factor (VEGF)
      a expression in human granulosa cells and VEGF receptor expression in endothelial
      cells.
AB  - The formation of an individual capillary network in the theca cell layer is
      required for ovarian folliculogenesis. Although vascular endothelial growth
      factor (VEGF) is critical for this process, the regulation of VEGF has been
      unclear. In the present study, the relationship between VEGF and intraovarian
      cytokine, bone morphogenetic protein 7 (BMP-7) was investigated. Granulosa cells
      (GC), obtained from in vitro fertilization patients, were cultured with BMP-7
      followed by RNA extraction. Human umbilical vein endothelial cells (HUVECs) were
      also cultured with BMP-7 followed by RNA extraction, tube formation assay, or
      cell count analysis. The BMP-7 stimulated VEGF messenger RNA (mRNA) and protein
      expression in GC significantly. In HUVEC, BMP-7 increased an approximately 1.8
      fold in the cell number and induced the tube formation significantly compared to
      control. The BMP-7 also induced a 2-fold increase in VEGF receptor mRNA
      transcript relative abundance in HUVEC. The BMP-7, a theca cell-derived factor,
      may stimulate endothelial cell to form vasculature in the follicle via 2 distinct
      mechanisms, induction of VEGF expression in GC and increased sensitivity of
      endothelial cells to VEGF. 

PMID- 24023035
TI  - Pelvic floor musculature and bladder neck changes before and after continence
      recovery after radical prostatectomy in pelvic MRI.
AB  - PURPOSE: To evaluate the changes in pelvic floor anatomy using MRI before and
      after continence recovery after radical prostatectomy (RP). MATERIALS AND
      METHODS: Thirteen men with prostate cancer who underwent RP (mean age, 67.4 +/-
      8.8 years) volunteered for this study. Prostate MRIs were performed during the
      preoperative (i), incontinent (ii), and continent (iii) periods. The membranous
      urethra length (MUL), puborectalis muscle (PRM) thickness, and the position of
      the bladder neck in relation to the pubic bone (Dx) and the pubococcygeous line
      (Dy) were measured. We compared all parameters in the preoperative, incontinent,
      and continent periods. RESULTS: MUL2 and MUL3 was significantly longer compared
      with MUL1, although no difference was found between MUL2 and MUL3. PRM3 thickness
      was significantly increased compared with PRM2 thickness. The Dx of the
      continence period was shorter than that of the incontinence period. The Dy of the
      continence period was longer than that of the incontinence period. CONCLUSION:
      The PRM thickened and the bladder neck moved upward and forward during the
      continence period. The changes in PRM thickness and the position of bladder neck
      may play an important role in the recovery of continence after RP.

PMID- 24023037
TI  - Reduction in bradykinin generation during leukocytapheresis using novel
      cellsorba(TM) CS-180S: Effects of changing the filling solution.
AB  - We evaluated the bradykinin generation level during leukocytapheresis (LCAP)
      using novel Cellsorba(TM) CS-180S, which has sodium pyrosulfite and sodium
      carbonate as a filling solution. Subjects of this study were 14 rheumatoid
      arthritis patients. Regardless of the type of anticoagulant used, bradykinin
      levels were lower with the novel CS-180S than with the conventional CS-180S (28.7
      +/- 53.3 vs. 8.0 +/- 2.7 as the mean +/- standard deviation). When anticoagulants
      other than nafamostat mesilate were used with the conventional CS-180S,
      bradykinin levels increased at the column outlet compared with the column inlet,
      and adverse effects of bradykinin were seen in several cases. In contrast,
      bradykinin levels remained low and no bradykinin-associated adverse events were
      observed with the novel CS-180S. We recommend using the novel column instead of
      the conventional column in the treatment of LCAP.

PMID- 24023034
TI  - The relationship of a family history for hypertension, myocardial infarction, or
      stroke with cardiovascular physiology in young women.
AB  - Cardiovascular disease (CVD) and preeclampsia share several pathophysiologic risk
      factors. We examined family history (FH) and physiologic status in 60 healthy,
      nulliparous women to determine the relationship between FH and known risk factors
      for CVD. Data are presented as mean +/- standard error (SE). Decreased uterine
      blood flow was observed in women with FH of hypertension (+FH: 21.5 +/- 1.7, no
      FH: 33.3 +/- 9.0 mL/min; P = .04). Women reporting an FH of stroke showed
      increased alpha- and beta-adrenergic response, as measured by Valsalva maneuver
      (alpha: FH: 24.7 +/- 1.9, -FH: 18.9 +/- 1.1 mm Hg, P = .02; beta: FH: 22.0 +/-
      2.1, -FH: 16.9 +/- 1.4 mm Hg; P = .04), and increased cardiac output (4.83 +/-
      0.22 vs 4.31 +/- 0.12 L/min; P = .01). We identified no significant physiologic
      associations linked to an FH of myocardial infarction. Our observations show
      significant differences in physiologic characteristics in women with specific CVD
      family histories. These data, coupled with known heritable contributions to CVD
      and preeclampsia, suggest a distinct physiologic phenotype that may link
      preeclampsia risk with FH of CVD, independent of pregnancy. 

PMID- 24023036
TI  - Surfaceome profiling reveals regulators of neural stem cell function.
AB  - The composition of cell-surface proteins changes during lineage specification,
      altering cellular responses to their milieu. The changes that characterize
      maturation of early neural stem cells (NSCs) remain poorly understood. Here we
      use mass spectrometry-based cell surface capture technology to profile the cell
      surface of early NSCs and demonstrate functional requirements for several
      enriched molecules. Primitive NSCs arise from embryonic stem cells upon removal
      of Transforming growth factor-beta signaling, while definitive NSCs arise from
      primitive NSCs upon Lif removal and FGF addition. In vivo aggregation assays
      revealed that N-cadherin upregulation is sufficient for the initial exclusion of
      definitive NSCs from pluripotent ectoderm, while c-kit signaling limits progeny
      of primitive NSCs. Furthermore, we implicate EphA4 in primitive NSC survival
      signaling and Erbb2 as being required for NSC proliferation. This work elucidates
      several key mediators of NSC function whose relevance is confirmed on forebrain
      derived populations and identifies a host of other candidates that may regulate
      NSCs.

PMID- 24023038
TI  - Using genetically modified tomato crop plants with purple leaves for absolute
      weed/crop classification.
AB  - BACKGROUND: Weed/crop classification is considered the main problem in developing
      precise weed-management methodologies, because both crops and weeds share similar
      hues. Great effort has been invested in the development of classification models,
      most based on expensive sensors and complicated algorithms. However, satisfactory
      results are not consistently obtained due to imaging conditions in the field.
      RESULTS: We report on an innovative approach that combines advances in genetic
      engineering and robust image-processing methods to detect weeds and distinguish
      them from crop plants by manipulating the crop's leaf color. We demonstrate this
      on genetically modified tomato (germplasm AN-113) which expresses a purple leaf
      color. An autonomous weed/crop classification is performed using an invariant-hue
      transformation that is applied to images acquired by a standard consumer camera
      (visible wavelength) and handles variations in illumination intensities.
      CONCLUSION: The integration of these methodologies is simple and effective, and
      classification results were accurate and stable under a wide range of imaging
      conditions. Using this approach, we simplify the most complicated stage in image
      based weed/crop classification models.

PMID- 24023040
TI  - Impact of cancer-related fatigue on chemotherapy-induced nausea and vomiting in
      Asian cancer patients.
AB  - INTRODUCTION: Cancer-related fatigue (CRF) has been suggested to be associated
      with the occurrence of chemotherapy-induced nausea and vomiting (CINV). This
      study aims to evaluate the potential of CRF in predicting the occurrence of CINV.
      METHOD: This is a prospective, observational study. Recruited patients received
      moderately to highly emetogenic single-day chemotherapy regimens. On the day of
      chemotherapy, patients were instructed to provide a score (Likert scale of 0-10)
      to describe how CRF interfered with his or her ability to engage in daily
      activities and a score for how severe it was. Patients were then given a
      standardized 5-day diary to document their CINV events. RESULTS: A total of 473
      eligible patients (median age: 55 years, interquartile range (IQR): 48-61 years)
      were recruited, with most of the patients diagnosed with gastrointestinal (45%)
      and breast (37%) cancers. The median score of fatigue interference was 3 (IQR: 0
      5). After confounders were adjusted for, patients with low fatigue interference
      scores (<=3) were more likely to achieve complete protection (no nausea, no
      vomiting, and no breakthrough antiemetics) of CINV (adjusted odds ratio = 1.57,
      95%CI [1.05, 2.35], p = 0.027). CONCLUSION: This is the largest study to date to
      evaluate the association between CRF and CINV. Patients experiencing CRF
      possessed a higher risk of poor control for CINV.

PMID- 24023039
TI  - Conformational analysis of the full-length M2 protein of the influenza A virus
      using solid-state NMR.
AB  - The influenza A M2 protein forms a proton channel for virus infection and
      mediates virus assembly and budding. While extensive structural information is
      known about the transmembrane helix and an adjacent amphipathic helix, the
      conformation of the N-terminal ectodomain and the C-terminal cytoplasmic tail
      remains largely unknown. Using two-dimensional (2D) magic-angle-spinning solid
      state NMR, we have investigated the secondary structure and dynamics of full
      length M2 (M2FL) and found them to depend on the membrane composition. In 2D
      (13)C DARR correlation spectra, 1,2-dimyristoyl-sn-glycero-3-phosphocholine
      (DMPC)-bound M2FL exhibits several peaks at beta-sheet chemical shifts, which
      result from water-exposed extramembrane residues. In contrast, M2FL bound to
      cholesterol-containing membranes gives predominantly alpha-helical chemical
      shifts. Two-dimensional J-INADEQUATE spectra and variable-temperature (13)C
      spectra indicate that DMPC-bound M2FL is highly dynamic while the cholesterol
      containing membranes significantly immobilize the protein at physiological
      temperature. Chemical-shift prediction for various secondary-structure models
      suggests that the beta-strand is located at the N-terminus of the DMPC-bound
      protein, while the cytoplasmic domain is unstructured. This prediction is
      confirmed by the 2D DARR spectrum of the ectodomain-truncated M2(21-97), which no
      longer exhibits beta-sheet chemical shifts in the DMPC-bound state. We propose
      that the M2 conformational change results from the influence of cholesterol, and
      the increased helicity of M2FL in cholesterol-rich membranes may be relevant for
      M2 interaction with the matrix protein M1 during virus assembly and budding. The
      successful determination of the beta-strand location suggests that chemical-shift
      prediction is a promising approach for obtaining structural information of
      disordered proteins before resonance assignment.

PMID- 24023041
TI  - Ultrathin {001}-oriented bismuth tungsten oxide nanosheets as highly efficient
      photocatalysts.

PMID- 24023043
TI  - Stabile, thermoresponsive colloidal clusters: an unusual morphology of polymer
      dispersions.
AB  - A new class of colloidal polymeric particles consisting of polystyrene spheres
      grown in a poly(N-isopropyl acrylamide) precursor scaffold is synthesized via
      redox-initiated heterophase polymerization. The morphology and
      thermoresponsiveness of these assemblies is proven by electron microscopy
      investigations and temperature-dependent measurements of the change of both the
      speed of sound travelling through the dispersion and the hydrodynamic particle
      size. Electron microscopy (EM) micrographs (transmission and scanning EM as well
      cryo-scanning EM) prove the existence of colloidal clusters when the freeze-dried
      copolymer is redispersed in pure water. The clusters have a size of several
      micrometers, contain about 800 polystyrene particles with diameter below 100 nm,
      and show a highly reproducible thermoresponsive behavior with a lower critical
      solution temperature corresponding to that of pure poly(N-isopropyl acrylamide). 

PMID- 24023042
TI  - Highly local environmental variability promotes intrapopulation divergence of
      quantitative traits: an example from tropical rain forest trees.
AB  - BACKGROUND AND AIMS: In habitat mosaics, plant populations face environmental
      heterogeneity over short geographical distances. Such steep environmental
      gradients can induce ecological divergence. Lowland rainforests of the Guiana
      Shield are characterized by sharp, short-distance environmental variations
      related to topography and soil characteristics (from waterlogged bottomlands on
      hydromorphic soils to well-drained terra firme on ferralitic soils). Continuous
      plant populations distributed along such gradients are an interesting system to
      study intrapopulation divergence at highly local scales. This study tested (1)
      whether conspecific populations growing in different habitats diverge at
      functional traits, and (2) whether they diverge in the same way as congeneric
      species having different habitat preferences. METHODS: Phenotypic differentiation
      was studied within continuous populations occupying different habitats for two
      congeneric, sympatric, and ecologically divergent tree species (Eperua falcata
      and E. grandiflora, Fabaceae). Over 3000 seeds collected from three habitats were
      germinated and grown in a common garden experiment, and 23 morphological,
      biomass, resource allocation and physiological traits were measured. KEY RESULTS:
      In both species, seedling populations native of different habitats displayed
      phenotypic divergence for several traits (including seedling growth, biomass
      allocation, leaf chemistry, photosynthesis and carbon isotope composition). This
      may occur through heritable genetic variation or other maternally inherited
      effects. For a sub-set of traits, the intraspecific divergence associated with
      environmental variation coincided with interspecific divergence. CONCLUSIONS: The
      results indicate that mother trees from different habitats transmit divergent
      trait values to their progeny, and suggest that local environmental variation
      selects for different trait optima even at a very local spatial scale. Traits for
      which differentiation within species follows the same pattern as differentiation
      between species indicate that the same ecological processes underlie intra- and
      interspecific variation.

PMID- 24023044
TI  - Autoantibodies to RuvBL1 and RuvBL2: a novel systemic sclerosis-related antibody
      associated with diffuse cutaneous and skeletal muscle involvement.
AB  - OBJECTIVE: To identify and characterize a novel systemic sclerosis (SSc)-related
      autoantibody directed against a complex consisting of RuvBL1 and RuvBL2
      (RuvBL1/2) and to assess its clinical correlations. METHODS: We first analyzed
      316 consecutive patients with SSc who were evaluated at Kanazawa University
      Hospital. Controls included 290 patients with other connective tissue diseases,
      interstitial lung disease alone, or autoimmune hepatitis, and 50 healthy
      subjects. Autoantibody specificities were analyzed using RNA and protein
      immunoprecipitation assays. Autoimmune targets were affinity purified using
      patients' sera and subjected to liquid chromatography mass spectrometry. SSc
      patients in another institution in Japan and the University of Pittsburgh cohort
      were also included in analysis for evaluating clinical correlations. RESULTS: By
      protein immunoprecipitation assay, 6 SSc sera (1.9%) reacted with doublets with
      molecular weights of ~50 kd. Liquid chromatography mass spectrometry of the
      partially purified autoantigen and additional immunoblot-based analyses revealed
      that this antibody specificity recognized RuvBL1/2. Anti-RuvBL1/2 antibody was
      exclusively detected in SSc patients. SSc patients with anti-RuvBL1/2 in both the
      Japanese and Pittsburgh cohorts consistently had higher frequencies of SSc in
      overlap with myositis and diffuse skin thickening than those without anti
      RuvBL1/2. Compared with other autoantibodies related to SSc/myositis overlap
      (anti-PM-Scl and anti-Ku), anti-RuvBL1/2 was distinctive in terms of its
      associations with older age at SSc onset, male sex, and a high frequency of
      diffuse cutaneous involvement. CONCLUSION: Anti-RuvBL1/2 antibody is a novel SSc
      related autoantibody associated with a unique combination of clinical features,
      including myositis overlap and diffuse cutaneous involvement.

PMID- 24023045
TI  - A model of the relationship between weedy rice seed-bank dynamics and rice-crop
      infestation and damage in Jiangsu Province, China.
AB  - BACKGROUND: A heavy infestation of weedy rice leading to no harvested rice has
      never been predicted in China due to a lack of knowledge about the weedy rice
      seed bank. We studied the seed-bank dynamics of weedy rice for three consecutive
      years and analyzed the relationship between seed-bank density and population
      density in order to predict future weedy rice infestations of direct-seeded rice
      at six sites along the Yangtze River in Jiangsu Province, China. RESULTS: The
      seed-bank density of weedy rice in all six sites displayed an increasing trend
      with seasonal fluctuations. Weedy rice seeds found in the 0-10 cm soil layer
      contributed most to seedling emergence. An exponential curve expressed the
      relationship between cultivated rice yield loss and adult weedy rice density.
      Based on data collected during the weedy rice life-cycle, a semi-empirical
      mathematic model was developed that fits well with the experimental data in a way
      that could be used to predict seed-bank dynamics. CONCLUSIONS: By integrating the
      semi-empirical model and the exponential curve, weedy rice infestation levels and
      crop losses can be predicted based on the seed-bank dynamics so that a practical
      control can be adopted before rice planting.

PMID- 24023046
TI  - Scalable purification of the lantibiotic nisin and isolation of
      chemical/enzymatic cleavage fragments suitable for semi-synthesis.
AB  - Herein, we describe a scalable purification of the lantibiotic nisin via an
      extraction/precipitation approach using a biphasic system, which can be carried
      out up to 40-80 gram scale. This approach results in an at least tenfold
      enrichment of commercially available preparations of nisin, which usually contain
      only 2.5% of the desired peptide, to allow further purification by preparative
      HPLC. As a follow-up study, the enriched nisin sample was digested either by
      trypsin or chymotrypsin, or treated by CNBr, and these reactions were monitored
      by LC-MS to identify and characterize the obtained fragments. Two previously
      unknown cleavage sites have been identified: Asn20-Met21 and Met21-Lys22 for
      trypsin and chymotrypsin, respectively. Furthermore, a novel and convenient
      enzymatic approach to isolate the native nisin C-ring [nisin fragment (13-20)]
      was uncovered. Finally, by means of preparative HPLC, nisin fragments (1-12), (1
      20), (22-34), and (22-31) could be isolated and will be used in a semi-synthesis
      approach to elucidate the role of each fragment in the mode of action of nisin as
      an antimicrobial peptide.

PMID- 24023047
TI  - Expert consensus on best practices for post-acute rehabilitation after total hip
      and knee arthroplasty: a Canada and United States Delphi study.
AB  - OBJECTIVE: To synthesize professional and patient expertise with available
      evidence to recommend best practices for post-acute rehabilitation following
      primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) for
      osteoarthritis (OA). METHODS: Two expert panels of clinicians, researchers, and
      patients from Canada and the US participated in a 3-round, online Delphi survey.
      RESULTS: Consensus was reached on 22 THA and 24 TKA best practice key statements.
      Recommendations common to both procedures included the need for supervised
      rehabilitation interventions provided by trained health professionals early after
      discharge from the acute care setting to optimize patient outcomes. Personal and
      environmental contextual factors were identified as influencing the process and
      outcomes of THA and TKA rehabilitation. Routine outcome assessment was
      recommended and several standardized outcome tools identified. Short-term
      followup care in the first 2 years postsurgery was recommended for both
      procedures. Specifics on timing, rehabilitation providers, need for long-term
      followup, and interventions differed for THA and TKA. Some recommendations
      received different levels of support based on the type of panelist (patient,
      physical therapist, surgeon), professional role (clinician, researcher), and/or
      country. CONCLUSION: A rigorous consensus method led to key recommendations for
      post-acute rehabilitation after primary THA and TKA for OA, which together with
      available evidence and acknowledgment of contextual factors will inform the
      development of clinical practice guidelines. This is an important step toward
      reducing practice variation, closing the evidence-practice gap, and improving the
      quality of rehabilitation services after THA and TKA.

PMID- 24023048
TI  - A sulfated ZrO2 hollow nanostructure as an acid catalyst in the dehydration of
      fructose to 5-hydroxymethylfurfural.
AB  - Mesoporous hollow colloidal particles with well-defined characteristics have
      potential use in many applications. In liquid-phase catalysis, in particular,
      they can provide a large active surface area, reduced diffusion resistance,
      improved accessibility to reactants, and excellent dispersity in reaction media.
      Herein, we report the tailored synthesis of sulfated ZrO2 hollow nanostructures
      and their catalytic applications in the dehydration of fructose. ZrO2 hollow
      nanoshells with controllable thickness were first synthesized through a robust
      sol-gel process. Acidic functional groups were further introduced to the surface
      of hollow ZrO2 shells by sulfuric acid treatment followed by calcination. The
      resulting sulfated ZrO2 hollow particles showed advantageous properties for
      liquid-phase catalysis, such as well-maintained structural integrity, good
      dispersity, favorable mesoporosity, and a strongly acidic surface. By controlling
      the synthesis and calcination conditions and optimizing the properties of
      sulfated ZrO2 hollow shells, we have been able to design superacid catalysts with
      superior performance in the dehydration of fructose to 5-hydroxymethyfurfural
      than the solid sulfated ZrO2 nanocatalyst. 

PMID- 24023049
TI  - Facile preparation of cobaltocenium-containing polyelectrolyte via click
      chemistry and RAFT polymerization.
AB  - A facile method to prepare cationic cobaltocenium-containing polyelectrolyte is
      reported. Cobaltocenium monomer with methacrylate is synthesized by copper
      catalyzed azide-alkyne cycloaddition (CuAAC) reaction between 2-azidoethyl
      methacrylate and ethynylcobaltocenium hexafluorophosphate. Further controlled
      polymerization is achieved by reversible addition-fragmentation chain transfer
      polymerization (RAFT) by using cumyl dithiobenzoate (CDB) as a chain transfer
      agent. Kinetic study demonstrates the controlled/living process of
      polymerization. The obtained side-chain cobaltocenium-containing polymer is a
      metal-containing polyelectrolyte that shows characteristic redox behavior of
      cobaltocenium. 

PMID- 24023050
TI  - Mechanisms of trazodone-induced cytotoxicity and the protective effects of
      melatonin and/or taurine toward freshly isolated rat hepatocytes.
AB  - It has been reported that the bioactive intermediate metabolites of trazodone
      might cause hepatotoxicity. This study was designed to investigate the exact
      mechanism of hepatocellular injury induced by trazodone as well as the protective
      effects of taurine and/or melatonin against this toxicity. Freshly isolated rat
      hepatocytes were used. Trazodone was cytotoxic and caused cell death with LC50 of
      300 um within 2 h. Trazodone caused an increase in reactive oxygen species (ROS)
      formation, malondialdehyde accumulation, depletion of intracellular reduced
      glutathione (GSH), rise of oxidized glutathione disulfide (GSSG), and a decrease
      in mitochondrial membrane potential, which confirms the role of oxidative stress
      in trazodone-induced cytotoxicity. Preincubation of hepatocytes with taurine
      prevented ROS formation, lipid peroxidation, depletion of intracellular reduced
      GSH, and increase of oxidized GSSG. Taurine could also protect mitochondria
      against trazodone-induced toxicity. Administration of melatonin reduced the toxic
      effects of trazodone in isolated rat hepatocytes.

PMID- 24023051
TI  - Strong association of health literacy with functional status among rheumatoid
      arthritis patients: a cross-sectional study.
AB  - OBJECTIVE: Studies linking health literacy to outcomes in rheumatoid arthritis
      (RA) have been underpowered and have not adequately accounted for confounders. We
      examined the association of health literacy with functional status in 6,052
      subjects participating in a prospective observational study, controlling for
      numerous important covariates. METHODS: Using linear regression, we analyzed the
      cross-sectional association of health literacy, as measured by 2 validated single
      item literacy screening questions (SILS1 and SILS2), and functional status,
      assessed by the Health Assessment Questionnaire (HAQ) disability index. Subjects
      reported demographics, comorbidities, social support, educational attainment,
      visual problems, and memory problems, as well as use of prednisone, disease
      modifying antirheumatic drugs, and biologic agents. Each SILS measure was forced
      into the final model. RESULTS: Low health literacy was present in 7.0% and 4.3%
      of subjects (per SILS1 and SILS2, respectively). When controlling for all
      covariates, low health literacy was associated with a 0.376-point greater HAQ
      score, compared to subjects with adequate health literacy (95% confidence
      interval 0.306, 0.447; P < 0.001). This relationship persisted, even after
      modeling educational attainment. Results were similar for the 2 SILS instruments.
      Low health literacy was also associated with poorer self-reported adherence to RA
      medications. Visual and memory problems were associated with worse functional
      status. CONCLUSION: Health literacy was more strongly associated with functional
      status than prednisone use, smoking history, and biologic agent use, and
      independent of educational attainment. Health literacy may play an important role
      in understanding functional status in RA patients. Single-item questions amenable
      to use in the clinical setting may identify subjects with low health literacy,
      who are at risk for poor RA outcomes.

PMID- 24023052
TI  - Towards stable catalysts for aqueous phase conversion of ethylene glycol for
      renewable hydrogen.
AB  - Aqueous-phase reforming of ethylene glycol over alumina-supported Pt-based
      catalysts is reported. Performance of the catalysts is investigated by conducting
      kinetics and in situ attenuated total reflectance (ATR)-IR spectroscopic
      analysis. Pt/gamma-Al2 O3 is unstable under APR conditions (270  degrees C, 90
      bar) and undergoes phase transformation to boehmite [AlO(OH)]. This conversion of
      alumina is studied in situ by using ATR-IR spectroscopy; transition into boehmite
      proceeds even at milder conditions (210  degrees C, 40 bar). Pt/gamma-Al2 O3
      deactivates irreversibly because the Pt surface area decreases owing to an
      increasing metal particle size and coverage with boehmite. However, Pt supported
      on boehmite itself shows stable activity. Surprisingly, the rate of formation of
      hydrogen per Pt surface atom is significantly higher on boehmite compared to an
      alumina-supported catalyst. This observation seems correlated to both increased
      concentration of surface OH groups as well as to enhanced oxidation of Pt when
      comparing Pt/gamma-Al2 O3 with Pt/AlO(OH).

PMID- 24023053
TI  - Tumor necrosis factor alpha inhibitor use and decreased risk for incident
      coronary events in rheumatoid arthritis.
AB  - OBJECTIVE: To determine the association of tumor necrosis factor alpha (TNFalpha)
      inhibitors with risk for cardiovascular disease (CVD) in rheumatoid arthritis
      (RA) patients. METHODS: A retrospective cohort of 2,101 incident RA patients was
      established. Medication exposure was categorized into the following groups:
      TNFalpha inhibitors alone or in combination with methotrexate (MTX; aTNF group);
      MTX alone or in combination with other nonbiologic disease-modifying
      antirheumatic drugs (DMARDs; MTX group); and no MTX, nonbiologic DMARDs
      (reference group). Primary outcome was adjudicated incident coronary artery
      disease (CAD), defined as myocardial infarction, unstable angina, or coronary
      revascularization procedure. Secondary outcome was adjudicated incident CVD,
      defined as a composite of CAD, stroke, transient ischemic attack, abdominal
      aortic aneurysm, peripheral arterial disease, or arterial revascularization
      procedure. Cox regression models were used to calculate the hazard ratio for CAD
      and CVD for the aTNF and MTX groups compared to the reference group. RESULTS:
      There were 46 incident CAD and 82 incident CVD events. Adjusting for covariates
      associated with CAD and CVD, the hazard ratio for incident CAD was 0.45 (95%
      confidence interval [95% CI] 0.21-0.96) for the aTNF group and 0.54 (95% CI 0.27
      1.09) for the MTX group compared to the reference group. Use of TNFalpha
      inhibitors for >16.1 months was associated with a relative risk for CAD of 0.18
      (95% CI 0.06-0.50) and for CVD of 0.31 (95% CI 0.15-0.65) compared to the
      reference group. A similar, although not significant, trend was seen with the MTX
      group. CONCLUSION: Use of TNFalpha inhibitors is associated with a decreased risk
      for CAD in RA; the risk decreases further with long-term use. This should be
      considered when weighing the risks versus benefits of these medications.

PMID- 24023058
TI  - UPLC-MS/MS method for determination of bepotastine in human plasma.
AB  - A sensitive and rapid method for quantitation of bepotastine in human plasma has
      been established using ultra performance liquid chromatography-electrospray
      ionization tandem mass spectrometry (UPLC-ESI-MS/MS). Valsartan was used as an
      internal standard. Bepotastine and internal standard in plasma sample were
      extracted using ethylacetate (liquid-liquid extraction). A centrifuged upper
      layer was then evaporated and reconstituted with the mobile phase of acetonitrile
      -5 mM ammonium formate (pH 3.5) (85:15, v/v). The reconstituted samples were
      injected into a phenyl column. Using MS/MS in the multiple reaction monitoring
      mode, bepotastine and valsartan were detected without severe interference from
      human plasma matrix. Bepotastine produced a protonated precursor ion ([M+H](+))
      at m/z 389 and a corresponding product ion at m/z 167. And the internal standard
      produced a protonated precursor ion ([M+H](+)) at m/z 436 and a corresponding
      product ion at m/z 291. Detection of bepotastine in human plasma by the UPLC-ESI
      MS/MS method was accurate and precise with a quantitation limit of 0.2 ng/mL. The
      validation, reproducibility, stability and recovery of the method were evaluated.
      The method has been successfully applied to pharmacokinetic studies of
      bepotastine in human plasma.

PMID- 24023059
TI  - Ecological monitoring in Peru.

PMID- 24023061
TI  - U1 small nuclear ribonucleoprotein complex and RNA splicing alterations in
      Alzheimer's disease.
AB  - Deposition of insoluble protein aggregates is a hallmark of neurodegenerative
      diseases. The universal presence of beta-amyloid and tau in Alzheimer's disease
      (AD) has facilitated advancement of the amyloid cascade and tau hypotheses that
      have dominated AD pathogenesis research and therapeutic development. However, the
      underlying etiology of the disease remains to be fully elucidated. Here we report
      a comprehensive study of the human brain-insoluble proteome in AD by mass
      spectrometry. We identify 4,216 proteins, among which 36 proteins accumulate in
      the disease, including U1-70K and other U1 small nuclear ribonucleoprotein (U1
      snRNP) spliceosome components. Similar accumulations in mild cognitive impairment
      cases indicate that spliceosome changes occur in early stages of AD. Multiple U1
      snRNP subunits form cytoplasmic tangle-like structures in AD but not in other
      examined neurodegenerative disorders, including Parkinson disease and
      frontotemporal lobar degeneration. Comparison of RNA from AD and control brains
      reveals dysregulated RNA processing with accumulation of unspliced RNA species in
      AD, including myc box-dependent-interacting protein 1, clusterin, and presenilin
      1. U1-70K knockdown or antisense oligonucleotide inhibition of U1 snRNP increases
      the protein level of amyloid precursor protein. Thus, our results demonstrate
      unique U1 snRNP pathology and implicate abnormal RNA splicing in AD pathogenesis.

PMID- 24023063
TI  - Development of a histone deacetylase 6 inhibitor and its biological effects.
AB  - Development of isoform-selective histone deacetylase (HDAC) inhibitors is
      important in elucidating the function of individual HDAC enzymes and their
      potential as therapeutic agents. Among the eleven zinc-dependent HDACs in humans,
      HDAC6 is structurally and functionally unique. Here, we show that a hydroxamic
      acid-based small-molecule N-hydroxy-4-(2-[(2-hydroxyethyl)(phenyl)amino]-2
      oxoethyl)benzamide (HPOB) selectively inhibits HDAC6 catalytic activity in vivo
      and in vitro. HPOB causes growth inhibition of normal and transformed cells but
      does not induce cell death. HPOB enhances the effectiveness of DNA-damaging
      anticancer drugs in transformed cells but not normal cells. HPOB does not block
      the ubiquitin-binding activity of HDAC6. The HDAC6-selective inhibitor HPOB has
      therapeutic potential in combination therapy to enhance the potency of anticancer
      drugs. 

PMID- 24023064
TI  - Uracil in duplex DNA is a substrate for the nucleotide incision repair pathway in
      human cells.
AB  - Spontaneous hydrolytic deamination of cytosine to uracil (U) in DNA is a constant
      source of genome instability in cells. This mutagenic process is greatly enhanced
      at high temperatures and in single-stranded DNA. If not repaired, these uracil
      residues give rise to C -> T transitions, which are the most common spontaneous
      mutations occurring in living organisms and are frequently found in human tumors.
      In the majority of species, uracil residues are removed from DNA by specific
      uracil-DNA glycosylases in the base excision repair pathway. Alternatively, in
      certain archaeal organisms, uracil residues are eliminated by
      apurinic/apyrimidinic (AP) endonucleases in the nucleotide incision repair
      pathway. Here, we characterized the substrate specificity of the major human AP
      endonuclease 1, APE1, toward U in duplex DNA. APE1 cleaves oligonucleotide
      duplexes containing a single U?G base pair; this activity depends strongly on the
      sequence context and the base opposite to U. The apparent kinetic parameters of
      the reactions show that APE1 has high affinity for DNA containing U but cleaves
      the DNA duplex at an extremely low rate. MALDI-TOF MS analysis of the reaction
      products demonstrated that APE1-catalyzed cleavage of a U?G duplex generates the
      expected DNA fragments containing a 5'-terminal deoxyuridine monophosphate. The
      fact that U in duplex DNA is recognized and cleaved by APE1 in vitro suggests
      that this property of the exonuclease III family of AP endonucleases is
      remarkably conserved from Archaea to humans. We propose that nucleotide incision
      repair may act as a backup pathway to base excision repair to remove uracils
      arising from cytosine deamination.

PMID- 24023065
TI  - Ammonia binding to the oxygen-evolving complex of photosystem II identifies the
      solvent-exchangeable oxygen bridge (MU-oxo) of the manganese tetramer.
AB  - The assignment of the two substrate water sites of the tetra-manganese penta
      oxygen calcium (Mn4O5Ca) cluster of photosystem II is essential for the
      elucidation of the mechanism of biological O-O bond formation and the subsequent
      design of bio-inspired water-splitting catalysts. We recently demonstrated using
      pulsed EPR spectroscopy that one of the five oxygen bridges (MU-oxo) exchanges
      unusually rapidly with bulk water and is thus a likely candidate for one of the
      substrates. Ammonia, a water analog, was previously shown to bind to the Mn4O5Ca
      cluster, potentially displacing a water/substrate ligand [Britt RD, et al. (1989)
      J Am Chem Soc 111(10):3522-3532]. Here we show by a combination of EPR and time
      resolved membrane inlet mass spectrometry that the binding of ammonia perturbs
      the exchangeable MU-oxo bridge without drastically altering the binding/exchange
      kinetics of the two substrates. In combination with broken-symmetry density
      functional theory, our results show that (i) the exchangable MU-oxo bridge is O5
      {using the labeling of the current crystal structure [Umena Y, et al. (2011)
      Nature 473(7345):55-60]}; (ii) ammonia displaces a water ligand to the outer
      manganese (MnA4-W1); and (iii) as W1 is trans to O5, ammonia binding elongates
      the MnA4-O5 bond, leading to the perturbation of the MU-oxo bridge resonance and
      to a small change in the water exchange rates. These experimental results support
      O-O bond formation between O5 and possibly an oxyl radical as proposed by
      Siegbahn and exclude W1 as the second substrate water. 

PMID- 24023066
TI  - EGFR lung cancer mutants get specialized.

PMID- 24023067
TI  - Arabidopsis semidwarfs evolved from independent mutations in GA20ox1, ortholog to
      green revolution dwarf alleles in rice and barley.
AB  - Understanding the genetic bases of natural variation for developmental and stress
      related traits is a major goal of current plant biology. Variation in plant
      hormone levels and signaling might underlie such phenotypic variation occurring
      even within the same species. Here we report the genetic and molecular basis of
      semidwarf individuals found in natural Arabidopsis thaliana populations. Allelism
      tests demonstrate that independent loss-of-function mutations at GA locus 5
      (GA5), which encodes gibberellin 20-oxidase 1 (GA20ox1) involved in the last
      steps of gibberellin biosynthesis, are found in different populations from
      southern, western, and northern Europe; central Asia; and Japan. Sequencing of
      GA5 identified 21 different loss-of-function alleles causing semidwarfness
      without any obvious general tradeoff affecting plant performance traits. GA5
      shows signatures of purifying selection, whereas GA5 loss-of-function alleles can
      also exhibit patterns of positive selection in specific populations as shown by
      Fay and Wu's H statistics. These results suggest that antagonistic pleiotropy
      might underlie the occurrence of GA5 loss-of-function mutations in nature.
      Furthermore, because GA5 is the ortholog of rice SD1 and barley Sdw1/Denso green
      revolution genes, this study illustrates the occurrence of conserved adaptive
      evolution between wild A.thaliana and domesticated plants. 

PMID- 24023069
TI  - Shock whilst gardening--implantable defibrillators & lawn mowers.
AB  - Electromagnetic interference with implantable cardioverter defibrillators (ICDs)
      can cause inappropriate shock delivery or temporary inhibition of ICD functions.
      We present a case of electromagnetic interference between a lawn mower and an ICD
      resulting in an inappropriate discharge of the device due to erroneous detection
      of ventricular fibrillation. 

PMID- 24023068
TI  - HIF1alpha is required for osteoclast activation by estrogen deficiency in
      postmenopausal osteoporosis.
AB  - In women, estrogen deficiency after menopause frequently accelerates osteoclastic
      bone resorption, leading to osteoporosis, the most common skeletal disorder.
      However, mechanisms underlying osteoporosis resulting from estrogen deficiency
      remain largely unknown. Here we show that in bone-resorbing osteoclasts, estrogen
      dependent destabilization of hypoxia-inducible factor 1 alpha (HIF1alpha), which
      is unstable in the presence of oxygen, plays a pivotal role in promoting bone
      loss in estrogen-deficient conditions. In vitro, HIF1alpha was destabilized by
      estrogen treatment even in hypoxic conditions, and estrogen loss in
      ovariectomized (Ovx) mice stabilized HIF1alpha in osteoclasts and promoted their
      activation and subsequent bone loss in vivo. Osteoclast-specific HIF1alpha
      inactivation antagonized bone loss in Ovx mice and osteoclast-specific estrogen
      receptor alpha deficient mice, both models of estrogen-deficient osteoporosis.
      Oral administration of a HIF1alpha inhibitor protected Ovx mice from osteoclast
      activation and bone loss. Thus, HIF1alpha represents a promising therapeutic
      target in osteoporosis. 

PMID- 24023070
TI  - Recurrence of digoxin toxicity following treatment with digoxin immune fab in a
      patient with renal impairment.
AB  - In patients with chronic digoxin toxicity, especially in the presence of renal
      impairment, a prolonged duration of continuous monitoring is required with
      consideration given to further doses of immune fab if necessary for re-emergence
      of toxicity.

PMID- 24023071
TI  - Olfactory disturbance related to pyrazinamide.

PMID- 24023072
TI  - The California breast density information group: a collaborative response to the
      issues of breast density, breast cancer risk, and breast density notification
      legislation.
AB  - In anticipation of breast density notification legislation in the state of
      California, which would require notification of women with heterogeneously and
      extremely dense breast tissue, a working group of breast imagers and breast
      cancer risk specialists was formed to provide a common response framework. The
      California Breast Density Information Group identified key elements and
      implications of the law, researching scientific evidence needed to develop a
      robust response. In particular, issues of risk associated with dense breast
      tissue, masking of cancers by dense tissue on mammograms, and the efficacy,
      benefits, and harms of supplementary screening tests were studied and consensus
      reached. National guidelines and peer-reviewed published literature were used to
      recommend that women with dense breast tissue at screening mammography follow
      supplemental screening guidelines based on breast cancer risk assessment. The
      goal of developing educational materials for referring clinicians and patients
      was reached with the construction of an easily accessible Web site that contains
      information about breast density, breast cancer risk assessment, and
      supplementary imaging. This multi-institutional, multidisciplinary approach may
      be useful for organizations to frame responses as similar legislation is passed
      across the United States. Online supplemental material is available for this
      article.

PMID- 24023073
TI  - Acute kidney injury: arterial spin labeling to monitor renal perfusion impairment
      in mice-comparison with histopathologic results and renal function.
AB  - PURPOSE: To determine if arterial spin-labeling (ASL) magnetic resonance (MR)
      imaging can show serial changes in renal perfusion in mice with ischemia-induced
      acute kidney injury (AKI) and to compare imaging results with those of renal
      histologic examination and inulin and para-aminohippuric acid (PAH) clearance.
      MATERIALS AND METHODS: In this animal care committee-approved study, AKI was
      induced in C57Bl/6 mice (n = 26) by clamping the right renal pedicle for 35
      minutes for moderate (n = 16) or 45 minutes (n = 11) for severe AKI. Renal
      perfusion was measured in 10 animals with moderate and seven animals with severe
      AKI before and at five time points 1-28 days after surgery by using ASL with a 7
      T MR imaging unit. Kidney volume loss and histologic evidence of acute tubular
      injury were assessed. Inulin and PAH clearance was determined in four animals
      with moderate and six animals with severe AKI to evaluate renal function and
      plasma flow for statistical analysis. Repeated measures analysis of variance,
      unpaired t tests, and correlation analysis were used. RESULTS: Renal perfusion
      values at day 7 were significantly reduced after moderate (56% +/- 8; P < .01)
      and severe (33% +/- 6; P < .001) AKI compared with presurgery values. Renal
      perfusion had returned to baseline levels at day 21 after moderate (96% +/- 14)
      and remained compromised until day 28 after severe (46 % +/- 9; P < .05) AKI. At
      day 28, for moderate versus severe AKI, kidney volume (84% +/- 6 vs 60% +/- 5; P
      < .05), degree of tubular injury (5.6% +/- 1.8 vs 15.8% +/- 2.4; P < .01), and
      inulin and para-aminohippuric acid clearance (47.5 uL/min +/- 5.6 vs 7.3 uL/min
      +/- 2.7; P < .001 and 100.8 uL/min +/- 24.3 vs 4.8 uL/min +/- 1.0; P < .001,
      respectively) were significantly different. Relative renal perfusion at days 7-28
      significantly correlated with kidney volume loss (P < .01) and tubular injury (P
      < .05) 4 weeks after AKI. CONCLUSION: ASL allows evaluation of renal perfusion
      impairment associated with kidney volume loss and histologic changes after AKI in
      mice and may serve as a noninvasive biomarker for AKI.

PMID- 24023074
TI  - Diabetes mellitus: long-term prognostic value of whole-body MR imaging for the
      occurrence of cardiac and cerebrovascular events.
AB  - PURPOSE: To study the predictive value of whole-body magnetic resonance (MR)
      imaging for the occurrence of cardiac and cerebrovascular events in a cohort of
      patients with diabetes mellitus (DM). MATERIALS AND METHODS: This HIPAA-compliant
      study was approved by the institutional review board. Informed consent was
      obtained from all patients before enrollment into the study. The authors followed
      up 65 patients with DM (types 1 and 2) who underwent a comprehensive, contrast
      material-enhanced whole-body MR imaging protocol, including brain, cardiac, and
      vascular sequences at baseline. Follow-up was performed by phone interview. The
      primary endpoint was a major adverse cardiac and cerebrovascular event (MACCE),
      which was defined as composite cardiac-cerebrovascular death, myocardial
      infarction, cerebrovascular event, or revascularization. MR images were assessed
      for the presence of systemic atherosclerotic vessel changes, white matter
      lesions, and myocardial changes. Kaplan-Meier survival and Cox regression
      analyses were performed to determine associations. RESULTS: Follow-up was
      completed in 61 patients (94%; median age, 67.5 years; 30 women [49%]; median
      follow-up, 70 months); 14 of the 61 patients (23%) experienced MACCE. Although
      normal whole-body MR imaging excluded MACCE during the follow-up period (0%; 95%
      confidence interval [CI]: 0%, 17%), any detectable ischemic and/or
      atherosclerotic changes at whole-body MR imaging (prevalence, 66%) conferred a
      cumulative event rate of 20% at 3 years and 35% at 6 years. Whole-body MR imaging
      summary estimate of disease was strongly predictive for MACCE (one increment of
      vessel score and each territory with atherosclerotic changes: hazard ratio, 13.2
      [95% CI: 4.5, 40.1] and 3.9 [95% CI: 2.2, 7.5], respectively), also beyond
      clinical characteristics as well as individual cardiac or cerebrovascular MR
      findings. CONCLUSION: These initial data indicate that disease burden as assessed
      with whole-body MR imaging confers strong prognostic information in patients with
      DM. Online supplemental material is available for this article.

PMID- 24023246
TI  - Maternal omega-3 fatty acid intake increases placental labyrinthine antioxidant
      capacity but does not protect against fetal growth restriction induced by
      placental ischaemia-reperfusion injury.
AB  - Placental oxidative stress plays a key role in the pathophysiology of several
      placenta-related disorders. Oxidative stress occurs when excess reactive oxygen
      species (ROS) damages cellular components, an outcome limited by antioxidant
      enzymes; mitochondrial uncoupling protein 2 (UCP2) also limits ROS production. We
      recently reported that maternal dietary omega-3 polyunsaturated fatty acid (n-3
      PUFA) supplementation reduced placental oxidative damage and enhanced fetal and
      placental growth in the rats. Here, we examined the effect of n-3 PUFAs on
      placental antioxidant defences and whether n-3 PUFA supplementation could prevent
      growth restriction induced by placental ischaemia-reperfusion (IR), a known
      inducer of oxidative stress. Rats were fed either standard or high-n-3 PUFA diets
      from day 1 of pregnancy. Placentas were collected on days 17 and 22 in untreated
      pregnancies (term=day 23) and at day 22 following IR treatment on day 17.
      Expression of several antioxidant enzyme genes (Sod1, Sod2, Sod3, Cat, Txn1 and
      Gpx3) and Ucp2 was measured by quantitative RT-PCR in the placental labyrinth
      zone (LZ) and junctional zone (JZ). Cytosolic superoxide dismutase (SOD),
      mitochondrial SOD and catalase (CAT) activities were also analyzed. Maternal n-3
      PUFA supplementation increased LZ mRNA expression of Cat at both gestational days
      (2- and 1.5-fold respectively; P<0.01) and female Sod2 at day 22 (1.4-fold,
      P<0.01). Cytosolic SOD activity increased with n-3 PUFA supplementation at day 22
      (1.3-fold, P<0.05). Sod1 and Txn1 expression decreased marginally (30 and 22%,
      P<0.05). JZ antioxidant defences were largely unaffected by diet. Despite
      increased LZ antioxidant defences, maternal n-3 PUFA supplementation did not
      protect against placental IR-induced growth restriction of the fetus and
      placental LZ. 

PMID- 24023247
TI  - The EULAR Sjogren's syndrome patient reported index as an independent determinant
      of health-related quality of life in primary Sjogren's syndrome patients: in
      comparison with non-Sjogren's sicca patients.
AB  - OBJECTIVE: To investigate the significant determinants of health-related quality
      of life (HRQOL) and the association of the EULAR Sjogren's syndrome patient
      reported index (ESSPRI) with clinical parameters including HRQOL in Korean
      patients with primary Sjogren's syndrome (pSS) compared with non-SS sicca
      patients. METHODS: We prospectively analysed 104 pSS and 42 non-SS sicca
      patients. Clinical data including Short Form 36 (SF-36) scores, self-assessments
      for symptoms and ESSPRI were cross-sectionally collected. RESULTS: Although most
      self-assessments and HRQOL statuses were comparable, different association
      patterns between HRQOL and symptoms were observed in pSS and non-SS sicca
      patients. pSS patients with low HRQOL had significantly higher ESSPRI scores [P =
      7.6 * 10(-6) for physical component summary (PCS) subgroups and P = 0.0015 for
      mental component summary (MCS) subgroups] and ESSPRI scores showed a significant
      association with all SF-36 scales in pSS patients (all P <= 0.0020). Moreover, in
      multivariate linear regression analyses, ESSPRI (P = 0.035) and depression (P =
      4.1 * 10(-14)) were significantly correlated with the PCS and the MCS,
      respectively. However, in the non-SS sicca group, xerostomia inventory (XI)
      scores were higher in the low PCS subgroup (P = 0.031) and this correlated with
      five SF-36 scales (all P <= 0.046). XI scores (P = 0.0039) and anxiety (P = 7.9 *
      10(-10)) were the main determinants of the PCS and MCS, respectively. CONCLUSION:
      HRQOL levels were differentially associated with clinical facets in pSS and non
      SS sicca patients, although the groups had similar clinical symptoms and HRQOL
      reduction. Because depression and ESSPRI are major determinants of HRQOL in
      Korean pSS patients, ESSPRI is suggested to be disease-specific for pSS.

PMID- 24023248
TI  - Immunoglobulin maintenance therapy in long-standing complex regional pain
      syndrome, an open study.

PMID- 24023249
TI  - Characterization and expression profiling of cucumber kinesin genes during early
      fruit development: revealing the roles of kinesins in exponential cell production
      and enlargement in cucumber fruit.
AB  - Rapid cell division and expansion in early fruit development are important phases
      for cucumber fruit yield and quality. Kinesin proteins are microtubule-based
      motors responsible for modulating cell division and enlargement. In this work,
      the candidate kinesin genes involved in rapid cell division and expansion during
      cucumber fruit development were investigated. The morphological and cellular
      changes during early fruit development were compared in four cucumber genotypes
      with varied fruit size. The correlation between the expression profiles of
      cucumber kinesin genes and cellular changes in fruit was investigated. Finally,
      the biochemical characteristics and subcellular localizations of three candidate
      kinesins were studied. The results clarified the morphological and cellular
      changes during early cucumber fruit development. This study found that CsKF2
      CsKF6 were positively correlated with rapid cell production; CsKF1 and CsKF7
      showed a strongly positive correlation with rapid cell expansion. The results
      also indicated that CsKF1 localized to the plasma membrane of fast-expanding
      fruit cells, that CsKF2 might play a role in fruit chloroplast division, and that
      CsKF3 is involved in the function or formation of phragmoplasts in fruit
      telophase cells. The results strongly suggest that specific fruit-enriched
      kinesins are specialized in their functions in rapid cell division and expansion
      during cucumber fruit development. 

PMID- 24023250
TI  - Lateral root formation and growth of Arabidopsis is redundantly regulated by
      cytokinin metabolism and signalling genes.
AB  - The plant root system is important for the uptake of water and nutrients and the
      anchoring of plants in the soil. Lateral roots (LRs) contribute considerably to
      root system architecture. Their post-embryonic formation is regulated by hormones
      and environmental cues. The hormone cytokinin influences LR formation and growth
      in Arabidopsis thaliana on different levels by disturbing cell division activity
      and pattern formation. This includes inhibition of the first formative cell
      division of pericycle founder cells and inhibition of the outgrowth of young LR
      primordia. Mutant analysis revealed that the cytokinin biosynthesis genes IPT3
      and IPT5 and all three cytokinin receptor genes (AHK2, AHK3, and CRE1/AHK4) act
      redundantly during LR initiation. Mutation of AHK2 and AHK3 caused increased
      auxin sensitivity of LR formation, corroborating the functional relevance of
      auxin-cytokinin interaction during LR formation. In contrast, LR development of
      cytokinin receptor mutants in response to other hormones was mostly similar to
      that of the wild type, which is consistent with separate response pathways. A
      noticeable exception was an increased sensitivity of LR elongation to
      brassinolide in ahk2 ahk3 mutants indicating antagonistic action of cytokinin and
      brassinosteroid. It is proposed that the multilevel redundancy of the cytokinin
      system in modulating LR formation reflects its role in mediating environmental
      cues. 

PMID- 24023252
TI  - Phylogeography of mugwort (Artemisia indica), a native pioneer herb in Japan.
AB  - Many phylogeographic studies of various tree species have been conducted to
      elucidate the locations of refugia and the colonization patterns during the
      Pleistocene. However, only a few large-scale phylogeographic studies have been
      conducted on herbaceous plants, especially scarce on herbs that are adapted to
      disturbance. Artemisia indica is a fast-growing perennial herb found in open
      habitats. To examine the basic information on the genetic structure of this
      species, we investigated the chloroplast DNA variation within and among
      populations across Japan. We detected 26 haplotypes in 604 individuals from 28
      Japanese populations. The haplotype A1 had wide geographic distribution, and its
      close relatives were locally present. Some putative ancestral lineages were found
      mainly in the Kyushu region. This may be because several lineages migrated from
      the Eurasian continent to the northern coast in Kyushu via the Korean peninsula
      during the Pleistocene, and the A1 haplotype expanded northward, whereas others
      remained in southern areas. Phylogenetic distant haplotypes were present mainly
      in the Kanto region. Because the geographic distribution pattern of these
      haplotypes in this region is believed to be unnatural, these haplotypes may be
      derived from commercial sources for re-vegetation during the last few decades. 

PMID- 24023251
TI  - Reduced frontal glutamate + glutamine and N-acetylaspartate levels in patients
      with chronic schizophrenia but not in those at clinical high risk for psychosis
      or with first-episode schizophrenia.
AB  - Changes in brain pathology as schizophrenia progresses have been repeatedly
      suggested by previous studies. Meta-analyses of previous proton magnetic
      resonance spectroscopy ((1)H MRS) studies at each clinical stage of schizophrenia
      indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic
      metabolites change progressively. However, to our knowledge, no single study has
      addressed the possible differences in (1)H MRS abnormalities in subjects at 3
      different stages of disease, including those at ultrahigh risk for psychosis
      (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia
      (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their
      demographically matched 3 independent control groups (n = 26/19/28 for the UHR,
      FES, and ChSz control groups, respectively) underwent (1)H MRS in a 3-Tesla
      scanner to examine metabolites in medial prefrontal cortex. The analysis revealed
      significant decreases in the medial prefrontal NAA and glutamate + glutamine
      (Glx) levels, specifically in the ChSz group as indexed by a significant
      interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls)
      (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with
      the other metabolites in the patients with ChSz was also supported by a
      significant interaction between the clinical status and types of metabolites that
      only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present
      study demonstrates significant differences in (1)H MRS abnormalities at different
      stages of schizophrenia, which potentially correspond to changes in glutamatergic
      neurotransmission, plasticity, and/or excitotoxicity and regional neuronal
      integrity with relevance for the progression of schizophrenia. 

PMID- 24023253
TI  - A role for prohibitin in mast cell activation: location matters.
AB  - Prohibitin 1 (PHB1) and PHB2 are evolutionarily conserved, ubiquitously
      expressed, pleotropic proteins that control various fundamental cellular
      processes, including proliferation, migration, metabolism, and death. Studies
      have unveiled a crucial role for plasma membrane-associated PHBs in regulating
      tumor metastasis, viral entry, and immune cell activation. A study now identifies
      a role for PHB1 in the activation of mast cells and allergic reactions mediated
      by immunoglobulin E (IgE). PHB1 was primarily localized in mast cell granules;
      however, in response to stimulation with antigen, PHB1 translocated to plasma
      membrane lipid rafts to form a ternary complex with the high-affinity IgE
      receptor FcepsilonRIgamma and the nonreceptor tyrosine kinase Syk. Syk became
      activated, which led to the activation of downstream signaling that stimulated
      mast cell degranulation and the secretion of cytokines. PHB1 was phosphorylated
      by the Src family tyrosine kinase Lyn, and palmitoylation of PHB1 was required
      for its association with the plasma membrane. These observations unveil a
      previously uncharacterized facet of prohibitin biology and shed further light on
      the proximal events that drive the activation of FcepsilonRI by IgE in mast cells
      during allergic reactions. 

PMID- 24023254
TI  - The scaffold protein prohibitin is required for antigen-stimulated signaling in
      mast cells.
AB  - The protein prohibitin (PHB) is implicated in diverse cellular processes,
      including cell signaling, transcriptional control, and mitochondrial function. We
      found that PHB was abundant in the intracellular granules of mast cells, which
      are critical for allergic responses to antigens. Thus, we investigated whether
      PHB played a role in signaling mediated by the high-affinity receptor for antigen
      bound immunoglobulin E (IgE), FcepsilonRI. PHB-specific small interfering RNAs
      (siRNAs) inhibited antigen-mediated signaling, degranulation, and cytokine
      secretion by mast cells in vitro. Knockdown of PHB inhibited the antigen
      dependent association of the tyrosine kinase Syk with FcepsilonRI and inhibited
      the activation of Syk. Fractionation studies revealed that PHB translocated from
      intracellular granules to plasma membrane lipid rafts in response to antigen, and
      knockdown of PHB suppressed the movement of FcepsilonRIgamma and Syk into lipid
      rafts. Tyrosine phosphorylation of PHB by Lyn was observed early after exposure
      to antigen, and point mutations in PHB indicated that Tyr(114) and Tyr(259) were
      required for the recruitment of Syk to FcepsilonRIgamma and mast cell activation.
      In mice, PHB-specific siRNAs inhibited antigen-initiated mast cell degranulation,
      passive cutaneous anaphylaxis, and passive systemic anaphylaxis. Together, these
      results suggest that PHB is essential for FcepsilonRI-mediated mast cell
      activation and allergic responses in vivo, raising the possibility that PHB might
      serve as a therapeutic target for the treatment of allergic diseases. 

PMID- 24023255
TI  - Ajuba family proteins link JNK to Hippo signaling.
AB  - Wounding, apoptosis, or infection can trigger a proliferative response in
      neighboring cells to replace damaged tissue. Studies in Drosophila have
      implicated c-Jun amino-terminal kinase (JNK)-dependent activation of Yorkie (Yki)
      as essential to regeneration-associated growth, as well as growth associated with
      neoplastic tumors. Yki is a transcriptional coactivator that is inhibited by
      Hippo signaling, a conserved pathway that regulates growth. We identified a
      conserved mechanism by which JNK regulated Hippo signaling. Genetic studies in
      Drosophila identified Jub (also known as Ajuba LIM protein) as required for JNK
      mediated activation of Yki and showed that Jub contributed to wing regeneration
      after wounding and to tumor growth. Biochemical studies revealed that JNK
      promoted the phosphorylation of Ajuba family proteins in both Drosophila and
      mammalian cells. Binding studies in mammalian cells indicated that JNK increased
      binding between the Ajuba family proteins LIMD1 or WTIP and LATS1, a kinase
      within the Hippo pathway that inhibits the Yki homolog YAP. Moreover, JNK
      promoted binding of LIMD1 and LATS1 through direct phosphorylation of LIMD1.
      These results identify Ajuba family proteins as a conserved link between JNK and
      Hippo signaling, and imply that JNK increases Yki and YAP activity by promoting
      the binding of Ajuba family proteins to Warts and LATS. 

PMID- 24023256
TI  - Timing, adherence, resistance, and ... persistence? new insight into the
      mechanisms of failure of HIV type 1 postexposure prophylaxis.

PMID- 24023257
TI  - Molecular mechanisms of HIV type 1 prophylaxis failure revealed by single-genome
      sequencing.
AB  - Trials of human immunodeficiency virus type 1 (HIV) pre- and postexposure
      prophylaxis show promise. Here, we describe a novel strategy for deciphering
      mechanisms of prophylaxis failure that could improve therapeutic outcomes. A
      healthcare worker began antiretroviral prophylaxis immediately after a high-risk
      needlestick injury but nonetheless became viremic 11 weeks later. Single-genome
      sequencing of plasma viral RNA identified 15 drug susceptible transmitted/founder
      HIV genomes responsible for productive infection. Sequences emanating from these
      genomes exhibited extremely low diversity, suggesting virus sequestration as
      opposed to low-level replication as the cause of breakthrough infection.
      Identification of transmitted/founder viruses allows for genome-wide assessment
      of molecular mechanisms of prophylaxis failure. 

PMID- 24023258
TI  - Dentition, bone loss, and the aging of the mandible.
AB  - BACKGROUND: Facial aging is a dynamic process with impact on both the soft
      tissues and the bones. Despite a growing body of evidence, controversy still
      exists regarding absolute characteristics of the aging facial skeleton.
      OBJECTIVE: The purpose of this study was to investigate various mandibular
      measurements in different age groups and to delineate the relation of the
      dentition to these parameters. METHODS: Ninety Caucasian mandibles were assessed
      for the following distance landmarks: gonion-gonion, infradentale-gnathion,
      mental foramen-mandibular crest, mental foramen-inferior mandibular border,
      gnathion-gonion, condyle-gonion, and gonial angle. The measurements were compared
      according to age, sex, and dentition. RESULTS: The number of teeth decreased
      significantly with increasing age in males (P = .002) and females (P < .001).
      There were no other statistically significant differences between age groups for
      the rest of the parameters. The infradentale-gnathion distance (P = .005) and the
      mental foramen-mandibular crest distance (P < .001) was found to increase with
      total number of teeth. Other parameters did not show a significant relation to
      dentition. All parameters were significantly larger in the male subgroups with
      the exception of gnathion-gonion distance and gonial angle. Bilateral mandibular
      measurements were symmetric except for the gonial angle, which was more obtuse on
      the right side in males (P = .007) and females (P = .018). CONCLUSIONS: Our
      findings support previous evidence that dentition is the main determinant of the
      morphology of the mandible. The skeletal characteristics are variable among
      individuals, and a longitudinal study is required to better understand age
      related changes of the mandible.

PMID- 24023259
TI  - beta-catenin mediates tumor-induced immunosuppression by inhibiting cross-priming
      of CD8+ T cells.
AB  - Whereas CD8+ T cells are essential for anti-tumor immunity, tumors often evade
      CD8+ T cell surveillance by immunosuppression. As the initiators of antigen
      specific immune responses, DCs are likely to play a central role in regulating
      the balance between immunity and tolerance to tumor antigens and are specialized
      in their ability to cross-present exogenous tumor antigens on MHC class I
      molecules to initiate CD8+ T cell immunity. However, it remains unclear whether
      and how tumors modulate DC functions to suppress CD8+ T cell responses. We have
      shown previously that beta-catenin signaling in DCs promotes DC-mediated CD8+ T
      cell tolerance. Here, we tested the hypothesis that beta-catenin in DCs mediates
      tumor-induced suppression of CD8+ T cell immunity by inhibiting the ability of
      DCs in cross-priming. beta-Catenin was activated in DCs by multiple tumors in
      vivo and in vitro. B16 melanoma-bearing mice, when vaccinated with DC-targeting
      anti-DEC-205 mAb fused with tumor antigens, exhibited dampened CD8+ immunity,
      similar to DC-beta-catenin(active) mice. DCs from DC-beta-catenin(active) and
      tumor-bearing mice were deficient in cross-priming, and antigen-specific CD8+ T
      cells primed in these mice resulted in dampened CD8+ memory responses.
      Importantly, DC-beta-catenin-/- mice completely abrogate tumor-mediated
      inhibition of cross-priming, suggesting that tumor-induced inhibition of cross
      priming is dependent on beta-catenin. Finally, enhancing cross-priming at the
      priming or recall phase rescued beta-catenin-suppressed CD8+ immunity in DC-beta
      catenin(active) and tumor-bearing mice. Thus, beta-catenin-mediated inhibition of
      cross-priming represents a new and potentially general mechanism that tumors
      employ to achieve immunosuppression.

PMID- 24023260
TI  - Genetic association with lipids in Filipinos: waist circumference modifies an
      APOA5 effect on triglyceride levels.
AB  - Blood levels of lipoprotein cholesterol and triglycerides (TGs) are highly
      heritable and are major risk factors for cardiovascular disease (CVD).
      Approximately 100 lipid-associated loci have been identified in populations of
      European ancestry. We performed a genome-wide association study of lipid traits
      in 1,782 Filipino women from the Cebu Longitudinal Health and Nutrition Survey,
      and tested for evidence of interactions with waist circumference. We conducted
      additional association and interaction analyses in 1,719 of their young adult
      offspring. Genome-wide significant associations (P < 5 * 10-8) were detected at
      APOE for low density lipoprotein cholesterol and total cholesterol, and at APOA5
      for TGs. Suggestive associations (P < 10-6) were detected at GCKR for TGs, and at
      CETP and TOM1 for high density lipoprotein cholesterol. Our data also supported
      the existence of allelic heterogeneity at APOA5, CETP, LIPC, and APOE. The
      secondary signal (Gly185Cys) at APOA5 exhibited a single nucleotide polymorphism
      (SNP)-by-waist circumference interaction affecting TGs (Pinteraction = 1.6 * 10
      4), manifested by stronger SNP effects as waist circumference increased. These
      findings provide the first evidence that central obesity may accentuate the
      effect of the TG-increasing allele of the APOA5 signal, emphasizing that CVD risk
      could be reduced by central obesity control.

PMID- 24023261
TI  - THOC5: a novel gene involved in HDL-cholesterol metabolism.
AB  - Although numerous genes are known to regulate serum lipid traits, identified
      variants explain only a small proportion of the expected heritability. We
      intended to identify further genetic variants associated with lipid phenotypes in
      a self-contained population of Sorbs in Germany. We performed a genome-wide
      association study (GWAS) on LDL-cholesterol, HDL-cholesterol (HDL-C), and
      triglyceride (TG) levels in 839 Sorbs. All single-nucleotide polymorphisms with a
      P value <0.01 were subjected to a meta-analysis, including an independent Swedish
      cohort (Diabetes Genetics Initiative; n = ~3,100). Novel association signals with
      the strongest effects were subjected to replication studies in an additional
      German cohort (Berlin, n = 2,031). In the initial GWAS in the Sorbs, we
      identified 14 loci associated with lipid phenotypes reaching P values <10-5 and
      confirmed significant effects for 18 previously reported loci. The combined meta
      analysis of the three study cohorts (n(HDL) = 6041; n(LDL) = 5,995; n(TG) =
      6,087) revealed a novel association for a variant in THOC5 (rs8135828) with serum
      HDL-C levels (P = 1.78 * 10-7; Z-score = -5.221). Consistently, the variant was
      also associated with circulating APOA1 levels in Sorbs. The small interfering RNA
      mediated mRNA silencing of THOC5 in HepG2 cells resulted in lower mRNA levels of
      APOA1, SCARB1, and ABCG8 (all P < 0.05). We propose THOC5 to be a novel gene
      involved in the regulation of serum HDL-C levels.

PMID- 24023262
TI  - Recent advances in palliative cancer care at a regional hospital in Japan.
AB  - More than 30 years have passed since the introduction of the concept of
      palliative care in cancer care in Japan. However, the majority of the estimated
      three million cancer patients in Japan do not receive palliative care. Higashi
      Sapporo Hospital was established in 1983 as a hospital specialized in cancer
      care. The palliative care unit of our hospital currently consists of 58 beds. Our
      hospital is one of the largest hospitals in Japan in terms of the number of
      palliative care beds. On admission to our hospital, all patients are evaluated
      for palliative care by a multi-disciplinary team and some patients who undergo
      anticancer therapy receive palliative care when necessary. There are about 65
      patients on average (28.3%) who are receiving only palliative care. In 2011, 793
      patients died of cancer while admitted at our hospital. This number of cancer
      deaths accounted for 15% of the 5,324 cancer deaths in Sapporo City in the same
      year. Our hospital has played an active role according to the philosophy that
      "palliative cancer care is part of cancer medical care". We here report the
      current status of the contribution of our hospital to overcoming problems in
      palliative care and cancer care in Japan. 

PMID- 24023263
TI  - The experiences of stress of palliative care providers in Malaysia: a thematic
      analysis.
AB  - A qualitative study was conducted with semistructured interviews to explore the
      experiences of stress in 20 palliative care providers of University Malaya
      Medical Centre in Malaysia. The results were thematically analyzed. Nine basic
      themes were generated: (1) organizational challenges, (2) care overload, (3)
      communication challenges, (4) differences in opinion, (5) misperceptions and
      misconceptions, (6) personal expectations, (7) emotional involvement, (8) death
      and dying thoughts, and (9) appraisal and coping. A total care model of
      occupational stress in palliative care was conceptualized from the analysis. This
      model may inform the development of interventions in the prevention and
      management of stress in palliative care. 

PMID- 24023264
TI  - The Ligurian high-school educational project on palliative care: development and
      piloting of a school-based intervention on bereavement and severe illness.
AB  - This study was aimed at developing and piloting a school-based intervention on
      severe illness-induced bereavement through a project focused on spreading
      knowledge of palliative care among high school students (phases 0-II Medical
      Research Council Framework). The intervention entailed the screening of a topic
      related movie and a classroom meeting. Eight classes from 2 high schools
      participated, and a before-after evaluation was used to assess intervention
      feasibility and impact. Valid questionnaires, including 2 open-ended questions
      focusing on bereavement and strategies for coping with loss, were filled in by
      89% (before) and 84% (after) of the 159 students. In the after evaluation,
      content analysis on the "strategies" question showed that answers concerning
      closeness and sharing were reported more frequently. Positive feedback was
      collected as regards the overall experience. 

PMID- 24023265
TI  - Petroleum jelly (vaseline balls) for the treatment of constipation: a survey of
      hospice and palliative care practitioners.
AB  - Constipation is a common symptom at end of life, impacting patient outcomes and
      healthcare costs. Hospice and palliative care professionals often use practices
      based on anecdotal evidence. One such intervention is an oral preparation of
      petroleum jelly (OPJ), referred to as "Vaseline balls." This survey was designed
      to collect information regarding healthcare practitioners' knowledge and
      attitudes toward the use of OPJ for the management of constipation in hospice and
      palliative care. An online survey was distributed to physicians, nurse
      practitioners, nurses, and pharmacists who work with hospice and palliative care
      patients. A total of 67% (n=237/353) of responders reported being familiar with
      the use of OPJ. Results indicate there is a need for further clinical research on
      the use of OPJ to guide practice. 

PMID- 24023266
TI  - Lack of impact of cytotoxic T-lymphocyte antigen 4 gene exon 1 polymorphism on
      susceptibility to or clinical course of egyptian childhood immune
      thrombocytopenic purpura.
AB  - Dysfunctional T-lymphocyte immunity plays an important role in the
      pathophysiology of immune thrombocytopenic purpura (ITP). Cytotoxic T-lymphocyte
      antigen 4 (CTLA-4)-a surface marker expressed on T regulatory cells and activated
      T lymphocytes-is a negative modulator of T-cell responses. Polymorphisms of the
      CTLA-4 may alter the level of antigen expression and hence may influence immune
      regulation. The study aimed to evaluate the possible contribution of CTLA-4 exon
      1 49 A>G polymorphism to the pathogenesis of ITP and its relation to age of
      disease onset, clinical course, and response to therapy. Genotyping of CTLA-4
      exon 1 49 A>G was performed in 100 pediatric patients with ITP and 259 healthy
      individuals by polymerase chain reaction-restricted fragment length polymorphism.
      No significant differences existed in genotype or allele distributions between
      patients and controls for the studied polymorphism. Comparable genotypes and
      allele frequencies were obtained between the 2 groups after their stratification
      by age of disease onset, clinical course, or response to therapy. In conclusion,
      CTLA-4 exon 1 49 A>G polymorphism is not associated with susceptibility to ITP in
      the Egyptian population; neither it affects the clinical picture of the disease. 

PMID- 24023267
TI  - Evaluation factors of pulmonary embolism severity and prognosis.
AB  - Management of pulmonary embolism (PE) is still unclear. We summarized 16 kinds of
      evaluation factors of PE severity and prognosis, and we analyzed the single and
      joint value for short-term and long-term prognosis. Among them, biomarkers such
      as brain natriuretic peptide or N-terminal probrain natriuretic peptide,
      troponin, and heart-type fatty acid-binding protein are the best indicators of PE
      severity and short-term prognosis. They might replace imaging detections in
      evaluating PE severity. But the positive predictive value of all the biomarkers
      is low, and we need to improve each value through joint detection. The PE
      severity index and simplified PE severity index are more suitable for evaluating
      the overall risk and long-term prognosis. They could be used as complements of
      indicators of the PE severity, especially in identifying low-risk group.
      Integrated risk stratification and strategies of management should be established
      based on the 2 aspects mentioned previously. 

PMID- 24023268
TI  - Aromatase activity induction in human adipose fibroblasts by retinoic acids via
      retinoic acid receptor alpha.
AB  - Estrogen synthesis in adipose tissue is associated with the development of breast
      cancer. Tumors are preferentially found in breast quadrants with strongest
      expression of the cytochrome P450 aromatase (encoded by the gene CYP19A1).
      Several promoters regulated by various hormonal factors drive aromatase
      expression in human breast adipose fibroblasts (BAFs). As adipose tissue is a
      major source of retinoids, in this study, we investigated their role in the
      regulation of aromatase expression. The retinoids all-trans-retinoic acid (at-RA)
      and 9-cis-RA induce aromatase activity in human BAFs. In BAFs, at-RA induces
      aromatase gene expression via promoter I.4. In 3T3-L1 cells, both retinoids
      specifically drive luciferase reporter gene expression under the control of
      aromatase promoter I.4, whereas other promoters active in human adipose tissue
      are insensitive. Activation by retinoids depends on a 467 bp fragment (-256/+211)
      of promoter I.4 containing four putative retinoic acid response elements (RAREs).
      Site-directed mutagenesis revealed that only RARE2 (+91/+105) mediates the
      retinoid-dependent induction of reporter gene activity. In 3T3-L1 preadipocytes
      and human BAFs, RA receptor alpha (RARalpha (RARA)) expression is predominant,
      whereas RARbeta (RARB) or RARgamma (RARG) expression is low. Electrophoretic
      mobility shift assays with nuclear extracts obtained from human BAFs and 3T3-L1
      cells identified a specific RARE2-binding complex. Retinoids enhanced complex
      formation, whereas pre-incubation with anti-RARalpha antibodies prohibited the
      binding of RARalpha to RARE2. Chromatin immunoprecipitation showed RA-dependent
      binding of RARalpha to the RARE2-containing promoter region in vivo. Furthermore,
      we provide evidence that RARE2 is also necessary for the basal activation of
      promoter I.4 in these cells. Taken together, these findings indicate a novel
      retinoid-dependent mechanism of aromatase activity induction in adipose tissue. 

PMID- 24023269
TI  - Extrastriatal dopaminergic changes in Parkinson's disease patients with impulse
      control disorders.
AB  - OBJECTIVE: To investigate the extrastriatal dopaminergic neural changes in
      relation to the medication-related impulse control disorders (ICD) in Parkinson's
      disease (PD). METHOD: A total of 31 subjects (11 and 11 drug-treated PD patients
      with and without medication-related ICDs and 9 healthy controls) having no other
      co-morbid psychiatric disorders participated in this study. Each subject
      underwent dynamic N-(3-[(18)F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)
      nortropane (FP-CIT) positron emission tomography scans. Binding potentials (BP)
      at nucleus accumbens, amygdala, orbitofrontal and ventromedial prefrontal cortex
      (VMPFC), putamen and caudate nucleus were estimated, and whole brain parametric
      maps of [(18)F]-FP-CIT binding were analysed by original and putaminal normalised
      manners. RESULTS: Compared with the healthy controls, BPs at both VMPFCs were
      significantly high and the extrastriatal to putaminal BP ratios at all regions
      were approximately three times higher in both PD groups. The PD ICD patients
      showed significantly higher BPs at the right VMPFC and tendency to lower BPs at
      the left nucleus accumbens compared with those free of ICD. The ICD subjects also
      showed reduced uptakes at both ventral striatal regions in the original
      parametric analysis and higher uptakes at the left insular and right posterior
      cingulate cortex and lower uptakes at both ventral pallidums in the putaminal
      normalised parametric analysis compared with the non-ICD subjects. CONCLUSIONS: A
      great gap in extrastriatal versus striatal dopaminergic fibre degenerations is an
      intrinsic condition predisposing to ICD in PD. Distinct pattern of extrastriatal
      changes between the ICD and non-ICD patients could provide a further insight into
      a mechanism of ICD in PD.

PMID- 24023270
TI  - Changes in pathological and biochemical findings of systemic tissue sites in
      familial amyloid polyneuropathy more than 10 years after liver transplantation.
AB  - OBJECTIVE: To elucidate the long-term effects of liver transplantation (LT) on
      familial amyloid polyneuropathy (FAP). METHODS: We investigated
      clinicopathological and biochemical characteristics of systemic tissues in four
      autopsied cases of FAP patients surviving more than 10 years after LT and seven
      autopsied cases without LT. For analysing the truncated form of transthyretin
      (TTR) in amyloid, we also employed specimens from additional 18 FAP patients.
      RESULTS: Several tissue sites such as the heart, tongue and spinal cord had
      moderate-to-severe amyloid deposits but other tissues showed no or mild amyloid
      deposition. Those findings seemed similar to those observed in senile systemic
      amyloidosis (SSA), a sporadic amyloidosis caused by wild-type (WT) TTR. Also,
      amyloid deposits in systemic tissue sites except for the spinal cord in patients
      after LT derived mostly from WT TTR secreted from the normal liver grafts. In
      addition, in non-transplantation patients, proportions of WT TTR seemed to be
      relatively high in those tissue sites in which patients after LT had severe
      amyloid deposition, which suggests that WT TTR tends to form amyloid in those
      tissue sites. Finally, although the truncation of TTR in amyloid deposits did not
      depend on undergoing LT, we elucidated the truncation of TTR occurred
      predominantly in patients from non-endemic areas of Japan, where FAP
      amyloidogenic TTR V30M patients are late onset and low penetrance, compared with
      patients from an endemic area of Japan. CONCLUSIONS: FAP may shift to systemic WT
      TTR amyloid formation after LT, which seems to be similar to the process in SSA.
      The truncation of TTR in amyloid deposits may depend on some genetic or
      environmental factors other than undergoing LT.

PMID- 24023272
TI  - Comparing the effect of the interaction between fine and coarse scales and
      surround suppression on motion discrimination.
AB  - Our ability to discriminate motion direction in a Gabor patch diminishes with
      increasing size and contrast, indicating surround suppression. Discrimination is
      also impaired by a static low-spatial-frequency patch added to the moving
      stimulus, suggesting an antagonism between sensors tuned to fine and coarse
      features. Using Bayesian staircases, we measured duration thresholds in motion
      direction discrimination tasks using vertically oriented Gabor patches moving at
      2 degrees /s. In two experiments, we tested two contrasts (2.8% and 46%), five
      window sizes (from 0.7 degrees  to 5 degrees ), and two spatial frequencies (1
      c/deg and 3 c/deg), either presented alone or added to a static pattern. When the
      moving pattern was presented alone, duration thresholds increased with size at
      high contrast and decreased with size at low contrast. At low contrast, when a
      static pattern of 3 c/deg was added to a moving pattern of 1 c/deg, duration
      thresholds were similar to the case when the moving pattern was presented alone;
      however, at high contrast, duration thresholds were facilitated, eliminating the
      effect of surround suppression. When a static pattern of 1 c/deg was added to a
      moving pattern of 3 c/deg, duration thresholds increased about 4 times for high
      contrast and 2 times for low contrast. These results show that the antagonism
      between sensors tuned to fine and coarse scales is more complex than surround
      suppression, suggesting that it reflects the operation of a different mechanism. 

PMID- 24023271
TI  - Do community-based patient assistance programs affect the treatment and well
      being of patients with breast cancer?
AB  - PURPOSE: Patients with breast cancer who need adjuvant treatments often fail to
      receive them. High-quality, community-based patient-assistance programs are an
      underused, inexpensive resource to help patients with cancer obtain needed
      therapy. We sought to determine whether connecting women to patient-assistance
      programs would reduce underuse of adjuvant therapies. METHODS: We conducted a
      randomized trial of 374 women (190 assigned intervention [INT], 184 to usual care
      [UC]) with early-stage breast cancer who underwent surgery between October 2006
      and August 2009. After initial needs assessment, individualized action plans were
      created to connect INT patients with targeted patient-assistance programs; UC
      patients received an informational pamphlet. Main outcome measures were receiving
      adjuvant treatment and obtaining help. RESULTS: High rates of INT and UC patients
      received treatment: 87% INT versus 91% UC women who underwent lumpectomy received
      radiotherapy (P = .39); 93% INT versus 86% UC women with estrogen receptor (ER) 
      negative tumors >= 1 cm received chemotherapy (P = .42); 92% INT versus 93% UC
      women with ER-positive tumors >= 1 cm received hormonal therapy (P = .80). Many
      women reported needs: 63% had informational; 55%, psychosocial; and 53%,
      practical needs. High rates of INT patients with needs connected with a program
      within 2 weeks (92%). At 6 months, INT and UC women used patient-assistance
      programs at similar rates (75% v 76%; P = .54). Women with informational or
      psychosocial needs were more likely to receive help (relative risk [RR], 1.77;
      95% CI, 1.51 to 1.90 and RR, 1.37; 95% CI, 1.06 to 1.61, respectively).
      CONCLUSION: INT and UC patients received high rates of adjuvant treatment
      regardless of trial assignment. Patients with breast cancer who connect to
      relevant patient assistance programs receive useful informational and
      psychosocial but not practical help.

PMID- 24023273
TI  - An objective signature for visual binding of face parts in the human brain.
AB  - Whether and how the parts of a visual object are grouped together to form an
      integrated ("holistic") representation is a central question in cognitive
      neuroscience. Although the face is considered to be the quintessential example of
      holistic representation, this issue has been the subject of much debate in face
      perception research. The implication of holistic processing is that the response
      to the whole cannot be predicted from the sum of responses to the parts. Here we
      apply techniques from nonlinear systems analysis to provide an objective measure
      of the nonlinear integration of parts into a whole, using the left and right
      halves of a face stimulus as the parts. High-density electroencephalogram (EEG)
      was recorded in 15 human participants presented with two halves of a face
      stimulus, flickering at different frequencies (5.88 vs. 7.14 Hz). Besides
      specific responses at these fundamental frequencies, reflecting part-based
      responses, we found intermodulation components (e.g., 7.14 - 5.88 = 1.26 Hz) over
      the right occipito-temporal hemisphere, reflecting nonlinear integration of the
      face halves. Part-based responses did not depend on the relative alignment of the
      two face halves, their spatial separation, or whether the face was presented
      upright or inverted. By contrast, intermodulations were virtually absent when the
      two halves were spatially misaligned and separated. Inversion of the whole face
      configuration also reduced specifically the intermodulation components over the
      right occipito-temporal cortex. These observations indicate that the
      intermodulation components constitute an objective, configuration-specific
      signature of an emergent neural representation of the whole face that is distinct
      from that generated by the parts themselves. 

PMID- 24023274
TI  - Depth perception in the framework of General Object Constancy.
AB  - Size constancy is a well-known example of perceptual stabilization accounting for
      the effect of viewing distance on retinal image size. In a recent study (Qian &
      Petrov, 2012), we demonstrated a similar stabilization mechanism for contrast
      perception and suggested that the brain accounts for effects of perceived
      distance on various other object features in a similar way, a hypothesis that we
      called General Object Constancy. Here we report a new illusion of depth further
      supporting this hypothesis. Pairs of disks moved across the screen in a pattern
      of radial optic flow. A pair comprised a small black disk floating in front of a
      large white disk, creating the percept of a pencil tip viewed head on. As these
      "pencils" moved away, they appeared to grow in contrast, in diameter, and also
      appeared to be getting "sharper." The contrast and size illusions replicated our
      previous findings, while the depth gradient (sharpness) illusion revealed a depth
      constancy phenomenon. We discovered that depth and size constancies were related,
      e.g., the two illusions were strongly correlated across observers. Whereas the
      illusory diameter increase could not be canceled by any degree of depth
      modulation, decreasing the diameter of the "pencils" during optic flow motion
      (thus increasing their disparity gradient) weakened the illusory depth gradient
      increase. This paradoxical result, as well as our other results, is explained by
      the General Object Constancy model: Besides using the same scaling factor to
      account for size, contrast, and depth variations with distance, the brain uses
      the apparent object size to additionally scale contrast and depth signals. 

PMID- 24023275
TI  - Effects of surface reflectance and 3D shape on perceived rotation axis.
AB  - Surface specularity distorts the optic flow generated by a moving object in a way
      that provides important cues for identifying surface material properties
      (Doerschner, Fleming et al., 2011). Here we show that specular flow can also
      affect the perceived rotation axis of objects. In three experiments, we
      investigate how three-dimensional shape and surface material interact to affect
      the perceived rotation axis of unfamiliar irregularly shaped and isotropic
      objects. We analyze observers' patterns of errors in a rotation axis estimation
      task under four surface material conditions: shiny, matte textured, matte
      untextured, and silhouette. In addition to the expected large perceptual errors
      in the silhouette condition, we find that the patterns of errors for the other
      three material conditions differ from each other and across shape category,
      yielding the largest differences in error magnitude between shiny and matte,
      textured isotropic objects. Rotation axis estimation is a crucial implicit
      computational step to perceive structure from motion; therefore, we test whether
      a structure from a motion-based model can predict the perceived rotation axis for
      shiny and matte, textured objects. Our model's predictions closely follow
      observers' data, even yielding the same reflectance-specific perceptual errors.
      Unlike previous work (Caudek & Domini, 1998), our model does not rely on the
      assumption of affine image transformations; however, a limitation of our approach
      is its reliance on projected correspondence, thus having difficulty in accounting
      for the perceived rotation axis of smooth shaded objects and silhouettes. In
      general, our findings are in line with earlier research that demonstrated that
      shape from motion can be extracted based on several different types of optical
      deformation (Koenderink & Van Doorn, 1976; Norman & Todd, 1994; Norman, Todd, &
      Orban, 2004; Pollick, Nishida, Koike, & Kawato, 1994; Todd, 1985).

PMID- 24023276
TI  - Orientation is different: Interaction between contour integration and feature
      contrasts in visual search.
AB  - Salient items usually capture attention and are beneficial to visual search.
      Jingling and Tseng (2013), nevertheless, have discovered that a salient collinear
      column can impair local visual search. The display used in that study had 21 rows
      and 27 columns of bars, all uniformly horizontal (or vertical) except for one
      column of bars orthogonally oriented to all other bars, making this unique column
      of collinear (or noncollinear) bars salient in the display. Observers
      discriminated an oblique target bar superimposed on one of the bars either in the
      salient column or in the background. Interestingly, responses were slower for a
      target in a salient collinear column than in the background. This opens a
      theoretical question of how contour integration interacts with salience
      computation, which is addressed here by an examination of how salience modulated
      the search impairment from the collinear column. We show that the collinear
      column needs to have a high orientation contrast with its neighbors to exert
      search interference. A collinear column of high contrast in color or luminance
      did not produce the same impairment. Our results show that orientation-defined
      salience interacted with collinear contour differently from other feature
      dimensions, which is consistent with the neuronal properties in V1.

PMID- 24023277
TI  - Choice of saccade endpoint under risk.
AB  - Eye movements function to bring detailed information onto the high-resolution
      region of the retina. Previous research has shown that human observers select
      fixation points that maximize information acquisition and minimize target
      location uncertainty. In this study, we ask whether human observers choose the
      saccade endpoint that maximizes gain when there are explicit rewards associated
      with correctly detecting the target. Observers performed an 8-alternative forced
      choice detection task for a contrast-defined target in noise. After a single
      saccade, observers indicated the target location. Each potential target location
      had an associated reward that was known to the observer. In some conditions, the
      reward at one location was higher than at the other locations. We compared human
      saccade endpoints to those of an ideal observer that maximizes expected gain
      given the respective human observer's visibility map, i.e., d' for target
      detection as a function of retinal location. Varying the location of the highest
      reward had a significant effect on human observers' distribution of saccade
      endpoints. Both human and ideal observers show a high density of saccades made
      toward the highest rewarded and actual target locations. But humans' overall
      spatial distributions of saccade endpoints differed significantly from the ideal
      observer as they made a greater number of saccade to locations far from the
      highest rewarded and actual target locations. Suboptimal choice of saccade
      endpoint, possibly in combination with suboptimal integration of information
      across saccades, had a significant effect on human observers' ability to
      correctly detect the target and maximize gain.

PMID- 24023278
TI  - Ubiquitination and the ubiquitin - proteasome system in the pathogenesis and
      treatment of squamous head and neck carcinoma.
AB  - Squamous carcinomas of the head and neck area are carcinomas that were
      traditionally associated with alcohol and tobacco abuse. More recently, a
      pathogenic relationship of oncogenic human papilloma viruses (HPV) with head and
      neck cancer of the oropharynx and the base of the tongue has been revealed. Two
      proteins of HPV, E6 and E7, are involved in neoplastic transformation not only in
      the head and neck but in other locations, where these epitheliotropic viruses
      cause carcinomas, such as the uterine cervix and the anal region. The E6 viral
      protein associates with cellular E3 ubiquitin ligase E6-AP and promotes
      degradation of tumour suppressor p53 by the proteasome. This molecular event
      reveals the important role that the ubiquitin-proteasome system (UPS) plays in
      the pathogenesis of head and neck cancer. The role of this system in head and
      neck carcinogenesis is not restricted to the destruction of p53 but extends to
      most, if not all, signaling pathways that regulate carcinogenesis in this
      location. These roles are reviewed here and implications for treatment are
      discussed. 

PMID- 24023279
TI  - Mitochondrial DNA damage is uncommon in cancer but can promote aggressive
      behaviour.
AB  - The mitochondrial genome (mtDNA) has been implicated in carcinogenesis. It is
      more susceptible than nuclear DNA to damage from reactive oxygen species and
      mutagens, and has a limited DNA repair machinery. Studies of human cancer have
      shown that a small proportion of tumours carry significant mtDNA mutations but
      methodological flaws undermine some of these findings. Mutations in mtDNA are
      often associated with elevated levels of reactive oxygen species and
      stabilisation of Hypoxia-Inducible Factor-1 (HIF1), but it has not been clearly
      demonstrated that these relationships are causal. Some mutations in the coding
      region of mtDNA can confer increased tumourigenicity, motility and metastasis on
      cells in vitro and in vivo but these mutations are only rarely found in ex vivo
      samples. Mitochondrial DNA does not play a major role in common types of cancer,
      but may promote aggressive behaviour in some cases. Shortcomings in mtDNA repair
      mechanisms could be exploited to promote apoptosis of tumour cells. 

PMID- 24023280
TI  - The value of pemetrexed for the treatment of malignant pleural mesothelioma: a
      comprehensive review.
AB  - This review aims to provide insight into treatment of malignant pleural
      mesothelioma (MPM) considering effects on survival, quality of life (QoL) and
      costs, in order to determine the value of pemetrexed in MPM treatment. Cisplatin
      in combination with pemetrexed or raltitrexed increased survival in MPM, whereas
      vinorelbine and gemcitabine have led to good response rates. None of these appear
      to have any detrimental effect with respect to symptoms and global QoL. The cost
      effectiveness of pemetrexed-cisplatin was found to be acceptable in advanced MPM
      compared with cisplatin, but raltitrexed-cisplatin was found to be a more cost
      effective treatment option. This may also apply for gemcitabine and vinorelbine,
      since in contrast to pemetrexed, both agents can be obtained from generic
      manufacturers. As yet platinum-doublet therapy is the most effective palliative
      treatment of MPM. To provide a more cost-effective treatment approach for
      advanced MPM, further research should include randomized controlled trials
      comparing the recommended pemetrexed-cisplatin directly with platinum doublets
      with raltitrexed, gemcitabine, or vinorelbine. 

PMID- 24023281
TI  - APO010, a synthetic hexameric CD95 ligand, induces death of human glioblastoma
      stem-like cells.
AB  - The treatment of glioblastoma remains a major challenge in the field of neuro
      oncology. There is emerging evidence that glioblastomas consist of heterogeneous
      cell populations with a small subset of cells with stem cell-like properties
      which might be resistant to conventional therapy and are thus crucial for tumor
      recurrence. These glioma-initiating cells (GICs) are therefore an attractive
      therapeutic target. Death receptor activation is one promising approach of cancer
      therapy. The synthetic hexameric cluster of differentiation 95 (CD95) agonist
      APO010 exhibits strong antiglioma activity towards human glioma cell lines, as
      well as in cell cultures of primary glioblastoma. Here, we investigated the
      ability of APO010 to induce cell death in a panel of previously well-defined GIC
      lines. The GIC lines and their derived differentiated cultures expressed CD95 on
      the cell surface and were sensitive towards APO010-mediated cell death to a
      variable extent. Temozolomide enhanced sensitivity of GICs to APO010. APO010
      warrants being further evaluated as a tool to target GICs. 

PMID- 24023282
TI  - Targeting ovarian cancer and chemoresistance through selective inhibition of
      sphingosine kinase-2 with ABC294640.
AB  - ABC294640, a selective inhibitor of sphingosine kinase-2, inhibits the formation
      of sphingosine 1-phosphate (S1P), a signaling lipid implicated in promoting tumor
      survival. We investigated the anticancer activity of ABC294640 in two ovarian
      cancer cell lines, BG-1 and Caov-3. ABC294640 dose-dependently inhibited
      clonogenic survival and cell viability of both ovarian cancer lines in vitro.
      Using enzyme-linked immunosorbant assays and western blot detection in
      chemoresistant Caov-3 cells, treatment with ABC294640 alone also potentiated bcl
      2-associated X-protein and caspase-9 transcription levels, although it did not
      significantly increase apoptotic cell death. Interestingly, ABC294640
      administered to Caov-3 ovarian cancer cells in conjunction with paclitaxel
      induced apoptotic cell death through activation of caspase-9. Induction of
      apoptosis may mediate the anticancer effect of ABC294640 in ovarian cancer,
      although its precise antitumor mechanism is unclear. Ultimately, through its
      inhibition of S1P formation and subsequent effects on critical survival signaling
      cascades, ABC294640 may prove to be a useful adjunct to help re-sensitize tumors
      to standard therapy. 

PMID- 24023283
TI  - Comparing the effects of COX and non-COX-inhibiting NSAIDs on enhancement of
      apoptosis and inhibition of aberrant crypt foci formation in a rat colorectal
      cancer model.
AB  - The protection against colorectal cancer (CRC) by non-steroidal anti-inflammatory
      drugs (NSAIDs) is in part dependent on inhibition of cyclooxygenase (COX). We
      compared the efficacy of the non-COX-inhibiting R-flurbiprofen (R-FB) with COX
      inhibiting sulindac and racemic flurbiprofen (Rac-FB), and determined their
      effects on apoptosis, in an azoxymethane (AOM)-induced rat CRC model. In
      experiment 1, groups of rats were given a daily drug gavage (R-FB 30 mg/kg, Rac
      FB 10 mg/kg and Sulindac 20 mg/kg) for one week, followed by AOM treatment and
      were sacrificed eight hours later, colons were examined for apoptosis and cell
      proliferation. In experiment 2, groups of rats were given two AOM treatments,
      followed by a daily drug gavage until they were sacrificed ten weeks later, and
      colons were examined for aberrant crypt foci (ACF) and prostaglandin E2
      production. All drugs significantly enhanced apoptosis and inhibited ACF,
      irrespective of their COX-inhibiting potency (p<0.01), but sulindac was more
      potent in inhibition of large ACF, p<0.05. COX-inhibiting sulindac achieved the
      greatest protective effect. The greater safety profile of Rac-FB should provide
      an advantage for chemoprevention. 

PMID- 24023284
TI  - HOCl-dependent singlet oxygen and hydroxyl radical generation modulate and induce
      apoptosis of malignant cells.
AB  - The lack of extracellular superoxide anion production by non-transformed cells
      prevents H2O2/peroxidase-mediated HOCl synthesis by these cells, as well as
      apoptosis induction by exogenous HOCl. In contrast, transformed cells generate
      extracellular superoxide anions and HOCl, and die by apoptosis after
      HOCl/superoxide-dependent hydroxyl radical generation at their membrane. Tumor
      cells prevent HOCl synthesis through expression of membrane-associated catalase,
      but their extracellular superoxide anions readily react with exogenous HOCl. The
      interaction between HOCl and H2O2 causes singlet oxygen generation that
      inactivates superoxide dismutase (SOD) on the surface of the tumor cells and thus
      enhances HOCl-mediated apoptosis through an increase in free superoxide anions.
      Higher concentrations of singlet oxygen inactivate membrane-associated catalase
      and thus lead to partial inhibition of apoptosis induction by exogenous HOCl, due
      to consumption of HOCl by H2O2. The data presented here show a complex, but
      coherent picture of interactions between defined reactive oxygen species and
      protective enzymes on the surface of tumor cells. 

PMID- 24023285
TI  - Efficacy of liposomal curcumin in a human pancreatic tumor xenograft model:
      inhibition of tumor growth and angiogenesis.
AB  - BACKGROUND: Liposome-based drug delivery has been successful in the past decade,
      with some formulations being Food and Drug Administration (FDA)-approved and
      others in clinical trials around the world. The major disadvantage associated
      with curcumin, a potent anticancer agent, is its poor aqueous solubility and
      hence low systemic bioavailability. However, curcumin can be encapsulated into
      liposomes to improve systemic bioavailability. MATERIALS AND METHODS: We
      determined the antitumor effects of a liposomal curcumin formulation against
      human MiaPaCa pancreatic cancer cells both in vitro and in xenograft studies.
      Histological sections were isolated from murine xenografts and
      immunohistochemistry was performed. RESULTS: The in vitro (IC50) liposomal
      curcumin proliferation-inhibiting concentration was 17.5 MUM. In xenograft tumors
      in nude mice, liposomal curcumin at 20 mg/kg i.p. three-times a week for four
      weeks induced 42% suppression of tumor growth compared to untreated controls. A
      potent antiangiogenic effect characterized by a reduced number of blood vessels
      and reduced expression of vascular endothelial growth factor and annexin A2
      proteins, as determined by immunohistochemistry was observed in treated tumors.
      CONCLUSION: These data clearly establish the efficacy of liposomal curcumin in
      reducing human pancreatic cancer growth in the examined model. The therapeutic
      curcumin-based effects, with no limiting side-effects, suggest that liposomal
      curcumin may be beneficial in patients with pancreatic cancer.

PMID- 24023286
TI  - Stable knockdown of hCGbeta mRNA expression in bladder cancer cells results in
      significant growth inhibition.
AB  - BACKGROUND: Expression of human chorionic gonadotropin beta subunit (hCGbeta) by
      epithelial carcinomas is associated with a poor prognosis and has a proposed
      autocrine growth effect on cancer cells by inhibition of apoptosis. MATERIAL AND
      METHODS: We transduced the hCGbeta-expressing bladder cancer cell line SCaBER
      with short hairpin (sh) RNA lentiviral gene-specific (CGB) constructs and
      determined its impact on the synthesis of hCGbeta and the resultant effect on
      cancer cell growth. RESULTS: Stable CGB gene-silenced clones exhibited a 60%-80%
      reduction in the level of hCGbeta expressed and a reduced growth rate of more
      than 40% compared to wild-type SCaBER cells. CONCLUSIONS: shRNA Lentiviral
      particles achieve stable knockdown of hCGbeta translation in the bladder cancer
      cell line SCaBER. This transforms the phenotype by reducing hCGbeta expression
      and cell growth rate. This is consistent with the proposed autocrine/paracrine
      function of ectopic hCGbeta expression during oncogenesis.

PMID- 24023287
TI  - Antitumor activity of elacytarabine combined with bevacizumab, cetuximab and
      trastuzumab in human NSCLC xenografts.
AB  - AIM: The objective of the present study was to determine the in vivo antitumor
      activity of elacytarabine, the 5'-elaidic acid ester of arabinofuranosyl
      cytidine, alone and in combination with bevacizumab, cetuximab and trastuzumab in
      Vascular endothelial growth factor (VEGF), Epidermal growth factor receptor
      (EGFR)- and Human epidermal growth factor receptor 2 (HER2)-expressing non-small
      cell lung cancer xenografts. MATERIALS AND METHODS: The antitumor activity of
      elacytarabine, was tested at the maximal tolerable dose (MTD; 50 mg/kg) and half
      MTD (25 mg/kg), alone and in combination with the antibodies bevacizumab (5
      mg/kg), cetuximab (20 mg/kg) and trastuzumab (4 mg/kg) in two human non-small
      cell lung cancer xenografts. RESULTS: Elacytarabine exhibited very high activity
      in the EKVX xenograft at both dose levels, but was inactive in MAKSAX. Neither of
      the two xenografts were sensitive to bevacizumab or trastuzumab, but the MAKSAX
      xenograft showed intermediate response to cetuximab. The high sensitivity of EKVX
      to elacytarabine precluded the assessment of a potential benefit of the
      combinations with the antibodies. In the elacytarabine-, bevacizumab- and
      trastuzumab-insensitive MAKSAX xenograft, the combination of either bevacizumab
      or trastuzumab with elacytarabine at the MTD or half MTD resulted in intermediate
      activity, suggesting a beneficial effect of the combinations, whereas for
      cetuximab, the effect was enhanced when combined with elacytarabine given at the
      MTD, but not half-MTD. CONCLUSION: The results suggest that elacytarabine could
      be active in some cases of non-small cell lung cancer, and that the combination
      of elacytarabine and tyrosine kinase inhibitors may exert important additive or
      possibly synergistic effects of potential clinical benefit.

PMID- 24023288
TI  - High lung-metastatic variant of human osteosarcoma cells, selected by passage of
      lung metastasis in nude mice, is associated with increased expression of
      alpha(v)beta(3) integrin.
AB  - Altered expression of alphavbeta3 integrin is associated with tumor progression
      and metastasis in several types of cancer, including metastatic osteosarcoma. In
      this study, we demonstrate that in vivo passaging of lung metastasis in nude mice
      can generate an aggressive variant of human osteosarcoma cells. Experimental
      metastases were established by injecting 143B human osteosarcoma cells,
      expressing green fluorescent protein (GFP) in the nucleus and red fluorescent
      protein (RFP) in the cytoplasm, in the tail vein of nude mice. Lung metastases
      were harvested under fluorescence microscopy from nude mice to establish cell
      lines which were then injected via the tail vein of additional nude mice. This
      procedure was repeated for four passages in order to isolate highly metastatic
      variant sublines. When the parental and metastatic variants were transplanted
      orthotopically into the tibia of nude mice, the 143B-LM4 variant had the highest
      metastatic rate, approximately 18-fold higher than the parent (p<0.01).
      alphavbeta3 integrin expression was increased approximately 5.6-fold in 143B-LM4
      compared to parental cells (p<0.05). Thus, serial passage of lung metastases
      created a highly metastatic variant of human osteosarcoma cells which had
      increased expression of alphavbeta3 integrin, suggesting that alphavbeta3
      integrin plays an essential role in osteosarcoma metastasis. With this highly
      metastatic variant overexpressing alphavbeta3 integrin, it will now be possible
      to further investigate the mechanism by which alphavbeta3 integrin facilitates
      metastasis. 

PMID- 24023289
TI  - Effect of liposomal curcumin on red blood cells in vitro.
AB  - BACKGROUND: The anti-inflammatory and antiproliferative agent curcumin has poor
      oral bioavailability and solubility in plasma. Liposomal formulations have
      therefore been developed, but the toxicity of these preparations is not yet
      established. We investigated the influence of free and liposomally formulated
      curcumin on human red blood cell (RBC) morphology in vitro. MATERIALS AND
      METHODS: EDTA-buffered whole blood from two healthy individuals was incubated
      with different concentrations (1, 10, 100 MUg/ml) of free or liposomal curcumin.
      RBC morphology and mean cellular volume (MCV) were examined at up to 4 hours of
      incubation. RESULTS: Dose-dependent echinocyte formation was observed after
      incubation with free, and liposomal curcumin, with a threshold concentration of
      10 MUg/ml and peak effect after 30 minutes. A concomitant increase in mean
      cellular volume was detectable. CONCLUSION: Curcumin and liposomal curcumin cause
      dose-dependent changes in the shape of RBCs. This effect may represent an early
      sign of dose-limiting toxicity following intravenous administration.

PMID- 24023290
TI  - Prediction of immune surveillance responsive metastatic prostate cancer in pelvic
      lymph node and emergence of surveillance unresponsive/resistant metastatic cells.
AB  - BACKGROUND: Immune cells (lymphocytes and macrophages) provide the
      microenvironment for immune surveillance of metastatic prostate cancer (PCa)
      cells in pelvic lymph nodes. We have hypothesized that degeneration and/or
      apoptosis of metastatic PCa cells in pelvic lymph nodes can distinguish between
      aggressive and non-aggressive metastatic disease in patients. Our objective was
      to define the relationship between metastatic cell lysis and the presence of
      immune cells. MATERIALS AND METHODS: We studied archival primary PCa (n=38) and
      cancer-positive regional pelvic nodes (n=32) from the same patients undergoing
      radical retropubic prostatectomy at the Minneapolis Veterans Affairs Medical
      Center. RESULTS: Using morphological and immunohistochemical features of immune
      and metastatic cancer cells, we have identified progression of metastasis in the
      nodal compartments. Nodal parenchyma contained small, intermediate and large
      metastatic nodules/tumors. Immune surveillance occurred primarily in small tumors
      and surveillance was either absent or greatly reduced in intermediate and large
      tumors in nodes. Metastatic nodules/cells were lysed or became apoptotic when
      under immune-surveillance, as indicated by pyknotic nuclei and cytoplasm, the
      latter still had remnants of prostate specific antigen (PSA) staining. Metastatic
      cells without surveillance did not exhibit morphological features of cell
      degeneration (lysis) or apoptosis. Metastatic cells under immune-surveillance had
      an inverse relationship with those without immune-surveillance. This relationship
      differed from node to node and patient to patient. CONCLUSION: We have shown that
      at least two populations of metastatic cells were present in the nodes; the first
      group of cells was under immune surveillance, as indicated by limited to wide
      spread cell lysis/apoptosis, and the second group did not exhibit morphological
      evidence of cell lysis indicating emergence of surveillance-unresponsive
      (resistant) metastatic cells. These criteria can be used to distinguish
      metastatic cancer that is expected to be responsive to immunotherapy from that
      which would show little or no benefit from such treatment. Enhancement of immune
      surveillance and other treatments can be used to treat surveillance-unresponsive
      (resistant) disease to improve survival of patients.

PMID- 24023291
TI  - Enhanced redox factor 1 (REF1)-modulated p53 stabilization and JNK1 dissociation
      in response to selenomethionine.
AB  - AIM: p53 is reportedly activated without any genotoxicity through redox
      modulation of redox factor 1 (REF1). REF1 is documented to modulate the redox
      status under selenomethionine (SeMet). In this study, we investigated the
      mechanism of p53 stabilization by SeMet. MATERIALS AND METHODS: We mainly used
      ubiquitination assay and immunoprecipitation to determine the potential role of
      REF1 and c-jun N-terminal kinase 1 (JNK) in modulation of p53 stabilization by
      SeMet. RESULTS: The amount of ubiquitinated p53 decreased significantly under
      SeMet treatment, suggesting that SeMet might inhibit the proteasome-dependent
      degradation of p53. In addition, we observed that JNK was considerably associated
      with p53 in REF1 siRNA-treated cells, implying a possible role for SeMet-induced
      REF1 activity in modulation of the interaction between JNK and p53 via changes in
      p53 redox status. CONCLUSION: Our results suggest that the alternate mechanism of
      p53 stabilization by SeMet might provide an important clue in elucidating the
      molecular mechanism of chemopreventative compounds against various oxidative
      stresses.

PMID- 24023292
TI  - The neutrophil elastase inhibitor sivelestat suppresses accelerated
      gastrointestinal tumor growth via peritonitis after cecal ligation and puncture.
AB  - BACKGROUND: We examined whether tumor growth is enhanced by cecal ligation and
      puncture (CLP) and suppressed by a neutrophil elastase inhibitor, sivelestat.
      MATERIALS AND METHODS: C57BL/6 mice were divided in CLP/sivelestat, CLP alone,
      and control (simple laparotomy) groups. Murine CT26 colon carcinoma cells were
      injected subcutaneously into the back of each mouse and tumor growth and serum
      cytokine levels were assessed. RESULTS: Mice subjected to CLP alone exhibited
      enhanced tumor growth compared to controls with subcutaneously injected CT26
      cells (0.64+/-0.24 g vs. 0.021+/-0.027 g, p<0.001), while treatment with
      CLP/sivelestat produced smaller tumors than CLP alone (0.28+/-0.23 g vs. 0.64+/
      0.24 g, p=0.006). Cytokine assays showed suppressed production of interleukin
      (IL)-6 and IL-10 in the CLP/sivelestat group, and increased IL-6 and IL-10 in the
      CLP-alone group. CONCLUSION: Intra-abdominal inflammation induced by CLP enhances
      the growth of subcutaneously implanted tumors, while perioperative administration
      of sivelestat suppresses tumor growth by affecting systemic inflammation.

PMID- 24023293
TI  - Malignant progressive tumor cell clone exhibits significant up-regulation of
      cofilin-2 and 27-kDa modified form of cofilin-1 compared to regressive clone.
AB  - QR-32 is a regressive murine fibrosarcoma cell clone which cannot grow when they
      are transplanted in mice; QRsP-11 is a progressive malignant tumor cell clone
      derived from QR-32 which shows strong tumorigenicity. A recent study showed there
      to be differentially expressed up-regulated and down-regulated proteins in these
      cells, which were identified by proteomic differential display analyses by using
      two-dimensional gel electrophoresis and mass spectrometry. Cofilins are small
      proteins of less than 20 kDa. Their function is the regulation of actin assembly.
      Cofilin-1 is a small ubiquitous protein, and regulates actin dynamics by means of
      binding to actin filaments. Cofilin-1 plays roles in cell migration,
      proliferation and phagocytosis. Cofilin-2 is also a small protein, but it is
      mainly expressed in skeletal and cardiac muscles. There are many reports showing
      the positive correlation between the level of cofilin-1 and cancer progression.
      We have also reported an increased expression of cofilin-1 in pancreatic cancer
      tissues compared to adjacent paired normal tissues. On the other hand, cofilin-2
      was significantly less expressed in pancreatic cancer tissues. Therefore, the
      present study investigated the comparison of the levels of cofilin-1 and cofilin
      2 in regressive QR-32 and progressive QRsP-11cells by western blotting. Cofilin-2
      was significantly up-regulated in QRsP-11 compared to QR-32 cells (p<0.001). On
      the other hand, the difference of the intensities of the bands of cofilin-1 (18
      kDa) in QR-32 and QRsP-11 was not significant. However, bands of 27 kDa showed a
      quite different intensity between QR-32 and QRsP-11, with much higher intensities
      in QRsP-11 compared to QR-32 (p<0.001). These results suggested that the 27-kDa
      protein recognized by the antibody against cofilin-1 is a possible biomarker for
      progressive tumor cells. 

PMID- 24023294
TI  - Effects of dietary calcium on Helicobacter pylori-induced gastritis in Mongolian
      gerbils.
AB  - BACKGROUND AND AIMS: Helicobacter pylori (Hp) infection causes gastritis and is
      considered a gastric cancer risk factor. We have previously reported that codfish
      meal markedly enhanced Hp-induced gastritis in Mongolian gerbils. In the present
      study, we sought the responsible components in codfish meal. MATERIALS AND
      METHODS: Codfish were divided into three parts (meat, viscera and 'other parts',
      including bone), and administered to Hp-infected gerbils. Subsequently, cod bone,
      sardine bone and prawn shell were tested, along with major calcium components,
      hydroxyapatite and calcium carbonate, in bone and shell, respectively. RESULTS:
      'Other parts' and cod bone enhanced Hp-induced gastritis, as was observed for
      whole codfish. Similarly, sardine bone and prawn shell, as well as 0.22-0.88%
      hydroxyapatite and calcium carbonate, enhanced gastritis. In contrast,
      administration of a higher dose of the calcium compounds exerted protective
      effects. CONCLUSION: Intake of calcium compounds may contribute to enhancement of
      Hp-induced gastritis.

PMID- 24023295
TI  - Vagus nerve regulates breast cancer metastasis to the adrenal gland.
AB  - BACKGROUND: Metastasis of breast cancer to adrenal glands may alter
      neuroendocrine functions which increase the severity of the disease. In this
      study the role of vagus nerve activity in adrenal metastases was examined.
      MATERIALS AND METHODS: 48 Balb/c mice (n=48) were divided into four groups;
      control, sham-operated, right vagotomy or left vagotomy. Vagotomies were
      performed one week before orthotopic injection of 4THM breast carcinoma cells and
      the degree of adrenal metastasis was assessed. RESULTS: In control animals,
      besides extensive metastases within and around the adrenal, 70% loss of medulla
      was observed which was significantly more than cortical loss. Sham operation by
      itself significantly decreased both the extent of metastases and medullary loss.
      Compared to sham group, vagotomy increased intra- and extra-adrenal metastasis.
      There was laterality in the regulation of metastasis by the vagus nerve, such
      that the right adrenal gland was affected the most. CONCLUSION: Vagus nerve
      activity may reduce adrenal metastasis as well as tumor-induced alterations of
      adrenal functions.

PMID- 24023296
TI  - Association of slow acetylation profile of NAT2 with breast and gastric cancer
      risk in Brazil.
AB  - BACKGROUND: The N-acetyltransferase 2 (NAT2) gene is a marker for the study of
      interindividual susceptibility to developing neoplasias. The purpose of this
      study was to verify a possible association between single nucleotide
      polymomorphisms (SNPs) of NAT2 and the susceptibility to gastric cancer (GC) and
      breast cancer (BC) in patients from the North region of Brazil. MATERIALS AND
      METHODS: Five SNPs of the NAT2 gene were investigated by direct sequencing.
      Ancestry was estimated by analysis of a panel with 48 ancestry-informative
      markers (AIM). RESULTS: Individuals with slow acetylation profile had an
      increased risk of developing neoplasias up to three times when compared to
      controls. CONCLUSION: In this study, slow acetylation profile was found to
      strongly influence susceptibility to GC and BC.

PMID- 24023297
TI  - Fluoxetine-induced apoptosis in hepatocellular carcinoma cells.
AB  - BACKGROUND: In addition to being used to treat mental disorders, a serious
      complication of cancer, antidepressants have been reported to improve cancer
      patient immunity, inhibit cell growth and have an antitumor effect on various
      cancer cell lines. We investigated the apoptotic effect of fluoxetine against the
      Hep3B human hepatocellular carcinoma cell line. MATERIALS AND METHODS: After
      treatments of Hep3B cells with fluoxetine, we measured cell viability, reactive
      oxygen species (ROS), mitochondrial membrane potential (MMP) and activation of
      mitogen-activated protein kinases (MAPK). RESULTS: Fluoxetine reduced the
      viability of cancer cells, induced loss of MMP and formation of ROS, reduced
      expression of extracellular signal-regulated kinase 1/2 and increased expression
      of c-JUN N-terminal kinase and p38 MAPK. N-Acetylcysteine, an oxidant-scavenger,
      and 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM), an
      intracellular Ca(2+) chelator, prevented fluoxetine-induced modulation of MAPK.
      CONCLUSION: Fluoxetine appears to exhibit an apoptotic effect against Hep3B cells
      through the loss of MMP, formation of ROS and modulation of MAPK activities.

PMID- 24023298
TI  - Tropomyosin-related kinase B inhibitor has potential for tumor regression and
      relapse prevention in pulmonary large cell neuroendocrine carcinoma.
AB  - Large cell neuroendocrine carcinoma (LCNEC) has an especially poor prognosis, and
      an effective therapeutic strategy has yet to be established. We have previously
      shown that the expressions of tropomyosin-related kinase B (TRKB) and brain
      derived neurotrophic factor (BDNF) are high in LCNEC and that TRKB/BDNF signaling
      is involved in the proliferation, tumorigenesis, and invasive nature of LCNEC.
      Therefore, TRKB/BDNF signaling may offer a potential therapeutic target for LCNEC
      treatment. In the present study, we evaluated whether the TRKB tyrosine kinase
      inhibitor, k252a, has effects on tumor regression and relapse prevention on
      LCNEC, using a murine xenograft model. The LCNEC cell line and NCI-H810 cells
      were subcutaneously implanted into the flanks or intrathoracically injected into
      the bilateral pleural cavities of BALB/c nude mice. k252a significantly inhibited
      tumor volume, expression of matrix metalloproteinases and the formation of
      pleural dissemination by LCNEC. These results suggest that k252a has potential
      for tumor regression and relapse prevention in LCNEC. Since many patients with
      LCNEC suffer through the use of ineffective therapeutic strategies, a clinical
      trial using the TRKB inhibitor for LCNEC is urgently required. 

PMID- 24023299
TI  - HER2/neu gene determination in women screened for breast carcinoma: how screening
      programs reduce the skyrocketing cost of targeted therapy.
AB  - Few data on Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast
      carcinomas have been reported for screen-detected breast carcinoma. Assessing the
      impact of a targeted intervention with anti-HER2 inhibitors on costs is required
      in order to plan for better strategies in screening programs. A total of 54,472
      women were screened and 323 cases were found to be invasive cancer. We performed
      immunophenotypical-fluorescent in situ hybridization (FISH) analysis. Among 153
      evaluable breast carcinomas, tumours displayed a 3+ scoring status 3+ in 16
      (10%), 2+ in 12 (8%), 1+ in 29 (19%) and 0 in 96 (63%) of cases, respectively.
      All 3+ HER2+ cases and 2/12 2+ (17%) cases exhibited HER2/neu gene amplification,
      the remaining cases did not. In contrast to the higher incidence reported at the
      population level, 20-30% HER2-positive cases for metastatic carcinomas, and only
      11% of the screen-detected breast carcinomas displayed HER2/neu gene
      amplification. Breast cancer detection by screening programs hijacks the
      skyrocketing cost of the use of targeted therapy in HER2-positive carcinoma. 

PMID- 24023300
TI  - Differential expression of p-mTOR in cutaneous basal and squamous cell carcinomas
      likely explains their different response to mTOR inhibitors in organ-transplant
      recipients.
AB  - BACKGROUND: Mammalian Target of Rapamycin (mTOR) inhibitors, such as sirolimus
      and everolimus, have been shown to reduce cutaneous carcinogenesis in organ
      transplant recipients requiring for immunosuppressive treatment to prevent from
      allograft rejection. Clinical observations suggest that cutaneous squamous cell
      carcinomas (SCC) are more sensitive than basal cell carcinomas (BCC) to the
      antitumoral effect of these inhibitors. AIM: To investigate if the different
      response of SCC and BCC to mTOR inhibitors can be explained by differential
      expression of molecules involved in the mTOR signaling pathway. MATERIALS AND
      METHODS: The expression of phospho-mTOR was immunohistocemically studied in
      specimens of cutaneous SCC and BCC. Results. All 15 SCCs expressed significant
      cytoplasmic phospho-mTOR immunoreactivity; by contrast, 12/13 BCC were completely
      negative, only one BCC exhibited weak phospho-mTOR immunoreactivity. CONCLUSION:
      The considerably higher expression of phospho-mTOR in SCC compared to BCC is a
      likely explanation for their higher sensitivity to mTOR inhibitors.

PMID- 24023301
TI  - Tumor-stromal interactions with direct cell contacts enhance motility of non
      small cell lung cancer cells through the hedgehog signaling pathway.
AB  - The metastatic potential of non-small cell lung cancer (NSCLC) has been shown to
      be associated with interactions with the tumor microenvironment, which primarily
      comprises of cancer-associated fibroblasts (CAFs). Heterotypic cell-cell
      interactions occur via released signaling molecules and direct physical contact.
      To investigate the differential contribution of direct cell-cell contact and
      paracrine signaling factors to NSCLC metastasis, we performed two types of co
      cultures: direct co-cultures of the NSCLC cell line H358 with primary cultures of
      CAFs from patients with resected NSCLC; and indirect co-cultures across a
      separable membrane. We showed that CAFs more potently induce epithelial-to
      mesenchymal transition (EMT) in NSCLC H358 cells through direct contacts than
      through indirect interactions, as indicated by an elongated and disseminated
      appearance. Immunocytochemical experiments show that EMT accompanies the
      expression of mesenchymal cytoskeletal proteins, including vimentin. However,
      H358 cells proliferate more slowly in direct co-culture than in indirect co
      culture. Real-time reverse transcription-polymerase chain reaction (RT-PCR)
      revealed that H358 cells in direct contact with CAFs up-regulate the expression
      of the pan-mesenchymal markers alpha-smooth muscle actin (alpha-SMA), fibroblast
      activation protein (FAP), transforming growth factor-beta (TGFbeta) signaling
      effector SMAD family number-3 (SMAD3), and hedgehog signaling effector GLI family
      zinc finger-1 (GLI1), compared with the indirect co-culture system. Furthermore,
      we found that the direct GLI1 transcription targets snail family zinc finger-1
      (SNAI1) and SNAI2 are up-regulated, suggesting that the hedgehog signaling
      pathway is active in direct co-culture. A scratch wound assay showed that direct
      contact co-culture increases the motility of H358 cells. In conclusion, these
      findings provide evidence that paracrine factors and direct physical contact
      between NSCLC cells and CAFs might control the metastatic potential of NSCLC
      through the hedgehog signaling pathway. 

PMID- 24023302
TI  - The diagnostic value of alcohol dehydrogenase isoenzymes and aldehyde
      dehydrogenase measurement in the sera of patients with endometrial cancer.
AB  - BACKGROUND/AIM: The aim of this study was to investigate the potential role of
      alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) as tumor markers
      for endometrial cancer. PATIENTS AND METHODS: Serum samples were obtained from 40
      women with endometrial cancer, 52 with myoma uteri and 52 healthy individuals.
      Class III, IV of ADH and total ADH activity was measured by a photometric method
      and class I, II ADH and ALDH activity, by a fluorometric method. RESULTS: The
      total activity of ADH and ADH class I was significantly higher in the serum of
      patients with endometrial cancer than in healthy individuals and patients with
      myoma. The diagnostic sensitivity for ADH I was 69%, specificity 77%, positive
      predictive value and negative predictive value were 75% and 71% respectively. The
      area under curve for ADH I was 0.682 and for total ADH was 0.623. CONCLUSION: The
      results suggest a potential role of ADH I as a marker for endometrial cancer.

PMID- 24023303
TI  - Utility of ATP7B in prediction of response to platinum-based chemotherapy in
      urothelial bladder cancer.
AB  - BACKGROUND: Platinum-based chemotherapy is the treatment of choice for metastatic
      urothelial carcinoma, which is limited by primary and secondary resistance of the
      tumour. The Cu(2+) transporting beta polypeptide ATPase (ATP7B) is believed to
      play a role in this resistance. The aim of this study was to screen the ATP7B
      gene for mutations and loss of heterozygosity in bladder cancer and to evaluate
      their impact on chemotherapy resistance. MATERIALS AND METHODS: DNA extracted
      from 17 patients with metastatic bladder cancer was analyzed by DNA sequencing,
      and microsatellite analysis. RESULTS: We found 12 non-synonymous mutations and 20
      synonymous mutations out of which 11 and 15, respectively, have not been
      previously described. Results were correlated with response to platinum-based
      chemotherapy: 65% of patients exhibited LOH of the ATP7B locus on chromosome
      13q14.3, with a tendency to have a better response to chemotherapy. CONCLUSION:
      Although resistance is complex, LOH at the ATP7B locus might be useful in
      predicting chemotherapy response and needs further evaluation.

PMID- 24023304
TI  - Antitumorigenic effect of dietary natural compounds via lipid metabolism
      modulation in Apc(Min/+) mice.
AB  - AIM: The aim of the present study was to evaluate the effects of a diet
      supplementation with either olive oil, or n-3 or n-6-polyunsaturatedFatty acids
      (PUFAs) on tumour development and gene expression for lipogenic enzymes in
      Apc(Min/+) mice. MATERIALS AND METHODS: In the control group, the mice received a
      standard diet, the OO group was fed on a diet with 12% olive oil, the OM-3 group
      with 12% salmon fish rich in n-3 PUFAs, the OM-6 group with 12% oenothera oil
      rich in n-6 PUFAs. Gene expression of lipogenic enzymes was evaluated by real
      time reverse transcription polymerase chain reaction. RESULTS: All mice in the
      treated groups presented a reduction in total intestinal polyp number and load,
      which was particularly marked in the OM-3 group. Treated mice showed an induction
      of low density lipoprotein receptor gene expression and a significant reduction
      of expression of lipogenic gene. CONCLUSION: Our data provide new insights into
      the mechanism of cell growth inhibition and apoptotic regulation by dietary olive
      oil and PUFAs in Apc(Min/+) mice.

PMID- 24023305
TI  - Expression of alphaB-crystallin and vascular endothelial growth factor in
      conjunctival squamous cell carcinoma.
AB  - AIM: To examine the expression of alphaB-crystallin and vascular endothelial
      growth factor (VEGF) in conjunctival squamous cell carcinoma (CSCC). MATERIALS
      AND METHODS: Seven CSCCs and three normal conjunctivas that were surgically
      excised were studied. Paraformaldehyde-fixed, paraffin-embedded tissue sections
      were processed for immunohistochemistry with antibodies against alphaB
      crystallin, its phosphorylated forms, and VEGF. In vitro experiments were
      conducted to investigate the effects of mitomycin C (MMC) treatment on the
      expression of alphaB-crystallin and VEGF secretion. RESULTS: alphaB-Crystallin
      and VEGF were strongly expressed in CSCCs compared to normal conjunctivas. alphaB
      Crystallin immunoreactivity was co-localized with that for VEGF in CSCCs, whereas
      these signals were reduced in CSCC tissues treated with MMC before excision. MMC
      treatment suppressed the alphaB-crystallin expression and VEGF secretion in
      cultured conjunctival cells in a dose-dependent manner. CONCLUSION: This study
      demonstrated alphaB-crystallin and VEGF expressions in human CSCCs, which may
      play a role in the pathogenesis. alphaB-Crystallin expression, and VEGF secretion
      were reduced by MMC, indicating a novel therapeutic mechanism in MMC treatment
      for human CSCC.

PMID- 24023306
TI  - Combination of the EGFR tyrosine kinase inhibitor AG1478 and 5-FU: no synergistic
      effect on EGFR phosphorylation, cell proliferation and apoptosis induction.
AB  - The combination of a fluoropyrimidine with receptor tyrosine kinase inhibitors in
      tumor treatment has been proposed to enhance their therapeutic efficiency. The
      synergism of such a combination in the treatment of colorectal carcinoma is
      equivocal although the epidermal growth factor receptor (EGFR) is frequently
      overexpressed in the tumors. We used human colorectal SW 480 cells, to analyze
      the EGFR phosphorylation levels. We showed that incubation of cells with 5
      fluorouracil (5-FU) does not influence EGFR phosphorylation of tyrosine 1173 and
      the overall phosphorylation after stimulation. Inhibition of EGFR phosphorylation
      with AG1478 reduced cell proliferation compared to 5-FU. Cells exhibited highest
      apoptosis rates with 5-FU. AG1479 inhibited cell proliferation more potently than
      5-FU alone. Apoptosis rates after incubation with AG1478 alone and AG1478 in
      combination with 5-FU were significantly lower than apoptosis induction by 5-FU
      alone. Therefore, no synergism of both substances can be demonstrated. This
      experimental data argues against the combination of EGFR-inhibitors with 5-FU in
      a clinical setting. 

PMID- 24023307
TI  - PTK7 expression in triple-negative breast cancer.
AB  - BACKGROUND: Protein tyrosine kinase-7 (PTK7) plays an important role in cancer.
      Our aim was to evaluate PTK7 in triple-negative breast cancer (TNBC). MATERIALS
      AND METHODS: PTK7 Expression was assessed by immunohistochemistry (IHC) in 133
      patients with TNBC. Expression levels were correlated with clinicopathological
      features and survival, taking chemotherapy into account. RESULTS: Positive PTK7
      expression was detected in 28.6% of tumors. In the total population, no
      significant difference was detected in disease-free survival (DFS) or overall
      survival (OS) related to PTK7 status. However, in patients treated by
      chemotherapy, patients with PTK7-negative tumors seemed to have better DFS than
      those with PTK7-positive tumors, particularly for patients treated with only
      anthracycline-therapy drugs. In patients receiving other chemotherapy regimens,
      PTK7 status had no significant impact on DFS or OS. CONCLUSION: Our results
      support earlier findings that PTK7 may be associated with resistance to
      anthracycline-based chemotherapy.

PMID- 24023308
TI  - Frequent promoter methylation of CDH1 in non-neoplastic mucosa of sporadic
      diffuse gastric cancer.
AB  - BACKGROUND/AIM: To identify promoter methylation as a major silencing mechanism
      in potential precursor lesions of sporadic diffuse gastric cancer (DGC), we
      investigated promoter methylation of CDH1 (E-Cadherin gene) in a series of DGCs
      and matched normal mucosa. MATERIALS AND METHODS: The extent of CDH1 gene
      promoter methylation was explored using methylation-specific polymerase chain
      reaction (MSP) and pyrosequencing (PS) in 72 DGCs with a matched pair of normal
      mucosa. RESULTS: MSP and PS revealed CDH1 promoter methylation in 73.6% (53/72)
      and 77.8% (56/72) of DGC samples, respectively. PS detected CDH1 methylation in
      70.8% (51/72) and 72.2% (52/72) of matched normal mucosa from adjacent and remote
      foci, respectively. In comparison, CDH1 promoter methylation was detected in
      12/24 normal gastric mucosa samples without DGC, and this difference was
      statistically significant (p=0.016). CONCLUSION: The current study showed that
      the majority of DGC cases demonstrated concurrent CDH1 promoter methylation in
      tumor tissues and in non-neoplastic mucosa.

PMID- 24023309
TI  - ESR1 gene amplification in endometrial carcinomas: a clinicopathological
      analysis.
AB  - This study investigated the clinicopathological significance of estrogen receptor
      1 (ESR1) gene amplification and its relationship to phosphatase and tensin
      homolog (PTEN), human epidermal growth factor receptor 2 (HER2), MutL homolog 1
      (MLH1), p53, and AT rich interactive domain 1A (ARID1A) expression in endometrial
      carcinomas. ESR1 amplification and expression were assessed by fluorescence in
      situ hybridization and immunohistochemistry. Clinical data were collected by
      retrospective chart review. ESR1 amplification was identified in 13 out of 111
      (11.7%) endometrial carcinomas. No significant association was observed between
      ESR1 amplification and International Federation of Gynecology and Obstetrics
      (FIGO) stage (p=0.17), histological grade (p=0.35), lymph node metastasis
      (p=0.51), or deep myometrial invasion (p=0.46). ESR1 amplification was
      independent of PTEN, p53, HER2, MLH1, and ARID1A protein expression. Patients
      without estrogen receptor (ER) or progesterone receptor (PR) expression had
      shorter progression-free and overall survival than those with ER or PR expression
      (p<0.01). ESR1 amplification is independent of known clinicopathological factors
      related to poor prognosis and PTEN, p53, HER2, MLH1, and ARID1A protein
      expression, suggesting ESR1 amplification may be an early event in endometrial
      carcinoma development. 

PMID- 24023311
TI  - Lewis lung carcinoma progression is facilitated by TIG-3 fibroblast cells.
AB  - BACKGROUND: The interactions of tumor cells with stromal fibroblasts influence
      tumor biology, but the exact mechanisms involved are still unclear. In the
      present study, we evaluated the effects of a human lung fibroblast cell line, TIG
      3, on Lewis lung carcinoma (LLC) cells both in vitro and in vivo. MATERIALS AND
      METHODS: LLC and TIG-3 cells were co-cultured/co-implanted in vitro and in vivo.
      Cell invasion was assayed. Local tumor growth, as well as lung metastasis, were
      evaluated after subcutaneous cell co-implantation into NOD/SCID/gamma-null (NOG)
      mice. LLC, and TIG-3 cells were pre-treated with either SB431542, a small
      molecule TGF-beta receptor antagonist, or siRNA for transforming growth factor
      (TGF)-beta before co-culture or co-implantation, and the effects of pre
      treatments were compared both in cell culture and in mice. RESULTS: Subcutaneous
      LLC tumor growth (L group) in NOG mice was significantly increased by co
      implantation of TIG-3 cells (L+T group) at four weeks. The number of macroscopic
      lung metastases was also significantly increased in the L+T group in comparison
      to the L group. In vitro cell invasion was significantly increased in the L+T
      group in comparison to the L group. In vitro expression of phosphorylated-SMAD3
      was significantly increased in the L+T group in comparison to the L group.
      Furthermore, pre-treatment with either SB431542 or siRNA for TGF-beta reduced the
      invasiveness both in culture and in mice. CONCLUSION: This study suggested that
      in vitro as well as in vivo progression of LLC was facilitated by co-culture/co
      implantation with TIG-3 cells, and that this process was at least in part
      dependent on TGF-beta-mediated interactions.

PMID- 24023310
TI  - Macrophage apolipoprotein E and proliferation of MCF-7 breast cancer cells: role
      of LXR.
AB  - BACKGROUND: Apolipoprotein E (APOE), a lipid transport protein that has a key
      role in the lipoprotein metabolism, is expressed by macrophages under the control
      of the transcription factor Liver X Receptor (LXR), an oxysterol-activated
      transcriptional factor involved in cholesterol metabolism. Recent work has shown
      that LXR agonists may inhibit breast cancer cell proliferation in vitro. We
      hypothesized that LXR-activated macrophages, and in particular secreted
      macrophagic APOE, may potentiate the effect of LXR agonists. Our goal was to
      evaluate the effect of APOE, secreted by THP-1 macrophages under the control of
      LXR, on MCF-7 cell proliferation, a model of breast cancer. MATERIALS AND
      METHODS: MCF-7 cells were incubated with supernatants from THP-1 cells previously
      treated with LXR agonists [T0901317 or 22(R)-hydroxycholestrol], or supernatants
      from THP-1 cells transfected with siRNA against APOE mRNA. RESULTS: Viability
      assays and cell death quantification showed that media from LXR-activated
      macrophages reduced cell proliferation and increased apoptosis of MCF-7 cells.
      Interestingly, the opposite effects were observed when MCF-7 cells wre treated
      with media from the siRNA APOE-mediated knock-down model. CONCLUSION: This study
      highlights the protective role of LXR-activated macrophages against breast cancer
      growth, and the implication of APOE protein in the anti-proliferative and pro
      apoptotic effects observed.

PMID- 24023312
TI  - Multiple anticancer effects of damsin and coronopilin isolated from Ambrosia
      arborescens on cell cultures.
AB  - Terpenoids in plants are important sources for drug discovery. In this study, we
      extracted damsin and coronopilin, two sesquiterpene lactones, from Ambrosia
      arborescens and examined their anticancer effects on cell cultures. Damsin and
      coronopilin inhibited cell proliferation, DNA biosynthesis and formation of
      cytoplasmic DNA histone complexes in Caco-2 cells, with damsin being more potent
      than coronopilin. Further studies using the luciferase reporter system showed
      that damsin and coronopilin also inhibited expressions of nuclear factor-kappaB
      (NF-kappaB) and signal transducer and activator of transcription-3 (STAT3),
      indicating that these sesquiterpenes can interfere with NF-kappaB and STAT3
      pathways. Finally, we examined the effects of two synthetic dibrominated
      derivatives of damsin, 11alpha,13-dibromodamsin and 11beta,13-dibromodamsin.
      While bromination appeared to weaken the antiproliferative effects of damsin, the
      beta epimer had strong inhibitory effects on STAT3 activation. In conclusion, the
      sesquiterpene lactones damsin and coronopilin have inhibitory effects on cell
      proliferation, DNA biosynthesis and NF-kappaB and STAT3 pathways, thus being
      potentially important for discovery of drugs against cancer. 

PMID- 24023313
TI  - Zoledronic acid-induced cytotoxicity through endoplasmic reticulum stress
      triggered REDD1-mTOR pathway in breast cancer cells.
AB  - BACKGROUND: Zoledronic acid (ZOL) used for the prevention/treatment of
      osteopathic complications has been reported to have antitumor effects in breast
      cancer treatment. However, little is known about the exact molecular mechanisms
      for antitumor actions of ZOL. In this study, two breast cancer cell lines were
      used to investigate the antitumor efficacy of ZOL and the underlying molecular
      mechanisms. RESULTS: The growth of two breast cancer cell lines was markedly
      decreased following treatment with ZOL. Compared with MCF-7 cells, MDA-MB-231
      cells were more sensitive to ZOL treatment. Western blot analysis showed that the
      inhibitory effect of zoledronic acid on growth was related to the extent of
      inhibition of phosphorylated-protein kinase B (p-AKT), and phosphorylated
      mammalian target of rapamycin (p-mTOR). Moreover, the expression of the stress
      responsive protein regulated in development and DNA damage response 1 (REDD1), an
      inhibitor of mTOR, was induced markedly to various degrees in different breast
      cancer cell lines after ZOL treatment. Interestingly, by examining the upstream
      signaling pathway of REDD1, we found that ZOL can induce endoplasmic reticulum
      stress responses through activating the protein kinase R (PKR)-related ER kinase
      eukaryotic initiation factor 2 alpha-CCAAT/enhancer binding protein homologous
      protein (PERK-eIF2alpha-CHOP) pathway. CONCLUSION: Taken together, these results
      indicated that ZOL-induced cell death was caused by endoplasmic reticulum stress
      activating PERK-eIF2alpha-CHOP pathway to induce REDD1 expression and inhibit the
      mTOR pathway.

PMID- 24023314
TI  - Vascular endothelial growth inhibitor (VEGI) is an independent indicator for
      invasion in human pituitary adenomas.
AB  - Pituitary ademonas are benign tumours from the pituitary gland but may have an
      invasive and destructive growth pattern. There is little understanding of the
      growth and progression control of pituitary tumours. In the present study, we
      investigated the expression of vascular endothelial growth inhibitor (VEGI), a
      vascular endothelial growth and apoptosis regulator and VEGI receptor Death
      Receptor-3 (DR3), in clinical pituitary tumours. Pituitary tumours from 95
      patients were included in the study. Fresh pituitary tumours were obtained
      immediately after surgery and processed for histological and molecular-based
      analyses. Histopathological and clinical information including tumour size,
      tumour invasion and endocrine status were analyzed against the gene transcript
      expression of VEGI, DR3 and VEGF. VEGI and VEGF family and VEGF receptors were
      quantitatively determined for their gene transcript expression. The expression
      levels of VEGI were significantly lower in pituitary tumours which invaded the
      sella floor, and with suprasellar extension than in non-invasive tumours
      (p=0.0073). VEGI levels were also negatively correlated with cavernous sinus
      invasion stage (p<0.0001), in that a high level of VEGI was associated with low
      tumour grade. Multivariate analysis indicated that VEGI is an independent factor
      predictive of invasion (p=0.05). It was further demonstrated that the
      relationship between VEGI and pituitary tumour invasion were independent of the
      expression of VEGF and its receptors. Low levels of VEGI transcripts were
      associated with the intratumoural haemorrhage (p=0.05). Out of all the pituitary
      tumours, 59 were non-functional. Out of the functional tumours, it was found that
      follicle stimulating hormone (FSH)-expressing and gonadotrophic tumours tended to
      have markedly low levels of VEGI transcripts, compared with non-functional
      tumours (p=0.0026 and p=0.003, respectively). The opposite was seen with thyroid
      stimulating hormone (TSH)-secreting tumours. Levels of DR3 in tumours with sella
      destruction were also lower than in those without destruction. VEGI, possibly via
      DR3, suppresses the aggressive nature of pituitary tumours and its expression
      level is closely linked to the invasion and destruction of the suprasellar and
      sella regions. It also has implications for the endocrine nature of these
      tumours. VEGI thus has an important predictive and prognostic value in patients
      with pituitary tumours. 

PMID- 24023315
TI  - Combination metronomic oral topotecan and pazopanib: a pharmacokinetic study in
      patients with gynecological cancer.
AB  - BACKGROUND: Combination metronomic topotecan plus pazopanib is active against
      preclinical models of gynecological cancer. Both agents are substrates for ATP
      binding cassette family transporters so there is an increased likelihood for
      pharmacokinetic (PK) drug-drug interactions. PATIENTS AND METHODS: PK analyses of
      topotecan were performed during three cycles of a phase I dose-escalation study
      of metronomic topotecan and pazopanib in consenting adult patients with
      gynecological cancer. Concentration time data were analyzed using a population PK
      approach. RESULTS: Twenty-one patients were evaluable for serial PK studies.
      Considerable inter- and intra-patient variability was observed in the PK
      parameters, attributable primarily to highly variable oral bioavailability. No
      difference in topotecan disposition was detected between administration cycles,
      nor between the off- versus on-pazopanib studies. CONCLUSION: The lack of a
      statistically significant drug-drug interaction agrees with preclinical findings
      suggesting that pazopanib does not influence the PK of metronomic topotecan. No
      adjustment of low dose metronomic topotecan dosing is merited when used in
      conjunction with pazopanib.

PMID- 24023316
TI  - Docetaxel in the treatment of non-small cell lung cancer (NSCLC) -- an
      observational study focusing on symptom improvement.
AB  - BACKGROUND: Results of an observational study on docetaxel-based therapy in non
      small cell lung cancer (NSCLC) with focus on symptom control and therapy
      response, are reported. PATIENTS AND METHODS: A total of 233 patients with NSCLC
      treated with docetaxel-containing therapy were analyzed. RESULTS: The pre
      existing symptoms of cough, dyspnea and pain markedly improved after three cycles
      of docetaxel-based therapy. Regression of symptoms was strongly associated with
      therapy response, but unexpectedly, patients with stable disease had also a
      substantial benefit. Alltogether, the response after three cycles was complete in
      0.9% and partial in 26.6% of patients, respectively. CONCLUSION: Symptom control
      was achieved in the majority of cases, which received three cycles of docetaxel
      based therapy. Thus, a clinical benefit was regularly reached shortly after
      initiation of chemotherapy.

PMID- 24023317
TI  - Efficacy of combined androgen blockade with zoledronic acid treatment in prostate
      cancer with bone metastasis: the ZABTON-PC (zoledronic acid/androgen blockade
      trial on prostate cancer) study.
AB  - AIM: Zoledronic acid (ZA) reduces the risk of skeletal-related events (SREs) in
      castration-resistant prostate cancer (CRPC) with bone metastasis and improves
      quality of life. It remains unclear when clinicians should initiate ZA treatment.
      PATIENTS AND METHODS: Hormone-naive patients were randomized to a combined
      androgen blockade (CAB) group or CAB with ZA group (CAB-ZA) based on Gleason
      score (GS) or extent of disease. The primary end-point of the study was
      progression-free survival (PFS) and the secondary end-point was incidence of SREs
      and bone pain. RESULTS: Thirty-one and 29 patients among 60 enrolled patients
      were assigned to the CAB group and the CAB-ZA group, respectively. There was no
      significant difference in PFS between the two groups. Subgroup analyses revealed
      better PFS in the CAB-ZA group with GS >=8 (p=0.021). Moreover, incidence of
      SREs, including bone pain, was lower in the CAB-ZA group (p=0.019). CONCLUSION:
      CAB-ZA treatment was found to improve PFS for patients with prostate cancer with
      high GS. CAB-ZA treatment could be recommended for treatment of patients with
      prostate cancer.

PMID- 24023318
TI  - Pharmacokinetic assessment of irinotecan, SN-38, and SN-38-glucuronide: a
      substudy of the FIRIS study.
AB  - BACKGROUND: We evaluated the pharmacokinetics of irinotecan (CPT-11) and its
      metabolites in patients with metastatic colorectal cancer receiving the
      combination of CPT-11/S-1 (IRIS) or 5-fluorouracil (5-FU)/l-leucovorin (LV)/CPT
      11 (FOLFIRI) regimens in the FIRIS trial. PATIENTS AND METHODS: Serum CPT-11, SN
      38 (an active metabolite of CPT-11), and SN-38-glucuronide concentrations were
      compared between the IRIS and FOLFIRI regimens, and between days 1 and 15 of
      administration. Correlations between pharmacokinetic data and incidence of
      neutropenia and diarrhea were also assessed. RESULTS: There were no significant
      differences in the pharmacokinetics of CPT-11 or its metabolites between days 1
      and 15. SN-38 concentrations were correlated with the occurrence of neutropenia,
      which was significantly more frequent in the FOLFIRI group than in the IRIS
      group. CONCLUSION: No alterations in CPT-11 pharmacokinetics after repeated IRIS
      or FOLFIRI administration were observed. Neutropenia was more frequent in the
      FOLFIRI group than in the IRIS group because exposure to SN-38 was greater in the
      former group.

PMID- 24023319
TI  - Immunological response after WT1 mRNA-loaded dendritic cell immunotherapy in
      ovarian carcinoma and carcinosarcoma.
AB  - BACKGROUND: Dendritic cell (DC)-based immunotherapy is an emerging new treatment
      option in ovarian cancer, an important cause of cancer-related mortality.
      PATIENTS AND METHODS: One patient with ovarian carcinosarcoma (OCS) and one with
      serous ovarian cancer (SOC) received four weekly vaccinations of autologous DCs
      electroporated with mRNA coding for the Wilms' tumor gene 1 (WT1). Safety,
      feasibility and immunogenicity were assessed. RESULTS: Vaccination was feasible
      without toxicity. In an ex vivo antigen re-stimulation assay of peripheral blood
      mononuclear cells, both patients showed increasing cluster of differentiation 137
      (CD137+) antigen-specific T-cells and interleukin 10 (IL-10) production post
      vaccination. Moreover, interleukin-2 (IL-2) production increased (OCS) as well as
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) (SOC).
      Disease in patients progressed after four vaccines and patients continued with
      conventional therapies. After cessation of immunotherapy, they had an extended
      survival of 19 (OCS) and 12 (SOC) months. CONCLUSION: To our knowledge, we report
      for the first time the feasibility and T-cell immunogenicity of WT1 mRNA-loaded
      DC immunotherapy in ovarian cancer.

PMID- 24023320
TI  - Vitamin D favorably alters the cancer promoting prostaglandin cascade.
AB  - BACKGROUND: Preclinical studies suggest that 1,25-dihydroxyvitamin D [1,25(OH)2D]
      and celecoxib inhibit prostaglandins (PGs) associated with cancer through
      different mechanisms. We determined if there was synergy in their use. PATIENTS
      AND METHODS: A total of 36 healthy women received daily for one month/menstrual
      cycle: placebo, 400 international units (IU) vitamin D-3, 2,000 IU vitamin D-3,
      or 2,000 IU vitamin D-3 plus 400 mg celecoxib. Serum and nipple aspirate fluid
      (NAF) were analyzed for PGE2 and transforming growth factor (TGF)beta1 and -2;
      serum for 25(OH)D (total, -D-2, -D-3), plasma for celecoxib; and mammary duct RNA
      for cyclooxygenase (COX)2. RESULTS: 25(OH)D-3 increased (p<0.01) only in the
      groups receiving 2,000 IU vitamin D-3. PGE2 decreased in the breast (p=0.01) only
      after receiving 2,000 IU vitamin D-3; 2,000 IU vitamin D-3 alone was more
      effective in decreasing PGE2 than 2,000 IU vitamin D-3 plus celecoxib (p=0.018).
      COX2 expression decreased only in the breasts of women taking 2,000 IU vitamin D
      3. Change in circulating 25(OH)D-3 correlated with change in TGFbeta2 in the
      breast. CONCLUSION: Vitamin D-3 reduces the PG cascade and increases TGFbeta2 in
      a dose-dependent fashion. Adding celecoxib did not provide synergy.

PMID- 24023321
TI  - Morbid obesity does not disadvantage patients with in situ or early-stage
      carcinoma undergoing breast-conserving surgery.
AB  - AIM: To determine whether morbidly obese (MO) patients with early-stage breast
      cancer (BCa) benefit from standard-of-care interventions. PATIENTS AND METHODS:
      Between 1992 and 2005, 100 patients underwent breast-conserving surgery and
      postoperative whole-breast irradiation of 50 Gy for minimally invasive BCa with
      tumor-free surgical margins. Twenty-seven MO women were compared to 73 non
      morbidly obese (NMO) patients. RESULTS: At 10 years, the cumulative disease-free
      survival rate for the NMO patients was 91% compared to the non-statistically
      significant lower rate of 89% in the MO women (p=0.66). Patients who were
      excessively obese were not at an increased risk for local (p=0.99) or regional
      disease recurrence (p=0.29). CONCLUSION: The results suggest that patients with
      minimally invasive BCa and excessively large body habitus should not be
      disqualified from receiving breast-conserving therapy.

PMID- 24023322
TI  - In vitro demonstration of synergy/additivity between (188)rhenium and sorafenib
      on hepatoma lines: preliminary results.
AB  - BACKGROUND: Hepatocellular carcinoma is generally diagnosed at advanced stages,
      for which only palliative treatments are possible by intra-arterial route or by
      targeted therapies. Among these treatments, metabolic radiotherapy using (90)
      yttrium or (188)Re and sorafenib are two options adopted in monotherapy.
      MATERIALS AND METHODS: We address the question of a possible synergy arising from
      the combination of these two treatments. Two primary malignant hepatoma cell
      lines, N1S1 (murine HCC) and HepG2 (human hepatoblastoma) were treated in media
      containing increasing concentrations of sorafenib with/without (188)Re to assess
      the cellular toxicities of each treatment alone and in combination. The
      combination index method was used to look for synergy or additivity. RESULTS: A
      synergistic advantage of a treatment combining (188)Re and sorafenib is shown in
      vitro on hepatoma cell lines. CONCLUSION: This combined approach is promising and
      now needs to be confirmed by more complex in vitro models integrating the tumoral
      stroma, as well as by in vivo studies.

PMID- 24023323
TI  - Brentuximab vedotin: first-line agent for advanced Hodgkin lymphoma.
AB  - Hodgkin lymphoma (HL) is characterized by malignant Reed-Sternberg cells which
      express CD30. Current National Comprehensive Cancer Network guidelines for
      patients with advanced HL (stage III/IV disease) recommend adriamycin, bleomycin,
      vinblastine, and dacarbazine (ABVD), or escalated bleomycin, etoposide,
      adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP)
      as first-line regimens. ABVD appears to be as effective, with fewer side effects,
      as escalated BEACOPP. Escalated BEACOPP leads to a greater progression-free
      survival but no difference in overall survival. Recent advancements in technology
      have enabled an exciting shift to molecular-targeted cancer therapy. Brentuximab
      vedotin, a CD30-directed antibody conjugate, specifically targets malignant HL
      cells. It is approved by the Food and Drug Administration for the treatment of
      systemic anaplastic large-cell lymphoma and refractory HL that has progressed
      after autologous stem cell transplant, or after two prior multiagent chemotherapy
      regimens among patients ineligible to receive a transplant. 

PMID- 24023324
TI  - Number of involved extracranial organs predicts survival in patients with brain
      metastasis from small cell lung cancer.
AB  - BACKGROUND/AIM: To investigate the prognostic role of the number of involved
      extracranial organs in patients with brain metastasis from small-cell lung cancer
      (SCLC). PATIENTS AND METHODS: Data of 155 patients receiving whole-brain
      radiotherapy (WBRT) alone for brain metastasis from SCLC were retrospectively
      evaluated. In addition to the number of involved extracranial organs, six
      potential prognostic factors were analyzed including WBRT regimen, age, gender,
      Karnofsky performance score (KPS), number of brain metastases, and interval from
      diagnosis of SCLC to WBRT. RESULTS: Six-month survival rates of patients with
      involvement of 0, 1, 2, and >=3 extracranial organs were 52%, 29%, 9%, and 0%,
      respectively (p<0.001). On multivariate analysis, the number of involved
      extracranial organs remained significant (p=0.003). Older age (p=0.005), lower
      KPS (p<0.001), and greater number of brain metastases (p=0.005) were also
      significantly associated with poorer survival. CONCLUSION: The number of involved
      extracranial organs is an independent prognostic factor of survival in SCLC
      patients with brain metastasis.

PMID- 24023325
TI  - Definition of p53 overexpression and its association with the clinicopathological
      features in luminal/HER2-negative breast cancer.
AB  - AIMS: A suitable cut-off value for p53 overexpression and its usefulness as a
      prognostic factor in luminal/HER2-negative breast cancer were evaluated. PATIENTS
      AND METHODS: A retrospective analysis of 1,987 patients with luminal/HER2
      negative breast cancer who underwent surgery between 2001 and 2009 was performed.
      RESULTS: p53 expression >=50% was present in 9% of the patients. Moreover, these
      patients had significantly lower estrogen/progesterone receptor-positive rates,
      higher Ki-67 values, larger tumors, disease-positive nodes, higher nuclear grade,
      and shorter disease-free survival than patients with p53 expression <50%
      (p<0.0001). Therefore, status of p53-positive cells >=50% was classified as p53
      overexpression. These findings indicate that p53 overexpression is associated
      with unfavorable characteristics and prognosis. CONCLUSION: The suitable cut-off
      value for p53 overexpression was determined to be 50%, and p53 overexpression
      appears to be a significant prognostic factor in patients with luminal/HER2
      negative breast cancer.

PMID- 24023326
TI  - Stereotactic radiosurgery plays a critical role in enhancing long-term survival
      in a patient with pancreatic cancer metastatic to the brain.
AB  - BACKGROUND: Pancreatic cancer is an aggressive disease which metastasizes
      readily. The presence of brain metastases from pancreatic cancer is rare and it
      carries a poor prognosis. Our approach to treating these lesions stresses
      extensive use of stereotactic radiosurgery (SRS), whereas other reports focus on
      surgical resection. CASE REPORT: Information regarding the patient's clinical
      history was extracted from a retrospective review of the medical records and
      imaging studies. The patient survived seven years after his primary diagnosis of
      pancreatic cancer, and 36 months after diagnosis of metastatic disease to the
      brain. In addition to surgical resection and the use of multiple chemotherapeutic
      agents, the patient received six separate radiosurgery treatments. CONCLUSION: We
      present a case of brain metastasis from pancreatic cancer that is remarkable for
      an unusually long survivorship and discuss the utility of SRS along with a
      multimodality treatment approach for dealing with these cases.

PMID- 24023327
TI  - Circulating tumor cell (CTC) count and epithelial growth factor receptor
      expression on CTCs as biomarkers for cetuximab efficacy in advanced colorectal
      cancer.
AB  - BACKGROUND/AIM: The purpose of this study was to establish whether CTC count and
      epidermal growth factor receptor (EGFR) expression in CTCs predicted outcome in
      patients with advance colorectal cancer (ACC) receiving cetuximab as third-line
      treatment. PATIENTS AND METHODS: Between October 2008 and March 2011, 63 patients
      with KRAS wild-type ACC were treated with cetuximab-containing chemotherapy at
      the Cancer Institute Hospital. We measured the CTC count and EGFR expression on
      CTCs using the CellSearch System (Veridex LLC, NJ, USA). RESULTS: Nineteen
      patients (30%) with a high number of CTCs had a significantly lower overall
      survival compared with 44 patients with a low number of CTCs. No significant
      difference was observed in progression-free survival between the two groups. Out
      of the 33 patients positive for CTCs (one or more CTC), seven patients (21%) were
      positive for EGFR expression. No statistically significant difference was
      observed in clinical outcome between EGFR-positive and EGFR-negative patients.
      CONCLUSION: A high CTC count predicted reduced overall survival in patients with
      ACC treated with cetuximab-combination chemotherapy as third-line treatment.
      These results suggest that the assessment of CTCs might provide with important
      prognostic information for such patients.

PMID- 24023328
TI  - A rare occurrence of biphasic pulmonary blastoma in an elderly male.
AB  - Pulmonary Blastoma (PB) is a rare primary lung malignancy usually occurring in
      young to middle aged adults. Surgery is the primary mode of treatment, but
      survival is poor with the mean 5-year survival being approximately 16%. We report
      on a case of PB arising in a 63-year-old man. Computed tomography, magnetic
      resonance imaging and positron emission tomography confirmed the mass to be of
      pulmonary origin. The morphological appearance combined with the immunoprofile of
      the tumour was consistent with a poorly-differentiated biphasic pulmonary
      blastoma. Two months after the surgical resection the patient relapsed with
      multiple sites of metastasis. The patient was treated with four cycles of
      cyclophosphamide-, doxorubicin- and vincristine-(CAV)-based chemotherapy,
      achieving a partial response to treatment. He is currently on a two-monthly
      review and is recovering from chemotherapy-related toxicities. 

PMID- 24023329
TI  - Incidence of bisphosphonate-related osteonecrosis of the jaw in consideration of
      primary diseases and concomitant therapies.
AB  - BACKGROUND: Since its first description by Marx in 2003, the etiology of
      bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the subject of
      numerous scientific discussions for oral and maxillofacial surgeons. Many
      retrospective studies on its etiology and pathogenesis have been carried out to
      explain pathological mechanisms; most of them just take a close look at the issue
      of dosage and application. Recently, attempts have been made, to identify co
      factors which might promote the development of BRONJ. PATIENTS AND METHODS: The
      present study is based on data of 169 patients with osseous metastatic
      malignancies. All patients received intravenous bisphosphonate therapy. On the
      basis of medical history, malignancy, and primary treatment, the modality of
      bisphosphonate therapy, and existing comorbidities and medication were analyzed.
      The role of immunosuppressive drugs, influence of underlying diseases, and
      general factors such as age and gender were examined. The predictability of
      necrotic involvement, influenced by the underlying malignancy and its specific
      therapy, e.g. radiation and cytostatic therapy were analyzed and statistically
      evaluated. RESULTS: A total of 8.9% (n=15) of patients developed BRONJ. The
      average time between diagnosis of malignancy and BRONJ was 80 months. Nine
      patients suffered from breast cancer, five had prostate cancer and one renal
      cancer. Separation into stage and histological subtype did not show any
      significant correlation, nor did age or gender, to the occurrence of BRONJ.
      However statistical analysis did show a significant correlation concerning
      monocytostatic (p=0.0215) and triple-cytostatic therapy (p=0.0137). The majority
      of patients with BRONJ (60%) received a bisphosphonate therapy including
      zoledronate. Single application with one bisphosphonate was administered in 28
      cases; 44 patients had a medical history of different use of bisphosphonate.
      Concomitant medication did not suggest possible correlation, nor did accompanying
      diseases, arterial hypertension (33.33%) or arterial microcirculatory
      disturbances (20%). CONCLUSION: The evaluation of our results is pioneering. The
      influence of cytostatics and combined therapy of cytotoxic drugs on the
      pathogenesis of BRONJ is demonstrated here statistically. We confirmed a drug-
      and dose-dependent occurrence of BRONJ. Further prospective studies should be
      performed to elucidate the role of tissue perfusion and oxygen saturation, and
      the influence of immunosuppressive drugs in relation to the occurrence of BRONJ,
      as well as on wound healing of initial lesions.

PMID- 24023330
TI  - Prediction of nodal metastasis and prognosis of breast cancer by ANN-based
      assessment of tumour size and p53, Ki-67 and steroid receptor expression.
AB  - BACKGROUND: Tumour stage and the appropriate course of treatment in patients with
      breast cancer are primarily characterized by the state of metastasis in the
      axillary lymph nodes. In recent years, substantial research has focused on the
      prediction of lymph node status based on various pathological and molecular
      markers in order to obviate the necessity to carry out axillary dissection. In
      the present study, artificial neural network (ANN) is employed as the analysis
      platform to examine the prognostic significance of a group of well-established
      prognostic markers for breast cancer outcome prediction in terms of nodal status.
      Furthermore, we investigated existing interactions between these markers.
      PATIENTS AND METHODS: The data set contained 66 patient records, where 5
      pathological and molecular markers including tumour size, oestrogen receptor
      status (ER), progesterone receptor status (PR), Ki-67 and p53 expression had been
      assessed for each patient. The spread of metastasis to the axillary lymph nodes
      was clinically diagnosed and patients were accordingly categorized into node
      positive and node-negative groups. The aforementioned markers were analyzed using
      a probabilistic neural network (PNN) for nodal status prediction which was
      considered as the network output. Furthermore, the interactions between these
      markers were evaluated using different marker combinations as the network input
      for finding the best marker arrangement for nodal predication. RESULTS: The best
      prediction accuracy was obtained by a 3-marker combination including tumour size,
      PR and p53 with 71% accuracy for nodal prediction. Leaving out ER and PR from the
      full marker set showed approximately the same variations in the results, which is
      an indication of the direct correlation of these two markers. Furthermore, tumour
      size was proved to be the most significant individual marker for predicting nodal
      metastasis. However, when used in combination with Ki-67 the prediction results
      drop significantly. CONCLUSION: The results presented here indicate that
      molecular and pathological markers can provide useful information for early-stage
      prognosis. However, the interactions between these markers must be considered in
      order to achieve accurate and reliable prediction.

PMID- 24023331
TI  - The surgeon as the most important factor in lymph node harvest during axillary
      clearance.
AB  - BACKGROUND: Current guidelines state that 10 or more lymph nodes (LNs) must be
      harvested in over 90% of axillary lymph node dissections (ALND), with the
      implication that 'more is better' during axillary surgery. PATIENTS AND METHODS:
      Our study included all consecutive patients from April 2010 - August 2011 at an
      NHS Trust (UK) who underwent ALND with the intention of clearing the axilla of
      LNs (level III). Data regarding harvested LNs were recorded in electronic patient
      records for each ALND operation. The names of the surgeon and reporting
      histopathologist were recorded, as well as data regarding preoperative
      neoadjuvant chemotherapy, prior sentinel lymph node biopsy (SLNB), and number of
      metastatic LNs. Statistical significance for continuous data was evaluated using
      unpaired t-test. Pearson correlation coefficient was used to assess the
      relationship between total number of LNs harvested and number of metastatic LNs.
      RESULTS: A total of 232 patients underwent 237 ALND operations; 5/232 (2.2%)
      underwent bilateral surgery. The mean age (range) was 59.9 (32-94) years; the
      mean number of LNs (range) excised was 13.1 (0-35). The number of identified LNs
      was independent of whether the patient had undergone previous SLNB, or had
      received neoadjuvant chemotherapy. The number of LNs was independent of the
      histopathologist; however, there was a significant difference between surgeons
      (p<0.001). There was no statistically significant correlation between the total
      number of LNs harvested and the number of metastatic LNs harvested (r=0.301;
      p=0.297). CONCLUSION: When auditing practice against guidelines for the treatment
      of the axilla in breast cancer, the surgeon undertaking ALND appears to be the
      only significant variable in affecting the completeness of dissection. However,
      the number of nodes harvested is unrelated to the number of metastatic nodes,
      challenging the idea that 'more is better' when it comes to axillary surgery.

PMID- 24023332
TI  - Impact of chemotherapy with S-1 and oxaliplatin (SOX) in combination with
      molecular-targeting agents on colorectal liver metastases.
AB  - AIM: The aim of this study was to evaluate the impact of chemotherapy with
      molecular-targeting agents on liver metastases from colorectal cancer. PATIENTS
      AND METHODS: Six patients with synchronous colorectal liver metastases who
      underwent hepatectomy after chemotherapy with S-1 and oxaliplatin (SOX) between
      January 2010 and December 2011 at the Department of Surgery, Kashiwa Hospital,
      the Jikei University School of Medicine were enrolled. Two patients received only
      SOX as chemotherapy, while the others received SOX in combination with one of the
      three molecular-targeting agents, bevacizumab, cetuximab, and panitumumab.
      RESULTS: In the two patients who received SOX alone, liver metastases completely
      disappeared at more than six months after starting chemotherapy as shown by
      computed tomographic (CT) scan. However, malignant cells were diffusely detected
      by pathological examination at the site of liver metastases, as detected by CT
      scan before chemotherapy. In the other four patients who received SOX in
      combination with molecular targets, the size of liver metastases appeared
      unchanged at three months after limited chemotherapy by CT scan. Pathologically,
      few malignant cells were detected, only at the borderline of the tumor, while
      most tumor cells inside the tumor were necrotized and been replaced by
      fibroconnective tissue. CONCLUSION: Molecular-targeting agents may induce tumor
      necrosis rapidly from inside the tumor, which might not be detected by CT scan
      before surgery.

PMID- 24023333
TI  - A high serum uric acid level is associated with poor prognosis in patients with
      acute myeloid leukemia.
AB  - Uric acid in serum (S-UA) is produced by the breakdown of the cellular nucleic
      acids of leukemia cells, and may be a marker of disease aggressiveness. S-UA
      levels were examined for association with clinical outcomes in patients with
      acute myeloid leukemia (AML). Fifty-six patients with AML admitted to our
      Institution were evaluated retrospectively. The median S-UA level at diagnosis
      was 5.0 mg/dl (range 2-13.8 mg/dl). The S-UA levels did not correlate with
      peripheral lactate dehydrogenase, peripheral white blood cell counts, or
      peripheral blast counts, and were not proportional to bone marrow blast counts or
      marrow cellularity. The S-UA levels in the patients who achieved complete
      remission were slightly lower than those in those who did not. S-UA levels less
      than, or equal to the median (5.0 mg/dl) were significantly associated with
      better prognoses, compared with S-UA levels greater than 5.0 mg/dl. Thus, the S
      UA level may predict the prognosis of AML, and is a versatile and cost-effective
      test for such a purpose. 

PMID- 24023334
TI  - Prognostic value of nuclear translocation of aryl hydrocarbon receptor for non
      small cell lung cancer.
AB  - BACKGROUND: The aryl hydrocarbon receptor (AhR) is a ligand-activated
      transcription factor which translocates from the cytoplasm to the nucleus after
      activation. AhR overexpression is positively associated with epidermal growth
      factor (EGFR) expression in non-small cell lung cancer (NSCLC). The association
      between AhR expression and types of EGFR mutation, and the prognostic value of
      AhR expression in NSCLC remain unclear. PATIENTS AND METHODS: The AhR expression
      and detection of L858R and E746-750A deletion of EGFR in NSCLC was assessed using
      immunohistochemistry. RESULTS: Nuclear translocation of AhR was more common in
      females, non-smokers, adenocarcinoma (AD) and NSCLC patients with EGFR E746-750A
      deletion. The overall median survival time (MST) was 20.4 months for patients
      with NSCLC, 21.8 months for these with AD and 15.4 months for these with squamous
      cell carcinoma (SQ). The MST was significantly reduced in patients with poor
      performance status, SQ or advanced cancer stage. AhR nuclear translocation was
      associated with cancer death in SQ (hazard ratio=3.714, p<0.001) but not in AD
      (hazard ratio=0.837, p=0.407). CONCLUSION: Nuclear translocation of AhR was
      associated with EGFR mutation, and conferred a poor prognosis for patients with
      lung SQ.

PMID- 24023335
TI  - Comparisons of late vaginal mucosal reactions between interstitial and
      conventional intracavitary brachytherapy in patients with gynecological cancer:
      speculation on the relation between pallor reaction and stenosis.
AB  - BACKGROUND/AIM: To examine late vaginal mucosal reactions in patients following
      interstitial brachytherapy (ISBT) compared with that of intracavitary
      brachytherapy (ICBT). PATIENTS AND METHODS: We introduced a modified Dische score
      to examine late reactions in vaginal mucosa of patients with gynecological cancer
      who underwent vaginal brachytherapy at 6, 12, 18, 24, 36, and 60 months after
      treatment. A comparison was made between patients who underwent ISBT (n=37) and
      those under conventional ICBT (n=63) with a median follow-up time of 41 months.
      The ICBT group included only patients with newly diagnosed cervical cancer,
      whereas the ISBT group included 17 patients with recurrent and 20 with newly
      diagnosed cancer. RESULTS: Grade 1 reactions of bleeding and discharge were
      exhibited by <12% of patients. Erythema was detected in approximately 30% (mainly
      grade 1) of the patients. A total of two (3%) patients developed superficial
      ulceration after ICBT, whereas three (8%) grade 1 ulcers were detected in
      patients after ISBT. Telangiectasias were detected in approximately 70% (60%
      grade 1 and 10% grade 2) of patients. No statistically significant difference was
      found between the patients after ISBT and ICBT. After ISBT, patients have a
      higher stenosis rate than after ICBT (p=0.003). The pallor scores showed a strong
      correlation with stenosis (p<0.0001) and were higher in patients after ICBT than
      in patients after ISBT (p=0.006). CONCLUSION: After ISBT, patients exhibited
      milder but similar late mucosal reactions compared to those after ICBT, except
      the fact that the stenosis was more severe and the pallor reaction was milder in
      these patients. It can be, therefore, concluded that the pallor reaction is
      related to stenosis.

PMID- 24023336
TI  - Podoplanin and VEGF-C immunoexpression in oral squamous cell carcinomas:
      prognostic significance.
AB  - BACKGROUND: This study evaluated the clinical significance of podoplanin and
      vascular endothelial growth factor-C (VEGF-C) expression in oral squamous cell
      carcinoma (OSCC). PATIENTS AND METHODS: The immunohistochemical expression of
      podoplanin and VEGF-C were investigated in 42 well-differentiated OSCCs. The Chi
      square test was used to analyze the association of biomarker expression with the
      clinical characteristics, treatment, and outcome, as well as with
      histopathological microscopic features and histopathological malignancy index.
      The relationship between podoplanin, VEGF-C and prognosis was also studied.
      Survival rates were calculated by the Kaplan Meier method. RESULTS: Strong
      podoplanin expression was associated with male gender (p=0.037) and with early
      clinical stage (I-II) (p=0.027). Strong podoplanin expression was more frequently
      found in patients with perineural infiltration. Podoplanin and VEGF-C expression
      were not significant prognostic factors for patients with OSCC. CONCLUSION: These
      results suggest that the strong podoplanin and VEGF-C expression by malignant
      cells is associated with perineural invasion in patients with OSCC.

PMID- 24023337
TI  - Microsatellite instability analysis for the screening of synchronous endometrial
      and ovarian cancer in Lynch syndrome.
AB  - We report on a case of synchronous endometrial and ovarian cancer in a patient
      with Lynch syndrome. An endometrial biopsy performed during routine screening
      revealed microsatellite instability (MSI) and loss of expression of human mutL
      homolog-1 (MLH1) and postmeiotic segregation increased-2 (PMS2) in a setting of
      complex hyperplasia. Whereas gynaecological screening including clinical
      examination, pelvic ultrasound, and endometrial biopsy, has not proven its
      benefit, our case report points out the place of MSI analysis and
      immunohistochemical investigation of mismatch repair protein expression in
      endometrial samples during gynaecological screening. 

PMID- 24023338
TI  - TXNDC5 gene polymorphism contributes to increased risk of hepatocellular
      carcinoma in the Korean male population.
AB  - Thioredoxin domain-containing protein-5 (TXNDC5) has been found to be associated
      with cancer development and growth. We investigated whether TXNDC5 gene
      polymorphisms are associated with hepatocellular carcinoma (HCC) in a Korean male
      population. Seven SNPs were selected based on minor allelic frequency (>=5%). The
      SNPs consisted of three exonic SNPs (rs8643, rs7764128 and rs1043784) and four
      intronic SNPs (rs1225944, rs1225943, rs1225945 and rs1225958). We selected and
      assessed these SNPs in 160 patients with HCC and 178 controls. Genetic data were
      analyzed using SNPAnalyzer Pro, SNPStats, and Haploview programs. Two SNPs of the
      TXNDC5 gene were found to be associated with the risk of HCC development. The
      genotypic frequency of rs1225944 was associated with HCC in the recessive model
      [CC/CT vs. TT, p=0.43, Fisher's exact test p=0.032; odds ratio (OR)=0.54, 95%
      confidence interval (CI)=0.11-2.71]. The genotypic frequency of rs1225943 was
      associated with HCC in the co-dominant 2 (AA vs. CC, p=0.07; Fisher's exact test
      p=0.001, OR=0.23, 95% CI=0.05-1.10), recessive (AA/AC vs. CC, p=0.044, Fisher's
      exact test p=0.001, OR=0.25, 95% CI=0.05-1.17), and log-additive models (p=0.08,
      Fisher's exact test p=0.002, OR=0.68, 95% CI=0.44-1.05). The haplotype CA and TC
      of rs1229544 and rs1225943, demonstrated a significant association with HCC. Our
      results suggest that TXNDC5 polymorphisms could be related to the development of
      HCC in the Korean male population. 

PMID- 24023339
TI  - Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients
      with peritoneal sarcomatosis: long-term outcome from a single institution
      experience.
AB  - AIM: We assessed the long-term local disease-free survival (LDFS) and overall
      survival (OS) of patients with peritoneal sarcomatosis (PS) uniformly-treated
      with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS plus
      HIPEC). PATIENTS AND METHODS: Retrospective data of 15 patients who underwent CS
      plus HIPEC for PS were extracted from a prospectively collected database. DFS and
      OS were calculated from the date of CS plus HIPEC to local relapse and death,
      respectively. RESULTS: After a median follow-up of 28 months (range=4-144
      months), median LDFS was 15 months (95% Confidence Interval CI=1-40 months).
      Median OS was 27 (95% CI=24.7-29.3) months. Long-term OS was achieved in three
      patients (20%) and ranged between 93 and 144 months. Female sex was the only
      factor significantly correlated with a greater LDFS (p=0.018). Patients with PS
      of visceral origin seem at lower risk of recurrence and death but the difference
      did not prove significant. CONCLUSION: In our series, long-term survival was
      achieved in 20% of patients after CS plus HIPEC, with a benefit in female
      patients with PS of visceral origin. The impact of HIPEC after radical surgery
      for PS remains questionable and still has to be further evaluated in large
      cooperative multi-institutional studies.

PMID- 24023340
TI  - Influence of age on short-term complications after intraoperative radiotherapy in
      women after breast-conserving surgery.
AB  - BACKGROUND: We investigated the influence of age on short-term complications in
      women undergoing intraoperative radiotherapy (IORT) for early breast cancer.
      PATIENTS AND METHODS: We retrospectively analyzed data of 188 women who underwent
      IORT during breast-conserving surgery (BCS). The study group consisted of 54
      patients aged 70 years or older. One hundred and thirty four patients aged less
      than 70 years served as the control group. RESULTS: In both collectives, the
      acute toxicity was low. There were no significant differences regarding type and
      duration of surgery, and type of radiation treatment, comparing both collectives.
      The most frequent postoperative side-effects were haematoma/suggillation (13/54,
      24.1% vs. 28/134, 20.9%; p=0.633). There was a significantly higher incidence of
      postoperative axillary haematoma in the study group (10/54, 18.5% vs. 10/134,
      7.5%; p=0.026). CONCLUSION: Acute toxicity after BCS with IORT in women aged 70
      years and older does not seem to be higher compared to younger patients.

PMID- 24023341
TI  - Pancreatic neuroendocrine tumor with ectopic adrenocorticotropin production: a
      case report and review of literature.
AB  - Pancreatic neuroendocrine tumors (p-NETs) entail a vast array of tumors, which
      can vary from benign neoplastic growths to rapidly aggressive malignancies. Such
      is the case with ectopic adrenocorticotropic hormone (ACTH)-producing p-NETs.
      These tumors have been found to be quite aggressive and a challenge to treat,
      especially due to the occurrence of metastatic disease even after resection of
      the primary tumor. We discuss the case of a 44-year-old female who initially
      presented with vague, non-specific symptoms, in which a malignant p-NET was found
      to be the cause of her clinical presentation. Although resection of the
      pancreatic mass was performed, the patient presented again with metastatic
      disease to the liver. 

PMID- 24023342
TI  - E6/E7 mRNA expression of high-risk HPV types in 849 Greek women.
AB  - AIM: The goal of this study was to investigate human papillomavirus (HPV) geno
      typing and high-risk HPV E6/E7 mRNA expression in 849 women. PATIENTS AND
      METHODS: 849 Cervical samples were obtained from patients attending an outpatient
      clinic to have their annual gynaecological check-up. All patients underwent a
      conventional Pap test. The patients were also offered HPV test with the knowledge
      that it is not part of the screening. RESULTS: Overall prevalence of HPV DNA was
      41.3%, while E6/E7 mRNA expression was found in 20.7% of the patients. HPV DNA
      and E6/E7 mRNA expression were detected in 21.1% and 9.1% of normal cytological
      samples, respectively, 38.1% and 23.8% of atypical squamous cells of unknown
      significance, 84.8% and 40.7% of low-grade squamous intraepithelial lesions, and
      96.4% and 89.3% of high-grade squamous intraepithelial lesions, respectively. HPV
      16 was the most frequent genotype identified. CONCLUSION: E6/E7mRNA detection
      might be useful as a screening marker for the early prediction of active
      infections and subsequent progression to severe dysplasia.

PMID- 24023343
TI  - Low-dose fotemustine as second-line chemotherapy for recurrent glioblastoma
      multiforme.
AB  - AIM: To test if fotemustine administrated at low doses during the maintenance
      phase of gioblastoma therapy could improve the toxicity profile, without reducing
      progression-free survival at six months (PFS-6). PATIENTS AND METHODS: Patients
      enrolled were affected by recurrent glioblastoma multiforme, proven by magnetic
      resonance imaging (MRI), at least six months after radiochemotherapy completion.
      Fotemustine was administered at an induction dose of 100 mg/m(2) followed by a
      maintenance dose of 75 mg/m(2). RESULTS: All 15 patients completed the induction
      phase. Eight patients began maintenance-phase therapy and received a median of
      three cycles (range=2-6). Grade 3 or more haematological toxicity was not
      documented. The PFS-6 was 5/15 and the median overall survival was 7.5 months.
      CONCLUSION: Haematological toxicity compares favourably with trials using the
      conventional scheme: no grade 3-4 adverse effects were recorded. This low-dose
      approach could be considered a compromise treatment whilst waiting for definitive
      standardization of second-line therapy, in order to reduce severe hematological
      toxicity.

PMID- 24023344
TI  - Water swallow screening test for patients after surgery for head and neck cancer:
      early identification of dysphagia, aspiration and limitations of oral intake.
AB  - Patients with head and neck cancer (HNC) are at high risk for oropharyngeal
      dysphagia (OD) following surgical therapy. Early identification of OD can improve
      outcomes and reduce economic burden. This study aimed to evaluate the validity of
      a water screening test using increasing volumes postsurgically for patients with
      HNC (N=80) regarding the early identification of OD in general, and whether there
      is a need for further instrumental diagnostics to investigate the presence of
      aspiration as well as to determine the limitations of oral intake as defined by
      fiberoptic endoscopic evaluation of swallowing. OD in general was identified in
      65%, with aspiration in 49%, silent aspiration in 21% and limitations of oral
      intake in 56%. Despite a good sensitivity, for aspiration of 100% and for
      limitations of oral intake of 97.8%, the presented water screening test did not
      satisfactorily predict either of these reference criteria due to its low positive
      likelihood ratio (aspiration=2.6; limitations of oral intake=3.1). However, it is
      an accurate tool for the early identification of OD in general, with a
      sensitivity of 96.2% and a positive likelihood ratio of 5.4 in patients after
      surgery for HNC. 

PMID- 24023345
TI  - Clinical influence of endoscopic resection on subsequent laparoscopic gastrectomy
      for gastric cancer.
AB  - BACKGROUND: Endoscopic resection (ER) causes inflammation, edema, fibrosis of the
      stomach, and severe adhesions around the surrounding tissue. However, little is
      known about the clinical influence of ER on subsequent laparoscopic gastrectomy
      (LG) for gastric cancer. PATIENTS AND METHODS: Between October 2007 and April
      2011, 202 consecutive patients underwent curative LG for gastric cancer. Out of
      these, 30 (15%) LG cases had previously undergone ER and further LG to achieve a
      cure. The remaining 172 patients (85%) had no history of ER. We reviewed their
      hospital records retrospectively. RESULTS: Intraperitoneal adhesions were
      detected in all patients after ER. However, there were no significant differences
      in clinical outcome, such as surgical duration, blood loss, number of dissected
      lymph nodes, complications, or hospital stay, between LG cases with and those
      without previous ER. Of the 30 cases of LG with previous ER, 15 treated within
      two months after ER had greater blood loss (p<0.005) and a longer surgical
      duration (p=0.06). LG cases with major or minor perforation during ER also had
      slightly greater blood loss (p=0.07) than those without. However, the number of
      dissected lymph nodes associated with surgical curability and postoperative
      complications were not significantly different in patients with and those without
      these clinical factors. CONCLUSION: LG can be performed curatively and safely
      even after ER. Perforation during ER and shorter time to LG after ER may be
      potential risks of surgical difficulty in subsequent LG.

PMID- 24023346
TI  - Feasibility study of oxaliplatin with oral S-1 or capecitabine as first-line
      therapy for patients with metastases from colorectal cancer.
AB  - BACKGROUND/AIM: The aim of this study was to determine the feasibility of S-1
      plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (XELOX) as first-line
      therapy for patients with initially unresectable metastases from colorectal
      cancer. PATIENTS AND METHODS: Fourteen patients with colorectal cancer who
      underwent elective colorectal resection between January 2009 and December 2010 at
      the Department of Surgery, Kashiwa Hospital, the Jikei University School of
      Medicine, with initially unresectable metastatic lesions were enrolled in this
      study. After curative resection for the primary colorectal cancer, they underwent
      adjuvant chemotherapy with SOX or XELOX, starting at one month after surgery.
      RESULTS: Seven patients (50%) received SOX, and the others received XELOX as
      first-line therapy for initially unresectable metastases from colorectal cancer.
      Four (29%) patients had complete response for liver metastases over six months
      after chemotherapy, and liver metastases were subsequently judged to be
      completely resected by surgery. For the other ten patients, the median
      progression-free survival was 9.1 months and median overall survival was 24.1
      months. There were no patients with grade 3 or 4 adverse reactions throughout the
      entire chemotherapy. CONCLUSION: Oxaliplatin with oral S-1 or capecitabine as
      first-line therapy for patients with initially unresectable metastases from
      colorectal cancer is safe and feasible.

PMID- 24023347
TI  - Effect of thrombosis-related gene polymorphisms upon oral cancer: a regression
      analysis.
AB  - It is well-known that there is an interplay between hemostasis, thrombosis and
      cancer. Functional DNA polymorphisms in genes encoding factors related to
      thrombosis have been associated with increased risk for oral squamous cell
      carcinoma (OSCC). The present study investigated the possible combinatory effect
      of 10 such polymorphisms as primary risk predictors for OSCC in a European
      population. Two groups including 160 patients with OSCC and 168 healthy controls
      of Greek and German origin were studied. The patient and control groups were
      comparable regarding ethnicity, age and gender. For all studied individuals, 10
      genotypes of functional polymorphisms were investigated: 5,10-methylene
      tetrahydrofolate reductase (MTHFR) C677T, coagulation factor V (F5) Leiden,
      coagulation factor II (F2, also known as prothrombin) G20210A, coagulation factor
      XII (F12) C46T, coagulation factor XIII A1 subunit (F13A1) Val34Leu, serpine1
      (SERPINE1, also known as plasminogen activator inhibitor-1) 4G/5G, protein Z
      (PROZ) -A13G, angiotensin I-converting enzyme (ACE) I/D, angiotensinogen (AGT)
      Met325Thr, and carboxypeptidase B2 (CPB2, also known as thrombin-activatable
      fibrinolysis inhibitor) C1040T. Multivariate logistic regression models were used
      in order to evaluate the relation and contribution of homozygous and heterozygous
      variant polymorphisms upon overall, early and advanced stages of OSCC. Five out
      of the studied polymorphisms, influencing the expression of SERPINE1 and ACE
      genes, as well as the activity of CPB2, F12 and F13 proteins, were recognized as
      significant predictive factors for OSCC. The 'mode of inheritance' regression
      model, in particular, revealed the low expression I allele of ACE to be a primary
      predictor in overall, early and advanced stages of oral cancer. Comparing the
      present findings with previous knowledge, possible interactions of these factors
      and their relation to the risk for OSCC development are discussed. 

PMID- 24023348
TI  - Negative impact of fresh-frozen plasma transfusion on prognosis of pancreatic
      ductal adenocarcinoma after pancreatic resection.
AB  - BACKGROUND: Excessive blood loss and blood transfusion may influence
      postoperative complications and prognosis of patients after pancreatic resection.
      We evaluated the influence of blood products use on postoperative recurrence and
      outcome of patients with pancreatic ductal adenocarcinoma. PATIENTS AND METHODS:
      The study included 82 patients who underwent elective pancreatic resections for
      pancreatic ductal adenocarcinoma without distant metastasis or other malignancies
      between January 2001 and December 2010. We retrospectively investigated the
      influence of the use of perioperative blood products including red cell
      concentrate, fresh-frozen plasma (FFP), and albumin preparation, and clinical
      variables regarding disease-free and overall survival. RESULTS: In disease-free
      survival, serum carcinoembryonic antigen more than 10 ng/ml (p=0.015), serum
      carbohydrate antigen 19-9 (CA19-9) more than 200 U/ml (p=0.0032), R1 resection
      (p=0.005), and FFP transfusion were independent risk factors for cancer
      recurrence in the Cox proportional regression model, pancreaticoduodenectomy
      (p=0.057) and advanced tumor stage (p=0.083) tended to associate with poor
      disease-free survival, but were not statistically significant. In overall
      survival, male gender (p=0.012), advanced tumor stage (p=0.005), serum CA19-9
      more than 200 U/ml (p<0.001), and FFP transfusion (p=0.003) were positively
      associated with poor overall survival in the Cox proportional regression model.
      CONCLUSION: FFP transfusion is associated with poor therapeutic outcome after
      elective pancreatic resection for pancreatic ductal adenocarcinoma.

PMID- 24023349
TI  - Genetic profile and determinants of homocysteine levels in Kazakhstan patients
      with breast cancer.
AB  - AIM: To analyze associations between homocysteine level, MTHFR and FTO rs1477196
      polymorphisms and folate status in patients with breast cancer (BC) in order to
      clarify determinants of hyperhomocysteinemia. PATIENTS AND METHODS: The study
      included 315 BC cases and 604 controls. RESULTS: The MTHFRC677T genotype was
      associated with an increased incidence of BC [Odds ratio (OR)=1.71; 95%
      Confidential interval (CI)=1.21-2.43]. The MTHFR A1298C genotype was associated
      with a decreased risk of BC [OR=0.68; 95% CI: 0.49-0.95]. The homocysteine level
      was not associated with either MTHFR C677T or A1298C, nor with FTO rs1477196, but
      was inversely correlated with folate status in cancer cases (p<0.0001) and tended
      to be higher in patients with the MTHFR 677TT genotype. The folate level
      (p<0.0005) was an independent predictor of hyper-homocysteinemia in patients with
      BC. CONCLUSION: These results suggest an important role of homocysteine in breast
      tumorigenesis. Further studies are warranted to investigate how combined MTHFR
      genotypes exert their effects on cancer susceptibility.

PMID- 24023350
TI  - Bevacizumab as front-line treatment of brain metastases from solid tumors: a case
      series.
AB  - BACKGROUND: Despite the large use of bevabizumab in the treatment of primary
      tumors of the brain, there is only limited experience with brain metastases (BM)
      and no experience in the treatment of previously untreated secondary brain
      lesions. PATIENTS AND METHODS: We treated patients with BM, not suitable for
      local treatment, with a bevacizumab-based therapy associated with chemotherapy or
      interferon-alpha, as indicated for the primary cancer type. RESULTS: We studied
      18 patients with BM mostly from lung and renal adenocarcinoma, and the majority
      of patients had a treatment-naive brain disease. Bevacizumab was found to be
      effective: the response rate was 60% partial responses with 40% disease
      stabilizations. The progression-free survival was 14 months and the overall
      survival was 15 months. Moreover, bevacizumab has a high capability of providing
      a long-lasting clinical benefit and reducing edema. CONCLUSION: Bevacizumab for
      treatment of BM is feasible and the efficacy data are very encouraging.

PMID- 24023351
TI  - Effects of ataxia telangiectasia mutated (ATM) genotypes and smoking habits on
      lung cancer risk in Taiwan.
AB  - AIM: The study aimed to evaluate the association and interaction of ataxia
      telangiectasia mutated (ATM) genetic polymorphisms with lung cancer risk in
      Taiwan, where lung cancer is the primary cause of cancer-related death. MATERIALS
      AND METHODS: In this hospital-based matched case-control study, associations of
      up to seven ATM single nucleotide polymorphisms (rs600931, rs652311, rs227060,
      rs228589, rs227092, rs624366 and rs189037) with lung cancer risk were
      investigated among Taiwanese. In this study, 358 lung cancer patients and 716 age
      and gender-matched healthy controls were genotyped and the genetic-lifestyle
      interaction were analyzed. RESULTS: The results showed that the percentages of
      GG, AG and AA for ATM rs652311 genotypes were significantly different at 34.6%,
      48.9% and 16.5% in the lung cancer patient group and 39.9%, 51.0% and 9.1% in non
      cancer control group, respectively. We further analyzed the genetic-lifestyle
      effects on lung cancer risk and found that the contribution of ATM rs652311 A
      allele-bearing genotypes to lung cancer susceptibility was enhanced in the
      cigarette smokers and not enhanced in the non-smokers (p=0.0045 and 0.2758,
      respectively). CONCLUSION: Our results provide evidence that the A allele of ATM
      rs652311 may be associated with lung cancer risk, and may enhance the effects of
      smoking habit on lung cancer development.

PMID- 24023352
TI  - Phosphorylated S6 kinase-1: a breast cancer marker predicting resistance to
      neoadjuvant chemotherapy.
AB  - BACKGROUND: Pre-clinical data support a link between the phosphatidylinositol 3
      kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)
      signaling pathway and chemoresponsiveness. We evaluated whether the expression of
      phosphorylated AKT (p-AKT) or phosphorylated S6 kinase-1 (p-S6K1), a key effector
      of the mTOR pathway, could be a predictive marker for chemoresponsiveness in
      breast cancer. PATIENTS AND METHODS: A total of 209 patients with locally
      advanced breast cancer who received neoadjuvant chemotherapy between April 2005
      and July 2012 were analyzed. Patients without a minimum of 10% tumor reduction,
      after neoadjuvent chemotherapy, were classified as non-responders. RESULTS:
      Overall, 184 (88%) patients were classified as responders and 25 (12%) as non
      responders. The positive expression rate for p-AKT and p-S6K1 was 31.6% and 45%,
      respectively. There was no difference in the pre-chemotherapy clinical stage
      according to p-S6K1 or p-AKT expression status. p-AKT expression was slightly
      higher in non-responders compared to responders (48% vs. 30.9%; p=0.088).
      However, p-S6K1 expression was significantly higher in non-responders than
      responders (68% vs. 41.8%; p=0014). Following multivariate analysis, p-S6K1
      positivity remained an independent predictor of non-responder status (hazard
      ratio=3.81; 95% confidence interval=1.28-11.31; p=0.016). CONCLUSION: The
      expression of p-S6K1 may be a predictive marker of resistance to neoadjuvant
      chemotherapy in patients with breast cancer.

PMID- 24023353
TI  - Patient outcome after complete surgery for retroperitoneal sarcoma.
AB  - BACKGROUND: Aggressive surgery has been suggested for improving local tumor
      control in patients with retroperitoneal sarcoma (RS). This study aimed at
      investigating local disease-free and overall survival after complete surgery, in
      patients with RS. PATIENTS AND METHODS: Retrospective data of patients submitted
      to complete surgery for RS were extracted from a prospectively-maintained
      database. RESULTS: Forty-three out of 78 patients (55%) presented with primary
      RS. Infiltrated organs were resected in 42 patients (54%). Patients presenting
      with recurrent (hazard ratio (HR)=5.57, p=0.002) and high-grade (HR 3.47,
      p=0.041) tumors were at higher risk of local recurrence. Microscopically-involved
      tumor resection margins (HR=3.47, p=0.04) and recurrent tumor at presentation
      (HR=2.49, p=0.008) were independent predictors of poor survival. CONCLUSION:
      Patients presenting with primary RS had longer local disease-free survival and
      overall survival than those with recurrent tumor after complete surgery. Complete
      surgery remains the standard-of-care for patients with primary RS.

PMID- 24023354
TI  - Gemcitabine and capecitabine as third- or later-line therapy for refractory
      advanced colorectal cancer: a retrospective study.
AB  - AIM: To evaluate gemcitabine plus capecitabine as third-line or later-line
      therapy in patients with refractory advanced colorectal cancer (CRC) who maintain
      a good performance status (PS). PATIENTS AND METHODS: We retrospectively
      evaluated patients who had failed at least two lines of therapy or had
      contraindication to standard therapy and received gemcitabine (1,000 mg/m(2), d1
      biweekly) plus capecitabine (1,700 mg/m(2)/day, d1-7 every two weeks) in a
      compassionate use program. RESULTS: Thirty-nine patients were enrolled. The
      majority (85%) had ECOG PS 1. Gemcitabine plus capecitabine was administered as
      third- and fourth-line in 49% and 23% of patients, respectively; and as fifth
      line or later-line in 28%. A clinical benefit of 21% was found. The median
      progression-free survival and overall survival were 3.0 and 7.3 months,
      respectively. Toxicity was mild to moderate, with no reported grade 4 toxicities.
      CONCLUSION: Gemcitabine plus capecitabine was safe and well-tolerated. While the
      efficacy of this regimen was modest in terms of response, the survival data were
      acceptable and consistent with previous publications on this setting.

PMID- 24023355
TI  - Urinary neopterin concentration and toxicity of radiotherapy in patients with
      head and neck carcinoma during external beam radiation.
AB  - AIM: Increased serum or urinary concentrations of neopterin are predictive of
      poor prognosis in patients with tumors across a spectrum of primary locations.
      Less information is available about the significance of changes of urinary
      neopterin concentrations during therapy. The aim of the present study was to
      examine the association between urinary neopterin and toxicity of radiotherapy.
      PATIENTS AND METHODS: We analyzed changes of urinary neopterin and toxicity of
      therapy in 12 patients with head and neck carcinoma during external-beam
      radiation. Urinary neopterin was determined daily by high-performance liquid
      chromatography. RESULTS: In addition to a trend for increased neopterin
      concentrations during radiation therapy, a significant association between
      changes of neopterin and toxicity and vice versa was observed with a rise of
      neopterin predicting a later manifestation of toxicity as well as manifestion of
      toxicity predicting a later rise of neopterin. CONCLUSION: Urinary neopterin is
      predictive of toxicity in patients with head and neck carcinoma. An association
      between toxicity and subsequent rise of urinary neopterin concentrations was also
      observed.

PMID- 24023356
TI  - Aberrant expression of CXCR4 and beta-catenin in pancreatic cancer.
AB  - AIM: The stromal cell-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4
      (CXCR4) axis and Wingless and INT-1 (Wnt)/beta-catenin pathway has been related
      to cancer progression. The aim of this study was to investigate the expression of
      CXCR4 and beta-catenin in pancreatic cancer. PATIENTS AND METHODS: A total of 48
      pancreatic cancer samples and 8 normal pancreatic tissues were selected to detect
      CXCR4 and beta-catenin expression by an immunohistological technique. Spearman
      and Chi-square analyses were used to study the relation between the protein
      expression and clinical characteristics. Survival analysis was evaluated by the
      Kaplan-Meier product limit method. RESULTS: The proportions of CXCR4 and beta
      catenin expression on pancreatic cancer cells were significantly higher than in
      normal pancreas tissues. There was a significant difference in CXRC4 expression
      levels, lymph node metastasis and TNM stage. Clinical Significance was observed
      for beta-catenin expression and lymph node metastasis; Kaplan-Meier curves
      suggested that clinical prognosis is poor for patients expressing CXCR4.
      Multivariate analysis showed that CXCR4 expression was an independent prognostic
      factor for pancreatic cancer. CONCLUSION: Both CXCR4 and beta-catenin are
      abnormally expressed in pancreatic cancer. CXCR4 may be an important marker for
      pancreatic cancer progression.

PMID- 24023357
TI  - Anal carcinoma: surgery does not influence prognosis when performed prior to
      concurrent radiochemotherapy.
AB  - BACKGROUND: Concurrent radiochemotherapy (cRCT) is the standard-of-care for
      patients with locally advanced anal cancer. There is a subgroup of patients
      however, vastly with small tumors, which undergo local excision before combined
      modality treatment. It was suggested that local excision prior to cRCT might
      improve the local control in comparison with cRCT. We evaluated local excision in
      comparison to incisional biopsy in this setting. PATIENTS AND METHODS: Between
      2000 and 2005, 84 patients were included in the study. In the majority of
      patients, only incisional biopsy (INC) was performed for the histopathological
      verification. Other patients underwent surgery prior to the RCT course as
      excisional biopsy (EXC). The chemotherapy consisted of 5-fluorouracil (800/1000
      mg/m(2)/d, 4 consecutive days, w 1, five) and mitomycin C (2 times 10 mg/m(2)).
      Radiotherapy was prescribed 45 at Gy. RESULTS: All patients (T1-2) were available
      for analysis. 14% of patients had node-positive disease. For the entire series,
      at five years and eight years, the actuarial OAS rates were 71% and 54%,
      respectively; the DSS rates were 74% and 68%, respectively; and the DFS rates
      were 54% and 54%, respectively. The actuarial control rate achieved by the EXC
      group was 80% after five years, better than the one for the INC group at 64%.
      Univariate analysis showed that tumor stage T3-T4 (p=0.04), tumor size >=6 cm
      (p<0.001), nodal stage N1-3 (p<0.00) and OTT >40 days (p=0.05) are significantly
      correlated with poorer local disease control. Local excision in comparison with
      INC did not prove to be significant for local disease control (p=0.45). No
      significance was found for pre-therapeutic prognostic factors age, gender,
      histological type and grading. Multivariate analysis showed that tumor size as
      continuous variable (p=0.02) and OTT (p=0.04) remained significant when adjusted
      for T-stage and nodal stage. CONCLUSION: According to this highly qualitative
      trial, surgical excision prior to cRCT, did not improve results. cRCT was
      confirmed as the standard-of-care.

PMID- 24023358
TI  - Image-guided radiotherapy with implanted markers and kilovoltage imaging and 6
      dimensional position corrections for intrafractional motion of the prostate.
AB  - BACKGROUND/AIM: To assess intrafractional prostate and patient movement using
      intra-prostatic fiducials and stereoscopic kilovoltage (kV) X-ray imaging in a 6
      dimensional (6D) position correction protocol. To evaluate potential gains of
      intra-treatment repositioning with respect to treatment margins. PATIENTS AND
      METHODS: In intensity-modulated radiotherapy of prostate cancer patients were
      positioned according to internal fiducials in six dimensions by the use of
      ExacTrac/Novalis BodyTM (ET/NB) System and a robotic couch. Intrafractional
      displacement of both, prostate and patient were analyzed in 427 treatment
      fractions of 13 patients. Systematic and random components were specified and
      used for intra-treatment margin calculation. The potential reduction of treatment
      margins, and intrafractional repositioning by use of the ET Snap Verification
      presumed, was simulated. RESULTS: The mean treatment duration was 14.2+/-2.6 min.
      Standard deviations (SDs) of the effective intrafractional target displacement in
      superior-inferior (SI) and anterior-posterior (AP) axes were 2.4 mm and 2.1 mm,
      respectively. Systematic errors for patient were 1.8 and 1.7 mm, and for prostate
      movement were 2.1 and 2.0 mm in SI and AP, respectively. The SDs of
      intrafractional rotation errors of the prostate around SI and left right (LR)
      were on average 2.2 and 3.6 degrees, respectively. Margins covering
      intrafractional motion were 4.5 and 4.3 mm in SI and AP without intrafractional
      correction and were estimated to 2.9 mm and 2.8 mm in SI and AP, respectively for
      simulated intra-treatment intervention. CONCLUSION: After positioning according
      to fiducials, intrafractional motion is significant for treatment margins.
      Despite correcting rotational deviations by couch angulation, the systematic
      error for the component of prostate motion was somewhat larger than that of
      patient displacement. Intrafractional correction could be useful in reducing
      treatment margins.

PMID- 24023359
TI  - Prognostic factors of metastatic or recurrent esophageal squamous cell carcinoma
      in patients receiving three-drug combination chemotherapy.
AB  - BACKGROUND: Three-drug combination therapy based on cisplatin/fluorouracil might
      improve treatment efficacy for metastatic esophageal squamous cell carcinoma
      (ESCC), but at the risk of increasing toxicity. The study sought to identify
      factors associated with outcomes of metastatic ESCC in patients who were treated
      with three-drug combinations. PATIENTS AND METHODS: One-hundred and thirteen
      patients with metastatic or recurrent ESCC who were treated with
      cisplatin/fluorouracil-based three-drug combination during 2000-2009 were
      studied. The prognostic impact of clinicopathological characteristics were
      evaluated by Cox proportional hazard regression analyses. RESULTS: The third
      chemotherapeutic agents comprised of paclitaxel, docetaxel, and methotrexate in
      76 (67%), 13 (12%), and 24 (21%) of patients, respectively. The overall response
      rate was 41%. The median overall survival (OS) was 8.5 months. Results of the Cox
      proportional hazard regression models showed that age >=65 years, Eastern
      Cooperative Oncology Group performance status of 0 and 1, lymph node-only
      metastasis and baseline white blood cell (WBC) count <=10,000/mm(3) were
      significant prognostic factors for better OS. The OS curves were significantly
      separated by risk groups comprising of age, metastasis status and WBC count as
      risk factors. CONCLUSION: The identification of prognostic factors could
      facilitate for future design of randomized studies on the efficacy of three-drug
      combinations for metastatic ESCC.

PMID- 24023360
TI  - Predictive factors for recurrence and survival in hepatocellular carcinoma in
      South Korea.
AB  - AIM: To evaluate the factors predicting for recurrence and to analyze survival of
      patients with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of
      743 patients who were consecutively diagnosed and treated with HCC were
      retrospectively analyzed from January 2004 to December 2012 at our institution.
      We analyzed their survival and tumor recurrence. RESULTS: On multivariate
      analysis, age >50 years, CLIP score <3, ALP <120 U/l, LDH <450 IU/l, CRP <0.8
      mg/dl, tumor size <6 cm, no distant metastasis, and curative treatment modality
      were predictors for 1-year survival. CRP <0.8 mg/dl, Child-Pugh score <7,
      curative treatment modality and tumor size <6 cm were predictors for 3-year
      survival. Absence of vascular invasion and uninodular tumor type were predictors
      for 5-year survival. Multinodular tumor, tumor size >4 cm, and palliative
      treatment were independent risk factors for 1-year recurrence after initial
      treatment. CONCLUSION: This large study provides a comprehensive overview of the
      survival outcomes and prognostic factors regarding HCC, according to clinical
      characteristics, various treatment modalities, and the results will help in the
      selection of effective treatment strategies future.

PMID- 24023364
TI  - Does parental response to children's pain moderate the association between pain
      severity and functional disability? An examination of noncardiac chest pain.
AB  - OBJECTIVE: We sought to examine whether parental responses to children's
      noncardiac chest pain moderate the relationship between child's pain severity and
      functional disability. METHODS: 77 children (ages 8-18 years) with noncardiac
      chest pain and their parents were recruited from pediatric cardiology clinics in
      Israel. Children completed measures assessing pain (intensity/frequency) and
      functioning. Parents and children completed measures assessing parental responses
      to children's pain. RESULTS: Parental protective responses (parent and child
      report) moderated the relationship between child's pain intensity and frequency
      and functional disability. Parental encouraging/monitoring responses (child
      report only) moderated the relationship between child's pain intensity and
      functional disability. As expected, the association between pain and disability
      was greater for children and adolescents whose parents were higher in these
      behaviors. CONCLUSIONS: Parental protective and encouraging/monitoring behavior
      may exacerbate the impact of pain on functioning. Interventions that promote more
      adaptive responses to children's pain may help reduce disability in youth with
      pain.

PMID- 24023365
TI  - An incidental finding of striking muscular hypertrophy leading to a diagnosis of
      Berardinelli Seip Congenital Lipodystrophy.

PMID- 24023366
TI  - A comparative evaluation on prediction methods of nucleosome positioning.
AB  - Nucleosome positioning plays an essential role in cellular processes by
      modulating accessibility of DNA to proteins. Many computational models have been
      developed to predict genome-wide nucleosome positions from DNA sequences.
      Comparative analysis of predicted and experimental nucleosome positioning maps
      facilitates understanding the regulatory mechanisms of transcription and DNA
      replication. Therefore, a comprehensive evaluation of existing computational
      methods is important and useful for biologists to choose appropriate ones in
      their research. In this article, we carried out a performance comparison among
      eight widely used computational methods on four species including yeast,
      fruitfly, mouse and human. In particular, we compared these methods on different
      regions of each species such as gene sequences, promoters and 5'UTR exons. The
      experimental results show that the performances of the two latest versions of the
      thermodynamic model are relatively steadier than the other four methods.
      Moreover, these methods are workable on four species, but their performances
      decrease gradually from yeast to human, indicating that the fundamental mechanism
      of nucleosome positioning is conserved through the evolution process, but more
      and more factors participate in the determination of nucleosome positions, which
      leads to sophisticated regulation mechanisms. 

PMID- 24023367
TI  - Hepatic basolateral efflux contributes significantly to rosuvastatin disposition
      I: characterization of basolateral versus biliary clearance using a novel
      protocol in sandwich-cultured hepatocytes.
AB  - Transporters responsible for hepatic uptake and biliary clearance (CLBile) of
      rosuvastatin (RSV) have been well characterized. However, the contribution of
      basolateral efflux clearance (CLBL) to hepatic and systemic exposure of RSV is
      unknown. Additionally, the appropriate design of in vitro hepatocyte efflux
      experiments to estimate CLBile versus CLBL remains to be established. A novel
      uptake and efflux protocol was developed in sandwich-cultured hepatocytes (SCH)
      to achieve desired tight junction modulation while maintaining cell viability.
      Subsequently, studies were conducted to determine the role of CLBL in the hepatic
      disposition of RSV using SCH from wild-type (WT) and multidrug resistance
      associated protein 2 (Mrp2)-deficient (TR(-)) rats in the absence and presence of
      the P-glycoprotein and breast cancer resistance protein (Bcrp) inhibitor
      elacridar (GF120918). RSV CLBile was nearly ablated by GF120918 in TR(-) SCH,
      confirming that Mrp2 and Bcrp are responsible for the majority of RSV CLBile.
      Pharmacokinetic modeling revealed that CLBL and CLBile represent alternative
      elimination routes with quantitatively similar contributions to the overall
      hepatocellular excretion of RSV in rat SCH under baseline conditions (WT SCH in
      the absence of GF120918) and also in human SCH. Membrane vesicle experiments
      revealed that RSV is a substrate of MRP4 (Km = 21 +/- 7 uM, Vmax = 1140 +/- 210
      pmol/min per milligram of protein). Alterations in MRP4-mediated RSV CLBL due to
      drug-drug interactions, genetic polymorphisms, or disease states may lead to
      changes in hepatic and systemic exposure of RSV, with implications for the safety
      and efficacy of this commonly used medication. 

PMID- 24023369
TI  - Sixteen-year change in acoustic-admittance measures among older adults: data from
      a population-based study.
AB  - PURPOSE: The primary purpose of this study was to measure the 16-year change in
      peak compensated static acoustic admittance (Peak Y(tm)) in a population-based
      cohort of older adults, and to determine whether age was associated with any
      observed change in Peak Y(tm). Other tympanometric measures also were taken and
      analyzed. METHOD: Data from two examinations (1993-1995 and 2009-2010) of the
      population-based Epidemiology of Hearing Loss Study (n = 1,439 with data at both
      examinations, ages 48-84 years at baseline) were utilized to assess 16-year
      change. Tympanometric measures were taken using a 226-Hz probe tone, a positive
      to-negative direction of pressure change, and a measured pump speed of 600/200
      daPa/s. RESULTS: During the 16-year period, Peak Y(tm) declined an average of
      0.009 mmho/year (0.009/year for women, 0.007/year for men). Among women, older
      baseline age was associated with greater decline in Peak Y(tm). Among men,
      baseline age was associated with change in Peak Y(tm), but in a nonlinear
      pattern. Other tympanometric measures demonstrated little change after 16 years.
      CONCLUSIONS: These results demonstrate a small degree of middle-ear stiffening
      after 16 years among these older adults, but not enough to affect function in a
      manner that would influence clinical decisions.

PMID- 24023368
TI  - Pharmacological inhibition of pleckstrin homology domain leucine-rich repeat
      protein phosphatase is neuroprotective: differential effects on astrocytes.
AB  - Pleckstrin homology domain and leucine-rich repeat protein phosphatase 1 (PHLPP1)
      inhibits protein kinase B (AKT) survival signaling in neurons. Small molecule pan
      PHLPP inhibitors (selective for PHLPP1 and PHLPP2) may offer a translatable
      method to induce AKT neuroprotection. We tested several recently discovered PHLPP
      inhibitors (NSC117079 and NSC45586; benzoic acid, 5-[2-[4-[2-(2,4-diamino-5
      methylphenyl)diazenyl]phenyl]diazenyl]-2-hydroxy-,sodium salt.) in rat cortical
      neurons and astrocytes and compared the biochemical response of these agents with
      short hairpin RNA (shRNA)-mediated PHLPP1 knockdown (KD). In neurons, both PHLPP1
      KD and experimental PHLPP inhibitors activated AKT and ameliorated staurosporine
      (STS)-induced cell death. Unexpectedly, in astrocytes, both inhibitors blocked
      AKT activation, and NSC117079 reduced viability. Only PHLPP2 KD mimicked PHLPP
      inhibitors on astrocyte biochemistry. This suggests that these inhibitors could
      have possible detrimental effects on astrocytes by blocking novel PHLPP2-mediated
      prosurvival signaling mechanisms. Finally, because PHLPP1 levels are reportedly
      high in the hippocampus (a region prone to ischemic death), we characterized
      hippocampal changes in PHLPP and several AKT targeting prodeath phosphatases
      after cardiac arrest (CA)-induced brain injury. PHLPP1 levels increased in rat
      brains subjected to CA. None of the other AKT inhibitory phosphatases increased
      after global ischemia (i.e., PHLPP2, PTEN, PP2A, and PP1). Selective PHLPP1
      inhibition (such as by shRNA KD) activates AKT survival signaling in neurons and
      astrocytes. Nonspecific PHLPP inhibition (by NSC117079 and NSC45586) only
      activates AKT in neurons. Taken together, these results suggest that selective
      PHLPP1 inhibitors should be developed and may yield optimal strategies to protect
      injured hippocampal neurons and astrocytes-namely from global brain ischemia. 

PMID- 24023370
TI  - Effect of sustained maternal responsivity on later vocabulary development in
      children with fragile X syndrome.
AB  - PURPOSE: This research explored whether sustained maternal responsivity (a parent
      child interaction style characterized by warmth, nurturance, and stability as
      well as specific behaviors, such as contingent positive responses to child
      initiations) was a significant variable predicting vocabulary development of
      children with fragile X syndrome through age 9 years. METHOD: Fifty-five mother
      child dyads were followed longitudinally when children were between 2 and 10
      years of age. Measures of maternal responsivity and child vocabulary were
      obtained at regular intervals starting at age 2.9 years. Sustained responsivity
      was indicated by the average responsivity measured over Observations 2-5.
      Responsivity at the 1st time period, autism symptoms, and cognitive development
      were used as control variables. RESULTS: After controlling for development and
      autism symptoms, the authors found significant effects for sustained responsivity
      on receptive vocabulary, expressive vocabulary, and the rate of different words
      children produced through age 9. CONCLUSIONS: Maternal responsivity, which is
      typically a variable of interest during early childhood, continues to be a
      significant variable, predicting vocabulary development through the middle
      childhood period. Thus, responsivity is a potential target for language
      interventions through this age period.

PMID- 24023371
TI  - Cognitive and linguistic sources of variance in 2-year-olds' speech-sound
      discrimination: a preliminary investigation.
AB  - PURPOSE: This preliminary investigation explored potential cognitive and
      linguistic sources of variance in 2-year-olds' speech-sound discrimination by
      using the toddler change/ no-change procedure and examined whether modifications
      would result in a procedure that can be used consistently with younger 2-year
      olds. METHOD: Twenty typically developing 2-year-olds completed the newly
      modified toddler change/no-change procedure. Behavioral tests and parent report
      questionnaires were used to measure several cognitive and linguistic constructs.
      Stepwise linear regression was used to relate discrimination sensitivity to the
      cognitive and linguistic measures. In addition, discrimination results from the
      current experiment were compared with those from 2-year-old children tested in a
      previous experiment. RESULTS: Receptive vocabulary and working memory explained
      56.6% of variance in discrimination performance. Performance was not different on
      the modified toddler change/no-change procedure used in the current experiment
      from in a previous investigation, which used the original version of the
      procedure. CONCLUSIONS: The relationship between speech discrimination and
      receptive vocabulary and working memory provides further evidence that the
      procedure is sensitive to the strength of perceptual representations. The role
      for working memory might also suggest that there are specific subject-related,
      nonsensory factors limiting the applicability of the procedure to children who
      have not reached the necessary levels of cognitive and linguistic development.

PMID- 24023372
TI  - Interaction of language processing and motor skill in children with specific
      language impairment.
AB  - PURPOSE: To examine how language production interacts with speech motor and gross
      and fine motor skill in children with specific language impairment (SLI). METHOD:
      Eleven children with SLI and 12 age-matched peers (4-6 years) produced
      structurally primed sentences containing particles and prepositions. Utterances
      were analyzed for errors and for articulatory duration and variability. Standard
      measures of motor, language, and articulation skill were also obtained. RESULTS:
      Sentences containing particles, as compared with prepositions, were less likely
      to be produced in a priming task and were longer in duration, suggesting
      increased difficulty with this syntactic structure. Children with SLI
      demonstrated higher articulatory variability and poorer gross and fine motor
      skills compared with aged-matched controls. Articulatory variability was
      correlated with generalized gross and fine motor performance. CONCLUSIONS:
      Children with SLI show co-occurring speech motor and generalized motor deficits.
      Current theories do not fully account for the present findings, though the
      procedural deficit hypothesis provides a framework for interpreting overlap among
      language and motor domains.

PMID- 24023373
TI  - Age differences in speech motor performance on a novel speech task.
AB  - PURPOSE: The study was aimed at characterizing age-related changes in speech
      motor performance on a nonword repetition task as a function of practice and
      nonword length and complexity. METHOD: Nonword repetition accuracy, lip aperture
      coordination, and nonword production durations were assessed on 2 consecutive
      days for 16 young and 16 elderly participants for the production of 6 novel
      nonwords increasing in length and complexity. RESULTS: The effect of age on the
      ability to accurately and rapidly repeat long, complex nonwords was significant.
      However, the authors found no differences between the speech motor coordinative
      patterns of young and elderly adults. Further, the authors demonstrated age- and
      nonword-specific within- and between-session gains in speech motor performance.
      CONCLUSIONS: The authors speculate that cognitive, sensory, and motor factors
      interact in complex ways in elderly individuals to produce individual differences
      in nonword repetition ability at the levels of both behavioral and speech motor
      performance.

PMID- 24023374
TI  - Preterm and term infants' perception of temporally coordinated syllable-object
      pairings: implications for lexical development.
AB  - PURPOSE: This experimental study examined term infants (n = 34) and low-risk near
      term preterm infants (gestational age 32-36 weeks) at 2 months chronological age
      (n = 34) and corrected age (n =16). The study investigated whether the preterm
      infants presented with a delay in their sensitivity to synchronous syllable
      object pairings when compared with term infants. METHOD: First, infants were
      habituated to a single syllable, [tah] or [gah], spoken in synchrony with the
      motions of 1 of 4 toy objects, a crab, a porcupine, a star, or a lamb chop. Next,
      the infants received 2 syllable- and 2 object-change test trials, counterbalanced
      for order. RESULTS: After factoring out differential looking time during
      habituation, the study found that preterm infants showed attenuated looks to the
      change in the object and the change in the syllable relative to term infants.
      CONCLUSIONS: These findings suggest that even near-term preterm infants present
      with a delay in their sensitivity to synchrony in syllable-object pairings
      relative to term infants. Given the important role that synchrony plays in word
      mapping at 6-9 months, this early delay in sensitivity to synchrony might be an
      indicator of word mapping delays found in older preterm infants.

PMID- 24023376
TI  - Why words are hard for adults with developmental language impairments.
AB  - PURPOSE: To determine whether word learning problems associated with
      developmental language impairment (LI) reflect deficits in encoding or subsequent
      remembering of forms and meanings. METHOD: Sixty-nine 18- to 25-year-olds with LI
      or without (the normal development [ND] group) took tests to measure learning of
      16 word forms and meanings immediately after training (encoding) and 12 hr, 24
      hr, and 1 week later (remembering). Half of the participants trained in the
      morning, and half trained in the evening. RESULTS: At immediate posttest,
      participants with LI performed more poorly on form and meaning than those with
      ND. Poor performance was more likely among those with more severe LI. The LI-ND
      gap for word form recall widened over 1 week. In contrast, the LI and ND groups
      demonstrated no difference in remembering word meanings over the week. In both
      groups, participants who trained in the evening, and therefore slept shortly
      after training, demonstrated greater gains in meaning recall than those who
      trained in the morning. CONCLUSIONS: Some adults with LI have encoding deficits
      that limit the addition of word forms and meanings to the lexicon. Similarities
      and differences in patterns of remembering in the LI and ND groups motivate the
      hypothesis that consolidation of declarative memory is a strength for adults with
      LI.

PMID- 24023377
TI  - Tongue motion patterns in post-glossectomy and typical speakers: a principal
      components analysis.
AB  - PURPOSE: In this study, the authors examined changes in tongue motion caused by
      glossectomy surgery. A speech task that involved subtle changes in tongue-tip
      positioning (the motion from /i/ to /s/) was measured. The hypothesis was that
      patients would have limited motion on the tumor (resected) side and would
      compensate with greater motion on the nontumor side in order to elevate the
      tongue tip and blade for /s/. METHOD: Velocity fields were extracted from tagged
      magnetic resonance images in the left, middle, and right tongue of 3 patients and
      10 controls. Principal components (PCs) analysis quantified motion differences
      and distinguished between the subject groups. RESULTS: PCs 1 and 2 represented
      variance in (a) size and independence of the tongue tip, and (b) direction of
      motion of the tip, body, or both. Patients and controls were correctly separated
      by a small number of PCs. CONCLUSIONS: Motion of the tumor slice was different
      between patients and controls, but the nontumor side of the patients' tongues did
      not show excessive or adaptive motion. Both groups contained apical and laminal
      /s/ users, and 1 patient created apical /s/ in a highly unusual manner.

PMID- 24023378
TI  - Perception of speech modulation cues by 6-month-old infants.
AB  - PURPOSE: The capacity of 6-month-old infants to discriminate a voicing contrast
      (/aba/-/apa/) on the basis of amplitude modulation (AM) cues and frequency
      modulation (FM) cues was evaluated. METHOD: Several vocoded speech conditions
      were designed to either degrade FM cues in 4 or 32 bands or degrade AM in 32
      bands. Infants were familiarized to the vocoded stimuli for a period of either 1
      or 2 min. Vocoded speech discrimination was assessed using the head-turn
      preference procedure. RESULTS: Infants discriminated /aba/ from /apa/ in each
      condition; however, familiarization time was found to influence strongly infants'
      responses (i.e., their preference for novel vs. familiar stimuli). CONCLUSIONS:
      Six-month-old infants do not require FM cues and can use the slowest (< 16 Hz) AM
      cues to discriminate voicing. Moreover, 6-month-old infants can use AM cues
      extracted from only 4 broad-frequency bands to discriminate voicing.

PMID- 24023379
TI  - Auditory middle latency responses in chronic smokers compared to nonsmokers:
      differential effects of stimulus and age.
AB  - PURPOSE: Effects of clicks and tonebursts on early and late auditory middle
      latency response (AMLR) components were evaluated in young and older cigarette
      smokers and nonsmokers. METHOD: Participants ( n = 49) were categorized by
      smoking and age into 4 groups: (a) older smokers, (b) older nonsmokers, (c) young
      smokers, and (d) young nonsmokers. Monaural, 2-channel AMLRs were acquired from
      Fz and Cz electrodes with 3 stimuli (clicks, 500 Hz, and 3000 Hz). RESULTS: Group
      differences included significantly higher V-Na amplitude in young adults and
      shorter Pb latency in older nonsmokers. Young smokers had a significantly higher
      Nb-Pb amplitude and shorter Nb latency than other groups. Toneburst stimuli
      yielded significantly longer V, Na, and Pa latencies compared to clicks. Pb
      latency was shorter at Fz than at Cz. Relative amplitudes were significantly
      higher at Fz than at Cz overall; Pa-Nb and Nb-Pb were significantly lower for
      3000 Hz than for 500 Hz and clicks. CONCLUSIONS: Responses from young smokers
      revealed a higher amplitude and shorter latency for later AMLR waves, reflecting
      an arousal effect of smoking in cortical and subcortical generators. AMLR
      differences in older adults may be due to age-related neurochemical changes in
      the central nervous system. Stimulus and electrode differences plus smoking and
      aging effects can guide neurodiagnostic AMLR protocols, especially in young adult
      smokers.

PMID- 24023380
TI  - Effects of spaced retrieval training on semantic memory in Alzheimer's disease: a
      systematic review.
AB  - PURPOSE: This article reports on a systematic review and meta-analysis of the
      effects of spaced retrieval training (SRT) on semantic memory in people with
      Alzheimer's disease (AD) or related disorder. METHOD: An initial systematic
      database search identified 454 potential studies. After screening and de
      duplication, 35 studies that used SRT with the population of interest remained.
      The authors used an appraisal point system to evaluate the quality of the
      studies. Twelve of the 35 studies met inclusion and exclusion criteria and passed
      the appraisal point system cutoff. The 12 studies were classified as Level I and
      II evidence. RESULTS: Although the 12 studies varied in terms of design,
      methodology, and quality, SRT was shown to have important positive effects on
      learning semantic information across the included studies. CONCLUSIONS: The
      findings indicate that SRT is an effective semantic memory training technique for
      people with AD, and consequently, recommendations are suggested for implementing
      SRT in practice settings. Continued research in this domain is also warranted to
      address limitations and gaps in the current body of research evidence, including
      variability in SRT protocols, effects of dementia severity on learning outcomes,
      maintenance effects, generalization, and the role of explicit and implicit
      learning in SRT.

PMID- 24023381
TI  - Gender categorization in cochlear implant users.
AB  - PURPOSE: In this study, the authors examined the ability of subjects with
      cochlear implants (CIs) to discriminate voice gender and how this ability evolved
      as a function of CI experience. METHOD: The authors presented a continuum of
      voice samples created by voice morphing, with 9 intermediate acoustic parameter
      steps between a typical male and a typical female. This method allowed for the
      evaluation of gender categorization not only when acoustical features were
      specific to gender but also for more ambiguous cases, when fundamental frequency
      or formant distribution were located between typical values. RESULTS: Results
      showed a global, though variable, deficit for voice gender categorization in CI
      recipients compared with subjects with normal hearing. This deficit was stronger
      for ambiguous stimuli in the voice continuum: Average performance scores for CI
      users were 58% lower than average scores for subjects with normal hearing in
      cases of ambiguous stimuli and 19% lower for typical male and female voices. The
      authors found no significant improvement in voice gender categorization with CI
      experience. CONCLUSIONS: These results emphasize the dissociation between
      recovery of speech recognition and voice feature perception after cochlear
      implantation. This large and durable deficit may be related to spectral and
      temporal degradation induced by CI sound coding, or it may be related to central
      voice processing deficits.

PMID- 24023382
TI  - Total and conceptual vocabulary in Spanish-English bilinguals from 22 to 30
      months: implications for assessment.
AB  - PURPOSE: Vocabulary assessment holds promise as a way to identify young bilingual
      children at risk for language delay. This study compares 2 measures of vocabulary
      in a group of young Spanish-English bilingual children to a single-language
      measure used with monolingual children. METHOD: Total vocabulary and conceptual
      vocabulary were used to measure mean vocabulary size and growth in 47 Spanish
      English bilingually developing children from 22 to 30 months of age based on
      results from the MacArthur-Bates Communicative Development Inventory (CDI; Fenson
      et al., 1993) and the Inventario del Desarrollo de Habilidades Comunicativas (
      Jackson-Maldonado et al., 2003). Bilingual children's scores of total vocabulary
      and conceptual vocabulary were compared with CDI scores for a control group of 56
      monolingual children. RESULTS: The total vocabulary measure resulted in mean
      vocabulary scores and average rate of growth similar to monolingual growth,
      whereas conceptual vocabulary scores were significantly smaller and grew at a
      slower rate than total vocabulary scores. Total vocabulary identified the same
      proportion of bilingual children below the 25th percentile on monolingual norms
      as the CDI did for monolingual children. CONCLUSION: These results support the
      use of total vocabulary as a means of assessing early language development in
      young bilingual Spanish-English speaking children.

PMID- 24023383
TI  - Effects of lexical tone contour on Mandarin sentence intelligibility.
AB  - PURPOSE: This study examined the effects of lexical tone contour on the
      intelligibility of Mandarin sentences in quiet and in noise. METHOD: A text-to
      speech synthesis engine was used to synthesize Mandarin sentences with each word
      carrying the original lexical tone, flat tone, or a tone randomly selected from
      the 4 Mandarin lexical tones. The synthesized speech signals were presented to 11
      normal-hearing listeners for recognition in quiet and in speech-shaped noise at 0
      dB signal-to-noise ratio. RESULTS: Normal-hearing listeners nearly perfectly
      recognized the Mandarin sentences produced with modified tone contours in quiet;
      however, performance declined substantially in noise. CONCLUSIONS: Consistent
      with previous findings to some extent, the present findings suggest that lexical
      tones are relatively redundant cues for Mandarin sentence intelligibility in
      quiet and that other cues could compensate for the distorted lexical tone
      contour. However, in noise, the results provide direct evidence that lexical tone
      contour is important for the recognition of Mandarin sentences.

PMID- 24023384
TI  - Escherichia coli biofilms have an organized and complex extracellular matrix
      structure.
AB  - Bacterial biofilms are ubiquitous in nature, and their resilience is derived in
      part from a complex extracellular matrix that can be tailored to meet
      environmental demands. Although common developmental stages leading to biofilm
      formation have been described, how the extracellular components are organized to
      allow three-dimensional biofilm development is not well understood. Here we show
      that uropathogenic Escherichia coli (UPEC) strains produce a biofilm with a
      highly ordered and complex extracellular matrix (ECM). We used electron
      microscopy (EM) techniques to image floating biofilms (pellicles) formed by UPEC.
      EM revealed intricately constructed substructures within the ECM that encase
      individual, spatially segregated bacteria with a distinctive morphology.
      Mutational and biochemical analyses of these biofilms confirmed curli as a major
      matrix component and revealed important roles for cellulose, flagella, and type 1
      pili in pellicle integrity and ECM infrastructure. Collectively, the findings of
      this study elucidated that UPEC pellicles have a highly organized ultrastructure
      that varies spatially across the multicellular community. IMPORTANCE: Bacteria
      can form biofilms in diverse niches, including abiotic surfaces, living cells,
      and at the air-liquid interface of liquid media. Encasing these cellular
      communities is a self-produced extracellular matrix (ECM) that can be composed of
      proteins, polysaccharides, and nucleic acids. The ECM protects biofilm bacteria
      from environmental insults and also makes the dissolution of biofilms very
      challenging. As a result, formation of biofilms within humans (during infection)
      or on industrial material (such as water pipes) has detrimental and costly
      effects. In order to combat bacterial biofilms, a better understanding of
      components required for biofilm formation and the ECM is required. This study
      defined the ECM composition and architecture of floating pellicle biofilms formed
      by Escherichia coli.

PMID- 24023385
TI  - Engineering a replication-competent, propagation-defective Middle East
      respiratory syndrome coronavirus as a vaccine candidate.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging
      coronavirus infecting humans that is associated with acute pneumonia, occasional
      renal failure, and a high mortality rate and is considered a threat to public
      health. The construction of a full-length infectious cDNA clone of the MERS-CoV
      genome in a bacterial artificial chromosome is reported here, providing a reverse
      genetics system to study the molecular biology of the virus and to develop
      attenuated viruses as vaccine candidates. Following transfection with the cDNA
      clone, infectious virus was rescued in both Vero A66 and Huh-7 cells. Recombinant
      MERS-CoVs (rMERS-CoVs) lacking the accessory genes 3, 4a, 4b, and 5 were
      successfully rescued from cDNA clones with these genes deleted. The mutant
      viruses presented growth kinetics similar to those of the wild-type virus,
      indicating that accessory genes were not essential for MERS-CoV replication in
      cell cultures. In contrast, an engineered mutant virus lacking the structural E
      protein (rMERS-CoV-DeltaE) was not successfully rescued, since viral infectivity
      was lost at early passages. Interestingly, the rMERS-CoV-DeltaE genome replicated
      after cDNA clone was transfected into cells. The infectious virus was rescued and
      propagated in cells expressing the E protein in trans, indicating that this virus
      was replication competent and propagation defective. Therefore, the rMERS-CoV
      DeltaE mutant virus is potentially a safe and promising vaccine candidate to
      prevent MERS-CoV infection. IMPORTANCE: Since the emergence of MERS-CoV in the
      Arabian Peninsula during the summer of 2012, it has already spread to 10
      different countries, infecting around 94 persons and showing a mortality rate
      higher than 50%. This article describes the development of the first reverse
      genetics system for MERS-CoV, based on the construction of an infectious cDNA
      clone inserted into a bacterial artificial chromosome. Using this system, a
      collection of rMERS-CoV deletion mutants has been generated. Interestingly, one
      of the mutants with the E gene deleted was a replication-competent, propagation
      defective virus that could only be grown in the laboratory by providing E protein
      in trans, whereas it would only survive a single virus infection cycle in vivo.
      This virus constitutes a vaccine candidate that may represent a balance between
      safety and efficacy for the induction of mucosal immunity, which is needed to
      prevent MERS-CoV infection.

PMID- 24023387
TI  - Deciphering the origins and tracking the evolution of cholera epidemics with
      whole-genome-based molecular epidemiology.
AB  - The devastating Haitian cholera outbreak that began in October 2010 is the first
      known cholera epidemic in this island nation. Epidemiological and genomic data
      have provided strong evidence that United Nations security forces from Nepal
      introduced toxigenic Vibrio cholerae O1, the cause of epidemic cholera, to Haiti
      shortly before the outbreak arose. However, some have contended that indigenous
      V. cholerae contributed to the outbreak. In a recent paper (mBio 4:e00398-13,
      2013), L. S. Katz et al. explored the nature and rate of changes in this ancient
      pathogen's genome during an outbreak, based on whole-genome sequencing of 23
      Haitian V. cholerae clinical isolates obtained over a 20-month period. Notably,
      they detected point mutations, deletions, and inversions but found no insertion
      of horizontally transmitted DNA, arguing strongly against the idea that
      autochthonous V. cholerae donated DNA to the outbreak strain. Furthermore, they
      found that Haitian epidemic V. cholerae isolates were virtually untransformable.
      Comparative genomic analyses revealed that the Haitian isolates were nearly
      identical to isolates from Nepal and that the Nepalese-Haitian isolates were
      distinguishable from isolates circulating elsewhere in the world. Reconstruction
      of the phylogeny of the Haitian isolates was consistent with a single
      introduction of V. cholerae to Haiti sometime between late July and late October
      2010, dates remarkably concordant with epidemiological observations. In
      aggregate, this paper provides additional compelling evidence that the V.
      cholerae strain responsible for the Haitian cholera epidemic came from Nepal and
      illustrates the power of whole-genome-based analyses for epidemiology, pathogen
      evolution, and forensics.

PMID- 24023386
TI  - Novel role for the Streptococcus pneumoniae toxin pneumolysin in the assembly of
      biofilms.
AB  - Streptococcus pneumoniae is an important commensal and pathogen responsible for
      almost a million deaths annually in children under five. The formation of
      biofilms by S. pneumoniae is important in nasopharyngeal colonization, pneumonia,
      and otitis media. Pneumolysin (Ply) is a toxin that contributes significantly to
      the virulence of S. pneumoniae and is an important candidate as a serotype
      independent vaccine target. Having previously demonstrated that a luxS knockout
      mutant was unable to form early biofilms and expressed less ply mRNA than the
      wild type, we conducted a study to investigate the role of Ply in biofilm
      formation. We found that Ply was expressed in early phases of biofilm development
      and localized to cellular aggregates as early as 4 h postinoculation. S.
      pneumoniae ply knockout mutants in D39 and TIGR4 backgrounds produced
      significantly less biofilm biomass than wild-type strains at early time points,
      both on polystyrene and on human respiratory epithelial cells, cultured under
      static or continuous-flow conditions. Ply's role in biofilm formation appears to
      be independent of its hemolytic activity, as S. pneumoniae serotype 1 strains,
      which produce a nonhemolytic variant of Ply, were still able to form biofilms.
      Transmission electron microscopy of biofilms grown on A549 lung cells using
      immunogold demonstrated that Ply was located both on the surfaces of pneumococcal
      cells and in the extracellular biofilm matrix. Altogether, our studies
      demonstrate a novel role for pneumolysin in the assembly of S. pneumoniae
      biofilms that is likely important during both carriage and disease and therefore
      significant for pneumolysin-targeting vaccines under development. IMPORTANCE: The
      bacterium Streptococcus pneumoniae (commonly known as the pneumococcus) is
      commonly carried in the human nasopharynx and can spread to other body sites to
      cause disease. In the nasopharynx, middle ear, and lungs, the pneumococcus forms
      multicellular surface-associated structures called biofilms. Pneumolysin is an
      important toxin produced by almost all S. pneumoniae strains, extensively studied
      for its ability to cause damage to human tissue. In this paper, we demonstrate
      that pneumolysin has a previously unrecognized role in biofilm formation by
      showing that strains without pneumolysin are unable to form the same amount of
      biofilm on plastic and human cell substrates. Furthermore, we show that the role
      of pneumolysin in biofilm formation is separate from the hemolytic activity
      responsible for tissue damage during pneumococcal diseases. This novel role for
      pneumolysin suggests that pneumococcal vaccines directed against this protein
      should be investigated for their potential impact on biofilms formed during
      carriage and disease.

PMID- 24023388
TI  - Proton-dependent gating and proton uptake by Wzx support O-antigen-subunit
      antiport across the bacterial inner membrane.
AB  - Wzx flippases are crucial for bacterial cell surface polysaccharide assembly as
      they transport undecaprenyl pyrophosphate-linked sugar repeat units from the
      cytoplasmic to the periplasmic leaflets of the inner membrane (IM) for final
      assembly. Our recently reported three-dimensional (3D) model structure of Wzx
      from Pseudomonas aeruginosa PAO1 (WzxPa) displayed a cationic internal vestibule
      and functionally essential acidic amino acids within transmembrane segment
      bundles. Herein, we examined the intrinsic transport function of WzxPa following
      its purification and reconstitution in phospholipid liposomes. WzxPa was capable
      of mediating anion flux, consistent with its cationic interior. This flux was
      electrogenic and modified by extraliposomal pH. Mutation of the above-mentioned
      acidic residues (E61, D269, and D359) reduced proton (H(+))-modified anion flux,
      showing the role of these amino acid side chains in H(+)-dependent transport. Wzx
      also mediated acidification of the proteoliposome interior in the presence of an
      outward anion gradient. These results indicate H(+)-dependent gating and H(+)
      uptake by WzxPa and allow for the first H(+)-dependent antiport mechanism to be
      proposed for lipid-linked oligosaccharide translocation across the bacterial IM.
      IMPORTANCE Many bacterial cell surface polysaccharides that are important for
      survival and virulence are synthesized at the periplasmic leaflet of the inner
      membrane (IM) using precursors produced in the cytoplasm. Wzx flippases are
      responsible for translocation of lipid-linked sugar repeat units across the IM
      and had been previously suggested to simply facilitate passive substrate
      diffusion. Through our characterization of purified Wzx in a reconstitution
      system described herein, we have observed protein-dependent intrinsic transport
      producing a change in the electrical potential of the system, with H(+)
      identified as the coupling ion. These results provide the first evidence for
      coupled (i.e., secondary active) transport by these proteins and, in conjunction
      with structural data, allow for an antiport mechanism to be proposed for the
      directed transport of lipid-linked sugar substrates across the IM. These findings
      bring our understanding of lipid-linked polysaccharide transporter proteins more
      in line with the efflux pumps to which they are evolutionarily related.

PMID- 24023390
TI  - Large-scale top-down proteomics of the human proteome: membrane proteins,
      mitochondria, and senescence.
AB  - Top-down proteomics is emerging as a viable method for the routine identification
      of hundreds to thousands of proteins. In this work we report the largest top-down
      study to date, with the identification of 1,220 proteins from the transformed
      human cell line H1299 at a false discovery rate of 1%. Multiple separation
      strategies were utilized, including the focused isolation of mitochondria,
      resulting in significantly improved proteome coverage relative to previous work.
      In all, 347 mitochondrial proteins were identified, including ~50% of the
      mitochondrial proteome below 30 kDa and over 75% of the subunits constituting the
      large complexes of oxidative phosphorylation. Three hundred of the identified
      proteins were found to be integral membrane proteins containing between 1 and 12
      transmembrane helices, requiring no specific enrichment or modified LC-MS
      parameters. Over 5,000 proteoforms were observed, many harboring post
      translational modifications, including over a dozen proteins containing lipid
      anchors (some previously unknown) and many others with phosphorylation and
      methylation modifications. Comparison between untreated and senescent H1299 cells
      revealed several changes to the proteome, including the hyperphosphorylation of
      HMGA2. This work illustrates the burgeoning ability of top-down proteomics to
      characterize large numbers of intact proteoforms in a high-throughput fashion.

PMID- 24023389
TI  - Vascular endothelial growth factor (VEGF) and platelet (PF-4) factor 4 inputs
      modulate human microvascular endothelial signaling in a three-dimensional matrix
      migration context.
AB  - The process of angiogenesis is under complex regulation in adult organisms,
      particularly as it often occurs in an inflammatory post-wound environment. As
      such, there are many impacting factors that will regulate the generation of new
      blood vessels which include not only pro-angiogenic growth factors such as
      vascular endothelial growth factor, but also angiostatic factors. During initial
      postwound hemostasis, a large initial bolus of platelet factor 4 is released into
      localized areas of damage before progression of wound healing toward tissue
      homeostasis. Because of its early presence and high concentration, the
      angiostatic chemokine platelet factor 4, which can induce endothelial anoikis,
      can strongly affect angiogenesis. In our work, we explored signaling crosstalk
      interactions between vascular endothelial growth factor and platelet factor 4
      using phosphotyrosine-enriched mass spectrometry methods on human dermal
      microvascular endothelial cells cultured under conditions facilitating migratory
      sprouting into collagen gel matrices. We developed new methods to enable mass
      spectrometry-based phosphorylation analysis of primary cells cultured on collagen
      gels, and quantified signaling pathways over the first 48 h of treatment with
      vascular endothelial growth factor in the presence or absence of platelet factor
      4. By observing early and late signaling dynamics in tandem with correlation
      network modeling, we found that platelet factor 4 has significant crosstalk with
      vascular endothelial growth factor by modulating cell migration and polarization
      pathways, centered around P38alpha MAPK, Src family kinases Fyn and Lyn, along
      with FAK. Interestingly, we found EphA2 correlational topology to strongly
      involve key migration-related signaling nodes after introduction of platelet
      factor 4, indicating an influence of the angiostatic factor on this ambiguous but
      generally angiogenic signal in this complex environment. 

PMID- 24023391
TI  - The novel caspase-3 substrate Gap43 is involved in AMPA receptor endocytosis and
      long-term depression.
AB  - The cysteine protease caspase-3, best known as an executioner of cell death in
      apoptosis, also plays a non-apoptotic role in N-methyl-d-aspartate receptor
      dependent long-term depression of synaptic transmission (NMDAR-LTD) and alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor endocytosis in
      neurons. The mechanism by which caspase-3 regulates LTD and AMPA receptor
      endocytosis, however, remains unclear. Here, we addressed this question by using
      an enzymatic N-terminal peptide enrichment method and mass spectrometry to
      identify caspase-3 substrates in neurons. Of the many candidates revealed by this
      proteomic study, we have confirmed BASP1, Dbn1, and Gap43 as true caspase-3
      substrates. Moreover, in hippocampal neurons, Gap43 mutants deficient in caspase
      3 cleavage inhibit AMPA receptor endocytosis and LTD. We further demonstrated
      that Gap43, a protein well-known for its functions in axons, is also localized at
      postsynaptic sites. Our study has identified Gap43 as a key caspase-3 substrate
      involved in LTD and AMPA receptor endocytosis, uncovered a novel postsynaptic
      function for Gap43 and provided new insights into how long-term synaptic
      depression is induced. 

PMID- 24023393
TI  - A simple, tunable, and highly sensitive radio-frequency sensor.
AB  - We report a radio frequency (RF) sensor that exploits tunable attenuators and
      phase shifters to achieve high-sensitivity and broad band frequency tunability.
      Three frequency bands are combined to enable sensor operations from ~20 MHz to
      ~38 GHz. The effective quality factor (Qeff ) of the sensor is as high as ~3.8 *
      106 with 200 MUl of water samples. We also demonstrate the measurement of 2
      proponal-water-solution permittivity at 0.01 mole concentration level from ~1 GHz
      to ~10 GHz. Methanol-water solution and de-ionized water are used to calibrate
      the RF sensor for the quantitative measurements.

PMID- 24023392
TI  - Genes that escape X-inactivation in humans have high intraspecific variability in
      expression, are associated with mental impairment but are not slow evolving.
AB  - In female mammals most X-linked genes are subject to X-inactivation. However, in
      humans some X-linked genes escape silencing, these escapees being candidates for
      the phenotypic aberrations seen in polyX karyotypes. These escape genes have been
      reported to be under stronger purifying selection than other X-linked genes.
      Although it is known that escape from X-inactivation is much more common in
      humans than in mice, systematic assays of escape in humans have to date employed
      only interspecies somatic cell hybrids. Here we provide the first systematic next
      generation sequencing analysis of escape in a human cell line. We analyzed RNA
      and genotype sequencing data obtained from B lymphocyte cell lines derived from
      Europeans (CEU) and Yorubans (YRI). By replicated detection of heterozygosis in
      the transcriptome, we identified 114 escaping genes, including 76 not previously
      known to be escapees. The newly described escape genes cluster on the X
      chromosome in the same chromosomal regions as the previously known escapees.
      There is an excess of escaping genes associated with mental retardation,
      consistent with this being a common phenotype of polyX phenotypes. We find both
      differences between populations and between individuals in the propensity to
      escape. Indeed, we provide the first evidence for there being both hyper- and
      hypo-escapee females in the human population, consistent with the highly variable
      phenotypic presentation of polyX karyotypes. Considering also prior data, we
      reclassify genes as being always, never, and sometimes escape genes. We fail to
      replicate the prior claim that genes that escape X-inactivation are under
      stronger purifying selection than others.

PMID- 24023394
TI  - Frame rate free image velocimetry for microfluidic devices.
AB  - Here, we introduce Streamline Image Velocimetry, a method to derive fluid
      velocity fields in fully developed laminar flow from long-exposure images of
      streamlines. Streamlines confine streamtubes, in which the volumetric flow is
      constant for incompressible fluid. Using an explicit analytical solution as a
      boundary condition, velocity fields and emerging properties such as shear force
      and pressure can be quantified throughout. Numerical and experimental validations
      show a high correlation between anticipated and measured results, with R2 > 0.91.
      We report spatial resolution of 2 MUm in a flow rate of 0.15 m/s, resolution that
      can only be achieved with 75 kHz frame rate in traditional particle tracking
      velocimetry.

PMID- 24023395
TI  - Effect of Regular Exercise on the Histochemical Changes of d-Galactose-Induced
      Oxidative Renal Injury in High-Fat Diet-Fed Rats.
AB  - Renal lipid accumulation exhibits slowly developing chronic kidney disease and is
      associated with increased oxidative stress. The impact of exercise on the obese-
      and oxidative stress-related renal disease is not well understood. The purpose of
      this study was to investigate whether a high-fat diet (HFD) would accelerate d
      galactose-induced aging process in rat kidney and to examine the preventive
      effect of regular exercise on the obese- and oxidative stress-related renal
      disease. Oxidative stress was induced by an administration of d-galactose (100
      mg/kg intraperitoneally injected) for 9 weeks, and d-galactose-treated rats were
      also fed with a high-fat diet (60% kcal as fat) for 9 weeks to induce obesity. We
      investigated the efficacy of regular exercise in reducing renal injury by
      analyzing Nepsilon-carboxymethyllysine (CML), 8-hydroxygluanine (8-OHdG) and
      apoptosis. When rats were fed with a HFD for 9 weeks in d-galactose-treated rats,
      an increased CML accumulation, oxidative DNA damage and renal podocyte loss were
      observed in renal glomerular cells and tubular epithelial cells. However, the
      regular exercise restored all these renal changes in HFD plus d-galactose-treated
      rats. Our data suggested that long-term HFD may accelerate the deposition of
      lipoxidation adducts and oxidative renal injury in d-galactose-treated rats. The
      regular exercise protects against obese- and oxidative stress-related renal
      injury by inhibiting this lipoxidation burden. 

PMID- 24023396
TI  - Reassembly of anterior pituitary organization by hanging drop three-dimensional
      cell culture.
AB  - The anterior pituitary gland comprises 5 types of hormone-producing cells and non
      endocrine cells, such as folliculostellate (FS) cells. The cells form a lobular
      structure surrounded by extracellular matrix (ECM) but are not randomly
      distributed in each lobule; hormone-producing cells have affinities for specific
      cell types (topographic affinity), and FS cells form a homotypic meshwork. To
      determine whether this cell and ECM organization can be reproduced in vitro, we
      developed a 3-dimensional (3D) model that utilizes hanging drop cell culture. We
      found that the topographic affinities of hormone-producing cells were indeed
      maintained (ie, GH to ACTH cells, GH to TSH cells, PRL to LH/FSH cells). Fine
      structures in hormone-producing cells retained their normal appearance. In
      addition, FS cells displayed well-developed cytoplasmic protrusions, which
      interconnected with adjacent FS cells to form a 3D meshwork. In addition,
      reassembly of gap junctions and pseudofollicles among FS cells was observed in
      cell aggregates. Major ECM components-collagens and laminin-were deposited and
      distributed around the cells. In sum, the dissociated anterior pituitary cells
      largely maintained their in vivo anterior pituitary architectures. This culture
      system appears to be a powerful experimental tool for detailed analysis of
      anterior pituitary cell organization. 

PMID- 24023397
TI  - Neglected tropical diseases.

PMID- 24023398
TI  - Neglected communities.

PMID- 24023399
TI  - Treating neglected tropical diseases.

PMID- 24023401
TI  - Better sanitation, with communities taking the lead.

PMID- 24023400
TI  - Why water, sanitation and hygiene matter.

PMID- 24023402
TI  - Tackling worms in children: school programmes can work - for eyes too.

PMID- 24023403
TI  - Mapping neglected tropical diseases: a global view.

PMID- 24023405
TI  - Coming together to address neglected tropical diseases.

PMID- 24023404
TI  - A coordinated approach to mapping neglected tropical diseases.

PMID- 24023406
TI  - How to handle and care for bulbs in ophthalmic equipment.

PMID- 24023407
TI  - How to measure the pulse.

PMID- 24023408
TI  - Mass treatment for trachoma: how does it all work?

PMID- 24023409
TI  - Diagnose this.

PMID- 24023410
TI  - Clinical case study.

PMID- 24023413
TI  - Impact of the body mass on complications and outcome in multiple trauma patients:
      what does the weight weigh?
AB  - Obesity is known as an independent risk factor for various morbidities. The
      influence of an increased body mass index (BMI) on morbidity and mortality in
      critically injured patients has been investigated with conflicting results. To
      verify the impact of weight disorders in multiple traumatized patients, 586
      patients with an injury severity score >16 points treated at a level I trauma
      center between 2005 and 2011 were differentiated according to the BMI and
      analyzed regarding morbidity and outcome. Plasma levels of interleukin- (IL-) 6
      and C-reactive protein (CRP) were measured during clinical course to evaluate the
      inflammatory response to the "double hit" of weight disorders and multiple
      trauma. In brief, obesity was the highest risk factor for development of a
      multiple organ dysfunction syndrome (MODS) (OR 4.209, 95%-CI 1.515-11.692)
      besides injury severity (OR 1.054, 95%-CI 1.020-1.089) and APACHE II score (OR
      1.059, 95%-CI 1.001-1.121). In obese patients as compared to those with
      overweight, normal weight, and underweight, the highest levels of CRP were
      continuously present while increased systemic IL-6 levels were found until day 4.
      In conclusion, an altered posttraumatic inflammatory response in obese patients
      seems to determine the risk for multiple organ failure after severe trauma. 

PMID- 24023414
TI  - Prognostic value of inflammatory mediators in 1-year outcome of acute ischemic
      stroke with middle cerebral artery stenosis.
AB  - BACKGROUND AND PURPOSE: Inflammation exists in inception, progression, and
      reperfusion of acute ischemic stroke. Insightful understanding of correlation in
      inflammatory mediators and stroke severity with intracranial artery stenosis may
      improve rational stroke therapy. METHODS: We prospectively recruited 977 patients
      with acute noncardioembolic ischemic stroke with MCA stenosis by MRA as none to
      mild (<50%), moderate (50-69%), severe (70-99%), or occlusive (100%). The
      peripheral levels of WBC, homocysteine (HCY), and high sensitivity C-reactive
      protein (hs-CRP) were recorded. All patients were assessed of 1-year outcome by
      mRS as favorable (0-2) or poor (3-6). RESULTS: The levels of WBC, HCY, and hs-CRP
      had no significant differences in patients with categorized MCA stenosis (all P >
      0.05). Higher levels of WBC, HCY, and hs-CRP were found in patients with 1-year
      poor outcome (all P < 0.05), but only hs-CRP is an independent predictor (OR
      1.06, 95% CI 1.027-1.093, P = 0.0003). The combination of any two of increased hs
      CRP (>3 mg/L), WBC (>6.91 * 10(9)/L), and HCY (>15  MU mol/L) had higher power in
      predicting 1-year poor outcome than the single elevated mediator. CONCLUSIONS:
      Elevated hs-CRP independently predicts 1-year poor outcome in acute stroke. The
      combination of increased hs-CRP, WBC, or HCY had a stronger predictive value in
      poor outcome than individual elevated mediator.

PMID- 24023415
TI  - Molecule of the month: miRNA and Down's syndrome.

PMID- 24023416
TI  - Comparative insights using the molecular homology model of BDNF (Brain derived
      neurotrophic factor) of Varanus komodoensis and the known NGF (Nerve growth
      factor) structure of Naja atra.
AB  - BDNF (Brain derived neurotrophic factor) is a secretion protein and a member of
      the neurotrophin family of growth factors. Structural and functional
      characterization of BDNF Varanus komodoensis is of interest while its structure
      remains unknown. Thus, a homology molecular model of BDNF was constructed for
      gleaning possible structural insights. The model was compared with the structure
      of the homologous NGF (Nerve growth factor, another member of neuro-trophin
      family) from Naja atra. Comparative structural analysis of the models showed
      structural similarities with their predicted cavities for the interpretation of
      potential functional analogy. 

PMID- 24023417
TI  - Insights from the clustering of microarray data associated with the heart
      disease.
AB  - Heart failure (HF) is the major of cause of mortality and morbidity in the
      developed world. Gene expression profiles of animal model of heart failure have
      been used in number of studies to understand human cardiac disease. In this
      study, statistical methods of analysing microarray data on cardiac tissues from
      dogs with pacing induced HF were used to identify differentially expressed genes
      between normal and two abnormal tissues. The unsupervised techniques principal
      component analysis (PCA) and cluster analysis were explored to distinguish
      between three different groups of 12 arrays and to separate the genes which are
      up regulated in different conditions among 23912 genes in heart failure canines'
      microarray data. It was found that out of 23912 genes, 1802 genes were
      differentially expressed in the three groups at 5% level of significance and 496
      genes were differentially expressed at 1% level of significance using one way
      analysis of variance (ANOVA). The genes clustered using PCA and clustering
      analysis were explored in the paper to understand HF and a small number of
      differentially expressed genes related to HF were identified. 

PMID- 24023412
TI  - Immune privilege as an intrinsic CNS property: astrocytes protect the CNS against
      T-cell-mediated neuroinflammation.
AB  - Astrocytes have many functions in the central nervous system (CNS). They support
      differentiation and homeostasis of neurons and influence synaptic activity. They
      are responsible for formation of the blood-brain barrier (BBB) and make up the
      glia limitans. Here, we review their contribution to neuroimmune interactions and
      in particular to those induced by the invasion of activated T cells. We discuss
      the mechanisms by which astrocytes regulate pro- and anti-inflammatory aspects of
      T-cell responses within the CNS. Depending on the microenvironment, they may
      become potent antigen-presenting cells for T cells and they may contribute to
      inflammatory processes. They are also able to abrogate or reprogram T-cell
      responses by inducing apoptosis or secreting inhibitory mediators. We consider
      apparently contradictory functions of astrocytes in health and disease,
      particularly in their interaction with lymphocytes, which may either aggravate or
      suppress neuroinflammation. 

PMID- 24023418
TI  - Structure modeling and antidiabetic activity of a seed protein of Momordica
      charantia in non-obese diabetic (NOD) mice.
AB  - Momordica charantia is a well known medicinal plant used in the traditional
      medicinal system for the treatment of various diseases including diabetes
      mellitus. Recently, a novel protein termed as ADMc1 from the seed extract of M.
      charantia has been identified and isolated showing significant antihyperglycemic
      activity in type 1 diabetic rats in which diabetes was induced. However, the
      structure of this protein has not yet been analyzed. Homology modeling approach
      was used to generate a high quality protein 3D structure for the amino acid
      sequence of the ADMc1 protein in this study. The comparative assessment of
      secondary structures revealed ADMc1 as an all-alpha helix protein with random
      coils. Tertiary structure predicted on the template structure of Napin of B.
      Napus (PDB ID: 1SM7) with which the ADMc1 showed significant sequence similarity,
      was validated using protein structure validation tools like PROCHECK, WHAT_CHECK,
      VERIFY3D and ProSA. Arrangement of disulfide bridges formed by cysteine residues
      were predicted by the Dianna 1.1 server. The presence of multiple disulfide bond
      confers the stable nature of the ADMc1 protein. Further, the biological activity
      of the ADMc1 was assessed in non-obese diabetic (NOD) mice which are spontaneous
      model of type 1 diabetes. Significant reduction in the blood glucose levels of
      NOD mice was observed up to 8 h post administration of the rADMc1 protein.
      Overall, the structural characterizations with antihyperglycemic activity of this
      seed protein of Momordica charantia demonstrate its potential as an antidiabetic
      agent. 

PMID- 24023419
TI  - in-silico study of arylalkylamine-nacetyltransferase enzyme to regulate circadian
      rhythmicity.
AB  - Circadian Rhythmicity is present in the sleeping and breeding patterns of
      animals, including human beings and also related with brain wave activity,
      hormone production, cell regeneration and other biological activities. Melatonin
      is thought to play important roles in regulating circadian rhytmicity of the
      animals. Arylalkylamine-N-acetyltransferase (AANAT) is an enzyme which is
      responsible for the melatonin metabolism. In this study AANAT enzyme is targeted
      for the control of sleeping sickness and other irregular circadian rhythmicity by
      regulating the melatonin formation. AANAT protein 3D-structure was modeled,
      followed by loop modeling, refinement through energy minimization processes by
      molecular dynamics simulation and validation. Analysis of the Ramachandran plot
      shows 90.9% amino acids falls in the allowed region. The modeled protein was
      docked with N-Acetyl Serotonin. Combinatorial library was generated by using N
      Acetyl Serotonin as a reference molecule and molecules having 80% similarity to N
      Acetyl Serotonin was selected from Zinc database. These molecules were virtually
      screened by MOLEGRO virtual docker and top 5 molecules were selected and docked
      by using AutoDock. The AutoDock result shows that the ZINC01587152 molecule is
      having best interactions with the receptor protein. On the basis of this study we
      can suggest that the ZINC01587152 molecule is the best ligand against AANAT
      enzyme. It may be further synthesized and tested for sleep related disorders. 

PMID- 24023420
TI  - Design of inhibitors using a combinatorial library for HIV-Nef and human SH3
      domain interaction.
AB  - The HIV-1 Nef protein has the ability to down regulate important molecules at the
      immune synapse. These include class I and class II (Human Leukocyte Antigen) HLA
      on the Antigen Presenting Cells (APC). The receptors in these molecules consist
      of SH-3 domain and their interaction with the HIV-1 Nef is critical. Therefore,
      it is important to inhibit this HIV-Nef and human SH3 domain interaction. Thus,
      we used a combinatorial library to screen for molecules to inhibit this
      interaction. The exercise identified a group of top ranking compounds for further
      consideration. 

PMID- 24023421
TI  - Methylation impact analysis of erythropoietin (EPO) Gene to hypoxia inducible
      factor-1alpha (HIF-1alpha) activity.
AB  - Erythropoietin (EPO) is a glycoprotein hormone that play a role as key regulator
      in the production of red blood cells. The promoter region of EPO is methylated in
      normoxic (non-hypoxia) condition, but not in hypoxic condition. Methylation of
      the EPO enhancer region decline the transcription activity of EPO gene. The aim
      of this study is to investigate how different methylation percentage affected on
      the regulation and transcriptional activity of EPO gene. The DNA sequence of
      erythropoietin gene and protein sequence was retrieved from the sequence database
      of NCBI. DNA structure was constructed using 3D-DART web server and modeling
      structure of HIF1 predicted using SWISS-MODEL web server. Methylated DNA sequence
      of EPO gene using performed with YASARA View software and docking of EPO gene and
      transcription factor HIF1 analyzed by using HADDOCK webserver. Our result showed
      that binding energy in 46% methylated DNA was higher (-161,45 kcal/mol) than in
      unmethylated DNA (-194,16 kcal/mol) and 8% methylated DNA (-175,94 kcal/mol). So,
      we presume that a silencing mechanism of the Epo gene by methylation is
      correlated with the binding energy, which is required for interaction. A higher
      methylation percentage correlates with a higher binding energy which can cause an
      unstable interaction between DNA and transcription factor. In conclution,
      methylation of promoter and enhancer region of Epo gene leads to silencing. 

PMID- 24023422
TI  - Inferences from the ADMET analysis of predicted inhibitors to Follicle
      Stimulating Hormone in the context of infertility.
AB  - Follicle stimulating hormone (FSH) is a glycoprotein secreted by gonadotrophs of
      the anterior pituitary gland that regulates reproduction in mammals. FSH targets
      its receptor (FSHR) expressed only on grannulosa cells and induce the maturation
      of ovarian follicles in females. The levels of both FSH and FSHR rise until the
      middle of estrus cycle and then falls on level at the time of ovulation. It is
      associated with stimulated sertoli cell proliferation in testes and supports
      spermatogenesis in males. The interaction between the polypeptide FSH hormone and
      its corresponding receptor is highly selective. Therefore, it is of interest to
      inhibit FSH in the context of infertility. The structure of FSH (PDB ID: 1XWD) is
      screened using molecular docking techniques against the ZINC database (a database
      of 2.7 million compounds) with reference to known standard compounds. This
      exercise identifies compounds with better binding and ADMET (Absorption,
      Digestion, Metabolism, Excretion and Toxicity) properties compared to known
      standard compounds. These observations find application for the consideration of
      such compounds for further validation towards inhibiting the FSH. 

PMID- 24023423
TI  - in silico identification of cross affinity towards Cry1Ac pesticidal protein with
      receptor enzyme in Bos taurus and sequence, structure analysis of crystal
      proteins for stability.
AB  - Any novel protein introduced into the GM crops need to be evaluated for cross
      affinity on living organisms. Many researchers are currently focusing on the
      impact of Bacillus thuringiensis cotton on soil and microbial diversity by field
      experiments. In spite of this, in silico approach might be helpful to elucidate
      the impact of cry genes. The crystal a protein which was produced by Bt at the
      time of sporulation has been used as a biological pesticide to target the
      insectivorous pests like Cry1Ac for Helicoverpa armigera and Cry2Ab for
      Spodoptera sp. and Heliothis sp. Here, we present the comprehensive in silico
      analysis of Cry1Ac and Cry2Ab proteins with available in silico tools, databases
      and docking servers. Molecular docking of Cry1Ac with procarboxypeptidase from
      Helicoverpa armigera and Cry1Ac with Leucine aminopeptidase from Bos taurus has
      showed the 125(th) amino acid position to be the preference site of Cry1Ac
      protein. The structures were compared with each other and it showed 5% of
      similarity. The cross affinity of this toxin that have confirmed the earlier
      reports of ill effects of Bt cotton consumed by cattle. 

PMID- 24023424
TI  - Exploration of freely available web-interfaces for comparative homology modelling
      of microbial proteins.
AB  - AIM: This study was conducted to find the best suited freely available software
      for modelling of proteins by taking a few sample proteins. The proteins used were
      small to big in size with available crystal structures for the purpose of
      benchmarking. Key players like Phyre2, Swiss-Model, CPHmodels-3.0, Homer, (PS)2,
      (PS)(2)-V(2), Modweb were used for the comparison and model generation. RESULTS:
      Benchmarking process was done for four proteins, Icl, InhA, and KatG of
      Mycobacterium tuberculosis and RpoB of Thermus Thermophilus to get the most
      suited software. Parameters compared during analysis gave relatively better
      values for Phyre2 and Swiss-Model. CONCLUSION: This comparative study gave the
      information that Phyre2 and Swiss-Model make good models of small and large
      proteins as compared to other screened software. Other software was also good but
      is often not very efficient in providing full-length and properly folded
      structure.

PMID- 24023425
TI  - A new era of vitiligo research and treatment.

PMID- 24023426
TI  - Hypomelanoses in children.
AB  - Hypomelanosis of the skin is a frequently encountered problem in childhood, being
      totally innocent or representing the first sign of a multisystem disorder.
      Medical history, clinical examination, Wood's light investigation, histological
      analysis of the skin and a multidisciplinary consultation can contribute to a
      correct and early diagnosis of the different types of hypopigmentations. In the
      present paper, we present a systematic clinical approach to the differential
      diagnosis of those skin disorders. 

PMID- 24023427
TI  - A concise approach to childhood hypopigmentation.

PMID- 24023428
TI  - Stability in Vitiligo: Is there a Perfect Way to Predict it?
AB  - Stability is a hard-to-define concept in the setting of vitiligo, but is
      nonetheless extremely crucial to the planning of treatment regimens and also in
      prognosticating for the patient. There are several ways to judge stability in
      vitiligo, which include clinical features and, recently, many biochemical,
      cytological and ultrastructural correlates of the same. These recent advances
      help in not only in prognosticating individual patients but also in elucidating
      some of the mechanisms for the pathogenesis of vitiligo, including
      melanocytorrhagy and oxidative damage to melanocytes. 

PMID- 24023429
TI  - Grafting in vitiligo: how to get better results and how to avoid complications.
AB  - Grafting procedures in vitiligo have become quite popular over the last one or
      two decades especially in India. Starting with the simplest punch grafting we
      have now a multitude of different grafting techniques available in vitiligo. All
      of these grafting procedures are associated with certain complications. In
      addition there are certain factors and surgical pearls that can go a long way in
      improving the cosmetic results achieved with any of these grafting techniques.
      This paper will try to address these specific factors and complications
      associated with these grafting techniques and the ways and means to avoid them. 

PMID- 24023430
TI  - Depletion of CD200+ Hair Follicle Stem Cells in Human Prematurely Gray Hair
      Follicles.
AB  - INTRODUCTION: Melanocyte stem cells (MelSCs) are known to be depleted in gray
      hair follicles. Hair follicle stem cells (HFSCs) are important for maintenance of
      stemness of MelSCs. METHODS: We compared the proportion of CD200+ (Cluster of
      Differentiation 200 positive) stem cells in the outer root sheath cell suspension
      of gray and pigmented hair follicles of three patients with the premature graying
      of hair. In addition, explants culture for HFSCs was also carried out from gray
      and pigmented hair follicles. Cultured HFSCs were also differentiated into
      melanocytes. RESULTS: The mean +/- SD CD200+ HFSCs population were 9.4 +/- 1.4%
      and 3.5 +/- 0.5% for pigmented and gray hair follicles, respectively (P = 0.002).
      In explants culture, the growth of HFSCs from the gray hair follicle stopped at
      around day 20-22, whereas the growth of the cells from the pigmented follicle
      continued. CONCLUSION: CD200+ HFSCs are depleted in prematurely gray hair in the
      humans. CD200+ hair follicle stem cell yield is poorer in gray hair explant
      culture than pigmented hair explant culture.

PMID- 24023431
TI  - Depigmentation Therapy with Q-Switched Nd: YAG Laser in Universal Vitiligo.
AB  - BACKGROUND: Any residual pigment left in patients of universal vitiligo is
      managed with topical treatments, cryotherapy, and lasers. AIM: The study aims to
      assess the efficacy and safety of Q-switched Nd: YAG laser in treating the
      residual pigmentation in patients with universal vitiligo. MATERIALS AND METHODS:
      Fifteen patients of universal vitiligo with residual pigmentation on the face,
      hands, or feet, resistant to topical treatments, were treated with single or
      multiple sessions of Q-switched Nd: YAG laser treatment. Topical treatments were
      continued in between the laser sessions and the depigmentation achieved was
      monitored by clinical examination and repeat digital photographs. Response to the
      treatment was labelled as excellent if the residual pigment could be reduced by
      at least 90% while 50-90% resolution of pigmentation was labelled as a partial
      response. Adverse effects to the treatment offered were also monitored. RESULTS:
      Thirteen of the 15 patients enrolled for the study showed an excellent response
      to the treatment offered. Two other patients showed a poor response with less
      than 50% resolution of pigmentation. The number of laser sessions needed at a
      particular site ranged from 1 to 3 and no patient was offered more than three
      sessions of laser treatment at any site. No significant adverse events were
      reported by any patient. CONCLUSIONS: Residual pigmentation in patients with
      universal vitiligo that does not respond to topical treatment options alone can
      be managed quite effectively with Q-switched Nd: YAG laser without any
      significant adverse effects.

PMID- 24023432
TI  - Autologous platelet rich plasma in chronic venous ulcers: study of 17 cases.
AB  - BACKGROUND: Venous ulcers are wounds that are thought to occur due to improper
      functioning of venous valves, usually of the legs. They are the major cause of
      chronic wounds, occurring in 70% to 90% of chronic wound cases. The treatment of
      venous ulcers also entails substantial costs. Autologous platelet rich plasma
      (PRP) is a simple office based procedure which helps in enhancing the wound
      healing by releasing many growth factors like platelet derived growth factors,
      fibroblast derived growth factors and epidermal growth factors. AIM: To study the
      efficacy of autologous platelet rich plasma in the management of chronic venous
      ulcer. METHODOLOGY: 12 patients with 17 venous ulcers were treated with PRP and
      treatment outcome was measured by percentage of improvement in area and volume of
      the ulcer. RESULTS: 12 patients with 17 ulcers were treated with PRP. The mean
      age of the patients was 33.5 years (SD 9.82). 10 were males and 2 were females.
      The mean duration of the healing of the ulcers was in 5.1 weeks (SD 3.1). The
      mean percentage improvement in the area and volume of the ulcer was 94.7% (SD
      11.12) and 95.6% (SD 10.19) respectively. CONCLUSIONS: PRP is safe, simple and
      effective procedure in treating chronic venous ulcers.

PMID- 24023433
TI  - Direct hair transplantation: a modified follicular unit extraction technique.
AB  - BACKGROUND: In hair transplantation, the survival rate of harvested grafts
      depends upon many factors like maintenance of hydration, cold temperature,
      reduced mechanical handling and asepsis. All these factors are favourably
      improved if time out of body is reduced significantly. We have tried a
      modification called direct hair transplantation in the existing follicular unit
      extraction technique, in which the follicular unit grafts are implanted as soon
      as they are harvested. In this article, we have described the detailed
      methodology and a series of 29 patients who underwent direct hair
      transplantation. AIM: To evaluate the efficacy and feasibility of direct hair
      transplantation. SUBJECTS AND METHODS: The patients willing to undergo hair
      transplantation by the technique of follicular unit extraction were enrolled for
      the surgery. After administration of local anaesthesia, the recipient sites were
      created. Thereafter, the processes of scoring the skin with a motorized punch,
      graft extraction and implantation were performed simultaneously. These patients
      were followed up to look for the time period of initiation of hair growth, the
      growth achieved at the end of 6-8 months and any adverse events. The results of
      patients with noticeable improvement in the photographs and reduction in baldness
      grade were taken as 'good', whereas, in other patients, it was classified as
      'poor'. RESULTS: All patients were males with age ranging from 21 to 66 years
      (median 30 years). Twenty-six patients had androgenetic alopecia, 1 patient had
      traction alopecia and 2 patients had scarring alopecia. Twenty-seven patients
      showed 'good' results, whereas 2 patients showed 'poor' results. CONCLUSION:
      Direct hair transplantation is a simple and feasible modification in the
      follicular unit extraction technique. It is an efficacious surgical treatment
      modality for baldness.

PMID- 24023434
TI  - Direct Hair Transplantation (DHT): An Innovative Follicular Unit Extraction (FUE)
      Technique of Hair Transplantation.

PMID- 24023435
TI  - Patient profile and outcome of pilomatrixoma in district general hospital in
      United kingdom.
AB  - INTRODUCTION: A pilomatrixoma is a benign appendage tumour related to hair cells
      matrix. Most of the literature review about pilomatrixoma is in the form of case
      reports with fewer cohort studies. The objective of this cohort is to study the
      variable demographic characteristics, presentation and histopathology of this
      condition among a larger group of patients. MATERIALS AND METHODS: We conducted a
      retrospective study of patients who had excision of pilomatrixoma between
      February 1998 and August 2011 in a District General Hospital in UK. RESULTS: The
      study included 67 patients with histopathologically diagnosed pilomatrixoma. The
      mean age was 32 years. Male to Female ratio was 35:32. The average diameter of
      the lesion at presentation was 13 mm (range: 2-30 mm). 66 of 67 (98.5%) patients
      presented with solitary lesion, while 1 patient (1.5%) had two lesions.
      CONCLUSION: Pilomatrixoma is not an uncommon benign lesion. It is more common in
      the maxillofacial area.

PMID- 24023436
TI  - Body hair transplantation in vitiligo.
AB  - Hair transplantation has been used to repigment a stable vitiligo patch. Body
      hair transplant was done for a 28-year-old male with stable vitiligo with
      scarring. Peri-folllicular repigmentation was noted at 4 weeks and complete
      repigmentation of vitiligo patch was achieved at 12 weeks. No recurrence was
      noted at the end of 3-month follow-up with a good colour match with surrounding
      skin. To the best of our knowledge, this is the first case report highlighting
      the effectiveness of body hair transplantation by FUE in focal vitiligo patch
      with leukotrichia. 

PMID- 24023437
TI  - Body hair transplantation: case report of successful outcome.
AB  - Transplantation of body hair in to scalp has been suggested as an option to treat
      extensive cases of baldness with poor donor scalp. However, evidence about its
      long-term efficacy is yet lacking, with very few published reports and the
      routine use of the technique is still controversial. We report the satisfactory
      outcome in a case of extensive baldness in whom hairs from different donor areas
      such as chest, abdomen, arms, thighs were transplanted on to scalp. 

PMID- 24023438
TI  - Successful treatment of laser induced hypopigmentation with narrowband
      ultraviolet B targeted phototherapy.
AB  - Q-switched 1064 nm neodymium-doped yttrium aluminium garnet (Qs 1064 nm Nd: YAG)
      laser plays an important role in the treatment of pigmentary skin disorders,
      including tattoos. Although it has high efficacy and safety, adverse effect like
      hypopigmentation may occur causing anxiety to patients. We present a case report
      of Qs 1064 nm Nd: YAG laser induced hypopigmentation which was successfully
      treated with ultraviolet B targeted phototherapy, with rapid and satisfactory re
      pigmentation. 

PMID- 24023439
TI  - Successful Treatment of Laser Induced Hypopigmentation with Targeted Narrow Band
      UVB Therapy.

PMID- 24023441
TI  - Epidermal cell suspension: achieved by incubation at room temperature.

PMID- 24023440
TI  - Extracted hair follicle outer root sheath cell suspension for pigment cell
      restoration in vitiligo.
AB  - Vitiligo surgery has come up a long way from punch skin grafts to epidermal cell
      suspension and latest to the extracted hair follicle outer root sheath cell
      suspension (EHF-ORS-CS) transplantation. The progressive development from one
      technique to the other is always in a quest for the best. In the latest
      development- EHF-ORS-CS, which is an enriched source of follicular inactive
      melanocyte (melanocyte stem cells), seems to be a good addition to the prevailing
      cell-based therapies for vitiligo; however, need to be explored further in
      larger, and preferably randomized blinded studies. This review discusses the
      principle, technical details, and stem cell composition of hair follicular outer
      root sheath cell suspension. 

PMID- 24023442
TI  - Can Injectable Lignocaine be Replaced by Topical Anesthesia in Melanocyte
      Transplant or Ultrathin Skin Grafting?

PMID- 24023444
TI  - Evaluation of toxicity of 'Vatsanabha' (Aconitum ferox, Ranunculaceae) Before and
      After Shodhana.
AB  - Ayurvedic preparations contain toxic elements like heavy metals and other
      chemicals exceeding their permissible limits. Ayurvedic method of detoxification
      of such products involves Shodhana. Hence, in present paper it has been decided
      to replace Ayurvedic Shodhana process by chemical purification method and to
      study the benefits and/or drawbacks of the traditional Ayurvedic Shodhana
      process. Crude aconite root, Ayurvedic Shodhana treated aconite root and chemical
      Shodhana treated aconite root samples were evaluated for toxicity and changes by
      animal studies and thin layer chromatography (TLC) respectively. The results of
      the toxicity study suggest that the modified method of Shodhana is less efficient
      as compared to the traditional Ayurvedic Shodhana process. TLC studies have shown
      that pseudoaconitine and aconitine were converted into far less toxic substances
      like veratroyl pseudoaconine and benzoylaconine respectively only in traditional
      Ayurvedic Shodhana. 

PMID- 24023445
TI  - Anti-diabetic activity of active fractions of Stereospermum tetragonum DC and
      isolation of active principles.
AB  - OBJECTIVES: To identify the active principles, determine the anti-diabetes
      activity of fraction of Stereospermum tetragonum root. MATERIALS AND METHODS: The
      efficacy was evaluated in streptozotocin induced type 2 diabetic rats and the
      anti-hyperglycemic activity was studied by glucose tolerance test. The major
      active compounds were isolated by solvent fractionation and chromatographic
      techniques and characterized with spectral data. RESULTS: The active fraction of
      S. tetragonum showed presence of anti-diabetes mellitus activity in type-2
      diabetic rats. It did not significantly influence insulin release from cultured
      islets. Two active principles (active at 2 mg/kg dose) were isolated and
      characterized with spectral data. One of them was identified as an iridoid type
      glycoside and the other one was a lapachol like compound (derivative of
      naphthoquinone). CONCLUSIONS: Two active principles from the anti-diabetes
      fraction of S. tetragonum root were isolated and identified as an iridoid
      glycoside and a naphthoquinone derivative.

PMID- 24023446
TI  - Estimation of plasma levels of warfarin and 7-hydroxy warfarin by high
      performance liquid chromatography in patients receiving warfarin therapy.
AB  - Warfarin is one of the most commonly prescribed oral anticoagulant for prevention
      of thromboembolic events. The effect of this drug is measured by monitoring
      prothrombin time expressed as International Normalized Ratio (INR). In some
      cases, however, the measurement of plasma concentration of warfarin was
      emphasized. In the present study, reversed phase high performance liquid
      chromatography (HPLC) was used to estimate the plasma drug levels. A total of 185
      patients were enrolled in this study. Five milliliter of venous blood was
      collected using sodium EDTA tubes for pharmacokinetic analysis. Solid phase
      extraction was used to recover the warfarin and it's metabolite from plasma using
      isopropanol and potassium phosphate buffer (40:60) mobile phase. Warfarin, 7
      hydroxy warfarin and carbamazepine (internal standard) were separated on a C18
      column and had the retention time 3.6 min, 2.9 min and 5.9 min, respectively. The
      assay was linear in warfarin concentration ranges of 0.1-5 MUg/ml. The extraction
      recovery was found to be ?85%. The mean plasma concentrations of warfarin and 7
      hydroxy warfarin were found to be 3.47 +/- 1.87 (SD) MUg/ml, 1.25 +/- 0.81 (SD)
      MUg/ml, respectively. Through the present study the plasma concentrations of
      warfarin, 7-hydroxy warfarin and their metabolic ratio was determined. The assay
      was sensitive to follow warfarin pharmacokinetics in a patient with warfarin
      therapy for 3 months and above. 

PMID- 24023447
TI  - Clopidogrel and the possibility of drug-drug interaction in primary health care.
AB  - INTRODUCTION: Clopidogrel ineffectiveness is a serious problem in antiplatelet
      therapy. Many factors may contribute to this phenomenon. One of them is
      clopidogrel drug-drug interaction with CYP2C19 and CYP3A4 enzyme inhibitors. The
      main goal of this descriptive study was to assess the prevalence of cases of
      clopidogrel-drug interactions in the primary health care physicians' practices.
      MATERIALS AND METHODS: During 2010-2011, 80 patients receiving clopidogrel
      antiplatelet therapy from primary care physicians' clinical practices were
      involved in this study. By using questionnaires and case histories, the following
      information was collected: Age, gender, clinical diagnoses, and medications used.
      RESULTS: IN THE CURRENT STUDY, DRUGS WERE USED THAT COULD POTENTIALLY INFLUENCE
      THE EFFECT OF CLOPIDOGREL: Omeprazole, lipophilic statins, calcium channel
      blockers (CCB). There was a different use of the above-mentioned drugs before and
      after the initiation of the clopidogrel therapy, e.g., 12 (15.0%) and 44 (55.0%)
      patients used proton pump inhibitors (PPI) before and after the clopidogrel
      therapy accordingly (P = 0.16; chi (2) = 1.91). However, pantoprazole was
      recommended more often than other PPI. The use of the potential CYP3A4 inhibitors
      - lipophilic statins and CCB - was increased after the prescription of
      clopidogrel too. Concomitant use of statins (mainly atorvastatin) with
      clopidogrel was observed in 75 (93.8%) patients and the use of CCB (mainly
      amlodipine) - in 33 (41.3%) patients. CONCLUSION: In the primary health care
      practices, it is revealed that there is co-medication of clopidogrel with weak
      CYP3A4 inhibitors, such as lipophilic statins and amlodipine, and with the
      moderate CYP2C19 inhibitor - omeprazole. The latter co-medication is potentially
      harmful and it is very important to inform the first care professionals about the
      opportunity to change omeprazole to pantoprazole, which does not influence
      clopidogrel biotransformation.

PMID- 24023448
TI  - Compilation of a herbal medicine formulary for herbal substances in Malta and its
      usefulness amongst healthcare professionals.
AB  - CONTEXT: Today, the use of herbal medicine for primary healthcare has increased
      considerably. Since local pharmacists graduate with little knowledge on herbal
      medicine, the majority are ill-equipped to provide pharmaceutical advice. AIMS:
      To develop and evaluate a herbal medicine formulary to aid healthcare
      professionals (HCPs) in the prescribing, dispensing and counselling
      responsibilities. SETTINGS AND DESIGN: Community pharmacies. METHODS AND
      MATERIAL: Monographs on all herbal substances available locally were compiled
      into a formulary. The formulary was then distributed to all, 216, local
      pharmacies. Subsequently, a questionnaire was distributed to 55 pharmacists and
      10 general practitioners (GPs). STATISTICAL ANALYSIS USED: Descriptive
      statistical analysis. RESULTS: A total of 177 herbal monographs have been
      compiled and 612 herbal products listed. Thirty HCPs participated in the
      questionnaire. The formulary was found to be useful by all participants with 19
      claiming to use it frequently and 7 quite frequently. Participants (n = 30) agree
      that the information contained within the formulary was found to be useful (26),
      the formulary helped them learn which HMPs are present in the local market (29),
      the formulary is user friendly (27), information included is up-to-date and well
      referenced (29) and that there is the need for a formulary of this kind in Malta
      (28). CONCLUSIONS: The formulary was found to be a useful tool for HCPs leading
      to high quality, evidence-based prescribing together with enhanced monitoring and
      improved patient care.

PMID- 24023449
TI  - Development and validation of RP-HPLC-UV method for the determination of
      Glipizide in human plasma.
AB  - A simple, sensitive and selective HPLC method with UV detection for determination
      of Glipizide in human plasma was developed. Liquid-liquid extraction method was
      used to extract the drug from the plasma samples. Chromatographic separation of
      Glipizide was achieved using C18 column (ZORBAX ODS 4.6 * 150 mm). The mobile
      phase was comprised of 0.01 M potassium dihydrogen phosphate and acetonitrile
      (65:35, v/v) adjusted to pH 4.25 with glacial acetic acid. The analysis was run
      at a flow rate of 1.5 mL/min with an injection volume was 20 MUL. The detector
      was operated at 275 nm. The calibration curve was linear over a concentration
      range of 50-1600 ng/mL. Intra-day and inter-day precision and accuracy values
      were below 15%. The limit of quantification was 50 ng/mL and the mean recovery
      was above 98%. Freeze-thaw, short-term, long-term and post-preparative stability
      studies showed that Glipizide in plasma sample was stable. The method may be
      successfully applied to analyze the Glipizide concentration in plasma samples for
      bioavailability and bioequivalence studies. 

PMID- 24023450
TI  - Topiramate: Safety in migraine patients.

PMID- 24023451
TI  - Faculty outlook toward animal experiments in post-graduate medical education.

PMID- 24023452
TI  - The changing face of pharmacy practice and the need for a new model of pharmacy
      education.
AB  - Pharmacy profession has evolved from its conventional and traditional drug
      focused basis to an advanced patient focused basis over the years. In the past
      century the pharmacists were more involved in compounding and manufacturing of
      medicines, but this role has significantly reduced over time. This advancement in
      the role of pharmacist calls for them to be the part of the broader health care
      team working for providing better health care for the patients, thus contributing
      in achieving the global millennium development goals. To match up, the role of
      today's pharmacists needs to be expanded to include pharmaceutical care concepts,
      making the pharmacist a health care professional rather than a drug seller in a
      commercial enterprise. Therefore, pharmacy schools should prepare a program that
      has competence with the changing role of the pharmacist. The education should
      provide ability for critical thinking, improve problem-solving skills and
      decision making during pharmacotherapy. The student should be trained to create,
      transmit, and apply new knowledge based on cutting-edge research in the
      pharmaceutical, social, and clinical sciences; collaborate with other health
      professionals and learn to enhance the quality of life through improved health
      for the people of local society and as well as the global community. 

PMID- 24023453
TI  - An in silico approach to design potential siRNA molecules for ICP22 (US1) gene
      silencing of different strains of human herpes simplex 1.
AB  - BACKGROUND: The herpes simplex virus (HSV-1) is a virus that manifests itself in
      viral infection with painful, watery blisters in the skin or on the genitals as
      well as mucous membrane such as the mouth or lips. During an outbreak, the
      disease is contagious particularly and is irredeemable with present technology.
      Genetic studies of HSV-1 have shown that ICP22 (US1) gene is an immediate early
      gene and is responsible for genome replication and also has contribution in viral
      infection. METHOD: For disease diagnosis, ICP22 (US1) gene may be suitable
      target. Viral activity can be controlled through RNA interference technology, a
      significant method for the post-transcriptional gene silencing. However, in
      different viral isolates there is a genetic variability; it is very challenging
      to design possible siRNA molecules which can silence the respective target genes.
      The work was done by using various computational tools as similarity search,
      target alignment, secondary structure prediction and RNA interaction evaluation.
      RESULT: In our study two effective siRNA molecules for ICP22 (US1) gene silencing
      of seven different strains of HSV-1 were rationally designed and authenticated
      using computational methods, which might lead to knockdown the viral activity.
      CONCLUSION: siRNA molecules were foreseen against ICP22 (US1) gene of different
      strains of HSV-1 as effective aspirant using computational methods. Thus, the
      approach may deliver a vision for the chemical synthesis of antiviral RNA
      molecule for treatment of HSV-1, at genomic level.

PMID- 24023454
TI  - Reasons of using complementary and alternative medicines (CAM) among elderly
      Malaysians of Kuala Lumpur and Selangor states: An exploratory study.
AB  - BACKGROUND: This study is aimed to explore the types of CAM and reasons of using
      CAM among elderly Malaysians. METHOD: This cross-sectional study was conducted on
      a sample of 256 conveniently selected elderly Malaysians who were residing in the
      states of Selangor and Kuala Lumpur. A pre-validated interview-administered
      questionnaire was used to gather information. Data was entered into PASW version
      18 and analyzed. RESULTS: A total of 256 questionnaires were included in the
      study. A response rate of 64% was achieved. Out of 256 respondents, 92 (35.9%)
      were male while 164 (64.1%) were female. More than half of the respondents (n =
      141; 55.1%) agreed that CAM is more effective than allopathic medicine. Chinese
      respondents showed strong belief in the effectiveness of CAM. In terms of safety
      of CAM, close to three quarters of respondents (n = 178; 69.5%) believed that CAM
      is safer than allopathic medicine. A large majority of respondents agreed that
      CAM has less side effects compared to allopathic medicine (n = 201; 78.5%) and
      also agreed that CAM is good to maintain overall health and wellbeing (n = 212;
      82.8%). A majority of the respondents expressed that they use CAM because
      allopathic medicine is less effective (n = 113; 44.1%). CONCLUSION: The current
      study reflects the reasons of using CAM among lay public from different
      ethnicities. There are no reports of adverse effects related to CAM use. Future
      approaches should be intended for awareness campaigns for consumers, highlighting
      safety profile of CAM and as well as forbidding their use without the
      consultation of healthcare professional.

PMID- 24023455
TI  - Pharmacognostic standardization, antioxidant and free radical scavenging activity
      of the seeds of Triticum aestivum L - A dietary staple.
AB  - AIMS: To establish the Quality standards of Triticum aestivum L, seeds as per WHO
      guidelines. To study the antioxidant and hepatoprotective profile of T. aestivum
      L. seeds. METHODS: Pharmacognostic studies like morphological, microscopical,
      physico-chemical, phytochemical evaluation, fluorescence analysis, TLC, HPTLC,
      phytochemical analysis etc. of various extracts of the seeds of T. aestivum were
      carried out as per established methods. The ethanolic extract was evaluated for
      antioxidant and hepatoprotective activity using rat model. RESULTS: Preliminary
      phytochemical analysis mainly revealed the presence of carbohydrates, phenolics,
      proteins, resins, lipids and flavonoids. T. aestivum at different doses, i.e. 5
      45 MUg/ml showed free radical scavenging activity in dose dependent manner. The
      amount of phenolic components was found to be 313.5 MUg/mg indicating
      considerable antioxidant activity. The ethanolic extract of T. aestivum was
      administered at dose level of 100 mg/kg/day, every day for 21 days along with
      CCl4. Biochemical and histopathological results conclude that the seeds have
      hepatoprotective activity.

PMID- 24023456
TI  - Inverted U shaped effect of nicotine on the severity of depressive symptoms: A
      population-based survey.
AB  - OBJECTIVES: To investigate whether that nicotine concentration represented by the
      degree of smoking dependence variably influence the rate and severity of
      depressive symptoms. METHODS: Cross-sectional, analytical study, involving 300
      medical students selected by random sampling techniques were asked to complete a
      questionnaire contains three parts: demographic information, Beck Depression
      Inventory with cutoff point for depression is 17 and the Fagerstrom Test for
      Nicotine dependence with cutoff point for severe dependence is five. RESULTS: A
      total of 233 medical students completed the questionnaire; their mean age was
      (21.38 +/- 1.74). The rate of smoking was 22.7% while that of depression was
      32.2%. Low dependent smokers in contrast to other groups of smokers and non
      smokers display the lowest rate of depressive symptoms (15%), while the highest
      rate recorded among severely dependent smokers (71.4%, p = 0.0001). After
      adjustment of other risk factors, regression analysis reveal that severe
      dependent smokers associated with 12.5 odds of depressive symptoms than non
      smokers (p = 0.0001, C.I. 4.10-38.29). CONCLUSION: In comparison with light and
      moderate smokers, heavy smokers demonstrate higher risk of depressive symptoms in
      medical students.

PMID- 24023457
TI  - A case of montelukast induced hypercholesterolemia, severe hypertriglyceridemia
      and pancreatitis.
AB  - Montelukast sodium is a leukotriene inhibitor, and competitively antagonizes cys
      LT1 receptor and used widely and effectively in treating allergic rhinitis,
      bronchial asthma and allied respiratory conditions. This case report outlines a
      rare case of montelukast induced hypercholesterolemia, severe
      hypertriglyceridemia and acute pancreatitis in a 22 years old male patient. The
      patient was taking 10 mg oral montelukast daily for allergic rhinitis. Although
      his symptoms improved considerably, after 2 months of therapy, he experienced
      unusual weight gain and got admitted with severe pain abdomen. Clinical and other
      relevant investigation findings revealed the presence of acute pancreatitis with
      associated hypercholesterolemia and severe hypertriglyceridemia. There were no
      evidences of any other possible hereditary, surgical, metabolic, infective,
      organic or other pathologic causes giving rise to these conditions. De-challenge
      was done and the patient was treated conservatively resulting in reversal of the
      diseased state. Naranjo adverse drug reaction probability scale suggested that it
      was 'probable' that oral administration of montelukast was responsible for the
      acute pancreatitis associated with hypercholesterolemia and severe
      hypertriglyceridemia. There is only a singular and confirmed reported case of
      montelukast induced hypertriglyceridemia from India. For patients taking
      montelukast for a long duration, routine lipid profile monitoring should be done,
      and if these patients present with symptoms of epigastric and periumbilical pain
      with vomiting, provisions for screening acute pancreatitis might be warranted. 

PMID- 24023458
TI  - A summary report of the workshop on the 'academic leadership training in the
      AIMST University, Malaysia'.
AB  - In Malaysia, there are 81 (as on February 15, 2013) higher education institutions
      including satellite branches of the foreign universities. In northern part of the
      Peninsular Malaysia, AIMST University is the first private not-for-profit
      university and aims to become a premier private university in the country and the
      region. The workshop described in this article was designed to develop and
      enhance the capacity of academic staff-in-leadership-role for the University.
      This type of workshops may be a good method to enhance the leadership qualities
      of the head of each unit, department, school and faculty in each university. 

PMID- 24023459
TI  - Sensitive polarographic electrochemical determination of clarithromycin in blood
      serum.
AB  - Clarithromycin is an antibacterial widely used for the treatment of a myriad of
      infections. Various methods including HPLC have been reported for its drug plasma
      concentration but they are more complex. In this study, we developed an
      electrochemical method for estimation of clarithromycin in blood using
      differential pulse polarography (DPP) after oral administration of pure
      clarithromycin suspension. The differential pulse polarography of clarithromycin
      showed peak with peak potential Ep is -1460 mV SCE at pH 6.5 +/- 0.1. The
      developed electrochemical method was standardized and validated for the
      determination of clarithromycin in blood serum of albino rats. PK analysis
      included C max, T max, AUC0-24, elimination rate constant (Kel) and t1/2. C max
      were found to be 1.34 +/- 0.16 mg/ml and 1.99 +/- 0.22 mg/ml for plain
      clarithromycin and suspension formulation, respectively. Effects of ammonium
      tartarate concentration and pH were also studied as specificity parameters.
      Developed electrochemical method was found to be simple, accurate method for to
      estimate blood-clarithromycin profile and can also be used similarly for various
      dosage forms. 

PMID- 24023460
TI  - Is there a need for a formulary of clinically interchangeable medicines to guide
      generic substitution in Saudi Arabia?
AB  - The escalating healthcare expenditure is a major challenge to sustainability of
      the healthcare systems. To confront the escalating health expenditure in general
      and medicines expenditure in particular, many countries promoted the use of
      generic medicines. To promote generic medicines, many countries have adopted a
      generic substitution (GS) policy and generic prescribing. To effectively
      implement the GS policy, it is evident in the literature that it is essential to
      have an evidence-based guide on therapeutic equivalence and formulary of
      interchangeable medicines to guide responsible GS. In Saudi Arabia, GS is
      permissive and pharmacists are given the right to perform GS. While the
      prescriber's approval is not a requirement, patient consent is required when
      performing GS. Although there are some general drug references, such as the Saudi
      National Formulary (SNF) and list of registered medicines in the Saudi market,
      but there is currently no information available to healthcare professionals that
      documents the therapeutic and bioequivalence between medicines. Thus, it is
      essential to have a formulary of interchangeable medicines to guide appropriate
      GS or at least to include such vital information regarding therapeutic
      equivalence and brand interchangeability as part of the SNF. That, in turn, will
      not only make healthcare professionals more confident when providing GS, but will
      also enable the avoidance of situations where GS is inappropriate. 

PMID- 24023462
TI  - Early detection of C-reactive protein and von Willebrand factor levels in
      Malaysian patients with acute coronary syndrome.
AB  - BACKGROUND: Diagnosing acute coronary syndrome (ACS) remains a challenge in
      patients presenting at early phase of hospitalization. We hypothesized that
      inflammatory markers of plaque rupture could accurately identifying ACS patients
      from stable coronary artery diseases (CAD). MATERIALS AND METHODS: The serum and
      peripheral blood gene expression levels of C-reactive protein (CRP) and von
      Willebrand factor (vWF) in multiethnic Malaysian patients (n = 7) admitted with
      early hospitalization of ACS was evaluated. Nine patients with stable coronary
      artery disease without previous history of ACS were enrolled as controls.
      RESULTS: Serum and peripheral blood mRNA levels of CRP and vWF were significantly
      higher in ACS compared to control groups (P < 0.05). CONCLUSIONS: Elevated levels
      of these markers in ACS may reflect an acute phase response due to endothelial
      dysfunction. Both CRP and vWF may add to the list of useful markers for early
      detection of ACS in hospitals of developing countries.

PMID- 24023463
TI  - Prevalence and significance of electrocardiographic changes and side effect
      profile of regadenoson compared with adenosine during myocardial perfusion
      imaging.
AB  - BACKGROUND: Significance of electrocardiogram (EKG) changes associated with
      regadenoson as well as side effects compared to adenosine in a real world,
      unselected population is unknown. METHODS AND RESULTS: Three hundred ninety six
      consecutive patients undergoing either adenosine or regadenoson-based single
      isotope (Technetium 99c) nuclear images were evaluated. A standard form
      documenting side effects was filled immediately following administration. The
      EKGs and nuclear scans were reviewed in a blinded-fashion. Commonest symptoms
      reported were flushing (64%), chest pain (36%) and dyspnea (36%). Flushing and
      chest pain were significantly more common with adenosine (73% vs. 57%, P < 0.01
      and 53% vs. 47%, P = 0.06) and dyspnea more with regadenoson (40% vs. 31%, P =
      0.05). Sixty (29%) patients carried a diagnosis of chronic bronchitis or asthma
      but only 4 (2 with each) required aminophylline. There was no significant
      correlation between chest pain induced by either agent or ischemia on nuclear
      imaging. EKG changes occurred infrequently (16% with regadenoson and 10% with
      adenosine), and had low sensitivity for detecting ischemia (7% for regadenoson
      and 11% for adenosine). CONCLUSIONS: EKG changes with adenosine and regadenoson
      occur infrequently and have low sensitivity for detecting ischemia. Chest pain is
      frequently induced by both, and is not predictive of ischemia on nuclear imaging.

PMID- 24023464
TI  - Prevalence of rheumatic and congenital heart disease in school children of Andhra
      Pradesh, South India.
AB  - OBJECTIVE: To determine the prevalence of rheumatic heart disease (RHD) and
      congenital heart disease (CHD) using clinical and echocardiographic criteria in
      rural and urban school children in Andhra Pradesh, South India. MATERIALS AND
      METHODS: A total of 4213 school children between 5 and 16 years of age were
      screened. 1177 were from rural schools and 3036 from urban schools. Prevalence of
      RHD and CHD was estimated. RESULTS: Clinically RHD was present in 3 (prevalence
      0.7/1000). Using echocardiography RHD was detected in 32 (7.6/1000), 11
      (7.3/1000) from rural and 21 (7/1000) from urban schools. (P = 0.000, O.R = 0.093
      and C.I. = 0.023-0.317). Total prevalence of RHD is 8.3/1000. Clinically CHD was
      present in 39 (9.2/1000) children, rural 9 (7.6/1000) and urban 30 (9.9/1000).
      Using echocardiography CHD was detected in 44 (10.4/1000) children, rural 11
      (9.3/1000) and urban 33 (10.8/1000). CONCLUSION: RHD was detected several fold
      using echocardiographic screening than by clinical examination alone.
      Longitudinal follow-up of children with echocardiographically diagnosed
      subclinical RHD is needed.

PMID- 24023465
TI  - Relationship between coronary artery stenosis and cardio-ankle vascular index
      (CAVI) in patients undergoing cardiovascular surgery.
AB  - BACKGROUND: The cardio-ankle vascular index (CAVI) was developed as an indicator
      of arterial wall stiffness, and it is less influenced by blood pressure (BP). We
      investigated the relationship between the CAVI and coronary artery disease (CAD),
      and evaluated the effects of rapid changes in BP induced by anesthetics on CAVI.
      MATERIALS AND METHODS: We measured the CAVI in 76 patients before and after the
      administration of anesthetics for elective cardiovascular surgery. The patients
      were assigned to groups with or without CAD (0VD). The CAD group was then divided
      into 3 subgroups based on the number of stenotic vessels (1VD, 2VD, and 3VD). We
      compared the CAVI between CAD and 0VD, and changes in BP during the induction of
      anesthesia. All data were analyzed using Stat View 5.0 software. RESULTS:
      Systolic BP significantly decreased from 145 +/- 21 to 107 +/- 20 mmHg, whereas
      CAVI was not altered after the administration of intravenous anesthetics. Changes
      in BP and in pre-anesthetic CAVI (pre-CAVI) did not correlate. The pre- and post
      anesthetic values for the CAVI (post-CAVI) in the 0VD and CAD groups were 8.34 +/
      1.01 and 8.44 +/- 1.39, and 9.95 +/- 1.22 and 10.12 +/- 1.56, respectively. Both
      values were higher in the CAD, than in the 0VD group (P < 0.05). CONCLUSION: The
      CAVI is independent of BP and reproducible regardless of the induction of
      anesthesia and is significantly higher in patients with CAD. The CAVI might be
      able to predict atherosclerosis and coronary artery stenosis in patients
      undergoing cardiovascular surgery.

PMID- 24023466
TI  - Effect of omega-3 on brain natriuretic peptide and echocardiographic findings in
      heart failure: Double-blind placebo-controlled randomized trial.
AB  - BACKGROUND: Possible beneficial effects of dietary omega-3 supplementation on
      patients with congestive heart failure (CHF) were investigated. METHODS AND
      RESULTS: 100 patients with CHF who had a tri-chamber pacemaker and automated
      defibrillator were initially recruited, and 70 agreed to participate.38 patients
      received 2 g/day of omega-3 and 32 received placebo capsules. BNP level, 6-min
      walk test and echocardiographic parameters were recorded at baseline and after 6
      months of treatment. BNP levels decreased significantly after 6 months in the
      omega-3 group, from 1766.2 +/- 1978.1 pg/mL to 1159.4 +/- 1430.9 pg/dL (P <
      0.005). Tei index and late diastolic velocity index were significantly improved
      in treated group. Mortality and hospitalization rates did not differ. CONCLUSION:
      The beneficial effects of omega-3 supplementation in patients with CHF were not
      as clear as hypothesized; however, omega-3 fatty acids can result in small
      changes in plasma BNP levels and modest improvements in echocardiographically
      assessed diastolic function (Clinical trial.gov registration: NCT01227837).

PMID- 24023467
TI  - Rheumatic heart disease in rural south India: A clinico-observational study.
AB  - BACKGROUND: Rheumatic heart disease (RHD) is still a public health issue in many
      countries in the world, and particularly in Southeast Asia. India, for example,
      contributes 25%-50% of the global burden of RHD. Clinic-based and epidemiological
      studies on RHD in India have used different methodologies and clinical criteria
      to estimate RHD burden in India. The present study employs strict clinical
      criteria, including echocardiography, to estimate RHD prevalence and associated
      clinical complications in a large unique rural population in southern India
      covered through a governmental health insurance scheme. MATERIALS AND METHODS:
      Total 44,164 eligible patients were screened from 238 primary care health centers
      in rural southern India between October 2007 and March 2012 using strict clinical
      criteria and objective ascertainment. A total of 403 patients aged 15 years or
      above were finally analyzed based on both the inclusion and exclusion criteria.
      Detailed information on both demographic and clinical characteristics was
      obtained through personal interviews and clinical examinations. Descriptive
      analyses were performed, including age standardization. RESULTS: The age
      standardized RHD prevalence rate was 9.7/1000 populations-more common in younger
      age groups (<44 years) and relatively high among females. Pulmonary hypertension
      was the most common clinical complication followed by CHF, tricuspid
      regurgitation, as well as infective endocarditis. More than two-thirds had no
      past history of RHD or penicillin prophylaxis. CONCLUSIONS: RHD rates are still
      high in rural India among populations covered through governmental health
      insurance scheme. Both primary and secondary preventive measures, including
      widespread coverage of penicillin prophylaxis, must be considered mainstay tools
      to both prevent and reduce RHD burden in endemic populations, including rural
      India.

PMID- 24023468
TI  - Influence of education in the prevalence of obesity in Iranian northern adults.
AB  - BACKGROUND: The main aim of this study was to evaluate whether prevalence of
      obesity in educational levels is different and some related factors in Iranian
      northern adults. MATERIALS AND METHODS: This was a cross-sectional descriptive
      study based on population and 2452 cases (1224 men and 1228 women) aged 15-65
      years were chosen by cluster and stratify sampling. Subjects were randomly chosen
      from 125 clusters and each cluster included 20 cases. Interviewers recorded the
      data using a multidimensional questionnaire including socio-demographic indexes.
      RESULTS: As a whole, the prevalence of obesity was seen in 24% of subjects (15.5%
      in male and 32.5% in female) and significantly was seen in 3.1% and 14.1% of
      uneducated people more than in 1-9 year schooling and in high school or college
      educated people, respectively (P = 0.001). The risk of obesity was 2.294 (P =
      0.001) in uneducated compared to high school or college-educated people, 1.668 (P
      = 0.001) in urban area compared to rural area, 2.619 (P = 0.001) in 40-65 year
      people compared to 15-40 year people, and 1.534 (P = 0.003) in good economic
      compared to poor economic groups. After adjusted for location area, gender, age,
      and economic stats, the risk of obesity was 2.044 (P = 0.001) in uneducated
      people compared to high school or college-educated subjects. CONCLUSION: The
      obesity as a health problem in Iranian northern adults supported in this study
      and it was negatively associated with educational levels. Public health programs
      that aim to reduce obesity should primarily focus on the illiterate and low
      educated people.

PMID- 24023469
TI  - Congenital cardiac anomalies and imperforate anus: A hospital's experience.
AB  - OBJECTIVES: We aimed in our study to determine the incidence and type of
      congenital cardiac anomaly (CCA) in newborns associated with imperforate anus
      (IA), the outcome of surgical reconstruction of the anorectum in our center, and
      the need for performing echocardiography in all patients with IA. MATERIALS AND
      METHODS: The preoperative echocardiography reports of all cases born with IA and
      managed at King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a period
      of 11 years (Jan 2000-Dec 2010) were reviewed. The average annual delivery rate
      of this hospital is 5500. RESULTS: During the study period, 61 patients of IA
      were diagnosed that showed an incidence of about 1 per 992 live births, and the
      rate of CCA among the IA subjects was 15 (24.6%). In 12 patients (19.6%), the
      associated CCAs were of a mild nature, and reconstruction of the anorectum went
      smoothly. Three patients (4.9%) had significant CCA and died. CONCLUSION: The
      incidence of IA in our hospital is 1 per 992 live births, and its association
      with CCA is 24.6%. The majority of CCAs associated with IA were of the mild type.

PMID- 24023470
TI  - Microalbuminuria and C-reactive protein as a predictor of coronary artery disease
      in patients of acute chest pain.
AB  - Microalbuminuria is a risk factor for cardiovascular disease. It is gaining
      importance as a marker of atherogenic milieu and indicates the target organ
      damage and can be a valuable tool in screening and identification of patients
      with cardiovascular disease. Markers of inflammation, such as C-reactive protein
      (CRP), were found to be related to cardiovascular disease (CVD) events in
      patients with chest pain. In addition, recent studies have shown that, in the
      case of atherosclerosis, increased levels of CRP, reflects inflammatory condition
      of vessel wall. In the present study, CRP and microalbuminuria were estimated in
      patients of acute chest pain. The patients were divided into two study groups (gp
      1 patients of chest pain with CVD and gp-2 patients of chest pain of causes other
      than CVD) along with one healthy control group. It was found that
      microalbuminuria was higher in CVD patients (RR = 6.250,95% CI 2.346-16.45,P <
      0.05) and also CRP was much higher in CVD patients (RR = 13.667,95% CI 4.528
      41.253, P < 0.05) as compared to other two groups. Sensitivity, specificity and
      positive predictive value of CRP and microalbuminuria were also higher in gp-1
      (CVD) patients as compared to other two groups. Therefore, CRP and
      microalbuminuria can be used as important biomarkers in screening CVD. 

PMID- 24023471
TI  - Comparison of non-invasive diagnostic tests to multi-detector CT pulmonary
      angiography for the diagnosis of pulmonary embolism.
AB  - CONTEXT: Acute pulmonary embolism (PE) remains a diagnostic and therapeutic
      challenge to physicians. There are various non-invasive diagnostic modalities
      been suggested to diagnose pulmonary embolism. AIM: We tried to find the
      performance of various non-invasive investigations in comparison to multi
      detector Computerized Tomography (MDCT pulmonary angiography for the diagnosis of
      PE). SETTINGS AND DESIGN: A prospective cohort study was conducted in 80
      hospitalized medical patients. MATERIALS AND METHODS: There were 80 patients with
      Wells score > 2 who were included. The demographic data, non-invasive
      investigations, and MDCT pulmonary angiography were conducted in these patients.
      The sensitivity (SEN), specificity (SPE), positive predictive value (PPV), and
      negative predictive value (NPV) were calculated for each test. RESULTS: Out of 80
      patients, 77.5% patients were with Wells score 3-6 and 22.5% patients were with
      Wells score more than 6. The test with highest sensitivity was d-dimer (SEN -
      90%, P = 0.091) followed by PAH on TTE (SEN - 83%, PPV - 86%, P = 0.006). The
      most specific test was ECG showing S1Q3T3 (SPE - 100%, P = 0.421), followed by
      Wells score > 6 (SPE - 91%, P = 0.211). There was no test with sensitivity and
      specificity more than 90% CONCLUSION: In all patients with intermediate to high
      risk probability MDCT pulmonary angiography is the most accurate test to diagnose
      PE and should be performed at the earliest. The combination of 2-dimensional ECHO
      and d-dimer can be used in patients with a high clinical suspicion of PE on pre
      test probability where MDCT pulmonary angiography is not possible.

PMID- 24023472
TI  - Assessment of voltage criteria for left ventricular hypertrophy in adult
      hypertensives in south-western Nigeria.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is a common pathophysiological
      consequence of hypertension. Various voltage (ECG) criteria exist for evaluation
      of LVH. This study assessed the performance of 4 commonly used ECG criteria in
      south-western Nigeria. MATERIALS AND METHODS: A cross-sectional descriptive study
      of adult hypertensive subjects. Participants were assessed for LVH using 4 ECG
      criteria: Sokolow-Lyon, Araoye code system, Cornell voltage, and Gubner
      Ungerleider criteria. Echocardiography was used to determine the left ventricular
      mass index for the participants, and a value greater than 125 g/m(2) was used as
      the cut-off point for LVH. The sensitivity, specificity, accuracy, positive and
      negative predictive values were determined for each of the ECG criteria. RESULTS:
      90 subjects (45 males, 45 females) participated in the study. The prevalence of
      LVH by echocardiography was 32.2%. The prevalence of LVH by voltage criteria
      were: 45.6%, 42.2%, 34.4%, 13.3% by Sokolow-Lyon, Araoye code system, Cornell,
      and Gubner-Ungerleider criteria, respectively. The sensitivity and specificity
      respectively of the ECG criteria were 58.62% and 60.66% (Sokolow-Lyon), 48.28%
      and 60.65% (Araoye code system), 51.72% and 73.77% (Cornell), and 13.79% and
      86.89% (Gubner-Ungerleider). CONCLUSION: Out of the 4 ECG criteria, Araoye code
      system, Cornell and Sokolow-Lyon criteria compared favorably well with
      echocardiography and may be used in the initial assessment of LVH in adult
      hypertensive subjects. However, a combination of any of the 3 criteria with
      Gubner-Ungerleider criterion will be more clinically useful.

PMID- 24023473
TI  - Coronary anatomy characteristics in patients with isolated right bundle branch
      block versus subjects with normal surface electrocardiogram.
AB  - INTRODUCTION AND OBJECTIVE: Isolated right bundle branch block is a common
      finding in the general population. It may be associated with variations in
      detailed coronary anatomy characteristics. The aim of this study was to
      investigate the coronary anatomy in patients with isolated right bundle branch
      block and to compare that with normal individuals. METHOD: In this case-control
      study we investigated the coronary anatomy by reviewing angiographic films in two
      groups of normal coronary artery patients: patients with right bundle branch
      block (RBBB) (n = 92) and those with normal electrocardiograms (n = 184).
      RESULTS: There was no significant difference between the two groups in terms of
      diminutive left anterior descending artery, dominancy, number of obtuse marginal
      artery, diagonal, acute marginal artery, the position of the first septal versus
      diagonal branch, presence of ramus artery, and size of left main artery. The
      number of septal branches was higher in the case group (p-value <0.001).
      Origination of the atrioventricular node artery from the right circulatory system
      was more common in both groups but cases showed more tendency to follow this
      pattern (p-value = 0.021). The frequency of the normal conus branch was higher in
      the cases versus controls (p-value = 0.009). CONCLUSIONS: Coronary anatomy
      characteristics are somewhat different in subjects with RBBB compared to normal
      individuals.

PMID- 24023474
TI  - A special case of Wellens' syndrome.
AB  - Wellens' syndrome is a pattern of electrocardiographic T-wave changes associated
      with critical stenosis of proximal left anterior descending artery (LAD). T-waves
      abnormalities were found in precordial leads, especially in V2-V3 during pain
      free periods, and ECG obtained during episodes of pain demonstrates upright T
      waves with possible elevated or isoelectric ST segments. Early recognition and
      appropriate intervention carries significant diagnostic and prognostic value. We
      reported a case of Wellens' syndrome with different etiology and prognosis.
      Although the ECG showed typical T-wave changes in V2-V5 leads, patient's coronary
      angiography revealed moderate stenosis in proximal LAD, and coronary artery spasm
      was suggested. Unlike the classic Wellens' syndrome, which needs aggressive
      coronary intervention, our patient fared well with conservative medical therapy
      (diltiazem and nitrates) and showed favorable prognosis. 

PMID- 24023475
TI  - Pasteurella multocida infective endocarditis in an immunocompetent patient
      complicated by rhabdomyolysis and permanent hearing loss.
AB  - Pasteurella multocida is an inhabitant of the oral cavity of a variety of
      livestock and domestic pet species, especially cats and dogs. The case reported
      illustrates a 60-year-old, immunocompetent female patient who presented with P.
      multocida sepsis and aortic valve endocarditis. This required surgical
      bioprosthetic aortic valve replacement. Investigation also found infection
      induced rhabdomyolysis and permanent hearing loss, both previously unassociated
      with P. multocida infection. 

PMID- 24023476
TI  - Reversible myocardial dysfunction following intraocular bevacizumab
      administration.
AB  - Heart failure has been reported as a rare side effect of bevacizumab, a
      chemotherapeutic agent, used in the treatment of breast cancer. However,
      reversible left ventricular systolic dysfunction with a pattern similar to stress
      induced cardiomyopathy has not been reported. The etiopathogenesis of stress
      induced cardiomyopathy is poorly understood. Given this uncertainty, we should
      always look out for other potential offenders causing similar presentation,
      rather than label all of them as "stress-induced". 

PMID- 24023477
TI  - Cardio-embolic stroke following remote blunt chest trauma.
AB  - A cardio-embolic stroke as a sequela of remote blunt chest trauma is a rare
      clinical presentation. Blunt chest trauma can cause various acute cardiac
      complications like arrhythmias, cardiac contusion etc. However, delayed
      consequences such as left ventricular thrombus resulting in thromboembolic
      phenomena are reported infrequently. A 30-year-old healthy man presented to an
      outside facility with transient neurological deficits. An MRI brain showed
      lesions suggestive of embolic etiology. A trans-thoracic echocardiogram (TTE)
      showed a 1.5 * 1.5 cm mass present in the left ventricular (LV) apex. Patient was
      transferred to our institution for cardiac surgery evaluation. On detailed
      questioning, he reported an incident of blunt chest trauma during a martial arts
      exhibition fight that took place 2 years back. Given this history, a cardiac
      catheterization was done, which showed 30% stenosis in mid-left anterior
      descending artery (LAD) without any other significant obstructive lesion. A trans
      esophageal echocardiogram (TEE) showed akinesis of the LV apex and confirmed TTE
      finding of a mass, consistent with an apical thrombus. Surgery was deferred and
      patient was started on anticoagulation. A cardiac MRI done 2 weeks later showed
      evidence of apical infarction in the LAD territory. LAD is the most commonly
      affected coronary vessel by blunt traumatic injuries, likely due to its
      vulnerable anatomical position on the anterior aspect of the heart. A variety of
      mechanisms including intimal tear, rupture and spasm have been implicated in the
      pathogenesis of myocardial infarction after blunt chest trauma. 

PMID- 24023478
TI  - Severe hypertension in elapid envenomation.
AB  - Snakebite is not an uncommon medical emergency in India; however, symptoms of
      autonomic dysfunction in snakebite are rare. The elapid snake envenomation is a
      frequent occurrence in India, and the krait bite is prevalent in the south Indian
      region. Here, we present three cases of snakebite with severe hypertension and
      requiring intravenous nitroglycerin (NTG). As the level of blood pressure (BP)
      decreased significantly following antisnake venom (ASV) injection in all three
      cases, it is likely that snake venom-induced dysautonomia might have contributed
      to severe hypertension in such patients. Clinical and therapeutic challenges of
      these cases are highlighted, so that practitioners coping with medical
      emergencies in resource-limited situations can consider snake (krait) bite in the
      differential diagnosis, and also manage effectively according to corroborative
      clinical evidences. 

PMID- 24023479
TI  - Unusual presentation of a culture-positive right atrial mass.
AB  - We report a patient with a mass in the right atrium which led to pulmonary
      embolism. Postoperatively the mass was identified as a tuberculoma and it was
      culture-positive for Mycobacterium tuberculosis. Patient responded to modified
      antitubercular treatment and discharged from hospital in satisfactory condition. 

PMID- 24023480
TI  - Implementing telestroke to reduce the burden of stroke in Louisiana.
AB  - Cardiovascular diseases (heart diseases and stroke) are the leading cause of
      death in the United States. People living in rural areas have disproportionately
      high mortality rates due to stroke mainly due to lack of specialty services.
      Timely intervention is a critical factor in determining the prognosis for acute
      stroke and thousands of lives can be saved by recognizing/treating a stroke
      patient within an hour. This paper deals with telestroke, a unique intervention
      implemented in Louisiana that incorporated latest technology to integrate with
      advanced clinical protocols in treating acute stroke. People living in remote and
      rural areas of Louisiana were greatly benefited from this initiative and several
      lives saved as a result of timely intervention. Expanding these initiatives to
      larger populations and other states will greatly reduce the stroke mortality. 

PMID- 24023481
TI  - A rare variant of single coronary artery presenting with angina.

PMID- 24023482
TI  - HLA class II associated with outcomes of hepatitis B and C infections.
AB  - Several factors influence the clinical course of hepatitis B virus (HBV) and
      hepatitis C virus (HCV) infection. The human leukocyte antigen (HLA) system, the
      major histocompatibility complex (MHC) in humans, has been considered one of the
      most important host factors with respect to outcomes. To date, conventional
      genotyping studies have shown that HLA class II loci are mainly associated with
      spontaneous clearance of HBV and HCV. However, the specific HLA locus associated
      with the outcomes of hepatitis virus infection remains unclear. A recent genome
      wide association study (GWAS) using a comprehensive approach for human genotyping
      demonstrated single nucleotide polymorphisms (SNPs) associated with the outcomes
      of hepatitis virus infection. Examination of large numbers of cohorts revealed
      that several SNPs in both HLA-DPA1 and HLA-DPB1 loci are associated with
      persistent HBV infection in Asian populations. To date, however, few studies have
      focused on HLA-DP because polymorphisms of HLA-DP haplotype do not vary greatly
      as compared with other loci of HLA. There are not enough studies to reveal the
      function of HLA-DP. GWAS additionally detected candidate SNPs within HLA loci
      associated with chronic HBV or HCV hepatitis, hepatic fibrosis, and the
      development of hepatocellular carcinoma. The results of one cohort were not
      always consistent with those of other cohorts. To solve several controversial
      issues, it is necessary to validate reported SNPs on HLA loci in global
      populations and to elucidate the HLA-allele-regulated molecular response to
      hepatitis virus infection. 

PMID- 24023484
TI  - Current status in the treatment options for esophageal achalasia.
AB  - Recent advances in the treatment of achalasia include the use of high-resolution
      manometry to predict the outcome of patients and the introduction of peroral
      endoscopic myotomy (POEM). The first multicenter randomized, controlled, 2-year
      follow-up study conducted by the European Achalasia Trial group indicated that
      laparoscopic Heller myotomy (LHM) was not superior to pneumatic dilations (PD).
      Publications on the long-term success of laparoscopic surgery continue to emerge.
      In addition, laparoscopic single-site surgery is applicable to advanced
      laparoscopic operations such as LHM and anterior fundoplication. The optimal
      treatment option is an ongoing matter of debate. In this review, we provide an
      update of the current progress in the treatment of esophageal achalasia. Unless
      new conclusive data prove otherwise, LHM is considered the most durable treatment
      for achalasia at the expense of increased reflux-associated complications.
      However, PD is the first choice for non-surgical treatment and is more cost
      effective. Repeated PD according to an "on-demand" strategy based on symptom
      recurrence can achieve long-term remission. Decision making should be based on
      clinical evidence that identifies a subcategory of patients who would benefit
      from specific treatment options. POEM has shown promise but its long-term
      efficacy and safety need to be assessed further. 

PMID- 24023485
TI  - Practice guidelines for ultrasound-guided percutaneous microwave ablation for
      hepatic malignancy.
AB  - Primary liver cancer and liver metastases are among the most frequent
      malignancies worldwide, with an increasing number of new cases and deaths every
      year. Traditional surgery is only suitable for a limited proportion of patients
      and imaging-guided percutaneous thermal ablation has achieved optimistic results
      for management of hepatic malignancy. This synopsis outlines the first clinical
      practice guidelines for ultrasound-guided percutaneous microwave ablation therapy
      for hepatic malignancy, which was created by a joint task force of the Society of
      Chinese Interventional Ultrasound. The guidelines aim at standardizing the
      microwave ablation procedure and therapeutic efficacy assessment, as well as
      proposing the criteria for the treatment candidates. 

PMID- 24023486
TI  - Epigenetics of hepatocellular carcinoma: role of microRNA.
AB  - Hepatocellular carcinoma (HCC) represents a major form of primary liver cancer in
      adults. MicroRNAs (miRs), small non-coding single-stranded RNAs of 19-24
      nucleotides in length, negatively regulate the expression of many target genes at
      the post-transcriptional and/or translational levels and play a critical role in
      the initiation and progression of HCC. In this review we have summarized the
      information of aberrantly expressed miRs in HCC, their mechanism of action and
      relationship to cancer. The recent advances in HCC research reveal that miRs
      regulate expression of various oncogenes and tumor suppressor genes, thereby
      contributing to the modulation of diverse biological processes including
      proliferation, apoptosis, epithelial to mesenchymal transition and metastasis.
      From a clinical viewpoint, polymorphisms within miR-binding sites are associated
      with the risk of HCC. Polymorphisms in miR related genes have been shown to
      correlate with survival or treatment outcome in patients. Furthermore, the review
      focuses on the potential role of miRs as novel biomarkers and their translational
      applications for diagnosis and therapy in HCC. With further insights into miR
      deregulation in HCC, it is expected that novel miR-based therapeutics will arise.
      Also, we orient the readers to other reviews that may provide better
      understanding of miR research in HCC. 

PMID- 24023487
TI  - HBV endemicity in Mexico is associated with HBV genotypes H and G.
AB  - Hepatitis B virus (HBV) genotypes have distinct genetic and geographic diversity
      and may be associated with specific clinical characteristics, progression,
      severity of disease and antiviral response. Herein, we provide an updated
      overview of the endemicity of HBV genotypes H and G in Mexico. HBV genotype H is
      predominant among the Mexican population, but not in Central America. Its
      geographic distribution is related to a typical endemicity among the Mexicans
      which is characterized by a low hepatitis B surface antigen seroprevalence,
      apparently due to a rapid resolution of the infection, low viral loads and a high
      prevalence of occult B infection. During chronic infections, genotype H is
      detected in mixtures with other HBV genotypes and associated with other co
      morbidities, such as obesity, alcoholism and co-infection with hepatitis C virus
      or human immunodeficiency virus. Hepatocellular carcinoma prevalence is low.
      Thus, antiviral therapy may differ significantly from the standard guidelines
      established worldwide. The high prevalence of HBV genotype G in the Americas,
      especially among the Mexican population, raises new questions regarding its
      geographic origin that will require further investigation. 

PMID- 24023483
TI  - What does irritable bowel syndrome share with non-alcoholic fatty liver disease?
AB  - Non-alcoholic fatty liver disease (NAFLD) and irritable bowel syndrome (IBS) are
      two very common diseases in the general population. To date, there are no studies
      that highlight a direct link between NAFLD and IBS, but some recent reports have
      found an interesting correlation between obesity and IBS. A systematic PubMed
      database search was conducted highlighting that common mechanisms are involved in
      many of the local and systemic manifestations of NAFLD, leading to an increased
      cardiovascular risk, and IBS, leading to microbial dysbiosis, impaired intestinal
      barrier and altered intestinal motility. It is not known when considering local
      and systemic inflammation/immune system activation, which one has greater
      importance in NAFLD and IBS pathogenesis. Also, the nervous system is implicated.
      In fact, inflammation participates in the development of mood disorders, such as
      anxiety and depression, characteristics of obesity and consequently of NAFLD and,
      on the other hand, in intestinal hypersensitivity and dysmotility. 

PMID- 24023488
TI  - Biliary phosphatidylcholine and lysophosphatidylcholine profiles in sclerosing
      cholangitis.
AB  - AIM: To analyze phospholipid profiles in intrahepatic bile from patients with
      primary sclerosing cholangitis (PSC) and secondary sclerosing cholangitis (SSC).
      METHODS: Intrahepatic bile specimens collected via endoscopic retrograde
      cholangiography from 41 patients were analyzed. Fourteen of these patients were
      diagnosed with PSC, 10 with SSC, 11 with choledocholithiasis or no identifiable
      biliary disease, and 6 with cholangiocellular carcinoma (CCC). Bile acid,
      cholesterol, protein, and bilirubin contents as well as pancreas lipase activity
      in bile were determined by biochemical methods. Phosphatidylcholine (PC) and
      lysophosphatidylcholine (LPC) species were quantified using nano-electrospray
      ionization tandem mass spectrometry. RESULTS: Bile from all the examined patient
      groups showed a remarkably similar PC and LPC species composition, with only
      minor statistical differences. Total biliary PC concentrations were highest in
      controls (8030 +/- 1843 MUmol/L) and lowest in patients with CCC (1969 +/- 981
      MUmol/L) (P = 0.005, controls vs SSC and CCC, respectively, P < 0.05). LPC
      contents in bile were overall low (4.2% +/- 1.8%). Biliary LPC/PC ratios and
      ratios of biliary PC to bilirubin, PC to cholesterol, PC to protein, and PC to
      bile acids showed no intergroup differences. CONCLUSION: PC and LPC profiles
      being similar in patients with or without sclerosing cholangitis, these
      phospholipids are likely not of major pathogenetic importance in this disease
      group.

PMID- 24023489
TI  - Extracorporeal continuous portal diversion plus temporal plasmapheresis for
      "small-for-size" syndrome.
AB  - AIM: To investigate the effect of plasmapheresis via the portal vein for "small
      for-size" syndrome (SFSS) aided by extracorporeal continuous portal diversion
      (ECPD). METHODS: Extensive or total hepatectomy in the pig is usually adopted as
      a postoperative liver failure (PLF) or SFSS model. In this study, animals which
      underwent 85%-90% hepatectomy were randomized into either the Systemic group (n =
      7) or the Portal group (n = 7). In the Systemic group, all pigs received temporal
      plasmapheresis (PP) via the extracorporeal catheter circuit (systemic to systemic
      circulation) from 24 to 30 h post-hepatectomy (PH); in the Portal group, all pigs
      received ECPD to divert partial portal vein flow (PVF) to the systemic
      circulation after hepatectomy, then converted to temporal PP from 24 to 30 h PH,
      and subsequently converted to ECPD again until 48 h PH. In the Portal group, the
      PVF was preserved at 3.0-3.3 times that of the baseline value, similar to that
      following 70% hepatectomy, which was regarded as the optimal PVF to the
      hypertrophic liver remnant. At 48 h PH, all pigs were re-opened and the portal
      vein pressure (PVP), PVF, and HAF (hepatic artery flow) were measured, and then
      diversion of the portal venous flow was terminated. After 1 h the PVP, PVF, and
      HAF were re-measured. The portal hemodynamic changes, liver injury, liver
      regeneration and bacterial/lipopolysaccharide (LPS) translocation were evaluated
      in the two groups. RESULTS: The PVP in the Portal group was significantly lower
      than that in the Systemic group during the time period from 2 to 49 h PH (P <
      0.05). Serum alanine aminotransferase (ALT), total bilirubin (TB) and ammonia
      were significantly reduced in the Portal group compared with the Systemic group
      from 24 to 48 h PH (P < 0.05). The Portal group may have attenuated sinusoidal
      endothelial injury and decreased the level of HA compared with the Systemic
      group. In the Systemic group, there was significant sinusoidal dilation, hydropic
      changes in hepatocytes and hemorrhage into the hepatic parenchyma, and the
      sinusoidal endothelial lining was partially destroyed and detached into the
      sinusoidal space. CD31 immunostaining revealed significant destruction of the
      endothelial lining. In the Portal group, there was no intraparenchymal hemorrhage
      and the sinusoidal endothelial cells and hepatocytes were well preserved. CD31
      immunostaining was mild which indicated less destruction of the endothelial
      lining. HA was significantly decreased in the Portal group compared with the
      Systemic group from 2 to 48 h PH. The rate of liver remnant regeneration was
      elevated, while apoptosis was attenuated in the Portal group compared with the
      Systemic group. Thymidine kinase activity was much higher in the Portal group
      than in the Systemic group at 48 h PH. The PCNA index was significantly increased
      and the apoptotic index was significantly decreased in the Portal group compared
      with the Systemic group. Bacterial translocation and endotoxin, as well as the
      inflammatory response, were significantly attenuated in the Portal group compared
      with the Systemic group. LPS, tumor necrosis factor-alpha and interleukin-6
      levels were all significantly decreased in the Portal group compared with the
      Systemic group from 24 to 48 h PH, while bacterial DNA level was significantly
      decreased from 2 to 48 h PH. CONCLUSION: PP plus ECPD via the portal vein can
      attenuate toxic load and hyperperfusion injury, and should be undertaken instead
      of PP via the systemic circulation in SFSS or PLF.

PMID- 24023490
TI  - Xiaotan Tongfu granules contribute to the prevention of stress ulcers.
AB  - AIM: To investigate the efficacy and potential mechanism of Xiaotan Tongfu
      granules (XTTF) in stress ulcers. METHODS: One hundred sixty rats were randomly
      divided into 4 groups (n = 10) as follows: the model group (MP group), the
      control group (CP group), the ranitidine group (RP group) and the XTTF granule
      group (XP group). Rats in the MP group received no drugs, rats in the CP group
      received 0.2 mL of a 0.9% sodium chloride solution via oral gavage, and rats in
      the RP and XP groups received the same volume of ranitidine (50 mg/kg) or XTTF
      granule (4.9 g/kg). The cold-restraint stress model was applied to induce stress
      ulcers after 7 consecutive days of drug administration. Afterwards, rats were
      sacrificed at 0, 3, 6 and 24 h. Gastric pH was measured by a precise pH meter;
      gastric emptying rate (GER) was measured by using a methylcellulose test meal;
      myeloperoxidase activity (MPO), macrophage migration inhibitory factor (MIF),
      proliferating cell nuclear antigen (PCNA), and heat shock protein 70 (HSP70) were
      measured by immunohistochemical staining; and mucosal cell apoptosis was measured
      by transferase dUTP nick end labeling. RESULTS: In the cold-restraint stress
      model, the development of stress ulcers peaked at 3 h and basically regressed
      after 24 h. Gastric lesions were significantly different in the RP and XP groups
      at each time point. Interestingly, although this index was much lower in the RP
      group than in the XP group immediately following stress induction (7.00 +/- 1.10
      vs 10.00 +/- 1.79, P < 0.05. Concerning gastric pH, between the RP and XP groups,
      we detected a statistically significant difference immediately after stress
      induction (0 h: 4.56 +/- 0.47 vs 3.34 +/- 0.28, P < 0.05) but not at any of the
      subsequent time points. For GER, compared to the RP group, GER was remarkably
      elevated in the XP group because a statistically significant difference was
      detected (3 h: 46.84 +/- 2.70 vs 61.16 +/- 5.12, P < 0.05; 6 h: 60.96 +/- 6.71 vs
      73.41 +/- 6.16, P < 0.05; 24 h: 77.47 +/- 3.17 vs 91.31 +/- 4.34, P < 0.05). With
      respect to MPO and MIF, comparisons between the RP and XP groups revealed
      statistically significant differences at 3 h (MPO: 18.94 +/- 1.20 vs 13.51 +/-
      0.89, P < 0.05; MIF: 150.67 +/- 9.85 vs 122.17 +/- 5.67, P < 0.05) and 6 h (MPO:
      13.22 +/- 1.54 vs 8.83 +/- 0.65, P < 0.05; MIF: 135.50 +/- 9.46 vs 109.83 +/-
      6.40, P < 0.05). With regard to HSP70, HSP70 expression was significantly
      increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups.
      In addition, comparing the RP and XP groups also showed statistically significant
      differences at 3 and 6 h. The expression of PCNA was higher in the RP and XP
      groups 3 h after stress induction. Between these two groups, small but
      statistically significant differences were observed at all of the time points (3
      h: 69.50 +/- 21.52 vs 79.33 +/- 15.68, P < 0.05; 6 h: 107.83 +/- 4.40 vs 121.33
      +/- 5.71, P < 0.05; 24 h: 125.33 +/- 5.65 vs 128.50 +/- 14.49, P < 0.05) except 0
      h. With regard to apoptosis, the apoptotic activity in the RP and XP groups was
      significantly different from that in the MP and CP groups. The XP group exhibited
      a higher inhibition of cell apoptosis than the RP group at 3 h (232.58 +/- 24.51
      vs 174.46 +/- 10.35, P < 0.05) and 6 h (164.74 +/- 18.31 vs 117.71 +/- 12.08, P <
      0.05). CONCLUSION: The Xiaotan Tongfu granule was demonstrated to be similar to
      ranitidine in preventing stress ulcers. It exhibited multiple underlying
      mechanisms and deserves further study.

PMID- 24023491
TI  - Propofol induces apoptosis and increases gemcitabine sensitivity in pancreatic
      cancer cells in vitro by inhibition of nuclear factor-kappaB activity.
AB  - AIM: To investigate the effect of propofol on human pancreatic cells and the
      molecular mechanism of propofol action. METHODS: We used the human pancreatic
      cancer cell line MIAPaCa-2 for in vitro studies measuring growth inhibition and
      degree of apoptotic cell death induced by propofol alone, gemcitabine alone, or
      propofol followed by gemcitabine. All experiments were conducted in triplicate
      and carried out on three or more separate occasions. Data were means of the three
      or more independent experiments +/- SE. Statistically significant differences
      were determined by two-tailed unpaired Student's t test and defined as P < 0.05.
      RESULTS: Pretreatment of cells with propofol for 24 h followed by gemcitabine
      resulted in 24%-75% growth inhibition compared with 6%-18% when gemcitabine was
      used alone. Overall growth inhibition was directly correlated with apoptotic cell
      death. We also showed that propofol potentiated gemcitabine-induced killing by
      downregulation of nuclear factor-kappaB (NF-kappaB). In contrast, NF-kappaB was
      upregulated when pancreatic cancer cells were exposed to gemcitabine alone,
      suggesting a potential mechanism of acquired chemoresistance. CONCLUSION:
      Inactivation of the NF-kappaB signaling pathway by propofol might abrogate
      gemcitabine-induced activation of NF-kappaB, resulting in chemosensitization of
      pancreatic tumors to gemcitabine.

PMID- 24023492
TI  - Bisacodyl plus split 2-L polyethylene glycol-citrate-simethicone improves quality
      of bowel preparation before screening colonoscopy.
AB  - AIM: To compare the bowel cleansing efficacy, tolerability and acceptability of
      split 2-L polyethylene glycol (PEG)-citrate-simethicone (PEG-CS) plus bisacodyl
      (BIS) vs 4-L PEG for fecal occult blood test-positive screening colonoscopy.
      METHODS: This was a randomised, observer-blind comparative study. Two hundred and
      sixty-four subjects underwent screening colonoscopy (mean age 62.5 +/- 7.4 years,
      male 61.7%). The primary objective of the study was to compare the bowel
      cleansing efficacy of the two preparations. INTERVENTIONS: BIS plus PEG-CS: 3
      tablets of 5-mg BIS at 16:00, PEG-CS 1-L at 19:00 and 1-L at 7:00, 4-L PEG: 3-L
      at 17:00, and 1-L at 7:00. Colonoscopy was carried out after 11:00, at least 3 h
      after the completion of bowel preparation. Bowel cleansing was evaluated using
      the Harefield Cleansing Scale. RESULTS: Bowel preparation was successful for
      92.8% of subjects in the PEG-CS group and for 92.1% of subjects in the 4-L PEG
      (RR = 1.01; 95%CI: 0.94-1.08). BIS + PEG-CS was better tolerated than 4-L PEG. A
      greater rate of patients in the BIS + PEG-CS group had no difficulty and/or were
      willing to repeat the same preparation compared to split-dose 4-L PEG group.
      Subjects in the BIS + PEG-CS group rated the prep as good or satisfactory in
      90.6% as compared to 77% in the 4-L PEG (P = 0.003). Subjects receiving BIS + PEG
      CS stated they fully adhered to instructions drinking all the 2-L solution in
      97.1% compared with 87.3% in the 4-L PEG (P = 0.003). CONCLUSION: BIS plus split
      2-L PEG-CS was as effective as but better tolerated and accepted than split 4-L
      PEG for screening colonoscopy. This new procedure may increase the positive
      attitude and participation to colorectal cancer screening colonoscopy.

PMID- 24023493
TI  - Fucoidan enhances intestinal barrier function by upregulating the expression of
      claudin-1.
AB  - AIM: To evaluate the protective effects of fucoidan on oxidative stress-induced
      barrier disruption in human intestinal epithelial cells. METHODS: In Caco-2 cell
      monolayer models, the disruption of barrier function by oxidative stress is
      mediated by H2O2. The integrity of polarized Caco-2 cell monolayers was
      determined by measuring the transepithelial resistance (TER) and permeability was
      estimated by measuring the paracellular transport of FITC-labeled 4-kDa dextran
      (FD4). The protective effects of fucoidan on epithelial barrier functions on
      polarized Caco-2 cell monolayers were evaluated by TER and FD4 flux. The
      expression of tight junction (TJ) proteins was assessed using reverse
      transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining.
      RESULTS: Without H2O2 treatment, fucoidan significantly increased the TER
      compared to control (P < 0.05), indicating a direct enhancement of intestinal
      epithelial barrier function. Next, H2O2 disrupted the epithelial barrier function
      in a time-dependent manner. Fucoidan prevented the H2O2-induced destruction in a
      dose-dependent manner. Fucoidan significantly decreased H2O2-induced FD4 flux (P
      < 0.01), indicating the prevention of disruption in paracellular permeability. RT
      PCR showed that Caco-2 cells endogenously expressed claudin-1 and -2, and
      occludin and that H2O2 reduced the mRNA expression of these TJ proteins.
      Treatment with fucoidan attenuated the reduction in the expressions of claudin-1
      and claudin-2 but not occludin. Immunofluorescence staining revealed that the
      expression of claudin-1 was intact and high on the cell surface. H2O2 disrupted
      the integrity of claudin-1. Treatment with fucoidan dramatically attenuated the
      expression of claudin-1. CONCLUSION: Fucoidan enhanced intestinal epithelial
      barrier function by upregulating the expression of claudin-1. Thus, fucoidan may
      be an appropriate therapy for the treatment of inflammatory bowel diseases.

PMID- 24023494
TI  - Antibiotics resistance rate of Helicobacter pylori in Bhutan.
AB  - AIM: To survey the antibiotic resistance pattern of Helicobacter pylori (H.
      pylori) strains isolated from Bhutanese population. METHODS: We isolated 111 H.
      pylori strains from the gastric mucosa of H. pylori-infected patients in Bhutan
      in 2010. The Epsilometer test was used to determine the minimum inhibitory
      concentrations (MICs) of amoxicillin (AMX), clarithromycin (CLR), metronidazole
      (MNZ), levofloxacin (LVX), ciprofloxacin (CIP), and tetracycline (TET). RESULTS:
      Nineteen of the isolated H. pylori strains were susceptible to all antibiotics
      tested. The isolated strains showed the highest rate of antibiotic resistance to
      MNZ (92/111, 82.9%). Among the 92 MNZ-resistant strains, 74 strains (80.4%)
      showed high-level resistance (MIC >= 256 MUg/mL). Three strains were resistance
      to LVX (2.7%). These strains were also resistance to CIP. None of the strains
      showed resistance to CLR, AMX and TET. CONCLUSION: CLR-based triple therapy is a
      more effective treatment approach over MNZ-based triple therapy for H. pylori
      infection in Bhutan.

PMID- 24023495
TI  - Self-expandable metallic stent placement plus laparoscopy for acute malignant
      colorectal obstruction.
AB  - AIM: To investigate the clinical advantages of the stent-laparoscopy approach to
      treat colorectal cancer (CRC) patients with acute colorectal obstruction (ACO).
      METHODS: From April 2008 to April 2012, surgery-related parameters,
      complications, overall survival (OS), and disease-free survival (DFS) of 74
      consecutive patients with left-sided CRC presented with ACO who underwent self
      expandable metallic stent (SEMS) placement followed by one-stage open (n = 58) or
      laparoscopic resection (n = 16) were evaluated retrospectively. The stent
      laparoscopy group was also compared with a control group of 96 CRC patients who
      underwent regular laparoscopy without ACO between January 2010 and December 2011
      to explore whether SEMS placement influenced the laparoscopic procedure or
      reduced long-term survival by influencing CRC oncological characteristics.
      RESULTS: The characteristics of patients among these groups were comparable. The
      rate of conversion to open surgery was 12.5% in the stent-laparoscopy group.
      Bowel function recovery and postoperative hospital stay were significantly
      shorter (3.3 +/- 0.9 d vs 4.2 +/- 1.5 d and 6.7 +/- 1.1 d vs 9.5 +/- 6.7 d, P =
      0.016 and P = 0.005), and surgical time was significantly longer (152.1 +/- 44.4
      min vs 127.4 +/- 38.4 min, P = 0.045) in the stent-laparoscopy group than in the
      stent-open group. Surgery-related complications and the rate of admission to the
      intensive care unit were lower in the stent-laparoscopy group. There were no
      significant differences in the interval between stenting and surgery,
      intraoperative blood loss, OS, and DFS between the two stent groups. Compared
      with those in the stent-laparoscopy group, all surgery-related parameters,
      complications, OS, and DFS in the control group were comparable. CONCLUSION: The
      stent-laparoscopy approach is a feasible, rapid, and minimally invasive option
      for patients with ACO caused by left-sided CRC and can achieve a favorable long
      term prognosis.

PMID- 24023496
TI  - Diffusion-weighted magnetic resonance imaging for predicting the response of
      rectal cancer to neoadjuvant concurrent chemoradiation.
AB  - AIM: To evaluate the clinical value of diffusion-weighted magnetic resonance
      imaging (DW-MRI) in predicting the response of rectal cancer to neoadjuvant
      chemoradiation. METHODS: This prospective study was approved by our institutional
      review board, and informed consent was obtained from each patient. Fifteen
      patients (median age 56 years) with locally advanced rectal cancer were treated
      in our hospital from June 2006 to December 2007. All patients were stage IIIB-C
      according to the results of MRI and endorectal ultrasound examinations. All
      patients underwent pelvic irradiation with 45 Gy/25 fx per 35 days. The
      concurrent chemotherapy regimen consisted of capecitabine 625 mg/m2, bid (Monday
      Friday), and oxaliplatin 50 mg/m2, weekly. The patients underwent surgery 5-8 wk
      after the completion of neoadjuvant therapy. T downstaging was defined as the
      downstaging of the tumor from cT3 to ypT0-2 or from cT4 to ypT0-3. Good
      regression was defined as TRG 3-4, and poor regression was defined as TRG 0-2.
      Diffusion-weighted magnetic resonance images were obtained prior to and weekly
      during the course of neoadjuvant chemoradiation, and the apparent diffusion
      coefficient (ADC) values were calculated from the acquired tumor images. RESULTS:
      Comparison with the mean pretreatment tumor ADC revealed an increase in the mean
      tumor ADC during the course of neoadjuvant chemoradiation, especially at the
      2(nd) week (P = 0.004). We found a strong negative correlation between the mean
      pretreatment tumor ADC and tumor regression after neoadjuvant chemoradiation (P =
      0.021). In the T downstage and tumor regression groups, we found a significant
      increase in the mean ADC at the 2(nd) week of neoadjuvant therapy (P = 0.011;
      0.004). CONCLUSION: DW-MRI might be a valuable clinical tool to help predict or
      assess the response of rectal cancer to neoadjuvant chemoradiation at an early
      timepoint.

PMID- 24023497
TI  - Dual-sided composite mesh repair of hiatal hernia: our experience and a review of
      the Chinese literature.
AB  - AIM: To summarize our experience in the application of Crurasoft(r) for
      antireflux surgery and hiatal hernia (HH) repair and to introduce the work of
      Chinese doctors on this topic. METHODS: Twenty-one patients underwent HH repair
      with Crurasoft(r) reinforcement. Gastroesophageal reflux disease (GERD) and HH
      related symptoms including heartburn, regurgitation, chest pain, dysphagia, and
      abdominal pain were evaluated preoperatively and 6 mo postoperatively. A patient
      survey was conducted by phone by one of the authors. Patients were asked about
      "recurrent reflux or heartburn" and "dysphagia". An internet-based Chinese
      literature search in this field was also performed. Data extracted from each
      study included: number of patients treated, hernia size, hiatorrhaphy, antireflux
      surgery, follow-up period, recurrence rate, and complications (especially
      dysphagia). RESULTS: There were 8 type I, 10 type II and 3 type III HHs in this
      group. Mean operative time was 119.29 min (range 80-175 min). Intraoperatively,
      length and width of the hiatal orifice were measured, (4.33 +/- 0.84 and 2.85 +/-
      0.85 cm, respectively). Thirteen and eight Nissen and Toupet fundoplications were
      performed, respectively. The intraoperative complication rate was 9.52%. Despite
      dysphagia, GERD-related symptoms improved significantly compared with those
      before surgery. The recurrence rate was 0% during the 6-mo follow-up period, and
      long-term follow-up disclosed a recurrence rate of 4.76% with a mean period of
      16.28 mo. Eight patients developed new-onset dysphagia. The Chinese literature
      review identified 12 papers with 213 patients. The overall recurrence rate was
      1.88%. There was no esophageal erosion and the rate of dysphagia ranged from 0%
      to 24%. CONCLUSION: The use of Crurasoft(r) mesh for HH repair results in
      satisfactory symptom control with a low recurrence rate. Postoperative dysphagia
      continues to be an issue, and requires more research to reduce its incidence.

PMID- 24023498
TI  - Proposal of new classification for postoperative patients with hepatocellular
      carcinoma based on tumor growth characteristics.
AB  - AIM: To propose an appropriate staging system for hepatocellular carcinoma (HCC)
      classification. METHODS: Here, 288 in-patients with HCC were studied and divided
      into three groups: those with expansive growth, invasive growth (including
      satellite nodules, nodule fusions and direct tumor invasion of adjacent organs),
      or disseminative growth (including vascular involvement, regional lymph node
      metastasis and distant metastasis). A survival analysis was performed using a
      Kaplan-Meier analysis, and prognostic factors for overall survival were
      determined by the Cox proportional hazards regression model. RESULTS: The overall
      survival (OS) of patients with invasive tumor growth was shorter than that of
      patients with expansive tumor growth (27.796 +/- 3.730 and 57.398 +/- 4.873 mo,
      respectively, P < 0.001). No significant difference in survival was observed
      between patients with vascular involvement and patients with regional lymph node
      metastasis (21.667 +/- 4.773 and 14.619 +/- 2.456 mo, respectively, P = 0.801).
      The OS of patients with distant metastasis (6.417 +/- 1.395 mo) was shorter than
      that of the other groups (P < 0.001). No significant difference in survival was
      observed between patients with expansive tumor growth and vascular and/or
      regional lymph node involvement and patients with invasive tumor growth and no
      vascular and/or lymph node involvement (25.762 +/- 7.024, 21.200 +/- 7.794 and
      39.533 +/- 5.840 mo, respectively; P = 0.871, 0.307 and 0.563, respectively).
      CONCLUSION: These data led to the proposal of a new staging system: the Expansive
      Invasive-Disseminative growth staging classification.

PMID- 24023499
TI  - Impact of intraoperative blood loss on survival after curative resection for
      gastric cancer.
AB  - AIM: To elucidate the potential impact of intraoperative blood loss (IBL) on long
      term survival of gastric cancer patients after curative surgery. METHODS: A total
      of 845 stage I-III gastric cancer patients who underwent curative gastrectomy
      between January 2003 and December 2007 in our center were enrolled in this study.
      Patients were divided into 3 groups according to the amount of IBL: group 1 (<
      200 mL), group 2 (200-400 mL) and group 3 (> 400 mL). Clinicopathological
      features were compared among the three groups and potential prognostic factors
      were analyzed. The Log-rank test was used to assess statistical differences
      between the groups. Independent prognostic factors were identified by the Cox
      proportional hazards regression model. Stratified analysis was used to
      investigate the impact of IBL on survival in each stage. Cancer-specific survival
      was also compared among the three groups by excluding deaths due to reasons other
      than gastric cancer. Finally, we explored the possible factors associated with
      IBL and identified the independent risk factors for IBL >= 200 mL. RESULTS:
      Overall survival was significantly influenced by the amount of IBL. The 5-year
      overall survival rates were 51.2%, 39.4% and 23.4% for IBL less than 200 mL, 200
      to 400 mL and more than 400 mL, respectively (< 200 mL vs 200-400 mL, P < 0.001;
      200-400 mL vs > 400 mL, P = 0.003). Age, tumor size, Borrmann type, extranodal
      metastasis, tumour-node-metastasis (TNM) stage, chemotherapy, extent of
      lymphadenectomy, IBL and postoperative complications were found to be independent
      prognostic factors in multivariable analysis. Following stratified analysis,
      patients staged TNM I-II and those with IBL less than 200 mL tended to have
      better survival than those with IBL not less than 200 mL, while patients staged
      TNM III, whose IBL was less than 400 mL had better survival. Tumor location,
      tumor size, TNM stage, type of gastrectomy, combined organ resection, extent of
      lymphadenectomy and year of surgery were found to be factors associated with the
      amount of IBL, while tumor location, type of gastrectomy, combined organ
      resection and year of surgery were independently associated with IBL >= 200 mL.
      CONCLUSION: IBL is an independent prognostic factor for gastric cancer after
      curative resection. Reducing IBL can improve the long-term outcome of gastric
      cancer patients following curative gastrectomy.

PMID- 24023500
TI  - Effects of extended lymphadenectomy and postoperative chemotherapy on node
      negative gastric cancer.
AB  - AIM: To investigate the effects of extended lymphadenectomy and postoperative
      chemotherapy on gastric cancer without lymph node metastasis. METHODS: Clinical
      data of 311 node-negative gastric cancer patients who underwent potentially
      curative gastrectomy with more than 15 lymph nodes resected, from January 2002 to
      December 2006, were analyzed retrospectively. Patients with pT4 stage or distant
      metastasis were excluded. We analyzed the relationship between the D2
      lymphadenectomy and the 5-year survival rate among different subgroups stratified
      by clinical features, such as age, tumor size, tumor location and depth of
      invasion. At the same time, the relationship between postoperative chemotherapy
      and the 5-year survival rate among different subgroups were also analyzed.
      RESULTS: The overall 5-year survival rate of the entire cohort was 63.7%. The 5
      year survival rate was poor in those patients who were: (1) more than 65 years
      old; (2) with tumor size larger than 4 cm; (3) with tumor located in the upper
      portion of the stomach; and (4) with pT3 tumor. The survival rate was improved
      significantly by extended lymphadenectomy only in patients with pT3 tumor (P =
      0.019), but not in other subgroups. Moreover, there was no significant difference
      in survival rate between patients with and without postoperative chemotherapy
      among all of the subgroups (P > 0.05). CONCLUSION: For gastric cancer patients
      without lymph node metastasis, extended lymphadenectomy could improve the
      survival rate of those who have pT3-stage tumor. However, there was no evidence
      of a survival benefit from postoperative chemotherapy alone.

PMID- 24023501
TI  - Hypermethylation of TGF-beta1 gene promoter in gastric cancer.
AB  - AIM: To examine transforming growth factor-beta1 (TGF-beta1) promoter methylation
      in gastric cancer and to determine if Helicobacter pylori (H. pylori) or
      interleukin (IL)-1beta could induce TGF-beta1 hypermethylation in vitro. METHODS:
      We examined the frequency and extent of TGF-beta1 promoter methylation using
      methylation-specific PCR in the gastric tissues from 47 gastric cancer patients
      and 39 non-gastric cancer subjects. H. pylori infection was confirmed by a
      positive result from either a serological test, histological analysis or C13 urea
      breath test. GES-1 and MKN-45 cells co-cultured with H. pylori or treated with IL
      1beta for 12, 24 and 48 h in vitro tested the effects of H. pylori or IL-1beta on
      TGF-beta1. RESULTS: Twenty-four/forty-seven (51%) cases of gastric cancer (GC)
      tissues showed TGF-beta1 promoter methylation, 15/47 (31.9%) cases of matched non
      cancerous gastric mucosa tissues from the GC patients, and 11/39 (28%) case of
      the normal gastric mucosa tissues from non-GC subjects showed TGF-beta1 promoter
      methylation (51% vs 28%, P < 0.05). Significantly higher levels of methylation of
      TGF-beta1 were found in the tumor tissues than in non-tumor tissues from GC
      patients (0.24 +/- 0.06 vs 0.17 +/- 0.04, P < 0.05) and normal gastric tissues
      from non-GC subjects (0.24 +/- 0.06 vs 0.15 +/- 0.03, P < 0.05). TGF-beta1
      methylation was found in 48.3% of H. pylori-positive gastric mucosal tissues
      whereas only 23.1% of H. pylori-negative gastric mucosal tissues showed TGF-beta1
      methylation (48.3% vs 23.1%, P < 0.05). IL-1beta appeared to induce a dose
      dependent methylation of TGF-beta1 and the strongest methylation was observed in
      GES-1 cells treated with 2.5 ng/mL of IL-1beta for 48 h. Further studies showed
      that pre-treatment of GES-1 cells with 20 ng/mL IL-1RA for 1 h could partially
      abolish the effect of IL-1beta on TGF-beta1 methylation. Infection of GES-1 cells
      by H. pylori was not found to induce significant TGF-beta1 promoter methylation.
      CONCLUSION: Our data revealed that TGF-beta1 promoter is methylated in GC
      patients. IL-1beta may be an important mediator for H. pylori induced gene
      methylation during GC development.

PMID- 24023502
TI  - Palliative treatment for incurable malignant colorectal obstructions: a meta
      analysis.
AB  - AIM: To perform a meta-analysis of palliative stent placement vs palliative
      surgical decompression for management of incurable malignant colorectal
      obstructions. METHODS: The databases of Medline, Web of Science, Embase, and the
      Cochrane Central Register of Controlled Trials were searched from their inception
      to July 2012 for studies (prospective, retrospective, randomized controlled
      trials, and case-control trials) designed as comparative analyses of patients
      with incurable malignant colorectal obstructions treated by self-expanding
      metallic stents (SEMS) or palliative surgery. No language restrictions were
      imposed. The main outcome measures were hospital stay, intensive care unit
      admission, clinical success rate, 30-d mortality, stoma formation, complications,
      and overall survival time. The data extraction was conducted by two investigators
      working independently and using a standardized form. The Mantel-Haenszel chi2
      method was used to estimate the pooled risk ratios with 95%CI under a fixed
      effects model; when statistical heterogeneity existed in the pooled data (as
      evaluated by Q test and I2 statistics, where P < 0.10 and I2 < 25% indicated
      heterogeneity), a random-effects model was used. RESULTS: Thirteen relevant
      articles, representing 837 patients (SEMS group, n = 404; surgery group, n =
      433), were selected for analysis. Compared to the surgery group, the SEMS group
      showed lower clinical success (99.8% vs 93.1%, P = 0.0009) but shorter durations
      of hospital stay (18.84 d vs 9.55 d, P < 0.00001) and time to initiation of
      chemotherapy (33.36 d vs 15.53 d, P < 0.00001), and lower rate of stoma formation
      (54.0% vs 12.7%, P < 0.00001). Additionally, the SEMS group experienced a
      significantly lower rate of 30-d mortality (4.2% vs 10.5%, P = 0.01). Stent
      related complications were not uncommon and included perforation (10.1%),
      migration (9.2%), and occlusion (18.3%). Surgery-related complications were
      slightly less common and included wound infection (5.0%) and anastomotic leak
      (4.7%). The rate of total complications was similar between these two groups
      (SEMS: 34.0% vs surgery: 38.1%, P = 0.60), but the surgery-related complications
      occurred earlier than stent-related complications (rate of early complications:
      33.7% vs 13.7%, P = 0.03; rate of late complications: 32.3% vs 12.7%, P <
      0.0001). The overall survival time of SEMS- and surgery-treated patients was not
      significantly different (7.64 mo vs 7.88 mo). CONCLUSION: SEMS is less effective
      than surgery for palliation of incurable malignant colorectal obstructions, but
      is associated with a shorter time to chemotherapy and lower 30-d mortality.

PMID- 24023503
TI  - Lactic acidosis during telbivudine treatment for HBV: a case report and
      literature review.
AB  - All oral nucleoside analogues against hepatitis B virus, with an exception of
      telbivudine, have been reported causing lactic acidosis (LA). Here we report the
      first case of chronic hepatitis B developing severe refractory LA during
      telbivudine monotherapy. A 36-year-old man of Chinese origin received telbivudine
      antiviral treatment for chronic hepatitis B. After 11 mo of therapy, he developed
      anorexia, nausea, and vomiting with mild muscle weakness. The patient was found
      with elevated serum creatine phosphokinase up to 3683 U/L (upper limit of normal
      170 U/L) and marked LA. LA did not resolve immediately following discontinuation
      of telbivudine. His condition began to improve after hemodialysis treatment for
      16 times and usage of glucocorticosteroid. The patient fully recovered after 16
      wk of treatment. This is the first documented case with severe LA caused by
      telbivudine monotherapy. Besides serum creatine phosphokinase, blood lactate
      level should also be closely monitored in patients receiving telbivudine. 

PMID- 24023504
TI  - Selective endoscopic ligation for treatment of upper gastrointestinal protuberant
      lesions.
AB  - This study explored the clinical value of endoscopic ligation for the treatment
      of upper gastrointestinal (GI) protuberant lesions in children. According to the
      appearance and size of lesions, we used different ligation techniques for the
      treatment of the lesions. Endoscopic ultrasonography was used for preliminary
      characterization of the lesions. One case diagnosed with Peutz-Jeghers syndrome
      was successfully treated by a detachable snare. Two cases with semi-pedunculated
      or broad-base lesions originating from the submucosal layer of the upper GI were
      treated with endoscopic variceal ligation; endoscopic examination showed that one
      case had complete healing 11 wk after ligation, while an ulcer scar was observed
      at the ligation site after 6 wk in the other case. All lesions were successfully
      ligated at the first attempt. No significant complications occurred either during
      or after the procedure. Selective endoscopic ligation of upper GI lesions is an
      effective and safe treatment for upper GI protuberant lesions in children. 

PMID- 24023505
TI  - Gallstone ileus: case report and literature review.
AB  - Gallstone ileus (GI) is characterized by occlusion of the intestinal lumen as a
      result of one or more gallstones. GI is a rare complication of gallstones that
      occurs in 1%-4% of all cases of bowel obstruction. The mortality associated with
      GI ranges between 12% and 27%. Classical findings on plain abdominal radiography
      include: (1) pneumobilia; (2) intestinal obstruction; (3) an aberrantly located
      gallstone; and (4) change of location of a previously observed stone. The optimal
      management of acute GI is controversial and can be: (1) enterotomy with stone
      extraction alone; (2) enterotomy, stone extraction, cholecystectomy and fistula
      closure; (3) bowel resection alone; and (4) bowel resection with fistula closure.
      We describe a case to highlight some of the pertinent issues involved in GI
      management, and propose a scheme to minimize recurrent disease and postoperative
      complications. We conclude that GI is a rare condition affecting mainly the older
      population with a female predominance. The advent of computed tomography and
      magnetic resonance imaging has made it easier to diagnose GI. Enterotomy with
      stone extraction alone remains the most common surgical method because of its low
      incidence of complications. 

PMID- 24023506
TI  - Photodynamic therapy for high-grade dysplasia of bile duct via a choledochoscope.
AB  - When a distal common bile duct neoplasm is at the stage of carcinoma in situ or
      high-grade dysplasia, it is difficult for the surgeon to decide whether to
      perform pancreaticoduodenectomy. Here we describe a patient with a progressive
      dysplastic lesion in the common bile duct, which developed from moderate-high to
      high-grade dysplasia in approximately 2 mo. The patient refused major surgery.
      Therefore, endoscopic-assisted photodynamic therapy was performed. The result at
      follow-up using a trans-T-tube choledochoscope showed that the lesion was
      completely necrotic. This report is the first to describe the successful
      treatment of high-grade dysplasia of the distal bile duct using photodynamic
      therapy via a choledochoscope. 

PMID- 24023508
TI  - Analysis of protein thermostability enhancing factors in industrially important
      thermus bacteria species.
AB  - Elucidation of evolutionary factors that enhance protein thermostability is a
      critical problem and was the focus of this work on Thermus species. Pairs of
      orthologous sequences of T. scotoductus SA-01 and T. thermophilus HB27, with the
      largest negative minimum folding energy (MFE) as predicted by the UNAFold
      algorithm, were statistically analyzed. Favored substitutions of amino acids
      residues and their properties were determined. Substitutions were analyzed in
      modeled protein structures to determine their locations and contribution to
      energy differences using PyMOL and FoldX programs respectively. Dominant trends
      in amino acid substitutions consistent with differences in thermostability
      between orthologous sequences were observed. T. thermophilus thermophilic
      proteins showed an increase in non-polar, tiny, and charged amino acids. An
      abundance of alanine substituted by serine and threonine, as well as arginine
      substituted by glutamine and lysine was observed in T. thermophilus HB27.
      Structural comparison showed that stabilizing mutations occurred on surfaces and
      loops in protein structures. 

PMID- 24023507
TI  - HPV infection: immunological aspects and their utility in future therapy.
AB  - High prevalence and mortality rates of cervical cancer create an imperative need
      to clarify the uniqueness of HPV (Human Papillomavirus) infection, which serves
      as the key causative factor in cervical malignancies. Understanding the
      immunological details and the microenvironment of the infection can be a useful
      tool for the development of novel therapeutic interventions. Chronic infection
      and progression to carcinogenesis are sustained by immortalization potential of
      HPV, evasion techniques, and alterations in the microenvironment of the lesion.
      Inside the lesion, Toll-like receptors expression becomes irregular; Langerhans
      cells fail to present the antigens efficiently, tumor-associated macrophages
      aggregate resulting in an unsuccessful immune response by the host. HPV products
      also downregulate the expression of microenvironment components which are
      necessary for natural-killer cells response and antigen presentation to cytotoxic
      cells. Additionally HPV promotes T-helper cell 2 (Th2) and T-regulatory cell
      phenotypes and reduces Th1 phenotype, leading to suppression of cellular immunity
      and lesion progression to cancer. Humoral response after natural infection is
      inefficient, and neutralizing antibodies are not adequate in many women.
      Utilizing this knowledge, new endeavors, such as therapeutic vaccination, aim to
      stimulate cellular immune response against the virus and alter the milieu of the
      lesion. 

PMID- 24023509
TI  - Analysis of Patterns of Gene Expression Variation within and between Ethnic
      Populations in Pediatric B-ALL.
AB  - B-Precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood
      cancer. Although 80% of B-ALL patients are able to be cured, significant
      challenges persist. Significant disparities in clinical outcomes and mortality
      rates exist between racial/ethnic populations. The objective of this study was to
      determine whether gene expression levels significantly differ between ethnic
      populations. We compared gene expression levels between four ethnic populations
      (Whites, Blacks, Hispanics, and Asians) in the United States. Additionally, we
      performed network and pathway analysis to identify gene networks and pathways.
      Gene expression data involved 198 samples distributed as follows: 126 Whites, 51
      Hispanics, 13 Blacks, and 8 Asians. We identified 300 highly significantly (P <
      0.001) differentially expressed genes between the four ethnic populations. Among
      the identified genes included the genes PHF6, BRD3, CRLF2, and RNF135 which have
      been implicated in pediatric B-ALL. We identified key pathways implicated in B
      ALL including the PDGF, PI3/AKT, ERBB2-ERBB3, and IL-15 signaling pathways. 

PMID- 24023510
TI  - Decreased Hepatocyte Growth Factor (HGF) and Gamma Aminobutyric Acid (GABA) in
      Individuals with Obsessive-Compulsive Disorder (OCD).
AB  - INTRODUCTION: There is support for the role of gamma aminobutyric acid (GABA) in
      the etiology of mood disorders. Recent research has shown that hepatocyte growth
      factor (HGF) modulates GABAergic inhibition and seizure susceptibility. This
      study was designed to determine and correlate plasma levels of HGF and GABA as
      well as symptom severity in individuals with obsessive-compulsive disorder (OCD).
      SUBJECTS AND METHODS: Plasma from 15 individuals with OCD (9 males, 6 females;,
      mean age 38.7 years) and 17 neurotypical controls (10 males, 7 females; mean age
      35.2 years) was assessed for HGF, GABA, urokinase plasminogen activator (uPA),
      and urokinase plasminogen activator receptor (uPAR) concentration using enzyme
      linked immunosorbest assays ELISAs. Symptom severity was assessed in these OCD
      individuals and compared with HGF and GABA concentrations. RESULTS: In this
      preliminary study, individuals with OCD had significantly decreased HGF levels,
      decreased plasma levels of GABA and decreased uPA. We found that both uPA and
      uPAR levels correlate with HGF. Both low uPA and low uPAR levels correlate with
      high symptom severity in individuals with OCD. Low GABA levels in OCD individuals
      also correlate with high symptom severity. DISCUSSION: These results demonstrate
      a preliminary association between HGF, GABA, uPA levels, and OCD and suggest that
      plasma GABA and uPA levels are related to symptom severity in individuals with
      OCD.

PMID- 24023511
TI  - P-glycoprotein Inhibition for Optimal Drug Delivery.
AB  - P-glycoprotein (P-gp), an efflux membrane transporter, is widely distributed
      throughout the body and is responsible for limiting cellular uptake and the
      distribution of xenobiotics and toxic substances. Hundreds of structurally
      diverse therapeutic agents are substrates to it and it impedes the absorption,
      permeability, and retention of the drugs, extruding them out of the cells. It is
      overexpressed in cancer cells and accountable for obstructing cell
      internalization of chemotherapeutic agents and for developing transporter
      mediated resistance by cancer cells during anti-tumor treatments. As it
      jeopardizes the success of drug delivery and cancer targeting, strategies are
      being developed to overcome P-gp mediated drug transport. This concise review
      represents a brief discussion on P-gp mediated drug transport and how it hinders
      the success of various therapies. Its main focus is on various strategies used to
      tackle this curb in the field of drug delivery and targeting. 

PMID- 24023512
TI  - Comparison of drug survival rates for tumor necrosis factor antagonists in
      rheumatoid arthritis.
AB  - BACKGROUND: Persistence of anti-tumor necrosis factor (TNF) therapy in rheumatoid
      arthritis (RA) is an overall marker of treatment success. OBJECTIVE: To assess
      the survival of anti-TNF treatment and to define the potential predictors of drug
      discontinuation in RA, in order to verify the adequacy of current practices.
      DESIGN: An observational, descriptive, longitudinal, retrospective study.
      SETTING: The Hospital Clinico Universitario de Valladolid, Valladolid, Spain.
      PATIENTS: RA patients treated with anti-TNF therapy between January 2011 and
      January 2012. MEASUREMENTS: Demographic information and therapy assessments were
      gathered from medical and pharmaceutical records. Data is expressed as means
      (standard deviations) for quantitative variables and frequency distribution for
      qualitative variables. Kaplan-Meier survival analysis was used to assess
      persistence, and Cox multivariate regression models were used to assess potential
      predictors of treatment discontinuation. RESULTS: In total, 126 treatment series
      with infliximab (n = 53), etanercept (n = 51) or adalimumab (n = 22) were
      administered to 91 patients. Infliximab has mostly been used as a first-line
      treatment, but it was the drug with the shortest time until a change of
      treatment. Significant predictors of drug survival were: age; the anti-TNF agent;
      and the previous response to an anti-TNF drug. LIMITATION: The small sample size.
      CONCLUSION: The overall efficacy of anti-TNF drugs diminishes with time, with
      infliximab having the shortest time until a change of treatment. The management
      of biologic therapy in patients with RA should be reconsidered in order to
      achieve disease control with a reduction in costs.

PMID- 24023513
TI  - Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat.
AB  - BACKGROUND: In the present investigation, we studied the kinetics and
      biodistribution of a contrast agent consisting of poly(vinyl alcohol) (PVA)
      microbubbles containing superparamagnetic iron oxide (SPION) trapped between the
      PVA layers (SPION microbubbles). METHODS: The biological fate of SPION
      microbubbles was determined in Sprague-Dawley rats after intravenous
      administration. Biodistribution and elimination of the microbubbles were studied
      in rats using magnetic resonance imaging for a period of 6 weeks. The rats were
      sacrificed and perfusion-fixated at different time points. The magnetic resonance
      imaging results obtained were compared with histopathologic findings in different
      organs. RESULTS: SPION microbubbles could be detected in the liver using magnetic
      resonance imaging as early as 10 minutes post injection. The maximum signal was
      detected between 24 hours and one week post injection. Histopathology showed the
      presence of clustered SPION microbubbles predominantly in the lungs from the
      first time point investigated (10 minutes). The frequency of microbubbles
      declined in the pulmonary vasculature and increased in pulmonary, hepatic, and
      splenic macrophages over time, resulting in a relative shift from the lungs to
      the spleen and liver. Meanwhile, macrophages showed increasing signs of
      cytoplasmic iron accumulation, initially in the lungs, then followed by other
      organs. CONCLUSION: The present investigation highlights the biological behavior
      of SPION microbubbles, including organ distribution over time and indications for
      biodegradation. The present results are essential for developing SPION
      microbubbles as a potential contrast agent and/or a drug delivery vehicle for
      specific organs. Such a vehicle will facilitate the use of multimodality imaging
      techniques, including ultrasound, magnetic resonance imaging, and single positron
      emission computed tomography, and hence improve diagnostics, therapy, and the
      ability to monitor the efficacy of treatment.

PMID- 24023515
TI  - Comparison of anti-EGFR-Fab' conjugated immunoliposomes modified with two
      different conjugation linkers for siRNa delivery in SMMC-7721 cells.
AB  - BACKGROUND: Targeted liposome-polycation-DNA complex (LPD), mainly conjugated
      with antibodies using functionalized PEG derivatives, is an effective nanovector
      for systemic delivery of small interference RNA (siRNA). However, there are few
      studies reporting the effect of different conjugation linkers on LPD for gene
      silencing. To clarify the influence of antibody conjugation linkers on LPD, we
      prepared two different immunoliposomes to deliver siRNA in which DSPE-PEG-COOH
      and DSPE-PEG-MAL, the commonly used PEG derivative linkers, were used to
      conjugate anti-EGFR Fab' with the liposome. METHODS: First, 600 MUg of anti-EGFR
      Fab' was conjugated with 28.35 MUL of a micelle solution containing DSPE-PEG-MAL
      or DSPE-PEG-COOH, and then post inserted into the prepared LPD. Various liposome
      parameters, including particle size, zeta potential, stability, and encapsulation
      efficiency were evaluated, and the targeting ability and gene silencing activity
      of TLPD-FPC (DSPE-PEG-COOH conjugated with Fab') was compared with that of TLPD
      FPM (DSPE-PEG-MAL conjugated with Fab') in SMMC-7721 hepatocellular carcinoma
      cells. RESULTS: There was no significant difference in particle size between the
      two TLPDs, but the zeta potential was significantly different. Further, although
      there was no significant difference in siRNA encapsulation efficiency, cell
      viability, or serum stability between TLPD-FPM and TLPD-FPC, cellular uptake of
      TLPD-FPM was significantly greater than that of TLPD-FPC in EGFR-overexpressing
      SMMC-7721 cells. The luciferase gene silencing efficiency of TLPD-FPM was
      approximately three-fold high than that of TLPD-FPC. CONCLUSION: Different
      conjugation linkers whereby antibodies are conjugated with LPD can affect the
      physicochemical properties of LPD and antibody conjugation efficiency, thus
      directly affecting the gene silencing effect of TLPD. Immunoliposomes prepared by
      DSPE-PEG-MAL conjugation with anti-EGFR Fab' are more effective than TLPD
      containing DSPE-PEG-COOH in targeting hepatocellular carcinoma cells for siRNA
      delivery.

PMID- 24023514
TI  - Engineered nanomaterial uptake and tissue distribution: from cell to organism.
AB  - Improved understanding of interactions between nanoparticles and biological
      systems is needed to develop safety standards and to design new generations of
      nanomaterials. This article reviews the molecular mechanisms of cellular uptake
      of engineered nanoparticles, their intracellular fate, and their distribution
      within an organism. We have reviewed the available literature on the uptake and
      disposition of engineered nanoparticles. Special emphasis was placed on the
      analysis of experimental systems and their limitations with respect to their
      usefulness to predict the in vivo situation. The available literature confirms
      the need to study particle characteristics in an environment that simulates the
      situation encountered in biological systems. Phenomena such as protein binding
      and opsonization are of prime importance since they may have a strong impact on
      cellular internalization, biodistribution, and immunogenicity of nanoparticles in
      vitro and in vivo. Extrapolation from in vitro results to the in vivo situation
      in the whole organism remains a challenge. However, improved understanding of
      physicochemical properties of engineered nanoparticles and their influence on
      biological systems facilitates the design of nanomaterials that are safe, well
      tolerated, and suitable for diagnostic or therapeutic use in humans. 

PMID- 24023516
TI  - Managing dialysis patients who develop anemia caused by chronic kidney disease:
      focus on peginesatide.
AB  - Anemia in chronic kidney disease is a prevalent and expensive problem in the
      United States, and it is well documented that anemia worsens as glomerular
      filtration rates decline. The complications of severe anemia in this patient
      population contribute significantly to their overall morbidity with increased
      cardiovascular complications, decreased quality of life, and increased dependence
      on transfusions to maintain adequate hemoglobin levels. Erythropoietin
      stimulating agents (ESAs) have revolutionized the treatment of anemia in this
      population, but there has been a great deal of controversy surrounding the quest
      for the ideal hemoglobin target. In addition, there are economic and practice
      management implications where anemia treatment is concerned, with ongoing
      refinement of Centers for Medicare and Medicaid Services-bundled payments. One of
      the newest additions to the arsenal used to fight anemia in end-stage renal
      disease patients is peginesatide (Omontys), a synthetic, PEGylated, peptide-based
      ESA that acts by stimulating the erythropoietin receptor. The role of
      peginesatide in the future treatment of anemia in chronic kidney disease remains
      uncertain, with new safety concerns being brought to attention as it emerges on
      the market, prompting a national recall. 

PMID- 24023517
TI  - Application of liposomal technologies for delivery of platinum analogs in
      oncology.
AB  - Platinum-based chemotherapy, such as cisplatin, oxaliplatin, and carboplatin, is
      one of the most widely utilized classes of cancer therapeutics. While highly
      effective, the clinical applications of platinum-based drugs are limited by their
      toxicity profiles as well as suboptimal pharmacokinetic properties. Therefore,
      one of the key research areas in oncology has been to develop novel platinum
      analog drugs and engineer new platinum drug formulations to improve the
      therapeutic ratio further. Such efforts have led to the development of platinum
      analogs including nedaplatin, heptaplatin, and lobaplatin. Moreover,
      reformulating platinum drugs using liposomes has resulted in the development of L
      NDPP (AroplatinTM), SPI-77, LipoplatinTM, LipoxalTM, and LiPlaCis(r). Liposomes
      possess several attractive biological activities, including biocompatibility,
      high drug loading, and improved pharmacokinetics, that are well suited for
      platinum drug delivery. In this review, we discuss the various platinum drugs and
      their delivery using liposome-based drug delivery vehicles. We compare and
      contrast the different liposome platforms as well as speculate on the future of
      platinum drug delivery research. 

PMID- 24023518
TI  - Use of pioglitazone in the treatment of diabetes: effect on cardiovascular risk.
AB  - Pioglitazone and other thiazolidinediones (TZDs) initially showed great promise
      as unique receptor-mediated oral therapy for type 2 diabetes, but a host of
      serious side effects, primarily cardiovascular, have limited their utility. It is
      crucial at this point to perform a risk- benefit analysis to determine what role
      pioglitazone should play in our current treatment of type 2 diabetes and where
      the future of this class of drugs is headed. This review provides a comprehensive
      overview of the present literature. Clinical data currently available indicate
      that pioglitazone is an effective and generally well-tolerated treatment option
      for use in patients with type 2 diabetes. Pioglitazone can still reduce adverse
      cardiovascular risk. 

PMID- 24023519
TI  - Calling for help? Considering function and meaning when patients drunk-dial
      psychotherapists.
AB  - Drunk-dialing is a term documented in both popular culture and academic
      literatures to describe a behavior in which a person contacts another individual
      by phone while intoxicated. In our collective clinical experience we have found
      that clients drunk-dial their clinicians too, particularly while in substance use
      treatment, and yet there is a noticeable absence of research on the topic to
      guide clinical decision-making within a process-based understanding of these
      events. As the parameters within which psychotherapy takes place become
      increasingly technologized, a literature base to document clients' idiosyncratic
      use of technology will become increasingly necessary and useful. We provide a
      brief review of the existing research on drunk-dialing and conclude with specific
      questions to guide future research and practice. 

PMID- 24023520
TI  - The Tumor-Selective Cytotoxic Agent beta-Lapachone is a Potent Inhibitor of IDO1.
AB  - beta-lapachone is a naturally occurring 1,2-naphthoquinone-based compound that
      has been advanced into clinical trials based on its tumor-selective cytotoxic
      properties. Previously, we focused on the related 1,4-naphthoquinone
      pharmacophore as a basic core structure for developing a series of potent
      indoleamine 2,3-dioxygenase 1 (IDO1) enzyme inhibitors. In this study, we
      identified IDO1 inhibitory activity as a previously unrecognized attribute of the
      clinical candidate beta-lapachone. Enzyme kinetics-based analysis of beta
      lapachone indicated an uncompetitive mode of inhibition, while computational
      modeling predicted binding within the IDO1 active site consistent with other
      naphthoquinone derivatives. Inhibition of IDO1 has previously been shown to
      breach the pathogenic tolerization that constrains the immune system from being
      able to mount an effective anti-tumor response. Thus, the finding that beta
      lapachone has IDO1 inhibitory activity adds a new dimension to its potential
      utility as an anti-cancer agent distinct from its cytotoxic properties, and
      suggests that a synergistic benefit can be achieved from its combined cytotoxic
      and immunologic effects. 

PMID- 24023521
TI  - Role of alpha-lipoic acid in the management of anemia in patients with chronic
      renal failure undergoing hemodialysis.
AB  - INTRODUCTION: Anemia associated with chronic kidney disease is a serious
      complication necessitating expenditure of huge medical efforts and resources.
      This study investigates the role of alpha-lipoic acid (ALA) in end stage renal
      disease patients undergoing hemodialysis. By the virtue of its antioxidative
      effects, ALA is expected to act as an erythropoietin (EPO) adjuvant, and also has
      extended beneficial effects on endothelial dysfunction. METHODS: Forty-four
      patients undergoing hemodialysis and receiving EPO were randomized into two
      groups: the first group received ALA 600 mg once daily for 3 months; while the
      other group represented the control group. Parameters measured at baseline and at
      end of study were hemoglobin, EPO doses, EPO resistance index (ERI), iron store
      indices, malondialdehyde, oxidized low-density lipoprotein (ox-LDL), interleukin
      6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and asymmetric
      dimethylarginine (ADMA), as well as routine laboratory follow-up. RESULTS: EPO
      doses and ERI were significantly decreased in the treatment group, while they did
      not change in the control group. Hemoglobin, iron store indices, malondialdehyde,
      oxidized ox-LDL, IL-6, TNF-alpha, and ADMA were similar in both treatment and
      control groups at baseline, and did not change by the end of study period.
      Likewise, routine laboratory measures were not affected by the treatment.
      CONCLUSION: ALA could be used in hemodialysis patients to reduce requirements for
      EPO. However, larger and longer term studies are required to clarify the exact
      role of ALA in hemodialysis as well as in pre-hemodialysis patients.

PMID- 24023522
TI  - A higher frequency of lumbar ossification of the posterior longitudinal ligament
      in elderly in an outpatient clinic in Japan.
AB  - PURPOSE: Little is known about the prevalence and epidemiological characteristics
      of lumbar ossification of the posterior longitudinal ligament (OPLL). We analyzed
      the rate of lumbar OPLL in an outpatient unit where primary care physicians are
      working in Japan, to better understand the epidemiological characteristics of the
      disease. METHODS: We analyzed consecutive, first-time visiting outpatients who
      received abdominal and pelvic computed tomography (CT) scan at the Department of
      General Medicine, Asahikawa Medical University Hospital, Japan, between April
      2009 and March 2012. Each parameter such as age, sex, and clinical presentation
      was investigated. RESULTS: Out of 393 patients who underwent abdominal and pelvic
      CT scan, 33 (8.4%) were diagnosed as lumbar OPLL. When compared with patients
      without lumbar OPLL (n = 360), there was no significant difference in gender,
      body mass index (BMI), presence of hypertension, diabetes mellitus or
      hyperlipidemia, and smoking habit, while the age in patients with lumbar OPLL was
      significantly higher. CONCLUSION: These results suggest for the first time that
      lumbar OPLL is frequently observed in elderly people in the primary care setting,
      in Japan.

PMID- 24023523
TI  - Targeting CD19 in B-cell lymphoma: emerging role of SAR3419.
AB  - Non-Hodgkin lymphoma symbolizes a heterogeneous group of diseases resulting from
      malignant transformation of lymphocytes with differing patterns of behavior and
      responses to treatment. The potential curability of non-Hodgkin lymphoma differs
      among the various histologic subtypes and is associated in part with the stage at
      presentation. CD19 antigen is a type I transmembrane glycoprotein belonging to
      the immunoglobulin Ig superfamily. CD19 is specifically expressed in normal and
      neoplastic B-cells. Recent study showed that in a mouse model, CD19 and c-Myc
      synergize functionally to accelerate B-cell lymphomagenesis, which is associated
      with increased disease severity. Specificity is the most important challenge in
      cancer therapeutics. Antibody-drug conjugates have the prospect of enhancing the
      therapeutic efficacy over unconjugated monoclonal antibodies through the
      selective delivery of cytotoxic agents to cancer cells. The ubiquitous expression
      of CD19 in these tumors, especially at an earlier stage and the property of
      efficient internalization, makes CD19 an attractive and affective target for
      antibody-drug conjugate therapy as compared to CD20. SAR3419 (huB4-DM4) is a
      novel antibody-drug conjugate that is composed of a humanized monoclonal IgG1
      anti-CD19 antibody (huB4) attached to the potent cytotoxic drug, a maytansine
      derivative (DM4), through a cleavable disulfide cross-linking agent N
      Succinimidyl-4-2-pyridyldithio butanoic acid (SPDB). The preclinical efficacy of
      maytansine derivative-anti-CD19 conjugate was demonstrated in our laboratory, and
      SAR3419 was found to be more effective than CHOP in a xenograft model. Phase I
      trials have also been conducted on the basis of preclinical studies that
      demonstrated promising antitumor activity with acceptable safety results in human
      B-cell lymphoma models. Additional trials are ongoing and will provide additional
      insight into the full potential of this novel drug. 

PMID- 24023524
TI  - Broad spectrum of skeletal malformation complex in patients with cleidocranial
      dysplasia syndrome: radiographic and tomographic study.
AB  - PURPOSE: Cleidocranial dysplasia is an autosomal dominant disorder characterized
      by defective ossification of the intramembraneous ossification (primarily the
      clavicles, cranium, and pelvis), and it is caused by mutations in the RUNX2 gene
      that is responsible for osteoblast differentiation. Spine deformities were of
      progressive nature and considered to be the major orthopedic abnormalities
      encountered in our practice in patients with cleidocranial dysplasia. We aimed to
      further delineate the underlying spine pathology and its etiological
      understanding. Extraspinal deformities were dealt with respectively. MATERIAL AND
      METHODS: In this paper, we describe 7 patients who were consistent with the
      phenotypic and the genotypic characterization of cleidocranial dysplasia.
      Reformatted computed tomography (CT) scans have been applied in several instances
      to further understand the underlying pathology of progressive spine tilting.
      Radiographs were sufficient to illustrate other skeletal malformations. RESULTS:
      Anatomical survey demonstrates that a broad spectrum of frequently unrecognized
      orthopedic aberrations were encountered. We believe that torticollis has evolved
      in connection with the persistence of synchondrosis of the skull base and the
      upper cervical spine and these are strongly correlated to the well-known
      pathology of posterior occipital synchondrosis. Similarly, scoliosis and
      kyphoscoliosis resulted from the pathologic aberration of the cartilaginous stage
      of disrupted embryological development. All our results are discussed for the
      first time. Coxa vara, patellar dysplasia, and genu valgum were observed as
      extraspinal deformities. CONCLUSION: This paper includes for the first time the
      anatomical analysis of the malformation complex of the craniocervical and the
      entire spine in patients with cleidocranial dysplasia. Reformatted CT scan was
      the modality of choice. We were able to illustrate that the persistence of skull
      base and the cervical spine synchondrosis were correlated with the pathological
      mechanism of the posterior occipital synchondrosis. Therefore, injuries to the
      craniocervical region in these patients might lead to a wide range of dreadful
      complications, ranging from complete atlanto-occipital or atlanto-axial
      dislocation to nondisplaced occipital condyle avulsion fractures with the
      possibility of morbid and or mortal outcome. On the other hand, the persistence
      of a cartilaginous spine was the reason behind the progressive spine tilting.
      This pathological form can be considered as a notoriously unpredictable
      malformation complex. The value of presenting these patients is to demonsterate
      that the genotype is not a precise index to assess the severity and the natural
      history of the phenotype.

PMID- 24023525
TI  - Non-Steroidal Anti-Inflammatory Drugs, Variation in Inflammatory Genes, and
      Aggressive Prostate Cancer.
AB  - Increasing evidence suggests that prostatic inflammation plays a key role in the
      development of prostate cancer. It remains controversial whether non-steroidal
      anti-inflammatory drugs (NSAIDs) reduce the risk of prostate cancer. Here, we
      investigate how a previously reported inverse association between NSAID use and
      the risk of aggressive prostate cancer is modulated by variants in several
      inflammatory genes. We found that NSAIDs may have differential effects on
      prostate cancer development, depending on one's genetic makeup. Further study of
      these inflammatory pathways may clarify the mechanisms through which NSAIDs
      impact prostate cancer risk.

PMID- 24023526
TI  - Variation of photosynthesis, fatty acid composition, ATPase and acid phosphatase
      activities, and anatomical structure of two tea (Camellia sinensis (L.) O.
      Kuntze) cultivars in response to fluoride.
AB  - The changes of photosynthetic parameters, water use efficiency (WUE), fatty acid
      composition, chlorophyll (Chl) content, malondialdehyde (MDA) content, ATPase and
      acid phosphatase activities, fluoride (F) content, and leaf anatomical structure
      of two tea cultivars, "Pingyangtezao" (PY) and "Fudingdabai" (FD), after F
      treatments were investigated. The results show that net photosynthetic rate
      (P(n)), stomatal conductance (g(s)), and transpiration rate (E) significantly
      decreased in both cultivars after 0.3 mM F treatment, but FD had higher P(n),
      g(s), and WUE and lower E than PY. Chl content in PY significantly decreased
      after 0.2 and 0.3 mM F treatments, while no significant changes were observed in
      FD. The proportions of shorter chain and saturated fatty acids increased and
      those of longer chain and unsaturated fatty acids decreased in both cultivars
      under F treatments. The contents of MDA increased after F treatments but were
      higher in PY than in FD. In addition, F treatments decreased the activities of
      ATPase and acid phosphatase and increased F content in both cultivars; however,
      compared with PY, FD showed higher enzymatic activities and lower F content in
      roots and leaves. Leaf anatomical structure in FD indicated that cells in leaf
      midrib region were less injured by F than in PY.

PMID- 24023527
TI  - Study on the effect of blood content on diffuse reflectance spectra of basal cell
      carcinoma skin tissue.
AB  - Diffuse reflectance spectrum as a noninvasive method has been widely used to
      study the optical properties of cutaneous skin tissue. In this work, we optimized
      an eight-layered optical model of basal cell carcinoma skin tissue to study its
      optical properties. Based on the model, the diffuse reflectance spectra were
      reconstructed in visible wavelength range by Monte Carlo methods. After different
      blood contents were added to the optical model, the contribution of blood to
      diffuese reflectance spectra was investigated theoretically. The ratios of basal
      cell carcinoma skin and normal skin tissue were also calculated for both
      experimental result and rebuilt results to testify the theoretical reasonability
      of the model and methods. 

PMID- 24023528
TI  - Antitumor activity of human hydatid cyst fluid in a murine model of colon cancer.
AB  - This study evaluates the antitumor immune response induced by human hydatic cyst
      fluid (HCF) in an animal model of colon carcinoma. We found that anti-HCF
      antibodies were able to identify cell surface and intracellular antigens in CT26
      colon cancer cells. In prophylactic tumor challenge experiments, HCF vaccination
      was found to be protective against tumor formation for 40% of the mice (P =
      0.01). In the therapeutic setting, HCF vaccination induced tumor regression in
      40% of vaccinated mice (P = 0.05). This vaccination generated memory immune
      responses that protected surviving mice from tumor rechallenge, implicating the
      development of an adaptive immune response in this process. We performed a
      proteomic analysis of CT26 antigens recognized by anti-HCF antibodies to analyze
      the immune cross-reactivity between E. granulosus (HCF) and CT26 colon cancer
      cells. We identified two proteins: mortalin and creatine kinase M-type.
      Interestingly, CT26 mortalin displays 60% homology with E. granulosus hsp70. In
      conclusion, our data demonstrate the capacity of HCF vaccination to induce
      antitumor immunity which protects from tumor growth in an animal model. This new
      antitumor strategy could open new horizons in the development of highly
      immunogenic anticancer vaccines. 

PMID- 24023529
TI  - Variations in the levels of mulberroside A, oxyresveratrol, and resveratrol in
      mulberries in different seasons and during growth.
AB  - This study aimed to investigate the composition of three major stilbenes
      (mulberroside A, oxyresveratrol, and resveratrol) in different portions of
      mulberries collected in different seasons and their change molds during growth by
      high-performance liquid chromatography. Mulberroside A levels were the highest in
      the bark and roots of Morus atropurpurea Roxb, Morus alba Linn, and Morus
      latifolia Poir. Oxyresveratrol levels were the highest in roots and stem. Both of
      these high levels were in September. The amount of resveratrol was very low in
      all samples. In the stem, Morus latifolia Poir contained more mulberroside A than
      the other two mulberries. Mulberroside A was not detected in the leaves of the
      three mulberries. In Morus atropurpurea Roxb seedlings, the root tended to
      contain more of the three stilbenes than leaves. The temporal peaks of
      resveratrol were always ahead of those for oxyresveratrol. The levels of the
      stilbenes varied in different portions of the varieties of mulberries collected
      in different season and in the seedlings of Morus atropurpurea Roxb. 

PMID- 24023530
TI  - Developing dynamic digital image techniques with continuous parameters to detect
      structural damage.
AB  - Several earthquakes with strong magnitude occurred globally at various locations,
      especially the unforgettable tsunami disaster caused by the earthquake in
      Indonesia and Japan. If the characteristics of structures can be well understood
      to implement new technology, the damages caused by most natural disasters can be
      significantly alleviated. In this research, dynamic digital image correlation
      method for using continuous parameter is applied for developing a low-cost
      digital image correlation coefficient method with advanced digital cameras and
      high-speed computers. The experimental study using cantilever test object with
      defect control confirms that the vibration mode calculated using this proposed
      method can highly express the defect locations. This proposed method combined
      with the sensitivity of Inter-Story Drift Mode Shape, IDMS, can also reveal the
      damage degree of damage structure. These test and analysis results indicate that
      this proposed method is high enough for applying to achieve the object of real
      time online monitoring of structure. 

PMID- 24023531
TI  - Comparison of ultrasonic and pneumatic intracorporeal lithotripsy techniques
      during percutaneous nephrolithotomy.
AB  - OBJECTIVES: To compare the effectiveness and safety of ultrasonic and pneumatic
      lithotripters in the treatment of renal stone disease. MATERIALS AND METHODS: A
      total of 227 consecutive percutaneous nephrolithotomy procedures for renal
      calculi were performed. In 107 patients ultrasonic lithotriptors were used (group
      I) and in 83 patients pneumatic lithotriptors were used (group II). In the
      remaining 37 patients, stones were managed with both pneumatic and ultrasonic
      lithotripters. Follow-up studies included intravenous urography (IVU) and/or
      computed tomography (CT). RESULTS: The mean operative time and duration of
      hospitalization were similar between the groups. In the ultrasonic treatment
      group, 100 (96.9%) patients were stone-free on postoperative day 1 and 5 (4.6%)
      went on to undergo an additional treatment modality, resulting in a total stone
      free rate of 97.2%. In the pneumatic lithotripsy group, 68 (81.9%) patients were
      stone-free after the primary procedure on the first day and 15 (18.1%) went on to
      undergo an additional treatment modality, resulting in a stone-free rate of
      91.5%. The final stone-free rates at 3 months postoperatively in groups I, II,
      and III were 97.2%, 91.5%, and 87.9%, respectively (P = 0.826). CONCLUSIONS: We
      conclude that both ultrasonic and pneumatic lithotripters are effective and safe
      for intracorporeal lithotripsy. However, the ultrasonic lithotripter provides
      higher stone-free rates with similar morbidity compared with pneumatic devices.

PMID- 24023532
TI  - Real-time EEG-based happiness detection system.
AB  - We propose to use real-time EEG signal to classify happy and unhappy emotions
      elicited by pictures and classical music. We use PSD as a feature and SVM as a
      classifier. The average accuracies of subject-dependent model and subject
      independent model are approximately 75.62% and 65.12%, respectively. Considering
      each pair of channels, temporal pair of channels (T7 and T8) gives a better
      result than the other area. Considering different frequency bands, high-frequency
      bands (Beta and Gamma) give a better result than low-frequency bands. Considering
      different time durations for emotion elicitation, that result from 30 seconds
      does not have significant difference compared with the result from 60 seconds.
      From all of these results, we implement real-time EEG-based happiness detection
      system using only one pair of channels. Furthermore, we develop games based on
      the happiness detection system to help user recognize and control the happiness. 

PMID- 24023533
TI  - Normal anatomical features and variations of the vertebrobasilar circulation and
      its branches: an analysis with 64-detector row CT and 3T MR angiographies.
AB  - PURPOSE: To determine the normal anatomical features and variations of the
      vertebrobasilar circulation and its branches in patients who underwent
      multidetector computed tomography (CT) or magnetic resonance (MR) angiographies
      of the brain. METHODS: 135 patients (male, 83 and female, 52; mean age, 50.1
      years) who underwent CT (n = 71) or MR (n = 64) angiographies of the
      vertebrobasilar vasculature for various reasons were analyzed retrospectively.
      The right and left distal vertebral arteries (VAs), posterior inferior cerebellar
      arteries (PICAs), anterior inferior cerebellar arteries (AICAs), superior
      cerebellar arteries (SCAs), posterior cerebral arteries (PCAs), and posterior
      communicating arteries (PCoAs) were analyzed individually. RESULTS: In 24.4% of
      the cases (33/135) right PICA, in 19.3% of the cases (26/135) left PICA, in 17.8%
      of the cases (24/135) right AICA, and in 18.5% of the cases (25/135) left AICA
      were absent. In cases without PICA or AICA, there was a statistically
      significant, moderately or well-developed AICA or PICA on the same side,
      respectively (P < 0.001). The most common variation was isolated absence of right
      PICA and was seen in 17.8% of the cases. CONCLUSIONS: The anatomic features of
      the branches of the vertebrobasilar circulation may be different from well-known
      normal anatomy. CT and MR angiographies allow a precise and detailed evaluation
      of vertebrobasilar circulation.

PMID- 24023534
TI  - Fractional solutions of Bessel equation with N-method.
AB  - This paper deals with the design fractional solution of Bessel equation. We
      obtain explicit solutions of the equation with the help of fractional calculus
      techniques. Using the N-fractional calculus operator N(nu) method, we derive the
      fractional solutions of the equation.

PMID- 24023536
TI  - Crack propagation analysis using acoustic emission sensors for structural health
      monitoring systems.
AB  - Aerospace systems are expected to remain in service well beyond their designed
      life. Consequently, maintenance is an important issue. A novel method of
      implementing artificial neural networks and acoustic emission sensors to form a
      structural health monitoring (SHM) system for aerospace inspection routines was
      the focus of this research. Simple structural elements, consisting of flat
      aluminum plates of AL 2024-T3, were subjected to increasing static tensile
      loading. As the loading increased, designed cracks extended in length, releasing
      strain waves in the process. Strain wave signals, measured by acoustic emission
      sensors, were further analyzed in post-processing by artificial neural networks
      (ANN). Several experiments were performed to determine the severity and location
      of the crack extensions in the structure. ANNs were trained on a portion of the
      data acquired by the sensors and the ANNs were then validated with the remaining
      data. The combination of a system of acoustic emission sensors, and an ANN could
      determine crack extension accurately. The difference between predicted and actual
      crack extensions was determined to be between 0.004 in. and 0.015 in. with 95%
      confidence. These ANNs, coupled with acoustic emission sensors, showed promise
      for the creation of an SHM system for aerospace systems.

PMID- 24023535
TI  - Effects of environmental factors on nutrients release at sediment-water interface
      and assessment of trophic status for a typical shallow lake, northwest China.
AB  - Surface sediment and water samples were collected from Daihai Lake to study the
      biogeochemical characteristics of nitrogen and phosphorus, to estimate the loads
      of these nutrients, and to assess their effects on water quality. The contents
      and spatial distributions of total phosphorus (TP), total nitrogen (TN), and
      different nitrogen forms in sediments were analyzed. The results showed that
      concentrations of TN and TP in surface sediments ranged from 0.27 to 1.78 g/kg
      and from 558.31 to 891.29 mg/kg, respectively. Ratios of C:N ranged between 8.2
      and 12.1, which indicated that nitrogen accumulated came mainly from terrestrial
      source. Ratios of N:P in all sampling sites were below 10, which indicated that N
      was the limiting nutrient for algal growth in this lake. Effects of environment
      factors on the release of nitrogen and phosphorus in lake sediments were also
      determined; high pH values could encourage the release of nitrogen and
      phosphorus. Modified Carlson's trophic state index (TSI(M)) and comprehensive
      trophic state index (TSI(C)) were applied to ascertain the trophic classification
      of the studied lake, and the values of TSI(M) and TSI(C) ranged from 53.72 to
      70.61 and from 47.73 to 53.67, respectively, which indicated that the Daihai Lake
      was in the stage of hypereutropher.

PMID- 24023537
TI  - A feasibility randomised controlled trial of the New Orleans intervention for
      infant mental health: a study protocol.
AB  - Child maltreatment is associated with life-long social, physical, and mental
      health problems. Intervening early to provide maltreated children with safe,
      nurturing care can improve outcomes. The need for prompt decisions about
      permanent placement (i.e., regarding adoption or return home) is internationally
      recognised. However, a recent Glasgow audit showed that many maltreated children
      "revolve" between birth families and foster carers. This paper describes the
      protocol of the first exploratory randomised controlled trial of a mental health
      intervention aimed at improving placement permanency decisions for maltreated
      children. This trial compares an infant's mental health intervention with the new
      enhanced service as usual for maltreated children entering care in Glasgow. As
      both are new services, the trial is being conducted from a position of equipoise.
      The outcome assessment covers various fields of a child's neurodevelopment to
      identify problems in any ESSENCE domain. The feasibility, reliability, and
      developmental appropriateness of all outcome measures are examined. Additionally,
      the potential for linkage with routinely collected data on health and social care
      and, in the future, education is explored. The results will inform a definitive
      randomised controlled trial that could potentially lead to long lasting benefits
      for the Scottish population and which may be applicable to other areas of the
      world. This trial is registered with ClinicalTrials.gov (NC01485510). 

PMID- 24023538
TI  - Computational representation of white matter fiber orientations.
AB  - We present a new methodology based on directional data clustering to represent
      white matter fiber orientations in magnetic resonance analyses for high angular
      resolution diffusion imaging. A probabilistic methodology is proposed for
      estimating intravoxel principal fiber directions, based on clustering directional
      data arising from orientation distribution function (ODF) profiles. ODF
      reconstructions are used to estimate intravoxel fiber directions using mixtures
      of von Mises-Fisher distributions. The method focuses on clustering data on the
      unit sphere, where complexity arises from representing ODF profiles as
      directional data. The proposed method is validated on synthetic simulations, as
      well as on a real data experiment. Based on experiments, we show that by
      clustering profile data using mixtures of von Mises-Fisher distributions it is
      possible to estimate multiple fiber configurations in a more robust manner than
      currently used approaches, without recourse to regularization or sharpening
      procedures. The method holds promise to support robust tractographic
      methodologies and to build realistic models of white matter tracts in the human
      brain. 

PMID- 24023539
TI  - Microwave imaging of human forearms: pilot study and image enhancement.
AB  - We present a pilot study using a microwave tomography system in which we image
      the forearms of 5 adult male and female volunteers between the ages of 30 and 48.
      Microwave scattering data were collected at 0.8 to 1.2 GHz with 24 transmitting
      and receiving antennas located in a matching fluid of deionized water and table
      salt. Inversion of the microwave data was performed with a balanced version of
      the multiplicative-regularized contrast source inversion algorithm formulated
      using the finite-element method (FEM-CSI). T1-weighted MRI images of each
      volunteer's forearm were also collected in the same plane as the microwave
      scattering experiment. Initial "blind" imaging results from the utilized
      inversion algorithm show that the image quality is dependent on the thickness of
      the arm's peripheral adipose tissue layer; thicker layers of adipose tissue lead
      to poorer overall image quality. Due to the exible nature of the FEM-CSI
      algorithm used, prior information can be readily incorporated into the microwave
      imaging inversion process. We show that by introducing prior information into the
      FEM-CSI algorithm the internal anatomical features of all the arms are resolved,
      significantly improving the images. The prior information was estimated manually
      from the blind inversions using an ad hoc procedure. 

PMID- 24023540
TI  - Evaluation of extended interval dosing aminoglycosides in the morbidly obese
      population.
AB  - Aminoglycoside dosing has been studied in the obese population, typically
      recommending an adjusted weight utilizing a 40% dosing weight correction factor
      (IBW + 0.4 * (TBW-IBW)). These studies included limited numbers of morbidly obese
      patients and were not done in the era of extended interval aminoglycoside dosing.
      Here, we report a retrospective evaluation of morbidly obese patients receiving
      gentamicin or tobramycin at our hospital. The objective of this study was to
      evaluate the accuracy of the commonly recommended adjusted weight for weight
      based dosing. There were 31 morbidly obese patients who received gentamicin or
      tobramycin 5-7 mg/kg every 24 hours using a 40% dosing weight correction factor.
      Our institution utilizes 16-hour postdose concentrations to monitor extended
      interval aminoglycosides. Twenty-two of the 31 patients (71%) achieved an
      appropriate serum drug concentration. Four patients (13%) were found to be
      supratherapeutic and 5 patients (16%) subtherapeutic. The only variable that
      correlated with supratherapeutic levels was older age (P = 0.0378). Our study
      helps to validate the current dosing weight correction factor (40%) in the
      morbidly obese population. We recommend caution when dosing aminoglycosides in
      morbidly obese patients who are of older age. 

PMID- 24023541
TI  - The current role of endourologic management of renal transplantation
      complications.
AB  - Introduction. Complications following renal transplantation include ureteral
      obstruction, urinary leak and fistula, urinary retention, urolithiasis, and
      vesicoureteral reflux. These complications have traditionally been managed with
      open surgical correction, but minimally invasive techniques are being utilized
      frequently. Materials and Methods. A literature review was performed on the use
      of endourologic techniques for the management of urologic transplant
      complications. Results. Ureterovesical anastomotic stricture is the most common
      long-term urologic complication following renal transplantation. Direct vision
      endoureterotomy is successful in up to 79% of cases. Urinary leak is the most
      frequent renal transplant complication early in the postoperative period. Up to
      62% of patients have been successfully treated with maximal decompression
      (nephrostomy tube, ureteral stent, and Foley catheter). Excellent outcomes have
      been reported following transurethral resection of the prostate shortly after
      transplantation for patients with urinary retention. Vesicoureteral reflux after
      renal transplant is common. Deflux injection has been shown to resolve reflux in
      up to 90% of patients with low-grade disease in the absence of high pressure
      voiding. Donor-gifted and de novo transplant calculi may be managed with shock
      wave, ureteroscopic, or percutaneous lithotripsy. Conclusions. Recent advances in
      equipment and technique have allowed many transplant patients with complications
      to be effectively managed endoscopically. 

PMID- 24023543
TI  - Coronary artery fistula presenting as unstable angina pectoris in patients with
      antiphospholipid syndrome.
AB  - The cardiovascular system is one of the primary targets in patients with
      antiphospholipid syndrome. The valves are the most frequently affected.
      Atherosclerosis and coronary thrombosis are also seen. The risk of acute coronary
      syndrome is 10 times higher in patients with APS. We present an APS patient case
      who was hospitalized with acute coronary syndrome and who was later found to have
      coronary artery fistula. 

PMID- 24023544
TI  - Anaesthesia for tracheobronchial stent insertion using an laryngeal mask airway
      and high-frequency jet ventilation.
AB  - An approach which promotes a rapid return to spontaneous respiration after
      tracheobronchial stent (TBS) insertion is considered the optimal one and is a
      belief shared by anaesthetists, respiratory physicians, and surgeons alike
      (Calvey and William (2008)). The value of the laryngeal mask airway (LMA),
      followed by use of the Monsoon 111 Acutronic jet ventilator pressure limiting
      system of ventilation, for the deployment of stents in the three individual cases
      that of tracheoesophageal fistula, a bronchoesophageal fistula, and tracheal
      compression from an invading oesophageal malignant tumour are reported. The roles
      of target controlled anaesthesia, high-frequency jet ventilation (HFJV), and the
      laryngeal mask airway in optimising the surgical field and reducing the risk of
      bronchospasm at emergence are advantages of this technique. 

PMID- 24023542
TI  - Periprosthetic joint infections.
AB  - Implantation of joint prostheses is becoming increasingly common, especially for
      the hip and knee. Infection is considered to be the most devastating of
      prosthesis-related complications, leading to prolonged hospitalization, repeated
      surgical intervention, and even definitive loss of the implant. The main risk
      factors to periprosthetic joint infections (PJIs) are advanced age, malnutrition,
      obesity, diabetes mellitus, HIV infection at an advanced stage, presence of
      distant infectious foci, and antecedents of arthroscopy or infection in previous
      arthroplasty. Joint prostheses can become infected through three different
      routes: direct implantation, hematogenic infection, and reactivation of latent
      infection. Gram-positive bacteria predominate in cases of PJI, mainly
      Staphylococcus aureus and Staphylococcus epidermidis. PJIs present characteristic
      signs that can be divided into acute and chronic manifestations. The main imaging
      method used in diagnosing joint prosthesis infections is X-ray. Computed
      tomography (CT) scan may assist in distinguishing between septic and aseptic
      loosening. Three-phase bone scintigraphy using technetium has high sensitivity,
      but low specificity. Positron emission tomography using fluorodeoxyglucose (FDG
      PET) presents very divergent results in the literature. Definitive diagnosis of
      infection should be made by isolating the microorganism through cultures on
      material obtained from joint fluid puncturing, surgical wound secretions,
      surgical debridement procedures, or sonication fluid. Success in treating PJI
      depends on extensive surgical debridement and adequate and effective antibiotic
      therapy. Treatment in two stages using a spacer is recommended for most chronic
      infections in arthroplasty cases. Treatment in a single procedure is appropriate
      in carefully selected cases. 

PMID- 24023545
TI  - Wnt1 Accelerates an Ex Vivo Expansion of Human Cord Blood CD34(+)CD38(-) Cells.
AB  - Cord blood hematopoietic stem cells (CB-HSCs) transplantation has been increasing
      gradually with facing the limitation of insufficient quantity of HSCs in each CB
      unit. Therefore, efficient expansion methods which can maintain stem cell
      characteristics are needed. In this study, umbilical CB-CD34(+) cells were
      cultured in two different cytokine cocktails: 4 factors (4F = Flt3-L, SCF, IL-6,
      and TPO) and 5 factors (5F = Wnt1 + 4F) in both serum and serum-free media. The
      data revealed that the best condition to accelerate an expansion of CD34(+)CD38(
      ) cells was serum-free culture condition supplemented with 5F (5F KSR). This
      condition yielded 24.3 +/- 2.1 folds increase of CD34(+)CD38(-) cells. The
      expanded cells exhibited CD34(+) CD38(-) CD133(+) CD71(low) CD33(low) CD3(-)
      CD19(-) markers, expressed nanog, oct3/4, c-myc, and sox2 genes, and maintained
      differentiation potential into lymphoid, erythroid and myeloid lineages. The
      achievement of CD34(+)CD38(-) cells expansion may overcome an insufficient
      quantity of the cells leading to the improvement of the stem cell
      transplantation. Altogether, our findings highlight the role of Wnt1 and the new
      culture condition in stimulating hematopoietic stem/progenitor cells expansion
      which may offer a new therapeutic avenue for cord blood transplantation,
      regenerative medicine, stem cell bank applications, and other clinical
      applications in the future. 

PMID- 24023547
TI  - Roles of matrix metalloproteinases and their targets in epileptogenesis and
      seizures.
AB  - Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases
      (TIMPs) remodel the pericellular environment by regulating the cleavage of
      extracellular matrix proteins, cell surface components, neurotransmitter
      receptors, and growth factors, which together regulate cell adhesion,
      synaptogenesis, synaptic plasticity, and long-term potentiation. Increased MMP
      activity and dysregulation of the balance between MMPs and TIMPs have also been
      implicated in various pathological conditions. Recent studies have suggested that
      prolonged seizures are associated with high MMP levels in serum and neural
      tissues, and certain extracellular macromolecule targets may influence the
      pathogenesis of epilepsy and seizure. In this review, we discuss the roles of MMP
      activation in animal models of epilepsy. 

PMID- 24023548
TI  - Use of repetitive transcranial magnetic stimulation for treatment in psychiatry.
AB  - The potential of noninvasive neurostimulation by repetitive transcranial magnetic
      stimulation (rTMS) for improving psychiatric disorders has been studied
      increasingly over the past two decades. This is especially the case for major
      depression and for auditory-verbal hallucinations in schizophrenia. The present
      review briefly describes the background of this novel treatment modality and
      summarizes evidence from clinical trials into the efficacy of rTMS for depression
      and hallucinations. Evidence for efficacy in depression is stronger than for
      hallucinations, although a number of studies have reported clinically relevant
      improvements for hallucinations too. Different stimulation parameters (frequency,
      duration, location of stimulation) are discussed. There is a paucity of research
      into other psychiatric disorders, but initial evidence suggests that rTMS may
      also hold promise for the treatment of negative symptoms in schizophrenia,
      obsessive compulsive disorder and post-traumatic stress disorder. It can be
      concluded that rTMS induces alterations in neural networks relevant for
      psychiatric disorders and that more research is needed to elucidate efficacy and
      underlying mechanisms of action. 

PMID- 24023549
TI  - Effect of aripiprazole on cognitive function and hyperprolactinemia in patients
      with schizophrenia treated with risperidone.
AB  - OBJECTIVE: This study aimed to assess the efficacy of aripiprazole for the
      management of cognitive impairments and hyperprolactinemia in patients with
      schizophrenia on a stable dose of risperidone. METHODS: Thirty-five subjects
      stabilized on risperidone (3-6 mg/day) for a minimum of 3 months were enrolled in
      a double-blind, placebo-controlled phase for 12 weeks and an open-label phase for
      another 12 weeks. Subjects were randomly assigned to receive 10 mg/day
      aripiprazole (n=17) or placebo (n=18). Over the following 12 weeks, the the
      aripiprazole group received a flexible dose of aripiprazole while tapering
      risperidone. At baseline, week 12, and week 24, subjects were evaluated using the
      Positive and Negative Syndrome Scale (PANSS), Extrapyramidal Syndrome Rating
      Scale (ESRS), and standardized neuropsychological assessments. Serum prolactin
      levels were checked at baseline, week 1, week 2, and week 24. RESULTS: The mean
      change in total PANSS and cognitive function test scores between baseline and
      endpoint were similar in the aripiprazole and placebo groups. Scores on the ESRS
      and negative subscale of PANSS differed significantly between groups in both
      phases of the study (p<0.05), indicating a positive effect of aripiprazole.
      Compared with placebo, aripiprazole significantly reduced mean baseline serum
      prolactin levels within 1 week (p=0.015). CONCLUSION: Adjunctive treatment with
      and switching to aripiprazole were not associated with improved cognitive
      function in patients with schizophrenia receiving risperidone; however,
      aripiprazole treatment decreased negative symptoms and risperidone-induced motor
      side effects and lowered serum prolactin levels.

PMID- 24023546
TI  - Cellular kinetics of perivascular MSC precursors.
AB  - Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor
      cells have been widely investigated for regenerative medicine and deemed
      promising in clinical applications. In order to further improve MSC-based stem
      cell therapeutics, it is important to understand the cellular kinetics and
      functional roles of MSCs in the dynamic regenerative processes. However, due to
      the heterogeneous nature of typical MSC cultures, their native identity and
      anatomical localization in the body have remained unclear, making it difficult to
      decipher the existence of distinct cell subsets within the MSC entity. Recent
      studies have shown that several blood-vessel-derived precursor cell populations,
      purified by flow cytometry from multiple human organs, give rise to bona fide
      MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like
      stem/progenitor cells. Using individually purified MSC-like precursor cell
      subsets, we and other researchers have been able to investigate the differential
      phenotypes and regenerative capacities of these contributing cellular
      constituents in the MSC pool. In this review, we will discuss the identification
      and characterization of perivascular MSC precursors, including pericytes and
      adventitial cells, and focus on their cellular kinetics: cell adhesion,
      migration, engraftment, homing, and intercellular cross-talk during tissue repair
      and regeneration. 

PMID- 24023550
TI  - Association between FAT Gene and Schizophrenia in the Korean Population.
AB  - OBJECTIVE: The aim of this study was to investigate the genetic association of
      the FAT gene with schizophrenia in the Korean population, as well as analyzing
      the association of FAT gene with clinical variables. METHODS: Four variants
      within the FAT gene were investigated in 189 patients with schizophrenia and 119
      healthy controls (rs2306987 A/C, rs2306990 T/C, rs2637777 G/T, and rs2304865
      G/C). RESULTS: Significant association at the rs273777 with schizophrenia was
      observed; however, rs2306987, rs2306990, and rs2304865 were not associated with
      schizophrenia. Haplotype analyses revealed that the haplotype A/T/T/G was
      associated with a significantly protective effect. Sliding window analysis
      (rs2637777 G/T and rs2304865 G/C) revealed the more common T/G haplotype,
      included in the A/T/T/G protective combination, showed a small protective effect,
      in particular the effect was due to the rs273777 T variant (minor allele).
      CONCLUSION: The present finding suggests that FAT polymorphism may play a
      putative role in the susceptibility to schizophrenia in the Korean population.
      Further studies using a larger number of subjects should be performed to
      determine whether the FAT gene polymorphism may be truly involved in the
      development of schizophrenia.

PMID- 24023551
TI  - Comparison of aripiprazole and other atypical antipsychotics for pediatric
      bipolar disorder: a retrospective chart review of efficacy and tolerability.
AB  - OBJECTIVE: This study compared the efficacy and tolerability of aripiprazole with
      that of other atypical antipsychotics by examining patients with pediatric
      bipolar disorder (PBD) at a child and adolescent psychiatric clinic in a
      university hospital in Korea. METHODS: We reviewed the medical records of 127
      pediatric patients with bipolar disorder aged 4-18 years treated at Department of
      Child and Adolescent Psychiatric, Yonsei University Severance Hospital between
      January 2010 and October 2011 to collect demographic and clinical data. Using the
      Clinical Global Impression (CGI) scales, we evaluated levels of severity of and
      improvements in symptoms at the first, second, third, fourth, and fifth hospital
      visits. RESULTS: The mean age of patients was 12.29+/-3.47 years. The sample
      included 91 (71.7%) male and 36 (28.3%) female patients. Aripiprazole was
      prescribed to 62 (48.8%) patients, risperidone to 52 (40.9%), quetiapine to 11
      (8.7%), and paliperidone to two (1.6%). Patients treated with aripiprazole had
      lower CGI-Severity (CGI-S) scores than did patients treated with other atypical
      antipsychotics at the second and third visits. The CGI-Improvement (CGI-I) scores
      of patients treated with aripiprazole were lower at the second visit. Treatment
      with atypical antipsychotics was well tolerated, and no serious or fatal side
      effects were observed. CONCLUSION: The present retrospective chart review
      suggests that atypical antipsychotics may be effective and safe for the treatment
      of patients with PBD. In particular, treatment with aripiprazole may be more
      effective than treatment with other atypical antipsychotics in the early phase.
      These results should be verified in future multi-center controlled studies.

PMID- 24023552
TI  - The prevalence of metabolic syndrome in schizophrenic patients using
      antipsychotics.
AB  - OBJECTIVE: To examine the prevalence of metabolic syndrome and its risk factors
      in a large group of schizophrenic patients. METHODS: Sociodemographic and
      treatment data were collected from medical records of 1,103 inpatients and
      outpatients treated for schizophrenia at Seoul National Hospital in Seoul, Korea.
      Anthropometric measurement and blood testing were conducted for collection of
      physical and biochemical data and diagnosis of metabolic syndrome. Data for
      metabolic syndrome prevalence were compared by sex, age, metabolic syndrome
      markers present, treatment of markers, and types of antipsychotics and individual
      drug agents used. RESULTS: Mean prevalence of metabolic syndrome in all subjects
      was 43.9% and 40.1% according to adapted Adult Treatment Panel III (ATP-IIIa) and
      International Diabetes Federation criteria, respectively. No significant
      differences were found in prevalence according to ATP-IIIa criteria between men
      (42.6%) and woman (45.9%). A trend toward higher prevalence with age was observed
      for both sexes until 50 years, followed by a continued increase for women but a
      decrease for men. Use of a combination of atypical antipsychotics was associated
      with the highest metabolic syndrome prevalence and use of aripiprazole with the
      lowest. High percentages of subjects with hypertension and dyslipidemia were not
      being treated for these conditions. CONCLUSION: Despite their higher prevalence
      in schizophrenic patients, metabolic syndrome and its markers are not being
      adequately managed in these patients. Treatment of schizophrenic patients
      requires attention to not only their psychiatric conditions but also associated
      medical conditions by individual health care practitioners and hospitals as well
      as the public health care sector as a whole.

PMID- 24023553
TI  - Association between Alcoholism Family History and Alcohol Screening Scores among
      Alcohol-dependent Patients.
AB  - OBJECTIVE: Several tests can be used to screen for alcohol dependence (AD), a
      prevalent disease with a heterogeneous etiology. As some patients with AD have a
      strong familial tendency in this regard, a family history of alcohol use
      disorders can affect the outcomes of screening tests and diagnostic evaluations
      for AD. In this study, we evaluated associations between a family history of
      alcohol use disorders and evaluations using the Cut down, Annoyed, Guilty, Eye
      opener (CAGE) test, Alcohol Use Disorder Identification Test (AUDIT), and
      Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV)
      diagnostic criteria among patients with AD. METHODS: We recruited 487 male
      patients with AD from eight hospitals in Korea. Patients were evaluated using the
      CAGE, AUDIT, and DSM-IV diagnostic criteria. Patients with and without family
      histories were compared in terms of these assessment tools. RESULTS: Drinking
      initiation, uncontrollable drinking, and problem drinking occurred earlier and
      CAGE "annoyed" scores were higher in patients with a family history. Alcohol
      problems before the age of 25 years, frequency of spontaneous or compulsive
      alcohol-seeking behavior, and frequencies of psychological dependence and guilt
      related to alcohol use were also higher. CONCLUSION: Earlier drinking problems,
      higher scores on specific items of the CAGE, and AUDIT, and meeting more
      diagnostic criteria indicate more dependent, harmful drinking by patients with AD
      who have a family history of this condition. Clinicians should consider patients'
      family history of alcohol use disorders when screening for AD to identify the
      correct diagnosis and develop appropriate treatment plans for these patients.

PMID- 24023554
TI  - Low-frequency, Repetitive Transcranial Magnetic Stimulation for the Treatment of
      Patients with Posttraumatic Stress Disorder: a Double-blind, Sham-controlled
      Study.
AB  - OBJECTIVE: Several studies have suggested that repetitive transcranial magnetic
      stimulation (rTMS) of the right prefrontal cortex may be useful in the treatment
      of posttraumatic stress disorder (PTSD). The aim of this study was to compare the
      effect of rTMS on the right prefrontal cortex with that of sham stimulation among
      patients with PTSD. METHODS: In total, 18 patients with PTSD were randomly
      assigned to the 1-Hz low-frequency rTMS group or the sham group for 3 weeks.
      Primary efficacy measures were the Clinician-Administered PTSD Scale (CAPS) and
      its subscales, assessed at baseline and at 2, 4, and 8 weeks. RESULTS: All CAPS
      scores improved significantly over the study period. We found significant
      differences in the re-experiencing scores (F=7.47, p=0.004) and total scores
      (F=6.45, p=0.008) on the CAPS. The CAPS avoidance scores showed a trend toward
      significance (F=2.74, p=0.055), but no significant differences in the CAPS
      hyperarousal scores were observed. CONCLUSION: The present study showed low
      frequency rTMS to be an effective and tolerable option for the treatment of PTSD.
      Trials using variable indices of rTMS to the right prefrontal cortex and
      explorations of the differences in the effects on specific symptom clusters may
      be promising avenues of research regarding the use of rTMS for PTSD.

PMID- 24023555
TI  - Eosinophilia, pleural effusion, hepatitis, and jaundice occurring early in
      clozapine treatment.
AB  - Clozapine use is associated with various adverse events, some of which have
      received little attention, including eosinophilia, pleural effusion, and
      hepatitis. Because of the fatality of jaundice with hepatitis, it is necessary to
      understand the course and management of clozapine-induced eosinophilia and
      hepatitis. We report on a case in which the eosinophil count began to increase
      shortly after clozapine use, and pleural effusion and fever then developed at the
      time eosinophilia was at its peak level. Jaundice with hepatitis consecutively
      developed when all the above symptoms subsided. The liver function recovered
      rapidly after clozapine was discontinued. We recommend that patients who develop
      rapid eosinophilia at the beginning of clozapine treatment should be monitored
      with LFTs, chest X-rays, and urine analysis tests. 

PMID- 24023556
TI  - Interstitial lung diseases: respiratory review of 2013.
AB  - Interstitial lung diseases are heterogeneous entities with diverse clinical
      presentations. Among them, idiopathic pulmonary fibrosis and connective tissue
      disease-associated interstitial lung disease are specific categories that
      pulmonologists are most likely to encounter in the clinical field. Despite the
      accumulated data from extensive clinical trial and observations, we continue to
      have many issues which need to be resolved in this field. In this update, we
      present the review of several articles regarding the clinical presentation,
      prognosis and treatment of patients with idiopathic pulmonary fibrosis or
      connective tissue disease-associated interstitial lung disease. 

PMID- 24023557
TI  - Clinical features and prognostic factors in elderly koreans with advanced non
      small-cell lung cancer in a tertiary referral hospital.
AB  - BACKGROUND: More than half of cases for advanced non-small-cell lung cancer
      (NSCLC) occur in elderly patients with a median age at diagnosis of 70 years. The
      aim of our study was to examine the clinical features and prognostic factors
      contributing to mortality in elderly patients with advanced NSCLC. METHODS:
      Following a retrospective review of clinical data, 122 patients aged 70 years and
      over with a histopathological diagnosis of locally advanced (stage IIIB, n=32)
      and metastatic (stage IV, n=90) NSCLC between 2005 and 2011 were enrolled.
      RESULTS: The median age was 76 years (interquartile range, [IQR], 72-80 years),
      and 85 (70%) patients were male. Fifty-seven (46%) patients had never smoked, and
      17 (19%) were in a malnourished state with a body mass index (BMI) of <18.5
      kg/m(2). The initial treatments included chemotherapy (40%) and radiotherapy
      (7%), but 57% of the patients received supportive care only. The 1-year survival
      rate was 32%, and the 3-year survival rate was 4%, with a median survival
      duration of 6.2 months (IQR, 2.5-15.3 months). Male gender (hazard ratio [HR],
      2.2; 95% confidence interval [CI], 1.3-3.9; p=0.005), low BMI (HR, 2.3; 95% CI,
      1.3-3.9; p=0.004), and supportive care only (HR, 1.9; 95% CI, 1.2-2.9; p=0.007)
      were independent predictors of shorter survival based on a Cox proportional
      hazards model. CONCLUSION: Elderly patients with advanced NSCLC had a poor
      prognosis, particularly male patients, those with a low BMI, and those who
      received supportive care only.

PMID- 24023558
TI  - Elevated prx1 provides resistance to docetaxel, but is not associated with
      predictive significance in lung cancer.
AB  - BACKGROUND: This study was conducted in order to elucidate the effects of
      docetaxel on the growth of peroxiredoxin 1 (Prx1) knockdown A549 xenograft tumors
      and further tested the role of Prx1 as a predictor for how a patient would
      respond to docetaxel treatment. METHODS: Effects of docetaxel on the growth of
      scrambled- and shPrx1-infected A549 xenograft tumors in nude mice were measured.
      Moreover, immunohistochemical expression of Prx1 was evaluated in paraffin
      embedded tissues from 24 non-small cell lung cancer patients who had received
      docetaxel-cisplatin regimens as a first-line treatment. RESULTS: Docetaxel
      treatment in Prx1 knockdown xenograft tumor resulted in reduced tumors growth
      compared with other groups. Prx1 knockdown increased the production of cleaved
      caspases-8 and -9 in the control itself compared to scramble tumors. Moreover,
      docetaxel treatment in Prx1 knockdown tissue led to an increased protein band.
      Phosphorylated Akt was found in Prx1 scramble tissues. Phosphorylated FOXO1 was
      detected in the docetaxel treatment group. On the other hand, Prx1 knockdown
      completely suppressed the Akt-FOXO1 axis. The median progression-free survival
      (PFS) of patients with low Prx1 expression was 7 months (95% confidence interval
      [CI], 6.0-7.7), whereas the median progression-free survival of patients with
      high Prx1 expression was 4 months (95% CI, 4.0-5.0). However, high Prx1
      expression was not associated with decreased PFS (p=0.114). CONCLUSION: Our
      findings suggest that elevated Prx1 provides resistance to docetaxel treatment
      through suppression of FOXO1-induced apoptosis in A549 xenograft tumors, but may
      not be related with the predictive significance for response to docetaxel
      treatment.

PMID- 24023559
TI  - Minute pulmonary meningothelial-like nodules simulating hematogenous lung
      metastasis: a case report.
AB  - A 52-year-old man was referred to our clinic for an 11.3 mm nodule in the left
      lower lobe that was discovered on a chest computed tomography (CT) scan. Eleven
      small nodules were subsequently found in both lungs. Initially, we performed a
      transthoracic needle aspiration using CT scan guidance. The pathologic report
      showed a few clusters of atypical cells that were suspicious for malignancy. The
      positron emission tomography images revealed multiple lung nodules scattered
      throughout both lungs. The largest nodule (11.3 mm) in the left lower lobe did
      not have any discernible fludeoxyglucose uptake. For pathologic confirmation, we
      consulted a thoracic surgeon to perform the video-assisted thoracoscopic surgery.
      The final diagnosis was minute pulmonary meningothelial-like nodules (MPMNs).
      MPMNs are benign in nature, and only a few cases require treatment. However, when
      clinicians are suspicious of potential malignancy, a pathological correlation is
      essential, even if the final diagnosis is MPMNs. 

PMID- 24023560
TI  - A case of giant, benign schwannoma associated with total lung collapse by bloody
      effusion.
AB  - Benign schwannoma is the most common neurogenic tumor in the mediastinum.
      Mediastinal benign schwannomas are most often asymptomatic and rarely accompanied
      by bloody pleural effusion. In the clinical analysis of 7 cases of pulmonary
      schwannomas, pleural effusion, and blood invasion were evident in 3 patients with
      malignant schwannoma. Herein, we report a rare case of giant, benign schwannoma
      presented with total collapse of right lung by massive, bloody pleural effusion. 

PMID- 24023561
TI  - Community-Acquired Necrotizing Pneumonia Caused by ST72-SCCmec Type IV
      Methicillin-Resistant Staphylococcus aureus in Korea.
AB  - Methcillin-resistant Staphylococcus aureus (MRSA) has emerged as an important
      cause of community-acquired infections, which has been recently designated as
      community-associated (CA) MRSA. Panton-Valentine leukocidin (PVL)-negative
      multilocus sequence type 72 (ST72)-staphylococcal cassette chromosome mec
      (SCCmec) type IV has been reported as the predominat CA-MRSA strain in Korea and
      is commonly associated with skin and soft tissue infections in addition to
      healthcare-associated pneumonia. However, community-acquired pneumonia (CAP) for
      this strain has not yet been reported. We hereby report two cases of CAP caused
      by PVL-negative ST72-SCCmec type IV strain in patients who had no risk factors
      for MRSA acquisition. While CA-MRSA infections are not yet prevalent in Korea,
      our cases suggest that CA-MRSA should be considered in cases of severe CAP,
      especially for cases associated with necrotizing pneumonia. 

PMID- 24023562
TI  - Tracheal stenosis after tracheostomy treated successfully with papillotome
      electrocautery.
AB  - A 39-year-old woman presented with symptoms of dyspnea. Ten years previously, she
      had received a tracheostomy because of the decision to not continue taking an
      anticonvulsant drug. Presently, chest computed tomography showed diffuse stenosis
      and focal web at the cervical trachea. We performed bronchoscopy and found a two
      thirds reduction of the upper trachea due to the web-like fibrotic stenosis.
      Papillotome electrocautery removed the stenotic lesion. Endobronchial
      electrocautery is a valuable tool with potential for therapy of an endobronchial
      obstructing airway lesion. We report this case to introduce the successful
      treatment with papillotome electrocautery. 

PMID- 24023563
TI  - NFAT signaling in osteoblasts regulates the hematopoietic niche in the bone
      microenvironment.
AB  - Osteoblasts support hematopoietic cell development, including B lymphopoiesis. We
      have previously shown that the nuclear factor of activated T cells (NFAT)
      negatively regulates osteoblast differentiation and bone formation.
      Interestingly, in smooth muscle, NFAT has been shown to regulate the expression
      of vascular cellular adhesion molecule-1 (VCAM-1), a mediator of cell adhesion
      and signaling during leukocyte development. To examine whether NFAT signaling in
      osteoblasts regulates hematopoietic development in vivo, we generated a mouse
      model expressing dominant-negative NFAT driven by the 2.3 kb fragment of the
      collagen-alphaI promoter to disrupt NFAT activity in osteoblasts (dnNFAT(OB)).
      Bone histomorphometry showed that dnNFAT(OB) mice have significant increases in
      bone volume (44%) and mineral apposition rate (131%) and decreased trabecular
      thickness (18%). In the bone microenvironment, dnNFAT(OB) mice displayed a
      significant increase (87%) in Lineage(-)cKit(+)Sca-1(+) (LSK) cells and
      significant decreases in B220(+)CD19(-)IgM(-) pre-pro-B cells (41%) and
      B220(+)CD19(+)IgM(+) immature B cells (40%). Concurrent with these findings, LSK
      cell differentiation into B220(+) cells was inhibited when cocultured on
      differentiated primary osteoblasts harvested from dnNFAT(OB) mice. Gene
      expression and protein levels of VCAM-1 in osteoblasts decreased in dnNFAT(OB)
      mice compared to controls. These data suggest that osteoblast-specific NFAT
      activity mediates early B lymphopoiesis, possibly by regulating VCAM-1 expression
      on osteoblasts.

PMID- 24023564
TI  - Role of Th17 cells in skin inflammation of allergic contact dermatitis.
AB  - Extending the classical concept considering an imbalance exclusively of T
      helper(h) 1 and Th2 cells on the bottom of many inflammatory diseases, Th17 cells
      were recently described. Today, there is sufficient experimental evidence to
      classify psoriasis and allergic contact dermatitis (ACD) amongst other
      inflammatory skin disorders as IL-17 associated diseases. In several human
      studies, T-cell-clones could be isolated from eczema biopsies, and high IL-17
      levels were observed after challenge with allergen. In the last years, the
      phenotype of these IL-17 releasing T cells was in the focus of discussion. It has
      been suggested that Th17 could be identified by expression of retinoic acid
      receptor-related orphan receptor (ROR)C (humans) or RORgammat (mice) and IL-17,
      accompanied by the absence of IFN-gamma and IL-22. In cells from skin biopsies,
      contact allergens elevate IL-17A, IL-23, and RORC within the subset of Th cells.
      The indications for a participation of Th17 in the development of ACD are
      supported by data from IL-17 deficient mice with reduced contact hypersensitivity
      (CHS) reactions that could be restored after transplantation of wild type CD4(+)
      T cells. In addition to Th17 cells, subpopulations of CD8(+) T cells and
      regulatory T cells are further sources of IL-17 that play important roles in ACD
      as well. Finally, the results from Th17 cell research allow today identification
      of different skin diseases by a specific profile of signature cytokines from Th
      cells that can be used as a future diagnostic tool.

PMID- 24023565
TI  - Cytomegalovirus in the neonate: immune correlates of infection and protection.
AB  - Fetal and neonatal infections caused by human cytomegalovirus (CMV) are important
      causes of morbidity and occasional mortality. Development of a vaccine against
      congenital CMV infection is a major public health priority. Vaccine design is
      currently focused on strategies that aim to elicit neutralizing antibody and T
      cell responses, toward the goal of preventing primary or recurrent infection in
      women of child-bearing age. However, there has been relatively little attention
      given to understanding the mechanisms of immune protection against acquisition of
      CMV infection in the fetus and newborn and how this information might be
      exploited for vaccine design. There has similarly been an insufficient study of
      what deficits in the immune response to CMV, both for mother and fetus, may
      increase susceptibility to congenital infection and disease. Protection of the
      fetus against vertical transmission can likely be achieved by protection of the
      placenta, which has its own unique immunological milieu, further complicating the
      analysis of the correlates of protective immunity. In this review, the current
      state of knowledge about immune effectors of protection against CMV in the
      maternal, placental, and fetal compartments is reviewed. A better understanding
      of immune responses that prevent and/or predispose to infection will help in the
      development of novel vaccine strategies.

PMID- 24023567
TI  - Aberrant T helper 17 cells and related cytokines in bone marrow microenvironment
      of patients with acute myeloid leukemia.
AB  - In this study, we mainly investigate the role of Th17 cells, Th1 cells, and their
      related cytokines in the pathophysiology of AML. BM and PB were extracted from
      ND, CR, and relapsed-refractory AML patients and controls. Th subsets frequencies
      were examined by flow cytometry. BM plasma Th-associated cytokines levels were
      determined by ELISA. The frequencies of Th17 and Th1, and IFN-gamma or TGF-beta
      concentrations were significantly decreased in ND compared with CR patients or
      controls. Th17 percentage was significantly lower in BM than in PB for ND
      patients but was higher in BM for CR patients. However, in CR or relapsed
      refractory patients, Th1 percentage in BM was higher than that in PB. Moreover,
      BM IL-17A level showed a decreased trend in ND patients. A significant elevation
      of plasma IL-6 level was found in ND compared with CR patients or controls. IL
      17A showed the positive correlation with IL-6 concentration. And Th17 cells
      frequencies and TGF- beta1 concentration were increased in BM from AML patients
      achieving CR after chemotherapy. Moreover, a significant decrease of BM plasma
      TGF- beta1 level was found in M3 patients compared with the other subtypes. Our
      findings suggest that Th17 and related cytokines may be implicated in AML
      pathogenesis.

PMID- 24023566
TI  - The role of microglia and matrix metalloproteinases involvement in
      neuroinflammation and gliomas.
AB  - Matrix metalloproteinases (MMPs) are involved in the pathogenesis of
      neuroinflammatory diseases (such as multiple sclerosis) as well as in the
      expansion of malignant gliomas because they facilitate penetration of anatomical
      barriers (such as the glia limitans) and migration within the neuropil. This
      review elucidates pathomechanisms and summarizes the current knowledge of the
      involvement of MMPs in neuroinflammation and glioma, invasion highlighting
      microglia as major sources of MMPs. The induction of expression, suppression, and
      multiple pathways of function of MMPs in these scenarios will also be discussed.
      Understanding the induction and action of MMPs might provide valuable information
      and reveal attractive targets for future therapeutic strategies.

PMID- 24023569
TI  - Involvement of Potassium Channels in Vasorelaxant Effect Induced by Valeriana
      prionophylla Standl. in Rat Mesenteric Artery.
AB  - Assays in vitro and in vivo were performed on extract from roots and leaves from
      the Valeriana prionophylla Standl. (VPR and VPF, resp.). In phenylephrine (1  MU
      M) precontracted rings, VPR (0.01-300  MU g/mL) induced a concentration-dependent
      relaxation (maximum response (MR) = 75.4 +/- 4.0%, EC50 = 5.97 (3.8-9.3) MU g/mL,
      n = 6]); this effect was significantly modified after removal of the endothelium
      (EC50 = 39.6 (27.2-57.6) MU g/mL, P < 0.05). However, VPF-induced vasorelaxation
      was less effective compared to VPR. When rings were preincubated with L-NAME (100
      MU M) or indomethacin (10  MU M), the endothelium-dependent relaxation induced
      by VPR was significantly attenuated (MR = 20.9 +/- 2.3%, 34.2 +/- 2.9%, resp., P
      < 0.001). In rings denuded endothelium, precontracted with KCl (80 mM), or in
      preparations pretreated with KCl (20 mM) or tetraethylammonium (1 or 3 mM), the
      vasorelaxant activity of VPR was significantly attenuated (MR = 40.0 +/- 8.2, n =
      5; 50.5 +/- 6.0%; 49.3 +/- 6.4%; 46.8 +/- 6.2%; resp., P < 0.01). In contrast,
      neither glibenclamide (10  MU M), barium chloride (30  MU M), nor 4-aminopyridine
      (1 mM) affected VPR-induced relaxation. Taken together, these results demonstrate
      that hypotension induced by VPR seems to involve, at least in part, a vascular
      component. Furthermore, endothelium-independent relaxation induced by VPR
      involves K(+) channels activation, most likely due to BKCa channels, in the rat
      superior mesenteric artery. 

PMID- 24023568
TI  - Multivariate granger causality analysis of acupuncture effects in mild cognitive
      impairment patients: an FMRI study.
AB  - Evidence from clinical reports has indicated that acupuncture has a promising
      effect on mild cognitive impairment (MCI). However, it is still unknown that by
      what way acupuncture can modulate brain networks involving the MCI. In the
      current study, multivariate Granger causality analysis (mGCA) was adopted to
      compare the interregional effective connectivity of brain networks by varying
      needling depths (deep acupuncture, DA; superficial acupuncture, SA) and at
      different cognitive states, which were the MCI and healthy control (HC). Results
      from DA at KI3 in MCI showed that the dorsolateral prefrontal cortex and
      hippocampus emerged as central hubs and had significant causal influences with
      each other, but significant in HC for DA. Moreover, only several brain regions
      had remarkable causal interactions following SA in MCI and even few brain regions
      following SA in HC. Our results indicated that acupuncture at KI3 at different
      cognitive states and with varying needling depths may induce distinct
      reorganizations of effective connectivities of brain networks, and DA at KI3 in
      MCI can induce the strongest and more extensive effective connectivities related
      to the therapeutic effect of acupuncture in MCI. The study demonstrated the
      relatively functional specificity of acupuncture at KI3 in MCI, and needling
      depths play an important role in acupuncture treatments. 

PMID- 24023570
TI  - Systematic review of randomized clinical trials of acupressure therapy for
      primary dysmenorrhea.
AB  - The evidence of acupressure is limited in the management of dysmenorrhea. To
      evaluate the efficacy of acupressure in the treatment of primary dysmenorrhea
      based on randomized controlled trials (RCTs), we searched MEDLINE, the Chinese
      Biomedical Database (CBM), and the Cochrane Central Register of Controlled Trials
      (CENTRAL) databases from inception until March 2012. Two reviewers independently
      selected articles and extracted data. Statistical analysis was performed with
      RevMan 5.1 software. Eight RCTs were identified from the retrieved 224 relevant
      records. Acupressure improved pain measured with VAS (-1.41 cm 95% CI [-1.61, 
      1.21]), SF-MPQ at the 3-month followup (WMD -2.33, 95% CI [-4.11, -0.54]) and 6
      month followup (WMD -4.67, 95% CI [-7.30, -2.04]), and MDQ at the 3-month
      followup (WMD -2.31, 95% CI [-3.74, -0.87]) and 6-month followup (WMD -4.67, 95%
      CI [-7.30, -2.04]). All trials did not report adverse events. These results were
      limited by the methodological flaws of trials. 

PMID- 24023571
TI  - Effects of Swedish massage therapy on blood pressure, heart rate, and
      inflammatory markers in hypertensive women.
AB  - Swedish Massage Therapy (SMT) is known for its therapeutic relaxation effects.
      Hypertension is associated with stress and elevated endothelial inflammatory
      markers. This randomized control trial measured the effects of whole body SMT
      (massage group) or resting (control group) an hour weekly for four weeks on
      hypertensive women. Blood pressure (BP) and heart rate (HR) were measured before
      and after each intervention and endothelial inflammatory markers: vascular
      endothelial adhesion molecules 1 (VCAM-1) and intracellular adhesion molecules 1
      (ICAM-1) were measured at baseline and after the last intervention. Massage group
      (n=8) showed significant systolic BP (SBP) reduction of 12 mmHg (P=0.01) and
      diastolic BP (DBP) reduction of 5 mmHg (P=0.01) after four sessions with no
      significant difference between groups. Reductions in HR were also seen in massage
      group after sessions 1, 3, and 4 with significant difference between groups. VCAM
      1 showed significant reduction after four sessions: the massage group showed
      reduction of 998.05 ng/mL (P=0.03) and the control group of 375.70 ng/mL (P=0.01)
      with no significant differences between groups. There were no changes in ICAM-1.
      In conclusion, SMT or resting an hour weekly has effects on reducing BP, HR, and
      VCAM-1 in hypertensive women. 

PMID- 24023573
TI  - ITIH4: A New Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease
      Patient Identified with Proteomic Method.
AB  - Objective. This trial aims to look for the protein biomarker of "toxin syndrome"
      of CHD patients. Methods. We have performed two trials in this paper. The first
      trial was a randomized controlled trial (RCT) of the plasma proteome in unstable
      angina (UA) patients by Maldi-Tof Mass. The second trial was a nested case
      control study in 1503 stable CHD patients with one-year followup for acute
      cardiovascular events (ACEs). Results. In the RCT study, 12 protein spots were
      found to be the differential protein for the significant differences between the
      difference of before and after treatment in group A and group B; 2 of them
      (3207.37 Da and 4279.95 Da) was considered to be unique to "toxin syndrome" for
      being differential proteins of group B but not group A. These 2 spots were
      identified as Isoform 1 of Fibrinogen alpha chain precursor (FGA, 3207.37 Da) and
      Isoform 2 of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4, 4279.95 Da),
      respectively. In the nested case-control study, the result of Western blot
      demonstrated that protein expression of ITIH4 in the group with followup ACEs was
      significantly lower than the matched group without followup ACEs (P = 0.027).
      Conclusion. ITIH4 might be a new potential biomarker of CHD "toxin syndrome" in
      TCM, indicating the potential role in early identifying high-risk CHD patients in
      stable period. 

PMID- 24023572
TI  - Spiritual therapy to improve the spiritual well-being of Iranian women with
      breast cancer: a randomized controlled trial.
AB  - Purpose. The aim of this study was to investigate the role of spiritual therapy
      intervention in improving the spiritual well-being and quality of life (QOL) of
      Iranian women with breast cancer. Methods. This randomized controlled clinical
      trial (RCT) recruited 65 women with breast cancer, randomly assigned to a 6-week
      spirituality-based intervention (n = 34) or control group (n = 31). Before and
      after six-week spiritual therapy intervention, spiritual well-being and quality
      of life (QOL) were assessed using Functional Assessment of Chronic Illness
      Therapy Spiritual Well-being scale (FACIT-Sp12) and cancer quality-of-life
      questionnaire (QLQ-C30), respectively. t-test, Paired t-test, pearson's
      correlation, and hierarchical regression analyses were used for analysis using
      Predictive Analytic software (PASW, version 18) for Windows. Results. After six
      spiritual therapy sessions, the mean spiritual well-being score from 29.76 (SD =
      6.63) to 37.24 (SD = 3.52) in the intervention group (P < 0.001). There was a
      significant difference between arms of study (F = 22.91, P < 0.001). A
      significant positive correlation was detected between meaning and peace with all
      subscales of functional subscales on European Organization for Research and
      Treatment of Cancer quality of Life (EORTC QLQ-C30) (P < 0.05). Hierarchical
      regression analyses of participants indicated that the study arm, pain, and
      financial impact were significant predictors of spiritual well-being and overall
      QOL. Social functioning was another significant predictor of spiritual well
      being. Conclusion. The results of this randomized controlled trial study suggest
      that participation in spiritual therapy program is associated with improvements
      in spiritual well-being and QOL. Targeted interventions to acknowledge and
      incorporate spiritual needs into conventional treatment should be considered in
      caring of Iranian patients with breast cancer. 

PMID- 24023574
TI  - Autonomic conditions in tinnitus and implications for korean medicine.
AB  - Tinnitus patients suffer from not only auditory sensations but also physical,
      mental, and social difficulties. Even though tinnitus is believed to be
      associated with the autonomic nervous system, changes in autonomic conditions in
      tinnitus patients are not receiving much research attention. The aims of this
      study were to investigate the autonomic condition of tinnitus patients and to
      consider Korean medicine in the treatment of tinnitus with an evidence-based
      approach. We performed a retrospective chart review and compared the heart rate
      variability (HRV) parameters of 40 tinnitus patients (19 acute and 21 chronic)
      and 40 healthy controls. In tinnitus patients, the power of the high frequency
      component and total power of the HRV significantly decreased (P < 0.05), and the
      low frequency to high frequency ratio significantly increased (P < 0.05). There
      was no significant difference between the acute and chronic patients. When
      comparing each group with the controls, there was a tendency that the longer the
      duration of tinnitus was, the larger the observed HRV change was. In conclusion,
      tinnitus patients have vagal withdrawal and sympathetic overactivity, and chronic
      tinnitus more strongly affects autonomic conditions than acute tinnitus. This
      study provides evidence for Korean medical treatments of tinnitus, such as
      acupuncture and Qi-training, that cause modulation of cardiac autonomic function.

PMID- 24023575
TI  - Integrative Western and chinese medicine on coronary heart disease: where is the
      orientation?
AB  - Coronary heart disease (CHD) is the leading cause of death. As the main treatment
      of CHD, modern medicine has improved dramatically in recent years. Although
      researches of TCM and integrative medicine on CHD are witnessed encouraging
      progress in many respects, the role TCM playing in the prevention and treatment
      of CHD has been unprecedentedly challenged under such circumstance of the very
      fast development of modern medicine. In order to share mutual complementary
      advantages of TCM and western medicine, this review summarizes the relatively
      prominent researches of TCM and integrative medicine on CHD in recent years, and
      illuminates the issue of the orientation of the further research of integrative
      medicine on CHD, including (1) original innovation of TCM etiology and
      pathogenesis, (2) combination of disease and TCM syndrome, (3) biological basis
      of TCM syndrome of CHD, (4) clinical design and quality control of integrative
      medicine research, (5) herb-drug interaction, (6) difficulties and hot issues of
      modern medicine. 

PMID- 24023576
TI  - Evidence for the Primo Vascular System above the Epicardia of Rat Hearts.
AB  - We for the first time reported evidence for the existence of a novel network, a
      PVS, abovethe epicardium of the rat heart. (1) We were consecutively able to
      visualize the PVs and the PNs above the epicardial spaces of five rats' hearts by
      using Cr-Hx spraying or injection. (2) Hematoxylin and eosin (H&E) and toluidine
      blue staining of the PVs and the PNs showed that they consisted of a basophilic
      matrix; specifically the PNs contained several mast cells, some of which were
      degranulating into pericardial space. Also, 4', 6-diamidino-2 phenylindole (DAPI)
      images of the PVs and the PNs showed that they contained various kinds of cells.
      (3) Transmission electron microscopic (TEM) longitudinal image of the PVs showed
      that the sinuses contained many granules with high-electron-density cores in
      parallel with putative endothelial cells. (4) TEM images of the PNs demonstrated
      that they consisted of lumen-containing cells surrounded by fibers and that they
      had mast cells that were degranulating toward the epicardium of the rat heart.
      The above data suggest that mast-cells-containing novel network exists above the
      epicardium of the rat heart. 

PMID- 24023578
TI  - Specific Link between Lung and Large Intestine: A New Perspective on Neuropeptide
      Secretion in Lung with Herbal Laxative Stimulation.
AB  - Background. To investigate the specific link between lung and large intestine.
      Methods. Rat COPD-like model was prepared. Mirabilite or Chinese rhubarb was
      administrated intragastrically to stimulate the large intestine. Histological
      analysis of lung inflammation was assessed. The tissues levels of SP, VIP, NK1R,
      VIPR1, and VIPR2 were measured by using ELISA kits. In addition, mouse model of
      allergic asthma was prepared. Mirabilite was administrated intragastrically to
      stimulate the large intestine. Airway responsiveness and lung inflammation were
      assessed. The tissues levels of SP, VIP, NKA, NKB, NK1R, VIPR1, and VIPR2 were
      measured by using ELISA kits. Results. Stimulating the intestine with Mangxiao or
      Dahuang, SP, NK-1R, VIP, VIPR1, and VIPR2 were significantly increased in
      intestine tissues of rats with COPD and mice with asthma. Meanwhile, the SP and
      NK1R were significantly decreased, while VIP, VIPR1, and VIPR2 were significantly
      increased in lung tissues. An abnormal secretion of SP and VIP can be observed in
      other tissues; however, no marked changes were found in the receptors. The NKA
      and NKB levels were similar in lung tissues of mice with asthma among groups.
      Conclusions. Stimulating intestine with Mangxiao or Dahuang can specifically
      regulate the secretion of SP, VIP, and the receptors in lung tissues. 

PMID- 24023577
TI  - Acupuncture and clomiphene citrate for live birth in polycystic ovary syndrome:
      study design of a randomized controlled trial.
AB  - Acupuncture is an alternative therapy to induce ovulation in women with
      polycystic ovary syndrome (PCOS), but there is no study reporting the live birth
      rate following ovulation induction by acupuncture or its potential as an adjuvant
      treatment to clomiphene citrate (CC). We assess the efficacy of acupuncture with
      or without CC in achieving live births among 1000 PCOS women in Mainland China.
      This paper reports the methodology of an ongoing multicenter randomized
      controlled trial. The randomization scheme is coordinated through the central
      mechanism and stratified by the participating sites. Participants will be
      randomized into one of the four treatment arms: (A) true acupuncture and CC, (B)
      control acupuncture and CC, (C) true acupuncture and placebo CC, and (D) control
      acupuncture and placebo CC. To ensure the quality and integrity of the trial we
      have developed a unique multinational team of investigators and Data and Safety
      Monitoring Board. Up to the end of April 2013, 326 subjects were recruited. In
      conclusion, the success of this trial will allow us to evaluate the additional
      benefit of acupuncture beyond the first line medicine for fertility treatment in
      PCOS women in an unbiased manner. 

PMID- 24023579
TI  - Behavioral and neurochemical effects of alpha-lipoic Acid in the model of
      Parkinson's disease induced by unilateral stereotaxic injection of 6-ohda in rat.
AB  - This study aimed to investigate behavioral and neurochemical effects of alpha 
      lipoic acid (100 mg/kg or 200 mg/kg) alone or associated with L-DOPA using an
      animal model of Parkinson's disease induced by stereotaxic injection of 6
      hydroxydopamine (6-OHDA) in rat striatum. Motor behavior was assessed by
      monitoring body rotations induced by apomorphine, open field test and cylinder
      test. Oxidative stress was accessed by determination of lipid peroxidation using
      the TBARS method, concentration of nitrite and evaluation of catalase activity.
      alpha -Lipoic acid decreased body rotations induced by apomorphine, as well as
      caused an improvement in motor performance by increasing locomotor activity in
      the open field test and use of contralateral paw (in the opposite side of the
      lesion produced by 6-OHDA) at cylinder test. alpha -lipoic acid showed
      antioxidant effects, decreasing lipid peroxidation and nitrite levels and
      interacting with antioxidant system by decreasing of endogenous catalase
      activity. Therefore, alpha -lipoic acid prevented the damage induced by 6-OHDA or
      by chronic use of L-DOPA in dopaminergic neurons, suggesting that alpha -lipoic
      could be a new therapeutic target for Parkinson's disease prevention and
      treatment. 

PMID- 24023580
TI  - Studies on chromatographic fingerprint and fingerprinting profile-efficacy
      relationship of polygoni perfoliati herba.
AB  - Polygoni Perfoliati Herba is widely used in China with antibacterium, anti
      inflammatory, expectorant, antitumor, and antivirus activities. To reveal the
      mechanisms of the activities of Polygoni Perfoliati Herba, the relationship
      between the fingerprinting profile and its bioactivities was investigated. In the
      present study, high-performance liquid chromatographic (HPLC) fingerprinting
      method was developed. The established method was applied to analyze 51 batches of
      Polygoni Perfoliati Herba samples collected from different locations or in
      different harvesting times in China. Chemometrics, including similarity analysis,
      hierarchical clustering analysis, and principal component analysis, were used to
      express their similarities. It was found that similarity values of the samples
      were in the range of 0.432-0.998. The results of analgesic tests indicated that
      Polygoni Perfoliati Herba could significantly inhibit pain induced by hot plate
      and acetic acid in mice. The results of anti-inflammatory tests showed that
      Polygoni Perfoliati Herba had good anti-inflammatory effects (P < 0.01) in two
      models including dimethyl benzene-induced ear edema and acetic acid-induced
      peritoneal permeability in mice. Combining the results from chromatographic
      fingerprints with those from bioactivities, we found that seven peaks from
      Polygoni Perfoliati Herba were mainly responsible for analgesic and anti
      inflammatory activities. 

PMID- 24023581
TI  - Proanthocyanidin Attenuation of Oxidative Stress and NF- kappa B Protects
      Apolipoprotein E-Deficient Mice against Diabetic Nephropathy.
AB  - Hyperlipidemia and hyperglycemia result in oxidative stress and play a major role
      in the development of diabetic nephropathy (DN). We explored the effects of
      proanthocyanidin (PA) on the induction and progression of DN in apolipoprotein E
      deficient mice. Diabetes Mellitus was induced in ten-week-old male apoE(-/-)mice
      using streptozotocin (STZ). Mice were fed with a high-fat diet in presence or
      absence of PA. PA treatment significantly reduced the high cholesterol levels,
      restored renal functions, and reduced albuminuria in the PA-treated diabetic mice
      compared with the diabetic untreated mice. In addition, the glomerular mesangial
      expansion in the diabetic mice was attenuated as a result of PA supplementation.
      Moreover, PA treatment restored the elevated levels of MDA and CML and the
      reduced activity of SOD and GSH in the diabetic mice. Furthermore, PA feeding
      reduced the activation and translocation of NF- kappa B to the nucleus compared
      with the diabetic untreated animals. Reduction of NF- kappa B activation resulted
      in the attenuation of the expression of IL-6, TGF beta , and RAGE which protected
      PA-treated mice against DN. The renoprotective effects of PA were found to be
      time independent regardless of whether the dietary feeding with PA was started
      pre-, co-, or post-STZ injection. In conclusion, part of the beneficial effects
      of PA includes the disruption of the detrimental AGE-RAGE-NF kappa B pathways. 

PMID- 24023582
TI  - Observation on pain release by long-round needle therapy in knee osteoarthritis
      related with meridian-sinews theory.
AB  - To evaluate the effectiveness of long-round needle therapy for pain relief in
      patients with knee osteoarthritis, 192 patients were included in a multicenter,
      randomized, controlled trial. 97 patients were randomized to the long-round
      needle therapy group (EG), and 95 patients were randomized to the control group
      (CG). In EG, the long-round needle therapy was performed once every 7 days for 3
      therapy sessions. Ibuprofen sustained-release capsules were administered orally
      in CG, 1 pill each time, twice daily for 3 weeks. Curative effect was measured
      after the therapy and was evaluated at a 3-month follow-up interview. In EG, the
      treatment resulted in a basic cure for 79 patients, was effective for 15
      patients, and was ineffective for 1 patient. In CG, the treatment resulted in a
      basic cure for 30 patients, was effective for 38 patients, and was ineffective
      for 21 patients. In the follow-up examination in EG, 75 patients were basically
      cured, and the treatment was effective for 11 patients and ineffective for 9. In
      CG, 22 were basically cured, 31 found the treatment effective, and 36 found the
      treatment ineffective. The curative effects in EG after both the treatment and
      the 3-mouth followup were significantly more superior than that in CG (P < 0.01)
      which should be adopted more widely. 

PMID- 24023583
TI  - Clearance of free silica in rat lungs by spraying with chinese herbal kombucha.
AB  - The effects of spraying with kombucha and Chinese herbal kombucha were compared
      with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg)
      was injected into the lungs of rats, which were then treated with one of the
      experimental treatments for a month. The rats were then killed and the effects of
      the treatments were evaluated by examining the extent and severity of the
      histopathological lesions in the animals' lungs, measuring their organ
      coefficients and lung collagen contents, determining the dry and wet weights of
      their lungs, and measuring the free silica content of the dried lungs. In
      addition, lavage was performed on whole lungs taken from selected rats, and the
      numbers and types of cells in the lavage fluid were counted. The most effective
      treatment in terms of the ability to reduce lung collagen content and minimize
      the formation of pulmonary histopathological lesions was tetrandrine treatment,
      followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the
      lavage fluid cell counts indicated that tetrandrine treatment had severe adverse
      effects on macrophage viability. This effect was much less pronounced for the
      kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels
      in the lungs of animals treated with Chinese herbal kombucha were significantly
      lower than those for any other silica-exposed group. These preliminary results
      indicate that spraying with Chinese herbal kombucha preparations can effectively
      promote the discharge of silica dust from lung tissues. Chinese herbal kombucha
      inhalation may thus be a useful new treatment for silicosis and other
      pneumoconiosis diseases. 

PMID- 24023584
TI  - Interaction of carbamazepine with herbs, dietary supplements, and food: a
      systematic review.
AB  - Background. Carbamazepine (CBZ) is a first-line antiepileptic drug which may be
      prone to drug interactions. Systematic review of herb- and food-drug interactions
      on CBZ is warranted to provide guidance for medical professionals when
      prescribing CBZ. Method. A systematic review was conducted on six English
      databases and four Chinese databases. Results. 196 out of 3179 articles fulfilled
      inclusion criteria, of which 74 articles were reviewed and 33 herbal
      products/dietary supplement/food interacting with CBZ were identified. No fatal
      or severe interactions were documented. The majority of the interactions were
      pharmacokinetic-based (80%). Traditional Chinese medicine accounted for most of
      the interactions (n = 17), followed by food (n = 10), dietary supplements (n =
      3), and other herbs/botanicals (n = 3). Coadministration of 11 and 12 of the
      studied herbal products/dietary supplement/food significantly decreased or
      increased the plasma concentrations of CBZ. Regarding pharmacodynamic
      interaction, Xiao-yao-san, melatonin, and alcohol increased the side effects of
      CBZ while caffeine lowered the antiepileptic efficacy of CBZ. Conclusion. This
      review provides a comprehensive summary of the documented interactions between
      CBZ and herbal products/food/dietary supplements which assists healthcare
      professionals to identify potential herb-drug and food-drug interactions, thereby
      preventing potential adverse events and improving patients' therapeutic outcomes
      when prescribing CBZ. 

PMID- 24023585
TI  - Oral Panax notoginseng Preparation for Coronary Heart Disease: A Systematic
      Review of Randomized Controlled Trials.
AB  - This systematic review aims to evaluate current evidence for the benefit and side
      effect of oral Panax notoginseng preparation for coronary heart disease (CHD). We
      included 17 randomized clinical trials (17 papers and 1747 participants).
      Comparing with no intervention on the basis of conventional therapy, oral Panax
      notoginseng did not show significant effect on reducing cardiovascular events,
      but it could alleviate angina pectoris (including improving the symptoms of
      angina pectoris [RR 1.20; 95% CI 1.12 to 1.28; 7 trials, n = 791], improving
      electrocardiogram [RR 1.35; 95% CI 1.19 to 1.53; 8 trials, n = 727], decreasing
      the recurrence of angina pectoris [RR 0.38; 95% CI 0.16 to 0.94; 1 trials, n =
      60], duration of angina pectoris [RR -1.88; 95% CI -2.08 to -1.69; 2 trials, n =
      292], and dosage of nitroglycerin [MD -1.13; 95% CI -1.70 to -0.56; 2 trials, n =
      212]); oral Panax notoginseng had no significant difference compared with
      isosorbide dinitrate on immediate effect for angina pectoris [RR 0.96; 95% CI
      0.81 to 1.15; 1 trial, n = 80]. In conclusion, oral Panax notoginseng preparation
      could relieve angina pectoris related symptoms. However, the small sample size
      and potential bias of most trials influence the convincingness of this
      conclusion. More rigorous trials with high quality are needed to give high level
      of evidence, especially for the potential benefit of cardiovascular events. 

PMID- 24023586
TI  - CAM Use and Suggestions for Medical Care of Senior Citizens: A Qualitative Study
      Using the World Cafe Method.
AB  - Background. Little data exists concerning the reasons for using complementary and
      alternative (CAM) therapies by seniors. Therefore, the aim of this study is to
      learn about motives of German seniors for using CAM therapies and their wishes
      for health care in general. Methods. One focus group and one "World Cafe"
      following a semistructured interview guide were conducted. All discussions were
      recorded digitally, transcribed, and analyzed according to Qualitative Content
      Analysis using the software MAXQDA. Results. In total 21 seniors participated
      (eighteen female, three male, mean age 72.5 +/- 4.3 years). Most of the
      participants had lifelong experiences with medicinal herbs and home remedies due
      to unavailable conventional care during childhood. Also important for them were
      nutrition and exercise. These methods were often used as self-care to enhance
      wellbeing, to prevent and to cure illnesses. The participants would welcome an
      integration of CAM in health care services. They asked especially for more
      empathic physicians who are better trained in CAM and respect their experiences.
      Conclusion. The importance of life experience in regard to health care by senior
      can be seen as a resource. Qualitative studies investigating physician-patient
      relationships and intergenerational aspects in CAM use could be of interest for
      further studies. 

PMID- 24023588
TI  - Scale-specific multifractal medical image analysis.
AB  - Fractal geometry has been applied widely in the analysis of medical images to
      characterize the irregular complex tissue structures that do not lend themselves
      to straightforward analysis with traditional Euclidean geometry. In this study,
      we treat the nonfractal behaviour of medical images over large-scale ranges by
      considering their box-counting fractal dimension as a scale-dependent parameter
      rather than a single number. We describe this approach in the context of the more
      generalized Renyi entropy, in which we can also compute the information and
      correlation dimensions of images. In addition, we describe and validate a
      computational improvement to box-counting fractal analysis. This improvement is
      based on integral images, which allows the speedup of any box-counting or similar
      fractal analysis algorithm, including estimation of scale-dependent dimensions.
      Finally, we applied our technique to images of invasive breast cancer tissue from
      157 patients to show a relationship between the fractal analysis of these images
      over certain scale ranges and pathologic tumour grade (a standard prognosticator
      for breast cancer). Our approach is general and can be applied to any medical
      imaging application in which the complexity of pathological image structures may
      have clinical value. 

PMID- 24023587
TI  - Intradiscal Pressure Changes during Manual Cervical Distraction: A Cadaveric
      Study.
AB  - The objective of this study was to measure intradiscal pressure (IDP) changes in
      the lower cervical spine during a manual cervical distraction (MCD) procedure.
      Incisions were made anteriorly, and pressure transducers were inserted into each
      nucleus at lower cervical discs. Four skilled doctors of chiropractic (DCs)
      performed MCD procedure on nine specimens in prone position with contacts at C5
      or at C6 vertebrae with the headpiece in different positions. IDP changes,
      traction forces, and manually applied posterior-to-anterior forces were analyzed
      using descriptive statistics. IDP decreases were observed during MCD procedure at
      all lower cervical levels C4-C5, C5-C6, and C6-C7. The mean IDP decreases were as
      high as 168.7 KPa. Mean traction forces were as high as 119.2 N. Posterior-to
      anterior forces applied during manual traction were as high as 82.6 N.
      Intraclinician reliability for IDP decrease was high for all four DCs. While two
      DCs had high intraclinician reliability for applied traction force, the other two
      DCs demonstrated only moderate reliability. IDP decreases were greatest during
      moving flexion and traction. They were progressevely less pronouced with neutral
      traction, fixed flexion and traction, and generalized traction. 

PMID- 24023589
TI  - Further insight into the depth-dependent microstructural response of cartilage to
      compression using a channel indentation technique.
AB  - Stress relaxation and structural analysis were used to investigate the zonally
      differentiated microstructural response to compression of the integrated
      cartilage-on-bone tissue system. Fifteen cartilage-on-bone samples were divided
      into three equal groups and their stress relaxation responses obtained at three
      different levels of axial compressive strain defined as low (~20%), medium (~40%)
      and high (~60%). All tests were performed using a channel indenter which included
      a central relief space designed to capture the response of the matrix adjacent to
      the directly loaded regions. On completion of each stress relaxation test and
      while maintaining the imposed axial strain, the samples were formalin fixed,
      decalcified, and then sectioned for microstructural analysis. Chondron aspect
      ratios were used to determine the extent of relative strain at different zonal
      depths. The stress relaxation response of cartilage to all three defined levels
      of axial strain displayed an initial highly viscous response followed by a
      significant elastic response. Chondron aspect ratio measurements showed that at
      the lowest level of compression, axial deformation was confined to the
      superficial cartilage layer, while in the medium and high axial strain samples
      the deformation extended into the midzone. The cells in the deep zone remained
      undeformed for all compression levels. 

PMID- 24023590
TI  - Long term Anticoagulation at Crossroads.

PMID- 24023591
TI  - Hypertension in romanian children and adolescents: a cross-sectional survey.
AB  - AIM: Knowledge of the existence of a prolonged action of cardiovascular risk
      factors since childhood is extremely important in a country with one of the
      highest cardiovascular mortality in Europe. The purpose of this survey was to
      study the prevalence of arterial hypertension (AH) and cardiovascular risk
      factors in Romanian paediatric population. METHODS: Children and adolescents
      (2407 males, 2459 females), aged 3 to 17 years from Bucharest and Ilfov County
      were admitted in a cross-sectional survey. Body weight, height, and blood
      pressure (BP) were measured and the percentiles for height, BP and body mass
      index were established. An interviewer-administered questionnaire about some
      presumed risk factors was used. RESULTS: The prevalence of AH in our population
      was 7.4%. In Bucharest AH prevalence was 8% and in rural areas 6.8% (P=0.69). AH
      prevalence was higher both in overweight (12.4%) and obese (24.4%) groups
      comparing with normal weight (5.8%), (P<0.0001). In the underweight group, AH
      prevalence was 3.8%. We found statistically significant the association between
      male gender and SH (P=0.032). While SH increases with age (P=0.015), diastolic DH
      decreases with age (P=0.0003). We found no correlation between AH in children and
      adolescents and consumption of caffeinated beverages, family history of
      cardiovascular disease, smoking, low birth weight, sleep disorders and abnormal
      sleep duration, absence of extra-school sport activity. CONCLUSION: The high AH
      prevalence together with overweight or obesity represent cardiovascular risk
      factors, identified within our population.

PMID- 24023592
TI  - Growth hormone response to clonidine administration for evaluation of autonomic
      dysfunction in multiple sclerosis patients.
AB  - OBJECTIVES: Our objective was to assess the dynamic serum growth hormone (GH)
      response to clonidine administration in multiple sclerosis patients, looking for
      a possible biomarker of degenerative process and to correlative with disability.
      METHODS: 21 patients with relapsing remitting multiple sclerosis, who were
      evaluated clinically by expanded disability status scale (EDSS) score and
      multiple sclerosis functional composite (MSFC) score and for whom we measured the
      GH before and one hour after oral clonidine administration.Different cut-off
      values of EDSS score were chosen for observation of GH serum dynamics after
      clonidine administration. All patients had normal IGF1 values. RESULTS: There was
      a significant positive correlation between EDSS and time to walk 25 feet (r =
      0.5, p = 0.002) and EDSS and nine holes peg tests for dominant and non dominant
      hands (r = 0.37, p = 0.024 and r = 0.53, p = 0.001, respectively).There was a
      moderate negative correlation, significant statistically, between EDSS and paced
      auditory serial additional test (PASAT) (r= -0.36, p= 0.046).4 out of 7 patients
      with EDSS score over 3.0 failed to increase serum GH levels after clonidine
      administration, as compared to 4 out of 14 patients with EDSS < 3 (r = 1.6;
      p=0.02), revealed by means of the Pearson chi square test. CONCLUSION: Despite
      the small number of subjects enrolled in this pilot study, there is a tendency of
      blunted GH response in patients with more severe physical disability (stated by
      an increased value of EDSS), suggesting that GH response to clonidine could
      assess central autonomic dysfunction in MS patients.

PMID- 24023593
TI  - Perception on adverse drug reaction reporting by physicians working in southern
      romania.
AB  - AIM: The purpose of our study was to investigate and to assess the perceptions
      of Romanian doctors towards adverse drug reactions (ADRs) reporting. METHOD: A
      questionnaire with 20 items accompanied by a letter presenting the study was
      circulated using Internet and face to face interviews to 532 doctors in Bucharest
      and two neighboring regions from Romania (Muntenia and Oltenia). RESULTS: 204
      (56.2%) of the total number of responders expressed their opinion that the daily
      number of ADRs observed to be under 5 309 (58%) of responders were never informed
      about ADRs reporting, 439 (82.52%) did not know that the Romanian College of
      Physicians is scoring this activity under the "Continuous medical education
      program". Factors that might encourage voluntary reporting of adverse reactions
      were identified to be: the easiness of reporting, their periodic information and
      the training about all adverse reactions reported by doctors and the measures
      taken. Factors discouraging voluntary reporting of an adverse drug reaction were:
      the lack of information on where, when and how to report ADRs, the uncertain
      causality. CONCLUSION: Currently, the pharmacovigilance activities including
      reporting of ADRs in Romania are more of an accidental nature, doctors are less
      or not at all informed about this activity. Doctors have a favorable attitude
      towards reporting ADRs - as the majority believes that the reporting should be
      either voluntary or mandatory as opposed to a small number that would expect to
      be paid for this activity.

PMID- 24023594
TI  - Post renal transplant type 2 diabetes mellitus in a case of familial juvenile
      nephrophthisis.
AB  - Familial juvenile nephronophtisis, an autosomal recessive tubulointerstitial
      chronic nephritis, is characterized by progressive renal disease and end stage
      renal failure, which require kidney transplantation. Post-transplant diabetes
      mellitus (PTDM) incidence after kidney transplantation varies from 4-25%.
      Obesity, positive oral glucose tolerance test, metabolic syndromes, and post
      transplantation multi-drug, high dose, long-term immunosuppressive therapy are
      the risk factors incriminated.We present the case of a 15-year-old overweight boy
      who was diagnosed with familial juvenile nephronophtisis five years before,
      afterwards progressive renal disease and end stage renal failure. This young
      patient developed PTDM three years after renal transplantation. His underweight
      brother, with the same medical history, did not develop PTDM.Transplantation was
      mandatory for a child with familial juvenile nephronophtisis.The case illustrates
      the risk factors for PTDM. 

PMID- 24023595
TI  - Unilateral pulmonary hilar tumor mass: is it always lung cancer?
AB  - Sarcoidosis is a multisystem inflammatory disease of unknown etiology,
      characterized by noncaseating epithelioid cell granulomas. In sarcoidosis, the
      most common radiological findings are mediastinal and bilateral hilar lymph node
      enlargement. We present a case of sarcoidosis with a rare radiological aspect of
      pulmonary hilar tumor mass.A 54-year-old female patient, active smoker (40
      packs/year), with a history of cutaneous lupus, was admitted in our institute for
      progressive dyspnea and dry cough. At admission physical examination and
      laboratory tests were normal. Pulmonary function tests diagnosed an obstructive
      syndrome. Chest X-ray showed a tumor mass of the right pulmonary hilum.
      Transbronchial biopsy was nondiagnostic. HRCT-scan showed a tumor mass in the
      right hilum, which raised the suspicion of a lung cancer. PET-CT scan revealed a
      high metabolic activity of the tumor mass and of a paratracheal right
      lymphadenopathy. Lymph node biopsy by mediastinoscopy showed noncaseating
      epithelioid-cell granulomas, sustaining the diagnosis of sarcoidosis. The outcome
      was favorable, with spontaneous remission without treatment, but with a relapse
      that responded after systemic corticotherapy.In conclusion, even if a tumor mass
      in the pulmonary hilum is highly suggestive of lung cancer, a positive diagnosis
      should be made only after histological examination, because other benign
      conditions, like sarcoidosis, could have such an aspect. 

PMID- 24023596
TI  - Titanium preformed implants in orbital floor reconstruction - case presentation,
      review of literature.
AB  - The management of orbital fractures is one of the most interesting and difficult
      areas in facial trauma. The consequences of an orbital fracture are sometimes
      dramatic. They include varying types of defects from a loss of vision to
      diplopia, loss of an eye, epiphora, a disturbing loss of facial sensation, or
      even an unacceptable appearance of the eye and the hard and soft tissues around
      it. The controversies surrounding orbital fractures, and orbital floor fractures
      in particular include the following: the timing of primary surgery (early or
      late), bone grafting versus alloplastic materials, the management and prevention
      of diplopia, the prevention of enophtalmos, the management of infraorbital nerve
      numbness or dysesthesia. 

PMID- 24023597
TI  - Uncommon Presentation of Meckel's Diverticulum in Young Age.
AB  - Meckel's diverticulum is a rare detected anomaly.We present the case of a 13
      months old male toddler dead shortly after he was admitted to the hospital. On
      internal autopsy examination abdominal dissection cream-brown fluid in abdomen
      was observed. In the ileum, 45 cm proximal to the ileocecal valve, 1 cm in
      diameter perforation area was detected, ongoing dissection revealed diverticular,
      pouch like structure, Meckel's diverticulum. We presented perforated Meckel's
      diverticulum detected at autopsy. 

PMID- 24023598
TI  - Tropomyosin-receptor-kinases signaling in the nervous system.
AB  - ABSTRACT: The development and function of the nervous system is dependent on many
      growth factors and their signaling. Tropomyosin-receptor-kinase receptor family
      controls synaptic strength and plasticity in the mammalian nervous system.
      Dysregulation of Tropomyosin-receptor-kinase receptors signaling can lead to
      neural developmental disorders and has been reported in certain diseases of the
      nervous system. Apart from their role in the nervous system, these tyrosine
      kinase receptors are also involved in cancer biology. Tropomyosin-receptor
      kinases and their ligands, neurotrophins, are also involved in neural precursor
      stem cells differentiation. This review focuses on Tropomyosin-receptor-kinases,
      the most abundant receptors in mammalian nervous system.

PMID- 24023599
TI  - Paraoxonases as protective agents against N-acyl homoserine lactone - producing
      pathogenic microorganisms.
AB  - ABSTRACT: Paraoxonases are a group of enzymes with a high "substrate
      promiscuity", being able to act on many structurally different compounds. To
      date, there is no consensus regarding the physiological substrate(s) of these
      enzymes. Recent data suggest that the N-acyl homoserine lactones (AHLs) produced
      by different Gram-negative bacteria, including the opportunistic Pseudomonas
      aeruginosa, could be such substrates. Due to the ability of paraoxonases to
      hydrolyze AHLs, they represent an alternative mechanism of protection against
      pathogen microorganisms, interfering with the quorum sensing systems that allow
      these bacteria to respond in a coordinate manner to different changes in the
      extracellular environment. This mini-review presents some novel aspects regarding
      the relationship between paraoxonases and the aforementioned compounds,
      highlighting the potential role of these enzymes as a component of the humoral
      innate defence system.

PMID- 24023600
TI  - History of BCG Vaccine.
AB  - Tuberculosis (TB) is still responsible for 2 million deaths every year despite
      being a treatable airborne infectious disease. "Consumption" and "Phthisis" were
      terms historically used to describe TB, which was responsible for one in four
      deaths in the 19th century. Due to its infectious nature, chronic progression and
      long treatment, TB is a great burden for society. Moreover the emergence of multi
      drug resistant TB and the current TB-HIV epidemic has raised even greater
      concern. Treating and preventing TB has become a permanent challange since the
      ancient times. Bacille Calmette-Guerin (BCG) is the only vaccine available today
      and has been used for more than 90 years with astonishing safety records.
      However, its efficacy remains controversial. No universal BCG vaccination policy
      exists, with some countries merely recommending its use and others that have
      implemented immunization programs. In this article we review several important
      milestones of BCG vaccine development from the discovery till today. 

PMID- 24023601
TI  - Chemotherapy-induced Cardiotoxicity.
AB  - Breast cancer represents the most frequent form of neoplasia in women worldwide,
      being responsible of 1.6% of annual deaths. Therefore, it is a major public
      health issue and research in this field should be a priority. Chemoterapics drugs
      are extremly potent tools, which alone or in association to radiotherapy,
      increase survival and lower the reccurrence rate of cancer, but their use can be
      limited by cardiotoxicity. Cardiotoxicity can appear early or late after therapy,
      and may vary from subclinical myocardial dysfunction to irreversible heart
      failure. Currently, cardiac dysfunction induced by chemotherapy is diagnosed
      through classical echocardiographic parameters. However, these cannot detect
      subtle, early changes of cardiac structure and function. Consequently,
      description of new methods, which could detect cardiac dysfunction in an early
      stage, becomes essential for detecting the group of patients at risk for
      irreversible heart failure and for monitoring the treatment. 

PMID- 24023602
TI  - Functional dyspepsia today.
AB  - Functional dyspepsia (FD) is a disorder presenting with symptoms such as
      postprandial fullness, early satiety or epigastric pain. Although there is a 10
      to 30% reported prevalence worldwide, there is currently no clear explanation of
      the pathophysiology behind this condition. Motility disorders, visceral
      hypersensitivity, acid disorders, Helicobacter pylori infection or psychosocial
      factors have all been reported to play a part in the pathophysiology of FD. The
      diagnosis of FD is one of exclusion, based on the Rome III criteria. The main
      therapeutic modalities include lifestyle changes, eradicating Helicobacter pylori
      infection and treatment with either proton pump inhibitors, prokinetics or
      antidepressants. 

PMID- 24023603
TI  - Role of leptin in autoimmune diseases.
AB  - Leptin represents a link between metabolism, nutritional status, and immune
      responses. Leptin is important for optimal functioning of the immune system.
      Leptin is a cytokine-like hormone with proinflammatory properties linked to
      autoimmune diseases. Moreover, there has been increasing evidence that leptin is
      involved in the pathogenesis of various autoimmune diseases. Leptin has been
      shown to enhance immune reactions in autoimmune diseases that are commonly
      associated with inflammatory responses. Both high and low levels of leptin might
      contribute to autoimmune diseases. Leptin has been explored as a potential target
      for therapeutic development in treating autoimmune diseases. In this review, we
      review here the most recent advances on the role of leptin in autoimmunity and in
      immune-rheumatological diseases. 

PMID- 24023604
TI  - Multiple cancers of the head and neck.
AB  - Multiple head and neck cancers are not rare entities and according to studies in
      the literature, their incidence is increasing. The emergence of multiple cancers
      is explained by the phenomenon of "field cancerization". Patients with cancer of
      the upper digestive and respiratory tract develop most often a second malignancy,
      usually in the upper aero-digestive tract and among them, those with larynx
      cancer ranks first among patients with multiple cancers. In the literature and in
      practice, we met rare combination of multiple cancers, associations that appear
      to be "random", cannot be explained by any of the hypotheses developed: exposure
      to carcinogens, genetic susceptibility, and immunodeficiency or cancer treatments
      after index tumor. Follow-up of patients who have had a head and neck cancer and
      periodic control are important for early detection of multiple cancers. 

PMID- 24023605
TI  - The challenge of corporeity: fictionalising the emotional body.
AB  - Geoffrey Chaucer's Troilus and Criseyde (ca. 1380) writes emotions as corporeal
      events unfolding as specific sensorimotor, cognitive actions, which, in
      particular cases, may develop pathological offshoots. This paper explores the
      unstable, organic quality of the emotional phenomenon, and its fluid formal
      potential. Indeed, while emotion resists definitive categorical and conceptual
      containment, it must be named, made sense of, thus signalling the power of
      corporeity to shape language and thought. Crucially, this allows us to measure
      the importance of cognitive and epistemological modes we activate with the
      purpose of grasping emotion as irreducible aspect of the human. In this sense,
      poetic expression emerges as a necessity: through continuous actualisation of its
      formal plasticity, literature enables the provisory encoding and circulation of
      emotional phenomena, by exploring the interface between a perceiving body and its
      phenomenal environment, while allowing for the emergence of new modes of
      thinking. I proceed to a transepistemic examination of the text in question, by
      means of historically-informed conceptual tools, beyond the inappropriate
      categorical dissonances between body and mind, affect and intellect, philosophy,
      literature, and science. 

PMID- 24023607
TI  - Whey protein hydrolysate increases translocation of GLUT-4 to the plasma membrane
      independent of insulin in wistar rats.
AB  - Whey protein (WP) and whey protein hydrolysate (WPH) have the recognized capacity
      to increase glycogen stores. The objective of this study was to verify if
      consuming WP and WPH could also increase the concentration of the glucose
      transporters GLUT-1 and GLUT-4 in the plasma membrane (PM) of the muscle cells of
      sedentary and exercised animals. Forty-eight Wistar rats were divided into 6
      groups (n = 8 per group), were treated and fed with experimental diets for 9 days
      as follows: a) control casein (CAS); b) WP; c) WPH; d) CAS exercised; e) WP
      exercised; and f) WPH exercised. After the experimental period, the animals were
      sacrificed, muscle GLUT-1 and GLUT-4, p85, Akt and phosphorylated Akt were
      analyzed by western blotting, and the glycogen, blood amino acids, insulin levels
      and biochemical health indicators were analyzed using standard methods.
      Consumption of WPH significantly increased the concentrations of GLUT-4 in the PM
      and glycogen, whereas the GLUT-1 and insulin levels and the health indicators
      showed no alterations. The physical exercise associated with consumption of WPH
      had favorable effects on glucose transport into muscle. These results should
      encourage new studies dealing with the potential of both WP and WPH for the
      treatment or prevention of type II diabetes, a disease in which there is reduced
      translocation of GLUT-4 to the plasma membrane. 

PMID- 24023608
TI  - Increase in sialylation and branching in the mouse serum N-glycome correlates
      with inflammation and ovarian tumour progression.
AB  - Ovarian cancer is the most lethal gynaecological cancer and is often diagnosed in
      late stage, often as the result of the unavailability of sufficiently sensitive
      biomarkers for early detection, tumour progression and tumour-associated
      inflammation. Glycosylation is the most common posttranslational modification of
      proteins; it is altered in cancer and therefore is a potential source of
      biomarkers. We investigated the quantitative and qualitative effects of anti
      inflammatory (acetylsalicylic acid) and pro-inflammatory (thioglycolate and
      chlorite-oxidized oxyamylose) drugs on glycosylation in mouse cancer serum. A
      significant increase in sialylation and branching of glycans in mice treated with
      an inflammation-inducing compound was observed. Moreover, the increases in
      sialylation correlated with increased tumour sizes. Increases in sialylation and
      branching were consistent with increased expression of sialyltransferases and the
      branching enzyme MGAT5. Because the sialyltransferases are highly conserved among
      species, the described changes in the ovarian cancer mouse model are relevant to
      humans and serum N-glycome analysis for monitoring disease treatment and
      progression might be a useful biomarker. 

PMID- 24023609
TI  - Modulatory interactions of resting-state brain functional connectivity.
AB  - The functional brain connectivity studies are generally based on the
      synchronization of the resting-state functional magnetic resonance imaging (fMRI)
      signals. Functional connectivity measures usually assume a stable relationship
      over time; however, accumulating studies have reported time-varying properties of
      strength and spatial distribution of functional connectivity. The present study
      explored the modulation of functional connectivity between two regions by a third
      region using the physiophysiological interaction (PPI) technique. We first
      identified eight brain networks and two regions of interest (ROIs) representing
      each of the networks using a spatial independent component analysis. A voxel-wise
      analysis was conducted to identify regions that showed modulatory interactions
      (PPI) with the two ROIs of each network. Mostly, positive modulatory interactions
      were observed within regions involved in the same system. For example, the two
      regions of the dorsal attention network revealed modulatory interactions with the
      regions related to attention, while the two regions of the extrastriate network
      revealed modulatory interactions with the regions in the visual cortex. In
      contrast, the two regions of the default mode network (DMN) revealed negative
      modulatory interactions with the regions in the executive network, and vice
      versa, suggesting that the activities of one network may be associated with
      smaller within network connectivity of the competing network. These results
      validate the use of PPI analysis to study modulation of resting-state functional
      connectivity by a third region. The modulatory effects may provide a better
      understanding of complex brain functions. 

PMID- 24023610
TI  - Adaptation of maize to temperate climates: mid-density genome-wide association
      genetics and diversity patterns reveal key genomic regions, with a major
      contribution of the Vgt2 (ZCN8) locus.
AB  - The migration of maize from tropical to temperate climates was accompanied by a
      dramatic evolution in flowering time. To gain insight into the genetic
      architecture of this adaptive trait, we conducted a 50K SNP-based genome-wide
      association and diversity investigation on a panel of tropical and temperate
      American and European representatives. Eighteen genomic regions were associated
      with flowering time. The number of early alleles cumulated along these regions
      was highly correlated with flowering time. Polymorphism in the vicinity of the
      ZCN8 gene, which is the closest maize homologue to Arabidopsis major flowering
      time (FT) gene, had the strongest effect. This polymorphism is in the vicinity of
      the causal factor of Vgt2 QTL. Diversity was lower, whereas differentiation and
      LD were higher for associated loci compared to the rest of the genome, which is
      consistent with selection acting on flowering time during maize migration.
      Selection tests also revealed supplementary loci that were highly differentiated
      among groups and not associated with flowering time in our panel, whereas they
      were in other linkage-based studies. This suggests that allele fixation led to a
      lack of statistical power when structure and relatedness were taken into account
      in a linear mixed model. Complementary designs and analysis methods are necessary
      to unravel the architecture of complex traits. Based on linkage disequilibrium
      (LD) estimates corrected for population structure, we concluded that the number
      of SNPs genotyped should be at least doubled to capture all QTLs contributing to
      the genetic architecture of polygenic traits in this panel. These results show
      that maize flowering time is controlled by numerous QTLs of small additive effect
      and that strong polygenic selection occurred under cool climatic conditions. They
      should contribute to more efficient genomic predictions of flowering time and
      facilitate the dissemination of diverse maize genetic resources under a wide
      range of environments. 

PMID- 24023612
TI  - Replication and meta-analysis of GWAS identified susceptibility loci in Kawasaki
      disease confirm the importance of B lymphoid tyrosine kinase (BLK) in disease
      susceptibility.
AB  - The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two
      genome-wide association studies (GWAS) conducted in a Taiwanese population of Han
      Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these
      findings with replication studies of the BLK and CD40 loci in populations of
      Korean and European descent. The BLK region was significantly associated with KD
      susceptibility in both populations. Within the BLK gene the rs2736340-located
      linkage disequilibrium (LD ) comprising the promoter and first intron was
      strongly associated with KD, with the combined results of Asian studies including
      Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021
      controls) providing very compelling evidence of association (rs2736340, OR =
      1.498, 1.354-1.657; P = 4.74*10(-31)). We determined the percentage of B cells
      present in the peripheral blood mononuclear cell (PBMC) population and the
      expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients
      during the acute and convalescent stages. The percentage of B cells in the PBMC
      population and the expression of BLK in leukocytes were induced in patients in
      the acute stage of KD. In B cell lines derived from KD patients, and in purified
      B cells from KD patients obtained during the acute stage, those with the risk
      allele of rs2736340 expressed significantly lower levels of BLK. These results
      suggest that peripheral B cells play a pathogenic role during the acute stage of
      KD. Decreased BLK expression in peripheral blood B cells may alter B cell
      function and predispose individuals to KD. These associative data suggest a role
      for B cells during acute KD. Understanding the functional implications may
      facilitate the development of B cell-mediated therapy for KD. 

PMID- 24023613
TI  - A qualitative analysis of factors influencing HPV vaccine uptake in Soweto, South
      Africa among adolescents and their caregivers.
AB  - BACKGROUND: In South Africa, the prevalence of oncogenic Human Papillomavirus
      (HPV) may be as high as 64%, and cervical cancer is the leading cause of cancer
      related death among women. The development of efficacious prophylactic vaccines
      has provided an opportunity for primary prevention. Given the importance of
      psycho-social forces in vaccine uptake, we sought to elucidate factors
      influencing HPV vaccination among a sample of low-income South African
      adolescents receiving the vaccine for the first time in Soweto. METHODS: The HPV
      vaccine was introduced to adolescents in low-income townships throughout South
      Africa as part of a nationwide trial to understand adolescent involvement in
      future vaccine research targeting human immunodeficiency virus (HIV). We
      performed in-depth semi-structured interviews with purposively-sampled
      adolescents and their care providers to understand what forces shaped HPV vaccine
      uptake. Interviews were recorded, transcribed, translated, and examined using
      thematic analysis. RESULTS: Of 224 adolescents recruited, 201 initiated the
      vaccine; 192 (95.5%) received a second immunization; and 164 (81.6%) completed
      three doses. In our qualitative study of 39 adolescent-caregiver dyads, we found
      that factors driving vaccine uptake reflected a socio-cultural backdrop of high
      HIV endemnicity, sexual violence, poverty, and an abundance of female-headed
      households. Adolescents exercised a high level of autonomy and often initiated
      decision-making. Healthcare providers and peers provided support and guidance
      that was absent at home. The impact of the HIV epidemic on decision-making was
      substantial, leading participants to mistakenly conflate HPV and HIV.
      CONCLUSIONS: In a setting of perceived rampant sexual violence and epidemic
      levels of HIV, adolescents and caregivers sought to decrease harm by seeking a
      vaccine targeting a sexually transmitted infection (STI). Despite careful
      consenting, there was confusion regarding the vaccine's target. Future
      interventions promoting STI vaccines will need to provide substantial information
      for participants, particularly adolescents who may exercise a significant level
      of autonomy in decision-making.

PMID- 24023614
TI  - Malnutrition has no effect on the timing of human tooth formation.
AB  - The effect of nutrition on the timing of human tooth formation is poorly
      understood. Delays and advancements in dental maturation have all been reported
      as well as no effect. We investigated the effect of severe malnutrition on the
      timing of human tooth formation in a large representative sample of North
      Sudanese children. The sample (1102 males, 1013 females) consisted of stratified
      randomly selected healthy individuals in Khartoum, Sudan, aged 2-22 years using a
      cross-sectional design following the STROBE statement. Nutritional status was
      defined using WHO criteria of height and weight. Body mass index Z-scores and
      height for age Z-scores of <=-2 (cut-off) were used to identify the malnourished
      group (N = 474) while the normal was defined by Z-scores of >=0 (N = 799).
      Clinical and radiographic examination of individuals, with known ages of birth
      was performed including height and weight measurements. Mandibular left permanent
      teeth were assessed using eight crown and seven root established tooth formation
      stages. Mean age at entry and mean age within tooth stages were calculated for
      each available tooth stage in each group and compared using a t-test. Results
      show the mean age at entry and mean age within tooth stages were not
      significantly different between groups affected by severe malnutrition and normal
      children (p>0.05). This remarkable finding was evident across the span of dental
      development. We demonstrate that there is little measurable effect of sustained
      malnutrition on the average timing of tooth formation. This noteworthy finding
      supports the notion that teeth have substantial biological stability and are
      insulated from extreme nutritional conditions compared to other maturing body
      systems. 

PMID- 24023611
TI  - Genomic investigation into strain heterogeneity and pathogenic potential of the
      emerging gastrointestinal pathogen Campylobacter ureolyticus.
AB  - The recent detection and isolation of C. ureolyticus from patients with
      diarrhoeal illness and inflammatory bowel diseases warrants further investigation
      into its role as an emerging pathogen of the human gastrointestinal tract.
      Regarding the pathogenic mechanisms employed by this species we provide the first
      whole genome analysis of two C. ureolyticus isolates including the type strain.
      Comparative analysis, subtractive hybridisation and gene ontology searches
      against other Campylobacter species identifies the high degree of heterogenicity
      between C. ureolyticus isolates, in addition to the identification of 106
      putative virulence associated factors, 52 of which are predicted to be secreted.
      Such factors encompass each of the known virulence tactics of pathogenic
      Campylobacter spp. including adhesion and colonisation (CadF, PEB1, IcmF and
      FlpA), invasion (ciaB and 16 virB-virD4 genes) and toxin production (S-layer RTX
      and ZOT). Herein, we provide the first virulence catalogue for C. ureolyticus,
      the components of which theoretically provide this emerging species with
      sufficient arsenal to establish pathology. 

PMID- 24023615
TI  - Spatio-temporal environmental correlation and population variability in simple
      metacommunities.
AB  - Natural populations experience environmental conditions that vary across space
      and over time. This variation is often correlated between localities depending on
      the geographical separation between them, and different species can respond to
      local environmental fluctuations similarly or differently, depending on their
      adaptation. How this emerging structure in environmental correlation (between
      patches and between-species) affects spatial community dynamics is an open
      question. This paper aims at a general understanding of the interactions between
      the environmental correlation structure and population dynamics in spatial
      networks of local communities (metacommunities), by studying simple two-patch,
      two-species systems. Three different pairs of interspecific interactions are
      considered: competition, consumer-resource interaction, and host-parasitoid
      interaction. While the results paint a relatively complex picture of the effect
      of environmental correlation, the interaction between environmental forcing,
      dispersal, and local interactions can be understood via two mechanisms. While
      increasing between-patch environmental correlation couples immigration and local
      densities (destabilising effect), the coupling between local populations under
      increased between-species environmental correlation can either amplify or dampen
      population fluctuations, depending on the patterns in density dependence. This
      work provides a unifying framework for modelling stochastic metacommunities, and
      forms a foundation for a better understanding of population responses to
      environmental fluctuations in natural systems. 

PMID- 24023616
TI  - Beyond precipitation: physiographic gradients dictate the relative importance of
      environmental drivers on Savanna vegetation.
AB  - BACKGROUND: Understanding the drivers of large-scale vegetation change is
      critical to managing landscapes and key to predicting how projected climate and
      land use changes will affect regional vegetation patterns. This study aimed to
      improve our understanding of the role, magnitude and spatial distribution of the
      key environmental factors driving vegetation change in southern African savanna,
      and how they vary across physiographic gradients. METHODOLOGY/PRINCIPAL FINDINGS:
      We applied Dynamic Factor Analysis (DFA), a multivariate times series dimension
      reduction technique to ten years of monthly remote sensing data (MODIS-derived
      normalized difference vegetation index, NDVI) and a suite of environmental
      covariates: precipitation, mean and maximum temperature, soil moisture, relative
      humidity, fire and potential evapotranspiration. Monthly NDVI was described by
      cyclic seasonal variation with distinct spatiotemporal patterns in different
      physiographic regions. Results support existing work emphasizing the importance
      of precipitation, soil moisture and fire on NDVI, but also reveal overlooked
      effects of temperature and evapotranspiration, particularly in regions with
      higher mean annual precipitation. Critically, spatial distributions of the
      weights of environmental covariates point to a transition in the importance of
      precipitation and soil moisture (strongest in grass-dominated regions with
      precipitation<750 mm) to fire, potential evapotranspiration, and temperature
      (strongest in tree-dominated regions with precipitation>950 mm).
      CONCLUSIONS/SIGNIFICANCE: We quantified the combined spatiotemporal effects of an
      available suite of environmental drivers on NDVI across a large and diverse
      savanna region. The analysis supports known drivers of savanna vegetation but
      also uncovers important roles of temperature and evapotranspiration. Results
      highlight the utility of applying the DFA approach to remote sensing products for
      regional analyses of landscape change in the context of global environmental
      change. With the dramatic increase in global change research, this methodology
      augurs well for further development and application of spatially explicit time
      series modeling to studies at the intersection of ecology and remote sensing.

PMID- 24023617
TI  - RAG-1 and Ly6D independently reflect progression in the B lymphoid lineage.
AB  - Common lymphoid progenitors (CLPs) are thought to represent major intermediates
      in the transition of hematopoietic stem cells (HSCs) to B lineage lymphocytes.
      However, it has been obvious for some time that CLPs are heterogeneous, and there
      has been controversy concerning their differentiation potential. We have now
      resolved four Flt3(+) CLP subsets that are relatively homogenous and capable of
      forming B cells. Differentiation potential and gene expression patterns suggest
      Flt3(+) CLPs lacking both Ly6D and RAG-1 are the least differentiated. In
      addition to B cells, they generate natural killer (NK) and dendritic cells (DCs).
      At the other extreme is a subset of the recently described Flt3(+) Ly6D(+) CLPs
      that have a history of RAG-1 expression and are B lineage restricted. These
      relatively abundant and potent CLPs were depleted within 48 hours of acute in
      vivo estrogen elevation, suggesting they descend from hormone regulated
      progenitors. This contrasts with the hormone insensitivity of other CLP subsets
      that include NK lineage progenitors. This progenitor heterogeneity and
      differentiation complexity may add flexibility in response to environmental
      changes. Expression of RAG-1 and display of Ly6D are both milestone events, but
      they are neither synchronized nor dependent on each other. 

PMID- 24023618
TI  - Get in my belly: food preferences trigger approach and avoidant postural
      asymmetries.
AB  - Appetitive motivational states are fundamental neural and behavioral mechanisms
      underlying healthy and abnormal eating behavior, though their dynamic influence
      on food-related behavior is unknown. The present study examined whether personal
      food-related preferences would activate approach and avoidance systems,
      modulating spontaneous postural sway toward and away from food items.
      Participants stood on a balance board that collected real-time data regarding
      postural sway along two axes (x, y) while they viewed a series of images
      depicting food items varying in nutritional value and individual preferences.
      Overall, participants showed reliable postural sway toward highly preferred and
      away from highly non-preferred items. This effect became more pronounced over
      time; sway along the mediolateral axis showed no reliable variation by
      preference. Results carry implications for two-factor (homeostatic versus
      hedonic) neurobehavioral theories of hunger and appetitive motivation, and carry
      applied clinical implications for the measurement and management of abnormal
      eating behavior. 

PMID- 24023619
TI  - Total protein analysis as a reliable loading control for quantitative fluorescent
      Western blotting.
AB  - Western blotting has been a key technique for determining the relative expression
      of proteins within complex biological samples since the first publications in
      1979. Recent developments in sensitive fluorescent labels, with truly
      quantifiable linear ranges and greater limits of detection, have allowed
      biologists to probe tissue specific pathways and processes with higher resolution
      than ever before. However, the application of quantitative Western blotting (QWB)
      to a range of healthy tissues and those from degenerative models has highlighted
      a problem with significant consequences for quantitative protein analysis: how
      can researchers conduct comparative expression analyses when many of the commonly
      used reference proteins (e.g. loading controls) are differentially expressed?
      Here we demonstrate that common controls, including actin and tubulin, are
      differentially expressed in tissues from a wide range of animal models of
      neurodegeneration. We highlight the prevalence of such alterations through
      examination of published "-omics" data, and demonstrate similar responses in
      sensitive QWB experiments. For example, QWB analysis of spinal cord from a murine
      model of Spinal Muscular Atrophy using an Odyssey scanner revealed that beta
      actin expression was decreased by 19.3+/-2% compared to healthy littermate
      controls. Thus, normalising QWB data to beta-actin in these circumstances could
      result in 'skewing' of all data by ~20%. We further demonstrate that differential
      expression of commonly used loading controls was not restricted to the nervous
      system, but was also detectable across multiple tissues, including bone, fat and
      internal organs. Moreover, expression of these "control" proteins was not
      consistent between different portions of the same tissue, highlighting the
      importance of careful and consistent tissue sampling for QWB experiments.
      Finally, having illustrated the problem of selecting appropriate single protein
      loading controls, we demonstrate that normalisation using total protein analysis
      on samples run in parallel with stains such as Coomassie blue provides a more
      robust approach. 

PMID- 24023620
TI  - New preclinical antimalarial drugs potently inhibit hepatitis C virus genotype 1b
      RNA replication.
AB  - BACKGROUND: Persistent hepatitis C virus (HCV) infection causes chronic liver
      diseases and is a global health problem. Although new triple therapy (pegylated
      interferon, ribavirin, and telaprevir/boceprevir) has recently been started and
      is expected to achieve a sustained virologic response of more than 70% in HCV
      genotype 1 patients, there are several problems to be resolved, including skin
      rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still
      needed. METHODOLOGY/PRINCIPAL FINDINGS: Recently developed HCV drug assay systems
      using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8)
      were used to evaluate the anti-HCV activity of drug candidates. During the course
      of the evaluation of anti-HCV candidates, we unexpectedly found that two
      preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti
      HCV activities at tens of nanomolar concentrations irrespective of the cell lines
      and HCV strains of genotype 1b. We confirmed that replication of authentic HCV
      RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity
      did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA
      replicating cells were cured by treatment with only N-89. A comparative time
      course assay using N-89 and interferon-alpha demonstrated that N-89-treated ORL8
      cells had more rapid anti-HCV kinetics than did interferon-alpha-treated cells.
      This anti-HCV activity was largely canceled by vitamin E. In combination with
      interferon-alpha and/or ribavirin, N-89 or N-251 exhibited a synergistic
      inhibitory effect. CONCLUSIONS/SIGNIFICANCE: We found that the preclinical
      antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV
      activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may
      be useful as a new type of anti-HCV reagents when used singly or in combination
      with interferon and/or ribavirin.

PMID- 24023621
TI  - The respiratory arsenite oxidase: structure and the role of residues surrounding
      the rieske cluster.
AB  - The arsenite oxidase (Aio) from the facultative autotrophic Alphaproteobacterium
      Rhizobium sp. NT-26 is a bioenergetic enzyme involved in the oxidation of
      arsenite to arsenate. The enzyme from the distantly related heterotroph,
      Alcaligenes faecalis, which is thought to oxidise arsenite for detoxification,
      consists of a large alpha subunit (AioA) with bis-molybdopterin guanine
      dinucleotide at its active site and a 3Fe-4S cluster, and a small beta subunit
      (AioB) which contains a Rieske 2Fe-2S cluster. The successful heterologous
      expression of the NT-26 Aio in Escherichia coli has resulted in the solution of
      its crystal structure. The NT-26 Aio, a heterotetramer, shares high overall
      similarity to the heterodimeric arsenite oxidase from A. faecalis but there are
      striking differences in the structure surrounding the Rieske 2Fe-2S cluster which
      we demonstrate explains the difference in the observed redox potentials (+225 mV
      vs. +130/160 mV, respectively). A combination of site-directed mutagenesis and
      electron paramagnetic resonance was used to explore the differences observed in
      the structure and redox properties of the Rieske cluster. In the NT-26 AioB the
      substitution of a serine (S126 in NT-26) for a threonine as in the A. faecalis
      AioB explains a -20 mV decrease in redox potential. The disulphide bridge in the
      A. faecalis AioB which is conserved in other betaproteobacterial AioB subunits
      and the Rieske subunit of the cytochrome bc 1 complex is absent in the NT-26 AioB
      subunit. The introduction of a disulphide bridge had no effect on Aio activity or
      protein stability but resulted in a decrease in the redox potential of the
      cluster. These results are in conflict with previous data on the
      betaproteobacterial AioB subunit and the Rieske of the bc 1 complex where removal
      of the disulphide bridge had no effect on the redox potential of the former but a
      decrease in cluster stability was observed in the latter. 

PMID- 24023622
TI  - Analysis of gender differences in genetic risk: association of TNFAIP3
      polymorphism with male childhood-onset systemic lupus erythematosus in the
      Japanese population.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic multisystem
      autoimmune disorder influenced by genetic background and environmental factors.
      Our aim here was to replicate findings of associations between 7 of the
      implicated single nucleotide polymorphisms (SNPs) in IRF5, BLK, STAT4, TNFAIP3,
      SPP1, TNIP1 and ETS1 genes with susceptibility to childhood-onset SLE in the
      Japanese population. In particular, we focused on gender differences in allelic
      frequencies. METHODOLOGY/PRINCIPAL FINDINGS: The 7 SNPs were genotyped using
      TaqMan assays in 75 patients with childhood-onset SLE and in 190 healthy
      controls. The relationship between the cumulative number of risk alleles and SLE
      manifestations was explored in childhood-onset SLE. Logistic regression was used
      to test the effect of each polymorphism on susceptibility to SLE, and Wilcoxon
      rank sum testing was used for comparison of total risk alleles. Data on rs7574865
      in the STAT4 gene and rs9138 in SPP1 were replicated for associations with SLE
      when comparing cases and controls (corrected P values ranging from 0.0043 to
      0.027). The rs2230926 allele of TNFAIP3 was associated with susceptibility to SLE
      in males, but after Bonferroni correction there were no significant associations
      with any of the other four SNPs in IRF5, BLK, TNIP1 and ETS1 genes. The
      cumulative number of risk alleles was significantly increased in childhood-onset
      SLE relative to healthy controls (P = 0.0000041). Male SLE patients had a
      slightly but significantly higher frequency of the TNFAIP3 (rs2230926G) risk
      allele than female patients (odds ratio [OR] = 4.05, 95% confidence interval
      [95%CI] = 1.46-11.2 P<0.05). CONCLUSIONS: Associations of polymorphisms in STAT4
      and SPP1 with childhood-onset SLE were confirmed in a Japanese population.
      Although these are preliminary results for a limited number of cases, TNFAIP3
      rs2230926G may be an important predictor of disease onset in males. We also
      replicated findings that the cumulative number of risk alleles was significantly
      increased in childhood-onset SLE.

PMID- 24023623
TI  - Modeling the patient journey from injury to community reintegration for persons
      with acute traumatic spinal cord injury in a Canadian centre.
AB  - BACKGROUND: A patient's journey through the health care system is influenced by
      clinical and system processes across the continuum of care. METHODS: To inform
      optimized access to care and patient flow for individuals with traumatic spinal
      cord injury (tSCI), we developed a simulation model that can examine the full
      impact of therapeutic or systems interventions across the care continuum for
      patients with traumatic spinal cord injuries. The objective of this paper is to
      describe the detailed development of this simulation model for a major trauma and
      a rehabilitation centre in British Columbia (BC), Canada, as part of the Access
      to Care and Timing (ACT) project and is referred to as the BC ACT Model V1.0.
      FINDINGS: To demonstrate the utility of the simulation model in clinical and
      administrative decision-making we present three typical scenarios that illustrate
      how an investigator can track the indirect impact(s) of medical and
      administrative interventions, both upstream and downstream along the continuum of
      care. For example, the model was used to estimate the theoretical impact of a
      practice that reduced the incidence of pressure ulcers by 70%. This led to a
      decrease in acute and rehabilitation length of stay of 4 and 2 days, respectively
      and a decrease in bed utilization of 9% and 3% in acute and rehabilitation.
      CONCLUSION: The scenario analysis using the BC ACT Model V1.0 demonstrates the
      flexibility and value of the simulation model as a decision-making tool by
      providing estimates of the effects of different interventions and allowing them
      to be objectively compared. Future work will involve developing a generalizable
      national Canadian ACT Model to examine differences in care delivery and identify
      the ideal attributes of SCI care delivery.

PMID- 24023624
TI  - Solar ultraviolet irradiation induces decorin degradation in human skin likely
      via neutrophil elastase.
AB  - Exposure of human skin to solar ultraviolet (UV) irradiation induces matrix
      metalloproteinase-1 (MMP-1) activity, which degrades type I collagen fibrils.
      Type I collagen is the most abundant protein in skin and constitutes the majority
      of skin connective tissue (dermis). Degradation of collagen fibrils impairs the
      structure and function of skin that characterize skin aging. Decorin is the
      predominant proteoglycan in human dermis. In model systems, decorin binds to and
      protects type I collagen fibrils from proteolytic degradation by enzymes such as
      MMP-1. Little is known regarding alterations of decorin in response to UV
      irradiation. We found that solar-simulated UV irradiation of human skin in vivo
      stimulated substantial decorin degradation, with kinetics similar to infiltration
      of polymorphonuclear (PMN) cells. Proteases that were released from isolated PMN
      cells degraded decorin in vitro. A highly selective inhibitor of neutrophil
      elastase blocked decorin breakdown by proteases released from PMN cells.
      Furthermore, purified neutrophil elastase cleaved decorin in vitro and generated
      fragments with similar molecular weights as those resulting from protease
      activity released from PMN cells, and as observed in UV-irradiated human skin.
      Cleavage of decorin by neutrophil elastase significantly augmented fragmentation
      of type I collagen fibrils by MMP-1. Taken together, these data indicate that PMN
      cell proteases, especially neutrophil elastase, degrade decorin, and this
      degradation renders collagen fibrils more susceptible to MMP-1 cleavage. These
      data identify decorin degradation and neutrophil elastase as potential
      therapeutic targets for mitigating sun exposure-induced collagen fibril
      degradation in human skin. 

PMID- 24023625
TI  - Surprising prokaryotic and eukaryotic diversity, community structure and
      biogeography of Ethiopian soda lakes.
AB  - Soda lakes are intriguing ecosystems harboring extremely productive microbial
      communities in spite of their extreme environmental conditions. This makes them
      valuable model systems for studying the connection between community structure
      and abiotic parameters such as pH and salinity. For the first time, we apply high
      throughput sequencing to accurately estimate phylogenetic richness and
      composition in five soda lakes, located in the Ethiopian Rift Valley. The lakes
      were selected for their contrasting pH, salinities and stratification and several
      depths or spatial positions were covered in each lake. DNA was extracted and
      analyzed from all lakes at various depths and RNA extracted from two of the
      lakes, analyzed using both amplicon- and shotgun sequencing. We reveal a
      surprisingly high biodiversity in all of the studied lakes, similar to that of
      freshwater lakes. Interestingly, diversity appeared uncorrelated or positively
      correlated to pH and salinity, with the most "extreme" lakes showing the highest
      richness. Together, pH, dissolved oxygen, sodium- and potassium concentration
      explained approximately 30% of the compositional variation between samples. A
      diversity of prokaryotic and eukaryotic taxa could be identified, including
      several putatively involved in carbon-, sulfur- or nitrogen cycling. Key
      processes like methane oxidation, ammonia oxidation and 'nitrifier
      denitrification' were also confirmed by mRNA transcript analyses. 

PMID- 24023626
TI  - Screening accuracy and clinical application of the Brief Infant-Toddler Social
      and Emotional Assessment (BITSEA).
AB  - BACKGROUND: The Brief Infant-Toddler Social and Emotional Assessment (BITSEA) is
      a promising questionnaire for the early detection of psychosocial problems in
      toddlers. The screening accuracy and clinical application were evaluated.
      METHODS: In a community sample of 2-year-olds (N = 2060), screening accuracy of
      the BITSEA Problem scale was examined regarding a clinical CBCL1.5-5 Total
      Problem score. For the total population and subgroups by child's gender and
      ethnicity Receiver Operating Characteristic (ROC) curves were calculated, and
      across a range of BITSEA Problem scores, sensitivity, specificity, likelihood
      ratio's, diagnostic odds ratio and Youden's index. Clinical application of the
      BITSEA was examined by evaluating the relation between the scale scores and the
      clinical decision of the child health professional. RESULTS: The area under the
      ROC curve (95% confidence interval) of the Problem scale was 0.97(0.95-0.98),
      there were no significant differences between subgroups. The association between
      clinical decision and BITSEA Problem score (B = 2.5) and Competence score (B = 
      0.7) was significant (p<0.05). CONCLUSIONS: The results indicate that the BITSEA
      Problem scale has good discriminative power to differentiate children with and
      without psychosocial problems. Referred children had less favourable scores
      compared to children that were not referred. The BITSEA may be helpful in the
      early detection of psychosocial problems.

PMID- 24023627
TI  - Fast growth may impair regeneration capacity in the branching coral Acropora
      muricata.
AB  - Regeneration of artificially induced lesions was monitored in nubbins of the
      branching coral Acropora muricata at two reef-flat sites representing contrasting
      environments at Reunion Island (21 degrees 07'S, 55 degrees 32'E). Growth of
      these injured nubbins was examined in parallel, and compared to controls.
      Biochemical compositions of the holobiont and the zooxanthellae density were
      determined at the onset of the experiment, and the photosynthetic efficiency
      (Fv/Fm ) of zooxanthellae was monitored during the experiment. Acropora muricata
      rapidly regenerated small lesions, but regeneration rates significantly differed
      between sites. At the sheltered site characterized by high temperatures,
      temperature variations, and irradiance levels, regeneration took 192 days on
      average. At the exposed site, characterized by steadier temperatures and lower
      irradiation, nubbins demonstrated fast lesion repair (81 days), slower growth,
      lower zooxanthellae density, chlorophyll a concentration and lipid content than
      at the former site. A trade-off between growth and regeneration rates was evident
      here. High growth rates seem to impair regeneration capacity. We show that
      environmental conditions conducive to high zooxanthellae densities in corals are
      related to fast skeletal growth but also to reduced lesion regeneration rates. We
      hypothesize that a lowered regenerative capacity may be related to limited
      availability of energetic and cellular resources, consequences of coral
      holobionts operating at high levels of photosynthesis and associated growth. 

PMID- 24023628
TI  - Fate of ingested Clostridium difficile spores in mice.
AB  - Clostridium difficile infection (CDI) is a leading cause of antibiotic-associated
      diarrhea, a major nosocomial complication. The infective form of C. difficile is
      the spore, a dormant and resistant structure that forms under stress. Although
      spore germination is the first committed step in CDI onset, the temporal and
      spatial distribution of ingested C. difficile spores is not clearly understood.
      We recently reported that CamSA, a synthetic bile salt analog, inhibits C.
      difficile spore germination in vitro and in vivo. In this study, we took
      advantage of the anti-germination activity of bile salts to determine the fate of
      ingested C. difficile spores. We tested four different bile salts for efficacy in
      preventing CDI. Since CamSA was the only anti-germinant tested able to prevent
      signs of CDI, we characterized CamSa's in vitro stability, distribution, and
      cytotoxicity. We report that CamSA is stable to simulated gastrointestinal (GI)
      environments, but will be degraded by members of the natural microbiota found in
      a healthy gut. Our data suggest that CamSA will not be systemically available,
      but instead will be localized to the GI tract. Since in vitro pharmacological
      parameters were acceptable, CamSA was used to probe the mouse model of CDI. By
      varying the timing of CamSA dosage, we estimated that C. difficile spores
      germinated and established infection less than 10 hours after ingestion. We also
      showed that ingested C. difficile spores rapidly transited through the GI tract
      and accumulated in the colon and cecum of CamSA-treated mice. From there, C.
      difficile spores were slowly shed over a 96-hour period. To our knowledge, this
      is the first report of using molecular probes to obtain disease progression
      information for C. difficile infection. 

PMID- 24023629
TI  - Flexibility of continental navigation and migration in European mallards.
AB  - The ontogeny of continent-wide navigation mechanisms of the individual organism,
      despite being crucial for the understanding of animal movement and migration, is
      still poorly understood. Several previous studies, mainly conducted on
      passerines, indicate that inexperienced, juvenile birds may not generally correct
      for displacement during fall migration. Waterbirds such as the mallard (Anas
      platyrhynchos, Linnaeus 1758) are more flexible in their migration behavior than
      most migratory songbirds, but previous experiments with waterbirds have not yet
      allowed clear conclusions about their navigation abilities. Here we tested
      whether immature mallard ducks correct for latitudinal displacement during fall
      migration within Europe. During two consecutive fall migration periods, we caught
      immature females on a stopover site in southeast Sweden, and translocated a group
      of them ca. 1,000 km to southern Germany. We followed the movements of the ducks
      via satellite GPS-tracking and observed their migration decisions during the fall
      and consecutive spring migration. The control animals released in Ottenby behaved
      as expected from banding recoveries: they continued migration during the winter
      and in spring returned to the population's breeding grounds in the Baltics and
      Northwest Russia. Contrary to the control animals, the translocated mallards did
      not continue migration and stayed at Lake Constance. In spring, three types of
      movement tactics could be observed: 61.5% of the ducks (16 of 26) stayed around
      Lake Constance, 27% (7 of 26) migrated in a northerly direction towards Sweden
      and 11.5% of the individuals (3 of 26) headed east for ca. 1,000 km and then
      north. We suggest that young female mallards flexibly adjust their migration
      tactics and develop a navigational map that allows them to return to their natal
      breeding area. 

PMID- 24023630
TI  - PhagoSight: an open-source MATLAB(r) package for the analysis of fluorescent
      neutrophil and macrophage migration in a zebrafish model.
AB  - Neutrophil migration in zebrafish larvae is increasingly used as a model to study
      the response of these leukocytes to different determinants of the cellular
      inflammatory response. However, it remains challenging to extract comprehensive
      information describing the behaviour of neutrophils from the multi-dimensional
      data sets acquired with widefield or confocal microscopes. Here, we describe
      PhagoSight, an open-source software package for the segmentation, tracking and
      visualisation of migrating phagocytes in three dimensions. The algorithms in
      PhagoSight extract a large number of measurements that summarise the behaviour of
      neutrophils, but that could potentially be applied to any moving fluorescent
      cells. To derive a useful panel of variables quantifying aspects of neutrophil
      migratory behaviour, and to demonstrate the utility of PhagoSight, we evaluated
      changes in the volume of migrating neutrophils. Cell volume increased as
      neutrophils migrated towards the wound region of injured zebrafish. PhagoSight is
      openly available as MATLAB(r) m-files under the GNU General Public License.
      Synthetic data sets and a comprehensive user manual are available from
      http://www.phagosight.org. 

PMID- 24023631
TI  - MHC-I affects infection intensity but not infection status with a frequent avian
      malaria parasite in blue tits.
AB  - Host resistance against parasites depends on three aspects: the ability to
      prevent, control and clear infections. In vertebrates the immune system consists
      of innate and adaptive immunity. Innate immunity is particularly important for
      preventing infection and eradicating established infections at an early stage
      while adaptive immunity is slow, but powerful, and essential for controlling
      infection intensities and eventually clearing infections. Major
      Histocompatibility Complex (MHC) molecules are central in adaptive immunity, and
      studies on parasite resistance and MHC in wild animals have found effects on both
      infection intensity (parasite load) and infection status (infected or not). It
      seems MHC can affect both the ability to control infection intensities and the
      ability to clear infections. However, these two aspects have rarely been
      considered simultaneously, and their relative importance in natural populations
      is therefore unclear. Here we investigate if MHC class I genotype affects
      infection intensity and infection status with a frequent avian malaria infection
      Haemoproteus majoris in a natural population of blue tits Cyanistes caeruleus. We
      found a significant negative association between a single MHC allele and
      infection intensity but no association with infection status. Blue tits that
      carry a specific MHC allele seem able to suppress H. majoris infection intensity,
      while we have no evidence that this allele also has an effect on clearance of the
      H. majoris infection, a result that is in contrast with some previous studies of
      MHC and avian malaria. A likely explanation could be that the clearance rate of
      avian malaria parasites differs between avian malaria lineages and/or between
      avian hosts.

PMID- 24023632
TI  - Characterization and comparative analyses of muscle transcriptomes in Dorper and
      small-tailed Han sheep using RNA-Seq technique.
AB  - The sheep is an important domestic animal and model for many types of medically
      relevant research. An investigation of gene expression in ovine muscle would
      significantly advance our understanding of muscle growth. RNA-seq is a recently
      developed analytical approach for transcriptome profiling via high-throughput
      sequencing. Although RNA-seq has been recently applied to a wide variety of
      organisms, few RNA-seq studies have been conducted in livestock, particularly in
      sheep. In this study, two cDNA libraries were constructed from the biceps brachii
      of one Small-tailed Han sheep (SH) and one Dorper sheep (DP). The Illumina high
      throughput sequencing technique and bioinformatics were used to determine
      transcript abundances and characteristics. For the SH and DP libraries, we
      obtained a total of 50,264,608 and 52,794,216 high quality reads, respectively.
      Approximately two-thirds of the reads could be mapped to the sheep genome. In
      addition, 40,481 and 38,851 potential coding single nucleotide polymorphisms
      (cSNPs) were observed, respectively, of which a total of 59,139 cSNP coordinates
      were different between the two samples. Up to 5,116 and 5,265 respective
      reference genes had undergone 13,827 and 15,684 alternative splicing events. A
      total of 6,989 reference genes were extended at the 5', 3' or both ends, and
      123,678 novel transcript units were found. A total of 1,300 significantly
      differentially expressed genes were identified between the two libraries. These
      results suggest that there are many differences in the muscle transcriptomes
      between these two animals. This study addresses a preliminary analysis and offers
      a foundation for future genomic research in the sheep. 

PMID- 24023633
TI  - Differential inhibition of ex-vivo tumor kinase activity by vemurafenib in
      BRAF(V600E) and BRAF wild-type metastatic malignant melanoma.
AB  - BACKGROUND: Treatment of metastatic malignant melanoma patients harboring
      BRAF(V600E) has improved drastically after the discovery of the BRAF inhibitor,
      vemurafenib. However, drug resistance is a recurring problem, and prognoses are
      still very bad for patients harboring BRAF wild-type. Better markers for targeted
      therapy are therefore urgently needed. METHODOLOGY: In this study, we assessed
      the individual kinase activity profiles in 26 tumor samples obtained from
      patients with metastatic malignant melanoma using peptide arrays with 144 kinase
      substrates. In addition, we studied the overall ex-vivo inhibitory effects of
      vemurafenib and sunitinib on kinase activity status. RESULTS: Overall kinase
      activity was significantly higher in lysates from melanoma tumors compared to
      normal skin tissue. Furthermore, ex-vivo incubation with both vemurafenib and
      sunitinib caused significant decrease in phosphorylation of kinase substrates,
      i.e kinase activity. While basal phosphorylation profiles were similar in BRAF
      wild-type and BRAF(V600E) tumors, analysis with ex-vivo vemurafenib treatment
      identified a subset of 40 kinase substrates showing stronger inhibition in
      BRAF(V600E) tumor lysates, distinguishing the BRAF wild-type and BRAF(V600E)
      tumors. Interestingly, a few BRAF wild-type tumors showed inhibition profiles
      similar to BRAF(V600E) tumors. The kinase inhibitory effect of vemurafenib was
      subsequently analyzed in cell lines harboring different BRAF mutational status
      with various vemurafenib sensitivity in-vitro. CONCLUSIONS: Our findings suggest
      that multiplex kinase substrate array analysis give valuable information about
      overall tumor kinase activity. Furthermore, intra-assay exposure to kinase
      inhibiting drugs may provide a useful tool to study mechanisms of resistance, as
      well as to identify predictive markers.

PMID- 24023634
TI  - Shared brain lateralization patterns in language and Acheulean stone tool
      production: a functional transcranial Doppler ultrasound study.
AB  - BACKGROUND: The popular theory that complex tool-making and language co-evolved
      in the human lineage rests on the hypothesis that both skills share underlying
      brain processes and systems. However, language and stone tool-making have so far
      only been studied separately using a range of neuroimaging techniques and diverse
      paradigms. METHODOLOGY/PRINCIPAL FINDINGS: We present the first-ever study of
      brain activation that directly compares active Acheulean tool-making and
      language. Using functional transcranial Doppler ultrasonography (fTCD), we
      measured brain blood flow lateralization patterns (hemodynamics) in subjects who
      performed two tasks designed to isolate the planning component of Acheulean stone
      tool-making and cued word generation as a language task. We show highly
      correlated hemodynamics in the initial 10 seconds of task execution.
      CONCLUSIONS/SIGNIFICANCE: Stone tool-making and cued word generation cause common
      cerebral blood flow lateralization signatures in our participants. This is
      consistent with a shared neural substrate for prehistoric stone tool-making and
      language, and is compatible with language evolution theories that posit a co
      evolution of language and manual praxis. In turn, our results support the
      hypothesis that aspects of language might have emerged as early as 1.75 million
      years ago, with the start of Acheulean technology.

PMID- 24023635
TI  - Engineered mitochondrial ferritin as a magnetic resonance imaging reporter in
      mouse olfactory epithelium.
AB  - We report the design of a MRI reporter gene with applications to non-invasive
      molecular imaging. We modified mitochondrial ferritin to localize to the cell
      cytoplasm. We confirmed the efficient cellular processing of this engineered
      protein and demonstrated high iron loading in mammalian cells. The reporter's
      intracellular localization appears as distinct clusters that deliver robust MRI
      contrast. We used this new reporter to image in vivo and ex vivo the gene
      expression in native olfactory sensory neurons in the mouse epithelium. This
      robust MRI reporter can facilitate the study of the molecular mechanisms of
      olfaction and to monitor intranasal gene therapy delivery, as well as a wide
      range of cell tracking and gene expression studies in living subjects. 

PMID- 24023636
TI  - Using spatial analysis to predict health care use at the local level: a case
      study of type 2 diabetes medication use and its association with demographic
      change and socioeconomic status.
AB  - Local health status and health care use may be negatively influenced by low local
      socio-economic profile, population decline and population ageing. To support the
      need for targeted local health care, we explored spatial patterns of type 2
      diabetes mellitus (T2DM) drug use at local level and determined its association
      with local demographic, socio-economic and access to care variables. We assessed
      spatial variability in these associations. We estimated the five-year prevalence
      of T2DM drug use (2005-2009) in persons aged 45 years and older at four-digit
      postal code level using the University of Groningen pharmacy database IADB.nl.
      Statistics Netherlands supplied data on potential predictor variables. We
      assessed spatial clustering, correlations and estimated a multiple linear
      regression model and a geographically weighted regression (GWR) model. Prevalence
      of T2DM medicine use ranged from 2.0% to 25.4%. The regression model included the
      extent of population ageing, proportion of social welfare/benefits, proportion of
      low incomes and proportion of pensioners, all significant positive predictors of
      local T2DM drug use. The GWR model demonstrated considerable spatial variability
      in the association between T2DM drug use and above predictors and was more
      accurate. The findings demonstrate the added value of spatial analysis in
      predicting health care use at local level. 

PMID- 24023637
TI  - Gender-specific effects of genetic variants within Th1 and Th17 cell-mediated
      immune response genes on the risk of developing rheumatoid arthritis.
AB  - The present study was conducted to explore whether single nucleotide
      polymorphisms (SNPs) in Th1 and Th17 cell-mediated immune response genes
      differentially influence the risk of rheumatoid arthritis (RA) in women and men.
      In phase one, 27 functional/tagging polymorphisms in C-type lectins and MCP
      1/CCR2 axis were genotyped in 458 RA patients and 512 controls. Carriers of
      Dectin-2 rs4264222T allele had an increased risk of RA (OR = 1.47, 95%CI 1.10
      1.96) whereas patients harboring the DC-SIGN rs4804803G, MCP-1 rs1024611G, MCP-1
      rs13900T and MCP-1 rs4586C alleles had a decreased risk of developing the disease
      (OR = 0.66, 95%CI 0.49-0.88; OR = 0.66, 95%CI 0.50-0.89; OR = 0.73, 95%CI 0.55
      0.97 and OR = 0.68, 95%CI 0.51-0.91). Interestingly, significant gender-specific
      differences were observed for Dectin-2 rs4264222 and Dectin-2 rs7134303: women
      carrying the Dectin-2 rs4264222T and Dectin-2 rs7134303G alleles had an increased
      risk of RA (OR = 1.93, 95%CI 1.34-2.79 and OR = 1.90, 95%CI 1.29-2.80). Also five
      other SNPs showed significant associations only with one gender: women carrying
      the MCP-1 rs1024611G, MCP-1 rs13900T and MCP-1 rs4586C alleles had a decreased
      risk of RA (OR = 0.61, 95%CI 0.43-0.87; OR = 0.67, 95%CI 0.47-0.95 and OR = 0.60,
      95%CI 0.42-0.86). In men, carriers of the DC-SIGN rs2287886A allele had an
      increased risk of RA (OR = 1.70, 95%CI 1.03-2.78), whereas carriers of the DC
      SIGN rs4804803G had a decreased risk of developing the disease (OR = 0.53, 95%CI
      0.32-0.89). In phase 2, we genotyped these SNPs in 754 RA patients and 519
      controls, leading to consistent gender-specific associations for Dectin-2
      rs4264222, MCP-1 rs1024611, MCP-1 rs13900 and DC-SIGN rs4804803 polymorphisms in
      the pooled sample (OR = 1.38, 95%CI 1.08-1.77; OR = 0.74, 95%CI 0.58-0.94; OR =
      0.76, 95%CI 0.59-0.97 and OR = 0.56, 95%CI 0.34-0.93). SNP-SNP interaction
      analysis of significant SNPs also showed a significant two-locus interaction
      model in women that was not seen in men. This model consisted of Dectin-2
      rs4264222 and Dectin-2 rs7134303 SNPs and suggested a synergistic effect between
      the variants. These findings suggest that Dectin-2, MCP-1 and DC-SIGN
      polymorphisms may, at least in part, account for gender-associated differences in
      susceptibility to RA. 

PMID- 24023639
TI  - Estimation of wheat agronomic parameters using new spectral indices.
AB  - Crop agronomic parameters (leaf area index (LAI), nitrogen (N) uptake, total
      chlorophyll (Chl) content ) are very important for the prediction of crop growth.
      The objective of this experiment was to investigate whether the wheat LAI, N
      uptake, and total Chl content could be accurately predicted using spectral
      indices collected at different stages of wheat growth. Firstly, the product of
      the optimized soil-adjusted vegetation index and wheat biomass dry weight
      (OSAVI*BDW) were used to estimate LAI, N uptake, and total Chl content; secondly,
      BDW was replaced by spectral indices to establish new spectral indices
      (OSAVI*OSAVI, OSAVI*SIPI, OSAVI*CIred edge, OSAVI*CIgreen mode and OSAVI*EVI2);
      finally, we used the new spectral indices for estimating LAI, N uptake, and total
      Chl content. The results showed that the new spectral indices could be used to
      accurately estimate LAI, N uptake, and total Chl content. The highest R(2) and
      the lowest RMSEs were 0.711 and 0.78 (OSAVI*EVI2), 0.785 and 3.98 g/m(2)
      (OSAVI*CIred edge) and 0.846 and 0.65 g/m(2) (OSAVI*CIred edge) for LAI, nitrogen
      uptake and total Chl content, respectively. The new spectral indices performed
      better than the OSAVI alone, and the problems of a lack of sensitivity at earlier
      growth stages and saturation at later growth stages, which are typically
      associated with the OSAVI, were improved. The overall results indicated that this
      new spectral indices provided the best approximation for the estimation of
      agronomic indices for all growth stages of wheat. 

PMID- 24023638
TI  - A meta-analysis of reference values of leptin concentration in healthy
      postmenopausal women.
AB  - OBJECTIVE: There are numerous reports about the leptin concentration (LC) in
      postmenopausal women (PW). Changes in LC can elicit different clinical outcomes.
      We systematically analyzed the LC in PW. METHODS: A search was conducted in
      original English-language studies published from 1994 to October 2012 in the
      following databases: Medline (78), Cochrane Center (123) Embase (505), Biological
      abstracts (108), Cochrane (53) and Science Finder Scholar (0). A meta-analysis
      was undertaken on the correction coefficient (r) between the serum LC and body
      mass index (BMI) for healthy PW across studies containing a dataset and sample
      size. Pre-analytical and analytical variations were examined. Pre-analytical
      variables included fasting status (FS) and sampling timing. Analytical variation
      comprised assay methodology, LC in those undertaking hormone replacement therapy
      (HRT) and those not having HRT as well as LC change according to age. RESULTS:
      Twenty-seven studies met the inclusion criteria. Eighteen studies detected LC in
      the morning in a FS, 15 studies denoted the r between leptin and the BMI. A
      combined r was counted for the 15 studies (r = 0.51 [95% confidence interval
      (CI), 0.46-0.54], P = 0.025), and if sampling collection was in the FSat morning,
      a combined r was form 10 studies (r = 0.54 [95% CI, 0.45-0.54], P = 0.299) and
      heterogeneity was diminished. LC did not change between HRT users and non-users
      in 7 studies. Five studies analyzed changes in LC according to age. CONCLUSION:
      Based on all studies that investigated both LC and BMI, LC was positively
      correlated with the BMI. No studies established reference ranges according to the
      Clinical and Laboratory Standards Institute (CLSI) in healthy PW, and there was a
      wide variation in LC values. These differences suggest that caution should be
      used in the interpretation and comparison between studies.

PMID- 24023640
TI  - Effect of CGRP-adenoviral vector transduction on the osteoblastic differentiation
      of rat adipose-derived stem cells.
AB  - Calcitonin gene-related peptide (CGRP) promotes osteoblast recruitment and
      osteogenic activity. However, no evidence suggests that CGRP could affect the
      differentiation of stem cells toward osteoblasts. In this study, we genetically
      modified adipose-derived stem cells (ADSCs) by introducing the CGRP gene through
      adenoviral vector transduction and investigated on cellular proliferation and
      osteoblast differentiation in vitro and osteogenesis in vivo as well. For the in
      vitro analyses, rat ADSCs were transducted with adenoviral vectors containing the
      CGRP gene (Ad-CGRP) and were cultured in complete osteoblastic medium. The
      morphology, proliferative capacity, and formation of localized regions of
      mineralization in the cells were evaluated. The expression of alkaline
      phosphatase (ALP) and special markers of osteoblasts, such as Collagen I,
      Osteocalcin (BPG) and Osteopontin (OPN), were measured by cytochemistry, MMT, RT
      PCR, and Western blot. For the in vivo analyses, the Ad-CGRP-ADSCs/Beta
      tricalcium phosphate (beta-TCP) constructs were implanted in rat radial bone
      defects for 12 weeks. Radiography and histomorphology evaluations were carried
      out on 4 weeks and 12 weeks. Our analyses indicated that heterogeneous spindle
      shaped cells and localized regions of mineralization were formed in the CGRP
      transduced ADSCs (the transduced group). A higher level of cellular
      proliferation, a high expression level of ALP on days 7 and 14 (p<0.05), and
      increased expression levels of Collagen I, BPG and OPN presented in transduced
      group (p<0.05). The efficiency of new bone formation was dramatically enhanced in
      vivo in Ad-CGRP-ADSCs/beta-TCP group but not in beta-TCP group and ADSCs/beta-TCP
      group. Our results reveal that ADSCs transduced with an Ad-CGRP vector have
      stronger potential to differentiate into osteoblasts in vitro and are able to
      regenerate a promising new tissue engineering bone in vivo. Our findings suggest
      that CGRP-transduced ADSCs may serve as seed cells for bone tissue engineering
      and provide a potential way for treating bone defects. 

PMID- 24023641
TI  - The relationship between gene isoform multiplicity, number of exons and protein
      divergence.
AB  - At present we know that phenotypic differences between organisms arise from a
      variety of sources, like protein sequence divergence, regulatory sequence
      divergence, alternative splicing, etc. However, we do not have yet a complete
      view of how these sources are related. Here we address this problem, studying the
      relationship between protein divergence and the ability of genes to express
      multiple isoforms. We used three genome-wide datasets of human-mouse orthologs to
      study the relationship between isoform multiplicity co-occurrence between
      orthologs (the fact that two orthologs have more than one isoform) and protein
      divergence. In all cases our results showed that there was a monotonic dependence
      between these two properties. We could explain this relationship in terms of a
      more fundamental one, between exon number of the largest isoform and protein
      divergence. We found that this last relationship was present, although with
      variations, in other species (chimpanzee, cow, rat, chicken, zebrafish and fruit
      fly). In summary, we have identified a relationship between protein divergence
      and isoform multiplicity co-occurrence and explained its origin in terms of a
      simple gene-level property. Finally, we discuss the biological implications of
      these findings for our understanding of inter-species phenotypic differences. 

PMID- 24023642
TI  - A novel CXCL10-based GPI-anchored fusion protein as adjuvant in NK-based tumor
      therapy.
AB  - BACKGROUND: Cellular therapy is a promising therapeutic strategy for malignant
      diseases. The efficacy of this therapy can be limited by poor infiltration of the
      tumor by immune effector cells. In particular, NK cell infiltration is often
      reduced relative to T cells. A novel class of fusion proteins was designed to
      enhance the recruitment of specific leukocyte subsets based on their expression
      of a given chemokine receptor. The proteins are composed of an N-terminal
      chemokine head, the mucin domain taken from the membrane-anchored chemokine
      CX3CL1, and a C-terminal glycosylphosphatidylinositol (GPI) membrane anchor
      replacing the normal transmembrane domain allowing integration of the proteins
      into cell membranes when injected into a solid tumor. The mucin domain in
      conjunction with the chemokine head acts to specifically recruit leukocytes
      expressing the corresponding chemokine receptor. METHODOLOGY/PRINCIPAL FINDINGS:
      A fusion protein comprising a CXCL10 chemokine head (CXCL10-mucin-GPI) was used
      for proof of concept for this approach and expressed constitutively in Chinese
      Hamster Ovary cells. FPLC was used to purify proteins. The recombinant proteins
      efficiently integrated into cell membranes in a process dependent upon the GPI
      anchor and were able to activate the CXCR3 receptor on lymphocytes. Endothelial
      cells incubated with CXCL10-mucin-GPI efficiently recruited NK cells in vitro
      under conditions of physiologic flow, which was shown to be dependent on the
      presence of the mucin domain. Experiments conducted in vivo using established
      tumors in mice suggested a positive effect of CXCL10-mucin-GPI on the recruitment
      of NK cells. CONCLUSIONS: The results suggest enhanced recruitment of NK cells by
      CXCL10-mucin-GPI. This class of fusion proteins represents a novel adjuvant in
      cellular immunotherapy. The underlying concept of a chemokine head fused to the
      mucin domain and a GPI anchor signal sequence may be expanded into a broader
      family of reagents that will allow targeted recruitment of cells in various
      settings.

PMID- 24023643
TI  - Vaccination directed against the human endogenous retrovirus-K envelope protein
      inhibits tumor growth in a murine model system.
AB  - Human endogenous retrovirus (HERV) genomes are chromosomally integrated in all
      cells of an individual. They are normally transcriptionally silenced and
      transmitted only vertically. Enhanced expression of HERV-K accompanied by the
      emergence of anti-HERV-K-directed immune responses has been observed in tumor
      patients and HIV-infected individuals. As HERV-K is usually not expressed and
      immunological tolerance development is unlikely, it is an appropriate target for
      the development of immunotherapies. We generated a recombinant vaccinia virus
      (MVA-HKenv) expressing the HERV-K envelope glycoprotein (ENV), based on the
      modified vaccinia virus Ankara (MVA), and established an animal model to test its
      vaccination efficacy. Murine renal carcinoma cells (Renca) were genetically
      altered to express E. coli beta-galactosidase (RLZ cells) or the HERV-K ENV gene
      (RLZ-HKenv cells). Intravenous injection of RLZ-HKenv cells into syngenic BALB/c
      mice led to the formation of pulmonary metastases, which were detectable by X-gal
      staining. A single vaccination of tumor-bearing mice with MVA-HKenv drastically
      reduced the number of pulmonary RLZ-HKenv tumor nodules compared to vaccination
      with wild-type MVA. Prophylactic vaccination of mice with MVA-HKenv precluded the
      formation of RLZ-HKenv tumor nodules, whereas wild-type MVA-vaccinated animals
      succumbed to metastasis. Protection from tumor formation correlated with enhanced
      HERV-K ENV-specific killing activity of splenocytes. These data demonstrate for
      the first time that HERV-K ENV is a useful target for vaccine development and
      might offer new treatment opportunities for diverse types of cancer. 

PMID- 24023645
TI  - Increased systemic and local interleukin 9 levels in patients with carotid and
      coronary atherosclerosis.
AB  - OBJECTIVE: Atherosclerosis is a chronic inflammatory disorder that involves a
      range of inflammatory mediators. Although interleukin (IL)-9 has been related to
      inflammation, there are at present no data on its role in atherosclerosis. Here
      we have examined IL-9 and IL-9 receptor (IL-9R) systemically and locally in
      patients with coronary and carotid atherosclerosis. METHODS: Plasma IL-9 was
      quantified by enzyme immunoassay and multiplex technology. IL-9 and IL-9R mRNA
      were quantified by real-time RT-PCR, and their localization within the lesion was
      assessed by immunohistochemistry. RESULTS: THE MAIN FINDINGS WERE: (i) Patients
      with carotid atherosclerosis had significantly raised IL-9 plasma levels compared
      with healthy controls (n = 28), with no differences between asymptomatic (n = 56)
      and symptomatic (n = 88) patients. (ii) On admission, patients with acute ST
      elevation myocardial infarction (STEMI) (n = 42) had markedly raised IL-9 plasma
      levels which gradually declined during the first week post-MI. (iii) T cells and
      monocytes from patients with unstable angina (n = 17) had increased mRNA levels
      of IL-9 as compared with controls (n = 11). (iv) Carotid plaques (n = 68) showed
      increased mRNA levels of IL-9 and IL-9R compared to non-atherosclerotic vessels
      (n = 10). Co-localization to T cells (IL-9 and IL-9R) and macrophages (IL-9) were
      shown by immunohistochemistry. (v) IL-9 increased IL-17 release in peripheral
      blood mononuclear cells from patients with unstable angina (n = 5) and healthy
      controls (n = 5) with a particularly enhancing effect in cells from the patient
      group. CONCLUSION: Our findings show increased IL-9 levels in different
      atherosclerotic disorders both systemically and within the lesion, suggesting a
      role for the IL-9/IL-9R axis in the atherosclerotic process, potentially
      involving IL-17 mediated mechanisms. However, the functional consequences of
      these findings should be further investigated.

PMID- 24023644
TI  - Demyelination in mild cognitive impairment suggests progression path to
      Alzheimer's disease.
AB  - The preclinical Alzheimer's disease (AD) - amnestic mild cognitive impairment
      (MCI) - is manifested by phenotypes classified into exclusively memory (single
      domain) MCI (sMCI) and multiple-domain MCI (mMCI). We suggest that typical MCI-to
      AD progression occurs through the sMCI-to-mMCI sequence as a result of the
      extension of initial pathological processes. To support this hypothesis, we
      assess myelin content with a Magnetization Transfer Ratio (MTR) in 21 sMCI and 21
      mMCI patients and in 42 age-, sex-, and education-matched controls. A conjunction
      analysis revealed MTR reduction shared by sMCI and mMCI groups in the medial
      temporal lobe and posterior structures including white matter (WM: splenium,
      posterior corona radiata) and gray matter (GM: hippocampus; parahippocampal and
      lingual gyri). A disjunction analysis showed the spread of demyelination to
      prefrontal WM and insula GM in executive mMCI. Our findings suggest that
      demyelination starts in the structures affected by neurofibrillary pathology; its
      presence correlates with the clinical picture and indicates the method of MCI-to
      AD progression. In vivo staging of preclinical AD can be developed in terms of
      WM/GM demyelination. 

PMID- 24023647
TI  - Correction of diabetic erectile dysfunction with adipose derived stem cells
      modified with the vascular endothelial growth factor gene in a rodent diabetic
      model.
AB  - The aim of this study was to determine whether adipose derived stem cells (ADSCs)
      expressing vascular endothelial growth factor (VEGF) gene can improve endothelial
      function, recover the impaired VEGF signaling pathway and enhance smooth muscle
      contents in a rat diabetic erectile dysfunction (DED) model. DED rats were
      induced via intraperitoneal injection of streptozotocin (40 mg/kg), and then
      screened by apomorphine (100 ug/kg). Five groups were used (n = 12/group)-Group 1
      (G1): intracavernous injection of lentivirus-VEGF; G2: ADSCs injection; G3: VEGF
      expressing ADSCs injection; G4: Phosphate buffered saline injection; G1-G4 were
      DED rats; G5: normal rats. The mean arterial pressure (MAP) and intracavernosal
      pressure (ICP) were measured at days 7 and 28 after the injections. The
      components of the VEGF system, endothelial, smooth muscle, pericytes markers in
      cavernoursal tissue were assessed. On day 28 after injection, the group with
      intracavernosum injection of ADSCs expressing VEGF displayed more efficiently and
      significantly raised ICP and ICP/MAP (p<0.01) than those with ADSCs or lentivirus
      VEGF injection. Western blot and immunofluorescent analysis demonstrated that
      improved erectile function by ADSCs-VEGF was associated with increased expression
      of endothelial markers (VEGF, VEGF R1, VEGF R2, eNOS, CD31 and vWF), smooth
      muscle markers (a-actin and smoothelin), and pericyte markers (CD146 and NG2).
      ADSCs expressing VEGF produced a therapeutic effect and restored erectile
      function in diabetic rats by enhancing VEGF-stimulated endothelial function and
      increasing the contents of smooth muscle and pericytes. 

PMID- 24023646
TI  - Chronic HIV infection enhances the responsiveness of antigen presenting cells to
      commensal Lactobacillus.
AB  - Chronic immune activation despite long-term therapy poses an obstacle to immune
      recovery in HIV infection. The role of antigen presenting cells (APCs) in chronic
      immune activation during HIV infection remains to be fully determined. APCs, the
      frontline of immune defense against pathogens, are capable of distinguishing
      between pathogens and non-pathogenic, commensal bacteria. We hypothesized that
      HIV infection induces dysfunction in APC immune recognition and response to some
      commensal bacteria and that this may promote chronic immune activation. Therefore
      we examined APC inflammatory cytokine responses to commensal lactobacilli. We
      found that APCs from HIV-infected patients produced an enhanced inflammatory
      response to Lactobacillus plantarum WCFS1 as compared to APCs from healthy, HIV
      negative controls. Increased APC expression of TLR2 and CD36, signaling through
      p38-MAPK, and decreased expression of MAP kinase phosphatase-1 (MKP-1) in HIV
      infection was associated with this heightened immune response. Our findings
      suggest that chronic HIV infection enhances the responsiveness of APCs to
      commensal lactobacilli, a mechanism that may partly contribute to chronic immune
      activation. 

PMID- 24023648
TI  - Effect of concomitant administration of L-glutamine and cycloart-23-ene-3beta, 25
      diol (B2) with sitagliptin in GLP-1 (7-36) amide secretion, biochemical and
      oxidative stress in streptozotocin - nicotinamide induced diabetic Sprague Dawley
      rats.
AB  - Previously we have reported that, cycloart-23-ene-3beta, 25-diol (called as B2)
      and L-glutamine stimulated glucagon like peptide-1 (GLP-1) (7-36) amide secretion
      diabetic rats. The objective of present investigation was to investigate the
      concomitant administration of cycloart-23-ene-3beta, 25-diol+sitagliptin and L
      glutamine+sitagliptin in streptozotocin - nicotinamide induced diabetic Sprague
      Dawley. Type 2 diabetes was induced in overnight fasted male Sprague Dawley rats
      pre-treated with nicotinamide (100 mg/kg, i.p.) followed by administration of
      streptozotocin (55 mg/kg, i.p.) 20 min after. The rats were divided into; I- non
      diabetic, II- diabetic control, III- Sitagliptin (5 mg/kg, p.o.)+cycloart-23-ene
      3beta, 25-diol (1 mg/kg, p.o.), IV- Sitagliptin (5 mg/kg, p.o.)+L-glutamine (1000
      mg/kg, p.o.). The concomitant treatment of cycloart-23-ene-3beta, 25-diol and L
      glutamine with sitagliptin was 8 weeks. Plasma glucose, body weight, food and
      water intake were determined every week. Glycosylated haemoglobin, lipid profile,
      plasma and colonic active (GLP-1) (7-36) amide, plasma and pancreatic insulin,
      histology of pancreata and biomarkers of oxidative stress were measured after
      8(th) week treatment. Concomitant administration of cycloart-23-ene-3beta, 25
      diol and L-glutamine with sitagliptin significantly (p<0.001) reduced plasma
      glucose, glyoxylated haemoglobin, lipid profile and oxidative stress parameters
      compared to diabetic control groups. Both concomitant treatment increased plasma
      and pancreatic insulin as well as plasma and colonic active (GLP-1) (7-36) amide
      secretion. Histological analysis by Gomori staining observed less destruction of
      pancreatic beta cells. The result obtained from this study; it is concluded that
      concomitant administration of cycloart-23-ene-3beta, 25-diol+sitagliptin and L
      glutamine+sitagliptin showed additive antihyperglycaemic effect in diabetic rats.

PMID- 24023649
TI  - Dependence of brain intravoxel incoherent motion perfusion parameters on the
      cardiac cycle.
AB  - Measurement of microvascular perfusion with Intravoxel Incoherent Motion (IVIM)
      MRI is gaining interest. Yet, the physiological influences on the IVIM perfusion
      parameters ("pseudo-diffusion" coefficient D*, perfusion fraction f, and flow
      related parameter fD*) remain insufficiently characterized. In this article, we
      hypothesize that D* and fD*, which depend on blood speed, should vary during the
      cardiac cycle. We extended the IVIM model to include time dependence of D* =
      D*(t), and demonstrate in the healthy human brain that both parameters D* and fD*
      are significantly larger during systole than diastole, while the diffusion
      coefficient D and f do not vary significantly. The results non-invasively
      demonstrate the pulsatility of the brain's microvasculature. 

PMID- 24023650
TI  - Valence and arousal ratings for 420 Finnish nouns by age and gender.
AB  - Language-and culture-specific norms are needed for research on emotion-laden
      stimuli. We present valence and arousal ratings for 420 Finnish nouns for a
      sample of 996 Finnish speakers. Ratings are provided both for the whole sample
      and for subgroups divided by age and gender in light of previous research
      suggesting age- and gender-specific reactivity to the emotional content in
      stimuli. Moreover, corpus-based frequency values and word length are provided as
      objective psycholinguistic measures of the nouns. The relationship between
      valence and arousal mainly showed the curvilinear relationship reported in
      previous studies. Age and gender effects on valence and arousal ratings were
      statistically significant but weak. The inherent affective properties of the
      words in terms of mean valence and arousal ratings explained more of the variance
      in the ratings. In all, the findings suggest that language- and culture-related
      factors influence the way affective properties of words are rated to a greater
      degree than demographic factors. This database will provide researchers with
      normative data for Finnish emotion-laden and emotionally neutral words. The
      normative database is available in Database S1. 

PMID- 24023651
TI  - The gap between estimated incidence of end-stage renal disease and use of
      therapy.
AB  - BACKGROUND: Relatively few data exist on the burden of end-stage renal disease
      (ESRD) and use of renal replacement therapy (RRT)-a life-saving therapy-in
      developing regions. No study has quantified the proportion of patients who
      develop ESRD but are unable to access RRT. METHODS: We performed a comprehensive
      literature search to estimate use and annual initiation of RRT worldwide, and
      present these estimates according to World Bank regions. We also present
      estimates of survival and of etiology of diseases in patients undergoing RRT.
      Using data on prevalence of diabetes and hypertension, we modeled the incidence
      of ESRD related to these risk factors in order to quantify the gap between ESRD
      and use of RRT in developing regions. RESULTS: We find that 1.9 million patients
      are undergoing RRT worldwide, with continued use and annual initiation at 316 and
      73 per million population respectively. RRT use correlates directly (Pearson's r
      = 0.94) with regional income. Hemodialysis remains the dominant form of RRT but
      there is wide regional variation in its use. With the exception of the Latin
      American and Caribbean region, it appears that initiation of RRT in developing
      regions is restricted to fewer than a quarter of patients projected to develop
      ESRD. This results in at least 1.2 million premature deaths each year due to lack
      of access to RRT as a result of diabetes and elevated blood pressure and as many
      as 3.2 million premature deaths due to all causes of ESRD. CONCLUSION: Thus, the
      majority of patients projected to reach ESRD due to diabetes or hypertension in
      developing regions are unable to access RRT; this gap will increase with rising
      prevalence of these risk factors worldwide.

PMID- 24023652
TI  - Concentrations of the stress hormone copeptin increase upon hypoglycaemia in
      patients with type 1 diabetes dependent of hypoglycaemia awareness.
AB  - OBJECTIVE: Copeptin, a marker for stress mirroring vasopressin concentrations,
      has been shown to increase upon insulin-induced hypoglycaemia in patients after
      transsphenoidal surgery of pituitary adenomas. Patients with type 1 diabetes
      mellitus are prone to hypoglycaemia, but no data about copeptin levels upon
      hypoglycaemia are available. Furthermore, the perception of hypoglycaemia can
      vary from total unawareness to disabling episodes. The aim of this study was to
      investigate whether copeptin increases upon hypoglycaemia in patients with type 1
      diabetes mellitus and is associated with the degree of hypoglycaemia awareness.
      MATERIALS AND METHODS: In this prospective observational study, 17 patients with
      type 1 diabetes underwent a standardized insulin infusion test. Blood sampling
      for glucose and copeptin was performed at baseline and after 60 minutes (min). To
      assess hypoglycaemia associated symptoms the Mood and Symptom Questionnaire (MSQ)
      was conducted at baseline and after 60 min. RESULTS: During insulin infusion,
      blood glucose decreased from 5.1 (SD+/-0.2) to 3.0 (+/-0.5) mmol/L at 60 min
      (p<0.001). Copeptin concentrations increased from 3.2 (+/-1.7) to 3.8 (+/-1.9)
      pmol/L (p = 0.03). Mood and Symptoms Questionnaire scores increased from 14 (+/
      3.0) to 18 (+/-5.8), (p = 0.006). Patients with good hypoglycaemia awareness had
      an increase in copeptin from 3.0 (+/-1.8) to 4.2 (+/-2.4) pmol/L (p = 0.03) in
      contrast to patients more unaware of hypoglycaemia who only showed an increase in
      copeptin from 3.3 (+/-1.6) to 3.6 (+/-1.4) pmol/L (p = 0.4). There was a trend to
      a larger copeptin increase in patients aware of hypoglycemia compared to patients
      unaware of hypoglycemia (p = 0.074). CONCLUSION: Copeptin increases in patients
      with type 1 diabetes upon insulin induced hypoglycaemia. Interestingly, the
      copeptin increase seems associated with the degree of hypoglycaemia awareness.
      This hypothesis warrants further verification. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00515801.

PMID- 24023654
TI  - A new look on protein-polyphenol complexation during honey storage: is this a
      random or organized event with the help of dirigent-like proteins?
AB  - Honey storage initiates melanoidin formation that involves a cascade of seemingly
      unguided redox reactions between amino acids/proteins, reducing sugars and
      polyphenols. In the process, high molecular weight protein-polyphenol complexes
      are formed, but the mechanism involved remains unknown. The objective of this
      study was twofold: to determine quantitative and qualitative changes in proteins
      in honeys stored for prolonged times and in different temperatures and to relate
      these changes to the formation of protein-polyphenol complexes. Six -month
      storage decreased the protein content by 46.7% in all tested honeys (t-test,
      p<0.002) with the rapid reduction occurring during the first three month. The
      changes in protein levels coincided with alterations in molecular size and net
      charge of proteins on SDS -PAGE. Electro-blotted proteins reacted with a quinone
      specific nitro blue tetrazolium (NBT) on nitrocellulose membranes indicating that
      quinones derived from oxidized polyphenols formed covalent bonds with proteins.
      Protein-polyphenol complexes isolated by size-exclusion chromatography differed
      in size and stoichiometry and fall into two categories: (a) high molecular weight
      complexes (230-180 kDa) enriched in proteins but possessing a limited reducing
      activity toward the NBT and (b) lower molecular size complexes (110-85 kDa)
      enriched in polyphenols but strongly reducing the dye. The variable stoichiometry
      suggest that the large, "protein-type" complexes were formed by protein cross
      linking, while in the smaller, "polyphenol-type" complexes polyphenols were first
      polymerized prior to protein binding. Quinones preferentially bound a 31 kDa
      protein which, by the electrospray quadrupole time of flight mass spectrometry
      (ESI-Qtof-MS) analysis, showed homology to dirigent-like proteins known for
      assisting in radical coupling and polymerization of phenolic compounds. These
      findings provide a new look on protein-polyphenol interaction in honey where the
      reaction of quinones with proteins and polyphenols could possibly be under
      assumed guidance of dirigent proteins. 

PMID- 24023655
TI  - An analytic study on the effect of alginate on the velocity profiles of blood in
      rectangular microchannels using microparticle image velocimetry.
AB  - It is desired to understand the effect of alginic acid sodium salt from brown
      algae (alginate) as a viscosity modifier on the behavior of blood in vitro using
      a micro-particle image velocimetry (uPIV) system. The effect of alginate on the
      shape of the velocity profile, the flow rate and the maximum velocity achieved in
      rectangular microchannels channels are measured. The channels were constructed of
      polydimethylsiloxane (PDMS), a biocompatible silicone. Porcine blood cells
      suspended in saline was used as the working fluid at twenty percent hematocrit (H
      = 20). While alginate was only found to have minimal effect on the maximum
      velocity and the flow rate achieved, it was found to significantly affect the
      shear rate at the wall by between eight to a hundred percent. 

PMID- 24023653
TI  - Caveolae regulation of mechanosensitive channel function in myotubes.
AB  - Mutations that lead to muscular dystrophy often create deficiencies in
      cytoskeletal support of the muscle sarcolemma causing hyperactive
      mechanosensitive cation channel (MSC) activity and elevated intracellular Ca(2+).
      Caveolae are cholesterol-rich microdomains that form mechanically deformable
      invaginations of the sarcolemma. Mutations to caveolin-3, the main scaffolding
      protein of caveolae in muscle, cause Limbe-Girdle muscular dystrophy. Using
      genetic and acute chemical perturbations of developing myotubes we investigated
      whether caveolae are functionally linked to MSCs. MSC sensitivity was assayed
      using suction application to patches and probe-induced indentation during whole
      cell recordings. Membrane mechanical stress in patches was monitored using patch
      capacitance/impedance. Cholesterol depletion disrupted caveolae and caused a
      large increase in MSC current. It also decreased the membrane mechanical
      relaxation time, likely reflecting cytoskeleton dissociation from the bilayer.
      Reduction of Cav3 expression with miRNA also increased MSC current and decreased
      patch relaxation time. In contrast Cav3 overexpression produced a small decrease
      in MSC currents. To acutely and specifically inhibit Cav3 interactions, we made a
      chimeric peptide containing the antennapedia membrane translocation domain and
      the Cav3 scaffolding domain (A-CSD3). A-CSD3 action was time dependent initially
      producing a mild Ca(2+) leak and increased MSC current, while longer exposures
      decreased MSC currents coinciding with increased patch stiffening. Images of GFP
      labeled Cav3 in patches showed that Cav3 doesn't enter the pipette, showing patch
      composition differed from the cell surface. However, disruption via cholesterol
      depletion caused Cav3 to become uniformly distributed over the sarcolemma and
      Cav3 appearance in the patch dome. The whole-cell indentation currents elicited
      under the different caveolae modifying conditions mirror the patch response
      supporting the role of caveolae in MSC function. These studies show that normal
      expression levels of Cav3 are mechanoprotective to the sarcolemma through
      multiple mechanisms, and Cav3 upregulation observed in some dystrophies may
      compensate for other mechanical deficiencies. 

PMID- 24023656
TI  - Identification and survey of a novel avian coronavirus in ducks.
AB  - The rapid discovery of novel viruses using next generation sequencing (NGS)
      technologies including DNA-Seq and RNA-Seq, has greatly expanded our
      understanding of viral diversity in recent years. The timely identification of
      novel viruses using NGS technologies is also important for us to control emerging
      infectious diseases caused by novel viruses. In this study, we identified a novel
      duck coronavirus (CoV), distinct with chicken infectious bronchitis virus (IBV),
      using RNA-Seq. The novel duck-specific CoV was a potential novel species within
      the genus Gammacoronavirus, as indicated by sequences of three regions in the
      viral 1b gene. We also performed a survey of CoVs in domestic fowls in China
      using reverse-transcription polymerase chain reaction (RT-PCR), targeting the
      viral nucleocapsid (N) gene. A total of 102 CoV positives were identified through
      the survey. Phylogenetic analysis of the viral N sequences suggested that CoVs in
      domestic fowls have diverged into several region-specific or host-specific clades
      or subclades in the world, and IBVs can infect ducks, geese and pigeons, although
      they mainly circulate in chickens. Moreover, this study provided novel data
      supporting the notion that some host-specific CoVs other than IBVs circulate in
      ducks, geese and pigeons, and indicated that the novel duck-specific CoV
      identified through RNA-Seq in this study is genetically closer to some CoVs
      circulating in wild water fowls. Taken together, this study shed new insight into
      the diversity, distribution, evolution and control of avian CoVs. 

PMID- 24023658
TI  - Leukemia prediction using sparse logistic regression.
AB  - We describe a supervised prediction method for diagnosis of acute myeloid
      leukemia (AML) from patient samples based on flow cytometry measurements. We use
      a data driven approach with machine learning methods to train a computational
      model that takes in flow cytometry measurements from a single patient and gives a
      confidence score of the patient being AML-positive. Our solution is based on an
      [Formula: see text] regularized logistic regression model that aggregates AML
      test statistics calculated from individual test tubes with different cell
      populations and fluorescent markers. The model construction is entirely data
      driven and no prior biological knowledge is used. The described solution scored a
      100% classification accuracy in the DREAM6/FlowCAP2 Molecular Classification of
      Acute Myeloid Leukaemia Challenge against a golden standard consisting of 20 AML
      positive and 160 healthy patients. Here we perform a more extensive validation of
      the prediction model performance and further improve and simplify our original
      method showing that statistically equal results can be obtained by using simple
      average marker intensities as features in the logistic regression model. In
      addition to the logistic regression based model, we also present other
      classification models and compare their performance quantitatively. The key
      benefit in our prediction method compared to other solutions with similar
      performance is that our model only uses a small fraction of the flow cytometry
      measurements making our solution highly economical. 

PMID- 24023657
TI  - Induction of porcine host defense peptide gene expression by short-chain fatty
      acids and their analogs.
AB  - Dietary modulation of the synthesis of endogenous host defense peptides (HDPs)
      represents a novel antimicrobial approach for disease control and prevention,
      particularly against antibiotic-resistant infections. However, HDP regulation by
      dietary compounds such as butyrate is species-dependent. To examine whether
      butyrate could induce HDP expression in pigs, we evaluated the expressions of a
      panel of porcine HDPs in IPEC-J2 intestinal epithelial cells, 3D4/31 macrophages,
      and primary monocytes in response to sodium butyrate treatment by real-time PCR.
      We revealed that butyrate is a potent inducer of multiple, but not all, HDP
      genes. Porcine beta-defensin 2 (pBD2), pBD3, epididymis protein 2 splicing
      variant C (pEP2C), and protegrins were induced markedly in response to butyrate,
      whereas pBD1 expression remained largely unaltered in any cell type.
      Additionally, a comparison of the HDP-inducing efficacy among saturated free
      fatty acids of different aliphatic chain lengths revealed that fatty acids
      containing 3-8 carbons showed an obvious induction of HDP expression in IPEC-J2
      cells, with butyrate being the most potent and long-chain fatty acids having only
      a marginal effect. We further investigated a panel of butyrate analogs for their
      efficacy in HDP induction, and found glyceryl tributyrate, benzyl butyrate, and 4
      phenylbutyrate to be comparable with butyrate. Identification of butyrate and
      several analogs with a strong capacity to induce HDP gene expression in pigs
      provides attractive candidates for further evaluation of their potential as novel
      alternatives to antibiotics in augmenting innate immunity and disease resistance
      of pigs. 

PMID- 24023659
TI  - Differential sensitivity of bat cells to infection by enveloped RNA viruses:
      coronaviruses, paramyxoviruses, filoviruses, and influenza viruses.
AB  - Bats (Chiroptera) host major human pathogenic viruses including corona-,
      paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from
      either Yinpterochiroptera (including African flying foxes and a rhinolophid bat)
      or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection
      by different enveloped RNA viruses. None of the cells were sensitive to infection
      by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to
      infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV)
      incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The
      resistance to infection was overcome if cells were transfected to express the
      respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin
      converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of
      two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six
      tested bat cell lines. By contrast, viral pseudotypes containing the surface
      protein GP of Marburg virus from the family Filoviridae infected all six cell
      lines though at different efficiency. Notably, all cells were sensitive to
      infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial
      virus) and three influenza viruses from different subtypes. These results
      indicate that bat cells are more resistant to infection by coronaviruses than to
      infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore,
      these results show a receptor-dependent restriction of the infection of bat cells
      by CoV. The implications for the isolation of coronaviruses from bats are
      discussed. 

PMID- 24023660
TI  - Whole transcriptome analysis of Acinetobacter baumannii assessed by RNA
      sequencing reveals different mRNA expression profiles in biofilm compared to
      planktonic cells.
AB  - Acinetobacterbaumannii has emerged as a dangerous opportunistic pathogen, with
      many strains able to form biofilms and thus cause persistent infections. The aim
      of the present study was to use high-throughput sequencing techniques to
      establish complete transcriptome profiles of planktonic (free-living) and sessile
      (biofilm) forms of A. baumannii ATCC 17978 and thereby identify differences in
      their gene expression patterns. Collections of mRNA from planktonic (both
      exponential and stationary phase cultures) and sessile (biofilm) cells were
      sequenced. Six mRNA libraries were prepared following the mRNA-Seq protocols from
      Illumina. Reads were obtained in a HiScanSQ platform and mapped against the
      complete genome to describe the complete mRNA transcriptomes of planktonic and
      sessile cells. The results showed that the gene expression pattern of A.
      baumannii biofilm cells was distinct from that of planktonic cells, including
      1621 genes over-expressed in biofilms relative to stationary phase cells and 55
      genes expressed only in biofilms. These differences suggested important changes
      in amino acid and fatty acid metabolism, motility, active transport, DNA
      methylation, iron acquisition, transcriptional regulation, and quorum sensing,
      among other processes. Disruption or deletion of five of these genes caused a
      significant decrease in biofilm formation ability in the corresponding mutant
      strains. Among the genes over-expressed in biofilm cells were those in an operon
      involved in quorum sensing. One of them, encoding an acyl carrier protein, was
      shown to be involved in biofilm formation as demonstrated by the significant
      decrease in biofilm formation by the corresponding knockout strain. The present
      work serves as a basis for future studies examining the complex network systems
      that regulate bacterial biofilm formation and maintenance. 

PMID- 24023662
TI  - Building development and roads: implications for the distribution of stone
      curlews across the Brecks.
AB  - BACKGROUND: Substantial new housing and infrastructure development planned within
      England has the potential to conflict with the nature conservation interests of
      protected sites. The Breckland area of eastern England (the Brecks) is designated
      as a Special Protection Area for a number of bird species, including the stone
      curlew (for which it holds more than 60% of the UK total population). We explore
      the effect of buildings and roads on the spatial distribution of stone curlew
      nests across the Brecks in order to inform strategic development plans to avoid
      adverse effects on such European protected sites. METHODOLOGY: Using data across
      all years (and subsets of years) over the period 1988-2006 but restricted to
      habitat areas of arable land with suitable soils, we assessed nest density in
      relation to the distances to nearest settlements and to major roads. Measures of
      the local density of nearby buildings, roads and traffic levels were assessed
      using normal kernel distance-weighting functions. Quasi-Poisson generalised
      linear mixed models allowing for spatial auto-correlation were fitted. RESULTS:
      Significantly lower densities of stone curlew nests were found at distances up to
      1500m from settlements, and distances up to 1000m or more from major (trunk)
      roads. The best fitting models involved optimally distance-weighted variables for
      the extent of nearby buildings and the trunk road traffic levels. SIGNIFICANCE:
      The results and predictions from this study of past data suggests there is cause
      for concern that future housing development and associated road infrastructure
      within the Breckland area could have negative impacts on the nesting stone curlew
      population. Given the strict legal protection afforded to the SPA the planning
      and conservation bodies have subsequently agreed precautionary restrictions on
      building development within the distances identified and used the modelling
      predictions to agree mitigation measures for proposed trunk road developments.

PMID- 24023661
TI  - Sex workers perspectives on strategies to reduce sexual exploitation and HIV
      risk: a qualitative study in Tijuana, Mexico.
AB  - Globally, female sex workers are a population at greatly elevated risk of HIV
      infection, and the reasons for and context of sex industry involvement have key
      implications for HIV risk and prevention. Evidence suggests that experiences of
      sexual exploitation (i.e., forced/coerced sex exchange) contribute to health
      related harms. However, public health interventions that address HIV
      vulnerability and sexual exploitation are lacking. Therefore, the objective of
      this study was to elicit recommendations for interventions to prevent sexual
      exploitation and reduce HIV risk from current female sex workers with a history
      of sexual exploitation or youth sex work. From 2010-2011, we conducted in-depth
      interviews with sex workers (n = 31) in Tijuana, Mexico who reported having
      previously experienced sexual exploitation or youth sex work. Participants
      recommended that interventions aim to (1) reduce susceptibility to sexual
      exploitation by providing social support and peer-based education; (2) mitigate
      harms by improving access to HIV prevention resources and psychological support,
      and reducing gender-based violence; and (3) provide opportunities to exit the sex
      industry via vocational supports and improved access to effective drug treatment.
      Structural interventions incorporating these strategies are recommended to reduce
      susceptibility to sexual exploitation and enhance capacities to prevent HIV
      infection among marginalized women and girls in Mexico and across international
      settings. 

PMID- 24023663
TI  - Sympatric breeding auks shift between dietary and spatial resource partitioning
      across the annual cycle.
AB  - When species competing for the same resources coexist, some segregation in the
      way they utilize those resources is expected. However, little is known about how
      closely related sympatric breeding species segregate outside the breeding season.
      We investigated the annual segregation of three closely related seabirds
      (razorbill Alcatorda, common guillemot Uriaaalge and Brunnich's guillemot U.
      lomvia) breeding at the same colony in Southwest Greenland. By combining GPS and
      geolocation (GLS) tracking with dive depth and stable isotope analyses, we
      compared spatial and dietary resource partitioning. During the breeding season,
      we found the three species to segregate in diet and/or dive depth, but less in
      foraging area. During both the post-breeding and pre-breeding periods, the three
      species had an increased overlap in diet, but were dispersed over a larger
      spatial scale. Dive depths were similar across the annual cycle, suggesting
      morphological adaptations fixed by evolution. Prey choice, on the other hand,
      seemed much more flexible and therefore more likely to be affected by the
      immediate presence of potential competitors. 

PMID- 24023664
TI  - Testing agents for prevention or reversal of type 1 diabetes in rodents.
AB  - We report the results of an independent laboratory's tests of novel agents to
      prevent or reverse type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse,
      BioBreeding diabetes prone (BBDP) rat, and multiple autoimmune disease prone
      (MAD) rat models. Methods were developed to better mimic human clinical trials,
      including: prescreening, randomization, blinding, and improved glycemic care of
      the animals. Agents were suggested by the research community in an open call for
      proposals, and selected for testing by an NIDDK appointed independent review
      panel. Agents selected for testing to prevent diabetes at later stages of
      progression in a rodent model were a STAT4 antagonist (DT22669), alpha1 anti
      trypsin (Aralast NP), celastrol (a natural product with anti-inflammatory
      properties), and a Macrophage Inflammatory Factor inhibitor (ISO-092). Agents
      tested for reversal of established T1D in rodent models were: alpha1 anti-trypsin
      (Aralast NP), tolerogenic peptides (Tregitopes), and a long-acting formulation of
      GLP-1 (PGC-GLP-1). None of these agents were seen to prevent or reverse type 1
      diabetes, while the positive control interventions were effective: anti-CD3
      treatment provided disease reversal in the NOD mouse, dexamethasone prevented T1D
      induction in the MAD rat, and cyclosporin prevented T1D in the BBDP rat. For some
      tested agents, details of previous formulation, delivery, or dosing, as well as
      laboratory procedure, availability of reagents and experimental design, could
      have impacted our ability to confirm prior reports of efficacy in preclinical
      animal models. In addition, the testing protocols utilized here provided
      detection of effects in a range commonly used in placebo controlled clinical
      trials (for example, 50% effect size), and thus may have been underpowered to
      observe more limited effects. That said, we believe the results compiled here,
      showing good control and repeatability, confirm the feasibility of screening
      diverse test agents in an independent laboratory. 

PMID- 24023665
TI  - Proteomic changes between male and female worms of the polychaetous annelid
      Neanthes arenaceodentata before and after spawning.
AB  - The Neanthesacuminata species complex (Polychaeta) are cosmopolitan in
      distribution. Neanthesarenaceodentata, Southern California member of the N.
      acuminata complex, has been widely used as toxicological test animal in the
      marine environment. Method of reproduction is unique in this polychaete complex.
      Same sexes fight and opposite sexes lie side by side until egg laying. Females
      lose about 75% of their weight and die after laying eggs. The male, capable of
      reproducing up to nine times, fertilizes the eggs and incubates the embryos for 3
      4 weeks. The objective of this study was to determine if there is any set of
      proteins that influences this unique pattern of reproduction. Gel-based two
      dimensional electrophoresis (2-DE) and gel-free quantitative proteomics methods
      were used to identify differential protein expression patterns before and after
      spawning in both male and female N. arenaceodentata. Males showed a higher degree
      of similarity in protein expression patterns but females showed large changes in
      phosphoproteme before and after spawning. There was a decrease (about 70%) in the
      number of detected phosphoproteins in spent females. The proteins involved in
      muscular development, cell signaling, structure and integrity, and translation
      were differentially expressed. This study provides proteomic insights of the male
      and female worms that may serve as a foundation for better understanding of
      unusual reproductive patterns in polychaete worms. 

PMID- 24023667
TI  - The incidence and relative risk of stroke among patients with bipolar disorder: a
      seven-year follow-up study.
AB  - OBJECTIVE: This study aimed to estimate the incidence and relative risk of stroke
      and post-stroke all-cause mortality among patients with bipolar disorder.
      METHODS: This study identified a study population from the National Health
      Insurance Research Database (NHIRD) between 1999 and 2003 that included 16,821
      patients with bipolar disorder and 67,284 age- and sex-matched control
      participants without bipolar disorder. The participants who had experienced a
      stroke between 1999 and 2003 were excluded and were randomly selected from the
      NHIRD. The incidence of stroke (ICD-9-CM code 430-438) and patient survival after
      stroke were calculated for both groups using data from the NIHRD between 2004 and
      2010. A Cox proportional-hazards model was used to compare the seven-year stroke
      free survival rate and all-cause mortality rate across the two cohorts after
      adjusting for confounding risk factors. RESULTS: A total of 472 (2.81%) patients
      with bipolar disorder and 1,443 (2.14%) controls had strokes over seven years.
      Patients with bipolar disorder were 1.24 times more likely to have a stroke (95%
      CI = 1.12-1.38; p<0.0001) after adjusting for demographic characteristics and
      comorbid medical conditions. In addition, 513 (26.8%) patients who had a stroke
      died during the follow-up period. The all-cause mortality hazard ratio for
      patients with bipolar disorder was 1.28 (95% CI = 1.06-1.55; p = 0.012) after
      adjusting for patient, physician and hospital variables. CONCLUSIONS: The
      likelihood of developing a stroke was greater among patients with bipolar
      disorder than controls, and the all-cause mortality rate was higher among
      patients with bipolar disorder than controls during a seven-year follow-up
      period.

PMID- 24023666
TI  - Characterization of epiphytic bacterial communities from grapes, leaves, bark and
      soil of grapevine plants grown, and their relations.
AB  - Despite its importance in plant health and crop quality, the diversity of
      epiphytic bacteria on grape berries and other plant parts, like leaves and bark,
      remains poorly described, as does the role of telluric bacteria in plant
      colonization. In this study, we compare the bacterial community size and
      structure in vineyard soils, as well as on grapevine bark, leaves and berries.
      Analyses of culturable bacteria revealed differences in the size and structure of
      the populations in each ecosystem. The highest bacteria population counts and the
      greatest diversity of genera were found in soil samples, followed by bark, grapes
      and leaves. The identification of isolates revealed that some genera -
      Pseudomonas, Curtobacterium, and Bacillus - were present in all ecosystems, but
      in different amounts, while others were ecosystem-specific. About 50% of the
      genera were common to soil and bark, but absent from leaves and grapes. The
      opposite was also observed: grape and leaf samples presented 50% of genera in
      common that were absent from trunk and soil. The bacterial community structure
      analyzed by T-RFLP indicated similarities between the profiles of leaves and
      grapes, on the one hand, and bark and soil, on the other, reflecting the number
      of shared T-RFs. The results suggest an interaction between telluric bacterial
      communities and the epiphytic bacteria present on the different grapevine parts. 

PMID- 24023668
TI  - Inhibition of oxidative stress-elicited AKT activation facilitates PPARgamma
      agonist-mediated inhibition of stem cell character and tumor growth of liver
      cancer cells.
AB  - Emerging evidence suggests that tumor-initiating cells (TICs) are the most
      malignant cell subpopulation in tumors because of their resistance to
      chemotherapy or radiation treatment. Targeting TICs may be a key innovation for
      cancer treatment. In this study, we found that PPARgamma agonists inhibited the
      cancer stem cell-like phenotype and attenuated tumor growth of human
      hepatocellular carcinoma (HCC) cells. Reactive oxygen species (ROS) initiated by
      NOX2 upregulation were partially responsible for the inhibitory effects mediated
      by PPARgamma agonists. However, PPARgamma agonist-mediated ROS production
      significantly activated AKT, which in turn promoted TIC survival by limiting ROS
      generation. Inhibition of AKT, by either pharmacological inhibitors or AKT siRNA,
      significantly enhanced PPARgamma agonist-mediated inhibition of cell
      proliferation and stem cell-like properties in HCC cells. Importantly, in nude
      mice inoculated with HCC Huh7 cells, we demonstrated a synergistic inhibitory
      effect of the PPARgamma agonist rosiglitazone and the AKT inhibitor triciribine
      on tumor growth. In conclusion, we observed a negative feedback loop between
      oxidative stress and AKT hyperactivation in PPARgamma agonist-mediated
      suppressive effects on HCCs. Combinatory application of an AKT inhibitor and a
      PPARgamma agonist may provide a new strategy for inhibition of stem cell-like
      properties in HCCs and treatment of liver cancer. 

PMID- 24023669
TI  - Hyperthyroidism and risk for bipolar disorders: a nationwide population-based
      study.
AB  - BACKGROUND: Thyroid disorders have long been associated with psychiatric illness,
      often with symptoms suggestive of mood disorders. The most common clinical
      features associated with hyperthyroidism are anxiety and depression. The risk of
      bipolar disorders, especially bipolar mania, among patients with thyroid
      disorders has not been well characterized. OBJECTIVE: We explored the
      relationship of hyperthyroidism and the subsequent development of bipolar
      disorders, and examined the risk factors for bipolar disorders in patients with
      hyperthyroidism. METHODS: We identified patients who were diagnosed with
      hyperthyroidism between 2000 and 2010 in the Taiwan National Health Insurance
      Research Database. A comparison cohort without hyperthyroidism was matched based
      on age, sex, and comorbidities. The occurrence of bipolar disorders was evaluated
      in both cohorts based on diagnosis and the use of mood stabilizer drugs. RESULTS:
      The hyperthyroidism cohort consisted of 21, 574 patients, and the comparison
      cohort consisted of 21, 574 matched control patients without hyperthyroidism. The
      incidence of bipolar disorders (incidence rate ratio [IRR], 2.31, 95% CI 1.80
      2.99, P<.001) was higher for the hyperthyroidism patients than the control
      patients. Multivariate, matched regression models showed that women (HR 2.02, 95%
      CI 1.34-3.05, P = .001), patients with alcohol use disorders (HR 3.03, 95% CI
      1.58-5.79, P = .001), and those with asthma (HR 1.70, 95% CI 1.18-2.43, P = .004)
      were independent risk factors for the development of bipolar disorders in
      hyperthyroidism patients. CONCLUSIONS: Although a possibility that the diagnosis
      of bipolar disorders in this study actually includes "bipolar disorders due to
      hyperthyroidism" cannot be excluded, this study suggests that hyperthyroidism may
      increase the risk of developing bipolar disorders.

PMID- 24023670
TI  - Is upregulation of BCL2 a determinant of tumor development driven by inactivation
      of CDH1/E-cadherin?
AB  - Inactivation of CDH1, encoding E-cadherin, promotes cancer initiation and
      progression. According to a newly proposed molecular mechanism, loss of E
      cadherin triggers an upregulation of the anti-apoptotic oncoprotein BCL2.
      Conversely, reconstitution of E-cadherin counteracts overexpression of BCL2. This
      reciprocal regulation is thought to be critical for early tumor development. We
      determined the relevance of this new concept in human infiltrating lobular breast
      cancer (ILBC), the prime tumor entity associated with CDH1 inactivation. BCL2
      expression was examined in human ILBC cell lines (IPH-926, MDA-MB-134, SUM-44)
      harboring deleterious CDH1 mutations. To test for an intact regulatory axis
      between E-cadherin and BCL2, wild-type E-cadherin was reconstituted in ILBC cells
      by ectopic expression. Moreover, BCL2 and E-cadherin were evaluated in primary
      invasive breast cancers and in synchronous lobular carcinomas in situ (LCIS). MDA
      MB-134 and IPH-926 showed little or no BCL2 expression, while SUM-44 ILBC cells
      were BCL2-positive. Reconstitution of E-cadherin failed to impact on BCL2
      expression in all cell lines tested. Primary ILBCs were almost uniformly E
      cadherin-negative (97%) and were frequently BCL2-negative (46%). When compared
      with an appropriate control group, ILBCs showed a trend towards an increased
      frequency of BCL2-negative cases (P = 0.064). In terminal duct-lobular units
      affected by LCIS, the E-cadherin-negative neoplastic component showed a similar
      or a reduced BCL2-immunoreactivity, when compared with the adjacent epithelium.
      In conclusion, upregulation of BCL2 is not involved in lobular breast
      carcinogenesis and is unlikely to represent an important determinant of tumor
      development driven by CDH1 inactivation. 

PMID- 24023671
TI  - The role of autophagy in chloroplast degradation and chlorophagy in immune
      defenses during Pst DC3000 (AvrRps4) infection.
AB  - BACKGROUND: Chlorosis of leaf tissue normally observed during pathogen infection
      may result from the degradation of chloroplasts. There is a growing evidence to
      suggest that the chloroplast plays a significant role during pathogen infection.
      Although most degradation of the organelles and cellular structures in plants is
      mediated by autophagy, its role in chloroplast catabolism during pathogen
      infection is largely unknown. RESULTS: In this study, we investigated the
      function of autophagy in chloroplast degradation during avirulent Pst DC3000
      (AvrRps4) infection. We examined the expression of defensive marker genes and
      suppression of bacterial growth using the electrolyte leakage assay in normal
      light (N) and low light (L) growing environments of wild-type and atg5-1 plants
      during pathogen treatment. Stroma-targeted GFP proteins (CT-GFP) were observed
      with LysoTracker Red (LTR) staining of autophagosome-like structures in the
      vacuole. The results showed that Arabidopsis expressed a significant number of
      small GFP-labeled bodies when infected with avirulent Pst DC3000 (AvrRps4). While
      barely detectable, there were small GFP-labeled bodies in plants with the CT-GFP
      expressing atg5-1 mutation. The results showed that chloroplast degradation
      depends on autophagy and this may play an important role in inhibiting pathogen
      growth. CONCLUSION: Autophagy plays a role in chloroplast degradation in
      Arabidopsis during avirulent Pst DC3000 (AvrRps4) infection. Autophagy dependent
      chloroplast degradation may be the primary source of reactive oxygen species
      (ROS) as well as the pathogen-response signaling molecules that induce the
      defense response.

PMID- 24023672
TI  - Resveratrol as a pan-HDAC inhibitor alters the acetylation status of histone
      [corrected] proteins in human-derived hepatoblastoma cells.
AB  - The polyphenolic alcohol resveratrol has demonstrated promising activities for
      the prevention and treatment of cancer. Different modes of action have been
      described for resveratrol including the activation of sirtuins, which represent
      the class III histone deacetylases (HDACs). However, little is known about the
      activity of resveratrol on the classical HDACs of class I, II and IV, although
      these classes are involved in cancer development or progression and inhibitors of
      HDACs (HDACi) are currently under investigation as promising novel anticancer
      drugs. We could show by in silico docking studies that resveratrol has the
      chemical structure to inhibit the activity of different human HDAC enzymes. In
      vitro analyses of overall HDAC inhibition and a detailed HDAC profiling showed
      that resveratrol inhibited all eleven human HDACs of class I, II and IV in a dose
      dependent manner. Transferring this molecular mechanism into cancer therapy
      strategies, resveratrol treatment was analyzed on solid tumor cell lines. Despite
      the fact that hepatocellular carcinoma (HCC) is known to be particularly
      resistant against conventional chemotherapeutics, treatment of HCC with
      established HDACi already has shown promising results. Testing of resveratrol on
      hepatoma cell lines HepG2, Hep3B and HuH7 revealed a dose-dependent
      antiproliferative effect on all cell lines. Interestingly, only for HepG2 cells a
      specific inhibition of HDACs and in turn a histone hyperacetylation caused by
      resveratrol was detected. Additional testing of human blood samples demonstrated
      a HDACi activity by resveratrol ex vivo. Concluding toxicity studies showed that
      primary human hepatocytes tolerated resveratrol, whereas in vivo chicken
      embryotoxicity assays demonstrated severe toxicity at high concentrations. Taken
      together, this novel pan-HDACi activity opens up a new perspective of resveratrol
      for cancer therapy alone or in combination with other chemotherapeutics.
      Moreover, resveratrol may serve as a lead structure for chemical optimization of
      bioavailability, pharmacology or HDAC inhibition. 

PMID- 24023673
TI  - Rapid learning of magnetic compass direction by C57BL/6 mice in a 4-armed 'plus'
      water maze.
AB  - Magnetoreception has been demonstrated in all five vertebrate classes. In
      rodents, nest building experiments have shown the use of magnetic cues by two
      families of molerats, Siberian hamsters and C57BL/6 mice. However, assays widely
      used to study rodent spatial cognition (e.g. water maze, radial arm maze) have
      failed to provide evidence for the use of magnetic cues. Here we show that
      C57BL/6 mice can learn the magnetic direction of a submerged platform in a 4
      armed (plus) water maze. Naive mice were given two brief training trials. In each
      trial, a mouse was confined to one arm of the maze with the submerged platform at
      the outer end in a predetermined alignment relative to magnetic north. Between
      trials, the training arm and magnetic field were rotated by 180( degrees ) so
      that the mouse had to swim in the same magnetic direction to reach the submerged
      platform. The directional preference of each mouse was tested once in one of four
      magnetic field alignments by releasing it at the center of the maze with access
      to all four arms. Equal numbers of responses were obtained from mice tested in
      the four symmetrical magnetic field alignments. Findings show that two training
      trials are sufficient for mice to learn the magnetic direction of the submerged
      platform in a plus water maze. The success of these experiments may be explained
      by: (1) absence of alternative directional cues (2), rotation of magnetic field
      alignment, and (3) electromagnetic shielding to minimize radio frequency
      interference that has been shown to interfere with magnetic compass orientation
      of birds. These findings confirm that mice have a well-developed magnetic
      compass, and give further impetus to the question of whether epigeic rodents
      (e.g., mice and rats) have a photoreceptor-based magnetic compass similar to that
      found in amphibians and migratory birds. 

PMID- 24023674
TI  - TLR2 regulates neutrophil recruitment and cytokine production with minor
      contributions from TLR9 during hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops
      following repeated exposure to environmental antigens. The disease results in
      alveolitis, granuloma formation and may progress to a fibrotic chronic form,
      which is associated with significant morbidity and mortality. The severity of the
      disease correlates with a neutrophil rich influx and an IL-17 response. We used
      the Saccharopolysporarectivirgula (SR) model of HP to determine whether Toll-like
      receptors (TLR) 2 and 9 cooperate in neutrophil recruitment and IL-17-associated
      cytokine production during the development of HP. Stimulation of bone marrow
      derived macrophages (BMDMs) from C57BL/6, MyD88(-/-) and TLR2/9(-/-) mice with SR
      demonstrate that SR is a strong inducer of neutrophil chemokines and growth
      factors. The cytokines induced by SR were MyD88-dependent and, of those, most
      were partially or completely dependent on TLRs 2 and 9. Following in vivo
      exposure to SR, CXCL2 production and neutrophil recruitment were reduced in TLR2(
      /-) and TLR2/9(-/-) mice suggesting that the response was largely dependent on
      TLR2; however the reduction was greatest in the TLR2/9(-/-) double knockout mice
      indicating TLR9 may also contribute to the response. There was a reduction in the
      levels of pro-inflammatory cytokines TNFalpha and IL-6 as well as CCL3 and CCL4
      in the BALF from TLR2/9(-/-) mice compared to WT and single knockout (SKO) mice
      exposed one time to SR. The decrease in neutrophil recruitment and TNFalpha
      production in the TLR2/9(-/-) mice was maintained throughout 3 weeks of SR
      exposures in comparison to WT and SKO mice. Both TLRs 2 and 9 contributed to the
      Th17 response; there was a decrease in Th17 cells and IL-17 mRNA in the TLR2/9(-/
      ) mice in comparison to the WT and SKO mice. Despite the effects on neutrophil
      recruitment and the IL-17 response, TLR2/9(-/-) mice developed granuloma
      formation similarly to WT and SKO mice suggesting that there are additional
      mediators and pattern recognition receptors involved in the disease. 

PMID- 24023675
TI  - Optimising bait for pitfall trapping of Amazonian dung beetles (Coleoptera:
      Scarabaeinae).
AB  - The accurate sampling of communities is vital to any investigation of ecological
      processes and biodiversity. Dung beetles have emerged as a widely used focal
      taxon in environmental studies and can be sampled quickly and inexpensively using
      baited pitfalls. Although there is now a wealth of available data on dung beetle
      communities from around the world, there is a lack of standardisation between
      sampling protocols for accurately sampling dung beetle communities. In
      particular, bait choice is often led by the idiosyncrasies of the researcher,
      logistic problems and the dung sources available, which leads to difficulties for
      inter-study comparisons. In general, human dung is the preferred choice, however,
      it is often in short supply, which can severely limit sampling effort. By
      contrast, pigs may produce up to 20 times the volume. We tested the ability of
      human and pig dung to attract a primary forest dung beetle assemblage, as well as
      three mixes of the two baits in different proportions. Analyses focussed on the
      comparability of sampling with pig or human-pig dung mixes with studies that have
      sampled using human dung. There were no significant differences between richness
      and abundance sampled by each bait. The assemblages sampled were remarkably
      consistent across baits, and ordination analyses showed that the assemblages
      sampled by mixed dung baits were not significantly different from that captured
      by pure human dung, with the assemblages sampled by 10% and 90% pig mixes
      structurally most similar to assemblages sampled by human dung. We suggest that a
      10:90 human:pig ratio, or similar, is an ideal compromise between sampling
      efficiency, inter-study comparability and the availability of large quantities of
      bait for sampling Amazonian dung beetles. Assessing the comparability of
      assemblage samples collected using different baits represents an important step
      to facilitating large-scale meta-analyses of dung beetle assemblages collected
      using non-standard methodology. 

PMID- 24023676
TI  - Notch signaling limits supporting cell plasticity in the hair cell-damaged early
      postnatal murine cochlea.
AB  - In mammals, auditory hair cells are generated only during embryonic development
      and loss or damage to hair cells is permanent. However, in non-mammalian
      vertebrate species, such as birds, neighboring glia-like supporting cells
      regenerate auditory hair cells by both mitotic and non-mitotic mechanisms. Based
      on work in intact cochlear tissue, it is thought that Notch signaling might
      restrict supporting cell plasticity in the mammalian cochlea. However, it is
      unresolved how Notch signaling functions in the hair cell-damaged cochlea and the
      molecular and cellular changes induced in supporting cells in response to hair
      cell trauma are poorly understood. Here we show that gentamicin-induced hair cell
      loss in early postnatal mouse cochlear tissue induces rapid morphological changes
      in supporting cells, which facilitate the sealing of gaps left by dying hair
      cells. Moreover, we provide evidence that Notch signaling is active in the hair
      cell damaged cochlea and identify Hes1, Hey1, Hey2, HeyL, and Sox2 as targets and
      potential Notch effectors of this hair cell-independent mechanism of Notch
      signaling. Using Cre/loxP based labeling system we demonstrate that inhibition of
      Notch signaling with a gamma- secretase inhibitor (GSI) results in the trans
      differentiation of supporting cells into hair cell-like cells. Moreover, we show
      that these hair cell-like cells, generated by supporting cells have molecular,
      cellular, and basic electrophysiological properties similar to immature hair
      cells rather than supporting cells. Lastly, we show that the vast majority of
      these newly generated hair cell-like cells express the outer hair cell specific
      motor protein prestin. 

PMID- 24023677
TI  - Line orientation adaptation: local or global?
AB  - Prolonged exposure to an oriented line shifts the perceived orientation of a
      subsequently observed line in the opposite direction, a phenomenon known as the
      tilt aftereffect (TAE). Here we consider whether the TAE for line stimuli is
      mediated by a mechanism that integrates the local parts of the line into a single
      global entity prior to the site of adaptation, or the result of the sum of local
      TAEs acting separately on the parts of the line. To test between these two
      alternatives we used the fact the TAE transfers almost completely across
      luminance contrast polarity [1]. We measured the TAE using adaptor and test lines
      that (1) either alternated in luminance polarity or were of a single polarity,
      and (2) either alternated in local orientation or were of a single orientation.
      We reasoned that if the TAE was agnostic to luminance polarity and was parts
      based, we should obtain large TAEs using alternating-polarity adaptors with
      single-polarity tests. However we found that (i) TAEs using one-alternating
      polarity adaptors with all-white tests were relatively small, increased slightly
      for two-alternating-polarity adaptors, and were largest with all-white or all
      black adaptors. (ii) however TAEs were relatively large when the test was one
      alternating polarity, irrespective of the adaptor type. (iii) The results with
      orientation closely mirrored those obtained with polarity with the difference
      that the TAE transfer across orthogonal orientations was weak. Taken together,
      our results demonstrate that the TAE for lines is mediated by a global shape
      mechanism that integrates the parts of lines into whole prior to the site of
      orientation adaptation. The asymmetry in the magnitude of TAE depending on
      whether the alternating-polarity lines was the adaptor or test can be explained
      by an imbalance in the population of neurons sensitive to 1(st)-and 2(nd)-order
      lines, with the 2(nd)-order lines being encoded by a subset of the mechanisms
      sensitive to 1(st)-order lines. 

PMID- 24023678
TI  - Characterization of microRNAs in mud crab Scylla paramamosain under Vibrio
      parahaemolyticus infection.
AB  - BACKGROUND: Infection of bacterial Vibrio parahaemolyticus is common in mud crab
      farms. However, the mechanisms of the crab's response to pathogenic V.
      parahaemolyticus infection are not fully understood. MicroRNAs (miRNAs) are a
      class of small noncoding RNAs that function as regulators of gene expression and
      play essential roles in various biological processes. To understand the
      underlying mechanisms of the molecular immune response of the crab to the
      pathogens, high-throughput Illumina/Solexa deep sequencing technology was used to
      investigate the expression profiles of miRNAs in S. paramamosain under V.
      parahaemolyticus infection. METHODOLOGY/PRINCIPAL FINDINGS: Two mixed RNA pools
      of 7 tissues (intestine, heart, liver, gill, brain, muscle and blood) were
      obtained from V. parahaemolyticus infected crabs and the control groups,
      respectively. By aligning the sequencing data with known miRNAs, we characterized
      421 miRNA families, and 133 conserved miRNA families in mud crab S. paramamosain
      were either identical or very similar to existing miRNAs in miRBase. Stem-loop
      qRT-PCRs were used to scan the expression levels of four randomly chosen
      differentially expressed miRNAs and tissue distribution. Eight novel potential
      miRNAs were confirmed by qRT-PCR analysis and the precursors of these novel
      miRNAs were verified by PCR amplification, cloning and sequencing in S.
      paramamosain. 161 miRNAs (106 of which up-regulated and 55 down-regulated) were
      significantly differentially expressed during the challenge and the potential
      targets of these differentially expressed miRNAs were predicted. Furthermore, we
      demonstrated evolutionary conservation of mud crab miRNAs in the animal evolution
      process. CONCLUSIONS/SIGNIFICANCE: In this study, a large number of miRNAs were
      identified in S. paramamosain when challenged with V. parahaemolyticus, some of
      which were differentially expressed. The results show that miRNAs might play some
      important roles in regulating gene expression in mud crab under V.
      parahaemolyticus infection, providing a basis for further investigation of miRNA
      modulating networks in innate immunity of mud crab.

PMID- 24023679
TI  - Estimating a Markovian epidemic model using household serial interval data from
      the early phase of an epidemic.
AB  - The clinical serial interval of an infectious disease is the time between date of
      symptom onset in an index case and the date of symptom onset in one of its
      secondary cases. It is a quantity which is commonly collected during a pandemic
      and is of fundamental importance to public health policy and mathematical
      modelling. In this paper we present a novel method for calculating the serial
      interval distribution for a Markovian model of household transmission dynamics.
      This allows the use of Bayesian MCMC methods, with explicit evaluation of the
      likelihood, to fit to serial interval data and infer parameters of the underlying
      model. We use simulated and real data to verify the accuracy of our methodology
      and illustrate the importance of accounting for household size. The output of our
      approach can be used to produce posterior distributions of population level
      epidemic characteristics. 

PMID- 24023680
TI  - Synergistic effect of mesangial cell-induced CXCL1 and TGF-beta1 in promoting
      podocyte loss in IgA nephropathy.
AB  - Podocyte loss has been reported to relate to disease severity and progression in
      IgA nephropathy (IgAN). However, the underlying mechanism for its role in IgAN
      remain unclear. Recent evidence has shown that IgA1 complexes from patients with
      IgAN could activate mesangial cells to induce soluble mediator excretion, and
      further injure podocytes through mesangial-podocytic cross-talk. In the present
      study, we explored the underlying mechanism of mesangial cell-induced podocyte
      loss in IgAN. We found that IgA1 complexes from IgAN patients significantly up
      regulated the expression of CXCL1 and TGF-beta1 in mesangial cells compared with
      healthy controls. Significantly higher urinary levels of CXCL1 and TGF-beta1 were
      also observed in patients with IgAN compared to healthy controls. Moreover, IgAN
      patients with higher urinary CXCL1 and TGF-beta1 presented with severe clinical
      and pathological manifestations, including higher 24-hour urine protein
      excretion, lower eGFR and higher cresentic glomeruli proportion. Further in vitro
      experiments showed that increased podocyte death and reduced podocyte adhesion
      were induced by mesangial cell conditional medium from IgAN (IgAN-HMCM), as well
      as rhCXCL1 together with rhTGF-beta1. In addition, the over-expression of CXCR2,
      the receptor for CXCL1, by podocytes was induced by IgAN-HMCM and rhTGF-beta1,
      but not by rhCXCL1. Furthermore, the effect of increased podocyte death and
      reduced podocyte adhesion induced by IgAN-HMCM and rhCXCL1 and rhTGF-beta1 was
      rescued partially by a blocking antibody against CXCR2. Moreover, we observed the
      expression of CXCR2 in urine exfoliated podocytes in IgAN patients. Our present
      study implied that IgA1 complexes from IgAN patients could up-regulate the
      secretion of CXCL1 and TGF-beta1 in mesangial cells. Additionally, the
      synergistic effect of CXCL1 and TGF-beta1 further induced podocyte death and
      adhesion dysfunction in podocytes via CXCR2. This might be a potential mechanism
      for podocyte loss observed in IgAN. 

PMID- 24023681
TI  - Biofortified cassava with pro-vitamin A is sensory and culturally acceptable for
      consumption by primary school children in Kenya.
AB  - BACKGROUND: Biofortification of cassava with pro-vitamin A can potentially reduce
      vitamin A deficiency in low-income countries. However, little is known about
      consumer acceptance of this deep yellow variety of cassava compared to the
      commonly available white varieties. We aimed to determine the sensory and
      cultural acceptability of the consumption of pro-vitamin A rich cassava in order
      to identify key factors predicting the intention to consume pro-vitamin A rich
      cassava by families with school-aged children in Eastern Kenya. METHODS: Sensory
      acceptability was measured by replicated discrimination tests and paired
      preference tests among 30 children (7-12 yr) and 30 caretakers (18-45 yr) in
      three primary schools. Cultural acceptability was assessed with a questionnaire
      based on the combined model of The Theory of Planned Behavior and The Health
      Belief Model in one primary school among 140 caretakers of children aged 6 to 12
      years. Correlations and multivariate analyses were used to determine associations
      between summed scores for model constructs. RESULTS: Caretakers and children
      perceived a significant difference in taste between white and pro-vitamin A rich
      cassava. Both preferred pro-vitamin A rich cassava over white cassava because of
      its soft texture, sweet taste and attractive color. Knowledge about pro-vitamin A
      rich cassava and it's relation to health ('Knowledge' ((beta = 0.29, P = <.01))
      was a strong predictor of 'Health behavior identity'. Worries related to bitter
      taste and color ('Perceived barriers 1' (beta = -0.21, P = .02)), the belief of
      the caretaker about having control to prepare cassava ('Control beliefs' (beta =
      0.18, P = .02)) and activities like information sessions about pro-vitamin A rich
      cassava and recommendations from health workers ('Cues to action'(beta = 0.51, P
      = <.01)) were the best predictors of intention to consume pro-vitamin A rich
      cassava. CONCLUSIONS: Pro-vitamin A rich cassava is well accepted by school
      children in our study population.

PMID- 24023682
TI  - Development of the preterm gut microbiome in twins at risk of necrotising
      enterocolitis and sepsis.
AB  - The preterm gut microbiome is a complex dynamic community influenced by genetic
      and environmental factors and is implicated in the pathogenesis of necrotising
      enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development
      of the gut microbiome in preterm twins to determine how shared environmental and
      genetic factors may influence temporal changes and compared this to the expressed
      breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin
      pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected
      longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel
      electrophoresis) analysis and a selected subset underwent 454 pyrosequencing.
      Stool and EBM shared a core microbiome dominated by Enterobacteriaceae,
      Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater
      similarity between siblings compared to unrelated individuals. Pyrosequencing
      revealed a reduction in diversity and increasing dominance of Escherichia sp.
      preceding NEC that was not observed in the healthy twin. Antibiotic treatment had
      a substantial effect on the gut microbiome, reducing Escherichia sp. and
      increasing other Enterobacteriaceae. This study demonstrates related preterm
      twins share similar gut microbiome development, even within the complex
      environment of neonatal intensive care. This is likely a result of shared genetic
      and immunomodulatory factors as well as exposure to the same maternal microbiome
      during birth, skin contact and exposure to EBM. Environmental factors including
      antibiotic exposure and feeding are additional significant determinants of
      community structure, regardless of host genetics. 

PMID- 24023683
TI  - Validating excised rodent lungs for functional hyperpolarized xenon-129 MRI.
AB  - Ex vivo rodent lung models are explored for physiological measurements of
      respiratory function with hyperpolarized (hp) (129)Xe MRI. It is shown that
      excised lung models allow for simplification of the technical challenges involved
      and provide valuable physiological insights that are not feasible using in vivo
      MRI protocols. A custom designed breathing apparatus enables MR images of gas
      distribution on increasing ventilation volumes of actively inhaled hp (129)Xe.
      Straightforward hp (129)Xe MRI protocols provide residual lung volume (RV) data
      and permit for spatially resolved tracking of small hp (129)Xe probe volumes
      during the inhalation cycle. Hp (129)Xe MRI of lung function in the excised organ
      demonstrates the persistence of post mortem airway responsiveness to intravenous
      methacholine challenges. The presented methodology enables physiology of lung
      function in health and disease without additional regulatory approval
      requirements and reduces the technical and logistical challenges with hp gas MRI
      experiments. The post mortem lung functional data can augment histological
      measurements and should be of interest for drug development studies. 

PMID- 24023684
TI  - CYP2J2 overexpression protects against arrhythmia susceptibility in cardiac
      hypertrophy.
AB  - Maladaptive cardiac hypertrophy predisposes one to arrhythmia and sudden death.
      Cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) promote anti
      inflammatory and antiapoptotic mechanisms, and are involved in the regulation of
      cardiac Ca(2+)-, K(+)- and Na(+)-channels. To test the hypothesis that enhanced
      cardiac EET biosynthesis counteracts hypertrophy-induced electrical remodeling,
      male transgenic mice with cardiomyocyte-specific overexpression of the human
      epoxygenase CYP2J2 (CYP2J2-TG) and wildtype littermates (WT) were subjected to
      chronic pressure overload (transverse aortic constriction, TAC) or beta
      adrenergic stimulation (isoproterenol infusion, ISO). TAC caused progressive
      mortality that was higher in WT (42% over 8 weeks after TAC), compared to CYP2J2
      TG mice (6%). In vivo electrophysiological studies, 4 weeks after TAC, revealed
      high ventricular tachyarrhythmia inducibility in WT (47% of the stimulation
      protocols), but not in CYP2J2-TG mice (0%). CYP2J2 overexpression also enhanced
      ventricular refractoriness and protected against TAC-induced QRS prolongation and
      delocalization of left ventricular connexin-43. ISO for 14 days induced high
      vulnerability for atrial fibrillation in WT mice (54%) that was reduced in CYP-TG
      mice (17%). CYP2J2 overexpression also protected against ISO-induced reduction of
      atrial refractoriness and development of atrial fibrosis. In contrast to these
      profound effects on electrical remodeling, CYP2J2 overexpression only moderately
      reduced TAC-induced cardiac hypertrophy and did not affect the hypertrophic
      response to beta-adrenergic stimulation. These results demonstrate that enhanced
      cardiac EET biosynthesis protects against electrical remodeling, ventricular
      tachyarrhythmia, and atrial fibrillation susceptibility during maladaptive
      cardiac hypertrophy. 

PMID- 24023685
TI  - Bevacizumab attenuates hepatic fibrosis in rats by inhibiting activation of
      hepatic stellate cells.
AB  - Angiogenesis is a fundamental part of the response to tissue injury, which is
      involved in the development of hepatic fibrosis. Vascular endothelial growth
      factor plays an important role in angiogenesis. The expression of VEGF is
      increased during hepatic fibrogenesis and correlates with the micro-vessel
      density. In this study, we investigated the effects of bevacizumab, an anti
      angiogenetic drug, on the formation of hepatic fibrosis. We found that
      bevacizumab could attenuate the development of hepatic fibrosis and contribute to
      the protection of liver function. Bevacizumab was also found to downregulate the
      expression alpha-SMA and TGF-beta1, which have been reported to be profibrogenic
      genes in vivo. We also observed that the expression of VEGF increased
      significantly during the development of hepatic fibrosis and CCl4 was found to
      induce hepatocytes to secrete VEGF, which led to the activation and proliferation
      of HSCs. Bevacizumab was also found to block the effects of the hepatocytes on
      the activation and proliferation of HSCs. Our results suggest that bevacizumab
      might alleviate liver fibrosis by blocking the effect of VEGF on HSCs.
      Bevacizumab might be suitable as a potential agent for hepatic fibrosis therapy. 

PMID- 24023686
TI  - Force spectroscopy measurements show that cortical neurons exposed to excitotoxic
      agonists stiffen before showing evidence of bleb damage.
AB  - In ischemic and traumatic brain injury, hyperactivated glutamate (N-methyl-D
      aspartic acid, NMDA) and sodium (Nav) channels trigger excitotoxic neuron death.
      Na(+), Ca(++) and H2O influx into affected neurons elicits swelling (increased
      cell volume) and pathological blebbing (disassociation of the plasma membrane's
      bilayer from its spectrin-actomyosin matrix). Though usually conflated in injured
      tissue, cell swelling and blebbing are distinct processes. Around an injury core,
      salvageable neurons could be mildly swollen without yet having suffered the bleb
      type membrane damage that, by rendering channels leaky and pumps dysfunctional,
      exacerbates the excitotoxic positive feedback spiral. Recognizing when neuronal
      inflation signifies non-lethal osmotic swelling versus blebbing should further
      efforts to salvage injury-penumbra neurons. To assess whether the mechanical
      properties of osmotically-swollen versus excitotoxically-blebbing neurons might
      be cytomechanically distinguishable, we measured cortical neuron elasticity
      (gauged via atomic force microscopy (AFM)-based force spectroscopy) upon brief
      exposure to hypotonicity or to excitotoxic agonists (glutamate and Nav channel
      activators, NMDA and veratridine). Though unperturbed by solution exchange per
      se, elasticity increased abruptly with hypotonicity, with NMDA and with
      veratridine. Neurons then invariably softened towards or below the pre-treatment
      level, sometimes starting before the washout. The initial channel-mediated
      stiffening bespeaks an abrupt elevation of hydrostatic pressure linked to NMDA or
      Nav channel-mediated ion/H2O fluxes, together with increased [Ca(++)]int-mediated
      submembrane actomyosin contractility. The subsequent softening to below-control
      levels is consistent with the onset of a lethal level of bleb damage. These
      findings indicate that dissection/identification of molecular events during the
      excitotoxic transition from stiff/swollen to soft/blebbing is warranted and
      should be feasible. 

PMID- 24023687
TI  - Mitochondrial uptake of thiamin pyrophosphate: physiological and cell biological
      aspects.
AB  - Mammalian cells obtain vitamin B1 (thiamin) from their surrounding environment
      and convert it to thiamin pyrophosphate (TPP) in the cytoplasm. Most of TPP is
      then transported into the mitochondria via a carrier-mediated process that
      involves the mitochondrial thiamin pyrophosphate transporter (MTPPT). Knowledge
      about the physiological parameters of the MTPP-mediated uptake process, MTPPT
      targeting and the impact of clinical mutations in MTPPT in patients with Amish
      lethal microcephaly and neuropathy and bilateral striatal necrosis are not fully
      elucidated, and thus, were addressed in this study using custom-made (3)H-TPP as
      a substrate and mitochondria isolated from mouse liver and human-derived liver
      HepG2 cells. Results showed (3)H-TPP uptake by mouse liver mitochondria to be pH
      independent, saturable (Km = 6.79+/-0.53 uM), and specific for TPP. MTPPT protein
      was expressed in mouse liver and HepG2 cells, and confocal images showed a human
      (h)MTPPT-GFP construct to be targeted to mitochondria of HepG2 cells. A serial
      truncation analysis revealed that all three modules of hMTPPT protein cooperated
      (although at different levels of efficiency) in mitochondrial targeting rather
      than acting autonomously as independent targeting module. Finally, the hMTPPT
      clinical mutants (G125S and G177A) showed proper mitochondrial targeting but
      displayed significant inhibition in (3)H-TPP uptake and a decrease in level of
      expression of the MTPPT protein. These findings advance our knowledge of the
      physiology and cell biology of the mitochondrial TPP uptake process. The results
      also show that clinical mutations in the hMTPPT system impair its functionality
      via affecting its level of expression with no effect on its targeting to
      mitochondria.

PMID- 24023688
TI  - Characterization of treatment-naive HIV/HBV co-infected patients attending ART
      clinic of a tertiary healthcare centre in eastern India.
AB  - OBJECTIVE: The study was designed to assess the hepatitis B virus (HBV) and
      hepatitis C virus (HCV) co-infection scenario among the human immunodeficiency
      virus (HIV) infected patients attending a tertiary healthcare unit in eastern
      India. Additionally, clinical and virological characterization of these viruses,
      prior to antiretroviral therapy (ART) initiation was also done for better
      understanding of the disease profile. METHODS: Pool of ART-naive HIV/HBV co
      infected and HIV mono-infected patients, participating in two different studies,
      were included in this study. HBV DNA was detected by nested-PCR amplification
      followed by HBV genotype determination and HBV reverse transcriptase (RT) region
      amplification and direct sequencing for detecting drug resistance. RESULTS: The
      prevalence of HBsAg (11.3%) was higher compared to anti-HCV (1.9%) among the HIV
      infected ART-naive patients. Moreover, majority of the HBeAg positive HIV/HBV co
      infected patients (87.7%) had HBV DNA >=20,000 IU/ml with median HBV DNA
      significantly higher than that of HBeAg negative subjects (5.7 log10 IU/ml vs.
      4.2 log10 IU/ml; p<0.0001). Multivariate analysis also showed that HBeAg-positive
      status was independently associated with higher HBV DNA level (p = <0.001).
      Notably, 60.9% of the HBeAg negative co-infected subjects had HBV DNA >=2,000
      IU/ml of which 37.0% had HBV DNA >=20,000 IU/ml. Genotype HBV/D (68.2%) was the
      predominant genotype followed by HBV/A (24.3%) and HBV/C (7.5%). Anti-HBV drug
      resistant mutations were detected in two (3.8%) of the ART-naive patients.
      CONCLUSION: The prevalence of HIV/HBV co-infection was relatively higher in our
      study subjects. HBeAg testing might provide clue for early treatment initiation.
      Furthermore, HBeAg negative patients are also associated with high HBV DNA levels
      and therefore require appropriate medical attention. Pre-treatment screening for
      anti-HBV drug resistant mutations is not necessary before ART initiation.

PMID- 24023689
TI  - The human cathelicidin LL-37 has antiviral activity against respiratory syncytial
      virus.
AB  - Respiratory syncytial virus is a leading cause of lower respiratory tract illness
      among infants, the elderly and immunocompromised individuals. Currently, there is
      no effective vaccine or disease modifying treatment available and novel
      interventions are urgently required. Cathelicidins are cationic host defence
      peptides expressed in the inflamed lung, with key roles in innate host defence
      against infection. We demonstrate that the human cathelicidin LL-37 has effective
      antiviral activity against RSV in vitro, retained by a truncated central peptide
      fragment. LL-37 prevented virus-induced cell death in epithelial cultures,
      significantly inhibited the production of new infectious particles and diminished
      the spread of infection, with antiviral effects directed both against the viral
      particles and the epithelial cells. LL-37 may represent an important targetable
      component of innate host defence against RSV infection. Prophylactic modulation
      of LL-37 expression and/or use of synthetic analogues post-infection may
      represent future novel strategies against RSV infection. 

PMID- 24023690
TI  - Reactivation in working memory: an attractor network model of free recall.
AB  - The dynamic nature of human working memory, the general-purpose system for
      processing continuous input, while keeping no longer externally available
      information active in the background, is well captured in immediate free recall
      of supraspan word-lists. Free recall tasks produce several benchmark memory
      phenomena, like the U-shaped serial position curve, reflecting enhanced memory
      for early and late list items. To account for empirical data, including primacy
      and recency as well as contiguity effects, we propose here a neurobiologically
      based neural network model that unifies short- and long-term forms of memory and
      challenges both the standard view of working memory as persistent activity and
      dual-store accounts of free recall. Rapidly expressed and volatile synaptic
      plasticity, modulated intrinsic excitability, and spike-frequency adaptation are
      suggested as key cellular mechanisms underlying working memory encoding,
      reactivation and recall. Recent findings on the synaptic and molecular mechanisms
      behind early LTP and on spiking activity during delayed-match-to-sample tasks
      support this view. 

PMID- 24023691
TI  - Inducible knockdown of Plasmodium gene expression using the glmS ribozyme.
AB  - Conventional reverse genetic approaches for study of Plasmodium malaria parasite
      gene function are limited, or not applicable. Hence, new inducible systems are
      needed. Here we describe a method to control P. falciparum gene expression in
      which target genes bearing a glmS ribozyme in the 3' untranslated region are
      efficiently knocked down in transgenic P. falciparum parasites in response to
      glucosamine inducer. Using reporter genes, we show that the glmS ribozyme cleaves
      reporter mRNA in vivo leading to reduction in mRNA expression following
      glucosamine treatment. Glucosamine-induced ribozyme activation led to efficient
      reduction of reporter protein, which could be rapidly reversed by removing the
      inducer. The glmS ribozyme was validated as a reverse-genetic tool by integration
      into the essential gene and antifolate drug target dihydrofolate reductase
      thymidylate synthase (PfDHFR-TS). Glucosamine treatment of transgenic parasites
      led to rapid and efficient knockdown of PfDHFR-TS mRNA and protein. PfDHFR-TS
      knockdown led to a growth/arrest mutant phenotype and hypersensitivity to
      pyrimethamine. The glmS ribozyme may thus be a tool for study of essential genes
      in P. falciparum and other parasite species amenable to transfection. 

PMID- 24023692
TI  - Duration of chemotherapy for small cell lung cancer: a meta-analysis.
AB  - BACKGROUND: Maintenance chemotherapy is widely provided to patients with small
      cell lung cancer (SCLC). However, the benefits of maintenance chemotherapy
      compared with observation are a subject of debate. METHODOLOGY AND PRINCIPAL
      FINDINGS: To identify relevant literature, we systematically searched the
      Medline, Embase, and Cochrane Central Register of Controlled Trials databases.
      Eligible trials included patients with SCLC who either received maintenance
      chemotherapy (administered according to a continuous or switch strategy) or
      underwent observation. The primary outcome was 1-year mortality, and secondary
      outcomes were 2-year mortality, overall survival (OS), and progression-free
      survival (PFS). Of the 665 studies found in our search, we identified 14 relevant
      trials, which together reported data on 1806 patients with SCLC. When compared
      with observation, maintenance chemotherapy had no effect on 1-year mortality
      (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.66-1.19; P = 0.414), 2
      year mortality (OR: 0.82; 95% CI: 0.57-1.19; P = 0.302), OS (hazard ratio [HR]:
      0.87; 95% CI: 0.71-1.06; P = 0.172), or PFS (HR: 0.87; 95% CI: 0.62-1.22; P =
      0.432). However, subgroup analyses indicated that maintenance chemotherapy was
      associated with significantly longer PFS than observation in patients with
      extensive SCLC (HR, 0.72; 95% CI: 0.58-0.89; P = 0.003). Additionally, patients
      who were managed using the continuous strategy of maintenance chemotherapy
      appeared to be at a disadvantage in terms of PFS compared with patients who only
      underwent observation (HR, 1.27; 95% CI: 1.04-1.54; P = 0.018).
      CONCLUSIONS/SIGNIFICANCE: Maintenance chemotherapy failed to improve survival
      outcomes in patients with SCLC. However, a significant advantage in terms of PFS
      was observed for maintenance chemotherapy in patients with extensive disease.
      Additionally, our results suggest that the continuous strategy is inferior to
      observation; its clinical value needs to be investigated in additional trials.

PMID- 24023693
TI  - Genetic and cytological analysis of a novel type of low temperature-dependent
      intrasubspecific hybrid weakness in rice.
AB  - Hybrid weakness (HW) is an important postzygotic isolation which occurs in both
      intra- and inter-specific crosses. In this study, we described a novel low
      temperature-dependent intrasubspecific hybrid weakness in the F1 plants derived
      from the cross between two indica rice varieties Taifeng A and V1134. HW plants
      showed growth retardation, reduced panicle number and pale green leaves with
      chlorotic spots. Cytological assay showed that there were reduced cell numbers,
      larger intercellular spaces, thicker cell walls, and abnormal development of
      chloroplast and mitochondria in the mature leaves from HW F1 plants in comparison
      with that from both of the parental lines. Genetic analysis revealed that HW was
      controlled by two complementary dominant genes Hw3 from V1134 and Hw4 from
      Taifeng A. Hw3 was mapped in a 136 kb interval between the markers Indel1118 and
      Indel1117 on chromosome 11, and Hw4 was mapped in the region of about 15 cM
      between RM182 and RM505 on chromosome 7, respectively. RT-PCR analysis revealed
      that only LOC_Os11g44310, encoding a putative calmodulin-binding protein
      (OsCaMBP), differentially expressed among Taifeng A, V1134 and their HW F1. No
      recombinant was detected using the markers designed based on the sequence of
      LOC_Os11g44310 in the BC1F2 (Taifeng A//Taifeng A/V1134) population. Hence,
      LOC_Os11g44310 was probably the candidate gene of Hw3. Gene amplification
      suggested that LOC_Os11g44310 was present in V1134 and absent in Taifeng A. BLAST
      search revealed that LOC_Os11g44310 had one copy in the japonica genomic sequence
      of Nipponbare, and no homologous sequence in the indica reference sequence of
      9311. Our results indicate that Hw3 is a novel gene for inducing hybrid weakness
      in rice. 

PMID- 24023694
TI  - Use of autologous human mesenchymal stromal cell/fibrin clot constructs in upper
      limb non-unions: long-term assessment.
AB  - BACKGROUND: Tissue engineering appears to be an attractive alternative to the
      traditional approach in the treatment of fracture non-unions. Mesenchymal stromal
      cells (MSCs) are considered an appealing cell source for clinical intervention.
      However, ex vivo cell expansion and differentiation towards the osteogenic
      lineage, together with the design of a suitable scaffold have yet to be
      optimized. Major concerns exist about the safety of MSC-based therapies,
      including possible abnormal overgrowth and potential cancer evolution. AIMS: We
      examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs,
      embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis
      of the upper limb. Our research work relied on three main issues: use of an
      entirely autologous context (cells, serum for ex vivo cell culture, scaffold
      components), reduced ex vivo cell expansion, and short-term MSC osteoinduction
      before implantation. METHODS AND FINDINGS: Bone marrow MSCs isolated from 8
      patients were expanded ex vivo until passage 1 and short-term osteo
      differentiated in autologous-based culture conditions. Tissue-engineered
      constructs designed to embed MSCs in autologous fibrin clots were locally
      implanted with bone grafts, calibrating their number on the extension of bone
      damage. Radiographic healing was evaluated with short- and long-term follow-ups
      (range averages: 6.7 and 76.0 months, respectively). All patients recovered limb
      function, with no evidence of tissue overgrowth or tumor formation. CONCLUSIONS:
      Our study indicates that highly autologous treatment can be effective and safe in
      the long-term healing of bone non-unions. This tissue engineering approach
      resulted in successful clinical and functional outcomes for all patients.

PMID- 24023695
TI  - Molecular chaperone mediated late-stage neuroprotection in the SOD1(G93A) mouse
      model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder
      characterized by the selective loss of motor neurons in the spinal cord, brain
      stem, and motor cortex. Mutations in superoxide dismutase (SOD1) are associated
      with familial ALS and lead to SOD1 protein misfolding and aggregation. Here we
      show that the molecular chaperone, HSJ1 (DNAJB2), mutations in which cause distal
      hereditary motor neuropathy, can reduce mutant SOD1 aggregation and improve motor
      neuron survival in mutant SOD1 models of ALS. Overexpression of human HSJ1a
      (hHSJ1a) in vivo in motor neurons of SOD1(G93A) transgenic mice ameliorated
      disease. In particular, there was a significant improvement in muscle force,
      increased motor unit number and enhanced motor neuron survival. hHSJ1a was
      present in a complex with SOD1(G93A) and led to reduced SOD1 aggregation at late
      stages of disease progression. We also observed altered ubiquitin
      immunoreactivity in the double transgenic animals, suggesting that ubiquitin
      modification might be important for the observed improvements. In a cell model of
      SOD1(G93A) aggregation, HSJ1a preferentially bound to mutant SOD1, enhanced SOD1
      ubiquitylation and reduced SOD1 aggregation in a J-domain and ubiquitin
      interaction motif (UIM) dependent manner. Collectively, the data suggest that
      HSJ1a acts on mutant SOD1 through a combination of chaperone, co-chaperone and
      pro-ubiquitylation activity. These results show that targeting SOD1 protein
      misfolding and aggregation in vivo can be neuroprotective and suggest that
      manipulation of DnaJ molecular chaperones might be useful in the treatment of
      ALS. 

PMID- 24023696
TI  - Cobas ampliprep/cobas TaqMan HIV-1 v2.0 assay: consequences at the cohort level.
AB  - BACKGROUND: High-sensitive real-time PCR assays are routinely used to monitor HIV
      1 infected subjects. Inter-assay discrepancies have been described at the low
      viral load (VL) end, where clinical decisions regarding possible virological
      rebound are based. METHODS: A retrospective study was performed to analyze
      frequencies of viral blips after transition to the COBAS Ampliprep/COBAS TaqMan
      v2.0 HIV-1 assay (Taqman v2.0) in patients with prior undetectable VLs as
      measured with the Roche Cobas Ampliprep Amplicor HIV-1 Monitor Test, v1.5
      (Amplicor) and was evaluated in comparison to a group of patients monitored with
      the Abbott Real-time HIV-1 assay (Abbott RT) during the same period of time.
      RESULTS: 85 of 373 patients with VLs below the limit of quantification with
      Amplicor had VLs >50 copies/mL after transition to the TaqMan v2.0 assay. Among
      these 74.1% had VLs ranging from 50-499 copies/mL, 22.9% had VLs >500 copies/mL.
      From 22 patients with initial Taqman v2.0 based VLs exceeding 500 copies/mL, 6
      patients had VLs <20 copies/mL after novel VL measurement on a next visit. In our
      control group with VL quantification using the Abbott RT assay, only 1 patient
      became detectable and showed a VL of <40 copies/mL after new measurement.
      CONCLUSIONS: Transition to the Taqman v2.0 assay was accompanied by an increase
      of quantifiable HIV-1 VLs in patients with long term viral suppression under
      antiretroviral therapy that might be attributed to technical shortcomings of the
      Taqman v2.0 assay. A high test variability at the low VL end but also beyond was
      observed, making meaningful clinical interpretation of viral blips derived from
      different assays difficult.

PMID- 24023697
TI  - The dopamine D3 receptor knockout mouse mimics aging-related changes in autonomic
      function and cardiac fibrosis.
AB  - Blood pressure increases with age, and dysfunction of the dopamine D3 receptor
      has been implicated in the pathogenesis of hypertension. To evaluate the role of
      the D3 receptor in aging-related hypertension, we assessed cardiac structure and
      function in differently aged (2 mo, 1 yr, 2 yr) wild type (WT) and young (2 mo)
      D3 receptor knockout mice (D3KO). In WT, systolic and diastolic blood pressures
      and rate-pressure product (RPP) significantly increased with age, while heart
      rate significantly decreased. Blood pressure values, heart rate and RPP of young
      D3KO were significantly elevated over age-matched WT, but similar to those of the
      2 yr old WT. Echocardiography revealed that the functional measurements of
      ejection fraction and fractional shortening decreased significantly with age in
      WT and that they were significantly smaller in D3KO compared to young WT. Despite
      this functional change however, cardiac morphology remained similar between the
      age-matched WT and D3KO. Additional morphometric analyses confirmed an aging
      related increase in left ventricle (LV) and myocyte cross-sectional areas in WT,
      but found no difference between age-matched young WT and D3KO. In contrast,
      interstitial fibrosis, which increased with age in WT, was significantly elevated
      in the D3KO over age-matched WT, and similar to 2 yr old WT. Western analyses of
      myocardial homogenates revealed significantly increased levels of pro- and mature
      collagen type I in young D3KO. Column zymography revealed that activities of
      myocardial MMP-2 and MMP-9 increased with age in WTs, but in D3KO, only MMP-9
      activity was significantly increased over age-matched WTs. Our data provide
      evidence that the dopamine D3 receptor has a critical role in the emergence of
      aging-related cardiac fibrosis, remodeling, and dysfunction. 

PMID- 24023698
TI  - Short-term overfeeding increases circulating adiponectin independent of obesity
      status.
AB  - BACKGROUND: Adiponectin is an adipose tissue derived hormone which strengthens
      insulin sensitivity. However, there is little data available regarding the
      influence of a positive energy challenge (PEC) on circulating adiponectin and the
      role of obesity status on this response. OBJECTIVE: The purpose of this study was
      to investigate how circulating adiponectin will respond to a short-term PEC and
      whether or not this response will differ among normal-weight(NW), overweight(OW)
      and obese(OB). DESIGN: We examined adiponectin among 64 young men (19-29 yr)
      before and after a 7-day overfeeding (70% above normal energy requirements). The
      relationship between adiponectin and obesity related phenotypes including;
      weight, percent body fat (%BF), percent trunk fat (%TF), percent android fat
      (%AF), body mass index (BMI), total cholesterol, HDLc, LDLc, glucose, insulin,
      homeostatic model assessment insulin resistance (HOMA-IR) and beta-cell function
      (HOMA-beta) were analyzed before and after overfeeding. RESULTS: Analysis of
      variance (ANOVA) and partial correlations were used to compute the effect of
      overfeeding on adiponectin and its association with adiposity measurements,
      respectively. Circulating Adiponectin levels significantly increased after the 7
      day overfeeding in all three adiposity groups. Moreover, adiponectin at baseline
      was not significantly different among NW, OW and OB subjects defined by either
      %BF or BMI. Baseline adiponectin was negatively correlated with weight and BMI
      for the entire cohort and %TF, glucose, insulin and HOMA-IR in OB. However, after
      controlling for insulin resistance the correlation of adiponectin with weight,
      BMI and %TF were nullified. CONCLUSION: Our study provides evidence that the
      protective response of adiponectin is preserved during a PEC regardless of
      adiposity. Baseline adiponectin level is not directly associated with obesity
      status and weight gain in response to short-term overfeeding. However, the
      significant increase of adiponectin in response to overfeeding indicates the
      physiological potential for adiponectin to attenuate insulin resistance during
      the development of obesity.

PMID- 24023699
TI  - The impact of low-dose insulin on peripheral nerve insulin receptor signaling in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: The precise mechanisms of the neuroprotective effects of insulin in
      streptozotocin (STZ)-induced diabetic animals remain unknown, but altered
      peripheral nerve insulin receptor signaling due to insulin deficiency might be
      one cause. METHODOLOGY AND PRINCIPAL FINDINGS: Diabetes was induced in 10-week
      old, male Wistar rats by injecting them with STZ (45 mg/kg). They were assigned
      to one group that received half of an insulin implant (~1 U/day; I-group, n = 11)
      or another that remained untreated (U-group, n = 10) for 6 weeks. The controls
      were age- and sex-matched, non-diabetic Wistar rats (C-group, n = 12). Low-dose
      insulin did not change haemoglobin A1c, which increased by 136% in the U-group
      compared with the C-group. Thermal hypoalgesia and mechanical hyperalgesia
      developed in the U-group, but not in the I-group. Sensory and motor nerve
      conduction velocities decreased in the U-group, whereas sensory nerve conduction
      velocity increased by 7% (p = 0.0351) in the I-group compared with the U-group.
      Western blots showed unaltered total insulin receptor (IR), but a 31% decrease
      and 3.1- and 4.0-fold increases in phosphorylated IR, p44, and p42 MAPK protein
      levels, respectively, in sciatic nerves from the U-group compared with the C
      group. Phosphorylated p44/42 MAPK protein decreased to control levels in the I
      group (p<0.0001). CONCLUSIONS AND SIGNIFICANCE: Low-dose insulin deactivated
      p44/42 MAPK and ameliorated peripheral sensory nerve dysfunction in rats with STZ
      induced diabetes. These findings support the notion that insulin deficiency per
      se introduces impaired insulin receptor signaling in type 1 diabetic neuropathy.

PMID- 24023700
TI  - HPV prevalence among women from Appalachia: results from the CARE project.
AB  - BACKGROUND: Cervical cancer incidence and mortality rates are high among women
      from Appalachia, yet data do not exist on human papillomavirus (HPV) prevalence
      among these women. We examined the prevalence of genital HPV among Appalachian
      women and identified correlates of HPV detection. METHODS: We report data from a
      case-control study conducted between January 2006 and December 2008 as part of
      the Community Awareness, Resources, and Education (CARE) Project. We examined HPV
      prevalence among 1116 women (278 women with abnormal Pap tests at study entry
      [cases], 838 women with normal Pap tests [controls]) from Appalachian Ohio.
      Analyses used multivariable logistic regression to identify correlates of HPV
      detection. RESULTS: The prevalence of HPV was 43.1% for any HPV type, 33.5% for
      high-risk HPV types, 23.4% for low-risk HPV types, and 12.5% for vaccine
      preventable HPV types. Detection of any HPV type was more common among women who
      were ages 18-26 (OR = 2.09, 95% CI: 1.26-3.50), current smokers (OR = 1.86, 95%
      CI: 1.26-2.73), had at least five male sexual partners during their lifetime (OR
      = 2.28, 95% CI: 1.56-3.33), or had multiple male sexual partners during the last
      year (OR = 1.98, 95% CI: 1.25-3.14). Similar correlates were identified for
      detection of a high-risk HPV type. CONCLUSIONS: HPV was prevalent among
      Appalachian women, with many women having a high-risk HPV type detected. Results
      may help explain the high cervical cancer rates observed among Appalachian women
      and can help inform future cervical cancer prevention efforts in this geographic
      region.

PMID- 24023701
TI  - Involvement of the serine protease inhibitor, SERPINE2, and the urokinase
      plasminogen activator in cumulus expansion and oocyte maturation.
AB  - The serpin peptidase inhibitor, clade E, member 2 (SERPINE2) inhibits urokinase
      type plasminogen activator (PLAU) and tissue-type plasminogen activator. Higher
      SERPINE2 expression levels were detected in cumulus cells of human immature
      oocytes than in those of mature oocytes. The objective of this study was to
      evaluate whether high SERPINE2 levels in cumulus cells are associated with oocyte
      immaturity. Using the mouse cumulus-oocyte complex as an experimental model, the
      effects of elimination and overexpression of SERPINE2 in cumulus cells on cumulus
      expansion and oocyte maturation were assayed by in vitro maturation. Serpine2 and
      PLAU transcripts were the most highly expressed serpins and plasminogen
      activators, respectively. Their expression was coordinately regulated in cumulus
      cells during gonadotropin-induced oocyte maturation. Silencing of Serpine2
      expression using small interfering RNAs or blockage of SERPINE2 protein using a
      specific antibody had no effect on oocyte maturation. However, overexpression of
      Serpine2 or exogenous supplementation with high levels of SERPINE2 impaired
      cumulus expansion and oocyte maturation, probably by decreasing hyaluronan
      synthase 2 (Has2) and versican (Vcan) mRNA expression. Amiloride, a specific PLAU
      inhibitor, also suppressed these processes. PLAU supplementation of the oocyte in
      vitro maturation medium caused earlier and more extensive expansion of cumulus
      cells and oocyte maturation that may be mediated by increased Has2 mRNA
      expression. However, these effects were neutralized by coincubation with SERPINE2
      or amiloride and PLAU. In conclusion, SERPINE2 and PLAU are involved in cumulus
      expansion and oocyte maturation. High SERPINE2 levels impair these processes,
      probably by decreasing cumulus matrix gene expression as well as reducing cumulus
      hyaluronan contents and inhibiting PLAU activity. These findings may explain why
      cumulus cells surrounding immature human oocytes express high SERPINE2 levels. 

PMID- 24023702
TI  - A divergent Artiodactyl MYADM-like repeat is associated with erythrocyte traits
      and weight of lamb weaned in domestic sheep.
AB  - A genome-wide association study (GWAS) was performed to investigate seven red
      blood cell (RBC) phenotypes in over 500 domestic sheep (Ovis aries) from three
      breeds (Columbia, Polypay, and Rambouillet). A single nucleotide polymorphism
      (SNP) showed genome-wide significant association with increased mean corpuscular
      hemoglobin concentration (MCHC, P = 6.2*10(-14)) and genome-wide suggestive
      association with decreased mean corpuscular volume (MCV, P = 2.5*10(-6)). The
      ovine HapMap project found the same genomic region and the same peak SNP has been
      under extreme historical selective pressure, demonstrating the importance of this
      region for survival, reproduction, and/or artificially selected traits. We
      observed a large (>50 kb) variant haplotype sequence containing a full-length
      divergent artiodactyl MYADM-like repeat in strong linkage disequilibrium with the
      associated SNP. MYADM gene family members play roles in membrane organization and
      formation in myeloid cells. However, to our knowledge, no member of the MYADM
      gene family has been identified in development of morphologically variant RBCs.
      The specific RBC differences may be indicative of alterations in morphology.
      Additionally, erythrocytes with altered morphological structure often exhibit
      increased structural fragility, leading to increased RBC turnover and energy
      expenditure. The divergent artiodactyl MYADM-like repeat was also associated with
      increased ewe lifetime kilograms of lamb weaned (P = 2*10(-4)). This suggests
      selection for normal RBCs might increase lamb weights, although further
      validation is required before implementation in marker-assisted selection. These
      results provide clues to explain the strong selection on the artiodactyl MYADM
      like repeat locus in sheep, and suggest MYADM family members may be important for
      RBC morphology in other mammals. 

PMID- 24023704
TI  - Potential stream density in Mid-Atlantic US watersheds.
AB  - Stream network density exerts a strong influence on ecohydrologic processes in
      watersheds, yet existing stream maps fail to capture most headwater streams and
      therefore underestimate stream density. Furthermore, discrepancies between mapped
      and actual stream length vary between watersheds, confounding efforts to
      understand the impacts of land use on stream ecosystems. Here we report on
      research that predicts stream presence from coupled field observations of
      headwater stream channels and terrain variables that were calculated both locally
      and as an average across the watershed upstream of any location on the landscape.
      Our approach used maximum entropy modeling (MaxEnt), a robust method commonly
      implemented to model species distributions that requires information only on the
      presence of the entity of interest. In validation, the method correctly predicts
      the presence of 86% of all 10-m stream segments and errors are low (<1%) for
      catchments larger than 10 ha. We apply this model to the entire Potomac River
      watershed (37,800 km(2)) and several adjacent watersheds to map stream density
      and compare our results with the National Hydrography Dataset (NHD). We find that
      NHD underestimates stream density by up to 250%, with errors being greatest in
      the densely urbanized cities of Washington, DC and Baltimore, MD and in regions
      where the NHD has never been updated from its original, coarse-grain mapping.
      This work is the most ambitious attempt yet to map stream networks over a large
      region and will have lasting implications for modeling and conservation efforts. 

PMID- 24023703
TI  - Complete sequence and comparative analysis of the chloroplast genome of coconut
      palm (Cocos nucifera).
AB  - Coconut, a member of the palm family (Arecaceae), is one of the most economically
      important trees used by mankind. Despite its diverse morphology, coconut is
      recognized taxonomically as only a single species (Cocos nucifera L.). There are
      two major coconut varieties, tall and dwarf, the latter of which displays traits
      resulting from selection by humans. We report here the complete chloroplast (cp)
      genome of a dwarf coconut plant, and describe the gene content and organization,
      inverted repeat fluctuations, repeated sequence structure, and occurrence of RNA
      editing. Phylogenetic relationships of monocots were inferred based on 47
      chloroplast protein-coding genes. Potential nodes for events of gene duplication
      and pseudogenization related to inverted repeat fluctuation were mapped onto the
      tree using parsimony criteria. We compare our findings with those from other palm
      species for which complete cp genome sequences are available. 

PMID- 24023705
TI  - Induced fungal resistance to insect grazing: reciprocal fitness consequences and
      fungal gene expression in the Drosophila-Aspergillus model system.
AB  - BACKGROUND: Fungi are key dietary resources for many animals. Fungi, in
      consequence, have evolved sophisticated physical and chemical defences for
      repelling and impairing fungivores. Expression of such defences may entail costs,
      requiring diversion of energy and nutrients away from fungal growth and
      reproduction. Inducible resistance that is mounted after attack by fungivores may
      allow fungi to circumvent the potential costs of defence when not needed.
      However, no information exists on whether fungi display inducible resistance. We
      combined organism and fungal gene expression approaches to investigate whether
      fungivory induces resistance in fungi. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      show that grazing by larval fruit flies, Drosophila melanogaster, induces
      resistance in the filamentous mould, Aspergillus nidulans, to subsequent feeding
      by larvae of the same insect. Larval grazing triggered the expression of various
      putative fungal resistance genes, including the secondary metabolite master
      regulator gene laeA. Compared to the severe pathological effects of wild type A.
      nidulans, which led to 100% insect mortality, larval feeding on a laeA loss-of
      function mutant resulted in normal insect development. Whereas the wild type
      fungus recovered from larval grazing, larvae eradicated the chemically deficient
      mutant. In contrast, mutualistic dietary yeast, Saccharomyces cerevisiae, reached
      higher population densities when exposed to Drosophila larval feeding.
      CONCLUSIONS/SIGNIFICANCE: Our study presents novel evidence that insect grazing
      is capable of inducing resistance to further grazing in a filamentous fungus.
      This phenotypic shift in resistance to fungivory is accompanied by changes in the
      expression of genes involved in signal transduction, epigenetic regulation and
      secondary metabolite biosynthesis pathways. Depending on reciprocal insect-fungus
      fitness consequences, fungi may be selected for inducible resistance to maintain
      high fitness in fungivore-rich habitats. Induced fungal defence responses thus
      need to be included if we wish to have a complete conception of animal-fungus co
      evolution, fungal gene regulation, and multitrophic interactions.

PMID- 24023707
TI  - Post-zygotic and inter-individual structural genetic variation in a presumptive
      enhancer element of the locus between the IL10Rbeta and IFNAR1 genes.
AB  - Although historically considered as junk-DNA, tandemly repeated sequence motifs
      can affect human phenotype. For example, variable number tandem repeats (VNTR)
      with embedded enhancers have been shown to regulate gene transcription. The post
      zygotic variation is the presence of genetically distinct populations of cells in
      an individual derived from a single zygote, and this is an understudied aspect of
      genome biology. We report somatically variable VNTR with sequence properties of
      an enhancer, located upstream of IFNAR1. Initially, SNP genotyping of 63
      monozygotic twin pairs and multiple tissues from 21 breast cancer patients
      suggested a frequent post-zygotic mosaicism. The VNTR displayed a repeated 32 bp
      core motif in the center of the repeat, which was flanked by similar variable
      motifs. A total of 14 alleles were characterized based on combinations of
      segments, which showed post-zygotic and inter-individual variation, with up to 6
      alleles in a single subject. Somatic variation occurred in ~24% of cases. In this
      hypervariable region, we found a clustering of transcription factor binding sites
      with strongest sequence similarity to mouse Foxg1 transcription factor binding
      motif. This study describes a VNTR with sequence properties of an enhancer that
      displays post-zygotic and inter-individual genetic variation. This element is
      within a locus containing four related cytokine receptors: IFNAR2, IL10Rbeta,
      IFNAR1 and IFNGR2, and we hypothesize that it might function in transcriptional
      regulation of several genes in this cluster. Our findings add another level of
      complexity to the variation among VNTR-based enhancers. Further work may unveil
      the normal function of this VNTR in transcriptional control and its possible
      involvement in diseases connected with these receptors, such as autoimmune
      conditions and cancer. 

PMID- 24023708
TI  - The circadian variation in Anti-Mullerian hormone in patients with polycystic
      ovary syndrome differs significantly from normally ovulating women.
AB  - OBJECTIVE: [corrected] To improve the biologic understanding of the Polycystic
      Ovarian Syndrome (PCOS) condition by examining the circadian variation and
      relationship between Anti Mullerian Hormone (AMH), gonadotropins and ovarian
      steroids in PCOS patients compared to normally ovulating and menstruating women.
      By comparing the pattern of co-variation between AMH and Luteinizing Hormone, two
      compounds closely linked to hyperandrogenism and anovulation in PCOS, the
      involvement of the Hypothalamic-Pituitary-Ovarian axis in PCOS pathology could be
      elucidated. PATIENTS: Eight normal-weighted young, anovulatory PCOS-women as
      study group and ten normal menstruating and ovulating women as controls.
      INTERVENTIONS: Observational prospective study of the circadian variation in AMH,
      gonadotropins, sex steroids and androgens in a study and a control group. A
      circadian profile was performed in each study and control subject during a 24-h
      period by blood sampling every second hour, starting at 8:00 a.m. and continuing
      until 8:00 a.m. the following day. RESULTS: Significant differences in hormonal
      levels were found between the groups, with higher concentrations of AMH, LH and
      androgens in the PCOS group and lower amounts of FSH and progesterone. A distinct
      difference in the circadian variation pattern of AMH and LH between PCOS patients
      and normal controls was seen, with PCOS patients presenting a uniform pattern in
      serum levels of AMH and LH throughout the study period, without significant nadir
      late-night values as was seen in the control group. In PCOS women, a significant
      positive association between LH/ FSH and testosterone was found opposite to
      controls. MAIN OUTCOME MEASURES: Circadian variation in Anti-Mullerian Hormone,
      gonadotropins and ovarian steroids and the covariation between them. CONCLUSION:
      A significant difference in the circadian secretion of LH and AMH in PCOS women
      compared to normally ovulating women indicate an increased GnRH pulse, creating
      high and constant LH serum concentrations. A significant co-variation between LH
      and AMH may suggest LH as a factor involved in the control of AMH secretion.

PMID- 24023709
TI  - Involvement of the neutral amino acid transporter SLC6A15 and leucine in obesity
      related phenotypes.
AB  - Brain pathways, including those in hypothalamus and nucleus of the solitary
      tract, influence food intake, nutrient preferences, metabolism and development of
      obesity in ways that often differ between males and females. Branched chain amino
      acids, including leucine, can suppress food intake, alter metabolism and change
      vulnerability to obesity. The SLC6A15 (v7-3) gene encodes a sodium-dependent
      transporter of leucine and other branched chain amino acids that is expressed by
      neurons in hypothalamus and nucleus of the solitary tract. We now report that
      SLC6A15 knockout attenuates leucine's abilities to reduce both: a) intake of
      normal chow and b) weight gain produced by access to a high fat diet in gender
      selective fashions. We identify SNPs in the human SLC6A15 that are associated
      with body mass index and insulin resistance in males. These observations in mice
      and humans support a novel, gender-selective role for brain amino acid
      compartmentalization mediated by SLC6A15 in diet and obesity-associated
      phenotypes. 

PMID- 24023710
TI  - Parkinson's disease is related to an increased risk of ischemic stroke-a
      population-based propensity score-matched follow-up study.
AB  - OBJECTIVE: The risk of stroke in patients with Parkinson's disease (PD) remains
      controversial. The purpose of this population-based propensity score-matched
      longitudinal follow-up study was to determine whether there is an increased risk
      of ischemic stroke after PD. METHODS: We used a logistic regression model that
      includes age, sex, pre-existing comorbidities and socioeconomic status as
      covariates to compute the propensity score. A total of 2204 patients with at
      least two ambulatory visits with the principal diagnosis of PD in 2001 was
      enrolled in the PD group. The non- PD group consisted of 2204, propensity score
      matched subjects without PD. The ischemic stroke-free survival rates of the two
      groups were estimated using the Kaplan-Meier method. Stratified Cox proportional
      hazard regression with patients matched on propensity score was used to estimate
      the effect of PD on the occurrence of ischemic stroke. RESULTS: During the three
      year follow-up period, 328 subjects in the PD group and 156 subjects in the non
      PD group developed ischemic stroke. The ischemic stroke-free survival rate of the
      PD group was significantly lower than that of the non-PD group (P<0.0001). The
      hazard ratio (HR) of stroke for the PD group was 2.37 (95% confidence interval
      [CI], 1.92 to 2.93, P<0.0001) compared to the non- PD group. CONCLUSIONS: This
      study shows a significantly increased risk of ischemic stroke in PD patients.
      Further studies are required to investigate the underlying mechanism.

PMID- 24023711
TI  - Complete genome analysis of a Haemophilus parasuis serovar 12 strain from China.
AB  - Haemophilus parasuis is the etiological agent of Glasser's disease in pigs and 15
      standard serovars were identified. The widespread disease causes great economic
      loss in the swine industry worldwide. Aiming to investigate the differences in
      genome composition and functions among various strains, a highly virulent strain
      ZJ0906 of H. parasuis serovar 12 from China was analyzed and compared with
      serovar 5 SH0165. Strain ZJ0906 genome is 2,324,740 base pairs with 40.06%
      genomic GC content. It contains 2,484 open reading frames (ORF) predicted by
      Glimmer 3.02, of which 2,352 (~94.7%) were annotated by NCBI nr blast, 1,745 by
      COG database and 1,829 by KEGG database. 109 potential virulence factors were
      annotated in strain ZJ0906 and 3 of which are potentially related to antibiotic
      resistance. Strain ZJ0906 genome is ~55 kilobases longer than SH0165 genome, with
      an extra 211 predicted ORFs. VFDB, ARDB, and PAIDB blast searches showed that
      ZJ0906 and SH0165 shared a nearly identical panel of potential virulence factors,
      drug resistant genes and four PAI-like regions which showed high homology to
      Enterococcus, Escherichia and Salmonella. Synteny analysis showed that gene
      rearrangements are frequent between the two strains, which may lead to variations
      in pathogenicity and cross-protection among serovars. KEGG pathway analyses
      showed strain ZJ0906 shared similar metabolic pathways to strain SH0165.
      Molecular identification of these genomic elements and potential virulence
      factors pave the way to the better understanding of mechanisms underlying
      metabolic capabilities and pathogenicity of H. parasuis and prospective vaccine
      targets besides the widely used method of inactivated bacteria. 

PMID- 24023712
TI  - Three-dimensional quantification of cellular traction forces and mechanosensing
      of thin substrata by fourier traction force microscopy.
AB  - We introduce a novel three-dimensional (3D) traction force microscopy (TFM)
      method motivated by the recent discovery that cells adhering on plane surfaces
      exert both in-plane and out-of-plane traction stresses. We measure the 3D
      deformation of the substratum on a thin layer near its surface, and input this
      information into an exact analytical solution of the elastic equilibrium
      equation. These operations are performed in the Fourier domain with high
      computational efficiency, allowing to obtain the 3D traction stresses from raw
      microscopy images virtually in real time. We also characterize the error of
      previous two-dimensional (2D) TFM methods that neglect the out-of-plane component
      of the traction stresses. This analysis reveals that, under certain combinations
      of experimental parameters (cell size, substratums' thickness and Poisson's
      ratio), the accuracy of 2D TFM methods is minimally affected by neglecting the
      out-of-plane component of the traction stresses. Finally, we consider the cell's
      mechanosensing of substratum thickness by 3D traction stresses, finding that,
      when cells adhere on thin substrata, their out-of-plane traction stresses can
      reach four times deeper into the substratum than their in-plane traction
      stresses. It is also found that the substratum stiffness sensed by applying out
      of-plane traction stresses may be up to 10 times larger than the stiffness sensed
      by applying in-plane traction stresses. 

PMID- 24023713
TI  - The relationship of sleep with temperature and metabolic rate in a hibernating
      primate.
AB  - STUDY OBJECTIVES: It has long been suspected that sleep is important for
      regulating body temperature and metabolic-rate. Hibernation, a state of acute
      hypothermia and reduced metabolic-rate, offers a promising system for
      investigating those relationships. Prior studies in hibernating ground squirrels
      report that, although sleep occurs during hibernation, it manifests only as non
      REM sleep, and only at relatively high temperatures. In our study, we report data
      on sleep during hibernation in a lemuriform primate, Cheirogaleus medius. As the
      only primate known to experience prolonged periods of hibernation and as an
      inhabitant of more temperate climates than ground squirrels, this animal serves
      as an alternative model for exploring sleep temperature/metabolism relationships
      that may be uniquely relevant to understanding human physiology. MEASUREMENTS AND
      RESULTS: We find that during hibernation, non-REM sleep is absent in
      Cheirogaleus. Rather, periods of REM sleep occur during periods of relatively
      high ambient temperature, a pattern opposite of that observed in ground
      squirrels. Like ground squirrels, however, EEG is marked by ultra-low voltage
      activity at relatively low metabolic-rates. CONCLUSIONS: These findings confirm a
      sleep-temperature/metabolism link, though they also suggest that the relationship
      of sleep stage with temperature/metabolism is flexible and may differ across
      species or mammalian orders. The absence of non-REM sleep suggests that during
      hibernation in Cheirogaleus, like in the ground squirrel, the otherwise universal
      non-REM sleep homeostatic response is greatly curtailed or absent. Lastly, ultra
      low voltage EEG appears to be a cross-species marker for extremely low metabolic
      rate, and, as such, may be an attractive target for research on hibernation
      induction.

PMID- 24023714
TI  - Secondary structure of a conserved domain in the intron of influenza A NS1 mRNA.
AB  - Influenza A virus is a segmented single-stranded (-)RNA virus that causes
      substantial annual morbidity and mortality. The transcriptome of influenza A is
      predicted to have extensive RNA secondary structure. The smallest genome segment,
      segment 8, encodes two proteins, NS1 and NEP, via alternative splicing. A
      conserved RNA domain in the intron of segment 8 may be important for regulating
      production of NS1. Two different multi-branch loop structures have been proposed
      for this region. A combination of in vitro chemical mapping and isoenergetic
      microarray techniques demonstrate that the consensus sequence for this region
      folds into a hairpin conformation. These results provide an alternative folding
      for this region and a foundation for designing experiments to probe its
      functional role in the influenza life cycle. 

PMID- 24023715
TI  - DYRK2 negatively regulates cardiomyocyte growth by mediating repressor function
      of GSK-3beta on eIF2Bepsilon.
AB  - BACKGROUND: A prerequisite of hypertrophic response of the myocardium is an
      increase in protein synthesis. A central regulator of translation initiation is
      Eukaryotic initiation factor 2B (eIF2B). Here we assessed the hypothesis that
      regulation of protein synthesis via eIF2Bepsilon is essential to cardiac
      hypertrophic response in vivo. METHODS: Two transgenic mouse lines were generated
      with cardiac restricted overexpression of eIF2Bepsilon or its mutant eIF2Bepsilon
      eIFS(535)A, which cannot be inactivated by phosphorylation through GSK-3beta.
      RESULTS: (1) Under baseline conditions eIF2Bepsilon transgenic mice showed no
      difference in cardiac phenotype compared to wild type, whereas in the mutant
      eIF2Bepsilon-S(535)A an increase in LV/tibia length (7.5 +/- 0.4 mg/mm vs. 6.2 +/
      0.2 mg/mm, p<0.001) and cardiomyocyte cross sectional area (13004 +/- 570 vs.
      10843 +/- 347 RU, p<0.01) was observed. (2) Cardiac overexpression of
      eIF2Bepsilon did not change the response of the heart to pathologic stress
      induced by chronic isoproterenol treatment. (3) Cardiac overexpression of the
      eIF2Bepsilon transgene was followed by overexpression of DYRK2 which is known to
      prime the inhibitory action of GSK-3beta on eIF2Bepsilon, while DYRK1A and GSK
      3beta itself were not increased. (4) In C57BL/6 mice after 48 h of isoproterenol
      stimulation or aortic banding, eIF2Bepsilon was increased and DYRK2 was
      concomitantly decreased. (5) In line with these in vivo findings, siRNA knockdown
      of DYRK2 in cultured cardiomyocytes resulted in decreased levels of p(S535)-
      eIF2Bepsilon, (6) whereas adenoviral induced overexpression of DYRK2 was
      accompanied by clearly increased phosphorylation of eIF2Bepsilon, indicating a
      coordinated response pattern (7) Adenoviral induced overexpression of DYRK2 leads
      to significantly reduced cardiomyocyte size and diminishes hypertrophic response
      to adrenergic stimulation. CONCLUSIONS: The interaction of GSK-3beta and its
      priming kinase DYRK2 regulate the activity of eIF2Bepsilon in cardiac myocytes.
      DYRK2 is a novel negative regulator of cardiomyocyte growth. DYRK2 could serve as
      a therapeutic option to regulate myocardial growth.

PMID- 24023716
TI  - FoxP1 stimulates angiogenesis by repressing the inhibitory guidance protein
      semaphorin 5B in endothelial cells.
AB  - Forkhead box (Fox) transcription factors are important regulators of
      cardiovascular development and several Fox-proteins have recently been shown to
      modulate embryonic and post-natal angiogenesis. However, the role of the FoxP
      subfamily, which is highly expressed in cardiovascular tissue, has not been
      investigated so far. Here, we show that the transcription factor FoxP1 is the
      highest expressed FoxP-protein in endothelial cells and that it is upregulated at
      the site of neovascularization during hindlimb ischemia in mice. Silencing of
      FoxP1 results in a strong inhibition of proliferation, tube formation and
      migration of cultured endothelial cells. Accordingly, knockdown of FoxP1 in
      zebrafish was followed by a disruption of intersomitic vascular formation. Using
      gene expression profiling, we show that FoxP1 induces a specific change of the
      endothelial transcriptome and functions as a suppressor of semaphorin 5B, which
      has previously been described as a neuronal inhibitory factor. Our findings now
      demonstrate that semaphorin 5B also acts as a FoxP1- dependent suppressor of
      endothelial cell proliferation, migration and sprouting, mediating the effects of
      FoxP1. In summary, our data indicate that the transcription factor FoxP1 is
      essential for the angiogenic function of endothelial cells and functions as a
      suppressor of the inhibitory guidance cue semaphorin 5B, suggesting an important
      function of FoxP1 in the regulation of neovascularization. 

PMID- 24023717
TI  - Mapping of Mcs30, a new mammary carcinoma susceptibility quantitative trait locus
      (QTL30) on rat chromosome 12: identification of fry as a candidate Mcs gene.
AB  - Rat strains differ dramatically in their susceptibility to mammary
      carcinogenesis. On the assumption that susceptibility genes are conserved across
      mammalian species and hence inform human carcinogenesis, numerous investigators
      have used genetic linkage studies in rats to identify genes responsible for
      differential susceptibility to carcinogenesis. Using a genetic backcross between
      the resistant Copenhagen (Cop) and susceptible Fischer 344 (F344) strains, we
      mapped a novel mammary carcinoma susceptibility (Mcs30) locus to the centromeric
      region on chromosome 12 (LOD score of ~8.6 at the D12Rat59 marker). The Mcs30
      locus comprises approximately 12 Mbp on the long arm of rat RNO12 whose synteny
      is conserved on human chromosome 13q12 to 13q13. After analyzing numerous genes
      comprising this locus, we identified Fry, the rat ortholog of the furry gene of
      Drosophila melanogaster, as a candidate Mcs gene. We cloned and determined the
      complete nucleotide sequence of the 13 kbp Fry mRNA. Sequence analysis indicated
      that the Fry gene was highly conserved across evolution, with 90% similarity of
      the predicted amino acid sequence among eutherian mammals. Comparison of the Fry
      sequence in the Cop and F344 strains identified two non-synonymous single
      nucleotide polymorphisms (SNPs), one of which creates a putative, de novo
      phosphorylation site. Further analysis showed that the expression of the Fry gene
      is reduced in a majority of rat mammary tumors. Our results also suggested that
      FRY activity was reduced in human breast carcinoma cell lines as a result of
      reduced levels or mutation. This study is the first to identify the Fry gene as a
      candidate Mcs gene. Our data suggest that the SNPs within the Fry gene contribute
      to the genetic susceptibility of the F344 rat strain to mammary carcinogenesis.
      These results provide the foundation for analyzing the role of the human FRY gene
      in cancer susceptibility and progression. 

PMID- 24023718
TI  - The Universal Form of Treatment Options (UFTO) as an alternative to Do Not
      Attempt Cardiopulmonary Resuscitation (DNACPR) orders: a mixed methods evaluation
      of the effects on clinical practice and patient care.
AB  - AIMS: To determine whether the introduction of the Universal Form of Treatment
      Options (the UFTO), as an alternative approach to Do Not Attempt Cardiopulmonary
      Resuscitation (DNACPR) orders, reduces harms in patients in whom a decision not
      to attempt cardiopulmonary resuscitation (CPR) was made, and to understand the
      mechanism for any observed change. METHODS: A mixed-methods before-and-after
      study with contemporaneous case controls was conducted in an acute hospital. We
      examined DNACPR (103 patients with DNACPR orders in 530 admissions) and UFTO (118
      decisions not to attempt resuscitation in 560 admissions) practice. The Global
      Trigger Tool was used to quantify harms. Qualitative interviews and observations
      were used to understand mechanisms and effects. RESULTS: RATE OF HARMS IN
      PATIENTS FOR WHOM THERE WAS A DOCUMENTED DECISION NOT TO ATTEMPT CPR WAS REDUCED:
      Rate difference per 1000 patient-days was 12.9 (95% CI: 2.6-23.2, p-value=0.01).
      There was a difference in the proportion of harms contributing to patient death
      in the two periods (23/71 in the DNACPR period to 4/44 in the UFTO period (95% CI
      7.8-36.1, p-value=0.006). Significant differences were maintained after
      adjustment for known confounders. No significant change was seen on
      contemporaneous case control wards. Interviews with clinicians and observation of
      ward practice revealed the UFTO helped provide clarity of goals of care and
      reduced negative associations with resuscitation decisions. CONCLUSIONS:
      Introducing the UFTO was associated with a significant reduction in harmful
      events in patients in whom a decision not to attempt CPR had been made. Coupled
      with supportive qualitative evidence, this indicates the UFTO improved care for
      this vulnerable group. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN85474986
      UK Comprehensive Research Network Portfolio 7932.

PMID- 24023719
TI  - Genomic, proteomic, and biochemical analyses of oleaginous Mucor circinelloides:
      evaluating its capability in utilizing cellulolytic substrates for lipid
      production.
AB  - Lipid production by oleaginous microorganisms is a promising route to produce raw
      material for the production of biodiesel. However, most of these organisms must
      be grown on sugars and agro-industrial wastes because they cannot directly
      utilize lignocellulosic substrates. We report the first comprehensive
      investigation of Mucor circinelloides, one of a few oleaginous fungi for which
      genome sequences are available, for its potential to assimilate cellulose and
      produce lipids. Our genomic analysis revealed the existence of genes encoding 13
      endoglucanases (7 of them secretory), 3 beta-D-glucosidases (2 of them secretory)
      and 243 other glycoside hydrolase (GH) proteins, but not genes for exoglucanases
      such as cellobiohydrolases (CBH) that are required for breakdown of cellulose to
      cellobiose. Analysis of the major PAGE gel bands of secretome proteins confirmed
      expression of two secretory endoglucanases and one beta-D-glucosidase, along with
      a set of accessory cell wall-degrading enzymes and 11 proteins of unknown
      function. We found that M. circinelloides can grow on CMC (carboxymethyl
      cellulose) and cellobiose, confirming the enzymatic activities of endoglucanases
      and beta-D-glucosidases, respectively. The data suggested that M. circinelloides
      could be made usable as a consolidated bioprocessing (CBP) strain by introducing
      a CBH (e.g. CBHI) into the microorganism. This proposal was validated by our
      demonstration that M. circinelloides growing on Avicel supplemented with CBHI
      produced about 33% of the lipid that was generated in glucose medium.
      Furthermore, fatty acid methyl ester (FAME) analysis showed that when growing on
      pre-saccharified Avicel substrates, it produced a higher proportion of C14 fatty
      acids, which has an interesting implication in that shorter fatty acid chains
      have characteristics that are ideal for use in jet fuel. This substrate-specific
      shift in FAME profile warrants further investigation. 

PMID- 24023721
TI  - Characterization of phenotypes of immune cells and cytokines associated with
      chronic exposure to Premolis semirufa caterpillar bristles extract.
AB  - The Brazilian moth Premolis semirufa (Walker, 1856), usually called pararama, is
      a parasite of the rubber Hevea genus. Contact with the bristles causes symptoms
      of acute inflammation. A chronic inflammatory reaction frequently occurs in
      individuals after multiple contacts, and this reaction is characterised by
      articular synovial membrane thickening with joint deformities, common
      characteristics of chronic synovitis. Extract from the bristles has been shown to
      induce an intense inflammatory response in a murine model, and this reaction was
      characterised by the presence of neutrophils in the paw tissues of injected mice
      and a strong, specific antibody response. There is not yet an effective treatment
      for incidents involving contact with pararama. In this study, we evaluated the
      phenotype of the immunological response and cytokine production in BALB/c mice
      subcutaneously injected in the footpad with P. semirufa bristle extract or
      sterile saline (control) seven times at 15 day intervals. An analysis of cells
      from the draining lymph node by flow cytometry showed that the absolute numbers
      of TCD4, TCD8 and B lymphocytes, as well as the expression of activation
      molecules, were higher in the extract-treated group. Furthermore,
      immunohistochemistry and immunofluorescence analyses showed a mixed inflammatory
      infiltrate composed of neutrophils and macrophages at the inoculation site. In
      addition, an analysis of paw cytokines showed elevated levels of IL-6, IL-12, IL
      10, IL-17 and IL-23 after the 7(th) inoculation. In conclusion, these data
      provide evidence of pro-inflammatory changes in the phenotypes of immune cells
      and cytokine production in animals subjected to injections with an extract from
      Premolis semirufa bristles, which may explain the intense and prolonged
      inflammatory response that characterises this disorder. 

PMID- 24023720
TI  - Characterization of a mouse-adapted Staphylococcus aureus strain.
AB  - More effective antibiotics and a protective vaccine are desperately needed to
      combat the 'superbug' Staphylococcus aureus. While in vivo pathogenicity studies
      routinely involve infection of mice with human S. aureus isolates, recent genetic
      studies have demonstrated that S. aureus lineages are largely host-specific. The
      use of such animal-adapted S. aureus strains may therefore be a promising
      approach for developing more clinically relevant animal infection models. We have
      isolated a mouse-adapted S. aureus strain (JSNZ) which caused a severe outbreak
      of preputial gland abscesses among male C57BL/6J mice. We aimed to extensively
      characterize this strain on a genomic level and determine its virulence potential
      in murine colonization and infection models. JSNZ belongs to the MLST type ST88,
      rare among human isolates, and lacks an hlb-converting phage encoding human
      specific immune evasion factors. Naive mice were found to be more susceptible to
      nasal and gastrointestinal colonization with JSNZ than with the human-derived
      Newman strain. Furthermore, naive mice required antibiotic pre-treatment to
      become colonized with Newman. In contrast, JSNZ was able to colonize mice in the
      absence of antibiotic treatment suggesting that this strain can compete with the
      natural flora for space and nutrients. In a renal abscess model, JSNZ caused more
      severe disease than Newman with greater weight loss and bacterial burden. In
      contrast to most other clinical isolates, JSNZ can also be readily genetically
      modified by phage transduction and electroporation. In conclusion, the mouse
      adapted strain JSNZ may represent a valuable tool for studying aspects of mucosal
      colonization and for screening novel vaccines and therapies directed at
      preventing colonization. 

PMID- 24023722
TI  - Unique haploinsufficient role of the microRNA-processing molecule Dicer1 in a
      murine colitis-associated tumorigenesis model.
AB  - A widespread downregulated expression of microRNAs (miRNAs) is commonly observed
      in human cancers. Similarly, deregulated expression of miRNA-processing pathway
      components, which results in the reduction of global miRNA expression, may also
      be associated with tumorigenesis. Here, we show that specific ablation of Dicer1
      in intestinal epithelial cells accelerates intestinal inflammation-associated
      tumorigenesis. This effect was apparent only when a single copy of Dicer1 was
      deleted, but not with complete Dicer1 ablation. DICER expression and subsequent
      mature miRNA levels were inversely correlated with the number of intact Dicer1
      alleles. Because the expression levels of DICER were retained in tumors and its
      surrounding tissues even after induction of colitis-associated tumors, the
      effects of Dicer1 deletion were cell-autonomous. Although the expression levels
      of representative oncogenes and tumor suppressor genes were in most cases
      inversely correlated with the expression levels of DICER, some genes were not
      affected by Dicer1 deletion. Thus, deregulating the delicate balance between the
      expression levels of tumor-promoting and -suppressive genes may be crucial for
      tumorigenesis in this unique haploinsufficient case. 

PMID- 24023723
TI  - ERCC1 and ERCC2 variants predict survival in gastric cancer patients.
AB  - PURPOSE: ERCC1 and ERCC2 play critical roles in the nucleotide excision repair
      pathway that effectively repairs DNA damage induced by chemotherapeutic agents.
      Therefore, functional single nucleotide polymorphisms (SNPs) in these genes could
      have an impact on clinical outcomes in cancer patients who received chemotherapy.
      However, few studies have simultaneously investigated the roles of ERCC1 and
      ERCC2 SNPs in clinical outcomes in gastric cancer patients. EXPERIMENTAL DESIGN:
      We genotyped by the TaqMan assay three common, potentially functional ERCC1
      (rs3212986) and ERCC2 SNPs (rs13181 and rs1799793) in 360 gastric cancer
      patients. We used both Kaplan-Meier tests and Cox proportional hazards models to
      evaluate the effects of ERCC1 and ERCC2 genotypes and haplotypes on clinical
      outcomes. RESULTS: We found that, compared with ERCC2 rs1799793 GG+AG genotypes,
      the homozygous variant AA genotype was associated with significantly poorer
      overall survival (OS) (AA vs. GG+AG, log-rank P=0.012) and significantly higher
      risk of death (AA vs. GG+AG, Adjusted hazards ratio [HR] 2.13; 95% CI, 1.28 to
      3.56; P=0.004). In combined analyses, patients with any one of the three
      unfavorable genotypes (i.e. ERCC1 rs3212986 TT, ERCC2 rs13181 GG and rs1799793
      AA) had statistically significant hazards of poor prognosis (Adjusted HR, 1.54;
      95% CI, 1.06 to 2.25; P=0.025), compared with those without any unfavorable
      genotypes. Furthermore, the haplotype A-G-G (rs1799793/rs13181/rs3212986) had a
      significant impact on OS (Adjusted HR, 1.57; 95% CI, 1.11 to 2.21; P=0.011),
      compared with the common haplotype G-T-G. CONCLUSION: ERCC1 and ERCC2 functional
      SNPs may jointly affect OS in Caucasian gastric cancer patients. Additional large
      prospective studies are essential to confirm our findings.

PMID- 24023724
TI  - Model free approach to kinetic analysis of real-time hyperpolarized 13C magnetic
      resonance spectroscopy data.
AB  - Real-time detection of the rates of metabolic flux, or exchange rates of
      endogenous enzymatic reactions, is now feasible in biological systems using
      Dynamic Nuclear Polarization Magnetic Resonance. Derivation of reaction rate
      kinetics from this technique typically requires multi-compartmental modeling of
      dynamic data, and results are therefore model-dependent and prone to
      misinterpretation. We present a model-free formulism based on the ratio of total
      areas under the curve (AUC) of the injected and product metabolite, for example
      pyruvate and lactate. A theoretical framework to support this novel analysis
      approach is described, and demonstrates that the AUC ratio is proportional to the
      forward rate constant k. We show that the model-free approach strongly correlates
      with k for whole cell in vitro experiments across a range of cancer cell lines,
      and detects response in cells treated with the pan-class I PI3K inhibitor GDC
      0941 with comparable or greater sensitivity. The same result is seen in vivo with
      tumor xenograft-bearing mice, in control tumors and following drug treatment with
      dichloroacetate. An important finding is that the area under the curve is
      independent of both the input function and of any other metabolic pathways
      arising from the injected metabolite. This model-free approach provides a robust
      and clinically relevant alternative to kinetic model-based rate measurements in
      the clinical translation of hyperpolarized (13)C metabolic imaging in humans,
      where measurement of the input function can be problematic. 

PMID- 24023725
TI  - M1 muscarinic receptor activation mediates cell death in M1-HEK293 cells.
AB  - HEK293 cells have been used extensively to generate stable cell lines to study G
      protein-coupled receptors, such as muscarinic acetylcholine receptors (mAChRs).
      The activation of M1 mAChRs in various cell types in vitro has been shown to be
      protective. To further investigate M1 mAChR-mediated cell survival, we generated
      stable HEK293 cell-lines expressing the human M1 mAChR. M1 mAChRs were
      efficiently expressed at the cell surface and efficiently internalised within 1 h
      by carbachol. Carbachol also induced early signalling cascades similar to
      previous reports. Thus, ectopically expressed M1 receptors behaved in a similar
      fashion to the native receptor over short time periods of analysis. However,
      substantial cell death was observed in HEK293-M1 cells within 24 h after
      carbachol application. Death was only observed in HEK cells expressing M1
      receptors and fully blocked by M1 antagonists. M1 mAChR-stimulation mediated
      prolonged activation of the MEK-ERK pathway and resulted in prolonged induction
      of the transcription factor EGR-1 (>24 h). Blockade of ERK signalling with U0126
      did not reduce M1 mAChR-mediated cell-death significantly but inhibited the acute
      induction of EGR-1. We investigated the time-course of cell death using time
      lapse microscopy and xCELLigence technology. Both revealed the M1 mAChR
      cytotoxicity occurs within several hours of M1 activation. The xCELLigence assay
      also confirmed that the ERK pathway was not involved in cell-death.
      Interestingly, the MEK blocker did reduce carbachol-mediated cleaved caspase 3
      expression in HEK293-M1 cells. The HEK293 cell line is a widely used
      pharmacological tool for studying G-protein coupled receptors, including mAChRs.
      Our results highlight the importance of investigating the longer term fate of
      these cells in short term signalling studies. Identifying how and why activation
      of the M1 mAChR signals apoptosis in these cells may lead to a better
      understanding of how mAChRs regulate cell-fate decisions. 

PMID- 24023726
TI  - Diagnostic accuracy of microscopic Observation Drug Susceptibility (MODS) assay
      for pediatric tuberculosis in Hanoi, Vietnam.
AB  - INTRODUCTION: Microscopic [corrected] Observation Drug Susceptibility (MODS) has
      been shown to be an effective and rapid technique for early diagnosis of
      tuberculosis (TB). Thus far only a limited number of studies evaluating MODS have
      been performed in children and in extra-pulmonary tuberculosis. This study aims
      to assess relative accuracy and time to positive culture of MODS for TB diagnosis
      in children admitted to a general pediatric hospital in Vietnam.
      METHODS/PRINCIPAL FINDINGS: Specimens from children with suspected TB were tested
      by smear, MODS and Lowenstein-Jensen agar (LJ). 1129 samples from 705 children
      were analyzed, including sputum (n=59), gastric aspirate (n=775), CSF (n=148),
      pleural fluid (n=33), BAL (n=41), tracheal fluid (n=45), other (n=28). 113 TB
      cases were defined based on the "clinical diagnosis" (confirmed and probable
      groups) as the reference standard, in which 26% (n=30) were diagnosed as extra
      pulmonary TB. Analysis by patient shows that the overall sensitivity and
      specificity of smear, LJ and MODS against "clinical diagnosis" was 8.8% and 100%,
      38.9% and 100%, 46% and 99.5% respectively with MODS significantly more sensitive
      than LJ culture (P=0.02). When analyzed by sample type, the sensitivity of MODS
      was significantly higher than LJ for gastric aspirates (P=0.004). The time to
      detection was also significantly shorter for MODS than LJ (7 days versus 32 days,
      P<0.001). CONCLUSION: MODS [corrected] is a sensitive and rapid culture technique
      for detecting TB in children. As MODS culture can be performed at a BSL2 facility
      and is inexpensive, it can therefore be recommended as a routine test for
      children with symptoms suggestive of TB in resource-limited settings.

PMID- 24023727
TI  - Metformin inhibits angiotensin II-induced differentiation of cardiac fibroblasts
      into myofibroblasts.
AB  - Differentiation of cardiac fibroblasts into myofibroblasts is a critical event in
      the progression of cardiac fibrosis that leads to pathological cardiac
      remodeling. Metformin, an antidiabetic agent, exhibits a number of
      cardioprotective properties. However, much less is known regarding the effect of
      metformin on cardiac fibroblast differentiation. Thus, in the present study, we
      examined the effect of metformin on angiotensin (Ang) II-induced differentiation
      of cardiac fibroblasts into myofibroblasts and its underlying mechanism. Adult
      rat cardiac fibroblasts were stimulated with Ang II (100 nM) in the presence or
      absence of metformin (10-200 uM). Ang II stimulation induced the differentiation
      of cardiac fibroblasts into myofibroblasts, as indicated by increased expression
      of alpha-smooth muscle actin (alpha-SMA) and collagen types I and III, and this
      effect of Ang II was inhibited by pretreatment of cardiac fibroblasts with
      metformin. Metformin also decreased Ang II-induced reactive oxygen species (ROS)
      generation in cardiac fibroblasts via inhibiting the activation of the PKC-NADPH
      oxidase pathway. Further experiments using PKC inhibitor calphostin C and NADPH
      oxidase inhibitor apocynin confirmed that inhibition of the PKC-NADPH oxidase
      pathway markedly attenuated Ang II-induced ROS generation and myofibroblast
      differentiation. These data indicate that metformin inhibits Ang II-induced
      myofibroblast differentiation by suppressing ROS generation via the inhibition of
      the PKC-NADPH oxidase pathway in adult rat cardiac fibroblasts. Our results
      provide new mechanistic insights regarding the cardioprotective effects of
      metformin and provide an efficient therapeutic strategy to attenuate cardiac
      fibrosis. 

PMID- 24023728
TI  - Inhibitory effect of metformin and pyridoxamine in the formation of early,
      intermediate and advanced glycation end-products.
AB  - BACKGROUND: Non-enzymatic glycation is the addition of free carbonyl group of
      reducing sugar to the free amino groups of proteins, resulting in the formation
      of a Schiff base and an Amadori product. Dihydroxyacetone (DHA) is one of the
      carbonyl species which reacts rapidly with the free amino groups of proteins to
      form advanced glycation end products (AGEs). The highly reactive dihydroxyacetone
      phosphate is a derivative of dihydroxyacetone (DHA), and a product of glycolysis,
      having potential glycating effects to form AGEs. The formation of AGEs results in
      the generation of free radicals which play an important role in the
      pathophysiology of aging and diabetic complications. While the formation of DHA
      AGEs has been demonstrated previously, no extensive studies have been performed
      to assess the inhibition of AGE inhibitors at all the three stages of glycation
      (early, intermediate and late) using metformin (MF) and pyridoxamine (PM) as a
      novel inhibitor. METHODOLOGY/PRINCIPAL FINDINGS: In this study we report
      glycation of human serum albumin (HSA) & its characterization by various
      spectroscopic techniques. Furthermore, inhibition of glycation products at all
      the stages of glycation was also studied. Spectroscopic analysis suggests
      structural perturbations in the HSA as a result of modification which might be
      due to generation of free radicals and formation of AGEs. CONCLUSION: The
      inhibition in the formation of glycation reaction reveals that Pyridoxamine is a
      better antiglycating agent than Metformin at all stages of the glycation (early,
      intermediate and late stages).

PMID- 24023729
TI  - Type-specific cell line models for type-specific ovarian cancer research.
AB  - BACKGROUND: OVARIAN CARCINOMAS CONSIST OF AT LEAST FIVE DISTINCT DISEASES: high
      grade serous, low-grade serous, clear cell, endometrioid, and mucinous. Biomarker
      and molecular characterization may represent a more biologically relevant basis
      for grouping and treating this family of tumors, rather than site of origin.
      Molecular characteristics have become the new standard for clinical pathology,
      however development of tailored type-specific therapies is hampered by a failure
      of basic research to recognize that model systems used to study these diseases
      must also be stratified. Unrelated model systems do offer value for study of
      biochemical processes but specific cellular context needs to be applied to assess
      relevant therapeutic strategies. METHODS: We have focused on the identification
      of clear cell carcinoma cell line models. A panel of 32 "ovarian cancer" cell
      lines has been classified into histotypes using a combination of mutation
      profiles, IHC mutation-surrogates, and a validated immunohistochemical model. All
      cell lines were identity verified using STR analysis. RESULTS: Many described
      ovarian clear cell lines have characteristic mutations (including ARID1A and
      PIK3CA) and an overall molecular/immuno-profile typical of primary tumors.
      Mutations in TP53 were present in the majority of high-grade serous cell lines.
      Advanced genomic analysis of bona-fide clear cell carcinoma cell lines also
      support copy number changes in typical biomarkers such at MET and HNF1B and a
      lack of any recurrent expressed re-arrangements. CONCLUSIONS: As with primary
      ovarian tumors, mutation status of cancer genes like ARID1A and TP53 and a
      general immuno-profile serve well for establishing histotype of ovarian cancer
      cell We describe specific biomarkers and molecular features to re-classify
      generic "ovarian carcinoma" cell lines into type specific categories. Our data
      supports the use of prototype clear cell lines, such as TOV21G and JHOC-5, and
      questions the use of SKOV3 and A2780 as models of high-grade serous carcinoma.

PMID- 24023731
TI  - miR-346 regulates osteogenic differentiation of human bone marrow-derived
      mesenchymal stem cells by targeting the Wnt/beta-catenin pathway.
AB  - Osteogenic differentiation of human mesenchymal stem cells (hMSCs) is regulated
      by multiple transcription factors and signaling molecules. However, the molecular
      mechanisms underlying this process remain to be fully elucidated. MicroRNAs
      (miRNAs) act as key regulators in various biological processes by mediating mRNA
      degradation or translational inhibition of target genes. In this study, we report
      that miR-346 plays critical roles in regulating osteogenic differentiation of
      hBMSCs. The expression of endogenous miR-346 was increased during osteogenic
      differentiation of hBMSCs. Overexpression of miR-346 significantly promoted
      osteogenic differentiation, whereas miR-346 depletion suppressed this process.
      Further studies confirmed that miR-346 directly targeted the 3'-UTR of the
      glycogen synthase kinase-3beta (GSK-3beta) gene so as to suppress the expression
      of GSK-3beta protein. Similar to miR-346 overexpression, GSK-3beta depletion
      promoted osteogenic differentiation, whereas GSK-3beta overexpression reversed
      the promotional effect of miR-346. We further found that miR-346 overexpression
      activated the Wnt/beta-catenin pathway and increased the expression of several
      downstream genes including CyclinD1, c-Myc, TCF-1 and LEF-1. Depletion of beta
      catenin almost completely blocked the positive role of miR-346 on osteogenic
      differentiation. Taken together, our data indicate that miR-346 positively
      regulates hBMSC osteogenic differentiation by targeting GSK-3beta and activating
      the Wnt/beta-catenin pathway. 

PMID- 24023730
TI  - Different factors associated with CTX-M-producing ST131 and non-ST131 Escherichia
      coli clinical isolates.
AB  - OBJECTIVES: To determine factors associated with CTX-M-producing ST131
      Escherichia coli which is the worldwide predominant lineage among CTX-M-producing
      E. coli isolates. METHODS: Consecutive inpatients with a clinical sample positive
      for CTX-M-producing E. coli and considered as cases in a previous 8-month (2008
      2009) case-control study performed in ten university hospitals in the Paris area
      were included in the present sub-population study. Patients with a CTX-M
      producing ST131 E. coli clinical isolate were compared with those with a CTX-M
      producing non-ST131 E. coli clinical isolate with regard to 66 variables.
      Variables were first compared using univariate logistic regression, then a
      multivariate analysis using a backward selection with variables with p-value <0.1
      in univariate analysis was carried out. RESULTS: Fifty-five patients with a CTX-M
      producing ST131 E. coli clinical isolate were compared to 97 patients with a CTX
      producing non-ST131 E. coli clinical isolate. Multivariate analysis showed that
      only previous residence in long term care facilities (OR=4.4; 95% CI=1.3-14.7)
      was positively associated with a CTX-M-producing ST131 E. coli isolate. However,
      it also showed that regular consumption of poultry products (OR=0.2; 95% CI=0.1
      0.6), having had at least one device in the preceding 6 months (OR=0.3; 95%
      CI=0.1-0.7) and stay in ICU (OR=0.2; 95% CI=0.05-0.8) were negatively associated
      with isolation of CTX-M-producing ST131 E. coli from clinical samples.
      CONCLUSIONS: This study provides more insight into the epidemiological features
      of ST131 and non-ST131 E. coli producing CTX-M enzymes. It shows, for the first
      time, that isolation of CTX-M-producing ST131 E. coli from clinical samples is
      not linked to consumption of various foods and confirms that residence in long
      term care facilities is a predictor of these isolates.

PMID- 24023732
TI  - Molecular dynamics simulations of water/mucus partition coefficients for feeding
      stimulants in fish and the implications for olfaction.
AB  - The odorant partition coefficient is a physicochemical property that has been
      shown to dramatically influence odorant deposition patterns in the mammalian
      nose, leading to a chromatographic separation of odorants along the sensory
      epithelium. It is unknown whether a similar phenomenon occurs in fish. Here we
      utilize molecular dynamics simulations, based on a simplified molecular model of
      olfactory mucus, to calculate water/mucus partition coefficients for amino acid
      odorants (alanine, glycine, cysteine, and valine) that are known to elicit
      feeding behavior in fish. Both fresh water and salt water environments are
      considered. In fresh water, all four amino acids prefer the olfactory mucus phase
      to water, and the partition coefficient is shown to correlate with amino acid
      hydrophobicity. In salt water, a reversal in odorant partitioning is found, where
      each of the feeding stimulants (except glycine) prefer the water phase to
      olfactory mucus. This is due to the interactions between the salt ions and the
      odorant molecules (in the water phase), and between the salt and simplified mucin
      (in the olfactory mucus phase). Thus, slightly different odorant deposition
      patterns may occur in the fish olfactory organ in fresh and salt water
      environments. However, in both underwater environments we found that the
      variation of the water/mucus odorant partition coefficient is approximately one
      order of magnitude, in stark contrast to air/mucus odorant partition coefficients
      that can span up to six orders of magnitude. We therefore anticipate relatively
      similar deposition patterns for most amino acid odorants in the fish olfactory
      chamber. Thus, in contrast to terrestrial species, living in an underwater
      environment may preclude appreciable chromatographic odorant separation that may
      be used for spatial coding of odor identity across the olfactory epithelium. This
      is consistent with the reported lack of spatial organization of olfactory
      receptor neurons in the fish olfactory epithelium. 

PMID- 24023733
TI  - Cyclic peptide inhibitors of the beta-sliding clamp in Staphylococcus aureus.
AB  - Interaction between pairs of Staphylococcus aureus replication proteins was
      detected in an Escherichia coli based two-hybrid analysis. A reverse two-hybrid
      system was constructed for selection of compounds that hindered interaction
      between interacting protein pairs. A number of cyclic peptides, from a library
      generated by the split intein-mediated circular ligation of peptides and proteins
      technology, were found to interfere with dimerization of the beta-sliding clamp
      of the replisome. Two 8-mer peptides were analyzed in more detail. Both inhibited
      DNA replication, led to SOS induction, altered cell morphology and cell death.
      The peptides were active when added to bacterial cultures indicating that they
      could traverse the bacterial membrane to find their intracellular target. Peptide
      specificity was confirmed by overproduction of the putative target (DnaN) which
      resulted in resistance. The minimum inhibitory concentration was ~50 MUg/ml for
      S. aureus cells. These compounds may serve as lead candidates for future
      development into novel classes of antibiotics as well as provide information on
      the function of the S. aureus replication process. 

PMID- 24023734
TI  - Repressive effect of primary virus replication on superinfection correlated with
      gut-derived central memory CD4(+) T cells in SHIV-infected Chinese rhesus
      macaques.
AB  - A possible mechanism of susceptibility to superinfection with simian-human
      immunodeficiency virus (SHIV)-1157ipd3N4 was explored in twelve SHIVSF162P3
      infected Chinese rhesus macaques. Based on the kinetics of viral replication for
      the second infecting virus following SHIV-1157ipd3N4 inoculation, the monkeys
      were divided into two groups: those relatively resistant to superinfection (SIR)
      and those relatively sensitive to superinfection (SIS). We found that
      superinfection-resistant macaques had high primary viremia, whereas
      superinfection-sensitive macaques had low primary viremia, suggesting that
      primary SHIVSF162P3 infection with a high viral-replication level would repress
      superinfection with a heterologous SHIV-1157ipd3N4. Although no correlation of
      protection against superinfection with virus-specific CD4(+) T cell or CD8(+) T
      cell immune responses from gut was observed prior to superinfection,
      superinfection susceptibility was strongly correlated with CD4(+) Tcm cells from
      gut both prior to the second infecting virus inoculation and on day 7 after
      superinfection, but not with CD4(+) Tem cells from gut or with CD4(+) Tcm cells
      from peripheral blood and lymph node. These results point to the important roles
      of gut-derived CD4(+) Tcm cells for the study of the mechanisms of protection
      against superinfection and the evaluation of the safety and efficacy of vaccines
      and therapies against acquired immune deficiency syndrome (AIDS). 

PMID- 24023735
TI  - Dynamics of DNA damage induced pathways to cancer.
AB  - Chemotherapy is commonly used in cancer treatments, however only 25% of cancers
      are responsive and a significant proportion develops resistance. The p53 tumour
      suppressor is crucial for cancer development and therapy, but has been less
      amenable to therapeutic applications due to the complexity of its action,
      reflected in 66,000 papers describing its function. Here we provide a systematic
      approach to integrate this information by constructing a large-scale logical
      model of the p53 interactome using extensive database and literature integration.
      The model contains 206 nodes representing genes or proteins, DNA damage input,
      apoptosis and cellular senescence outputs, connected by 738 logical interactions.
      Predictions from in silico knock-outs and steady state model analysis were
      validated using literature searches and in vitro based experiments. We identify
      an upregulation of Chk1, ATM and ATR pathways in p53 negative cells and 61 other
      predictions obtained by knockout tests mimicking mutations. The comparison of
      model simulations with microarray data demonstrated a significant rate of
      successful predictions ranging between 52% and 71% depending on the cancer type.
      Growth factors and receptors FGF2, IGF1R, PDGFRB and TGFA were identified as
      factors contributing selectively to the control of U2OS osteosarcoma and HCT116
      colon cancer cell growth. In summary, we provide the proof of principle that this
      versatile and predictive model has vast potential for use in cancer treatment by
      identifying pathways in individual patients that contribute to tumour growth,
      defining a sub population of "high" responders and identification of shifts in
      pathways leading to chemotherapy resistance. 

PMID- 24023736
TI  - Unique association between global DNA hypomethylation and chromosomal alterations
      in human hepatocellular carcinoma.
AB  - Global DNA hypomethylation is a characteristic feature of cancer cells that
      closely associates with chromosomal instability (CIN). However, the association
      between these characteristics during hepatocarcinogenesis remains unclear.
      Herein, we determined the relationship between hypomethylation and CIN in human
      hepatocellular carcinoma (HCC) by analyzing 179 HCCs, 178 matched non-tumor
      livers and 23 normal liver tissues. Hypomethylation at three different repetitive
      DNA (rDNA) sequences and hypermethylation of 12 CpG loci, including 11 tumor
      suppressor gene (TSG) promoters, were quantified using MethyLight or combined
      bisulfite restriction analysis. Fractional allelic loss (FAL) was used as a
      marker for CIN, calculated by analyzing 400 microsatellite markers. Gains and
      losses at each chromosome were also determined using semi-quantitative
      microsatellite analysis. The associations between rDNA hypomethylation and FAL,
      as well as between TSG hypermethylation and FAL were investigated. Significantly
      more hypomethylation was observed in HCC tissues than in normal liver samples.
      Progression of hypomethylation during carcinogenesis was more prominent in
      hepatitis C virus (HCV)-negative cases, which was in contrast to our previous
      reports of significantly increased TSG methylation levels in HCV-positive tumors.
      Absence of liver cirrhosis and higher FAL scores were identified as independent
      contributors to significant hypomethylation of rDNA in HCC. Among the chromosomal
      alterations frequently observed in HCC, loss of 8p, which was unique in the
      earliest stages of hepatocarcinogenesis, was significantly associated with
      hypomethylation of rDNA by multivariable analysis (p=0.0153). rDNA
      hypomethylation was also associated with a high FAL score regardless of tumor
      differentiation (p=0.0011, well-differentiated; p=0.0089, moderately/poorly
      differentiated HCCs). We conclude that DNA hypomethylation is an important cause
      of CIN in the earliest step of HCC, especially in a background of non-cirrhotic
      liver.

PMID- 24023737
TI  - Elucidation of toxicity pathways in lung epithelial cells induced by silicon
      dioxide nanoparticles.
AB  - A study into the effects of amorphous nano-SiO2 particles on A549 lung epithelial
      cells was undertaken using proteomics to understand the interactions that occur
      and the biological consequences of exposure of lung to nanoparticles. Suitable
      conditions for treatment, where A549 cells remained viable for the exposure
      period, were established by following changes in cell morphology, flow cytometry,
      and MTT reduction. Label-free proteomics was used to estimate the relative level
      of proteins from their component tryptic peptides detected by mass spectrometry.
      It was found that A549 cells tolerated treatment with 100 ug/ml nano-SiO2 in the
      presence of 1.25% serum for at least 4 h. After this time detrimental changes in
      cell morphology, flow cytometry, and MTT reduction were evident. Proteomics
      performed after 4 h indicated changes in the expression of 47 proteins. Most of
      the proteins affected fell into four functional groups, indicating that the most
      prominent cellular changes were those that affected apoptosis regulation (e.g.
      UCP2 and calpain-12), structural reorganisation and regulation of actin
      cytoskeleton (e.g. PHACTR1), the unfolded protein response (e.g. HSP 90), and
      proteins involved in protein synthesis (e.g. ribosomal proteins). Treatment with
      just 10 ug/ml nano-SiO2 particles in serum-free medium resulted in a rapid
      deterioration of the cells and in medium containing 10% serum the cells were
      resistant to up to 1000 ug/ml nano-SiO2 particles, suggesting interaction of
      serum components with the nanoparticles. A variety of serum proteins were found
      which bound to nano-SiO2 particles, the most prominent of which were albumin,
      apolipoprotein A-I, hemoglobin, vitronectin and fibronectin. The use of a
      proteomics platform, with appropriately designed experimental conditions, enabled
      the early biological perturbations induced by nano-SiO2 in a model target cell
      system to be identified. The approach facilitates the design of more focused test
      systems for use in tiered evaluations of nanomaterials. 

PMID- 24023738
TI  - A metastable equilibrium model for the relative abundances of microbial phyla in
      a hot spring.
AB  - Many studies link the compositions of microbial communities to their
      environments, but the energetics of organism-specific biomass synthesis as a
      function of geochemical variables have rarely been assessed. We describe a
      thermodynamic model that integrates geochemical and metagenomic data for biofilms
      sampled at five sites along a thermal and chemical gradient in the outflow
      channel of the hot spring known as "Bison Pool" in Yellowstone National Park. The
      relative abundances of major phyla in individual communities sampled along the
      outflow channel are modeled by computing metastable equilibrium among model
      proteins with amino acid compositions derived from metagenomic sequences.
      Geochemical conditions are represented by temperature and activities of basis
      species, including pH and oxidation-reduction potential quantified as the
      activity of dissolved hydrogen. By adjusting the activity of hydrogen, the model
      can be tuned to closely approximate the relative abundances of the phyla observed
      in the community profiles generated from BLAST assignments. The findings reveal
      an inverse relationship between the energy demand to form the proteins at equal
      thermodynamic activities and the abundance of phyla in the community. The
      distance from metastable equilibrium of the communities, assessed using an
      equation derived from energetic considerations that is also consistent with the
      information-theoretic entropy change, decreases along the outflow channel.
      Specific divergences from metastable equilibrium, such as an underprediction of
      the relative abundances of phototrophic organisms at lower temperatures, can be
      explained by considering additional sources of energy and/or differences in
      growth efficiency. Although the metabolisms used by many members of these
      communities are driven by chemical disequilibria, the results support the
      possibility that higher-level patterns of chemotrophic microbial ecosystems are
      shaped by metastable equilibrium states that depend on both the composition of
      biomass and the environmental conditions. 

PMID- 24023739
TI  - Epigenetic regulation of pluripotent genes mediates stem cell features in human
      hepatocellular carcinoma and cancer cell lines.
AB  - Activation of the stem cell transcriptional circuitry is an important event in
      cancer development. Although cancer cells demonstrate a stem cell-like gene
      expression signature, the epigenetic regulation of pluripotency-associated genes
      in cancers remains poorly understood. In this study, we characterized the
      epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC,
      KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples,
      and investigated the re-activation of pluripotency regulatory circuits in cancer
      progression. Differential patterns of DNA methylation, histone modifications, and
      gene expression of pluripotent genes were demonstrated in different types of
      cancers, which may reflect their tissue origins. NANOG promoter hypomethylation
      and gene upregulation were found in metastatic human liver cancer cells and human
      hepatocellular carcinoma (HCC) primary tumor tissues. The upregulation of NANOG,
      together with p53 depletion, was significantly associated with clinical late
      stage of HCC. A pro-metastatic role of NANOG in colon cancer cells was also
      demonstrated, using a NANOG-overexpressing orthotopic tumor implantation mouse
      model. Demethylation of NANOG promoter was observed in CD133+(high) cancer cells.
      In accordance, overexpression of NANOG resulted in an increase in the population
      of CD133+(high) cells. In addition, we demonstrated a cross-regulation between
      OCT4 and NANOG in cancer cells via reprogramming of promoter methylation. Taken
      together, epigenetic reprogramming of NANOG can lead to the acquisition of stem
      cell-like properties. These results underscore the restoration of pluripotency
      circuits in cancer cells as a potential mechanism for cancer progression. 

PMID- 24023740
TI  - Joint action syntax in Japanese martial arts.
AB  - Participation in interpersonal competitions, such as fencing or Japanese martial
      arts, requires players to make instantaneous decisions and execute appropriate
      motor behaviors in response to various situations. Such actions can be understood
      as complex phenomena emerging from simple principles. We examined the intentional
      switching dynamics associated with continuous movement during interpersonal
      competition in terms of their emergence from a simple syntax. Linear functions on
      return maps identified two attractors as well as the transitions between them.
      The effects of skill differences were evident in the second- and third-order
      state-transition diagrams for these two attractors. Our results suggest that
      abrupt switching between attractors is related to the diverse continuous
      movements resulting from quick responses to sudden changes in the environment.
      This abrupt-switching-quick-response behavior is characterized by a joint action
      syntax. The resulting hybrid dynamical system is composed of a higher module with
      discrete dynamics and a lower module with continuous dynamics. Our results
      suggest that intelligent human behavior and robust autonomy in real-life
      scenarios are based on this hybrid dynamical system, which connects interpersonal
      coordination and competition. 

PMID- 24023741
TI  - Insights into the loblolly pine genome: characterization of BAC and fosmid
      sequences.
AB  - Despite their prevalence and importance, the genome sequences of loblolly pine,
      Norway spruce, and white spruce, three ecologically and economically important
      conifer species, are just becoming available to the research community. Following
      the completion of these large assemblies, annotation efforts will be undertaken
      to characterize the reference sequences. Accurate annotation of these ancient
      genomes would be aided by a comprehensive repeat library; however, few studies
      have generated enough sequence to fully evaluate and catalog their non-genic
      content. In this paper, two sets of loblolly pine genomic sequence, 103
      previously assembled BACs and 90,954 newly sequenced and assembled fosmid
      scaffolds, were analyzed. Together, this sequence represents 280 Mbp (roughly 1%
      of the loblolly pine genome) and one of the most comprehensive studies of
      repetitive elements and genes in a gymnosperm species. A combination of homology
      and de novo methodologies were applied to identify both conserved and novel
      repeats. Similarity analysis estimated a repetitive content of 27% that included
      both full and partial elements. When combined with the de novo investigation, the
      estimate increased to almost 86%. Over 60% of the repetitive sequence consists of
      full or partial LTR (long terminal repeat) retrotransposons. Through de novo
      approaches, 6,270 novel, full-length transposable element families and 9,415 sub
      families were identified. Among those 6,270 families, 82% were annotated as
      single-copy. Several of the novel, high-copy families are described here, with
      the largest, PtPiedmont, comprising 133 full-length copies. In addition to
      repeats, analysis of the coding region reported 23 full-length eukaryotic
      orthologous proteins (KOGS) and another 29 novel or orthologous genes. These
      discoveries, along with other genomic resources, will be used to annotate conifer
      genomes and address long-standing questions about gymnosperm evolution. 

PMID- 24023742
TI  - Contact tracing of tuberculosis: a systematic review of transmission modelling
      studies.
AB  - The WHO recommended intervention of Directly Observed Treatment, Short-course
      (DOTS) appears to have been less successful than expected in reducing the burden
      of TB in some high prevalence settings. One strategy for enhancing DOTS is
      incorporating active case-finding through screening contacts of TB patients as
      widely used in low-prevalence settings. Predictive models that incorporate
      population-level effects on transmission provide one means of predicting impacts
      of such interventions. We aim to identify all TB transmission modelling studies
      addressing contact tracing and to describe and critically assess their modelling
      assumptions, parameter choices and relevance to policy. We searched MEDLINE,
      SCOPUS, COMPENDEX, Google Scholar and Web of Science databases for relevant
      English language publications up to February 2012. Of the 1285 studies
      identified, only 5 studies met our inclusion criteria of models of TB
      transmission dynamics in human populations designed to incorporate contact
      tracing as an intervention. Detailed implementation of contact processes was only
      present in two studies, while only one study presented a model for a high
      prevalence, developing world setting. Some use of relevant data for parameter
      estimation was made in each study however validation of the predicted impact of
      interventions was not attempted in any of the studies. Despite a large body of
      literature on TB transmission modelling, few published studies incorporate
      contact tracing. There is considerable scope for future analyses to make better
      use of data and to apply individual based models to facilitate more realistic
      patterns of infectious contact. Combined with a focus on high burden settings
      this would greatly increase the potential for models to inform the use of
      contract tracing as a TB control policy. Our findings highlight the potential for
      collaborative work between clinicians, epidemiologists and modellers to gather
      data required to enhance model development and validation and hence better inform
      future public health policy. 

PMID- 24023743
TI  - Therapeutic targeting of tumor growth and angiogenesis with a novel anti-S100A4
      monoclonal antibody.
AB  - S100A4, a member of the S100 calcium-binding protein family secreted by tumor and
      stromal cells, supports tumorigenesis by stimulating angiogenesis. We
      demonstrated that S100A4 synergizes with vascular endothelial growth factor
      (VEGF), via the RAGE receptor, in promoting endothelial cell migration by
      increasing KDR expression and MMP-9 activity. In vivo overexpression of S100A4
      led to a significant increase in tumor growth and vascularization in a human
      melanoma xenograft M21 model. Conversely, when silencing S100A4 by shRNA
      technology, a dramatic decrease in tumor development of the pancreatic MiaPACA-2
      cell line was observed. Based on these results we developed 5C3, a neutralizing
      monoclonal antibody against S100A4. This antibody abolished endothelial cell
      migration, tumor growth and angiogenesis in immunodeficient mouse xenograft
      models of MiaPACA-2 and M21-S100A4 cells. It is concluded that extracellular
      S100A4 inhibition is an attractive approach for the treatment of human cancer. 

PMID- 24023744
TI  - Authorship bias in violence risk assessment? A systematic review and meta
      analysis.
AB  - Various financial and non-financial conflicts of interests have been shown to
      influence the reporting of research findings, particularly in clinical medicine.
      In this study, we examine whether this extends to prognostic instruments designed
      to assess violence risk. Such instruments have increasingly become a routine part
      of clinical practice in mental health and criminal justice settings. The present
      meta-analysis investigated whether an authorship effect exists in the violence
      risk assessment literature by comparing predictive accuracy outcomes in studies
      where the individuals who designed these instruments were study authors with
      independent investigations. A systematic search from 1966 to 2011 was conducted
      using PsycINFO, EMBASE, MEDLINE, and US National Criminal Justice Reference
      Service Abstracts to identify predictive validity studies for the nine most
      commonly used risk assessment tools. Tabular data from 83 studies comprising 104
      samples was collected, information on two-thirds of which was received directly
      from study authors for the review. Random effects subgroup analysis and
      metaregression were used to explore evidence of an authorship effect. We found a
      substantial and statistically significant authorship effect. Overall, studies
      authored by tool designers reported predictive validity findings around two times
      higher those of investigations reported by independent authors (DOR=6.22 [95%
      CI=4.68-8.26] in designers' studies vs. DOR=3.08 [95% CI=2.45-3.88] in
      independent studies). As there was evidence of an authorship effect, we also
      examined disclosure rates. None of the 25 studies where tool designers or
      translators were also study authors published a conflict of interest statement to
      that effect, despite a number of journals requiring that potential conflicts be
      disclosed. The field of risk assessment would benefit from routine disclosure and
      registration of research studies. The extent to which similar conflict of
      interests exists in those developing risk assessment guidelines and providing
      expert testimony needs clarification.

PMID- 24023745
TI  - From understanding to appreciating music cross-culturally.
AB  - It has long been debated which aspects of music perception are universal and
      which are developed only after exposure to a specific musical culture. Here we
      investigated whether "iconic" meaning in Western music, emerging from musical
      information resembling qualities of objects, or qualities of abstract concepts,
      can be recognized cross-culturally. To this end we acquired a profile of semantic
      associations (such as, for example, fight, river, etc.) to Western musical pieces
      from each participant, and then compared these profiles across cultural groups.
      Results show that the association profiles between Mafa, an ethnic group from
      northern Cameroon, and Western listeners are different, but that the Mafa have a
      consistent association profile, indicating that their associations are strongly
      informed by their enculturation. Results also show that listeners for whom
      Western music is novel, but whose association profile was more similar to the
      mean Western music association profile also had a greater appreciation of the
      Western music. The data thus show that, to some degree, iconic meaning transcends
      cultural boundaries, with a high inter-individual variance, probably because
      meaning in music is prone to be overwritten by individual and cultural
      experience. 

PMID- 24023746
TI  - A novel insight on signal transduction mechanism of RcsCDB system in Salmonella
      enterica serovar typhimurium.
AB  - The RcsCDB system of Salmonella enterica serovar Typhimurium is implicated in the
      control of capsule and flagella synthesis. The hybrid sensor RcsC, the
      phosphotransferase RcsD and the RcsB regulator, constitute the main components of
      the RcsCDB system. The proposed Rcs signaling cascade involves the
      autophosphorylation of RcsC and the transfer of the phosphate group to RcsB,
      mediated by RcsD. We previously reported that the overexpression of rcsB repress
      the transcription of rcsD by an autoregulation mechanism. Moreover, we
      demonstrated that during the rcsD repression, the RcsB-dependent flagellar
      modulation remained active. These results suggest that the Rcs phosphorelay
      mechanism occurs even in the absence of RcsD. In this work, we established the
      existence of two alternative phosphorelay pathways driving activation of this
      system. We demonstrated that RcsC and RcsD can act as histidine kinase proteins
      which, after autophosphorylated, are able to independently transfer the phosphate
      to RcsB. Our results suggest that these pathways could be activated by different
      environmental signals, leading different levels of RcsB-phosphorylated to produce
      a differential gene modulation. These findings contribute to a better
      understanding of the complexity and importance of the Rcs system activation,
      where more than one phosphate flow pathway increases the possibilities to exert
      gene regulation for a quick environmental changes response. 

PMID- 24023747
TI  - Chimeric newcastle disease virus protects chickens against avian influenza in the
      presence of maternally derived NDV immunity.
AB  - Newcastle disease virus (NDV), an avian paramyxovirus type 1, is a promising
      vector for expression of heterologous proteins from a variety of unrelated
      viruses including highly pathogenic avian influenza virus (HPAIV). However, pre
      existing NDV antibodies may impair vector virus replication, resulting in an
      inefficient immune response against the foreign antigen. A chimeric NDV-based
      vector with functional surface glycoproteins unrelated to NDV could overcome this
      problem. Therefore, an NDV vector was constructed which carries the fusion (F)
      and hemagglutinin-neuraminidase (HN) proteins of avian paramyxovirus type 8 (APMV
      8) instead of the corresponding NDV proteins in an NDV backbone derived from the
      lentogenic NDV Clone 30 and a gene expressing HPAIV H5 inserted between the F and
      HN genes. After successful virus rescue by reverse genetics, the resulting
      chNDVFHN PMV8H5 was characterized in vitro and in vivo. Expression and virion
      incorporation of the heterologous proteins was verified by Western blot and
      electron microscopy. Replication of the newly generated recombinant virus was
      comparable to parental NDV in embryonated chicken eggs. Immunization with
      chNDVFHN PMV8H5 stimulated full protection against lethal HPAIV infection in
      chickens without as well as with maternally derived NDV antibodies. Thus,
      tailored NDV vector vaccines can be provided for use in the presence or absence
      of routine NDV vaccination. 

PMID- 24023749
TI  - Four centuries of change in northeastern United States forests.
AB  - The northeastern United States is a predominately-forested region that, like most
      of the eastern U.S., has undergone a 400-year history of intense logging, land
      clearance for agriculture, and natural reforestation. This setting affords the
      opportunity to address a major ecological question: How similar are today's
      forests to those existing prior to European colonization? Working throughout a
      nine-state region spanning Maine to Pennsylvania, we assembled a comprehensive
      database of archival land-survey records describing the forests at the time of
      European colonization. We compared these records to modern forest inventory data
      and described: (1) the magnitude and attributes of forest compositional change,
      (2) the geography of change, and (3) the relationships between change and
      environmental factors and historical land use. We found that with few exceptions,
      notably the American chestnut, the same taxa that made up the pre-colonial forest
      still comprise the forest today, despite ample opportunities for species invasion
      and loss. Nonetheless, there have been dramatic shifts in the relative abundance
      of forest taxa. The magnitude of change is spatially clustered at local scales
      (<125 km) but exhibits little evidence of regional-scale gradients. Compositional
      change is most strongly associated with the historical extent of agricultural
      clearing. Throughout the region, there has been a broad ecological shift away
      from late successional taxa, such as beech and hemlock, in favor of early- and
      mid-successional taxa, such as red maple and poplar. Additionally, the modern
      forest composition is more homogeneous and less coupled to local climatic
      controls. 

PMID- 24023748
TI  - The effects of caffeine on sleep and maturational markers in the rat.
AB  - Adolescence is a critical period for brain maturation during which a massive
      reorganization of cortical connectivity takes place. In humans, slow wave
      activity (<4.5 Hz) during NREM sleep was proposed to reflect cortical maturation
      which relies on use-dependent processes. A stimulant like caffeine, whose
      consumption has recently increased especially in adolescents, is known to affect
      sleep wake regulation. The goal of this study was to establish a rat model
      allowing to assess the relationship between cortical maturation and sleep and to
      further investigate how these parameters are affected by caffeine consumption. To
      do so, we assessed sleep and markers of maturation by electrophysiological
      recordings, behavioral and structural readouts in the juvenile rat. Our results
      show that sleep slow wave activity follows a similar inverted U-shape trajectory
      as already known in humans. Caffeine treatment exerted short-term stimulating
      effects and altered the trajectory of slow wave activity. Moreover, caffeine
      affected behavioral and structural markers of maturation. Thus, caffeine
      consumption during a critical developmental period shows long lasting effects on
      sleep and brain maturation. 

PMID- 24023750
TI  - Development of transgenic cotton lines expressing Allium sativum agglutinin
      (ASAL) for enhanced resistance against major sap-sucking pests.
AB  - Mannose-specific Allium sativum leaf agglutinin encoding gene (ASAL) and
      herbicide tolerance gene (BAR) were introduced into an elite cotton inbred line
      (NC-601) employing Agrobacterium-mediated genetic transformation. Cotton
      transformants were produced from the phosphinothricin (PPT)-resistant shoots
      obtained after co-cultivation of mature embryos with the Agrobacterium strain
      EHA105 harbouring recombinant binary vector pCAMBIA3300-ASAL-BAR. PCR and
      Southern blot analysis confirmed the presence and stable integration of ASAL and
      BAR genes in various transformants of cotton. Basta leaf-dip assay, northern
      blot, western blot and ELISA analyses disclosed variable expression of BAR and
      ASAL transgenes in different transformants. Transgenes, ASAL and BAR, were stably
      inherited and showed co-segregation in T1 generation in a Mendelian fashion for
      both PPT tolerance and insect resistance. In planta insect bioassays on T2 and T3
      homozygous ASAL-transgenic lines revealed potent entomotoxic effects of ASAL on
      jassid and whitefly insects, as evidenced by significant decreases in the
      survival, development and fecundity of the insects when compared to the
      untransformed controls. Furthermore, the transgenic cotton lines conferred higher
      levels of resistance (1-2 score) with minimal plant damage against these major
      sucking pests when bioassays were carried out employing standard screening
      techniques. The developed transgenics could serve as a potential genetic resource
      in recombination breeding aimed at improving the pest resistance of cotton. This
      study represents the first report of its kind dealing with the development of
      transgenic cotton resistant to two major sap-sucking insects. 

PMID- 24023751
TI  - Positive effects of bacterial diversity on ecosystem functioning driven by
      complementarity effects in a bioremediation context.
AB  - Despite their importance as ecosystem drivers, our understanding of the influence
      of bacterial diversity on ecosystem functioning is limited. After identifying
      twelve bacterial strains from two petroleum-contaminated sites, we experimentally
      explored the impact of biodiversity on total density by manipulating the number
      of strains in culture. Irrespective of the origin of the bacteria relative to the
      contaminant, biodiversity positively influenced total density. However, bacteria
      cultured in the crude oil of their origin (autochthonous) reached higher
      densities than bacteria from another origin (allochthonous) and the relationship
      between diversity and density was stronger for autochthonous bacteria. By
      measuring the relative contribution of each strain to total density we showed
      that the observed positive effect of increasing diversity on total density was
      mainly due to positive interactions among species and not the presence of a
      particular species. Our findings can be explained by the complex chemical
      composition of crude oil and the necessity of a diverse array of organisms with
      complementary enzymatic capacities to achieve its degradation. The long term
      exposure to a contaminant may have allowed different bacteria to become adapted
      to the use of different fractions of the crude, resulting in higher
      complementarity in resource use in autochthonous bacteria compared to
      allochthonous ones. Our results could help improve the success of bioaugmentation
      as a bioremediation technique by suggesting the use of a diversified set of
      autochthonous organisms. 

PMID- 24023752
TI  - Concurrent outbreaks of cholera and peripheral neuropathy associated with high
      mortality among persons internally displaced by a volcanic eruption.
AB  - BACKGROUND: In October 2004, Manam Island volcano in Papua New Guinea erupted,
      causing over 10 000 villagers to flee to internally displaced person (IDP) camps,
      including 550 from Dugulaba village. Following violence over land access in March
      2010, the IDPs fled the camps, and four months later concurrent outbreaks of
      acute watery diarrhea and unusual neurological complaints were reported in this
      population. MATERIALS AND METHODS: A retrospective case-control study was
      conducted to identify the risk factors for peripheral neuropathy. Rectal swabs
      were collected from cases of acute watery diarrhea. Hair and serum metals and
      metalloids were analyzed by Inductively Coupled Plasma-Mass Spectrometry (ICP
      MS). RESULTS: There were 17 deaths among the 550 village inhabitants during the
      outbreak period at a crude mortality rate 21-fold that of a humanitarian crisis.
      Vibrio cholerae O1 El Tor Ogawa was confirmed among the population. Access to
      community-level rehydration was crucial to mortality. Peripheral neuropathy was
      diagnosed among cases with neurological symptoms. A balanced diet was
      significantly protective against neuropathy. A dose-response relationship was
      seen between peripheral neuropathy and a decreasing number of micronutrient- rich
      foods in the diet. Deficiencies in copper, iron, selenium and zinc were
      identified among the cases of peripheral neuropathy. CONCLUSIONS: Cholera likely
      caused the mostly preventable excess mortality. Peripheral neuropathy was not
      caused by cholera, but cholera may worsen existing nutritional deficiencies. The
      peripheral neuropathy was likely caused by complex micronutrient deficiencies
      linked to non-diversified diets that potentially increased the vulnerability of
      this population, however a new zinc-associated neuropathy could not be ruled out.
      Reoccurrence can be prevented by addressing the root cause of displacement and
      ensuring access to arable land and timely resettlement.

PMID- 24023753
TI  - Rehydration capacities and rates for various porcine tissues after dehydration.
AB  - The biphasic effects of liquid on tissue biomechanics are well known in cartilage
      and vocal folds, yet not extensively in other tissue types. Past studies have
      shown that tissue dehydration significantly impacts biomechanical properties and
      that rehydration can restore these properties in certain tissue types. However,
      these studies failed to consider how temporal exposure to dehydrating or
      rehydrating agents may alter tissue rehydration capacity, as overexposure to
      dehydration may permanently prevent rehydration to the initial liquid volume.
      Select porcine tissues were dehydrated until they reached between 100% and 40% of
      their initial mass. Each sample was allowed to rehydrate for 5 hours in a 0.9%
      saline solution, and the percent change between the initial and rehydrated mass
      values was calculated. Spearman correlation tests indicated a greater loss in
      mass despite rehydration when tissues were previously exposed to greater levels
      of dehydration. Additionally, Pearson correlation tests indicated the total
      liquid mass of samples after complete rehydration decreased when previously
      exposed to higher levels of dehydration. Rehydration rates were found by
      dehydrating tissues to 40% of their initial mass followed by rehydration in a
      0.9% saline solution for 60 minutes, with mass measurements occurring in 15
      minute intervals. All tissues rehydrated nonlinearly, most increasing
      significantly in mass up to 30 minutes after initial soaking. This study suggests
      the ability for tissues to rehydrate is dependent on the level of initial
      dehydration exposure. In vitro rehydration experiments therefore require
      controlled dosage and temporal exposure to dehydrating and rehydrating agents to
      avoid incomplete rehydration, and caution should be taken when combining
      different tissue types in models of hydration. 

PMID- 24023754
TI  - Comparative gene expression profiling identifies common molecular signatures of
      NF-kappaB activation in canine and human diffuse large B cell lymphoma (DLBCL).
AB  - We present the first comparison of global transcriptional changes in canine and
      human diffuse large B-cell lymphoma (DLBCL), with particular reference to the
      nuclear factor-kappa B (NF-kappaB) pathway. Microarray data generated from canine
      DLBCL and normal lymph nodes were used for differential expression, co-expression
      and pathway analyses, and compared with analysis of microarray data from human
      healthy and DLBCL lymph nodes. The comparisons at gene level were performed by
      mapping the probesets in canine microarrays to orthologous genes in humans and
      vice versa. A considerable number of differentially expressed genes between
      canine lymphoma and healthy lymph node samples were also found differentially
      expressed between human DLBCL and healthy lymph node samples. Principal component
      analysis using a literature-derived NF-kappaB target gene set mapped to
      orthologous canine array probesets and human array probesets clearly separated
      the healthy and cancer samples in both datasets. The analysis demonstrated that
      for both human and canine DLBCL there is activation of the NF-kappaB/p65
      canonical pathway, indicating that canine lymphoma could be used as a model to
      study NF-kappaB-targeted therapeutics for human lymphoma. To validate this,
      tissue arrays were generated for canine and human NHL and immunohistochemistry
      was employed to assess NF-kappaB activation status. In addition, human and canine
      B-cell lymphoma lines were assessed for NF-kappaB activity and the effects of NF
      kappaB inhibition. 

PMID- 24023756
TI  - A mouse variable gene fragment binds to DNA independently of the BCR context: a
      possible role for immature B-cell repertoire establishment.
AB  - B-cell maturation occurs in several steps and requires constant stimulus for its
      continuing development. From the emergence of the pre-B-cell receptor, signal
      transduction stimulates and supports B-cell development. Current viewpoints
      indicate that both positive selection pressure for autoantigens and tonic
      signaling constitutively stimulate B-cell maturation. In this work, we tested for
      the presence of a putative DNA binding site in a variable gene segment in a
      germline configuration, independently of VDJ recombination. After a survey of the
      public antibody databases, we chose a single mouse heavy variable gene segment
      that is highly represented in anti-nucleic acid antibodies and tested it for
      ssDNA binding. A phage display approach was used to search for intrinsic binding
      to oligo deoxythymidine. The results revealed that binding to an antigen can be
      influenced by the use of a specific DNA binding V[Formula: see text] gene
      segment. Our data support the idea that some variable genes have intrinsic
      reactivity towards specific types of endogenous autoantigens, and this property
      may contribute to the establishment of the immature B-cell repertoire. 

PMID- 24023755
TI  - Organelle and cellular abnormalities associated with hippocampal heterotopia in
      neonatal doublecortin knockout mice.
AB  - Heterotopic or aberrantly positioned cortical neurons are associated with
      epilepsy and intellectual disability. Various mouse models exist with forms of
      heterotopia, but the composition and state of cells developing in heterotopic
      bands has been little studied. Dcx knockout (KO) mice show hippocampal CA3
      pyramidal cell lamination abnormalities, appearing from the age of E17.5, and
      mice suffer from spontaneous epilepsy. The Dcx KO CA3 region is organized in two
      distinct pyramidal cell layers, resembling a heterotopic situation, and exhibits
      hyperexcitability. Here, we characterized the abnormally organized cells in
      postnatal mouse brains. Electron microscopy confirmed that the Dcx KO CA3 layers
      at postnatal day (P) 0 are distinct and separated by an intermediate layer devoid
      of neuronal somata. We found that organization and cytoplasm content of pyramidal
      neurons in each layer were altered compared to wild type (WT) cells. Less regular
      nuclei and differences in mitochondria and Golgi apparatuses were identified.
      Each Dcx KO CA3 layer at P0 contained pyramidal neurons but also other closely
      apposed cells, displaying different morphologies. Quantitative PCR and
      immunodetections revealed increased numbers of oligodendrocyte precursor cells
      (OPCs) and interneurons in close proximity to Dcx KO pyramidal cells.
      Immunohistochemistry experiments also showed that caspase-3 dependent cell death
      was increased in the CA1 and CA3 regions of Dcx KO hippocampi at P2. Thus,
      unsuspected ultrastructural abnormalities and cellular heterogeneity may lead to
      abnormal neuronal function and survival in this model, which together may
      contribute to the development of hyperexcitability. 

PMID- 24023757
TI  - Long-term effects of statin treatment in elderly people: extended follow-up of
      the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).
AB  - BACKGROUND: The PROspective Study of Pravastatin in the Elderly at Risk
      (PROSPER), a placebo-controlled trial of pravastatin, demonstrated a 19%
      reduction in coronary outcomes (p=0.006) after a mean of 3.2 years, with no
      impact on stroke outcomes or all-cause mortality. However, there was a suggestion
      of increased cancer risk. Our aim is to determine the long-term benefits and
      safety of pravastatin treatment in older people using post-trial follow-up of the
      PROSPER participants. METHODS: 5,804 (2,520 Scottish) men and women aged 70-82
      years with either pre-existing vascular disease or increased risk of such disease
      because of smoking, hypertension or diabetes, were randomised to 40 mg
      pravastatin or matching placebo. Using record linkage to routinely collected
      health records, all participants (full cohort) were linked to death and cancer
      registries, and the Scottish cohort additionally to hospital admissions, to
      provide composite fatal/non-fatal cardiovascular outcomes (total mean follow-up
      8.6 years). RESULTS: Pravastatin treatment for 3.2 years reduced CHD death in the
      full cohort, hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.68-0.95,
      p=0.0091 and fatal coronary events or coronary hospitalisations in the Scottish
      cohort (HR 0.81, 95% CI 0.69-0.95, p=0.0081) over 8.6 years. There was no
      reduction in stroke or all-cause mortality. Cancer risk was not increased in the
      full cohort (HR 1.08, 95% CI 0.96-1.21, p=0.22). CONCLUSIONS: Pravastatin
      treatment of elderly high-risk subjects for 3.2 years provided long-term
      protection against CHD events and CHD mortality. However, this was not associated
      with any increase in life expectancy, possibly due to competing mortality with
      deaths from other causes. There was no evidence of long-term increased risk of
      cancer. TRIAL REGISTRATION: ISRCTN40976937.

PMID- 24023758
TI  - Lack of association of apolipoprotein E (Apo E) epsilon2/epsilon3/epsilon4
      polymorphisms with primary open-angle glaucoma: a meta-analysis from 1916 cases
      and 1756 controls.
AB  - BACKGROUND: A number of case-control studies were conducted to investigate the
      association of apolipoprotein E (Apo E) polymorphisms with primary open angle
      glaucoma (POAG). But the results remain controversial. This meta-analysis aims to
      comprehensively evaluate the relationship between a common
      epsilon2/epsilon3/epsilon4 polymorphism in Apo E gene on the risk of POAG.
      METHOD: A comprehensive literature search for studies published up to April 2013
      was performed. Summary odds ratios (ORs) and 95% confidence intervals (CI) were
      calculated employing random-effects models irrespective of between-study
      heterogeneity. Publication bias of literatures was evaluated using funnel plots
      and Egger's test. RESULTS: A total of 12 studies including 1916 cases and 1756
      controls meeting the predefined criteria were involved in this meta-analysis.
      Overall, the Apo E epsilon2 allele and epsilon4 allele were not associated with
      POAG, compared with those carrying epsilon3 allele, with ORs of 0.98 (95% CI,
      0.79 to 1.23; P=0.872) and 1.05 (95% CI, 0.78 to 1.41; P=0.743), respectively.
      Genotypic analysis also found no significant association between the epsilon4
      carriers (epsilon3/epsilon4+epsilon4/epsilon4), epsilon2 carriers
      (epsilon2/epsilon3+epsilon2/epsilon2) and POAG, compared with participants with
      Apo E epsilon3/3, with ORs of 0.91 (95% CI, 0.66 to 1.25; P=0.543) and 1.08 (95%
      CI, 0.74 to 1.57; P=0.694), respectively. In the subgroup analysis by ethnicity,
      source of controls, genotyping methods, Hardy-Weinberg equilibrium or not, or
      type of the POAG, still no obvious associations were found. CONCLUSIONS: This
      meta-analysis suggests that Apo E epsilon2/epsilon3/epsilon4 polymorphisms may
      not be associated with the risk of POAG. However, well-designed studies with
      larger sample size and more ethnic groups are required to further validate the
      results.

PMID- 24023759
TI  - Whole genome mapping and re-organization of the nuclear and mitochondrial genomes
      of Babesia microti isolates.
AB  - Babesia microti is the primary causative agent of human babesiosis, an emerging
      pathogen that causes a malaria-like illness with possible fatal outcome in
      immunocompromised patients. The genome sequence of the B. microti R1 strain was
      reported in 2012 and revealed a distinct evolutionary path for this pathogen
      relative to that of other apicomplexa. Lacking from the first genome assembly and
      initial molecular analyses was information about the terminal ends of each
      chromosome, and both the exact number of chromosomes in the nuclear genome and
      the organization of the mitochondrial genome remained ambiguous. We have now
      performed various molecular analyses to characterize the nuclear and
      mitochondrial genomes of the B. microti R1 and Gray strains and generated high
      resolution Whole Genome maps. These analyses show that the genome of B. microti
      consists of four nuclear chromosomes and a linear mitochondrial genome present in
      four different structural types. Furthermore, Whole Genome mapping allowed
      resolution of the chromosomal ends, identification of areas of misassembly in the
      R1 genome, and genomic differences between the R1 and Gray strains, which occur
      primarily in the telomeric regions. These studies set the stage for a better
      understanding of the evolution and diversity of this important human pathogen. 

PMID- 24023760
TI  - Life history plasticity of a tropical seabird in response to El Nino anomalies
      during early life.
AB  - Food shortage and other challenges associated with El Nino Southern Oscillation
      (ENSO) experienced early in life may have long-term impacts on life history
      traits, but these potential impacts remain virtually unexplored. By monitoring
      2556 blue-footed boobies from 11 cohorts, we showed that birds facing warm water
      ENSO conditions (and probably low food availability) in the natal year were
      underweight at fledging, recruited earlier and bred less frequently, but showed
      no deficit in longevity or breeding success over the first 10 years. Life history
      impacts of ENSO were substantial when experienced in the prenatal year, the natal
      year, or the second year of life, and absent when experienced in the third year
      of life, implying that harsh conditions have greater effects when experienced
      earlier in life. Sexual differences in impacts depended on the age when warm
      water conditions were experienced: pre-natal and natal experience, respectively,
      induced early recruitment and influenced the relationship between age and laying
      date only in females, whereas second year experience reduced total breeding
      success only of males. Most surprising were positive transgenerational impacts in
      females: daughters of females that experienced ENSO conditions in their natal
      year showed improved breeding success. Developmental plasticity of boobies thus
      enables them to largely neutralize potential long-term impacts of harsh climatic
      conditions experienced early in life. 

PMID- 24023761
TI  - Profiling the dynamics of a human phosphorylome reveals new components in HGF/c
      Met signaling.
AB  - Protein phosphorylation is a dynamic and reversible event that greatly influences
      cellular function. Identifying the key regulatory elements that determine
      cellular phenotypes during development and oncogenesis requires the ability to
      dynamically monitor proteome-wide events. Here, we report the development of a
      new strategy to monitor dynamic changes of protein phosphorylation in cells and
      tissues using functional protein microarrays as the readout. To demonstrate this
      technology's ability to identify condition-dependent phosphorylation events,
      human protein microarrays were incubated with lysates from cells or tissues under
      activation or inhibition of c-Met, a receptor tyrosine kinase involved in tissue
      morphogenesis and malignancy. By comparing the differences between the protein
      phosphorylation profiles obtained using the protein microarrays, we were able to
      recover many of the proteins that are known to be specifically activated (i.e.,
      phosphorylated) upon c-Met activation by the hepatocyte growth factor (HGF). Most
      importantly, we discovered many proteins that were differentially phosphorylated
      by lysates from cells or tissues when the c-Met pathway was active. Using
      phosphorylation-specific antibodies, we were able to validate several candidate
      proteins as new downstream components of the c-Met signaling pathway in cells. We
      envision that this new approach, like its DNA microarray counterpart, can be
      further extended toward profiling dynamics of global protein phosphorylation
      under many different physiological conditions both in cellulo and in vivo in a
      high-throughput and cost-effective fashion. 

PMID- 24023762
TI  - Homoarginine and mortality in pre-dialysis chronic kidney disease (CKD) patients.
AB  - BACKGROUND AND AIMS: Homoarginine, a precursor of nitric oxide, is an inverse
      predictor of death in dialysis patients and in subjects with cardiovascular
      disease and normal kidney function but its relationship with clinical outcomes in
      chronic kidney disease (CKD) patients not yet on dialysis is unknown. DESIGN
      SETTING PARTICIPANTS AND MEASUREMENTS: We enrolled 168 consecutive predialysis
      CKD patients (Age: 70 +/- 11 yrs; 26% Diabetics; eGFR 34 +/- 18 ml/min/1.73 m(2))
      referred to a tertiary care centre and measured laboratory data on kidney
      function and cardiovascular risk factors. We modeled progression to dialysis or
      death as a function of homoarginine, using Cox's regression, accounting for
      clinical characteristics, baseline levels of kidney function, and markers of
      inflammation. RESULTS: On crude and adjusted analyses homoarginine was directly
      associated with the eGFR and patients with more compromised renal function
      exhibited lower homoarginine levels. Furthermore homoarginine was also
      independently related to L-arginine, serum albumin and body mass index, and
      inversely related to proteinuria, C-reactive protein and age. During the study
      (follow up median time 4 years, inter-quartile range 1.7 to 7.0 years) 56
      patients started dialysis and 103 died and homoarginine was a strong inverse
      predictor of the incidence rate of both outcomes (P=0.002 and P=0.017).
      CONCLUSIONS: Homoarginine declines with advancing renal disease and is inversely
      related to progression to dialysis and mortality. The nature of the link between
      homoarginine and clinical outcomes is amenable to testing in clinical trials.

PMID- 24023763
TI  - Effect of different suprahepatic vena cava reconstruction methods on the
      hemodynamics of rats after liver transplantation.
AB  - BACKGROUND: There are few studies on the hemodynamic changes after orthotopic
      liver transplantation in rats. In this study, we aimed to evaluate the effect of
      different suprahepatic vena cava (SHVC) reconstruction methods on the
      hemodynamics of rats after liver transplantation. MATERIALS AND METHODS: Three
      rat liver transplantation groups were created according to the SHVC
      reconstruction method: Kamada's two-cuff technique, a modified veno-lined stent
      technique, and Harihara's three-cuff technique. Ten rats of similar weight were
      grouped as the control. Anatomical, ultrasonic, and hemodynamic parameters and
      the microcirculation of the liver were measured after transplantation. The
      detailed operation time, operative complications, and animal survival were
      recorded. RESULTS: All the recipients showed portal hypertension one month after
      transplantation. The portal hypertension in the group with the modified veno
      lined stent technique was the most severe. The value measured with real-time
      elastography was significantly higher in the recipients using the modified veno
      lined stent technique than in the other two groups (P<0.01). There was no
      difference in the graft microcirculation after reperfusion among the three
      groups. The survival rate of the three groups displayed no difference, but the
      modified veno-lined stent technique led to more venous complications than the
      other two techniques. CONCLUSIONS: The hemodynamics after liver transplantation
      in rats is determined not only by the cuff used for portal vein reconstruction
      but also by the cuff or stent for the SHVC. Some SHVC reconstruction methods,
      such as the modified veno-lined stent technique, Miyata's or Settaf's three-cuff
      techniques, significantly affect the hemodynamics.

PMID- 24023764
TI  - CT image sequence restoration based on sparse and low-rank decomposition.
AB  - Blurry organ boundaries and soft tissue structures present a major challenge in
      biomedical image restoration. In this paper, we propose a low-rank decomposition
      based method for computed tomography (CT) image sequence restoration, where the
      CT image sequence is decomposed into a sparse component and a low-rank component.
      A new point spread function of Weiner filter is employed to efficiently remove
      blur in the sparse component; a wiener filtering with the Gaussian PSF is used to
      recover the average image of the low-rank component. And then we get the
      recovered CT image sequence by combining the recovery low-rank image with all
      recovery sparse image sequence. Our method achieves restoration results with
      higher contrast, sharper organ boundaries and richer soft tissue structure
      information, compared with existing CT image restoration methods. The robustness
      of our method was assessed with numerical experiments using three different low
      rank models: Robust Principle Component Analysis (RPCA), Linearized Alternating
      Direction Method with Adaptive Penalty (LADMAP) and Go Decomposition (GoDec).
      Experimental results demonstrated that the RPCA model was the most suitable for
      the small noise CT images whereas the GoDec model was the best for the large
      noisy CT images. 

PMID- 24023765
TI  - In-depth characterization of microRNA transcriptome in melanoma.
AB  - The full repertoire of human microRNAs (miRNAs) that could distinguish common
      (benign) nevi from cutaneous (malignant) melanomas remains to be established. In
      an effort to gain further insight into the role of miRNAs in melanoma, we applied
      Illumina next-generation sequencing (NGS) platform to carry out an in-depth
      analysis of miRNA transcriptome in biopsies of nevi, thick primary (>4.0 mm) and
      metastatic melanomas with matched normal skin in parallel to melanocytes and
      melanoma cell lines (both primary and metastatic) (n=28). From this data
      representing 698 known miRNAs, we defined a set of top-40 list, which properly
      classified normal from cancer; also confirming 23 (58%) previously discovered
      miRNAs while introducing an additional 17 (42%) known and top-15 putative novel
      candidate miRNAs deregulated during melanoma progression. Surprisingly, the miRNA
      signature distinguishing specimens of melanoma from nevus was significantly
      different than that of melanoma cell lines from melanocytes. Among the top list,
      miR-203, miR-204-5p, miR-205-5p, miR-211-5p, miR-23b-3p, miR-26a-5p and miR-26b
      5p were decreased in melanomas vs. nevi. In a validation cohort (n=101), we
      verified the NGS results by qRT-PCR and showed that receiver-operating
      characteristic curves for miR-211-5p expression accurately discriminated invasive
      melanoma (AUC=0.933), melanoma in situ (AUC=0.933) and dysplastic (atypical) nevi
      (AUC=0.951) from common nevi. Target prediction analysis of co-transcribed miRNAs
      showed a cooperative regulation of key elements in the MAPK signaling pathway.
      Furthermore, we found extensive sequence variations (isomiRs) and other non
      coding small RNAs revealing a complex melanoma transcriptome. Deep-sequencing
      small RNAs directly from clinically defined specimens provides a robust strategy
      to improve melanoma diagnostics.

PMID- 24023766
TI  - Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta
      analysis and systematic review.
AB  - OBJECTIVE: Osteoarthritis (OA) is the most common form of arthritis worldwide.
      Pain and reduced function are the main symptoms in this prevalent disease. There
      are currently no treatments for OA that modify disease progression; therefore
      analgesic drugs and joint replacement for larger joints are the standard of care.
      In light of several recent studies reporting the use of bisphosphonates for OA
      treatment, our work aimed to evaluate published literature to assess the
      effectiveness of bisphosphonates in OA treatment. METHODS: Literature databases
      were searched from inception to the 30th June 2012 for clinical trials of
      bisphosphonates to treat OA pain. Data was appraised and levels of evidence
      determined qualitatively using best evidence synthesis from the Cochrane
      Collaboration. The two largest studies were conducted with risedronate in the
      treatment of knee OA, for which meta-analyses were performed for pain and
      functional outcomes. RESULTS: Our searches found 13/297 eligible studies, which
      included a total of 3832 participants. The trials recruited participants with OA
      of the hand (n=1), knee (n=8), knee and spine (n=3), or hip (n=1). Our meta
      analysis of the two largest knee studies using risedronate 15 mg showed odds
      ratios favouring placebo interventions for the Western Ontario and McMaster
      Universities Arthritis Index (WOMAC) pain (1.73), WOMAC function (2.03), and
      WOMAC stiffness (1.82). However, 8 trials (61.5%) reported that bisphosphonates
      improve pain assessed by VAS scores and 2 (38.5%) reported significant
      improvement in WOMAC pain scores compared to control groups. CONCLUSIONS: There
      is limited evidence that bisphosphonates are effective in the treatment of OA
      pain. Limitations of the studies we analysed included the differences in duration
      of bisphosphonate use, the dose and route of administration and the lack of long
      term data on OA joint structure modification post-bisphosphonate therapy. Future
      more targeted studies are required to appreciate the value of bisphosphonates in
      treating osteoarthritis pain. TRIAL REGISTRATION: PROSPERO Register
      CRD42012002541.

PMID- 24023767
TI  - Consumption of dairy products and colorectal cancer in the European Prospective
      Investigation into Cancer and Nutrition (EPIC).
AB  - BACKGROUND: Prospective studies have consistently reported lower colorectal
      cancer risks associated with higher intakes of total dairy products, total milk
      and dietary calcium. However, less is known about whether the inverse
      associations vary for individual dairy products with differing fat contents.
      MATERIALS AND METHODS: In the European Prospective Investigation into Cancer and
      Nutrition (EPIC), we investigated the associations between intakes of total milk
      and milk subtypes (whole-fat, semi-skimmed and skimmed), yoghurt, cheese, and
      dietary calcium with colorectal cancer risk amongst 477,122 men and women.
      Dietary questionnaires were administered at baseline. Multivariable hazard ratios
      (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional
      hazards models, adjusted for relevant confounding variables. RESULTS: During the
      mean 11 years of follow-up, 4,513 incident cases of colorectal cancer occurred.
      After multivariable adjustments, total milk consumption was inversely associated
      with colorectal cancer risk (HR per 200 g/day 0.93, 95% CI: 0.89-0.98). Similar
      inverse associations were observed for whole-fat (HR per 200 g/day 0.90, 95% CI:
      0.82-0.99) and skimmed milk (HR per 200 g/day 0.90, 95% CI: 0.79-1.02) in the
      multivariable models. Inverse associations were observed for cheese and yoghurt
      in the categorical models; although in the linear models, these associations were
      non-significant. Dietary calcium was inversely associated with colorectal cancer
      risk (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99); this association was limited to
      dairy sources of calcium only (HR per 200 mg/day 0.95, 95% CI: 0.91-0.99), with
      no association observed for non-dairy calcium sources (HR per 200 mg/day 1.00,
      95% CI: 0.81-1.24). CONCLUSIONS: Our results strengthen the evidence for a
      possible protective role of dairy products on colorectal cancer risk. The inverse
      associations we observed did not differ by the fat content of the dairy products
      considered.

PMID- 24023768
TI  - Molecular basis of renal adaptation in a murine model of congenital obstructive
      nephropathy.
AB  - Congenital obstructive nephropathy is a common cause of chronic kidney disease
      and a leading indication for renal transplant in children. The cellular and
      molecular responses of the kidney to congenital obstruction are incompletely
      characterized. In this study, we evaluated global transcription in kidneys with
      graded hydronephrosis in the megabladder (mgb (-/-)) mouse to better understand
      the pathophysiology of congenital obstructive nephropathy. Three primary pathways
      associated with kidney remodeling/repair were induced in mgb (-/-) kidneys
      independent of the degree of hydronephrosis. These pathways included retinoid
      signaling, steroid hormone metabolism, and renal response to injury. Urothelial
      proliferation and the expression of genes with roles in the integrity and
      maintenance of the renal urothelium were selectively increased in mgb (-/-)
      kidneys. Ngal/Lcn2, a marker of acute kidney injury, was elevated in 36% of
      kidneys with higher grades of hydronephrosis. Evaluation of Ngal(high) versus
      Ngal(low) kidneys identified the expression of several novel candidate markers of
      renal injury. This study indicates that the development of progressive
      hydronephrosis in mgb (-/-) mice results in renal adaptation that includes
      significant changes in the morphology and potential functionality of the renal
      urothelium. These observations will permit the development of novel biomarkers
      and therapeutic approaches to progressive renal injury in the context of
      congenital obstruction. 

PMID- 24023769
TI  - Dual role of phi29 DNA polymerase Lys529 in stabilisation of the DNA priming
      terminus and the terminal protein-priming residue at the polymerisation site.
AB  - Resolution of the crystallographic structure of phi29 DNA polymerase binary and
      ternary complexes showed that residue Lys529, located at the C-terminus of the
      palm subdomain, establishes contacts with the 3' terminal phosphodiester bond. In
      this paper, site-directed mutants at this Lys residue were used to analyse its
      functional importance for the synthetic activities of phi29 DNA polymerase, an
      enzyme that starts linear phi29 DNA replication using a terminal protein (TP) as
      primer. Our results show that single replacement of phi29 DNA polymerase residue
      Lys529 by Ala or Glu decreases the stabilisation of the primer-terminus at the
      polymerisation active site, impairing both the insertion of the incoming
      nucleotide when DNA and TP are used as primers and the translocation step
      required for the next incoming nucleotide incorporation. In addition, combination
      of the DNA polymerase mutants with a TP derivative at residue Glu233, neighbour
      to the priming residue Ser232, leads us to infer a direct contact between Lys529
      and Glu233 for initiation of TP-DNA replication. Altogether, the results are
      compatible with a sequential binding of phi29 DNA polymerase residue Lys529 with
      TP and DNA during replication of TP-DNA. 

PMID- 24023770
TI  - Biogeography of Deep-sea benthic bacteria at regional scale (LTER HAUSGARTEN,
      Fram Strait, Arctic).
AB  - Knowledge on spatial scales of the distribution of deep-sea life is still sparse,
      but highly relevant to the understanding of dispersal, habitat ranges and
      ecological processes. We examined regional spatial distribution patterns of the
      benthic bacterial community and covarying environmental parameters such as water
      depth, biomass and energy availability at the Arctic Long-Term Ecological
      Research (LTER) site HAUSGARTEN (Eastern Fram Strait). Samples from 13 stations
      were retrieved from a bathymetric (1,284-3,535 m water depth, 54 km in length)
      and a latitudinal transect (~ 2,500 m water depth; 123 km in length). 454
      massively parallel tag sequencing (MPTS) and automated ribosomal intergenic
      spacer analysis (ARISA) were combined to describe both abundant and rare types
      shaping the bacterial community. This spatial sampling scheme allowed detection
      of up to 99% of the estimated richness on phylum and class levels. At the
      resolution of operational taxonomic units (97% sequence identity; OTU3%) only 36%
      of the Chao1 estimated richness was recovered, indicating a high diversity,
      mostly due to rare types (62% of all OTU3%). Accordingly, a high turnover of the
      bacterial community was also observed between any two sampling stations (average
      replacement of 79% of OTU3%), yet no direct correlation with spatial distance was
      observed within the region. Bacterial community composition and structure
      differed significantly with increasing water depth along the bathymetric
      transect. The relative sequence abundance of Verrucomicrobia and Planctomycetes
      decreased significantly with water depth, and that of Deferribacteres increased.
      Energy availability, estimated from phytodetrital pigment concentrations in the
      sediments, partly explained the variation in community structure. Overall, this
      study indicates a high proportion of unique bacterial types on relatively small
      spatial scales (tens of kilometers), and supports the sampling design of the LTER
      site HAUSGARTEN to study bacterial community shifts in this rapidly changing area
      of the world's oceans. 

PMID- 24023771
TI  - Involvement of the G-protein-coupled dopamine/ecdysteroid receptor DopEcR in the
      behavioral response to sex pheromone in an insect.
AB  - Most animals including insects rely on olfaction to find their mating partners.
      In moths, males are attracted by female-produced sex pheromones inducing
      stereotyped sexual behavior. The behaviorally relevant olfactory information is
      processed in the primary olfactory centre, the antennal lobe (AL). Evidence is
      now accumulating that modulation of sex-linked behavioral output occurs through
      neuronal plasticity via the action of hormones and/or catecholamines. A G-protein
      coupled receptor (GPCR) binding to 20-hydroxyecdysone, the main insect steroid
      hormone, and dopamine, has been identified in Drosophila (DmDopEcR), and was
      suggested to modulate neuronal signaling. In the male moth Agrotis ipsilon, the
      behavioral and central nervous responses to pheromone are age-dependent. To
      further unveil the mechanisms of this olfactory plasticity, we searched for
      DopEcR and tested its potential role in the behavioral response to sex pheromone
      in A. ipsilon males. Our results show that A. ipsilon DopEcR (named AipsDopEcR)
      is predominantly expressed in the nervous system. The corresponding protein was
      detected immunohistochemically in the ALs and higher brain centers including the
      mushroom bodies. Moreover, AipsDopEcR expression increased with age. Using a
      strategy of RNA interference, we also show that silencing of AipsDopEcR inhibited
      the behavioral response to sex pheromone in wind tunnel experiments. Altogether
      our results indicate that this GPCR is involved in the expression of sexual
      behavior in the male moth, probably by modulating the central nervous processing
      of sex pheromone through the action of one or both of its ligands. 

PMID- 24023773
TI  - Global causes of diarrheal disease mortality in children <5 years of age: a
      systematic review.
AB  - Estimation of pathogen-specific causes of child diarrhea deaths is needed to
      guide vaccine development and other prevention strategies. We did a systematic
      review of articles published between 1990 and 2011 reporting at least one of 13
      pathogens in children <5 years of age hospitalized with diarrhea. We included
      2011 rotavirus data from the Rotavirus Surveillance Network coordinated by WHO.
      We excluded studies conducted during diarrhea outbreaks that did not discriminate
      between inpatient and outpatient cases, reporting nosocomial infections, those
      conducted in special populations, not done with adequate methods, and rotavirus
      studies in countries where the rotavirus vaccine was used. Age-adjusted median
      proportions for each pathogen were calculated and applied to 712 000 deaths due
      to diarrhea in children under 5 years for 2011, assuming that those observed
      among children hospitalized for diarrhea represent those causing child diarrhea
      deaths. 163 articles and WHO studies done in 31 countries were selected
      representing 286 inpatient studies. Studies seeking only one pathogen found
      higher proportions for some pathogens than studies seeking multiple pathogens
      (e.g. 39% rotavirus in 180 single-pathogen studies vs. 20% in 24 studies with 5
      13 pathogens, p<0.0001). The percentage of episodes for which no pathogen could
      be identified was estimated to be 34%; the total of all age-adjusted percentages
      for pathogens and no-pathogen cases was 138%. Adjusting all proportions,
      including unknowns, to add to 100%, we estimated that rotavirus caused 197 000
      [Uncertainty range (UR) 110 000-295 000], enteropathogenic E. coli 79 000 (UR 31
      000-146 000), calicivirus 71 000 (UR 39 000-113 000), and enterotoxigenic E. coli
      42 000 (UR 20 000-76 000) deaths. Rotavirus, calicivirus, enteropathogenic and
      enterotoxigenic E. coli cause more than half of all diarrheal deaths in children
      <5 years in the world.

PMID- 24023772
TI  - The viruses of wild pigeon droppings.
AB  - Birds are frequent sources of emerging human infectious diseases. Viral particles
      were enriched from the feces of 51 wild urban pigeons (Columba livia) from Hong
      Kong and Hungary, their nucleic acids randomly amplified and then sequenced. We
      identified sequences from known and novel species from the viral families
      Circoviridae, Parvoviridae, Picornaviridae, Reoviridae, Adenovirus, Astroviridae,
      and Caliciviridae (listed in decreasing number of reads), as well as plant and
      insect viruses likely originating from consumed food. The near full genome of a
      new species of a proposed parvovirus genus provisionally called Aviparvovirus
      contained an unusually long middle ORF showing weak similarity to an ORF of
      unknown function from a fowl adenovirus. Picornaviruses found in both Asia and
      Europe that are distantly related to the turkey megrivirus and contained a highly
      divergent 2A1 region were named mesiviruses. All eleven segments of a novel
      rotavirus subgroup related to a chicken rotavirus in group G were sequenced and
      phylogenetically analyzed. This study provides an initial assessment of the
      enteric virome in the droppings of pigeons, a feral urban species with frequent
      human contact. 

PMID- 24023774
TI  - Continuation of exercise is necessary to inhibit high fat diet-induced beta
      amyloid deposition and memory deficit in amyloid precursor protein transgenic
      mice.
AB  - High fat diet (HFD) is prevalent in many modern societies and HFD-induced
      metabolic condition is a growing concern worldwide. It has been previously
      reported that HFD clearly worsens cognitive function in amyloid precursor protein
      (APP) transgenic mice. On the other hand, we have demonstrated that voluntary
      exercise in an enriched environment is an effective intervention to rescue HFD
      induced beta-amyloid (Abeta) deposition and memory deficit. However, it had been
      unclear whether consumption of HFD after exercising abolished the beneficial
      effect of exercise on the inhibition of Alzheimer's disease (AD) pathology. To
      examine this question, we exposed wild type (WT) and APP mice fed with HFD to
      exercise conditions at different time periods. In our previous experiment, we
      gave HFD to mice for 20 weeks and subjected them to exercise during weeks 10-20.
      In the present study, mice were subjected to exercise conditions during weeks 0
      10 or weeks 5-15 while being on HFD. Interestingly, we found that the effect of
      exercise during weeks 0-10 or weeks 5-15 on memory function was not abolished in
      WT mice even if they kept having HFD after finishing exercise. However, in APP
      transgenic mice, HFD clearly disrupted the effect of exercise during weeks 0-10
      or weeks 5-15 on memory function. Importantly, we observed that the level of
      Abeta oligomer was significantly elevated in the APP mice that exercised during
      weeks 0-10: this might have been caused by the up-regulation of Abeta production.
      These results provide solid evidence that continuation of exercise is necessary
      to rescue HFD-induced aggravation of cognitive decline in the pathological
      setting of AD. 

PMID- 24023775
TI  - Association of interferon-gamma induced protein 10 promoter polymorphisms with
      the disease progression of hepatitis B virus infection in Chinese Han population.
AB  - BACKGROUND AND AIMS: Interferon-gamma induced protein 10 (IP-10) was suggested to
      be involved in liver injury in viral hepatitis. This study aimed to investigate
      the impact of the single nucleotide polymorphisms (SNP) G-201A (rs1439490) in IP
      10 gene on disease progression of hepatitis B virus (HBV) infection. METHODS: The
      -201 SNP in IP-10 promoter was genotyped from 577 patients with different illness
      categories and 275 health controls; In vitro IP-10 promoter activity was compared
      between haplotype GG and AA homozygotes using luciferase reporter system in HepG2
      cells. In vivo expression of IP-10 was compared between patients with -201 AA
      genotype and GG genotype. RESULTS: The detected frequency of G-201A SNP was
      17.8%, 25.3%, 26.6%, and 13.8% for patients with acute hepatitis B (AHB),
      patients with mild chronic hepatitis B (CHB-M), patients with severe chronic
      hepatitis B (CHB-S), and health controls, respectively. In vitro IP-10 promoter
      driven luciferase activity in pGL3-Enhancer-201A transfected HepG2 cells was 1.43
      fold higher than that in pGL3-Enhancer-201G transfected HepG2 cells (P<0.01). In
      vivo IP-10 transcriptional expression of peripheral blood mononuclear cells was
      1.38-fold higher in patients with -201 AA genotype than in patients with -201 GG
      genotype (P<0.01). CONCLUSION: G-201A in promoter region of IP-10 gene was
      associated with liver disease progression in patients with HBV infection through
      up-regulating IP-10 expression.

PMID- 24023776
TI  - Interleukin-21 accelerates thymic recovery from glucocorticoid-induced atrophy.
AB  - Both physiological and psychological stress cause thymic atrophy via
      glucocorticoid (GC)-dependent apoptosis of double-positive (DP) thymocytes. Given
      the pervasiveness of stress, GC-induced thymic atrophy is arguably the most
      common type of acquired immunodeficiency. We recently reported that interleukin
      21 (IL-21) has a unique ability to expand the small subset of DP thymocytes
      (CD69(+)) which are ongoing positive selection, and that administration of IL-21
      increases thymic output in aged mice. The goal of this study was to evaluate
      whether IL-21 could mitigate GC-induced thymic atrophy. In contrast to double
      negative (DN) and single-positive (SP) thymocytes, most DP thymocytes (CD69(-))
      do not constitutively express the IL-21 receptor (IL-21R). Accordingly, CD69(-)
      DP thymocytes from PBS-treated mice were unresponsive to IL-21 administration.
      However, following GC injection, surviving CD69(-) DP thymocytes up-regulated IL
      21R and responded to IL-21 treatment as evidenced by enhancement of Bcl6
      expression and phosphorylation of STAT1, STAT3 and STAT5. Consequently, IL-21
      administration to GC-treated mice accelerated thymic recovery by expanding
      considerably DP thymocytes and, to a lesser extent, DN thymocytes. However, IL-21
      induced expansion of DN/DP thymocytes did not alter the diversity of the
      intrathymic or peripheral T-cell receptor (TCR) repertoire. We conclude that IL
      21 dramatically accelerates recovery from GC-induced thymic atrophy. 

PMID- 24023777
TI  - Identification of a susceptibility locus for severe adolescent idiopathic
      scoliosis on chromosome 17q24.3.
AB  - Adolescent idiopathic scoliosis (AIS) is the most common spinal deformity,
      affecting around 2% of adolescents worldwide. Genetic factors play an important
      role in its etiology. Using a genome-wide association study (GWAS), we recently
      identified novel AIS susceptibility loci on chromosomes 10q24.31 and 6q24.1. To
      identify more AIS susceptibility loci relating to its severity and progression,
      we performed GWAS by limiting the case subjects to those with severe AIS. Through
      a two-stage association study using a total of ~12,000 Japanese subjects, we
      identified a common variant, rs12946942 that showed a significant association
      with severe AIS in the recessive model (P=4.00 * 10(-8), odds ratio [OR]=2.05).
      Its association was replicated in a Chinese population (combined P=6.43 * 10(
      12), OR = 2.21). rs12946942 is on chromosome 17q24.3 near the genes SOX9 and
      KCNJ2, which when mutated cause scoliosis phenotypes. Our findings will offer new
      insight into the etiology and progression of AIS.

PMID- 24023778
TI  - Effects of abscisic acid, gibberellin, ethylene and their interactions on
      production of phenolic acids in salvia miltiorrhiza bunge hairy roots.
AB  - Salvia miltiorrhiza is one of the most important traditional Chinese medicinal
      plants because of its excellent performance in treating coronary heart disease.
      Phenolic acids mainly including caffeic acid, rosmarinic acid and salvianolic
      acid B are a group of active ingredients in S. miltiorrhiza. Abscisic acid (ABA),
      gibberellin (GA) and ethylene are three important phytohormones. In this study,
      effects of the three phytohormones and their interactions on phenolic production
      in S. miltiorrhiza hairy roots were investigated. The results showed that ABA, GA
      and ethylene were all effective to induce production of phenolic acids and
      increase activities of PAL and TAT in S. miltiorrhiza hairy roots. Effects of
      phytohormones were reversed by their biosynthetic inhibitors. Antagonistic
      actions between the three phytohormones played important roles in the
      biosynthesis of phenolic acids. GA signaling is necessary for ABA and ethylene
      induced phenolic production. Yet, ABA and ethylene signaling is probably not
      necessary for GA3-induced phenolic production. The complex interactions of
      phytohormones help us reveal regulation mechanism of secondary metabolism and
      scale-up production of active ingredients in plants. 

PMID- 24023779
TI  - Role of the N-terminal seven residues of surfactant protein B (SP-B).
AB  - Breathing is enabled by lung surfactant, a mixture of proteins and lipids that
      forms a surface-active layer and reduces surface tension at the air-water
      interface in lungs. Surfactant protein B (SP-B) is an essential component of lung
      surfactant. In this study we probe the mechanism underlying the important
      functional contributions made by the N-terminal 7 residues of SP-B, a region
      sometimes called the "insertion sequence". These studies employed a construct of
      SP-B, SP-B (1-25,63-78), also called Super Mini-B, which is a 41-residue peptide
      with internal disulfide bonds comprising the N-terminal 7-residue insertion
      sequence and the N- and C-terminal helices of SP-B. Circular dichroism, solution
      NMR, and solid state (2)H NMR were used to study the structure of SP-B (1-25,63
      78) and its interactions with phospholipid bilayers. Comparison of results for SP
      B (8-25,63-78) and SP-B (1-25,63-78) demonstrates that the presence of the 7
      residue insertion sequence induces substantial disorder near the centre of the
      lipid bilayer, but without a major disruption of the overall mechanical
      orientation of the bilayers. This observation suggests the insertion sequence is
      unlikely to penetrate deeply into the bilayer. The 7-residue insertion sequence
      substantially increases the solution NMR linewidths, most likely due to an
      increase in global dynamics. 

PMID- 24023780
TI  - Predictors and consequences of global DNA methylation in cord blood and at three
      years.
AB  - DNA methylation changes have been implicated in many common chronic diseases
      leading to the hypothesis that environmental and age-related DNA methylation
      changes within individuals are involved in disease etiology. Few studies have
      examined DNA methylation changes within an individual over time and all of these
      studies have been conducted in adults. Here, we aim to characterize how global
      DNA methylation changes from birth to age three within a longitudinal birth
      cohort study and to determine whether there are consistent predictors of DNA
      methylation levels measured three years apart. We measured global DNA methylation
      in the same children at birth (cord blood) and again at three years of age among
      165 children, using an immunoassay. We found that on average, DNA methylation was
      significantly higher in blood at age 3-years than in cord blood (p<0.01).
      However, for any individual child, the difference was less than would be expected
      by chance. We found that pre-pregnancy BMI was negatively predictive of both cord
      and three-year DNA methylation, even after statistical adjustment to account for
      the correlation between cord blood and three-year DNA methylation. The biologic
      implications of small changes in global DNA methylation are unknown. However, the
      observation that global DNA methylation levels persist within an individual from
      birth to age three supports the belief that factors that influence global DNA
      methylation, including pre-pregnancy BMI, may confer long-term effects. 

PMID- 24023781
TI  - Dual dependence of cryobiogical properties of Sf21 cell membrane on the
      temperature and the concentration of the cryoprotectant.
AB  - The Sf21 cell line is extensively used for virus research and producing
      heterologous recombinant proteins. To develop optimal strategies for minimizing
      cell injury due to intracellular ice formation and excessive volume shrinkage
      during cryopreservation, the fundamental transport properties including the
      osmotic inactive volume (Vb ), the hydraulic conductivity (Lp ), and the glycerol
      permeability (Ps ) of Sf21 cell membrane at 25, 15, 5 and -2 degrees C were
      characterized using a micro-perfusion chamber. The effects of temperature on the
      hydraulic conductivity and the glycerol permeability of Sf21 cell membrane,
      reflected by the activation energies, were quantitatively investigated. It was
      found that the hydraulic conductivity decreases along with the increase of the
      final CPA concentration at a given temperature, and quantitative analysis
      indicates that the hydraulic conductivity has a significant linear attenuation
      along with the increase of the concentration of glycerol. Therefore, we
      incorporate the concentration dependence of the hydraulic conductivity into the
      classic Arrhenius relationship by replacing the constant reference value of the
      hydraulic conductivity at the reference temperature with a function that is
      linearly dependent on the CPA concentration. Consequently, the prediction of the
      Arrhenius relationship is improved, and the novel Arrhenius relationship could be
      very important to the development of optimal strategies for cell
      cryopreservation. 

PMID- 24023782
TI  - Cancer stem cell gene profile as predictor of relapse in high risk stage II and
      stage III, radically resected colon cancer patients.
AB  - Clinical data indicate that prognostic stratification of radically resected
      colorectal cancer based on disease stage only may not be always be adequate.
      Preclinical findings suggest that cancer stem cells may influence the biological
      behaviour of colorectal cancer independently from stage: objective of the study
      was to assess whether a panel of stemness markers were correlated with clinical
      outcome in resected stage II and III colon cancer patients. A panel of 66 markers
      of stemness were analysed and thus patients were divided into two groups (A and
      B) with most patients clustering in a manner consistent with different time to
      relapse by using a statistical algorithm. A total of 62 patients were analysed.
      Thirty-six (58%) relapsed during the follow-up period (range 1.63-86.5 months).
      Twelve (19%) and 50 (81%) patients were allocated into group A and B,
      respectively. A significantly different median relapse-free survival was observed
      between the 2 groups (22.18 vs 42.85 months, p=0.0296). Among of all genes
      tested, those with the higher "weight" in determining different prognosis were
      CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. This analysis
      supports the idea that, other than stage, biological variables, such as
      expression levels of colon cancer stem cell genes, may be relevant in determining
      an increased risk of relapse in resected colorectal cancer patients.

PMID- 24023783
TI  - Abolition of peroxiredoxin-5 mitochondrial targeting during canid evolution.
AB  - In human, the subcellular targeting of peroxiredoxin-5 (PRDX5), a thioredoxin
      peroxidase, is dependent on the use of multiple alternative transcription start
      sites and two alternative in-frame translation initiation sites, which determine
      whether or not the region encoding a mitochondrial targeting sequence (MTS) is
      translated. In the present study, the abolition of PRDX5 mitochondrial targeting
      in dog is highlighted and the molecular mechanism underlying the loss of
      mitochondrial PRDX5 during evolution is examined. Here, we show that the absence
      of mitochondrial PRDX5 is generalized among the extant canids and that the first
      events leading to PRDX5 MTS abolition in canids involve a mutation in the more 5'
      translation initiation codon as well as the appearance of a STOP codon.
      Furthermore, we found that PRDX5 MTS functionality is maintained in giant panda
      and northern elephant seal, which are phylogenetically closely related to canids.
      Also, the functional consequences of the restoration of mitochondrial PRDX5 in
      dog Madin-Darby canine kidney (MDCK) cells were investigated. The restoration of
      PRDX5 mitochondrial targeting in MDCK cells, instead of protecting, provokes
      deleterious effects following peroxide exposure independently of its peroxidase
      activity, indicating that mitochondrial PRDX5 gains cytotoxic properties under
      acute oxidative stress in MDCK cells. Altogether our results show that, although
      mitochondrial PRDX5 cytoprotective function against oxidative stress has been
      clearly demonstrated in human and rodents, PRDX5 targeting to mitochondria has
      been evolutionary lost in canids. Moreover, restoration of mitochondrial PRDX5 in
      dog MDCK cells, instead of conferring protection against peroxide exposure, makes
      them more vulnerable. 

PMID- 24023784
TI  - Critical roles of p53 in epithelial-mesenchymal transition and metastasis of
      hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) is one of the most malignant tumors and the
      biggest obstacle in curing HCC is its high metastasis potential. Alteration of
      p53 is the most frequent genetic change found in HCC. Although the biological
      function of p53 in tumor initiation and progression has been well characterized,
      whether or not p53 is implicated in metastasis of HCC is largely unknown. In this
      study, we analyzed the potential functions of p53 in epithelial-mesenchymal
      transition (EMT) and metastasis of HCC cells. Both insulin- and TGF-beta1-induced
      changes of critical EMT markers were greatly enhanced by p53 knockdown in HCC
      cells. The insulin- and TGF-beta1-stimulated migration of HCC cells were enhanced
      by p53 knockdown. Furthermore, in vivo metastasis of HCC cells using different
      mouse models was robustly enhanced by p53 knockdown. In addition, we found that
      p53 regulation on EMT and metastasis involves beta-catenin signaling. The nuclear
      accumulation and transcriptional activity of beta-catenin was modulated by p53.
      The enhanced EMT phenotype, cell migration and tumor metastasis of HCC cells by
      p53 knockdown were abrogated by inhibiting beta-catenin signal pathway. In
      conclusion, this study reveals that p53 plays a pivotal role in EMT and
      metastasis of HCC cells via its regulation on beta-catenin signaling. 

PMID- 24023785
TI  - Acid-base and electrolyte status during normovolemic hemodilution with
      succinylated gelatin or HES-containing volume replacement solutions in rats.
AB  - BACKGROUND: In the past, several studies have compared different colloidal
      replacement solutions, whereby the focus was usually on the respective colloid.
      We therefore systematically studied the influence of the carrier solution's
      composition of five approved colloidal volume replacement solutions (Gelafundin,
      Gelafusal, Geloplasma, Voluven and Volulyte) on acid-base as well as electrolyte
      status during and following acute severe normovolemic hemodilution. The solutions
      differed in the colloid used (succinylated gelatin vs. HES) and in the presence
      and concentration of metabolizable anions as well as in their electrolyte
      composition. METHODS: Anesthetized Wistar rats were subjected to a stepwise
      normovolemic hemodilution with one of the solutions until a final hematocrit of
      10%. Subsequent to dilution (162 min), animals were observed for an additional
      period (150 min). During dilution and observation time blood gas analyses were
      performed eight times in total. Additionally, in the Voluven and Volulyte groups
      as well as in 6 Gelafundin animals, electrolyte concentrations, glucose, pH and
      succinylated gelatin were measured in urine and histopathological evaluation of
      the kidney was performed. RESULTS: All animals survived without any indications
      of injury. Although the employed solutions differed in their respective
      composition, comparable results in all plasma acid-base and electrolyte
      parameters studied were obtained. Plasma pH increased from approximately 7.28 to
      7.39, the plasma K(+) concentration decreased from circa 5.20 mM to 4.80-3.90 mM
      and the plasma Cl(-) concentration rose from approximately 105 mM to 111-120 mM.
      Urinary analysis revealed increased excretion of K(+), H(+) and Cl(-).
      CONCLUSIONS: The present data suggest that the carrier solution's composition
      with regard to metabolizable anions as well as K(+), Ca(2+) only has a minor
      impact on acid-base and electrolyte status after application of succinylated
      gelatin or HES-containing colloidal volume replacement solutions.

PMID- 24023786
TI  - Effects of lipid-lowering drugs on irisin in human subjects in vivo and in human
      skeletal muscle cells ex vivo.
AB  - CONTEXT AND OBJECTIVE: The myokine irisin has been proposed to regulate energy
      homeostasis. Little is known about its association with metabolic parameters and
      especially with parameters influencing pathways of lipid metabolism. In the
      context of a clinical trial, an exploratory post hoc analysis has been performed
      in healthy subjects to determine whether simvastatin and/or ezetimibe influence
      serum irisin levels. The direct effects of simvastatin on irisin were also
      examined in primary human skeletal muscle cells (HSKMCs). DESIGN AND
      PARTICIPANTS: A randomized, parallel 3-group study was performed in 72 men with
      mild hypercholesterolemia and without apparent cardiovascular disease. Each group
      of 24 subjects received a 14-day treatment with either simvastatin 40 mg,
      ezetimibe 10 mg, or their combination. RESULTS: Baseline irisin concentrations
      were not significantly correlated with age, BMI, estimated GFR, thyroid
      parameters, glucose, insulin, lipoproteins, non-cholesterol sterols, adipokines,
      inflammation markers and various molecular markers of cholesterol metabolism.
      Circulating irisin increased significantly in simvastatin-treated but not in
      ezetimibe-treated subjects. The changes were independent of changes in LDL
      cholesterol and were not correlated with changes in creatine kinase levels. In
      HSKMCs, simvastatin significantly increased irisin secretion as well as mRNA
      expression of its parent peptide hormone FNDC5. Simvastatin significantly induced
      cellular reactive oxygen species levels along with expression of pro- and anti
      oxidative genes such as Nox2, and MnSOD and catalase, respectively. Markers of
      cellular stress such as atrogin-1 mRNA and Bax protein expression were also
      induced by simvastatin. Decreased cell viability and increased irisin secretion
      by simvastatin was reversed by antioxidant mito-TEMPO, implying in part that
      irisin is secreted as a result of increased mitochondrial oxidative stress and
      subsequent myocyte damage. CONCLUSIONS: Simvastatin increases irisin
      concentrations in vivo and in vitro. It remains to be determined whether this
      increase is a result of muscle damage or a protective mechanism against
      simvastatin-induced cellular stress. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00317993 NCT00317993.

PMID- 24023787
TI  - Impacts of pretransplant infections on clinical outcomes of patients with acute
      on-chronic liver failure who received living-donor liver transplantation.
AB  - BACKGROUND: Liver transplantation is the only therapeutic modality for patients
      with acute-on chronic liver failure (ACLF). These patients are at high risk for
      bacterial infections while awaiting transplantation. The aim of this study was to
      elucidate whether an adequately treated bacterial infection influences the
      outcomes after transplantation in this patient population. METHODOLOGY/PRINCIPAL
      FINDINGS: 54 recipients (median age, 49.5 years [range, 22-60]) of adult-to-adult
      living donor liver transplant (LDLT) for ACLF were categorized as those with
      pretransplant infection (Group 1, n=34) or without pretransplant infection (Group
      2, n=20) for retrospective analyses. With the exception of a higher male-female
      ratio (P=0.046) and longer length of pretransplant hospital stay (P=0.026) in
      Group 1, similar demographic, laboratory and clinical features were found in both
      groups. Patients in Group 1 (totally 42 pretransplant infection episodes) were
      adequately treated with effective antibiotic(s) before receiving LDLT. All
      included patients were followed up until one year after transplantation or death.
      Sixty-one posttransplant infection episodes were found in an overall of 44 ACLF
      patients (27 in Group 1 vs. 15 in Group 2; P=0.352). Frequently encountered
      posttransplant infections were intraabdominal infection, pneumonia, bloodstream
      infection and urinary tract infection. Two patients died in each group (P=0.622).
      No significant difference was found in the length of posttransplant ICU stay, and
      in one-year survival, graft rejection, and posttransplant infection rate between
      both groups. The longer overall hospital stay (mean day, 89.0 vs. 65.5, P=0.024)
      found in Group 1 resulted from a longer pretransplant hospital stay receiving
      treatment for pretransplant infection(s) and/or awaiting transplantation.
      CONCLUSIONS: These data suggested that an adequately treated pretransplant
      infection do not pose a significant risk for clinical outcomes including
      posttransplant fatality in recipients in adult-to-adult LDLT for ACLF.

PMID- 24023788
TI  - Gene network analysis in a pediatric cohort identifies novel lung function genes.
AB  - Lung function is a heritable trait and serves as an important clinical predictor
      of morbidity and mortality for pulmonary conditions in adults, however, despite
      its importance, no studies have focused on uncovering pediatric-specific loci
      influencing lung function. To identify novel genetic determinants of pediatric
      lung function, we conducted a genome-wide association study (GWAS) of four
      pulmonary function traits, including FVC, FEV1, FEV1/FVC and FEF25-75% in 1556
      children. Further, we carried out gene network analyses for each trait including
      all SNPs with a P-value of <1.0 * 10(-3) from the individual GWAS. The GWAS
      identified SNPs with notable trends towards association with the pulmonary
      function measures, including the previously described INTS12 locus association
      with FEV1 (pmeta=1.41 * 10(-7)). The gene network analyses identified 34 networks
      of genes associated with pulmonary function variables in Caucasians. Of those,
      the glycoprotein gene network reached genome-wide significance for all four
      variables. P-value range pmeta=6.29 * 10(-4) - 2.80 * 10(-8) on meta-analysis. In
      this study, we report on specific pathways that are significantly associated with
      pediatric lung function at genome-wide significance. In addition, we report the
      first loci associated with lung function in both pediatric Caucasian and African
      American populations.

PMID- 24023789
TI  - Impact of viral factors on subcellular distribution and RNA export activity of
      HIV-1 rev in astrocytes 1321N1.
AB  - CNS associated cells are permissive to HIV-1 infection, but poor in virus
      production due to attenuated Rev activity. The temporal and the spatial
      distribution of Rev in human astrocyte 1321N1 and glioblastoma GO-G-CCM were
      monitored for explaining the reduced Rev activity and low viral production during
      HIV-1 infection. Rev remained localized to the nuclei of these cells upon
      infection, attenuating its export activity, as manifested by low copy number of
      RRE-containing viral-mRNA in the cytoplasm of these cells. In contrast to
      infection, when Rev alone was transiently expressed, it localized in the
      cytoplasm of 1321N1. The localization changed to the nucleus when Rev was
      expressed in the presence of other viral proteins through pro-viral DNA pNL4-3.
      This study, for the first time, revealed the impact of other HIV-1 proteins apart
      from host factors in regulating the subcellular localization of Rev in astrocytes
      and hence the fate of HIV-1 infection in these cells. 

PMID- 24023790
TI  - Presence in the pre-surgical fine-needle aspiration of potential thyroid
      biomarkers previously identified in the post-surgical one.
AB  - Fine-needle aspiration biopsy (FNA) is usually applied to distinguish benign from
      malignant thyroid nodules. However, cytological analysis cannot always allow a
      proper diagnosis. We believe that the improvement of the diagnostic capability of
      pre-surgical FNA could avoid unnecessary thyroidectomy. In a previous study, we
      performed a proteome analysis to examine FNA collected after thyroidectomy. With
      the present study, we examined the applicability of these results on pre-surgical
      FNA. We collected pre-surgical FNA from 411 consecutive patients, and to obtain a
      correct comparison with our previous results, we processed only benign (n=114),
      papillary classical variant (cPTC) (n=34) and papillary tall cell variant (TcPTC)
      (n=14) FNA. We evaluated levels of five proteins previously found up-regulated in
      thyroid cancer with respect to benign nodules. ELISA and western blot (WB)
      analysis were used to assay levels of L-lactate dehydrogenase B chain (LDHB),
      Ferritin heavy chain, Ferritin light chain, Annexin A1 (ANXA1), and Moesin in
      FNA. ELISA assays and WB analysis confirmed the increase of LDHB, Moesin, and
      ANXA1 in pre-surgical FNA of thyroid papillary cancer. Sensitivity and
      specificity of ANXA1 were respectively 87 and 94% for cPTC, 85 and 100% for
      TcPTC. In conclusion, a proteomic analysis of FNA from patients with thyroid
      nodules may help to distinguish benign versus malignant thyroid nodules.
      Moreover, ANXA1 appears to be an ideal candidate given the high sensitivity and
      specificity obtained from ROC curve analysis.

PMID- 24023791
TI  - The usefulness of rapid diagnostic tests in the new context of low malaria
      transmission in Zanzibar.
AB  - BACKGROUND: We assessed if histidine-rich-protein-2 (HRP2) based rapid diagnostic
      test (RDT) remains an efficient tool for Plasmodium falciparum case detection
      among fever patients in Zanzibar and if primary health care workers continue to
      adhere to RDT results in the new epidemiological context of low malaria
      transmission. Further, we evaluated the performance of RDT within the newly
      adopted integrated management of childhood illness (IMCI) algorithm in Zanzibar.
      METHODS AND FINDINGS: We enrolled 3890 patients aged >= 2 months with
      uncomplicated febrile illness in this health facility based observational study
      conducted in 12 primary health care facilities in Zanzibar, between May-July
      2010. One patient had an inconclusive RDT result. Overall 121/3889 (3.1%)
      patients were RDT positive. The highest RDT positivity rate, 32/528 (6.1%), was
      found in children aged 5-14 years. RDT sensitivity and specificity against PCR
      was 76.5% (95% CI 69.0-83.9%) and 99.9% (95% CI 99.7-100%), and against blood
      smear microscopy 78.6% (95% CI 70.8-85.1%) and 99.7% (95% CI 99.6-99.9%),
      respectively. All RDT positive, but only 3/3768 RDT negative patients received
      anti-malarial treatment. Adherence to RDT results was thus 3887/3889 (99.9%). RDT
      performed well in the IMCI algorithm with equally high adherence among children
      <5 years as compared with other age groups. CONCLUSIONS: The sensitivity of HRP-2
      based RDT in the hands of health care workers compared with both PCR and
      microscopy for P. falciparum case detection was relatively low, whereas adherence
      to test results with anti-malarial treatment was excellent. Moreover, the results
      provide evidence that RDT can be reliably integrated in IMCI as a tool for
      improved childhood fever management. However, the relatively low RDT sensitivity
      highlights the need for improved quality control of RDT use in primary health
      care facilities, but also for more sensitive point-of-care malaria diagnostic
      tools in the new epidemiological context of low malaria transmission in Zanzibar.
      TRIAL REGISTRATION: ClinicalTrials.gov NCT01002066.

PMID- 24023792
TI  - SPLICEFINDER - a fast and easy screening method for active protein trans-splicing
      positions.
AB  - Split intein enabled protein trans-splicing (PTS) is a powerful method for the
      ligation of two protein fragments, thereby paving the way for various protein
      modification or protein function control applications. PTS activity is strongly
      influenced by the amino acids directly flanking the splice junctions. However, to
      date no reliable prediction can be made whether or not a split intein is active
      in a particular foreign extein context. Here we describe SPLICEFINDER, a PCR
      based method, allowing fast and easy screening for active split intein insertions
      in any target protein. Furthermore we demonstrate the applicability of
      SPLICEFINDER for segmental isotopic labeling as well as for the generation of
      multi-domain and enzymatically active proteins. 

PMID- 24023793
TI  - An efficient 3D cell culture method on biomimetic nanostructured grids.
AB  - Current techniques of in vitro cell cultures are able to mimic the in vivo
      environment only to a limited extent, as they enable cells to grow only in two
      dimensions. Therefore cell culture approaches should rely on scaffolds that
      provide support comparable to the extracellular matrix. Here we demonstrate the
      advantages of novel nanostructured three-dimensional grids fabricated using
      electro-spinning technique, as scaffolds for cultures of neoplastic cells. The
      results of the study show that the fibers allow for a dynamic growth of HeLa
      cells, which form multi-layer structures of symmetrical and spherical character.
      This indicates that the applied scaffolds are nontoxic and allow proper flow of
      oxygen, nutrients, and growth factors. In addition, grids have been proven to be
      useful in in situ examination of cells ultrastructure. 

PMID- 24023794
TI  - Response of Burkholderia cenocepacia H111 to micro-oxia.
AB  - B. cenocepacia is an opportunistic human pathogen that is particularly
      problematic for patients suffering from cystic fibrosis (CF). In the CF lung
      bacteria grow to high densities within the viscous mucus that is limited in
      oxygen. Pseudomonas aeruginosa, the dominant pathogen in CF patients, is known to
      grow and survive under oxygen-limited to anaerobic conditions by using micro-oxic
      respiration, denitrification and fermentative pathways. In contrast, inspection
      of the genome sequences of available B. cenocepacia strains suggested that B.
      cenocepacia is an obligate aerobic and non-fermenting bacterium. In accordance
      with the bioinformatics analysis we observed that B. cenocepacia H111 is able to
      grow with as little as 0.1% O2 but not under strictly anoxic conditions.
      Phenotypic analyses revealed that H111 produced larger amounts of biofilm,
      pellicle and proteases under micro-oxic conditions (0.5%-5% O2, i.e. conditions
      that mimic those encountered in CF lung infection), and was more resistant to
      several antibiotics. RNA-Seq and shotgun proteomics analyses of cultures of B.
      cenocepacia H111 grown under micro-oxic and aerobic conditions showed up
      regulation of genes involved in the synthesis of the exopolysaccharide (EPS)
      cepacian as well as several proteases, two isocitrate lyases and other genes
      potentially important for life in micro-oxia. DATA DEPOSITION: RNA-Seq raw data
      files are accessible through the GEO Series accession number GSE48585. MS data
      have been deposited in the ProteomeXchange database (PXD000270).

PMID- 24023795
TI  - Ashtrays and signage as determinants of a smoke-free legislation's success.
AB  - INTRODUCTION: Successful smoke-free legislation is dependent on political will,
      enforcement and societal support. We report the success and pitfalls of a non
      enforced nationwide smoke-free legislation in Greece, as well as ways in which
      compliance and enforcement-related factors, including ashtrays and signage, may
      impact indoor secondhand smoke (SHS) concentrations. METHODS: A follow-up study
      of venues (n=150, at baseline, n=75 at 2-year follow-up) in Greece assessed
      indoor particulate matter with a diameter less than 2.5 micrometers (PM 2.5 )
      concentrations attributable to SHS smoke every six months for two years (n=455
      venue/measurements). RESULTS: Following the implementation of the 2010 smoke-free
      legislation, mean PM2.5 concentrations attributable to SHS fell from 175.3
      ug/m(3) pre-ban to 84.52 ug/m(3) immediately post-ban, increasing over subsequent
      waves (103.8 ug/m(3) and 158.2 ug/m(3) respectively). Controlling for potential
      influential factors such as ventilation, time of day, day of week, city and venue
      type, all post-ban measurements were still lower than during the pre-ban period
      (Wave 2 beta: -118.7, Wave 3 beta: -87.6, and Wave 4 beta: -69.9). Outdoor or
      indoor signage banning smoking was not found to affect SHS concentrations (beta: 
      10.9, p=0.667 and beta: -18.1, p=0.464 respectively). However, ashtray or ashtray
      equivalents were strong determinants of the existence of indoor SHS (beta: +67
      ug/m(3), p=0.017). CONCLUSIONS: While the public may be supportive of smoke-free
      legislation, adherence may decline rapidly if enforcement is limited or
      nonexistent. Moreover, enforcement agencies should also focus on the
      comprehensive removal of ashtray equivalents that could act as cues for smoking
      within a venue.

PMID- 24023796
TI  - Housing first reduces re-offending among formerly homeless adults with mental
      disorders: results of a randomized controlled trial.
AB  - BACKGROUND: Homelessness and mental illness have a strong association with public
      disorder and criminality. Experimental evidence indicates that Housing First (HF)
      increases housing stability and perceived choice among those experiencing chronic
      homelessness and mental disorders. HF is also associated with lower residential
      costs than common alternative approaches. Few studies have examined the effect of
      HF on criminal behavior. METHODS: Individuals meeting criteria for homelessness
      and a current mental disorder were randomized to one of three conditions
      treatment as usual (reference); scattered site HF; and congregate HF.
      Administrative data concerning justice system events were linked in order to
      study prior histories of offending and to test the relationship between housing
      status and offending following randomization for up to two years. RESULTS: The
      majority of the sample (67%) was involved with the justice system, with a mean of
      8.07 convictions per person in the ten years prior to recruitment. The most
      common category of crime was "property offences" (mean=4.09). Following
      randomization, the scattered site HF condition was associated with significantly
      lower numbers of sentences than treatment as usual (Adjusted IRR=0.29; 95% CI
      0.12-0.72). Congregate HF was associated with a marginally significant reduction
      in sentences compared to treatment as usual (Adjusted IRR=0.55; 95% CI: 0.26
      1.14). CONCLUSIONS: This study is the first randomized controlled trial to
      demonstrate benefits of HF among a homeless sample with mental illness in the
      domain of public safety and crime. Our sample was frequently involved with the
      justice system, with great personal and societal costs. Further implementation of
      HF is strongly indicated, particularly in the scattered site format. Research
      examining interdependencies between housing, health, and the justice system is
      indicated. TRIAL REGISTRATION: ISRCTN57595077.

PMID- 24023797
TI  - The human gastrointestinal tract, a potential autologous neural stem cell source.
AB  - Stem cell therapies seem to be an appropriate tool for the treatment of a variety
      of diseases, especially when a substantial cell loss leads to a severe clinical
      impact. This is the case in most neuronal cell losses. Unfortunately, adequate
      neural stem cell sources are hard to find and current alternatives, such as
      induced programmed stem cells, still have incalculable risks. Evidence of
      neurogenesis in the adult human enteric nervous system brought up a new
      perspective. In humans the appendix harbors enteric neuronal tissue and is an
      ideal location where the presence of neural stem cells is combined with a minimal
      invasive accessibility. In this study appendices from adults and children were
      investigated concerning their neural stem cell potential. From each appendix
      tissue samples were collected, and processed for immunohistochemistry or enteric
      neural progenitor cell generation. Free-floating enteric neurospheres (EnNS's)
      could be generated after 6 days in vitro. EnNS's were either used for
      transplantation into rat brain slices or differentiation experiments. Both
      transplanted spheres and control cultures developed an intricate network with
      glia, neurons and interconnecting fibers, as seen in primary enteric cultures
      before. Neuronal, glial and neural stem cell markers could be identified both in
      vitro and in vivo by immunostaining. The study underlines the potential of the
      enteric nervous system as an autologous neural stem cell source. Using the
      appendix as a potential target opens up a new perspective that might lead to a
      relatively unproblematic harvest of neural stem cells. 

PMID- 24023799
TI  - Lack of genetic differentiation between contrasted overwintering strategies of a
      major pest predator Episyrphus balteatus (Diptera: Syrphidae): implications for
      biocontrol.
AB  - Winter ecology of natural enemies has a great influence on the level and
      efficiency of biological control at spring. The hoverfly Episyrphus balteatus
      (DeGeer) (Diptera: Syrphidae) is one of the most important natural predators of
      crop aphids in Europe. Three different overwintering strategies coexist in this
      species which makes it a good model in order to study ecologically-based
      speciation processes. The purpose of this study was to determine whether E.
      balteatus populations with alternative overwintering strategies are genetically
      differentiated. To that aim, we developed 12 specific microsatellite markers and
      evaluated the level of neutral genetic differentiation between E. balteatus field
      populations that overwinter in the three different ways described in this species
      (i.e. migration, local overwintering at a pre-imaginal stage, and local
      overwintering at adult stage). Results showed a lack of neutral genetic
      differentiation between individuals with different overwintering strategies
      although there are strong ecological differences between them. All pair-wise FST
      values are below 0.025 and non-significant, and Bayesian clustering showed K=1
      was the most likely number of genetic clusters throughout our sample. The three
      overwintering strategies form one unique panmictic population. This suggests that
      all the individuals may have genetic material for the expression of different
      overwintering phenotypes, and that their commitment in one particular
      overwintering strategy may depend on environmental and individual factors.
      Consequently, the prevalence of the different overwintering strategies would be
      potentially modified by landscape engineering and habitat management which could
      have major implications for biological control.

PMID- 24023798
TI  - Spiral-wave dynamics in a mathematical model of human ventricular tissue with
      myocytes and fibroblasts.
AB  - Cardiac fibroblasts, when coupled functionally with myocytes, can modulate the
      electrophysiological properties of cardiac tissue. We present systematic
      numerical studies of such modulation of electrophysiological properties in
      mathematical models for (a) single myocyte-fibroblast (MF) units and (b) two
      dimensional (2D) arrays of such units; our models build on earlier ones and allow
      for zero-, one-, and two-sided MF couplings. Our studies of MF units elucidate
      the dependence of the action-potential (AP) morphology on parameters such as
      [Formula: see text], the fibroblast resting-membrane potential, the fibroblast
      conductance [Formula: see text], and the MF gap-junctional coupling [Formula: see
      text]. Furthermore, we find that our MF composite can show autorhythmic and
      oscillatory behaviors in addition to an excitable response. Our 2D studies use
      (a) both homogeneous and inhomogeneous distributions of fibroblasts, (b) various
      ranges for parameters such as [Formula: see text], and [Formula: see text], and
      (c) intercellular couplings that can be zero-sided, one-sided, and two-sided
      connections of fibroblasts with myocytes. We show, in particular, that the plane
      wave conduction velocity [Formula: see text] decreases as a function of [Formula:
      see text], for zero-sided and one-sided couplings; however, for two-sided
      coupling, [Formula: see text] decreases initially and then increases as a
      function of [Formula: see text], and, eventually, we observe that conduction
      failure occurs for low values of [Formula: see text]. In our homogeneous studies,
      we find that the rotation speed and stability of a spiral wave can be controlled
      either by controlling [Formula: see text] or [Formula: see text]. Our studies
      with fibroblast inhomogeneities show that a spiral wave can get anchored to a
      local fibroblast inhomogeneity. We also study the efficacy of a low-amplitude
      control scheme, which has been suggested for the control of spiral-wave
      turbulence in mathematical models for cardiac tissue, in our MF model both with
      and without heterogeneities. 

PMID- 24023800
TI  - Reference gene selection and validation for the early responses to downy mildew
      infection in susceptible and resistant Vitis vinifera cultivars.
AB  - The pivotal role of cultivated grapevine (Vitis vinifera L.) in many countries
      economy is compromised by its high susceptibility to Plasmopara viticola, the
      causal agent of downy mildew disease. Recent research has identified a set of
      genes related to resistance which may be used to track downy mildew infection.
      Quantification of the expression of these resistance genes requires normalizing
      qPCR data using reference genes with stable expression in the system studied. In
      this study, a set of eleven genes (VATP16, 60 S, UQCC, SMD3, EF1alpha, UBQ, SAND,
      GAPDH, ACT, PsaB, PTB2) was evaluated to identify reference genes during the
      first hours of interaction (6, 12, 18 and 24 hpi) between two V. vinifera
      genotypes and P. viticola. Two analyses were used for the selection of reference
      genes: direct comparison of susceptible, Trincadeira, and resistant, Regent, V.
      vinifera cultivars at 0 h, 6, 12, 18 and 24 hours post inoculation with P.
      viticola (genotype effect); and comparison of each genotype with mock inoculated
      samples during inoculation time-course (biotic stress effect). Three statistical
      methods were used, GeNorm, NormFinder, and BestKeeper, allowing to identify UBQ,
      EF1alpha and GAPDH as the most stable genes for the genotype effect. For the
      biotic stress effect, EF1alpha, SAND and SMD3 were the most constant for the
      susceptible cultivar Trincadeira and EF1alpha, GAPDH, UBQ for the resistant
      cultivar Regent. In addition, the expression of three defense-related
      transcripts, encoding for subtilisin-like protein, CYP and PR10, was analysed,
      for both datasets, during inoculation time-course. Taken together, our results
      provide guidelines for reference gene(s) selection towards a more accurate and
      widespread use of qPCR to study the first hours of interaction between different
      grapevine cultivars and P. viticola. 

PMID- 24023801
TI  - Neuron glia-related cell adhesion molecule (NrCAM) promotes topographic
      retinocollicular mapping.
AB  - NrCAM (Neuron-glial related cell adhesion molecule), a member of the L1 family of
      cell adhesion molecules, reversibly binds ankyrin and regulates axon growth, but
      it has not been studied for a role in retinotopic mapping. During development of
      retino-collicular topography, NrCAM was expressed uniformly in retinal ganglion
      cells (RGCs) along both mediolateral and anteroposterior retinal axes, and was
      localized on RGC axons within the optic tract and superior colliculus (SC).
      Anterograde tracing of RGC axons in NrCAM null mutant mice at P10, when the map
      resembles its mature form, revealed laterally displaced ectopic termination zones
      (eTZs) of axons from the temporal retina, indicating defective mediolateral
      topography, which is governed by ephrinB/EphBs. Axon tracing at P2 revealed that
      interstitial branch orientation of ventral-temporal RGC axons in NrCAM null mice
      was compromised in the medial direction, likely accounting for displacement of
      eTZs. A similar retinocollicular targeting defect in EphB mutant mice suggested
      that NrCAM and EphB interact to regulate mediolateral retino-collicular
      targeting. We found that EphB2 tyrosine kinase but not an EphB2 kinase dead
      mutant, phosphorylated NrCAM at a conserved tyrosine residue in the FIGQY ankyrin
      binding motif, perturbing ankyrin recruitment in NrCAM transfected HEK293 cells.
      Furthermore, the phosphorylation of NrCAM at FIGQY in SC was decreased in EphB1/3
      and EphB1/2/3 null mice compared to WT, while phospho-FIGQY of NrCAM in SC was
      increased in EphB2 constitutively active (F620D/F620D) mice. These results
      demonstrate that NrCAM contributes to mediolateral retinocollicular axon
      targeting by regulating RGC branch orientation through a likely mechanism in
      which ephrinB/EphB phosphorylates NrCAM to modulate linkage to the actin
      cytoskeleton. 

PMID- 24023803
TI  - A longitudinal study of memory advantages in bilinguals.
AB  - Typically, studies of cognitive advantages in bilinguals have been conducted
      previously by using executive and inhibitory tasks (e.g. Simon task) and applying
      cross-sectional designs. This study longitudinally investigated bilingual
      advantages on episodic memory recall, verbal letter and categorical fluency
      during the trajectory of life. Monolingual and bilingual participants (n=178)
      between 35-70 years at baseline were drawn from the Betula Prospective Cohort
      Study of aging, memory, and health. Results showed that bilinguals outperformed
      monolinguals at the first testing session and across time both in episodic memory
      recall and in letter fluency. No interaction with age was found indicating that
      the rate of change across ages was similar for bilinguals and monolinguals. As
      predicted and in line with studies applying cross-sectional designs, no
      advantages associated with bilingualism were found in the categorical fluency
      task. The results are discussed in the light of successful aging.

PMID- 24023802
TI  - IKKalpha/CHUK regulates extracellular matrix remodeling independent of its kinase
      activity to facilitate articular chondrocyte differentiation.
AB  - BACKGROUND: The non-canonical NF-kappaB activating kinase IKKalpha, encoded by
      CHUK (conserved-helix-loop-helix-ubiquitous-kinase), has been reported to
      modulate pro- or anti- inflammatory responses, cellular survival and cellular
      differentiation. Here, we have investigated the mechanism of action of IKKalpha
      as a novel effector of human and murine chondrocyte extracellular matrix (ECM)
      homeostasis and differentiation towards hypertrophy. METHODOLOGY/PRINCIPAL
      FINDINGS: IKKalpha expression was ablated in primary human osteoarthritic (OA)
      chondrocytes and in immature murine articular chondrocytes (iMACs) derived from
      IKKalpha(f/f):CreERT2 mice by retroviral-mediated stable shRNA transduction and
      Cre recombinase-dependent Lox P site recombination, respectively. MMP-10 was
      identified as a major target of IKKalpha in chondrocytes by mRNA profiling,
      quantitative RT-PCR analysis, immunohistochemistry and immunoblotting. ECM
      integrity, as assessed by type II collagen (COL2) deposition and the lack of MMP
      dependent COL2 degradation products, was enhanced by IKKalpha ablation in mice.
      MMP-13 and total collagenase activities were significantly reduced, while TIMP-3
      (tissue inhibitor of metalloproteinase-3) protein levels were enhanced in
      IKKalpha-deficient chondrocytes. IKKalpha deficiency suppressed chondrocyte
      differentiation, as shown by the quantitative inhibition of.Alizarin red staining
      and the reduced expression of multiple chondrocyte differentiation effectors,
      including Runx2, Col10a1 and Vegfa,. Importantly, the differentiation of IKKalpha
      deficient chondrocytes was rescued by a kinase-dead IKKalpha protein mutant.
      CONCLUSIONS/SIGNIFICANCE: IKKalpha acts independent of its kinase activity to
      help drive chondrocyte differentiation towards a hypertrophic-like state.
      IKKalpha positively modulates ECM remodeling via multiple downstream targets
      (including MMP-10 and TIMP-3 at the mRNA and post-transcriptional levels,
      respectively) to maintain maximal MMP-13 activity, which is required for ECM
      remodeling leading to chondrocyte differentiation. Chondrocytes are the unique
      cell component in articular cartilage, which are quiescent and maintain ECM
      integrity during tissue homeostasis. In OA, chondrocytes reacquire the capacity
      to proliferate and differentiate and their activation results in pronounced
      cartilage degeneration. Tauetaupsilonsigma, our findings are also of potential
      relevance for defining the onset and/or progression of OA disease.

PMID- 24023804
TI  - Unraveling the protein network of tomato fruit in response to necrotrophic
      phytopathogenic Rhizopus nigricans.
AB  - Plants are endowed with a sophisticated defense mechanism that gives signals to
      plant cells about the immediate danger from surroundings and protects them from
      pathogen invasion. In the search for the particular proteins involved in fruit
      defense responses, we report here a comparative analysis of tomato fruit (Solanum
      lycopersicum cv. Ailsa Craig) infected by Rhizopus nigricans Ehrenb, which is a
      significant contributor to postharvest rot disease in fresh tomato fruits. In
      total, four hundred forty-five tomato proteins were detected in common between
      the non-infected group and infected tomato fruit of mature green. Forty-nine
      differentially expressed spots in 2-D gels were identified, and were sorted into
      fifteen functional groups. Most of these proteins participate directly in the
      stress response process, while others were found to be involved in several
      equally important biological processes: protein metabolic process, carbohydrate
      metabolic process, ethylene biosynthesis, and cell death and so on. These
      responses occur in different cellular components, both intra- and extracellular
      spaces. The differentially expressed proteins were integrated into several
      pathways to show the regulation style existing in tomato fruit host. The
      composition of the collected proteins populations and the putative functions of
      the identified proteins argue for their roles in pathogen-plant interactions.
      Collectively results provide evidence that several regulatory pathways contribute
      to the resistance of tomato fruit to pathogen. 

PMID- 24023805
TI  - Three-year-olds' understanding of the consequences of joint commitments.
AB  - Here we investigate the extent of children's understanding of the joint
      commitments inherent in joint activities. Three-year-old children either made a
      joint commitment to assemble a puzzle with a puppet partner, or else the child
      and puppet each assembled their own puzzle. Afterwards, children who had made the
      joint commitment were more likely to stop and wait for their partner on their way
      to fetch something, more likely to spontaneously help their partner when needed,
      and more likely to take over their partner's role when necessary. There was no
      clear difference in children's tendency to tattle on their partner's cheating
      behavior or their tendency to distribute rewards equally at the end. It thus
      appears that by 3 years of age making a joint commitment to act together with
      others is beginning to engender in children a "we"-intentionality which holds
      across at least most of the process of the joint activity until the shared goal
      is achieved, and which withstands at least some of the perturbations to the joint
      activity children experience. 

PMID- 24023806
TI  - Head rubbing and licking reinforce social bonds in a group of captive African
      lions, Panthera leo.
AB  - Many social animals have a species-specific repertoire of affiliative behaviours
      that characterise individualised relationships within a group. To date, however,
      quantitative studies on intragroup affiliative behaviours in social carnivores
      have been limited. Here, we investigated the social functions of the two most
      commonly observed affiliative behaviours in captive African lions (Panthera leo):
      head rubbing and licking. We conducted behavioural observations on a captive
      group of lions composed of 7 males and 14 females, and tested hypotheses
      regarding three social functions: tension reduction, social bonding, and social
      status expression. Disproportionately frequent male-male and female-to-male head
      rubbing was observed, while more than 95% of all licking interactions occurred in
      female-female dyads. In accordance with the social bond hypothesis, and in
      disagreement with the social status expression hypothesis, both head rubbing and
      licking interactions were reciprocal. After controlling for spatial association,
      the dyadic frequency of head rubbing was negatively correlated with age
      difference while licking was positively correlated with relatedness. Group
      reunion after daily separation did not affect the frequencies of the affiliative
      behaviours, which was in disagreement with the predictions from the tension
      reduction hypothesis. These results support the social bond hypothesis for the
      functions of head rubbing and licking. Different patterns of affiliative
      behaviour between the sexes may reflect differences in the relationship quality
      in each sex or the differential predisposition to licking due to its original
      function in offspring care. 

PMID- 24023808
TI  - Metagenomic predictions: from microbiome to complex health and environmental
      phenotypes in humans and cattle.
AB  - Mammals have a large cohort of endo- and ecto- symbiotic microorganisms (the
      microbiome) that potentially influence host phenotypes. There have been numerous
      exploratory studies of these symbiotic organisms in humans and other animals,
      often with the aim of relating the microbiome to a complex phenotype such as body
      mass index (BMI) or disease state. Here, we describe an efficient methodology for
      predicting complex traits from quantitative microbiome profiles. The method was
      demonstrated by predicting inflammatory bowel disease (IBD) status and BMI from
      human microbiome data, and enteric greenhouse gas production from dairy cattle
      rumen microbiome profiles. The method uses unassembled massively parallel
      sequencing (MPS) data to form metagenomic relationship matrices (analogous to
      genomic relationship matrices used in genomic predictions) to predict IBD, BMI
      and methane production phenotypes with useful accuracies (r = 0.423, 0.422 and
      0.466 respectively). Our results show that microbiome profiles derived from MPS
      can be used to predict complex phenotypes of the host. Although the number of
      biological replicates used here limits the accuracy that can be achieved,
      preliminary results suggest this approach may surpass current prediction
      accuracies that are based on the host genome. This is especially likely for
      traits that are largely influenced by the gut microbiota, for example digestive
      tract disorders or metabolic functions such as enteric methane production in
      cattle.

PMID- 24023807
TI  - Hormonal contraception is associated with a reduced risk of bacterial vaginosis:
      a systematic review and meta-analysis.
AB  - OBJECTIVE: To examine the association between hormonal contraception (HC) and
      bacterial vaginosis (BV) by systematic review and meta-analysis. METHODS:
      Medline, Web of Science and Embase databases were searched to 24/1/13 and
      duplicate references removed. Inclusion criteria 1) >20 BV cases; 2) accepted BV
      diagnostic method; 3) measure of HC-use either as combined oestrogen-progesterone
      HC (combined), progesterone-only contraception (POC) or unspecified HC (u-HC); 4)
      >= 10% of women using HC; 5) analysis of the association between BV and HC-use
      presented; 6) appropriate control group. Data extracted included: type of HC, BV
      diagnostic method and outcome (prevalent, incident, recurrent), and geographical
      and clinic-setting. Meta-analyses were conducted to calculate pooled effect sizes
      (ES), stratified by HC-type and BV outcome. This systematic review is registered
      with PROSPERO (CRD42013003699). RESULTS: Of 1713 unique references identified,
      502 full-text articles were assessed for eligibility and 55 studies met inclusion
      criteria. Hormonal contraceptive use was associated with a significant reduction
      in the odds of prevalent BV (pooled effect size by random-effects [reES] = 0.68,
      95%CI0.63-0.73), and in the relative risk (RR) of incident (reES = 0.82,
      95%CI:0.72-0.92), and recurrent (reES = 0.69, 95%CI:0.59-0.91) BV. When
      stratified by HC-type, combined-HC and POC were both associated with decreased
      prevalence of BV and risk of incident BV. In the pooled analysis of the effect of
      HC-use on the composite outcome of prevalent/incident/recurrent BV, HC-use was
      associated with a reduced risk of any BV (reES = 0.78, 95%CI:0.74-0.82).
      CONCLUSION: HC-use was associated with a significantly reduced risk of BV. This
      negative association was robust and present regardless of HC-type and evident
      across all three BV outcome measures. When stratified by HC-type, combined-HC and
      POC were both individually associated with a reduction in the prevalence and
      incidence of BV. This meta-analysis provides compelling evidence that HC-use
      influences a woman's risk of BV, with important implications for clinicians and
      researchers in the field.

PMID- 24023809
TI  - A novel Bayesian seamless phase I/II design.
AB  - This paper proposes a novel bayesian phase I/II design featuring using a hybrid
      mTPI method in phase I for targeting the MTD level and a randomization allocation
      schema for adaptively assigning patients to desirable doses in phase II. The
      mechanism of simultaneously escalating dose in phase I and expanding promising
      doses to phase II is inherited from a design proposed in literature. Extensive
      simulation studies indicate that our proposed design can vastly save sample size
      and efficiently assign more patients to optimal dose when compared to two
      competing designs. 

PMID- 24023810
TI  - Ablation of the ID2 gene results in altered circadian feeding behavior, and sex
      specific enhancement of insulin sensitivity and elevated glucose uptake in
      skeletal muscle and brown adipose tissue.
AB  - Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor
      rhythmically expressed in many adult tissues. Our earlier studies have
      demonstrated a role for ID2 in the input pathway, core clock function and output
      pathways of the mouse circadian system. We have also reported that Id2 null (Id2
      /-) mice are lean with low gonadal white adipose tissue deposits and lower lipid
      content in the liver. These results coincided with altered or disrupted circadian
      expression profiles of liver genes including those involved in lipid metabolism.
      In the present phenotypic study we intended to decipher, on a sex-specific basis,
      the role of ID2 in glucose metabolism and in the circadian regulation of
      activity, important components of energy balance. We find that Id2-/- mice
      exhibited altered daily and circadian rhythms of feeding and locomotor activity;
      activity profiles extended further into the late night/dark phase of the 24-hr
      cycle, despite mice showing reduced total locomotor activity. Also, male Id2-/-
      mice consumed a greater amount of food relative to body mass, and displayed less
      weight gain. Id2-/- females had smaller adipocytes, suggesting sexual-dimorphic
      programing of adipogenesis. We observed increased glucose tolerance and insulin
      sensitivity in male Id2-/- mice, which was exacerbated in older animals. FDG-PET
      analysis revealed increased glucose uptake by skeletal muscle and brown adipose
      tissue of male Id2-/- mice, suggesting increased glucose metabolism and
      thermogenesis in these tissues. Reductions in intramuscular triacylglycerol and
      diacylglycerol were detected in male Id2-/- mice, highlighting its possible
      mechanistic role in enhanced insulin sensitivity in these mice. Our findings
      indicate a role for ID2 as a regulator of glucose and lipid metabolism, and in
      the circadian control of feeding/locomotor behavior; and contribute to the
      understanding of the development of obesity and diabetes, particularly in shift
      work personnel among whom incidence of such metabolic disorders is elevated. 

PMID- 24023811
TI  - Intermittent preventive therapy with sulfadoxine-pyrimethamine for malaria in
      pregnancy: a cross-sectional study from Tororo, Uganda.
AB  - BACKGROUND: Intermittent preventive treatment during pregnancy (IPTp) with
      sulfadoxine-pyrimethamine (SP) is widely recommended in sub-Saharan Africa to
      reduce the risk of malaria and improve birth outcomes. However, there are reports
      that the efficacy of IPTp with SP is waning, especially in parts of Africa where
      antimalarial resistance to this drug has become widespread. METHODOLOGY/PRINCIPAL
      FINDINGS: We conducted a cross-sectional study of 565 HIV-uninfected women giving
      birth at Tororo District Hospital in southeastern Uganda. The primary objective
      of the study was to measure associations between use of SP during pregnancy from
      antenatal records and the risk of adverse outcomes including placental malaria,
      low birth weight, maternal parasitemia and maternal anemia. The proportion of
      women who reported taking 0, 1, 2, and 3 doses of SP during pregnancy was 5.7%,
      35.8%, 56.6% and 2.0% respectively. Overall, the prevalence of placental malaria
      was 17.5%, 28.1%, and 66.2% by placental smear, PCR, and histopathology,
      respectively. In multivariate analyses controlling for potential confounders, >=
      2 doses of SP was associated with non-significant trends towards lower odds of
      placental malaria by placental smear (OR = 0.75, p = 0.25), placental malaria by
      PCR (OR = 0.93, p = 0.71), placental malaria by histopathology (OR = 0.75, p =
      0.16), low birth weight (OR = 0.63, p = 0.11), maternal parasitemia (OR = 0.88, p
      = 0.60) and maternal anemia (OR = 0.88, p = 0.48). Using a composite outcome, >=
      2 doses of SP was associated with a significantly lower odds of placental
      malaria, low birth weight, maternal parasitemia, or maternal anemia (OR = 0.52, p
      = 0.01). CONCLUSIONS/SIGNIFICANCE: In this area of Uganda with intense malaria
      transmission, the prevalence of placental malaria by histopathology was high even
      among women who reported taking at least 2 doses of SP during pregnancy. The
      reported use of >= 2 doses of SP was not associated with protection against
      individual birth and maternal outcome measures but did protect against a
      composite measure of any adverse outcome.

PMID- 24023812
TI  - The human urine metabolome.
AB  - Urine has long been a "favored" biofluid among metabolomics researchers. It is
      sterile, easy-to-obtain in large volumes, largely free from interfering proteins
      or lipids and chemically complex. However, this chemical complexity has also made
      urine a particularly difficult substrate to fully understand. As a biological
      waste material, urine typically contains metabolic breakdown products from a wide
      range of foods, drinks, drugs, environmental contaminants, endogenous waste
      metabolites and bacterial by-products. Many of these compounds are poorly
      characterized and poorly understood. In an effort to improve our understanding of
      this biofluid we have undertaken a comprehensive, quantitative, metabolome-wide
      characterization of human urine. This involved both computer-aided literature
      mining and comprehensive, quantitative experimental assessment/validation. The
      experimental portion employed NMR spectroscopy, gas chromatography mass
      spectrometry (GC-MS), direct flow injection mass spectrometry (DFI/LC-MS/MS),
      inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid
      chromatography (HPLC) experiments performed on multiple human urine samples. This
      multi-platform metabolomic analysis allowed us to identify 445 and quantify 378
      unique urine metabolites or metabolite species. The different analytical
      platforms were able to identify (quantify) a total of: 209 (209) by NMR, 179 (85)
      by GC-MS, 127 (127) by DFI/LC-MS/MS, 40 (40) by ICP-MS and 10 (10) by HPLC. Our
      use of multiple metabolomics platforms and technologies allowed us to identify
      several previously unknown urine metabolites and to substantially enhance the
      level of metabolome coverage. It also allowed us to critically assess the
      relative strengths and weaknesses of different platforms or technologies. The
      literature review led to the identification and annotation of another 2206
      urinary compounds and was used to help guide the subsequent experimental studies.
      An online database containing the complete set of 2651 confirmed human urine
      metabolite species, their structures (3079 in total), concentrations, related
      literature references and links to their known disease associations are freely
      available at http://www.urinemetabolome.ca. 

PMID- 24023813
TI  - Expression of legumain correlates with prognosis and metastasis in gastric
      carcinoma.
AB  - OBJECTIVE: Legumain, a novel asparaginyl endopeptidase, has been observed to be
      highly expressed in several types of tumors, which may play a vital role in
      carcinogenesis. However, there is no study investigating the relationship among
      Legumain expression, clinicopathologic, biological variables and patient
      prognosis in gastric carcinoma. METHODS: In this study, a tissue microarray (TMA)
      containing 282 samples of primary gastric cancer was assessed for Legumain
      expression by immunohistochemistry. The TMA included 98 lymph node metastasis
      samples. The protein expression levels of Legumain were evaluated by Western blot
      analysis. RESULTS: Cytoplasmic immunoreactivity of Legumain was over-expressed in
      gastric cancer compared with paired normal gastric mucosa. Increased Legumain
      levels were significantly correlated with clinical stage, presence of distant
      metastasis. Legumain was significantly over-expressed in primary gastric cancer
      with metastasis than without metastasis. Patients with Legumain-positive
      localized tumors had lower 5-year overall survival (OS) than those with Legumain
      negative tumors. Multivariate survival analysis showed that Legumain was an
      independent prognostic marker for OS (HR 1.459, 95% CI 1.251-1.703, P = 0.007).
      CONCLUSIONS: Legumain expression could serve as a prognostic biomarker in
      patients at risk of developing metastasis or recurrence with gastric carcinoma.

PMID- 24023814
TI  - Evaluation of PCR in bronchoalveolar lavage fluid for diagnosis of Pneumocystis
      jirovecii pneumonia: a bivariate meta-analysis and systematic review.
AB  - BACKGROUND: As a promising tool, PCR in bronchoalveolar lavage fluid (BALF) has
      not been accepted as a diagnostic criterion for PJP. OBJECTIVE: We undertook a
      systematic review of published studies to evaluate the diagnostic accuracy of PCR
      assays in BALF for PJP. METHODS: Eligible studies from PubMed, Embase and Web of
      Science reporting PCR assays in BALF for diagnosing PJP were identified. A
      bivariate meta-analysis of the method's sensitivity, specificity, and positive
      and negative likelihood ratios with a 95% confidence interval (CI) were analyzed.
      The post-test probability was performed to evaluate clinical usefulness. A
      summary receiver operating characteristics (SROC) curve was used to evaluate
      overall performance. Subgroup analyses were carried out to analysis the potential
      heterogeneity. RESULTS: Sixteen studies published between 1994 and 2012 were
      included. The summary sensitivity and specificity values (95% CI) of PCR in BALF
      for diagnosis of PJP were 98.3% (91.3%-99.7%) and 91.0% (82.7%-95.5%),
      respectively. The positive and negative likelihood ratios were 10.894 (5.569
      21.309) and 0.018 (0.003-0.099), respectively. In a setting of 20% prevalence of
      PJP, the probability of PJP would be over 3-fold if the BALF-PCR test was
      positive, and the probability of PJP would be less than 0.5% if it was negative.
      The area under the SROC curve was 0.98 (0.97-0.99). CONCLUSIONS: The method of
      PCR in BALF shows high sensitivity and good specificity for the diagnosis of PJP.
      However, clinical practice for the diagnosis of PJP should consider the
      consistent respiratory symptoms, radiographic changes and laboratory findings of
      the suspected patients.

PMID- 24023815
TI  - Genetic variation in PSCA and risk of gastric advanced preneoplastic lesions and
      cancer in relation to Helicobacter pylori infection.
AB  - SNPs in the Prostate Stem Cell Antigen (PSCA) gene have been found associated
      with gastric cancer (GC) risk in a genome-wide association study. This
      association has been replicated in several populations. In this study we assessed
      the impact of PSCA genotype on the risk of advanced gastric precancerous lesions
      and GC. We used baseline gastric histopathology data and DNA from frozen gastric
      biopsies of 2045 subjects enrolled in a chemoprevention trial for gastric
      precancerous lesions in Venezuela, and 180 cases of GC from the same area. We
      analyzed 3 SNPs in the PSCA gene (rs2294008, rs9297976 and rs12155758) which were
      previously found to be associated with GC risk in Europeans. The T allele of
      rs2294008 was found to be associated with a higher prevalence of atrophic
      gastritis (OR = 1.44; 95% CI 1.03-2.01 for the dominant model) and intestinal
      metaplasia (OR = 1.50; 95% CI 1.13-1.98 for the dominant model). We also
      confirmed the association with higher risk of gastric cancer (OR = 2.34; 95% CI
      1.36-4.01 for the allele carriers). SNP rs12155758 was not associated with risk
      of gastric preneoplastic lesions, but we confirmed its association with higher GC
      risk (OR 1.95; 95% CI 1.29-2.97 for dominant model). We tested the relevance of
      the presence of the Helicobacter pylori cagA gene, which is known to increase the
      risk of more severe gastric lesions, but we did not find any clearcut interaction
      with PSCA SNPs in defining risk of gastric precancerous lesions or cancer.

PMID- 24023816
TI  - Trends in child immunization across geographical regions in India: focus on urban
      rural and gender differentials.
AB  - BACKGROUND: Although child immunization is regarded as a highly cost-effective
      lifesaver, about fifty percent of the eligible children aged 12-23 months in
      India are without essential immunization coverage. Despite several programmatic
      initiatives, urban-rural and gender difference in child immunization pose an
      intimidating challenge to India's public health agenda. This study assesses the
      urban-rural and gender difference in child immunization coverage during 1992-2006
      across six major geographical regions in India. DATA AND METHODS: Three rounds of
      the National Family Health Survey (NFHS) conducted during 1992-93, 1998-99 and
      2005-06 were analyzed. Bivariate analyses, urban-rural and gender inequality
      ratios, and the multivariate-pooled logistic regression model were applied to
      examine the trends and patterns of inequalities over time. KEY FINDINGS: The
      analysis of change over one and half decades (1992-2006) shows considerable
      variations in child immunization coverage across six geographical regions in
      India. Despite a decline in urban-rural and gender differences over time,
      children residing in rural areas and girls remained disadvantaged. Moreover,
      northeast, west and south regions, which had the lowest gender inequality in 1992
      observed an increase in gender difference over time. Similarly, urban-rural
      inequality increased in the west region during 1992-2006. CONCLUSION: This study
      suggests periodic evaluation of the health care system is vital to assess the
      between and within group difference beyond average improvement. It is essential
      to integrate strong immunization systems with broad health systems and coordinate
      with other primary health care delivery programs to augment immunization
      coverage.

PMID- 24023817
TI  - The -160C>a polymorphism in E-cadherin is associated with the risk of
      nephrolithiasis.
AB  - Nephrolithiasis is a common disorder worldwide. E-cadherin (CDH1) is involved in
      epithelial cell-cell interactions and plays important roles in the etiology of
      nephrolithiasis. We hypothesized that variants in the CDH1 gene are associated
      with risk of nephrolithiasis. In a hospital-based case-control study of 127
      nephrolithiasis patients and 152 controls frequency matched by age and sex, we
      genotyped the functional -160C>A (rs16260) polymorphism and assessed its
      associations with risk of nephrolithiasis in a Chinese population. We found that
      the CA/AA genotypes were associated with a significantly decreased risk of
      nephrolithiasis (OR = 0.53, 95%CI = 0.32-0.87), compared with the CC genotype,
      particularly among subgroups of BMI > 24 kg/m(2) (OR = 0.38, 95%CI = 0.17-0.85),
      age <= 57 years (OR = 0.47, 95%CI = 0.24-0.93), and men (OR = 0.56, 95%CI = 0.29
      0.99). Our results suggest that the CDH1 polymorphism is involved in the etiology
      of nephrolithiasis and thus may be a marker for genetic susceptibility to
      nephrolithiasis. 

PMID- 24023818
TI  - Rapid and continuous modulation of hippocampal network state during exploration
      of new places.
AB  - Hippocampal information processing is often described as two-state, with a place
      cell state during movement and a reactivation state during stillness. Relatively
      little is known about how the network transitions between these different
      patterns of activity during exploration. Here we show that hippocampal network
      changes quickly and continuously as animals explore and become familiar with
      initially novel places. We measured the relationship between moment-by-moment
      changes in behavior and information flow through hippocampal output area CA1 in
      rats. We examined local field potential (LFP) patterns, evoked potentials and
      ensemble spiking and found evidence suggestive of a smooth transition from strong
      CA3 drive of CA1 activity at low speeds to entorhinal cortical drive of CA1
      activity at higher speeds. These changes occurred with changes in behavior on a
      timescale of less than a second, suggesting a continuous modulation of
      information processing in the hippocampal circuit as a function of behavioral
      state. 

PMID- 24023819
TI  - Nef-specific CD8+ T cell responses contribute to HIV-1 immune control.
AB  - Recent studies in the SIV-macaque model of HIV infection suggest that Nef
      specific CD8+ T-cell responses may mediate highly effective immune control of
      viraemia. In HIV infection Nef recognition dominates in acute infection, but in
      large cohort studies of chronically infected subjects, breadth of T cell
      responses to Nef has not been correlated with significant viraemic control.
      Improved disease outcomes have instead been associated with targeting Gag and, in
      some cases, Pol. However analyses of the breadth of Nef-specific T cell responses
      have been confounded by the extreme immunogenicity and multiple epitope overlap
      within the central regions of Nef, making discrimination of distinct responses
      impossible via IFN-gamma ELISPOT assays. Thus an alternative approach to assess
      Nef as an immune target is needed. Here, we show in a cohort of >700 individuals
      with chronic C-clade infection that >50% of HLA-B-selected polymorphisms within
      Nef are associated with a predicted fitness cost to the virus, and that HLA-B
      alleles that successfully drive selection within Nef are those linked with lower
      viral loads. Furthermore, the specific CD8+ T cell epitopes that are restricted
      by protective HLA Class I alleles correspond substantially to effective SIV
      specific epitopes in Nef. Distinguishing such individual HIV-specific responses
      within Nef requires specific peptide-MHC I tetramers. Overall, these data suggest
      that CD8+ T cell targeting of certain specific Nef epitopes contributes to HIV
      suppression. These data suggest that a re-evaluation of the potential use of Nef
      in HIV T-cell vaccine candidates would be justified. 

PMID- 24023820
TI  - N-octanoyl dopamine inhibits the expression of a subset of kappaB regulated
      genes: potential role of p65 Ser276 phosphorylation.
AB  - BACKGROUND AND PURPOSE: Catechol containing compounds have anti-inflammatory
      properties, yet for catecholamines these properties are modest. Since we have
      previously demonstrated that the synthetic dopamine derivative N-octanoyl
      dopamine (NOD) has superior anti-inflammatory properties compared to dopamine, we
      tested NOD in more detail and sought to elucidate the molecular entities and
      underlying mechanism by which NOD down-regulates inflammation. EXPERIMENTAL
      APPROACH: Genome wide gene expression profiling of human umbilical vein
      endothelial cells (HUVECs) was performed after stimulation with TNF-alpha or in
      the combination with NOD. Confirmation of these differences, NFkappaB activation
      and the molecular entities that were required for the anti-inflammatory
      properties were assessed in subsequent experiments. KEY RESULTS: Down regulation
      of inflammatory genes by NOD occurred predominantly for kappaB regulated genes,
      however not all kappaB regulated genes were affected. These findings were
      explained by inhibition of RelA phosphorylation at Ser276. Leukocyte adherence to
      TNF-alpha stimulated HUVECs was inhibited by NOD and was reflected by a
      diminished expression of adhesion molecules on HUVECs. NOD induced HO-1
      expression, but this was not required for inhibition of NFkappaB. The anti
      inflammatory effect of NOD seems to involve the redox active catechol structure,
      although the redox active para-dihydroxy benzene containing compounds also
      displayed anti-inflammatory effects, provided that they were sufficiently
      hydrophobic. CONCLUSIONS AND IMPLICATIONS: The present study highlighted
      important mechanisms and molecular entities by which dihydroxy benzene compounds
      exert their potential anti-inflammatory action. Since NOD does not have
      hemodynamic properties, NOD seems to be a promising candidate drug for the
      treatment of inflammatory diseases.

PMID- 24023821
TI  - Directed evolution of Mycobacterium tuberculosis beta-lactamase reveals
      gatekeeper residue that regulates antibiotic resistance and catalytic efficiency.
AB  - Directed evolution can be a powerful tool for revealing the mutational pathways
      that lead to more resistant bacterial strains. In this study, we focused on the
      bacterium Mycobacterium tuberculosis, which is resistant to members of the beta
      lactam class of antibiotics and thus continues to pose a major public health
      threat. Resistance of this organism is the result of a chromosomally encoded,
      extended spectrum class A beta-lactamase, BlaC, that is constitutively produced.
      Here, combinatorial enzyme libraries were selected on ampicillin to identify
      mutations that increased resistance of bacteria to beta-lactams. After just a
      single round of mutagenesis and selection, BlaC mutants were evolved that
      conferred 5-fold greater antibiotic resistance to cells and enhanced the
      catalytic efficiency of BlaC by 3-fold compared to the wild-type enzyme. All
      isolated mutants carried a mutation at position 105 (e.g., I105F) that appears to
      widen access to the active site by 3.6 A while also stabilizing the reorganized
      topology. In light of these findings, we propose that I105 is a 'gatekeeper'
      residue of the active site that regulates substrate hydrolysis by BlaC. Moreover,
      our results suggest that directed evolution can provide insight into the
      development of highly drug resistant microorganisms. 

PMID- 24023822
TI  - Feasibility study of a wearable exoskeleton for children: is the gait altered by
      adding masses on lower limbs?
AB  - We are designing a pediatric exoskeletal ankle robot (pediatric Anklebot) to
      promote gait habilitation in children with Cerebral Palsy (CP). Few studies have
      evaluated how much or whether the unilateral loading of a wearable exoskeleton
      may have the unwanted effect of altering significantly the gait. The purpose of
      this study was to evaluate whether adding masses up to 2.5 kg, the estimated
      overall added mass of the mentioned device, at the knee level alters the gait
      kinematics. Ten healthy children and eight children with CP, with light or mild
      gait impairment, walked wearing a knee brace with several masses. Gait parameters
      and lower-limb joint kinematics were analyzed with an optoelectronic system under
      six conditions: without brace (natural gait) and with masses placed at the knee
      level (0.5, 1.0, 1.5, 2.0, 2.5 kg). T-tests and repeated measures ANOVA tests
      were conducted in order to find noteworthy differences among the trial conditions
      and between loaded and unloaded legs. No statistically significant differences in
      gait parameters for both healthy children and children with CP were observed in
      the five "with added mass" conditions. We found significant differences among
      "natural gait" and "with added masses" conditions in knee flexion and hip
      extension angles for healthy children and in knee flexion angle for children with
      CP. This result can be interpreted as an effect of the mechanical constraint
      induced by the knee brace rather than the effect associated with load increase.
      The study demonstrates that the mechanical constraint induced by the brace has a
      measurable effect on the gait of healthy children and children with CP and that
      the added mass up to 2.5 kg does not alter the lower limb kinematics. This
      suggests that wearable devices weighing 25 N or less will not noticeably modify
      the gait patterns of the population examined here. 

PMID- 24023823
TI  - Seeing is believing: neural representations of visual stimuli in human auditory
      cortex correlate with illusory auditory perceptions.
AB  - In interpersonal communication, the listener can often see as well as hear the
      speaker. Visual stimuli can subtly change a listener's auditory perception, as in
      the McGurk illusion, in which perception of a phoneme's auditory identity is
      changed by a concurrent video of a mouth articulating a different phoneme.
      Studies have yet to link visual influences on the neural representation of
      language with subjective language perception. Here we show that vision influences
      the electrophysiological representation of phonemes in human auditory cortex
      prior to the presentation of the auditory stimulus. We used the McGurk effect to
      dissociate the subjective perception of phonemes from the auditory stimuli. With
      this paradigm we demonstrate that neural representations in auditory cortex are
      more closely correlated with the visual stimuli of mouth articulation, which
      drive the illusory subjective auditory perception, than the actual auditory
      stimuli. Additionally, information about visual and auditory stimuli transfer in
      the caudal-rostral direction along the superior temporal gyrus during phoneme
      perception as would be expected of visual information flowing from the occipital
      cortex into the ventral auditory processing stream. These results show that
      visual stimuli influence the neural representation in auditory cortex early in
      sensory processing and may override the subjective auditory perceptions normally
      generated by auditory stimuli. These findings depict a marked influence of vision
      on the neural processing of audition in tertiary auditory cortex and suggest a
      mechanistic underpinning for the McGurk effect. 

PMID- 24023824
TI  - Propolis augments apoptosis induced by butyrate via targeting cell survival
      pathways.
AB  - Diet is one of the major lifestyle factors affecting incidence of colorectal
      cancer (CC), and despite accumulating evidence that numerous diet-derived
      compounds modulate CC incidence, definitive dietary recommendations are not
      available. We propose a strategy that could facilitate the design of dietary
      supplements with CC-preventive properties. Thus, nutrient combinations that are a
      source of apoptosis-inducers and inhibitors of compensatory cell proliferation
      pathways (e.g., AKT signaling) may produce high levels of programmed death in CC
      cells. Here we report the combined effect of butyrate, an apoptosis inducer that
      is produced through fermentation of fiber in the colon, and propolis, a honeybee
      product, on CC cells. We established that propolis increases the apoptosis of CC
      cells exposed to butyrate through suppression of cell survival pathways such as
      the AKT signaling. The programmed death of CC cells by combined exposure to
      butyrate and propolis is further augmented by inhibition of the JNK signaling
      pathway. Analyses on the contribution of the downstream targets of JNK signaling,
      c-JUN and JAK/STAT, to the apoptosis of butyrate/propolis-treated CC cells
      ascertained that JAK/STAT signaling has an anti-apoptotic role; whereas, the role
      of cJUN might be dependent upon regulatory cell factors. Thus, our studies
      ascertained that propolis augments apoptosis of butyrate-sensitive CC cells and
      re-sensitizes butyrate-resistant CC cells to apoptosis by suppressing AKT
      signaling and downregulating the JAK/STAT pathway. Future in vivo studies should
      evaluate the CC-preventive potential of a dietary supplement that produces high
      levels of colonic butyrate, propolis, and diet-derived JAK/STAT inhibitors. 

PMID- 24023825
TI  - Gait detection in children with and without hemiplegia using single-axis wearable
      gyroscopes.
AB  - In this work, we develop a novel gait phase detection algorithm based on a hidden
      Markov model, which uses data from foot-mounted single-axis gyroscopes as input.
      We explore whether the proposed gait detection algorithm can generate equivalent
      results as a reference signal provided by force sensitive resistors (FSRs) for
      typically developing children (TD) and children with hemiplegia (HC). We find
      that the algorithm faithfully reproduces reference results in terms of high
      values of sensitivity and specificity with respect to FSR signals. In addition,
      the algorithm distinguishes between TD and HC and is able to assess the level of
      gait ability in patients. Finally, we show that the algorithm can be adapted to
      enable real-time processing with high accuracy. Due to the small, inexpensive
      nature of gyroscopes utilized in this study and the ease of implementation of the
      developed algorithm, this work finds application in the on-going development of
      active orthoses designed for therapy and locomotion in children with gait
      pathologies. 

PMID- 24023826
TI  - Transcription of Tnfaip3 is regulated by NF-kappaB and p38 via C/EBPbeta in
      activated macrophages.
AB  - Macrophages play a pivotal role in the immune system through recognition and
      elimination of microbial pathogens. Toll-like receptors (TLRs) on macrophages
      interact with microbial substances and initiate signal transduction through
      intracellular adapters. TLR4, which recognizes the lipopolysaccharides (LPS) on
      Gram-positive and Gram-negative bacteria, triggers downstream signaling mediators
      and eventually activates IkappaB kinase (IKK) complex and mitogen-activated
      protein kinases (MAPKs) such as p38. Previous reports revealed that, in addition
      to NF-kappaB, a core transcription factor of the innate immune response, the
      induction of some LPS-induced genes in macrophages required another transcription
      factor whose activity depends on p38. However, these additional transcription
      factors remain to be identified. In order to identify p38-activated transcription
      factors that cooperate with NF-kappaB in response to LPS stimulation, microarrays
      were used to identify genes regulated by both NF-kappaB and p38 using wild-type,
      IKK-depleted, and p38 inhibitor-treated mouse bone marrow-derived macrophages
      (BMDMs). In silico analysis of transcription factor binding sites was used to
      predict the potential synergistic transcription factors from the co-expressed
      genes. Among these genes, NF-kappaB and C/EBPbeta, a p38 downstream transcription
      factor, were predicted to co-regulate genes in LPS-stimulated BMDMs. Based on the
      subsequent results of a chromatin immunoprecipitation assay and TNFAIP3
      expression in C/EBPbeta-ablated macrophages, we demonstrated that Tnfaip3 is
      regulated by both NF-kappaB and p38-dependent C/EBPbeta. These results identify a
      novel regulatory mechanism in TLR4-mediated innate immunity. 

PMID- 24023827
TI  - Matrix production and organization by endothelial colony forming cells in
      mechanically strained engineered tissue constructs.
AB  - AIMS: Tissue engineering is an innovative method to restore cardiovascular tissue
      function by implanting either an in vitro cultured tissue or a degradable,
      mechanically functional scaffold that gradually transforms into a living neo
      tissue by recruiting tissue forming cells at the site of implantation.
      Circulating endothelial colony forming cells (ECFCs) are capable of
      differentiating into endothelial cells as well as a mesenchymal ECM-producing
      phenotype, undergoing Endothelial-to-Mesenchymal-transition (EndoMT). We
      investigated the potential of ECFCs to produce and organize ECM under the
      influence of static and cyclic mechanical strain, as well as stimulation with
      transforming growth factor beta1 (TGFbeta1). METHODS AND RESULTS: A fibrin-based
      3D tissue model was used to simulate neo-tissue formation. Extracellular matrix
      organization was monitored using confocal laser-scanning microscopy. ECFCs
      produced collagen and also elastin, but did not form an organized matrix, except
      when cultured with TGFbeta1 under static strain. Here, collagen was aligned more
      parallel to the strain direction, similar to Human Vena Saphena Cell-seeded
      controls. Priming ECFC with TGFbeta1 before exposing them to strain led to more
      homogenous matrix production. CONCLUSIONS: Biochemical and mechanical cues can
      induce extracellular matrix formation by ECFCs in tissue models that mimic early
      tissue formation. Our findings suggest that priming with bioactives may be
      required to optimize neo-tissue development with ECFCs and has important
      consequences for the timing of stimuli applied to scaffold designs for both in
      vitro and in situ cardiovascular tissue engineering. The results obtained with
      ECFCs differ from those obtained with other cell sources, such as vena saphena
      derived myofibroblasts, underlining the need for experimental models like ours to
      test novel cell sources for cardiovascular tissue engineering.

PMID- 24023829
TI  - Embedding synthetic microvascular networks in poly(lactic acid) substrates with
      rounded cross-sections for cell culture applications.
AB  - Synthetic microvascular networks are essential to enable in vitro studies of cell
      biology, biophysics, hemodynamics, and drug discovery, as well as in applications
      involving tissue engineering and artificial vasculature. But current limitations
      make it challenging to construct networks incorporating a hierarchy of
      microchannel diameters that possess cell-favored circular cross-sectional
      topographies. We report a new approach that overcomes these limitations by
      employing pressure-assisted expansion of biocompatible degradable poly(lactic
      acid) (PLA) substrates. This single-step process is straightforward and highly
      controllable, making it possible to simultaneously shape the interior topology of
      branched 3D and pseudo-3D microchannel networks across wide range of diameters.
      We further demonstrate in vitro culture of confluent endothelial cell monolayers
      in microchannel networks treated by this process, suggesting potential as a tool
      to help generate bio-mimicking vascular-like environments. 

PMID- 24023828
TI  - Prevalence and perceived preventability of self-reported adverse drug events--a
      population-based survey of 7099 adults.
AB  - PURPOSE: Adverse drug events (ADEs) are common and often preventable among
      inpatients, but self-reported ADEs have not been investigated in a representative
      sample of the general public. The objectives of this study were to estimate the 1
      month prevalence of self-reported ADEs among the adult general public, and the
      perceived preventability of 2 ADE categories: adverse drug reactions (ADRs) and
      sub-therapeutic effects (STEs). METHODS: In this cross-sectional study, a postal
      survey was sent in October 2010 to a random sample of 13 931 Swedish residents
      aged >= 18 years. Self-reported ADEs experienced during the past month included
      ADRs, STEs, drug dependence, drug intoxications and morbidity due to drug-related
      untreated indication. ADEs could be associated with prescription, non
      prescription or herbal drugs. The respondents estimated whether ADRs and STEs
      could have been prevented. ADE prevalences in age groups (18-44, 45-64, or >=65
      years) were compared. RESULTS: Of 7099 respondents (response rate 51.0%), ADEs
      were reported by 19.4% (95% confidence interval, 18.5-20.3%), and the prevalence
      did not differ by age group (p>0.05). The prevalences of self-reported ADRs,
      STEs, and morbidities due to drug-related untreated indications were 7.8% (7.2
      8.4%), 7.6% (7.0-8.2%) and 8.1% (7.5-8.7%), respectively. The prevalence of self
      reported drug dependence was 2.2% (1.9-2.6%), and drug intoxications 0.2% (0.1
      0.3%). The respondents considered 19.2% (14.8-23.6%) of ADRs and STEs
      preventable. Although reported drugs varied between ADE categories, most ADEs
      were attributable to commonly dispensed drugs. Drugs reported for all and
      preventable events were similar. CONCLUSIONS: One-fifth of the adult general
      public across age groups reported ADEs during the past month, indicating a need
      for prevention strategies beyond hospitalised patients. For this, the underlying
      causes of ADEs should increasingly be investigated. The high burden of ADEs and
      preventable ADEs from widely used drugs across care settings supports redesigning
      a safer healthcare system to adequately tackle the problem.

PMID- 24023830
TI  - Phenotypic variation in the plant pathogenic bacterium Acidovorax citrulli.
AB  - Acidovorax citrulli causes bacterial fruit blotch (BFB) of cucurbits, a disease
      that threatens the cucurbit industry worldwide. Despite the economic importance
      of BFB, little is known about pathogenicity and fitness strategies of the
      bacterium. We have observed the phenomenon of phenotypic variation in A.
      citrulli. Here we report the characterization of phenotypic variants (PVs) of two
      strains, M6 and 7a1, isolated from melon and watermelon, respectively. Phenotypic
      variation was observed following growth in rich medium, as well as upon isolation
      of bacteria from inoculated plants or exposure to several stresses, including
      heat, salt and acidic conditions. When grown on nutrient agar, all PV colonies
      possessed a translucent appearance, in contrast to parental strain colonies that
      were opaque. After 72 h, PV colonies were bigger than parental colonies, and had
      a fuzzy appearance relative to parental strain colonies that are relatively
      smooth. A. citrulli colonies are generally surrounded by haloes detectable by the
      naked eye. These haloes are formed by type IV pilus (T4P)-mediated twitching
      motility that occurs at the edge of the colony. No twitching haloes could be
      detected around colonies of both M6 and 7a1 PVs, and microscopy observations
      confirmed that indeed the PVs did not perform twitching motility. In agreement
      with these results, transmission electron microscopy revealed that M6 and 7a1 PVs
      do not produce T4P under tested conditions. PVs also differed from their parental
      strain in swimming motility and biofilm formation, and interestingly, all
      assessed variants were less virulent than their corresponding parental strains in
      seed transmission assays. Slight alterations could be detected in some DNA
      fingerprinting profiles of 7a1 variants relative to the parental strain, while no
      differences at all could be seen among M6 variants and parental strain,
      suggesting that, at least in the latter, phenotypic variation is mediated by
      slight genetic and/or epigenetic alterations. 

PMID- 24023831
TI  - Heat shock transcriptional responses in an MC-Producing Cyanobacterium
      (Planktothrix agardhii) and its MC-deficient mutant under high light conditions.
AB  - Microcystins (MCs) are the most commonly-reported hepatotoxins produced by
      various cyanobacterial taxa in fresh waters to constitute a potential threat to
      human and animal health. The biological role of MCs in the producer organisms is
      not known, and it would be very useful to understand the driving force behind the
      toxin production. Recent studies have suggested that MCs may have a protective
      function in cells facing environmental stress. Following this starting premise,
      we speculate that under adverse conditions the expression of stress-related genes
      coding for Heat Shock Proteins (Hsp) might be different in an MC-producing strain
      and its MC-deficient mutant. We therefore used RT-qPCR to compare the expression
      of 13 hsp genes of an MC-producing strain of Planktothrix agardhii (CYA126/8) and
      its MC-deficient DeltamcyD mutant over different periods of exposure to high
      light stress (HL). Three reference genes (RGs) were selected from six candidates
      to normalize the RT-qPCR data. Of these three RGs (rsh, rpoD, and gltA), gltA is
      used here for the first time as an RG in prokaryotes. Under HL stress, five genes
      were found to be strongly up-regulated in both strains (htpG, dnaK, hspA, groES,
      and groEL). Unexpectedly, we found that the MC-producing wild type strain
      accumulated higher levels of htpG and dnaK transcripts in response to HL stress
      than the MC-deficient mutant. In addition, a significant increase in the mcyE
      transcript was detected in the mutant, suggesting that MCs are required under HL
      conditions. We discuss several possible roles of MCs in the response to HL stress
      through their possible involvement in the protective mechanisms of the cells. 

PMID- 24023832
TI  - C-Fos regulation by the MAPK and PKC pathways in intervertebral disc cells.
AB  - BACKGROUND: The gene encoding c-fos is an important factor in the pathogenesis of
      joint disease in patients with osteoarthritis. However, it is unknown whether the
      signal mechanism of c-fos acts in intervertebral disc (IVD) cells. We
      investigated whether c-fos is activated in relation to mitogen-activated protein
      kinases (MAPKs) and the protein kinase C (PKC) pathway in nucleus pulposus (NP)
      cells. METHODOLOGY/RESULTS: Reverse transcription-polymerase chain reaction and
      western blotting analyses were used to measure the expression of c-fos in rat IVD
      cells. Transfections were performed to determine the effects of c-fos on target
      gene activity. The effect of c-fos protein expression was examined in
      transfection experiments and in a 3- (4,5-dimethylthiazol-2-yl) -2,5
      diphenyltetrazolium bromide cell viability assay. Phorbol 12-myristate 13-acetate
      (PMA), the most commonly used phorbol ester, binds to and activates protein
      kinase C (PKC), causing a wide range of effects in cells and tissues. PMA induced
      the expression of c-fos gene transcription and protein expression, and led to
      activation of the MAPK pathways in NP cells. The c-fos promoter was suppressed
      completely in the presence of the MAPK inhibitor PD98059, an inhibitor of the
      MEK/ERK kinase cascade, but not in the presence of SKF86002, SB202190, or
      SP600125. The effects of the PKC pathway on the transcriptional activity of the c
      fos were evaluated. PKCgamma and PKCdelta suppressed the promoter activity of c
      fos. Treatment with c-fos inhibited aggrecan and Col2 promoter activities and the
      expression of these genes in NP cells. CONCLUSIONS: This study demonstrated, for
      the first time, that the MAPK and PKC pathways had opposing effects on the
      regulation of c-fos in NP cells. Thus, the expression of c-fos can be suppressed
      in the extracellular matrix of NP cells.

PMID- 24023833
TI  - Development of Agrobacterium-mediated virus-induced gene silencing and
      performance evaluation of four marker genes in Gossypium barbadense.
AB  - Gossypiumbarbadense is a cultivated cotton species and possesses many desirable
      traits, including high fiber quality and resistance to pathogens, especially
      Verticilliumdahliae (a devastating pathogen of Gossypium hirsutum, the main
      cultivated species). These elite traits are difficult to be introduced into G.
      hirsutum through classical breeding methods. In addition, genetic transformation
      of G. barbadense has not been successfully performed. It is therefore important
      to develop methods for evaluating the function and molecular mechanism of genes
      in G. barbadense. In this study, we had successfully introduced a virus-induced
      gene silencing (VIGS) system into three cultivars of G. barbadense by inserting
      marker genes into the tobacco rattle virus (TRV) vector. After we optimized the
      VIGS conditions, including light intensity, photoperiod, seedling age and
      Agrobacterium strain, 100% of plants agroinfiltrated with the GaPDS silencing
      vector showed white colored leaves. Three other marker genes, GaCLA1, GaANS and
      GaANR, were employed to further test this VIGS system in G. barbadense. The
      transcript levels of the endogenous genes in the silenced plants were reduced by
      more than 99% compared to control plants; these plants presented phenotypic
      symptoms 2 weeks after inoculation. We introduced a fusing sequence fragment of
      GaPDS and GaANR gene silencing vectors into a single plant, which resulted in
      both photobleaching and brownish coloration. The extent of silencing in plants
      agroinfiltrated with fusing two-gene-silencing vector was consistent with plants
      harboring a single gene silencing vector. The development of this VIGS system
      should promote analysis of gene function in G. barbadense, and help to contribute
      desirable traits for breeding of G. barbadense and G. hirsutum. 

PMID- 24023835
TI  - A mechanism for value-sensitive decision-making.
AB  - We present a dynamical systems analysis of a decision-making mechanism inspired
      by collective choice in house-hunting honeybee swarms, revealing the crucial role
      of cross-inhibitory 'stop-signalling' in improving the decision-making
      capabilities. We show that strength of cross-inhibition is a decision-parameter
      influencing how decisions depend both on the difference in value and on the mean
      value of the alternatives; this is in contrast to many previous mechanistic
      models of decision-making, which are typically sensitive to decision accuracy
      rather than the value of the option chosen. The strength of cross-inhibition
      determines when deadlock over similarly valued alternatives is maintained or
      broken, as a function of the mean value; thus, changes in cross-inhibition
      strength allow adaptive time-dependent decision-making strategies. Cross
      inhibition also tunes the minimum difference between alternatives required for
      reliable discrimination, in a manner similar to Weber's law of just-noticeable
      difference. Finally, cross-inhibition tunes the speed-accuracy trade-off realised
      when differences in the values of the alternatives are sufficiently large to
      matter. We propose that the model, and the significant role of the values of the
      alternatives, may describe other decision-making systems, including intracellular
      regulatory circuits, and simple neural circuits, and may provide guidance in the
      design of decision-making algorithms for artificial systems, particularly those
      functioning without centralised control. 

PMID- 24023834
TI  - COX-2-765G>C polymorphism increases the risk of cancer: a meta-analysis.
AB  - BACKGROUND: Chronic inflammation has been regarded as an important mechanism in
      carcinogenesis. Inflammation-associated genetic variants have been highly
      associated with cancer risk. Polymorphisms in the gene cyclooxygenase-2 (COX-2),
      a pro-inflammation factor, have been suggested to alter the risk of multiple
      tumors, but the findings of various studies are not consistent. METHODS: A
      literature search through February 2013 was performed using PubMed, EMBASE, and
      CNKI databases. We used odds ratios (ORs) with confidence intervals (CIs) of 95%
      to assess the strength of the association between the COX-2-765G>C polymorphism
      and cancer risk in a random-effect model. We also assessed heterogeneity and
      publication bias. RESULTS: In total, 65 articles with 29,487 cancer cases and
      39,212 non-cancer controls were included in this meta-analysis. The pooled OR
      (95% CIs) in the co-dominant model (GC vs. GG) was 1.11 (1.02-1.22), and in the
      dominant model ((CC+GC) vs. GG), the pooled OR was 1.12 (1.02-1.23). In the
      subgroup analysis, stratified by cancer type and race, significant associations
      were found between the-765 C allele and higher risk for gastric cancer, leukemia,
      pancreatic cancer, and cancer in the Asian population. CONCLUSION: In summary,
      the COX-2-765 C allele was related to increased cancer susceptibility, especially
      gastric cancer and cancer in the Asian population.

PMID- 24023836
TI  - The number of resected lymph nodes (nLNs) combined with tumor size as a
      prognostic factor in patients with pathologic N0 and Nx non-small cell lung
      cancer.
AB  - BACKGROUND: The prognostic role of the number of resected lymph nodes (nLNs) in
      pathologic N0 (lymph node negative) and Nx (no lymph node examined) non-small
      cell lung cancer (NSCLC) patients remains uncertain. Guidelines for optimal nLNs
      have not been established. In the current study, we evaluated whether a higher
      number of resected lymph nodes (LNs) results in better survival in different
      tumor size categories among NSCLC patients without metastatic LNs. METHOD: A
      retrospective study was conducted. Based on nLNs (LN = 0, 1-7, >7) and tumor size
      (Ta: <= 3.5 cm, Tb: >3.5 cm) during surgery, patients were categorized into 6
      groups (LN0Ta, LN0Tb, LN1-7Ta, LN1-7Tb, LN7-Ta and LN7-Tb). Survival and
      multivariate analyses were carried out to determine whether nLNs combined with
      tumor size was significant for overall survival (OS) or disease free survival
      (DFS) after adjusting for potential confounders. RESULTS: A total of 428 patients
      were enrolled in the study. Multivariate analysis demonstrated that nLNs, tumor
      size and pathological stage were the independent prognosticators for OS and DFS.
      Data from our study suggested that lung cancer lymphadenectomy with more than 7
      LNs removed should be considered a benchmark for surgery or pathology at an early
      stage. Survival was significantly better in the LN7-Ta group, compared with other
      5 groups (p<0.001). CONCLUSIONS: The combined predictor (nLNs combined with tumor
      size) is an independent prognostic factor and a reasonable stratification
      criterion in patients with pathologic N0 and Nx NSCLC. The validation of our
      finding is warranted in further investigation.

PMID- 24023837
TI  - Functional outcome, revision rates and mortality after primary total hip
      replacement--a national comparison of nine prosthesis brands in England.
AB  - BACKGROUND: The number of prosthesis brands used for hip replacement has
      increased rapidly, but there is little evidence on their effectiveness. We
      compared patient-reported outcomes, revision rates, and mortality for the three
      most frequently used brands within each prosthesis type: cemented (Exeter V40
      Contemporary, Exeter V40 Duration and Exeter V40 Elite Plus Ogee), cementless
      (Corail Pinnacle, Accolade Trident, and Taperloc Exceed), and hybrid (Exeter V40
      Trilogy, Exeter V40 Trilogy, and CPT Trilogy). METHODS AND FINDINGS: We used
      three national databases of patients who had hip replacements between 2008 and
      2011 in the English NHS to compare functional outcome (Oxford Hip Score (OHS)
      ranging from 0 (worst) to 48 (best)) in 43,524 patients at six months. We
      analysed revisions and mortality in 187,201 patients. We used multiple regression
      to adjust for pre-operative differences. Prosthesis type had an impact on post
      operative OHS and revision rates (both p<0.001). Patients with hybrid prostheses
      had the best functional outcome (mean OHS 39.4, 95%CI 39.1 to 39.7) and those
      with cemented prostheses the worst (37.7, 37.3 to 38.1). Patients with cemented
      prostheses had the lowest reported 5-year revision rates (1.3%, 1.2% to 1.4%) and
      those with cementless prostheses the highest (2.2%, 2.1% to 2.4%). Differences in
      mortality according to prosthesis type were small and not significant (p = 0.06).
      Functional outcome varied according to brand among cemented (p = 0.05, with
      Exeter V40 Duration having the best) and cementless prostheses (p = 0.01, with
      Corail Pinnacle having the best). Revision rates varied according to brand among
      hybrids (p = 0.05, with Exeter V40 Trident having the lowest). CONCLUSIONS:
      Functional outcomes were better with cementless cups and revision rates were
      lower with cemented stems, which underlies the good overall performance of
      hybrids. The hybrid Exeter V40 Trident seemed to produce the best overall
      results. This brand should be considered as a benchmark in randomised trials.

PMID- 24023838
TI  - E1-like activating enzyme Atg7 is preferentially sequestered into p62 aggregates
      via its interaction with LC3-I.
AB  - p62 is constitutively degraded by autophagy via its interaction with LC3.
      However, the interaction of p62 with LC3 species in the context of the LC3
      lipidation process is not specified. Further, the p62-mediated protein
      aggregation's effect on autophagy is unclear. We systemically analyzed the
      interactions of p62 with all known Atg proteins involved in LC3 lipidation. We
      find that p62 does not interact with LC3 at the stages when it is being processed
      by Atg4B or when it is complexed or conjugated with Atg3. p62 does interact with
      LC3-I and LC3-I:Atg7 complex and is preferentially recruited by LC3-II species
      under autophagic stimulation. Given that Atg4B, Atg3 and LC3-Atg3 are
      indispensable for LC3-II conversion, our study reveals a protective mechanism for
      Atg4B, Atg3 and LC3-Atg3 conjugate from being inappropriately sequestered into
      p62 aggregates. Our findings imply that p62 could potentially impair autophagy by
      negatively affecting LC3 lipidation and contribute to the development of protein
      aggregate diseases. 

PMID- 24023840
TI  - Proteasome inhibition promotes Parkin-Ubc13 interaction and lysine 63-linked
      ubiquitination.
AB  - Disruption of the ubiquitin-proteasome system, which normally identifies and
      degrades unwanted intracellular proteins, is thought to underlie
      neurodegeneration. Supporting this, mutations of Parkin, a ubiquitin ligase, are
      associated with autosomal recessive parkinsonism. Remarkably, Parkin can protect
      neurons against a wide spectrum of stress, including those that promote
      proteasome dysfunction. Although the mechanism underlying the preservation of
      proteasome function by Parkin is hitherto unclear, we have previously proposed
      that Parkin-mediated K63-linked ubiquitination (which is usually uncoupled from
      the proteasome) may serve to mitigate proteasomal stress by diverting the
      substrate load away from the machinery. By means of linkage-specific antibodies,
      we demonstrated here that proteasome inhibition indeed promotes K63-linked
      ubiquitination of proteins especially in Parkin-expressing cells. Importantly, we
      further demonstrated that the recruitment of Ubc13 (an E2 that mediates K63
      linked polyubiquitin chain formation exclusively) by Parkin is selectively
      enhanced under conditions of proteasomal stress, thus identifying a mechanism by
      which Parkin could promote K63-linked ubiquitin modification in cells undergoing
      proteolytic stress. This mode of ubiquitination appears to facilitate the
      subsequent clearance of Parkin substrates via autophagy. Consistent with the
      proposed protective role of K63-linked ubiquitination in times of proteolytic
      stress, we found that Ubc13-deficient cells are significantly more susceptible to
      cell death induced by proteasome inhibitors compared to their wild type
      counterparts. Taken together, our study suggests a role for Parkin-mediated K63
      ubiquitination in maintaining cellular protein homeostasis, especially during
      periods when the proteasome is burdened or impaired. 

PMID- 24023839
TI  - A reduce and replace strategy for suppressing vector-borne diseases: insights
      from a deterministic model.
AB  - Genetic approaches for controlling disease vectors have aimed either to reduce
      wild-type populations or to replace wild-type populations with insects that
      cannot transmit pathogens. Here, we propose a Reduce and Replace (R&R) strategy
      in which released insects have both female-killing and anti-pathogen genes. We
      develop a mathematical model to numerically explore release strategies involving
      an R&R strain of the dengue vector Aedes aegypti. We show that repeated R&R
      releases may lead to a temporary decrease in mosquito population density and, in
      the absence of fitness costs associated with the anti-pathogen gene, a long-term
      decrease in competent vector population density. We find that R&R releases more
      rapidly reduce the transient and long-term competent vector densities than female
      killing releases alone. We show that releases including R&R females lead to
      greater reduction in competent vector density than male-only releases. The
      magnitude of reduction in total and competent vectors depends upon the release
      ratio, release duration, and whether females are included in releases. Even when
      the anti-pathogen allele has a fitness cost, R&R releases lead to greater
      reduction in competent vectors than female-killing releases during the release
      period; however, continued releases are needed to maintain low density of
      competent vectors long-term. We discuss the results of the model as motivation
      for more detailed studies of R&R strategies. 

PMID- 24023841
TI  - Preparation of Mn-based selective catalytic reduction catalysts by three methods
      and optimization of process conditions.
AB  - Mn-based catalysts enable high NO x conversion in the selective catalytic
      reduction of NO x with NH3. Three catalyst-production methods, namely, co
      precipitation, impregnation, and sol-gel, were used in this study to determine
      the optimum method and parameters. The maximum catalytic activity was found for
      the catalyst prepared by sol-gel with a 0.5 Mn/Ti ratio. The denitrification
      efficiency using this catalyst was >90%, which was higher than those of catalysts
      prepared by the two other methods. The critical temperature of catalytic activity
      was 353 K. The optimum manganese acetate concentration and weathering time were
      0.10 mol and 24 h, respectively. The gas hourly space velocity and O2
      concentration were determined to be 12000 h(-1) and 3%, respectively.

PMID- 24023842
TI  - Factors secreted by endothelial progenitor cells enhance neurorepair responses
      after cerebral ischemia in mice.
AB  - Cell therapy with endothelial progenitor cells (EPCs) has emerged as a promising
      strategy to regenerate the brain after stroke. Here, we aimed to investigate if
      treatment with EPCs or their secreted factors could potentiate angiogenesis and
      neurogenesis after permanent focal cerebral ischemia in a mouse model of ischemic
      stroke. BALB/C male mice were subjected to distal occlusion of the middle
      cerebral artery, and EPCs, cell-free conditioned media (CM) obtained from EPCs,
      or vehicle media were administered one day after ischemia. Magnetic resonance
      imaging (MRI) was performed at baseline to confirm that the lesions were similar
      between groups. Immunohistochemical and histological evaluation of the brain was
      performed to evaluate angio-neurogenesis and neurological outcome at two weeks.
      CM contained growth factors, such as VEGF, FGF-b and PDGF-bb. A significant
      increase in capillary density was noted in the peri-infarct areas of EPC- and CM
      treated animals. Bielschowsky's staining revealed a significant increase in
      axonal rewiring in EPC-treated animals compared with shams, but not in CM-treated
      mice, in close proximity with DCX-positive migrating neuroblasts. At the
      functional level, post-ischemia forelimb strength was significantly improved in
      animals receiving EPCs or CM, but not in those receiving vehicle media. In
      conclusion, we demonstrate for the first time that the administration of EPC
      secreted factors could become a safe and effective cell-free option to be
      considered in future therapeutic strategies for stroke. 

PMID- 24023843
TI  - Clinical importance of steps taken per day among persons with multiple sclerosis.
AB  - BACKGROUND: The number of steps taken per day (steps/day) provides a reliable and
      valid outcome of free-living walking behavior in persons with multiple sclerosis
      (MS). OBJECTIVE: This study examined the clinical meaningfulness of steps/day
      using the minimal clinically important difference (MCID) value across stages
      representing the developing impact of MS. METHODS: This study was a secondary
      analysis of de-identified data from 15 investigations totaling 786 persons with
      MS and 157 healthy controls. All participants provided demographic information
      and wore an accelerometer or pedometer during the waking hours of a 7-day period.
      Those with MS further provided real-life, health, and clinical information and
      completed the Multiple Sclerosis Walking Scale-12 (MSWS-12) and Patient
      Determined Disease Steps (PDDS) scale. MCID estimates were based on regression
      analyses and analysis of variance for between group differences. RESULTS: The
      mean MCID from self-report scales that capture subtle changes in ambulation (1
      point change in PDSS scores and 10-point change in MSWS-12 scores) was 779
      steps/day (14% of mean score for MS sample); the mean MCID for clinical/health
      outcomes (MS type, duration, weight status) was 1,455 steps/day (26% of mean
      score for MS sample); real-life anchors (unemployment, divorce, assistive device
      use) resulted in a mean MCID of 2,580 steps/day (45% of mean score for MS
      sample); and the MCID for the cumulative impact of MS (MS vs. control) was 2,747
      steps/day (48% of mean score for MS sample). CONCLUSION: The change in motion
      sensor output of ~800 steps/day appears to represent a lower-bound estimate of
      clinically meaningful change in free-living walking behavior in interventions of
      MS.

PMID- 24023844
TI  - Snorkel: an epitope tagging system for measuring the surface expression of
      membrane proteins.
AB  - Tags are widely used to monitor a protein's expression level, interactions,
      protein trafficking, and localization. Membrane proteins are often tagged in
      their extracellular domains to allow discrimination between protein in the plasma
      membrane from that in internal pools. Multipass membrane proteins offer special
      challenges for inserting a tag since the extracellular regions are often composed
      of small loops and thus inserting an epitope tag risks perturbing the structure,
      function, or location of the membrane protein. We have developed a novel tagging
      system called snorkel where a transmembrane domain followed by a tag is appended
      to the cytoplasmic C-terminus of the membrane protein. In this way the tag is
      displayed extracellularly, but structurally separate from the membrane protein.
      We have tested the snorkel tag system on a diverse panel of membrane proteins
      including GPCRs and ion channels and demonstrated that it reliably allows for
      monitoring of the surface expression. 

PMID- 24023845
TI  - Role of diatoms in the spatial-temporal distribution of intracellular nitrate in
      intertidal sediment.
AB  - Intracellular nitrate storage allows microorganisms to survive fluctuating
      nutrient availability and anoxic conditions in aquatic ecosystems. Here we show
      that diatoms, ubiquitous and highly abundant microalgae, represent major cellular
      reservoirs of nitrate in an intertidal flat of the German Wadden Sea and are
      potentially involved in anaerobic nitrate respiration. Intracellular nitrate
      (ICNO3) was present year-round in the sediment and was spatially and temporally
      correlated with fucoxanthin, the marker photopigment of diatoms. Pyrosequencing
      of SSU rRNA genes of all domains of life confirmed that ICNO3 storage was most
      likely due to diatoms rather than other known nitrate-storing microorganisms
      (i.e., large sulfur bacteria and the eukaryotic foraminifers and gromiids).
      Sedimentary ICNO3 concentrations reached up to 22.3 umol dm(-3) at the sediment
      surface and decreased with sediment depth to negligible concentrations below 5
      cm. Similarly, the ICNO3/fucoxanthin ratio and porewater nitrate (PWNO3)
      concentrations decreased with sediment depth, suggesting that ICNO3 of diatoms is
      in equilibrium with PWNO3, but is enriched relative to PWNO3 by 2-3 orders of
      magnitude. Cell-volume-specific ICNO3 concentrations in a diatom mat covering the
      sediment surface during spring were estimated at 9.3-46.7 mmol L(-1). Retrieval
      of 18S rRNA gene sequences related to known nitrate-storing and nitrate
      ammonifying diatom species suggested that diatoms in dark and anoxic sediment
      layers might be involved in anaerobic nitrate respiration. Due to the widespread
      dominance of diatoms in microphytobenthos, the total nitrate pool in coastal
      marine sediments may generally be at least two times larger than derived from
      porewater measurements and partially be recycled to ammonium. 

PMID- 24023846
TI  - Generation and characterization of a diabody targeting the alphavbeta6 integrin.
AB  - The alphavbeta6 integrin is up-regulated in cancer and wound healing but it is
      not generally expressed in healthy adult tissue. There is increasing evidence
      that it has a role in cancer progression and will be a useful target for antibody
      directed cancer therapies. We report a novel recombinant diabody antibody
      fragment that targets specifically alphavbeta6 and blocks its function. The
      diabody was engineered with a C-terminal hexahistidine tag (His tag), expressed
      in Pichia pastoris and purified by IMAC. Surface plasmon resonance (SPR) analysis
      of the purified diabody showed affinity in the nanomolar range. Pre-treatment of
      alphavbeta6-expressing cells with the diabody resulted in a reduction of cell
      migration and adhesion to LAP, demonstrating biological function-blocking
      activity. After radio-labeling, using the His-tag for site-specific attachment of
      (99m)Tc, the diabody retained affinity and targeted specifically to alphavbeta6
      expressing tumors in mice bearing isogenic alphavbeta6 +/- xenografts.
      Furthermore, the diabody was specifically internalized into alphavbeta6
      expressing cells, indicating warhead targeting potential. Our results indicate
      that the new alphavbeta6 diabody has a range of potential applications in
      imaging, function blocking or targeted delivery/internalization of therapeutic
      agents. 

PMID- 24023847
TI  - Expression of Livin in colorectal cancer and its relationship to tumor cell
      behavior and prognosis.
AB  - BACKGROUNDS: Expression of Livin, a member of the inhibitors of apoptosis protein
      family, is associated with tumor development and progression. The aims of this
      study were to evaluate whether Livin affects oncogenic biological behavior of
      colorectal cancer cells, and to document the relationship between its expression
      and various clinicopathological parameters in colorectal cancer. METHODS: We
      investigated the impact of Livin on tumor cell behavior by using the small
      interfering RNA and pcDNA3.1 vector in SW480 and DKO1 colorectal cancer cell
      lines. The expression of Livin was investigated by RT-PCR and
      immunohistochemistry in coloretcal cancer tissues. The apoptotic cells were
      visualized by TUNEL assay, and proliferative cells were visualized by Ki-67
      antibody staining. RESULTS: Knockdown of Livin suppressed tumor cell migration
      and invasion in colorectal cancer cells. Knockdown of Livin induced the apoptosis
      by up-regulating of caspase-3, -7 and PARP activities and the cell cycle arrest
      by decreasing cyclin D1, cyclin D3, cyclin-dependent kinase 4 and 6, and by
      inducing p27 expression. The MAPK signaling cascades were significantly blocked
      by knockdown of Livin. In contrast, overexpression of Livin enhanced tumor cell
      migration and invasion, and inhibited the apoptosis and cell cycle arrest. The
      mean apoptotic index (AI) value of Livin positive tumors was significantly lower
      than AI of Livin negative tumors. However, there was no significant difference
      between Livin expression and Ki-67 labeling index (KI). Livin expression was
      significantly increased in colorectal cancer and metastatic lymph node tissues
      compared to normal colorectal mucosa and non-metastatic lymph node tissues and
      was associated with tumor stage, lymphovascular invasion, lymph node metastasis
      and poor survival. CONCLUSIONS: These results indicate that Livin is associated
      with tumor progression by increasing tumor cell motility and inhibiting apoptosis
      in colorectal cancer.

PMID- 24023848
TI  - Increased microRNA-146a levels in plasma of patients with newly diagnosed type 2
      diabetes mellitus.
AB  - BACKGROUND: MicroRNAs (miRNAs), a class of small non-coding RNAs, are thought to
      serve as crucial regulators of gene expression. Dysregulated expression of miRNAs
      has been described in various diseases and may contribute to related pathologic
      processes. Our aim was to examine circulating miRNA-146a levels in newly
      diagnosed type 2 diabetes mellitus (new-T2DM) patients from a Chinese Han
      population. METHODOLOGY/PRINCIPAL FINDINGS: Circulating miRNA-146a was extracted
      from plasma samples of 90 new-T2DM patients and 90 age- and sex-matched controls.
      Quantitative PCR assessment revealed that circulating miRNA-146a levels were
      significantly elevated in new-T2DM patients compared with controls. Participants
      in the highest tertile of circulating miRNA-146a levels showed a notably higher
      risk for new-T2DM (crude OR 4.333, 95% CI, 1.935 to 9.705, P = 0.001) than
      persons in the lowest tertile. Controlling for known risk factors and some
      biochemical indicators did not attenuate the aforementioned association. In
      addition, receiver operating characteristic (ROC) curves generated for miRNA-146a
      revealed an area under the curve (AUC) of 0.725 (95% CI, 0.651 to 0.799, P <
      0.001). Moreover, higher circulating miRNA-146a levels were significantly
      associated with higher plasma heme oxygenase-1 (HO-1) concentrations (beta
      coefficient = 0.131, P < 0.001) and lower HOMA-beta (beta coefficient = -0.153, P
      = 0.015). CONCLUSIONS/SIGNIFICANCE: We found that circulating miRNA-146a levels
      were significantly elevated in new-T2DM patients compared with healthy controls.
      Whether expression of circulating miRNA-146a holds predictive value for T2DM
      warrants further investigations.

PMID- 24023849
TI  - CD137 facilitates the resolution of acute DSS-induced colonic inflammation in
      mice.
AB  - BACKGROUND: CD137 and its ligand (CD137L) are potent immunoregulatory molecules
      that influence activation, proliferation, differentiation and cell death of
      leukocytes. Expression of CD137 is upregulated in the lamina propria cells of
      Crohn's disease patients. Here, the role of CD137 in acute Dextran-Sodium-Sulfate
      (DSS)-induced colitis in mice was examined. METHODS: We induced acute large bowel
      inflammation (colitis) via DSS administration in CD137(-/-) and wild-type (WT)
      mice. Colitis severity was evaluated by clinical parameters (weight loss),
      cytokine secretion in colon segment cultures, and scoring of histological
      inflammatory parameters. Additionally, populations of lamina propria mononuclear
      cells (LPMNC) and intraepithelial lymphocytes (IEL) were characterized by flow
      cytometry. In a subset of mice, resolution of intestinal inflammation was
      evaluated 3 and 7 days after withdrawal of DSS. RESULTS: We found that both
      CD137(-/-) and WT mice demonstrated a similar degree of inflammation after 5 days
      of DSS exposure. However, the resolution of colonic inflammation was impaired in
      the absence of CD137. This was accompanied by a higher histological score of
      inflammation, and increased release of the pro-inflammatory mediators granulocyte
      macrophage colony-stimulating factor (GM-CSF), CXCL1, IL-17 and IFN-gamma.
      Further, there were significantly more neutrophils among the LPMNC of CD137(-/-)
      mice, and reduced numbers of macrophages among the IEL. CONCLUSION: We conclude
      that CD137 plays an essential role in the resolution of acute DSS-induced
      intestinal inflammation in mice.

PMID- 24023850
TI  - Potential role of microRNA-21 in the diagnosis of gastric cancer: a meta
      analysis.
AB  - INTRODUCTION: Accumulating evidences indicate that microRNA-21(miR-21) show
      significant high concentration in plasma of gastric cancer (GC) patients compared
      to normal individuals, suggesting that it may be a useful novel diagnostic
      biomarker for gastric cancer. Therefore, we aimed to assess the potential
      diagnostic value of miR-21 for gastric cancer in this study. METHODS: Literature
      database including PubMed, Embase, the Cochrane Library, Web of Science, Ovid,
      SciVerse, Science Direct, Scopus, BioMed Central, Biosis previews,Chinese
      Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure
      (CNKI), Technology of Chongqing (VIP), and Wan Fang DATA were searched for
      publications concerning the diagnostic value of miR-21 for GC without language
      restriction. The quality of each study was scored with the Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS). Then, data were retrieved from any
      qualified article hits and subject to meta-analysis. Receiver operating
      characteristic curves (ROC) were used to check the overall test performance.
      Evidence of heterogeneity was evaluated using the Chi-square and I (2) test.
      RESULTS: Five studies with a total 251 GC patients and 184 control individuals
      were included in this meta-analysis. All of the included studies are of high
      quality (QUADAS score$13). The summary estimates revealed that the pooled
      sensitivity is 66.5% (95% confidence interval (CI): 55.0%-76.3%) and the
      specificity is 83.1% (95% CI: 69.4%-91.5%). In addition, the area under the
      summary ROC curve (AUC) is 0.80. CONCLUSION: The current evidence suggests that
      miR-21 has potential diagnostic value with a moderate sensitivity and specificity
      for GC. More prospective studies on the diagnostic value of miR-21 for GC are
      needed in the future.

PMID- 24023851
TI  - Pivotal role of matrix metalloproteinase 13 in extracellular matrix turnover in
      idiopathic pulmonary fibrosis.
AB  - RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized
      by excessive deposition of extracellular matrix (ECM). OBJECTIVES: We
      investigated the regulation of matrix metalloproteinases (MMPs) and their
      inhibitors (TIMPs) in lung fibrosis. METHODS: MMP and TIMP expression,
      collagenolytic activity and collagen content was assessed in IPF (n=16) versus
      donor (n=6) lung homogenates and accomplished by in-situ-zymography for
      gelatinolytic and collagenolytic activities, combined with MMP antigen detection.
      Role of MMP13 was assessed employing the bleomycin model of lung fibrosis in MMP
      13(-/-) versus wild-type mice. MEASUREMENTS AND MAIN RESULTS: In IPF, MMPs-1, 2,
      7, 9 and 13, but not MMP-8, were significantly upregulated, whereas none of the
      TIMPs (1-4) were significantly altered. Collagen content was slightly increased
      and collagenolytic activity was most prominent in the airways and co-localized
      with MMP-13. We observed an exaggerated early inflammatory response and an
      augmented lung fibrosis in bleomycin-challenged MMP-13(-/-) versus wild-type
      mice, with elevated lung collagen content 28d after bleomycin challenge in the
      MMP-13(-/-) mice. CONCLUSIONS: Our data suggest that i) collagen deposition in
      IPF lungs is not primarily due to excessive TIMP production, but rather due to
      overwhelming ECM production in face of an overall increased, but spatially
      imbalanced collagenolytic activity, ii) preferential distribution of
      collagenolytic activity, largely MMP-13, in the airways offers an explanation for
      the development of honeycomb cysts and iii) despite an overall increase in
      inflammatory cell content the presence of MMP-13 seems to limit the overall
      extent of ECM deposition in lung fibrosis.

PMID- 24023852
TI  - On the edge: haptic discrimination of edge sharpness.
AB  - The increasing ubiquity of haptic displays (e.g., smart phones and tablets)
      necessitates a better understanding of the perceptual capabilities of the human
      haptic system. Haptic displays will soon be capable of locally deforming to
      create simple 3D shapes. This study investigated the sensitivity of our haptic
      system to a fundamental component of shapes: edges. A novel set of eight high
      quality shape stimuli with test edges that varied in sharpness were fabricated in
      a 3D printer. In a two alternative, forced choice task, blindfolded participants
      were presented with two of these shapes side by side (one the reference, the
      other selected randomly from the remaining set of seven) and after actively
      exploring the test edge of each shape with the tip of their index finger,
      reported which shape had the sharper edge. We used a model selection approach to
      fit optimal psychometric functions to performance data, and from these obtained
      just noticeable differences and Weber fractions. In Experiment 1, participants
      performed the task with four different references. With sharpness defined as the
      angle at which one surface meets the horizontal plane, the four JNDs closely
      followed Weber's Law, giving a Weber fraction of 0.11. Comparisons to previously
      reported Weber fractions from other haptic manipulations (e.g. amplitude of
      vibration) suggests we are sufficiently sensitive to changes in edge sharpness
      for this to be of potential utility in the design of future haptic displays. In
      Experiment 2, two groups of participants performed the task with a single
      reference but different exploration strategies; one was limited to a single
      touch, the other unconstrained and free to explore as they wished. As predicted,
      the JND in the free exploration condition was lower than that in the single touch
      condition, indicating exploration strategy affects sensitivity to edge sharpness.

PMID- 24023853
TI  - MutS homologue hMSH5: recombinational DSB repair and non-synonymous polymorphic
      variants.
AB  - Double-strand breaks (DSBs) constitute the most deleterious form of DNA lesions
      that can lead to genome alterations and cell death, and the vast majority of DSBs
      arise pathologically in response to DNA damaging agents such as ionizing
      radiation (IR) and chemotherapeutic agents. Recent studies have implicated a role
      for the human MutS homologue hMSH5 in homologous recombination (HR)-mediated DSB
      repair and the DNA damage response. In the present study, we show that hMSH5
      promotes HR-based DSB repair, and this property resides in the carboxyl-terminal
      portion of the protein. Our results demonstrate that DSB-triggered hMSH5
      chromatin association peaks at the proximal regions of the DSB and decreases
      gradually with increased distance from the break. Furthermore, the DSB-triggered
      hMSH5 chromatin association is preceded by and relies on the assembly of hMRE11
      and hRad51 at the proximal regions of the DSB. Lastly, the potential effects of
      hMSH5 non-synonymous variants (L85F, Y202C, V206F, R351G, L377F, and P786S) on HR
      and cell survival in response to DSB-inducing anticancer agents have been
      analyzed. These experiments show that the expression of hMSH5 variants elicits
      different survival responses to anticancer drugs cisplatin, bleomycin,
      doxorubicin and camptothecin. However, the effects of hMSH5 variants on survival
      responses to DSB-inducing agents are not directly correlated to their effects
      exerted on HR-mediated DSB repair, suggesting that the roles of hMSH5 variants in
      the processes of DNA damage response and repair are multifaceted. 

PMID- 24023854
TI  - Multivariate modeling of proteins related to trapezius myalgia, a comparative
      study of female cleaners with or without pain.
AB  - The prevalence of chronic trapezius myalgia is high in women with high exposure
      to awkward working positions, repetitive movements and movements with high
      precision demands. The mechanisms behind chronic trapezius myalgia are not fully
      understood. The purpose of this study was to explore the differences in protein
      content between healthy and myalgic trapezius muscle using proteomics. Muscle
      biopsies from 12 female cleaners with work-related trapezius myalgia and 12 pain
      free female cleaners were obtained from the descending part of the trapezius.
      Proteins were separated with two-dimensional differential gel electrophoresis (2D
      DIGE) and selected proteins were identified with mass spectrometry. In order to
      discriminate the two groups, quantified proteins were fitted to a multivariate
      analysis: partial least square discriminate analysis. The model separated 28
      unique proteins which were related to glycolysis, the tricaboxylic acid cycle, to
      the contractile apparatus, the cytoskeleton and to acute response proteins. The
      results suggest altered metabolism, a higher abundance of proteins related to
      inflammation in myalgic cleaners compared to healthy, and a possible alteration
      of the contractile apparatus. This explorative proteomic screening of proteins
      related to chronic pain in the trapezius muscle provides new important aspects of
      the pathophysiology behind chronic trapezius myalgia. 

PMID- 24023855
TI  - Androgen receptor function links human sexual dimorphism to DNA methylation.
AB  - Sex differences are well known to be determinants of development, health and
      disease. Epigenetic mechanisms are also known to differ between men and women
      through X-inactivation in females. We hypothesized that epigenetic sex
      differences may also result from sex hormone functions, in particular from long
      lasting androgen programming. We aimed at investigating whether inactivation of
      the androgen receptor, the key regulator of normal male sex development, is
      associated with differences of the patterns of DNA methylation marks in genital
      tissues. To this end, we performed large scale array-based analysis of gene
      methylation profiles on genomic DNA from labioscrotal skin fibroblasts of 8 males
      and 26 individuals with androgen insensitivity syndrome (AIS) due to inactivating
      androgen receptor gene mutations. By this approach we identified differential
      methylation of 167 CpG loci representing 162 unique human genes. These were
      significantly enriched for androgen target genes and low CpG content promoter
      genes. Additional 75 genes showed a significant increase of heterogeneity of
      methylation in AIS compared to a high homogeneity in normal male controls. Our
      data show that normal and aberrant androgen receptor function is associated with
      distinct patterns of DNA-methylation marks in genital tissues. These findings
      support the concept that transcription factor binding to the DNA has an impact on
      the shape of the DNA methylome. These data which derived from a rare human model
      suggest that androgen programming of methylation marks contributes to sexual
      dimorphism in the human which might have considerable impact on the manifestation
      of sex-associated phenotypes and diseases. 

PMID- 24023857
TI  - Depression-like behavioral phenotypes by social and social plus visual isolation
      in the adult female Macaca fascicularis.
AB  - Major depressive disorder (MDD) is a debilitating psychiatric mood disorder that
      affects millions of individuals globally. Our understanding of the biological
      basis of MDD is poor, and current treatments are ineffective in a significant
      proportion of cases. This current situation may relate to the dominant rodent
      animal models of depression, which possess translational limitations due to
      limited homologies with humans. Therefore, a more homologous primate model of
      depression is needed to advance investigation into the pathophysiological
      mechanisms underlying depression and to conduct pre-clinical therapeutic trials.
      Here, we report two convenient methods--social isolation and social plus visual
      isolation--which can be applied to construct a non-human primate model of
      depression in the adult female cynomolgus monkey (Macaca fascicularis). Both
      social and social plus visual isolation were shown to be effective in inducing
      depression-like behavior by significantly reducing socially dominant aggressive
      conflict behavior, communicative behavior, sexual behavior, and parental
      behavior. The addition of visual isolation produced more profound behavioral
      changes than social isolation alone by further reducing parental behavior and
      sexual behavior. Thus, the degree of behavioral pathology may be manipulated by
      the degree of isolation. These methods can be applied to construct a non-human
      primate model of depression in order to assess physiological, behavioral, and
      social phenomena in a controlled laboratory setting.

PMID- 24023856
TI  - Analysis of essential Arabidopsis nuclear genes encoding plastid-targeted
      proteins.
AB  - The Chloroplast 2010 Project (http://www.plastid.msu.edu/) identified and
      phenotypically characterized homozygous mutants in over three thousand genes, the
      majority of which encode plastid-targeted proteins. Despite extensive screening
      by the community, no homozygous mutant alleles were available for several hundred
      genes, suggesting that these might be enriched for genes of essential function.
      Attempts were made to generate homozygotes in ~1200 of these lines and 521 of the
      homozygous viable lines obtained were deposited in the Arabidopsis Biological
      Resource Center (http://abrc.osu.edu/). Lines that did not yield a homozygote in
      soil were tested as potentially homozygous lethal due to defects either in seed
      or seedling development. Mutants were characterized at four stages of
      development: developing seed, mature seed, at germination, and developing
      seedlings. To distinguish seed development or seed pigment-defective mutants from
      seedling development mutants, development of seeds was assayed in siliques from
      heterozygous plants. Segregating seeds from heterozygous parents were sown on
      supplemented media in an attempt to rescue homozygous seedlings that could not
      germinate or survive in soil. Growth of segregating seeds in air and air enriched
      to 0.3% carbon dioxide was compared to discover mutants potentially impaired in
      photorespiration or otherwise responsive to CO2 supplementation. Chlorophyll
      fluorescence measurements identified CO2-responsive mutants with altered
      photosynthetic parameters. Examples of genes with a viable mutant allele and one
      or more putative homozygous-lethal alleles were documented. RT-PCR of homozygotes
      for potentially weak alleles revealed that essential genes may remain
      undiscovered because of the lack of a true null mutant allele. This work revealed
      33 genes with two or more lethal alleles and 73 genes whose essentiality was not
      confirmed with an independent lethal mutation, although in some cases second
      leaky alleles were identified.

PMID- 24023858
TI  - Rab11 plays an indispensable role in the differentiation and development of the
      indirect flight muscles in Drosophila.
AB  - Rab11, an evolutionary conserved, ubiquitously expressed subfamily of small
      monomeric GTPase has been known to regulate diverse cellular and developmental
      events, by regulating the exocytotic and transcytotic events inside the cell. Our
      studies show that Rab11 regulates Drosophila adult myogenesis by controlling
      proliferation and differentiation of the Adult muscle precursors (AMPs). Blocking
      Rab11 in the AMPs, which fuse to form the Indirect Flight Muscles (IFMs) of fly,
      renders flies completely flightless and non-viable. The indirect flight
      musculature, comprising of the differentially patterned dorsal longitudinal
      muscles (DLMs) and dorsal ventral muscles (DVMs), is affected to different
      extents. Abrogating or knocking down normal Rab11 function results in severely
      disrupted IFMs. DLMs forming from larval templates are reduced in number along
      with a significant reduction in their fibre size. The de novo developing DVMs are
      frequently absent. The DLMs in Rab11 hypomorphs are highly reduced, showing as a
      small constricted mass in one half of the thorax. Further, Rab11 function is
      essential for growth of these muscles during later half of adult myogenesis, as
      down regulation of Rab11 in IFMs results in degenerated muscles and broken
      fibres. Finally, we show that loss of Rab11 activity in the AMPs result in
      acquisition of migratory characteristic of myoblast as they show cellular
      protrusion at their polar ends accompanied with loss of cell-cell contacts. Our
      data provide the first evidence of a trafficking protein playing an indispensable
      role in regulating early stages of adult muscle development. 

PMID- 24023859
TI  - Hepatic stellate cells secreted hepatocyte growth factor contributes to the
      chemoresistance of hepatocellular carcinoma.
AB  - As the main source of extracellular matrix proteins in tumor stroma, hepatic
      stellate cells (HSCs) have a great impact on biological behaviors of
      hepatocellular carcinoma (HCC). In the present study, we have investigated a
      mechanism whereby HSCs modulate the chemoresistance of hepatoma cells. We used
      human HSC line lx-2 and chemotherapeutic agent cisplatin to investigate their
      effects on human HCC cell line Hep3B. The results showed that cisplatin
      resistance in Hep3B cells was enhanced with LX-2 CM (cultured medium) exposure in
      vitro as well as co-injection with LX-2 cells in null mice. Meanwhile, in
      presence of LX-2 CM, Hep3B cells underwent epithelial to mesenchymal transition
      (EMT) and upregulation of cancer stem cell (CSC) -like properties. Besides, LX-2
      cells synthesized and secreted hepatic growth factor (HGF) into the CM. HGF
      receptor tyrosine kinase mesenchymal-epithelial transition factor (Met) was
      activated in Hep3B cells after LX-2 CM exposure. The HGF level of LX-2 CM could
      be effectively reduced by using HGF neutralizing antibody. Furthermore, depletion
      of HGF in LX-2 CM abolished its effects on activation of Met as well as promotion
      of the EMT, CSC-like features and cisplatin resistance in Hep3B cells.
      Collectively, secreting HGF into tumor milieu, HSCs may decrease hepatoma cells
      sensitization to chemotherapeutic agents by promoting EMT and CSC-like features
      via HGF/Met signaling. 

PMID- 24023860
TI  - Polymorphisms in the MASP1 gene are associated with serum levels of MASP-1, MASP
      3, and MAp44.
AB  - INTRODUCTION: MASP-1 is the first protein in the activation of the lectin pathway
      and MASP-1 is, like its isoforms MASP-3 and MAp44, encoded by the MASP1 gene. Our
      aim was to explore associations between polymorphisms in MASP1 and corresponding
      concentrations of MASP-1, MASP-3, and MAp44 in plasma as well as the genetic
      contribution to the equilibrium between the three proteins. METHODS: Fifteen SNPs
      were genotyped in the MASP1 gene in 350 blood donors. Corresponding plasma
      concentrations of MASP-1, MASP-3, and MAp44 were measured. RESULTS: A total of 10
      different SNPs showed associations with the concentration of one or some of the
      three proteins (rs113938200, rs190590338, rs35089177, rs3774275, rs67143992,
      rs698090, rs72549154, rs72549254, rs75284004, rs7625133), and several of these
      were in strong linkage. SNPs located in the mutually exclusive splice region had
      opposite effects on the protein concentrations. Being e.g. homozygote for the
      minor allele of rs3774275 was associated with an increase in median concentration
      of 13% in MASP-1(P=0.03), 29% in MAp44 (P<0.001), and a decrease in MASP-3 of 26%
      (P<0.001) compared to homozygosis for the major allele. Heterozygosis of
      rs113938200 (p.Asn368Asp in MAp44) was associated with a reduced MAp44
      concentration of 61% (P=0.005). Rs190590338 located in the promoter region was
      associated in the heterozygote form with an increased MASP-1 concentration of 35%
      (P = 0.002). A multivariate linear regression model including sex, age, M- and H
      ficolin, MBL, and the 15 SNPs explained 20-48% of the variation in the
      concentration of the three proteins and the SNPs investigated contributed with
      the most explanatory power (12-23%). DISCUSSION: The present study described 10
      SNPs, which were associated with the concentration of one or some of the three
      proteins originating from the MASP1 gene and in a multivariate model it was shown
      that the SNPs contributed with the most explanatory power to the protein
      concentrations.

PMID- 24023861
TI  - Millisecond, micron precision multi-whisker detector.
AB  - The neural mechanisms of somatosensory information processing in the rodent
      vibrissae system are a topic of intense debate and research. Certain hypotheses
      emphasize the importance of stick-slip whisker motion, high-frequency resonant
      vibrations, and/or the ability to decode complex textures. Other hypotheses focus
      on the importance of integrating information from multiple whiskers. Tests of the
      former require measurements of whisker motion that achieve high spatiotemporal
      accuracy without altering the mechanical properties of whiskers. Tests of the
      latter require the ability to monitor the motion of multiple whiskers
      simultaneously. Here we present a device that achieves both these requirements
      for two-dimensional whisker motion in the plane perpendicular to the whiskers.
      Moreover, the system we present is significantly less expensive (<$2.5 k) and
      simpler to build than alternative devices which achieve similar detection
      capabilities. Our system is based on two laser diodes and two linear cameras. It
      attains millisecond temporal precision and micron spatial resolution. We
      developed automated algorithms for processing the data collected by our device
      and benchmarked their performance against manual detection by human visual
      inspection. By this measure, our detection was successful with less than 10 um
      deviation between the automated and manual detection, on average. Here, we
      demonstrate its utility in anesthetized rats by measuring the motion of multiple
      whiskers in response to an air puff. 

PMID- 24023862
TI  - Hyperoxia decreases glycolytic capacity, glycolytic reserve and oxidative
      phosphorylation in MLE-12 cells and inhibits complex I and II function, but not
      complex IV in isolated mouse lung mitochondria.
AB  - High levels of oxygen (hyperoxia) are frequently used in critical care units and
      in conditions of respiratory insufficiencies in adults, as well as in infants.
      However, hyperoxia has been implicated in a number of pulmonary disorders
      including bronchopulmonary dysplasia (BPD) and adult respiratory distress
      syndrome (ARDS). Hyperoxia increases the generation of reactive oxygen species
      (ROS) in the mitochondria that could impair the function of the mitochondrial
      electron transport chain. We analyzed lung mitochondrial function in hyperoxia
      using the XF24 analyzer (extracellular flux) and optimized the assay for lung
      epithelial cells and mitochondria isolated from lungs of mice. Our data show that
      hyperoxia decreases basal oxygen consumption rate (OCR), spare respiratory
      capacity, maximal respiration and ATP turnover in MLE-12 cells. There was
      significant decrease in glycolytic capacity and glycolytic reserve in MLE-12
      cells exposed to hyperoxia. Using mitochondria isolated from lungs of mice
      exposed to hyperoxia or normoxia we have shown that hyperoxia decreased the
      basal, state 3 and state3 MU (respiration in an uncoupled state) respirations.
      Further, using substrate or inhibitor of a specific complex we show that the OCR
      via complex I and II, but not complex IV was decreased, demonstrating that
      complexes I and II are specific targets of hyperoxia. Further, the activities of
      complex I (NADH dehydrogenase, NADH-DH) and complex II (succinate dehydrogenase,
      SDH) were decreased in hyperoxia, but the activity of complex IV (cytochrome
      oxidase, COX) remains unchanged. Taken together, our study show that hyperoxia
      impairs glycolytic and mitochondrial energy metabolism in in tact cells, as well
      as in lungs of mice by selectively inactivating components of electron transport
      system. 

PMID- 24023863
TI  - Editorial decisions may perpetuate belief in invalid research findings.
AB  - Social psychology and related disciplines are seeing a resurgence of interest in
      replication, as well as actual replication efforts. But prior work suggests that
      even a clear demonstration that a finding is invalid often fails to shake
      acceptance of the finding. This threatens the full impact of these replication
      efforts. Here we show that the actions of two key players--journal editors and
      the authors of original (invalidated) research findings--are critical to the
      broader public's continued belief in an invalidated research conclusion. Across
      three experiments, we show that belief in an invalidated finding falls sharply
      when a critical failed replication is published in the same--versus different-
      journal as the original finding, and when the authors of the original finding
      acknowledge that the new findings invalidate their conclusions. We conclude by
      discussing policy implications of our key findings.

PMID- 24023864
TI  - "Righteous minds" in health care: measurement and explanatory value of social
      intuitionism in accounting for the moral judgments in a sample of U.S.
      physicians.
AB  - The broad diversity in physicians' judgments on controversial health care topics
      may reflect differences in religious characteristics, political ideologies, and
      moral intuitions. We tested an existing measure of moral intuitions in a new
      population (U.S. physicians) to assess its validity and to determine whether
      physicians' moral intuitions correlate with their views on controversial health
      care topics as well as other known predictors of these intuitions such as
      political affiliation and religiosity. In 2009, we mailed an 8-page questionnaire
      to a random sample of 2000 practicing U.S. physicians from all specialties. The
      survey included the Moral Foundations Questionnaire (MFQ30), along with questions
      on physicians' judgments about controversial health care topics including
      abortion and euthanasia (no moral objection, some moral objection, strong moral
      objection). A total of 1032 of 1895 (54%) physicians responded. Physicians'
      overall mean moral foundations scores were 3.5 for harm, 3.3 for fairness, 2.8
      for loyalty, 3.2 for authority, and 2.7 for sanctity on a 0-5 scale. Increasing
      levels of religious service attendance, having a more conservative political
      ideology, and higher sanctity scores remained the greatest positive predictors of
      respondents objecting to abortion (beta = 0.12, 0.23, 0.14, respectively, each
      p<0.001) as well as euthanasia (beta = 0.08, 0.17, and 0.17, respectively, each
      p<0.001), even after adjusting for demographics. Higher authority scores were
      also significantly negatively associated with objection to abortion (beta = 
      0.12, p<0.01), but not euthanasia. These data suggest that the relative
      importance physicians place on the different categories of moral intuitions may
      predict differences in physicians' judgments about morally controversial topics
      and may interrelate with ideology and religiosity. Further examination of the
      diversity in physicians' moral intuitions may prove illustrative in describing
      and addressing moral differences that arise in medical practice.

PMID- 24023865
TI  - Publication pressure and burn out among Dutch medical professors: a nationwide
      survey.
AB  - BACKGROUND: Publication of scientific research papers is important for
      professionals working in academic medical centres. Quantitative measures of
      scientific output determine status and prestige, and serve to rank universities
      as well as individuals. The pressure to generate maximum scientific output is
      high, and quantitative aspects may tend to dominate over qualitative ones. How
      this pressure influences professionals' perception of science and their personal
      well-being is unknown. METHODS AND FINDINGS: We performed an online survey
      inviting all medical professors (n = 1206) of the 8 academic medical centres in
      The Netherlands to participate. They were asked to fill out 2 questionnaires; a
      validated Publication Pressure Questionnaire and the Maslach Burnout Inventory.
      In total, 437 professors completed the questionnaires. among them, 54% judge that
      publication pressure 'has become excessive', 39% believe that publication
      pressure 'affects the credibility of medical research' and 26% judge that
      publication pressure has a 'sickening effect on medical science'. The burn out
      questionnaire indicates that 24% of medical professors have signs of burn out.
      The number of years of professorship was significantly related with experiencing
      less publication pressure. Significant and strong associations between burn out
      symptoms and the level of perceived publication pressure were found. The main
      limitation is the possibility of response bias. CONCLUSION: A substantial
      proportion of medical professors believe that publication pressure has become
      excessive, and have a cynical view on the validity of medical science. These
      perceptions are statistically correlated to burn out symptoms. Further research
      should address the effects of publication pressure in more detail and identify
      alternative ways to stimulate the quality of medical science.

PMID- 24023866
TI  - NESSTI: norms for environmental sound stimuli.
AB  - In this paper we provide normative data along multiple cognitive and affective
      variable dimensions for a set of 110 sounds, including living and manmade
      stimuli. Environmental sounds are being increasingly utilized as stimuli in the
      cognitive, neuropsychological and neuroimaging fields, yet there is no
      comprehensive set of normative information for these type of stimuli available
      for use across these experimental domains. Experiment 1 collected data from 162
      participants in an on-line questionnaire, which included measures of
      identification and categorization as well as cognitive and affective variables. A
      subsequent experiment collected response times to these sounds. Sounds were
      normalized to the same length (1 second) in order to maximize usage across
      multiple paradigms and experimental fields. These sounds can be freely downloaded
      for use, and all response data have also been made available in order that
      researchers can choose one or many of the cognitive and affective dimensions
      along which they would like to control their stimuli. Our hope is that the
      availability of such information will assist researchers in the fields of
      cognitive and clinical psychology and the neuroimaging community in choosing well
      controlled environmental sound stimuli, and allow comparison across multiple
      studies. 

PMID- 24023867
TI  - Acute stress alters amygdala microRNA miR-135a and miR-124 expression: inferences
      for corticosteroid dependent stress response.
AB  - The amygdala is a brain structure considered a key node for the regulation of
      neuroendocrine stress response. Stress-induced response in amygdala is
      accomplished through neurotransmitter activation and an alteration of gene
      expression. MicroRNAs (miRNAs) are important regulators of gene expression in the
      nervous system and are very well suited effectors of stress response for their
      ability to reversibly silence specific mRNAs. In order to study how acute stress
      affects miRNAs expression in amygdala we analyzed the miRNA profile after two
      hours of mouse restraint, by microarray analysis and reverse transcription real
      time PCR. We found that miR-135a and miR-124 were negatively regulated. Among in
      silico predicted targets we identified the mineralocorticoid receptor (MR) as a
      target of both miR-135a and miR-124. Luciferase experiments and endogenous
      protein expression analysis upon miRNA upregulation and inhibition allowed us to
      demonstrate that mir-135a and mir-124 are able to negatively affect the
      expression of the MR. The increased levels of the amygdala MR protein after two
      hours of restraint, that we analyzed by western blot, negatively correlate with
      miR-135a and miR-124 expression. These findings point to a role of miR-135a and
      miR-124 in acute stress as regulators of the MR, an important effector of early
      stress response. 

PMID- 24023869
TI  - Attitudes toward psychiatry as a prospective career among medical students in
      their pre-clinical year in China- a pilot study.
AB  - OBJECTIVE: To understand the attitudes among medical students in China toward
      different medical specialties and to find the factors that influenced their
      choice of career in psychiatry. METHODS: A questionnaire was developed and
      administered to 287 medical students at the Xiangya Medical College, Central
      South University in Changsha, China. All the students were asked to rate the
      importance of five possible factors in choosing a specialty as a vocation: the
      ability to help patients, interesting and challenging work, lifestyle factors,
      financial reward, and prestige. RESULTS: Students reported negative perceptions
      of psychiatry in regard to all five possible factors that were important in
      choosing a specialty as a vocation, especially in financial reward and prestige.
      CONCLUSIONS: Medical students in China have negative attitudes toward psychiatry
      as a career. Some negative beliefs about psychiatry seem to be due to erroneous
      or insufficient knowledge that could be corrected during the course of medical
      education. Some negative attitudes were unlikely to be completely changed until
      the mental health system in China improves.

PMID- 24023868
TI  - European corn borer (Ostrinia nubilalis) induced responses enhance susceptibility
      in maize.
AB  - Herbivore-induced plant responses have been widely described following attack on
      leaves; however, less attention has been paid to analogous local processes that
      occur in stems. Early studies of maize (Zea mays) responses to stem boring by
      European corn borer (ECB, Ostrinianubilalis) larvae revealed the presence of
      inducible acidic diterpenoid phytoalexins, termed kauralexins, and increases in
      the benzoxazinoid 2-hydroxy-4,7-dimethoxy-1,4-benzoxazin-3-one-glucose (HDMBOA
      Glc) after 24 h of herbivory. Despite these rapidly activated defenses, larval
      growth was not altered in short-term feeding assays. Unexpectedly, ECB growth
      significantly improved in assays using stem tissue preconditioned by 48 h of
      larval tunneling. Correspondingly, measures of total soluble protein increased
      over 2.6-fold in these challenged tissues and were accompanied by elevated levels
      of sucrose and free linoleic acid. While microarray analyses revealed up
      regulation of over 1100 transcripts, fewer individual protein increases were
      demonstrable. Consistent with induced endoreduplication, both wounding and ECB
      stem attack resulted in similar significant expansion of the nucleus, nucleolus
      and levels of extractable DNA from challenged tissues. While many of these
      responses are triggered by wounding alone, biochemical changes further enhanced
      in response to ECB may be due to larval secreted effectors. Unlike other
      Lepidoptera examined, ECB excrete exceedingly high levels of the auxin indole-3
      acetic acid (IAA) in their frass which is likely to contact and contaminate the
      surrounding feeding tunnel. Stem exposure to a metabolically stable auxin, such
      as 2,4-dichlorophenoxyacetic acid (2,4-D), promoted significant protein
      accumulation above wounding alone. As a future testable hypothesis, we propose
      that ECB-associated IAA may function as a candidate herbivore effector promoting
      the increased nutritional content of maize stems. 

PMID- 24023870
TI  - The anti-Pseudomonas aeruginosa antibody Panobacumab is efficacious on acute
      pneumonia in neutropenic mice and has additive effects with meropenem.
AB  - Pseudomonas aeruginosa (P. aeruginosa) infections are associated with
      considerable morbidity and mortality in immunocompromised patients due to
      antibiotic resistance. Therefore, we investigated the efficacy of the anti-P.
      aeruginosa serotype O11 lipopolysaccharide monoclonal antibody Panobacumab in a
      clinically relevant murine model of neutropenia induced by cyclophosphamide and
      in combination with meropenem in susceptible and meropenem resistant P.
      aeruginosa induced pneumonia. We observed that P. aeruginosa induced pneumonia
      was dramatically increased in neutropenic mice compared to immunocompetent mice.
      First, Panobacumab significantly reduced lung inflammation and enhanced bacterial
      clearance from the lung of neutropenic host. Secondly, combination of Panobacumab
      and meropenem had an additive effect. Third, Panobacumab retained activity on a
      meropenem resistant P. aeruginosa strain. In conclusion, the present data
      established that Panobacumab contributes to the clearance of P. aeruginosa in
      neutropenic hosts as well as in combination with antibiotics in immunocompetent
      hosts. This suggests beneficial effects of co-treatment even in immunocompromised
      individuals, suffering most of the morbidity and mortality of P. aeruginosa
      infections. 

PMID- 24023871
TI  - The HDAC inhibitor LBH589 induces ERK-dependent prometaphase arrest in prostate
      cancer via HDAC6 inactivation and down-regulation.
AB  - Histone deacetylase inhibitors (HDACIs) have potent anti-cancer activity in a
      variety of cancer models. Understanding the molecular mechanisms involved in the
      therapeutic responsiveness of HDACI is needed before its clinical application.
      This study aimed to determine if a potent HDACI, LBH589 (Panobinostat), had
      differential therapeutic responsiveness towards LNCaP and PC-3 prostate cancer
      (PCa) cells. The former showed prometaphase arrest with subsequent apoptosis upon
      LBH589 treatment, while the latter was less sensitive and had late G2 arrest. The
      LBH589 treatment down-regulated HDAC6 and sustained ERK activation, and
      contributed to prometaphase arrest. Mechanistically, LBH589 inhibited HDAC6
      activity, caused its dissociation from protein phosphatase PP1alpha, and
      increased 14-3-3zeta acetylation. Acetylated 14-3-3zeta released its mask effect
      on serine 259 of c-Raf and serine 216 of Cdc25C subsequent to de-phosphorylation
      by PP1alpha, which contributed to ERK activation. Enhanced ERK activity by LBH589
      further down-regulated HDAC6 protein levels and sustained ERK activation by free
      forward regulation. The sustained Cdc25C and ERK activation resulted in early M
      phase (prometaphase) arrest and subsequent apoptosis in the most sensitive LNCaP
      cells but not in PC-3 cells. This study provides pre-clinical evidence that HDAC6
      may serve as a sensitive therapeutic target in the treatment of prostate cancer
      with HDACI LBH589 for clinical translation. This study also posits a novel
      mechanism of HDAC6 participation in regulating the c-Raf-PP1-ERK signaling
      pathway and contributing to M phase cell-cycle transition. 

PMID- 24023873
TI  - Disturbed resting functional inter-hemispherical connectivity of the ventral
      attentional network in alpha band is associated with unilateral spatial neglect.
AB  - Unilateral spatial neglect (USN) is one of the most common symptoms of right
      hemisphere damage; its classical symptom is that patients fail to respond to
      information on their left side. It has been postulated that disturbance of 2
      separate attentional networks relates to the occurrence of USN. However, little
      is known about the underlying mechanism and neuronal substrates. In this study,
      we measured spontaneous neural activity by means of magnetoencephalography in 13
      patients with brain damage and 5 control subjects. To study the relationship
      between functional connectivity at rest and severity of USN symptoms, we
      determined the imaginary coherence values relating to the inter-hemispherical
      ventral and dorsal attentional networks, as well as the clinical severity of USN
      using neuropsychological tests and behavioral rating scales. The present results
      showed that inter-hemispherical connectivity in the ventral attentional network,
      especially between the left and right angular gyri, detected in the alpha band is
      associated with the severity of USN symptoms. This may suggest that connectivity
      of inter-hemispherical homologous regions of the ventral attentional network in
      the alpha band could be one of the biomarkers of attentional network imbalance
      occurring in patients with USN. 

PMID- 24023872
TI  - Twist1 controls lung vascular permeability and endotoxin-induced pulmonary edema
      by altering Tie2 expression.
AB  - Tight regulation of vascular permeability is necessary for normal development and
      deregulated vascular barrier function contributes to the pathogenesis of various
      diseases, including acute respiratory distress syndrome, cancer and inflammation.
      The angiopoietin (Ang)-Tie2 pathway is known to control vascular permeability.
      However, the mechanism by which the expression of Tie2 is regulated to control
      vascular permeability has not been fully elucidated. Here we show that
      transcription factor Twist1 modulates pulmonary vascular leakage by altering the
      expression of Tie2 in a context-dependent way. Twist1 knockdown in cultured human
      lung microvascular endothelial cells decreases Tie2 expression and
      phosphorylation and increases RhoA activity, which disrupts cell-cell junctional
      integrity and increases vascular permeability in vitro. In physiological
      conditions, where Ang1 is dominant, pulmonary vascular permeability is elevated
      in the Tie2-specific Twist1 knockout mice. However, depletion of Twist1 and
      resultant suppression of Tie2 expression prevent increase in vascular
      permeability in an endotoxin-induced lung injury model, where the balance of Angs
      shifts toward Ang2. These results suggest that Twist1-Tie2-Angs signaling is
      important for controlling vascular permeability and modulation of this mechanism
      may lead to the development of new therapeutic approaches for pulmonary edema and
      other diseases caused by abnormal vascular permeability. 

PMID- 24023875
TI  - Overexpression of E2F1 promotes tumor malignancy and correlates with TNM stages
      in clear cell renal cell carcinoma.
AB  - BACKGROUND: Transcription factor E2F1 exerts effects on many types of cancers. As
      an upstream regulator of a host of genes, E2F1 can trigger diverse aberrant
      transcription processes that may dominate malignancy. Clear cell renal cell
      carcinoma (ccRCC) is the most common subtype in renal cell carcinoma which
      displays high malignancy and has a shortage of biomarkers in clinics. Our study
      aimed to explore the function of E2F1 in ccRCC and its correlation with
      clinicopathological parameters. METHODOLOGY/PRINCIPLE FINDINGS: Transcription
      factor E2F1 was mainly distributed in cancer cell nucleus and mRNA expression
      significantly increased in 72 cases of clear cell renal cell carcinoma (ccRCC)
      tissues compared with adjacent non-cancerous kidney tissues (p<0.001). The
      protein expression was consistent with mRNA expression. Further analysis in 92
      cases indicated that E2F1 mRNA level expression was associated with the tumor
      pathologic parameters embracing diameter, Fuhrman tumor grade, pT stage, TNM
      stage grouping and macrovascular infiltration (MAVI). These surgical specimens
      had high grade tumors accompanied with an elevated E2F1 expression. Moreover,
      E2F1 transfection was found to contribute significantly to cancer cell
      proliferation, migration and invasion in vitro. CONCLUSIONS/SIGNIFICANCE:
      Overexpression of E2F1 may be a key event in the local and vascular infiltration
      of ccRCC indicated by the activation of matrix metalloproteinase (MMP) 2 and
      MMP9. These findings highlighted the implication of E2F1's function in the
      metastatic process. Furthermore, the clinical relevance of E2F1 in ccRCC pointed
      to a potential new therapeutic target.

PMID- 24023874
TI  - Functional cross talk between CXCR4 and PDGFR on glioblastoma cells is essential
      for migration.
AB  - Glioblastoma (GBM) is the most common and aggressive form of brain tumor,
      characterized by high migratory behavior and infiltration in brain parenchyma
      which render classic therapeutic approach ineffective. The migratory behaviour of
      GBM cells could be conditioned by a number of tissue- and glioma-derived
      cytokines and growth factors. Although the pro-migratory action of CXCL12 on GBM
      cells in vitro and in vivo is recognized, the molecular mechanisms involved are
      not clearly identified. In fact the signaling pathways involved in the pro
      migratory action of CXCL12 may differ in individual glioblastoma and integrate
      with those resulting from abnormal expression and activation of growth factor
      receptors. In this study we investigated whether some of the receptor tyrosine
      kinases commonly expressed in GBM cells could cooperate with CXCL12/CXCR4 in
      their migratory behavior. Our results show a functional cross-talk between CXCR4
      and PDGFR which appears to be essential for GBM chemotaxis. 

PMID- 24023876
TI  - White blood cell count measured prior to cancer development is associated with
      future risk of venous thromboembolism--the Tromso study.
AB  - BACKGROUND: Elevated white blood cell (WBC) count is associated with risk of
      venous thromboembolism (VTE) in cancer patients initiating chemotherapy. It is
      not known whether the risk of VTE by WBC count in cancer patients is causal or
      merely a consequence of the malignant disease. To address this question, we
      studied the association between WBC count, measured prior to cancer development,
      and risk of VTE in subjects who did and did not develop cancer during follow-up
      in a prospective population-based study. METHODS: Baseline characteristics,
      including WBC and neutrophil counts, were measured in 24304 initially cancer-free
      subjects who participated in the Tromso Study in 1994-1995. Incident cancer
      diagnosis and VTE events were registered up to September 1, 2007. In the cancer
      cohort, WBC and neutrophil counts were measured in average 7.1 years before
      cancer development. Cox-regression models were used to calculate hazard ratios
      (HRs) for VTE by WBC and neutrophil counts as categorized variables (<40(th), 40
      80(th), and >80(th) percentile) with 95% confidence intervals (CIs). RESULTS:
      During follow-up, 1720 subjects developed cancer and there were 388 VTE events,
      of which 116 occurred in the cancer-group (6.9 per 1000 person-years) and 272 in
      the cancer-free group (1.1 per 1000 person-years). In those who developed cancer,
      WBC count above the 80(th) percentile (>= 8.6 x 10(9) cells/L) was associated
      with a 2.4-fold higher risk (HR 2.36, 95% CI: 1.44-3.87) of VTE compared to WBC
      count below the 40(th) percentile (<6.4 x 10(9) cells/L). No association was
      found between WBC count and VTE in those who stayed cancer-free (HR 0.94, 95% CI
      0.65-1.36). Similar findings were observed for neutrophils. COMMENT: Pre-cancer
      WBC count was associated with risk of VTE in cancer patients, but not in cancer
      free subjects. Our findings suggest that leukocytes may play a causal role in
      cancer-related VTE rather than only reflecting the low-grade inflammation
      associated with cancer.

PMID- 24023877
TI  - Diversity among clients of female sex workers in India: comparing risk profiles
      and intervention impact by site of solicitation. implications for the
      vulnerability of less visible female sex workers.
AB  - BACKGROUND: It seems generally accepted that targeted interventions in India have
      been successful in raising condom use between female sex workers (FSWs) and their
      clients. Data from clients of FSWs have been under-utilised to analyse the risk
      environments and vulnerability of both partners. METHODS: The 2009 Integrated
      Biological and Behavioural Assessment survey sampled clients of FSWs at hotspots
      in Andhra Pradesh, Maharashtra and Tamil Nadu (n=5040). The risk profile of
      clients in terms of sexual networking and condom use are compared across usual
      pick-up place. We used propensity score matching (PSM) to estimate the average
      treatment effect on treated (ATT) of intervention messages on clients' consistent
      condom use with FSW. RESULTS: Clients of the more hidden sex workers who solicit
      from home or via phone or agents had more extensive sexual networks, reporting
      casual female partners as well as anal intercourse with male partners and FSW.
      Clients of brothel-based sex workers, who were the least educated, reported the
      fewest number/categories of partners, least anal sex, and lowest condom use
      (41%). Consistent condom use varied widely by state: 65% in Andhra Pradesh, 36%
      in Maharashtra and 29% in Tamil Nadu. Exposure to intervention messages on
      sexually transmitted infections was lowest among men frequenting brothels (58%),
      and highest among men soliciting less visible sex workers (70%). Exposure had
      significant impact on consistent condom use, including among clients of home
      based sex workers (ATT 21%; p=0.001) and among men soliciting other more hidden
      FSW (ATT 17%; p=0.001). In Tamil Nadu no impact could be demonstrated.
      CONCLUSION: Commercial sex happens between two partners and both need to be, and
      can be, reached by intervention messages. Commercial sex is still largely
      unprotected and as the sex industry gets more diffuse a greater focus on reaching
      clients of sex workers seems important given their extensive sexual networks.

PMID- 24023879
TI  - Pseudophosphorylated alphaB-crystallin is a nuclear chaperone imported into the
      nucleus with help of the SMN complex.
AB  - The human small heat shock protein alphaB-crystallin (HspB5) is a molecular
      chaperone which is mainly localized in the cytoplasm. A small fraction can also
      be found in nuclear speckles, of which the localization is mediated by
      successional phosphorylation at Ser-59 and Ser-45. alphaB-crystallin does not
      contain a canonical nuclear localization signal sequence and the mechanism by
      which alphaB-crystallin is imported into the nucleus is not known. Here we show
      that after heat shock pseudophosphorylated alphaB-crystallin mutant alphaB-STD,
      in which all three phosphorylatable serine residues (Ser-19, Ser-45 and Ser-59)
      were replaced by negatively charged aspartate residues, is released from the
      nuclear speckles. This allows alphaB-crystallin to chaperone proteins in the
      nucleoplasm, as shown by the ability of alphaB-STD to restore nuclear firefly
      luciferase activity after a heat shock. With the help of a yeast two-hybrid
      screen we found that alphaB-crystallin can interact with the C-terminal part of
      Gemin3 and confirmed this interaction by co-immunoprecipitation. Gemin3 is a
      component of the SMN complex, which is involved in the assembly and nuclear
      import of U-snRNPs. Knockdown of Gemin3 in an in situ nuclear import assay
      strongly reduced the accumulation of alphaB-STD in nuclear speckles. Furthermore,
      depletion of SMN inhibited nuclear import of fluorescently labeled recombinant
      alphaB-STD in an in vitro nuclear import assay, which could be restored by the
      addition of purified SMN complex. These results show that the SMN-complex
      facilitates the accumulation of hyperphosphorylated alphaB-crystallin in nuclear
      speckles, thereby creating a chaperone depot enabling a rapid chaperone function
      in the nucleus in response to stress. 

PMID- 24023878
TI  - Aquaporin-4 inhibition mediates piroxicam-induced neuroprotection against focal
      cerebral ischemia/reperfusion injury in rodents.
AB  - BACKGROUND AND PURPOSE: Aquaporin-4(AQP4) is an abundant water channel protein in
      brain that regulates water transport to maintain homeostasis. Cerebral edema
      resulting from AQP4 over expression is considered to be one of the major
      determinants for progressive neuronal insult during cerebral ischemia. Although,
      both upregulation and downregulation of AQP4 expression is associated with brain
      pathology, over expression of AQP4 is one of the chief contributors of water
      imbalance in brain during ischemic pathology. We have found that Piroxicam binds
      to AQP4 with optimal binding energy value. Thus, we hypothesized that Piroxicam
      is neuroprotective in the rodent cerebral ischemic model by mitigating cerebral
      edema via AQP4 regulation. METHODS: Rats were treated with Piroxicam OR placebo
      at 30 min prior, 2 h post and 4 h post 60 minutes of MCAO followed by 24 hour
      reperfusion. Rats were evaluated for neurological deficits and motor function
      just before sacrifice. Brains were harvested for infarct size estimation, water
      content measurement, biochemical analysis, RT-PCR and western blot experiments.
      RESULTS: Piroxicam pretreatment thirty minutes prior to ischemia and four hour
      post reperfusion afforded neuroprotection as evident through significant
      reduction in cerebral infarct volume, improvement in motor behavior, neurological
      deficit and reduction in brain edema. Furthermore, ischemia induced surge in
      levels of nitrite and malondialdehyde were also found to be significantly reduced
      in ischemic brain regions in treated animals. This neuroprotection was found to
      be associated with inhibition of acid mediated rise in intracellular calcium
      levels and also downregulated AQP4 expression. CONCLUSIONS: Findings of the
      present study provide significant evidence that Piroxicam acts as a potent AQP4
      regulator and renders neuroprotection in focal cerebral ischemia. Piroxicam could
      be clinically exploited for the treatment of brain stroke along with other anti
      stroke therapeutics in future.

PMID- 24023880
TI  - Design and implementation of a custom built optical projection tomography system.
AB  - Optical projection tomography (OPT) is an imaging modality that has, in the last
      decade, answered numerous biological questions owing to its ability to view gene
      expression in 3 dimensions (3D) at high resolution for samples up to several
      cm(3). This has increased demand for a cabinet OPT system, especially for mouse
      embryo phenotyping, for which OPT was primarily designed for. The Medical
      Research Council (MRC) Technology group (UK) released a commercial OPT system,
      constructed by Skyscan, called the Bioptonics OPT 3001 scanner that was installed
      in a limited number of locations. The Bioptonics system has been discontinued and
      currently there is no commercial OPT system available. Therefore, a few research
      institutions have built their own OPT system, choosing parts and a design
      specific to their biological applications. Some of these custom built OPT systems
      are preferred over the commercial Bioptonics system, as they provide improved
      performance based on stable translation and rotation stages and up to date CCD
      cameras coupled with objective lenses of high numerical aperture, increasing the
      resolution of the images. Here, we present a detailed description of a custom
      built OPT system that is robust and easy to build and install. Included is a
      hardware parts list, instructions for assembly, a description of the acquisition
      software and a free download site, and methods for calibration. The described OPT
      system can acquire a full 3D data set in 10 minutes at 6.7 micron isotropic
      resolution. The presented guide will hopefully increase adoption of OPT
      throughout the research community, for the OPT system described can be
      implemented by personnel with minimal expertise in optics or engineering who have
      access to a machine shop. 

PMID- 24023881
TI  - Regulation of sialidase production in Clostridium perfringens by the orphan
      sensor histidine kinase ReeS.
AB  - Clostridium perfringens is ubiquitous in nature and is often found as a commensal
      of the human and animal gastrointestinal tract. It is the primary etiological
      agent of clostridial myonecrosis, or gas gangrene, a serious infection that
      results in extensive tissue necrosis due to the action of one or more potent
      extracellular toxins. alpha-toxin and perfringolysin O are the major
      extracellular toxins involved in the pathogenesis of gas gangrene, but histotoxic
      strains of C. perfringens, such as strain 13, also produce many degradative
      enzymes such as collagenases, hyaluronidases, sialidases and the cysteine
      protease, alpha-clostripain. The production of many of these toxins is regulated
      either directly or indirectly by the global VirSR two-component signal
      transduction system. By isolating a chromosomal mutant and carrying out
      microarray analysis we have identified an orphan sensor histidine kinase, which
      we have named ReeS (regulator of extracellular enzymes sensor). Expression of the
      sialidase genes nanI and nanJ was down-regulated in a reeS mutant. Since
      complementation with the wild-type reeS gene restored nanI and nanJ expression to
      wild-type levels, as shown by quantitative reverse transcription-PCR and
      sialidase assays we concluded that ReeS positively regulates the expression of
      these sialidase genes. However, mutation of the reeS gene had no significant
      effect on virulence in the mouse myonecrosis model. Sialidase production in C.
      perfringens has been previously shown to be regulated by both the VirSR system
      and RevR. In this report, we have analyzed a previously unknown sensor histidine
      kinase, ReeS, and have shown that it also is involved in controlling the
      expression of sialidase genes, adding further complexity to the regulatory
      network that controls sialidase production in C. perfringens. 

PMID- 24023882
TI  - Blocking Plasmodium falciparum development via dual inhibition of hemoglobin
      degradation and the ubiquitin proteasome system by MG132.
AB  - Among key potential drug target proteolytic systems in the malaria parasite
      Plasmodium falciparum are falcipains, a family of hemoglobin-degrading cysteine
      proteases, and the ubiquitin proteasomal system (UPS), which has fundamental
      importance in cellular protein turnover. Inhibition of falcipains blocks parasite
      development, primarily due to inhibition of hemoglobin degradation that serves as
      a source of amino acids for parasite growth. Falcipains prefer P2 leucine in
      substrates and peptides, and their peptidyl inhibitors with leucine at the P2
      position show potent antimalarial activity. The peptidyl inhibitor MG132 (Z-Leu
      Leu-Leu-CHO) is a widely used proteasome inhibitor, which also has P2 leucine,
      and has also been shown to inhibit parasite development. However, the
      antimalarial targets of MG132 are unclear. We investigated whether MG132 blocks
      malaria parasite development by inhibiting hemoglobin degradation and/or by
      targeting the UPS. P. falciparum was cultured with inhibitors of the UPS (MG132,
      epoxomicin, and lactacystin) or falcipains (E64), and parasites were assessed for
      morphologies, extent of hemoglobin degradation, and accumulation of ubiquitinated
      proteins. MG132, like E64 and unlike epoxomicin or lactacystin, blocked parasite
      development, with enlargement of the food vacuole and accumulation of undegraded
      hemoglobin, indicating inhibition of hemoglobin degradation by MG132, most likely
      due to inhibition of hemoglobin-degrading falcipain cysteine proteases. Parasites
      cultured with epoxomicin or MG132 accumulated ubiquitinated proteins to a
      significantly greater extent than untreated or E64-treated parasites, indicating
      that MG132 inhibits the parasite UPS as well. Consistent with these findings,
      MG132 inhibited both cysteine protease and UPS activities present in soluble
      parasite extracts, and it strongly inhibited recombinant falcipains. MG132 was
      highly selective for inhibition of P. falciparum (IC50 0.0476 uM) compared to
      human peripheral blood mononuclear cells (IC50 10.8 uM). Thus, MG132 inhibits two
      distinct proteolytic systems in P. falciparum, and it may serve as a lead
      molecule for development of dual-target inhibitors of malaria parasites. 

PMID- 24023883
TI  - Evolutionary origin of the Scombridae (tunas and mackerels): members of a
      paleogene adaptive radiation with 14 other pelagic fish families.
AB  - Uncertainties surrounding the evolutionary origin of the epipelagic fish family
      Scombridae (tunas and mackerels) are symptomatic of the difficulties in resolving
      suprafamilial relationships within Percomorpha, a hyperdiverse teleost radiation
      that contains approximately 17,000 species placed in 13 ill-defined orders and
      269 families. Here we find that scombrids share a common ancestry with 14
      families based on (i) bioinformatic analyses using partial mitochondrial and
      nuclear gene sequences from all percomorphs deposited in GenBank (10,733
      sequences) and (ii) subsequent mitogenomic analysis based on 57 species from
      those targeted 15 families and 67 outgroup taxa. Morphological heterogeneity
      among these 15 families is so extraordinary that they have been placed in six
      different perciform suborders. However, members of the 15 families are either
      coastal or oceanic pelagic in their ecology with diverse modes of life,
      suggesting that they represent a previously undetected adaptive radiation in the
      pelagic realm. Time-calibrated phylogenies imply that scombrids originated from a
      deep-ocean ancestor and began to radiate after the end-Cretaceous when large
      predatory epipelagic fishes were selective victims of the Cretaceous-Paleogene
      mass extinction. We name this clade of open-ocean fishes containing Scombridae
      "Pelagia" in reference to the common habitat preference that links the 15
      families. 

PMID- 24023885
TI  - Cipactlichthys scutatus, gen. nov., sp. nov. a new Halecomorph (Neopterygii,
      Holostei) from the Lower Cretaceous Tlayua Formation of Mexico.
AB  - Based on specimens from the Lower Cretaceous Tlayua Formation of Mexico, we
      describe a new genus and species of Halecomorphi, Cipactlichthysscutatus gen. et
      sp. nov, which exhibits several diagnostic characters such as the dermal bones
      and the scales with ganoin and highly ornamented by numerous tubercles and
      ridges; parietal slightly longer than wide with approximately the same length as
      the frontal; jaws extending far, below the posterior orbital margin, reaching the
      posterior third of the postorbital plate; maxilla with a convexly rounded
      posterior margin; pectoral fin margins slightly convex; first ray of pectoral fin
      very long, reaching the posterior edge of the pelvic fin; about 37 preural
      vertebrae and 7 Ural centra; a series of hypertrophied scales just posterior to
      the cleithrum; arrangement of flank scales with two rows of deep scales; a series
      of dorsal and ventral scutes forming the dorsal and ventral midline, between the
      dorsal and anal fins and the caudal fin. A phylogenetic analysis including two
      outgroups and eleven neopterygians confirmed the monophyly of the Holostei as
      well as the monophyly of the Halecomorphi, although this last clade is weakly
      supported. Cipactlichthysscutatus was hypothesised as the sister-group of the
      (Ionoscopiformes + Amiiformes). 

PMID- 24023884
TI  - GFI1 is repressed by p53 and inhibits DNA damage-induced apoptosis.
AB  - GFI1 is a transcriptional repressor that plays a critical role in hematopoiesis
      and has also been implicated in lymphomagenesis. It is still poorly understood
      how GFI1 expression is regulated in the hematopoietic system. We show here that
      GFI1 transcription was repressed by the tumor suppressor p53 in hematopoietic
      cells. Knockdown of p53 resulted in increased GFI1 expression and abolished DNA
      damage-induced GFI1 downregulation. In contrast, GFI1 expression was reduced and
      its downregulation in response to DNA damage was rescued upon restoration of p53
      function in p53-deficient cells. In luciferase reporter assays, wild type p53,
      but not a DNA binding-defective p53 mutant, repressed the GFI1 promoter.
      Chromatin immunoprecipitation (ChIP) assays demonstrated that p53 bound to the
      proximal region of the GFI1 promoter. Detailed mapping of the GFI1 promoter
      indicated that GFI1 core promoter region spanning from -33 to +6 bp is sufficient
      for p53-mediated repression. This core promoter region contains a putative p53
      repressive response element, mutation of which abolished p53 binding to and
      repression of GFI1 promoter. Significantly, apoptosis induced by DNA damage was
      inhibited upon Gfi1 overexpression, but augmented following GFI1 knockdown. Our
      data establish for the first time that GFI1 is repressed by p53 and add to our
      understanding of the roles of GFI1 in normal hematopoiesis and lymphomagenesis. 

PMID- 24023886
TI  - Evolutionary history of chordate PAX genes: dynamics of change in a complex gene
      family.
AB  - Paired box (PAX) genes are transcription factors that play important roles in
      embryonic development. Although the PAX gene family occurs in animals only, it is
      widely distributed. Among the vertebrates, its 9 genes appear to be the product
      of complete duplication of an original set of 4 genes, followed by an additional
      partial duplication. Although some studies of PAX genes have been conducted, no
      comprehensive survey of these genes across the entire taxonomic unit has yet been
      attempted. In this study, we conducted a detailed comparison of PAX sequences
      from 188 chordates, which revealed restricted variation. The absence of PAX4 and
      PAX8 among some species of reptiles and birds was notable; however, all 9 genes
      were present in all 74 mammalian genomes investigated. A search for signatures of
      selection indicated that all genes are subject to purifying selection, with a
      possible constraint relaxation in PAX4, PAX7, and PAX8. This result indicates
      asymmetric evolution of PAX family genes, which can be associated with the
      emergence of adaptive novelties in the chordate evolutionary trajectory. 

PMID- 24023887
TI  - Identification and characterization of the regions involved in the nuclear
      translocation of the heterodimeric leishmanial DNA topoisomerase IB.
AB  - Leishmania donovani, the causative organism for visceral leishmaniasis, contains
      a unique heterodimeric DNA-topoisomerase IB (LdTopIB). LdTopIB is a heterodimer
      made up of a large subunit and a small subunit that must interact with each other
      to build an active enzyme able to solve the topological tensions on the DNA. As
      LdTopIB is located within the nucleus, one or more nuclear localization signals
      (NLS) should exist to ensure its nuclear translocation. In this report three
      novel NLS have been identified through a sequential deletion study of the genes
      encoding of both subunits fused to that encoding the green fluorescent protein
      (GFP). NLS1 is a highly basic sequence of 43 amino acids in the C-terminal
      extension of the large protomer. We found two well-defined sequences in the small
      protomer: NLS2 is a 10-amino acid motif located in the N-terminal extension of
      the protein; NLS3 consists of a complex region of 28 amino acids placed in the
      vicinity of the catalytic Tyr-222 included at the conserved SKINY signature
      within the C-terminal. Furthermore, by means of yeast cell viability assays,
      conducted with several LdTopIB chimeras lacking any of the NLS motives, we have
      revealed that both subunits are transported independently to the nucleus. There
      was no evidence of LdTopIB accumulation in mitochondria or association to the
      kinetoplast DNA network. The results rule out the former hypothesis, which
      attributes nucleocytoplasmic transport of LdTopIB entirely to the large subunit.
      The LdTopIB is localized to the nucleus only. 

PMID- 24023888
TI  - miR-206 represses hypertrophy of myogenic cells but not muscle fibers via
      inhibition of HDAC4.
AB  - microRNAs regulate the development of myogenic progenitors, and the formation of
      skeletal muscle fibers. However, the role miRNAs play in controlling the growth
      and adaptation of post-mitotic musculature is less clear. Here, we show that
      inhibition of the established pro-myogenic regulator miR-206 can promote
      hypertrophy and increased protein synthesis in post-mitotic cells of the myogenic
      lineage. We have previously demonstrated that histone deacetylase 4 (HDAC4) is a
      target of miR-206 in the regulation of myogenic differentiation. We confirmed
      that inhibition of miR-206 de-repressed HDAC4 accumulation in cultured myotubes.
      Importantly, inhibition of HDAC4 activity by valproic acid or sodium butyrate
      prevented hypertrophy of myogenic cells otherwise induced by inhibition of miR
      206. To test the significance of miRNA-206 as a regulator of skeletal muscle mass
      in vivo, we designed recombinant adeno-associated viral vectors (rAAV6 vectors)
      expressing miR-206, or a miR-206 "sponge," featuring repeats of a validated miR
      206 target sequence. We observed that over-expression or inhibition of miR-206 in
      the muscles of mice decreased or increased endogenous HDAC4 levels respectively,
      but did not alter muscle mass or myofiber size. We subsequently manipulated miR
      206 levels in muscles undergoing follistatin-induced hypertrophy or denervation
      induced atrophy (models of muscle adaptation where endogenous miR-206 expression
      is altered). Vector-mediated manipulation of miR-206 activity in these models of
      cell growth and wasting did not alter gain or loss of muscle mass respectively.
      Our data demonstrate that although the miR-206/HDAC4 axis operates in skeletal
      muscle, the post-natal expression of miR-206 is not a key regulator of basal
      skeletal muscle mass or specific modes of muscle growth and wasting. These
      studies support a context-dependent role of miR-206 in regulating hypertrophy
      that may be dispensable for maintaining or modifying the adult skeletal muscle
      phenotype--an important consideration in relation to the development of
      therapeutics designed to manipulate microRNA activity in musculature.

PMID- 24023889
TI  - Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog
      and human skin.
AB  - There remains a critical need for new therapeutics that promote wound healing in
      patients suffering from chronic skin wounds. This is, in part, due to a shortage
      of simple, physiologically and clinically relevant test systems for investigating
      candidate agents. The skin of amphibians possesses a remarkable regenerative
      capacity, which remains insufficiently explored for clinical purposes. Combining
      comparative biology with a translational medicine approach, we report the
      development and application of a simple ex vivo frog (Xenopus tropicalis) skin
      organ culture system that permits exploration of the effects of amphibian skin
      derived agents on re-epithelialisation in both frog and human skin. Using this
      amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel
      stimulant of epidermal regeneration. Moving to a complementary human ex vivo
      wounded skin assay, we demonstrate that the effects of TRH are conserved across
      the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo
      epidermis in organ-cultured human skin, accompanied by increased keratinocyte
      proliferation and wound healing-associated differentiation (cytokeratin 6
      expression). Thus, TRH represents a novel, clinically relevant neuroendocrine
      wound repair promoter that deserves further exploration. These complementary frog
      and human skin ex vivo assays encourage a comparative biology approach in future
      wound healing research so as to facilitate the rapid identification and
      preclinical testing of novel, evolutionarily conserved, and clinically relevant
      wound healing promoters. 

PMID- 24023890
TI  - Characterisation of the transcriptomes of genetically diverse Listeria
      monocytogenes exposed to hyperosmotic and low temperature conditions reveal
      global stress-adaptation mechanisms.
AB  - The ability of Listeria monocytogenes to adapt to various food and food-
      processing environments has been attributed to its robustness, persistence and
      prevalence in the food supply chain. To improve the present understanding of
      molecular mechanisms involved in hyperosmotic and low-temperature stress
      adaptation of L. monocytogenes, we undertook transcriptomics analysis on three
      strains adapted to sub-lethal levels of these stress stimuli and assessed
      functional gene response. Adaptation to hyperosmotic and cold-temperature stress
      has revealed many parallels in terms of gene expression profiles in strains
      possessing different levels of stress tolerance. Gene sets associated with
      ribosomes and translation, transcription, cell division as well as fatty acid
      biosynthesis and peptide transport showed activation in cells adapted to either
      cold or hyperosmotic stress. Repression of genes associated with carbohydrate
      metabolism and transport as well as flagella was evident in stressed cells,
      likely linked to activation of CodY regulon and consequential cellular energy
      conservation. 

PMID- 24023891
TI  - Intraoperative evaluation of transmitral pressure gradients after edge-to-edge
      mitral valve repair.
AB  - OBJECTIVE: Edge-to-edge repair of the mitral valve (MV) has been described as a
      viable option used for the surgical management of mitral regurgitation (MR).
      Based on the significant changes in MV geometry associated with this technique,
      we hypothesized that edge-to-edge MV repairs are associated with higher
      intraoperative transmitral pressure gradients (TMPG) compared to conventional
      methods. METHODS: Patient records and intraoperative transesophageal
      echocardiography (TEE) examinations of 552 consecutive patients undergoing MV
      repair at a single institution over a three year period were assessed. After
      separation from cardiopulmonary bypass (CPB), peak and mean TMPG were recorded
      for each patient and subsequently analyzed. RESULTS: 84 patients (15%) underwent
      edge-to-edge MV repair. Peak and mean TMPG were significantly higher compared to
      gradients in patients undergoing conventional repairs: 10.7 +/- 0.5 mmHg vs 7.1
      +/- 0.2 mmHg; P<0.0001 and 4.3 +/- 0.2 mmHg vs 2.8 +/- 0.1 mmHg; P<0.0001. Only
      patients with mean TMPG >= 7 mmHg (n = 9) required prompt reoperation for
      iatrogenic mitral stenosis (MS). No differences in peak and mean TMPG were
      observed among edge-to-edge repairs performed in isolation, compared to those
      performed in combination with annuloplasty: 11.0 +/- 0.7 mmHg vs 10.3 +/- 0.6
      mmHg and 4.4 +/- 0.3 mmHg vs 4.3 +/- 0.3 mmHg. There were no differences in TMPG
      between various types of annuloplasty techniques used in combination with the
      edge-to-edge repairs. CONCLUSIONS: Edge-to-edge MV repairs are associated with
      higher intraoperative peak and mean TMPG after separation from CPB compared to
      conventional repair techniques. Unless gradients are severely elevated, these
      findings are not necessarily suggestive of iatrogenic MS. Thus, in the immediate
      postoperative period mildly elevated TMPG can be expected and tolerated after
      edge-to-edge mitral repairs.

PMID- 24023892
TI  - Adaptation of bird communities to farmland abandonment in a mountain landscape.
AB  - Widespread farmland abandonment has led to significant landscape transformations
      of many European mountain areas. These semi-natural multi-habitat landscapes are
      important reservoirs of biodiversity and their abandonment has important
      conservation implications. In multi-habitat landscapes the adaptation of
      communities depends on the differential affinity of the species to the available
      habitats. We use nested species-area relationships (SAR) to model species
      richness patterns of bird communities across scales in a mountain landscape, in
      NW Portugal. We compare the performance of the classic-SAR and the countryside
      SAR (i.e. multi-habitat) models at the landscape scale, and compare species
      similarity decay (SSD) at the regional scale. We find a considerable overlap of
      bird communities in the different land-uses (farmland, shrubland and oak forest)
      at the landscape scale. Analysis of the classic and countryside SAR show that
      specialist species are strongly related to their favourite habitat. Farmland and
      shrubland have higher regional SSD compared to oak forests. However, this is due
      to the opportunistic use of farmlands by generalist birds. Forest specialists
      display significant regional turnover in oak forest. Overall, the countryside-SAR
      model had a better fit to the data showing that habitat composition determines
      species richness across scales. Finally, we use the countryside-SAR model to
      forecast bird diversity under four scenarios of land-use change. Farmland
      abandonment scenarios show little impact on bird diversity as the model predicts
      that the complete loss of farmland is less dramatic, in terms of species
      diversity loss, than the disappearance of native Galicio-Portuguese oak forest.
      The affinities of species to non-preferred habitats suggest that bird communities
      can adapt to land-use changes derived from farmland abandonment. Based on model
      predictions we argue that rewilding may be a suitable management option for many
      European mountain areas. 

PMID- 24023893
TI  - Lrig2-deficient mice are protected against PDGFB-induced glioma.
AB  - BACKGROUND: The leucine-rich repeats and immunoglobulin-like domains (LRIG)
      proteins constitute an integral membrane protein family that has three members:
      LRIG1, LRIG2, and LRIG3. LRIG1 negatively regulates growth factor signaling, but
      little is known regarding the functions of LRIG2 and LRIG3. In oligodendroglial
      brain tumors, high expression of LRIG2 correlates with poor patient survival.
      Lrig1 and Lrig3 knockout mice are viable, but there have been no reports on Lrig2
      deficient mice to date. METHODOLOGY/PRINCIPAL FINDINGS: Lrig2-deficient mice were
      generated by the ablation of Lrig2 exon 12 (Lrig2E12). The Lrig2E12-/- mice
      showed a transiently reduced growth rate and an increased spontaneous mortality
      rate; 20-25% of these mice died before 130 days of age, with the majority of the
      deaths occurring before 50 days. Ntv-a transgenic mice with different Lrig2
      genotypes were transduced by intracranial injection with platelet-derived growth
      factor (PDGF) B-encoding replication-competent avian retrovirus (RCAS)-producing
      DF-1 cells. All injected Lrig2E12+/+ mice developed Lrig2 expressing
      oligodendroglial brain tumors of lower grade (82%) or glioblastoma-like tumors of
      higher grade (18%). Lrig2E12-/- mice, in contrast, only developed lower grade
      tumors (77%) or had no detectable tumors (23%). Lrig2E12-/- mouse embryonic
      fibroblasts (MEF) showed altered induction-kinetics of immediate-early genes Fos
      and Egr2 in response to PDGF-BB stimulation. However, Lrig2E12-/- MEFs showed no
      changes in Pdgfralpha or Pdgfrbeta levels or in levels of PDGF-BB-induced
      phosphorylation of Pdgfralpha, Pdgfrbeta, Akt, or extracellular signal-regulated
      protein kinases 1 and 2 (ERK1/2). Overexpression of LRIG1, but not of LRIG2,
      downregulated PDGFRalpha levels in HEK-293T cells. CONCLUSIONS: The phenotype of
      Lrig2E12-/- mice showed that Lrig2 was a promoter of PDGFB-induced glioma, and
      Lrig2 appeared to have important molecular and developmental functions that were
      distinct from those of Lrig1 and Lrig3.

PMID- 24023894
TI  - Cognitive declines precede and predict functional declines in aging and
      Alzheimer's disease.
AB  - OBJECTIVE: To investigate the temporal ordering of cognitive and functional
      declines separately in older adults with or without Alzheimer's disease (AD).
      DESIGN AND SETTING: A community-based longitudinal study of aging and dementia in
      Northern Manhattan (Washington Heights/Hamilton Heights Inwood Columbia Aging
      Project) and a multicenter, clinic-based longitudinal study of prevalent AD at
      Columbia University Medical Center, Johns Hopkins School of Medicine,
      Massachusetts General Hospital, and the Hopital de la Salpetriere in Paris,
      France (the Predictors Study). PARTICIPANTS: 3,443 initially non-demented older
      adults (612 with eventual incident dementia) and 517 patients with AD. MAIN
      OUTCOME MEASURES: Cognitive measures included the modified Mini-Mental State Exam
      and composite scores of memory and language derived from a standardized
      neuropsychological battery. Function was measured with the Blessed Dementia
      Rating Scale, completed by the participant (in the sample of non-demented older
      adults) or an informant (in the sample of prevalent AD patients). Data were
      analyzed with autoregressive cross-lagged panel analysis. RESULTS: Cognitive
      scores more consistently predicted subsequent functional abilities than vice
      versa in non-demented older adults, participants with eventual incident dementia,
      and patients with prevalent AD. CONCLUSIONS: Cognitive declines appear to precede
      and cause functional declines prior to and following dementia diagnosis.
      Standardized neuropsychological tests are valid predictors of later functional
      changes in both non-demented and demented older adults.

PMID- 24023895
TI  - MHC class II tetramers made from isolated recombinant alpha and beta chains
      refolded with affinity-tagged peptides.
AB  - Targeting CD4+ T cells through their unique antigen-specific, MHC class II
      restricted T cell receptor makes MHC class II tetramers an attractive strategy to
      identify, validate and manipulate these cells at the single cell level.
      Currently, generating class II tetramers is a specialized undertaking effectively
      limiting their use and emphasizing the need for improved methods of production.
      Using class II chains expressed individually in E. coli as versatile recombinant
      reagents, we have previously generated peptide-MHC class II monomers, but failed
      to generate functional class II tetramers. Adding a monomer purification
      principle based upon affinity-tagged peptides, we here provide a robust method to
      produce class II tetramers and demonstrate staining of antigen-specific CD4+ T
      cells. We also provide evidence that both MHC class II and T cell receptor
      molecules largely accept affinity-tagged peptides. As a general approach to class
      II tetramer generation, this method should support rational CD4+ T cell epitope
      discovery as well as enable specific monitoring and manipulation of CD4+ T cell
      responses. 

PMID- 24023896
TI  - Rapamycin enhances adenovirus-mediated cancer imaging and therapy in pre
      immunized murine hosts.
AB  - Tumor-specific adenoviral vectors comprise a fruitful gene-based diagnostic
      imaging and therapy research area for advanced stage of cancer, including
      metastatic disease. However, clinical translation of viral vectors has
      encountered considerable obstacles, largely due to host immune responses against
      the virus. Here, we explored the utilization of an immunosuppressant, rapamycin,
      to circumvent the anti-adenovirus immunity in immunocompetent murine prostate
      cancer models. Rapamycin diminished adenoviral-induced acute immune response by
      inhibiting NF-kappaB activation; it also reduced the scale and delayed the onset
      of inflammatory cytokine secretion. Further, we found that rapamycin abrogated
      anti-adenovirus antibody production and retarded the function of myeloid cells
      and lymphocytes that were activated upon viral administration in pre-immunized
      hosts. Thus, the co-administration of rapamycin prolonged and enhanced adenovirus
      delivered transgene expression in vivo, and thereby augmented the imaging
      capability of adenoviral vectors in both bioluminescent and positron emission
      tomography modalities. Furthermore, we showed that despite an excellent response
      of cancer cells to a cytotoxic gene therapeutic vector in vitro, only minimal
      therapeutic effects were observed in vivo in pre-immunized mice. However, when we
      combined gene therapy with transient immunosuppression, complete tumor growth
      arrest was achieved. Overall, transient immunosuppression by rapamycin was able
      to boost the diagnostic utility and therapeutic potentials of adenoviral vectors.

PMID- 24023898
TI  - Monitoring the status and trends of tropical forest terrestrial vertebrate
      communities from camera trap data: a tool for conservation.
AB  - Reducing the loss of biodiversity is key to ensure the future well being of the
      planet. Indicators to measure the state of biodiversity should come from primary
      data that are collected using consistent field methods across several sites,
      longitudinal, and derived using sound statistical methods that correct for
      observation/detection bias. In this paper we analyze camera trap data collected
      between 2008 and 2012 at a site in Costa Rica (Volcan Barva transect) as part of
      an ongoing tropical forest global monitoring network (Tropical Ecology Assessment
      and Monitoring Network). We estimated occupancy dynamics for 13 species of
      mammals, using a hierarchical modeling approach. We calculated detection
      corrected species richness and the Wildlife Picture Index, a promising new
      indicator derived from camera trap data that measures changes in biodiversity
      from the occupancy estimates of individual species. Our results show that 3 out
      of 13 species showed significant declines in occupancy over 5 years (lowland
      paca, Central American agouti, nine-banded armadillo). We hypothesize that
      hunting, competition and/or increased predation for paca and agouti might explain
      these patterns. Species richness and the Wildlife Picture Index are relatively
      stable at the site, but small herbivores that are hunted showed a decline in
      diversity of about 25%. We demonstrate the usefulness of longitudinal camera trap
      deployments coupled with modern statistical methods and advocate for the use of
      this approach in monitoring and developing global and national indicators for
      biodiversity change. 

PMID- 24023897
TI  - High "normal" blood glucose is associated with decreased brain volume and
      cognitive performance in the 60s: the PATH through life study.
AB  - CONTEXT: Type 2 diabetes is associated with cerebral atrophy, cognitive
      impairment and dementia. We recently showed higher glucose levels in the normal
      range not to be free of adverse effects and to be associated with greater
      hippocampal and amygdalar atrophy in older community-dwelling individuals free of
      diabetes. OBJECTIVE: This study aimed to determine whether blood glucose levels
      in the normal range (<6.1 mmol/L) were associated with cerebral volumes in
      structures other than the hippocampus and amygdale, and whether these glucose
      related regional volumes were associated with cognitive performance. DESIGN
      SETTING AND PARTICIPANTS: 210 cognitively healthy individuals (68-73 years)
      without diabetes, glucose intolerance or metabolic syndrome were assessed in the
      large, community-based Personality and Total Health Through Life (PATH) study.
      MAIN OUTCOME MEASURE: Baseline blood glucose levels in the normal range (3.2-6.1
      mmol/l) were used to determine regional brain volumes and associated cognitive
      function at wave 3. RESULTS: Higher blood glucose levels in the normal range were
      associated with lower grey/white matter regional volumes in the frontal cortices
      (middle frontal gyrus, inferior frontal gyrus precentral gyrus). Moreover,
      identified cerebral regions were associated with poorer cognitive performance and
      the structure-function associations were gender specific to men. CONCLUSION:
      These findings stress the need to re-evaluate what is considered as healthy blood
      glucose levels, and consider the role of higher normal blood glucose as a risk
      factor for cerebral health, cognitive function and dementia. A better lifetime
      management of blood glucose levels may contribute to improved cerebral and
      cognitive health in later life and possibly protect against dementia.

PMID- 24023899
TI  - Profiling of genes related to cross protection and competition for NbTOM1 by HLSV
      and TMV.
AB  - Cross protection is the phenomenon through which a mild strain virus suppresses
      symptoms induced by a closely related severe strain virus in infected plants.
      Hibiscus latent Singapore virus (HLSV) and Tobacco mosaic virus (TMV) are species
      within the genus tobamovirus. HLSV can protect Nicotianabenthamiana against TMV
      U1 strain, resulting in mild symptoms instead of severe systemic necrosis. The
      mechanism of cross protection between HLSV and TMV is unknown. In the past, some
      researchers suggest that the protecting virus strain might occupy virus-specific
      replication sites within a cell leaving no room for the challenge virus.
      Quantitative real-time RT-PCR was performed to detect viral RNA levels during
      cross protection. HLSV accumulation increased in cross protected plants compared
      with that of single HLSV infected plants, while TMV decreased in cross protected
      plants. This suggests that there is a competition for host factors between HLSV
      and TMV for replication. To investigate the mechanism under the cross protection
      between HLSV and TMV, microarray analysis was conducted to examine the
      transcriptional levels of global host genes during cross protection, using
      Tobacco Gene Expression Microarray, 4 x 44 k slides. The transcriptional level of
      some host genes corresponded to accumulation level of TMV. Some host genes were
      up-regulated only by HLSV. Tobamovirus multiplication gene 1 (TOM1), essential
      for tobamovirus multiplication, was involved in competition for replication by
      HLSV and TMV during cross protection. Both HLSV and TMV accumulation decreased
      when NbTOM1 was silenced. A large quantity of HLSV resulted in decreased TMV
      accumulation in HLSV+TMV (100:1) co-infection. These results indicate that host
      genes involved in the plant defense response and virus multiplication are up
      regulated by challenge virus TMV but not by protecting virus HLSV during cross
      protection.

PMID- 24023900
TI  - Dynamics of forest malaria transmission in Balaghat district, Madhya Pradesh,
      India.
AB  - BACKGROUND: An epidemiological and entomological study was carried out in
      Balaghat district, Madhya Pradesh, India to understand the dynamics of forest
      malaria transmission in a difficult and hard to reach area where indoor residual
      spray and insecticide treated nets were used for vector control. METHODS: This
      community based cross-sectional study was undertaken from January 2010 to
      December 2012 in Baihar and Birsa Community Health Centres of district Balaghat
      for screening malaria cases. Entomological surveillance included indoor resting
      collections, pyrethrum spray catches and light trap catches. Anophelines were
      assayed by ELISA for detection of Plasmodium circumsporozoite protein. FINDINGS:
      Plasmodium falciparum infection accounted for >80% of all infections. P. vivax
      16.5%, P. malariae 0.75% and remaining were mixed infections of P. falciparum, P.
      vivax and P. malariae. More than, 30% infections were found in infants under 6
      months of age. Overall, an increasing trend in malaria positivity was observed
      from 2010 to 2012 (chi-square for trend  =  663.55; P<0.0001). Twenty five
      Anopheles culicifacies (sibling species C, D and E) were positive for
      circumsporozoite protein of P. falciparum (44%) and P. vivax (56%). Additionally,
      2 An. fluviatilis, were found positive for P. falciparum and 1 for P. vivax
      (sibling species S and T). An. fluviatilis sibling species T was found as vector
      in forest villages for the first time in India. CONCLUSION: These results showed
      that the study villages are experiencing almost perennial malaria transmission
      inspite of indoor residual spray and insecticide treated nets. Therefore, there
      is a need for new indoor residual insecticides which has longer residual life or
      complete coverage of population with long lasting insecticide treated nets or
      both indoor residual spray and long lasting bed nets for effective vector
      control. There is a need to undertake a well designed case control study to
      evaluate the efficacy of these interventions.

PMID- 24023901
TI  - DEAD box protein DDX1 regulates cytoplasmic localization of KSRP.
AB  - mRNA decay mediated by the AU-rich elements (AREs) is one of the most studied
      post-transcriptional mechanisms and is modulated by ARE-binding proteins (ARE
      BPs). To understand the regulation of K homology splicing regulatory protein
      (KSRP), a decay-promoting ARE-BP, we purified KSRP protein complexes and
      identified an RNA helicase, DDX1. We showed that down-regulation of DDX1
      expression elevated cytoplasmic levels of KSRP and facilitated ARE-mediated mRNA
      decay. Association of KSRP with 14-3-3 proteins, that are predominately located
      in the cytoplasm, increased upon reduction of DDX1. We also demonstrated that
      KSRP associated with DDX1 or 14-3-3, but not both. These observations indicate
      that subcellular localization of KSRP is regulated by competing interactions with
      DDX1 or 14-3-3. 

PMID- 24023902
TI  - Altered endothelin receptor expression and affinity in spontaneously hypertensive
      rat cerebral and coronary arteries.
AB  - BACKGROUND: Hypertension is associated with arterial hyperreactivity, and
      endothelin (ET) receptors are involved in vascular pathogenesis. The present
      study was performed to examine the hypothesis that ET receptors were altered in
      cerebral and coronary arteries of spontaneously hypertensive rats (SHR).
      METHODOLOGY/PRINCIPAL FINDINGS: Cerebral and coronary arteries were removed from
      SHR. Vascular contraction was recorded using a sensitive myograph system. Real
      time PCR and Western blotting were used to quantify mRNA and protein expression
      of receptors and essential MAPK pathway molecules. The results demonstrated that
      both ETA and ETB receptor-mediated contractile responses in SHR cerebral arteries
      were shifted to the left in a nonparallel manner with increased maximum
      contraction compared with Wistar-Kyoto (WKY) rats. In SHR coronary arteries, the
      ETA receptor-mediated contraction curve was shifted to the left in parallel with
      an increased pEC50 compared with the arteries in WKY rats. There was no
      significant increase in ETB receptor-mediated contraction in SHR coronary
      arteries. ETA receptor mRNA and protein expression was increased in SHR cerebral
      arteries compared with the arteries in WKY rats. However, ETA receptor mRNA and
      protein levels in coronary arteries and ETB receptor protein levels in cerebral
      and coronary arteries remained unchanged in SHR compared with WKY rats.
      Meanwhile, phosphorylated ERK1/2 protein was significantly increased in SHR brain
      and heart vessels. CONCLUSIONS/SIGNIFICANCE: In SHR cerebral arteries, ETA
      receptor expression was upregulated. ETA receptor affinity was increased in
      coronary arteries, and ETB receptor affinity was increased in cerebral arteries.
      The ERK1/2 activation may be involved in the receptor alterations.

PMID- 24023903
TI  - Insights into the cross-immunity mechanism within effector families of bacteria
      type VI secretion system from the structure of StTae4-EcTai4 complex.
AB  - The Gram-negative bacteria type VI secretion system (T6SS) has been found to play
      an important role in interbacterial competition, biofilm formation and many other
      virulence-related processes. The bacteria harboring T6SS inject the effectors
      into their recipient's cytoplasm or periplasm to kill them and meanwhile, to
      avoid inhibiting itself, the cognate immunity proteins were produced to acts as
      the effector inhibitor. Tae4 (type VI amidase effector 4) and Tai4 (type VI
      amidase immunity 4) are newly identified T6SS effector-immunity (EI) pairs. We
      have recently solved the structures of StTae4-Tai4 and EcTae4-Tai4 complexes from
      the human pathogens Salmonella typhimurium and Enterobacter cloacae,
      respectively. It is very interesting and important to discover whether there is
      cross-neutralization between St- and EcTai4 and whether their effector inhibition
      mechanism is conserved. Here, we determined the crystal structure of StTae4 in
      complex with EcTai4. The solution conformation study revealed it is a compact
      heterotetramer that consists of an EcTai4 homodimer binding two StTae4 molecules
      in solution, different from that in crystal. A remarkable shift can be observed
      in both the flexible winding loop of StTae4 and protruding loop of EcTai4 and
      disulfide bonds are formed to stabilize their overall conformations. The in vitro
      and in vivo interactions studies showed EcTai4 can efficiently rescue the cells
      from the toxicity of its cognate effectors StTae4, but can not neutralize the
      toxic activities of the effectors from other families. These findings provide
      clear structural evidence to support the previous observation of cross-immunity
      within T6SS families and provide a basis for understanding their important roles
      in polymicrobial environments. 

PMID- 24023904
TI  - Identification of appropriate reference genes for human mesenchymal cells during
      expansion and differentiation.
AB  - BACKGROUND: Quantitative real time polymerase chain reaction (qPCR) is an
      extremely powerful technique for monitoring gene expression. The quantity of the
      messenger ribonucleic acids (mRNA) of interest should be normalized using a
      reference gene, in order to avoid unreliable results originated by the obtained
      RNA quality and quantity, manipulation errors and inhibitory contaminants. A
      reference gene is any gene that is stably and consistently expressed under the
      conditions being studied. Completely false data can be generated if a reference
      gene is not chosen adequately. RESULTS: In the present study, we compared
      expression levels of five putative reference genes (HPRT1, ACTB, GAPDH, RPL13A
      and B2M) in primary cultures of four different human cells: mesenchymal stromal
      cells obtained from bone marrow, adipose tissue or umbilical cord Whartons Jelly,
      and dermal fibroblasts, under different expansion and differentiation conditions.
      We observed that reference genes are not the same for different cells under the
      same culture conditions. CONCLUSION: Most stable reference genes under our
      experimental conditions were: RPL13A for adipose tissue- and Whartons Jelly
      derived mesenchymal stromal cells, and HPRT1 for bone marrow-derived mesenchymal
      stromal cells and dermal fibroblasts. ACTB was the most unstable gene when
      evaluating adipose tissue- and Whartons Jelly-derived mesenchymal stromal cells,
      whilst GAPDH and B2M were the most unstable genes for bone marrow-derived
      mesenchymal stromal cells and dermal fibroblasts, respectively.

PMID- 24023905
TI  - Sexual knowledge, attitudes and practices of female undergraduate students in
      Wuhan, China: the only-child versus students with siblings.
AB  - OBJECTIVES: This study explored sexual knowledge, attitudes and practices of
      female only-child undergraduates and made a comparison with students with
      siblings. METHODS: Anonymously completed questionnaires were received from 4,769
      female undergraduates, recruited using randomized cluster sampling by type of
      university and students' major and grade. Multivariate logistic regression was
      used to assess the effects of only-child on sexual knowledge, attitudes and
      practices among female undergraduates. RESULTS: Of 4,769 female undergraduate
      students, 41.0% were only-child and 59.0% were students with siblings. Compared
      with students with siblings, only-child students scored higher on sex-related
      knowledge, were more inclined to agree with premarital sex, multiple sex
      partners, one-night stands, extramarital lovers and homosexuality, and were more
      likely to have a boyfriend and experience sexual intercourse (73.6% vs. 61.4%;
      24.0% vs. 14.0%). Only-children were less likely to experience coercion at first
      sex and have first sexual intercourse with men not their "boyfriends" than
      children with siblings (3.3% vs. 6.4%; 20.7% vs. 28.8%). There were no
      significant differences on other risky sexual behaviors (e.g. multiple sex
      partners and inconsistent condom use) between the only-child students and
      students with siblings. CONCLUSIONS: Sexual knowledge, attitudes and some
      practices of only-child female undergraduates were different from students with
      siblings. Intervention should be designed according to different requirements of
      only-children and non-only-children.

PMID- 24023906
TI  - The power of the claw.
AB  - Scratches on bones have routinely been attributed to tooth marks (a predominantly
      untested speculation), ignoring the effects of claws, perhaps because of the
      general assumption that claws are too soft to damage bone. However, some
      pathologies appears to be more compatible with claw rather than tooth impacts.
      Therefore, it is critical to determine if the claws of any animal are capable of
      scratching into the surface of any bone--a test and proof of concept. A tiger
      enrichment program was used to document actual bone damage unequivocally caused
      by claws, by assuring that the tiger had access to bones only by using its paws
      (claws). The spectrum of mechanisms causing bone damage was expanded by
      evidentiary analysis of claw-induced pathology. While static studies suggested
      that nails/claws could not disrupt bone, specific tiger enrichment activities
      documented that bones were susceptible to damage from the kinetic energy effect
      of the striking claw. This documents an expanded differential consideration for
      scratch marks on bone and evidences the power of the claw.

PMID- 24023908
TI  - Variation in thermal performance of a widespread pathogen, the amphibian chytrid
      fungus Batrachochytrium dendrobatidis.
AB  - Rates of growth and reproduction of the pathogens that cause emerging infectious
      diseases can be affected by local environmental conditions; these conditions can
      thus influence the strength and nature of disease outbreaks. An understanding of
      these relationships is important for understanding disease ecology and developing
      mitigation strategies. Widespread emergence of the fungal disease
      chytridiomycosis has had devastating effects on amphibian populations. The
      causative pathogen, Batrachochytriumdendrobatidis (Bd), is sensitive to
      temperature, but its thermal tolerances are not well studied. We examined the
      thermal responses of three Bd isolates collected across a latitudinal gradient in
      eastern Australia. Temperature affected all aspects of Bd growth and reproduction
      that we measured, in ways that often differed among Bd isolates. Aspects of
      growth, reproduction, and their relationships to temperature that differed among
      isolates included upper thermal maxima for growth (26, 27, or 28  degrees C,
      depending on the isolate), relationships between zoospore production and
      temperature, and zoospore activity and temperature. Two isolates decreased
      zoospore production as temperature increased, whereas the third isolate was less
      fecund overall, but did not show a strong response to temperature until reaching
      the upper limit of its thermal tolerance. Our results show differentiation in
      life-history traits among isolates within Australia, suggesting that the pathogen
      may exhibit local adaptation. An understanding of how environmental temperatures
      can limit pathogens by constraining fitness will enhance our ability to assess
      pathogen dynamics in the field, model pathogen spread, and conduct realistic
      experiments on host susceptibility and disease transmission.

PMID- 24023907
TI  - Metagenomic profiling reveals lignocellulose degrading system in a microbial
      community associated with a wood-feeding beetle.
AB  - The Asian longhorned beetle (Anoplophoraglabripennis) is an invasive, wood-boring
      pest that thrives in the heartwood of deciduous tree species. A large impediment
      faced by A. glabripennis as it feeds on woody tissue is lignin, a highly
      recalcitrant biopolymer that reduces access to sugars and other nutrients locked
      in cellulose and hemicellulose. We previously demonstrated that lignin,
      cellulose, and hemicellulose are actively deconstructed in the beetle gut and
      that the gut harbors an assemblage of microbes hypothesized to make significant
      contributions to these processes. While lignin degrading mechanisms have been
      well characterized in pure cultures of white rot basidiomycetes, little is known
      about such processes in microbial communities associated with wood-feeding
      insects. The goals of this study were to develop a taxonomic and functional
      profile of a gut community derived from an invasive population of larval A.
      glabripennis collected from infested host trees and to identify genes that could
      be relevant for the digestion of woody tissue and nutrient acquisition. To
      accomplish this goal, we taxonomically and functionally characterized the A.
      glabripennis midgut microbiota through amplicon and shotgun metagenome sequencing
      and conducted a large-scale comparison with the metagenomes from a variety of
      other herbivore-associated communities. This analysis distinguished the A.
      glabripennis larval gut metagenome from the gut communities of other herbivores,
      including previously sequenced termite hindgut metagenomes. Genes encoding
      enzymes were identified in the A. glabripennis gut metagenome that could have key
      roles in woody tissue digestion including candidate lignin degrading genes
      (laccases, dye-decolorizing peroxidases, novel peroxidases and beta-etherases),
      36 families of glycoside hydrolases (such as cellulases and xylanases), and genes
      that could facilitate nutrient recovery, essential nutrient synthesis, and
      detoxification. This community could serve as a reservoir of novel enzymes to
      enhance industrial cellulosic biofuels production or targets for novel control
      methods for this invasive and highly destructive insect. 

PMID- 24023909
TI  - Quantitation of gene expression in formaldehyde-fixed and fluorescence-activated
      sorted cells.
AB  - Fluorescence-activated cell sorting (FACS) is a sensitive and valuable technique
      to characterize cellular subpopulations and great advances have been made using
      this approach. Cells are often fixed with formaldehyde prior to the sorting
      process to preserve cell morphology and maintain the expression of surface
      molecules, as well as to ensure safety in the sorting of infected cells. It is
      widely recognized that formaldehyde fixation alters RNA and DNA structure and
      integrity, thus analyzing gene expression in these cells has been difficult. We
      therefore examined the effects of formaldehyde fixation on the stability and
      quantitation of nucleic acids in cell lines, primary leukocytes and also cells
      isolated from SIV-infected pigtailed macaques. We developed a method to extract
      RNA from fixed cells that yielded the same amount of RNA as our common method of
      RNA isolation from fresh cells. Quantitation of RNA by RT-qPCR in fixed cells was
      not always comparable with that in unfixed cells. In comparison, when RNA was
      measured by the probe-based NanoString system, there was no significant
      difference in RNA quantitation. In addition, we demonstrated that quantitation of
      proviral DNA in fixed cells by qPCR is comparable to that in unfixed cells when
      normalized by a single-copy cellular gene. These results provide a systematic
      procedure to quantitate gene expression in cells that have been fixed with
      formaldehyde and sorted by FACS. 

PMID- 24023910
TI  - Transcriptome profiling reveals Th17-like immune responses induced in zebrafish
      bath-vaccinated with a live attenuated Vibrio anguillarum.
AB  - BACKGROUND: A candidate vaccine, live attenuated Vibrio anguillarum developed in
      our laboratory could prevent vibriosis of fish resulted from V. anguillarum and
      V. alginolyticus. To elucidate the molecular mechanisms underlying the vaccine
      protection, we used microarray technology to compare the spleen transcriptomes of
      bath-vaccinated and unvaccinated zebrafish at 28 days post vaccination. PRINCIPAL
      FINDINGS: A total of 2164 genes and transcripts were differentially expressed,
      accounting for 4.9% of all genes represented on the chip. In addition to iron
      metabolism related to the innate immunity and the signaling pathways, these
      differentially expressed genes also involved in the adaptive immunity, mainly
      including the genes associated with B and T cells activation, proliferation and
      expansion. Transcription profiles of Th17-related transcription factors,
      cytokines and cytokine receptors during 35 days post-vaccination implied that
      Th17 cells be activated in bath-vaccinated zebrafish. CONCLUSION/SIGNIFICANCE:
      The transcriptome profiling with microarray revealed the Th17-like immune
      response to bath-vaccination with the live attenuated V. anguillarum in
      zebrafish.

PMID- 24023911
TI  - Flavonoid rutin increases thyroid iodide uptake in rats.
AB  - Thyroid iodide uptake through the sodium-iodide symporter (NIS) is not only an
      essential step for thyroid hormones biosynthesis, but also fundamental for the
      diagnosis and treatment of different thyroid diseases. However, part of patients
      with thyroid cancer is refractory to radioiodine therapy, due to reduced ability
      to uptake iodide, which greatly reduces the chances of survival. Therefore,
      compounds able to increase thyroid iodide uptake are of great interest. It has
      been shown that some flavonoids are able to increase iodide uptake and NIS
      expression in vitro, however, data in vivo are lacking. Flavonoids are
      polyhydroxyphenolic compounds, found in vegetables present in human diet, and
      have been shown not only to modulate NIS, but also thyroperoxidase (TPO), the key
      enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect
      in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some
      flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids
      tested, rutin was the only one able to increase thyroid iodide uptake, so we
      decided to evaluate the effect of this flavonoid on some aspects of thyroid
      hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4
      and T3 without changes in serum thyrotropin (TSH), and significantly increased
      hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased
      liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid
      iodide uptake probably due to the increment of NIS expression, which might be
      secondary to increased response to TSH, since TSH receptor expression was
      increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy,
      since this flavonoid increased thyroid iodide uptake without greatly affecting
      thyroid function. 

PMID- 24023912
TI  - The chicken HS4 insulator element does not protect the H19 ICR from differential
      DNA methylation in yeast artificial chromosome transgenic mouse.
AB  - Mono-allelic expression at the mouse IGF2/H19 locus is controlled by differential
      allelic DNA methylation of the imprinting control region (ICR). Because a
      randomly integrated H19 ICR fragment, when incorporated into the genome of
      transgenic mice (TgM), was allele-specifically methylated in somatic, but not in
      germ cells, it was suggested that allele-discriminating epigenetic signature, set
      within or somewhere outside of the Tg H19 ICR fragment in germ cells, was later
      translated into a differential DNA methylation pattern. To test if the chicken
      beta-globin HS4 (cHS4) chromatin insulator might interfere with methylation
      imprinting establishment at the H19 ICR, we inserted the H19 ICR fragment,
      flanked by a set of floxed cHS4 core sequences, into a human beta-globin locus
      YAC and generated TgM (insulated ICR' TgM). As controls, the cHS4 sequences were
      removed from one side (5'HS4-deleted ICR') or both sides (pseudo-WT ICR') of the
      insulated ICR' by in vivo cre-loxP recombination. The data show that while
      maternally inherited transgenic H19 ICR was not methylated in insulated ICR' TgM,
      it was significantly methylated upon paternal transmission, though the level was
      lower than in the pseudo-WT ICR' control. Because this reduced level of
      methylation was also observed in the 5'HS4-deleted ICR' TgM, we speculate that
      the phenotype is due to VEZF1-dependent demethylation activity, rather than the
      insulator function, borne in cHS4. Collectively, although we cannot rule out the
      possibility that cHS4 is incapable of blocking an allele-discriminating signal
      from outside of the transgene, the epigenetic signature appears to be marked
      intrinsically within the H19 ICR. 

PMID- 24023913
TI  - Evaluating detection limits of next-generation sequencing for the surveillance
      and monitoring of international marine pests.
AB  - Most surveillance programmes for marine invasive species (MIS) require
      considerable taxonomic expertise, are laborious, and are unable to identify
      species at larval or juvenile stages. Therefore, marine pests may go undetected
      at the initial stages of incursions when population densities are low. In this
      study, we evaluated the ability of the benchtop GS JuniorTM 454 pyrosequencing
      system to detect the presence of MIS in complex sample matrices. An initial in
      silico evaluation of the mitochondrial cytochrome c oxidase subunit I (COI) and
      the nuclear small subunit ribosomal DNA (SSU) genes, found that multiple primer
      sets (targeting a ca. 400 base pair region) would be required to obtain species
      level identification within the COI gene. In contrast a single universal primer
      set was designed to target the V1-V3 region of SSU, allowing simultaneous PCR
      amplification of a wide taxonomic range of MIS. To evaluate the limits of
      detection of this method, artificial contrived communities (10 species from 5
      taxonomic groups) were created using varying concentrations of known DNA samples
      and PCR products. Environmental samples (water and sediment) spiked with one or
      five 160 hr old Asterias amurensis larvae were also examined. Pyrosequencing was
      able to recover DNA/PCR products of individual species present at greater than
      0.64% abundance from all tested contrived communities. Additionally, single A.
      amurensis larvae were detected from both water and sediment samples despite the
      co-occurrence of a large array of environmental eukaryotes, indicating an
      equivalent sensitivity to quantitative PCR. NGS technology has tremendous
      potential for the early detection of marine invasive species worldwide. 

PMID- 24023914
TI  - Lipidomic profiling of Saccharomyces cerevisiae and Zygosaccharomyces bailii
      reveals critical changes in lipid composition in response to acetic acid stress.
AB  - When using microorganisms as cell factories in the production of bio-based fuels
      or chemicals from lignocellulosic hydrolysate, inhibitory concentrations of
      acetic acid, released from the biomass, reduce the production rate. The
      undissociated form of acetic acid enters the cell by passive diffusion across the
      lipid bilayer, mediating toxic effects inside the cell. In order to elucidate a
      possible link between lipid composition and acetic acid stress, the present study
      presents detailed lipidomic profiling of the major lipid species found in the
      plasma membrane, including glycerophospholipids, sphingolipids and sterols, in
      Saccharomyces cerevisiae (CEN.PK 113_7D) and Zygosaccharomyces bailii (CBS7555)
      cultured with acetic acid. Detailed physiological characterization of the
      response of the two yeasts to acetic acid has also been performed in aerobic
      batch cultivations using bioreactors. Physiological characterization revealed, as
      expected, that Z. bailii is more tolerant to acetic acid than S. cerevisiae. Z.
      bailii grew at acetic acid concentrations above 24 g L(-1), while limited growth
      of S. cerevisiae was observed after 11 h when cultured with only 12 g L(-1)
      acetic acid. Detailed lipidomic profiling using electrospray ionization, multiple
      reaction-monitoring mass spectrometry (ESI-MRM-MS) showed remarkable changes in
      the glycerophospholipid composition of Z. bailii, including an increase in
      saturated glycerophospholipids and considerable increases in complex
      sphingolipids in both S. cerevisiae (IPC 6.2*, MIPC 9.1*, M(IP)2C 2.2*) and Z.
      bailii (IPC 4.9*, MIPC 2.7*, M(IP)2C 2.7*), when cultured with acetic acid. In
      addition, the basal level of complex sphingolipids was significantly higher in Z.
      bailii than in S. cerevisiae, further emphasizing the proposed link between lipid
      saturation, high sphingolipid levels and acetic acid tolerance. The results also
      suggest that acetic acid tolerance is associated with the ability of a given
      strain to generate large rearrangements in its lipid profile. 

PMID- 24023915
TI  - Plastid genome sequence of a wild woody oil species, Prinsepia utilis, provides
      insights into evolutionary and mutational patterns of Rosaceae chloroplast
      genomes.
AB  - BACKGROUND: Prinsepiautilis Royle is a wild woody oil species of Rosaceae that
      yields edible oil which has been proved to possess particular benefits for human
      health and medical therapy. However, the lack of bred varieties has largely
      impeded exploiting immense potentials for high quality of its seed oil. It is
      urgently needed to enlarge the knowledge of genetic basis of the species and
      develop genetic markers to enhance modern breeding programs. RESULTS: Here we
      reported the complete chloroplast (cp) genome of 156,328 bp. Comparative cp
      sequence analyses of P. utilis along with other four Rosaceae species resulted in
      similar genome structures, gene orders, and gene contents. Contraction/expansion
      of inverted repeat regions (IRs) explained part of the length variation in the
      Rosaceae cp genomes. Genome sequence alignments revealed that nucleotide
      diversity was associated with AT content, and large single copy regions (LSC) and
      small single copy regions (SSC) harbored higher sequence variations in both
      coding and non-coding regions than IRs. Simple sequence repeats (SSRs) were
      detected in the P. utilis and compared with those of the other four Rosaceae cp
      genomes. Almost all the SSR loci were composed of A or T, therefore it might
      contribute to the A-T richness of cp genomes and be associated with AT biased
      sequence variation. Among all the protein-coding genes, ycf1 showed the highest
      sequence divergence, indicating that it could accomplish the discrimination of
      species within Rosaceae as well as within angiosperms better than other genes.
      CONCLUSIONS: With the addition of this new sequenced cp genome, high nucleotide
      substitution rate and abundant deletions/insertions were observed, suggesting a
      greater genomic dynamics than previously explored in Rosaceae. The availability
      of the complete cp genome of P. utilis will provide chloroplast markers and
      genetic information to better enhance the conservation and utilization of this
      woody oil plant.

PMID- 24023916
TI  - Depletion of CD4+ CD25+ regulatory T cells promotes CCL21-mediated antitumor
      immunity.
AB  - CCL21 is known to attract dendritic cells (DCs) and T cells that may reverse
      tumor-mediated immune suppression. The massive infiltration of tumors by
      regulatory T cells (Tregs) prevents the development of a successful helper immune
      response. In this study, we investigated whether elimination of CD4(+) CD25(+)
      Tregs in the tumor microenvironment using anti-CD25 monoclonal antibodies (mAbs)
      was capable of enhancing CCL21-mediated antitumor immunity in a mouse
      hepatocellular carcinoma (HCC) model. We found that CCL21 in combination with
      anti-CD25 mAbs (PC61) resulted in improved antitumor efficacy and prolonged
      survival, not only inhibited tumor angiogenesis and cell proliferation, but also
      led to significant increases in the frequency of CD4(+), CD8(+) T cells and
      CD11c(+) DCs within the tumor, coincident with marked induction of tumor-specific
      CD8(+) cytotoxic T lymphocytes (CTLs) at the local tumor site. The intratumoral
      immune responses were accompanied by the enhanced elaboration of IL-12 and IFN
      gamma, but reduced release of the immunosuppressive mediators IL-10 and TGF
      beta1. The results indicated that depletion of Tregs in the tumor
      microenvironment could enhance CCL21-mediated antitumor immunity, and CCL21
      combined with anti-CD25 mAbs may be a more effective immunotherapy to promote
      tumor rejection. 

PMID- 24023917
TI  - Human Melanoma cells over-express extracellular matrix 1 (ECM1) which is
      regulated by TFAP2C.
AB  - Extracellular matrix 1 (ECM1) is over-expressed in multiple epithelial
      malignancies. However, knowledge regarding the expression of ECM1 in melanomas
      and the mechanisms of ECM1 regulation is limited. In this study, we found that
      ECM1 is over-expressed in several melanoma cell lines, when compared to primary
      melanocytes, and furthermore, that ECM1 expression paralleled that of TFAP2C
      levels in multiple cell lines. Knockdown of TFAP2C in the A375 cell line with
      siRNA led to a reduction in ECM1 expression, and upregulation of TFAP2C with
      adenoviral vectors in the WM793 cell line resulted in ECM1 upregulation.
      Utilizing 5' RACE to identify transcription start sites (TSS) and luciferase
      reporter assays in the ECM1-overexpressing A375 cell line, we identified the
      minimal promoter region of human ECM1 and demonstrate that an approximately 100bp
      fragment upstream of the TSS containing a TATA box and binding sites for AP1, SP1
      and Ets is sufficient for promoter activity. Chromatin immunoprecipitation and
      direct sequencing (ChIP-seq) for TFAP2C in the A375 cell line identified an AP2
      regulatory region in the promoter of the ECM1 gene. Gelshift assays further
      confirmed binding of TFAP2C to this site. ECM1 knockdown reduces melanoma cell
      attachment and is consistent with findings that ECM1 overexpression has been
      associated with a poor prognosis. Our investigations show an as yet unrecognized
      role for TFAP2C in melanoma via its regulation of ECM1. 

PMID- 24023918
TI  - Whole transcriptome sequencing enables discovery and analysis of viruses in
      archived primary central nervous system lymphomas.
AB  - Primary central nervous system lymphomas (PCNSL) have a dramatically increased
      prevalence among persons living with AIDS and are known to be associated with
      human Epstein Barr virus (EBV) infection. Previous work suggests that in some
      cases, co-infection with other viruses may be important for PCNSL pathogenesis.
      Viral transcription in tumor samples can be measured using next generation
      transcriptome sequencing. We demonstrate the ability of transcriptome sequencing
      to identify viruses, characterize viral expression, and identify viral variants
      by sequencing four archived AIDS-related PCNSL tissue samples and analyzing raw
      sequencing reads. EBV was detected in all four PCNSL samples and cytomegalovirus
      (CMV), JC polyomavirus (JCV), and HIV were also discovered, consistent with
      clinical diagnoses. CMV was found to express three long non-coding RNAs recently
      reported as expressed during active infection. Single nucleotide variants were
      observed in each of the viruses observed and three indels were found in CMV. No
      viruses were found in several control tumor types including 32 diffuse large B
      cell lymphoma samples. This study demonstrates the ability of next generation
      transcriptome sequencing to accurately identify viruses, including DNA viruses,
      in solid human cancer tissue samples. 

PMID- 24023919
TI  - Luciferase reporter gene assay on human, murine and rat histamine H4 receptor
      orthologs: correlations and discrepancies between distal and proximal readouts.
AB  - The investigation of the (patho)physiological role of the histamine H4 receptor
      (H4R) and its validation as a possible drug target in translational animal models
      are compromised by distinct species-dependent discrepancies regarding potencies
      and receptor subtype selectivities of the pharmacological tools. Such differences
      were extremely pronounced in case of proximal readouts, e. g. [(32)P]GTPase or
      [(35)S]GTPgammaS binding assays. To improve the predictability of in vitro
      investigations, the aim of this study was to establish a reporter gene assay for
      human, murine and rat H4Rs, using bioluminescence as a more distal readout. For
      this purpose a cAMP responsive element (CRE) controlled luciferase reporter gene
      assay was established in HEK293T cells, stably expressing the human (h), the
      mouse (m) or the rat (r) H4R. The potencies and efficacies of 23 selected ligands
      (agonists, inverse agonists and antagonists) were determined and compared with
      the results obtained from proximal readouts. The potencies of the examined
      ligands at the human H4R were consistent with reported data from [(32)P]GTPase or
      [(35)S]GTPgammaS binding assays, despite a tendency toward increased intrinsic
      efficacies of partial agonists. The differences in potencies of individual
      agonists at the three H4R orthologs were generally less pronounced compared to
      more proximal readouts. In conclusion, the established reporter gene assay is
      highly sensitive and reliable. Regarding discrepancies compared to data from
      functional assays such as [(32)P]GTPase and [(35)S]GTPgammaS binding, the readout
      may reflect multifactorial causes downstream from G-protein activation, e.g.
      activation/amplification of or cross-talk between different signaling pathways. 

PMID- 24023920
TI  - Expression of the memory marker CD45RO on helper T cells in macaques.
AB  - BACKGROUND: In humans it has been reported that a major site of the latent
      reservoir of HIV is within CD4+ T cells expressing the memory marker CD45RO,
      defined by the mAb UCHL1. There are conflicting reports regarding the expression
      of this antigen in macaques, the most relevant animal species for studying HIV
      pathogenesis and testing new therapies. There is now a major effort to eradicate
      HIV reservoirs and cure the infection. One approach is to eliminate subsets of
      cells housing the latent reservoir, using UCHL1 to target these cells. So that
      such studies may be performed in macaques, it is essential to determine
      expression of CD45RO. METHODS: We have used immunofluorescence and flow cytometry
      to study cell surface expression of CD45RO on lymphocytes from PBMC, lymphoid,
      and GI organs of rhesus, pigtailed, and cynomolgus macaques. Both direct and
      indirect immunofluorescence experiments were performed. FINDINGS: CD45RO is
      expressed on a subset of CD4+ lymphocytes of all pigtailed, a fraction of rhesus,
      and neither of the cynomolgus macaques studied. The binding of UCHL1 to macaque
      cells was of lower avidity than to human cells. This could be overcome by forming
      UCHL1 multimers. Directly conjugating fluors to UCHL1 can inhibit UCHL1 binding
      to macaque cells. Patterns of UCHL1 expression differ somewhat in macaques and
      humans, and from that of other memory markers often used in macaques.
      CONCLUSIONS: CD45RO, defined with mAb UCHL1, is well expressed on CD4+ cells in
      pigtailed macaques. Using tissues recovered from latently infected pigtailed
      macaques we are determining whether UCHL1, or other memory markers, can define
      the cellular locus of the reservoir. The low avidity of this interaction could
      limit the utility of UCHL1, in its conventional form, to eliminate cells in vivo
      and test this approach in macaque models of HIV infection.

PMID- 24023921
TI  - Simultaneous inhibition of rhamnolipid and polyhydroxyalkanoic acid synthesis and
      biofilm formation in Pseudomonas aeruginosa by 2-bromoalkanoic acids: effect of
      inhibitor alkyl-chain-length.
AB  - Pseudomonas aeruginosa, an opportunistic human pathogen is known to synthesize
      rhamnolipid and polyhydroxyalkanoic acid (PHA) of which the acyl-group precursors
      (e.g., (R)-3-hydroxydecanoic acid) are provided through RhlA and PhaG enzyme,
      respectively, which have 57% gene sequence homology. The inhibitory effect of
      three 2-bromo-fatty acids of 2-bromohexanoic acid (2-BrHA), 2-bromooctanoic acid
      (2-BrOA) and 2-bromodecanoic acid (2-BrDA) was compared to get an insight into
      the biochemical nature of their probable dual inhibition against the two enzymes.
      The 2-bromo-compounds were found to inhibit rhamnolipid and PHA synthesis
      simultaneously in alkyl-chain-length dependent manner at several millimolar
      concentrations. The separate and dual inhibition of the RhlA and PhaG pathway by
      the 2-bromo-compounds in the wild-type cells was verified by investigating their
      inhibitory effects on the rhamnolipid and PHA synthesis in P. aeruginosa
      DeltaphaG and DeltarhlA mutants. Unexpectedly, the order of inhibition strength
      was found 2-BrHA (>=90% at 2 mM) > 2-BrOA > 2-BrDA, equally for all of the
      rhamnolipids and PHA synthesis, swarming motility and biofilm formation. We
      suggest that the novel strongest inhibitor 2-BrHA could be potentially exploited
      to control the rhamnolipid-associated group behaviors of this pathogen as well as
      for its utilization as a lead compound in screening for antimicrobial agents
      based on new antimicrobial targets. 

PMID- 24023922
TI  - How often are major blood-borne pathogens found in eye patients? A serosurvey at
      an eye hospital in Southern China.
AB  - BACKGROUND: The hepatitis B virus (HBV), hepatitis C virus (HCV), human
      immunodeficiency virus (HIV) and treponema pallidum (TP) are blood-borne
      pathogens. They can lead to nosocomial and occupational infections in health care
      settings. We aimed to identify the prevalence of and risk factors associated with
      HBV, HCV, HIV and TP infections among patients with eye diseases at a tertiary
      eye hospital in Southern China. METHODS: From July 2011 to June 2012, a total of
      26,386 blood units were collected from eye patients, including inpatients and the
      day surgery patients at Zhongshan Ophthalmic Center, one of the biggest eye
      hospitals in China. Based on the primary diagnoses from this period, the subjects
      were classified into different ocular disease groups. All blood samples were
      tested for HBsAg, anti-HCV, anti-HIV and anti-TP. RESULT: The overall prevalence
      of HBV, HCV, TP and HIV was 9.79%, 0.99%, 2.43% and 0.11%, respectively. The
      prevalence of HBsAg was much lower among patients younger than 20 years compared
      to other age groups. In addition, the risk of HBsAg was associated with the male
      gender, ocular trauma and glaucoma. The prevalence of TP increased with age and
      the prevalence among patients older than 30 was higher than that in patients
      younger than 20 years. CONCLUSIONS: The prevalence of HBV, HCV, HIV and TP in
      patients with eye diseases was identified. This information can be utilised to
      strengthen the health education and implementation of universal safety
      precautions to prevent the spread of blood-borne pathogens in health care
      settings.

PMID- 24023923
TI  - Protein structural model selection by combining consensus and single scoring
      methods.
AB  - Quality assessment (QA) for predicted protein structural models is an important
      and challenging research problem in protein structure prediction. Consensus
      Global Distance Test (CGDT) methods assess each decoy (predicted structural
      model) based on its structural similarity to all others in a decoy set and has
      been proved to work well when good decoys are in a majority cluster. Scoring
      functions evaluate each single decoy based on its structural properties. Both
      methods have their merits and limitations. In this paper, we present a novel
      method called PWCom, which consists of two neural networks sequentially to
      combine CGDT and single model scoring methods such as RW, DDFire and OPUS-Ca.
      Specifically, for every pair of decoys, the difference of the corresponding
      feature vectors is input to the first neural network which enables one to predict
      whether the decoy-pair are significantly different in terms of their GDT scores
      to the native. If yes, the second neural network is used to decide which one of
      the two is closer to the native structure. The quality score for each decoy in
      the pool is based on the number of winning times during the pairwise comparisons.
      Test results on three benchmark datasets from different model generation methods
      showed that PWCom significantly improves over consensus GDT and single scoring
      methods. The QA server (MUFOLD-Server) applying this method in CASP 10 QA
      category was ranked the second place in terms of Pearson and Spearman correlation
      performance. 

PMID- 24023924
TI  - Distal effect of amino acid substitutions in CYP2C9 polymorphic variants causes
      differences in interatomic interactions against (S)-warfarin.
AB  - Cytochrome P450 2C9 (CYP2C9) is crucial in excretion of commonly prescribed
      drugs. However, changes in metabolic activity caused by CYP2C9 polymorphisms
      inevitably result in adverse drug effects. CYP2C9*2 and *3 are prevalent in
      Caucasian populations whereas CYP2C9*13 is remarkable in Asian populations.
      Single amino acid substitutions caused by these mutations are located outside
      catalytic cavity but affect kinetic activities of mutants compared to wild-type
      enzyme. To relate distal effects of these mutations and defective drug
      metabolisms, simulations of CYP2C9 binding to anti-coagulant (S)-warfarin were
      performed as a system model. Representative (S)-warfarin-bound forms of wild-type
      and mutants were sorted and assessed through knowledge-based scoring function.
      Interatomic interactions towards (S)-warfarin were predicted to be less favorable
      in mutant structures in correlation with larger distance between hydroxylation
      site of (S)-warfarin and reactive oxyferryl heme than wild-type structure. Using
      computational approach could delineate complication of CYP polymorphism in
      management of drug therapy. 

PMID- 24023925
TI  - The significance of shifts in precipitation patterns: modelling the impacts of
      climate change and glacier retreat on extreme flood events in Denali National
      Park, Alaska.
AB  - In glacier-fed systems climate change may have various effects over a range of
      time scales, including increasing river discharge, flood frequency and magnitude.
      This study uses a combination of empirical monitoring and modelling to project
      the impacts of climate change on the glacial-fed Middle Fork Toklat River, Denali
      National Park, Alaska. We use a regional calibration of the model HBV to account
      for a paucity of long term observed flow data, validating a local application
      using glacial mass balance data and summer flow records. Two Global Climate
      Models (HADCM3 and CGCM2) and two IPCC scenarios (A2 and B2) are used to
      ascertain potential changes in meteorological conditions, river discharge, flood
      frequency and flood magnitude. Using remote sensing methods this study refines
      existing estimates of glacial recession rates, finding that since 2000, rates
      have increased from 24 m per year to 68.5m per year, with associated increases in
      ablation zone ice loss. GCM projections indicate that over the 21(st) century
      these rates will increase still further, most extensively under the CGCM2 model,
      and A2 scenarios. Due to greater winter precipitation and ice and snow
      accumulation, glaciers release increasing meltwater quantities throughout the
      21(st) century. Despite increases in glacial melt, results indicate that it is
      predominantly precipitation that affects river discharge. Three of the four IPCC
      scenarios project increases in flood frequency and magnitude, events which were
      primarily associated with changing precipitation patterns, rather than extreme
      temperature increases or meltwater release. Results suggest that although
      increasing temperatures will significantly increase glacial melt and winter
      baseflow, meltwater alone does not pose a significant flood hazard to the Toklat
      River catchment. Projected changes in precipitation are the primary concern, both
      through changing snow volumes available for melt, and more directly through
      increasing catchment runoff.

PMID- 24023926
TI  - Crabs mediate interactions between native and invasive salt marsh plants: a
      mesocosm study.
AB  - Soil disturbance has been widely recognized as an important factor influencing
      the structure and dynamics of plant communities. Although soil reworkers were
      shown to increase habitat complexity and raise the risk of plant invasion, their
      role in regulating the interactions between native and invasive species remains
      unclear. We proposed that crab activities, via improving soil nitrogen
      availability, may indirectly affect the interactions between invasive Spartina
      alterniflora and native Phragmites australis and Scirpus mariqueter in salt marsh
      ecosystems. We conducted a two-year mesocosm experiment consisting of five
      species combinations, i.e., monocultures of three species and pair-wise mixtures
      of invasive and native species, with crabs being either present or absent for
      each combination. We found that crabs could mitigate soil nitrogen depletion in
      the mesocosm over the two years. Plant performance of all species, at both the
      ramet-level (height and biomass per ramet) and plot-level (density, total above-
      and belowground biomass), were promoted by crab activities. These plants
      responded to crab disturbance primarily by clonal propagation, as plot-level
      performance was more sensitive to crabs than ramet-level. Moreover, crab
      activities altered the competition between Spartina and native plants in favor of
      the former, since Spartina was more promoted than native plants by crab
      activities. Our results suggested that crab activities may increase the
      competition ability of Spartina over native Phragmites and Scirpus through
      alleviating soil nitrogen limitation. 

PMID- 24023927
TI  - Skin lesions in European hibernating bats associated with Geomyces destructans,
      the etiologic agent of white-nose syndrome.
AB  - White-nose syndrome (WNS) has claimed the lives of millions of hibernating
      insectivorous bats in North America. Its etiologic agent, the psychrophilic
      fungus Geomyces destructans, causes skin lesions that are the hallmark of the
      disease. The fungal infection is characterized by a white powdery growth on
      muzzle, ears and wing membranes. While WNS may threaten some species of North
      American bats with regional extinction, infection in hibernating bats in Europe
      seems not to be associated with significant mortality. We performed
      histopathological investigations on biopsy samples of 11 hibernating European
      bats, originating from 4 different countries, colonized by G. destructans. One
      additional bat was euthanized to allow thorough examination of multiple strips of
      its wing membranes. Molecular analyses of touch imprints, swabs and skin samples
      confirmed that fungal structures were G. destructans. Additionally, archived
      field notes on hibernacula monitoring data in the Harz Mountains, Germany, over
      an 11-year period (2000-2011) revealed multiple capture-recapture events of 8
      banded bats repeatedly displaying characteristic fungal colonization. Skin
      lesions of G. destructans-affected hibernating European bats are intriguingly
      similar to the epidermal lesions described in North American bats. Nevertheless,
      deep invasion of fungal hyphae into the dermal connective tissue with resulting
      ulceration like in North American bats was not observed in the biopsy samples of
      European bats; all lesions found were restricted to the layers of the epidermis
      and its adnexae. Two bats had mild epidermal cupping erosions as described for
      North American bats. The possible mechanisms for any difference in outcomes of G.
      destructans infection in European and North American bats still need to be
      elucidated. 

PMID- 24023928
TI  - Juvenile king scallop, Pecten maximus, is potentially tolerant to low levels of
      ocean acidification when food is unrestricted.
AB  - The decline in ocean water pH and changes in carbonate saturation states through
      anthropogenically mediated increases in atmospheric CO2 levels may pose a hazard
      to marine organisms. This may be particularly acute for those species reliant on
      calcareous structures like shells and exoskeletons. This is of particular concern
      in the case of valuable commercially exploited species such as the king scallop,
      Pecten maximus. In this study we investigated the effects on oxygen consumption,
      clearance rates and cellular turnover in juvenile P. maximus following 3 months
      laboratory exposure to four pCO2 treatments (290, 380, 750 and 1140 uatm). None
      of the exposure levels were found to have significant effect on the clearance
      rates, respiration rates, condition index or cellular turnover (RNA: DNA) of
      individuals. While it is clear that some life stages of marine bivalves appear
      susceptible to future levels of ocean acidification, particularly under food
      limiting conditions, the results from this study suggest that where food is in
      abundance, bivalves like juvenile P. maximus may display a tolerance to limited
      changes in seawater chemistry. 

PMID- 24023929
TI  - How much can diptera-borne viruses persist over unfavourable seasons?
AB  - Diptera are vectors of major human and animal pathogens worldwide, such as
      dengue, West-Nile or bluetongue viruses. In seasonal environments, vector-borne
      disease occurrence varies with the seasonal variations of vector abundance. We
      aimed at understanding how diptera-borne viruses can persist for years under
      seasonal climates while vectors overwinter, which should stop pathogen
      transmission during winter. Modeling is a relevant integrative approach for
      investigating the large panel of persistence mechanisms evidenced through
      experimental and observational studies on specific biological systems. Inter
      seasonal persistence of virus may occur in hosts due to viremia duration, chronic
      infection, or vertical transmission, in vector resistance stages, and due to a
      low continuous transmission in winter. Using a generic stochastic modeling
      framework, we determine the parameter ranges under which virus persistence could
      occur via these different mechanisms. The parameter ranges vary according to the
      host demographic regime: for a high host population turnover, persistence
      increases with the mechanism parameter, whereas for a low turnover, persistence
      is maximal for an optimal range of parameter. Persistence in hosts due to long
      viremia duration in a few hosts or due to vertical transmission is an effective
      strategy for the virus to overwinter. Unexpectedly, a low continuous transmission
      during winter does not give rise to certain persistence, persistence barely
      occurring for a low turnover of the susceptible population. We propose a generic
      framework adaptable to most diptera-borne diseases. This framework allows ones to
      assess the plausibility of each persistence mechanism in real epidemiological
      situations and to compare the range of parameter values theoretically allowing
      persistence with the range of values determined experimentally. 

PMID- 24023930
TI  - Chinese tallow trees (Triadica sebifera) from the invasive range outperform those
      from the native range with an active soil community or phosphorus fertilization.
AB  - Two mechanisms that have been proposed to explain success of invasive plants are
      unusual biotic interactions, such as enemy release or enhanced mutualisms, and
      increased resource availability. However, while these mechanisms are usually
      considered separately, both may be involved in successful invasions. Biotic
      interactions may be positive or negative and may interact with nutritional
      resources in determining invasion success. In addition, the effects of different
      nutrients on invasions may vary. Finally, genetic variation in traits between
      populations located in introduced versus native ranges may be important for
      biotic interactions and/or resource use. Here, we investigated the roles of soil
      biota, resource availability, and plant genetic variation using seedlings of
      Triadica sebifera in an experiment in the native range (China). We manipulated
      nitrogen (control or 4 g/m(2)), phosphorus (control or 0.5 g/m(2)), soil biota
      (untreated or sterilized field soil), and plant origin (4 populations from the
      invasive range, 4 populations from the native range) in a full factorial
      experiment. Phosphorus addition increased root, stem, and leaf masses. Leaf mass
      and height growth depended on population origin and soil sterilization. Invasive
      populations had higher leaf mass and growth rates than native populations did in
      fresh soil but they had lower, comparable leaf mass and growth rates in
      sterilized soil. Invasive populations had higher growth rates with phosphorus
      addition but native ones did not. Soil sterilization decreased specific leaf area
      in both native and exotic populations. Negative effects of soil sterilization
      suggest that soil pathogens may not be as important as soil mutualists for T.
      sebifera performance. Moreover, interactive effects of sterilization and origin
      suggest that invasive T. sebifera may have evolved more beneficial relationships
      with the soil biota. Overall, seedlings from the invasive range outperformed
      those from the native range, however, an absence of soil biota or low phosphorus
      removed this advantage. 

PMID- 24023931
TI  - Reliability and validity of the CogState battery Chinese language version in
      schizophrenia.
AB  - BACKGROUND: Cognitive impairment in patients with schizophrenia is a core symptom
      of this disease. The computerized CogState Battery (CSB) has been used to detect
      seven of the most common cognitive domains in schizophrenia. The aim of this
      study was to examine the reliability and validity of the Chinese version of the
      CSB (CSB-C), in Chinese patients with schizophrenia. METHODOLOGY/PRINCIPAL
      FINDINGS: Sixty Chinese patients with schizophrenia and 58 age, sex, and
      education matched healthy controls were enrolled. All subjects completed the CSB
      C and the Repeated Battery for the Assessment of Neuropsychological Status
      (RBANS). To examine the test-retest reliability of CSB-C, we tested 33 healthy
      controls twice, at a one month interval. The Cronbach alpha value of CSB-C in
      patients was 0.81. The test-retest correlation coefficients of the Two Back Task,
      Gronton Maze Learning Task, Social Emotional Cognition Task, and Continuous
      Paired Association Learning Task were between 0.39 and 0.62 (p<0.01) in healthy
      controls. The composite scores and all subscores for the CSB-C in patients were
      significantly (p<0.01) lower than those of healthy controls. Furthermore,
      composite scores for patients on the RBANS were also significantly lower than
      those of healthy controls. Interestingly, there was a positive correlation (r =
      0.544, p<0.001) between the composite scores on CSB-C and RBANS for patients.
      Additionally, in the attention and memory cognitive domains, corresponding
      subsets from the two batteries correlated significantly (p<0.05). Moreover,
      factor analysis showed a two-factor model, consisting of speed, memory and
      reasoning. CONCLUSIONS/SIGNIFICANCE: The CSB-C shows good reliability and
      validity in measuring the broad cognitive domains of schizophrenia in affected
      Chinese patients. Therefore, the CSB-C can be used as a cognitive battery, to
      assess the therapeutic effects of potential cognitive-enhancing agents in this
      cohort.

PMID- 24023932
TI  - Potential health impacts of heavy metals on HIV-infected population in USA.
AB  - PURPOSE: Noninfectious comorbidities such as cardiovascular diseases have become
      increasingly prevalent and occur earlier in life in persons with HIV infection.
      Despite the emerging body of literature linking environmental exposures to
      chronic disease outcomes in the general population, the impacts of environmental
      exposures have received little attention in HIV-infected population. The aim of
      this study is to investigate whether individuals living with HIV have elevated
      prevalence of heavy metals compared to non-HIV infected individuals in United
      States. METHODS: We used the National Health and Nutrition Examination Survey
      (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead,
      and total mercury in HIV infected and non-HIV infected subjects. RESULTS: In this
      cross-sectional study, we found that HIV-infected individuals had higher
      concentrations of all heavy metals than the non-HIV infected group. In a
      multivariate linear regression model, HIV status was significantly associated
      with increased blood cadmium (p=0.03) after adjusting for age, sex, race,
      education, poverty income ratio, and smoking. However, HIV status was not
      statistically associated with lead or mercury levels after adjusting for the same
      covariates. CONCLUSIONS: Our findings suggest that HIV-infected patients might be
      significantly more exposed to cadmium compared to non-HIV infected individuals
      which could contribute to higher prevalence of chronic diseases among HIV
      infected subjects. Further research is warranted to identify sources of exposure
      and to understand more about specific health outcomes.

PMID- 24023933
TI  - Hydronephrotic urine in the obstructed kidney promotes urothelial carcinoma cell
      proliferation, migration, invasion through the activation of mTORC2-AKT and ERK
      signaling pathways.
AB  - Obstructive nephropathy is the most common presentation of urothelial carcinoma.
      The role of the urine in the obstructed kidney namely "hydronephrotic urine" in
      urothelial carcinoma has not been extensively explored. This study aims to
      evaluate whether hydronephrotic urine in the obstructed kidney could promote
      urothelial carcinoma. The hydronephrotic urine was collected from the obstructed
      kidneys of Sprague-Dawley rats induced by different periods of unilateral
      ureteral obstruction (UUO). By the inhibition of LY294002 and PD184352, we
      confirm that hydronephrotic urine promotes urothelial carcinoma cell (T24) and
      immortalized normal urothelial cells (E6) proliferation, migration and invasion
      in a dose-dependent manner through the activation of the mTORC2-AKT and ERK
      signaling pathways. Hydronephrotic urine also increases the expression of cyclin
      D2, cyclin-B and CDK2. It also decreases the expression of p27 and p21 in both
      urothelial carcinoma cells and normal urothelial cells. By the protein array
      study, we demonstrate that many growth factors which promote tumor cell survival
      and metastasis are over-expressed in a time-dependent manner in the
      hydronephrotic urine, including beta-FGF, IFN-gamma, PDGF-BB, PIGF, TGF-beta,
      VEGF-A, VEGF-D and EGF. These results suggest that hydronephrotic urine promotes
      normal and malignant urothelial cells proliferation, migration and invasion,
      through the activation of the mTORC2-AKT and ERK signaling pathways. Further
      investigation using live animal models of tumor growth may be needed to clarify
      aspects of these statements. 

PMID- 24023934
TI  - Hot spots in a network of functional sites.
AB  - It is of significant interest to understand how proteins interact, which holds
      the key phenomenon in biological functions. Using dynamic fluctuations in high
      frequency modes, we show that the Gaussian Network Model (GNM) predicts hot spot
      residues with success rates ranging between S 8-58%, C 84-95%, P 5-19% and A 81
      92% on unbound structures and S 8-51%, C 97-99%, P 14-50%, A 94-97% on complex
      structures for sensitivity, specificity, precision and accuracy, respectively.
      High specificity and accuracy rates with a single property on unbound protein
      structures suggest that hot spots are predefined in the dynamics of unbound
      structures and forming the binding core of interfaces, whereas the prediction of
      other functional residues with similar dynamic behavior explains the lower
      precision values. The latter is demonstrated with the case studies; ubiquitin,
      hen egg-white lysozyme and M2 proton channel. The dynamic fluctuations suggest a
      pseudo network of residues with high frequency fluctuations, which could be
      plausible for the mechanism of biological interactions and allosteric regulation.

PMID- 24023935
TI  - Small molecule suppressors of Drosophila kinesin deficiency rescue motor axon
      development in a zebrafish model of spinal muscular atrophy.
AB  - Proximal spinal muscular atrophy (SMA) is the most common inherited motor
      neuropathy and the leading hereditary cause of infant mortality. Currently there
      is no effective treatment for the disease, reflecting a need for pharmacologic
      interventions that restore performance of dysfunctional motor neurons or suppress
      the consequences of their dysfunction. In a series of assays relevant to motor
      neuron biology, we explored the activities of a collection of tetrahydroindoles
      that were reported to alter the metabolism of amyloid precursor protein (APP). In
      Drosophila larvae the compounds suppressed aberrant larval locomotion due to
      mutations in the Khc and Klc genes, which respectively encode the heavy and light
      chains of kinesin-1. A representative compound of this class also suppressed the
      appearance of axonal swellings (alternatively termed axonal spheroids or neuritic
      beads) in the segmental nerves of the kinesin-deficient Drosophila larvae. Given
      the importance of kinesin-dependent transport for extension and maintenance of
      axons and their growth cones, three members of the class were tested for
      neurotrophic effects on isolated rat spinal motor neurons. Each compound
      stimulated neurite outgrowth. In addition, consistent with SMA being an
      axonopathy of motor neurons, the three axonotrophic compounds rescued motor axon
      development in a zebrafish model of SMA. The results introduce a collection of
      small molecules as pharmacologic suppressors of SMA-associated phenotypes and
      nominate specific members of the collection for development as candidate SMA
      therapeutics. More generally, the results reinforce the perception of SMA as an
      axonopathy and suggest novel approaches to treating the disease. 

PMID- 24023936
TI  - Characterization of specific immune responses to different Aspergillus antigens
      during the course of invasive Aspergillosis in hematologic patients.
AB  - Several studies in mouse model of invasive aspergillosis (IA) and in healthy
      donors have shown that different Aspergillus antigens may stimulate different
      adaptive immune responses. However, the occurrence of Aspergillus-specific T
      cells have not yet been reported in patients with the disease. In patients with
      IA, we have investigated during the infection: a) whether and how specific T-cell
      responses to different Aspergillus antigens occur and develop; b) which antigens
      elicit the highest frequencies of protective immune responses and, c) whether
      such protective T cells could be expanded ex-vivo. Forty hematologic patients
      have been studied, including 22 patients with IA and 18 controls. Specific T
      cells producing IL-10, IFN-gamma, IL-4 and IL-17A have been characterized through
      enzyme linked immunospot and cytokine secretion assays on 88 peripheral blood
      (PB) samples, by using the following recombinant antigens: GEL1p, CRF1p, PEP1p,
      SOD1p, alpha1-3glucan, beta1-3glucan, galactomannan. Specific T cells were
      expanded through short term culture. Aspergillus-specific T cells producing non
      protective interleukin-10 (IL-10) and protective interferon-gamma (IFN-gamma)
      have been detected to all the antigens only in IA patients. Lower numbers of
      specific T cells producing IL-4 and IL-17A have also been shown. Protective T
      cells targeted predominantly Aspergillus cell wall antigens, tended to increase
      during the IA course and to be associated with a better clinical outcome.
      Aspergillus-specific T cells could be successfully generated from the PB of 8 out
      of 8 patients with IA and included cytotoxic subsets able to lyse Aspergillus
      hyphae. Aspergillus specific T-cell responses contribute to the clearance of the
      pathogen in immunosuppressed patients with IA and Aspergillus cell wall antigens
      are those mainly targeted by protective immune responses. Cytotoxic specific T
      cells can be expanded from immunosuppressed patients even during the infection by
      using the above mentioned antigens. These findings may be exploited for
      immunotherapeutic purposes in patients with IA. 

PMID- 24023937
TI  - Does diabetes appear in distinct phenotypes in young people? Results of the
      diabetes mellitus incidence Cohort Registry (DiMelli).
AB  - INTRODUCTION: The diabetes mellitus Incidence Cohort Registry (DiMelli) aims to
      characterize diabetes phenotypes by immunologic, metabolic, and genetic markers.
      We classified patients into three groups according to islet autoantibody status
      and examined whether patients with multiple diabetes-associated autoantibodies,
      one autoantibody, or without autoantibodies differed with respect to clinical,
      metabolic, and genetic parameters, including an insulin sensitivity (IS) score
      based on waist, HbA1c, and triglycerides. We also assessed whether metabolic
      markers predicted the immune status. MATERIALS AND METHODS: As of June 2012, 630
      patients in Bavaria, Germany, aged <20 years diagnosed with any type of diabetes
      within the preceding 6 months were registered in DiMelli. We compared the
      clinical and laboratory parameters between islet autoantibody status defined
      patient groups. Parameters showing the strongest associations were included in
      principal component analysis. Receiver operating characteristic curves were used
      to assess the ability of the IS Score to predict islet autoantibody status.
      RESULTS: Patients with multiple islet autoantibodies, one autoantibody, or
      without autoantibodies were significantly different in terms of BMI percentile,
      weight loss before diagnosis, fasting C-peptide (all, P<0.001), and IS Score
      (P=0.034). However, principal component analysis revealed no distinct patterns
      according to autoantibody status. At the optimal IS Score cut-off for predicting
      islet autoantibody positivity (single compared to none), the specificity was
      52.0% and the sensitivity was 86.8%. With respect to prediction of multiple
      autoantibodies (compared to none), specificity and sensitivity were slightly
      lower and in combination inferior to those obtained using the BMI percentile and
      fasting C-peptide. DISCUSSION: The DiMelli study indicated that patients with and
      without islet autoantibodies differed with respect to metabolic and genetic
      markers but there was considerable overlap of phenotypes, and autoantibody status
      could not be predicted by these parameters. Thus, our results suggest that
      refined diabetes classification may require both immune and metabolic
      phenotyping.

PMID- 24023938
TI  - CK2 inhibitor CX-4945 blocks TGF-beta1-induced epithelial-to-mesenchymal
      transition in A549 human lung adenocarcinoma cells.
AB  - BACKGROUND: The epithelial-to-mesenchymal transition (EMT) is a major phenotype
      of cancer metastasis and invasion. As a druggable cancer target, the inhibition
      of protein kinase CK2 (formally named to casein kinase 2) has been suggested as a
      promising therapeutic strategy to treat EMT-controlled cancer metastasis. This
      study aimed to evaluate the effect of the CK2 inhibitor CX-4945 on the processes
      of cancer migration and invasion during the EMT in A549 human lung adenocarcinoma
      cells. MATERIALS AND METHODS: The effect of CX-4945 on TGF-beta1-induced EMT was
      evaluated in A549 cells treated with TGF-beta1 (5 ng/ml) and CX-4945. The effect
      of CX-4945 on TGF-beta1-induced cadherin switch and activation of key signaling
      molecules involved in Smad, non-Smad, Wnt and focal adhesion signaling pathways
      were investigated by Western blot analysis, immunocytochemistry and reporter
      assay. Additionally, the effect of CX-4945 on TGF-beta1-induced migration and
      invasion was investigated by wound healing assay, Boyden chamber assay, gelatin
      zymography, and the quantitative real-time PCR. RESULTS: CX-4945 inhibits the TGF
      beta1-induced cadherin switch and the activation of key signaling molecules
      involved in Smad (Smad2/3, Twist and Snail), non-Smad (Akt and Erk), Wnt (beta
      catenin) and focal adhesion signaling pathways (FAK, Src and paxillin) that
      cooperatively regulate the overall process of EMT. As a result, CX-4945 inhibits
      the migration and invasion of A549 cells accompanied with the downregulation of
      MMP-2 and 9. CONCLUSIONS: Clinical evaluation of CX-4945 in humans as a single
      agent in solid tumors and multiple myeloma has established its promising
      pharmacokinetic, pharmacodynamic, and safety profiles. Beyond regression of tumor
      mass, CX-4945 may be advanced as a new therapy for cancer metastasis and EMT
      related disorders.

PMID- 24023939
TI  - Pseudomonas aeruginosa exotoxin Y-mediated tau hyperphosphorylation impairs
      microtubule assembly in pulmonary microvascular endothelial cells.
AB  - Pseudomonas aeruginosa uses a type III secretion system to introduce the adenylyl
      and guanylyl cyclase exotoxin Y (ExoY) into the cytoplasm of endothelial cells.
      ExoY induces Tau hyperphosphorylation and insolubility, microtubule breakdown,
      barrier disruption and edema, although the mechanism(s) responsible for
      microtubule breakdown remain poorly understood. Here we investigated both
      microtubule behavior and centrosome activity to test the hypothesis that ExoY
      disrupts microtubule dynamics. Fluorescence microscopy determined that infected
      pulmonary microvascular endothelial cells contained fewer microtubules than
      control cells, and further studies demonstrated that the microtubule-associated
      protein Tau was hyperphosphorylated following infection and dissociated from
      microtubules. Disassembly/reassembly studies determined that microtubule assembly
      was disrupted in infected cells, with no detectable effects on either microtubule
      disassembly or microtubule nucleation by centrosomes. This effect of ExoY on
      microtubules was abolished when the cAMP-dependent kinase phosphorylation site
      (Ser-214) on Tau was mutated to a non-phosphorylatable form. These studies
      identify Tau in microvascular endothelial cells as the target of ExoY in control
      of microtubule architecture following pulmonary infection by Pseudomonas
      aeruginosa and demonstrate that phosphorylation of tau following infection
      decreases microtubule assembly. 

PMID- 24023940
TI  - Elevated functional connectivity in a striatal-amygdala circuit in pathological
      gamblers.
AB  - Both substance-based addiction and behavioural impulse control disorders (ICDs)
      have been associated with dysfunctions of the ventral striatum. Recent studies
      using functional connectivity techniques have revealed increased coupling of the
      ventral striatum with other limbic regions such as amygdala and orbitofrontal
      cortex in patients with substance abuse disorders and attention-deficit
      hyperactivity disorder. In the present study, we re-analyzed previously published
      functional magnetic resonance imaging data acquired in pathological gamblers and
      controls during value-based decision-making to investigate whether PG is
      associated with similar functional connectivity effects. In line with previous
      studies in other ICDs, we observed reliable increases in functional coupling
      between striatum and bilateral amygdala in gamblers vs. controls. Implications of
      these findings for neural models of self-control and addiction are discussed. 

PMID- 24023941
TI  - A critical role for proinflammatory behavior of smooth muscle cells in
      hemodynamic initiation of intracranial aneurysm.
AB  - BACKGROUND: Intracranial aneurysm initiation is poorly understood, although
      hemodynamic insult is believed to play an important role in triggering the
      pathology. It has recently been found in a rabbit model that while macrophages
      are absent during hemodynamic aneurysm initiation, matrix metalloproteinases
      (MMPs) are elevated and co-localize with smooth muscle cells (SMCs). This study
      investigates whether SMCs play a mechanistic role in aneurysm initiation
      triggered by hemodynamics. METHODS: Aneurysmal damage was induced at the basilar
      terminus via bilateral common carotid artery ligation in rabbits (n = 45, plus 7
      sham controls). 16 ligated rabbits were treated with doxycycline to inhibit MMPs,
      7 received clodronate liposomes to deplete circulating monocytes, and the rest
      received no drug. Effects of the treatments on aneurysm development were assessed
      histologically 5 days and 6 months after ligation. MMP production and expression
      of inflammatory markers by SMCs was monitored by immunohistochemistry and in situ
      hybridization. RESULTS: Treatment with doxycycline attenuated aneurysmal
      development examined at 5 days and 6 months, suggesting that MMPs contribute to
      aneurysm initiation. However, systemic depletion of macrophages did not decrease
      MMPs or suppress aneurysmal development. Immunofluorescence showed that during
      aneurysm initiation MMP-2 and MMP-9 were distributed in SMCs, and in situ
      hybridization indicated that they were transcribed by SMCs. In regions of early
      aneurysmal lesion, SMCs exhibited decreased expression of smooth muscle actin and
      increased NF-kappaB and MCP-1 expressions. CONCLUSIONS: During aneurysm
      initiation triggered by hemodynamics, SMCs rather than macrophages are
      responsible for MMP production that is critical for aneurysmal lesion
      development. These SMCs exhibit proinflammatory behavior.

PMID- 24023942
TI  - Skill set or mind set? Associations between health literacy, patient activation
      and health.
AB  - OBJECTIVE: There is ongoing debate on whether health literacy represents a skill
      based construct for health self-management, or if it also more broadly captures
      personal 'activation' or motivation to manage health. This research examines 1)
      the association between patient activation and health literacy as they are most
      commonly measured and 2) the independent and combined associations of patient
      activation and health literacy skills with physical and mental health. METHODS: A
      secondary analysis of baseline cross-sectional data from the LitCog cohort of
      older adults was used. Participants (n = 697) were recruited from multiple US
      based health centers. During structured face-to-face interviews, participants
      completed the Test of Functional Health Literacy in Adults (TOFHLA), the Patient
      Activation Measure (PAM), the SF-36 physical health summary subscale, and Patient
      Reported Outcomes Measurement Information Service (PROMIS) short form subscales
      for depression and anxiety. RESULTS: The relationship between health literacy and
      patient activation was weak, but significant (r = 0.11, p<0.01). In models
      adjusted for participant characteristics, lower health literacy was associated
      with worse physical health (beta = 0.13, p<0.001) and depression (beta = -0.16,
      p<0.001). Lower patient activation was associated with worse physical health
      (beta = 0.19, p<0.001), depression (beta = -0.27, p<0.001) and anxiety (beta
      0.24, p<0.001). CONCLUSIONS: The most common measures of health literacy and
      patient activation are weakly correlated with each other, but also independently
      correlated with health outcomes. This suggests health literacy represents a
      distinct skill-based construct, supporting the Institute of Medicine's
      definition. Deficits in either construct could be useful targets for behavioral
      intervention.

PMID- 24023943
TI  - The effect of pstS and phoB on quorum sensing and swarming motility in
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that can cause a wide range
      of infections and inflammations in a variety of hosts, such as chronic biofilm
      associated lung infections in Cystic Fibrosis patients. Phosphate, an essential
      nutrient, has been recognized as an important signal that affects virulence in P.
      aeruginosa. In the current study we examined the connection between phosphate
      regulation and surface motility in P. aeruginosa. We focused on two important
      genes, pstS, which is involved in phosphate uptake, and phoB, a central regulator
      that responds to phosphate starvation. We found that a mutant lacking pstS is
      constantly starved for phosphate and has a hyper swarming phenotype. Phosphate
      starvation also induced swarming in the wild type. The phoB mutant, on the other
      hand, did not express phosphate starvation even when phosphate was limited and
      showed no swarming. A double mutant lacking both genes (pstS and phoB) showed a
      similar phenotype to the phoB mutant (i.e. no swarming). This highlights the role
      of phoB in controlling swarming motility under phosphate-depleted conditions.
      Finally, we were able to demonstrate that PhoB controls swarming by up-regulating
      the Rhl quorum sensing system in P. aeruginosa, which resulted in hyper
      production of rhamonlipids: biosurfactants that are known to induce swarming
      motility. 

PMID- 24023944
TI  - Predicting free-space occupancy on novel artificial structures by an invasive
      intertidal barnacle using a removal experiment.
AB  - Artificial structures can create novel habitat in the marine environment that has
      been associated with the spread of invasive species. They are often located in
      areas of high disturbance and can vary significantly in the area of free space
      provided for settlement of marine organisms. Whilst correlation between the
      amount of free space available and recruitment success has been shown in
      populations of several marine benthic organisms, there has been relatively little
      focus on invasive species, a group with the potential to reproduce in vast
      numbers and colonise habitats rapidly. Invasion success following different
      scales of disturbance was examined in the invasive acorn barnacle,
      Austrominiusmodestus, on a unique art installation located in Liverpool Bay.
      Population growth and recruitment success were examined by comparing recruitment
      rates within disturbance clearings of 4 different sizes and by contrasting
      population development with early recruitment rates over a 10 week period.
      Disturbed areas were rapidly recolonised and monocultures of A. modestus formed
      within 6 weeks. The size of patch created during disturbance had no effect on the
      rate of recruitment, while a linear relationship between recruit density and
      patch size was observed. Density-dependent processes mediated initial high
      recruitment resulting in population stability after 8-10 weeks, but densities
      continued to greatly exceed those reported in natural habitats. Given that
      artificial structures are likely to continue to proliferate in light of climate
      change projections, free-space is likely to become more available more frequently
      in the future supporting the expansion of fast-colonising species. 

PMID- 24023945
TI  - The HIV-1 Nef protein binds argonaute-2 and functions as a viral suppressor of
      RNA interference.
AB  - The HIV-1 accessory protein Nef is an important virulence factor. It associates
      with cellular membranes and modulates the endocytic machinery and signaling
      pathways. Nef also increases the proliferation of multivesicular bodies (MVBs),
      which are sites for virus assembly and budding in macrophages. The RNA
      interference (RNAi) pathway proteins Ago2 and GW182 localize to MVBs, suggesting
      these to be sites for assembly and turnover of the miRNA-induced silencing
      complex (miRISC). While RNAi affects HIV replication, it is not clear if the
      virus encodes a suppressor activity to overcome this innate host response. Here
      we show that Nef colocalizes with MVBs and binds Ago2 through two highly
      conserved Glycine-Tryptophan (GW) motifs, mutations in which abolish Nef binding
      to Ago2 and reduce virus yield and infectivity. Nef also inhibits the slicing
      activity of Ago2 and disturbs the sorting of GW182 into exosomes resulting in the
      suppression of miRNA-induced silencing. Thus, besides its other activities, the
      HIV-1 Nef protein is also proposed to function as a viral suppressor of RNAi
      (VSR). 

PMID- 24023946
TI  - A common construction pattern of English words and Chinese characters.
AB  - Rankings are ubiquitous around the world. Here I investigate spatial ranking
      patterns of English Words and Chinese Characters, and reveal a common
      construction pattern related to phase separation. In detail, I analyze a list of
      different words in the English language, and find that the frequency of the
      number of letters per word linearly or nonlinearly decays over its rank in the
      frequency table. I interpret the linearly decaying area as a linear phase that
      covers 96.4% words, which is in sharp contrast to a nonlinear phase (representing
      the nonlinearly decaying area) that covers the remaining 3.6% words. Amazingly,
      the phase separation phenomenon with the same two percentages of 96.4% and 3.6%
      holds also for the relation between strokes and characters in the Chinese
      language although English and Chinese are two distinctly different language
      systems. The common construction pattern originates from the log-normal
      distributions of frequencies of words or characters, which can be understood by
      the joint effect of both the Weber-Fechner law in psychophysics and the principle
      of maximum entropy in information theory. 

PMID- 24023947
TI  - Methylenetetrahydrofolate reductase gene polymorphism and risk of type 2 diabetes
      mellitus.
AB  - OBJECTIVE: This review aimed to comprehensively assess the literature examining a
      possible link between the rs1801133 polymorphism (677C -> T) in the gene encoding
      the methylenetetrahydrofolate reductase (MTHFR) gene and risk of type 2 diabetes
      mellitus (DM). RESEARCH DESIGN AND METHODS: Several research databases were
      systematically searched for studies examining the genotype at the rs1801133
      polymorphism in healthy control individuals and individuals with type 2 DM.
      Genotype frequency data were examined across all studies and across subsets of
      studies according to ethnicity and presence of serious DM-related complications.
      Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: A
      total of 4855 individuals with type 2 DM and 5242 healthy controls from 15
      countries comprising Asian, Caucasian and African ethnicities were found to
      satisfy the inclusion criteria and included in the review. Genotype at the
      rs1801133 polymorphism was not consistently associated with either increased or
      reduced risk of type 2 DM; the OR across all studies was 0.91 (95%CI 0.82 to
      1.00) for the C- vs. T-allele, 0.88 (0.75 to 1.03) for CC vs. CT+TT, 0.82 (0.71
      to 0.95) for CC vs. TT, and 1.15 (1.03 to 1.29) for TT vs. CC+CT. Similar results
      were found when the meta-analysis was repeated separately for each ethnic
      subgroup, and for subgroups with or without serious DM-related complications.
      CONCLUSIONS: There does not appear to be compelling evidence of an association
      between the genotype at the rs1801133 polymorphism of the MTHFR gene and risk of
      type 2 DM.

PMID- 24023948
TI  - Fibromyalgia: anti-inflammatory and stress responses after acute moderate
      exercise.
AB  - Fibromyalgia (FM) is characterized in part by an elevated inflammatory status,
      and "modified exercise" is currently proposed as being a good therapeutic help
      for these patients. However, the mechanisms involved in the exercise-induced
      benefits are still poorly understood. The objective was to evaluate the effect of
      a single bout of moderate cycling (45 min at 55% VO2 max) on the inflammatory
      (serum IL-8; chemotaxis and O2 (-) production by neutrophils; and IL-1beta, TNF
      alpha, IL-6, IL-10, and IL-18 release by monocytes) and stress (cortisol; NA; and
      eHsp72) responses in women diagnosed with FM compared with an aged-matched
      control group of healthy women (HW). IL-8, NA, and eHsp72 were determined by
      ELISA. Cytokines released by monocytes were determined by Bio-Plex(r) system
      (LUMINEX). Cortisol was determined by electrochemoluminiscence, chemotaxis was
      evaluated in Boyden chambers and O2 (-) production by NBT reduction. In the FM
      patients, the exercise induced a decrease in the systemic concentration of IL-8,
      cortisol, NA, and eHsp72; as well as in the neutrophil's chemotaxis and O2 (-)
      production and in the inflammatory cytokine release by monocytes. This was
      contrary to the completely expected exercise-induced increase in all those
      biomarkers in HW. In conclusion, single sessions of moderate cycling can improve
      the inflammatory status in FM patients, reaching values close to the situation of
      aged-matched HW at their basal status. The neuroendocrine mechanism seems to be
      an exercise-induced decrease in the stress response of these patients. 

PMID- 24023950
TI  - Social learning in the ultimatum game.
AB  - In the ultimatum game, two players divide a sum of money. The proposer suggests
      how to split and the responder can accept or reject. If the suggestion is
      rejected, both players get nothing. The rational solution is that the responder
      accepts even the smallest offer but humans prefer fair share. In this paper, we
      study the ultimatum game by a learning-mutation process based on quantal response
      equilibrium, where players are assumed boundedly rational and make mistakes when
      estimating the payoffs of strategies. Social learning is never stabilized at the
      fair outcome or the rational outcome, but leads to oscillations from offering 40
      percent to 50 percent. To be precise, there is a clear tendency to increase the
      mean offer if it is lower than 40 percent, but will decrease when it reaches the
      fair offer. If mutations occur rarely, fair behavior is favored in the limit of
      local mutation. If mutation rate is sufficiently high, fairness can evolve for
      both local mutation and global mutation. 

PMID- 24023949
TI  - Long-term cardiovascular fitness is associated with auditory attentional control
      in old adults: neuro-behavioral evidence.
AB  - It has been shown that healthy aging affects the ability to focus attention on a
      given task and to ignore distractors. Here, we asked whether long-term physical
      activity is associated with lower susceptibility to distraction of auditory
      attention, and how physically active and inactive seniors may differ regarding
      subcomponents of auditory attention. An auditory duration discrimination task was
      employed, and involuntary attentional shifts to task-irrelevant rare frequency
      deviations and subsequent reorientation were studied by analysis of behavioral
      data and event-related potential measures. The frequency deviations impaired
      performance more in physically inactive than active seniors. This was accompanied
      by a stronger frontal positivity (P3a) and increased activation of anterior
      cingulate cortex, suggesting a stronger involuntary shift of attention towards
      task-irrelevant stimulus features in inactive compared to active seniors. These
      results indicate a positive relationship between physical fitness and attentional
      control in elderly, presumably due to more focused attentional resources and
      enhanced inhibition of irrelevant stimulus features. 

PMID- 24023951
TI  - Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit
      vaccination model.
AB  - BACKGROUND: Ten to 30% of HIV-1 infected subjects develop broadly neutralizing
      antibodies (bNAbs) during chronic infection. We hypothesized that immunizing
      rabbits with viral envelope glycoproteins (Envs) from these patients may induce
      bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant.
      METHODS: Based on in vitro neutralizing activity in serum, patients with bNAbs
      were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140
      proteins were generated from sequences derived from four adults and two children
      infected with either clade A or B HIV-1. From one of the clade A Envs both the
      monomeric and trimeric Env were produced for comparison. Rabbits were immunized
      with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant
      dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01). Env binding in rabbit
      immune serum was determined using ELISAs based on gp120-IIIB protein.
      Neutralizing activity of IgG purified from rabbit immune sera was measured with
      the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected
      experiments. RESULTS: It was initially established that gp140 trimers induce
      better antibody responses over gp120 monomers and that the adjuvant CAF01 was
      necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from
      patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to
      Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with
      titers, and an gp120-binding IgG titer above a threshold of 100,000 was
      predictive of neutralization capability. Finally, peptide inhibition experiments
      showed that a large fraction of the neutralizing IgG was directed against the
      gp120 V3 region. CONCLUSIONS: Our results indicate that the strategy of reverse
      immunology based on selected Env sequences is promising when immunogens are
      delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a
      valuable model for HIV vaccine studies.

PMID- 24023952
TI  - Short-term feed deprivation alters immune status of surface mucosa in channel
      catfish (Ictalurus punctatus).
AB  - Short-term feed deprivation (or fasting) is a common occurrence in aquacultured
      fish species whether due to season, production strategies, or disease. In channel
      catfish (Ictalurus punctatus) fasting impacts susceptibility to several bacterial
      pathogens including Flavobacterium columnare, the causative agent of columnaris
      disease. As columnaris gains entry through the gills and skin of fish, we
      examined here changes in transcriptional regulation induced in these surface
      mucosal tissues due to short-term (7 day) fasting. RNA-seq expression analysis
      revealed a total of 1,545 genes perturbed by fasting. Fasting significantly
      altered expression of critical innate immune factors in a manner consistent with
      lower immune fitness as well as dysregulating key genes involved in energy
      metabolism and cell cycling/proliferation. Downregulation of innate immune actors
      such as iNOS2b, Lysozyme C, and peptidoglycan recognition protein 6 is predicted
      to impact the delicate recognition/tolerance balance for commensal and pathogenic
      bacteria on the skin and gill. The highlighted expression profiles reveal
      potential mechanistic similarities between gut and surface mucosa and underscore
      the complex interrelationships between nutrition, mucosal integrity, and immunity
      in teleost fish. 

PMID- 24023953
TI  - A low-cost EEG system-based hybrid brain-computer interface for humanoid robot
      navigation and recognition.
AB  - This paper describes a hybrid brain-computer interface (BCI) technique that
      combines the P300 potential, the steady state visually evoked potential (SSVEP),
      and event related de-synchronization (ERD) to solve a complicated multi-task
      problem consisting of humanoid robot navigation and control along with object
      recognition using a low-cost BCI system. Our approach enables subjects to control
      the navigation and exploration of a humanoid robot and recognize a desired object
      among candidates. This study aims to demonstrate the possibility of a hybrid BCI
      based on a low-cost system for a realistic and complex task. It also shows that
      the use of a simple image processing technique, combined with BCI, can further
      aid in making these complex tasks simpler. An experimental scenario is proposed
      in which a subject remotely controls a humanoid robot in a properly sized maze.
      The subject sees what the surrogate robot sees through visual feedback and can
      navigate the surrogate robot. While navigating, the robot encounters objects
      located in the maze. It then recognizes if the encountered object is of interest
      to the subject. The subject communicates with the robot through SSVEP and ERD
      based BCIs to navigate and explore with the robot, and P300-based BCI to allow
      the surrogate robot recognize their favorites. Using several evaluation metrics,
      the performances of five subjects navigating the robot were quite comparable to
      manual keyboard control. During object recognition mode, favorite objects were
      successfully selected from two to four choices. Subjects conducted humanoid
      navigation and recognition tasks as if they embodied the robot. Analysis of the
      data supports the potential usefulness of the proposed hybrid BCI system for
      extended applications. This work presents an important implication for the future
      work that a hybridization of simple BCI protocols provide extended
      controllability to carry out complicated tasks even with a low-cost system. 

PMID- 24023954
TI  - Humans process dog and human facial affect in similar ways.
AB  - Humans share aspects of their facial affect with other species such as dogs. Here
      we asked whether untrained human observers with and without dog experience are
      sensitive to these aspects and recognize dog affect with better-than-chance
      accuracy. Additionally, we explored similarities in the way observers process dog
      and human expressions. The stimulus material comprised naturalistic facial
      expressions of pet dogs and human infants obtained through positive (i.e., play)
      and negative (i.e., social isolation) provocation. Affect recognition was
      assessed explicitly in a rating task using full face images and images cropped to
      reveal the eye region only. Additionally, affect recognition was assessed
      implicitly in a lexical decision task using full faces as primes and emotional
      words and pseudowords as targets. We found that untrained human observers rated
      full face dog expressions from the positive and negative condition more
      accurately than would be expected by chance. Although dog experience was
      unnecessary for this effect, it significantly facilitated performance.
      Additionally, we observed a range of similarities between human and dog face
      processing. First, the facial expressions of both species facilitated lexical
      decisions to affectively congruous target words suggesting that their processing
      was equally automatic. Second, both dog and human negative expressions were
      recognized from both full and cropped faces. Third, female observers were more
      sensitive to affective information than were male observers and this difference
      was comparable for dog and human expressions. Together, these results extend
      existing work on cross-species similarities in facial emotions and provide
      evidence that these similarities are naturally exploited when humans interact
      with dogs. 

PMID- 24023955
TI  - Specific extracellular matrix remodeling signature of colon hepatic metastases.
AB  - To identify genes implicated in metastatic colonization of the liver in
      colorectal cancer, we collected pairs of primary tumors and hepatic metastases
      before chemotherapy in 13 patients. We compared mRNA expression in the pairs of
      patients to identify genes deregulated during metastatic evolution. We then
      validated the identified genes using data obtained by different groups. The 33
      gene signature was able to classify 87% of hepatic metastases, 98% of primary
      tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six
      datasets obtained using five different microarray platforms. The identified genes
      are specific to colon cancer and hepatic metastases since other metastatic
      locations and hepatic metastases originating from breast cancer were not
      classified by the signature. Gene Ontology term analysis showed that 50% of the
      genes are implicated in extracellular matrix remodeling, and more precisely in
      cell adhesion, extracellular matrix organization and angiogenesis. Because of the
      high efficiency of the signature to classify colon hepatic metastases, the
      identified genes represent promising targets to develop new therapies that will
      specifically affect hepatic metastasis microenvironment. 

PMID- 24023956
TI  - Vascular endothelial growth factor receptor-2 promotes the development of the
      lymphatic vasculature.
AB  - Vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed by
      lymphatic endothelial cells and has been shown to stimulate lymphangiogenesis in
      adult mice. However, the role VEGFR2 serves in the development of the lymphatic
      vascular system has not been defined. Here we use the Cre-lox system to show that
      the proper development of the lymphatic vasculature requires VEGFR2 expression by
      lymphatic endothelium. We show that Lyve-1(wt/Cre);Vegfr2(flox/flox) mice possess
      significantly fewer dermal lymphatic vessels than Vegfr2(flox/flox) mice.
      Although Lyve-1(wt/Cre);Vegfr2(flox/flox) mice exhibit lymphatic hypoplasia, the
      lymphatic network is functional and contains all of the key features of a normal
      lymphatic network (initial lymphatic vessels and valved collecting vessels
      surrounded by smooth muscle cells (SMCs)). We also show that Lyve-1(Cre) mice
      display robust Cre activity in macrophages and in blood vessels in the yolk sac,
      liver and lung. This activity dramatically impairs the development of blood
      vessels in these tissues in Lyve-1(wt/Cre);Vegfr2(flox/flox) embryos, most of
      which die after embryonic day14.5. Lastly, we show that inactivation of Vegfr2 in
      the myeloid lineage does not affect the development of the lymphatic vasculature.
      Therefore, the abnormal lymphatic phenotype of Lyve-1(wt/Cre);Vegfr2(flox/flox)
      mice is due to the deletion of Vegfr2 in the lymphatic vasculature not
      macrophages. Together, this work demonstrates that VEGFR2 directly promotes the
      expansion of the lymphatic network and further defines the molecular mechanisms
      controlling the development of the lymphatic vascular system. 

PMID- 24023957
TI  - Periodontal ligament, cementum, and alveolar bone in the oldest herbivorous
      tetrapods, and their evolutionary significance.
AB  - Tooth implantation provides important phylogenetic and functional information
      about the dentitions of amniotes. Traditionally, only mammals and crocodilians
      have been considered truly thecodont, because their tooth roots are coated in
      layers of cementum for anchorage of the periodontal ligament, which is in turn
      attached to the bone lining the alveolus, the alveolar bone. The histological
      properties and developmental origins of these three periodontal tissues have been
      studied extensively in mammals and crocodilians, but the identities of the
      periodontal tissues in other amniotes remain poorly studied. Early work on dental
      histology of basal amniotes concluded that most possess a simplified tooth
      attachment in which the tooth root is ankylosed to a pedestal composed of "bone
      of attachment", which is in turn fused to the jaw. More recent studies have
      concluded that stereotypically thecodont tissues are also present in non
      mammalian, non-crocodilian amniotes, but these studies were limited to crown
      groups or secondarily aquatic reptiles. As the sister group to Amniota, and the
      first tetrapods to exhibit dental occlusion, diadectids are the ideal candidates
      for studies of dental evolution among terrestrial vertebrates because they can be
      used to test hypotheses of development and homology in deep time. Our study of
      Permo-Carboniferous diadectid tetrapod teeth and dental tissues reveal the
      presence of two types of cementum, periodontal ligament, and alveolar bone, and
      therefore the earliest record of true thecodonty in a tetrapod. These discoveries
      in a stem amniote allow us to hypothesize that the ability to produce the tissues
      that characterize thecodonty in mammals and crocodilians is very ancient and
      plesiomorphic for Amniota. Consequently, all other forms of tooth implantation in
      crown amniotes are derived arrangements of one or more of these periodontal
      tissues and not simply ankylosis of teeth to the jaw by plesiomorphically
      retaining "bone of attachment", as previously suggested. 

PMID- 24023958
TI  - "My worries are rational, climate change is not": habitual ecological worrying is
      an adaptive response.
AB  - Qualifications such as "global warming hysteria" and "energy policy
      schizophrenia" put forward by some climate change skeptics, usually outside the
      academic arena, may suggest that people who seriously worry about the environment
      suffer from psychological imbalance. The present study aimed to refute this
      thesis. While habitual worrying in general is strongly associated with
      psychopathological symptoms, in a survey a near-zero correlation was found
      between habitual ecological worrying and pathological worry. Instead, habitual
      ecological worrying was associated with pro-environmental attitudes and
      behaviors, and with a personality structure characterized by imagination and an
      appreciation for new ideas. The study had sufficient statistical power and
      measures were valid and reliable. The results confirm that those who habitually
      worry about the ecology are not only lacking in any psychopathology, but
      demonstrate a constructive and adaptive response to a serious problem. In the
      public domain, these findings may contribute to a more rational and less
      emotional debate on climate change and to the prevention of stigmatization of
      people who are genuinely concerned about our habitat and are prepared to do
      something about it ("habitual worriers are not crazy"). In the academic arena
      this study may contribute to environmental psychology ("habitual worrying is part
      of a green identity"), as well as to the literature on worry and anxiety
      ("habitual worrying can be a constructive response"). 

PMID- 24023959
TI  - Association between sleep duration and cancer risk: a meta-analysis of
      prospective cohort studies.
AB  - BACKGROUND: Sleep duration has been shown to play an important role in the
      development of cancer. However, the results have been inconsistent. A meta
      analysis with prospective cohort studies was performed to clarify the association
      between short or long sleep duration and cancer risk. METHODS: PubMed and Embase
      databases were searched for eligible publications. Pooled relative risk (RR) with
      95% confidence interval (CI) was calculated using random- or fixed- model.
      RESULTS: A total of 10 prospective studies (8392 incident cases and 555678
      participants) were included in the meta-analysis. Neither short nor long sleep
      duration was statistically associated with increased risk of cancer (short sleep
      duration: RR=1.05, 95%CI=0.90-1.24, p=0.523; long sleep duration: RR=0.92,
      95%CI=0.76-1.12, p=0.415). In the subgroup by cancer type, long sleep duration
      was positively associated with colorectal cancer (RR=1.29, 95%CI=1.09-1.52,
      p=0.003). CONCLUSION: The present meta-analysis suggested that neither short nor
      long sleep duration was significantly associated with risk of cancer, although
      long sleep duration increased risk of with colorectal cancer. Large-scale well
      design prospective studies are required to be conducted to further investigate
      the observed association.

PMID- 24023960
TI  - The evolutionary fate of phenotypic plasticity and functional traits under
      domestication in manioc: changes in stem biomechanics and the appearance of stem
      brittleness.
AB  - Domestication can influence many functional traits in plants, from overall life
      history and growth form to wood density and cell wall ultrastructure. Such
      changes can increase fitness of the domesticate in agricultural environments but
      may negatively affect survival in the wild. We studied effects of domestication
      on stem biomechanics in manioc by comparing domesticated and ancestral wild taxa
      from two different regions of greater Amazonia. We compared mechanical
      properties, tissue organisation and wood characteristics including microfibril
      angles in both wild and domesticated plants, each growing in two different
      habitats (forest or savannah) and varying in growth form (shrub or liana). Wild
      taxa grew as shrubs in open savannah but as lianas in overgrown and forested
      habitats. Growth form plasticity was retained in domesticated manioc. However,
      stems of the domesticate showed brittle failure. Wild plants differed in
      mechanical architecture between shrub and liana phenotypes, a difference that
      diminished between shrubs and lianas of the domesticate. Stems of wild plants
      were generally stiffer, failed at higher bending stresses and were less prone to
      brittle fracture compared with shrub and liana phenotypes of the domesticate.
      Biomechanical differences between stems of wild and domesticated plants were
      mainly due to changes in wood density and cellulose microfibril angle rather than
      changes in secondary growth or tissue geometry. Domestication did not
      significantly modify "large-scale" trait development or growth form plasticity,
      since both wild and domesticated manioc can develop as shrubs or lianas. However,
      "finer-scale" developmental traits crucial to mechanical stability and thus
      ecological success of the plant were significantly modified. This profoundly
      influenced the likelihood of brittle failure, particularly in long climbing
      stems, thereby also influencing the survival of the domesticate in natural
      situations vulnerable to mechanical perturbation. We discuss the different
      selective pressures that could explain evolutionary modifications of stem
      biomechanical properties under domestication in manioc. 

PMID- 24023961
TI  - Agrobacterium mediated transient gene silencing (AMTS) in Stevia rebaudiana:
      insights into steviol glycoside biosynthesis pathway.
AB  - BACKGROUND: Steviol glycoside biosynthesis pathway has emerged as bifurcation
      from ent-kaurenoic acid, substrate of methyl erythritol phosphate pathway that
      also leads to gibberellin biosynthesis. However, the genetic regulation of
      steviol glycoside biosynthesis has not been studied. So, in present study RNA
      interference (RNAi) based Agrobacterium mediated transient gene silencing (AMTS)
      approach was followed. SrKA13H and three SrUGTs (SrUGT85C2, SrUGT74G1 and
      SrUGT76G1) genes encoding ent-kaurenoic acid-13 hydroxylase and three UDP
      glycosyltransferases of steviol glycoside biosynthesis pathway were silenced in
      Stevia rebaudiana to understand its molecular mechanism and association with
      gibberellins. METHODOLOGY/PRINCIPAL FINDINGS: RNAi mediated AMTS of SrKA13H and
      three SrUGTs has significantly reduced the expression of targeted endogenous
      genes as well as total steviol glycoside accumulation. While gibberellins (GA3)
      content was significantly enhanced on AMTS of SrUGT85C2 and SrKA13H. Silencing of
      SrKA13H and SrUGT85C2 was found to block the metabolite flux of steviol glycoside
      pathway and shifted it towards GA3 biosynthesis. Further, molecular docking of
      three SrUGT proteins has documented highest affinity of SrUGT76G1 for the
      substrates of alternate pathways synthesizing steviol glycosides. This could be a
      plausible reason for maximum reduction in steviol glycoside content on silencing
      of SrUGT76G1 than other genes. CONCLUSIONS: SrKA13H and SrUGT85C2 were identified
      as regulatory genes influencing carbon flux between steviol glycoside and
      gibberellin biosynthesis. This study has also documented the existence of
      alternate steviol glycoside biosynthesis route.

PMID- 24023962
TI  - Effects of knots on protein folding properties.
AB  - This work explores the impact of knots, knot depth and motif of the threading
      terminus in protein folding properties (kinetics, thermodynamics and mechanism)
      via extensive Monte Carlo simulations of lattice models. A knotted backbone has
      no effect on protein thermodynamic stability but it may affect key aspects of
      folding kinetics. In this regard, we found clear evidence for a functional
      advantage of knots: knots enhance kinetic stability because a knotted protein
      unfolds at a distinctively slower rate than its unknotted counterpart. However,
      an increase in knot deepness does not necessarily lead to more effective changes
      in folding properties. In this regard, a terminus with a non-trivial conformation
      (e.g. hairpin) can have a more dramatic effect in enhancing kinetic stability
      than knot depth. Nevertheless, our results suggest that the probability of the
      denatured ensemble to keep knotted is higher for proteins with deeper knots,
      indicating that knot depth plays a role in determining the topology of the
      denatured state. Refolding simulations starting from denatured knotted
      conformations show that not every knot is able to nucleate folding and further
      indicate that the formation of the knotting loop is a key event in the folding of
      knotted trefoils. They also show that there are specific native contacts within
      the knotted core that are crucial to keep a native knotting loop in denatured
      conformations which otherwise have no detectable structure. The study of the
      knotting mechanism reveals that the threading of the knotting loop generally
      occurs towards late folding in conformations that exhibit a significant degree of
      structural consolidation. 

PMID- 24023963
TI  - Detection of A. phagocytophilum and E. chaffeensis in patient and mouse blood and
      ticks by a duplex real-time PCR assay.
AB  - Human granulocytic anaplasmosis (HGA) and human monocytic ehrlichiosis (HME) are
      emerging, tick-borne, zoonotic infectious diseases caused by Anaplasma
      phagocytophilum and Ehrlichia chaffeensis, respectively. Early diagnosis is
      essential for rapid clinical treatment to avoid misdiagnosis and severe patient
      outcomes. Simple, sensitive and reliable diagnostic methods are urgently needed.
      In this study, we developed a duplex real-time PCR assay targeting the A.
      phagocytophilum ankA gene and the E. chaffeensis TRP120 gene, respectively. The
      lowest limit of detection of the duplex real-time PCR assay was 100 copies of the
      targeted A. phagocytophilum ankA gene and the E. chaffeensis TRP120 gene per
      reaction, and the specificity was 100%. Detection in blood DNA samples from the
      acute stage of illness for 22 HGA cases and 8 HME cases indicated that the duplex
      real-time PCR assay was more sensitive than the nested PCR assay. The infection
      of Citellusundulatus Pallas with A. phagocytophilum and E. chaffeensis was first
      confirmed in Xinjiang Province and the positive rate was 3.1% for A.
      phagocytophilum, 6.3% for E. chaffeensis and 3.1% for co-infection with both
      pathogens. The rates of A. phagocytophilum and E. chaffeensis infection of D.
      silvarum ticks collected from Shanxi Province were 8.2% and 14.8%, respectively,
      and the co-infection rate was 3.3%. The rates of A. phagocytophilum and E.
      chaffeensis infection in H. longicornis ticks collected from Shandong Province
      were 1.6% and 6.3%, respectively, and the co-infection rate was 1.6%. 

PMID- 24023964
TI  - Food addiction: its prevalence and significant association with obesity in the
      general population.
AB  - BACKGROUND: 'Food addiction' shares a similar neurobiological and behavioral
      framework with substance addiction. However whether, and to what degree, 'food
      addiction' contributes to obesity in the general population is unknown.
      OBJECTIVES: to assess 1) the prevalence of 'food addiction' in the Newfoundland
      population; 2) if clinical symptom counts of 'food addiction' were significantly
      correlated with the body composition measurements; 3) if food addicts were
      significantly more obese than controls, and 4) if macronutrient intakes are
      associated with 'food addiction'. DESIGN: A total of 652 adults (415 women, 237
      men) recruited from the general population participated in this study. Obesity
      was evaluated by Body Mass Index (BMI) and Body Fat percentage measured by dual
      energy X-ray absorptiometry. 'Food addiction' was assessed using the Yale Food
      Addiction Scale and macronutrient intake was determined from the Willet Food
      Frequency Questionnaire. RESULTS: The prevalence of 'food addiction' was 5.4%
      (6.7% in females and 3.0% in males) and increased with obesity status. The
      clinical symptom counts of 'food addiction' were positively correlated with all
      body composition measurements across the entire sample (p<0.001). Obesity
      measurements were significantly higher in food addicts than controls; Food
      addicts were 11.7 (kg) heavier, 4.6 BMI units higher, and had 8.2% more body fat
      and 8.5% more trunk fat. Furthermore, food addicts consumed more calories from
      fat and protein compared with controls. CONCLUSION: Our results demonstrated that
      'food addiction' contributes to severity of obesity and body composition
      measurements from normal weight to obese individuals in the general population
      with higher rate in women as compared to men.

PMID- 24023965
TI  - Stem cell recruitment of newly formed host cells via a successful seduction?
      Filling the gap between neurogenic niche and injured brain site.
AB  - Here, we report that a unique mechanism of action exerted by stem cells in the
      repair of the traumatically injured brain involves their ability to harness a
      biobridge between neurogenic niche and injured brain site. This biobridge,
      visualized immunohistochemically and laser captured, corresponded to an area
      between the neurogenic subventricular zone and the injured cortex. That the
      biobridge expressed high levels of extracellular matrix metalloproteinases
      characterized initially by a stream of transplanted stem cells, but subsequently
      contained only few to non-detectable grafts and overgrown by newly formed host
      cells, implicates a novel property of stem cells. The transplanted stem cells
      manifest themselves as pathways for trafficking the migration of host neurogenic
      cells, but once this biobridge is formed between the neurogenic site and the
      injured brain site, the grafted cells disappear and relinquish their task to the
      host neurogenic cells. Our findings reveal that long-distance migration of host
      cells from the neurogenic niche to the injured brain site can be achieved through
      transplanted stem cells serving as biobridges for initiation of endogenous repair
      mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to
      date the two major schools of discipline in stem cell repair mechanism primarily
      support the concept of "cell replacement" and bystander effects of "trophic
      factor secretion". The present novel observations of a stem cell seducing a host
      cell to engage in brain repair advances basic science concepts on stem cell
      biology and extracellular matrix, as well as provokes translational research on
      propagating this stem cell-paved biobridge beyond cell replacement and trophic
      factor secretion for the treatment of traumatic brain injury and other
      neurological disorders. 

PMID- 24023966
TI  - Role-play experience facilitates reading the mind of individuals with different
      perception.
AB  - The present study examined effects of role-play experience on reading the mind of
      people with different perception. It is normally difficult but very important in
      daily life to understand people with different characteristics, including those
      with restricted color vision. We explored the mechanisms of reading the mind of
      people with different perception. Forty university students were introduced to a
      communication task in which the use of mindreading was essential. During each
      trial, participants viewed a shelf, presented on a laptop computer, which
      contained several familiar objects, and they were instructed to touch an object
      on the shelf following an instruction issued by a partner who stood at the
      opposite side of the shelf. There were two partners: one was a monkey with normal
      color vision and the other was a dog with restricted color vision. The monkey
      could see all the objects in the same colors as the participants, whereas the dog
      saw some objects in different colors (e.g., he saw as yellow objects that the
      participants saw as red). Participants were required to respond according to the
      partner's instruction. In the restricted color vision condition, the dog saw the
      colors of objects differently; thus, participants had to work out his intentions
      (i.e., mind read), according to his different perspective. In the normal color
      vision condition, all objects were in the same colors as those seen by the
      monkey. Before the test phase, the role-play group had a role-play experience in
      which participants assumed the role of people with restricted color vision. No
      role-play participants made significantly more errors in the restricted color
      vision condition than in the normal color vision condition, whereas among role
      play participants, there was no difference between conditions. These results
      suggest that role-play experience facilitates reading the mind of people with
      perceptual experiences different from our own. 

PMID- 24023967
TI  - Age, sex, and telomere dynamics in a long-lived seabird with male-biased parental
      care.
AB  - The examination of telomere dynamics is a recent technique in ecology for
      assessing physiological state and age-related traits from individuals of unknown
      age. Telomeres shorten with age in most species and are expected to reflect
      physiological state, reproductive investment, and chronological age. Loss of
      telomere length is used as an indicator of biological aging, as this detrimental
      deterioration is associated with lowered survival. Lifespan dimorphism and more
      rapid senescence in the larger, shorter-lived sex are predicted in species with
      sexual size dimorphism, however, little is known about the effects of behavioral
      dimorphism on senescence and life history traits in species with sexual
      monomorphism. Here we compare telomere dynamics of thick-billed murres
      (Urialomvia), a species with male-biased parental care, in two ways: 1) cross
      sectionally in birds of known-age (0-28 years) from one colony and 2)
      longitudinally in birds from four colonies. Telomere dynamics are compared using
      three measures: the telomere restriction fragment (TRF), a lower window of TRF
      (TOE), and qPCR. All showed age-related shortening of telomeres, but the TRF
      measure also indicated that adult female murres have shorter telomere length than
      adult males, consistent with sex-specific patterns of ageing. Adult males had
      longer telomeres than adult females on all colonies examined, but chick telomere
      length did not differ by sex. Additionally, inter-annual telomere changes may be
      related to environmental conditions; birds from a potentially low quality colony
      lost telomeres, while those at more hospitable colonies maintained telomere
      length. We conclude that sex-specific patterns of telomere loss exist in the
      sexually monomorphic thick-billed murre but are likely to occur between fledging
      and recruitment. Longer telomeres in males may be related to their homogamous sex
      chromosomes (ZZ) or to selection for longer life in the care-giving sex.
      Environmental conditions appeared to be the primary drivers of annual changes in
      adult birds. 

PMID- 24023968
TI  - Adoptive transfer of regulatory T cells protects against Coxsackievirus B3
      induced cardiac fibrosis.
AB  - BACKGROUND: Cardiac fibrogenesis in the late stage of viral myocarditis causing
      contractile dysfunction and ventricular dilatation, is a major pathogenic factor
      for the progression of myocarditis to serious cardiovascular diseases including
      dilated cardiomyopathy (DCM) and congestive heart failure (HF). Recent studies
      indicate that regulatory T cells (Tregs) are involved in the fibrotic process of
      liver and lung fibosis. However, the role of Tregs in the development of viral
      myocarditis-caused cardiac fibrosis and their therapeutic potential remains
      unclear. METHODOLOGY/PRINCIPAL FINDINGS: Myocardial fibrosis was induced in
      BALB/c mice by intraperitoneal injection of Coxsackievirus B3 (CVB3) assessed by
      picrosirius red staining and detection of expression levels of collagen I, matrix
      metalloproteinase-1 (MMP-1), matrix metalloproteinase-3 (MMP-3) and tissue
      inhibitor of metalloproteinase-1 (TIMP-1). Myocardial Treg frequency was down
      regulated during the course of viral myocarditis and a negative correlation with
      the severity of cardiac fibrosis was found. To explore the role of Tregs in CVB
      induced cardiac fibrosis, Treg was in vivo depleted by injecting anti-CD25 mAb
      which resulted in aggravation of cardiac fibrosis. In consistent with that, after
      adoptive transfer of isolated Tregs into mice, significant amelioration of CVB3
      induced cardiac fibrosis was confirmed. Interleukin-10 (IL-10) neutralizing
      antibodies were used in vivo and in vitro to explore the molecular mechanism of
      the therapeutic effect of Treg. It was found that administration of anti-IL-10
      mAb after Treg transfer abrogated Treg's treating effect and the inhibition of
      Treg on collagen production by cardiac fibroblasts was mediated mainly through IL
      10. CONCLUSION/SIGNIFICANCE: Our data suggested that Tregs have a protective role
      in the fibrotic process of CVB3-induced cardiac fibrosis via secreting IL-10 and
      might provide an alternative option for the future treatment of cardiac fibrosis.

PMID- 24023969
TI  - Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine
      modification and decreased CTCF binding at the FXN locus.
AB  - BACKGROUND: Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat
      expansion mutation within intron 1 of the FXN gene, which induces epigenetic
      changes and FXN gene silencing. Bisulfite sequencing studies have identified 5
      methylcytosine (5 mC) DNA methylation as one of the epigenetic changes that may
      be involved in this process. However, analysis of samples by bisulfite sequencing
      is a time-consuming procedure. In addition, it has recently been shown that 5
      hydroxymethylcytosine (5 hmC) is also present in mammalian DNA, and bisulfite
      sequencing cannot distinguish between 5 hmC and 5 mC. METHODOLOGY/PRINCIPAL
      FINDINGS: We have developed specific MethylScreen restriction enzyme digestion
      and qPCR-based protocols to more rapidly quantify DNA methylation at four CpG
      sites in the FXN upstream GAA region. Increased DNA methylation was confirmed at
      all four CpG sites in both FRDA cerebellum and heart tissues. We have also
      analysed the DNA methylation status in FRDA cerebellum and heart tissues using an
      approach that enables distinction between 5 hmC and 5 mC. Our analysis reveals
      that the majority of DNA methylation in both FRDA and unaffected tissues actually
      comprises 5 hmC rather than 5 mC. We have also identified decreased occupancy of
      the chromatin insulator protein CTCF (CCCTC-binding factor) at the FXN 5' UTR
      region in the same FRDA cerebellum tissues. CONCLUSIONS/SIGNIFICANCE: Increased
      DNA methylation at the FXN upstream GAA region, primarily 5 hmC rather than 5 mC,
      and decreased CTCF occupancy at the FXN 5' UTR are associated with FRDA disease
      relevant human tissues. The role of such molecular mechanisms in FRDA
      pathogenesis has now to be determined.

PMID- 24023970
TI  - The role of mitochondria-derived reactive oxygen species in hyperthermia-induced
      platelet apoptosis.
AB  - A combination of hyperthermia with radiotherapy and chemotherapy for various
      solid tumors has been practiced clinically. However, hyperthermic therapy has
      side effects, such as thrombocytopenia. Up to now, the pathogenesis of
      hyperthermia-induced thrombocytopenia remains unclear. Previous studies have
      shown that hyperthermia induces platelet apoptosis. However, the signaling
      pathways and molecular mechanisms involved in hyperthermia-induced platelet
      apoptosis have not been determined. Here we show that hyperthermia induced
      intracellular reactive oxygen species (ROS) production and mitochondrial ROS
      generation in a time-dependent manner in platelets. The mitochondria-targeted ROS
      scavenger Mito-TEMPO blocked intracellular ROS and mitochondrial ROS generation.
      By contrast, inhibitors of reduced nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase, nitric oxide synthase, cyclooxygenase and lipoxygenase did not.
      Furthermore, Mito-TEMPO inhibited hyperthermia-induced malonyldialdehyde
      production and cardiolipin peroxidation. We also showed that hyperthermia
      triggered platelet apoptosis was inhibited by Mito-TEMPO. Furthermore, Mito-TEMPO
      ameliorated hyperthermia-impaired platelet aggregation and adhesion function.
      Lastly, hyperthermia decreased platelet manganese superoxide dismutase (MnSOD)
      protein levels and enzyme activity. These data indicate that mitochondrial ROS
      play a pivotal role in hyperthermia-induced platelet apoptosis, and decreased of
      MnSOD activity might, at least partially account for the enhanced ROS levels in
      hyperthermia-treated platelets. Therefore, determining the role of mitochondrial
      ROS as contributory factors in platelet apoptosis, is critical in providing a
      rational design of novel drugs aimed at targeting mitochondrial ROS. Such
      therapeutic approaches would have potential clinical utility in platelet
      associated disorders involving oxidative damage. 

PMID- 24023971
TI  - The bacterial carbon-fixing organelle is formed by shell envelopment of
      preassembled cargo.
AB  - BACKGROUND: Cyanobacteria play a significant role in the global carbon cycle. In
      Synechococcuselongatus, the carbon-fixing enzyme ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RuBisCO) is concentrated into polyhedral, proteinaceous
      compartments called carboxysomes. METHODOLOGY/PRINCIPAL FINDINGS: Using live cell
      fluorescence microscopy, we show that carboxysomes are first detected as small
      seeds of RuBisCO that colocalize with existing carboxysomes. These seeds contain
      little or no shell protein, but increase in RuBisCO content over several hours,
      during which time they are exposed to the solvent. The maturing seed is then
      enclosed by shell proteins, a rapid process that seals RuBisCO from the cytosol
      to establish a distinct, solvent-protected microenvironment that is oxidizing
      relative to the cytosol. These closure events can be spatially and temporally
      coincident with the appearance of a nascent daughter RuBisCO seed.
      CONCLUSIONS/SIGNIFICANCE: Carboxysomes assemble in a stepwise fashion, inside-to
      outside, revealing that cargo is the principle organizer of this compartment's
      biogenesis. Our observations of the spatial relationship of seeds to previously
      formed carboxysomes lead us to propose a model for carboxysome replication via
      sequential fission, polymerization, and encapsulation of their internal cargo.

PMID- 24023973
TI  - Review of facial nerve anatomy: trauma to the temporal region.

PMID- 24023972
TI  - Computed tomography angiography in microsurgery: indications, clinical utility,
      and pitfalls.
AB  - OBJECTIVE: Computed tomographic angiography (CTA) can be used to obtain 3
      dimensional vascular images and soft-tissue definition. The goal of this study
      was to evaluate the reliability, usefulness, and pitfalls of CTA in preoperative
      planning of microvascular reconstructive surgery. METHODS: A retrospective review
      of patients who obtained preoperative CTA in preparation for planned
      microvascular reconstruction was performed over a 5-year period (2001-2005). The
      influence of CTA on the original operative plan was assessed for each patient,
      and CTA results were correlated to the operative findings. RESULTS: Computed
      tomographic angiography was performed on 94 patients in preparation for
      microvascular reconstruction. In 48 patients (51%), vascular abnormalities were
      noted on CTA. Intraoperative findings correlated with CTA results in 97% of
      cases. In 42 patients (45%), abnormal CTA findings influenced the original
      operative plan, such as the choice of vessels, side of harvest, or nature of the
      reconstruction (local flap instead of free tissue transfer). Technical
      difficulties in performing CTA were encountered in 5 patients (5%) in whom
      interference from external fixation devices was the main cause. CONCLUSIONS: This
      large study of CTA obtained for preoperative planning of reconstructive
      microsurgery at both donor and recipient sites study demonstrates that CTA is
      safe and highly accurate. Computed tomographic angiography can alter the
      surgeon's reconstructive plan when abnormalities are noted preoperatively and
      consequently improve results by decreasing vascular complication rates. The use
      of CTA should be considered for cases of microsurgical reconstruction where the
      vascular anatomy may be questionable.

PMID- 24023974
TI  - Fat grafting breast augmentation mammaplasty.

PMID- 24023975
TI  - High-intensity focused ultrasound in aesthetic plastic surgery.

PMID- 24023976
TI  - Low-dose cyclophosphamide-induced acute hepatotoxicity.
AB  - PATIENT: Male, 48 FINAL DIAGNOSIS: Low dose cyclophosphamide-induced acute
      hepatotoxicity Symptoms: Epigastric pain Medication: Withdrawal of
      cyclophosphamide Clinical Procedure: - Specialty: Nephrology * Hepatology *
      Gastroenterology * Toxicology. OBJECTIVE: Unexpected drug reaction. BACKGROUND:
      Cyclophosphamide is commonly used to treat cancers, systemic vasculitides, and
      kidney diseases (e.g., lupus nephritis and focal segmental glomerulosclerosis).
      Acute adverse effects include bone marrow suppression, hemorrhagic cystitis,
      nausea, vomiting, and hair loss. Hepatotoxicity with high dose cyclophosphamide
      is well recognized but hepatitis due to low dose cyclophosphamide has rarely been
      described. CASE REPORT: We report the case of a 48-year-old Chinese man with a
      rapidly progressive glomerulonephritis secondary to granulomatosis with
      polyangiitis who developed severe acute hepatic failure within 24 hours of
      receiving low-dose intravenous cyclophosphamide. The diagnosis of granulomatosis
      with polyangiitis was supported with a positive c-ANCA serology. The patient was
      treated with high dose methylprednisolone, plasmapheresis, intermittent
      hemodialysis, and low-dose intravenous cyclophosphamide. CONCLUSIONS:
      Hepatotoxicity may occur even after low-dose intravenous cyclophosphamide
      treatment. To the best of our knowledge, this is the first report of severe, non
      viral, liver inflammation developing within 24 hours of administration of low
      dose intravenous cyclophosphamide (200 mg). Physicians should be aware of this
      serious adverse reaction and should not repeat the cyclophosphamide dose when
      there is hepatotoxicity caused by the first dose. Initial and follow-up liver
      function tests should be monitored in all patients receiving cyclophosphamide
      treatment.

PMID- 24023977
TI  - Postobstructive pulmonary edema following accidental near-hanging.
AB  - PATIENT: Female, 14 FINAL DIAGNOSIS: Postobstructive pulmonary edenma Symptoms:
      Chest indrawing * bilateral pulmonary crepitations * tachypnea MEDICATION: -
      Clinical Procedure: Controlled ventilatory support * positive end expiratory
      pressure Specialty: Intensive care. OBJECTIVE: Unusual clinical course.
      BACKGROUND: Postobstructive pulmonary edema (POPE) is a life-threatening
      complication that occurs after the relief of an upper airway obstruction. POPE
      occurs rarely in children, primarily after non-lethal hanging. CASE REPORT: We
      report the case of a 14-year-old girl who developed POPE after accidental near
      hanging. She had chest in-drawing, the SpO2 was 81% on room air, and pulmonary
      auscultation revealed bilateral crepitations. The chest x-ray showed bilateral
      diffuse infiltrates consistent with pulmonary edema. The intensive care
      management consisted of controlled ventilatory support with high-level positive
      end expiratory pressure. On the third day of hospitalization, the patient was
      weaned from the ventilator and extubated with a full recovery. CONCLUSIONS: This
      case confirms the importance of early recognition of POPE and the value of
      adapted treatment, which can lead to a favorable outcome and full recovery in
      cases of near hanging.

PMID- 24023978
TI  - Saccharomyces cerevisiae linker histone-Hho1p maintains chromatin loop
      organization during ageing.
AB  - Intricate, dynamic, and absolutely unavoidable ageing affects cells and organisms
      through their entire lifetime. Driven by diverse mechanisms all leading to
      compromised cellular functions and finally to death, this process is a challenge
      for researchers. The molecular mechanisms, the general rules that it follows, and
      the complex interplay at a molecular and cellular level are yet little
      understood. Here, we present our results showing a connection between the linker
      histones, the higher-order chromatin structures, and the process of chronological
      lifespan of yeast cells. By deleting the gene for the linker histone in
      Saccharomyces cerevisiae we have created a model for studying the role of
      chromatin structures mainly at its most elusive and so far barely understood
      higher-order levels of compaction in the processes of yeast chronological
      lifespan. The mutant cells demonstrated controversial features showing slower
      growth than the wild type combined with better survival during the whole process.
      The analysis of the global chromatin organization during different time points
      demonstrated certain loss of the upper levels of chromatin compaction in the
      cells without linker histone. The results underlay the importance of this histone
      for the maintenance of the chromatin loop structures during ageing. 

PMID- 24023979
TI  - Neurologic complications after liver transplantation.
AB  - Neurologic complications are relatively common after solid organ transplantation
      and affect 15%-30% of liver transplant recipients. Etiology is often related to
      immunosuppressant neurotoxicity and opportunistic infections. Most common
      complications include seizures and encephalopathy, and occurrence of central
      pontine myelinolysis is relatively specific for liver transplant recipients.
      Delayed allograft function may precipitate hepatic encephalopathy and
      neurotoxicity of calcineurin inhibitors typically manifests with tremor,
      headaches and encephalopathy. Reduction of neurotoxic immunosuppressants or
      conversion to an alternative medication usually result in clinical improvement.
      Standard preventive and diagnostic protocols have helped to reduce the prevalence
      of opportunistic central nervous system (CNS) infections, but viral and fungal
      CNS infections still affect 1% of liver transplant recipients, and the morbidity
      and mortality in the affected patients remain fairly high. Critical illness
      myopathy may also affect up to 7% of liver transplant recipients. Liver
      insufficiency is also associated with various neurologic disorders which may
      improve or resolve after successful liver transplantation. Accurate diagnosis and
      timely intervention are essential to improve outcomes, while advances in clinical
      management and extended post-transplant survival are increasingly shifting the
      focus to chronic post-transplant complications which are often encountered in a
      community hospital and an outpatient setting. 

PMID- 24023980
TI  - Imaging appearance of treated hepatocellular carcinoma.
AB  - Surgical resection and imaging guided treatments play a crucial role in the
      management of hepatocellular carcinoma (HCC). Although the primary end point of
      treatment of HCC is survival, radiological response could be a surrogate end
      point of survival, and has a key role in HCC decision-making process. However,
      radiological assessment of HCC treatment efficacy is often controversial. There
      are few doubts on the evaluation of surgical resection; in fact, all known tumor
      sites should be removed. However, an unenhancing partial linear peripheral halo,
      in most cases, surrounding a fluid collection reducing in size during follow-up
      is demonstrated in successfully resected tumor with bipolar radiofrequency
      electrosurgical device. Efficacy assessment of locoregional therapies is more
      controversial and differs between percutaneous ablation (e.g., radiofrequency
      ablation and percutaneous ethanol injection) and transarterial treatments (e.g.,
      conventional transarterial chemoembolization, transarterial chemoembolization
      with drug eluting beads and radioembolization). Finally, a different approach
      should be used for new systemic agent that, though not reducing tumor mass, could
      have a benefit on survival by delaying tumor progression and death. The purpose
      of this brief article is to review HCC imaging appearance after treatment. 

PMID- 24023981
TI  - Participation of peribiliary glands in biliary tract pathophysiologies.
AB  - AIM: To investigate the roles of peribiliary glands around the bile ducts in the
      pathophysiology of the biliary tract. METHODS: The expression of fetal pancreatic
      markers, pancreatic duodenal homeobox factor 1 (PDX1) and hairy and enhancer of
      split 1 (HES1) and endodermal stem/progenitor (S/P) cell markers [CD44s,
      chemokine receptor type 4 (CXCR4), SOX9 and epithelial cell adhesion molecule
      (EpCAM)] were examined immunohistochemically in 32 normal adult livers (autopsy
      livers) and 22 hepatolithiatic livers (surgically resected livers). The latter
      was characterized by the proliferation of the peribiliary glands.
      Immunohistochemistry was performed using formalin-fixed, paraffin-embedded tissue
      sections after deparaffinization. Although PDX1 and HES1 were expressed in both
      the nucleus and cytoplasm of epithelial cells, only nuclear staining was
      evaluated. SOX9 was expressed in the nucleus, while CD44s, CXCR4 and EpCAM were
      expressed in the cell membranes. The frequency and extent of the expression of
      these molecules in the lining epithelia and peribiliary glands were evaluated
      semi-quantitatively based on the percentage of positive cells: 0, 1+ (focal), 2+
      (moderate) and 3+ (extensive). RESULTS: In normal livers, PDX1 was infrequently
      expressed in the lining epithelia, but was frequently expressed in the
      peribiliary glands. In contrast, HES1 was frequently expressed in the lining
      epithelia, but its expression in the peribiliary glands was focal, suggesting
      that the peribiliary glands retain the potential of differentiation toward the
      pancreas and the lining epithelia exhibit properties to inhibit such
      differentiation. This unique combination was also seen in hepatolithiatic livers.
      The expression of endodermal S/P cell markers varied in the peribiliary glands in
      normal livers: SOX9 and EpCAM were frequently expressed, CD44s infrequently, and
      CXCR4 almost not at all. The expression of these markers, particularly CD44s and
      CXCR4, increased in the peribiliary glands and lining epithelia in
      hepatolithiatic livers. This increased expression of endodermal S/P cell markers
      may be related to the increased production of intestinal and gastric mucin and
      also to the biliary neoplasia associated with the gastric and intestinal
      phenotypes reported in hepatolithiasis. CONCLUSION: The unique expression pattern
      of PDX1 and HES1 and increased expression of endodermal S/P cell markers in the
      peribiliary glands may be involved in biliary pathophysiologies.

PMID- 24023982
TI  - Can non-invasive measurements aid clinical assessment of volume in patients with
      cirrhosis?
AB  - AIM: To evaluate the non-invasive assessments of volume status in patients with
      cirrhosis. METHODS: Echocardiography and multifrequency bioimpedance analysis
      measurements and short synacthen tests were made in 20 stable and 25 acutely
      decompensated patients with cirrhosis. RESULTS: Both groups had similar clinical
      assessments, cortisol response and total body water (TBW), however the ratio of
      extracellular water (ECW)/TBW was significantly greater in the trunk (0.420 +/-
      0.004 vs 0.404 +/- 0.005), and limbs (R leg 0.41 +/- 0.003 vs 0.398 +/- 0.003, P
      < 0.05, and L leg 0.412 +/- 0.003 vs 0.399 +/- 0.003) with decompensated
      cirrhosis compared to stable cirrhotics, P < 0.05). Echocardiogram derived right
      atrial and ventricular filling and end diastolic pressures and presence of
      increased left ventricular end diastolic volume and diastolic dysfunction were
      similar in both groups. The decompensated group had lower systemic blood
      pressure, mean systolic 101.8 +/- 4.3 vs 122.4 +/- 5.3 and diastolic 58.4 +/- 4.1
      mmHg vs 68.8 +/- 3.1 mmHg respectively, P < 0.01, and serum albumin 30 (27-33) vs
      32 (31-40.5) g/L, P < 0.01. CONCLUSION: Decompensated cirrhotics had greater leg
      and truncal ECW expansion with lower serum albumin levels consistent with
      intravascular volume depletion and increased vascular permeability.

PMID- 24023983
TI  - Noninvasive assessment of liver damage in chronic hepatitis B.
AB  - AIM: To evaluate the efficacy of the aspartate aminotransferase/platelet ratio
      index (APRI) and neutrophil-lymphocyte (N/L) ratio to predict liver damage in
      chronic hepatitis B (CHB). METHODS: We analyzed 89 patients diagnosed with CHB by
      percutaneous liver biopsy and 43 healthy subjects. Liver biopsy materials were
      stained with hematoxylin-eosin and Masson's trichrome. Patients' fibrosis scores
      and histological activity index (HAI) were calculated according to the Ishak
      scoring system. Fibrosis score was recognized as follows: F0-1 No /early-stage
      fibrosis, F2-6 significant fibrosis, F0-4 non-cirrhotic and F5-6 cirrhotic.
      Significant liver fibrosis was defined as an Ishak score of >= 2. APRI and N/L
      ratio calculation was made by blood test results. RESULTS: The hepatitis B and
      control group showed no difference in N/L ratios while there was a significant
      difference in terms of APRI scores (P < 0.001). Multiple logistic regression
      analysis revealed that the only independent predictive factor for liver fibrosis
      in CHB was platelet count. APRI score was significantly higher in cirrhotic
      patients than in non-cirrhotic patients. However, this significance was not
      confirmed by multiple logistic regression analysis. The optimum APRI score cut
      off point to identify patients with cirrhosis was 1.01 with sensitivity,
      specificity, positive predictive value and negative predictive value of 62% (36%
      86%), 74% (62%-83%), 29% (13%-49%) and 92% (82%-97%), respectively. In addition,
      correlation analyses revealed that N/L ratio has a negative and significant
      relationship with HAI (r = -0.218, P = 0.041). CONCLUSION: N/L ratio was
      negatively correlated with HAI. APRI score may be useful to exclude cirrhosis in
      CHB patients.

PMID- 24023984
TI  - Serum complement C4a and its relation to liver fibrosis in children with chronic
      hepatitis C.
AB  - AIM: To evaluate serum complement C4a and its relation to liver fibrosis in
      children with chronic hepatitis C virus (HCV) infection. METHODS: The study
      included 30 children with chronic HCV infection before receiving antiviral
      therapy. Chronic HCV infection was defined by positive anti-HCV, a positive
      polymerase chain reaction for HCV-RNA for more than 6 mo with absence of any
      associated liver disease. A second group of 30 age- and sex-matched healthy
      children served as controls. Serum C4a levels were measured by enzyme-linked
      immunosorbent assay. Liver fibrosis stage and inflammatory grade were assessed
      using Ishak scoring system. Serum C4a levels were compared according to different
      clinical, laboratory and histopathological parameters. Statistical significance
      for quantitative data was tested by Mann-Whitney U non-parametric tests. For
      qualitative data, significance between groups was tested by chi(2) test.
      Correlation was tested by Spearman's test. Results were considered significant if
      P value <= 0.05. RESULTS: The age of the patients ranged from 3.5 to 18 years and
      that of controls ranged from 4 to 17 years. C4a mean levels were merely lower in
      patients (153.67 +/- 18.69 mg/L) than that in the controls (157.25 +/- 11.40
      mg/L) with no statistical significance (P = 0.378). It did not differ
      significantly in patients with elevated vs those with normal transaminases
      (152.25 +/- 16.62 vs 155.36 +/- 21.33; P = 0.868) or with different HCV viremia
      (P = 0.561). Furthermore, there was no statistical significant difference in
      serum levels between those with no/mild fibrosis and those with moderate fibrosis
      (154.65 +/- 20.59 vs 152.97 +/- 17.72; P = 0.786) or minimal and mild activity
      (155.1 +/- 21.93 vs 152.99 +/- 17.43; P = 0.809). Though statistically not
      significant, C4a was highest in fibrosis score 0 (F0), decreasing in F1 and F2 to
      be the lowest in F3. When comparing significant fibrosis (Ishak score >= 3) vs
      other stages, C4a was significantly lower in F3 compared to other fibrosis scores
      (143.55 +/- 2.33 mg/L vs 155.26 +/- 19.64 mg/L; P = 0.047) and at a cutoff value
      of less than 144.01 mg/L, C4a could discriminate F3 with 76.9% sensitivity and
      75% specificity from other stages of fibrosis. CONCLUSION: Serum complement C4a
      did not correlate with any of transaminases, HCV viremia or with the
      histopathological scores. Although C4a decreased with higher stages of fibrosis,
      this change was not significant enough to predict individual stages of fibrosis.
      Yet, it could predict significant fibrosis with acceptable clinical performance.

PMID- 24023985
TI  - Alcohol and tobacco misuse: Reducing aerodigestive cancer risk.
AB  - Significant concerns over the health, social and economic burdens of the two most
      common, and frequently co-misused drugs of abuse, alcohol and tobacco, has
      encouraged focused but separate health promotion and disease prevention policies.
      However, this separation of focus means that while individuals who present with
      alcohol-related problems are increasingly supported to attain and maintain
      abstinence from alcohol they are not routinely assisted to refrain from smoking.
      This is tragically inopportune as alcohol and tobacco have an established
      "synergistic" effect on aerodigestive cancer risk. Moreover, even when patients
      successfully tackle their alcohol problems they remain at increased risk for
      developing these cancers, especially if they continue to smoke. A case series is
      presented together with a discussion on how service provision for co-misuse could
      be improved to obviate aerodigestive cancer risk. Given the prevalence of alcohol
      and tobacco use in the United Kingdom, these observations may have far reaching
      implications for the individual, health provider(s) and wider society. 

PMID- 24023986
TI  - A novel alpha1-antitrypsin null variant (PiQ0Milano ).
AB  - Alpha1-antitrypsin deficiency is an autosomal recessive disease characterized by
      reduced serum levels of alpha1-antitrypsin (AAT) due to mutations in the SERPINA1
      gene causing early onset pulmonary emphysema and, occasionally, chronic liver
      disease. We report an incidental finding of a novel null AAT allele, Q0Milano,
      consisting of a 17 nucleotides deletion in exon 3 of SERPINA1 gene, in an Italian
      child with persistently increased liver enzymes, a mild decrease in circulating
      AAT levels and without any pulmonary disease. Q0Milano variant results in an
      unfunctional protein lacking of AAT active site, as the resultant protein is
      truncated near PiS locus involved in AAT protein stability. 

PMID- 24023988
TI  - Soft tissue infection caused by Legionella bozemanii in a patient with ongoing
      immunosuppressive treatment.
AB  - The Legionellaceae family consists of approximately 50 species, of which the most
      commonly identified species is L. pneumophila, the causative agent of
      Legionnaires' disease. Other Legionella ssp. most often cause clinical infections
      in the immune-compromised patients, in which L. bozemanii has been known to cause
      both pneumonia and lung abscesses. In the presented case, a soft tissue infection
      in a patient with ongoing immunosuppression was determined to be due to L.
      bozemanii. Hence, in immune-deficient patients, L. bozemanii could be considered
      a possible agent in soft tissue infections when other common pathogens have been
      ruled out. 

PMID- 24023989
TI  - Spinal cord stimulation: panacea for incurable diseases?

PMID- 24023990
TI  - Appropriate design of research and statistical analyses: observational versus
      experimental studies.

PMID- 24023991
TI  - Effect of preoperative anxiety on spectral entropy during induction with
      propofol.
AB  - BACKGROUND: Anxiety influences brain wave activity. E-Entropy module-derived
      spectral entropy is an electroencephalographic derivative used to monitor the
      depth of sedation. This study assessed the effect of preoperative anxiety on the
      spectral entropy parameters of response entrophy (RE) and state entrophy (SE).
      METHODS: Trait anxiety was measured in 92 American Society of Anesthesiologists
      physical status I-II patients with the Spielberger State-Trait Anxiety Inventory
      (STAI) form X2 and state anxiety with STAI-X1 just before anesthesia. RE, SE,
      blood pressure and heart rate were measured before induction. Propofol was
      infused via a target controlled infusion pump. At loss of consciousness (LOC),
      the effect-site concentration (Ce), RE, SE and total amount of propofol were
      recorded. Patients were stratified into three groups based on their state and
      trait anxiety scores to evaluate the effect of anxiety level on entropy values.
      RESULTS: STAI-X1 was significantly correlated with RE and SE for LOC (rho =
      0.230, P = 0.028 and rho = 0.308, P = 0.003, respectively) and also with STAI-X2
      (rho = 0.411, P = 0.001, respectively). SE was higher in the high state anxiety
      group than in the low state anxiety group (P = 0.017). The other measured
      variables were not correlated with any anxiety scales. CONCLUSIONS: The state of
      anxiety increases RE and SE values at LOC induced with propofol. High state
      anxiety is associated with higher SE than apparent at low state anxiety. When
      determining the propofol-induced LOC by spectral entropy, anxiety levels should
      be considered.

PMID- 24023992
TI  - Preanesthetic dexmedetomidine 1 ug/kg single infusion is a simple, easy, and
      economic adjuvant for general anesthesia.
AB  - BACKGROUND: Dexmedetomidine is an alpha2-adrenoreceptor agonist with sedative,
      analgesic and anxiolytic effects, and it has more selective alpha2-adrenergic
      effect than clonidine. We evaluate the effect of preansethetic dexmedetomidine 1
      ug/kg single infusion on sedation, hemodynamics, anesthetic consumption, and
      recovery profiles during anesthesia. METHODS: Forty-two female patients with
      American Society of Anesthesiologists physical status I or II undergoing
      gynecologic surgery with anticipated operation time of 2 h, were randomly
      assigned to receive dexmedetomidine 1 ug/kg (Dex group) or saline (control group)
      iv over 10 min before anesthetic induction. After tracheal intubation with
      propofol 2 mg/kg, cisatracurium 0.15 mg/kg iv, anesthesia was maintained with
      sevoflurane, O2 50%, N2O 50% around a BIS value of 40. RESULTS: After study drug
      infusion, BIS of Dex group was lower than that of control group (93.9 +/- 3.1 vs
      51.5 +/- 5.2, P < 0.05). Mean arterial pressure (MAP) and heart rate (HR) after
      intubation were increased in control group, but did not change in Dex group.
      During maintenance, there was no difference in MAP between groups, but HR of Dex
      group was lower compared to that of control group. End-tidal concentration (2.0
      +/- 0.5 vol% vs 1.4 +/- 0.3 vol%, P < 0.05) and total cumulative consumption of
      sevoflurane (34.6 +/- 3.8 ml vs 26.5 +/- 5.3 ml, P < 0.05) were lower in Dex
      group than in control group. Recovery profiles, modified Aldrete score,
      postoperative nausea vomiting, and visual analogue pain score were not
      significantly different between groups. CONCLUSIONS: Preanesthetic dexmetomidine
      1 ug/kg single infusion is a simple, easy, and economic general anesthetic
      adjuvant that maintains stable hemodynamics and decrease anesthetic consumption
      without the change of recovery profiles.

PMID- 24023993
TI  - The determinants of propofol induction time in anesthesia.
AB  - BACKGROUND: The required dose of anesthetics is generally smaller in patients
      with low cardiac output (CO). A high CO decreases the blood concentration of
      anesthetics during induction and maintenance of anesthesia. However, a high CO
      may also shorten the delivery time of anesthetics to the effect site, e.g. the
      brain. We assessed the time required for induction of anesthesia with propofol
      administered by target-controlled infusion (TCI), and investigated factors that
      modify the pharmacodynamics of propofol. METHODS: After measuring CO and blood
      volume (BV) by dye densitometry, propofol was infused using TCI to simulate a
      plasma concentration of 3 ug/ml. After infusion, the time taken to achieve
      bispectral index (BIS) values of 80 and 60 was determined. Age, sex, lean body
      mass (LBM), and cardiovascular parameters were analyzed as independent variables.
      The dependent variables were the time taken to achieve each BIS value and the
      plasma concentration of propofol (Cp) 10 min after the commencement of infusion.
      RESULTS: Multiple regression analysis revealed that a high CO significantly
      reduced the time taken to reach the first end point (P = 0.020, R(2) = 0.076).
      Age and LBM significantly prolonged the time taken to reach the second end point
      (P = 0.001). Cp was negatively correlated with BV (P = 0.020, R(2) = 0.073).
      CONCLUSIONS: Cardiac output was a statistically significant factor for predicting
      the time required for induction of anesthesia in the initial phase, whereas, age
      and LBM were significant variables in the late phase. The pharmacodynamics of
      propofol was intricately altered by CO, age, and LBM.

PMID- 24023994
TI  - Jaw-thrust induces sympathetic responses during induction of general anesthesia.
AB  - BACKGROUND: Jaw-thrust is a noxious stimulus that might induce sympathetic
      responses. The purpose of this study, was to evaluate the effects of jaw-thrust
      on sympathetic responses. METHODS: We investigated seventy three patients.
      Patients who received general anesthesia were randomly divided into a control
      group (maintenance of combined airway maneuver with head tilt, open mouth by
      mouthpiece, and chin-lift, n = 30) and jaw-thrust group (maintenance of head
      tilt, open mouth and jaw-thrust, n = 30). In the jaw-thrust group, four minutes
      of endoscopy-guided force to the mandible to get the best laryngeal view were
      applied. For the control group, the combined airway maneuver was maintained
      during the same period. Arterial blood pressure (AP) and heart rate (HR) were
      recorded at predetermined time points (1 min before anesthesia induction, 2 min
      after fiberoptic bronchoscopy placement, and thereafter 1 min-interval during
      each airway maneuver) during jaw-thrust and chin-lift maneuver. The force
      amplitude applied for best laryngeal view during jaw-thrust was also measured.
      RESULTS: Peak systolic and diastolic AP increased 39.0 +/- 17.6 and 39.9 +/- 22.8
      mmHg from the baseline (P < 0.001) in the jaw-thrust group. HR was also 32.5 +/-
      19.4 beats/min from the baseline (P < 0.001) in the jaw-thrust group. These
      remained high at all time points, compared with the control group (P < 0.01). The
      force magnitude applied for jaw-thrust was not correlated to the AP and HR
      changes (P > 0.05). CONCLUSIONS: Performing the jaw-thrust maneuver induces
      significant sympathetic responses, irrespective of the force magnitude.

PMID- 24023995
TI  - The effect of xylometazoline spray for expansion of nasal cavity.
AB  - BACKGROUND: During nasotracheal intubation it is important to have proper
      pretreatment for nasal mucosa constriction and nasal cavity expanding. Nasal
      packing of epinephrine gauze is widely used as well as xylometazoline. The aim of
      this study was to compare and evaluate the efficacy of prophylactic intranasal
      spray of xylometazoline against epinephrine gauze packing in expanding the nasal
      cavity. METHODS: Volunteers (n = 32) in their twenties without nasal disease such
      as septal deviation or rhinitis were enrolled in the study. The more patent
      nostril in each subject was measured by acoustic rhinometry as the base value.
      After intranasal spray of xylometazoline, the same nostril was remeasured by same
      method. Twenty four hours later, intranasal packing of epinephrine gauze was done
      and the same treatment was done. Subject preferences about the procedures were
      asked. RESULTS: THERE WERE SIGNIFICANT DIFFERENCE AMONG TREATMENTS (BASE VALUE:
      0.582 +/- 0.164 cm(2), xylometazoline spray: 0.793 +/- 0.165 cm(2), epinephrine
      gauze packing: 0.990 +/- 0.290 cm(2)) in acoustic rhinometry. While the
      epinephrine gauze packing showed more efficient mucosa constriction, subjects
      preferred xylometazoline spray. CONCLUSIONS: Even though xylometazoline spray was
      less effective than epinephrine gauze packing, the simplicity and convenience
      compensated. In patients undergoing nasotracheal intubation, xylometazoline spray
      can be an alternative to epinephrine gauze packing.

PMID- 24023996
TI  - Perioperative respiratory adverse events in children with active upper
      respiratory tract infection who received general anesthesia through an
      orotracheal tube and inhalation agents.
AB  - BACKGROUND: Active upper respiratory tract infection (URI), orotracheal
      intubation and use of inhalation anesthetics are known risk factors for
      perioperative respiratory adverse events (RAE). This study investigated the risk
      factors of perioperative RAE in children with these risk factors. METHODS: The
      records of 159 children who underwent general anesthesia with an orotracheal tube
      and inhalation were reviewed. These patients also had at least one of the
      following URI symptoms on the day of surgery: clear or green nasal secretion, dry
      or moist cough, nasal congestion, or fever. RAE such as laryngospasm,
      bronchospasm, oxygen desaturation and sustained cough were collected before
      induction, during intubation, during extubation, after extubation and in the
      postanesthesia care unit. RESULTS: Forty-five patients had RAE. The patients with
      RAE were younger than those without RAE. There were more passive smokers and a
      greater number of intubation attempts in patients with RAE than in those without
      RAE. The type of surgery and type of inhalation agents were not different between
      patients with and without RAE. Passive smoking was the only independent risk
      factor for RAE. CONCLUSIONS: In children with an active URI using orotracheal
      tube and inhalation anesthetics, passive smoking is an important risk factor for
      RAE.

PMID- 24023997
TI  - The impact of remifentanil on incidence and severity of postoperative nausea and
      vomiting in a university hospital-based ambulatory surgery center: a
      retrospective observation study.
AB  - BACKGROUND: Ambulatory surgery, including short-stay surgery, has become a common
      choice in clinical practice. For the success of ambulatory surgery, perioperative
      care with safe and effective anesthesia and postoperative analgesia, which can
      reduce the occurrence of postoperative nausea and vomiting (PONV), is essential.
      The effect of remifentanil on the occurrence and severity of PONV has not been
      thoroughly examined, particularly, in an ambulatory surgery setting. Here, we
      investigate whether remifentanil influences the occurrence and severity of PONV
      in a university hospital-based ambulatory unit. METHODS: We retrospectively
      analyzed a total of 1,765 cases of patients who had undergone general anesthesia
      at our ambulatory surgery unit. Parameters, such as occurrence and severity of
      nausea, vomiting or retching, use of antiemetic drugs, amount of postoperative
      analgesic and patient satisfaction, were extracted from the records and analyzed
      between the groups that received and not received remifentanil. RESULTS: Within
      565 patients of the RF group, 39 patients (6.6%) experienced nausea, 7 patients
      (1.2%) experienced vomiting or retching, and 10 patients (1.8%) were given
      antiemetic; in addition, the maximum VAS value for nausea was 12.1 mm. In 1,200
      patients of the non RF group, 102 patients (8.5%) experienced nausea, 19 patients
      (1.6%) experienced vomiting or retching, and 34 patients (2.8%) were given
      antiemetic, and the maximum VAS value was 13.2 mm. There were no statistically
      significant differences between the two groups. CONCLUSIONS: Our results indicate
      that remifentanil did not increase the occurrence of PONV in patients within the
      ambulatory surgery unit.

PMID- 24023998
TI  - Anaphylactic reactions after cisatracurium administration in two patients -a
      report of two cases-.
AB  - Cisatracurium was initially characterized to have no evident histamine-releasing
      potential with excellent cardiovascular stability. However, severe anaphylactic
      reactions to cisatracurium that resulted in bronchospasms and cardiovascular
      collapse have been reported worldwide. Two cases of severe anaphylactic reactions
      after the administration of cisatracurium are presented. The anesthetics used in
      both cases were lidocaine, midazolam, propofol (microemulsion propofol in the
      second case), remifentanil and cisatracurium. After the administration of these
      drugs, bronchospasm and hypotension manifested, leading to the diagnosis of
      anaphylaxis and appropriate treatment. Skin intradermal testing confirmed that
      both cases were due to immune-mediated anaphylaxis to cisatracurium, despite the
      fact that neither of the patients had been exposed to the allergen previously.
      The anaphylaxis may be due to cross-reactivity between neuromuscular blocking
      agents and substances with quaternary ammonium ions. Anesthesiologists should be
      aware that cisatracurium has the potential to trigger severe anaphylactic
      reactions via an immune-mediated mechanism. 

PMID- 24023999
TI  - Anesthetic management including extracorporeal membrane oxygenation therapy of
      liver transplant recipient with life-threatening hypoxemia -a case report-.
AB  - We present a rare case of successful anesthetic management for a patient who had
      refractory hypoxia during liver transplantation (LT) with intraoperative veno
      venous (VV) extracorporeal membrane oxygenation (ECMO) support. A 49 year-old
      female patient underwent living donor LT. After reperfusion of the grafted liver,
      graft congestion and massive oozing developed. Thus it was decided to reoperate
      with a temporary gauze packing. However, the patient's condition deteriorated
      with azotemia and severe hypoxemia. VV ECMO with continuous renal replacement
      therapy was started 24 hours before secondary LT and maintained during secondary
      LT. VV ECMO was weaned 32 hours after secondary LT. This case indicates that not
      only after the LT but also before and during LT, VV ECMO can be a treatment
      option for the patient with end-stage liver disease combined with respiratory
      failure when there is the possibility of lung recovery. 

PMID- 24024000
TI  - Application of cerebral oximetry for a parturient with Takayasu's arteritis
      undergoing cesarean section -a case report-.
AB  - Takayasu's arteritis (TA) is a chronic inflammatory disease involving the aorta.
      Because TA sometimes involves cerebral arteries, anesthetic debates focus on
      cerebral monitoring. There is limited evidence as to which cerebral monitoring
      method is most adequate. Furthermore, there is insufficient evidence to determine
      which anesthetic technique is better for TA parturients. We experienced the case
      of a TA parturient who developed transient cerebral ischemia during cesarean
      section. The patient's TA involved her cerebral arteries, and her regional
      cerebral oxygen saturation (rSO2) was lower in the left side than in the right
      side. She complained of speech impairment, tinnitus, and stiffness of the
      posterior neck when the rSO2 levels dropped. The FloTrac/VigileoTM system did not
      correlate with clinical symptoms, but the cerebral oximeter displayed the low
      oxygen saturation. We recommend the cerebral oximetry for cerebral monitoring in
      TA parturients who undergo cesarean sections, especially in hemodynamically
      unstable patients under regional anesthesia or unconscious patients under general
      anesthesia. 

PMID- 24024001
TI  - Fluid extravasation caused by bladder perforation during bipolar transurethral
      resection using saline solution -a case report-.
AB  - Transurethral resection of the prostate is the gold standard in the operative
      management of benign prostatic hyperplasia. Bipolar transurethral resection of
      the prostate using saline solution is a safe technique and reduces the risk of
      transurethral resection syndrome. This report discusses a rare complication of
      bipolar transurethral resection of the prostate: the extravasation of 0.9% saline
      solution into intraperitoneal and retroperitoneal cavities due to bladder
      perforation, resulting in respiratory difficulties. 

PMID- 24024002
TI  - Treatment of digit ulcers in a patient with Buerger's disease by using cervical
      spinal cord stimulation -a case report-.
AB  - Buerger's disease (thromboangiitis obliterans) is known as a segmental
      inflammatory vasculitis that involves the small-sized and medium-sized arteries,
      veins, and nerves. Most effective treatment for Buerger's disease is smoking
      cessation. Except for the cessation of tobacco use, surgical revascularization is
      available in severe ischemia and a distal target vessel. Amputation has been used
      as the last treatment option of the disease up to the present. Increasing limb
      survival and decreasing amputation rate is important. This case describes the use
      of spinal cord stimulation (SCS) in patient with Buerger's disease and its effect
      is not only the complete healing of ulcers but also amputation is not performed. 

PMID- 24024003
TI  - Iatrogenic aortic insufficiency following concomitant septal myectomy and aortic
      valve replacement.

PMID- 24024004
TI  - Anesthesia under cardiopulmonary bypass for video assisted thoracoscopic wedge
      resection in patient with spontaneous pneumothorax and contralateral post
      tuberculosis destroyed lung.

PMID- 24024005
TI  - Green discoloration of urine after propofol infusion.

PMID- 24024006
TI  - A comparison of epidural infusion of 0.2, 0.25, and 0.3% ropivacaine with
      fentanyl after unilateral total knee arthroplasty.

PMID- 24024007
TI  - The effectiveness of L2 nerve root block for the management of patients who are
      suffering from chronic low back and referred pain.

PMID- 24024008
TI  - Possible statistical problems of the original paper titled "Predictors of
      difficult intubation": a bad start.

PMID- 24024009
TI  - Rheumatoid Arthritis: Early diagnosis and treatment outcomes.
AB  - Rheumatoid arthritis (RA) is an inflammatory progressive disease which in the
      absence of appropriate treatment can lead to joint destruction and disability.
      Prognosis of RA may be predicted based on the presence of some clinical and
      laboratory evidences. New criteria for classification of RA provide opportunity
      for earlier treatment. Initiation of treatment particularly by combination of
      DMARDs concurrent with short duration of corticosteroid is expected to prevent
      progressive course and even change the natural course of RA. At present any
      patients with clinical synovitis in at least one joint may have definite RA,
      requiring agressive treatment. 

PMID- 24024010
TI  - Risk factors of thyroid cancer in Babol, Northern Iran.
AB  - Background : Thyroid cancer is the most common endocrine malignancy. Several risk
      factors were found to play a role in thyroid cancer. The purpose of the study was
      to determine the risk factors for thyroid cancer, in Babol, north of Iran.
      METHOD: Eighty patients with thyroid cancer were selected as case group and 160
      people living in the neighborhood of the patients as control group. Risk factors
      in both groups were collected and compared. The odds ratio (OR) as well as the
      marginal logistic regression model were used to estimate the possible risk
      factors. Result : X-ray exposure, radioactive exposure, family history of thyroid
      cancer, history of hyperthyroidism, hypothyroidism and thyroid resection were
      found to be the risk factors of thyroid cancer (p<0.05). Passion exposure, OCP
      user, history of hysterectomy, history of thyroid nodule were not correlated to
      thyroid cancer (p>0.05). CONCLUSION: History of goiter or other benign thyroid
      diseases are among the thyroid cancer risk factors in some community-based
      interventions to prevent or treat the disease in early stages are recommended in
      our region.

PMID- 24024011
TI  - Transcranial doppler sonography diagnostic value for the cerebral flow velocity
      changes in the interictal phase of classic migraine.
AB  - BACKGROUND: An imbalance of the cerebrovascular response during functional
      activation of the brain has been postulated as a factor in the pathophysiology of
      migraine. The purpose of this study was to determine the transcranial doppler
      sonography (TDS) diagnostic value for the cerebral flow velocity changes in the
      interictal phase of classic migraine. METHODS: This study was carried out on 46
      patients (23 cases and 23 controls). We used Doppler instrument via trans
      temporal window and detected middle cerebral artery, anterior cerebral artery and
      posterior cerebral artery by 2 MHz probe. The flow velocity in the posterior
      cerebral artery before, during and immediately after stimulation was recorded.
      Stimulation was done using a flickering light in 100 seconds. RESULTS: At the
      baseline, the middle cerebral artery had more peak systolic velocity in
      migraineurs than the control group. Although peak systolic velocity changes in
      the mid-photic period is not statistically significant. On the other hand, post
      photic peak systolic velocity increased significantly. The diagnostic accuracy of
      the peak systolic volume (PSV) changes in the posterior cerebral artery (PCA) for
      the migraine was 72.3%. CONCLUSION: This stimulation we found altered cerebral
      vasomotor reactivity in the interictal phase in migraineurs with visual aura.
      This seemed to be an unavoidable hindrance for the wider implementation of
      functional TCD in diagnostic work up of migraine patients.

PMID- 24024012
TI  - Quality of life during hemodialysis and study dialysis treatment in patients
      referred to teaching hospitals in Urmia-Iran in 2007.
AB  - BACKGROUND: Quality of life (QOL) assessment in patients on chronic Hemodialysis
      (HD) or peritoneal dialysis (PD) has rarely been carried out. The aim of this
      study was to assess the quality of life during hemodialysis and peritoneal
      dialysis treatment in patients referred to teaching hospitals in Urmia, Iran.
      METHODS: All chronic HD and PD patients in Taleghani and Imam Khomeini Teaching
      Hospitals in Urmia were requested to fill in the validated with a health-related
      quality-of-life SF36 questionnaire for assessing health status in five dimensions
      and on a visual analogue scale, allowing computation of a predicted QOL value to
      be compared. RESULTS: Of the 558 questionnaires distributed to chronic HD
      patients, 455 were returned (response rate 82%). Fifty out of 64 PD patients
      (78%) returned the questionnaires. The two groups were similar in age, gender and
      duration of dialysis treatment. Mean QOL was rated at 60+/-18 for HD and 61+/-19
      for PD, for a mean predicted QOL value of 62+/-30 and 58+/-32(,) respectively.
      RESULTS of the five dimensions were similar in both groups, except for a greater
      restriction in usual activities for PD patients (p= 0.007). The highest scores
      were recorded for self-care, with 71% HD and 74% PD patients reporting no
      limitation, and the lowest scores for usual activities, with 14% HD and 23% PD
      patients reporting severe limitation. Experiencing pain/discomfort (for HD and
      PD) or anxiety/depression (for PD) had the highest impact on QOL. CONCLUSION: The
      results show that QOL on PD was better, but such studies have not been performed
      in various areas in Iran and the results may be different because of the
      involvement of many factors such as geographical, socioeconomic and cultural
      items. More studies are required to verify the value of the SF36 measurements in
      predicting the clinical condition of patients with ESRD and their outcomes.

PMID- 24024013
TI  - Thyroid function in major thalassemia patients: Is it related to height and
      chelation therapy?
AB  - BACKGROUND: One of the most common endocrine problems in major beta-thalassemia
      is hypothyroidism (HT). The aim of this study was to evaluate thyroid function
      status in major beta-thalassemia patients older than 10 years old. METHODS: This
      cross sectional study was carried out on thalassemia major patients registered on
      Thalassemia Center of Amirkola Children Hospital in Babol. A questionnaire was
      filled out by the patients to evaluate the demographic information, quality of
      their last transfusions and chelation therapy. Growth parameters were evaluated.
      We assessed serum T4, TSH, T3RU and FTI in all patients and those with
      hypothyroidism, anti-thyroglobulin and anti-thyroid proxidase antibodies were
      checked Results: One hundred-thirty patients (56 males and 74 females) were
      enrolled in this study. The mean age was 20.95+/-7.8 years. Short stature was
      seen in 41(31.3%) patients. In 53(40.8%) patients, weight was under normal range.
      HT was found in 19 patients (14.6%); 2 primary overt HT, 3 secondary HT and 14
      subclinical HT were detected. No patient with HT had significant serum level of
      anti-thyroid antibodies. Correlation between HT and serum ferritin level was not
      significant (p=0.584) but it was significant for HT and short statures (p=0.002),
      also regular transfusion and chelation therapy were correlated with ferritin
      level. CONCLUSION: High prevalence of HT among thalassemic patients signifies the
      importance of regular screening for evaluation of endocrine function in these
      patients; especially when short stature is present.

PMID- 24024014
TI  - High maternal hemoglobin concentration in first trimester as risk factor for
      pregnancy induced hypertension.
AB  - BACKGROUND: High maternal hemoglobin (Hb) concentration was considered a risk
      factor for the developing of pregnancy hypertension. The purpose of this study
      was to determine whether high maternal Hb concentration in first trimesters
      associated with pregnancy induced hypertension in Iranian nulliparous women.
      METHODS: This study was carried out in teaching hospital in Sari, Iran. Samples
      were obtained from 1008 women who were almost on their 14(th) week pregnancy and
      were admitted to prenatal clinic of this hospital from October 2008 to December
      2009. Their blood pressure was normal. After measuring Hb at first visit, they
      were divided into groups (11<=Hb<13.2 and Hb>=13.2). Pregnancy induced
      hypertension in these groups were compared. RESULTS: In normal Hb group,
      14(2.75%) women had hypertension and in high Hb group, 21(4.2%) had hypertension
      (p=0.045). High hemoglobin concentration in the first trimester showed a risk
      factor for pregnancy induced hypertension (OR= 2.462; 95% CI, 1-6.9). CONCLUSION:
      The results showed that women with high hemoglobin concentration in the first
      trimester carried an increased risk of pregnancy induced hypertension.

PMID- 24024015
TI  - Mycobacterium marinum as a cause of skin chronic granulomatous in the hand.
AB  - BACKGROUND: Mycobacterium marinum infection has a worldwide distribution and the
      organism occupies many aquatic environments. Infections in human consist of
      nodular cutaneous lesions that can progress to tenosynovitis, arthritis, and
      osteomyelitis. Case presentation : A 27-year-old man was presented with a history
      of swelling and exudative erythematous lesions and pustules of the right forearm.
      He worked as a laborer at an aquarium store. A smear from the walls of the
      necrotic center when stained for acid-fast bacilli revealed organisms consistent
      with mycobacteria. CONCLUSION: Cutaneous nodular lesion on the hand or forearm of
      the patient working in aquatic environment, M marinum should be considered in the
      differential diagnosis.

PMID- 24024016
TI  - Spontaneous regression of one nonfunctioning pituitary macroadenoma associated
      with abnormal liver enzyme tests.
AB  - Background : Nowadays, drug and observation are advised to patients with
      lymphocytic hypophysitis and in some cases with nonfunctioning pituitary
      macoadenoma, instead of surgery. CASE PRESENTATION: In this article, we report a
      woman with nonfunctional pituitary macroadenoma and panhypopitutarism and
      negative criteria for lymphocytic hypophysitis associated with increased liver
      enzymes. After three months adenoma rapidly regressed and liver function tests
      were normal without any treatment. Conclusion : Seemingly, viral infection as one
      of the factors may be considered in cases with spontaneous regressed pituitary
      nonfunctional adenoma.

PMID- 24024017
TI  - Knee osteoarthritis prevalence, risk factors, pathogenesis and features: Part I.
AB  - Osteoarthritis (OA) a common disease of aged population and one of the leading
      causes of disability. Incidence of knee OA is rising by increasing average age of
      general population. Age, weight, trauma to joint due to repetiting movements in
      particular squatting and kneeling are common risk factors of knee OA. Several
      factors including cytokines, leptin, and mechanical forces are pathogenic factors
      of knee OA. In patients with knee pain attribution of pain to knee OA should be
      considered with caution. Since a proportion of knee OA are asymptomatic and in a
      number of patients identification of knee OA is not possible due to low
      sensitivity of radiographic examination. In this review data presented in regard
      to prevalence, pathogenesis, risk factors. 

PMID- 24024018
TI  - Metabolic capacity of CYP2D6 within an Iranian population (Mazandaran Province).
AB  - BACKGROUND: CYP2D6 is polymorphically expressed enzyme that show marked
      interindividual and interethnic variation. Phenotyping of CYP2D6 provides
      valuable information about real-time activity of this important drug-metabolizing
      enzymes through the use of specific probe drugs. The aim of this study was to
      identify the CYP2D6 oxidation phenotype with dextromethorphan (DEX) as a probe
      drug in Mazandarani ethnic group among Iranian population. METHODS: The study
      included 71 unrelated healthy volunteers. Dextromethorphan hydrobromide (30 mg)
      was given orally to healthy subjects and peripheral venous blood samples (10 ml)
      were taken at 3 hr post-dose. Dextromethorphan and the metabolite dextrorphan
      (DOR) were analyzed by the HPLC method. The log DEX/DOR metabolic ratio (MR) at 3
      hr plasma sample was used as the index of CYP2D6 activity and a value of 0.3 was
      used as the antimode separating extensive metabolizers (EM) and poor metabolizers
      (PM) phenotypes. RESULTS: A 560-fold interindividual variation in
      dextromethorphan MRs was observed in this study. Considering the antimode 0.3 in
      log scale, 7.04% (5/71) volunteers were identified as PMs. Conclusion : The
      result showed that the frequency of CYP2D6 PM phenotypes accounted for 7.04% of
      subjects in our samples. Despite these findings, we propose a further study in
      larger samples to provide a wider image and to get more valuable information upon
      pharmacogenetic basis for individual therapy and personalized medicine.

PMID- 24024019
TI  - Comparative study of levamisole-selenium supplementation effect on CD4 increase
      in HlV / AIDS patients.
AB  - BACKGROUND: Given to the abundant incidence of malnutrition in HIV(+) patients
      and its effect on progress of AIDS disease, several studies have recommended
      supplementation therapy (such as Selenium, Levamisole, Zinc). METHODS: This
      clinical trial was prefunded on patient's with HIV + in Behavior Diseases
      Consulting Center, Kermanshah, Iran 2006-2007. One hundred-seventy eight out of
      all patients with CD4 1ess than 350 cell/mm(3) who did not receive antiretroviral
      drugs were in this study. They were divided into four groups: the first group
      received 200 micg selenium per day, the second group received levamisole 50 mg
      every other day, and third group received both two drugs. The fourth group was
      the control group. All four groups were studied for six months. Patients'
      baseline CD4 and other data were recorded in a form. CD4 was rechecked after six
      months and collected values were compared with basic values. CD4 changes were
      compared among all groups, either. RESULTS: One hundred-seventy eight patients
      initiated treatment and 108 cooperated in the 6-month follow up assessment.
      Niuety-two (85%) were males and 15% were female. CD4 decreased in control group
      and Levamisole group during the study which was significant, but 13 units
      increase was seen in Selenium-Levamisole group. CD4 count decreased 36 units in
      Selenium group. Comparing CD4 count change among 4 study groups showed that only
      CD4 change between Selenium-Levamisole group and control group was significant.
      CONCLUSION: Regarding to collected results, Selenium-Levamisole supplementation
      can be used as a supplementation therapy besides antiretroviral therapies.

PMID- 24024020
TI  - The relationship between helicobacter pylori infection and myocardial infarction.
AB  - BACKGROUND: Coronary Artery Disease is known as the main cause of death in
      industrialized countries. Relation between this disease and some infections such
      as Helicobacter pylori (H.pylori) has been shown in several studies. The purpose
      of this study was to dermine the relationship between Hypylori and mycardical
      infarctions. METHODS: Seventy-three myocardial infarction patients and 78
      individuals with no history of this disease were compared. Patients and control
      matched for age and sex person to person by the match method. Levels of serum IgA
      and IgG antibodies against H. pylori were measured by Elisa method. Also,
      cholesterol, triglyceride, LDL, HDL measured in both groups and data were
      compared between two groups in terms of relation with cardiac risk factors.
      RESULTS: From 151 participants, 73 were patients and 78 were control subjects.
      The percentage of IgG positive cases against H. pylori was 57.5% in the case
      group and 32.1% in the control group (p=0.002, OR: 2.87 CI: 95%; 1.5-5.6).
      Meanwhile, there was no significant difference in IgA positive cases between the
      two groups (42.5% and 48.7% in the case and control groups, respectively)
      (p=0.44; OR: 0.78 95% CI; 0.41-1.48). The study showed 74.2% of cases in the case
      group and 45.2% in the control group were positive for both IgG and IgA (p=0.01;
      OR: 3.5 95% CI; 1.3-9.5). No significant differences were found between two
      groups in terms of relation between H. pylori related antibodies level and heart
      disease classic risk factors (smoking, hypertension,...), sex, and age, but
      between dyslipidemia and H. pylori related antibodies was significant differences
      in case group (p=0.05). CONCLUSION: According to the results, it seems there is a
      relation between H. pylori infection and myocardial infarction. Also, between
      dislipidemia and H. Pylori antibodies in case group were significant difference.
      Therefore, H. pylori can be a new risk factor for atherosclerosis or can be
      exacerbate effect of other risk factors. Proper diagnosis and treatment of these
      infections can be useful in prone patients. More studies with larger sample
      groups are needed to review the possible role of this pathogen as a heart disease
      risk factor.

PMID- 24024021
TI  - Serum interleukins 6 and 8 in mild and severe asthmatic patients, is it
      difference?
AB  - BACKGROUND: About 5-10% of patients with asthma suffer from poorly-controlled
      disease despite corticosteroid (CS) therapy. METHODS: 21 severe and 30 mild
      asthma patients were recruited and underwent collection of blood sample. We
      determined whether there were any differences in inflammatory biomarkers between
      severe and mild asthma patients or not. RESULTS: Levels of Interleukin-8 (IL-8)
      and Interleukin-6 (IL-6) in blood supernatants were similar in both groups of
      asthma patients. Leukocytes were in range of normal in all patients. Increased
      eosinophil was in 29% of severe cases and 23% in mild cases. IgE level was
      increased in 43% of severe form and 50% in mild form. CONCLUSION: There is not
      any difference between severe and mild asthma in serum IL-8 and IL-6. Therefore,
      level of serum cytokines may not predict severity of asthma.

PMID- 24024022
TI  - Hyperprolactinemia in association with subclinical hypothyroidism.
AB  - BACKGROUND: Hyperprolactinemia is the most common endocrine disorder in
      hypothalamic-pituitary axis and has been reported in variable levels in patients
      with overt primary hypothyroidism. We decided to determine the prevalence of
      hyperprolactinemia and clinical related symptoms in subclinical hypothyroidism
      patients. METHODS: In this cross sectional study, prolactin levels of 481
      subclinical hypothyroid patients were assessed. Prolactin measurement was
      performed using chemiluminescent immunoassay. Data were collected and analyzed.
      RESULTS: Sixty-two (13%) patients were males and 419 (87%) were females. The mean
      age of the patients was 32.53+/-10.13 years. Ninty-eight patients (91 females 7
      males) had high prolactin. Prevalence of hyperprolactinemia in subclinical
      hypothyroidism was 20.4%. (11% in men and 22% in women, p=0.05). There was no
      correlation between the serum TSH and prolactin level. Clinical symptom
      prevalence was not different between patients with and without
      hyperprolactinemia. CONCLUSION: This study showed that prevalence of
      hyperprolactinemia in subclinical hypothyroidism is notable and this disorder is
      more common in female subclinical hypothyroidism than the men.

PMID- 24024023
TI  - A periodontal health assessment of hospitalized patients with myocardial
      infarction.
AB  - BACKGROUND: Recent researches have known long term infections such as periodontal
      disease to be related with the process of atherosclerosis. Periodontitis causes
      peripheral inflammation and immune cell stimulation which leads to an increase in
      C - reactive protein (CRP) and IgA Ab and there is a definite relation between
      cardiovascular disease, CRP increase and Periodontitis. The aim of this study was
      to evaluate the periodontal health status of patients with myocardial infarction
      who were hospitalized in Babol and Sari Hospitals. METHODS: This descriptive
      study was done on 95 men and women age ranging from 40 to 70 years old
      hospitalized due to myocardial infarction diagnosis in Babol and Sari Hospitals.
      Periodontal health, of patients evaluated via Cowell Bleeding Index, Green and
      vermillion Debri Index, Tooth Mobility, Clinical attachment Level on Ramfjord
      teeth. Data were analyzed with SPSS and Kruskal-Wallis test and Mann-whitney
      test. RESULTS: Considered indexes were evaluated in 81men and 14 women studied
      which showed no significant difference among them in the average BI (p=0.52),
      average tooth mobility (p=0.117) and average CAL index (p=0.745). The only
      significant difference between men and women was found in average DI index
      (p=0.08). There was a significant difference between average CAL in Ramfjord
      teeth of upper and lower jaw (p=0.002). CONCLUSION: According to high prevalence
      of periodontitis in our study, periodontitis may be a risk factor of
      cardiovascular disease, it should be pointed out that here is the cardiologists'
      emphasis on their patients referring to the dentists.

PMID- 24024024
TI  - Prevalence burn injuries and risk factors in persons older the 15 years in Urmia
      burn center in Iran.
AB  - BACKGROUND: Burn injuries in many respects is the most tragic that a person may
      experience. The purpose of this study was to know the burn casualties prevalence
      in people over 15 years old to identify the risk and predisposing factors in the
      province of west Azarbaijan of Iran. METHODS: This cross-sectional study was
      performed from March 2008 to March 2010. The demographic and epidemiologic
      information about burn and its complications were extracted from the data banks
      and records. Data were collected and analyzed. RESULTS: Four hundred twenty eight
      patients (44.9% female and 56.1% male) were studied. Most of the admissions were
      in 16 to 25 years age bracket. Burning with fire accounted (39.2%) of admission
      in males and (53.2%) in females which was the most common cause of burning.
      Percentage patients who had more than 40% body surface area (BSA) burned was
      42.0% in males, and 30.1% in females. Patients with >40% BSA burn had a mortality
      of 73.8%. The mean body surface area burned was 33.8% in males and 25.2% in
      females. The mean duration of hospitalization was 6.19 days. CONCLUSION: The
      results of this study show that the prevalence of burn injuries is relatively
      high with high mortality rate in those with BSA> 40%. The commonest cause of burn
      was fire.

PMID- 24024025
TI  - Severe generalized muscular atrophia, nerve optic atrophia, ear problem and
      disability with Pelger-Huet anomaly.
AB  - BACKGROUND: The Pelger-Huet anomaly dominantly is a rare and benign inherited
      defect of terminal neutrophil differentiation. Although neutrophil migration may
      be minimally impaired, granulocytes function is otherwise normal association
      abnormalities such as ocular, musculoskeletal are reported very rare. Case
      Presentation : An eight year-old boy with good consciousness but severe muscular
      atrophia and difficulty in respiration was admitted in Amirkola Hospital at Babol
      University of Medical Sciences Babol, Iran. The patient was febrile at
      presentation. The chest x-ray was normal and other causes of respiratory problem
      were ruled out. The patient and his mother have 30% to 40% band and Pelger-Huet
      cells in peripheral blood smear. He gradually has gotten hearing loss and
      decreased visual acuity for three years. He has optic nerve atrophia. CONCLUSION:
      The patient is an unusual type of Pelger-Huet anomaly with multiple organ
      dysfunctions probably due to simultaneous muscular degenerative disease.

PMID- 24024027
TI  - Manifestations of adipose tissue dysfunction.

PMID- 24024026
TI  - Obesity in american Indian and mexican american men and women: associations with
      blood pressure and cardiovascular autonomic control.
AB  - Obesity is a serious public health problem, especially in some minority
      communities, and it has been associated with an increased risk of cardiovascular
      diseases. While obesity is a serious health concern in both American Indian and
      Mexican American populations, the relationship between obesity and cardiac
      autonomic control in these two populations is not well understood. The present
      study in a selected sample of American Indians and Mexican Americans assessed
      associations between obesity, blood pressure (BP), and cardiovascular autonomic
      control. Cardiovascular autonomic control, systolic and diastolic mean BP, and
      body mass index were obtained from one hundred thirty-two American Indian and
      Mexican American men and women who are literate in English and are residing
      legally in San Diego County. Men had a significant greater systolic and diastolic
      BP and were more likely to develop systolic prehypertension and hypertension than
      women. Obese participants showed greater mean heart rate (HR) and systolic and
      diastolic BP than nonobese participants. Obese men also exhibited greater cardiac
      sympathetic activity and lower cardiovagal control than obese women. These
      results suggest that obesity and gender differences in cardiovascular autonomic
      control may contribute to risk for cardiovascular disorders in this sample of
      American Indians and Mexican Americans. 

PMID- 24024028
TI  - Electroencephalogram of age-dependent epileptic encephalopathies in infancy and
      early childhood.
AB  - Epileptic encephalopathy syndromes are disorders in which the epileptiform
      abnormalities are thought to contribute to a progressive cerebral dysfunction.
      Characteristic electroencephalogram findings have an important diagnostic value
      in classification of epileptic encephalopathy syndromes. In this paper, we focus
      on electroencephalogram findings of childhood epileptic encephalopathy syndromes
      and provide sample illustrations. 

PMID- 24024029
TI  - Improvement research priorities: USA survey and expert consensus.
AB  - The purpose of this study was to identify stakeholder views about national
      priorities for improvement science and build agreement for action in a national
      improvement and implementation research network in the USA. This was accomplished
      using three stages of identification and consensus. (1) Topics were identified
      through a multipronged environmental scan of the literature and initiatives. (2)
      Based on this scan, a survey was developed, and stakeholders (n = 2,777) were
      invited to rate the resulting 33-topic, 9-category list, via an online survey.
      Data from 560 respondents (20% response) were analyzed. (3) An expert panel used
      survey results to further refine the research priorities through a Rand Delphi
      process. Priorities identified were within four categories: care coordination and
      transitions, high-performing clinical systems and microsystems improvement
      approaches, implementation of evidence-based improvements and best practices, and
      culture of quality and safety. The priorities identified were adopted by the
      improvement science research network as the research agenda to guide strategy.
      The process and conclusions may be of value to quality improvement research
      funding agencies, governments, and research units seeking to concentrate their
      resources on improvement topics where research is capable of yielding timely and
      actionable answers as well as contributing to the knowledge base for improvement.

PMID- 24024030
TI  - "Values that vanish into thin air": nurses' experience of ethical values in their
      daily work.
AB  - The objective of this study was to examine how nurses experience ethical values
      as they are expressed in daily practice in a Norwegian hospital. A growing focus
      in Western healthcare on effectiveness, production, and retrenchment has an
      influence on professional nursing standards and nursing values. Lack of resources
      and subsequent ethically difficult prioritizations imply a strain on nurses. This
      study is qualitative. Data collection was carried out by conducting 4 focus group
      interviews. The data was analyzed using content analysis. The results are
      presented in two main themes: (1) values and reflection are important for the
      nurses; (2) time pressure and nursing frustrations in daily work. The results
      demonstrate that nurses believe the ethical values to be of crucial importance
      for the quality of nursing; however, the ethical values are often repressed in
      daily practice. This results in feeling of frustration, fatigue, and guilty
      conscience for the nurses. There is a need for changes in the system which could
      contribute to the development of a caring culture that would take care of both
      patients and nurses. In an endeavour to reach this goal, one could apply
      caritative leadership theory, which is grounded on the caritas motive, human
      love, and mercy. 

PMID- 24024031
TI  - Does the RIFLE Classification Improve Prognostic Value of the APACHE II Score in
      Critically Ill Patients?
AB  - Introduction. The RIFLE classification defines three severity criteria for acute
      kidney injury (AKI): risk, injury, and failure. It was associated with mortality
      according to the gradation of AKI severity. However, it is not known if the
      APACHE II score, associated with the RIFLE classification, results in greater
      discriminatory power in relation to mortality in critical patients. Objective. To
      analyze whether the RIFLE classification adds value to the performance of APACHE
      II in predicting mortality in critically ill patients. Methods. An observational
      prospective cohort of 200 patients admitted to the ICU from July 2010 to July
      2011. Results. The age of the sample was 66 (+/-16.7) years, 53.3% female. ICU
      mortality was 23.5%. The severity of AKI presented higher risk of death: class
      risk (RR = 1.89 CI:0.97-3.38, P = 0.001), grade injury (RR = 3.7 CI:1.71-8.08, P
      = 0.001), and class failure (RR = 4.79 CI:2.10-10.6, P = 0.001). The APACHE II
      had C-statistics of 0.75, 95% (CI:0.68-0.80, P = 0.001) and 0.80 (95% CI:0.74 to
      0.86, P = 0.001) after being incorporated into the RIFLE classification in
      relation to prediction of death. In the comparison between AUROCs, P = 0.03.
      Conclusion. The severity of AKI, defined by the RIFLE classification, was a risk
      marker for mortality in critically ill patients, and improved the performance of
      APACHE II in predicting the mortality in this population. 

PMID- 24024032
TI  - Feasibility of remote real-time guidance of a cardiac examination performed by
      novices using a pocket-sized ultrasound device.
AB  - Background. The potential of pocket-sized ultrasound devices (PUDs) to improve
      global healthcare delivery is limited by the lack of a suitable imaging protocol
      and trained users. Therefore, we investigated the feasibility of performing a
      brief, evidence-based cardiac limited ultrasound exam (CLUE) through wireless
      guidance of novice users. Methods. Three trainees applied PUDs on 27 subjects
      while directed by an off-site cardiologist to obtain a CLUE to screen for LV
      systolic dysfunction (LVSD), LA enlargement (LAE), ultrasound lung comets (ULC+),
      and elevated CVP (eCVP). Real-time remote audiovisual guidance and interpretation
      by the cardiologist were performed using the iPhone 4/iPod (FaceTime, Apple,
      Inc.) attached to the PUD and transmitted data wirelessly. Accuracy and technical
      quality of transmitted images were compared to on-site, gold-standard echo
      thresholds. Results. Novice versus sonographer imaging yielded technically
      adequate views in 122/135 (90%) versus 130/135 (96%) (P < 0.05). CLUE's combined
      SN, SP, and ACC were 0.67, 0.96, and 0.90. Technical adequacy (%) and accuracy
      for each abnormality (n) were LVSD (85%, 0.93, n = 5), LAE (89%, 0.74, n = 16),
      ULC+ (100%, 0.94, n = 5), and eCVP (78%, 0.91, n = 1). Conclusion. A novice can
      perform the CLUE using PUD when wirelessly guided by an expert. This method could
      facilitate PUD use for off-site bedside medical decision making and triaging of
      patients. 

PMID- 24024033
TI  - Does the Inclusion of Virtual Reality Games within Conventional Rehabilitation
      Enhance Balance Retraining after a Recent Episode of Stroke?
AB  - This randomised controlled and double-blinded pilot study evaluated if
      interactive virtual reality balance related games integrated within conventional
      rehabilitation sessions resulted in more superior retraining of dynamic balance
      compared to CR after stroke. 19 subjects diagnosed with a recent episode of
      stroke were recruited from a local rehabilitation hospital and randomly assigned
      to either a control or an experimental group. Subjects in the control groups
      underwent 60 minutes of conventional rehabilitation while those in the
      experimental groups underwent 40 minutes of convention rehabilitation and 20
      minutes of self-directed virtual reality balanced rehabilitation. Functional
      Reach Test, Timed Up and Go, Modified Barthel Index, Berg Balance Scale, and
      Centre of Pressure of subjects in both groups were evaluated before and on
      completion of the rehabilitation sessions. Results indicate that the inclusion of
      interactive virtual reality balance related games within conventional
      rehabilitation can lead to improved functional mobility and balance after a
      recent episode of stroke without increasing treatment time that requires more
      health professional manpower. 

PMID- 24024034
TI  - Development of oral sustained release rifampicin loaded chitosan nanoparticles by
      design of experiment.
AB  - Objective. The main objective of the present investigation was to develop and
      optimize oral sustained release Chitosan nanoparticles (CNs) of rifampicin by
      design of experiment (DOE). Methodology. CNs were prepared by modified emulsion
      ionic gelation technique. Here, inclusion of hydrophobic drug moiety in the
      hydrophilic matrix of polymer is applied for rifampicin delivery using CN. The
      2(3) full-factorial design was employed by selecting the independent variables
      such as Chitosan concentration (X 1), concentration of tripolyphosphate (X 2),
      and homogenization speed (X 3) in order to achieve desired particle size with
      maximum percent entrapment efficiency and drug loading. The design was validated
      by checkpoint analysis, and formulation was optimized using the desirability
      function. Results. Particle size, drug entrapment efficiency, and drug loading
      for the optimized batch were found to be 221.9 nm, 44.17 +/- 1.98% W/W, and 42.96
      +/- 2.91% W/W, respectively. In vitro release data of optimized formulation
      showed an initial burst followed by slow sustained drug release. Kinetic drug
      release from CNs was best fitted to Higuchi model. Conclusion. Design of
      Experiment is an important tool for obtaining desired characteristics of
      rifampicin loaded CNs. In vitro study suggests that oral sustained release CNs
      might be an effective drug delivery system for tuberculosis. 

PMID- 24024035
TI  - Etiologies and outcomes of acute liver failure in a spanish community.
AB  - Previous retrospective study (1992 to 2000) performed in Spain showed that drug
      toxicity, viral hepatitis, and indeterminate etiology were the most prevalent
      causes of acute liver failure (ALF). In the last decade, there is no information
      about ALF in our country. For these reasons we analyze retrospectively, in a ten
      year period (2000 to 2010), the presumed causes, clinical characteristics,
      course, and outcome of ALF in a Spanish community. Causes of ALF were
      indeterminate in 4 patients (24%), acute hepatitis B infection in 4 patients
      (24%), drug or toxic reactions in 4 patients (24%), including one case of
      acetaminophen overdose, followed by miscellaneous causes. The overall short-term
      survival (6 weeks after admission) was 65%. Liver transplantation was performed
      in 11 patients with a survival of 82%. Despite fulfilling criteria, 2 patients
      were not transplanted because of contraindications; they both died. In summary,
      acute hepatitis B and indeterminate cause are still being the most frequent
      causes of ALF in our region, and patients with ALF have an excellent chance of
      survival after emergency liver transplantation. Acetaminophen overdose still
      represents a very rare cause of ALF in our community. 

PMID- 24024036
TI  - Long-term fluoride exchanges at restoration surfaces and effects on surface
      mechanical properties.
AB  - Aim. The aim of the study was to determine whether three fluoride containing
      resin composites could maintain fluoride release, fluoride recharge, and
      mechanical stability over long-term (18-month) aging. Materials and Methods.
      Fluoride containing composites Beautifil II, Gradia Direct X, Tetric EvoCeram,
      and glass ionomer Fuji IX Extra were analyzed. Specimens of each material were
      fabricated for two test groups: Group 1: bimonthly fluoride release/recharge
      analysis (n = 5); Group 2: hardness and elastic modulus analysis (n = 6).
      Nanoindentation was employed at 24 hours and at 1, 3, 6, 12, and 18 months. After
      18 months, each specimen was immersed (recharged) in 5000 ppm NaF gel, and
      fluoride rerelease, hardness, and elastic modulus were measured. Results.
      Beautifil II and Gradia Direct X maintained fluoride release and recharge
      capability throughout 18-month aging (Beautifil II > Gradia Direct X > Tetric
      EvoCeram). The fluoride rerelease from Beautifil II following a 10-minute NaF
      recharge (at 18 months) was comparable to the long-term fluoride release from
      Fuji IX Extra. Elastic modulus and hardness did not change significantly (P >
      0.05) with fluoride release, recharge, and water aging over 18 months for all
      three analyzed composites. Conclusions. The long-term fluoride release, fluoride
      recharge, and mechanical property stability of Beautifil II and Gradia Direct X
      render these composites suitable for load bearing restorations in high caries
      risk patients. Clinical Relevance. The ability for Beautifil II and Gradia Direct
      X to maintain fluoride release and fluoride recharge capability, despite long
      term aging, raises the potential for unrestored tooth surfaces in contact with
      Beautifil II or Gradia Direct X restorations to demonstrate a reduced rate of
      caries incidence compared to unrestored surfaces adjacent to conventional
      nonfluoride containing composites. 

PMID- 24024037
TI  - Comparison of in vitro and in situ methods for studying lipolysis.
AB  - Lipolysis is a highly regulated process and is controlled by nervous system,
      hormones, and paracrine/autocrine factors. Dysregulation of lipolysis is
      associated with some pathophysiological conditions including diabetes, metabolic
      syndrome, and obesity. Nowadays, special attention isthereforepaid to study
      lipolysis using different experimental models. This review summarizes the current
      experimental methods for studying lipolysis. Culture of preadipocyte cell lines,
      use of differentiated stroma-vascular cells, primary culture of adipocyte, organ
      culture of adipose tissue, and microdialysis technique are the most widely used
      techniques to study lipolysis. The advantages and limitations of using these
      methods are discussed. 

PMID- 24024038
TI  - Natal and neonatal teeth: an overview of the literature.
AB  - The occurrence of natal and neonatal teeth is an uncommon anomaly, which for
      centuries has been associated with diverse superstitions among different ethnic
      groups. Natal teeth are more frequent than neonatal teeth, with the ratio being
      approximately 3 : 1. It must be considered that natal and neonatal teeth are
      conditions of fundamental importance not only for a dental surgeon but also for a
      paediatrician since their presence may lead to numerous complications. Early
      detection and treatment of these teeth are recommended because they may induce
      deformity or mutilation of tongue, dehydration, inadequate nutrients intake by
      the infant, and growth retardation, the pattern and time of eruption of teeth and
      its morphology. This paper presents a concise review of the literature about
      neonatal teeth. 

PMID- 24024039
TI  - Antitussive Efficacy and Safety Profile of Ethyl Acetate Fraction of Terminalia
      chebula.
AB  - Antitussive effects of ethyl acetate fraction of Terminalia chebula on sulphur
      dioxide (SO2) gas induced cough have been examined in mice. Safety profile of
      Terminalia chebula was established by determining LD50 and acute neurotoxicity.
      The result showed that extract of Terminalia chebula dose dependently suppressed
      SO2 gas induced cough in mice. Terminalia chebula, after i.p. administration at
      dose level 500 mg/kg, offered maximum cough suppressive effects; that is, number
      of coughs at 60 min was 12 +/- 1.52 (mean +/- SEM) as compared to codeine 10
      mg/kg; i.p., dextromethorphan 10 mg/kg; i.p., and saline, having frequency of
      cough 10.375 +/- 0.866, 12.428 +/- 0.81, and 46 +/- 2.61, respectively. LD50
      value of Terminalia chebula was approximately 1265 mg/kg, respectively. No sign
      of neural impairment was observed at antitussive doses of extract. Antitussive
      effect of Terminalia chebula was partly reversed with treatment by naloxone (3
      mg/kg; s.c.) while rimcazole (3 mg/kg; s.c.) did not antagonize its cough
      suppression activity. This may suggest that opioid receptors partially contribute
      in antitussive action of Terminalia chebula. Along with this, the possibility of
      presence of single or multiple mechanisms activated by several different
      pharmacological actions (mainly anti-inflammatory, antioxidant, spasmolytic,
      antibacterial, and antiphlegmatic) could not be eliminated. 

PMID- 24024040
TI  - The effect of low-level laser therapy on hearing.
AB  - One purported use of low-level laser therapy (LLLT) is to promote healing in
      damaged cells. The effects of LLLT on hearing loss and tinnitus have received
      some study, but results have been equivocal. The purpose of this study was to
      determine if LLLT improved hearing, speech understanding, and/or cochlear
      function in adults with hearing loss. Using a randomized, double-blind, placebo
      controlled design, subjects were assigned to a treatment, placebo, or control
      group. The treatment group was given LLLT, which consisted of shining low-level
      lasers onto the outer ear, head, and neck. Each laser treatment lasted
      approximately five minutes. Three treatments were applied within the course of
      one week. A battery of auditory tests was administered immediately before the
      first treatment and immediately after the third treatment. The battery consisted
      of pure-tone audiometry, the Connected Speech Test, and transient-evoked
      otoacoustic emissions. Data were analyzed by comparing pre- and posttest results.
      No statistically significant differences were found between groups for any of the
      auditory tests. Additionally, no clinically significant differences were found in
      any individual subjects. This trial is registered with ClinicalTrials.gov
      (NCT01820416). 

PMID- 24024043
TI  - A rare case report of amlodipine-induced gingival enlargement and review of its
      pathogenesis.
AB  - Gingival enlargement is a common clinical feature of gingival and periodontal
      diseases. It is an unwanted side effect of certain systemic drugs given for
      nondental treatment. It is being reported with three main groups of drugs like
      calcium channel blockers (CCBs), immunosuppressants, and anticonvulsants. Among
      calcium channel blockers, nifedipine causes gingival hyperplasia in about 10% of
      patients, whereas the incidence of amlodipine-, a third generation calcium
      channel blocker, induced gingival hyperplasia is very limited. There are very few
      reports of amlodipine-induced gingival enlargement at a dose of 5 mg. We report a
      case of amlodipine-induced gingival enlargement in a 45-year-old hypertensive
      patient taking amlodipine at a dose of 5 mg. 

PMID- 24024041
TI  - Activity-dependent NPAS4 expression and the regulation of gene programs
      underlying plasticity in the central nervous system.
AB  - The capability of the brain to change functionally in response to sensory
      experience is most active during early stages of development but it decreases
      later in life when major alterations of neuronal network structures no longer
      take place in response to experience. This view has been recently challenged by
      experimental strategies based on the enhancement of environmental stimulation
      levels, genetic manipulations, and pharmacological treatments, which all have
      demonstrated that the adult brain retains a degree of plasticity that allows for
      a rewiring of neuronal circuitries over the entire life course. A hot spot in the
      field of neuronal plasticity centres on gene programs that underlie plastic
      phenomena in adulthood. Here, I discuss the role of the recently discovered
      neuronal-specific and activity-dependent transcription factor NPAS4 as a critical
      mediator of plasticity in the nervous system. A better understanding of how
      modifications in the connectivity of neuronal networks occur may shed light on
      the treatment of pathological conditions such as brain damage or disease in adult
      life, some of which were once considered untreatable. 

PMID- 24024044
TI  - The Anterior Ratio: The Missing Link between Orthodontics and Aesthetic
      Dentistry.
AB  - There is an increase in the number of dentists using orthodontic treatment for
      anterior tooth alignment. This is either combined with additive bonding or
      interproximal reduction; knowing "when to" and "how much" requires an
      understanding of the anterior ratio. This case report explains how to use the
      anterior ratio to help provide optimal aesthetics and function for the ortho
      restorative patient. The anterior ratio is an important diagnostic tool required
      for both disciplines of orthodontics and restorative dentistry which is often
      overlooked. The case report demonstrates the use of the Invisalign orthodontic
      appliance and the corresponding ClinCheck software to help achieve the proposed
      treatment goals. 

PMID- 24024042
TI  - Microglia and spinal cord synaptic plasticity in persistent pain.
AB  - Microglia are regarded as macrophages in the central nervous system (CNS) and
      play an important role in neuroinflammation in the CNS. Microglial activation has
      been strongly implicated in neurodegeneration in the brain. Increasing evidence
      also suggests an important role of spinal cord microglia in the genesis of
      persistent pain, by releasing the proinflammatory cytokines tumor necrosis factor
      alpha (TNFalpha), Interleukine-1beta (IL-1beta), and brain derived neurotrophic
      factor (BDNF). In this review, we discuss the recent findings illustrating the
      importance of microglial mediators in regulating synaptic plasticity of the
      excitatory and inhibitory pain circuits in the spinal cord, leading to enhanced
      pain states. Insights into microglial-neuronal interactions in the spinal cord
      dorsal horn will not only further our understanding of neural plasticity but may
      also lead to novel therapeutics for chronic pain management.

PMID- 24024045
TI  - Nonsyndromic facial asymmetry with unilateral condylar aplasia.
AB  - Introduction. The temporomandibular joint (TMJ) is the most complex elegantly
      designed joint in the human body. Abnormal development and growth of TMJ may lead
      to condyle aplasia present in several syndromes expressions, but it is extremely
      rare when not connected to any underlying pathological disorder or in conjunction
      with any syndrome. Objective. A rare case of aplasia of the mandibular condyle is
      presented, along with 3D computed tomography (3D CT) findings. Conclusion. Based
      on clinical and radiological findings we suggest the abnormal development of the
      TMJ as the origin. The 3D CT has provided high-quality images, which made
      diagnosis and a prompt treatment plan possible. 

PMID- 24024046
TI  - Two cases of accidental injection of epinephrine into a digit treated with
      subcutaneous phentolamine injections.
AB  - Accidental injection into the digit from an epinephrine autoinjection device can
      cause discoloration, pain, and paresthesias. Although loss of digit is rare,
      treatment in the emergency department is commonly aimed at vasodilation of the
      affected tissue. We report two cases of accidental injection of epinephrine into
      the digits that were successfully treated with subcutaneous phentolamine
      injection with no adverse events. 

PMID- 24024047
TI  - Optic disc swelling and vision loss in a patient with cystic fibrosis and
      diabetes.
AB  - Advances in cystic fibrosis management have significantly improved life
      expectancy in these patients. However, we are now faced with a growing number of
      long-term extrapulmonary consequences of this disease, including ophthalmic
      complications of diabetes in cystic fibrosis patients. We present a unique report
      that documents a case of diabetic papillopathy progressing to nonarteritic
      anterior ischemic optic neuropathy resulting in vision loss in a patient with CF
      and diabetes. It highlights the potentially devastating consequences of
      longstanding diabetes in CF patients. 

PMID- 24024048
TI  - A rare occurrence of primary hepatic leiomyosarcoma associated with epstein barr
      virus infection in an AIDS patient.
AB  - Primary hepatic leiomyosarcoma is exceedingly rare accounting for less than 1% of
      the hepatic tumors. Close to 45 cases have been reported in the English
      literature. Presentation is usually nonspecific and diagnosis is often delayed
      until tumors reach a large size. This leads to a dismal prognosis. The tumors are
      not yet fully understood, hence the standard of care is not well defined.
      Curative resection remains the mainstay of management. Close association of
      Epstein Barr virus (EBV) induced soft tissue sarcomas is proven, especially in
      the presence of immunosuppression encountered in HIV/AIDS patients and in
      posttransplant patients. We herein present a case report of a 54-year-old man
      diagnosed to have HIV/AIDS and EBV infection admitted to our hospital with
      complaints of intractable hiccups for more than a week. Extensive workup revealed
      primary leiomyosarcoma of the liver. 

PMID- 24024049
TI  - Autoimmune hepatitis: diagnostic dilemma in the setting of suspected iron
      overload.
AB  - Autoimmune hepatitis (AIH) is an inflammatory condition of the liver that has a
      multitude of clinical presentations from chronic hepatitis to acute fulminant
      hepatitis. AIH diagnosis is typically suspected after ruling out other causes of
      hepatitis (such as vial hepatitis, hemochromatosis, Wilson's disease, and primary
      biliary cirrhosis) through serological tests and by findings of high titers of
      certain autoantibodies (ANA and anti-SMA for type 1 AIH and anti-LKM-1 for type 2
      AIH). AIH like most inflammatory conditions is associated with increased ferritin
      levels (acute-phase reactant) but typically near-normal transferrin saturation.
      The presence of excessive ferritin level in absence of high-transferrin
      saturation helps differentiate secondary iron overload from hemochromatosis where
      transferrin saturation is typically high. We herein describe a case of AIH that
      presented with high ferritin levels and transferrin saturation suggesting a
      diagnosis of hemochromatosis and needed arduous work-up to arrive at accurate
      diagnosis of AIH. 

PMID- 24024050
TI  - Spontaneous retroperitoneal hemorrhage in a patient with prolymphocytic
      transformation of chronic lymphocytic leukemia.
AB  - Prolymphocytic transformation of chronic lymphocytic leukemia is a rare but
      recognized entity. We present the case of a 76-year-old gentleman with a previous
      diagnosis of chronic lymphocytic leukemia who presented with fatigue, fever, and
      a white blood cell count of 500 000 with prolymphocytes on peripheral blood
      examination. Chlorambucil and dexamethasone were initiated. He developed
      progressive anemia during his admission with no clear cause on initial CT
      examination. Bilateral hip pain began several days later and he was unfortunately
      diagnosed with a large spontaneous retroperitoneal hemorrhage postmortem. This
      condition is rare and generally occurs in those receiving therapeutic
      anticoagulation or dialysis, with known bleeding disorders or vascular
      malformation, none of which were present in our patient. Pathology revealed
      marked leukemoid engorgement of the vessels of many organs with prolymphocytes.
      We discuss the potential etiologies and relationships between these critical
      diagnoses. 

PMID- 24024051
TI  - Bilateral pleural effusion in a patient with an extensive extramedullary
      hematopoietic mass.
AB  - We present a 56-year-old woman with bilateral pleural effusions, widespread
      enlarged lymph nodes, and soft tissue masses located within the renal pelvis. The
      initially working diagnosis was tuberculosis and lymphoma. Further pathological
      examination of the lymph node biopsy confirmed a diagnosis of extramedullary
      hematopoiesis, and a bone marrow biopsy revealed myelofibrosis. Unlike common
      treatment options such as radiotherapy and/or surgery, intrathoracic cisplatin
      and dexamethasone for the treatment of pleural effusions secondary to
      extramedullary hematopoiesis demonstrated an improvement in feasibility and
      efficacy in the present case. 

PMID- 24024052
TI  - Cysticercosis: hooked by a hooklet on fine needle aspiration cytology-a case
      report.
AB  - Cysticercosis is a systemic parasitic disease caused by the larval form of
      cestode T. solium. It has a worldwide distribution and is potentially harmful
      with variable clinical manifestations. The patient most commonly presents with
      subcutaneous and muscle involvement in the form of nodular lesions. The other
      most commonly involved sites include eye, brain, bladder wall, and heart.
      Cysticercosis can be diagnosed on serology, and radiologically but confirmatory
      diagnosis is based on histopathological examination of the involved tissue biopsy
      specimen. Fine needle aspiration cytology is a useful low-cost outpatient
      procedure tool for preoperative diagnosis of cysticercosis and is absolutely
      essential for diagnosis of the parasitic lesions in a peripheral hospital, one
      like ours. 

PMID- 24024053
TI  - Dupuytren's Contracture Cosegregation with Limb-Girdle Muscle Dystrophy.
AB  - Limb-girdle muscular dystrophies (LGMDs) is a heterogeneous group of muscular
      dystrophies that mostly affect the pelvic and shoulder girdle muscle groups. We
      report here a case of neuromuscular disease associated with Dupuytren's
      contracture, which has never been described before as cosegregating with an
      autosomal dominant type of inheritance. Dupuytren's contracture is a common
      disease, especially in Northern Europe. Comorbid conditions associated with
      Dupuytren's contracture are repetitive trauma to the hands, diabetes, and
      seizures, but it has never before been associated with neuromuscular disease. We
      hypothesize that patients may harbor mutations in genes with functions related to
      neuromuscular disease and Dupuytren's contracture development. 

PMID- 24024054
TI  - Spontaneous rupture of pyometra.
AB  - Spontaneous perforation is a very rare complication of pyometra. The clinical
      findings of perforated pyometra are similar to perforation of the
      gastrointestinal tract and other causes of acute abdomen. In most cases, a
      correct and definite diagnosis can be made only by laparotomy. We report two
      cases of diffuse peritonitis caused by spontaneous perforated pyometra. The first
      case is a 78-year-old woman with abdominal pain for which laparotomy was
      performed because of suspected incarcerated hernia. The second case is a 61-year
      old woman with abdominal pain for which laparotomy was performed because of
      symptoms of peritonitis. At laparotomy of both cases, 1 liter of pus with the
      source of uterine was found in the abdominal cavity. The ruptured uterine is also
      detected. More investigations revealed no malignancy as the reason of the
      pyometra. 

PMID- 24024055
TI  - Surface rendering of external genitalia of a fetus at the 32nd week of gestation
      affected by partial androgen insensitivity syndrome.
AB  - Objectives. To demonstrate the feasibility of the prenatal diagnosis of partial
      androgen insensitivity syndrome by 3D-4D ultrasound. Methods. To report prenatal
      diagnosis of partial androgen insensitivity syndrome at 32nd week of gestation by
      3D-4D ultrasound in a fetus with a 46XY karyotype, testing negative to the
      mutation analysis of SRY gene and the 5 alpha -reductase 2 gene (SRD5A2).
      Results. 3D-4D surface rendering allows the detection of external and internal
      genital malformations and can address the prenatal diagnosis of PAIS and can
      exclude associated complications. Conclusions. Prenatal diagnosis of PAIS allows
      an adequate parental counseling and an early optimal management of the condition,
      not only for the psychological and social reflections but also for the avoidance
      of complications and postnatal morbidity due to misdiagnosis or delays in the
      treatment of the genital ambiguity. 

PMID- 24024056
TI  - Maxillary and Frontal Bone Simultaneously Involved in Brown Tumor due to
      Secondary Hyperparathyroidism in a Hemodialysis Patient.
AB  - Brown tumors are rare focal giant cell lesions of the bone caused by primary
      hyperparathyroidism (HPT). Brown tumor was reported in 1891; it presents as the
      end-stage findings of HPT. Common involvements are skull and pelvic girdle. We
      describe a case of 46-year-old female hemodialysis patient, with secondary HPT in
      whom multiple masses lesions of the left maxillary sinus and frontal bone were
      radiologically suspected to be brown tumor. This unusual manifestation of
      secondary HPT can be expected to occur with increased longevity of patients with
      renal failure and illustrates the need to include brown tumor in the differential
      diagnosis. 

PMID- 24024057
TI  - Severe macular edema in patients with juvenile idiopathic arthritis-related
      uveitis.
AB  - Purpose. To report the onset of severe macular edema in adolescent female
      patients affected by juvenile idiopathic arthritis (JIA). Methods. Four female
      patients affected by JIA-related chronic anterior uveitis (CAU), complicated by
      severe macular edema, were retrospectively analyzed. Macular area was evaluated
      by fluorescein angiography and optical coherence tomography (OCT). Results. CAU
      was bilateral in three patients. Mean age of uveitis and arthritis onset was,
      respectively, 4.5 +/- 1.7 years and 6.0 +/- 3.9 years. All patients underwent
      cataract extraction surgery. Despite ocular inflammation being controlled by
      topical/systemic therapy, during adolescence (mean age of appearance/diagnosis:
      12.7 +/- 3.9 years) patients developed severe unilateral macular edema. OCT
      revealed massive macular thickening (range from 550  MU m to 1214  MU m).
      Conclusions. Macular edema appeared in female adolescent patients in eyes with
      long-dating CAU submitted to cataract surgery. In such patients, in presence of
      age-related microvascular changes due to the enhancer effect of sex hormones,
      cataract extraction should be a factor triggering the retinal complication. 

PMID- 24024058
TI  - Pseudomyxoma peritonei originating from an intestinal duplication.
AB  - Alimentary tract duplications are rare congenital anomalies. They most often
      become symptomatic in childhood and rarely undergo malignant transformation.
      Pseudomyxoma peritonei (PMP) is an equally uncommon condition, most frequently
      originating from a primary appendiceal mucinous neoplasm. We report an extremely
      unusual case of PMP arising from an intestinal duplication. A 67-year-old woman
      presented with vague upper abdominal pain, and, unexpectedly, explorative
      laparoscopy revealed diffuse jelly-like peritoneal implants. The
      histopathological diagnosis of a low-grade PMP or "disseminated peritoneal
      adenomucinosis" was made. At that moment, no primary tumor was found. During
      later surgery, a cystic lesion located in the mesentery of the small bowel could
      be resected. Histologically, the cyst wall clearly showed the concentric layering
      of a normal bowel wall. The mucosa, however, displayed a diffuse low-grade
      villous adenoma. We concluded that this histological picture was most consistent
      with a small intestinal duplication, containing a low-grade villous adenoma. The
      adenoma caused a mucocele, which subsequently leaked or ruptured, giving rise to
      noninvasive mucinous peritoneal implants or low-grade PMP, also known as
      "disseminated peritoneal adenomucinosis" (DPAM). 

PMID- 24024059
TI  - A Case of Monozygotic Twins: The Value of Discordant Monozygotic Twins in
      Goldenhar Syndrome-OMIM%164210.
AB  - Goldenhar syndrome is a rare developmental disorder characterised by hemifacial
      microsomia, epibulbar tumours, ear malformation, and vertebral anomalies. As
      monozygotic (MZ) twins are believed to be genetically identical, discordance for
      disease phenotype between MZ twins varies with craniofacial anomalies, cardiac,
      vertebral, and central nervous system defects sporadically. We report a case of
      monozygotic female twins discordant for Goldenhar syndrome with hemifacial
      microsomia and the dysplasia of auricular pinna. 

PMID- 24024060
TI  - Inferior Right Hepatic Vein: A Useful Anatomic Variation for Isolated Resection
      of Segment VIII.
AB  - Anatomical resection of segment VIII (SVIII) is one of the most difficult
      hepatectomies to perform. Although it is the best choice of surgical treatment
      for tumors located at SVIII, its feasibility can be compromised when the right
      hepatic vein (RHV) must be resected en bloc with SVIII. Herein we describe a case
      of a cirrhotic patient that was submitted to segmentectomy VIII in bloc with the
      main trunk of the RHV, due to hepatocellular carcinoma. The resection could only
      be performed because a well developed inferior right hepatic vein (IRHV) was
      present. Anatomical variations of the liver vascularization should be used by
      liver surgeons to improve surgical results. 

PMID- 24024061
TI  - An uncommon twist: isolated fallopian tube torsion in an adolescent.
AB  - We report a 13-year-old girl with bilateral paratubal cysts and left isolated
      fallopian tube torsion (IFTT). Paratubal cysts are uncommon in children, and IFTT
      is a rare complication. Awareness of this entity and prompt surgical intervention
      could potentially salvage the fallopian tube preserving fertility. 

PMID- 24024062
TI  - Delayed Soft Tissue Reconstruction with a Horizontal Rectus Abdominis
      Musculocutaneous Flap following Hip Exarticulation.
AB  - Coverage of large soft tissue defects at the hip region constitutes a challenge
      for plastic surgeons. We report the case of a 43-year-old female with necrotizing
      fasciitis of the right thigh, necessitating hip exarticulation and substantial
      debridement of necrotic tissue. An ipsilateral horizontal rectus abdominis
      myocutaneous (HRAM) flap was used to cover the defect. The reconstruction was
      carried out after the attempt of local tissue rearrangement. In light of the
      successful outcome, we propose that this flap be considered in the future
      planning of soft tissue reconstruction at the hip region. 

PMID- 24024063
TI  - Iatrogenic sinistral hypertension complicating screening colonoscopy.
AB  - Colonoscopy is widely accepted as the gold-standard screening technique for
      detecting malignancies in the distal gastrointestinal tract in patients with
      symptoms suggestive of colon cancer. However, this procedure is not without risk,
      including colonic perforation. We report a patient who was managed conservatively
      after colonoscopy induced perforation. Eighteen months after appearing to make a
      full recovery, he presented with an upper gastrointestinal bleed. Oesophago
      gastro-duodenoscopy (OGD) revealed large gastric fundal varices and computed
      tomography (CT) revealed splenic vein thrombosis. The ensuing left-sided
      (sinistral) hypertension explains the development of the fundal varices in the
      presence of normal liver function. At surgery, a persistent abscess cavity was
      identified and cultures from this site grew Streptococcus anginosus. Curative
      splenectomy was performed and the patient made a full recovery. We advocate more
      prompt operative intervention in selected cases of iatrogenic colonic perforation
      with primary repair to prevent late complications. 

PMID- 24024064
TI  - Autologous bone-marrow-derived-mononuclear-cells-enriched fat transplantation in
      breast augmentation: evaluation of clinical outcomes and aesthetic results in a
      30-year-old female.
AB  - Autologous fat transfer (lipofilling) is becoming an invaluable tool for breast
      augmentation as well as for breast reconstruction. Autologous lipofilling has
      several advantages, including biocompatibility, versatility, natural appearance,
      and low donor site morbidity. The main limitation is unpredictable fat graft
      resorption, which ranges from 25% to 80%, probably as a result of ischaemia and
      lack of neoangiogenesis. To obviate these disadvantages, several studies have
      searched for new ways of increasing the viability of the transplanted fat tissue.
      One promising approach is to enrich the fat graft with autologous bone-marrow
      derived mononuclear cells (BMMNCs) before transplantation. BMMNCs produce many
      angiogenic and antiapoptotic growth factors, and their secretion is significantly
      enhanced by hypoxia. All of these mechanisms of actions could be beneficial for
      the stimulation of angiogenesis in ischemic tissues by BMMNCs administration. In
      our aesthetic surgery practice, we use fat transplantation enriched with BMMNCs,
      which caused a significant improvement in survival of fat grafts, compared with
      that of traditional lipofilling. Our experience with freshly isolated autologous
      fat enriched with BMMNCs for breast augmentation procedures is presented. The
      concept of this surgical and tissue handling technique is based on ability of
      BMMNCs to stimulate blood vessel growth. 

PMID- 24024065
TI  - Small cell neuroendocrine carcinoma of the urinary tract successfully managed
      with neoadjuvant chemotherapy.
AB  - Introduction. Small cell neuroendocrine carcinomas of the urinary tract is an
      extremely rare entity and very few cases have been reported in the literature.
      Small cell neuroendocrine carcinoma of the urinary tract (SCC-UT) is the
      association between bladder and urinary upper tract-small cell carcinoma (UUT
      SCC). It characterized by an aggressive clinical course. The prognosis is poor
      due to local or distant metastases, and usually the muscle of the bladder is
      invaded. Case Presentation. We report a rare case of a 54-year-old Arab male
      native of moroccan; he is a smoker and was referred to our institution for
      intermittent hematuria. Following a diagnosis of small cell neuroendocrine
      carcinomas of the ureter and the bladder, thoracoabdominal-pelvic CT was done,
      and the staging of the tumor was done in the bladder (T2N0M0) and (T1N0M0) in the
      ureter. Neoadjuvant alternating doublet chemotherapy with ifosfamide/doxorubicin
      and etoposide/cisplatin was realized, and nephroureterectomy associated to a
      cystoprostatectomy was carried out. After 24 months of followup, no local or
      distant metastasis was detected. Conclusion. The purpose of this review is to
      present a rare case of pure small cell neuroendocrine carcinoma of the urinary
      tract and review the literature about the place of neoadjuvant chemotherapy in
      this rare tumors. 

PMID- 24024066
TI  - Inflammatory myofibroblastic bladder tumor in a patient with wolf-hirschhorn
      syndrome.
AB  - Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm described in several
      tissues and organs including genitourinary system, lung, head, and neck. The
      etiology of IMT is contentious, and whether it is a postinflammatory process or a
      true neoplasm remains controversial. To our knowledge, we report the first
      reported case of IMT of urinary bladder in a pediatric patient with Wolf
      Hirschhorn (WHS). We also review the literature about patients with associated
      neoplasia. 

PMID- 24024067
TI  - Nonleukemic ureteral granulocytic sarcoma presenting with unilateral urinary
      obstruction and hematuria.
AB  - Granulocytic sarcoma is an extramedullary tumor which is composed of myeloblasts
      and immature myeloid cells. It usually occurs in association with acute myeloid
      leukemia and most commonly involves skin, soft tissue, lymph nodes, bone, and
      periosteum. We report a case of isolated ureteral granulocytic sarcoma without
      hematologic manifestations. Our patient presented with bloody urine and left
      sided lumbar pain. Preoperative clinical and radiologic features raised the
      suspicion of an upper urinary tract transitional cell carcinoma, and he was
      scheduled for nephroureterectomy. However, perioperative pathologic feedback and
      the unusual endoscopic appearance of the tumor altered our surgical strategy
      towards segmental ureterectomy and ureteroneocystostomy. Eventual pathologic
      diagnosis was granulocytic sarcoma of the ureter. Postoperative workup failed to
      demonstrate any sign of an accompanying hematologic disorder. He started
      receiving the chemotherapy protocol of acute myeloblastic leukemia. To our
      knowledge, this is the first documented case of nonleukemic ureteral granulocytic
      sarcoma which came to attention due to urologic complaints. 

PMID- 24024068
TI  - Current status of neurointerventional activities in Korea.
AB  - Neurointervention which deals with neurovascular disease in brain, head-and-neck
      and spines are one of the rapidly evolving medical fields. Several indices
      representing neurointerventional activities are still increasing year-by-year in
      Korea. We review current trend in major neurovascular diseases requiring usage of
      specific medical devices and some issues related to administrative process of the
      government approval. 

PMID- 24024069
TI  - Recent update of guidelines for neurointerventional procedures.
AB  - Treatment guidelines of the neurointerventional procedures are continuously
      updated. However, these guidelines differ between countries and even medical
      societies within the same country because of the differing interests and patient
      groups. The differences between guidelines are confusing to many
      neurointerventionalists. Recently "Clinical Research Center for Stroke" in Korea
      updated "Clinical Practice Guidelines for Stroke" for the patients in Korea. So
      we introduce those guidelines and compare several recent guidelines of
      international medical societies for neurointerventionalists. 

PMID- 24024070
TI  - Clinical and radiologic results of endovascular coil embolization for cerebral
      aneurysm in young patients.
AB  - PURPOSE: This study is an overview of the clinical and radiologic outcomes of
      endovascular coil embolization for cerebral aneurysm in patients aged 40 years
      and younger. MATERIALS AND METHODS: Between January 2008 and June 2011, 218
      aneurysms were treated using endovascular coil embolization and followed up with
      cerebral angiography at least six months later. Twenty-one aneurysms occurred in
      patients aged 40 years and younger, while 197 occurred in 179 patients older than
      40 years. The clinical and radiologic results were retrospectively analyzed and
      compared between the two groups using the modified Rankin scale scores and the
      modified Raymond scale. RESULTS: Follow-up cerebral angiography revealed two
      (9.5%) major and two (9.5%) minor recanalized aneurysms in patients aged 40 years
      and younger, and six (3.0%) major and 35 (17.7%) minor recanalized aneurysms in
      patients older than 40 years. However, the differences between the groups were
      not statistically significant. The preoperative and postoperative mean modified
      Rankin scale scores at time for follow-up angiography were 1.14 and 0.19
      respectively for patients aged 40 years and younger, and 1.30 and 0.30
      respectively for patients older than 40 years. CONCLUSION: The younger patients
      had clinically favorable outcomes with tolerable angiographic follow-up results.
      More regular and long-term imaging follow-up is required for younger patients due
      to their longer life expectancy.

PMID- 24024071
TI  - Recanalization of acute intracranial artery occlusion using temporary
      endovascular bypass technique.
AB  - PURPOSE: The purpose of this study is to present our preliminary experience of
      the temporary endovascular bypass (TEB) technique using an Enterprise stent for
      recanalization of acute intracranial artery (IA) occlusion. MATERIALS AND
      METHODS: Patients treated by TEB were enrolled in this retrospective study from
      January 2009 to May 2010. All the procedures consist of temporary partial
      deployment and subsequent retrieval of Enterprise stent, supplemented by intra
      arterial infusion of urokinase (UK) and/or tirofiban. According to the
      thrombolysis in cerebral infarction (TICI) classification, recanalization was
      evaluated with initial and postprocedural angiography. Safety was evaluated
      related to the procedure and clinical outcomes were assessed by National
      Institute of Health Stroke Scale (NIHSS) score at discharge and modified Rankin
      scale (mRS) score at 3 months. RESULTS: Eleven patients (median NIHSS 12.8, mean
      age 61.6 years, male: female = 8:3) with acute IA occlusion were treated with
      TEB. All the patients presented with TICI 0, and the occluded vessel was the
      middle cerebral artery (n=7), the basilar artery (n=1), and the distal ICA
      occlusion (n = 3). IV infusion of tissue plasminogen activator (tPA) was done in
      4 patients and mechanical thrombolysis with intra-arterial UK was performed in 9.
      Recanalization was achieved in 73% (8 patients; TICI >= 2). There were no
      procedure-related complications except for two asymptomatic intracranial
      hemorrhages. Improvement (>= 4 points on the NIHSS) and good outcome (mRS <=2)
      after 90 days was shown in six patients (55%). One patient died 6 days after
      procedure. CONCLUSION: TEB may be a valuable treatment option in acute
      thromboembolic IA occlusion without stent implantation.

PMID- 24024072
TI  - Endovascular Coil Embolization of Distal Anterior Cerebral Artery Aneurysms:
      Angiographic and Clinical Follow-up Results.
AB  - PURPOSE: This study is an overview of the clinical and angiographic outcomes of
      patients who undergo treatment for distal anterior cerebral artery aneurysms.
      MATERIALS AND METHODS: Between January 2009 and March 2012, 444 cerebral
      aneurysms were treated using endovascular coil embolization at our institute.
      Among them, 217 aneurysms were followed-up with angiography at least six months
      later. Of these, there were 16 distal anterior cerebral artery (ACA) aneurysms in
      16 patients. We conducted a retrospective review of clinical and radiological
      follow-up results of all patients with distal ACA aneurysms. The clinical and
      angiographic outcomes were assessed using the modified Rankin scale (mRS) and the
      Raymond classification scale, respectively. RESULTS: The mean age was 54.7 +/-
      10.2 years (41-75 years). The mean follow-up period was 20.6 +/- 9.64 months (6
      37 months). Three patients presented with acute rupture. The average aneurysm
      size was 4.98 +/- 1.39 mm (3.0-8.1 mm), and eight of 16 aneurysms (50%) had
      aspect ratios < 2.0. All 16 patients presented with complete obliteration
      immediately after the procedure. However, two patients had procedure-related
      complications, one with coil extrusion to the subarachnoid space without
      hemorrhage and one with thromboembolism subsequent to chemical thrombolysis. In
      the follow-up angiography, one major and five minor recurrences (for a total of
      six recurrences, 37.5%) were detected. However, the differences between the ACA
      aneurysm group and others were not statistically significant. Clinical outcomes
      were good for all of the patients at the time of discharge (mean mRS: 0.25, 0 to
      1) and at the follow-ups (mean mRS: 0). CONCLUSION: Despite a comparatively high
      recurrence rate, the endovascular treatment of distal anterior cerebral aneurysms
      is feasible and has a good clinical outcome.

PMID- 24024073
TI  - Computational Fluid Dynamics of Intracranial and Extracranal Arteries using 3
      Dimensional Angiography: Technical Considerations with Physician's Point of View.
AB  - We investigate the potentials and limitations of computational fluid dynamics
      (CFD) analysis of patient specific models from 3D angiographies. There are many
      technical problems in acquisition of proper vascular models, in pre-processing
      for making 2D surface and 3D volume meshes and also in post-processing steps for
      display the CFD analysis. We hope that our study could serves as a technical
      reference to validating other tools and CFD results. 

PMID- 24024074
TI  - Neuroform-EZ Stent Modification for Facilitated Delivery during Intracranial
      Aneurysm Embosurgery.
AB  - The Neuroform EZ Stent System is a fourth generation intracranial aneurysm stent
      that utilizes an integrated navigation guidewire. While designed to facilitate
      stent delivery, the guidewire can rarely impede proper positioning of the stent.
      In this technical case report, severing the guidewire from the stent delivery
      system with surgical scissors was required for successful stent implantation. 

PMID- 24024075
TI  - Complex coil assisted single coil embolization for small intracranial aneurysm.
AB  - The purpose of the technical note is to introduce the complex coil assisted coil
      embolization method in the treatment of intracranial small aneurysm, in order to
      enhance the safety of the procedure. The first microcatheter was navigated into
      the aneurysm sac and the ultrasoft coil was used as the embolization coil. If the
      embolizations coil could not stay within the aneurysm sac smoothly, such as coil
      herniation into parent artery during the delivery process. The second
      microcatheter would be navigated to the aneurysm level in the parent artery.
      Another complex coil was delivered within the parent artery via the second
      microcatheter to provide the neck bridge effect in order to enhance the stability
      of embolization coil. Besides, the protection coil will not disturb the parent
      artery flow. While the embolization coil was put into the aneurysm sac smoothly
      under the help of complex protective coil, the protective coil was then withdrawn
      gently. We use the most magnified view, dual-plane approach simultaneously to
      observe the stability of embolization coil. The embolization coil would be
      detached without any evidence of coil motion or vibration. The new method could
      provide the physiological protective method, without leaving any protective
      device such as stent within the parent artery. 

PMID- 24024076
TI  - Onyx Embolization of Dural Arteriovenous Fistula, using Scepter C Balloon
      Catheter: a Case Report.
AB  - We report our experience using Onyx for embolization of dural arteriovenous
      fistula (DAVF) under dual lumen balloon catheter flow arrest. Transfemoral
      cerebral angiography revealed a superior sagittal sinus (SSS) DAVF that was
      supplied via multiple branches of the external carotid arteries, the right
      anterior cerebral arteries, and the meningeal branches of the internal carotid
      artery. There was no anterograde venous drainage through the SSS, and venous
      drainage was almost retrograde through the medullary and cortical veins. Under
      general anesthesia, a transvenous approach was utilized to place the
      microcatheter close to the fistula site. After intravenous embolization with
      various coils, DAVF was partially occluded; Balloon catheter gained access to the
      DAVF via the right middle meningeal artery. We injected Onyx through the Scepter
      C catheter, after which DAVF was nearly completely occluded. Balloon-assisted
      Onyx embolization is a feasible and effective approach for the management of
      DAVF. 

PMID- 24024077
TI  - Safe implementation of mechanical thrombectomy in acute stroke patients with
      major arterial occlusion and concomitant subdural hematoma.
AB  - Mechanical thrombectomy (MT) alone in cases of large-vessel acute ischemic stroke
      (AIS) with a concomitant subdural hematoma (SDH) seems feasible and safe, but
      there's still a lack of evidence in the clinical literature. We report three
      cases of AIS with SDH, of which MT was performed with successful recanalization
      and no major changes in SDH: two elderly men with acute traumatic SDH and one man
      with incidental chronic SDH. (1) A 67-year-old man with acute traumatic SDH in
      the right side developed right middle cerebral artery (MCA) stroke, (2) a 72-year
      old man with chronic SDH in the left side developed right MCA stroke, and (3) a
      76-year-old-man with acute traumatic SDH in the right side developed top-of
      basilar artery syndrome. As for AIS patients with a SDH, MT may be the only
      feasible and safe treatment option. 

PMID- 24024078
TI  - Multimodal Imaging Follow-up of a Thrombosed Developmental Venous Anomaly: CT, CT
      Angiography and Digital Subtraction Angiography.
AB  - We report a rare case of thrombosed developmental venous anomaly (DVA) in a 31
      year old male with hemorrhagic cerebral venous infarction at the initial clinical
      presentation. In this case, sequential CT, CT angiography and digital subtraction
      angiography demonstrated thrombotic obstruction of the venous drainage from DVA,
      its progressive recanalization and temporal evolution of the affected brain
      parenchyma. The relevant previous literatures were reviewed and summarized. 

PMID- 24024079
TI  - Double microcatheter-assisted coiling of a basilar artery fenestration aneurysm.

PMID- 24024080
TI  - Physical fighting among Egyptian adolescents: social and demographic correlates
      among a nationally representative sample.
AB  - Introduction. Adolescent interpersonal violence is a global public health
      problem, yet gaps remain in the epidemiologic literature on adolescent violence
      in low- and middle-income countries (LMIC). Prevalence rates and risk and
      protective factors reported in high-income countries may be different from those
      reported in LMICs. Culturally-relevant epidemiologic data is important in efforts
      aimed at addressing adolescent interpersonal violence in these countries.
      Methods. A cross-sectional study of Egyptian adolescent involvement in violent
      behavior was conducted. Data collected from a 2006 school-based survey initiative
      were used; participants were adolescents aged 11-17 (N = 5, 249). Some
      participants were excluded from the dataset due to incomplete data (N = 111)
      resulting in a final sample of 5,138. Bivariate and logistic regression analyses
      were run to determine demographic and social variables associated with
      participation in physical fighting. Results. Thirty-one percent of adolescents
      reported being involved in a physical fight. Previously reported risk factors for
      violent behavior among adolescents such as depressive symptoms (OR = 1.29; CI =
      1.11-1.50) and bullying victimization (OR = 2.44; CI = 2.12-2.83) were positively
      associated with violent behavior in the present study, while the more novel
      factor of sedentary behavior was also observed as having a positive association
      with violent behavior (OR = 1.43; CI = 1.21-1.69). Known protective factors such
      as helpful peers (OR = 0.75; CI = 0.62-0.90) and understanding parents (OR =
      0.67; CI = 0.56-0.81) were found to have negative associations with violent
      behavior in the present study, in addition to the counterintuitive protective
      effect of having fewer friends (OR = 0.75; CI = 0.60-0.92). Conclusions.
      Prevalence rates of adolescent interpersonal violence in Egypt are similar to
      rates in other LMICs. The high reported rates of depressive symptomatology and
      bully victimization along with their positive association with physical fighting
      suggest that interventions aimed at treating and preventing these problems may
      help mitigate the likelihood of adolescents engaging in violent behavior;
      involvement in appropriate physical activity in a safe environment may be
      beneficial as well. More research is needed to understand the observed protective
      factor of having fewer friends. 

PMID- 24024081
TI  - The effect of a conflict of interest disclosure form using closed questions on
      the number of positive conflicts of interest declared - a controlled study.
AB  - Objective. While declarations of conflicts of interest (COI) have become an
      integral part of medical articles, COIs are often not declared completely and
      accurately. One of several possible reasons for deficient COI declarations is the
      lack of standardized and comprehensive COI forms. In 2010, the International
      Committee of Medical Journal Editors (ICMJE) introduced a COI form using clear
      definitions and closed questions. Deutsches Arzteblatt (DA), the journal of the
      German Medical Association, adapted this form and implemented it in early 2011.
      However, it is unclear whether changing COI forms leads to more positive COI
      statements. Material and Methods. In a controlled pre-post design, positive COI
      statements were analyzed at three German medical journals: one had changed its
      COI form (DA), two had not: Deutsche Medizinische Wochenschrift (DMW) and
      Nervenarzt (Ner), both of whom used open questions in their forms. At the levels
      of both authors and articles, respectively, the proportion of positive COI
      declarations in orignal and review articles was recorded for volumes 2010 (before
      implementation of the new COI form at DA) and 2012 (after). The change in
      positive COI disclosures at the journals was compared. Chi-square tests were used
      to compare the figures by journal in 2010 versus 2012 and among DA, DMW, and Ner.
      Results and Discussion. While positive COI statements more than doubled at DA,
      there was no meaningful change in either of the control journals: In 2010, 19.1%
      [95% CI: 15.4-23.2] of all DA-authors submitted positive COI declarations,
      relative to 39.6% [35.0-44.5] in 2012, a factor of 2.1. At the level of articles,
      positive COI statements increased from 32.3% [23.7-42.0] to 70.1% [60.5-78.6]
      (factor 2.2). At DMW, positive declarations rose by a factor of 1.3 to 12.1% [9.7
      14.8] in 2012 at author level and by a factor of 1.3 to 19.4 [14.2-25.7] for
      articles. At Ner, figures fell: to 19.9% for authors [16.9-23.4] and 30.7% for
      articles [24.0-38.1] (both by a factor of 0.8). P-values for the comparison of
      positive COI statements between 2010 and 2012 were low at DA (p for both author
      and article level comparisons <0.00001) and considerably higher at DMW and Ner
      (all >0.05). Although this is not a randomized controlled study, the findings
      support the hypothesis that the steep increase in positive COI statements at DA
      from 2010 to 2012 is the result of its new COI form: Relative to two journals
      that had not modified their COI forms the effect size of the change was
      considerably higher at DA. Also, in contrast to DMW and Ner, p-values indicate
      that chance is unlikely to have played a major role in the change of positive COI
      statements at DA. Conclusions. COI forms employing closed questions based on
      clear definitions of conflicts of interests, such as those recommended by ICMJE
      and now used by Deutsches Arzteblatt, seem to be superior to less structured
      forms. These results require confirmation with other COI forms and at other
      journals. 

PMID- 24024082
TI  - DNA barcoding unveils skate (Chondrichthyes: Rajidae) species diversity in 'ray'
      products sold across Ireland and the UK.
AB  - Skates are widely consumed across the globe, but many large species are subject
      to considerable concern regarding their conservation and management. Within
      Europe such issues have recently driven policy changes so that, for the first
      time, reports of skate landings now have to be made under species-specific names.
      Total allowable catches have also been established for many groups, which have
      been set to zero for a number of the most vulnerable species (e.g., Dipturus
      batis, Raja undulata and Rostoraja alba). Whilst accurate species identification
      has become an important issue for landings, the sale of skates is still usually
      made under a blanket term of "skate" or "ray". The matter of identifying species
      of skate is further complicated by their morphologically conservative nature and
      the fact that they are commercially valued for their wings. Thus, before sale
      their bodies are usually discarded (i.e., "winged") and often skinned, making
      morphological identification impossible. For the first time, DNA barcoding (of
      the mitochondrial COI gene) was applied to samples of skate wings from retail
      outlets across the British Isles, providing insight into which species are sold
      for consumption. A total of 98 wing samples were analysed, revealing that six
      species were sold; blonde ray (Raja brachyura), spotted ray (Raja montagui),
      thornback ray (Raja clavata), cuckoo ray (Leucoraja naevus) small-eyed ray (Raja
      microocellata) and shagreen ray (Leucoraja fullonica). Statistical testing
      demonstrated that there were significant differences in the species sold in the
      distinct retail groups which suggests complex drivers behind the patterns of sale
      in skates. The results also indicate that endangered species are not commonly
      being passed on to consumers. In addition, the practice of selling skate wings
      under ambiguous labels is highlighted as it makes it extremely difficult for
      consumers to exercise a right to avoid species of conservation concern.
      Interestingly, a single retailer chain labelled their wings as originating from
      three smaller-growing species (generally to be considered of lower conservation
      concern); of the six samples analysed from this company a third were mislabelled
      and originated from the thornback ray (a larger species that is currently
      undergoing population declines). 

PMID- 24024083
TI  - Augmenting transcriptome assembly by combining de novo and genome-guided tools.
AB  - Researchers interested in studying and constructing transcriptomes, especially
      for non-model species, face the conundrum of choosing from a number of available
      de novo and genome-guided assemblers. None of the popular assembly tools in use
      today achieve requisite sensitivity, specificity or recovery of full-length
      transcripts on their own. Here, we present a comprehensive comparative study of
      the performance of various assemblers. Additionally, we present an approach to
      combinatorially augment transciptome assembly by using both de novo and genome
      guided tools. In our study, we obtained the best recovery and most full-length
      transcripts with Trinity and TopHat1-Cufflinks, respectively. The sensitivity of
      the assembly and isoform recovery was superior, without compromising much on the
      specificity, when transcripts from Trinity were augmented with those from TopHat1
      Cufflinks. 

PMID- 24024085
TI  - On some properties of the generalized Mittag-Leffler function.
AB  - This paper deals with the study of a generalized function of Mittag-Leffler type.
      Various properties including usual differentiation and integration, Euler(Beta)
      transforms, Laplace transforms, Whittaker transforms, generalized hypergeometric
      series form with their several special cases are obtained and relationship with
      Wright hypergeometric function and Laguerre polynomials is also established. 2000
      MATHEMATICS SUBJECT CLASSIFICATION: 33C45, 47G20, 26A33.

PMID- 24024084
TI  - The direct response of the gonads to cues of stress in a temperate songbird
      species is season-dependent.
AB  - The gonadotropin releasing hormone (GnRH) system in the hypothalamus is often
      considered the final point in integration of environmental cues as they pertain
      to the reproductive axis. However, cues such as stress and food availability are
      detectable in the plasma (as glucocorticoid and metabolic fuel fluctuations).
      Vertebrate gonads express glucocorticoid receptor, therefore we hypothesized that
      the gonads can detect and respond directly to cues of stress. We provide evidence
      here that, in addition to regulation by the brain, the gonads of European
      starlings (Sturnus vulgaris) respond directly to fluctuations in corticosterone
      and metabolic fuels by modulating sex steroid secretion. Using a 4-h gonad
      culture, we show that physiologically-relevant concentrations of corticosterone
      and metabolic stress (via use of the glucose utilization inhibitor 2-deoxy-D
      glucose and the fatty acid oxidation inhibitor ethyl 2-mercaptoacetate (2DG/MA))
      can directly decrease testosterone and estradiol secretion from luteinizing
      hormone and follicle-stimulating hormone (LH/FSH)-stimulated testes and ovaries.
      This effect is regulated seasonally. Prior to the breeding season, testes and
      ovaries respond to corticosterone and 2DG/MA by significantly decreasing gonadal
      steroid release. Within the breeding season, the testes do not respond to these
      cues of stress, while the ovaries respond only to corticosterone. This seasonal
      difference in response may be due in part to the influence of these cues of
      stress on gonadal neuropeptide expression: corticosterone upregulates GnIH
      expression in the testes while metabolic stress upregulates GnIH in the ovaries.
      Thus the gonads can directly respond to fluctuations in corticosterone and
      metabolic fuels during a time of critical importance to the onset of breeding. 

PMID- 24024086
TI  - Trade-offs in quality of life and survival with chemotherapy for advanced breast
      cancer: mature results of a randomized trial comparing single-agent mitoxantrone
      with combination cyclophosphamide, methotrexate, 5-fluorouracil and prednisone.
AB  - BACKGROUND: We evaluate trade-offs between quality of life (QoL) and survival
      improvement for two chemotherapy regimens in advanced breast cancer. We also
      report on the long-term survival of patients in the ANZ 8614 clinical trial.
      METHODS: A total of 391 patients were randomized to mitoxantrone (14 mg/m(2)
      intravenously every 21 days) or a combination of cyclophosphamide 100 mg/m(2) and
      prednisone 40 mg/m(2) orally days 1 to 14 plus methotrexate 40 mg/m(2) and 5
      fluorouracil 600 mg/m(2) intravenously days 1 and 8 every 28 days (CMFP). QoL was
      self-assessed on 14 linear analog scales. We computed the mean differences
      between the two treatments as products of the mean differences in global QoL,
      progression-free survival and overall survival. RESULTS: CMFP led to a higher
      overall tumor response (39% vs. 25%, P=0.004) and longer progression-free
      survival (PFS) (median 5.6 vs 3.9 months, P=0.02) but with significantly more
      toxicity from alopecia, mucositis, diarrhea, anemia and lethargy. Overall
      survival (OS) was similar in the two groups (median 10.1 vs 11.6 months, P=0.81).
      QoL over the first 12 weeks was rated better by patients on CMFP for mood
      (P=0.04), nausea and vomiting (P=0.01), and feeling sick (P=0.02) but worse for
      hair loss (P<0.0001). A weighted combination of individual QoL items favoured
      CMFP (subset score mean difference 2.4, P=0.03). A global QoL score tended to
      favour CMFP (global score mean difference 1.7, P=0.18). Quality-adjusted PFS was
      significantly longer with CMFP (mean 7.208 vs 5.965 months, P=0.04), but quality
      adjusted OS was not significantly different (mean 11.832 vs 11.315 months,
      P=0.57). CONCLUSION: Despite the greater toxicity, the superior antitumor
      activity of CMFP led to an overall improvement in quality-adjusted PFS. In
      advanced breast cancer, in clinical decision making about treatment for
      palliative intent, the principle used to assess trade-offs between antitumor
      efficacy and toxicity remains relevant and applicable to all modern therapeutic
      agents.

PMID- 24024087
TI  - Individual quality of life in patients with multiple myeloma.
AB  - OBJECTIVE: The situation of patients with multiple myeloma, whose treatment often
      implies high-dose chemotherapy and stem cell transplantation that can be
      associated with severe symptoms and psychological distress, has gained attention
      in recent psychooncological research. This study followed an idiographic approach
      in order to identify the areas of life most relevant for the interviewed myeloma
      patients' quality of life (QoL) as well as their current satisfaction with these.
      METHODS: 64 patients took part in semi-structured interviews according to the
      SEIQoL-DW Manual (Schedule for the Evaluation of Individual Quality of Life -
      Direct Weighting). Visual analogue scales (VAS) were used to gain additional
      information about a general assessment of the present QoL. Qualitative data
      evaluation preceded quantitative processing. Groups were compared according to
      the time elapsed since diagnosis regarding specified areas of life, satisfaction
      with these and their relative weighting. SEIQoL-DW-indices were correlated to the
      VAS to reflect on an interindividually comparable parameter. RESULTS: Personal
      social relationships were mentioned significantly more often as important for QoL
      than health-related aspects, and in direct comparison were weighted significantly
      stronger. Regarding the change of areas relevant for QoL over the time elapsed
      since diagnosis, there was a significant difference between groups concerning the
      area of spirituality. Satisfaction differed significantly between groups for the
      field of leisure. CONCLUSION: The results for the interviewed patients with
      multiple myeloma point out the need to take into account the importance of social
      and individual aspects when reflecting on QoL. Similar findings have been
      reported for different samples. The relevance of an individualized approach is
      illustrated by the fact that individually named areas of life were rated
      comparatively strongly in their importance for the patients' QoL. An overall
      assessment for the current QoL by means of VAS is regarded as an adequate
      supplement to the SEIQoL-Profile and an alternative to the SEIQoL-DW-Index.

PMID- 24024088
TI  - A large thigh mass: a blood clot or a rare skeletal muscle metastasis from renal
      cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma (RCC) is a tumor known for its unusual
      presentations and high rate of metastasis. Metastasis to lung, liver, bone and
      brain are common, but to skeletal muscle(SM) is very rare. Because only 11% of
      the RCC metastases to SM present after 10 years of initial presentation, there is
      no general consensus for its annual surveillance. METHODS: We report a case of a
      58 year old male with a history of RCC, initially diagnosed 11 years ago, who
      presented with a large SM mass. A large mass measuring more than 25 cm was
      located in left posterior thigh and was present for more than a year. It
      initially was diagnosed as a large blood clot and was treated with warfarin for
      more than 6 months. Clinical work up including FDG-PET/CT and MRI raised the
      possibility of a tumor, but a negative biopsy made the diagnosis uncertain.
      Because of high suspicion for a tumor, patient underwent a complete resection of
      the mass. RESULTS: The resected mass measuring 28 * 18 * 7 cm was detailed as the
      largest skeletal muscle metastasis from RCC ever reported. CONCLUSION: This case
      emphasizes the importance of maintaining a high suspicion for metastasis even in
      less common metastatic sites mainly in patients with a history of RCC. It also
      highlights the importance of annual surveillance for metastasis in patients with
      RCC even after 10 years of initial presentation using FDG-PET/CT.

PMID- 24024089
TI  - Diagnostic value of triple-phase bone scintigraphy for the diagnosis of infection
      around antibiotic-impregnated cement spacers.
AB  - INTRODUCTION: Two-stage revision arthroplasty is today considered as the gold
      standard for control of chronic deep prosthetic infection. Although the revision
      arthroplasty should only be considered when infection is eliminated, the
      diagnosis of residual infection prior to the revision remains a challenging
      problem. MATERIALS AND METHODS: We evaluated triple-phase bone scintigraphy as a
      useful diagnostic test for the detection of residual infection around the
      antibiotic-impregnated cement spacer in patients waiting for the second-stage
      revision hip or knee arthroplasty. Increased uptake of radioisotope in all three
      phases was considered positive for infection. The final diagnosis was based on
      histopathological results in addition to microbiologic examinations of surgical
      specimens. RESULTS: Histopathological examination showed positive in 17 and
      negative in 13 out of 30 examinations. Among 17 samples positive for
      histopathology, there were only 4 samples positive for bacterial culture. All
      samples negative for histopathology showed negative for bacterial culture. The
      positive and negative predictive values of triple-phase bone scintigraphy for the
      presence of infection were 80% and 90%, respectively. The diagnostic sensitivity
      was 94% and the specificity was 69%. CONCLUSION: Triple-phase bone scintigraphy
      was useful in the diagnosis of infection around the articulating cement spacer.
      In particular, when triple-phase bone scintigraphy shows negative, the residual
      infection around the cement spacer is unlikely.

PMID- 24024090
TI  - beta-galactosidase stability at high substrate concentrations.
AB  - Enzymatic synthesis of galacto-oligosaccharides is usually performed at high
      initial substrate concentrations since higher yields are obtained. We report here
      on the stability of beta-galactosidase from Bacillus circulans at 25, 40, and 60
      degrees C in buffer, and in systems with initially 5.0 and 30% (w/w) lactose. In
      buffer, the half-life time was 220 h and 13 h at 25 and 40 degrees C,
      respectively, whereas the enzyme was completely inactivated after two hours at 60
      degrees C. In systems with 5.0 and 30% (w/w) lactose, a mechanistic model was
      used to correct the oNPG converting activity for the presence of lactose,
      glucose, galactose, and oligosaccharides in the activity assay. Without
      correction, the stability at 5.0% (w/w) lactose was overestimated, while the
      stability at 30% (w/w) lactose was underestimated. The inactivation constant k d
      was strongly dependent on temperature in buffer, whereas only a slight increase
      in k d was found with temperature at high substrate concentrations. The enzyme
      stability was found to increase strongly with the initial substrate
      concentrations. The inactivation energy E a appeared to be lower at high initial
      substrate concentrations. 

PMID- 24024091
TI  - Lower limb body composition is associated to knee passive extension torque-angle
      response.
AB  - PURPOSE: People vary in flexibility regarding maximum joint angle, resistance to
      stretch and mechanical responses during stretching exercises. Body composition
      (BC) has been been mentioned as one of the factors for flexibility differences.
      The aim of this study was to determine how body composition and anthropometric
      measures of the lower limb is associated with passive knee extension (PKE) torque
      angle (T-A) response. METHODS: Twenty-five male subjects with poor flexibility
      performed a maximal PKE repetition (velocity of 2 degrees /s; 90 seconds in the
      static phase). Knee passive T-A, vastus medialis and semitendinosous
      electromyographic activity were recorded during the protocol. Viscoelastic stress
      relaxation (VSR) amplitude, knee passive stiffness (KPS), lower limb body
      composition assessed by dual energy x-ray absorptiometry, and anthropometry
      measures were determined. RESULTS: Thigh skeletal muscle and bone mass, as well
      as thigh perimeter, showed a moderated correlation with passive torque (r = 0.45;
      r = 0.6; r = 0.59, respectively), joint angle (r = 0.46; r = 0.5; r = 0.5), and
      VSR (r = 0.46; r = 0.49; r = 0.5). Thigh skeletal muscle was also correlated with
      KPS (r = 0.42). All these correlations were statistically significant (p < 0.05).
      CONCLUSIONS: Passive knee extension T-A was found to be moderately correlated
      with lower limb BC. In particular, thigh perimeter and skeletal muscle mass were
      associated with knee passive stiffness and viscoelastic stress relaxation. More
      research is needed to understand what influences joint maximum angle, resistance
      to stretch and mechanical response to stretching.

PMID- 24024093
TI  - Diversity of fungal flora in raw milk from the Italian Alps in relation to
      pasture altitude.
AB  - The present paper explores the diversity of mycobiota inhabiting raw milk sampled
      at different altitudes (1400 m, 1800 m, 2200 m) from cows grazing Alpine pastures
      of Valle d'Aosta (North-Western Italian Alps). To this aim, multilocus sequencing
      was performed at barcodes commonly used for fungal identification (ITS1, D1/D2
      domains of the 26S rRNA gene, and part of the beta-tubulin gene). A total of 31
      species were detected, most of them yeasts, followed by moulds and by 2 sequences
      of macroscopic fungi. Several yeasts and moulds were well-characterized
      inhabitants of the dairy environment, known to positively contribute to
      cheesemaking. Among these, Candida was the most represented genus with a tendency
      to cluster at the highest altitudes (6 over 8 observations at >= 1800 m), and
      Kluyveromyces marxianus the most abundant single species, retrieved at all
      altitudes. The environmental ascomycetous Atrotorquata lineata, never put in
      relation with food nor described outside North-America, was another species among
      those most frequently retrieved and was detected in 6 milks at 1400 and 1800 m.
      The remaining fungi, in general never reported in milk, were mostly
      environmental. Many of them resulted associated with plants as pathogens or
      symbionts. Finally, the highest sampled altitude yielded a significant fungal
      diversity (17 species). This work enlarges the knowledge of fungal consortia
      inhabiting raw milk and introduces microbial ecology among the altitude-dependent
      factors, in the composition of Alpine pastures, with the potential of shaping the
      properties of milks and cheeses, together with the already described physical,
      chemical and botanical variables. 

PMID- 24024094
TI  - New pulse wave measurement method using different hold-down wrist pressures
      according to individual patient characteristics.
AB  - In traditional Chinese and Korean medicine, doctors first observe a patient's
      pulse by gently and strongly pressing their fingers onto the wrist, and then make
      a diagnosis based on the observed pulse waves. The most common method to
      implement this diagnostic technique is to mechanically extract the pulse waves by
      applying a fixed range of pressures for all patients. However, this method does
      not consider the patients individual characteristics such as age, sex, and skin
      thickness. In the present study, we propose a new method of pulse wave extraction
      that incorporates the personal characteristics of the patients. This method
      measures the pulse wave signal at varying hold-down pressures, rather than
      applying a fixed hold-down pressure for all patients. To compare this new
      technique with existing methods, we extracted pulse waves from 20 subjects, and
      then determined the actual applied pressure at each step, the coefficient of
      floating and sinking pulse (CFS), and the distinction of floating/sinking pulse
      for each group. Consequently, each subject had a different pressure range in our
      proposed method, whereas all subjects had a similar pressure range in the
      existing method. Four of 20 subjects exhibited different floating/sinking pulse
      patterns due to the value of the first pressure step and the range of hold-down
      pressures. These four subjects were categorized as overweight based on BMI. In
      addition, the moving distance of the proposed method was longer than the existing
      method (p = 0.003, paired t-test), and the correlation coefficient between CFS
      values of two different methods was 0.321, indicating that there was no
      correlation. 

PMID- 24024092
TI  - Involvement of free radicals in breast cancer.
AB  - Researchers have recently shown an increased interest in free radicals and their
      role in the tumor microenvironment. Free radicals are molecules with high
      instability and reactivity due to the presence of an odd number of electrons in
      the outermost orbit of their atoms. Free radicals include reactive oxygen and
      nitrogen species, which are key players in the initiation and progression of
      tumor cells and enhance their metastatic potential. In fact, they are now
      considered a hallmark of cancer. However, both reactive species may contribute to
      improve the outcomes of radiotherapy in cancer patients. Besides, high levels of
      reactive oxygen species may be indicators of genotoxic damage in non-irradiated
      normal tissues. The purpose of this article is to review recent research on free
      radicals and carcinogenesis in order to understand the pathways that contribute
      to tumor malignancy. This review outlines the involvement of free radicals in
      relevant cellular events, including their effects on genetic instability through
      (growth factors and tumor suppressor genes, their enhancement of mitogenic
      signals, and their participation in cell remodeling, proliferation, senescence,
      apoptosis, and autophagy processes; the possible relationship between free
      radicals and inflammation is also explored. This knowledge is crucial for
      evaluating the relevance of free radicals as therapeutic targets in cancer. 

PMID- 24024095
TI  - Population genetic structure of the messmate pipefish Corythoichthys
      haematopterus in the northwest pacific: evidence for a cryptic species.
AB  - The population genetic structure of the messmate pipefish, Corythoichthys
      haematopterus, in the northwest Pacific was investigated based on the partial
      mitochondrial DNA cytochrome b (589 bp) and 16S rRNA (528 bp) region sequences of
      108 individuals collected from six sites along the coast of the Japanese
      archipelago and one site on Mactan Island, the Philippines. A total of 60 and 28
      haplotypes were obtained from the cytochrome b and 16S rRNA regions,
      respectively. Two genetically distinct lineages were detected: lineage A and B,
      which are separated by mean pairwise genetic distances of 23.3 and 14.1% in the
      partial cytochrome b and 16S rRNA genes, respectively. Such a huge genetic
      divergence between lineages, which is comparable to or even higher than the
      interspecific level, and the difference in their geographical distributions and
      habitat preferences suggests that they are distinct species, although there is no
      marked difference in their morphology. Haplotype network and gene and nucleotide
      diversity statistics indicate that the two lineages have different biogeographic
      histories: lineage A experienced rapid population expansion after a population
      bottleneck whereas lineage B has a long evolutionary history in a large stable
      population. In contrast, the levels of genetic variation among populations are
      relatively low in both lineages, probably because of frequent gene flow among
      populations resulting from the dispersal of pelagic larvae by the Kuroshio
      Current. These results indicate that past climatic events and contemporary
      oceanographic features have played a major role in establishing the population
      genetic structure of C. haematopterus. 

PMID- 24024096
TI  - Characterization of a new oxidant-stable serine protease isolated by functional
      metagenomics.
AB  - A novel serine protease gene, SBcas3.3, was identified by functional screening of
      a forest-soil metagenomic library on agar plates supplemented with AZCL-casein.
      Overproduction in Escherichia coli revealed that the enzyme is produced as a 770
      amino-acid precursor which is processed to a mature protease of ~55 kDa. The
      latter was purified by affinity chromatography for characterization with the
      azocasein substrate. The enzyme proved to be an alkaline protease showing maximal
      activity between pH 9 and 10 and at 50 degrees C. Treatment with the chelating
      agent ethylenediaminetetraacetic acid irreversibly denatured the protease, whose
      stability was found to depend strictly on calcium ions. The enzyme appeared
      relatively resistant to denaturing and reducing agents, and its activity was
      enhanced in the presence of 10 ml/l nonionic detergent (Tween 20, Tween 80, or
      Triton X-100). Moreover, SBcas3.3 displayed oxidant stability, a feature
      particularly sought in the detergent and bleaching industries. SBcas3.3 was
      activated by hydrogen peroxide at concentrations up to 10 g/l and it still
      retained 30% of activity in 50 g/l H2O2. 

PMID- 24024097
TI  - Therapeutic hypothermia in cerebral air embolism: a case report.
AB  - BACKGROUND: Cerebral air embolism is a life-threatening complication of various
      diagnostic and therapeutic procedures. Hyperbaric oxygenation is considered to be
      the cornerstone of its treatment. CASE DESCRIPTION: We report a patient with
      cerebral air embolism after endoscopy of a perineal abscess. Immediate CT imaging
      confirmed the diagnosis and MRI showed cortically localized areas of restricted
      diffusion along the gyri. Since hyperbaric oxygenation was not available,
      moderate hypothermia was applied for neuroprotection. CONCLUSION: This case
      illustrates a rare complication of endoscopic interventions, and imaging
      characteristics of cerebral air embolism were described. Furthermore, we discuss
      the potential utility of therapeutic hypothermia in cerebral air embolism.

PMID- 24024098
TI  - Comparison of the clonality of urothelial carcinoma developing in the upper
      urinary tract and those developing in the bladder.
AB  - PURPOSE: To identify the origin of synchronous and metachronous urothelial
      carcinoma (UC) of the bladder and upper urinary tract to get a better
      understanding of the basic mechanism behind the multifocality of UC, which may
      provide a sound bases for the future development of new strategies for detection,
      prevention and therapy. METHODS: Six patients with UC of the bladder and
      synchronous or metachronous UC of the upper urinary tract were studied. Genetic
      analysis involving the study of loss of heterozygosity (LOH) has been evaluated
      on their tumours using well characterised and new markers of UC (D9S171, D9S177,
      D9S303 and TP53). RESULTS: Five of the six patients demonstrated informative
      results. Four of five (80%) of patients had synchronous or metacharonous UC
      tumour and showed patterns of LOH consistent with tumorigenesis from monoclonal
      tumour origin. One of five (20%) patients exhibited a LOH consistent with
      oligoclonal tumorigenesis. CONCLUSION: These findings suggest that both the
      monoclonal and field cancerization theory of tumorigenesis may play a role in
      tumors of the urothelial tract. However, more data is needed.

PMID- 24024099
TI  - Intracranial extravasation of contrast medium during diagnostic CT angiography in
      the initial evaluation of subarachnoid hemorrhage: report of 16 cases and review
      of the literature.
AB  - INTRODUCTION: Three-dimensional CT angiography (3D-CTA) is increasingly used in
      the initial evaluation of subarachnoid hemorrhage (SAH). However, there is a risk
      of aneurysm re-rupture in the hyperacute phase. We sought to clarify the
      incidence of re-rupture and characterize the subgroup in which extravasation of
      contrast media was seen on 3D-CTA. METHODS: We examined the records of 356
      consecutive patients presenting to our institution with non-traumatic SAH between
      October 2003 and December 2011. After resuscitation, patients with poor grade SAH
      underwent CT then 3D-CTA while sedated, mechanically ventilated and with a target
      systolic blood pressure of 120 mmHg. RESULTS: 336 patients underwent 3D-CTA; 20
      died without return of spontaneous circulation. Extravasated contrast medium was
      seen in 16 (4.8%), 15 (4.5%) at the initial evaluation. Their World Federation of
      Neurosurgical Societies Grade was V; one patient was resuscitated from cardiac
      arrest. The mean times from onset to arrival and to CTA were 43.7 minutes and
      71.8 minutes, respectively. Ten patients (62.5%) had episodes suggestive of
      aneurysm re-rupture before 3D-CTA. Surgical clipping, evacuation of hematoma and
      wide decompressive craniectomy was completed in six patients and one underwent
      coil embolization. Two of 16 patients survived: one with moderate disability and
      one made a good recovery. CONCLUSIONS: Contrast extravasation was detected by 3D
      CTA in 4.5% of cases despite intensive resuscitation, suggesting that continuous
      or intermittent rebleeding may occur frequently in the hyperacute phase. The
      consequences of rebleeding are devastating; however, favorable results can be
      obtained with immediate aneurysm repair with decompression and intensive
      neurocritical care.

PMID- 24024101
TI  - Efficient material flow in mixed model assembly lines.
AB  - In this study, material flow from decentralized supermarkets to stations in mixed
      model assembly lines using tow (tugger) trains is investigated. Train routing,
      scheduling, and loading problems are investigated in parallel to minimize the
      number of trains, variability in loading and in routes lengths, and line-side
      inventory holding costs. The general framework for solving these problems in
      parallel contains analytical equations, Dynamic Programming (DP), and Mixed
      Integer Programming (MIP). Matlab in conjunction with LP-solve software was used
      to formulate the problem. An example was presented to explain the idea. Results
      which were obtained in very short CPU time showed the effect of using time buffer
      among routes on the feasible space and on the optimal solution. Results also
      showed the effect of the objective, concerning reducing the variability in
      loading, on the results of routing, scheduling, and loading. Moreover, results
      showed the importance of considering the maximum line-side inventory beside the
      capacity of the train in the same time in finding the optimal solution. 

PMID- 24024100
TI  - Comparison of infarct volume and behavioral deficit in Wistar Kyoto and
      spontaneously hypertensive rat after transient occlusion of the middle cerebral
      artery.
AB  - Rodent models of focal cerebral ischemia are important tools in experimental
      stroke research. Such models have proven instrumental for the understanding of
      injury mechanisms in cerebral stroke and helped to identify potential new
      therapeutic options. A plethora of neuroprotective substances have been shown to
      be effective in preclinical stroke research but failed to prove effectiveness in
      subsequent clinical trials. Interestingly, preclinical studies have shown that
      neuroprotective agents are selectively effective in different rat strains. The
      underlying mechanisms for this discrepancy are so far unknown, but differences in
      initial stroke volume with concomitant neuroinflammatory processes in the
      expanding stroke area might be relevant. In the current project, we compared the
      stroke volume and behavioral outcome between Wistar Kyoto (WKY) and spontaneously
      hypertensive rats (SHR), subjected to transient middle cerebral artery occlusion
      (tMCAO) for 1 h, followed by 23 h reperfusion. We further analyzed the expression
      of well-known pro-inflammatory mediators in the cortical peri-infarct area region
      using a TTC-based isolation approach. Initial reduction of local cerebral blood
      flow was comparable between both strains. Mean infarct volume and the extent of
      tMCAO-provoked functional deficits did not differ between WKY and SHR rats.
      Furthermore, the induction of pro-inflammatory mediators, among CCL3 and CCL5, in
      the isolated ischemic peri-infarct area region was equal in both rat strains. We
      were able to demonstrate that stroke outcome is comparable 23 h after transient
      MCAO in WKY and SHR rats. Future studies have to show whether this observation
      confirms in the long-term, and which factors contribute to differences observed
      with respect to therapeutic responsiveness. 

PMID- 24024102
TI  - Preliminary results in anterior cervical discectomy and fusion with an
      experimental bioabsorbable cage - clinical and radiological findings in an ovine
      animal model.
AB  - BACKGROUND: Bioabsorbable implants are not widely used in spine surgery. This
      study investigated the clinical and radiological findings after anterior cervical
      discectomy and fusion (ACDF) in an ovine animal model with an experimental
      bioabsorbable cage consisting of magnesium and polymer (poly-epsilon
      caprolactone, PCL) in comparison to a tricortical bone graft as the gold standard
      procedure. MATERIALS AND METHODS: 24 full-grown sheep had ACDF of C3/4 and C5/6
      with an experimental bioabsorbable implant (magnesium and PCL) in one level and
      an autologous tricortical bone graft in the second level. The sheep were divided
      into 4 groups (6 sheep each). After 3, 6, 12, or 24 weeks postoperatively, the
      cervical spines were harvested and conventional x-rays of each operated segment
      were conducted. The progress of interbody fusion was classified according to a
      three-point scoring system. RESULTS: There were no operation related
      complications except for one intraoperative fracture of the anterior superior
      iliac spine and two cases of screw loosening and sinking, respectively. In
      particular, no vascular, neurologic, wound healing or infectious problems were
      observed. According to the time of follow-up, both interbody fusion devices
      showed similar behaviour with increasing intervertebral osseointegration and
      complete arthrodesis in 10 of 12 (83.3%) motion segments after 24 weeks.
      CONCLUSIONS: The bioabsorbable magnesium-PCL cage used in this experimental
      animal study showed clinically no signs of incompatibility such as infectious or
      wound healing problems. The radiographic results regarding the osseointegration
      are comparable between the cage and the bone graft group.

PMID- 24024103
TI  - Passive carriage of rabies virus by dendritic cells.
AB  - The rabies virus (RABV) is highly neurotropic and it uses evasive strategies to
      successfully evade the host immune system. Because rabies is often fatal,
      understanding the basic processes of the virus-host interactions, particularly in
      the initial events of infection, is critical for the design of new therapeutic
      approaches to target RABV. Here, we examined the possible role of dendritic cells
      (DCs) in the transmission of RABV to neural cells at peripheral site of exposure.
      Viral replication only occurred at a low level in the DC cell line, JAWS II,
      after its infection with either pathogenic RABV (CVS strain) or low-pathogenic
      RABV (ERA strain), and no progeny viruses were produced in the culture
      supernatants. However, both viral genomic RNAs were retained in the long term
      after infection and maintained their infectivity. The biggest difference between
      CVS and ERA was in their ability to induce type I interferons. Although the ERA
      infected JAWS II cells exhibited cytopathic effect and were apparently killed by
      normal spleen cells in vitro, the CVS-infected JAWS II cells showed milder
      cytopathic effect and less lysis when cocultured with spleen cells. Strongly
      increased expression of major histocompatibility complex classes I, costimulatory
      molecules (CD80 and CD86), type I interferons and Toll- like receptor 3, and was
      observed only in the ERA-inoculated JAWS II cells and not in those inoculated
      with CVS. During the silencing of the cellular immune response in the DCs, the
      pathogenic CVS strain cryptically maintained an infectious viral genome and was
      capable of transmitting infectious RABV to permissive neural cells. These
      findings demonstrate that DCs may play a role in the passive carriage of RABV
      during natural rabies infections. 

PMID- 24024104
TI  - Henneguya sp. in yellowfin goby Acanthogobius flavimanus from the San Francisco
      Estuary.
AB  - Myxozoan spores were observed in yellowfin goby Acanthogobius flavimanus
      collected from Suisun Marsh, San Francisco Estuary (SFE). Although
      histopathological changes associated with the parasite were not observed, the
      spores formed plasmodia that partially blocked the gastric and intestinal mucosa
      and gut lumen and may affect the perfomance and survival of the yellowfin goby.
      Morphological features of the spores resembled Henneguya sp. and molecular
      analysis of the 18S ribosomal DNA (Domain III) confirmed close similarity to H.
      rhinogobii and H. pseudorhinogobii isolated from the Japanese freshwater goby.
      The yellowfin goby myxozoan however, is likely an undescribed species based on
      phylogenetic analysis and morphologic features. Detailed description of
      vegetative and spore stages are currently lacking for proposal to a new species
      of Henneguya. A specific PCR test was developed, which confirmed a 100%
      prevalence of the parasite among randomly collected gobies in group 1 (N = 30)
      and group 2 (N = 15) at termination of the study at one month in captivity. The
      myxozoan was also detected from 18 gobies (12%) that died in the first group
      within two weeks in captivity. Apparently healthy gobies that served as controls
      did not reveal the presence of the myxozoan by PCR. This study documents the
      occurrence of a potentially new species of myxozoan in the yellowfin goby and
      underscores the detection of a parasitic infection in an introduced fish in the
      SFE. Although the pathogenesis of the myxozoan was not assessed and the
      prevalence as reported here is restricted to a comparatively small collection
      site in Suisun slough, the reemergence, identification, and ecological relevance
      of the parasite on goby populations in the SFE may be investigated in the future
      using the specific diagnostic tool developed in this study. 

PMID- 24024105
TI  - Characterization of a novel polyclonal anti-hypusine antibody.
AB  - The translation factor eIF5A is the only protein known to contain the amino acid
      hypusine, which is formed posttranslationally. Hypusinated eIF5A is necessary for
      cellular proliferation and responses to extracellular stressors, and has been
      proposed as a target for pharmacologic therapy. Here, we provide the first
      comprehensive characterization of a novel polyclonal antibody (IU-88) that
      specifically recognizes the hypusinated eIF5A. IU-88 will be useful for the
      investigation of eIF5A biology and for the development of assays recognizing
      hypusinated eIF5A. 

PMID- 24024106
TI  - Effect of salting-out on distribution behavior of di(2-ethylhexyl) phthalate and
      its analogues between water and sediment.
AB  - A higher enrichment of organic pollutant, di(2-ethylhexyl) phthalate (DEHP) was
      found in estuary of Oyabe River and Jinzu River, Japan. Based on this, the
      distribution of DEHP between water and bed sediment was investigated as a model
      of organic pollutant through both the field investigation and laboratory
      experiment. The laboratory experiment was performed to examine the effect of
      seawater, organic matter in sediment and hydrophobicity (log K ow ) of organic
      pollutants. The result showed that salting-out effect due to the high salinity in
      seawater and organic matter in sediment contributed towards the increasing of
      DEHP distribution between water and sediment. Furthermore, the hydrophobicity of
      organic pollutant also enhances the distribution between water and sediment to a
      higher magnitude in the presence of seawater. 

PMID- 24024108
TI  - An optimization method for parameter extraction of metals using modified Debye
      model.
AB  - The Modified Debye Model (MDM) parameters for five metals are presented. A
      nonlinear optimization algorithm has been developed in order to extract the
      parameters for the metals. The extracted parameters have been used to determine
      the complex relative permittivity of the metals in optical and near-IR region of
      electromagnetic spectrum. The obtained results have been compared with the
      experimental values and an excellent agreement has been found. 

PMID- 24024107
TI  - Relationship between total homocysteine, total cholesterol and creatinine levels
      in overt hypothyroid patients.
AB  - Hypothyroidism is associated with an increased risk for cardiovascular disease,
      which can not be fully explained by the atherogenic lipid profile, particularly
      total cholesterol and LDL-C, and other pathogenic factors may be involved. Plasma
      total homocysteine (tHcy) is an independent risk factor for cardiovascular
      disease and accelerated atherosclerosis. The aim of this study was to investigate
      the serum total homocysteine (tHcy) levels and its relation to total cholesterol,
      creatinine and thyroid hormones fT3, fT4 and TSH levels in overt hypothyroid
      patients compared to control subjects. In this study thirty recently diagnosed,
      non-treated overt hypothyroid patients (f=27, m=3) and twenty normal volunteers
      control (f=18, m=2) were included and subjected to determination of serum tHcy by
      enzyme immunoassay (EIA) technique, fT3, fT4 and TSH by Elecsys cobas e 601
      analyzer, total cholesterol by enzymatic method and creatinine by kinetic method.
      The data was statistically analysed by SPSS-10 and p values less than 0.05 were
      considered significant.Our results showed that there were a significant increase
      of tHcy, TSH, T.cholesterol and creatinine levels by 113%, 12-folds, 58% and 54%,
      respectively, and a significant decrease of fT4 and fT3 levels by 49.6% and 56.4%
      , respectively, in hypothyroid patients than in control group. For tHcy (Mean+/
      SD, 24.45+/-5.50 MUmol/l vs 11.48+/-3.03 MUmol/l, respectively; P < 0.001). tHcy
      was significantly positively correlated with TSH, creatinine and age and
      negatively correlated with free thyroxine (fT4) and no significant correlations
      with fT3 and T.cholesterol. In conclusion, our study confirmed the observation of
      elevated serum tHcy, T.cholesterol and creatinine in overt hypothyroidism and the
      presence of an inverse relation between tHcy with fT4 and a positive relation
      with TSH. 

PMID- 24024109
TI  - Improvement of somatic embryogenesis and plantlet conversion in Oplopanax elatus,
      an endangered medicinal woody plant.
AB  - Oplopanax elatus is a medicinal plant on the verge of extinction because of
      overexploitation. In the present study, the effects of various factors on
      enhancing somatic embryogenesis and plantlet conversion were studied. Mature
      seeds were collected from a total of 13 plants from 4 mountains in South Korea,
      and the genetic distances were calculated to analyze the effect of genotype on
      somatic embryogenesis. Results of cluster analysis and the unweighted-pair-group
      method with arithmetic mean of 13 genotypes indicated the presence of 3 main
      groups. Both genotype and explant type affected the induction of somatic embryos
      (SEs). Sorak 2 and root were found to be the most suitable genotype and explant
      type, respectively, for SE induction in O. elatus. Among the different types of
      carbon sources tested, 5% sucrose induced the maximum number of SEs. The
      formation and development of SEs were significantly influenced by culture
      density; thus, 10 mg embryonic callus was found to be the most suitable for SE
      induction. The highest rates of germination and SE conversion were obtained in a
      germination medium containing 1.8 gelrite and 3.2 g.l(-1) agar. In addition, 80%
      of the plantlets that were transplanted into artificial soil acclimatized
      successfully. Thus, our results showed that the percentage survival of O. elatus
      during in vitro proliferation could be increased by optimizing to the somatic
      embryogenesis system. 

PMID- 24024110
TI  - Welcome to molecular metabolism!

PMID- 24024111
TI  - An inconvenient truth about obesity.

PMID- 24024112
TI  - Mapping leptin's link to reproduction.

PMID- 24024113
TI  - Our evolving understanding of the interaction between leptin and dopamine system
      to regulate ingestive behaviors.

PMID- 24024114
TI  - Neuroimaging the interaction of mind and metabolism in humans.
AB  - Hormonal and metabolic signals interact with neural circuits orchestrating
      behavior to guide food intake. Neuroimaging techniques such as functional
      magnetic resonance imaging (fMRI) enable the identification of where in the brain
      particular mental processes like desire, satiety and pleasure occur. Once these
      neural circuits are described it then becomes possible to determine how metabolic
      and hormonal signals can alter brain response to influence psychological states
      and decision-making processes to guide intake. Here, we provide an overview of
      the contributions of functional neuroimaging to the understanding of how
      subjective and neural responses to food and food cues interact with
      metabolic/hormonal factors. 

PMID- 24024115
TI  - Obesity and the gut microbiome: Striving for causality.
AB  - The gut microbiome has been proposed to play a causal role in obesity. Here, we
      review the historical context for this hypothesis, highlight recent key findings,
      and critically discuss issues central to further progress in the field, including
      the central epistemological problem for the field: how to define causality in the
      relationship between microbiota and obesity phenotypes. Definition of such will
      be critical for the field to move forward. 

PMID- 24024116
TI  - Uncovering the biology of FTO.
AB  - Genome-wide association studies have revealed that SNPs in the first intron of
      FTO (Fat mass and Obesity related) are robustly associated with body mass index
      and obesity. Subsequently, it has become clear that this association with body
      weight, and increasingly food intake, is replicable across multiple populations
      and different age groups. However, to date, no conclusive link has been made
      between the risk alleles and FTO expression or its physiological role. FTO
      deficiency leads to a complex phenotype including postnatal mortality and growth
      retardation, pointing to some fundamental developmental role. Yet, the weight of
      evidence from a number of animal models where FTO expression has been perturbed
      indicates some role for FTO in energy homoeostasis. In addition, emerging data
      points to a role for FTO in the sensing of nutrients. In this review, we explore
      the in vivo and in vitro evidence detailing FTO's different faces and discuss how
      these might link to the regulation of body weight. 

PMID- 24024119
TI  - Leptin action via LepR-b Tyr1077 contributes to the control of energy balance and
      female reproduction.
AB  - Leptin action in the brain signals the repletion of adipose energy stores,
      suppressing feeding and permitting energy expenditure on a variety of processes,
      including reproduction. Leptin binding to its receptor (LepR-b) promotes the
      tyrosine phosphorylation of three sites on LepR-b, each of which mediates
      distinct downstream signals. While the signals mediated by LepR-b Tyr1138 and
      Tyr985 control important aspects of energy homeostasis and LepR-b signal
      attenuation, respectively, the role of the remaining LepR-b phosphorylation site
      (Tyr1077) in leptin action has not been studied. To examine the function of
      Tyr1077, we generated a "knock-in" mouse model expressing LepR-b (F1077), which
      is mutant for LepR-b Tyr1077. Mice expressing LepR-b (F1077) demonstrate modestly
      increased body weight and adiposity. Furthermore, females display impairments in
      estrous cycling. Our results suggest that signaling by LepR-b Tyr1077 plays a
      modest role in the control of metabolism by leptin, and is an important link
      between body adiposity and the reproductive axis. 

PMID- 24024118
TI  - A guide for measurement of circulating metabolic hormones in rodents: Pitfalls
      during the pre-analytical phase.
AB  - Researchers analyse hormones to draw conclusions from changes in hormone
      concentrations observed under specific physiological conditions and to elucidate
      mechanisms underlying their biological variability. It is, however, frequently
      overlooked that also circumstances occurring after collection of biological
      samples can significantly affect the hormone concentrations measured, owing to
      analytical and pre-analytical variability. Whereas the awareness for such
      potential confounders is increasing in human laboratory medicine, there is
      sometimes limited consensus about the control of these factors in rodent studies.
      In this guide, we demonstrate how such factors can affect reliability and
      consequent interpretation of the data from immunoassay measurements of
      circulating metabolic hormones in rodent studies. We also compare the knowledge
      about such factors in rodent studies to recent recommendations established for
      biomarker studies in humans and give specific practical recommendations for the
      control of pre-analytical conditions in metabolic studies in rodents. 

PMID- 24024120
TI  - TOSO promotes beta-cell proliferation and protects from apoptosis.
AB  - Decreased beta-cell mass reflects a shift from quiescence/proliferation into
      apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major
      attempt to restore beta-cell mass and normoglycemia is to improve beta-cell
      survival. Here we show that switching off the Fas pathway using Fas apoptotic
      inhibitory protein (Faim/TOSO), which regulates apoptosis upstream of caspase 8,
      blocked beta-cell apoptosis and increased proliferation in human islets. TOSO was
      clearly expressed in pancreatic beta-cells and down-regulated in T2DM. TOSO
      expression correlated with beta-cell turnover; at conditions of improved
      survival, TOSO was induced. In contrast, TOSO downregulation induced beta-cell
      apoptosis. Although TOSO overexpression resulted in a 3-fold induction of
      proliferation, proliferating beta-cells showed a very limited capacity to undergo
      multiple rounds of replication. Our data suggest that TOSO is an important
      regulator of beta-cell turnover and switches beta-cell apoptosis into
      proliferation. 

PMID- 24024117
TI  - Emerging role of glial cells in the control of body weight.
AB  - Glia are the most abundant cell type in the brain and are indispensible for the
      normal execution of neuronal actions. They protect neurons from noxious insults
      and modulate synaptic transmission through affectation of synaptic inputs,
      release of glial transmitters and uptake of neurotransmitters from the synaptic
      cleft. They also transport nutrients and other circulating factors into the brain
      thus controlling the energy sources and signals reaching neurons. Moreover, glia
      express receptors for metabolic hormones, such as leptin and insulin, and can be
      activated in response to increased weight gain and dietary challenges. However,
      chronic glial activation can be detrimental to neurons, with hypothalamic
      astrocyte activation or gliosis suggested to be involved in the perpetuation of
      obesity and the onset of secondary complications. It is now accepted that glia
      may be a very important participant in metabolic control and a possible
      therapeutical target. Here we briefly review this rapidly advancing field. 

PMID- 24024121
TI  - Ghrelin-immunopositive hypothalamic neurons tie the circadian clock and visual
      system to the lateral hypothalamic arousal center.
AB  - Ghrelin, a circulating gut-hormone, has emerged as an important regulator of
      growth hormone release and appetite. Ghrelin-immunopositive neurons have also
      been identified in the hypothalamus with a unique anatomical distribution. Here,
      we report that ghrelin-labeled neurons receive direct synaptic input from the
      suprachiasmatic nucleus, the central circadian timekeeper of the brain, and
      lateral geniculate nucleus, a visual center, and project synaptically to the
      lateral hypothalamic orexin/hypocretin system, a region of the brain critical for
      arousal. Hypothalamic ghrelin mRNA oscillates in a circadian pattern peaking in
      the dark phase prior to the switch from arousal to sleep. Ghrelin inhibits the
      electrophysiological activity of identified orexin/hypocretin neurons in
      hypothalamic slices. These observations indicate that the hypothalamic neurons
      identified by ghrelin immunolabeling may be a key mediator of circadian and
      visual cues for the hypothalamic arousal system. 

PMID- 24024122
TI  - Leptin reduces food intake via a dopamine D2 receptor-dependent mechanism.
AB  - Food intake is generally accepted to be regulated by the melanocortin system,
      however recent data suggests that mesolimbic dopaminergic neurons also influence
      food intake. Whether dopamine signaling is crucial for the acute effect of leptin
      on feeding is unknown. Using pharmacological and genetic strategies, we tested
      the hypothesis that the acute inhibitory effect of leptin on food intake is
      partially mediated by dopamine. Dopamine D2 but not D1 receptor blockade
      attenuated the acute hypophagic effect of leptin in fasted mice. Additionally,
      mice lacking the D2R (D2R KO) exhibited an attenuated response to leptin.
      Conversely, dopamine receptor blockade had no effect on the acute hypophagic
      effect of melanocortin stimulation or the hyperphagic effect of ghrelin. These
      findings suggest that dopaminergic pathways do not constitute a normal part of
      melanocortin-dependent feeding regulation and that the dopaminergic
      neurocircuitry typically associated with regulation of hedonic feeding likely
      contributes to feeding regulation by leptin. 

PMID- 24024123
TI  - High calorie diet triggers hypothalamic angiopathy.
AB  - Obesity, type 2 diabetes, and related diseases represent major health threats to
      modern society. Related pathophysiology of impaired neuronal function in
      hypothalamic control centers regulating metabolism and body weight has been
      dissected extensively and recent studies have started focusing on potential roles
      of astrocytes and microglia. The hypothalamic vascular system, however, which
      maintains the microenvironment necessary for appropriate neuronal function, has
      been largely understudied. We recently discovered that high fat/high sucrose diet
      exposure leads to increased hypothalamic presence of immunoglobulin G (IgG1).
      Investigating this phenomenon further, we have discovered a significant increase
      in blood vessel length and density in the arcuate nucleus (ARC) of the
      hypothalamus in mice fed a high fat/high sucrose diet, compared to matched
      controls fed standard chow diet. We also found a clearly increased presence of
      alpha-smooth muscle actin immunoreactive vessels, which are rarely present in the
      ARC and indicate an increase in the formation of new arterial vessels. Along the
      blood brain barrier, an increase of degenerated endothelial cells are observed.
      Moreover, such hypothalamic angiogenesis was not limited to rodent models. We
      also found an increase in the number of arterioles of the infundibular nucleus
      (the human equivalent of the mouse ARC) in patients with type 2 diabetes,
      suggesting angiogenesis occurs in the human hypothalamus of diabetics. Our
      discovery reveals novel hypothalamic pathophysiology, which is reminiscent of
      diabetic retinopathy and suggests a potential functional involvement of the
      hypothalamic vasculature in the later stage pathogenesis of metabolic syndrome. 

PMID- 24024124
TI  - Fgf signaling in adipocytes as a target for metabolic diseases.

PMID- 24024125
TI  - Not so hot: Optimal housing temperatures for mice to mimic the thermal
      environment of humans.
AB  - It has been argued that mice should be housed at 30  degrees C to best mimic the
      thermal conditions experienced by humans, and that the current practice of
      housing mice at 20-22  degrees C impairs the suitability of mice as a model for
      human physiology and disease. In the current paper we challenge this notion.
      First, we show that humans routinely occupy environments about 3  degrees C below
      their lower critical temperature (T lc), which when lightly clothed is about 23 
      degrees C. Second, we review the data for the T lc of mice. Mouse T lc is
      dependent on body weight and about 26-28  degrees C for adult mice weighing >25
      g. The equivalent temperature to that normally experienced by humans for most
      single housed adult mice is therefore 23-25  degrees C. Group housing or
      providing the mice with bedding and nesting material might lower this to about 20
      22  degrees C, close to current standard practice. 

PMID- 24024126
TI  - High-fat diet consumption during pregnancy and the early post-natal period leads
      to decreased alpha cell plasticity in the nonhuman primate.
AB  - We investigated the impact of poor maternal nutrition and metabolic health on the
      development of islets of the nonhuman primate (NHP). Interestingly, fetal
      offspring of high fat diet (HFD) fed animals had normal total islet and beta cell
      mass; however, there was a significant reduction in alpha cell mass, and
      decreased expression of transcription factors involved in alpha cell
      differentiation. In juvenile animals all offspring maintained on a HFD during the
      postweaning period demonstrated increases in total islet mass, however, the
      control offspring displaying increased islet number, and HFD offspring displayed
      increased islet size. Finally, while control offspring had increases in alpha and
      beta cells, the HFD offspring had increases only in beta cell number. These
      studies indicate that consumption of a HFD diet during pregnancy in the NHP,
      independent of maternal metabolic health, causes long-term abnormalities in alpha
      cell plasticity that may contribute to chronic disease susceptibility. 

PMID- 24024127
TI  - The breadth of FGF21's metabolic actions are governed by FGFR1 in adipose tissue.
AB  - FGF21 is a multifunctional metabolic regulator. The co-factor betaKlotho (KLB)
      allows FGF21 to signal via FGF receptors. Given the widespread nature of FGFR
      expression and KLB presence in several organs, it remains unclear which
      tissue/FGFR isoform determine FGF21 action. Here we show that deletion of FGFR1
      in fat (FR1KO) leads to a complete ablation of FGF21 stimulated transcriptional
      activity in this tissue. Furthermore, FR1KO mice showed no FGF21-mediated
      lowering of plasma glucose, insulin and triglycerides, altered serum levels of
      adipokines, no increase in energy expenditure, but preserved reductions in
      serum/liver FFAs as compared to wild type mice. Of importance, the anti-glycaemic
      actions of FGF19 were fully evident in FR1KO mice implying that FGF19 functions
      in a FGFR1/adipose independent manner. Taken together, our findings reveal the
      existence of an adipose FGFR1 driven axis of cross-tissue communication which
      defines several aspects of FGF21 biology and delineates mechanistic distinctions
      between FGF21 and FGF19. 

PMID- 24024128
TI  - The human lipodystrophy protein seipin is an ER membrane adaptor for the
      adipogenic PA phosphatase lipin 1.
AB  - Disruption of the gene BSCL2 causes a severe, generalised lipodystrophy,
      demonstrating the critical role of its protein product, seipin, in human adipose
      tissue development. Seipin is essential for adipocyte differentiation, whilst the
      study of seipin in non-adipose cells has suggested a role in lipid droplet
      formation. However, its precise molecular function remains poorly understood.
      Here we demonstrate that seipin can inducibly bind lipin 1, a phosphatidic acid
      (PA) phosphatase important for lipid synthesis and adipogenesis. Knockdown of
      seipin during early adipogenesis decreases the association of lipin 1 with
      membranes and increases the accumulation of its substrate PA. Conversely, PA
      levels are reduced in differentiating cells by overexpression of wild-type seipin
      but not by expression of a mutated seipin that is unable to bind lipin 1.
      Together our data identify lipin as the first example of a seipin-interacting
      protein and reveals a novel molecular function for seipin in developing
      adipocytes. 

PMID- 24024129
TI  - The role of sodium-coupled glucose co-transporter 3 in the satiety effect of
      portal glucose sensing.
AB  - Portal vein glucose sensors detect variations in glycemia to induce a nervous
      signal that influences food intake and glucose homeostasis. Previous experiments
      using high infusions of glucose suggested a metabolic sensing involving glucose
      transporter 2 (GLUT2). Here we evaluated the afferent route for the signal and
      candidate molecules for detecting low glucose fluxes. Common hepatic branch
      vagotomy did not abolish the anorectic effect of portal glucose, indicating
      dorsal transmission. GLUT2-null mice reduced their food intake in response to
      portal glucose signal initiated by protein-enriched diet. A similar response of
      Trpm5-null mice and portal infusions of sweeteners also excluded sugar taste
      receptors. Conversely, infusions of alpha-methylglucose, but not 3-O
      methylglucose, decreased food intake, while phlorizin prevented the effect of
      glucose. This suggested sensing through SGLT3, which was expressed in the portal
      area. From these results we propose a finely tuned dual mechanism for portal
      glucose sensing that responds to different physiological conditions. 

PMID- 24024130
TI  - You are what you eat-Do not blame your mother.

PMID- 24024131
TI  - Ghrelin regulates hypothalamic prolyl carboxypeptidase expression in mice.
AB  - Hypothalamic Prolyl carboxypeptidase (PRCP) plays a role in the regulation of
      energy metabolism by inactivating hypothalamic alpha-melanocyte stimulating
      hormone (alpha-MSH) levels and thus affecting melanocortin signaling. Alpha-MSH
      production is highly regulated both at transcriptional and posttranslational
      levels. Here we show that fasting induces a hypothalamic-specific up-regulation
      of Prcp mRNA and protein levels. Since fasting is characterized by elevated
      circulating ghrelin levels, we tested the effect of peripheral and central
      administration of ghrelin, and found that ghrelin increases hypothalamic Prcp
      mRNA expression. No changes in Prcp mRNA levels were detected in ghrelin knockout
      mice compared to their controls. Finally, ghrelin effect on PRCP expression was
      ghrelin receptor-mediated. Altogether our data show that ghrelin is a key
      regulator of hypothalamic PRCP expression, and up-regulation of PRCP by ghrelin
      may be an additional mechanism to decrease melanocortin signaling. 

PMID- 24024132
TI  - Nitrosative stress and redox-cycling agents synergize to cause mitochondrial
      dysfunction and cell death in endothelial cells.
AB  - Nitric oxide production by the endothelium is required for normal vascular
      homeostasis; however, in conditions of oxidative stress, interactions of nitric
      oxide with reactive oxygen species (ROS) are thought to underlie endothelial
      dysfunction. Beyond canonical nitric oxide signaling pathways, nitric oxide
      production results in the post-translational modification of protein thiols,
      termed S-nitrosation. The potential interplay between S-nitrosation and ROS
      remains poorly understood and is the focus of the current study. The effects of
      the S-nitrosating agent S-nitrosocysteine (CysNO) in combination with redox
      cycling agents was examined in bovine aortic endothelial cells (BAEC). CysNO
      significantly impairs mitochondrial function and depletes the NADH/NAD(+) pool;
      however, these changes do not result in cell death. When faced with the
      additional stressor of a redox-cycling agent used to generate ROS, further loss
      of NAD(+) occurs, and cellular ATP pools are depleted. Cellular S-nitrosothiols
      also accumulate, and cell death is triggered. These data demonstrate that CysNO
      sensitizes endothelial cells to redox-cycling agent-dependent mitochondrial
      dysfunction and cell death and identify attenuated degradation of S-nitrosothiols
      as one potential mechanism for the enhanced cytotoxicity. 

PMID- 24024133
TI  - Histone modifications in senescence-associated resistance to apoptosis by
      oxidative stress.
AB  - Aging and age-related diseases are associated with cellular senescence that
      results in variable apoptosis susceptibility to oxidative stress. Although
      fibroblast senescence has been associated with apoptosis resistance, mechanisms
      for this have not been well defined. In this report, we studied epigenetic
      mechanisms involving histone modifications that confer apoptosis resistance to
      senescent human diploid fibroblasts (HDFs). HDFs that undergo replicative
      senescence display typical morphological features, express senescence-associated
      beta-galactosidase, and increased levels of the tumor suppressor genes, p16, p21,
      and caveolin-1. Senescent HDFs are more resistant to oxidative stress (exogenous
      H2O2)-induced apoptosis in comparison to non-senescent (control) HDFs; this is
      associated with constitutively high levels of the anti-apoptotic gene, Bcl-2, and
      low expression of the pro-apoptotic gene, Bax. Cellular senescence is
      characterized by global increases in H4K20 trimethylation and decreases in H4K16
      acetylation in association with increased activity of Suv420h2 histone
      methyltransferase (which targets H4K20), decreased activity of the histone
      acetyltransferase, Mof (which targets H4K16), as well as decreased total histone
      acetyltransferase activity. In contrast to Bax gene, chromatin
      immunoprecipitation studies demonstrate marked enrichment of the Bcl-2 gene with
      H4K16Ac, and depletion with H4K20Me3, predicting active transcription of this
      gene in senescent HDFs. These data indicate that both global and locus-specific
      histone modifications of chromatin regulate altered Bcl-2:Bax gene expression in
      senescent fibroblasts, contributing to its apoptosis-resistant phenotype. 

PMID- 24024134
TI  - Launch of Redox Biology: A new venue for studies in translational, basic and
      applied research in the fields of antioxidants, cell signaling and redox
      therapeutics.

PMID- 24024135
TI  - Hydrogen peroxide induce modifications of human extracellular superoxide
      dismutase that results in enzyme inhibition.
AB  - Superoxide dismutase (EC-SOD) controls the level of superoxide in the
      extracellular space by catalyzing the dismutation of superoxide into hydrogen
      peroxide and molecular oxygen. In addition, the enzyme reacts with hydrogen
      peroxide in a peroxidase reaction which is known to disrupt enzymatic activity.
      Here, we show that the peroxidase reaction supports a site-specific bond
      cleavage. Analyses by peptide mapping and mass spectrometry shows that oxidation
      of Pro112 supports the cleavage of the Pro112-His113 peptide bond. Substitution
      of Ala for Pro112 did not inhibit fragmentation, indicating that the oxidative
      fragmentation at this position is dictated by spatial organization and not by
      side-chain specificity. The major part of EC-SOD inhibited by the peroxidase
      reaction was not fragmented but found to encompass oxidations of histidine
      residues involved in the coordination of copper (His98 and His163). These
      oxidations are likely to support the dissociation of copper from the active site
      and thus loss of enzymatic activity. Homologous modifications have also been
      described for the intracellular isozyme, Cu/Zn-SOD, reflecting the almost
      identical structures of the active site within these enzymes. We speculate that
      the inactivation of EC-SOD by peroxidase activity plays a role in regulating SOD
      activity in vivo, as even low levels of superoxide will allow for the peroxidase
      reaction to occur. 

PMID- 24024136
TI  - The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer.
AB  - The Keap1-Nrf2 pathway is the major regulator of cytoprotective responses to
      oxidative and electrophilic stress. Although cell signaling pathways triggered by
      the transcription factor Nrf2 prevent cancer initiation and progression in normal
      and premalignant tissues, in fully malignant cells Nrf2 activity provides growth
      advantage by increasing cancer chemoresistance and enhancing tumor cell growth.
      In this graphical review, we provide an overview of the Keap1-Nrf2 pathway and
      its dysregulation in cancer cells. We also briefly summarize the consequences of
      constitutive Nrf2 activation in cancer cells and how this can be exploited in
      cancer gene therapy. 

PMID- 24024137
TI  - Oxidized lipids activate autophagy in a JNK-dependent manner by stimulating the
      endoplasmic reticulum stress response.
AB  - Excessive production of unsaturated aldehydes from oxidized lipoproteins and
      membrane lipids is a characteristic feature of cardiovascular disease. Our
      previous studies show that unsaturated lipid peroxidation-derived aldehydes such
      as 4-hydroxy-trans-2-nonenal (HNE) promote autophagy in rat aortic smooth muscle
      cells (RASMC). In this study, we examined the mechanism by which HNE induces
      autophagy. Exposure of RASMC to HNE led to the modification of several proteins,
      most of which were identified by mass spectrometry and confocal microscopy to be
      localized to the endoplasmic reticulum (ER). HNE stimulated the phosphorylation
      of PKR-like ER kinase and eukaryotic initiation factor 2alpha and increased heme
      oxygenase-1 (HO-1) abundance. HNE treatment also increased LC3-II formation and
      the phosphorylation of JNK and p38. Pharmacological inhibition of JNK, but not
      p38, prevented HNE-induced HO-1 expression and LC3-II formation. Inhibition of
      JNK increased cell death in HNE-treated cells. Pretreatment with the chemical
      chaperone phenylbutryic acid prevented LC3-II formation as well as JNK
      phosphorylation and HO-1 induction. Taken together, these data suggest that
      autophagic responses triggered by unsaturated aldehydes could be attributed, in
      part, to ER stress, which stimulates autophagy by a JNK-dependent mechanism and
      promotes cell survival during oxidative stress. 

PMID- 24024138
TI  - Is methemoglobin an inert bystander, biomarker or a mediator of oxidative stress-
      The example of anemia?
AB  - Acute anemia increases the risk for perioperative morbidity and mortality in
      critically ill patients who experience blood loss and fluid resuscitation
      (hemodilution). Animal models of acute anemia suggest that neuronal nitric oxide
      synthase (nNOS)-derived nitric oxide (NO) is adaptive and protects against anemia
      induced mortality. During acute anemia, we have observed a small but consistent
      increase in methemoglobin (MetHb) levels that is inversely proportional to the
      acute reduction in Hb observed during hemodilution in animals and humans. We
      hypothesize that this increase in MetHb may be a biomarker of anemia-induced
      tissue hypoxia. The increase in MetHb may occur by at least two mechanisms: (1)
      direct hemoglobin oxidation by increased nNOS-derived NO within the perivascular
      tissue and (2) by increased deoxyhemoglobin (DeoxyHb) nitrite reductase activity
      within the vascular compartment. Both mechanisms reflect a potential increase in
      NO signaling from the tissue and vascular compartments during anemia. These
      responses are thought to be adaptive; as deletion of nNOS results in increased
      mortality in a model of acute anemia. Finally, it is possible that prolonged
      activation of these mechanisms may lead to maladaptive changes in redox
      signaling. We hypothesize, increased MetHb in the vascular compartment during
      acute anemia may reflect activation of adaptive mechanisms which augment NO
      signaling. Understanding the link between anemia, MetHb and its treatments
      (transfusion of stored blood) may help us to develop novel treatment strategies
      to reduce the risk of anemia-induced morbidity and mortality. 

PMID- 24024139
TI  - Differential activation of catalase expression and activity by PPAR agonists:
      implications for astrocyte protection in anti-glioma therapy.
AB  - Glioma survival is dismal, in part, due to an imbalance in antioxidant expression
      and activity. Peroxisome proliferator-activated receptor (PPAR) agonists have
      antineoplastic properties which present new redox-dependent targets for glioma
      anticancer therapies. Herein, we demonstrate that treatment of primary cultures
      of normal rat astrocytes with PPAR agonists increased the expression of catalase
      mRNA protein, and enzymatic activity. In contrast, these same agonists had no
      effect on catalase expression and activity in malignant rat glioma cells. The
      increase in steady-state catalase mRNA observed in normal rat astrocytes was due,
      in part, to de novo mRNA synthesis as opposed to increased catalase mRNA
      stability. Moreover, pioglitazone-mediated induction of catalase activity in
      normal rat astrocytes was completely blocked by transfection with a PPARgamma
      dominant negative plasmid. These data suggest that defects in PPAR-mediated
      signaling and gene expression may represent a block to normal catalase expression
      and induction in malignant glioma. The ability of PPAR agonists to differentially
      increase catalase expression and activity in normal astrocytes but not glioma
      cells suggests that these compounds might represent novel adjuvant therapeutic
      agents for the treatment of gliomas. 

PMID- 24024141
TI  - Redox-derived damage-associated molecular patterns: Ligand function of lipid
      peroxidation adducts.
AB  - Endogenous electrophiles, such as alpha,beta-unsaturated aldehydes and ketones
      generated during lipid peroxidation, exhibit a facile reactivity with proteins,
      generating a variety of intra and intermolecular covalent adducts. It has been
      postulated that these host-derived, modified proteins with electrophiles, which
      constitute the products of diverse classes of oxidative reactions, represent
      damage-associated molecular patterns (DAMPs). The DAMPs, that occur in vivo, can
      be a ligand of multiple proteins, which in turn, may lead to the profound innate
      and adaptive immune responses and mediate homeostatic functions consequent to
      inflammation and cell death. 

PMID- 24024140
TI  - Oxidative modification of lipoic acid by HNE in Alzheimer disease brain.
AB  - Alzheimer disease (AD) is an age-related neurodegenerative disease characterized
      by the presence of three pathological hallmarks: synapse loss, extracellular
      senile plaques (SP) and intracellular neurofibrillary tangles (NFTs). The major
      component of SP is amyloid beta-peptide (Abeta), which has been shown to induce
      oxidative stress. The AD brain shows increased levels of lipid peroxidation
      products, including 4-hydroxy-2-nonenal (HNE). HNE can react covalently with Cys,
      His, or Lys residues on proteins, altering structure and function of the latter.
      In the present study we measured the levels of the HNE-modified lipoic acid in
      brain of subjects with AD and age-matched controls. Lipoic acid is a key co
      factor for a number of proteins including pyruvate dehydrogenase and alpha
      ketoglutarate dehydrogenase, key complexes for cellular energetics. We observed a
      significant decrease in the levels of HNE-lipoic acid in the AD brain compared to
      that of age-matched controls. To investigate this phenomenon further, the levels
      and activity of lipoamide dehydrogenase (LADH) were measured in AD and control
      brains. Additionally, LADH activities were measured after in-vitro HNE-treatment
      to mice brains. Both LADH levels and activities were found to be significantly
      reduced in AD brain compared to age-matched control. HNE-treatment also reduced
      the LADH activity in mice brain. These data are consistent with a two-hit
      hypothesis of AD: oxidative stress leads to lipid peroxidation that, in turn,
      causes oxidative dysfunction of key energy-related complexes in mitochondria,
      triggering neurodegeneration. This study is consonant with the notion that lipoic
      acid supplementation could be a potential treatment for the observed loss of
      cellular energetics in AD and potentiate the antioxidant defense system to
      prevent or delay the oxidative stress in and progression of this devastating
      dementing disorder. 

PMID- 24024142
TI  - Attenuation of lipopolysaccharide (LPS)-induced cytotoxicity by tocopherols and
      tocotrienols.
AB  - Lipopolysaccharide (LPS) induces host inflammatory responses and tissue injury
      and has been implicated in the pathogenesis of various age-related diseases such
      as acute respiratory distress syndrome, vascular diseases, and periodontal
      disease. Antioxidants, particularly vitamin E, have been shown to suppress
      oxidative stress induced by LPS, but the previous studies with different vitamin
      E isoforms gave inconsistent results. In the present study, the protective
      effects of alpha- and gamma-tocopherols and alpha- and gamma-tocotrienols on the
      oxidative stress induced by LPS against human lung carcinoma A549 cells were
      studied. They suppressed intracellular reactive oxygen formation, lipid
      peroxidation, induction of inflammatory mediator cytokines, and cell death.
      Tocopherols were incorporated into cultured cells much slower than tocotrienols
      but could suppress LPS-induced oxidative stress at much lower intracellular
      concentration than tocotrienols. Considering the bioavailability, it was
      concluded that alpha-tocopherol may exhibit the highest protective capacity among
      the vitamin E isoforms against LPS-induced oxidative stress. 

PMID- 24024143
TI  - Arsenite-induced stress signaling: modulation of the phosphoinositide 3'
      kinase/Akt/FoxO signaling cascade.
AB  - FoxO transcription factors and their regulators in the phosphoinositide 3'-kinase
      (PI3K)/Akt signaling pathway play an important role in the control of cellular
      processes involved in carcinogenesis, such as proliferation and apoptosis. We
      have previously demonstrated that physiologically relevant heavy metal ions, such
      as copper or zinc ions, can stimulate this pathway, triggering phosphorylation
      and nuclear export of FoxO transcription factors. The present study aims at
      investigating the effect of arsenite on FoxO transcription factors and the role
      of PI3K/Akt signaling therein. Exposure of HaCaT human keratinocytes to arsenite
      resulted in a distinct decrease of glutathione levels only at cytotoxic
      concentrations. In contrast, a strong phosphorylation of FoxO1a/FoxO3a and Akt
      was observed at subcytotoxic concentrations of arsenite in HaCaT human
      keratinocytes. A time- and concentration-dependent increase in phosphorylation of
      FoxO1a and FoxO3a at sites known to be phosphorylated by Akt as well as
      phosphorylation of Akt at Ser-473 was detected. These phosphorylations were
      blunted in the presence of wortmannin, pointing to the involvement of PI3K. 

PMID- 24024144
TI  - Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of
      cellular redox balance.
AB  - JS-K is a nitric oxide (NO)-releasing prodrug of the O (2)-arylated
      diazeniumdiolate family that has demonstrated pronounced cytotoxicity and
      antitumor properties in a variety of cancer models both in vitro and in vivo. The
      current study of the metabolic actions of JS-K was undertaken to investigate
      mechanisms of its cytotoxicity. Consistent with model chemical reactions, the
      activating step in the metabolism of JS-K in the cell is the dearylation of the
      diazeniumdiolate by glutathione (GSH) via a nucleophilic aromatic substitution
      reaction. The resulting product (CEP/NO anion) spontaneously hydrolyzes,
      releasing two equivalents of NO. The GSH/GSSG redox couple is considered to be
      the major redox buffer of the cell, helping maintain a reducing environment under
      basal conditions. We have quantified the effects of JS-K on cellular GSH content,
      and show that JS-K markedly depletes GSH, due to JS-K's rapid uptake and
      cascading release of NO and reactive nitrogen species. The depletion of GSH
      results in alterations in the redox potential of the cellular environment,
      initiating MAPK stress signaling pathways, and inducing apoptosis. Microarray
      analysis confirmed signaling gene changes at the transcriptional level and
      revealed alteration in the expression of several genes crucial for maintenance of
      cellular redox homeostasis, as well as cell proliferation and survival, including
      MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing
      agent N-acetylcysteine prevented the signaling events that lead to apoptosis.
      These data indicate that multiplicative depletion of the reduced glutathione pool
      and deregulation of intracellular redox balance are important initial steps in
      the mechanism of JS-K's cytotoxic action. 

PMID- 24024145
TI  - Oxysterols in the pathogenesis of major chronic diseases.
AB  - Pathological accumulation of 27-carbon intermediates or end-products of
      cholesterol metabolism, named oxysterols, may contribute to the onset and
      especially to the development of major chronic diseases in which inflammation,
      but also oxidative damage and to a certain extent cell death, are hallmarks and
      primary mechanisms of progression. Indeed, certain oxysterols exercise strong pro
      oxidant and pro-inflammatory effects at concentrations detectable in the lesions
      typical of atherosclerosis, neurodegenerative diseases, inflammatory bowel
      diseases, age-related macular degeneration, and other pathological conditions
      characterized by altered cholesterol uptake and/or metabolism. 

PMID- 24024146
TI  - Lipofuscin: formation, effects and role of macroautophagy.
AB  - Oxidative stress plays a crucial role in the development of the aging process and
      age dependent diseases. Both are closely connected to disturbances of
      proteostasis by protein oxidation and an impairment of the proteasomal system.
      The final consequence is the accumulation of highly cross-linked undegradable
      aggregates such as lipofuscin. These aggregates of damaged proteins are
      detrimental to normal cell functions. Here we provide an overview about effect of
      these aggregates on the proteasomal system, followed by transcription factor
      activation and loss of cell viability. Furthermore, findings on the mechanism of
      radical genesis, proteasomal inhibition and the required components of lipofuscin
      formation were resumed. 

PMID- 24024147
TI  - The lipid peroxidation product 4-hydroxy-2-nonenal: Advances in chemistry and
      analysis.
AB  - 4-Hydroxy-2-nonenal (HNE) is one of the most studied products of phospholipid
      peroxidation, owing to its reactivity and cytotoxicity. It can be formed by
      several radical-dependent oxidative routes involving the formation of
      hydroperoxides, alkoxyl radicals, epoxides, and fatty acyl cross-linking
      reactions. Cleavage of the oxidized fatty acyl chain results in formation of HNE
      from the methyl end, and 9-oxo-nonanoic acid from the carboxylate or esterified
      end of the chain, although many other products are also possible. HNE can be
      metabolized in tissues by a variety of pathways, leading to detoxification and
      excretion. HNE-adducts to proteins have been detected in inflammatory situations
      such as atherosclerotic lesions using polyclonal and monoclonal antibodies, which
      have also been applied in ELISAs and western blotting. However, in order to
      identify the proteins modified and the exact sites and nature of the
      modifications, mass spectrometry approaches are required. Combinations of
      enrichment strategies with targetted mass spectrometry routines such as neutral
      loss scanning are now facilitating detection of HNE-modified proteins in complex
      biological samples. This is important for characterizing the interactions of HNE
      with redox sensitive cell signalling proteins and understanding how it may
      modulate their activities either physiologically or in disease. 

PMID- 24024148
TI  - Characterizing low dose and dose rate effects in rodent and human neural stem
      cells exposed to proton and gamma irradiation.
AB  - Past work has shown that exposure to gamma rays and protons elicit a persistent
      oxidative stress in rodent and human neural stem cells (hNSCs). We have now
      adapted these studies to more realistic exposure scenarios in space, using lower
      doses and dose rates of these radiation modalities, to further elucidate the role
      of radiation-induced oxidative stress in these cells. Rodent neural stem and
      precursor cells grown as neurospheres and human neural stem cells grown as
      monolayers were subjected to acute and multi-dosing paradigms at differing dose
      rates and analyzed for changes in reactive oxygen species (ROS), reactive
      nitrogen species (RNS), nitric oxide and superoxide for 2 days after irradiation.
      While acute exposures led to significant changes in both cell types, hNSCs in
      particular, exhibited marked and significant elevations in radiation-induced
      oxidative stress. Elevated oxidative stress was more significant in hNSCs as
      opposed to their rodent counterparts, and hNSCs were significantly more sensitive
      to low dose exposures in terms of survival. Combinations of protons and gamma
      rays delivered as lower priming or higher challenge doses elicited radioadaptive
      changes that were associated with improved survival, but in general, only under
      conditions where the levels of reactive species were suppressed compared to cells
      irradiated acutely. Protective radioadaptive effects on survival were eliminated
      in the presence of the antioxidant N-acetylcysteine, suggesting further that
      radiation-induced oxidative stress could activate pro-survival signaling pathways
      that were sensitive to redox state. Data corroborates much of our past work and
      shows that low dose and dose rate exposures elicit significant changes in
      oxidative stress that have functional consequences on survival. 

PMID- 24024149
TI  - Imbalance of mitochondrial-nuclear cross talk in isocyanate mediated pulmonary
      endothelial cell dysfunction.
AB  - Mechanistic investigations coupled with epidemiology, case-control, cohort and
      observational studies have increasingly linked isocyanate exposure (both chronic
      and acute) with pulmonary morbidity and mortality. Though ascribed for impairment
      in endothelial cell function, molecular mechanisms of these significant adverse
      pulmonary outcomes remains poorly understood. As preliminary studies conducted in
      past have failed to demonstrate a cause-effect relationship between isocyanate
      toxicity and compromised pulmonary endothelial cell function, we hypothesized
      that direct exposure to isocyanate may disrupt endothelial structural lining,
      resulting in cellular damage. Based on this premise, we comprehensively evaluated
      the molecular repercussions of methyl isocyanate (MIC) exposure on human
      pulmonary arterial endothelial cells (HPAE-26). We examined MIC-induced
      mitochondrial oxidative stress, pro-inflammatory cytokine response, oxidative DNA
      damage response and apoptotic index. Our results demonstrate that exposure to
      MIC, augment mitochondrial reactive oxygen species production, depletion in
      antioxidant defense enzymes, elevated pro-inflammatory cytokine response and
      induced endothelial cell apoptosis via affecting the balance of mitochondrial
      nuclear cross talk. We herein delineate the first and direct molecular cascade of
      isocyanate-induced pulmonary endothelial cell dysfunction. The results of our
      study might portray a connective link between associated respiratory morbidities
      with isocyanate exposure, and indeed facilitate to discern the exposure-phenotype
      relationship in observed deficits of pulmonary endothelial cell function.
      Further, understanding of inter- and intra-cellular signaling pathways involved
      in isocyanate-induced endothelial damage would not only aid in biomarker
      identification but also provide potential new avenues to target specific
      therapeutic interventions. 

PMID- 24024151
TI  - The proteasome and the degradation of oxidized proteins: Part I-structure of
      proteasomes.
AB  - The main machinery responsible for cellular protein maintenance is the ubiquitin
      proteasomal system, with its core particle the 20S proteasome. The main task of
      the system is a fast and efficient degradation of proteins not needed anymore in
      cellular metabolism. For this aim a complex system of regulators evolved,
      modifying the function of the 20S core proteasome. Here we summarize shortly the
      structure of the 20S proteasome as well as its associated regulator proteins. 

PMID- 24024150
TI  - Maintenance of mitochondrial genomic integrity in the absence of manganese
      superoxide dismutase in mouse liver hepatocytes.
AB  - Manganese superoxide dismutase, encoded by the Sod2 gene, is a ubiquitously
      expressed mitochondrial antioxidant enzyme that is essential for mammalian life.
      Mice born with constitutive genetic knockout of Sod2 do not survive the neonatal
      stage, which renders the longitudinal study of the biochemical and metabolic
      effects of Sod2 loss difficult. However, multiple studies have demonstrated that
      tissue-specific knockout of Sod2 in murine liver yields no observable gross
      pathology or injury to the mouse. We hypothesized that Sod2 loss may have sub
      pathologic effects on liver biology, including the acquisition of reactive oxygen
      species-mediated mitochondrial DNA mutations. To evaluate this, we established
      and verified a hepatocyte-specific knockout of Sod2 in C57/B6 mice using Cre-LoxP
      recombination technology. We utilized deep sequencing to identify possible
      mutations in Sod2 (-/-) mitochondrial DNA as compared to wt, and both RT-PCR and
      traditional biochemical assays to evaluate baseline differences in redox
      sensitive pathways in Sod2 (-/-) hepatocytes. Surprisingly, no mutations in Sod2
      (-/-) mitochondrial DNA were detected despite measurable increases in
      dihydroethidium staining in situ and concomitant decreases in complex II activity
      indicative of elevated superoxide in the Sod2 (-/-) hepatocytes. In contrast,
      numerous compensatory alterations in gene expression were identified that suggest
      hepatocytes have a remarkable capacity to adapt and overcome the loss of Sod2
      through transcriptional means. Taken together, these results suggest that murine
      hepatocytes have a large reserve capacity to cope with the presence of additional
      mitochondrial reactive oxygen species. 

PMID- 24024152
TI  - Competition of nuclear factor-erythroid 2 factors related transcription factor
      isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction.
AB  - Although the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2)
      regulated expression of multiple antioxidant and cytoprotective genes through the
      electrophile responsive element (EpRE) is well established, interaction of
      Nrf2/EpRE with Nrf1, a closely-related transcription factor, is less well
      understood. Due to either proteolysis or alternative translation, Nrf1 has been
      found as proteins of varying size, p120, p95, and p65, which have been described
      as either activators of EpRE or competitive inhibitors of Nrf2. We investigated
      the effect of Nrf1 on EpRE-regulated gene expression using the catalytic and
      modifier subunits of glutamate cysteine ligase (GCLC and GCLM) as models and
      explored the potential role of Nrf1 in altering their expression in aging and
      upon chronic exposure to airborne nano-sized particulate matter (nPM). Nrf1
      knockout resulted in the increased expression of GCLC and GCLM in human bronchial
      epithelial (HBE1) cells. Overexpression Nrf2 in combination with either p120 or
      p65 diminished or failed to further increase the GCLC- and GLCM-EpRE luciferase
      activity. All known forms of Nrf1 protein, remained unchanged in the lungs of
      mice with age or in response to nPM. Our study shows that Nrf1 could inhibit EpRE
      activity in vitro, whereas the precise role of Nrf1 in vivo requires further
      investigations. We conclude that Nrf1 may not be directly responsible for the
      loss of Nrf2-dependent inducibility of antioxidant and cytoprotective genes
      observed in aged animals. 

PMID- 24024154
TI  - Oxygen dependence of nitric oxide-mediated signaling.
AB  - Nitric oxide (*NO) is a biologically important short-lived free radical signaling
      molecule. Both the enzymatic synthesis and the predominant forms of cellular
      metabolism of *NO are oxygen-dependent. For these reasons, changes in local
      oxygen concentrations can have a profound influence on steady-state *NO
      concentrations. Many proteins are regulated by *NO in a concentration-dependent
      manner, but their responses are elicited at different thresholds. Using soluble
      guanylyl cyclase (sGC) and p53 as model *NO-sensitive proteins, we demonstrate
      that their concentration-dependent responses to *NO are a function of the O2
      concentration. p53 requires relatively high steady-state *NO concentrations (>600
      nM) to induce its phosphorylation (P-ser-15), whereas sGC responds to low *NO
      concentrations (<100 nM). At a constant rate of *NO production (liberation from
      *NO-donors), decreasing the O2 concentration (1%) lowers the rate of *NO
      metabolism. This raises steady-state *NO concentrations and allows p53 activation
      at lower doses of the *NO donor. Enzymatic *NO production, however, requires O2
      as a substrate such that decreasing the O2 concentration below the K m for O2 for
      nitric oxide synthase (NOS) will decrease the production of *NO. We demonstrate
      that the amount of *NO produced by RAW 264.7 macrophages is a function of the O2
      concentration. Differences in rates of *NO production and *NO metabolism result
      in differential sGC activation that is not linear with respect to O2. There is an
      optimal O2 concentration (~5-8%) where a balance between the synthesis and
      metabolism of *NO is established such that both the *NO concentration and sGC
      activation are maximal. 

PMID- 24024155
TI  - Redox-control of the alarmin, Interleukin-1alpha.
AB  - The pro-inflammatory cytokine Interleukin-1alpha (IL-1alpha) has recently emerged
      as a susceptibility marker for a wide array of inflammatory diseases associated
      with oxidative stress including Alzheimer's, arthritis, atherosclerosis, diabetes
      and cancer. In the present study, we establish that expression and nuclear
      localization of IL-1alpha are redox-dependent. Shifts in steady-state H2O2
      concentrations (SS-[H2O2]) resulting from enforced expression of manganese
      superoxide dismutase (SOD2) drive IL-1alpha mRNA and protein expression. The
      redox-dependent expression of IL-1alpha is accompanied by its increased nuclear
      localization. Both IL-1alpha expression and its nuclear residency are abrogated
      by catalase co-expression. Sub-lethal doses of H2O2 also cause IL-1alpha nuclear
      localization. Mutagenesis revealed IL-1alpha nuclear localization does not
      involve oxidation of cysteines within its N terminal domain. Inhibition of the
      processing enzyme calpain prevents IL-1alpha nuclear localization even in the
      presence of H2O2. H2O2 treatment caused extracellular Ca(2+) influx suggesting
      oxidants may influence calpain activity indirectly through extracellular Ca(2+)
      mobilization. Functionally, as a result of its nuclear activity, IL-1alpha
      overexpression promotes NF-kB activity, but also interacts with the histone
      acetyl transferase (HAT) p300. Together, these findings demonstrate a mechanism
      by which oxidants impact inflammation through IL-1alpha and suggest that
      antioxidant-based therapies may prove useful in limiting inflammatory disease
      progression. 

PMID- 24024156
TI  - Measurement of HNE-protein adducts in human plasma and serum by ELISA-Comparison
      of two primary antibodies.
AB  - There is increasing evidence that non-enzymatic post-translational protein
      modifications might play key roles in various diseases. These protein
      modifications can be caused by free radicals generated during oxidative stress or
      by their products generated during lipid peroxidation. 4-Hydroxynonenal (HNE), a
      major biomarker of oxidative stress and lipid peroxidation, has been recognized
      as important molecule in pathology as well as in physiology of living organisms.
      Therefore, its detection and quantification can be considered as valuable tool
      for evaluating various pathophysiological conditions. The HNE-protein adduct
      ELISA is a method to detect HNE bound to proteins, which is considered as the
      most likely form of HNE occurrence in living systems. Since the earlier described
      ELISA has been validated for cell lysates and the antibody used for detection of
      HNE-protein adducts is non-commercial, the aim of this work was to adapt the
      ELISA to a commercial antibody and to apply it in the analysis of human plasma
      samples. AFTER MODIFICATION AND VALIDATION OF THE PROTOCOL FOR BOTH ANTIBODIES,
      SAMPLES OF TWO GROUPS WERE ANALYZED: apparently healthy obese (n=62) and non
      obese controls (n=15). Although the detected absolute values of HNE-protein
      adducts were different, depending on the antibody used, both ELISA methods showed
      significantly higher values of HNE-protein adducts in the obese group. 

PMID- 24024153
TI  - CFTR activity and mitochondrial function.
AB  - Cystic Fibrosis (CF) is a frequent and lethal autosomal recessive disease, caused
      by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance
      Regulator (CFTR). Before the discovery of the CFTR gene, several hypotheses
      attempted to explain the etiology of this disease, including the possible role of
      a chloride channel, diverse alterations in mitochondrial functions, the
      overexpression of the lysosomal enzyme alpha-glucosidase and a deficiency in the
      cytosolic enzyme glucose 6-phosphate dehydrogenase. Because of the diverse
      mitochondrial changes found, some authors proposed that the affected gene should
      codify for a mitochondrial protein. Later, the CFTR cloning and the demonstration
      of its chloride channel activity turned the mitochondrial, lysosomal and
      cytosolic hypotheses obsolete. However, in recent years, using new approaches,
      several investigators reported similar or new alterations of mitochondrial
      functions in Cystic Fibrosis, thus rediscovering a possible role of mitochondria
      in this disease. Here, we review these CFTR-driven mitochondrial defects,
      including differential gene expression, alterations in oxidative phosphorylation,
      calcium homeostasis, oxidative stress, apoptosis and innate immune response,
      which might explain some characteristics of the complex CF phenotype and reveals
      potential new targets for therapy. 

PMID- 24024157
TI  - Heme oxygenase-1 regulates postnatal lung repair after hyperoxia: role of beta
      catenin/hnRNPK signaling.
AB  - In the newborn, alveolarization continues postnatally and can be disrupted by
      hyperoxia, leading to long-lasting consequences on lung function. We wanted to
      better understand the role of heme oxygenase (HO)-1, the inducible form of the
      rate-limiting enzyme in heme degradation, in neonatal hyperoxic lung injury and
      repair. Although it was not observed after 3 days of hyperoxia alone, when
      exposed to hyperoxia and allowed to recover in air (O2/air recovered), neonatal
      HO-1 knockout (KO) mice had enlarged alveolar spaces and increased lung apoptosis
      as well as decreased lung protein translation and dysregulated gene expression in
      the recovery phase of the injury. Associated with these changes, KO had sustained
      low levels of active beta-catenin and lesser lung nuclear heterogeneous nuclear
      ribonucleoprotein K (hnRNPK) protein levels, whereas lung nuclear hnRNPK was
      increased in transgenic mice over-expressing nuclear HO-1. Disruption of HO-1 may
      enhance hnRNPK-mediated inhibition of protein translation and subsequently impair
      the beta-catenin/hnRNPK regulated gene expression required for coordinated lung
      repair and regeneration. 

PMID- 24024158
TI  - Teaching the basics of redox biology to medical and graduate students: Oxidants,
      antioxidants and disease mechanisms.
AB  - This article provides a succinct but limited overview of the protective and
      deleterious effects of reactive oxygen and nitrogen species in a clinical
      context. Reactive oxygen species include superoxide, hydrogen peroxide, single
      oxygen and lipid peroxides. Reactive nitrogen species include species derived
      from nitric oxide. This review gives a brief overview of the reaction chemistry
      of these species, the role of various enzymes involved in the generation and
      detoxification of these species in disease mechanisms and drug toxicity and the
      protective role of dietary antioxidants. I hope that the graphical review will be
      helpful for teaching both the first year medical and graduate students in the
      U.S. and abroad the fundamentals of reactive oxygen and nitrogen species in redox
      biology and clinical medicine. 

PMID- 24024159
TI  - Upregulation of the mitochondrial Lon Protease allows adaptation to acute
      oxidative stress but dysregulation is associated with chronic stress, disease,
      and aging.
AB  - The elimination of oxidatively modified proteins is a crucial process in
      maintaining cellular homeostasis, especially during stress. Mitochondria are
      protein-dense, high traffic compartments, whose polypeptides are constantly
      exposed to superoxide, hydrogen peroxide, and other reactive species, generated
      by 'electron leakage' from the respiratory chain. The level of oxidative stress
      to mitochondrial proteins is not constant, but instead varies greatly with
      numerous metabolic and environmental factors. Oxidized mitochondrial proteins
      must be removed rapidly (by proteolytic degradation) or they will aggregate,
      cross-link, and cause toxicity. The Lon Protease is a key enzyme in the
      degradation of oxidized proteins within the mitochondrial matrix. Under
      conditions of acute stress Lon is highly inducible, possibly with the oxidant
      acting as the signal inducer, thereby providing increased protection. It seems
      that under chronic stress conditions, however, Lon levels actually decline. Lon
      levels also decline with age and with senescence, and senescent cells even lose
      the ability to induce Lon during acute stress. We propose that the regulation of
      Lon is biphasic, in that it is up-regulated during transient stress and down
      regulated during chronic stress and aging, and we suggest that the loss of Lon
      responsiveness may be a significant factor in aging, and in age-related diseases.

PMID- 24024160
TI  - Acrolein-induced activation of mitogen-activated protein kinase signaling is
      mediated by alkylation of thioredoxin reductase and thioredoxin 1.
AB  - Cigarette smoking remains a major health concern worldwide, and many of the
      adverse effects of cigarette smoke (CS) can be attributed to its abundant
      electrophilic aldehydes, such as acrolein (2-propenal). Previous studies indicate
      that acrolein readily reacts with thioredoxin reductase 1 (TrxR1), a critical
      enzyme involved in regulation of thioredoxin (Trx)-mediated redox signaling, by
      alkylation at its selenocysteine (Sec) residue. Because alkylation of Sec within
      TrxR1 has significant implications for its enzymatic function, we explored the
      potential importance of TrxR1 alkylation in acrolein-induced activation or injury
      of bronchial epithelial cells. Exposure of human bronchial epithelial HBE1 cells
      to acrolein (1-30 MUM) resulted in dose-dependent loss of TrxR thioredoxin
      reductase activity, which coincided with its alkylation, as determined by biotin
      hydrazide labeling, and was independent of initial GSH status. To test the
      involvement of TrxR1 in acrolein responses in HBE1 cells, we suppressed TrxR1
      using siRNA silencing or augmented TrxR1 by cell supplementation with sodium
      selenite. Acrolein exposure of HBE1 cells induced dose-dependent activation of
      the MAP kinases, extracellular regulated kinase (ERK), c-Jun N-terminal kinase
      (JNK), and p38, and activation of JNK was markedly enhanced after selenite
      mediated induction of TrxR1, and was associated with increased alkylation of
      TrxR1. Conversely, siRNA silencing of TrxR1 significantly suppressed the ability
      of acrolein to activate JNK, and also appeared to attenuate acrolein-dependent
      activation of ERK and p38. Alteration of initial TrxR1 levels by siRNA or
      selenite supplementation also affected initial Trx1 redox status and acrolein
      mediated alkylation of Trx1, but did not significantly affect acrolein-mediated
      activation of HO-1 or cytotoxicity. Collectively, our findings indicate that
      alkylation of TrxR1 and/or Trx1 may contribute directly to acrolein-mediated
      activation of MAP kinases such as JNK, and may therefore be important in acrolein
      induced alterations in airway epithelial function, as a contributing mechanism in
      tobacco-related respiratory disease. 

PMID- 24024162
TI  - Thioredoxin interacting protein and its association with clinical outcome in
      gastro-oesophageal adenocarcinoma.
AB  - The overall prognosis for operable gastro-oesophageal adenocarcinoma remains poor
      and therefore neoadjuvant chemotherapy has become the standard of care, in
      addition to radical surgery. Certain anticancer agents (e.g. anthracyclines and
      cisplatin) generate damaging reactive oxygen species as by-products of their
      mechanism of action. Drug effectiveness can therefore depend upon the presence of
      cellular redox buffering systems that are often deregulated in cancer. The
      expression of the redox protein, thioredoxin interacting protein, was assessed in
      gastro-oesophageal adenocarcinomas. Thioredoxin interacting protein expression
      was assessed using conventional immunohistochemistry on a tissue microarray of
      140 adenocarcinoma patients treated by primary surgery alone and 88 operable
      cases treated with neoadjuvant chemotherapy. In the primary surgery cases, high
      thioredoxin interacting protein expression associated with a lack of lymph node
      involvement (p=0.005), no perineural invasion (p=0.030) and well/moderate tumour
      differentiation (p=0.033). In the neoadjuvant tumours, high thioredoxin
      interacting protein expression was an independent marker for improved disease
      specific survival (p=0.002) especially in cases with anthracycline-based regimes
      (p=0.008). This study highlights the potential of thioredoxin interacting protein
      as a biomarker for response in neoadjuvant treated gastro-oesophageal
      adenocarcinoma and may represent a useful therapeutic target due to its
      association with tumour progression. 

PMID- 24024161
TI  - The redox interplay between nitrite and nitric oxide: From the gut to the brain.
AB  - The reversible redox conversion of nitrite and nitric oxide ((*)NO) in a
      physiological setting is now widely accepted. Nitrite has long been identified as
      a stable intermediate of (*)NO oxidation but several lines of evidence support
      the reduction of nitrite to nitric oxide in vivo. In the gut, this notion implies
      that nitrate from dietary sources fuels the longstanding production of nitrite in
      the oral cavity followed by univalent reduction to (*)NO in the stomach. Once
      formed, (*)NO boosts a network of reactions, including the production of higher
      nitrogen oxides that may have a physiological impact via the post-translational
      modification of proteins and lipids. Dietary compounds, such as polyphenols, and
      different prandial states (secreting specific gastric mediators) modulate the
      outcome of these reactions. The gut has unusual characteristics that modulate
      nitrite and (*)NO redox interplay: (1) wide range of pH (neutral vs acidic) and
      oxygen tension (c.a. 70 Torr in the stomach and nearly anoxic in the colon), (2)
      variable lumen content and (3) highly developed enteric nervous system (sensitive
      to (*)NO and dietary compounds, such as glutamate). The redox interplay of
      nitrite and (*)NO might also participate in the regulation of brain homeostasis
      upon neuronal glutamatergic stimulation in a process facilitated by ascorbate and
      a localized and transient decrease of oxygen tension. In a way reminiscent of
      that occurring in the stomach, a nitrite/(*)NO/ascorbate redox interplay in the
      brain at glutamatergic synapses, contributing to local (*)NO increase, may impact
      on (*)NO-mediated process. We here discuss the implications of the redox
      conversion of nitrite to (*)NO in the gut, how nitrite-derived (*)NO may signal
      from the digestive to the central nervous system, influencing brain function, as
      well as a putative ascorbate-driven nitrite/NO pathway occurring in the brain. 

PMID- 24024163
TI  - Extracellular but not cytosolic superoxide dismutase protects against oxidant
      mediated endothelial dysfunction.
AB  - Superoxide (O2 (*-)) contributes to the development of cardiovascular disease.
      Generation of O2 (*-) occurs in both the intracellular and extracellular
      compartments. We hypothesized that the gene transfer of cytosolic superoxide
      dismutase (SOD1) or extracellular SOD (SOD3) to blood vessels would
      differentially protect against O2 (*-)-mediated endothelial-dependent
      dysfunction. Aortic ring segments from New Zealand rabbits were incubated with
      adenovirus (Ad) containing the gene for Escherichia coli beta-galactosidase,
      SOD1, or SOD3. Activity assays confirmed functional overexpression of both SOD3
      and SOD1 isoforms in aorta 24 h following gene transfer. Histochemical staining
      for beta-galactosidase showed gene transfer occurred in the endothelium and
      adventitia. Next, vessels were prepared for measurement of isometric tension in
      Kreb's buffer containing xanthine. After precontraction with phenylephrine,
      xanthine oxidase impaired relaxation to the endothelium-dependent dilator
      acetylcholine (ACh, max relaxation 33+/-4% with XO vs. 64+/-3% without XO,
      p<0.05), whereas relaxation to the endothelium-independent dilator sodium
      nitroprusside was unaffected. In the presence of XO, maximal relaxation to ACh
      was improved in vessels incubated with AdSOD3 (55+/-2%, p<0.05 vs. control) but
      not AdSOD1 (34+/-4%). We conclude that adenoviral-mediated gene transfer of SOD3,
      but not SOD1, protects the aorta from xanthine/XO-mediated endothelial
      dysfunction. These data provide important insight into the location and enzymatic
      source of O2 (*-) production in vascular disease. 

PMID- 24024164
TI  - Prolonging in utero-like oxygenation after birth diminishes oxidative stress in
      the lung and brain of mice pups.
AB  - BACKGROUND: Fetal-to-neonatal transition is associated with oxidative stress. In
      preterm infants, immaturity of the antioxidant system favours supplemental oxygen
      derived morbidity and mortality. OBJECTIVES: To assess if prolonging in utero
      like oxygenation during the fetal-to-neonatal transition limits oxidative stress
      in the lung and brain, improving postnatal adaptation of mice pups. MATERIAL AND
      METHODS: Inspiratory oxygen fraction (FiO2) in pregnant mice was reduced from 21%
      (room air) to 14% (hypoxia) 8-12 h prior to delivery and reset to 21% 6-8 h after
      birth. The control group was kept at 21% during the procedure. Reduced (GSH) and
      oxidized (GSSG) glutathione and its precursors [gamma-glutamyl cysteine (gamma
      GC) and L-cysteine (CySH)] content and expression of several redox-sensitive
      genes were evaluated in newborn lung and brain tissue 1 (P1) and 7 (P7) days
      after birth. RESULTS: As compared with control animals, the GSH/GSSG ratio was
      increased in the hypoxic group at P1 and P7 in the lung, and at P7 in the brain.
      In the hypoxic group a significant increase in the mRNA levels of NAD(P)H:quinone
      oxidoreductase 1 (noq1), Sulfiredoxin 1 (srnx1) and Glutathione Peroxidase 1
      (gpx) was found in lung tissue at P1, as well as a significant increase in gpx in
      brain tissue at P7. CONCLUSIONS: Delaying the increase in tissue oxygenation to
      occur after birth reduces short-and-long-term oxidative stress in the lung.
      Similar yet more subtle effects were found in the brain. Apparently, the fetal-to
      neonatal transition under hypoxic conditions appears to have protective
      qualities.

PMID- 24024165
TI  - Sites of reactive oxygen species generation by mitochondria oxidizing different
      substrates.
AB  - Mitochondrial radical production is important in redox signaling, aging and
      disease, but the relative contributions of different production sites are poorly
      understood. We analyzed the rates of superoxide/H2O2 production from different
      defined sites in rat skeletal muscle mitochondria oxidizing a variety of
      conventional substrates in the absence of added inhibitors: succinate; glycerol 3
      phosphate; palmitoylcarnitine plus carnitine; or glutamate plus malate. In all
      cases, the sum of the estimated rates accounted fully for the measured overall
      rates. There were two striking results. First, the overall rates differed by an
      order of magnitude between substrates. Second, the relative contribution of each
      site was very different with different substrates. During succinate oxidation,
      most of the superoxide production was from the site of quinone reduction in
      complex I (site IQ), with small contributions from the flavin site in complex I
      (site IF) and the quinol oxidation site in complex III (site IIIQo). However,
      with glutamate plus malate as substrate, site IQ made little or no contribution,
      and production was shared between site IF, site IIIQo and 2-oxoglutarate
      dehydrogenase. With palmitoylcarnitine as substrate, the flavin site in complex
      II (site IIF) was a major contributor (together with sites IF and IIIQo), and
      with glycerol 3-phosphate as substrate, five different sites all contributed,
      including glycerol 3-phosphate dehydrogenase. Thus, the relative and absolute
      contributions of specific sites to the production of reactive oxygen species in
      isolated mitochondria depend very strongly on the substrates being oxidized, and
      the same is likely true in cells and in vivo. 

PMID- 24024166
TI  - A tale of two gases: NO and H2S, foes or friends for life?
AB  - Nitric oxide (NO) and hydrogen sulfide (H2S) have emerged as dominant redox
      regulators of numerous aspects of cellular and physiological functions within
      several organ systems included cardiovascular, immune and neurological tissues.
      Recent studies have begun to reveal that these two gaseous molecules may have
      redundant or overlapping pathophysiological functions often involving similar
      molecular targets. However, it remains less clear when and how NO and H2S may
      interact under biological and disease processes. In this graphical review, we
      discuss the current understanding of NO and H2S interactions and how they may
      functionally influence each other and what this may mean for biology and
      mechanisms of disease. 

PMID- 24024168
TI  - Novel device for continuous spatial control and temporal delivery of nitric oxide
      for in vitro cell culture.
AB  - Nitric oxide (NO) is an ubiquitous signaling molecule of intense interest in many
      physiological processes. Nitric oxide is a highly reactive free radical gas that
      is difficult to deliver with precise control over the level and timing that cells
      actually experience. We describe and characterize a device that allows tunable
      fluxes and patterns of NO to be generated across the surface upon which cells are
      cultured. The system is based on a quartz microscope slide that allows for
      controlled light levels to be applied to a previously described photosensitive NO
      releasing polydimethylsiloxane (PDMS). Cells are cultured in separate wells that
      are either NO-releasing or a chemically similar PDMS that does not release NO.
      Both wells are then top coated with DowCorning RTV-3140 PDMS and a
      polydopamine/gelatin layer to allow cells to grow in the culture wells. When the
      waveguide is illuminated, the surface of the quartz slide propagates light such
      that the photosensitive polymer is evenly irradiated and generates NO across the
      surface of the cell culture well and no light penetrates into the volume of the
      wells where cells are growing. Mouse smooth muscle cells (MOVAS) were grown in
      the system in a proof of principle experiment, whereby 60% of the cells were
      present in the NO-releasing well compared to control wells after 17 h. The
      compelling advantage of illuminating the NO-releasing polymers with the waveguide
      system is that light can be used to tunably control NO release while avoiding
      exposing cells to optical radiation. This device provides means to quantitatively
      control the surface flux, timing and duration of NO cells experience and allows
      for systematic study of cellular response to NO generated at the cell/surface
      interface in a wide variety of studies. 

PMID- 24024169
TI  - Sex hormones modulate circulating antioxidant enzymes: impact of estrogen
      therapy.
AB  - OBJECTIVE: Ovarian senescence affects many tissues and produces a variety of
      symptoms and signs. We hypothesized that estrogens may also influence circulating
      redox balance by regulating activity of the cellular antioxidative enzyme system.
      We aimed to explore the impact of surgical estrogen deprivation and replacement
      (ERT) on the glutathione balance and antioxidant enzymes expression in fertile
      women. STUDY DESIGN: Nineteen healthy premenopausal women who underwent total
      hysterectomy with bilateral salpingo-oophorectomy were evaluated at baseline, 30
      days after surgery without ERT and 30 days after ERT. Redox balance was
      determined by measuring blood reduced (GSH) and oxidized (GSSG) glutathione, as
      well as the GSSG/GSH ratio. Antioxidant status was evaluated by measuring serum
      estrogen (E2) levels and mRNA expression of superoxide dismutase (SOD), catalase
      (CAT), glutathione peroxidase (GSH-Px) and glutathione S-transferase (GST) in
      peripheral blood mononuclear cells. RESULTS: Serum E2 significantly lowered after
      surgery, and increased in 12 out of 19 patients after 30 days of ERT
      (Responders). In such patients, an increase in oxidative stress was observed
      after surgery that resolved after ERT. Oxidative stress was sustained by
      reduction in the mRNA expression of both SOD and GSH-Px, that recovered after 30
      days of therapy in responders. CAT and GST mRNA expression were not modified by
      surgery and replacement therapy. CONCLUSIONS: Menopause is associated with
      significant change in antioxidant gene expression that in turn affects
      circulating redox state. Estrogens replacement therapy is able to prevent and
      counteract such modifications by acting as regulators of key antioxidant gene
      expression. These findings suggest that antioxidant genes are, almost in part,
      under the control of sex hormones, and that pathophysiology of the difference in
      gender disease may depend on the redox biology.

PMID- 24024167
TI  - Effects of 4-hydroxynonenal on vascular endothelial and smooth muscle cell redox
      signaling and function in health and disease.
AB  - 4-hydroxynonenal (HNE) is a lipid hydroperoxide end product formed from the
      oxidation of n-6 polyunsaturated fatty acids. The relative abundance of HNE
      within the vasculature is dependent not only on the rate of lipid peroxidation
      and HNE synthesis but also on the removal of HNE adducts by phase II metabolic
      pathways such as glutathione-S-transferases. Depending on its relative
      concentration, HNE can induce a range of hormetic effects in vascular endothelial
      and smooth muscle cells, including kinase activation, proliferation, induction of
      phase II enzymes and in high doses inactivation of enzymatic processes and
      apoptosis. HNE also plays an important role in the pathogenesis of vascular
      diseases such as atherosclerosis, diabetes, neurodegenerative disorders and in
      utero diseases such as pre-eclampsia. This review examines the known production,
      metabolism and consequences of HNE synthesis within vascular endothelial and
      smooth muscle cells, highlighting alterations in mitochondrial and endoplasmic
      reticulum function and their association with various vascular pathologies. 

PMID- 24024170
TI  - A quantitative study of the cell-type specific modulation of c-Rel by hydrogen
      peroxide and TNF-alpha.
AB  - Hydrogen peroxide (H2O2) at moderate steady-state concentrations synergizes with
      TNF-alpha, leading to increased nuclear levels of NF-kappaB p65 subunit and to a
      cell-type specific up-regulation of a limited number of NF-kappaB-dependent
      genes. Here, we address how H2O2 achieves this molecular specificity. HeLa and
      MCF-7 cells were exposed to steady-state H2O2 and/or TNF-alpha and levels of c
      Rel, p65, IkappaB-alpha, IkappaB-beta and IkappaB-epsilon were determined. For an
      extracellular concentration of 25 uM H2O2, the intracellular H2O2 concentration
      is 3.7 uM and 12.5 uM for respectively HeLa and MCF-7 cells. The higher cytosolic
      H2O2 concentration present in MCF-7 cells may be a contributing factor for the
      higher activation of NF-kappaB caused by H2O2 in this cell line, when compared to
      HeLa cells. In both cells lines, H2O2 precludes the recovery of TNF-alpha
      dependent IkappaB-alpha degradation, which may explain the observed synergism
      between H2O2 and TNF-alpha concerning p65 nuclear translocation. In MCF-7 cells,
      H2O2, in the presence of TNF-alpha, tripled the induction of c-Rel triggered
      either by TNF-alpha or H2O2. Conversely, in HeLa cells, H2O2 had a small
      antagonistic effect on TNF-alpha-induced c-Rel nuclear levels, concomitantly with
      a 50 % induction of IkappaB-epsilon, the preferential inhibitor protein of c-Rel
      dimers. The 6-fold higher c-Rel/IkappaB-epsilon ratio found in MCF-7 cells when
      compared with HeLa cells, may be a contributing factor for the cell-type
      dependent modulation of c-Rel by H2O2. Our results suggest that H2O2 might have
      an important cell-type specific role in the regulation of c-Rel-dependent
      processes, e.g. cancer or wound healing. 

PMID- 24024171
TI  - Xanthine oxidoreductase-catalyzed reactive species generation: A process in
      critical need of reevaluation.
AB  - Nearly 30 years have passed since the discovery of xanthine oxidoreductase (XOR)
      as a critical source of reactive species in ischemia/reperfusion injury. Since
      then, numerous inflammatory disease processes have been associated with elevated
      XOR activity and allied reactive species formation solidifying the ideology that
      enhancement of XOR activity equates to negative clinical outcomes. However,
      recent evidence may shatter this paradigm by describing a nitrate/nitrite
      reductase capacity for XOR whereby XOR may be considered a crucial source of
      beneficial (*)NO under ischemic/hypoxic/acidic conditions; settings similar to
      those that limit the functional capacity of nitric oxide synthase. Herein, we
      review XOR-catalyzed reactive species generation and identify key
      microenvironmental factors whose interplay impacts the identity of the reactive
      species (oxidants vs. (*)NO) produced. In doing so, we redefine existing dogma
      and shed new light on an enzyme that has weathered the evolutionary process not
      as gadfly but a crucial component in the maintenance of homeostasis. 

PMID- 24024172
TI  - Glucose availability is a decisive factor for Nrf2-mediated gene expression.
AB  - Activation of the transcription factor Nrf2 (nuclear factor-erythroid 2-related
      factor 2) is one of the major cellular defense lines against oxidative and
      xenobiotic stress, but also influences genes involved in lipid and glucose
      metabolism. It is unresolved whether the cytoprotective and metabolic responses
      mediated by Nrf2 are connected or separable events in non-malignant cells. In
      this study we show that activation of Nrf2, either by the small molecule
      sulforaphane or knockout of the Nrf2 inhibitor Keap1, leads to increased cellular
      glucose uptake and increased glucose addiction in fibroblasts. Upon Nrf2
      activation glucose is preferentially metabolized through the pentose phosphate
      pathway with increased production of NADPH. Interference with the supply of
      glucose or the pentose phosphate pathway and NADPH generation not only hampers
      Nrf2-mediated detoxification of reactive oxygen species on the enzyme level but
      also Nrf2-initiated expression of antioxidant defense proteins, such as
      glutathione reductase and heme-oxygenase1. We conclude that the Nrf2-dependent
      protection against oxidative stress relies on an intact pentose phosphate pathway
      and that there is crosstalk between metabolism and detoxification already at the
      level of gene expression in mammalian cells. 

PMID- 24024173
TI  - Cullin 3 as a novel target in diverse pathologies.
AB  - Recent evidence suggests that the malfunctioning disposal system of cell protein
      called ubiquitin-proteasome system (UPS) plays an important role in the
      development of disorders, including cancer and neurodegenerative diseases.
      Accumulating evidence suggests that the abnormal regulation of the E3 ubiquitin
      ligases, essential components of the UPS, contributes to uncontrolled
      proliferation, genomic instability and cancer, since these ligases and their
      substrates are involved in the regulation of cell cycle progression, gene
      transcription, signal transduction, DNA replication and others. Through selective
      degradation of specific substrates, E3 ligases regulate different biological
      processes. Cullins are a family of proteins that confer substrate specificity to
      multimeric complex of E3 ligases acting as scaffold proteins. So far, seven
      members of the cullin family of proteins have been identified. Interestingly, the
      data generated by several groups indicate that cullin 3 (Cul3) has begun to
      emerge as a protein involved in the etiopathology of multiple diseases. In this
      paper we examine the latest advances in basic research on the biology of Cul3 and
      how it could help to direct drug discovery efforts on this target. 

PMID- 24024174
TI  - Protein disulfide isomerase may facilitate the efflux of nitrite derived S
      nitrosothiols from red blood cells.
AB  - Protein disulfide isomerase (PDI) is an abundant protein primarily found in the
      endoplasmic reticulum and also secreted into the blood by a variety of vascular
      cells. The evidence obtained here, suggests that PDI could directly participate
      in the efflux of NO(+) from red blood cells (RBC). PDI was detected both in RBC
      membranes and in the cytosol. PDI was S-nitrosylated when RBCs were exposed to
      nitrite under ~50% oxygen saturation but not under ~100% oxygen saturation.
      Furthermore, it was observed that hemoglobin (Hb) could promote PDI S
      nitrosylation in the presence of ~600 nM nitrite. In addition, three lines of
      evidence were obtained for PDI-Hb interactions: (1) Hb co-immunoprecipitated with
      PDI; (2) Hb quenched the intrinsic PDI fluorescence in a saturable manner; and
      (3) Hb-Fe(II)-NO absorption spectrum decreased in a [PDI]-dependent manner.
      Finally, PDI was detected on the surface RBC under ~100% oxygen saturation and
      released as soluble under ~50% oxygen saturation. The soluble PDI detected under
      ~50% oxygen saturation was S-nitrosylated. Based on these data it is proposed
      that PDI is taken up by RBC and forms a complex with Hb. Hb-Fe(II)-NO that is
      formed from nitrite reduction under ~50% O2, then transfers NO(+) to either Hb
      Cys beta93 or directly to PDI resulting in S-nitroso-PDI which transverses the
      RBC membrane and attaches to the RBC surface. When RBCs enter tissues the S
      nitroso-PDI is released from the RBC-surface into the blood where its NO(+) is
      transferred into the endothelium thereby inducing vasodilation, suggesting local
      oxygen-dependent dynamic interplays between nitrite, NO and S-nitrosylation. 

PMID- 24024175
TI  - Quercetin prevents left ventricular hypertrophy in the Apo E knockout mouse.
AB  - Hypercholesterolemia is a risk factor for the development of hypertrophic
      cardiomyopathy. Nevertheless, there are few studies aimed at determining the
      effects of dietary compounds on early or mild cardiac hypertrophy associated with
      dyslipidemia. Here we describe left ventricular (LV) hypertrophy in 12 week-old
      Apo E(-/-) hypercholesterolemic mice. The LV end diastolic posterior wall
      thickness and overall LV mass were significantly increased in Apo E(-/-) mice
      compared with wild type (WT) controls. Fractional shortening, LV end diastolic
      diameter, and hemodynamic parameters were unchanged from WT mice. Oral low dose
      quercetin (QCN; 0.1 umol QCN/kg body weight for 6 weeks) significantly reduced
      total cholesterol and very low density lipoprotein in the plasma of Apo E(-/-)
      mice. QCN treatment also significantly decreased LV posterior wall thickness and
      LV mass in Apo E(-/-) mice. Myocardial geometry and function were unaffected in
      WT mice by QCN treatment. These data suggest that dietary polyphenolic compounds
      such as QCN may be effective modulators of plasma cholesterol and could prevent
      maladaptive myocardial remodeling. 

PMID- 24024176
TI  - Characterization of plasma thiol redox potential in a common marmoset model of
      aging.
AB  - Due to its short lifespan, ease of use and age-related pathologies that mirror
      those observed in humans, the common marmoset (Callithrix jacchus) is poised to
      become a standard nonhuman primate model of aging. Blood and extracellular fluid
      possess two major thiol-dependent redox nodes involving cysteine (Cys), cystine
      (CySS), glutathione (GSH) and glutathione disulfide (GSSG). Alteration in these
      plasma redox nodes significantly affects cellular physiology, and oxidation of
      the plasma Cys/CySS redox potential (E hCySS) is associated with aging and
      disease risk in humans. The purpose of this study was to determine age-related
      changes in plasma redox metabolites and corresponding redox potentials (E h) to
      further validate the marmoset as a nonhuman primate model of aging. We measured
      plasma thiol redox states in marmosets and used existing human data with
      multivariate adaptive regression splines (MARS) to model the relationships
      between age and redox metabolites. A classification accuracy of 70.2% and an AUC
      of 0.703 were achieved using the MARS model built from the marmoset redox data to
      classify the human samples as young or old. These results show that common
      marmosets provide a useful model for thiol redox biology of aging. 

PMID- 24024177
TI  - Potential therapeutic effects of the simultaneous targeting of the Nrf2 and NF
      kappaB pathways in diabetic neuropathy.
AB  - The Nuclear factor-2 erythroid related factor-2 (Nrf2) is a redox regulated
      transcription factor involved in the regulation of antioxidant defence systems.
      It drives the production of endogenous antioxidant defences and detoxifying
      enzymes. Nuclear factor-kappa light chain enhancer of B cells (NF-kappaB) is a
      transcription factor, involved in proinflammatory cytokine production, in
      addition to its immunological function. Both Nrf2 and NF-kappaB regulation are co
      ordinated in order to maintain redox homeostasis in healthy cells. However,
      during pathological conditions this regulation is perturbed offering an
      opportunity for therapeutic intervention. Diabetic neuropathy is a condition, in
      which change in expression pattern of Nrf2 and NF-kappaB has been reported. This
      review aims to focus on the role of the Nrf2 and NF-kappaB in diabetic neuropathy
      and summarizes the therapeutic outcomes of various pharmacological modulators
      targeted at the Nrf2-NF-kappaB axis in diabetic neuropathy. 

PMID- 24024178
TI  - SDOCT thickness measurements of various retinal layers in patients with autosomal
      dominant optic atrophy due to OPA1 mutations.
AB  - PURPOSE: To specify thickness values of various retinal layers on macular
      spectral domain Optical Coherence Tomography (SDOCT) scans in patients with
      autosomal dominant optic atrophy (ADOA) compared to healthy controls. METHODS:
      SDOCT volume scans of 7 patients with ADOA (OPA-1 mutation) and 14 healthy
      controls were quantitatively analyzed using manual grading software. Mean
      thickness values for the ETDRS grid subfields 5-8 were calculated for the spaces
      neurosensory retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL),
      a combined space of inner plexiform layer/outer plexiform layer/inner nuclear
      layer (IPL+INL+OPL), and a combined space of outer nuclear layer/photoreceptor
      layers (ONL+PL). RESULTS: ADOA patients showed statistically significant lower
      retinal thickness values than controls (P < 0.01). RNFL (P < 0.001) and GCL
      thicknesses (P < 0.001) were significantly lower in ADOA patients. There was no
      difference in IPL+INL+OPL and in ONL+PL thickness. CONCLUSION: Manual subanalysis
      of macular SDOCT volume scans allowed detailed subanalysis of various retinal
      layers. Not only RNFL but also GCL thicknesses are reduced in the macular area of
      ADOA patients whereas subjacent layers are not involved. Together with clinical
      findings, macular SDOCT helps to identify patients with suspicion for hereditary
      optic neuropathy before genetic analysis confirms the diagnosis.

PMID- 24024179
TI  - Degenerative spondylolisthesis is associated with low spinal bone density: a
      comparative study between spinal stenosis and degenerative spondylolisthesis.
AB  - Spinal stenosis and degenerative spondylolisthesis share many symptoms and the
      same treatment, but their causes remain unclear. Bone mineral density has been
      suggested to play a role. The aim of this study was to investigate differences in
      spinal bone density between spinal stenosis and degenerative spondylolisthesis
      patients. 81 patients older than 60 years, who underwent DXA-scanning of their
      lumbar spine one year after a lumbar spinal fusion procedure, were included.
      Radiographs were assessed for disc height, vertebral wedging, and osteophytosis.
      Pain was assessed using the Low Back Pain Rating Scale pain index. T-score of the
      lumbar spine was significantly lower among degenerative spondylolisthesis
      patients compared with spinal stenosis patients (-1.52 versus -0.52, P = 0.04).
      Thirty-nine percent of degenerative spondylolisthesis patients were classified as
      osteoporotic and further 30% osteopenic compared to only 9% of spinal stenosis
      patients being osteoporotic and 30% osteopenic (P = 0.01). Pain levels tended to
      increase with poorer bone status (P = 0.06). Patients treated surgically for
      symptomatic degenerative spondylolisthesis have much lower bone mass than
      patients of similar age treated surgically for spinal stenosis. Low BMD might
      play a role in the development of the degenerative spondylolisthesis, further
      studies are needed to clarify this. 

PMID- 24024180
TI  - Effect of mesenchymal stem cells and a novel curcumin derivative on Notch1
      signaling in hepatoma cell line.
AB  - This study was conducted to evaluate the effect of mesenchymal stem cells (MSCs)
      and a novel curcumin derivative (NCD) on HepG2 cells (hepatoma cell line) and to
      investigate their effect on Notch1 signaling pathway target genes. HepG2 cells
      were divided into HepG2 control group, HepG2 cells treated with MSC conditioned
      medium (MSCs CM), HepG2 cells treated with a NCD, HepG2 cells treated with MSCs
      CM and NCD, and HepG2 cells treated with MSCs CM (CM of MSCs pretreated with a
      NCD). Expression of Notch1, Hes1, VEGF, and cyclin D1 was assessed by real-time,
      reverse transcription-polymerase chain reaction (RT-PCR) in HepG2 cells. In
      addition, HepG2 proliferation assay was performed in all groups. Notch1 and its
      target genes (Hes1 and cyclin D1) were downregulated in all treated groups with
      more suppressive effect in the groups treated with both MSCs and NCD. Also,
      treated HepG2 cells showed significant decrease in cell proliferation rate. These
      data suggest that modulation of Notch1 signaling pathway by MSCs and/or NCD can
      be considered as a therapeutic target in HCC. 

PMID- 24024181
TI  - Clinicopathological impact of ABCC1/MRP1 and ABCC4/MRP4 in epithelial ovarian
      carcinoma.
AB  - Ovarian cancer is the main cause of death from gynaecological malignancies. In
      spite of the efficacy of platinum-paclitaxel treatment in patients with primary
      epithelial ovarian carcinoma, platinum-based chemotherapy is not curative and
      resistance remains one of the most important causes of treatment failure.
      Although ABC transporters have been implicated in cellular resistance to multiple
      drugs, the clinical relevance of these efflux pumps is still poorly understood.
      Thus, we examined the prognostic role of transporters of the MRP family (i.e.,
      ABCC1/MRP1, ABCC4/MRP4) to gain insights into their clinical impacts. A case
      material of 127 patients with ovarian carcinoma at different stages and
      histotypes was used. The expression of MRP1 and MRP4 was examined by
      immunohistochemistry using tissue microarrays in tumor specimens collected at the
      time of initial surgery expression. We found an association between MRP1
      expression and grading, and we observed that MRP4 displayed an unfavourable
      impact on disease relapse in multivariate analysis (HR = 2.05, 95% CI: 1.01-4.11;
      P = 0.045). These results suggest that in epithelial ovarian cancer, MRP1 may be
      a marker for aggressiveness because its expression was associated with tumor
      grade and support that MRP4 may play an unfavourable role in disease outcome. 

PMID- 24024182
TI  - Simulated microgravity combined with polyglycolic acid scaffold culture
      conditions improves the function of pancreatic islets.
AB  - The in vitro culture of pancreatic islets reduces their immunogenicity and
      prolongs their availability for transplantation. Both simulated microgravity
      (sMG) and a polyglycolic acid scaffold (PGA) are believed to confer advantages to
      cell culture. Here, we evaluated the effects of sMG combined with a PGA on the
      viability, insulin-producing activity and morphological alterations of pancreatic
      islets. Under PGA-sMG conditions, the purity of the islets was >=85%, and the
      islets had a higher survival rate and an increased ability to secrete insulin
      compared with islets cultured alone in the static, sMG, or PGA conditions. In
      addition, morphological analysis under scanning electron microscopy (SEM)
      revealed that the PGA-sMG treatment preserved the integral structure of the
      islets and facilitated islet adhesion to the scaffolds. These results suggest
      that PGA-sMG coculture has the potential to improve the viability and function of
      islets in vitro and provides a promising method for islet transplantation.

PMID- 24024183
TI  - Quality of life in Parkinson's disease caregivers: the contribution of
      personality traits.
AB  - Parkinson's disease imposes significant demands not only on patients but also on
      those people living and caring for them, who often have a reduction in their
      quality of life. The factors that may ameliorate these effects, such as an
      individual's personality, are not understood. Therefore, the aim of this study
      was to look at the relative contribution of caregiver personality on their
      quality of life, specifically attempting to identify those traits, which may be
      protective or harmful. Two hundred and seventy-four caregivers of patients with
      Parkinson's disease were included in this study. Caregivers were given
      questionnaires to complete, including the Big Five Inventory and the World Health
      Organisation Quality of Life BREF version. Univariate correlations demonstrated
      that depression and anxiety were the largest predictors of reduced quality of
      life amongst caregivers. However, after controlling for these potential
      confounds, conscientiousness was associated with enhanced psychological quality
      of life and openness positively predicted benefits in the environmental domain.
      Neuroticism was associated with reduced quality of life in the psychological
      domain. Thus, screening for neuroticism may help identify those caregivers who
      would benefit from intervention strategies, which could in the long term help
      reduce the need for nursing home placement of Parkinson's disease patients. 

PMID- 24024185
TI  - End-systolic elastance and ventricular-arterial coupling reserve predict cardiac
      events in patients with negative stress echocardiography.
AB  - BACKGROUND: A maximal negative stress echo identifies a low-risk subset for
      coronary events. However, the potentially prognostically relevant information on
      cardiovascular hemodynamics for heart-failure-related events is unsettled. Aim of
      this study was to assess the prognostic value of stress-induced variation in
      cardiovascular hemodynamics in patients with negative stress echocardiography.
      METHODS: We enrolled 891 patients (593 males mean age 63 +/- 12, ejection
      fraction 48 +/- 17%), with negative (exercise 172, dipyridamole 482, and
      dobutamine 237) stress echocardiography result. During stress we assessed left
      ventricular end-systolic elastance index (E(LV)I), ventricular arterial coupling
      (VAC) indexed by the ratio of the E(LV)I to arterial elastance index (E aI),
      systemic vascular resistance (SVR), and pressure-volume area (PVA). Changes from
      rest to peak stress (reserve) were tested as predictors of main outcome measures:
      combined death and heart failure hospitalization. RESULTS: During a median
      followup of 19 months (interquartile range 8-36), 50 deaths and 84
      hospitalization occurred. Receiver-operating-characteristic curves identified as
      best predictors E(LV)I reserve for exercise (AUC = 0.871) and dobutamine (AUC =
      0.848) and VAC reserve (AUC = 0.696) for dipyridamole. CONCLUSIONS: Patients with
      negative stress echocardiography may experience an adverse outcome, which can be
      identified by assessment of E(LV)I reserve and VAC reserve during stress echo.

PMID- 24024186
TI  - Diagnostic procedures and management of dry eye.
AB  - Dry eye disease or dysfunctional tear syndrome is among the most frequent
      diagnoses in ophthalmology. It is a multifactorial disease of the ocular surface
      and tear film which results in ocular discomfort, visual disturbances, and tear
      instability with potential damage to the cornea and conjunctiva. Risk factors for
      dry eye syndrome include age, sex (female gender), race, contact lens wear,
      environment with low humidity, systemic medications, and autoimmune disorders.
      The aim of this paper is to present the systematic classification, epidemiology,
      diagnostic procedures, and advances in the management of dry eye disease. The
      recent improvements in comprehending the underlying etiologic factors will
      inevitably improve future classifications and diagnostic abilities leading to
      more effective therapeutic options. Treatment of this highly prevalent condition
      can drastically improve the quality of life of individuals and prevent damage to
      the ocular surface. 

PMID- 24024184
TI  - Trypanosoma evansi and surra: a review and perspectives on origin, history,
      distribution, taxonomy, morphology, hosts, and pathogenic effects.
AB  - Trypanosoma evansi, the agent of "surra," is a salivarian trypanosome,
      originating from Africa. It is thought to derive from Trypanosoma brucei by
      deletion of the maxicircle kinetoplastic DNA (genetic material required for
      cyclical development in tsetse flies). It is mostly mechanically transmitted by
      tabanids and stomoxes, initially to camels, in sub-Saharan area. The disease
      spread from North Africa towards the Middle East, Turkey, India, up to 53 degrees
      North in Russia, across all South-East Asia, down to Indonesia and the
      Philippines, and it was also introduced by the conquistadores into Latin America.
      It can affect a very large range of domestic and wild hosts including camelids,
      equines, cattle, buffaloes, sheep, goats, pigs, dogs and other carnivores, deer,
      gazelles, and elephants. It found a new large range of wild and domestic hosts in
      Latin America, including reservoirs (capybaras) and biological vectors (vampire
      bats). Surra is a major disease in camels, equines, and dogs, in which it can
      often be fatal in the absence of treatment, and exhibits nonspecific clinical
      signs (anaemia, loss of weight, abortion, and death), which are variable from one
      host and one place to another; however, its immunosuppressive effects interfering
      with intercurrent diseases or vaccination campaigns might be its most significant
      and questionable aspect. 

PMID- 24024187
TI  - Development of pineapple microsatellite markers and germplasm genetic diversity
      analysis.
AB  - Two methods were used to develop pineapple microsatellite markers. Genomic
      library-based SSR development: using selectively amplified microsatellite assay,
      86 sequences were generated from pineapple genomic library. 91 (96.8%) of the 94
      Simple Sequence Repeat (SSR) loci were dinucleotide repeats (39 AC/GT repeats and
      52 GA/TC repeats, accounting for 42.9% and 57.1%, resp.), and the other three
      were mononucleotide repeats. Thirty-six pairs of SSR primers were designed; 24 of
      them generated clear bands of expected sizes, and 13 of them showed polymorphism.
      EST-based SSR development: 5659 pineapple EST sequences obtained from NCBI were
      analyzed; among 1397 nonredundant EST sequences, 843 were found containing 1110
      SSR loci (217 of them contained more than one SSR locus). Frequency of SSRs in
      pineapple EST sequences is 1SSR/3.73 kb, and 44 types were found. Mononucleotide,
      dinucleotide, and trinucleotide repeats dominate, accounting for 95.6% in total.
      AG/CT and AGC/GCT were the dominant type of dinucleotide and trinucleotide
      repeats, accounting for 83.5% and 24.1%, respectively. Thirty pairs of primers
      were designed for each of randomly selected 30 sequences; 26 of them generated
      clear and reproducible bands, and 22 of them showed polymorphism. Eighteen pairs
      of primers obtained by the one or the other of the two methods above that showed
      polymorphism were selected to carry out germplasm genetic diversity analysis for
      48 breeds of pineapple; similarity coefficients of these breeds were between 0.59
      and 1.00, and they can be divided into four groups accordingly. Amplification
      products of five SSR markers were extracted and sequenced, corresponding repeat
      loci were found and locus mutations are mainly in copy number of repeats and base
      mutations in the flanking region.

PMID- 24024188
TI  - Image analysis of endosocopic ultrasonography in submucosal tumor using fuzzy
      inference.
AB  - Endoscopists usually make a diagnosis in the submucosal tumor depending on the
      subjective evaluation about general images obtained by endoscopic
      ultrasonography. In this paper, we propose a method to extract areas of
      gastrointestinal stromal tumor (GIST) and lipoma automatically from the
      ultrasonic image to assist those specialists. We also propose an algorithm to
      differentiate GIST from non-GIST by fuzzy inference from such images after
      applying ROC curve with mean and standard deviation of brightness information. In
      experiments using real images that medical specialists use, we verify that our
      method is sufficiently helpful for such specialists for efficient classification
      of submucosal tumors. 

PMID- 24024189
TI  - Meta-analysis of cytokine gene polymorphisms and outcome of heart
      transplantation.
AB  - We performed a systematic review and meta-analysis with the aim of assessing the
      association between cytokine gene polymorphisms and graft rejection in heart
      transplantation. We identified relevant studies from Medline and Embase using
      PubMed and Ovid search engines, respectively. Allele frequencies and allele and
      genotypic effects were pooled. Heterogeneity and publication bias were explored.
      Four to 5 studies were included in pooling of 3 gene polymorphisms. The
      prevalences of the minor alleles for TNF alpha -308, TGF beta 1-c10, and TGF beta
      1-c25 were 0.166 (95% CI: 0.129, 0.203), 0.413 (95% CI: 0.363, 0.462), and 0.082
      (95% CI: 0.054, 0.111) in the control groups, respectively. Carrying the A allele
      for the TNF alpha -308 had 18% (95% CI of OR: 0.46, 3.01) increased risk, but
      this was not significant for developing graft rejection than the G allele.
      Conversely, carrying the minor alleles for both TGF beta 1-c10 and c25 had
      nonsignificantly lower odds of graft rejection than major alleles, with the
      pooled ORs of 0.87 (95% CI: 0.65, 1.18) and 0.70 (95% CI: 0.40, 1.23),
      respectively. There was no evidence of publication bias for all poolings. An
      updated meta-analysis is required when more studies are published to increase the
      power of detection for the association between these polymorphisms and allograft
      rejection. 

PMID- 24024190
TI  - Mediterranean spotted fever in southeastern Romania.
AB  - Although cases of Mediterranean spotted fever (MSF) have been reported for
      decades in southeastern Romania, there are few published data. We retrospectively
      studied 339 patients, diagnosed with MSF at the National Institute of Infectious
      Diseases "Prof. Dr. Matei Bals" between 2000 and 2011, in order to raise
      awareness about MSF in certain regions of Romania. According to the Raoult
      diagnostic criteria 171 (50.4%) had a score >25 points. Mean age was 52.5 years.
      One hundred and fifty-five (90.6%) patients were from Bucharest and the
      surrounding region. Almost all patients presented with fever (99.4%) and rash
      (98.2%), and 57.9% had evidence of a tick bite. There were no recorded deaths.
      Serologic diagnosis was made by indirect immunofluorescence assay. Of the 171
      patients, serology results for R. conorii were available in 147. One hundred and
      twenty-three (83.7%) of them had a titer IgG >=1:160 or a fourfold increase in
      titer in paired samples. MSF is endemic in southeastern Romania and should be
      considered in patients with fever and rash even in the absence of recognized tick
      exposure. Since the disease is prevalent in areas highly frequented by tourists,
      travel-associated MSF should be suspected in patients with characteristic
      symptoms returning from the endemic area.

PMID- 24024191
TI  - Low rate of detection of mucosal high-risk-type human papillomavirus in Korean
      patients with extragenital Bowen's disease and squamous cell carcinoma,
      especially in digital cases.
AB  - Human papillomavirus (HPV) infection has been demonstrated in some of the
      nonmelanoma skin cancers as well as in precancerous lesions. Multiple infections
      of mucosal high-risk HPV may contribute to the onset of digital Bowen's disease
      through, if any, digital-genital transmission. We screened for the presence of
      the mucosal HPV DNA in patients with extragenital Bowen's disease (n = 30),
      squamous cell carcinoma (n = 11), bowenoid papulosis (n = 9), verrucous carcinoma
      (n = 1), actinic keratosis (n = 5), and basal cell carcinoma (n = 5). We used a
      PANArray HPV Genotyping Chip for high-risk and low-risk mucosal types. Genotyping
      data was confirmed using a conventional direct DNA sequencing method. Two cases
      of extragenital Bowen's disease were positive for types 16 and 33 of mucosal HPV,
      respectively. None of the squamous cell carcinoma cases were positive. Neither
      patients with digital Bowen's disease (n = 5) nor those with squamous cell
      carcinoma (n = 3) showed any mucosal high-risk HPV. Mucosal high-risk HPV DNA was
      confirmed in 5 (55.6%) of the 9 patients with bowenoid papulosis. HPV 16 was most
      prevalent (n = 3), while the DNA of HPVs 35 and 67 was detected in one sample for
      each of the two types. Our study demonstrated that two (6.7%) of the patients
      with 30 extragenital Bowen's disease were positive for types 16 and 33 of mucosal
      HPV, respectively. HPVs belonging to the mucosal high-risk group may participate
      in the development of extragenital Bowen's disease. However, we could not find
      any relationship between the mucosal high-risk HPV and Bowen's disease or
      squamous cell carcinoma in the fingers. 

PMID- 24024192
TI  - Physical activity patterns of acute stroke patients managed in a rehabilitation
      focused stroke unit.
AB  - BACKGROUND: Comprehensive stroke unit care, incorporating acute care and
      rehabilitation, may promote early physical activity after stroke. However,
      previous information regarding physical activity specific to the acute phase of
      stroke and the comprehensive stroke unit setting is limited to one stroke unit.
      This study describes the physical activity undertaken by patients within 14 days
      after stroke admitted to a comprehensive stroke unit. METHODS: This study was a
      prospective observational study. Behavioural mapping was used to determine the
      proportion of the day spent in different activities. Therapist reports were used
      to determine the amount of formal therapy received on the day of observation. The
      timing of commencement of activity out of bed was obtained from the medical
      records. RESULTS: On average, patients spent 45% (SD 25) of the day in some form
      of physical activity and received 58 (SD 34) minutes per day of physiotherapy and
      occupational therapy combined. Mean time to first mobilisation out of bed was 46
      (SD 32) hours post-stroke. CONCLUSIONS: This study suggests that commencement of
      physical activity occurs earlier and physical activity is at a higher level early
      after stroke in this comprehensive stroke unit, when compared to studies of other
      acute stroke models of care.

PMID- 24024193
TI  - Carbon nanofibers have IgE adjuvant capacity but are less potent than nanotubes
      in promoting allergic airway responses.
AB  - There is a growing concern for the possible health impact of nanoparticles. The
      main objective of this study was to investigate the allergy-promoting capacity of
      four different carbon nanofiber (CNF) samples in an injection and an airway mouse
      model of allergy. Secondly, the potency of the CNF was compared to the previously
      reported allergy-promoting capacity of carbon nanotubes (CNT) in the airway
      model. Ultrafine carbon black particles (ufCBP) were used as a positive control.
      Particles were given together with the allergen ovalbumin (OVA) either by
      subcutaneous injection into the footpad or intranasally to BALB/cA mice. After
      allergen booster, OVA-specific IgE, IgG1, and IgG2a in serum were measured. In
      the airway model, inflammation was determined as influx of inflammatory cells
      (eosinophils, neutrophils, lymphocytes, and macrophages) and by mediators (MCP-1
      and TNF-alpha present in bronchoalveolar fluid (BALF)). CNF and CNT both
      increased OVA-specific IgE levels in the two models, but in the airway model, the
      CNT gave a significantly stronger IgE response than the CNF. Furthermore, the CNT
      and not the CNF promoted eosinophil lung inflammation. Our data therefore suggest
      that nanotube-associated properties are particularly potent in promoting allergic
      responses. 

PMID- 24024194
TI  - An efficient ensemble learning method for gene microarray classification.
AB  - The gene microarray analysis and classification have demonstrated an effective
      way for the effective diagnosis of diseases and cancers. However, it has been
      also revealed that the basic classification techniques have intrinsic drawbacks
      in achieving accurate gene classification and cancer diagnosis. On the other
      hand, classifier ensembles have received increasing attention in various
      applications. Here, we address the gene classification issue using RotBoost
      ensemble methodology. This method is a combination of Rotation Forest and
      AdaBoost techniques which in turn preserve both desirable features of an ensemble
      architecture, that is, accuracy and diversity. To select a concise subset of
      informative genes, 5 different feature selection algorithms are considered. To
      assess the efficiency of the RotBoost, other nonensemble/ensemble techniques
      including Decision Trees, Support Vector Machines, Rotation Forest, AdaBoost, and
      Bagging are also deployed. Experimental results have revealed that the
      combination of the fast correlation-based feature selection method with ICA-based
      RotBoost ensemble is highly effective for gene classification. In fact, the
      proposed method can create ensemble classifiers which outperform not only the
      classifiers produced by the conventional machine learning but also the
      classifiers generated by two widely used conventional ensemble learning methods,
      that is, Bagging and AdaBoost. 

PMID- 24024195
TI  - NRAMP1, VDR, HLA-DRB1, and HLA-DQB1 gene polymorphisms in susceptibility to
      tuberculosis among the Chinese Kazakh population: a case-control study.
AB  - BACKGROUND: To explore the potential role of natural-resistance-associated
      macrophage protein 1 (NRAMP1) gene, vitamin D receptor (VDR) gene, (human
      leukocyte antigen, (HLA-DRB1) HLA)-DRB1 gene, and HLA-DQB1 gene polymorphisms in
      susceptibility to tuberculosis (TB) in the Chinese Kazakh population. METHODS: A
      case-control study was performed on the Chinese Kazak population. Genetic
      polymorphisms of NRAMP1 gene (3'UTR) and VDR gene (TaqI and FokI) were analysed
      using polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP) and sequencing analysis in TB patients and healthy controls. Genetic
      polymorphisms of HLA-DRB1 gene and HLA-DQB1 gene in the two groups were detected
      with polymerase chain reaction-sequence-specific primers (PCR-SSPs) technique and
      sequencing analysis. RESULTS: There was statistically significant difference in
      the 3'UTR polymorphism between the TB patients and healthy controls in the
      Chinese Kazak population (P = 0.002; OR = 1.859; 95% CI = 1.182-2.926).
      Significant difference was observed in the FokI polymorphism between the TB
      patients and healthy controls (P = 0.001; OR = 1.530; 95% CI = 1.007-2.325). It
      does not disclose any significant association between the disease and TaqI (P >
      0.05). Alleles HLA-DRB1*04 and HLA-DQB1*0201 occurred more frequently in patients
      than in controls (P = 0.011 and 0.002; OR = 1.889 and 1.802; 95% CI = 1.153-3.095
      and 1.230-2.639, resp.). CONCLUSIONS: Polymorphisms in the NRAMP1 gene, VDR gene,
      HLA-DRB1 gene, and HLA-DQB1 gene are statistically associated with susceptibility
      to TB in the Chinese Kazakh population.

PMID- 24024196
TI  - Bronchial responsiveness in patients with restrictive spirometry.
AB  - BACKGROUND: Improvement in PFT after bronchodilators is characteristic of
      obstructive airway diseases such as COPD. However, improvement in patients with
      restrictive pattern is occasionally seen. We aim to determine the clinical
      significance of a bronchodilator responsive restrictive defect. METHODS: Patients
      with restrictive spirometry and a bronchodilator study were identified at the
      University of Oklahoma and Oklahoma City VAMC between September 2003 and December
      2009. Restriction was defined as a decreased FVC and FEV1, with normal FEV1/FVC.
      Responsiveness to bronchodilators was defined as an improvement in FEV1 and/or
      FVC of at least 12% and 200 mL. Patients with lung volume measurements had their
      clinical and radiographic records reviewed. RESULTS: Twenty-one patients were
      included in the study. Most were current or ex-smokers, with most being on
      bronchodilators. The average FVC and FEV1 were 65 +/- 11% and 62 +/- 10% of the
      predicted, respectively. Most patients (66%) had a normal TLC, averaging 90 +/-
      16% of the predicted. RV, RV/TLC, and the TLC-VA values strongly suggested an
      obstructive defect. CONCLUSIONS: Reversible restrictive pattern on spirometry
      appears to be a variant of obstructive lung disease in which early airway closure
      results in air trapping and low FVC. In symptomatic patients, a therapeutic trial
      of bronchodilators may be beneficial.

PMID- 24024197
TI  - Low-dose-area-constrained helical TomoTherapy-based whole breast radiotherapy and
      dosimetric comparison with tangential field-in-field IMRT.
AB  - BACKGROUND AND PURPOSE: To present a novel helical TomoTherapy-based method for
      whole breast radiotherapy that has better dosimetry and also has acceptable low
      dose regions for lungs, heart, and contralateral breast compared with tangential
      field-in-field IMRT (FIF-IMRT). MATERIAL AND METHODS: Ten patients with left-side
      breast cancer were planned with low-dose-area-constrained helical TomoTherapy
      (LDC-HT) and FIF-IMRT. Dosimetry was compared for all techniques. RESULTS:
      Coverage of the whole breast was adequate with both techniques. Homogeneity index
      (HI) and conformity index (CI) were better with LDC-HT. LDC-HT showed dosimetry
      advantages over FIF-IMRT for ipsilateral lung and heart in not only high-dose
      levels but also in low-dose levels such as V(10 Gy) and V(5 Gy). For
      contralateral lung, both techniques can provide good protection, although the
      mean dose of LDC-HT is higher than that of FIF-IMRT. CONCLUSIONS: With LDC-HT, we
      obtained adequate target coverage, better HI and CI of target volume, better
      sparing of organs at risk, and acceptably low-dose areas compared with FIF-IMRT.
      LDC-HT could be a feasible method in whole breast radiotherapy. Clinical benefits
      of LDC-HT need further investigation.

PMID- 24024198
TI  - Novel GUCA1A mutations suggesting possible mechanisms of pathogenesis in cone,
      cone-rod, and macular dystrophy patients.
AB  - Here, we report two novel GUCA1A (the gene for guanylate cyclase activating
      protein 1) mutations identified in unrelated Spanish families affected by
      autosomal dominant retinal degeneration (adRD) with cone and rod involvement. All
      patients from a three-generation adRD pedigree underwent detailed ophthalmic
      evaluation. Total genome scan using single-nucleotide polymorphisms and then the
      linkage analysis were undertaken on the pedigree. Haplotype analysis revealed a
      55.37 Mb genomic interval cosegregating with the disease phenotype on chromosome
      6p21.31-q15. Mutation screening of positional candidate genes found a
      heterozygous transition c.250C>T in exon 4 of GUCA1A, corresponding to a novel
      mutation p.L84F. A second missense mutation, c.320T>C (p.I107T), was detected by
      screening of the gene in a Spanish patients cohort. Using bioinformatics
      approach, we predicted that either haploinsufficiency or dominant-negative effect
      accompanied by creation of a novel function for the mutant protein is a possible
      mechanism of the disease due to c.250C>T and c.320T>C. Although additional
      functional studies are required, our data in relation to the c.250C>T mutation
      open the possibility that transacting factors binding to de novo created
      recognition site resulting in formation of aberrant splicing variant is a disease
      model which may be more widespread than previously recognized as a mechanism
      causing inherited RD.

PMID- 24024199
TI  - Modulation of vasodilator response via the nitric oxide pathway after acute
      methyl mercury chloride exposure in rats.
AB  - Mercury exposure induces endothelial dysfunction leading to loss of endothelium
      dependent vasorelaxation due to decreased nitric oxide (NO) bioavailability via
      increased oxidative stress. Our aim was to investigate whether acute treatment
      with methyl mercury chloride changes the endothelium-dependent vasodilator
      response and to explore the possible mechanisms behind the observed effects.
      Wistar rats were treated with methyl mercury chloride (5 mg/kg, po.). The methyl
      mercury chloride treatment resulted in an increased aortic vasorelaxant response
      to acetylcholine (ACh). In methyl-mercury-chloride-exposed rats, the % change in
      vasorelaxant response of ACh in presence of Nomega-Nitro-L-arginine methyl ester
      hydrochloride (L-NAME; 10(-4) M) was significantly increased, and in presence of
      glybenclamide (10(-5) M), the response was similar to that of untreated rats,
      indicating the involvement of NO and not of endothelium-derived hyperpolarizing
      factor (EDHF). In addition, superoxide dismutase (SOD) + catalase treatment
      increased the NO modulation of vasodilator response in methyl-mercury-chloride
      exposed rats. Our results demonstrate an increase in the vascular reactivity to
      ACh in aorta of rats acutely exposed to methyl mercury chloride. Methyl mercury
      chloride induces nitric oxide synthase (NOS) and increases the NO production
      along with inducing oxidative stress without affecting the EDHF pathway.

PMID- 24024200
TI  - A novel multilayered multidisk oral tablet for chronotherapeutic drug delivery.
AB  - A Multilayered Multidisk Tablet (MLMDT) comprising two drug-loaded disks
      enveloped by three drug-free barrier layers was developed for use in
      chronotherapeutic disorders, employing two model drugs, theophylline and
      diltiazem HCl. The MLMDT was designed to achieve two pulses of drug release
      separated by a lag phase. The polymer disk comprised hydroxyethylcellulose (HEC)
      and ethylcellulose (EC) granulated using an aqueous dispersion of EC. The
      polymeric barrier layers constituted a combination of pectin/Avicel (PBL) (1st
      barrier layer) and hydroxypropylmethylcellulose (HPMC) (HBL1 and HBL2) as the 2nd
      and 3rd barrier layers, respectively. Sodium bicarbonate was incorporated into
      the diltiazem-containing formulation for delayed drug release. Erosion and
      swelling studies confirmed the manner in which the drug was released with
      theophylline formulations exhibiting a maximum swelling of 97% and diltiazem
      containing formulations with a maximum swelling of 119%. FTIR spectra displayed
      no interactions between drugs and polymers. Molecular mechanics simulations were
      undertaken to predict the possible orientation of the polymer morphologies most
      likely affecting the MLMDT performance. The MLMDT provided two pulses of drug
      release, separated by a lag phase, and additionally it displayed desirable
      friability, hardness, and uniformity of mass indicating a stable formulation that
      may be a desirable candidate for chronotherapeutic drug delivery. 

PMID- 24024201
TI  - ISG15 inhibits IFN-alpha-resistant liver cancer cell growth.
AB  - Hepatocellular carcinoma (HCC) is one of the most prevalent tumors worldwide.
      Interferon-alpha (IFN-alpha) has been widely used in the treatment of HCC, but
      patients eventually develop resistance. ISG15 ubiquitin-like modifier (ISG15) is
      a ubiquitin-like protein transcriptionally regulated by IFN-alpha which shows
      antivirus and antitumor activities. However, the exact role of ISG15 is unknown.
      In the present study, we showed that IFN-alpha significantly induced ISG15
      expression but failed to induce HepG2 cell apoptosis, whereas transient
      overexpression of ISG15 dramatically increased HepG2 cell apoptosis. ISG15
      overexpression increased overall protein ubiquitination, which was not observed
      in cells with IFN-alpha-induced ISG15 expression, suggesting that IFN-alpha
      treatment not only induced the expression of ISG15 but also inhibited ISG15
      mediated ubiquitination. The tumor suppressor p53 and p21 proteins are the key
      regulators of cell survival and death in response to stress signals such as DNA
      damage. We showed that p53 or p21 is only up regulated in HepG2 cells ectopically
      expressing ISG15, but not in the presence of IFN-alpha-induced ISG15. Our results
      suggest that ISG15 overexpression could be developed into a powerful gene
      therapeutic tool for treating IFN-alpha-resistant HCC.

PMID- 24024202
TI  - Neurogenesis and increase in differentiated neural cell survival via
      phosphorylation of Akt1 after fluoxetine treatment of stem cells.
AB  - Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI). Its action
      is possibly through an increase in neural cell survival. The mechanism of
      improved survival rate of neurons by FLX may relate to the overexpression of some
      kinases such as Akt protein. Akt1 (a serine/threonine kinase) plays a key role in
      the modulation of cell proliferation and survival. Our study evaluated the
      effects of FLX on mesenchymal stem cell (MSC) fate and Akt1 phosphorylation
      levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain
      reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, and beta
      tubulin were detected after neurogenesis as neural markers. Ten MU M of FLX
      upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also
      FLX did increase viability of these MSCs. Continuous FLX treatment after
      neurogenesis elevated the survival rate of differentiated neural cells probably
      by enhanced induction of Akt1 phosphorylation. This study addresses a novel role
      of FLX in neurogenesis and differentiated neural cell survival that may
      contribute to explaining the therapeutic action of fluoxetine in regenerative
      pharmacology.

PMID- 24024203
TI  - The usefulness of confusion, urea, respiratory rate, and shock index or adjusted
      shock index criteria in predicting combined mortality and/or ICU admission
      compared to CURB-65 in community-acquired pneumonia.
AB  - BACKGROUND AND OBJECTIVES: The study aims to assess the usefulness of age
      independent criteria CURSI and temperature adjusted CURSI (CURASI) compared to
      CURB-65 in predicting community-acquired pneumonia (CAP) mortality. The criteria,
      CRSI and CRASI, were adapted for use in primary care and compared to CRB-65.
      METHODS: A retrospective analysis of a prospectively identified cohort of
      community-acquired pneumonia inpatients was conducted. Outcomes were (1)
      mortality and (2) mortality and/or ICU admission within six weeks. RESULTS: 95
      patients (median age = 61 years) were included. All three criteria had similar
      sensitivity in predicting mortality alone, with CURB-65 having slightly higher
      specificity. When predicting mortality and/or intensive care admission,
      CURSI/CURASI showed higher sensitivity and slightly lower specificity. CRSI and
      CRASI had higher sensitivity and lower specificity when compared with CRB-65 for
      predicting both primary and secondary outcomes. Results for both analyses had P
      values >0.05. CONCLUSIONS: In a cohort of younger patients CURSI and adjusted
      CURSI perform at least as well as CURB-65, with a similar trend for CRSI and
      adjusted CRSI compared to CRB-65. Further studies are needed in different age
      groups and in primary and secondary care settings.

PMID- 24024204
TI  - Hypoxic pulmonary vasoconstriction in humans.
AB  - Hypoxic pulmonary vasoconstriction is the elegant theory put forward more than
      six decades ago to explain regional variations in perfusion within the lung in
      certain animal species in response to localised restrictions in oxygenation.
      Although considerable progress has been made to describe the phenomenon at the
      macroscopic level and explain it at the microscopic level, we are far from a
      universal agreement about the process in humans. This review attempts to
      highlight some of the important evidence bases of hypoxic pulmonary
      vasoconstriction in humans and the significant gaps in our knowledge that would
      need bridging. 

PMID- 24024205
TI  - Maternal deaths in NSW (2000-2006) from nonmedical causes (suicide and trauma) in
      the first year following birth.
AB  - INTRODUCTION: Trauma, including suicide, accidental injury, motor traffic
      accidents, and homicides, accounts for 73% of all maternal deaths (early and
      late) in NSW annually. Late maternal deaths are underreported and are not as well
      documented or acknowledged as early deaths. METHODS: Linked population datasets
      from births, hospital admissions, and death registrations were analysed for the
      period from 1 July 2000 to 31 December 2007. RESULTS: There were 552,901 births
      and a total of 129 maternal deaths. Of these deaths, 37 were early deaths (early
      MMR of 6.7/100,000) and 92 occurred late (late MMR of 16.6/100,000). Sixty-seven
      percent of deceased women had a mental health diagnosis and/or a mental health
      issue related to substance abuse noted. A notable peak in deaths appeared to
      occur from 9 to 12 months following birth with the odds ratio of a woman dying of
      nonmedical causes within 9-12 months of birth being 3.8 (95% CI 1.55-9.01) when
      compared to dying within the first 3 months following birth. CONCLUSION:
      Perinatal services are often constructed to provide short-term support. Long-term
      identification and support of women at particular risk of maternal death due to
      suicide and trauma in the first year following birth may help lower the incidence
      of late maternal deaths.

PMID- 24024206
TI  - Sphingomyelinase activity of Trichomonas vaginalis extract and subfractions.
AB  - Trichomoniasis is one of the most common acute sexually transmitted curable
      diseases, and it is disseminated worldwide generating more than 170 million cases
      annually. Trichomonas vaginalis is the parasite that causes trichomoniasis and
      has the ability to destroy cell monolayers of the vaginal mucosa in vitro.
      Sphingomyelinases (SMase) are enzymes that catalyze the hydrolysis of
      sphingomyelin into ceramide and phosphorylcholine. Ceramide appears to be a
      second messenger lipid in programmed apoptosis, cell differentiation, and cell
      proliferation. Sphingomyelinase is probably a major source of ceramide in cells.
      Signal transduction mediated by ceramide leads cells to produce cytokine induced
      apoptosis during several inflammatory responses. SMase are also relevant toxins
      in several microorganisms. The main objective of this research is to identify
      SMase activity of T. vaginalis in the total extract (TE), P30, and S30
      subfractions from brooked trophozoites. It was found that these fractions of T.
      vaginalis have SMase activity, which comes principally from P30 subfraction and
      was mainly type C. Enzymatic activity of SMase increased linearly with time and
      is pH dependent with two peaks by pH 5.5 and pH 7.5. The addition of manganese to
      the reaction mixture increased the SMase activity by 1.97. 

PMID- 24024208
TI  - Analysis of IL-1 beta release from cryopreserved pooled lymphocytes in response
      to lipopolysaccharide and lipoteichoic acid.
AB  - Pyrogens are heterogeneous group of fever-inducing substances derived from Gram
      positive and Gram-negative bacteria, fungi, and viruses. They incite immune
      response by producing endogenous pyrogens such as prostaglandins and other
      proinflammatory cytokines like IL-1beta, IL-6, and TNF-alpha. The present study
      was to analyze the influence of cryopreservation in IL-1beta release, a marker
      for inflammatory response from human lymphocytes, in response to exogenous
      pyrogenic stimulants. Lymphocytes isolated from pooled blood of multiple healthy
      individuals were cryopreserved in DMSO and glycerol for periods of 7, 14, 30, and
      60 days and were challenged with LPS and LTA in vitro. The inflammatory cytokine,
      IL-1beta release, was measured by ELISA method. It was observed that the release
      of IL-1beta increases instantaneously after the initiation of incubation and
      reaches a maximum at 3 to 5 hours and then gradually decreases and gets
      stabilized for both pyrogens. Moreover it was also observed that the effect of
      cryoprotectants, DMSO (10%) and glycerol (10%), showed almost similar results for
      short-term storage, but DMSO-preserved lymphocytes yielded a better viability for
      long-term storage. Thus, the isolated cryopreserved lymphocytes system can be a
      promising approach for the total replacement/alteration to animal experimentation
      for pyrogenicity evaluation.

PMID- 24024207
TI  - The immunobiology of prostanoid receptor signaling in connecting innate and
      adaptive immunity.
AB  - Prostanoids, including prostaglandins (PGs), thromboxanes (TXs), and
      prostacyclins, are synthesized from arachidonic acid (AA) by the action of
      Cyclooxygenase (COX) enzymes. They are bioactive inflammatory lipid mediators
      that play a key role in immunity and immunopathology. Prostanoids exert their
      effects on immune and inflammatory cells by binding to membrane receptors that
      are widely expressed throughout the immune system and act at multiple levels in
      innate and adaptive immunity. The immunoregulatory role of prostanoids results
      from their ability to regulate cell-cell interaction, antigen presentation,
      cytokine production, cytokine receptor expression, differentiation, survival,
      apoptosis, cell-surface molecule levels, and cell migration in both autocrine and
      paracrine manners. By acting on immune cells of both systems, prostanoids and
      their receptors have great impact on immune regulation and play a pivotal role in
      connecting innate and adaptive immunity. This paper focuses on the immunobiology
      of prostanoid receptor signaling because of their potential clinical relevance
      for various disorders including inflammation, autoimmunity, and tumorigenesis. We
      mainly discuss the effects of major COX metabolites, PGD2, PGE2, their signaling
      during dendritic cell (DC)-natural killer (NK) reciprocal crosstalk, DC-T cell
      interaction, and subsequent consequences on determining crucial aspects of innate
      and adaptive immunity in normal and pathological settings. 

PMID- 24024209
TI  - Levels of key enzymes of methionine-homocysteine metabolism in preeclampsia.
AB  - OBJECTIVE: To evaluate the role of key enzymes in the methionine-homocysteine
      metabolism (MHM) in the physiopathology of preeclampsia (PE). METHODS: Plasma and
      placenta from pregnant women (32 controls and 16 PE patients) were analyzed after
      informed consent. Protein was quantified by western blot. RNA was obtained with
      RNA purification kit and was quantified by reverse transcritase followed by real
      time PCR (RT-qPCR). Identification of the C677T and A1298C
      methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms
      (SNPs) and A2756G methionine synthase (MTR) SNP was performed using PCR followed
      by a high-resolution melting (HRM) analysis. S-adenosyl methionine (SAM) and S
      adenosyl homocysteine (SAH) were measured in plasma using high-performance liquid
      chromatography-tandem mass spectrometry (HPLC/MS/MS). The SNP association
      analysis was carried out using Fisher's exact test. Statistical analysis was
      performed using a Mann-Whitney test. RESULTS: RNA expression of MTHFR and MTR was
      significantly higher in patients with PE as compared with controls. Protein, SAM,
      and SAH levels showed no significant difference between preeclamptic patients and
      controls. No statistical differences between controls and PE patients were
      observed with the different SNPs studied. CONCLUSION: The RNA expression of MTHFR
      and MTR is elevated in placentas of PE patients, highlighting a potential
      compensation mechanism of the methionine-homocysteine metabolism in the
      physiopathology of this disease.

PMID- 24024210
TI  - The SDF-1alpha3'A genetic variation is correlated with susceptibility of asthma
      in Iranian patients.
AB  - BACKGROUND AND AIM: Chemokine/receptor axis is a predominant actor of clinical
      disorders. They are key factors of pathogenesis of almost all clinical situations
      including asthma. Correspondingly, CXCL12 is involved in the immune responses.
      Therefore, this study was designed to explore the association between gene
      polymorphism at position +801 of CXCL12, known as SDF-1alpha3'A, and
      susceptibility to asthma in Iranian patients. MATERIAL AND METHODS: In this
      experimental study, samples were taken from 162 asthma patients and 189 healthy
      controls on EDTA. DNA was extracted and analyzed for CXCL12 polymorphisms using
      PCR-RLFP. The demographic information was also collected in parallel with the
      experimental part of the study by a questionnaire which was designed specifically
      for this study. FINDINGS: Our results indicated a significant difference (P <
      0.0001) between the A/A, A/G, and G/G genotypes and A and G alleles of
      polymorphisms at position +801 of CXCL12. We also showed an elevated level of
      CXCL12 circulating level in Iranian asthma patients. CONCLUSION: Our findings
      suggest that SDF-1alpha3'A (CXCL12) polymorphism plays a role in pathogenesis of
      asthma. It can also be concluded that circulatory level of CXCL12 presumably can
      be used as one of the pivotal biological markers in diagnosis of asthma.

PMID- 24024211
TI  - Anthelmintic effects of alkylated diamines and amino alcohols against Schistosoma
      mansoni.
AB  - Polyamines are substances involved in many aspects of cell growth, division, and
      differentiation. Because of the metabolic differences between host cells and
      parasite cells, polyamine metabolism has been considered as a potential target
      for the chemotherapy of parasitic diseases. The aim of this work was to evaluate
      the schistosomicidal activity of different N-alkylated diamines (3a-3h), amino
      alcohols (4a-4d), and glycosylated amino alcohols (10a-10d). Compounds were
      prepared by synthetic methods and submitted to in vitro evaluation against adult
      worms of Schistosoma mansoni. At 100 MUM, 3b, 3e, and 3h as well as 4a, 4b, 4d,
      10a, 10b, and 10d resulted in 100% mortality of adult schistosomes. Compound 3d
      (12.5 to 100 MUM) caused the death of 100% of both male and female adult
      schistosomes, while 3f (12.5 to 100 MUM) resulted in 100% mortality of only male
      adult worms, whereas no mortality in female worms was observed. Compounds 3d and
      3f were also able to reduce viability and decrease production of developed eggs
      in comparison with the negative control group. Diamines 3d and 3f may represent
      useful lead compounds for further optimization in order to develop new
      schistosomicidal agents.

PMID- 24024212
TI  - Dissolution of silver nanowires and nanospheres dictates their toxicity to
      Escherichia coli.
AB  - Silver nanoparticles are extensively used in antibacterial applications. However,
      the mechanisms of their antibacterial action are not yet fully explored. We
      studied the solubility-driven toxicity of 100 * 6100 nm (mean primary diameter *
      length) silver nanowires (NWs) to recombinant bioluminescent Escherichia coli as
      a target representative of enteric pathogens. The bacteria were exposed to silver
      nanostructures in water to exclude the speciation-driven alterations. Spherical
      silver nanoparticles (83 nm mean primary size) were used as a control for the
      effect of NPs shape. Toxicity of both Ag NWs and spheres to E. coli was observed
      at similar nominal concentrations: the 4h EC50 values, calculated on the basis of
      inhibition of bacterial bioluminescence, were 0.42 +/- 0.06 and 0.68 +/- 0.01 mg
      Ag/L, respectively. Dissolution and bioavailability of Ag from NWs and
      nanospheres, analyzed with AAS or Ag-sensor bacteria, respectively, suggested
      that the toxic effects were caused by solubilized Ag(+) ions. Moreover, the
      antibacterial activities of Ag NWs suspension and its ultracentrifuged particle
      free supernatant were equal. The latter indicated that the toxic effects of ~80
      100 nm Ag nanostructures to Escherichia coli were solely dependent on their
      dissolution and no shape-induced/related effects were observed. Yet, additional
      nanospecific effects could come into play in case of smaller nanosilver
      particles.

PMID- 24024213
TI  - Evaluation of a thiolated chitosan scaffold for local delivery of BMP-2 for
      osteogenic differentiation and ectopic bone formation.
AB  - Thiolated chitosan (Thio-CS) is a well-established pharmaceutical excipient for
      drug delivery. However, its use as a scaffold for bone formation has not been
      investigated. The aim of this study was to evaluate the potential of Thio-CS in
      bone morphogenetic protein-2 (BMP-2) delivery and bone formation. In vitro study
      showed that BMP-2 interacted with the Thio-CS and did not affect the swelling
      behavior. The release kinetics of BMP-2 from the Thio-CS was slightly delayed
      (70%) within 7 days compared with that from collagen gel (Col-gel, 85%), which is
      widely used in BMP-2 delivery. The BMP-2 released from Thio-CS increased
      osteoblastic cell differentiation but did not show any cytotoxicity until 21
      days. Analysis of the in vivo ectopic bone formation at 4 weeks of
      posttransplantation showed that use of Thio-CS for BMP-2 delivery induced more
      bone formation to a greater extent (1.8 fold) than that of Col-gel. However, bone
      mineral density in both bones was equivalent, regardless of Thio-CS or Col-gel
      carrier. Taken together, Thio-CS system might be useful for delivering osteogenic
      protein BMP-2 and present a promising bone regeneration strategy. 

PMID- 24024214
TI  - Serum brain-derived neurotrophic factor levels in different neurological
      diseases.
AB  - Consistent evidence indicates the involvement of the brain-derived neurotrophic
      factor (BDNF) in neurodegenerative disorders such as Alzheimer's disease (AD) and
      Parkinson's disease (PD). In the present study, we compared serum BDNF in 624
      subjects: 266 patients affected by AD, 28 by frontotemporal dementia (FTD), 40 by
      Lewy body dementia (LBD), 91 by vascular dementia (VAD), 30 by PD, and 169
      controls. Our results evidenced lower BDNF serum levels in AD, FTD, LBD, and VAD
      patients (P < 0.001) and a higher BDNF concentration in patients affected by PD
      (P = 0.045). Analyses of effects of pharmacological treatments suggested
      significantly higher BDNF serum levels in patients taking mood
      stabilizers/antiepileptics (P = 0.009) and L-DOPA (P < 0.001) and significant
      reductions in patients taking benzodiazepines (P = 0.020). In conclusion, our
      results support the role of BDNF alterations in neurodegenerative mechanisms
      common to different forms of neurological disorders and underline the importance
      of including drug treatment in the analyses to avoid confounding effects. 

PMID- 24024215
TI  - No association of IFNG+874T/A SNP and NOS2A-954G/C SNP variants with nitric oxide
      radical serum levels or susceptibility to tuberculosis in a Brazilian population
      subset.
AB  - Tuberculosis (TB) is one of the most common infectious diseases in the world.
      Mycobacterium tuberculosis infection leads to pulmonary active disease in
      approximately 5-10% of exposed individuals. Both bacteria- and host-related
      characteristics influence latent infection and disease. Host genetic
      predisposition to develop TB may involve multiple genes and their polymorphisms.
      It was reported previously that interferon gamma (IFN-gamma) and nitric oxide
      synthase 2 (NOS2) are expressed on alveolar macrophages from TB patients and are
      responsible for bacilli control; thus, we aimed this study at genotyping single
      nucleotide polymorphisms IFNG+874T/A SNP and NOS2A-954G/C SNP to estimate their
      role on TB susceptibility and determine whether these polymorphisms influence
      serum nitrite and NOx(-) production. This case-control study enrolled 172 TB
      patients and 179 healthy controls. Neither polymorphism was associated with
      susceptibility to TB. NOS2A-954G/C SNP was not associated with serum levels of
      nitrite and NOx(-). These results indicate that variants of IFNG+874T/A SNP and
      NOS2A-954G/C SNP do not influence TB susceptibility or the secretion of nitric
      oxide radicals in the study population.

PMID- 24024217
TI  - Suicide-related contacts--experience in general practice.
AB  - We examined the rate of suicide-related contacts (SRCs) in general practice
      between April 1998 and March 2013. We defined an SRC as a general practitioner
      (GP)-patient encounter where suicide ideation or attempt (International
      Classification of Primary Care 2nd edn, code P77) was recorded as either a
      problem under management or a patient's reason for encounter (RFE). Between 1998
      and 2013, 14 793 GPs participated in BEACH (Bettering the Evaluation and Care of
      Health) and recorded details of 1 479 300 encounters with patients. There were
      406 SRC encounters. Most of these were identified through the patient's RFE and
      not by the GP's label of a problem managed at the encounter. Depression was the
      most frequent problem managed at encounters where suicidal ideation or attempt
      was a patient's RFE. This suggests that suicide is often subsumed in the
      'depression' label and that we are only identifying a subset of encounters with
      patients who are dealing with suicidal thoughts. 

PMID- 24024218
TI  - Obsessive-compulsive disorder--the role of the GP.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a mental illness that causes
      high levels of morbidity and is commonly associated with long delays between
      onset of symptoms and access to diagnosis and treatment. OBJECTIVE: To address
      some of the key clinical questions about detecting and managing OCD from the
      general practice perspective. DISCUSSION: General practitioners play a crucial
      role in recognising OCD, in facilitating timely access to evidence-based
      therapies and providing ongoing follow-up and support. Exposure and response
      prevention, and selective serotonin re-uptake inhibitors have the strongest
      evidence for efficacy in patients with OCD.

PMID- 24024219
TI  - Early response to psychological trauma--what GPs can do.
AB  - BACKGROUND: There is a high prevalence of psychological trauma exposure among
      primary care patients. General practitioners are well placed to provide
      appropriate support for patients coping with trauma. OBJECTIVE: This article
      outlines an evidence-based early response to psychological trauma. DISCUSSION:
      Psychological first aid is the preferred approach in providing early assistance
      to patients who have experienced a traumatic event. General practitioners can be
      guided by five empirically derived principles in their early response: promoting
      a sense of safety, calming, self efficacy, connectedness and hope. Structured
      psychological interventions, including psychological debriefing, are not
      routinely recommended in the first few weeks following trauma exposure. General
      practitioner self care is an important aspect of providing post-trauma patient
      care.

PMID- 24024216
TI  - Emerging metabolic targets in the therapy of hematological malignancies.
AB  - During the last decade, the development of anticancer therapies has focused on
      targeting neoplastic-related metabolism. Cancer cells display a variety of
      changes in their metabolism, which enable them to satisfy the high bioenergetic
      and biosynthetic demands for rapid cell division. One of the crucial alterations
      is referred to as the "Warburg effect", which involves a metabolic shift from
      oxidative phosphorylation towards the less efficient glycolysis, independent of
      the presence of oxygen. Although there are many examples of solid tumors having
      altered metabolism with high rates of glucose uptake and glycolysis, it was only
      recently reported that this phenomenon occurs in hematological malignancies. This
      review presents evidence that targeting the glycolytic pathway at different
      levels in hematological malignancies can inhibit cancer cell proliferation by
      restoring normal metabolic conditions. However, to achieve cancer regression,
      high concentrations of glycolytic inhibitors are used due to limited solubility
      and biodistribution, which may result in toxicity. Besides using these inhibitors
      as monotherapies, combinatorial approaches using standard chemotherapeutic agents
      could display enhanced efficacy at eradicating malignant cells. The
      identification of the metabolic enzymes critical for hematological cancer cell
      proliferation and survival appears to be an interesting new approach for the
      targeted therapy of hematological malignancies. 

PMID- 24024220
TI  - Bipolar disorder.
AB  - BACKGROUND: Bipolar disorder affects about 1% of Australians and impacts severely
      on relationships, careers and general functional capacity. General practitioners
      are central in the management of patients with bipolar disorder. OBJECTIVE: To
      update clinicians on the recognition, diagnosis and management of bipolar
      disorder in light of recent research. DISCUSSION: There is growing concern about
      the over-diagnosis of bipolar disorder, and increasing evidence that bipolar
      depression may present differently to unipolar depression. Antipsychotics are the
      initial agents of choice for the acute treatment of mania. For preventive
      treatment, lithium and atypical antipsychotics have the strongest evidence base.
      Lithium has been shown to be more effective than valproate. The main effect of
      lithium and most of the atypical antipsychotics is on prevention of manic
      relapse; only olanzapine and quetiapine also protect against depression.
      Lamotrigine is an agent with evidence for prevention of depressive relapse, but
      have minimal activity against mania. The role of antidepressants remains
      contentious, while there is strong support for quetiapine. Finally, there is
      growing evidence from randomised controlled trials of the benefit of
      psychological therapies in conjunction with medications.

PMID- 24024221
TI  - Selective serotonin re-uptake inhibitors--a review of the side effects in
      adolescents.
AB  - BACKGROUND: Selective serotonin re-uptake inhibitors (SSRIs) are prescribed by
      general practitioners (GPs) for adolescents. GPs' prescribing patterns for SSRIs
      changed following warnings issued by United Kingdom and United States drug
      advisory bodies on the use of antidepressants in children and adolescents in 2003
      and 2004, respectively. Recent studies shed further light on the safety profile
      of SSRIs with adolescents. OBJECTIVE: To provide a narrative review of the
      physical and psychiatric side effects of SSRIs as reported by adolescents. To
      provide GPs with practical advice regarding the prevalence and nature of side
      effects of SSRIs when prescribed for adolescents. DISCUSSION: The research
      literature suggests that adolescents taking SSRIs are at a small, but increased,
      risk of suicidal thoughts and behaviours. The prescribing GP needs to be aware of
      a number of potential side effects and interactions. Monitoring for common
      physical side effects and possible emerging suicidal ideas and behaviours,
      especially early in treatment, is recommended.

PMID- 24024222
TI  - Emerging psychosis in adolescents--a practical guide.
AB  - BACKGROUND: Emerging psychosis is a challenging presentation for the general
      practitioner as there is disagreement in the literature about classification and
      appropriate treatment protocols. OBJECTIVE: This paper highlights three main
      issues in primary care: recognising early signs of emerging psychosis, and how
      and when to refer patients; complexities associated with comorbid substance use;
      and management when the patient is referred back to primary care in the post
      acute phase. DISCUSSION: Emerging psychosis is a complex presentation that
      warrants a considered approach right from the initial assessment. This paper
      emphasises the rationale for 'watchful waiting' in the interest of diagnostic
      certainty before potentially harmful treatments are commenced. There are also
      guidelines for a balanced approach to management, where engagement with the
      patient, monitoring medication effects and preventing relapse are the main aims.

PMID- 24024223
TI  - Pulmonary embolism: assessment and imaging.
AB  - It is estimated that there are approximately 17,000 new cases of venous
      thromboembolism (VTE) in Australia per year. Pulmonary embolism (PE) accounts for
      about 40% of these events, and is an important preventable cause of morbidity and
      potentially death. Clinical symptoms of PE are non-specific and can be mild
      (Table 1). Primary care doctors need a robust system to exclude PE as they will
      most often be the first port of call for patients with PE symptoms.

PMID- 24024224
TI  - ACEIs for cardiovascular risk reduction--have we taken our eye off the ball?
AB  - BACKGROUND: Hypertensive patients have an increased risk of cardiovascular (CV)
      events. There is debate whether angiotensin converting enzyme inhibitors (ACEIs)
      and angiotensin receptor blockers (ARBs) offer similar reductions in CV risk.
      OBJECTIVE: This article discusses some of the recent evidence for the prevention
      of CV events and mortality with ACEIs and ARBs, and the rationale for using an
      ACEI as the preferred agent for comprehensive CV risk reduction in specific
      patient populations. DISCUSSION: ACEIs and ARBs are structurally and functionally
      very different agents; they are not interchangeable. Prescriptions for ARBs are
      increasing in Australia. However, clinical trial evidence suggests possible
      advantages of ACEIs over ARBs, particularly in terms of survival benefit. Many
      patients with hypertension have other CV risk factors that may affect medication
      choice. The aim of treatment should not be just to lower blood pressure, but to
      reduce absolute CV risk.

PMID- 24024225
TI  - Sudden onset hearing loss--causes, investigations and management.
AB  - BACKGROUND: Sudden onset hearing loss (SOHL) has a number of causes, ranging from
      the simple and reversible to the profound and permanent. The sequelae of a sudden
      loss of hearing can be significant. OBJECTIVE: This article seeks to address the
      various aetiologies of SOHL, how they can be diagnosed at the earliest
      opportunity, and outlines the methods of investigation and management.
      DISCUSSION: SOHL causes great concern for the patient. It is when there is a 30
      dB or greater hearing loss over less than 72 hours. History and examination, with
      discerning use of investigations, can identify whether the hearing loss is of
      conductive or sensorineural origin; and those individuals who have a potentially
      reversible hearing loss that can be addressed quickly and in an appropriate
      fashion. However, in the majority of cases of sudden sensorineural hearing loss
      (SSNHL), no cause is identified and it is considered idiopathic SSNHL. In these
      patients, high dose oral prednisolone may improve hearing outcome, particularly
      if started early.

PMID- 24024226
TI  - Self-monitoring blood glucose--non-insulin-treated type 2 diabetes in Australian
      general practice.
AB  - BACKGROUND: Benefits of self-monitoring blood glucose (SMBG) in non-insulin
      treated type 2 diabetes (T2D) are questionable. We investigated proportions of
      general practitioner (GP) patients who self-monitor, and associations between
      SMBG, glycosylated haemoglobin (HbA1c) and body mass index (BMI). METHODS: Sub
      studies of the Bettering the Evaluation and Care of Health (BEACH) program,
      involving 5 730 patients from 194 GPs. Outcomes Type 2 diabetes prevalence;
      HbA1c; BMI; blood glucose (BG) monitoring routine. RESULTS: Prevalence of non
      insulin-treated T2D was 6.7%. Mean HbA1c level was 7.1%. Almost half (47.5%) of
      T2D patients were obese compared with 26.7% of patients at all BEACH encounters
      in 2011-2012. Of 344 non-insulin-treated T2D patients, 79.4% self-monitored
      fasting BG and 69.7% of 314 self-monitored post-prandial BG. For both groups,
      mean HbA1c was significantly higher for those who tested daily than for those who
      never tested. CONCLUSION: Patients with non-insulin-treated T2D who test BG daily
      may be those struggling for control. For others, benefits seem minimal for the
      proportion utilising self-monitoring.

PMID- 24024227
TI  - Skin surface temperature: a possible new outcome measure for skin and soft tissue
      infection.
AB  - BACKGROUND: This study describes the novel use of skin surface temperature to
      measure the severity and the response to treatment of skin and soft tissue
      infection (SSTI). METHODS: Patients admitted with SSTI for intravenous antibiotic
      therapy. Skin temperature was measured daily at the point of maximum heat on the
      SSTI affected limb and the non-affected limb using a non-contact laser
      thermometer. FINDINGS: Sixty-three patients were included. Mean length of stay
      was 4.95 days. The difference between affected and unaffected limb was 3.5
      degrees  C (95% CI 3.0-3.9) at day one and 2.1 degrees  C (95% CI 1.7-2.6) on the
      last day, a difference of 1.4 degrees  C (95% CI 0.7-1.9). Between day one and
      the last day, there was a significant reduction in affected limb temperature
      (mean reduction of 2.4 degrees  C, 95% CI 1.9-3.0 p<0.001). INTERPRETATION: Skin
      surface temperature may hold a useful role in the management of SSTI.

PMID- 24024228
TI  - Persistence on warfarin in patients with atrial fibrillation: experience in
      Australia 2006-2009.
AB  - BACKGROUND: Long-term persistence on warfarin in patients with non-valvular
      atrial fibrillation is essential to minimise thromboembolic complications,
      especially ischaemic stroke. This study examines persistence in Australian
      patients with presumed atrial fibrillation newly prescribed warfarin. METHODS:
      Longitudinal assessment of Pharmaceutical Benefit Scheme payment claim records
      from October 2006 through September 2009 in a 10% random sample of the Australian
      population holding long-term concession cards. MAIN OUTCOME MEASURES: proportion
      not filling first repeat prescription, median persistence time on medication,
      long-term persistence at 33 months. RESULTS: A total of 1 108 patients
      (representative of 11 080 nationally) were newly prescribed warfarin; mean age 74
      years, 50% were females. Fifteen percent (95% CI: 13-17) failed to collect the
      first repeat prescription, median persistence time on medication was only 12
      months (95% CI: 10-13), long-term persistence at 33 months was 26% (95% CI: 23
      27). DISCUSSION: There is significant discontinuation of warfarin therapy. When
      due to non-compliance, an opportunity for stroke prevention is being lost.

PMID- 24024229
TI  - A is for aphorism--'medicine is my lawful wife, and literature is my mistress.
      When I get [fed up with] one, I spend the night with the other.'.
AB  - 'I feel more confident and more satisfied with myself when I reflect that I have
      two professions and not one. Medicine is my lawful wife, and literature is my
      mistress. When I get tired of one I spend the night with the other. Though it is
      irregular, it is less boring this way, and besides, neither of them loses
      anything through my infidelity.' 

PMID- 24024230
TI  - Managing professional boundaries.
AB  - The maintenance of boundaries in the doctor-patient relationship is central to
      good medical practice and the appropriate care of patients. This article examines
      the nature of boundaries in medical practice and outlines some strategies to
      minimise the risk of a boundary violation.

PMID- 24024231
TI  - Light-emitting diode based shifted-excitation Raman difference spectroscopy (LED
      SERDS).
AB  - Fluorescence interference is a common problem in Raman spectroscopy. A low-cost
      solution using shifted-excitation Raman difference spectroscopy (SERDS) with a
      light-emitting diode (LED) is presented. A conventional dielectric bandpass
      filter is employed to narrow the spectral bandwidth of the LED radiation and to
      stabilize its wavelength. Moreover, angle-tuning of the filter allows the
      wavelength to be controlled and shifted in order to record SERDS spectra. 

PMID- 24024232
TI  - Demand-supply of neurointerventionalists for endovascular ischemic stroke
      therapy.

PMID- 24024233
TI  - Varicella-zoster virus encephalitis and vasculopathy in a patient  treated with
      fingolimod.

PMID- 24024234
TI  - Withholding CPR: a matter of policy?

PMID- 24024235
TI  - Withholding CPR: a matter of policy?

PMID- 24024236
TI  - 150 years of Friedreich ataxia: from its discovery to therapy.

PMID- 24024237
TI  - Reply to Rice and Henderson-Sellers: Survival of the fittest is not always the
      best option.

PMID- 24024238
TI  - Reply to Kennedy et al.: Katrina storm records in tide gauges.

PMID- 24024239
TI  - The authors reply.

PMID- 24024240
TI  - The authors reply.

PMID- 24024241
TI  - Three-dimensional modeling and simulation of DNA hybridization kinetics and mass
      transport as functions of temperature in a microfluidic channel.
AB  - A 3D finite element model was developed to optimize the kinetics and mass
      transfer characteristics of low concentration, 18 bp ssDNA targets in bulk media
      solution, to 18 bp complimentary oligonucleotide probes immobilized on
      electrochemical detection electrodes positioned along the length of a
      microfluidic channel. Conditions considered in the model were fluid flow rate,
      diffusion time, DNA melting temperature, number of matching base pairs, and
      temperature of the fluid in the channel. System optimization was based on
      maximizing the uniformity and surface concentration of the specifically bound
      hybridized DNA, minimizing waste volume generation and the hybridization time.
      With the coupled simulation method used, the total experiment time was reduced
      from 150 to 60 min and the simulated results were consistent with experimental
      results found in the literature. A stopped flow procedure was investigated as a
      means to improve hybridization. This procedure can not only improve uniformity
      and capture efficiency, and reduce waste, but can also decrease overall signal
      intensity relative to continuous flow operation. Finally, the use of temperature
      in reducing mismatched hybridization and improving duplex stability was also
      successfully modeled and simulated.

PMID- 24024242
TI  - Microfluidic tool coupled with electrochemical assay for detection of lactoferrin
      isolated by antibody-modified paramagnetic beads.
AB  - Lactoferrin (LF) is approximately 80 kDa iron-binding protein, which is important
      part of saliva and other body fluids. Due to its ability to bind metal ions, it
      has many biologically important functions. In this study, a method for the
      isolation of LF from a biological sample using robotically prepared antibody
      modified paramagnetic particles was developed using robotic pipetting station.
      The method consisted of the following optimised steps. Protein G was bound on the
      paramagnetic particles, on which goat antibody (10 MUg) was linked. LF was
      subsequently added to microtitration plate, which had affinity to goat antibody
      and the interaction lasted for 30 min. We found that the highest signals were
      obtained using the combination of goat antibody 1:3000, murine antibody 1:5000
      and conjugate 1:1500. Horseradish peroxidase reducing 3,3,5,5
      tetramethylbenzidine (TMB) was linked to the merged complex. The resulted product
      of this reaction was subsequently analysed spectrometrically with detection limit
      (3 S/N) as 5 ng/mL. In addition, we also determined TMB by stopped flow injection
      analysis with electrochemical detection. The limit of detection (3 S/N) was
      estimated as 0.1 MUg/mL. To compare spectrometric and electrochemical approach
      for detection of TMB, calibration range of bead-LF-antibodies complex was
      prepared and was determined using a least-squares correlation with coefficient R2
      higher than 0.95, indicating a very good agreement of the results obtained.

PMID- 24024243
TI  - Microchannel plate as a novel bipolar electrode for high-performance enrichment
      of anions.
AB  - Microchannel plate (MCP), a high-porosity glass membrane used as an electron
      multiplier in analytical/scientific instruments for the detection of energetic
      photons and charged particles is demonstrated here as a highly effective bipolar
      electrode (BPE) for electrokinetic focusing of anions. Assembled between a pair
      of microfluidic channels filled with an electrolyte buffer and subjected to a
      sufficient bias potential, MCP supports faradaic reactions, owing to its
      semiconducting characteristics. Thousands of microcapillary tubes fused together
      define MCP and act in unison such that each microcapillary serves as a tiny BPE
      surrounding an infinitesimal element of bulk electrolyte with a large surface
      area-to-volume ratio and hence performs highly effective as compared to a planar
      electrode inlaid into a microchannel. This performance has been validated here
      where concentration enrichment of a fluorescent tracer has been demonstrated at a
      remarkable rate of up to 175-fold/s exceeding those reported for planar BPEs. We
      attribute such high performance to the rapid onset of ion-depletion zone and
      subsequent steep field gradient, signifying the high-porosity structure of MCP as
      an effective BPE.

PMID- 24024244
TI  - ["We ask you to be a little patient!"].

PMID- 24024245
TI  - [Disaster management: challenges on many fronts].

PMID- 24024246
TI  - [Author's reply].

PMID- 24024247
TI  - Autologous mesenchymal stem cells for treating knee osteoarthritis.

PMID- 24024248
TI  - Breakthrough drug category demands more communication.

PMID- 24024249
TI  - Twilight for fee for service?

PMID- 24024250
TI  - Health care reform injects economics into the biologics 'value equation'.

PMID- 24024251
TI  - Noncancer research quietly advances this summer.

PMID- 24024252
TI  - Doctors see consolidation in their future.

PMID- 24024253
TI  - Acute kidney injury:  more common than you may think.

PMID- 24024254
TI  - Facing the challenges of aphasia.

PMID- 24024255
TI  - Protecting aging skin from these common disorders.

PMID- 24024256
TI  - Recognizing the subtle signs of ovarian cancer.

PMID- 24024257
TI  - Are canned fruits and vegetables a healthy alternative to fresh produce?

PMID- 24024258
TI  - Should I use heat or ice to ease knee pain from osteoarthritis?

PMID- 24024259
TI  - Sleep sedative warning.

PMID- 24024260
TI  - Computing radiation risks from CT scans.

PMID- 24024261
TI  - Revised diabetes guidelines.

PMID- 24024262
TI  - Limiting endoscopies for GERD patients.

PMID- 24024263
TI  - [IgA nephropathy and tonsillectomy].

PMID- 24024264
TI  - [Current topics of tongue and oral cancer-swallowing ability after surgery].

PMID- 24024265
TI  - [Social welfare supporting by daily practice].

PMID- 24024266
TI  - [Development of nanoparticle for coagulant].

PMID- 24024267
TI  - [Risk management of otolaryngology at the clinics].

PMID- 24024268
TI  - [Ultrasonography under otolaryngology and head and neck surgery].

PMID- 24024269
TI  - [Diagnosis and treatment of refractory pharynx ulcer].

PMID- 24024270
TI  - [Clinical pathology and treatment of undifferentiated thyroid cancer].

PMID- 24024271
TI  - [MTX associated lymphoproliferative disorder].

PMID- 24024272
TI  - [Current topics and future to vaccine for pancreatic cancer].

PMID- 24024273
TI  - Identifying barriers to receiving preventive dental services: expanding access to
      preventive dental hygiene services through affiliated practice.
AB  - PURPOSE: Minority children and children from lower income families are more
      likely to experience the burden of oral disease. Since oral disease reduces
      quality of life, it is a priority to utilize preventive dental services. The
      research questions ask if affiliated practice increases utilization of preventive
      dental services by underserved children from birth to 18 years of age, and what
      the barriers to receiving preventive dental services are and their level of
      importance. METHODS: A survey was administered to parents/guardians of patients
      from birth to 18 years of age who received preventive dental services from
      Catholic Healthcare West East Valley Children's Dental Clinic, an affiliated
      practice dental clinic in Chandler, Arizona. Thirty-four surveys were completed:
      21 completed in English and 13 completed in Spanish. The data was analyzed to
      provide descriptive statistics and non-parametrically analyzed using the
      Friedman's, Kendall's W and Wilcoxon Signed Ranks Tests. RESULTS: The cost of
      preventive dental services is more important to this population than both
      convenience of appointment time and distance traveled. As the cost increases for
      preventive dental services, this population will utilize preventive dental
      services less frequently. CONCLUSION: The study indicated that the increase of
      self-reported utilization of preventive dental services by underserved children,
      ranging in age from birth to 18 years old, in Arizona affiliated practice dental
      clinics, was primarily impacted by perceived reduced costs of receiving care.
      Funding efforts, reimbursement mechanisms and legislative policies should support
      this dental care delivery model to provide care to underserved children, adults
      and seniors throughout the U.S.

PMID- 24024274
TI  - [Current topics of invasiveness mycosis of paranasal sinuses].

PMID- 24024276
TI  - [Stabilograph based on body equilibrium].

PMID- 24024277
TI  - [Plastic surgery to head and neck area].

PMID- 24024275
TI  - [Current topics of team care for tongue and oral cancer].

PMID- 24024278
TI  - [Diagnosis and treatment of pharynx necrosis].

PMID- 24024279
TI  - [Tonsillectomy in IgA nephropathy patients].

PMID- 24024280
TI  - [Recommendations for prescribing combined hormonal contraceptives].

PMID- 24024281
TI  - Don't sit--get fit!

PMID- 24024282
TI  - Soring, antimicrobials, and layer hens.

PMID- 24024283
TI  - Compounding policies updated in anticipation of federal action.

PMID- 24024284
TI  - Veterinary technician, other accreditation policies modified.

PMID- 24024285
TI  - Disaster preparedness sessions funded by AVMF.

PMID- 24024286
TI  - East meets West, again.

PMID- 24024287
TI  - An educational philanthropist.

PMID- 24024288
TI  - Aid for those most in need.

PMID- 24024289
TI  - Happy birthday, JCDA.

PMID- 24024290
TI  - Digital radiography during implant osteotomy.

PMID- 24024291
TI  - Writing about the other guy.

PMID- 24024292
TI  - Dental ethics: professional challenges in a changing world.

PMID- 24024293
TI  - Would someone please explain what it means to be ethical?
AB  - Definitions are offered to distinguish among behavior that is legal, charitable,
      professional and moral. Moral acts are especially important because that is what
      people do to bring about the right and the good that is mutually sought by
      dentists, patients and the community. Ethics is an academic discipline that
      teaches about appropriate behavior in an indirect fashion - what we say to
      justify what we do.

PMID- 24024294
TI  - The ethics of social media in dental practice: challenges.
AB  - This is the first of two essays written to consider several important trends in
      dental practice that result from innovations in digital and social media. This
      essay reviews ethical and legal implications of the use of websites, Facebook,
      review sites, email and other digital innovations in dental practice. The second
      essay provides ethical tools for analysis, illuminates areas of ethical concern
      in today's practice environment and offers recommendations for future practice.

PMID- 24024295
TI  - The ethics of social media in dental practice: ethical tools and professional
      responses.
AB  - This article considers several important trends in dental practice that result
      from innovations in digital and social media. It provides ethical tools for
      analysis, Illuminates areas of ethical concern in the current practice
      environment and offers recommendations for future practice. A summary in the form
      of a checklist is posted at the end of this essay for dentists considering the
      use of social media in their practice.

PMID- 24024296
TI  - Care versus commerce: a challenge to professional integrity?

PMID- 24024297
TI  - Our next generation: dental student ethics and its potential influence on the
      profession.

PMID- 24024298
TI  - CDA Judicial Council: blending idealism and practicality.
AB  - The California Dental Association Judicial Council has the responsibility for
      interpreting and enforcing the Code of Ethics, for disciplining members and for
      fostering a climate of education and ethics awareness for CDA members. The
      Council recognizes the inherent difficulty in rigid enforcement of the Code of
      Ethics, and chooses to take an approach that educates and encourages members to
      embrace the highest standards of our profession as outlined in the Code.

PMID- 24024299
TI  - Road signs on the road of life. Student professional and ethics presentation,
      University of the Pacific, Arthur A Dugoni School of dentistry in San Francisco.

PMID- 24024300
TI  - The beginning.

PMID- 24024301
TI  - A sensitive shock index for real-time patient assessment during simulated
      hemorrhage.
AB  - BACKGROUND: Shock index [SI = the ratio of heart rate (HR) to systolic arterial
      pressure (SAP)] is a metric used to diagnose patients at risk of impending
      hemorrhagic shock. We hypothesized that a metric called the compensatory reserve
      index (CRI), derived using computer modeling with continuous feature extraction
      from arterial waveforms, would provide an earlier indicator of cardiovascular
      instability than SI during progressive central hypovolemia. METHODS: There were
      15 subjects (men = 8; women = 7) who underwent progressive reduction in central
      blood volume induced by lower body negative pressure (LBNP) until SAP < 90 mmHg.
      CRI was normalized on a scale of 1 (normovolemia) to 0 (circulatory volume at
      which instability occurs) and displayed on a colored bar. The times at which the
      CRI equaled 0.6 (threshold of green to amber) or 0.3 (threshold of amber to red)
      were compared to a clinical threshold of SI > or = 0.9. RESULTS: A SI > or = 0.9
      required 22.4 +/- 6.2 min (95% CI = 19 to 25.8 min). CRI reached 0.6 (amber) at
      12.5 +/- 4.9 min (95% CI = 9.8 to 15.3 min) when SI = 0.61 +/- 0.03, and became
      0.3 (red) at 20.3 +/- 5.1 min (95% CI = 17.5 to 23.1 min) when SI = 0.81 +/- 1.4.
      CONCLUSIONS: CRI provided a significantly earlier indicator of impending
      hemodynamic decompensation than SI > or = 0.9 during progressive LBNP. These
      results support the notion that the CRI represents an improved 'shock index' as
      an indicator of impending hemorrhagic shock compared to standard vital signs.

PMID- 24024302
TI  - Heat shock stress prior to hyperbaric oxygen exposure in rats.
AB  - INTRODUCTION: Heat shock proteins (HSPs) and nuclear factor-kappa B (NF-kappaB)
      have been established as important mediators in lung injury; however, their role
      in preventing pulmonary toxicity from hyperbaric oxygen (HBO) has not been
      evaluated. METHODS: We aimed to study the effects of heat shock (HS) injury on
      hyperbaric hyperoxic lung injury (HHLI) in a rat model and identify a mechanism
      of protection by evaluating HSP 27 and HSP 70 mRNA and protein levels, NF-kappaB
      p65, lung injury and oxidative parameters. By varying the times between HS and
      exposure to HBO, the pathways of interaction between HSPs and NF-kappaB will be
      further clarified. RESULTS: Our results showed that HS exposure increases the
      mRNA and protein levels of HSP 27 and HSP 70; HS induced 10-fold increases of HSP
      27 (9.77 +/- 0.60) and HSP 70 (10.33 +/- 2.4) within the first 10 h compared to
      control animals. Lesion scores were higher for the first 16 h after HS, but
      decreased again after 31 h (N = 7 animals; 5 lesions scores). Protein nitration
      showed no significant differences between groups exposed to HS or HBO; similarly
      there was no difference with a combination of both treatments. DISCUSSION: HBO
      appears to attenuate the HS response by HSP 27 and HSP 70. Histopathology results
      suggest that HS might mitigate pathology in animals exposed to HS and HBO. No
      significant effect of HS on HBO-induced HHLI was observed in animals treated with
      both HS and HBO.

PMID- 24024303
TI  - Cognitive function during lower body water immersion and post-immersion
      afterdrop.
AB  - INTRODUCTION: The physiological effects of immersion hypothermia and afterdrop
      are well-characterized, but the psychological effects are less clear. The purpose
      of this study was to quantify changes in cognitive function during and after
      lower body water immersion. METHODS: On separate mornings, nine young healthy men
      participated in both neutral (35 +/- 1 degree C) and cold (13 +/- 1 degree C)
      water immersion. Subjects rested in neutral air for 30 min followed by 60 min
      water immersion to the iliac crest and 15 min of recovery in neutral air. Rectal
      temperature and mean skin temperature were continuously monitored. Metabolic
      rate, the Stroop Color Word Test (SCWT), and the Profile of Mood State (POMS)
      were quantified at predetermined intervals. RESULTS: During immersion in cold
      water, rectal temperature was reduced, but SCWT and POMS scores were unchanged
      relative to baseline. Despite the reduced rectal temperature, little to no
      shivering was observed during immersion and metabolic rate did not change. During
      recovery from cold immersion, rectal temperature was further reduced by
      approximately 0.5 degree C, shivering was noted, and metabolic rate increased.
      Coincident with this acute afterdrop, SCWT Color-Word performance (delta = -4 +/-
      8 vs. 7 +/- 6 correct responses) and Interference score (delta = -2 +/- 7 vs. 4
      +/- 8) was impaired relative to recovery from neutral immersion (i.e., when core
      temperature and metabolic rate did not change). CONCLUSION: These results suggest
      that recovery from lower body cold water immersion elicits the afterdrop
      phenomenon and shivering, which together impair selective attention as measured
      by the SCWT.

PMID- 24024304
TI  - Predicting individual differences in response to sleep loss: application of
      current techniques.
AB  - BACKGROUND: Fatigue's negative impact on safety represents one of the top threats
      to military transportation. Biomathematical models have been developed to predict
      the response to fatigue; however, current models do not take into account stable
      individual differences in fatigue susceptibility. Readiness Screening Tools
      (RSTs) can capture individual differences in fatigue response, but cannot predict
      performance long-term. The objective of this study was to combine an existing
      biomathematical model of fatigue with existing RST-derived measures to determine
      current ability to predict individual differences in fatigue response. We
      hypothesized that the predictive ability of the biomathematical model could be
      significantly improved by incorporating cognitive and oculometric measures shown
      to be sensitive to individual differences in fatigue response. METHODS: Data on
      multiple cognitive and oculometric measures were collected at rested baseline and
      then every 3 h across 25 h of continual wakefulness. Results characterized actual
      fatigued performance at the group and individual levels. Actual performance was
      compared to predicted performance decrements over the same time period. The
      unique variance explained by each approach was then combined to determine if RST
      derived individual difference measures added significant predictive power to the
      model. RESULTS: Addition of individual-difference sensitive RST measures to an
      existing fatigue model significantly increased the amount of variance in
      performance explained by the model from 13.8 to 35.7%. DISCUSSION: Simply
      leveraging RSTs' ability to capture individual differences in fatigue
      susceptibility can substantially improve biomathematical prediction of fatigued
      performance.

PMID- 24024305
TI  - Simulation of gas bubble growth and dissolution in human tissues during dives and
      recompression.
AB  - BACKGROUND: As is known, there are many cases when symptoms of decompression
      sickness (DCS) in divers appear extremely late (> 15 h after completion of
      diving) and there is much evidence for unsuccessful treatment of DCS by means of
      recompression. In this study, we have tried to gain insight into the roots of
      these phenomena. METHODS: Using the mathematical model of extravascular gas
      bubble dynamics, we have analyzed the time history of such bubbles under typical
      air dives and recompression procedures used for DCS treatment. RESULTS: If the
      parameters defining the bubble dynamics remained invariable, the bubbles formed
      in different body tissues would reach their maximal sizes within the well-known
      latency time range for DCS onset, and later these bubbles would dissolve
      completely during standard recompression procedures. Actually, the parameters
      defining the processes of bubble growth and dissolution vary with time.
      CONCLUSIONS: The symptoms of DCS that arise with abnormal latency may be induced
      by bubbles that grow a very long time in some tissues when the rate of nitrogen
      washout from them is reduced significantly due to vascular bubbles blocking the
      microcirculation. An abnormal latency of DCS onset may also appear when the
      negative effects of the initially asymptomatic bubbles are detected during the
      very slow process of their dissolution. The failure of recompression to resolve
      this DCS probably happens when the previously formed bubbles are large and
      located in tissues with less permeability so that they dissolve very slowly.

PMID- 24024306
TI  - Intracranial pressure and optic nerve sheath diameter as cephalic venous pressure
      increases in swine.
AB  - BACKGROUND: Nontraumatic, nonhydrocephalic increases in intracranial pressure
      (ICP) are often difficult to diagnose and may underlie spaceflight-related visual
      changes. This study looked at the utility of a porcine animal model of increasing
      cephalic venous pressure to mimic acute changes in ICP and optic nerve sheath
      diameter (ONSD) from cephalic venous fluid shifts observed during spaceflight.
      METHODS: Anesthetized juvenile piglets were assigned to groups of either naive (N
      = 10) or elevated superior vena cava pressure (SVCP; N = 20). To elevate SVCP, a
      6F custom latex balloon catheter was inserted and inflated to achieve SVCP of 20
      and 40 mmHg for 1 h at each pressure. In both groups, serial measurements of ICP,
      internal jugular pressure (IJP), and external jugular pressure (EJP) were made
      hourly for 3 h, and ONSD of the right eye was measured hourly by ultrasound (US).
      RESULTS: There was a significant linear correlation between IJP and ICP (slope:
      0.9614 +/- 0.0038, r = 0.9683). With increasing SVCP, resulting ONSD was also
      well correlated with the ICP (slope: 0.0958 +/- 0.0061, r = 0.7841). The receiver
      operating characteristic curve for ONSD in diagnosing elevated ICP had an area
      under the curve of 0.9632 with a sensitivity and specificity of 92% and 91%,
      respectively, for a cutoff of 5.45 mm. CONCLUSIONS: Increases in SVCP result in
      ICP changes that are well correlated with alteration in ONSD. These changes are
      consistent with observed ONSD changes monitored during spaceflight.

PMID- 24024307
TI  - Pilot perception and confidence of location during a simulated helicopter
      navigation task.
AB  - INTRODUCTION: This paper aims to provide insights into human perception,
      navigation performance, and confidence in helicopter overland navigation.
      Helicopter overland navigation is a challenging mission area because it is a
      complex cognitive task, and failing to recognize when the aircraft is off-course
      can lead to operational failures and mishaps. METHODS: A human-in-the-loop
      experiment to investigate pilot perception during simulated overland navigation
      by analyzing actual navigation trajectory, pilots' perceived location, and
      corresponding confidence levels was designed. There were 15 military officers
      with prior overland navigation experience who completed 4 simulated low-level
      navigation routes, 2 of which entailed auto-navigation. This route was paused
      roughly every 30 s for the subject to mark their perceived location on the map
      and their confidence level using a customized program. RESULTS: Analysis shows
      that there is no correlation between perceived and actual location of the
      aircraft, nor between confidence level and actual location. There is, however,
      some evidence that there is a correlation (rho = -0.60 to approximately 0.65)
      between perceived location and intended route of flight, suggesting that there is
      a bias toward believing one is on the intended flight route. DISCUSSION: If
      aviation personnel can proactively identify the circumstances in which usual
      misperceptions occur in navigation, they may reduce mission failure and accident
      rate. Fleet squadrons and instructional commands can benefit from this study to
      improve operations that require low-level flight while also improving crew
      resource management.

PMID- 24024308
TI  - Flat spin and negative Gz in high-altitude free fall: pathophysiology,
      prevention, and treatment.
AB  - INTRODUCTION: Red Bull Stratos was a commercial program that brought a test
      parachutist protected by a full pressure suit to 127,852 ft (38,964 m), via a
      stratospheric balloon with a pressurized capsule, from which he free fell and
      subsequently parachuted to the ground. In light of the uniqueness of the
      operation and the medical threats faced, medical protocols specific to
      distinctive injury patterns were developed. One unique threat was that of a flat
      spin during free fall with resultant exposure to -Gz (toe-to-head) acceleration.
      In preparation for stratospheric free fall, the medical team conducted a review
      of the literature on the spectrum of human and animal injury patterns
      attributable to -Gz exposures. Based on the findings, an emergency medical field
      response protocol was developed for the rapid assessment, diagnosis, and
      treatment of individuals suspected of -Gz injury. METHODS: A systematic review
      was conducted on available literature on human and animal studies involving
      significant -Gz exposure, with subsequent development of an applicable field
      treatment protocol. RESULTS: The literature review identified pathophysiologic
      processes and mitigation strategies that were used to develop a prevention and
      treatment protocol, outlining appropriate interventions using current best
      medical practices. A medical field treatment protocol was successfully
      established for the high-altitude balloon program. DISCUSSION: Available
      literature provided insight into best medical practices for the prevention and
      treatment of significant -Gz exposures during high-altitude parachute activity.
      Using the protocol developed for the field medical response, injuries from
      sustained -Gz exposure can be effectively managed in similar high-altitude and
      space operations.

PMID- 24024309
TI  - Perceived gravitoinertial force during vection.
AB  - BACKGROUND: When we ride on a roller coaster, our experience of self-motion is
      accompanied by salient changes in gravitoinertial force. Here we examined whether
      a similar relationship exists between visually induced self-motion (vection) and
      perceived gravitoinertial force. METHODS: There were 15 stationary subjects, each
      wearing a weight jacket, who were exposed to visual displays simulating upward,
      backward, or no self-motion. At the end of each 30-s display exposure, subjects:
      1) rated the strength of their vection experience; and 2) had the experimenter
      add/remove weights from their weight jackets to recreate their perceived weight
      during exposure to the stimulus display. RESULTS: We found that upward vection
      increased and downward vection decreased perceived weight. Importantly, the size
      of these perceived weight changes depended on the strength of the vection
      experience. CONCLUSIONS: We conclude that the observed strong relationship
      between vection and perceived weight stems from the brain's attempt to reconcile
      the inputs from the different self-motion senses. The current findings have
      important implications for all simulated self-motions either in virtual reality
      or in vehicle simulators (particularly fixed-base flight and driving simulators).

PMID- 24024310
TI  - Sensorineural hearing loss incidence among U.S. military aviators between 1997
      and 2011.
AB  - INTRODUCTION: Noise-induced hearing loss is the most common cause of
      sensorineural hearing loss (SNHL) in military aviation. Few published studies
      compare SNHL rates between fixed and rotary-wing military pilots. The study's
      objective was to determine whether a difference in mean annual SNHL incidence
      rate exists between fixed and rotary wing aviators in the U.S. Army, Navy, Air
      Force, and Marines. METHODS: SNHL rates (new cases annually/1000 persons-per
      year) for U.S. military aviators from 1997-2011 were extracted from the Defense
      Medical Epidemiology Database (DMED). ANOVA was conducted for mean annual SNHL
      incidence rate differences and for interaction effects between aircraft type,
      fixed or rotary-wing, and service branch. RESULTS: A total of 467,064 person
      years were analyzed. A main effect existed for aircraft type, such that the mean
      annual rate of SNHL was higher for fixed (M = 15.8, SD = 10.2) than for rotary
      wing aviators (M = 8.7, SD = 5.0, RR = 1.8). Service branch main effect was
      significant, such that the mean SNHL rates were greater for the Army (M = 19.6,
      SD =11.2) and Air Force (M = 14.7, SD = 11.2) than for the Navy (M = 7.2, SD =
      3.9) and Marines (M = 7.3, SD = 3.6). The interaction effect was significant,
      indicating that the within branch differences in SNHL rate between fixed and
      rotary-wing aviators is greater in the Army and Air Force than in the Navy and
      Marines. DISCUSSION: The average annual incidence rate of SNHL between 1997-2011
      was higher for fixed than for rotary-wing aviators, and higher for U.S. Army and
      Air Force than Navy and Marine aviators. An examination of hearing conservation
      programs and engineering controls may be warranted.

PMID- 24024311
TI  - Neuropsychological assessment of decision making in alcohol-dependent commercial
      pilots.
AB  - BACKGROUND: The aim of this exploratory archival study was to discern the utility
      of the Iowa Gambling Task (IGT) in identifying adaptive decision-making
      capacities among pilots with a history of alcohol dependence both with and
      without Cluster B personality features. METHODS: Participants included 18 male
      airmen at the rank of captain with a history of receiving alcohol dependence
      treatment and subsequent referral for a fitness-for-duty evaluation. Data from
      prior comprehensive neuropsychological evaluations conducted in a private
      practice setting at the mandate of the FAA utilizing criteria outlined in the
      HIMS program was used. ANOVA was conducted to compare pilots with (N = 4) and
      without Cluster B personality features (N = 14) on measures of decisionmaking
      capacities, intelligence, and executive functioning. RESULTS: Pilots with Cluster
      B personality features were found to have a significantly lower Total Net T-Score
      on IGT (M = 35.00, SD = 9.27) than pilots without features of Cluster B (M =
      56.36, SD = 9.55). Furthermore, with the exception of the first 20 cards (i.e.,
      Net 1); the groups significantly differed in their Net scores. No statistically
      significant difference was found on airmen's intelligence and executive
      functioning. DISCUSSION: The present study found that alcohol-dependent airmen
      with Cluster B personality features evidenced significantly poorer decisionmaking
      capacities as measured by the ICT in comparison to alcohol dependent airman
      without Cluster B personality features. Implications and limitations of the study
      are discussed.

PMID- 24024312
TI  - Central retinal vein occlusion following hypobaric chamber exposure.
AB  - BACKGROUND: Mountain climbers who ascend to a high altitude could suffer high
      altitude retinopathy, which varies from tortuous retinal vessels and hemorrhages
      to retinal vascular obstruction. As hypobaric chamber training could imitate a
      fast ascent and could lead to decompression sickness, a simulated flight could
      also lead to a high altitude retinopathy. CASE REPORT: This paper will present a
      case of central retinal vein occlusion that occurred after exposure to a
      hypobaric chamber and Valsalva maneuver. Although the patient was treated with an
      intravitreal bevacizumab injection, his macular edema was aggravated after a
      helicopter flight, which involved re-exposure to high altitudes and a Valsalva
      maneuver. DISCUSSION: Systemic evaluation including blood coagulation and carotid
      Doppler studies did not reveal any lesion. Notably, central retinal vein
      occlusion can occur in young, healthy individuals after hypobaric chamber
      exposure.

PMID- 24024313
TI  - In-flight incapacitation and cystic medial necrosis.
AB  - INTRODUCTION: The major causes of in-flight fatal incapacitation in civil pilots
      are acute coronary events, new onset idiopathic epilepsy, and physiological
      problems. Less than 1% of all air accidents are due to sudden incapacitaion. The
      problem with acute coronary disease is very serious when occurring during
      critical stages of the flight, such as takeoff or landing, rather than during the
      cruising phase. CASE REPORT: The authors describe the fatal in-flight
      incapacitation in a Czech airline captain during the approach for landing. In
      this case, the first officer tried to communicate with the captain, but there was
      no response and first aid was unsuccessful. The post-mortem examination showed
      the cause of the sudden death to be an aortic dissection with cardiac tamponade
      due to cystic medial necrosis (Erdheim disease). The authors describe the
      clinical and histological features of Erdheim disease. DISCUSSION: The normal
      aorta contains collagen, elastin, and smooth muscle cells that form the vessel
      wall. Degenerative changes lead to breakdown of the collagen, elastin, and smooth
      muscle, and an increase in basophillic ground substance with the formation of
      cysts and accumulation of mucopolysaccharide. Medical incapacitation in the
      cockpit is rare. The leading causes of fatal in-flight incapacitation are
      myocardial infarction, cardiac arrhythmias, and epileptic seizures; cystic medial
      necrosis is very rare and no similar cases were found in the aviation literature.

PMID- 24024314
TI  - Anterior-posterior transcranial ultrasound to measure cranial oscillations.
AB  - BACKGROUND: We aimed to provide information on whether or not the correlation
      between body tilt and the pulse amplitude of transcranial ultrasonic time-of
      flight waveform can be observed in the anterior-posterior skull direction. Also,
      we asked the question whether or not the skull pulsation can be detected since
      the cranial bones involved are thicker. METHODS: The experimental model of body
      tilt that alters intracranial pressure by shifting body fluid headward was
      employed. Transcranial ultrasound waveforms were examined in 15 healthy
      volunteers positioned at five tilt angles of +30 degrees, 0 degrees, -30 degrees,
      -60 degrees, and -90 degrees from the horizontal body position. A pulse-echo
      transducer was placed on the middle forehead and ultrasound waveforms were
      recorded. Synchronized variations in the ultrasonic time-of-flight with
      heartbeats were monitored using the pulsed phase locked loop technique for the
      output voltage of the ultrasound transducer. Simultaneous effects of body tilt on
      cardiovascular parameters were also evaluated. RESULTS: Pulse amplitudes of
      ultrasonic time-of-flight waveforms were found to vary with body tilt. Repeated
      measures ANOVA and regression analysis showed a negative correlation between body
      tilt angle and pulse amplitude. The regression line has the equation: pulse
      amplitude = (1.158-0.01023 x tilt angle) x 10(-4) voltage. There was no such
      relationship between head-down body tilt and altered mean blood pressure or heart
      rate. CONCLUSION: An increase in the pulse amplitude of the anterior-posterior
      transcranial ultrasonic time-of-flight waveform can be detected when the head
      down body tilt angle increases.

PMID- 24024315
TI  - Front line manager's quick reference guide for organizational impact analysis.
AB  - In reference to the original research questions, there is organizational
      documented support for the QRG. FLMs perceived the QRG to have both effectiveness
      and utility. Both less experienced FLMs and more experienced FLMs found the QRG
      to be helpful, as indicated by intended use, with more experienced FLMs
      indicating a higher intended use. The ATO Office Safety Programs Fatigue Risk
      Management Group has requested an expansion of the QRG, including fatigue-related
      issues. Overall, the QRG has proven to be a useful and convenient document for
      all FLMs. As it becomes a recognizable and essential resource in both the
      training and management tool box, the use of the QRG will likely grow.

PMID- 24024316
TI  - You're the flight surgeon: high-altitude pulmonary edema.

PMID- 24024317
TI  - You're the flight surgeon: acute pancreatitis.

PMID- 24024318
TI  - Seventy-five years ago in September 1938.

PMID- 24024319
TI  - Role of dongchongxiacao (Cordyceps) in prevention of contrast-induced nephropathy
      in patients with stable angina pectoris.
AB  - OBJECTIVE: To study the preventative effects of Dongchongxiacao (Cordyceps) on
      contrast-induced nephropathy (CIN) in patients with stable angina pectoris (SAP).
      METHODS: One-hundred and three SAP inpatients were divided randomly into two
      groups: basic treatment (n = 51) and Dongchongxiacao (Cordyceps) treatment (n =
      52); corbrin capsules (3 g; t.d.s.) were used 3 days before angioplasty and 3
      days after angioplasty). Serum creatinine (Scr) was assessed at the time of
      hospital admission and 1, 2, and 3 days after angioplasty. Values of kidney
      injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and
      interleukin (IL) 18 in the kidney were detected before angioplasty and 1 day
      after angioplasty in the patients of both groups. The prevalence of CIN between
      the two groups was then compared. RESULTS: CIN occurred in 9 of 103 patients
      (8.74%). The prevalence of CIN in the Dongchongxiacao (Cordyceps) treatment group
      was lower than that of the basic treatment group (5.77% vs 11.76%) but the
      difference was not significant (P > 0.05). The post-procedure mean peak of Scr,
      post-procedure increase in Scr levels from baseline, and urine levels of KIM-1,
      NGAL and IL18 after the procedure in the Dongchongxiacao (Cordyceps) treatment
      group were significantly lower than those in the basic treatment group (P <
      0.05). CONCLUSION: Prophylactic treatment with Dongchongxiacao (Cordyceps) in SAP
      patients who undergo coronary angiography or coronary intervention could prevent
      contrast-induced renal impairment.

PMID- 24024320
TI  - Effects of electroacupuncture and Chinese kidney-nourishing medicine on
      polycystic ovary syndrome in obese patients.
AB  - OBJECTIVE: To explore the effect of electroacupuncture and Chinese kidney
      nourishing medicine on insulin (INS), adiponectin (APN), leptin (LEP), and
      glucolipid metabolism of obese patients with polycystic ovary syndrome (PCOS).
      METHODS: Sixty-seven obese PCOS patients were randomly divided into two groups.
      Thirty-three patients in the acupuncture-medicine group were treated three times
      a week with electroacupuncture at the Tianshu (ST 25), Zhongwan (CV 12), Qi-hai
      (CV 6), Sanyinjiao (SP 6), Geshu (BL 17), and Ciliao (BL 32) acupoints. They also
      took the Chinese drug, Tiankui capsule, for 3 months as a course of treatment.
      Point-taking and treatment in the electroacupuncture group of 34 patients was the
      same as those in the acupuncture-medicine group. We observed and compared the
      changes in the obesity-related indexes of body weight (BW), body mass index
      (BMI), and waist-hip ratio (WHR), as well as fasting plasma glucose (FPG),
      fasting insulin (FINS), APN, and LEP. RESULTS: BW, BMI, WHR, and FINS decreased
      and insulin sensitivity index (ISI) and APN were higher in the acupuncture
      medicine group than in the electroacupuncture group (P < 0.01). There was no
      obvious difference in LEP between the two groups (P > 0.05). CONCLUSION:
      Acupuncture combined with medicine is better than just electroacupuncture for
      obese PCOS patients by improving obesity-related indexes, insulin sensitivity,
      and APN level. This indicates that acupuncture-medicine therapy is worth clinical
      popularization.

PMID- 24024321
TI  - Analgesic effect of acupuncture at hegu (LI 4) on transvaginal oocyte retrieval
      with ultrasonography.
AB  - OBJECTIVE: To observe the analgesic effect of acupuncture at Hegu (LI 4) in vitro
      fertilization-embryo transfer (IVF-ET) transvaginal oocyte retrieval using
      ultrasonography and explore its mechanism. METHODS: Ninety patients undergoing
      IVF-EF oocyte retrieval were randomly divided into three groups: an acupuncture
      group with needles inserted into bilateral Hegu (LI 4) points, a placebo group
      given placebo needles, and a control group with routine oocyte retrieval. Each
      group had an indometacin enema 30 min before the operation. We compared the pain
      rated index (PRI), visual analogy scale (VAS), and present pain intensity (PPI)
      immediately after operation and 1 h after operation. We also determined the
      neuropeptide Y (NPY) level of the follicular fluid. RESULTS: PRI, VAS, and PPI
      after operation and 1 h after operation in the acupuncture group were
      significantly lower than those in the control group (P < 0.01). No obvious
      difference (P > 0.05) was observed in PRI, VAS, and PPI after operation and 1 h
      after operation between the placebo group and the control group. The NPY level of
      the follicular fluid in the acupuncture group was significantly higher than that
      in the control group (P < 0.01). No obvious difference (P > 0.05) was observed in
      the NPY level of the follicular fluid between the placebo group and the control
      group. CONCLUSION: The analgesic effect of acupuncture at Hegu in transvaginal
      oocyte retrieval using ultrasonography may be related to the increase in the NPY
      level of the follicular fluid.

PMID- 24024322
TI  - Effect of herbal formula xiao pi-II on functional dyspepsia.
AB  - OBJECTIVE: To investigate the therapeutic effect of the herbal medication Xiao Pi
      II on the symptoms and gastric motility of patients with functional dysepsia
      (FD). METHODS: A total of 180 FD patients were divided randomly and equally into
      Xiao Pi-II and mosapride groups. The two groups were treated with Xiao Pi-II (100
      mL, t.d.s., ante cibum) and mosapride (5 mg, t. d.s., ante cibum) for 2 weeks.
      Before treatment and 3 days after all medication was stopped, patients responded
      to a questionnaire evaluating gastrointestinal symptoms and were assessed with
      abdominal three dimensional ultrasonography (3D-US) for gastric motility.
      RESULTS: Gastrointestinal symptoms (especially bloating, post-prandial fullness
      and eructation) were improved significantly in FD patients treated with Xiao Pi
      II (P < 0.05, P < 0.05, and P < 0.05), but no significant difference was found in
      the mosapride group (P > 0.05). The effective rates in the Xiao Pi-II and
      mosapride group were 86.7% and 60.0%, respectively (P < 0.05). The gastric liquid
      emptying rate (GLER) in the Xiao Pi-II group showed a significant increase (P <
      0.01) after 2 weeks of treatment but there was no significant change (P > 0.05)
      of GLER in the mosapride group. CONCLUSION: Compared with mosapride, Xiao Pi-II
      improved symptoms and GLER significantly in FD patients with delayed gastric
      emptying.

PMID- 24024323
TI  - Influence of erbanxiao solution on inhibiting angiogenesis in stasis toxin
      stagnation of non-small cell lung cancer.
AB  - OBJECTIVE: To investigate the effects and mechanisms of Erbanxiao solution in
      inhibiting tumor angiogenesis. METHODS: We observed the effects and mechanisms of
      Chinese medicines on inhibiting tumor angiogenesis and studied the theories and
      results of treatment. Sixty patients with lung cancer were randomized into two
      groups (n = 30). Patients in the control group were given compound Kushen
      injection, and patients in the treatment group were given Erbanxiao solution. The
      effect of Erbanxiao solution on vascular endothelium growth factor (VEGF), basic
      fibroblast growth factor (bFGF), and tumor necrosis factor-alpha (TNF-alpha) was
      observed. RESULTS: The effective rate of the treatment group was 60% while the
      control group was 36%. There was a significant difference between the two groups
      (P < 0.05). VEGF, bFGF, and TNF-alpha levels of the two groups were significantly
      different before and after treatment (P < 0.01). These Traditional Chinese
      Medicines significantly inhibited tumor angiogenesis, possibly by changing levels
      of VEGF, bFGF, and TNF-alpha. CONCLUSION: It is necessary to further explore the
      potential of Traditional Chinese Medicine in the treatment of angiogenesis in
      tumor patients.

PMID- 24024324
TI  - Mechanism research on combination of decoction for reinforcing lung qi and argon
      helium lancet in treatment of non-small cell lung cancer.
AB  - OBJECTIVE: To observe the effect of decoction for reinforcing lung Qi on T
      lymphocytic function, interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF
      alpha) in peripheral blood of patients with non-small cell lung cancer after
      operation with argon helium lancet in order to explore its mechanism. METHODS: A
      total of 76 patients suffering from non-small cell lung cancer without surgical
      indication were randomly divided into a treatment group treated with decoction
      for reinforcing lung Qi and argon helium lancet and a control group treated with
      argon helium lancet only to observe lymphocytic proliferation, detect the
      percentage of positive cells in the T-lymphocyte CD28 with flow cytometry and
      detect the expression of IL-2 and TNF-alpha in peripheral blood with enzyme
      linked immunosorbent assay. RESULTS: Proliferation of T-lymphocytes and
      expression of CD28, IL-2 and TNF-alpha in peripheral blood after treatment in the
      treatment group were more obviously strengthened than those before treatment and
      those in the control group (all P < 0.05). CONCLUSION: The mechanism of using
      decoction for reinforcing lung Qi and argon helium lancet to treat lung cancer
      may be realized through promoting T-lymphocytic proliferation, up-regulating
      expression of CD28, IL-2 and TNF-alpha, and activating T-cells.

PMID- 24024325
TI  - Cancer incidence varies significantly depending on sasang constitution of
      traditional Korean medicine.
AB  - OBJECTIVE: Sasang constitutional medicine is a component of Traditional Korean
      Medicine that stresses the hereditary makeup of disease incidences or therapeutic
      responses. This study investigated the relationship between the incidence of
      cancer and Sasang constitution classification. METHODS: Five hundred and one
      cancer patients were classified as having one of the four types of Sasang
      constitutions (Taeumin, Soumin, Soyangin, Taeyangin) using Questionnaire for
      Sasang Constitution Classification II, then compared with data from 1423 healthy
      subjects. RESULTS: The Sasang constitutional distribution for the cancer patients
      was significantly different from that for healthy subjects: 22.8% vs 46.9% for
      Taeumin, 35.5% vs 24.0% for Soumin, and 41.7% vs 29.1% for Soyangin. Our results
      assumed that the lowest cancer incidence would be in Taeumin (around 2-fold in
      both sex) while the highest cancer incidence in Soumin males (2.8-fold) and
      Soyangin females (2.1-fold). CONCLUSION: This study identified a trend involving
      the frequency of cancer and the Sasang constitutional classification. We hope
      that this finding will provide new ideas for the study of cancer incidence and
      its preventive management.

PMID- 24024326
TI  - Factors associated with fatigue in acquired immunodeficiency syndrome patients
      with antiretroviral drug adverse reactions: a retrospective study.
AB  - OBJECTIVE: To retrospectively study the prevalence of fatigue and factors
      associated with fatigue among acquired immunodeficiency syndrome (AIDS) patients
      with antiretroviral drug adverse reactions. METHODS: Data were collected from
      case report forms (CRFs) for a project funded by the 11th National 5-year Special
      Science and Technology Program on Major Infectious Diseases. Fatigue was defined
      by patient self-report. The outcomes were the prevalence of fatigue and the
      potential risk factors of fatigue. Univariate and multivariate logistic
      regression analyses were conducted to identify the factors associated with
      fatigue. RESULTS: Among the 228 subjects, the prevalence of fatigue was 86.8%. In
      univariate analysis, the significant differences in demographic characteristics
      between patients with and without fatigue were: gender [OR = 2.29; 95% CI (1.05
      4.98)], education level [OR = 0.40; 95% CI (0.18-0.85)], anemia [OR = 3.80; 95%
      CI (1.27-11.31)], time of HIV diagnosis [OR = 0.29; 95% CI (0.13-0.65)], and
      route of infection [OR = 0.14; 95% CI (0.06-0.32)]. Abnormal taste and rapid
      pulse were more commonly seen in patients with fatigue (P < 0.05), while
      abdominal distension and lumbar soreness were encountered less often in patients
      with fatigue (P < 0.05). Multivariate analysis showed that the four main factors
      associated with fatigue were anemia [OR = 3.50; 95% CI (1.01-12.15)], route of
      infection [OR = 3.40; 95% CI (1.21-9.58); P = 0.02 < 0.05], lumbar soreness [OR =
      0.06; 95% CI (0.02-0.18); P = 0.000 < 0.05], and rapid pulse [OR = 10.58; 95% CI
      (2.16-51.75); P = 0.004 < 0.05]. CONCLUSION: This study demonstrated that fatigue
      is common (86.8% prevalence) in AIDS patients with antiretroviral drug adverse
      reactions, and that anemia, route of infection (i.e., non-commercial blood
      donation) and rapid pulse were risk factors, while lumbar soreness was a
      protective factor related to fatigue. More attention should be paid to fatigue
      and more efforts should be made to find ways to prevent, control and eliminate
      this symptom in AIDS patients with antiretroviral drug adverse reactions.

PMID- 24024327
TI  - Effect of a basic Chinese traditional diet in overweight patients.
AB  - OBJECTIVE: To evaluate the effect of a basic Chinese traditional diet (BTCD) in
      overweight patients on body mass index (BMI), lean mass, sense of hunger, and
      eating behaviour. METHODS: A total of 694 enrolled subjects (218 male and 476
      female) were divided into two groups: group A undergoing a 1200-Kcal BTCD, and
      group B undergoing a 1200-Kcal standard western diet. RESULTS: From T0 (before
      treatment) to T1 (6 weeks after treatment), BMI was lowered in group A from
      (32.33 +/- 5.51) to (31.96 +/- 5.56) kg/m2, and in group B from (31.62 +/- 6.29)
      to (31.36 +/- 6.47) kg/m2. After treatment, patients in group A lost more weight
      (0.37 +/- 0.52) kg than group B (0.26 +/- 0.79) kg (P = 0.0044). From T0 to T1,
      the mean lean mass of group A decreased from (16.48 +/- 5.50) to (16.27 +/- 5.45)
      kg. In group B, mean lean mass decreased from (16.93 +/- 6.49) to (16.44 +/-
      6.29) kg. The difference was significant (P = 0.0078). CONCLUSION: The two diets
      could lead to lower BMI, improve lean mass as well as eating behaviour and sense
      of hunger. However, the BTCD was significantly better than the western standard
      diet.

PMID- 24024328
TI  - Polyphyllin I inhibits proliferation and metastasis of ovarian cancer cell line
      HO-8910PM in vitro.
AB  - OBJECTIVE: To study the anticancer mechanism of polyphyllin I (PPI), a
      Traditional Chinese Medicine, on the ovarian cancer cell line HO-8910PM in vitro.
      METHODS: Transwell chamber invasive assays were used to investigate the
      inhibitory capacity of PPI on HO-8910PM metastasis. Gene expression profiling
      chips was used to screen differentially expressed genes between experiment group
      and control group. Reverse transcription PCR and Western blotting were used to
      determine mRNA and protein levels. RESULTS: With increasing PPI concentration,
      the metastatic capacity of cells decreased, with significance differences between
      the experimental and control groups (P < 0.01) as well as between two
      concentration groups. Gene expression profiling identified 123 differentially
      expressed genes, of which 70 were downregulated and 53 were upregulated. The
      genes were involved in multiple signal transduction pathways, including
      apoptosis, proliferation and metastasis. Real-time PCR (RT-PCR) showed that
      differential genes PIK3C2B, Caspase 9 and Wnt5A were downregulated with
      increasing PPI, showing an evident dose-effect relationship. The c-Jun was an
      exception. As the PPI dosage increased and the exposure time was extended, c-Jun
      relative expression showed an upward trend. There were significant differences
      between the experiment and control (P < 0.05). Western blot analyses showed that
      PPI treatment decreased levels of Caspase 9, Wnt5A and PIK3C2B and increased
      activated Caspase 9, c-Jun and p-c-Jun expression levels. CONCLUSION: PPI has
      strong antitumor and anti transfer activity. It can activate c-Jun expression and
      the JNK signaling pathway, elicit cell apoptosis via the mitochondrial-mediated
      Caspase activation pathway, and finally inhibit tumor growth and migration in
      vitro. The downregulation of PIK3C2B and Wnt5A jointly inhibit the proliferation
      and metastasis of HO-8910PM. PPI may be a novel treatment for ovarian cancer.

PMID- 24024329
TI  - Effect of yiqiyangyin recipe on heparanase and nephrin in rats with adriamycin
      induced nephropathy.
AB  - OBJECTIVE: To discuss the mechanism of Yiqiyangyin recipe in rats with adriamycin
      (ADR)-induced nephropathy. METHODS: We randomly divided 30 Sprague-Dawley rats
      into 5 groups: control, model, glucocorticoid, Chinese herb, and Chinese herb
      plus glucocorticoid groups. The 24-h urine volume was collected on days 7, 14,
      21, and 28 after ADR injection, and all rats were killed on day 28. We measured
      the 24-h levels of urinary protein, serum cholesterol, and serum triglycerides,
      and renal function of all rats by using routine biochemical methods. Pathological
      changes in the rat kidneys were observed under light and electron microscopes.
      Heparanase (HPA) mRNA expression levels were measured using real-time
      fluorescence-quantitative polymerase chain reaction. Urine levels of HPA in all
      groups were measured using enzyme-linked immunosorbent assay. The expression of
      nephrin was detected by immunohistochemical staining and quantitatively analyzed
      using Motic image analysis 3.2 software. RESULTS: The levels of urinary protein
      and serum triglycerides and cholesterol in rats with ADR-induced nephropathy
      increased on day 14. The serum albumin levels simultaneously decreased. All the
      changes reached the peak on day 28. Examination under the light microscope showed
      inflammatory cells and slight fibroplasia in the renal interstitium in the model
      group, but fewer inflammatory cells were observed in the intervention groups than
      those in the model group. Examination under the electron microscope showed
      extensive fusion of foot processes in ADR rats. HPA mRNA expression was higher in
      the model group than that in the control group. The HPA mRNA levels in the
      intervention groups, especially in the Chinese herb group, and Chinese herb plus
      glucocorticoid group were significantly lower than the level in the model group.
      The HPA expression levels correlated significantly with the proteinuria level. No
      significant difference was found in the HPA level in urine between the
      intervention groups and the model group, whereas the model group had a higher
      urinary HPA level than the control group. Nephrin mRNA expression levels in the
      model group were higher than those in the control group. Nephrin mRNA expression
      levels were significantly lower in the intervention groups than that in the model
      group, especially the Chinese herb plus glucocorticoid group. Compared with the
      control group, the model group showed increased nephrin expression in the kidney.
      Nephrin levels in the other groups, especially in the Chinese herb plus
      glucocorticoid group, were significantly lower than that in the model group. The
      nephrin levels in the kidney were negatively correlated with the proteinuria
      level. CONCLUSION: Yiqiyangyin recipe could attenuate foot process injury
      particularly in combination with a steroid reduce the development of proteinuria
      possibly by inhibition of HPA in the kidney, and regulate the expression of
      nephrin in rats with ADR-induced nephropathy. Our study showed that treatment
      with Yiqiyangyin recipe plus glucocorticoid was better than a singular
      intervention, and we explored the pharmacological mechanism of this combination
      by biochemical and molecular biological analysis to provide a basis for clinical
      application.

PMID- 24024330
TI  - Effect of lingguizhugan decoction on myocardial nuclear factor kappa B protein
      expression in rats with chronic heart failure.
AB  - OBJECTIVE: To investigate the effect of Lingguizhugan decoction (LGZGD) on
      changes of cardiac structure and function, and its putative mechanism of action,
      by investigating mRNA and protein expression of myocardial nuclear factor kappa B
      (NF-kappaB), and the plasma content of NF-kappaB in rats with chronic heart
      failure. METHODS: The chronic heart failure (CHF) model in rats was induced by
      coronary artery ligation. Sham operation was performed in control rats. Six weeks
      after the procedure, rats were randomly classified into the various treatment
      groups: model CHF, Captopril (4.4 mg/kg), low LGZGD dose (2.1 g/kg), medium LGZGD
      dose (4.2 g/kg), and high LGZGD dose (8.4 g/kg). Treatments continued for 4
      consecutive weeks. Changes of hemodynamic indices were observed by the PowerLab
      data acquisition and analysis system. Morphological changes of myocardium were
      observed by hematoxylin and eosin staining, and Masson staining. The mRNA and
      protein expression of myocardial NF-kappaB were detected by reverse transcription
      polymerase chain reaction and western blotting, respectively. The plasma content
      of NF-kappaB was detected by enzyme-linked immuno-sorbent assay. RESULTS: CHF
      rats showed significant dysfunction in hemodynamic indices and in cardiac
      structure. Compared with the sham operation group, mRNA expression of myocardial
      NF-kappaB and plasma content of NF-kappaB of the model group was significantly
      increased. All three doses of LGZGD, and Captopril, improved the hemodynamic
      dysfunction, and inhibited the change of cardiac structure while significantly
      improving the survival rate. Furthermore, compared with the model group, mRNA
      expression of myocardial NF-kappaB and plasma content of NF-kappaB were
      significantly reduced by all dosage groups of LGZGD as well as the Captopril
      group. CONCLUSION: In CHF rats, LGZGD improves changes of cardiac structure and
      function via its inhibition of NF-kappaB.

PMID- 24024331
TI  - Fangjihuangqi tang improved lower urinary tract dysfunction in benign prostatic
      hyperplasia rats model.
AB  - OBJECTIVE: To investigated the effect and mechanism of Fangjihuangqi Tang (FHT)
      on lower urinary tract dysfunction induced by benign prostatic hyperplasia (BPH)
      in rats. METHODS: Male rats were randomly divided into seven groups: normal,
      model, finasteride (0.5 mg/ kg), terazosin (0.5 mg/kg), and FHT (10, 5, 2.5
      g/kg). Rats were administered testosterone (0.5 mg sc) for 6 weeks after
      orchiectomy, excluding the normal group. All rats were intragastrically
      administered assigned drugs for 4 weeks from the third week. Urodynamics were
      assessed in rats under anesthesia. Serum dihydrotestosterone (DHT) and prostatic
      acid phosphatase (PAP) were measured. The prostate index (PI), bladder index
      (BI), and pathological detection were evaluated. RESULTS: In the model group, the
      PI, BI, serum DHT, serum PAP, threshold pressure (TP), micturition pressure (MP),
      and residual urine volume (RV) were significantly higher. Moreover, inter
      micturition duration (IMD) was significantly lower and the prostatic and bladder
      showed obvious pathological changes. The IMD was significantly higher, while BI,
      TP, MP, and RV were significantly lower and bladder pathological changes were
      alleviated in the FHT (10, 5 g/kg), finasteride, and terazosin groups. The PI,
      DHT, and PAP were significantly lower in the finasteride group, but they did not
      change significantly in the FHT (10, 5, 2.5 g/kg) and terazosin groups.
      CONCLUSION: FHT could relieve symptoms of lower urinary tract dysfunction in BPH
      rats but with no apparent effect on reducing the volume of the enlarged prostate
      itself.

PMID- 24024332
TI  - Effect of aqueous extract of sanweitanxiang powder on calcium homeostasis protein
      expression in ischemic-reperfusion injury rat heart.
AB  - OBJECTIVE: To investigate the underlying mechanism of reduced myocardial ischemia
      reperfusion (I/R) injury in rats using the traditional Tibetan medicine
      Sanweitanxiang powder (SWTX). METHODS: Rats were randomly divided into six groups
      (n = 10) as follows: (a) propranolol dinitrate control group, given propranolol
      dinitrate 0.02 g/kg for 10 days before I/R, (b) SWTX with a high dose group,
      given SWTX 1.5 g/kg for 10 days before I/R, (c) SWTX with a medium dose group,
      given SWTX 1.25 g/kg for 10 days before I/R, (d) sham group (Sham), in which the
      rat heart was exposed by pericardiotomy but without I/R, (e) SWTX with a low dose
      group, given SWTX 1.0 g/kg for 10 days before I/R, and (f) I/R injury group. Rats
      were intragastrically pretreated with propranolol dinitrate or SWTX. After that,
      the operation to cause ischemia and reperfusion was conducted. The
      histopathologic changes of rat hearts were observed by hematoxylin and eosin
      staining and transmission electron microscopy. Ca2+ homeostasis protein
      expression was determined by western blot. RESULTS: After SWTX pretreatment, the
      development of ultrastructural pathological changes from IR injury was
      attenuated. A decrease in the expression of B-cell lymphoma 2 associated X
      protein, and an increase in the expression of B-cell lymphoma 2 were observed. An
      increased activation of extracellular signal regulated kinases were found.
      Compared with the sham group, the expression of sarcoplasmic reticulum calcium
      ATPase, phospholamban, and calsequestrin were all up-regulated after pretreatment
      with SWTX. CONCLUSION: The protective mechanism of SWTX pretreatment on
      myocardial I/R injury might be related to its effect on maintaining the balance
      of calcium homeostasis in rat heart.

PMID- 24024333
TI  - Effect of blocking Ras signaling pathway with K-Ras siRNA on apoptosis in
      esophageal squamous carcinoma cells.
AB  - OBJECTIVE: To study the effect of RNAi silencing of the K-Ras gene on Ras signal
      pathway activity in EC9706 esophageal cancer cells. METHODS: EC9706 cells were
      treated in the following six groups: blank group (no transfection), negative
      control group (transfection no-carrier), transfection group (transfected with
      pSilencer-siK-ras), taxol chemotherapy group, taxol chemotherapy plus no-carrier
      group, taxol chemotherapy plus transfection group. Immunocytochemistry, Reverse
      transcription-polymerase chain reaction and western blotting were used to analyze
      the expression of MAPK1 (mitogen-activated protein kinases 1) and cyclin D1 in
      response to siRNA (small interfering RNA) transfection and taxol treatment.
      RESULTS: K-Ras (K-Ras gene) siRNA transfection of EC9706 esophageal squamous
      carcinoma cells decreased the expression of K-Ras, MAPK1 and cyclin D1 at the
      mRNA and protein level. Reverse transcription-polymerase chain reaction indicated
      that the expression levels of MAPK1 and cyclin D1 mRNAs were significantly lower
      in the transfection group than in the blank group (P < 0.05). Western blotting
      showed that 72 h after EC9706 cell transfection, the expression levels of MAPK1
      and cyclin D1 proteins had decreased in all groups, and the expression levels in
      the transfection group were significantly inhibited as compared with the blank
      group. Apoptosis increased significantly in the transfection group or after
      addition of taxol as compared with the blank group and the no-carrier group. The
      degree of apoptosis in the taxol plus transfection group was more severe.
      CONCLUSION: Apoptosis increased significantly in EC9706 esophageal carcinoma
      cells after siRNA-mediated inhibition of Ras signaling, with the most obvious
      increase observed in the transfection plus taxol chemotherapy group. Ras
      knockdown therefore increased cellular sensitivity to the chemotherapeutic agent,
      taxol. Ras knockdown also down-regulated the expression of the downstream genes,
      MAPK1 and cyclin D1, thus inhibiting the growth, proliferation and metabolism of
      esophageal cancer cells.

PMID- 24024334
TI  - Effect of xixin decoction on O-linked N-acetylglucosamine glycosylation of tau
      proteins in rat brain with sporadic Alzheimer disease.
AB  - OBJECTIVE: To study the effects of Xixin decoction (XXD) on O-linked N
      acetylglucosamine (O-GlcNAc) glycosylation of tau proteins in rat brain with
      sporadic Alzheimer disease (SAD), and discuss its possible mechanism on
      prevention and treatment of SAD. METHODS: The rat model of SAD was established by
      intracerebroventricular injection of streptozotocin. The specific pathogen free
      male Sprague-Dawley rats were randomly divided into sham-operation group (S),
      model group (M), donepezil group (D), XXD at a low dose group (XL), XXD at a
      medium dose group (XM) and XXD at a high dose group (XH). After treatment and
      praxiology test, immunohistochemistry and western blotting were used to detect O
      GlcNAc glycosylation level of tau proteins in rat brain with SAD. O-GlcNAc
      glycosylation and expression of tau proteins were detected by O-GlcNAc-specific
      antibodies RL2 and CTD110.6. RESULTS: O-GlcNAc glycosylated proteins enriched by
      succinylated wheat germ agglutinin significantly improved in the hippocampus of
      SAD rats. The differences were statistically significant among XXD groups (P <
      0.05, P < 0.01), while no obvious differences were observed between D group and M
      group (P > 0.05). CONCLUSION: XXD can significantly improve O-GlcNAc
      glycosylation level of tau proteins in the hippocampus of SAD rats, which maybe
      inhibit hyperphosphorylation of tau proteins on key sites and its toxicity, and
      prevent the pathological process of SAD.

PMID- 24024335
TI  - Mechanism and effect of shijueming (Concha Haliotidis) on serum calcium in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: To observe the impact of Shijueming (Concha Haliotidis) on
      spontaneously hypertensive rats via blood pressure, serum calcium, vascular
      smooth muscle membrane L-type calcium channel alpha1 C subunit (CaL-alpha1C),
      plasma membrane calcium-ATPase (PMCA) mRNA expression, and the L-type calcium
      channel in vascular smooth muscle cells. METHODS: Twelve-week-old male rats with
      spontaneous hypertension were divided into three groups: a Shijueming (Concha
      Haliotidis) group (group 1), a nifedipine group (group 2), and a distilled water
      group (group 3). All were given a four-week treatment. Blood pressure and
      dissociative serum calcium were examined before treatment. Blood pressure was
      taken every week during treatment. Atomic absorption spectrometry was used to
      examine dissociative serum calcium. Reverse transcription-polymerase chain
      reaction was used to examine the expression of CaL-alpha1C and PMCA1 mRNA. The
      patch clamp technique was used to examine the electrophysiological
      characteristics of the vascular smooth muscle cell calcium channels. RESULTS:
      After treatment, blood pressure of the Shijueming (Concha Haliotidis) group
      lowered but not significantly (P > 0.05). Blood pressure of the nifedipine group
      lowered significantly (P < 0.05). Blood pressure of the distilled water group
      remained high. The concentration of serum calcium in the Shijueming (Concha
      Haliotidis) and the distilled water groups lowered (P < 0.05). Expression of CaL
      alpha1C mRNA in the nifedipine group decreased compared with the distilled water
      group (P < 0.01). There was the decreasing trend in the Shijueming (Concha
      Haliotidis) group, but it was not statistically significant. Shijueming (Concha
      Haliotidis) also had effects on the expression of PMCA1 mRNA but without
      statistical significance. However, there was a significant decreasing effect on
      vascular smooth muscle cell I(Ca)-L flow. CONCLUSION: This study indicated that
      Shijueming (Concha Haliotidis) could increase serum calcium and decrease blood
      pressure. It may work by influencing calcium channels, expression of PMCA1 mRNA,
      and regulating ion calcium channels and calcium-ATPase.

PMID- 24024336
TI  - Gene expression profiling of rat livers with yin-deficiency-heat syndrome.
AB  - OBJECTIVE: To explore the nature of "Yin internal heat caused by Yin-deficiency,"
      in terms of the theory of Traditional Chinese Medicine, by studying energy
      metabolism in rats with Yin-deficiency-heat syndrome and analyzing the gene
      expression profile of their livers. METHODS: A Yin-deficiency-heat syndrome model
      was induced in rats using three Chinese medicinal herbs. Glycogen and
      triglycerides in blood plasma, and the enzyme activity of ATP in livers were
      measured colorimetrically. Triiodothyronine (T3), thyroxine (T4), and thyroid
      stimulating hormone levels in blood plasma were also measured with enzyme linked
      immunosorbent assay. The gene expression profile of livers was detected with gene
      chip analysis. Differentially expressed genes were screened out and classified
      according to Gene Ontology. The accuracy of results were examined with reverse
      transcription-polymerase chain reaction. RESULTS: Compared with the control
      group, body weight (P < 0.05) and hepatic glycogen (P < 0.05) were significantly
      lower in the Yin-deficiency-heat syndrome group. Moreover, toe temperature (P <
      0.01) and triglyceride (P < 0.05), Na(+) -K(+)-ATPase (P < 0.01), Mg(2+)-ATPase
      (P < 0.01), T3 (P < 0.05), and T4 (P < 0.01) levels were significantly higher.
      There were 99 differentially expressed genes in livers from the Yin-deficiency
      heat syndrome group. Genes were mainly related to sterol synthesis (Pc = 0.0392),
      defense response (Pc = 0.0448), and sterol metabolism (Pc = 0.0533). CONCLUSION:
      Abnormal expression genes in rats with Yin-deficiency-heat syndrome prompted the
      synthesis and metabolism of cholesterol, increased energy consumption, and
      reduced defense response. This gene expression might be the molecular mechanism
      underlying "internal heat caused by Yin-deficiency" in the rats with Yin
      deficiency-heat syndrome.

PMID- 24024337
TI  - Effect of danhong injection on expressions of macrophage scavenger receptor 1 and
      sub-family A member 1 in human U937 cells.
AB  - OBJECTIVE: To study the effects of Danhong injection (DHI) on expression of the
      macrophage scavenger receptor 1 (MSR1) and ATP-binding cassette, sub-family A
      member 1 (ABCA1) genes, which encode scavenger receptor-A I (SR-AI) and ATP
      binding cassette transporter 1 (ABCA1), respectively, as a potential anti
      atherosclerotic mechanism. METHODS: Human U937 cells were stimulated by
      incubation with 100 nM phorbol 12-myristate 13-acetate (PMA) for 48 h. These
      stimulated, monocyte-like cells were then incubated for 24 h with 50 mg/L
      oxidized low-density lipoprotein (ox-LDL, to induce foam cell formation),
      together with a liver X receptor (LXR) agonist or with different DHI
      concentrations. MSR1 and ABCA1 mRNA levels were measured by fluorescence-based
      quantitative PCR. RESULTS: Compared with control cells (which received only ox
      LDL), cells treated with both ox-LDL and 10 micromol/L LXR agonist showed lower
      MSR1 expression (but this effect was not statistically significant, P > 0.05) and
      higher ABCA1 expression (P < 0.01). Cells that received ox-LDL and 3 mL/L DHI
      possessed higher MSR1 mRNA levels than the controls, whereas cells treated with
      ox-LDL and higher DHI concentrations (10, 30 or 60 mL/L) showed lower MSR1
      expression levels (but the differences observed between DHI concentration groups
      were not statistically significant, P > 0.05). ABCA1 expression in cells treated
      with ox-LDL and 3, 10 or 30 mL/L DHI was higher than in the control cells, and
      increased with increasing DHI concentration (P < 0.05). ABCA1 expression in cells
      treated with ox-LDL and the highest DHI concentration tested (60 mL/L) was not
      significantly different from that in the controls. ABCA1 mRNA levels in cells
      treated with ox-LDL and DHI were similar to, or lower than, those in cells
      treated with ox-LDL and the LXR agonist. CONCLUSION: DHI does not affect MSR1
      mRNA levels in ox-LDL-treated U937 cells. However, at certain concentrations (10
      and 30 mL/L), DHI significantly increases ABCA1 mRNA levels. Therefore, the anti
      atherosclerotic action of DHI might be mediated by an increased expression of
      ABCA1.

PMID- 24024338
TI  - Effect of tangnaikang on TGF-beta1-induced transdifferentiation of human renal
      tubular epithelial HK-2 cells.
AB  - OBJECTIVE: To explore the function of Tangnaikang (TNK) in the prevention and
      treatment of renal interstitial fibrosis through transdifferentiation of the
      human renal tubular epithelial cell line HK-2 induced by transforming growth
      factor-beta1 (TGF-beta1). METHODS: HK-2 cells cultured in dulbecco's modified
      eagle medium/F12 (1 : 1) with 10% fetal calf serum were divided into six groups:
      blank control group, TGF-beta1 group (TGF-beta1 10 ng/mL), serum control group
      (TGF-beta1 10 ng/mL + 10% serum), treatment group 1 (TGF-beta1 10 ng/mL + 5% TNK
      serum), treatment group 2 (TGF-beta1 10 ng/mL + 10% TNK serum), and treatment
      group 3 (TGF-beta1 10 ng/mL + 20% TNK serum). Cell proliferation was detected by
      4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Expression of
      alpha-smooth muscle actin (alpha-SMA) and E-cadherin were observed by
      immunohistochemical assay. The contents of collagen I (Col I), collagen III (Col
      III), and fibronectin (FN) in the culture medium supernatant were detected by
      ELISA. RESULTS: E-cadherin was expressed and alpha-SMA was not expressed in
      normal HK-2 cells. In HK-2 cells cultured with TGF-beta1, alpha-SMA expression
      significantly increased, HK-2 cells significantly proliferated, and secretion of
      Col I, Col III, and FN significantly increased compared with the blank control
      group (all P < 0.05). In the HK-2 cells cultured with TGF-beta1 and TNK serum,
      the expression of alpha-SMA significantly decreased, the expression of E-cadherin
      significantly increased, and the cell proliferation and the secretion of Col I,
      Col III and FN were significantly inhibited compared with the TGF-beta1 group
      (all P < 0.05). CONCLUSION: TNK can inhibit cell proliferation and reduce
      secretion of Col I, Col III, and FN. This indicates that TNK can inhibit
      transdifferentiation of human renal tubular epithelial cells induced by TGF
      beta1, with the effect of preventing and treating renal interstitial fibrosis.

PMID- 24024339
TI  - Effect of zibushenjing fang on skeletal development and brain tissue
      antioxidation in mice with kidney essence insufficiency: a mechanistic study.
AB  - OBJECTIVE: To investigate the effects of Zibushenjing Fang (formula for tonifying
      the kidney essence) on skeletal development and brain tissue antioxidation in
      mice with kidney essence insufficiency. METHODS: Fifty male Kunming mice were
      randomly divided into five groups: normal group, model group, Jinkuishenqi Wan
      group, Zibushenjing Fang high dose group, and Zibushenjing Fang low dose group,
      with 10 mice in each group. The model of kidney essence insufficiency syndrome
      was established in all the mice except the normal group by using a cat to
      threaten the mice and by swimming until exhaustion daily which lasted about 21
      days. Mice in the model group were administered 20 mL/ kg(-1) x d(-1) of normal
      saline intragastrically. The Jinkuishenqi Wan group was given 2.7 g/kg(-1) x d(
      1) of a solution of Jinkuishenqi Wan. The Zibushenjing Fang high dose group was
      given 20 g/kg(-1) x d(-1) and the Zibushenjing Fang low dose group was given 10
      g/kg(-1) x d(-1) of a solution of Zibushenjing Fang. The general condition of all
      the groups was observed, including the quantity of food and water intake,
      swimming time, length of femur, and weight of the femur and musculus quadriceps
      femoris. The total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px),
      and methane dicarboxylic aldehyde (MDA) activities in the brain tissues were
      detected. RESULTS: Zibushenjing Fang could improve the manifestation of kidney
      essence insufficiency, increase the quantity of food and water intake, swimming
      time, femur length, and femur and musculus quadriceps femoris weight. It could
      also regulate the activities of T-SOD, GSH-Px, and MDA in brain tissue.
      CONCLUSION: Zibushenjing Fang may play an important role in treating kidney
      essence insufficiency syndrome by promoting body development and improving brain
      tissue antioxidation.

PMID- 24024340
TI  - Effects of combined acupuncture and eugenol on learning-memory ability and
      antioxidation system of hippocampus in Alzheimer disease rats via olfactory
      system stimulation.
AB  - OBJECTIVE: To investigate the effects of combined acupuncture and eugenol on
      learning-memory ability and the antioxidation system of the hippocampus in
      Alzheimer disease (AD) rats. METHODS: Sixty Sprague Dawley rats, weighing (300 +/
      10) g, were randomly divided with 10 rats per group into a normal control group,
      AD model group, AD with cut olfactory nerve group, Xiu three-needle group,
      eugenol group, and combined acupuncture and eugenol group. The AD model was
      established by injection of amyloid beta1-40 (Abeta 1-40). Morris maze tests were
      conducted for evaluating the learning-memory ability. Content of malondialdehyde
      (MDA) and activities of superoxide dismutase (SOD) and glutathione peroxidase
      (GSH-Px) in the hippocampus were detected. RESULTS: The average escape latency
      and the mean swimming distance in the normal control group, the Xiu three-needle
      group, the eugenol group, and the combined acupuncture and eugenol group were
      significantly shorter than those in the AD model group (all P < 0.01). The
      combined acupuncture and eugenol group had shorter escape latency and mean
      swimming distance than those in the Xiu three-needle group and the eugenol group.
      There were no significant differences between the Xiu three-needle group and the
      eugenol group and between the AD group and the AD with cut olfactory nerve group
      (P > 0.05). Compared with the normal control group, the MDA content in the
      hippocampus significantly increased (P < 0.05) and GSH-Px and SOD activities
      significantly decreased in the AD model group (P < 0.01). Compared with the AD
      model group, significantly decreased (P < 0.01) and SOD and GSH-Px activities
      significantly increased in the Xiu three-needle group, eugenol group, and
      combined acupuncture and eugenol group (P < 0.05). Compared with the Xiu three
      needle group and eugenol group, the MDA content significantly decreased (P <
      0.05) and SOD and GSH-Px activities increased (P < 0.05) in the combined
      acupuncture and eugenol group. There were no significant differences among the
      three indices between the Xiu three-needle group and the eugenol group and
      between the AD model group and the AD with cut olfactory nerve group (P > 0.05).
      CONCLUSION: Both Xiu three-needle and eugenol can increase learning-memory
      ability, decrease MDA content, and increase SOD and GSH-Px activities in the
      hippocampus in AD rats. The combination of acupuncture with eugenol has stronger
      effects, and the effects depend on the olfactory pathway.

PMID- 24024341
TI  - Review of controlled clinical trials on acupuncture versus sham acupuncture in
      Germany.
AB  - OBJECTIVE: To examine German controlled clinical trials on the therapeutic
      effects of acupuncture vs sham acupuncture, and to find whether there are
      problems with the conclusion that sham acupuncture has no significant deviation
      from acupuncture. METHODS: We focused on literature from the last ten years (2002
      2011) included in PubMed about controlled clinical trials on acupuncture vs sham
      acupuncture carried out in Germany. The methods applied in sham acupuncture are
      summarized, and the difference between the acupuncture and sham groups were
      analyzed. We measured effects based on the following criteria: acupuncture is
      effective and superior to sham, acupuncture is effective but similar to sham,
      both of them have uncertainty regarding treatment effect, or no significant
      effect. Finally, we reviewed the hypotheses of different scholars on sham
      acupuncture and analyzed their results. RESULTS: Four types of controlled
      clinical trials including sham acupuncture on non-Traditional Chinese Medicine
      acupoints, minimal acupuncture on non-acupoints, placebo needle and sham laser
      acupuncture had varying results in the 57 articles analyzed. Some showed that
      acupuncture had a better effect than sham, while some suggest acupuncture and
      sham had similar effects. In all studies using sham acupuncture on non
      therapeutic points, sham electrodes, and sham electro-acupuncture, the
      therapeutic effect was better than sham. Of the trials, 37 demonstrated that
      acupuncture had a better effect than sham acupuncture. Only nine trials found no
      significant difference between acupuncture and sham. Two controlled trials for
      the same condition (neck pain) conducted by two different German research
      institutes used the same control method, but reached contradictory conclusions.
      CONCLUSION: We found problems in conclusions based on results of controlled
      clinical trials of sham acupuncture in Germany. Therefore, there is still not
      enough evidence to support the statements that "acupuncture and sham acupuncture
      have no difference in treatment effect" and "acupuncture is just a placebo
      effect." The control methods of sham acupuncture used in Germany may not be
      standardized and may not be suitable for acupuncture clinical trial research. We
      suggest that research on the methodology of sham acupuncture should be given
      priority in the design of acupuncture trials in the future.

PMID- 24024342
TI  - Status and strategies analysis on international standardization of auricular
      acupuncture points.
AB  - OBJECTIVE: To supply literature for developing an international standard of
      auricular acupuncture points. METHODS: Electronic database searches were
      conducted in the Chinese National Knowledge Infrastructure and VIP, and the
      Western databases, Pubmed, the National Science and Technology Library, and the
      German Journal of Acupuncture, from 1990 to April, 2012. We also searched the
      documents of international symposiums for auricular acupuncture points (AAPs).
      Keywords were "auricular points", "auricular acupuncture points", "ear points",
      or "auriculotherapy". RESULTS: Basic and clinical research on AAPs was performed
      in China, the United States, France, and Germany. Clinical AAP research was done
      in Italy, Austria, Switzerland, Spain, the UK, Holland, Japan, Russia, and
      Africa. However, AAP research was not communicated internationally. The World
      Federation of Acupuncture-Moxibustion Societies recommended international
      standard of auricular acupuncture points (ISAAPs). Standardized nomenclature and
      locations of AAPs would provide a solid basis to draft an international standard
      organization. CONCLUSION: Experts need to find common points from different
      countries or regions, provide evidence of different ideas, and list the proposal
      as a recommendation for an international standard.

PMID- 24024343
TI  - Pharmacological effects of Astragaloside IV: a literature review.
AB  - OBJECTIVE: To review the pharmacological effects and mechanisms of action of
      Astragaloside IV in Huangqi (Radix Astragali Mongolici). METHODS: Aticles
      focusing on Astragaloside IV in English and Chinese in databases were collected
      and reviewed in order to summarize the latest extraction separation,
      pharmacokinetics, and the pharmacological effects of astrageloside IV. RESULTS:
      Protective effects of Astrageloside IV on the cardiovascular system, immune,
      digestive, nervous system were identified, and the action mechanisms were
      associated with regulation of the calcium balance, anti-oxydant, antiapoptosis,
      antivirus, and so on. CONCLUSION: Astrageloside IV has broad application
      prospects, especially in cardiovascular diseases, digestive diseases, cancer and
      other modern high incidence, high-risk diseases, and could be developed as a
      medicine.

PMID- 24024344
TI  - Women's health--respect at last.

PMID- 24024345
TI  - 'Total woman' program engages members with health.

PMID- 24024346
TI  - Getting to the heart of disparities in care.

PMID- 24024347
TI  - Postpartum 'normalcy' can be elusive.

PMID- 24024348
TI  - Focusing on midlife: an oft-neglected stage.

PMID- 24024349
TI  - Meeting women's needs brings success downtown.

PMID- 24024350
TI  - A hospital-based domestic violence program is crucial to keeping women safe.

PMID- 24024351
TI  - SANE program fights stigma of sexual assault.

PMID- 24024352
TI  - Excerpts from Julie's journal.

PMID- 24024353
TI  - Downsizing for reform: how does church teaching guide us?

PMID- 24024354
TI  - Scripture's paralytic and our mission.

PMID- 24024355
TI  - 'A heart which sees': on being neighbor.

PMID- 24024357
TI  - Medical mission and immersion trips: is intent dovetailing outcomes?

PMID- 24024356
TI  - Healthier environments as a worthy program goal.

PMID- 24024358
TI  - Effect of air pollution control on mortality and hospital admissions in Ireland.
AB  - During the 1980s the Republic of Ireland experienced repeated severe pollution
      episodes. Domestic coal burning was a major source of this pollution. In 1990 the
      Irish government introduced a ban on the marketing, sale, and distribution of
      coal in Dublin. The ban was extended to Cork in 1995 and to 10 other communities
      in 1998 and 2000. We previously reported decreases in particulate black smoke
      (BS*) and sulfur dioxide (SO2) concentrations, measured as total gaseous acidity,
      in Dublin after the 1990 coal ban (Clancy et al. 2002). In the current study we
      explored and compared the effectiveness of the sequential 1990, 1995, and 1998
      bans in reducing community air pollution and in improving public health. We
      compiled records of daily BS, total gaseous acidity (SO2), and counts of cause
      specific deaths from 1981 to 2004 for Dublin County Borough (1990 ban), county
      Cork (1995 ban), and counties Limerick, Louth, Wexford, and Wicklow (1998 ban).
      We also compiled daily counts of hospital admissions for cardiovascular,
      respiratory, and digestive diagnoses for Cork County Borough (1991 to 2004) and
      counties Limerick, Louth, Wexford, and Wicklow (1993 to 2004). We compared pre
      ban and post-ban BS and SO2 concentrations for each city. Using interrupted time
      series methods, we estimated the change in cause-specific, directly standardized
      mortality rates in each city or county after the corresponding local coal ban. We
      regressed weekly age- and sex-standardized mortality rates against an indicator
      of the post- versus pre-ban period, adjusting for influenza epidemics, weekly
      mean temperature, and a season smooth of the standardized mortality rates in
      Coastal counties presumably not affected by the bans. We compared these results
      with similar analyses in Midlands counties also presumably unaffected by the
      bans. We also estimated the change in cause-specific, directly standardized,
      weekly hospital admissions rates normalized for underreporting in each city or
      county after the 1995 and 1998 bans, adjusting for influenza epidemics, weekly
      mean temperature, and local admissions for digestive diagnoses. Mean BS
      concentrations fell in all affected population centers post-ban compared with the
      pre-ban period, with decreases ranging from 4 to 35 microg/m3 (corresponding to
      reductions of 45% to 70%, respectively), but we observed no clear pattern in SO2
      measured as total gaseous acidity associated with the bans. In comparisons with
      the pre-ban periods, no significant reduction was found in total death rates
      associated with the 1990 (1% reduction), 1995 (4% reduction), or 1998 (0%
      reduction) bans, nor for cardiovascular mortality (0%, 4%, and 1% reductions for
      the 1990, 1995, and 1998 bans, respectively). Respiratory mortality was reduced
      in association with the bans (17%, 9%, and 3%, respectively). We found a 4%
      decrease in hospital admissions for cardiovascular disease associated with the
      1995 ban and a 3% decrease with the 1998 ban. Admissions for respiratory disease
      were not consistently lower after the bans; admissions for pneumonia, chronic
      obstructive pulmonary disease (COPD), and asthma were reduced. However,
      underreporting of hospital admissions data and lack of control and comparison
      series tempered our confidence in these results. The successive coal bans
      resulted in immediate and sustained decreases in particulate concentrations in
      each city or town; with the largest decreases in winter and during the heating
      season. The bans were associated with reductions in respiratory mortality but no
      detectable improvement in cardiovascular mortality. The changes in hospital
      admissions for respiratory and cardiovascular disease were supportive of these
      findings but cannot be considered confirming. Detecting changes in public health
      indicators associated even with clear improvements in air quality, as in this
      case, remains difficult when there are simultaneous secular improvements in the
      same health indicators.

PMID- 24024359
TI  - [Survey on the consumption status of trans fatty acids food among the population
      over the age of 3 in Beijing and Guangzhou].
AB  - OBJECTIVE: To investigate the intakes of trans fatty acids over the age of 3 in
      different populations, and to determine the high exposure food and population in
      two cities. METHODS: Use food frequency survey to investigate the frequency and
      the average intake of food containing trans fatty acids among subjects in the
      past three months. RESULTS: The first ranks high exposure food is vegetable oil,
      while other food is different in sequence among two cities. The common high
      exposure populations are 13-17 years old groups and students at school groups.
      CONCLUSION: The high exposure food and population are different among two cities,
      and the reasons are so various that we need further research.

PMID- 24024360
TI  - [Effects of the body fat mass and blood sugar and plasma resistin to slim
      exercise prescription for overweight and obesity students].
AB  - OBJECTIVE: To explore the influences of slim exercise prescription on body fat
      mass, blood sugar and plasma resistin for overweight and obesity students.
      METHODS: Subjects were 9 males and 13 females for simple overweight and obesity
      students of freshman and junior. The function capacity (FC) were defined after
      examine of body shape, physical function and exercise capacity. The slim goals
      and exercise projects were determined according to different objects. The
      exercise intensity was 60%-70% of FC and 13-15 levels of RPE. Exercise with each
      time was 60 min, exercise frequency was 5 times perweek, energy metabolism was
      500-600 kcal at a time. The relative indexes were detected after 8 weeks.
      RESULTS: Implementing programmes of slim exercise prescription for 8 weeks,
      before and after the experiment in the males and females group. The weight, BMI,
      percentage of body fat (FAT%), waist and hip circumference ratio (WHR), body
      surface area (BS), fat indexes, the density of body for overweight and obesity
      the male and female students were significantly decreased (P < 0.01). Body fat
      mass (FM) and blood sugar were significantly decreased (P < 0.01). Plasma
      resistin of the male students were significant different (P < 0.01), but the
      female students were significant different (P < 0.05). Analysis of Bivariate
      Correlation was Pearson Correlation, plasma resistin and BMI, WHR the male
      students had correlation, but the female had no correlation. CONCLUSION: The
      exercise prescription was safe and sure, and could improve weight, BMI, FAT%, FM,
      WHR, BS, fat indexes, the density of body, blood sugar, plasma resistin in
      obesity without the diet control.

PMID- 24024361
TI  - [Effects of bisphenol A on testis testosterone synthesis in mouse cultured in
      vitro].
AB  - OBJECTIVE: To investigate the effects of BPA on testosterone synthesis and the
      related genes expression in the fetal testis of male mouse by organ culture in
      vitro. METHODS: The testis tissues cultured in vitro were randomly divided into
      five groups, DMSO control group and 4 different concentration of BPA groups (10(
      7), 10(-6), 10(-5) and 10(-4) mol/L respectively). The culture medium and gas
      were changed every 24 h. The histomorphological examination of the testis was
      conducted under optical microscope, the testosterone levels in the cultured
      medium were measured by radioimmunoassay, the expressions of related proteins
      were measured by immunohistochemistry, and the expression of 3betaHSD, P450scc,
      P450c17 and Vimentin were determined by real-time PCR. RESULTS: Compared to the
      control group, the number of sertoli cells were decreased and flocculent changes
      appear in some Leydig ceils in 10(-) mol/L dose group. Testosterone secretion was
      gradually reduced as time goes on. The testosterone synthesis of 10(-5) mol/L
      dose group was increased in 48h (P < 0.05), and the rest groups were decreased,
      especially the 10(-4) mol/L dose group (P < 0.1). The expression of genes coding
      for proteins involved in testosterone biosynthesis, 3betaHSD, P450scc, P450c17
      and Vimentin were reduced. CONCLUSION: Bisphenol A can affect testosterone
      synthesis of mouse cultured in vitro through suppression of 3betaHSD ,P450scc,
      P450c17 and Vimentin.

PMID- 24024362
TI  - [Inhibitory effects of exogenous zinc on enzymatic activity of tumor suppressor
      protein PTEN and possible mechanisms in human airway epithelial cells].
AB  - OBJECTIVE: To examine the effect of exogenous zinc on enzymatic activity of tumor
      suppressor PTEN and underlying mechanisms. METHODS: Human airway epithelial cells
      (BEAS-2B) were employed as the in vitro model. Enzymatic activity of PTEN was
      measured using malachite green colorimetric assay and immunoblotting. Moreover,
      the activity of casein kinase-2 (CK-2), the upstream kinase of PTEN, was
      determined. RESULTS: Exposure of BEAS-2B cells to Zn2+ inhibited phosphatase
      activity of PTEN, as well as PTEN phosphorylation, indicative of PTEN activity (P
      < 0.05). Under the same experimental condition, Zn2+ stimulation resulted in
      significant reduction of CK-2 activity (P < 0.05). In addition, CK-2 was shown to
      induce PTEN phosphorylation (P < 0.05). CONCLUSION: These results suggested that
      Zn2+ exposure might inhibit PTEN phosphatase activity through inhibition of CK-2
      activity in human airway epithelial cells.

PMID- 24024363
TI  - [Effects of ozone and fine particulate matter (PM2.5) on rat cardiac autonomic
      nervous system and systemic inflammation].
AB  - OBJECTIVE: To study the effects of ozone and fine particulate matter (PM2.5) on
      rat cardiac autonomic nervous system and systemic inflammation and the
      interconnected relationship of these two pathways. METHODS: 48 Wistar rats were
      randomly assigned to 8 groups (n = 6). Rats were intratracheal instillation of
      0.2, 0.8 and 3.2 mg/rat PM2.5 as low-dose, medium-dose and high-dose PM2.5 alone
      exposure groups. Ozone combined PM2.5 groups were exposed to 0.8 ppm ozone 4
      hours and then instilled 0.2, 0.8 and 3.2 mg/rat PM2.5 separately. Rats only
      inhaled 0.8 ppm ozone for 4 hours as ozone alone exposure group. Control rats
      were instilled with saline. Each exposure protocol applied twice a week for three
      continuous weeks. Systolic blood pressure and electrocardiograph (ECG) morphology
      of rats were recorded at 24 hours post-exposure of the last exposure. Serum TNF
      alpha, IL-6 and CRP were analyzed. Right ventricles were used as pathological
      examination with HE staining. RESULTS: HRV indices in PM2.5 alone and combined
      exposure groups showed significant difference compared to control. However, heart
      rate only reduced significantly in ozone combined PM2.5 groups. Blood pressure
      rose significantly in combined groups and high-dose PM2.5 alone exposure. TNF
      alpha and IL-6 increased significantly in PM2.5 alone/and ozone groups. CRP
      showed obvious dose-dependent relationship in PM2.5 alone and combined groups.
      Cardiac histopathology results revealed that PM2.5 deposition and myocardial
      inflammation were also observed in high-dose PM2.5 rats. CONCLUSION: Ozone can
      enhance the cardiac autonomic nervous system and systemic inflammation induced by
      PM2.5.

PMID- 24024364
TI  - [Effects of cold air activity on serum catecholamine level in patients with
      cardiovascular or cerebrovascular disease].
AB  - OBJECTIVE: To study the influence on serum catecholamine (CA) in process of cold
      air activities. METHODS: Residents of Zhangye City in Gansu Province were
      selected by means of random cluster sampling. Dopamine (DA), adrenaline (AD),
      norepinephrine (NE) were measured before, in the transit and after the cold air
      transit. RESULTS: The DA of cases and control group have notable changes before,
      in and after the cold air transit, statistics test have significant difference (P
      < 0.05), multiple comparison have significant difference (P < 0.05) in DA changed
      obviously (P < 0.05) of control group. Before and mid cold air activity, the DA
      and NE level have the differences of case group. CONCLUSION: The cold air
      activities have the influence on catecholamine level in health people and
      patients. DA and NE may play the critical role in disease happening.

PMID- 24024365
TI  - [Study on the prevalence of dyslipidemia and associated dietary risk factors
      among adults in Shunyi District of Beijing].
AB  - OBJECTIVE: To study the prevalence of dyslipidemia and explore dietary related
      factors of dyslipidemia among residents aged over 18-year-old in Shunyi District
      of Beijing. METHODS: A stratified cluster random sampling was used in this study
      which select the residents who aged above 18 years old in Shunyi District to do a
      well-designed questionnaire and physical examination, the cholesterol (TC),
      triglycemide (TG), low density lipoprotein cholesterol (LDL-C) and high density
      lipoprotein cholesterol (HDL-C) were measured and statistical processed in order
      to analyze the differences of dietary influencing factors between the
      dyslipidemia and normal population. RESULTS: The detection rates of dyslipidemia
      and combined dyslipidemia in Shunyi adults were 49.3% and 2.7%. The adults'
      intake of energy, fat and carbohydrate in rural areas was significantly higher
      than that in urban residents (P < 0.05). The intake of sodium, vegetable oil and
      salt all exceeded the standard of Dietary Guidelines for Chinese. There were
      significant difference in the contribute rate of fat and carbohydrate in total
      energy between the the dyslipidemia and normal population. The multi-factor
      Logistic Analysis showed that higher BMI, waist circumference, weight, fat,
      cholesterol were the risk factors of dyslipidemia, dietary niacin and vitamin C
      are protective factors for adults' dyslipidemia. CONCLUSION: The dyslipidemia
      among residents in Shunyi District of Beijing and their Dietary Structure is
      closely related. The unreasonable dietary structure and lifestyle maybe the main
      factor of dyslipidemia.

PMID- 24024366
TI  - [Investigation of nutritional status of pupils and dietary survey in primary
      schools in poor counties of Guangxi and Yunnan].
AB  - OBJECTIVE: To understand the nutritional status of pupils and to provide basic
      evidence for the nutritional interventions. METHODS: The subjects of the study
      were 2046 pupils from 9 primary schools in poor counties of Guangxi and Yunnan.
      The contents of the investigation included medical physical examination,
      haematoglobin determination and dietary survey. Nutritional Status was evaluated
      according to WHO growth standards. RESULTS: The prevalence of stunting and
      wasting in children from 6 to 14 years old in poor areas of Guangxi and Yunnan
      were 34.3% and 6.5% respectively. The anemia prevalence of them was 20.5%. The
      diet provided by the canteens of local school was mainly composed of plant food.
      Animal food was deficient. The cooking oil in local school was most of lard oil.
      The per pupil average daily intake of energy, protein, thiamin, riboflavin,
      vitamin C and calcium was 1491.29 kcal, 36.36 g, 179.15 ug, 0.57 mg, 0.37 mg,
      53.67 mg and 163.14 mg respectively, which were lower than RNI or Al. CONCLUSION:
      The chronic malnutrition of pupils in poor areas is still serious. The variety of
      food provided by the canteens of local school is quite single, and the quality of
      the meals is low. Intakes of energy, protein and micronutrient from school diet
      are insufficient for pupils.

PMID- 24024367
TI  - [Applicating food frequency questionnaire to assess the relationship between
      dietary polyunsaturated fatty acid intake and hypertension, dyslipidemia of Pumi
      nationality].
AB  - OBJECTIVE: The relationship between dietary polyunsaturated fatty acid intake and
      hypertension, dyslipidemia of Pumi nationality was studied,which provides a
      scientific basis of prevention and cure of hypertension and dyslipidemia.
      METHODS: A total of 376 Pumi nationality residents over 18 years in Lanping Bai
      Pumi nationality County of Nujiang state in Yunnan Province were selected as the
      research object, and a variety of food intake, intake frequency, the history of
      present illness and family history in recent years were collected by
      questionnaire survey. The blood pressure was measured. The fasting blood of the
      respondents was collected to detect triglyceride (TG) , cholesterol (TC), low
      density lipoprotein (LDL-C) and high density lipoprotein (HDL-C). RESULTS: The
      Pumi nationality residents' dietary fat intake was high, accounted for 198.5% of
      RNI. Energy ratio of three large capacity nutrient were imbalanced, but the per
      capita intake of n-3PUFA, EPA, DHA were not high. Hypertension prevalence of the
      Pumi nationality residents was 15.4%. Dyslipidemia type main performs that low
      high-density lipoprotein occupying 54. 8% , hypercholesterolemia occupying 8% ,
      hypertriglyceridemia occupying 19.1%, and TC or TG anomaly crowd occupying 25%.
      PUFAs and dyslipidemia, n-6PUFA and hypertension were both showed a negative
      correlation. CONCLUSION: In order to prevent the occurrence and development of
      cardiovascular disease, to reduce blood lipids, the Pumi nationality residents
      should reduce the intake of grease and food rich in fat, and increase the intake
      of food rich in DHA, EPA.

PMID- 24024368
TI  - [Study on normal ranges of thyroglobulin of total population in iodine-replete
      region of China].
AB  - OBJECTIVE: To deduce normal ranges of thyroglobulin of total population in iodine
      replete region by determining the human serum thyroglobulin in normal population
      of part full iodine region. METHODS: Typical survey was used in this present
      study. Children aged 8-10 years, adults aged 18-45 years, pregnant woman and
      lactating women were chosen as our subjects. Morning fasting blood samples of
      subjects were collected. Thyroglobulin and thyroid function were determined, and
      the measured value of those subjects with normal thyroid function was analyzed.
      RESULTS: The normal ranges of thyroglobulin of the subjects were as following:
      Children aged 8-10 years: male (1.40, 10.18) microg/L,female (1.41, 11.44)
      microg/L, adults aged 18-45 years: male (1.55, 39.88) microg/L, female (1.44,
      23.22) microg/L, pregnant woman: (0.94, 11.91) microg/L, lactating women: (0.12,
      15.05) microg/L. CONCLUSION: The research confirmed the serum Tg normal reference
      of different populations under the adequate iodine level, regarding this, Tg was
      adviced to be involed in the IDD survey indicators.

PMID- 24024369
TI  - [Effects of transtheoretical model intervention on improving self-esteem of obese
      children].
AB  - OBJECTIVE: To explore the effects of transtheoretical model (TTM) intervention on
      improving self-esteem status of obese children. METHODS: A quasi-experimental
      research was conducted using a repeated-measure, pretest-posttest control group
      design in one randomly-selected boarding school of Changsha, Hunan Province in
      China. Seventy-three obesity students (54 males, 19 females) among grade three to
      six were included. All participants received first assessment, including:
      demographic data, stage of change questionnaire, and the Self-Esteem Scale (SES).
      According to the baseline data, different intervention measures based on TTM were
      given to different students to promote them to begin exercise and improve their
      self-esteem status. Follow-up assessments were collected respectively at 1- and 6
      month after intervention. Intervention effects on proportion of obese children
      and self-esteem status as well as BMI were explored. All analyses were conducted
      using SPSS 17.0. RESULTS: After intervention, the proportion of obese children in
      precontemplation and maintenance stages was significantly different (P < 0.001).
      BMI and SES scores didn't change significantly. SES score was significantly
      different in five stages among three intervention points (P < 0.001). CONCLUSION:
      Obesity children who are in the later stages have higher self-esteem scores than
      those in former stages. Intervention based on TTM can help obese children move
      through the stages of change.

PMID- 24024370
TI  - [Objective assessment of school-time physical activity of a grade 1-2 junior
      school students in Beijing].
AB  - OBJECTIVE: To quantify the physical activity (PA) level during school time,
      especially in PE class, among Beijing junior school students. METHODS: 81 healthy
      adolescents (37 boys and 44 girls) aged 11-15 were recruited from grade 1-2 of a
      junior school, and a hip-worn ActiGraph GT3X + accelerometer was used to measure
      students' PA. Accelerometer-determined steps, moderate-and vigorous-intensity PA
      (MVPA), vigorous-intensity PA (VPA) and MET-mins at school time and physical
      education (PE) class were assessed. RESULTS: During school time, girls spent
      (47.2 +/- 16.0) mins performing, and boys (67.3 +/- 20.5) mins per day (P <
      0.01). Boys also had more steps per day, VPA time and MVPA MET-min than girls (P
      < 0.001). In PE class, boys spent 53.6% +/- 10.2% of time in MVPA, as compared to
      girls' 35.2% +/- 7.2%. Boys with normal BMI had the highest VPA time during PE
      than other groups (P < 0.05). No significant BMI group differences in PA level
      were found in girls. CONCLUSION: PA in school time was objectively qualified in
      Beijing junior school students. Girls were less active than boys. PE class
      provided a major portion of the VPA time and MVPA MET-min in school time PA for
      boys and girls. Boys with normal BMI had the highest PA level during PE classes.

PMID- 24024371
TI  - [Effects of different feeding practices at 0-6 months and living economic
      conditions on anemia prevalence of infants and young children].
AB  - OBJECTIVE: In order to understand the anemic prevalence in the infants and young
      children and its relation to the feeding pattern at 0-6 months and on economic
      income. METHODS: A questionnaire survey were used to collect the information on
      nutritional and health status of infants and young children (6 to 23 months)
      living in poverty-rural areas of Gansu Province, and hemoglobin concentration was
      measured. RESULTS: The prevalence of anemia was 58.2% in the children aged from 6
      months to 23 months. The rate of anemia in boys was higher than that of the girls
      (61.0% and 55.1%), but there was no significant difference. There were
      significant differences in hemoglobin levels among different age groups (F =
      5.206, P < 0.01). The child's hemoglobin concentration was trend to significantly
      decrease from 6-month-old and more, and reach to the lowest level at 12 months of
      age and more. After that, the hemoglobin began to gradually increase with age.
      The change of hemoglobin concentration was consistent with anemic prevalence, the
      higher prevalence of anemia was the group aged 6-month-old and more, and the
      group aged 12-month-old and more had highest prevalence. There were significant
      difference among the different feeding pattern on the anemic prevalence (chi2 =
      9.245, P < 0.05), and the prevalence of anemia in children fed with infant
      formula had the lowest anemic rate and was significantly lower than those of the
      mixed feeding and breastfeeding children (chi2 = 8.529 and 7.173, P < 0.05). The
      living economic conditions were a linear trend with the hemoglobin level of
      children, but there was no significant difference among the different feeding
      groups (F = 0.637, P > 0.05). The better household economic conditions, tends to
      have the lower in anemic prevalence, but there was no significant difference
      (chi2 = 1.666, P > 0.05). CONCLUSION: The children had lowest hemoglobin level
      and highest anemic prevalence in the group aged 12-month-old and more, the anemic
      prevalence of children fed with infant formula had significantly lower than those
      of the mixed feeding and breastfeeding children, and family economic status on
      the prevalence of anemia was not obvious. The present results showed that we
      should focus on the prevention and improvement of iron status and anemia in
      infants more than 6-months and young children.

PMID- 24024372
TI  - [Nutrition label reading and its influence factors research in five cities].
AB  - OBJECTIVE: To study reading status of nutrition label of residents in Beijing,
      Shanghai, Chongqing, Shenzhen and Jinan, and to analyze factors associated with
      nutrition label reading. METHODS: Two communities were chosed in each city. 200
      residents in every community were surveyed by trained doctors and 1993 residents
      were surveryed totally. The SPSS 16.0 statistical software was used for data
      analysis. RESULTS: Residents reading nutrition label accounted for 40.54%. The
      results of multi-variate Logistic regression showed that following factors were
      significant associated with the effect (P < 0.05), sex, age, nutrition-related
      knowledge, family number, attitude to nutrition knowledge, understanding of
      nutrition label, health, frequency of shopping and focus on food. CONCLUSION: The
      level of reading of nutrition label of the residents is low. It is necessary to
      implement nutrition and health education aimed at promoting residents' knowledge
      and reading of food nutrition labeling.

PMID- 24024373
TI  - [Relationship of the elderly nutrition knowledge and their education level in
      Nanjing].
AB  - OBJECTIVE: To study the relationship of the elderly nutrition knowledge, eating
      behavior and BMI status with their education level. METHODS: A questionnaire was
      designed to investigate 1367 elders in 26 nursing homes and communities of
      Nanjing. RESULTS: Accoording to the education lever, elders nutrition knowledge
      in college and high school was more than that in middle and primary school,
      significantly (P < 0.05, P < 0.01). Elders in college and high school groups
      could obtain much more informations via diversification, such as book, journal or
      magazine, interpersonal communication and TV or radio. While, 50% elders in lower
      education groups (middle and primary school) usually watch TV or lisen to the
      radio get knowledge. The higher education level, the higher income for elders.
      For this reason, their dietary structure and eating behavior were tending to be
      reasonable. Compared with the education lever, age and BMI, the effect of age on
      BMI was more than education lever. The ratio of weight loss and obesity in 75
      years old was clearly increased, their nutrition supplment needs more care.
      CONCLUSION: elderly education lever was a key factor on their nutrition knowledge
      and eating behavior (P = 0.00). In college and high school groups, elders
      nutrition knowledge and income were better than lower education level. However,
      the age was closed relative to BMI. When elders was over 75 years old, their body
      weight tend to loss or over and need more nutritional attention.

PMID- 24024374
TI  - [Survey of aflatoxins contamination of foodstuffs and edible oil in Shenzhen].
AB  - OBJECTIVE: To identify the aflatoxins contamination of foodstuffs and edible oil
      sold in Shenzhen. METHODS: As research subjects stratified random sampling of 238
      foodstuffs and edible oil, and applied with immuno-affinity column clean-up plus
      UPLC to determine the content of aflatoxin B1, B2, G1, and G2. RESULTS: Positive
      ratio of aflatoxin in rice, rice products, wheat flour, corn flour, edible oil
      were 35.3%, 33.8%, 13.9%, 46.7% and 24.5%,respectively. There were statistical
      differences between the positive ratio of aflatoxin in stereotypes packaged rice
      (26.5%) and bulk rice (56.3%) (chi2 = 11.6, P < 0.05). There were statistical
      differences between the positive ratio of aflatoxin in the rice produced in the
      area north of the Yangtze River (27.3%) and in the rice (41.4%) produced in the
      area south of the Yangtze River (chi2 = 7.257, P < 0.05). Aflatoxin B1 and B2
      were detected in rice products, wheat flour, corn flour. Positive ratio of
      aflatoxin B1, B2, G1, and G2 were 24.5%, 24.5%, 11.3% and 3.8% in the edible
      oil,respectively. The over standard rate of aflatoxin B1 was 5.66%, excessive
      samples were producted bulk and self-pressed peanut oil from unlicensed workshop.
      CONCLUSION: All the four kinds of aflatoxin were detected, while subtype B1 and
      B2 dominated aflatoxin contamination in the rice and edible oil samples. There
      are differences between in the northern and southern rice, and the same as in the
      stereotypes packaged and bulk rice sold at Shenzhen.

PMID- 24024375
TI  - [Biochemical and serological characterization Salmonella from retail meats in
      Guangdong Province].
AB  - OBJECTIVE: Salmonella isolates from meat in Guangdong Province were characterized
      to determine their phenotype and serotype, to investigate contamination status of
      meats by Salmonella and provide scientific basis for detection and further
      control. METHODS: 209 meat samples were detected according to methods GB 4789.4-
      2010 National food safety standard Food microbiological examination: Salmonella.
      The API 20E system was used to identify isolates. Serotyping of Salmonella
      isolates was performed by slide agglutination method using antisera to
      Salmonella. RESULTS: According to the detection results of 209 meat samples,
      forty-six Salmonella strains were isolated from 42 meat samples, the positive
      rate was 20. 10%. The majority of positive samples were fresh meat, 69.23% in
      duck, 37.14% in chicken, 20.00% in beef and 16.67% in pock. The strains
      identified as Salmonella by the API 20E were distributed in 7 profile numbers
      with two of them being predominant (6704752 and 6704552). The most common
      serotypes were Derby (21.74%), Typhimurium (10.87%), Enteritidis (8.70%),
      Tshiongwe (8.70%), Indiana (8.70%), Weltevreden (8.70%). CONCLUSION: Salmonella
      present in retail meats were common and phenotypically diverse in Guangdong
      Province.

PMID- 24024376
TI  - [Study on the serotype, virulence genes and pulsed field gel electrophoresis
      molecular typing of Vibrio parahaemolyticus isolated from clinical patients].
AB  - OBJECTIVE: To investigate the serotype virulence genes and molecular typing
      characteristics of Vibrio Parahaemolyticus isolated from diarrhea samples among
      2007 -2012. METHODS: The serotype was detected by using serological agglutination
      test. Thermo-stable direct hemolysin (tdh) and tdh-related hemolysin (trh) were
      detected by using real time PCR methods. 56 strains 03:K6 were analyzed for
      molecular typing by pulsed field gel electrophoresis(PFGE). RESULTS: (1) There
      are 14 serotypes, including 03: K6 (114,67.9%),04: K8 (25,14.9%), 03: K29
      (6,3.6%) and et al. Compared with the serotypes of strains from food poison,
      these from sporadic cases with diarrhea were different, but the main serotype was
      also 03:K6. (2) There are 4 types of virulence genes, including tdh+ trh- (161,
      95.8%), tdh+ trh+ (3,1.8%), tdh- trh+ (1, 0.6%) tdh- trh- (3, 1.8%). Compared
      with the virulence genes of strains from food poison, these from sporadic cases
      with diarrhea were different, but the main virulence gene was also tdh+ trh-.
      3,56 strains belonged to 15 PFGE strips and the similar degree is higher than
      86%. 10 patterns (P1-P4, P6, P7, P9, P10, P12, P15) had at lest two strains.
      CONCLUSION: The most V. Parahaemolyticus isolated from clinical patients was 03:
      K6 and tdh+ trh-. PFGE strips of V. Parahaemolyticus of 03: K6 from clinical
      patients exhibited a high degree of similarity, and correlation was found among
      strains.

PMID- 24024377
TI  - [Estimation of cadmium exposure level for the residents in metal contaminative
      area].
AB  - OBJECTIVE: To investigate situation of environmental cadmium pollution and
      exposure level of cadmium in general population. METHODS: Local self-seeded grain
      and vegetable sample were collected and detected for cadmium content. Dietary
      survey was carried out in the local resident at the same time. RESULTS: 833
      samples and 124 samples were collected respectively from polluted area and
      control area. Three days diet survey were conducted in 546 residents. Cd contents
      of grains from polluted area are higher than that from control area. corn, rape,
      potato and kidney bean (dry) are the main food. Rape is the major source of
      dietary cadmium intake. Average daily Cd intake and cumulative Cd intake of
      residents in polluted area exceeded the limitation of the cadmium from food
      recommended by WHO, while control area is under the limit. CONCLUSION: Self
      seeded vegetable is the main media of cadmium intake for the local resident in
      cadmium contaminated area, cumulative Cd intake for male > or = 55 years old and
      for female > or = 65 years old had reached 2000mg, which is the threshold for
      health hazard recommended by WHO.

PMID- 24024378
TI  - [Resilience status and impact factors in rural middle school students in Three
      Gorges areas].
AB  - OBJECTIVE: To assess the reliability and validity of the scale RYDM, as well as
      the resilience status and its impact factors. METHODS: 964 students were
      investigated. The participants were chosen through the stratified cluster
      sampling. The software of SPSS 17.0 was used for the analysis. RESULTS: (1) RYDM:
      The Cronbach alpha coefficient of the RYDM was 0.945. The split-half reliability
      was 0.865. The re-test reliability was 0.838. The correlations between total
      scale and 2 factor scales were 0.896 and 0.9743 respectively. The correlation
      between the 2 factor scales was 0.776. (2) The scores on family closeness, family
      high expectations, community expectation of left-behind children were lower than
      that of the no-left-behind children (P < 0.05). The protective factors of mental
      resilience in left-behind children were age, frequency of conflict with the
      guardian, worry degree about out-working parent(s) (P < 0.05). CONCLUSION:
      Reliability and validity of the RYDM scale are psychometrically qualified. The
      resilience of the left-behind children is worse in some aspects than that of the
      no-left-behind children, which is influenced most by family factors.

PMID- 24024379
TI  - [Study on the prevalence of depressive symptom and the association of parental
      occupational status with depression among high school students in Nanjing].
AB  - OBJECTIVE: To learn the prevalence of depressive symptom and to analyze the
      relationship between parental occupational status and depression among high
      school students in Nanjing. METHODS: With a stratified cluster random sampling
      method, the baseline survey was conducted in 2202 high school students chosen 53
      classes from 5 schools (3 junior high schools and 2 senior high schools) in
      baixia district chosen from 6 urban districts in 2009. The same samples were
      followed up in 2010 and 2011. Depressive symptoms were assessed using Zung Self
      rating Depression Scale (SDS). Parental occupational status was categorized into
      four groups, both employed, father unemployed, mother unemployed, and both
      unemployed. The total number of respondents was of 2160 in the baseline survey,
      with a response rate of 98.1%, in which 2118 (98.1%) and 2032 (94.1%) were
      followed up in 2010 and 2011, respectively. RESULTS: There was no significant
      difference in the positive rate of depressive symptom in the baseline and
      consecutive 2-year follow-up surveys (P = 0.108), while the proportions of
      moderate and severe depression were most highest in 2011 (P = 0.002). SDS index
      score and the positive rate of depression were most highest in students with
      parents both unemployed. Multivariate logistic analysis indicated that parental
      occupational status was significantly linked to depressive symptoms among
      students. The regression coefficients of generalized estimating equation (GEE)
      were statistically significant between parental occupational status and
      depression. CONCLUSION: Depressive symptoms is a common in high school student in
      Nanjing. Parental occupational status may be associated to depressive symptoms
      and much attention should be paid by health officers and instructive staff.

PMID- 24024380
TI  - [Interference of vitamin E on the brain tissue damage by electromagnetic
      radiation of cell phone in pregnant and fetal rats].
AB  - OBJECTIVE: To investigate the interlerence ot vitamin E on brain tissue damage by
      electromagnetic radiation of cell phone in pregnant and fetal rats. METHODS: 40
      pregnant rats were randomly divided into five groups (positive control, negative
      control, low, middle and high dosage of vitamin E groups). The low, middle and
      high dosage of vitamin E groups were supplemented with 5, 15 and 30 mg/ml vitamin
      E respectively since the first day of pregnancy. And the negative control group
      and the positive control group were given peanut oil without vitamin E. All
      groups except for the negative control group were exposed to 900MHz intensity of
      cell phone radiation for one hour each time, three times per day for 21 days.
      After accouchement, the right hippocampus tissue of fetal rats in each group was
      taken and observed under electron microscope. The vitality of superoxide
      dismutase (SOD) and glutathione peroxidase (GSH-Px), and the content of
      malondialdehyde (MDA) in pregnant and fetal rats' brain tissue were tested.
      RESULTS: Compared with the negative control group, the chondriosomes in neuron
      and neuroglia of brain tissues was swelling, mild edema was found around the
      capillary, chromatin was concentrated and collected, and bubbles were formed in
      vascular endothelial cells (VEC) in the positive fetal rat control group, whereas
      the above phenomenon was un-conspicuous in the middle and high dosage of vitamin
      E groups. We can see uniform chromatin, abundant mitochondrion, rough endoplasmic
      reticulum and free ribosomes in the high dosage group. The apoptosis has not fond
      in all groups'sections. In the antioxidase activity analysis, compared with the
      negative control group, the vitality of SOD and GSH-Px significantly decreased
      and the content of MDA significantly increased both in the pregnant and fetal
      rats positive control group (P < 0.05). In fetal rats, the vitality of SOD and
      GSH-Px significantly increased in the brain tissues of all three different
      vitamin E dosages groups when compared with the positive control group, and the
      content of MDA was found significantly decreased in both middle and high dosage
      of vitamin E groups(P < 0.05). The same results have also been found in high
      dosage pregnant rat group, but in middle dosage group only SOD activity was found
      increased with significance (P < 0.05). With the dosage increase of vitamin E,
      the vitality of SOD and GSH-Px was increasing and the content of MDA was
      decreasing. CONCLUSION: Under the experimental dosage, vitamin E has certain
      interference on damage of antioxidant capacity and energy metabolization induced
      by electromagnetic radiation of cell phone in pregnant rats and fetal rats.

PMID- 24024381
TI  - [Effects of different zinc nutritional status on iron metabolism in rats].
AB  - OBJECTIVE: To study the effects of different zinc nutritional status on iron
      metabolism and explore the potential role of iron regulator protein 2 (IRP2)
      under conditions of zinc deficiency. METHODS: Forty clean male SD rats were
      randomly divided into four groups according to the weight and every group
      included 10 rats. The rats were administrated normal iron and zinc control group
      (ZA group), normal iron and slight deficient group (ZD group), Paired fed group
      (PF group), normal iron and zinc excessive group (ZE group). Rats were sacrificed
      by sodium pentobarbital anesthesia after 8 weeks and serum, liver and spleen of
      the rats were collected. The serum zinc, serum iron, hemoglobin, serum
      transferrin receptor, serum ferritin, iron and zinc in the liver, iron and zinc
      in the spleen were determined. The level of IRP2 mRNA expression,liver
      transferring receptor (TfR) mRNA expression and ferritin (Fn) mRNA expression
      were measured using reverse transcription polymerase chain reaction (RT-PCR)
      method. RESULTS: Compared with that of the control group, iron content both in
      the liver and spleen, and the concentration of serum iron in ZE group was
      significantly decreased (P < 0.05). Compared with the control group, zinc
      deficiency increased iron content in the liver and the concentration of serum
      transferrin receptor significantly (P < 0.05), while the concentration of serum
      iron was significantly decreased (P < 0.05). Compared with the control group,
      zinc deficiency increased the level of IRP2 mRNA and TfR mRNA expression in the
      liver significantly (P < 0.05). CONCLUSION: Zinc may affect iron nutritional
      status by influencing absorption, storage and transportation of iron. Zinc
      deficiency influences iron homeostasis in cells through affecting the expression
      of IRP2 and the activity of IRP-RNA combination and then change the expressions
      of ferritin and transferrin mRNA.

PMID- 24024382
TI  - [Effects of copper deficiency on iron metabolism in rats].
AB  - OBJECTIVE: To study the effects of copper deficiency on iron metabolism, the
      expression of IRP mRNA and Fn mRNA and transferrin receptor mRNA in rats.
      METHODS: Forty clean male SD rats were randomly divided into four groups
      according to body weight and there were 10 rats in each group. The groups are
      normal iron and copper control group (group I), copper deficiency group (group
      II), normal iron and copper slightly deficient group (group III), both iron and
      copper slightly deficient group (group IV). After 8 weeks, all the rats were
      killed by sodium pentobarbital anesthesia and all samples were collected and
      detected for gene expression. RESULTS: Compared with the controls, the contents
      of serum iron and serum ferritin in completely copper deficiency group decreased
      (P < 0.05), but the level of serum transferrin receptor increased significantly
      under the complete copper deficiency (P < 0.05). Compared with that of the
      control group, the level of IRP2 mRNA in complete copper deficiency group was
      significantly increased (P < 0.05), and the level of transferrin receptor mRNA
      was also increased compared with that of the control group,compared with the
      control group the level of ferrintin RNA in complete copper deficiency group was
      significantly decreased (P < 0.05). CONCLUSION: The nutritional status of the
      iron may be affected by copper deficiency through influencing the absorption, the
      results indicate that copper deficiency influences iron homeostasis in cells
      through affecting the expression of IRP2 and the activity of IRP-RNA combination
      which change the expressions of ferritin and transferrin mRNA.

PMID- 24024383
TI  - [Development of Clostridium perfringens selective chromogenic medium].
AB  - OBJECTIVE: To screen the Clostridium perfringens selective composition to develop
      a Clostridium perfringens selective chromogenic media. METHODS: To evaluate the
      role in promoting the growth of the target bacteria of growth factor such as
      mannitol, sodium pyruvate, and magnesium sulfate. Comparing the inhibition of
      antibiotics such as cycloserine, neomycin, polymyxin and sulfadiazine of target
      bacteria and non-target bacteria. To compare the reaction of chromogenic
      substrates such as BCIP, PNPP, X-Gal, Mu-Gal and ONPG. Screening the best
      enzymatic factors among magnesium sulfate, calcium sulfate, manganese sulfate,
      zinc sulfate. Then to determine the optimal dose. To determine the ultimate
      composition of chromogenic media. RESULTS: Ultimately determines the composition
      of media, sodium pyruvate 200 mg, cycloserine 0.5 mg, BCIP 6 mg, Mu-Gal 6 mg,
      magnesium sulfate 72 mg. Add all the composition into 100 mL nutritional broth
      medium to prepare the medium. Clostridium perfringens growth in chromogenic
      medium, TSC medium and SPS medium have no significant difference. CONCLUSION:
      Clostridium perfringens selective chromogenic medium can be used in detection of
      Clostridium perfringens.

PMID- 24024384
TI  - [Detection of Salmonella, Shigella and Staphylococcus aureus based on quantum
      dots and immunomagnetic beads].
AB  - OBJECTIVE: To establish a detecting method of Salmonella, Shigella and
      Staphylococcus aureus by using quantum dots and immunomagnetic beads. METHODS:
      The polychrome colour CdSe quantum dots were synthetized by water phase process.
      Triad colour quantum dots were conjugated with specific anti-Salmonella, anti
      Shigella and anti-Staphylococcus aureus antibody by covalent cross-linking
      reaction, and then the coupled product was confirmed by SDS-PAGE and ultraviolet
      absorption spectrum. Using immunomagnetic enrichment and quantum dots labeling
      specific antibody, the fluorescence intensity of Salmonella, Shigella and
      Staphylococcus aureus were observed by fluorescence microscope. RESULTS: The
      coupled reaction was successful by SDS-PAGE and ultraviolet absorption spectrum.
      Using immunomagnetic enrichment and quantum dots with different color and
      different wavelength labeling specific antibody, the detection time was less than
      2h in the same reaction system. The samples infection with target bacteria were
      detected directly. The detection limit was 10 CFU/ml. CONCLUSION: This method can
      detect Salmonella, Shigella and Staphylococcus aureus quickly and specificly.

PMID- 24024385
TI  - [Effects on DNA damage and apoptosis and P53 protein expression induced by phoxim
      in rat bone marrow stem cells].
AB  - OBJECTIVE: To study the DNA damage and oxidative damage and apoptosis and P53
      protein expression in rat bone marrow stem cells cultured in vitro induced by
      phoxim. METHODS: Rat bone marrow stem cells of P3 cultured in vitro were treated
      with phoxim of different concentrations (0, 0.2, 2 and 20 microg/L) for 24 h
      after 48 h cultured. The total activity of SOD, CAT and MDA content, survival
      rate in cell were detected by spectrophotometry,and the DNA damage were detected
      by single cell gel electrophoresis. The cell apoptosis were detected by flow
      cytometry,and the P53 protein expression were detected by Western blot. RESULTS:
      With the 0.2 and 20 microg/L of phoxim concentrations treated for 24 h in culture
      media, the total activity of SOD and CAT were significantly decreased compared
      with the controls (P < 0.05). With the increase of phoxim concentration in
      culture media, the MDA contents, DNA damage, apoptosis rates and P53 protein
      expression of rat bone marrow stem cells was increased significantly compared
      with the controls (P < 0.05). CONCLUSION: Phoxim can increase the rates of DNA
      damage, oxidative damage and induce apoptosis and expression of P53 in rat bone
      marrow stem cells, and there exists a rise tendency with the increase
      concentration of phoxim.

PMID- 24024386
TI  - [Prevalence of HIV among men who have sex with men of inland high school and
      college students in China: a meta-analysis].
AB  - OBJECTIVE: To analyze the prevalence of HIV among men who have sex with men (MSM)
      of inland high school and college students in China, and to analyze the
      differences between sample size, sampling methods and study period. METHODS:
      Electronic search strategy was carried out, using WanFang database, China Journal
      Full-text database, VIP database, CBM and PubMed database to collect data on high
      school and college students, HIV and MSM, among residents in China. Fixed effects
      model or random effects model was employed according to statistical tests for
      homogeneity. Publication bias was assessed by funnel plot. RESULTS: Ten studies
      were selected with a total of 2014 students-MSM and 106 HIV infected. The overall
      prevalence of HIV was 4.6% (95% CI 2.9%-6.3%). The prevalence of HIV was
      stratified by factors as sample size, sampling methods and study period of the
      study. The pooled prevalence rates of HIV were as follows: 4.7% (95% CI 2.5%
      7.0%) and 4.7% (95% CI 1.9%-7.4%) for sample size > 200 and sample size 200, 6.1%
      (95% CI 3.0%-9.1%) and 2.9% (95% CI 1.7%-4.1%) for snow sampling and non-snow
      sampling, respectively. The pooled prevalence of HIV were 3.0% (95% CI 1.7%-4.2%)
      in the study year of 2005-2007 and 6.0% (95% CI 3.1%-9.0%) in 2008-2010,
      respectively. The pooled prevalence of HIV was higher in snow sampling than non
      snow sampling, in the study year of in 2008-2010 than in 2005-2007. CONCLUSION:
      The prevalence of HIV among MSM of inland high school and college students in
      China was higher than general population.

PMID- 24024388
TI  - [Overload of emergencies: if we change the paradigm?].

PMID- 24024387
TI  - [Meta-analysis of the association between adiponectin gene +276g/T polymorphisms
      and coronary atherosclerotic heart disease].
AB  - OBJECTIVE: systemically evaluate the association between +276G/T single
      nucleotide polymorphisms of adiponectin gene and coronary atherosclerotic heart
      disease in Chinese population. METHODS: 8 case-control studies about +276G/T
      polymorphism that were based on our inclusion criterion and available in the
      literature were reviewed. Meta analysis was carried out by Review Manager 4.2
      software. RESULTS: Results from Metaanalysis demonstrated no significant
      heterogeneity among the studies about +276G/T polymorphisms and showed
      significant association between the +276G/T polymorphism and coronary disease in
      the Chinese population, and the fixed effects OR of the allele +276G to
      susceptibility of the disease was (OR = 1.93, 95% CI 1.32-2.82, P = 0.0007).
      CONCLUSION: The current paper on Meta-analysis demonstrated a correlation between
      the +276G/T single nucleotide polymorphism and the cononary disease in Chinese
      population.

PMID- 24024390
TI  - [Management of the drunken patient].
AB  - Acute ethanol intoxication is frequent in emergency departments. The clinical
      presentation is highly variable and ranges from an inebriety to a coma and
      sometimes an agitated patient. You have to examine completely the patient and to
      do complementary exams with a capillary glycemia as the minimal standard. We must
      keep in mind that an acute ethanol intoxication is a diagnosis of exclusion. With
      trauma patients, we have to keep a low threshold for asking radiological advanced
      imaging, like cerebro-cervical CT scan. The patient should be reexamined
      frequently. The treatment is a supportive one. If the patient is agitated, you
      can give him haloperidol or a benzodiazepine. Before discharge, the patient
      should see the alcohologic team.

PMID- 24024389
TI  - [Recreational drugs: the complication's pleasure?].
AB  - Steadily increasing since 1990, the use of psychoactive substances was expanded
      to new designer drugs (bath salts, spice) with so original still unknown
      pharmacological effects. At the beginning, the pleasure, first feeling, turns
      sometimes, in acute medical emergency and then, in some cases, in chronic
      diseases. Side expected or not desired effects, seen in emergency departments
      could be necrotizing gangrene among consumers Krokodil or dystonic reactions in
      consumers of Spice. Moreover, adulterants could increase the dangerosity of the
      substances. Searching a toxidrome helps to find the incrimining substance.

PMID- 24024391
TI  - [Mushroom poisoning].
AB  - Mushroom poisoning is a regular complaint for consultation in emergency
      facilities. These situations are usually benign and symptomatic treatment is
      sufficient. However, severe damage can occur, potentially life-threatening. We
      review the various syndromes associated with the toxins involved, their
      management and the major signs that are suggestive of serious injury and
      requiring hospitalization.

PMID- 24024392
TI  - [Toxicity of metformin, pro- or con- a future restriction to its
      contraindications?].
AB  - Type 2 diabetes, a world-wide epidemic, is a major concern of health systems
      around the world. The recommandation of its early management with metformin by
      the majority of guidelines has made metformin the object of multiple studies to
      demonstrate its benefits, but more importantly its side effects among whom the
      most serious is lactic acidosis. The latter is rare, but responsible for high
      mortality rates and is strongly associated with acute and chronic conditions for
      which diabetics are prone. These conditions reduce tissue perfusion and activate
      anaerobic metabolism producing lactate. Despite the beneficial effects of
      metformin and the debate about its causal role, we should remain vigilant about
      this serious complication by respecting its usage's contraindications, for the
      time being unchanged.

PMID- 24024393
TI  - [Paracetamol overdose].
AB  - Acetaminophen is the most widely used analgesic-antipyretic and is available as
      an over-the-counter medication in many countries. Although generally safe at
      usual therapeutic doses, acetaminophen may cause hepatic toxicity in case of
      chronic or acute overuse and even at therapeutic doses in susceptible
      individuals. The aim of this article is to review the mechanisms of acetaminophen
      toxicity and to review the critical steps in the management of acute or chronic
      acetaminophen intoxication.

PMID- 24024394
TI  - [Fruits and vegetables: can they be dangerous?].
AB  - Fruits, vegetables and spices are found in our everyday food consumption.
      However, some contain potentially toxic substances, particularly when consumed in
      large amounts. These risks may be greater for certain susceptible individuals and
      may depend on how the ingredients are prepared. Food poisoning is generally
      speaking self-limiting, but may be life threatening. This article discusses the
      possible toxic effects of certain common foodstuffs, as described in the current
      medical literature.

PMID- 24024395
TI  - [The new vaccine challenges of "humanization" of HIV].

PMID- 24024397
TI  - [Suicide provoked: the irreversible is in motion to Benelux].

PMID- 24024398
TI  - [Doping: there is an urgency to dare to look in the mirror].

PMID- 24024399
TI  - [The witnesses].

PMID- 24024400
TI  - [Broadening the horizons].

PMID- 24024401
TI  - [Nursing on the "Africa Mercy": on the ship of hope and healing].

PMID- 24024402
TI  - [Interview with Evelyne Boillat, nurse on the Mercy ship: "One receives twice as
      much in return"].

PMID- 24024403
TI  - [Lung transplant patients of the pneumology department: every breath counts].

PMID- 24024404
TI  - [ICN congress in Melbourne: breaking the vicious cycle of poverty].

PMID- 24024405
TI  - [Properly positioning nursing care].

PMID- 24024406
TI  - [FaGe transfer quota: the campaign for talented personnel].

PMID- 24024407
TI  - [Micro-educational concept: self catheterization, a challenge for life].

PMID- 24024408
TI  - ["Ethics and nursing practice" document: suggestion for ethical reflection].

PMID- 24024409
TI  - [Sonja Morgenegg-Marti: "I directly approach persons" (interview by Urs Luti)].

PMID- 24024410
TI  - [Quite a difference!].

PMID- 24024411
TI  - [35th assembly of delegates: impact for nursing care].

PMID- 24024412
TI  - [10 candles for PDSB in Switzerland: a method that has been proven].

PMID- 24024413
TI  - [The death of Alba Viotto: a life dedicated to defending the weakest].

PMID- 24024414
TI  - [CII 2013 Congress in Melbourn: nurses in a campaign against poverty].

PMID- 24024415
TI  - [A method inspired by acupuncture].

PMID- 24024416
TI  - [Dreams are wishes...].

PMID- 24024417
TI  - [Integrating evidence-based medicine and personalized medicine].

PMID- 24024418
TI  - [Crohn's disease and MRI: assessment of inflammatory activity and tissue damage].
AB  - Crohn's disease is an inflammatory bowel disease that affects mainly young people
      and includes periods of remission interspersed with occasional flare-ups. Entero
      MR (Magnetic Resonance) is a non-radiating and a non-invasive tomography imaging
      technique. Entero-MR has recently proven its ability to assess inflammatory
      activity and structural damage of the bowel in Crohn's disease which are
      fundamental elements in the therapy planning. These considerations explain why
      entero-MR is playing an increasing role in the evaluation of Crohn's disease.

PMID- 24024419
TI  - [The management of systemic lupus erythematosus with biological therapies].
AB  - The efficacy and safety of targeted biological therapies have been analyzed in
      patients suffering from systemic lupus erythematosus. In renal lupus, infliximab
      has shown prolonged improvement of the renal function after the induction period
      (small open studies), whereas abatacept had no significant efficacy (randomised
      controlled study). In renal and non renal lupus, rituximab did not confirm its
      efficacy in two randomised controlled studies. In non renal lupus, epratuzumab
      has shown efficacy in a phase IIb. Belimumab at the high posology of 10 mg/kg has
      also shown significant efficacy in two large randomised controlled studies.

PMID- 24024420
TI  - [Chronic myelomonocytic leukemia: from diagnosis to treatment].
AB  - Chronic myelomonocytic leukemia (CMML) is a disease typically of the elderly. It
      is suspected when monocytosis reaches 1000/microl. It may be associated with "B"
      symptoms (fever, sweating, and weight loss) but also visceral, skin and
      autoimmune complications. Current treatment strategies aim at reducing the
      symptoms and have no curative goals. In this context hypomethylating agents have
      shown a good efficacy. Allogeneic hematopoietic stem cell transplantation (HSCT)
      remains the only curative option but remains difficult to perform in elderly
      patients population, even if transplantation with a reduced intensity
      conditioning has reduced the risks. A new prognostic scoring helps to recognize
      the patients with poor prognosis and to better selected candidates for the HSCT.

PMID- 24024421
TI  - [Primary mitral regurgitation: indications for surgery and recent advances].
AB  - Mitral regurgitation (MR) is, in Europe, the second most common valvular disease.
      Primary MR represents 61% of cases. The surgical indications for symptomatic
      patients with severe primary MR, are subject to a broad consensus with strong
      levels of recommendations. In asymptomatic patients, levels of recommendations
      are weaker despite the numerous publications. Exercise echocardiography has
      emerged as a useful tool for the management of the patients and appeared in the
      latest European recommendations. It continues to be the subject of numerous
      studies demonstrating its usefulness for risk stratification in asymptomatic
      patients. The next advances in this field will probably argue for an earlier
      surgery in these kinds of patients.

PMID- 24024422
TI  - [Management of prolactinoma].
AB  - The prevalence of pituitary adenoma is of 1/1000 and has been fora long time
      underestimated. Prolactinomas represent the most frequent subtype (60%). From the
      mid eighties, their treatment is usually simple and efficient, allowing clinical,
      biological and tumoral control in most cases. However, management of carcinoma or
      resistant prolactinoma can be challenging. In these particular cases, a
      multimodal therapy approach is needed. Recently, progress in genetics of
      pituitary adenoma has allowed a better understanding and management of these
      particular cases. In consequence, genetic evaluation is recommended in FIPA
      (Familial Isolated Pituitary Adenoma) cases and in young patients with
      macroprolactinomas.

PMID- 24024423
TI  - [Use of metformin in diabetic patients with cardiac disease: benefit-risk
      balance].
AB  - Metformin is unanimously considered as the first-line glucose-lowering agent in
      type 2 diabetes. Theoretically, however, it cannot be prescribed in a large
      proportion of patients because of the presence of numerous contraindications
      corresponding to situations that may increase the risk of lactic acidosis. Recent
      data suggest that type 2 diabetes patients who are considered as being "at risk"
      because of the presence of cardiac disease still take benefit from metformin
      therapy, with a reduction of morbidity and mortality compared with other glucose
      lowering agents. The present review analyzes the benefit-risk balance of
      metformin therapy in special populations, namely patients with stable coronary
      artery disease, acute coronary syndrome or myocardial infarction, or congestive
      heart failure.

PMID- 24024424
TI  - [Urinary incontinence: neither men nor women should be forgotten].
AB  - The prevalence of urinary incontinence is higher in women, but up to 40% of
      elderly men suffer from it. It is very important for care givers to search
      actively for this problem, because only half of the patients, mostly men, will
      seek help specifically for this symptom. The patients, who do not ask for help,
      mostly women, think that urinary incontinence is a normal problem while getting
      old and think that there is no specific treatment for it. Urinary incontinence
      has an important impact on physical and mental health and has a high economic
      cost. Men with urinary incontinence are less well taken in charge than women up
      to the use of absorbent pads, which they partly fix up themselves.

PMID- 24024425
TI  - [Acquired long QT syndrome].
AB  - The long QT syndrome may be acquired or genetically determined. The syndrome is
      characterized by a prolonged QT interval and is associated with an increased risk
      of cardiac arrhythmia such as a torsade de pointe and death. Electrolytes
      disorders such as hypomagnesemia and hypokaliemia and several drugs may increase
      the risk to develop a long QT syndrome. The epidemiology, the aetiology, the
      diagnostic approach as well as the management options of an acquired QT
      prolongation is discussed and reviewed herein.

PMID- 24024426
TI  - [Public health research projects by third year medical students].

PMID- 24024427
TI  - [Mental health disorders in Tessin: factors influencing a return to work].

PMID- 24024428
TI  - [Cystic fibrosis in the adult patient].

PMID- 24024429
TI  - [Shedding light on noma disease].

PMID- 24024430
TI  - [The care of those with medical insurance].

PMID- 24024431
TI  - [The death of Dr. Olivier Ameisen, promoter of baclofen for alcoholism].

PMID- 24024432
TI  - [Tomorrow our steaks will almost be alive].

PMID- 24024433
TI  - [Medical data, a new mythology].

PMID- 24024434
TI  - [Risk assessment and control measures for import of African schistosomiasis into
      China].
AB  - The habitats of Biomphalaria straminea, the intermediate host of Schistosoma
      mansoni, have been found in Hong Kong Special Administrative Region and Shenzhen
      City of People's Republic of China. Currently, there is a sharp increase in the
      number of Africa-aid projects and workers moving to Africa, and more and more
      cases infected with S. mansoni or S. haematobium returning from African countries
      have been detected in China. The possibility of transmission of African
      schistosomiasis in Chinese mainland, in the context of global climate warming,
      has received much attention. This paper illustrates the risk of transmission of
      African schistosomiasis in China based on biological and epidemiological
      features, and proposes interventions to tackle the risk.

PMID- 24024435
TI  - [Toxicity of 50% ethanol salt powder of niclosamide on growth of silkworms].
AB  - OBJECTIVE: To observe the toxity of niclosamide on the growth of silkworms.
      METHODS: Mulberry leaves were soaked in the different concentrations of solution
      of 50% ethanol salt powder of niclosamide for 10 s or 3 min, and then the leaves
      were fed to silkworms. The death rates of silkworms and the weight of cocoons
      were observed. Normal feeding control groups were established. RESULTS: The death
      rates were 22.5%-85.0% and 56.0%-100% in the 10-s-soaked groups and 3-min groups,
      respectively, which were significantly higher than those in the control groups.
      CONCLUSION: The 50% ethanol salt powder of niclosamide has a toxity for silkworm.
      Therefore, we should properly handle the relationship between the Oncomelania
      snail control and silkworm breeding.

PMID- 24024436
TI  - [Risk assessment of schistosomiasis transmission in earthquake-stricken areas
      after the Lushan Earthquake in Sichuan Province on April 20, 2013].
AB  - OBJECTIVE: To assess the impact of the "4 x 20" Lushan Earthquake on the risk of
      schistosomiasis transmission in Lushan and Tianquan counties, so as to provide
      the evidence for formulating appropriate measures for schistosomiasis prevention
      and control. METHODS: Based on a comprehensive literature review, an analysis of
      schistosomiasis monitoring data in the earthquake affected counties, and a field
      investigation, a rapid assessment on the impact of the earthquake on
      schistosomiasis was conducted. RESULTS: Lushan and Tianquan counties were two
      endemic areas of schistosomiasis with high transmission level in history,
      especially Lushan County where Oncomelania snail distribution/density was the
      highest in Sichuan Province. After the earthquake, the streams and damaged
      ditches were blocked up, potentially leading to the spread of Oncomelania snails,
      and the damaged sanitary facilities may also lead to the release of excrement,
      contaminating the environment where snails resided. Meanwhile, the people who
      were relocated due to the earthquake may have higher exposures to contaminated
      environment. In addition, increasing population mobility (e.g. relief workers)
      also had the potential to bring infection sources in the earthquake affected
      areas. Further, animals, which may serve as reservoirs for the parasite such as
      homeless dogs, may also add the complexity of local schistosomiasis transmission.
      CONCLUSIONS: The epidemic risk of schistosomiasis in Lushan and Tianquan counties
      is high. To prevent the outbreak and epidemic of schistosomiasis, the victim
      settlements should be established appropriately and the excrement should be
      managed carefully. Meanwhile, the snail control should be carried out in the high
      risk environments. The health education, monitoring, patient treatments and
      expanded chemotherapy should be carried out and strengthened.

PMID- 24024437
TI  - [Establishment and application of rapid assessment system of environment with
      high transmission risk of schistosomiasis in marshland and lake regions. I.
      Establishment of an index system with Delphi method].
AB  - OBJECTIVE: To establish an index system for rapid assessment of environment with
      high transmission risk of schistosomiasis in marshland and lake regions. METHODS:
      The alternative indices were established preliminarily by the documentary method,
      and then the Delphi method was used two rounds to select the indices and
      establish the index system. The degree of familiar and authority of the experts
      as well as the weights of all indices were assessed. RESULTS: A total of 3
      primary indices namely morbidity in domestic animals, morbidity in humans and
      Oncomelania snail status were established, among which the weight of morbidity in
      domestic animals (0.68) was the highest. Totally 16 secondary indices were
      established, among which the combinative weights of the positive rate of wild
      feces (0.09), the infection rate of livestock (0.09), the infection rate of
      humans (0.07), the number of cases with acute schistosomiasis (0.07), the area
      with infected snails (0.07), and the density of infected snails (0.07) were the
      highest. The coefficients of familiar degree and authority degree of the experts
      of the primary indices were 0.79-0.85 and 0.88-0.91, and those of the secondary
      indices were 0.68-0.86 and 0.77-0.91, respectively. CONCLUSIONS: The index system
      for rapid assessment of environment with high transmission risk of
      schistosomiasis in marshland and lake regions is established preliminarily. Using
      this system, we can assess the key endemic indices of humans, domestic animals
      and snails to understand the endemic situation in the investigated sites.

PMID- 24024438
TI  - [Bibliometric research on Chinese literatures published by five provincial
      institutes of schistosomiasis prevention and control in lake regions of China
      from 2002 to 2011].
AB  - OBJECTIVE: To evaluate the status of the Chinese literatures published by the 5
      institutes of schistosomiasis prevention and control in Hunan, Hubei, Jiangxi,
      Anhui, and Jiangsu provinces from 2002 to 2011. METHODS: All the Chinese
      literatures on schistosomiasis research published by the five provincial
      institutes of schistosomiasis prevention and control in lake regions of China
      from 2002 to 2011 were collected and analyzed by using the bibliometric software
      NoteExpress 2. Authors, journals, published date, and study affiliations were
      captured. RESULTS: The number of the published literatures from 2002 to 2011 was
      1 127 and the comprehensive influence index was 984.547 presenting an uptrend.
      Most of the papers were published in the Chinese Journal of Schistosomiasis
      Control accounting for 50.5%, and the core authors based on Zhou, Liang, and Hong
      were formed. Jiangsu Institute of Parasitic Diseases was the first in all the
      statistical indexes. However, there existed an unbalanced phenomenon among the
      five provinces in the total status, author's information and the comprehensive
      influence index. CONCLUSIONS: The number of the literatures increased steadily
      and the quality improved especially in Jiangsu Province. However, there exists an
      obvious imbalance in literature type distribution. The communication of
      scientific research is an urgent need in order to improve scientific research.

PMID- 24024439
TI  - [Study of closed colony of Microtus fortis infected with Schistosoma japonicum].
AB  - OBJECTIVE: To understand the pathological changes of tissues and organs in
      Microtus fortis infected with Schistosoma japonicum for further insight into the
      biological dynamic variation and explore immune mechanisms of M. fortis against
      S. japonicum infection. METHODS: The healthy M. fortis and mouse were infected
      with cercariae of S. japonicum through abdominal skin. On the day 12, 20 and 40,
      the M. fortis and mouse were sacrificed by cervical dislocation and dissected.
      The liver and kidney slices of M. fortis and mouse of the different groups were
      prepared and stained with hematoxylin eosin stain (HE) by conventional
      techniques, respectively. RESULTS: We did not find obvious lesions on the
      internal organs of mouse 12 d and 20 d after the infection and the lesions of M.
      fortis 40 d after the infection. However, white nodules appeared on the liver,
      kidney and spleen of the M. fortis 12 d and 20 d after the infection, and there
      were a lot of S. japonicum worms on pathological sections of inflamed liver and
      kidney tissues, and the boundary between worms and normal organization was clear.
      There were no parasites on pathological section of liver and kidney of mouse 12 d
      and 20 d after the infection. CONCLUSION: Among M. fortis, there are severe
      immune responses and the immune responses have an individual difference 12 days
      after S. japonicum infection.

PMID- 24024440
TI  - [Preliminary evaluation of promoter regions of four Schistosoma japonicum genes
      for expressing a luciferase reporter].
AB  - OBJECTIVE: To evaluate the relevant promoter regions of four Schistosoma
      japonicum genes for expressing a luciferase reporter. METHODS: The polymerase
      chain reaction (PCR) was used to amplify the promoter regions of four S.
      japonicum genes and then each PCR product was cloned into a pGlu-Basic vector
      according to the standard molecular procedures. These recombinant plasmids were
      either transfected into human HEK293 cells by using lipofectamine or introduced
      into cultured schistosomes by electroporation. Then, the luciferase activities
      were measured by using a dual luciferase reporter system in a luminometer.
      RESULTS: Each promoter region of four S. japonicum genes was obtained and the
      corresponding recombinant vector containing the promoter region was successfully
      constructed. The transfection of the recombinant plasmids into the human HEK293
      cells and cultured schistosomes resulted in a significant elevation of the
      luciferase reporter activity. CONCLUSIONS: The promoter regions of four S.
      japonicum genes are obtained and the luciferase reporter genes driven by the four
      promoter regions are preliminarily evaluated. The study provides a foundation for
      the usage of these promoters for genetic manipulation in S. japonicum.

PMID- 24024441
TI  - [Expression of vascular growth factors in intestinal tissues in colorectal
      carcinoma patients with schistosomiasis japonica].
AB  - OBJECTIVE: To investigate the differences of mRNA quantitation and protein
      expression of vascular growth factors including platelet-derived endothelial cell
      growth factor (PD-ECGF) and vascular endothelial growth factor (VEGF) in
      intestinal tissues in colorectal carcinoma patients with and without
      schistosomiasis. METHODS: Thirty colorectal carcinoma patients with
      schistosomiasis and 30 colorectal carcinoma patients without schistosomiasis were
      included in this study. The mRNA quantitation and protein expression of PD-ECGF
      and VEGF in the normal tissue, peri-carcinoma tissue as well as carcinoma tissue
      obtained from surgical specimens were detected by qRT-PCR and Western blot.
      RESULTS: The mRNA relative quantitations of PD-ECGF in normal tissue, peri
      carcinoma tissue and carcinoma tissue in the colorectal carcinoma patients with
      schistosomiasis were 1.726, 1.766 and 2.729 times to those in the colorectal
      carcinoma patients without schistosomiasis, respectively. The corresponding ones
      of VEGF were 2.138, 1.831 and 3.376 times, respectively. The protein expression
      levels of PD-ECGF and VEGF in normal tissue, peri-carcinoma tissue and carcinoma
      tissue were higher in the colorectal carcinoma patients with schistosomiasis than
      in the colorectal carcinoma patients without schistosomiasis. CONCLUSIONS: The
      expressions of vascular growth factors including PD-ECGF and VEGF are higher in
      the colorectal carcinoma patients with schistosomiasis than in the colorectal
      carcinoma patients without schistosomiasis. Therefore, schistosomiasis may be one
      of the risk factors of colorectal cancer.

PMID- 24024442
TI  - [Prevalence of IgG antibodies specific to Toxoplasma gondii among college student
      blood donors in Shijiazhuang City].
AB  - OBJECTIVE: To understand the epidemiological status of Toxoplasma gondii
      infection among blood donors in college students in Shijiazhuang City, China.
      METHODS: The blood samples were collected from the students in 4 universities and
      healthy adults in Shijiazhuang City, and the IgG antibodies specific to T. gondii
      were detected by using ELISA. RESULTS: The sera of 864 blood donors (422 males
      and 442 females) and 95 healthy adults were collected and checked for the IgG
      antibody titers against T. gondii. The positive rates of IgG antibody specific to
      T. gondii were 5.1% and 7.4% in college student blood donors and healthy adults,
      respectively (P < 0.05). The positive rates were not significantly different
      between the sexes (5.0% for the male and 5.2% for the female in blood donors of
      college students) and among the different universities (P > 0.05). CONCLUSION:
      For the higher positive rates of IgG antibody specific to T. gondii, it should be
      necessary to control T. gondii infection in blood donors in college students.

PMID- 24024443
TI  - [Mollusicidal effects of some species of plants in hilly and mountainous areas].
AB  - OBJECTIVE: To valuate the mollusicidal effects of some plants cultivated in the
      hilly and mountainous areas on Oncomelania hupensis and screen the plants against
      O. hupensis snails. METHODS: The mollusicidal effects of water extracts of plant
      materials were tested in laboratory. RESULT: The LC50 of all the species in 24 h,
      48 h, and 120 h reached the middle noxious level against O. hupensis snails.
      According to the taxis of LC50(s) in 120 h, Eucalyptus camaldulensis was best
      with a LC50 of 0.013%, and Ailanthus altissima, Zanthoxylum bungeanum, Juglans
      regia, Melia azedarach, Nerium indicum, Pterocarva stenobtera, Cinnamomum
      camphora, Vetiveria zizanioides, and Citrus reticulata were the second with LC50
      (s) between 0.020% and 0.370%, and Zingiber officinale had a lower effect on
      snail control with a LC50 of above 0.500%. There was a correlation between the
      death rate of snails and soak time. CONCLUSION: The resources of snail-restrained
      plants are very abundant, and four plants, such as Eucalyptus camaldulensis,
      Ailanthus altissima, Cinnamomum camphora, and Vetiveria zizanioides have some
      mollusicidal effect.

PMID- 24024444
TI  - [Epidemic situation and control strategy of imported malaria in Hubei Province
      from 2006 to 2011].
AB  - OBJECTIVE: To understand the characteristics of imported malaria in Hubei
      Province so as to provide the evidence for formulating the prevention and control
      strategy. METHODS: The data of all imported malaria cases from 2006-01 to 2011-07
      were retrospectively analyzed, and at the same time, the imported malaria cases
      since 2010 were interviewed through telephone and the cases since 2011-05 were
      interviewed face to face. All data were analyzed with EpiInfo. RESULTS: There
      were 195 imported malaria cases from 2006-01-01 to 2011-07-07, and there was a
      rising trend but there was no obvious difference among seasons. The interval
      between the disease onset and diagnosis was shorter in high educated people than
      low educated people (chi2 = 10.93, P < 0.01) and in the severe cases than the
      slight cases (chi2 = 4.58, P < 0.05). The severe rates of malaria cases were
      70.4% and 82.9% in the low educated group and the high educated group,
      respectively (chi2 = 7.02, P < 0.01). Non-condition regression analysis showed
      that there were three influence factors which affected severe malaria, including
      whether or not self-treatment instead of seeing doctor when being fever; whether
      or not having health education before going abroad; whether or not considering
      malaria of the initial diagnosis doctor. CONCLUSION: It is very important to
      strengthen the personnel abroad malaria health education, the malaria blood smear
      microscopic inspection in medical institutions, and the initial diagnosis
      doctor's awareness on malaria.

PMID- 24024445
TI  - [Deltamethrin resistance, metabolic detoxification enzyme and kdr mutation in
      Anopheles sinensis in region along Huaihe River in Anhui Province].
AB  - OBJECTIVE: To understand the deltamethrin resistance level, GTS and P450
      metabolic detoxification enzyme activities, and mutations in the para-type sodium
      channel gene that confers knockdown resistance (kdr) in Anopheles sinensis
      mosquitoes from malaria endemic areas along the Huaihe River in Anhui Province,
      China. METHODS: An. sinensis adult mosquitoes were collected in Lilou, Mohekou
      and Tuohu townships of Bengbu City, Anhui Province from August to September,
      2011. The insecticide resistance bioassays were performed on adult mosquitoes by
      using the standard WHO susceptibility test with diagnostic concentrations of
      deltamethrin 0.05%, and the mosquito resistance status was classified based on
      the WHO resistance classification criteria. The metabolic detoxification enzyme
      activities were measured in randomly selected mosquitoes, and the IIS6 region of
      the para-type sodium channel gene was amplified by PCR and sequenced to detect
      mutations at the codon 1014. RESULTS: The knockdown rates within 60 min exposure
      to deltamethrin test paper were 4.1%, 7.0% and 8.2%, and the mortality rates were
      8.2%, 12.0% and 12.8% for mosquitoes collected from Lilou, Mohekou and Tuohu
      townships, respectively. These three populations were classified as highly
      resistant populations based on the WHO resistance classification criteria. The
      GST and P450 enzyme activities of the three populations were significantly higher
      than those of the susceptible laboratory population (P < 0.001). L1014C and
      L1014F mutations were detected, and the wild type homozygote kdr genotype was not
      found. These three populations exhibited a small but insignificant difference in
      kdr allele frequencies. No mutation was found in the laboratory susceptible
      mosquitos. CONCLUSION: The An. sinensis mosquito populations from the regions
      along the Huaihe River in Anhui Province are strongly resistant to pyrethroid
      insecticides, and exhibit significantly higher metabolic detoxification enzyme
      activities than the laboratory susceptible population. The high frequency of kdr
      mutation is identified in the mosquito populations from the region along the
      Huaihe River in Anhui Province, China.

PMID- 24024446
TI  - [Correlation between soil-transmitted nematode infections and children's growth].
AB  - OBJECTIVE: To understand the infection status of soil-transmitted nematodes in
      southwest China and the correlation between soil-transmitted nematode infections
      and children's growth. METHODS: The prevalence of soil-transmitted nematode
      infections was determined by Kato-Katz technique, and in part of the children,
      the examination of Enterobius vermicularis eggs was performed by using the
      cellophane swab method. The influencing factors were surveyed by using a
      standardized questionnaire. The relationship between soil-transmitted nematode
      infections and children's growth was analyzed by the ordinary least square (OLS)
      method. RESULTS: A total of 1 707 children were examined, with a soil-transmitted
      nematode infection rate of 22.2%. The results of OLS analysis showed that there
      existed the negative correlation between soil-transmitted nematode infections and
      the indexes of children's growth including BMI, the weight-for-age Z score and
      height-for-age Z score. Furthermore, other correlated variables included the age,
      gender, educational level of mother and raising livestock and poultry, etc.
      CONCLUSIONS: Children' s retardation is still a serious issue in the southwest
      poor areas of China and correlated with the infections of soil-transmitted
      nematodes. For improving children's growth, it is greatly significant to enhance
      the deworming and health education about parasitic diseases in mothers.

PMID- 24024447
TI  - [Diagnosis and treatment of one case of imported schistosomiasis haematobia].
AB  - The therapeutic process of one case of schistosomiasis haematobia indicates that
      the health education should be strengthened between both doctors and patients, so
      as to reduce the rates of missed diagnosis and misdiagnosis. The serum
      immunological diagnosis of schistosomiasis japonica is helpful in the diagnosis
      and treatment evaluation of schistosomiasis haematobia, and praziquantel
      treatment is efficient, but more cases are needed to be summarized for the sake
      of fair use.

PMID- 24024448
TI  - [Geographic distribution and gene sequencing of Paragonimus westermani in some
      areas of Guangdong Province].
AB  - OBJECTIVE: To investigate the current distribution of Paragonimus westermani in
      Guangdong Province. METHOD: Snails and crabs collected from mountain streams in
      regional survey sites were dissected to detect cercarial and metacercarial
      infections of P. westermani. Domestic cats and dogs artificially infected with
      the collected metacercariae were also dissected to detect adult worms of P.
      westermani. The COI and ITS2 gene sequences of those adult worms were compared
      with those of known Paragonimus specimen deposited in the GenBank. RESULTS: All
      of the first intermediate hosts in five survey sites of Liangkou, Nankun,
      Mountain, Dadong, Muxi, Guowu, were identified as Semisulcospira libertina, whose
      cercariae infection rates were 0.33%, 0.15%, 0.058%, 0.10%, and 0.05%,
      respectively; the second intermediate hosts in above five sites were all
      identified as Sinopotamon denticulatum, whose metacercariae infection rates were
      100%, 100%, 38.09%, 55.36%, and 65.26%, respectively. The numbers of
      metacercariae in the five sites were 79.4, 105.66, 9.16, 16.18, and 15.6 per
      positive crab, respectively, and 11.12, 7.87, 0.58, 0.69, and 0.85 per gram of
      crab, respectively. All the metacercariae were identical to those of P.
      westermani. Adult worms and eggs of P. westermani were found in both reservoir
      hosts of domestic cats and dogs infected artificially. By comparing the COI genes
      of five representative samples from each survey site with that of Paragonimus
      #AF219379.21, AF540958.1 from GenBank, we found out the homology to be 99%, 99%,
      99%, 98%, and 99%, respectively. In addition, a comparison of the ITS2 gene
      sequences between the above five samples and Paragonimus #DQ836243.1, DQ351845.1,
      AB354217.1 from GenBank revealed 98%, 99%, 98%, 98%, and 98% gene homology,
      respectively. CONCLUSION: Two ultra-high and three high endemic areas of P.
      westermani are discovered in Guangdong Province. No obvious differences were
      found among the types of P. westermani in the above five endemic areas.

PMID- 24024449
TI  - [Effect of radix sophorae flavescentis (RSF) mixture on mast cells in jejunal
      mucosa of mice infected by Cryptosporidium].
AB  - OBJECTIVE: To elucidate the role of mast cells (MC) activation in the jejunal
      mucous membrane in the pathogenesis of cryptosporidiosis (CPS) and explore the
      mechanism of prevention and treatment of radix sophorae flavescetis(RSF) mixture
      on CPS. METHODS: A total of 30 healthy male BALB/c mice were randomly divided
      into a normal control group, CPS model control group and RSF mixture experimental
      group. The mice of CPS model were inoculated intragastrically with 1 x 10(5)
      Cryptosporidium oocyst (CSO). The mice in the RSF mixture experimental group were
      treated with inoculation of RSF mixture (0.2 ml doses) twice one week for three
      weeks continuously after CPS models were established. Pathological changes of the
      jejunal mucosa membrane were observed by a light microscope. The MCs were stained
      by toluidine blue, the number of mast cells was recorded and the changes of
      degranulation were observed. RESULTS: The HE staining showed inflammatory
      pathological changes in the jejunal mucosa membrane of the CPS model control
      group. After three-week treatment of RSF mixture, the small intestine epithelium
      was integrated on the whole. The toluidine blue stain showed the number of mast
      cell in submucosa and muscular layer of the jejunal mucous membrane increased
      significantly in the model control group (12.80 +/- 0.84) compared with those of
      the normal control group (1.60 +/- 0.89) (P < 0.01) and an obvious degranulation
      was seen in the CPS model control group. The number of mast cells of the mice in
      the RSF mixture experimental group decreased significantly (P < 0.01) and the
      number (2.00 +/- 0.71) and morphous were closed to the normal after
      administration for three weeks. CONCLUSIONS: MC activation is involved in the
      intestinal inflammatory response caused by Cryptosporidium. RSF mixture could
      decline the number of MC, inhibit the activation and degranulation of MC in the
      jejunal mucosa membrane of CPS mice to reduce inflammation and repair the damaged
      intestinal mucosa, which may realize the purpose of treatment of CPS.

PMID- 24024450
TI  - [Effect comparison between two ELISA kits in IgG antibody detection of
      Echinococcus granulosus].
AB  - OBJECTIVE: To compare the effects of two ELISA kits on IgG antibody detection of
      human Echinococcus granulosus. METHODS: A Total of 134 sera of patients with
      echinococcosis, paragonimiasis westermani, clonorchiasis sinensis,
      schistosomiasis japonica, and cysticercosis cellulosae, and normal persons were
      detected by two IgG ELISA kits produced by different companies. Furthermore, the
      specificity, sensitivity and cross reactivity were counted and analyzed
      statistically. RESULTS: The sensitivity and specificity were extremely high of
      the two kits as 100.00%. The cross-reactivity rates were 25.00% (paragonimiasis
      westermani), 26.09% (clonorchiasis sinensis), 10.00% (schistosomiasis japonica),
      and 87.5% (cysticercosis), respectively, by using the kit produced by the
      Combined Company in Shenzhen; the cross-reactivity rates were 5.00%
      (paragonimiasis westermani), 13.04% (clonorchiasis sinensis), 20.00%
      (schistosomiasis japonica), and 93.75% (cysticercosis) respectively, by using the
      kit produced by Haitai Company in Zhuhai. In addition, there was a significant
      difference of Paragonimus westermani detection (P < 0.05), but the rests had no
      statistically significant differences (all P > 0.05) between the two kits.
      CONCLUSION: Both ELISA kits on IgG antibody detection of human Echinococcus
      granulosus have the advantages of a high sensitivity, specificity, convenience
      and high-speed. However, it is also in urgent need to further solve the cross
      reactivity of Echinococcus granulosus with other parasites, in order to improve
      the accuracy of early diagnosis.

PMID- 24024451
TI  - [Prediction of hookworm incidence with time-series model in Jiangsu Province].
AB  - OBJECTIVE: To explore the feasibility of autoregressive integrated moving average
      (ARIMA) to predict the infection rates of hookworm in Jiangsu Province. METHODS:
      From 1990 to 2006, the infection rates of hookworm were used for a training data
      set. As to obtain a stationary data set, the training data set was second-order
      differenced using the version SAS 9.0. The model parameters were screened by
      using the minimum information criterion. The ARIMA model was constructed to
      predict the infect rates of hookworm form 2007 to 2011. RESULTS: The time-series
      model ARIMA (1, 2, 0) was confirmed preliminarily. The model fitted well the
      training data set. The predictive infection rates were main accordance with the
      actual status of hookworm from 2007 to 2011, and the most minimum error was only
      9.23%. CONCLUSION: The model constructed has a good predictive effect and applied
      value for control of hookworm.

PMID- 24024452
TI  - [Effect of comprehensive schistosomiasis control measures with focus on buffalo
      and sheep removal in Anxiang County].
AB  - OBJECTIVE: To understand the effect of comprehensive schistosomiasis control
      measures with focus on buffalo and sheep removal in Anxiang City, Dongting Lake
      area. METHODS: The data of buffalo and sheep removal, routine schistosomiasis
      control measures such as disease detection and treatment, Oncomelania snail
      survey and control, as well as health education were collected and analyzed in
      Anxiang County, Hunan Province from 2004 to 2012. RESULTS: The schistosome
      infection rates of people, domestic animals and snails decreased from 11.23%,
      17.06% and 1.07% in 2004 when the comprehensive measures had not been implemented
      to 0.58%, 0 and 0 in 2012, respectively. The average density of infected snails
      decreased from 0.003 4 snails/0.1 m2 to 0. CONCLUSION: The comprehensive control
      measures with focus on buffalo and sheep removal are significantly effective, and
      can control the transmission of schistosomiasis in marshland and lake regions.

PMID- 24024453
TI  - [Effect of control interventions for intestinal nematodiasis in areas with low
      prevalence in Changzhou City].
AB  - OBJECTIVE: To evaluate the effect of control interventions for intestinal
      nematodiasis in areas with low prevalence, so as to explorethe effective measures
      for the control of intestinal nematode infections in Changzhou City, Jiangsu
      Province, China. METHODS: The residents in Wujin, Jintan, Tianning districts were
      selected as monitor subjects and the infections of intestinal nematodes were
      investigated with Kato-Katz technique or the transparent tape anal swab method.
      The results were analyzed statistically and the cost-effectiveness was also
      analyzed. RESULTS: A total of 26 966 people were investigated and the total
      infection rate of intestinal nematodes was 0.37% (99/26 966). The infection rates
      of the local residents and floating population were 0.31% (63/20 267) and 0.55%
      (37/6 699), respectively, and the former was lower the latter (P < 0.01); the
      infection rates of urban residents and rural residents were 0.29% (44/15 328) and
      0.47% (55/11 638),respectively, and the former was lower than the latter (P <
      0.05). The 3 jurisdictions used different interventions, and the costs of 1%
      infection rate drop were 15.9 yuan/thousand people in Wujin District, 1.9
      yuan/thousand people in Jintan District, and 1.7 yuan/thousand people in Tianning
      District. The cost in Jintan was lower than that in Wujin, but the infection rate
      drop in Jintan was more than that in Wujin. CONCLUSION: The floating population
      as well as the rural residents is still the focus and difficulty of the
      intestinal nematodiasis control. The deworming and health education are the main
      interventions in the key population.

PMID- 24024454
TI  - [Effect of schistosomiasis comprehensive control in Linxiang City, 2004-2012].
AB  - OBJECTIVE: To evaluate the effect of schistosomiasis comprehensive control in
      Linxiang City. METHODS: The data of the endemic situation and control measures of
      schistosomiasis in Linxiang City from 2004 to 2012 were collected and analyzed,
      so as to assess the effect of schistosomiasis comprehensive control. RESULTS:
      Since 2005, a total of 14 610 household latrines improved, 9 782 biogas pools
      were built, 40.65 km river and river banks were protected, 809 cattle were
      eliminated, 23.30 hm2 pond were dug, 15.18 km ditches were hardened, 18.10 hm2
      land were polished, more than 20 safe drinking water projects were constructed,
      and the beneficiary population reached 68 400 people. The human and cattle
      infection rate reduced from 2.07% and 3.95% in 2004 to 0.46% and 1.35% in 2012,
      with reduction rates of 77.78% and 65.82%, respectively. The living Oncomelania
      snail density and snail infection rate showed an overall decline tendency, which
      reduced from 0.114 4 snails/0.1 m2 and 0.19% in 2004 to 0.0 056 snails/0.1 m2 and
      0 in 2012, with reduction rates of 95.10% and 100%, respectively. CONCLUSION: The
      promotion and implementation of the schistosomiasis comprehensive control
      measures with emphasis on control of the source of infection control is the key
      to further expand the achievements of schistosomiasis control in Linxiang City.

PMID- 24024455
TI  - [Surveillance of endemic situation of schistosomiasis in a national surveillance
      site in Jiangling County from 2005 to 2011].
AB  - OBJECTIVE: To understand the dynamics of schistosomiasis japonica in a national
      surveillance site in Jiangling County, Hubei Province, China, so as to provide
      the evidence for formulating the intervention strategy of schistosomiasis control
      in the whole county. METHODS: The surveillance was performed in the surveillance
      village according to The National Surveillance Scheme of Schistosomiasis
      japonica, and the results were analyzed statistically from 2005 to 2011. RESULTS:
      The schistosome infection rates in residents and cattle decreased from 1.83% and
      11.67% in 2005 to 0.91% and 0 in 2011, respectively. The density of living
      Oncomelania hupensis snails, the density of infected snails, and the infection
      rate of snails decreased from 4.02/0.1 m2, 0.014 5/0.1 m2, and 0.36% in 2005 to
      0.70/0.1 m2, 0.000 3/0.1 m2, and 0.04% in 2011, respectively. CONCLUSIONS: The
      transmission of schistosomiasis in the surveillance site shows a gradually
      decreasing trend year by year, but the prevalence is still not stable. Therefore,
      the comprehensive interventions with the main effort for the infectious source
      control still need to be strengthened.

PMID- 24024456
TI  - [Parasitological characteristics, epidemiological and clinical features, and
      current control approaches for three major kinds of human schistosomiasis].
AB  - Schistosomiasis is a tropical disease, which could do serious damage to the
      people's health, and it hinders the development of the social economy but may be
      neglected. After a positive control, some countries and regions have blocked the
      spread of schistosomiasis. However, in the past few years, with the development
      of social economy, due to the global movement of people, schistosomiasis not only
      poses a threat to control areas, but also may cause new endemic areas. This
      article reviews the parasitological characteristics, clinical manifestations,
      epidemiological situation, and control approaches of three major kinds of human
      schistosomiasis, schistosomiasis japonica, schistosomiasis haematobia, and
      schistosomiasis mansoni.

PMID- 24024457
TI  - [Current situation of endemic status, prevention and control of neglected
      zoonotic diseases in China].
AB  - Neglected zoonotic diseases not only threaten the health of human, especially to
      the livestock keepers in poverty-stricken areas but also cause great economic
      losses to the animal husbandry. This paper reviews the current situation of the
      endemic status, prevention and control of neglected zoonotic diseases existing in
      China including rabies, bovine tuberculosis, brucellosis, anthrax, leptospirosis,
      echinococcosis, cysticercosis, leishmaniasis and fascioliasis, so as to provide
      the basic information for better controlling, even eliminating, the neglected
      zoonotic diseases in China.

PMID- 24024458
TI  - [Research progress on malaria vector control].
AB  - Vector control plays a crucial role in the stages of malaria control and
      elimination. Currently, it mainly relies on the chemical control methods for
      adult mosquitoes in malaria endemic areas, however, it is undergoing the serious
      threat by insecticide resistance. In recent years, the transgenic technologies of
      malaria vectors have made a great progress in the laboratory. This paper reviews
      the challenges of the traditional methods and the rapid developed genetic
      modified technology in the application of vector control.

PMID- 24024459
TI  - [Progress in application of genetic control of mosquitoes].
AB  - With the specific, environmental-friendly, fast and efficient characteristics,
      the genetic control of mosquitoes has been preliminary shown a good effect.
      However, the prejudices and misunderstandings to the genetic control limit its
      popularization and application. Therefore, in order to re-recognize and take full
      advantage of this method, the recent progresses towards applying the genetic
      control of mosquitoes are reviewed.

PMID- 24024460
TI  - [Molluscicidal effect and cost-effectiveness of suspension concentrate of
      metaldehyde and niclosamide in the field in Honghu City].
AB  - OBJECTIVE: To assess the molluscicidal effect and cost-effectiveness of
      suspension concentrate of metaldehyde and niclosamide (MNSC) in the field, so as
      to evaluate the possibility of popularization and application value. METHODS: 26%
      MNSC and 50% wettable powder of niclosamide (WPN) were used for Oncomelania snail
      control with the spraying method in the field, and the 15-d molluscicidal effects
      and costs were investigated. RESULTS: Fifteen days after the spraying, in the
      beach of Dongjing River, the snail death rates of MNSC and WPN were 89.40% and
      88.08%, respectively, and the density reduction rates of MNSC and WPN were 92.35%
      and 91.67%, respectively. In the marshland of Honghu Lake, the snail death rates
      of MNSC and WPN were 86.59% and 87.01%, respectively, and the density reduction
      rates of MNSC and WPN were 90.05% and 91.71%, respectively. There was no
      significant difference in the molluscicidal effect between two drugs (P > 0.05).
      The cost of MNSC used in 100 m2 was 15.03 Yuan, while the cost of WPN used in 100
      m2 was 16.29 Yuan. CONCLUSION: MNSC has high molluscicidal efficacy, low cost and
      low impact on environments, which possesses of popularization and application
      value in the field.

PMID- 24024461
TI  - [Simulation experiment of survival and reproduction of artificially imported
      Oncomelania snails in Qingpu District, Shanghai].
AB  - OBJECTIVE: To understand the survival of imported Oncomelania snails in new
      environments with different densities in waterway net region, Qingpu District,
      Shanghai. METHODS: The snails collected from Guichi, Anhui Province were put into
      the ponds of 4 square meters and each had 25, 50, 100, 200, 400 and 800 pairs of
      snails, respectively. During the next 2 years, the temperature, humidity, the
      activities of snails and their second birth snails were investigated each day.
      All the data were analyzed statistically. RESULTS: The highest number of snails
      appeared from May to June on the surface of soils in different densities. The
      average numbers of snails were 2.0%-12.7% of whole put in snails, and the numbers
      of offspring were less than 2% of the whole put in snails. CONCLUSION: The
      survival and reproduction of artificially imported Oncomelania snails from
      Guichi, Anhui Province is not good in Qingpu District, Shanghai.

PMID- 24024462
TI  - [Clinical analysis of 91 cases of imported falciparum malaria from Africa].
AB  - OBJECTIVE: To explore the clinical characteristics, early diagnosis, and
      treatment of patients with imported falciparum malaria from Africa. METHODS: The
      clinical data of 91 imported falciparum malaria cases were analyzed by
      retrospective study. RESULTS: All the 91 cases had the history of mosquito bites.
      The clinical manifestation of these cases varied, including fever, headache,
      chill, diarrhea, anemia, thrombocytopenia, proteinuria, damage of liver function,
      abdominal ultrasonographic presentations (enlarged liver and spleen). All the
      patients were successfully treated with the combination therapy of artemether and
      primaquine. CONCLUSION: The key procedures for treating imported falciparum
      malaria are earlier diagnosis and effective therapy. The combination therapy with
      artemether and primaquine shows a high efficacy and low side effect and low
      relapsed rate.

PMID- 24024463
TI  - [Relationship between schistosome serum test positive rate of residents and
      positive rate of Oncomelania snails in a national schistosomiasis surveillance
      site of Jiangling County].
AB  - OBJECTIVE: To explore the relationship between schistosome serum test positive
      rate of residents and positive rate of Oncomelania snails in a national
      schistosomiasis surveillance site of Jiangling County. METHODS: According to the
      national schistosomiasis monitoring scheme, the data of surveillance including
      the schistosome serum test positive rates of residents and positive rates of
      Oncomelania snails from 2005 to 2011 were collected and analyzed statistically.
      RESULTS: From 2005 to 2011, the schistosome serum test positive rates of
      residents were 26.09%, 11.84%, 10.37%, 10.09%, 12.08%,9.61%, and 6.00%,
      respectively; the schistosome positive rates of Oncomelania snails were 0.36%,
      0.08%, 0.15%, 0.129%, 0.067%, 0.091%, and 0.045%, respectively. There was a
      significant positive correlation between them (r = 0.929, P < 0.01). CONCLUSION:
      There is a positive correlation between schistosome serum test positive rate of
      residents and positive rate of Oncomelania snails. Therefore, we should
      strengthen the snail control.

PMID- 24024464
TI  - [Detection of four parasitic infections using ELISA].
AB  - OBJECTIVE: To study the detection effects of ELISA for the infections of
      Cysticercus, Echinococcosus, Paragonimus westermani and Sparganum mansoni in
      order to improve diagnosis. METHODS: The patients who admitted to Jiangsu
      Institute of Parasitic Diseases from 2008 to 2001 were selected as the subjects
      and their sera were detected for IgG against Cysticercus, Echinococcosus, and
      Paragonimus westermani from January 2008 to March 2011, and IgG against Sparganum
      mansoni since June, 2011 by ELISA. RESULTS: A total of 282 cases were detected,
      and 88 of them were found one or two positive results, and the total positive
      rate was 31.2%. There were 39, 2, 21, and 3 cases of positive IgG of Cysticercus,
      Echinococcosus, Paragonimus westermani and Sparganum mansoni, respectively. There
      were 15 cases of positive IgG to both Cysticercus and Echinococcosus; there were
      5 cases of positive IgG to both Cysticercus and Paragonimus westermani; there
      were 3 cases of positive IgG to both Echinococcosus and Paragonimus westermani.
      The cross reactions occurred in 23 serum samples among 88 positive samples with a
      cross reaction rate of 26.1%. CONCLUSION: There still exist a certain number of
      patients with parasitic diseases, and the cross reaction may occur in the
      detection process of IgG to Cysticercus, Echinococcosus, Paragonimus westermani
      and Sparganum mansoni by ELISA.

PMID- 24024465
TI  - [A case of imported schistosomiasis haematobia first reported in Fujian
      Province].
AB  - The first case of imported schistosomiasis haematobia in Fujian Province was
      detected and the patient was cured following treatment with praziquantel.

PMID- 24024466
TI  - Association study of the 2-bp deletion polymorphism in exon 6 of the CHRFAM7A
      gene with idiopathic generalized epilepsy.
AB  - There is evidence of linkage between the 15q13-q14 locus, containing the gene
      encoding the alpha7 subunit (CHRNA7) of the neuronal nicotinic acetylcholine
      receptor (nAChR) and its partially duplicated isoform (CHRFAM7A), and epilepsy.
      Additionally, a 2-bp deletion polymorphism (c.497-498delTG; rs67158670) in
      CHRFAM7A, resulting in a frame shift and truncation of the protein product, is
      associated with some neurological diseases. This study was designed to explore
      the possibility of an association of the c.497-498delTG polymorphism of CHRFAM7A
      with idiopathic generalized epilepsies (IGEs) in Polish children and young
      patients. The study included 197 IGE patients and 258 unrelated healthy
      individuals. The frequency of the CHRFAM7A c.497-498delTG polymorphism was
      determined in each group using heteroduplex analysis. An association between the
      c.497-498delTG polymorphism of CHRFAM7A and IGE was evidenced. It was
      demonstrated that the frequency of the CHRFAM7A 2-bp deletion carriers was
      significantly lower in the IGE patients than in the control group. The observed
      frequency of 2-bp deletion carriers was high in IGE subjects (64%), but
      significantly higher in control subjects (76%). Carriers of at least one copy of
      the -2 bp allele had halved their risk of IGE susceptibility (delTG/delTG and
      delTG/wild-type versus wild-type/wild-type: odds ratio=0.55; 95% confidence
      intervals=0.365-0.827; p=0.004). Moreover, it has been demonstrated that this
      polymorphic variant is associated with the c.524-12_524-11insGTT variation
      (rs10649395) in intron 7 of CHRFAM7A. Our study substantiates the involvement of
      the alpha7 subunit of nAChR in the pathophysiology of IGEs and indicates that the
      CHRFAM7A c.497-498TG deletion or a nearby polymorphism may play a role in the
      pathogenesis of IGE. Further work should concentrate on ascertaining the exact
      mechanism of this polymorphism's effect and its relationship with IGE. 

PMID- 24024467
TI  - Structural and dynamic properties of thymopoietin mimetics.
AB  - We propose a hypothesis that the T-cell receptor is a possible target of thymic
      hormones. We modelled the conformational dynamics of thymopentin and its
      structural variants in solution, as well as the interactions of these short
      peptides with the proposed molecular target. Thymopentin is a five-amino-acid
      fragment of the thymic hormone thymopoietin (residues 32 to 36) that reproduces
      the immunomodulatory activity of the complete hormone. Using molecular dynamics
      and flexible docking methods, we demonstrated high-affinity binding of
      thymopentin and its prospective mimetics with the T-cell receptor. The calculated
      biological activity spectra of thymopentin and its two promising modifications
      can be used in immunomodulatory activity screenings with live systems. 

PMID- 24024468
TI  - Synthesis and bidirectional frequency tuning of cantilever-shape nano resonators
      using a focused ion beam.
AB  - The synthesis of cantilever-shape nano resonators and their resonant frequency
      tunings in both upward and downward directions have been demonstrated using FIB
      CVD (focused ion beam-chemical vapor deposition). The in situ experimental
      observations of mechanical resonances as well as cutting and adding of resonator
      materials have been accomplished inside the FIB vacuum chamber. Extending the
      length of the cantilever-shape resonator by 500 nm scale using either the same
      material or alternating different materials effectively reduced resonant
      frequency. On the other hand, direct cutting and gradual trimming of the end
      point of nano resonator increases its resonant frequency. This simple yet
      versatile synthesis and frequency tuning scheme could be applicable to both
      constructing micro/nano scale resonators and tuning nanostructures with reduced
      efforts and enhanced efficiency. 

PMID- 24024469
TI  - Perturbation of Brachypodium distachyon CELLULOSE SYNTHASE A4 or 7 results in
      abnormal cell walls.
AB  - BACKGROUND: Cellulose is an integral component of the plant cell wall and
      accounts for approximately forty percent of total plant biomass but understanding
      its mechanism of synthesis remains elusive. CELLULOSE SYNTHASE A (CESA) proteins
      function as catalytic subunits of a rosette-shaped complex that synthesizes
      cellulose at the plasma membrane. Arabidopsis thaliana and rice (Oryza sativa)
      secondary wall CESA loss-of-function mutants have weak stems and irregular or
      thin cell walls. RESULTS: Here, we identify candidates for secondary wall CESAs
      in Brachypodium distachyon as having similar amino acid sequence and expression
      to those characterized in A. thaliana, namely CESA4/7/8. To functionally
      characterize BdCESA4 and BdCESA7, we generated loss-of-function mutants using
      artificial microRNA constructs, specifically targeting each gene driven by a
      maize (Zea mays) ubiquitin promoter. Presence of the transgenes reduced BdCESA4
      and BdCESA7 transcript abundance, as well as stem area, cell wall thickness of
      xylem and fibers, and the amount of crystalline cellulose in the cell wall.
      CONCLUSION: These results suggest BdCESA4 and BdCESA7 play a key role in B.
      distachyon secondary cell wall biosynthesis.

PMID- 24024471
TI  - Role of polymorphisms in BCL-2 and BAX genes in modulating the risk of developing
      non-Hodgkin lymphoma.
AB  - The aim of this study was to investigate whether polymorphisms of - 938C/A and
      Thr43Ala in the BCL-2 gene and G - 248A in the BAX gene are associated with the
      risk of developing non-Hodgkin lymphoma (NHL). We genotyped polymorphisms of -
      938C/A and Thr43Ala in the BCL-2 gene and G-248A in the BAX gene among 424
      patients with NHL and 446 controls. We found that the - 938AA genotype of the
      BCL2 gene was significantly associated with the risk of developing NHL (p <
      0.001) and this genotype was associated with advanced stage (p = 0.01).
      Meanwhile, individuals having - 248AG + AA genotypes were significantly
      associated with an increased risk of NHL (p = 0.01), and these genotypes were
      associated with larger tumor size (p = 0.02). The present study demonstrated that
      the - 938AA genotype of the BCL-2 gene and - 248AG + AA genotype of the BAX gene
      may be susceptible genotypes for NHL. There appeared to be an impact of the BCL2 
      938AA genotype on advanced stage and - 248AG + AA genotypes on tumor size in
      NHL.

PMID- 24024470
TI  - Clinical significance of pre- and 1-year post-transplant serum ferritin among
      adult transplant recipients.
AB  - To clarify the significance of post-transplant serum ferritin (SF), we
      retrospectively assessed pre- and post-transplant SF. Among 256 patients
      undergoing allogeneic stem cell transplant (SCT) for hematologic malignancies
      between 2000 and 2011, those who had relapsed within 1 year were excluded, and
      110 patients surviving for more than 1 year were included in the analysis. The
      cut-off value of SF was 1000 ng/mL, and four pre- and post-SF groups were
      defined: low-low (n = 62), low-high (n = 12), high-low (n = 13) and high-high (n
      = 23). Outcomes at 5 years for each group were as follows: overall survival (OS)
      88.2, 38.1, 92.3 and 76.7%, respectively, p = 0.004, and non-relapse mortality
      (NRM) 11.3, 53.6, 7.7 and 18.9%, respectively, p = 0.037. Patients receiving
      larger transfusion volumes or developing chronic graft-versus-host disease (GVHD)
      demonstrated higher 1-year SF values. In multivariate analysis for OS and NRM,
      low-high SF remained a significant predictor of OS (hazard ratio [HR] = 3.49, 95%
      confidence interval [CI]: 1.10-11.0, p = 0.032) and NRM (HR = 2.95, 95%CI: 1.04
      8.36, p = 0.041). These results suggest that the elevation of SF at 1 year after
      SCT, which may reflect transfusion and the development of chronic GVHD, may have
      an aggravating influence on outcomes after SCT. This study provides a clue to
      clarifying the clinical significance of SF in a transplant setting.

PMID- 24024472
TI  - Target-directed development and preclinical characterization of the proposed
      biosimilar rituximab GP2013.
AB  - Biosimilar development involves a target-directed iterative process to ensure a
      similar product to the originator. Here we report the preclinical development of
      the proposed biosimilar rituximab (GP2013). Post-translational modifications and
      bioactivities of GP2013 versus originator rituximab were engineered and monitored
      to ensure similar pharmacological profiles. Antibody-dependent cellular
      cytotoxicity (ADCC) was used to illustrate how different glycosylation patterns
      and structure-function relationships were controlled during process development.
      Pharmacological comparability between GP2013 and originator rituximab were
      confirmed in preclinical studies using clinical scale drug product. Similar in
      vitro ADCC potency was demonstrated when compared in a dose-response manner
      against two lymphoma cell lines using freshly purified human natural killer (NK)
      cells. In vivo efficacy was demonstrated in two well characterized mouse
      xenograft models, testing at sensitive sub-therapeutic dose levels.
      Pharmacokinetics and pharmacodynamics (CD20 cell depletion) were likewise
      comparable in cynomolgus monkeys. This preclinical comparability exercise
      confirms that GP2013 and originator rituximab are pharmacologically similar.

PMID- 24024473
TI  - Large vessel vasculopathy in Epstein-Barr virus-positive diffuse large B-cell
      lymphoma.

PMID- 24024474
TI  - Conditioning regimen with BCNU, etoposide, cytarabine and melphalan plus
      amifostine for outpatient autologous stem cell transplant: feasibility and
      outcome in 97 patients with lymphoma.

PMID- 24024475
TI  - Nilotinib monotherapy induced complete remission in pediatric Philadelphia
      chromosome-positive acute lymphoblastic leukemia resistant to imatinib and
      dasatinib.

PMID- 24024476
TI  - Vancomycin-resistant enterococci infection: not just for the transplanted.
AB  - Vancomycin-resistant enterococcal (VRE) blood stream infections (BSIs) pose
      significant hazards to patients with hematologic malignancy. We compared and
      examined VRE BSI rates, patient characteristics and clinical outcomes for two
      cohorts of patients: those who did and did not undergo hematopoietic cell
      transplant (HCT). In this single institution study, we retrospectively analyzed
      records of consecutive patients from 1998 through 2011. Over this 14-year period,
      VRE was identified in 14% of all BSIs in patients with HCT with a cumulative rate
      of 1.9% (48/2581 BSIs/patients). VRE was identified in 10% of all BSIs in non-HCT
      patients with a cumulative rate of 1.1% (35/3154 BSIs/patients). Transplant
      patients who developed VRE BSI tended to be younger, hospitalized more
      frequently, were exposed to vancomycin therapy frequently, and were more likely
      to have had a central venous catheter removed. VRE remains a significant cause of
      morbidity and mortality, as 22 deaths were directly or indirectly attributed to
      this infection. Both HCT and non-HCT patients are susceptible to VRE infection
      and are equally at risk for adverse outcomes related to VRE BSI.

PMID- 24024477
TI  - Inhibition of NADPH oxidase by vaspin may prevent progression of atherosclerosis.

PMID- 24024478
TI  - The rate of seat belt use and its related factors among car drivers in Tehran,
      Iran after imposing new regulations.
AB  - The incidence of road crash deaths is high in Iran. Seat belts can reduce the
      risk of death or serious injury. This study aimed to estimate the rate of seat
      belt use and its related factors for car drivers in Tehran, Iran after
      proclamation of the 2011 legislation. A roadside observational study was
      conducted in 2012 and 10,752 cars and taxis commuting in different streets of
      Tehran were screened in regard to drivers' seat belt wearing. Other variables
      including gender, age range, type of street, district, time of day and day of
      week were also collected. The rate of seat belt use was 70.9%, and was
      significantly higher in females, elders and on freeways and significantly less in
      afternoon hours, side streets and in taxi drivers. The rate of seat belt use in
      Tehran (a representative of Iran) is still low despite the implementation of new
      legislations. More initiatives are needed to increase this rate especially in
      certain groups and areas. 

PMID- 24024479
TI  - Patient satisfaction and esthetic outcome after immediate placement and
      provisionalization of single-tooth implants involving a definitive individual
      abutment.
AB  - OBJECTIVES: To assess patient satisfaction and esthetic outcome after immediate
      placement and provisionalization of single-tooth implants involving a definitive
      individual abutment and a provisional crown followed by later placement of a
      definitive crown. MATERIALS AND METHODS: In private practice, a single-tooth
      implant was placed immediately after tooth extraction in the esthetic zone of 54
      patients. A definitive individual abutment and a provisional crown were mounted
      in the same visit. The definitive crown was placed after a mean period of 7
      months. After a mean follow-up period of 33 months, the subjective and
      professional evaluation of the total implant treatment, peri-implant soft
      tissues, and implant crown were assessed on a 10-cm visual analog scale (VAS).
      The professional esthetic treatment outcome was also evaluated using pink
      esthetic score (PES), white esthetic score (WES), and total score of PES/WES.
      RESULTS: The evaluation of total implant treatment, peri-implant soft tissues,
      and implant crown demonstrated a significantly higher subjective than
      professional score for all 3 parameters (P < 0.001), for example, for the overall
      treatment, the mean scores were 9.4 and 7.0, respectively. A significant positive
      correlation was revealed between the professional VAS scores and the PESs and
      WESs. CONCLUSIONS: Immediate placement and provisionalization of single-tooth
      implants involving a definitive individual abutment and provisional crown
      followed by later placement of a definitive crown demonstrated high subjective
      and professional satisfaction. Generally, the professionals seem to be more
      critical than the patients. A strong correlation was observed between the
      professional VAS scores and the PES and WES scoring systems.

PMID- 24024480
TI  - Single-molecule studies of bacterial protein translocation.
AB  - In prokaryotes, a large share of the proteins are secreted from the cell through
      a process that requires their translocation across the cytoplasmic membrane. This
      process is mediated by the universally conserved Sec system with homologues in
      the endoplasmic reticulum and thylakoid membranes of eukaryotes. The Sec system
      also facilitates the membrane insertion of integral membrane proteins, an
      essential step along their folding pathway. In bacteria, the Sec system consists
      of the protein-conducting channel (SecYEG) that associates with soluble
      components, such as the motor protein SecA or translating ribosomes, and with
      integral membrane proteins, such as the heterotrimeric complex termed SecDFyajC
      and the YidC insertase. Over the past three decades, biochemical and structural
      studies have provided a comprehensive view of protein translocation, but the
      exact mechanistic details of this process remain to be resolved. For a number of
      other biomolecular systems, single-molecule biophysical analysis has efficiently
      complemented the conventional biochemical studies conducted in bulk, with high
      sensitivity measurements probing the structure and dynamics of individual
      molecules in vitro and in vivo. Here, we review recent advances in studies of
      protein translocation employing single-molecule techniques with the aim of
      resolving molecular mechanisms, thereby providing a new and detailed view of the
      process. 

PMID- 24024481
TI  - Formation of thermal coagulum on multielectrode catheters during phased
      radiofrequency energy ablation of persistent atrial fibrillation.
AB  - BACKGROUND: Radiofrequency ablation (RFA) can unfavorably cause coagulum on the
      ablation electrode. The aim of this study was to assess this phenomenon on three
      different multielectrode catheters used to treat persistent atrial fibrillation
      with duty-cycled RFA. METHODS AND RESULTS: Twenty-six consecutive patients have
      been treated with the pulmonary vein ablation catheter (PVAC) and the multiarray
      ablation catheter (MAAC). In 13 patients, additional ablation with the multiarray
      septal catheter (MASC) has been performed. The multichannel RF generator GENiusTM
      (Medtronic Inc., Minneapolis, MN, USA) independently delivered energy in a
      bipolar and unipolar mode (ratio of 4/1, 2/1, or 1/1) to any of the electrodes.
      Versions 14.2, 14.3, and 14.4 of the generator were used. Coagulum presence was
      determined postablation by careful visual inspection of the catheter electrodes.
      No coagulum formation was visualized on the PVACs. Coagulum formation was
      visualized in 59% of the electrodes of the MAACs using a 2/1 mode and the 14.2
      software version versus 69% using the 14.4 version and a 2/1 mode (P = 0.7)
      versus 14% of the electrodes applying a 1/1 ratio and the 14.4 software version
      (P < 0.001). CONCLUSIONS: Duty-cycled RFA in 2/1 bipolar/unipolar ratio generates
      a substantial frequency of coagulum formation on the multielectrode catheters
      MAAC and MASC. The use of the 14.4 version of the software to drive the RF
      generator and the use of energy in the default 1/1 bipolar/unipolar ratio could
      significantly reduce the frequency of coagulum formation, but so far, could not
      completely overcome it. The PVAC did not form coagulum, regardless of generator
      version or energy ratio used.

PMID- 24024482
TI  - Acute and subacute toxicity assessment of lutein in lutein-deficient mice.
AB  - Dietary lutein consumption is lower than the actual recommended allowances to
      prevent macular degeneration; thus dietary lutein supplements have been
      recommended. This study aimed to investigate potential adverse effect of lutein
      from Tagetes erecta in lutein-deficient (LD) male mice. Preliminary acute
      toxicity study revealed that the LD50 exceeded the highest dose of 10000 mg/kg
      BW. In a subacute study, male mice were gavaged with 0, 100, 1000 mg/kg BW/day
      for a period of 4 wk. Plasma lutein levels increased dose dependently (P < 0.01)
      after acute and subacute feeding of lutein in LD mice. Compared to the control
      (peanut oil without lutein) group, no treatment-related toxicologically
      significant effects of lutein were prominent in clinical observation, ophthalmic
      examinations, body, and organ weights. Further, no toxicologically significant
      findings were eminent in hematological, histopathological, and other clinical
      chemistry parameters. In the oral subacute toxicity study, the no-observed
      adverse-effect level (NOAEL) for lutein in LD mice was determined as 1000
      mg/kg/day, the highest dose tested. 

PMID- 24024484
TI  - Getting impatient about person-centred health care.

PMID- 24024483
TI  - Laser-assisted subepithelial keratectomy versus epipolis laser in situ
      keratomileusis for myopia: a meta-analysis of clinical outcomes.
AB  - BACKGROUND: To identify possible differences between laser-assisted subepithelial
      keratectomy and epipolis laser in situ keratomileusis for myopia. DESIGN: Meta
      analysis. PARTICIPANTS: Patients from previously reported comparative studies
      treated by laser-assisted subepithelial keratectomy versus epipolis laser in situ
      keratomileusis. METHODS: A systematic literature retrieval was conducted in the
      MEDLINE, EMBASE and Cochrane Library, up to January 2013. The included studies
      were subject to a meta-analysis using a RevMan 5.1 version software. MAIN OUTCOME
      MEASURES: The differences in efficacy, predictability, safety, epithelial healing
      time, pain perception and corneal haze formation. RESULTS: A total of six studies
      involving 517 eyes were included. There were no statistically significant
      differences in the final proportion of eyes with uncorrected visual acuity of 6/6
      or better (P = 0.43), mean postoperative uncorrected visual acuity (P = 0.53),
      final proportion of eyes with refraction within +/- 0.50 D (P = 0.62) and +/-
      1.00 D (P = 0.16) of target, final proportion of eyes losing two or more lines of
      best spectacle-corrected visual acuity (P = 1.00), healing time of corneal
      epithelium (P = 0.58), final proportion of eyes with corneal haze grade 0.5 or
      higher (P = 0.26), and corneal haze levels (P = 0.36). CONCLUSIONS: There were no
      significant differences in efficacy, predictability, safety, epithelial healing
      time and corneal haze formation between laser-assisted subepithelial keratectomy
      and epipolis laser in situ keratomileusis, but the result was limited. Future
      more data are required to detect the potential differences between the two
      procedures.

PMID- 24024485
TI  - Delivering the faecal occult blood test: More instructions than shared decisions.
      A qualitative study among French GPs.
AB  - BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. In
      France, mass screening has been established with FOBT since 2008. The
      participation rate remains too low. Previous studies were conducted to explore
      doctors' and patients' perspectives. OBJECTIVE: This study was conducted to
      explore GPs' performance during consultations in which patients ask for FOBT,
      focusing on two different aspects: the core content of the consultation and the
      communication style used between GPs and patients. METHODS: Nine purposively
      sampled GPs were asked to audiotape specific consultations. Content analysis was
      performed using Nvivo 9 software. Communication between doctors and patients was
      explored using RIAS coding. RESULTS: GPs audio taped specific parts of 35
      different consultations when they discussed and delivered the FOBT. The core
      content included primarily biomedical statements with a large portion dedicated
      to technical aspects. The communication style was not patient-centred.
      CONCLUSION: While the participation rate of mass screening in France is still
      low, the analysis of recorded consultations by French GPs confirms that the way
      of delivering FOBT can be improved.

PMID- 24024487
TI  - What can artefact analysis tell us about patient transitions between the hospital
      and primary care? Lessons from the HANDOVER project.
AB  - BACKGROUND: Hospital discharge often faces breakdowns in information,
      communication, and coordination. The European Union FP7 Health Research Programme
      commissioned the European HANDOVER Project in 2008, a three year, 3.5 million
      Euro programme to examine transitions of patient care from the hospital to the
      community care settings. Six European countries--Italy, the Netherlands, Poland,
      United Kingdom, Spain, and Sweden--participated in this collaborative study.
      OBJECTIVES: This paper highlights a multi-centre, multi-national research
      programme. We describe how HANDOVER participants conducted an 'artefact analysis'
      as one element of the mixed methods study to inform opportunities to make patient
      handovers between hospital and community care more effective. METHODS: The
      artefact analysis consisted of a four-step process to assess different tools used
      in communication and treatment and their effects on the communication processes
      between the hospital and general practice settings. RESULTS: Four themes emerged
      from our analysis: (a) The inpatient care of a patient is 'hospital centric'
      whereby the hospital 'pulls' information regarding a patient's family physician
      (b) There are rich cognitive artefacts that support the patient clinician
      encounter; c) The use of information technology does not necessarily improve the
      communication process; and (d) There is a role for the patient, albeit not
      particularly well-defined or explicit, as a conduit for essential information
      communication. CONCLUSION: Cognitive artefact analysis is an innovative method to
      provide insights into transitions of patient care. It may be most useful to think
      about interventions at both the individual patient and the system levels that
      more fully address and overcome the system issues at work.

PMID- 24024488
TI  - EQuip: European Society for Quality And Safety In Family Practice in memorial of
      Professor Helen Lester-on behalf of the EQuiP network.

PMID- 24024489
TI  - EGPRN: European General Practice Research Network EGPRN is networking in many
      ways.

PMID- 24024490
TI  - VDGM:Vasco Da Gama Movement Awards, fund and web site.

PMID- 24024492
TI  - IPCRG: International Primary Care Respiratory Group IPCRG, working locally,
      collaborating globally.

PMID- 24024494
TI  - Interaction of pristine and functionalized carbon nanotubes with lipid membranes.
AB  - Carbon nanotubes are widely used in a growing number of applications. Their
      interactions with biological materials, cell membranes in particular, is of
      interest in applications including drug delivery and for understanding the
      toxicity of carbon nanotubes. We use extensive molecular dynamics simulations
      with the MARTINI model to study the interactions of model nanotubes of different
      thickness, length, and patterns of chemical modification with model membranes. In
      addition, we characterize the interactions of small bundles of carbon nanotubes
      with membrane models. Short pristine carbon nanotubes readily insert into
      membranes and adopt an orientation parallel to the plane of the membrane in the
      center of the membrane. Larger aggregates and functionalized nanotubes exhibit a
      range of possible interactions. The distribution and orientation of carbon
      nanotubes can be controlled by functionalizing the nanotubes. Free energy
      calculations provide thermodynamic insight into the preferred orientations of
      different nanotubes and quantify structural defects in the lipid matrix. 

PMID- 24024495
TI  - Projecting social support needs of informal caregivers in Malaysia.
AB  - This article presents the findings of a self-report study of the consequences of
      being an informal caregiver in Malaysia. The aim of this exploratory study was to
      examine Malaysian efforts in assisting informal caregivers, based on an analysis
      of the issues and concerns raised by the caregivers themselves. Data were
      obtained from a cross-sectional survey of informal caregivers in 2009. This
      sample comprised parents, spouses and/or adult siblings, and adult children,
      caring for their children, spouses or siblings and parents who were chronically
      ill and/or had a disability. Of 300 prospective participants, only 175 could be
      located (58%), but all those contacted agreed to participate. Respondents were
      randomly selected and interviewed using a structured questionnaire to identify
      the emotional, financial, social and physical issues consequent upon being a
      caregiver. Most respondents reported that their care-giving responsibilities had
      impacted their emotional, financial, social and/or physical well-being.
      Inadequate and/or uncertain income was by far the greatest concern followed in
      descending order by social, physical and emotional consequences. The one-way
      analysis of variance showed significant differences among the three categories of
      caregivers with respect to physical and emotional consequences. The findings show
      that care-giving has detrimental effects on the lives of informal caregivers, and
      that they are in significant need of social support to help them deal with care
      giving tasks and responsibilities. Based on the findings, an integrated social
      support programme is proposed, tailored to the needs of informal caregivers. 

PMID- 24024496
TI  - Competitive sorption of Pb(II) and Zn(II) on polyacrylic acid-coated hydrated
      aluminum-oxide surfaces.
AB  - Natural organic matter (NOM) often forms coatings on minerals. Such coatings are
      expected to affect metal-ion sorption due to abundant sorption sites in NOM and
      potential modifications to mineral surfaces, but such effects are poorly
      understood in complex multicomponent systems. Using poly(acrylic acid) (PAA), a
      simplified analog of NOM containing only carboxylic groups, Pb(II) and Zn(II)
      partitioning between PAA coatings and alpha-Al2O3 (1-102) and (0001) surfaces was
      investigated using long-period X-ray standing wave-florescence yield
      spectroscopy. In the single-metal-ion systems, PAA was the dominant sink for
      Pb(II) and Zn(II) for alpha-Al2O3(1-102) (63% and 69%, respectively, at 0.5 MUM
      metal ions and pH 6.0). In equi-molar mixed-Pb(II)-Zn(II) systems, partitioning
      of both ions onto alpha-Al2O3(1-102) decreased compared with the single-metal-ion
      systems; however, Zn(II) decreased Pb(II) sorption to a greater extent than vice
      versa, suggesting that Zn(II) outcompeted Pb(II) for alpha-Al2O3(1-102) sorption
      sites. In contrast, >99% of both metal ions sorbed to PAA when equi-molar Pb(II)
      and Zn(II) were added simultaneously to PAA/alpha-Al2O3(0001). PAA outcompeted
      both alpha-Al2O3 surfaces for metal sorption but did not alter their intrinsic
      order of reactivity. This study suggests that single-metal-ion sorption results
      cannot be used to predict multimetal-ion sorption at NOM/metal-oxide interfaces
      when NOM is dominated by carboxylic groups. 

PMID- 24024497
TI  - The effects of airway microbiome on corticosteroid responsiveness in asthma.
AB  - RATIONALE: The role of airway microbiome in corticosteroid response in asthma is
      unknown. OBJECTIVES: To examine airway microbiome composition in patients with
      corticosteroid-resistant (CR) asthma and compare it with patients with
      corticosteroid-sensitive (CS) asthma and normal control subjects and explore
      whether bacteria in the airways of subjects with asthma may direct alterations in
      cellular responses to corticosteroids. METHODS: 16S rRNA gene sequencing was
      performed on bronchoalveolar lavage (BAL) samples of 39 subjects with asthma and
      12 healthy control subjects. In subjects with asthma, corticosteroid
      responsiveness was characterized, BAL macrophages were stimulated with pathogenic
      versus commensal microorganisms, and analyzed by real-time polymerase chain
      reaction for the expression of corticosteroid-regulated genes and cellular p38
      mitogen-activated protein kinase (MAPK) activation. MEASUREMENTS AND MAIN
      RESULTS: Of the 39 subjects with asthma, 29 were CR and 10 were CS. BAL
      microbiome from subjects with CR and CS asthma did not differ in richness,
      evenness, diversity, and community composition at the phylum level, but did
      differ at the genus level, with distinct genus expansions in 14 subjects with CR
      asthma. Preincubation of asthmatic airway macrophages with Haemophilus
      parainfluenzae, a uniquely expanded potential pathogen found only in CR asthma
      airways, resulted in p38 MAPK activation, increased IL-8 (P < 0.01), mitogen
      activated kinase phosphatase 1 mRNA (P < 0.01) expression, and inhibition of
      corticosteroid responses (P < 0.05). This was not observed after exposure to
      commensal bacterium Prevotella melaninogenica. Inhibition of transforming growth
      factor-beta-associated kinase-1 (TAK1), upstream activator of MAPK, but not p38
      MAPK restored cellular sensitivity to corticosteroids. CONCLUSIONS: A subset of
      subjects with CR asthma demonstrates airway expansion of specific gram-negative
      bacteria, which trigger TAK1/MAPK activation and induce corticosteroid
      resistance. TAK1 inhibition restored cellular sensitivity to corticosteroids.

PMID- 24024498
TI  - Tonsil surface epithelium is ideal for monitoring Ki-67 immunohistochemical
      staining.
AB  - AIMS: To identify an easily obtainable non-neoplastic tissue that can be used as
      control material for monitoring optimal Ki-67 immunohistochemical staining.
      METHODS AND RESULTS: Various tissues, including tonsil (60), uterine cervix (31),
      breast skin (26), oesophagus (15), stomach (15), small intestine (15) and colon
      (16), were studied in the search for ideal control tissue. Tonsil surface
      epithelium is superior to other tissues because it displayed an easily recognized
      Ki-67 staining pattern including high positive (parabasal layer), low positive
      (intermediate layer) and negative (basal and superficial layers) zones. Moderate
      to weak staining of the majority of the intermediate cells could serve as a
      threshold for positive staining. Of the variables potentially affecting staining
      results that were tested, the pretreatment solution for antigen retrieval had the
      greatest impact, of which pH 9 EDTA was far better than pH 6 citrate solution.
      CONCLUSIONS: Tonsil surface epithelium is a useful control for monitoring Ki-67
      staining. Achieving optimal staining results could minimize variations in Ki-67
      index due to differences in the staining methods used by different laboratories.

PMID- 24024500
TI  - Small molecule inhibitors of human adipocyte fatty acid binding protein (FABP4).
AB  - Fatty acid binding protein 4 (FABP4) is expressed in adipocytes and macrophages,
      and modulates inflammatory and metabolic response. Studies in FABP4-deficient
      mice have shown that this lipid carrier has a significant role within the field
      of metabolic syndrome, inflammation and atherosclerosis; thus, its inhibition may
      open up new opportunities to develop novel therapeutic agents. A number of potent
      small molecule inhibitors of FABP4 have been identified and found to have the
      potential to prevent and treat metabolic diseases such as type-2 diabetes and
      atherosclerosis. Due to the ubiquity of endogenous fatty acids and the high
      intracellular concentration of FABP4, the inhibitors need to have significantly
      greater intrinsic potency than endogenous fatty acids. Furthermore, heart-type
      FABP (FABP3), which is expressed in both heart and skeletal muscle, is involved
      in active fatty acid metabolism where it transports fatty acids from the cell
      membrane to mitochondria for oxidation. However, FABP3 shares high overall
      sequence identity and similar 3D structure with FABP4, but has a potential
      problem with selectivity. In this review, we would like to analyze the main
      inhibitors that have appeared in the literature in the last decade, focusing on
      chemical structures, biological properties, selectivity and structure-activity
      relationships. 

PMID- 24024499
TI  - Glomerular filtration rate estimated using creatinine, cystatin C or both markers
      and the risk of clinical events in HIV-infected individuals.
AB  - OBJECTIVES: The accuracy and precision of glomerular filtration rate (GFR)
      estimating equations based on plasma creatinine (GFR(cr)), cystatin C (GFR(cys))
      and the combination of these markers (GFR(cr-cys)) have recently been assessed in
      HIV-infected individuals. We assessed the associations of GFR, estimated by these
      three equations, with clinical events in HIV-infected individuals. METHODS: We
      compared the associations of baseline GFR(cr), GFR(cys) and GFR(cr-cys) [using
      the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations] with
      mortality, cardiovascular events (CVEs) and opportunistic diseases (ODs) in the
      Strategies for the Management of Antiretroviral Therapy (SMART) study. We used
      Cox proportional hazards models to estimate unadjusted and adjusted hazard ratios
      per standard deviation (SD) change in GFR. RESULTS: A total of 4614 subjects from
      the SMART trial with available baseline creatinine and cystatin C data were
      included in this analysis. Of these, 99 died, 111 had a CVE and 121 had an OD.
      GFR(cys) was weakly to moderately correlated with HIV RNA, CD4 cell count, high
      sensitivity C-reactive protein, interleukin-6, and D-dimer, while GFR(cr) had
      little or no correlation with these factors. GFR(cys) had the strongest
      associations with the three clinical outcomes, followed closely by GFR(cr-cys),
      with GFR(cr) having the weakest associations with clinical outcomes. In a model
      adjusting for demographics, cardiovascular risk factors, HIV-related factors and
      inflammation markers, a 1-SD lower GFR(cys) was associated with a 55% [95%
      confidence interval (CI) 27-90%] increased risk of mortality, a 21% (95% CI 0
      47%) increased risk of CVE, and a 22% (95% CI 0-48%) increased risk of OD.
      CONCLUSIONS: Of the three CKD-EPI GFR equations, GFR(cys) had the strongest
      associations with mortality, CVE and OD.

PMID- 24024501
TI  - The effect of simulation-based crew resource management training on measurable
      teamwork and communication among interprofessional teams caring for postoperative
      patients.
AB  - BACKGROUND: Many adverse events in health care are caused by teamwork and
      communication breakdown. This study was conducted to investigate the effect of a
      point-of-care simulation-based team training curriculum on measurable teamwork
      and communication skills in staff caring for postoperative patients. METHODS:
      Twelve facilities involving 334 perioperative surgical staff underwent simulation
      based training. Pretest and posttest self-report data included the Self-Efficacy
      of Teamwork Competencies Scale. Observational data were captured with the
      Clinical Teamwork Scale. RESULTS: Teamwork scores (measured on a five-point
      Likert scale) improved for all eight survey questions by an average of 18% (3.7
      to 4.4, p < .05). The observed communication rating (scale of 1 to 10) increased
      by 16% (5.6 to 6.4, p < .05). CONCLUSION: Simulation-based team training for
      staff caring for perioperative patients is associated with measurable
      improvements in teamwork and communication.

PMID- 24024502
TI  - Competencies for preceptorship in the Brazilian health care system.
AB  - BACKGROUND: Preceptorship is an emerging component of the Brazilian health care
      system for human resources education. This study attempted to identify
      competencies for preceptorship in this system. METHODS: An exploratory
      descriptive study was conducted with the Delphi technique. The participants were
      primary health care professionals from the South of Brazil who were working in
      nine professional areas, including nursing. The participants had served as
      preceptors in an educational program promoted by the Ministries of Education and
      Health. RESULTS: Forty-three competencies were identified and classified into
      nine domains: education, professional values, basic public health sciences,
      management, health care, teamwork, communication, community orientation, and
      professional development. CONCLUSION: The findings showed that preceptors were
      committed to the education of future health care professionals. The development
      of pedagogical skills was emphasized, as was the necessity of education before
      preceptorship. These competencies constitute a useful reference for continuing
      professional education.

PMID- 24024503
TI  - Bladder buzz: the effect of a 6-week evidence-based staff education program on
      knowledge and attitudes regarding urinary incontinence in a nursing home.
AB  - BACKGROUND: Research shows that there is a basic gap in the knowledge of nursing
      home staff about urinary incontinence and the previous societal belief that
      urinary incontinence is a normal part of aging. This study examines the knowledge
      of nursing home staff about the types and treatment of urinary incontinence as
      well as attitudes toward urinary incontinence. METHODS: A quasi-experimental,
      within-subject, longitudinal pretest/posttest design was used. Nursing home staff
      members received a 6-week educational intervention on the types and treatment of
      urinary incontinence and attitudes toward urinary incontinence. RESULTS: Changes
      in knowledge about the types of urinary incontinence showed statistical
      significance for stress (p < .001), functional (p < .003), and overflow (p < .00)
      urinary incontinence. Changes in attitudes toward urinary incontinence showed
      statistical significance (p < .000). Changes in staff knowledge of the assessment
      and treatment of urinary incontinence did not reach statistical significance.
      CONCLUSION: This study showed that creative, evidence-based educational
      programming can improve staff knowledge about urinary incontinence and change
      staff attitudes toward urinary incontinence. Further research is needed on staff
      knowledge about the assessment and treatment of urinary incontinence.

PMID- 24024504
TI  - Patient navigation in oncology nursing: an innovative blended learning model.
AB  - Nurses are ideally suited to assume professional patient navigation roles in
      cancer care. Continuing education and staff development are essential for nurses
      to implement their roles to the fullest potential. This article describes an
      innovative patient navigation course that was developed to meet the educational
      needs of nurses who work with patients who have been diagnosed with cancer or are
      undergoing evaluation for cancer. Adult learning principles and interactive
      teaching strategies facilitated learning that was relevant and applicable to all
      nurses. Of the 200 participants, 77.5% completed questionnaires before and after
      the course. The questionnaire administered after the course showed a
      statistically significant increase in average total confidence scores on
      knowledge and skills in the seven domains examined (p < .00 to .03). This change
      reflected improvements in overall confidence in key principles and role functions
      of patient navigation. The course provided an opportunity for nurses to enhance
      their individual practice in patient navigation in the following areas: meeting
      patient needs for emotional and supportive care; providing information and
      education; and facilitating coordination and continuity of care.

PMID- 24024505
TI  - Evaluation of the cytotoxic effect of camptothecin solid lipid nanoparticles on
      MCF7 cells.
AB  - Camptothecin (CPT) and its analogs exhibit remarkable anti-tumor activity, due to
      their ability to inhibit DNA topoisomerase I. However, its use is limited by the
      lack of solubility and stability of the active lactone form. An attractive
      alternative is the encapsulation of CPT within liposomes. In this study, CPT was
      incorporated into solid lipid nanoparticles (SLN) based on the triglyceride,
      Compritol 888 ATO, using supercritical fluid technology without requiring the use
      of harmful solvents. This drug delivery system was characterized and its
      cytotoxicity effect was evaluated by measuring MCF7 and MCF10A cell viability as
      a function of drug loading during a 48-h treatment. Results showed that after 10
      h of treatment, MCF7 cells displayed an IC50 of 0.23+/-0.034 MUM at a 1:5
      (CPT:SLN) loading and 0.22+/-0.027 MUM at a 1:10 loading, whereas MCF10A cells
      displayed an IC50 of 0.40+/-0.036 MUM at 1:5 and 0.60+/-0.063 MUM at 1:10. On the
      other hand, the IC50 of free CPT was 0.57+/-0.035 MUM and 1.07+/-0.077 MUM for
      MCF7 and MCF10A cells, respectively. Cellular uptake and retention measurements
      in both cells displayed a two-fold increase when using the SLN formulation. The
      results from this study showed that the cytotoxic effects of CPT in a SLN
      formulation improved when compared with those seen with free CPT. The results of
      this study showed that delivery of CPT as a SLN formulation could be a promising
      strategy for enhancing its chemotherapeutic effects.

PMID- 24024506
TI  - Wet spun microfibers: potential in the design of controlled-release scaffolds?

PMID- 24024507
TI  - Stent-based drug-delivery systems: current challenges and future trends.

PMID- 24024510
TI  - Research spotlight: sirolimus-coated stents for airway tracheal stenosis: a
      future 3D model concept with today's knowledge.
AB  - Currently, interventional pulmonology has the tools for efficient de-bulking of
      tracheal stenosis, which can either be the result of cancer tissue or benign
      tissue growth inside the respiratory tract. There are additionally other
      situations, such as thracheomalece and fistula formation, which require stent
      placement for efficient support in the tract wall. These are situations where the
      placement of a stent is necessary either directly upon diagnosis or after
      interventional treatment. However, a major adverse effect of stent placement is
      the formation or reformation of granuloma tissue and the site of the lesion has
      to be frequently evaluated and treated. In this article we provide insights of
      novel methods for inhibiting the pathways that are activated or deregulated and
      subsequently induce granuloma tissue formation. We also present a future 3D model
      that we are currently constructing in our laboratory from human lung fibroblast
      (adult) in order to evaluate novel local treatment administrations with sirolimus
      biodegradable stents, in order to block or prolong the granuloma tissue
      formation. 

PMID- 24024511
TI  - pH-sensitive liposomes for drug delivery in cancer treatment.
AB  - In recent years, liposomes have been employed with growing success as
      pharmaceutical carriers for antineoplastic drugs. One specific strategy used to
      enhance in vivo liposome-mediated drug delivery is the improvement of
      intracytoplasmic delivery. In this context, pH-sensitive liposomes (pHSLip) have
      been designed to explore the endosomal acidification process, which may lead to a
      destabilization of the liposomes, followed by a release of their contents into
      the cell cytoplasm. This review considers the current status of pHSLip
      development and its applicability in cancer treatment, focusing on the mechanisms
      of pH sensitivity and liposomal composition of pHSLip. The final section will
      discuss the application of these formulations in both in vitro and in vivo
      studies of antitumor efficacy. 

PMID- 24024513
TI  - Soft contact lenses for controlled ocular delivery: 50 years in the making.
AB  - The use of contact lenses as ocular bandages for drug delivery was envisioned
      nearly 50 years ago by Wichterle and co-workers. Despite the therapeutic
      advantages that can be obtained, this application has to face up to the poor
      affinity shown by commercially available contact lenses for most ophthalmic
      drugs, resulting in small amounts of drug being loaded and short time of
      therapeutic levels in the eye structures. Novel strategies that appeared in the
      beginning of 21st century, for example coating lenses with vitamin E,
      incorporation of drug nanocarriers or application of molecular imprinting
      technology, are becoming relevant tools for development of true drug/contact lens
      combination products that may be available for ocular therapy in the foreseeable
      future. 

PMID- 24024512
TI  - Enhancing nucleic acid delivery by photochemical internalization.
AB  - Photochemical internalization (PCI) is a method for releasing macromolecules from
      endosomal and lysosomal compartments. The PCI approach uses a photosensitizer
      that localizes to endosomal and lysosomal compartments, and a light source with
      appropriate light spectra for excitation of the photosensitizer. Upon
      photosensitizer excitation, endosomal and lysosomal membranes are destroyed, due
      to the formation of reactive oxygen species, followed by release of the
      endocytosed material. PCI has been demonstrated to enhance and control (site- and
      time-specific) delivery of various macromolecules such as viruses, proteins,
      chemotherapeutics, nucleic acid, and so on. In this Review we present past and
      current studies of PCI-controlled delivery of natural and artificial nucleic
      acids, such as peptide nucleic acids, siRNA molecules, mRNA molecules and
      plasmids. We also discuss critical aspects to further the possibilities for
      successful gene targeting in space and time. 

PMID- 24024514
TI  - Safety and efficient ex vivo expansion of stem cells using platelet-rich plasma
      technology.
AB  - The goal of this Review is to provide an overview of the cell culture media
      supplements used in the ex vivo expansion of stem cells intended for cell
      therapy. Currently, the gold standard is the culture supplemented with fetal
      bovine serum, however, their use in cell therapy raises many concerns. The
      alternatives to its use are presented, ranging from the use of human serum to
      platelet-rich plasma (PRP), to serum-free media or extracellular matrix
      components. Finally, various growth factors present in PRP are described, which
      make it a safe and effective stem cell expansion supplement. These growth factors
      could be responsible for their efficiency, as they increase both stem cell
      proliferation and survival. The different PRP formulations are also discussed, as
      well as the need for protocol standardization. 

PMID- 24024515
TI  - Metallic nanoparticles and their medicinal potential. Part II: aluminosilicates,
      nanobiomagnets, quantum dots and cochleates.
AB  - Metallic miniaturization techniques have taken metals to nanoscale size where
      they can display fascinating properties and their potential applications in
      medicine. In recent years, metal nanoparticles such as aluminium, silicon, iron,
      cadmium, selenium, indium and calcium, which find their presence in
      aluminosilicates, nanobiomagnets, quantum dots (Q-dots) and cochleates, have
      caught attention of medical industries. The increasing impact of metallic
      nanoparticles in life sciences has significantly advanced the production
      techniques for these nanoparticles. In this Review, the various methods for the
      synthesis of nanoparticles are outlined, followed by their physicochemical
      properties, some recent applications in wound healing, diagnostic imaging,
      biosensing, assay labeling, antimicrobial activity, cancer therapy and drug
      delivery are listed, and finally their toxicological impacts are revised. The
      first half of this article describes the medicinal uses of two noble
      nanoparticles - gold and silver. This Review provides further information on the
      ability of aluminum, silicon, iron, selenium, indium, calcium and zinc to be used
      as nanoparticles in biomedical sciences. Aluminosilicates find their utility in
      wound healing and antibacterial growth. Iron-oxide nanoparticles enhance the
      properties of MRI contrast agents and are also used as biomagnets. Cadmium,
      selenium, tellurium and indium form the core nanostructures of tiny Q-dots used
      in cellular assay labeling, high-resolution cell imaging and biosensing.
      Cochleates have the bivalent nano ions calcium, magnesium or zinc imbedded in
      their structures and are considered to be highly effective agents for drug and
      gene delivery. The aluminosilicates, nanobiomagnets, Q-dots and cochleates are
      discussed in the light of their properties, synthesis and utility. 

PMID- 24024516
TI  - Nanoparticles targeting mechanisms in cancer therapy: current limitations and
      emerging solutions.
AB  - It has been more than one century since Paul Ehrlich spoke about the idea of
      targeting specific molecules in the cell when he coined the 'Magic Bullet'
      principle. In most occasions, we seek new pharmacodynamic models for therapy, but
      nanoparticles provide a chance to modify the already existing pharmacokinetics of
      drugs to meet needed pharmacodynamic models. In the scope of 'nanoscale', every
      entity has different characters, and no general rules control pharmacokinetics of
      nanoparticulate drugs as new physical and physicochemical properties are added to
      equations. However, such remarkable drug models are still quite far from
      achieving their potential in clinical application. Among the major obstacles is
      that most available results in nanoparticles targeting rely upon in vitro and
      animal models that do not match the tumor environment characteristics in humans.
      This Review discusses the concept of targeting tumor cells with nanoparticles,
      the limitations that lead to its incomplete application in clinical practice
      along with some of the promising solutions to such limitations. 

PMID- 24024518
TI  - Epidemiology of primary liver cancer in Serbia and possible connection with
      cyanobacterial blooms.
AB  - Today, the occurrence of harmful cyanobacterial blooms is a common phenomenon and
      a potential global health problem. Cyanobacteria can produce metabolites highly
      toxic to humans. More than 80% of reservoirs used for water supply in Central
      Serbia have bloomed over the past 80 years. A 10-year epidemiological study
      showed a significant increase in the incidence of primary liver cancer (PLC) in
      the regions where water from the blooming reservoirs was used for human
      consumption. At the same time, no correlation was found between the incidence of
      PLC and other risk factors, such as cirrhosis and hepatitis viruses. Given the
      strong association with PLC induction and various known possible mechanisms of
      carcinogenic action, it is highly possible that, cyanotoxins--acting as initiator
      and promoter--may be the major risk factor that acts synergistically with other
      risk factors to cause increased incidence of PLC. However, at present, it is
      still not certain whether cyanotoxins alone were sufficient to induce PLC.
      Therefore, additional assessment of the health risks that may arise from human
      exposure to cyanotoxins is advisable.

PMID- 24024519
TI  - Evaluation of the toxicity forecasting capability of EPA's ToxCast Phase I data:
      can ToxCast in vitro assays predict carcinogenicity?
AB  - Long-term rodent bioassays have played a central role in protecting human health
      from carcinogens; for ethical and practical reasons their use is decreasing
      whereas genotoxicity testing has taken a pivotal role. However, this strategy--as
      presently implemented--is not sensitive enough to detect all genotoxic
      carcinogens, and cannot detect nongenotoxic carcinogens. Among the alternative
      approaches under study there is the ToxCast/Tox21 project. Following a previous
      study from our laboratory, here we present a new, more extensive analysis of
      ToxCast Phase I results, indicating that at the present state-of-art this
      approach is not able to predict the carcinogenicity of chemicals. Possible
      reasons for this mediocre performance are discussed, and opinions on ways to tune
      up the project in the next phases are presented.

PMID- 24024520
TI  - Phototoxicity of herbal plants and herbal products.
AB  - Plants are used by humans in daily life in many different ways, including as
      food, herbal medicines, and cosmetics. Unfortunately, many natural plants and
      their chemical constituents are photocytotoxic and photogenotoxic, and these
      phototoxic phytochemicals are widely present in many different plant families. To
      date, information concerning the phototoxicity and photogenotoxicity of many
      plants and their chemical constituents is limited. In this review, we discuss
      phototoxic plants and their major phototoxic constituents; routes of human
      exposure; phototoxicity of these plants and their constituents; general
      mechanisms of phototoxicity of plants and phototoxic components; and several
      representative phototoxic plants and their photoactive chemical constituents. 

PMID- 24024521
TI  - Nanoneurotoxicity to nanoneuroprotection using biological and computational
      approaches.
AB  - Nanoparticles (NPs) that are ~100 nm in diameter can potentially cause toxicity
      in the central nervous system (CNS). Although NPs exhibit positive aspects, these
      molecules primarily exert negative or harmful effects. Thus, the beneficial and
      harmful effects should be compared. The prevalence of neurodegenerative diseases,
      such as Alzheimer disease, Parkinson disease, and some brain tumors, has
      increased. However, the major cause of these diseases remains unknown. NPs have
      been considered as one of the major potential causes of these diseases,
      penetrating the human body via different pathways. This review summarizes various
      pathways for NP-induced neurotoxicity, suggesting the development of strategies
      for nanoneuroprotection using in silico and biological methods. Studies of
      oxidative stress associated with gene expression analyses provide efficient
      information for understanding neuroinflammation and neurodegeneration associated
      with NPs. The brain is a sensitive and fragile organ, and evolution has developed
      mechanisms to protect it from injury; however, this protection also hinders the
      methods used for therapeutic purposes. Thus, brain and CNS-related diseases that
      are the cause of disability and disorder are the most difficult to treat. There
      are many obstacles to drug delivery in the CNS, such as the blood brain barrier
      and blood tumor barrier. Considering these barriers, we have reviewed the
      strategies available to map NPs using biological techniques. The surface
      adsorption energy of NPs is the basic force driving NP gathering, protein corona
      formation, and many other interactions of NPs within biological systems. These
      interactions can be described using an approach named the biological surface
      adsorption index. A quantitative structural activity relationship study helps to
      understand different protein-protein or protein-ligand interactions. Moreover,
      equilibrium between cerebrovascular permeability is required when a drug is
      transferred via the circulatory system for the therapy of neurodegenerative
      diseases. Various drug delivery approaches, such as chemical drug delivery and
      carrier-mediated drug delivery, have been established to avoid different barriers
      inhibiting CNS penetration by therapeutic substances. Developing an improved
      understanding of drug receptors and the sites of drug action, together with
      advances in medicinal chemistry, will make it possible to design drugs with
      greatly enhanced activity and selectivity; this may result in a significant
      increase in the therapeutic index.

PMID- 24024523
TI  - Evaluation of real-time quantitative PCR as a standard cytogenetic diagnostic
      tool for confirmation of microarray (aCGH) results and determination of
      inheritance.
AB  - AIM: To evaluate the use of real-time quantitative PCR (qPCR) as a diagnostic
      tool for follow up of abnormal microarray (aCGH) results. METHOD: qPCR was
      performed on 207 samples with known aCGH results to detect chromosomal
      abnormality and determine the capability of qPCR. Eighty-four samples were
      processed and the results compared with the original aCGH result and with one or
      more of the alternative follow-up methods: aCGH, fluorescence in situ
      hybridization (FISH), or karyotyping. A separate cohort of 107 samples was used
      to determine critical threshold values for qPCR. A further 16 samples were
      assessed in reproducibility and sensitivity studies. RESULTS: All qPCR findings
      were consistent with the original aCGH results, and qPCR was found to be a
      superior follow-up method compared to FISH and karyotyping. Critical threshold
      values were also determined from this study. CONCLUSION: In this study, qPCR
      analysis identified all copy number changes. qPCR is an accurate, rapid,
      reliable, and inexpensive technique for confirming copy number changes, and for
      determining the inheritance of such abnormalities to aid interpretation of
      results. We also present the critical threshold values required for qPCR as a
      practical tool. This technique has now been successfully implemented as part of
      the clinical diagnostic service within our laboratory.

PMID- 24024525
TI  - High awareness of hepatitis C virus (HCV) but limited knowledge of HCV
      complications among HIV-positive and HIV-negative men who have sex with men.
AB  - Hepatitis C virus (HCV) has emerged as a sexually transmitted infection among HIV
      positive men who have sex with men (MSM) in high-income countries. Little is
      reported about HCV awareness among MSM, although this is essential for developing
      targeted prevention strategies. We, therefore, studied HCV awareness and
      knowledge among HIV-positive and HIV-negative MSM from the Amsterdam Cohort
      Studies (ACS). During two visits, 1 year apart and starting in October 2007, MSM
      from the ACS answered questions regarding HCV awareness, knowledge of HCV
      transmission (7 items), complications (8 items) and sexual risk behaviour. We
      examined the percentage of HCV awareness and correctly answered knowledge items,
      and whether awareness and knowledge improved significantly over time. Using
      logistic regression, we studied whether HIV status and sexual risk behaviour were
      associated with awareness. Seventy percent (312/444) of HIV-negative and 80%
      (74/92) of HIV-positive MSM reported to have ever heard of HCV on the first
      visit. Overall, awareness increased with 9% between the first and second visit (p
      < 0.001). In multivariate analysis the association of group sex with HCV
      awareness was borderline significant (OR 1.49, 95% CI 0.97-2.30). Compared with
      knowledge of transmission routes, knowledge of complications appeared to be
      limited. In the ACS, awareness of HCV is high, particularly among those reporting
      group sex, an important risk factor for HCV transmission. The majority of
      participants had good knowledge of transmission routes, but limited knowledge of
      complications of chronic HCV infection. HCV prevention messages could be
      strengthened, therefore, by further addressing the complications of HCV
      infection. 

PMID- 24024527
TI  - Synthesis and dual D2 and 5-HT1A receptor binding affinities of 7-piperazinyl and
      7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones.
AB  - A series of new 7-piperazinyl and 7-piperidinyl-3,4-dihydroquinazolin-2(1H)-ones
      has been synthesized. The described compounds are structurally related to
      adoprazine, a potential atypical antipsychotic bearing potent D2 receptor
      antagonist and 5-HT1A receptor agonist properties. Suitably modified aryl
      bromides were prepared and condensed with tert-butyl piperazine-1-carboxylate to
      afford the advanced intermediate piperazinyl-3,4-dihydroquinazolin-2(1H)-one.
      Likewise Suzuki-Miyaura cross-coupling reaction of cyclic vinyl boronate with
      appropriate aryl bromides rendered piperidinyl-3,4-dihydroquinazolin-2(1H)-one.
      The reductive amination of the piperazinyl and piperidinyl-3,4- dihydroquinazolin
      2(1H)-ones with suitably designed biarylaldehydes accomplished the synthesis of
      these title compounds. The described compounds were screened for D2 and 5-HT1A
      receptors binding affinities. The structure-activity relationship studies
      revealed that cyclopentenylpyridine and cyclopentenylbenzyl groups contribute
      significantly to the dual D2 and 5-HT1A receptor binding affinities of these
      compounds. 

PMID- 24024526
TI  - Non-minor injuries among children sustained in an outdoor environment--a
      retrospective register study.
AB  - The aim was to investigate non-minor injuries sustained during outdoor activities
      among 0-12 year old children and to explore self-reported circumstances
      surrounding these incidents. During 2007-2009, the Umea University Hospital
      injury database (IDB) registered 795 children with moderate (n = 778) and serious
      (n = 17) injuries, such as fractures. The IDB includes data from a questionnaire
      completed in the emergency department by the injured child or a parent. The open
      ended questions catch the injured child's description of what circumstances
      precede the injury incident. The most commonly reported activities contributing
      to injuries were play, sport, and transport. Surface impacts were also reported
      as contributing factors along with products such as trampolines, bicycles, and
      downhill skis. By achieving a deeper knowledge about the activities and
      circumstances that precede non-minor injury incidents, creating safer outdoor
      environments may be feasible. 

PMID- 24024528
TI  - Etiology of homosexuality and attitudes toward same-sex parenting: a randomized
      study.
AB  - Attribution theory suggests the hypothesis that heterosexuals' attitudes toward
      homosexual sexual orientation will be more negative when homosexuality is
      attributed to controllable causes. Our randomized study analyzed (a) whether
      beliefs about the genetic or environmental etiology of the homosexual sexual
      orientation can be immediately modified by reading a text and (b) the causal
      effect of attributions about the controllability (environmental etiology) or
      noncontrollability (genetic etiology) of homosexual sexual orientation on the
      rejection of same-sex parenting and their social rights. The sample was composed
      of 190 Spanish university students with a mean age of 22.07 years (SD = 8.46).
      The results show that beliefs about the etiology of the sexual orientation could
      be modified by means of a written text. Furthermore, participants who believed
      that sexual orientation had a genetic etiology showed greater support for social
      rights and less rejection of same-sex parenting. However, the effects were
      detected only when there was a traditional opposition to the family with same-sex
      parenting. When the opposition was normative, the effect was not statistically
      significant. Our results can be useful in planning variables for intervention
      programs designed to foster tolerance toward and normality of sexual diversity. 

PMID- 24024524
TI  - Chronic lung disease in the preterm infant. Lessons learned from animal models.
AB  - Neonatal chronic lung disease, also known as bronchopulmonary dysplasia (BPD), is
      the most common complication of premature birth, affecting up to 30% of very low
      birth weight infants. Improved medical care has allowed for the survival of the
      most premature infants and has significantly changed the pathology of BPD from a
      disease marked by severe lung injury to the "new" form characterized by alveolar
      hypoplasia and impaired vascular development. However, increased patient survival
      has led to a paucity of pathologic specimens available from infants with BPD.
      This, combined with the lack of a system to model alveolarization in vitro, has
      resulted in a great need for animal models that mimic key features of the
      disease. To this end, a number of animal models have been created by exposing the
      immature lung to injuries induced by hyperoxia, mechanical stretch, and
      inflammation and most recently by the genetic modification of mice. These animal
      studies have 1) allowed insight into the mechanisms that determine alveolar
      growth, 2) delineated factors central to the pathogenesis of neonatal chronic
      lung disease, and 3) informed the development of new therapies. In this review,
      we summarize the key findings and limitations of the most common animal models of
      BPD and discuss how knowledge obtained from these studies has informed clinical
      care. Future studies should aim to provide a more complete understanding of the
      pathways that preserve and repair alveolar growth during injury, which might be
      translated into novel strategies to treat lung diseases in infants and adults. 

PMID- 24024530
TI  - Assessing the effect of introducing a permitted phase through the use of flashing
      yellow arrow signal for left-turning vehicles.
AB  - This paper evaluates the direct and indirect effects of introducing a permitted
      phase, through the use of flashing yellow arrow (FYA) signal for left-turning
      vehicles, in reducing crashes at intersections. Data for 18 study intersections
      in the city of Charlotte, NC, USA were used to conduct a before-after comparison
      study through the use of Empirical Bayes (EB) method and examine the effects. The
      estimated number of left-turn crashes, had the FYA signal not been installed, was
      compared to the actual number of left-turn crashes to assess the direct effect,
      while the estimated total number of crashes, had the FYA signal not been
      installed, was compared to the actual total number of crashes to assess the
      indirect effect. Only left-turn crashes along a selected FYA leg were used to
      examine the direct effect as the number of legs (approaches) with the FYA signal
      varied between the selected study intersections. The results obtained indicate
      that the FYA signal helps reduce the left-turn crashes (direct effect). It does
      not lead to any negative consequences. Instead, the FYA signal has the potential
      to indirectly lower the total number of crashes (indirect effect) and contribute
      to improved safety at intersections. 

PMID- 24024529
TI  - Experimental human exposure to air pollutants is essential to understand adverse
      health effects.
AB  - Air pollution has been found to cause significant global mortality, with 6.8
      million excess deaths attributed to air pollution each year, and similarly large
      numbers of exacerbations of asthma, chronic obstructive pulmonary disease, and
      cardiovascular diseases. Epidemiological research has identified associations,
      and experimental human exposure has provided critical information on dose
      response relationships of adverse effects caused by controlled human exposure to
      individual pollutants. Human exposures further enable examination of the
      relationship of adverse effects such as symptoms and pulmonary function changes
      to presumed mechanisms of disease revealed through analysis of bronchoalveolar
      lavage fluid obtained from the lower respiratory tract. In this Perspective, we
      analyze the ethics of human exposure, the importance of the information gained,
      and the risks of such exposure. We find that these studies appear to have been
      done with proper approval of institutional review boards, were done with informed
      consent from the participants, and have rarely been associated with serious
      adverse events.

PMID- 24024531
TI  - A prospective study of physician pre-hospital anaesthesia in trauma patients:
      oesophageal intubation, gross airway contamination and the 'quick look' airway
      assessment.
AB  - BACKGROUND: In trauma patients intubated in a physician-led pre-hospital trauma
      service we prospectively examined the rate of misplaced tracheal tubes, the
      presence and nature of gross airway contamination, and the value of 'quick look'
      airway assessment to identify patients with subsequent difficult laryngoscopy.
      METHODS: Patients requiring pre-hospital intubation in a 16 month period were
      included. Intubation success rate, misplaced tracheal tube rate, Cormack and
      Lehane grade, and the presence and nature of gross airway contamination were
      recorded at laryngoscopy. Tube placement was verified with carbon dioxide
      detection and chest x-ray. After visual assessment physicians stated whether
      laryngoscopy was expected to be a straightforward or 'difficult'. The assessment
      was compared to subsequent laryngoscopy grade. RESULTS: 400 patients had
      attempted intubation and 399 were successfully intubated. 42 were in cardiac
      arrest and intubated without drugs. There were no oesophageal or misplaced
      tracheal tubes. Gross airway contamination was reported in 177 of 400 patients
      (44%), of which 3/4 was from the upper airway. Unconscious patients had higher
      contamination rates (57%) than conscious patients (34%) (p <= 0.0001). As a test
      of difficult intubation, the 'quick look' generated sensitivity 0.597 and
      specificity 0.763 (PPV and NPV were 0.336 and 0.904 respectively). CONCLUSION:
      This study suggests that when physicians perform pre-hospital anaesthesia they
      have high intubation success rates and the use of ETCO2 monitoring reduces or
      eliminates undetected misplaced tracheal tubes. We found high rates of airway
      contamination; mostly blood from the upper airway. The 'quick look' airway
      assessment had some utility but is unreliable in isolation.

PMID- 24024532
TI  - The bidirectional relationship between body mass index and treatment outcome in
      adolescents with treatment-resistant depression.
AB  - OBJECTIVE: Depression and obesity are associated, but the impact of obesity on
      depression treatment outcome, or, conversely, the impact of treatment on body
      mass index (BMI) in depressed adolescents has not been reported. In this article,
      we examine the bidirectional relationships between BMI and treatment response in
      adolescents with treatment-resistant depression. METHOD: Participants in the
      Treatment of Selective Serotonin Reuptake Inhibitor (SSRI) Resistant Depression
      in Adolescents (TORDIA) study had height and weight assessed at baseline, weekly
      for the first 6 weeks, biweekly for the next 6 weeks, and monthly from weeks 12
      through 24. The impact of baseline BMI as a predictor and moderator of treatment
      response was assessed. In addition, participants' changes in BMI were assessed as
      a function of specific treatment assignment and treatment response. RESULTS:
      Participants assigned to SSRIs had a greater increase in BMI-for-age-sex z-score
      and weight than did those assigned to venlafaxine. Post-hoc, those treated with
      paroxetine or citalopram had the biggest increases in BMI, relative to fluoxetine
      or venlafaxine. Overweight or obesity was neither a predictor nor a moderator of
      treatment outcome, nor of subsequent BMI change. CONCLUSIONS: Overweight status
      does not appear to affect treatment response in adolescents with resistant
      depression. The successful treatment of depression does not appear to favorably
      affect weight or BMI. Fluoxetine and venlafaxine are less likely to cause an
      increase in BMI than paroxetine or citalopram.

PMID- 24024533
TI  - Chronic fluoxetine treatment changes S100B expression during postnatal rat brain
      development.
AB  - BACKGROUND: Fluoxetine, a selective serotonin reuptake inhibitor, is approved for
      treatment of childhood depression. In rats, fluoxetine influences neuronal
      development, but it is unclear whether it also influences glia development. S100B
      is a glia-derived calcium-binding protein, which may influence the development of
      serotonergic fibers and, vice versa, serotonin may influence the expression of
      S100B. OBJECTIVES: The purpose of this study was to investigate whether
      fluoxetine treatment influences the expression of S100B during postnatal
      development, and whether potential changes are regionally dependent upon the time
      frame of drug administration. METHODS: S100B gene expression and S100B protein
      expression in three different brain regions (frontal cortex, hippocampus, and
      striatum) were studied by real-time polymerase chain reaction (PCR) and
      immunohistochemistry, respectively. First, a short-term effect, 24 hours after a
      14 day fluoxetine treatment (5 mg/kg/bw s.c.) of rats either from postnatal day
      (PD) 1 to 15, 21 to 35, or 50 to 64, was investigated. Then, the same treatment
      was used to analyze S100B gene and protein levels at PD 90 (long-term effect).
      RESULTS: At PD 90, a significant increase of gene and protein expression was
      observed in all regions if rats were treated during PDs 21-35, whereas treatment
      during other periods had no long-term effects. A short-term effect 24 hours after
      fluoxetine treatment was found for almost all development stages and regions,
      demonstrated by a significant increase of S100B. CONCLUSIONS: These results
      support recent research indicating a highly drug-sensitive period (i.e.,
      periadolescence) of rat brain development. Therefore, further clinical studies
      should be performed to clarify whether such a sensitive period also exists in
      children.

PMID- 24024535
TI  - Psychopharmacologic treatment of refractory pediatric obsessive compulsive
      disorder.

PMID- 24024534
TI  - Safety, tolerability, and efficacy of quetiapine in youth with schizophrenia or
      bipolar I disorder: a 26-week, open-label, continuation study.
AB  - OBJECTIVE: The purpose of this study was to describe the safety, tolerability,
      and efficacy of quetiapine monotherapy continued for up to 26-weeks in youth with
      schizophrenia or bipolar I disorder. METHODS: Medically healthy boys and girls
      with a baseline Diagnostic and Statistical Manual of Mental Disorders, 4th ed.
      (DSM-IV-TR) diagnosis of schizophrenia (ages 13-17 years) or a manic episode of
      bipolar I disorder (ages 10-17 years) who participated in one of two acute,
      double-blind, placebo-controlled studies of immediate-release quetiapine were
      potentially eligible to enroll in a 26-week, open-label study. During the open
      label study, quetiapine was flexibly dosed at 400-800 mg/day, with options to
      reduce dosing to 200 mg/day based on tolerability. Safety and tolerability
      outcomes assessed from open-label baseline to week 26 included adverse events
      (AEs), metabolic/laboratory parameters, extrapyramidal symptoms, suicidality, and
      vital signs. RESULTS: Of 381 patients enrolled in the open-label study (n=176,
      schizophrenia; n=205, bipolar disorder diagnosis), 237 patients (62.2%) completed
      the 26-week study period (71.0%, schizophrenia; 54.6%, bipolar disorder). The
      most common AEs reported during the study included somnolence, headache,
      sedation, weight increase, and vomiting. A total of 14.9% of patients experienced
      a shift to potentially clinically significant low levels of high-density
      lipoprotein cholesterol and 10.2% of patients experienced a shift to potentially
      clinically significant high triglyceride levels. Weight gain >= 7% was reported
      in 35.6% of patients between open-label baseline and final visit. After
      adjustment for normal growth, 18.3% of study participants experienced clinically
      significant weight gain (i.e., increase in body mass index >= 0.5 standard
      deviations from baseline). CONCLUSIONS: In this 26-week study, quetiapine
      flexibly dosed at 400-800 mg/day, with options to reduce dosing based on
      tolerability, was generally safe and well tolerated in youth. Clinicians should
      monitor lipid profiles and weight gain in youth with schizophrenia or bipolar
      disorder during treatment with quetiapine.

PMID- 24024536
TI  - Manic symptoms as a symptom of antidepressant discontinuation syndrome in a
      child.

PMID- 24024537
TI  - Elevated liver enzymes associated with fluphenazine used to manage delirium
      symptoms in infants.

PMID- 24024539
TI  - Applying the World Report on Disability to children's communication.
AB  - PURPOSE: The World Report on Disability is an important milestone in the
      recognition of people with disabilities; however, the Report acknowledges that
      people with communication difficulties may be underrepresented in estimates of
      disability. Consequently, this article applies the nine recommendations from the
      World Report on Disability to supporting children's communication skills. METHOD:
      Australia is similar to most Minority World countries since it places high regard
      on articulate and literate communication. Recent large-scale Australian studies
      of children with speech, language and communication needs were reviewed to
      determine prevalence, impact and associated environmental and personal factors.
      Studies of met and unmet need were reviewed and discussed in relation to
      legislation and policies. RESULTS: Recent years have seen improvements in the
      collection of and access to disability data about children's communication,
      including the involvement of children in research about the impact of
      communication difficulties on their lives. The prevalence of speech and language
      impairment in children is high and is associated with poorer educational and
      social outcomes at school-age. Significant unmet need for services was noted, and
      there were differences in health, education and disability policies regarding
      access to services. CONCLUSIONS: Updated legislation, policies and practices are
      needed to more effectively support access to services to support children's
      communication across health, education and disability sectors. Implications for
      Rehabilitation There is a high prevalence of speech and language impairment in
      Australian children. Childhood speech and language impairment (and associated
      communication disability) can impact educational, social, behavioural and
      occupational outcomes throughout life. Many Australian children do not have
      sufficient access to targeted services (including speech-language pathology) to
      ameliorate the impact of their communication disability. Formulation of a
      national strategy to support children children's communication is required.

PMID- 24024540
TI  - Monitoring of body position and motion in children with severe cerebral palsy for
      24 hours.
AB  - PURPOSE: To investigate differences in position and body movements between
      children with severe cerebral palsy (CP) and children with typical development
      (TD) during the daytime and while asleep at night. METHOD: Fifteen children with
      severe quadriplegic CP living at home (GMFCS level V, 7 males, 8 females; mean
      age 8 years 3 months; range 3-20 years) and 15 children with TD (6 males, 9
      females; mean age 8 years 7 months; range 1-16 years) participated. Body position
      and movements were recorded for 24 h by a body position monitor and a physical
      activity monitor, respectively. The amount of time spent in one position and the
      durations of inactive periods during the daytime and during night-time sleep were
      computed and analyzed for group differences. RESULTS: In children with CP, the
      mean longest time spent in one position was longer than that in children with TD
      during night-time sleep (5.6 +/- 3.5 h versus 1.6 +/- 1.2 h). In contrast, no
      significant differences were found between the groups during the daytime (1.9 +/-
      1.1 h versus 1.6 +/- 0.7 h). The mean longest time the body remained inactive was
      longer in the children with CP during both daytime and nighttime sleep (0.6 +/-
      0.3 h versus 0.3 +/- 0.3 h for daytime, 1.4 +/- 0.8 h versus 0.7 +/- 0.3 h for
      nighttime). CONCLUSION: Children with severe CP living at home showed prolonged
      immobilized posture during night-time sleep when their caregivers would be likely
      to also be asleep. This may suggest that these children should receive postural
      care assistance at night.

PMID- 24024541
TI  - Under-recognition and under-treatment of DSM-IV classified mood and anxiety
      disorders among disability claimants.
AB  - PURPOSE: This study aimed to examine under-recognition, under-treatment and
      severity of under-treated DSM-IV mood and anxiety disorders among disability
      claimants. METHODS: In a representative sample of Dutch disability claimants (n =
      346), registry codes certified according to the International Classification of
      Diseases 10th edition (ICD-10) by insurance physicians, were compared with
      classifications according to the Diagnostic Statistical Manual of Mental
      Disorders (DSM-IV) detected by the Composite International Diagnostic Interview
      (CIDI). Levels of ICD-10/DSM-IV agreement were assessed for mood and anxiety
      disorders in the total sample, and prevalence of recent DSM-IV mood and anxiety
      disorders in a pure ICD-10 somatic subgroup. Treatment and severity of under
      treated DSM-IV mood and anxiety disorders were assessed in two subgroups of
      disability claimants with either an ICD-10 somatic or mental disorder as primary
      cause of disability, irrespective of any ICD-10 comorbidity. RESULTS: Levels of
      ICD-10/DSM-IV agreement were poor (kappa: 0.237 for mood and 0.260 for anxiety
      disorders). In the pure ICD-10 somatic subgroup, the prevalence of DSM-IV mood
      and anxiety disorders was 3.8% and 11.4%, respectively. In the ICD-10 somatic
      subgroup irrespective of any ICD-10 comorbidity, 45.2% (major depressive
      disorder), 80.0% (social phobia) and 53.3% (general anxiety disorder) were under
      treated. In the ICD-10 mental subgroup, these percentages were 44.7%, 80.9% and
      33.4%, respectively. In both of these subgroups, under-treated DSM-IV mood and
      anxiety disorders were predominantly serious in terms of impairment and
      disability. CONCLUSIONS: Serious mental disorders were found to be substantially
      under-diagnosed and under-treated among disability claimants. To optimize
      diagnosis and treatment of disabling mental disorder, medical professionals in
      insurance, occupational and in the health care sector should closely collaborate.
      For claimants with under-treated mental disorders, tailor-made multidisciplinary
      interventions are needed to promote return to work and to prevent permanent
      disability.

PMID- 24024538
TI  - Attention-deficit/hyperactivity disorder drugs and growth: an Italian prospective
      observational study.
AB  - OBJECTIVE: This study was conducted to assess the long-term effect of
      methylphenidate (MPH) or atomoxetine (ATX) on growth in attention
      deficit/hyperactivity disorder (ADHD) drug-naive children. DESIGN: The study was
      an observational, post-marketing, fourth phase study. METHODS: Data on height and
      weight were collected at baseline and every 6 months up to 24 months. RESULTS:
      Both ATX and MPH lead to decreased height gain (assessed by means of z-scores);
      the effect was significantly higher for ATX than for MPH. At any time, height z
      score decrease in the ATX group was higher than the corresponding decrease
      observed in the MPH group, but the difference was significantly relevant only
      during the first year of treatment. An increment of average weight was observed
      both in patients treated with MPH and in those treated with ATX. However, using
      Tanner's percentile, a subset of patients showed a degree of growth lower than
      expected. This negative effect was significantly higher for ATX than for MPH.
      CONCLUSIONS: We conclude that ADHD drugs show a negative effect on linear growth
      in children in middle term. Such effect appears more evident for ATX than for
      MPH.

PMID- 24024542
TI  - Expectations of rehabilitation following lower limb amputation: a qualitative
      study.
AB  - PURPOSE: To explore the expectations of patients about to undergo prosthetic
      rehabilitation following a lower limb amputation. METHOD:  DESIGN: Qualitative
      study using semi structured interviews. SETTING: Interviews were conducted at two
      district general hospitals. PARTICIPANTS: Eight patients who had undergone a
      major lower limb amputation due to vascular insufficiency were interviewed within
      two weeks of their amputation. All patients had been referred for prosthetic
      rehabilitation. RESULTS: Five key themes emerged from the interviews:
      uncertainty, expectations in relation to the rehabilitation service, personal
      challenges, the prosthesis and returning to normality. These findings illustrate
      how participants faced uncertainty both pre- and postoperatively and often looked
      towards established amputees for the provision of accurate information.
      CONCLUSIONS: As no previous research has specifically explored patients'
      expectations following an amputation, this study adds valuable insight into the
      patient experience. Patient expectations following lower limb amputation appeared
      to be vague and uninformed which may lead to uncertainty and passivity. It was
      found that patients did not know what to expect in relation to the rehabilitation
      process. They expected to return to a normal life following an amputation and
      this expectation appeared to be an important coping mechanism. Patient
      information and discussions should form an important part of the rehabilitation
      process before as well as during prosthetic rehabilitation, to help shape
      realistic expectations. This will allow patients to take a more active, informed
      role in the process. Psychoeducation interventions (talking) appears to be as
      important as "walking" within prosthetic rehabilitation services.

PMID- 24024543
TI  - Exploring expressivity and emotion with artificial voice and speech technologies.
AB  - Emotion in audio-voice signals, as synthesized by text-to-speech (TTS)
      technologies, was investigated to formulate a theory of expression for user
      interface design. Emotional parameters were specified with markup tags, and the
      resulting audio was further modulated with post-processing techniques. Software
      was then developed to link a selected TTS synthesizer with an automatic speech
      recognition (ASR) engine, producing a chatbot that could speak and listen. Using
      these two artificial voice subsystems, investigators explored both artistic and
      psychological implications of artificial speech emotion. Goals of the
      investigation were interdisciplinary, with interest in musical composition,
      augmentative and alternative communication (AAC), commercial voice announcement
      applications, human-computer interaction (HCI), and artificial intelligence (AI).
      The work-in-progress points towards an emerging interdisciplinary ontology for
      artificial voices. As one study output, HCI tools are proposed for future
      collaboration.

PMID- 24024544
TI  - Mutation of Trp(93) of MauG to tyrosine causes loss of bound Ca(2+) and alters
      the kinetic mechanism of tryptophan tryptophylquinone cofactor biosynthesis.
AB  - The dihaem enzyme MauG catalyses a six-electron oxidation required for post
      translational modification of preMADH (precursor of methylamine dehydrogenase) to
      complete the biosynthesis of its TTQ (tryptophan tryptophylquinone) cofactor.
      Trp93 of MauG is positioned midway between its two haems, and in close proximity
      to a Ca2+ that is critical for MauG function. Mutation of Trp93 to tyrosine
      caused loss of bound Ca2+ and changes in spectral features similar to those
      observed after removal of Ca2+ from WT (wild-type) MauG. However, whereas Ca2+
      depleted WT MauG is inactive, W93Y MauG exhibited TTQ biosynthesis activity. The
      rate of TTQ biosynthesis from preMADH was much lower than that of WT MauG and
      exhibited highly unusual kinetic behaviour. The steady-state reaction exhibited a
      long lag phase, the duration of which was dependent on the concentration of
      preMADH. The accumulation of reaction intermediates, including a diradical
      species of preMADH and quinol MADH (methylamine dehydrogenase), was detected
      during this pre-steady-state phase. In contrast, steady-state oxidation of quinol
      MADH to TTQ, the final step of TTQ biosynthesis, exhibited no lag phase. A
      kinetic model is presented to explain the long pre-steady-state phase of the
      reaction of W93Y MauG, and the role of this conserved tryptophan residue in MauG
      and related dihaem enzymes is discussed. 

PMID- 24024545
TI  - Synthesis and application of photolithographically patternable deep blue emitting
      poly(3,6-dimethoxy-9,9-dialkylsilafluorene)s.
AB  - Poly(silafluorene)s (PSFs) are promising light-emitting materials with brilliant
      solid-state blue luminescence, high quantum efficiency, excellent solubility, and
      improved thermal and chemical stability. PSFs are reported to have high electron
      affinity and conductivity originating from sigma*-pi* conjugation between the
      sigma*-antibonding orbital of the exocyclic Si-C bond and the pi* antibonding
      orbital of the butadiene fragment, a promising characteristic for improved charge
      carrier balance in OLEDs. In this paper, we present a protocol for
      photopatterning derivatives of poly(3,6-dimethoxy-9,9-dialkylsilafluorenes) with
      resolutions exceeding 10 MUm. The procedure begins by converting polymers (Mn =
      50-55 kg/mol, PDI = 1.8) with cyclohexenyl and norbornenyl containing side chains
      to their respective epoxides using the Prilezhaev reaction and m
      chloroperoxybenzoic acid (m-CPBA). Using the I-line (365 nm) of a Karl Suss MA6
      mask aligner, a 1 s UV light exposure of the photoacid generator (PAG) bis(4-tert
      butylphenyl)iodonium hexafluoro-phosphate (DtBPI-PF6) generates sufficient
      protons to catalyze epoxide ring-opening and form a bridging network of covalent
      C-O bonds which renders the material insoluble in developing solvents such as
      toluene or THF. The resultant cross-linked material possess characteristic blue
      photoluminescence with solid state quantum yields >80%. Polymer films have
      excellent transparency (with a measured Eg ~ 3.0 eV). Energy levels determined
      using cyclic voltammetry were -5.7 and -2.7 eV for HOMO and LUMO, respectively.
      Additionally, several device applications are demonstrated which incorporate
      cross-linked films. These include examples of solid state lasing in the region of
      420-450 nm from cross-linked films on second order corrugated silica substrates
      (Lambda = 200 nm). OLEDs were also prepared with a cross-linked emitting layer as
      part of a trilayer device which we report to have a maximum external quantum
      efficiency of 3.2% at 33 mA/cm(2) and a stable blue-violet emission with an
      electroluminescence maximum at 410 nm. Photopatternable PSF epoxides are also
      shown to be efficient hosts for Forster energy transfer and we provide examples
      of pattern layers incorporating small molecule emitters which emit in both the
      red and green while blue emission of the host is effectively suppressed. 

PMID- 24024546
TI  - Sexual education, gender ideology, and youth sexual empowerment.
AB  - Sexual education plays an essential role in preventing unplanned pregnancy and
      the transmission of sexually transmitted infections (STIs). School-based sexual
      education programs, in particular, may be well positioned to address social
      factors that are empirically linked to negative sexual health outcomes, such as
      traditional social norms surrounding gender and sexuality. However, youth are
      seldom granted access to sexual education programs that explicitly address these
      issues. This study presents findings from a pretest-posttest survey of a sexual
      education program that did. It was designed for eighth graders (N=95) in the
      context of a school-community collaboration. The study assessed the links between
      several components of sexual empowerment, including gender ideology, sexual
      knowledge, and contraceptive beliefs. Findings link participation in the sexual
      education program to more progressive attitudes toward girls and women, less
      agreement with hegemonic masculinity ideology, and increases in sexual health and
      resource knowledge. Structural equation models suggest that traditional attitudes
      toward women were significantly related to hegemonic masculinity ideology among
      both boys and girls, which was in turn negatively related to safer contraceptive
      beliefs. 

PMID- 24024548
TI  - Water safety and drowning prevention.

PMID- 24024547
TI  - Quantitative analyses of ribulose-1,5-bisphosphate carboxylase/oxygenase
      (RubisCO) large-subunit genes (cbbL) in typical paddy soils.
AB  - The Calvin cycle is known to be the major pathway for CO2 fixation, but our
      current understanding of its occurrence and importance in paddy soils is poor. In
      this study, the diversity of three ribulose-1,5-bisphosphate
      carboxylase/oxygenase large-subunit genes (cbbLG, cbbLR, cbbM) was investigated
      by clone library, T-RFLP, qPCR, and enzyme assay in five paddy soils in China.
      The cbbLG sequences revealed a relatively low level of diversity and were mostly
      related to the sequences of species from Thiobacillus. In contrast, highly
      diverse cbbLR and cbbM sequences were dispersed on the phylogenetic trees, and
      most of them were distantly related to known sequences, even forming separate
      clusters. Abundances of three cbbL genes ranged from 10(6) to 10(9) copies g(-1)
      soil, and cbbLR outnumbered cbbM and cbbLG in all soil samples, indicating that
      cbbLR may play a more important role than other two cbbL genes. Soil properties
      significantly influenced cbbL diversity in five paddy soils, of which clay
      content, C/N ratio, CEC, pH, and SOC correlated well with variations in microbial
      composition and abundance. In summary, this study provided a comparison of three
      cbbL genes, advancing our understanding of their role in carbon sequestration and
      nutrient turnover in the paddy soil.

PMID- 24024549
TI  - Before-after paired data.

PMID- 24024550
TI  - Altered relationship between R-R interval and R-R interval variability in
      endurance athletes with overtraining syndrome.
AB  - Autonomic dysfunction decreases within-subject correlation between R-R interval
      length (RRi) and vagally mediated RRi variability in cardiac disease. We tested
      the hypothesis that overtraining syndrome (OTS) may also weaken this
      relationship. Nine OTS and 10 control endurance athletes underwent 24-h
      electrocardiogram monitoring, which was repeated in eight OTS and nine control
      athletes after 6 months, when two OTS athletes still had symptoms of OTS. The
      power of high-frequency (HF) oscillations of RRi was analyzed in 5-min epochs
      over the whole recording. Quadratic regression was performed between 5-min values
      of RRi and log-transformed (ln) HF to obtain R(2) for each recording. The
      relationship between RRi and HFln was higher in the OTS athletes than controls
      [R(2): 0.87 (90% confidence interval, CI: 0.84-0.89) vs 0.78 (90% CI: 0.72-0.84);
      P = 0.034; effect size = 1.22]. Large decrease in R(2) was observed in six
      recovered OTS athletes after 6 months follow-up [DeltaR(2): -0.12 (90% CI: -0.25
      0.01); P = 0.11; effect size = 1.44] with no changes in the controls. Mean values
      of RRi and its variability did not differ between the groups. The within-subject
      correlation between RRi and vagally mediated RRi variability was stronger in
      endurance athletes with OTS compared with controls. The present findings may
      improve the detection of OTS and recovery from OTS in endurance athletes.

PMID- 24024551
TI  - The impact of safety and quality of health care on Chinese nursing career
      decision-making.
AB  - AIM: The aim of the study was to understand why nurses leave nursing practice in
      China by exploring the process from recruitment to final exit. This report
      examines the impact of safety and quality of health care on nursing career
      decision-making from the leavers' perspective. BACKGROUND: The nursing shortage
      in China is more serious than in most developed countries, but the loss of nurses
      through voluntarily leaving nursing practice has not attracted much attention.
      METHOD: This qualitative study draws on a grounded theory approach. In-depth
      interviews with 19 nurses who have left nursing practice and were theoretically
      sampled from one provincial capital city in Mainland China. FINDING: 'Loss of
      confidence in the safety and quality of health care' became one of the main
      categories from all leavers' accounts of their decision to leave nursing
      practice. It emerged from three themes 'Perceiving risk in clinical practice',
      'Recognising organisational barriers to safety' and 'Failing to meet expectations
      of patients'. DISCUSSION: The findings indicate that the essential work value of
      nursing to the leavers is the safety and quality of care for their patients. When
      nurses perceived that they could not fulfil this essential work value in their
      nursing practice, some of them could not accept the compromise to their value of
      nursing and left voluntarily to get away from the physical and mental stress.
      However, some nurses had to stay and accept the limitations on the safety and
      quality of health care. CONCLUSION: The study suggests that well-qualified nurses
      voluntarily leaving nursing practice is a danger signal for patients and
      hospitals, and has caused deterioration in nursing morale for both current and
      potential nursing workforces. It suggests that safety and quality of health care
      could be improved when individual nurses are empowered to exercise nursing
      autonomy with organisational and managerial support. IMPLICATIONS FOR NURSING
      MANAGEMENT: The priority retention strategies need to remove organisational
      barriers to the safety and quality of health care. Under the current nursing
      shortage, Chinese hospital managers might consider recruiting nurses and care
      assistants of different educational levels, which would effectively improve
      nursing team work and support nurses' to stay and actively achieve their work
      values for the safety and quality of health care.

PMID- 24024553
TI  - A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3
      in autosomal recessive microphthalmia.
AB  - Anomalies of eye development can lead to the rare eye malformations
      microphthalmia and anophthalmia (small or absent ocular globes), which are
      genetically very heterogeneous. Several genes have been associated with
      microphthalmia and anophthalmia, and exome sequencing has contributed to the
      identification of new genes. Very recently, homozygous variations within ALDH1A3
      have been associated with autosomal recessive microphthalmia with or without
      cysts or coloboma, and with variable subphenotypes of developmental delay/autism
      spectrum disorder in eight families. In a consanguineous family where three of
      the five siblings were affected with microphthalmia/coloboma, we identified a
      novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the
      three affected siblings, one had intellectual disability and one had intellectual
      disability and autism, while the last one presented with normal development. This
      study contributes further to the description of the clinical spectrum associated
      with ALDH1A3 mutations, and illustrates the interfamilial clinical variation
      observed in individuals with ALDH1A3 mutations. 

PMID- 24024552
TI  - Essential role of the molecular chaperone gp96 in regulating melanogenesis.
AB  - Through a process known as melanogenesis, melanocyte produces melanin in
      specialized organelles termed melanosomes, which regulates pigmentation of the
      skin, eyes, and hair. Gp96 is a constitutively expressed heat shock protein in
      the endoplasmic reticulum whose expression is further upregulated upon
      ultraviolet irradiation. However, the roles and mechanisms of this chaperone in
      pigmentation biology are unknown. In this study, we found that knockdown of gp96
      by RNA interference significantly perturbed melanin synthesis and blocked late
      melanosome maturation. Gp96 knockdown did not impair the expression of
      tyrosinase, an essential enzyme in melanin synthesis, but compromised its
      catalytic activity and melanosome translocation. Further, mice with melanocyte
      specific deletion of gp96 displayed decreased pigmentation. A mechanistic study
      revealed that the defect in melanogenesis can be rescued by activation of the
      canonical Wnt pathway, consistent with the critical roles of gp96 in chaperoning
      Wnt-coreceptor LRP6. Thus, this work uncovered the essential role of gp96 in
      regulating melanogenesis. 

PMID- 24024554
TI  - Plasminogen activator inhibitor-1 deficiency augments visceral mesothelial
      organization, intrapleural coagulation, and lung restriction in mice with carbon
      black/bleomycin-induced pleural injury.
AB  - Local derangements of fibrin turnover and plasminogen activator inhibitor (PAI)-1
      have been implicated in the pathogenesis of pleural injury. However, their role
      in the control of pleural organization has been unclear. We found that a C57Bl/6j
      mouse model of carbon black/bleomycin (CBB) injury demonstrates pleural
      organization resulting in pleural rind formation (14 d). In transgenic mice
      overexpressing human PAI-1, intrapleural fibrin deposition was increased, but
      visceral pleural thickness, lung volumes, and compliance were comparable to wild
      type. CBB injury in PAI-1(-/-) mice significantly increased visceral pleural
      thickness (P < 0.001), elastance (P < 0.05), and total lung resistance (P <
      0.05), while decreasing lung compliance (P < 0.01) and lung volumes (P < 0.05).
      Collagen, alpha-smooth muscle actin, and tissue factor were increased in the
      thickened visceral pleura of PAI-1(-/-) mice. Colocalization of alpha-smooth
      muscle actin and calretinin within pleural mesothelial cells was increased in CBB
      injured PAI-1(-/-) mice. Thrombin, factor Xa, plasmin, and urokinase induced
      mesothelial-mesenchymal transition, tissue factor expression, and activity in
      primary human pleural mesothelial cells. In PAI-1(-/-) mice, D-dimer and thrombin
      antithrombin complex concentrations were increased in pleural lavage fluids. The
      results demonstrate that PAI-1 regulates CBB-induced pleural injury severity via
      unrestricted fibrinolysis and cross-talk with coagulation proteases. Whereas
      overexpression of PAI-1 augments intrapleural fibrin deposition, PAI-1 deficiency
      promotes profibrogenic alterations of the mesothelium that exacerbate pleural
      organization and lung restriction. 

PMID- 24024555
TI  - Myopia and the long-term incidence of cataract and cataract surgery: the Blue
      Mountains Eye Study.
AB  - BACKGROUND: To assess the association between refractive errors and the 10-year
      incidence of cataract and cataract surgery. DESIGN: Population-based prospective
      study. PARTICIPANTS: Three thousand six hundred fifty-four persons aged 49+ years
      living in a well-defined geographical region were examined at baseline; 2564 were
      re-examined after 5 and/or 10 years. METHODS: Baseline refractive error was
      measured using autorefraction with subjective refinement. Lens photographs were
      taken at each visit and assessed using the Wisconsin Cataract Grading System.
      MAIN OUTCOME MEASURES: Long-term incidence of cataract and cataract surgery.
      RESULTS: Compared with emmetropia, high myopia was associated with increased
      incidence of nuclear cataract (adjusted odds ratio 3.01, 95% confidence intervals
      1.35-6.71). Low (odds ratio 1.86, confidence interval 1.03-3.35) and high myopia
      (odds ratio 7.80, confidence interval 3.51-17.35) were significantly associated
      with higher incidence of posterior subcapsular cataract. Low, moderate and high
      myopia were associated with increased incidence of cataract surgery (odds ratio
      2.54, confidence interval 1.76-3.68; odds ratio 2.61, confidence interval 1.45
      4.69; and odds ratio 4.81, confidence interval 2.33-9.93, respectively). Either
      any (odds ratio 1.35, confidence interval 1.08-1.69) or moderate hyperopia (odds
      ratio 1.76, confidence interval 1.32-2.34) was associated with increased
      incidence of nuclear cataract. CONCLUSION: Our longitudinal study confirms the
      association between myopia and an increased risk of nuclear and posterior
      subcapsular cataract. It also suggests that hyperopia may increase the risk of
      nuclear cataract.

PMID- 24024556
TI  - There are considerable drawbacks to oral anticoagulant for monitoring patients at
      home which should lead family physicians to discuss alternative or enhanced
      solutions: a cross-sectional study.
AB  - BACKGROUND: INR (International Normalized Ratio) is the biological reference test
      for the monitoring of vitamin K antagonist (VKA) therapy. Overdosage of VKAs
      causes about 17,000 hospitalizations and 5,000 deaths each year in France. To
      avoid these complications, monitoring and blood sampling conditions must be
      rigorous. In France, more than half of INRs are carried out at home. The aim was
      to determine blood-sampling conditions at home, transit time and the quality of
      the laboratory reagents used. METHOD: Questionnaire-based, descriptive
      epidemiological cross-sectional prevalence study involving home care nurses,
      family physicians (FPs) and clinical laboratories. SETTING: Brittany, France,
      2008. Study of the pre-analytical phase of INRs sampled at home and its influence
      on INR results. RESULTS: The study included 291 FPs, 249 home care nurses, and 49
      laboratories. 32.5% of reported INRs were outside the therapeutic range. Samples
      were drawn into unsuitable tubes in 5.5% of cases and delivered in a chilled
      condition in 9% of cases. In urban areas 50% of the tubes took more than 2 hours
      to reach the laboratory compared with 71% from rural areas. The average
      International Sensitivity Index (ISI) of the thromboplastin was 1.62. The INRs
      provided by the laboratories were not analyzable in 64.7% of cases where blood
      samples had been taken at home. CONCLUSION: Blood sample quality, transit time
      and the reagents used are currently inadequate. The majority of INRs taken at
      home are not reliable. FPs should consider these drawbacks in comparison with
      alternative solutions to increase patient safety.

PMID- 24024557
TI  - Annexin A10 is an immunohistochemical marker for adenocarcinoma of the upper
      gastrointestinal tract and pancreatobiliary system.
AB  - AIMS: Annexin A10 (ANXA10) is a calcium- and phospholipid-binding protein
      expressed normally in the gastric mucosa. In this study, we evaluated the
      potential use of ANXA10 as a diagnostic marker. METHODS AND RESULTS: We observed
      ANXA10 expression in the gastric mucosa, the Brunner gland of the duodenum and
      the urothelium, but absence of expression in other normal organs. Following the
      screening of 1327 primary carcinomas of major organs, we identified ANXA10
      expression in 46% of gastric, 72% of ampullary, 78% of pancreatic and 33% of
      biliary adenocarcinomas. ANXA10 was expressed in 83% of non-invasive urothelial
      carcinomas, but was expressed in only 9% of invasive urothelial carcinomas.
      ANAX10 was rarely expressed in carcinomas of other organs. Of 227 metastatic
      adenocarcinomas, ANXA10 was expressed in 83% of metastatic pancreatic and 47% of
      metastatic gastric adenocarcinomas, but was expressed in only 2% of metastatic
      adenocarcinomas from other organs. In the liver, the sensitivity and specificity
      for identifying the pancreas as the primary site of metastatic adenocarcinoma
      were 83 and 95%, respectively. CONCLUSION: Our study results indicate that the
      inclusion of ANXA10 in an immunohistochemical panel will be helpful in the
      differential diagnosis of adenocarcinoma of an unknown primary site.

PMID- 24024558
TI  - Correlated ions in a calcium channel model: a Poisson-Fermi theory.
AB  - We derive a continuum model, called the Poisson-Fermi equation, of biological
      calcium channels (of cardiac muscle, for example) designed to deal with crowded
      systems in which ionic species and side chains nearly fill space. The model is
      evaluated in three dimensions. It includes steric and correlation effects and is
      derived from classical hard-sphere lattice models of configurational entropy of
      finite size ions and solvent molecules. The maximum allowable close packing
      (saturation) condition is satisfied by all ionic species with different sizes and
      valences in a channel system, as shown theoretically and numerically. Unphysical
      overcrowding ("divergence") predicted by the Gouy-Chapman diffuse model (produced
      by a Boltzmann distribution of point charges with large potentials) does not
      occur with the Fermi-like distribution. Using probability theory, we also provide
      an analytical description of the implicit dielectric model of ionic solutions
      that gives rise to a global and a local formula for the chemical potential. In
      this primitive model, ions are treated as hard spheres and solvent molecules are
      described as a dielectric medium. The Poisson-Fermi equation is a local formula
      dealing with different correlations at different places. The correlation effects
      are apparent in our numerical results. Our results show variations of dielectric
      permittivity from bath to channel pore described by a new dielectric function
      derived as an output from the Poisson-Fermi analysis. The results are consistent
      with existing theoretical and experimental results. The binding curve of Poisson
      Fermi is shown to match Monte Carlo data and illustrates the anomalous mole
      fraction effect of calcium channels, an effective blockage of permeation of
      sodium ions by a tiny concentration (or number) of calcium ions. 

PMID- 24024560
TI  - LuF[SeO3]: the structural chameleon of lanthanoid fluoride oxoselenates(IV).
AB  - LuF[SeO3] is a compound that can easily be obtained by a solid-state reaction of
      Lu2O3, LuF3, and SeO2 with CsBr as the fluxing agent. The outstanding property of
      LuF[SeO3] is the appearance of two phase transitions within a range of less than
      200 K. With an increase in the coordination number for Lu(3+) from 7 to 8, the
      triclinic room-temperature modification changes at temperatures below -40 
      degrees C to the monoclinic low-temperature or high-pressure phase of LuF[SeO3].
      At the same time, room-temperature modification retains the structure but gains
      higher symmetry at the second phase transition of around +110  degrees C. This
      second transition can even be observed under a microscope using polarized light
      to see twinning lamellae disappear and reappear during this reversible process. 

PMID- 24024559
TI  - Late presentation to HIV/AIDS testing, treatment or continued care: clarifying
      the use of CD4 evaluation in the consensus definition.
AB  - OBJECTIVES: Late presentation to HIV/AIDS services compromises treatment outcomes
      and misses opportunities for biomedical and behavioural prevention. There has
      been significant heterogeneity in how the term 'late presentation' (LP) has been
      used in the literature. In 2011, a consensus definition was reached using CD4
      counts to define and measure late presenters and, while it is useful for clinical
      care, the consensus definition has several important limitations that we discuss
      in this article. METHODS: Using the spectrum of engagement in HIV care presented
      by Gardner and colleagues, this article highlights issues and opportunities
      associated with use of the consensus definition. RESULTS: The consensus
      definition is limited by three principal factors: (1) the CD4 count threshold of
      350 cells/MUL is being increasingly questioned as the biomedical justification
      grows for earlier initiation of treatment; (2) CD4 evaluations are conducted at
      multiple services providing HIV care; thus it remains unclear to which service
      the patient is presenting late; and (3) the limited availability of CD4
      evaluation restricts its use in determining the prevalence of LP in many
      settings. CONCLUSIONS: The consensus definition is useful because it describes
      the level of disease progression and allows for consistent evaluation of the
      prevalence and determinants of LP. Suggestions are provided for improving the
      application of the consensus definition in future research.

PMID- 24024561
TI  - Detection of antibodies specific to the non-structural proteins of fowl
      adenoviruses in infected chickens but not in vaccinated chickens.
AB  - Antibodies specific to the non-structural proteins of viruses are detected in
      virus-infected animals and show promise as a reliable diagnostic marker for virus
      infections. We examined the potential use of two non-structural proteins of fowl
      adenovirus (FAdV)-based, 100K and 33K, enzyme-linked immunosorbent assays
      (ELISAs) in the diagnosis of FAdVs. We cloned and expressed the 100K and 33K non
      structural protein genes of the FAdVs in the pGEX-4T-1 plasmid vector. Purified
      100K and 33K proteins alone or in combination were used as antigens in ELISAs.
      Antibodies specific to the 100K and 33K non-structural proteins were detected in
      chickens experimentally infected with FAdVs, but not in chickens vaccinated with
      inactivated FAdVs. In contrast, the agar gel precipitation (AGP) test detected
      FAdV-specific antibodies in 70.3% of the vaccinated chickens, suggesting that the
      non-structural protein-based ELISA could be used in the differential diagnosis of
      infected and vaccinated chickens. To further validate the 100K and 33K-based
      ELISA (100K-33K-ELISA) method, we compared its sensitivity and specificity with
      that of a whole virus-based ELISA and an AGP test in detecting FAdV-specific
      antibodies in 350 field samples. The results showed that the 100K-33K-ELISA
      exhibited a higher sensitivity than the AGP test and a comparable sensitivity and
      specificity to the whole virus ELISA. Overall, the 100K-33K-ELISA method is
      sensitive, specific and can be used to distinguish an acute FAdV infection from
      an inactivated virus-based vaccination response. 

PMID- 24024562
TI  - Uncoupling of allosteric and oligomeric regulation in a functional hybrid enzyme
      constructed from Escherichia coli and human ribonucleotide reductase.
AB  - An N-terminal-domain (NTD) and adjacent catalytic body (CB) make up subunit-alpha
      of ribonucleotide reductase (RNR), the rate-limiting enzyme for de novo dNTP
      biosynthesis. A strong linkage exists between ligand binding at the NTD and
      oligomerization-coupled RNR inhibition, inducible by both dATP and nucleotide
      chemotherapeutics. These observations have distinguished the NTD as an oligomeric
      regulation domain dictating the assembly of inactive RNR oligomers. Inactive
      states of RNR differ between eukaryotes and prokaryotes (alpha6 in human versus
      alpha4beta4 in Escherichia coli , wherein beta is RNR's other subunit); however,
      the NTD structurally interconnects individual alpha2 or alpha2 and beta2 dimeric
      motifs within the respective alpha6 or alpha4beta4 complexes. To elucidate the
      influence of NTD ligand binding on RNR allosteric and oligomeric regulation, we
      engineered a human- E. coli hybrid enzyme (HE) where human-NTD is fused to E.
      coli -CB. Both the NTD and the CB of the HE bind dATP. The HE specifically
      partners with E. coli -beta to form an active holocomplex. However, although the
      NTD is the sole physical tether to support alpha2 and/or beta2 associations in
      the dATP-bound alpha6 or alpha4beta4 fully inhibited RNR complexes, the binding
      of dATP to the HE NTD only partially suppresses HE activity and fully precludes
      formation of higher-order HE oligomers. We postulate that oligomeric regulation
      is the ultimate mechanism for potent RNR inhibition, requiring species-specific
      NTD-CB interactions. Such interdomain cooperativity in RNR oligomerization is
      unexpected from structural studies alone or biochemical studies of point mutants.

PMID- 24024563
TI  - Negative differential resistance by molecular resonant tunneling between neutral
      tribenzosubporphine anchored to a Au(111) surface and tribenzosubporphine cation
      adsorbed on to a tungsten tip.
AB  - Tribenzosubporphyrins are boron(III)-chelated triangular bowl-shaped ring
      contracted porphyrins that possess a 14pi-aromatic circuit. Their flat molecular
      shapes and discrete molecular orbital diagrams make them ideal for observation by
      scanning tunneling microscopy (STM). Expanding their applications toward single
      molecule-based devices requires a fundamental knowledge of single molecular
      conductance between tribenzosubporphines and the STM metal tip. We utilized a
      tungsten (W) STM tip to investigate the electronic properties of B-(5
      mercaptopentoxy)tribenzosubporphine 1 at the single molecular level. B-(5
      mercaptopentoxy)-tribenzosubporphine 1 was anchored to the Au(111) surface via
      reaction with 1-heptanethiol linkers that were preorganized as a self-assembled
      monolayer (C7S SAM) on the Au(111) substrate. This arrangement ensured that 1 was
      electronically decoupled from the metal surface. Differential conductance (dI/dV 
      V) measurements with the bare W tip exhibited a broad gap region of low
      conductance and three distinct responses at 2.4,-1.3, and -2.1 V. Bias-voltage
      dependent STM imaging of 1 at 65 K displayed a triangle shape at -2.1 < V < -1.3
      V and a circle shape at V < -2.1 V, reflecting its HOMO and HOMO-1, respectively.
      In addition, different conductance behaviors were reproducibly observed, which
      has been ascribed to the adsorption of a tribenzosubporphine-cation on the W tip.
      When using a W tip doped with preadsorbed tribenzosubporphine-cation, negative
      differential resistance (NDR) phenomena were clearly observed in a reproducible
      manner with a peak-to-valley ratio of 2.6, a value confirmed by spatial mapping
      conductance measurements. Collectively, the observed NDR phenomena have been
      attributed to effective molecular resonant tunneling between a neutral
      tribenzosubporphine anchored to the metal surface and a tribenzosubporphine
      cation adsorbed on a W tip. 

PMID- 24024564
TI  - Dietary trans fats enhance doxorubicin-induced cardiotoxicity in mice.
AB  - This study investigated the combined effects of trans fat diet (TFD) and
      doxorubicin upon cardiac oxidative, inflammatory, and coagulatory stress. TFD
      increased trans fatty acid deposit in heart (P < 0.05), and decreased protein C
      and antithrombin-III activities in circulation (P < 0.05). TFD plus doxorubicin
      treatment elevated activities of plasminogen activator inhibitor-1, lactate
      dehydrogenase, and creatine phosphokinase (P < 0.05). This combination also
      raised xanthine oxidase activity, and enhanced cardiac levels of reactive oxygen
      species, interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, and monocyte
      chemoattractant protein-1 than TFD or doxorubicin treatment alone (P < 0.05). TFD
      alone increased cardiac nuclear factor kappa B (NF-kappaB) activity (P < 0.05),
      but failed to affect expression of NF-kappaB and mitogen-activated protein kinase
      (MAPK) (P > 0.05). Doxorubicin treatment alone augmented cardiac activity, mRNA
      expression, and protein production of NF-kappaB and MAPK (P < 0.05). TFD plus
      doxorubicin treatment further upregulated cardiac expression of NF-kappaB p65, p
      p38, and p-ERK1/2 (P < 0.05). These findings suggest that TFD exacerbates
      doxorubicin-induced cardiotoxicity. 

PMID- 24024565
TI  - Heterosexual anal intercourse among men in Long Beach, California.
AB  - Anal intercourse poses a greater risk for human immunodeficiency virus (HIV)
      transmission than vaginal intercourse, and in recent years there has been a
      growing understanding that heterosexual anal intercourse (HAI) is not uncommon.
      However, the majority of the anal intercourse literature has focused on men who
      have sex with men. The little research on HAI has mostly looked at women, with
      limited work among men. This analysis examined the association between HAI and
      high-risk behaviors (N = 1,622) and sexual sensation seeking (N = 239) in a
      sample of men recruited from 2001 to 2012 in Long Beach, California. Almost half
      of the sample was non-Hispanic Black. The median age was 42 years, 42% were
      homeless, and 20% reported recent HAI. Men who reported HAI were likely to be
      Hispanic, were likely to be homeless, had a male partner, engaged in sex
      exchange, and used cocaine or amphetamines during sex. Men who reported HAI
      scored higher on the Sexual Sensation Seeking scale. This research supports other
      work showing the relationship between HAI and high-risk behaviors. More
      important, it contributes new knowledge by demonstrating the association between
      HAI and sexual sensation seeking. This research highlights the importance of
      personality traits when trying to understand sexual behavior and when developing
      HIV prevention interventions. 

PMID- 24024566
TI  - Repopulation of intrasynovial flexor tendon allograft with bone marrow stromal
      cells: an ex vivo model.
AB  - PURPOSE: Delayed healing is a common problem whenever tendon allografts are used
      for tendon or ligament reconstruction. Repopulating the allograft with host cells
      may accelerate tendon regeneration, but cell penetration into the allograft
      tendon is limited. Processing the tendon surface with slits that guide cells into
      the allograft substrate may improve healing. The purpose of this study was to
      describe a surface modification of allograft tendon that includes slits to aid
      cell repopulation and lubrication to enhance tendon gliding. METHODS: Canine
      flexor digitorum profundus tendons were used for this study. Cyclic gliding
      resistance was measured over 1000 cycles. Tensile stiffness was assessed for
      normal tendon, tendon decellularized with trypsin and Triton X-100
      (decellularized group), tendon decellularized and perforated with multiple slits
      (MS group) and tendon decellularized, perforated with slits and treated with a
      carbodiimide-derivatized hyaluronic acid and gelatin (cd-HA-gelatin) surface
      modification (MS-SM group). To assess tendon repopulation, bone marrow stromal
      cells (BMSCs) were used in the decellularized and MS groups. DNA concentration
      and histology were evaluated and compared to normal tendons and nonseeded
      decellularized tendons. RESULTS: The gliding resistance of the decellularized and
      MS groups was significantly higher compared with the normal group. There was no
      significant difference in gliding resistance between the decellularized and MS
      group. Gliding resistance of the normal group and MS-SM group was not
      significantly different. The Young's modulus was not significantly different
      among the four groups. The DNA concentration in the MS group was significantly
      lower than in normal tendons, but significantly higher than in decellularized
      tendons, with or without BMSCs. Viable BMSCs were found in the slits after 2
      weeks in tissue culture. CONCLUSIONS: Tendon slits can successfully harbor BMSCs
      without compromising their survival and without changing tendon stiffness.
      Surface modification restores normal gliding function to the slit tendon.
      CLINICAL RELEVANCE: A multislit tendon reseeded with BMSCs, with a surface
      treatment applied to restore gliding properties, may potentially promote tendon
      revitalization and accelerate healing for tendon or ligament reconstruction
      applications.

PMID- 24024567
TI  - Nurse burnout in China: a questionnaire survey on staffing, job satisfaction, and
      quality of care.
AB  - AIM: The investigators examined how nurse staffing affects nurse job satisfaction
      and quality of care. BACKGROUND: Inadequate nurse staffing is a worldwide issue
      with profound effects on nurse job satisfaction and quality of care. Few studies
      have examined the relationship between nurse staffing and job satisfaction and
      quality of care in China. METHOD: A cross-sectional design was adopted, wherein
      873 nurses were surveyed on demographics, nurse staffing, job-related burnout,
      job dissatisfaction, intent to leave, and quality of care. RESULT: The median
      patient-nurse ratio was five; 45.1% nurses reported high levels of job-related
      burnout, and 55.6%, job dissatisfaction. In adjusted regression models, patient
      nurse ratios of four or less were related to a decrease in the odds of job
      dissatisfaction (odds ratio 0.55, 95% confidence interval 0.36-0.85) and increase
      in the odds of quality of care (odds ratio 1.78, 95% confidence interval 1.02
      2.82). CONCLUSION: Nurse staffing is associated with job dissatisfaction and
      quality of care. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should
      maintain an adequate level of nurse staffing, referring to the patient-nurse
      ratio. They should create new initiatives to increase job satisfaction among
      nurses and to evaluate their effects.

PMID- 24024568
TI  - Development of chitosan/heparin nanoparticle-encapsulated cytolethal distending
      toxin for gastric cancer therapy.
AB  - AIM: The aim of this work was to develop pH-responsive nanoparticles
      encapsulating CdtB and to demonstrate that these particles represent a potential
      therapeutic agent for gastric cancer. MATERIALS & METHODS: Chitosan/heparin
      nanoparticle-encapsulated CdtB was prepared and the delivery efficiency was
      monitored by confocal laser scanning microscopy. The molecular basis of the
      nanoparticle-encapsulated CdtB-mediated p53 activation pathway was explored by
      immunoblot analysis. Antitumoral activities were investigated by analyzing the
      cell cycle and apoptosis. RESULTS: Chitosan/heparin nanoparticle-encapsulated
      CdtB preferentially inhibited the proliferation of cells derived from gastric
      cancer, but not in primary gastric epithelial cells. Treatment of cells with
      nanoparticle-encapsulated CdtB enhanced cell-cycle arrest at G2/M, followed by
      apoptosis. Moreover, our data showed that the mechanism for nanoparticle
      encapsulated CdtB-induced cell death was mediated by ATM-dependent DNA damage
      checkpoint responses. CONCLUSION: These findings indicate that chitosan/heparin
      nanoparticle-encapsulated CdtB could represent a new CdtB delivery strategy for
      the treatment of gastric cancer.

PMID- 24024569
TI  - Nanohybrids of silver particles on clay platelets delaminate Pseudomonas
      biofilms.
AB  - AIM: To evaluate the effectiveness of novel nanohybrids, composed of silver
      nanoparticles and nanoscale silicate platelets, to clear Pseudomonas aeruginosa
      biofilms. MATERIALS & METHODS: The nanohybrids were manufactured from an in situ
      reduction of silver salts in the silicate platelet dispersion, and then applied
      to biofilms in vitro and in vivo. RESULTS: In reference to the biocidal effects
      of gentamycin, the nanohybrids mitigated the spreading of the biofilms, and
      initiated robust cell death and exfoliation from the superficial layers of the
      biofilms in vitro. In vivo, the nanohybrids exhibited significant therapeutic
      effects by eliminating established biofilms from infected corneas and promoting
      the recovery of corneal integrity. CONCLUSION: All of the evaluations indicate
      the high potency of the newly developed silver nanoparticle/nanoscale silicate
      platelet nanohybrids for eliminating biofilms.

PMID- 24024570
TI  - Sustained broad-spectrum antibacterial effects of nanoliposomes loaded with
      silver nanoparticles.
AB  - BACKGROUND: The emergence of microbial resistance to antibiotics warrants the
      search for effective broad-spectrum antibacterial agents. Silver nanoparticles
      (AgNPs) have been used as antimicrobial agents. AgNPs encapsulated in
      nanolipososmes have been developed as effective antimicrobial agents. MATERIALS &
      METHODS: Nanoliposomes (<50 nm) were prepared using a modified reverse-phase
      evaporation method, and spherical, dextrose-capped AgNPs were synthesized. The
      prepared liposome AgNPs (LAgNPs) were characterized, and tested for their
      antibacterial effects. RESULTS: The size of LAgNPs is 25-80 nm. The release of
      AgNPs from nanoliposomes was sustained over 10 h. Complete growth inhibition of
      Eschericia coli, Salmonella enterica, Pseudomonas aeruginosa and Staphylococcus
      aureus was achieved using 180, 200, 160 and 120 uM, respectively, of LAgNPs.
      LAgNPs exhibited sustained broad-spectrum antibacterial effects compared with
      free AgNPs. CONCLUSION: Nanoliposomes loaded with AgNPs are potentially effective
      broad-spectrum antimicrobial agents. This new formula, which can be further
      fortified by encapsulation of additional established antibacterial agents, may be
      effective against antibiotic-resistant bacteria and also promote wound healing.

PMID- 24024571
TI  - Rapid dramatic alterations to the tumor microstructure in pancreatic cancer
      following irreversible electroporation ablation.
AB  - AIM: NanoKnife((r)) (Angiodynamics, Inc., NY, USA) or irreversible
      electroporation (IRE) is a newly available ablation technique to induce the
      formation of nanoscale pores within the cell membrane in targeted tissues. The
      purpose of this study was to elucidate morphological alterations following 30 min
      of IRE ablation in a mouse model of pancreatic cancer. MATERIALS & METHODS:
      Immunohistochemistry markers were compared with diffusion-weighted MRI apparent
      diffusion coefficient measurements before and after IRE ablation. RESULTS:
      Immunohistochemistry apoptosis index measurements were significantly higher in
      IRE-treated tumors than in controls. Rapid tissue alterations after 30 min of IRE
      ablation procedures (structural and morphological alterations along with
      significantly elevated apoptosis markers) were consistently observed and well
      correlated to apparent diffusion coefficient measurements. DISCUSSION: This
      imaging assay offers the potential to serve as an in vivo biomarker for
      noninvasive detection of tumor response following IRE ablation.

PMID- 24024572
TI  - Thoracic and abdominal lymphatic pump techniques inhibit the growth of S.
      pneumoniae bacteria in the lungs of rats.
AB  - BACKGROUND: Osteopathic physicians utilize manual medicine techniques called
      lymphatic pump techniques (LPT) to improve lymphatic flow and enhance immunity.
      Clinical studies report that LPT enhances antibody responses to bacterial
      vaccines, shortens duration of cough in patients with respiratory disease, and
      shortens the duration of intravenous antibiotic therapy and hospital stay in
      patients with pneumonia. The purpose of this study was to identify if thoracic
      LPT (Th-LPT) or abdominal LPT (Ab-LPT) would reduce Streptococcus pneumoniae
      colony-forming units (CFU) in the lungs of rats with acute pneumonia. METHODS AND
      RESULTS: Rats were nasally infected with S. pneumoniae and received either
      control, sham, Ab-LPT, or Th-LPT once daily for 3 consecutive days. On day 4 post
      infection, lungs were removed and bacteria were enumerated. Three daily
      applications of either Ab-LPT or Th-LPT were able to significantly (p<0.05)
      reduce the numbers of pulmonary bacteria compared to control and sham. There were
      no significant differences in the percentage or concentration of leukocytes in
      blood between groups, suggesting neither Ab-LPT nor Th-LPT release leukocytes
      into blood circulation. CONCLUSIONS: Our data demonstrate that LPT may protect
      against pneumonia by inhibiting bacterial growth in the lung; however, the
      mechanism of protection is unclear. Once these mechanisms are understood, LPT can
      be optimally applied to patients with pneumonia, which may substantially reduce
      morbidity, mortality, and frequency of hospitalization.

PMID- 24024574
TI  - Carrying yourself: self antigen composition of the lymphatic fluid.
AB  - Advances in proteomics methodology and instrumentation have allowed detailed
      characterization of the composition of lymph. Far from being a simple
      ultrafiltrate of blood plasma, lymph has been shown to carry a rich repertoire of
      proteins and peptides reflecting the tissue of origin and its physiological
      state. Peptides derived from lymph can be loaded on the MHCII proteins,
      particularly those present on immature and/or inactivated antigen presenting
      cells, and may play an important role in maintenance of peripheral tolerance.

PMID- 24024575
TI  - Lymphatic function and the immune response to microbial or viral infection.
AB  - The National Institute of Allergy and Infectious Diseases (NIAID) is the primary
      institute within the National Institutes of Health (NIH) that conducts and
      supports basic and applied research to better understand, treat, and ultimately
      prevent infectious, immunologic, and allergic diseases. For more than 60 years,
      NIAID research has led to new therapies, vaccines, diagnostic tests, and other
      technologies that have improved the health of millions of people in the United
      States and around the world. 

PMID- 24024573
TI  - Role of vascular and lymphatic endothelial cells in hantavirus pulmonary syndrome
      suggests targeted therapeutic approaches.
AB  - BACKGROUND: Hantaviruses in the Americas cause a highly lethal acute pulmonary
      edema termed hantavirus pulmonary syndrome (HPS). Hantaviruses nonlytically
      infect microvascular and lymphatic endothelial cells and cause dramatic changes
      in barrier functions without disrupting the endothelium. Hantaviruses cause
      changes in the function of infected endothelial cells that normally regulate
      fluid barrier functions. The endothelium of arteries, veins, and lymphatic
      vessels are unique and central to the function of vast pulmonary capillary beds
      that regulate pulmonary fluid accumulation. RESULTS: We have found that HPS
      causing hantaviruses alter vascular barrier functions of microvascular and
      lymphatic endothelial cells by altering receptor and signaling pathway responses
      that serve to permit fluid tissue influx and clear tissue edema. Infection of the
      endothelium provides several mechanisms for hantaviruses to cause acute pulmonary
      edema, as well as potential therapeutic targets for reducing the severity of HPS
      disease. CONCLUSIONS: Here we discuss interactions of HPS-causing hantaviruses
      with the endothelium, roles for unique lymphatic endothelial responses in HPS,
      and therapeutic targeting of the endothelium as a means of reducing the severity
      of HPS disease.

PMID- 24024576
TI  - The lymphatics and the inflammatory response: lessons learned from human
      lymphedema.
AB  - In lymphedema, there is a profound predisposition to infection with bacterial
      pathogens. It therefore seems appropriate to reconsider our unique functional
      definition of the lymphatic structures within a circulatory construct. While the
      lymphatics unquestionably fulfill a vital circulatory function, it seems more
      appropriate to view this complex network, comprised both of endothelial-lined
      vessels and of lymphoid tissue, as the nexus between the circulatory and immune
      systems. Viewed in this fashion, it becomes evident that the complex biology of
      regional lymphatic disruption is a manifestation of the interplay between these
      two vital bodily functions. Experimental lymph stasis in murine model has been
      utilized to effectively demonstrate the pathological attributes of human
      lymphedema, namely, inflammation, fat deposition, and fibrosis. Large-scale
      transcriptional corroborates the role of inflammatory mechanisms. The murine
      studies have set the stage for subsequent translational investigation of human
      lymphedema. Many of the gene expression pathways invoked by lymphedema are
      relevant to the inflammatory response and have provided a pragmatic approach to
      the successful identification of potentially relevant circulating biomarkers for
      human lymphedema.

PMID- 24024578
TI  - Lymphatics: where the circulation meets the immune system.

PMID- 24024579
TI  - Effects of sodium butyrate on growth performance, haematological and
      immunological characteristics of weanling piglets.
AB  - The experiment was conducted to study the effects of sodium butyrate (SB) on
      growth, haematological and immunological characteristics in weanling pigs. A
      total of 100 male piglets (Duroc*Landrace*Yorkshire) with a body weight of 8.0 +/
      0.2 kg weaned at the age of 28 days were randomly assigned to two treatments
      with five replicates and 10 pigs per replicate. Piglets received a basal diet
      (control group) or diets supplemented with 1000 mg/kg SB. The feeding trial
      lasted for 21 days. The results showed that dietary SB significantly decreased (p
      < 0.05) diarrhoea incidence of weaned piglets, but did not affect (p > 0.05) the
      average daily feed intake (ADFI), average daily gain (ADG) and feed to gain
      (F/G). Furthermore, piglets fed dietary SB had higher (p < 0.05) serum
      concentrations of glucose and triglycerides and lower (p < 0.05) serum
      concentrations of urea nitrogen, cortisol, D-lactic acid and diamine oxidase when
      compared with the control group. However, dietary SB did not affect
      concentrations of serum albumin, total protein, insulin and glucagon (p > 0.05).
      There were no significant (p > 0.05) treatment effects on serum IgA and IgM,
      whereas serum IgG concentration and IgA+ cell count in jejunum from pigs fed SB
      were significantly higher (p < 0.05) than in those given the basal diet. In
      conclusion, the present study indicated that dietary SB significantly decreased
      diarrhoea incidence of weaned piglets and increased the efficiency of nitrogen
      utilization. Also, dietary SB could regulate and enhance the immune function of
      piglets by increasing the serum IgG concentration and IgA+ cell count in jejunum.
      Our results suggest that SB may reduce some of the adverse effects of weaning
      stress and play an important role in maintaining the integrity of intestinal
      mucosa. 

PMID- 24024577
TI  - Lymphatic function and immune regulation in health and disease.

PMID- 24024581
TI  - Antimony-mediated control of misfit dislocations and strain at the highly lattice
      mismatched GaSb/GaAs interface.
AB  - Determining the atomic structure of misfit dislocations at highly lattice
      mismatched interface is essential to optimize the quality of the epitaxial layer.
      Here, with aberration corrected scanning transmission electron microscopy at sub
      Angstrom resolution and molecular dynamics simulation, we investigated the atomic
      structure of misfit dislocations at GaSb/GaAs interface. New types of Lomer
      misfit dislocation formed on an Sb wetting monolayer were observed, in contrast
      to a conventional misfit dislocation whose core is located at interface. These Sb
      mediated dislocations have highly localized cores and offer more capability to
      confine the mismatch strain at the interface. The low strain atomic configuration
      of Sb-mediated dislocations is driven by minimization of the core energy. This
      unveiled mechanism may pave the way to the growth of high quality hetero
      epitaxial layers. 

PMID- 24024580
TI  - FGT-1 is the major glucose transporter in C. elegans and is central to aging
      pathways.
AB  - Caenorhabditis elegans is widely used as a model for investigation of the
      relationships between aging, nutrient restriction and signalling via the DAF-2
      (abnormal dauer formation 2) receptor for insulin-like peptides and AGE-1 [ageing
      alteration 1; orthologue of PI3K (phosphoinositide 3-kinase)], but the identity
      of the glucose transporters that may link these processes is unknown. We
      unexpectedly find that of the eight putative GLUT (glucose transporter)-like
      genes only the two splice variants of one gene have a glucose transport function
      in an oocyte expression system. We have named this gene fgt-1 (facilitated
      glucose transporter, isoform 1). We show that knockdown of fgt-1 RNA leads to
      loss of glucose transport and reduced glucose metabolism in wild-type worms. The
      FGT-1 glucose transporters of C. elegans thus play a key role in glucose energy
      supply to C. elegans. Importantly, knockdown of fgt-1 leads to an extension of
      lifespan equivalent, but not additive, to that observed in daf-2 and age-1 mutant
      worms. The results of the present study are consistent with DAF-2 and AGE-1
      signalling stimulating glucose transport in C. elegans and this process being
      associated with the longevity phenotype in daf-2 and age-1 mutant worms. We
      propose that fgt-1 constitutes a common axis for the lifespan extending effects
      of nutrient restriction and reduced insulin-like peptide signalling.

PMID- 24024582
TI  - Single-walled carbon nanotubes mediated targeted tamoxifen delivery system using
      aspargine-glycine-arginine peptide.
AB  - An aspargine-glycine-arginine (NGR) peptide modified single-walled carbon
      nanotubes (SWCNTs) system, developed by a simple non-covalent approach, could be
      loaded with the anticancer drug tamoxifen (TAM). This TAM-loaded NGR modified
      SWCNTs (TAM/NGR-SWCNTs) not only retained both optical properties of SWCNTs and
      cytotoxicity of TAM, but also could accumulate in tumors and enter into 4T1
      cells, which facilitated combination chemotherapy with photothermal therapy in
      one targeting system. Enhanced cellular uptake, antitumor effect and cell
      apoptosis of TAM/NGR-SWCNTs on 4T1 cells were observed in vitro, compared with
      the TAM solution, TAM/SWCNTs and photothermal therapy alone. In vivo
      investigation of TAM/NGR-SWCNTs in tumor-bearing mice further confirmed that this
      system possessed much higher tumor targeting capacity and antitumor efficacy than
      the control, especially with the near-infrared-laser irradiation treatment.
      Moreover, it demonstrated negligible systematic toxicity through the
      histopathological analysis. All these results suggest TAM/NGR-SWCNTs are
      promising for high targeted efficiency and treatment efficacy and low side
      effects of future cancer therapy by synergistic effect of chemo-photothermal
      combination.

PMID- 24024583
TI  - Epoxide pathways improve model predictions of isoprene markers and reveal key
      role of acidity in aerosol formation.
AB  - Isoprene significantly contributes to organic aerosol in the southeastern United
      States where biogenic hydrocarbons mix with anthropogenic emissions. In this
      work, the Community Multiscale Air Quality model is updated to predict isoprene
      aerosol from epoxides produced under both high- and low-NOx conditions. The new
      aqueous aerosol pathways allow for explicit predictions of two key isoprene
      derived species, 2-methyltetrols and 2-methylglyceric acid, that are more
      consistent with observations than estimates based on semivolatile partitioning.
      The new mechanism represents a significant source of organic carbon in the lower
      2 km of the atmosphere and captures the abundance of 2-methyltetrols relative to
      organosulfates during the simulation period. For the parametrization considered
      here, a 25% reduction in SOx emissions effectively reduces isoprene aerosol,
      while a similar reduction in NOx leads to small increases in isoprene aerosol. 

PMID- 24024584
TI  - Ultrasensitive determination of copper in complex biological media based on
      modulation of plasmonic properties of gold nanorods.
AB  - Accurate determination of copper in complex biological media such as cells is
      quite difficult, and an analytical strategy based on copper-modulated formation
      of core-shell gold nanorods is described. Selective and label-free sensing can be
      achieved by measuring the change in the localized surface plasmon resonance
      absorption. The technique can determine trace amounts of copper in human serum,
      urine, and red blood cells without or with minimal sample pretreatment. The Cu
      detection limits are 20.67 MUM in human serum, 0.193 MUM in human urine, and 3.09
      * 10(-16) g in a single cell. The advantages of the technique are the high
      selectivity, simple or no sample pretreatment, and label free. Boasting a
      practical detection limit down to 2 fM, only 10(3) red blood cells are needed to
      conduct the analysis and the technique may be extended to the detection of trace
      amounts of copper in a single cell. 

PMID- 24024585
TI  - Treatment of seronegative spondyloarthropathy-associated uveitis with golimumab:
      retrospective case series.

PMID- 24024586
TI  - Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid
      receptor function in airway smooth muscle cells.
AB  - Like many steroid receptors, the glucocorticoid (GC) receptor (GR) is a
      phosphoprotein. Although there are multiple phosphorylation sites critical for GR
      transcriptional activity (i.e., serine [S]203, S211, and S226), their respective
      role in driving GR functions is highly cell specific. We have recently identified
      protein phosphatase 5 as an essential Ser/Thr phosphatase responsible for
      impairing GR function via S211 dephosphorylation in airway smooth muscle (ASM)
      cells. Because p38 mitogen-activated protein kinase (MAPK) directly
      phosphorylates GR in different cell types in a stimulus- and cell-dependent
      manner, we investigated the role of p38 MAPK on GR phosphorylation and function
      in ASM cells. Cells were transfected with 100 nM p38 MAPK small interfering RNA
      or 2 MUg MAPK kinase 3 expression vector (a specific kinase that directly
      activates p38 MAPK) in the presence or absence of fluticasone (100 nM) and/or p38
      MAPK pharmacological inhibitor SB203580. We found that p38 MAPK blockade
      positively regulates GR nuclear translocation and GR-dependent induction of the
      steroid-target gene GC-induced leucine zipper in a hormone-independent manner. We
      also found that p38 MAPK-dependent regulation of GR functions was associated with
      a differential action on GR phosphorylation at S203 and S211 residues. This study
      demonstrated that the inactive state of GR in resting conditions is not only
      ensured by the absence of the GC ligand but also by p38 MAPK-dependent
      phosphorylation of unliganded GR at specific residues, which appears to be
      important in determining the overall GC responsiveness of ASM cells. 

PMID- 24024588
TI  - The expression of LIM-homeobox genes, Lhx1 and Lhx5, in the forebrain is
      essential for neural retina differentiation.
AB  - Elucidating the mechanisms underlying eye development is essential for advancing
      the medical treatment of eye-related disorders. The primordium of the eye is an
      optic vesicle (OV), which has a dual potential for generation of the developing
      neural retina and retinal pigment epithelium. However, the factors that regulate
      the differentiation of the retinal primordium remain unclear. We have previously
      shown that overexpression of Lhx1 and Lhx5, members of the LIM-homeobox genes,
      induced the formation of a second neural retina from the presumptive pigmented
      retina of the OV. However, the precise timing of Lhx1 expression required for
      neural retina differentiation has not been clarified. Moreover, RNA interference
      of Lhx5 has not been previously reported. Here, using a modified electroporation
      method, we show that, Lhx1 expression in the forebrain around stage 8 is required
      for neural retina formation. In addition, we have succeeded in the knockdown of
      Lhx5 expression, resulting in conversion of the neural retina region to a pigment
      vesicle-like tissue, which indicates that Lhx5 is also required for neural retina
      differentiation, which correlates temporally with the activity of Lhx1. These
      results suggest that Lhx1 and Lhx5 in the forebrain regulate neural retina
      differentiation by suppressing the development of the retinal pigment epithelium,
      before the formation of the OV. 

PMID- 24024587
TI  - Shared decision-making in antihypertensive therapy: a cluster randomised
      controlled trial.
AB  - BACKGROUND: Hypertension is one of the key factors causing cardiovascular
      diseases. A substantial proportion of treated hypertensive patients do not reach
      recommended target blood pressure values. Shared decision making (SDM) is to
      enhance the active role of patients. As until now there exists little information
      on the effects of SDM training in antihypertensive therapy, we tested the effect
      of an SDM training programme for general practitioners (GPs). Our hypotheses are
      that this SDM training (1) enhances the participation of patients and (2) leads
      to an enhanced decrease in blood pressure (BP) values, compared to patients
      receiving usual care without prior SDM training for GPs. METHODS: The study was
      conducted as a cluster randomised controlled trial (cRCT) with GP practices in
      Southwest Germany. Each GP practice included patients with treated but
      uncontrolled hypertension and/or with relevant comorbidity. After baseline
      assessment (T0) GP practices were randomly allocated into an intervention and a
      control arm. GPs of the intervention group took part in the SDM training. GPs of
      the control group treated their patients as usual. The intervention was blinded
      to the patients. Primary endpoints on patient level were (1) change of patients'
      perceived participation (SDM-Q-9) and (2) change of systolic BP (24h-mean).
      Secondary endpoints were changes of (1) diastolic BP (24h-mean), (2) patients'
      knowledge about hypertension, (3) adherence (MARS-D), and (4) cardiovascular risk
      score (CVR). RESULTS: In total 1357 patients from 36 general practices were
      screened for blood pressure control by ambulatory blood pressure monitoring
      (ABPM). Thereof 1120 patients remained in the study because of uncontrolled (but
      treated) hypertension and/or a relevant comorbidity. At T0 the intervention group
      involved 17 GP practices with 552 patients and the control group 19 GP practices
      with 568 patients. The effectiveness analysis could not demonstrate a significant
      or relevant effect of the SDM training on any of the endpoints. CONCLUSION: The
      study hypothesis that the SDM training enhanced patients' perceived participation
      and lowered their BP could not be confirmed. Further research is needed to
      examine the impact of patient participation on the treatment of hypertension in
      primary care. TRIAL REGISTRATION: German Clinical Trials Register (DRKS):
      DRKS00000125.

PMID- 24024589
TI  - Fungal and bacterial utilization of organic substrates depends on substrate
      complexity and N availability.
AB  - There is growing evidence of a direct relationship between microbial community
      composition and function, which implies that distinct microbial communities vary
      in their functional properties. The aim of this study was to determine whether
      differences in initial substrate utilization between distinct microbial
      communities are due to the activities of certain microbial groups. We performed a
      short-term experiment with beech forest soils characterized by three different
      microbial communities (winter and summer community, and a community from a tree
      girdling plot). We incubated these soils with different (13) C-labelled
      substrates with or without inorganic N addition and analyzed microbial substrate
      utilization by (13) C-phospholipid fatty acid (PLFA) analysis. Our results
      revealed that the fate of labile C (glucose) was similar in the three microbial
      communities, despite differences in absolute substrate incorporation between the
      summer and winter community. The active microbial community involved in
      degradation of complex C substrates (cellulose, plant cell walls), however,
      differed between girdling and control plots and was strongly affected by
      inorganic N addition. Enhanced N availability strongly increased fungal
      degradation of cellulose and plant cell walls. Our results indicate that fungi,
      at least in the presence of a high N supply, are the main decomposers of
      polymeric C substrates.

PMID- 24024590
TI  - Pulmonary metastatic nodules of uterine low-grade endometrial stromal sarcoma:
      histopathological and immunohistochemical analysis of 10 cases.
AB  - AIMS: To identify histopathological and immunohistochemical findings that aid
      diagnosis of metastatic endometrial stromal sarcoma (ESS) in small biopsy
      specimens of the lung. METHODS AND RESULTS: We reviewed the histology of 46 lung
      nodules from 10 cases of pulmonary metastatic ESS. Biopsy sections were analysed
      by immunohistochemistry to highlight blood and lymphatic vasculature, and for
      expression of CD10 and oestrogen receptor (ER). Various histological changes were
      identified that could mislead in making a diagnosis on small biopsy samples:
      haemangiopericytomatous blood vessels (39%), absence of characteristic spiral
      arteriole-like vasculature (26%), intratumoral cysts formed by dilatation of
      airways (22%) or intratumoral myxoid change (11%), prominent interstitial
      collagen deposits (48%), foam cell infiltration (4%) and smooth muscle
      differentiation (2%). Peribronchial/peribronchiolar distribution of tumour cells
      with juxtaepithelial growth was a frequent feature, observed in 59% of nodules.
      In two very small nodules the lesion was barely recognizable histologically;
      tumour cells were detected only by expression of ER and CD10. CONCLUSIONS:
      Combined staining for ER and CD10 can be helpful in avoiding an erroneous
      diagnosis. As lymphatics are not normally present in the juxtaepithelial
      bronchial/bronchiolar wall, juxtaepithelial tumour growth beneath the bronchial
      epithelium in early metastatic lesions indicates a haematogenous metastastic
      route through the bronchial artery.

PMID- 24024591
TI  - Why do arginine and lysine organize lipids differently? Insights from coarse
      grained and atomistic simulations.
AB  - An important puzzle in membrane biophysics is the difference in the behaviors of
      lysine (Lys) and arginine (Arg) based peptides at the membrane. For example, the
      translocation of poly-Arg is orders of magnitude faster than that of poly-Lys.
      Recent experimental work suggests that much of the difference can be inferred
      from the phase behavior of peptide/lipid mixtures. At similar concentrations,
      mixtures of phosphatidylethanolamine (PE) and phosphatidylserine (PS) lipids
      display different phases in the presence of these polypeptides, with a
      bicontinuous phase observed with poly-Arg peptides and an inverted hexagonal
      phase observed with poly-Lys peptides. Here we show that simulations with the
      coarse-grained (CG) BMW-MARTINI model reproduce the experimental results. An
      analysis using atomistic and CG models reveals that electrostatic and glycerol
      peptide interactions play a crucial role in determining the phase behavior of
      peptide-lipid mixtures, with the difference between Arg and Lys arising from the
      stronger interactions of the former with lipid glycerols. In other words, the
      multivalent nature of the guanidinium group allows Arg to simultaneously interact
      with both phosphate and glycerol groups, while Lys engages solely with phosphate;
      this feature of amino acid/lipid interactions has not been emphasized in previous
      studies. The Arg peptides colocalize with PS in regions of high negative Gaussian
      curvature and stabilize the bicontinuous phase. Decreasing the strength of either
      the electrostatic interactions or the peptide-glycerol interactions causes the
      inverted hexagonal phase to become more stable. The results highlight the utility
      of CG models for the investigation of phase behavior but also emphasize the
      subtlety of the phenomena, with small changes in specific interactions leading to
      qualitatively different phases. 

PMID- 24024592
TI  - Circadian preference and thinking styles: implications for school achievement.
AB  - Research has shown that thinking styles could have an influence on academic
      achievement. Previous studies have described that evening types are usually right
      thinkers who tend to be creative and intuitive, whereas morning types tend to be
      left-thinkers who prefer verbal and analytic strategies in processing
      information. However, these studies have been realized among undergraduates, who
      have more freedom to choose their time schedules according to their circadian
      preference than adolescents or adult workers. On other hand, the relationship
      between thinking styles and circadian preference has not been analyzed
      considering school achievement. The present study aims (1) to investigate the
      relationship between circadian preference, that is, behavioral differences in
      circadian rhythmic expression, and thinking styles, referring to the preference
      toward information processing typical of the right versus the left cerebral
      hemisphere; and (2) to test the implications for self-reported school
      achievement. A sample of 1134 preadolescents and adolescents (581 girls; mean +/-
      SD age: 12.1 +/- 1.47, range: 10-14 yrs) completed the Morningness-Eveningness
      Scale for Children (MESC) as measure of circadian preference (morning, neither,
      or evening types), the Hemispheric Preference Test (HPT), conceived as a tool to
      measure thinking styles (right-, balanced-, and left-thinkers), and self-reported
      school achievement. Results indicated a greater percentage of left-thinkers among
      morning types and a greater percentage of right-thinkers among evening types. No
      differences were found among balanced-thinkers and neither types. Morning types
      and left-thinkers reported the highest subjective level of achievement, followed
      by evening types and left-thinkers, and morning types and right-thinkers. Evening
      types and right-thinkers reported the lowest subjective level of achievement.
      Finally, multivariate regression analysis indicated that age, left hemisphere and
      morning preferences accounted for 14.2% of total variance on self-reported
      achievement.

PMID- 24024593
TI  - Contribution of intramolecular NH...O hydrogen bonds to magnesium-carboxylate
      bonds.
AB  - A series of magnesium carboxylate complexes containing intramolecular NH...O
      hydrogen bonds were synthesized. Their molecular structures were determined by X
      ray analysis. A direct NH...O hydrogen bond to the coordinated oxygen atom
      elongated the Mg-O bond, while a hydrogen bond to the carbonyl group shortened
      the Mg-O bond. Double NH...O hydrogen bonds significantly lowered the basicity of
      the carboxylate anion and prevented coordination to the Mg ion in a trans
      configuration; however, a cis-dicarboxylate complex was successfully obtained.
      Strong coordination of water to the Mg(2+) ion stabilizes the weak Mg-carboxylate
      bond at the trans position. In contrast, a weak Mg-carboxylate bond strengthens
      the Mg-O(water) bond, probably increasing the acidity. Based on the experimental
      results and theoretical calculations, a new switching mechanism is proposed. In
      the proposed mechanism, the acidity of the coordinated water on magnesium is
      controlled during catalytic hydrolysis in endonuclease. 

PMID- 24024594
TI  - Staphylococcus aureus nasal carriage among patients and health care workers in
      Sao Tome and Principe.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen
      worldwide. However, data on MRSA prevalence in the African continent are scarce
      and nonexistent for Sao Tome and Principe. In November 2010 and April 2012, a
      total of 332 individuals (258 patients and 74 health care workers [HCW]) from
      Hospital Dr. Ayres Menezes in Sao Tome and Principe, were screened for S. aureus
      and MRSA carriage. Fifty-two persons (15.7%) were S. aureus nasal carriers out of
      which 14 (26.9%) were colonized with MRSA. MRSA isolates belonged to three clonal
      complexes: CC8 (PFGE type B-ST8-t064/t451-IVg/V), CC88 (PFGE E-ST88-t186/t786
      IVa), and CC5 (PFGE K-ST5-t105-IVa/PFGE K-ST105-t002-II). A higher genetic
      diversity was found among methicillin-susceptible S. aureus (MSSA) isolates where
      58.5% (n=24) belonged to four major lineages: PFGE type A-ST15-t084; PFGE C-ST508
      t861 or related; PFGE D-ST152-t355 or related; and PFGE G-ST121-t159/t2304.
      Despite the common nonmultiresistant profile, 98% of the isolates harbored two or
      more virulence factors. Panton-Valentine leukocidine was detected in 36% of the
      isolates, all MSSA. S. aureus cross-transmission between HCW and patients in the
      pediatric and medicine wards and the detection of identical MRSA strains among
      patients in two different wards evidenced the need of implementation of
      additional infection control measures in this hospital. 

PMID- 24024595
TI  - Use of bacterial magnetosomes in the magnetic hyperthermia treatment of tumours:
      a review.
AB  - We review the most recent and significant results published in the field of
      magnetotactic bacteria (MTB), in particular data relating to the use of bacterial
      magnetosomes in magnetic hyperthermia for the treatment of tumours. We review
      different methods for cultivating MTB and preparing suspensions of bacterial
      magnetosomes. As well as the production of magnetosomes, we also review key data
      on the toxicity of the magnetosomes as well as their heating and anti-tumour
      efficiencies. The toxicity and efficiency of magnetosomes needs to be understood
      and the risk-benefit ratio with which to evaluate their use in the magnetic
      hyperthermia treatment of tumours needs to be measured.

PMID- 24024596
TI  - User image mismatch in anaesthesia alarms: a cognitive systems analysis.
AB  - In this study, principles of Cognitive Systems Engineering are used to better
      understand the human-machine interaction manifesting in the use of anaesthesia
      alarms. The hypothesis is that the design of the machine incorporates built-in
      assumptions of the user that are discrepant with the anaesthesiologist's self
      assessment, creating 'user image mismatch'. Mismatch was interpreted by focusing
      on the 'user image' as described from the perspectives of both machine and user.
      The machine-embedded image was interpreted through document analysis. The user
      described image was interpreted through user (anaesthesiologist) interviews.
      Finally, an analysis was conducted in which the machine-embedded and user
      described images were contrasted to identify user image mismatch. It is concluded
      that analysing user image mismatch expands the focus of attention towards macro
      elements in the interaction between man and machine. User image mismatch is
      interpreted to arise from complexity of algorithm design and incongruity between
      alarm design and tenets of anaesthesia practice. PRACTITIONER SUMMARY: Cognitive
      system engineering principles are applied to enhance the understanding of the
      interaction between anaesthesiologist and alarm. The 'user image' is interpreted
      and contrasted from the perspectives of machine as well as the user. Apparent
      machine-user mismatch is explored pertaining to specific design features.

PMID- 24024598
TI  - Multifunctional nanoparticles for targeting cancer and inflammatory diseases.
AB  - The interplay between cancer and inflammation has been well documented over the
      years and the role of nanomedical technologies for treating both these diseases
      has become evident over the past few decades. With the advances in nanoparticle
      based imaging and therapeutic platforms that can exploit the pathological
      conditions of the tumor and the inflamed sites to effectively deliver drugs,
      genes and imaging/contrast agents; the management of such conditions with
      favorable therapeutic outcomes seems plausible. This review will summarize some
      of the latest advances in the field of targeted nanomedicine development to
      combat cancer and inflammation. Illustrative examples of multifunctional-targeted
      nanosystems are presented that highlight their potential in delivering diverse
      payloads, including small molecule drugs, nucleic acids and imaging agents for
      simultaneous theranostic interventions.

PMID- 24024599
TI  - "Is bipolar disorder an endocrine condition?" Glucose abnormalities in bipolar
      disorder.

PMID- 24024600
TI  - A review of needle-free sumatriptan injection for rapid control of migraine.
AB  - The treatment of migraine was transformed in 1992 with the introduction of the
      first triptan-based therapy, subcutaneous (SC) sumatriptan. SC sumatriptan has
      high efficacy and a rapid onset of action compared with other available triptans
      and formulations presumably because of its short Tmax, high Cmax, and avoidance
      of enteral absorption. Because of these characteristics, SC sumatriptan is still
      considered the most reliably and rapidly effective self-administered medication
      available for acute migraine. Even so, it is relatively little used possibly in
      part because of patient "needle-phobia." The needle-free sumatriptan injection
      system (Sumavel DosePro) was developed to address this concern. Clinical trials
      have shown that the needle-free system is bioequivalent to needle-based injection
      systems, easy to use, and capable of providing rapid and effective symptom relief
      for many migraine episodes. Sumavel DosePro is an effective treatment for
      migraine and should be part of the therapeutic armamentarium, particularly in
      cases where a rapid onset of action is critical or where oral administration is
      problematic.

PMID- 24024601
TI  - Sumatriptan iontophoretic transdermal system: history, study results, and use in
      clinical practice.
AB  - Nausea is a common symptom of migraine, and current treatment guidelines
      recommend non-oral formulations for nauseated or vomiting patients. Transdermal
      delivery of sumatriptan, a 5-hydroxytryptamine1B1D agonist with established
      efficacy in patients with migraine, represents a novel approach to acute
      treatment. The sumatriptan iontophoretic transdermal system circumvents the
      gastrointestinal tract by using low-level electrical energy to transport
      sumatriptan across the skin. In multiple well-controlled studies, the sumatriptan
      transdermal system has shown that it provides consistent drug delivery with low
      interpatient variability, rapid relief of migraine pain and associated symptoms,
      and an excellent overall safety profile, with a low incidence of triptan
      sensation adverse events. Patients and health care professionals who have used
      the sumatriptan transdermal system give it high ratings for ease of
      use/application. The sumatriptan transdermal system will allow a wide range of
      patients, especially those who experience migraine-related nausea or vomiting, to
      receive the benefits of migraine-specific therapy. 

PMID- 24024602
TI  - Orally inhaled dihydroergotamine: a review.
AB  - Orally inhalable dihydroergotamine (iDHE), before the US Food and Drug
      Administration in 2013 for consideration for approval for acute treatment of
      episodic migraine in adults, is a user-friendly formulation of an older
      medication. Dihydroergotamine (DHE) has a heterogeneous receptor profile, central
      penetration, and persistent receptor binding that may account for its clinical
      prolonged benefits in acute treatment of migraine. The same features may result
      in the ability of DHE to reverse central sensitization and allodynia and to
      maintain efficacy deep into attacks. These characteristics make DHE particularly
      useful in treating migraine upon awakening, prolonged migraine and status
      migrainosus, menstrually related migraine, and for bridging patients out of
      medication-overuse headache/chronic migraine. The inhalable formulation has
      helpful pharmacokinetics, with a lower maximal serum concentration than
      intravenous DHE which may account for minimal nausea, and less binding to the
      potentially toxic serotonin2B receptor. The inhaler itself is designed for
      delivery of reproducible aliquots of intrapulmonary DHE with only nominal need
      for patient coordination. The inhalable form allows for bypassing the
      gastrointestinal tract in the setting of migraine nausea or vomiting, and greatly
      reduces first-pass effect. No drug-related serious adverse events were reported
      during the Phase 3 study of iDHE. Product taste and nausea were the most common
      side effects in both the Phase 3 regulatory trial and in the safety extension
      trial. Limitations for use of iDHE are those for any ergot or triptan, ie,
      contraindication in the setting of vascular disease. In addition, iDHE is
      metabolized by the cytochrome P450 3A4 liver enzymatic system. Inhalable DHE
      provides the promise of a new formulation of a valued medication with important
      clinical features, useful deep into attacks in a variety of situations. 

PMID- 24024603
TI  - OnabotulinumtoxinA for the treatment of headache.
AB  - Botulinum toxin, a potent muscle relaxant, has been found to have analgesic
      effects in patients with various pain syndromes. Both in vitro and in vivo
      studies showed the ability of the toxin to block the release of pain
      neurotransmitters, such as substance P, glutamate, and calcitonin gene-related
      peptide. The effect of the toxin, and specifically of one of its serotypes,
      botulinum neurotoxin type A, on headaches, has been extensively studied. This
      serotype is available in the United States in 3 forms, including as
      onabotulinumtoxinA. Data from clinical trials confirmed the efficacy, safety, and
      tolerability of onabotulinumtoxinA in the prophylactic treatment of chronic
      migraine, the most severe and debilitating type of migraine, in adults. The drug
      was approved by the Food and Drug Administration for this indication in 2010. The
      drug was not found to be effective for episodic migraine or tension-type
      headache. Noncontrolled studies suggest the efficacy of the toxin for headache
      associated with craniocervical dystonia. Proper injection technique and
      appropriate patient selection are essential for achieving positive results after
      treatment with onabotulinumtoxinA. The recommended injection paradigm combines a
      fixed site/fixed dose and follow the pain approaches, with the toxin injected to
      multiple sites of the head and neck, at a total dose of 155U-195U. The treatment
      is given at intervals of 12 weeks on average. The efficacy of onabotulinumtoxinA
      for some headaches, its long duration of action, and its favorable adverse effect
      profile make it a viable treatment option for the appropriate headache patients.
      The drug may be particularly suitable for patients who cannot tolerate, or are
      not compliant with, the daily intake of oral headache preventive drugs. 

PMID- 24024604
TI  - Intranasal zolmitriptan for the treatment of acute migraine.
AB  - OBJECTIVE: To review the pharmacokinetics, efficacy, tolerability, and patient
      acceptance of zolmitriptan nasal spray (NS). BACKGROUND: Gastroparesis may delay
      or diminish the absorption of oral triptans, and nausea or vomiting may do the
      same and/or make it difficult to take a tablet. Some migraineurs require or
      prefer faster relief than oral medications provide. Injectable triptans provide
      the fastest drug delivery into the bloodstream, but many patients are reluctant
      to use them. Nasal sprays may address some of the problems with tablets and
      injectables while still providing rapid absorption of drug. METHODS: Non
      systematic review. RESULTS: Significant levels of zolmitriptan NS are detectable
      in plasma within 2-5 minutes, and the rapid absorption is due to early uptake
      through the nasal mucosa. In 2 randomized trials, users of zolmitriptan NS were
      significantly more likely than placebo recipients to be pain-free at 15 minutes
      post-dose, the first time point measured, and about half of patients had
      sustained response at 24 hours. Studies in which patients could treat a migraine
      of any severity have documented significant headache response or relief with
      zolmitriptan NS at 10 minutes. In one trial, the rate of total symptom relief was
      significantly better with the NS than with placebo from 30 minutes post-dose. The
      most common side effect of zolmitriptan NS is unusual taste. Patient satisfaction
      studies indicate that zolmitriptan NS is appreciated for its speed of onset, ease
      of use, reliability, and overall efficacy. CONCLUSIONS: Zolmitriptan NS provides
      onset of headache relief within 10 minutes for some patients and quickly
      abolishes some of the major migraine symptoms. Good candidates are migraineurs
      whose episodes rapidly escalate to moderate-to-severe pain and those who have
      morning migraine, have a quick time to vomiting, or have failed oral triptans.

PMID- 24024605
TI  - Breath powered nasal delivery: a new route to rapid headache relief.
AB  - The nose offers an attractive noninvasive alternative for drug delivery. Nasal
      anatomy, with a large mucosal surface area and high vascularity, allows for rapid
      systemic absorption and other potential benefits. However, the complex nasal
      geometry, including the narrow anterior valve, poses a serious challenge to
      efficient drug delivery. This barrier, plus the inherent limitations of
      traditional nasal delivery mechanisms, has precluded achievement of the full
      potential of nasal delivery. Breath Powered bi-directional delivery, a simple but
      novel nasal delivery mechanism, overcomes these barriers. This innovative
      mechanism has now been applied to the delivery of sumatriptan. Multiple studies
      of drug deposition, including comparisons of traditional nasal sprays to Breath
      Powered delivery, demonstrate significantly improved deposition to superior and
      posterior intranasal target sites beyond the nasal valve. Pharmacokinetic studies
      in both healthy subjects and migraineurs suggest that improved deposition of
      sumatriptan translates into improved absorption and pharmacokinetics.
      Importantly, the absorption profile is shifted toward a more pronounced early
      peak, representing nasal absorption, with a reduced late peak, representing
      predominantly gastrointestinal (GI) absorption. The flattening and "spreading
      out" of the GI peak appears more pronounced in migraine sufferers than healthy
      volunteers, likely reflecting impaired GI absorption described in migraineurs. In
      replicated clinical trials, Breath Powered delivery of low-dose sumatriptan was
      well accepted and well tolerated by patients, and onset of pain relief was faster
      than generally reported in previous trials with noninjectable triptans.
      Interestingly, Breath Powered delivery also allows for the potential of headache
      targeted medications to be better delivered to the trigeminal nerve and the
      sphenopalatine ganglion, potentially improving treatment of various types of
      headache. In brief, Breath Powered bi-directional intranasal delivery offers a
      new and more efficient mechanism for nasal drug delivery, providing an attractive
      option for improved treatment of headaches by enabling or enhancing the benefits
      of current and future headache therapies. 

PMID- 24024606
TI  - Requirement of epithelial integrin-linked kinase for facilitation of Citrobacter
      rodentium-induced colitis.
AB  - BACKGROUND: Integrin-linked kinase (ILK) is a serine-threonine kinase that
      transduces extracellular matrix-related cues into intracellular signals, with
      fundamental roles in cell motility, development and cancer. Recently ILK been
      shown to have an important role in bacterial epithelial cell attachment, through
      ILK-bacterial OspE binding. Here we report on the role of epithelial derived ILK
      in response to Citrobacter rodentium infection. METHODS: C. rodentium was
      administered to both control and intestinal epithelial cell ILK knockout mice.
      Histological inflammatory scores were assessed, and cytokines measured by ELISA
      as well as RT-PCR, in mouse colons. Bacterial colonization was determined by
      plating homogenates onto MacConkey agar, and immunofluorescence microscopy
      performed using anti-LPS and anti-Tir antibodies. RESULTS: ILK-ko mice exhibited
      reduced weight loss at 15 days post-infection (p < 0.01) and demonstrated reduced
      histological inflammatory scores (p < 0.01), reduced CCL2 and pro-inflammatory
      cytokines. This was not due to reduced colonization, but was associated with an
      altered pattern of C. rodentium bacterial migration. Attenuated fibronectin
      expression was found in the ILK-ko mice. C. rodentium exposure was shown to
      increase ILK expression in cell lines, and in murine epithelium in vivo. In ILK
      ko mice reduced activation of ser473Akt and reduced crypt proliferation, together
      with reduced cyclin D1 expression were observed. CONCLUSIONS: ILK influences the
      host response to C. rodentium -induced infection, independently of reduced
      colonization in the ILK knockout mice. The reduced inflammation and dramatically
      attenuated hyperplastic cryptal response to infection in this group, are at least
      in part the result of, the reduction in CCL2 and cyclin D1 expression
      respectively.

PMID- 24024607
TI  - Mercury methylation by novel microorganisms from new environments.
AB  - Microbial mercury (Hg) methylation transforms a toxic trace metal into the highly
      bioaccumulated neurotoxin methylmercury (MeHg). The lack of a genetic marker for
      microbial MeHg production has prevented a clear understanding of Hg-methylating
      organism distribution in nature. Recently, a specific gene cluster (hgcAB) was
      linked to Hg methylation in two bacteria.1 Here we test if the presence of hgcAB
      orthologues is a reliable predictor of Hg methylation capability in
      microorganisms, a necessary confirmation for the development of molecular probes
      for Hg-methylation in nature. Although hgcAB orthologues are rare among all
      available microbial genomes, organisms are much more phylogenetically and
      environmentally diverse than previously thought. By directly measuring MeHg
      production in several bacterial and archaeal strains encoding hgcAB, we confirmed
      that possessing hgcAB predicts Hg methylation capability. For the first time, we
      demonstrated Hg methylation in a number of species other than sulfate- (SRB) and
      iron- (FeRB) reducing bacteria, including methanogens, and syntrophic,
      acetogenic, and fermentative Firmicutes. Several of these species occupy novel
      environmental niches for Hg methylation, including methanogenic habitats such as
      rice paddies, the animal gut, and extremes of pH and salinity. Identification of
      these organisms as Hg methylators now links methylation to discrete gene markers
      in microbial communities. 

PMID- 24024609
TI  - Systems Biology and Ratio-Based, Real-Time Disease Surveillance.
AB  - Most infectious disease surveillance methods are not well fit for early
      detection. To address such limitation, here we evaluated a ratio- and Systems
      Biology-based method that does not require prior knowledge on the identity of an
      infective agent. Using a reference group of birds experimentally infected with
      West Nile virus (WNV) and a problem group of unknown health status (except that
      they were WNV-negative and displayed inflammation), both groups were followed
      over 22 days and tested with a system that analyses blood leucocyte ratios. To
      test the ability of the method to discriminate small data sets, both the
      reference group (n = 5) and the problem group (n = 4) were small. The questions
      of interest were as follows: (i) whether individuals presenting inflammation
      (disease-positive or D+) can be distinguished from non-inflamed (disease-negative
      or D-) birds, (ii) whether two or more D+ stages can be detected and (iii)
      whether sample size influences detection. Within the problem group, the ratio
      based method distinguished the following: (i) three (one D- and two D+) data
      classes; (ii) two (early and late) inflammatory stages; (iii) fast versus regular
      or slow responders; and (iv) individuals that recovered from those that remained
      inflamed. Because ratios differed in larger magnitudes (up to 48 times larger)
      than percentages, it is suggested that data patterns are likely to be recognized
      when disease surveillance methods are designed to measure inflammation and
      utilize ratios.

PMID- 24024608
TI  - Fever is associated with delayed ventilator liberation in acute lung injury.
AB  - BACKGROUND: Acute lung injury (ALI) is characterized by inflammation, leukocyte
      activation, neutrophil recruitment, endothelial dysfunction, and epithelial
      injury, which are all affected by fever. Fever is common in the intensive care
      unit, but the relationship between fever and outcomes in ALI has not yet been
      studied. We evaluated the association of temperature dysregulation with time to
      ventilator liberation, ventilator-free days, and in-hospital mortality. METHODS:
      Analysis of a prospective cohort study, which recruited consecutive patients with
      ALI from 13 intensive care units at four hospitals in Baltimore, Maryland. The
      relationship of fever and hypothermia with ventilator liberation was assessed
      with a Cox proportional hazards model. We evaluated the association of
      temperature during the first 3 days after ALI with ventilator-free days, using
      multivariable linear regression models, and the association with mortality was
      evaluated by robust Poisson regression. MEASUREMENTS AND MAIN RESULTS: Of 450
      patients, only 12% were normothermic during the first 3 days after ALI onset.
      During the first week post-ALI, each additional day of fever resulted in a 33%
      reduction in the likelihood of successful ventilator liberation (95% confidence
      interval [CI] for adjusted hazard ratio, 0.57 to 0.78; P < 0.001). Hypothermia
      was independently associated with decreased ventilator-free days (hypothermia
      during each of the first 3 d: reduction of 5.58 d, 95% CI: -9.04 to -2.13; P =
      0.002) and increased mortality (hypothermia during each of the first 3 d:
      relative risk, 1.68; 95% CI, 1.06 to 2.66; P = 0.03). CONCLUSIONS: Fever and
      hypothermia are associated with worse clinical outcomes in ALI, with fever being
      independently associated with delayed ventilator liberation.

PMID- 24024610
TI  - Management algorithms for primary angle closure disease: comment.

PMID- 24024611
TI  - Preferential phenotypic association linked with cooperation in paper wasps.
AB  - Animals can influence their social environment by preferentially associating with
      certain conspecifics. Such preferential association has gained increasing
      theoretical attention, as it may influence social evolution and population
      dynamics. However, relatively little empirical work has examined the occurrence
      of preferential association and its effects on cooperative group formation. Here,
      we test the factors associated with cooperative group formation in Polistes
      dominulus nest-founding queen wasps. P. dominulus are a good system to study
      preferential association, as foundresses can nest alone or in groups and group
      membership is flexible. We found that both social and environmental factors were
      associated with partner choice. First, facial patterns were associated with
      cooperation. Wasps with more similar facial patterns were more likely to
      cooperate than wasps with less similar facial patterns. This preferential
      phenotypic association fits the theoretical criteria for the evolution of tag
      based cooperation. Season was also associated with cooperation; wasps on early
      season nests were more likely to cooperate than wasps on late-season nests. High
      levels of aggression by nest owners during initial interactions were also
      correlated with lower probabilities of subsequent cooperation, suggesting that
      nest owners have some control over group membership. Other factors including body
      weight, weight similarity and nest productivity were not linked with cooperation.
      Overall, multiple factors influence cooperation in paper wasps, including facial
      pattern similarity. The occurrence of preferential phenotypic association in
      paper wasps is quite interesting and may influence the evolution of cooperation
      and population divergence in this group. 

PMID- 24024612
TI  - Single-cell PCR analysis of murine embryonic stem cells cultured on different
      substrates highlights heterogeneous expression of stem cell markers.
AB  - BACKGROUND INFORMATION: In the last few years, recent evidence has revealed that
      inside an apparently homogeneous cell population there indeed appears to be
      heterogeneity. This is particularly true for embryonic stem (ES) cells where
      markers of pluripotency are dynamically expressed within the single cells. In
      this work, we have designed and tested a new set of primers for multiplex PCR
      detection of pluripotency markers expression, and have applied it to perform a
      single-cell analysis in murine ES cells cultured on three different substrates
      that could play an important role in controlling cell behaviour and fate: (i)
      mouse embryonic fibroblast (MEF) feeder layer, as the standard method for ES
      cells culture; (ii) Matrigel coating; (iii) micropatterned hydrogel. RESULTS:
      Compared with population analysis, using a single-cell approach, we were able to
      evaluate not only the number of cells that maintained the expression of a
      specific gene but, most importantly, how many cells co-expressed different
      markers. We found that micropatterned hydrogel seems to represent a good
      alternative to MEF, as the expression of stemness markers is better preserved
      than in Matrigel culture. CONCLUSIONS: This single-cell assay allows for the
      assessment of the stemness maintenance at a single-cell level in terms of gene
      expression profile, and can be applied in stem cell research to characterise
      freshly isolated and cultured cells, or to standardise, for instance, the method
      of culture closely linked to the transcriptional activity and the differentiation
      potential.

PMID- 24024613
TI  - DprE1, a new taxonomic marker in mycobacteria.
AB  - Among the species of the Mycobacterium genus, more than 50 have been recognized
      as human pathogens. In spite of the different diseases caused by mycobacteria,
      the interspecies genetic similarity ranges from 94% to 100%, and for some
      species, this value is higher than in other bacteria. Consequently, it is
      important to understand the relationships existing among mycobacterial species.
      In this context, the possibility to use Mycobacterium tuberculosis dprE1 gene as
      new phylogenetic/taxonomic marker has been explored. The dprE1 gene codes for the
      target of benzothiazinones, belonging to a very promising class of antitubercular
      drugs. Mutations in cysteine 387 of DprE1 are responsible for benzothiazinone
      resistance. The DprE1 tree, obtained with 73 amino acid sequences of
      mycobacterial species, revealed that concerning the benzothiazinone
      sensitivity/resistance, it is possible to discriminate two clusters. To validate
      it, a concatamer obtained from the amino acid sequences of nine mycobacterial
      housekeeping genes was performed. The concatamer revealed that there is no
      separation between the benzothiazinone-susceptible and benzothiazinone-resistant
      species; consequently, this parameter is not linked to the phylogeny. DprE1 tree
      might represent a good taxonomic marker for the assignment of a mycobacterial
      isolate to a species. Moreover, the concatamer represents a good reference
      phylogeny for the Mycobacterium genus. 

PMID- 24024614
TI  - Seasonality of oestrus, ovulation and ovulation rate of Sicilo-Sarde sheep.
AB  - This study aimed to investigate monthly changes in oestrus and ovulatory activity
      of Sicilo-Sarde sheep. Experimental animals comprised 25 adult and 10 maiden ewes
      at the start of the experiment. For 12 consecutive months (September-August), the
      females were exposed to natural photoperiod and permanently kept in presence of
      seven aproned rams. Oestrus was checked daily and ovarian activity was monitored
      by monthly endoscopies during the last week of each month. Ovulation rate for a
      particular month was assessed as the sum of corpora lutea or corpora albicans
      present on both ovaries at the time of endoscopy. Proportions of ewes observed in
      oestrus at least once a month were lowest in March (24.3%) and highest in June
      and October (100%). They tended (p < 0.06) to be different according to age,
      dropping during summer from a common value of 100% in June to 85.7% and 90% in
      July and then to 57.1% and 70% in August for, respectively, the Adults and Maiden
      females. Overall, the experimental period, 92.5% and 83.8% of Adult and Maiden
      ewes ovulated at least once per month (p < 0.01) respectively. Least proportions
      ovulating, attained 60% and 30% in April for, respectively, Adult and Maiden ewes
      before peaking up at 100% again in May (p < 0.05). Mean (+/-SD) ovulation rate of
      Sicilo-Sarde sheep is 1.40 +/- 0.503. Adult females had a higher (p < 0.001)
      ovulation rate than Maiden sheep with respective average values of 1.51 +/- 0.516
      and 1.16 +/- 0.373. It varied little between months and decreased in Adults from
      a maximum value of 1.95 in October to a minimum value of 1.16 in April. It is
      concluded that benchmarking seasonal variations of reproductive activity in
      Sicilo-Sarde breed would be valuable in designing improved management calendars
      for this breed. 

PMID- 24024615
TI  - Density functional predictions of antioxidant activity and UV spectral features
      of nasutin A, isonasutin, ellagic acid, and one of its possible derivatives.
AB  - The antioxidant ability of ellagic acid and some of its derivatives was explored
      at density functional level of theory within the framework of the following three
      different reaction mechanisms: hydrogen atom transfer (HAT), electron transfer
      followed by proton transfer (SET-PT), and sequential proton loss electron
      transfer (SPLET). Computations were performed in gas phase and in both water and
      methanol media. Results show that the HAT mechanism is preferred by this class of
      compounds in all environments, although, in principle, polar solvents should
      promote the SET-PT and SPLET mechanisms. Among the considered compounds, the
      derivative not yet experimentally characterized seems to be the most promising
      candidate as antioxidant. For a more detailed spectroscopic characterization and
      to help in the identification of these compounds, the simulated UV spectra of all
      investigated molecules were done by using the time-dependent formulation of
      density functional theory (TDDFT). 

PMID- 24024616
TI  - Effects of essential amino acid deficiency: down-regulation of KCC2 and the GABAA
      receptor; disinhibition in the anterior piriform cortex.
AB  - The anterior piriform cortex (APC) is activated by, and is the brain area most
      sensitive to, essential (indispensable) amino acid (IAA) deficiency. The APC is
      required for the rapid (20 min) behavioral rejection of IAA deficient diets and
      increased foraging, both crucial adaptive functions supporting IAA homeostasis in
      omnivores. The biochemical mechanisms signaling IAA deficiency in the APC block
      initiation of translation in protein synthesis via uncharged tRNA and the general
      amino acid control kinase, general control nonderepressing kinase 2. Yet, how
      inhibition of protein synthesis activates the APC is unknown. The neuronal K(+)
      Cl(-) cotransporter, neural potassium chloride co-transporter (KCC2), and GABAA
      receptors are essential inhibitory elements in the APC with short plasmalemmal
      half-lives that maintain control in this highly excitable circuitry. After a
      single IAA deficient meal both proteins were reduced (vs. basal diet controls) in
      western blots of APC (but not neocortex or cerebellum) and in
      immunohistochemistry of APC. Furthermore, electrophysiological analyses support
      loss of inhibitory elements such as the GABAA receptor in this model. As the
      crucial inhibitory function of the GABAA receptor depends on KCC2 and the Cl(-)
      transmembrane gradient it establishes, these results suggest that loss of such
      inhibitory elements contributes to disinhibition of the APC in IAA deficiency.
      The circuitry of the anterior piriform cortex (APC) is finely balanced between
      excitatory (glutamate, +) and inhibitory (GABA, -) transmission. GABAA receptors
      use Cl(-), requiring the neural potassium chloride co-transporter (KCC2). Both
      are rapidly turning-over proteins, dependent on protein synthesis for repletion.
      In IAA (indispensable amino acid) deficiency, within 20 min, blockade of protein
      synthesis prevents restoration of these inhibitors; they are diminished;
      disinhibition ensues. GCN2 = general control non-derepressing kinase 2, eIF2alpha
      = alpha-subunit of the eukaryotic initiation factor 2.

PMID- 24024618
TI  - Pennsylvania police officer trained for mental illness crises.

PMID- 24024617
TI  - Characterizing the secondary protein structure of black widow dragline silk using
      solid-state NMR and X-ray diffraction.
AB  - This study provides a detailed secondary structural characterization of major
      ampullate dragline silk from Latrodectus hesperus (black widow) spiders. X-ray
      diffraction results show that the structure of black widow major ampullate silk
      fibers is comprised of stacked beta-sheet nanocrystallites oriented parallel to
      the fiber axis and an amorphous region with oriented (anisotropic) and isotropic
      components. The combination of two-dimensional (2D) (13)C-(13)C through-space and
      through-bond solid-state NMR experiments provide chemical shifts that are used to
      determine detailed information about the amino acid motif secondary structure in
      black widow spider dragline silk. Individual amino acids are incorporated into
      different repetitive motifs that make up the majority of this protein-based
      biopolymer. From the solid-state NMR measurements, we assign distinct secondary
      conformations to each repetitive amino acid motif and, hence, to the amino acids
      that make up the motifs. Specifically, alanine is incorporated in beta-sheet
      (poly(Alan) and poly(Gly-Ala)), 3(1)-helix (poly(Gly-Gly-Xaa), and alpha-helix
      (poly(Gln-Gln-Ala-Tyr)) components. Glycine is determined to be in beta-sheet
      (poly(Gly-Ala)) and 3(1)-helical (poly(Gly-Gly-X(aa))) regions, while serine is
      present in beta-sheet (poly(Gly-Ala-Ser)), 3(1)-helix (poly(Gly-Gly-Ser)), and
      beta-turn (poly(Gly-Pro-Ser)) structures. These various motif-specific secondary
      structural elements are quantitatively correlated to the primary amino acid
      sequence of major ampullate spidroin 1 and 2 (MaSp1 and MaSp2) and are shown to
      form a self-consistent model for black widow dragline silk.

PMID- 24024619
TI  - Students' impulsive behavior tempered with breathing-based program.

PMID- 24024620
TI  - Verbal abuse on the job makes RNs seek new employment.

PMID- 24024624
TI  - Thiocyanate-free ruthenium(II) sensitizer with a pyrid-2-yltetrazolate ligand for
      dye-sensitized solar cells.
AB  - The synthesis of the new complex [Ru(Tetrazpy)(dcbpy)2]Cl is reported, along with
      its spectroscopical, electrochemical, and theoretical characterization. The first
      dye-sensitized solar cell device with this complex has been prepared, leading to
      a 3% of conversion efficiency, promising data considering the simplicity of the
      Tetrazpy ligand. 

PMID- 24024625
TI  - Inactivation of pathogenic dermatophytes by ultraviolet irradiation in swimming
      pool thermal water.
AB  - The effect of ultraviolet (UV) radiation from low-pressure mercury lamp against
      some pathogenic dermatophytes species such as Epidermophyton floccosum,
      Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton schoenleinii,
      Trichophyton tonsurans and Trichophyton violaceum suspended in thermal water was
      evaluated in laboratory-scale condition at various times. The main results showed
      that within 120 s of exposure, all species of dermatophytes are completely
      inactivated, which was evidenced by the absence of fungal regrowth, while after
      60 s only T. tonsurans was recovered, with a reduction of 3.28 log. Shorter
      exposure times were not enough to completely inactivate all dermatophytes
      species. The samples treated with UV radiation for 120 s did not give evidence of
      fungal regrowth indicating that this disinfectant action is persistent over time.
      In conclusion, UV radiation can be proposed to reduce the risk of infection by
      dermatophytes eventually present in swimming pools that use thermal water.

PMID- 24024626
TI  - Estimating trophic levels and trophic magnification factors using Bayesian
      inference.
AB  - Food web biomagnification is increasingly assessed by estimating trophic
      magnification factors (TMF) where solvent (often lipid) normalized contaminant
      concentration is regressed onto the trophic level, and TMFs are represented by
      the slope of the relationship. In TMF regressions, the uncertainty in the
      contaminant concentrations is appreciated, whereas the trophic levels are assumed
      independent and not associated with variability or uncertainty pertaining to e.g.
      quantification. In reality, the trophic levels may vary due to measurement error
      in stable isotopes of nitrogen (delta(15)N) of each sample, in delta(15)N in
      selected reference baseline trophic level, and in the enrichment factor of
      delta(15)N between two trophic levels (DeltaN), which are all needed to calculate
      trophic levels. The present study used a Markov Chain Monte Carlo method, with
      knowledge about the food web structure, which resulted in a dramatic increase in
      the precision in the TMF estimates. This also lead to a better understanding of
      the uncertainties in bioaccumulation measures; instead of using point estimates
      of TMF, the uncertainty can be quantified (i.e., TMF >1, namely positive
      biomagnification, with an estimated X % probability). 

PMID- 24024627
TI  - Drug safety evaluation of olanzapine pamoate.
AB  - INTRODUCTION: Olanzapine pamoate is one of three second-generation antipsychotics
      available as depot medication. While non-adherence is a major problem in the
      treatment of schizophrenia, olanzapine pamoate can improve adherence, though its
      use is limited by its safety profile. AREAS COVERED: The review covers data on
      efficacy with a focus on tolerability and safety of olanzapine pamoate using the
      known databases including PubMed, Psychinfo and Embase using keywords. Relevant
      websites were also reviewed. EXPERT OPINION: Olanzapine is an efficacious
      antipsychotic that can be used in its oral and depot formula (olanzapine pamoate)
      for the treatment of patients with schizophrenia. It has demonstrated superiority
      over conventional and some other atypical antipsychotics, with both formulas
      having comparable low rates of motor side effects. The side effects on body
      weight and glucose homeostasis are also similar in both formulas and limit its
      use. The only clear difference regarding side effects is 'the risk that 0.07% of
      injections in preclinical trials have led to a post-injection delirium/sedation
      syndrome event which requires a risk management plan'. Especially in outpatients
      this could cause inconveniences that should be overcome by offering, for example,
      psychological therapies or psychoeducation to effectively use the time when
      patients have to remain in the healthcare facilities.

PMID- 24024628
TI  - Synergistic effect of carbon nanofiber/nanotube composite catalyst on carbon felt
      electrode for high-performance all-vanadium redox flow battery.
AB  - Carbon nanofiber/nanotube (CNF/CNT) composite catalysts grown on carbon felt
      (CF), prepared from a simple way involving the thermal decomposition of acetylene
      gas over Ni catalysts, are studied as electrode materials in a vanadium redox
      flow battery. The electrode with the composite catalyst prepared at 700  degrees
      C (denoted as CNF/CNT-700) demonstrates the best electrocatalytic properties
      toward the V(2+)/V(3+) and VO(2+)/VO2(+) redox couples among the samples prepared
      at 500, 600, 700, and 800  degrees C. Moreover, this composite electrode in the
      full cell exhibits substantially improved discharge capacity and energy
      efficiency by ~64% and by ~25% at 40 mA.cm(-2) and 100 mA.cm(-2), respectively,
      compared to untreated CF electrode. This outstanding performance is due to the
      enhanced surface defect sites of exposed edge plane in CNF and a fast electron
      transfer rate of in-plane side wall of the CNT.

PMID- 24024629
TI  - Infrared spectra of the 1-pyridinium (C5H5NH+) cation and pyridinyl (C5H5NH and 4
      C5H6N) radicals isolated in solid para-hydrogen.
AB  - Protonated pyridine and its neutral counterparts (C5H6N) are important
      intermediates in organic and biological reactions and in the atmosphere. We have
      recorded the IR absorption spectra of the 1-pyridinium (C5H5NH(+)) cation, 1
      pyridinyl (C5H5NH), and 4-pyridinyl (4-C5H6N) produced on electron bombardment
      during matrix deposition of a mixture of pyridine (C5H5N) and p-H2 at 3.2 K; all
      spectra were previously unreported. The IR features of C5H5NH(+) diminished in
      intensity after the matrix was maintained in darkness for 15 h, whereas those of
      C5H5NH and 4-C5H6N radicals increased. Irradiation of this matrix with light at
      365 nm diminished lines of C5H5NH(+) and C5H5NH but enhanced lines of 4-C5H6N
      slightly, whereas irradiation at 405 nm diminished lines of 4-C5H6N
      significantly. Observed wavenumbers and relative intensities of these species
      agree satisfactorily with the anharmonic vibrational wavenumbers and IR
      intensities predicted with the B3LYP/6-31++G(d,p) method. Assignments of C5H5NH
      and 4-C5H6N radicals were further supported by the observation of similar spectra
      when a Cl2/C5H5N/p-H2 matrix was irradiated first at 365 nm and then with IR
      light to generate H atoms to induce the H + C5H5N reaction. 

PMID- 24024630
TI  - Population-level effects of clinical immunity to malaria.
AB  - BACKGROUND: Despite a resurgence in control efforts, malaria remains a serious
      public-health problem, causing millions of deaths each year. One factor that
      complicates malaria-control efforts is clinical immunity, the acquired immune
      response that protects individuals from symptoms despite the presence of
      parasites. Clinical immunity protects individuals against disease, but its
      effects at the population level are complex. It has been previously suggested
      that under certain circumstances, malaria is bistable: it can persist, if
      established, in areas where it would not be able to invade. This phenomenon has
      important implications for control: in areas where malaria is bistable, if
      malaria could be eliminated until immunity wanes, it would not be able to re
      invade. METHODS: Here, we formulate an analytically tractable, dynamical model of
      malaria transmission to explore the possibility that clinical immunity can lead
      to bistable malaria dynamics. We summarize what is known and unknown about the
      parameters underlying this simple model, and solve the model to find a criterion
      that determines under which conditions we expect bistability to occur. RESULTS:
      We show that bistability can only occur when clinically immune individuals are
      more "effective" at transmitting malaria than naive individuals are. We show how
      this "effectiveness" includes susceptibility, ability to transmit, and duration
      of infectiousness. We also show that the amount of extra effectiveness necessary
      depends on the ratio between the duration of infectiousness and the time scale at
      which immunity is lost. Thus, if the duration of immunity is long, even a small
      amount of extra transmission effectiveness by clinically immune individuals could
      lead to bistability. CONCLUSIONS: We demonstrate a simple, plausible mechanism by
      which clinical immunity may be causing bistability in human malaria transmission.
      We suggest that simple summary parameters--in particular, the relative
      transmission effectiveness of clinically immune individuals and the time scale at
      which clinical immunity is lost--are key to determining where and whether
      bistability is happening. We hope these findings will guide future efforts to
      measure transmission parameters and to guide malaria control efforts.

PMID- 24024631
TI  - Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice
      by suggesting severity strata derived using anchor-based methods.
AB  - BACKGROUND: The Patient-Oriented Eczema Measure (POEM) is a validated, patient
      derived assessment measure for monitoring atopic eczema severity, although
      further information on how different POEM scores translate into disease severity
      categories is needed for clinical trials, epidemiological research and audit.
      OBJECTIVES: We sought to determine the relationship between Patient-Oriented
      Eczema Measure (POEM) scores (range 0-28) and two Global Questions (GQ1 and 2)
      concerning patients'/parents' views of the overall severity of their/their
      child's atopic eczema, in order to stratify POEM scores into five severity bands.
      METHODS: POEM scores and GQs were completed by 300 patients from general practice
      and 700 patients from dermatology outpatient clinics, including 300 adults aged
      >= 16 years and 700 children. RESULTS: The mean POEM score was 13.6 (range 0-28),
      and standard deviation (SD) was 7.2. Mean GQ1/GQ2 scores were 2.1/2.1,
      respectively (range 0-4 and SD 1.1 for both). The mean, mode and median of the GQ
      scores for each POEM score were used to devise possible POEM bandings. The
      proposed banding for POEM scores are: 0-2 (clear/almost clear); 3-7 (mild); 8-16
      (moderate); 17-24 (severe); 25-28 (very severe), kappa coefficient 0.46.
      CONCLUSIONS: Severity banding of the POEM will allow more clinically meaningful
      use in everyday clinical practice and as a core outcome measure in future atopic
      eczema research.

PMID- 24024632
TI  - Fifty years fused to lac.
AB  - I recount the history of how I became interested in the use of gene fusions for
      studying biological problems. Initially, selections for mutations that would
      restore function to an inactivated lac operon unexpectedly yielded fusions in
      which lac was expressed from the controlling elements of upstream genes.
      Subsequently, by chance, I generated strains in which the lac operon was
      transposed from its normal position on the chromosome to a position close to the
      trp operon, thus facilitating sets of useful fusions of the two operons. The
      development of a more generalized technique for obtaining fusions by my student
      Malcolm Casadaban opened up a much broader set of biological problems that could
      be approached with fusions. Work on these problems included the study of protein
      translocation across membranes, the analysis of membrane protein topology, and
      the discovery of the pathway of electron transfer that leads to disulfide bond
      formation in proteins. 

PMID- 24024633
TI  - Electrophysiology of bacteria.
AB  - Bacteria secrete and harbor in their membranes a number of pore-forming proteins.
      Some of these are bona fide ion channels that may respond to changes in membrane
      tension, voltage, or pH. Others may be large translocons used for the secretion
      of folded or unfolded polypeptide substrates. Additionally, many secreted toxins
      insert into target cell membranes and form pores that either collapse membrane
      electrochemical gradients or provide conduits for the delivery of virulence
      factors. In all cases, electrophysiological approaches have yielded much progress
      in past decades in understanding the functional mechanisms of these pores. By
      monitoring the changes in current due to ion flow through the pores, these
      techniques are used as high-resolution tools to gather detailed information on
      the kinetic and permeation properties of these proteins, including those whose
      physiological role is not ion flux. This review highlights some of the
      electrophysiological studies that have advanced the field of transport by pore
      forming proteins of bacterial origin. 

PMID- 24024635
TI  - An inquiry into the molecular basis of HSV latency and reactivation.
AB  - Herpes simplex virus (HSV) evolved an elegant strategy that enables the virus to
      impact a large fraction of the human population. The virus replicates at the
      portal of entry (mouth, genitals) and concurrently it is transported retrograde
      to sensory neurons. In sensory neurons it establishes a silent (latent)
      infection. A variety of stimuli can reactivate the virus. The reactivated virus
      is transmitted anterograde to a site at the portal of entry for transmission by
      physical contact between infected and uninfected tissues to other individuals.
      The central issue is how a virus that vigorously replicates and successfully
      blocks the innate immune defenses of the host at the portal of entry into the
      body remains silent in sensory neurons. The presentation focuses on three key
      issues: (a) current assessment of the impact of HSV on human health, (b) the
      mechanisms by which the virus overcomes a key host defense mechanism at the
      portal of entry into the body and yet is silenced in latently infected neurons,
      and (c) the mechanisms by which the virus reactivates. 

PMID- 24024634
TI  - Wall teichoic acids of gram-positive bacteria.
AB  - The peptidoglycan layers of many gram-positive bacteria are densely
      functionalized with anionic glycopolymers known as wall teichoic acids (WTAs).
      These polymers play crucial roles in cell shape determination, regulation of cell
      division, and other fundamental aspects of gram-positive bacterial physiology.
      Additionally, WTAs are important in pathogenesis and play key roles in antibiotic
      resistance. We provide an overview of WTA structure and biosynthesis, review
      recent studies on the biological roles of these polymers, and highlight remaining
      questions. We also discuss prospects for exploiting WTA biosynthesis as a target
      for new therapies to overcome resistant infections. 

PMID- 24024636
TI  - Fusarium pathogenomics.
AB  - Fusarium is a genus of filamentous fungi that contains many agronomically
      important plant pathogens, mycotoxin producers, and opportunistic human
      pathogens. Comparative analyses have revealed that the Fusarium genome is
      compartmentalized into regions responsible for primary metabolism and
      reproduction (core genome), and pathogen virulence, host specialization, and
      possibly other functions (adaptive genome). Genes involved in virulence and host
      specialization are located on pathogenicity chromosomes within strains pathogenic
      to tomato (Fusarium oxysporum f. sp. lycopersici) and pea (Fusarium 'solani' f.
      sp. pisi). The experimental transfer of pathogenicity chromosomes from F.
      oxysporum f. sp. lycopersici into a nonpathogen transformed the latter into a
      tomato pathogen. Thus, horizontal transfer may explain the polyphyletic origins
      of host specificity within the genus. Additional genome-scale comparative and
      functional studies are needed to elucidate the evolution and diversity of
      pathogenicity mechanisms, which may help inform novel disease management
      strategies against fusarial pathogens. 

PMID- 24024638
TI  - The wonderful world of archaeal viruses.
AB  - This review presents a personal account of research on archaeal viruses and
      describes many new viral species and families, demonstrating that viruses of
      Archaea constitute a distinctive part of the virosphere and display morphotypes
      that are not associated with the other two domains of life, Bacteria and Eukarya.
      I focus primarily on viruses that infect hyperthermophilic members of the phylum
      Crenarchaeota. These viruses' distinctiveness extends from their morphotypes to
      their genome sequences and the structures of the proteins they encode. Moreover,
      the mechanisms underlying the interactions of these viruses with their hosts also
      have unique features. Studies of archaeal viruses provide new perspectives
      concerning the nature, diversity, and evolution of virus-host interactions.
      Considering these studies, I associate the distinctions between bacterial and
      archaeal viruses with the fundamental differences in the envelope compositions of
      their host cells. 

PMID- 24024639
TI  - A paradigm for endosymbiotic life: cell differentiation of Rhizobium bacteria
      provoked by host plant factors.
AB  - Symbiosis between Rhizobium bacteria and legumes leads to the formation of the
      root nodule. The endosymbiotic bacteria reside in polyploid host cells as
      membrane-surrounded vesicles where they reduce atmospheric nitrogen to support
      plant growth by supplying ammonia in exchange for carbon sources and energy. The
      morphology and physiology of endosymbionts, despite their common function, are
      highly divergent in different hosts. In galegoid plants, the endosymbionts are
      terminally differentiated, uncultivable polyploid cells, with remarkably
      elongated and even branched Y-shaped cells. Bacteroid differentiation is
      controlled by host peptides, many of which have antibacterial activity and
      require the bacterial function of BacA. Although the precise and combined action
      of several hundred host peptides and BacA has yet to be discovered, similarities,
      especially to certain insect-bacterium symbioses involving likewise host peptides
      for manipulation of endosymbionts, suggest convergent evolution. Rhizobium-legume
      symbiosis provides a rich source of information for understanding host-controlled
      endosymbiotic life in eukaryotic cells. 

PMID- 24024637
TI  - Experimental approaches for defining functional roles of microbes in the human
      gut.
AB  - The complex and intimate relationship between humans and their gut microbial
      communities is becoming less obscure, due in part to large-scale gut microbial
      genome-sequencing projects and culture-independent surveys of the composition and
      gene content of these communities. These studies build upon, and are complemented
      by, experimental efforts to define underlying mechanisms of host-microbe
      interactions in simplified model systems. This review highlights the intersection
      of these approaches. Experimental studies now leverage the advances in high
      throughput DNA sequencing that have driven the explosion of microbial genome and
      community profiling projects, and the loss-of-function and gain-of-function
      strategies long employed in model organisms are now being extended to microbial
      genes, species, and communities from the human gut. These developments promise to
      deepen our understanding of human gut host-microbiota relationships and are
      readily applicable to other host-associated and free-living microbial
      communities. 

PMID- 24024640
TI  - Role of Ca2+ in folding the tandem beta-sandwich extender domains of a bacterial
      ice-binding adhesin.
AB  - A Ca(2+) -dependent 1.5-MDa antifreeze protein present in an Antarctic Gram
      negative bacterium, Marinomonas primoryensis (MpAFP), has recently been
      reassessed as an ice-binding adhesin. The non-ice-binding region II (RII), one of
      five distinct domains in MpAFP, constitutes ~ 90% of the protein. RII consists of
      ~ 120 tandem copies of an identical 104-residue sequence. We used the Protein
      Homology/analogy Recognition Engine server to define the boundaries of a single
      104-residue RII construct (RII monomer). CD demonstrated that Ca(2+) is required
      for RII monomer folding, and that the monomer is fully structured at a Ca(2+)
      /protein molar ratio of 10 : 1. The crystal structure of the RII monomer was
      solved to a resolution of 1.35 A by single-wavelength anomalous dispersion and
      molecular replacement methods with Ca(2+) as the heavy atom to obtain phase
      information. The RII monomer folds as a Ca(2+) -bound immunoglobulin-like beta
      sandwich. Ca(2+) ions are coordinated at the interfaces between each RII monomer
      and its symmetry-related molecules, suggesting that these ions may be involved in
      the stabilization of the tandemly repeated RII. We hypothesize that > 600 Ca(2+)
      ions help to rigidify the chain of 104-residue repeats in order to project the
      ice-binding domain of MpAFP away from the bacterial cell surface. The proposed
      role of RII is to help the strictly aerobic bacterium bind surface ice in an
      Antarctic lake for better access to oxygen and nutrients. This work may give
      insights into other bacterial proteins that resemble MpAFP, especially those of
      the large repeats-in-toxin family that have been characterized as adhesins
      exported via the type I secretion pathway.

PMID- 24024642
TI  - Recent advances in assistive technology and engineering (RAATE)--a UK
      perspective.

PMID- 24024641
TI  - Predicting expected progeny difference for marbling score in Angus cattle using
      artificial neural networks and Bayesian regression models.
AB  - BACKGROUND: Artificial neural networks (ANN) mimic the function of the human
      brain and are capable of performing massively parallel computations for data
      processing and knowledge representation. ANN can capture nonlinear relationships
      between predictors and responses and can adaptively learn complex functional
      forms, in particular, for situations where conventional regression models are
      ineffective. In a previous study, ANN with Bayesian regularization outperformed a
      benchmark linear model when predicting milk yield in dairy cattle or grain yield
      of wheat. Although breeding values rely on the assumption of additive
      inheritance, the predictive capabilities of ANN are of interest from the
      perspective of their potential to increase the accuracy of prediction of
      molecular breeding values used for genomic selection. This motivated the present
      study, in which the aim was to investigate the accuracy of ANN when predicting
      the expected progeny difference (EPD) of marbling score in Angus cattle. Various
      ANN architectures were explored, which involved two training algorithms, two
      types of activation functions, and from 1 to 4 neurons in hidden layers. For
      comparison, BayesCpi models were used to select a subset of optimal markers
      (referred to as feature selection), under the assumption of additive inheritance,
      and then the marker effects were estimated using BayesCpi with pi set equal to
      zero. This procedure is referred to as BayesCpC and was implemented on a high
      throughput computing cluster. RESULTS: The ANN with Bayesian regularization
      method performed equally well for prediction of EPD as BayesCpC, based on
      prediction accuracy and sum of squared errors. With the 3K-SNP panel, for
      example, prediction accuracy was 0.776 using BayesCpC, and ranged from 0.776 to
      0.807 using BRANN. With the selected 700-SNP panel, prediction accuracy was 0.863
      for BayesCpC and ranged from 0.842 to 0.858 for BRANN. However, prediction
      accuracy for the ANN with scaled conjugate gradient back-propagation was lower,
      ranging from 0.653 to 0.689 with the 3K-SNP panel, and from 0.743 to 0.793 with
      the selected 700-SNP panel. CONCLUSIONS: ANN with Bayesian regularization
      performed as well as linear Bayesian regression models in predicting additive
      genetic values, supporting the idea that ANN are useful as universal
      approximators of functions of interest in breeding contexts.

PMID- 24024643
TI  - Respiratory bronchiolitis with fibrosis. High-resolution computed tomography
      findings and correlation with pathology.
AB  - BACKGROUND: Recent pathology studies report that the lungs of cigarette smokers
      may demonstrate small localized subpleural foci of interstitial fibrosis
      associated with emphysema. Pathologically, this lesion has been termed smoking
      related interstitial fibrosis, respiratory bronchiolitis-interstitial lung
      disease (ILD) with fibrosis, or airspace enlargement with fibrosis, but it is
      commonly misinterpreted on imaging and biopsy as a diffuse fibrosing interstitial
      pneumonia. The high-resolution computed tomography (HRCT) appearance of this
      process has not been defined. OBJECTIVES: We describe HRCT imaging of seven
      patients with this lesion present histologically. MEASUREMENTS AND MAIN RESULTS:
      HRCT features consisted of patchy areas of mild reticulation around predominantly
      subpleural upper/mid zone emphysematous changes in all cases, with variable
      patchy ground-glass change in six cases. Pathologically, there were distinctly
      circumscribed foci of dense, often hyalinized, interstitial fibrosis mixed with
      emphysema; variable numbers of smoker's macrophages were present in the
      airspaces. The fibrosis was confined to the subpleural regions. Three patients
      with follow-up information were clinically stable. CONCLUSIONS: These data
      suggest that a CT pattern of patchy areas of reticular changes about
      predominantly upper zone emphysematous spaces may be seen in smokers who do not
      have clinical evidence of a diffuse ILD. We propose that this lesion be called
      respiratory bronchiolitis with fibrosis (RBF) to avoid confusion with other forms
      of ILD. RBF probably accounts for some of the cases of ILD seen in large
      radiologic surveys of smokers. The pathology literature indicates that RBF either
      has no functional effects or at worst represents mild, usually nonprogressive
      disease, and hence separation from other, more serious, forms of ILD is
      important. Recognition of this lesion on imaging may obviate the need for lung
      biopsy.

PMID- 24024644
TI  - Management algorithms for primary angle closure disease: response.

PMID- 24024645
TI  - Quantification of relative proportions of intact cells in microbiological samples
      using the example of Cryptosporidium parvum oocysts.
AB  - The fast analysis of relative proportions of live and dead cells can be of great
      value whether for comparing inactivation efficiencies of different biocidal
      treatments or for monitoring organisms of interest in environmental samples. We
      introduce here a straightforward method to determine the percentage of intact
      cells based on treatment of samples with the viability dye propidium monoazide
      (PMA). PMA selectively enters membrane-damaged cells and suppresses their PCR
      detection through modification of their DNA. The study was performed using
      Cryptosporidium parvum oocysts as a model although the principle should be
      applicable to other organisms. Validation was performed with defined mixtures of
      live and heat-killed oocysts and by exposing oocysts to a heat stress gradient.
      The method correctly indicated increasingly lower proportions of intact cells
      with increasing temperatures. When comparing the loss of membrane integrity of UV
      killed (40 mJ cm(-2) ) oocysts during storage in nonsterile tap water, results
      suggested that integrity declines slowly (over weeks) and at a rate comparable to
      non-UV-exposed oocysts. For all experiments, the amplification of longer DNA
      sequences was found beneficial. In the UV experiment, longer amplicons revealed
      not only higher sensitivity in excluding membrane-damaged oocysts, but also in
      excluding DNA with UV-induced damage. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Whether in the context of microbial ecology or in an industrial context, many
      questions in microbiology are linked to microbial viability. As cultivation of
      micro-organisms can be long or may not be possible, fast methods to assess the
      numbers of live cells are in great demand. We present here a straightforward
      strategy to determine the relative proportions of intact cells. The PCR-based
      rapid method is expected to be useful where relative information is sufficient
      (e.g. for comparing the effect of different antimicrobial treatments on known
      numbers of micro-organisms) or when the presence of PCR inhibitors does not allow
      absolute quantification.

PMID- 24024646
TI  - Supramolecular glycolipid based on host-enhanced charge transfer interaction.
AB  - Supramolecular glycolipid has been fabricated based on ternary complex system,
      which is composed of naphthyl glucosamine (GlcNap), alkyl viologen (RV8), and
      cucurbit[8]uril (CB[8]). CB[8] plays a key role to connect the other two building
      blocks together, and the process is driven by host-enhanced charge transfer
      interaction. Compared with the classic glycolipids, supramolecular glycolipids
      display redox responsiveness. Supramolecular glycolipids are able to self
      assemble in water to form spherical aggregations, such as vesicle like structure.
      In addition, spherical aggregations can specifically interact with Concanavalin
      A, indicating that the carbohydrate groups are available on the surfaces of the
      aggregates. 

PMID- 24024647
TI  - Guided bone regeneration using acellular bovine pericardium in a rabbit
      mandibular model: in-vitro and in-vivo studies.
AB  - BACKGROUND AND OBJECTIVE: To investigate the feasibility of acellular bovine
      pericardium (BP) for guided bone regeneration (GBR) in vitro and in vivo. The
      success of GBR relies on the fact that various cellular components possess
      different migration rates into the defect site and that a barrier membrane plays
      a significant role in these processes. MATERIAL AND METHODS: BP membrane was
      isolated and decellularized using an enzymatic method. The microarchitecture,
      mechanical properties, cytotoxicity and cell chemotaxis properties of the
      acellular BP were evaluated in vitro, and the in-vivo efficacy of the acellular
      BP was also investigated in a rabbit mandibular model. RESULTS: The acellular BP
      membrane possessed an interconnected fibrous structure. Glutaraldehyde (GA)
      treatment was efficient for enhancement of the mechanical properties of the
      acellular BP bur and resulted in negligible cytotoxicity. After 16 wk,
      standardized osseous defects created in the rabbit mandible, and covered with
      acellular BP, were associated with an enhanced deposition of mineralized tissue
      when compared with defects left to spontaneous healing. CONCLUSION: GA-treated
      acellular BP is promising as a barrier membrane for GBR for further in-vivo and
      clinical studies.

PMID- 24024648
TI  - Fully validated LC-MS/MS assay for the simultaneous quantitation of
      coadministered therapeutic antibodies in cynomolgus monkey serum.
AB  - An LC-MS/MS assay was developed and fully validated for the simultaneous
      quantitation of two coadministered human monoclonal antibodies (mAbs), mAb-A and
      mAb-B of IgG4 subclass, in monkey serum. The total serum proteins were digested
      with trypsin at 50  degrees C for 30 min after methanol denaturation and
      precipitation, dithiothreitol reduction, and iodoacetamide alkylation. The
      tryptic peptides were chromatographically separated with a C18 column (2.1 * 100
      mm, 1.7 MUm) with mobile phases of 0.1% formic acid in water and acetonitrile.
      Four peptides, a unique peptide for each mAb and two confirmatory peptides from
      different antibody domains, were simultaneously quantified by LC-MS/MS in the
      multiple reaction-monitoring mode. Stable isotopically labeled peptides with
      flanking amino acids on C- and N-terminals were used as internal standards to
      minimize the variability during sample processing and detection. The LC-MS/MS
      assay showed lower limit of quantitation (LLOQ) at 5 MUg/mL for mAb-A and 25
      MUg/mL for mAb-B. The intra- and interassay precision (%CV) was within 10.0% and
      8.1%, respectively, and the accuracy (%Dev) was within +/-5.4% for all the
      peptides. Other validation parameters, including sensitivity, selectivity,
      dilution linearity, processing recovery and matrix effect, autosampler carryover,
      run size, stability, and data reproducibility, were all evaluated. The
      confirmatory peptides played a critical role in confirming quantitation accuracy
      and the integrity of the drugs in the study samples. The robustness of the LC
      MS/MS assay and the data agreement with the ligand binding data demonstrated that
      LC-MS/MS is a reliable and complementary approach for the quantitation of
      coadministered antibody drugs. 

PMID- 24024649
TI  - Spatial distributions and deposition chronology of short chain chlorinated
      paraffins in marine sediments across the Chinese Bohai and Yellow Seas.
AB  - As the most complex halogenated contaminants, short chain chlorinated paraffins
      (SCCPs) are scarcely reported in marine environments. In this work, a total of
      117 surficial sediment (0-3 cm) samples and two sediment cores were collected
      from the Chinese Bohai and Yellow Seas to systematically study the spatial and
      temporal trends of SCCPs at a large scale in the Chinese marine environment.
      Total SCCP concentrations in the surficial sediments were in the range of 14.5
      85.2 ng g(-1) (dry weight, d.w.) with an average level of 38.4 ng g(-1) d.w.
      Spatial distribution showed a decreasing trend with the distance from the coast
      to the open waters. Compositional pattern analysis suggested that C10 was the
      most predominant homologue group, followed by C11, C12, and C13 homologue groups.
      The concentrations of total SCCPs in sediment cores ranged from 11.6 to 94.7 ng
      g(-1) d.w. for YS1 and from 14.7 to 195.6 ng g(-1) d.w. for YS2, with sharp rise
      from the early 1950s to present based on (210)Pb dating technique. The historical
      records in cores correspond well to the production and usage changes of CPs in
      China. Multivariate regression statistics indicate TOC, latitude and longitude
      are the major factors influencing surficial SCCP levels in the Chinese East Seas
      by combining analysis with the data from the East China Sea (R(2) = 0.332, p <
      0.01). These findings indicated that the sources of SCCPs were mainly from river
      outflows via ocean current and partly from atmospheric depositions by East Asian
      monsoon in the sampling areas. 

PMID- 24024650
TI  - Quantitative analysis of gangliosides in bovine milk and colostrum-based dairy
      products by ultrahigh performance liquid chromatography-tandem mass spectrometry.
AB  - Milk gangliosides have gained considerable attention because they participate in
      diverse biological processes, including neural development, pathogen binding, and
      activation of the immune system. Herein, we present a quantitative measurement of
      the gangliosides present in bovine milk and other dairy products and byproducts.
      Ultrahigh performance liquid chromatography separation was used for high
      throughput analysis and achieved a short running time without sacrificing
      chromatographic resolution. Dynamic multiple reaction monitoring was conducted
      for 12 transitions for GM3 and 12 transitions for GD3. Transitions to sialic acid
      fragments (m/z 290.1) were chosen for the quantitation. There was a considerable
      amount of gangliosides in day 2 milk (GM3, 0.98 mg/L; GD3, 15.2 mg/L) which
      dramatically decreased at day 15 and day 90. GM3 and GD3 were also analyzed in
      pooled colostrum, colostrum cream, colostrum butter, and colostrum buttermilk.
      The separation and analytical approaches here proposed could be integrated into
      the dairy industry processing adding value to side-streams. 

PMID- 24024651
TI  - Hollow structured Li3VO4 wrapped with graphene nanosheets in situ prepared by a
      one-pot template-free method as an anode for lithium-ion batteries.
AB  - To explore good anode materials of high safety, high reversible capacity, good
      cycling, and excellent rate capability, a Li3VO4 microbox with wall thickness of
      40 nm was prepared by a one-pot and template-free in situ hydrothermal method. In
      addition, its composite with graphene nanosheets of about six layers of graphene
      was achieved. Both of them, especially the Li3VO4/graphene nanosheets composite,
      show superior electrochemical performance to the formerly reported vanadium-based
      anode materials. The composite shows a reversible capacity of 223 mAh g(-1) even
      at 20C (1C = 400 mAh g(-1)). After 500 cycles at 10C there is no evident capacity
      fading. 

PMID- 24024653
TI  - Substituent effects on noncovalent bonds: complexes of ionized benzene
      derivatives with hydrogen cyanide.
AB  - Here, we report the first experimental and computational study of the noncovalent
      binding energies and structures of ionized benzenes containing electron
      withdrawing substituents solvated by one to four HCN molecules. Measured by ion
      mobility mass spectrometric equilibrium studies, the bond dissociation enthalpies
      of the first HCN molecule to the fluorobenzene (C6H5F(*+)), 1,4-difluorobenzene
      (C6H4F2(*+)), and benzonitrile (C6H5CN(*+)) ions (11.2, 11.2, and 9.2 kcal/mol,
      respectively) are similar to those of HCN with the benzene (C6H6(*+)) and
      phenyacetylene (C6H5CCH(*+)) radical cations (9.2 and 10.5 kcal/mol,
      respectively). DFT calculations at the B3LYP/6-311++G(d,p) level show that HCN
      can form in-plane hydrogen bonds to ring hydrogens, or bind electrostatically to
      positively charged carbon centers in the ring. The electron-withdrawing
      substituents increase the bond energy by increasing the partial positive charge
      on the ring hydrogens that form CH(delta+)---NCH bonds, and by creating a pi
      hole, as evidenced by positive charge centers on the fluorinated ring carbons for
      electrostatically bonded isomers. In the complexes of benzonitrile(*+), similar
      to benzene(*+), hydrogen bonded planar isomers have the lowest energy. In the
      complexes of (fluorinated benzene)(*+), the lowest energy isomers are
      electrostatically bonded where HCN is perpendicular to the ring and its dipole
      points to a positively charged ring carbon. However, in all cases the planar
      hydrogen-bonded and vertical electrostatic isomers have similar binding energies
      within 1 kcal/mol, although HCN interacts with different sites of the ionized
      benzenes in these isomers, suggesting that the observed cluster populations are
      mixtures of the planar and vertical isomers. Further HCN molecules can bind
      directly to unoccupied ring CH hydrogens or bind to the first-shell HCN molecules
      to form linear HCN---HCN--- hydrogen bonded chains. The binding energies decrease
      stepwise to about 6-7 kcal/mol by 4 HCN molecules, approaching the macroscopic
      enthalpy of vaporization of liquid HCN (6.0 kcal/mol). 

PMID- 24024652
TI  - Bone microenvironment-targeted manipulations for the treatment of osteoblastic
      metastasis in castration-resistant prostate cancer.
AB  - INTRODUCTION: Most patients with advanced prostate cancer will develop incurable
      bone metastasis. Although prostate cancer is the quintessential androgen
      dependent neoplastic disease in males, the tumor will ultimately become
      refractory to androgen ablation treatment. Understanding the complex dialog
      between prostate cancer and the bone microenvironment has allowed the development
      of promising treatment strategies. AREAS COVERED: The present review summarizes
      the pathophysiology of prostate cancer bone metastasis and provides a concise
      update on bone microenvironment-targeted therapies for prostate cancer. The
      current and future prospects and challenges of these strategies are also
      discussed. EXPERT OPINION: A wide variety of signaling pathways, bone turnover
      homeostatic mechanisms and immunoregulatory networks are potential targets for
      the treatment of metastatic castration-resistant prostate cancer (mCRPC). Anti
      survival factor therapy can enhance the efficacy of existing treatment regimens
      for mCRPC by exploiting the interaction between the bone microenvironment and
      androgen signaling networks. In addition, many novel bone microenvironment
      targeted strategies have produced promising objective clinical responses. Further
      elucidation of the complex interactions between prostate cancer cells and the
      bone stroma will open up new avenues for treatment interventions that can produce
      sustained cancer suppression.

PMID- 24024654
TI  - Thymines in single-stranded oligonucleotides and G-quadruplex DNA are competitive
      with guanines for binding to an organoruthenium anticancer complex.
AB  - Organometallic ruthenium(II) complexes [(eta(6)-arene)Ru(en)Cl](+) (arene = e.g.,
      biphenyl (1), dihydrophenanthrene, tetrahydroanthracene) show promising
      anticancer activity both in vitro and in vivo and are cytotoxic to cisplatin
      resistant cancer cells, implying that these monofunctional complexes have a
      different mechanism of action from that of bifunctional cisplatin. We demonstrate
      here that complex 1 binds selectively to the guanine base in the 15-mer single
      stranded oligodeoxynucleotides (ODNs) 5'-CTCTCTX7G8Y9CTTCTC-3' [X = Y = T; X = C,
      Y = A; X = A, Y = T; X = T, Y = A] to form thermodynamically stable adducts, but
      thymine bases (T7/T11 or T6/T11) compete kinetically with guanine for binding to
      1. The T-bound monoruthenated species eventually convert to diruthenated products
      via a second step of binding at G or/and to G-bound monoruthenated species
      through dissociation of the diruthenated adducts. Complex 1 was further shown to
      bind preferentially to the middle T in a sequence rather than to a T near the
      terminus and favor coordination to a 5'-T compared to a 3'-T. Interestingly, the
      T bases in the human telomeric G-quadruplex sequence (5'-AGGGTTAGGGTTAGGGTTAGGG
      3') were found to be more competitive both kinetically and thermodynamically with
      G bases for binding to 1. These results suggest that thymine bases play a unique
      role in the pathways of ruthenation of DNA by organoruthenium anticancer
      complexes and illustrate that kinetic studies can provide new insight into the
      mechanism of action of metallodrugs in addition to study of the structures and
      functions of the thermodynamically stable end products. 

PMID- 24024655
TI  - A liquid crystal polymer-based neuromodulation system: an application on animal
      model of neuropathic pain.
AB  - OBJECTIVE: We developed a custom-made miniaturized neural stimulation system with
      a liquid crystal polymer (LCP)-based electrode array for animal experiments. In
      order to verify the feasibility of the system, motor cortex stimulation (MCS) was
      applied on the rat pain model induced by sciatic nerve injury. MATERIALS AND
      METHODS: LCP is mechanically stable and chemically inert and has a much lower
      water absorption rate than other biocompatible polymers such as polyimide or
      parylene. In the present study, a film-type LCP substrate is used to
      microfabricate the cortical stimulation electrode array. A miniaturized
      electrical neuromodulation system is implemented using an application-specific
      integrated chip for generation of electrical stimulation current. In vivo
      experiment was performed using a rat neuropathic pain model induced by sciatic
      nerve injury. The electrodes were attached to the contralateral primary motor
      cortex, which processes the hind limb movement. Mechanical allodynia was measured
      before, during, and after electrical stimulation to determine the effects on pain
      threshold. RESULTS: Electrical stimulation into the brain structure processing
      pain perception was effective in alleviating neuropathic pain. The pain threshold
      of the rats increased more than fivefold during the electrical stimulation.
      CONCLUSION: We developed a miniaturized electrical stimulation system with a
      novel flexible LCP electrode array for MCS in rats. This system is expected to be
      used in studying various neurological diseases and examining in vivo brain
      function.

PMID- 24024656
TI  - Design strategies for water-soluble small molecular chromogenic and fluorogenic
      probes.

PMID- 24024657
TI  - Secondary amenorrhea in severe Asherman's syndrome: step by step fertility
      retrieval by Bettocchi's hysteroscope: some considerations.
AB  - The aim of this report was to define the best diagnostic and therapeutic approach
      when secondary amenorrhea is related to undiagnosed Asherman syndrome. We present
      a single case of secondary amenorrhea with a previous diagnosis of alterated
      hypothalamic-hypophysary regulation, with a component of ovarian function in
      probable reduction, which was evaluated in our department and resulted affected
      by Asherman's syndrome IV stage. We describe step by step the diagnosis and
      treatment of a previously misdiagnosed case of severe Asherman's syndrome. An
      appropriate diagnosis and adequate treatment are mandatory to allow menses and
      fertility to be restored when severe Asherman's syndrome occurs.

PMID- 24024658
TI  - Analysis of the immunologic status of a newly diagnosed HIV positive population
      in China.
AB  - BACKGROUND: The immunologic status of a newly diagnosed HIV positive population
      in the era of antiretroviral therapy in China has not been extensively evaluated.
      We conducted a cross-sectional survey to evaluate the CD4 counts of newly
      diagnosed HIV-infected persons and determine the factors influencing these counts
      in China. METHODS: Two thousand eight hundred and sixty-six newly diagnosed HIV
      infected patients from 10 provinces in China were selected during 2009 to 2010.
      Serum samples were collected to measure CD4 counts by flow cytometry.
      Demographics and medical histories were recorded. Multivariate logistic
      regression models were used to analyze factors associated with low CD4 count
      (<100 cells/mm3) at HIV diagnosis. RESULTS: Among the 2866 patients, 2159
      (75.33%) were male. Mean age was 40 years (range: 18-86 years). The median CD4
      count at HIV diagnosis was 83 cells/mm3, 72.02% of the patients had a CD4 count
      that was <=200 cells/mm3, 53.98% had CD4 counts <100 cells/mm3. The difference in
      CD4 counts between males and females was not statistically significant (P=0.469).
      The median CD4 count differed significantly according to age (P=0.002), province
      (P<0.001), ethnicity (P<0.001) and HIV transmission route (P<0.001). In
      multivariate logistic analysis, factors associated with greater odds of low CD4
      count at HIV diagnosis included male sex, younger age, HIV transmission route
      classified as unknown transmission risk, having been diagnosed in provinces
      Guangxi, Henan, Heilongjiang, Jiangxi, Shanghai and Yunnan. CONCLUSIONS: At the
      time of HIV diagnosis, a large proportion of HIV-infected patients in China had
      an initial CD4 count that was consistent with relatively advanced disease. Low
      CD4 count was associated with male gender, younger age, route of HIV transmission
      and geographical areas. HIV testing policy that promotes routine testing for HIV
      infection is needed to facilitate earlier HIV diagnosis.

PMID- 24024659
TI  - Secondary cancers, comorbidities and mortality associated with nitrogen mustard
      therapy in patients with mycosis fungoides: a 30-year population-based cohort
      study.
AB  - BACKGROUND: Topical nitrogen mustard is a widely used therapy in patients with
      mycosis fungoides (MF). However, it remains controversial whether nitrogen
      mustard therapy is associated with increased risk of secondary cancers and
      chronic pulmonary diseases in patients with MF. OBJECTIVES: To assess the risk of
      secondary cancers, comorbidities, mortality and cause-specific mortality in
      patients with MF treated with nitrogen mustard compared with patients not
      receiving this treatment. METHODS: Linking the Danish nationwide registries in a
      30-year population-based cohort study, we compared 110 patients with MF from a
      regional Danish centre using nitrogen mustard treatment with 193 patients from
      Danish centres not using nitrogen mustard. The two cohorts were compared by Cox
      regression analysis. RESULTS: Overall, secondary cancers were not significantly
      increased [hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.46-1.56], and
      subanalyses showed no significantly increased risk of nonmelanoma skin cancers,
      malignant melanomas or cancers in the respiratory organs in the nitrogen mustard
      treated cohort. Furthermore, we found no significantly increased risk of any
      category of comorbidity, including chronic pulmonary diseases, in patients
      treated with nitrogen mustard (HR 0.93, 95% CI 0.48-1.81). Moreover, mortality
      and cause-specific mortality did not significantly differ between the two
      cohorts. CONCLUSIONS: This study does not support any previous suspicion of
      increased risk of secondary cancers and chronic pulmonary diseases among patients
      with MF treated with nitrogen mustard. Furthermore, mortality and cause-specific
      mortality were not influenced by nitrogen mustard treatment. Thus our findings
      indicate that topical nitrogen mustard is a safe therapy in patients with MF.

PMID- 24024660
TI  - A S52P mutation in the 'alpha-crystallin domain' of Mycobacterium leprae HSP18
      reduces its oligomeric size and chaperone function.
AB  - Mycobacterium leprae HSP18 is a small heat shock protein (sHSP). It is a major
      immunodominant antigen of M. leprae pathogen. Previously, we have reported the
      existence of two M. leprae HSP18 variants in various leprotic patients. One of
      the variants has serine at position 52, whereas the other one has proline at the
      same position. We have also reported that HSP18 having proline at position 52
      (HSP18P(52)) is a nonameric protein and exhibits chaperone function. However, the
      structural and functional characterization of wild-type HSP18 having serine at
      position 52 (HSP18S(52)) is yet to be explored. Furthermore, the implications of
      the S52P mutation on the structure and chaperone function of HSP18 are not well
      understood. Therefore, we cloned and purified these two HSP18 variants. We found
      that HSP18S(52) is also a molecular chaperone and an oligomeric protein.
      Intrinsic tryptophan fluorescence and far-UV CD measurements revealed that the
      S52P mutation altered the tertiary and secondary structure of HSP18. This point
      mutation also reduced the oligomeric assembly and decreased the surface
      hydrophobicity of HSP18, as revealed by HPLC and 4,4'-dianilino-1,1'-binaphthyl
      5,5'-disulfonic acid binding studies, respectively. Mutant protein was less
      stable against thermal and chemical denaturation and was more susceptible towards
      tryptic cleavage than wild-type HSP18. HSP18P(52) had lower chaperone function
      and was less effective in protecting thermal killing of Escherichia coli than
      HSP18S(52). Taken together, our data suggest that serine 52 is important for the
      larger oligomerization and chaperone function of HSP18. Because both variants
      differ in stability and function, they may have different roles in the survival
      of M. leprae in infected hosts.

PMID- 24024661
TI  - Effects of creatine supplementation on biomarkers of hepatic and renal function
      in young trained rats.
AB  - Creatine supplementation has been widely used by athletes and young physical
      exercise practioneers in order of increasing muscle mass and enhancing athletic
      performance, but their use/overuse may represent a health risk on hepatic and
      renal impaired function. In this study, we evaluated the effects of 40 days of
      oral creatine supplementation on hepatic and renal function biomarkers in a young
      animal model. Wistar rats (5 weeks old) were divided in five groups (n = 7):
      control (CONTR), oral creatine supplementation (CREAT), moderate exercise
      training (EXERC), moderate exercise training plus oral creatine supplementation
      (EXERC + CREAT) and pathological group (positive control for liver and kidney
      injury) by the administration of rifampicin (RIFAMPICIN). Exercise groups were
      submitted to 60 min/day of swimming exercise session with a 4% of body weight
      workload for six weeks. The EXERC + CREAT showed the higher body weight at the
      end of the training protocol. The CREAT and EXERC + CREAT group showed an
      increase in hepatic (Aspartate transaminase and gamma-glutamyl transpeptidase)
      and renal (urea and creatinine) biomarkers levels (p < 0.05). Our study showed
      that the oral creatine supplementation promoted hepatic and renal function
      challenge in young rats submitted to moderate exercise training.

PMID- 24024662
TI  - Kolaviron prevents ethylene glycol monoethyl ether-induced testicular apoptosis
      via down-regulation of stress proteins, Fas/Fas-L and caspases expressions in
      rats.
AB  - This study investigated the protective role of kolaviron, a natural antioxidant
      biflavonoid isolated from the seed of Garcinia kola, in ethylene glycol monoethyl
      ether (EGEE)-induced testicular dysfunction in male rats. Adult male Wistar rats
      were exposed to EGEE (200 mg/kg) separately or in combination with either
      kolaviron (100 or 200 mg/kg) or vitamin E (50 mg/kg) for 14 days. Immunoblot
      analysis revealed that EGEE exposure alone significantly increased stress
      inducible proteins levels. The increased protein expression of active caspases,
      Fas and Fas-L, was accompanied by nuclear factor kappa B downregulation and
      elevation of cytosolic cytochrome c level in EGEE-treated rats. In addition, the
      observation from immunofluorescence staining was consistent with the increased
      TUNEL-positive nuclei in the testes of EGEE-treated rats. Kolaviron and vitamin E
      significantly inhibited induction of stress proteins and germ cell apoptosis in
      EGEE-treated rats. Overall, kolaviron by virtue of its antioxidant and anti
      apoptotic properties prevented EGEE-induced reproductive toxicity in rats.

PMID- 24024663
TI  - Oxidative stress enzyme status and frequency of micronuclei in heroin addicts in
      Turkey.
AB  - Heroin is among the most widely used and dangerous addictive opiate. The World
      Health Organization (WHO) estimated that more than 15 million people are under
      the influence of opiate addiction. The aim of this study was to investigate
      copper zinc-superoxide dismutase (Cu,Zn-SOD), catalase (CAT) and selenium
      dependent glutathione peroxidase (Se-GPx) antioxidant enzyme activities,
      malondialdehyde (MDA) levels and the frequency of micronuclei (MN) in addicts
      using heroin, the most commonly abused opiate in Turkey. Addicts were defined as
      individuals diagnosed according to "Diagnostic and Statistical Manual of Mental
      Disorders, fourth edition (DSM-IV)" criteria by the "Alcohol and Substance Abuse
      Treatment and Education Centre-Ankara (AMATEM)". The control group had no
      addiction. In comparisons between the groups, a significant decrease in Cu,Zn-SOD
      activity and increases in MDA levels and MN frequency were observed in addicts.
      It can be concluded that opiates may cause oxidative stress and that antioxidant
      supplementation, in addition to pharmacological and psychiatric approaches, can
      reduce the toxicological effects of these opiates.

PMID- 24024664
TI  - Acquired multidrug resistance in human K562/ADM cells is associated with enhanced
      autophagy.
AB  - Autophagy, as a necessary process for survival in mammalian cells deprived of
      nutrients or growth factors, will be activated in many tumor cells while treated
      with chemotherapeutic drugs, but the role of autophagy in acquired multidrug
      resistance of human acute myelogenous leukemia to adriamycin-based chemotherapy
      remains to be clarified. Our aim was to address that question by surveying the
      autophagic activity in parental acute myelogenous leukemia cell line K562 and
      resistant sub cell line, K562/ADM, which were obtained by treating adriamycin
      with increasing concentrations. K562/ADM and K562 cells were exposed to PBS
      culture medium for 3 hours, then the stress-induced autophagy was measured. Real
      time quantitative RT-PCR revealed the expression of LC3 mRNA was higher in
      K562/ADM than in K562 cells. LC3-II, as an autophagosomal marker, was more
      abundant in K562/ADM than in K562 cells measured by Western blotting. To
      determine the effect of 3-MA, a known specific inhibitor of autophagy, on
      overcoming acquired multidrug resistance induced by adriamycin, the MTT assay and
      flow cytometry were performed. We also found that 3-MA can enhance the growth
      inhibition and apoptotic effect of adriamycin in acquired resistant cells
      (K562/ADM). Collectively, our results provide evidence that the upregulation of
      autophagy plays a major role in multidrug resistance of K562/ADM cells induced by
      adriamycin.

PMID- 24024665
TI  - Oxidative stress and lung injury induced by short-term exposure to wood smoke in
      guinea pigs.
AB  - Oxidative stress and lung injury induced by short-term exposure to wood smoke
      were evaluated in guinea pigs through cell profile, bronchoalveolar lavage (BAL),
      conventional histology and immunohistochemistry (4-hydroxynonenal, 3
      nitrotyrosine, Mn-superoxide dismutase, heme oxygenase-1); malondialdehyde and 4
      hydroxynonenal concentration, Mn-superoxide dismutase, glutathione reductase,
      glutathione peroxidase, and catalase activities in plasma, lung and BAL. Total
      cells increased in BAL, and the percentage of macrophages, neutrophils and
      lymphocytes augmented (72-96 h). Histopathological examination of lung tissues
      showed mild thickening of membranous bronchiole walls, infiltration of foamy
      macrophages and polymorphonuclear leukocytes in bronchial, bronchiolar and
      intraalveolar spaces. Goblet cell hyperplasia was also observed in bronchial and
      bronchiolar epithelia. Plasma malondialdehyde concentration was increased at all
      times, while 4-hydroxynonenal was increased only in plasma and BAL after 24 h.
      Plasma glutathione reductase activity increased at 24 and 72 h, BAL glutathione
      peroxidase activity decreased at 72 and 96 h, whereas catalase activity increased
      in plasma at 72 h, and decreased in BAL at 24 h. Immunostaining intensity to 4
      hydroxynonenal, 3-nitrotyrosine, Mn-superoxide dismutase and heme oxygenase-1 was
      enhanced mainly in macrophages, bronchial/bronchiolar epithelial cells and type
      II pneumocytes after 72-96 h of wood smoke exposure. Overall, short-term exposure
      to wood smoke induces alterations in oxidative/antioxidant state in lung and
      airway injury, similar to those observed in humans with domestic exposure.

PMID- 24024667
TI  - Luteolin, a bioflavonoid inhibits Azoxymethane-induced colorectal cancer through
      activation of Nrf2 signaling.
AB  - Colorectal cancer (CRC) is now perceived as a multistep process characterized by
      the accumulation of genetic alterations in oncogenes and tumor suppressor genes.
      Plant-derived compounds are receiving considerable attention for their potential
      role in reducing cancer risk. Luteolin, a bioflavonoid present in many fruits and
      vegetables, possesses antioxidant, anti-inflammatory and antiproliferative
      properties. This study was designed to investigate the possible role of luteolin
      administration on Phase 1 and 2 enzymes and NF-E2-related factor 2 (Nrf2)/keap1
      pathway. Male Balb/C mice were divided into four groups: normal control,
      Azoxymethane (AOM)-induced, AOM-induced and luteolin treated, normal control
      treated with luteolin. CRC was induced by administration of AOM (15 mg/kg body
      weight) intraperitoneally (i.p.) once a week for three weeks. Luteolin
      administration (1.2 mg/kg body weight/day) significantly alleviated Phase1
      enzymes in colon and liver, it increased the levels of phase 2 enzymes. Luteolin
      modulates the expressions of GST-alpha, u and also the expression of Nrf2.
      Collectively, results of our hypothesis show that luteolin is a novel candidate
      for treating CRC.

PMID- 24024668
TI  - Effect of sodium fluoride on neuroimmunological parameters, oxidative stress and
      antioxidative defenses.
AB  - AIMS: This study was designed to evaluate the effect of sodium fluoride (NaF) in
      inducing neuroimmunological, oxidative and antioxidative damage. METHODS: Twenty
      four male Wistar rats broadly grouped into four groups containing six rats in
      each were fed with drinking water containing 20 ppm, 60 ppm, 100 ppm and 0.8 ppm
      (control) NaF. After 90 days, rats were sacrificed to assess the level of
      fluoride content and various neurotransmitters in brain. The levels of CD4,
      natural killer (NK) cells and IgG1 were assessed in blood and spleen. In
      addition, lipid peroxidation coupled with the levels of various antioxidative
      enzymes was also recorded. RESULTS: Increase in the NaF concentration resulted in
      increased fluoride deposition in brain tissue. This increased fluoride content
      led to increased levels of certain neurotransmitters such as epinephrine,
      histamine, serotonin and glutamate and decreased levels of norepinephrine,
      acetylcholine and dopamine in a dose-dependent manner. NaF exposure led to the
      decrease in the levels of CD4, NK cells and IgG1 coupled with marked increase in
      lipid peroxidation and impairment of the antioxidative defense system.
      CONCLUSION: The result of the study emphasizes the toxic role of high NaF doses
      on the neurological and immunological functions.

PMID- 24024666
TI  - Proteomic identification of carbonylated proteins in the kidney of
      trichloroethene-exposed MRL+/+ mice.
AB  - Trichloroethene (TCE), a common environmental and occupational pollutant, is
      associated with multiorgan toxicity. Kidney is one of major target organs
      affected as a result of TCE exposure. Our previous studies have shown that
      exposure to TCE causes increased protein oxidation (protein carbonylation) in the
      kidneys of autoimmune-prone MRL+/+ mice, and suggested a potential role of
      protein oxidation in TCE-mediated nephrotoxicity. To assess the impact of chronic
      TCE exposure on protein oxidation, particularly to identify the carbonylated
      proteins in kidneys, female MRL+/+ mice were treated with TCE at the dose of 2
      mg/ml via drinking water for 36 weeks and kidney protein extracts were analyzed
      for protein carbonyls and carbonylated proteins identified using proteomic
      approaches (2D gel, Western blot, MALDI TOF/TOF MS/MS, etc.). TCE treatment led
      to significantly increased protein carbonyls in the kidney protein extracts (20
      000 g pellet fraction). Interestingly, among 18 identified carbonylated proteins,
      10 were found only in the kidneys of TCE-treated mice, whereas other 8 were
      present in the kidneys of both control and TCE-treated mice. The identified
      carbonylated proteins represent skeletal proteins, chaperones, stress proteins,
      enzymes, plasma protein and proteins involved in signaling pathways. The findings
      provide a map for further exploring the role of carbonylated proteins in TCE
      mediated nephrotoxicity.

PMID- 24024669
TI  - Ameliorating effect of S-2(omega-aminoalkylamino) alkylaryl sulfide (DRDE-07) on
      sulfur mustard analogue, 2-chloroethyl ethyl sulfide-induced oxidative stress and
      inflammation.
AB  - Sulfur mustard (SM; 2,2'-dichloro diethyl sulfide), an alkylating chemical
      warfare agent, poses a major threat in both military conflict and chemical
      terrorism situations. 2-chloroethyl ethyl sulfide (CEES) is a monofunctional
      analogue of SM, frequently used in laboratory settings, therefore increasing
      chances of its exposure. S-2(omega-aminoalkylamino) alkylaryl sulfide (DRDE-07)
      is an analogue of amifostine reported to have protective effects against SM but
      its effect on CEES is largely unexplored. Therefore, this study was planned to
      explore the effects of DRDE-07 against CEES-induced toxicity. 0.75 LD50 (1068
      mg/kg) of CEES was exposed percutaneously in the presence or absence of DRDE-07
      (249 mg/kg p.o.) which is given prophylactically (before 30 minute) to male mice.
      Animals were sacrificed on 24 h, 7th day and 14th day of CEES exposure, and
      tissues were collected to study oxidative stress and inflammatory markers. CEES
      exposure depleted intracellular GSH level and activities of GSH-linked enzymes
      (GR, GPx and GST) which play a major role in GSH metabolism. CEES exposure
      augmented lipid peroxidation indicating severe oxidative stress. It also
      initiated inflammation causing an increase in proinflammatory (IL1-alpha, IL1
      beta, IL-6, TNF-alpha and IFN-Upsilon) and corresponding decrease in anti
      inflammatory cytokines (IL-4 and IL-10). This was also accompanied by neutrophils
      infiltration indicated by higher than normal myeloperoxidase (MPO) levels. DRDE
      07 efficiently reduced the oxidative stress and also facilitated to resolve
      inflammatory alterations. This study thus evaluated the beneficial role of DRDE
      07 in ameliorating the deleterious effects of CEES and can be potentially used
      against SM/CEES poisoning.

PMID- 24024670
TI  - The effects of atorvastatin on oxidative stress in L-NAME-treated rats.
AB  - OBJECTIVES: Current evidence suggests that the beneficial vascular effects of
      statins are not limited to the statins' lipid-lowering properties; these drugs
      can also improve vascular endothelial cell function. Nomega-nitro-l-arginine
      methyl ester (L-NAME) is a potent synthetic nitric oxide inhibitor, and long-term
      oral L-NAME treatment is used to induce vascular lesions in experimental animal
      models. METHODS: We determined the effects of statins on protein carbonyl (PCO),
      lipid hydroperoxides (LHP), oxidized low-density lipoproteins (ox-LDL) and
      antioxidants such as paraoxonase 1 (PON1) and total thiols (T-SH) in long-term L
      NAME-treated rats. Adult male Wistar rats were divided into three groups, namely,
      control, L-NAME-treated (1 mg/mL in drinking water for three weeks), and
      atorvastatin plus L-NAME-treated (4 mg/kg/day atorvastatin for 1 week during the
      third week of L-NAME treatment) groups. RESULTS: In the L-NAME group, the ox-LDL,
      LHP and PCO were higher and the PON1 and T-SH were lower than the concentrations
      observed for the controls. When compared with the L-NAME group, the L-NAME plus
      atorvastatin group had significantly lower ox-LDL and LHP and higher PON1
      activities. Additionally, the elevated total cholesterol (TC) and low-density
      lipoprotein-C (LDL-C) in the L-NAME group were decreased by atorvastatin
      administration. TC and LDL-C were positively correlated with ox-LDL and LHP and
      negatively correlated with PON1 in all groups. High-density lipoprotein-C (HDL-C)
      was negatively correlated with ox-LDL. CONCLUSION: PON1 prevents LDL oxidation
      and inactivates LDL-derived oxidized phospholipids; its activity showed a
      pronounced decrease in the L-NAME treatment group and was increased in the
      atorvastatin group. Based on our findings, we concluded that the atorvastatin had
      HDL-related antioxidant activity as well as lipid-lowering properties.

PMID- 24024672
TI  - Introduction to the special issue on "ESDMC-2013: Electronic Structure and
      Dynamics of Molecules and Cluster".

PMID- 24024671
TI  - Risk factors predicting the need for additional surgery in consecutive esotropia.
AB  - PURPOSE: To evaluate the risk factors predicting surgical treatment in
      consecutive esotropia occurring after surgery for intermittent exotropia.
      METHODS: The clinical records of 52 patients with consecutive esotropia who
      underwent exotropia surgery were retrospectively reviewed. All patients
      demonstrated consecutive esotropia with diplopia or suppression for more than 1
      month after surgery for exotropia. Patients were divided into two groups (the
      surgical group and nonsurgical group) depending on whether surgery was required
      for consecutive esotropia. Surgery for esotropia was performed only in patients
      with more than 10 prism diopters (PD) esodeviation that persisted for a minimum
      of 6 months, those who had suppression in 1 eye or diplopia, and those who could
      not achieve fine stereopsis. The nonsurgical treatment up to 6 months
      postoperatively was part-time patching and prism therapy in both groups. Patient
      characteristics were evaluated in the two groups. RESULTS: The surgical group was
      composed of 17 patients and the nonsurgical group was composed of 35 patients.
      Age, gender, refractive error, best-corrected visual acuity, and postoperative
      overcorrection at 1 day were not significantly different in the two groups (P >
      .05). However, the distance strabismic angle at 1 month postoperatively was 2.5
      +/- 3.8 PD esodeviation (range: 14 PD esotropia to 4 PD exotropia) in the
      nonsurgical group and 5.4 +/- 5.1 PD esodeviation (range: 20 PD esotropia to
      orthotropia) in the surgical group; these values were statistically significant
      (P < .05). CONCLUSIONS: The clinically significant risk factor affecting the
      surgical decision for consecutive esotropia was a large esotropic angle at 1
      month postoperatively in this study.

PMID- 24024673
TI  - Evaluation of magnetic resonance imaging issues for a wirelessly powered lead
      used for epidural, spinal cord stimulation.
AB  - OBJECTIVE: The objective of this investigation was to evaluate magnetic resonance
      imaging (MRI) issues (magnetic field interactions, MRI-related heating, and
      artifacts) for a wirelessly powered lead used for spinal cord stimulation (SCS).
      MATERIALS AND METHODS: A newly developed, wirelessly powered lead (Freedom-4,
      Stimwave Technologies Inc., Scottsdale, AZ, USA) underwent evaluation for
      magnetic field interactions (translational attraction and torque) at 3 Tesla, MRI
      related heating at 1.5 Tesla/64 MHz and 3 Tesla/128 MHz, and artifacts at 3 Tesla
      using standardized techniques. MRI-related heating tests were conducted by
      placing the lead in a gelled-saline-filled phantom and performing MRI procedures
      using relatively high levels of radiofrequency energy. Artifacts were
      characterized using T1-weighted, spin echo (SE), and gradient echo (GRE) pulse
      sequences. RESULTS: The lead exhibited minor magnetic field interactions (2
      degree deflection angle and no torque). Heating was not substantial under 1.5
      Tesla/64 MHz (highest temperature change, 2.3 degrees C) and 3 Tesla/128 MHz
      (highest temperature change, 2.2 degrees C) MRI conditions. Artifacts were
      moderate in size relative to the size and shape of the lead. CONCLUSIONS: These
      findings demonstrated that it is acceptable for a patient with this wirelessly
      powered lead used for SCS to undergo MRI under the conditions utilized in this
      investigation and according to other necessary guidelines. Artifacts seen on
      magnetic resonance images may pose possible problems if the area of interest is
      in the same area or close to this lead.

PMID- 24024674
TI  - Promoting formation of noncrystalline Li2O2 in the Li-O2 battery with RuO2
      nanoparticles.
AB  - Low electrical efficiency for the lithium-oxygen (Li-O2) electrochemical reaction
      is one of the most significant challenges in current nonaqueous Li-O2 batteries.
      Here we present ruthenium oxide nanoparticles (RuO2 NPs) dispersed on multiwalled
      carbon nanotubes (CNTs) as a cathode, which dramatically increase the electrical
      efficiency up to 73%. We demonstrate that the RuO2 NPs contribute to the
      formation of poorly crystalline lithium peroxide (Li2O2) that is coated over the
      CNT with large contact area during oxygen reduction reaction (ORR). This unique
      Li2O2 structure can be smoothly decomposed at low potential upon oxygen evolution
      reaction (OER) by avoiding the energy loss associated with the decomposition of
      the more typical Li2O2 structure with a large size, small CNT contact area, and
      insulating crystals. 

PMID- 24024675
TI  - Discontinued drugs for pulmonary, allergy, gastrointestinal, arthritis (2012).
AB  - INTRODUCTION: Various compounds are developed to interfere with pathogenic
      pathways involved in inflammation processes. Some of them are able to enter the
      clinical development for different diseases with a common pathogenic denominator
      such as, for example, rheumatoid arthritis and chronic obstructive pulmonary
      disease (COPD), based on the preclinical evidence, but not all these molecules
      prove to be efficacious while tested in different phases of clinical development.
      AREAS COVERED: This review discusses about the drugs that were discontinued from
      further development for pulmonary, allergy, gastrointestinal and arthritis
      diseases EXPERT OPINION: Most of the drugs discontinued during 2012 were
      compounds with anti-inflammatory activity which were mostly designed to treat
      arthritis/rheumatoid arthritis. Some of these molecules were also intended for
      COPD. Many of them failed the late phases of the clinical development.

PMID- 24024676
TI  - Capillary electrophoresis/mass spectrometry of APTS-labeled glycans for the
      identification of unknown glycan species in capillary electrophoresis/laser
      induced fluorescence systems.
AB  - The examination of protein glycosylation is of high importance, especially in the
      (bio)pharmaceutical sector. The analysis of protein glycosylation is conducted
      routinely in high performance by capillary electrophoresis with laser-induced
      fluorescence (CE/LIF) using 8-aminopyrene-1,3,6-trisulfonic acid (APTS)-labeled
      glycans. In this work we present an optimized capillary electrophoresis/time-of
      flight mass spectrometry (CE/TOF-MS) methodology for these labeled glycans, which
      combines the high separation performance of CE with the high resolution,
      accuracy, and speed of TOF-MS for eased glycan identification. The system based
      on an acidic background electrolyte (BGE) provides a migration direction analogue
      to routine CE/LIF systems. Different BGE compositions, capillary dimensions,
      coatings, and instrumental parameters were tested to optimize the system with
      respect to separation efficiency and robustness. Subsequently, the CE/MS method
      optimized for acidic conditions was compared to an alkaline CE/MS method.
      Further, the mobilities of six APTS-labeled complex-type N-glycans were compared
      for both CE/MS methods and two standard CE/LIF approaches. For the acidic and
      alkaline BGE systems, the mobilities of sialylated glycans were shifted relative
      to nonsialylated glycans in comparison to common CE/LIF systems. However, in this
      study a straightforward unequivocal peak assignment was achieved for all unknown
      glycans in a medium complex glycan mixture from a fusion protein. 

PMID- 24024677
TI  - Photocatalytic process of simultaneous desulfurization and denitrification of
      flue gas by TiO2-polyacrylonitrile nanofibers.
AB  - TiO2 nanoparticles were successfully fabricated on electrospun polyacrylonitrile
      (PAN) nanofibers via the coupling of electrospinning and hydrothermal pathway. A
      straightforward photocatalysis oxidation process has been developed for
      simultaneous desulfurization and denitrification of flue gas using the TiO2-PAN
      photocatalyst. Also, the influences of some important operating parameters, such
      as titanium loading content of catalyst, flue gas humidity, flue gas flow, and
      inlet flue gas temperature on removal efficiencies of SO2 and NO were
      investigated. The results demonstrated that removal efficiencies of 99.3% for SO2
      and 71.2% for NO were attained under the following optimal experiment conditions:
      titanium loading content, 6.78 At %; gas flow rate, 200 mL/min; flue gas
      humidity, 5%; inlet flue gas temperature, 40  degrees C. Furthermore, the
      presumed reaction mechanism of SO2 and NO removal using TiO2-PAN photocatalyst
      under UV light was proposed. 

PMID- 24024678
TI  - The effectiveness and safety of short-contact dithranol therapy in paediatric
      psoriasis: a prospective comparison of regular day care and day care with
      telemedicine.
AB  - BACKGROUND: Evidence on the effectiveness and safety of short-contact dithranol
      therapy in paediatric psoriasis is sparse and based only on retrospective data.
      The best results are achieved in a time-consuming day-care setting. OBJECTIVES:
      To study prospectively the effectiveness and safety of short-contact dithranol
      therapy in paediatric psoriasis. In addition, the effectiveness, safety, duration
      of treatment and number of visits between regular day care and day care with
      telemedicine were compared. METHODS: Data were collected from the prospective
      observational Child-CAPTURE registry of children with psoriasis. Effectiveness
      was measured as the mean percentage improvement in Psoriasis Area and Severity
      Index (PASI). Safety was assessed by recording adverse events. The number of
      visits and duration of treatment were reported. RESULTS: For all patients a mean
      percentage reduction in PASI score of -69.3% was found, with no significant
      differences between regular day care and day care with telemedicine. The only
      adverse event reported was irritation of the skin. Neither the frequency of
      irritation during treatment nor the mean duration of treatment significantly
      differed between the two groups. Patients with telemedicine had significantly
      fewer visits. CONCLUSIONS: This first prospective observational study
      demonstrates that short-contact dithranol therapy in paediatric psoriasis is
      effective and safe. Regular day care and day care with telemedicine are equally
      effective. Telemedicine can be of additional value as it is less time consuming.
      We hope it will therefore make dithranol treatment appropriate for a larger
      number of children with psoriasis.

PMID- 24024685
TI  - Novel PTRF mutation in a child with mild myopathy and very mild congenital
      lipodystrophy.
AB  - BACKGROUND: Mutations in the PTRF gene, coding for cavin-1, cause congenital
      generalized lipodystrophy type 4 (CGL4) associated with myopathy. In CGL4,
      symptoms are variable comprising, in addition to myopathy, smooth and skeletal
      muscle hypertrophy, cardiac arrhythmias, and skeletal abnormalities. Secondary
      features are atlantoaxial instability, acanthosis nigricans, hepatomegaly,
      umbilical prominence and metabolic abnormalities related to insulin resistance,
      such as diabetes mellitus, hyperlipidemia and hepatic steatosis. CASE
      PRESENTATION: We describe a 3 year-old child of Moroccan origin with mild muscle
      phenotype, mainly characterized by mounding, muscle pain, hyperCKemia and mild
      caveolin 3 reduction on muscle biopsy. No CAV3 gene mutation was detected;
      instead we found a novel mutation, a homozygous single base pair deletion, in the
      PTRF gene. Only after detection of this mutation a mild generalized loss of
      subcutaneous fat, at first underestimated, was noticed and the diagnosis of
      lipodystrophy inferred. CONCLUSIONS: The PTRF gene should be investigated in
      patients with hyperCKemia, mild myopathy associated with spontaneous or
      percussion-induced muscle contractions like rippling or mounding, and no CAV3
      mutation. The analysis should be performed even if cardiac or metabolic
      alterations are absent, particularly in young patients in whom lipodystrophy may
      be difficult to ascertain.

PMID- 24024686
TI  - The potential application of rice bran wax oleogel to replace solid fat and
      enhance unsaturated fat content in ice cream.
AB  - The development of structure in ice cream, characterized by its smooth texture
      and resistance to collapse during melting, depends, in part, on the presence of
      solid fat during the whipping and freezing steps. The objective of this study was
      to investigate the potential application of 10% rice bran wax (RBW) oleogel,
      comprised 90% high-oleic sunflower oil and 10% RBW, to replace solid fat in ice
      cream. A commercial blend of 80% saturated mono- and diglycerides and 20%
      polysorbate 80 was used as the emulsifier. Standard ice cream measurements, cryo
      scanning electron microscopy (cryo-SEM), differential scanning calorimetry (DSC),
      and transmission electron microscopy (TEM) were used to evaluate the formation of
      structure in ice cream. RBW oleogel produced higher levels of overrun when
      compared to a liquid oil ice cream sample, creating a lighter sample with good
      texture and appearance. However, those results were not associated with higher
      meltdown resistance. Microscopy revealed larger aggregation of RBW oleogel fat
      droplets at the air cell interface and distortion of the shape of air cells and
      fat droplets. Although the RBW oleogel did not develop sufficient structure in
      ice cream to maintain shape during meltdown when a mono- and diglycerides and
      polysorbate 80 blend was used as the emulsifier, micro- and ultrastructure
      investigations suggested that RBW oleogel did induce formation of a fat globule
      network in ice cream, suggesting that further optimization could lead to an
      alternative to saturated fat sources for ice cream applications. 

PMID- 24024687
TI  - Stabilization of fish oil-in-water emulsions with oleosin extracted from canola
      meal.
AB  - International dietary guidelines advocate replacement of saturated and trans fat
      in food with unsaturated oils. Also, there is growing interest in incorporating
      highly unsaturated omega-3 oils in to food products due to beneficial health
      effects. A major obstacle to incorporating highly unsaturated oils in to food
      products is the extreme susceptibility to oxidative deterioration. Oil bodies
      were prepared from tuna oil, oleosin, and phospholipid mimicking natural oil
      bodies within oilseed. Oleosin was extracted from canola (Brassica napus) meal by
      solubilization in aqueous sodium hydroxide (pH 12) and subsequent precipitation
      at its isoelectric point of pH 6.5. The tuna oil artificial oil bodies (AOBs)
      readily dispersed in water to produce oil-in-water (o/w) emulsions, which did not
      coalesce on storage and were amenable to pasteurization using standard
      conditions. Accelerated oxidation studies showed that these AOB emulsions were
      substantially more resistant to lipid oxidation than o/w emulsions prepared from
      tuna oil using Tween40, sodium caseinate, and commercial canola protein isolate,
      respectively. There is potential to use commercial canola meal, which is cheap
      and abundant, as a natural source of oleosin for the preparation of physically
      and oxidatively stable food emulsions containing highly unsaturated oils. 

PMID- 24024688
TI  - Identification of bioactive candidate compounds responsible for oxidative
      challenge from hydro-ethanolic extract of Moringa oleifera leaves.
AB  - Free radicals trigger chain reaction and inflict damage to the cells and its
      components, which in turn ultimately interrupts their biological activities. To
      prevent free radical damage, together with an endogenous antioxidant system, an
      exogenous supply of antioxidant components to the body in the form of functional
      food or nutritional diet helps undeniably. Research conducted by the Natl. Inst.
      of Health claimed that Moringa oleifera Lam possess the highest antioxidant
      content among various natural food sources based on an oxygen radical absorbent
      capacity assay. In this study, a 90% (ethanol:distilled water--90:10) gradient
      solvent was identified as one of the best gradient solvents for the effectual
      extraction of bioactive components from M. oleifera leaves. This finding was
      confirmed by various antioxidant assays, including radical scavenging activity
      (that is, 1, 1-diphenyl-2-picrylhydrazyl, H(2)O(2), and NO radical scavenging
      assay) and total antioxidant capacity (that is, ferric reducing antioxidant power
      and molybdenum assay). High-performance liquid chromatography (HPLC) fingerprints
      of the 90% gradient extract visually showed few specific peaks, which on further
      analysis, using HPLC-DAD-ESI-MS, were identified as flavonoids and their
      derivatives. Despite commonly reported flavonoids, that is, kaempferol and
      quercetin, we report here for the 1st time the presence of multiflorin-B and
      apigenin in M. oleifera leaves. These findings might help researchers to further
      scrutinize this high activity exhibiting gradient extract and its bio-active
      candidates for fruitful clinical/translational investigations.

PMID- 24024689
TI  - Utilization of barley or wheat bran to bioconvert glutamate to gamma-aminobutyric
      acid (GABA).
AB  - This study deals with the utilization of agro-industrial wastes created by barley
      and wheat bran in the production of a value-added product, gamma-aminobutyric
      acid (GABA). The simple and eco-friendly reaction requires no pretreatment or
      microbial fermentation steps but uses barley or wheat bran as an enzyme source,
      glutamate as a substrate, and pyridoxal 5'-phosphate (PLP) as a cofactor. The
      optimal reaction conditions were determined on the basis of the temperatures and
      times used for the decarboxylation reactions and the initial concentrations of
      barley or wheat bran, glutamate, and PLP. The optimal reactions produced 9.2 mM
      of GABA from 10 mM glutamate, yielding a 92% GABA conversion rate, when barley
      bran was used and 6.0 mM of GABA from 10 mM glutamate, yielding a 60% GABA
      conversion rate, when wheat bran was used. The results imply that barley bran is
      more efficient than wheat bran in the production of GABA. 

PMID- 24024691
TI  - Obesity and food science being part of the solution.

PMID- 24024692
TI  - Efficacy of plant-derived antimicrobials as antimicrobial wash treatments for
      reducing enterohemorrhagic Escherichia coli O157:H7 on apples.
AB  - This study investigated the efficacy of 3 GRAS-status, plant-derived
      antimicrobials (PDAs), trans-cinnamaldehyde (TC), carvacrol (CR), and beta
      resorcylic acid (BR) applied as an antimicrobial wash for killing Escherichia
      coli O157:H7 on apples. "Red delicious" apples inoculated with a 5 strain mixture
      of E. coli O157:H7 were subjected to washing in sterile deionized water
      containing 0% PDA (control), 0.15% TC, 0.35% TC, 0.15% CR, 0.30% CR, 0.5% BR, or
      1% BR for 1, 3, and 5 min at 23  degrees C in the presence and absence of 1%
      soil, and surviving pathogen populations on apples were enumerated at each
      specified time. All PDAs were more effective in reducing E. coli O157:H7 compared
      to the water wash treatment (P < 0.05) and reduced the pathogen by 4- to 5-log
      CFU/apple in 5 min. Chlorine (1%) was the most effective treatment reducing the
      pathogen on apples to undetectable levels in 1 min (P < 0.05). Moreover, the
      antimicrobial effect of CR and BR was not affected by the presence of soil,
      whereas the efficacy of TC and BR was decreased in the presence of soil. Further,
      no bacteria were detected in the wash solution containing CR and BR; however, E.
      coli O157:H7 was recovered in the control wash water and treatment solutions
      containing TC and chlorine, in the presence of 1% soil (P < 0.05). Results
      suggest that the aforementioned PDAs, especially CR and BR could be used
      effectively to kill E. coli O157:H7 on apples when used as a wash treatment.
      Studies on the sensory and quality characteristics of apples treated with PDAs
      are needed before recommending their usage. 

PMID- 24024693
TI  - Distinguishing Nonpareil marketing group almond cultivars through multivariate
      analyses.
AB  - More than 80% of the world's almonds are grown in California with several dozen
      almond cultivars available commercially. To facilitate promotion and sale, almond
      cultivars are categorized into marketing groups based on kernel shape and
      appearance. Several marketing groups are recognized, with the Nonpareil Marketing
      Group (NMG) demanding the highest prices. Placement of cultivars into the NMG is
      historical and no objective standards exist for deciding whether newly developed
      cultivars belong in the NMG. Principal component analyses (PCA) were used to
      identify nut and kernel characteristics best separating the 4 NMG cultivars
      (Nonpareil, Jeffries, Kapareil, and Milow) from a representative of the
      California Marketing Group (cultivar Carmel) and the Mission Marketing Group
      (cultivar Padre). In addition, discriminant analyses were used to determine
      cultivar misclassification rates between and within the marketing groups. All 19
      evaluated carpological characters differed significantly among the 6 cultivars
      and during 2 harvest seasons. A clear distinction of NMG cultivars from
      representatives of the California and Mission Marketing Groups was evident from a
      PCA involving the 6 cultivars. Further, NMG kernels were successfully
      discriminated from kernels representing the California and Mission Marketing
      Groups with overall kernel misclassification of only 2% using 16 of the 19
      evaluated characters. Pellicle luminosity was the most discriminating character,
      regardless of the character set used in analyses. Results provide an objective
      classification of NMG almond kernels, clearly distinguishing them from kernels of
      cultivars representing the California and Mission Marketing Groups. 

PMID- 24024695
TI  - Quantitative image quality evaluation of pelvic computed tomography-based imaging
      systems: a novel concept in radiotherapy.

PMID- 24024694
TI  - The effect of gamma irradiation as a phytosanitary treatment on physicochemical
      and sensory properties of bartlett pears.
AB  - A major concern in exporting agricultural commodities is the introduction or
      spread of exotic quarantine pests to the new area. To prevent spread of insect
      pests, various phytosanitary measures are used. Worldwide commercial use of
      irradiation as a phytosanitary treatment has increased greatly in recent years;
      however, trade has been limited to tropical fruits. Bartlett pear is a major
      summer variety of California pears with great potential and market for export. In
      this study, the effect of gamma irradiation at dose levels of 400, 600, and 800
      Gy on physicochemical properties and sensory attributes of early and late harvest
      Bartlett pears was investigated. Firmness and color changes indicate that
      irradiation delayed the ripening of pears by 1 d. For the early harvest pears,
      scarring, bruising, and off flavor were significantly increased at the highest
      irradiation dose (800 Gy). The appearance of early harvest 800 Gy irradiated
      pears was the only attribute that received significantly (P <= 0.05) lower scores
      than the control in consumer testing. For the late harvest pears, the 400 Gy
      fruit had lowest levels of scarring and bruising as rated by trained panelist but
      consumers did not score the control and 800 Gy fruit differently for any
      attribute. Titratable acidity, total soluble solids, and chroma were
      significantly (P <= 0.05) decreased and hue increased by irradiation for the
      early harvest pears. These results suggest that there was a difference in
      radiotolerance of early and late harvest pears, but in both cases, irradiation at
      400 to 600 Gy seemed to maintain best quality. 

PMID- 24024696
TI  - Docetaxel, oxaliplatin and capecitabine (TEX regimen) in patients with metastatic
      gastric or gastro-esophageal cancer: results of a multicenter phase I/II study.
AB  - Three drug taxane-based regimens have shown activity in patients with metastatic
      or locally advanced gastric or gastro-esophageal cancer (GC/GEC). Limited
      tolerability of these regimens warrants treatment modification, particularly in
      regard of the proven equivalence of oxaliplatin and cisplatin as well as
      capecitabine and 5FU. Thus, a regimen with docetaxel (T), oxaliplatin (E) and
      capecitabine (X) was established and evaluated. METHODS: Patients with metastatic
      or locally advanced GC/GEC, adequate organ function, ECOG PS 0-2 were enrolled.
      TEX regimen was administered as defined by the phase I trial with T 35 mg/m(2)
      and E 70 mg/m(2) on days (d) 1, 8 and X 800 mg/m(2) bid on d 1-14 every 22 days.
      Primary endpoint was progression free survival (PFS) rate after 6 months.
      RESULTS: Altogether 70 patients (15 phase I; 55 phase II) were eligible for
      analysis. Results of the phase II part were as follows: most common grade
      toxicities diarrhea (30%), nausea/vomiting and infections, PFS rate after 6
      months 56.3%, response rate 43%, median PFS 6.9 and overall survival 13 months,
      respectively. CONCLUSION: The TEX regimen show similar efficacy compared to other
      infusional 5FU-based taxane and platinum containing triplets, but the reduced
      tolerability, in particular grade 3 diarrhea, limits the feasibility.

PMID- 24024697
TI  - Regorafenib use as a possible cause of intestinal perforation.

PMID- 24024698
TI  - Homoleptic cerium(III) and cerium(IV) nitroxide complexes: significant
      stabilization of the 4+ oxidation state.
AB  - Electrochemical experiments performed on the complex Ce(IV)[2-((t)BuNO)py]4,
      where [2-((t)BuNO)py](-) = N-tert-butyl-N-2-pyridylnitroxide, indicate a 2.51 V
      stabilization of the 4+ oxidation state of Ce compared to [(n)Bu4N]2[Ce(NO3)6] in
      acetonitrile and a 2.95 V stabilization compared to the standard potential for
      the ion under aqueous conditions. Density functional theory calculations suggest
      that this preference for the higher oxidation state is a result of the
      tetrakis(nitroxide) ligand framework at the Ce cation, which allows for effective
      electron donation into, and partial covalent overlap with, vacant 4f orbitals
      with delta symmetry. The results speak to the behavior of CeO2 and related solid
      solutions in oxygen uptake and transport applications, in particular an inherent
      local character of bonding that stabilizes the 4+ oxidation state. The results
      indicate a cerium(IV) complex that has been stabilized to an unprecedented degree
      through tuning of its ligand-field environment. 

PMID- 24024699
TI  - The antidepressants fluoxetine and bupropion differentially affect proceptive
      behavior in the naturally cycling female rat.
AB  - INTRODUCTION: Fluoxetine, like other selective serotonin reuptake inhibitors,
      inhibits women's sexual desire and female rats' sexual behavior. Bupropion
      produces pro-sexual effects in women with and without depression, and yohimbine
      increases men's and male rats' sexual motivation, but their effects on female
      rats' proceptivity are unknown. AIM: To investigate the effects of fluoxetine,
      bupropion, and yohimbine on proceptivity and receptivity in the naturally cycling
      female rat. METHODS: We studied the effect of chronic (minimum 14 days)
      fluoxetine (1.25 mg/kg, subcutaneous) and bupropion (5 mg/kg, intraperitoneal)
      and acute yohimbine (1 mg/kg, intraperitoneal) on sexual behavior of female rats
      selected in natural proestrus during an ejaculatory series. We also analyzed the
      effects of these treatments on locomotor activity. MAIN OUTCOME MEASURES: The
      main outcome measures were frequencies of hops/darts and ear wiggling, lordosis
      quotient and intensity, and locomotor activity. RESULTS: Fluoxetine inhibited ear
      wiggling and hopping/darting, while bupropion stimulated hopping/darting. These
      treatments did not modify the lordosis quotient and its intensity. Yohimbine did
      not change any aspect of female sexual behavior. At the doses and treatments
      used, fluoxetine and bupropion did not alter locomotor activity or disturb the
      length of the estrous cycle; however, yohimbine inhibited locomotor activity.
      CONCLUSIONS: The motivational components of female sexual behavior are more
      sensitive than the receptive components to the inhibitory actions of fluoxetine.
      Bupropion selectively stimulated hopping/darting, while yohimbine lacked an
      action on female sexual behavior.

PMID- 24024700
TI  - Adjuvant treatment for elderly patients with early-stage lung cancer treated with
      limited resection.
AB  - OBJECTIVES: Limited resection is commonly used for treating older patients with
      early-stage non-small cell lung cancer (NSCLC) who cannot tolerate lobectomy.
      However, parenchymal-sparing procedures leave patients at increased risk of
      recurrence. The role of postoperative radiotherapy (PORT) and chemotherapy after
      limited resection is not established. METHODS: We identified 1,929 patients with
      stage I-II (<= 5 cm in size) NSCLC who underwent limited resection (wedge or
      segmentectomy) from the Surveillance, Epidemiology, and End Results (SEER)
      Medicare linked database. Using propensity score methods, we compared toxicity
      and survival of patients treated with limited resection alone, PORT, adjuvant
      chemotherapy, or PORT and chemotherapy. We conducted secondary analysis
      stratifying the sample by size (>2-5 cm), stage (IA vs. IB/IIA), and type of
      limited resection (wedge resection vs. segmentectomy). MEASUREMENTS AND MAIN
      RESULTS: Overall, 1,656 (85.8%), 159 (8.3%), 74 (3.8%), and 40 (2.1%) patients
      were treated with limited resection alone, PORT, adjuvant chemotherapy, or PORT
      and chemotherapy, respectively. Adjusted analysis using inverse probability
      weighting showed that PORT (hazard ratio [HR], 1.57; 95% confidence interval
      [CI], 1.45-1.69), adjuvant chemotherapy (HR, 1.48; 95% CI, 1.36-1.61), and PORT
      and chemotherapy (HR, 1.73; 95% CI, 1.61-1.86) were associated with worse
      survival compared with limited resection alone. Similar results were obtained in
      secondary analyses. Compared with limited resection alone, the adjusted odds
      ratios for toxicity were 1.97 (95% CI, 1.6-2.4), 3.15 (95% CI, 2.58-3.85), 2.59
      (95% CI, 2.0-3.4) for PORT, chemotherapy, and PORT and chemotherapy,
      respectively. CONCLUSIONS: PORT and adjuvant chemotherapy are not beneficial and
      appear to be associated with increased toxicity and worse survival after limited
      resection in elderly patients with early-stage NSCLC. Alternative strategies
      should be explored to improve local control.

PMID- 24024701
TI  - Colesevelam for Type 2 diabetes mellitus: an abridged Cochrane review.
AB  - AIM: Colesevelam, a second-generation bile acid sequestrant, may be beneficial in
      controlling both glycaemia and lipids simultaneously. Our goal was to evaluate
      the systemic effects of colesevelam on Type 2 diabetes mellitus. METHOD: The
      original Cochrane review was conducted using the methodology for the systematic
      review of interventions of the Cochrane Collaboration in RevMan 5.2. We
      comprehensively searched the literature in several databases up to January 2012.
      Two reviewing authors independently selected and extracted the data, and then
      evaluated the quality of the randomized controlled trials that met the inclusion
      criteria. RESULTS: Six randomized controlled trials were selected, which ranged
      from 8 to 26 weeks in duration. A total of 1450 participants were divided into
      two groups: those treated with colesevelam and no other anti-diabetic drug
      treatments/placebo, or with colesevelam added on to anti-diabetic drug
      treatments. The colesevelam added on to anti-diabetic agents demonstrated a
      statistically significant reduction in the fasting blood glucose (mean difference
      of -0.82 mmol/l, 95% CI -1.2 to -0.44), HbA1c (mean difference -0.5%, 95% CI -0.6
      to -0.4) and LDL cholesterol (mean difference -0.34 mmol/l, 95% CI -0.44 to 
      0.23). There were no reported data on weight. Non-severe hypoglycaemic episodes
      were infrequently observed. CONCLUSION: The limited number of studies concerning
      the treatment with colesevelam added to anti-diabetic agents showed significant
      effects on glycaemic control; however, more research on the reduction of
      cardiovascular risks is required. Furthermore, long-term data on the health
      related quality of life and all-cause mortality also need to be investigated.

PMID- 24024703
TI  - Surface reconstruction by a "grafting through" approach: polyacrylamide grafted
      onto chitosan film.
AB  - Grafted polymers and polymer brushes in particular have attracted significant
      attention in the last 2 decades as a way to alter and control interfacial
      properties. In the case of polymer brushes on solid substrates, a high grafting
      density of polymer chains results in stretching of the polymer coils normal to
      the substrate surface due to the effect of excluded volume. In this study,
      polyacrylamide is grafted to the surface of relatively soft thin films of
      chitosan. The "grafting through" approach is used by introducing double C?C bonds
      to amino groups of chitosan. The acquired kinetic data of grafting along with AFM
      and ellipsometry characterization suggest that the chitosan substrate undergoes
      surface reconstruction during the grafting of PAAm and simultaneously induces
      PAAm growth inside the soft substrate. As a result, much higher amounts of
      grafted polymer are achieved in comparison to traditional hard substrates like
      silicon or glass. Additionally, selective plasma etching of PAAm reveals filament
      like structures oriented normal to the surface. 

PMID- 24024704
TI  - Salmon patch conjunctiva associated with odontogenic infection.

PMID- 24024705
TI  - Randomised clinical trial: MRCP-first vs. ERCP-first approach in patients with
      suspected biliary obstruction due to bile duct stones.
AB  - BACKGROUND: The preferred initial investigation with either magnetic resonance
      (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) in patients with
      suspected biliary obstruction remains controversial in many clinical settings.
      AIM: To assess the effectiveness of an initial MRCP vs. ERCP in the work-up of
      patients at moderate likelihood of a suspected biliary obstruction. METHODS:
      Patients with an unconfirmed benign biliary obstruction, based on laboratory and
      ultrasound findings, were randomised to an ERCP-first or MRCP-first strategy,
      stratified by level of obstruction. The primary outcome was the occurrence of a
      disease or procedure-related bilio-pancreatic adverse events within the next 12
      months. Secondary outcomes were the number of subsequent bilio-pancreatic
      procedures, duration of hospitalisation, days away from activities of daily
      living (ADL), quality of life (SF-36) and mortality. RESULTS: We randomised 126
      patients to ERCP-first and 131 to MRCP-first (age 54 +/- 18 years, 62% female,
      39% post-cholecystectomy). In follow-up, 18/126 (14.3%) ERCP-first and 25/131
      (19.1%) MRCP-first patients experienced a procedure- or disease-related
      complication (P = 0.30) (disease-related in 13 and 18 patients, and procedure
      related in 5 and 7 patients respectively). A cause of biliary obstruction was
      found in 39.7% vs. 49.6% of patients (P = 0.11). Sixty-six (50%) patients in the
      MRCP-first group ended up avoiding an ERCP in follow-up. ERCP-first and MRCP
      first patients were away from usual activities for 3.4 +/- 7.7 days and 2.0 +/-
      4.8 days respectively (P < 0.001). CONCLUSION: A strategy of MRCP-first decreased
      the need for subsequent MRCPs, but not complications. Further study is required
      to define factors influencing the eventual use of MRCP vs. ERCP in appropriately
      selected patients (ClinicalTrial.gov: NCT01424657).

PMID- 24024702
TI  - Alzheimer's disease: pathophysiology and applications of magnetic nanoparticles
      as MRI theranostic agents.
AB  - Alzheimer's disease (AD) is the most common form of dementia. During the recent
      decade, nanotechnology has been widely considered, as a promising tool, for
      theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology
      and characteristics of AD with a focus on the amyloid cascade hypothesis. Then
      magnetic nanoparticles (MNPs) and recent works on their applications in AD,
      focusing on the superparamagnetic iron oxide nanoparticles (SPIONs), are
      reviewed. Furthermore, the amyloid-nanoparticle interaction is highlighted, with
      the scope to be highly considered by the scientists aiming for diagnostics and/or
      treatment of AD employing nanoparticles. Furthermore, recent findings on the
      "ignored" parameters (e.g., effect of protein "corona" at the surface of
      nanoparticles on amyloid-beta (Abeta) fibrillation process) are discussed. 

PMID- 24024706
TI  - The exception proves the rule? Dual targeting of nuclear-encoded proteins into
      endosymbiotic organelles.
AB  - Plant cells harbor two types of endosymbiotic organelle: mitochondria and
      chloroplasts. As a consequence of endosymbiotic gene transfer, the majority of
      their proteins are encoded in the nucleus and post-translationally 're'-imported
      into the respective target organelle. The corresponding transport signals are
      usually selective for a single organelle, but several proteins are transported
      into both the mitochondria and chloroplasts. To estimate the number of proteins
      with such dual targeting properties in Arabidopsis, we classified the proteins
      encoded by nuclear genes of endosymbiotic origin according to the respective
      targeting specificity of their N-terminal transport signals as predicted by the
      TargetP software package. Selected examples of the resulting protein classes were
      subsequently analyzed by transient transformation assays as well as by in
      organello protein transport experiments. It was found that most proteins with
      high prediction values for both organelles show dual targeting with both
      experimental approaches. Unexpectedly, however, dual targeting was even found
      among those proteins that are predicted to be localized solely in one of the two
      endosymbiotic organelles. In total, among the 16 candidate proteins analyzed, we
      identified 10 proteins with dual targeting properties. This unexpectedly high
      proportion suggests that such transport properties are much more abundant than
      anticipated. 

PMID- 24024707
TI  - Active RHOA favors retention of human hematopoietic stem/progenitor cells in
      their niche.
AB  - BACKGROUND: Hematopoietic stem/progenitor cells (HSPCs) maintain the
      hematopoietic system by balancing their self-renewal and differentiation events.
      Hematopoietic stem cells also migrate to various sites and interact with their
      specific microenvironment to maintain the integrity of the system. Rho GTPases
      have been found to control the migration of hematopoietic cells and other cell
      types. Although the role of RAC1, RAC2 and CDC42 has been studied, the role of
      RHOA in human hematopoietic stem cells is unclear. RESULTS: By utilizing
      constitutively active and dominant negative RHOA, we show that RHOA negatively
      regulates both in vitro and in vivo migration and dominant negative RHOA
      significantly increased the migration potential of human HSC/HPCs. Active RHOA
      expression favors the retention of hematopoietic stem/progenitor cells in the
      niche rather than migration and was found to lock the cells in the G0 cell cycle
      phase thereby affecting their long-term self-renewal potential. CONCLUSION: The
      current study demonstrates that down-regulation of RHOA might be used to
      facilitate the migration and homing of hematopoietic stem cells without affecting
      their long-term repopulating ability. This might be of interest especially for
      increasing the homing of ex vivo expanded HSPC.

PMID- 24024709
TI  - How should we spend the money?

PMID- 24024708
TI  - Bilateral deep brain stimulation of the ventral intermediate nucleus of the
      thalamus for posttraumatic midbrain tremor.

PMID- 24024714
TI  - Struggling trusts to receive extra funding before winter.

PMID- 24024715
TI  - Ambulatory care units opened to treat patients close to home.

PMID- 24024716
TI  - Emergency services becoming unsustainable warns committee.

PMID- 24024718
TI  - Board's eye view: blueprint for the future.

PMID- 24024723
TI  - Managing boxer's fracture: a literature review.
AB  - Boxer's fractures are commonly seen in emergency departments (EDs) but how these
      injuries are managed varies widely. This article reports on the results of a
      literature review of management strategies and the development of a boxer's
      fracture care pathway in a London ED. 

PMID- 24024724
TI  - Diagnosing Achilles tendon injuries in the emergency department.
AB  - Achilles tendon (AT) injury is an overuse injury often seen in professional and
      recreational athletes. It tends to affect men, particularly those in their
      thirties and forties, more than women, and is typically seen in people who are
      intermittently active. To ensure AT ruptures are identified and treated
      effectively, early intervention in emergency departments (EDs) is crucial. This
      article discusses how advanced nurse practitioners can use their comprehensive
      problem-solving, clinical decision-making and clinical judgement skills to manage
      patients who present with suspected AT injury. It also describes the anatomy of
      tendon rupture, the aetiology and mechanism of injuries, and the importance of
      assessment and diagnostic tools, therapeutic techniques and management
      strategies. Finally, it considers the psychological effect this injury can have
      on patients, while in the ED and after discharge. A case study is included as an
      example of ED management. 

PMID- 24024725
TI  - Gynaecological assessment and history taking.
AB  - Nurse practitioners (NPs) rarely undertake gynaecological histories or female
      genital examinations yet, by doing so, they can broaden their scope of practice.
      This article discusses what NPs should ask women about their gynaecological
      histories and how to undertake pelvic examinations, and reviews common
      gynaecological symptoms. Further articles will cover different aspects of the
      pelvic examination and potential differential diagnoses. 

PMID- 24024726
TI  - High flyer.

PMID- 24024728
TI  - Synthesis of dihydroxymethyl dihydroxypyrrolidines and steviamine analogues from
      C-2 formyl glycals.
AB  - Synthesis of dihydroxymethyl dihydroxypyrrolidines from C-2 formyl D-glycals has
      been described via a common dicarbonyl intermediate. The hence obtained
      pyrrolidines have been further utilized for the synthesis of some steviamine
      analogues. The newly synthesized molecules have been evaluated for glycosidase
      inhibition against 6 commercially available enzymes and found to be active in the
      micromolar range, where one of the steviamine analogues showed good and selective
      inhibition of beta-mannosidase (Helix pomatia).

PMID- 24024727
TI  - Effect of exercise training and dopamine agonists in patients with uremic
      restless legs syndrome: a six-month randomized, partially double-blind, placebo
      controlled comparative study.
AB  - BACKGROUND: Restless Legs Syndrome is very common in hemodialysis patients
      however there are no comparative studies assessing the effectiveness of a non
      pharmacological treatment to a classical treatment on parameters related to
      syndromes' severity and quality of life. METHODS: In this randomized, partially
      double blind, placebo controlled trial, thirty two hemodialysis patients with
      restless legs syndrome were randomly assigned into three groups: 1) the exercise
      training group (N = 16), 2) the dopamine agonists group (ropinirole 0.25 mg/d) (N
      = 8) and 3) the placebo group (N = 8). The intervention programs lasted 6 months.
      Restless Legs Syndrome severity was assessed using the international severity
      scale, physical performance by a battery of tests, muscle size and composition by
      computed tomography, body composition by Dual Energy X Ray Absorptiometry, while
      depression score, sleep quality, daily sleepiness and quality of life were
      assessed through questionnaires. RESULTS: Exercise training and dopamine agonists
      were effective in reducing syndrome's symptoms by 46% (P = 0.009) and 54% (P =
      0.001) respectively. Within group changes revealed that both approaches
      significantly improved quality of life (P < 0.05), however, only the dopamine
      agonists significantly improved sleep quality (P = 0.009). Within group changes
      showed a tendency for lean body mass improvements with dopamine agonists, this
      reached statistical significance only with the exercise training (P = 0.014),
      which also reduced fat infiltration in muscles (P = 0.044) and improved physical
      performance (P > 0.05) in various tests. Between group changes detect significant
      improvements with both exercise and dopamine agonists in depression score (P =
      0.003), while only the dopamine agonist treatment was able to significantly
      improve sleep quality, compared to exercise and placebo (P = 0.016). CONCLUSIONS:
      A 6-month exercise training regime was as effective as a 6-month low dosage
      dopamine agonist treatment in reducing restless legs syndrome symptoms and
      improving depression score in uremic patients. Further research is needed in
      order to show whether a combination treatment could be more beneficial for the
      amelioration of RLS. TRIAL REGISTRATION: NCT00942253.

PMID- 24024734
TI  - Attenuation of ultraviolet A-induced alterations in NIH3T3 dermal fibroblasts by
      melatonin.
AB  - BACKGROUND: Sun exposure is responsible for long-term clinical skin changes such
      as photoageing, photodamage and photocancers. Ultraviolet (UV)A wavelengths
      stimulate the production of reactive oxygen species (ROS) that may contribute to
      photoageing. To protect against oxidative stress, skin cells have developed
      several defence systems, including ROS and metal ion scavengers and a battery of
      detoxifying, haem-degrading and repair enzymes. Melatonin's antioxidant activity
      is the result of three different but complementary actions: (i) a direct action
      due to its ability to act as a free radical scavenger; (ii) an indirect action
      that is a consequence of melatonin's ability to reduce free radical generation
      (radical avoidance); and (iii) its ability to upregulate antioxidant enzymes.
      OBJECTIVES: In this study, we focused our attention on the prevention of
      photodamage, choosing melatonin as an antioxidant agent. METHODS: In the present
      study we analysed the effects of pretreatment of murine fibroblasts cells
      (NIH3T3) with melatonin (1 mmol L(-1) ) followed by UVA irradiation (15 J cm(-2)
      ). Thereafter, changes in components of the extracellular matrix and in some
      antioxidant enzymes (inducible and constitutive haem oxygenase) were evaluated.
      RESULTS: We observed that UVA radiation caused altered expression of
      extracellular matrix proteins and induced the expression of inducible haem
      oxygenase. This increase was not sufficient to protect the cells from damage.
      Instead, melatonin pretreatment led to increased expression of haem-degrading
      enzymes and suppression of UVA-induced photodamage. CONCLUSIONS: These results
      suggest that melatonin, as a modifier of the dermatoendocrine system, may have
      utility in reducing the effects of skin ageing.

PMID- 24024735
TI  - A mimetic tissue model for the quantification of drug distributions by MALDI
      imaging mass spectrometry.
AB  - The full potential of imaging mass spectrometry (IMS) as a tool in drug
      development will not be realized until reliable quantitative information can be
      integrated with the molecular distributions. Here we report a novel method for
      the quantification of drugs in tissue sections using matrix-assisted laser
      desorption/ionization (MALDI) IMS. This method uses a mimetic tissue model
      consisting of a set of tissue homogenates spiked with a range of different drug
      concentrations that have been frozen into a polymer support mold. The goal of
      this model is to mimic a dosed tissue in its effects on analyte extraction and
      ion suppression. Parallel preparation and analysis of sections from the tissue
      model and the dosed tissues allow for the quantification of a drug's
      distribution. Here we detail the steps involved in constructing the model and
      provide proof of concept data to highlight the potential of this approach.
      Several figures of merit are evaluated including linearity of response,
      variability, and section-to-section reproducibility. Finally, the tissue model is
      used to quantify two different drugs, lapatinib and nevirapine, in dosed tissues
      from nonclinical species and the results are compared with those generated by LC
      MS quantification. 

PMID- 24024737
TI  - alpha-ScVSe2O8, beta-ScVSe2O8, and ScVTe2O8: new quaternary mixed metal oxides
      composed of only second-order Jahn-Teller distortive cations.
AB  - Three new quaternary scandium vanadium selenium/tellurium oxides, alpha-ScVSe2O8,
      beta-ScVSe2O8, and ScVTe2O8 have been synthesized through hydrothermal and
      standard solid-state reactions. Although all three reported materials are
      stoichiometrically similar, they exhibit different crystal structures: alpha
      ScVSe2O8 has a three-dimensional framework structure consisting of ScO6, VO6, and
      SeO3 groups. beta-ScVSe2O8 reveals another three-dimensional framework composed
      of ScO7, VO5, and SeO3 polyhedra. ScVTe2O8 shows a layered structure with ScO6,
      VO4, and TeO4 polyhedra. Interestingly, the constituent cations, that is, Sc(3+),
      V(5+), Se(4+), and Te(4+) are all in a distorted coordination environment
      attributable to second-order Jahn-Teller (SOJT) effects. Complete
      characterizations including infrared spectroscopy, elemental analyses, thermal
      analyses, dipole moment calculation, and the magnitudes of out-of-center
      distortions for the compounds are reported. Transformation reactions suggest that
      alpha-ScVSe2O8 may change to beta-ScVSe2O8, and then to Sc2(SeO3)3.H2O under
      hydrothermal conditions. 

PMID- 24024736
TI  - Introducing carbon diffusion barriers for uniform, high-quality graphene growth
      from solid sources.
AB  - Carbon diffusion barriers are introduced as a general and simple method to
      prevent premature carbon dissolution and thereby to significantly improve
      graphene formation from the catalytic transformation of solid carbon sources. A
      thin Al2O3 barrier inserted into an amorphous-C/Ni bilayer stack is demonstrated
      to enable growth of uniform monolayer graphene at 600  degrees C with domain
      sizes exceeding 50 MUm, and an average Raman D/G ratio of <0.07. A detailed
      growth rationale is established via in situ measurements, relevant to solid-state
      growth of a wide range of layered materials, as well as layer-by-layer control in
      these systems. 

PMID- 24024738
TI  - Limited waterborne acute toxicity of native polycyclic aromatic compounds from
      coals of different types compared to their total hazard potential.
AB  - Coals contain native polycyclic aromatic compounds (PACs), which include
      polycyclic aromatic hydrocarbons (PAHs), and heterocyclic aromatic compounds (NSO
      PACs) in considerably varying amounts up to 2500 mg/kg. Whereas PAC
      bioavailability and toxicity from coals are generally considered to be low, few
      studies have considered potential variations arising from the composition of
      different coal types including native PAC content. In the present study, fine
      particles of different coal types exhibiting variable properties were
      systematically investigated regarding their PAC bioavailability. PAH content
      reached up to 79 mg/kg EPA-PAH and 865 mg/kg total PAH. Determination of the
      toxic potential of extracted PACs in bioassays showed inhibition of
      Caenorhabditis elegans reproduction (up to 94%) and increased mortality of Danio
      rerio embryos (up to 100%) after exposure to extracts from lignite, sub
      bituminous, and bituminous coals. Anthracite extracts showed no effects. Contact
      assays using whole coal samples revealed no toxicity to D. rerio embryos in any
      of the coal samples, suggesting low bioavailability of PACs. In contrast, C.
      elegans reproduction was inhibited by direct coal contact; however, the observed
      toxicity probably resulted from other coal effects. The results suggest that
      despite the high toxic potential of PACs present, their bioavailability from
      different coal types is very limited and independent of coal properties and
      native PAH content. 

PMID- 24024740
TI  - Family sense of coherence and family adaptation among childbearing couples.
AB  - PURPOSE: A family sense of coherence is important to successful family adaptation
      during parental transition. The purpose of this study was to examine the
      relationships between family sense of coherence, stress, family and marital
      functioning, and depressive symptoms among Chinese childbearing couples. DESIGN:
      A cross-sectional design was used. Two hundred and twenty-four Chinese
      childbearing couples were recruited at the antenatal clinic between January and
      May 2011. METHODS: Data were collected using the Family Sense of Competence
      Scale, Social Readjustment Rating Scale, Medical Outcome Study Family and Marital
      Functioning Measures, and General Health Questionnaire. Path analysis was
      employed. FINDINGS: Family sense of coherence had a direct impact on family and
      marital functioning and depressive symptoms among both couples. Family sense of
      coherence also mediated the effect of stress on family and marital functioning
      and depressive symptoms among the pregnant women. CONCLUSIONS: The study provides
      evidence that family sense of coherence plays a significant role in promoting
      family functioning and reducing depressive symptoms during the transition to
      parenthood. CLINICAL RELEVANCE: Knowledge of the impact of family sense of
      coherence in parental transition can better equip healthcare professionals for
      developing couple-based and culturally sensitive care to assist childbearing
      couples to cope with the stress and demands of the parental role, thereby
      promoting positive family functioning and well-being.

PMID- 24024739
TI  - Large ABCA3 and SFTPC deletions resulting in lung disease.
AB  - RATIONALE: Mutations in genes encoding proteins important in the function and
      metabolism of pulmonary surfactant are recognized causes of lung disease.
      Clinical genetic testing is available for these disorders, but children with
      phenotypes consistent with surfactant dysfunction and no identifiable mutations
      in the known causative genes have been reported. OBJECTIVES: To identify the
      mechanism(s) for lung disease in two children with the phenotype of surfactant
      dysfunction who had negative testing in clinical laboratories for gene mutations
      causing surfactant dysfunction. METHODS: Amplicons spanning multiple exons of
      candidate genes were generated by polymerase chain reaction and sequenced.
      MEASUREMENTS AND MAIN RESULTS: A 4,335-base deletion that included all of exon 12
      of the gene encoding member A3 of the adenosine triphosphate-binding cassette
      transporter was identified in a full-term infant with respiratory failure. A 333
      base deletion involving part of exon 4 and the adjacent intron of the gene
      encoding surfactant protein C was identified in a child with interstitial lung
      disease. CONCLUSIONS: Large deletions are a cause of surfactant dysfunction
      disorders and may need to be sought for specifically in children whose phenotypes
      suggest these syndromes but in whom clinical genetic testing is unrevealing.

PMID- 24024741
TI  - Molecular mechanisms of transcription elongation in archaea.

PMID- 24024743
TI  - Chronic periodontitis and erectile dysfunction.

PMID- 24024742
TI  - Nonparametric Bayesian evaluation of differential protein quantification.
AB  - Arbitrary cutoffs are ubiquitous in quantitative computational proteomics:
      maximum acceptable MS/MS PSM or peptide q value, minimum ion intensity to
      calculate a fold change, the minimum number of peptides that must be available to
      trust the estimated protein fold change (or the minimum number of PSMs that must
      be available to trust the estimated peptide fold change), and the "significant"
      fold change cutoff. Here we introduce a novel experimental setup and
      nonparametric Bayesian algorithm for determining the statistical quality of a
      proposed differential set of proteins or peptides. By comparing putatively
      nonchanging case-control evidence to an empirical null distribution derived from
      a control-control experiment, we successfully avoid some of these common
      parameters. We then apply our method to evaluating different fold-change rules
      and find that for our data a 1.2-fold change is the most permissive of the
      plausible fold-change rules. 

PMID- 24024744
TI  - Rapid and sensitive immunochromatographic strip for on-site detection of
      sulfamethazine in meats and eggs.
AB  - A rapid immunochromatographic (ICG) strip based on a conjugate of colloidal gold
      and monoclonal antibody (mAb) was developed for the rapid, sensitive, and on-site
      detection of sulfamethazine in meat and egg samples. The detection limit of the
      ICG strip is 2 ng/mL, and the assay can be completed in 10 min. A cross
      reactivity test indicated that the ICG strip was highly specific to
      sulfamethazine with no cross-reaction with sulfonamide compounds and other
      antibiotics. The results of the recovery test from meat and egg samples spiked
      with sulfamethazine were in good agreement with those obtained by the indirect
      competitive enzyme-linked immunosorbent assay. These results demonstrated that
      the ICG strip can be used as a rapid and qualitative tool for on-site screening
      of sulfamethazine in meat and egg samples. 

PMID- 24024745
TI  - Molecular dynamics of equilibrium and pressure-driven transport properties of
      water through LTA-type zeolites.
AB  - We consider an atomistic model to investigate the flux of water through thin
      Linde type A (LTA) zeolite membranes with differing surface chemistries. Using
      molecular dynamics, we have studied the flow of water under hydrostatic pressure
      through a fully hydrated LTA zeolite film (~2.5 nm thick) capped with hydrophilic
      and hydrophobic moieties. Pressure drops in the 50-400 MPa range were applied
      across the membrane, and the flux of water was monitored for at least 15 ns of
      simulation time. For hydrophilic membranes, water molecules adsorb at the zeolite
      surface, creating a highly structured fluid layer. For hydrophobic membranes, a
      depletion of water molecules occurs near the water/zeolite interface. For both
      types of membranes, the water structure is independent of the pressure drop
      established in the system and the flux through the membranes is lower than that
      observed for the bulk zeolitic material; the latter allows an estimation of
      surface barrier effects to pressure-driven water transport. Mechanistically, it
      is observed that (i) bottlenecks form at the windows of the zeolite structure,
      preventing the free flow of water through the porous membrane, (ii) water
      molecules do not move through a cage in a single-file fashion but rather exhibit
      a broad range of residence times and pronounced mixing, and (iii) a periodic
      buildup of a pressure difference between inlet and outlet cages takes place which
      leads to the preferential flow of water molecules toward the low-pressure cages.

PMID- 24024746
TI  - Mosaic chromosome 18q partial deletion syndrome with bilateral full-thickness
      corneal disease: surgical intervention and histopathology.
AB  - A 2-month-old boy diagnosed with a mosaic chromosome 18q partial deletion
      syndrome was referred for bilateral cloudy corneas. The abnormal metaphases had a
      terminal deletion of the long arm of chromosome 18 as clonal abnormality. The
      cytogenetics findings were 46,XY, del (18)(q21.2)[12]/46,XY[20]. Ocular findings
      included bilateral microcornea with dense opacification and unilateral iris and
      chorioretinal coloboma. Penetrating keratoplasty (PK) was performed on both eyes.
      Histopathology of the host corneal button showed complete loss of Bowman's layer,
      hyperkeratosis of the epithelium, stromal neovascularization, and leukocyte
      infiltration. Descemet's membrane and endothelium were irregular in both
      specimens. CD45 stain for leukocytes confirmed perivascular and epithelial
      leukocytes infiltration. Mosaic chromosome 18q deletion syndrome is a rare
      genetic abnormality with a variable phenotype - including ocular findings - and
      hence, warrants an ophthalmic evaluation and genetic counseling.

PMID- 24024747
TI  - A case of 22q11.2 deletion syndrome with Peters anomaly, congenital glaucoma, and
      heterozygous mutation in CYP1B1.
AB  - We read with interest the recent publication by Tarlan and colleagues 1
      describing a patient with 22q11.2 deletion syndrome and ocular features of right
      microphthalmia and left anterior segment dysgenesis. While anterior segment
      dysgenesis disorders are occasionally reported with 22q11.2 deletions, 2-5 this
      remains a rare association. We report here an 8-year-old patient with 22q11.2
      deletion syndrome and bilateral Peters anomaly with congenital glaucoma; in
      addition, our patient was found to have a single heterozygous mutation in CYP1B1,
      c.83C > T, p.(Ser28Trp).

PMID- 24024748
TI  - Whiskers-less HIV-protease: a possible way for HIV-1 deactivation.
AB  - BACKGROUND: Among viral enzymes, the human HIV-1 protease comprises the most
      interesting target for drug discovery. There are increasing efforts focused on
      designing more effective inhibitors for HIV-1 protease in order to prevent viral
      replication in AIDS patients. The frequent and continuous mutation of HIV-1
      protease gene creates a formidable obstacle for enzyme inhibition which could not
      be overcome by the traditional single drug therapy. Nowadays, in vitro and in
      silico studies of protease inhibition constitute an advanced field in biological
      researches. In this article, we tried to simulate protease-substrate complexes in
      different states; a native state and states with whiskers deleted from one and
      two subunits. Molecular dynamic simulations were carried out in a cubic box
      filled with explicit water at 37 degrees C and in 1atomsphere of pressure.
      RESULTS: Our results showed that whisker truncation of protease subunits causes
      the dimer structure to decrease in compactness, disrupts substrate-binding site
      interactions and changes in flap status simultaneously. CONCLUSIONS: Based on our
      findings we claim that whisker truncation even when applied to a single subunit,
      threats dimer association which probably leads to enzyme inactivation. We may
      postulate that inserting a gene to express truncated protease inside infected
      cells can interfere with protease dimerization. The resulted proteases would
      presumably have a combination of native and truncated subunits in their
      structures which exert no enzyme activities as evidenced by the present work. Our
      finding may create a new field of research in HIV gene therapy for protease
      inhibition, circumventing problems of drug resistance.

PMID- 24024749
TI  - Coexistence of KRT14 and KRT5 mutations in a Polish patient with epidermolysis
      bullosa simplex.

PMID- 24024750
TI  - Colesevelam in the treatment of hypercholesterolemia and hyperglycemia: a
      retrospective analysis from an ambulatory care medical network.
AB  - OBJECTIVE: To examine outcomes associated with colesevelam treatment among
      patients with hypercholesterolemia in real-world clinical practice. METHODS: This
      analysis was conducted as a retrospective, observational cohort study in an
      ambulatory-care medical network in Northern California. Patients with orders for
      colesevelam were identified in the electronic health record between January 2004
      and December 2011. The date of the first order during the study period was
      designated the index date. Patients were evaluated for the following eligibility
      criteria: a diagnosis of hypercholesterolemia, >=18 years of age at index date,
      baseline laboratory values <=3 months before the index date, >=12 months of
      treatment and follow-up, and no prior orders for colesevelam <=12 months before
      the index date. Patients who were pregnant during the study period were excluded.
      Changes in LDL-C and percentage of patients at LDL-C goal were examined. Among
      patients with diabetes mellitus (DM), changes in glycated hemoglobin (HBA1C) and
      percentage of patients at HBA1C goal were also examined. RESULTS: Overall, 468
      and 181 patients with hypercholesterolemia met the predefined inclusion criteria
      with treatment and follow-up through 12 and 24 months, respectively. LDL-C
      decreased significantly from baseline by a mean of 11.4 mg/dL and 15.7 mg/dL (P <
      0.0001, for each) at 12 and 24 months, respectively, and the percentages of
      patients at LDL-C goal increased by 13.9% and 21.0%. Among patients with DM and a
      baseline HBA1C >=8%, 113 and 39 had treatment and follow-up through 12 and 24
      months, respectively. HBA1C decreased significantly by a mean of 0.72% (P =
      0.0001) and 0.75% (P = 0.010) and 11.5% and 12.8% were at HBA1C goal at 12 and 24
      months, respectively. This study is limited by its retrospective and
      observational study design. CONCLUSIONS: Colesevelam treatment in a real-world
      setting was associated with improvements in LDL-C and HBA1C through 24 months of
      follow-up.

PMID- 24024751
TI  - Imaging of superoxide generation in the dopaminergic area of the brain in
      Parkinson's disease, using mito-TEMPO.
AB  - We report a new methodology for direct visualization of superoxide production in
      the dopaminergic area of the brain in Parkinson's disease, based on the redox
      cycle of mito-TEMPO, a blood-brain barrier-, cell-, and mitochondria-penetrating
      nitroxide derivative with superoxide scavenging properties and T1 magnetic
      resonance imaging (MRI) contrast. The experiments were conducted on healthy and 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. In healthy mice,
      the nitroxide-enhanced MRI signal was weak and short-lived (half-life ~ 40 s;
      duration ~ 80 s). The profile of the histograms indicated a high reducing
      activity of normal brain tissues against mito-TEMPO. In MPTP-treated mice, the
      nitroxide-enhanced MRI signal was strong and long-lived (half-life > 20 min;
      duration > 20 min), especially in the dopaminergic area of the brain. The
      histograms indicated a high oxidative activity in dopaminergic tissues of MPTP
      treated mice. The results show directly, on intact mammals, that superoxide is a
      major inducer and/or mediator of neurodegenerative damage in Parkinson's disease.
      The high oxidative status of brain tissue in Parkinson's disease was also
      confirmed on isolated tissue specimens, using total reducing capacity assay and
      ROS/RNS assay. 

PMID- 24024752
TI  - Pharmacological treatment of hemorrhoids: a narrative review.
AB  - INTRODUCTION: Hemorrhoid disease is the cause of most proctologic complaints and
      hundreds of medical and surgical therapies have been proposed to relieve
      symptoms. However, the role and the correct indication of medical treatments are
      still controversial. Further, the utility of conservative measures are rarely
      scientifically supported by adequate trials. AREAS COVERED: This narrative review
      is based on the search and analysis of full papers in English language selected
      from PubMed in the past 30 years using the following MeSH Editing: hemorrhoids,
      conservative treatment, medical treatment and hemorrhoids, pregnancy and
      hemorrhoids, thrombosed hemorrhoids, randomized trials and hemorrhoids,
      postoperative pain and hemorrhoids. EXPERT OPINION: Early stages (I/II degrees)
      of this disease could be effectively managed conservatively with several
      approaches as lifestyle changes, fiber supplement, topical ointments and
      phlebotonic drugs. The more advanced hemorrhoid stages (III/IV degrees) need some
      type of surgery, but medical therapy is still useful to minimize anal symptoms as
      a bridge-to-surgery treatment. Further, post-hemorrhoidectomy pain, hemorrhoidal
      crisis even in pregnancy could benefit from the adjunct of local and systemic
      medical treatment. This expert opinion, based also on long-lasting clinical
      practice, also supports the use of medical treatment in symptoms relief in
      patients with hemorrhoid disease.

PMID- 24024754
TI  - Nutraceutical properties of flour and tortillas made with an ecological
      nixtamalization process.
AB  - The traditional nixtamalization (TN) process, used for obtaining maize-based
      products, negatively affects bioactive compounds because of its highly alkaline
      pH. Recently, an ecological nixtamalization (EN) process has been developed that
      retains the pericarp and maintains the nejayote (wastewater) within the acidic
      neutral range. This study examines the effect of pH on the nutraceutical
      compounds (NC) of maize, such as polyphenolics and anthocyanins (ANT), as well as
      the effect on the antioxidant capacity (AC). The highest concentration of total
      phenolics (TP) in the maize kernel was found in the black and yellow genotypes,
      the highest concentration of ANT in the black genotypes, and the highest
      concentration of AC in the red and white genotypes. In the flour, TP levels were
      between 206 to 400 mg GA/100 g, ANT levels were 141 to 4107 mg cyanidin-3
      glucoside/kg, and AC levels were 2544 to 3001 mg AA/kg. In tortillas, TP levels
      were 255 to 319 mg GA/100 g, ANT levels were 32 to 3420 mg cyanidin-3
      glucoside/kg, and AC levels were from 1513 to 2695 mg AA/kg. The reduced loss of
      soluble solids, the pH, and the formation of compounds with proteins and
      carbohydrates from the EN process positively affected NC retention. 

PMID- 24024753
TI  - Standardizing nasal nitric oxide measurement as a test for primary ciliary
      dyskinesia.
AB  - RATIONALE: Several studies suggest that nasal nitric oxide (nNO) measurement
      could be a test for primary ciliary dyskinesia (PCD), but the procedure and
      interpretation have not been standardized. OBJECTIVES: To use a standard protocol
      for measuring nNO to establish a disease-specific cutoff value at one site, and
      then validate at six other sites. METHODS: At the lead site, nNO was
      prospectively measured in individuals later confirmed to have PCD by ciliary
      ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy
      and 146 disease control subjects, including individuals with asthma (n = 37),
      cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A
      disease-specific cutoff value was determined, using generalized estimating
      equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive
      individuals enrolled for evaluation for possible PCD. MEASUREMENTS AND MAIN
      RESULTS: At the lead site, nNO values in PCD (mean +/- standard deviation, 20.7
      +/- 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO
      values of healthy control subjects (304.6 +/- 118.8; 125.5-867.0 nl/min), asthma
      (267.8 +/- 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease
      (223.7 +/- 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic
      fibrosis (134.0 +/- 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff
      value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At
      six other sites, this cutoff identified 70 of the 71 (98.6%) participants with
      confirmed PCD. CONCLUSIONS: Using a standardized protocol in multicenter studies,
      nNO measurement accurately identifies individuals with PCD, and supports its
      usefulness as a test to support the clinical diagnosis of PCD.

PMID- 24024755
TI  - Surgical outcomes and patients' satisfaction with suprapubic phalloplasty.
AB  - INTRODUCTION: Many techniques, specifically forearm free flap phalloplasty, are
      used in penile reconstructive surgery. Although satisfying, a major disadvantage
      is the large, stigmatizing scar on the donor site, which leads many patients to
      explore alternatives. AIM: The aim of this study is to assess the outcomes and
      satisfaction of patients offered the choice between metaidioplasty, forearm free
      flap, and suprapubic phalloplasty. METHODS: Medical outcomes from the three-stage
      surgery were collected from the hospital files of 24 patients, who were also
      interviewed to assess their satisfaction, sexual function, and psychosexual well
      being. MAIN OUTCOME MEASURES: Medical complications, anthropometric measures, and
      interviewing questionnaire on satisfaction with appearance, sexual function, and
      psychological variables. RESULTS: Duration of surgery and of hospital stay was
      relatively short in the first (1 hour 30 minutes; 3 days) and last (1 hour 40
      minutes; 3 days) stage of surgery involving tissue expansion and neophallus
      release. These two stages were associated with few complications (17% and 4%
      minor complications respectively, 12% additional complications with
      hospitalization for the first stage). The second stage involving tubing was
      associated with longer surgery and hospital stay (2 hour 15 minutes; 5 days) and
      had more complications (54% minor complications and 29% requiring
      hospitalization) although fewer than one-step surgery. No loss of neophallus was
      reported. Overall, 95% of patients were satisfied with their choice of
      phalloplasty, 95% with the appearance, 81% with the length (Mean = 12.83 cm), and
      71% with the circumference (Mean = 10.83 cm) of their neophallus. Satisfactory
      appearance was significantly correlated (P < 0.01) with penile length (r = 0.69)
      and diameter (r = 0.77). Sexual satisfaction was significantly correlated with
      penile diameter (r = 0.758), frequency of orgasm (r = 0.71), perceived importance
      of voiding while standing (r = 0.56), presurgery satisfaction with sexuality (r =
      0.58), current masculine-feminine scale (r = 0.58), attractive-unattractive scale
      (r = 0.69), and happy-depressed scale (r = 0.63). CONCLUSION: Suprapubic
      phalloplasty, despite the lack of urethroplasty, offers an interesting
      alternative for patients concerned with the stigmatizing scar on the donor site.

PMID- 24024756
TI  - Benchmarking outcomes in resident-performed cataract surgery with toric
      intraocular lenses: comment.

PMID- 24024757
TI  - Randomised clinical trial: sodium alginate oral suspension is non-inferior to
      omeprazole in the treatment of patients with non-erosive gastroesophageal
      disease.
AB  - BACKGROUND: The burden of gastroesophageal reflux disease (GERD) is increasing in
      the Asia area and the majority of GERD patients have non-erosive reflux disease
      (NERD). AIM: To evaluate the efficacy and safety of sodium alginate suspension
      compared to omeprazole in adult subjects with NERD. METHODS: In this 4-week,
      double-blind, parallel study, 195 NERD subjects were randomised to one of two
      treatment groups: sodium alginate suspension 20 mL three times a day and
      omeprazole 20 mg once daily. The primary efficacy endpoint was the percentage of
      patients achieving adequate heartburn or regurgitation relief at day 28 assessed
      by patient diary. The secondary efficacy endpoints included percentage of
      patients achieving adequate heartburn or regurgitation relief, change from
      baseline of the Reflux Disease Questionnaire total score at day 14 and 28 from
      baseline, and patients' overall satisfaction. RESULTS: In this study, 183
      subjects were included in the intent-to-treat population, and 172 subjects were
      included in the per-protocol population. Non-inferiority of sodium alginate to
      omeprazole was demonstrated in the intent-to-treat population [difference, 2.7%
      (53.3% vs. 50.5%, P = 0.175), 95% lower confidence interval -11.9%, above the
      preset margin of -19%]. All of the secondary efficacy endpoints were comparable
      between two groups. The incidence of adverse event was relatively low and there
      was no difference between the two groups (5.4% vs. 5.5% for sodium alginate vs.
      omeprazole). No severe adverse event was noted in this study. CONCLUSION: The
      study showed that sodium alginate was as effective as omeprazole for symptomatic
      relief in patients with non-erosive reflux disease (Clinicaltrials.gov
      NCT01338077).

PMID- 24024758
TI  - Dementia care in eight European countries: developing a mapping system to explore
      systems.
AB  - PURPOSE: There is a knowledge gap with regard to the structure of the care and
      service system available to persons with dementia. This is very much a concern
      for nurses who are the main providers in the care of dementia. The study, a part
      of the "RightTimePlaceCare" project, describes the development and content of a
      mapping system aimed at exploring the content of care and service for persons
      with dementia and their informal caregiver throughout the disease trajectory. The
      usefulness of the mapping system is illustrated in describing the availability of
      care and service at the diagnostic stage, and at the institutional and palliative
      stages. DESIGN: A descriptive cross-country design concerning eight European
      countries differing in demographic composition and terms of long-term care
      provided is employed. METHODS: A modified consensus strategy was used to develop
      the mapping system and define the terminology. Thereafter, each country's mapping
      system was completed by its research group collecting country-specific
      information and using expert groups either as consultants or for completing the
      system. FINDINGS: The consensus procedure worked satisfactorily with regard to
      content and definitions, whereas assessing the availability and utilization of
      care and service was problematic. Some 50 types care and service activities were
      identified and defined and were categorized as follows: (a) screening, diagnostic
      procedures, and treatment of dementia; (b) outpatient care facilities; (c) care
      at home; (d) institutional care; (e) palliative care; (f) informal caregiving and
      supportive actions; and (g) civic activities. Care at home included the broadest
      range of activities; palliative care, informal caregiving, and supportive actions
      were the smallest range. CONCLUSIONS: The dementia care systems were found to be
      comprehensive and to emphasize home care. Activities aimed at transferring
      knowledge to informal caregivers, though highly important for home care, seemed
      less extensive. The mapping system appears useful from a nurse manager's
      standpoint for exploring the dementia care pathway. Comparisons between countries
      appear useful for developing the care system and for sharing information of how
      to perfect it. Further testing and development are needed regarding information
      on the availability and utilization of care and service activities. CLINICAL
      RELEVANCE: The mapping system can be useful in clarifying the dementia care
      system for those concerned, in helping nurse researchers and managers review and
      initiate evaluation and communicate with policy makers, as well as to ensure that
      providers use appropriate parts of the system. It can also be useful in national
      and international comparative studies.

PMID- 24024759
TI  - Impact of pharmacist antimicrobial dosing adjustments in septic patients on
      continuous renal replacement therapy in an intensive care unit.
AB  - BACKGROUND: Correct dosing of antimicrobial drugs in septic patients receiving
      continuous renal replacement therapy (CRRT) is complex. This study aimed to
      evaluate the effects of dosing adjustments performed by pharmacists on the length
      of intensive care unit (ICU) stay, ICU cost, and antimicrobial adverse drug
      events (ADEs). METHODS: A single-center, 2-phase (pre-/post-intervention) study
      was performed in an ICU of a university-affiliated hospital. Septic patients
      receiving CRRT in the post-intervention phase received a specialized
      antimicrobial dosing service from critical care pharmacists, whereas patients in
      the pre-intervention phase received routine medical care without involving
      pharmacists. The 2 phases were compared to evaluate the outcomes of pharmacist
      interventions. RESULTS: Pharmacists made 183 antimicrobial dosing adjustment
      recommendations for septic patients receiving CRRT. Changes in CRRT-related
      variables (116, 63.4%) were the most common risk factors for dosing errors, and
      beta-lactams (101, 55.2%) were the antimicrobials most commonly associated with
      dosing errors. Dosing adjustments were related to a reduced length of ICU stay
      from 10.7 +/- 11.1 days to 7.7 +/- 8.3 days (p = 0.037) in the intervention
      group, and to cost savings of $3525 (13,463 +/- 12,045 vs. 9938 +/- 8811, p =
      0.038) per septic patient receiving CRRT in the ICU. Suspected antimicrobial
      adverse drug events in the intervention group were significantly fewer than in
      the pre-intervention group (19 events vs. 8 events, p = 0.048). CONCLUSIONS: The
      involvement of pharmacists in antimicrobial dosing adjustments in septic patients
      receiving CRRT is associated with a reduced length of ICU stay, lower ICU costs,
      and fewer ADEs. Hospitals may consider employing clinical pharmacists in ICUs.

PMID- 24024760
TI  - Deep brain stimulation may improve quality of life in people with Parkinson's
      disease without affecting caregiver burden.
AB  - OBJECTIVE: This study aims to investigate the influence of deep brain stimulation
      (DBS) on caregiver burden and quality of life in Parkinson's disease. METHODS: A
      cross-sectional retrospective study utilizing the National Parkinson Foundation
      Quality Improvement Initiative clinical study was conducted. A group of 275
      patients who had undergone DBS for Parkinson's disease were extracted from 2916
      subjects who were included in this data base. The data were compared to an age,
      sex, and disease severity matched control group. A secondary analysis was then
      performed on two more control groups that were matched to account for presence or
      absence of motor fluctuations. The multidimensional caregiver strain index and
      Parkinson's disease quality-of-life questionnaire 39 summary index were compared.
      RESULTS: The multidimensional caregiver strain index did not differ between the
      DBS group (16.9 +/- 11.8) and a matched non-DBS group (16.1 +/- 17.6, p = 0.618).
      The quality-of-life index was, however, significantly better in the DBS group
      (28.9 +/- 15.6) than in the non-DBS group (32.3 +/- 17.6, p = 0.034). A secondary
      analysis revealed that the total caregiver strain score was lower in the no motor
      fluctuation control group than the other two groups (p < 0.05). Regression
      analysis revealed significant relationships between the quality-of-life index and
      caregiver strain index total scores (p < 0.001), between caregiver strain index
      total score and age at surgery (p = 0.027), and also between the interval since
      surgery (p = 0.048). CONCLUSIONS: Although there were several limitations to this
      study, DBS seems to improve quality of life without significantly increasing
      caregiver burden.

PMID- 24024761
TI  - Cation-cation interactions in [(UO2)2(OH)n](4-n) complexes.
AB  - The structures and bonding of gas-phase [(UO2)2(OH)n](4-n) (n = 2-6) complexes
      have been studied using density functional theory (DFT), MP2, and CCSD(T) methods
      with particular emphasis on ground state structures featuring cation-cation
      interactions (CCIs) between the uranyl groups. An interesting trend is observed
      in the stabilities of members of this series of complexes. The structures of
      [(UO2)2(OH)2](2+), [(UO2)2(OH)4], and [(UO2)2(OH)6](2-) featuring CCIs are found
      at higher energies (by 3-27 kcal/mol) in comparison to their conventional MU2
      dihydroxo structures. In contrast, the CCI structures of [(UO2)2(OH)3](+) and
      [(UO2)2(OH)5](-) are respectively degenerate with and lower in energy than the
      structures with the MU2-dihydroxo format. The origin of this trend lies in the
      symmetry-based need to balance the coordination numbers and effective atomic
      charges of each uranium center. The calculated IR vibrational frequencies provide
      signature probes that can be used in differentiating the low-energy structures
      and in experimentally confirming the existence of the structures featuring CCIs. 

PMID- 24024762
TI  - Early achievements in cardiovascular care as reflected in the Journal of Internal
      Medicine.
AB  - This review mirrors progress in cardiovascular medicine as reflected by
      scientific contributions published in the Journal of Internal Medicine (from
      1989), Acta Medica Scandinavica (from 1919 until 1989) and Nordiskt Medicinskt
      Arkiv (before 1919). A total of 149 articles were identified within this field
      since the first, published work in this field 1877-1970. The latter year was set
      as and end for the review since this was the year the first contribution by the
      author of this review was published in the journal. To cope with the large number
      individual publications related to different aspects of cardiovascular medicine
      were grouped together into fields in which Scandinavian contributions were
      pioneering or for other reasons of particular interest. These articles were
      briefly summarized together with some information of the author(s) and the
      contributions were put into the perspective of subsequent importance and/or
      scientific and clinical development. Among topics with insightful contributions
      published in the journal are electrophysiology, diagnostic techniques including
      standardization, endurance exercise and the heart, electrocardiography,
      myocardial infarction, atrio-ventricular block and cardiac pacing. Some of these
      early contributions were indeed, considering the methods available at the time
      for the investigations impressive and many predictions truly insightful and
      imaginative. Other contributions may, at least by the present day reader, seem
      somewhat odd. 

PMID- 24024763
TI  - Accumulation of the mycotoxin patulin in the presence of gluconic acid
      contributes to pathogenicity of Penicillium expansum.
AB  - Penicillium expansum, the causal agent of blue mold rot, causes severe
      postharvest fruit maceration through secretion of D-gluconic acid (GLA) and
      secondary metabolites such as the mycotoxin patulin in colonized tissue. GLA
      involvement in pathogenicity has been suggested but the mechanism of patulin
      accumulation and its contribution to P. expansum pathogenicity remain unclear.
      The roles of GLA and patulin accumulation in P. expansum pathogenicity were
      studied using i) glucose oxidase GOX2-RNAi mutants exhibiting decreased GOX2
      expression, GLA accumulation, and reduced pathogenicity; ii) IDH-RNAi mutants
      exhibiting downregulation of IDH (the last gene in patulin biosynthesis), reduced
      patulin accumulation, and no effect on GLA level; and iii) PACC-RNAi mutants
      exhibiting downregulation of both GOX2 and IDH that reduced GLA and patulin
      production. Present results indicate that conditions enhancing the decrease in
      GLA accumulation by GOX2-RNAi and PACC-RNAi mutants, and not low pH, affected
      patulin accumulation, suggesting GLA production as the driving force for further
      patulin accumulation. Thus, it is suggested that GLA accumulation may modulate
      patulin synthesis as a direct precursor under dynamic pH conditions modulating
      the activation of the transcription factor PACC and the consequent pathogenicity
      factors, which contribute to host-tissue colonization by P. expansum. 

PMID- 24024765
TI  - Calling all authors.

PMID- 24024764
TI  - Functional analysis of a tannic-acid-inducible and hypoviral-regulated small heat
      shock protein Hsp24 from the chestnut blight fungus Cryphonectria parasitica.
AB  - A small heat-shock protein gene, CpHsp24, of Cryphonectria parasitica was
      selected based on its expression pattern, which showed that it was tannic acid
      inducible and that its induction was severely hampered by a hypovirus. The
      predicted protein sequence of CpHsp24 consisted of a hallmark alpha-crystalline
      domain flanked by a variable N-terminal and a short C-terminal region. Disruption
      of CpHsp24 resulted in a slow growth rate under standard growth conditions. The
      CpHsp24-null mutant showed enhanced sensitivity to heat shock, which was
      consistent with Northern and Western analyses displaying the heat-shock induction
      of the CpHsp24 gene and protein, respectively. Virulence tests on the excised
      bark revealed a severe decrease in the necrotic area of the CpHsp24-null mutant.
      When the hypovirus was transferred, virus-containing CpHsp24-null progeny
      displayed severely retarded growth patterns with hypovirulent characteristics of
      reduced pigmentation and sporulation. Because the tannic-acid-inducible and
      hypoviral-suppressible expression and the severely impaired virulence are also
      characteristics of the laccase3 gene (lac3), lac3 expression in the CpHsp24-null
      mutant was also examined. The resulting lac3 induction was severely affected in
      the CpHsp24-null mutant, suggesting that CpHsp24 is important for lac3 induction
      and that CpHsp24 may act as a molecular chaperone for the lac3 protein. 

PMID- 24024767
TI  - Characteristics of eating habits and physical activity in relation to body mass
      index among adolescents.
AB  - OBJECTIVE: To assess eating habits and the level of physical activity in
      adolescents and develop a predictive model for the body mass index (BMI) based on
      these variables. DESIGN: In this cross-sectional study, eating habits and the
      level of physical activity were assessed using a questionnaire validated in
      adolescents. Body mass and height collected during the last annual checkup were
      extracted from personal medical records. SUBJECTS: The sample included 330 boys
      and 377 girls (mean age 15.8 +/- 0.2 years) who were first-year high school
      students in the city of Belgrade, Serbia. MEASURES: Responses to each of the 14
      questions about eating habits and 6 questions about physical activity were scored
      from the least (0) to the most (3) desired behaviors. These ratings were then
      averaged to arrive to an aggregate score for each domain. The BMI was calculated
      according to the standard method. A series of regression analyses was performed
      to derive the best model for predicting BMI in boys and girls based on individual
      eating habits and physical activity items, first separately and then combined.
      RESULTS: In the sample, 24.5% of boys and 9.5% of girls were overweight or obese.
      Girls' eating habits were better than boys (mean aggregate score 2.3 +/- 0.3 and
      2.1 +/- 0.3, respectively, p < 0.001), whereas the level of physical activity was
      greater in boys than girls (2.1 +/- 0.6 vs 1.9 +/- 0.6, p < 0.001). The
      differences between boys and girls in the BMI, eating habits, and physical
      activity remained significant after controlling for their knowledge about healthy
      eating and education level of their parents. Eating habits were a better
      predictor of BMI than physical activity, particularly in boys (R (2) = 0.13 vs R
      (2) = 0.02) compared to girls (R (2) = 0.04 vs R (2) = 0.01). Combining eating
      habits and physical activity in the multivariate model of BMI resulted in a
      better predictive accuracy in boys (R (2) = 0.17) but not girls (R (2) = 0.04).
      CONCLUSIONS: Eating habits and physical activity differ between adolescent boys
      and girls and can predict BMI, particularly in boys. The results suggest the need
      to develop gender-specific programs for promoting healthy lifestyle among
      adolescents in our country.

PMID- 24024766
TI  - Vitamin D deficiency in cord plasma from multiethnic subjects living in the
      tropics.
AB  - BACKGROUND: Vitamin D deficiency is commonly reported in high-latitude areas and
      in dark-pigmented individuals. However, nothing is known about vitamin D in cord
      blood from multiethnic subjects living in the tropics. OBJECTIVE: Our study
      objective was to determine the prevalence of vitamin D deficiency in summer and
      winter in cord blood from multiethnic individuals in Hawai'i where sufficient sun
      irradiance occurs year-round for cutaneous vitamin D production. METHODS: 25
      Hydroxyvitamin D (25(OH)D) levels were quantified by enzyme immunoassay in 100
      cord plasma samples from apparently healthy full-term newborns and their mothers.
      Stratification was performed by birth season and ethnicity. RESULTS: Mean 25(OH)D
      levels were 24.5 ng/mL (9.1-68.3 ng/mL). Overall, 28% of samples were vitamin D
      deficient (<20 ng/mL) and 50% were insufficient (20-30 ng/mL). 25(OH)D levels
      (ng/mL) were highest in Caucasians (30.5, n = 19), followed by Asians (25.1, n =
      43), Hispanics (21.5, n = 3), Pacific Islanders (20.0, n = 25), and African
      Americans (19.6, n = 2). Differences among groups were significant (p = 0.008).
      Cord plasmas from summer versus winter were higher overall (p = 0.001) and among
      Asians (p = 0.0003). Seasonal changes were correlated with sun irradiance overall
      (r = 0.43, p = 0.0001), among Caucasians (r = 0.45, p = 0.05), and among Asians
      (r = 0.45, p = 0.0001). CONCLUSION: Our results suggest that prenatal supplement
      recommendations of 400 IU vitamin D/day do not protect against vitamin D
      deficiency, even in subjects living in the tropics where ample sun irradiance
      exists for cutaneous vitamin D synthesis. The high prevalence of vitamin D
      deficiency we observed emphasizes the necessity for regular 25(OH)D monitoring,
      particularly during pregnancy and lactation, in dark-pigmented individuals, and
      during winter months.

PMID- 24024768
TI  - Triglyceride recrystallized phytosterols in fat-free milk improve lipoprotein
      profiles more than unmodified free phytosterols in hypercholesterolemic men and
      women.
AB  - OBJECTIVE: Foods incorporating plant sterols (PS) consistently decrease serum low
      density lipoprotein cholesterol (LDL-C), although results vary depending on the
      PS form and food matrix. The objective was to study the effect of a novel
      triglyceride-recrystallized phystosterol (TRP) incorporated into fat-free milk on
      markers of cardiovascular risk compared to unmodified free sterols alone in the
      same fat-free milk. METHODS: Hypercholesterolemic men and women (n = 13 males/7
      females; 56 +/- 10 years; body mass index 27.3 +/- 5.9 kg/m(2)) participated in 3
      sequential 4-week phases of 480 mL milk consumption. During phase 1 (control) all
      subjects consumed 2% milk containing no PS, followed by phase 2 with fat-free
      milk containing free PS (2 g/d fPS) and phase 3 with fat-free milk with TRP (2
      g/d). After each phase, determinations of lipoprotein cholesterol distribution,
      particle concentration via nuclear magnetic resonance (NMR), apolipoproteins,
      inflammatory markers, and fat-soluble dietary antioxidants were made. RESULTS:
      Body mass, body composition, dietary energy and macronutrients, and physical
      activity were unaffected throughout the study. Compared to the control 2% milk,
      LDL-C was significantly (p < 0.05) decreased by fPS (-9.1%) and was further
      decreased by TRP (-15.4%); reductions with TRP were significantly greater. Total
      LDL particle concentration was decreased to a greater extent after TRP (-8.8%)
      than fPS (-4.8%; p < 0.05). Only TRP significantly decreased serum levels of
      apolipoprotein B (apoB; -6%), interleukin-8 (IL-8; -11%) and monocyte chemotactic
      protein-1 (MCP-1; -19%). Plasma alpha- and gamma-tocopherols and carotenoids,
      normalized to cholesterol, remained unchanged throughout the study with the
      exception that beta-carotene was lowered by 18%. CONCLUSION: In summary, TRP in
      fat-free milk may provide cardiovascular benefits beyond that of fPS by inducing
      more substantial decreases in LDL cholesterol and particle concentration,
      associated with declines in markers of vascular inflammation.

PMID- 24024769
TI  - Chromium nicotinate has no effect on insulin sensitivity, glycemic control, and
      lipid profile in subjects with type 2 diabetes.
AB  - OBJECTIVE: To investigate the effect of chromium nicotinate supplementation on
      insulin sensitivity, glycemic control, and lipid profile in subjects with type 2
      diabetes. MATERIALS AND METHODS: In a double-blind clinical trial, 56 overweight
      individuals with type 2 diabetes were randomized into 3 groups: placebo (NC0), 50
      MUg (NC50), and 200 MUg (NC200) of chromium as chromium nicotinate. Chromium
      status, sensitivity to insulin, glycemic control, and lipid profile were assessed
      at the beginning of the study and 45 days and 90 days after. RESULTS: In the
      beginning, most subjects showed low concentrations of serum chromium (71.88%),
      regular levels of urinary chromium (80.65%), and insulin resistance (73.80%). The
      serum chromium concentrations did not differ among the groups over time (p =
      0.2549). The changes in serum chromium and urine concentrations did not relate to
      changes in fasting glucose (p > 0.05). At 90 days of intervention, there was no
      significant difference between groups in fasting glucose, glycosylated
      hemoglobin, homeostasis model assessment insulin resistance (HOMA-IR), total
      cholesterol, and low-density lipoprotein (LDL); there was increase in homeostasis
      model assessment beta-cell function (HOMA-beta; p = 0.0349) and high-density
      lipoprotein (HDL; p = 0.0425) in the NC0 group and a reduction of triglycerides
      in the NC0 (p = 0.0177) and NC50 (p = 0.0336) groups. CONCLUSION: Supplementation
      at 50 and 200 MUg of chromium as chromium nicotinate did not promote glycemic
      control, increase insulin sensitivity, or change the lipid profile of subjects
      with diabetes.

PMID- 24024771
TI  - Weight loss is more important than the diet type in improving adiponectin levels
      among overweight/obese adults.
AB  - OBJECTIVE: The study objective was to compare the effect of a standard calorie-
      and fat-restricted diet (STD-D) and a calorie- and fat-restricted lacto-ovo
      vegetarian diet (LOV-D) on total and high-molecular-weight (HMW) adiponectin
      levels after 6 months of behavioral intervention. DESIGN: This study is an
      ancillary study to a randomized clinical trial. SUBJECTS: Subjects included 143
      overweight/obese adults (STD-D = 79; LOV-D = 64). INTERVENTION: Both groups
      received the same standard behavioral intervention; the only difference was that
      LOV-D participants were instructed to eliminate meat, poultry, and fish from
      their diet. MEASURES: Weight, dietary intake with the 3-day food diary, and total
      and HMW adiponectin levels were measured. RESULTS: Both groups significantly
      increased total (STD-D +7.2 +/- 17.8%; LOV-D +9.4 +/- 21.8%) and HMW adiponectin
      levels (STD-D +18.5 +/- 32.9%; LOV-D +15.8 +/- 34.5%; ps < 0.05) with no
      significant differences between the groups. We found significant associations
      between weight loss and increases in total (beta (SE) = -.071(.27); p = 0.003)
      and HMW adiponectin (beta (SE) = -1.37(.47); p = 0.001) levels independent of the
      diet type. Weight loss at the higher quartile was associated with improvements of
      adiponectin levels (p < 0.05). CONCLUSION: Weight loss was associated with
      increased total and HMW adiponectin levels regardless of the diet type. Enhancing
      weight loss may be a means to improve adiponectin levels.

PMID- 24024772
TI  - Acute effect of oatmeal on subjective measures of appetite and satiety compared
      to a ready-to-eat breakfast cereal: a randomized crossover trial.
AB  - OBJECTIVE: The physicochemical properties of soluble oat fiber (beta-glucan)
      affect viscosity-dependent mechanisms that influence satiety. The objective of
      this study was to compare the satiety impact of oatmeal with the most widely sold
      ready-to-eat breakfast cereal (RTEC) when either was consumed as a breakfast
      meal. METHODS: Forty-eight healthy individuals >=18 years of age were enrolled in
      a randomized crossover trial. Following an overnight fast, subjects consumed
      either oatmeal or RTEC in random order at least a week apart. The breakfasts were
      isocaloric and contained 363 kcal (250 kcal cereal, 113 kcal milk). Visual
      analogue scales measuring appetite and satiety were completed before breakfast
      and throughout the morning. The content and physicochemical properties of oat
      beta-glucan were determined. Appetite and satiety responses were analyzed by area
      under the curve (AUC). Physicochemical properties were analyzed using t tests.
      RESULTS: Oatmeal, higher in fiber and protein but lower in sugar than the RTEC,
      resulted in greater increase in fullness (AUC: p = 0.005 [120 minute: p = 0.0408,
      180 minute: p = 0.0061, 240 minute: p = 0.0102]) and greater reduction in hunger
      (AUC: p = 0.0009 [120 minute: p = 0.0197, 180 minute: p = 0.0003, 240 minute: p =
      0.0036]), desire to eat (AUC: p = 0.0002 [120 minute: p = 0.0168, 180 minute: p <
      0.0001, 240 minute: p = 0.0022]), and prospective intake (AUC: p = 0.0012 [120
      minute: p = 0.0058, 180 minute: p = 0.006, 240 minute: p = 0.0047]) compared to
      the RTEC. Oatmeal had higher beta-glucan content, higher molecular weight (p <
      0.0001), higher viscosity (p = 0.025), and larger hydration spheres (p = 0.0012)
      than the RTEC. CONCLUSION: Oatmeal improves appetite control and increases
      satiety. The effects may be attributed to the viscosity and hydration properties
      of its beta-glucan content.

PMID- 24024770
TI  - Dairy in adulthood: from foods to nutrient interactions on bone and skeletal
      muscle health.
AB  - The risk of fragility fractures exponentially increases with aging. Reduced mass
      and strength of both bone in osteoporosis and skeletal muscle in sarcopenia play
      a key role in the age-related incidence of fragility fractures. Undernutrition is
      often observed in the elderly, particularly in those subjects experiencing
      osteoporotic fractures, more likely as a cause than a consequence. Calcium (Ca),
      inorganic phosphate (Pi), vitamin D, and protein are nutrients that impact bone
      and skeletal muscle integrity. Deficiency in the supply of these nutrients
      increases with aging. Dairy foods are rich in Ca, Pi, and proteins and in many
      countries are fortified with vitamin D. Dairy foods are important souces of these
      nutrients and go a long way to meeting the recommendations, which increase with
      aging. This review emphaszes the interactions between these 4 nutrients, which,
      along with physical activity, act through cellular and physiological pathways
      favoring the maintenance of both bone and skeletal muscle structure and function.

PMID- 24024774
TI  - Design strategies for P-containing fuels adaptable CeO2-MoO3 catalysts for
      DeNO(x): significance of phosphorus resistance and N2 selectivity.
AB  - Phosphorus compounds from flue gas have a significant deactivation effect on
      selective catalytic reduction (SCR) DeNOx catalysts. In this work, the effects of
      phosphorus over three catalysts (CeO2, CeO2-MoO3, and V2O5-MoO3/TiO2) for NH3-SCR
      were studied, and characterizations were performed aiming at a better
      understanding of the behavior and poisoning mechanism of phosphorus over SCR
      catalysts. The CeO2-MoO3 catalyst showed much better catalytic behavior with
      respect to resistance to phosphorus and N2 selectivity compared with V2O5
      MoO3/TiO2 catalyst. With addition of 1.3 wt % P, the SCR activity of V2O5
      MoO3/TiO2 decreased dramatically at low temperature due to the impairment of
      redox property for NO oxidation; meanwhile, the activity over CeO2 and CeO2-MoO3
      catalysts was improved. The superior NO oxidation activity contributes to the
      activity over P-poisoned CeO2 catalyst. The increased surface area and abundant
      acidity sites contribute to excellent activity over CeO2-MoO3 catalyst. As the
      content of P increased to 3.9 wt %, the redox cycle over CeO2 catalyst (2CeO2 <->
      Ce2O3 + O*) was destroyed as phosphate accumulated, leading to the decline of SCR
      activity; whereas, more than 80% NOx conversion and superior N2 selectivity were
      obtained over CeO2-MoO3 at T > 300  degrees C. The effect of phosphorus was
      correlated with the redox properties of SCR catalyst for NH3 and NO oxidation. A
      spillover effect that phosphate transfers from Ce to Mo in calcination was
      proposed. 

PMID- 24024773
TI  - Vitamin A supplementation and serum Th1- and Th2-associated cytokine response in
      women.
AB  - AIMS AND BACKGROUND: T helper (Th)1/Th2 immune response has been linked to
      obesity-related immune disorders. It has been proven that retinoid active
      derivates improve immunity via regulating Th1/Th2 balance. However, there is not
      a well-identified report of direct effect of vitamin A on Th1/Th2 balance in
      obesity. The present study aimed to investigate the possible role of vitamin A on
      serum Th1/Th2 response in obese women. MATERIALS AND METHODS: A randomized double
      blind placebo-controlled trial was conducted on 84 obese (n = 56; body mass index
      [BMI] 30-39.9 kg/m(2)) and nonobese (n = 28; BMI 18.5-24.9 kg/m(2)) women. Obese
      women were randomly allocated to receive either vitamin A (retinyl palmitate
      25,000 IU/d) or placebo. Nonobese women also received 25,000 IU/d retinyl
      palmitate. Anthropometric variables were assessed and serum interleukin (IL)
      1beta, tumor necrosis factor (TNF)-alpha, IL-4, and IL-13 were analyzed before
      and 4 months after intervention. RESULTS: Vitamin A treatment significantly
      reduced serum concentrations of IL-1beta in obese vitamin A-treated subjects
      (from 3.58 +/- 0.36 to 2.45 +/- 0.23 pg/ml, p < 0.006). Serum concentrations of
      IL-4 and IL-13 were also reduced in obese and nonobese vitamin A-treated subjects
      (p < 0.05). A significant reduction in IL-1beta/IL-4 ratio in the obese vitamin A
      treated group was also observed (p = 0.03). CONCLUSIONS: Decline in serum
      concentrations of IL-1beta and IL-1beta/IL-4 ratio in obese women suggests that
      vitamin A is capable of regulating the immune system and possibly reducing the
      risk of autoimmune disease in this group. Further studies are needed to explore
      the possible underlying mechanisms.

PMID- 24024775
TI  - Integrated approach to structure-based enzymatic drug design: molecular modeling,
      spectroscopy, and experimental bioactivity.

PMID- 24024776
TI  - Microspheres targeted with a mesothelin antibody and loaded with doxorubicin
      reduce tumor volume of human mesotheliomas in xenografts.
AB  - BACKGROUND: Malignant mesotheliomas (MMs) are chemoresistant tumors related to
      exposure to asbestos fibers. The long latency period of MM (30-40 yrs) and
      heterogeneity of tumor presentation make MM difficult to diagnose and treat at
      early stages. Currently approved second-line treatments following surgical
      resection of MMs include a combination of cisplatin or carboplatin (delivered
      systemically) and pemetrexed, a folate inhibitor, with or without subsequent
      radiation. The systemic toxicities of these treatments emphasize the need for
      more effective, localized treatment regimens. METHODS: Acid-prepared mesoporous
      silica (APMS) microparticles were loaded with doxorubicin (DOX) and modified
      externally with a mesothelin (MB) specific antibody before repeated
      intraperitoneal (IP) injections into a mouse xenograft model of human peritoneal
      MM. The health/weight of mice, tumor volume/weight, tumor necrosis and cell
      proliferation were evaluated in tumor-bearing mice receiving saline, DOX high
      (0.2 mg/kg), DOX low (0.05 mg/kg), APMS-MB, or APMS-MB-DOX (0.05 mg/kg) in
      saline. RESULTS: Targeted therapy (APMS-MB-DOX at 0.05 mg/kg) was more effective
      than DOX low (0.05 mg/kg) and less toxic than treatment with DOX high (0.2
      mg/kg). It also resulted in the reduction of tumor volume without loss of animal
      health and weight, and significantly decreased tumor cell proliferation. High
      pressure liquid chromatography (HPLC) of tumor tissue confirmed that APMS-MB-DOX
      particles delivered DOX to target tissue. CONCLUSIONS: Data suggest that targeted
      therapy results in greater chemotherapeutic efficacy with fewer adverse side
      effects than administration of DOX alone. Targeted microparticles are an
      attractive option for localized drug delivery.

PMID- 24024777
TI  - Sodium dodecyl sulfate adsorption onto positively charged surfaces: monolayer
      formation with opposing headgroup orientations.
AB  - The adsorption and structure of sodium dodecyl sulfate (SDS) layers onto
      positively charged films have been monitored in situ with vibrational sum
      frequency-generation (SFG) spectroscopy and surface plasmon resonance (SPR)
      sensing. Substrates with different charge densities and polarities used in these
      studies include CaF2 at different pH values as well as allylamine and heptylamine
      films deposited onto CaF2 and Au substrates by radio frequency glow discharge
      deposition. The SDS films were adsorbed from aqueous solutions ranging in
      concentration from 0.067 to 20 mM. In general the SFG spectra exhibited well
      resolved CH and OH peaks. However, at SDS concentrations between 1 and 8 mM the
      SFG CH and OH intensities decreased close to background levels. Combined data
      sets from molecular conformation, orientation, and order sensitive SFG with mass
      sensitive SPR suggest that the observed changes in SFG intensities above 0.2 mM
      are related to structural arrangements in the SDS layer. A model is proposed
      where the SFG intensity minimum between 1 and 8 mM is associated with a monolayer
      containing two headgroup orientations, one pointing toward the substrate and one
      pointing toward the solution phase. The SFG peaks observed at concentrations
      below 0.2 mM are dominated by the presence of adsorbed contaminants such as fatty
      alcohols (e.g., dodecanol), which are more surface active than SDS. As SDS
      solution concentration is increased above 1 mM SDS molecules are incorporated in
      the surface layer, with dodecanol continuing to be present in the surface layer
      for solution concentrations up to at least the critical micelle concentration. 

PMID- 24024778
TI  - Comparative proteomics reveals a role for seed storage protein AmA1 in cellular
      growth, development, and nutrient accumulation.
AB  - Seed storage proteins are known to be utilized as carbon and nitrogen source for
      growing seedlings and thus are considered as potential candidates for nutritional
      improvement. However, their precise function remains unknown. We have earlier
      shown that ectopic expression of a seed storage protein, AmA1, leads to increase
      in protein besides high tuber yield in potato. To elucidate the AmA1-regulated
      molecular mechanism affecting increased protein synthesis, reserve accumulation,
      and enhanced growth, a comparative proteomics approach has been applied to tuber
      life-cycle between wild-type and AmA1 potato. The differential display of
      proteomes revealed 150 AmA1-responsive protein spots (ARPs) that change their
      intensities more than 2.5-fold. The LC-ESI-MS/MS analyses led to the
      identification of 80 ARPs presumably associated with cell differentiation,
      regulating diverse functions, viz., protein biogenesis and storage, bioenergy and
      metabolism, and cell signaling. Metabolome study indicated up-regulation of amino
      acids paralleling the proteomics analysis. To validate this, we focused our
      attention on anatomical study that showed differences in cell size in the cortex,
      premedullary zone and pith of the tuber, coinciding with AmA1 expression and
      localization. Further, we interrogated the proteome data using one-way analysis
      of variance, cluster, and partial correlation analysis that identified two
      significant protein modules and six small correlation groups centered around
      isoforms of cysteine protease inhibitor, actin, heat shock cognate protein 83 and
      14-3-3, pointing toward AmA1-regulated overlapping processes of protein
      enhancement and cell growth perhaps through a common mechanism of function. A
      model network was constructed using the protein data sets, which aim to show how
      target proteins might work in coordinated fashion and attribute to increased
      protein synthesis and storage reserve accumulation in AmA1 tubers on one hand and
      organ development on the other. 

PMID- 24024779
TI  - Intra-sac portion of the lacrimal canaliculus.
AB  - PURPOSE: The aim of this study was to examine the length and diameter of the
      intra-sac portion of the lacrimal canaliculus and to propose a modified
      functional valve model at the common internal ostium. METHODS: We examined 14
      eyelid and orbital specimens from 10 cadavers (seven right, seven left; aged 45
      85 years at death), fixed in 10% buffered formalin. Sliced specimens were
      dehydrated and embedded in paraffin, cut into 7 MUm thickness sections, and
      stained with Masson's trichrome. We then measured the length and diameter of the
      intra-sac portion of the lacrimal canaliculus. RESULTS: The average length of the
      intra-sac portion of the lacrimal canaliculus was 1344.9 MUm (range, 920.2-1821.5
      MUm), and its average diameter was 287.5 MUm (range, 199.1-523.3 MUm).
      CONCLUSION: The intra-sac portion of the lacrimal canaliculus had an average
      length and diameter of 1344.9 MUm and 287.5 MUm, respectively. The lacrimal sac
      mucosa changes its thickness with autonomic stimulation, and the length and
      diameter of the intra-sac portion of the lacrimal canaliculus is likely changed
      concurrently. The long length and small diameter of the intra-sac lacrimal
      canaliculus presumably contribute to it acting as an autonomic functional valve
      at the common internal ostium.

PMID- 24024780
TI  - The microbiological spectrum and antibiotic sensitivity profile of extubated
      silicone stents following dacryocystorhinostomy.
AB  - PURPOSE: We aim to report the microbiological spectrum of organisms cultured from
      extubated silicone stents after a dacryocystorhinostomy and their antibiotic
      sensitivity patterns. STUDY DESIGN: Prospective interventional study. METHODS: 50
      silicone stents of 50 consecutive patients who underwent either external or
      endonasal dacryocystorhinostomy were enrolled for the study. All the stents were
      retrieved under endoscopic guidance from the nasal cavity at 3 months following
      surgery. All the tubes were immediately inoculated onto blood agar, chocolate
      agar, brain-heart infusion broth, Saboraud's dextrose agar and potato dextrose
      agar. Data collected and analyzed include demographics, diagnosis, type of
      dacryocystorhinostomy and the microbiological profile. The culture results,
      organisms isolated and their antibiotic sensitivity were studied. RESULTS: The
      mean age of patients at the time of dacyrocystorhinostomy was 34.4 years.
      Bacterial growth was noted in 88% (44/50) of all the stents cultured, whereas 60%
      (30/50) grew fungi and 6% (3/50) showed sterile cultures. 48% (24/50) of the
      stents showed mixed bacterial and fungal isolates. Among the fungal isolates,
      Aspergillus species accounted for 66.6% (20/30) followed by Fusarium species,
      which were seen in 26.6% (8/30). Among the bacterial isolates, gram negative
      organisms were the most common seen in 54.5% (24/44) and the commonest species
      isolated was Pseudomonas aeruginosa from 27% (12/44) of the stents.
      Staphylococcus aureus was the commonest gram positive isolate accounting for 18%
      of all the bacterial isolates. Gram positive organisms were commonly sensitive to
      cephalosporins and vancomycin whereas gram negative organisms were sensitive to
      quinolones and aminoglycosides. The surgical success rate was 96% (48/50).
      CONCLUSIONS: Fungal isolates were cultured from significant number of stents
      retrieved following dacryocystorhinostomy. Gram negative organisms are more
      common as compared to the gram positive. The organisms isolated were not found to
      influence the success of dacryocystorhinostomy.

PMID- 24024781
TI  - Large frontal osteoid osteoma with orbital extension.
AB  - Osteoid osteomas are benign bone tumors first described by Jaffe in 1935. They
      are usually located within the cortex of long bones in the lower extremities.
      These types of tumors are rare in the skull area, representing less than 1% of
      benign cases. We present a case of a large osteoid osteoma producing proptosis
      and requiring a frontal sinusotomy with excision of the mass.

PMID- 24024782
TI  - Dacryoendoscopic findings of lacrimal passage with congenital punctal atresia.
AB  - A 43-year-old woman presented with epiphora caused by upper and lower congenital
      punctual atresia with papilla. She underwent 2-snip punctoplasty and intubation
      under local anaesthesia. During the surgery, a dacryoendoscopic examination was
      performed. After performing the punctoplasty, the lacrimal passage was confirmed
      to have complete canalisation to the nasal cavity. Both upper and lower
      canaliculi appeared to be narrower and had difficult expansion compared with
      canaliculi in congenital nasolacrimal duct obstruction or primary acquired
      nasolacrimal duct obstruction without canalicular stenosis. The lacrimal sac and
      the nasolacrimal duct also showed complete canalization with normal colour.

PMID- 24024784
TI  - The top prescription drugs of 2012 globally: biologics dominate, but small
      molecule CNS drugs hold on to top spots.

PMID- 24024786
TI  - Postprandial lipid profile in patients with type 2 diabetes.

PMID- 24024783
TI  - Allosteric interactions at adenosine A(1) and A(3) receptors: new insights into
      the role of small molecules and receptor dimerization.
AB  - The purine nucleoside adenosine is present in all cells in tightly regulated
      concentrations. It is released under a variety of physiological and
      pathophysiological conditions to facilitate protection and regeneration of
      tissues. Adenosine acts via specific GPCRs to either stimulate cyclic AMP
      formation, as exemplified by Gs -protein-coupled adenosine receptors (A2A and A2B
      ), or inhibit AC activity, in the case of Gi/o -coupled adenosine receptors (A1
      and A3 ). Recent advances in our understanding of GPCR structure have provided
      insights into the conformational changes that occur during receptor activation
      following binding of agonists to orthosteric (i.e. at the same binding site as an
      endogenous modulator) and allosteric regulators to allosteric sites (i.e. at a
      site that is topographically distinct from the endogenous modulator). Binding of
      drugs to allosteric sites may lead to changes in affinity or efficacy, and
      affords considerable potential for increased selectivity in new drug development.
      Herein, we provide an overview of the properties of selective allosteric
      regulators of the adenosine A1 and A3 receptors, focusing on the impact of
      receptor dimerization, mechanistic approaches to single-cell ligand-binding
      kinetics and the effects of A1 - and A3 -receptor allosteric modulators on in
      vivo pharmacology.

PMID- 24024787
TI  - Biocontrol of gray mold disease on strawberry fruit by integration of
      Lactobacillus plantarum A7 with ajwain and cinnamon essential oils.
AB  - This study was conducted to evaluate the efficacy of the Lactobacillus plantarum
      A7 (L. Plantarum), ajwain and cinnamon essential oils (AO and CO, respectively)
      in suppressing gray mold rot in strawberry fruit. AO and CO showed over 90%
      inhibition of radial mycelia growth with lower concentration of the oils per
      plate for all tested pathogens. Combined application of L. plantarum with AO and
      CO was tested to assess the possible synergistic effects of these 3 elements on
      the control of tested plant pathogens. In this case both combinations of L.
      plantarum + AO and L. plantarum + CO inhibited the mycelia growth of the
      pathogens completely. Results showed that the combined treatment of strawberry
      fruits with L. plantarum + AO (50 MUL) and L. plantarum + CO (100 MUL) resulted
      in remarkably improved control of Botrytis infections, in comparison with
      application of L. plantarum or essential oils alone. Quality attributes (that is
      pH, acidity, vitamin C, and total soluble solid) of the strawberry fruits did not
      change significantly (P < 0.01) when combination of Lactobacillus and essential
      oils was used. To the best of our knowledge, this is the first report on the
      effects of combination of a Lactobacillus as an antagonist bacterium with
      essential oils to increase the shelf life of strawberry. 

PMID- 24024788
TI  - The clinical potential of temsirolimus in second or later lines of treatment for
      metastatic renal cell carcinoma.
AB  - An impressive variety of targeted therapies has been approved for the treatment
      of metastatic renal cell carcinoma (mRCC). Despite promising progress, there are
      still unmet clinical needs. The optimal sequence of these agents in the
      therapeutic setting has not yet been determined. Most available data address
      first- and second-line therapy of clear cell RCC. The mTOR inhibitor temsirolimus
      has been approved for first-line treatment of mRCC, and there are new data
      addressing the use of temsirolimus in later therapeutic lines. Temsirolimus has
      discerning features compared with other currently registered drugs, such as its
      intravenous administration route-providing predictable bioavailability and
      adherence to treatment-and potential benefit in nonclear cell histologies. Here,
      we review the available literature on temsirolimus, with reference to data also
      available for everolimus, to determine its clinical potential in mRCC. 

PMID- 24024789
TI  - How to diagnose amyloidosis.
AB  - Amyloidosis is a rare but devastating condition caused by deposition of misfolded
      proteins as aggregates in the extracellular tissues of the body, leading to
      impairment of organ function. High clinical suspicion is required to facilitate
      early diagnosis. Correct identification of the causal amyloid protein is
      absolutely crucial for clinical management in order to avoid misdiagnosis and
      inappropriate, potentially harmful treatment, to assess prognosis, and to offer
      genetic counselling if relevant. This review summarises the current evidence on
      which the diagnosis and subtyping of amyloidosis is based, outlines the
      limitations of various diagnostic techniques, particularly in an Australian and
      New Zealand context, and discusses optimal strategies for the diagnostic approach
      to these patients. Recommendations are provided for when particularly to suspect
      amyloidosis, what investigations are required, as well as an approach to accurate
      subtyping of amyloidosis. 

PMID- 24024791
TI  - Visible light photoredox catalysis: synthesis of indazolo[2,3-a]quinolines from 2
      (2-nitrophenyl)-1,2,3,4-tetrahydroquinolines.
AB  - The synthesis of indazolo[2,3-a]quinoline derivatives in moderate to good yields
      from 2-(2-nitrophenyl)-1,2,3,4-tetrahydroquinolines via visible light photoredox
      catalysis is reported. The reaction involves a novel ruthenium-catalyzed
      intramolecular formation of the N-N bond of the indazole ring. 

PMID- 24024790
TI  - Restoration of angiogenic capacity of diabetes-insulted mesenchymal stem cells by
      oxytocin.
AB  - BACKGROUND: Angiogenesis is the main therapeutic mechanism of cell therapy for
      cardiovascular diseases, but diabetes is reported to reduce the function and
      number of progenitor cells. Therefore, we studied the effect of streptozotocin
      induced diabetes on the bone marrow-mesenchymal stem cell (MSC) function, and
      examined whether diabetes-impaired MSC could be rescued by pretreatment with
      oxytocin. RESULTS: MSCs were isolated and cultured from diabetic (DM) or non
      diabetic (non-DM) rat, and proliferation rate was compared. DM-MSC was pretreated
      with oxytocin and compared with non-DM-MSC. Angiogenic capacity was estimated by
      tube formation and Matrigel plug assay, and therapeutic efficacy was studied in
      rat myocardial infarction (MI) model.The proliferation and angiogenic activity of
      DM-MSC were severely impaired but significantly improved by pretreatment with
      oxytocin. Kruppel-like factor 2 (KLF2), a critical angiogenic factor, was
      dramatically reduced in DM-MSC and significantly restored by oxytocin. In the
      Matrigel plug assay, vessel formation of DM-BMSCs was attenuated but was
      recovered by oxytocin. In rat MI model, DM-MSC injection did not ameliorate
      cardiac injury, whereas oxytocin-pretreated DM-MSC improved cardiac function and
      reduced fibrosis. CONCLUSIONS: Our results show that diabetes influenced MSC by
      reducing angiogenic capacity and therapeutic potential. We demonstrate the
      striking effect of oxytocin on stem cell dysfunction and suggest the use of
      oxytocin as a priming reagent in autologous stem cell therapy.

PMID- 24024792
TI  - Asthma care practicing among general practitioners in Lebanon: a cross-sectional
      study.
AB  - OBJECTIVES: The aim of this study was to characterize the current practice of
      asthma among general practitioners (GPs) in Lebanon. METHODS: Out of 2450
      Lebanese registered GPs, a representative sample of 330 were stratified by region
      to fill out the questionnaire constructed on the basis of surveys developed
      mainly by the Chicago Asthma Surveillance Initiative Report Team in newly
      moderate persistent asthma patients aged 5 years and above. The questionnaire
      included information about ascertaining diagnostic techniques,
      pharmacotherapeutic approaches, formal patient education program; asthma related
      continuing medical education and asthma practice guidelines. RESULTS: Totally,
      302 completed the questionnaire achieving a response rate of 91.5%. Chest
      radiography was the most commonly used diagnostic test (98%), while stain for
      eosinophilia was the less commonly used (7.9%). For clinical monitoring, cough
      and wheezing (98.7%) were mostly assessed. Short acting inhaled beta2-agonists
      were often the most prescribed (94.3%) followed by inhaled corticosteroids
      (87.4%) then by long acting beta-agonist (LABA) and theophylline (27.5% and
      20.9%, respectively). Moreover, 10% of GPs provided formal asthma education
      program, 72.2% attended professional education and 65% adopted guidelines.
      CONCLUSION: Based on current international guidelines, the overall Lebanese GPs
      practice of asthma management is not at an acceptable standard. Therefore, it is
      recommended to improve monitoring parameters, implement the asthma guidelines
      nationally and improve patient education.

PMID- 24024793
TI  - Physiological acclimation to drought stress in Solidago canadensis.
AB  - Solidago canadensis is an invasive species from North America that is spreading
      across Europe, Australia and temperate Asia. We hypothesized that the species'
      wide ecological amplitude is also based on its potential in hydraulic
      acclimation, and analyzed hydraulic and anatomical properties along a transect
      with decreasing soil humidity. Stem hydraulic conductivity, vulnerability to
      drought-induced embolism, stomatal closure during dehydration and xylem
      anatomical parameters were quantified at three sites. At the humid site, specific
      hydraulic conductivity of stems (1.0 +/- 0.2 kg m(-1)  MPa(-1)  s(-1)) was about
      twofold higher, and leaf-specific conductivity about 1.5 times higher (3.1 +/-
      0.5 kg m(-1)  MPa(-1)  s(-1)) than at the dry site. Water potential (Psi) at 50%
      loss of conductivity was -3.7 +/- 0.1 MPa at the dry site and -3.1 +/- 0.2 MPa at
      the humid site (September). Vulnerability to drought-induced embolism decreased
      along the transect and over the vegetation period. At drier sites, stomata
      started closing at lower Psi while complete stomatal closure was reached at less
      negative Psi (12% of maximum stomatal conductance: -2.5 +/- 0.0 and -3.0 +/- 0.2
      MPa at the dry and humid site). The safety margin between stomatal closure and
      50% loss of conductivity was 1.2 and 0.2 MPa at the dry and humid sites. The
      observed variability indicated an efficient acclimation in hydraulic conductivity
      and safety: plants at dry sites exhibited lower specific hydraulic conductivity,
      higher embolism resistance and broader safety margins, signifying a trade-off
      between the hydraulic safety and efficiency. The observed intraspecific
      plasticity in hydraulic and anatomical traits may help to explain the invasive
      potential of this species.

PMID- 24024794
TI  - A role for peripheral 5-HT2 receptors in serotonin-induced facilitation of the
      expulsion phase of ejaculation in male rats.
AB  - INTRODUCTION: The urethrogenital reflex (UGR) is used as a physiological animal
      model of the autonomic and somatic activity that accompanies ejaculatory-like
      reflexes (ELRs). Serotonin (5-HT) plays an important role in regulating
      ejaculation. AIM: To examine the effects of intraurethral 5-HT on ELRs and to
      examine the effects of various 5-HT receptor subtypes on the 5-HT-induced changes
      in the ELRs. METHODS: The effects of intraurethral infusion of 5-HT on ELRs were
      examined by monitoring the urethrogenital reflex in male rats. The effects of
      various 5-HT receptor-specific antagonists on the 5-HT-induced responses were
      examined. MAIN OUTCOME MEASURES: Main outcome measures were urethral pressure
      threshold required to elicit the UGR and bulbospongiosus activity or ELRs.
      RESULTS: Intraurethral infusion of 5-HT (10-1,000 MUM) produced a dose-dependent
      facilitation of the UGR, i.e., decrease in threshold urethral perfusion pressure
      and an increase in number of ELRs. The 5-HT3 receptor antagonists tropisetron (1
      and 3 mg/kg, i.v.) and ramosetron (0.1 and 1 mg/kg, i.v.), the 5-HT7 receptor
      antagonist SB269970 (3 mg/kg, i.v.), and the 5-HT1 A receptor antagonist WAY
      100635 (1 mg/kg, i.v.) all failed to inhibit 5-HT-induced facilitation of the
      UGR. However, ritanserin (1 mg/kg, i.v.), a nonselective 5-HT2 receptor
      antagonist, and xylamidine (0.01-1 mg/kg, i.v.), a peripherally restricted
      nonselective 5-HT2 receptor antagonist, significantly inhibited both the decrease
      in urethral pressure threshold and the increase in number of ELRs induced by
      intraurethral infusion of 5-HT. CONCLUSION: These results suggest that in the
      male rat urethra, peripheral 5-HT2 receptors are involved in the 5-HT-induced
      facilitation of the expulsion phase of ejaculation.

PMID- 24024795
TI  - Critically appraising prenatal genetic diagnosis to prevent disorders of sexual
      development: an opportunity missed.

PMID- 24024797
TI  - Athletes are Guinea pigs.

PMID- 24024796
TI  - Sports medicine and ethics.
AB  - Physicians working in the world of competitive sports face unique ethical
      challenges, many of which center around conflicts of interest. Team-employed
      physicians have obligations to act in the club's best interest while caring for
      the individual athlete. As such, they must balance issues like protecting versus
      sharing health information, as well as issues regarding autonomous informed
      consent versus paternalistic decision making in determining whether an athlete
      may compete safely. Moreover, the physician has to deal with an athlete's
      decisions about performance enhancement and return to play, pursuit of which may
      not be in the athlete's long-term best interests but may benefit the athlete and
      team in the short term. These difficult tasks are complicated by the lack of
      evidence-based standards in a field influenced by the lure of financial gains for
      multiple parties involved. In this article, we review ethical issues in sports
      medicine with specific attention paid to American professional football. 

PMID- 24024798
TI  - Concussion in sports medicine ethics: policy, epistemic and ethical problems.

PMID- 24024799
TI  - From sports ethics to labor relations.

PMID- 24024800
TI  - If you can't walk the walk, do you have to talk the talk: ethical considerations
      for the emerging field of sports genomics.

PMID- 24024801
TI  - Prescription for "sports medicine and ethics".

PMID- 24024802
TI  - Professional codes of ethics as leading benchmarks?

PMID- 24024803
TI  - Do conflicts of interest create a new professional norm? Physical therapists and
      workers' compensation.

PMID- 24024804
TI  - Gender eugenics? The ethics of PGD for intersex conditions.
AB  - This article discusses the ethics of the use of preimplantation genetic diagnosis
      (PGD) to prevent the birth of children with intersex conditions/disorders of sex
      development (DSDs), such as congenital adrenal hyperplasia (CAH) and androgen
      insensitivity syndrome (AIS). While pediatric surgeries performed on children
      with ambiguous genitalia have been the topic of intense bioethical controversy,
      there has been almost no discussion to date of the ethics of the use of PGD to
      reduce the prevalence of these conditions. I suggest that PGD for those
      conditions that involve serious medical risks for those born with them is morally
      permissible and that PGD for other "cosmetic" variations in sexual anatomy is
      more defensible than might first appear. However, importantly, the arguments that
      establish the latter claim have radical and disturbing implications for our
      attitude toward diversity more generally. 

PMID- 24024805
TI  - Queer liberation, not elimination: why selecting against intersex is not
      "straight" forward.

PMID- 24024806
TI  - PGD and parental obligations: what parents owe to communities that do not yet
      exist.

PMID- 24024808
TI  - The limits of procreative liberty.

PMID- 24024807
TI  - On the inseparability of gender eugenics, ethics, and public policy: an Israeli
      perspective.

PMID- 24024809
TI  - Informed choice and PGD to prevent "intersex conditions".

PMID- 24024810
TI  - Preimplantation genetic diagnosis for intersex conditions: beyond parental
      decision making.

PMID- 24024811
TI  - The social costs of preempting intersex traits.

PMID- 24024812
TI  - The ethics of PGD for intersex conditions: problems with the diversity argument.

PMID- 24024813
TI  - For the sake of "normality"? Medical indication, social justification, and the
      welfare of children.

PMID- 24024814
TI  - Gender eugenics between medicine, culture, and society.

PMID- 24024815
TI  - Challenging cases in research ethics.

PMID- 24024816
TI  - The ethics of contacting family members of a subject in a genetic research study
      to return results for an autosomal dominant syndrome.
AB  - This case explores the ethical landscape around recontacting a subject's
      relatives to return genetic research results when the informed consent form
      signed by the original cohort of subjects is silent on whether investigators may
      share new information with the research subject's family. As a result of rapid
      advances in genetic technology, methods to identify genetic markers can mature
      during the life course of a study. In this case, the investigators identified the
      genetic mutation responsible for the disorder after a number of their original
      subjects had died. The researchers now have the ability to inform relatives of
      the subject about their risk of developing the same disease. Mark Rothstein, JD,
      from the University of Louisville School of Medicine, provides an overview of the
      medical/scientific, legal, and ethical issues underlying this case. Lauren
      Milner, PhD, and colleagues at Stanford University explore how the relationship
      between researcher and subject affect this debate. Seema Shah, JD, and colleagues
      at the National Institutes of Health and University of California, Los Angeles
      (UCLA) discuss whether and how requirements of the duty to warn are applicable in
      this case. 

PMID- 24024817
TI  - What does the duty to warn require?

PMID- 24024818
TI  - Should researchers disclose results to descendants?

PMID- 24024819
TI  - Relationships matter: ethical considerations for returning results to family
      members of deceased subjects.

PMID- 24024820
TI  - Managing disclosure of research misconduct by a graduate student to a university
      mental health professional during a clinical counseling session.
AB  - This case looks at the question of how to consider obligations of confidentiality
      by a mental health professional who works for an institution and learns that a
      student has been using a drug intended for an animal research project. Dr. Paul
      Appelbaum, MD, a psychiatrist at Columbia University, examines the issue of the
      limits of confidentiality. Nicholas Steneck, PhD, a scholar in research
      misconduct at the University of Michigan, explores the obligations to report
      research misconduct. Walter Limehouse, MD, an ethicist at the Medical University
      of South Carolina, considers the systems issues raised by this case and offers
      some suggestions that might change the institutional environment. 

PMID- 24024821
TI  - A systems-level approach to resolve tension between research misconduct and
      confidentiality.

PMID- 24024822
TI  - Let therapists be therapists, not police.

PMID- 24024823
TI  - Why misconduct trumps patient-therapist confidentiality and ways to avoid the
      disclosure dilemma.

PMID- 24024825
TI  - Postoperative pain after major abdominal surgery: is it gender related? An
      observational prospective study.
AB  - OBJECTIVES: Gender may be associated with postoperative pain. This study aimed to
      assess pain intensity and postoperative analgesic requirements in female and male
      patients scheduled for major abdominal surgery. METHODS: Sixty-five patients, 31
      men and 34 women, scheduled for major abdominal surgery were recruited.
      Anesthesia and intraoperative analgesics were standardized in all patients.
      Postoperatively, all patients had access to a 60 mL PCA pump containing 1 mg/mL
      morphine and 50 MUg/mL droperidol. Morphine consumption and VAS scores at rest
      and after cough were recorded 2, 4, 8, 24, and 48 hours postoperatively. RESULTS:
      Of the 65 patients recruited for the study, 30 women and 30 men aged 65 +/- 8.9
      and 66 +/- 9.0 years, respectively, were included in the analysis. Morphine
      consumption was examined 2, 4, 8, 24, and 48 hours after surgery and did not
      differ in women vs. men (mean +/- standard deviation, 4.4 +/- 3.2 vs. 5 +/- 4.8,
      7.2 +/- 4.8 vs. 8.7 +/- 6.9, 10.4 +/- 7.1, vs. 12.5 +/- 8.5, 22.9 +/- 11.6 vs.
      25.6 +/- 14.5, and 36.2 +/- 15.7 vs. 39.7 +/- 21.7 mg, P = 0.384). Cumulative
      morphine consumption was not significantly different in women vs. men when
      normalized for body mass index (mean +/- standard deviation, 0.17 +/- 0.13, 0.28
      +/- 0.20, 0.40 +/- 0.30, 0.88 +/- 0.46, and 1.38 +/- 0.59 mg/kg(/) m(2) in women
      and 0.18 +/- 0.18, 0.31 +/- 0.25, 0.46 +/- 0.32, 0.95 +/- 0.54, and 1.47 +/- 0.81
      mg/kg/m(2) in men at 2, 4, 8, 24, and 48 hours postoperatively (P = 0.567). Both
      genders exhibited similar VAS pain scores (mm) at rest and after cough (P =
      0.476, P = 0.378, respectively). CONCLUSIONS: Postoperative morphine requirements
      did not differ between female and male patients undergoing major abdominal
      surgery. Pain intensity reported at rest and after cough did not differ between
      the 2 groups.

PMID- 24024826
TI  - U-CARE: Internet-based stepped care with interactive support and cognitive
      behavioral therapy for reduction of anxiety and depressive symptoms in cancer--a
      clinical trial protocol.
AB  - BACKGROUND: Approximately 20-30% of patients with cancer experience a clinically
      relevant level of emotional distress in response to disease and treatment. This
      in itself is alarming but it is even more problematic because it is often
      difficult for physicians and nurses to identify cancer patients who experience
      clinically relevant levels of anxiety and depression symptoms. This can result in
      persistent distress and can cause human suffering as well as costs for
      individuals and to the community. METHODS: Applying a multi-disciplinary and
      design-oriented approach aimed at attaining new evidence-based knowledge in basic
      and applied psychosocial oncology, this protocol will evaluate an intervention to
      be implemented in clinical practice to reduce cancer patient anxiety and
      depression. A prospective randomized design will be used.The overarching goal of
      the intervention is to promote psychosocial health among patients suffering from
      cancer by means of self-help programmes delivered via an Internet platform.
      Another goal is to reduce costs for individuals and society, caused by emotional
      distress in response to cancer.Following screening to detect levels of patient
      distress, patients will be randomized to standard care or a stepped care
      intervention. For patients randomized to the intervention, step 1 will consist of
      self-help material, a chat forum where participants will be able to communicate
      with each other, and a Frequently Asked Questions (FAQ) section where they can
      ask questions and get answers from an expert. Patients in the intervention group
      who still report symptoms of anxiety or depression after access to step 1 will be
      offered step 2, which will consist of cognitive behavioral therapy (CBT)
      administered by a personal therapist. The primary end point of the study is
      patients' levels of anxiety and depression, evaluated longitudinally during and
      after the intervention. DISCUSSION: There is a lack of controlled studies of the
      psychological and behavioral processes involved in this type of intervention for
      anxiety and depressive disorders. Since anxiety and depressive symptoms are
      relatively common in patients with cancer and the availability of adequate
      support efforts is limited, there is a need to develop evidence-based stepped
      care for patients with cancer, to be delivered via the Internet. TRIAL
      REGISTRATION: ClinicalTrials.gov Identifier: NCT01630681.

PMID- 24024828
TI  - Journal of Internal Medicine - 150 years of medical development.

PMID- 24024829
TI  - Disinfection of ballast water with iron activated persulfate.
AB  - The treatment of ballast water carried onboard ships is critical to reduce the
      spread of nonindigenous aquatic organisms that potentially include noxious and
      harmful taxa. We tested the efficacy of persulfate (peroxydisulfate, S2O8(2-),
      PS) activated with zerovalent iron (Fe(0)) as a chemical biocide against two taxa
      of marine phytoplankton grown in bench-scale, batch cultures: the diatom,
      Pseudonitzshia delicatissima and the green alga, Dunaliella tertiolecta . After
      testing a range of PS concentrations (0-4 mM activated PS) and exposure times (1
      7 days), we determined that a dosage of 4 mM of activated PS was required to
      inactivate cells from both species, as indicated by reduced or halted growth and
      a reduction in photosynthetic performance. Longer exposure times were required to
      fully inactivate D. tertiolecta (7 days) compared to P. delicatissima (5 days).
      Under these conditions, no recovery was observed upon placing cells from the
      exposed cultures into fresh media lacking biocide. The results demonstrate that
      activated PS is an effective chemical biocide against species of marine
      phytoplankton. The lack of harmful byproducts produced during application makes
      PS an attractive alternative to other biocides currently in use for ballast water
      treatments and merits further testing at a larger scale. 

PMID- 24024827
TI  - A Gro/TLE-NuRD corepressor complex facilitates Tbx20-dependent transcriptional
      repression.
AB  - The cardiac transcription factor Tbx20 has a critical role in the proper
      morphogenetic development of the vertebrate heart, and its misregulation has been
      implicated in human congenital heart disease. Although it is established that
      Tbx20 exerts its function in the embryonic heart through positive and negative
      regulation of distinct gene programs, it is unclear how Tbx20 mediates proper
      transcriptional regulation of its target genes. Here, using a combinatorial
      proteomic and bioinformatic approach, we present the first characterization of
      Tbx20 transcriptional protein complexes. We have systematically investigated
      Tbx20 protein-protein interactions by immunoaffinity purification of tagged Tbx20
      followed by proteomic analysis using GeLC-MS/MS, gene ontology classification,
      and functional network analysis. We demonstrate that Tbx20 is associated with a
      chromatin remodeling network composed of TLE/Groucho corepressors, members of the
      Nucleosome Remodeling and Deacetylase (NuRD) complex, the chromatin remodeling
      ATPases RUVBL1/RUVBL2, and the T-box repressor Tbx18. We determined that the
      interaction with TLE corepressors is mediated via an eh1 binding motif in Tbx20.
      Moreover, we demonstrated that ablation of this motif results in a failure to
      properly assemble the repression network and disrupts Tbx20 function in vivo.
      Importantly, we validated Tbx20-TLE interactions in the mouse embryonic heart,
      and identified developmental genes regulated by Tbx20-TLE binding, thereby
      confirming a primary role for a Tbx20-TLE repressor complex in embryonic heart
      development. Together, these studies suggest a model in which Tbx20 associates
      with a Gro/TLE-NuRD repressor complex to prevent inappropriate gene activation
      within the forming heart. 

PMID- 24024830
TI  - Coupled effects of substrate adhesion and intermolecular forces on polymer thin
      film glass-transition behavior.
AB  - Intermolecular noncovalent forces between polymer chains influence the mobility
      and glass-transition temperature (Tg), where weaker interchain interactions, all
      else being the same, typically results in lower bulk polymer Tg. Using molecular
      dynamics simulations, here we show that this relation can become invalid for
      supported ultrathin films when the substrate-polymer interaction is extremely
      strong and the polymer-polymer interactions are much weaker. This contrasting
      trend is found to be due to a more pronounced substrate-induced appreciation of
      the film Tg for polymers with weaker intermolecular interactions and low bulk Tg.
      We show that optimizing this coupling between substrate adhesion and bulk Tg
      maximizes thin film Tg, paving the way for tuning film properties through
      interface nanoengineering. 

PMID- 24024831
TI  - The significance of intraocular pressure elevation during sleep-related postures.
AB  - Intraocular pressure and its fluctuations are associated with the development and
      progression of glaucoma. This review examines the potential for sleep-related
      intraocular pressure elevations to contribute to the onset and progression of
      glaucoma. Also considered is the potential for patient education and appropriate
      changes in behaviour as a means of reducing exposure to elevated intraocular
      pressure. A PubMed search using the combination key words 'glaucoma and sleep'
      was conducted. Information was taken from representative articles from the 187
      yielded from the search. Additional papers were found after accessing references
      in selected papers. Several studies have indicated an association between the
      progression of glaucoma and both lateral decubitus (side sleep) and supine sleep
      positions. Evidence that prone sleep positions could raise intraocular pressure
      to high levels suggests a similar if not stronger association. Intraocular
      pressure elevation and progression of glaucoma associated with sleep positions
      suggest that there are similar risks of progression associated with sleep-related
      body postures adopted during non-sleep activities, such as reading, watching
      television and sun-bathing. Posture-related management of patients with glaucoma,
      which is intended to reduce the risk or degree of progression may include the use
      of specially designed pillows, bed-head elevation and recommendations to avoid
      postures which induce higher intraocular pressure. 

PMID- 24024832
TI  - Bilateral globus pallidus stimulation in Westphal variant of huntington disease.

PMID- 24024833
TI  - Vanadium bisimide bonding investigated by X-ray crystallography, 51V and 13C
      nuclear magnetic resonance spectroscopy, and V L(3,2)-edge X-ray absorption near
      edge structure spectroscopy.
AB  - Syntheses of neutral halide and aryl vanadium bisimides are described. Treatment
      of VCl2(NtBu)[NTMS(N(t)Bu)], 2, with PMe3, PEt3, PMe2Ph, or pyridine gave
      vanadium bisimides via TMSCl elimination in good yield: VCl(PMe3)2(N(t)Bu)2 3,
      VCl(PEt3)2(N(t)Bu)2 4, VCl(PMe2Ph)2(N(t)Bu)2 5, and VCl(Py)2(N(t)Bu)2 6. The
      halide series (Cl-I) was synthesized by use of TMSBr and TMSI to give
      VBr(PMe3)2(N(t)Bu)2 7 and VI(PMe3)2(N(t)Bu)2 8. The phenyl derivative was
      obtained by reaction of 3 with MgPh2 to give VPh(PMe3)2(N(t)Bu)2 9. These neutral
      complexes are compared to the previously reported cationic bisimides
      [V(PMe3)3(N(t)Bu)2][Al(PFTB)4] 10, [V(PEt3)2(N(t)Bu)2][Al(PFTB)4] 11, and
      [V(DMAP)(PEt3)2(N(t)Bu)2][Al(PFTB)4] 12 (DMAP = dimethylaminopyridine, PFTB =
      perfluoro-tert-butoxide). Characterization of the complexes by X-ray diffraction,
      (13)C NMR, (51)V NMR, and V L(3,2)-edge X-ray absorption near-edge structure
      (XANES) spectroscopy provides a description of the electronic structure in
      comparison to group 6 bisimides and the bent metallocene analogues. The
      electronic structure is dominated by pi bonding to the imides, and localization
      of electron density at the nitrogen atoms of the imides is dictated by the cone
      angle and donating ability of the axial neutral supporting ligands. This
      phenomenon is clearly seen in the sensitivity of (51)V NMR shift, (13)C NMR
      Deltadelta(alphabeta), and L3-edge energy to the nature of the supporting
      phosphine ligand, which defines the parameters for designing cationic group 5
      bisimides that would be capable of breaking stronger sigma bonds. Conversely, all
      three methods show little dependence on the variable equatorial halide ligand.
      Furthermore, this analysis allows for quantification of the electronic
      differences between vanadium bisimides and the structurally analogous mixed
      Cp/imide system CpV(N(t)Bu)X2 (Cp = C5H5(1-)).

PMID- 24024834
TI  - Review article: coffee consumption, the metabolic syndrome and non-alcoholic
      fatty liver disease.
AB  - BACKGROUND: Coffee consumption may modulate the risk of the metabolic syndrome
      (MetS) and non-alcoholic fatty liver disease (NAFLD). AIM: To review the
      experimental, epidemiological and clinical studies investigating the association
      between coffee consumption and the risk of MetS and NAFLD. METHODS: A literature
      search was conducted with the aim of finding original experimental,
      epidemiological and clinical articles on the association between coffee
      consumption, MetS and NAFLD. The following databases were used: PubMed, Embase,
      Scopus and Science Direct. We included articles written in English and published
      up to July 2013. RESULTS: Three experimental animal studies investigated the
      effects of coffee in the MetS, whereas five examined whether experimental coffee
      intake may modulate the risk of fatty liver infiltration. All of the animal
      studies showed a protective effect of coffee towards the development of MetS and
      NAFLD. Moreover, we identified eleven epidemiological and clinical studies that
      met the inclusion criteria. Of them, six were carried out on the risk of the MetS
      and five on the risk of NAFLD. Four of the six studies reported an inverse
      association between coffee consumption and the risk of MetS. The two studies
      showing negative results were from the same study cohort consisting of young
      persons with a low prevalence of the MetS. All of the epidemiological and
      clinical studies on NAFLD reported a protective effect of coffee intake.
      CONCLUSIONS: Coffee intake can reduce the risk of NAFLD. Whether this effect may
      be mediated by certain components of the MetS deserves further investigation.

PMID- 24024835
TI  - Transforming academic health centers for an uncertain future.

PMID- 24024836
TI  - Balancing AMCs' missions and health care costs--mission impossible?

PMID- 24024837
TI  - Signal in the noise.

PMID- 24024840
TI  - Therapy for hepatitis C virus-related cryoglobulinemic vasculitis.

PMID- 24024838
TI  - Gonadal steroids and body composition, strength, and sexual function in men.
AB  - BACKGROUND: Current approaches to diagnosing testosterone deficiency do not
      consider the physiological consequences of various testosterone levels or whether
      deficiencies of testosterone, estradiol, or both account for clinical
      manifestations. METHODS: We provided 198 healthy men 20 to 50 years of age with
      goserelin acetate (to suppress endogenous testosterone and estradiol) and
      randomly assigned them to receive a placebo gel or 1.25 g, 2.5 g, 5 g, or 10 g of
      testosterone gel daily for 16 weeks. Another 202 healthy men received goserelin
      acetate, placebo gel or testosterone gel, and anastrozole (to suppress the
      conversion of testosterone to estradiol). Changes in the percentage of body fat
      and in lean mass were the primary outcomes. Subcutaneous- and intraabdominal-fat
      areas, thigh-muscle area and strength, and sexual function were also assessed.
      RESULTS: The percentage of body fat increased in groups receiving placebo or 1.25
      g or 2.5 g of testosterone daily without anastrozole (mean testosterone level,
      44+/-13 ng per deciliter, 191+/-78 ng per deciliter, and 337+/-173 ng per
      deciliter, respectively). Lean mass and thigh-muscle area decreased in men
      receiving placebo and in those receiving 1.25 g of testosterone daily without
      anastrozole. Leg-press strength fell only with placebo administration. In
      general, sexual desire declined as the testosterone dose was reduced.
      CONCLUSIONS: The amount of testosterone required to maintain lean mass, fat mass,
      strength, and sexual function varied widely in men. Androgen deficiency accounted
      for decreases in lean mass, muscle size, and strength; estrogen deficiency
      primarily accounted for increases in body fat; and both contributed to the
      decline in sexual function. Our findings support changes in the approach to
      evaluation and management of hypogonadism in men. (Funded by the National
      Institutes of Health and others; ClinicalTrials.gov number, NCT00114114.).

PMID- 24024839
TI  - Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer.
AB  - BACKGROUND: Patients with metastatic colorectal cancer that harbors KRAS
      mutations in exon 2 do not benefit from anti-epidermal growth factor receptor
      (EGFR) therapy. Other activating RAS mutations may also be negative predictive
      biomarkers for anti-EGFR therapy. METHODS: In this prospective-retrospective
      analysis, we assessed the efficacy and safety of panitumumab plus oxaliplatin,
      fluorouracil, and leucovorin (FOLFOX4) as compared with FOLFOX4 alone, according
      to RAS (KRAS or NRAS) or BRAF mutation status. A total of 639 patients who had
      metastatic colorectal cancer without KRAS mutations in exon 2 had results for at
      least one of the following: KRAS exon 3 or 4; NRAS exon 2, 3, or 4; or BRAF exon
      15. The overall rate of ascertainment of RAS status was 90%. RESULTS: Among 512
      patients without RAS mutations, progression-free survival was 10.1 months with
      panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone (hazard ratio for
      progression or death with combination therapy, 0.72; 95% confidence interval
      [CI], 0.58 to 0.90; P=0.004). Overall survival was 26.0 months in the panitumumab
      FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group (hazard ratio for
      death, 0.78; 95% CI, 0.62 to 0.99; P=0.04). A total of 108 patients (17%) with
      nonmutated KRAS exon 2 had other RAS mutations. These mutations were associated
      with inferior progression-free survival and overall survival with panitumumab
      FOLFOX4 treatment, which was consistent with the findings in patients with KRAS
      mutations in exon 2. BRAF mutations were a negative prognostic factor. No new
      safety signals were identified. CONCLUSIONS: Additional RAS mutations predicted a
      lack of response in patients who received panitumumab-FOLFOX4. In patients who
      had metastatic colorectal cancer without RAS mutations, improvements in overall
      survival were observed with panitumumab-FOLFOX4 therapy. (Funded by Amgen and
      others; PRIME ClinicalTrials.gov number, NCT00364013.).

PMID- 24024841
TI  - Images in clinical medicine. Hyperectasis of the tympanic membrane.

PMID- 24024842
TI  - Case records of the Massachusetts General Hospital. Case 28-2013. A 52-year-old
      man with cardiac arrest after an acute myocardial infarction.

PMID- 24024843
TI  - Mechanisms of action of testosterone--unraveling a Gordian knot.

PMID- 24024844
TI  - Beyond exon 2--the developing story of RAS mutations in colorectal cancer.

PMID- 24024845
TI  - Randomized clinical trials--removing unnecessary obstacles.

PMID- 24024846
TI  - The public and the conflict over future Medicare spending.

PMID- 24024847
TI  - Nighttime physician staffing in an intensive care unit.

PMID- 24024848
TI  - Nighttime physician staffing in an intensive care unit.

PMID- 24024849
TI  - Nighttime physician staffing in an intensive care unit.

PMID- 24024850
TI  - Nighttime physician staffing in an intensive care unit.

PMID- 24024851
TI  - Inhaled adrenaline in acute bronchiolitis.

PMID- 24024852
TI  - Inhaled adrenaline in acute bronchiolitis.

PMID- 24024853
TI  - Inhaled adrenaline in acute bronchiolitis.

PMID- 24024854
TI  - Antithrombotic therapy and invasive procedures.

PMID- 24024855
TI  - Antithrombotic therapy and invasive procedures.

PMID- 24024856
TI  - Antithrombotic therapy and invasive procedures.

PMID- 24024857
TI  - Antithrombotic therapy and invasive procedures.

PMID- 24024858
TI  - Antithrombotic therapy and invasive procedures.

PMID- 24024859
TI  - Antithrombotic therapy and invasive procedures.

PMID- 24024860
TI  - Case reports of PML in patients treated for psoriasis.

PMID- 24024861
TI  - Case reports of PML in patients treated for psoriasis.

PMID- 24024862
TI  - Case reports of PML in patients treated for psoriasis.

PMID- 24024863
TI  - Videos in clinical medicine. How to perform a punch biopsy of the skin.

PMID- 24024864
TI  - Images in clinical medicine. Grynfeltt hernia.

PMID- 24024865
TI  - Clinical decisions. Physician-assisted suicide--polling results.

PMID- 24024866
TI  - Simulations of hot-core chemistry.

PMID- 24024867
TI  - Towards a better cannabis drug.
AB  - This commentary discusses the importance of a new study entitled 'Cannabidiol
      attenuates deficits of visuo-spatial associative memory induced by Delta(9) 
      tetrahydrocannabinol' by Wright et al. from the Scripps Institute in La Jolla,
      California. The results in this study show that the non-psychoactive cannabis
      constituent cannabidiol opposes some, but not all, forms of behavioural and
      memory disruption caused by Delta(9) -tetrahydrocannabinol in male rhesus
      monkeys. LINKED ARTICLE: This article is a commentary on the research paper by
      Wright et al., pp 1365-1373 of this issue. To view this paper visit
      http://dx.doi.org/10.1111/bph.12199.

PMID- 24024868
TI  - Identification of fungi in fungal ball sinusitis: comparison between MUC5B
      immunohistochemical and Grocott methenamine silver staining.
AB  - CONCLUSION: MUC5B immunohistochemical staining was a valuable method for
      identifying fungi in fungal ball sinusitis, especially in distinguishing
      aspergillus and mucor. Combined infection with Aspergillus and Mucor fungi was
      the most common pattern in fungal ball sinusitis. OBJECTIVE: To assess the value
      of MUC5B immunohistochemical staining in identifying fungi in fungal ball
      sinusitis by comparing it with conventional Grocott methenamine silver (GMS)
      staining. METHODS: GMS staining and MUC5B immunohistochemical staining were used
      to identify fungi in mucopurulent cheesy or clay-like tissues from sinuses in 180
      fungal ball sinusitis patients, and the examination results were compared.
      RESULTS: In 180 samples of fungal ball sinusitis, GMS staining showed Aspergillus
      in 130, Mucor in 88, and Candida albicans in 6, while MUC5B immunohistochemical
      staining identified Aspergillus in 166, Mucor in 172, and Candida albicans in 16.
      The fungal detection rate for MUC5B immunohistochemical staining was markedly
      greater than that for GMS staining (p < 0.01). This implies that MUC5B
      immunohistochemical staining was more sensitive than GMS staining in identifying
      fungi in fungal ball sinusitis. Mixed infection of Aspergillus and Mucor was
      present in 146 of 180 patients (81.1%).

PMID- 24024869
TI  - Beneficial effects of high atorvastatin dose reloading prior to percutaneous
      coronary intervention.

PMID- 24024870
TI  - Spray-dried structured lipid containing long-chain polyunsaturated fatty acids
      for use in infant formulas.
AB  - Human milk fat (HMF) analogs are structured lipids (SLs) modified to have
      palmitic acid content at the sn-2 position of the triacylglycerol (TAG) and fatty
      acid composition comparable to HMF. Some of these SLs are also designed to
      incorporate long-chain polyunsaturated fatty acids (LCPUFAs) because of their
      important role in infant development. In this study, Maillard reaction products
      (MRPs), obtained from heated whey protein isolates and corn syrup solids (CSS)
      solution, were used as encapsulants for microencapsulation of 2 enzymatically
      synthesized SLs for infant formula applications. The encapsulated SL powders were
      obtained through spray-drying and evaluated in terms of their microencapsulation
      efficiency, chemical and physical properties, oxidative stability, and
      dispersibility. The microencapsulation efficiency of the SLs was 90%.
      Dispersibility test using particle size measurement demonstrated that these
      powders dispersed quickly into a homogeneous suspension. The encapsulated SL
      powders had low peroxide and thiobarbituric acid-reactive substances values.
      Lower oxidative stability was obtained in the powder containing SL with a higher
      degree of unsaturation and a lower concentration of tocopherols. The results
      demonstrated that the degree of fatty acid unsaturation and concentration of
      endogenous antioxidant in starting oils influenced the oxidative stability of the
      encapsulated SLs. 

PMID- 24024871
TI  - The evolving history of influenza viruses and influenza vaccines.
AB  - The isolation of influenza virus 80 years ago in 1933 very quickly led to the
      development of the first generation of live-attenuated vaccines. The first
      inactivated influenza vaccine was monovalent (influenza A). In 1942, a bivalent
      vaccine was produced after the discovery of influenza B. It was later discovered
      that influenza viruses mutated leading to antigenic changes. Since 1973, the WHO
      has issued annual recommendations for the composition of the influenza vaccine
      based on results from surveillance systems that identify currently circulating
      strains. In 1978, the first trivalent vaccine included two influenza A strains
      and one influenza B strain. Currently, there are two influenza B lineages
      circulating; in the latest WHO recommendations, it is suggested that a second B
      strain could be added to give a quadrivalent vaccine. The history of influenza
      vaccine and the associated technology shows how the vaccine has evolved to match
      the evolution of influenza viruses. 

PMID- 24024872
TI  - A novel role for antibiotic resistance plasmids in facilitating Salmonella
      adaptation to non-host environments.
AB  - It is believed that the main role of plasmids that encode multiple antibiotic
      resistance is to confer their hosts the ability to survive in the presence of
      antimicrobial compounds. In the pathogenic bacterium Salmonella, plasmids of the
      incompatibility group HI1 account for a significant proportion of antibiotic
      resistance phenotypes. In this work, we show that plasmid R27 has a strong impact
      on the global transcriptome of Salmonella Typhimurium strain SL1344 when cells
      grow at low temperature and enter the stationary phase. Down-regulated genes
      include pathogenicity islands, anaerobic respiration and metabolism determinants.
      Up-regulated genes include factors involved in the response to nutrient
      starvation, antimicrobial resistance, iron metabolism and the heat shock
      response. Accordingly, cells harbouring R27 are more resistant to heat shock than
      plasmid-free cells. The use of a different IncHI1 plasmid, pHCM1, provided
      evidence that these plasmids facilitate adaptation of Salmonella to environmental
      conditions outside their host(s). This is consistent with the fact that
      conjugative transfer of IncHI1 plasmids only occurs at low temperature. A
      significant number of the R27-dependent alterations in gene expression could be
      correlated with expression of a plasmid-encoded orthologue of the global
      modulator H-NS, which is up-regulated when cells grow at low temperature. 

PMID- 24024873
TI  - Ventriculoperitoneal shunt survival in children who require additional abdominal
      surgery--are our estimations of the additional risk accurate?
AB  - OBJECTIVE: Ventriculoperitoneal shunt (VPS)-dependent children require abdominal
      surgery for many reasons. Our objective was to quantify the risk of abdominal
      surgery on VPS survival and to determine whether timing of abdominal intervention
      impacts on shunt outcome. METHODS: Retrospective data collection was performed on
      all children undergoing primary VPS insertion or revision over 2 years (1/1/08
      31/12/10). All shunt interventions were categorised into two groups: those
      undergoing additional "Abdominal surgery" (AS) versus those undergoing "Shunt
      only" (SO). Kaplan-Meier survival curves were devised and analysed using log
      rank. In the AS group, we compared shunt survival for shunts inserted at various
      "Time from abdominal surgery" (TAS). We conducted a control analysis to compare
      shunt survival in AS, SO and a control "clean general surgery" (SG) group. Chi
      squared test was used to determine the cause of shunt failure in these three
      groups. RESULTS: Three hundred and forty two shunts from 109 patients were
      included. Twenty patients contributed 118 shunts to the AS group. Median shunt
      survival was 3.68 months (95% CI = 1.01-6.47) and 22.6 months (95% CI = 8.76
      36.4) in the AS and SO groups, respectively (log-rank = 16.6, p < 0.001). For
      each additional abdominal intervention, the risk of shunt failure increased by
      55.4% (p < 0.001). Median shunt survival was 1.48 months (95% CI = 0.00-3.09, p <
      0.001), if shunt insertion occurred within 1 year of abdominal surgery. Beyond 1
      year, median shunt survival increased five-fold to 7.65 months (95% CI = 0.00
      20.1, log-rank = 23.2, p < 0.001). There was a 29% reduction in risk of shunt
      failure per year interval between a shunt and an abdominal surgery (95% CI = 0.11
      0.44, p < 0.005). Our control analysis confirmed that shunts in the AS group had
      worst survival and infection (p < 0.001). CONCLUSION: Additional abdominal
      surgery shortens VPS lifetime and increases risk of infection. Delaying abdominal
      surgery from a shunt intervention or vice versa by at least 1 year may prolong
      shunt survival.

PMID- 24024874
TI  - The Sexual Function Questionnaire's Medical Impact Scale (SFQ-MIS): validation
      among a sample of first-time mothers.
AB  - INTRODUCTION: Changes in sexual function can be difficult to capture, especially
      when an attempt is made to assess the effects of pregnancy or childbirth on the
      sexual function of first-time mothers. Commonly used sexual function measures are
      limited and fail to account for pregnancy or birth in assessment of function.
      AIMS: The purpose of this study was to explore the utility of the Sexual Function
      Questionnaire Medical Impact Scale (SFQ-MIS) in assessing impact of childbirth on
      sexual function among first-time mothers with infants aged one year or younger.
      METHODS: A total of 255 women completed a cross-sectional, web-based survey.
      Exploratory factor analysis was utilized to assess the factor structure of the
      SFQ-MIS scores in this sample. Variations in SFQ-MIS scores based upon
      participant characteristics were conducted to further evaluate the SFQ-MIS
      scores. MAIN OUTCOME MEASURES: SFQ-MIS score was the primary measure of interest.
      Factors related to pregnancy and childbirth, such as mode of delivery, infant
      date of birth, last menstrual period, need for an episiotomy or perineal
      stitches, breastfeeding status, and score on the Perceived Stress Scale, were
      also assessed in order to further evaluate the validity and predictive capacity
      of the SFQ-MIS. RESULTS: Results indicated one factor that accounted for 58.27%
      of the variance in impact on sexual function due to childbirth. Cronbach's alpha
      coefficient for all five items was acceptable (0.82). Women who were
      breastfeeding (P<0.05), those who had received perineal stitches after a vaginal
      delivery (P<0.05), and those who reported no sexual activity in the past month (P
      < 0.001) experienced significantly greater impact than those who were not
      breastfeeding, those who had not required stitches, and those who had been
      sexually active in the past month. CONCLUSION: The SFQ-MIS appears to be a useful
      and valid indicator of changes in sexual function following childbirth, such as
      those related to arousal, desire, and orgasm.

PMID- 24024875
TI  - Nonaggregational shape-persistent cyclo[6]aramide and its macrocyclic effect
      toward binding secondary ammonium salts in moderately polar media.
AB  - Simply by introducing steric side chains, the shape-persistent cyclo[6]aramides
      were found to exhibit nonaggregational behavior and strong association (3 * 10(4)
      M(-1)) ability in acetone for binding secondary ammonium salt. The complexation
      can be switched in an on-and-off fashion using AgPF6 and TBACl, contrasting
      sharply with their corresponding acyclic pentamer and demonstrating the
      macrocyclic effect. 

PMID- 24024877
TI  - Evaluation of the auto-refraction function of the Nidek OPD-Scan III.
AB  - BACKGROUND: The aim was to evaluate the validity and repeatability of the auto
      refraction function of the Nidek OPD-Scan III (Nidek Technologies, Gamagori,
      Japan) compared with non-cycloplegic subjective refraction. The Nidek OPD-Scan
      III is a new aberrometer/corneal topographer workstation based on the skiascopy
      principle. It combines a wavefront aberrometer, topographer, autorefractor, auto
      keratometer and pupillometer/pupillographer. METHODS: Objective refraction
      results obtained using the Nidek OPD-Scan III were compared with non-cycloplegic
      subjective refraction for 108 eyes of 54 participants (29 female) with a mean age
      of 23.7 +/- 9.5 years. Intra-session and inter-session variability were assessed
      on 14 subjects (28 eyes). RESULTS: The Nidek OPD-Scan III gave slightly more
      negative readings than results obtained by subjective refraction (Nidek mean
      difference -0.19 +/- 0.36 DS, p < 0.01 for sphere; -0.19 +/- 0.35 DS, p < 0.01
      for mean spherical equivalent; -0.002 +/- 0.23 DC, p = 0.91 for cylinder; -0.06
      +/- 0.38 DC, p = 0.30 for J0 and -0.36 +/- 0.31 DC for J45, p = 0.29). Auto
      refractor results for 74 per cent of spherical readings and 60 per cent of
      cylindrical powers were within +/- 0.25 of subjective refraction. There was high
      intra-session and inter-session repeatability for all parameters; 90 per cent of
      inter-session repeatability results were within 0.25 D. CONCLUSION: The Nidek OPD
      Scan III gives valid and repeatable measures of objective refraction when
      compared with non-cycloplegic subjective refraction.

PMID- 24024878
TI  - Influence of endothelial cell protein C receptor on breast cancer development.

PMID- 24024879
TI  - Cat, dog and house dust mite allergen levels on children's soft toys.
AB  - OBJECTIVE: Children's soft toys are known to harbour house dust mite (HDM)
      allergens, but little is known whether they harbour cat or dog allergens. The
      objective of the study was to measure cat (Fel d 1), dog (Can f 1) and HDM
      allergens on children's soft toys. METHODS: Dust was collected from 40 children's
      soft toys and their mattresses. Data were collected on pet ownership. Dust
      samples were analysed for Fel d 1, Can f 1, Der p 1 and Der f 1 by enzyme-linked
      immunosorbent assay (ELISA) and results are expressed as median levels with inter
      quartile ranges. RESULTS: Thirty-five (87.5%) soft toys had detectable Fel d 1
      levels (median: 0.73 ug/g; inter-quartile range: 0.26-2.56 ug/g) while 34 (85%)
      had detectable Can f 1 levels (1.20 ug/g; 0.53-2.68). Correspondingly, 32 (80%)
      mattresses had detectable Fel d 1 levels (0.18 ug/g, 0.07-1.01) while 34 (85%)
      had detectable Can f 1 levels (0.50 ug/g; 0.33-1.06). All mattresses and soft
      toys had detectable HDM allergen (Der p 1 + Der f 1) levels with soft toys
      containing about three times higher levels than mattresses. In homes with cats (n
      = 10) Fel d 1 levels were higher on soft toys than homes without cats (2.49
      versus 0.48 ug/g; p = 0.0009). In homes with dogs (n = 25) Can f 1 levels were
      generally higher on soft toys (1.38 versus 0.63 ug/g; p = 0.10). CONCLUSIONS:
      This study has shown that soft toys can harbour cat and dog allergen as well as
      HDM allergens, some with very high levels. Cat and dog ownership resulted in
      higher Fel d 1 and Can f 1 levels on soft toys and mattresses. The levels of Fel
      d 1, Can f 1 and HDM allergens on soft toys could be of importance to sensitized
      asthmatic children.

PMID- 24024880
TI  - Stereochemistry and solid-state structure of an intrinsically chiral meso
      patterned porphyrin: case study by NMR and single-crystal X-ray diffraction
      analysis.
AB  - A C1-symmerical meso-substituted ABCD-type porphyrin, [5-phenyl-10-(2
      hydroxynaphthyl)-15-(4-hydroxyphenyl)porphyrinato]zinc(II) (1), has been
      synthesized and characterized. The molecular structure of 1 has been determined
      by single-crystal X-ray diffraction analysis. The complex 1 crystallizes in a
      triclinic system with one pair of enantiomeric molecules per unit cell.
      Resolution of the racemic mixture has been achieved by chiral HPLC techniques. In
      particular, the absolute configurations of the enantiomers have been assigned
      from NMR spectroscopic analysis with L-Phe-OMe as the chiral solvating agent
      (CSA). The assignments have also been unambiguously confirmed by single-crystal X
      ray diffraction analysis. The present results suggest that the CSA-NMR anisotropy
      strategy is applicable for the stereochemistry determination of chiral host-guest
      complexes with multiple intermolecular interactions. In addition, the multiple
      intermolecular interactions between the enantiomerically pure porphyrin S-1 and L
      Phe-OMe are proved in the solid state by single-crystal X-ray diffraction
      analysis.

PMID- 24024876
TI  - Glial abnormalities in substance use disorders and depression: does shared
      glutamatergic dysfunction contribute to comorbidity?
AB  - OBJECTIVES: Preclinical and clinical research in neuropsychiatric disorders,
      particularly mood and substance use disorders, have historically focused on
      neurons; however, glial cells-astrocytes, microglia, and oligodendrocytes - also
      play key roles in these disorders. METHODS: Peer-reviewed PubMed/Medline articles
      published through December 2012 were identified using the following keyword
      combinations: glia, astrocytes, oligodendrocytes/glia, microglia, substance use,
      substance abuse, substance dependence, alcohol, opiate, opioid, cocaine,
      psychostimulants, stimulants, and glutamate. RESULTS: Depressive and substance
      use disorders are highly comorbid, suggesting a common or overlapping aetiology
      and pathophysiology. Reduced astrocyte cell number occurs in both disorders.
      Altered glutamate neurotransmission and metabolism - specifically changes in the
      levels/activity of transporters, receptors, and synaptic proteins potentially
      related to synaptic physiology - appear to be salient features of both disorders.
      Glial cell pathology may also underlie the pathophysiology of both disorders via
      impaired astrocytic production of neurotrophic factors.
      Microglial/neuroinflammatory pathology is also evident in both depressive and
      substance use disorders. Finally, oligodendrocyte impairment decreases
      myelination and impairs expression of myelin-related genes in both substance use
      and depressive disorders. CONCLUSIONS: Glial-mediated glutamatergic dysfunction
      is a common neuropathological pathway in both substance use and depression.
      Therefore, glutamatergic neuromodulation is a rational drug target in this
      comorbidity.

PMID- 24024883
TI  - Abstracts of the AABB Annual Meeting and CTTXPO. Denver, Colorado, USA. October
      12-15, 2013.

PMID- 24024881
TI  - Method validation of circulating tumour cell enumeration at low cell counts.
AB  - BACKGROUND: Circulating tumour cells (CTC) are receiving increasing attention as
      prognostic, predictive and pharmacodynamic biomarkers in cancer patients.
      However, their clinical significance can be dependent on an accurate
      determination of CTC around cut-off values at low cell counts (<10 cells/7.5 ml).
      Consequently, we have conducted method validation of the CellSearchTM system
      focusing on clinical samples containing CTC in the cut-off region. METHODS:
      Analytical accuracy was first assessed employing quality controls (QC) and spiked
      healthy volunteer blood specimens. Results were analysed by beta-expectation
      tolerance intervals (BETI). Inter-operator error (6 different readers) was then
      characterised in 38 different patient samples, 68% of which had <=5 CTC and data
      were analysed by beta-content gamma-confidence tolerance intervals (BCTI).
      RESULTS: Results from QCs and spiked blood confirmed a 3-4-fold higher degree of
      imprecision at the low (48 cells, BETI = + 0.288/-0.345, beta = 95%) compared to
      the high QC (987 cells, BETI = +0.065/-0.140, beta = 95%). However, when data for
      individual analysts were interrogated characteristic systematic errors were
      detected. In the analysis of patient samples again individual analysts introduced
      a highly specific error into the interpretation of CTC images, which correlated
      to the level of training and experience. When readers were selected based on BETI
      and BCTI results, the high level of between-operator error (up to 170%) observed
      at CTC of <= 5 was reduced to < 30%. CONCLUSIONS: Inter-operator variability in
      enumeration of CTC at low cell counts can be considerable, but is also
      potentially avoidable by following simple guidance steps.

PMID- 24024884
TI  - Searching the haematology and inflammation archives of Journal of Internal
      Medicine.

PMID- 24024882
TI  - Genetic parameters for milk fatty acids in Danish Holstein cattle based on SNP
      markers using a Bayesian approach.
AB  - BACKGROUND: For several years, in human nutrition there has been a focus on the
      proportion of unsaturated fatty acids (UFA) and saturated fatty acids (SFA) found
      in bovine milk. The positive health-related properties of UFA versus SFA have
      increased the demand for food products with a higher proportion of UFA. To be
      able to change the UFA and SFA content of the milk by breeding it is important to
      know whether there is a genetic component underlying the individual FA in the
      milk. We have estimated the heritability for individual FA in the milk of Danish
      Holstein. For this purpose we used information of SNP markers instead of the
      traditional pedigree relationships. RESULTS: Estimates of heritability were
      moderate within the range of 0.10 for C18:1 trans-11 to 0.34 for C8:0 and C10:0,
      whereas the estimates for saturated fatty acids and unsaturated fatty acids were
      0.14 and 0.18, respectively. Posterior standard deviations were in the range from
      0.07 to 0.17. The correlation estimates showed a general pattern of two groups,
      one group mainly consisting of saturated fatty acids and one group mainly
      consisting of unsaturated fatty acids. The phenotypic correlation ranged from 
      0.95 (saturated fatty acids and unsaturated fatty acids) to 0.99 (unsaturated
      fatty acids and monounsaturated fatty acids) and the genomic correlation for
      fatty acids ranged from -0.29 to 0.91. CONCLUSIONS: The heritability estimates
      obtained in this study are in general accordance with heritability estimates from
      studies using pedigree data and/or a genomic relationship matrix in the context
      of a REML approach. SFA and UFA expressed a strong negative phenotypic
      correlation and a weaker genetic correlation. This is in accordance with the
      theory that SFA is synthesized de novo, while UFA can be regulated independently
      from the regulation of SFA by the feeding regime.

PMID- 24024885
TI  - Five new chalcohalides, Ba3GaS4X (X = Cl, Br), Ba3MSe4Cl (M = Ga, In), and
      Ba7In2Se6F8: syntheses, crystal structures, and optical properties.
AB  - Five new chalcohalides, Ba3GaS4X (X = Cl, Br), Ba3MSe4Cl (M = Ga, In), and
      Ba7In2Se6F8, have been synthesized by conventional high-temperature solid-state
      method. These compounds crystallize in three different interesting structure
      types. Ba3GaQ4X (Q = S, X = Cl, Br; Q = Se, X = Cl) contain zigzag BaX
      pseudolayers and isolated GaQ4 tetrahedra, while Ba3InSe4Cl possesses one Ba-In
      Se pseudolayer and one Ba-Cl pseudolayer, which are stacked alternately along the
      c-direction. Ba7In2Se6F8 is comprised of one-dimensional 1infinity[InSe3]3-
      chains and unique [Ba7F8]6+ chains. In all those mixed anion compounds, the
      halide anions are only connected to alkaline-earth metal through strong ionic
      bonding, while the M (M = Ga, In) cations are only connected to chalcogenide
      anions through covalent bonding. UV-vis-NIR spectroscopy measurements indicate
      that Ba3GaQ4X (Q = S, X = Cl, Br; Q = Se, X = Cl) have band gaps of 2.14, 1.80,
      and 2.05 eV, respectively.

PMID- 24024886
TI  - Comparative developmental toxicity of new aromatic halogenated DBPs in a
      chlorinated saline sewage effluent to the marine polychaete Platynereis
      dumerilii.
AB  - Using seawater for toilet flushing may introduce high levels of bromide and
      iodide into a city's sewage treatment works, and result in the formation of
      brominated and iodinated disinfection byproducts (DBPs) during chlorination to
      disinfect sewage effluents. In a previous study, the authors' group has detected
      the presence of many brominated DBPs and identified five new aromatic brominated
      DBPs in chlorinated saline sewage effluents. The presence of brominated DBPs in
      chlorinated saline effluents may pose adverse implications for marine ecology. In
      this study, besides the detection and identification of another seven new
      aromatic halogenated DBPs in a chlorinated saline sewage effluent, their
      developmental toxicity was evaluated using the marine polychaete Platynereis
      dumerilii. For comparison, the developmental toxicity of some commonly known
      halogenated DBPs was also examined. The rank order of the developmental toxicity
      of 20 halogenated DBPs was 2,5-dibromohydroquinone > 2,6-diiodo-4-nitrophenol >=
      2,4,6-triiodophenol > 4-bromo-2-chlorophenol >= 4-bromophenol > 2,4-dibromophenol
      >= 2,6-dibromo-4-nitrophenol > 2-bromo-4-chlorophenol > 2,6-dichloro-4
      nitrophenol > 2,4-dichlorophenol > 2,4,6-tribromophenol > 3,5-dibromo-4
      hydroxybenzaldehyde > bromoform >= 2,4,6-trichlorophenol > 2,6-dibromophenol >
      2,6-dichlorophenol > iodoacetic acid >= tribromoacetic acid > bromoacetic acid >
      chloroacetic acid. On the basis of developmental toxicity data, a quantitative
      structure-activity relationship (QSAR) was established. The QSAR involved two
      physical-chemical property descriptors (log P and pKa) and two electronic
      descriptors (the lowest unoccupied molecular orbital energy and the highest
      occupied molecular orbital energy) to indicate the transport, biouptake, and
      biointeraction of these DBPs. It can well predict the developmental toxicity of
      most of the DBPs tested. 

PMID- 24024887
TI  - Efficacy of electroconvulsive therapy: is it in the BDNF gene?

PMID- 24024888
TI  - Donor-recipient genetic diversity: the role of?pharmacogenomics in kidney
      transplantation.

PMID- 24024891
TI  - Institutional Profile: University of Chicago Center for Personalized
      Therapeutics: research, education and implementation science.
AB  - Pharmacogenomics is aimed at advancing our knowledge of the genetic basis of
      variable drug response. The Center for Personalized Therapeutics within the
      University of Chicago comprises basic, translational and clinical research as
      well as education including undergraduate, graduate, medical students,
      clinical/postdoctoral fellows and faculty. The Committee on Clinical Pharmacology
      and Pharmacogenomics is the educational arm of the Center aimed at training
      clinical and postdoctoral fellows in translational pharmacology and
      pharmacogenomics. Research runs the gamut from basic discovery and functional
      studies to pharmacogenomic implementation studies to evaluate physician adoption
      of genetic medicine. The mission of the Center is to facilitate research,
      education and implementation of pharmacogenomics to realize the true potential of
      personalized medicine and improve the lives of patients. 

PMID- 24024892
TI  - Irreversible hepatotoxicity after administration of trabectedin to a pleiomorphic
      sarcoma patient with a rare ABCC2 polymorphism: a case report.
AB  - We describe here the case of a 60-year old male patient treated for an extensive
      local progression of a pleiomorphic sarcoma on the right tibial crest with second
      line trabectedin. Two cycles were administrated before a major liver toxicity was
      retrieved, with both cytolytic and cholestatic hepatitis quickly associated with
      irreversible jaundice. The radiological, histological, chemistry and
      pharmacogenetic investigations led us to diagnose chronic hepatobiliary toxicity
      with portal fibrosis, cholangiolitis damages and chronic hepatopathy. The patient
      had a deficient variant genotype of ABCC2 (c.-24TT, c.4488CT and c.4544GA), which
      has been suggested to play a role in excretion of toxic metabolites of
      trabectedin. This case report is, to our knowledge, the first description of
      trabectedin's irreversible liver toxicity in a human patient. Supported by a
      thorough review of the literature, this hepatitis is thought to have resulted
      from a multihit process involving genetic variants of ABC proteins and
      comedication. 

PMID- 24024893
TI  - A clinical conundrum: the detrimental effect of TNF antagonists in multiple
      sclerosis.
AB  - Although TNF antagonists are efficacious in treating a range of autoimmune
      conditions, they exacerbate or even promote multiple sclerosis (MS)--a clinical
      finding that has been a conundrum for over a decade and has been a source of
      debate regarding the role of these drugs and of TNF signaling in the development
      of demyelinating disease. Recent work investigating the functional consequences
      of MS-associated genetic variation in the gene encoding TNFR1 has demonstrated
      that genetic risk drives the production of a novel, endogenous TNF antagonist.
      This mirrors the clinical experience with the drugs and indicates that the net
      effect of TNF function in MS development is a protective one, warranting a re
      evaluation of the studies that have contributed to our understanding of TNF
      signaling in inflammation, immunoregulation and neuroprotection, to determine how
      future research can be directed towards targeting this pathway for therapeutic
      benefit.

PMID- 24024894
TI  - Multiomics medicine in oncology: assessing effectiveness, cost-effectiveness and
      future research priorities for the molecularly unique individual.
AB  - The development of genomic technologies has ushered in the era of
      pharmacogenomics. However, discoveries and clinical use of targeted therapies are
      still in their infancy. A focus on monogenic pharmacogenetic traits may
      contribute to this lack of progress. Variation in drug response is likely a
      complex paradigm involving not only genomic factors but proteomic, metabolomic
      and epigenomic influences. The incorporation of these omics elements into
      pharmaceutical development and clinical decision-making will ultimately require
      the use of methods to determine clinical and economic value. Current
      methodologies and guidelines for determining clinical effectiveness and cost
      effectiveness may have limited applicability to the increasingly personalized
      nature of omics treatment strategies. Using examples from oncology, this article
      argues for the adaptation and tailoring of three existing methods for ensuring
      development and clinical use of multiomics-guided therapies that are effective,
      safe and offer value for money. 

PMID- 24024895
TI  - CYP2C9 and ABCG2 polymorphisms as risk factors for developing adverse drug
      reactions in renal transplant patients taking fluvastatin: a case-control study.
AB  - AIM: To investigate whether an association exists between fluvastatin-induced
      adverse drug reactions (ADRs) and polymorphisms in genes encoding the
      metabolizing enzyme CYP2C9 and the drug transporter ABCG2 in renal transplant
      recipients (RTRs). MATERIALS & METHODS: Fifty-two RTRs that experienced
      fluvastatin ADRs and 52 controls matched for age, gender, dose of fluvastatin and
      immunosuppressive use were enrolled in the study. Genotyping for CYP2C9*2, *3 and
      ABCG2 421C>A variants was performed by real-time PCR. RESULTS: CYP2C9 homozygous
      and heterozygous mutant allele (*2 or *3) carriers had 2.5-times greater odds of
      developing adverse effects (chi2 = 4.370; degrees of freedom = 1; p = 0.037; phi
      = 0.21, odds ratio [OR]: 2.44; 95% CI: 1.05-5.71). Patients who were the carriers
      of at least one mutant CYP2C9 allele (*2 or *3) and who were receiving CYP2C9
      inhibitors, had more than six-times greater odds of having adverse effects than
      those without the inhibitor included in their therapy (p = 0.027; OR: 6.59; 95%
      CI: 1.24-35.08). Patients with ABCG2 421CA or AA (taken together) had almost four
      times greater odds of developing adverse effects than those with ABCG2 421CC
      genotype (chi2 = 6.190; degrees of freedom = 1; p = 0.013; phi = 0.24, OR: 3.81;
      95% CI: 1.27-11.45). Patients with A allele had 2.75-times (95% CI: 1.02-7.40)
      greater odds of developing adverse effects than those with C allele. CONCLUSION:
      Our preliminary data demonstrate an association between fluvastatin-induced ADRs
      in RTRs and genetic variants in the CYP2C9 and ABCG2 genes.

PMID- 24024896
TI  - ABCC11/MRP8 polymorphisms affect 5-fluorouracil-induced severe toxicity and
      hepatic expression.
AB  - AIM: Because 5-fluorodeoxyuridine monophosphate (5-FdUMP), an anabolic active
      metabolite of 5-fluorouracil (5-FU), is a substrate of MRP8 (encoded by ABCC11),
      we investigated whether ABCC11 polymorphisms play a role in severe toxicity of 5
      FU. PATIENTS & METHODS: Genomic DNA from 672 cancer patients treated with 5-FU
      monotherapy and with documented toxicity according to WHO criteria was genotyped
      for 12 ABCC11 tag SNPs. Functional impact of polymorphisms was assessed in a
      Caucasian human liver cohort (n = 150) and by recombinant expression of MRP8
      protein variants. RESULTS: Univariate and multivariate analysis identified
      rs17822471 (G>A, T546M) as risk factor of severe leukopenia (p = 0.021, odds
      ratio [95%CI]: 3.31 [1.26-8.66]) but not of other toxicity types. MRP8 protein
      expression in human liver was 1.7-fold lower in carriers compared with wild-type
      (p = 0.02). Recombinant expression confirmed the effect of T546M on protein
      expression. CONCLUSION: Since MRP8 is expressed in bone marrow blasts and
      leukocytes, lower expression may lead to intracellular accumulation of 5-FdUMP
      and increased risk of leukopenia.

PMID- 24024897
TI  - RRM1 and RRM2 pharmacogenetics: association with phenotypes in HapMap cell lines
      and acute myeloid leukemia patients.
AB  - BACKGROUND: Ribonucleotide reductase catalyzes an essential step in the cellular
      production of deoxyribonucleotide triphosphates and has been associated with
      clinical outcome in cancer patients receiving nucleoside analog-based
      chemotherapy. MATERIALS & METHODS: In the current study, we sequenced the genes
      RRM1 and RRM2 in genomic DNA from HapMap cell lines with European (Utah residents
      with northern and western European ancestry [CEU]; n = 90) or African (Yoruba
      people in Ibadan, Nigeria [YRI]; n = 90) ancestry. RESULTS: We identified 44
      genetic variants including eight coding SNPs in RRM1 and 15 SNPs including one
      coding SNP in RRM2. RRM1 and RRM2 mRNA expression levels were significantly
      correlated with each other in both CEU and YRI lymphoblast cell lines, and in
      leukemic blasts from acute myeloid leukemia (AML) patients (AML97, n = 89; AML02,
      n = 187). Additionally, RRM1 expression was higher among patient features
      indicative of a high relapse hazard. We evaluated SNPs within the RRM1 and RRM2
      genes in the HapMap lymphoblast cell lines from CEU and YRI panels for
      association with expression and cytarabine chemosensitivity. SNPs of potential
      significance were further evaluated in AML patients. RRM1 SNPs rs1042919 (which
      occurs in linkage disequilbrium with multiple other SNPs) and promoter SNP
      rs1561876 were associated with intracellular 1-beta-D-arabinofuranosyl-CTP
      levels, response after remission induction therapy, risk of relapse and overall
      survival in AML patients receiving cytarabine and cladribine. CONCLUSION: These
      results suggest that SNPs within ribonucleotide reductase might be helpful
      predictive markers of response to nucleoside analogs and should be further
      validated in larger cohorts.

PMID- 24024898
TI  - Impact of CYP3A5 genotype on tacrolimus versus midazolam clearance in renal
      transplant recipients: new insights in CYP3A5-mediated drug metabolism.
AB  - BACKGROUND & AIM: In vitro studies have identified both midazolam and tacrolimus
      as dual CYP3A4 and CYP3A5 substrates. In vivo; however, the CYP3A5 genotype has a
      marked impact on tacrolimus pharmacokinetics, whereas it seems not to affect
      midazolam pharmacokinetics. The aim of the current study was to explore this
      paradigm in a relevant clinical setting. PATIENTS & METHODS: A case-control study
      in 80 tacrolimus-treated renal transplant recipients comparing systemic and
      apparent oral midazolam clearance and tacrolimus pharmacokinetics in CYP3A5
      expressers (CYP3A5*1 allele carriers) and CYP3A5 nonexpressers (CYP3A5*3/*3) was
      performed. RESULTS: CYP3A5 expressers display an approximately 2.4-fold higher
      tacrolimus clearance as compared with CYP3A5 nonexpressers, whereas there are no
      differences in systemic and apparent oral midazolam clearance. CONCLUSION: These
      data confirm that in vivo CYP3A5 plays an important role in tacrolimus
      metabolism, while its contribution to midazolam metabolism in a relevant study
      population is limited. Furthermore, these data suggest that midazolam is to be
      considered as a phenotypic probe for in vivo CYP3A4 activity rather than combined
      CYP3A4 and CYP3A5 activity.

PMID- 24024899
TI  - Human dopamine transporter gene: differential regulation of 18-kb haplotypes.
AB  - AIM: Since previous functional studies of short haplotypes and polymorphic sites
      of SLC6A3 have shown variant-dependent and drug-sensitive promoter activity, this
      study aimed to understand whether a large SLC6A3 regulatory region, containing
      these small haplotypes and polymorphic sites, can display haplotype-dependent
      promoter activity in a drug-sensitive and pathway-related manner. MATERIALS &
      METHODS: By creating and using a single copy number luciferase-reporter vector,
      we examined regulation of two different SLC6A3 haplotypes (A and B) of the 5' 18
      kb promoter and two known downstream regulatory variable number tandem repeats by
      17 drugs in four different cellular models. RESULTS: The two regulatory
      haplotypes displayed up to 3.2-fold difference in promoter activity. The
      regulations were drug selective (37.5% of the drugs showed effects), and both
      haplotype and cell type dependent. Pathway analysis revealed at least 13 main
      signaling hubs targeting SLC6A3, including histone deacetylation, AKT, PKC and
      CK2 alpha-chains. CONCLUSION: SLC6A3 may be regulated via either its promoter or
      the variable number tandem repeats independently by specific signaling pathways
      and in a haplotype-dependent manner. Furthermore, we have developed the first
      pathway map for SLC6A3 regulation. These findings provide a framework for
      understanding complex and variant-dependent regulations of SLC6A3.

PMID- 24024903
TI  - Amplification of surface-initiated ring-opening metathesis polymerization of 5
      (perfluoro-n-alkyl)norbornenes by macroinitiation.
AB  - This article reports the enhanced rate of the surface-initiated polymerization
      (SIP) of 5-(perfluoro-n-alkyl)norbornenes (NBFn) by combining two SIP techniques,
      namely surface-initiated atom-transfer polymerization (SI-ATRP) to grow a
      macroinitiator and surface-initiated ring-opening metathesis polymerization (SI
      ROMP) to produce the final coating. This polymerization approach promotes the
      rapid growth of dense partially fluorinated coatings that are highly hydrophobic
      and oleophobic and yield thicknesses from 4-12 MUm. Specifically, the growth rate
      and the limiting thickness of pNBFn with different side chain lengths (n = 4, 6,
      8, and 10) at various monomer concentrations and temperatures are evaluated
      through two approaches: growing the polymer from an initiator-terminated
      monolayer (control) or from a modified poly(2-hydroxyethyl methacrylate) (PHEMA)
      macroinitiator. X-ray photoelectron spectroscopy (XPS) analysis shows that 38% of
      the hydroxyl termini in the macroinitiator react with a norbornenyl diacid
      chloride (NBDAC) molecule, and 7% of such anchored norbornenyl groups react with
      a catalyst molecule. The kinetic data have been modeled to determine the
      propagation velocity and the termination rate constant. The PHEMA macroinitiator
      provides thicker films and faster growth as compared to the monolayer, achieving
      a 12 MUm thick coating of pNBF8 in 15 min. Increasing the monomer side chain
      length, n, from 4 to 10 improves the growth rate and the limiting polymer
      thickness. Performing the polymerization process at higher temperature increases
      the growth rate and the limiting thickness as evidenced by an increase in the
      film growth rate constant. Arrhenius plots show that the reactions involved in
      the macroinitiation process exhibit lower activation energies than those formed
      from a monolayer. Electrochemical impedance spectroscopy reveals that the films
      exhibit resistance against ion transport in excess of 1 * 10(10) Omega.cm(2). 

PMID- 24024901
TI  - Tailoring mTOR-based therapy: molecular evidence and clinical challenges.
AB  - The mTOR signaling pathway integrates inputs from a variety of upstream stimuli
      to regulate diverse cellular processes including proliferation, growth, survival,
      motility, autophagy, protein synthesis and metabolism. The mTOR pathway is
      dysregulated in a number of human pathologies including cancer, diabetes,
      obesity, autoimmune disorders, neurological disease and aging. Ongoing clinical
      trials testing mTOR-targeted treatments number in the hundreds and underscore its
      therapeutic potential. To date mTOR inhibitors are clinically approved to prevent
      organ rejection, to inhibit restenosis after angioplasty, and to treat several
      advanced cancers. In this review we discuss the continuously evolving field of
      mTOR pharmacogenomics, as well as highlight the emerging efforts in identifying
      diagnostic and prognostic markers, including miRNAs, in order to assess
      successful therapeutic responses. 

PMID- 24024900
TI  - Pharmacogenetics of paraoxonase activity: elucidating the role of high-density
      lipoprotein in disease.
AB  - PON1 is a key component of high-density lipoproteins (HDLs) and is at least
      partially responsible for HDL's antioxidant/atheroprotective properties. PON1 is
      also associated with numerous human diseases, including cardiovascular disease,
      Parkinson's disease and cancer. In addition, PON1 metabolizes a broad variety of
      substrates, including toxic organophosphorous compounds, statin adducts,
      glucocorticoids, the likely atherogenic L-homocysteine thiolactone and the quorum
      sensing factor of Pseudomonas aeruginosa. Numerous cardiovascular and
      antidiabetic pharmacologic agents, dietary macronutrients, lifestyle factors and
      antioxidant supplements affect PON1 expression and enzyme activity levels. Owing
      to the importance of PON1 to HDL function and its individual association with
      diverse human diseases, pharmacogenomic interactions between PON1 and the various
      factors that alter its expression and activity may represent an important
      therapeutic target for future investigation. 

PMID- 24024904
TI  - Plum coatings of lemongrass oil-incorporating carnauba wax-based nanoemulsion.
AB  - Nanoemulsions containing lemongrass oil (LO) were developed for coating plums and
      the effects of the nanoemulsion coatings on the microbial safety and
      physicochemical storage qualities of plums during storage at 4 and 25  degrees C
      were investigated. The emulsions used for coating were produced by mixing a
      carnauba wax-based solution (18%, w/w) with LO at various concentrations (0.5% to
      4.0%, w/w) using dynamic high pressure processing at 172 MPa. The coatings were
      evaluated for their ability to inhibit the growth of Salmonella Typhimurium and
      Escherichia coli O157:H7 and their ability to preserve various physicochemical
      qualities of plums. Uniform and continuous coatings on plums, formed with stable
      emulsions, initially inhibited S. Typhimurium and E. coli O157:H7 by 0.2 to 2.8
      and 0.8 to 2.7 log CFU/g, respectively, depending on the concentration of LO and
      the sequence of coating. The coatings did not significantly alter the flavor,
      fracturability, or glossiness of the plums. The antimicrobial effects of the
      coatings against S. Typhimurium and E. coli O157:H7 were demonstrated during
      storage at 4 and 25  degrees C. The coatings reduced weight loss and ethylene
      production by approximately 2 to 3 and 1.4 to 4.0 fold, respectively, and also
      retarded the changes in lightness and the concentration of phenolic compounds in
      plums during storage. The firmness of coated plums was generally higher than
      uncoated plums when stored at 4  degrees C and plum respiration rates were
      reduced during storage. Coatings containing nanoemulsions of LO have the
      potential to inhibit Salmonella and E. coli O157:H7 contamination of plums and
      may extend plum shelf life. 

PMID- 24024907
TI  - A meta-analysis of carbon nanotube pulmonary toxicity studies--how physical
      dimensions and impurities affect the toxicity of carbon nanotubes.
AB  - This article presents a regression-tree-based meta-analysis of rodent pulmonary
      toxicity studies of uncoated, nonfunctionalized carbon nanotube (CNT) exposure.
      The resulting analysis provides quantitative estimates of the contribution of CNT
      attributes (impurities, physical dimensions, and aggregation) to pulmonary
      toxicity indicators in bronchoalveolar lavage fluid: neutrophil and macrophage
      count, and lactate dehydrogenase and total protein concentrations. The method
      employs classification and regression tree (CART) models, techniques that are
      relatively insensitive to data defects that impair other types of regression
      analysis: high dimensionality, nonlinearity, correlated variables, and
      significant quantities of missing values. Three types of analysis are presented:
      the RT, the random forest (RF), and a random-forest-based dose-response model.
      The RT shows the best single model supported by all the data and typically
      contains a small number of variables. The RF shows how much variance reduction is
      associated with every variable in the data set. The dose-response model is used
      to isolate the effects of CNT attributes from the CNT dose, showing the shift in
      the dose-response caused by the attribute across the measured range of CNT doses.
      It was found that the CNT attributes that contribute the most to pulmonary
      toxicity were metallic impurities (cobalt significantly increased observed
      toxicity, while other impurities had mixed effects), CNT length (negatively
      correlated with most toxicity indicators), CNT diameter (significantly positively
      associated with toxicity), and aggregate size (negatively correlated with cell
      damage indicators and positively correlated with immune response indicators).
      Increasing CNT N2 -BET-specific surface area decreased toxicity indicators. 

PMID- 24024906
TI  - Silver nanoparticles incite size- and dose-dependent developmental phenotypes and
      nanotoxicity in zebrafish embryos.
AB  - Nanomaterials possess distinctive physicochemical properties and promise a wide
      range of applications, from advanced technology to leading-edge medicine.
      However, their effects on living organisms remain largely unknown. Here we report
      that the purified silver nanoparticles (Ag NPs) (97 +/- 13 nm) incite specific
      developmental stage embryonic phenotypes and nanotoxicity in a dose-dependent
      manner, upon acute exposure of given stage embryos to the NPs (0-24 pM) for only
      2 h. The critical concentrations of the NPs that cause 50% of embryos to develop
      normally for cleavage, early gastrula, early segmentation, late segmentation, and
      hatching stage zebrafish embryos are 3.5, 4, 6, 6, and 8 pM, respectively,
      showing that the earlier developmental stage embryos are much more sensitive to
      the effects of the NPs than the later stage embryos. Interestingly, distinctive
      phenotypes (head abnormality and no eyes) are observed only in cleavage and early
      gastrula stage embryos treated with the NPs, showing the stage-specific effects
      of the NPs. By comparing these Ag NPs with smaller Ag NPs (13.1 +/- 2.5 nm), we
      found that the embryonic phenotypes strikingly depend upon the sizes of Ag NPs
      and embryonic developmental stages. These notable findings suggest that the Ag
      NPs are unlike any conventional chemicals or ions. They can potentially enable
      target-specific study and therapy for early embryonic development in size-, stage
      , dose-, and exposure duration-dependent manners. 

PMID- 24024905
TI  - Pancreatic cancer.
AB  - In recent years, it has become clear that the current standard therapeutic
      options for pancreatic cancer are not adequate and still do not meet the criteria
      to cure patients suffering from this lethal disease. Although research over the
      past decade has shown very interesting and promising new therapeutic options for
      these patients, only minor clinical success was achieved. Therefore, there is
      still an urgent need for new approaches that deal with early detection and new
      therapeutic options in pancreatic cancer. To provide optimal care for patients
      with pancreatic cancer, we need to understand better its complex molecular
      biology and thus to identify new target molecules that promote the proliferation
      and resistance to chemotherapy of pancreatic cancer cells. In spite of
      significant progress in curing cancers with chemotherapy, pancreatic cancer
      remains one of the most resistant solid tumour cancers and many studies suggest
      that drug-resistant cancer cells are the most aggressive with the highest relapse
      and metastatic rates. In this context, activated Notch signalling is strongly
      linked with chemoresistance and therefore reflects a rational new target to
      circumvent resistance to chemotherapy in pancreatic cancer. Here, we have focused
      our discussion on the latest research, current therapy options and recently
      identified target molecules such as Notch-2 and the heparin-binding growth factor
      midkine, which exhibit a wide range of cancer-relevant functions and therefore
      provide attractive new therapeutic target molecules, in terms of pancreatic
      cancer and other cancers also. LINKED ARTICLES: This article is part of a themed
      section on Midkine. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24024908
TI  - Osteoprotegerin expression during the micro- and macrometastatic phases of the
      osteoblastic metastasis in prostate cancer: therapeutic implications.
AB  - INTRODUCTION: Osteoprotegerin (OPG) acts as a soluble decoy receptor for the bone
      marrow stroma cell-derived and osteoblast-derived receptor activator of nuclear
      factor-kB ligand (RANKL), thus regulating the RANK-mediated osteoclastogenesis
      and osteoclast-mediated bone resorption at the metastatic niche of cancer in
      skeleton. AREAS COVERED: This article discusses the 'key' role of OPG expression
      during the early events of cancer cell invasion into the bone matrix and the
      subsequent events underlying the formation of osteoblastic metastasis, a unique
      event observed in human prostate cancer biology. EXPERT OPINION: Understanding
      the cellular and molecular events implicated in bone metastasis can facilitate
      designing new therapeutic strategies for targeting early and/or late events in
      the metastasis processes. The RANKL/RANK/OPG pathway is a key regulator of
      pathological bone metabolism in metastatic sites. Targeted manipulation of these
      molecules may provide sustainable antitumor responses.

PMID- 24024909
TI  - Detection of Vibrio parahaemolyticus, Vibrio vulnificus and Vibrio cholerae with
      respect to seasonal fluctuations in temperature and plankton abundance.
AB  - Over a 1-year period, bi-monthly estuarine surface water and plankton samples (63
      200 and > 200 MUm fractions) were assayed by polymerase chain reaction for the
      prevalence of total Vibrio parahaemolyticus, V. vulnificus and V. cholerae and
      select genes associated with clinical strains found in each species. Neither
      temperature nor plankton abundance was a significant correlate of total V.
      parahaemolyticus; however, the prevalence of genes commonly associated with
      clinical strains (trh, tdh, ORF8) increased with temperature and copepod
      abundance (P < 0.05). The prevalence of total V. vulnificus and the siderophore
      related viuB gene also increased with temperature and copepod and decapod
      abundance (P < 0.001). Temperature and copepod abundance also covaried with the
      prevalence of V. cholerae (P < 0.05), but there was no significant relationship
      with ctxA or other genes commonly found in clinical strains. Results show that
      genes commonly associated with clinical Vibrio strains were more frequently
      detected in association with chitinous plankton. We conclude that V.
      parahaemolyticus, V. vulnificus, V. cholerae and subpopulations that harbour
      genes common to clinical strains respond distinctly to seasonal changes in
      temperature as well as shifts in the taxonomic composition of discrete plankton
      fractions.

PMID- 24024910
TI  - The role of neuronavigation-guided functional MRI and diffusion tensor
      tractography along with cortical stimulation in patients with eloquent cortex
      lesions.
AB  - OBJECTIVE. To effectively combine functional MRI (fMRI), diffusion tensor
      tractography (both guided by neuronavigation) along with cortical stimulation
      (CS) for surgery of eloquent cortex (EC) lesions. MATERIALS AND METHOds. Fifteen
      patients with lesions adjacent to the eloquent motor and sensory cortex were
      included. Preoperative fMRI and diffusion tensor imaging were performed and then
      integrated into the neuronavigation system. Intraoperative CS of sensory/motor
      cortex was performed to localize the EC under awake condition and this was
      correlated with areas active on fMRI utilizing neuronavigation. For excision of
      the deeper structures, CS, and tractography guided by neuronavigation were
      utilized. RESULTS. A total of 127 cortical sites were evaluated with CS in 15
      patients. The overall sensitivity, specificity, and accuracy of fMRI were 79%,
      85%, and 82%, respectively, keeping the areas positive on CS as a referential
      parameter. Tractography helped in resecting the deeper areas of the tumor, but
      was not very accurate due to brain shift. However, it was useful in roughly
      assessing the deeper areas close to the long tracts. The risk of developing
      persistent neurological deficits was 6%. Pathologies included gliomas in ten
      patients, cavernous malformation in two patients, meningioma in one patient, and
      focal cortical dysplasia and Dysembryonic neuroepithelial tumor in one patient
      each. Near total excision was achieved in 7/10 (> 95% excision) gliomas and a
      total excision in all others lesions. CONCLUSIONS. Lesions directly over the EC
      present a special surgical challenge. The challenge lies in excising these
      lesions without producing any deficits. These goals may be achieved better by
      combined use of multimodal neuronavigation (fMRI and tractography) and
      intraoperative mapping with CS under awake conditions.

PMID- 24024911
TI  - Use of pollen and ancient DNA as conservation baselines for offshore islands in
      New Zealand.
AB  - Islands play a key role globally in the conservation of endemic species. Many
      island reserves have been highly modified since human colonization, and their
      restoration and management usually occur without knowledge of their prehuman
      state. However, conservation paleoecology is increasingly being recognized as a
      tool that can help to inform both restoration and conservation of island reserves
      by providing prehuman vegetation baselines. Many of New Zealand's mammal-free
      offshore islands are foci for biological diversity conservation and, like many
      islands in the Polynesian region, were deforested following initial human
      settlement. Therefore, their current restoration, replanting, and management are
      guided either by historic vegetation descriptions or the occurrence of species on
      forested islands. We analyzed pollen and ancient DNA in soil cores from an
      offshore island in northern New Zealand. The result was a 2000-year record of
      vegetation change that began >1200 years before human settlement and spanned 550
      years of human occupation and 180 years of forest succession since human
      occupation ceased. Between prehuman and contemporary forests there was nearly a
      complete species turnover including the extirpation of a dominant conifer and a
      palm tree. The podocarp-dominated forests were replaced by a native but novel
      angiosperm-dominated forest. There is no modern analog of the prehuman forests on
      any northern New Zealand island, and those islands that are forested are
      dominated by angiosperms which are assumed to be climax forests. The pollen and
      DNA evidence for conifer- and palm-rich forests in the prehuman era challenge
      this climax forest assumption. Prehuman vegetation records can thus help to
      inform future restoration of degraded offshore islands by informing the likely
      rate and direction of successional change; helping to determine whether natural
      rates of succession are preferable to more costly replanting programs; and
      providing past species lists if restoration replanting is desired.

PMID- 24024912
TI  - Aerobic synthesis of substituted quinoline from aldehyde and aniline: copper
      catalyzed intermolecular C-H active and C-C formative cyclization.
AB  - An efficient method for the direct synthesis of substituted quinolines from
      anilines and aldehydes through C-H functionalization, C-C/C-N bond formation, and
      C-C bond cleavage has been developed. The method is simple and practical and
      employs air as an oxidant. 

PMID- 24024913
TI  - Synthesis of a potential intermediate for TMC-95A via an organocatalyzed aldol
      reaction.
AB  - N-Prolinylanthranilamide-based pseudopeptide organocatalyst 14 was shown to
      promote enantioselective direct aldol reaction of 7-iodoisatin and 2,2-dimethyl
      1,3-dioxan-5-one with 90% conversion (75% isolated yield), 90%
      enantioselectivity, and 23:1 diastereoselectivity. To demonstrate the synthetic
      utility of this chemistry, the racemic aldol reaction product was converted in
      five steps to a potential intermediate for construction of the natural product
      TMC-95A. 

PMID- 24024914
TI  - The research rolls on.

PMID- 24024915
TI  - STICH 2: does decompression have a role in superficial intracerebral hematoma?
AB  - The recently published second Surgical Trial in Intracerebral Haemorrhage (STICH
      2) tested whether surgical evacuation of superficial spontaneous intracerebral
      haemorrhage was effective at reducing death and disability at 6 months after
      onset. Participants were randomised to a policy of early surgical intervention or
      initial medical management alone within 48 hours of symptom onset. After
      enrolling 601 patients across 78 centres in 27 countries, intention to treat
      analysis showed no difference in outcome. Time to intervention was a median of 26
      hours after symptom onset in the surgical arm, and craniotomy accounted for 98%
      of all surgical procedures. The interpretation of the overall neutral result is
      confounded by a high proportion of crossovers from the medical management arm of
      the study, predominantly of more severely affected patients. Further analysis may
      clarify whether decompressive surgery late after superficial intracerebral
      haemorrhage has any role in management. 

PMID- 24024916
TI  - Revascularization-outcome paradox: not only time and collaterals status, but also
      complete recanalization contribute to good neurological outcome.
AB  - The rate of successful recanalization in endovascular trials has not always
      mirrored the rate of good clinical outcomes, creating a revascularization-outcome
      paradox. In early experience with the new generation of stent-based thrombectomy
      devices, 45-77% of patients have achieved good 90-day outcomes despite treatment
      up to eight-hours after symptom onset. These rates of good functional outcome are
      clearly higher than those previously reported with other endovascular strategies.
      We propose that among the factors influencing this difference is the far higher
      complete recanalization rate and the high ratio of Thrombolysis in Myocardial
      Infarction 3/Thrombolysis in Myocardial Infarction 2 recanalization obtained with
      stent retrievers in comparison with previous generation mechanical thrombectomy
      devices. Recently, we achieved Thrombolysis in Myocardial Infarction 3 in 94% of
      patients and Thrombolysis in Myocardial Infarction 2 in 6% in a series of
      patients with acute middle cerebral artery occlusions who were managed with stent
      thrombectomy within eight-hours of symptom onset. Good outcomes were achieved in
      77%. Extent of recanalization appears to interact with time and collateral supply
      in determining clinical outcomes. 

PMID- 24024917
TI  - Program for the epidemiological evaluation of stroke in Tandil, Argentina
      (PREVISTA) study: rationale and design.
AB  - The availability of population-based epidemiological data on the incident risk of
      stroke is very scarce in Argentina and other Latin American countries. In
      response to the priorities established by the World Health Organization and the
      United Nations, PREVISTA was envisaged as a population-based program to determine
      the risk of first-ever and recurrent stroke and transient ischemic attack
      incidence and mortality in Tandil, Buenos Aires, Argentina. The study will be
      conducted according to Standardized Tools for Stroke Surveillance (STEPS Stroke)
      methodology and will enroll all new (incident) and recurrent consecutive cases of
      stroke and transient ischemic attack in the City of Tandil between May 1st, 2013
      and April 30, 2015. The study will include patients with ischemic stroke, non
      traumatic primary intracerebral hemorrhage, subarachnoid hemorrhage, and
      transient ischemic attack. To ensure the inclusion of every cerebrovascular event
      during an observation period of two years, we will instrument an 'intensive
      screening program', consisting of a comprehensive daily tracking of every
      potential event of stroke or transient ischemic attack using multiple overlapping
      sources. Mortality would be determined during follow-up for every enrolled
      patient. Also, fatal community events would be screened daily through revision of
      death certificates at funeral homes and local offices of vital statistics. All
      causes of death will be adjudicated by an ad-hoc committee. The close population
      of Tandil is representative of a large proportion of Latin-American countries
      with low- and middle-income economies. The findings and conclusions of PREVISTA
      may provide data that could support future health policy decision-making in the
      region. 

PMID- 24024918
TI  - Revascularization with stenting of the nonacute vertebrobasilar artery occlusion.

PMID- 24024919
TI  - ACTA2 is not a major genetic risk gene for Chinese patients with moyamoya
      disease.

PMID- 24024920
TI  - Exenatide in acute ischemic stroke.

PMID- 24024921
TI  - Haemorrhagic stroke proportion reassessment at the emergency department gives the
      first green light - a necessary follow-up in Romania.

PMID- 24024922
TI  - Signal intensity ratio as a novel measure of hemodynamic significance for
      intracranial atherosclerosis.

PMID- 24024923
TI  - First thrombolysis in acute stroke with tenecteplase in Congo.

PMID- 24024924
TI  - Intravenous thrombolytic therapy for acute ischemic stroke in Tuzla Canton,
      Bosnia and Herzegovina.

PMID- 24024925
TI  - Effect of prior treatment with different statins on stroke severity and
      functional outcome at discharge in patients with acute ischemic stroke.

PMID- 24024926
TI  - Prevalence of intracranial stenosis and silent cerebral infarcts in children with
      sickle cell anemia and low risk of stroke.

PMID- 24024927
TI  - Hydration status and stroke-in-evolution after ischemic stroke: a preliminary
      study.

PMID- 24024928
TI  - Platelet-derived CXCL12 (SDF-1alpha): basic mechanisms and clinical implications.
AB  - Platelets are a major source of CXCL12 (stromal cell-derived factor -1alpha, SDF
      1alpha) and store CXCL12 as part of their alpha-granule secretome. Platelet
      activation enhances surface expression and release of CXCL12. Platelets and
      megakaryocytes express CXCR4, the major receptor for CXCL12, and interaction of
      CXCL12 with CXCR4 regulates megakaryopoiesis and the function of circulating
      platelets. Platelet-derived CXCL12 also modulates paracrine mechanisms such as
      chemotaxis, adhesion, proliferation and differentiation of nucleated cells,
      including progenitor cells. Platelet-derived CXCL12 enhances peripheral
      recruitment of progenitor cells to the sites of vascular and tissue injury both
      in vitro and in vivo and thereby promotes repair mechanisms. CXCL12 expression on
      platelets is elevated in patients with acute myocardial infarction, correlates
      with the number of circulating progenitor cells, is associated with preservation
      of myocardial function and is an independent predictor of clinical outcome.
      Administration of recombinant CXCL12 reduces infarct size following transient
      ischemia in mice. The present review summarizes the role of platelet-derived
      CXCL12 in cardiovascular biology and its diagnostic and therapeutic implications.

PMID- 24024929
TI  - Metabolic system alterations in pancreatic cancer patient serum: potential for
      early detection.
AB  - BACKGROUND: The prognosis of pancreatic cancer (PC) is one of the poorest among
      all cancers, due largely to the lack of methods for screening and early
      detection. New biomarkers for identifying high-risk or early-stage subjects could
      significantly impact PC mortality. The goal of this study was to find metabolic
      biomarkers associated with PC by using a comprehensive metabolomics technology to
      compare serum profiles of PC patients to healthy control subjects. METHODS: A non
      targeted metabolomics approach based on high-resolution, flow-injection Fourier
      transform ion cyclotron resonance mass spectrometry (FI-FTICR-MS) was used to
      generate comprehensive metabolomic profiles containing 2478 accurate mass
      measurements from the serum of Japanese PC patients (n=40) and disease-free
      subjects (n=50). Targeted flow-injection tandem mass spectrometry (FI-MS/MS)
      assays for specific metabolic systems were developed and used to validate the FI
      FTICR-MS results. A FI-MS/MS assay for the most discriminating metabolite
      discovered by FI-FTICR-MS (PC-594) was further validated in two USA Caucasian
      populations; one comprised 14 PCs, six intraductal papillary mucinous neoplasms
      (IPMN) and 40 controls, and a second comprised 1000 reference subjects aged 30 to
      80, which was used to create a distribution of PC-594 levels among the general
      population. RESULTS: FI-FTICR-MS metabolomic analysis showed significant
      reductions in the serum levels of metabolites belonging to five systems in PC
      patients compared to controls (all p<0.000025). The metabolic systems included 36
      carbon ultra long-chain fatty acids, multiple choline-related systems including
      phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, as well as
      vinyl ether-containing plasmalogen ethanolamines. ROC-AUCs based on FI-MS/MS of
      selected markers from each system ranged between 0.93 +/-0.03 and 0.97 +/-0.02.
      No significant correlations between any of the systems and disease-stage, gender,
      or treatment were observed. Biomarker PC-594 (an ultra long-chain fatty acid),
      was further validated using an independently-collected US Caucasian population
      (blinded analysis, n=60, p=9.9E-14, AUC=0.97 +/-0.02). PC-594 levels across 1000
      reference subjects showed an inverse correlation with age, resulting in a drop in
      the AUC from 0.99 +/-0.01 to 0.90 +/-0.02 for subjects aged 30 to 80,
      respectively. A PC-594 test positivity rate of 5.0% in low-risk reference
      subjects resulted in a PC sensitivity of 87% and a significant improvement in net
      clinical benefit based on decision curve analysis. CONCLUSIONS: The serum
      metabolome of PC patients is significantly altered. The utility of serum
      metabolite biomarkers, particularly PC-594, for identifying subjects with
      elevated risk of PC should be further investigated.

PMID- 24024930
TI  - Genome-wide association analyses for carcass quality in crossbred beef cattle.
AB  - BACKGROUND: Genetic improvement of beef quality will benefit both producers and
      consumers, and can be achieved by selecting animals that carry desired
      quantitative trait nucleotides (QTN), which result from intensive searches using
      genetic markers. This paper presents a genome-wide association approach utilizing
      single nucleotide polymorphisms (SNP) in the Illumina BovineSNP50 BeadChip to
      seek genomic regions that potentially harbor genes or QTN underlying variation in
      carcass quality of beef cattle.This study used 747 genotyped animals, mainly
      crossbred, with phenotypes on twelve carcass quality traits, including hot
      carcass weight (HCW), back fat thickness (BF), Longissimus dorsi muscle area or
      ribeye area (REA), marbling scores (MRB), lean yield grade by Beef Improvement
      Federation formulae (BIFYLD), steak tenderness by Warner-Bratzler shear force 7
      day post-mortem (LM7D) as well as body composition as determined by partial rib
      (IMPS 103) dissection presented as a percentage of total rib weight including
      body cavity fat (BDFR), lean (LNR), bone (BNR), intermuscular fat (INFR),
      subcutaneous fat (SQFR), and total fat (TLFR). RESULTS: At the genome wide level
      false discovery rate (FDR < 10%), eight SNP were found significantly associated
      with HCW. Seven of these SNP were located on Bos taurus autosome (BTA) 6. At a
      less stringent significance level (P < 0.001), 520 SNP were found significantly
      associated with mostly individual traits (473 SNP), and multiple traits (47 SNP).
      Of these significant SNP, 48 were located on BTA6, and 22 of them were in
      association with hot carcass weight. There were 53 SNP associated with percentage
      of rib bone, and 12 of them were on BTA20. The rest of the significant SNP were
      scattered over other chromosomes. They accounted for 1.90 - 5.89% of the
      phenotypic variance of the traits. A region of approximately 4 Mbp long on BTA6
      was found to be a potential area to harbor candidate genes influencing growth.
      One marker on BTA25 accounting for 2.67% of the variation in LM7D may be worth
      further investigation for the improvement of beef tenderness. CONCLUSION: This
      study provides useful information to further assist the identification of
      chromosome regions and subsequently genes affecting carcass quality traits in
      beef cattle. It also revealed many SNP that acted pleiotropically to affect
      carcass quality. This knowledge is important in selecting subsets of SNP to
      improve the performance of beef cattle.

PMID- 24024931
TI  - Educational interventions in neurology: a comprehensive systematic review.

PMID- 24024932
TI  - Educational interventions in neurology: a comprehensive systematic review--reply
      to letter.

PMID- 24024933
TI  - Postictal psychosis in temporal lobe epilepsy.

PMID- 24024935
TI  - Hurthle cell presence alters the distribution and outcome of categories in the
      Bethesda system for reporting thyroid cytopathology.
AB  - OBJECTIVES: We aimed to determine whether the presence of Hurthle cells altered
      the distribution of categories in the Bethesda system for reporting thyroid
      cytopathology, or the expected neoplastic and malignant outcome. METHODS: Fine
      needle aspiration (FNA) cytology reports of Hurthle cells in a 2-year period were
      evaluated. The distribution of Bethesda system categories and the outcome at
      partial or complete thyroidectomy were compared for FNAs with and without Hurthle
      cells. RESULTS: Of 895 adequate FNAs with Hurthle cells, 764 (85.4%) were
      classified as benign, 86 (9.6%) as atypia of undetermined significance/follicular
      lesion of undetermined significance (AUS/FLUS), 32 (3.6%) as follicular
      neoplasm/suspicious for follicular neoplasm (FN/SFN), 12 (1.3%) as suspicious for
      malignancy (SFM) and one (0.1%) as malignant. Of 10 359 adequate FNAs without
      Hurthle cells, 9707 (93.7%) were classified as benign, 412 (4.0%) as AUS/FLUS, 77
      (0.7%) as FN/SFN, 93 (0.9%) as SFM and 70 (0.7%) as malignant. The distribution
      of categories in FNAs with and without Hurthle cells was significantly different
      (P < 0.001) as a result of a decrease in benign and an increase in AUS/FLUS and
      FN/SFN categories. Among 128 patients with and 582 without Hurthle cells
      undergoing surgery, the overall neoplastic and malignancy rates were higher in
      the former than in the latter group (27.3% versus 14.9%, P < 0.001; 21.1% versus
      11.7%, P = 0.003; respectively). Although neoplastic and malignant rates were
      higher in the group with than without Hurthle cells in all categories, the
      differences were only significant for a neoplastic outcome of benign cytology
      (15.1% versus 6.0%, P = 0.0013) and a malignant outcome of FN/SFN cytology (63.6%
      versus 21.9%, P = 0.0108). CONCLUSIONS: We found that the rates of AUS/FLUS and
      FN/SFN categories in the Bethesda system were higher when Hurthle cells were
      present. After surgery, neoplastic and malignant outcomes were significantly
      higher in the Hurthle cell group.

PMID- 24024936
TI  - Moment-independent sensitivity analysis using copula.
AB  - In risk assessment, the moment-independent sensitivity analysis (SA) technique
      for reducing the model uncertainty has attracted a great deal of attention from
      analysts and practitioners. It aims at measuring the relative importance of an
      individual input, or a set of inputs, in determining the uncertainty of model
      output by looking at the entire distribution range of model output. In this
      article, along the lines of Plischke et al., we point out that the original
      moment-independent SA index (also called delta index) can also be interpreted as
      the dependence measure between model output and input variables, and introduce
      another moment-independent SA index (called extended delta index) based on
      copula. Then, nonparametric methods for estimating the delta and extended delta
      indices are proposed. Both methods need only a set of samples to compute all the
      indices; thus, they conquer the problem of the "curse of dimensionality." At
      last, an analytical test example, a risk assessment model, and the levelE model
      are employed for comparing the delta and the extended delta indices and testing
      the two calculation methods. Results show that the delta and the extended delta
      indices produce the same importance ranking in these three test examples. It is
      also shown that these two proposed calculation methods dramatically reduce the
      computational burden. 

PMID- 24024938
TI  - Use of steady-state biofilm model to characterize aerobic granular sludge.
AB  - In this study, a steady-state biofilm model was utilized to elucidate the aerobic
      granular sludge process. In order to describe the experiment data using the
      model, two different sizes of stabilized aerobic granules (with mean diameters of
      0.6 mm and 3 mm, respectively) were investigated through the laboratory
      operations of sequencing batch reactors (SBRs). On the basis of the estimated
      parameters from experiments, the model was established to describe the biofilm
      functions in aerobic granules, such as substrate transfer and substrate
      concentration variations within the granules. In the modeling at different
      chemical oxygen demand (COD) concentrations (100-1000 mg/L), the biofilm
      functions were affected by the characteristics of aerobic granules, such as
      diameter and density. The larger granules modeled higher substrate fluxes (1.8-14
      mg/cm(2)-d) and deeper effective film thicknesses (0.18-1.3 cm). The multi-aspect
      simulation results demonstrated that the substrate either approaches zero in the
      film (at low concentration) or penetrates the granules (at high concentration).
      The sum of aerobic granules in the SBRs can be considered as a mass of biofilm,
      where the substrate approaches zero at sufficient depth. The steady-state biofilm
      model could be an effective prediction method for optimizing the aerobic granular
      sludge process. 

PMID- 24024939
TI  - Metabotropic glutamate receptor 5 in schizophrenia: emerging evidence for the
      development of antipsychotic drugs.

PMID- 24024937
TI  - Midkine in host defence.
AB  - Midkine (MK) shares several features in common with antibacterial proteins of the
      innate immune system. These include growth factor properties, heparin-binding
      regions and effects on immune cells, such as recruitment and activation of
      neutrophils and macrophages. Indeed, recent research has demonstrated potent
      bactericidal and fungicidal activities of MK. This protein is constitutively
      expressed at relevant concentrations at barriers of the body, such as the skin
      and the large airways, where the body first encounters potential pathogens. The
      antibacterial properties of MK orthologues are preserved during evolution, as
      exemplified by miple2 of Drosophila. In addition to retinoic acid, promoters of
      MK gene expression include factors present at sites of infection, reactive oxygen
      species, activation of the transcription factor NF-kappaB and hypoxia. In the
      light of the development of resistance in pathogenic bacteria to conventional
      antibiotics, MK is an interesting molecule that could serve as a template in
      developing novel therapeutic strategies against bacterial and fungal infections,
      either alone or in combination with conventional antibiotics. LINKED ARTICLES:
      This article is part of a themed section on Midkine. To view the other articles
      in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4.

PMID- 24024940
TI  - Glycine reuptake inhibition: a promising therapeutic strategy in the treatment of
      schizophrenia?

PMID- 24024942
TI  - Interview: interview with P Jeffrey Conn. Interview by Hannah Coaker.
AB  - Dr Conn is the Lee E Limbird Professor of Pharmacology at Vanderbilt University
      and Director of the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD). Dr
      Conn received a PhD in Pharmacology from Vanderbilt in 1986 and pursued
      postdoctoral studies at Yale University. He served as a professor of Pharmacology
      at Emory University from 1988 to 2000, before moving to Merck and Co. (PA, USA)
      as head of the Department of Neuroscience. Dr Conn moved to Vanderbilt University
      in 2003 where he is the founding director of the VCNDD, with a primary mission of
      facilitating translation of recent advances in basic science to novel
      therapeutics. The VCNDD consists of approximately 100 full-time scientists and
      has advanced novel molecules from four major programs as development candidates
      for clinical testing with industry partners. Dr Conn has served in editorial
      positions with multiple international journals and has served the scientific
      advisory boards of multiple foundations and companies. He has received numerous
      awards based on the impact of his basic and translational research. Dr Conn's
      current research is focused on development of novel treatment strategies for
      schizophrenia, Parkinson's disease and other serious brain disorders. Interview
      conducted by Hannah Coaker, Assistant Commissioning Editor. 

PMID- 24024943
TI  - Therapeutic potential of isoform selective HDAC inhibitors for the treatment of
      schizophrenia.
AB  - Increasing evidence supports a role for epigenetic involvement in some of the
      neurobiological alterations observed in neurodegenerative and psychiatric
      disorders including schizophrenia. In particular, there is mounting evidence
      implicating dysfunction in acetylation status, a chromatin modification mediated
      in part by HDACs, as a possible contributing factor to certain facets of this
      debilitating disease. Additional data support the notion that small molecule
      inhibition of HDACs may provide therapeutic alternatives to treating many of the
      symptoms associated with schizophrenia, particularly cognitive deficits. However,
      the development of highly potent and selective inhibitors of the individual HDAC
      isoforms will be necessary to delineate the associated biological effects and
      test the feasibility of such an approach for this complex and chronically treated
      disease. Here, we summarize current evidence for the role of HDAC isoforms in
      schizophrenia and highlight the state of the art in developing selective
      inhibitors of these isoforms as a potential treatment for schizophrenia. 

PMID- 24024944
TI  - Peptide POP inhibitors for the treatment of the cognitive symptoms of
      schizophrenia.
AB  - Schizophrenia is a serious life-long disease that affects a significant part of
      the adult population. Although there is considerably effective medication for the
      positive symptoms of the disease, none are available for the associated cognitive
      deficits. These deficits are a core feature of schizophrenia, and they severely
      impair the functionality and social integration of patients. POP is a promising
      target for the treatment of the cognitive deficits of schizophrenia. Inhibitors
      of this peptidase show cognition-enhancing properties, act through a complex
      mechanism and have suitable pharmacological properties. Nevertheless, several
      studies must be carried out in order to improve the design and clinical
      evaluation of these substances. Permeability to the brain, appropriate animal
      models and suitable indications are the main issues that must be addressed.
      However, current information supports the potential of POP as an interesting drug
      target for the treatment of the cognitive deficits related to schizophrenia. 

PMID- 24024945
TI  - Progress in the development of neurokinin 3 modulators for the treatment of
      schizophrenia: molecule development and clinical progress.
AB  - The neuropeptide NK3 receptor is expressed almost exclusively within the
      mammalian nervous system and its localization is commensurate with a role in
      modulating central monoaminergic neurotransmission. Following on from our
      previous work we review the rationale for NK3 receptor antagonists as wide
      spectrum antipsychotics and the recent scientific and patent literature that has
      highlighted new chemical strategies to identify selective NK3 and dual activity
      NK1/3 receptor ligands for the putative treatment of schizophrenia. We discuss
      the emerging structural biology and its use in the design of molecules with
      increased structural diversity and predictable receptor pharmacology. Particular
      attention is paid to the progress in improving ligand drug-like properties. The
      status of imaging and the development of translational technologies in the
      neurokinin field are also discussed. Finally, we summarize the available clinical
      information on the compounds that have progressed into psychiatric patient
      populations and evaluate the potential therapeutic utility of NK3 receptor
      targeted ligands. 

PMID- 24024946
TI  - Cholinergic muscarinic receptors: new opportunities to treat psychiatric
      disorders.

PMID- 24024947
TI  - Candidate molecules for chemical chaperone therapy of GM1-gangliosidosis.
AB  - A growing body of evidence suggests that misfolding of a mutant protein followed
      by its aggregation or premature degradation in the endoplasmic reticulum is one
      of the main mechanisms that underlie inherited neurodegenerative diseases,
      including lysosomal storage diseases. Chemical or pharmacological chaperones are
      small molecules that bind to and stabilize mutant lysosomal enzyme proteins in
      the endoplasmic reticulum. A number of chaperone compounds for lysosomal
      hydrolases have been identified in the last decade. They have gained attention
      because they can be orally administrated, and also because they can penetrate the
      blood-brain barrier. In this article, we describe two chaperone candidates for
      the treatment of GM1-gangliosidosis. We also discuss the future direction of this
      strategy targeting other lysosomal storage diseases as well as protein misfolding
      diseases in general. 

PMID- 24024948
TI  - Anti-neuroinflammatory agents for the treatment of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is complicated and difficult to fully understand, it
      might need multiple drug-discovery strategies to combat the disease. Regardless
      of the cause of AD, neuronal death in the brain plays a key role in AD
      progression and is directly linked to neuroinflammation. Thus, the regulation of
      neuroinflammatory processes might be a practical strategy for the treatment of
      AD. This review highlights the development of anti-neuroinflammatory agents that
      have shown promise in vitro or in vivo by attenuating microglial activation or
      cognitive decline. The agents are categorized based on the related signaling
      pathways, including the receptor for advanced glycation end products, p38 MAPKs,
      NF-kappaB and peroxisome proliferator-activated receptor gamma; and inhibitors
      against microglial activation lacking clear mechanisms. These anti
      neuroinflammatory agents support the concept and represent important chemical
      probes for the development of anti-neuroinflammatory drugs for the treatment of
      AD. 

PMID- 24024949
TI  - Targeting the mitochondrial electron transport chain of Plasmodium falciparum:
      new strategies towards the development of improved antimalarials for the
      elimination era.
AB  - Despite intense efforts, there has not been a truly new antimalarial, possessing
      a novel mechanism of action, registered for over 10 years. By virtue of a novel
      mode of action, it is hoped that the global challenge of multidrug-resistant
      parasites can be overcome, as well as developing drugs that possess prophylaxis
      and/or transmission-blocking properties, towards an elimination agenda. Many
      target-based and whole-cell screening drug development programs have been
      undertaken in recent years and here an overview of specific projects that have
      focused on targeting the parasite's mitochondrial electron transport chain is
      presented. Medicinal chemistry activity has largely focused on inhibitors of the
      parasite cytochrome bc1 Complex (Complex III) including acridinediones, pyridones
      and quinolone aryl esters, as well as inhibitors of dihydroorotate dehydrogenase
      that includes triazolopyrimidines and benzimidazoles. Common barriers to progress
      and opportunities for novel chemistry and potential additional electron transport
      chain targets are discussed in the context of the target candidate profiles for
      uncomplicated malaria. 

PMID- 24024951
TI  - Optimizing experimental design using the house mouse (Mus musculus L.) as a model
      for determining grain feeding preferences.
AB  - There is little research evaluating flavor preferences among wheat varieties. We
      previously demonstrated that mice exert very strong preferences when given binary
      mixtures of wheat varieties. We plan to utilize mice to identify wheat genes
      associated with flavor, and then relate this back to human preferences. Here we
      explore the effects of experimental design including the number of days (from 1
      to 4) and number of mice (from 2 to 15) in order to identify designs that provide
      significant statistical inferences while minimizing requirements for labor and
      animals. When mice expressed a significant preference between 2 wheat varieties,
      increasing the number of days (for a given number of mice) increased the
      significance level (decreased P-values) for their preference, as expected, but
      with diminishing benefit as more days were added. However, increasing the number
      of mice (for a given number of days) provided a more dramatic log-linear decrease
      in P-values and thus increased statistical power. In conclusion, when evaluating
      mouse feeding preferences in binary mixtures of grain, an efficient experimental
      design would emphasize fewer days rather than fewer animals thus shortening the
      experiment duration and reducing the overall requirement for labor and animals. 

PMID- 24024952
TI  - Role of ascorbic acid in counteracting ferric nitrilotriacetate-induced
      nephrotoxicity in rats.
AB  - CONTEXT: Ascorbic acid (AA) is a naturally occurring organic compound with
      antioxidant properties. It is necessary for normal growth and development, and
      has been shown to protect against tissue toxicity and oxidative stress.
      OBJECTIVE: The protective effect of AA against nephrotoxicity induced in albino
      rats by ferric nitrilotriacetate (Fe-NTA) was evaluated. MATERIALS AND METHODS:
      Male albino rats of Wistar strain (4-6 weeks old) weighing 125-150 g were used in
      this study. Animals were given a single dose of Fe-NTA (9 mg/kg body weight,
      intraperitoneal) after a week of treatment with AA (1 and 2 mg/animal/day).
      RESULTS: Fe-NTA treatment enhanced microsomal lipid peroxidation (LPO) and
      hydrogen peroxide (H2O2) generation to 1.7- to 2.2-fold, glutathione (GSH) levels
      were decreased by two-fold and the activities of GSH metabolizing enzymes
      decreased to a range of 2.2- to 2.5-fold in renal tissue. These changes were
      reversed significantly in animals receiving pretreatment of AA. Treatment of rats
      with AA prior to the treatment with Fe-NTA decreased microsomal LPO and H2O2
      generation to 124 and 172%, and also resulted in the recovery of reduced levels
      of GSH, GSH-metabolizing enzymes to almost 92% at the higher dose level of AA.
      DISCUSSION AND CONCLUSION: AA protects against Fe-NTA-induced nephrotoxicity and
      renal damage. AA has a beneficial impact on Fe-NTA-induced toxicity due to its
      scavenging and antioxidant effect in albino rats.

PMID- 24024953
TI  - Temperature-activated nucleic acid nanostructures.
AB  - DNA and poly(N-isopropylacrylamide) are co-assembled onto gold nanoparticles. The
      DNA sequences can be reversibly exposed or hidden from the polymer surface in
      response to temperature cues, thereby translating the temperature trigger to the
      on-off switching of the surface chemistry and function. When exposed by heating
      (~30  degrees C), the DNA rapidly hybridizes to complementary strands, and chain
      end biotin groups become readily accessible, while at lower temperatures these
      activities are largely blocked. 

PMID- 24024954
TI  - Developmental cycle and host interaction of Rhabdochlamydia porcellionis, an
      intracellular parasite of terrestrial isopods.
AB  - Environmental chlamydiae are a diverse group of obligate intracellular bacteria
      related to well-known pathogens of humans. To date, only very little is known
      about chlamydial species infecting arthropods. In this study, we used
      cocultivation with insect cells for recovery and maintenance of Rhabdochlamydia
      porcellionis, a parasite of the crustacean host Porcellio scaber. In vitro, the
      infection cycle of R. porcellionis was completed within 7 days, resulting in the
      release of infectious particles by host cell lysis. Lack of apoptosis induction
      during the entire course of infection, combined with a reduced sensitivity of
      infected cultures to experimentally induced programmed cell death, indicates that
      R. porcellionis like its human pathogenic relatives counteracts this host defence
      mechanism. Interestingly, the rod-shaped variant of R. porcellionis, proposed to
      represent their mature infective stage, was not detected in cell culture,
      suggesting that its development may require prolonged maturation or may be
      triggered by specific conditions encountered only in the animal host. This first
      cell culture-based system for the cultivation and investigation of an arthropod
      associated chlamydial species will help to better understand the biology of a so
      far neglected group of chlamydiae and its recently suggested potential to cause
      disease in humans. 

PMID- 24024955
TI  - Speech and phonology in Swedish-speaking 3-year-olds with unilateral complete
      cleft lip and palate following different methods for primary palatal surgery.
AB  - Objective : To describe and compare speech and phonology at age 3 years in
      children born with unilateral complete cleft lip and palate treated with three
      different methods for primary palatal surgery. Design : Prospective study.
      Setting : Primary care university hospitals. Participants : Twenty-eight Swedish
      speaking children born with nonsyndromic unilateral complete cleft lip and
      palate. Interventions : Three methods for primary palatal surgery: two-stage
      closure with soft palate closure between 3.4 and 6.4 months and hard palate
      closure at mean age 12.3 months (n = 9) or 36.2 months (n = 9) or one-stage
      closure at mean age 13.6 months (n = 10). Main Outcome Measures : Based on
      independent judgments performed by two speech-language pathologists from
      standardized video recordings: percent correct consonants adjusted for age,
      percent active cleft speech characteristics, total number of phonological
      processes, number of different phonological processes, hypernasality, and audible
      nasal air leakage. The hard palate was unrepaired in nine of the children treated
      with two-stage closure. Results : The group treated with one-stage closure showed
      significantly better results than the group with an unoperated hard palate
      regarding percent active cleft speech characteristics and total number of
      phonological processes. Conclusions : Early primary palatal surgery in one or two
      stages did not result in any significant differences in speech production at age
      3 years. However, children with an unoperated hard palate had significantly
      poorer speech and phonology than peers who had been treated with one-stage
      palatal closure at about 13 months of age. 

PMID- 24024956
TI  - Simultaneous alveolar cleft closure and dental midline correction with
      curvilinear intraoral distraction.
AB  - This article describes a new method that enables vector control during alveolar
      distraction osteogenesis in the treatment of a cleft palate patient. The patient
      presented with unilateral complete cleft lip and palate, and the alveolar part of
      the defect was covered by a mobile buccal flap. The distraction was performed by
      sliding the surgically released tooth segment with the help of an intraoral
      distractor over 1.5-mm stainless steel archwires held by metal crowns. This
      vector-controlled method enabled new bone and attached gingiva formation in
      harmony with the proper alveolar shape. 

PMID- 24024957
TI  - Impact of maxillary advancement on speech and velopharyngeal function in patients
      with cleft lip and palate.
AB  - Objective : Patients with cleft lip and palate (CLP) and maxillary retrognathia
      are usually treated with maxillary advancement (Le Fort I osteotomy). The aim of
      this study was to investigate the impact of maxillary advancement on the
      velopharyngeal function (VPF) and symptoms of velopharyngeal incompetence in
      patients with CLP. Design : Retrospective group study before and after treatment.
      Participants : All patients who had undergone Le Fort I osteotomy due to
      maxillary retrognathia from 2007 to 2010 at Karolinska University Hospital,
      Sweden (n = 13). Pre- and postoperatively standardized examinations were used.
      Blinded audio recordings were independently assessed by three experienced speech
      pathologists. Acoustical data (nasometry) and information on VPF
      (videoradiography and nasoendoscopy) were collected from the medical records. Two
      patients with additional malformations were considered outliers, and group data
      were based on a sample size of n = 11. Main Outcome Measures : Perceptual and
      acoustic symptoms of velopharyngeal incompetence and overall assessment of VPF.
      Results : No assessment method showed a significant deterioration of the VPF
      postoperatively. Individual data revealed that 6 of the 13 patients had no or
      only one symptom pre- and/or postoperatively. The two patients with additional
      malformations had most symptoms pre- and postoperatively and did not change.
      Three patients had an increased number of symptoms postoperatively by at least
      two symptoms. No associations between the outcome and possible prognostic factors
      were found. Conclusions : Maxillary advancement did not have a significant impact
      on the VPF at the group level, but three individuals had a somewhat deteriorated
      VPF postoperatively. 

PMID- 24024958
TI  - Surgical strategy and results of treatment for dumbbell-shaped spinal neurinoma
      with a posterior approach.
AB  - OBJECTIVE: Total removal of neurinomas is generally an achievable goal that
      yields good results; however, dumbbell-shaped neurinomas often present challenges
      for complete resection. Some extensive surgical approaches for complete removal
      have been reported to lead to severe complications. Therefore, the surgical
      strategy for dumbbell-shaped neurinomas is controversial. METHODS: Twelve
      patients with dumbbell-shaped neurinomas were surgically treated in our hospital
      over 5 years. We adopted a posterior approach to remove the intracanalicular
      portion of the neurinomas as completely as possible, intentionally leaving the
      foraminal portion unresected to prevent bony and vascular insult. We investigated
      the postoperative surgical results and complications and the regrowth rate of the
      remnant lesions. RESULTS: Postoperative residual tumours were identified in 6 of
      the 12 patients. The perioperative neurological findings between the two groups
      were almost the same. The recurrence rate was low. Severe surgery-related
      complications occurred in only one patient with mild and temporary motor
      weakness. CONCLUSION: Our strategy demonstrated low rates of recurrence and
      complications compared with those accompanying the extensive alternative
      approaches that have been reported previously. Our case series showed that
      subtotal removal of dumbbell-shaped neurinomas using a posterior approach is a
      safer, more effective, and more minimally invasive treatment.

PMID- 24024959
TI  - MnO2 promoted sequential C-O and C-N bond formation via C-H activation of
      methylarenes: a new approach to amides.
AB  - A novel and efficient approach for the synthesis of amides has been developed
      through manganese dioxide promoted nondirected C-H activation of methylarenes
      under mild reaction conditions employing N-chloroamines as effective coupling
      partners. 

PMID- 24024960
TI  - Mapping hotspots of threatened species traded in bushmeat markets in the Cross
      Sanaga rivers region.
AB  - Bushmeat markets exist in many countries in West and Central Africa, and data on
      species sold can be used to detect patterns of wildlife trade in a region. We
      surveyed 89 markets within the Cross-Sanaga rivers region, West Africa. In each
      market, we counted the number of carcasses of each taxon sold. During a 6-month
      period (7594 market days), 44 mammal species were traded. Thirteen species were
      on the International Union for Conservation of Nature (IUCN) Red List or
      protected under national legislation, and at least 1 threatened species was
      traded in 88 of the 89 markets. We used these data to identify market groups that
      traded similar species assemblages. Using cluster analyses, we detected 8 market
      groups that were also geographically distinct. Market groups differed in the
      diversity of species, evenness of species, and dominant, prevalent, and
      characteristic species traded. We mapped the distribution of number of threatened
      species traded across the study region. Most threatened species were sold in
      markets nearest 2 national parks, Korup National Park in Cameroon and Cross River
      in Nigeria. To assess whether the threatened-species trade hotspots coincided
      with the known ranges of these species, we mapped the overlap of all threatened
      species traded. Markets selling more threatened species overlapped with those
      regions that had higher numbers of these. Our study can provide wildlife managers
      in the region with better tools to discern zones within which to focus policing
      efforts and reduce threats to species that are threatened by the bushmeat trade.

PMID- 24024961
TI  - Ring expansions of vinyloxiranes, -thiiranes, and -aziridines: synthetic
      approaches, challenges, and catalytic success stories.
AB  - Ring expansion reactions of strained vinylic heterocyclic substrates have
      attracted the attention of the synthetic community for decades. Strategic
      manipulations of these organic architectures enable access to many useful
      synthetic intermediates. This paper highlights various methods for the ring
      expansion of vinyloxiranes, -thiiranes, and -aziridines described in the
      literature from 1964 to 2013. 

PMID- 24024962
TI  - Predictors of in-hospital death and symptomatic intracranial hemorrhage in
      patients with acute ischemic stroke treated with thrombolytic therapy: Paul
      Coverdell Acute Stroke Registry 2008-2012.
AB  - BACKGROUND: Limited studies exist on the outcome of thrombolytic therapy of acute
      ischemic stroke patients outside of clinical trials. AIM: To assess the possible
      risk factors associated with in-hospital death and symptomatic intracerebral
      hemorrhage among patients who received intravenous tissue plasminogen activator.
      METHODS: A total of 7193 patients with a clinical diagnosis of acute ischemic
      stroke and a documented National Institutes of Health Stroke Scale score were
      treated with intravenous tissue plasminogen activator within 4.5 hours of time
      last known to be well. Generalized estimating equations modeling was used to
      assess the associations of in-hospital death and symptomatic intracerebral
      hemorrhage with clinical characteristics. RESULTS: Among 7193 patients treated
      with intravenous tissue plasminogen activator, 516 (7.2%) died during
      hospitalization. Factors associated with in-hospital death were older age, male
      gender, National Institutes of Health Stroke Scale score, history of myocardial
      infarction or coronary artery disease, and history of nonvalvular atrial
      fibrillation. Increasing age, higher National Institutes of Health Stroke Scale
      score, and history of dyslipidemia were associated with symptomatic intracerebral
      hemorrhage. There was no difference in the rates of in-hospital death or
      symptomatic intracerebral hemorrhage among patients treated with intravenous
      tissue plasminogen activator within three-hours of time last known to be well and
      those treated between three and 4.5 hours after this time. CONCLUSIONS: In this
      study of acute ischemic stroke patients, older age, male gender, National
      Institutes of Health Stroke Scale score, history of myocardial infarction or
      coronary artery disease, and history of atrial fibrillation were associated with
      increased in-hospital death among patients receiving intravenous tissue
      plasminogen activator. Among patients treated with intravenous tissue plasminogen
      activator, in-hospital mortality and symptomatic intracerebral hemorrhage rates
      were similar between those treated within three-hours of time last known to be
      well and those treated between three and 4.5 hours after this time.

PMID- 24024964
TI  - Long-circulating heparin-functionalized magnetic nanoparticles for potential
      application as a protein drug delivery platform.
AB  - Starch-coated, PEGylated, and heparin-functionalized iron oxide magnetic
      nanoparticles (DNPH) were successfully synthesized and characterized in detail.
      The PEGylation (20 kDa) process resulted in an average coating of 430 PEG
      molecules per nanoparticle. After that, heparin conjugation was carried out to
      attain the final DNPH platform with 35.4 MUg of heparin/mg of Fe. Commercially
      acquired heparin-coated magnetic nanoparticles were also PEGylated (HP) and
      characterized for comparison. Protamine was selected as a model protein to
      demonstrate the strong binding affinity and high loading content of DNPH for
      therapeutically relevant cationic proteins. DNPH showed a maximum loading of 22.9
      MUg of protamine/mg of Fe. In the pharmacokinetic study, DNPH displayed a long
      circulating half-life of 9.37 h, 37.5-fold longer than that (0.15 h) of HP. This
      improved plasma stability enabled extended exposure of DNPH to the tumor lesions,
      as was visually confirmed in a flank 9L-glioma mouse model using magnetic
      resonance imaging (MRI). Quantitative analysis of the Fe content in excised tumor
      lesions further demonstrated the superior tumor targeting ability of DNPH, with
      up to 31.36 MUg of Fe/g of tissue (13.07% injected dose (I.D.)/g of tissue) and
      7.5-fold improvement over that (4.27 MUg of Fe/g of tissue; 1.78% I.D./g of
      tissue) of HP. Overall, this study shed light on the potential of DNPH to be used
      as a protein drug delivery platform. 

PMID- 24024965
TI  - The concept of "confirmatory testing" of donors for ABO and RhD.

PMID- 24024963
TI  - Genome-wide association study of shared components of reading disability and
      language impairment.
AB  - Written and verbal languages are neurobehavioral traits vital to the development
      of communication skills. Unfortunately, disorders involving these traits
      specifically reading disability (RD) and language impairment (LI)-are common and
      prevent affected individuals from developing adequate communication skills,
      leaving them at risk for adverse academic, socioeconomic and psychiatric
      outcomes. Both RD and LI are complex traits that frequently co-occur, leading us
      to hypothesize that these disorders share genetic etiologies. To test this, we
      performed a genome-wide association study on individuals affected with both RD
      and LI in the Avon Longitudinal Study of Parents and Children. The strongest
      associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 * 10(-7) )
      and COL4A2 (OR = 1.71, P = 7.59 * 10(-7) ). Markers within NDST4 showed the
      strongest associations with LI individually (OR = 1.827, P = 1.40 * 10(-7) ). We
      replicated association of ZNF385D using receptive vocabulary measures in the
      Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used
      diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine
      the implications of replicated markers. ZNF385D was a predictor of overall fiber
      tract volumes in both hemispheres, as well as global brain volume. Here, we
      present evidence for ZNF385D as a candidate gene for RD and LI. The implication
      of transcription factor ZNF385D in RD and LI underscores the importance of
      transcriptional regulation in the development of higher order neurocognitive
      traits. Further study is necessary to discern target genes of ZNF385D and how it
      functions within neural development of fluent language.

PMID- 24024966
TI  - Genome-wide association study of chronic periodontitis in a general German
      population.
AB  - AIM: To identify loci associated with chronic periodontitis through a genome-wide
      association study (GWAS). MATERIALS AND METHODS: A GWAS was performed in 4032
      individuals of two independent cross-sectional studies of West Pomerania (SHIP n
      = 3365 and SHIP-TREND n = 667) with different periodontal case definitions.
      Samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 6.0 or the
      Illumina Human Omni 2.5 array. Imputation of the HapMap as well as the 1000
      Genome-based autosomal and X-chromosomal genotypes and short insertions and
      deletions (INDELs) was performed in both cohorts. Finally, more than 17 million
      SNPs and short INDELs were analysed. RESULTS: No genome-wide significant
      associations were found for any periodontitis case definition, regardless of
      whether individuals aged >60 years where excluded or not. Despite no single SNP
      association reached genome-wide significance, the proportion of variance
      explained by additive effects of all common SNPs was around 23% for mean proximal
      attachment loss. Excluding subjects aged >60 years increased the explained
      variance to 34%. CONCLUSIONS: No single SNPs were found to be genome-wide
      significantly associated with chronic periodontitis in this study.

PMID- 24024967
TI  - Blood transfusion; additional historical aspects. Part 2. The introduction of
      chemical anticoagulants; trials of 'Phosphate of soda'.
AB  - The pioneers of transfusion medicine around the turn of the 19th into the 20th
      centuries struggled with the awkward propensity of shed blood to clot. This
      article, a companion to a previous one (Boulton, 2013, Submitted for
      publication), describes in more detail how they recognised a potential for
      chemical anticoagulants which led to the introduction for a short period of
      sodium phosphate to aid blood transfusion: these cases preceded the introduction
      of citrate (Mollison, 2000, British Journal of Haematology, 108, 13-18). 

PMID- 24024968
TI  - Agonist pharmacology at recombinant alpha1A - and alpha1L -adrenoceptors and in
      lower urinary tract alpha1 -adrenoceptors.
AB  - BACKGROUND AND PURPOSE: Two distinct alpha1 -adrenoceptor phenotypes (alpha1A and
      alpha1L ) have recently been demonstrated to originate from a single alpha1A 
      adrenoceptor gene. Here, we examined the agonist profiles of recombinant alpha1A
      and alpha1L phenotypes and of lower urinary tract (LUT) alpha1 -adrenoceptors.
      EXPERIMENTAL APPROACH: A series of drugs (A61603, Ro 115-1240, NS-49 , MK017 and
      ESR1150) originally developed for stress urinary incontinence (SUI) therapy were
      used to stimulate recombinant alpha1A - and alpha1L -adrenoceptor phenotypes, and
      their potencies and intrinsic activity estimated from Ca(2+) responses. Agonist
      induced contractions were also examined in LUT tissues of rats and humans and in
      human mesenteric artery and rat tail artery. KEY RESULTS: All the drugs were
      potent agonists of the alpha1A -adrenoceptor compared with the alpha1L 
      adrenoceptor phenotype. Among them, Ro 115-1240 was shown to be an alpha1A 
      specific partial agonist that produced partial contractions through alpha1A 
      adrenoceptors in rat prostate and tail artery, but not in the other LUT tissues
      and human mesenteric artery. In contrast, P-come 102 showed full agonist activity
      at alpha1A - and alpha1L -adrenoceptors, but was less selective than
      noradrenaline for alpha1A -adrenoceptors. Like noradrenaline, P-come 102 was
      highly potent at inducing contractions in all of the LUT tissues tested. However,
      the potency and intrinsic activity of P-come 102 were significantly lower than
      those of noradrenaline in human mesenteric artery. CONCLUSIONS AND IMPLICATIONS:
      The alpha1A - and alpha1L -adrenoceptor phenotypes and LUT alpha1 -adrenoceptors
      were demonstrated to have distinct agonist profiles. As adrenergic contractions
      in LUT are predominantly mediated through alpha1L -adrenoceptors, the development
      of alpha1L -selective agonists may provide clinically useful drugs for SUI
      therapy.

PMID- 24024971
TI  - Species-specific quantification of probiotic lactobacilli in yoghurt by
      quantitative real-time PCR.
AB  - AIMS: Lactobacilli strains with probiotic effects have been widely used in dairy
      products such as yoghurts as well as in food additives and pharmaceuticals.
      Despite their successful commercial application, the current species
      identification and quantification methods of the genus Lactobacillus are time
      consuming and labour-intensive. METHODS AND RESULTS: To fulfil the requirements
      of a robust quality management, we have developed a quantitative real-time PCR
      assay based on the heat shock protein 60 gene (hsp60) for accurate identification
      and quantification of five commercially important Lactobacillus species. The
      developed assay allows an unambiguous species-specific detection of the species
      Lact. acidophilus, Lact. brevis, Lact. delbrueckii subsp. bulgaricus, Lact.
      helveticus and Lact. reuteri from bacterial cultures as well as directly from
      dairy products for instance yoghurt. CONCLUSIONS: With the assay, we were able to
      specifically detect lactobacilli strains down to 10(5)  CFU ml(-1) directly from
      yoghurt, which is a sufficient detection limit as commercial products usually
      contain 10(6) -10(12)  CFU ml(-1) of probiotic strains. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The real-time PCR assay developed here might become a convenient
      tool enabling an accurate, fast and sensitive detection of probiotic lactobacilli
      commercially used in food.

PMID- 24024970
TI  - Factors associated with asthma among under-fives in Mulago hospital, Kampala
      Uganda: a cross sectional study.
AB  - BACKGROUND: Asthma is the most common chronic childhood illness, with rapidly
      increasing prevalence in low-income countries. Among young children, asthma is
      often under-diagnosed.We investigated the factors associated with asthma among
      under-fives presenting with acute respiratory symptoms at Mulago hospital,
      Uganda. METHODS: A hospital-based cross sectional study of 614 children with
      cough and/or difficult breathing, and fast breathing, was conducted between
      August 2011 and June 2012. A questionnaire focusing on clinical history of the
      child was administered to the caretakers. A physical examination and, laboratory
      and radiological investigations were done. Asthma was defined according to GINA
      (Global Initiative for Asthma) guidelines which were modified by excluding the
      symptom of "chest tightness", spirometry/peak expiratory flow measurements and by
      adding chest x-ray findings to distinguish asthma from pneumonia. A panel of
      three paediatricians reviewed the participants' case reports and, guided by the
      study definitions, made a diagnosis of asthma or other. Multivariable logistic
      regression analysis was done to determine factors independently associated with
      asthma. RESULTS: Of the 614 children, 128 (20.8%) had asthma, 125 (20.4%)
      bronchiolitis, 167 (27.2%) bacterial pneumonia only, 163 (26.5%) viral pneumonia
      while 31 (5.1%) had other diagnoses including pulmonary tuberculosis. The
      majority (71.1%) of children with asthma were aged >= 12 months. Factors
      associated with asthma included maternal asthma (AOR 2.4, 95% CI 1.2, 4.6), a
      history of allergy in the patient (AOR 2.6, 95% CI 1.2, 5.4,), use of gas for
      cooking (AOR 3.8, 95% CI 1.2, 13.3), prematurity (AOR 9.3, 95% CI 1.2, 83.3) and
      high level of education of caretaker (AOR 9.1, 95% CI 1.1, 72.8). CONCLUSION:
      Maternal asthma, a history of allergy in the patient, use of gas for cooking,
      prematurity and high level of education of caretaker were significantly
      associated with asthma. There is need for studies to explore the role of the
      above factors in development and exacerbation of childhood asthma to provide
      information that can be used to design strategies for asthma prevention and
      control.

PMID- 24024969
TI  - Transcriptomic characterization of cold acclimation in larval zebrafish.
AB  - BACKGROUND: Temperature is one of key environmental parameters that affect the
      whole life of fishes and an increasing number of studies have been directed
      towards understanding the mechanisms of cold acclimation in fish. However, the
      adaptation of larvae to cold stress and the cold-specific transcriptional
      alterations in fish larvae remain largely unknown. In this study, we
      characterized the development of cold-tolerance in zebrafish larvae and
      investigated the transcriptional profiles under cold stress using RNA-seq.
      RESULTS: Pre-exposure of 96 hpf zebrafish larvae to cold stress (16 degrees C)
      for 24 h significantly increased their survival rates under severe cold stress
      (12 degrees C). RNA-seq generated 272 million raw reads from six sequencing
      libraries and about 92% of the processed reads were mapped to the reference
      genome of zebrafish. Differential expression analysis identified 1,431 up- and
      399 down-regulated genes. Gene ontology enrichment analysis of cold-induced genes
      revealed that RNA splicing, ribosome biogenesis and protein catabolic process
      were the most highly overrepresented biological processes. Spliceosome,
      proteasome, eukaryotic ribosome biogenesis and RNA transport were the most highly
      enriched pathways for genes up-regulated by cold stress. Moreover, alternative
      splicing of 197 genes and promoter switching of 64 genes were found to be
      regulated by cold stress. A shorter isoform of stk16 that lacks 67 amino acids at
      the N-terminus was specifically generated by skipping the second exon in cold
      treated larvae. Alternative promoter usage was detected for per3 gene under cold
      stress, which leading to a highly up-regulated transcript encoding a truncated
      protein lacking the C-terminal domains. CONCLUSIONS: These findings indicate that
      zebrafish larvae possess the ability to build cold-tolerance under mild low
      temperature and transcriptional and post-transcriptional regulations are
      extensively involved in this acclimation process.

PMID- 24024972
TI  - Migration and opportunistic feeding increase PCB accumulation in Arctic seabirds.
AB  - It is widely accepted that body concentrations of persistent organic pollutants
      (POPs) tend to increase with trophic level (TL). Yet, little attention has been
      paid to the causes in the underlying differences in POP body concentrations
      between species occupying similar TLs. In this paper we use two modeling
      approaches to quantify the importance of migration and opportunistic feeding,
      relative to that of trophic level, in explaining interspecific differences in
      polychlorinated biphenyl (PCB) body concentrations between 6 Arctic seabird
      species breeding in the Barents Sea: Little Auk (Alle alle), Black Guillemot
      (Cepphus grylle), Brunnich's Guillemot (Uria lomvia), Common Eider (Somateria
      mollissima), Black-legged Kittiwake (Rissa tridactyla), and Glaucous Gull (Larus
      hyperboreus). As a first approach, we use additive models to analyze two
      independent data sets (n = 470 and n = 726). We demonstrate that migration,
      opportunistic feeding, and TL significantly (p < 0.001) increase PCB body
      concentrations by a factor 3.61-4.10, 2.66-20.95, and 2.38-2.41, respectively.
      Our second approach, using a mechanistic bioaccumulation model, confirmed these
      positive effects on the body burdens but suggested lower effects of migration,
      opportunistic feeding, and TL (1.55, 2.39, and 2.38) than did our statistical
      analysis. These two independent approaches demonstrate that the effects of
      migration and opportunistic feeding on seabird body burdens can be similar to
      that of an increase of one TL and should therefore be accounted for in future
      analyses. 

PMID- 24024973
TI  - Enantiomeric atropisomers inhibit HCV polymerase and/or HIV matrix:
      characterizing hindered bond rotations and target selectivity.
AB  - An anthranilic acid series of allosteric thumb pocket 2 HCV NS5B polymerase
      inhibitors exhibited hindered rotation along a covalent bond axis, and the
      existence of atropisomer chirality was confirmed by NMR, HPLC analysis on chiral
      supports, and computational studies. A thorough understanding of the concerted
      rotational properties and the influence exerted by substituents involved in this
      steric phenomenon was attained through biophysical studies on a series of
      truncated analogues. The racemization half-life of a compound within this series
      was determined to be 69 min, which was consistent with a class 2 atropisomer
      (intermediate conformational exchange). It was further found by X-ray
      crystallography that one enantiomer of a compound bound to the intended HCV NS5B
      polymerase target whereas the mirror image atropisomer was able to bind to an
      unrelated HIV matrix target. Analogues were then identified that selectively
      inhibited the former. These studies highlight that atropisomer chirality can lead
      to distinct entities with specific properties, and the phenomenon of
      atropisomerism in drug discovery should be evaluated and appropriately managed. 

PMID- 24024974
TI  - Cytotoxic, antioxidant and antimicrobial effects of nine species of woundwort
      (Stachys) plants.
AB  - CONTEXT: Woundwort (Stachys) plants from the Lamiaceae family have been used in
      folk medicine for various purposes. OBJECTIVE: This study was designed to analyze
      cytotoxic, antioxidant and antimicrobial activities of Stachys plants, because
      these fields have extensively benefited of drug discovery from natural sources.
      MATERIALS AND METHODS: Nine Stachys plants were collected from different regions
      of Iran. Cytotoxic activities of methanol, 80% methanol and dichloromethane (DCM)
      extracts of these plants were assessed on three human cancer cell lines (HL-60,
      K562 and MCF-7 cells) with the MTT assay, while antioxidant and antimicrobial
      activities were determined on methanol extracts by DPPH and nutrient broth micro
      dilution assays, respectively. RESULTS: DCM extract of St. pilifera Benth. had
      the lowest IC50 in three cancer cell lines ranging from 33.1 to 48.2 ug/ml,
      followed by the 80% methanol extract of St. persica S.G.Gmel. ex C.A.Mey. (IC50
      range: 62.1-104.1 ug/ml) and DCM extract of St. byzantina C. Koch (IC50 range:
      62.7-131.0 ug/ml). St. byzantina. St. lavandulifolia Vahl., St. acerosa Boiss.,
      St. obtusicrena Boiss. and St. persica showed lowest IC50 values in the DPPH
      scavenging assay (135.1, 162.6, 164.7, 169.4 and 172.4 ug/ml, respectively),
      while their total phenolic contents were 23.9, 18.2, 18.6, 20.4, 27.8 mg
      equivalent of gallic acid in 1 g dry plant, respectively. The methanol extracts
      of St. byzantina and St. persica inhibited all six tested Gram-negative and Gram
      positive bacterial strains. CONCLUSION: Various Stachys species (especially St.
      byzantina and St. persica) are valuable sources of natural compounds with
      important biological properties.

PMID- 24024976
TI  - [Abstracts of the Annual Meeting of the North German Dermatologic Society. August
      30-September 1, 2013. Rostock/Warnemunde, Germany].

PMID- 24024975
TI  - Physicochemical characterization and sensory analysis of yeast-leavened and
      sourdough soy breads.
AB  - Sourdough fermentation has been shown to have numerous beneficial effects on
      bread quality, and nutritionally enhance soy-supplemented bread by altering
      isoflavone chemical forms. Given this, the objective of this study was to compare
      the loaf quality and shelf life of sourdough and yeast-leavened soy breads by
      various physical, thermal, and sensorial methods, and to assess the effects of
      fermentation by various microorganisms on isoflavone profile in dough and breads
      using high-performance liquid chromatography analysis. Sourdough fermentation
      yielded a less extensible dough compared to yeast-leavened soy dough (P < 0.001),
      and resulted in a harder bread crumb (P < 0.05) and lighter crust color (P <
      0.001), compared to yeast-leavened soy bread (Y-B). Sensory analysis revealed a
      significantly higher overall liking of Y-B compared to sourdough soy bread (SD-B)
      (P < 0.001). Segmentation analysis of the cohort suggests that overall liking and
      bread consumption frequency may be determinants of Y-B or SD-B preference. SD-B
      and Y-B exhibited similar shelf-life properties. Despite significantly different
      enthalpies associated with the melting of amylose-lipid complexes, thermal
      analysis of the 2 soy breads stored for 10 d (ambient conditions) demonstrated no
      significant difference in water distribution and starch retrogradation (P <
      0.05). Lastly, SD-B was determined to have 32% of total isoflavones occurring in
      the aglycone form compared to 17% in Y-B. These findings warrant further
      investigation of sourdough fermentation as a processing technique for quality and
      nutritional enhancement of soy-based baked goods. 

PMID- 24024977
TI  - High-resolution scanning tunneling microscopy characterization of mixed monolayer
      protected gold nanoparticles.
AB  - Gold nanoparticles protected by a binary mixture of thiolate molecules have a
      ligand shell that can spontaneously separate into nanoscale domains. Complex
      morphologies arise in such ligand shells, including striped, patchy, and Janus
      domains. Characterization of these morphologies remains a challenge. Scanning
      tunneling microscopy (STM) imaging has been one of the key approaches to
      determine these structures, yet the imaging of nanoparticles' surfaces faces
      difficulty stemming from steep surface curvature, complex molecular structures,
      and the possibility of imaging artifacts in the same size range. Images obtained
      to date have lacked molecular resolution, and only domains have been resolved.
      There is a clear need for images that resolve the molecular arrangement that
      leads to domain formation on the ligand shell of these particles. Herein we
      report an advance in the STM imaging of gold nanoparticles, revealing some of the
      molecules that constitute the domains in striped and Janus gold nanoparticles. We
      analyze the images to determine molecular arrangements on parts of the particles,
      highlight molecular "defects" present in the ligand shell, show persistence of
      the features across subsequent images, and observe the transition from quasi
      molecular to domain resolution. The ability to resolve single molecules in the
      ligand shell of nanoparticles could lead to a more comprehensive understanding of
      the role of the ligand structure in determining the properties of mixed-monolayer
      protected gold nanoparticles. 

PMID- 24024978
TI  - Service user involvement in pre-registration children's nursing education: the
      impact and influence on practice: a case study on the student perspective.
AB  - This article reports on a study that aimed to conduct an in-depth investigation
      into the impact of user involvement on student learning and subsequent influence
      on practice as a qualified nurse. This was undertaken through a single case study
      that followed a narrative inquiry approach. UK policy has recommended user
      involvement in healthcare education for a number of years; this has in turn
      increased requirements for involvement from Professional, Statutory and
      Regulatory Bodies. The Nursing and Midwifery Council (NMC, 2010) now requires
      program providers to clearly demonstrate how service users and carers contribute
      to program design, delivery and assessment. Although the literature base is
      expanding there remains limited evidence of the impact of involvement on student
      learning and improved outcomes for patients. Narratives were collected from a
      children's nursing student on completion of her 3-year nurse education program
      and again after practicing as a qualified children's nurse for 1 year. Taking
      part in the research enabled the participant to consider and reflect on her
      experience of user involvement in her education and training. Analysis followed
      an interpretive approach utilizing "The Listening Guide" (Doucet & Mauthner 2008)
      with the researcher's interpretation of how the experience was conveyed with
      clear acknowledgement of reflexivity.The findings identified central themes of
      authenticity, knowledge of self, resilience and coping, professional
      relationships, personalization of care, and influence on practice. This
      demonstrates transformative learning and support to practice, with preparation
      for situations and ideas on how to respond with empathy and compassion. This
      article contributes to the emerging evidence base specifically from a children's
      nursing perspective, an area with a dearth of published material. Further
      research with a range of students is required to explore the lasting impact on
      practice. 

PMID- 24024980
TI  - The role of vagus nerve overactivity in the increased incidence of pneumonia
      following traumatic brain injury.
AB  - Nosocomial infections, pneumonia in particular, are well-known complications of
      traumatic brain injury (TBI), which are associated with a worse neurological
      outcome. This review aims to explore the role of vagus nerve activity in
      immunomodulation as a causative factor. A MEDLINE search revealed numerous
      reports published over the last decade describing the "cholinergic anti
      inflammatory pathway" between the vagus nucleus and leukocyte activity. Using a
      combination of lipopolysaccharide stimulation and vagotomy, it has been shown
      that the parasympathetic fibres terminating in the spleen reduce tumour necrosis
      factor production. Further pharmacological and receptor knockout studies have
      identified the alpha7 subtype of nicotinic receptors as the likely target for
      this. Vagal activity also induces changes in neutrophil chemotaxis through
      altered expression of the CD11b integrin which is abolished by splenectomy. By
      extrapolating this evidence we suggest a possible mechanism for immunosuppression
      following TBI which also has the potential to be targeted to reduce the incidence
      of pneumonia. Whilst there is strong supporting evidence for the role of vagal
      nerve overactivity in post-TBI pneumonia, there have yet to be any clinical
      investigations and further study is required.

PMID- 24024979
TI  - Elevated thyroid autoantibodies and intracranial stenosis in stroke at an early
      age.
AB  - BACKGROUND: Previous studies have shown that hyperthyroidism was related to
      Moyamoya disease and intracranial artery stenosis. However, it is not clear
      whether thyroid hormone or thyroid autoantibodies was associated with them. AIMS
      AND/OR HYPOTHESIS: Thyroid autoimmunity was previously shown to be associated
      with Moyamoya disease. Our study aimed to investigate the association between
      thyroid autoantibodies and intracranial large artery stenosis in young ischemic
      stroke patients with apparent euthyroid states. METHODS: We retrospectively
      reviewed first-onset ischemic stroke patients (age <=55 years old) consecutively
      admitted to a single academic center. Intracranial large artery stenosis was
      defined as >=50% luminal diameter narrowing. We compared demographic profiles,
      risk factors (age, hypertension, diabetes, current smoker, atrial fibrillation,
      hyperlipidemia), thyroid function test, and thyroid autoantibodies including
      antithyroperoxidase antibody and antithyroglobulin antibody between patients with
      and without intracranial large artery stenosis. We also performed multivariate
      logistic regression analysis to evaluate the association between thyroid
      autoantibodies and intracranial large artery stenosis. RESULTS: A total of 351
      patients were analyzed. The mean age of the patients was 47.0 +/- 7.7 (range, 10
      55 years), and 252 (71.8%) patients were male. We identified intracranial large
      artery stenosis in 121 (34.5%) patients. Patients with intracranial large artery
      stenosis showed a higher frequency of elevated antithyroperpxidase antibody
      levels in comparison with nonintracranial large artery stenosis group (16.5% vs.
      3.9%, P < 0.001). After adjusting for covariates, the presence of elevated
      antithyroperpxidase antibody levels (odds ratio: 5.318; 95% confidence interval:
      2.157-13.110, P < 0.001), age (odds ratio: 1.037; 95% confidence interval: 1.002
      1.073, P = 0.039), and atrial fibrillation (odds ratio: 0.091; 95% confidence
      interval: 0.011-0.756, P = 0.027) was independently associated with intracranial
      large artery stenosis. CONCLUSIONS: Thyroid autoantibodies may be associated with
      the presence of intracranial large artery stenosis in young stroke patients,
      potentially providing insight on immune pathogenesis of intracranial large artery
      stenosis.

PMID- 24024981
TI  - Overnight storage of whole blood: cooling and transporting blood at room
      temperature under extreme temperature conditions.
AB  - BACKGROUND AND OBJECTIVES: Many countries allow the overnight storage of whole
      blood (WB) at ambient temperature. Some countries, such as Canada, also require a
      rapid cooling of WB with an active cooling system. Given the significant
      operational constraints associated with current cooling systems, an alternative
      method for cooling and transporting WB at 20-24 degrees C was evaluated.
      MATERIALS AND METHODS: Phase 22 cooling packs (TCP Reliable Inc., USA) were used
      in combination with vacuum-insulated panel (VIP) boxes. Temperature profiles of
      simulated WB units were studied in extreme temperatures (-35 and 40 degrees C).
      The quality of blood components prepared using Phase 22 packs and CompoCool-WB
      (Fresenius HemoCare, Germany) was studied. RESULTS: Phase 22 packs reduced the
      temperature of simulated WB bags from 37 to 24 degrees C in 1.7 +/- 0.2 h. Used
      in combination with VIP boxes, Phase 22 packs maintain the temperature of bags
      between 20 and 24 degrees C for 15 and 24 h, compared to 2 and 11 h with
      CompoCool-WB, when exposed at -35 and 40 degrees C, respectively. The quality of
      platelet concentrates and plasma was comparable, regardless of the cooling system
      used. For red blood cell units, per cent haemolysis on day 42 was slightly higher
      in products prepared after cooling with Phase 22 packs compared to CompoCool-WB
      (0.33 +/- 0.15% vs. 0.21 +/- 0.06%; P < 0.05). CONCLUSIONS: Phase 22 packs
      combined with VIP boxes are an acceptable alternative to butane-1,4-diol cooling
      systems. This system allows blood manufacturers to transport WB to processing
      facilities in a broad range of environmental conditions.

PMID- 24024982
TI  - Severe late-onset multisystem cytomegalovirus infection in a premature neonate
      previously treated for congenital infection.
AB  - BACKGROUND: Cytomegalovirus is the most common pathogen causing congenital
      infection and can result in significant neurodevelopmental adverse outcomes. For
      this reason, it is the standard of care in many regions to treat congenital
      cytomegalovirus infection involving the brain with six weeks of ganciclovir.
      There have been no reports in the published literature of significant
      cytomegalovirus neonatal infection in infants previously treated for congenital
      infection. CASE PRESENTATION: A preterm male infant with congenital symptomatic
      cytomegalovirus infection was initially treated with over 8 weeks of ganciclovir
      between the ages of 3 and 14 weeks. At four months chronologic age, just prior to
      planned discharge, he developed an episode of life-threatening multisystem
      cytomegalovirus disease notable for severe pneumonitis, encephalitis, hepatitis,
      and disseminated intravascular coagulation. This disease resolved after re
      treatment with a prolonged course of intravenous ganciclovir and oral
      valganciclovir. CONCLUSIONS: Clinicians should be aware of the possibility of
      recurrence of congenital cytomegalovirus infection, especially in preterm
      infants. Serial plasma cytomegalovirus viral load monitoring may have a role in
      the management of premature infants treated with ganciclovir; had the diagnosis
      of recrudescent cytomegalovirus infection been considered sooner, specific
      therapy might have been more quickly initiated and perhaps further morbidity
      would have been prevented.

PMID- 24024983
TI  - Efficacy of a new mouth rinse formulation based on 0.07% cetylpyridinium chloride
      in the control of plaque and gingivitis: a 6-month randomized clinical trial.
AB  - AIM: To assess the efficacy of a 0.07% cetylpyridinium chloride (CPC) mouth rinse
      in the control of plaque and gingival inflammation during a 6-month period.
      MATERIAL AND METHODS: Adult subjects with moderate gingivitis were selected
      [>=40% bleeding on marginal probing (BOMP)]. After retrieving microbiological
      samples and evaluating the clinical parameters (plaque, BOMP and stain indexes),
      a professional prophylaxis was performed and subjects were randomly assigned to
      the test (CPC mouth rinse) or to the placebo group. Subjects were re-assessed
      after 3 and 6 months. RESULTS: A total of 67 patients (35 test, 32 placebo) were
      included in the analysis. At 6 months, intra-group significant plaque reductions
      were observed in the test group (0.691, p < 0.001), but not in the placebo
      (0.181, p = 0.653). At 6 months, the mean BOMP values were lower in the test
      group (p = 0.052). Changes between baseline and 6 months were significantly
      higher in the test group both for plaque (p = 0.002) and BOMP (p = 0.037) when
      compared with the placebo. A microbiological impact was observed in the test
      group, especially for Prevotella intermedia. CONCLUSION: The evaluated 0.07% CPC
      based mouth rinse, used three times per day adjunctively to mechanical tooth
      cleaning, prevents plaque accumulation and gingival inflammation, as compared to
      the placebo, for at least 6 months.

PMID- 24024984
TI  - Inactivation of faecal indicator bacteria in a roof-captured rainwater system
      under ambient meteorological conditions.
AB  - AIMS: In this study, faecal indicator bacteria (FIB) namely Escherichia coli and
      Enterococcus spp. were seeded into slurries of possum faeces and placed on the
      roof and in the gutter of a roof-captured rainwater (RCR) system. The persistence
      of FIB in these circumstances was determined under ambient climatic conditions.
      FIB persistence was also determined under in situ conditions in tank water using
      diffusion chambers. METHODS AND RESULTS: The numbers of surviving FIB at
      different time intervals were enumerated using culture-based methods. Both FIB
      were rapidly inactivated on the roof under sunlight conditions (T(90) = 2 h)
      compared with shade conditions (T(90) = 9-53 h). Significant differences were
      observed between sunlight and shade conditions on the roof for both T90 values of
      E. coli (P < 0.001) and Enterococcus spp. (P < 0.001). E. coli showed biphasic
      inactivation patterns under both clean and unclean gutter conditions.
      Enterococcus spp., however, showed rapid inactivation (T(90) = 2 h for the clean
      gutter and T(90) = 6 h for the unclean gutter) compared with E. coli (T(90) = 22
      h for the clean gutter and T(90) = 20 h for the unclean gutter). Significant
      differences were also observed between the T(90) values of E. coli and
      Enterococcus spp. for both clean (P < 0.001) and unclean (P < 0.001) gutters.
      Both E. coli and Enterococcus spp. showed nonlinear biphasic inactivation in tank
      water. Significant difference was observed between the T(90) value of E. coli
      inactivation compared with Enterococcus spp. (P < 0.001) in the tank water.
      CONCLUSIONS: In this study, FIB were observed to survive longer (T(90) = 9-53 h)
      on the roof under shade conditions compared with sunlight conditions (T(90) = 2
      h). If there is a rainfall event within two to three days after the deposition of
      faecal maters on the roof, it is highly likely that FIB would be transported to
      the tank water. When introduced into the tank, a relatively slow inactivation
      process may take place (T(90) = 38-72 h). SIGNIFICANCE AND IMPACT OF THE STUDY:
      The presence of FIB in water indicates faecal pollution and potential presence of
      enteric pathogens. Therefore, the information on the resilience of FIB, as
      obtained in this study, can be used for indirect assessment of health risks
      associated with using roof-captured rainwater for potable and nonpotable
      purposes.

PMID- 24024987
TI  - Trophic cascades following the disease-induced decline of an apex predator, the
      Tasmanian devil.
AB  - As apex predators disappear worldwide, there is escalating evidence of their
      importance in maintaining the integrity and diversity of the ecosystems they
      inhabit. The largest extant marsupial carnivore, the Tasmanian devil (Sarcophilus
      harrisii) is threatened with extinction from a transmissible cancer, devil facial
      tumor disease (DFTD). The disease, first observed in 1996, has led to apparent
      population declines in excess of 95% in some areas and has spread to more than
      80% of their range. We analyzed a long-term Tasmania-wide data set derived from
      wildlife spotlighting surveys to assess the effects of DFTD-induced devil decline
      on populations of other mammals and to examine the relative strength of top-down
      and bottom-up control of mesopredators between 2 regions with different
      environmental conditions. Collection of the data began >10 years before DFTD was
      first observed. A decrease in devil populations was immediate across diseased
      regions following DFTD arrival, and there has been no indication of population
      recovery. Feral cats (Felis catus) increased in areas where the disease was
      present the longest, and feral cat occurrence was significantly and negatively
      associated with devils. The smallest mesopredator, the eastern quoll (Dasyurus
      viverrinus), declined rapidly following DFTD arrival. This result suggests the
      species was indirectly protected by devils through the suppression of larger
      predators. Rainfall deficiency was also a significant predictor of their decline.
      Environmental variables determined the relative importance of top-down control in
      the population regulation of mesopredators. In landscapes of low rainfall and
      relatively higher proportions of agriculture and human settlement, top-down
      forces were dampened and bottom-up forces had the most effect on mesopredators.
      For herbivore prey species, there was evidence of population differences after
      DFTD arrival, but undetected environmental factors had greater effects. The
      unique opportunity to assess population changes over extensive temporal and
      spatial scales following apex predator loss further demonstrated their role in
      structuring ecosystems and of productivity in determining the strength of top
      down control.

PMID- 24024985
TI  - Fluocinolone acetonide partially restores the mineralization of LPS-stimulated
      dental pulp cells through inhibition of NF-kappaB pathway and activation of AP-1
      pathway.
AB  - BACKGROUND AND PURPOSE: Fluocinolone acetonide (FA) is commonly used as a
      steroidal anti-inflammatory drug. We recently found that in dental pulp cells
      (DPCs) FA has osteo-/odonto-inductive as well as anti-inflammatory effects.
      However, the mechanism by which FA induces these effects in DPCs is poorly
      understood. EXPERIMENTAL APPROACH: The effect of FA on the mineralization of DPCs
      during inflammatory conditions and the underlying mechanism were investigated by
      real-time PCR, Western blot, EMSA, histochemical staining, immunostaining and
      pathway blockade assays. KEY RESULTS: FA significantly inhibited the inflammatory
      response in LPS-treated DPCs not only by down-regulating the expression of pro
      inflammation-related genes, but also by up-regulating the expression of the anti
      inflammatory gene PPAR-gamma and mineralization-related genes. Moreover,
      histochemical staining and immunostaining showed that FA could partially restore
      the expressions of alkaline phosphatase, osteocalcin and dentin
      sialophosphoprotein (DSPP) and mineralization in LPS-stimulated DPCs. Real-time
      PCR and Western blot analysis revealed that FA up-regulated DSPP and runt-related
      transcription factor 2 expression by inhibiting the expression of phosphorylated
      NF-kappaB P65 and activating activator protein-1 (AP-1) (p-c-Jun and Fra-1).
      These results were further confirmed through EMSA, by detection of NF-kappaB DNA
      binding activity and pathway blockade assays using a NF-kappaB pathway inhibitor,
      AP-1 pathway inhibitor and glucocorticoid receptor antagonist. CONCLUSIONS AND
      IMPLICATIONS: Inflammation induced by LPS suppresses the mineralization process
      in DPCs. FA partially restored this osteo-/odonto-genesis process in LPS-treated
      DPCs and had an anti-inflammatory effect through inhibition of the NF-kappaB
      pathway and activation of the AP-1 pathway. Hence, FA is a potential new
      treatment for inflammation-associated bone/teeth diseases.

PMID- 24024986
TI  - Transcriptome analysis of two buffalograss cultivars.
AB  - BACKGROUND: Buffalograss [Buchloe dactyloides (Nutt.) Engel. syn. Bouteloua
      dactyloides (Nutt.) Columbus] is a United States native turfgrass species that
      requires less irrigation, fungicides and pesticides compared to more commonly
      used turfgrass species. In areas where water is limited, interest in this grass
      species for lawns is increasing. While several buffalograss cultivars have been
      developed through buffalograss breeding, the timeframe for new cultivar
      development is long and is limited by a lack of useful genetic resources. Two
      high throughput next-generation sequencing techniques were used to increase the
      genomic resources available for buffalograss. RESULTS: Total RNA was extracted
      and purified from leaf samples of two buffalograss cultivars. '378' and
      'Prestige' cDNA libraries were subjected to high throughput sequencing on the
      Illumina GA and Roche 454 Titanium FLX sequencing platforms. The 454 platform (3
      samples) produced 1,300,885 reads and the Illumina platform (12 samples)
      generated approximately 332 million reads. The multiple k-mer technique for de
      novo assembly using Velvet and Oases was applied. A total of 121,288 contigs were
      assembled that were similar to previously reported Ensembl commelinid sequences.
      Original Illumina reads were also mapped to the high quality assembly to estimate
      expression levels of buffalograss transcripts. There were a total of 325
      differentially expressed genes between the two buffalograss cultivars. A glycosyl
      transferase, serine threonine kinase, and nb-arc domain containing transcripts
      were among those differentially expressed between the two cultivars. These genes
      have been previously implicated in defense response pathways and may in part
      explain some of the performance differences between 'Prestige' and '378'.
      CONCLUSIONS: To date, this is the first high throughput sequencing experiment
      conducted on buffalograss. In total, 121,288 high quality transcripts were
      assembled, significantly expanding the limited genetic resources available for
      buffalograss genetic studies. Additionally, 325 differentially expressed
      sequences were identified which may contribute to performance or morphological
      differences between 'Prestige' and '378' buffalograss cultivars.

PMID- 24024988
TI  - Economic burden of healthcare-associated infection in US acute care hospitals:
      societal perspective.
AB  - BACKGROUND: Assessing the costs of healthcare-associated infection (HAI) is
      challenging. Methodological issues abound. Previous estimates have been derived
      in diverse ways from varied perspectives in different settings with dissimilar
      data. RESULTS can be confusing. Full societal costs, which are more inclusive
      than commonly reported direct hospital costs, have never been fully measured or
      reported. OBJECTIVE: To update, combine, and expand previous cost estimates to
      determine the annual societal burden of illness (direct medical, non-medical, and
      indirect costs) arising from HAIs in US acute-care hospitals. METHODS: The
      research approach encompassed literature and internet searches; reference
      identification, selection, and review; then data abstraction, compilation, and
      analyses to estimate full societal costs. Previously published systemic reviews,
      surveillance reports, and individual clinical studies, along with newly computed
      component costs, all contributed to final estimates. RESULTS: HAIs in US acute
      care hospitals lead to direct and indirect costs totaling $96-$147 billion
      annually. These results are subject to the same limitations as previous studies
      from which contributing data were derived. CONCLUSION: The enormous clinical and
      economic burden of infection places HAIs high on the list of devastating and
      costly illnesses, such as cancer, heart attack, stroke, and diabetes, thereby
      mandating further research and greater efforts to contain a pressing healthcare
      problem.

PMID- 24024989
TI  - Acute denervation injury.

PMID- 24024990
TI  - Quid pro quo in orthopedics.

PMID- 24024991
TI  - Prevention of cortical breach during placement of an antegrade intramedullary
      femoral nail.
AB  - The radius of curvature of femoral intramedullary nails does not match the
      average radius of curvature of the human femur. Anterior cortical breach of the
      distal femur during nail placement has been reported in certain fracture
      patterns, in femora with a smaller radius of curvature, and at the starting point
      of the nail. The authors describe a novel technique used to prevent anterior
      cortical disruption of the femur using multiple percutaneously placed Steinmann
      pins. This technique ensures safe passage of medullary reamers and the femoral
      nail. 

PMID- 24024992
TI  - Conversion hemiarthroplasty and valgus osteotomy after failed ORIF of hip
      intertrochanteric fractures.
AB  - Hip arthroplasty after open reduction and internal fixation of the proximal femur
      presents a challenge to reconstructive surgeons. Bony defects, fracture malunion,
      and non-union increase the risk of complications, including intraoperative
      fracture, unrecognized perforation, and trochanteric non-union. The authors
      describe a novel surgical technique using conversion hemiarthroplasty and valgus
      osteotomy for failed open reduction and internal fixation of intertrochanteric
      hip fractures. The described surgical technique resulted in trochanteric
      advancement and preservation of the bone stock in the intertrochanteric region.
      This technique was successful in eliminating pain and restoring ambulation and
      abductor function and resulted in stable ingrowth and healing in these patients. 

PMID- 24024993
TI  - Cervical myelopathy.

PMID- 24024994
TI  - Outcomes of short stems in total hip arthroplasty.
AB  - Short-stem total hip arthroplasty has been proposed as a bone-conserving
      procedure for the younger and more active population undergoing total hip
      arthroplasty. Although various short stems are currently available, no studies
      compare the outcomes between these stems. The aim of the current study was to
      conduct a systematic review of the clinical and radiographic outcomes of the
      various short stems that have been approved for use in the United States by the
      Food and Drug Administration. Outcomes that were assessed included implant
      survivorship, Harris Hip scores, thigh pain, periprosthetic fracture, subsidence,
      proximal stress shielding, and the prevalence of stem malalignment and
      inappropriate implant sizing. 

PMID- 24024995
TI  - Indications for 2-incision anterior cruciate ligament surgery.
AB  - Two-incision anterior cruciate ligament reconstruction uses an outside-in femoral
      drilling technique. Advantages include anatomic femoral tunnel placement and
      increased versatility with regard to graft position and fixation in the femoral
      tunnel or distal femur. The authors believe that transtibial femoral tunnel
      drilling is inferior because of nonanatomic femoral tunnel placement and the
      requirement of the posterior footprint placement of the tibial tunnel.
      Indications for outside-in femoral drilling include revision anterior cruciate
      ligament reconstruction, drilling an all-epiphyseal tunnel in skeletally immature
      patients, long bone-patellar tendon-bone autografts when using more than 45 mm of
      tendon, and cases in which the leg cannot be hyperflexed for accessory
      anteromedial portal drilling. 

PMID- 24024996
TI  - The effect of recombinant human bone morphogenetic protein-2 in single-level
      posterior lumbar interbody arthrodesis.

PMID- 24024997
TI  - Isolated subtalar dislocation.
AB  - EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be
      able to: 1. Understand the etiology, epidemiology, and importance of treatment of
      isolated subtalar dislocation. 2. Understand the most common management practices
      when treating isolated subtalar dislocation and identify variations in management
      that may affect prognosis. 3. Consolidate reported patient outcomes as they
      pertain to variations in management strategies to explore which practices may
      provide the best prognosis after treatment of isolated subtalar dislocation. 4.
      Highlight the importance of further study to determine the best course of
      management for isolated subtalar dislocation regarding variables in treatment.
      This study reviews the literature on isolated subtalar dislocation published
      within the past 5 years. Variation in management existed mostly in the categories
      of treatment choice, immobilizer type, and period of immobilization, with closed
      reduction, closed reduction and percutaneous pinning, below-knee casting, less
      than 4 weeks of immobilization, and 6 weeks of immobilization reporting good
      results. The good results described after the addition of percutaneous K-wire
      fixation to the initial treatment method of isolated subtalar dislocation,
      immobilization via below-knee casting, and shorter periods of immobilization
      suggest that these practices may be useful for the treatment of this rare injury.

PMID- 24024999
TI  - Partial ACL tears: anatomic reconstruction versus nonanatomic augmentation
      surgery.
AB  - Treatment of partial anterior cruciate ligament (ACL) tears requires ACL remnant
      preservation. The goal of this study was to compare the outcome of anatomic
      reconstruction of the torn bundle with nonanatomic augmentation using the over
      the-top femoral route. Fifty-two athletes (mean age, 23.3 years) with partial ACL
      lesions underwent anatomic reconstruction (n=26) or nonanatomic augmentation
      (n=26). Intraoperative damage of the healthy bundle that required a standard ACL
      reconstruction occurred in 2 patients in the anatomic reconstruction group.
      International Knee Documentation Committee (IKDC) score, Tegner score, and
      arthrometer evaluation were used pre-operatively and at follow-up for up to 5
      years postoperatively. One failure occurred in the anatomic reconstruction group.
      Mean IKDC subjective score at follow-up was 88.2 +/- 5.7 in the anatomic
      reconstruction group and 90.2 +/- 4.7 in the nonanatomic augmentation group.
      According to the IKDC objective score at final follow-up, 96% of knees in the
      nonanatomic augmentation group were normal vs 87.5% in the anatomic
      reconstruction group. No significative differences were observed between the 2
      groups at final follow-up. Anteromedial bundle reconstruction showed
      significantly lower IKDC subjective and objective scores and higher residual
      instability values as evaluated with the arthrometer compared with posterolateral
      bundle reconstruction (P=.017). The surgical treatment of ACL partial tears is
      demanding. Adapted portals, perfect control of the tunnel drilling process, and
      intercondylar space management are required in anatomic reconstruction. The
      nonanatomic augmentation technique is simpler, providing excellent durable
      results over time with a lower complication rate. Anteromedial bundle
      reconstruction is associated with a poorer outcome, especially when performed
      with anatomic reconstruction.

PMID- 24025000
TI  - Posterolateral corner of the knee: microsurgical analysis of anatomy and
      morphometry.
AB  - Reconstruction of the posterolateral corner (PLC) of the knee is essential to
      restore knee joint function. Controversy exists regarding a standardized
      nomenclature, the connective attachments and the relationships between them, and
      the frequency of occurrence among all structures of the PLC. Thirty human
      cadaveric knee specimens were investigated. The lateral collateral ligament,
      popliteus tendon, popliteofibular ligament, fabellofibular ligament, arcuate
      ligament, oblique popliteal ligament, posterior meniscofemoral ligament, and
      popliteal hiatus (including the popliteomeniscal ligaments) were studied. The
      length, diameter, variations, course, and morphology of these structures, as well
      as the position and dimension of the insertion, were measured and referenced the
      footprints to adjacent bony landmarks. Compared with existing studies, the
      lateral collateral ligament footprint was more proximal to the lateral femoral
      epicondyle (average, 3.61 +/- 0.75 mm) and the popliteus tendon insertion was
      more distal and anterior to the lateral collateral ligament footprint (average,
      5.69 +/- 1.36 mm and 4.97 +/- 1.73 mm, respectively). Only minor data have been
      published on the fabellofibular ligament (average length, 33.79 +/- 4.98 mm;
      average diameter, 4.04 +/- 1.22 mm), arcuate ligament (average length, 31.54 +/-
      2.82 mm; average diameter, 7.27 +/- 1.56 mm), oblique popliteal ligament (average
      length, 45.56 +/- 4.67 mm; average diameter, 14.90 +/- 4.67 mm), posterior
      meniscofemoral ligament (average length, 23.75 +/- 3.17 mm; average diameter,
      3.62 +/- 1.03 mm), and popliteomeniscal ligaments (average mediolateral popliteal
      hiatus diameter, 9.83 +/- 2.16 mm; average superoinferior popliteal hiatus
      diameter, 8.23 +/- 1.86 mm).

PMID- 24025001
TI  - Intra-articular morphine versus bupivacaine for postoperative pain management.
AB  - The purpose of this study was to determine whether morphine would be as effective
      as bupivacaine for postoperative pain control after knee arthroscopy with no
      worsening of the side effect profile. Eighty-two patients who underwent partial
      meniscectomy, chondral debridement, or both were prospectively randomized to
      receive 10 mg of morphine (10-cc volume) or 10 cc of .5% bupivacaine immediately
      postoperatively. Visual analog scale scores and side effect profiles were
      recorded in the postanesthesia care unit, in the transitional care unit, and then
      every 4 hours postoperatively until 24 hours. In-hospital data were available for
      all 82 patients, but postdischarge data were available for only 64 patients.
      Visual analog scale scores in the postanesthesia care unit decreased from 3.4 on
      admission to 2.4 on discharge for the morphine group and from 2.6 to 2.4 for the
      bupivacaine group (P>.217, all time points). Medication use was the same for both
      groups in the hospital (62% and 78%, respectively) with no statistical
      difference. Visual analog scale scores decreased from 3.0 to 1.5 for the morphine
      group and from 2.8 to 1.8 for the bupivacaine group between 4 and 24 hours
      postoperatively (P>.376, all time points). Medication use decreased between 4 and
      24 hours postoperatively for both groups, from 71.7% to 52.9%, respectively, with
      no statistical difference at all time points. Four patients in the morphine group
      and 1 patient in the bupivacaine group experienced side effects. This study
      indicates that 10 mg of intra-articular morphine is as effective as 10 cc of .5%
      bupivacaine for postoperative pain control for partial meniscectomy and chondral
      debridement of the knee. It minimally increases side effects initially and
      circumvents the issue of chondral toxicity of bupivacaine. 

PMID- 24025002
TI  - Cadaver training module for teaching thoracic pedicle screw placement to
      residents.
AB  - Surgical training using simulators has been shown to be highly effective but is
      not available for some applications and is too expensive for many programs. The
      authors piloted a cadaver-based module with the goal of objectively measuring and
      significantly improving orthopedic residents' surgical skills in placing thoracic
      pedicle screws, an advanced procedure. An experienced spine surgeon placed
      thoracic pedicle screws in 7 cadavers (T1-T12) to establish the skilled accuracy
      rate. For this pilot study, 3 orthopedic residents unfamiliar with the procedure
      were given didactic training for safe thoracic pedicle screw insertion. Each
      resident instrumented alternating sides of 5 consecutive cadavers (T1-T12). Screw
      positions were graded by computed tomography in a blinded fashion, with accuracy
      defined as no shank breach of the pedicle or vertebral body. Results were
      reviewed with the residents, instruction was repeated, and alternating sides of 5
      cadavers were instrumented by the residents. The experienced surgeon accurately
      placed 67 (82%) of 82 pedicle screws. Residents accurately placed 80 (44%) of 180
      pedicle screws in the initial set of specimens and 105 (58%) of 180 pedicle
      screws in the second set of specimens (P=.01). Accuracy varied significantly
      among residents before but not after computed tomography review. The study's
      results show that a cadaver-based training module that resembles the clinical
      setting can be used to teach complex surgical skills to orthopedic residents. 

PMID- 24025003
TI  - Mechanical assessment of local bone quality to predict failure of locked plating
      in a proximal humerus fracture model.
AB  - The importance of osteoporosis in proximal humerus fractures is well recognized.
      However, the local distribution of bone quality in the humeral head may also have
      a significant effect because it remains unclear in what quality of bone screws of
      standard implants purchase. The goal of this study was to investigate whether the
      failure of proximal humerus locked plating can be predicted by the DensiProbe
      (ARI, Davos, Switzerland). A 2-part fracture with metaphyseal impaction was
      simulated in 12 fresh-frozen human cadaveric humeri. Using the DensiProbe, local
      bone quality was determined in the humeral head in the course of 6 proximal
      screws of a standard locking plate (Philos; Synthes GmbH, Solothurn,
      Switzerland). Cyclic mechanical testing with increasing axial loading until
      failure was performed. Bone mineral density (BMD) significantly correlated with
      cycles until failure. Head migration significantly increased between 1000 and
      2000 loading cycles and significantly correlated with BMD after 3000 cycles.
      DensiProbe peak torque in all screw positions and their respective mean torque
      correlated significantly with the BMD values. In 3 positions, the peak torque
      significantly correlated with cycles to failure; here BMD significantly
      influenced mechanical stability. The validity of the DensiProbe was proven by the
      correlation between its peak torque measurements and BMD. The correlation between
      the peak torque and cycles to failure revealed the potential of the DensiProbe to
      predict the failure of locked plating in vitro. This method provides information
      about local bone quality, potentially making it suitable for intraoperative use
      by allowing the surgeon to take measures to improve stability. 

PMID- 24025004
TI  - Steroid injections in the upper extremity: experienced clinical opinion versus
      evidence-based practices.
AB  - A survey regarding upper-extremity steroid injection practices was distributed to
      all active members of the American Society for Surgery of the Hand (ASSH) and
      American Shoulder and Elbow Surgeons (ASES) using SurveyMonkey. Response rates
      for the ASSH and ASES were 26% and 24%, respectively. The potency-adjusted dose
      of steroid injected for common hand and wrist injections ranged from 0.375 to
      133.33 mg and for shoulder injections ranged from 0.375 to 250 mg. These ranges
      span 356-fold and 667-fold differences, respectively. Potency-adjusted doses
      differed significantly between steroid types for all injections evaluated in this
      study. American Society for Surgery of the Hand members gave significantly
      smaller doses of steroid for the glenohumeral and acromioclavicular joints than
      ASES members. Only 9% of respondents based injection practice on a scientific
      reference. Sixteen percent of ASSH and 31% of ASES respondents reported no
      specific rationale for their steroid injection practice; 78% of ASSH and 52% of
      ASES respondents attributed their rationale to some kind of instruction from
      their mentors or colleagues. Upper-extremity surgeons demonstrate substantial
      variability in their practice of steroid injections, with up to a 667-fold range
      in steroid dose. Experienced clinical opinion is the principal rationale for
      these injection practices; little rationale is based on formal scientific
      evidence. 

PMID- 24025005
TI  - Patient perception of physician reimbursement for common hand surgical
      procedures.
AB  - Health care-related costs have been the focus of intense scrutiny in politics and
      in the media. However, public perception of physician reimbursement is poorly
      understood. The purpose of this study was to determine patient perception of
      physician reimbursement for 2 common hand surgery procedures: carpal tunnel
      release and open reduction and internal fixation of a distal radius fracture.
      Anonymous surveys were completed by 132 patients in an outpatient hand and upper
      extremity practice. The surveys asked patients to estimate reasonable surgeon
      fees and actual Medicare reimbursement for 2 common hand surgery procedures
      (carpal tunnel release and internal fixation of a distal radius fracture) and 2
      common surgical procedures (coronary artery bypass and appendectomy). On average,
      patients estimated that a reasonable surgeon fee for carpal tunnel release and 90
      days of postoperative care was $2629 and that actual Medicare reimbursement was
      $1891. Patients estimated that a reasonable surgeon fee for internal fixation of
      an extra-articular distal radius fracture and 90 days of postoperative care was
      $3874 and that actual Medicare reimbursement was $2671. Higher level of
      education, annual household income, and insurance status had no statistically
      significant effect on patient estimates of reimbursement. Patients in an
      outpatient hand and upper extremity practice believe that surgeons are reimbursed
      at a rate 3.6 to 4.7 times greater than actual reimbursement. These
      misperceptions highlight the lack of understanding and transparency in health
      care costs and may interfere with the ability of patients to make well-informed
      decisions about health care. 

PMID- 24025006
TI  - Comparison of insertional trauma between suprapatellar and infrapatellar portals
      for tibial nailing.
AB  - The purpose of this study was to determine differences in insertional articular
      trauma in infrapatellar tibial portal and suprapatellar portal intramedullary
      tibial nail insertion techniques. A cadaveric study was performed on 10 matched
      pairs of fresh-frozen adult cadaver lower extremities with intact extensor
      mechanisms. Two study groups with 10 limbs each were created: left lower limbs
      were treated with a standard medial parapatellar nailing portal and right lower
      limbs were treated with a suprapatellar tibial nailing portal. Start points were
      created under fluoroscopic guidance in anteroposterior and mediolateral planes. A
      start wire was placed and opening reaming was performed on the specimens using
      instrumentation specific to the nailing portal. Specimens were then dissected by
      medial parapatellar arthrotomy, revealing the intra-articular condition of the
      knee structures. The border of the tibial entry reamer hole was measured to the
      anterior horns of the menisci, anterior cruciate ligament root, and intermeniscal
      ligament using a digital caliper accurate to 0.02 mm. The structure was
      considered damaged if the structure was obviously damaged on visual inspection or
      if a measurement was less than 1 mm. Impact to intra-articular structures was
      numerically lower in the suprapatellar group (2/10) compared with the
      infrapatellar group (4/10), but the difference was not statistically significant
      between the 2 groups (P=.629). The suprapatellar portal approach to the tibial
      start point demonstrated a lower overall incidence of damage to intra-articular
      structures, but no significant statistical difference existed between the 2
      treatment groups. 

PMID- 24025007
TI  - Antegrade femoral nailing in acetabular fractures requiring a Kocher-Langenbeck
      approach.
AB  - Ipsilateral displaced acetabular and femoral shaft fractures represent a dilemma
      for orthopedic surgeons because antegrade femoral nailing may complicate a Kocher
      Langenbeck acetabular exposure. The goals of this study were to review the
      results of ipsilateral femoral and acetabular fractures treated with antegrade
      femoral nailing and a Kocher-Langenbeck approach and to evaluate the assertion
      that this treatment strategy is associated with increased morbidity. This was a
      retrospective cohort study at a regional Level I trauma center. Sixteen patients
      with a femoral fracture treated with antegrade nailing and an ipsilateral
      acetabular fracture treated with a Kocher-Langenbeck approach were identified.
      One patient died as a result of his injuries, and 2 were not available for long
      term follow-up. One had a deep infection requiring irrigation, debridement, and
      intraveonous antibiotics. One patient developed a hematoma requiring irrigation
      and debridement. At final follow-up, 2 patients had no heterotopic ossification
      about the hip, 4 had Brooker class I heterotopic ossification, 3 had Brooker
      class II heterotopic ossification, 2 had Brooker class III heterotopic
      ossification, and 2 patients had Brooker class IV heterotopic ossification
      requiring excision. Ipsilateral femoral and acetabular fractures represent a rare
      and severe injury constellation. Antegrade nailing of the femur with ipsilateral
      Kocher-Langenbeck exposure for fixation of the acetabulum was not associated with
      excessive rates of wound-healing complications, but the incidence of heterotopic
      ossification was increased. 

PMID- 24025008
TI  - Intraoperative radiation use by trainees during ankle fracture fixation.
AB  - Orthopedic trainees are assessed during training regarding their use of
      radiological screening during operative procedures. The authors investigated
      whether orthopedic trainees' use of fluoroscopic screening during ankle fixation
      operations varied with the 2 variables of consultant supervision and trainee
      experience. Data from operative fixation of isolated Weber B ankle fractures were
      reviewed. The intraoperative radiation dose was retrieved from radiographers'
      data. Operations performed by consultants were used as a control group (n=25
      patients). Trainee supervision was assessed as "trainer in operating room (OR)"
      and "trainer out of OR." Regarding experience, the patients were divided into
      those operated on primarily by trainees in their first (n=36 patients) and in
      their last (n=34 patients) 3 years of formal specialist training. All trainee
      groups used more radiation than consultants. Supervision did not affect the
      radiation use of senior trainees (P<.05). Senior trainees used less radiation
      than their junior peers (P<.02). Junior trainees supervised by a trainer in the
      OR used less radiation than junior trainees supervised by a trainer outside of
      the OR (P<.05). During open reduction and internal fixation of ankle fractures,
      junior orthopedic trainees use less intraoperative radiation when they are
      supervised by a trainer in the OR. The more experience a surgeon has, the less
      fluoroscopic screening is used during operative ankle fixation. 

PMID- 24025009
TI  - Internal fixation of distal metacarpal fractures: new uses for an old plate.
AB  - Certain metacarpal fracture patterns require operative fixation to restore
      anatomy and optimize results. Compared with dorsal plating, the width of the
      minicondylar blade plate buttresses the deforming volar pull of the intrinsics
      and provides a stronger construct. The implant provides firm fixation in the
      juxta-articular fragment with minimal space requirements. Therefore, the purpose
      of this study was to examine the outcomes following the use of a minicondylar
      blade plate for the treatment of distal metacarpal fractures. Twenty-two distal
      metacarpal fractures in 20 patients treated with a minicondylar blade plate were
      retrospectively reviewed. Outcome measures collected included postoperative grip
      strength, range of motion, return to work, and radiographic evidence of osseous
      union. Average range of motion of the metacarpophalangeal joint was 62 degrees 
      postoperatively. Eighty-two percent (18/22) of fractures were able to flex their
      digits to their distal palmar crease. Seventy-one percent (12/17) of patients had
      at least 75% return to grip strength compared with the contralateral side.
      Seventeen patients returned to full activity at a mean of 2.5 months (range, 1-3
      months) postoperatively; 1 patient was on disability, and data were not available
      for the final 2 patients. No major complications occurred. The minicondylar blade
      plate is a safe and effective technique for stabilizing unstable periarticular
      metacarpal fractures. Stable fixation allows for early range of motion, rapid
      return to strength, and a relatively quick return to full work duty. 

PMID- 24025010
TI  - Mixing implants of differing metallic composition in the treatment of upper
      extremity fractures.
AB  - Mixing implants with differing metallic compositions has been avoided for fear of
      galvanic corrosion and subsequent failure of the implants and of bone healing.
      The purpose of this study was to evaluate upper-extremity fractures treated with
      open reduction and internal fixation with metallic implants that differed in
      metallic composition placed on the same bone. The authors studied the effects of
      using both stainless steel and titanium implants on fracture healing, implant
      failure, and other complications associated with this method of fixation. Their
      hypothesis was that combining these metals on the same bone would not cause
      clinically significant nonunions or undo clinical effects from galvanic
      corrosion. A retrospective review was performed of 17 patients with upper
      extremity fractures fixed with metal implants of differing metallic compositions.
      The primary endpoint was fracture union. Eight clavicles, 2 proximal humeri, 3
      distal humeri, 3 olecranons, and 1 glenoid fracture with an average follow-up 10
      months were reviewed. All fractures healed. One patient experienced screw
      backout, which did not affect healing. This study implies that mixing implants
      with differing metallic compositions on the same bone for the treatment of
      fractures does not adversely affect bone healing. No evidence existed of
      corrosion or an increase in complications with this method of treatment. Contrary
      to prior belief, small modular hand stainless steel plates can be used to assist
      in reduction of smaller fracture fragments in combination with anatomic titanium
      plates to obtain anatomic reduction of the fracture without adversely affecting
      healing. 

PMID- 24025011
TI  - Effect of component design in retrieved bipolar hip hemiarthroplasty systems.
AB  - Primary articulation of bipolar hemiarthroplasty systems is at the femoral head
      liner interface. The purpose of this study was to compare observed damage modes
      on 36 retrieved bipolar systems with implant, demographic, intraoperative, and
      radiographic data to elucidate the effects of component design, specifically
      locking mechanism, on clinical performance. Retrieved bipolar hip
      hemiarthroplasty systems of 3 different design types were obtained, disassembled,
      and evaluated macro- and microscopically for varying modes of wear, including
      abrasion, burnishing, embedding, scratching, and pitting. Clinical record review
      and radiographic analysis were performed by a senior orthopedic surgery resident.
      Average bipolar hip hemiarthroplasty system term of service was 46 months (range,
      0.27-187 months). All devices contained wear debris captured within the
      articulating space between the femoral head and liner. In 31% of patients without
      infection, lucency was observed on immediate prerevision radiographs. The system
      with a leaf locking mechanism showed significantly increased radiographically
      observed osteolysis (P=.03) compared with a system with a stopper ring locking
      mechanism. In addition, implant design and observed damage modes, including
      pitting and third-body particle embedding, were significantly associated with
      radiographically observed osteolysis. 

PMID- 24025012
TI  - Adductor tenotomy as a treatment for groin pain in professional soccer players.
AB  - Chronic, exercise-related groin pain is a debilitating condition. Nonoperative
      treatment has limited efficacy, but surgical intervention on the adductor
      abdomino complex may be used to alleviate symptoms and allow return to play
      (RTP). The purpose of this study was to report the outcome of adductor tenotomy
      and hernioplasty for professional soccer players with groin pain. Between 2000
      and 2006, a total of 155 professional and recreational soccer players with
      recalcitrant groin pain (with or without lower abdominal pain) and resistance to
      conservative treatment were included in this retrospective analysis. Ninety-six
      patients were treated with adductor tenotomy and 59 patients were treated with
      combined adductor tenotomy and hernioplasty. No difference in pre- or
      postoperative parameters was detected between groups, apart from abdominal wall
      muscle defects revealed during ultrasound for patients in the combined group. The
      RTP time and subjective and objective outcome measures were compared. A combined
      score was developed to evaluate outcomes that consisted of overall satisfaction
      (50%), RTP time (15%), and Tegner scores (35%). Mean RTP was 11 weeks (range, 4
      36 weeks). Postoperative Tegner score remained 8.2 (same as the preinjury Tegner
      score). Subjective outcome was rated 4.3 of 5. The combined score indicated 80%
      of good or excellent results for both groups. Surgical intervention allows RTP at
      the same level in professional soccer players following failure of nonoperative
      treatments. Athletes with adductor syndrome and accompanying sportsman's hernia
      may benefit from adductor tenotomy alone. 

PMID- 24025013
TI  - Outcome and range of motion using a high-flexion cruciate-retaining TKA.
AB  - Increased knee flexion after total knee arthroplasty (TKA) may contribute to
      patients' increased satisfaction and more active lifestyles. This study evaluated
      a TKA component designed for high flexion (more than 125 degrees ). The design
      features an anatomic sagittal femoral radius with short, flared femoral condyles
      to allow for femoral rollback. Fifty TKA procedures in 47 patients were evaluated
      prospectively regarding clinical outcomes using Knee Society knee and function
      scores, Short Form 12 physical component scores, and flexion measured clinically
      and by digital lateral supine active flexion radiographs. Preoperative and 1-year
      postoperative radiographs were analyzed by an independent observer. Mean maximum
      flexion measured clinically was 115 degrees  preoperatively and 120 degrees  one
      year postoperatively, with 76% of TKAs achieving more than 120 degrees  and 44%
      achieving more than 125 degrees . Sex, body mass index, and preoperative flexion
      were not predictors of postoperative flexion. Mean flexion by radiograph was 108
      degrees  preoperatively and 111 degrees  one year postoperatively, with 31% of
      knees achieving more than 120 degrees  and 14% more than 125 degrees . Mean Knee
      Society knee and function scores and the Short Form 12 physical component scores
      were 52, 55, and 32 preoperatively, respectively, and 89, 77, and 40 one year
      postoperatively, respectively. Of the 50 knees, 84% had improvement in their Knee
      Society function scores, and 76% had improvement in their Short Form 12 physical
      component scores. The study revealed evidence of increased early postoperative
      flexion with the use of a cruciate-retaining high-flexion TKA design. 

PMID- 24025014
TI  - Treatment of spinal fractures in ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic inflammatory spondyloarthropathy with
      the potential for progressive spinal stiffness that ultimately makes patients
      susceptible to spinal fractures with traumatic spinal cord injury from even low
      energy trauma. Treatment of patients with AS and spinal fractures (AS+FX) is
      controversial because, although these patients need especially rigorous
      stabilization, surgery has been associated with an increased risk of
      complications and persistent neurological deficits. The purpose of this
      retrospective case series was to profile patients with AS+FX from a 19-year
      period within the authors' county hospital system, including differences of
      neurological status in patients treated operatively vs nonoperatively. The study
      group comprised 11 patients with AS+FX (9 men and 2 women; mean age, 63 years
      [range, 38-91 years]). The authors reviewed available clinical notes and imaging
      reports. Six patients had posterior operative fixation, and 5 were stabilized
      nonoperatively. By the time of either discharge or final follow-up, 3 of the
      patients treated operatively deteriorated neurologically (2 of them
      preoperatively) and 3 remained stable. Of the patients treated nonoperatively, 3
      remained neurologically intact, 1 deteriorated, and 1 recovered completely. The
      most common complications in all patients were pneumonia and urinary tract
      infection. Operative and nonoperative management produced acceptable outcomes in
      most patients. The authors recommend individualized treatment, accounting for
      patient preferences and comorbidities. 

PMID- 24025015
TI  - Extra-abdominal periosteal desmoid tumor of the third toe.
AB  - Extra-abdominal periosteal desmoid tumors are uncommon nonmetastatic tumors of
      the extremities with a propensity for local recurrence. Lesions in the distal
      extremities are rare; a majority of extra-abdominal lesions occur in more
      proximal portions of the upper and lower extremities. This article reports a
      patient with an extra-abdominal periosteal desmoid tumor in the toe. A 37-year
      old woman had a mass in her left third distal phalanx that was originally noted 3
      years prior to presenting to the authors' institution. She reported the mass
      expanded during pregnancy. The toe was red and elongated and had expanded to
      approximately the same size as her great toe. The plantar aspect of the toe was
      thick and callused, and the toenail was slightly elevated. Marginal excision with
      retention of the nail was performed without complication. The mass was determined
      to be an extra-abdominal periosteal desmoid tumor and was successfully removed
      without recurrence. To date, the patient remains asymptomatic, with no pain and
      complete sensation in her third toe. Although extra-abdominal periosteal desmoid
      tumors have been identified in the extremities, to the authors' knowledge none
      have been reported as far distal as the toe. Identifying this lesion in the
      distal extremity will allow a hasty diagnosis and treatment in future cases of
      similar presentation. Knowledge of the existence of this type of tumor in the
      distal extremity may also assist in narrowing differential diagnoses. 

PMID- 24025016
TI  - Matching osteochondritis dissecans lesions in identical twin brothers.
AB  - Osteochondritis dissecans is a disorder of unknown etiology that can result in
      fragmentation of osteochondral surfaces, most commonly of the knee, shoulder,
      elbow, and ankle. This may lead to sequelae of pain and an inability to
      participate in desired activities. Multiple theories exist as to the true cause
      of the disorder, but none have been fully proven. One such proposed etiology is
      genetic causation. Familial cases of osteochondritis dissecans are rare, yet
      these cases offer support to growing evidence that may support a genetic link.
      This article describes osteochondritis dissecans lesions of the femoral trochlea
      in monozygotic (identical) twins. Both twins presented with similar symptoms 1
      year apart. Neither twin had any clear inciting trauma. Magnetic resonance
      imaging revealed osteochondral lesions in similar positions of the lateral
      trochlear of the same knee in both brothers. Osteochondral autograft transfer and
      tibial tubercle anteromedialization were performed on both patients. An identical
      postoperative protocol was followed, and recovery with full return to sport was
      comparable for the brothers. To the authors' knowledge, only 1 other case report
      exists of osteochondritis dissecans lesions in monozygotic twins. Although debate
      continues regarding the true etiology of this disorder, cases of identical twins
      presenting with a similar disease process are highly suggestive of a genetic
      component and may lead to early identification and treatment of these lesions.
      Continued research in the area of osteochondritis dissecans and its genetic basis
      is needed to completely understand this disorder. 

PMID- 24025017
TI  - Isolated ulnar dorsal cutaneous nerve herpes zoster reactivation.
AB  - Herpes zoster is a viral disease presenting with vesicular eruptions that are
      usually preceded by pain and erythema. Herpes zoster can be seen in any dermatome
      of the body but most commonly appears in the thoracic region. Herpes zoster virus
      is typically transmitted from person to person through direct contact. The virus
      remains dormant in the dorsal ganglion of the affected individual throughout his
      or her lifetime. Herpes zoster reactivation commonly occurs in elderly people due
      to normal age-related decline in cell-mediated immunity. Postherpetic neuralgia
      is the most common complication and is defined as persistent pain or dysesthesia
      1 month after resolution of the herpetic rash. This article describes a healthy
      51-year-old woman who experienced a burning sensation and shooting pain along the
      ulnar dorsal cutaneous nerve. Ten days after the onset of pain, she developed
      cutaneous vesicular eruption and decreased light-touch sensation. Wrist and
      fourth and fifth finger range of motion were painful and slightly limited. Muscle
      strength was normal. Nerve conduction studies indicated an ulnar dorsal cutaneous
      nerve lesion. She was treated with anti-inflammatory and antibiotic drugs and the
      use of a short-arm resting splint. At 5-month follow-up, she reported no residual
      pain, numbness, or weakness. Herpes zoster in the upper extremity may be mistaken
      for entrapment neuropathies and diseases characterized by skin eruptions; ulnar
      nerve zoster reactivation is rarely seen. The authors report an uncommon ulnar
      dorsal cutaneous nerve herpes zoster reactivation. Clinicians should be aware of
      this virus during patients' initial evaluation. 

PMID- 24025018
TI  - Resection of soft tissue tumors extending through the obturator ring.
AB  - Pelvic soft tissue sarcomas are rare tumors often presenting larger than other
      soft tissue sarcomas and can extend into the thigh through various anatomic
      routes. Surgical resection is the main modality of curative treatment. En bloc
      tumor excision with wide, negative margins may reduce the risk of local
      recurrence. Soft tissue sarcomas extending through the obturator foramen create
      unique challenges to operative management. This case report describes 2 cases of
      lipomatous lesions that extend through the obturator foramen, presenting as
      dumbbell-shaped lesions with large intra- and extrapelvis portions. One possible
      surgical approach performed in both patients is detailed with long-term follow
      up. Postoperatively, 1 incidence of infection was reported. Functional outcomes
      were acceptable, with full restoration of ambulation without assistive devices in
      both cases and no hernia observed. Oncologic outcomes included locoregional
      recurrence in 1 patient at 24 months outside the radiation field. The ideal
      primary treatment for all localized soft tissue sarcomas, including those
      extending through the obturator foramen, is resection. However, the unique
      subgroup of obturator ring soft tissue sarcomas has undefined outcomes and
      complications. The authors' goal was to achieve en bloc resection with wide
      negative margins while preserving ipsilateral limb function. The surgical
      approach described in this case study offers a description of feasibility and
      discussion of theoretical and observed complications. 

PMID- 24025019
TI  - Editors, reviewers and the work of the editorial board.

PMID- 24025020
TI  - The effect of 'allergenic' and 'nonallergenic' antibiotics on dog keratinocyte
      viability in vitro.
AB  - BACKGROUND: Immune-mediated adverse drug reactions (drug hypersensitivity) are
      relatively common in veterinary medicine, but their pathogenesis is not well
      understood. For an unknown reason, delayed drug hypersensitivity often targets
      the skin. Antibiotics, especially beta-lactams and sulfonamides, are commonly
      associated with these adverse events. The 'danger theory' hypothesizes that
      'danger' signals, such as drug-induced cell death, might be part of the
      pathogenesis of drug hypersensitivity reactions. HYPOTHESIS/OBJECTIVES: The goal
      of this study was to determine whether antibiotics that are commonly associated
      with cutaneous drug hypersensitivity (allergenic) decrease canine keratinocyte
      viability in vitro more than antibiotics that rarely cause such reactions
      (nonallergenic). METHODS: Immortalized canine keratinocytes (CPEK cells) were
      exposed to a therapeutic range of drug concentrations of four 'allergenic'
      antibiotics (two beta-lactams, i.e. amoxicillin and cefalexin, and two
      sulfonamides, i.e. sulfamethoxazole and sulfadimethoxine) or two 'nonallergenic'
      antibiotics (enrofloxacin and amikacin) over 48 h (2, 4, 8, 24 and 48 h). The
      reactive nitroso metabolite of sulfamethoxazole was also tested. RESULTS:
      Cefalexin (2 mmol/L) significantly decreased cell viability after 48 h (28 +/-
      7%; P = 0.035). The nitroso metabolite of sulfamethoxazole (100 MUmol/L)
      decreased cell viability after 2 h (21 +/- 7%; P = 0.049), but cell numbers were
      increased after 8 h (22 +/- 6%; P = 0.018). In addition, enrofloxacin (500
      MUmol/L) also significantly decreased cell viability by 37% (+/-6%; P = 0.0035)
      at 24 h and by 70% (+/-8%; P < 0.001) at 48 h. CONCLUSION: It appears that the
      effect of drugs on the in vitro viability of dog keratinocytes is not a good
      predictor of the 'allergenic' potential of an antibiotic. Further work is
      required to investigate other drug-induced 'danger' signals in dog keratinocytes
      exposed to 'allergenic' antibiotics in vitro.

PMID- 24025021
TI  - Tris-EDTA significantly enhances antibiotic efficacy against multidrug-resistant
      Pseudomonas aeruginosa in vitro.
AB  - BACKGROUND: Multidrug-resistant Pseudomonas aeruginosa commonly complicates
      chronic bacterial otitis in dogs. HYPOTHESIS/OBJECTIVES: The aim of this in vitro
      study was to determine the effect of ethylenediaminetetraacetic acid-tromethamine
      (Tris-EDTA) on the minimal bactericidal concentrations (MBCs) and minimal
      inhibitory concentrations (MICs) of marbofloxacin and gentamicin for multidrug
      resistant P. aeruginosa isolates from cases of canine otitis. METHODS: Eleven
      isolates were identified as multidrug resistant on disc diffusion; 10 were
      resistant to marbofloxacin and two were resistant to gentamicin. Isolates were
      incubated for 90 min with each antibiotic alone and in combination with Tris-EDTA
      at concentrations of 0.075 MUg/mL to 5 mg/mL for marbofloxacin, 0.001 MUg/mL to
      10 mg/mL for gentamicin and 17.8:4.7 to 0.14:0.04 mg/mL for Tris-EDTA. Positive
      and negative controls were included. Aliquots of each antibiotic and/or Tris-EDTA
      concentration were subsequently transferred to sheep blood agar to determine the
      MBCs, and tryptone soy broth was added to the remaining suspensions to determine
      the MICs. RESULTS: Tris-EDTA alone was bacteriostatic but not bactericidal at any
      concentration. The addition of Tris-EDTA significantly reduced the median MBC
      (from 625 to 468.8 MUg/mL; P < 0.001) and MIC (from 29.3 to 2.4 MUg/mL; P =
      0.008) of marbofloxacin, and the median MBC (from 625 to 39.1 MUg/mL) and MIC
      (from 19.5 to 1.2 MUg/mL) of gentamicin (both P < 0.001). CONCLUSIONS AND
      CLINICAL IMPORTANCE: Tris-EDTA significantly reduced the MBCs and MICs of
      marbofloxacin and gentamicin for multidrug-resistant P. aeruginosa in vitro. This
      may be of use to clinicians managing these infections in dogs.

PMID- 24025022
TI  - Sodium glucose co-transporter 2 (SGLT2) inhibition with canagliflozin in type 2
      diabetes mellitus.
AB  - The sodium glucose cotransporter 2 (SGLT2) is expressed primarily in the kidneys
      and is involved in the reabsorption of filtered glucose in the renal tubule.
      Clinical trials of SGLT2 inhibitors in patients with type 2 diabetes mellitus
      demonstrate a significant clinical effect in decreasing serum glucose, hemoglobin
      A1C, body weight, systolic blood pressure, improving beta-cell function, and
      minimizing the risk of hypoglycemia. This report reviews the potentially
      beneficial effects of SGLT2 inhibitors in type 2 diabetes mellitus, specifically
      focusing on canagliflozin, the only SGLT2 inhibitor approved for use in the
      United States. 

PMID- 24025023
TI  - Synthesis, characterization, and nonvolatile ternary memory behavior of a larger
      heteroacene with nine linearly fused rings and two different heteroatoms.
AB  - To achieve ultrahigh density memory devices with the capacity of 3(n) or larger,
      organic materials with multilevel stable states are highly desirable. Here, we
      reported a novel larger stable heteroacene, 2,3,13,14-tetradecyloxy-5,11,16,22
      tetraaza-6,10,17,21-tetrachloro-7,9,18,20-tetraoxa-8,19-dicyanoenneacene (CDPzN),
      which has two different types of heteroatoms (O and N) and nine linearly fused
      rings. The sandwich-structure memory devices based on CDPzN exhibited excellent
      ternary memory behaviors with high ON2/ON1/OFF current ratios of
      10(6.3)/10(4.3)/1 and good stability for these three states. 

PMID- 24025025
TI  - Selective direct heterocoupling of alkenes catalyzed by in situ generated
      ruthenium complexes.
AB  - We describe a ruthenium-based catalytic system that allows the codimerization of
      cyclic alkenes and Michael acceptors. High yields and excellent
      stereoselectivities toward the exo-(E) adducts are obtained on a wide range of
      substrates with various functional groups. In addition, running the reaction in
      protic media leads to the reduced product resulting from the tandem
      codimerization/reduction sequence. 

PMID- 24025024
TI  - Transmitted drug resistance is still low in newly diagnosed human
      immunodeficiency virus type 1 CRF06_cpx-infected patients in Estonia in 2010.
AB  - The presence of transmitted drug resistance (TDR) in treatment-naive HIV-1
      positive subjects is of concern, especially in the countries of the former Soviet
      Union in which the number of subjects exposed to antiretrovirals (ARV) has
      exponentially increased during the past decade. We assessed the rate of TDR among
      newly diagnosed subjects in Estonia in 2010 and compared it to that in 2008. The
      study included 325 subjects (87% of all subjects tested HIV positive from January
      1 to December 31, 2010). Of the 244 sequenced viral genomic RNA in the reverse
      transcriptase (RT) region 214 were CRF06_cpx, nine were subtype A1, three (one
      each) were subtype B and subtype C, CRF02_AG, and CRF03_AB; 15 viruses remained
      unclassified as putative recombinant forms between CRF06_cpx and subtype A1. HIV
      1 TDR mutations in 2010 and 2008 (n=145) occurred at similar frequency in 4.5%
      (95% CI 2.45; 7.98) and 5.5% (95% CI 1.8; 9.24) of the patients, respectively. In
      2010, 2.5% (6/244) of the sequences harbored nonnucleoside reverse transcriptase
      inhibitor (NNRTI) (K103N and K101E), 1.6% (4/244) nucleoside reverse
      transcriptase inhibitor (NRTI) (M41L, M184I, and K219E), and 0.4% (1/244)
      protease inhibitor (PI) (V82A) mutations. Our findings indicate that in spite of
      the increased consumption of ARVs the rate of TDR in Estonia has remained
      unchanged over the past 3 years. Similar stabilizing or even decreasing trends
      have been described in Western Europe and North America albeit at higher levels
      and in different socioeconomic backgrounds.

PMID- 24025026
TI  - Comment on "Evolution of the macondo well blowout: simulating the effects of the
      circulation and synthetic dispersants on the subsea oil transport".

PMID- 24025028
TI  - Revision of a failed Swanson arthroplasty to a total wrist replacement restores
      wrist function and movements.
AB  - This study reports a case of revision of a failed Swanson silastic
      interpositional wrist replacement to a Universal 2 (KMI Medical Inc., San Diego,
      CA, Jan 2009) total wrist arthroplasty, in a 68-year-old woman with rheumatoid
      arthritis and pyrophosphate arthropathy. At the 2-year follow-up, the patient was
      pain-free and was able to perform all activities of daily living, documented by
      subjective assessment and objective scores. The disabilities of the arm,
      shoulder, and hand (DASH) scores improved from 98.3 preoperatively to 55.1
      postoperatively. A failed Swanson silastic interpositional wrist replacement may
      be successfully revised to an uncemented primary wrist replacement with good
      functional results at early follow-up.

PMID- 24025029
TI  - Self-biased solar-microbial device for sustainable hydrogen generation.
AB  - Here we demonstrate the feasibility of continuous, self-sustained hydrogen gas
      production based solely on solar light and biomass (wastewater) recycling, by
      coupling solar water splitting and microbial electrohydrogenesis in a
      photoelectrochemical cell-microbial fuel cell (PEC-MFC) hybrid device. The PEC
      device is composed of a TiO2 nanowire-arrayed photoanode and a Pt cathode. The
      MFC is an air cathode dual-chamber device, inoculated with either Shewanella
      oneidensis MR-1 (batch-fed on artificial growth medium) or natural microbial
      communities (batch-fed on local municipal wastewater). Under light illumination,
      the TiO2 photoanode provided a photovoltage of ~0.7 V that shifted the potential
      of the MFC bioanode to overcome the potential barrier for microbial
      electrohydrogenesis. As a result, under light illumination (AM 1.5G, 100
      mW/cm(2)) without external bias, and using wastewater as the energy source, we
      observed pronounced current generation as well as continuous production of
      hydrogen gas. The successful demonstration of such a self-biased, sustainable
      microbial device for hydrogen generation could provide a new solution that can
      simultaneously address the need of wastewater treatment and the increasing demand
      for clean energy.

PMID- 24025030
TI  - Botryticidal activity of nanosized silver-chitosan composite and its application
      for the control of gray mold in strawberry.
AB  - Botrytis cinerea Pers, the gray mold fungus, is among the most dangerous plant
      pathogens that cause great losses in agricultural crops. The botryticidal
      activities of nanosized silver (nano Ag), fungal chitosan (CTS) irradiated fungal
      chitosan (IrCTS), and nano Ag-IrCTS composite were investigated. All of the
      examined materials exhibited powerful antifungal activity against B. cinerea. The
      most effective compound was nano Ag-IrCTS composite with a minimal inhibitory
      concentration of 125 MUg/mL. The microscopic examination, of treated B. cinerea
      with the composite, revealed that an obvious alteration in mycelial shape was
      appeared accompanied and moderate lysis in fungal hyphae. With the prolongation
      of treatment, most of the fungal mycelia were lysed into small and elastic
      fragments. The consequence of strawberries coating, with antifungal composite
      based solution, was the disappearance of gray mold infection signs in 90% of the
      contaminated fruits after 7 d of storage, treated fruits had a fresh-like
      appearance at the end of storage. Coating with nano Ag-IrCTS solution could be
      highly recommended regarding its efficiency in prohibiting B. cinerea growth,
      preventing gray mold decay and enhancing the overall quality of coated strawberry
      fruits. 

PMID- 24025031
TI  - Life style and longevity among initially healthy middle-aged men: prospective
      cohort study.
AB  - BACKGROUND: Few studies have examined how various lifestyle factors in midlife
      predict longevity, and none of these studies have examined the impact of physical
      fitness. The present study aimed to examine longevity in relation to smoking,
      overweight and physical fitness. METHODS: We prospectively studied longevity
      (defined as reaching at least 85 years of age) in relation to smoking status,
      body mass index and physical fitness in 821 healthy men between 51 and 59 years
      of age. Of these, 369 were smokers, 320 were overweight, and 31 were obese. The
      associations were adjusted for age, systolic blood pressure and cholesterol
      level, using multivariate logistic regression analysis. Deaths were registered
      until the 31st of December, 2006. Physical fitness was measured as the total work
      performed in a maximal exercise tolerance bicycle test. RESULTS: 252 men survived
      to the age of 85 years (30.7%). Smoking status was significantly and
      independently related to longevity; 37.2% of the non-smokers survived to the age
      of 85, and 22.8% of the smokers. Among non-smokers, overweight and physical
      fitness were significantly and independently related to longevity after
      adjustment for age, blood pressure and cholesterol level, but not among smokers.
      Among non-smokers with high physical fitness, 48.8% reached the age of 85 years,
      compared to 27.9% among non-smokers with low physical fitness. CONCLUSION:
      Lifestyle variables appear to be strong and independent predictors of longevity
      in initially healthy middle-aged men. The probability of longevity may be a
      useful concept when informing the general public about the benefits of a healthy
      lifestyle.

PMID- 24025032
TI  - Quantifying transcription factor kinetics: at work or at play?
AB  - Transcription factors (TFs) interact dynamically in vivo with chromatin binding
      sites. Here we summarize and compare the four different techniques that are
      currently used to measure these kinetics in live cells, namely fluorescence
      recovery after photobleaching (FRAP), fluorescence correlation spectroscopy
      (FCS), single molecule tracking (SMT) and competition ChIP (CC). We highlight the
      principles underlying each of these approaches as well as their advantages and
      disadvantages. A comparison of data from each of these techniques raises an
      important question: do measured transcription kinetics reflect biologically
      functional interactions at specific sites (i.e. working TFs) or do they reflect
      non-specific interactions (i.e. playing TFs)? To help resolve this dilemma we
      discuss five key unresolved biological questions related to the functionality of
      transient and prolonged binding events at both specific promoter response
      elements as well as non-specific sites. In support of functionality, we review
      data suggesting that TF residence times are tightly regulated, and that this
      regulation modulates transcriptional output at single genes. We argue that in
      addition to this site-specific regulatory role, TF residence times also determine
      the fraction of promoter targets occupied within a cell thereby impacting the
      functional status of cellular gene networks. Thus, TF residence times are key
      parameters that could influence transcription in multiple ways.

PMID- 24025027
TI  - Inhibiting the HIV integration process: past, present, and the future.
AB  - HIV integrase (IN) catalyzes the insertion into the genome of the infected human
      cell of viral DNA produced by the retrotranscription process. The discovery of
      raltegravir validated the existence of the IN, which is a new target in the field
      of anti-HIV drug research. The mechanism of catalysis of IN is depicted, and the
      characteristics of the inhibitors of the catalytic site of this viral enzyme are
      reported. The role played by the resistance is elucidated, as well as the
      possibility of bypassing this problem. New approaches to block the integration
      process are depicted as future perspectives, such as development of allosteric IN
      inhibitors, dual inhibitors targeting both IN and other enzymes, inhibitors of
      enzymes that activate IN, activators of IN activity, as well as a gene therapy
      approach. 

PMID- 24025034
TI  - Blood donation clusters in Quebec, Canada (2003-2008): spatial variations
      according to sex and age.
AB  - BACKGROUND AND OBJECTIVES: The detection of spatial clusters of blood donation
      rate is an important issue, especially for targeting spatial units with
      significantly low rates, where it could be possible to increase the numbers of
      donors. The objective of this study is to detect spatial clusters of high or low
      blood donation rate in Quebec according to sex and age of the donors. MATERIALS
      AND METHODS: Blood donation data were obtained from Hema-Quebec over a period of
      5 years. We aggregated these data for each of 101 municipalites regionales de
      comte (i.e. counties) for men, women and four age groups. To detect spatial
      high/low donation rate areas, we used the Kulldorff's scan statistics. Kappa
      coefficient was used to assess discordance between clusters obtained for the
      different groups (18-29, 30-39, 40-49, 50-59, 60-69 years old). T-test analyses
      were conducted to identify significant associations between spatial clusters and
      socio-economic variables. RESULTS: The results indicate the presence of several
      geographical areas with high or low blood donation rates for each group. The
      size, the location and the socio-demographic profiles of low/high clusters vary
      according to sex and age categories. CONCLUSION: The Kulldorff's scan statistics
      are an efficient tool to assess the blood donation performance across a country
      or even a specific region over a period of several years. In terms of strategic
      planning and monitoring, it can be used as a fully operational tool to target
      areas with significantly low rates (for all donors or specific demographic
      groups) in future blood donation campaigns.

PMID- 24025035
TI  - What IJCP authors think about open access: 392 IJCP authors explain their
      preferences.

PMID- 24025033
TI  - FAST INdiCATE Trial protocol. Clinical efficacy of functional strength training
      for upper limb motor recovery early after stroke: neural correlates and
      prognostic indicators.
AB  - RATIONALE: Functional strength training in addition to conventional physical
      therapy could enhance upper limb recovery early after stroke more than movement
      performance therapy plus conventional physical therapy. AIMS: To determine (a)
      the relative clinical efficacy of conventional physical therapy combined with
      functional strength training and conventional physical therapy combined with
      movement performance therapy for upper limb recovery; (b) the neural correlates
      of response to conventional physical therapy combined with functional strength
      training and conventional physical therapy combined with movement performance
      therapy; (c) whether any one or combination of baseline measures predict motor
      improvement in response to conventional physical therapy combined with functional
      strength training or conventional physical therapy combined with movement
      performance therapy. DESIGN: Randomized, controlled, observer-blind trial. STUDY:
      The sample will consist of 288 participants with upper limb paresis resulting
      from a stroke that occurred within the previous 60 days. All will be allocated to
      conventional physical therapy combined with functional strength training or
      conventional physical therapy combined with movement performance therapy.
      Functional strength training and movement performance therapy will be undertaken
      for up to 1.5 h/day, five-days/week for six-weeks. OUTCOMES AND ANALYSIS:
      Measurements will be undertaken before randomization, six-weeks thereafter, and
      six-months after stroke. Primary efficacy outcome will be the Action Research Arm
      Test. Explanatory measurements will include voxel-wise estimates of brain
      activity during hand movement, brain white matter integrity (fractional
      anisotropy), and brain-muscle connectivity (e.g. latency of motor evoked
      potentials). The primary clinical efficacy analysis will compare treatment groups
      using a multilevel normal linear model adjusting for stratification variables and
      for which therapist administered the treatment. Effect of conventional physical
      therapy combined with functional strength training versus conventional physical
      therapy combined with movement performance therapy will be summarized using the
      adjusted mean difference and 95% confidence interval. To identify the neural
      correlates of improvement in both groups, we will investigate associations
      between change from baseline in clinical outcomes and each explanatory measure.
      To identify baseline measurements that independently predict motor improvement,
      we will develop a multiple regression model.

PMID- 24025036
TI  - Comment on "protective arms of the renin-angiotensin system in neurological
      disease".

PMID- 24025038
TI  - The impact of next generation sequencing on the analysis of breast cancer
      susceptibility: a role for extremely rare genetic variation?
AB  - Women with a family history of breast cancer have an approximately twofold
      elevated risk of the disease. Even though an array of genes has been associated
      with breast cancer risk the past two decades, variants within these genes jointly
      explain at most 40% of this familial risk. Many explanations for this 'missing
      heritability' have been proposed, including the existence of many very rare
      variants, interactions between genetic and environmental factors and structural
      genetic variation. In this review, we discuss how next generation sequencing will
      teach us more about the genetic architecture of breast cancer, with a specific
      focus on very rare genetic variants. While such variants potentially explain a
      substantial proportion of familial breast cancer, assessing the breast cancer
      risks conferred by them remains challenging, even if this risk is relatively
      high. To assess more moderate risks, epidemiological approaches will require very
      large patient cohorts to be genotyped for the variant, only achievable through
      international collaboration. How well we will be able to eventually resolve the
      missing heritability for breast cancer in a clinically meaningful way crucially
      depends on the underlying complexity of the genetic architecture. 

PMID- 24025037
TI  - Analysis of Phakopsora pachyrhizi transcript abundance in critical pathways at
      four time-points during infection of a susceptible soybean cultivar using deep
      sequencing.
AB  - BACKGROUND: Phakopsora pachyrhizi, the causal agent responsible for soybean rust,
      is among the top hundred most virulent plant pathogens and can cause soybean
      yield losses of up to 80% when appropriate conditions are met. We used mRNA-Seq
      by Illumina to analyze pathogen transcript abundance at 15 seconds (s), 7 hours
      (h), 48 h, and 10 days (d) after inoculation (ai) of susceptible soybean leaves
      with P. pachyrhizi to gain new insights into transcript abundance in soybean and
      the pathogen at specific time-points during the infection including the uredinial
      stage. RESULTS: Over three million five hundred thousand sequences were obtained
      for each time-point. Energy, nucleotide metabolism, and protein synthesis are
      major priorities for the fungus during infection and development as indicated by
      our transcript abundance studies. At all time-points, energy production is a
      necessity for P. pachyrhizi, as indicated by expression of many transcripts
      encoding enzymes involved in oxidative phosphorylation and carbohydrate
      metabolism (glycolysis, glyoxylate and dicarboxylate, pentose phosphate,
      pyruvate). However, at 15 sai, transcripts encoding enzymes involved in ATP
      production were highly abundant in order to provide enough energy for the spore
      to germinate, as observed by the expression of many transcripts encoding proteins
      involved in electron transport. At this early time-point, transcripts encoding
      proteins involved in RNA synthesis were also highly abundant, more so than
      transcripts encoding genes involved in DNA and protein synthesis. At 7 hai,
      shortly after germination during tube elongation and penetration, transcripts
      encoding enzymes involved in deoxyribonucleotide and DNA synthesis were highly
      abundant. At 48 hai, transcripts encoding enzymes involved in amino acid
      metabolism were highly abundant to provide for increased protein synthesis during
      haustoria maturation. During sporulation at 10 dai, the fungus still required
      carbohydrate metabolism, but there also was increased expression of transcripts
      encoding enzymes involved in fatty acid metabolism. CONCLUSION: This information
      provides insight into molecular events and their timing throughout the life cycle
      of the P. pachyrhizi, and it may be useful in the development of new methods of
      broadening resistance of soybean to soybean rust.

PMID- 24025039
TI  - The fetal splenic vein flow pattern and fetal inflammatory response in the
      preterm prelabor rupture of membranes.
AB  - OBJECTIVE: To evaluate the intensity of the fetal inflammatory response,
      characterized by umbilical cord blood IL-6 levels, and neonatal outcome in the
      preterm prelabor rupture of membranes (PPROM) pregnancies using the pulsatile
      fetal splenic vein flow pattern. METHODS: Women with singleton pregnancies
      complicated by PPROM at a gestational age between 24 + 0 and 36 + 6 weeks were
      included in the study. Doppler evaluation of the fetal splenic vein flow was
      performed. The flow-velocity waveform pattern was evaluated qualitatively as
      continuous or pulsatile. The umbilical cord blood interleukin-6 (IL-6) levels
      were evaluated after delivery. The fetal inflammatory response was defined as IL
      6 >11 pg/mL. RESULTS: In total, 129 women were included. The fetuses with
      pulsatile splenic vein flow exhibited higher IL-6 levels in umbilical cord blood
      (median: 56.7 pg/mL versus 5.6 pg/mL; p < 0.0001) and had a higher rate of fetal
      inflammatory response syndrome (71% versus 35%; p = 0.0005) than fetuses with
      continuous flow. The pulsatile flow pattern was related to a higher rate of early
      onset neonatal sepsis (odds ratio 4.2; 95% confidence interval: 1.3-13.5).
      CONCLUSION: The presence of pulsatile fetal splenic vein flow in PPROM
      pregnancies is associated with fetal inflammatory response and neonatal
      morbidity.

PMID- 24025040
TI  - Rejection after conversion to a proliferation signal inhibitor in chronic heart
      transplantation.
AB  - We sought to determine the incidence, risk factors, and consequences of acute
      rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a
      proliferation signal inhibitor (PSI) in maintenance heart transplantation.
      Relevant clinical data were retrospectively obtained for 284 long-term heart
      transplant recipients from nine centers in whom CNIs were replaced with a PSI
      (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate
      at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate
      after conversion (4.9 per 100 patient-years) was significantly higher than that
      observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years).
      By multivariate analysis, rejection risk was associated with a history of late AR
      prior to PSI conversion, early conversion (<5 yr) after transplantation and age
      <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective
      factor. Post-conversion rejection did not significantly influence the evolution
      of left ventricular ejection fraction, renal function, or mortality during
      further follow-up. Conversion to a CNI-free immunosuppression based on a PSI
      results in an increased risk of AR. Awareness of the clinical determinants of
      post-conversion rejection could help to refine the current PSI conversion
      strategies.

PMID- 24025041
TI  - Cellular HIV type 1 DNA levels are equivalent among drug-sensitive and drug
      resistant strains in newly diagnosed and antiretroviral naive patients.
AB  - The emergence of resistance against current antiretroviral drugs to human
      immunodeficiency virus type 1 (HIV-1) is an increasingly important concern to the
      continuous success of antiretroviral therapy to HIV-1-infected patients. In the
      past decade, a number of studies reported that the prevalence of transmitted drug
      resistance among newly diagnosed patients has reached an overall 9% prevalence
      worldwide. Also, a number of studies using longitudinal HIV-1 patient study
      cohorts demonstrated that the cellular HIV-1 DNA level in peripheral blood
      mononuclear cells (PBMCs) has a prognostic value for the progression of HIV-1
      disease independently of plasma HIV-1 RNA load and CD4 count. Using a previously
      established molecular-beacon-based real-time PCR methodology, cellular HIV-1 DNA
      levels were quantified in newly diagnosed and antiretroviral-naive patients in
      Northern Greece recruited between 2009 and 2010 using a predefined enrolling
      strategy, in an effort to investigate whether there is any relationship between
      cellular HIV-1 DNA levels and HIV-1 transmitted drug resistance. As part of the
      same study, DNA sequences encoding the env (C2-C5 region of gp120) were also
      amplified from PBMC-extracted DNA in order to determine the genotypic coreceptor
      tropism and genetic subtype. Cellular HIV-1 DNA levels had a median of 3.309
      log10 HIV-1 copies per 10(6) PBMCs and demonstrated no correlation between
      cellular HIV-1 DNA levels and HIV-1 transmitted drug resistance. An absence of
      association between cellular HIV-1 DNA levels with plasma viral HIV-1 RNA load
      and CD4 levels was also found reconfirming the previously published study.
      Genotypic analysis of coreceptor tropism indicated that 96% of samples,
      independently of the presence or not of genotypic drug resistance, were CCR5
      tropic. Overall, the findings reconfirmed the previously proposed proposition
      that transmitted drug resistance does not have an impact on disease progression
      in HIV-1-infected individuals. Also, CCR5 coreceptor tropism dominance suggests
      that both drug-resistant and drug-sensitive strains behave similarly in early
      infection in newly diagnosed patients.

PMID- 24025042
TI  - Progression of periodontal inflammation in adolescents is associated with
      increased number of Porphyromonas gingivalis, Prevotella intermedia, Tannerella
      forsythensis, and Fusobacterium nucleatum.
AB  - OBJECTIVE: The study aims to evaluate the change of related subgingival
      periodontopathogens among different stage of gingivitis in adolescent and assess
      the relationship between periodontopathogens and the progression of periodontal
      inflammation. METHODS: A total of 77 subgingival plaque samples from 35
      adolescent individuals were divided into three groups including gingivitis group
      (mild, 15 samples; moderate, 16 samples; severe, 15 samples), chronic
      periodontitis group (15 samples) and healthy group (15 samples). Real-time PCR
      was used to quantitate Porphyromonas gingivalis, Prevotella intermedia,
      Tannerella forsythensis, and Fusobacterium nucleatum in subgingival plaque
      samples. RESULTS: All species, except for F. nucleatum, were detected in samples
      from gingivitis and periodontitis groups in significantly greater number than in
      those from healthy group (P < 0.05). In gingivitis groups, the number of P.
      gingivalis, T. forsythensis, and F. nucleatum in moderate and severe gingivitis
      groups was significantly higher than in mild gingivitis group (P < 0.05). After
      merging moderate gingivitis and severe gingivitis groups into moderate-to-severe
      gingivitis group, the four periodontopathogens were detected in samples from
      periodontitis group in significantly greater number than in those from moderate
      to-severe gingivitis group (P < 0.05). CONCLUSION: The number of P. gingivalis,
      P. intermedia, T. forsythensis, and F. nucleatum in subgingival plaque increases
      with progression of periodontal inflammation in adolescents. Examination of
      periodontopathogens number in adolescents may be of some value for monitoring of
      periodontal disease development.

PMID- 24025043
TI  - Bis(carbazolyl)ureas as selective receptors for the recognition of
      hydrogenpyrophosphate in aqueous media.
AB  - Recognition properties of the novel bis(carbazole) tris-ureidic-based receptors 1
      and 2 toward different anions have been studied by (1)H NMR and absorption and
      emission spectroscopy, as well as by DFT calculations. Receptor 1, in which the
      two urea-functionalized arms are decorated with p-nitrophenyl rings, behaves as a
      highly selective chromogenic molecular probe for hydrogenpyrophosphate anion in a
      competitive medium (acetonitrile/water, 70/30). Receptor 2, bearing two urea arms
      decorated with photoactive pyrenyl rings, acts as a highly selective fluorescent
      molecular probe for hydrogenpyrophosphate anion in either acetonitrile or an
      aqueous mixture (acetonitrile/water, 85/15). Receptor 2 exhibits a dual monomer
      excimer emission spectrum and undergoes a remarked ratiometry in acetonitrile in
      the presence of hydrogenpyrophosphate: the excimer band disappears, whereas the
      monomer band is slightly increased. However, in the aqueous mixture, a strong
      increase of the excimer emission band was observed, while the monomer emission
      bands remained almost unaffected. The resulting binding modes and spectroscopic
      features are explained by suitable structures of model complexes for both
      receptors. In such complexes, a peripheral cooperative effect was found,
      alleviating the excess of negative charge in the guest toward the outer surface
      of the host, as well as the required enlargement on its internal cavity. 

PMID- 24025044
TI  - Sensory evaluation of dry-fermented sausage containing ground deodorized yellow
      mustard.
AB  - Ground deodorized yellow mustard is used as a binder and meat protein substitute
      in cooked processed meat products. Recent studies have shown that it has the
      potential to be used in uncooked processed meat products because of its natural
      antimicrobial properties. In the present study, ground deodorized yellow mustard
      was added to uncooked dry-fermented sausage during manufacture at 1% to 4% (w/w)
      and analyzed for its effects on starter cultures, physico-chemical properties,
      and consumer acceptability. Mustard had a nondose-dependent inhibitory effect on
      the Staphylococcus starter culture, had no effect on water activity or
      instrumental texture, and tended to accelerate sausage pH reduction. At 3% and 4%
      mustard, consumer scores on all sensory attributes as well as overall
      acceptability were significantly lower. The appearance and color of 3% and 4%
      mustard-treated sausages were liked slightly, whereas flavor, texture, and
      overall acceptability scores were reduced. The control without mustard and 1%
      mustard-treated sausages had similar sensory properties and were the most
      acceptable, while 2% mustard-treated sausages were given "like moderately" and
      "like slightly" descriptors. Sensory results mean that at concentrations
      necessary for mandated regulatory control of Escherichia coli O157:H7 in dry
      sausages, mustard may have a negative effect on consumer acceptance. 

PMID- 24025045
TI  - Copper-catalyzed B-H bond insertion reaction: a highly efficient and
      enantioselective C-B bond-forming reaction with amine-borane and phosphine-borane
      adducts.
AB  - A copper-catalyzed B-H bond insertion reaction with amine- and phosphine-borane
      adducts was realized with high yield and enantioselectivity under mild reaction
      conditions. The B-H bond insertion reaction provides a new C-B bond-forming
      methodology and an efficient approach to chiral organoboron compounds. 

PMID- 24025046
TI  - Mapping the global journey of anthropogenic aluminum: a trade-linked multilevel
      material flow analysis.
AB  - Material cycles have become increasingly coupled and interconnected in a
      globalizing era. While material flow analysis (MFA) has been widely used to
      characterize stocks and flows along technological life cycle within a specific
      geographical area, trade networks among individual cycles have remained largely
      unexplored. Here we developed a trade-linked multilevel MFA model to map the
      contemporary global journey of anthropogenic aluminum. We demonstrate that the
      anthropogenic aluminum cycle depends substantially on international trade of
      aluminum in all forms and becomes highly interconnected in nature. While the
      Southern hemisphere is the main primary resource supplier, aluminum production
      and consumption concentrate in the Northern hemisphere, where we also find the
      largest potential for recycling. The more developed countries tend to have a
      substantial and increasing presence throughout the stages after bauxite refining
      and possess highly consumption-based cycles, thus maintaining advantages both
      economically and environmentally. A small group of countries plays a key role in
      the global redistribution of aluminum and in the connectivity of the network,
      which may render some countries vulnerable to supply disruption. The model
      provides potential insights to inform government and industry policies in
      resource criticality, supply chain security, value chain management, and cross
      boundary environmental impacts mitigation. 

PMID- 24025047
TI  - Plasmon-enhanced enzyme-linked immunosorbent assay on large arrays of individual
      particles made by electron beam lithography.
AB  - Ultrasensitive biosensing is one of the main driving forces behind the dynamic
      research field of plasmonics. We have previously demonstrated that the
      sensitivity of single nanoparticle plasmon spectroscopy can be greatly enhanced
      by enzymatic amplification of the refractive index footprint of individual
      protein molecules, so-called plasmon-enhanced enzyme-linked immunosorbent assay
      (ELISA). The technique, which is based on generation of an optically dense
      precipitate catalyzed by horseradish peroxidase at the metal surface, allowed for
      colorimetric analysis of ultralow molecular surface coverages with a limit of
      detection approaching the single molecule limit. However, the plasmonic response
      induced by a single enzyme can be expected to vary for a number of reasons,
      including inhomogeneous broadening of the sensing properties of individual
      particles, variation in electric field enhancement over the surface of a single
      particle and variation in size and morphology of the enzymatic precipitate. In
      this report, we discuss how such inhomogeneities affect the possibility to
      quantify the number of molecules bound to a single nanoparticle. The discussion
      is based on simulations and measurements of large arrays of well-separated gold
      nanoparticles fabricated by electron beam lithography (EBL). The new data
      confirms the intrinsic single-molecule sensitivity of the technique but we were
      not able to clearly resolve the exact number of adsorbed molecules per single
      particle. The results indicate that the main sources of uncertainty come from
      variations in sensitivity across the surface of individual particles and between
      different particles. There is also a considerable uncertainty in the actual
      precipitate morphology produced by individual enzyme molecules. Possible routes
      toward further improvements of the methodology are discussed. 

PMID- 24025048
TI  - Can high-risk fungicides be used in mixtures without selecting for fungicide
      resistance?
AB  - Fungicide mixtures produced by the agrochemical industry often contain low-risk
      fungicides, to which fungal pathogens are fully sensitive, together with high
      risk fungicides known to be prone to fungicide resistance. Can these mixtures
      provide adequate disease control while minimizing the risk for the development of
      resistance? We present a population dynamics model to address this question. We
      found that the fitness cost of resistance is a crucial parameter to determine the
      outcome of competition between the sensitive and resistant pathogen strains and
      to assess the usefulness of a mixture. If fitness costs are absent, then the use
      of the high-risk fungicide in a mixture selects for resistance and the fungicide
      eventually becomes nonfunctional. If there is a cost of resistance, then an
      optimal ratio of fungicides in the mixture can be found, at which selection for
      resistance is expected to vanish and the level of disease control can be
      optimized.

PMID- 24025049
TI  - Host plant resistance against tomato spotted wilt virus in peanut (Arachis
      hypogaea) and its impact on susceptibility to the virus, virus population
      genetics, and vector feeding behavior and survival.
AB  - Tomato spotted wilt virus (TSWV) severely affects peanut production in the
      southeastern United States. Breeding efforts over the last three decades resulted
      in the release of numerous peanut genotypes with field resistance to TSWV. The
      degree of field resistance in these genotypes has steadily increased over time,
      with recently released genotypes exhibiting a higher degree of field resistance
      than older genotypes. However, most new genotypes have never been evaluated in
      the greenhouse or laboratory against TSWV or thrips, and the mechanism of
      resistance is unknown. In this study, TSWV-resistant and -susceptible genotypes
      were subjected to TSWV mechanical inoculation. The incidence of TSWV infection
      was 71.7 to 87.2%. Estimation of TSWV nucleocapsid (N) gene copies did not reveal
      significant differences between resistant and susceptible genotypes. Parsimony
      and principal component analyses of N gene nucleotide sequences revealed
      inconsistent differences between virus isolates collected from resistant and
      susceptible genotypes and between old (collected in 1998) and new (2010)
      isolates. Amino acid sequence analyses indicated consistent differences between
      old and new isolates. In addition, we found evidence for overabundance of
      nonsynonymous substitutions. However, there was no evidence for positive
      selection. Purifying selection, population expansion, and differentiation seem to
      have influenced the TSWV populations temporally rather than positive selection
      induced by host resistance. Choice and no-choice tests indicated that resistant
      and susceptible genotypes differentially affected thrips feeding and survival.
      Thrips feeding and survival were suppressed on some resistant genotypes compared
      with susceptible genotypes. These findings reveal how TSWV resistance in peanut
      could influence evolution, epidemiology, and management of TSWV.

PMID- 24025050
TI  - Progression of pectinate ligament dysplasia over time in two populations of Flat
      Coated Retrievers.
AB  - OBJECTIVE: Two of the authors (DG, BS) independently observed that a number of
      Flat-Coated Retrievers (FCRs) previously unaffected by pectinate ligament
      dysplasia (PLD) appeared to develop the condition later in life. This study was
      instigated to investigate progression of PLD within individual dogs over time.
      ANIMALS STUDIED: Flat-Coated Retrievers that had previously undergone gonioscopy
      under the UK/ECVO hereditary eye schemes were included in the study. PROCEDURE: A
      second gonioscopic examination was performed 1.92-12.58 years later (mean 6,
      median 5.75 years) and the results compared. 39 FCR (17 males, 22 females) in the
      UK and 57 FCR (27 males, 30 females) in Switzerland were included. Slit-lamp
      biomicroscopy, indirect ophthalmoscopy, and gonioscopy were performed in all
      dogs. Gonioscopy allowed classification as either unaffected or affected;
      percentage of the iridocorneal drainage angle (ICA) affected by PLD was
      determined, before calculating progression observed as mild, moderate, or severe.
      RESULTS: 39 of 96 (40.6%) dogs demonstrated progression of PLD (P < 0.0001). Of
      these, 13 of 96 (13.5%) were classified as mild progression (from either
      unaffected to 10-20% or 10-20% to 20-90% ICA affected). Progression was more
      extensive in 26 of 96 (27.1%) dogs (P < 0.0001), of which 12 of 96 (12.5%) went
      from unaffected to severe PLD of >90% ICA affected, consistent with a high risk
      of glaucoma. CONCLUSIONS: To the authors' knowledge, this is the first report
      describing progression of PLD in individual dogs over time, in a breed affected
      by primary, angle closure glaucoma.

PMID- 24025051
TI  - Conventional and novel diagnostic biomarkers of acute myocardial infarction: a
      promising role for circulating microRNAs.
AB  - Biomarkers play a critical role in the diagnosis of acute myocardial infarction
      (AMI), especially in patients with atypical clinical and/or electrocardiographic
      presentation or co-morbidities, like the elderly. High-sensitivity assays based
      on specific biomarkers (e.g. cardiac troponins) enabling earlier AMI diagnosis
      have recently become available in clinical practice. Although no single biomarker
      of myocardial necrosis is ever likely to afford AMI diagnosis, a combination
      including different biomarkers for necrosis and ischemia, like new circulating
      molecules (microRNAs), could enhance diagnostic specificity. We review the recent
      literature on conventional and novel AMI biomarkers, with special emphasis on
      circulating microRNAs.

PMID- 24025053
TI  - Editorial: disorders of consciousness: recent advances in neurobiology and
      treatments.

PMID- 24025054
TI  - Pharmacological modulation of the state of awareness in patients with disorders
      of consciousness: an overview.
AB  - The neurobiological approach to consciousness moves from the assumption that all
      phenomenal experiences are based on neuronal activity in the brain. Consciousness
      has two main components: wakefulness and awareness. While it may be relatively
      easy to determine the neuronal correlates of wakefulness, it is not the same for
      awareness, of which the neural correlates are poorly understood. Knowledge of the
      circuitry and the neurochemistry of the sleep/wake condition is necessary but not
      sufficient to understand the circuitry and neurochemistry of consciousness.
      Disorders of consciousness (DOCs) include coma, vegetative state and minimally
      conscious state. The study of DOCs and of the electrophysiological changes
      underlying general anaesthesia-induced loss of consciousness may help in
      understanding the neuronal correlates of consciousness. In turn, the
      understanding of the neural bases of consciousness may help in designing
      interventions aimed at restoring consciousness in DOC patients. Sporadic cases of
      recovery from a DOC have been reported after the administration of various
      pharmacological agents (baclofen, zolpidem, amantadine etc.). This review
      provides an overview of such drugs, which are from various and diverging classes
      but can be grouped into two main categories: CNS stimulants and CNS depressants.
      The available data seem to suggest an awakening effect obtained with CNS
      depressants rather than stimulants, the latter being more effective at improving
      functional cognitive and behavioral recovery in patients who have spontaneously
      regained an appreciable level of consciousness. There is a need for more rigorous
      systematic trials and further investigation of the above treatments, with
      particular attention paid to their mechanisms of action and the neurotransmitters
      involved. 

PMID- 24025055
TI  - Neurobiological influences on recovery from traumatic brain injury: the role of
      genetic polymorphisms.
AB  - Recovery from traumatic brain injury (TBI) is variable despite similarities in
      the severity or mechanism of injury. The study of genetic polymorphisms offers an
      avenue for explaining individual differences in recovery and outcome following
      TBI. The current paper reviews the role that genetic polymorphisms may play in
      influencing recovery and quality of life following TBI. Investigating the role of
      polymorphisms on recovery from TBI may contribute to a better understanding of
      individual variations in outcome and has the potential to lead to earlier and
      more targeted interventions and rehabilitation based on a patient's genetic
      makeup. By outlining what has been discovered about the relationship between
      polymorphisms and TBI we hope to both inform the medical community about the
      potential for polymorphisms to influence recovery following TBI and provide a
      roadmap to researchers about the gaps in research within this population. 

PMID- 24025056
TI  - Disorders of consciousness and pharmaceuticals that act on oxygen based amino
      acid and monoamine neurotransmitter pathways of the brain.
AB  - Oxygen based neurotransmitters in the synapses of the brain are proposed to play
      an important role in the generation of consciousness. They include the amino
      acids glutamate and GABA which use Krebs cycle precursors for their synthesis,
      and the monoamines dopamine, noradrenalin, adrenalin and serotonin, which are
      derived from tyrosine and tryptophan. During ischemia after an acute brain
      injury, a GABA surge often initiates brain suppression. It has been proposed that
      with chronic ischemia, a secondary, possibly epigenetic response occurs when
      neurotransmitters deplete, a glucose and oxygen saving mechanism termed
      neurodormancy that may invoke alternative long term low energy metabolic pathways
      in the brain, encountered in Disorders of Consciousness. Some medications can
      reverse Disorders of Consciousness in some patients. Virtually all of them act on
      neurotransmitter systems that use oxygen as a building block or as an energy
      source within the brain. Pharmaceuticals that act in the oxygen based amino acid
      systems of the brain include the GABAergic medications zolpidem and baclofen,
      while those that act in the monoamine axes include the dopaminergic medications L
      Dopa, amantadine, bromocriptine, apomorphine and methylphenidate, and the
      noradrenergic and serotonergic medications desipramine, amitriptyline,
      protriptyline and fluoxetine. Another group are the cholinesterase inhibitors,
      responsible for increasing acetylcholine, which is synthesized from the Krebs
      cycle initiator, acetyl CoA. It appears that pharmaceuticals that are active in
      the oxygen based neurotransmitter pathways of the brain are successful to arouse
      to consciousness patients that suffer from its disorders. Research needs to be
      supported as foundation to understand the biochemical mechanisms that are
      involved in consciousness disorders and to explore further the pharmacological
      treatment possibilities for these devastating neurological conditions. 

PMID- 24025052
TI  - Bridge between neuroimmunity and traumatic brain injury.
AB  - The pathophysiology of degenerative, infectious, inflammatory and traumatic
      diseases of the central nervous system includes a significant immune component.
      As to the latter, damage to the cerebral vasculature and neural cell bodies,
      caused by traumatic brain injury (TBI) activates innate immunity with concomitant
      infiltration of immunocytes into the damaged nervous system. This leads to
      proinflammatory cytokine and prostaglandin production and lost synaptic integrity
      and more generalized neurotoxicity. Engagement of adaptive immune responses
      follows including the production of antibodies and lymphocyte proliferation.
      These affect the tempo of disease along with tissue repair and as such provide a
      number of potential targets for pharmacological treatments for TBI. However,
      despite a large body of research, no such treatment intervention is currently
      available. In this review we will discuss the immune response initiated following
      brain injuries, drawing on knowledge gained from a broad array of experimental
      and clinical studies. Our discussion seeks to address potential therapeutic
      targets and propose ways in which the immune system can be controlled to promote
      neuroprotection. 

PMID- 24025057
TI  - Amantadine, apomorphine and zolpidem in the treatment of disorders of
      consciousness.
AB  - Survivors of severe brain injuries may end up in a state of 'wakeful
      unresponsiveness' or in a minimally conscious state. Pharmacological treatments
      of patients with disorders of consciousness aim to improve arousal levels and
      recovery of consciousness. We here provide a systematic overview of the
      therapeutic effects of amantadine, apomorphine and zolpidem in patients
      recovering from coma. Evidence from clinical trials using these commonly
      prescribed pharmacological agents suggests positive changes of the patients'
      neurological status, leading sometimes to dramatic improvements. These findings
      are discussed in the context of current hypotheses of these agents' therapeutic
      mechanisms on cerebral function. In order to improve our understanding of the
      underlying pathophysiological mechanisms of these drugs, we suggest combining
      sensitive and specific behavioral tools with neuroimaging and
      electrophysiological measures in large randomized, double-blind, placebo
      controlled experimental designs. We conclude that the pharmacokinetics and
      pharmacodynamics of amantadine, apomorphine and zolpidem need further exploration
      to determine which treatment would provide a better neurological outcome
      regarding the patient's etiology, diagnosis, time since injury and overall
      condition. 

PMID- 24025058
TI  - General anesthetics in brain injury: friends or foes?
AB  - General anesthesia-induced pharmacological protection of the central nervous
      system following injury has been under intense investigations during the past
      four decades. Indeed, if general anesthetics could provide therapeutic benefit in
      the event of hypoxia, ischemia or any other kinds of brain lesions, that would be
      of tremendous clinical importance. The potential for anesthesia-related brain
      protection, however, has been seriously challenged during the past 10 years. In
      fact, an increasing number of experimental and, more recently, clinical
      observations suggest that general anesthetics might exert unwanted, toxic effects
      on the brain especially when administered to young infants or to the elderly. Of
      utmost importance, recent data suggest that these same drugs could even have
      therapeutic effects in some psychiatric disorders. The goal of this review is to
      highlight these apparent contradictions. We will consider the available
      experimental evidence arguing for anesthetic-induced neuroprotection and
      highlight the lack of clinical studies supporting this notion. The biological
      rational for anesthesia neurotoxicity will then be explored together with
      existing experimental and clinical evidence in favor of this possibility.
      Finally, insights into the increasing number of both experimental and clinical
      data suggesting that general anesthetics, especially ketamine, support the
      therapeutic value of these drugs in major depressive disorders. When taken
      together, these seemingly contradictory observations suggest the intriguing
      possibility that general anesthetics could stand as valuable context-dependent
      modulators of neural plasticity. 

PMID- 24025059
TI  - Restoring cortical connectivity directionality and synchronization is essential
      to treating disorder of consciousness.
AB  - The design of neurorehabilitation therapy to treat subjects with altered
      consciousness provides opportunities and challenges to professionals involved
      with the care for these severely ill patients. While there is an increased
      interest in determining methods to restore consciousness in these patients, the
      process is complex and challenging, due in part to the diverse aetiology of these
      states of consciousness, and also to the intricate cerebral connectivity involved
      in their treatment. The present case study examines a patient who showed signs of
      emergence from the vegetative state after neurorehabilitation using The Combined
      Method Therapy (CMT). In this case, neurorehabilitation therapy was applied
      simultaneously with pharmacological treatment, stimulation, and neuroimaging
      techniques to help adjust drug dosage. The results of this study suggest that
      this combined approach to treatment promoted connectivity among posterior and
      anterior cortical regions aiding emergence from the vegetative state. 

PMID- 24025060
TI  - Harnessing anesthesia and brain imaging for the study of human consciousness.
AB  - Philosophers have been trying to solve the mind-body problem for hundreds of
      years. Consciousness is the core of this problem: How do subjective conscious
      sensations, perceptions, feelings, and thoughts arise out of objective physical
      brain activities? How is this subjective conscious world in causal interaction
      with the objective sensory and motor mechanisms of the brain and the body?
      Although we witness the seamless interaction of the mental and the physical
      worlds in our everyday lives, no scientific theory can yet fully describe or
      explain it. The hard problem of consciousness, the question why and how any brain
      activity should be accompanied by any subjective experiences at all, remains a
      mystery and a challenge for modern science. Anesthesia offers a unique and safe
      way to directly manipulate the state of consciousness and can, thus, be used as a
      tool in consciousness research. With neuroimaging, such as positron emission
      tomography (PET) and functional magnetic resonance imaging (fMRI) performed at
      different states of consciousness, it is possible to visualize the state-related
      changes and pinpoint the brain structures or neural mechanisms related to changes
      in consciousness. With these tools, neurosciences now show promise in
      disentangling the eternal enigma of human consciousness. In this article, we will
      review the recent advancements in the field. 

PMID- 24025061
TI  - Disorders of consciousness and electrophysiological treatment strategies: a
      review of the literature and new perspectives.
AB  - The last years have witnessed a significant increase in our understanding of
      brain functions in survivors of severe brain injuries with disorders of
      consciousness (DOC). Despite there is currently no effective standardized
      treatment for DOC patients, in the past decade many potential pharmacological as
      well as non-pharmacological therapies have been proposed. A promising and
      increasingly growing field of non-pharmacological therapeutic trials has been
      supported by the application of electrophysiological techniques. This article
      reviews the most relevant studies in the literature in order to provide the
      reader with a clear picture of the current available neurophysiological
      instruments that could be used to treat DOC patients. We will hereinafter briefly
      discuss the basic principles of deep brain stimulation (DBS), repetitive
      transcranial magnetic stimulation (rTMS), spinal cord stimulation (SCS) and
      peripheral nerve stimulation (MNS) that are the main techniques now used by
      researchers as a treatment and we will explain the rationale of these therapies.
      Then, we will outline the more relevant studies regarding their application in
      DOC patients. Finally, due to the fact that only a moderate amount of individual
      or clinically-dependent approaches are available, we conclude that more
      standardized studies are necessary to address the role of electrophysiological
      treatment strategies in DOC as well as to further elucidate their therapeutic
      effects and define optimal stimulation parameters. Undoubtedly, at present the
      multidimensional approach is the most interesting. 

PMID- 24025062
TI  - Mechanisms of cortical neural synchronization related to healthy and impaired
      consciousness: evidence by quantitative electroencephalographic studies.
AB  - In this paper, we review the contribution of our research group to the study of
      human consciousness by quantitative electroencephalographic (EEG) techniques. We
      posit that EEG techniques can be extremely useful for a direct measurement of
      brain electrophysiological activity related to human consciousness for their
      unsurpassable high temporal resolution (milliseconds). This activity can be
      expressed in terms of event-related potentials as well as changes of EEG rhythms
      of interest, for example the dominant alpha rhythms (about 8-12 Hz). The results
      of our studies, and those of several independent groups, lead support to the
      hypothesis that these techniques provide important insights about the
      neurophysiologic mechanisms underlying cortical neural
      synchronization/desynchronization and the regulation of neuromodulatory systems
      (e.g. dopaminergic, noradrenergic, cholinergic, etc.) at the basis of brain
      arousal and consciousness in healthy subjects and in patients with impairment of
      the consciousness. A possible interaction of these mechanisms and the drugs
      administered to patients with consciousness disorders is discussed. 

PMID- 24025063
TI  - Zolpidem arousing effect in persistent vegetative state patients: autonomic, EEG
      and behavioral assessment.
AB  - OBJECTIVE: To study the Zolpidem arousing effect in persistent vegetative state
      (PVS) patients combining clinical evaluation, autonomic assessment by heart rate
      variability (HRV), and EEG records. METHODS: We studied a group of 8 PVS patients
      and other 8 healthy control subjects, matched by age and gender. The patients and
      controls received drug or placebo in two experimental sessions, separated by 10
      14 days. The first 30 minutes of the session were considered the basal record,
      and then Zolpidem was administered. All participants were evaluated clinically,
      by EEG, and by HRV during the basal record, and for 90 minutes after drug intake.
      RESULTS: We found in all patients, time-related arousing signs after Zolpidem
      intake: behavioral (yawns and hiccups), activation of EEG cortical activity, and
      a vagolytic chronotropic effect without a significant increment of the vasomotor
      sympathetic tone. CONCLUSIONS: We demonstrated time-related arousing signs after
      Zolpidem intake. We discussed possible mechanisms to explain these patho
      physiological findings regarding EEG cortical activation and an autonomic
      vagolytic drug effect. As this autonomic imbalance might induce cardiocirculatory
      complications, which we didn't find in any of our patients, we suggest developing
      future trials under control of physiological indices by bedside monitoring.
      However, considering that this arousing Zolpidem effect might be certainly
      related to brain function improvement, it should be particularly considered for
      the development of new neuro-rehabilitation programs in PVS cases. According to
      the literature review, we claim that this is the first report about the vagolitic
      effect of Zolpidem in PVS cases.

PMID- 24025064
TI  - True or false? Activations of language-related areas in patients with disorders
      of consciousness.
AB  - Twenty-nine patients with Unresponsive Wakefulness Syndrome (UWS), 26 patients in
      Minimally Conscious State (MCS), and 21 healthy control individuals matched in
      age and social environment (patients' relatives) were presented with 80 short
      sentences half of which were factually correct, and the other half factually
      incorrect. The diagnosis was made on the basis of repeated neurological
      examinations as well as the standardized assessment using a Coma Recovery Scale
      Revised (CRS-R). fMRI blood oxygen level dependent signal was recorded in an
      event-related design time-locked to the end word of the sentences. In the
      contrast "incorrect-minus-correct" significant activations in the relevant brain
      regions were obtained in 17 (81%) controls and in 16 (29%) patients. Among
      patients, the 16 responders had a significantly longer time since accident than
      the 39 non-responders. Responders and non-responders did not differ in terms of
      the diagnosis (UWS vs. MCS), age, CRS-R score, or the degree of brain atrophy.
      The data concur with the results of several earlier studies on UWS/MCS patients,
      with the difference that the critical stimuli in those studies were semantically
      incongruent or ambiguous propositions rather than factually false ones in the
      present experiment. The hypothesis is discussed that the differential response of
      brain language areas to factually correct and incorrect statements does not
      require conscious perception of the statements. 

PMID- 24025065
TI  - Ethical aspects of vegetative and minimally conscious states.
AB  - The growing diffusion of life support procedures, including cardiopulmonary
      resuscitation (CPR) and advanced cardiac life support (ACLS), allows physicians
      to keep a person alive almost indefinitely when the person&#039;s heart has
      stopped beating autonomously or spontaneous breathing is precluded. However, in
      some cases patients are brought back to life but remain in a vegetative state
      (VS) or in a minimally conscious state (MCS). This prompts reflections on the
      'pros and cons' of life support procedures and on the recommended conduct to be
      adopted for the general management of patients who survive in a VS or MCS.
      Important issues to be debated include the choice of therapeutic management which
      guarantees for the patient the maximum possible physical and mental well-being;
      the distinction between 'worthwhile' and 'disproportionate' treatments; the
      patient&#039;s right to make decisions concerning his or her own health status;
      the possibility to make 'advance directives' when still healthy or when a life
      threatening illness has been diagnosed; the role of relatives and caregivers in
      the choice of the best treatment for unconscious patients and the identification
      of ethically and scientifically valid criteria for the inclusion of unconscious
      patients in studies investigating experimental therapies. 

PMID- 24025066
TI  - Silencing the brain may be better than stimulating it. The GABA effect.
AB  - Cases of recovery from vegetative and minimally conscious state after the
      administration of various pharmacological agents have been recently reported.
      These agents include CNS depressants (zolpidem, baclofen, lamotrigine) and CNS
      stimulants (tricyclic antidepressants, selective serotonin reuptake inhibitors,
      dopaminergic agents, methylphenidate). The action of CNS depressants as awakening
      agents sounds paradoxical, as they are commonly prescribed to slow down brain
      activity in the management of anxiety, muscle tension, pain, insomnia and
      seizures. How these drugs may improve the level of consciousness in some brain
      injured patients is the subject of intense debate. Here we hypothesize that CNS
      depressants may promote consciousness recovery by reversing a condition of GABA
      impairment in the injured brain, restoring the normal ratio between synaptic
      excitation and inhibition, which is the prerequisite for any transition from a
      resting state to goal-oriented activities (GABA impairment hypothesis).
      Alternative or complementary mechanisms underlying the improvement of
      consciousness may include the reversal of a neurodormant state within areas
      affected by diaschisis (diaschisis hypothesis) and the modulation of an
      informative overload to the cortex as a consequence of filter failure in the
      injured brain (informative overload hypothesis). A better understanding of how
      single agents act on neural networks, whose functioning is critical for recovery,
      may help to advance a tailored pharmacological approach in the treatment of
      severely brain injured patients. 

PMID- 24025067
TI  - In-hospital cardiac complications after intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: Data on cardiac complications and their precipitants
      after intracerebral hemorrhage are scarce. We examined the frequency and risk
      factors for serious in-hospital cardiac events in a large cohort of consecutive
      intracerebral hemorrhage patients. METHODS: A retrospective chart review of 1013
      consecutive patients with nontraumatic intracerebral hemorrhage treated at the
      Helsinki University Central Hospital (2005-2010). We excluded patients with
      intraparenchymal hematoma related to sub-arachnoid hemorrhage or intracerebral
      hemorrhage because of fibrinolytic therapies for acute ischemic stroke or
      myocardial infarction. Serious in-hospital cardiac event was defined as any of in
      hospital poststroke acute myocardial infarction, ventricular fibrillation or
      tachycardia, moderate to serious acute heart failure, or cardiac death. RESULTS:
      Among the 948 patients included, >=1 serious in-hospital cardiac event occurred
      in 39 (4.1%) patients after a median delay of two-days from stroke onset (acute
      myocardial infarction in three patients, ventricular fibrillation or tachycardia
      in three patients, acute heart failure in 36 patients, and cardiac death in three
      patients). Hospital stay was longer in patients with serious in-hospital cardiac
      event than in those without (median 12, interquartile range 7-19 vs. 8, 3-14; P =
      0.001), with no difference in in-hospital mortality (23.1% vs. 24.3%; P = 0.86).
      In multivariable logistic regression analysis adjusted for age, gender, and
      diabetes, atrial fibrillation during hospitalization (odds ratio 6.68 for new
      onset atrial fibrillation, 95% confidence interval 2.11-21.18; 4.46 for old
      atrial fibrillation, 2.08-9.56), and history of myocardial infarction (3.20, 1.18
      8.66) were independently associated with serious in-hospital cardiac events.
      CONCLUSIONS: After intracerebral hemorrhage, 4% of patients suffer an acute
      serious cardiac complication. Those with history of myocardial infarction or in
      hospital atrial fibrillation are at greater risk for such events.

PMID- 24025068
TI  - Photodynamic inactivation of clinical isolates of Candida using
      Photodithazine(r).
AB  - This study evaluated the photodynamic inactivation (PDI) mediated by
      Photodithazine((r)) (PDZ) against 15 clinical isolates of Candida albicans,
      Candida glabrata and Candida tropicalis. Each isolate, in planktonic and biofilm
      form, was exposed to PDI by assessing a range of PDZ concentrations and light
      emitting diode fluences. Cell survival of the planktonic suspensions was
      determined by colony forming units (CFU ml(-1)). The antifungal effects of PDI
      against biofilms were evaluated by CFU ml(-1) and metabolic assay. Data were
      analyzed by non-parametric tests (alpha = 0.05). Regardless of the species, PDI
      promoted a significant viability reduction of planktonic yeasts. The highest
      reduction in cell viability of the biofilms was equivalent to 0.9 log10 (CFU ml(
      1)) for C. albicans, while 1.4 and 1.5 log10 reductions were obtained for C.
      tropicalis and C. glabrata, respectively. PDI reduced the metabolic activity of
      biofilms by 62.1, 76.0, and 76.9% for C. albicans, C. tropicalis, and C.
      glabrata, respectively. PDZ-mediated PDI promoted significant reduction in the
      viability of Candida isolates. 

PMID- 24025069
TI  - Design, synthesis, and structure-activity relationships of
      azolylmethylpyrroloquinolines as nonsteroidal aromatase inhibitors.
AB  - A small library of both [2,3-h] and [3,2-f] novel pyrroloquinolines equipped with
      an azolylmethyl group was designed and synthesized as nonsteroidal CYP19
      aromatase inhibitors. The results showed that azolylmethyl derivatives 11, 13,
      14, 21, and 22 exhibited an inhibitory potency on aromatase comparable to that of
      letrozole chosen as a reference compound. When assayed on CYP11B1 (steroid-11beta
      hydroxylase) and CYP17 (17alpha-hydroxy/17,20-lyase), compound 22 was found to be
      the best and most selective CYP19 inhibitor of them all. In a panel of nine human
      cancer cell lines, all compounds were either slightly cytotoxic or not at all.
      Docking simulations were carried out to inspect crucial enzyme/inhibitor
      interactions such as hydrophobic interactions, hydrogen bonding, and heme iron
      coordination. This study, along with the prediction of the pharmacokinetics of
      compounds 11, 13, 14, 21, and 22, demonstrates that the pyrroloquinoline scaffold
      represents a starting point for the development of new pyrroloquinoline-based
      aromatase inhibitors. 

PMID- 24025071
TI  - Development and in vitro evaluation of a buccal drug delivery system based on
      preactivated thiolated pectin.
AB  - The aim of this study was to evaluate the potential of preactivated thiolated
      pectin (Pec-Cys-MNA) for buccal drug delivery. Therefore, a gel formulation
      containing this novel polymer and the model drug lidocaine was prepared and
      investigated in vitro in terms of rheology, mucoadhesion, swelling behavior and
      drug release in comparison to formulations based on pectin (Pec) and thiolated
      pectin (Pec-Cys). Both pectin derivatives showed gel formation without addition
      of any other excipient due to self-crosslinking thiol groups. Under same
      conditions, pectin did not show gel formation. Viscosity of Pec-Cys-based
      formulation increased 92-fold and viscosity of Pec-Cys-MNA-based formulations by
      4958-fold compared to pectin-based formulation. Gels did not dissolve in aqueous
      environment during several hours and were able to take up water. Mucoadhesion of
      pectin on buccal tissue could be improved significantly, value of total work of
      adhesion increased in the following rank order: Pec-Cys-MNA > Pec-Cys > Pec. The
      retention time of a model drug incorporated in gel formulations on buccal mucosa
      under continuous rinsing with phosphate-buffered saline was prolonged, after 1.5
      h 3-fold higher amount of a model drug was to be found on tissue after
      application of Pec-Cys-MNA-based formulation compared to pectin-based and 2-fold
      compared to Pec-Cys-based formulation. The Pec-Cys-MNA-based gel showed a more
      sustained release of lidocaine than Pec-Cys-based gel, whereas pectin solution
      revealed an immediate release. According to these results, the self-crosslinking
      pectin-derivative is a promising tool for buccal application.

PMID- 24025070
TI  - Patients with irritable bowel syndrome are more burdened by co-morbidity and
      worry about serious diseases than healthy controls--eight years follow-up of IBS
      patients in primary care.
AB  - BACKGROUND: Irritable Bowel Syndrome (IBS) is a hidden public health disease that
      affects up to 20% of the general population. Although co-morbidity can affect
      diagnose setting and treatment of the disease, there are few studies concerning
      diagnosed and registered co-morbidity for IBS patients in primary care. The aim
      of this study was to analyse co-morbidity among IBS-patients compared to age- and
      sex-matched controls from the general population using data from a county-wide
      computerized medical record system. METHODS: IBS cases were recruited from three
      Swedish primary health care centres during a five-years period and controls from
      the same corresponding geographical areas. Co-morbidity data for IBS-patients and
      morbidity data for controls were derived from a population-based Health Care
      Register (HCR) covering all diagnoses in primary as well as hospital care in the
      region. Odds Ratios with 95% confidence intervals for morbidity in gastro
      intestinal and non-gastrointestinal diagnoses for cases with irritable bowel
      syndrome compared to controls were calculated separately for each gender and
      diagnosis. RESULTS: We identified more co-morbidity among IBS patients of both
      sexes, compared to matched controls in the general population. Patients with IBS
      were particularly more worried about having a serious disease than their control
      group. The risk among male IBS-cases to get this latter diagnose was three times
      higher compared to the male controls. CONCLUSIONS: In this population based case
      control study, the analysis of diagnoses from the HCR revealed a broad spectrum
      of common co-morbidity and significantly more physician-recorded diagnoses among
      IBS-patients in comparisons to the control group.

PMID- 24025072
TI  - Hydrogel-gauze dressing for moderate-to-severe atopic dermatitis: development and
      efficacy study on atopic dermatitis-like skin lesions in NC/Nga mice.
AB  - Topical emollients are known to provide symptomatic relief for atopic dermatitis.
      In hospitals, wet-wrap therapy has been shown to benefit children with moderate
      to-severe atopic dermatitis (AD), but the application of wet-wraps is tedious and
      time-consuming. Topical emollients have low residence time and often dry out
      easily. The aim of this work was to develop a hydrogel-gauze dressing that is not
      only easy to apply but also rehydrates and traps moisture to provide longer
      relief for AD patients. In this study, a prototype hydrogel-gauze dressing was
      developed with varying ratios of sodium carboxymethylcellulose (NaCMC) and
      propylene glycol. The hydrogel-gauze dressings were assessed based on the
      moisture vapor transmission rate, moisture absorption, mechanical properties and
      storage stability over three months. Then, the efficacy of the hydrogel-gauze
      dressing was compared to topical emollients using transgenic NC/Nga mice with AD
      like lesions. The NaCMC hydrogel-gauze dressings significantly lowered
      transepidermal water loss, and the animals displayed a faster recovery, which
      indicates that hydrogel-gauze dressings can trap moisture more effectively and
      accelerate AD healing. Hence, we propose that hydrogel-gauze dressings can
      potentially become an alternative to wet-wrap therapy due to the ease of
      application and the higher efficacy compared to topical products.

PMID- 24025073
TI  - PBK/TOPK expression in non-small-cell lung cancer: its correlation and prognostic
      significance with Ki67 and p53 expression.
AB  - AIMS: The aim of this study was to evaluate the prevalence of PBK/TOPK (PDZ
      binding kinase/T-LAK cell-originated protein kinase) expression, and explore the
      prognostic significance of PBK/TOPK expression alone and in combination with Ki67
      and p53 expression in non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: We
      detected PBK/TOPK expression in 30 samples of normal lung tissue, 32 lymph node
      metastases and 279 primary non-small-cell lung cancers by immunohistochemistry,
      and analysed the correlation of PBK/TOPK expression with Ki67 and p53 expression
      in primary tumour tissues. The results showed that PBK/TOPK expression was higher
      in lymph node metastases (75%) than in primary tumours (44.8%) and normal lung
      tissues (0%). PBK/TOPK expression was associated with histological type, lymph
      node metastasis, and TNM stage, and was positively correlated with Ki67 and p53
      expression in NSCLC. Univariate and multivariate survival analyses showed that
      PBK/TOPK expression was significantly associated with an unfavourable prognosis
      in NSCLC. The prognosis of patients with tumours positive for both PBK/TOPK
      expression and Ki67 or p53 expression was also significantly unfavourable.
      CONCLUSIONS: PBK/TOPK expression is positively correlated with Ki67 and p53
      expression, and can be used as an independent prognostic factor in NSCLC.

PMID- 24025074
TI  - Preterm delivery risk in women initiating antiretroviral therapy to prevent HIV
      mother-to-child transmission.
AB  - OBJECTIVES: The aim of the study was to describe the relationship between preterm
      delivery (PTD; < 37 weeks of gestation) and antiretroviral therapy in a single
      centre cohort of pregnant women with HIV infection. METHODS: A retrospective
      analysis of data for 331 women who received care in a dedicated HIV antenatal
      clinic between 1996 and 2010 was carried out. Data on first CD4 cell count and
      viral load (HIV-1 RNA copies/mL) recorded in pregnancy, class and timing of
      antiretroviral therapy, gestational age at delivery, and risk factors for and
      causes of PTD were available from a clinical database. RESULTS: Overall, 13.0% of
      deliveries were preterm, of which 53% were severe preterm (< 34 weeks of
      gestation). The lowest rate of PTD was observed in women treated with zidovudine
      monotherapy (6.2%). Higher rates of PTD were observed in women starting
      combination antiretroviral therapy (cART) in pregnancy compared with women
      conceiving while on cART [odds ratio (OR) 2.52; 95% confidence interval (CI) 1.22
      5.20; P = 0.011]. Of the women who were eligible for zidovudine monotherapy on
      the basis of CD4 counts and HIV viral load but who were treated with short-term
      cART to prevent HIV mother-to-child transmission, 28.6% delivered preterm. Women
      on short-term cART remained at the highest risk of PTD compared with zidovudine
      monotherapy in multivariate analysis (OR 5.00; 95% CI 1.49-16.79; P = 0.015).
      CONCLUSIONS: The causes of PTD are multiple and poorly understood. The timing of
      initiation and type of antiretroviral therapy administered during pregnancy
      appear to contribute to PTD risk. Understanding this association should improve
      the safety of antiretroviral therapy in pregnancy without increasing the risk of
      transmission.

PMID- 24025075
TI  - A practical reconstructed phase space approach for ECG arrhythmias
      classification.
AB  - Atrial and ventricular arrhythmias are symptoms of the main common causes of
      rapid death. The severity of these arrhythmias depends on their occurrence either
      within the atria or ventricles. These abnormalities of the heart activity may
      cause an immediate death or cause damage of the heart. In this paper, a new
      algorithm is proposed for the classification of life threatening cardiac
      arrhythmias including atrial fibrillation (AF), ventricular tachycardia (VT) and
      ventricular fibrillation (VF). The proposed technique uses a simple signal
      processing technique for analysing the non-linear dynamics of the ECG signals in
      the time domain. The classification algorithm is based upon the distribution of
      the attractor in the reconstructed phase space (RPS). The behaviour of the ECG
      signal in the reconstructed phase space is used to determine the classification
      features of the whole classifier. It is found that different arrhythmias occupy
      different regions in the reconstructed phase space. Three regions in the RPS are
      found to be more representative of the considered arrhythmias. Therefore, only
      three simple features are extracted to be used as classification parameters. To
      evaluate the performance of the presented classification algorithm, real datasets
      are obtained from the MIT database. A learning dataset is used to design the
      classification algorithm and a testing dataset is used to verify the algorithm.
      The algorithm is designed to guarantee achieving both 100% sensitivity and 100%
      specificity. The classification algorithm is validated by using 45 ECG signals
      spanning the considered life threatening arrhythmias. The obtained results show
      that the classification algorithm attains a sensitivity ranging from 85.7-100%, a
      specificity ranging from 86.7-100% and an overall accuracy of 95.55%.

PMID- 24025076
TI  - Reclassification of captive chimpanzees as endangered would cost lives.
AB  - A reclassification of captive chimpanzees as endangered by the US Fish and
      Wildlife Service (FWS) would have devastating consequences on critical areas of
      basic biomedical research for which chimpanzees are uniquely suitable as animal
      models. It also would have a negative impact on the survival of wild chimpanzees
      and the preservation of the species. 

PMID- 24025077
TI  - The Symposium on Nonhuman Primate Models for AIDS. Introduction.

PMID- 24025078
TI  - Robust suppression of env-SHIV viremia in Macaca nemestrina by 3-drug ART is
      independent of timing of initiation during chronic infection.
AB  - BACKGROUND: Nonhuman primates (NHPs) are an important model organism for studies
      of HIV pathogenesis and preclinical evaluation of anti-HIV therapies. The
      successful translation of NHP-derived data to clinically relevant anti-HIV
      studies will require better understanding of the viral strains and NHP species
      used and their responses to existing antiretroviral therapies (ART). METHODS:
      Five pigtailed macaques (Macaca nemestrina) were productively infected with the
      SIV/HIV chimeric virus SHIV-1157 ipd3N4 following intravenous challenge. After 8
      or 27 weeks, ART (PMPA, FTC, raltegravir) was initiated. Viral load, T-cell
      counts, and production of SHIV-specific antibodies were monitored throughout the
      course of infection and ART. RESULTS: ART led to a rapid and sustained decrease
      in plasma viral load. Suppression of plasma viremia by ART was independent of the
      timing of initiation during chronic infection. CONCLUSIONS: We present a new NHP
      model of HIV infection on antiretroviral therapy, which should prove applicable
      to multiple clinically relevant anti-HIV approaches.

PMID- 24025080
TI  - Inhibitory effect of hydroxypropyl methylcellulose acetate succinate on drug
      recrystallization from a supersaturated solution assessed using nuclear magnetic
      resonance measurements.
AB  - We examined the inhibitory effect of hydroxypropyl methylcellulose acetate
      succinate (HPMC-AS) on drug recrystallization from a supersaturated solution
      using carbamazepine (CBZ) and phenytoin (PHT) as model drugs. HPMC-AS HF grade
      (HF) inhibited the recrystallization of CBZ more strongly than that by HPMC-AS LF
      grade (LF). 1D-1H NMR measurements showed that the molecular mobility of CBZ was
      clearly suppressed in the HF solution compared to that in the LF solution.
      Interaction between CBZ and HF in a supersaturated solution was directly detected
      using nuclear Overhauser effect spectroscopy (NOESY). The cross-peak intensity
      obtained using NOESY of HF protons with CBZ aromatic protons was greater than
      that with the amide proton, which indicated that CBZ had hydrophobic interactions
      with HF in a supersaturated solution. In contrast, no interaction was observed
      between CBZ and LF in the LF solution. Saturation transfer difference NMR
      measurement was used to determine the interaction sites between CBZ and HF.
      Strong interaction with CBZ was observed with the acetyl substituent of HPMC-AS
      although the interaction with the succinoyl substituent was quite small. The
      acetyl groups played an important role in the hydrophobic interaction between HF
      and CBZ. In addition, HF appeared to be more hydrophobic than LF because of the
      smaller ratio of the succinoyl substituent. This might be responsible for the
      strong hydrophobic interaction between HF and CBZ. The intermolecular
      interactions between CBZ and HPMC-AS shown by using NMR spectroscopy clearly
      explained the strength of inhibition of HPMC-AS on drug recrystallization.

PMID- 24025081
TI  - Neuroprotective effects of perflurocarbon (oxycyte) after contusive spinal cord
      injury.
AB  - Spinal cord injury (SCI) often results in irreversible and permanent neurological
      deficits and long-term disability. Vasospasm, hemorrhage, and loss of
      microvessels create an ischemic environment at the site of contusive or
      compressive SCI and initiate the secondary injury cascades leading to progressive
      tissue damage and severely decreased functional outcome. Although the initial
      mechanical destructive events cannot be reversed, secondary injury damage occurs
      over several hours to weeks, a time frame during which therapeutic intervention
      could be achieved. One essential component of secondary injury cascade is the
      reduction in spinal cord blood flow with resultant decrease in oxygen delivery.
      Our group has recently shown that administration of fluorocarbon (Oxycyte)
      significantly increased parenchymal tissue oxygen levels during the usual
      postinjury hypoxic phase, and fluorocarbon has been shown to be effective in
      stroke and head injury. In the current study, we assessed the beneficial effects
      of Oxycyte after a moderate-to-severe contusion SCI was simulated in adult Long
      Evans hooded rats. Histopathology and immunohistochemical analysis showed that
      the administration of 5 mL/kg of Oxycyte perfluorocarbon (60% emulsion) after SCI
      dramatically reduced destruction of spinal cord anatomy and resulted in a marked
      decrease of lesion area, less cell death, and greater white matter sparing at 7
      and 42 days postinjury. Terminal deoxynucleotidyl transferase dUTP nick end
      labeling staining showed a significant reduced number of apoptotic cells in
      Oxycyte-treated animals, compared to the saline group. Collectively, these
      results demonstrate the potential neuroprotective effect of Oxycyte treatment
      after SCI, and its beneficial effects may be, in part, a result of reducing
      apoptotic cell death and tissue sparing. Further studies to determine the most
      efficacious Oxycyte dose and its mechanisms of protection are warranted.

PMID- 24025082
TI  - Impact of deashing treatment on biochar structural properties and potential
      sorption mechanisms of phenanthrene.
AB  - Knowledge of the mineral effects of biochars on their sorption of hydrophobic
      organic contaminants (HOCs) is limited. Sorption of phenanthrene (PHE) by plant
      residue derived biochars (PLABs) and animal waste-derived biochars (ANIBs)
      obtained at two heating treatment temperatures (HTTs) (450 and 600  degrees C)
      and their corresponding deashed biochars was investigated. The decreased surface
      polarity and increased bulk polarity of biochars after deashing treatment
      indicated that abundant minerals of biochars benefit external exposure of polar
      groups associated organic matter (OM). Organic carbon (OC)-normalized
      distribution coefficients (K(oc)) of PHE by biochars generally increased after
      deashing, likely due to enhancement of favorable and hydrophobic sorption sites
      caused by mineral removal. Positive correlation between PHE log K(oc) by PLABs
      and bulk polarity combined with negative correlation between PHE log K(oc) values
      by ANIBs and surface polarity suggested PLABs and ANIBs have different sorption
      mechanisms, probably attributed to their large variation of ash content because
      minerals influenced OM spatial arrangement within biochars. Results of this work
      could help us better understand the impact of minerals, bulk/surface polarity,
      and sorption domain arrangement of biochars on their HOCs sorption and predict
      the fate of HOCs in soils after biochar application.

PMID- 24025083
TI  - Clinical, endoscopic, and histologic features of eosinophilic inflammation of the
      gastrointestinal tract in pediatric liver transplant patients.
AB  - Immunosuppression during the post-transplantation period has led to dramatic
      outcome improvements in PLTR patients. There have been reports describing the
      development of food allergies and an increased predilection for development of
      EGI in PLTR. We aimed to identify the clinical, endoscopic and histologic
      features of EGI in PLTR patients. In this retrospective case series we analyzed
      medical record of all PLTR who underwent EGD and/or colonoscopy at our
      institution from 2000 to 2006. From 2000 to 2006, 32 PLTR patients underwent
      endoscopic evaluation. Seventeen (53%) of 32 patients were diagnosed with EGI.
      Endoscopic abnormalities were seen in the esophagus, stomach, and small intestine
      in 11 (65%), 11 (65%), and four (24%) patients, respectively. Eosinophilic
      inflammation was seen in the esophagus, stomach, and small intestine in 13 (76%),
      10 (59%), and five (29%) patients, respectively. Nine of 17 patients underwent
      colonoscopy and endoscopic abnormalities were seen in four (44%) patients. Five
      patients (56%) had eosinophilic inflammation. In conclusion, we have
      characterized the clinical, endoscopic, and histologic features of EGI.
      Histologic and endoscopic examination reveals that, when present, EGI is often
      found at multiple segments along the gastrointestinal tract. 

PMID- 24025085
TI  - Dissecting the stereocontrol elements of a catalytic asymmetric
      chlorolactonization: syn addition obviates bridging chloronium.
AB  - We report absolute and relative stereochemistry of addition in enantioselective
      chlorolactonizations of 4-phenyl-4-pentenoic acid and its related t-butyl ester,
      catalyzed by (DHQD)2PHAL. Predominant syn addition of the chlorenium and the
      nucleophile across the olefin is observed. As shown by isotopic labeling, NMR
      spectroscopy, and derivative studies, the two new stereocenters formed by
      addition across the double bond are set independently and influenced by different
      factors. These findings suggest a stepwise process via an intermediate capable of
      lactone closure with either stereochemistry, in contradistinction to the more
      familiar scenario in which anti addition is dictated by a bridging chloronium ion
      intermediate. 

PMID- 24025084
TI  - Short-duration hypothermia after ischemic stroke prevents delayed intracranial
      pressure rise.
AB  - BACKGROUND: Intracranial pressure elevation, peaking three to seven post-stroke
      is well recognized following large strokes. Data following small-moderate stroke
      are limited. Therapeutic hypothermia improves outcome after cardiac arrest, is
      strongly neuroprotective in experimental stroke, and is under clinical trial in
      stroke. Hypothermia lowers elevated intracranial pressure; however, rebound
      intracranial pressure elevation and neurological deterioration may occur during
      rewarming. HYPOTHESES: (1) Intracranial pressure increases 24 h after moderate
      and small strokes. (2) Short-duration hypothermia-rewarming, instituted before
      intracranial pressure elevation, prevents this 24 h intracranial pressure
      elevation. METHODS: Long-Evans rats with two hour middle cerebral artery
      occlusion or outbred Wistar rats with three hour middle cerebral artery occlusion
      had intracranial pressure measured at baseline and 24 h. Wistars were randomized
      to 2.5 h hypothermia (32.5 degrees C) or normothermia, commencing 1 h after
      stroke. RESULTS: In Long-Evans rats (n = 5), intracranial pressure increased from
      10.9 +/- 4.6 mmHg at baseline to 32.4 +/- 11.4 mmHg at 24 h, infarct volume was
      84.3 +/- 15.9 mm(3) . In normothermic Wistars (n = 10), intracranial pressure
      increased from 6.7 +/- 2.3 mmHg to 31.6 +/- 9.3 mmHg, infarct volume was 31.3 +/-
      18.4 mm(3) . In hypothermia-treated Wistars (n = 10), 24 h intracranial pressure
      did not increase (7.0 +/- 2.8 mmHg, P < 0.001 vs. normothermia), and infarct
      volume was smaller (15.4 +/- 11.8 mm(3) , P < 0.05). CONCLUSIONS: We saw major
      intracranial pressure elevation 24 h after stroke in two rat strains, even after
      small strokes. Short-duration hypothermia prevented the intracranial pressure
      rise, an effect sustained for at least 18 h after rewarming. The findings have
      potentially important implications for design of future clinical trials.

PMID- 24025086
TI  - Problems experienced by older people when opening medicine packaging.
AB  - OBJECTIVE: Medicine packages can cause problems in daily practice, especially
      among older people. This study aimed to investigate the prevalence of problems
      experienced by older people when opening medicine packaging and to investigate
      how patients manage these problems. METHODS: A convenience sample of 30 community
      pharmacies participated in this study. They selected a systematic sample of 30
      patients over 65 years old with a recent omeprazole prescription, and a
      questionnaire was administered by telephone for at least 10 patients per
      pharmacy. KEY FINDINGS: A total of 317 patients completed the questionnaire. They
      received their omeprazole in a bottle (n = 179, 56.5%), push-through blister pack
      (n = 102, 32.2%) or peel-off blister pack (n = 36, 11.4%). Some 28.4% of all
      patients experienced one or more problems with opening their omeprazole
      packaging; most problems occurred with peel-off blisters (n = 24, 66.7% of all
      respondents using peel-off blisters), followed by push-through blisters (n = 34,
      33.3%) and finally bottles (n = 32, 17.9%). The risk of experiencing problems
      with peel-off blisters and push-through blisters was higher [relative risk 3.7
      (95% confidence interval 2.5-5.5) and 1.9 (1.2-2.8), respectively] than the risk
      of experiencing problems with opening bottles. Two-thirds of respondents reported
      management strategies for their problems. Most were found for problems opening
      bottles (n = 24, 75%), followed by push-through blisters (n = 24, 70.6%) and peel
      off blisters (n = 14, 58.3%). CONCLUSIONS: One in four patients over 65
      experienced difficulties opening their omeprazole packaging and not all of them
      reported a management strategy for their problems. Manufacturers are advised to
      pay more attention to the user-friendliness of product packaging. In addition, it
      is important that pharmacy staff clearly instruct patients on how to open their
      medicine packaging, or assist them in choosing the most appropriate packaging.

PMID- 24025087
TI  - Phytochemical analysis and anti-inflammatory potential of Hyphaene thebaica L.
      fruit.
AB  - Metabolite profiling and biological activity are reported from organic and
      aqueous extracts of the fruit from the desert palm Hyphaene thebaica. Phenolics
      and oxylipids profiles were determined using UPLC-PDA-TOF (ultra performance
      photodiode array-time of flight) high-resolution mass spectrometry in order to
      obtain the molecular formula and exact mass Under optimized conditions, 17
      compounds were simultaneously identified and quantified including 2 cinnamic acid
      derivatives, 5 flavonoids, 6 fatty acids, 2 sphingolipids, a lignan, and a
      stilbene. Sugars composition in the fruit was characterized and quantified by (1)
      H-NMR (nuclear magnetic resonance) with sucrose detected as the major component
      in fruit at a level of 219 mg/g. Fruit organic extracts anti-inflammatory
      potential was assessed in vitro by cyclooxygenase-1 enzyme inhibition. 

PMID- 24025088
TI  - Histological spectrum of mycophenolate mofetil-related colitis: association with
      apoptosis.
AB  - AIMS: The main purpose of this study was to define diagnostic histological
      characteristics of mycophenolate mofetil (MMF)-related colitis in association
      with crypt epithelial cell turnover. METHODS AND RESULTS: The examined material
      included 43 colonic biopsies from renal transplant recipients with MMF
      administration and persistent diarrhoea. Thirty-three cases showed MMF-related
      colitis, while 10 showed no significant changes. The histological findings were
      scored and correlated with the apoptotic index (AI) and with the proliferation
      rate (PR) of the crypt epithelium examined by TUNEL assay and Ki-67
      immunoexpression. Ten cases of Crohn disease and 10 of ulcerative colitis were
      used as comparative groups. Crypt distortion and loss as well as increased
      apoptosis constituted the main features, their degree and combination leading
      either to an inflammatory bowel disease (IBD)-like (82%) or to a graft-versus
      host disease-like pattern (18%). A high AI was associated more frequently with
      moderate and severe crypt distortion, while the values were significantly higher
      compared with the control groups (P < 0.01). High PR was noted in 18 of 29
      (62.1%) of the cases. CONCLUSIONS: The diagnostic hallmark of MMF-related colitis
      is an IBD-like histological pattern in association with increased epithelial
      apoptosis, while apoptotic cell death seems to be a potential pathogenetic factor
      of mucosa injury.

PMID- 24025089
TI  - Manifestation of charged and strained graphene layers in the Raman response of
      graphite intercalation compounds.
AB  - We present detailed multifrequency resonant Raman measurements of potassium
      graphite intercalation compounds (GICs). From a well-controlled and consecutive
      in situ intercalation and high-temperature deintercalation approach the response
      of each stage up to stage VI is identified. The positions of the G and 2D lines
      as a function of staging depend on the charge transfer from K to the graphite
      layers and on the lattice expansion. Ab initio calculations of the density and
      the electronic band structure demonstrate that most (but not all) of the
      transferred charge remains on the graphene sheets adjacent to the intercalant
      layers. This leads to an electronic decoupling of these "outer" layers from the
      ones sandwiched between carbon layers and consequently to a decoupling of the
      corresponding Raman spectra. Thus, higher stage GICs offer the possibility to
      measure the vibrations of single, double, and multilayer graphene under
      conditions of biaxial strain. This strain can additionally be correlated to the
      in-plane lattice constants of GICs determined by X-ray diffraction. The outcome
      of this study demonstrates that Raman spectroscopy is a very powerful tool to
      identify local internal strain in pristine and weakly charged single and few
      layer graphene and their composites, yielding even absolute lattice constants. 

PMID- 24025090
TI  - Sulfotransferase genes: regulation by nuclear receptors in response to xeno/endo
      biotics.
AB  - Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR),
      members of the nuclear receptor superfamily, are two major xeno-sensing
      transcription factors. They can be activated by a broad range of lipophilic
      xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous
      compounds such as steroid hormones and bile acids can also activate PXR and/or
      CAR. These nuclear receptors regulate genes that encode enzymes and transporters
      that metabolize and excrete both xenobiotics and endobiotics. Sulfotransferases
      (SULTs) are a group of these enzymes and sulfate xenobiotics for detoxification.
      In general, inactivation by sulfation constitutes the mechanism to maintain
      homeostasis of endobiotics. Thus, deciphering the molecular mechanism by which
      PXR and CAR regulate SULT genes is critical for understanding the roles of SULTs
      in the alterations of physiological and pathophysiological processes caused by
      drug treatment or environmental exposures.

PMID- 24025091
TI  - Structure, dynamics and selectivity in the sulfotransferase family.
AB  - Combined structure, function and molecular dynamics studies of human cytosolic
      sulfotransferases (SULT1A1 and 2A1) have revealed that these enzymes contain a ~
      30-residue active-site cap whose structure responds to substrates and mediates
      their interactions. The binding of 3'-phosphoadenosine 5'-phosphosulfate (PAPS)
      gates access to the active site by a remodeling of the cap that constricts the
      pore through which acceptors must pass to enter the active site. While the PAPS
      bound enzyme spends the majority (~ 95%) of its time in the constricted state,
      the pore isomerizes between the open and closed states when the nucleotide (PAPS)
      is bound. The dimensions of the open and closed pores place widely different
      steric constraints on substrate selectivity. Nature appears to have crafted these
      enzymes with two specificity settings - a closed-pore setting that admits a set
      of closely related structures, and an open setting that allows a far wider
      spectrum of acceptor geometries. The specificities of these settings seem well
      matched to the metabolic demands for homeostatic and defensive SULT functions.
      The departure of nucleotide requires that the cap open. This isomerization
      dependent release can explain both the product bursts and substrate inhibition
      seen in many SULTs. Here, the experimental underpinnings of the cap-mechanism are
      reviewed, and the advantages of such a mechanism are considered in the context of
      the cellular and metabolic environment in which these enzymes operate.

PMID- 24025092
TI  - Distinct polyadenylation landscapes of diverse human tissues revealed by a
      modified PA-seq strategy.
AB  - BACKGROUND: Polyadenylation is a key regulatory step in eukaryotic gene
      expression and one of the major contributors of transcriptome diversity. Aberrant
      polyadenylation often associates with expression defects and leads to human
      diseases. RESULTS: To better understand global polyadenylation regulation, we
      have developed a polyadenylation sequencing (PA-seq) approach. By profiling
      polyadenylation events in 13 human tissues, we found that alternative cleavage
      and polyadenylation (APA) is prevalent in both protein-coding and noncoding
      genes. In addition, APA usage, similar to gene expression profiling, exhibits
      tissue-specific signatures and is sufficient for determining tissue origin. A 3'
      untranslated region shortening index (USI) was further developed for genes with
      tandem APA sites. Strikingly, the results showed that different tissues exhibit
      distinct patterns of shortening and/or lengthening of 3' untranslated regions,
      suggesting the intimate involvement of APA in establishing tissue or cell
      identity. CONCLUSIONS: This study provides a comprehensive resource to uncover
      regulated polyadenylation events in human tissues and to characterize the
      underlying regulatory mechanism.

PMID- 24025093
TI  - Molecular and phylogenetic analysis of the porcine kobuvirus VP1 region using
      infected pigs from Sichuan Province, China.
AB  - BACKGROUND: Porcine kobuvirus (PKoV) is a member of the Kobuvirus genus within
      the Picornaviridae family. PKoV is distributed worldwide with high prevalence in
      clinically healthy pigs and those with diarrhea. METHODS: Fecal and intestinal
      samples (n = 163) from pig farms in Sichuan Province, China were obtained to
      determine the presence of PKoV using reverse transcription polymerase chain
      reaction assays. Specific primers were used for the amplification of the gene
      encoding the PKoV VP1 protein sequence. Sequence and phylogenetic analyses were
      conducted to clarify evolutionary relationships with other PKoV strains. RESULTS:
      Approximately 53% (87/163) of pigs tested positive for PKoV. PKoV was widespread
      in asymptomatic pigs and those with diarrhea. A high prevalence of PKoV was
      observed in pigs younger than 4 weeks and in pigs with diarrhea. Phylogenetic
      analysis of 36 PKoV VP1 protein sequences showed that Sichuan PKoV strains formed
      four distinct clusters. Two pigs with diarrhea were found to be co-infected with
      multiple PKoV strains. Sequence and phylogenetic analyses revealed diversity
      within the same host and between different hosts. Significant recombination
      breakpoints were observed between the CHN/SC/31-A1 and CHN/SC/31-A3 strains in
      the VP1 region, which were isolated from the same sample. CONCLUSION: PKoV was
      endemic in Sichuan Province regardless of whether pigs were healthy or suffering
      from diarrhea. Based on our statistical analyses, we suggest that PKoV was the
      likely causative agent of high-mortality diarrhea in China from 2010. For the
      first time, we provide evidence for the co-existence of multiple PKoV strains in
      one pig, and possible recombination events in the VP1 region. Our findings
      provide further insights into the molecular properties of PKoV, along with its
      epidemiology.

PMID- 24025094
TI  - Chronic exposure to emissions from photocopiers in copy shops causes oxidative
      stress and systematic inflammation among photocopier operators in India.
AB  - BACKGROUND: We assessed indoor air quality in photocopier centers and
      investigated whether occupational exposure to emissions from photocopiers is
      associated with decline in lung function or changes in haematological parameters,
      oxidative stress and inflammatory status. METHODS: Indoor air quality was
      monitored in five photocopier centers. Pulmonary function was assessed by
      spirometry in 81 photocopier operators (64 male and 17 female) and 43 healthy
      control (31 male and 12 female) subjects. Hematological status, serum thio
      barbituric acid reactive substances (TBARS), total ferric reducing antioxidant
      capacity (FRAC), leukotriene B4 (LTB4), 8-isoprostane, C reactive protein (CRP),
      interleukin 8 (IL-8), clara cell protein (CC-16), intercellular adhesion molecule
      1 (ICAM-1) and eosinophilic cationic protein (ECP) were analyzed. Relationships
      between cumulative exposure, lung function and inflammatory markers were
      assessed. RESULTS: PM10 and PM2.5 were above the permissible levels in all the
      photocopier centers, whereas the levels of carbon monoxide, nitrogen oxides,
      ozone, sulphur dioxide, lead, arsenic, nickel, ammonia, benzene and
      benzo(a)pyrene were within Indian ambient air quality standards. Lung function
      was similar in the photocopier operators and control subjects. Serum TBARS was
      significantly higher and FRAC was lower among photocopier operators when compared
      to healthy controls. Plasma IL-8, LTB4, ICAM-1 and ECP were significantly higher
      in the photocopier exposed group. CONCLUSIONS: Photocopiers emit high levels of
      particulate matter. Long term exposure to emissions from photocopiers was not
      associated with decreased lung function, but resulted in high oxidative stress
      and systemic inflammation leading to high risk of cardiovascular diseases.

PMID- 24025095
TI  - Prevalence of arterial hypertension among Brazilian adolescents: systematic
      review and meta-analysis.
AB  - BACKGROUND: Cardiovascular diseases are the leading cause of death in the world
      and are responsible for a high number of disability-adjusted life years. Elevated
      blood pressure is an independent, linear and continuous risk factor for
      cardiovascular disease and has also been reported in the young population. Brazil
      is a country of continental dimensions, and is very heterogeneous with respect to
      socioeconomic and cultural aspects. Brazilian studies on the subject of
      hypertension in adolescence are not nationally representative, and this provides
      a rationale for the conduction of a meta-analysis to assess the magnitude of the
      problem in the country. METHODS: Hypertension studies in adolescents published
      from 1990 to September 2010 were searched in six electronic databases. Forest
      plots of the prevalence of hypertension were built for the overall population and
      by gender. Heterogeneity was assessed using I2 statistics. Meta-regression models
      were adjusted in order to identify possible sources of heterogeneity. RESULTS: Of
      3,631 articles initially identified, 17 were considered eligible for systematic
      review. The pooled prevalence of hypertension, estimated through random effects
      models, was 8.12% (95% CI 6.24-10.52) for the total population. Overall,
      prevalence was higher in males, 8.75% (95% CI 5.81-12.96) than females, 6.31%,
      (95% CI 4.41-8.96). Several variables were investigated in the heterogeneity
      analysis: region of the study, sample size, age and method of blood pressure
      measurement. The only variables that partially and inconsistently explained the
      observed heterogeneity (I2 = 95.3%) were the region of the country where the
      study was conducted and sample. CONCLUSIONS: There was a large variation in
      hypertension prevalence and in the methods used for its evaluation throughout
      studies with Brazilian adolescents, indicating the need for standardized
      procedures and validated methods for hypertension measurement. Despite the large
      observed heterogeneity, and the small number of studies in some regions of
      Brazil, the pooled prevalence found in both males and females shows that systemic
      arterial hypertension should be monitored in the population aged 10-20 years and
      that specific measures are required to prevent and control the disease, as well
      as its risk factors. Studies that compare regional heterogeneities may contribute
      to the knowledge of factors associated with increased blood pressure among
      adolescents.

PMID- 24025097
TI  - Personalized medicine in oncology, the potential role of nuclear medicine
      imaging.

PMID- 24025096
TI  - Optimising parameters for the differentiation of SH-SY5Y cells to study cell
      adhesion and cell migration.
AB  - BACKGROUND: Cell migration is a fundamental biological process and has an
      important role in the developing brain by regulating a highly specific pattern of
      connections between nerve cells. Cell migration is required for axonal guidance
      and neurite outgrowth and involves a series of highly co-ordinated and
      overlapping signalling pathways. The non-receptor tyrosine kinase, Focal Adhesion
      Kinase (FAK) has an essential role in development and is the most highly
      expressed kinase in the developing CNS. FAK activity is essential for neuronal
      cell adhesion and migration. RESULTS: The objective of this study was to optimise
      a protocol for the differentiation of the neuroblastoma cell line, SH-SY5Y. We
      determined the optimal extracellular matrix proteins and growth factor
      combinations required for the optimal differentiation of SH-SY5Y cells into
      neuronal-like cells and determined those conditions that induce the expression of
      FAK. It was confirmed that the cells were morphologically and biochemically
      differentiated when compared to undifferentiated cells. This is in direct
      contrast to commonly used differentiation methods that induce morphological
      differentiation but not biochemical differentiation. CONCLUSIONS: We conclude
      that we have optimised a protocol for the differentiation of SH-SY5Y cells that
      results in a cell population that is both morphologically and biochemically
      distinct from undifferentiated SH-SY5Y cells and has a distinct adhesion and
      spreading pattern and display extensive neurite outgrowth. This protocol will
      provide a neuronal model system for studying FAK activity during cell adhesion
      and migration events.

PMID- 24025098
TI  - Imaging requirements for personalized medicine: the oncologists point of view.
AB  - While conventional chemotherapy regimens aim to be cytotoxic against
      proliferating cells, molecular targeted therapies are directed at specific cancer
      associated pathways. To optimize cancer care, an early evaluation of treatment
      response is warranted for any tumor type - and for any treatment - by using
      conventional imaging modalities such as ultrasound, CT and MR, FDG-PET or
      specific radiotracer. FDG-PET is one of the most extensively and successfully
      used imaging modalities to achieve an early response evaluation. A high SUV-value
      is a surrogate for malignancy in terms of cancer care and a decrease in FDG
      uptake after therapy is associated with treatment response and a favorable
      clinical outcome. Anyhow, the potential of PET reaches further. By providing
      metabolic information PET (with or without CT) can help to select patients for
      targeted therapy and to adapt treatment protocols. PET with FDG and maybe other,
      more specific PET tracers, promises to direct in a better way personalized cancer
      care and thus promote translational research. An interesting aspect of molecular
      imaging is the ability to achieve knowledge on distribution and expression levels
      of a given receptor. Hereby, imaging could help in guiding systemic treatment
      given a broad spectrum of radiotracers, detecting specific mutations at molecular
      level in vivo. From an oncologists point of view the concept of 'personalized
      medicine' should evolve to include 'personalized imaging' as well as
      'personalized treatment' in order to optimize cancer care, reduce side effects
      and improve quality of life for cancer patients. 

PMID- 24025099
TI  - Radiolabeled probes targeting tyrosine-kinase receptors for personalized
      medicine.
AB  - Receptor tyrosine kinases (RTK) are transmembrane receptors regulating cellular
      proliferation, differentiation, apoptosis, motility and recruitment of the
      vasculature. Aberrant expression and/or function of RTK have been detected in
      many malignant tumors and are considered to be a part of the transformed
      phenotype. The action of several classes of anti-cancer drugs is based on
      specific recognition of RTK. Monoclonal antibodies target extracellular binding
      domains, while tyrosine kinase inhibitors (TKI) bind to intracellular kinase
      domains to suppress RTK signaling. The issues regarding the efficient use of RTK
      targeting are the inter- and intra-patient heterogeneity of RTK expression and
      the changes of expression levels during the course of disease and in response to
      therapy. Radionuclide molecular imaging of RTK expression may aid in selecting
      patients who would benefit from RTK-targeting therapy and in identifying non
      responders. Therefore, the therapy would be more personalized. Currently,
      radiolabeled proteins (monoclonal antibodies and their fragments, natural
      peptides ligands to RTK and de novo selected affinity proteins) and TKI and their
      analogues are under development for the visualization of RTK. In this review, we
      discuss the advantages and disadvantages of these approaches.

PMID- 24025100
TI  - Radiolabelled probes targeting infection and inflammation for personalized
      medicine.
AB  - Inflammatory and infectious diseases include many different clinical conditions
      not often well recognised and characterized with conventional radiology and
      biochemical tests. Radiological techniques (TC, MRI, US) show anatomical changes
      that usually occur in chronic stages of the disease leading to a delayed
      diagnosis and therapy. The possibility of Nuclear Medicine imaging to detect
      biological and biochemical changes in the earliest phases of diseases, allow the
      clinician not only to promptly identify the infective or inflammatory focus, but
      also to establish the best therapeutic approach for the patient. The recent
      availability of different monoclonal antibodies and analogues of growth and
      signalling factors offers physicians a wide spectrum of promising
      radiopharmaceuticals as markers for different pathological events. Therefore, NM
      may help in therapy decision making, management and follow-up through the
      evaluation of the expression of these specific molecules, leading to the
      development of personalized therapies. The appeal to Nuclear Medicine imaging is
      becoming, indeed, more and more widespread not only for diagnostic purposes, but
      also for monitoring drug efficacy. Several advances have been observed in this
      field, and they seem to be very promising for a tailored medicine. 

PMID- 24025101
TI  - Radiolabeled imaging probes targeting angiogenesis for personalized medicine.
AB  - Angiogenesis is essential for tumor growth and inhibiting angiogenesis has become
      an important therapeutic strategy in clinical oncology. Nonetheless, the
      mechanisms behind anti-angiogenic therapeutics as well as resistance to these
      drugs remain unclear. With a lack of validated genetic or molecular biomarkers
      for anti-angiogenic responsiveness, novel methods to identify responsive patients
      are required. Non-invasive nuclear imaging would allow the elucidation of the
      basic drug mechanisms as well as resistance routes and aid the personalization of
      anti-angiogenic therapy by enabling target expression quantification prior to and
      during treatment. This review focuses on the development of radiolabeled probes
      to image four key proteins expressed during angiogenesis, namely vascular
      endothelial growth factor and its receptor, integrin alphav beta3, the
      extracellular domain of fibronectin and matrix metalloproteases, and how these
      probes can be utilized for personalized anti-angiogenic therapy.

PMID- 24025102
TI  - Molecular imaging of apoptosis for early prediction of therapy efficiency.
AB  - Evasion of apoptosis is one of the hallmarks of cancer and any effective therapy
      primarily attempts to induce apoptosis. The evaluation of the degree of success
      of cancer therapy is currently mainly based on clinical and laboratory parameters
      and in a later stage on tumor shrinkage. However, none of these parameters
      provide an objective and early analysis of a therapeutic effect. Molecular
      imaging may provide a tool for this purpose by using not only pathophysiological
      but also biochemical effects of the therapy. First in the field, FDG-PET has been
      explored and demonstrated to offer insight in the amount of viable cells, even
      though false positives are commonly due to the lack of specificity of this
      particular radiopharmaceutical. More specific markers target the dying cells
      instead of those remaining alive. Specific apoptosis markers have been developed
      of which the radiolabeled Annexin A5 is the most intensely studied probe. Site
      specific labeling strategies have improved this imaging probe with good results
      both in pre-clinical studies and in clinical trials, with promises for clinical
      applications. Caspase sensitive probes, such as the isatines, can also
      effectively image apoptosis but are limited due to the high background
      activities. More recent discoveries of small apoptosis sensitive probes, such as
      (18)F-ML10, are currently being explored. In this review, the most important
      apoptosis sensitive probes are described from both a pre-clinical and a clinical
      perspective, highlighting their potential but also their limitations as an early
      marker for therapeutic success. It seems that apoptosis imaging can help to guide
      therapy, not by replacing the current methodology but by providing additional and
      useful information. 

PMID- 24025103
TI  - Development of peptide and protein based radiopharmaceuticals.
AB  - Radiolabelled peptides and proteins have recently gained great interest as
      theranostics, due to their numerous and considerable advantages over small
      (organic) molecules. Developmental procedures of these radiolabelled biomolecules
      start with the radiolabelling process, greatly defined by the amino acid
      composition of the molecule and the radionuclide used. Depending on the
      radionuclide selection, radiolabelling starting materials are whether or not
      essential for efficient radiolabelling, resulting in direct or indirect
      radioiodination, radiometal-chelate coupling, indirect radiofluorination or
      (3)H/(14)C-labelling. Before preclinical investigations are performed, quality
      control analyses of the synthesized radiopharmaceutical are recommended to
      eliminate false positive or negative functionality results, e.g. changed receptor
      binding properties due to (radiolabelled) impurities. Therefore, radionuclidic,
      radiochemical and chemical purity are investigated, next to the general peptide
      attributes as described in the European and the United States Pharmacopeia.
      Moreover, in vitro and in vivo stability characteristics of the peptides and
      proteins also need to be explored, seen their strong sensitivity to proteinases
      and peptidases, together with radiolysis and trans-chelation phenomena of the
      radiopharmaceuticals. In vitro biomedical characterization of the radiolabelled
      peptides and proteins is performed by saturation, kinetic and competition binding
      assays, analyzing KD, Bmax, kon, koff and internalization properties, taking into
      account the chemical and metabolic stability and adsorption events inherent to
      peptides and proteins. In vivo biodistribution can be adapted by linker, chelate
      or radionuclide modifications, minimizing normal tissue (e.g. kidney and liver)
      radiation, and resulting in favorable dosimetry analyses. Finally, clinical
      trials are initiated, eventually leading to the marketing of radiolabelled
      peptides and proteins for PET/SPECT-imaging and therapy of different clinical
      diseases.

PMID- 24025104
TI  - Radiolabelled probes targeting tumor hypoxia for personalized medicine.
AB  - Hypoxia is a characteristic feature of many solid tumors which has been described
      in a wide range of tumor types. Its presence impairs the effectiveness of common
      anti-cancer therapies and accordingly, tumor hypoxia has been associated with an
      aggressive tumor phenotype, poor response to radio- and chemotherapy, and worse
      prognosis. In order to predict outcome and identify patients with a worse
      prognosis and/or patients that would benefit from appropriate treatments, in vivo
      measurement of tumor hypoxia is required. Given the difficulties associated with
      invasive methods, a non-invasive method is of major clinical interest. Although
      several candidate molecules have been labeled with PET and SPECT labels, none of
      them is used in daily clinical routine due to a number of difficulties that
      complicate their use. This review aims to give an overview of the most important
      hypoxia tracers, their prognostic significance and how these tracers can play a
      role in tomorrows personalized medicine. 

PMID- 24025105
TI  - Small molecule PET-radiopharmaceuticals.
AB  - This review describes several aspects required for the development of small
      molecule PET-tracers. Design and selection criteria are important to consider
      before starting to develop novel PET-tracers. Principles and latest trends in
      (11)C and (18)F-radiochemistry are summarized. In addition an update of some new
      developments in regulatory aspects is supplied. 

PMID- 24025106
TI  - Radiolabeled probes targeting G-protein-coupled receptors for personalized
      medicine.
AB  - The G-protein coupled receptor system is involved in a range of cell types and
      actions and as such has a universal potential in identifying cell functions. The
      most widely explored system is that of the somatostatin receptors which has been
      exploited for both imaging and therapy. However, even with this fairly simple
      system, variation is seen in the behaviour of cells between patients and within
      different cell population within the patient. Newer work will exploit different
      ligands in a wider range of both tumour types and non-oncological processes such
      as inflammation. 

PMID- 24025107
TI  - Maternal screening for hypothyroidism and thyroiditis using filter paper
      specimens.
AB  - BACKGROUND AND OBJECTIVE: Hypothyroidism and autoimmune thyroiditis are more
      prevalent than previously considered in women during pregnancy and the
      postpartum, and are associated with adverse effects on the mother and her fetus.
      We determined the efficacy and accuracy of screening women for primary
      hypothyroidism and autoimmune thyroiditis by testing TSH and two thyroid
      antibodies (TAb): thyroperoxidase antibodies (TPOAb) and thyroglobulin antibodies
      (TgAb), in eluates of filter paper specimens collected during early pregnancy and
      the postpartum. METHODS: We enrolled 494 first-trimester pregnant women with no
      exclusion criteria into a prospective study to detect primary hypothyroidism and
      autoimmune thyroiditis. Finger stick blood was applied to filter paper, dried in
      room air, eluted, and promptly tested for TSH and TAb. A total of 178 of the
      pregnant women (36%) were tested in the early postpartum. Women with abnormal
      results had confirmatory serum tests. RESULTS: It was found that 91 pregnant
      women (18.4%) and 43 postpartum women (24.2%) had abnormal TSH values (>4.0 mU/L)
      and/or positive TAb; 140 pregnant women (28.3%) had TSH values >2.5 mU/L. All
      subjects with TSH values >4.0 mU/L tested positive for TAb. Eighteen women (3.6%)
      who tested normal during pregnancy tested abnormal in the postpartum.
      CONCLUSIONS: This study confirms that TSH and TPOAb measured in eluates of blood
      spotted filter paper specimens are excellent screening tests to detect primary
      hypothyroidism and autoimmune thyroiditis in pregnant and postpartum women.
      Results are very comparable to serum data in this population published in the
      literature.

PMID- 24025108
TI  - A case-control study of elective hip surgery among HIV-infected patients:
      exposure to systemic glucocorticoids significantly increases the risk.
AB  - OBJECTIVES: This was a cross-sectional study with a nested case-control analysis
      among a cohort of HIV-infected adults aiming to explore the prevalence of and
      risk factors for elective hip surgery (total hip arthroplasty and resurfacing).
      METHODS: Cases were identified from the out-patient database of HIV-infected
      adults attending one tertiary hospital service. For each case, five controls from
      the same database matched by age, gender and ethnicity were identified. From the
      case notes, information about demographic factors, HIV factors and risk factors
      for hip surgery attributable to osteoarthritis or avascular necrosis (body mass
      index, lipids, alcohol, comorbidities and treatment with oral glucocorticoids)
      was extracted. RESULTS: Among the cohort of 1900 HIV-infected out-patients, 13
      cases (12 male) who had undergone hip surgery [0.7%; 95% confidence interval (CI)
      0.3-1.1%] were identified, with a median age of 47 years. Eleven of the 13 cases
      (85%) were Caucasian and seven of the 13 were in stage 3 of HIV infection. Fewer
      of the cases were in the asymptomatic stage of infection compared with controls
      [odds ratio (OR) for stage 2 or 3 infection 4.0; 95% CI 0.8-18.5]. Ever having
      used oral glucocorticoids was highly significantly associated with elective hip
      surgery (OR 44.6; 95% CI 5.7-347.7). CONCLUSIONS: Among this young cohort, the
      prevalence of elective hip surgery was 0.7%, with the median age at surgery being
      47 years. Ever having been exposed to systemic glucocorticoids was highly
      significantly associated with elective hip surgery, suggesting that the principal
      mechanism underlying the need for surgery was avascular necrosis. There may be an
      increased need for elective hip surgery associated with HIV infection.

PMID- 24025109
TI  - Effect of bismuth oxide on white mineral trioxide aggregate: chemical
      characterization and physical properties.
AB  - AIM: To assess the effect of bismuth oxide (Bi2 O3 ) on the chemical
      characterization and physical properties of White mineral trioxide aggregate
      (MTA) Angelus. METHODOLOGY: Commercially available White MTA Angelus and White
      MTA Angelus without Bi2 O3 provided by the manufacturer especially for this study
      were subjected to the following tests: Rietveld X-ray diffraction analysis (XRD),
      energy-dispersive X-ray analysis (EDX), scanning electron microscopy (SEM),
      compressive strength, Vickers microhardness test and setting time. Chemical
      analysis data were reported descriptively, and physical properties were expressed
      as means and standard deviations. Data were analysed using Student's t-test and
      Mann-Whitney U test (P = 0.05). RESULTS: Calcium silicate peaks were reduced in
      the diffractograms of both hydrated materials. Bismuth particles were found on
      the surface of White MTA Angelus, and a greater amount of particles characterized
      as calcium hydroxide was observed by visual examination on White MTA without Bi2
      O3 . The material without Bi2 O3 had the shortest final setting time (38.33 min,
      P = 0.002), the highest Vickers microhardness mean value (72.35 MPa, P = 0.000)
      and similar compressive strength results (P = 0.329) when compared with the
      commercially available White MTA Angelus containing Bi2 O3 . CONCLUSION: The lack
      of Bi2 O3 was associated with an increase in Vickers microhardness, a reduction
      in final setting time, absence of Bi2 O3 peaks in diffractograms, as well as a
      large amount of calcium and a morphology characteristic of calcium hydroxide in
      EDX/SEM analysis.

PMID- 24025111
TI  - Protocol for seizure prophylaxis following intracerebral hemorrhage study
      (SPICH): a randomized, double-blind, placebo-controlled trial of short-term
      sodium valproate prophylaxis in patients with acute spontaneous supratentorial
      intracerebral hemorrhage.
AB  - RATIONALE: Seizures after intracerebral hemorrhage are a common complication and
      may adversely affect neurological outcome. However, studies are inadequate on the
      utility of prophylactic anticonvulsant therapy in patients with hemorrhagic
      stroke, and the results remains controversial. AIMS: This study aims to determine
      if short-duration sodium valproate prevents seizure onset or improves the
      survival and neurological outcome in adults after acute spontaneous
      supratentorial intracerebral hemorrhage. DESIGN: In this randomized, double
      blinded, placebo-controlled trial, 258 patients meeting the inclusion criteria
      will be enrolled in the Department of Neurosurgery, West China Hospital. In
      addition to standard care, patients will be randomly assigned to receive seven
      day prophylaxis of sodium valproate 500 mg daily (alternatively 400 mg daily by
      intravenous infusion in 250 ml 0.9% normal saline) or matching placebo. Patients
      will be followed up at seven-days, 3, 6, and 12 months. STUDY OUTCOMES: The
      primary outcomes are early (<=7 days) and late onset seizures (>7 days).
      Secondary outcomes include midline shift, enlargement of hematoma, death (all
      cause), adverse effects, and functional outcome assessed by Glasgow Outcome Scale
      and modified Rankin Scale. DISCUSSION: Given the lack of evidence for seizure
      prophylaxis in patients with acute supratentorial intracerebral hemorrhage,
      randomized controlled trials are desperately needed. The results from our study
      are believed to directly influence future prophylactic anticonvulsant therapy of
      intracerebral hemorrhage.

PMID- 24025110
TI  - Building a better dynasore: the dyngo compounds potently inhibit dynamin and
      endocytosis.
AB  - Dynamin GTPase activity increases when it oligomerizes either into helices in the
      presence of lipid templates or into rings in the presence of SH3 domain proteins.
      Dynasore is a dynamin inhibitor of moderate potency (IC50 ~ 15 MUM in vitro). We
      show that dynasore binds stoichiometrically to detergents used for in vitro drug
      screening, drastically reducing its potency (IC50 = 479 MUM) and research tool
      utility. We synthesized a focused set of dihydroxyl and trihydroxyl dynasore
      analogs called the DyngoTM compounds, five of which had improved potency, reduced
      detergent binding and reduced cytotoxicity, conferred by changes in the position
      and/or number of hydroxyl substituents. The Dyngo compound 4a was the most potent
      compound, exhibiting a 37-fold improvement in potency over dynasore for liposome
      stimulated helical dynamin activity. In contrast, while dynasore about equally
      inhibited dynamin assembled in its helical or ring states, 4a and 6a exhibited
      >36-fold reduced activity against rings, suggesting that they can discriminate
      between helical or ring oligomerization states. 4a and 6a inhibited dynamin
      dependent endocytosis of transferrin in multiple cell types (IC50 of 5.7 and 5.8
      MUM, respectively), at least sixfold more potently than dynasore, but had no
      effect on dynamin-independent endocytosis of cholera toxin. 4a also reduced
      synaptic vesicle endocytosis and activity-dependent bulk endocytosis in cultured
      neurons and synaptosomes. Overall, 4a and 6a are improved and versatile helical
      dynamin and endocytosis inhibitors in terms of potency, non-specific binding and
      cytotoxicity. The data further suggest that the ring oligomerization state of
      dynamin is not required for clathrin-mediated endocytosis.

PMID- 24025112
TI  - Nitric oxide compounds have different effects profiles on human articular
      chondrocyte metabolism.
AB  - INTRODUCTION: The pathogenesis of osteoarthritis (OA) is characterized by the
      production of high amounts of nitric oxide (NO), as a consequence of up
      regulation of chondrocyte-inducible nitric oxide synthase (iNOS) induced by
      inflammatory cytokines. NO donors represent a powerful tool for studying the role
      of NO in the cartilage in vitro. There is no consensus about NO effects on
      articular cartilage in part because the differences between the NO donors
      available. The aim of this work is to compare the metabolic profile of
      traditional and new generation NO donors to see which one points out the
      osteoarthritic process in the best way. METHODS: Human healthy and OA
      chondrocytes were isolated from patients undergoing joint replacement surgery,
      and primary cultured. Cells were stimulated with NO donors (NOC-12 or SNP). NO
      production was evaluated by the Griess method, and apoptosis was quantified by
      flow cytometry. Mitochondrial function was evaluated by analysing respiratory
      chain enzyme complexes, citrate synthase (CS) activities by enzymatic assay,
      mitochondrial membrane potential (Deltapsim) by JC-1 using flow cytometry, and
      ATP levels were measured by luminescence assays. Glucose transport was measured
      as the uptake of 2-deoxy-[(3)H]glucose (2-[(3)H]DG). Statistical analysis was
      performed using the Mann-Whitney U test. RESULTS: NOC-12 liberates approximately
      ten times more NO2- than SNP, but the level of cell death induced was not as
      profound as that produced by SNP. Normal articular chondrocytes stimulated with
      NOC-12 had reduced activity from complexes I, III y IV, and the mitochondrial
      mass was increased in these cells. Deleterious effects on DeltaPsim and ATP
      levels were more profound with SNP, and this NO donor was able to reduce 2
      [(3)H]DG levels. Both NO donors had opposite effects on lactate release, SNP
      diminished the levels and NOC-12 lead to lactate accumulation. OA chondrocytes
      incorporate significantly more 2-[(3)H]DG than healthy cells. CONCLUSIONS: These
      findings suggest that the new generation donors, specifically NOC-12, mimic the
      OA metabolic process much better than SNP. Previous results using SNP have to be
      considered prudently since most of the effects observed can be induced by the
      interactions of secondary products of NO.

PMID- 24025113
TI  - Chemical treatments for reducing the yellow discoloration of channel catfish
      (Ictalurus punctatus) fillets.
AB  - The effect of chemical pretreatments on the color and carotenoid content of
      yellow discolored channel catfish fillets was studied. The color and carotenoid
      content of the fillets were analyzed by the L*a*b* color system and high
      performance liquid chromatography, respectively. Untreated fillets turned more
      yellow and darker after 12-d storage. Sodium bicarbonate had a beneficial effect
      on reducing the degree of yellowness, but the fillets still turned darker after
      storage. Sodium bisulfite gave the best results with fillets becoming less yellow
      and brighter after storage. Ascorbic acid, butylated hydroxyanisole, citric acid,
      and sodium metabisulfite were not successful at reducing the discoloration. The
      sum of carotenoid contents of untreated fillets decreased significantly (P <
      0.05) during storage as compared to the fresh fillets. However, the sum of the
      carotenoid contents of fillets treated by various chemicals was not significantly
      (P > 0.05) different from the fresh or untreated fillets. The appearance of
      catfish fillets may be improved during storage by pretreating with sodium
      bisulfite. 

PMID- 24025114
TI  - Non-medical use of prescription opioids during the transition to adulthood: a
      multi-cohort national longitudinal study.
AB  - AIMS: To examine non-medical use of prescription opioids (NMUPO) patterns during
      the transition from adolescence to adulthood, and assess individual
      characteristics and other substance use behaviors associated with longitudinal
      patterns of NMUPO. DESIGN: Nationally representative samples of high school
      seniors in the United States (wave 1: modal age 18 years) were followed
      longitudinally across three biennial follow-up waves (waves 2, 3 and 4: modal
      ages 19/20, 21/22 and 23/24 years). SETTING: Data were collected via self
      administered questionnaires to high school seniors and young adults.
      PARTICIPANTS: The longitudinal sample consisted of 27 268 individuals in 30
      cohorts (high school senior years 1976-2005) who participated in all four waves.
      MEASUREMENTS: Self-reports of NMUPO and other substance use behaviors. FINDINGS:
      Approximately 11.6% [95% confidence interval (CI) = 11.2%, 12.0%] of the sample
      reported past-year NMUPO in at least one of the four waves. Among those who
      reported past-year NMUPO in at least one wave, 69.0% (67.6%, 70.4%), 20.5%
      (19.3%, 21.7%), 7.8% (7.1%, 8.6%) and 2.7% (2.3%, 3.1%) reported NMUPO at one,
      two, three and four waves, respectively. Several wave 1 variables were associated
      with greater odds of multiple waves of NMUPO and individuals who reported more
      waves of NMUPO had greater odds of other substance use behaviors. CONCLUSIONS:
      Although most non-medical use of prescription opioids among 18-year-olds in the
      United States appears to be non-continuing, approximately one-third of the sample
      reporting non-medical use of prescription opioids appear to continue use beyond
      age 18 and have elevated odds of other substance use behaviors at ages 23/24.

PMID- 24025116
TI  - Burden, distribution and impact of domestic accidents in a semi-urban area of
      coastal Tamil Nadu, India.
AB  - The objectives of this study are to determine the prevalence of domestic
      accidents, describe the factors associated with domestic accidents and assess the
      medical and economical consequences of domestic accidents. Community-based cross
      sectional study was conducted in a semi-urban area of Tamil Nadu during February
      2013. A total of 3947 study participants were interviewed using a structured
      questionnaire. Study variables included were socio-demography, housing
      conditions, epidemiological factors, medical and economical consequences of
      domestic accidents. Means and proportions were calculated. The prevalence of
      domestic accidents was 12.7%. Out of 500 domestic accidents, falls (54.4%) was
      the most common type of domestic accident. Females and the respondents in age
      group of 21-40 years were more commonly affected. About 60% of victims received
      treatment. Mean duration of hospital stay, mean amount of money spent for
      treatment and mean number of days away from routine work for falls category were
      16 days, US$25 and 8 days, respectively, which are higher than other types of
      accidents. The burden and impact of domestic accidents was high. Therefore, in
      order to prevent and control domestic accidents, promotion of house safety
      measures and creation of awareness among the community using IEC programmes have
      to be undertaken. 

PMID- 24025115
TI  - The saliva microbiome of Pan and Homo.
AB  - BACKGROUND: It is increasingly recognized that the bacteria that live in and on
      the human body (the microbiome) can play an important role in health and disease.
      The composition of the microbiome is potentially influenced by both internal
      factors (such as phylogeny and host physiology) and external factors (such as
      diet and local environment), and interspecific comparisons can aid in
      understanding the importance of these factors. RESULTS: To gain insights into the
      relative importance of these factors on saliva microbiome diversity, we here
      analyze the saliva microbiomes of chimpanzees (Pan troglodytes) and bonobos (Pan
      paniscus) from two sanctuaries in Africa, and from human workers at each
      sanctuary. The saliva microbiomes of the two Pan species are more similar to one
      another, and the saliva microbiomes of the two human groups are more similar to
      one another, than are the saliva microbiomes of human workers and apes from the
      same sanctuary. We also looked for the existence of a core microbiome and find no
      evidence for a taxon-based core saliva microbiome for Homo or Pan. In addition,
      we studied the saliva microbiome from apes from the Leipzig Zoo, and found an
      extraordinary diversity in the zoo ape saliva microbiomes that is not found in
      the saliva microbiomes of the sanctuary animals. CONCLUSIONS: The greater
      similarity of the saliva microbiomes of the two Pan species to one another, and
      of the two human groups to one another, are in accordance with both the
      phylogenetic relationships of the hosts as well as with host physiology.
      Moreover, the results from the zoo animals suggest that novel environments can
      have a large impact on the microbiome, and that microbiome analyses based on
      captive animals should be viewed with caution as they may not reflect the
      microbiome of animals in the wild.

PMID- 24025117
TI  - An atypical case of lymphoproliferative pulmonary involvement in a patient with
      Sjogren's syndrome: a case report.
AB  - BACKGROUND: Sjogren's syndrome is characterized by lymphocytic infiltration of
      the exocrine glands, together with polyclonal B-cell activation, and lung
      diseases are well-known complications of the disease. Therefore, in most cases
      associated with Sjogren's syndrome, infiltrating lymphocytes in the lung specimen
      exhibit the features of B-cells. We herein report an atypical case of
      lymphoproliferative pulmonary involvement in a patient with Sjogren's syndrome.
      CASE PRESENTATION: A 46-year-old female was admitted to our hospital because of
      an abnormal chest roentgenogram finding on a medical checkup. Chest computed
      tomography showed randomly-distributed micronodules and patchy ground-glass
      opacities. A surgical biopsied specimen showed an atypical pattern of
      interstitial pneumonia with numerous lymphoid follicles. Among the infiltrating
      lymphocytes in the lung, only the monoclonality of the T-cells was proven by a
      gene rearrangement analysis, but there was no cytological atypicality or genetic
      disorder revealed by testing the bone marrow aspirate. A diagnosis of Sjogren's
      syndrome was made based on the patient's other symptoms and these negative
      findings. The patient's pulmonary lesions have been successfully treated and
      remission has been maintained for over three years with corticosteroid treatment
      alone. CONCLUSION: The present patient was an atypical case of
      lymphoproliferative pulmonary involvement in a patient with Sjogren's syndrome.
      Although monoclonality of the infiltrating T-cells was proven, the clinical
      course and the findings of the imaging and laboratory examinations were
      inconsistent with the previously-reported cases of primary pulmonary T-cell
      lymphoma. This suggests that the monoclonality of lymphocytes does not always
      define malignancy. The diagnosis of malignant lymphoma or lymphoproliferative
      diseases should be made clinically, pathologically and cytogenetically to rule
      out other similar diseases.

PMID- 24025118
TI  - Indomethacin: new polymorphs of an old drug.
AB  - This study reports the appearance and characterization of multiple new
      polymorphic forms of indomethacin. Considering the interest in amorphous
      suspensions for toxicology studies of poorly water-soluble drugs, we sought to
      investigate the crystallization behavior of amorphous indomethacin in aqueous
      suspension. Specifically, the effect of pH and temperature on crystallization
      behavior was studied. Quench cooled amorphous powder was added to buffered media
      at different pH values (1.2, 4.5, and 6.8) at 5 and 25  degrees C. Both the solid
      and the solution were analyzed at different time points up to 24 h. Attenuated
      total reflection Fourier transform infrared (ATR-FTIR) spectroscopy (with
      principal component analysis) was used to study solid-phase transformations and
      ultraviolet (UV) spectroscopy used to probe solution concentration. The
      crystallization onset time decreased and rate of crystallization increased with
      increasing pH and temperature. Diverse polymorphic forms were observed, with
      three new forms being identified; these were named epsilon, zeta, and eta. At 25 
      degrees C, the amorphous form recrystallized directly to the alpha form, except
      at pH 6.8, where it initially converted briefly into the epsilon form. At 5 
      degrees C, all three new polymorphic forms were observed sequentially in the
      order epsilon, zeta, and then eta, with the number of these forms observed
      increasing sequentially with decreasing pH. The three new forms exhibited
      distinct X-ray powder diffraction (XPRD), differential scanning calorimetry
      (DSC), and FTIR and Raman spectroscopy profiles. The solution concentration
      profiles suggest that the relative physical stabilities of the polymorphs at 5 
      degrees C from lowest to highest is epsilon < zeta < eta < alpha. The appearance
      of new polymorphs in this study suggests that amorphous suspensions are worth
      considering when performing polymorphic screening studies. 

PMID- 24025119
TI  - Examining the spatial congruence between data obtained with a novel activity
      location questionnaire, continuous GPS tracking, and prompted recall surveys.
AB  - BACKGROUND: Place and health researchers are increasingly interested in
      integrating individuals' mobility and the experience they have with multiple
      settings in their studies. In practice, however, few tools exist which allow for
      rapid and accurate gathering of detailed information on the geographic location
      of places where people regularly undertake activities. We describe the
      development and validation of a new activity location questionnaire which can be
      useful in accounting for multiple environmental influences in large population
      health investigations. METHODS: To develop the questionnaire, we relied on a
      literature review of similar data collection tools and on results of a pilot
      study wherein we explored content validity, test-retest reliability, and face
      validity. To estimate convergent validity, we used data from a study of users of
      a public bicycle share program conducted in Montreal, Canada in 2011. We examined
      the spatial congruence between questionnaire data and data from three other
      sources: 1) one-week GPS tracks; 2) activity locations extracted from the GPS
      tracks; and 3) a prompted recall survey of locations visited during the day.
      Proximity and convex hull measures were used to compare questionnaire-derived
      data and GPS and prompted recall survey data. RESULTS: In the sample, 75% of
      questionnaire-reported activity locations were located within 400 meters of an
      activity location recorded on the GPS track or through the prompted recall
      survey. Results from convex hull analyses suggested questionnaire activity
      locations were more concentrated in space than GPS or prompted-recall locations.
      CONCLUSIONS: The new questionnaire has high convergent validity and can be used
      to accurately collect data on regular activity spaces in terms of locations
      regularly visited. The methods, measures, and findings presented provide new
      material to further study mobility in place and health research.

PMID- 24025120
TI  - Patterns in mortality among people with severe mental disorders across birth
      cohorts: a register-based study of Denmark and Finland in 1982-2006.
AB  - BACKGROUND: Mortality among patients with mental disorders is higher than in
      general population. By using national longitudinal registers, we studied
      mortality changes and excess mortality across birth cohorts among people with
      severe mental disorders in Denmark and Finland. METHODS: A cohort of all patients
      admitted with a psychiatric disorder in 1982-2006 was followed until death or 31
      December 2006. Total mortality rates were calculated for five-year birth cohorts
      from 1918-1922 until 1983-1987 for people with mental disorder and compared to
      the mortality rates among the general population. RESULTS: Mortality among
      patients with severe mental disorders declined, but patients with mental
      disorders had a higher mortality than general population in all birth cohorts in
      both countries. We observed two exceptions to the declining mortality
      differences. First, the excess mortality stagnated among Finnish men born in 1963
      1987, and remained five to six times higher than at ages 15-24 years in general.
      Second, the excess mortality stagnated for Danish and Finnish women born in 1933
      1957, and remained six-fold in Denmark and Finland at ages 45-49 years and seven
      fold in Denmark at ages 40-44 years compared to general population. CONCLUSIONS:
      The mortality gap between people with severe mental disorders and the general
      population decreased, but there was no improvement for young Finnish men with
      mental disorders. The Finnish recession in the early 1990s may have adversely
      affected mortality of adolescent and young adult men with mental disorders. Among
      women born 1933-1957, the lack of improvement may reflect adverse effects of the
      era of extensive hospitalisation of people with mental disorders in both
      countries.

PMID- 24025121
TI  - Validation and application of cavity-enhanced, near-infrared tunable diode laser
      absorption spectrometry for measurements of methane carbon isotopes at ambient
      concentrations.
AB  - Methane is an effective greenhouse gas but has a short residence time in the
      atmosphere, and therefore, reductions in emissions can alleviate its greenhouse
      gas warming effect within a decadal time frame. Continuous and high temporal
      resolution measurements of methane concentrations and carbon isotopic ratios
      (delta(13)CH4) can inform on mechanisms of formation, provide constraints on
      emissions sources, and guide future mitigation efforts. We describe the
      development, validation, and deployment of a cavity-enhanced, near-infrared
      tunable diode laser absorption spectrometry system capable of quantifying
      delta(13)CH4 at ambient methane concentrations. Laboratory validation and testing
      show that the instrument is capable of operating over a wide dynamic range of
      methane concentration and provides a measurement precision for delta(13)CH4 of
      better than +/- 0.5 0/00 (1sigma) over 1000 s of data averaging at ambient
      methane concentrations. The analyzer is accurate to better than +/- 0.5 0/00, as
      demonstrated by measurements of characterized methane/air samples with minimal
      dependence (<1 0/00) of measured carbon isotope ratio on methane concentration.
      Deployment of the instrument at a marsh over multiple days demonstrated how
      methane fluxes varied by an order of magnitude over 2 day deployment periods, and
      showed a 17 0/00 variability in delta(13)CH4 of the emitted methane during the
      growing season.

PMID- 24025122
TI  - Single-operation deracemization of 3H-indolines and tetrahydroquinolines enabled
      by phase separation.
AB  - The single-operation deracemization of 3H indolines and tetrahydroquinolines is
      described. An asymmetric redox approach was employed, in which a phosphoric acid
      catalyst, oxidant, and reductant are present in the reaction mixture. The
      simultaneous presence of both oxidant and reductant was enabled by phase
      separation and resulted in the isolation of highly enantioenriched starting
      materials in high yields. 

PMID- 24025124
TI  - Cytotoxic diterpenoid pseudodimers from the Korean sponge Phorbas gukhulensis.
AB  - Four new cytotoxic diterpenoid pseudodimers (2-5), along with a previously
      reported one, gukulenin A (1), were isolated from the marine sponge Phorbas
      gukhulensis collected off the coast of Gagu-do, Korea. These novel compounds,
      designated gukulenins C-F (2-5), were determined by extensive spectroscopic
      analyses to be pseudodimers of the gagunins, like gukulenin A. The termini of the
      tropolone-containing side chains in gukulenins C-E (2-4) were found to have
      diverse modifications involving acetamides or taurine, whereas gukulenin F (5)
      was formed from 1 by the ring-opening of a cyclic hemiketal. The relative and
      absolute configurations were assigned by Murata's and modified Snatzke's methods
      using a HETLOC experiment and a CD measurement of a dimolybdenum complex,
      respectively. All of these compounds exhibited significant cytotoxicity against
      the K562 and A549 cell lines. 

PMID- 24025123
TI  - Correlated ligand dynamics in oxyiron picket fence porphyrins: structural and
      Mossbauer investigations.
AB  - Disorder in the position of the dioxygen ligand is a well-known problem in
      dioxygen complexes and, in particular, those of picket fence porphyrin species.
      The dynamics of Fe-O2 rotation and tert-butyl motion in three different picket
      fence porphyrin derivatives has been studied by a combination of multitemperature
      X-ray structural studies and Mossbauer spectroscopy. Structural studies show that
      the motions of the dioxygen ligand also require motions of the protecting pickets
      of the ligand binding pocket. The two motions appear to be correlated, and the
      temperature-dependent change in the O2 occupancies cannot be governed by a simple
      Boltzmann distribution. The three [Fe(TpivPP)(RIm)(O2)] derivatives studied have
      RIm = 1-methyl-, 1-ethyl-, or 2-methylimidazole. In all three species there is a
      preferred orientation of the Fe-O2 moiety with respect to the trans imidazole
      ligand and the population of this orientation increases with decreasing
      temperature. In the 1-MeIm and 1-EtIm species the Fe-O2 unit is approximately
      perpendicular to the imidazole plane, whereas in the 2-MeHIm species the Fe-O2
      unit is approximately parallel. This reflects the low energy required for
      rotation of the Fe-O2 unit and the small energy differences in populating the
      possible pocket quadrants. All dioxygen complexes have a crystallographically
      required 2-fold axis of symmetry that limits the accuracy of the determined Fe-O2
      geometry. However, the 80 K structure of the 2-MeHIm derivative allowed for
      resolution of the two bonded oxygen atom positions and provided the best
      geometric description for the Fe-O2 unit. The values determined are Fe-O =
      1.811(5) A, Fe-O-O = 118.2(9) degrees , O-O = 1.281(12) A, and an off-axis tilt
      of 6.2 degrees . Demonstration of the off-axis tilt is a first. We present
      detailed temperature-dependent simulations of the Mossbauer spectra that model
      the changing value of the quadrupole splitting and line widths. Residuals to fits
      are poorer at higher temperature. We believe that this is consistent with the
      idea that population of the two conformers is related to the concomitant motions
      of both Fe-O2 rotations and motions of the protecting tert-butyl pickets. 

PMID- 24025125
TI  - The influence of customized abutments and custom metal abutments on the presence
      of the interproximal papilla at implants inserted in single-unit gaps: a 1-year
      prospective clinical study.
AB  - OBJECTIVES: To assess and compare the papilla presence mesially and distally to
      dental implants restored with customized abutments and custom metal abutments in
      the anterior maxilla. MATERIAL AND METHODS: Thirty-eight patients receiving 38
      single-tooth implants, restored with 26 customized abutments and 12 custom metal
      abutments in the anterior maxillary region were enrolled in this study. The cases
      where did not existed contact point were excluded. Presence/absence of the
      interproximal papilla, inter-tooth-implant distance (ITD) and distance from the
      base of the contact point to dental crest bone of adjacent tooth (CPB) were
      accessed. Global P-values were determined for changes in CPB and papilla score
      over time (P < 0.05). RESULTS: Thirty-six patients with 36 implants were
      available for the 12-month follow-up. The abutments and reconstruction survival
      rate was 100% with no fracture or crown loss. A mean mesial CPB of 5.71 +/- 1.54
      mm and distal CPB of 4.01 +/- 1.73 mm were assessed in the customized abutment
      group for an overall mean papilla presence of 1.69 +/- 0.46. A mean mesial CPB of
      5.41 +/- 1.31 mm and distal CPB of 4.77 +/- 1.21 mm were assessed in the control
      group for an overall mean papilla presence of 1.08 +/- 0.65. CONCLUSIONS: The
      restoration of single-implants using computer-assisted design/computer-assisted
      manufacturing abutments appears to help maintaining a regular papillary filling
      although the variations of the implant positioning or the restoration/teeth
      relation.

PMID- 24025126
TI  - Postmortem examination in the morbidly obese.
AB  - AIMS: The incidence of obesity is rising, and morbid obesity is associated with
      increased mortality rates. Pathologists will therefore encounter increasing
      numbers of postmortems in the morbidly obese. It is essential that pathologists
      recognize morbid obesity and can identify its consequences at postmortem. The
      aims of this study were to assess how often obesity is included in the cause of
      death of morbidly obese individuals, and whether obesity-related causes of death
      are being missed. METHODS AND RESULTS: The postmortem database of the John
      Radcliffe Hospital was searched to identify all medicolegal postmortems performed
      on morbidly obese individuals between January 2007 and September 2012. Of 4742
      coronial postmortems performed, 3911 (82%) reports contained a record of height
      and weight, allowing body mass index calculation. Two hundred and two (5.2%) were
      performed on morbidly obese individuals. Death resulted from natural causes in
      189 (93.6%), of which obesity was included in the medical certificate of cause of
      death in 41 (22%). CONCLUSIONS: Postmortems in the morbidly obese represent a
      significant percentage of the total performed, but recognition of the
      contribution of obesity to death and of obesity-associated conditions is poor.
      Postmortems performed on the morbidly obese represent a distinct group with
      specific causes of death, and should be approached as such.

PMID- 24025127
TI  - Rapid large-area multiphoton microscopy for characterization of graphene.
AB  - Single- and few-layer graphene was studied with simultaneous third-harmonic and
      multiphoton-absorption-excited fluorescence microscopy using a compact 1.55 MUm
      mode-locked fiber laser source. Strong third-harmonic generation (THG) and
      multiphoton-absorption-excited fluorescence (MAEF) signals were observed with
      high contrast over the signal from the substrate. High contrast was also achieved
      between single- and bilayer graphene. The measurement is straightforward and very
      fast compared to typical Raman mapping, which is the conventional method for
      characterization of graphene. Multiphoton microscopy is also proved to be an
      extremely efficient method for detecting certain structural features in few-layer
      graphene. The accuracy and speed of multiphoton microscopy make it a very
      promising characterization technique for fundamental research as well as large
      scale fabrication of graphene. To our knowledge, this is the first time
      simultaneous THG and MAEF microscopy has been utilized in the characterization of
      graphene. This is also the first THG microscopy study on graphene using the
      excitation wavelength of 1.55 MUm, which is significant in telecommunications and
      signal processing. 

PMID- 24025128
TI  - Molecular prevalence of Trypanosoma spp. in wild rodents of Southeast Asia:
      influence of human settlement habitat.
AB  - SUMMARY: This study investigated the molecular prevalence of Trypanosoma lewisi
      and T. evansi in wild rodents from Cambodia, Lao PDR and Thailand. Between 2008
      and 2012, rodents (and shrews) were trapped in nine locations and 616 of these
      were tested using three sets of primers: TRYP1 (amplifying ITS1 of ribosomal DNA
      of all trypanosomes), TBR (amplifying satellite genomic DNA of Trypanozoon
      parasites) and LEW1 (amplifying ITS1 of ribosomal DNA of T. lewisi). Based on the
      size of the PCR products using TRYP1, 17% were positive for T. lewisi and 1.0%
      positive for Trypanozoon. Results were confirmed by sequencing PCR products and
      by using more specific primers (LEW1 and TBR). The specificity of TRYP1 primers,
      however, failed as rodent DNA was amplified in some instances, giving unexpected
      product sizes. Using LEW1 primers, 13.3% of the samples were confirmed positive
      for T. lewisi, both by PCR and sequencing. In Thailand, T. lewisi was found in
      Rattus tanezumi, R. exulans and Berylmys; in Lao PDR, in R. tanezumi and R.
      exulans, and in Cambodia in R. tanezumi, R. exulans and R. norvegicus. Using TBR,
      1.3% of the samples tested positive for Trypanozoon by PCR and sequencing; T.
      evansi is the only species of the Trypanozoon subgenus possibly present in wild
      Asian rodents. These results confirmed its presence in rodents from Thailand (R.
      tanezumi), Lao PDR (R. tanezumi, R. nitidus) and Cambodia (R. tanezumi,
      Niviventer fulvescens, Maxomys surifer). Based on the information related to
      rodent trapping, it was found that rodent species trapped in and around human
      dwellings had a higher prevalence of T. lewisi infection. R. tanezumi and R.
      exulans, two synanthropic species, were mainly found infected in this habitat
      suggesting a role as a reservoir and thus a potential source of T. lewisi for
      human infection.

PMID- 24025130
TI  - Transdermal delivery: product and patent update.
AB  - Transdermal drug delivery is an attractive alternative to the oral and parenteral
      drug delivery. Drugs which are prone to first-pass metabolism can be delivered
      easily in small doses with sustained blood levels through this method. An update
      to available products along with a review of clinical trials and patents are
      discussed in this study. In this review, we have compiled 16 drugs, i.e.
      Buprenorphine, Clonidine, Estradiol, Fentanyl, Granisetron, Lidocaine,
      Methylphenidate, Nicotine, Nitroglycerin, Oxybutynin, Rivastigmine, Rotigotine,
      Scopolamine, Selegiline, Testosterone, Influenza virus vaccine (Microneedle) and
      covering about 22 marketed products on the transdermal system. We present
      instrumental information on them along with the compilation of current clinical
      trials on transdermal systems. We summarize the contents of patents granted in
      last 5 years under different pharmacological categories. This article serves,
      accordingly as a source of available information focused on transdermal drug
      delivery research. 

PMID- 24025131
TI  - 7-Hydroxyquinoline-8-carbaldehydes. 1. Ground- and excited-state long-range
      prototropic tautomerization.
AB  - Ground- and excited-state long-range prototropic tautomerization were studied for
      a series of 7-hydroxyquinoline-8-carbaldehydes (7-HQCs) by (1)H and (13)C NMR
      spectroscopy, photostationary and time-resolved UV-vis spectroscopic methods, and
      quantum chemical computations. These molecules represent trifunctional proton
      donating/accepting systems that have been proposed to serve as models of a
      reversible optically driven molecular switch composed of two moieties: a
      molecular "frame" (7-hydroquinolines, 7-HQs) and a proton "crane" (carbaldehyde
      group). The NMR and electronic absorption spectra indicate a solvent-dependent
      equilibrium between two tautomeric forms, OH (7-quinolinol)) and NH (7(1H)
      quinolinone), already in the ground state of all the compounds under study (7
      hydroxy-2-methoxy-4-methylquinoline-8-carbaldehyde, HMMQC, shows only a trace of
      the NH form in highly polar and/or protic media). Electronic absorption and
      fluorescence of 7-HQCs are rationalized in terms of the ground- and excited-state
      hydrogen atom transfer (HAT). This process was identified by comparing the UV-vis
      spectroscopic properties of 7-HQCs with those of 7-HQs, synthetic precursors of
      the former, as well as with the characteristics of corresponding protonated
      cations and deprotonated anions (part 2). The experimental results are
      corroborated by the density functional theory (DFT) and ab initio computations,
      which shed some light on the differences in photophysics between variously
      substituted 7-HQCs. 

PMID- 24025129
TI  - Delayed seroconversion to STLV-1 infection is associated with mutations in the
      pol and rex genes.
AB  - BACKGROUND: Simian T-cell lymphoma/leukemia virus-1 (STLV-1) infection of non
      human primates can serve as a model for human T-cell lymphoma/leukemia virus
      infection. METHODS: Two tantalus and 2 patas monkeys were transfused with
      intraspecies whole blood infected with STLV-1. Infection was determined by ELISA,
      western blot and DNA PCR analyses. The entire genome of the STLV-1 Tan 90 strain
      and some of the STVL-1 Pat74 strain were amplified using over-lapping primer
      pairs and subsequently sequenced. RESULTS: Followup studies conducted over 2
      years indicated that all 4 monkeys remained healthy despite being infected with
      STLV-1, as determined by PCR, cloning and sequencing analyses. ELISA and Western
      blot analyses indicated that both patas monkeys seroconverted within 2 months of
      transfusion, while one tantalus monkey required one year to seroconvert and the
      other never fully seroconverted. The tantalus monkey which never fully
      seroconverted, failed to react to HTLV-1 p24 Gag antigen. Sequence analyses
      indicated that, while unique, the deduced p24 Gag amino acid sequence of the STLV
      1 Tan 90 strain used for infection was still highly homologous to the HTLV-1 p24
      Gag amino acids present in the ELISA and WB assays. However, a mutation in the
      pol sequence of STLV-1 Tan 90 encoded a putative stop codon, while a common
      deletion in the pol/rex regulatory gene causes significant changes in the Pol,
      and p27 Rex proteins. These same mutations were also observed in the viral DNA of
      both recipient infected tantalus monkeys and were not present in the STLV-1 Pat
      74 strain. CONCLUSION: Our data suggest that seroconversion to STLV-1 infection
      may be prolonged due to the above mutations, and that compensatory molecular
      events must have occurred to allow for virus transmission.

PMID- 24025132
TI  - [Quantifiable changes in HBeAg expression predict therapeutic efficacy of peg
      interferon alfa-2a in patients with HBeAg-positive chronic hepatitis B].
AB  - OBJECTIVE: To investigate whether quantifiable changes in serum levels of
      hepatitis B e antigen (HBeAg) in response to 24 weeks of pegylated-interferon
      alfa-2a (Peg-IFN-a 2a) treatment are predictive of therapeutic efficacy at 48
      weeks of treatment in HBeAg-positive chronic hepatitis B (CHB) patients and to
      investigate the efficacy of using an individualized antiviral treatment strategy.
      METHODS: Ninety-six HBeAg-positive CHB patients with detectable HBeAg at week 24
      of Peg-IFN-a 2a treatment were categorized according to the quantitative change
      in HBeAg (vs. pre-treatment baseline): group A, HBeAg decline more than 2 log;
      group B, HBeAg decline between 1 - 2 log; group C, HBeAg decline less than 1 log,
      which was then randomly divided into two sub-groups: C1 and C2. Group A, B, and
      C1 patients continued the original therapy for an additional 24 weeks, while
      group C2 patients were supplemented with lamivudine (3TC + Peg-IFN-a 2a) for the
      additional 24 weeks of treatment. All patients underwent liver biopsy at the end
      of treatment (week 48), and HBV covalently-closed circular (ccc)DNA was
      quantified as a measure of therapeutic efficacy. A, B, and C1 between-group
      multiple comparisons were made by the Nemenyi test; C1 and C2 between-group
      comparison was made by the Mann-Whitney U test. The significance of between-group
      differences in decreased HBV cccDNA vs. HBeAg/anti-HBe seroconversion was made by
      the Chi-squared test. RESULTS: At week 48, the mean decrease of serum HBV cccDNA
      in each group was: A, 5.8 log10 copy/ml; B, 3.8 log10 copy/ml; C1, 2.8 log10
      copy/ml; C2, 5.7 log10 copy/ml. Statistically significant differences were
      observed for group A vs. B and C1 (P less than 0.01) and C1 vs. C2 (P less than
      0.01); however, the difference between group B and C1 did not reach statistical
      significance (P = 0.19). The mean decrease of HBeAg in each group was: A, 2.7
      log10 S/CO; B, 1.9 log10 S/CO; C1, 0.9 log10 S/CO; C2, 1.6 log10 S/CO.
      Statistically significant differences were observed for group A vs. B and C1 (P
      less than 0.01) and C1 vs. C2 (P less than 0.01). The rate of patients who
      achieved undetectable HBV DNA in each group was: A, 87.5%; B, 34.5%; C1, 17.4%;
      C2, 85.0%. Statistically significant differences were observed for group A vs. B
      and C1 (P less than 0.01) and C1 vs. C2 (P less than 0.01). The HBeAg
      seroconversion rates were: A, 75.0%; B, 24.1%; C1, 13.0%; C2, 25.0%.
      Statistically significant differences were observed only for group A vs. B and C1
      (P less than 0.01). Finally, group A achieved greater reduction in levels of
      cccDNA in liver tissues than B or C1 (P less than 0.01); however, the differences
      between B and C1 and between C1 and C2 did not reach statistical significance.
      CONCLUSION: CHB patients who showed an HBeAg decline of more than 2 log at week
      24 of Peg-IFN-a 2a treatment had better treatment outcome at week 48 than those
      who showed HBeAg decline less than 2 log at week 24. Augmenting the Peg-IFN-a 2a
      treatment with 3TC can improve the clinical response. A change of quantifiable
      HBeAg at week 24 of Peg-IFN-a 2a treatment may be a useful predictor of
      therapeutic efficacy of a 48-week antiviral regimen.

PMID- 24025133
TI  - [Liver histopathological features influencing HBeAg seroconversion in patients
      with HBeAg-positive chronic hepatitis B responding to Peg-IFN treatment].
AB  - OBJECTIVE: To investigate the therapeutic efficiency of antiviral treatment with
      pegylated-interferon (Peg-IFN) for hepatitis B e antigen (HBeAg)-positive chronic
      hepatitis B (CHB) and to explore whether liver histopathological features or
      other factors influence the HBeAg seroconversion treatment response. METHODS:
      Eighty HBeAg-positive CHB patients with diagnosis confirmed by liver puncture
      were treated with Peg-IFN(2a or 2b)body weight dose, once weekly). At treatment
      week 48, the rate of HBeAg seroconversion was determined and used to analyze the
      influence of liver histopathological features (liver biopsy assessment of:
      inflammation, graded G0 to G4; fibrosis stage, graded S0 to S4), sex, age,
      differential levels (pre-treatment baseline vs. week 48 post-treatment) of serum
      alanine transferase (ALT), and HBV DNA, by binary logistic analysis. RESULTS: At
      week 48, the overall rate of HBeAg seroconversion was 30.0%. The rate of HBeAg
      seroconversion gradually advanced with increased liver inflammation (X2 = 8.435,
      P = 0.015): 9.09% of the 22 patients with G1; 31.58% of the 38 patients with G2;
      47.30% of the 19 patients with G3; the one patient with G4. In contrast, the rate
      of HBeAg seroconversion showed a much weaker association with liver fibrosis (X2
      = 5.917, P = 0.116). Only baseline HBeAg level, and no other baseline index, was
      significantly different between the patients who achieved HBeAg seroconversion
      and those who did not. Liver inflammation and baseline HBeAg level were
      identified as influencing factors of HbeAg seroconversion in response to Peg-IFN
      treatment. CONCLUSION: Peg-IFN therapy induces a higher rate of HBeAg
      seroconversion in HBeAg-positive CHB patients with severe liver inflammation;
      histological analysis of pre-treatment liver biopsies may help to identify
      patients most likely to benefit from the antiviral regimen.

PMID- 24025134
TI  - [Efficacy of combination therapy with pegylated-interferon alfa-2a plus ribavirin
      in autoantibody-positive chronic hepatitis C patients].
AB  - To evaluate the therapeutic efficacy of antiviral combination therapy with
      pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody
      positive chronic hepatitis C (CHC) and to investigate the impact of the presence
      of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients
      who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180
      mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75
      kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment
      (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody
      (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody
      type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by
      indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and
      36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time
      quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less
      than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as
      HCV RNA load below the lower limit of detection at 24 weeks after EOT.
      Correlation between autoantibodies and treatment-induced reduced HCV RNA load was
      assessed by univariate analysis of variance or chi-squared tests. Autoantibodies
      were detected in 24 patients, which included 14 ANA-positive patients, five SMA
      positive patients, three LKM1-positive patients, one patient with double
      positivity for ANA and SSB, and one patient with double-positivity for ANA and LC
      1. The autoantibody-positive patients and autoantibody-negative patients showed
      similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs.
      82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively
      reduce the HCV RNA load in autoantibody-positive CHC patients; however, the
      presence of autoantibodies may not be an independent predictor of therapy
      outcome. 

PMID- 24025135
TI  - [Construction of a full-genome HCV replicon with self-cleaving double ribozyme
      sequences and characterization in vitro and in vivo].
AB  - OBJECTIVE: To construct a full-genome hepatitis C virus (HCV) replicon that will
      allow for direct initiation of replication and generation of infectious viral
      particles in an in vitro and in vivo cell system. METHODS: Self-cleaving ribozyme
      sequences were added to each side of the HCV cDNA clone JFH1 and the replication
      deficient clone JFH1/GND, then inserted into the pcDNA3.1 vector downstream of
      the CMV promoter. The resultant recombinant plasmids, pcDNA3.1-RZ-JFH1 and
      pcDNA3.1-RZ-JFH1/GND, were tested for activity in vitro and in vivo by
      transiently transfecting into Huh7.5 cells (5 mug/100 mm culture dish) and
      injecting by high-pressure tail vein injection into Kunming mice (10 - 30
      mug/mouse). Quantitative reverse transcription-PCR, immunofluorescence,
      immunohistochemistry, and serological testing were performed to determine the
      replication ability and assess the properties of the recombinant plasmids in the
      two systems. RESULTS: HCV RNA (1 - 3 * 10(6) copies/ml) was detected in the
      supernatant of transfected Huh7.5 cells up to 16 weeks after transfection. In
      addition, the viral particles from the supernatant were able to infect nave
      Huh7.5 cells. However, only transient viremia was achieved upon tail vein
      injection of the plasmid, and no HCV antigen-positive cells were detected by
      immunohistochemistry nor HCV-specific antibodies by serological testing.
      CONCLUSION: The constructed HCV replicon was capable of stable expression in
      cultured cells and of efficiently generating infectious viral particles in the in
      vitro system over a long period. However, the HCV replicon did not show infective
      characteristics in an in vivo mouse system. The full-length HCV replicon may
      represent a useful tool for in vitro study of HCV pathological mechanisms,
      possibly including anti-HCV drug screening.

PMID- 24025136
TI  - [Facial skin lesions in male patients with liver cirrhosis: role of serum sex
      hormones and correlation with impaired liver function].
AB  - OBJECTIVE: To investigate the relationship between serum sex hormone levels,
      liver function, and pathogenic mechanisms related to cutaneous lesions involving
      the facial skin in male patients with liver cirrhosis. METHODS: Fifty male
      cirrhotic patients with facial skin lesions, including spider angiomas,
      angiotelectasis and special type rash, (mean age: 48.1 +/- 12.2 years) were
      randomly selected for study and enrolled as the case group. Thirty cirrhotic male
      patients without facial skin lesions (mean age: 44.5 +/- 11.7 years) were
      enrolled as the control group. Serum levels of luteinizing hormone (LH),
      follicular stimulating hormone (FSH), prolactin (PRL), estradiol (E2),
      progesterone (PRGE), and testosterone (T) were detected and compared between
      cases and controls by the t-test. All patients were sub-categorized according to
      severity of cirrhosis (Child-Pugh classification) and comparisons between cases
      and controls were carried out by single factor analysis of variance. Logistic
      regression modeling was used to evaluate whether the presence of skin lesions is
      related to changes in markers of liver impairment, including alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil),
      serum albumin (Alb), prothrombin time (PT-SEC), creatinine (CREA), platelet count
      (PLT), and alcoholism. RESULTS: In the cases with spider veins, LH level was
      significantly elevated (t = 2.01) and T level was significantly decreased (t = 
      2.20) (both, P less than 0.05 vs. controls). In the cases with telangiectasia,
      the LH level (t = 3.76, E2 (t = 2.08) and E2/T ratio (t = 2.98) were
      significantly elevated and T level was significantly decreased (t = -3.77) (all,
      P less than 0.05 vs. controls). In the cases with special type rash, FSH level
      was significantly elevated (t = 2.03) and T level was significantly decreased (t
      = -2.01) (both, P less than 0.05 vs. controls). In the case group, E2 levels
      decreased as severity of liver damage increased, while in the control group, E2
      levels increased as severity of liver damage increased; however, the difference
      in average E2 values of the two groups did not reach statistical significance (P
      more than 0.05). In both cases and controls, the T levels were decreased as the
      severity of liver damage increased (F = 3.70, P less than 0.05). Multivariate
      logistic regression analysis showed that increased incidence of facial skin
      lesions is associated with alcoholism (odds ratio (OR) = 4.46, 95% confidence
      interval (CI) = 1.45-13.7, P less than 0.05) and elevated serum levels of AST (OR
      = 11.87, 95% CI = 1.24-113.1, P less than 0.05). CONCLUSION: Alcoholism, impaired
      liver function, and perturbed levels of circulating sex hormones are associated
      with cirrhosis-related facial lesions and may play important roles in the
      pathogenesis of cutaneous lesions in patients with cirrhosis.

PMID- 24025137
TI  - [Clinical features of patients with primary biliary cirrhosis and anti-SP100
      autoantibody positivity].
AB  - OBJECTIVE: To evaluate the clinical features of patients with primary biliary
      cirrhosis (PBC) and positive expression of sp100 autoantibody in order to
      generate a clinical screening profile that may help to increase early diagnosis
      and timely initiation of therapy. METHODS: The clinical data of 70 patients who
      were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at
      the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and
      Pancreatic Medicine were retrospectively collected for analysis. The patients
      were divided according to expression of anti-sp100: positive patients, n = 12;
      negative patients, n = 58. The groups were comparatively analyzed for differences
      in clinical, biochemical, immunological, and histopathological parameters.
      Normally distributed data was compared by t-test, and non-normally data was
      compared by rank-sum test. RESULTS: There was no significant difference in age
      among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/-
      14.7 years, P more than 0.05). The sp100-positive group had significantly more
      women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with
      atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not
      reach statistical significance. The sp100-positive group had significantly higher
      levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl
      transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25
      +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total
      patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of
      those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody
      positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive
      patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not
      associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05).
      CONCLUSION: SP100-positive PBC may show a bias towards the female sex, and may be
      characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical
      differences may manifest as the disease progresses, and changes in
      autoantibodies' expression and liver function markers should be carefully
      monitored in follow-up.

PMID- 24025138
TI  - [Differential expression of protease-activated receptor 2 in a bile duct ligation
      induced rat model of liver fibrosis].
AB  - OBJECTIVE: To observe the dynamic change in expression of protease-activated
      receptor 2 (PAR2) during onset and progression of liver fibrosis by using a rat
      model. METHODS: A cholestatic liver fibrosis model was established in Sprague
      Dawley rats (aged 8-9 weeks, body weight 350 - 400 g) by bile duct ligation
      surgery. Rats receiving a sham operation and unoperated rats served as the
      negative and normal control groups, respectively. At baseline (pre-surgery) and
      post-surgery weeks 2, 4, 6, and 8, five rats from each group were sacrificed for
      whole liver resection. The protein and mRNA expressions of PAR2 and collagen
      I/III were detected by western blotting and RT-PCR, respectively. Between-group
      differences were assessed by analysis of variance testing. RESULTS: At post
      surgery week 2, the liver fibrosis group showed higher expression of PAR2 mRNA
      and protein than either control group. The expression levels of PAR2 continued to
      rise over time in the liver fibrosis group (peaking at week 8), and were
      significantly higher than those detected in the control groups (weeks 4-6: P less
      than 0.05; week 8, P less than 0.05). A similar trend was observed for the
      expression of collagen I/III. CONCLUSION: Dynamic expression of PAR2 observed in
      a cholestatic liver fibrosis rat model may indicate a role for this factor in the
      formation of liver fibrosis.

PMID- 24025139
TI  - [Curative effect of a comprehensive interventional treatment modality on
      hepatocellular carcinoma complicated with main branch portal vein tumor
      thrombosis].
AB  - OBJECTIVE: To explore the therapeutic efficacy of a combined treatment modality
      using transcatheter arterial chemoembolization (TACE) and percutaneous ethanol
      injection (PEI) to treat hepatocellular carcinoma (HCC) complicated with main
      branch intraportal vein tumor thrombosis (PVTT). METHODS: Clinical data was
      collected retrospectively for patients diagnosed with and treated for HCC plus
      main branch PVTT at our hospital between January 2007 and January 2010. The total
      study population (n = 51) consisted of 38 males and 13 females, with an average
      of 50.1 years (range: 24-73). Among these patients, 26 had been treated with TACE
      + PEI (group A) and 25 had been treated with TACE alone (group B). Short-term
      changes in PVTT (i.e. disappearance, shrinkage, and/or stability) and tumor (i.e.
      complete response, partial response, and/or stable disease) were assessed by
      using the t-test (continuous variables) or the Chi-squared or Fisher's exact
      tests (categorical variables). Between-group differences in survival time were
      assessed by the Kaplan-Meier analysis and log-rank test. RESULTS: The follow-up
      time ranged from 3-24 months after treatment, and no serious treatment-related
      complications were recorded for any of the patients (0/51). The time of TACE
      treatment was significantly longer for the patients receiving the combination
      therapy (group A: 3.21.4 vs. group B: 2.40.9, t = 2.22, P = 0.032). The patients
      in group A received between 2-8 PEI treatments. The TACE + PEI combined treatment
      showed significantly better therapeutic efficacy for PVTT (group A: 19/26 vs.
      group B: 10/25, X2 = 5.685, P = 0.019). The tumor response was significantly
      better in patients treated with TACE + PEI at post-treatment month 3 (group A:
      20/26 vs. group B: 18/25, X2 = 0.163, P = 0.705) and month 6 (group A: 17/20 vs.
      10/19, X2 = 2.58, P = 0.027). Finally, the average survival time was
      significantly better in patients treated with TACE + PEI (group A: 12.856.02
      months (range: 5-23) vs. group B: 8.653.39 months (range: 4-16), t = 3.051, P =
      0.004). CONCLUSION: TACE + PEI combination therapy for main branch PVTT in HCC
      patients is more efficacious than TACE alone, and is associated with a longer
      survival time.

PMID- 24025140
TI  - [A preliminary study of the inhibitive efficacy of iodized linoleic acid and its
      fluorodeoxyuridine ester in hepatocellular cancer].
AB  - OBJECTIVE: To explore the potential of iodized linoleic acid (ILA) and its 5
      fluoro-deoxyuridine ester (IFU) to inhibit hepatocellular carcinoma (HCC) cells
      in vitro and tumors in vivo. METHODS: ILA and its constituent component IFU were
      chemically synthesized, purified, and confirmed by 1H-NMR. The HCC cell lines,
      QGY-7703 (5-fluorouracil (5-FU) treatment sensitive) and SMMC-7721 (5-FU
      resistant), were treated with ILA, IFU, 5-FU, or traditional lipiodol for 72
      hours. Survival rates of the treated cells were assessed by the methyl thiazolyl
      tetrazolium method, and used to calculate the IC50 and IC90. In addition, thirty
      nude mice were subcutaneously inoculated with SMMC-7721 cells and randomly
      divided two weeks later into four treatment groups (n = 6 each) for intra-tumoral
      injection of ILA, IFU, 5-FU, lipiodol or DMSO (controls). The rate of tumor
      inhibition (RTI) was calculated for each group at week 4 after treatment.
      RESULTS: For the cultured SMMC-7721 cells, the inhibitory concentrations for ILA,
      IFU, and 5-FU were: IC50: 134.38 mumol/L, 17.55 mumol/L, and 7.38 mumol/L; IC90:
      192.88 mumol/L, 97.63 mumol/L, and more than 200 mumol/L. For the cultured QGY
      7703 cells, the inhibitory concentrations for ILA, IFU, and 5-FU were: IC50:
      109.55 mumol/L, 44.79 mumol/L, and 98.06 mumol/L; IC90: all, more than 200
      mumol/L. In both cell types, the IC50 of lipiodol was more than 400 mumol/L.
      Compared with the RTI of the control mice (100%), the RTI of ILA-treated mice was
      31.9% (t = 2.37, P less than 0.05), of IFU-treated mice was 56.9% (t = 4.91, P
      less than 0.01), and of 5-FU-treated mice was 31.0% (t = 2.59, P less than 0.05).
      The RTI of IFU was significantly stronger than that of either ILA or 5-FU (P less
      than 0.05). The lipiodol treatment showed no inhibition effect on tumors (P more
      than 0.05). CONCLUSION: ILA and IFU can effectively inhibit the growth of HCC
      cells in vitro and tumors in vivo. Furthermore, IFU outperforms ILA in inhibiting
      HCC growth.

PMID- 24025141
TI  - [Effects of inhibited IGF-IR expression on proliferation and apoptosis of human
      hepatocellular carcinoma cell lines].
AB  - OBJECTIVE: To investigate the therapeutic value of inhibiting the expression of
      insulin-like growth factor-I receptor (IGF-IR) using picropodophyllin (PPP) by
      studying the effects on proliferative and metastatic potentials of human
      hepatocellular carcinoma (HCC) using an in vitro cultured cell system. METHODS:
      IGF-IR expression in human HCC cell lines (Bel-7404, Bel-7402, HepG2, and Huh-7)
      and human hepatocytes (L02) was assessed at baseline (pre-treatment) and after
      PPP treatment by western blotting. Changes in cell cycle were analyzed by flow
      cytometry and in cell viability by sulforhodamine B staining. Early apoptosis was
      detected by annexin-V/FITC and propidium iodide double-staining assay. Caspase
      3/7 activity was suppressed by z-VAD-FMK and analyzed by homogeneous luminescence
      assay. Effects on cell motility were tested by wound-scratch test. Between-group
      differences were assessed by t-test or one-way analysis of variance. RESULTS: IGF
      IR was markedly up-regulated in all HCC cell lines (vs. non-hepatoma
      hepatocytes). HCC cells with PPP-inhibited IGF-IR showed time-dependent decreases
      in cell motility and viability. After treatment with PPP for 24 hours, the
      proportion of HCC cells in G1 phase was 2.1% +/- 0.4%, in S phase was 11.0% +/-
      0.7%, and in G2/M phase was 87.1% +/- 0.6%, and no healing was observed in the
      wound-scratch assay. The PPP treatment induced cell apoptosis, as evidenced by
      enhanced caspase-3/7 activity; the proportion of annexin-V+/PI- cells was
      significantly higher in the HepG2 cells than in the non-hepatoma hepatocytes
      (16.4% +/- 0.4% vs. 5.8% +/- 0.2%, t = 14.05, P less than 0.01). After z-VAD-FMK
      treatment, the apoptosis rate was significantly higher in the HepG2 cells than in
      the non-hepatoma hepatocytes (11.3% +/- 0.7% vs. 5.8% +/- 0.2%, t = 11.83, P less
      than 0.01). CONCLUSION: IGF-IR is associated with proliferation, cell motility,
      and apoptosis of HCC cells, and may be a promising molecular target for HCC.

PMID- 24025142
TI  - [Expression of corticotropin-releasing hormone receptor type-1 in intrahepatic
      cholestatic placental tissue].
AB  - OBJECTIVE: To explore the expression level of corticotropin-releasing hormone
      receptor type-1 (CRHR-1) in intrahepatic cholestatic placental (ICP) tissue.
      METHODS: Human placental samples were collected from 10 ICP patients and 10
      healthy controls after parturition at 37-40 weeks of gestation. CRHR-1 protein
      and mRNA expression was assessed by western blotting and nested-real-time
      fluorescence quantitative PCR, respectively. Normally distributed data were
      summarized as mean +/- standard deviation, and intergroup comparisons were made
      by two-tailed Student's t-test. Non-normally distributed data were presented as
      median with interquartile range, and intergroup comparisons were made by Wilcoxon
      test. For all statistical analyses, a two-tailed P-value of less than 0.05 was
      considered statistically significant. RESULTS: The CRHR-1 fluorescence intensity
      was lower in ICP tissues (1.55 +/- 0.28) than in placental tissues from healthy
      controls (1.60 +/- 0.37), but the difference did not reach statistical
      significance (t = 0.349, P = 0.732). The CRHR-1 mRNA content was slightly higher
      in the ICP tissues [0.139(0.268)] than in the placental tissues from healthy
      controls [0.031(0.245)], but the difference did not reach statistical
      significance (t = 1.504, P = 0.136). CONCLUSION: CRHR-1 expression is decreased
      in ICP tissues, which may lead to a smaller volume of placental lobular villi
      vessels and restrict the CRH positive feedback loop, ultimately promoting acute
      hypoxic stress and possible harm to the fetus.

PMID- 24025143
TI  - [Ornithine aspartate and naloxone combined therapy for hepatic encephalopathy
      affects cognitive function, prognosis, and neuropeptide levels].
AB  - OBJECTIVE: To investigate the potential effects on cognitive function, prognosis,
      and neuropeptide levels of patients in response to combination therapy with
      ornithine aspartate plus naloxone for hepatic encephalopathy. METHODS: Eighty
      four consecutive patients diagnosed with hepatic encephalopathy were randomly
      divided into two equal groups. The control group (n = 42) received traditional
      medical treatment, and the research group (n = 42) received the traditional
      medical treatment as well as the combination therapy with ornithine aspartate
      plus naloxone. The supplemental treatment was comprised of daily intravenous
      injection of 10-15 g ornithine aspartate in 250 ml of 5% glucose plus intravenous
      drip of 3 mg naloxone in 100 ml of 5% glucose, and was given in 7-day cycles for
      one or two cycles. The cognitive function of patients was assessed by Hasegawa
      Intelligence Scale (HDS) and Mini-Mental State Examination (MMSE) questionnaires.
      The effective rate and time duration from coma to consciousness were recorded.
      Changes in blood ammonia level, markers of liver function, and neuropeptide
      levels were measured by standard biochemical assays. Intergroup differences were
      assessed by the Chi-squared test. RESULTS: The HDS and MMSE scores of the
      research group were significantly higher than those of the control group after
      therapy. The effective rate, time duration from coma to consciousness, blood
      ammonia, the liver function markers alanine aminotransferase, gamma-glutamyl
      transpeptidase and total bilirubin, and the neuropeptides arginine vasopressin
      and beta-endorphin were remarkably improved after treatment in the research
      group, as compared with that in the control group. CONCLUSION: Supplementing the
      traditional treatment for hepatic encephalopathy with ornithine aspartate plus
      naloxone combination therapy provides better therapeutic outcome than traditional
      treatment alone.

PMID- 24025144
TI  - New Delhi metallo-beta-lactamase I: substrate binding and catalytic mechanism.
AB  - Metallo-beta-lactamases can hydrolyze and deactivate lactam-containing
      antibiotics, which is the major mechanism for causing drug resistance in the
      treatment of bacterial infections. This has become a global concern because of
      the lack of clinically approved inhibitors so far. The emergence of New Delhi
      metallo-beta-lactamase I (NDM-1) makes the situation even more serious. In this
      work, first, the structure of NDM-1 in complex with the inhibitor molecule l
      captopril is investigated by both density functional theory (DFT) and hybrid
      quantum mechanical/molecular mechanical (QM/MM) methods, and the theoretical
      results are in good agreement with the X-ray structure. The Michaelis structure
      with an antibiotic compound (ampicillin) bound in the active site is constructed
      from a recent X-ray structure of the NDM-1 enzyme with hydrolyzed ampicillin. It
      is further simulated using a QM/MM molecular dynamics method. One of the
      interesting binding features of ampicillin in the NDM-1 active site is that the
      conserved C3 carboxylate group is not ligated with Zn2 but rather is only
      hydrogen-bonded with N220 and K211. A bridging hydroxide ion is suggested to
      connect two zinc cofactors. This hydroxide ion is also hydrogen-bonded with D124.
      Subsequent reaction path calculations indicate that the initial step of lactam
      ring-opening occurs through a concerted step in which the cleavage of the C-N
      bond and the transfer of the hydrogen bond to D124 are nearly concerted. The
      ligand bond between Zn2 and the C3 carboxylate group forms after the first step
      of nucleophilic addition. The calculated activation energy barrier height is
      about 19.4 kcal/mol for the hydrolysis of ampicillin, which can be compared with
      the experimental value of 15.8 kcal/mol derived from kcat = 15 s(-1). The overall
      mechanism is finally confirmed by a subsequent DFT study of a truncated active
      site model. 

PMID- 24025145
TI  - A genome-wide association study of chemotherapy-induced alopecia in breast cancer
      patients.
AB  - INTRODUCTION: Chemotherapy-induced alopecia is one of the most common adverse
      events caused by conventional cytotoxic chemotherapy, yet there has been very
      little progress in the prevention or treatment of this side effect. Although this
      is not a life-threatening event, alopecia is very psychologically difficult for
      many women to manage. In order to improve the quality of life for these women, it
      is important to elucidate the molecular mechanisms of chemotherapy-induced
      alopecia and develop ways to effectively prevent and/or treat it. To identify the
      genetic risk factors associated with chemotherapy-induced alopecia, we conducted
      a genome-wide association study (GWAS) using DNA samples from breast cancer
      patients who were treated with chemotherapy. METHODS: We performed a case-control
      association study of 303 individuals who developed grade 2 alopecia, and compared
      them with 880 breast cancer patients who did not show hair loss after being
      treated with conventional chemotherapy. In addition, we separately analyzed a
      subset of patients who received specific combination therapies by GWASs and
      applied the weighted genetic risk scoring (wGRS) system to investigate the
      cumulative effects of the associated SNPs. RESULTS: We identified an SNP
      significantly associated with drug-induced grade 2 alopecia (rs3820706 in CACNB4
      (calcium channel voltage-dependent subunit beta 4) on 2q23, P = 8.13 * 10(-9), OR
      = 3.71) and detected several SNPs that showed some suggestive associations by
      subgroup analyses. We also classified patients into four groups on the basis of
      wGRS analysis and found that patients who classified in the highest risk group
      showed 443 times higher risk of antimicrotubule agents-induced alopecia than the
      lowest risk group. CONCLUSIONS: Our study suggests several associated genes and
      should shed some light on the molecular mechanism of alopecia in chemotherapy
      treated breast cancer patients and hopefully will contribute to development of
      interventions that will improve the quality of life (QOL) of cancer patients.

PMID- 24025146
TI  - Seat-belt use still low in Kuwait: self-reported driving behaviours among adult
      drivers.
AB  - Kuwait mandated seat-belt use by drivers in 1976 and by front seat passengers in
      1994. The study objectives were to identify and estimate current factors
      associated with seat-belt use and levels of potentially unsafe driving behaviours
      in Kuwait. In 2010, 741 adults were surveyed regarding driving habits and
      history. Only 41.6% of drivers reported always using a seat belt. Front seat
      passenger belt use was more common (30.5%) than rear seat belt use (6.5%).
      Distracted driving behaviours were common, including mobile phone use ('always'
      or 'almost always': 51.1%) and texting/SMS (32.4%). Logistic regression indicated
      that drivers who were young (18-19 years), male, Kuwaiti nationals or non-Kuwaiti
      Arabs, drove over the speed limit, had traffic violation tickets or >1 car
      crashes in the last year, were less likely to use seat belts. Targeted
      initiatives to increase public awareness and to enforce car-safety legislation,
      including use of seat belts, are necessary to decrease the health burden of car
      crashes in Kuwait.

PMID- 24025147
TI  - Virological response rates for telaprevir-based hepatitis C triple therapy in
      patients with and without HIV coinfection.
AB  - OBJECTIVES: Pegylated-interferon/ribavirin dual therapy for hepatitis C virus
      (HCV) infection has a lower sustained virological response (SVR) rate in HIV/HCV
      coinfected patients than in HCV monoinfected patients, but little is known about
      the relative effectiveness of teleprevir-based triple therapy in the two groups.
      METHODS: Data on 33 coinfected and 116 monoinfected patients were analysed on an
      intention-to-treat basis. SVR12 was defined as undetectable HCV RNA at week 12
      post-end-of-treatment, severe anaemia as haemoglobin <= 89 g/L or a drop of >= 45
      g/L, and advanced fibrosis/cirrhosis as Fib-4 >= 3.25. All coinfected patients
      had well controlled HIV infection. RESULTS: The groups were similar in age,
      gender, percentage with Fib-4 >= 3.25 and HCV viral load, but differed in
      previous treatment response, with more coinfected patients being nonresponders or
      treatment-intolerant (75.8% vs. 50.0% for monoinfected patients; P < 0.01).
      During treatment, the percentages of patients with undetectable HCV RNA were
      similar, but, surprisingly, this percentage tended to be higher in coinfected
      patients. SVR12 rates were 60.6% in coinfected patients vs. 42.2% in monoinfected
      patients (P = 0.06). In multivariable analysis, SVR12 was associated with HIV
      infection [odds ratio (OR) 3.55; P < 0.01], African American race (OR 0.37; P =
      0.03) and previous treatment response (OR 0.46; P = 0.03). Rates of severe
      anaemia (45.5 vs. 58.6% in coinfected and monoinfected patients, respectively; P
      = 0.18) were similar in the two groups, but rash (15.2 vs. 34.5%, respectively; P
      = 0.03) and rectal symptoms (12.1 vs. 43.1%, respectively; P < 0.01) were less
      common in coinfected patients. CONCLUSIONS: Virological responses of coinfected
      and monoinfected patients did not differ significantly, but tended to be higher
      in coinfected patients, who had a 60.6% SVR12 rate. Telaprevir-based triple
      therapy is a promising option for coinfected patients with well-controlled HIV
      infection.

PMID- 24025148
TI  - Monocyte chemotactic protein-1 level in the aqueous humour as a prognostic factor
      for the outcome of trabeculectomy.
AB  - BACKGROUND: The aim of this study was to elucidate the effects of the aqueous
      humour monocyte chemotactic protein-1 level on the surgical outcome of
      trabeculectomy in cases of phakic glaucoma. DESIGN: Retrospective study.
      PARTICIPANTS: Fifty-three cases of open-angle glaucoma. METHODS: At the time of
      trabeculectomy, aqueous humour samples were collected before any incisions were
      made. The monocyte chemotactic protein-1 level was then determined by
      immunoassay. The Cox proportional hazards test was used to analyse the clinical
      factors related to failure of trabeculectomy. Subsequently, the success
      probability was calculated by Kaplan-Meier analysis and cumulative success
      probabilities were analysed by the log-rank test. MAIN OUTCOME MEASURES:
      Probability of success. RESULTS: In 30 phakic glaucoma and 23 pseudophakic
      glaucoma cases, the mean monocyte chemotactic protein-1 levels in aqueous humour
      were 1165.2 and 2152.9 pg/mL, respectively; the difference was statistically
      significant (P < 0.0001). Univariate analysis showed that the outcomes of surgery
      were correlated with the monocyte chemotactic protein-1 level, but not with age,
      gender, diagnosis of exfoliation glaucoma, pseudophakic status or
      pretrabeculectomy intraocular pressure. Subsequent multivariate analysis revealed
      that only the aqueous humour monocyte chemotactic protein-1 level was
      significantly correlated with the outcomes of trabeculectomy (P = 0.043). Among
      the 30 phakic glaucoma eyes, the success probabilities after trabeculectomy were
      significantly different between the high and low monocyte chemotactic protein-1
      groups (P = 0.018). CONCLUSION: In open-angle glaucoma patients, the monocyte
      chemotactic protein-1 level is a prognostic factor for the results of
      trabeculectomy.

PMID- 24025149
TI  - Analysis of the gut microbiota of walking sticks (Phasmatodea).
AB  - BACKGROUND: Little is known about the Phasmatodea gut microbial community,
      including whether phasmids have symbiotic bacteria aiding in their digestion.
      While symbionts are near ubiquitous in herbivorous insects, the Phasmatodea's
      distinctively thin body shape precludes the gut enlargements needed for microbial
      fermentation. High-throughput sequencing was used to characterize the entire
      microbiota of the fat bodies, salivary glands, and anterior and posterior midguts
      of two species of walking stick. RESULTS: Most bacterial sequences belonged to a
      strain of Spiroplasma (Tenericutes) found primarily in the posterior midgut of
      the parthenogenetic species Ramulus artemis (Phasmatidae). Beyond this, no
      significant differences were found between the R. artemis midgut sections or
      between that species and Peruphasma schultei (Pseudophasmatidae). Histological
      analysis further indicated a lack of bacteriocytes. CONCLUSIONS: Phasmids are
      unlikely to depend on bacteria for digestion, suggesting they produce enzymes
      endogenously that most other herbivorous insects obtain from symbionts. This
      conclusion matches predictions based on phasmid anatomy. The role of Spiroplasma
      in insects warrants further study.

PMID- 24025150
TI  - Relative refractoriness of left ventricular contraction underlies human
      tachycardia-induced mechanical and electrical alternans.
AB  - BACKGROUND: Mechanical alternans (MA) and electrical alternans (EA) are
      predictors of cardiac events. Experimental studies have suggested that
      refractoriness of calcium cycling underlies these cardiac alternans. However,
      refractoriness of left ventricular contraction has not been examined in patients
      with cardiac alternans. METHODS: In 51 patients with miscellaneous heart
      diseases, incremental right atrial pacing was performed to induce MA and EA. MA
      was quantified by alternans amplitude (AA: the difference between left
      ventricular dP/dt of a strong beat and that of a weak beat), and AA at 100/min
      (AA100) and maximal AA (AAmax) were measured. EA was defined as alternation of T
      wave morphology in 12-lead electrocardiogram. Relative refractoriness of left
      ventricular contraction was examined by drawing the mechanical restitution curve
      under a basal coupling interval (BCL) of 600 ms (100/min) and was assessed by the
      slope at BCL (Deltamechanical restitution). Postextrasystolic potentiation (PESP)
      was also examined and the slope of PESP curve (DeltaPESP) was assessed as a
      property to alternate strong and weak beats. RESULTS: MA and EA were induced in
      19 patients and in none at 100/min or less, and at any heart rate in 32 and in
      10, respectively. AA100 and AAmax correlated positively with Deltamechanical
      restitution and negatively with DeltaPESP. Patients with EA had a significantly
      larger Deltamechanical restitution and a significantly larger absolute value of
      DeltaPESP than those without. CONCLUSIONS: In patients with MA and EA, the left
      ventricular contractile force during tachycardia is under relative refractoriness
      and prone to cause large fluctuation of contractile force.

PMID- 24025151
TI  - Detection and quantification of a mycorrhization helper bacterium and a
      mycorrhizal fungus in plant-soil microcosms at different levels of complexity.
AB  - BACKGROUND: Host plant roots, mycorrhizal mycelium and microbes are important and
      potentially interacting factors shaping the performance of mycorrhization helper
      bacteria (MHB). We investigated the impact of a soil microbial community on the
      interaction between the extraradical mycelium of the ectomycorrhizal fungus
      Piloderma croceum and the MHB Streptomyces sp. AcH 505 in both the presence and
      the absence of pedunculate oak microcuttings. RESULTS: Specific primers were
      designed to target the internal transcribed spacer of the rDNA and an intergenic
      region between two protein encoding genes of P. croceum and the intergenic region
      between the gyrA and gyrB genes of AcH 505. These primers were used to perform
      real-time PCR with DNA extracted from soil samples. With a sensitivity of 10
      genome copies and a linear range of 6 orders of magnitude, these real-time PCR
      assays enabled the quantification of purified DNA from P. croceum and AcH 505,
      respectively. In soil microcosms, the fungal PCR signal was not affected by AcH
      505 in the absence of the host plant. However, the fungal signal became weaker in
      the presence of the plant. This decrease was only observed in microbial filtrate
      amended microcosms. In contrast, the PCR signal of AcH 505 increased in the
      presence of P. croceum. The increase was not significant in sterile microcosms
      that contained plant roots. CONCLUSIONS: Real-time quantitative PCR assays
      provide a method for directly detecting and quantifying MHB and mycorrhizal fungi
      in plant microcosms. Our study indicates that the presence of microorganisms and
      plant roots can both affect the nature of MHB-fungus interactions, and that
      mycorrhizal fungi may enhance MHB growth.

PMID- 24025153
TI  - Limitations of MIC as the sole criterion in antimicrobial drug dosage regimen
      design: the need for full characterization of antimicrobial pharmacodynamic
      profile especially for drug-resistant organisms.

PMID- 24025152
TI  - Inhibiting signal transducer and activator of transcription-3 increases response
      to gemcitabine and delays progression of pancreatic cancer.
AB  - BACKGROUND: Among the solid tumors, human pancreatic ductal adenocarcinoma (PDAC)
      has the worst prognosis. Gemcitabine is the standard first line of therapy for
      pancreatic cancer but has limited efficacy due to inherent or rapid development
      of resistance and combining EGFR inhibitors with this regimen results in only a
      modest clinical benefit. The goal of this study was to identify molecular targets
      that are activated during gemcitabine therapy alone or in combination with an
      EGFR inhibitor. METHODS: PDAC cell lines were used to determine molecular changes
      and rates of growth after treatment with gemcitabine or an EGFR inhibitor,
      AG1478, by Western blot analysis and MTT assays respectively. Flow cytometric
      analysis was performed to study the cell cycle progression and rate of apoptosis
      after gemcitabine treatment. ShRNA was used to knockdown STAT3. An in vivo
      orthotopic animal model was used to evaluate STAT3 as a target.
      Immunohistochemical analysis was performed to analyze Ki67 and STAT3 expression
      in tumors. RESULTS: Treatment with gemcitabine increased the levels of
      EGFRTyr1068 and ERK phosphorylation in the PDAC cell lines tested. The
      constitutive STAT3Tyr705 phosphorylation observed in PDAC cell lines was not
      altered by treatment with gemcitabine. Treatment of cells with gemcitabine or
      AG1478 resulted in differential rate of growth inhibition. AG1478 efficiently
      blocked the phosphorylation of EGFRTyr1068 and inhibited the phosphorylation of
      down-stream effectors AKT and ERKs, while STAT3Tyr705 phosphorylation remained
      unchanged. Combining these two agents neither induced synergistic growth
      suppression nor inhibited STAT3Tyr705 phosphorylation, thus prompting further
      studies to assess whether targeting STAT3 improves the response to gemcitabine or
      AG1478. Indeed, knockdown of STAT3 increased sensitivity to gemcitabine by
      inducing pro-apoptotic signals and by increasing G1 cell cycle arrest. However,
      knockdown of STAT3 did not enhance the growth inhibitory potential of AG1478. In
      vivo orthotopic animal model results show that knockdown of STAT3 caused a
      significant reduction in tumor burden and delayed tumor progression with
      increased response to gemcitabine associated with a decrease in the Ki-67
      positive cells. CONCLUSIONS: This study suggests that STAT3 should be considered
      an important molecular target for therapy of PDAC for enhancing the response to
      gemcitabine.

PMID- 24025154
TI  - Regulatory role of miRNAs in polyamine gene expression in the prefrontal cortex
      of depressed suicide completers.
AB  - MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important
      role in the post-transcriptional regulation of mRNA. These molecules have been
      the subject of growing interest as they are believed to control the regulation of
      a large number of genes, including those expressed in the brain. Evidence
      suggests that miRNAs could be involved in the pathogenesis of neuropsychiatric
      disorders. Alterations in metabolic enzymes of the polyamine system have been
      reported to play a role in predisposition to suicidal behaviour. We have
      previously shown the expression of the polyamine genes SAT1 and SMOX to be down
      regulated in the brains of suicide completers. In this study, we hypothesized
      that the dysregulation of these genes in depressed suicide completers could be
      influenced by miRNA post-transcriptional regulation. Using a stringent target
      prediction analysis, we identified several miRNAs that target the 3'UTR of SAT1
      and SMOX. We profiled the expression of 10 miRNAs in the prefrontal cortex (BA44)
      of suicide completers (N = 15) and controls (N = 16) using qRT-PCR. We found that
      several miRNAs showed significant up-regulation in the prefrontal cortex of
      suicide completers compared to psychiatric healthy controls. Furthermore, we
      demonstrated a significant correlation between these miRNAs and the expression
      levels of both SAT1 and SMOX. Our results suggest a relationship between miRNAs
      and polyamine gene expression in the suicide brain, and postulate a mechanism for
      SAT1 and SMOX down-regulation by post-transcriptional activity of miRNAs. 

PMID- 24025156
TI  - Long-term information and distributed neural activation are relevant for the
      "internal features advantage" in face processing: electrophysiological and source
      reconstruction evidence.
AB  - In face processing tasks, prior presentation of internal facial features, when
      compared with external ones, facilitates the recognition of subsequently
      displayed familiar faces. In a previous ERP study (Olivares & Iglesias, 2010) we
      found a visibly larger N400-like effect when identity mismatch familiar faces
      were preceded by internal features, as compared to prior presentation of external
      ones. In the present study we contrasted the processing of familiar and
      unfamiliar faces in the face-feature matching task to assess whether the so
      called "internal features advantage" relies mainly on the use of stored face
      identity-related information or if it might operate independently from stimulus
      familiarity. Our participants (N = 24) achieved better performance with internal
      features as primes and, significantly, with familiar faces. Importantly, ERPs
      elicited by identity mismatch complete faces displayed a negativity around 300
      600 msec which was clearly enhanced for familiar faces primed by internal
      features when compared with the other experimental conditions. Source
      reconstruction showed incremented activity elicited by familiar stimuli in both
      posterior (ventral occipitotemporal) and more anterior (parahippocampal (ParaHIP)
      and orbitofrontal) brain regions. The activity elicited by unfamiliar stimuli
      was, in general, located in more posterior regions. Our findings suggest that the
      activation of multiple neural codes is required for optimal individuation in face
      feature matching and that a cortical network related to long-term information for
      face-identity processing seems to support the internal feature effect.

PMID- 24025155
TI  - A systematic review of the effectiveness of mental health promotion interventions
      for young people in low and middle income countries.
AB  - BACKGROUND: This systematic review provides a narrative synthesis of the evidence
      on the effectiveness of mental health promotion interventions for young people in
      low and middle-income countries (LMICs). Commissioned by the WHO, a review of the
      evidence for mental health promotion interventions across the lifespan from early
      years to adulthood was conducted. This paper reports on the findings for
      interventions promoting the positive mental health of young people (aged 6-18
      years) in school and community-based settings. METHODS: Searching a range of
      electronic databases, 22 studies employing RCTs (N = 11) and quasi-experimental
      designs conducted in LMICs since 2000 were identified. Fourteen studies of school
      based interventions implemented in eight LMICs were reviewed; seven of which
      included interventions for children living in areas of armed conflict and six
      interventions of multicomponent lifeskills and resilience training. Eight studies
      evaluating out-of-school community interventions for adolescents were identified
      in five countries. Using the Effective Public Health Practice Project (EPHPP)
      criteria, two reviewers independently assessed the quality of the evidence.
      RESULTS: The findings from the majority of the school-based interventions are
      strong. Structured universal interventions for children living in conflict areas
      indicate generally significant positive effects on students' emotional and
      behavioural wellbeing, including improved self-esteem and coping skills. However,
      mixed results were also reported, including differential effects for gender and
      age groups, and two studies reported nonsignficant findings. The majority of the
      school-based lifeskills and resilience programmes received a moderate quality
      rating, with findings indicating positive effects on students' self-esteem,
      motivation and self-efficacy. The quality of evidence from the community-based
      interventions for adolescents was moderate to strong with promising findings
      concerning the potential of multicomponent interventions to impact on youth
      mental health and social wellbeing. CONCLUSIONS: The review findings indicate
      that interventions promoting the mental health of young people can be implemented
      effectively in LMIC school and community settings with moderate to strong
      evidence of their impact on both positive and negative mental health outcomes.
      There is a paucity of evidence relating to interventions for younger children in
      LMIC primary schools. Evidence for the scaling up and sustainability of mental
      health promotion interventions in LMICs needs to be strengthened.

PMID- 24025157
TI  - Molecular characterisation of virus in the brains of patients with measles
      inclusion body encephalitis (MIBE).
AB  - BACKGROUND: During 2009/10 a major measles epidemic caused by genotype B3
      occurred in South Africa. Measles inclusion body encephalitis (MIBE) was
      diagnosed in a number of highly immuno-compromised HIV patients. The diagnosis
      was based on typical clinical and MRI findings and positive measles virus PCR in
      brain or CSF.To characterize the brain virus, nucleoprotein, matrix, fusion and
      haemagglutinin genes from 4 cases was compared with virus from acutely infected
      patients. METHODS: cDNA was synthesized using random primers and viral genes were
      amplified by nested RT-PCR. PCR products were sequenced in the forward and
      reverse direction and a contig of each gene was created. Sequences were aligned
      with reference sequences from GenBank and other local sequences. RESULTS: Brain
      virus was very similar to the South African epidemic virus. Features
      characteristic of persistent measles virus in the brain were absent. Mutation
      frequency in brain virus was similar to epidemic virus and had the same
      substitution preference (U to C and C to U). The virus of 2 patients had the same
      L454W mutation in the fusion protein. CONCLUSION: The brain virus was very
      similar to the epidemic strain. The relatively few mutations probably reflect the
      short time from infection to brain disease in these highly immuno-compromised
      patients.

PMID- 24025158
TI  - STEAP1 protein overexpression is an independent marker for biochemical recurrence
      in prostate carcinoma.
AB  - AIMS: To investigate the prognostic value of expression levels of the genes
      STEAP1 and STEAP2, and of STEAP1 protein, in prostate carcinomas (PCa). METHODS
      AND RESULTS: STEAP1 and STEAP2 transcript levels were evaluated by RT-qPCR in
      samples from 35 PCa, 24 adjacent non-neoplastic prostate (AdjP) tissues, five
      cases of benign prostatic hyperplasia (BPH), and two histologically normal
      prostates (N). STEAP1 expression was assessed by immunohistochemistry in samples
      from 198 PCa, 76 AdjP, 22 BPH, and two N. The findings were compared with
      clinical and pathological parameters and patient outcome. STEAP1 and STEAP2
      transcript analysis showed no differences between the groups tested. Although not
      significant, higher STEAP1 mRNA levels were detected in tumours with high Gleason
      scores and in patients who presented with biochemical recurrence (BCR). STEAP1
      overexpression was detected in PCa, and was significantly associated with high
      grade Gleason scores, seminal vesicle invasion, BCR, and worse outcome
      (metastasis or PCa-specific death). STEAP1 overexpression was significantly
      associated with shorter BCR-free survival. Multivariate analysis revealed that
      STEAP1 is an independent marker for BCR. CONCLUSIONS: These findings provide
      evidence that STEAP1 is a biomarker of worse prognosis in PCa patients.

PMID- 24025159
TI  - Influence of biphasic beta-TCP with and without the use of collagen membranes on
      bone healing of surgically critical size defects. A radiological, histological,
      and histomorphometric study.
AB  - OBJECTIVES: The aim of this study was to investigate, by means of radiological
      and histomorphometric analysis, the effect of resorbable collagen membranes on
      critical size defects (CSD) in rabbit tibiae filled with biphasic calcium
      phosphate. MATERIALS AND METHODS: Three CSD of 6 mm diameter were created in both
      tibiae of 20 New Zealand rabbits and divided into three groups according to the
      filling material: Group A (Ossceram), Group B (Ossceram plus Alveoprotect
      membrane), and Group C (unfilled control group). Five animals from each group
      were sacrificed after 15, 30, 45, and 60 days. Anteroposterior and lateral
      radiographs were taken. Samples were processed for observation under light
      microscopy. RESULTS: At the end of treatment, radiological analysis found that
      cortical defect closure was greater in Group B than Group A, and radiopacity was
      clearly lower and more heterogeneous in the Group A cortical defects than in
      Group B. There was no cortical defect closure in Group C. Histomorphometric
      evaluation showed significant differences in newly formed bone and cortical
      closure in Group B compared with Groups A and C, with the presence of higher
      density newly formed bone in cortical and medullar zones. There was no cortical
      defect closure or medullar bone formation in Group C. CONCLUSIONS: Biphasic
      calcium phosphate functioned well as a scaffolding material allowing mineralized
      tissue formation. Furthermore, the addiction of absorbable collagen membranes
      enhanced bone gain compared with non-membrane-treated sites.

PMID- 24025160
TI  - Role of sensory modality and motor planning in the slowing of patients with
      traumatic brain injury: a meta-analysis.
AB  - Here we present a meta-analysis of studies that examined the reaction times (RT)
      of patients with traumatic brain injury (TBI) on decision tasks carried out under
      time pressure. To detect the presence of global components in the data describing
      the slowing of TBI patients, we used predictions of the difference engine model
      (DEM). According to this model, performance can be understood by referring to two
      separate and independent compartments, one cognitive and one sensory-motor.
      Results confirm previous observations that TBI patients are delayed with respect
      to matched controls by a multiplicative factor affecting performance over and
      above the specific characteristics of the tasks. This meta-analysis also shows
      that the global factor affecting TBI patients' performance is selective for the
      visual modality. No over-additivity was detected on tasks in the acoustic
      modality. Estimates of the time taken by the sensory-motor component of the task
      indicated substantial slowing in the TBI patients. This delay was particularly
      marked in patients with severe TBI. 

PMID- 24025161
TI  - Highly conserved base A55 of 16S ribosomal RNA is important for the elongation
      cycle of protein synthesis.
AB  - Accurate decoding of mRNA requires the precise interaction of protein factors and
      tRNAs with the ribosome. X-ray crystallography and cryo-electron microscopy have
      provided detailed structural information about the 70S ribosome with protein
      factors and tRNAs trapped during translation. Crystal structures showed that one
      of the universally conserved 16S rRNA bases, A55, in the shoulder domain of the
      30S subunit interacts with elongation factors Tu and G (EF-Tu and EF-G,
      respectively). The exact functional role of A55 in protein synthesis is not
      clear. We changed A55 to U and analyzed the effect of the mutation on the
      elongation cycle of protein synthesis using functional assays. Expression of 16S
      rRNA with the A55U mutation in cells confers a dominant lethal phenotype.
      Additionally, ribosomes with the A55U mutation in 16S rRNA show substantially
      reduced in vitro protein synthesis activity. Equilibrium binding studies showed
      that the A55U mutation considerably inhibited the binding of the EF-Tu.GTP.tRNA
      ternary complex to the ribosome. Furthermore, the A55U mutation slightly
      inhibited the peptidyl transferase reaction, the binding of EF-G.GTP to the
      ribosome, and mRNA-tRNA translocation. These results indicate that A55 is
      important for fine-tuning the activity of the ribosome during the elongation
      cycle of protein synthesis.

PMID- 24025162
TI  - Molecular networking as a dereplication strategy.
AB  - A major goal in natural product discovery programs is to rapidly dereplicate
      known entities from complex biological extracts. We demonstrate here that
      molecular networking, an approach that organizes MS/MS data based on chemical
      similarity, is a powerful complement to traditional dereplication strategies.
      Successful dereplication with molecular networks requires MS/MS spectra of the
      natural product mixture along with MS/MS spectra of known standards, synthetic
      compounds, or well-characterized organisms, preferably organized into robust
      databases. This approach can accommodate different ionization platforms, enabling
      cross correlations of MS/MS data from ambient ionization, direct infusion, and LC
      based methods. Molecular networking not only dereplicates known molecules from
      complex mixtures, it also captures related analogues, a challenge for many other
      dereplication strategies. To illustrate its utility as a dereplication tool, we
      apply mass spectrometry-based molecular networking to a diverse array of marine
      and terrestrial microbial samples, illustrating the dereplication of 58 molecules
      including analogues. 

PMID- 24025164
TI  - Silver-catalyzed radical phosphonofluorination of unactivated alkenes.
AB  - We report herein a mild and catalytic phosphonofluorination of unactivated
      alkenes. With catalysis by AgNO3, the condensation of various unactivated alkenes
      with diethyl phosphite and Selectfluor reagent in CH2Cl2/H2O/HOAc at 40  degrees
      C led to the efficient synthesis of beta-fluorinated alkylphosphonates with good
      stereoselectivity and wide functional group compatibility. A mechanism involving
      silver-catalyzed oxidative generation of phosphonyl radicals and silver-assisted
      fluorine atom transfer is proposed. 

PMID- 24025163
TI  - Asymmetric cross-dehydrogenative coupling enabled by the design and application
      of chiral triazole-containing phosphoric acids.
AB  - This report describes the development of an enantioselective C-N bond-forming
      reaction to produce 1,2,3,4-tetrahydroisoquinoline-derived cyclic aminals
      catalyzed by chiral phosphate anions. Central to the success of this goal was the
      design of a library of 3,3'-triazolyl BINOL-derived phosphoric acids capable of
      forming attractive hydrogen-bonding interactions with the peptide-like substrate.
      We envision this work will offer an alternative to the conventional strategy of
      increasing catalyst steric bulk to improve enantioselectivity with BINOL-derived
      phosphoric acids. 

PMID- 24025165
TI  - Functional nucleic acid entrapment in sol-gel derived materials.
AB  - Functional nucleic acids (FNAs) are single-stranded DNA or RNA molecules,
      typically generated through in vitro selection, that have the ability to act as
      receptors for target molecules (aptamers) or perform catalysis of a chemical
      reaction (deoxyribozymes and ribozymes). Fluorescence-signaling aptamers and
      deoxyribozymes have recently emerged as promising biological recognition and
      signaling elements, although little has been done to evaluate their potential for
      solid-phase assays, particularly with species made of RNA due to their lack of
      chemical stability and susceptibility to nuclease attack. Herein, we present a
      detailed overview of the methods utilized for solid-phase immobilization of FNAs
      using a sol-gel entrapment method that can provide protection from nuclease
      degradation and impart long-term chemical stability to the FNA reporter systems,
      while maintaining their signaling capabilities. This article will also provide a
      brief review of the results of such entrapment studies involving fluorescence
      signaling versions of a DNA aptamer, selected RNA-cleaving deoxyribozymes, and
      two different RNA aptamers in a series of sol-gel derived composites, ranging
      from highly polar silica to hydrophobic methylsilsesquioxane-based materials.
      Given the ability to produce sol-gel derived materials in a variety of
      configurations, particularly as thin film coatings on electrodes, optical fibers,
      and other devices, this entrapment method should provide a useful platform for
      numerous solid-phase FNA-based biosensing applications.

PMID- 24025167
TI  - ESR and optical study of photo-orientation in azobenzene-containing liquid
      crystalline polymer.
AB  - We report a comprehensive experimental study of photoinduced processes in
      azobenzene-containing liquid-crystalline polymer. The kinetic and optical
      characteristics of the photoisomerization reaction and photo-orientation process
      have been determined. The spin probe technique has been used to elucidate the
      details of orientation order and rotational mobility of molecular fragments
      within the liquid-crystalline polymer. The evolution of orientation order
      parameters <P2>, <P4>, and <P6> in the course of photoinduced ordering of the
      material as well as the change of liquid-crystalline domain sizes have been
      studied quantitatively. The obtained experimental results are compared with the
      predictions of the existing models of photo-orientation.

PMID- 24025166
TI  - Role of HGF in epithelial-stromal cell interactions during progression from
      benign breast disease to ductal carcinoma in situ.
AB  - INTRODUCTION: Basal-like and luminal breast cancers have distinct stromal
      epithelial interactions, which play a role in progression to invasive cancer.
      However, little is known about how stromal-epithelial interactions evolve in
      benign and pre-invasive lesions. METHODS: To study epithelial-stromal
      interactions in basal-like breast cancer progression, we cocultured reduction
      mammoplasty fibroblasts with the isogenic MCF10 series of cell lines
      (representing benign/normal, atypical hyperplasia, and ductal carcinoma in situ).
      We used gene expression microarrays to identify pathways induced by coculture in
      premalignant cells (MCF10DCIS) compared with normal and benign cells (MCF10A and
      MCF10AT1). Relevant pathways were then evaluated in vivo for associations with
      basal-like subtype and were targeted in vitro to evaluate effects on
      morphogenesis. RESULTS: Our results show that premalignant MCF10DCIS cells
      express characteristic gene expression patterns of invasive basal-like
      microenvironments. Furthermore, while hepatocyte growth factor (HGF) secretion is
      upregulated (relative to normal, MCF10A levels) when fibroblasts are cocultured
      with either atypical (MCF10AT1) or premalignant (MCF10DCIS) cells, only MCF10DCIS
      cells upregulated the HGF receptor MET. In three-dimensional cultures,
      upregulation of HGF/MET in MCF10DCIS cells induced morphological changes
      suggestive of invasive potential, and these changes were reversed by antibody
      based blocking of HGF signaling. These results are relevant to in vivo
      progression because high expression of a novel MCF10DCIS-derived HGF signature
      was correlated with the basallike subtype, with approximately 86% of basal-like
      cancers highly expressing the HGF signature, and because high expression of HGF
      signature was associated with poor survival. CONCLUSIONS: Coordinated and
      complementary changes in HGF/MET expression occur in epithelium and stroma during
      progression of pre-invasive basal-like lesions. These results suggest that
      targeting stroma-derived HGF signaling in early carcinogenesis may block
      progression of basal-like precursor lesions.

PMID- 24025168
TI  - Impact of neonatal NOS-1 inhibitor exposure on neurobehavioural measures and
      prefrontal-temporolimbic integration in the rat nucleus accumbens.
AB  - Nitric oxide (NO) is a gaseous neurotransmitter that plays a significant role in
      the establishment and refinement of functional neural circuits. Genetic and post
      mortem studies have suggested that neuronal NO synthase (NOS-1) activity may be
      compromised in frontal and temporal lobes, and related structures, in
      schizophrenia. The goal of this study was to determine if there is a link between
      neonatal disruptions in NO signalling and disturbances in the development and
      function of prefrontal-temporolimbic circuits. Neonatal rats were injected on
      postnatal days PD3-5 with the selective NOS-1 inhibitor Nomega-propyl-L-arginine
      (NPA) and tested in adulthood (>=PD60) or as juveniles (PD30). Adult rats treated
      with NPA as neonates exhibited increased amphetamine-induced locomotion compared
      to animals receiving vehicle as neonates, whereas this was not observed in
      juvenile rats treated with NPA as neonates. Adult rats exposed to NPA as neonates
      also exhibited deficits in social interaction and short-term recognition memory,
      as well as reduced brain weight, compared to vehicle-treated controls. Finally,
      neonatal NPA exposure increased the responsiveness of nucleus accumbens neurons
      to prefrontal cortical input and disrupted the modulation of cortico-accumbens
      circuits by hippocampal afferents that is normally observed in adult animals.
      These results show for the first time that neonatal inhibition of NOS-1 during a
      critical neurodevelopmental period leads to aberrant behaviours that manifest in
      adulthood, as well as electrophysiological abnormalities in prefrontal
      temporolimbic circuits. Greater understanding of the role of NOS-1 in the
      development of these circuits will shed light on how developmental insults
      translate to pathophysiology associated with schizophrenia.

PMID- 24025169
TI  - Novel carbazole-phenothiazine dyads for dye-sensitized solar cells: a combined
      experimental and theoretical study.
AB  - We report a joint experimental and computational work on new organic donor
      acceptor dye sensitizers in which a carbazole (CZ) and a phenothiazine (PTZ)
      units are linked together by an alkyl C6H13, while two different anchoring groups
      are employed: the cyanoacrylic acid (CS1A, CSORG1) and the rhodanine-3-acetic
      acid (CS4A, CSORG4). The CZ moiety has multiple roles of (i) acting as an extra
      electron donor portion, providing more electron density on the PTZ; (ii)
      suppressing the back-electron transfer from TiO2 to the electrolyte by forming a
      compact insulating dye layer; (iii) modulating dye aggregation on the
      semiconductor surface; and (iv) acting as an antenna, collecting photons and,
      through long-range energy transfer, redirecting the captured energy to the dye
      sensitizer. We show that the introduction of the CZ donor remarkably enhances the
      photovoltaic performances of the rhodanine-based dye, compared to the
      corresponding simple PTZ dye, with more than a two-fold increase in the overall
      efficiencies, while it does not bring beneficial effects in the case of the
      cyanoacrylic-based sensitizer. Based on quantum mechanical calculations and
      experimental measurements, we show that, in addition to a favored long-range
      energy transfer, which increases the light absorption in the blue region of the
      spectrum, the presence of the CZ unit in the CSORG4 dye effectively induces a
      beneficial aggregation pattern on the semiconductor surface, yielding a broadened
      and red-shifted light absorption, accounting for the two-fold increase in the
      generated photocurrent. 

PMID- 24025170
TI  - [Physical training in the elderly].

PMID- 24025171
TI  - [Atrioventricular nodal re-entry tachycardia].

PMID- 24025173
TI  - [Sarcopenia: definition, diagnostics and therapy].
AB  - Sarcopenia is an age-related generalized loss of muscle mass and muscle strength
      resulting in low physical performance. It can be observed in up to 50% of >80
      year old men and women. Sarcopenia is strongly linked to frailty and causes
      physical disability, falls and institutionalization. Degenerative processes in
      the neuromuscular system, reduced food intake and physical inactivity are the
      most important causes. To screen for sarcopenia, gait speed should be measured.
      If gait speed is below 0,8 m/s, further diagnostics are indicated. Muscle mass
      can be assessed for instance by using DEXA (Dual Energy X-Ray Absorptiometry),
      Muscle strength with the "Handgrip Strength Test" and physical performance using
      a clinical test survey ("Chair Stand Test"). A Therapy is indicated if
      measurements are below defined cut off points in all three tests. Studies showed
      that the best way to improve sarcopenia is the combination of power or high
      velocity resistance training with leucin-rich protein supplementation. 

PMID- 24025174
TI  - [Between threat and hope - fertility preservation in young cancer patients].
AB  - Recent advances in cancer therapy have resulted in an increased number of long
      term cancer survivors. Infertility, however, might be the consequence of an
      efficient cancer treatment. For young patients affected by cancer accesses to the
      partly established and partly still experimental options to preserve fertility
      are crucial. As decisions on fertility preservation have to be made in the short
      time period after diagnosis and before onset of cancer treatment, counselling is
      challenging. Based on an overview on technical options to preserve fertility, the
      ethical dilemma will be discussed and the nowadays available study results
      concerning the psychological dimension and the requirements for counselling will
      be presented. Due to the complexity of the topic a multidisciplinary approach
      considering experts' recommendations is indispensable. 

PMID- 24025175
TI  - [Recurrent nephrolithiasis - what next?].
AB  - Nephrolithiasis is a common disease with a high recurrence rate. It is associated
      with a significant morbidity for an individual patient, but also an immense
      socioeconomic burden. A better understanding and recognition of underlying risk
      factors and prevention strategies are therefore of great importance. The
      evaluation for metaphylaxsis consists of a thorough patient history, metabolic
      examination of blood and urine, imaging of the kidney and urinary tract, and
      whenever possible a stone analysis. On the basis of the results, preventative
      measures can be performed. Therapeutic goals in stone prevention are to reduce
      the urine saturation of stone forming salts, to increase the urine concentration
      of stone formation inhibitors, and if necessary, the modification of urine pH. A
      dietary modification is the cornerstone of a successful metaphylaxis. 

PMID- 24025176
TI  - [Chronic cough].
AB  - In non-smokers without intake of an ACE-inhibitor, the three most common causes
      of chronic cough are eosinophilic airways disease (asthma or eosinophilic
      bronchitis), Upper-airway-cough-syndrome (UACS) and Gastro-esophageal-reflux
      desease (GERD). In smokers, chronic bronchitis and COPD are common causes as
      well. In patients with a normal chest X-ray and lack of information on a less
      frequent cause in history and physical examination, it is recommended therefore
      to routinely look for these diseases and/or to treat them empirically. 

PMID- 24025177
TI  - [<<Sterile>> spondylodiscitis].
AB  - We report the case of a 81 year old women presenting with fever and back pain.
      Infectious spondylodiscitis was first supposed due to the imaging of the spine
      although no pathogenic agent could be proved. Antibiotic therapy was initiated.
      Because of the persistence of the symptoms biopsy was repeated, this time done by
      a surgeon. Eventually spinal gout was diagnosed. Symptomatic therapy alone
      removed the discomfort. 

PMID- 24025179
TI  - [Combination therapy in postmenopausal osteoporosis leads to denser bones than
      monotherapy].

PMID- 24025180
TI  - [Preventive antibiotics reduce risk of urinary tract infection after catheter
      removal].

PMID- 24025182
TI  - [CME ECG 42. Chest pain. Takotsubo cardiomyopathy].

PMID- 24025185
TI  - A note on the laboratory culture of the benthic foraminifer Cornuloculina
      balkwilli (MacFadyen).
AB  - BACKGROUND: Genetic studies of the Foraminifera provide valuable insights into
      marine speciation and biogeography, yet the discovery of vitally needed new
      genetic markers for this important group is being severely limited by an extreme
      lack of genetic data. The establishment of a laboratory culture from a single,
      asexually reproducing foraminifer, will be essential to provide enough pooled
      genetic material from these unicellular organisms, to facilitate full genome
      sequencing and genetic marker discovery, using next-generation sequencing
      techniques. FINDINGS: The aim of this study was to develop a simple and
      inexpensive method of culturing benthic foraminifera, via asexual reproduction,
      in a controlled laboratory environment. Individual specimens of the benthic
      foraminfer Cornuloculina balkwilli (MacFadyen) were placed in 7 cm plastic
      beakers, containing 50 ml natural seawater, filtered to 0.2 MUm, and kept at 23
      degrees C, with a 12-hour light/dark cycle, and fed weekly on a mixed algal diet
      of Dunaliella tertiolecta and Phaeodactylum tricornutum. Asexually derived
      cultures were successfully established from 4 specimens of Cornuloculina
      balkwilli, originally added to the culture vessels as immature specimens. Many
      thousands of individuals were present after 6 months. CONCLUSIONS: The method
      presented here demonstrates that only basic laboratory equipment is required to
      establish and maintain a thriving culture of the benthic foraminfer, C.
      balkwilli, from a single asexually reproducing specimen, providing an excellent
      source of genetic material for use in next generation sequencing. The method is
      easily reproducible and will greatly aid in the discovery of critically needed
      new genetic markers in the Foraminifera. It also highlights C. balkwilli as a
      good candidate species for use in the field of environmental micropaleontology.

PMID- 24025187
TI  - Determination of fenvalerate in tomato by ultrasound-assisted solvent extraction
      combined with dispersive liquid-liquid microextraction.
AB  - Ultrasound-assisted solvent extraction (UASE) combined with dispersive liquid
      liquid microextraction based on the solidification of floating organic drop
      (DLLME-SFO) has been developed for extraction and determination of fenvalerate
      from tomato samples. Fenvalerate was determined by high-performance liquid-liquid
      chromatography-ultraviolet detector. Effects of parameters such as type and
      volume of extraction solvent in the UASE stage, sonication time, type and volume
      of extraction solvent and disperser solvent in the DLLME-SFO stage, salt addition
      and pH effect on extraction were studied and optimized. Under the optimum
      conditions, the calibration graph was linear in the range of 5-500 ug kg(-1) with
      a detection limit of 0.6 ug kg(-1). The relative standard deviation for five
      replicate measurements of 100 ug kg(-1) of fenvalerate was 6.5%. The relative
      recovery of fenvalerate in different tomato samples at a spiking level of 10, 20
      and 50 ug kg(-1) is in the range of 93.5-108%. The obtained results show that
      UASE-DLLME-SFO is a sensitive, fast and simple method for the determination of
      fenvalerate in tomato samples. 

PMID- 24025186
TI  - Porphyromonas gingivalis HmuY stimulates expression of Bcl-2 and Fas by human
      CD3+ T cells.
AB  - BACKGROUND: Apoptosis is a highly controlled process of cell death that can be
      induced by periodontopathogens. The present study aimed to investigate the
      expression of Fas and Bcl-2 proteins by CD3+ T cells in vitro under stimulation
      by total Porphyromonas gingivalis antigens and purified recombinant P. gingivalis
      HmuY protein. RESULTS: CD3+ T cells derived from CP patients and stimulated with
      HmuY expressed higher levels of Bcl-2 compared to identical cells stimulated with
      P. gingivalis crude extract or cells derived from NP control subjects (p =
      0.043). CONCLUSION: The authors hypothesize that P. gingivalis HmuY plays a role
      in the pathogenesis of chronic periodontitis, possibly by reducing or delaying
      apoptosis in T cells through a pathway involving the Bcl-2 protein.

PMID- 24025189
TI  - Autonomic dysfunction in patients with arrhythmogenic right ventricular
      cardiomyopathy: biochemical evidence of altered signaling pathways.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an
      important cause of sudden cardiac death especially in times of increased
      sympathetic tone, for example, during sports, which have been confirmed by
      nuclear imaging studies. However, the underlying biochemical pathways remain to
      be delineated. Therefore, we investigated the expression levels of proteins of
      the signaling cascade in patients with ARVC. METHODS: During diagnostic work-up,
      right ventricular endomyocardial biopsies (EMBs) were sampled from 15 consecutive
      male ARVC patients (52 +/- 14 years). Tissue levels of key proteins of the
      signaling cascade were analyzed. Results were compared to those obtained from
      EMBs of 10 patients with idiopathic right ventricular outflow-tract tachycardia
      (RVOT; 41 +/- 14 years) and of five control subjects without identifiable
      structural heart disease (42 +/- 13 years; P = ns). RESULTS: Among the proteins
      analyzed, only tissue levels of norepinephrine (NE; P < 0.04) and cyclic
      adenosine-3',5'-monophospate (cAMP; P < 0.01) were significantly lower in ARVC
      when compared to RVOT patients. When compared to controls, mean cAMP levels were
      lower in patients with ARVC but did not reach statistical significance. No
      differences in cAMP were observed between RVOT and controls. CONCLUSIONS: The
      current findings confirm and expand the concept of adrenergic dysfunction in
      ARVC: the reduction of NE in ARVC could lead to an impaired stimulation of beta
      adrenoceptor subsequent signaling pathways with potential implication for cardiac
      fibrosis and arrhythmogenesis.

PMID- 24025190
TI  - A survey of the reformulation of Australian child-oriented food products.
AB  - BACKGROUND: Childhood obesity is one of the most pressing public health
      challenges of the 21st century. Reformulating commonly eaten food products is a
      key emerging strategy to improve the food supply and help address rising rates of
      obesity and chronic disease. This study aimed to monitor reformulation of
      Australian child-oriented food products (products marketed specifically to
      children) from 2009-2011. METHODS: In 2009, all child-oriented food products in a
      large supermarket in metropolitan Adelaide were identified. These baseline
      products were followed up in 2011 to identify products still available for sale.
      Nutrient content data were collected from Nutrient Information Panels in 2009 and
      2011. Absolute and percentage change in nutrient content were calculated for
      energy, total fat, saturated fat, sugars, sodium and fibre. Data were
      descriptively analysed to examine reformulation in individual products, in key
      nutrients, within product categories and across all products. Two methods were
      used to assess the extent of reformulation; the first involved assessing
      percentage change in single nutrients over time, while the second involved a set
      of nutrient criteria to assess changes in overall healthiness of products over
      time. RESULTS: Of 120 products, 40 remained unchanged in nutrient composition
      from 2009-2011 and 80 underwent change. The proportions of positively and
      negatively reformulated products were similar for most nutrients surveyed, with
      the exception of sodium. Eighteen products (15%) were simultaneously positively
      and negatively reformulated for different nutrients. Using percentage change in
      nutrient content to assess extent of reformulation, nearly half (n = 53) of all
      products were at least moderately reformulated and just over one third (n = 42)
      were substantially reformulated. The nutrient criteria method revealed 5 products
      (6%) that were positively reformulated and none that had undergone negative
      reformulation. CONCLUSION: Positive and negative reformulation was observed to a
      similar extent within the sample indicating little overall improvement in
      healthiness of the child-oriented food supply from 2009-2011. In the absence of
      agreed reformulation standards, the extent of reformulation was assessed against
      criteria developed specifically for this project. While arbitrary in nature,
      these criteria were based on reasonable assessment of the meaningfulness of
      reformulation and change in nutrient composition. As well as highlighting
      nutrient composition changes in a number of food products directed to children,
      this study emphasises the need to develop comprehensive, targeted and
      standardised reformulation benchmarks to assess the extent of reformulation
      occurring in the food supply.

PMID- 24025188
TI  - miR-204 mediated loss of Myeloid cell leukemia-1 results in pancreatic cancer
      cell death.
AB  - BACKGROUND: Pancreatic cancer is one of the most lethal human malignancies, with
      an all-stage 5-year survival of <5%, mainly due to lack of effective available
      therapies. Cancer cell survival is dependent upon up-regulation of the pro
      survival response, mediated by anti-apoptotic proteins such as Mcl-1. RESULTS:
      Here we show that over-expression of Mcl-1 in pancreatic patient tumor samples is
      linked to advancement of the disease. We have previously shown that triptolide, a
      diterpene triepoxide, is effective both in vitro and in vivo, in killing
      pancreatic cancer cells. Decrease of Mcl-1 levels, either by siRNA or by
      treatment with triptolide results in cell death. Using pancreatic cancer cell
      lines, we have shown that miR-204, a putative regulator of Mcl-1, is repressed in
      cancer cell lines compared to normal cells. Over-expression of miR-204, either by
      a miR-204 mimic, or by triptolide treatment results in a decrease in Mcl-1
      levels, and a subsequent decrease in cell viability. Using luciferase reporter
      assays, we confirmed the ability of miR-204 to down-regulate Mcl-1 by directly
      binding to the Mcl-1 3' UTR. Using human xenograft samples treated with
      Minnelide, a water soluble variant of triptolide, we have shown that miR-204 is
      up-regulated and Mcl-1 is down-regulated in treated vs. control tumors.
      CONCLUSION: Triptolide mediated miR-204 increase causes pancreatic cancer cell
      death via loss of Mcl-1.

PMID- 24025191
TI  - Subjective Well-Being Under Neuroleptics Scale short form (SWN-K): reliability
      and validity in an Estonian speaking sample.
AB  - BACKGROUND: The Subjective Well-Being Under Neuroleptic Treatment Scale short
      form (SWN-K) is a self-rating scale developed to measure mentally ill patients'
      well-being under the antipsychotic drug treatment. This paper reports on
      adaptation and psychometric properties of the instrument in an Estonian
      psychiatric sample. METHODS: In a naturalistic study design, 124 inpatients or
      outpatients suffering from the first psychotic episode or chronic psychotic
      illness completed the translated SWN-K instrument. Item content analysis,
      internal consistency analysis, exploratory principal components analysis, and
      confirmatory factor analysis were used to construct the Estonian version of the
      SWN-K (SWN-K-E). Additionally, socio-demographic and clinical data, observer
      rated psychopathology, medication side effects, daily antipsychotic drug dosages,
      and general functioning were assessed at two time points, at baseline and after a
      29-week period; the associations of the SWN-K-E scores with these variables were
      explored. RESULTS: After having selected 20 items for the Estonian adaptation,
      the internal consistency of the total SWN-K-E was 0.93 and the subscale
      consistencies ranged from 0.70 to 0.80. Good test-retest reliabilities were
      observed for the adapted scale scores, with the correlation of the total score
      over about 6 months being r = 0.70. Confirmatory factor analysis replicated the
      presence of a higher-order factor (general well-being) and five first-order
      factors (mental functioning, physical functioning, social integration, emotional
      regulation, and self-control); the model fitted the data well. The results
      indicated a moderate-high correlations r = 0.54 between the SWN-K-E total score
      and the evaluation how satisfied patients were with their lives in generally. No
      significant correlations were found between the overall subjective well-being
      score and age, severity of the psychopathology, drug adverse effects, or
      prescribed drug dosage. CONCLUSION: Taken together, the results demonstrated that
      the Estonian version of the SWN-K is a reliable and valid instrument with
      psychometric properties similar to the original English version. The potential
      uses of the scale in both research and clinical settings are considered.

PMID- 24025192
TI  - Ruthenium-catalyzed regioselective C2 alkenylation of indoles and pyrroles via C
      H bond functionalization.
AB  - An efficient ruthenium-catalyzed oxidative coupling of indoles and pyrroles with
      various alkenes at the C2-position assisted by employing the N,N
      dimethylcarbamoyl moiety as a directing group is reported. The catalytic reaction
      proceeds in an excellent regio- and stereoselective manner. 

PMID- 24025193
TI  - A new platform for constructing antibody-cytokine fusion proteins
      (immunocytokines) with improved biological properties and adaptable cytokine
      activity.
AB  - A novel method for constructing immunocytokines has been developed that utilizes
      fusion of cytokines to the C-terminus of the Ig light chain, rather than fusing
      to the heavy chain. Such molecules are expressed well in transfected cells, are
      very stable in normal buffers and have biological properties that are superior to
      immunocytokines made by fusion to the heavy chain. These properties include
      longer circulating half-life, increased uptake following subcutaneous dosing and
      similar or improved antibody effector activities of antibody-dependent cytotoxic
      activity and complement-dependent cytotoxicity, respectively. Furthermore, the
      sequestering effect of this fusion junction allows one to adjust intermediate
      affinity (betagamma) interleukin 2 receptor (IL2R) binding and activation by
      shortening the N-terminus of IL2 at the fusion point. This appears to limit
      access of the critical contact residue Asp20 of IL2 to the beta-chain of
      betagamma IL2R, while maintaining binding and activation of high-affinity
      (alphabetagamma) IL2R-expressing cells. Several immunocytokine forms with varying
      degrees of IL2R specificity have been constructed, and some appear to regain
      their activity for the betagamma IL2R when bound to antigen-coated beads. Such
      molecules may have reduced toxicity in the circulation and enhanced anti-tumor
      activity. 

PMID- 24025194
TI  - Individual responsibility, solidarity and differentiation in healthcare.
AB  - OBJECTIVES: Access to healthcare in most western societies is based on equality.
      Rapidly rising costs have fuelled debates about differentiation in access to
      healthcare. We assessed the public's perceptions and attitudes about
      differentiation in healthcare according to lifestyle behaviour. METHODS: A
      vignette study was undertaken in participants in a colorectal cancer screening
      pilot programme in the Netherlands. Screenees with a negative test result
      received a questionnaire in which nine hypothetical situations were described:
      three different healthcare settings (screening, lung cancer, chronic obstructive
      pulmonary disease) combined with three forms of differentiation each: a
      difference in premium, waiting list ordering or copayment according to lifestyle.
      We evaluated the responses using a general hierarchical linear model. RESULTS:
      The percentage of participants in agreement with differentiation varied from 20%
      to 58% (overall mean of 40%). Significantly more participants were in favour of
      giving a premium discount to those who do not engage in unhealthy behaviour
      compared with supporters for higher payments for those who do. More
      differentiation was supported for non-smoking versus smoking cessation than for
      participation versus non-participation in screening. We observed in-group
      favouritism in smokers, but no significant effects of age or disease. There was
      no support for waiting list ordering based on lifestyle. CONCLUSIONS: Results of
      this study show that Dutch citizens eligible for colorectal cancer screening are
      in favour of some form of financial differentiation in the distribution of
      healthcare, but that significant differences exist between type of setting and
      the type of behaviour. Our study can be used in the ongoing discussion about
      solidarity and behaviour in healthcare.

PMID- 24025195
TI  - Rh2(R-TPCP)4-catalyzed enantioselective [3+2]-cycloaddition between nitrones and
      vinyldiazoacetates.
AB  - Rhodium-catalyzed reaction of vinyldiazoacetates with nitrones results in a
      formal [3+2]-cycloaddition to generate 2,5-dihydroisoxazoles with high levels of
      asymmetric induction. The cascade reaction begins with a vinylogous addition
      event, followed by an iminium addition ring-closure/hydride migration/alkene
      isomerization cascade. Dirhodium tetrakis(triarylcyclopropanecarboxylates) are
      the optimum catalysts for this process. 

PMID- 24025196
TI  - Impact on survival of whole-body computed tomography before emergency bleeding
      control in patients with severe blunt trauma.
AB  - INTRODUCTION: Whole-body computed tomography (CT) has gained importance in the
      early diagnostic phase of trauma care. However, the diagnostic value of CT for
      seriously injured patients is not thoroughly clarified. This study assessed
      whether preoperative CT beneficially affected survival of patients with blunt
      trauma who required emergency bleeding control. METHODS: This retrospective study
      was conducted from January 2004 to December 2010 in two tertiary trauma centers
      in Japan. The primary inclusion criterion was patients with blunt trauma who
      required emergency bleeding control (surgery or transcatheter arterial
      embolization). CT before emergency bleeding control was performed at the
      attending physician's discretion based on individual patient condition (for
      example, hemodynamic stability or certain abnormalities in the primary survey).
      We assessed covariates associated with 28-day mortality with multivariate
      logistic regression analysis and evaluated standardized mortality ratio (SMR,
      ratio of observed to predicted mortality by Trauma and Injury Severity Score
      (TRISS) method) in two subgroups of patients who did or did not undergo CT.
      RESULTS: The inclusion criterion was fulfilled by 152 patients with a median
      Injury Severity Score of 35.3. During the early resuscitation phase, 132 (87%)
      patients underwent CT and 20 (13%) did not. Severity of injury was significantly
      higher in the non-CT versus CT group patients. Observed mortality rate was
      significantly lower in the CT versus non-CT group (18% vs. 80%, P <0.001).
      Multivariate adjustment for the probability of survival (Ps) by TRISS method
      confirmed CT as an independent predictor for 28-day mortality (adjusted OR, 7.22;
      95% CI, 1.76 to 29.60; P = 0.006). In the subgroup with less severe trauma (TRISS
      Ps >=50%), SMR in the CT group was 0.63 (95% CI, 0.23 to 1.03; P = 0.066),
      indicating no significant difference between observed and predicted mortality in
      the CT group. In contrast, in the subgroup with more severe trauma (TRISS Ps
      <50%), SMR was 0.65 (95% CI, 0.41 to 0.90; P = 0.004) only in the CT group,
      whereas the difference between observed and predicted mortality was not
      significant in the non-CT group, suggesting a possible beneficial effect of CT on
      survival only in trauma patients at high risk of death. CONCLUSION: CT performed
      before emergency bleeding control might be associated with improved survival,
      especially in severe trauma patients with TRISS Ps of <50%.

PMID- 24025199
TI  - Azobenzene-functionalized gold nanoparticles as hybrid double-floating-gate in
      pentacene thin-film transistors/memories with enhanced response, retention, and
      memory windows.
AB  - Gold nanoparticles (Au-NPs) with surfaces covered with a self-assembled monolayer
      of azobenzene derivatives were prepared at the interface of dielectric insulator
      SiO2 and pentacene thin film. Transistors constructed with these composite
      channel materials exhibited electric bistability upon different gate biases, with
      the monolayer serving as a barrier layer, a work function modulator, as well as
      additional charge trapping sites at the Au-NPs/semiconductor interface at the
      same time. In comparison with simple alkanethiol monolayer-covered Au-NPs, the
      CH3-substituted azobenzene-functionalized Au-NPs result in a transistor memory
      device with about 70% more charges trapped, much faster response time as well as
      higher retention time. Besides, depending on the substituent on the azobenzene
      moieties (CH3, H, or CF3) and the tethering alkyl chain length, the speed at
      which the carriers are trapped (affecting switching response) and the stability
      of the carriers that are trapped (affecting memory retention) can be modulated to
      improve the device performance. The structural characterization and electronic
      characteristics of these devices will be detailed. 

PMID- 24025198
TI  - A Web-based interactive diabetes registry for health care management and planning
      in Saudi Arabia.
AB  - BACKGROUND: Worldwide, eHealth is a rapidly growing technology. It provides good
      quality health services at lower cost and increased availability. Diabetes has
      reached an epidemic stage in Saudi Arabia and has a medical and economic impact
      at a countrywide level. Data are greatly needed to better understand and plan to
      prevent and manage this medical problem. OBJECTIVE: The Saudi National Diabetes
      Registry (SNDR) is an electronic medical file supported by clinical,
      investigational, and management data. It functions as a monitoring tool for
      medical, social, and cultural bases for primary and secondary prevention
      programs. Economic impact, in the form of direct or indirect cost, is part of the
      registry's scope. The registry's geographic information system (GIS) produces a
      variety of maps for diabetes and associated diseases. In addition to availability
      and distribution of health facilities in the Kingdom, GIS data provide health
      planners with the necessary information to make informed decisions. The
      electronic data bank serves as a research tool to help researchers for both
      prospective and retrospective studies. METHODS: A Web-based interactive GIS
      system was designed to serve as an electronic medical file for diabetic patients
      retrieving data from medical files by trained registrars. Data was audited and
      cleaned before it was archived in the electronic filing system. It was then used
      to produce epidemiologic, economic, and geographic reports. A total of 84,942
      patients were registered from 2000 to 2012, growing by 10% annually. RESULTS: The
      SNDR reporting system for epidemiology data gives better understanding of the
      disease pattern, types, and gender characteristics. Part of the reporting system
      is to assess quality of health care using different parameters, such as HbA1c,
      that gives an impression of good diabetes control for each institute. Economic
      reports give accurate cost estimation of different services given to diabetic
      patients, such as the annual insulin cost per patient for type 1, type 2, and
      gestational diabetes, which are 1155 SR (US $308), 1406 SR (US $375), and 1002 SR
      (US $267), respectively. Of this, 72.02% of the total insulin cost is spent on
      type 2 patients and 55.39% is in the form of premixed insulin. The SNDR can
      provide an accurate assessment of the services provided for research purposes.
      For example, only 27.00% of registered patients had an ophthalmic examination and
      only 71.10% of patients with proliferative retinopathy had laser therapy.
      CONCLUSIONS: The SNDR is an effective electronic medical file that can provide
      epidemiologic, economic, and geographic reports that can be used for disease
      management and health care planning. It is a useful tool for research and disease
      health care quality monitoring.

PMID- 24025197
TI  - Prostaglandin E(2) in tick saliva regulates macrophage cell migration and
      cytokine profile.
AB  - BACKGROUND: Ticks are obligate hematophagous ectoparasites that suppress the
      host's immune and inflammatory responses by secreting immuno-modulatory and anti
      inflammatory molecules in their saliva. In previous studies we have shown that
      tick salivary gland extract (SGE) and saliva from Dermacentor variabilis have
      distinct effects on platelet-derived growth factor (PDGF)-stimulated IC-21
      macrophage and NIH3T3-L1 fibroblast migration. Since tick saliva contains a high
      concentration of prostaglandin E2 (PGE2), a potent modulator of inflammation, we
      used a PGE2 receptor antagonist to evaluate the role of PGE2 in the different
      migratory responses induced by saliva and its impact on macrophage cytokine
      profile. METHODS: Adult ticks were fed on female New Zealand white rabbits for 5
      8 days. Female ticks were stimulated with dopamine/theophylline to induce
      salivation and saliva was pooled. Competitive enzyme immunoassays (EIA) were used
      to measure saliva PGE2 content and the changes in macrophage intracellular cyclic
      adenosine monophosphate (cAMP) levels. The effects of tick saliva on macrophage
      and fibroblast migration were assessed in the absence and presence of the PGE2
      receptor antagonist, AH 6809, using blind well chamber assays. A cytokine
      antibody array was used to examine the effects of tick saliva on macrophage
      cytokine secretion. Statistical significance was determined by one-way ANOVA;
      Student Newman-Kuels post-test was used for multiple comparisons. RESULTS: The
      saliva-induced increase in PDGF-stimulated macrophage migration was reversed by
      AH 6809. The inhibition of PDGF-stimulated fibroblast migration by saliva was
      also antagonist-sensitive. Tick saliva induced macrophages to secrete copious
      amounts of PGE2, and conditioned medium from these cells caused an AH 6809
      sensitive inhibition of stimulated fibroblast migration, showing that macrophages
      can regulate fibroblast activity. We show that tick saliva decreased the
      secretion of the pro-inflammatory cytokines regulated and normal T cell expressed
      and secreted (RANTES/CCL5), tumor necrosis factor-alpha (TNF-alpha), and soluble
      TNF receptor I (sTNFRI) through a PGE2-dependent mechanism mediated by cAMP.
      Saliva had similar effects on lipopolysaccharide (LPS) stimulated macrophages.
      CONCLUSIONS: Our data show that ticks utilize salivary PGE2 to subvert the
      ability of macrophages to secrete pro-inflammatory mediators and recruit
      fibroblasts to the feeding lesion, therefore inhibiting wound healing.

PMID- 24025200
TI  - Through the eye of the needle: recent advances in understanding biopolymer
      translocation.
AB  - In recent years polymer translocation, i.e., transport of polymeric molecules
      through nanometer-sized pores and channels embedded in membranes, has witnessed
      strong advances. It is now possible to observe single-molecule polymer dynamics
      during the motion through channels with unprecedented spatial and temporal
      resolution. These striking experimental studies have stimulated many theoretical
      developments. In this short theory-experiment review, we discuss recent progress
      in this field with a strong focus on non-equilibrium aspects of polymer dynamics
      during the translocation process. 

PMID- 24025201
TI  - Fabrication of unique chemical patterns and concentration gradients with visible
      light.
AB  - A modular and general method based on a photomediated ATRA reaction for the
      spatially controlled functionalization of surfaces with visible light is
      reported. The ability to control reactivity with light intensity combined with
      the orthogonality of ATRA chemistry allows well-defined chemically differentiated
      monolayers and complex nonlinear chemical concentration gradients to be easily
      prepared. Use of light to mediate these reactions permits spatial regulation and
      the generation of unique, multifunctional chemical gradients. 

PMID- 24025202
TI  - [Basic technology of LC-MS/MS analysis in food safety].

PMID- 24025203
TI  - [Residual pesticide concentrations after processing various types of tea and tea
      infusions].
AB  - The effects of processing to produce various types of tea or infusion on the
      levels of pesticide residues in tea were investigated for three insecticides
      (chlorfenapyr, pyrimiphos-methyl, and clothianidin). Tea plants were sprayed with
      one of the three pesticides and cultivated under cover. The levels of pesticide
      residues in tea decreased after processing according to the time and temperature
      of heating, as well as fermentation. Although significant differences were not
      observed among the three pesticides in the ratio of decreased of pesticide
      concentration after processing to green tea, clothianidin, which is a
      neonicotinoid insecticide and has a lower log Pow value, tended to be transferred
      more than the other two insecticides into infusions. However, no significant
      difference in the ratios of clothianidin transferred to infusions was observed
      among green tea with three different leaf sizes. 

PMID- 24025204
TI  - Inter-laboratory study of an LC-MS/MS method for simultaneous determination of
      fumonisin B1, B2 and B3 in corn.
AB  - To validate an LC-MS/MS method using a strong anion exchange cartridge for
      simultaneous determination of fumonisin B1, B2 and B3 in corn, an inter
      laboratory study was performed in 9 laboratories using one fumonisin-negative
      corn sample, three spiked corn samples (FB1: 100-1,000 MUg/kg, FB2 and FB3: 10
      100 MUg/kg) and two naturally contaminated corn samples. The recoveries were in
      the ranges of 79.7-87.2% for FB1, 78.6-103.2% for FB2 and 80.1-92.8% for FB3. The
      relative standard deviations for repeatability (RSDr) ranged from 3.7 to 8.0% for
      FB1, from 2.6 to 15.3% for FB2 and from 4.3 to 9.7% for FB3. The relative
      standard deviations for reproducibility (RSDR) for FB1, FB2 and FB3 were in the
      ranges of 6.3-10.1%, 5.9-18.7% and 9.3-16.0%, respectively. The HorRat values for
      all analytes ranged from 0.2 to 0.9. The difference of the trueness between the
      two kinds of commercially available anion exchange cartridges used in this study
      was not significant (p>0.05). Surveillance for fumonisins in corn grits was
      performed using the validated method. All of the samples were contaminated with
      fumonisins and the mean concentrations for FB1, FB2 and FB3 were 118.1, 37.3 and
      17.9 MUg/kg, respectively. These results indicated that the method for
      simultaneous determination of FB1, FB2 and FB3 in corn was successfully developed
      and validated. 

PMID- 24025205
TI  - [Distribution of toxicity in liver of wild pufferfish Takifugu rubripes].
AB  - Livers from wild pufferfish, Takifugu rubripes, can be described as having a
      smooth frontal side and an upper-region that is attached to the hepatic portal
      vein. Based on this description, the liver can be divided into 10 parts (L1-5 and
      R1-5), and in this work, the lethal potency of each part was determined by mouse
      bioassay. Among the raw livers from 58 individuals, all 10 parts of 16
      individuals, and some parts of 4 individuals showed mouse lethality, but no
      toxicity was detected in any part of the liver from 22 individuals. In the livers
      of 4 individuals that were partially toxic, the lethal potency of the toxic parts
      was less than 4 mouse units (MU)/g, and no part showed especially high toxicity.
      The remaining 16 individuals were considered non-toxic based on the assay of only
      one part. Among 13 frozen livers, all parts of 9 individuals were toxic, while
      all parts of 4 individuals were non-toxic. Liquid chromatography-mass
      spectrometry analysis revealed that all parts of a weakly toxic raw liver and a
      strongly toxic frozen liver had tetrodotoxin as the major toxin. Regarding the 16
      raw and 9 frozen livers, whose parts were all toxic, the relative lethal potency
      of each part to the mean lethal potency of the individual (8.9-709 MU/g) was
      calculated, and subjected to a two-way analysis of variance with 2 factors
      (left/right and top/bottom) for each group of livers (raw or frozen). The
      analysis indicated non-significance among factors and interactions at a
      significance level of 5% in the frozen livers. However, in the raw livers,
      although no interaction between the 2 factors was detected, the right-side and
      the 4th-portion from the top were significantly higher than the left-side and the
      other portions, respectively. Therefore, we concluded that individual inspection
      using R4, which is the region that lies below the right-center location of the
      liver, is suitable for toxicity evaluation of liver to ensure the safe
      consumption of pufferfish. 

PMID- 24025206
TI  - [Information sources for causality assessment of health problems related to
      health foods and their usefulness].
AB  - Collecting adverse case reports suspected to be due to health foods and
      evaluation of the causality are important to secure safety, even if the causal
      relationship between health foods and reported health problem is uncertain. Case
      reports are mainly collected at three sites: public health centers, practical
      living information online network system(PIO-NET), and individual companies. The
      case reports from the three sources are not dealt with consistently. In this
      study, we investigated and characterized those case reports from the viewpoint of
      evaluating causality, using the causality association rating methods, namely, the
      dendritic and pointed methods, which we reported previously. Information in
      public health centers comprised 20 reports per year; approximately 40% were from
      health care providers and contained detailed medical data. PIO-NET information
      comprised 366 reports per year; 80% were self-reports from users, and few medical
      details were included. Company information covered 1,323 cases from 13 companies;
      more than 90% were from users and most of them were complaints. Case reports from
      public health centers and PIO-NET showed that the largerst number of victims were
      female aged >60, with allergy and gastrointestinal symptoms. When these case
      reports from the letter two sources were examined using the causality association
      rating systems, most were rated as "possible" and only a few were rated as
      "probable". As specific case reports from different information sources were
      examined in this study, we were able to identify several points that should be
      improved in our two rating methods. However, to ensure the safety of health
      foods, it will be necessary to collect a large number of high-quality case
      reports for evaluation by a suitable causality rating method, and to integrate
      those evaluated case reports into a single site. 

PMID- 24025207
TI  - [Simultaneous determination of veterinary drugs in livestock products using
      dispersive and cartridge column solid-phase extraction by LC-MS/MS].
AB  - A method using dispersive and cartridge column solid-phase extraction (SPE) was
      developed for the simultaneous determination of veterinary drugs in livestock
      products by LC-MS/MS. The samples were extracted with 85% acetonitrile and
      cleaned up using dispersive and cartridge column SPE. Recoveries of 70 analytes
      fortified at the levels of 0.002 MUg/g and 0.01 MUg/g in cattle, swine and
      chicken muscles were examined. Among 70 analytes examined, 64 in cattle, 58 in
      swine and 49 in chicken satisfied the required Japanese validation guideline. The
      limit of quantitation values of the 70 analytes were 0.001 MUg/g or 0.005 MUg/g
      in three kinds of livestock products. This method is suitable to analyze 40
      analytes in three kinds of livestock products at levels under the MRL. 

PMID- 24025208
TI  - [Reduction of radioactive cesium content in beef by soaking in seasoning].
AB  - It is important to obtain information about ways of removing radioactive cesium
      from foods in order to reduce internal radiation exposure from food and to ensure
      the safety and security of food. In this study, we investigated the change of
      radioactive cesium content in beef due to soaking in seasoning. Our results
      revealed that soaking beef in liquid seasoning (salt concentration: 8-10%) for 24
      h or in miso seasoning (salt concentration: about 9%) for 7 days decreased the
      radioactive cesium content by about 20% and 55%, respectively, compared with that
      present in beef before soaking. Furthermore, soaking beef in 10% salt solution
      for 7 days while changing the salt solution every day or every three days
      decreased the radioactive cesium content by about 75%, compared with that present
      in beef before soaking. Because the seasoning is usually discarded after soaking,
      the procedure of soaking beef in seasoning is a useful method of reducing the
      burden of radioactive cesium. 

PMID- 24025209
TI  - [Reduction of radioactive cesium content in pond smelt by cooking].
AB  - In Japan, seafood may be eaten raw or after having been cooked in diverse ways.
      Therefore, it is important to understand the effect of cooking on the extent of
      contamination with radioactive materials in order to avoid internal exposure to
      radioactive materials via seafood. In this study, we investigated the changes in
      radioactive cesium content in pond smelt cooked in four different ways: grilled,
      stewed (kanroni), fried and soaked (nanbanzuke). The radioactive cesium content
      in grilled, kanroni and fried pond smelt was almost unchanged compared with the
      uncooked state. In contrast, radioactive cesium content in nanbanzuke pond smelt
      was decreased by about 30%. Our result suggests that soaking cooked pond smelt in
      seasoning is an effective method of reducing the burden radioactive cesium. 

PMID- 24025210
TI  - Comparison of DNA extraction methods for sweet corn and processed sweet corns.
AB  - DNA was extracted from sweet corn and its processed products using four DNA
      extraction methods: the CTAB method, the DNeasy Plant Maxi kit, GM Quicker 3, and
      Genomic-tip 20/G. DNA was successfully extracted from raw sweet corn and baby
      corn samples using all four methods. Meanwhile, from frozen, canned, and dry pack
      products, DNA was well extracted using the DNeasy Plant Maxi kit, GM Quicker 3,
      and Genomic-tip 20/G, but not enough with the CTAB method. The highest yield of
      DNA was obtained with Genomic-tip 20/G. The degree of degradation of extracted
      DNA was observed to increase in the order of raw, frozen, canned, dry pack, and
      baby corn samples. To evaluate the quality of extracted DNA, real-time PCR
      analyses were conducted using three maize endogenous genes. The DNAs extracted
      using GM Quicker 3 had high purity, suggesting that GM Quicker 3 would be the
      most suitable method for DNA extraction from processed sweet corn products. 

PMID- 24025211
TI  - [Survey of pesticide residues in imported spices and herbs (1997.4-2011.3)].
AB  - A survey of pesticide residues in 313 samples of imported spices and herbs on the
      Tokyo market from April 1997 to March 2011 was carried out. Thirty-seven kinds of
      pesticides, including organophosphorus, organochlorine, pyrethroid, carbamate and
      others, were detected between levels of trace (below 0.01 ppm) and 3.3 ppm from
      64 samples. The rate of detection was highest in peel (100%) followed by stem
      (66.7%), fruit (34.5%), bark (33.3%), flower (31.3%) and leaf (14.7%). No
      residues were detected in root, seed or whole grass. Organochlorine pesticides
      were detected in all plant parts. The insecticides were detected in products from
      all production areas, suggesting that their use is common. Residue levels of
      these pesticides were calculated as less than 1% of their ADI values, based on
      the daily intake of spices and herbs. Therefore, these spices and herbs should be
      safe when consumed in customary amounts. 

PMID- 24025212
TI  - [Study of long-term water quality of stocked drinking water].
AB  - We examined changes in the quality of drinking water stockpiled under various
      conditions for emergency use. The results indicated that the change in the
      quality of the stocked water was influenced mainly by the preservation period and
      not by the amount of water in the bottle. To maintain water quality, the amount
      of residual chlorine is less important than using sufficiently sterilized water,
      bottles and caps in the bottling process. Washing the bottles with a small amount
      of boiling water was not sufficient to ensure complete inhibition of microbial
      growth. 

PMID- 24025213
TI  - [Basic principles for setting acute reference dose, ARfD in Japan].
AB  - Basic principles for simulation of acute reference dose (ARfD) setting were
      defined based on the work of Solecki et al. (2005). The principles are: (1)
      Appearance of acute toxicity within 24 h after oral administration. (2) Rationale
      for setting toxicity that appears or could appear after single oral
      administration. (3) ARfD setting is assumed to be necessary for all pesticides.
      (4) ARfD setting is not necessary when the value is at or above the cutoff level.
      (5) The setting basically applies to the general population. (6) ARfD is set
      based on the lowest NOAEL among all the available study data concerning endpoints
      for acute effects. (7) Effects of exposure during critical periods should be
      considered as endpoints for ARfD setting. (8) The approach for the safety
      coefficient is the same as that for acceptable daily intake. (9) If available,
      human data are acceptable as an endpoint for ARfD setting. 

PMID- 24025214
TI  - Single-laboratory validation study of rapid analysis method for multi-class
      veterinary drugs in milk, fish and shellfish by LC-MS/MS.
AB  - A method of rapid analysis of multi-class residual veterinary drugs in milk, fish
      and shellfish was validated in accordance with Japanese guidelines for the
      validation of analytical methods for residual agricultural chemicals in food.
      Using LC-MS/MS, 43 multi-class veterinary drugs, including sulfonamides,
      quinolones, coccidiostats and antiparasites, could be analyzed in one injection.
      Analytes were extracted from samples with two kinds of solvent, acetonitrile
      containing 1 vol% formic acid and anhydrous acetonitrile, and salted out with 4.0
      g of magnesium sulfate, 1.5 g of trisodium citrate and 2.0 g of sodium chloride.
      This method was assessed by performing recovery tests in retail milk and 4 kinds
      of fresh cultured fish and shellfish (salmon, tiger shrimp, red sea bream and
      bastard halibut) spiked with the 43 target analytes at the levels of 10 and 100
      MUg/kg. Using this method, 40 out of 43 drugs satisfied the guideline criteria in
      milk, 37 drugs in salmon, 42 drugs in tiger shrimp, 41 drugs in red sea bream and
      39 drugs in bastard halibut. 

PMID- 24025215
TI  - [Evaluation of an analytical method for cyanogenic compounds in bean paste and
      its application for surveillance of real samples].
AB  - In order to ensure compliance of raw bean paste products with the Japanese Food
      Sanitation Law, we examined the performance characteristics of an analytic
      procedure based on steam distillation followed by carbonate-pyrazolone assay to
      determine cyanogenic compounds in raw bean paste. The present method includes a
      procedure for decomposition cyanogenic glycosides using linamarase due to the
      possibility that cyanogenic glycoside-hydrolyzing enzymes might be deactivated in
      raw bean pastes. The performance of the method was evaluated using two types of
      bean paste spiked with a cyanogenic glycoside (linamarin) corresponding to
      cyanide ion concentrations of 5 and 10 mg/kg. The trueness of the method was 86
      90%, and the repeatability (RSD) was 1.0-2.4%, while the intermediate precision
      (RSD) was 2.6% to 4.9%. A surveillance of cyanogenic compounds in 28 raw bean
      pastes manufactured in Japan was then carried out with the validated method. One
      sample contained 15 mg/kg (as hydrogen cyanide), while the other samples
      contained less than 5 mg/kg. 

PMID- 24025217
TI  - Coherent topological defect dynamics and collective modes in superconductors and
      electronic crystals.
AB  - The control of condensed matter systems out of equilibrium by laser pulses allows
      us to investigate the system trajectories through symmetry-breaking phase
      transitions. Thus the evolution of both collective modes and single-particle
      excitations can be followed through diverse phase transitions with femtosecond
      resolution. Here we present experimental observations of the order parameter
      trajectory in the normal -> superconductor transition and charge density wave
      ordering transitions. Of particular interest is the coherent evolution of
      topological defects forming during the transition via the Kibble-Zurek mechanism,
      which appears to be measurable in optical pump-probe experiments. Experiments on
      CDW systems reveal some new phenomena, such as coherent oscillations of the order
      parameter, the creation and emission of dispersive amplitude modes upon the
      annihilation of topological defects, and mixing with weakly coupled finite
      frequency (massive) bosons. 

PMID- 24025216
TI  - Carbon nanotubes as a novel tool for vaccination against infectious diseases and
      cancer.
AB  - Due to their unusual properties, carbon nanotubes have been extensively employed
      in electronics, nanotechnology and optics, amongst other. More recently, they
      have also been used as vehicles for drug and antigen delivery, the latter being a
      novel immunization strategy against infectious diseases and cancer. Here we
      discuss the potential of carbon nanotubes as an antigen delivery tool and suggest
      further directions in the field of vaccination. 

PMID- 24025219
TI  - Early stress evokes temporally distinct consequences on the hippocampal
      transcriptome, anxiety and cognitive behaviour.
AB  - The early stress of maternal separation (ES) exerts long-lasting effects on
      cognition and anxiety. Recent evidence indicates enhanced hippocampus-dependent
      spatial learning in young adult ES animals, which shifts towards a decline in
      long-term memory in middle-aged life. Further, we find that ES animals exhibit
      enhanced anxiety in young adulthood that does not persist into middle-aged life.
      Here, we demonstrate unique, predominantly non-overlapping, hippocampal
      transcriptomes in young adult and middle-aged ES animals that accompany the
      temporally-specific behavioural consequences. Strikingly, the extent of gene
      dysregulation in middle-aged ES animals was substantially higher than in young
      adulthood. Functional analysis revealed distinct biological processes enriched at
      the two ages, highlighting the temporal shift in ES-evoked gene regulation. Our
      results suggest that ES history interacts with aging to exacerbate age-associated
      transcriptional changes and cognitive decline. qPCR profiling of histone
      deacetylases (Hdacs) and histone methyltransferases (HMTs) revealed an age
      dependent, opposing regulation with decreased expression noted in young adult ES
      animals (Hdac 2, 7, 8, 9 and Suv39h1) and enhanced levels in middle-aged life
      (Hdac 2, 6, 8 and Suv39h1). While altered expression of histone modifying enzymes
      did not translate into global histone acetylation or methylation changes, we
      noted differential enrichment of histone acetylation and methylation
      modifications at the promoters of multiple genes regulated in the hippocampi of
      young adult and middle-aged ES animals. Our results highlight the differential
      molecular and behavioural consequences of ES across a life-span, and suggest a
      possible role for epigenetic mechanisms in contributing to the temporally
      specific transcriptional changes following ES. 

PMID- 24025218
TI  - Alleviation of chronic neuropathic pain by environmental enrichment in mice well
      after the establishment of chronic pain.
AB  - BACKGROUND: In animal models, the impact of social and environmental
      manipulations on chronic pain have been investigated in short term studies where
      enrichment was implemented prior to or concurrently with the injury. The focus of
      this study was to evaluate the impact of environmental enrichment or
      impoverishment in mice three months after induction of chronic neuropathic pain.
      METHODS: Thirty-four CD-1 seven to eight week-old male mice were used. Mice
      underwent surgery on the left leg under isoflurane anesthesia to induce the
      spared nerve injury model of neuropathic pain or sham condition. Mice were then
      randomly assigned to one of four groups: nerve injury with enriched environment
      (n = 9), nerve injury with impoverished environment (n = 8), sham surgery with
      enriched environment (n = 9), or sham surgery with impoverished environment (n =
      8). The effects of environmental manipulations on mechanical (von Frey filaments)
      heat (hot plate) and cold (acetone test) cutaneous hypersensitivities, motor
      impairment (Rotarod), spontaneous exploratory behavior (open field test), anxiety
      like behavior (elevated plus maze) and depression-like phenotype (tail suspension
      test) were assessed in neuropathic and control mice 1 and 2 months post
      environmental change. Finally, the effect of the environment on spinal expression
      of the pro-nociceptive neuropeptides substance P and CGRP form the lumbar spinal
      cord collected at the end of the study was evaluated by tandem liquid
      chromatography mass spectrometry. RESULTS: Environmental enrichment attenuated
      nerve injury-induced hypersensitivity to mechanical and cold stimuli. In
      contrast, an impoverished environment exacerbated mechanical hypersensitivity. No
      antidepressant effects of enrichment were observed in animals with chronic
      neuropathic pain. Finally, environmental enrichment resulted lower SP and CGRP
      concentrations in neuropathic animals compared to impoverishment. These effects
      were all observed in animals that had been neuropathic for several months prior
      to intervention. CONCLUSIONS: These results suggest that environmental factors
      could play an important role in the rehabilitation of chronic pain patients well
      after the establishment of chronic pain. Enrichment is a potentially inexpensive,
      safe and easily implemented non-pharmacological intervention for the treatment of
      chronic pain.

PMID- 24025221
TI  - The effect of psychoeducation on the functioning level of patients with bipolar
      disorder.
AB  - Bipolar disorder has adverse effects on the lives of the individuals and the
      people around them and causes disability due to impaired social and occupational
      functioning, risk of suicide, and frequent relapses. This study was conducted as
      a two-group pretest-posttest design to determine the effect of psychoeducation on
      the functioning levels of patients with bipolar disorder. A total of 80 patients
      were assigned to either the experimental (n = 40) or the control group (n = 40).
      The data were collected using a questionnaire form, and the Bipolar Disorder
      Functioning Questionnaire. The experimental group scored significantly higher on
      the functioning levels (emotional functioning, intellectual functioning, feelings
      of stigmatization, social withdrawal, household relations, relations with
      friends, participating in social activities, daily activities and recreational
      activities, taking initiative and self-sufficiency, and occupation) (p < .05)
      compared with the control group after psychoeducation. Psychoeducation has become
      considerably effective in increasing the functioning levels of patients with
      bipolar disorder. 

PMID- 24025220
TI  - A sero-survey of toxoplasmosis in farm and non-farm children from Wisconsin,
      United States, 1997-1999.
AB  - BACKGROUND: Toxoplasmosis is among the most widespread and prevalent zoonosis in
      the world. People can become infected through ingestion of oocysts shed by felids
      or of tissue cysts contained in meat from infected animals. Acute infection can
      result in a wide spectrum of consequences, including flu-like illness and
      retinitis, as well as congenital infection in pregnant women. Severe disease can
      occur, especially if people are immunocompromised. Frequency of human infection
      varies substantially by region due to ecological, social, and cultural factors.
      The most recent nationwide prevalence estimates in children from United States
      were 3.6% in 6-11 year olds and 5.8% in 12-19 year olds. Because of the limited
      knowledge of the occurrence of common zoonotic pathogens in children in the
      United States, the objective of this study was to estimate the sero-prevalence of
      T. gondii-specific antibodies in children from the Marshfield area in Wisconsin
      and to examine the association between sero-positivity and farm living. METHODS:
      Banked sera from 342 Wisconsin children collected in 1997-1999, aged 2 to 18
      years, were tested for Toxoplasma gondii-specific IgG antibodies using ELISA.
      Recorded information included age, sex, and whether the child resided on a farm.
      Impact of assay accuracy, sensitivity and specificity, on sero-prevalence was
      examined using Bayesian methods. RESULTS: Observed prevalence of T. gondii
      specific antibodies was 10.8% (37/347). Adjusting for sensitivity and specificity
      of the assays yielded a prevalence estimate of 8.0% (95% probability interval: 4%
      12.4%). Children living on a farm had a 5 times higher odds of T. gondii-specific
      antibodies than children not living on a farm (OR=5.08, 95% CI: 2.2-11.6).
      CONCLUSION: Results suggest that even in apparently low-risk populations, the
      true extent of the infection in children is significant. In this study
      population, children living on farms were differentially exposed, with earlier
      and higher infection risk than children not living on farms. Findings highlight
      the need to increase awareness about toxoplasmosis acquired early in life and to
      improve our understanding of the ecology of T. gondii in rural environments from
      developed and developing countries.

PMID- 24025222
TI  - Migration and cognitive representations of hypertension in african immigrant
      women.
AB  - The purpose of this study was to use the Self-Regulation Model on African
      immigrant women, to determine the association of migration and residence in the
      United States with cognitive representations and dietary behavior, and also to
      explore migration stress and blood pressure (BP) in them. Participants included a
      convenience sample of 91 Nigerian immigrant women (NIW) and 38 African American
      women (AAW). Data collection instruments were the Acculturative Stress Scale and
      the Women's and Men's Hypertension Experiences and Emerging Lifestyle Survey of
      2008-2009. Descriptive t test and ANOVA statistics were used to analyze study
      variables comparing groups and NIW duration of residency in the United States.
      Knowledge of Hypertension and Cognitive Representation of Hypertension were
      significantly increased in the NIW by years of residency. Migration stress had no
      significant relationship with BP level. A longitudinal study initiated on
      immigrants' arrival in the United States is recommended to understand the
      trajectory of chronic illnesses such as hypertension. 

PMID- 24025223
TI  - Metformin inhibits vascular calcification in female rat aortic smooth muscle
      cells via the AMPK-eNOS-NO pathway.
AB  - Metformin exhibits diverse protective effects against diabetic complications,
      such as bone loss. Here, we investigated the effect of metformin on vascular
      calcification, another type 2 diabetes complication. In female rat aortic smooth
      muscle cells (RASMCs), we observed that metformin significantly alleviated beta
      glycerophosphate-induced Ca deposition and alkaline phosphatase activity,
      corresponding with reduced expression of some specific genes in osteoblast-like
      cells, including Runx2 and bone morphogenetic protein-2, and positive effects on
      alpha-actin expression, a specific marker of smooth muscle cells. Mechanistic
      analysis showed that phosphorylation levels of both AMP-activated protein kinase
      (AMPK) and endothelial nitric oxide synthase (eNOS) were increased with NO
      overproduction. After inhibition of either AMPK or eNOS with the pharmacologic
      inhibitors, compound C or Nomega-Nitro-L-arginine methyl ester, NO production was
      lowered and metformin-meditated vascular protection against beta-glycerophosphate
      induced Ca deposition was removed. Our results support that metformin prevents
      vascular calcification via AMPK-eNOS-NO pathway. 

PMID- 24025224
TI  - Bradykinin B2 receptor in the adrenal medulla of male rats and mice:
      glucocorticoid-dependent increase with immobilization stress.
AB  - Bradykinin, acting via the bradykinin B2 receptor (B2R), is a potent stimulator
      of adrenomedullary catecholamine biosynthesis and release and likely plays an
      important role in the adrenomedullary stress response. However, the effects of
      stress on the expression of this receptor in the adrenal medulla are currently
      unclear. Here, we examined the changes in adrenomedullary B2R gene expression in
      male rats in response to single (1 time) and repeated (6 times) exposure to 2
      hours immobilization stress (IMO). Immediately after 1 or 6 times IMO, B2R mRNA
      levels were increased by 9-fold and 7-fold, respectively, and returned to
      unstressed control levels 3 hours later. This large, but transient, increase in
      mRNA elicited a doubling of protein levels 3 hours after the stress exposure.
      Next, the role of the hypothalamic-pituitary-adrenocortical axis in the stress
      induced upregulation of B2R gene expression was examined. Treatment with
      endogenous (corticosterone) and synthetic (dexamethasone) glucocorticoids dose
      dependently increased B2R mRNA levels in adrenomedullary-derived PC12 cells.
      Furthermore, cortisol supplementation at levels mimicking stress exposure
      elevated B2R mRNA levels in the adrenal medulla of hypophysectomized rats. In
      response to 1 exposure to IMO, the stress-triggered rise in plasma corticosterone
      and adrenomedullary B2R mRNA levels was attenuated in CRH-knockout mice and
      absent in pharmacologically adrenalectomized rats, indicating a requirement for
      glucocorticoids in the upregulation of B2R gene expression with stress. Overall,
      the increase in B2R gene expression in response to the stress-triggered rise in
      glucocorticoids likely enhances catecholamine biosynthesis and release and may
      serve as an adaptive response of the adrenomedullary catecholaminergic system to
      stress. 

PMID- 24025226
TI  - Mullerian inhibiting substance in the caudate amphibian Pleurodeles waltl.
AB  - Mullerian inhibiting substance (MIS, also known as anti-Mullerian hormone), is a
      key factor of male sex differentiation in vertebrates. In amniotes, it is
      responsible for Mullerian duct regression in male embryos. In fish, despite the
      absence of Mullerian ducts, MIS is produced and controls germ cell proliferation
      during gonad differentiation. Here we show for the first time the presence of MIS
      in an amphibian species, Pleurodeles waltl. This is very astonishing because in
      caudate amphibians, Mullerian ducts do not regress in males. Phylogenetic
      analysis of MIS P. waltl ortholog revealed that the deduced protein segregates
      with MIS from other vertebrates and is clearly separated from other TGF-beta
      family members. In larvae, MIS mRNA was expressed at higher levels in the
      developing testes than in the ovaries. In the testis, MIS mRNA expression was
      located within the lobules that contain Sertoli cells. Besides, expression of MIS
      was modified in the case of sex reversal: it increased after masculinizing heat
      treatment and decreased after estradiol feminizing exposure. In addition to the
      data obtained recently in the fish medaka, our results suggest that the role of
      MIS on Mullerian ducts occurred secondarily during the course of evolution. 

PMID- 24025227
TI  - Return of the memento mori: imaging death in public health.

PMID- 24025225
TI  - Differential control of sex differences in estrogen receptor alpha in the bed
      nucleus of the stria terminalis and anteroventral periventricular nucleus.
AB  - The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) and
      anteroventral periventricular nucleus of the hypothalamus (AVPV) are sexually
      dimorphic, hormone-sensitive forebrain regions. Here we report a profound sex
      difference in estrogen receptor-alpha (ERalpha) immunoreactivity (IR) in the
      BNSTp, with robust ERalpha IR in females and the near absence of labeling in
      males. This sex difference is due to the suppression of ERalpha IR by testicular
      hormones in adulthood: it was not present at birth and was not altered by
      neonatal treatment of females with estradiol; gonadectomy of adult males
      increased ERalpha IR to that of females, whereas gonadectomy of adult females had
      no effect. Treating gonadally intact males with an aromatase inhibitor partially
      feminized ERalpha IR in the BNSTp, suggesting that testicular suppression
      required aromatization. By contrast, in AVPV we found a modest sex difference in
      ERalpha IR that was relatively insensitive to steroid manipulations in adulthood.
      ERalpha IR in AVPV was, however, masculinized in females treated with estradiol
      at birth, suggesting that the sex difference is due to organizational effects of
      estrogens. The difference in ERalpha IR in the BNSTp of males and females appears
      to be at least in part due to greater expression of mRNA of the ERalpha gene
      (Esr1) in females. The sex difference in message is smaller than the difference
      in immunoreactivity, however, suggesting that posttranscriptional mechanisms also
      contribute to the pronounced suppression of ERalpha IR and presumably to
      functions mediated by ERalpha in the male BNSTp. 

PMID- 24025228
TI  - Recent pharmacological advances for treating venous thromboembolism: are we
      witnessing the demise of warfarin?
AB  - Vitamin K antagonists, such as warfarin, have been the mainstay in treatment and
      prophylaxis of venous thromboembolism. However, warfarin has many disadvantages
      including a narrow therapeutic window, numerous potential drug interactions,
      modulation of effect by alcohol and foods containing vitamin K and genetic
      variation in metabolism of warfarin, all of which contribute to the
      unpredictability of therapy. This has provided the impetus for developing new
      oral anticoagulants with a rapid onset of action, wide therapeutic window,
      predictable and reversible action, with few drug or dietary interactions, no
      requirement for routine coagulation monitoring or dose adjustment and acceptable
      cost. No single agent incorporates all these characteristics, but new factor Xa
      and direct thrombin inhibitors are being introduced into clinical practice that
      fulfil some of these aims. Here, we briefly discuss the current practice with its
      limitations and pitfalls, and then review important trials that have launched new
      oral anticoagulants into clinical practice. 

PMID- 24025229
TI  - Austere or not? UK coalition government budgets and health inequalities.

PMID- 24025232
TI  - Confusion, knock-down and kill of Aedes aegypti using metofluthrin in domestic
      settings: a powerful tool to prevent dengue transmission?
AB  - BACKGROUND: Dengue control methods are reliant upon control of the vector,
      primarily Aedes aegypti. Current adulticiding methods in North Queensland include
      treating premises with residual synthetic pyrethroid insecticides (interior
      residual spraying; IRS), a laborious, intrusive task. The vapor active synthetic
      pyrethroid metofluthrin might offer an efficient alternative as some studies
      indicate that it prevents biting and has strong knockdown effects. However, its
      expellant and/or irritant effects, longevity, residual activity and the speed
      with which biting behavior is disrupted have not yet been characterized. METHODS:
      We exposed cohorts of Cairns colony (F2-4) Ae. aegypti to rooms (17-24 m3)
      treated with 5% and 10% AI metofluthrin emanators. Using free-flying and caged
      populations we measured biting (human landing rate), expulsion through unscreened
      windows, knockdown and death over periods ranging between a few minutes and 24
      hrs. Observations of the behavior of single female Ae. aegypti exposed to
      metofluthrin were also made. RESULTS: Female Ae. aegypti exposed to 5% or 10%
      metofluthrin formulations were almost entirely inhibited from biting. This was
      the result of rapid knockdown and mortality (80-90% in less than one hour) and to
      the behavioral impacts of exposure that, within minutes, caused female Ae.
      aegypti to become disoriented, stop landing on hosts, and seek resting sites.
      Exposed mosquitoes did not exhibit any increased propensity to exit treated rooms
      and the 10% AI resin remained fully active for at least 20 days. CONCLUSION: The
      new, high-dose, resin formulations of metofluthrin act quickly to prevent biting
      and to knockdown and kill free-flying female Ae. aegypti in our experimental
      rooms. There was no evidence that metofluthrin induced escape from treated areas.
      Resin-based metofluthrin emanators show great potential as a replacement for
      labor intensive IRS for dengue vector control.

PMID- 24025235
TI  - Efficient heterogeneous catalytic hydrogenation of acetone to isopropanol on
      semihollow and porous palladium nanocatalyst.
AB  - Highly efficient and remarkable selective acetone conversion to isopropanol has
      been achieved via a heterogeneous catalytic hydrogenation of acetone by NaBH4 in
      the presence of semihollow palladium nanoparticles (PdNPs) grown on ITO
      substrate. PdNPs with high surface defect grown on an indium tin oxide (ITO)
      surface were prepared via a simple immersion of the substrate into a solution
      containing K2PdCl6, sodium dodecyl sulphate (SDS), and formic acid for 2 h at
      room temperature. The sample showed remarkably high heterogeneous catalytic
      efficiency by producing 99.8% of isopropanol within 6 min using only 0.28 MUg of
      PdNPs on the ITO surface. The present system exhibits heterogenenous catalytic
      hydrogenation efficiency 1 * 10(6) time higher than using the conventional Raney
      Ni system. 

PMID- 24025234
TI  - Feasibility study on full closed-loop control ventilation (IntelliVent-ASVTM) in
      ICU patients with acute respiratory failure: a prospective observational
      comparative study.
AB  - INTRODUCTION: IntelliVent-ASVTM is a full closed-loop ventilation mode that
      automatically adjusts ventilation and oxygenation parameters in both passive and
      active patients. This feasibility study compared oxygenation and ventilation
      settings automatically selected by IntelliVent-ASVTM among three predefined lung
      conditions (normal lung, acute respiratory distress syndrome (ARDS) and chronic
      obstructive pulmonary disease (COPD)) in active and passive patients. The
      feasibility of IntelliVent-ASVTM use was assessed based on the number of safety
      events, the need to switch to conventional mode for any medical reason, and
      sensor failure. METHOD: This prospective observational comparative study included
      100 consecutive patients who were invasively ventilated for less than 24 hours at
      the time of inclusion with an expected duration of ventilation of more than 12
      hours. Patients were ventilated using IntelliVent-ASVTM from inclusion to
      extubation. Settings, automatically selected by the ventilator, delivered
      ventilation, respiratory mechanics, and gas exchanges were recorded once a day.
      RESULTS: Regarding feasibility, all patients were ventilated using IntelliVent
      ASVTM (392 days in total). No safety issues occurred and there was never a need
      to switch to an alternative ventilation mode. The fully automated ventilation was
      used for 95% of the total ventilation time. IntelliVent-ASVTM selected different
      settings according to lung condition in passive and active patients. In passive
      patients, tidal volume (VT), predicted body weight (PBW) was significantly
      different between normal lung (n = 45), ARDS (n = 16) and COPD patients (n = 19)
      (8.1 (7.3 to 8.9) mL/kg; 7.5 (6.9 to 7.9) mL/kg; 9.9 (8.3 to 11.1) mL/kg,
      respectively; P 0.05). In passive ARDS patients, FiO2 and positive end-expiratory
      pressure (PEEP) were statistically higher than passive normal lung (35 (33 to
      47)% versus 30 (30 to 31)% and 11 (8 to 13) cmH2O versus 5 (5 to 6) cmH2O,
      respectively; P< 0.05). CONCLUSIONS: IntelliVent-ASVTM was safely used in
      unselected ventilated ICU patients with different lung conditions. Automatically
      selected oxygenation and ventilation settings were different according to the
      lung condition, especially in passive patients. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT01489085.

PMID- 24025236
TI  - Development and Alpha Testing of QuitIT: An Interactive Video Game to Enhance
      Skills for Coping With Smoking Urges.
AB  - BACKGROUND: Despite many efforts at developing relapse prevention interventions,
      most smokers relapse to tobacco use within a few months after quitting.
      Interactive games offer a novel strategy for helping people develop the skills
      required for successful tobacco cessation. OBJECTIVE: The objective of our study
      was to develop a video game that enables smokers to practice strategies for
      coping with smoking urges and maintaining smoking abstinence. Our team of game
      designers and clinical psychologists are creating a video game that integrates
      the principles of smoking behavior change and relapse prevention. We have
      reported the results of expert and end-user feedback on an alpha version of the
      game. METHODS: The alpha version of the game consisted of a smoking cue scenario
      often encountered by smokers. We recruited 5 experts in tobacco cessation
      research and 20 current and former smokers, who each played through the scenario.
      Mixed methods were used to gather feedback on the relevance of cessation content
      and usability of the game modality. RESULTS: End-users rated the interface from
      3.0 to 4.6/5 in terms of ease of use and from 2.9 to 4.1/5 in terms of
      helpfulness of cessation content. Qualitative themes showed several user
      suggestions for improving the user interface, pacing, and diversity of the game
      characters. In addition, the users confirmed a high degree of game immersion,
      identification with the characters and situations, and appreciation for the
      multiple opportunities to practice coping strategies. CONCLUSIONS: This study
      highlights the procedures for translating behavioral principles into a game
      dynamic and shows that our prototype has a strong potential for engaging smokers.
      A video game modality exemplifies problem-based learning strategies for tobacco
      cessation and is an innovative step in behavioral management of tobacco use.

PMID- 24025237
TI  - Clapeyron slope reversal in the melting curve of AuGa2 at 5.5 GPa.
AB  - We use x-ray diffraction in a resistively heated diamond anvil cell to extend the
      melting curve of AuGa2 beyond its minimum at 5.5 GPa and 720 K, and to constrain
      the high-temperature phase boundaries between cubic (fluorite structure),
      orthorhombic (cottunite structure) and monoclinic phases. We document a large
      change in Clapeyron slope that coincides with the transitions from cubic to lower
      symmetry phases, showing that a structural transition is the direct cause of the
      change in slope. In addition, moderate (~30 K) to large (90 K) hysteresis is
      detected between melting and freezing, from which we infer that at high
      pressures, AuGa2 crystals can remain in a metastable state at more than 5% above
      the thermodynamic melting temperature.

PMID- 24025238
TI  - Gaussianity revisited: exploring the Kibble-Zurek mechanism with superconducting
      rings.
AB  - In this paper we use spontaneous flux production in annular superconductors to
      shed light on the Kibble-Zurek (KZ) scenario. In particular, we examine the
      effects of finite size and external fields, neither of which is directly amenable
      to the KZ analysis. Supported by 1D and 3D simulations, the properties of a
      superconducting ring are seen to be well represented by analytic Gaussian
      approximations which encode the KZ scales indirectly. Experimental results for
      annuli in the presence of external fields corroborate these findings. 

PMID- 24025240
TI  - A black belt in martial arts.

PMID- 24025239
TI  - Pipecolic acid enhances resistance to bacterial infection and primes salicylic
      acid and nicotine accumulation in tobacco.
AB  - Distinct amino acid metabolic pathways constitute integral parts of the plant
      immune system. We have recently identified pipecolic acid (Pip), a lysine-derived
      non-protein amino acid, as a critical regulator of systemic acquired resistance
      (SAR) and basal immunity to bacterial infection in Arabidopsis thaliana. In
      Arabidopsis, Pip acts as an endogenous mediator of defense amplification and
      priming. For instance, Pip conditions plants for effective biosynthesis of the
      phenolic defense signal salicylic acid (SA), accumulation of the phytoalexin
      camalexin, and expression of defense-related genes. Here, we show that tobacco
      plants respond to leaf infection by the compatible bacterial pathogen Pseudomonas
      syringae pv tabaci (Pstb) with a significant accumulation of several amino acids,
      including Lys, branched-chain, aromatic, and amide group amino acids. Moreover,
      Pstb strongly triggers, alongside the biosynthesis of SA and increases in the
      defensive alkaloid nicotine, the production of the Lys catabolites Pip and alpha
      aminoadipic acid. Exogenous application of Pip to tobacco plants provides
      significant protection to infection by adapted Pstb or by non-adapted,
      hypersensitive cell death-inducing P. syringae pv maculicola. Pip thereby primes
      tobacco for rapid and strong accumulation of SA and nicotine following bacterial
      infection. Thus, our study indicates that the role of Pip as an amplifier of
      immune responses is conserved between members of the rosid and asterid groups of
      eudicot plants and suggests a broad practical applicability for Pip as a natural
      enhancer of plant disease resistance. 

PMID- 24025242
TI  - Ecology, genetics, and evolution of body color variations.

PMID- 24025243
TI  - The diversity of male nuptial coloration leads to species diversity in Lake
      Victoria cichlids.
AB  - The amazing coloration shown by diverse cichlid fish not only fascinates aquarium
      keepers, but also receives great attention from biologists interested in
      speciation because of its recently-revealed role in their adaptive radiation in
      an African lake. We review the important role of coloration in the speciation and
      adaptive evolution of Lake Victoria cichlids, which have experienced adaptive
      radiation during a very short evolutionary period. Mature male cichlids display
      their colors during mate choice. The color of their skin reflects light, and the
      reflected light forms a color signal that is received by the visual system of
      females. The adaptive divergence of visual perceptions shapes and diverges
      colorations, to match the adapted visual perceptions. The divergence of visual
      perception and coloration indicates that the divergence of color signals causes
      reproductive isolation between species, and this process leads to speciation.
      Differences in color signals among coexisting species act to maintain
      reproductive isolation by preventing hybridization. Thus, the diversity of
      coloration has caused speciation and has maintained species diversity in Lake
      Victoria cichlids. 

PMID- 24025241
TI  - Intrusive thoughts and quality of life among men with prostate cancer before and
      three months after surgery.
AB  - BACKGROUND: Sudden, unwelcome and repetitive thoughts about a traumatic event-
      intrusive thoughts--could relate to how men assess their quality of life after
      prostate-cancer diagnosis. We aimed to study the prevalence of intrusive thoughts
      about prostate cancer and their association with quality-of-life outcomes before
      and after radical prostatectomy. METHODS: During the first year of the LAPPRO
      trial, 971 men scheduled for radical prostatectomy were prospectively included
      from 14 urological centers in Sweden. Of those, 833 men responded to two
      consecutive study-specific questionnaires before and three months after surgery
      (participation rate 86%). The association of intrusive thoughts with three
      quality-of-life outcomes, i.e. self-assessed quality of life, depressive mood and
      waking up with anxiety was estimated by prevalence ratios that were calculated,
      together with a 95% confidence interval, at the same time-point as well as over
      time. Fisher's exact-test was used to analyze differences between respondents and
      non-respondents. Wilcoxon signed-ranks and Cochran-Armitage trend tests were used
      for analysis of change over time. To validate new questions on intrusive
      thoughts, written answers to open-ended questions were read and analyzed by
      qualitative content analysis. RESULTS: Before surgery, 603 men (73%) reported
      negative intrusive thoughts about their cancer at some time in the past month and
      593 men (59%) reported such thoughts three months after surgery. Comparing those
      reporting intrusive thoughts at least weekly or once a week before surgery with
      those who did not, the prevalence ratio (95% confidence interval), three months
      after surgery, for waking up in the middle of the night with anxiety was 3.9 (2.7
      to 5.5), for depressed mood 1.8 (1.6 to 2.1) and for impaired self-assessed
      quality of life 1.3 (1.2 to 1.5). CONCLUSION: The prevalence of negative
      intrusive thoughts about prostate cancer at the time of surgery associates with
      studied quality-of-life outcomes three months later. TRIAL REGISTRATION: Current
      Controlled Trials, ISRCTN06393679.

PMID- 24025244
TI  - Evolutionary and phylogeographic views on Mc1r and Asip variation in mammals.
AB  - The purpose of this article is to provide basic knowledge about the Mc1r-Asip
      system that promotes the evolution of coat color in mammals, and to stimulate
      genetic, ecological, and phylogeographic studies focusing on color variation in
      natural populations. The topics reviewed herein include: the genetic system of
      the Mc1r and Asip genes related to phenotypic variation; the evolutionary
      implications of the genetic features recorded in their nucleotide sequences; and
      the validity of surveys in the wild of genetic variations in coat color, which
      would facilitate a better understanding of the genetic system, ecological
      meaning, natural history, and taxonomic reevaluation of species and local
      populations. 

PMID- 24025245
TI  - Pigmentation and behavior: potential association through pleiotropic genes in
      Drosophila.
AB  - The molecular basis of pigmentation variation within and among Drosophila species
      is largely attributed to genes in melanin biosynthesis pathway, which involves
      dopamine metabolism. Most of the genetic changes underlying pigmentation
      variations reported to date are changes at the expression levels of the
      structural genes in the pathway. Within D. melanogaster, changes in cis
      regulatory regions of a gene, ebony, are responsible for the naturally occurring
      variation of the body pigmentation intensity. This gene is also known to be
      expressed in glia, and many visual and behavioral abnormalities of its mutants
      have been reported. This implies that the gene has pleiotropic functions in the
      nervous systems. In this review, current knowledge on pigmentation variation and
      melanin biosynthesis pathway are summarized, with some focus on pleiotropic
      features of ebony and other genes in the pathway. A potential association between
      pigmentation and behavior through such pleiotropic genes is discussed in light of
      cis-regulatory structure and pleiotropic mutations. 

PMID- 24025246
TI  - Escherichia coli pyruvate:flavodoxin oxidoreductase, YdbK - regulation of
      expression and biological roles in protection against oxidative stress.
AB  - E. coli YdbK is predicted to be a pyruvate:flavodoxin oxidoreductase (PFOR).
      However, enzymatic activity and the regulation of gene expression of it are not
      well understood. In this study, we found that E. coli cells overexpressing the
      ydbK gene had enhanced PFOR activity, indicating the product of ydbK to be a
      PFOR. The PFOR was labile to oxygen. The expression of ydbK was induced by
      superoxide generators such as methyl viologen (MV) in a SoxS-dependent manner
      after a lag period. We identified a critical element upstream of ydbK gene
      required for the induction by MV and proved direct binding of SoxS to the
      element. E. coli ydbK mutant was highly sensitive to MV, which was enhanced by
      additional inactivation of fpr gene encoding ferredoxin (flavodoxin):NADP(H)
      reductase (FPR). Aconitase activity, a superoxide sensor, was more extensively
      decreased by MV in the E. coli ydbK mutant than in wild-type strain. The
      induction level of soxS gene was higher in E. coli ydbK fpr double mutant than in
      wild-type strain. These results indicate that YdbK helps to protect cells from
      oxidative stress. It is possible that YdbK maintains the cellular redox state
      together with FPR and is involved in the reduction of oxidized proteins including
      SoxR in the late stages of the oxidative stress response in E. coli. 

PMID- 24025247
TI  - Effect of high-LET Fe-ion beam irradiation on mutation induction in Arabidopsis
      thaliana.
AB  - Heavy-ion beams are powerful mutagens. They cause a broad spectrum of mutation
      phenotypes with high efficiency even at low irradiation doses and short
      irradiation times. These mutagenic effects are due to dense ionisation in a
      localised region along the ion particle path. Linear energy transfer (LET;
      keV.MUm(-1)), which represents the degree of locally deposited energy, is an
      important parameter in heavy-ion mutagenesis. For high LET radiation above 290
      keV?MUm(-1), however, neither the mutation frequency nor the molecular nature of
      the mutations has been fully characterised. In this study, we investigated the
      effect of Fe-ion beams with an LET of 640 keV?MUm(-1) on both the mutation
      frequency and the molecular nature of the mutations. Screening of well
      characterised mutants (hy and gl) revealed that the mutation frequency was lower
      than any other ion species with low LET. We investigated the resulting mutations
      in the 4 identified mutants. Three mutants were examined by employing PCR-based
      methods, one of which had 2-bp deletion, another had 178 bp of tandemly
      duplication, and other one had complicated chromosomal rearrangements with
      variable deletions in size at breakpoints. We also detected large deletions in
      the other mutant by using array comparative genomic hybridisation. From the
      results of the analysis of the breakpoints and junctions of the detected
      deletions, it was revealed that the mutants harboured chromosomal rearrangements
      in their genomes. These results indicate that Fe-ion irradiation tends to cause
      complex mutations with low efficiency. We conclude that Fe-ion irradiation could
      be useful for inducing chromosomal rearrangements or large deletions. 

PMID- 24025248
TI  - Preliminary assessment of differential expression of candidate genes associated
      with atherosclerosis.
AB  - Identifying susceptible genes associated with the pathogenesis of atherosclerosis
      (ATH) may contribute toward better management of this condition. This preliminary
      study was aimed at assessing the expression levels of 11 candidate genes, namely
      tumor protein (TP53), transforming growth factor, beta receptor II (TGFBR2),
      cysthathionenine-beta-synthase (CBS), insulin receptor substrate 1 (IRS1),
      lipoprotein lipase (LPL), methylenetetrahydrofolate reductase (MTHFR),
      thrombomodulin (THBD), lecithin-cholesterol acyltransferase (LCAT), matrix
      metallopeptidase 9 (MMP9), low density lipoprotein receptor (LDLR), and
      arachidonate 5-lipoxygenase-activating protein (ALOX5AP) genes associated with
      ATH. Twelve human coronary artery tissues (HCATs) were obtained from deceased
      subjects who underwent post-mortem procedures. Six atherosclerotic coronary
      artery tissue (ACAT) samples representing the cases and non-atherosclerotic
      coronary artery tissue (NCAT) samples as controls were gathered based on
      predetermined inclusion and exclusion criteria. Gene expression levels were
      assessed using the GenomeLab Genetic Analysis System (GeXP). The results showed
      that LDLR, TP53, and MMP9 expression levels were significantly increased in ACAT
      compared to NCAT samples (p < 0.05). Thus, LDLR, TP53, and MMP9 genes may play
      important roles in the development of ATH in a Malaysian study population. 

PMID- 24025249
TI  - Why do fragile X carrier frequencies differ between Asian and non-Asian
      populations?
AB  - Asian and non-Asian populations have been reported to differ substantially in the
      distribution of fragile X alleles into the normal (< 55 CGG repeats), premutation
      (55-199 CGG repeats), and full-mutation (> 199 CGG repeats) size classes. Our
      statistical analyses of data from published general-population studies confirm
      that Asian populations have markedly lower frequencies of premutation alleles,
      reminiscent of earlier findings for expanded alleles at the Huntington's Disease
      locus. To examine historical and contemporary factors that may have shaped and
      now sustain allele-frequency differences at the fragile X locus, we develop a
      population-genetic/epigenetic model, and apply it to these published data. We
      find that founder-haplotype effects likely contribute to observed frequency
      differences via substantially lower mutation rates in Asian populations. By
      contrast, any premutation frequency differences present in founder populations
      would have disappeared in the several millennia since initial establishment of
      these groups. Differences in the reproductive fitness of female premutation
      carriers arising from fragile X primary ovarian insufficiency (FXPOI) and from
      differences in mean maternal age may also contribute to global variation in
      carrier frequencies. 

PMID- 24025250
TI  - Mitochondrial fission facilitates mitophagy in Saccharomyces cerevisiae.
AB  - As a highly dynamic organelle, mitochondria undergo constitutive fusion and
      fission as well as biogenesis and degradation. Mitophagy, selective mitochondrial
      degradation through autophagy, is a conserved cellular process used for the
      elimination of excessive and damaged mitochondria in eukaryotes. Despite the
      significance of mitophagy in cellular physiology and pathophysiologies, the
      underlying mechanism of this process is far from clear. In this report, we
      studied the role of mitochondrial fission during mitophagy, and uncover a direct
      link between the fission complex and mitophagy machinery in Saccharomyces
      cerevisiae. 

PMID- 24025252
TI  - Ceramide in the prostate.
AB  - The nomenclature for the serine/threonine protein phosphatases was established by
      Professor Sir Philip Cohen over 30 years ago. (1) At that time protein
      phosphatase 1 was known to have two small inhibitory proteins (I-1 and I-2) and
      be regulated by sub-cellular location whereas no protein inhibitor had yet been
      discovered for the related multi-subunit phosphatase PP2A. That paradigm
      subsequently changed, and several PP2A protein inhibitors have been discovered.
      (2) The protein I2PP2A (SET) is considered to be oncogenic, i.e., PP2A is a tumor
      suppressor, and is overexpressed in many tumor cell types (ref. 3, and refs.
      therein). I2PP2A also has other targets besides PP2A, e.g., DNA exonucleases and
      modification of histone acetylation. (4) PP2A activity is known to be regulated
      by the bioactive lipid ceramide, and this occurs through both I2PP2A inhibition
      and PP2A de-repression and through ceramide actions on subunits of the PP2A
      enzyme complex. (5)(,) (6) In the present manuscript the authors examined the
      expression of I2PP2A in prostate cancer and prostate epithelial cells. They
      determined whether ceramide could decrease accumulation of the oncogene c-Myc
      through inhibition of I2PP2A and activation of PP2A. As I2PP2A is also an
      inhibitor of histone acetylation they determined whether ceramide could block the
      epigenetic action of I2PP2A. 

PMID- 24025253
TI  - Multi-kinase modulation for colon cancer therapy.
AB  - It is now well recognized that in the vast majority of tumor types, for the
      approach of "kinase inhibition" to exhibit a significant effect, whether the data
      are from an in vitro assay, an animal model or the clinic, requires that multiple
      complementary kinases be simultaneously inhibited. This combined inhibition is
      not only kill the tumor cell but also to suppress and kill tumor cells that seek
      to avoid the initial induction of death processes via compensatory survival
      signaling mechanisms. Even within the broad brush definition of carcinomas from a
      particular organ, there are a range of mutations which present that will
      profoundly or sometimes more subtly change the paradigm for therapeutic
      intervention using multiple kinase inhibitor combinations. For example, in
      colorectal cancer the K-RAS oncogene frequently has an activating mutation
      implying that inhibition of RAF-MEK1/2-ERK1/2 signaling, but not an initiating
      receptor upstream of K-RAS, could have a therapeutic effect; however, some colon
      cell lines with the K-RAS mutation are still noted to be sensitive to upstream
      ERBB1 inhibitors. Also, compensatory feedback survival signaling loops can cause,
      after inhibition of a mutant active intracellular oncogenic kinase such as B-RAF
      V600E, a survival activation of growth factor receptors in a tumor cell. The
      clinical studies in the manuscript by Al-Marrawi et al. describe the rational
      combination of signaling inhibitors in a colon cancer patient whose tumor cells
      express a mutant active B-RAF V600E protein that signals into the MEK1/2-ERK1/2
      pathway downstream of K-RAS; this is a particularly aggressive form of colon
      cancer for which few rational therapeutic interventions have been available until
      recent times.

PMID- 24025251
TI  - Histone deacetylase inhibitors restore toxic BH3 domain protein expression in
      anoikis-resistant mammary and brain cancer stem cells, thereby enhancing the
      response to anti-ERBB1/ERBB2 therapy.
AB  - The present studies focused on defining the mechanisms by which anoikis-resistant
      (AR) mammary carcinoma cells can be reverted to a therapy-sensitive phenotype. AR
      mammary carcinoma cells had reduced expression of the toxic BH3 domain proteins
      BAX, BAK, NOXA, and PUMA. In AR cells expression of the protective BCL-2 family
      proteins BCL-XL and MCL-1 was increased. AR cells were resistant to cell killing
      by multiple anti-tumor cell therapies, including ERBB1/2 inhibitor + MCL-1
      inhibitor treatment, and had a reduced autophagic flux response to these
      therapies, despite similarly exhibiting increased levels of LC3II processing.
      Knockdown of MCL-1 and BCL-XL caused necro-apoptosis in AR cells to a greater
      extent than in parental cells. Pre-treatment of anoikis-resistant cells with
      histone deacetylase inhibitors (HDACIs) for 24 h increased the levels of toxic
      BH3 domain proteins, reduced MCL-1 levels, and restored/re-sensitized the cell
      death response of AR tumor cells to multiple toxic therapies. In vivo, pre
      treatment of AR breast tumors in the brain with valproate restored the chemo
      sensitivity of the tumors and prolonged animal survival. These data argue that
      one mechanism to enhance the anti-tumor effect of chemotherapy could be HDACI pre
      treatment. 

PMID- 24025254
TI  - Non-canonical p53 signaling to promote invasion.
AB  - It has been known for a number of years that mutated "inactive" p53 proteins
      still capable of binding to DNA per se, can bind to DNA sequences that are non
      canonical for p53, with for example, a resultant increase in the transcription
      and expression of growth factor receptors such as ERBB1, (1)(,) (2) i.e.,
      mutation of p53 not merely results in "no p53 function" but in fact results in
      "oncogenic p53 function". And in agreement with this postulate transduction of
      p53 null cells with mutant p53 can cause transformation. (3) In prior studies the
      authors of the present manuscript had demonstrated that expression of p53 (R175H)
      and ERBB1 could transform immortalized primary esophageal cells, in parallel with
      increased migratory ability. (4) These present studies have defined why those
      transformed cells became invasive: increased c-Met activity. (5.) 

PMID- 24025255
TI  - Janus-faced Kupffer cells in tumor metastasis.
AB  - Kupffer cells are the resident liver macrophages of the liver; other tissues also
      have resident immune cells e.g., microglia in the brain. These cells have a
      distinct embryonic lineage when compared with circulating myeloid cells. In both
      the liver and brain micro-environments activation of their resident immune cells
      results in the synthesis of multiple growth factors and cytokines which stimulate
      tumor growth and that in part provide the permissive "soil" in which the tumor
      "seed" grows. In the manuscript by Wen et al., studies defined whether liver
      localized Kupffer cells supported or inhibited the growth of colorectal tumor
      metastases in an immune competent animal model. The authors also determined
      whether the most important changes in the biology of metastatic tumors were
      associated with the numbers of CD3-positive T cells and the numbers of VEGF and
      iNOS expressing cells.

PMID- 24025256
TI  - PARP inhibitors are not all equal.
AB  - To many investigators PARP1 is simply a substrate for caspase 3, and whose
      cleavage is thought indicative of apoptosis. However, in reality PARP1 plays a
      major role in the biology of the cell cycle and DNA repair. (1)(,) (2) PARP1
      binds to damaged DNA where it becomes enzymatically activated and ADP ribosylates
      itself and other proteins. PARP facilitates DNA repair complex formation, e.g.,
      with BRCA1/2, and the activation of the cell cycle regulatory enzymes ATM and
      ATR. (2) PARP inhibitors as a single agent have only shown any degree of efficacy
      in breast and ovarian cancer patients who lack BRCA1/2 function. (3)(,) (4) The
      present studies examined PARP1 inhibitor biology in a range of triple negative
      and non-triple negative breast cancer cell lines. 

PMID- 24025257
TI  - Arsenic in leukemia: a RSKy business.
AB  - It has been known for many years that arsenic trioxide (As 2O 3; ATO) is an
      effective therapy for acute promyelocytic leukemia but has little activity
      against other forms of the disease. ATO has diverse modes of action, but is well
      known to generate high levels of reactive oxygen species in cells which are
      believed to be causal in many of its biologic actions. ROS can both activate and
      suppress signaling through multiple intracellular pathways based on the amount
      and duration of ROS production. As the basal activity of the MEK1/2-ERK1/2
      pathway is often high in acute myeloid leukemias, and that ATO is known to
      stimulate MEK1/2-ERK1/2 signaling in leukemia, the authors investigated whether
      knock down of the downstream effector of ERK1/2, RSK1, could enhance the anti
      leukemic activity of ATO.

PMID- 24025258
TI  - Targeting inhibitor 2 of protein phosphatase 2A as a therapeutic strategy for
      prostate cancer treatment.
AB  - Inhibitor 2 of protein phosphatase 2A (I2PP2A), a biological inhibitor of the
      cellular serine/threonine protein phosphatase PP2A, is associated with numerous
      cellular processes that often lead to the formation and progression of cancer. In
      this study we hypothesized that targeting the inhibition of I2PP2A's multiple
      functions in prostate cancer cells might prevent cancer progression. We have
      investigated the effect of the small chain C6-ceramide, known to be a bioactive
      tumor suppressor lipid, on I2PP2A function, thereby affecting c-Myc signaling and
      histone acetylation in cells. Our data indicated that C6-ceramide treatment of
      prostate cancer cells induces cell death in PC-3, DU145, and LNCaP cells, but not
      normal prostate epithelial cells. C6-ceramide was able to disrupt the association
      between PP2A and I2PP2A. C6-ceramide inhibits I2PP2A's upregulation of c-Myc and
      downregulation of histone acetylation in prostate cancer cells. Our data
      indicated that targeting cancer related signaling pathways through I2PP2A using
      ceramide as an anti-I2PP2A agent could have beneficial effects as a therapeutic
      approach to prevent prostate cancer. 

PMID- 24025259
TI  - Even mild hyperlactatemia is associated with increased mortality in critically
      ill patients.
AB  - INTRODUCTION: The clinical significance of elevation of lactate levels within the
      reference range is not well studied. The objective of this study was to determine
      the best cutoff threshold for serum lactate within the reference range (0.01 to
      2.00 mM) that best discriminated between survivors and nonsurvivors of critical
      illness and to examine the association between relative hyperlactatemia (lactate
      above the identified threshold) and mortality. METHODS: This was a retrospective
      cohort study of adult patients admitted to the medical-surgical intensive care
      unit (ICU) of a tertiary care academic center. Youden index was calculated to
      identify the best lactate cutoff threshold that discriminated between survivors
      and nonsurvivors. Patients with lactate above the identified threshold were
      defined as having relative hyperlactatemia. Multivariate logistic regression,
      adjusting for baseline variables, was performed to determine the relationship
      between the above two ranges of lactate levels and mortality. In addition, a test
      of interaction was performed to assess the effect of selected subgroups on the
      association between relative hyperlactatemia and hospital mortality. RESULTS:
      During the study period, 2,157 patients were included in the study with mean
      lactate of 1.3 +/- 0.4 mM, age of 55.1 +/- 20.3 years, and acute physiology and
      chronic health evaluation (APACHE) II score of 22.1 +/- 8.2. Vasopressors were
      required in 42.4%. Lactate of 1.35 mM was found to be the best cutoff threshold
      for the whole cohort. Relative hyperlactatemia was associated with increased
      hospital mortality (adjusted odds ratio (aOR), 1.60, 95% confidence interval (CI)
      1.29 to 1.98), and ICU mortality (aOR, 1.66; 95% CI, 1.26 to 2.17) compared with
      a lactate level of 0.01 to 1.35 mM. This association was consistent among all
      examined subgroups. CONCLUSIONS: Relative hyperlactatemia (lactate of 1.36 to
      2.00 mM) within the first 24 hours of ICU admission is an independent predictor
      of hospital and ICU mortality in critically ill patients.

PMID- 24025260
TI  - Intensive exercise program after spinal cord injury ("Full-On"): study protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Rehabilitation after spinal cord injury (SCI) has traditionally
      involved teaching compensatory strategies for identified impairments and deficits
      in order to improve functional independence. There is some evidence that regular
      and intensive activity-based therapies, directed at activation of the paralyzed
      extremities, promotes neurological improvement. The aim of this study is to
      compare the effects of a 12-week intensive activity-based therapy program for the
      whole body with a program of upper body exercise. METHODS/DESIGN: A multicenter,
      parallel group, assessor-blinded randomized controlled trial will be conducted.
      One hundred eighty-eight participants with spinal cord injury, who have completed
      their primary rehabilitation at least 6 months prior, will be recruited from five
      SCI units in Australia and New Zealand. Participants will be randomized to an
      experimental or control group. Experimental participants will receive a 12-week
      program of intensive exercise for the whole body, including locomotor training,
      trunk exercises and functional electrical stimulation-assisted cycling. Control
      participants will receive a 12-week intensive upper body exercise program. The
      primary outcome is the American Spinal Injuries Association (ASIA) Motor Score.
      Secondary outcomes include measurements of sensation, function, pain,
      psychological measures, quality of life and cost effectiveness. All outcomes will
      be measured at baseline, 12 weeks, 6 months and 12 months by blinded assessors.
      Recruitment commenced in January 2011. DISCUSSION: The results of this trial will
      determine the effectiveness of a 12-week program of intensive exercise for the
      whole body in improving neurological recovery after spinal cord injury. TRIAL
      REGISTRATION: NCT01236976 (10 November 2010), ACTRN12610000498099 (17 June 2010).

PMID- 24025261
TI  - Activated caspase detection in living tissue combined with subsequent retrograde
      labeling, immunohistochemistry or in situ hybridization in whole-mounted lamprey
      brains.
AB  - In the lamprey brain, there are 18 pairs of identified spinal-projecting neurons
      whose regenerative abilities have been characterized. The "bad-regenerating"
      neurons show a very delayed form of apoptosis after axotomy (Shifman et al.,
      2008). Theoretically, this should provide a long window of opportunity to
      intervene therapeutically, so it would be helpful if we could identify the early
      stages of this process in vivo. Until now, there has been no method to link mRNA
      or protein expression directly to early-stages neuronal apoptosis in vivo. Here
      we describe a double-labeling protocol in whole-mounted lamprey brain for
      simultaneous detection of early stage apoptosis, using Fluorochrome-Labeled
      Inhibitors of Caspases (FLICA), and either mRNA, using in situ hybridization, or
      protein expression, using immunohistochemistry. To improve brain preservation,
      the working temperature during the FLICA stage was lowered from 37 degrees C to 4
      degrees C (Barreiro-Iglesias and Shifman, 2012). Using this method, neurofilament
      protein was demonstrated by immunohistochemistry in neurons previously reacted by
      FLICA. The method also revealed that mRNA for the receptor protein tyrosine
      phosphatase PTPsigma is expressed selectively in FLICA-positive neurons. In
      addition, our study showed that a retrograde labeling technique can be used in
      the context of FLICA labeling. FLICA label colocalized with TUNEL staining,
      confirming that FLICA labeling is a reliable marker of apoptosis in lamprey
      brain. Our results suggested that we can combine caspase detection with other
      techniques in vivo to investigate the roles and mechanisms of activated caspases
      and other molecules in retrograde cell deaths and regenerative abilities of
      neurons.

PMID- 24025262
TI  - Light-microscope specimen holder with 3-axis rotation and small-angle control.
AB  - BACKGROUND: Although recent developments in methodologies for light microscopy
      have enabled imaging of fine biological structures, such imaging is often
      accompanied by two types of problems. One is a tilting of the specimen with
      respect to the x-y plane (i.e. rotation around the x- or y-axis) such that the
      sample is not perpendicular to the optical z-axis, and the other is rotation
      around the z-axis that precludes optimal orientations for imaging and
      experimentation. These rotation problems can cause optical aberrations and hamper
      imaging experiments, even when the angular difference from the ideal position is
      small. NEW METHOD: In order to correct for these practical issues, we have
      developed a specimen holder with 3-axis (x-y-z) rotation for an inverted light
      microscope. This allows for full-range rotations of 2-4 degrees  for x-, y-axes,
      ~24 degrees  for z-axis, and a small-angle control of <0.1 degrees  for either
      axis. RESULTS: Using this device, we observed the cultured hippocampal neurons
      stained by immunofluorescence for a dendritic marker, or the sub-resolution
      fluorescent beads plated on a glass coverslip. The rotations and associated
      problems could be manipulated, while viewing the specimens by laser-scanning
      confocal microscopy. COMPARISON WITH EXISTING METHODS: This tilting/rotation
      device is easily manufactured and installed on a conventional microscope stage
      without requiring changes to the existing optical components. Similar devices
      with full capability have not been available. CONCLUSIONS: It will be useful for
      imaging experiments with biomedical applications.

PMID- 24025275
TI  - Acute management of a unilateral incarcerated Spigelian hernia in a patient with
      bilateral Spigelian hernias.
AB  - Spigelian hernias were first described by Joseph Klinkosch in the 18th century,
      and have since posed a diagnostic and surgical problem owing to their non
      specific presentation and rarity. While the management of unilateral hernias is
      fairly well described in today's literature, bilateral Spigelian hernias are very
      rare. We describe the emergency management of a patient with bilateral Spigelian
      hernias, diagnosed on computed tomography. 

PMID- 24025276
TI  - Actinomycosis: an unusual cause of unresectable rectal cancer.
AB  - We present a very unusual case of a woman with an intrauterine contraceptive
      device (IUCD) who developed pelvic actinomycosis during long course
      chemoradiotherapy for rectal cancer, which presented a significant diagnostic
      challenge and eventually rendered the cancer unresectable. IUCDs are often
      implicated in the development of pelvic actinomycosis but there is no current
      evidence or guideline to suggest that they should be removed prior to oncological
      treatment. Owing to the devastating consequences of this combination of disease,
      we suggest that it may be prudent to remove IUCDs in this setting. 

PMID- 24025277
TI  - Total mesorectal excision for cancer following ventral mesh rectopexy.
AB  - Since the introduction of ventral mesh rectopexy for rectal prolapse, concern
      exists as to how this may interfere with subsequent rectal cancer surgery. To our
      knowledge, this is the first report of total mesorectal excision for cancer after
      such a rectopexy. We discuss surgical technique, pitfalls encountered and
      oncological outcome. 

PMID- 24025278
TI  - Littre meets de Garengeot: Meckel's diverticulum and appendix in a femoral
      hernia.
AB  - Littre's and de Garengeot hernias are rare operative findings, the former
      describing the presence of a Meckel's diverticulum in a hernia sac and the latter
      describing the presence of the vermiform appendix in a femoral hernia. The
      finding of both of these anatomical structures in the same hernia is exquisitely
      rare and infrequently described. In the following report such a case is described
      and the current knowledge surrounding these unusual hernias is discussed. 

PMID- 24025280
TI  - Obstructed hepatic flexure contained in a right-sided inguinoscrotal hernia
      resulting in caecal perforation.
AB  - Inguinal hernia often presents as an emergency with obstruction and subsequent
      strangulation. We report a unique case where an inguinoscrotal sliding type
      hernia contained the entire hepatic flexure as its lead point, resulting in acute
      colonic obstruction and caecal wall perforation. 

PMID- 24025279
TI  - Acute gastric necrosis after routine oesophagogastroduodenoscopy with therapeutic
      argon plasma coagulation.
AB  - A 56-year-old woman presented to the accident and emergency department with
      peritonitis 2 days after a routine oesophagogastroduodenoscopy. She was taken to
      theatre with the finding of gastric necrosis. Blood and peritoneal cultures grew
      group A haemolytic Streptococcus. Histology revealed normal vasculature, no
      volvulus but marked neutrophilia in the submucosa with an intact mucosa. The
      stomach was resected and the patient recovered in the intensive care unit but
      overwhelming acidosis progressed to multiorgan failure and treatment was
      eventually withdrawn. Acute phlegmonous gastritis has been well described in the
      literature but mainly before the advent of antibiotics. The most common organism
      is group A haemolytic Streptococcus (commonly found in throat infections) and
      predisposing factors include instrumentation. Should antibiotics be given at the
      start of an oesophagogastroduodenoscopy and should routine procedures be delayed
      if active upper respiratory tract infections are present? 

PMID- 24025281
TI  - Anaphylactic reaction to intraurethral chlorhexidine: sensitisation following
      previous repeated uneventful administration.
AB  - Instillagel((r)) (CliniMed, High Wycombe, UK) is commonly used in urethral
      catheterisation and to facilitate the passage of instruments into the bladder in
      urological practice. Its active ingredients include 0.25% chlorhexidine, 2%
      lidocaine, 0.06% methyl hydroxybenzoate and 0.025% propyl hydroxybenzoate. We
      discuss the case of an 84-year-old man who received intraurethral
      Instillagel((r)) prior to laser ablation of a recurrent transitional cell
      carcinoma of the bladder, resulting in anaphylaxis. Subsequent investigation
      confirmed allergy to chlorhexidine. Although there are previous reports in the
      literature, this is the first report of intraurethral chlorhexidine resulting in
      anaphylaxis in a patient who had had repeated, uneventful previous exposures. As
      such, this case illustrates the phenomenon of chlorhexidine sensitisation and
      that previous uneventful exposures do not exclude the diagnosis of anaphylaxis in
      the context of sudden, unexpected deterioration. 

PMID- 24025283
TI  - Case-based review: bile peritonitis after T-tube removal.
AB  - T-tube placement into the common bile duct (CBD) is most commonly performed after
      CBD exploration for cholelithiasis or repair of an iatrogenic CBD injury. Bile
      peritonitis occurring after T-tube removal is generally considered an exceedingly
      rare complication, which on occurrence necessitates urgent intervention. No clear
      guidance exists on the timing of T-tube removal and its relationship to the
      development of bile peritonitis. This study aimed to determine the incidence of
      bile peritonitis after T-tube removal, its relationship to the timing of removal
      and how knowledge of this can help the general surgeon. 

PMID- 24025284
TI  - An evidence-based review of enhanced recovery interventions in knee replacement
      surgery.
AB  - INTRODUCTION: Total knee replacement (TKR) is a very common surgical procedure.
      Improved pain management techniques, surgical practices and the introduction of
      novel interventions have enhanced the patient's postoperative experience after
      TKR. Safe, efficient pathways are needed to address the increasing need for knee
      arthroplasty in the UK. Enhanced recovery programmes can help to reduce hospital
      stays following knee replacements while maintaining patient safety and
      satisfaction. This review outlines common evidence-based pre, intra and
      postoperative interventions in use in enhanced recovery protocols following TKR.
      METHODS: A thorough literature search of the electronic healthcare databases
      (MEDLINE((r)), EmbaseTM and the Cochrane Library) was conducted to identify
      articles and studies concerned with enhanced recovery and fast track pathways for
      TKR. RESULTS: A literature review revealed several non-operative and operative
      interventions that are effective in enhanced recovery following TKR including
      preoperative patient education, pre-emptive and local infiltration analgesia,
      preoperative nutrition, neuromuscular electrical stimulation, pulsed
      electromagnetic fields, perioperative rehabilitation, modern wound dressings,
      different standard surgical techniques, minimally invasive surgery and computer
      assisted surgery. CONCLUSIONS: Enhanced recovery programmes require a
      multidisciplinary team of dedicated professionals, principally involving
      preoperative education, multimodal pain control and accelerated rehabilitation;
      this will be boosted if combined with minimally invasive surgery. The current
      economic climate and restricted healthcare budget further necessitate brief
      hospitalisation while minimising costs. These non-operative interventions are the
      way forward to achieve such requirements.

PMID- 24025285
TI  - Oedema is associated with clinical outcome following emergency abdominal surgery.
AB  - INTRODUCTION: Oedema is observed frequently following surgery and may be
      associated with worse outcomes. To date, no study has investigated the role of
      oedema in the emergency surgical patient. This study assesses the incidence of
      oedema following emergency abdominal surgery and the value of early postoperative
      oedema measurement in predicting clinical outcome. METHODS: A prospective cohort
      study of patients undergoing emergency abdominal surgery at a university unit
      over a two-month period was undertaken. Nutritional and clinical outcome data
      were collected and oedema was measured in the early postoperative period.
      Predictors of oedema and outcomes associated with postoperative oedema were
      identified through univariate and multivariate analysis. RESULTS: Overall, 55
      patients (median age: 66 years) were included in the study. Postoperative
      morbidity included ileus (n=22) and sepsis (n=6) with 12 deaths at follow-up.
      Postoperative oedema was present in 19 patients and was associated with prolonged
      perioperative fasting (107 vs 30 hours, p=0.009) but not with body mass index (24
      kg/m(2) vs 27 kg/m(2), p=0.169) or preadmission weight loss (5% vs 3%, p=0.923).
      On multivariate analysis, oedema was independently associated with
      gastrointestinal recovery (B=6.91, p=0.038), artificial nutritional support
      requirement (odds ratio: 6.91, p=0.037) and overall survival (chi(2) =13.1, df=1,
      p=0.001). CONCLUSIONS: Generalised oedema is common after emergency abdominal
      surgery and appears to independently predict gastrointestinal recovery, the need
      for artificial nutritional support and survival. Oedema is not associated with
      commonly applied markers of nutritional status such as body mass index or recent
      weight loss. Measurement of oedema offers utility in identifying those at risk of
      poor clinical outcome or those requiring artificial nutritional support following
      emergency abdominal surgery.

PMID- 24025286
TI  - The faciocervicopectoral flap for non-oncological cases of cheek reconstruction.
AB  - INTRODUCTION: Major facial defect has been a challenging case for plastic
      surgeons in terms of wound healing and covering technique for a long time.
      METHODS: Eight faciocervicopectoral (FCP) flaps were performed for reconstruction
      of major cheek defects due to handmade explosive and gun injuries. They were
      evaluated perioperatively and postoperatively with regard to operative time and
      operative blood loss as well as the function and cosmetic appearance. RESULTS:
      The technique showed marvellous cosmetic results but encountered minor
      postoperative flap complications. CONCLUSIONS: The FCP flap is one of the best
      solutions for coverage of a simple or complex cheek defect. Application of the
      FCP flap is easy and rapid.

PMID- 24025287
TI  - A critical inventory of preoperative skull replicas.
AB  - INTRODUCTION: Physical replicas of organs are used increasingly for preoperative
      planning. The quality of these models is generally accepted by surgeons. In view
      of the strong trend towards minimally invasive and personalised surgery, however,
      the aim of this investigation was to assess qualitatively the accuracy of such
      replicas, using skull models as an example. METHODS: Skull imaging was acquired
      for three cadavers by computed tomography using clinical routine parameters.
      After digital three-dimensional (3D) reconstruction, physical replicas were
      produced by 3D printing. The facsimilia were analysed systematically and compared
      with the best gold standard possible: the macerated skull itself. RESULTS: The
      skull models were far from anatomically accurate. Non-conforming rendering was
      observed in particular for foramina, sutures, notches, fissures, grooves,
      channels, tuberosities, thin-walled structures, sharp peaks and crests, and
      teeth. CONCLUSIONS: Surgeons should be aware that preoperative models may not yet
      render the exact anatomy of the patient under consideration and are advised to
      continue relying, in specific conditions, on their own analysis of the native
      computed tomography or magnetic resonance imaging.

PMID- 24025288
TI  - Absence of the genicular arterial anastomosis as generally depicted in textbooks.
AB  - INTRODUCTION: Textbook representations of the genicular arterial anastomosis show
      a large direct communication between the descending branch of the lateral
      circumflex femoral artery (DBLCFA) and a genicular branch of the popliteal artery
      but this is not compatible with clinical experience. The aim of this study was to
      determine whether the arterial anastomosis at the knee is sufficient, in the
      event of traumatic disruption of the superficial femoral artery, to infuse
      protective agents or to place a stent to restore flow to the lower leg. METHODS:
      Dissection of ten cadaveric lower limbs was performed to photograph the arterial
      anatomy from the inguinal ligament to the tibial tubercle. Anastomosis with
      branches of the popliteal artery was classified as: 'direct communication',
      'approaching communication' or 'no evident communication'. RESULTS: A constant
      descending artery in the lateral thigh (LDAT) was found to have five types of
      origin: Type 1 (2/10 limbs) involved the lateral circumflex femoral branch of the
      femoral artery, Type 2 (3/10 limbs) the lateral circumflex femoral branch of the
      profunda femoris artery, Type 3 (1/10 limbs) the femoral artery, Type 4 (3/10
      limbs) the superficial femoral artery and Type 5 (2/10 limbs) the profunda
      femoris artery. In one limb, there were two descending arteries (Types 4 and 5).
      Collateral circulation at the knee was also variable: direct communicating
      vessels (3/10 limbs); approaching vessels with possible communication via
      capillaries (5/10 limbs); no evident communication (2/10 limbs). Communicating
      vessels, if present, are too small to provide immediate collateral circulation.
      CONCLUSIONS: Modern representations of the genicular arterial anastomosis are
      inaccurate, derived commonly from an idealised image that first appeared Gray's
      Anatomy in 1910. The afferent vessel is not the DBLCFA. The majority of subjects
      have the potential to recruit collateral circulation via the LDAT following
      gradual obstruction to normal arterial flow, which may be important if the LDAT
      is removed for bypass or flap surgery. A direct communication is rarely present
      and is never as robust as generally depicted in textbooks.

PMID- 24025289
TI  - Application of the Paediatric Throat Disorders Outcome Test (T-14) for
      tonsillectomy and adenotonsillectomy.
AB  - INTRODUCTION: The T-14 questionnaire is a validated patient reported outcome
      measure (PROM) used to assess the value of paediatric tonsillectomy from the
      patient's perspective. Tonsillectomy is a procedure under threat. As such, this
      study aimed to provide further evidence supporting the role of tonsillectomy in
      the management of recurrent tonsillitis and obstructive sleep apnoea. METHODS: A
      prospective uncontrolled observational study was undertaken examining 54
      paediatric patients undergoing tonsillectomy at our institution. Parents of
      children having surgery were invited to complete a T-14 questionnaire
      preoperatively as well as at three and six months postoperatively. RESULTS: The
      questionnaire was completed for 52 of the 54 patients preoperatively as well as
      at 3 and 6 months postoperatively (96% response rate). The mean difference
      between the preoperative and six-month T-14 score was 31.8 (p<0.0001). T-14
      scores at three months were also significantly improved compared with those taken
      preoperatively (mean difference: 29.9, p<0.0001). CONCLUSIONS: This is the first
      study in the literature to assess T-14 questionnaires at three and six months
      following paediatric tonsillectomy, providing evidence of the early benefit on
      PROMs. Tonsillectomy is the most common surgical procedure performed in the UK,
      and it is regarded highly by patients and otolaryngologists alike. This study
      provides significant evidence that tonsillectomy improves PROMs, thereby
      demonstrating its ongoing clinical value as a funded National Health Service
      procedure.

PMID- 24025290
TI  - Oxford elbow scores in an asymptomatic population.
AB  - INTRODUCTION: Patient reported outcome measures (PROMs) are being used
      increasingly to assess the quality of healthcare delivery in the UK. It is
      important when using PROMs to know the score of the background population against
      which any clinical intervention may be benchmarked. The purpose of this study was
      to measure an elbow specific PROM for the population of the South West Peninsula.
      METHODS: A cross-sectional survey was undertaken of patients and healthcare
      professionals from the South West Peninsula population. Participants were asked
      to complete a simple demographic questionnaire and an Oxford elbow score for each
      elbow. Respondents with a history of elbow surgery, elbow injury, chronic elbow
      problems or an incomplete dataset were excluded from the study. RESULTS: A total
      of 1,765 respondents (3,530 elbows) completed the survey but 567 questionnaires
      were excluded due to incomplete datasets, pre-existing elbow pathology or age
      criteria, leaving 1,198 individuals (2,396 elbows) for analysis. The median
      scores for each decade group were 48, with mean scores ranging from 46.74 to
      47.94. There was no significant clinical difference in the scores for age, sex or
      hand dominance. CONCLUSIONS: When using the Oxford elbow score to assess outcomes
      after surgery, a normal score should be used as the benchmark. This benchmark is
      independent of age, sex and hand dominance.

PMID- 24025291
TI  - Accuracy of internet images of glenoid labral injuries.
AB  - INTRODUCTION: The internet is a convenient source of health information used
      widely by patients and doctors. Previous studies have found that the written
      information provided was often inaccurate. There is no literature regarding the
      accuracy of medical images on the internet. The aim of this study was to assess
      the accuracy of internet images of injuries to the glenoid labrum following
      shoulder dislocation. METHODS: The Google and Bing search engines were used to
      find images of Bankart, Perthes and anterior labroligamentous periosteal sleeve
      avulsion (ALPSA) lesions. Three independent reviewers assessed the accuracy of
      image labelling. RESULTS: Of images labelled 'Bankart lesion', 30% (9/30) were
      incorrect while 'Perthes lesion' images were incorrect in 15% of cases (9/60) and
      4% of 'ALPSA lesion' images were incorrect (2/46). There was good interobserver
      reliability (kappa = 0.81). Labelling accuracy was better on educational sites
      than on commercial sites (6% vs 25% inaccurate, p=0.0013). CONCLUSIONS: Caution
      is recommended when interpreting non-peer reviewed images on the internet.

PMID- 24025292
TI  - Three-dimensional assessment of hand outcome.
AB  - INTRODUCTION: Patient reported outcome measures are central to National Health
      Service quality of care assessments. This study investigated the benefit of
      elective hand surgery by the simultaneous analysis of pain, function and
      appearance, using a three-dimensional (3D) graphical model for evaluating and
      presenting outcome. METHODS: A total of 188 patients scheduled for surgery
      completed pre- and postoperative questionnaires grading the severity of their
      pain, dysfunction and deformity of their hand(s). Scores were plotted on a 3D
      graph to demonstrate the degree of 'normalisation' following surgery. RESULTS:
      Surgical groups included: nerve compression (n=53), Dupuytren's disease (n=51),
      trigger finger (n=20), ganglion (n=17) or other lump (n=21), trapeziometacarpal
      joint osteoarthritis (n=10), rheumatoid disease (n=5) and other pathology (n=13).
      A significant improvement towards normality was seen after surgery in each group
      except for patients with rheumatoid disease. CONCLUSIONS: This study provides a
      simple, visual representation of hand surgery outcome by plotting patient scores
      for pain, function and appearance simultaneously on a 3D graph.

PMID- 24025293
TI  - Indications and early to mid-term results of ulnar head replacement.
AB  - INTRODUCTION: The aim of this study was to explore the indications and show the
      early to mid-term results of ulnar head replacement for the treatment of
      pathological conditions of the distal radioulnar joint. METHODS: Our study group
      comprised 52 patients with a mean age of 64 years who had 56 ulnar head
      replacements. Seven were implanted to salvage an unstable deletive procedure; the
      rest were for primary treatment of osteoarthritis, rheumatoid arthritis and
      trauma. Concomitant procedures along with the ulnar head replacement included
      wrist arthrodesis, joint replacement and tendon transfers. RESULTS: The follow-up
      duration ranged from 1 year to 11 years (mean: 60 months, median: 60 months). In
      almost all of the patients, pain improved with a median visual analogue scale
      score of 2 (mean: 2.2, range: 0-8) and a median DASH (Disabilities of the Arm,
      Shoulder and Hand) score of 12.5 (mean: 17.9, range: 0-56). Of the 52 patients,
      47 reported they would have the same procedure again. CONCLUSIONS: Ulnar head
      replacement appears to be a reliable and effective procedure solving several
      pathological problems of the distal radioulnar joint. We present a large patient
      group with a short to medium-term follow-up duration.

PMID- 24025294
TI  - NICE thromboprophylaxis guidelines are not associated with increased pericardial
      effusion after surgery of the proximal thoracic aorta.
AB  - INTRODUCTION: In 2010 the National Institute for Health and Clinical Excellence
      (NICE) released guidelines on venous thromboembolism. Strategy focused on risk
      assessment, antiembolic stockings, sequential compression devices, subcutaneous
      high dose enoxaparin (40 mg), early mobilisation and hydration. The 40 mg
      enoxaparin dose over the previous 20 mg regimen was worrisome, and its effect on
      pericardial effusion rates and mortality in proximal aortic surgery was
      investigated. METHODS: Proximal aortic reconstructions performed between December
      2008 and April 2011 were identified from prospectively collected data in a
      tertiary centre database. Retrospective analysis of patient notes was performed.
      Proximal aortic surgery patients were categorised as low dose (20 mg) enoxaparin
      and high dose (40 mg) enoxaparin, and compared for confounding variables. In
      hospital, early and one-year readmission rates for pericardial effusion were
      ascertained from echocardiography reports. The primary outcome was total
      pericardial effusion rate. Secondary outcomes consisted of 30-day and 1-year
      mortality. RESULTS: A total of 198 patients underwent proximal thoracic aortic
      surgery. Nine patients were excluded due to early postoperative death (n=5) and
      missing patient records (n=4). This left 189 cases for analysis. There were 93
      patients in the low dose group and 96 in the high dose group. Groups were
      comparable for age, cardiopulmonary bypass time, aortic cross-clamp time,
      postoperative warfarin and antiplatelet agents. Pericardial effusion rates up to
      one year were comparable (low dose 19% vs high dose 21%). Thirty-day mortality
      was lower in the low dose group (0 vs 3 deaths). There were four deaths up to one
      year but these were not attributable to increased enoxaparin. CONCLUSIONS:
      Increased perioperative thromboprophylaxis dosage does not increase pericardial
      effusion rates or mortality in proximal aortic surgery.

PMID- 24025295
TI  - A novel latex-free alternative to a proprietary paper framed dental rubber dam.

PMID- 24025296
TI  - Twist-over: stainless steel suture technique for skin graft applications.

PMID- 24025297
TI  - A simple method to optimise graft tailoring in ascending aorta replacement.

PMID- 24025298
TI  - Technical tip for knee arthroscopy.

PMID- 24025299
TI  - Use of an intravenous cannula as a laparoscopic extracorporeal knot pusher.

PMID- 24025300
TI  - Use of plastic gallipot to protect soft tissues during insertion of static cement
      spacer in revision total knee arthroplasty.

PMID- 24025301
TI  - A simple technique for intraoperative decompression of obstructed bowel.

PMID- 24025302
TI  - Uterine flap: a simple method to reconstruct perineal defect following
      extralevator abdominoperineal resection in women.

PMID- 24025303
TI  - Rectus sheath catheterisation: a novel method of placement.

PMID- 24025304
TI  - The diamond frame: a simple and reliable construct for damage control
      resuscitation for femoral and knee spanning external fixation.

PMID- 24025305
TI  - A novel technique for removing renal calculi during laparoscopic pyeloplasty.

PMID- 24025306
TI  - A simple method of postgastric bypass laparoscopic-assisted endoscopic retrograde
      cholangiopancreatography.

PMID- 24025307
TI  - The poke test in lower limb fasciotomy.

PMID- 24025308
TI  - Biplanar imaging for intramedullary nailing of tibia and femur.

PMID- 24025309
TI  - Topical steroids for chronic wounds displaying abnormal inflammation.

PMID- 24025311
TI  - Paramagnetism and antiferromagnetic interactions in single-phase Fe-implanted
      ZnO.
AB  - As the intrinsic origin of the high-temperature ferromagnetism often observed in
      wide-gap dilute magnetic semiconductors becomes increasingly debated, there is a
      growing need for comprehensive studies on the single-phase region of the phase
      diagram of these materials. Here we report on the magnetic and structural
      properties of Fe-doped ZnO prepared by ion implantation of ZnO single crystals. A
      detailed structural characterization shows that the Fe impurities substitute for
      Zn in ZnO in a wurtzite Zn(1-x)Fe(x)O phase which is coherent with the ZnO host.
      In addition, the density of beam-induced defects is progressively decreased by
      thermal annealing up to 900  degrees  C, from highly disordered after
      implantation to highly crystalline upon subsequent annealing. Based on a detailed
      analysis of the magnetometry data, we demonstrate that isolated Fe impurities
      occupying Zn-substitutional sites behave as localized paramagnetic moments down
      to 2 K, irrespective of the Fe concentration and the density of beam-induced
      defects. With increasing local concentration of Zn-substitutional Fe, strong
      nearest-cation-neighbor antiferromagnetic interactions favor the antiparallel
      alignment of the Fe moments.

PMID- 24025312
TI  - Assessment of the efficiency of in situ bioremediation techniques in a creosote
      polluted soil: change in bacterial community.
AB  - This work aimed to assess the effectiveness of different in situ bioremediation
      treatments (bioaugmentation, biostimulation, bioaugmentation and biostimulation,
      and natural attenuation) on creosote polluted soil. Toxicity, microbial
      respiration, creosote degradation and the evolution of bacterial communities were
      analyzed. Results showed that creosote decreased significantly in all treatments,
      and no significant differences were found between treatments. However, some
      specific polycyclic aromatic hydrocarbons (PAH) were degraded to a greater extent
      by biostimulation. The dominance of low temperatures (8.9  degrees C average)
      slowed down microbial creosote and PAH uptake and, despite significantly creosote
      degradation (>60%) at the end of the experiment, toxicity remained constant and
      high throughout the biodegradation process. DGGE results revealed that
      biostimulation showed the highest microbial biodiversity, although at the end of
      the biodegradation process, community composition in all treatments was different
      from that of the control assay (unpolluted soil). The active uncultured bacteria
      belonged to the genera Pseudomonas, Sphingomonas, Flexibacter, Pantoea and
      Balneimonas, the latter two of which have not been previously described as PAH
      degraders. The majority of the species identified during the creosote
      biodegradation belonged to Pseudomonas genus, which has been widely studied in
      bioremediation processes. Results confirmed that some bacteria have an intrinsic
      capacity to degrade the creosote without previous exposure.

PMID- 24025313
TI  - Layers of protection analysis in the framework of possibility theory.
AB  - An important issue faced by risk analysts is how to deal with uncertainties
      associated with accident scenarios. In industry, one often uses single values
      derived from historical data or literature to estimate events probability or
      their frequency. However, both dynamic environments of systems and the need to
      consider rare component failures may make unrealistic this kind of data. In this
      paper, uncertainty encountered in Layers Of Protection Analysis (LOPA) is
      considered in the framework of possibility theory. Data provided by reliability
      databases and/or experts judgments are represented by fuzzy quantities
      (possibilities). The fuzzy outcome frequency is calculated by extended
      multiplication using alpha-cuts method. The fuzzy outcome is compared to a
      scenario risk tolerance criteria and the required reduction is obtained by
      resolving a possibilistic decision-making problem under necessity constraint. In
      order to validate the proposed model, a case study concerning the protection
      layers of an operational heater is carried out. 

PMID- 24025314
TI  - Health risk assessment of inhalation exposure of irrigation workers and the
      public to trihalomethanes from reclaimed water in landscape irrigation in
      Tianjin, North China.
AB  - To estimate the concentration in air and the cancer risk of irrigation workers
      and the public exposed to the total trihalomethanes (TTHMs) in reclaimed water
      used for landscape irrigation, a probabilistic health risk assessment was
      conducted through the integrated use of one-dimensional (1-D) and two-dimensional
      (2-D) Monte Carlo simulations. Before the 2-D simulation, a sensitivity analysis
      corresponding to the 1-D simulation was carried out to identity the factors most
      affecting the outputs. The results reveal that the TTHM concentration level and
      cancer risk for workers' exposure is much higher than that for public exposure in
      landscape irrigation. Moreover, the most influential factors are quite different
      for workers' exposure and public exposure. The 2-D Monte Carlo risk analysis
      result for the workers indicated that the lowest-risk, highest-risk and two
      critical points for irrigation height are 0.7 m, 1.53 m, 1.4m and 1.65 m when the
      mean value of the risk is selected as the reference statistic for risk
      management. Based on the risk assessment results, different measures can be
      suggested for the risk control of different populations. Furthermore, the
      influential variables should be better characterized to improve the accuracy of
      health risk assessment.

PMID- 24025315
TI  - Motor phenotype and magnetic resonance measures of basal ganglia iron levels in
      Parkinson's disease.
AB  - BACKGROUND: In Parkinson's disease the degree of motor impairment can be
      classified with respect to tremor dominant and akinetic rigid features. While
      tremor dominance and akinetic rigidity might represent two ends of a continuum
      rather than discrete entities, it would be important to have non-invasive markers
      of any biological differences between them in vivo, to assess disease
      trajectories and response to treatment, as well as providing insights into the
      underlying mechanisms contributing to heterogeneity within the Parkinson's
      disease population. METHODS: Here, we used magnetic resonance imaging to examine
      whether Parkinson's disease patients exhibit structural changes within the basal
      ganglia that might relate to motor phenotype. Specifically, we examined volumes
      of basal ganglia regions, as well as transverse relaxation rate (a putative
      marker of iron load) and magnetization transfer saturation (considered to index
      structural integrity) within these regions in 40 individuals. RESULTS: We found
      decreased volume and reduced magnetization transfer within the substantia nigra
      in Parkinson's disease patients compared to healthy controls. Importantly, there
      was a positive correlation between tremulous motor phenotype and transverse
      relaxation rate (reflecting iron load) within the putamen, caudate and thalamus.
      CONCLUSIONS: Our findings suggest that akinetic rigid and tremor dominant
      symptoms of Parkinson's disease might be differentiated on the basis of the
      transverse relaxation rate within specific basal ganglia structures. Moreover,
      they suggest that iron load within the basal ganglia makes an important
      contribution to motor phenotype, a key prognostic indicator of disease
      progression in Parkinson's disease.

PMID- 24025316
TI  - TB treatment outcomes among TB-HIV co-infections in Karnataka, India: how do
      these compare with non-HIV tuberculosis outcomes in the province?
AB  - BACKGROUND: India accounts for 23% of the global incidence of TB cases; it also
      has an estimated 2.3 million HIV infections. Of the 2 million TB incident cases,
      5% occurred in HIV infected persons. The country has large national TB and HIV
      control programs. This paper describes characteristics of TB-HIV co-infection
      cases registered under the program in Karnataka province, India. Treatment
      outcomes for coinfected patients are compared with those for TB patients in the
      province. METHODS: Program reports from the National AIDS Control program and the
      National TB control program for Karnataka province (a high HIV prevalence state,
      population 61 million) were analysed. Data from patients registered in each
      program in 2010-2011 was studied. RESULTS: Of the 6,480 adult co-infections, a
      third occurred in women; 78% of patients were initiated on ART. Among the cohort
      73% had pulmonary TB, and 46% reported sputum positivity for acid fast bacilli.
      Treatment success among co-infected patients not on ART (54%) were significantly
      lower compared to those already on ART (80%); death and default rates were higher
      in the non-ART group. Treatment success proportions (75%) for the co-infected
      patients were similar to those for the 51,966 patients registered under the TB
      program. Death rates among co-infected patients (15%) were twice as high as for
      TB patients under the program, though default and failure rates were lower.
      CONCLUSION: Co-infected patients already on ART demonstrated better TB outcomes
      in than those not on ART. Compared to those with TB only, co-infected patients
      had similar TB treatment success rates and lower rates of treatment default and
      failure. Integration of TB-HIV collaborative activities will strengthen our
      battle to control TB and HIV globally.

PMID- 24025317
TI  - The mitochondrial genome of Protostrongylus rufescens - implications for
      population and systematic studies.
AB  - BACKGROUND: Protostrongylus rufescens is a metastrongyloid nematode of small
      ruminants, such as sheep and goats, causing protostrongylosis. In spite of its
      importance, the ecology and epidemiology of this parasite are not entirely
      understood. In addition, genetic data are scant for P. rufescens and related
      metastrongyloids. METHODS: The mt genome was amplified from a single adult worm
      of P. rufescens (from sheep) by long-PCR, sequenced using 454-technology and
      annotated using bioinformatic tools. Amino acid sequences inferred from
      individual genes of the mt genomes were concatenated and subjected to
      phylogenetic analysis using Bayesian inference. RESULTS: The circular
      mitochondrial genome was 13,619 bp in length and contained two ribosomal RNA, 12
      protein-coding and 22 transfer RNA genes, consistent with nematodes of the order
      Strongylida for which mt genomes have been determined. Phylogenetic analysis of
      the concatenated amino acid sequence data for the 12 mt proteins showed that P.
      rufescens was closely related to Aelurostrongylus abstrusus, Angiostrongylus
      vasorum, Angiostrongylus cantonensis and Angiostrongylus costaricensis.
      CONCLUSIONS: The mt genome determined herein provides a source of markers for
      future investigations of P. rufescens. Molecular tools, employing such mt
      markers, are likely to find applicability in studies of the population biology of
      this parasite and the systematics of lungworms.

PMID- 24025319
TI  - Influence of CB[n] complexation on the quenching of 2,4,6-triphenylpyrylium
      excited states by Fe2+ ions.
AB  - This manuscript focuses on the influence that the addition of Fe(2+) as electron
      donor quencher exerts on the photophysics of 2,4,6-triphenylpyrylium (TP(+))
      depending on the formation or not of supramolecular inclusion complexes with
      cucurbit[n]uril (n: 7 or 8). (1)H-NMR spectroscopy does not provide evidence
      supporting the formation of a ternary TP(+)@CB[n]-Fe(2+) complex. Emission
      quenching studies indicate that the prevalent deactivation mechanism for the
      quenching of TP(+) emission by Fe(2+) is by increasing the ionic strength of the
      solution, with no evidence for the occurrence of dynamic quenching. Laser flash
      photolysis indicates that while the triplet excited state of TP(+) is
      instantaneously quenched by Fe(2+) in the absence of CB[n], formation of the
      TP(+)@CB[n] inclusion complex protects TP(+) triplet excited state from
      quenching, an effect that is more pronounced in the case of CB[8] due to the
      deeper penetration and more complete encapsulation of the heterocyclic pyrylium
      core inside the larger CB[8] capsule. 

PMID- 24025318
TI  - Micromechanical mapping of early osteoarthritic changes in the pericellular
      matrix of human articular cartilage.
AB  - OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease characterized by
      the progressive loss of articular cartilage. While macroscale degradation of the
      cartilage extracellular matrix (ECM) has been extensively studied, microscale
      changes in the chondrocyte pericellular matrix (PCM) and immediate
      microenvironment with OA are not fully understood. The objective of this study
      was to quantify osteoarthritic changes in the micromechanical properties of the
      ECM and PCM of human articular cartilage in situ using atomic force microscopy
      (AFM). METHOD: AFM elastic mapping was performed on cryosections of human
      cartilage harvested from both condyles of macroscopically normal and
      osteoarthritic knee joints. This method was used to test the hypotheses that both
      ECM and PCM regions exhibit a loss of mechanical properties with OA and that the
      size of the PCM is enlarged in OA cartilage as compared to normal tissue.
      RESULTS: Significant decreases were observed in both ECM and PCM moduli of 45%
      and 30%, respectively, on the medial condyle of OA knee joints as compared to
      cartilage from macroscopically normal joints. Enlargement of the PCM, as measured
      biomechanically, was also observed in medial condyle OA cartilage, reflecting the
      underlying distribution of type VI collagen in the region. No significant
      differences were observed in elastic moduli or their spatial distribution on the
      lateral condyle between normal and OA joints. CONCLUSION: Our findings provide
      new evidence of significant site-specific degenerative changes in the chondrocyte
      micromechanical environment with OA.

PMID- 24025320
TI  - Systematic review of the application of the plan-do-study-act method to improve
      quality in healthcare.
AB  - BACKGROUND: Plan-do-study-act (PDSA) cycles provide a structure for iterative
      testing of changes to improve quality of systems. The method is widely accepted
      in healthcare improvement; however there is little overarching evaluation of how
      the method is applied. This paper proposes a theoretical framework for assessing
      the quality of application of PDSA cycles and explores the consistency with which
      the method has been applied in peer-reviewed literature against this framework.
      METHODS: NHS Evidence and Cochrane databases were searched by three independent
      reviewers. Empirical studies were included that reported application of the PDSA
      method in healthcare. Application of PDSA cycles was assessed against key
      features of the method, including documentation characteristics, use of iterative
      cycles, prediction-based testing of change, initial small-scale testing and use
      of data over time. RESULTS: 73 of 409 individual articles identified met the
      inclusion criteria. Of the 73 articles, 47 documented PDSA cycles in sufficient
      detail for full analysis against the whole framework. Many of these studies
      reported application of the PDSA method that failed to accord with primary
      features of the method. Less than 20% (14/73) fully documented the application of
      a sequence of iterative cycles. Furthermore, a lack of adherence to the notion of
      small-scale change is apparent and only 15% (7/47) reported the use of
      quantitative data at monthly or more frequent data intervals to inform
      progression of cycles. DISCUSSION: To progress the development of the science of
      improvement, a greater understanding of the use of improvement methods, including
      PDSA, is essential to draw reliable conclusions about their effectiveness. This
      would be supported by the development of systematic and rigorous standards for
      the application and reporting of PDSAs.

PMID- 24025321
TI  - Changes in the electron paramagnetic resonance spectra of albumin-associated spin
      labeled stearic acid as a diagnostic parameter of colorectal cancer.
AB  - BACKGROUND: With more than 940,000 new colorectal cancer cases worldwide each
      year, there is no better way for colorectal cancer routine screening. The aim of
      this study was to investigate whether the fatty acid binding to albumin is
      detectably and significantly altered in colorectal cancer patients when compared
      with healthy people, in order to find a better way for colorectal cancer
      diagnosis. METHODS: One hundred and forty-one patients operatively treated for
      colorectal cancer were included in the examination, and 180 healthy people were
      also enrolled as controls. Commercial 16-doxyl stearic acid was used as spin
      probe. Serum albumin was analyzed by electron paramagnetic resonance (EPR) with
      spin probe. Discriminant analysis was carried out using the measured EPR spectra
      by SPSS 20.0. RESULTS: Of the original grouped cases, 89.4% were correctly
      classified. Of the cross-validated grouped cases, 86.9% were correctly
      classified. Using Fisher linear discriminant analysis we were able to develop a
      mathematical model allowing for identification of colorectal cancer patients
      based on five values (both relative intensity and peak width) which are obtained
      from the EPR spectrum. CONCLUSIONS: Cancer-associated alterations to albumin can
      be assessed by spin-label EPR. The potential applications for this diagnostic
      technique are significant and represent a cost-effective means for screening
      patients with cancer. Spin probe for diagnosis of colorectal cancer might be a
      useful tool and further studies should take place in order to investigate all
      stages of colorectal cancer patients.

PMID- 24025322
TI  - Helminths and immunological tolerance.
AB  - Current immunosuppression regimens for solid-organ transplantation have shown
      disappointing efficacy in the prevention of chronic allograft rejection and carry
      unacceptable risks including toxicity, neoplasia, and life-threatening infection.
      Achievement of immunological tolerance (long-term antigen unresponsiveness in an
      immunocompetent host) presents the exciting prospect of freedom from
      immunosuppression for transplant recipients. It is now 60 years since the first
      demonstration of immunological tolerance in animal models of transplantation, but
      translation into routine clinical practice remains elusive. Helminth parasites
      may provide novel strategies toward achieving this goal. Helminths are remarkably
      successful parasites: they currently infect more than one quarter of the world's
      population. It is now well established that the parasites' success is the result
      of active immunomodulation of their hosts' immune response. Although this
      primarily secures ongoing survival of the parasites, helminth-induced
      immunomodulation can also have a number of benefits for the host. Significant
      reductions in the prevalence of allergy and autoimmune conditions among helminth
      infected populations are well recognized and there is now a significant body of
      evidence to suggest that harmful immune responses to alloantigens may be
      abrogated as well. Here, we review all existing studies of helminth infection and
      transplantation, explore the mechanisms involved, and discuss possible avenues
      for future translation to clinical practice. 

PMID- 24025323
TI  - Alcohol and substance abuse in solid-organ transplant recipients.
AB  - This review focuses on alcohol and substance abuse in the context of solid-organ
      transplantation. Alcohol and substance abuse are common and may lead to a need
      for solid-organ transplantation and may also contribute to significant physical
      and psychologic problems that impact upon the recipient. Damaging levels of
      alcohol intake can occur in the absence of dependence. Alcohol or substance abuse
      after transplantation is associated with poor medication compliance and this may
      increase risk of graft loss. Intravenous drug use is associated with increased
      risk of infections (especially secondary to opportunistic organisms-bacterial,
      viral, protozoal, and others-and such infections may be more severe in the
      immunosuppressed), but there is only anecdotal evidence that such behavior has a
      worse outcome in transplant recipients. Whereas previous alcohol excess and drug
      use in kidney recipients are both associated with a small but statistically
      significantly increased risk of adverse outcomes (hazard ratio, 1.16-1.56),
      alcohol use within recommended guidelines after transplantation appears safe and
      possibly beneficial. Robust data are lacking for other organs, but those
      available suggest that heart transplantation is safe in individuals with a
      history of alcohol or substance abuse. Health specialists in drug or alcohol
      addiction should carefully screen all potential transplant candidates for these
      conditions, and where there is evidence of dependency or abuse, effective
      psychologic and physical treatment should be offered. Studies have shown that
      interventions such as psychologic intervention have improved alcohol behavior in
      the context of liver transplantation. Although there are no comparable studies
      with other solid-organ recipients, it is reasonable to expect transferable
      outcomes. 

PMID- 24025325
TI  - The Kibble-Zurek mechanism in a subcritical bifurcation.
AB  - We present a study of the freezing dynamics of topological defects in a
      subcritical system by testing the Kibble-Zurek (KZ) mechanism while crossing a
      tri-stable region in a one-dimensional quintic complex Ginzburg-Landau equation.
      The critical exponents of the KZ mechanism and the horizon (KZ-scaling regime)
      are predicted from the quasistatic study, and are in full accordance with the
      quenched study. The correlation length, in the KZ freezing regime, is
      corroborated from the number of topological defects and from the spatial
      correlation function of the order parameter. Furthermore, we characterize the
      dynamics to differentiate three out-of-equilibrium regimes: the adiabatic, the
      impulse and the free relaxation. We show that the impulse regime shares a common
      temporal domain with a fast exponential increase of the order parameter. 

PMID- 24025324
TI  - Elevated CXCL10 (IP-10) in bronchoalveolar lavage fluid is associated with acute
      cellular rejection after human lung transplantation.
AB  - BACKGROUND: CXCL10 (IP-10) is a potent chemoattractant for T cells that has been
      postulated to play a role in infection and acute cellular rejection (ACR) in
      animal models. We measured CXCL10 (IP-10) (and other cytokines previously
      implicated in the pathogenesis of ACR) in the bronchoalveolar lavage (BAL) of
      lung transplant recipients (LTRs) to determine the association between CXCL10 (IP
      10) and ACR in LTRs. METHODS: In a prospective study of 85 LTRs, expression of
      cytokines (tumor necrosis factor, interferon-gamma, interleukin [IL]-6, IL-8, IL
      15, IL-16, IL-17, CXCL10 [IP-10], and MCP-1 [CCL2]) in BAL samples (n=233) from
      patients with episodes of ACR (n=44), infection ("Infect"; n=25), concomitant
      "Infect+ACR" (n=10), and "No Infect and No ACR" (n=154) were analyzed. RESULTS:
      The levels of both CXCL10 (IP-10) and IL-16 were significantly increased in
      histologically proven ACR compared with the "No Infect and No ACR" group (CXCL10
      [IP-10]: 107.0 vs. 31.9 pg/mL [P=0.001] and IL-16: 472.1 vs. 283.01 pg/mL
      [P=0.01]). However, in a linear mixed-effects model, significant association was
      found only between CXCL10 (IP-10) and ACR. A one-log increase of CXCL10 (IP-10)
      was associated with a 40% higher risk of ACR (odds ratio, 1.4; 95% confidence
      interval, 1.12-1.84). CONCLUSION: Higher values of CXCL10 (IP-10) in BAL fluid
      are associated with ACR in LTRs, suggesting a potential mechanistic role in the
      pathogenesis of ACR in LTRs. These results suggest that therapeutic strategies to
      inhibit CXCL10 (IP-10) and or its cognate receptor, CXCR3, warrant investigation
      to prevent and/or treat ACR in clinical lung transplantation.

PMID- 24025326
TI  - Tuning activities of K1.9Na0.1Ta2O6.2H2O nanocrystals in photocatalysis by
      controlling exposed facets.
AB  - Morphology-controlled synthesis of tantalates is a major challenge in the field
      of material science. Herein, an innovative strategy has been developed for
      controllably synthesizing K1.9Na0.1Ta2O6.2H2O (KNTO) nanocrystals shaped as
      octahedra and nanosheets without using any capping agents. The obtained
      nanocrystals show high activity in photocatalytic H2 evolution from CH3OH/H2O
      solution, and their performance closely depends on the exposed facets, in which
      the {111}-facet-bounded nanooctahedra exhibit more than 3 times higher activity
      than the nanosheets dominated with {101} facets. The influence of surface atomic
      structure and electronic band structure on the photocatalytic properties of the
      KNTO nanocrystals is systematically studied. This is the first report for the
      facet controllable synthesis of tantalate materials with highly regular shapes.
      The present approach is anticipated as a general strategy for controllable
      synthesis of tantalate materials and also provides feasibility for rational
      design and activity optimization of shape-controlled photocatalysts for H2
      production. 

PMID- 24025327
TI  - Conformational changes produced by ATP binding to the plasma membrane calcium
      pump.
AB  - The aim of this work was to study the plasma membrane calcium pump (PMCA)
      reaction cycle by characterizing conformational changes associated with calcium,
      ATP, and vanadate binding to purified PMCA. This was accomplished by studying the
      exposure of PMCA to surrounding phospholipids by measuring the incorporation of
      the photoactivatable phosphatidylcholine analog 1-O-hexadecanoyl-2-O-[9-[[[2
      [(125)I]iodo-4-(trifluoromethyl-3H-diazirin-3-yl)benzyl]oxy]carbonyl]nonanoyl]-sn
      glycero-3-phosphocholine to the protein. ATP could bind to the different vanadate
      bound states of the enzyme either in the presence or in the absence of Ca(2+)
      with high apparent affinity. Conformational movements of the ATP binding domain
      were determined using the fluorescent analog 2'(3')-O-(2,4,6
      trinitrophenyl)adenosine 5'-triphosphate. To assess the conformational behavior
      of the Ca(2+) binding domain, we also studied the occlusion of Ca(2+), both in
      the presence and in the absence of ATP and with or without vanadate. Results show
      the existence of occluded species in the presence of vanadate and/or ATP. This
      allowed the development of a model that describes the transport of Ca(2+) and its
      relation with ATP hydrolysis. This is the first approach that uses a
      conformational study to describe the PMCA P-type ATPase reaction cycle, adding
      important features to the classical E1-E2 model devised using kinetics
      methodology only. 

PMID- 24025328
TI  - Toxoplasma transcription factor TgAP2XI-5 regulates the expression of genes
      involved in parasite virulence and host invasion.
AB  - Gene regulation in apicomplexan parasites, a phylum containing important
      protozoan parasites such as Plasmodium and Toxoplasma, is poorly understood. The
      life cycle of Toxoplasma gondii is complex, with multiple proliferation and
      differentiation steps, of which tachyzoite proliferation is the most relevant to
      pathogenesis in humans and animals. Tachyzoites express invasion and virulence
      factors that are crucial for their survival and manipulation of host cell
      functions. The expression of those factors is tightly controlled during the
      tachyzoite cell cycle to permit their correct packaging in newly formed apical
      secretory organelles named micronemes and rhoptries in the daughter cells.
      However, little is known about the factors that control the expression of genes
      encoding the virulence factors present in these parasite-specific secretory
      organelles. We report that the plant-like nuclear factor TgAP2XI-5 targets more
      than 300 gene promoters and actively controls the transcription of these genes.
      Most of these target genes, including those that are essential for parasite
      virulence, showed a peak of expression in the S and M phases of the cell cycle.
      Furthermore, we identified the cis-regulatory element recognized by TgAP2XI-5 and
      demonstrated its ability to actively drive gene transcription. Our results
      demonstrated that TgAP2XI-5 is a novel DNA sequence-specific transcription factor
      associated with promoter activation. TgAP2XI-5 may regulate gene transcription of
      crucial virulence factors in T. gondii. 

PMID- 24025329
TI  - Interleukin-1 and tumor necrosis factor-alpha trigger restriction of hepatitis B
      virus infection via a cytidine deaminase activation-induced cytidine deaminase
      (AID).
AB  - Virus infection is restricted by intracellular immune responses in host cells,
      and this is typically modulated by stimulation of cytokines. The cytokines and
      host factors that determine the host cell restriction against hepatitis B virus
      (HBV) infection are not well understood. We screened 36 cytokines and chemokines
      to determine which were able to reduce the susceptibility of HepaRG cells to HBV
      infection. Here, we found that pretreatment with IL-1beta and TNFalpha remarkably
      reduced the host cell susceptibility to HBV infection. This effect was mediated
      by activation of the NF-kappaB signaling pathway. A cytidine deaminase,
      activation-induced cytidine deaminase (AID), was up-regulated by both IL-1beta
      and TNFalpha in a variety of hepatocyte cell lines and primary human hepatocytes.
      Another deaminase APOBEC3G was not induced by these proinflammatory cytokines.
      Knockdown of AID expression impaired the anti-HBV effect of IL-1beta, and
      overexpression of AID antagonized HBV infection, suggesting that AID was one of
      the responsible factors for the anti-HBV activity of IL-1/TNFalpha. Although AID
      induced hypermutation of HBV DNA, this activity was dispensable for the anti-HBV
      activity. The antiviral effect of IL-1/TNFalpha was also observed on different
      HBV genotypes but not on hepatitis C virus. These results demonstrate that
      proinflammatory cytokines IL-1/TNFalpha trigger a novel antiviral mechanism
      involving AID to regulate host cell permissiveness to HBV infection. 

PMID- 24025330
TI  - Presenilin-1/gamma-secretase controls glutamate release, tyrosine
      phosphorylation, and surface expression of N-methyl-D-aspartate receptor (NMDAR)
      subunit GluN2B.
AB  - Abnormally high concentrations of extracellular glutamate in the brain may cause
      neuronal damage via excitotoxicity. Thus, tight regulation of glutamate release
      is critical to neuronal function and survival. Excitotoxicity is caused mainly by
      overactivation of the extrasynaptic NMDA receptor (NMDAR) and results in specific
      cellular changes, including calcium-induced activation of calpain proteases.
      Here, we report that presenilin-1 (PS1) null mouse cortical neuronal cultures
      have increased amounts of calpain-dependent spectrin breakdown products (SBDPs)
      compared with WT cultures. NMDAR antagonists blocked accumulation of SBDPs,
      suggesting abnormal activation of this receptor in PS1 null cultures.
      Importantly, an increase in SBDPs was detected in cultures of at least 7 days in
      vitro but not in younger cultures. Conditioned medium from PS1 null neuronal
      cultures at 8 days in vitro contained higher levels of glutamate than medium from
      WT cultures and stimulated production of SBDPs when added to WT cultures. Use of
      glutamate reuptake inhibitors indicated that accumulation of this
      neurotransmitter in the media of PS1 null cultures was due to increased rates of
      release. PS1 null neurons showed decreased cell surface expression and
      phosphorylation of the GluN2B subunit of NMDAR, indicating decreased amounts of
      extrasynaptic NMDAR in the absence of PS1. Inhibition of gamma-secretase activity
      in WT neurons caused changes similar to those observed in PS1 null neurons.
      Together, these data indicate that the PS1/gamma-secretase system regulates
      release of glutamate, tyrosine phosphorylation, and surface expression of GluN2B
      containing NMDARs. 

PMID- 24025331
TI  - A crystal structure of the dengue virus non-structural protein 5 (NS5) polymerase
      delineates interdomain amino acid residues that enhance its thermostability and
      de novo initiation activities.
AB  - The dengue virus (DENV) non-structural protein 5 (NS5) comprises an N-terminal
      methyltransferase and a C-terminal RNA-dependent RNA polymerase (RdRp) domain.
      Both enzymatic activities form attractive targets for antiviral development.
      Available crystal structures of NS5 fragments indicate that residues 263-271
      (using the DENV serotype 3 numbering) located between the two globular domains of
      NS5 could be flexible. We observed that the addition of linker residues to the N
      terminal end of the DENV RdRp core domain stabilizes DENV1-4 proteins and
      improves their de novo polymerase initiation activities by enhancing the turnover
      of the RNA and NTP substrates. Mutation studies of linker residues also indicate
      their importance for viral replication. We report the structure at 2.6-A
      resolution of an RdRp fragment from DENV3 spanning residues 265-900 that has
      enhanced catalytic properties compared with the RdRp fragment (residues 272-900)
      reported previously. This new orthorhombic crystal form (space group P21212)
      comprises two polymerases molecules arranged as a dimer around a non
      crystallographic dyad. The enzyme adopts a closed "preinitiation" conformation
      similar to the one that was captured previously in space group C2221 with one
      molecule per asymmetric unit. The structure reveals that residues 269-271
      interact with the RdRp domain and suggests that residues 263-268 of the NS5
      protein from DENV3 are the major contributors to the flexibility between its
      methyltransferase and RdRp domains. Together, these results should inform the
      screening and development of antiviral inhibitors directed against the DENV RdRp.

PMID- 24025332
TI  - Novel details of calsequestrin gel conformation in situ.
AB  - Calsequestrin (CASQ) is the major component of the sarcoplasmic reticulum (SR)
      lumen in skeletal and cardiac muscles. This calcium-binding protein localizes to
      the junctional SR (jSR) cisternae, where it is responsible for the storage of
      large amounts of Ca(2+), whereas it is usually absent, at least in its
      polymerized form, in the free SR. The retention of CASQ inside the jSR is due
      partly to its association with other jSR proteins, such as junctin and triadin,
      and partly to its ability to polymerize, in a high Ca(2+) environment, into an
      intricate gel that holds the protein in place. In this work, we shed some light
      on the still poorly described in situ structure of polymerized CASQ using
      detailed EM images from thin sections, with and without tilting, and from deep
      etched rotary-shadowed replicas. The latter directly illustrate the fundamental
      network nature of polymerized CASQ, revealing repeated nodal points connecting
      short segments of the linear polymer. 

PMID- 24025333
TI  - Structural Insights on the bacteriolytic and self-protection mechanism of
      muramidase effector Tse3 in Pseudomonas aeruginosa.
AB  - The warfare among microbial species as well as between pathogens and hosts is
      fierce, complicated, and continuous. In Pseudomonas aeruginosa, the muramidase
      effector Tse3 (Type VI secretion exported 3) can be injected into the periplasm
      of neighboring bacterial competitors by a Type VI secretion apparatus, eventually
      leading to cell lysis and death. However, P. aeruginosa protects itself from
      lysis by expressing immune protein Tsi3 (Type six secretion immunity 3). Here, we
      report the crystal structure of the Tse3-Tsi3 complex at 1.8 A resolution,
      revealing that Tse3 possesses one open accessible, goose-type lysozyme-like
      domain with peptidoglycan hydrolysis activity. Calcium ions bind specifically in
      the Tse3 active site and are identified to be crucial for its bacteriolytic
      activity. In combination with biochemical studies, the structural basis of self
      protection mechanism of Tsi3 is also elucidated, thus providing an understanding
      and new insights into the effectors of Type VI secretion system. 

PMID- 24025334
TI  - Examination of matrix metalloproteinase-1 in solution: a preference for the pre
      collagenolysis state.
AB  - Catalysis of collagen degradation by matrix metalloproteinase 1 (MMP-1) has been
      proposed to critically rely on flexibility between the catalytic (CAT) and
      hemopexin-like (HPX) domains. A rigorous assessment of the most readily accessed
      conformations in solution is required to explain the onset of substrate
      recognition and collagenolysis. The present study utilized paramagnetic NMR
      spectroscopy and small angle x-ray scattering (SAXS) to calculate the maximum
      occurrence (MO) of MMP-1 conformations. The MMP-1 conformations with large MO
      values (up to 47%) are restricted into a relatively small conformational region.
      All conformations with high MO values differ largely from the closed MMP-1
      structures obtained by x-ray crystallography. The MO of the latter is ~20%, which
      represents the upper limit for the presence of this conformation in the ensemble
      sampled by the protein in solution. In all the high MO conformations, the CAT and
      HPX domains are not in tight contact, and the residues of the HPX domain reported
      to be responsible for the binding to the collagen triple-helix are solvent
      exposed. Thus, overall analysis of the highest MO conformations indicated that
      MMP-1 in solution was poised to interact with collagen and then could readily
      proceed along the steps of collagenolysis.

PMID- 24025336
TI  - Human TEN1 maintains telomere integrity and functions in genome-wide replication
      restart.
AB  - TEN1 is a component of the mammalian CTC1-STN1-TEN1 complex. CTC1 and/or STN1
      functions in telomere duplex replication, C-strand fill-in, and genome-wide
      restart of replication following fork stalling. Here we examine the role of human
      TEN1 and ask whether it also functions as a specialized replication factor. TEN1
      depletion causes an increase in multitelomere fluorescent in situ hybridization
      (FISH) signals similar to that observed after CTC1 or STN1 depletion. However,
      TEN1 depletion also results in increased telomere loss. This loss is not
      accompanied by increased telomere deprotection, recombination, or T-circle
      release. Thus, it appears that both the multiple telomere signals and telomere
      loss stem from problems in telomere duplex replication. TEN1 depletion can also
      affect telomere length, but whether telomeres lengthen or shorten is cell line
      dependent. Like CTC1 and STN1, TEN1 is needed for G-overhang processing.
      Depletion of TEN1 does not effect overhang elongation in mid-S phase, but it
      delays overhang shortening in late S/G2. These results indicate a role for TEN1
      in C-strand fill-in but do not support a direct role in telomerase regulation.
      Finally, TEN1 depletion causes a decrease in genome-wide replication restart
      following fork stalling similar to that observed after STN1 depletion. However,
      anaphase bridge formation is more severe than with CTC1 or STN1 depletion. Our
      findings indicate that TEN1 likely functions in conjunction with CTC1 and STN1 at
      the telomere and elsewhere in the genome. They also raise the possibility that
      TEN1 has additional roles and indicate that TEN1/CTC1-STN1-TEN1 helps solve a
      wide range of challenges to the replication machinery. 

PMID- 24025338
TI  - Impact of autologous dendritic cell-based immunotherapy (AGS-004) on B- and T
      cell subset changes and immune activation in HIV-infected patients receiving
      antiretroviral therapy.
AB  - We previously reported that a combination of antiretroviral therapy with 4
      monthly injections of each patient's own autologous dendritic cells (AGS-004)
      electroporated with CD40 ligand and with HIV RNA antigens obtained from each
      patient's own pre-antiretroviral therapy plasma induced HIV-specific CD8 T-cell
      responses in 10 patients. To assess other AGS-004-induced immune changes, we
      evaluated the modifications in B- and T-cell subsets and the level of immune
      activation in these patients. The proportion of Bm1 naive cells was increased
      along with an augmentation of the proliferation marker Ki67. Memory B-cell
      frequency, CD4 and CD8 T-cell subsets, regulatory T-cell frequency, and CD38/HLA
      DR/PD-1 T-cell activation levels remained unchanged after AGS-004 dendritic cell
      immunotherapy.

PMID- 24025335
TI  - Novel role for p21-activated kinase 2 in thrombin-induced monocyte migration.
AB  - To understand the role of thrombin in inflammation, we tested its effects on
      migration of THP-1 cells, a human monocytic cell line. Thrombin induced THP-1
      cell migration in a dose-dependent manner. Thrombin induced tyrosine
      phosphorylation of Pyk2, Gab1, and p115 RhoGEF, leading to Rac1- and RhoA
      dependent Pak2 activation. Downstream to Pyk2, Gab1 formed a complex with p115
      RhoGEF involving their pleckstrin homology domains. Furthermore, inhibition or
      depletion of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, or Pak2 levels substantially
      attenuated thrombin-induced THP-1 cell F-actin cytoskeletal remodeling and
      migration. Inhibition or depletion of PAR1 also blocked thrombin-induced
      activation of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2, resulting in
      diminished THP-1 cell F-actin cytoskeletal remodeling and migration. Similarly,
      depletion of Galpha12 negated thrombin-induced Pyk2, Gab1, p115 RhoGEF, Rac1,
      RhoA, and Pak2 activation, leading to attenuation of THP-1 cell F-actin
      cytoskeletal remodeling and migration. These novel observations reveal that
      thrombin induces monocyte/macrophage migration via PAR1-Galpha12-dependent Pyk2
      mediated Gab1 and p115 RhoGEF interactions, leading to Rac1- and RhoA-targeted
      Pak2 activation. Thus, these findings provide mechanistic evidence for the role
      of thrombin and its receptor PAR1 in inflammation. 

PMID- 24025339
TI  - Effect of protease inhibitors on steady-state pharmacokinetics of oral
      norethindrone contraception in HIV-infected women.
AB  - OBJECTIVE: Pharmacokinetic interactions exist between combined oral
      contraceptives and protease inhibitors (PI). However, such information is lacking
      for progestin-only oral contraception. We sought to define the steady-state
      pharmacokinetic interaction between norethindrone (NET) and PI in HIV-infected
      women. METHODS AND DESIGN: We conducted an open-label, prospective, nonrandomized
      trial to characterize the steady-state pharmacokinetics of serum NET in HIV
      infected women receiving PI compared with a control group of HIV-infected women
      receiving other noninteracting drugs. After 21 days of 0.35 mg of NET ingestion
      once daily, serial serum samples were obtained at 0, 1, 2, 3, 4, 6, 8, 12, 24,
      48, and 72 hours. The area under the curve between 0 and 72 hours after ingestion
      was calculated by trapezoidal approximation. RESULTS: Thirty-five women were
      enrolled, 2 withdrew. Sixteen women in the PI group and 17 controls completed the
      study. NET half-life and maximum concentration were not significantly different
      between the 2 groups. Minimum concentration of NET was significantly higher in
      the PI group (P = 0.01). The ratio of the geometric mean NET area under the curve
      in the PI group compared with controls was 1.5 (90% confidence interval: 1.21 to
      1.86). NET serum concentrations were significantly higher in HIV-infected women
      taking a PI compared with controls (P = 0.004). CONCLUSIONS: Coadministration of
      PI inhibits NET metabolism as shown by higher serum NET area under the curve
      levels, a surrogate marker for therapeutic contraceptive efficacy. This study
      supports the increased utilization of progestin-only pills in HIV-infected women
      receiving certain PI regimens.

PMID- 24025340
TI  - Systemic endotoxin activity correlates with clot formation: an observational
      study in patients with early systemic inflammation and sepsis.
AB  - INTRODUCTION: Inflammation and coagulation are closely linked, and both can be
      triggered by endotoxin. Thrombelastometry and impedance aggregometry are of
      diagnostic and predictive value in critically ill patients. In this observational
      study we investigated the correlation of endotoxin activity with
      thrombelasometric and aggregometric variables in patients with systemic
      inflammation. METHODS: Based on a daily screening on a tertiary academic surgical
      ICU, patients, as soon as they fulfilled two or more criteria for systemic
      inflammatory response syndrome (SIRS), were included. In whole blood we performed
      endotoxin activity (EA) assay, thrombelastometry (ROTEM(r)) and impendance
      aggregometry (Multiplate(r)). RESULTS: In total, 49 patients were included with a
      broad spread of EA levels of (median (minimum to maximum)) 0.27 (0.01 to 0.72),
      allowing expedient correlative analysis. Clot formation time (CFT) (263 s (60 to
      1,438 s)) and clotting time (CT) (1,008 s (53 to 1,481 s)) showed a significant
      negative correlation with EA level (r = -0.38 (P < 0.005) and r = -0.29 (P <
      0.05)). Positive correlations were found for alpha-angle (50 degrees  (17 to 78
      degrees ), r = 0.40 (P < 0.005)) and maximum clot firmness (MCF) (55 mm (5/76), r
      = 0.27 (P < 0.05)). No significant correlations were found between Lysis Index at
      60 minutes (LI60) and EA levels. There was no correlation between EA level and
      aggregometric values, or classical coagulation parameters. CONCLUSIONS: In
      patients with systemic inflammation, increasing endotoxin concentrations
      correlate with increased clot formation.

PMID- 24025342
TI  - Validation of dilution of plasma samples with phosphate buffered saline to
      eliminate the problem of small volumes associated with children infected with HIV
      1 for viral load testing using Cobas AmpliPrep/COBAS TaqMan HIV-1 test, version
      2.0 (CAP CTM HIV v2.0).
AB  - The sample requirement of 1 mL for the Roche COBAS AmpliPrep/COBAS TaqMan HIV-1
      test, version 2.0 (CAP CTM HIV v2.0) limits its utility in measuring plasma HIV-1
      RNA levels for small volume samples from children infected with HIV-1. Viral load
      monitoring is the standard of care for HIV-1-infected patients on antiretroviral
      therapy in Botswana. The study aimed to validate the dilution of small volume
      samples with phosphate buffered saline (1* PBS) when quantifying HIV-1 RNA in
      patient plasma. HIV RNA concentrations were determined in undiluted and diluted
      pairs of samples comprising panels of quality assessment standards (n=52) as well
      as patient samples (n=325). There was strong correlation (R(2)) of 0.98 and 0.95
      within the dynamic range of the CAP CTM HIV v2.0 test between undiluted and
      diluted samples from quality assessment standards and patients, respectively. The
      difference between viral load measurements of diluted and undiluted pairs of
      quality assessment standards and patient samples using the Altman-Bland test
      showed that the 95% limits of agreement were between -0.40 Log 10 and 0.49 Log
      10. This difference was within the 0.5 Log 10 which is generally considered as
      normal assay variation of plasma RNA levels. Dilution of samples with 1* PBS
      produced comparable viral load measurements to undiluted samples.

PMID- 24025341
TI  - A combination HIV reporter virus system for measuring post-entry event efficiency
      and viral outcome in primary CD4+ T cell subsets.
AB  - Fusion between the viral membrane of human immunodeficiency virus (HIV) and the
      host cell marks the end of the HIV entry process and the beginning of a series of
      post-entry events including uncoating, reverse transcription, integration, and
      viral gene expression. The efficiency of post-entry events can be modulated by
      cellular factors including viral restriction factors and can lead to several
      distinct outcomes: productive, latent, or abortive infection. Understanding host
      and viral proteins impacting post-entry event efficiency and viral outcome is
      critical for strategies to reduce HIV infectivity and to optimize transduction of
      HIV-based gene therapy vectors. Here, we report a combination reporter virus
      system measuring both membrane fusion and viral promoter-driven gene expression.
      This system enables precise determination of unstimulated primary CD4+ T cell
      subsets targeted by HIV, the efficiency of post-entry viral events, and viral
      outcome and is compatible with high-throughput screening and cell-sorting
      methods. 

PMID- 24025343
TI  - Development of a loop-mediated isothermal amplification assay for rapid detection
      of iridovirus in the Chinese giant salamander.
AB  - The Chinese giant salamander (Andrias davidianus) iridovirus (GSIV) is an
      emerging infectious pathogen responsible for severe hemorrhagic disease and high
      mortality in cultured Chinese giant salamanders. A loop-mediated isothermal
      amplification (LAMP) assay based on the major caspid protein (MCP) gene has been
      developed to detect this virus. Primer pairs for the LAMP assay were designed
      based on the GSIV MCP gene sequence. Amplification results indicate that under
      optimized conditions the LAMP assay has the ability to specifically detect the
      virus in both diseased animals and infected epithelioma papilloma cyprinid (EPC)
      cells. The assay was shown to be 10-fold more sensitive than nested PCR and was
      able to detect concentrations of 10(-9) (approximately 0.01 pg/MUL). The LAMP
      assay is relatively easy to perform in situ and the amplification products can be
      observed directly under UV light or via staining with SYBR Green I. The LAMP
      assay is also rapid and cost-effective. This study establishes the use of a LAMP
      assay for rapid detection of GSIV, which is a novel and important tool for the
      diagnosis of GSIV infection in laboratory or farmed Chinese giant salamanders.

PMID- 24025344
TI  - Rapid detection of Grapevine leafroll-associated virus type 3 using a reverse
      transcription loop-mediated amplification method.
AB  - Grapevine leafroll disease (GLD) is the most important disease of Grapevines in
      South Africa. Grapevine leafroll-associated virus type 3 (GLRaV-3) has a close
      association with the disease and is prevalent in South African vineyards. GLD can
      be controlled using a combination of virus-free planting material, systemic
      insecticides to control vector populations and removal of infected vines by
      roguing. Infected vines are identified each autumn using either symptom display
      (in red cultivars) or ELISA (in white cultivars). While ELISA is a simple,
      reliable means of testing for GLRaV-3, it is time consuming, laborious and
      insensitive and a quicker, more sensitive method of detecting GLRaV-3 in the
      field is needed. A single-tube one-step reverse transcription (RT) loop-mediated
      isothermal amplification (LAMP) assay combined with a simple RNA extraction
      protocol was developed for the rapid and easy detection of GLRaV-3. Hydroxy
      napthol blue was included as an indicator and under isothermal conditions at 60 
      degrees C the target viral gene could be amplified in under 2h and positive
      results could be easily seen by examining the colour change from violet to sky
      blue. Using this method, 50 samples could be also pooled together with a single
      positive sample still being detected. A direct comparison of ELISA, nested PCR
      and RT-LAMP showed that RT-LAMP is as sensitive as nested PCR and could be
      performed in a much shorter time with less equipment. This assay is may be a
      possible alternative to ELISA for the detection of GLRaV-3 in the field.

PMID- 24025345
TI  - Lingual orthodontics for children and adolescents: improvement of the indirect
      bonding protocol.
AB  - INTRODUCTION: Demineralization of the dental enamel is a finding associated with
      fixed orthodontic treatment. When an indirect bonding procedure is used in
      children and adolescents the area beneath the bracket base may be affected. AIM:
      To evaluate if the addition of an extra layer of a hydrophilic resin, to a
      conventional indirect bonding protocol, can reduce the incidence of
      demineralization beneath the bracket base. METHODS: 40 patients under 18 years of
      age were treated with completely customized lingual appliances. Two different
      bonding protocols were used either with or without the application of an
      additional layer of hydrophilic resin. Demineralization beneath the bracket base,
      after de-bonding, was evaluated by standardized intra-oral photographs. RESULTS:
      The addition of an extra layer of a hydrophilic resin helps to reduce the number
      of demineralized areas beneath the bracket bases significantly (three times
      less). The severity of the few remaining defects were minor and without any
      clinical consequence. CONCLUSION: When bonding a completely customized lingual
      appliance in children and adolescents, an extra layer of a hydrophilic resin
      should be added to the teeth.

PMID- 24025346
TI  - Persistent bloody diarrhoea without fever associated with diffusely adherent
      Escherichia coli in a young child.
AB  - Diffusely adherent Escherichia coli (DAEC) is thought to cause diarrhoea in
      children, and so too are other diarrhoeagenic E. coli (DEC); however, the
      evidence base is inconclusive. DEC pathotypes are differentiated on the basis of
      their pathogenic features, and thus cannot be quickly identified on selective
      culture media. Molecular techniques, not readily available in most clinical
      laboratories, are required to differentiate DEC strains from non-pathogenic E.
      coli in the stool flora. We report a case of persistent bloody diarrhoea, without
      fever, in a previously healthy 21-month infant from whom we isolated five DAEC
      strains. The child's stools movements were loose, with gross blood and mucus;
      fresh mount analysis revealed numerous faecal leukocytes and erythrocytes.
      Response to antimicrobial treatment with trimethoprim-sulfamethoxazole was poor
      despite susceptibility in vitro. Although the patient improved with azithromycin,
      blood was present in the patient's stools for over 30 days. The severe diarrhoea
      in this patient might be explained by the fact that these DAEC isolates harboured
      a siderophore receptor, which allows the bacteria to use iron derived from haem
      compounds that promote its multiplication. The isolates also induced in vitro
      secretion of several immunomodulatory cytokines that may account for the
      patient's loose stools and faecal leukocytes. DAEC may play a greater role than
      suspected in afebrile children with bloody diarrhoea. 

PMID- 24025347
TI  - Characterization of heat-shock proteins in Escherichia coli strains under thermal
      stress in vitro.
AB  - The aim of this study was to evaluate the effect of heat stress in in vitro
      conditions on the induction of heat-shock protein (Hsp)70 by Escherichia coli
      cells, and to determine the localization of Hsps in cell fractions. The material
      consisted of wild strains of E. coli isolated from the digestive tract of calves,
      suspended in an exponential-phase culture and subjected to 41.5  degrees C for 2
      h. Individual fractions were analysed by SDS-PAGE and two-dimensional
      electrophoresis. Western blotting with mouse anti-Hsp70 and anti-Hsp60 mAbs was
      used to identify the proteins. Electrophoretic analysis of the heat-treated cells
      detected Hsp70 in all three fractions, cytoplasmic, periplasmic and membrane,
      which was confirmed by Western blotting. The proteins obtained had diverse
      localizations in the pH gradient in two-dimensional electrophoresis, which may
      indicate changes in their conformation and physical properties leading to
      stabilization and protection of intracellular structures in stress conditions.
      The presence of these Hsps in different cell fractions indicates a very strong
      protective adaptation in the bacteria in unfavourable conditions, which is
      critical for the organism infected by them. 

PMID- 24025348
TI  - Molecular epidemiology and serogroup 6 capsular gene evolution of pneumococcal
      carriage in a Japanese birth cohort study.
AB  - Antibiotic resistance in Streptococcus pneumoniae is a major concern worldwide.
      However, it is unclear whether resistance is associated with only a few highly
      prevalent clones or numerous and diverse clones. We monitored 349 healthy
      children and obtained nasopharyngeal cultures at five time points coinciding with
      health check-ups (4, 7, 10, 18 and 36 months) between 2008 and 2012. A total of
      497 S. pneumoniae isolates from 257 healthy children were characterized using
      capsular serotyping, multilocus sequence typing and antibiotic resistance
      genotyping (ermB, mefA/E and pbp mutations). Among these isolates, 25 serotypes
      and 66 sequence types (STs) were found, including 24 new STs with 11 new alleles.
      Although resistance was present in a variety of ST clones, most of the clones
      (57/66, 86.4 %) had one specific resistant or susceptible genotype. Of 233
      phenotypically penicillin-non-susceptible isolates, 196 (84.1 %) belonged to only
      six clones, comprising ST90(6B), ST236(19F), ST242(23F), ST3787(6A), ST1437(23F)
      and ST338(23A) and their variants. We concluded that drug-resistant S. pneumoniae
      is associated with a limited number of highly prevalent clones that are capable
      of adapting to the community setting. Furthermore, we analysed the capsular gene
      evolution in serogroup 6. The strain ST2924(6D) was probably the result of
      recombination of a 3563 bp fragment of the capsule locus acquired by an
      ST2924(6C) strain from an ST90(6B) or ST2924(6B) strain. Compared with previous
      studies, our results showed a different recombination site (wciN and wzx) and a
      different cps profile (8-7-11), indicating that serogroup 6 strains have multiple
      sites for cps recombination as a mechanism of vaccine escape. 

PMID- 24025349
TI  - Influence of macrosocial policies on women's health and gender inequalities in
      health.
AB  - Gender inequalities in health have been widely described, but few studies have
      examined the upstream sources of these inequalities in health. The objectives of
      this review are 1) to identify empirical papers that assessed the effect of
      gender equality policies on gender inequalities in health or on women's health by
      using between-country (or administrative units within a country) comparisons and
      2) to provide an example of published evidence on the effects of a specific
      policy (parental leave) on women's health. We conducted a literature search
      covering the period from 1970 to 2012, using several bibliographical databases.
      We assessed 1,238 abstracts and selected 19 papers that considered gender
      equality policies, compared several countries or different states in 1 country,
      and analyzed at least 1 health outcome among women or compared between genders.
      To illustrate specific policy effects, we also selected articles that assessed
      associations between parental leave and women's health. Our review partially
      supports the hypothesis that Nordic social democratic welfare regimes and dual
      earner family models best promote women's health. Meanwhile, enforcement of
      reproductive policies, mainly studied across US states, is associated with better
      mental health outcomes, although less with other outcomes. Longer paid maternity
      leave was also generally associated with better mental health and longer duration
      of breastfeeding. 

PMID- 24025351
TI  - Low birth weight in the offspring of women with anorexia nervosa.
AB  - A growing body of literature has investigated the association between maternal
      anorexia nervosa and pregnancy outcomes. Infant low birth weight is associated
      with a number of neurodevelopmental and physical sequelae; however, consistent
      results on its association with maternal anorexia nervosa are scant. Therefore, a
      systematic review and meta-analysis of the existing literature were undertaken.
      PubMed, Embase, and PsychInfo were searched for studies comparing the mean birth
      weight of babies delivered by mothers with (a history of) anorexia nervosa
      against those of healthy mothers. Studies were excluded from the meta-analysis if
      not presenting data from an unexposed comparison group and if using multiple
      eating disorders as exposure without presenting individual results. Fourteen
      studies were included in the systematic review and 9 in the meta-analysis,
      undertaken between 1999 and 2012 in Denmark, the Netherlands, New Zealand,
      Norway, Sweden, and the United Kingdom. Birth weights were standardized by
      dividing the difference in mean birth weight by the pooled standard deviation
      (equivalent to Cohen's d). Results showed a standardized mean difference of -0.19
      kg (95% confidence interval: -0.25, -0.15; P = 0.01) in the birth weight of
      children of mothers with anorexia nervosa, and some bias in favor of papers
      presenting lower birth weight results for exposed mothers was detected. However,
      the small power of the analysis due to the small number of available studies and,
      thus, chance could partially account for this result. Our results confirm that
      maternal anorexia nervosa predicts lower birth weight and, despite some
      limitations, they have important clinical implications for prevention of adverse
      child outcomes. 

PMID- 24025352
TI  - Analysis of the multiferroicity in the hexagonal manganite YMnO3.
AB  - We performed magnetic and ferroelectric measurements, associated with Landau
      theory and symmetry analysis, in order to clarify the situation of the YMnO3
      system, a classical example of type I multiferroics. We found that the only
      magnetic group compatible with all experimental data (neutron scattering,
      magnetization, polarization, dielectric constant, second harmonic generation) is
      the P6'(3) group. In this group a small ferromagnetic component along c is
      induced by the Dzyaloshinskii-Moriya interaction, and observed here in
      magnetization measurements. We found that the ferromagnetic and antiferromagnetic
      components can only be switched simultaneously, while the magnetic orders are
      functions of the polarization square and therefore insensitive to its sign.

PMID- 24025350
TI  - Pregnancy characteristics and women's future cardiovascular health: an underused
      opportunity to improve women's health?
AB  - Growing evidence indicates that women with a history of common pregnancy
      complications, including fetal growth restriction and preterm delivery (often
      combined as low birth weight), hypertensive disorders of pregnancy, and
      gestational diabetes, are at increased risk for cardiovascular disease later in
      life. The purpose of this paper was to review the associations of parity and
      these 4 pregnancy complications with cardiovascular morbidity and mortality; to
      review the role of cardiovascular risk factors before, during, and after
      pregnancy complications in explaining these associations; and to explore the
      implications of this emerging science for new research and policy. We
      systematically searched for relevant cohort and case-control studies in Medline
      through December 2012 and used citation searches for already published reviews to
      identify new studies. The findings of this review suggest consistent and often
      strong associations of pregnancy complications with latent and future
      cardiovascular disease. Many pregnancy complications appear to be preceded by
      subclinical vascular and metabolic dysfunction, suggesting that the complications
      may be useful markers of latent high-risk cardiovascular trajectories. With
      further replication research, these findings would support the utility of these
      prevalent pregnancy complications in identifying high-risk women for screening,
      prevention, and treatment of cardiovascular disease, the leading cause of
      morbidity and mortality among women. 

PMID- 24025353
TI  - The mechanism of necroptosis in normal and cancer cells.
AB  - Programmed cell death is a basic cellular process that is critical to maintain
      tissue homeostasis. Besides apoptosis, necroptosis has more recently been
      discovered as another form of regulated cell death. Necroptosis plays a pivotal
      role during normal development and has also been implicated in the pathogenesis
      of a variety of human diseases. The control of necroptosis by defined signal
      transduction pathways offers the opportunity to target this cellular process for
      therapeutic purposes. For example, in cancer necroptosis is often impaired during
      tumorigenesis and can be engaged by targeted pharmacological approaches. Further
      insights into the signaling networks involved in the regulation of necroptosis
      will likely have important implications for the exploitation of this form of
      programmed cell death for the diagnosis or treatment of many diseases. 

PMID- 24025354
TI  - Targeting the ERK pathway reduces liver metastasis of Smad4-inactivated
      colorectal cancer.
AB  - Transforming growth factor beta (TGF-beta)/Smad signaling is involved in
      colorectal carcinoma (CRC) development and progression. The frequent loss of
      SMAD4 is associated with liver metastasis and poor prognosis of CRC, but the
      underlying mechanism remains elusive. This study aimed to elucidate the role of
      Smad-independent TGF-beta signaling in CRC metastasis. Immunohistochemistry
      showed that Smad4 level was negatively correlated with TNM stage and phospho-ERK
      level in human CRCs and liver metastasis samples. Knockdown of Smad4 in CT26 and
      HCT116 cells activated ERK pathway, altered the expression of MMP2 and COX-2,
      promoted cell motility, migration, and invasion in vitro, enhanced metastasis,
      and shortened the survival of metastatic tumor-bearing mice. MEK inhibitor U0126
      and GSK1120212 inhibited the motility, migration, and invasion of Smad4 knockdown
      cells, inhibited metastasis, and prolonged the survival of metastatic tumor
      bearing mice. Furthermore, MEK inhibitor could reverse the changes of phospho
      ERK, MMP2, and COX-2 levels. In conclusion, our results indicate that ERK pathway
      plays a key oncogenic role in CRC with SMAD4 inactivation mutations, and
      implicate ERK as a potential therapeutic target for CRC liver metastasis. 

PMID- 24025355
TI  - Berberine enhances radiosensitivity of esophageal squamous cancer by targeting
      HIF-1alpha in vitro and in vivo.
AB  - Radiation therapy is an important treatment approach for esophageal squamous cell
      carcinoma (ESCC). However, how to promote radiation sensitivity in ESCC remains a
      challenge. This study aimed to evaluate the effects of berberine, a common used
      Chinese medicine, on the radiosensitivity of ESCC. ECSS cell line ECA109 and TE13
      were subjected to hypoxia and/or ionizing radiation (IR), in the presence or
      absence of berberine treatment. Cell growth and survival, and apoptosis were
      evaluated. In addition, ECA109 cells were xenografted into nude mice and
      subjected to IR and/or berberine treatment. The expression of HIF-1alpha and VEGF
      was detected by western blot and immunohistochemical analysis. Our results showed
      that berberine increased radiosensitivity of ESCC cells and xenografts, and this
      was associated with the inhibition of HIF-1alpha and VEGF expression. These data
      suggest that berberine may be a potential radiotherapy sensitization drugs due to
      its significant anti-hypoxia activity. 

PMID- 24025356
TI  - ERK plays the baddie (again).
AB  - It has been known for many years that elevated signaling by the ERK1/2 pathway is
      frequently associated with the growth and survival of many tumor cell types under
      a variety of normal and stressful conditions, including the response of cells to
      other cancer interventional therapeutic strategies e.g., references 1-4. There
      is, however, a modest significant literature showing that enhanced ERK1/2
      signaling can also cause tumor cell death e.g., references 5-8. The role of
      ERK1/2 signaling is clearly complex, for example as shown by the Koumenis group
      where inhibition of radiation-induced ERK1/2 signaling caused radiosensitization,
      whereas inhibition of curcumin-hyper-stimulated ERK1/2 signaling reduced
      radiosensitivity. 7 Presumably this Janus-faced behavior of the ERK1/2 pathway in
      terms of cell survival regulation will depend upon the tumor cell type, the
      intensity of ERK1/2 stimulation, and the molecular intervention/drug being used.

PMID- 24025357
TI  - Prostate cancer progression attributed to autonomic nerve development: potential
      for therapeutic prevention of localized and metastatic disease.
AB  - In a study recently published in Science, Magnon et al. show that both the
      sympathetic and parasympathetic components of the autonomic nervous system play
      an integral part in the development and dissemination of prostate cancer (PCa).
      Inhibition of the sympathetic nervous system (SNS) and disruption of the
      adrenergic receptors, specifically Ardbeta 2, resulted in the prevention of
      primary PCa tumor development in mice. The authors found that inhibition of the
      SNS is only successful in preventing murine tumor development if completed early
      enough, and the parasympathetic nervous system (PNS) predominates in later stages
      of PCa. Inhibition of the PNS by way of the cholinergic receptor, muscarinic 1
      (Chrm1), caused mice to develop less metastases to the pelvic lymph nodes,
      intestines, and bones. A PCa progression scheme has been outlined where initial
      tumor engraftment is controlled by the SNS but then becomes less prominent than
      the PNS, which promotes metastasis. The investigators showed the dependence of
      the autonomic nervous system on development of PCa and present opportunities for
      prevention; further studies are needed to confirm these results in humans. 

PMID- 24025358
TI  - Omega-3 polyunsaturated fatty acid promotes the inhibition of glycolytic enzymes
      and mTOR signaling by regulating the tumor suppressor LKB1.
AB  - The omega-3 polyunsaturated fatty acids (omega3PUFAs) are a class of lipids
      biologically effective for the treatment of inflammatory disorders,
      cardiovascular disease and cancer. Patients consuming a high dietary intake of
      omega3PUFAs have shown a low incidence of metabolic disorders, including cancer.
      Although the effects of omega3PUFAs intake was shown to be involved in the
      prevention and treatment of these diseases, the underlying molecular mechanisms
      involved are not well understood. Here, we show that omega3PUFA, docosahexaenoic
      acid (DHA) enhanced the tumor suppressor function of LKB1. We observed that when
      LKB1 expressing cells are treated with DHA, there is an increase in LKB1 activity
      leading to phosphorylation of AMPK and inhibition of mTOR signaling. Abrogation
      of LKB1 in MCF-7 cells by siRNA reversed this phenotype. Furthermore, cellular
      metabolism was altered and ATP levels were reduced in response to DHA treatment,
      which was further attenuated in cells expressing LKB1. More importantly, in
      mammary epithelial cells expressing LKB1, the rate of glycolysis was decreased as
      a result of diminished expression of glycolytic enzymes. Functionally, these
      events lead to a decrease in the migration potential of these cells. Overall, our
      discovery shows for the first time that LKB1 function is enhanced in response to
      omega3PUFA treatment, thereby resulting in the regulation of cell metabolism. 

PMID- 24025359
TI  - Combining histone deacetylase inhibitors with MDA-7/IL-24 enhances killing of
      renal carcinoma cells.
AB  - In the present study we show that histone deacetylase inhibitors (HDACIs) enhance
      the anti-tumor effects of melanoma differentiation associated gene-7/interleukin
      24 (mda- 7/IL-24) in human renal carcinoma cells. Similar data were obtained in
      other GU tumor cells. Combination of these two agents resulted in increased
      autophagy that was dependent on expression of ceramide synthase 6, with HDACIs
      enhancing MDA-7/IL-24 toxicity by increasing generation of ROS and Ca (2+). Knock
      down of CD95 protected cells from HDACI and MDA-7/IL-24 lethality. Sorafenib
      treatment further enhanced (HDACI + MDA-7/IL-24) lethality. Anoikis resistant
      renal carcinoma cells were more sensitive to MDA-7/IL-24 that correlated with
      elevated SRC activity and tyrosine phosphorylation of CD95. We employed a
      recently constructed serotype 5/3 adenovirus, which is more effective than a
      serotype 5 virus in delivering mda- 7/IL-24 to renal carcinoma cells and which
      conditionally replicates (CR) in tumor cells expressing MDA-7/IL-24 by virtue of
      placing the adenoviral E1A gene under the control of the cancer-specific promoter
      progression elevated gene-3 (Ad.5/3-PEG-E1A-mda-7; CRAd.5/3-mda-7, Ad.5/3-CTV),
      to define efficacy in renal carcinoma cells. Ad.5/3-CTV decreased the growth of
      renal carcinoma tumors to a significantly greater extent than did a non
      replicative virus Ad.5/3-mda-7. In contralateral uninfected renal carcinoma
      tumors Ad.5/3-CTV also decreased the growth of tumors to a greater extent than
      did Ad.5/3-mda-7. In summation, our data demonstrates that HDACIs enhance MDA
      7/IL-24-mediated toxicity and tumor specific adenoviral delivery and viral
      replication of mda-7/IL-24 is an effective pre-clinical renal carcinoma
      therapeutic. 

PMID- 24025360
TI  - The antitumor activity of the human FOLR1-specific monoclonal antibody,
      farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent
      cellular cytotoxicity.
AB  - Because of its high mortality rate, ovarian cancer is a leading cause of death
      among women and a highly unmet medical need. New therapeutic agents that are
      effective and well tolerated are needed and cancer antigen-specific monoclonal
      antibodies that have direct pharmacologic effects or can stimulate immunological
      responses represent a promising class of agents for the treatment of this
      disease. The human folate receptor alpha (FOLR1), which is overexpressed in
      ovarian cancer but largely absent in normal tissues, appears to play a role in
      the transformed phenotype in ovarian cancer, cisplatin sensitivity, and growth in
      depleted folate conditions and therefore has potential as a target for passive
      immunotherapy. The anti-FOLR1 monoclonal antibody MORAb-003 (farletuzumab) was
      previously shown to elicit antibody dependent cellular cytotoxicity (ADCC) and
      inhibit tumor growth of human tumor xenografts in nude mice. Because of its
      promising preclinical profile, farletuzumab has been evaluated in clinical trials
      as a potential therapeutic agent for ovarian cancer. In this report, we
      demonstrated that farletuzumab's antitumor effect against an experimental model
      of ovarian cancer is mediated by its ADCC activity. 

PMID- 24025361
TI  - A novel synthetic derivative of the natural product berbamine inhibits cell
      viability and induces apoptosis of human osteosarcoma cells, associated with
      activation of JNK/AP-1 signaling.
AB  - Osteosarcoma is the most common primary bone tumor in children and adolescents.
      There is a critical need to find more potent drugs for patients with metastatic
      or recurrent disease. Berbamine (BBM) is a natural compound derived from the
      Berberis amurensis plants. BBM and its derivatives have been shown to have
      antitumor effects in several cancers. Here, we report that a novel synthetic
      berbamine derivative, BBMD3, inhibits cell viability and induces apoptosis of
      G292, KHOS, and MG-63 human osteosarcoma cells. Induction of apoptosis in these
      tumor cells depends on activation of caspase-3 and cleavage of poly(ADP-ribose)
      polymerase (PARP). Since pan-caspase inhibitor (Z-VAD-FMK) and caspase-9
      inhibitor (Z-LEHD-FMK) could block the cleavage of PARP, the apoptosis induced by
      BBMD3 is through intrinsic signaling pathway. BBMD3 increased phosphorylation of
      c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK), resulting
      in increase of phosphorylated c-Jun and total c-Fos, the major components of
      transcriptional factor AP-1. JNK inhibitor could partially suppress antitumor
      effect of BBMD3 on osteosarcoma cells. BBMD3 increased the production of reactive
      oxygen species (ROS) and ROS scavenger, N-acetylcysteine (NAC), could block the
      phosphorylation of JNK and c-Jun induced by BBMD3. BBMD3 increased the expression
      of the pro-apototic gene Bad, associated with apoptosis induction. Finally, BBMD3
      also decreased the expression of cyclin D1 and D2, the positive cell cycle
      regulators, which is correlated with growth inhibition in osteosarcoma cells.
      Collectively, these findings indicate that BBMD3 is a potentially promising drug
      for the treatment of human osteosarcoma. 

PMID- 24025362
TI  - Oncolytic adenovirus encoding tumor necrosis factor-related apoptosis inducing
      ligand (TRAIL) inhibits the growth and metastasis of triple-negative breast
      cancer.
AB  - Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising
      cancer therapeutic target due to its selective apoptosis-inducing effect in
      cancer cells. To efficiently deliver TRAIL to the tumor cells, an oncolytic
      adenovirus (p55-hTERT-HRE-TRAIL) carrying the TRAIL coding sequence was
      constructed. In the present study, we aimed to investigate the effect of p55
      hTERT-HRE-TRAIL on the growth and metastasis of triple-negative breast cancer
      (TNBC). We observed that infection of the recombinant adenovirus resulted in
      expression of TRAIL and massive cell death in a TNBC cell line MDA-MB-231. This
      effect is much weaker in MCF-10A, which is a normal breast cell line.
      Administration of P55-HTERT-HRE-TRAIL significantly reduced orthotopic breast
      tumor growth and extended survival in a metastatic model. Our results suggest the
      oncolytic adenovirus armed with P55-HTERT-HRE-TRAIL, which exhibited enhanced
      anti-tumor activity and improved survival, is a promising candidate for
      virotherapy of TNBC. 

PMID- 24025363
TI  - Who enrolls in the Medicare Part D prescription drug benefit program? Medication
      use among patients with heart failure.
AB  - BACKGROUND: Dispensing data from Medicare Part D standalone prescription drug
      plans are now available, but characteristics of enrollees with heart failure have
      not been well described. METHODS AND RESULTS: We identified 81 874 patients with
      prevalent heart failure as of January 1, 2010, in a nationally representative 5%
      sample of Medicare beneficiaries. We classified patients according to enrollment
      in a Medicare Part D plan as of January 1, 2010. Demographic characteristics,
      comorbid conditions, and prescriptions were compared by enrollment status. A
      total of 49 252 (60.2%) were enrolled in a Medicare Part D plan as of January 1.
      Enrollees were more often women, black, and of lower socioeconomic status.
      Enrollees with heart failure more often filled prescriptions for loop diuretics
      than angiotensin-converting enzyme inhibitors or angiotensin receptor blockers,
      beta-blockers, or aldosterone antagonists. During the first 4 months of 2010,
      5444 (12.3%) reached the coverage gap, and 566 (1.3%) required catastrophic
      coverage beyond the gap. CONCLUSIONS: Medicare beneficiaries with heart failure
      differ significantly according to enrollment in Part D prescription drug plans
      and represent a population underrepresented in clinical efficacy trials. Many
      face the coverage gap, and few select Medicare Part D plans that provide coverage
      during the gap. Linking Medicare Part D event data with clinical registries could
      help to determine whether eligible enrollees are undertreated for heart failure.

PMID- 24025364
TI  - Men having sex with men serosorting with casual partners: who, how much, and what
      risk factors in Switzerland, 2007-2009.
AB  - BACKGROUND: Serosorting is practiced by men who have sex with men (MSM) to reduce
      human immunodeficiency virus (HIV) transmission. This study evaluates the
      prevalence of serosorting with casual partners, and analyses the characteristics
      and estimated numbers of serosorters in Switzerland 2007-2009. METHODS: Data were
      extracted from cross-sectional surveys conducted in 2007 and 2009 among self
      selected MSM recruited online, through gay newspapers, and through gay
      organizations. Nested models were fitted to ascertain the appropriateness of
      pooling the datasets. Multiple logistic regression analysis was performed on
      pooled data to determine the association between serosorting and demographic,
      lifestyle-related, and health-related factors. Extrapolations were performed by
      applying proportions of various types of serosorters to Swiss population data
      collected in 2007. RESULTS: A significant and stable number of MSM (approximately
      39% in 2007 and 2009) intentionally engage in serosorting with casual partners in
      Switzerland. Variables significantly associated with serosorting were: gay
      organization membership (aOR = 1.67), frequent internet use for sexual encounters
      (aOR = 1.71), having had a sexually transmitted infection (STI) at any time in
      the past 12 months (aOR = 1.70), HIV-positive status (aOR = 0.52), regularly
      frequenting sex-on-premises venues (aOR = 0.42), and unprotected anal intercourse
      (UAI) with partners of different or unknown HIV status in the past 12 months (aOR
      = 0.22). Approximately one-fifth of serosorters declared HIV negativity without
      being tested in the past 12 months; 15.8% reported not knowing their own HIV
      status. CONCLUSION: The particular risk profile of serosorters having UAI with
      casual partners (multiple partners, STI history, and inadequate testing
      frequency) requires specific preventive interventions tailored to HIV status.

PMID- 24025366
TI  - Essential key indicators for disaster medical response suggested to be included
      in a national uniform protocol for documentation of major incidents: a Delphi
      study.
AB  - BACKGROUND: Registration of data from a major incident or disaster serves several
      purposes such as to record data for evaluation of response as well as for
      research. Data needed can often be retrieved after an incident while other must
      be recorded during the incident. There is a need for a consensus on what is
      essential to record from a disaster response. The aim of this study was to
      identify key indicators essential for initial disaster medical response
      registration. By this is meant nationally accepted processes involved, from the
      time of the emergency call to the emergency medical communication centre until
      medical care is provided at the emergency department. METHODS: A three round
      Delphi study was conducted. Thirty experts with a broad knowledge in disaster and
      emergency response and medical management were invited. In this study we
      estimated 30 experts to be approximately one third of the number in Sweden
      eligible for recruitment. Process, structure and outcome indicators for the
      initial disaster medical response were identified. These were based on previous
      research and expressed as statements and were grouped into eight categories, and
      presented to the panel of experts. The experts were instructed to score each
      statement, using a five point Likert scale, and were also invited to include
      additional statements. Statements reaching a predefined consensus level of 80%
      were considered as essential to register. RESULTS: In total 97 statements were
      generated, 77 statements reached consensus. The 77 statements covered parts of
      all relevant aspects involved in the initial disaster medical response. The 20
      indicators that did not reach consensus mostly concerned patient related times in
      hospital, types of support systems and security for health care staff.
      CONCLUSIONS: The Delphi technique can be used for reaching consensus of data,
      comprising process, structure and outcome indicators, identified as essential for
      recording from major incidents and disasters.

PMID- 24025365
TI  - The roles of microRNAs on tuberculosis infection: meaning or myth?
AB  - The central proteins for protection against tuberculosis are attributed to
      interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1beta,
      while IL-10 primarily suppresses anti-mycobacterial responses. Several studies
      found alteration of expression profile of genes involved in anti-mycobacterial
      responses in macrophages and natural killer (NK) cells from active and latent
      tuberculosis and from tuberculosis and healthy controls. This alteration of
      cellular composition might be regulated by microRNAs (miRNAs). Albeit only 1% of
      the genomic transcripts in mammalian cells encode miRNA, they are predicted to
      control the activity of more than 60% of all protein-coding genes and they have a
      huge influence in pathogenesis theory, diagnosis and treatment approach to some
      diseases. Several miRNAs have been found to regulate T cell differentiation and
      function and have critical role in regulating the innate function of macrophages,
      dendritic cells and NK cells. Here, we have reviewed the role of miRNAs
      implicated in tuberculosis infection, especially related to their new roles in
      the molecular pathology of tuberculosis immunology and as new targets for future
      tuberculosis diagnostics. 

PMID- 24025368
TI  - Dynamic formation of zeolite synthesized from fly ash by alkaline hydrothermal
      conversion.
AB  - This study was designed to characterize the dynamic formation of zeolite
      synthesized from fly ash (ZFA) and to identify the zeolitization mechanisms
      during a 160-h-long hydrothermal alkaline conversion at 95 degrees C by using fly
      ash (FA) samples collected from four typical thermoelectric power plants in
      China, with the purpose of improving ZFA quality. The process of synthesizing ZFA
      can be fundamentally divided into five stages: induction stage (0-0.5 h),
      accelerating dissolution stage (0.5-12 h), nucleation and/or crystallization
      stage (12-24 h), crystal growth stage (24-72 h) and crystal transformation stage
      (72-160 h). The crystal growth stage determined the quality of zeolite
      crystallization, coupled with functions of re-assembling the silicon-aluminium
      tetrahedral network and developing submicro- and/or nanometer microstructure. A
      48-h-long hydrothermal conversion generated ZFAs that had a greater specific
      surface area (26.0-89.4 times) and cation exchange capacity (29.6-71.0 times)
      than FA, which successfully sequestrated 41-95% of ammonium and 75-98% of
      phosphate from swine manure. However, over-reaction resulted in more stable
      hydroxysodalite and/or sodalite, surface agglomeration and cracking, and energy
      wasting. This work suggests that the reuse of recycled synthesis materials should
      occur during the fourth step (24-72 h). 

PMID- 24025367
TI  - Publishing 13C metabolic flux analysis studies: a review and future perspectives.
AB  - (13)C-Metabolic flux analysis ((13)C-MFA) is a powerful model-based analysis
      technique for determining intracellular metabolic fluxes in living cells. It has
      become a standard tool in many labs for quantifying cell physiology, e.g., in
      metabolic engineering, systems biology, biotechnology, and biomedical research.
      With the increasing number of (13)C-MFA studies published each year, it is now
      ever more important to provide practical guidelines for performing and publishing
      (13)C-MFA studies so that quality is not sacrificed as the number of publications
      increases. The main purpose of this paper is to provide an overview of good
      practices in (13)C-MFA, which can eventually be used as minimum data standards
      for publishing (13)C-MFA studies. The motivation for this work is two-fold: (1)
      currently, there is no general consensus among researchers and journal editors as
      to what minimum data standards should be required for publishing (13)C-MFA
      studies; as a result, there are great discrepancies in terms of quality and
      consistency; and (2) there is a growing number of studies that cannot be
      reproduced or verified independently due to incomplete information provided in
      these publications. This creates confusion, e.g. when trying to reconcile
      conflicting results, and hinders progress in the field. Here, we review current
      status in the (13)C-MFA field and highlight some of the shortcomings with regards
      to (13)C-MFA publications. We then propose a checklist that encompasses good
      practices in (13)C-MFA. We hope that these guidelines will be a valuable resource
      for the community and allow (13)C-flux studies to be more easily reproduced and
      accessed by others in the future. 

PMID- 24025369
TI  - Waste-to-energy incineration plants as greenhouse gas reducers: a case study of
      seven Japanese metropolises.
AB  - Municipal solid waste (MSW) incineration is a greenhouse gas (GHG) emitter;
      however, if GHG reductions, achieved by accounting for waste-to-energy, exceed
      GHG emissions, incineration can be considered as a net GHG reducer. In Japan,
      only 24.5% of MSW incineration plants perform energy recovery despite 80% of MSW
      being incinerated; therefore, there is great potential to extract more energy
      from MSW. In this study, the factors that should be considered to achieve net GHG
      reductions from incineration were analysed from a life cycle perspective. These
      considerations were then applied to the energy supply requirements in seven
      Japanese metropolises. Firstly, the carbon footprints of approximately 1500
      incineration plants in Japan were calculated. Then, the incineration plants with
      negative carbon footprint values were classified as net GHG reducers. Next, the
      processes that contribute to the carbon footprint were evaluated, and two
      processes-plastic burning and electricity savings-were found to have the greatest
      influence. Based on the results, the energy supply requirements were analysed and
      discussed for seven metropolises (Sapporo, Tokyo, Nagoya, Osaka, Kobe, Takamatsu
      and Fukuoka) taking into account the energy demands of households. In Kobe, 16.2%
      of the electricity demand and 25.0% of the hot water demand could be satisfied by
      incineration to realise a net GHG reducer, although urban design for energy
      utilisation would be required. 

PMID- 24025370
TI  - Reuse of hazardous calcium fluoride sludge from the integrated circuit industry.
AB  - The Chinese integrated circuit industry has been transformed from a small state
      owned sector into a global competitor, but chip manufacturing produces large
      amounts of calcium fluoride sludges (CFS). In China, landfill is a current option
      for treating CFS. In order to solve the problem of unavailable landfill sites and
      prevent fluorine from dissolved CFS polluting water sources, CFS was tested as a
      component for a ceramic product made with sodium borate, sodium phosphate and
      waste alumina using a low-temperature sintering technology, and the effects of
      various factors on characteristics of the ceramic were investigated to optimize
      the process. The best sintering temperature was controlled at 700 degrees C, and
      the optimal raw material ratio of the ceramic was 11% sodium borate, 54% sodium
      phosphate, 30% CFS and 5% waste alumina. The CFS ceramic was characterized by a
      morphological structure and X-ray diffraction. The results indicated that CFS was
      transformed into Na2Ca(PO4)F as an inert and a main crystalline phase in the
      ceramic, which was enclosed by the borophosphate glass. Toxicity characteristic
      leaching procedure, corrosion resistance and compressive strength tests verified
      CFS ceramic as a qualified construction ceramic material, and the fluorine from
      CFS was solidified in the inert crystalline phase, which would not be released to
      cause secondary pollution. This novel technology not only avoids the CFS
      hydrolyzing reaction forming harmful hydrofluoric acid gas at 800 degrees C and
      above, but also produces high-performance ceramics as a construction material, in
      accordance with the concept of sustainable development. 

PMID- 24025371
TI  - Composting for management and resource recovery of invasive Acacia species.
AB  - The feasibility of commercial-scale composting of waste biomass from the control
      of invasive Acacia species was investigated. Pile temperatures exceeded 65oC for
      several months, indicating that the composting process was effective at pathogen
      inactivation and seed destruction. Mineralisation of Acacia biomass was described
      by a two-component, first-order exponential model; the pool sizes for labile and
      recalcitrant organic matter (OM) were similar and in the approximate ranges: 360
      410 g kg(-1) and 350-390 g kg(-1) of initial OM, respectively. Concentrations of
      conservative nutrients increased proportionally to OM mineralisation, enriching
      the compost as an agricultural nutrient source. Nitrogen concentrations also
      increased, but were more dynamic as nitrogen losses were difficult to control,
      although we suggest that they may be potentially minimised by restricting the
      turning frequency. The physicochemical characteristics of the stabilised end
      product, and the high OM content and low electrical conductivity (<1.2 dS m(-1)),
      in particular, were suitable for soil improvement or as substrate components. 

PMID- 24025372
TI  - Physical knowledge of household waste in Algeria: generation and composition in
      the town of Annaba.
AB  - We investigated the physical composition of household waste in the town of
      Annaba, Algeria. The study was based on an adequate sampling protocol that takes
      into account the constraints of Algerian cities. Annaba was taken as a case study
      to check the situation in Algeria. Ninety to 120 kg was sorted for each type of
      habitat in the city during four seasons, from 2010 to 2011, according to 11
      components of household waste. Variations in the production ratio and percentages
      of all components were recorded according to the seasons and the type of habitat
      during the four campaigns of characterization. Analysis of variance showed a
      significant difference of the waste composition by habitat type. A pairwise
      multiple comparisons using the Tukey test of the sampled habitat types was also
      carried out, which indicated no significant differences between the habitat type
      concerning paper, plastic, composite and glass variables. But for the remaining
      components, the study revealed, with a significance limit of 0.05, a clear
      difference in the average composition of the waste according to the type of
      habitat. 

PMID- 24025373
TI  - Organic wastes to enhance phyto-treatment of diesel-contaminated soil.
AB  - Toxic inorganic and organic chemicals are major contributors to environmental
      contamination and pose major health risks to human population. In this work,
      Dracaena reflexa and Podocarpus polystachyus were investigated for their
      potential to remove hydrocarbons from 2.5% and 1% diesel fuel-contaminated soil
      amended individually with 5% organic wastes (tea leaf, soy cake and potato skin)
      for a period of 270 days. Loss of 90% and 99% oil was recorded in soil
      contaminated with 2.5% and 1% oil with soy cake amendment, respectively, compared
      with 52% and 62% in unamended soil with D. reflexa at the end of 270 days.
      Similarly, 84% and 91% oil loss was recorded for P. polystachyus amended with
      organic wastes in 2.5% and 1% oil, respectively. Diesel fuel disappeared more
      rapidly in the soil amendment with SC than in other organic waste
      supplementation. It was evident that plants did not accumulate hydrocarbon from
      the soil, while the number of hydrocarbon-utilizing bacteria was high in the
      rhizosphere, thus suggesting that the mechanism of the oil degradation was
      rhizodegradation. The kinetic model result indicated a high rate of degradation
      in soil amendment with SC at 1% with D. reflexa compared with other treatments.
      Thus, a positive relationship was observed between diesel hydrocarbon degradation
      with plant biomass production. Dracaena reflexa with organic wastes amendment has
      a greater potential of restoring hydrocarbon-contaminated soil compared to P.
      polystachyus plant. 

PMID- 24025374
TI  - Integrating tuberculosis services into a PMTCT HIV programme in South Africa.

PMID- 24025375
TI  - Programmatic approaches to screening for active tuberculosis.
AB  - Passive case finding, the detection of tuberculosis (TB) cases among persons
      presenting to health facilities with symptoms suggestive of TB, has remained the
      principal public health approach for TB diagnosis. While this approach, in
      combination with improved treatment, has led to substantial global progress, the
      overall epidemiological impact has been inadequate. Stagnating case notifications
      and sluggish decline in incidence prompt the pursuit of a more active approach to
      TB case detection. Screening among contacts of TB patients and people living with
      human immunodeficiency virus infection, long recommended, needs scaling up.
      Screening in other risk groups may also be considered, depending on the
      epidemiological situation. The World Health Organization (WHO) has recently
      produced recommendations on systematic screening for active TB, which set out
      principles and provide guidance on the prioritisation of risk groups for
      screening and choice of screening and diagnostic algorithms. With a view to help
      translate WHO recommendations into practice, this concluding article of the State
      of the Art series discusses programmatic approaches. Published literature is
      scanty. However, considerable field experience exists to draw important lessons.
      Cautioning against a hasty pursuit of active case finding, the article stresses
      that programmatic implementation of TB screening requires a systematic approach.
      Important considerations should include setting clear goals and objectives based
      on a thorough assessment of the situation; considering the place of TB screening
      in the overall approach to enhancing TB detection; identifying and prioritising
      risk groups; choosing appropriate screening and diagnostic algorithms; and
      pursuing setting-specific implementation strategies with engagement of relevant
      partners, due attention to ethical considerations and built-in monitoring and
      evaluation. 

PMID- 24025376
TI  - Tuberculin survey in Bangladesh, 2007-2009: prevalence of tuberculous infection
      and implications for TB control.
AB  - OBJECTIVES: To assess the prevalence of tuberculous infection and the annual risk
      of tuberculous infection (ARTI) for 2007-2009 in Bangladesh, approximately 45
      years after the first tuberculin survey in 1964-1966. METHODS: A tuberculin
      survey was conducted along with the National Tuberculosis Disease Prevalence
      Survey in 2007-2009. This was a multistaged community-based, cross-sectional
      survey, including 17,718 children aged 5-14 years. The prevalence of tuberculous
      infection was estimated using the mixture method and a cut-off point of >= 8 mm.
      RESULTS: The prevalence of infection was 10.0% (interquartile range [IQR] 8.6
      12.2) in children aged 5-9 years and 17.9% (IQR 15.4-20.2) in those aged 10-14
      years using the mixture analysis. Prevalence was 12.4% (95% confidence interval
      [CI] 11.7-13.1) in children aged 5-9 years and 22.6% (95%CI 21.6-23.4) in those
      aged 10-14 years using a cut-off point of >= 8 mm. The estimated ARTI was
      respectively 1.5% and 1.7% in 5-9 and 10-14 year olds using the mixture method
      and respectively 1.9% and 2.1% using the cut-off method. CONCLUSIONS: The
      moderate reduction in the prevalence of infection and slow decline of the ARTI
      after two decades of DOTS implementation indicates considerable ongoing
      transmission.

PMID- 24025377
TI  - Comparison of different methods and times for reading the tuberculin skin test.
AB  - BACKGROUND: Current guidelines vary on the recommended method and time for
      measuring tuberculin skin test (TST) indurations. OBJECTIVE: To evaluate the best
      time and method for assessing TST results and which purified protein derivative
      (PPD) to administer. DESIGN: Standard PPD (PPD-S) and PPD-RT23 were applied
      concurrently on each forearm in random order in 78 nurses. MEASUREMENTS: TST
      induration was measured at 48, 72 and 96 h by two nurses by palpation and a
      ruler, palpation and a Vernier caliper, ballpoint pen and a ruler or ballpoint
      pen and a Vernier caliper. TST differences were assessed using mixed-effects
      analysis. We also assessed the rate of false-positive/-negative results and the
      variability of the TST measurements. RESULTS: We performed 767 TST measurements.
      The adjusted mean TST size was larger with PPD-S than with PPD-RT23 (12.8 vs.
      10.8 mm, P < 0.001), and at 72 h than at 48 h and 96 h (13.4 vs. 11.8 vs. 10.1
      mm, P < 0.05). The smallest number of false results was observed with PPD-S, the
      ballpoint pen-ruler and at 72 h; palpation+ruler had the least variability at 72
      h. CONCLUSIONS: The TST should ideally be performed with PPD-S and measured at 72
      h with the ballpoint pen+ruler or palpation+ruler methods.

PMID- 24025378
TI  - Drug-resistant tuberculosis in children in Thailand.
AB  - SETTING: Few data on drug-resistant (DR) tuberculosis (TB) in children are
      available in Thailand. OBJECTIVES: To evaluate the rate, clinical features and
      risk of DR-TB in children. DESIGN: Observational prospective study conducted in
      children diagnosed with TB at a tertiary care centre in Bangkok. RESULTS: Of 230
      children diagnosed with TB, the median age was 6.5 years; 63% had identified
      adult source cases, and only 7% had received prior isoniazid treatment for latent
      tuberculous infection. Of the 195 (85%) specimens submitted, 57 (25%) were
      positive using culture or polymerase chain reaction. Of the 53 positive specimens
      available for drug susceptibility testing (DST), 18 (34%) had any resistance, 13
      (24.5%) were mono-resistant, 2 (3.8%) polyresistant and 3 (5.7%) were multidrug
      resistant. In multivariate analysis, prior TB treatment (P < 0.001), presence of
      atelectasis (P = 0.039) or lobar consolidation (P = 0.012) on chest X-ray were
      associated with DR-TB. DR-TB required longer treatment but there were no
      differences in rate of cure, treatment completion or death. CONCLUSIONS: The high
      rate of DR-TB underscores the importance of routine DST. History of treatment and
      drug susceptibility in source cases was useful in guiding initial treatment in
      children.

PMID- 24025379
TI  - Integration of tuberculosis and prevention of mother-to-child transmission of HIV
      programmes in South Africa.
AB  - SETTING: One of the rural districts in KwaZulu-Natal Province, the epicentre of
      the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics in South
      Africa. OBJECTIVES: To assess the integration of TB services into the prevention
      of mother-to-child transmission of HIV (PMTCT) programme and identify barriers to
      the integration of services. DESIGN: Cross-sectional survey using exit interviews
      with pregnant women attending 10 antenatal care (ANC) clinics. Review of ANC
      PMTCT facility routine data. Qualitative interviews with 26 key informants on
      barriers to integration of TB-PMTCT services. RESULTS: Of 150 women interviewed,
      112 (75%) reported being educated on TB symptoms on the day of their visit; 56%
      were screened for TB symptoms and 27% were suspected to have TB; 26 (17%) women
      were HIV-positive and 2 (8%) were co-infected with TB. There was no record of
      provision of isoniazid prophylaxis for PMTCT clients with latent tuberculous
      infection. The predominant barriers to the integration of TB-PMTCT services
      included lack of skilled providers and their supervision, the physical layout of
      the TB-PMTCT services and the service delivery mechanisms. CONCLUSION: The
      integration of TB prevention and care into the PMTCT programme was inadequate.
      Integration of TB services into the ANC PMTCT programme will require strong
      leadership to address barriers such as training gaps, lack of supervision and
      service delivery mechanisms.

PMID- 24025380
TI  - Impact of expanded antiretroviral use on incidence and prevalence of tuberculosis
      in children with HIV in Kenya.
AB  - SETTING: Antiretroviral therapy (ART) reduces pulmonary tuberculosis (PTB) in
      human immunodeficiency virus (HIV) infected children. Recent ART recommendations
      have increased the number of children on ART. OBJECTIVE: To determine the
      prevalence and incidence of TB in HIV-infected children after the implementation
      of expanded ART guidelines. DESIGN: A prospective cohort study including HIV
      infected children aged 6 weeks to 14 years was conducted in Kenya. The primary
      outcome measure was clinically diagnosed TB. Study participants were screened for
      prevalent TB at enrollment using Kenya's national guidelines and followed at
      monthly intervals to detect incident TB. Predictors of TB were assessed using
      logistic regression and Cox proportional hazards regression. RESULTS: Of 689
      participants (median age 6.4 years), 509 (73.9%) were on ART at baseline. There
      were 51 cases of prevalent TB (7.4%) and 10 incident cases, with over 720.3 child
      years of observation (incidence 1.4 per 100 child-years). Months on ART (adjusted
      hazard ratio [aHR] 0.91, P = 0.003; aOR 0.91, P< 0.001) and months in care before
      ART (aHR 0.87, P= 0.001; aOR 0.92, P < 0.001) were protective against incident
      and prevalent TB. CONCLUSIONS: ART was protective against TB in this cohort of
      HIV-infected children with high levels of ART use. Optimal TB prevention
      strategies should emphasize early ART in children.

PMID- 24025381
TI  - Outcomes in HIV-infected adults with tuberculosis at clinics with and without co
      located HIV clinics in Botswana.
AB  - SETTING: Gaborone, Botswana. OBJECTIVE: To determine if starting anti
      tuberculosis treatment at clinics in Gaborone without co-located human
      immunodeficiency virus (HIV) clinics would delay time to highly active
      antiretroviral therapy (HAART) initiation and be associated with lower survival
      compared to starting anti-tuberculosis treatment at clinics with on-site HIV
      clinics. DESIGN: Retrospective cohort study. Subjects were HAART-naive, aged >=
      21 years with pulmonary tuberculosis (TB), HIV and CD4 counts <= 250 cells/mm(3)
      initiating anti-tuberculosis treatment between 2005 and 2010. Survival at
      completion of anti-tuberculosis treatment or at 6 months post-treatment
      initiation and time to HAART after anti-tuberculosis treatment initiation were
      compared by clinic type. RESULTS: Respectively 259 and 80 patients from clinics
      without and with on-site HIV facilities qualified for the study. Age, sex, CD4,
      baseline sputum smears and loss to follow-up rate were similar by clinic type.
      Mortality did not differ between clinics without or with on-site HIV clinics
      (20/250, 8.0% vs. 8/79, 10.1%, relative risk 0.79, 95%CI 0.36-1.72), nor did
      median time to HAART initiation (respectively 63 and 66 days, P = 0.53).
      CONCLUSION: In urban areas where TB and HIV programs are separate, geographic co
      location alone without further integration may not reduce mortality or time to
      HAART initiation among co-infected patients.

PMID- 24025382
TI  - Risk factors for treatment default among adult tuberculosis patients in
      Indonesia.
AB  - SETTING: Defaulting from anti-tuberculosis treatment hinders tuberculosis (TB)
      control. OBJECTIVE: To identify potential defaulters. DESIGN: We conducted a
      cohort study in newly diagnosed Indonesian TB patients. We administered a
      questionnaire, prospectively identified defaulters (discontinued treatment >= 2
      weeks) and assessed risk factors using Cox's regression. RESULTS: Of 249
      patients, 39 (16%) defaulted, 61% in the first 2 months. Default was associated
      with liver disease (HR 3.40, 95%CI 1.02-11.78), chest pain (HR 2.25, 95%CI 1.06
      4.77), night sweats (HR 1.98, 95%CI 1.03-3.79), characteristics of the head of
      the household (self-employed, HR 2.47, 95%CI 1.15-5.34; patient's mother, HR
      7.72, 95%CI 1.66-35.88), household wealth (HR 4.24, 95%CI 1.12-16.09), walking to
      clinic (HR 4.53, 95%CI 1.39-14.71), being unaccompanied at diagnosis (HR 30.49,
      95%CI 7.55-123.07) or when collecting medication (HR 3.34, 95%CI 1.24-8.98) and
      low level of satisfaction with the clinic (HR 3.85, 95%CI 1.17-12.62) or doctors
      (HR 2.45, 95%CI 1.18-5.10). Health insurance (HR 0.24, 95%CI 0.07-0.74) and
      paying for diagnosis (HR 0.14, 95%CI 0.04-0.48) were protective. CONCLUSION:
      Defaulting is common and occurs early. Interventions that improve clinic
      services, strengthen patient support and increase insurance coverage may reduce
      default in Indonesia.

PMID- 24025383
TI  - Prognostic factors associated with mortality before and during anti-tuberculosis
      treatment.
AB  - OBJECTIVE: To identify factors associated with death before the start of anti
      tuberculosis treatment, and early and late during treatment, among adult
      Taiwanese with culture-positive pulmonary tuberculosis (PTB). METHOD: All adult
      culture-positive PTB patients in Taipei, Taiwan, were included in a retrospective
      cohort study in 2005-2010. RESULTS: Of 4438 patients (mean age 64.6 years, 70.6%
      male), 76.8% were successfully treated, 5.4% died before start of treatment, 9.0%
      died within 8 weeks of treatment initiation and 8.8% died >8 weeks after
      treatment initiation. After controlling for potential confounders, age >= 65
      years and male sex were associated with higher risks of death at all time periods
      investigated. High school education or higher reduced the risk of death before
      the start of and during treatment, while unemployment increased the risk of
      mortality during treatment. Cavity on chest X-ray and positivity for acid-fast
      bacilli were associated with lower risk of mortality before the start of
      treatment. CONCLUSION: To lower mortality among adult culture-positive PTB
      patients, it is imperative for clinicians to maintain high awareness of TB and
      provide more intensive care early, especially for men, the elderly and people
      with lower socio-economic status (e.g., the unemployed and less educated).

PMID- 24025384
TI  - Validation of sputum smear results in the Electronic TB Register for the
      management of tuberculosis, South Africa.
AB  - BACKGROUND: The accuracy of tuberculosis (TB) surveillance systems is paramount
      in TB control. In South Africa, information from the laboratory is not directly
      linked to the Electronic TB Register (ETR). OBJECTIVE: To validate smear results
      recorded in the ETR with those recorded in the laboratory. METHODS: A
      retrospective evaluation was conducted among all sputum smear-positive TB
      patients recorded in the ETR during the fourth quarter of 2009 in KwaZulu-Natal
      Province. RESULTS: Of 1036 smear-positive patients recorded in the ETR, 683
      (65.9%) had positive results recorded in the laboratory register. Only 364
      (53.2%) had their smear results recorded in the ETR at the end of the intensive
      phase of treatment; of 326 (89.6%) recorded as converted to smear-negative, 224
      (61.5%) were confirmed as smear-negative in the laboratory. Of 331 patients with
      end-of-treatment results in the ETR, 302 (91.2%) were recorded as cured, but only
      105 (34.8%) were confirmed in the laboratory. CONCLUSIONS: Over a third of TB
      patients registered as smear-positive in the ETR could not be confirmed based on
      laboratory results. Many patients did not have a laboratory record, lending to
      uncertainty as to the validity of the smear results and treatment outcomes
      recorded in the ETR.

PMID- 24025385
TI  - Epidemiological evaluation of spatiotemporal and genotypic clustering of
      Mycobacterium tuberculosis in Ontario, Canada.
AB  - BACKGROUND: In Canada, tuberculosis (TB) rates are at a historic low, with the
      remaining risk concentrated in a few vulnerable population subgroups. OBJECTIVES:
      To describe the epidemiology of TB in the Canadian province of Ontario and to
      characterise risk factors associated with transmission events, identified using
      genetic typing techniques. DESIGN: Retrospective analysis of 2186 culture
      positive TB cases between August 2007 and December 2011. Temporal trends and risk
      of spatiotemporal and genotypic clustering were evaluated using Poisson and
      logistic regression models. RESULTS: Being in a spatiotemporal cluster was
      associated with Aboriginal status (odds ratio [OR] 3.63, 95% confidence interval
      [CI] 1.23-10.71). Cases in genotypic clusters were more likely to report
      homelessness as a risk factor (adjusted OR [aOR] 2.92, 95%CI 1.74-4.90) or be
      male (aOR 1.35, 95%CI 1.09-1.68), and were less likely to be aged >= 65 years
      (aOR 0.63, 95%CI 0.49-0.82), foreign-born (aOR 0.32, 95%CI 0.24-0.43) or
      Aboriginal (aOR 0.40, 95%CI 0.16-0.99). The Beijing lineage had an annual rate of
      increase of almost 10% (P = 0.047), and was associated with genotypic clustering
      (aOR 2.84, 95%CI 2.19-3.67). CONCLUSION: Genotypic data suggest that disease
      clusters are smaller, but far more common, than would be estimated using
      spatiotemporal clustering.

PMID- 24025386
TI  - Cost-effectiveness of Xpert(r) MTB/RIF for diagnosing pulmonary tuberculosis in
      the United States.
AB  - SETTING: Conventional approaches to tuberculosis (TB) diagnosis and resistance
      testing are slow. The Xpert(r) MTB/RIF assay is an emerging molecular diagnostic
      assay for rapid TB diagnosis, offering results within 2 hours. However, the cost
      effectiveness of implementing Xpert in settings with low TB prevalence, such as
      the United States, is unknown. OBJECTIVE: We evaluated the cost-effectiveness of
      incorporating Xpert into TB diagnostic algorithms in the United States compared
      to existing diagnostics. DESIGN: A decision-analysis model compared current TB
      diagnostic algorithms in the United States to algorithms incorporating Xpert.
      Primary outcomes were the costs and quality-adjusted life years (QALYs) accrued
      with each strategy; cost-effectiveness was represented using incremental cost
      effectiveness ratios (ICER). RESULTS: Xpert testing of a single sputum sample
      from TB suspects is expected to result in lower total health care costs per
      patient (US2673) compared to diagnostic algorithms using only sputum microscopy
      and culture (US2728) and improved health outcomes (6.32 QALYs gained per 1000 TB
      suspects). Compared to existing molecular assays, implementation of Xpert in the
      United States would be considered highly cost-effective (ICER US39992 per QALY
      gained). CONCLUSION: TB diagnostic algorithms incorporating Xpert in the United
      States are highly cost-effective.

PMID- 24025387
TI  - Cost-effectiveness of routine diagnostic evaluation of pulmonary tuberculosis in
      a primary care unit in Brazil.
AB  - SETTING: Primary health care unit in Rio de Janeiro City, Brazil. OBJECTIVE: To
      estimate and compare the cost-effectiveness of strategies used for passive case
      finding of pulmonary tuberculosis (PTB) cases using tests available at the
      primary care level. DESIGN: Data on PTB suspects were reviewed, and a decision
      model was developed using sputum smear microscopy and chest radiography (CXR)
      according to three different strategies for PTB detection. A cost-effectiveness
      analysis was performed to estimate the cost per correct PTB diagnosis.
      Mycobacterial culture was used to calculate the effectiveness of the strategies.
      Unit costs of health resource utilisation were obtained from the payer's
      perspective (the Brazilian Public Health System). RESULTS: For the evaluation of
      254 PTB suspects, the total costs of strategies ranged from US$5369 to US$5944;
      the probability of a correct PTB diagnosis ranged from 0.66 to 0.86; the number
      of visits required to complete the diagnostic process ranged from two to three,
      and cost per PTB case identified ranged from US$47.93 to US$53.07. The cost
      effectiveness of the three strategies studied varied between US$56.69 and
      US$72.55 per correct PTB case detected. CONCLUSION: A strategy in which sputum
      smears and CXR were requested for all PTB suspects at the initial evaluation was
      cost-effective, had a high probability of correct PTB diagnosis and could be
      accomplished in two visits.

PMID- 24025388
TI  - Mycobacterium tuberculosis detection in blood using multiplex nested polymerase
      chain reaction.
AB  - SETTING: Polymerase chain reaction (PCR) offers great promise for the rapid,
      sensitive and specific diagnosis of tuberculosis (TB). However, blood TB PCR is
      still not standardised. OBJECTIVE: Evaluation of the Blacklight(r) Card to
      standardise TB PCR in blood samples using a multiplex nested PCR method targeting
      insertion sequence 6110 and MPB64 sequence for use as an auxiliary tool in the
      diagnosis of TB. DESIGN: The study focused on the standardisation of the
      Blacklight Card as a new extraction tool and its evaluation using 130 blood
      samples randomly collected from patients with clinical symptoms of TB. RESULTS:
      Of 130 cases, PCR was positive in 22 samples (17%). The overall sensitivity and
      specificity of the PCR assay was respectively 95.7% and 100%; the positive and
      negative predictive values were respectively 85.1% and 99.2%. CONCLUSION: These
      results suggest that for the detection of Mycobacterium tuberculosis DNA in
      peripheral blood mononuclear cells, the Blacklight Card may be a useful tool for
      the rapid diagnosis of disseminated and extra-pulmonary forms of TB as well as in
      difficult-to-diagnose cases in which a diagnosis is urgently needed due to the
      severity of the patient's status.

PMID- 24025389
TI  - Evaluating the clinical significance of serum HE4 levels in lung cancer and
      pulmonary tuberculosis.
AB  - OBJECTIVE: To evaluate whether serum human epididymis protein 4 (HE4) levels
      could be used as a marker to differentiate lung cancer from pulmonary
      tuberculosis (PTB) and as a prognostic indicator in patients with non-small-cell
      lung cancer (NSCLC). DESIGN: HE4 levels were measured in serum samples from 106
      healthy controls, 190 lung cancer patients, 114 patients with PTB and 24 patients
      with pneumonia using enzyme-linked immunosorbent assay. RESULTS: Serum HE4 levels
      in lung cancer patients were significantly higher than those in patients with PTB
      and healthy controls (P < 0.001). Using the optimal cut-off value of 94.01
      pmol/l, HE4 levels distinguished lung cancer from PTB with a sensitivity of 61.6%
      and a specificity of 93.0%. After adjusting for age and smoking status, a binary
      unconditional logistic regression model provided a sensitivity of 67.4% and a
      specificity of 86.0% for differentiating between these two diseases. In the NSCLC
      group, serum HE4 levels were significantly higher in patients at advanced stages
      (Stage I-II vs. Stage III-IV, P = 0.02). Higher levels of serum HE4 (>= 83.90
      pmol/l) were significantly correlated with a worse 3-year survival rate for
      patients with NSCLC (P < 0.05). CONCLUSION: Serum HE4 may be used as a potential
      marker to differentiate lung cancer from PTB and healthy controls. In addition,
      higher levels of HE4 predict poor prognosis in NSCLC patients.

PMID- 24025390
TI  - Barriers to tuberculosis care for drug users in two provinces of China: a
      qualitative study.
AB  - SETTING: Two compulsory drug rehabilitation centres in Yunnan and Sichuan
      Provinces, Southwest China. OBJECTIVE: To understand barriers to tuberculosis
      (TB) care among drug users in China, and to provide policy recommendations to
      improve TB control in the drug-using population. DESIGN: A qualitative study was
      designed using in-depth interviews with 147 drug users with TB and 12 key
      informants. Drug users were purposively selected from two compulsory drug
      rehabilitation centres and key informants from national and provincial justice
      administration, local TB control dispensaries and compulsory drug rehabilitation
      centres. RESULTS: Lack of health awareness and knowledge was reported as one
      barrier to TB care among drug users. The majority of the respondents lacked
      social support and perceived fear and stigma when seeking TB care. More than half
      of the respondents who had discontinued their anti-tuberculosis treatment
      reported that this was due to drug use. Limited provision of TB care in the
      compulsory drug rehabilitation centres and local TB control dispensaries was also
      reported as one of the barriers to TB care among drug users. CONCLUSIONS: These
      findings suggest that barriers to TB care for drug users are associated not only
      with the drug users themselves, but also with the providers and societal factors.
      Health professionals and policy makers should be aware of these barriers in
      China.

PMID- 24025391
TI  - A qualitative analysis among regular waterpipe tobacco smokers in London
      universities.
AB  - BACKGROUND: Waterpipe smoking is popular in the West despite the significant harm
      associated with its use. Little is known about the habits and practices of
      British smokers. DESIGN: A total of 32 regular waterpipe smokers attended focus
      groups, where trained facilitators explored knowledge, belief and attitudes to
      waterpipes. Transcripts were thematically analysed and grouped into seven broad
      categories. RESULTS: Waterpipes played a clearly defined social role, accentuated
      by reduced harm perception and greater social acceptance than cigarettes.
      Knowledge about waterpipes was lacking, partly due to the lack of media
      attention. Addiction was described as a 'social addiction', although this may
      mask true nicotine addiction. Waterpipe smokers were less interested in quitting
      due to intermittent smoking patterns, reinforcing the belief of reduced exposure
      to harm. Legislative issues were explored, including the need to legislate on
      waterpipes on a par with cigarettes. CONCLUSION: Waterpipe smokers exhibited
      specific habits and attitudes not traditionally seen in cigarette smokers. It is
      important to encourage education to dispel the myths surrounding reduced harm
      perception and addiction to tackle its strong social acceptance. Legislation
      should play a more active role in prevention and education, and more emphasis
      should be placed on gathering nationwide epidemiological data to gauge the
      potential for escalation.

PMID- 24025392
TI  - A rare case of Marfan syndrome and concomitant alpha-1 antitrypsin deficiency.

PMID- 24025393
TI  - Efficacy of KTP laser in the treatment of severe obstructive tracheobronchial
      tuberculosis: report of two cases.

PMID- 24025394
TI  - Sex-specific expression of CTNNB1 in the gonadal morphogenesis of the chicken.
AB  - BACKGROUND: Beta-catenin (CTNNB1), as a key transcriptional regulator in the WNT
      signal transduction cascade, plays a pivotal role in multiple biological
      functions such as embryonic development and homeostasis in adults. Although it
      has been suggested that CTNNB1 is required for gonad development and maintenance
      of ovarian function in mice, little is known about the expression and functional
      role of CTNNB1 in gonadal development and differentiation in the chicken
      reproductive system. METHODS: To examine sex-specific, cell-specific and temporal
      expression of CTNNB1 mRNA and protein during gonadal development to maturation of
      reproductive organs, we collected left and right gonads apart from mesonephric
      kidney of chicken embryos on embryonic day (E) 6, E9, E14, E18, as well as
      testes, oviduct and ovaries from 12-week-old and adult chickens and performed
      quantitative PCR, in situ hybridization, and immunohistochemical analyses. In
      addition, localization of Sertoli cell markers such as anti-Mullerian hormone
      (AMH), estrogen receptor alpha (ESR1), cyclin D1 (CCND1) and N-cadherin (CDH2)
      during testicular development was evaluated. RESULTS: Results of the present
      study showed that CTNNB1 mRNA and protein are expressed predominantly in the
      seminiferous cords on E6 to E14 in the male embryonic gonad, and are mainly
      localized to the medullary region of female embryonic gonads from E6 to E9. In
      addition, CTNNB1 mRNA and protein are abundant in the Sertoli cells in the testes
      and expressed predominantly in luminal epithelial cells of the oviduct, but not
      in the ovaries from 12-week-old and adult chickens. Concomitant with CTNNB1, AMH,
      ESR1, CCND1 and CDH2 were detected predominantly in the seminiferous cord of the
      medullary region of male gonads at E9 (after sex determination) and then
      maintained or decreased until hatching. Interestingly, AMH, ESR1, CCND1 and CDH2
      were located in seminiferous tubules of the testes from 12-weeks-old chickens and
      ESR1, CCND1 and CDH2 were expressed predominantly in the Sertoli cells within
      seminiferous tubules of adult testes. CONCLUSIONS: Collectively, these results
      revealed that CTNNB1 is present in gonads of both sexes during embryonic
      development and it may play essential roles in differentiation of Sertoli cells
      during formation of seminiferous tubules during development of the testes.

PMID- 24025395
TI  - Topological relics of symmetry breaking: winding numbers and scaling tilts from
      random vortex-antivortex pairs.
AB  - I show that random distributions of vortex-antivortex pairs (rather than of
      individual vortices) lead to scaling of typical winding numbers W trapped inside
      a loop of circumference C with the square root of that circumference, W ~?C, when
      the expected winding numbers are large, |W| ? 1. Such scaling is consistent with
      the Kibble-Zurek mechanism (KZM), with <W2> inversely proportional to xi, the
      typical size of the domain that can break symmetry in unison. (The dependence of
      xi on quench rate is predicted by KZM from critical exponents of the phase
      transition.) Thus, according to KZM, the dispersion ?<W2> scales as ?C/xi for
      large W. By contrast, a distribution of individual vortices with randomly
      assigned topological charges would result in the dispersion scaling with the
      square root of the area inside C (i.e., ~?<W2> ~C). Scaling of the dispersion of
      W as well as of the probability of detection of non-zero W with C and xi can be
      also studied for loops so small that non-zero windings are rare. In this case I
      show that dispersion varies not as 1/?xi, but as 1/xi, which results in a
      doubling of the scaling of dispersion with the quench rate when compared to the
      large |W| regime. Moreover, the probability of trapping of non-zero W becomes
      approximately equal to <W2>, and scales as 1/xi2. This quadruples--as compared
      with ?<W2>? ?C/ xi valid for large W--the exponent in the power law dependence of
      the frequency of trapping of |W| = 1 on xi when the probability of |W| > 1 is
      negligible. This change of the power law exponent by a factor of four--from 1?xi
      for the dispersion of large W to 1/xi2 for the frequency of non-zero W when |W| >
      1 is negligibly rare--is of paramount importance for experimental tests of KZM.

PMID- 24025397
TI  - Achieving smoke-free mental health services: lessons from the past decade of
      implementation research.
AB  - The culture of smoking by patients and staff within mental health systems of care
      has a long and entrenched history. Cigarettes have been used as currency between
      patients and as a patient management tool by staff. These settings have
      traditionally been exempt from smoke-free policy because of complex held views
      about the capacity of people with mental disorder to tolerate such policy whilst
      they are acutely unwell, with stakeholders' continuing fierce debate about
      rights, choice and duty of care. This culture has played a significant role in
      perpetuating physical, social and economic smoking associated impacts experienced
      by people with mental disorder who receive care within mental health care
      settings. The past decade has seen a clear policy shift towards smoke-free mental
      health settings in several countries. While many services have been successful in
      implementing this change, many issues remain to be resolved for genuine smoke
      free policy in mental health settings to be realized. This literature review
      draws on evidence from the international published research, including national
      audits of smoke-free policy implementation in mental health units in Australia
      and England, in order to synthesise what we know works, why it works, and the
      remaining barriers to smoke-free policy and how appropriate interventions are
      provided to people with mental disorder. 

PMID- 24025399
TI  - Robust infrared-shielding coating films prepared using perhydropolysilazane and
      hydrophobized indium tin oxide nanoparticles with tuned surface plasmon
      resonance.
AB  - Robust infrared (IR)-shielding coating films were prepared by dispersing indium
      tin oxide (ITO) nanoparticles (NPs) in a silica matrix. Hydrophobized ITO NPs
      were synthesized via a liquid phase process. The surface plasmon resonance (SPR)
      absorption of the ITO NPs could be tuned by varying the concentration of Sn
      doping from 3 to 30 mol %. The shortest SPR wavelength and strongest SPR
      absorption were obtained for the ITO NPs doped with 10% Sn because they possessed
      the highest electron carrier density. Coating films composed of a continuous
      silica matrix homogeneously dispersed with ITO NPs were obtained using
      perhydropolysilazane (PHPS) as a precursor. PHPS was completely converted to
      silica by exposure to the vapor from aqueous ammonia at 50  degrees C. The
      prepared coating films can efficiently shield IR radiation even though they are
      more than 80% transparent in the visible range. The coating film with the
      greatest IR-shielding ability completely blocked IR light at wavelengths longer
      than 1400 nm. The pencil hardness of this coating film was 9H at a load of 750 g,
      which is sufficiently robust for applications such as automotive glass. 

PMID- 24025396
TI  - A review of vaccine approaches for West Nile virus.
AB  - The West Nile virus (WNC) first appeared in North America in 1999. The North
      American lineages of WNV were characterized by the presence of neuroinvasive and
      neurovirulent strains causing disease and death in humans, birds and horses. The
      2012 WNV season in the United States saw a massive spike in the number of
      neuroinvasive cases and deaths similar to what was seen in the 2002-2003 season,
      according to the West Nile virus disease cases and deaths reported to the CDC by
      year and clinical presentation, 1999-2012, by ArboNET (Arboviral Diseases Branch,
      Centers for Disease Control and Prevention). In addition, the establishment and
      recent spread of lineage II WNV virus strains into Western Europe and the
      presence of neurovirulent and neuroinvasive strains among them is a cause of
      major concern. This review discusses the advances in the development of vaccines
      and biologicals to combat human and veterinary West Nile disease. 

PMID- 24025398
TI  - Expanding role of delta-like 4 mediated notch signaling in cardiovascular and
      metabolic diseases.
AB  - Cardiometabolic disease, a global health threat, has been linked to chronic
      inflammation, in which activated macrophages play a key role. Macrophages are
      highly heterogeneous hematopoietic cells found in nearly every tissue in the
      body. Various stimuli recruit monocytes into the cardiovascular system and
      metabolic organs, where they differentiate to macrophages, and activate these pro
      inflammatory phagocytes, leading to the initiation and development of
      inflammation in these organs. Key regulators of macrophage activation therefore
      may serve as therapeutic targets for cardiometabolic disease. The Notch signaling
      pathway, involving 5 ligands and 4 receptors, regulates the differentiation of
      various cell types during development, and also contributes to the disease
      processes in adults. We found that the Notch ligand delta-like 4 (Dll4) activates
      macrophages in vitro as determined by the induction of genes and pathways
      associated with cardiovascular and metabolic disorders. Our recent study
      demonstrated in vivo that blockade of Dll4 by a neutralizing antibody attenuates
      key features typical of cardiovascular and metabolic diseases, such as
      accumulation of activated macrophages in arteries and fat; chronic
      atherosclerosis; arterial and valvular calcification; insulin resistance; and
      fatty liver. These results suggest that Dll4-mediated Notch signaling
      participates in the shared disease mechanisms for cardiovascular and metabolic
      disorders. This review summarizes the role of macrophages and Dll4/Notch
      signaling in the development of inflammation in both the cardiovascular system
      and metabolic organs. 

PMID- 24025400
TI  - Elevated periimplantation uterine natural killer cell density in human
      endometrium is associated with impaired corticosteroid signaling in decidualizing
      stromal cells.
AB  - BACKGROUND: Decidualizing human endometrial stromal cells (HESCs) profoundly up
      regulate 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1), the enzyme that
      converts inert cortisone to active cortisol. We postulated that the induction of
      a cortisol gradient upon decidualization of the periimplantation endometrium may
      impact on the uterine natural killer (uNK) cell population and on local
      expression of corticosteroid-dependent target genes. METHODS: Midluteal
      endometrial biopsies (n = 55) were processed for uNK cell (CD56) analysis and
      primary HESC cultures. The cultures remained either untreated or were
      decidualized for 4 or 8 days. A tissue microarray was constructed from endometria
      with normal (n = 18) and elevated uNK cell (n = 18) scores. An abnormal uNK cell
      test was defined as greater than 5% CD56(+) cells in the subluminal stroma.
      RESULTS: Increased uNK cell density was associated with lower endometrial
      expression of 11betaHSD1 and mineralocorticoid receptor (MR) but not
      glucocorticoid receptor in vivo. Elevated uNK cell density also corresponded to
      impaired induction of key decidual markers (11betaHSD1, prolactin, and insulin
      like growth factor binding protein-1) and MR-dependent enzymes
      (dehydrogenase/reductase member 3 and retinol saturase) in differentiating HESC
      cultures. Increased uNK cell density in vivo was not associated with increased in
      vitro expression of either IL-15 or IL-11, two cytokines implicated in uNK cell
      regulation. CONCLUSIONS: Elevated levels of uNK cells in the stroma underlying
      the surface epithelium are associated with inadequate cortisol biosynthesis by
      resident decidualizing cells and suboptimal induction of key MR-dependent enzymes
      involved in lipid biogenesis and the retinoid transport pathway. Our observations
      suggest that uNK cell testing identifies those women at risk of reproductive
      failure due to relative uterine cortisol deficiency.

PMID- 24025401
TI  - Inhibition of hepatitis C virus infection by polyoxometalates.
AB  - Hepatitis C virus (HCV) infects about 2% of the world population. The standard
      treatment of chronic HCV infection is still discontented because of the low
      sustained virological response rate. The development of new HCV antivirals is a
      healthcare imperative. We explored the potentials of polyoxometalates to inhibit
      HCV infection using newly developed HCVcc cell culture system. We found one
      polyoxometalate compound (named POM-12) can inhibit HCV infection at the
      nanomolar range while displayed little cytotoxicity. We showed that POM-12
      inhibited pseudotyped HCV infection but had no effect on HCV RNA replication.
      Furthermore, we showed that POM-12 was virucidal and can disrupt HCV particles.
      Finally we demonstrated that POM-12 had no effect on the vesicular stomatitis
      virus infection while had weak inhibitory activity against the influenza virus
      infection. In conclusion, we identified a potent anti-HCV compound which may
      provide an attractive drug candidate to cure HCV infection. 

PMID- 24025404
TI  - Gastro 2013 and training center news.

PMID- 24025403
TI  - Participatory study of medicinal plants used in the control of gastrointestinal
      parasites in donkeys in Eastern Shewa and Arsi zones of Oromia region, Ethiopia.
AB  - BACKGROUND: Gastrointestinal nematode infections constitute a threat to the
      health and welfare of donkeys worldwide. Their primary means of control is via
      anthelmintic treatments; however, use of these drugs has constraints in
      developing countries, including cost, limited availability, access to cheaper
      generic forms of variable quality and potential anthelmintic resistance. As an
      alternative, bioactive plants have been proposed as an option to treat and
      control gastrointestinal helminths in donkeys. This study aimed to use
      participatory methodology to explore donkey owner knowledge, attitudes and
      beliefs relating to the use of plant-based treatments for gastrointestinal
      parasites of donkeys in Ethiopia. RESULTS: In focus groups, 22/29 groups stated
      they knew of plants used for the treatment of gastrointestinal parasites in
      donkeys. All groups volunteered plants that were used in cattle and/or small
      ruminants. In total, 21 plants were named by participants. 'Koso' (Hagenia
      abyssinica) 'Grawa' (Vernonia amygdalina) and a mixed roots and leaves
      preparation were the most frequently named plant preparations. 'Enkoko' (Embelia
      shimperi) and 'a mixture of roots and leaves' were ranked highly for
      effectiveness in donkeys. However, 'Grawa' and 'Koso' were the highest ranked
      when taking into account both the rank position and the number of groups ranking
      the plant.Thematic analysis of participants' current attitudes and beliefs
      surrounding traditional plant-based remedies for gastrointestinal parasites
      revealed that anthelmintics obtained from clinics were generally favoured due to
      their ease of administration and perceived higher effectiveness. There was doubt
      surrounding the effectiveness of some plant-based treatments, but there were also
      perceived advantages including their low cost, ease of cultivation and
      availability. However, plant-based treatments were considered a "past trend" and
      people favoured "modern" medicine, particularly among the younger generation.
      CONCLUSIONS: There was extensive knowledge of plant-based treatments for
      gastrointestinal parasites in livestock in Ethiopia. In donkeys, Koso (Hagenia
      abyssinica), Grawa (Vernonia amygdalina), Enkoko (Embelia shimperi) and 'mixed
      roots and leaves' were the most frequently named and/or highest ranked plants
      with reported efficacy against gastrointestinal parasites. Further in vitro and
      in vivo investigation of these plants is now required to determine viable
      alternatives for the treatment and control of gastrointestinal parasites in
      Ethiopia.

PMID- 24025402
TI  - An ENU mutagenesis screen identifies novel and  known genes involved in
      epigenetic processes in  the mouse.
AB  - BACKGROUND: We have used a sensitized ENU mutagenesis screen to produce mouse
      lines that carry mutations in genes required for epigenetic regulation. We call
      these lines Modifiers of murine metastable epialleles (Mommes). RESULTS: We
      report a basic molecular and phenotypic characterization for twenty of the Momme
      mouse lines, and in each case we also identify the causative mutation. Three of
      the lines carry a mutation in a novel epigenetic modifier, Rearranged L-myc
      fusion (Rlf), and one gene, Rap-interacting factor 1 (Rif1), has not previously
      been reported to be involved in transcriptional regulation in mammals. Many of
      the other lines are novel alleles of known epigenetic regulators. For two genes,
      Rlf and Widely-interspaced zinc finger (Wiz), we describe the first mouse
      mutants. All of the Momme mutants show some degree of homozygous embryonic
      lethality, emphasizing the importance of epigenetic processes. The penetrance of
      lethality is incomplete in a number of cases. Similarly ,abnormalities in
      phenotype seen in the heterozygous individuals of some lines occur with
      incomplete penetrance. CONCLUSIONS: Recent advances in sequencing enhance the
      power of sensitized mutagenesis screens to identify the function of previously
      uncharacterized factors and to discover additional functions for previously
      characterized proteins. The observation of incomplete penetrance of phenotypes in
      these inbred mutant mice, at various stages of development, is of interest.
      Overall, the Momme collection of mouse mutants provides a valuable resource for
      researchers across many disciplines.

PMID- 24025405
TI  - New exome data question the pathogenicity of genetic variants previously
      associated with catecholaminergic polymorphic ventricular tachycardia.
AB  - BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a
      lethal, rare hereditary disease with an estimated prevalence of 1:10 000. The
      genetic variants that cause CPVT are usually highly penetrant. To date, about 189
      variants in 5 genes (RYR2, CASQ2, CALM1, TRND, and KCNJ2) have been associated
      with CPVT pathogenesis. METHODS AND RESULTS: The Exome Sequencing Project
      database (ESP; n=6503) was systematically searched for previously published
      missense and nonsense CPVT-associated variants reported in several comprehensive
      reviews and in 2 databases: The Human Gene Mutation Database and The Inherited
      Arrhythmias Database. We used 4 different prediction tools to assess all missense
      variants previously associated with CPVT and compared the prediction of protein
      damage between CPVT-associated variants identified in the ESP and those variants
      not identified in the ESP. We identified 11% of the variants previously
      associated with CPVT in the ESP population. In the literature, 57% of these
      variants were reported as novel disease-causing variants absent in the healthy
      control subjects. These putative CPVT variants were identified in 41 out of 6131
      subjects in the ESP population, corresponding to a prevalence of CPVT of up to
      1:150. Using an agreement of >=3, in silico prediction tools showed a
      significantly higher frequency of damaging variants among the CPVT-associated
      variants not identified in the ESP database (83%) compared with those variants
      identified in the ESP (50%; P=0.021). CONCLUSIONS: We identified a substantial
      overrepresentation of CPVT-associated variants in a large exome database,
      suggesting that these variants are not necessarily the monogenic cause of CPVT.

PMID- 24025406
TI  - Exploring the unique features of the ARC channel, a store-independent Orai
      channel.
AB  - The discovery of the Orai proteins, and the identification of STIM1 as the
      molecule that regulates them, was based on their role in the agonist-activated
      store-operated entry of calcium via the CRAC channels. However, these same
      proteins are also essential components of the ARC channels responsible for a
      similar agonist-activated, but store-independent, arachidonic acid-regulated
      entry of calcium. The fact that these 2 biophysically similar calcium entry
      pathways frequently co-exist in the same cells suggests that they must each
      possess different features that allow them to function in distinct ways to
      regulate specific cellular activities. This review begins to address this
      question by describing recent findings characterizing the unique features of the
      ARC channels--their molecular composition, STIM1-dependent activation, and
      physiological activities--and the importance of defining such features for the
      accurate therapeutic targeting of these 2 Orai channel subtypes.

PMID- 24025408
TI  - Rotatable magnetic anisotropy in Si/SiO2/(Co2Fe)(x)Ge(1-x) Heusler alloy films.
AB  - Polycrystalline (Co2Fe)(x)Ge(1-x) Heusler alloy films are fabricated by
      sputtering on amorphous substrates and shown to possess three types of magnetic
      anisotropy. The nearly stoichiometric composition of x = 50 m.f.% shows a
      rectangular hysteresis loop and isotropic coercive and ferromagnetic resonance
      fields when the film is field-magnetized along any in-plane direction, thus
      predominantly possessing rotatable in-plane magnetic anisotropy. Higher-x
      compositions show evidence of two- and fourfold in-plane anisotropy superposed on
      the rotatable one. A qualitative model of the observed anisotropic magnetic
      properties is proposed. The model explains the rotatable anisotropy by taking
      into account dry friction for the in-plane rotation of the magnetization
      direction in a fine-grained polycrystalline film with the magnetic grain size
      smaller than the correlation length of the inter-grain exchange interaction. The
      observed two- and fourfold magnetic anisotropy contributions are attributed to
      partial texturing of the fine-grained films, even though the films are grown on
      amorphous SiO2 substrates. These results should be valuable for understanding and
      controlling the magnetic behaviour of highly spin-polarized Heusler alloy films
      used in various magnetic nanodevices.

PMID- 24025407
TI  - Leptin receptor maintains cancer stem-like properties in triple negative breast
      cancer cells.
AB  - Despite new therapies, breast cancer continues to be the second leading cause of
      cancer mortality in women, a consequence of recurrence and metastasis. In recent
      years, a population of cancer cells has been identified, called cancer stem cells
      (CSCs) with self-renewal capacity, proposed to underlie tumor recurrence and
      metastasis. We previously showed that the adipose tissue cytokine LEPTIN,
      increased in obesity, promotes the survival of CSCs in vivo. Here, we tested the
      hypothesis that the leptin receptor (LEPR), expressed in mammary cancer cells, is
      necessary for maintaining CSC-like and metastatic properties. We silenced LEPR
      via shRNA lentivirus transduction and determined that the expression of stem cell
      self-renewal transcription factors NANOG, SOX2, and OCT4 (POU5F1) is inhibited.
      LEPR-NANOG signaling pathway is conserved between species because we can rescue
      NANOG expression in human LEPR-silenced cells with the mouse LepR. Using a NANOG
      promoter GFP reporter, we showed that LEPR is enriched in NANOG promoter active
      (GFP+) cells. In lineage tracing studies, we showed that the GFP+ cells divide in
      a symmetric and asymmetric manner. LEPR-silenced MDA-MB-231 cells exhibit a
      mesenchymal to epithelial transition morphologically, increased E-CADHERIN and
      decreased VIMENTIN expression compared with control cells. Finally, LEPR-silenced
      cells exhibit reduced cell proliferation, self-renewal in tumor sphere assays,
      and tumor outgrowth in xenotransplant studies. Given the emergence of NANOG as a
      pro-carcinogenic protein in multiple cancers, these studies suggest that
      inhibition of LEPR may be a promising therapeutic approach to inhibit NANOG and
      thereby neutralize CSC functions.

PMID- 24025409
TI  - Treatment of agarose-agarose RENCA macrobeads with docetaxel selects for OCT4(+)
      cells with tumor-initiating capability.
AB  - The cancer stem cell (CSC) theory depicts such cells as having the capacity to
      produce both identical CSCs (symmetrical division) and tumor-amplifying daughter
      cells (asymmetric division). CSCs are thought to reside in niches similar to
      those of normal stem cells as described for neural, intestinal, and epidermal
      tissue, are resistant to chemotherapy, and are responsible for tumor recurrence.
      We recently described the niche-like nature of mouse renal adenocarcinoma (RENCA)
      cells following encapsulation in agarose macrobeads. In this paper we tested the
      hypothesis that encapsulated RENCA colonies function as an in vitro model of a
      CSC niche and that the majority of cells would undergo chemotherapy-induced
      death, followed by tumor recurrence. After exposure to docetaxel (5 ug/ml), 50%
      of cells were lost one week post-treatment while only one or two cells remained
      in each colony by 6 weeks. Surviving cells expressed OCT4 and reformed tumors at
      16 weeks post-treatment. Docetaxel-resistant cells also grew as monolayers in
      cell culture (16-17 weeks post-exposure) or as primary tumors following
      transplantation to Balb/c mice (6 of 10 mice) or NOD.CB17-Prkdc(scid)/J mice (9
      of 9 mice; 10 weeks post-transplantation or 28 weeks post-exposure). These data
      support the hypothesis that a rare subpopulation of OCT4(+) cells are resistant
      to docetaxel and these cells are sufficient for tumor recurrence. The reported
      methodology can be used to obtain purified populations of tumor-initiating cells,
      to screen for anti-tumor-initiating cell agents, and to investigate the in vitro
      correlate of a CSC niche, especially as it relates to chemo-resistance and tumor
      recurrence.

PMID- 24025410
TI  - Cancer mortality trends between 1988 and 2009 in the metropolitan area of Naples
      and Caserta, Southern Italy: Results from a joinpoint regression analysis.
AB  - Mortality data by geographic area and trend-based surveillance are particularly
      relevant in orienting public health decisions targeting specific populations. We
      analyzed overall and site-specific cancer mortality between 1988 and 2009 in the
      metropolitan area of Naples and Caserta in southern Italy. Age-standardized
      mortality rates (SMR) were computed for each 5-y age group, by gender, primitive
      cancer site and specific Province in the overall population and age-defined
      subgroups. Cancer mortality trends were quantified by annual percent change (APC)
      and 95% confidence interval (CI). From Naples and Caserta, the reduction observed
      between 1988 and 2009 in SMR in males, but not in females, was significantly
      lower compared with the decrease reported at a national level (-11.4% and -28.4%,
      respectively). In elderly men, differences between local and national SMR were
      more pronounced (+13.6% compared with -2.7%). In males, the joinpoint regression
      analysis showed the following APC and 95% CI: -0.9%/year (-1.2; -0.7) and 
      0.6%/year (-1.0; -0.2) for Naples and Caserta, respectively. In females,
      estimates were -0.6%/year (-0.8; -0.5) and -0.7%/year (-1.2; -0.3). The overall
      orientation toward declining cancer mortality trends appeared in antithesis with
      the slight, but significant, increase for some tumors (e.g., pancreatic cancer in
      both genders). A complex mixture of heterogeneous factors concurs to explain the
      evidence observed including lifestyle, access to screening procedures,
      advancements in cancer diagnosis and treatment. Further details might eventually
      derive from biomonitoring studies for ascertaining the causal link between
      exposure to potential contaminants in air, water, and soil and cancer-related
      outcomes in the area of interest.

PMID- 24025411
TI  - Advances in the understanding of the Fanconi anemia tumor suppressor pathway.
AB  - Extremely high cancer incidence in Fanconi anemia (FA) patients has long
      suggested that the FA signaling pathway is a tumor suppressor pathway. Indeed,
      our recent findings, for the first time, indicate that the FA pathway plays a
      significant role in suppressing the development of non-FA human cancer. Also our
      studies on FA group D2 protein (FANCD2) have, among the first, documented the
      crosstalks between the FA and Rad6/Rad18 (HHR6) pathways upon DNA damage. In this
      review, we will discuss how our studies enhance the understanding of the FA tumor
      suppressor pathway.

PMID- 24025412
TI  - Global analysis of serum microRNAs as potential biomarkers for lung
      adenocarcinoma.
AB  - Early diagnosis and the ability to predict the most relevant treatment option for
      individuals is essential to improve clinical outcomes for non-small cell lung
      cancer (NSCLC) patients. Adenocarcinoma (ADC), a subtype of NSCLC, is the single
      biggest cancer killer and therefore an urgent need to identify minimally invasive
      biomarkers to enable early diagnosis. Recent studies, by ourselves and others,
      indicate that circulating miRNAs have potential as biomarkers. Here we applied
      global profiling approaches in serum from patients with ADC of the lung to
      explore if miRNAs have potential as diagnostic biomarkers. This study involved
      RNA isolation from 80 sera specimens including those from ADC patients (equal
      numbers of stages 1, 2, 3, and 4) and age- and gender-matched controls (n = 40
      each). Six hundred and sixty-seven miRNAs were co-analyzed in these specimens
      using TaqMan low density arrays and qPCR validation using individual miRNAs.
      Overall, approximately 390 and 370 miRNAs were detected in ADC and control sera,
      respectively. A group of 6 miRNAs, miR-30c-1* (AUC = 0.74; P<0.002), miR-616*
      (AUC = 0.71; P = 0.001), miR-146b-3p (AUC = 0.82; P<0.0001), miR-566 (AUC = 0.80;
      P<0.0001), miR-550 (AUC = 0.72; P = 0.0006), and miR-939 (AUC = 0.82; P<0.0001)
      was found to be present at substantially higher levels in ADC compared with
      control sera. Conversely, miR-339-5p and miR-656 were detected at substantially
      lower levels in ADC sera (co-analysis resulting in AUC = 0.6; P = 0.02).
      Differences in miRNA profile identified support circulating miRNAs having
      potential as diagnostic biomarkers for ADC. More extensive studies of ADC and
      control serum specimens are warranted to independently validate the potential
      clinical relevance of these miRNAs as minimally invasive biomarkers for ADC.

PMID- 24025413
TI  - Single agent panitumumab in KRAS wild-type metastatic colorectal cancer patients
      following cetuximab-based regimens: Clinical outcome and biomarkers of efficacy.
AB  - BACKGROUND: Few data are available outlining outcomes of panitumumab in advanced
      colorectal cancer patients benefiting from prior cetuximab-based regimens.
      PATIENTS AND METHODS: Thirty patients with KRAS wild type metastatic colorectal
      cancer with clinical benefit from prior cetuximab-based regimens between May 2004
      and October 2011 were reviewed at nine Italian Institutions. Inclusion key
      criteria included interruption of cetuximab for reasons other than progressive
      disease. Patients were classified according to prior regimens (0 or >=1), prior
      response or stabilization, surgery of metastases, and Kohne prognostic score. At
      the time of subsequent progression, patients were treated with single agent
      panitumumab until progressive disease, unacceptable toxicity, or consent
      withdrawal. RESULTS: Panitumumab obtained 67% disease control rate and 30%
      objective response rate, with median PFS of 4.2 and median OS of 9.6 mo. Patients
      with BRAF/NRAS/PI3KCA and KRAS (by mutant enriched technique) wild-type tumors
      had the best chance of response to panitumumab. CONCLUSIONS: Single agent
      panitumumab provided significant clinical benefit in heavily pretreated patients
      without acquired resistance to prior cetuximab-based regimens.

PMID- 24025414
TI  - Therapy-related myeloid neoplasms after autologous hematopoietic stem cell
      transplantation in lymphoma patients.
AB  - Lymphoma patients treated with autologous transplantation (ASCT) live an
      increasingly long life with the recent advancement in therapeutic modalities.
      This has resulted in an increase in the incidence of therapy-related myeloid
      neoplasms (t-MN), which is one of the leading causes of non-relapse mortality.
      Several observational studies have linked the development of t-MN after ASCT with
      the intensity and frequency of chemotherapy, particularly alkylating agents, use
      of total body irradiation (TBI), and peripheral blood progenitor cells. In
      addition, role of genetic factors is increasingly being identified. It is
      postulated that the use of chemotherapy prior to ASCT results in DNA damage of
      progenitor cells, mitochondrial dysfunction, and altered gene expression related
      to DNA repair, metabolism as well as hematopoietic regulation. Cytogenetic
      studies have shown the presence of abnormalities in the peripheral blood
      progenitor cells prior to ASCT. It is, therefore, likely that the reinfusion of
      peripheral blood progenitor cells, proliferative stress on infused progenitor
      cells during hematopoietic regeneration and associated telomere shortening
      ultimately result in clonal hematopoiesis and blastic transformation. Cytopenias,
      myelodysplasia, or cytogenetic abnormalities are common and can be transient
      after ASCT; therefore, only when present together, they do confirm the diagnosis
      of t-MN. Attempts to reduce the occurrence of t-MN should be directed toward
      minimizing the exposure to the identified risk factors. Although the median
      survival is few months to less than a year, studies have shown the promising role
      of allogeneic transplantation in select young t-MN patients without high-risk
      cytogenetics. In this review we will explain the recent findings in the field of
      t-MN in lymphoma patients that have implications for identifying the molecular
      and genetic mechanisms of leukemogenesis and discuss potential strategies to
      reduce the risk of t-MN in this patient population.

PMID- 24025415
TI  - Chemotherapy agents-induced immunoresistance in lung cancer cells could be
      reversed by trop-2 inhibition in vitro and in vivo by interaction with MAPK
      signaling pathway.
AB  - Chemotherapy has been widely used in cancer treatment, but the prognosis of the
      cancer patients following chemotherapy has not been substantially improved.
      Alternative strategies such as immunotherapy and their combinations with
      chemotherapy are now being considered; however, the effects of chemotherapy on
      the immune responses of cancer cells are not fully understood. In the present
      studies, we reveal a potential link between chemotherapy and cancer
      immunoresistance, we first examined the effects of chemopreventive agent DDP on
      the expression of a cell surface glycopreotein Trop-2 in lung cancer cells, and
      found that DDP not only induce Trop-2 surface expression in human lung cancer
      cells, but also induce T-cell apoptosis effectively. In order to investigate the
      relationship between DDP-induced Trop-2 expression and T-cell apoptosis, we
      stably transfected A549 and PC14 lung cancer cells with Trop-2 shRNA, the DDP
      induced Trop-2 surface expression was effectively decreased in stably transfected
      cell lines, but chemotherapeutic reagent-induced cell proliferation inhibition
      and apoptosis were increased through inhibition of the MAPK signaling pathway. In
      vivo animal experiments showed that Trop-2 knockdown tumors displayed a slower
      growth rate than the control xenografts. Importantly, DDP treatment exhibited a
      strong antitumor activity in the mice with Trop-2 knockdown tumors, but only a
      marginal effect in the control group. Taken together, our data show that DDP
      resistance in lung cancer cells could be induced through increased surface
      expression of Trop-2, which at least partially by interfering with MAPK pathway.
      These results provide novel insight into the function of Trop-2 and encourage the
      design and testing of approaches targeting this protein and its partners.

PMID- 24025416
TI  - The S492R EGFR ectodomain mutation is never detected in KRAS wild-type colorectal
      carcinoma before exposure to EGFR monoclonal antibodies.
AB  - The activity of the epidermal growth factor receptor (EGFR) antibodies cetuximab
      and panitumumab in metastatic colorectal carcinoma (mCRC) is significantly
      limited by molecular mechanisms leading to intrinsic or acquired resistance. The
      S492R mutation of the EGFR, which is caused by either the 1476C>A or the 1474A>C
      substitution, interferes with binding to cetuximab but not to panitumumab, and
      has been detected in mCRC with acquired resistance to cetuximab. Since mechanisms
      of acquired and intrinsic resistance to EGFR monoclonal antibodies in CRC
      significantly overlap, we evaluated the frequency of the S492R mutation in a
      series of KRAS-exon 2 wild-type CRC patients. Genomic DNA was extracted from
      formalin fixed paraffin embedded (FFPE) tissues that were obtained from 505
      systemic therapy-naive CRC patients. A PCR/sequencing method for the detection of
      the S492R mutation was developed, by using as positive control a plasmid in which
      the 1474A>C mutation was generated by site directed mutagenesis. The lowest level
      of detection of this assay was approximately 10% mutant DNA in a background of
      wild-type DNA. PCR sequencing analysis revealed no S492R mutations in any of the
      analyzed 505 CRC specimens. Our findings suggest that the S492R mutation is not
      involved in primary resistance to cetuximab in CRC. Therefore, patients with mCRC
      should not be routinely screened for this mutation prior therapy with cetuximab.

PMID- 24025417
TI  - Diagnostic and prognostic value of plasma microRNA deregulation in nasopharyngeal
      carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is uncommon worldwide but often highly invasive in
      late stages. Due to its special location and lack of specific symptoms, NPC is
      hardly detected in regular medical examination at the beginning. Development of
      sensitive and specific biomarkers should help to save lives against this type of
      disease. In the present report, we investigated the value of plasma miRNAs for
      diagnosis and prognosis of NPC. Using candidate approach, we selected 21 miRNAs
      from literature to compare their expression levels in the plasma of NPC patients
      and controls. As a result, 5 miRNAs showed diagnostic potentials (P<0.01). Among
      them, miR-16, -21, -24, and -155 had increased levels in NPC patients, whereas
      the level of miR-378 was decreased. There was a negative correlation between
      plasma miRNA expression and cancer progression, where miR-21 was statistically
      significant in T and N staging and miR-16 and 24 were significant in N staging
      only. Combination of miR-16, -21, -24, -155, and -378 gives 87.7% of sensitivity
      and 82.0% of specificity for NPC diagnosis. Without miR-16, combination of the
      rest 4 miRNAs gives the same sensitivity but a slightly reduced specificity.
      After treatment, all 5 miRNAs were somewhat back to normal levels in patients
      without cancer recurrence but the prognostic value was not statistically
      significant. In conclusion, plasma miRNA expression is a useful biomarker for NPC
      diagnosis but not for its prognosis. More importantly, it is simple, effective,
      and non-invasive. Combination of several plasma miRNAs can increase both NPC
      diagnostic sensitivity and specificity.

PMID- 24025418
TI  - miR-34a suppresses mutagenesis by inducing apoptosis in human lymphoblastoid TK6
      cells.
AB  - miR-34a, a tumor suppressor miRNA, has been identified as a direct
      transcriptional target of P53. miRNA precursors and inhibitors have been used to
      modulate the expression of their targeted mRNA and thereby study miRNA functions.
      We indicated in our previous work that X-ray induces miR-34a expression in a time
      and dose dependent manner. The objective of this study was to elucidate the role
      of miR-34a in X-ray-induced mutations in human lymphoblast TK6 cells. Neither
      over-expression of miR-34a by lipid transfection of miR-34a precursor nor down
      regulation of endogenous miR-34a by miR-34a inhibitor had any effect on X-ray
      induced micronucleus frequency in TK6 cells. Over-expression of miR-34a in TK6
      cells significantly reduced X-ray induced mutant frequency (MF) in the Thymidine
      Kinase (TK) locus while suppression of endogenous miR-34a can increase the
      background level MF in TK6 cells. Furthermore, over-expression of miR-34a
      promoted and down-regulation of miR-34a inhibited background and X-ray-induced
      apoptosis in TK6 cells. Our study suggests miR-34a is an important negative
      regulator of mutagenesis and the mechanism is possibly mediated through
      apoptosis. 

PMID- 24025419
TI  - Health-related quality of life in pediatric liver transplanted patients compared
      with a chronic liver disease group.
AB  - BACKGROUND: Achieving a good health-related quality of life (HRQoL) is currently
      one of the main aims in long term survival of liver transplanted children (PLT).
      Purpose of our study is to compare HRQoL of PLT patients (N = 33, mean age 12.8
      y) vs. sex and age matched patients with compensated and clinically stable
      chronic liver disease (CLD) (N = 25, mean age 11.9 y). METHODS: HRQoL was
      measured from both patient and parental perspectives using the CHQ-CF87 and CHQ
      PF50 questionnaires, respectively. RESULTS: General Health Perception scores of
      PLT subjects resulted significantly lower than those of CLD both at self- and
      parental report (p < 0.05 and p < 0.01, respectively). No other significant
      differences in other HRQoL domains were found between groups. CONCLUSION: Our
      results suggest that the two populations are quite similar regarding HRQoL, but
      both parents and children of PLT group perceive a worse general health. Further
      studies are needed to confirm these results.

PMID- 24025420
TI  - Distribution of alpha thalassaemia gene variants in diverse ethnic populations in
      malaysia: data from the institute for medical research.
AB  - Alpha thalassaemia is highly prevalent in the plural society of Malaysia and is a
      public health problem. Haematological and molecular data from 5016 unrelated
      patients referred from various hospitals to the Institute for Medical Research
      for alpha thalassaemia screening from 2007 to 2010 were retrieved. The aims of
      this retrospective analysis were to describe the distribution of various alpha
      thalassaemia alleles in different ethnic groups, along with their genotypic
      interactions, and to illustrate the haematological changes associated with each
      phenotype. Amongst the patients, 51.2% (n = 2567) were diagnosed with alpha
      thalassaemia. Of the 13 alpha thalassaemia determinants screened, eight different
      deletions and mutations were demonstrated: three double gene deletions, --(SEA), 
      -(THAI), --(FIL); two single-gene deletions, alpha-3.7 and -alpha4.2; and three
      non-deletion mutations, Cd59G > A (haemoglobin [Hb] Adana), Cd125T > C (Hb Quong
      Sze) and Cd142 (Hb Constant Spring). A high incidence of alpha-3.7 deletion was
      observed in Malays, Indians, Sabahans, Sarawakians and Orang Asli people.
      However, the --SEA deletion was the most common cause of alpha thalassaemia in
      Chinese, followed by the alpha-3.7 deletion. As many as 27 genotypic interactions
      showed 1023 alpha thalassaemia silent carriers, 196 homozygous alpha+
      thalassaemia traits, 973 heterozygous alpha0 thalassaemia carriers and 375
      patients with Hb H disease. Statistical analysis showed a significant difference
      in the distribution of alpha thalassaemia determinants amongst the various ethnic
      groups. Hence, the heterogeneous distribution of common determinants indicated
      that the introduction of an ethnicity-targeted hierarchical alpha thalassaemia
      screening approach in this multi-ethnic Malaysian population would be effective.

PMID- 24025421
TI  - Molecular cloning and functional analysis of the duck TLR4 gene.
AB  - Toll-like receptor 4 (TLR4) recognizes pathogen-associated molecular patterns in
      some animals and has been shown to be closely associated with several diseases
      such as tumors, atherosclerosis, and asthma. However, its function in ducks is
      not clear. Alternative splicing of the TLR4 gene has been identified in pigs,
      sheep, mice, and other species, but has not yet been reported in the duck. In
      this study, alternative splicing of the duck TLR4 gene was investigated using
      reverse transcription-polymerase chain reaction (RT-PCR). Duck TLR4 gene (duTLR4,
      accession number: KF278109) was found to consist of 3367 nucleotides of coding
      sequence. An alternative splice form, TLR4-b, was identified and shown by
      alignment to retain the intron between exons 1 and 2. Real-time quantitative
      polymerase chain reaction (qPCR) analyses suggested that duTLR4-a (wild-type)
      mRNA is widely expressed in various healthy tissues, whereas TLR4-b is expressed
      at only low levels. Following stimulation of normal duck embryo fibroblasts with
      lipopolysaccharide, the expression of both isoforms initially increased and then
      decreased. Expression of the wild-type isoform subsequently increased again,
      while that of the variant remained low. The expression levels of wild-type TLR4
      were further analyzed by transient transfection of a pcDNA3.1(+)-TLR4-a
      overexpression vector into duck embryo fibroblasts. qRT-PCR analyses showed that
      after stimulation with LPS and poly(I:C) the expression levels of IL-1beta, IL6,
      and MHC II increased with a response-efficacy relationship. Our experimental
      results indicate that TLR4 plays an important role in resistance to both
      bacterial and viral infections in the duck. 

PMID- 24025422
TI  - High-level overproduction of Thermobifida enzyme in Streptomyces lividans using a
      novel expression vector.
AB  - In this study, we constructed a novel Streptomyces-E.coli shuttle vector pZRJ362
      combining the xylose isomerase promoter and amylase terminator. A gene encoding
      the endoglucanase Cel6A in Thermobifida fusca was amplified by PCR, cloned into
      Streptomyces lividans host strain using the novel expression vector and Pichia
      pastoris GS115 host strain using the vector pPICZalpha-C, respectively.
      Afterwards, the expression pattern and the maximum expression level were
      comparatively studied in both expression systems. The maximum enzyme activity of
      Cel6A-(His)6 secreted in S. lividans supernatant after 84-h of cultivation
      amounted to 5.56 U/mL, which was dramatically higher than that secreted in P.
      pastoris about 1.4 U/mL after 96-h of cultivation. The maximum expression level
      of Cel6A-(His)6 in S. lividans supernatant reached up to 173 mg/L after 84-h of
      cultivation. The endoglucanase activity staining SDS-PAGE showed that there were
      some minor proteins in S. lividans supernatant which may be the Cel6A derivant by
      proteolytic degradation, while there was no proteolytic product detected in
      supernatant of P. pastoris.

PMID- 24025423
TI  - Redox signaling is an early event in the pathogenesis of renovascular
      hypertension.
AB  - Activation of the renin-angiotensin-aldosterone system plays a critical role in
      the development of chronic renal damage in patients with renovascular
      hypertension. Although angiotensin II (Ang II) promotes oxidative stress,
      inflammation, and fibrosis, it is not known how these pathways intersect to
      produce chronic renal damage. We tested the hypothesis that renal parenchymal
      cells are subjected to oxidant stress early in the development of RVH and produce
      signals that promote influx of inflammatory cells, which may then propagate
      chronic renal injury. We established a reproducible murine model of RVH by
      placing a tetrafluoroethylene cuff on the right renal artery. Three days after
      cuff placement, renal tissue demonstrates no histologic abnormalities despite up
      regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed
      after seven days and was associated with induction of Tnfalpha and influx of CD3+
      T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal
      atrophy with interstitial inflammation and fibrosis, despite normalization of
      plasma renin activity. Based on these considerations, we propose that renal
      parenchymal cells initiate a progressive cascade of events leading to oxidative
      stress, interstitial inflammation, renal fibrosis, and atrophy.

PMID- 24025424
TI  - Neuroprotective effect of arctigenin via upregulation of P-CREB in mouse primary
      neurons and human SH-SY5Y neuroblastoma cells.
AB  - Arctigenin (Arc) has been shown to act on scopolamine-induced memory deficit mice
      and to provide a neuroprotective effect on cultured cortical neurons from
      glutamate-induced neurodegeneration through mechanisms not completely defined.
      Here, we investigated the neuroprotective effect of Arc on H89-induced cell
      damage and its potential mechanisms in mouse cortical neurons and human SH-SY5Y
      neuroblastoma cells. We found that Arc prevented cell viability loss induced by
      H89 in human SH-SY5Y cells. Moreover, Arc reduced intracellular beta amyloid
      (Abeta) production induced by H89 in neurons and human SH-SY5Y cells, and Arc
      also inhibited the presenilin 1(PS1) protein level in neurons. In addition,
      neural apoptosis in both types of cells, inhibition of neurite outgrowth in human
      SH-SY5Y cells and reduction of synaptic marker synaptophysin (SYN) expression in
      neurons were also observed after H89 exposure. All these effects induced by H89
      were markedly reversed by Arc treatment. Arc also significantly attenuated
      downregulation of the phosphorylation of CREB (p-CREB) induced by H89, which may
      contribute to the neuroprotective effects of Arc. These results demonstrated that
      Arc exerted the ability to protect neurons and SH-SY5Y cells against H89-induced
      cell injury via upregulation of p-CREB. 

PMID- 24025425
TI  - Human diseases associated with form and function of the Golgi complex.
AB  - The Golgi complex lies at the heart of the secretory pathway and is responsible
      for modifying proteins and lipids, as well as sorting newly synthesized molecules
      to their correct destination. As a consequence of these important roles, any
      changes in its proteome can negatively affect its function and in turn lead to
      disease. Recently, a number of proteins have been identified, which when either
      depleted or mutated, result in diseases that affect various organ systems. Here
      we describe how these proteins have been linked to the Golgi complex, and
      specifically how they affect either the morphology, membrane traffic or
      glycosylation ability of this organelle. 

PMID- 24025426
TI  - An unexpectedly lichenase-stable hexasaccharide from cereal, horsetail and lichen
      mixed-linkage beta-glucans (MLGs): implications for MLG subunit distribution.
AB  - Mixed-linkage (1->3),(1->4)-beta-d-glucan (MLG) is a biologically and
      technologically important hemicellulose, known to occur in three widely separated
      lineages: the Poales (including grasses and cereals), Equisetum (fern-allies),
      and some lichens e.g. Iceland moss (Cetraria islandica). Lichenase (E.C.
      3.2.1.73) is widely assumed to hydrolyse all (1->4) bonds that immediately follow
      (1->3) bonds in MLG, generating predominantly the tetrasaccharide beta-d-Glcp-(1
      >4)-beta-d-Glcp-(1->4)-beta-d-Glcp-(1->3)-d-Glc (G4G4G3G; MLG4), the
      corresponding trisaccharide (G4G3G; MLG3), and sometimes also laminaribiose (G3G;
      MLG2). The ratio of the oligosaccharides produced characterises each
      polysaccharide. We report here that digestion of MLG from barley (Hordeum
      vulgare), Equisetum arvense and C. islandica by Bacillus subtilis lichenase also
      yields the unexpectedly stable hexasaccharide, beta-d-Glcp-(1->3)-beta-d-Glcp-(1
      >4)-beta-d-Glcp-(1->4)-beta-d-Glcp-(1->4)-beta-d-Glcp-(1->3)-d-Glc (G3G4G4G4G3G,
      i.e. MLG2-MLG4), identified by thin-layer chromatography, gel-permeation
      chromatography, HPLC (HPAEC), beta-glucosidase digestion, (1)H/(13)C-NMR
      spectroscopy and mass spectrometry. On HPLC, G3G4G4G4G3G is the major constituent
      of a peak previously ascribed solely to the nonasaccharide G4G4G4G4G4G4G4G3G.
      Because it was widely presumed that lichenase would cleave G3G4G4G4G3G to
      MLG2+MLG4, our data both redefine the substrate specificity of Bacillus lichenase
      and show previous attempts to characterise MLGs by HPLC of lichenase-digests to
      be flawed. MLG2 subunits are particularly underestimated; often reported as
      negligible, they are here shown to be an appreciable constituent of MLGs from all
      three lineages. We also show that there is no appreciable yield of water-soluble
      lichenase products with DP>9; potential identities of products previously
      labelled DP>9 are suggested. Finally, this discovery also provides a opportunity
      to investigate the spatial distribution of subunits along the MLG chain. We show
      that MLG2 subunits in barley and Cetraria MLG are not randomly distributed, but
      predominantly found at the non-reducing end of MLG4 subunits. 

PMID- 24025427
TI  - CD31 expression on peripheral blood stem cells predicts both early neutrophil and
      platelet engraftments.
AB  - No detailed information currently exists about the immune phenotypic profiles of
      peripheral blood stem cells (PBSCs) obtained by different mobilization regimens.
      The effects of these profiles on the outcome of transplantation are largely
      unknown. In this prospective study, the surface immune phenotypic features
      (CD11a, CD18, CD31, CD38, CD44, CD62e, CD62L, CD90, CD117, CD135 and CD184
      expression) of sorted PBSCs that had been mobilized by growth factor with (group
      I and group II) or without (group III) disease-specific chemotherapies were
      investigated. The immune phenotypic features on mobilized PBSCs in groups I, II
      and III were not significantly different. The CD31 (platelet endothelial cell
      adhesion molecule-1) positivity ratio on PBSCs inversely correlated with both the
      duration of neutrophil (r=-0.32, p=0.03) and platelet (r=-0.36, p=0.02)
      engraftment. No relationship was found between the engraftment (neutrophil and
      platelet) durations and CD184 (chemokine receptor CXC motif receptor 4 [CXCR4])
      expression on PBSCs. We demonstrated that the surface immune phenotypic profiles
      on PBSCs obtained by several mobilization regimens were not different. To our
      knowledge, this is the first study to demonstrate that CD31 expression on human
      PBSCs may positively affect both neutrophil and platelet engraftment. Contrary to
      our expectations, CD184 (CXCR4) expression on PBSCs has no effect on neutrophil
      or platelet engraftment. Considered together, our results suggest that additional
      surface antigens (such as CD31) may be more effective in the homing process.

PMID- 24025429
TI  - Interventions for supporting nurse retention in rural and remote areas: an
      umbrella review.
AB  - CONTEXT: Retention of nursing staff is a growing concern in many countries,
      especially in rural, remote or isolated regions, where it has major consequences
      on the accessibility of health services. PURPOSE: This umbrella review aims to
      synthesize the current evidence on the effectiveness of interventions to promote
      nurse retention in rural or remote areas, and to present a taxonomy of potential
      strategies to improve nurse retention in those regions. METHODS: We conducted an
      overview of systematic reviews, including the following steps: exploring
      scientific literature through predetermined criteria and extracting relevant
      information by two independents reviewers. We used the PRISMA (Preferred
      Reporting Items for Systematic reviews and Meta-Analyses) criteria in order to
      assess the quality of the reports. FINDINGS: Of 517 screened publications, we
      included five reviews. Two reviews showed that financial-incentive programs have
      substantial evidence to improve the distribution of human resources for health.
      The other three reviews highlighted supportive relationships in nursing,
      information and communication technologies support and rural health career
      pathways as factors influencing nurse retention in rural and remote areas.
      Overall, the quality of the reviews was acceptable. CONCLUSIONS: This overview
      provides a guide to orient future rural and remote nurse retention interventions.
      We distinguish four broad types of interventions: education and continuous
      professional development interventions, regulatory interventions, financial
      incentives, and personal and professional support. More knowledge is needed
      regarding the effectiveness of specific strategies to address the factors known
      to contribute to nurse retention in rural and remote areas. In order to ensure
      knowledge translation, retention strategies should be rigorously evaluated using
      appropriate designs.

PMID- 24025430
TI  - Inhibition of gustatory plasticity due to acute nicotine exposure in the nematode
      Caenorhabditis elegans.
AB  - The present study investigated the effect of nicotine exposure on gustatory
      plasticity in the nematode Caenorhabditis elegans. The chemotactic response of
      wild-type N2 nematodes pre-exposed to 100mM NaCl with 3.0mM nicotine was almost
      the same as that of mock-conditioned nematodes unexposed to NaCl; however, the
      response of N2 nematodes pre-exposed to NaCl without nicotine was significantly
      lower than that of mock-conditioned nematodes. These results indicate that
      gustatory plasticity is inhibited by acute nicotine exposure. Inhibition of
      gustatory plasticity was observed when cat-2 mutants with a defect in dopamine
      biosynthesis were pre-exposed to NaCl with 3.0mM nicotine. Acute nicotine
      exposure did not cause inhibition of gustatory plasticity in bas-1 mutants, which
      had defects in both serotonin and dopamine secretion, and tph-1 mutants, which
      had a defect in serotonin secretion only. However, inhibition of gustatory
      plasticity was observed when bas-1 and tph-1 mutants were maintained on a growth
      plate that included serotonin. These results suggest that serotonin signaling
      plays an essential role in the modulation of the acute effects of nicotine. 

PMID- 24025428
TI  - Assembly of a phased diploid Candida albicans  genome facilitates allele-specific
      measurements  and provides a simple model for repeat and indel  structure.
AB  - BACKGROUND: Candida albicans is a ubiquitous opportunistic fungal pathogen that
      afflicts immunocompromised human hosts. With rare and transient exceptions the
      yeast is diploid, yet despite its clinical relevance the respective sequences of
      its two homologous chromosomes have not been completely resolved. RESULTS: We
      construct a phased diploid genome assembly by deep sequencing a standard
      laboratory wild-type strain and a panel of strains homozygous for particular
      chromosomes. The assembly has 700-fold coverage on average,allowing extensive
      revision and expansion of the number of known SNPs and indels. This phased genome
      significantly enhances the sensitivity and specificity of allele-specific
      expression measurements by enabling pooling and cross-validation of signal across
      multiple polymorphic sites. Additionally, the diploid assembly reveals pervasive
      and unexpected patterns in allelic differences between homologous chromosomes.
      Firstly, we see striking clustering of indels, concentrated primarily in the
      repeat sequences in promoters. Secondly, both indels and their repeat-sequence
      substrate are enriched near replication origins. Finally, we reveal an intimate
      link between repeat sequences and indels, which argues that repeat length is
      under selective pressure for most eukaryotes. This connection is described by a
      concise one-parameter model that explains repeat-sequence abundance in C.
      albicans as a function of the indel rate,and provides a general framework to
      interpret repeat abundance in species ranging from bacteria to humans.
      CONCLUSIONS: The phased genome assembly and insights into repeat plasticity will
      be valuable for better understanding allele-specific phenomena and genome
      evolution.

PMID- 24025432
TI  - Impact of amino acid substitutions in two functional domains of Ku80: DNA-damage
      sensing ability of Ku80 and survival after irradiation.
AB  - Various chemotherapeutic drugs, such as etoposide, and ionizing radiation (IR)
      have been clinically applied for the treatment of many types of animal and human
      malignancies. IR and chemotheraputic drugs kill tumor cells mainly by inducing
      DNA double-strand breaks (DSBs). On the other hand, unrepaired or incorrectly
      repaired DSBs can lead to chromosomal truncations and translocations, which can
      contribute to the development of cancer in humans and animals. Thus, it is
      important to clarify the molecular mechanisms underlying the chemosensitivity or
      radiosensitivity of mammalian cells in order to develop medical treatments and
      next-generation chemotherapeutic drugs for cancer. Previously, we established and
      analyzed cell lines stably expressing chimeric constructs of EGFP and the wild
      type Ku80 (XRCC5) protein or its mutant protein to which mutations were
      introduced by the site-directed mutagenesis. We found that the Ku70 (XRCC6)
      binding-site mutations (A453H/V454H) of Ku80 and nuclear localization signal
      (NLS)-dysfunctional mutations (K565A/K566A/K568A) affected the ability to
      complement etoposide sensitivity. In this study, we examined the radiosensitivity
      of these cell lines. We found that either or both amino acid substitutions in two
      functional domains of Ku80, i.e., Ku70-binding-site mutations (A453H/V454H) and
      NLS-dysfunctional mutations (K565A/K566A/K568A), affect the ability to complement
      radiosensitivity. Moreover, these mutations in the two domains of Ku80 affect the
      DSB-sensing ability of Ku80. These information and Ku80 mutant cell lines used
      might be useful for the study of not only the dynamics and function of Ku80, but
      also the molecular mechanism underlying the cellular response to IR and
      chemotherapeutic drugs in mammalian cells. 

PMID- 24025431
TI  - GDNF induces synaptic vesicle markers in enteric neurons.
AB  - Regulation of intestinal motility depends on an intact synaptic vesicle
      apparatus. Thus, we investigated the expression of the synaptic vesicle markers
      synaptophysin and synaptobrevin in the human enteric nervous system (ENS) and
      their regulation by glial cell line-derived neurotrophic factor (GDNF) in
      cultured enteric neurons. Full-thickness specimens of the human colon were
      assessed for expression of synaptophysin and synaptobrevin and neuronal
      localization was assessed by dual-label immunocytochemistry with PGP 9.5. Effects
      of GDNF on both synaptic markers were monitored in enteric nerve cell cultures
      and the presence of varicosities was determined by applying electron microscopy
      to the cultures. Human colonic specimens showed immunoreactivity for
      synaptophysin and synaptobrevin in both myenteric and submucosal ganglia as well
      as in nerve fibers. Both synaptic vesicle markers co-localized with the neuronal
      marker PGP 9.5 and exhibited granular accumulation patterns in the human and rat
      ENS. In cultured rat myenteric neurons GDNF treatment promoted expression of both
      synaptic vesicle markers and the formation of neuronal varicosities. The
      regulation of synaptophysin and synaptobrevin in enteric neurons by GDNF argues
      for the induction of functional neuronal networks in culture characterized by an
      increase of synaptogenesis. 

PMID- 24025433
TI  - A case report of feline pituitary carcinoma with hypercortisolism.
AB  - Feline pituitary tumors are rare. An 8-year-old male Japanese domestic cat
      presented with anorexia and emaciation. The cat died 17 days after admission from
      progressive neurological symptoms. At necropsy, a pituitary tumor measuring 25 *
      18 * 15 mm was found. Microscopically, the tumor was divided into multiple
      lobules and had grown invasively into the adjacent brain tissue and sphenoid
      bone. Tumor cells had pleomorphic nuclei with prominent centrally located
      nucleoli and abundant amphophilic polygonal cytoplasm. Immunohistochemically, the
      tumor cells stained with anti-adrenocorticotropic hormone (ACTH), alpha-melanin
      stimulating hormone (MSH) and beta-endorphin antibodies. Ultrastructurally, the
      cytoplasm of the tumor cells contained various sized secretory granules. Based on
      these pathological findings, this tumor was diagnosed as pituitary carcinoma
      originated from pars intermedia cells. 

PMID- 24025434
TI  - Validity and suitability of the Bayley-III Low Motor/Vision version: a
      comparative study among young children with and without motor and/or visual
      impairments.
AB  - The aim of the present study was to examine the validity of the Bayley-III Low
      Motor/Vision version, and its suitability for children with motor and/or visual
      impairment(s). This version contains accommodated items, that is, adaptations to
      minimize impairment bias, without altering what the test measures. We
      hypothesized that the accommodations would not affect the item scores of children
      without impairment, and that children with impairment(s) would benefit from the
      accommodations. We tested 41 children without impairment and 63 children with
      impairment with both the standard Bayley-III and the Low Motor/Vision versions,
      in randomly counterbalanced order. The test administrators filled in an
      evaluation form. Results showed that the accommodations did not affect the test
      scores of children without impairment and did improve the test scores of children
      with impairment on the Cognition scale, while no improvement was found for the
      other scales. The test administrators indicated that the vast majority of the
      children with impairment had been able to show their abilities on the test and
      that the accommodations were beneficial in 29 out of these 52 cases. For some
      children, the accommodated instrument appeared to be unsuitable because the
      impairment was too severe. The conclusion is that the accommodations improve the
      validity of the Bayley-III when used with children with mild to moderate motor
      and/or visual impairment, especially with regard to the Cognition scale. 

PMID- 24025435
TI  - Enumeration skills in Down syndrome.
AB  - Individuals with Down syndrome (DS) exhibit various math difficulties which can
      be ascribed both to global intelligence level and/or to their atypical cognitive
      profile. In this light, it is crucial to investigate whether DS display deficits
      in basic numerical skills. In the present study, individuals with DS and two
      groups of typically developing (TD) children matched for mental and chronological
      age completed two delayed match-to-sample tasks in order to evaluate the
      functioning of visual enumeration skills. Children with DS showed a specific
      deficit in the discrimination of small numerosities (within the subitizing range)
      with respect to both mental and chronological age matched TD children. In
      contrast, the discrimination of larger numerosities, though lower than that of
      chronological age matched controls, was comparable to that of mental age matched
      controls. Finally, counting was less fluent but the understanding of cardinality
      seemed to be preserved in DS. These results suggest a deficit of the object
      tracking system underlying the parallel individuation of small numerosities and a
      typical - but developmentally delayed - acuity of the approximate number system
      for discrimination of larger numerosities. 

PMID- 24025436
TI  - Staff members of community services for people with intellectual disability and
      severe mental illness: values, attitudes, and burnout.
AB  - The study focused on the connections between the value preferences, attitudes
      toward community living, and burnout among staff members of community services
      for people with intellectual disability (n=126) and severe mental illness (n=96)
      in Israel. A higher preference for the self-transcendence values and a lower
      preference for the self-enhancement values were associated with the staff
      members' positive attitudes toward their clients' empowerment, a higher sense of
      similarity, and a negative attitude toward exclusion. In addition, a higher
      preference for the self-transcendence values and a lower preference for the self
      enhancement values were associated with a lower level of depersonalization and a
      higher sense of professional accomplishment. Finally, a more positive attitude
      toward empowerment, a higher sense of similarity, and a more negative attitude
      toward exclusion were associated with a lower level of burnout. 

PMID- 24025437
TI  - Sequential aiming movements and the one-target advantage in individuals with Down
      syndrome.
AB  - Research has revealed that individuals with Down syndrome (DS) have elevated
      reaction times, longer movement times, and greater movement errors during single
      target single-limb actions compared to their typically developing (TD) peers.
      These perceptual-motor impairments have been attributed to both central processes
      and the physical phenotype associated with DS. The purpose of the present study
      was to directly investigate these possible central and peripheral deficits by
      examining how individuals with DS plan and execute more complex movements. Three
      groups (DS, TD, and individuals with an undifferentiated intellectual disability;
      UID) of 8 participants completed a single target movement, a two-target movement
      performed by a single arm, and a two-target movement where the first movement was
      performed with one arm and the second movement performed with the other arm. For
      all groups and all conditions, movement times revealed a one-target advantage
      (OTA). Specifically, times to the first target were longer in the two-target
      responses compared to the single-target response. In general, the OTA finding
      reveals that persons with DS utilise planning strategies similar to their TD
      peers when performing sequential actions involving two targets and two arms.
      Furthermore, because the OTA was observed in both the single- and two-arm two
      target responses the interference in movement one associated with having to make
      a subsequent movement is not due to peripheral processes associated with single
      limb constraints. Rather, individuals with DS treat movements within a sequence
      as functionally dependent. Thus, the central processes associated with timing the
      implementation of the second element of the movement appear to be responsible for
      the interference that leads to the OTA.

PMID- 24025438
TI  - Predictors for changes in various developmental outcomes of children with
      cerebral palsy--a longitudinal study.
AB  - We aimed to identify predictors for the changes of various developmental outcomes
      in preschool children with cerebral palsy (CP). Participants were 78 children (49
      boys, 29 girls) with CP (mean age: 3 years, 8 months; SD: 1 year, 7 months;
      range: 1 year to 5 years, 6 months). We examined eight potential predictors: age,
      sex, CP subtype, Gross Motor Function Classification System (GMFCS) level,
      selective motor control, Modified Ashworth Scale, and the spinal alignment (SA)
      and range of motion subscales of the Spinal Alignment and Range of Motion Measure
      (SAROMM). Developmental outcomes for cognition, language, self-help, and social
      and motor functions were measured at baseline and a 6-month follow-up with the
      Comprehensive Developmental Inventory for Infants and Toddlers. Regression model
      showed GMFCS level was a negative predictor for change of language (adjusted
      r(2)=0.30, p<.001), motor function (adjusted r(2)=0.26, p<.001), social function
      (adjusted r(2)=0.07, p=0.014), and self-help (adjusted r(2)=0.26, p<.001). Age
      was a negative predictor for change of cognition (adjusted r(2)=0.21, p<.001) and
      language functions (adjusted r(2)=0.26, p<.001). SAROMM-SA was a negative
      predictor for cognitive change (adjusted r(2)=0.30, p<.001). The GMFCS levels and
      age are robust negative predictors for change of most developmental domains in
      these children. 

PMID- 24025439
TI  - Requirements for and impact of a serious game for neuro-pediatric robot-assisted
      gait training.
AB  - We investigated whether children with neurological gait disorders who walked in a
      driven gait orthosis could adjust their participation level according to the
      demands of a newly developed rehabilitation game. We further investigated if
      cognitive capacity and motor impairment influenced game performance. Nineteen
      children with neurological gait disorders (mean age: 13.4 y, 42% girls)
      participated. To quantify game participation, electromyographic muscle activity
      (M. rectus femoris) and heart rate were compared in a demanding part and a less
      demanding part of the game. Cognitive capacity was assessed with the Test of
      Nonverbal Intelligence (TONI-4). Furthermore, the Functional Independence Measure
      for Children (WeeFIM), Manual Muscle Tests and a therapist-derived score of how
      well the child was able to train were assessed. Results showed that muscle
      activity and heart rate were higher during the demanding part of the game (30.7
      +/- 22.6 MUV; 129.4 +/- 15.7 bpm) compared to the less demanding part (16.0 +/-
      13.4 MUV; 124.1 +/- 15.9 bpm; p<0.01 for both measures). Game performance
      correlated moderately with the TONI-4 (r=0.50, p=0.04) and the cognition subscale
      of the WeeFIM (rho=0.59, p=0.01). The therapist-derived score correlated
      significantly with game performance (p=0.75, p<0.01) and the ability to modify
      muscle activity to the demands of the game (p=-0.72, p<0.01). Receiver operating
      characteristic analyses revealed that the latter factor differentiated well
      between those children suitable for the game and those not. We conclude that
      children with neurological gait disorders are able to modify their activity to
      the demands of the VR-scenario. However, cognitive function and motor impairment
      determine to which extent. These results are important for clinical decision
      making.

PMID- 24025440
TI  - Initiatives to reduce the use of seclusion and restraints on people with
      developmental disabilities: a systematic review and quantitative synthesis.
AB  - Contrary to the expectations articulated in public policy, restrictive
      interventions are commonly used in support services for people with developmental
      disabilities. This systematic review and quantitative synthesis was undertaken to
      investigate whether the use of seclusion and restraints on people with
      developmental disabilities can be reduced. Searches of the Academic Search
      Complete, CINAHL, MEDLINE, and PsycINFO electronic databases returned 7226
      records, of which 11 met the inclusion criteria for this review. A further 3
      papers were obtained through scanning the reference lists of those articles
      included from the initial literature search. All 14 studies were single-subject
      designs focusing on initiatives to reduce physical or mechanical restraint.
      Between the baseline and intervention phases, there were mean reductions in the
      frequency and duration of restraint use of 79% (SD=21%, n=13 subjects from 7
      studies) and 45% (SD=58%, n=10 subjects from 6 studies), respectively. For
      studies in which restraint use to manage agitation and aggression was targeted,
      there was a 79% (SD=21%, n=13 subjects from 7 studies) decrease in the frequency
      and a 28% (SD=67%, n=6 subjects from 3 studies) reduction in the duration of
      restraint. With respect to studies in which restraint use to prevent self-harm
      was targeted, there was a 71% (SD=34%, n=4 subjects from 3 studies) reduction in
      restraint use. Effect sizes were calculable, using non-overlap approaches, for 9
      of the 14 studies. The magnitudes of the effect sizes suggest that, on average,
      the interventions were effective in reducing the use of restraints. The effects
      generated in studies where restraint use for self-harm was targeted were
      typically more pronounced than those in which restraint use for agitation and
      aggression was addressed. There were broad variations, however, in the percentage
      reductions in restraint use and in the magnitudes of the effect sizes. Although
      the findings of this review are encouraging, more research is needed, in which
      greater attention must be paid to rigorous research design, application, and
      analysis. 

PMID- 24025441
TI  - A systematic review on assessment instruments for dementia in persons with
      intellectual disabilities.
AB  - AIM: This work describes an extensive systematic literature review on assessment
      instruments for dementia in persons with intellectual disability (ID). Existing
      instruments for the detection of dementia in persons with ID were collected and
      described systematically. This allows a direct and quick overview of available
      tools. Additionally, it contributes to the availability and usability of
      information about these instruments, thus enhancing further developments in this
      field. METHODS: A systematic literature search in five databases (CINAHL,
      PsycInfo, PubMed, Scopus, and Web of Science) was conducted. In order to include
      gray literature an invisible college approach was used. Relevant studies were
      identified and selected using defined inclusion and exclusion criteria. After the
      selection process all instruments were coded and classified. It was determined
      which concepts they assess, whether they were especially developed or adapted for
      persons with ID, and whether they were designed to assess dementia. The selection
      of relevant papers, as well as the coding of instruments was done independently
      by two researchers. RESULTS: In total, 97 records met the search criteria. Out of
      these, 114 different instruments were extracted. There were 79 instruments to be
      completed by the person with ID, and 35 informant-based instruments.
      Additionally, four test batteries were found. Some of these instruments were
      neither designed for the assessment of dementia, nor for persons with ID.
      CONCLUSIONS: There are a variety of different tools used for the assessment of
      dementia in ID. Nevertheless, an agreed-upon approach or instrument is missing.
      Establishing this would improve the quality of assessment in clinical practice,
      and benefit research. Data collected would become comparable and combinable, and
      allow research to have more informative value.

PMID- 24025443
TI  - Causality and non-equilibrium second-order phase transitions in inhomogeneous
      systems.
AB  - When a second-order phase transition is crossed at a finite rate, the evolution
      of the system stops being adiabatic as a result of the critical slowing down in
      the neighborhood of the critical point. In systems with a topologically
      nontrivial vacuum manifold, disparate local choices of the ground state lead to
      the formation of topological defects. The universality class of the transition
      imprints a signature on the resulting density of topological defects: it obeys a
      power law in the quench rate, with an exponent dictated by a combination of the
      critical exponents of the transition. In inhomogeneous systems the situation is
      more complicated, as the spontaneous symmetry breaking competes with bias caused
      by the influence of the nearby regions that already chose the new vacuum. As a
      result, the choice of the broken symmetry vacuum may be inherited from the
      neighboring regions that have already entered the new phase. This competition
      between the inherited and spontaneous symmetry breaking enhances the role of
      causality, as the defect formation is restricted to a fraction of the system
      where the front velocity surpasses the relevant sound velocity and phase
      transition remains effectively homogeneous. As a consequence, the overall number
      of topological defects can be substantially suppressed. When the fraction of the
      system is small, the resulting total number of defects is still given by a power
      law related to the universality class of the transition, but exhibits a more
      pronounced dependence on the quench rate. This enhanced dependence complicates
      the analysis but may also facilitate experimental testing of defect formation
      theories. 

PMID- 24025442
TI  - Incidence and outcomes of respiratory viral infections in lung transplant
      recipients: a prospective study.
AB  - BACKGROUND: The incidence and outcomes of respiratory viral infections in lung
      transplant recipients (LTR) are not well defined. The objective of this
      prospective study conducted from June 2008 to March 2011 was to characterise the
      incidence and outcomes of viral respiratory infections in LTR. METHODS: Patients
      were seen in three contexts: study-specific screenings covering all seasons;
      routine post-transplantation follow-up; and emergency visits. Nasopharyngeal
      specimens were collected systematically and bronchoalveolar lavage (BAL) was
      performed when clinically indicated. All specimens underwent testing with a wide
      panel of molecular assays targeting respiratory viruses. RESULTS: One hundred and
      twelve LTR had 903 encounters: 570 (63%) were screening visits, 124 (14%) were
      routine post-transplantation follow-up and 209 (23%) were emergency visits.
      Respiratory viruses were identified in 174 encounters, 34 of these via BAL. The
      incidence of infection was 0.83 per patient-year (95% CI 0.45 to 1.52). The viral
      infection rates upon screening, routine and emergency visits were 14%, 15% and
      34%, respectively (p<0.001). Picornavirus was identified most frequently in
      nasopharyngeal (85/140; 60.7%) and BAL specimens (20/34; 59%). Asymptomatic viral
      carriage, mainly of picornaviruses, was found at 10% of screening visits.
      Infections were associated with transient lung function loss and high calcineurin
      inhibitor blood levels. The hospitalisation rate was 50% (95% CI 30% to 70.9%)
      for influenza and parainfluenza and 16.9% (95% CI 11.2% to 23.9%) for other
      viruses. Acute rejection was not associated with viral infection (OR 0.4, 95% CI
      0.1 to 1.3). CONCLUSIONS: There is a high incidence of viral infection in LTR;
      asymptomatic carriage is rare. Viral infections contribute significantly to this
      population's respiratory symptomatology. No temporal association was observed
      between infection and acute rejection.

PMID- 24025444
TI  - Enhanced photovoltaic performance of nanowire dye-sensitized solar cells based on
      coaxial TiO2@TiO heterostructures with a cobalt(II/III) redox electrolyte.
AB  - The growth of a TiO shell at the surface of TiO2 nanowires (NWs) allowed us to
      improve the power conversion efficiency of NW-based dye-sensitized solar cells
      (DSCs) by a factor 2.5. TiO2@TiO core-shell NWs were obtained by a two-step
      process: First, rutile-phase TiO2 NWs were hydrothermally grown. Second, a
      hongquiite-phase TiO shell was electrochemically deposited at the surface of the
      TiO2 NWs. Bare TiO2 and heterojunction TiO2@TiO NW-based DSCs were obtained using
      a cobalt(II/III) redox electrolyte and LEG4 as the dye. With this electrolyte/dye
      combination, DSCs with outstanding Voc values above 900 mV were systematically
      obtained. While TiO2@TiO NW-based DSCs had slightly lower Voc values than bare
      TiO2 NW-based DSCs, they provided 3-fold higher photocurrents, overall reaching
      2.5-fold higher power conversion efficiencies. The higher photocurrents were
      associated with the larger surface roughness and an enhanced charge-carrier
      separation/transfer at the NW/dye interface. 

PMID- 24025445
TI  - Indicators of replicative damage in equine tendon fibroblast monolayers.
AB  - BACKGROUND: Superficial digital flexor tendon (SDFT) injuries of horses usually
      follow cumulative matrix microdamage; it is not known why the reparative
      abilities of tendon fibroblasts are overwhelmed or subverted. Relevant in vitro
      studies of this process require fibroblasts not already responding to stresses
      caused by the cell culture protocols. We investigated indicators of replicative
      damage in SDFT fibroblast monolayers, effects of this on their reparative
      ability, and measures that can be taken to reduce it. RESULTS: We found
      significant evidence of replicative stress, initially observing consistently
      large numbers of binucleate (BN) cells. A more variable but prominent feature was
      the presence of numerous gammaH2AX (gammaH2AX) puncta in nuclei, this being a
      histone protein that is phosphorylated in response to DNA double-stranded breaks
      (DSBs). Enrichment for injury detection and cell cycle arrest factors (p53
      (ser15) and p21) occurred most frequently in BN cells; however, their numbers did
      not correlate with DNA damage levels and it is likely that the two processes have
      different causative mechanisms. Such remarkable levels of injury and binucleation
      are usually associated with irradiation, or treatment with cytoskeletal
      disrupting agents.Both DSBs and BN cells were greatest in subconfluent
      (replicating) monolayers. The DNA-damaged cells co-expressed the replication
      markers TPX2/repp86 and centromere protein F. Once damaged in the early stages of
      culture establishment, fibroblasts continued to express DNA breaks with each
      replicative cycle. However, significant levels of cell death were not measured,
      suggesting that DNA repair was occurring. Comet assays showed that DNA repair was
      delayed in proportion to levels of genotoxic stress. CONCLUSIONS: Researchers
      using tendon fibroblast monolayers should assess their "health" using gammaH2AX
      labelling. Continued use of early passage cultures expressing initially high
      levels of gammaH2AX puncta should be avoided for mechanistic studies and ex-vivo
      therapeutic applications, as this will not be resolved with further replicative
      cycling. Low density cell culture should be avoided as it enriches for both DNA
      damage and mitotic defects (polyploidy). As monolayers differing only slightly in
      baseline DNA damage levels showed markedly variable responses to a further
      injury, studies of effects of various stressors on tendon cells must be very
      carefully controlled.

PMID- 24025446
TI  - Prevalence of genetic risk factors related with thrombophilia and
      hypofibrinolysis in patients with osteonecrosis of the femoral head in Poland.
AB  - BACKGROUND: The etiology of osteonecrosis of femoral head (ONFH) has not been
      fully elucidated. Increased intravascular coagulation and/or hypofibrinolysis
      have been proposed as pathogenic mechanisms. Previous reports demonstrated
      significant association between incidence of ONFH and polymorphisms of genes
      related with thrombophilia especially in Caucasian subjects. The aim of our study
      was to evaluate the relationship between genetic mutations leading to coagulation
      disorders and ONFH in Polish patients. METHODS: We have investigated the
      frequencies of four markers among 68 unrelated individuals with clinically and
      radiographically documented ONFH and among 100 healthy unrelated blood donors in
      Eastern part of Poland. The three genes were involved in thrombophilia: factor V
      Leiden (G1691A), prothrombin (G20210A), Methylenetetrahydrofolate Reductase
      (MTHFR C677T) and one in hypofibrinolysis: Tissue Plasminogen Activator (PLAT
      TPA25 I/D). The samples were genotyped with polymerase chain reaction followed by
      restriction enzyme analysis for the restriction fragment length polymorphisms.
      The allele and genotype frequencies were analyzed in the relation to ONFH
      etiology (idiopathic and secondary), gender, age (patients younger or older than
      50 years) and the number of affected joints (unilateral or bilateral ONFH).
      RESULTS: No significant difference in allele frequencies between patients and
      control groups were observed in genes involved in thrombophilia. We have found a
      statistically significant increased frequency of D allele of PLAT TPA 25 I/D
      polymorphism between the entire group of patients with ONFH and controls
      (p=0,026, OR=1,54, CI 0,99-2,4). D allele frequency was also significantly
      increased in patients with primary ONFH (p=0,009, OR=1,81 CI 1,1-3,01), in males
      (p= 0,013; OR 1,74; 95% CIs 1,08-2,78), patients older than 50 years (p= 0,018,
      OR= 2,04; 95% CIs 1,09-3,82) and in cases with bilateral ONFH (p= 0,01; OR= 1,92;
      95% CIs 1,13-3,27) (Table 9). The differences in DD homozygous genotype frequency
      were statistically significant for patients with idiopathic ONFH compared with
      control group (p=0,023, OR=2,75, CI 0,99-7,9) and in cases of bilateral ONFH
      (p=0,034; OR 3,12; 95% CIs 1,06-9,18) (Table 10). The frequencies of ID
      heterozygous genotype were statistically significantly higher in entire group of
      patients with ONFH (p=0,004 OR 2,71; 95% CIs 1,32-5,57), idiopathic ONFH (p=
      0,01; OR 2,91; 95% CIs 1,24-6,87), males (p=0,0007; OR 3,75; 95% CIs 1,67-8,42),
      patients older than 50 years (p=0,001; OR 6,89; 95% CIs 1,87-25,84) and in cases
      with bilateral ONFH (p=0,009; OR 3,19; 95% CIs 1,26-8,03). CONCLUSION: The
      results suggest that inherited hypofibrinolysis is a risk factor of idiopathic
      ONFH in Polish population.

PMID- 24025447
TI  - Synaptojanin-2 binding protein stabilizes the Notch ligands DLL1 and DLL4 and
      inhibits sprouting angiogenesis.
AB  - RATIONALE: The formation of novel blood vessels is initiated by vascular
      endothelial growth factor. Subsequently, DLL4-Notch signaling controls the
      selection of tip cells, which guide new sprouts, and trailing stalk cells. Notch
      signaling in stalk cells is induced by DLL4 on the tip cells. Moreover, DLL4 and
      DLL1 are expressed in the stalk cell plexus to maintain Notch signaling. Notch
      loss-of-function causes formation of a hyperdense vascular network with disturbed
      blood flow. OBJECTIVE: This study was aimed at identifying novel modifiers of
      Notch signaling that interact with the intracellular domains of DLL1 and DLL4.
      METHODS AND RESULTS: Synaptojanin-2 binding protein (SYNJ2BP, also known as
      ARIP2) interacted with the PDZ binding motif of DLL1 and DLL4, but not with the
      Notch ligand Jagged-1. SYNJ2BP was preferentially expressed in stalk cells,
      enhanced DLL1 and DLL4 protein stability, and promoted Notch signaling in
      endothelial cells. SYNJ2BP induced expression of the Notch target genes HEY1,
      lunatic fringe (LFNG), and ephrin-B2, reduced phosphorylation of ERK1/2, and
      decreased expression of the angiogenic factor vascular endothelial growth factor
      (VEGF)-C. It inhibited the expression of genes enriched in tip cells, such as
      angiopoietin-2, ESM1, and Apelin, and impaired tip cell formation. SYNJ2BP
      inhibited endothelial cell migration, proliferation, and VEGF-induced
      angiogenesis. This could be rescued by blockade of Notch signaling or application
      of angiopoietin-2. SYNJ2BP-silenced human endothelial cells formed a functional
      vascular network in immunocompromised mice with significantly increased vascular
      density. CONCLUSIONS: These data identify SYNJ2BP as a novel inhibitor of tip
      cell formation, executing its functions predominately by promoting Delta-Notch
      signaling.

PMID- 24025449
TI  - Approaches to aspects of optimisation of protection in diagnostic radiology in
      six continents.
AB  - There has been an expansion in the use of x-ray imaging during the last 20 years.
      Effective arrangements for justification of exposures as well as for optimisation
      of protection are crucial. The amount of effort put into the latter, the way in
      which it is organised and the groups carrying this out vary across the globe. A
      simple survey of organisational arrangements relating to performance testing of x
      ray equipment, management of patient dose and other aspects of implementing
      optimisation has been undertaken. A total of 137 completed survey forms were
      received from medical physicists in 48 countries. Results for individual
      countries from which more responses were received, or for groups of neighbouring
      ones, are compared to portray variations. Some performance testing of x-ray
      equipment was mandated in most countries (more than 90%), with the tests being
      performed primarily by hospital or private medical physicists, although other
      groups are involved. Testing of equipment prior to clinical use was generally
      high for most regions, but the frequency was lower in Latin America. There was
      considerable variation in the frequency and regularity of subsequent testing. The
      prevalence of patient dose surveys was high in Europe, but lower in other
      continents. Organisational arrangements for testing performance of x-ray
      equipment, patient dose surveys and implementing optimisation of protection in
      medical exposures across the globe can be divided into five main groups. Hospital
      medical physicists take the lead in western Europe and Australia with the
      involvement of radiographers. Private medical physicists test equipment in
      Brazil, the USA and New Zealand, and have some responsibility for optimisation in
      Brazil. University personnel have significant involvement, together with medical
      physicists in eastern Europe, but the extent of the coverage is uncertain.
      Government personnel and service engineers carry out equipment testing in many
      countries of Africa and Asia, while radiographers have a significant role in
      Thailand and other countries where the number of medical physicists is limited.
      In order for dose surveys to have an impact, action must be taken upon the
      findings, but there must be an effective link between surveyors and radiology
      facility staff to ensure that this is done. 

PMID- 24025448
TI  - Proteolytic processing of Atg32 by the mitochondrial i-AAA protease Yme1
      regulates mitophagy.
AB  - Mitophagy, the autophagic removal of mitochondria, occurs through a highly
      selective mechanism. In the yeast Saccharomyces cerevisiae, the mitochondrial
      outer membrane protein Atg32 confers selectivity for mitochondria sequestration
      as a cargo by the autophagic machinery through its interaction with Atg11, a
      scaffold protein for selective types of autophagy. The activity of mitophagy in
      vivo must be tightly regulated considering that mitochondria are essential
      organelles that produce most of the cellular energy, but also generate reactive
      oxygen species that can be harmful to cell physiology. We found that Atg32 was
      proteolytically processed at its C terminus upon mitophagy induction. Adding an
      epitope tag to the C terminus of Atg32 interfered with its processing and caused
      a mitophagy defect, suggesting the processing is required for efficient
      mitophagy. Furthermore, we determined that the mitochondrial i-AAA protease Yme1
      mediated Atg32 processing and was required for mitophagy. Finally, we found that
      the interaction between Atg32 and Atg11 was significantly weakened in yme1?
      cells. We propose that the processing of Atg32 by Yme1 acts as an important
      regulatory mechanism of cellular mitophagy activity. 

PMID- 24025450
TI  - Preclinical Alzheimer's disease criteria.

PMID- 24025451
TI  - The state of the research for health environment in the ministries of health of
      the Economic Community of the West African States (ECOWAS).
AB  - BACKGROUND: An assessment of the state of the Research for Health (R4H)
      environment can provide relevant information about what aspects of national
      health research systems needs strengthening, so that research output can be
      relevant to meet national priorities for decision-making. There is limited
      information on the state of the R4H environment in the Economic Community of West
      African States (ECOWAS). This article describes the state of the R4H environment
      within the Ministries of Health of the ECOWAS member states and outlines of some
      possibilities to strengthen health research activities within the ECOWAS region.
      METHODS: Information on the national-level R4H environment (governance and
      management; existence of a national policy; strategic and research priorities
      documents; ethics committees; research funds; coordination structures; monitoring
      and evaluation systems; networking and capacity building opportunities) was
      collected from the Ministries of Health research units in 14 ECOWAS countries
      using self-administered questionnaires. A workshop was held where country report
      presentations and group discussions were used to review and validate responses.
      Data from the discussions was transcribed using Nvivo, and strengths, weaknesses,
      opportunities and threats (SWOT) analysis of the functioning of the units was
      done using Robert Preziosi's organisational diagnosis tool. RESULTS: The findings
      indicate that as of January 2011, 50% of ECOWAS countries had established
      directorates for health research with defined terms of reference. The existing
      funding mechanisms were inadequate to support the research structures within and
      outside the MoHs, and for building the capacity of researchers. Networking and
      monitoring activities were weak and only 7% of the directors of research units
      were trained in research management. The majority (85.7%) of countries had
      broader national health policies, and 57% of the countries had some form of
      policy or strategic document for research development. Half of the countries had
      developed national research priorities. CONCLUSIONS: These results call for
      urgent action to improve the research environment in the Ministries of Health in
      the West African sub-region.

PMID- 24025452
TI  - Analytical accuracy and user-friendliness of the Afinion point-of-care CRP test.

PMID- 24025453
TI  - Blastic plasmacytoid dendritic cell neoplasm with EWSR1 gene rearrangement.

PMID- 24025455
TI  - Diterpenylquinone hybrids: synthesis and assessment of gastroprotective
      mechanisms of action in human cells.
AB  - A modern approach in the search for new bioactive molecules is the synthesis of
      novel chemical entities combining molecules of different biosynthetic origin
      presenting biological effects as single compounds. Gastroprotective compounds
      from South American medicinal plants, namely quinones and diterpenes, were used
      as building blocks to obtain hybrid diterpenylquinones. Starting from the labdane
      diterpene junicedric acid and two isomers, as well as from three quinones,
      including lapachol, 18 hybrid molecules were synthesized. Six of them are
      described for the first time. The potential gastroprotective mechanisms of action
      of the compounds were assessed in dose-response experiments using human gastric
      epithelial cells (AGS) and human lung fibroblasts (MRC-5). The following studies
      were carried out: stimulation of cell proliferation, cytoprotection against
      sodium taurocholate (NaT)-induced damage, synthesis of PGE2 and total reduced
      sulfhydryl (GSH) content. The antioxidant capacity of the compounds was
      determined on the inhibition of the lipoperoxidation in human erythrocyte
      membranes. Hybrid compounds presented activities different from those shown by
      the starting compounds, supporting the potential of this approach in the search
      for new bioactive molecules. The effects might be modulated by selective
      modification in the terpene or quinone moieties of the new molecules. Structure
      activity relationships are discussed. 

PMID- 24025454
TI  - Hereditary breast cancer: ever more pieces to the polygenic puzzle.
AB  - Several susceptibility genes differentially impact on the lifetime risk for
      breast cancer. Technological advances over the past years have enabled the
      detection of genetic risk factors through high-throughput screening of large
      breast cancer case-control series. High- to intermediate penetrance alleles have
      now been identified in more than 20 genes involved in DNA damage signalling and
      repair, and more than 70 low-penetrance loci have been discovered through recent
      genome-wide association studies. In addition to classical germ-line mutation and
      single-nucleotide polymorphism, copy number variation and somatic mosaicism have
      been proposed as potential predisposing mechanisms. Many of the identified loci
      also appear to influence breast tumour characteristics such as estrogen receptor
      status. In this review, we briefly summarize present knowledge about breast
      cancer susceptibility genes and discuss their implications for risk prediction
      and clinical practice. 

PMID- 24025456
TI  - Sex differences in the hepatic cholesterol sensing mechanisms in mice.
AB  - Cholesterol is linked to many multifactorial disorders, including different forms
      of liver disease where development and severity depend on the sex. We performed a
      detailed analysis of cholesterol and bile acid synthesis pathways at the level of
      genes and metabolites combined with the expression studies of hepatic cholesterol
      uptake and transport in female and male mice fed with a high-fat diet with or
      without cholesterol. Lack of dietary cholesterol led to a stronger response of
      the sterol sensing mechanism in females, resulting in higher expression of
      cholesterogenic genes compared to males. With cholesterol in the diet, the genes
      were down-regulated in both sexes; however, males maintained a more efficient
      hepatic metabolic flux through the pathway. Females had higher content of hepatic
      cholesterol but this was likely not due to diminished excretion but rather due to
      increased synthesis and absorption. Dietary cholesterol and sex were not
      important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1
      upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or
      Abcg8 transporters. On the other hand, females had higher expression of the Ldlr
      and Cd36 genes. These findings explain sexual dimorphism of cholesterol
      metabolism in response to dietary cholesterol in a high-fat diet in mice, which
      contributes to understanding the sex-basis of cholesterol-associated liver
      diseases. 

PMID- 24025457
TI  - First chemical constituents from Cordia exaltata Lam and antimicrobial activity
      of two neolignans.
AB  - The phytochemical study of Cordia exaltata Lam. (Boraginaceae) led to the
      isolation, through chromatographic techniques, of nineteen secondary metabolites:
      8,8'dimethyl-3,4,3',4'-dimethylenedioxy-7-oxo-2,7'cyclolignan (1), 8,8'-dimethyl
      4,5-dimethoxy-3',4'-methylenodioxy-7-oxo-2,7'cyclolignan (2), sitosterol (3a),
      stigmasterol (3b), sitosterol-3-O-beta-D-glucopyranoside (4a), stigmasterol-3-O
      beta-D-glucopyranoside (4b), phaeophytin A (5), 132-hydroxyphaeophytin A (6), 173
      ethoxypheophorbide A (7), 132-hydroxy-173-ethoxypheophorbide A (8), m-methoxy-p
      hydroxybenzaldehyde (9), (E)-7-(3,4-dihydroxyphenyl)-7-propenoic acid (10), 1
      benzopyran-2-one (11), 7-hydroxy-1-benzopyran-2-one (12), 2,5-bis-(3',4'
      methylenedioxiphenyl)-3,4-dimethyltetrahydrofuran (13), 3,4,5,3',5'-pentamethoxy
      1'-allyl-8.O.4'-neolignan (14), 3,5,7,3',4'-pentahydroxyflavonol (15), 5,7
      dihydroxy-4'-methoxyflavone (16), 5,8-dihydroxy-7,4'-dimethoxyflavone (17),
      kaempherol 3-O-beta-D-glucosyl-6''-alpha-L-ramnopyranoside (18) and kaempherol
      3,7-di-O-alpha-L-ramnopyranoside (19). Their structures were identified by 1H and
      13C-NMR using one and two-dimensional techniques. In addition, the antimicrobial
      activity of compounds 1, 2, 13 and 14 against bacteria and fungi are reported
      here for the first time.

PMID- 24025458
TI  - Iodine-catalyzed prins cyclization of homoallylic alcohols and aldehydes.
AB  - The iodine-catalyzed Prins cyclization of homoallylic alcohols and aldehydes was
      investigated under metal-free conditions and without additives. Anhydrous
      conditions and inert atmosphere are not required. The reaction of 2-(3,4
      dihydronaphthalen-1-yl)propan-1-ol and 21 aldehydes (aliphatic and aromatic) in
      CH2Cl2 in the presence of 5 mol % of iodine gave 1,4,5,6-tetrahydro-2H
      benzo[f]isochromenes in 54%-86% yield. Under similar conditions, the Prins
      cyclization of six alcohols containing an endocyclic double bond (primary,
      secondary, or tertiary) led to dihydropyrans in 52%-91% yield. The acyclic
      homoallylic alcohols gave 4-iodo-tetrahydropyran in 29%-41% yield in the presence
      of 50 mol % of iodine. This type of substrate is the main limitation of the
      methodology. The relative configuration of the products was assigned by NMR and X
      ray analysis. The mechanism and the ratio of the products are discussed, based on
      DFT calculations.

PMID- 24025459
TI  - Cloning and characterization of a 2-Cys peroxiredoxin from Babesia gibsoni.
AB  - Peroxiredoxins (Prxs) are a family of antioxidant enzymes. Here, we cloned a 2
      Cys Prx, BgTPx-1, from the canine Babesia parasite B. gibsoni. Sequence identity
      between BgTPx-1 and 2-Cys Prx of B. bovis was 81% at the amino acid level. Enzyme
      activity assay by using recombinant BgTPx-1 (rBgTPx-1) indicated that BgTPx-1 has
      antioxidant activity. Antiserum from a mouse immunized with rBgTPx-1 reacted with
      parasite lysates and detect a protein with a monomeric size of 22 kDa and also a
      44 kDa protein, which might be an inefficiently reduced dimer. BgTPx-1 was
      expressed in the cytoplasm of B. gibsoni merozoites. These results suggest that
      the BgTPx-1 may play a role to control redox balance in the cytoplasm of B.
      gibsoni. 

PMID- 24025461
TI  - Modelling of a novel high-impedance matching layer for high frequency (>30 MHz)
      ultrasonic transducers.
AB  - This work describes a new approach to impedance matching for ultrasonic
      transducers. A single matching layer with high acoustic impedance of 16 MRayls is
      demonstrated to show a bandwidth of around 70%, compared with conventional single
      matching layer designs of around 50%. Although as a consequence of this
      improvement in bandwidth, there is a loss in sensitivity, this is found to be
      similar to an equivalent double matching layer design. Designs are calculated by
      using the KLM model and are then verified by FEA simulation, with very good
      agreement Considering the fabrication difficulties encountered in creating a high
      frequency double matched design due to the requirement for materials with
      specific acoustic impedances, the need to accurately control the thickness of
      layers, and the relatively narrow bandwidths available for conventional single
      matched designs, the new approach shows advantages in that alternative (and
      perhaps more practical) materials become available, and offers a bandwidth close
      to that of a double layer design with the simplicity of a single layer design.
      The disadvantage is a trade-off in sensitivity. A typical example of a
      piezoceramic transducer matched to water can give a 70% fractional bandwidth
      (comparable to an ideal double matched design of 72%) with a 3dB penalty in
      insertion loss.

PMID- 24025460
TI  - 4-thiouridine inhibits rRNA synthesis and causes a nucleolar stress response.
AB  - High concentrations (> 100 uM) of the ribonucleoside analog 4-thiouridine (4sU)
      is widely used in methods for RNA analysis like photoactivatable-ribonucleoside
      enhanced crosslinking and immunoprecipitation (PAR-CLIP) and nascent messenger
      (m)RNA labeling (4sU-tagging). Here, we show that 4sU-tagging at low
      concentrations <= 10 uM can be used to measure production and processing of
      ribosomal (r)RNA. However, elevated concentrations of 4sU (> 50 uM), which are
      usually used for mRNA labeling experiments, inhibit production and processing of
      47S rRNA. The inhibition of rRNA synthesis is accompanied by nucleoplasmic
      translocation of nucleolar nucleophosmin (NPM1), induction of the tumor
      suppressor p53, and inhibition of proliferation. We conclude that metabolic
      labeling of RNA by 4sU triggers a nucleolar stress response, which might
      influence the interpretation of results. Therefore, functional ribosome
      biogenesis, nucleolar integrity, and cell cycle should be addressed in 4sU
      labeling experiments. 

PMID- 24025462
TI  - In praise of coffee ... and caffeine.

PMID- 24025463
TI  - Nursing swallow screens: why is testing water only not enough?
AB  - The speech-language pathologist (SLP) standardized a Nursing Bedside Swallowing
      Screen (NBSS) tool for all patients admitted to the hospital. The adults engaged
      in the NBSS before oral intake (i.e., medication included) as part of the Brain
      Attack Pathway for patients with neurological symptoms. If the patient failed the
      NBSS in the emergency department (ED), then the screen was repeated again after
      the patient had been admitted before the SLP dysphagia evaluation. Fifty-three
      male and female patients ranging from 34 to 96 years old with an initial
      diagnosis of stroke or transient ischemic attack (TIA) admitted during an 8-week
      time period from April 25, 2010, to June 19, 2010, were included in this study.
      There were 32 women and 17 men including 27 strokes and 22 TIAs tested. As a
      whole, the NBSS and SLP dysphagia evaluation results were consistent with each
      other for 40 of 46 patients (86.96% perfect agreement). The NBSS had 74% of
      sensitivity (34 of 46) with the nursing and the speech pathologist in agreement
      with the patients passing the swallow screen. Accurate identification of
      aspiration with the patients failing the NBSS was evident with the nursing and
      speech pathology assessment, which resulted in 83% of sensitivity (10 of 12). The
      positive predictive value with the corresponding identification of aspiration
      with the staff was 96% (44 of 46). The naturalistic observation of the patients
      exhibited internal consistency reliability between the two disciplines.
      Extraneous variables affecting the results included spontaneous resolution of
      stroke or TIA symptoms or the patient's decline in neurological status. VIDEO
      ABSTRACT: For more insights from the authors, see Supplemental Digital Content 1,
      at http://links.lww.com/JNN/A9.

PMID- 24025465
TI  - Surveillance as an intervention in the care of stroke patients.
AB  - BACKGROUND: The term surveillance describes nurses' cognitive work to identify
      and prevent patient complications. Surveillance involves frequent assessment of
      patients, attention to cues, and recognition of complications. Surveillance
      serves to prevent the phenomenon "failure to rescue," which is defined as the
      inability to recognize a complication that results in the loss of a patient's
      life. Previous research has focused on differences between novices and experts
      during simulated tasks such as developing a plan of care. More recently,
      attention has focused on the early recognition of patient complications. Little
      research has been conducted on surveillance, especially with respect to the
      intervention during the delivery of care. PURPOSE: The purpose of this study was
      to explore the nursing intervention of surveillance in the care of stroke
      patients. METHODS AND DESIGN: A descriptive exploratory design using think-aloud
      was employed. The study focused on 10 nurses working on a medical neurology unit
      and their patients in a large Midwestern academic health center. While providing
      care to a stroke patient, the nurse was prompted to think aloud as they (1)
      received report, (2) performed an initial assessment of the patient, and (3)
      concluded the work shift. Data analysis was conducted using content analysis to
      define the cues and information processing strategies used by these nurses during
      the delivery of care to stroke patients. FINDINGS AND CONCLUSION: The findings
      suggest that nurses in this study used surveillance. Using cues from change-of
      shift handoff information, a mental image of what the patient would look/be like
      was formed. This mental image served as a baseline for the evaluation of the
      patient's current state.

PMID- 24025464
TI  - Usage and design evaluation by family caregivers of a stroke intervention web
      site.
AB  - BACKGROUND: Four of five families are affected by stroke. Many caregivers access
      the Internet and gather healthcare information from Web-based sources. DESIGN:
      The purpose of this descriptive evaluation was to assess the usage and design of
      the Caring~Web site, which provides education/support for family caregivers of
      persons with stroke residing in home settings. SAMPLE AND SETTING: Thirty-six
      caregivers from two Midwest states accessed this intervention in a 1-year study.
      The average participant was 54 years old, White, woman, and the spouse of the
      care recipient. METHODS: In a telephone interview, four Web site questions were
      asked twice a month/bimonthly, and a 33-item survey at the conclusion of the
      study evaluated the Web site usage and design of its components. Descriptive
      analysis methods were used, and statistics were collected on the number of visits
      to the Web site. RESULTS: On average, participants logged on to the Web site 1-2
      hours per week, although usage declined after several months for some
      participants. Participants positively rated the Web site's appearance and
      usability that included finding the training to be adequate. CONCLUSION: Web site
      designers can replicate this intervention for other health conditions.

PMID- 24025466
TI  - A study to explore nurses' knowledge in using the Glasgow Coma Scale in an acute
      care hospital.
AB  - BACKGROUND: The Glasgow Coma Scale (GCS) is a neurological instrument, which
      measures the "depth and duration of impaired consciousness." The appeal of the
      GCS lies in its applicability in a wide variety of clinical situations as well as
      its ease of use by a range of healthcare staff. However, the GCS is not without
      its weaknesses and limitations. Its ease of use opens it up to misinterpretation
      and misapplication. Despite the propensity for incorrect assessment, the GCS
      remains in use in the clinical setting and enjoys an "unwarranted and privileged
      position." This creates an issue to patient care as the GCS is an important
      instrument in communicating an accurate assessment of the patient's condition
      between clinical staff. OBJECTIVES: The aim of this study was to investigate
      nurses' knowledge in using the GCS and the demographic factors influencing
      knowledge of the GCS. METHODOLOGY: This is a correlational observational study
      conducted in one acute care hospital in Singapore. The participants were
      registered nurses involving in bedside nursing care. A self-administered
      questionnaire was provided to the participants via ward managers. The
      quantitative responses were collated and analyzed using SPSS 16.0. RESULTS: Type
      of clinical discipline (i.e., neuroscience, general medicine, and neurointensive
      care unit; beta = 0.51, p < .001) and the length of experience in a neuroscience
      setting (beta = 0.22, p = .005) were significant in determining a nurses'
      knowledge of the GCS. Nurses in the neonatal intensive care unit scored the
      highest mean scores (12.7), whereas nurses from the general medicine wards scored
      the lowest mean scores (9.7). Nurses who worked in a neuroscience setting for 6
      years or more scored higher mean scores (11.9) on the knowledge scale, whereas
      nurses who worked in a neuroscience setting for less than a year scored lower
      mean scores (10.0). CONCLUSION: Educational interventions and guidelines in
      performing GCS assessment are suggested to maintain and improve knowledge in
      performing the GCS.

PMID- 24025467
TI  - Using evidence to improve satisfaction with medication side-effects education on
      a neuro-medical surgical unit.
AB  - Patient satisfaction is viewed as a significant indicator of quality of care.
      More specifically, improving patient satisfaction related to communication about
      medications and potential side effects can improve healthcare outcomes. Patient
      satisfaction scores related to medication side effects on a neuro-medical
      surgical unit were monitored following a quality improvement program. These
      patients frequently experience cognitive impairment and functional difficulties
      that can affect the way they understand and handle medications. The purpose of
      this quality improvement practice change was to (a) develop an educational
      approach for post acute neurosurgical patients and (b) evaluate whether the use
      of the approach is successful in improving patient satisfaction scores related to
      medication education on side effects. The quality improvement program
      interventions included (a) patient informational handouts inserted into admission
      folders, (b) nurse education about the importance of providing education on side
      effects to patient and discussion of their involvement with the program, (c) unit
      flyers with nurse education, and (d) various communications with bedside nurses
      through personal work mail and emails. The primary focus was for nurses to employ
      the "teach back" method to review and reinforce the medication side-effect
      teaching with patients. Evaluation of the data showed an increase in patient
      satisfaction after the implementation of the "Always Ask" program. 

PMID- 24025468
TI  - Bedside coaching to improve nurses' recognition of delirium.
AB  - Delirium is a widespread complication of hospitalization and is frequently
      unrecognized by nurses and other healthcare professionals. Patients with
      neuroscience diagnoses are at increased risk for delirium as compared with other
      patients. The aims of this quality improvement project were to (1) increase
      neuroscience nurses' knowledge of delirium, (2) integrate coaching into evidence
      based practice, and (3) evaluate the effectiveness of this combined approach to
      improve nurses' recognition of delirium on a neuroscience unit. Institutional
      review board approval was obtained. A retrospective chart review of randomly
      selected patients admitted before the intervention was completed. The (modified)
      Nurse's Knowledge of Delirium Tool was electronically administered to nursing
      staff (n = 47), followed within 2 weeks by a didactic presentation on delirium.
      Bedside coaching was performed over a period of 4 weeks. The (modified) Nurses
      Knowledge of Delirium Tool was electronically readministered to nurses 4 weeks
      later to determine the change in aggregate knowledge. A postintervention chart
      review was conducted. SPSS software was used to analyze descriptive statistics
      with regard to chart reviews, documentation, and change in questionnaire scores.
      Findings reveal that neuroscience nurses recognize the absence of delirium 94.4%
      of the time and the presence of delirium 100% of the time after a didactic
      session and coaching. The postintervention chart review showed a statistically
      significant increase (p = .000) in the documentation of delirium screening
      results. Expert coaching at the bedside may be a reliable method for teaching
      nurses to use evidence-based screening tools to detect delirium in patients with
      neuroscience diagnoses. 

PMID- 24025469
TI  - Validation of the Hester Davis Scale for fall risk assessment in a neurosciences
      population.
AB  - BACKGROUND AND PURPOSE: Fall risk assessment is a necessary component of fall
      prevention programs. Accurate instruments to predict the risk of falling are
      paramount in identifying the correct patients in need of fall prevention
      measures. The purpose of this study was to prospectively validate the Hester
      Davis Scale (HDS) for fall risk assessment in an acute care setting in the South
      Central United States. METHODS: The HDS was prospectively validated in 1,904
      patients on a neurosciences unit. RESULTS: Using an initial cut score of 7
      produced a sensitivity of 100% and specificity of 24.9%. Receiver Operating
      Characteristic Analysis evidenced a cut score of 10 that would produce a more
      desirable sensitivity and specificity of 90.9% and 47.1%, respectively.
      CONCLUSION: The results of the psychometric evaluation and validation of the HDS
      support its use in clinical practice.

PMID- 24025471
TI  - Clinical practice guideline series update.
AB  - Approximately 20 per 100,000 people in the United States are currently living
      with myasthenia gravis (MG). MG is a chronic condition that occurs in all
      genders, ethnicities, and ages. The result of a defect at the neuromuscular
      junction, MG is characterized by fluctuating muscle weakness and fatigue. The
      purpose of the first edition of this American Association of Neuroscience Nurses'
      Clinical Practice Guideline is to summarize what is currently known about MG and
      to provide the reader with nursing-specific recommendations based on supporting
      evidence from nursing and other disciplines. Nursing Management of the Patient
      with Myasthenia Gravis includes information on epidemiology; types and
      classification of MG; pathophysiology; clinical features; clinical course;
      diagnostic tests; assessment; pharmacological, immunological, and surgical
      management; and the nurses' pivotal role in the care of the patient with MG. 

PMID- 24025473
TI  - Knowledge of stroke and cerebrovascular risk factors among Jordanian adults.
AB  - This study aimed to identify the level of knowledge of stroke and cerebrovascular
      risk factors among Jordanian adults. It also aimed to measure the prevalence of
      cerebrovascular risk factors and to compare the stroke-related knowledge among
      participants based on their sociodemographical data. Two hundred twenty-four
      participants were included in this cross-sectional descriptive study. Data on
      prevalence and knowledge of stroke and cerebrovascular risk factors were
      collected through self-report questionnaires. Widespread prevalence of
      cerebrovascular risk factors was noted. The most common risk factors were
      inactivity (74%), overweight and obesity (59%), and smoking (34%). Moreover, only
      30% of the study participants were able to enumerate three or more risk factors.
      The most commonly recognized risk factors were smoking (76%), hyperlipidemia
      (60%), and obesity (53%). Participants lacked basic knowledge about stroke; the
      average score for stroke knowledge was 8.8 of 20, with 49% of the participants
      achieving lower than the average score. Therefore, community awareness of stroke
      and cerebrovascular risk factors should be increased through national health
      education campaigns. In addition, health promotion programs should be adopted.
      They need to focus on utilizing available resources to reduce the high prevalence
      of major cerebrovascular risk factors in the Jordanian community. This will in
      turn reduce people's risk of experiencing strokes and other cerebrovascular
      diseases. 

PMID- 24025470
TI  - The role of neuroplasticity and cognitive reserve in aging with HIV:
      recommendations for cognitive protection and rehabilitation.
AB  - By and large, the immune systems of people infected with HIV are being protected
      and maintained by advances in highly active antiretroviral therapy; as such, this
      is extending the lives of people into old age. Unfortunately, for many living
      with this disease, HIV is associated with neuroinflammation, co-morbidities, and
      accelerated aging which can compromise brain function, resulting in cognitive
      deficits. The purpose of this article is to highlight how to interpret these
      deficits within the framework of neuroplasticity and cognitive reserve for this
      clinical population. We suggest several recommendations for cognitive
      rehabilitation and mitigation such as addressing lifestyle factors,
      psychostimulants, cognitive remediation therapy, and treatment of depression and
      anxiety. Implications for nursing research and practice are posited. 

PMID- 24025474
TI  - Establishing the position of neurosurgery nurse coordinator as a catalyst for
      advancing quality of care in a tertiary hospital in Israel.
AB  - BACKGROUND: The role of neurosurgery nurse coordinator is unique in Israel and
      was developed to provide a comprehensive response to the needs of patients
      undergoing cranial surgery to remove various types of tumors. The creation of the
      neurosurgery nurse coordinator role was based on patient and staff needs
      assessment and focused on two major areas: (1) the patient and his or her family
      creating personal and empathic communication with the goal of offering emotional
      support, providing support to assist in relieving symptoms, coordinating between
      the patient and/or the patient's family and the physicians and consultants, and
      assisting with bureaucratic processes and with familiarization with the
      hospital's medical environment; and (2) establishing departmental processes
      related to improving patient care within a multidisciplinary team. OBJECTIVE: The
      aim of this study was to investigate the needs and level of satisfaction of
      patients and their families, hospitalized in the neurosurgery department for the
      surgical removal of cranial tumors. METHODS: Satisfaction survey is composed of
      47 questions. SAMPLE: A convenience sample of 67 patients completed a
      satisfaction survey related to various aspects of their hospitalization.
      FINDINGS: The study results reflect patient needs for emotional support,
      information, and additional education. These findings emphasize the great
      importance of the position of nurse coordinator in the neurosurgery department.

PMID- 24025475
TI  - Bodily ownership and self-location: components of bodily self-consciousness.
AB  - Recent research on bodily self-consciousness has assumed that it consists of
      three distinct components: the experience of owning a body (body ownership); the
      experience of being a body with a given location within the environment (self
      location); and the experience of taking a first-person, body-centered,
      perspective on that environment (perspective). Here we review recent neuroimaging
      studies suggesting that at least two of these components-body ownership and self
      location-are implemented in rather distinct neural substrates, located,
      respectively, in the premotor cortex and in the temporo-parietal junction. We
      examine these results and consider them in relation to clinical evidence from
      patients with altered body perception and work on a variety of multisensory, body
      related illusions, such as the rubber hand illusion, the full body illusion, the
      body swap illusion and the enfacement illusion. We conclude by providing a
      preliminary synthesis of the data on bodily self-consciousness and its neural
      correlates. 

PMID- 24025476
TI  - P-type Cu(2)O/SnO bilayer thin film transistors processed at low temperatures.
AB  - P-type Cu2O/SnO bilayer thin film transistors (TFTs) with tunable performance
      were fabricated using room temperature sputtered copper and tin oxides. Using
      Cu2O film as capping layer on top of a SnO film to control its stoichiometry, we
      have optimized the performance of the resulting bilayer transistor. A transistor
      with 10 nm/15 nm Cu2O to SnO thickness ratio (25 nm total thickness) showed the
      best performance using a maximum process temperature of 170  degrees C. The
      bilayer transistor exhibited p-type behavior with field-effect mobility, on-to
      off current ratio, and threshold voltage of 0.66 cm(2) V(-1) s(-1), 1.5*10(2),
      and -5.2 V, respectively. The advantages of the bilayer structure relative to
      single layer transistor are discussed. 

PMID- 24025477
TI  - Inherited catalase deficiency: is it benign or a factor in various age related
      disorders?
AB  - Hydrogen peroxide was - and is still - considered toxic for a wide range of
      living organisms. Oxidative stress occurs when there is an excess of pro-oxidants
      over antioxidants and it has been implicated in several diseases. Catalase is
      involved in hydrogen peroxide catabolism and is important in defense against
      oxidative stress. Acatalasemia means the inherited near-total deficiency of
      catalase activity, usually in reference to red cell catalase. Acatalasemia was
      thought at first to be an asymptotic disorder. In the absence of catalase,
      neither the Japanese, or Hungarian acatalasemics nor acatalasemic mice had
      significantly increased blood glutathione peroxidase activity. In animal models,
      catalase deficient tissues show much slower rates of removal of extracellular
      hydrogen peroxide. In catalase knock-out mice, a decreased hydrogen peroxide
      removing capacity and increased reactive oxygen species formation were reported.
      Hydrogen peroxide may cause methemoglobinemia in patients with catalase
      deficiency. During anesthesia for a Japanese acatalasemic patient the
      disinfection with hydrogen peroxide solution caused severe methemoglobinemia.
      Patients with inherited catalase deficiency, who are treated with uric acid
      oxidase (rasburicase) may experience very high concentrations of hydrogen
      peroxide and may suffer from methemoglobinemia and hemolysis. The high (18.5%)
      prevalence of diabetes mellitus in inherited catalase deficient individuals and
      the earlier (10 years) manifestation of the disease may be attributed to the
      oxidative damage of oxidant sensitive, insulin producing pancreatic beta-cells.
      Ninety-seven of 114 acatalasemics had diseases related to oxidative stress and
      aging. The oxidative stress due to catalase deficiency could contribute to the
      manifestation of diabetes while for the other diseases it may be one of the
      factors in their causations. In summary, inherited catalase deficiency is
      associated with clinical features, pathologic laboratory test results, age and
      oxidative stress related disorders. Rather than considering it a benign
      condition, it should be considered as a complicating condition for aging and
      oxidative stress. 

PMID- 24025478
TI  - Development of an integrative cessation program for co-smokers of cigarettes and
      cannabis: demand analysis, program description, and acceptability.
AB  - BACKGROUND: Tobacco and cannabis use are strongly interrelated, but current
      national and international cessation programs typically focus on one substance,
      and address the other substance either only marginally or not at all. This study
      aimed to identify the demand for, and describe the development and content of,
      the first integrative group cessation program for co-smokers of cigarettes and
      cannabis. METHODS: First, a preliminary study using expert interviews, user focus
      groups with (ex-)smokers, and an online survey was conducted to investigate the
      demand for, and potential content of, an integrative smoking cessation program
      (ISCP) for tobacco and cannabis co-smokers. This study revealed that both experts
      and co-smokers considered an ISCP to be useful but expected only modest levels of
      readiness for participation.Based on the findings of the preliminary study, an
      interdisciplinary expert team developed a course concept and a recruitment
      strategy. The developed group cessation program is based on current treatment
      techniques (such as motivational interviewing, cognitive behavioural therapy, and
      self-control training) and structured into six course sessions.The program was
      evaluated regarding its acceptability among participants and course instructors.
      RESULTS: Both the participants and course instructors evaluated the course
      positively. Participants and instructors especially appreciated the group
      discussions and the modules that were aimed at developing personal strategies
      that could be applied during simultaneous cessation of tobacco and cannabis, such
      as dealing with craving, withdrawal, and high-risk situations. CONCLUSIONS: There
      is a clear demand for a double cessation program for co-users of cigarettes and
      cannabis, and the first group cessation program tailored for these users has been
      developed and evaluated for acceptability. In the near future, the feasibility of
      the program will be evaluated. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN15248397.

PMID- 24025479
TI  - A survey describing the use of complementary therapies and medicines by women
      attending a family planning clinic.
AB  - BACKGROUND: Complementary medicines (CMs) are widely used by women. Although,
      women in Australia are frequent users of CM, few studies have examined their
      utilisation by women attending a family planning service. The aim of this study
      was to examine (i) the extent of and type of CM, (ii) women's views about safety
      and efficacy, and (iii) the factors influencing women's decision-making. METHODS:
      A cross-sectional survey using a convenience sample of 221 women aged greater
      than 18 years attending a family planning (FP) service was undertaken over a two
      week period in Sydney, Australia. An anonymous self-administered questionnaire
      was designed to examine women's current and previous use of CMs, their attitudes
      towards safety and effectiveness, the factors influencing their decision-making,
      and their disclosure of CM use to a FP health professional. Demographic questions
      were designed to describe the diversity of the participants. Logistic regression
      was used to examine the association between CM use and demographics. RESULTS:
      Sixty-seven percent of women surveyed were currently using CMs, and 83% reported
      use during the previous 12 months. Most respondents utilised CMs to maintain
      their general health or for prevention of ill health. Over 30% of women lacked
      information to make an informed response to questions examining their views about
      the safety of CMs. Forty-four percent of participants stated they discussed their
      use of CMs with their FP providers. The main reason why women did not mention CMs
      was they did not see the relevance to their consultation (43%). Lower rates of CM
      use were found for younger women (OR 0.24, 95% CI 0.09-0.61), and those not
      completing high school (OR 0.44, 95% 0.20-1.00). CONCLUSION: The use of CM is
      very common among women attending an Australian FP clinic, however our findings
      may not be generalisable to all women. We identified a notable gap in women's
      awareness of the potential for interactions between CM and prescribed medication.
      Our findings also emphasise the need for healthcare providers to initiate
      discussions with clients about their utilisation of CM.

PMID- 24025481
TI  - The role of causality in tunable Fermi gas condensates.
AB  - We develop a new formalism for the description of the condensates of cold Fermi
      atoms whose speed of sound can be tuned with the aid of a narrow Feshbach
      resonance. We use this to look for spontaneous phonon creation that mimics
      spontaneous particle creation in curved space-time in Friedmann-Robertson-Walker
      and other model universes. 

PMID- 24025480
TI  - The avian and mammalian host range of highly pathogenic avian H5N1 influenza.
AB  - Highly pathogenic H5N1 influenza viruses have been isolated from a number of
      avian and mammalian species. Despite intensive control measures the number of
      human and animal cases continues to increase. A more complete understanding of
      susceptible species and of contributing environmental and molecular factors is
      crucial if we are to slow the rate of new cases. H5N1 is currently endemic in
      domestic poultry in only a handful of countries with sporadic and unpredictable
      spread to other countries. Close contact of terrestrial bird or mammalian species
      with infected poultry/waterfowl or their biological products is the major route
      for interspecies transmission. Intra-species transmission of H5N1 in mammals,
      including humans, has taken place on a limited scale though it remains to be seen
      if this will change; recent laboratory studies suggest that it is indeed
      possible. Here we review the avian and mammalian species that are naturally
      susceptible to H5N1 infection and the molecular factors associated with its
      expanded host range. 

PMID- 24025482
TI  - Comparison of different phantom designs for CT scanner automatic tube current
      modulation system tests.
AB  - Modern CT scanners modulate tube current during scans according to patient size,
      shape and attenuation. However, the ATCM (automatic tube current modulation)
      systems for different CT manufacturers work on different principles. Although the
      systems are used for the majority of patients and examinations, there is no
      standard phantom for routine quality control of CT scanner ATCM operation. The
      ideal phantom for testing these systems should be capable of evaluating how tube
      current and image quality as well as dose vary according to changes in patient
      size and shape. For this study, a conical phantom designed by ImPACT has been
      compared with two phantoms made from elliptical sections with varying dimensions.
      The concept of the designs is to reflect the ATCM performance for the varying
      shapes and dimensions along the length of the human body. The first phantom
      comprises five elliptical sections with a wide range of different dimensions and
      the second has three sections that are more similar in size. The phantoms have
      been used to test ATCM systems for Philips, Siemens, GE and Toshiba scanners.
      Although the results of the tube current modulation patterns were similar for all
      CT scanners, the abrupt changes in attenuation for the first sectional phantom
      provoked an abnormal ATCM response for the GE and Toshiba scanners. The second
      sectional phantom was developed from the results of the first, and was more
      effective for ATCM system testing and could be used for dose and image quality
      assessment in standard positions. However, the ImPACT conical phantom provided
      the best overall assessment of performance in terms of tube current modulations
      and noise pattern. 

PMID- 24025483
TI  - Assessing the causes and consequences of co-polymerization in amyloid formation.
AB  - How, and why, different proteins form amyloid fibrils is most often studied in
      vitro using a single purified protein sequence. However, many amyloid diseases
      involve co-aggregation of different protein species, including proteins
      with/without post-translational modifications (e.g., different strains of PrP),
      proteins of different length (e.g., beta2-microglobulin and DeltaN6, Abeta40, and
      Abeta42), sequence variants (e.g., Abeta and Abeta(ARC)), and proteins from
      different organisms (e.g., bovine PrP and human PrP). The consequences of co
      aggregation of different proteins upon the structure, stability, species
      transmission and toxicity of the resulting amyloid aggregates is discussed here,
      including the role of co-aggregation in expanding the repertoire of oligomeric
      and fibrillar structures and how this can affect their biological and biophysical
      properties.

PMID- 24025486
TI  - Standardization of T1 measurements with MOLLI in differentiation between health
      and disease--the ConSept study.
AB  - BACKGROUND: T1 imaging based on pixel-wise quantification of longitudinal
      relaxation has the potential to differentiate between normal and abnormal
      myocardium. The accuracy of T1 measurement has not been established nor
      systematically tested in the presence of health and disease. METHODS: Intra
      observer, inter-observer and inter-study reproducibility of T1 imaging was
      assessed in subjects with left ventricular hypertrophy (LVH, n = 25) or dilated
      cardiomyopathy (DCM, n = 43). Thirty-eight subjects with low-pretest likelihood
      of cardiomyopathy served as a control group. T1 values were acquired in a single
      mid-ventricular short axis slice using modified Look-Locker imaging prior and
      after the application of gadolinium contrast at 1.5 and 3 T. Analysis was
      performed with regions of interest (ROI) placed conservatively within the septum
      or to include the whole short axis (SAX) myocardium. RESULTS: Intra-observer,
      inter-observer and inter-study repeated measurements within the septum showed
      smaller mean differences and narrower 95% confidence intervals than repeated
      short axis ROI measurements. Native T1 values were higher in septal ROIs compared
      with SAX values at both field strengths (1.5 T: 976 +/- 37 vs. 952 +/- 41, p <
      0.01; 3 T: 1108 +/- 67 vs. 1087 +/- 60, p < 0.01). Native T1 values revealed
      significant mean differences between controls and patients with LVH for both
      septal (1.5 T: 26 +/- 9, p < 0.01; 3 T: 50 +/- 13, p < 0.01) and SAX ROIs (1.5 T:
      19 +/- 11, p < 0.05; 3 T: 47 +/- 19, p < 0.05) with greater differences observed
      at 3 T versus 1.5 T field strength. Native T1 values revealed significant mean
      differences between controls and patients with DCM for septal ROI (1.5 T: 29 +/-
      15, p < 0.05; 3 T: 55 +/- 16, p < 0.01) at both 1.5 T and 3 T, but only for SAX
      ROIs at 3 T (49 +/- 17, p < 0.01). There were no significant differences in post
      contrast T1 values or partition coefficient (lambda) between controls and
      patients. CONCLUSION: Conservative septal ROI T1 measurement is a robust
      technique with excellent intra-observer, inter-observer and inter-study
      reproducibility for native and post-contrast T1 value and partition coefficient
      measurements. Moreover, native septal T1 values reveal the greatest difference
      between normal and abnormal myocardium, which is independent of geometrical
      alterations of cardiac chamber and wall thickness. We propose the use of native
      T1 measurements using conservative septal technique as the standardized approach
      to distinguish health from disease assuming diffuse myocardial involvement.

PMID- 24025487
TI  - Filamentous brown algae infected by the marine, holocarpic oomycete Eurychasma
      dicksonii: first results on the organization and the role of cytoskeleton in both
      host and parasite.
AB  - The important role of the cytoskeletal scaffold is increasingly recognized in
      host-pathogen interactions. The cytoskeleton potentially functions as a weapon
      for both the plants defending themselves against fungal or oomycete parasites,
      and for the pathogens trying to overcome the resisting barrier of the plants.
      This concept, however, had not been investigated in marine algae so far. We are
      opening this scientific chapter with our study on the functional implications of
      the cytoskeleton in 3 filamentous brown algal species infected by the marine
      oomycete Eurychasma dicksonii. Our observations suggest that the cytoskeleton is
      involved in host defense responses and in fundamental developmental stages of E.
      dicksonii in its algal host. 

PMID- 24025485
TI  - Vitamin B(12) metabolism during pregnancy and in embryonic mouse models.
AB  - Vitamin B(12) (cobalamin, Cbl) is required for cellular metabolism. It is an
      essential coenzyme in mammals for two reactions: the conversion of homocysteine
      to methionine by the enzyme methionine synthase and the conversion of
      methylmalonyl-CoA to succinyl-CoA by the enzyme methylmalonyl-CoA mutase.
      Symptoms of Cbl deficiency are hematological, neurological and cognitive,
      including megaloblastic anaemia, tingling and numbness of the extremities, gait
      abnormalities, visual disturbances, memory loss and dementia. During pregnancy
      Cbl is essential, presumably because of its role in DNA synthesis and methionine
      synthesis; however, there are conflicting studies regarding an association
      between early pregnancy loss and Cbl deficiency. We here review the literature
      about the requirement for Cbl during pregnancy, and summarized what is known of
      the expression pattern and function of genes required for Cbl metabolism in
      embryonic mouse models.

PMID- 24025488
TI  - Beliefs on epilepsy in Northern Ghana.
AB  - Stigma associated with any chronic disease is one of the greatest challenges to
      the treatment of the disease. Stigma in health is a complex concept, and it
      causes people with a stigmatizing disease to conceal their disorder. Epilepsy is
      one such condition with numerous outdated, sometimes inhumane, and sometimes
      absurd perceptions that tend to fuel its stigma. Health-care workers who
      participated in an epilepsy training program as part of a World Health
      Organization/Ghana Health Service collaboration were asked to compile the
      perceptions associated with epilepsy in their communities. The comments they
      gathered are presented here. 

PMID- 24025489
TI  - [The role of cell adhesion molecules in neurite recognition and synaptogenesis of
      the mammalian nervous system].

PMID- 24025484
TI  - Immunometabolism in obese asthmatics: are we there yet?
AB  - Obesity is now recognised as a worldwide epidemic. The recent International
      Association for the Study of Obesity/International Obesity Taskforce (IASO/IOTF)
      analysis estimates that approximately 1.0 billion adults are currently overweight
      and a further 475 million are obese. Obesity has huge psychosocial impact with
      obese children and adolescents facing discrimination and stigmatization in many
      areas of their lives leading to body dissatisfaction, low self-esteem and
      depression. Indeed, obesity is recognised as an important risk factor for the
      development of several chronic diseases such as hypertension, cancer, asthma and
      metabolic syndrome. Chronic low grade systemic inflammation is considered as a
      hallmark of obesity and may possibly explain the link between obesity and chronic
      disease, in particular the increased incidence, prevalence and severity of asthma
      in obese individuals. There is now strong evidence for infiltration of immune and
      inflammatory cells into adipose tissue that drives systemic inflammation and
      subsequent end organ damage. In addition to adipocytes, the key adipose tissue
      resident immune cells are macrophages and mast cells. Immunometabolism, as an
      emerging field of investigation, explores the pivotal role of these immune cells
      in translating immunological changes to metabolic effects in obesity. Abundance
      of free fatty acids, along with other inflammatory cytokines shift the balance of
      metabolic homeostasis to pro-inflammatory status by influencing the development
      of inflammatory cell lineage, which, further exhibits distinct functional
      phenotypes. There is emerging evidence for macrophage activation and functional
      polarization of an anti-inflammatory M2 phenotype towards a pro-inflammatory M1
      phenotype of macrophages in obese adipose tissue. Similarly, studies in both
      obese humans and murine models reveal the pathognomic presence of an increased
      number of mast cells in visceral adipose tissue. These suggest a possible
      contribution of mast cells to the unique metabolome of obese asthma. This review
      examines proposed multilevel interactions between metabolic and immune systems in
      obese asthmatics that underlie the negative effects of obesity and may offer
      significant therapeutic promise. 

PMID- 24025490
TI  - [Activity-dependent regulation of dendritic spine morphology and brain diseases].

PMID- 24025491
TI  - [Antidepressant and synaptic remodeling by cell adhesion molecules].

PMID- 24025492
TI  - [Drug development targeting synaptic molecules - autism mouse models as an
      example].

PMID- 24025493
TI  - [Toward unraveling cellular mechanisms of long-term memory: structural plasticity
      reproduced in vitro].

PMID- 24025494
TI  - [Life innovation from Kawasaki! Toward the solidification of international
      competitiveness].

PMID- 24025495
TI  - [Pharmacological and clinical profile of a novel DPP-4 inhibitor teneligliptin
      hydrobromide hydrate (TENELIA((r))].

PMID- 24025496
TI  - [TMEM16 as calcium-activated chloride channels].

PMID- 24025497
TI  - [Involvement of membrane receptors in proliferation and differentiation of
      pluripotent stem cells].

PMID- 24025498
TI  - Self-assembled monolayer-based selective modification on polysilicon nanobelt
      devices.
AB  - In this study, a self-assembled monolayer (SAM) of methoxy-poly (ethylene-glycol)
      silane (mPEG-sil) was used to modify the silicon dioxide surface of polysilicon
      nanodevices (PNDs) to act as a passivation layer that inhibits nonspecific
      binding of proteins and reduces localized Joule heating power. Selective
      modifications of 3-aminopropyltrimethoxysilane (APTMS), NHS-biotin and dye
      labeled Streptavidin on the removal regions were characterized. These PNDs, which
      consist of a two-level doping profile, were designed to confine heat in the low
      level doping region during localized Joule heating. Localized Joule heating with
      pulse bias was examined in both vacuum and ambient, which indicated the removal
      region was longer in vacuum for the same pulse bias. Moreover, a comparison of
      selectively and nonselectively modified PNDs observed in time-lapsed fluorescence
      detection of dye-labeled Streptavidin showed a higher increasing rate in
      fluorescence intensity (~2* enhancement) in the selectively modified PNDs.
      Finally, a COMSOL simulation was employed to evaluate the temperature
      distribution in the PNDs, with results showing that heat confinement was observed
      in the low-level doping region and a temperature very close to 673 K was achieved
      while applying a pulse voltage (40 V, 5 MUs) to remove mPEG-sil. 

PMID- 24025499
TI  - [Scientific and rational usage of biologics for the rheumatic diseases: a step
      forward comments on Chinese consensus of etanercept for rheumatoid arthritis and
      ankylosing spondylitis (2013 edition)].

PMID- 24025500
TI  - [Risk factors for in-hospital mortality in patients with acute exacerbation of
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To explore the risk factors for hospitalization case fatality of
      patients with acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD). METHODS: A retrospective review of medical records was performed for
      182 hospitalized AECOPD patients at Nanfang Hospital from January 2010 to August
      2012. Their general information, condition in stable stage, the results of
      spirometry, blood routine test, blood gas analysis and C-reactive protein (CRP)
      were collected and analyzed. The risk factors for mortality were analyzed by
      multivariable Logistic regression. RESULTS: Among them, 42 died during
      hospitalization. Univariate analysis revealed that 8 factors had significant
      differences between two groups (all P < 0.05): high exacerbation risk (death vs
      improvement group, 90.4% vs 70.0%) , low peripheral absolute lymphocyte count
      (73.8% vs 47.1%), high CRP (50.0% vs 17.1%), concurrent anemia (50.0% vs 27.1%),
      hypoproteinemia (71.4% vs 46.4%), hypercapnia (64.3% vs 30.7%), chronic pulmonary
      heart disease (76.1% vs 40.7%) and ischemic heart disease (19.0% vs 7.0%). By
      multiple Logistic regression analysis, high CRP (OR = 3.226, P = 0.009),
      hypercapnia (OR = 2.928, P = 0.013), chronic pulmonary heart disease (OR = 2.510,
      P = 0.045), low peripheral absolute lymphocyte count (OR = 2.488, P = 0.045) were
      the independent risk factors for hospitalization case fatality of AECOPD
      patients. CONCLUSION: Low peripheral absolute lymphocyte count, high CRP,
      hypercapnia and chronic pulmonary heart disease were the independent risk factors
      for mortality in hospitalized AECOPD patients.

PMID- 24025501
TI  - [Platelet factor 4 and beta-thromboglobulin in blood plasma of patients with
      acute exacerbation of chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To explore the role of platelet factor 4 (PF4) and beta
      thromboglobulin (beta-TG) in patients with acute exacerbation of chronic
      obstructive pulmonary disease (AECOPD). METHODS: A total of 71 AECOPD patients
      and 50 chronic obstructive pulmonary disease (COPD) patients within a stable
      stage were admitted into Beijing Chaoyang Hospital from January 2008 to June
      2010. And another 40 healthy volunteers were selected as control group. The data
      of demographics, arterial blood gas analysis and pulmonary function parameters
      was collected and analyzed. The plasma levels of PF4 and beta-TG were measured by
      enzyme-linked immunosorbent assay (ELISA). Platelet count was measured by
      hematology analyzer. Statistical analysis was used for PF4, beta-TG and platelet
      count. Spearman rank correlation was used for correlation analysis. RESULTS: No
      differences in age and gender existed among the AECOPD, stable and control
      groups. The plasma level of PF4 in the AECOPD group (2.28 ug/L) was significantly
      higher than that of the stable group (2.01 ug/L) and control group (1.57 ug/L)
      (both P < 0.05). The level of beta-TG in AECOPD was 2.32 ug/L and it was
      significantly higher than that of the stable group (1.85 ug/L) and control group
      (1.29 ug/L) (both P < 0.05). The differences in platelet counts were
      insignificant between the AEC OPD group ((196 +/- 67) *10(9)/L), stable group
      ((194 +/- 50) *10(9)/L) and control group ((190 +/- 48) *10(9)/L). AECOPD group
      was divided into moderate, severe and very severe groups by pulmonary function
      parameters. The levels of PF4 and beta-TG in very severe group were significantly
      higher than those in moderate and severe groups (P < 0.05). A significant
      positive correlation was observed between PF4 and beta-TG (r = 0.518, P < 0.01).
      The levels of PF4 and beta-TG were negatively correlated with FEV1%, FEV1/FVC and
      PaO2 (all P < 0.05). CONCLUSION: Abnormal platelet activation exists in AECOPD.
      And the levels of PF4 and beta-TG may reflect the severity of AECOPD and can be
      used as the markers of estimating prethrombotic state.

PMID- 24025502
TI  - [Survey on the prevalence rate of bronchial asthma in Beijing area among the
      residents aged over 14 years from 2010 to 2011].
AB  - OBJECTIVE: To survey the prevalence rate of bronchial asthma in Beijing area
      among residents aged over 14 years. METHODS: In accordance with stratified
      cluster random sampling, epidemiological questionnaires were performed in Beijing
      residents aged over 14 years during household visits from February 2010 to August
      2011. Asthma was diagnosed on the basis of case history, clinical signs and lung
      function test. The statistical software SAS 9.2 was employed to analyze the
      epidemiological status of asthma. RESULTS: In a sampling population of 61 107, 57
      647 questionnaires were effective. Among 687 asthmatics, there were 296 males and
      391 females. The overall prevalence rate of asthma was 1.19% (687/57 647). The
      asthma prevalence rates were 1.09% (418/38 468) and 1.40% (269/19 179) in urban
      and suburb Beijing respectively and the prevalence rate of asthma in suburb area
      was significantly higher than that of urban area (chi(2) = 10.850, P = 0.001).
      The prevalence rates of males and females were 1.06% (296/27 947) and 1.32%
      (391/29 700) respectively and the prevalence rate of asthma in females was much
      higher than that of males (chi(2) = 8.098,P = 0.004). Significant differences
      existed among different age groups (chi(2) = 404.874, P = 0.000) and residents
      aged at or over 71 years had the highest prevalence rate. The prevalence rates in
      urban and suburb Beijing area increased by 1.12 and 2.26 folds respectively than
      that of 2002. And 198 asthmatics were first diagnosed in this survey and
      accounted for 28.8% (198/687) in all asthma diagnosed asthmatics. CONCLUSIONS:
      The prevalence rate of asthma in Beijing area among residents aged over 14 years
      increased greatly from 2010 to 2011. And the epidemiological data may reflect the
      current distribution status of asthma in Beijing area.

PMID- 24025503
TI  - [Antimicrobial resistance of Gram-negative bacilli isolated from 13 teaching
      hospitals across China].
AB  - OBJECTIVE: To explore the antimicrobial resistance of nosocomial Gram-negative
      bacilli across China. METHODS: A total of 1247 consecutive and non-repetitive
      Gram-negative bacilli were isolated from 13 Chinese teaching hospitals from March
      to August 2012. All isolates were sent to a central laboratory for
      reidentification and susceptibility testing. The minimal inhibitory concentration
      (MICs) of meropenem and other antibacterial agents were determined by agar
      dilution method. And the data were analyzed with WHONET-5.6 software. RESULTS:
      The activity of antimicrobial agents against Enterobacteriaceae was in the
      following descending order of susceptibility rate: meropenem (97.5%, 849/871) ,
      amikacin (94.5%, 823/871) , imipenem (93.6%, 815/871) , ertapenem (92.9%,
      809/871) , piperacillin/tazobactam (89.9%, 783/871) , cefoperazone/sulbactam
      (83.5%, 727/871) , cefepime (78.1%, 680/871) , polymyxin B (77.0%, 670/871) ,
      cefiazidime (69.6%, 606/871) , levofloxacin (69.2%, 603/871) , ciprofloxacin
      (63.6%, 554/871) , minocyline (63.1%, 550/871) , ceftriaxone (55.7%, 485/871) ,
      cefotaxime (54.2%, 472/871) and cefoxitin (51.4%, 448/871) . The prevalence of
      extended-spectrum beta-lactamase (ESBL) was 64.3% (117/182) in Escherichia coli
      (E. coli) and 32.1% (60/187) in Klebsiella pneumonia (K. pneumoniae) . The
      sensitivities of E. coli to meropenem and imipenem were 100%. And over 90% of E.
      coli was sensitive to ertapenem, amikacin, piperacillin/tazobactam and polymyxin
      B. However, over 60% of E. coli was resistant to ciprofloxacin, levofloxacin,
      ceftriaxone and cefotaxime. The susceptibility of K. pneumoniae to meropenem,
      imipenem, amikacin and polymyxin B maintained at over 90%. The activities of
      antimicrobial agents against E. cloacae, E. aerogenes and Citrobacter freundii
      were in the following descending order of susceptibility rate: meropenem (96.0%
      100%) , imipenem (96.0%-100%) , polymyxin B (95.8%-100%) , amikacin (92.2%-100%)
      , ertapenem (85.6%-93.3%) , cefepime (77.8%-93.3%) , cefoperazone/sulbactam
      (78.4%-90.0%) and piperacillin/tazobactam (65.0%-89.8%) . The most susceptible
      agent against Acinetobacter baumannii (A. baumannii) was polymyxin B (100%) . The
      susceptibilities of A.baumannii to imipenem, meropenem and minocyline were 37.8%
      (65/172) , 36.0% (62/172) and 62.8% (108/172) respectively. The most active
      agents against Pseudomonas aeruginosa (P. aeruginosa) were polymyxin B (97.2%,
      173/178) , followed by amikacin (89.3%, 159/178) and cefiazidime (83.7%, 149/178)
      . Clinical and Laboratory Standards Institute revised P.aeruginosa susceptibility
      standard in 2012. The sensitivity of piperacillin/tazobactam changed from 83.7%
      (149/178) to 77.5% (138/178) . The sensitivity of meropenem decreased from 78.1%
      ( 139/178 ) to 71.3% ( 127/178 ) while that of imipenem declined from 69.7%
      (124/178) to 59.6% (106/178) . The prevalence of multi-drug resistant A.
      baumannii and P. aeruginosa were 65.7% (113/172) and 9.0% (16/178) respectively.
      CONCLUSIONS: Carbapenems remain highly active against Enterobacteriaceae.
      Increasing resistance of A. baumannii to all antimicrobial agents is noted. New
      breakpoint to P.aeruginosa has obvious effects on antimicrobial sensitivity.

PMID- 24025504
TI  - [Clinical paired study of comparing docetaxel plus capecitabine versus docetaxel
      plus epirubicin as first-line treatment in women with HER-2 negative advanced
      breast cancer].
AB  - OBJECTIVE: To assess the efficacy of docetaxel plus capecitabine versus docetaxel
      plus epirubicin as first-line treatment in women with HER-2 negative advanced
      breast cancer. METHODS: A paired study was conducted for 92 cases with HER-2
      negative advanced breast cancer. They received 3 weekly cycles of either TX
      (docetaxel 75 mg/m(2), day 1; capecitabine 1000 mg/m(2) orally twice daily, days
      1-14) or TE (docetaxel 75 mg/m(2), day 1; epirubicin 75 mg/m(2), day 1). The
      objective was to compare 6-month non-progression rate, time to progression (TTP)
      , overall response rate (ORR) and toxicities. RESULTS: The 6-month non
      progression rates were 78% with TX versus 70% with TE (P = 0.477). Medium TTP was
      10.2 versus 8.7 months (P = 0.128) and ORR was 72% and 63% respectively (P =
      0.505) . Severe toxicities included hand-foot syndrome (37% vs 4%, P < 0.001),
      grade 3-4 neutropenia (30% vs 70%, P < 0.001) and febrile neutropenia (2% vs 11%,
      P = 0.004) respectively. No relevant differences in other toxicities were
      observed in two arms. CONCLUSION: Both regimens of TX and TE have similar
      efficacy and are well-tolerated as the first-line therapy for HER-2 negative
      advanced breast cancer.

PMID- 24025505
TI  - [Efficacy and safety of vitamin D for type 2 diabetes mellitus: a systematic
      review].
AB  - OBJECTIVE: To evaluate the efficacy and safety of vitamin D (VD) for patients
      with type 2 diabetes mellitus. METHODS: Randomized controlled trials (RCT) were
      identified from CBM (1978.1-2012.9), CNKI (1979.1-2012.9), Pubmed (1950.1
      2012.9), EMbase (1970.1-2012.9) and Cochrane library (issue 4, 2012).
      Publications of the RCT on the treatment of type 2 diabetes mellitus with VD were
      included and analyzed according to the criteria of Cochrane handbook. RESULTS:
      Six RCT involving 328 patients were included. Meta-analysis indicated that VD
      caused a reduction in glycosylated hemoglobin A 1c (HbA 1c) (P = 0.05) but not in
      fasting plasma glucose (FPG), homeostasis model assessment index of insulin
      resistance (HOMA-IR) and failed to improve quantitative insulin sensitivity check
      index (QUICKI) and homeostasis model assessment index of beta cell function (HOMA
      beta) (P > 0.05). As reported in a trial, the side effect of VD was
      hypercalcemia. CONCLUSION: VD may have positive effects on patients with type 2
      diabetes mellitus. However, the evidence is weak due to the general low
      methodological quality. Thus we have not made a reliable conclusion about the
      effects of VD for type 2 diabetes mellitus at the moment. Further larger,
      randomized, double-blind, placebo-controlled and multicenter trials are
      warranted.

PMID- 24025506
TI  - [Anti-apoptotic mechanism for p21(waf1) in human basal like breast cancer cell
      line HCC1937].
AB  - OBJECTIVE: To explore the anti-apoptotic mechanism of p21(waf1) in human basal
      like breast cancer cell line HCC1937. METHODS: There were 3 groups, i.e.
      experimental group HCC1937 with lentivirus -p21(waf1)-shRNA-RFP, control group 1
      HCC1937 without lentivirus and control group 2 HCC1937 with lentivirus -RFP. The
      p21(waf1) and bim mRNA and protein expressions were detected by reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot respectively.
      And apoptosis of HCC1937 in different groups was assayed by terminal
      deoxynucleotidyl transferase mediated C-dUTP nick end labeling (TUNEL). RESULTS:
      After interference with lentivirus-p21(waf1)-shRNA-RFP, p21(waf1) mRNA and
      protein expressions declined significantly in the experimental group versus the
      control groups (experiment group: 0.260 +/- 0.004, 0.293 +/- 0.006, control group
      1: 0.879 +/- 0.028, 0.483 +/- 0.071, control group 2: 0.870 +/- 0.025, 0.469 +/-
      0.047, all P < 0.01). The bim mRNA and protein expressions increased. And there
      was significant difference between the experiment and control groups (experiment
      group: 0.420 +/- 0.013, 0.355 +/- 0.007, control group 1: 0.258 +/- 0.005, 0.142
      +/- 0.012, control group 2: 0.259 +/- 0.002, 0.147 +/- 0.013, all P < 0.001);
      apoptotic index increased (experiment group: 0.279 +/- 0.012, control group 1:
      0.145 +/- 0.008, control group 2: 0.148 +/- 0.012, both P < 0.001). CONCLUSION:
      In human basal-like breast cancer cell line HCC1937, p21(waf1) exerts anti
      apoptotic activity by inhibiting the expression of bim, a mediator of
      mitochondrial apoptosis.

PMID- 24025507
TI  - [Clinicopathological features and multivariate analysis of prognostic factors for
      patients with gastroenteropancreatic neuroendocrine tumors].
AB  - OBJECTIVE: To analyze the clinicopathologic characteristics of
      gastroenteropancreatic neuroendocrine neoplasm(GEP-NET) and explore the
      prognostic factors for patients with GEP-NET. METHODS: Retrospectively reviews
      were conducted for the charts of 68 patients diagnosed pathologically with GEP
      NET and treated at Sichuan Cancer Hospital during January 2001 to June 2012. The
      information of prognostic factors was retrieved and analyzed. Kaplan-Meier method
      was used to estimate survival rates and plot patient survival curves of patients
      at different levels of predictive factors. The association between
      clinicopathologic characteristic and prognosis in GEP-NET patients was assessed
      with Log-rank test. Meanwhile Cox proportional hazard model was used to select
      independent risk factors of patient survival. RESULTS: Stomach (20/68,29.41%) and
      cardia (16/68,23.53%) were mostly involved. Frequent tumor sites for males were
      stomach and cardia (34/52,65.38%) while the most common site was intestinal canal
      for female (12/16) . Ages of disease onset were different significantly among
      patient groups of different sites (P = 0.023). The average age of intestinal NET
      was the highest while gastric NET had the lowest. During a median follow-up
      duration of 49 (3-120)months, there were 37 deaths (54.41%), including 30 from
      postoperative relapses. Postoperative survival time ranged from 4-115 months. The
      mean survival periods were (46 +/- 7) months respectively. The 1, 3, and 5-year
      survival rates were 65.1%, 41.5% and 28.7% respectively. Univariate analyses
      showed that the risk factors of survival time were patient age over 60 years,
      tumor size > 2 cm, T2-4 stage of tumor, vascular invasion, lymph node metastasis,
      distant metastasis, positive surgical margin and pathological grades of
      neuroendocrine carcinoma (NEC) and mixed adenoneuroendocrine carcinoma (MANEC).
      Multivariate analysis indicated independent risk factors were tumor size > 2 cm
      and pathological grades of NEC and MANEC. CONCLUSIONS: GEP-NET may occur at
      multiple sites of digestive system and lack specific clinical manifestations.
      Tumor size, distant metastasis and pathological grades were independent
      prognostic factors for GEP-NET patients.

PMID- 24025508
TI  - [Clinicopathological characteristics and prognostic factors of 27 patients with
      rectal gastrointestinal stromal tumors].
AB  - OBJECTIVE: To explore the clinicopathological characteristics of rectal
      gastrointestinal stromal tumors (GISTs) and elucidate their associated prognostic
      factors. METHODS: The clinicopathological data were collected for 27 patients
      with rectal gastrointestinal stromal tumors at our hospital from January 2000 to
      December 2011. Univariate analyses were performed to evaluate the prognostic
      factors. RESULTS: Changed habit of discharge and hematochezia were the most
      common symptoms. Most GISTs were localized in lower rectum. The 1, 3 and 5-year
      progression-free survival (PFS) rates were 85.19%, 65.04% and 52.04%
      respectively. Overall survival (OS) and PFS rates were significantly correlated
      with incisional margin and invasion of surrounding organs. There was no
      significant difference in PFS and OS between different resection procedures.Due
      to the limitation of cases multivariate survival analysis can not be performed.
      CONCLUSION: Incisional margin and invasion of surrounding organs are two
      important prognostic factors. And transanal excision is both safe and effective
      for those properly indicated patients.

PMID- 24025509
TI  - [Ultrasound-aided biodegradable osteosynthesis system: application in fixation of
      oral and maxillofacial fractures].
AB  - OBJECTIVE: To evaluate the effectiveness and complications of an ultrasound-aided
      biodegradable osteosynthesis system in the treatment of midfacial fractures.
      METHODS: From January 1, 2010 to March 1, 2013, a total of 193 midfacial
      fractures patients were recruited. There were 120 males and 73 females. Among
      them, 93 patients were treated with SonicWeld Rx system (KLS Martin, Tuttlingen,
      Germany) while 100 patients FIXSORB MX (Takiron Co., Ltd, Osaka, Japan). The
      effectiveness, short-term and long-term complications were assessed by clinical
      examinations and computed tomography during an average follow-up period of 18
      months. RESULTS: All fractures healed well without dislocation, malunion, delayed
      union or nonunion. Pin insertion was completed with a total success rate of 99%
      in SonicWeld Rx group versus 98% in FIXSORB MX group. Three patients in SonicWeld
      Rx group and 2 in FIXSORB MX group developed postoperative local inflammation and
      healed with antibiotics therapy. Hardware visibility or palpability occurred in 3
      and 8 patients in two groups respectively. One patient in SonicWeld Rx group and
      4 in FIXSORB MX group experienced sterile abscess at Months 12-15 postoperatively
      and resolved by the removal of biodegradable materials. Two cases of implant
      looseness were observed in FIXSORB MX group. No other procedure-related
      complication was noted in either group. CONCLUSION: The ultrasound-aided
      biodegradable osteosynthesis of SonicWeld Rx system is both effective and safe in
      the treatment of midfacial fractures. And its complication rate is equal to that
      of traditional biodegradable fixation.

PMID- 24025510
TI  - [Clinicopathological features of Wilson disease: report of 29 cases].
AB  - OBJECTIVE: To summarize the clinicopathological manifestations of Wilson
      disease(WD) so as to improve its recognition. METHODS: A total of 29 WD cases
      were retrospectively analyzed, including clinical presentations, liver function
      test, serum ceruloplasmin, 24 hour urinary copper excretion, ATP7B gene analysis
      and liver histology. All cases were diagnosed from January 2007 to October 2012
      at Third Hospital of Hebei Medical University and China-Japan Friendship
      Hospital. RESULTS: There were 18 males and 11 females with an average age of 25.9
      years. The major clinical symptoms included fatigue (n = 18, 62.1%), abdominal
      distension (n = 4,13.8%) and pruritus (n = 4, 13.8%). The common physical signs
      were hepatomegaly (n = 11, 37.9%), splenomegaly(n = 15, 51.7%) and ascites (n =
      4, 13.8%). The laboratory examinations included abnormal liver function (n = 29,
      100%), high level of 24-hour urinary copper excretion (n = 29, 100.0%), low serum
      ceruloplasmin (n = 24, 82.8%) and Kayser-Fleischer ring (n = 8, 27.6%). ATP7B
      gene mutations were at exons 5, 8, 11, 12, 16 and 18. The earliest histologic
      abnormalities of liver included steatosis (both microvesicular and
      macrovesicular). Timm's stain showed positive or negative staining. There was no
      or focal hepatocellular necrosis in liver. During chronic hepatitis phase, the
      major changes included inflammatory cells infiltration in portal area with
      biliary epithelium degeneration. The periportal area hepatic cells were swollen,
      cytoplasm slightly stained and accompanied with some copper particles deposition
      and cholestic changes. There were many spotty or focal lesion of necrosis in
      liver. During cirrhotic phase, portal area became enlarged by fibrotic tissue,
      numerous copper particles deposited in wide fibrous septa and small bile ducts
      were damaged and became proliferative. Hepatocytes around fibrous interval showed
      cholestatic changes and contained many copper particles. They diagnosed on the
      basis of clinical presentation(n = 6), clinical presentation and liver histology
      (n = 4) and clinical presentation, liver histology and gene analysis (n = 19).
      CONCLUSIONS: There is a high misdiagnosis rate of WD based solely on clinical
      presentation. Cholestic changes around fibrous interval are common histologic
      features. The most common ATP7B gene mutations are compound heterozygotes in
      exons 16. Comprehensive evaluations of clinical presentation, liver histology and
      gene analysis are helpful for early diagnosis and timely treatment so that it
      helps to reduce the misdiagnosis and missed diagnosis rate of WD.

PMID- 24025511
TI  - [Molecular mechanism and effect of microRNA185 on proliferation, migration and
      invasion of esophageal squamous cell carcinoma].
AB  - OBJECTIVE: To explore the role and mechanism of microRNA185 (miR-185) on
      proliferation, migration and invasion of esophageal squamous cell carcinoma
      (ESCC). METHODS: Samples were obtained from 23 ESCC patients undergoing surgery
      whose were confirmed by pathological diagnosis of esophageal carcinoma from 2002
      to 2012,at Department of Thoracic Surgery,Cancer Institute and Cancer Hospital,
      Chinese Academy of Medical Sciences and Peking Union Medical College. Real-time
      PCR was used to measure the expression of miR-185. The xCELLigence RTCA MP system
      and Transwell assay were performed to detect the effect of miR-185 on
      proliferation, migration and invasion of ESCC respectively. After transfecting of
      miR-185 mimic into KYSE150, the expression of Six1's downstream gene cyclin A1
      was evaluated by real-time PCR. After transfection of miR-185 inhibitor into
      KYSE30, the expression of E-cadherin, a downstream protein of Six1, was observed
      under confocal microscope. RESULTS: The expression level of miR-185 was down
      regulated in ESCC compared with adjacent normal tissue (0.006 vs 0.039,P =
      0.016). After transfection of miR-185 mimic, miR-185 significantly inhibited
      proliferation, migration and invasion of ESCC.Transwell assay showed, in
      comparison with the control group, the number of KYSE150 metastatic and invasive
      cells was respectively decreased(146 +/- 15 vs 64 +/- 11, 110 +/- 12 vs 67 +/- 5,
      both P < 0.05). And the expression level of cyclin A1 decreased. After
      transfection of miR-185 inhibitor,the expression level of E-cadherin decreased.
      CONCLUSION: miR-185 may inhibit proliferation, migration and invasion of ESCC
      through its target gene Six1.

PMID- 24025512
TI  - [APPL1-mediated effects of leptin on activity of GSK-3beta in C2C12 cell].
AB  - OBJECTIVE: To observe the effects of leptin on activity of GSK-3beta and explore
      its mechanism. METHODS: C2C12 myoblasts differentiated for 3 days into myotubes
      in differentiation medium. Myotubes were stimulated by leptin (100 nmol/L) for 0,
      5, 15 or 30 min respectively. Western blot was used to detect the expression
      levels of GSK-3beta and phospho-GSK-3beta (ser-9). Co-immunoprecipitation (CO-IP)
      was performed to determine the relationship among APPL1, leptin receptor and GSK
      3beta in the presence or absence of leptin. The expression level of GSK-3beta at
      phospho-GSK-3beta (ser-9) was detected in APPL1-suppressed C2C12 myotube while
      that of APPL1 at phospho-APPL1 (ser-401) determined in GSK-3beta
      overexpressed/inhibited C2C12 cell. RESULTS: Leptin time-dependently increased
      the phosphorylation level of GSK-3beta at ser-9 in C2C12 cell, and the pGSK-3beta
      level in cells incubated by leptin for 30 min was as 4.08 times as which in
      control cells (P < 0.01). The triple complex of APPL1, leptin receptor and GSK
      3beta, in the presence of leptin, the binding capacity between APPL1 and GSK
      3beta was stronger. The level of phospho-GSK-3beta was significantly lower in
      APPL1-suppressed C2C12 cell compared with that in control cells. And the
      phosphorylation of APPL1 at ser-401 could be induced by GSK-3beta. CONCLUSION:
      Leptin promotes muscle glycogen synthesis by inducing phosphorylation of GSK
      3beta in C2C12 cell. Such a function may be mediated by the triple complex of
      APPL1, leptin receptor and GSK-3beta. Meanwhile, GSK-3beta can also increase the
      phosphorylation of APPL1 at ser-401.

PMID- 24025513
TI  - Text classification for assisting moderators in online health communities.
AB  - OBJECTIVES: Patients increasingly visit online health communities to get help on
      managing health. The large scale of these online communities makes it impossible
      for the moderators to engage in all conversations; yet, some conversations need
      their expertise. Our work explores low-cost text classification methods to this
      new domain of determining whether a thread in an online health forum needs
      moderators' help. METHODS: We employed a binary classifier on WebMD's online
      diabetes community data. To train the classifier, we considered three feature
      types: (1) word unigram, (2) sentiment analysis features, and (3) thread length.
      We applied feature selection methods based on chi2 statistics and under sampling
      to account for unbalanced data. We then performed a qualitative error analysis to
      investigate the appropriateness of the gold standard. RESULTS: Using sentiment
      analysis features, feature selection methods, and balanced training data
      increased the AUC value up to 0.75 and the F1-score up to 0.54 compared to the
      baseline of using word unigrams with no feature selection methods on unbalanced
      data (0.65 AUC and 0.40 F1-score). The error analysis uncovered additional
      reasons for why moderators respond to patients' posts. DISCUSSION: We showed how
      feature selection methods and balanced training data can improve the overall
      classification performance. We present implications of weighing precision versus
      recall for assisting moderators of online health communities. Our error analysis
      uncovered social, legal, and ethical issues around addressing community members'
      needs. We also note challenges in producing a gold standard, and discuss
      potential solutions for addressing these challenges. CONCLUSION: Social media
      environments provide popular venues in which patients gain health-related
      information. Our work contributes to understanding scalable solutions for
      providing moderators' expertise in these large-scale, social media environments.

PMID- 24025515
TI  - Long term durability of radon remedial measures in a sample of UK homes.
AB  - A study to determine the long term effectiveness of commonly used radon remedial
      methods over a 15 year period is discussed. The overall failure rate for
      remediation systems was 63%, with roughly equal rates for passive and active type
      systems. The fans used in active systems performed better than expected, with
      many of them exceeding manufacturers' stated life spans by several years. The
      study found that all types of remedial measure can last more than ten years, but
      also found examples for all measures that failed in less than five years. This
      supports HPA advice that homes should be retested every 5-10 years. It was also
      noted that householders found it difficult to detect failures in passive systems.
      The need for a follow-up study is discussed, in light of likely changes in
      building practices and materials during the last twenty years.

PMID- 24025514
TI  - Comparative analysis of seed transcriptomes of ambient ozone-fumigated 2
      different rice cultivars.
AB  - High ozone (O3) concentrations not only damage plant life but also cause
      considerable losses in plant productivity. To screen for molecular factors usable
      as potential biomarkers to identify for O3-sensitive and -tolerant lines and
      design O3 tolerant crops, our project examines the effects of O3 on rice, using
      high-throughput omics approaches. In this study, we examined growth and yield
      parameters of 4 rice cultivars fumigated for a life-time with ambient air (mean
      O3: 31.4-32.7 ppb) or filtered air (mean O3: 6.6-8.3 ppb) in small open-top
      chambers (sOTCs) to select O3-sensitive (indica cv Takanari) and O3-tolerant
      (japonica cv Koshihikari) cultivars for analysis of seed transcriptomes using
      Agilent 4 * 44K rice oligo DNA chip. Total RNA from dry mature dehusked seeds of
      Takanari and Koshihikari cultivars was extracted using a modified protocol based
      on cethyltrimethylammonium bromide extraction buffer and phenol-chloroform
      isoamylalcohol treatment, followed by DNA microarray analysis using the
      established dye-swap method. Direct comparison of Koshihikari and Takanari O3
      transcriptomes in seeds of rice plants fumigated with ambient O3 in sOTCs
      successfully showed that genes encoding proteins involved in jasmonic acid, GABA
      biosynthesis, cell wall and membrane modification, starch mobilization, and
      secondary metabolite biosynthesis are differently regulated in sensitive cv
      Takanari and tolerant cv Koshihikari. MapMan analysis further mapped the
      molecular factors activated by O3, confirming Takanari is rightly classified as
      an O3 sensitive genotype.

PMID- 24025516
TI  - Rapamycin increases survival in ALS mice lacking mature lymphocytes.
AB  - BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a devastating progressive
      neurodegenerative disease. Disease pathophysiology is complex and not yet fully
      understood, but is proposed to include the accumulation of misfolded proteins, as
      aggregates are present in spinal cords from ALS patients and in ALS model
      organisms. Increasing autophagy is hypothesized to be protective in ALS as it
      removes these aggregates. Rapamycin is frequently used to increase autophagy, but
      is also a potent immune suppressor. To properly assess the role of rapamycin
      induced autophagy, the immune suppressive role of rapamycin should be negated.
      FINDINGS: Autophagy is increased in the spinal cord of ALS mice. Dietary
      supplementation of rapamycin increases autophagy, but does not increase the
      survival of mutant SOD1 mice. To measure the effect of rapamycin in ALS
      independent of immunosuppression, we tested the effect of rapamycin in ALS mice
      deficient of mature lymphocytes. Our results show that rapamycin moderately
      increases the survival of these ALS mice deficient of mature lymphocytes.
      CONCLUSIONS: Rapamycin could suppress protective immune responses while enhancing
      protective autophagy reactions during the ALS disease process. While these
      opposing effects can cancel each other out, the use of immunodeficient mice
      allows segregation of effects. Our results indicate that maximal therapeutic
      benefit may be achieved through the use of compounds that enhance autophagy
      without causing immune suppression.

PMID- 24025518
TI  - International Society of Urological Pathology (ISUP) consensus conference on
      renal neoplasia: rationale and organization.

PMID- 24025517
TI  - A BK (Slo1) channel journey from molecule to physiology.
AB  - Calcium and voltage-activated potassium (BK) channels are key actors in cell
      physiology, both in neuronal and non-neuronal cells and tissues. Through negative
      feedback between intracellular Ca (2+) and membrane voltage, BK channels provide
      a damping mechanism for excitatory signals. Molecular modulation of these
      channels by alternative splicing, auxiliary subunits and post-translational
      modifications showed that these channels are subjected to many mechanisms that
      add diversity to the BK channel alpha subunit gene. This complexity of
      interactions modulates BK channel gating, modifying the energetic barrier of
      voltage sensor domain activation and channel opening. Regions for voltage as well
      as Ca (2+) sensitivity have been identified, and the crystal structure generated
      by the 2 RCK domains contained in the C-terminal of the channel has been
      described. The linkage of these channels to many intracellular metabolites and
      pathways, as well as their modulation by extracellular natural agents, has been
      found to be relevant in many physiological processes. This review includes the
      hallmarks of BK channel biophysics and its physiological impact on specific cells
      and tissues, highlighting its relationship with auxiliary subunit expression. 

PMID- 24025523
TI  - Loss of CDX2/CK20 expression is associated with poorly differentiated carcinoma,
      the CpG island methylator phenotype, and adverse prognosis in microsatellite
      unstable colorectal cancer.
AB  - Several previous studies have demonstrated that the CDX2-negative (CDX2) and/or
      CK20-negative (CK20) phenotypes of colorectal cancers (CRCs) might be associated
      with high levels of microsatellite instability (MSI-H). The aim of this study was
      to investigate the clinicopathologic and molecular features of MSI-H CRCs with
      different CDX2/CK20 expression statuses. The CDX2 and CK20 expression statuses
      were immunohistochemically evaluated in 109 MSI-H CRC tissue samples, and the
      correlations of these statuses with clinicopathologic, molecular, and survival
      data were statistically analyzed. Of the 109 MSI-H CRCs, 15 were CDX2 (13.8%),
      and 19 were CK20 (17.4%). The simultaneous loss of CDX2 and CK20 expression
      (CDX2/CK20) was observed in 9 cases (8.3%). CDX2 loss was correlated with lymph
      node metastasis, poor differentiation, MLH1 loss, the mutation of BRAF, and CpG
      island methylator phenotype-high (CIMP-H) status. Right-sided tumor location,
      nodal metastasis, poor differentiation, and CIMP-H status were significant
      characteristics of CK20 tumors. The CDX2/CK20 phenotype was associated with older
      age (above 56 y), higher stage (stage III or IV), deep invasion (pT3 or pT4),
      lymph node metastasis (pN1 or pN2), poor differentiation (nonmedullary/non-signet
      ring cell type), the mutation of BRAF, and CIMP-H status among MSI-H CRCs.
      Patients with CDX2/CK20 tumors exhibited worse overall and disease-free survival
      compared with the patients with CDX2 and/or CK20 tumors (P<0.001). In the
      multivariate analysis for disease-free survival, the CDX2/CK20 phenotype was an
      independent prognostic factor for MSI-H CRC (P=0.030, hazard ratio=3.288). The
      CDX2/CK20 phenotype defines a distinct subgroup of MSI-H CRCs with poor
      differentiation, CIMP-H status, and unfavorable prognosis. 

PMID- 24025521
TI  - Handling and staging of renal cell carcinoma: the International Society of
      Urological Pathology Consensus (ISUP) conference recommendations.
AB  - The International Society of Urologic Pathology 2012 Consensus Conference on
      renal cancer, through working group 3, focused on the issues of staging and
      specimen handling of renal tumors. The conference was preceded by an online
      survey of the International Society of Urologic Pathology members, and the
      results of this were used to inform the focus of conference discussion. On formal
      voting a >=65% majority was considered a consensus agreement. For specimen
      handling it was agreed that with radical nephrectomy specimens the initial cut
      should be made along the long axis and that both radical and partial nephrectomy
      specimens should be inked. It was recommended that sampling of renal tumors
      should follow a general guideline of sampling 1 block/cm with a minimum of 3
      blocks (subject to modification as needed in individual cases). When measuring a
      renal tumor, the length of a renal vein/caval thrombus should not be part of the
      measurement of the main tumor mass. In cases with multiple tumors, sampling
      should include at a minimum the 5 largest tumors. There was a consensus that
      perinephric fat invasion should be determined by examining multiple perpendicular
      sections of the tumor/perinephric fat interface and by sampling areas suspicious
      for invasion. Perinephric fat invasion was defined as either the tumor touching
      the fat or extending as irregular tongues into the perinephric tissue, with or
      without desmoplasia. It was agreed upon that renal sinus invasion is present when
      the tumor is in direct contact with the sinus fat or the loose connective tissue
      of the sinus, clearly beyond the renal parenchyma, or if there is involvement of
      any endothelium-lined spaces within the renal sinus, regardless of the size. When
      invasion of the renal sinus is uncertain, it was recommended that at least 3
      blocks of the tumor-renal sinus interface should be submitted. If invasion is
      grossly evident, or obviously not present (small peripheral tumor), it was agreed
      that only 1 block was needed to confirm the gross impression. Other
      recommendations were that the renal vein margin be considered positive only when
      there is adherent tumor visible microscopically at the actual margin. When a
      specimen is submitted separately as "caval thrombus," the recommended sampling
      strategy is to take 2 or more sections to look for the adherent caval wall
      tissue. It was also recommended that uninvolved renal parenchyma be sampled by
      including normal parenchyma with tumor and normal parenchyma distant from the
      tumor. There was consensus that radical nephrectomy specimens should be examined
      for the purpose of identifying lymph nodes by dissection/palpation of the fat in
      the hilar area only; however, it was acknowledged that lymph nodes are found in
      <10% of radical nephrectomy specimens. 

PMID- 24025524
TI  - Characterization of perineural invasion as a component of colorectal cancer
      staging.
AB  - Perineural invasion (PN) in colorectal cancer (CRC) is a site-specific prognostic
      marker, as mentioned by the AJCC Cancer Staging Manual, but it remains to be
      clearly defined. We aimed to identify an optimal characterization of PN as a
      component of cancer staging. On the basis of the anatomic features of the nervous
      system of the large bowel, site-specific pathologic criteria were assigned to PN
      according to the location of PN. Multi-institutional pathologic review based on
      these criteria was performed for 962 patients with stage I to III CRC at 2
      institutions (1999 to 2004, cohort 1) and 1883 patients from 8 other institutions
      (2000 to 2004, cohort 2). In cohort 1, intramural and extramural PN were observed
      in 152 and 101 patients, respectively, which had a different impact on disease
      free survival (hazard ratio, 2.6 [1.9 to 3.5] vs. 4.7 [3.4 to 6.5],
      respectively). A 3-tiered grading system (Pn0; Pn1a, intramural PN; Pn1b,
      extramural PN) distinguished 5-year disease-free survival as 88%, 70%, and 48%,
      respectively; and multivariate analysis identified PN grade as a significant
      prognostic marker independent of T or N stage. These results were similar in
      cohort 2. Interinstitutional difference of the prognostic impact of PN grade was
      acceptably small among all institutions. Interobserver study among 6
      gastrointestinal pathologists showed superior judgment reproducibility for PN
      compared with vascular invasion. The results of our study indicate that PN is an
      important prognostic marker in CRC. The value of cancer staging could be enhanced
      by PN assessment using site-specific criteria and a simple grading system based
      on PN location within the bowel. 

PMID- 24025519
TI  - The International Society of Urological Pathology (ISUP) Vancouver Classification
      of Renal Neoplasia.
AB  - The classification working group of the International Society of Urological
      Pathology consensus conference on renal neoplasia was in charge of making
      recommendations regarding additions and changes to the current World Health
      Organization Classification of Renal Tumors (2004). Members of the group
      performed an exhaustive literature review, assessed the results of the
      preconference survey and participated in the consensus conference discussion and
      polling activities. On the basis of the above inputs, there was consensus that 5
      entities should be recognized as new distinct epithelial tumors within the
      classification system: tubulocystic renal cell carcinoma (RCC), acquired cystic
      disease-associated RCC, clear cell (tubulo) papillary RCC, the MiT family
      translocation RCCs (in particular t(6;11) RCC), and hereditary leiomyomatosis RCC
      syndrome-associated RCC. In addition, there are 3 rare carcinomas that were
      considered as emerging or provisional new entities: thyroid-like follicular RCC;
      succinate dehydrogenase B deficiency-associated RCC; and ALK translocation RCC.
      Further reports of these entities are required to better understand the nature
      and behavior of these highly unusual tumors. There were a number of new concepts
      and suggested modifications to the existing World Health Organization 2004
      categories. Within the clear cell RCC group, it was agreed upon that multicystic
      clear cell RCC is best considered as a neoplasm of low malignant potential. There
      was agreement that subtyping of papillary RCC is of value and that the oncocytic
      variant of papillary RCC should not be considered as a distinct entity. The
      hybrid oncocytic chromophobe tumor, which is an indolent tumor that occurs in 3
      settings, namely Birt-Hogg-Dube Syndrome, renal oncocytosis, and as a sporadic
      neoplasm, was placed, for the time being, within the chromophobe RCC category.
      Recent advances related to collecting duct carcinoma, renal medullary carcinoma,
      and mucinous spindle cell and tubular RCC were elucidated. Outside of the
      epithelial category, advances in our understanding of angiomyolipoma, including
      the epithelioid and epithelial cystic variants, were considered. In addition, the
      apparent relationship between cystic nephroma and mixed epithelial and stromal
      tumor was discussed, with the consensus that these tumors form a spectrum of
      neoplasia. Finally, it was thought that the synovial sarcoma should be removed
      from the mixed epithelial and mesenchymal category and placed within the sarcoma
      group. The new classification is to be referred to as the International Society
      of Urological Pathology Vancouver Classification of Renal Neoplasia. 

PMID- 24025525
TI  - Primary cutaneous adenoid cystic carcinoma: a clinicopathologic and
      immunohistochemical study of 27 cases.
AB  - AIMS: This study examines clinical and pathologic features of primary cutaneous
      adenoid cystic carcinoma (ACC), with emphasis on biological behavior of these
      tumors. A total of 27 cases of primary cutaneous ACC with detailed follow-up
      information were evaluated. Clinically, these were solitary, slow-growing
      lesions, half of which were in the head and neck area. The median age was 62
      years with a male predilection. Surgical excision was the treatment of choice.
      Histologically, the lesions were similar to those seen in the salivary glands.
      Tumors were classified as grade 1 (17), grade 2 (3), and grade 3 (7). The mitotic
      count was generally low (mean=1.9/mm), except in 2 high-grade tumors (>10 mitotic
      figures/mm). Sixteen cases showed perineural invasion. Immunohistochemically,
      cytokeratin positivity was noted in 13/13 cases, and CD117 was observed in 10/10
      cases, with luminal/cytoplasmic staining for epithelial membrane antigen (14/16)
      and at least focal luminal expression for carcinoembryonic antigen (11/16),
      smooth muscle actin (10/13), and S100 staining (9/13). Eighteen cases had follow
      up data (median 54 mo), 9 of which had local recurrences (50%). Three cases
      showed metastatic disease. No statistical difference was noted between tumor
      grade and local recurrence (P=0.77). Primary cutaneous ACC is a distinct entity
      with a more indolent behavior compared with its salivary counterpart. The
      cutaneous lesions tend to recur locally but have a low metastatic potential.

PMID- 24025520
TI  - The International Society of Urological Pathology (ISUP) grading system for renal
      cell carcinoma and other prognostic parameters.
AB  - The International Society of Urological Pathology 2012 Consensus Conference made
      recommendations regarding classification, prognostic factors, staging, and
      immunohistochemical and molecular assessment of adult renal tumors. Issues
      relating to prognostic factors were coordinated by a workgroup who identified
      tumor morphotype, sarcomatoid/rhabdoid differentiation, tumor necrosis, grading,
      and microvascular invasion as potential prognostic parameters. There was
      consensus that the main morphotypes of renal cell carcinoma (RCC) were of
      prognostic significance, that subtyping of papillary RCC (types 1 and 2) provided
      additional prognostic information, and that clear cell tubulopapillary RCC was
      associated with a more favorable outcome. For tumors showing sarcomatoid or
      rhabdoid differentiation, there was consensus that a minimum proportion of tumor
      was not required for diagnostic purposes. It was also agreed upon that the
      underlying subtype of carcinoma should be reported. For sarcomatoid carcinoma, it
      was further agreed upon that if the underlying carcinoma subtype was absent the
      tumor should be classified as a grade 4 unclassified carcinoma with a sarcomatoid
      component. Tumor necrosis was considered to have prognostic significance, with
      assessment based on macroscopic and microscopic examination of the tumor. It was
      recommended that for clear cell RCC the amount of necrosis should be quantified.
      There was consensus that nucleolar prominence defined grades 1 to 3 of clear cell
      and papillary RCCs, whereas extreme nuclear pleomorphism or sarcomatoid and/or
      rhabdoid differentiation defined grade 4 tumors. It was agreed upon that
      chromophobe RCC should not be graded. There was consensus that microvascular
      invasion should not be included as a staging criterion for RCC. 

PMID- 24025526
TI  - Hemosiderotic fibrolipomatous tumor, not an entirely benign entity.

PMID- 24025522
TI  - Renal tumors: diagnostic and prognostic biomarkers.
AB  - The International Society of Urological Pathology convened a consensus conference
      on renal cancer, preceded by an online survey, to address issues relating to the
      diagnosis and reporting of renal neoplasia. In this report, the role of
      biomarkers in the diagnosis and assessment of prognosis of renal tumors is
      addressed. In particular we focused upon the use of immunohistochemical markers
      and the approach to specific differential diagnostic scenarios. We enquired
      whether cytogenetic and molecular tools were applied in practice and asked for
      views on the perceived prognostic role of biomarkers. Both the survey and
      conference voting results demonstrated a high degree of consensus in
      participants' responses regarding prognostic/predictive markers and molecular
      techniques, whereas it was apparent that biomarkers for these purposes remained
      outside the diagnostic realm pending clinical validation. Although no individual
      antibody or panel of antibodies reached consensus for classifying renal tumors,
      or for confirming renal metastatic disease, it was noted from the online survey
      that 87% of respondents used immunohistochemistry to subtype renal tumors
      sometimes or occasionally, and a majority (87%) used immunohistochemical markers
      (Pax 2 or Pax 8, renal cell carcinoma [RCC] marker, panel of pan-CK, CK7,
      vimentin, and CD10) in confirming the diagnosis of metastatic RCC. There was
      consensus that immunohistochemistry should be used for histologic subtyping and
      applied before reaching a diagnosis of unclassified RCC. At the conference, there
      was consensus that TFE3 and TFEB analysis ought to be requested when RCC was
      diagnosed in a young patient or when histologic appearances were suggestive of
      the translocation subtype; whereas Pax 2 and/or Pax 8 were considered to be the
      most useful markers in the diagnosis of a renal primary. 

PMID- 24025527
TI  - EWSR1 rearrangements in sclerosing epithelioid fibrosarcoma.

PMID- 24025528
TI  - Strength retention behavior of oriented PLLA, 96L/4D PLA, and 80L/20D,L PLA.
AB  - The strength retention characteristics of oriented semicrystalline polylactides
      were monitored during hydrolytic degradation in vitro. The effects of the polymer
      type, the material's initial inherent viscosity (iv), the sample diameter and the
      residual monomer content on strength retention were analyzed. The analyzed
      polylactides had similar, but not identical, strength retention characteristics.
      It was concluded that a higher degree of initial crystallinity was a major
      variable determining the earlier and more profound strength loss of PLLA than
      96L/4D PLA and 80L/20 D,L PLA. Samples with a higher initial iv were found to
      have a longer strength retention time than lower iv samples. Size-dependency was
      observed, as the strength retention time was shorter for the smaller diameter
      samples. This size-dependency was caused by faster iv decay. The amount of
      residual monomer content had a remarkable impact on strength retention. Neither
      the sample diameter, initial iv or residual monomer content were found to have an
      effect on the iv range in which there was a rapid decline in strength properties.
      Therefore, it was concluded that the inherent viscosity and/or molecular weight
      of oriented PLLA, 96L/4D PLA and 80L/20 D,L PLA is a major variable determining
      the strength retention of these materials. 

PMID- 24025530
TI  - Kibble-Zurek mechanism in a trapped ferromagnetic Bose-Einstein condensate.
AB  - Spontaneous spin vortex formation in a magnetic phase transition of a trapped
      spin-1 Bose-Einstein condensate is investigated based on mean-field theory. In a
      harmonic trapping potential, an inhomogeneous atomic density leads to spatial
      variations of the critical point, magnetization time, and spin correlation
      length. The Kibble-Zurek phenomena are shown to emerge even in such inhomogeneous
      spinor condensates, when the quench of the quadratic Zeeman energy is fast
      enough. For slow quench, the magnetized region gradually expands from the center
      of the trap, pushing out spin vortices, which hinders the Kibble-Zurek mechanism
      from occurring. The case of a toroidal trapping potential is also discussed. 

PMID- 24025529
TI  - Palliative hip surgery in severe cerebral palsy: a systematic review.
AB  - We performed a systematic review of the results of palliative hip surgery in
      severe cerebral palsy. Individuals with severe cerebral palsy frequently suffer
      from pain and other impairments because of dislocation or malformation of the
      hips. When preventive or reconstructive surgery fails, palliative intervention is
      performed. A number of salvage interventions have been described. We found
      articles on resection surgery of the femoral head, arthrodesis of the hip joint,
      and total hip replacement. The published literature does not clearly favor one
      procedure over the others. The resection arthroplasty technique developed by
      Castle is reported to yield the best results and fewer complications, and seems
      to eventually lead to a good outcome. 

PMID- 24025531
TI  - Osteoradionecrosis of the mandible: a case series at a single institution.
AB  - BACKGROUND: Osteoradionecrosis (ORN) defines exposed irradiated bone, which fails
      to heal over a period of 3-6 months without evidence of residual or recurrent
      tumor. In the previous decades, a staging and treatment protocol suggested by
      Marx, has dominated the approach to ORN. However, recently this paradigm is
      shifting. The purpose of this study was to evaluate our institutional experience
      in managing ORN through a retrospective review of case series from a large urban
      academic cancer centre. METHODS: A retrospective chart review was conducted to
      include all ORN cases from 2003 to 2009 diagnosed at the Department of
      Otolaryngology - Head and Neck Surgery and the Department of Dentistry. The
      staging of ORN was assessed as affected by tumor site, tumor stage, radiotherapy
      modality and dose, chemotherapy, dental work, and time to diagnosis. The
      effectiveness of hyperbaric oxygen therapy (HBO) and surgery in the management of
      ORN was evaluated. RESULTS: Fourteen cases of ORN were documented (incidence
      0.84%). Primary subsites included tonsils, tongue, retromolar trigone, parotid
      gland, soft palate and buccal mucosa. There were 5 (35.7%) stage 1, 3 (21.4%)
      stage 2, and 6 (42.9%) stage 3 cases. ORN severity was not significantly
      associated with gender, smoking, alcohol use, tumor site, T stage, N stage, AJCC
      stage, or treatment modality (radiation alone, surgery with adjuvant radiation or
      adjuvant chemoradiation). Patients treated with intensity-modulated radiotherapy
      developed less severe ORN compared to those treated with conventional
      radiotherapy (p < 0.015). ORN stage did not correlate with radiation dose. In one
      patient only dental procedures were performed following radiation and could be
      implicated as the cause of ORN. HBO therapy failed to prevent ORN progression.
      Surgical treatment was required for most stage 2 (partial resections and free
      tissue transfers) and stage 3 patients (mandibulectomies and free tissue
      transfers, including two flaps in one patient). At an average follow up of 26
      months, all patients were cancer-free, and there was no evidence of ORN in 84% of
      patients. CONCLUSIONS: In early ORN, we advocate a conservative approach with
      local care, while reserving radical resections with robust reconstruction with
      vascularized free tissue for advanced stages.

PMID- 24025533
TI  - Influence of post-treatment strategies on the properties of activated chars from
      broiler manure.
AB  - There are a myriad of carbonaceous precursors that can be used advantageously to
      produce activated carbons or chars, due to their low cost, availability and
      intrinsic properties. Because of the nature of the raw material, production of
      granular activated chars from broiler manure results in a significant ash
      fraction. This study was conducted to determine the influence of several pre- and
      post-treatment strategies in various physicochemical and adsorptive properties of
      the resulting activated chars. Pelletized samples of broiler litter and cake were
      pyrolyzed at 700  degrees C for 1h followed by a 45 min steam activation at 800 
      degrees C at different water flow rates from 1 to 5 mL min(-1). For each
      activation strategy, samples were either water-rinsed or acid-washed and rinsed
      or used as is (no acid wash/rinse). Activated char's physicochemical and
      adsorptive properties towards copper ions were selectively affected by both pre-
      and post-treatments. Percent ash reduction after either rinsing or acid washing
      ranged from 1.1 to 15.1% but washed activated chars were still alkaline with pH
      ranging from 8.4 to 9.1. Acid washing or water rinsing had no significant effect
      in the ability of the activated char to adsorb copper ions, however it
      significantly affected surface area, pH, ash content and carbon content. Instead,
      manure type (litter versus cake) and the activation water flow rate were
      determining factors in copper ion adsorption which ranged from 38 mg g(-1) to 104
      mg g(-1) of activated char. Moreover, strong positive correlations were found
      between copper uptake and concentration of certain elements in the activated char
      such as phosphorous, sulfur, calcium and sodium. Rinsing could suffice as a post
      treatment strategy for ash reduction since no significant differences in the
      carbon properties were observed between rinsed and acid wash treatments.

PMID- 24025532
TI  - Spatio-temporal profiling of Filamin A RNA-editing reveals ADAR preferences and
      high editing levels outside neuronal tissues.
AB  - RNA editing by ADARs can change the coding potential of protein-coding mRNAs. So
      far, this type of RNA editing has mainly been shown to affect RNAs expressed in
      the nervous system with much lower editing levels being observed in other
      tissues. The actin crosslinking proteins filamin alpha and filamin beta are
      widely expressed in most tissues. The mRNAs encoding either protein are edited at
      the same position leading to a conserved Q to R exchange in both proteins. Using
      bar-coded next generation sequencing, we show that editing of filamin alpha is
      most abundant in the gastrointestinal tract and only to a lesser extent in the
      nervous system. Using knockout mice, we show that ADARB1 (ADAR2) is responsible
      for the majority of FLNA editing, while ADAR1 can edit filamin alpha mRNA in some
      tissues quite efficiently. Interestingly, editing levels of filamin alpha and
      beta do not follow the same trend across tissues, suggesting a substrate-specific
      regulation of editing. 

PMID- 24025534
TI  - Trends of perfluorochemicals in Greenland ringed seals and polar bears:
      indications of shifts to decreasing trends.
AB  - Time-series of perfluorinated alkylated substances (PFASs) in East Greenland
      polar bears and East and West Greenland ringed seals were updated in order to
      deduce whether a response to the major reduction in perfluoroalkyl production in
      the early 2000s had occurred. Previous studies had documented an exponential
      increase of perfluorooctane sulphonate (PFOS) in liver tissue from both species.
      In the present study, PFOS was still the far most dominant compound constituting
      92% (West Greenland ringed seals), 88% (East Greenland ringed seals) and 85%
      (East Greenland polar bears). The PFOS concentrations increased up to 2006 with
      doubling times of approximately 6 years for the ringed seal populations and 14
      years in case of polar bears. Since then a rapid decrease has occurred with
      clearing half-lives of approximately 1, 2 and 4 years, respectively. In polar
      bears perfluorohexane sulphonate (PFHxS) and perfluorooctane sulphonamide (PFOSA)
      also showed decreasing trends in recent years as do perfluorodecanoic acid (PFDA)
      and perfluoroundecanoic acid (PFUnA). For the West Greenland ringed seal
      population perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), PFDA and
      PFUnA peaked in the mid 2000s, whereas PFNA, PFDA and PFUnA in the East Greenland
      population have been stable or increasing in recent years. The peak of PFASs in
      Greenland ringed seals and polar bears occurred at a later time than in Canadian
      seals and polar bears and considerably later than observed in seal species from
      more southern latitudes. We suggest that this could be explained by the distance
      to emission hot-spots and differences in long-range transport to the Arctic.

PMID- 24025535
TI  - Polybrominated diphenyl ethers occurrence in major inflowing rivers of Lake
      Chaohu (China): characteristics, potential sources and inputs to lake.
AB  - Eight commonly occurring polybrominated diphenyl ethers (PBDEs), including BDE
      28, 47, 99, 100, 153, 154, 183, 207, and 209, were investigated in water samples
      from seven major inflowing rivers of Lake Chaohu to determine the distribution
      characteristics, potential sources and inputs to the lake. The sum of 8 BDE
      congeners (Sigma8PBDEs) had a concentration varied from 0.31 to 84 ng L(-1), with
      those of BDE 209, BDE 47, BDE 99, and BDE 153 being 0.31-83, <0.012-0.36, <0.012
      1.3, and <0.012-0.77 ng L(-1), respectively. These levels were in the high range
      of the global PBDEs concentrations in the water environments. The highest
      concentrations of Sigma8PBDEs were detected in the western rivers, of which the
      main pollution sources were strongly related to human activities in urban
      centers, such as automobile-derived wastes. A sewage treatment plant was likely
      an important source of the lower brominated BDEs input to one western river. The
      correlation analyses (all p<0.05) between PBDEs and DOC, TN, TP, and EC,
      suggested that the distributions and sources of PBDEs in rivers might also be
      related with the soil erosion by heave floods. Sigma8PBDEs input to Lake Chaohu
      from the rivers outlets was estimated at 344 kg yr(-1) during the flood season.
      BDE 209 was the dominant contributor with an input of 340 kg yr(-1), followed by
      BDE 99 (1.3 kg yr(-1)), BDE 47 (0.83 kg yr(-1)) and BDE 153 (0.60 kg yr(-1)).

PMID- 24025536
TI  - Pharmaceuticals as emerging contaminants and their removal from water. A review.
AB  - The main objective of this study was to conduct an exhaustive review of the
      literature on the presence of pharmaceutical-derived compounds in water and on
      their removal. The most representative pharmaceutical families found in water
      were described and related water pollution issues were analyzed. The performances
      of different water treatment systems in the removal of pharmaceuticals were also
      summarized. The water treatment technologies were those based on conventional
      systems (chlorine, chlorine dioxide, wastewater treatment plants),
      adsorption/bioadsorption on activated carbon (from lotus stalks, olive-waste
      cake, coal, wood, plastic waste, cork powder waste, peach stones, coconut shell,
      rice husk), and advanced oxidation processes by means of ozonation (O3, O3/H2O2,
      O3/activated carbon, O3/biological treatment), photooxidation (UV, UV/H2O2,
      UV/K2S2O8, UV/TiO2, UV/H2O2/TiO2, UV/TiO2/activated carbon, photo-Fenton),
      radiolysis (e-Beam, 60Co, 137Cs. Additives used: H2O2, SO32-, HCO3-, CH3-OH, CO32
      , or NO3-), and electrochemical processes (Electrooxidation without and with
      active chlorine generation). The effect of these treatments on pharmaceutical
      compounds and the advantages and disadvantages of different methodologies used
      were described. The most important parameters of the above water treatment
      systems (experimental conditions, removal yield, pharmaceutical compound
      mineralization, TOC removal, toxicity evolution) were indicated. The key
      publications on pharmaceutical removal from water were summarized.

PMID- 24025537
TI  - Arsenoriboside degradation in marine systems: the use of bacteria culture
      incubation experiments as model systems.
AB  - Arsenoribosides (as glycerol; phosphate; sulfate and sulfonate) persisted in all
      bacteria-inoculated cultures irrespective of the source of bacteria (seawater,
      macro-algae surface) or the culture media used (DIFCO Marine Broth 2216 or novel
      blended Hormosira banksii tissue-based). This is unlike observations from
      traditional macro-algae tissue decomposition studies or in nature. In addition
      known arsenoriboside degradation products such as dimethylarsenoethanol (DMAE),
      dimethylarsenate (DMA), methylarsenate (MA) and arsenate - As(V) were not
      detected in any cultures. Consequently, the use of bacterial culture incubation
      experiments to explain the fate of arsenoribosides in marine systems appears
      limited as the processes governing arsenoriboside degradation in these
      experiments appear to be different to those in macro-algae tissue decomposition
      studies or in nature. 

PMID- 24025538
TI  - Personalizing therapy for colorectal cancer.
AB  - Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide.
      Several important scientific discoveries in the molecular biology of CRC have
      changed clinical practice in oncology. These included the comprehensive genome
      wide profiling of CRC by the Cancer Genome Atlas Network, the discovery of
      mutations along the RAS-RAF signaling pathway as major determinants of response
      to antibodies against the epidermal growth factor receptor, the elucidation of
      new molecular subsets of CRC or gene signatures that may predict clinical outcome
      after adjuvant chemotherapy, and the innovative targeting of the family of
      vascular endothelial growth factor and receptors. These new data have allowed
      oncologists to individualize drug therapy on the basis of a patient's tumor's
      unique molecular profile, especially in the management of metastatic CRC. This
      review article will discuss the progress of personalized medicine in the
      contemporary management of CRC. 

PMID- 24025539
TI  - Primary cervical osteomyelitis.
AB  - BACKGROUND: Cervical osteomyelitis accounts for only 3-11% of all cases of spinal
      osteomyelitis, and the diagnosis may be delayed. The characteristics of different
      pathogens causing cervical osteomyelitis are not fully understood, and there are
      few established guidelines for treatment. METHODS: The cases of six patients who
      presented with primary cervical osteomyelitis in the orthopedic department
      between January 2002 and March 2012 were retrospectively reviewed. All patients
      had been treated with anterior decompression, instrumentation, and autograft
      fusion. Data about preoperative and postoperative symptoms, neurological
      function, pain, C-reactive protein (CRP) levels, and the results of plain film
      and magnetic resonance imaging were reviewed. RESULTS: Intraoperative cultures
      revealed Staphylococcus aureus in three patients, Propionibacterium acnes in two,
      and Mycobacterium tuberculosis in one. The mean duration between symptoms and
      diagnosis was 7.2 weeks (range, 3-12 weeks). Three patients with S. aureus
      infections had relatively higher preoperative CRP levels (mean, 173 mg/L) than
      did the patients with P. acnes infections or tuberculosis (mean, 5.5 mg/L).
      However, bony destruction was less severe in patients with S. aureus infections
      than in those patients with P. acnes and tuberculosis. All CRP levels returned to
      normal in 12 weeks, and all six patients had a final stable cervical alignment
      and fusion. Ultimately, neurological function and pain score improved in all
      patients. CONCLUSION: Cervical osteomyelitis caused by S. aureus has an acute
      onset, higher CRP level, shorter duration from onset to diagnosis and thus causes
      less bony destruction. By contrast, cervical osteomyelitis caused by P. acnes and
      tuberculosis has an indolent course, a low or even normal CRP level, a longer
      duration from onset to diagnosis, and produces more severe bony destruction.
      Anterior decompression, instrumentation, and autograft fusion can be successfully
      used to treat primary cervical osteomyelitis. However, a mesh cage can also be a
      good alternative to an autograft.

PMID- 24025541
TI  - The emergence of non-secretory multiple myeloma during the non-cytotoxic
      treatment of essential thrombocythemia: a case report.
AB  - INTRODUCTION: The emergence of multiple myeloma as a second malignancy in
      patients with essential thrombocythemia is extremely rare. Several cases have
      been published so far, pointing out the impact of a cytotoxic effect during
      treatment of essential thrombocythemia on the development of multiple myeloma.
      CASE PRESENTATION: We report the case of a 52-year-old Caucasian man who
      presented to our hospital because of leukocytosis, a slightly decreased
      hemoglobin level and thrombocytosis. After a complete hematological work-up,
      essential thrombocythemia was diagnosed. The patient was included in a
      multicenter clinical study, treated with anagrelide and his platelet counts were
      maintained in the normal range for more than 3 years. A sudden drop in his
      hemoglobin level with normal leukocyte and platelet count occurred at the same
      time as a back pain. Magnetic resonance imaging of his spine revealed the
      existence of a pathological fracture of Th4, the collapse of the upper edge of
      Th7 and osteolytic lesions of multiple thoracic vertebrae. Repeated hematological
      examinations, including bone biopsy with immunohistochemistry, disclosed
      diagnosis of multiple myeloma of the non-secretory type. CONCLUSIONS: To the best
      of our knowledge this is the first published case in which multiple myeloma
      developed during the treatment of essential thrombocythemia with the non
      cytotoxic drug anagrelide. Our attempts to find a common origin for the
      coexistence of multiple myeloma and essential thrombocythemia have not confirmed
      the genetic basis of their appearance. Further studies are needed to determine
      the biological impact of this coexistence.

PMID- 24025540
TI  - Team-based learning for psychiatry residents: a mixed methods study.
AB  - BACKGROUND: Team-based learning (TBL) is an effective teaching method for medical
      students. It improves knowledge acquisition and has benefits regarding learner
      engagement and teamwork skills. In medical education it is predominately used
      with undergraduates but has potential benefits for training clinicians. The aims
      of this study were to examine the impact of TBL in a sample of psychiatrists in
      terms of classroom engagement, attitudes towards teamwork, learner views and
      experiences of TBL. METHODS: Forty-four psychiatry residents participated in an
      Addictions Psychiatry TBL module. Mixed-methods were used for evaluation. Self
      rated measures of classroom engagement (Classroom Engagement Survey, CES) were
      compared with conventional lectures, and attitudes regarding the value of teams
      (Value of Teams Scale, VTS) were compared before and after the module.
      Independent t-tests were used to compare 'lecture' CES scores with TBL CES scores
      and pre and post scores for the VTS. Feedback questionnaires were completed.
      Interviews were conducted with a subset of residents and transcripts analysed
      using thematic analysis. RESULTS: Twenty-eight residents completed post-course
      measures (response rate 63.6%). Seven participants volunteered for qualitative
      interviews-one from each team. There was a significant difference in the mean CES
      score lectures compared to TBL (p < 0.001) but no difference was found in mean
      VTS score pre and post for either subscale (p = 0.519; p = 0.809). All items on
      the feedback questionnaire were positively rated except two regarding session
      preparation. The qualitative analysis generated seven themes under four domains:
      'Learning in teams', 'Impact on the individual learner', 'Relationship with the
      teacher' and 'Efficiency and effectiveness of the learning process'. CONCLUSIONS:
      In this group of residents, TBL significantly improved learner-rated classroom
      engagement and seemed to promote interactivity between learners. TBL was
      generally well-received, although required learners to prepare for class which
      was difficult for some. TBL did not change these clinicians' views about
      teamwork.

PMID- 24025542
TI  - Structure, morphology, and photoluminescence of porous Si nanowires: effect of
      different chemical treatments.
AB  - The structure and light-emitting properties of Si nanowires (SiNWs) fabricated by
      a single-step metal-assisted chemical etching (MACE) process on highly boron
      doped Si were investigated after different chemical treatments. The Si nanowires
      that result from the etching of a highly doped p-type Si wafer by MACE are fully
      porous, and as a result, they show intense photoluminescence (PL) at room
      temperature, the characteristics of which depend on the surface passivation of
      the Si nanocrystals composing the nanowires. SiNWs with a hydrogen-terminated
      nanostructured surface resulting from a chemical treatment with a hydrofluoric
      acid (HF) solution show red PL, the maximum of which is blueshifted when the
      samples are further chemically oxidized in a piranha solution. This blueshift of
      PL is attributed to localized states at the Si/SiO2 interface at the shell of Si
      nanocrystals composing the porous SiNWs, which induce an important pinning of the
      electronic bandgap of the Si material and are involved in the recombination
      mechanism. After a sequence of HF/piranha/HF treatment, the SiNWs are almost
      fully dissolved in the chemical solution, which is indicative of their fully
      porous structure, verified also by transmission electron microscopy
      investigations. It was also found that a continuous porous Si layer is formed
      underneath the SiNWs during the MACE process, the thickness of which increases
      with the increase of etching time. This supports the idea that porous Si
      formation precedes nanowire formation. The origin of this effect is the increased
      etching rate at sites with high dopant concentration in the highly doped Si
      material. 

PMID- 24025543
TI  - ATP-binding cassette transporter A1 in lipoprotein metabolism and
      atherosclerosis: a new piece of the complex puzzle.

PMID- 24025544
TI  - Myocardin: new therapeutic agent in vascular disease?

PMID- 24025545
TI  - Blockade of cytidine triphosphate synthase regulates smooth muscle cell and
      endothelial cell proliferation differentially.

PMID- 24025547
TI  - Age at dieting onset, body mass index, and dieting practices. A twin study.
AB  - OBJECTIVE: Using a twin study design, we sought to determine whether an early age
      at dieting onset is a risk factor for higher adult body mass index (BMI) or use
      of risky dieting practices, independent of genetic and familial factors. METHOD:
      Female twins ages 18-60 years (N=950) from the University of Washington Twin
      Registry completed 2 surveys an average of 3 years apart. Analyses of individual
      twins and within-twin pairs tested associations of self-reported age at dieting
      onset with (1) adult BMI at baseline, (2) change in BMI between the two surveys
      and (3) risky dieting behaviors at baseline. RESULTS: In analyses mimicking
      studies of unrelated individuals, an earlier age at dieting onset was associated
      with greater adult BMI (p=0.003), higher Restraint Scale scores (p<0.001),
      greater use of risky dieting behaviors (p=0.04) and more weight cycling episodes
      (p<0.001). In within-pair models that control for genetic and familial factors,
      the only significant association was between an earlier age at dieting onset and
      more weight cycling episodes (p=0.006). DISCUSSION: Underlying genetic and
      familial factors may influence associations of early dieting with higher adult
      BMIs and risky dieting practices in women.

PMID- 24025549
TI  - Quantitative x-ray radiography using grating interferometry: a feasibility study.
AB  - X-ray grating interferometry is a promising tool for medical imaging because of
      its capability of providing additional and complementary information to
      conventional absorption-based methods. This technology can simultaneously measure
      absorption, differential phase and small-angle scattering signals from the
      sample, significantly improving the diagnostic content. In this work, we present
      a method which uses the image (dubbed the R image) obtained by taking the ratio
      of the absorption and small-angle scattering signals to gain quantitative insight
      from a radiographic x-ray projection. We demonstrate that with the help of the R
      image we can successfully distinguish among different (light-Z) plastic
      materials, which are usually used to mimic soft tissues. Two potential
      applications in medical imaging, such as quantitative x-ray radiography and
      volumetric breast density estimation, are demonstrated. 

PMID- 24025548
TI  - The effects of food-related attentional bias training on appetite and food
      intake.
AB  - Obese and overweight individuals show a marked attentional bias to food cues.
      Food-related attentional bias may therefore play a causal role in over-eating. To
      test this possibility, the current study experimentally manipulated attentional
      bias towards food using a modified version of the visual probe task in which cake
      stationery item image pairs were presented for 500 ms each. Participants (N=60)
      were either trained to attend to images of cake, trained to avoid images of cake,
      or assigned to a no-training control group. Hunger was measured before and after
      the training. Post-training, participants were given the opportunity to consume
      cake as well as a non-target food (crisps) that was not included in the training.
      There was weak evidence of an increase in attentional bias towards cake in the
      attend group only. We found no selective effects of the training on hunger or
      food intake, and little evidence for any gender differences. Our study suggests
      that attentional bias for food is particularly ingrained and difficult to modify.
      It also represents a first step towards elucidating the potential functional
      significance of food-related attentional biases and the lack of behavioural
      effects is broadly consistent with single-session attentional training studies
      from the addiction literature. An alternative hypothesis, that attentional bias
      represents a noncausal proxy for the motivational impact of appetitive stimuli,
      is considered.

PMID- 24025550
TI  - BPAG1-e restricts keratinocyte migration through control of adhesion stability.
AB  - Bullous pemphigoid antigen 1 (BPAG1-e, also known as BP230) is a member of the
      plakin family of hemidesmosome cytoskeletal linker proteins that is encoded by an
      isoform of the dystonin (DST) gene. Recently, we reported two unrelated families
      with homozygous nonsense mutations in this DST isoform that led to
      ultrastructural loss of hemidesmosomal inner plaques and clinical features of
      trauma-induced skin fragility. We now demonstrate that keratinocytes isolated
      from these individuals have significant defects in adhesion, as well as increased
      cell spreading and migration. These mutant keratinocytes also display reduced
      levels of beta4 integrins at the cell surface but increased total protein levels
      of keratin-14 and beta1 integrins. These alterations in cell behavior and protein
      expression were not seen in control keratinocytes in which BPAG1-e expression had
      been silenced by stable expression of short hairpin RNA to target DST. The
      failure of knockdown approaches to recapitulate the changes in morphology,
      adhesion, and migration seen in patient cells therefore suggests such approaches
      are not appropriate to study loss of this protein in vivo. The contrasting
      findings in keratinocytes harboring naturally occurring mutations, however,
      demonstrate a previously unappreciated key role for BPAG1-e in regulating
      keratinocyte adhesion and migration and suggest a requirement for this protein in
      controlling functional switching between integrin types in epithelial cells. 

PMID- 24025551
TI  - Oral administration of poly-gamma-glutamate ameliorates atopic dermatitis in
      Nc/Nga mice by suppressing Th2-biased immune response and production of IL-17A.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease that is closely
      related to dysregulation of the T helper type 1 and 2 (Th1)/Th2 balance. A
      previous study showed that high molecular mass poly-gamma-glutamate (gamma-PGA)
      isolated from Bacillus subtilis sp. Chungkookjang induces the production of IL-12
      from dendritic cells (DCs). Here, we investigated the effect of gamma-PGA on AD
      like skin disease using an Nc/Nga mouse model. In vitro, gamma-PGA activated DCs
      and induced IL-12 production in mice. In vivo, oral administration of gamma-PGA
      markedly reduced the AD symptoms, similar to the response seen in the
      dexamethasone (Dex)-treated group. Treatment with gamma-PGA also decreased the
      serum levels of IgG1, the skin levels of Th2 cytokines, the extent of skin
      inflammation, and the accumulation of mast cells. Furthermore, gamma-PGA was
      effective against established AD, significantly decreasing serum IgE and Th2
      cytokines in the inflamed tissue. Interestingly, the production of IL-17A in
      splenocytes was also suppressed by gamma-PGA, indicating that it inhibits both
      Th2 and Th17 immune responses. Collectively, these results suggest that oral
      administration of gamma-PGA could be a therapeutic strategy for treating AD via
      the modulation of Th2-biased immune responses in an Nc/Nga mouse model. 

PMID- 24025552
TI  - Human basal cell carcinoma tumor-initiating cells are resistant to etoposide.

PMID- 24025553
TI  - Is a single BRAF wild-type test sufficient to exclude melanoma patients from
      vemurafenib therapy?

PMID- 24025554
TI  - Five years of designing wireless sensor networks in the Donana Biological Reserve
      (Spain): an applications approach.
AB  - Wireless Sensor Networks (WSNs) are a technology that is becoming very popular
      for many applications, and environmental monitoring is one of its most important
      application areas. This technology solves the lack of flexibility of wired sensor
      installations and, at the same time, reduces the deployment costs. To demonstrate
      the advantages of WSN technology, for the last five years we have been deploying
      some prototypes in the Donana Biological Reserve, which is an important protected
      area in Southern Spain. These prototypes not only evaluate the technology, but
      also solve some of the monitoring problems that have been raised by biologists
      working in Donana. This paper presents a review of the work that has been
      developed during these five years. Here, we demonstrate the enormous potential of
      using machine learning in wireless sensor networks for environmental and animal
      monitoring because this approach increases the amount of useful information and
      reduces the effort that is required by biologists in an environmental monitoring
      task. 

PMID- 24025556
TI  - Finger vein recognition based on personalized weight maps.
AB  - Finger vein recognition is a promising biometric recognition technology, which
      verifies identities via the vein patterns in the fingers. Binary pattern based
      methods were thoroughly studied in order to cope with the difficulties of
      extracting the blood vessel network. However, current binary pattern based finger
      vein matching methods treat every bit of feature codes derived from different
      image of various individuals as equally important and assign the same weight
      value to them. In this paper, we propose a finger vein recognition method based
      on personalized weight maps (PWMs). The different bits have different weight
      values according to their stabilities in a certain number of training samples
      from an individual. Firstly we present the concept of PWM, and then propose the
      finger vein recognition framework, which mainly consists of preprocessing,
      feature extraction, and matching. Finally, we design extensive experiments to
      evaluate the effectiveness of our proposal. Experimental results show that PWM
      achieves not only better performance, but also high robustness and reliability.
      In addition, PWM can be used as a general framework for binary pattern based
      recognition. 

PMID- 24025555
TI  - Strontium-doped hematite as a possible humidity sensing material for soil water
      content determination.
AB  - The aim of this work is to study the sensing behavior of Sr-doped hematite for
      soil water content measurement. The material was prepared by solid state reaction
      from commercial hematite and strontium carbonate heat treated at 900  degrees C.
      X-Ray diffraction, scanning electron microscopy and mercury intrusion porosimetry
      were used for microstructural characterization of the synthesized powder. Sensors
      were then prepared by uniaxially pressing and by screen-printing, on an alumina
      substrate, the prepared powder and subsequent firing in the 800-1,000  degrees C
      range. These sensors were first tested in a laboratory apparatus under humid air
      and then in an homogenized soil and finally in field. The results evidenced that
      the screen printed film was able to give a response for a soil matric potential
      from about 570 kPa, that is to say well below the wilting point in the used soil.

PMID- 24025557
TI  - Improving pyroelectric energy harvesting using a sandblast etching technique.
AB  - Large amounts of low-grade heat are emitted by various industries and exhausted
      into the environment. This heat energy can be used as a free source for
      pyroelectric power generation. A three-dimensional pattern helps to improve the
      temperature variation rates in pyroelectric elements by means of lateral
      temperature gradients induced on the sidewalls of the responsive elements. A
      novel method using sandblast etching is successfully applied in fabricating the
      complex pattern of a vortex-like electrode. Both experiment and simulation show
      that the proposed design of the vortex-like electrode improved the electrical
      output of the pyroelectric cells and enhanced the efficiency of pyroelectric
      harvesting converters. A three-dimensional finite element model is generated by
      commercial software for solving the transient temperature fields and exploring
      the temperature variation rate in the PZT pyroelectric cells with various
      designs. The vortex-like type has a larger temperature variation rate than the
      fully covered type, by about 53.9%.The measured electrical output of the vortex
      like electrode exhibits an obvious increase in the generated charge and the
      measured current, as compared to the fully covered electrode, by of about 47.1%
      and 53.1%, respectively. 

PMID- 24025558
TI  - Sensors in agriculture and forestry.

PMID- 24025559
TI  - An experimental study on fabricating an inverted mesa-type quartz crystal
      resonator using a cheap wet etching process.
AB  - In this study, a miniaturized high fundamental frequency quartz crystal
      microbalance (QCM) is fabricated for sensor applications using a wet etching
      technique. The vibration area is reduced in the fabrication of the high frequency
      QCM with an inverted mesa structure. To reduce the complexity of the side wall
      profile that results from anisotropic quartz etching, a rectangular vibration
      area is used instead of the conventional circular structure. QCMs with high Q
      values exceeding 25,000 at 47 MHz, 27,000 at 60 MHz, 24,000 at 73 MHz and 25,000
      at 84 MHz are fabricated on 4 * 4 mm2 chips with small vibration areas of 1.2 *
      1.4 mm2. A PMMA-based flow cell is designed and manufactured to characterize the
      behavior of the fabricated QCM chip in a liquid. Q values as high as 1,006 at 47
      MHz, 904 at 62 MHz, 867 at 71 MHz and 747 at 84 MHz are obtained when one side of
      the chip is exposed to pure water. These results show that fabricated QCM chips
      can be used for bio- and chemical sensor applications in liquids. 

PMID- 24025560
TI  - BPR0C305, an orally active microtubule-disrupting anticancer agent.
AB  - BPR0C305 is a novel N-substituted indolyl glyoxylamide previously reported with
      in-vitro cytotoxic activity against a panel of human cancer cells including P-gp
      expressing multiple drug-resistant cell sublines. The present study further
      examined the underlying molecular mechanism of anticancer action and evaluated
      the in-vivo antitumor activities of BPR0C305. BPR0C305 is a novel synthetic small
      indole derivative that demonstrates in-vitro activities against human cancer cell
      growth by inhibiting tubulin polymerization, disrupting cellular microtubule
      assembly, and causing cell cycle arrest at the G2/M phase. It is also orally
      active against leukemia and solid tumor growths in mouse models. Findings of
      these pharmacological and pharmacokinetic studies suggest that BPR0C305 is a
      promising lead compound for further preclinical developments.

PMID- 24025562
TI  - Current strategies to minimize toxicity of oxaliplatin: selection of
      pharmacogenomic panel tests.
AB  - Oxaliplatin is an anticancer drug routinely used to treat colorectal,
      gastroesophageal, ovarian, breast, head/neck, and genitourinary cancers.
      Discontinuation of oxaliplatin treatment is mostly because of peripheral
      neuropathy, more often than for tumor progression, potentially compromising
      patient benefit. Several strategies to prevent neurotoxicity have so far been
      investigated. To overcome this life-threatening side effect, while taking
      advantage of the antineoplastic activities of oxaliplatin, we describe in detail
      recent findings on the underlying mechanisms of genetic variants associated with
      toxicity and resistance to oxaliplatin-based chemotherapy in colorectal cancer. A
      comprehensive panel of eight polymorphisms, previously validated as significant
      markers related to oxaliplatin toxicity, is proposed and discussed. In addition,
      the most common available strategies or methods to prevent/minimize the toxicity
      were described in detail. Moreover, an early outline evaluation of the genotyping
      costs and methods was taken in consideration. With the availability of individual
      pharmacogenomic profiles, the oncologists will have new means to make treatment
      decisions for their patients that maximize benefit and minimize toxicity. With
      this purpose in mind, the clinician and lab manager should cooperate to evaluate
      the advantages and limitations, in terms of costs and applicability, of the most
      appropriate pharmacogenomic tests for routine incorporation into clinical
      practice.

PMID- 24025561
TI  - Isolation and chemopreventive evaluation of novel naphthoquinone compounds from
      Alkanna tinctoria.
AB  - Botanically derived natural products have recently become an attractive source of
      new chemotherapeutic agents. To explore active anticolorectal cancer compounds,
      we carried out phytochemical studies on Alkanna tinctoria and isolated eight
      quinone compounds. Using different spectral methods, compounds were identified as
      alkannin (1), acetylalkannin (2), angelylalkannin (3), 5-methoxyangenylalkannin
      (4), dimethylacryl alkannin (5), arnebifuranone (6), alkanfuranol (7), and
      alkandiol (8). Compounds 4, 7, and 8 are novel compounds. The structures of the
      three novel compounds were elucidated on the basis of extensive spectroscopic
      evidence including high-resolution mass spectrometry and nuclear magnetic
      resonance spectra. The antiproliferative effects of these eight compounds on HCT
      116 and SW-480 human colorectal cancer cells were determined using the MTS
      method. Cell cycle and apoptosis were determined using flow cytometry. Enzymatic
      activities of caspases were determined using a colorimetric assay, and
      interactions of compound 4 and caspase 9 were explored by docking analysis. Among
      the eight compounds, alkannin (1), angelylalkannin (3), and 5
      methoxyangenylalkannin (4) showed strong antiproliferative effects, whereas
      compound 4 showed the most potent effects. Compound 4 arrested cancer cells in
      the S and G2/M phases, and significantly induced cell apoptosis. The apoptotic
      effects of compound 4 were supported by caspase assay and docking analysis. The
      structural-functional relationship assay suggested that to increase anticancer
      potential, future modifications on alkannin (1) should focus on the hydroxyl
      groups at C-5 and C-8.

PMID- 24025563
TI  - ERCC1 expression levels predict the outcome of platinum-based chemotherapies in
      advanced bladder cancer: a meta-analysis.
AB  - The objective of this study was to provide a precise evaluation of whether
      expression levels of excision repair cross-complementation group 1 (ERCC1) are
      associated with objective response, overall survival (OS), and median survival in
      patients with advanced bladder cancer treated with platinum-based chemotherapy.
      Systematic computerized searches of the electronic databases PubMed, EMBASE,
      Ovid, ASCO, and CNKI were performed and a meta-analysis was carried out to
      evaluate the correlation between ERCC1 expression levels and objective response
      rate, OS, or progression-free survival in patients with advanced bladder cancer
      receiving platinum-based chemotherapy. References within the articles identified
      were also searched manually. STATA package version 11.0 was used for the
      comprehensive quantitative analyses. A total of six studies involving 356
      patients, of which ERCC1 expression was high/positive in 138 (38.8%) and
      low/negative in 218 (61.2%), were included in the meta-analysis. The median age
      of the patients was 63.7 years. The objective response rate favored patients with
      ERCC1 low/negative expression after platinum-based chemotherapy, but showed no
      significant difference [odds ratio 0.86, 95% confidence interval (CI) 0.36-2.06,
      P=0.734]. The median OS time and the median progression-free survival time were
      significantly prolonged when ERCC1 low/negative expression was compared with
      ERCC1 high/positive expression (hazard ratio 0.69, 95% CI 0.54-0.89, P=0.004, and
      hazard ratio 0.76, 95% CI 0.66-0.89, P=0.000, respectively). In conclusion,
      low/negative expression of ERCC1 was associated with higher objective response,
      median progression-free survival, and median OS in patients with advanced bladder
      cancer treated with platinum-based chemotherapy. ERCC1 may be a suitable marker
      of prognosis and sensitivity to platinum-based chemotherapy in patients with
      advanced bladder cancer. Larger studies and further clinical trials are warranted
      to confirm these findings. 

PMID- 24025565
TI  - Colorectal cancer patient on maintenance dialysis successfully treated with
      cetuximab.
AB  - The number of patients affected by cancer on maintenance hemodialysis has been
      increasing. Only few data on the cytotoxic drugs management are reported in the
      literature. Chemotherapy schedules commonly used in colorectal cancer necessitate
      dose adjustment and appropriate timing relative to the hemodialysis session.
      Here, we report a case of a 66-year-old male patient under hemodialysis and
      affected by metastatic colorectal cancer, unsuitable for standard chemotherapy.
      He received cetuximab monotherapy at a dose of 400 mg/m for the first dose, and
      then 250 mg/m weekly after hemodialysis and 3 days before his next run of
      dialysis. After 3 months of treatment, computed tomography scan showed a partial
      response of disease and the patient experienced a clinical benefit, without
      significant toxicities. We confirmed the feasibility and efficacy, with
      acceptable toxicity, of a standard schedule of cetuximab in patients under
      hemodialysis. 

PMID- 24025564
TI  - Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD, a
      collagen-targeted parathyroid hormone analog, in a non-depilated mouse model.
AB  - Alopecia is a psychologically devastating complication of chemotherapy for which
      there is currently no effective therapy. PTH-CBD is a collagen-targeted
      parathyroid hormone analog that has shown promise as a therapy for alopecia
      disorders. This study compared the efficacy of prophylactic versus therapeutic
      administration of PTH-CBD in chemotherapy-induced alopecia using a mouse model
      that mimics the cyclic chemotherapy dosing used clinically. C57BL/6J mice were
      treated with a single subcutaneous injection of PTH-CBD (320 mcg/kg) or vehicle
      control before or after hair loss developing from three courses of
      cyclophosphamide chemotherapy (50-150 mg/kg/week). Mice receiving chemotherapy
      alone developed hair loss and depigmentation over 6-12 months. Mice pretreated
      with PTH-CBD did not develop these changes and maintained a normal-appearing
      coat. Mice treated with PTH-CBD after development of hair loss showed a partial
      recovery. Observations of hair loss were confirmed quantitatively by gray scale
      analysis. Histological examination showed that in mice receiving chemotherapy
      alone, there were small, dystrophic hair follicles mostly in the catagen phase.
      Mice receiving PTH-CBD before chemotherapy showed a mix of normal-appearing
      telogen and anagen hair follicles with no evidence of dystrophy. Mice receiving
      PTH-CBD therapy after chemotherapy showed intermediate histological features. PTH
      CBD was effective in both the prevention and the treatment of chemotherapy
      induced alopecia in mice, but pretreatment appears to result in a better cosmetic
      outcome. PTH-CBD shows promise as an agent in the prevention of this complication
      of chemotherapy and improving the quality of life for cancer patients. 

PMID- 24025566
TI  - On the importance of food.

PMID- 24025567
TI  - Fasting of mice: a review.
AB  - Fasting of mice is a common procedure performed in association with many
      different types of experiments mainly in order to reduce variability in
      investigatory parameters or to facilitate surgical procedures. However, the
      effects of fasting not directly related to the investigatory parameters are often
      ignored. The aim of this review is to present and summarize knowledge about the
      effects of fasting of mice to facilitate optimization of the fasting procedure
      for any given study and thereby maximize the scientific outcome and minimize the
      discomfort for the mice and hence ensure high animal welfare. The results are
      presented from a number of experimental studies, providing evidence for fasting
      induced changes in hormone balance, body weight, metabolism, hepatic enzymes,
      cardiovascular parameters, body temperature and toxicological responses. A
      description of relevant normal behaviour and standard physiological parameters is
      given, concluding that mice are primarily nocturnal and consume two-thirds of
      their total food intake during the night. It is argued that overnight fasting of
      mice is not comparable with overnight fasting of humans because the mouse has a
      nocturnal circadian rhythm and a higher metabolic rate. It is suggested that
      because many physiological parameters are regulated by circadian rhythms, fasting
      initiated at different points in the circadian rhythm has different impacts and
      produces different results. 

PMID- 24025568
TI  - Considerations to maximize fat mass gain in a mouse model of diet-induced weight
      gain.
AB  - Mouse experimental models of diet-induced weight gain are commonly used as
      analogs to human obesity; however, a wide variety of feeding methods have been
      used and the most effective way to maximize weight gain is not known. Maximizing
      weight gain may allow for a reduction in the number of animals required for a
      given experiment. The purpose of this study was how to cause the greatest amount
      of weight gain in CD-1 mice by modifying the composition and source of their
      diet. To accomplish this goal, we completed two experiments: (1) Effect of
      dietary macronutrient fat intake (60% (HF60), 45% (HF45), 30% (HF30), or 13.5%
      (CON) fat diet for 18 weeks); and (2) Effect of 1:1 mixed HF60 and CON diets.
      Outcome measures included food intake, body mass, and body composition, which
      were measured bi-weekly and statistically analyzed using a repeated measures
      analysis of variance (RM-ANOVA). In Experiment 1, the greatest increase in body
      and fat mass was observed in HF60 (36%) and HF45 (29%) compared with HF30 and CON
      (P < 0.05). In Experiment 2, HF + stock diet (SK) gained 25% more body mass and
      70% more fat mass than HF (P < 0.05). Collectively, these findings suggest that
      using a high-fat based diet (>45% calories from fat), mixed with a stock diet,
      results in substantially more weight gain over a similar period, of time, which
      would allow an investigator to use ~40% fewer animals in their experimental
      model.

PMID- 24025569
TI  - Tip-enhanced Raman spectroscopy of lipid bilayers in water with an alumina- and
      silver-coated tungsten tip.
AB  - Tip-enhanced Raman spectroscopy (TERS) of supported phospholipid bilayers in an
      aqueous environment is discussed in this paper. Two bilayer membranes were
      examined: 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC). We fabricated alumina- and silver-coated
      tungsten tips that are very robust in water. There was a large time-dependence in
      the TERS spectra for the DOPC bilayers, whereas no such time-dependence was
      observed in the DPPC bilayer spectra under the probe tip. The spectral changes of
      DOPC bilayers are discussed in terms of the fluidity of the liquid crystalline
      phase. Time-resolved TERS thus has the potential to characterize inhomogeneity
      and diffusion in fluidic phospholipid bilayer membranes. 

PMID- 24025570
TI  - Protein-based open sandwich immuno-PCR for sensitive detection of small
      biomarkers.
AB  - Open sandwich (OS) immunoassay utilizes antigen-dependent stabilization of an
      antibody variable region to quantify various antigens, enabling noncompetitive
      detection of small molecules with a broad working range. For further improvement
      of its sensitivity, OS Immuno-PCR was attempted with recombinant fusion proteins.
      The maltose binding protein-fused heavy chain variable region (MBP-V(H)) of an
      antibody that recognizes the C-terminal fragment of human osteocalcin (bone Gla
      protein, BGP), a biomarker for bone-related diseases, was immobilized onto
      microplate wells, and the antigen together with streptavidin (SA)-fused light
      chain variable region of the same antibody (SA-V(L)) was added and incubated. The
      amount of immobilized SA-V(L) was quantified by tethered biotinylated DNA, which
      was used to estimate the amount of antigen by realtime PCR. When BGP C-terminal
      peptide was detected, the limit of detection was 100 fg/mL, which was superior
      than that of our previously reported phage-based OS Immuno-PCR. The developed OS
      Immuno-PCR system will be useful for the detection of small molecule biomarkers
      for disease prevention.

PMID- 24025571
TI  - Highly sensitive and rapid assay of substance P and streptolysin O in human serum
      using immuno-liposomes and gramicidin channels.
AB  - A highly sensitive and rapid method for the determination of substance P (SP) and
      streptolysin O (SLO) in human serum is described. The assay is based on enriching
      the analyte by agglutination/precipitation of immuno-liposomes and enhancing the
      fluorescence intensity by gramicidin A channels. A mixture of the immuno
      liposomes encapsulating a pH-sensitive fluorescence dye BCECF, gramicidin A and a
      given concentration of SP (or SLO) is preincubated in a solution and captured on
      anti-SP (or anti-SLO)-modified cover slips, followed by measuring fluorescence
      images after removing excess liposomes. The method allowed quantifying SP and SLO
      in the range from sub-pg mL(-1) to pg mL(-1), with detection limits of 0.32 pg
      mL(-1) and 8 fg mL(-1), respectively. The present method could determine SP and
      SLO in 50-125 times diluted human serum without any extraction steps. The assay
      can be completed within 60 min.

PMID- 24025573
TI  - Ofloxacin determination in urine, serum and pharmaceuticals using an automatic
      flow potentiometric system.
AB  - An automatic system was developed to determine ofloxacin in biological fluids and
      pharmaceutical formulations. Drug detection was carried out by a potentiometric
      membrane sensor based on [bis(trifluoromethyl)phenyl]borate as molecular
      recognition material. The tubular shaped detector system was solidly attached to
      the manifold, creating a high-throughput stable setup (50 samples per hour)
      appropriate for routine antibiotic assessment. Under the optimized flow
      conditions, the sensor displayed a mean detection limit of 1 * 10(-5) M, a linear
      response over the concentrations of 2 * 10(-5) to 5 * 10(-3) M (slope of 57.4 mV
      decade(-1)) and a wide working pH range (2.1 - 6.6). The procedure was
      successfully applied to ofloxacin analysis in pharmaceuticals (relative deviation
      lower than 6%) and biological fluids at levels usually found after drug
      administration of clinical doses (recoveries between 91 and 106%). No significant
      interference from common excipients found in commercial formulations and
      inorganic ions usually present in biological fluids was noticed. 

PMID- 24025572
TI  - Biophysical analysis of astrocytes apoptosis triggered by larval E/S antigen from
      cerebral toxocarosis-causing pathogen Toxocara canis.
AB  - Toxocarosis is a zoonosis caused by the transmission of the Toxocara canis (T.
      canis) larvae to humans. Its infectious third-stage larvae can invade the brains
      of paratenic hosts. The resultant brain damage can result in cerebral toxocarosis
      (CT). Astrocytes have important neurotrophic and neuroprotective functions in the
      brain. Substantial studies have shown that astrocyte apoptosis may contribute to
      the pathogenesis of many acute and chronic neurodegenerative disorders. We
      propose an alternation detection method, a combination of the astigmatic
      detection microscopy (ADM) and atomic force microscopy (AFM) techniques, to
      investigate the apoptosis of astrocytes triggered with T. canis larval
      excretory/secretory (Tc E/S) antigen. The variation in the pathology of a cell's
      morphological changes was investigated with ADM and AFM analyses and then
      confirmed by western blotting. The results showed that the round cells increased
      as the concentration of Tc E/S antigen and incubated time increased. In addition,
      the mean height of apoptotic cells was approximately twice that of untreated
      normal cells, which meant there was correlation between the Tc E/S antigen
      treatment and cell height. For each cleaved caspase-3 in the cells cocultured
      with Tc E/S antigen and incubated for 9 h, the corresponding intensities
      increased about 34-fold (34.4 +/- 1.8) compared with those of the control cells.
      This method can provide researchers with a perspective for understanding the
      limited information on the mechanism of astroglial injury and death during a T.
      canis larval invasion in a brain infection. 

PMID- 24025574
TI  - A fluorescent chemosensor for Hg2+ based on a rhodamine derivative in an aqueous
      solution.
AB  - In this paper, we unveil a novel rhodamine compound-based fluorescent chemosensor
      (compound 1) for fluorescent detection of Hg(2+) in an aqueous solution. The
      fluorescence enhancement of compound 1 was attributed to the formation of a
      complex between compound 1 and Hg(2+) by 1:1 complex ration (K = 8.0 * 10(4)),
      which has been utilized as the basis of fabrication of the Hg(2+)-sensitive
      chemosensor. A comparison of this method with some other fluorescence methods for
      the determination of Hg(2+) indicated that this method has high selectivity and
      good water solubility. The analytical performance characteristics of the proposed
      Hg(2+)-sensitive chemosensor were investigated. The chemosensor can be applied to
      the quantification of Hg(2+) with a linear range from 6.6 * 10(-7) to 2.4 * 10(
      4) M and a detection limit of 1.3 * 10(-7) M. The experiment results show that
      the response behavior of compound 1 towards Hg(2+) is pH independent in neutral
      conditions (pH 5.0-9.0). Most importantly, the fluorescence changes of the
      chemosensor are remarkably specific for Hg(2+) in the presence of other metal
      ions, which meet the selective requirements for practical application. Moreover,
      the response of the chemosensor toward Hg(2+) is fast (response time less than 1
      min). In addition, the chemosensor has been used for the determination of Hg(2+)
      in river water samples with satisfactory results.

PMID- 24025575
TI  - Hyperchromisity and molecular recognition of a novel modified beta-cyclodextrin
      tethering with phenylaminoazobenzene.
AB  - A modified beta-cyclodextrin (1) tethered with a phenylaminoazobenzen moiety has
      been synthesized for the purpose of developing a new guest-responsive color
      change chemosensor. When the solution became acidic, 1 changed color from yellow
      to purple due to a structural change of the dye moiety from the azo form to the
      azonium one by protonation on the azo group. However, the pH titration curve of 1
      was affected by the presence of the guest, as shown by the fact that the curve in
      the acidic region shifted to the neutral side by the presence of 1-adamantanol.
      This suggests that 1 has a potential to show a guest-induced absorption variation
      under the acidic condition. Upon guest addition at pH 0.61 at the concentration
      of 1 with 1 * 10(-5) M, 1 showed a colorless-to-color change. Such
      hyperchromisity in the absorption spectrum of 1 is associated with a guest
      induced conformational change of the dye moiety from inside to outside of the CD
      cavity, and is used for molecular sensing. Among various guests, 1 was found to
      be highly sensitive to a steroidal guest having a C12 hydroxyl group in the
      framework, such as ursodeoxycholic acid and lithocholic acid in an acidic aqueous
      solution. 

PMID- 24025576
TI  - Effects of surfactants and electrolytes on chemical oscillation at a
      water/nitrobenzene interface investigated by quasi-elastic laser scattering
      method.
AB  - We used a time-resolved interfacial tension measurement method with quasi-elastic
      laser scattering to investigate the effects of electrolytes and various
      surfactants on the nonlinear dynamics of the chemical oscillation that occurred
      at a water/nitrobenzene interface when a surfactant was added to the interface
      through a capillary. For both cationic and anionic surfactants, an electrolyte in
      the water phase was required for slow desorption of the surfactant from the
      interface. In the absence of an electrolyte, repulsion between the polar head
      groups of the ionic surfactants hindered adsorption of the surfactant molecules
      at the interface, resulting in their rapid desorption. In contrast, the presence
      of an electrolyte induced adsorption of the surfactant ions by screening their
      charged polar heads. Zwitterionic and nonionic surfactants were also examined and
      we deduced that the salting out effect of the surfactant produced by the presence
      of an electrolyte results in strongly attractive interactions between the
      surfactant molecules and the water/nitrobenzene interface. 

PMID- 24025577
TI  - Determination of isotianil in brown rice and soil using supercritical fluid
      extraction and gas chromatography/mass spectrometry.
AB  - Isotianil (3,4-dichloro-2'-cyano-1,2-thiazole-5-carboxanilide) is a new plant
      activating pesticide. Usage of the pesticide was approved for rice fields in 2010
      and its production increased 400 times (2 * 10(4) kg) in the next year. In this
      work, a method for determining isotianil in brown rice and rice field soil was
      investigated for the first time. Isotianil was extracted by supercritical fluid
      extraction and measured by gas chromatography/mass spectrometry. Isotianil was
      successfully analyzed with good recoveries (95.1-99.3%) even from soil samples
      with strong adsorption of pesticides.

PMID- 24025578
TI  - Molecular characterization of organic nitrogen in cattle manure compost by size
      exclusion HPLC with chemiluminescent nitrogen detection.
AB  - To characterize organic nitrogen present in cattle manure compost, a hot-water
      extract of the compost along with an acid-insoluble (humic acid-like) fraction
      either treated with alkali or laccase or untreated were separated by size
      exclusion high-performance liquid chromatography (SE-HPLC). Nitrogen was then
      detected by chemiluminescent nitrogen detection (CLND), and humic acid-like
      substances were detected by measuring the absorbance at 420 nm. The acid
      insoluble fraction comprised the higher molecular-weight region in the
      chromatogram of the whole extract, and its chromatogram pattern of CLND was
      similar to that of the absorbance at 420 nm. Changes in the molecular-weight
      distribution of the acid-insoluble fraction detected by CLND due to alkaline
      degradation and laccase polymerization were in agreement with those observed by
      measuring the absorbance at 420 nm. These results, together with other data,
      demonstrate that protein and humic acid-like moieties are present in the same
      molecule in compost organic matter. 

PMID- 24025579
TI  - Development of a membrane-based microwave-mediated electrochemical ELISA method
      for TNF-alpha detection in patients with periodontitis.
AB  - The tumor necrosis factor-alpha (TNF-alpha) is implicated in periodontal disease,
      and there was an attempt to quantitate it by a membrane-based microwave-mediated
      electrochemical enzyme-linked immunosorbent assay (MMeELISA) using p-aminophenyl
      phosphate (pAPP) with an over-all time of 1.5 h. A differential pulse
      voltammetric signal increased linearly with an increase in the amount of TNF
      alpha with a detection limit of 0.48 pg mL(-1). This bio-sensing platform
      revealed a significant difference in the TNF-alpha level between GCF samples from
      periodontal patients and healthy volunteers. 

PMID- 24025580
TI  - Retraction: Analysis of risedronate and related substances by ion-pair reversed
      phase high-performance liquid chromatography with evaporative light-scattering
      detection.
AB  - This article published in Anal. Sci., 2010, 26(3), 325 was withdrawn by the
      Editor on June 7, 2013, because it was concluded that the author has copied
      significant parts of an earlier paper (Y. Jiang and Z. Xie, Determination of
      Ibandronate and its Degradation Products by Ion-Pair RP LC with Evaporative Light
      Scattering Detection, Chromatographia, 2005, 62, 257, doi: 10.1365/s10337-005
      0618-4). We regret that this was not detected during the reviewing process.

PMID- 24025582
TI  - Management of pediatric type III supracondylar humerus fractures in the United
      States: results of a national survey of pediatric orthopaedic surgeons.
AB  - BACKGROUND: Supracondylar humerus fractures are common injuries in the pediatric
      population. The most severe, type III injuries, have seen the most debate on
      treatment regimens. Traditionally, these fractures were treated as surgical
      emergencies, most often fixed with percutaneous pinning in a cross-pin
      configuration. The recent literature shows that delayed fixation is comparable to
      emergent fixation as long as there is no vascular compromise with the injury.
      METHODS: A short survey was sent to Pediatric Orthopaedic Society of North
      America (POSNA) members using an online survey and questionnaire service. The
      purpose of the survey was to establish an overview of current practices in the
      United States concerning treatment of type III supracondylar humerus fractures
      and the influence of the recent literature on the management of these injuries.
      RESULTS: A total of 309 members, representing a wide range of locations and years
      in practice, responded to our survey. About 81% preferred to splint type III
      supracondylar humerus fractures and plan for fixation the following morning,
      assuming there was no issue necessitating emergent fixation. The preferred method
      of percutaneous fixation was fairly evenly distributed between cross-pin
      configuration (30%), 2 lateral pins (33%), and 3 lateral pins (37%). About 56% of
      those surveyed stated that the recent literature showing comparable outcomes with
      2 lateral pins versus a cross-pin configuration had not changed their approaches
      to management of these fractures concerning the method of fixation. CONCLUSIONS:
      The trend in management of type III supracondylar humerus fractures in children
      is progressing toward delayed treatment and lateral pin configuration. The
      results provide an overview of the current practice of POSNA members concerning
      management of these fractures. We believe this information is beneficial to both
      pediatric-trained and nonpediatric-trained orthopaedic surgeons to help guide
      their decisions when dealing with these injuries. LEVEL OF EVIDENCE: This study
      is a Level V Therapeutic Study reviewing trends in the management of type III
      supracondylar humerus fractures in children. The previously described experts
      represent various levels of expertise in their preferred method of fixation.

PMID- 24025583
TI  - The thyroid cancer PAX8-PPARG fusion protein activates Wnt/TCF-responsive cells
      that have a transformed phenotype.
AB  - A chromosomal translocation results in the production of a paired box 8
      peroxisome proliferator-activated receptor gamma (PAX8-PPARG) fusion protein
      (PPFP) in ~35% of follicular thyroid carcinomas. To examine the role of PPFP in
      thyroid oncogenesis, the fusion protein was stably expressed in the non
      transformed rat thyroid cell line PCCL3. PPFP conferred on PCCL3 cells the
      ability to invade through Matrigel and to form colonies in anchorage-independent
      conditions. PPFP also increased the fraction of cells with Wnt/TCF-responsive
      green fluorescent protein reporter gene expression. This Wnt/TCF-activated
      population was enriched for colony-forming and invading cells. These actions of
      PPFP required a functional PPARG DNA binding domain (DBD) within PPFP and were
      further stimulated by PPARG agonists. These data indicate that PPFP, through its
      PPARG DBD, induces Wnt/TCF pathway activation in a subpopulation of cells, and
      these cells have properties of cellular transformation including increased
      invasiveness and anchorage-independent growth.

PMID- 24025584
TI  - Familial pituitary apoplexy as the only presentation of a novel AIP mutation.

PMID- 24025586
TI  - D-brane solitons and boojums in field theory and Bose-Einstein condensates.
AB  - In certain field theoretical models, composite solitons consisting of a domain
      wall and vortex lines attached to the wall have been referred to as 'D-brane
      solitons'. We show that similar composite solitons can be realized in phase
      separated two-component Bose-Einstein condensates. We discuss the similarities
      and differences between topological solitons in the Abelian-Higgs model and those
      in two-component Bose-Einstein condensates. On the basis of the formulation of
      gauge theory, we introduce the 'boojum charge' to characterize the D-brane
      soliton in Bose-Einstein condensates. 

PMID- 24025585
TI  - Contribution of GTPase activity to LRRK2-associated Parkinson disease.
AB  - Mutations in the leucine-rich repeat kinase 2 (LRRK2, PARK8, OMIM 607060) gene
      represent the most common known cause of hereditary Parkinson's disease (PD) with
      late-onset and dominant inheritance. LRRK2 protein is composed of multiple
      domains including two distinct enzymatic domains, a kinase and a Ras-of-complex
      (Roc) GTPase, connected by a C-terminal-of-Roc (COR) domain, and belongs to the
      ROCO protein family. Disease-causing mutations located in the kinase domain
      enhance kinase activity (i.e., G2019S) whereas mutations clustering within the
      Roc-COR tandem domain impair GTPase activity (i.e., R1441C/G and Y1699C).
      Familial LRRK2 mutations commonly induce neuronal toxicity that, at least for the
      frequent G2019S variant, is dependent on kinase activity. The contribution of
      GTPase activity to LRRK2-dependent neuronal toxicity is not yet clear. Therefore,
      both GTPase and kinase activity may be important for mediating neurodegeneration
      in PD due to familial LRRK2 mutations. At present, the physiological function of
      LRRK2 in the mammalian brain and the regulation of its enzymatic activity are
      incompletely understood. In this review, we focus on the GTPase domain of LRRK2
      and discuss the recent advances in elucidating its function and its interplay
      with the kinase domain for the regulation of LRRK2 activity and toxicity. GTPase
      activity is an important feature of LRRK2 biology and pathophysiology and
      represents an underexplored yet potentially tractable therapeutic target for
      treating LRRK2-associated PD. 

PMID- 24025587
TI  - Expectantly waiting: a survey of thyroid surgery wait times among Canadian
      otolaryngologists.
AB  - BACKGROUND: Our objective is to highlight discrepancies between actual wait times
      and perceived appropriate wait times for various thyroid pathologies among
      Otolaryngology-Head and Neck Surgeons in Canada; and to identify specific
      diagnoses/pathologies where wait times could be improved. METHODS: A
      questionnaire was distributed to all practicing CSO-HNS members. Questions
      focused on actual wait times for initial consults and surgery within individual
      practices, in the setting of various thyroid pathologies. Respondents were also
      asked to state wait times that they felt were appropriate for each scenario.
      Wilcoxon signed-rank tests were performed to determine statistically significant
      differences between actual and appropriate wait times. RESULTS: For most
      scenarios, the actual wait times were significantly longer than most physicians
      felt were appropriate; these scenarios included time to initial consult for
      undiagnosed nodules, time to surgery for confirmed malignancies, and time to
      completion thyroidectomy for surgically confirmed malignancies. CONCLUSIONS: Wait
      times for thyroid consults and surgeries in Canada are longer than physicians
      feel are appropriate. The authors hope that this survey may spur a move towards a
      national consensus on appropriate wait times for the treatment of thyroid
      pathology.

PMID- 24025588
TI  - Immune-relevant and new xenobiotic molecular biomarkers to assess anthropogenic
      stress in seals.
AB  - Harbour seals as top predators and indicators for ecosystem health are exposed to
      increasing pressure caused by anthropogenic activities in their marine
      environment. After their lactation period of about 24 days pups are weaned and
      left to hunt on their own. Little is known about the development of their immune
      system and a better understanding of anthropogenic impacts on the general health
      and immune system of harbour seal pups is needed. mRNA transcription of six
      immuno-relevant biomarkers was analysed in 13 abandoned harbour seal pups from
      the North Sea, fostered at the Seal Centre Friedrichskoog, Germany. RNAlater
      blood samples were taken at admission, day 22 and before release and analysed
      using RT-qPCR. Significant differences in HSP70, cytokine IL-2 and xenobiotic
      biomarkers AHR, ARNT and PPARalpha transcription were found between admission,
      during rehabilitation and before release. Highest levels at admission may result
      from dehydration, handling, transport and contaminant exposure via lactation. The
      significant decrease is linked to health improvement, feeding and adaptation. The
      increase before release is suspected to be due to infection pressure and
      contaminant exposure from feeding on fish. Molecular biomarkers are a sensitive
      tool to evaluate health and pollutant exposure and useful to serve as early
      warning indicators, monitoring and case-by-case tool for marine mammals in human
      care and the wild. 

PMID- 24025589
TI  - MLSTest: novel software for multi-locus sequence data analysis in eukaryotic
      organisms.
AB  - Multi-locus sequence typing (MLST) is a frequently used genotyping method whose
      goal is the unambiguous assignment of microorganisms to genetic clusters. MLST
      typically involves analysis of DNA sequence results generated from several house
      keeping gene loci. MLST remains the gold standard for molecular typing of many
      bacterial pathogens. Eukaryotic pathogens have also been the subject of MLST,
      however, few tools are available to deal with diploid sequence data. Here we
      present novel software for MLST data analysis tailored towards diploid
      Eukaryotes: MLSTest. This software meets various methods used in MLST and
      introduces some novel methodologies for the evaluation of the data set. In
      addition to construction of allelic profiles and basic clustering analysis, the
      MLSTest looks for network structures that suggest genetic exchange in BURST
      graphs. Additionally, it uses several simple methods for tree construction with
      the advantage of managing heterozygous or three-state sites. Additionally, the
      software analyses whether concatenation of fragments from different genes is
      suitable for the data set using different tests (bionj-incongruence length
      difference test, Templeton test). It evaluates how the incongruence is
      distributed across the tree using a variation of the localized incongruence
      length difference test based on a modified neighbour joining algorithm. We tested
      the last method in simulated datasets. We showed that is conservative (adequate
      type I error rate) and moderately to highly powerful as well as useful to
      localize incongruences in two bacterial and two eukaryotic MLST datasets. MLSTest
      was also designed for developing MLST schemes. It thus has tools to optimize
      locus combinations and to reduce the number of targets required for typing.
      MLSTest also analyses whether the discriminatory power of the typing scheme is
      increased by including more loci. We evaluated the software over simulated and
      real datasets from bacterial and eukaryotic microorganisms. The software is
      freely available at http://www.ipe.unsa.edu.ar/software. 

PMID- 24025591
TI  - Ethical issues in research involving minority populations: the process and
      outcomes of protocol review by the Ethics Committee of the Faculty of Tropical
      Medicine, Mahidol University, Thailand.
AB  - BACKGROUND: Recruiting minorities into research studies requires special
      attention, particularly when studies involve "extra-vulnerable" participants with
      multiple vulnerabilities, e.g., pregnant women, the fetuses/neonates of ethnic
      minorities, children in refugee camps, or cross-border migrants. This study
      retrospectively analyzed submissions to the Ethics Committee of the Faculty of
      Tropical Medicine (FTM-EC) in Thailand. Issues related to the process and
      outcomes of proposal review, and the main issues for which clarification/revision
      were requested on studies, are discussed extensively. METHODS: The study data
      were extracted from proposals and amendments submitted to the FTM-EC during the
      period October 2009 - September 2012, and then analyzed qualitatively and
      quantitatively. The main issues for clarification/revision were analyzed by
      thematic content analysis. RESULTS: 373 proposals were submitted; 44 studies
      involved minority groups with 21 extra-vulnerable minorities. All clinical and
      2/3 of non-clinical studies submitted for initial review underwent full-board
      review. For combined clinical and non-clinical study submissions, 92.1% were
      referred back to the investigators and approved after clarification/revision,
      while 2.7% were deferred due to major/critical changes, and 2.1% not approved due
      to substantial violations of ethical principles. The main issues needing
      clarification/revision differed between all studies and those involving
      minorities: participant information sheet (62.2% vs. 86.4%), informed
      consent/assent form (51.2% vs. 86.4%), and research methodology (80.7% vs.
      84.1%), respectively. The main ethical issues arising during the meetings,
      regarding studies involving minorities, included ensuring no exploitation,
      coercion, or pressure on the minority to participate; methodology not affecting
      their legal status; considering ethnicity and cultural structure; and providing
      appropriate compensation. CONCLUSION: Delays in the approval or non-approval of
      studies involving minorities were mainly due to major or minor deviations from
      acceptable ethical standards and/or unclear research methodology. The FTM-EC has
      employed several mechanisms in its operations, including transparency in the
      review process, building good relationships via open communication with
      investigators, requesting investigators to consider closely the necessity to
      enroll minority groups and the risk-benefits for individuals and their
      communities, and the inclusion of minority-community engagement when developing
      the proposal. Other effective activities include annual study-site inspections,
      and offering refresher courses to raise awareness of minority and vulnerability
      issues among researchers.

PMID- 24025592
TI  - Type A aortic dissection after nonaortic cardiac surgery.
AB  - BACKGROUND: Cardiac surgery with cardiopulmonary bypass is associated with
      mechanical manipulation of the ascending aorta that occasionally leads to type A
      aortic dissection (AAD). METHODS AND RESULTS: One hundred three patients with
      surgical repair for AAD following nonaortic cardiac surgery were identified. With
      the use of logistic regression modeling, coronary artery bypass surgery (CABG),
      either isolated or combined with another procedure in the initial operation, was
      associated with significantly higher operative mortality in comparison with
      patients with non-CABG procedures at the time of AAD repair both for all patients
      (odds ratio, 2.90; 95% confidence interval, 1.09-7.72; P=0.033) and for patients
      with acute and chronic AAD>=30 days after the initial operation (odds ratio,
      3.62; 95% confidence interval, 1.13-11.54; P=0.03). In patients who developed AAD
      late after the initial operation, operative mortality was highest in patients
      without preoperative coronary angiography and appropriate management of their
      native coronary artery disease and graft disease (odds ratio, 5.36; 95%
      confidence interval, 1.68-17.0; P=0.002). Nearly all the intimal dissection tears
      were located at sites of previous surgical trauma. Most of the ascending aortas
      that had dissected initially had a diameter>=40 mm with histological evidence of
      medial degeneration in resected tissue samples. CONCLUSIONS: In patients who have
      undergone previous cardiac surgery, preexisting aortic wall pathology contributes
      to AAD with typical intimal damage at sites of mechanical trauma. The operative
      mortality was the highest in patients with previous CABG in comparison with
      patients with non-CABG procedures. Preoperative coronary angiography and
      operative management of native coronary and graft disease were significantly
      associated with outcome in patients with previous CABG.

PMID- 24025590
TI  - Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand
      pathway.
AB  - INTRODUCTION: Cell-based therapy represents a new frontier in the treatment of a
      wide variety of human diseases traditionally associated with morbidity outcomes,
      including those involving inflammation, autoimmunity, tissue damage, and cancer.
      However, the use of mesenchymal stem cells (MSCs) to treat multiple myeloma (MM)
      bone disease has raised concerns. Specifically, evidence has shown that infused
      MSCs might support tumor growth and metastasis. METHODS: In this study, we used a
      standard disseminated MM model in mice to identify the in vivo effects of
      intravenous MSC infusion. In addition, a series of in vitro co-culture assays
      were preformed to explore whether Fas/Fas ligand (Fas-L) is involved in the
      inhibitory effects of MSCs on MM cells. RESULTS: In the MM mouse model, treatment
      of MSCs with highly expressed Fas ligand (Fas-L high MSCs) showed remarkable
      inhibitory effects on MM indenization in terms of extending the mouse survival
      rate and inhibiting tumor growth, bone resorption in the lumbus and collum
      femoris, and MM cell metastasis in the lungs and kidneys. In addition, reduced
      proliferation and increased apoptosis of MM cells was observed when co-cultured
      with Fas-L high MSCs in vitro. Furthermore, mechanistically, the binding between
      Fas and Fas-L significantly induced apoptosis in MM cells, as evidenced through
      an increase in the expression of apoptosis marker and Fas in MM cells. In
      contrast, Fas-L null MSCs promote MM growth. CONCLUSIONS: These data suggest that
      Fas/Fas-L-induced MM apoptosis plays a crucial role in the MSC-based inhibition
      of MM growth. Although whether MSCs inhibit or promote cancer growth remains
      controversial, the levels of Fas-L expression in MSCs determine, at least
      partially, the effects of MSCs on MM cell growth.

PMID- 24025593
TI  - A perfect storm: type A aortic dissection and previous cardiac surgery.

PMID- 24025594
TI  - Risk of lower and upper gastrointestinal bleeding, transfusions, and
      hospitalizations with complex antithrombotic therapy in elderly patients.
AB  - BACKGROUND: Complex antithrombotic therapy (CAT) prescribed to elderly patients
      increases the risk of gastrointestinal bleeding. We quantified upper (UGIE) and
      lower gastrointestinal (LGIE) events, transfusions, and hospitalizations in a
      national cohort of elderly veterans prescribed CAT. METHODS AND RESULTS: Veterans
      >=60 years of age prescribed anticoagulant-antiplatelet, aspirin (ASA)
      antiplatelet, ASA-anticoagulant, or triple therapy (ie, TRIP, anticoagulant
      antiplatelet-ASA) were identified from the national pharmacy database (October 1,
      2002 to September 30, 2008). Prescription-fill data were linked to Veteran
      Affairs and Medicare encounter files, each person-day of follow-up was assessed
      for CAT exposure, and outcomes were defined by using diagnostic code algorithms
      derived following chart abstraction. Incidence density ratios (compared with the
      reference category of no CAT) and survival analysis was conducted. Among 78,133
      veterans (98.6% white; mean age, 72.3 [standard deviation 7.7]), 64% were
      prescribed ASA-antiplatelet and anticoagulant-antiplatelet and 6% were prescribed
      TRIP. The incidence of UGIE was 20.1/1000 patient-years, and the incidence of
      LGIE was 70.1/1000 patient-years. ASA-anticoagulant and TRIP were associated with
      the highest incidence of transfusion and hospitalization. A 40% to 60% increased
      risk of UGIE was observed with all strategies. LGIE was 30% higher with
      anticoagulant-antiplatelet, and transfusion increased with ASA-anticoagulant
      (hazard ratio, 6.1; 95% confidence interval, 5.2-7.1) and TRIP (hazard ratio,
      5.0; 95% confidence interval, 4.2-5.8). Increased risk of hospitalization was
      noted with all strategies. The number needed to harm for UGIE or LGIE ranged from
      52 to 65 and 15 to 23, respectively. The number needed to harm for
      hospitalization was 39 (anticoagulant-antiplatelet), 34 (ASA-anticoagulant), 67
      (ASA-antiplatelet), and 45 (TRIP) patients. CONCLUSIONS: Among elderly patients,
      CAT-related LGIE and UGIE are clinically relevant risks resulting in increased
      hospitalizations and transfusions.

PMID- 24025595
TI  - Monitoring of monocyte recruitment in reperfused myocardial infarction with
      intramyocardial hemorrhage and microvascular obstruction by combined fluorine 19
      and proton cardiac magnetic resonance imaging.
AB  - BACKGROUND: Monocytes and macrophages are indispensable in the healing process
      after myocardial infarction (MI); however, the spatiotemporal distribution of
      monocyte infiltration and its correlation to prognostic indicators of reperfused
      MI have not been well described. METHODS AND RESULTS: With combined fluorine
      19/proton ((1)H) magnetic resonance imaging, we noninvasively visualized the
      spatiotemporal recruitment of monocytes in vivo in a rat model of reperfused MI.
      Blood monocytes were labeled by intravenous injection of (19)F-perfluorocarbon
      emulsion 1 day after MI. The distribution patterns of monocyte infiltration were
      correlated to the presence of microvascular obstruction (MVO) and intramyocardial
      hemorrhage. In vivo, (19)F/(1)H magnetic resonance imaging performed in series
      revealed that monocyte infiltration was spatially inhomogeneous in reperfused MI
      areas. In the absence of MVO, monocyte infiltration was more intense in MI
      regions with serious ischemia-reperfusion injuries, indicated by severe
      intramyocardial hemorrhage; however, monocyte recruitment was significantly
      impaired in MVO areas accompanied by severe intramyocardial hemorrhage. Compared
      with MI with isolated intramyocardial hemorrhage, MI with MVO resulted in
      significantly worse pump function of the left ventricle 28 days after MI.
      CONCLUSIONS: Monocyte recruitment was inhomogeneous in reperfused MI tissue. It
      was highly reduced in MVO areas defined by magnetic resonance imaging. The
      impaired monocyte infiltration in MVO regions could be related to delayed healing
      and worse functional outcomes in the long term. Therefore, monocyte recruitment
      in MI with MVO could be a potential diagnostic and therapeutic target that could
      be monitored noninvasively and longitudinally by (19)F/(1)H magnetic resonance
      imaging in vivo.

PMID- 24025596
TI  - Sensitivity analysis of the relative biological effectiveness predicted by the
      local effect model.
AB  - The relative biological effectiveness (RBE) is a central quantity in particle
      radiobiology and depends on many physical and biological factors. The local
      effect model (LEM) allows one to predict the RBE for radiobiologic experiments
      and particle therapy. In this work the sensitivity of the RBE on its determining
      factors is elucidated based on monitoring the RBE dependence on the input
      parameters of the LEM. The relevance and meaning of all parameters are discussed
      within the formalism of the LEM. While most of the parameters are fixed by
      experimental constraints, one parameter, the threshold dose Dt, may remain free
      and is then regarded as a fit parameter to the high LET dose response curve. The
      influence of each parameter on the RBE is understood in terms of theoretic
      considerations. The sensitivity analysis has been systematically carried out for
      fictitious in vitro cell lines or tissues with alpha/beta = 2 Gy and 10 Gy,
      either irradiated under track segment conditions with a monoenergetic beam or
      within a spread out Bragg peak. For both irradiation conditions, a change of each
      of the parameters typically causes an approximately equal or smaller relative
      change of the predicted RBE values. These results may be used for the assessment
      of treatment plans and for general uncertainty estimations of the RBE. 

PMID- 24025598
TI  - EPR and ESE of CuS4 complex in Cu(dmit)2: g-factor and hyperfine splitting
      correlation in tetrahedral Cu-sulfur complexes.
AB  - Pseudotetrahedral CuS4 complexes of Cu(dmit)2 compound in DMF solution were
      studied by EPR, UV-Vis and electron spin echo methods. After rapid freezing at 77
      K a good glassy state is formed and the CuS4 complex has a D(2d) symmetry of a
      compressed tetrahedron with xy ground state and spin-Hamiltonian parameters
      g||=2.089, g?=2.026, A||=146*10(-4) cm(-1) and A?=30*10(-4) cm(-1). The complex
      is not deformed in the glassy state and is very rigid as indicated by the echo
      detected spectrum and by electron spin relaxation which is governed by
      reorientations of methyl groups of surrounding DMF molecules as shown by electron
      spin echo envelope modulation (ESEEM) spectrum. The g|| and A|| of Cu(dmit)2 and
      other CuS4 complexes collected in Peisach-Blumberg correlation diagram were
      analyzed using extended Molecular Orbital theory. We explain why the correlation
      line for copper-sulfur complexes has larger slope compared to the CuO4 and CuN4
      tetrahedra. Along the correlation line the delocalization of unpaired electron
      density onto ligand is constant and varies from beta=0.78-0.83 for g|| in the
      range 2.06-2.10 of correlation diagram. The slope of the line is determined by
      the product of MO-coefficients alphac1, where alpha is a parameter characterizing
      delocalization of unpaired electron in x(2)-y(2) and c1<1 is a mixing parameter
      decreasing when 4p contribution grows. We found, unexpectedly, that alphac1~0.7
      for all CuS4 complexes suggesting a correlation between degree of tetrahedral
      deformation and MO-parameters. MO-coefficients for Cu(dmit)2 are alpha=0.753,
      beta=0.752 and c1=0.930 confirming a strong delocalization of unpaired electron
      in xy and x(2)-y(2) orbitals.

PMID- 24025597
TI  - Complexities of gender assignment in 17beta-hydroxysteroid dehydrogenase type 3
      deficiency: is there a role for early orchiectomy?
AB  - BACKGROUND: 17beta-Hydroxysteroid dehydrogenase type-3 (17betaHSD-3) deficiency
      is a rare cause of 46,XY disorders of sex development. The enzyme converts
      androstenedione to testosterone, necessary for masculinization of male genitalia
      in utero. 17betaHSD-3 deficiency is frequently diagnosed late, at puberty,
      following virilization, with consequent female-to-male gender reassignment in 39
      64%. The decision for sex of rearing is difficult, especially if diagnosed in
      early childhood. Consensus guidelines are equivocal or support male gender
      assignment. Long-term outcomes data to guide decisions are also lacking; however,
      in the few cases of early diagnosis and orchiectomy, female gender retention
      appears more likely.We report two patients with 17betaHSD-3 deficiency, who
      presented at unusual ages, in whom female gender was chosen. We performed a
      focused literature review and summary of gender outcomes in 17betaHSD-3
      deficiency following early orchiectomy. CASES: Patient A was a phenotypic female
      who presented at one year of age with bilateral inguinal hernias and external
      female genitalia. Testes were identified at surgery. The karyotype was 46,XY. She
      was initially diagnosed with complete androgen insensitivity syndrome; however,
      androgen receptor mutation analysis was negative. Human chorionic gonadotropin
      stimulation yielded a low testosterone: androstenedione ratio (0.6, normal >0.8).
      Genetic testing demonstrated compound heterozygosity for two known mutations of
      the HSD17B3 gene. She underwent bilateral orchiectomy at two years of age.Patient
      B was born with female genitalia and virilized at 13 years of age. She did not
      seek evaluation until 22 years of age. Her karyotype was 46,XY. She had bilateral
      inguinal testes and low testosterone: androstenedione ratio (0.3). HSD17B3 gene
      sequencing showed her to be a compound heterozygote for two known mutations. She
      identified herself as female and underwent bilateral orchiectomy and estrogen
      replacement therapy. CONCLUSIONS: These two patients highlight the complexities
      of diagnosis and management in 17betaHSD-3 deficiency. Although existing data are
      limited, early orchiectomy is likely to result in retention of female gender
      identity, avoiding the complications related to virilization in adolescence. As
      such, it is important to pursue a definitive diagnosis to guide clinical
      decisions, and to have the support and long term follow up with an inter
      disciplinary disorders of sex development team.

PMID- 24025599
TI  - Increased expression of (pro)renin receptor in aldosterone-producing adenomas.
AB  - (Pro)renin receptor ((P)RR) is a specific receptor for renin and prorenin. The
      aim of the present study is to clarify expression and possible pathophysiological
      roles of (P)RR in aldosterone-producing adenomas (APAs) and other adrenal tumors.
      Expression of (P)RR was studied by immunocytochemistry, western blot analysis and
      real-time RT-PCR in adrenal tumor tissues obtained at surgery.
      Immunocytochemistry showed that (P)RR was expressed in normal adrenal glands and
      tumor tissues of adrenocortical tumors including APAs. In the normal adrenal
      glands, positive (P)RR immunostaining was observed in both adrenal cortex and
      medulla, with higher (P)RR immunostaining observed in zona glomerulosa and zona
      reticularis. Positive (P)RR immunostaining was also observed in the
      adrenocortical tumors, with elevated (P)RR immunostaining found in APAs,
      particularly in compact cells. By contrast, no apparent (P)RR immunostaining was
      observed in pheochromocytomas. Western blot analysis showed a band of (P)RR
      protein in normal adrenal glands and adrenocortical tumors at the position of 35
      kDa. The relative expression levels of (P)RR protein were higher in tumor tissues
      of APAs than in attached non-neoplastic adrenal tissues of APAs. Real-time RT-PCR
      showed that expression levels of (P)RR mRNA were significantly increased in tumor
      tissues of APAs compared with other adrenal tumor tissues and attached non
      neoplastic adrenal tissues of APAs. The present study has shown for the first
      time that expression of (P)RR is elevated in tumor tissues of APAs, raising the
      possibility that (P)RR may play pathophysiological roles in APAs, such as
      aldosterone secretion and cell proliferation.

PMID- 24025600
TI  - The DPP-4 inhibitor MK0626 and exercise protect islet function in early pre
      diabetic kkay mice.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitor and exercise have proven to be effective
      treatments for diabetes. However, the effects of these interventions in
      compensatory hyperinsulinemia prediabetic period are unknown. The purpose of this
      study was to determine if these interventions have protective effects on beta
      cell function and preventive effects on the onset of diabetes in prediabetic kkay
      mice. After 2 weeks of high-fat diet feeding, we treated 7-week-old mice with a
      normal diet, high-fat diet, exercise training, or the DPP-4 inhibitor for 8
      weeks. C57BL/6J mice served as a normal control. Kkay mice without intervention
      developed diabetes at week 15, but no diabetic mice were observed in the DPP-4I
      or exercise groups as well as the normal control group. The DPP-4I and exercise
      groups showed improved body weight, blood glucose level, glucose tolerance,
      insulin sensitivity, islet area, and islet morphology. In addition, the
      proportion of Ki67-positive beta-cells in the treatment groups was obviously
      higher than that in the untreated groups. MafA (V-maf musculoaponeurotic
      fibrosarcoma oncogene homolog A) expression in the treated groups increased
      markedly. However PDX-1 (pancreatic and duodenal homeobox-1) expression did not
      differ significantly among the groups. The results show that exercise and DPP-4I
      treatment conducted during the hyperinsulinemic prediabetic stage contribute to
      the maintenance of beta-cell function and morphology, enhance beta-cell
      proliferation, extend the compensatory insulin hypersecretion period, and delay
      disease onset. The expression of PDX-1 was not altered significantly during the
      early stages of diabetes. However, the reduced expression of the insulin
      transcription factor MafA may play an important role in the development of
      prediabetes. 

PMID- 24025601
TI  - Surface swarming motility by Pectobacterium atrosepticum is a latent phenotype
      that requires O antigen and is regulated by quorum sensing.
AB  - We describe a previously cryptic phenotype associated with the opportunistic
      phytopathogen Pectobacterium atrosepticum (Pca): surface swarming. We found that
      when Pca was spotted onto plates containing <0.5% (w/v) agar, the culture
      produced copious amounts of extracellular matrix material containing highly
      motile cells. Once produced, this 'slime layer' spread rapidly across the plate
      either as an advancing front or as tendrils. Transposon mutagenesis was used to
      identify mutants that were affected in swarming. Hypo-swarmer mutants mostly
      carried insertions in a horizontally acquired island (HAI5), which encodes a
      cluster of genes involved in O antigen biosynthesis. Hyper-swarmer mutants mostly
      carried insertions in hexY, a known antagonist of the class I flagellar master
      regulator, FlhD4C2. In addition, we found that the nucleoid protein, histone-like
      nuclear structuring protein 2 (H-NS2), also regulated swarming behaviour. A
      mutant in which hns2 was overexpressed displayed a hyper-swarming phenotype,
      whereas a mutant in which the hns2 ORF was inactivated had a hypo-swarming
      phenotype. Swarming was also regulated by quorum sensing (QS) and by the carbon
      source being utilized. We show, using a range of epistasis experiments, that
      optimal swarming requires both motility and O antigen biosynthesis, and that H
      NS2 and QS both promote swarming through their effects on motility.

PMID- 24025602
TI  - Modelled microgravity cultivation modulates N-acylhomoserine lactone production
      in Rhodospirillum rubrum S1H independently of cell density.
AB  - The photosynthetic alphaproteobacterium Rhodospirillum rubrum S1H is part of the
      Micro-Ecological Life Support System Alternative (MELiSSA) project that is aiming
      to develop a closed life support system for oxygen, water and food production to
      support human life in space in forthcoming long-term space exploration missions.
      In the present study, R. rubrum S1H was cultured in a rotating wall vessel (RWV),
      simulating partial microgravity conditions on Earth. The bacterium showed a
      significant response to cultivation in simulated microgravity at the
      transcriptomic, proteomic and metabolic levels. In simulated microgravity
      conditions three N-acyl-l-homoserine lactones (C10-HSL, C12-HSL and 3-OH-C14-HSL)
      were detected in concentrations that were twice those detected under normal
      gravity, while no differences in cell density was detected. In addition, R.
      rubrum cultivated in modelled microgravity showed higher pigmentation than the
      normal gravity control, without change in culture oxygenation. When compared to
      randomized microgravity cultivation using a random positioning machine,
      significant overlap for the top differentially expressed genes and proteins was
      observed. Cultivation in this new artificial environment of simulated
      microgravity showed new properties of this well-known bacterium, including its
      first, to our knowledge, complete quorum-sensing-related N-acylhomoserine lactone
      profile. 

PMID- 24025603
TI  - Use of a stainless steel washer platform to study Acinetobacter baumannii
      adhesion and biofilm formation on abiotic surfaces.
AB  - Acinetobacter baumannii is a frequent cause of hospital-acquired pneumonia, and
      has recently increased in incidence as the causative agent of severe disease in
      troops wounded in Afghanistan and Iraq. Clinical approaches are limited since A.
      baumannii strains isolated from patients are extremely resistant to current
      antimicrobials. A. baumannii can survive desiccation and during outbreaks has
      been recovered from various sites in the patients' environment. To better
      understand its prevalence in hospital settings, we used a stainless steel washer
      (SSW) platform to investigate A. baumannii biofilm formation on abiotic surfaces.
      Scanning electron microscopy demonstrated that A. baumannii forms strong biofilms
      on stainless steel surfaces. This platform was combined with a colorimetric 2,3
      bis(2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino)carbonyl]-2H-tetrazolium
      hydroxide (XTT) reduction assay to observe the metabolic activity of bacterial
      cells, and to facilitate the manipulation and comparison of multiple A. baumannii
      clinical strains. A strong correlation between XTT and c.f.u. assays was
      demonstrated. To complement the cell viability assays, A. baumannii biofilm mass
      was measured by crystal violet staining. Furthermore, the effect of commonly used
      disinfectants and environmental stressors on A. baumannii biofilms and planktonic
      cells was compared and characterized. Biofilms on SSWs were significantly more
      resistant than their planktonic counterparts, providing additional evidence that
      may allow us to understand the high prevalence of this microbe in hospital
      settings. Our results validate that SSWs are a simple, versatile and innovative
      method to study A. baumannii biofilms in vitro. 

PMID- 24025604
TI  - Regulation of the NADP-glutamate dehydrogenase gene gdhA in Aspergillus nidulans
      by the Zn(II)2Cys6 transcription factor LeuB.
AB  - NADP-dependent glutamate dehydrogenase (NADP-GDH) is a key enzyme in the
      assimilation of alternative nitrogen nutrient sources through ammonium in fungi.
      In Aspergillus nidulans, NADP-GDH is encoded by gdhA. Several transcription
      factors are known to regulate gdhA expression, including AreA, the major
      transcription activator of nitrogen metabolic genes, and TamA, a co-activator of
      AreA. TamA also interacts with LeuB, the regulator of leucine biosynthesis. We
      have investigated the effects of leucine biosynthesis on gdhA regulation, and
      found that leucine regulates the levels of NADP-GDH activity and gdhA expression.
      We show, using mutants with perturbed levels of alpha-isopropylmalate (alpha
      IPM), that this leucine biosynthesis intermediate affects gdhA regulation.
      Leucine regulation of gdhA requires a functional LeuB with an intact Zn(II)2Cys6
      DNA-binding domain. By analysing the prevalence of putative LeuB DNA-binding
      sites in promoters of gdhA orthologues we predict broad conservation of leucine
      regulation of NADP-GDH expression within ascomycetes except in the fusaria and
      fission yeasts. Using promoter mutations in gdhA-lacZ reporter genes we
      identified two sites of action for LeuB within the A. nidulans gdhA promoter.
      These two sites lack sequence identity, with one site conforming to the predicted
      LeuB DNA-binding site consensus motif, whereas the second site is a novel
      regulatory sequence element conserved in Aspergillus gdhA promoters. These data
      suggest that LeuB regulates NADP-GDH expression in response to leucine levels,
      which may act as an important sensor of nitrogen availability. 

PMID- 24025605
TI  - Indole inhibits bacterial quorum sensing signal transmission by interfering with
      quorum sensing regulator folding.
AB  - Quorum sensing (QS)-dependent biofilm formation and motility were controlled by
      AqsR in Acinetobacter oleivorans DR1. QS-controlled phenotypes appeared to be
      inhibited by indole and the aqsR mutant had the same phenotypes. We demonstrated
      that the turnover rate of AqsR became more rapid without the N-acylhomoserine
      lactone (AHL) signal, and that indole could increase the expression of many
      protease and chaperone proteins. The addition of exogenous indole decreased the
      expression of two AqsR-targeted genes: AOLE_03905 (putative surface adhesion
      protein) and AOLE_11355 (L-asparaginase). The overexpression of AqsR in
      Escherichia coli was impossible with the indole treatment. Surprisingly, our
      [(35)S]methionine pulse-labelling data demonstrated that the stability and
      folding of AqsR protein decreased in the presence of indole without changing aqsR
      mRNA expression in E. coli. Interestingly, indole resulted in a loss of TraR
      dependent traG expression in an Agrobacterium tumefaciens indicator strain.
      However, when indole was added after incubation with exogenous AHL, indole could
      not inhibit the TraR-dependent expression of the traG promoter. This indicated
      that AHL-bound TraR could be protective against indole, but TraR without AHL
      could not be active in the presence of indole. Here, we provided evidence for the
      first time showing that the indole effect on QS-controlled bacterial phenotypes
      is due to inhibited QS regulator folding and not a reduced QS signal.

PMID- 24025606
TI  - Screening of promoter-specific transcription factors: multiple regulators for the
      sdiA gene involved in cell division control and quorum sensing.
AB  - Prokaryotic DNA-binding transcription factors (TFs) bind in close vicinity of the
      promoter and regulate transcription through interplay with the DNA-dependent RNA
      polymerase. Promoters associated with the genes involved in stress response have
      recently been found to be under the control of multiple regulators, each
      monitoring one specific environmental condition or factor. In order to identify
      TFs involved in regulation of one specific promoter, we have developed a PS-TF
      (promoter-specific TF) screening system, in which the binding of purified TFs to
      a test promoter was analysed by gel-shift assay. This PS-TF screening system was
      applied for detection of TFs involved in regulation of the promoter for the
      Escherichia coli sdiA gene encoding the master regulator of cell division and
      quorum sensing. After screening of a total of 191 purified TFs (two-thirds of the
      predicted E. coli TFs), at least 15 TFs have been identified to bind to the sdiA
      promoter, including five two-component system (TCS) regulators, ArcA, CpxR, OmpR,
      RcsB and TorR. In this study, we focus on these five TFs for detailed analysis of
      their regulatory roles in vivo. Under normal growth conditions in LB medium, all
      these TFs repressed the sdiA promoter and the repression levels correlated with
      their intracellular levels. Taken together, we propose that these TCS regulators
      repress transcription in vivo of the sdiA gene, ultimately leading to suppression
      of cell division. 

PMID- 24025607
TI  - Effect of ciprofloxacin exposure on DNA repair mechanisms in Campylobacter
      jejuni.
AB  - Ciprofloxacin resistance is common both among animal and human Campylobacter
      jejuni isolates. Resistant isolates are shown to persist even without selection
      pressure. To obtain further insight on effects of ciprofloxacin exposure on C.
      jejuni we compared transcriptional responses of both C. jejuni wild-type strain
      81-176 (ciprofloxacin MIC 0.125 mg l(-1)) and its intermediate ciprofloxacin
      resistant variant P3 (Asp90->Asn in GyrA) in the absence and presence of
      ciprofloxacin. Further, we sequenced the genome of P3 and compared the sequence
      with that of wild-type 81-176. One hour of exposure to 8 mg l(-1) of
      ciprofloxacin did not decrease the viability of the parent strain 81-176.
      Transcriptional analysis revealed that ciprofloxacin exposure caused changes in
      the expression of genes involved in DNA replication and repair. While in the wild
      type the exposure caused downregulation of several genes involved in the control
      of DNA replication and recombination, the genes controlling nucleotide excision
      repair and DNA modification were upregulated in both the wild-type and P3. In
      addition, we observed that ciprofloxacin exposure caused upregulation of genes
      responsible for damage recognition in base excision repair in P3. In contrast,
      without ciprofloxacin exposure, DNA repair mechanisms were substantially
      downregulated in P3. The genome sequence of P3 compared to that of the 81-176
      parental strain had three non-synonymous substitutions and a deletion, revealing
      that the resistant variant had maintained genetic integrity. In conclusion,
      enhanced DNA repair mechanisms under ciprofloxacin exposure might explain
      maintenance of genomic integrity in ciprofloxacin-resistant variant P3. 

PMID- 24025608
TI  - Cryotolerance and global gene-expression patterns of Bos taurus indicus and Bos
      taurus taurus in vitro- and in vivo-produced blastocysts.
AB  - In a 2*2 factorial experimental design, embryo development, cryotolerance and
      global gene expression of Nellore (Bos taurus indicus) and Simmental (Bos taurus
      taurus) blastocysts produced in vitro (IVP) and in vivo (multiple ovulation
      derived embryo, MODE) were assessed. Blastocyst production was higher in Nellore
      than in Simmental (47.7+/-2.0% vs 27.0+/-2.0%) cows. The total numbers of ova or
      embryos recovered (5.5+/-0.9 vs 3.7+/-0.8) and transferable embryos (3.8+/-1.0 vs
      2.3+/-0.8) per cow were not different between breeds. Simmental and MODE (34.6%
      and 38.5%, n=75 and 70) blastocysts had higher survival rates after
      cryopreservation compared with Nellore and IVP (20.2% and 18.1%, n=89 and 94)
      embryos, respectively. Differences between transcriptomes were addressed by
      principal-component analysis, which indicated that gene expression was affected
      by subspecies (158 genes), origin (532 genes) and interaction between both
      subspecies and origin (53 genes). Several functional processes and pathways
      relevant to lipid metabolism and embryo viability involving differentially
      expressed genes were identified. The lipid metabolism-related genes were
      upregulated in Simmental (AUH and ELOVL6) and IVP (ACSL3 and ACSL6) blastocysts.
      The expression profiles of genes related to mitochondrial metabolism (ATP5B),
      oxidative stress (GPX4), apoptosis (DAD1, DAP, PRDX2), heat shock (HSPA5),
      pregnancy (IFNT2, PAG2) and cell differentiation (KRT18) varied between
      experimental groups. 

PMID- 24025610
TI  - Paratesticular fibrous pseudotumor in young males presenting with histological
      features of IgG4-related disease: two case reports.
AB  - INTRODUCTION: Paratesticular fibrous pseudotumors represent benign new growths
      confined to intrascrotal structures. Both pathogenesis and clinical management
      are little understood due to the rarity of the lesion, with less than 200 cases
      reported to date. Recently, paratesticular fibrous pseudotumors have been
      postulated to be immunoglobulin G4-related, pathogenetically. Here we report two
      cases of patients with paratesticular fibrous pseudotumor to highlight the
      clinical features of this rare disease and we report the immunohistochemical
      examinations to support the theory of paratesticular fibrous pseudotumor being an
      immunoglobulin G4-related disease. CASE PRESENTATIONS: A 28-year-old white man
      presented with a painless intrascrotal mass. After a clinical examination, a
      malignant growth was suspected. His ultrasound results revealed a well-demarcated
      hypoechoic lesion of 1.5cm in diameter at the spermatic cord. Our patient
      underwent local excision. His follow-up has been uneventful for 12 years. The
      second case was an 18-year-old white man who presented with a painless scrotal
      mass suspicious of testicular tumor. A magnetic resonance imaging scan revealed a
      3cm mass at the spermatic cord with very low signal density on T2-weighted
      imaging and a low and inhomogeneous uptake of gadolinium contrast agent on T1
      weighted, fat-suppressed imaging. Following local excision, our patient has been
      well for 18 months.On histological examination, both of the lesions consisted of
      collagen-rich hyalinized fibrotic tissue with storiform features. There were
      lymphofollicular infiltrates and, sporadically, also venulitis. The
      immunoglobulin G4 staining (in case 2) showed an infiltrate of 10 to 15 positive
      cells per high-power field on average, corresponding to a proportion of 40% in
      evaluable hot spots. The two patients with paratesticular fibrous pseudotumor
      presented within a time span of 15 years. During that time, 400 patients with
      testicular germ cell tumors had been treated in our institution. CONCLUSIONS: The
      specific histological features documented in our case lend support to the theory
      of paratesticular fibrous pseudotumor being an immunoglobulin G4-related
      sclerosing disorder. Paratesticular fibrous pseudotumors usually occur in young
      adulthood. Clinically, paratesticular fibrous pseudotumor can mimic testicular
      malignancy. Ultrasonographic findings are largely unspecific, however, scrotal
      magnetic resonance imaging may aid in discriminating the lesion from malignant
      tumors. Local excision, whenever technically feasible, is the preferred treatment
      of paratesticular fibrous pseudotumor.

PMID- 24025609
TI  - Triggering of suicidal erythrocyte death by celecoxib.
AB  - The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib triggers apoptosis of
      tumor cells and is thus effective against malignancy. The substance is at least
      partially effective through mitochondrial depolarization. Even though lacking
      mitochondria, erythrocytes may enter apoptosis-like suicidal death or eryptosis,
      which is characterized by cell shrinkage and by phosphatidylserine translocation
      to the erythrocyte surface. Eryptosis may be triggered by increase of cytosolic
      Ca2+-activity ([Ca2+]i). The present study explored whether celecoxib stimulates
      eryptosis. Forward scatter was determined to estimate cell volume, annexin V
      binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release
      to depict hemolysis, and Fluo3-fluorescence to quantify [Ca2+]i. A 48 h exposure
      of human erythrocytes to celecoxib was followed by significant increase of
      [Ca2+]i (15 uM), significant decrease of forward scatter (15 uM) and significant
      increase of annexin-V-binding (10 uM). Celecoxib (15 uM) induced annexin-V
      binding was blunted but not abrogated by removal of extracellular Ca2+. In
      conclusion, celecoxib stimulates suicidal erythrocyte death or eryptosis, an
      effect partially due to stimulation of Ca2+ entry. 

PMID- 24025611
TI  - Antenatal management of recurrent fetal goitrous hyperthyroidism associated with
      fetal cardiac failure in a pregnant woman with persistent high levels of thyroid
      stimulating hormone receptor antibody after ablative therapy.
AB  - High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in
      patients with Graves' disease could cause fetal hyperthyroidism during pregnancy.
      Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth
      restriction, advanced bone maturation, cardiomegaly, and fetal death. The
      recognition and treatment of fetal hyperthyroidism are believed to be important
      to optimize growth and intellectual development in affected fetuses. We herein
      report a case of fetal treatment in two successive siblings showing in utero
      hyperthyroid status in a woman with a history of ablative treatment for Graves'
      disease. The fetuses were considered in hyperthyroid status based on high levels
      of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac
      failure was observed in the second fetus. With intrauterine treatment using
      potassium iodine and propylthiouracil, fetal cardiac function improved. A high
      level of TRAb was detected in the both neonates. To the best of our knowledge,
      this is the first report on the changes of fetal cardiac function in response to
      fetal treatment in two siblings showing in utero hyperthyroid status. This case
      report illustrates the impact of prenatal medication via the maternal circulation
      for fetal hyperthyroidism and cardiac failure. 

PMID- 24025612
TI  - Nocturnal intermittent hypoxia is independently associated with pain in subjects
      suffering from sleep-disordered breathing.
AB  - BACKGROUND: On the basis of experimental and clinical evidence, the authors
      hypothesized that nocturnal hypoxemia would be associated with pain reports in
      subjects suffering from sleep-disordered breathing, independently of sleep
      fragmentation and inflammation. METHODS: After obtaining institutional approval
      and access to the Cleveland Family Study phenotype and genotype data, the authors
      used proportional odds regression to examine the association between arterial
      desaturation and four different types of pain, as well as their composite
      measure, sequentially adjusted for: (1) clinical characteristics and (2) sleep
      fragmentation and inflammation. The authors also examined the association of
      selected candidate single-nucleotide polymorphisms with pain reports. RESULTS:
      Decreased minimum nocturnal arterial saturation increased the odds for morning
      headache (adjusted odds ratio per SD=1.36; 95% CI [1.08-1.71]; P=0.009), headache
      disrupting sleep (1.29 [1.10-1.51]; P=0.002), and chest pain while in bed (1.37
      [1.10-1.70]; P=0.004). A decrease in the minimum nocturnal saturation from 92 to
      75% approximately doubled the odds for pain. One single-nucleotide polymorphism
      for the alpha 1 chain of collagen type XI (COL11A1-rs1676486) gene was
      significantly associated with headache disrupting sleep (odds ratio=1.72 [1.01
      2.94]; P=0.038), pain disrupting sleep (odds ratio=1.85 [1.04-3.28]; P=0.018),
      and pain composite (odds ratio=1.89 [1.14-3.14]; P=0.001). CONCLUSION: Nocturnal
      arterial desaturation may be associated with an increased pain in subjects with
      sleep-disordered breathing, independently of sleep fragmentation and
      inflammation.

PMID- 24025615
TI  - Images in anesthesiology: pediatric tongue injury after transesophageal
      echocardiography for cardiac transplantation.

PMID- 24025617
TI  - Enabling reimbursement to health departments for immunization services.
AB  - Through its Billables Project, the Centers for Disease Control and Prevention is
      helping US health departments to implement programs to bill Medicaid, Medicare,
      and private insurance for vaccine costs and administration fees for insured
      clients. A 2001 national survey published in the American Journal of Preventive
      Medicine found that only 31% of US health departments were billing managed care
      organizations for the immunization services they provided to insured patients. By
      developing billing systems, health departments have found a new stream of
      revenue. Funds generated through billing programs can be used for enhanced
      immunization services for children, adolescents, and adults.

PMID- 24025616
TI  - Positive end-expiratory pressure increments during anesthesia in normal lung
      result in hysteresis and greater numbers of smaller aerated airspaces.
AB  - BACKGROUND: Although it is recognized that pulmonary hysteresis can influence the
      effects of positive end-expiratory pressure (PEEP), the extent to which expansion
      of previously opened (vs. newly opening) peripheral airspaces contribute to
      increased lung volume is unknown. METHODS: Following a recruitment maneuver, rats
      were ventilated with constant tidal volumes and imaged during ascending and
      descending ramps of PEEP. RESULTS: The authors estimated peripheral airspace
      dimensions by measuring the apparent diffusion coefficient of He in 10 rats. In a
      separate group (n = 5) undergoing a similar protocol, the authors used
      computerized tomography to quantify lung volume. Hysteresis was confirmed by
      larger end-inspiratory lung volume (mean +/- SD; all PEEP levels included): 8.4
      +/- 2.8 versus 6.8 +/- 2.0 ml (P < 0.001) and dynamic compliance: 0.52 +/- 0.12
      versus 0.42 +/- 0.09 ml/cm H2O (P < 0.001) during descending versus ascending
      PEEP ramps. Apparent diffusion coefficient increased with PEEP, but it was
      smaller during the descending versus ascending ramps for corresponding levels of
      PEEP: 0.168 +/- 0.019 versus 0.183 +/- 0.019 cm/s (P < 0.001). Apparent diffusion
      coefficient was smaller in the posterior versus anterior lung regions, but the
      effect of PEEP and hysteresis on apparent diffusion coefficient was greater in
      the posterior regions. CONCLUSIONS: The authors' study results suggest that in
      healthy lungs, larger lung volumes due to hysteresis are associated with smaller
      individual airspaces. This may be explained by opening of previously nonaerated
      peripheral airspaces rather than expansion of those already aerated. Setting PEEP
      on a descending ramp may minimize distension of individual airspaces.

PMID- 24025618
TI  - Kibble-Zurek scaling and string-net coarsening in topologically ordered systems.
AB  - We consider the non-equilibrium dynamics of topologically ordered systems driven
      across a continuous phase transition into proximate phases with no, or reduced,
      topological order. This dynamics exhibits scaling in the spirit of Kibble and
      Zurek but now without the presence of symmetry breaking and a local order
      parameter. The late stages of the process are seen to exhibit a slow, coarsening
      dynamics for the string-net that underlies the physics of the topological phase,
      a potentially interesting signature of topological order. We illustrate these
      phenomena in the context of particular phase transitions out of the Abelian Z2
      topologically ordered phase of the toric code/Z2 gauge theory, and the non
      Abelian SU(2)k ordered phases of the relevant Levin-Wen models. 

PMID- 24025619
TI  - HIV/AIDS knowledge, attitude and practice among women in the least and most
      HIV/AIDS affected regions of mainland Tanzania.
AB  - Among women in mainland Tanzania, Iringa region in the southern highlands has the
      highest HIV/AIDS prevalence rate while Arusha region in the north-east has the
      lowest prevalence rate. In a 2007/8 survey, Iringa's HIV rate for women was 18.6%
      versus 0.8% in Arusha. Using data from a survey of women aged 15-49 years
      conducted in 2009 by the Champion project of EngenderHealth, a comparison was
      made of HIV/AIDS knowledge, attitude and practice between women in Iringa and
      Arusha regions. It was found that women in Arusha region had more knowledge of
      HIV/AIDS than women in Iringa region, and that more than three-quarters of the
      women in each region were married and 12% of the women in Arusha region had never
      been married compared with 8% of the women in Iringa region. The majority of
      women in each region had at least primary school education and there was no
      significant difference between their educational levels. Women in Arusha region
      were economically less active than women in Iringa region, a statistically
      significant association. More women in Arusha region than in Iringa region had
      never had children (24% versus 12%). Similarly, women in Arusha region had
      significantly fewer children compared with women in Iringa.

PMID- 24025620
TI  - Poly(L-glutamic acid)/chitosan polyelectrolyte complex porous microspheres as
      cell microcarriers for cartilage regeneration.
AB  - In this study a novel kind of porous poly(l-glutamic acid) (PLGA)/chitosan
      polyelectrolyte complex (PEC) microsphere was developed through electrostatic
      interaction between PLGA and chitosan. By adjusting the formula parameters
      chitosan microspheres with an average pore size of 47.5 +/- 5.4 MUm were first
      developed at a concentration of 2 wt.% and freeze temperature of -20  degrees C.
      For self-assembly of the PEC microspheres porous chitosan microspheres were then
      incubated in PLGA solution at 37  degrees C. Due to electrostatic interaction a
      large amount of PLGA (110.3 MUg mg(-1)) was homogeneously absorbed within the
      chitosan microspheres. The developed PEC microspheres retained their original
      size, pore diameters and interconnected porous structure. Fourier transform
      infrared spectroscopy, thermal gravimetric analysis and zeta potential analysis
      revealed that the PEC microspheres were successfully prepared through
      electrostatic interaction. Compared with microspheres fabricated from chitosan,
      the porous PEC microspheres were shown to efficiently promote chondrocyte
      attachment and proliferation. After injection subcutaneously for 8 weeks PEC
      microspheres loaded with chondrocytes were found to produce significant more
      cartilaginous matrix than chitosan microspheres. These results indicate that
      these novel fabricated porous PLGA/chitosan PEC microspheres could be used as
      injectable cell carriers for cartilage tissue engineering.

PMID- 24025621
TI  - Frozen section analysis and sentinel lymph node biopsy in well differentiated
      thyroid cancer.
AB  - BACKGROUND: The aim of this study is to prospectively review the role of sentinel
      lymph node (SLN) biopsy in the management of well differentiated thyroid
      carcinoma (WDTC), and to determine the efficacy of intraoperative frozen section
      analysis at detecting SLN metastasis and central compartment involvement.
      METHODS: The SLN biopsy protocol using 1% methylene blue was performed in 300
      patients undergoing thyroidectomy for WDTC. A limited pretracheal central
      compartment neck dissection (CCND) was performed on all patients. Lymph nodes
      staining blue were considered as SLN's. Both frozen and permanent section
      analyses were performed. RESULTS: SLN's with metastasis were found in 14.3%
      (43/300) of cases. Of this, 11% (33/300) were positive on intraoperative frozen
      section analysis. Frozen section results failed in predicting central compartment
      involvement in 15 cases (5%) whereas central neck compartment involvement was
      missed in 5 cases (1.7%) when based on permanent section results. On frozen
      section analysis, the sensitivity, specificity, positive predictive value and
      negative predictive value (95% CI) of our SLN biopsy technique aiming to remove
      all disease from the central compartment was 68.8% (53.6-80.9), 100% (98.1-100),
      100% (87.0-100) and 94.4% (90.7-96.7) respectively with P < 0.0001. On permanent
      section analysis, the values were 89.6% (76.6-96.1), 100% (98.1-100), 100% (89.8
      100), and 98.1% (95.3-99.3) with P < 0.0001. CONCLUSION: This data series
      demonstrates that patients with WDTC have positive SLN's in 14.3% of cases.
      Moreover, when the SLN's are negative for metastasis on frozen section, the
      central compartment was disease-free in 94.4% of cases. Finally, this study shows
      that 23.3% of positive SLN's were false negatives on intraoperative frozen
      section. According to this data, SLN involvement is an accurate predictor of
      central compartment metastasis, however surgeons should use caution when relying
      on intraoperative frozen section to determine whether to perform a CCND.

PMID- 24025622
TI  - Taking part in a pharmacogenetic clinical trial: assessment of trial participants
      understanding of information disclosed during the informed consent process.
AB  - BACKGROUND: This study is the first to examine the understandings that
      participants have of the consent process in a pharmacogenetic trial of anti
      depressant medication. METHODS: This was a qualitative cross sectional study.
      There were 76 participants residing in London, Mannheim, Arhuus and Poznan.
      RESULTS: Only one quarter of participants (none in Poznan) could articulate the
      concept of pharmacogenetics. Heritability and testing medication were also given
      as the purpose of the trial. Most participants had not appreciated harms that
      could derive from the trial. Even when shown the consent sheet, participants were
      confused about DNA profiling. There was evidence that participants appreciated
      weekly contact with researchers. Most said they would participate in a trial
      again but would like choice over the intervention they were assigned to.
      CONCLUSION: Participants in this study showed a poor level of informed consent.
      Although this is not the first time this argument has been made, it is in the
      case of a pharmacogenetic trial. Further work should investigate the associations
      between extraneous factors such as information and social support on beneficial
      or untoward outcomes of antidepressant treatment.

PMID- 24025623
TI  - Deriving effective atomic numbers from DECT based on a parameterization of the
      ratio of high and low linear attenuation coefficients.
AB  - Dual energy computed tomography (DECT) can provide simultaneous estimation of
      relative electron density rhoe and effective atomic number Zeff. The ability to
      obtain these quantities (rhoe, Zeff) has been shown to benefit selected
      radiotherapy applications where tissue characterization is required. The
      conventional analysis method (spectral method) relies on knowledge of the CT
      scanner photon spectra which may be difficult to obtain accurately. Furthermore
      an approximate empirical attenuation correction of the photon spectrum through
      the patient is necessary. We present an alternative approach based on a
      parameterization of the measured ratio of low and high kVp linear attenuation
      coefficients for deriving Zeff which does not require the estimation of the CT
      scanner spectra. In a first approach, the tissue substitute method (TSM), the
      Rutherford parameterization of the linear attenuation coefficients was employed
      to derive a relation between Zeff and the ratio of the linear attenuation
      coefficients measured at the low and high kVp of the CT scanner. A phantom
      containing 16 tissue mimicking inserts was scanned with a dual source DECT
      scanner at 80 and 140 kVp. The data from the 16 inserts phantom was used to
      obtain model parameters for the relation between Zeff and [Formula: see text].
      The accuracy of the method was evaluated with a second phantom containing 4
      tissue mimicking inserts. The TSM was compared to a more complex approach, the
      reference tissue method (RTM), which requires the derivation of stoichiometric
      fit parameters. These were derived from the 16 inserts phantom scans and used to
      calculate CT numbers at 80 and 140 kVp for a set of tabulated reference human
      tissues. Model parameters for the parameterization of [Formula: see text] were
      estimated for this reference tissue dataset and compared to the results of the
      TSM. Residuals on Zeff for the reference tissue dataset for both TSM and RTM were
      compared to those obtained from the spectral method. The tissue substitutes were
      well fitted by the TSM with R(2) = 0.9930. Residuals on Zeff for the phantoms
      were similar between the TSM and spectral methods for Zeff < 8 while they were
      improved by the TSM for higher Zeff. The RTM fitted the reference tissue dataset
      well with R(2) = 0.9999. Comparing the Zeff extracted from TSM and the more
      complex RTM to the known values from the reference tissue dataset yielded errors
      of up to 0.3 and 0.15 units of Zeff respectively. The parameterization approach
      yielded standard deviations which were up to 0.3 units of Zeff higher than those
      observed with the spectral method for Zeff around 7.5. Procedures for the DECT
      estimation of Zeff removing the need for estimates of the CT scanner spectra have
      been presented. Both the TSM and the more complex RTM performed better than the
      spectral method. The RTM yielded the best results for the reference human tissue
      dataset reducing errors from up to 0.3 to 0.15 units of Zeff compared to the
      simpler TSM. Both TSM and RTM are simpler to implement than the spectral method
      which requires estimates of the CT scanner spectra. 

PMID- 24025624
TI  - Arginine rich short linear motif of HIV-1 regulatory proteins inhibits dicer
      dependent RNA interference.
AB  - BACKGROUND: Arginine Rich Motif (ARM) of HIV-1 Tat and Rev are extensively
      studied linear motifs (LMs). They are already established as an inefficient
      bipartite nuclear localisation signal (NLS). The unusual passive diffusion of HIV
      1 NLS tagged reporter proteins across the nucleus is due to an unknown competing
      functionality of ARM. Recent findings about the role of retroviral proteins as a
      suppressor of RNA interference (RNAi) involving their basic residues hint an
      interesting answer to this alternate functionality. The present work explores the
      role of HIV-1 ARM as a uniquely evolved viral motif to combat Dicer dependent
      RNAi. RESULTS: We show that RNA binding ARM of both HIV-1 Tat and Rev is a LM
      with a pattern RXXRRXRRR unique to viruses. Extending the in silico results to
      wet lab, we proved both HIV-1 Tat and Rev can suppress Dicer dependent RNA
      silencing process involving ARM. We show, HIV-1 Tat and Rev and their
      corresponding ARM can bind the RISC loading complex (RLC) components TRBP and
      PACT confirming ARM as an independent RNAi suppression motif. Enhancement of RNAi
      in infection scenario through enoxacin increases HIV-1 replication as indicated
      by p24 levels. Except Dicer, all other cytoplasmic RNAi components enhance HIV-1
      replication, indicating crucial role of Dicer independent (Ago2 dependent) RNAi
      pathway in HIV-1 infection. Sequence and structural analysis of endo/exo-microRNA
      precursors known to be regulated in HIV-1 infection highlights differential
      features of microRNA biogenesis. One such set of miRNA is viral TAR encoded HIV-1
      miR-TAR-5p (Tar1) and HIV-1-miR-TAR-3p (Tar2) that are known to be present
      throughout the HIV-1 life cycle. Our qPCR results showed that enoxacin increases
      Tar2 miRNA level which is interesting as Tar2 precursor shows Ago2 dependent
      processing features. CONCLUSIONS: We establish HIV-1 ARM as a novel viral motif
      evolved to target the Dicer dependent RNAi pathway. The conservation of such
      motif in other viral proteins possibly explains the potent suppression of Dicer
      dependent RNAi. Our model argues that HIV-1 suppress the processing of siRNAs
      through inhibition of Dicer while at the same time manipulates the RNAi machinery
      to process miRNA involved in HIV-1 replication from Dicer independent pathways.

PMID- 24025625
TI  - Stegomyia mosquitoes in Mayotte, taxonomic study and description of Stegomyia pia
      n. sp.
AB  - Four mosquito species, including a new species of the genus Stegomyia, are
      reported from Mayotte in the western Indian Ocean. The most abundant species were
      Stegomyia aegypti and St. albopicta. Only one species of the St. simpsoni group
      was observed, St. bromeliae. The fourth species is Stegomyia pia Le Goff & Robert
      n. sp. of which the larva, pupa, male and female are here described. The larval
      stages of St. pia n. sp. are morphologically similar to St. aegypti but differ in
      the number of branches of the seta 1-X; the adult is morphologically distinct for
      a number of characters, for instance the scutal ornamentation. Stegomyia pia n.
      sp. is uncommon but not rare, and largely distributed across Mayotte. Its larval
      habitats are natural and diverse including rock pools, tree holes, and cut and
      severed bamboos. The biology of adults remains unknown, especially female biting
      behaviour. Both morphological characters and nucleotide sequences of the ITS2 and
      COI genes indicate that this species is best placed in the genus Stegomyia.
      Dichotomous keys to the four species of Mayotte Stegomyia are presented for
      adults and fourth-instar larvae. The potential vector role of these mosquitoes is
      hypothesised. This paper underlines advances in knowledge of the biodiversity in
      the French overseas departments and territories. 

PMID- 24025626
TI  - Cobalamin supplementation improves motor development and regurgitations in
      infants: results from a randomized intervention study.
AB  - BACKGROUND: During infancy, minor developmental delays and gastrointestinal
      complaints are common, as is a biochemical profile indicative of impaired
      cobalamin status. OBJECTIVE: We investigated whether cobalamin supplementation
      can improve development or symptoms in infants with biochemical signs of impaired
      cobalamin function and developmental delay or feeding difficulties. DESIGN:
      Infants <8 mo of age (n = 105) who were referred for feeding difficulties, subtle
      neurologic symptoms, or delayed psychomotor development were assessed for
      cobalamin status [by the measurement of serum cobalamin, plasma total
      homocysteine (tHcy), and plasma methylmalonic acid (MMA)]. Infants with
      biochemical signs of impaired cobalamin function, defined as a plasma tHcy
      concentration >=6.5 MUmol/L (n = 79), were enrolled in a double-blind, randomized
      controlled trial to receive 400 MUg hydroxycobalamin intramuscularly (n = 42) or
      a sham injection (n = 37). Motor function [Alberta Infants Motor Scale (AIMS)]
      and clinical symptoms (parental questionnaire) were recorded at entry and after 1
      mo. RESULTS: During follow-up, cobalamin supplementation changed all markers of
      impaired cobalamin status (ie, plasma tHcy decreased by 54%, and MMA decreased by
      84%), whereas no significant changes were seen in the placebo group (P < 0.001).
      The median (IQR) increase in the AIMS score was higher in the cobalamin group
      than in the placebo group [7.0 (5.0, 9.0) compared with 4.5 (3.3, 6.0); P =
      0.003], and a higher proportion showed improvements in regurgitations (69%
      compared with 29%, respectively; P = 0.003). CONCLUSIONS: In infants with
      biochemical signs of impaired cobalamin function, 1 intramuscular injection of
      cobalamin resulted in biochemical evidence of cobalamin repletion and improvement
      in motor function and regurgitations, which suggest that an adequate cobalamin
      status is important for a rapidly developing nervous system. This trial was
      registered at clinicaltrials.gov as NCT00710359 and NCT00710138.

PMID- 24025628
TI  - Effect of iodine supplementation in pregnancy on child development and other
      clinical outcomes: a systematic review of randomized controlled trials.
AB  - BACKGROUND: Routine iodine supplementation during pregnancy is recommended by
      leading health authorities worldwide, even in countries where the iodine status
      of the population is sufficient. OBJECTIVES: We evaluated the efficacy and safety
      of iodine supplementation during pregnancy or the periconceptional period on the
      development and growth of children. Secondary outcomes included pregnancy outcome
      and thyroid function. DESIGN: A systematic review of randomized controlled trials
      (RCTs) was conducted. PUBMED, MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane
      Central Register of Controlled Trials databases were searched to identify
      relevant RCTs. RESULTS: Fourteen publications that involved 8 trials met the
      inclusion criteria. Only 2 included trials reported the growth and development of
      children and clinical outcomes. Iodine supplementation during pregnancy or the
      periconceptional period in regions of severe iodine deficiency reduced risk of
      cretinism, but there were no improvements in childhood intelligence, gross
      development, growth, or pregnancy outcomes, although there was an improvement in
      some motor functions. None of the remaining 6 RCTs conducted in regions of mild
      to moderate iodine deficiency reported childhood development or growth or
      pregnancy outcomes. Effects of iodine supplementation on the thyroid function of
      mothers and their children were inconsistent. CONCLUSIONS: In this review, we
      highlight a lack of quality evidence of the effect of prenatal or
      periconceptional iodine supplementation on growth and cognitive function of
      children. Although contemporary RCTs of iodine supplementation with outcomes
      addressing childhood development are indicated, conduct of such RCTs may not be
      feasible in populations where iodine supplementation in pregnancy is widely
      practiced.

PMID- 24025627
TI  - Human bitter perception correlates with bitter receptor messenger RNA expression
      in taste cells.
AB  - BACKGROUND: Alleles of the receptor gene TAS2R38 are responsible in part for the
      variation in bitter taste perception of 6-n-propylthiouracil (PROP) and
      structurally similar compounds (eg, glucosinolates in cruciferous vegetables). At
      low concentrations, people with the PAV ("taster" amino acid sequence) form of
      TAS2R38 perceive these bitter compounds, whereas most with the AVI ("nontaster"
      amino acid sequence) form do not; heterozygotes (PAV/AVI) show the widest range
      of bitter perception. OBJECTIVES: The objectives were to examine individual
      differences in expression of PAV-TAS2R38 messenger RNA (mRNA) among
      heterozygotes, to test the hypotheses that the abundance of allele-specific gene
      expression accounts for the variation in human bitter taste perception, and to
      relate to dietary intake of bitter-tasting beverages and foods. DESIGN:
      Heterozygous individuals (n = 22) provided psychophysical evaluation of the
      bitterness of PROP, glucosinolate-containing broccoli juice, non-glucosinolate
      containing carrot juice, and several bitter non-TAS2R38 ligands as well as
      dietary recalls. Fungiform taste papillae were examined for allele-specific
      TAS2R38 expression by using quantitative polymerase chain reaction. RESULTS: PAV
      TAS2R38 mRNA expression was measured in 18 of 22 heterozygous subjects. Relative
      expression varied widely and positively correlated with ratings of bitterness
      intensity of PROP (P = 0.007) and broccoli juice (P = 0.004) but not of the
      control solutions carrot juice (P = 0.26), NaCl (P = 0.68), caffeine (P = 0.24),
      or urea (P = 0.47). Expression amounts were related to self-reported recent and
      habitual caffeine intake (P = 0.060, P = 0.005); vegetable intake was too low to
      analyze. CONCLUSIONS: We provide evidence that PAV-TAS2R38 expression amount
      correlates with individual differences in bitter sensory perception and diet. The
      nature of this correlation calls for additional research on the molecular
      mechanisms associated with some individual differences in taste perception and
      food intake. The trial was registered at clinicaltrials.gov as NCT01399944.

PMID- 24025629
TI  - Prediagnostic plasma vitamin C and risk of gastric adenocarcinoma and esophageal
      squamous cell carcinoma in a Chinese population.
AB  - BACKGROUND: China has some of the highest incidence rates for gastric
      adenocarcinoma (GA) and esophageal squamous cell carcinoma (ESCC) in the world.
      Prospective studies suggested that vitamin C may reduce risks; however,
      associations are unclear because of limited sample size. OBJECTIVE: The objective
      was to examine the relation between prediagnostic plasma vitamin C and the risk
      of GA and ESCC. DESIGN: A case-cohort study was used to assess the association
      between prediagnostic plasma vitamin C and incidence of GA (n = 467) and ESCC (n
      = 618) in the General Population Nutrition Intervention Trial. With the use of
      multivariate Cox proportional hazards models, we estimated the HRs and 95% CIs.
      We also conducted a meta-analysis of the literature up to 1 October 2012 on the
      relation between circulating vitamin C and gastric cancer incidence. Two cohort
      studies and the current study were included to assess the body of evidence.
      RESULTS: For GA, each 20-MUmol/L increase in plasma vitamin C was associated with
      a 14% decrease in risk (HR: 0.86; 95% CI: 0.76, 0.96). Compared with individuals
      with low plasma vitamin C concentrations (<=28 MUmol/L), those with normal
      concentrations (>28 MUmol/L) had a 27% reduced risk of GA (HR: 0.73; 95% CI:
      0.56, 0.94). No association between vitamin C concentrations and ESCC was seen.
      Meta-analysis showed that the risk of incident GA among those with the highest
      concentration of plasma vitamin C was 31% lower (random-effects-pooled-odds ratio
      0.69; 95% CI: 0.54, 0.89) than those in the lowest category. CONCLUSION: Our data
      provide evidence that higher circulating vitamin C was associated with a reduced
      risk of incident GA, but no association was seen for ESCC.

PMID- 24025630
TI  - Olive oil aroma extract modulates cerebral blood flow in gustatory brain areas in
      humans.
AB  - BACKGROUND: Low- and high-fat meals affect homeostatic and gustatory brain areas
      differentially. In a previous study, we showed that a high-fat meal decreased
      cerebral blood flow (CBF) in homeostatic brain areas (hypothalamus), whereas a
      low-fat meal increased CBF in gustatory regions (anterior insula). OBJECTIVE: The
      aim of this study was to investigate the long-lasting effect of fat-free flavor
      active compounds of olive oil on the brain and whether those aroma components can
      trigger fat-associated brain responses in homeostatic and gustatory regions.
      DESIGN: Eleven healthy male subjects participated in a functional magnetic
      resonance imaging study. On 2 measurement days, subjects consumed single-blinded
      a plain low-fat yogurt or low-fat yogurt mixed with a fat-free aroma extract of
      olive oil. Resting CBF was measured before and 30 and 120 min after yogurt
      intake. Hunger was rated before each measurement. Blood samples were collected at
      6 time points. RESULTS: The extract-containing yogurt elicited higher CBF in the
      frontal operculum 30 and 120 min after a meal. Furthermore, the activity change
      in the anterior insula after 30 min correlated positively with the glucose change
      in the extract condition only. No effects were observed in the hypothalamus.
      CONCLUSIONS: The anterior insula and the frontal operculum are regarded as the
      primary taste cortex. Modulation of the frontal operculum by the yogurt
      containing the olive oil extract suggests that it might be possible to simulate
      fat-triggered sensations in the brain on the gustatory level, possibly by
      ingredients the body implicitly associates with fat. This trial was registered at
      clinicaltrials.gov as NCT01716286.

PMID- 24025631
TI  - Potassium and fruit and vegetable intakes in relation to social determinants and
      access to produce in New York City.
AB  - BACKGROUND: Potassium-rich diets are inversely associated with blood pressure.
      Potassium intake before this study had not been objectively measured by using
      potassium excretion in a population-based sample in the United States.
      OBJECTIVES: The objectives of the analysis were to 1) report mean potassium
      excretion in a diverse urban population by using 24-h urine collections, 2)
      corroborate potassium excretion by using self-reported fruit and vegetable
      consumption, and 3) characterize associations between potassium excretion and
      socioeconomic indicators and access to produce. DESIGN: Participants were from
      the 2010 Community Health Survey Heart Follow-Up Study-a population-based study
      including data from 24-h urine collections. The final sample of 1656 adults was
      weighted to be representative of New York City (NYC) adults as a whole. RESULTS:
      Mean urinary potassium excretion was 2180 mg/d, and mean self-reported fruit and
      vegetable intake was 2.5 servings/d. Adjusted urinary potassium excretion was 21%
      lower in blacks than in whites (P < 0.001), 13% lower in non-college graduates
      than in college graduates (P < 0.001), and 9% lower in the lowest-income than in
      the highest-income group (P = 0.03). Potassium excretion was correlated with
      fruit and vegetable intake. Most NYC residents reported a <10-min walk to fresh
      fruit and vegetables; this indicator of access was not associated with potassium
      excretion or fruit and vegetable intake. CONCLUSIONS: Potassium intake is low in
      NYC adults, especially in lower socioeconomic groups. Innovative programs that
      increase fruit and vegetable intake may help increase dietary potassium and
      reduce hypertension-related disease. This trial is registered at
      clinicaltrials.gov as NCT01889589.

PMID- 24025632
TI  - Calcium and alpha-tocopherol suppress cured-meat promotion of chemically induced
      colon carcinogenesis in rats and reduce associated biomarkers in human
      volunteers.
AB  - BACKGROUND: Processed meat intake has been associated with increased colorectal
      cancer risk. We have shown that cured meat promotes carcinogen-induced
      preneoplastic lesions and increases specific biomarkers in the colon of rats.
      OBJECTIVES: We investigated whether cured meat modulates biomarkers of cancer
      risk in human volunteers and whether specific agents can suppress cured meat
      induced preneoplastic lesions in rats and associated biomarkers in rats and
      humans. DESIGN: Six additives (calcium carbonate, inulin, rutin, carnosol, alpha
      tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups
      of rats for 14 d, and fecal biomarkers were measured. On the basis of these
      results, calcium and tocopherol were kept for the following additional
      experiments: cured meat, with or without calcium or tocopherol, was given to
      dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human
      volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for
      mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation,
      lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats
      and volunteers. RESULTS: Cured meat increased nitroso compounds and
      lipoperoxidation in human stools (both P < 0.05). Calcium normalized both
      biomarkers in rats and human feces, whereas tocopherol only decreased nitro
      compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05).
      Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon
      in rats compared with nonsupplemented cured meat (P = 0.01). CONCLUSION: Data
      suggest that the addition of calcium carbonate to the diet or alpha-tocopherol to
      cured meat may reduce colorectal cancer risk associated with cured-meat intake.
      This trial was registered at clinicaltrials.gov as NCT00994526.

PMID- 24025633
TI  - Zinc supplementation reduces morbidity and mortality in very-low-birth-weight
      preterm neonates: a hospital-based randomized, placebo-controlled trial in an
      industrialized country.
AB  - BACKGROUND: Zinc plays a pivotal role in the pathogenesis of many diseases and in
      body growth. Preterm neonates have high zinc requirements. OBJECTIVE: The
      objective of the study was to investigate the efficacy of zinc supplementation in
      reducing morbidity and mortality in preterm neonates and to promote growth.
      DESIGN: This was a prospective, double-blind, randomized controlled study of very
      low-birth-weight preterm neonates randomly allocated on the seventh day of life
      to receive (zinc group) or not receive (control group) oral zinc supplementation.
      Total prescribed zinc intake ranged from 9.7 to 10.7 mg/d in the zinc group and
      from 1.3 to 1.4 mg/d in the placebo control group. The main endpoint was the rate
      of neonates with >= 1 of the following morbidities: late-onset sepsis,
      necrotizing enterocolitis, bronchopulmonary dysplasia, periventricular
      leucomalacia, and retinopathy of prematurity. Secondary outcomes were mortality
      and body growth. RESULTS: We enrolled 97 neonates in the zinc group and 96 in the
      control group. Morbidities were significantly lower in the zinc group (26.8%
      compared with 41.7%; P = 0.030). The occurrence of necrotizing enterocolitis was
      significantly higher in the control group (6.3% compared with 0%; P = 0.014).
      Mortality risk was higher in the placebo control group (RR: 2.37; 95% CI: 1.08,
      5.18; P = 0.006). Daily weight gain was similar in the zinc (18.2 +/- 5.6 g . kg
      1 . d-1) and control (17.0 +/- 8.7 g . kg-1 . d-1) groups (P = 0.478).
      CONCLUSION: Oral zinc supplementation given at high doses reduces morbidities and
      mortality in preterm neonates. This trial was registered in the Australian New
      Zealand Clinical Trial Register as ACTRN12612000823875.

PMID- 24025635
TI  - Particle-size-dependent cytokine responses and cell damage induced by silica
      particles and macrophages-derived mediators in endothelial cell.
AB  - Epidemiological evidence reports silica dust exposure has been associated with
      increased risk of cardiovascular diseases, but the mechanisms are largely
      unknown. In this study, endothelial cells were exposed to increasing
      concentrations of two sizes silica particles and the soluble mediators released
      by macrophages treated with the same particles for 24 h. Expression and release
      of cytokines (IL-1beta, TNF-alpha and IL-6) were measured by using ELISA.
      Cytotoxicity was measured by MTT assay and LDH release. We show that both ways
      induced increases in cell toxicity and cytokines in a dose-dependent manner. For
      smaller particles, the soluble mediators are more capable of increasing cytokines
      compared with the effect of particles directly. For larger particles, evaluating
      results of these two ways are similar. Either way, smaller particles make the
      increasing action of cell toxicity and cytokines more remarkable. Our results
      indicate both silica particle and macrophage-derived mediators can induce
      endothelial cell injury and inflammation and demonstrate the potential importance
      of the particle sizes in this effect.

PMID- 24025634
TI  - Dynamic functions of RhoA in tumor cell migration and invasion.
AB  - RhoA is one of the more extensively studied members of the Rho family of small
      GTPase where it is most readily recognized for its contributions to actin-myosin
      contractility and stress fiber formation. Accordingly, RhoA function during cell
      migration has been relegated to the rear of the cell where it mediates retraction
      of the trailing edge. However, RhoA can also mediate membrane ruffling, lamellae
      formation and membrane blebbing, thus suggesting an active role in membrane
      protrusions at the leading edge. With the advent of fluorescence resonance energy
      transfer (FRET)-based Rho activity reporters, RhoA has been shown to be active at
      the leading edge of migrating cells where it precedes Rac and Cdc42 activation.
      These observations demonstrate a remarkable versatility to RhoA signaling, but
      how RhoA function can switch between contraction and protrusion has remained an
      enigma. This review highlights recent advances regarding how the cooperation of
      Rho effector Rhotekin and S100A4 suppresses stress fiber generation to permit
      RhoA-mediated lamellae formation. 

PMID- 24025636
TI  - Mechanisms of kidney toxicity for chromium- and arsenic-based preservatives:
      potential involvement of a pro-oxidative pathway.
AB  - Metals have been extensively used for the preservation of wood. Among metallic
      conservatives, mixtures of chromated copper arsenate (CCA) were thoroughly used.
      However, the release and consequent mobilization of such compounds by biota, may
      culminate in the exertion of toxic chemical effects. The present study intended
      to show the toxicological effects caused by arsenic (7.2 mg/kg body weight),
      chromium (10.2 mg/kg Cr body weight) and the commercial mixture CCA (7.2 mg/kg As
      body weight and 10.2 mg/kg Cr body weight) in mice, namely the oxidative stress
      response (catalase - CAT, glutathione peroxidase - GPx, and glutathione-S
      transferases - GSTs), in kidney tissues. The determination of the tested
      parameters was performed after exposure; organisms were exposed, and then
      sacrificed at two distinct periods, namely 14 and 96 h after the administration
      of toxicants. Exposure to chromium and arsenic induced significant modifications
      in the redox state of the test organisms, evidenced by significant alterations in
      GSTs and GPx activities. No alterations were found concerning the activity of
      catalase. These findings showed that the chemical mixture used as household
      product may exert significant toxicological outcomes in exposed animals, such as
      rodents, conditioning their redox homeostasis and antioxidant response.

PMID- 24025637
TI  - Endothelial function assessment in atherosclerosis: comparison of brachial artery
      flow-mediated vasodilation and peripheral arterial tonometry.
AB  - INTRODUCTION:  Endothelial dysfunction, characterized by the loss of nitric oxide
      bioavailability, is a key element in the pathogenesis of atherosclerosis and an
      important prognostic factor in cardiovascular diseases. Therefore, the
      development of reliable, safe, and noninvasive methods of endothelial function
      assessment is important for their use in cardiovascular risk stratification.
      Brachial artery flow-mediated dilation (FMD) is widely used in research but
      technical difficulties and problems with calibration between laboratories limit
      its clinical use. Reactive hyperemia-peripheral artery tonometry (RH-PAT,
      EndoPAT) has been developed as a simpler, cheaper, and potentially more
      reproducible method. OBJECTIVES:  We aimed to investigate associations between RH
      PAT and FMD in relation to atherosclerotic risk factor profile. PATIENTS AND
      METHODS:  The study involved 80 subjects (52 men, 28 women) aged 43.6 +/-14.8
      years, with moderate-to-low cardiovascular risk (mean SCORE, 2.2% +/-2%), in whom
      FMD, RH-PAT, and intima-media thickness (IMT) were determined. RESULTS:  The
      reactive hyperemia index (RHI) measured by RH-PAT correlated with FMD (r = 0.35,
      P <0.01). However, no significant correlation was observed between RHI and IMT,
      SCORE, or the number of classical atherosclerotic risk factors (hypertension,
      smoking, diabetes, hypercholesterolemia), while FMD was significantly correlated
      with IMT (r = -0.53, P <0.001), risk factors (r = -0.55, P <0.05), and SCORE (r =
      -0.4, P <0.05). CONCLUSIONS:  Despite its technical requirements, FMD is a more
      sensitive method than RH-PAT in evaluating the effect of classical
      atherosclerotic risk factors on vascular endothelial function. Microvasculature
      response during RH-PAT needs to be further studied, including the assessment of
      nonendothelial factors that may affect the measurements, before RH-PAT becomes
      the universal tool for the evaluation of the endothelial cells.

PMID- 24025638
TI  - Longitudinal relationships between diet-dependent renal acid load and blood
      pressure development in healthy children.
AB  - Diets high in sulfur-rich protein and low in fruits and vegetables affect human
      acid-base balance adversely. Corresponding subclinical forms of metabolic
      acidosis have been linked to hypertension in adults. We longitudinally examined
      relations of dietary acid load with blood pressure in 257 healthy prepuberty
      children with 3 or more parallel 3-day weighed dietary records, 24-h urine, and
      blood pressure measurements. Urinary net acid excretion and the potential renal
      acid load (PRAL), determined as the difference of major urinary nonbicarbonate
      anions and mineral cations, were used to predict dietary acid load. PRAL was also
      calculated from dietary data. In repeated-measures regression analyses, adjusted
      for body size and dietary fiber, an intraindividual increase of 10 mEq above the
      'usual' net acid excretion or urine PRAL were each significantly related to a 0.6
      0.7 mm Hg increased systolic blood pressure. Differences in urine PRAL among the
      children also significantly predicted between-person differences in systolic
      blood pressure. A higher individual net acid excretion or urine PRAL and
      intraindividual increase in urine PRAL were significantly related to higher
      diastolic blood pressure. Blood pressure associations were nonsignificant for
      dietary PRAL and urinary sodium. Thus, in healthy children, renal biomarker
      analyses reveal an association of proton load with higher blood pressure.
      Especially for systolic blood pressure, a more alkalizing nutrition may be
      beneficial for blood pressure development within a given individual. Experimental
      confirmation of a causal acid load-blood pressure link is required. 

PMID- 24025641
TI  - The incidence of biopsy-proven IgA nephropathy is associated with multiple
      socioeconomic deprivation.
AB  - Chronic kidney disease is more common in areas of socioeconomic deprivation, but
      the relationship with the incidence and diagnosis of biopsy-proven renal disease
      is unknown. In order to study this, all consecutive adult patients undergoing
      renal biopsy in West and Central Scotland over an 11-year period were
      prospectively analyzed for demographics, indication, and histologic diagnosis.
      Using the Scottish Index of Multiple Deprivation, 1555 eligible patients were
      separated into quintiles of socioeconomic deprivation according to postcode.
      Patients in the most deprived quintile were significantly more likely to undergo
      biopsy compared with patients from less deprived areas (109.5 compared to 95.9
      per million population/year). Biopsy indications were significantly more likely
      to be nephrotic syndrome, or significant proteinuria without renal impairment.
      Patients in the most deprived quintile were significantly more likely to have
      glomerulonephritis. There was a significant twofold increase in the diagnosis of
      IgA nephropathy in the patients residing in the most compared with the least
      deprived postcodes not explained by the demographics of the underlying
      population. Thus, patients from areas of socioeconomic deprivation in West and
      Central Scotland are significantly more likely to undergo native renal biopsy and
      have a higher prevalence of IgA nephropathy. 

PMID- 24025639
TI  - The urine microRNA profile may help monitor post-transplant renal graft function.
AB  - Noninvasive, cost-effective biomarkers that allow accurate monitoring of graft
      function are needed in kidney transplantation. Since microRNAs (miRNAs) have
      emerged as promising disease biomarkers, we sought to establish an miRNA
      signature in urinary cell pellets comparing kidney transplant patients diagnosed
      with chronic allograft dysfunction (CAD) with interstitial fibrosis and tubular
      atrophy and those recipients with normal graft function. Overall, we evaluated
      191 samples from 125 deceased donor primary kidney transplant recipients in the
      discovery, initial validation, and the longitudinal validation studies for
      noninvasive monitoring of graft function. Of 1733 mature miRNAs studied using
      microarrays, 22 were found to be differentially expressed between groups.
      Ontology and pathway analyses showed inflammation as the principal biological
      function associated with these miRNAs. Twelve selected miRNAs were longitudinally
      evaluated in urine samples of an independent set of 66 patients, at two time
      points after kidney transplant. A subset of these miRNAs was found to be
      differentially expressed between groups early after kidney transplant before
      histological allograft injury was evident. Thus, a panel of urine miRNAs was
      identified as potential biomarkers for monitoring graft function and anticipating
      progression to CAD in kidney transplant patients. 

PMID- 24025640
TI  - Nrf2 suppresses lupus nephritis through inhibition of oxidative injury and the NF
      kappaB-mediated inflammatory response.
AB  - The generation of reactive oxygen species has a pivotal role in both acute and
      chronic glomerular injuries in patients with lupus nephritis. As the
      transcription factor Nrf2 is a major regulator of the antioxidant response and is
      a primary cellular defense mechanism, we sought to determine a role of Nrf2 in
      the progression of lupus nephritis. Pathological analyses of renal biopsies from
      patients with different types of lupus nephritis showed oxidative damage in the
      glomeruli, accompanied by an active Nrf2 antioxidant response. A murine lupus
      nephritis model using Nrf2(+/+) and Nrf2(-/-) mice was established using pristine
      injection. In this model, Nrf2(-/-) mice suffered from greater renal damage and
      had more severe pathological alterations in the kidney. In addition, Nrf2(+/+)
      mice showed ameliorative renal function when treated with sulforaphane, an Nrf2
      inducer. Nrf2(-/-) mice had higher expression of transforming growth factor beta1
      (TGFbeta1), fibronectin, and iNOS. In primary mouse mesangial cells, the
      nephritogenic monoclonal antibody R4A activated the nuclear factor-kappa B (NF
      kappaB) pathway and increased the level of reactive oxygen species, iNOS,
      TGFbeta1, and fibronectin. Knockdown of Nrf2 expression aggravated all
      aforementioned responses induced by R4A. Thus, these results suggest that Nrf2
      improves lupus nephritis by neutralizing reactive oxygen species and by
      negatively regulating the NF-kappaB and TGFbeta1 signaling pathways. 

PMID- 24025642
TI  - Selective deletion of the endothelial sphingosine-1-phosphate 1 receptor
      exacerbates kidney ischemia-reperfusion injury.
AB  - The role for the endothelial sphingosine-1-phosphate 1 receptor (S1P1R) in acute
      kidney injury (AKI) remains unclear as germline endothelial S1P1R deletion is
      embryonically lethal. Here, we generated conditional endothelial S1P1R deficiency
      by crossing mice with floxed S1P1R with mice expressing a tamoxifen-inducible
      form of Cre recombinase under the transcriptional control of the platelet-derived
      growth factor-beta (Pdgfbeta) gene. Mice with tamoxifen-induced deletion of
      endothelial S1P1R had increased renal tubular necrosis, inflammation, and
      impaired vascular permeability, as well as exacerbated renal tubular apoptosis
      after ischemic AKI compared with tamoxifen-treated wild-type mice. Moreover,
      endothelial S1P1R deletion resulted in increased hepatic injury after ischemic
      AKI. As a potential mechanism for exacerbated renal injury, conditional
      endothelial S1P1R-null mice had markedly reduced endothelial HSP27 expression
      compared with wild-type mice. Cultured glomerular endothelial cells treated with
      a specific S1P1R antagonist (W146) for 3 days also showed reduced HSP27
      expression compared with vehicle-treated cells. Finally, mice treated with W146
      for 3 days also showed reduced endothelial HSP27 expression as well as
      exacerbated renal and hepatic injury after ischemic AKI. Thus, our studies
      demonstrate a protective role for endothelial S1P1R against ischemic AKI most
      likely by regulating endothelial barrier integrity and endothelial HSP27
      expression. 

PMID- 24025643
TI  - Lipopolysaccharide-induced cross-tolerance against renal ischemia-reperfusion
      injury is mediated by hypoxia-inducible factor-2alpha-regulated nitric oxide
      production.
AB  - Although the protective effect of lipopolysaccharide (LPS) pretreatment on renal
      ischemia/reperfusion injury is known, a link to hypoxia-inducible factors (HIFs)
      has not been established. Here we show that LPS treatment led to HIF-2alpha
      accumulation in mouse kidneys and endothelial cells, a result of nuclear factor
      kappaB activation. Inactivation of HIF-2alpha, rather than HIF-1alpha, completely
      negated LPS-mediated protection against renal ischemia/reperfusion injury. LPS
      stimulated renoprotection was related to inducible/endothelial nitric oxide
      synthase (iNOS/eNOS) expression, increased production of nitric oxide, and
      enhanced postischemic microcirculatory recovery. All these effects were lost in
      HIF-2alpha knockout mice. Preischemic administration of a nitric oxide donor,
      rather than erythropoietin, restored the lost preconditioning effect of LPS in
      HIF-2alpha knockout mice. In vitro and in vivo studies demonstrated that HIF
      2alpha in endothelial cells, rather than myeloid cells or hepatocytes, was
      responsible for the LPS-mediated effects. Thus, our results demonstrated that LPS
      preconditioning protected against renal ischemia/reperfusion injury by HIF-2alpha
      activation in endothelial cells that subsequently improved renal microvascular
      perfusion and reduced ischemic tubular damage. 

PMID- 24025644
TI  - Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy
      in patients with the APOE Kyoto mutation.
AB  - Lipoprotein glomerulopathy is a rare inherited renal disease, caused by mutation
      of the APOE gene, characterized by proteinuria and nephrotic syndrome with
      elevated serum apoE. Since its treatment and outcome are unknown, we
      retrospectively studied 35 patients within 31 unrelated Han families with biopsy
      proven lipoprotein glomerulopathy residing in the same county in southwest China.
      DNA sequencing detected the APOE Kyoto mutation (p. Arg25Cys) in all patients and
      28 asymptomatic relatives. All shared the same E3 allele. The patients presented
      with proteinuria, higher total triglyceride, and serum apoE levels relative to
      non-carriers. The serum apoE and triglyceride levels of asymptomatic carriers
      were between those of the patients and non-carriers. Sixteen patients received
      fenofibrate treatment for over 12 months. Six reached complete remission
      (proteinuria under 0.3 g/day with stable serum creatinine) with intensive control
      of their lipid profile (normalized serum apoE and triglycerides under 100 mg/dl).
      Eight reached partial remission. At 3 years of follow-up, patients treated with
      fenofibrate had superior survival and stable renal function. Thus, fenofibrate
      can induce lipoprotein glomerulopathy remission and the fibrate effects depend on
      the degree of lipid control and baseline proteinuria. Moreover, normalization of
      serum apoE and triglycerides can be used to judge the efficacy of lipid-lowering
      treatment.

PMID- 24025645
TI  - Early treatment with xenon protects against the cold ischemia associated with
      chronic allograft nephropathy in rats.
AB  - Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with
      functional impairment. Prolonged hypothermic storage-induced ischemia-reperfusion
      injury is associated with the early onset of CAN. As the noble gas xenon is
      clinically used as an anesthetic and has renoprotective properties in a rodent
      model of ischemia-reperfusion injury, we studied whether early treatment with
      xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure
      to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its
      receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell
      proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell
      apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell
      proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1alpha
      individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model,
      xenon exposure of donors before graft retrieval or recipients after engraftment
      enhanced tubular cell proliferation and decreased tubular cell death and cell
      inflammation associated with ischemia-reperfusion injury. Compared with control
      allografts, xenon treatment significantly suppressed T-cell infiltration and
      fibrosis, prevented the development of CAN, and improved renal function. Thus,
      xenon treatment promoted recovery from ischemia-reperfusion injury and reduced
      susceptibility to the subsequent development of CAN in allografts. 

PMID- 24025647
TI  - Volume overload correlates with cardiovascular risk factors in patients with
      chronic kidney disease.
AB  - Volume overload is a predictor of mortality in dialysis patients. However, the
      fluid status of patients with chronic kidney disease (CKD) but not yet on
      dialysis has not been accurately characterized. We used the Body Composition
      Monitor, a multifrequency bioimpedance device, to measure the level of
      overhydration in CKD patients, focusing on the association between overhydration
      and cardiovascular disease risk factors. Overhydration was the difference between
      the amount of extracellular water measured by the Body Composition Monitor and
      the amount of water predicted under healthy euvolemic conditions. Volume overload
      was defined as an overhydration value at and above the 90th percentile for the
      normal population. Of the 338 patients with stages 3-5 CKD, only 48% were
      euvolemic. Patients with volume overload were found to use significantly more
      antihypertensive medications and diuretics but had higher systolic blood
      pressures and an increased arterial stiffness than patients without volume
      overload. In a multivariate analysis, male sex, diabetes, pre-existing
      cardiovascular disease, systolic blood pressure, serum albumin, TNF-alpha, and
      proteinuria were independently all associated with overhydration. Thus, volume
      overload is strongly associated with both traditional and novel risk factors for
      cardiovascular disease. Bioimpedance devices may aid in clinical assessment by
      helping to identify a high-risk group with volume overload among stages 3-5 CKD
      patients. 

PMID- 24025646
TI  - Pharmacological activation of NQO1 increases NAD+ levels and attenuates cisplatin
      mediated acute kidney injury in mice.
AB  - Cisplatin is a widely used chemotherapeutic agent for the treatment of various
      tumors. In addition to its antitumor activity, cisplatin affects normal cells and
      may induce adverse effects, such as ototoxicity, nephrotoxicity, and neuropathy.
      Various mechanisms, such as DNA adduct formation, mitochondrial dysfunction,
      oxidative stress, and inflammatory responses, are critically involved in
      cisplatin-induced adverse effects. As NAD(+) is a cofactor for various enzymes
      associated with cellular homeostasis, we studied the effects of increased NAD(+)
      levels by means of NAD(P)H: quinone oxidoreductase 1 (NQO1) activation using a
      known pharmacological activator (beta-lapachone) in wild-type and NQO1(-/-) mice
      on cisplatin-induced renal dysfunction in vivo. The intracellular NAD(+)/NADH
      ratio in renal tissues was significantly increased in wild-type mice co-treated
      with cisplatin and beta-lapachone compared with the ratio in mice treated with
      cisplatin alone. Inflammatory cytokines and biochemical markers for renal damage
      were significantly attenuated by beta-lapachone co-treatment compared with those
      in the cisplatin alone group. Notably, the protective effects of beta-lapachone
      in wild-type mice were completely abrogated in NQO1(-/-) mice. Moreover, beta
      lapachone enhanced the tumoricidal action of cisplatin in a xenograft tumor
      model. Thus, intracellular regulation of NAD(+) levels through NQO1 activation
      might be a promising therapeutic target for the protection of cisplatin-induced
      acute kidney injury.

PMID- 24025648
TI  - A GHS-consistent approach to health hazard classification of petroleum
      substances, a class of UVCB substances.
AB  - The process streams refined from petroleum crude oil for use in petroleum
      products are among those designated by USEPA as UVCB substances (unknown or
      variable composition, complex reaction products and biological materials). They
      are identified on global chemical inventories with unique Chemical Abstract
      Services (CAS) numbers and names. The chemical complexity of most petroleum
      substances presents challenges when evaluating their hazards and can result in
      differing evaluations due to the varying level of hazardous constituents and
      differences in national chemical control regulations. Global efforts to harmonize
      the identification of chemical hazards are aimed at promoting the use of
      consistent hazard evaluation criteria. This paper discusses a systematic approach
      for the health hazard evaluation of petroleum substances using chemical
      categories and the United Nations (UN) Globally Harmonized System (GHS) of
      classification and labeling. Also described are historical efforts to
      characterize the hazard of these substances and how they led to the development
      of categories, the identification of potentially hazardous constituents which
      should be considered, and a summary of the toxicology of the major petroleum
      product groups. The use of these categories can increase the utility of existing
      data, provide better informed hazard evaluations, and reduce the amount of animal
      testing required. 

PMID- 24025649
TI  - Performance and estimation of the true error rate of classification rules built
      with additional information. An application to a cancer trial.
AB  - Classification rules that incorporate additional information usually present in
      discrimination problems are receiving certain attention during the last years as
      they perform better than the usual rules. Fernandez, M. A., C. Rueda and B.
      Salvador (2006): "Incorporating additional information to normal linear
      discriminant rules," J. Am. Stat. Assoc., 101, 569-577, proved that these rules
      have lower total misclassification probability than the usual Fisher's rule. In
      this paper we consider two issues; on the one hand, we compare these rules with
      those based on shrinkage estimators of the mean proposed by Tong, T., L. Chen and
      H. Zhao (2012): "Improved mean estimation and its application to diagonal
      discriminant analysis," Bioinformatics, 28(4): 531-537. with regard to four
      criteria: total misclassification probability, area under ROC curve, well
      calibratedness and refinement; on the other hand, we consider the estimation of
      the true error rate, which is a very interesting parameter in applications. We
      prove results on the apparent error rate of the rules that expose the need of new
      estimators of their true error rate. We propose four such new estimators. Two of
      them are defined incorporating the additional information into the leave-one-out
      bootstrap. The other two are the corresponding cross-validation after bootstrap
      versions. We compare these estimators with the usual ones in a simulation study
      and in a cancer trial application, showing the good behavior of the rules that
      incorporate additional information and of the new leave-one-out bootstrap
      estimators of their true error rate.

PMID- 24025650
TI  - Inter-observer reliability assessment of the Schatzker, AO/OTA and three-column
      classification of tibial plateau fractures.
AB  - BACKGROUND: The purpose of our study was to evaluate inter-observer reliability
      of the Three-Column classifications with conventional Schatzker and AO/OTA of
      Tibial Plateau Fractures. METHODS: 50 cases involving all kinds of the fracture
      patterns were collected from 278 consecutive patients with tibial plateau
      fractures who were internal fixed in department of Orthopedics and Trauma III in
      Shanghai Sixth People's Hospital. The series were arranged randomly, numbered 1
      to 50. Four observers were chosen to classify these cases. Before the research, a
      classification training session was held to each observer. They were given as
      much time as they required evaluating the radiographs accurately and
      independently. The classification choices made at the first viewing were not
      available during the second viewing. The observers were not provided with any
      feedback after the first viewing. The kappa statistic was used to analyze the
      inter-observer reliability of the three fracture classification made by the four
      observers. RESULTS: The mean kappa values for inter-observer reliability
      regarding Schatzker classification was 0.567 (range: 0.513-0.589), representing
      "moderate agreement". The mean kappa values for inter-observer reliability
      regarding AO/ASIF classification systems was 0.623 (range: 0.510-0.710)
      representing "substantial agreement". The mean kappa values for inter-observer
      reliability regarding Three-Column classification systems was 0.766 (range: 0.706
      0.890), representing "substantial agreement". CONCLUSION: Three-Column
      classification, which is dependent on the understanding of the fractures using CT
      scans as well as the 3D reconstruction can identity the posterior column fracture
      or fragment. It showed "substantial agreement" in the assessment of inter
      observer reliability, higher than the conventional Schatzker and AO/OTA
      classifications. We finally conclude that Three-Column classification provides a
      higher agreement among different surgeons and could be popularized and widely
      practiced in other clinical centers.

PMID- 24025651
TI  - Will another plastic surgeon win a Nobel Prize?

PMID- 24025652
TI  - Predictors of readmission after breast reconstruction: a multi-institutional
      analysis of 5012 patients.
AB  - BACKGROUND: Recent health care legislation institutes penalties for surgical
      readmissions secondary to complications. There is a paucity of evidence
      describing risk factors for readmission after breast reconstruction procedures.
      METHODS: Patients undergoing breast reconstruction in 2011 were identified in the
      National Surgical Quality Improvement Program database. Patients were grouped as
      purely immediate implant/tissue-expander reconstructions or purely autologous
      reconstruction for analysis. Reconstructions involving multiple types of
      procedures were excluded due to difficulty with classification. Perioperative
      variables were analyzed using chi and Student t test as appropriate. Multivariate
      regression modeling was used to identify risk factors for readmission. RESULTS:
      Of 5012 patients meeting inclusion criteria, 3960 and 1052 underwent
      implant/expander and autologous reconstructions, respectively. Implant/expander
      and autologous cohorts experienced similar readmission rates (4.34% vs 5.32%,
      respectively; P = 0.18). However, autologous reconstructions experienced a higher
      rate of overall complications than implant/expander reconstructions (19.96% vs
      5.86%, respectively; P < 0.05), as well as higher rates of reoperation (9.7% vs
      6.5%, respectively; P < 0.05). Common predictors of readmission for
      implant/expander and autologous cohorts included operative time, American Society
      of Anesthesiologist class 3 and 4, and superficial surgical site infection.
      Smoking, sepsis, deep wound infection, organ space infection, and wound
      disruption were predictive of readmission for implant/expander reconstruction
      only, whereas hypertension was predictive of readmission after autologous
      reconstruction only. CONCLUSIONS: This is the first study of readmission rates
      after breast reconstruction. Knowledge of specific risk factors for readmission
      may improve patient outcomes, steer strategies for optimizing reconstructive
      outcomes, and minimize readmissions.

PMID- 24025653
TI  - Surgical management of subungual melanoma: mayo clinic experience of 124 cases.
AB  - BACKGROUND: Optimal surgical management of subungual malignant melanoma (SMM) has
      been debated. METHODS: Our tumor registry was reviewed for surgically treated
      cases of SMM from 1914 to 2010. Resection levels were compared with outcome.
      RESULTS: During a 96-year period, 124 cases of SMM were identified (65 men and 59
      women). Mean age at diagnosis was 58 years. Mean length of symptoms before
      diagnosis was 2.2 years. Lesions occurred on the hand (n = 79) and foot (n = 45).
      The thumb (33.8%) and hallux (25.0%) were affected most. At diagnosis, most had
      local (83.9%) and regional nodal involvement (12.9%). Mean follow-up was 9.4
      years.Mean Breslow depth was 3.1 mm. Amputations were most commonly performed on
      the thumb at the proximal phalanx or metacarpophalangeal joint (43.9%), and on
      the hallux at the proximal phalanx or metatarsophalangeal joint (69.0%).Disease
      progression occurred in 61 (49.2%) patients, and most commonly occurred as
      regional nodal (62.3%) and distant metastasis (42.6%). Disease progression-free
      survival rates at 5, 10, and 15 years were 57.1%, 49.9%, and 47.0%, respectively.
      Fifty-three patients died of melanoma-related causes. Disease-specific survival
      rates at 5, 10, and 15 years after surgery were 59.3%, 49.3%, and 45.2%. Overall
      survival rates at 5, 10, and 15 years were 60.5%, 43.8%, and 33.1%.In 116
      patients who underwent amputation, resection level outcome analysis with
      univariate and multivariate analysis adjusting for tumor depth and clinical
      involvement demonstrated that level of resection was not significantly associated
      with progression-free, overall, or disease-specific survival. CONCLUSIONS:
      Diagnosis of subungual melanoma is often delayed and carries a poor prognosis.
      Conservative resections are warranted as resection level does not influence
      outcome when histologically free margins are obtained. Amputation through the
      proximal phalanx or the metatarsophalangeal joint is required in the hallux and
      toes. Fingers require resection through the distal interphalangeal joint. For the
      thumb, although resection through the interphalangeal joint proved adequate,
      secondary efforts should be directed toward maximizing function and quality of
      life. Function-preserving resections in the thumb with nail removal, partial
      distal phalanx resection, and volar flap reconstruction are easily performed and
      preserve length, maximize joint and sensory function, and improve cosmesis.

PMID- 24025654
TI  - The use of frozen section in the excision of cutaneous malignancy: a Queensland
      experience.
AB  - Frozen section is known to be a valuable tool in the setting of indistinct
      lesions, lesions in cosmetically or functionally important areas, and those with
      recurrent or residual tumors. Most non-Mohs surgery studies comparing frozen
      section with paraffin sections suggest a concordance rate of 85% to 90%, whereas
      studies with Mohs surgery often suggest concordance rates of 95% to 98%. We do
      not perform Mohs surgery at our institutions but feel that the accuracy of frozen
      section is relatively high. Frozen-section data from between 2005 and 2011 was
      analyzed, and a total of 150 cases was found and assessed. Most of the cases were
      basal cell carcinomas and squamous cell carcinomas, with most arising in the head
      and neck region. Half of the resections were for previous incomplete margins with
      the other half being primary excisions. The frozen section was accurate in 97.7%
      of the cases when compared with the formal paraffin sections. However, the
      incomplete rate was higher at 14.8% because of patients with known positive
      margins on frozen section and the use of less accurate techniques of specimen
      analysis. We feel that, when used appropriately, frozen section can be a reliable
      tool and that a negative result should provide the surgeon enough reassurance as
      to undertake immediate reconstruction. 

PMID- 24025656
TI  - 'FAN the SUN brighter': fortifying Africa nutritionally (FAN) - the role of
      public private partnership in scaling up nutrition (SUN) in West Africa.
AB  - The scaling up nutrition (SUN) policy framework requires extensive public-private
      partnership (PPP). Malnutrition is multi-dimensional and should engage multi
      sectoral platforms. The SUN policy however did not fully embrace the dynamics of
      harnessing PPP. The objectives of the present paper are to highlight the reasons
      for the apprehension around PPP and illustrate how effective coordination of PPP
      in West Africa has contributed to implementing large-scale food fortification
      with micronutrients as a complementary nutrition intervention. The experience of
      Helen Keller International (HKI) in scaling up food fortification was emphasised
      with understanding of the factors contributing to indifference by the
      international community to private sector contribution to SUN. The roles of
      different stakeholders in a PPP are elucidated and the process linked to who, why
      and how to engage. The private sector provides direct nutrition services while
      the public sector creates the enabling environment for the private sector to
      thrive on social values. Through this approach fortified vegetable oil and wheat
      flour are now reaching over 70% of the population in West Africa. As a neutral
      broker HKI coordinated and facilitated dialogue among the different stakeholders.
      The core competencies of each stakeholder were harnessed and each partner was
      held accountable. It concludes that multi-sectoral relationship must be
      transparent, equitable and based on shared mutual interests. The rules and values
      of PPP offer opportunities for SUN.

PMID- 24025655
TI  - Overcoming cross-gender differences and challenges in Le Fort-based,
      craniomaxillofacial transplantation with enhanced computer-assisted technology.
AB  - BACKGROUND: Sex-specific anthropometrics, skin texture/adnexae mismatch, and
      social apprehension have prevented cross-gender facial transplantation from
      evolving. However, the scarce donor pool and extreme waitlist times are currently
      suboptimal. Our objective was to (1) perform and assess cadaveric facial
      transplantation for each sex-mismatched scenario using virtual planning with
      cutting guide fabrication and (2) review the advantages/disadvantages of cross
      gender facial transplantation. METHODS: Cross-gender facial transplantation
      feasibility was evaluated through 2 mock, double-jaw, Le Fort-based cadaveric
      allotransplants, including female donor-to-male recipient and male donor-to
      female recipient. Hybrid facial-skeletal relationships were investigated using
      cephalometric measurements, including sellion-nasion-A point and sellion-nasion-B
      point angles, and lower-anterior-facial-height to total-anterior-facial-height
      ratio. Donor and recipient cutting guides were designed with virtual planning
      based on our team's experience in swine dissections and used to optimize the
      results. RESULTS: Skeletal proportions and facial-aesthetic harmony of the
      transplants (n = 2) were found to be equivalent to all reported
      experimental/clinical sex-matched cases by using custom guides and Mimics
      technology. Cephalometric measurements relative to Eastman Normal Values are
      shown. CONCLUSIONS: On the basis of our results, we believe that cross-gender
      facial transplantation can offer equivalent, anatomical skeletal outcomes to
      those of sex-matched pairs using preoperative planning and custom guides for
      execution. Lack of literature discussion of cross-gender facial transplantation
      highlights the general stigmata encompassing the subject. We hypothesize that
      concerns over sex-specific anthropometrics, skin texture/adnexae disparity, and
      increased immunological resistance have prevented full acceptance thus far.
      Advantages include an increased donor pool with expedited reconstruction, as well
      as size-matched donors.

PMID- 24025657
TI  - Ambulatory diagnosis and treatment of nonmalignant pain in the United States,
      2000-2010.
AB  - BACKGROUND: Escalating rates of prescription opioid use and abuse have occurred
      in the context of efforts to improve the treatment of nonmalignant pain.
      OBJECTIVE: The aim of the study was to characterize the diagnosis and management
      of nonmalignant pain in ambulatory, office-based settings in the United States
      between 2000 and 2010. DESIGN, SETTING, AND PARTICIPANTS: Serial cross-sectional
      and multivariate regression analyses of the National Ambulatory Medical Care
      Survey (NAMCS), a nationally representative audit of office-based physician
      visits, were conducted. MEASURES: (1) Annual visit volume among adults with
      primary pain symptom or diagnosis; (2) receipt of any pain treatment; and (3)
      receipt of prescription opioid or nonopioid pharmacologic therapy in visits for
      new musculoskeletal pain. RESULTS: Primary symptoms or diagnoses of pain
      consistently represented one-fifth of visits, varying little from 2000 to 2010.
      Among all pain visits, opioid prescribing nearly doubled from 11.3% to 19.6%,
      whereas nonopioid analgesic prescribing remained unchanged (26%-29% of visits).
      One-half of new musculoskeletal pain visits resulted in pharmacologic treatment,
      although the prescribing of nonopioid pharmacotherapies decreased from 38% of
      visits (2000) to 29% of visits (2010). After adjusting for potentially
      confounding covariates, few patient, physician, or practice characteristics were
      associated with a prescription opioid rather than a nonopioid analgesic for new
      musculoskeletal pain, and increases in opioid prescribing generally occurred
      nonselectively over time. CONCLUSIONS: Increased opioid prescribing has not been
      accompanied by similar increases in nonopioid analgesics or the proportion of
      ambulatory pain patients receiving pharmacologic treatment. Clinical alternatives
      to prescription opioids may be underutilized as a means of treating ambulatory
      nonmalignant pain.

PMID- 24025658
TI  - Medicare Part D plan generosity and medication use among dual-eligible nursing
      home residents.
AB  - BACKGROUND: In 2006, dual-eligible nursing home residents were randomly assigned
      to a Medicare Part D prescription drug plan (PDP). Subsequently, residents not
      enrolled in qualified plans at the start of the next year were rerandomized. PDPs
      vary in generosity through differences in medication coverage and utilization
      management. Therefore, residents' assigned plans may be relatively more or less
      generous for their particular drugs. The impact of generosity on residents'
      medication use and health outcomes is unknown. METHODS: Using data from 2005 to
      2008, we estimated logistic regression models of the impact of coverage and
      utilization management on the risk for medication changes and gaps in use,
      hospitalizations, and death among elderly nursing home residents using 1 of 6
      selected drug classes, adjusting for patient characteristics. RESULTS: Few
      current medication users faced noncoverage of their drug (0.4% to 8.7%) or prior
      authorization or step therapy requirements if the drug was covered (1.1% to
      37.4%). After adjusting for individual-level covariates, residents with
      noncovered drugs were more likely than residents with covered drugs to change
      medications in most classes studied (eg, for 2006 angiotensin receptor blocker
      users, the adjusted average probability of medication change was 0.35 when
      uncovered vs. 0.11 when covered). Those subjected to prior authorization or step
      therapy were more likely to change in a subset of classes. There were no
      statistically significant differences in the rates of hospitalization or death
      after correcting for multiple comparisons. CONCLUSIONS: The Part D benefit's
      special protections for nursing home residents may have ameliorated the health
      impact of coverage limits on this frail elderly population.

PMID- 24025659
TI  - Application of constraint-induced movement therapy in clinical practice: an
      online survey.
AB  - OBJECTIVE: To investigate current knowledge and application in practice of
      constraint-induced movement therapy (CIMT) by therapists within the United
      Kingdom. DESIGN: An online 19-item survey. SETTING: Neurological rehabilitation.
      PARTICIPANTS: Occupational therapists and physiotherapists (N=489) currently
      working or within 3 months of working with the adult acquired brain injury
      population were recruited from 2 specialist interest groups. INTERVENTIONS:
      Database administrators of 2 specialist interest groups circulated an e-mail to
      all therapists on the database to invite them to complete the online survey. MAIN
      OUTCOME MEASURES: Not applicable. RESULTS: Most therapists (62.9%, n=306) had not
      used CIMT. Those who had used it were only using 2 or 3 components of the core 7
      component CIMT protocol. Therapists identified 2 main barriers to the
      implementation of CIMT: lack of resources (staffing; 20.7%, n=63) and lack of
      training (20%, n=61). CONCLUSIONS: Adoption into practice remains limited.
      Despite a significant evidence base in support of CIMT, most therapists are not
      using CIMT in practice. This article indicates how concerns and barriers related
      to CIMT may be minimized to translate this robust intervention from research into
      clinical practice.

PMID- 24025660
TI  - Universal frozen spectra after time-dependent symmetry restoring phase
      transitions.
AB  - For a general O(N) model, we study the time-dependent phase transition from a
      state with broken symmetry <phi> ? 0 to the symmetric phase <phi> = 0. During
      this non-equilibrium process, the primordial quantum (or thermal) fluctuations of
      the initial Goldstone modes are frozen and result in a deviation from the final
      ground (or thermal) state. For very slow transitions, we find that these
      fluctuations display a universal scaling behaviour. Their spectra are universal
      functions of a single parameter, which combines the initial frequency of the
      Goldstone modes and the sweep rate. As a result, the final two-point function
      [phia(r)phib(r')] is not exponentially suppressed at large distances Deltar = r -
      r' (as it would be in the ground state) but decays polynomially in 1/|Deltar|.
      Finally, we exemplify this universal behaviour for the transition from the super
      fluid phase to the Mott state in the Bose-Hubbard model.

PMID- 24025661
TI  - Valuing SF-6D Health States Using a Discrete Choice Experiment.
AB  - BACKGROUND: SF-6D utility weights are conventionally produced using a standard
      gamble (SG). SG-derived weights consistently demonstrate a floor effect not
      observed with other elicitation techniques. Recent advances in discrete choice
      methods have allowed estimation of utility weights. The objective was to produce
      Australian utility weights for the SF-6D and to explore the application of
      discrete choice experiment (DCE) methods in this context. We hypothesized that
      weights derived using this method would reflect the largely monotonic
      construction of the SF-6D. METHODS: We designed an online DCE and administered it
      to an Australia-representative online panel (n = 1017). A range of specifications
      investigating nonlinear preferences with respect to additional life expectancy
      were estimated using a random-effects probit model. The preferred model was then
      used to estimate a preference index such that full health and death were valued
      at 1 and 0, respectively, to provide an algorithm for Australian cost-utility
      analyses. RESULTS: Physical functioning, pain, mental health, and vitality were
      the largest drivers of utility weights. Combining levels to remove illogical
      orderings did not lead to a poorer model fit. Relative to international SG
      derived weights, the range of utility weights was larger with 5% of health states
      valued below zero. CONCLUSION: s. DCEs can be used to investigate preferences for
      health profiles and to estimate utility weights for multi-attribute utility
      instruments. Australian cost-utility analyses can now use domestic SF-6D weights.
      The comparability of DCE results to those using other elicitation methods for
      estimating utility weights for quality-adjusted life-year calculations should be
      further investigated.

PMID- 24025663
TI  - PET-based dose delivery verification in proton therapy: a GATE based simulation
      study of five PET system designs in clinical conditions.
AB  - PET is a promising technique for in vivo treatment verification in hadrontherapy.
      Three main PET geometries dedicated to in-beam treatment monitoring have been
      proposed in the literature: the dual-head PET geometry, the OpenPET geometry and
      the slanted-closed ring geometry. The aim of this work is to characterize the
      performance of two of these dedicated PET detectors in realistic clinical
      conditions. Several configurations of the dual-head PET and OpenPET systems were
      simulated using GATE v6.2. For the dual-head configuration, two aperture angles
      (15 degrees  and 45 degrees ) were studied. For the OpenPET system, two gaps
      between rings were investigated (110 and 160 mm). A full-ring PET system was also
      simulated as a reference. After preliminary evaluation of the sensitivity and
      spatial resolution using a Derenzo phantom, a real small-field head and neck
      treatment plan was simulated, with and without introducing patient displacements.
      No wash-out was taken into account. 3D maps of the annihilation photon locations
      were deduced from the PET data acquired right after the treatment session (5 min
      acquisition) using a dedicated OS-EM reconstruction algorithm. Detection
      sensitivity at the center of the field-of-view (FOV) varied from 5.2% (45 degrees
      dual-head system) to 7.0% (full-ring PET). The dual-head systems had a more
      uniform efficiency within the FOV than the OpenPET systems. The spatial
      resolution strongly depended on the location within the FOV for the phi = 45
      degrees  dual-head system and for the two OpenPET systems. All investigated
      architectures identified the magnitude of mispositioning introduced in the
      simulations within a 1.5 mm accuracy. The variability on the estimated
      mispositionings was less than 2 mm for all PET systems. 

PMID- 24025662
TI  - A comparison of direct and indirect methods for the estimation of health
      utilities from clinical outcomes.
AB  - BACKGROUND: Analysts frequently estimate health state utility values from other
      outcomes. Utility values like EQ-5D have characteristics that make standard
      statistical methods inappropriate. We have developed a bespoke, mixture model
      approach to directly estimate EQ-5D. An indirect method, "response mapping,"
      first estimates the level on each of the 5 dimensions of the EQ-5D and then
      calculates the expected tariff score. These methods have never previously been
      compared. METHODS: We use a large observational database from patients with
      rheumatoid arthritis (N = 100,398). Direct estimation of UK EQ-5D scores as a
      function of the Health Assessment Questionnaire (HAQ), pain, and age was
      performed with a limited dependent variable mixture model. Indirect modeling was
      undertaken with a set of generalized ordered probit models with expected tariff
      scores calculated mathematically. Linear regression was reported for comparison
      purposes. Impact on cost-effectiveness was demonstrated with an existing model.
      RESULTS: The linear model fits poorly, particularly at the extremes of the
      distribution. The bespoke mixture model and the indirect approaches improve fit
      over the entire range of EQ-5D. Mean average error is 10% and 5% lower compared
      with the linear model, respectively. Root mean squared error is 3% and 2% lower.
      The mixture model demonstrates superior performance to the indirect method across
      almost the entire range of pain and HAQ. These lead to differences in cost
      effectiveness of up to 20%. CONCLUSIONS: There are limited data from patients in
      the most severe HAQ health states. Modeling of EQ-5D from clinical measures is
      best performed directly using the bespoke mixture model. This substantially
      outperforms the indirect method in this example. Linear models are inappropriate,
      suffer from systematic bias, and generate values outside the feasible range.

PMID- 24025665
TI  - The effect of municipality characteristics on disability retirement.
AB  - OBJECTIVES: In addition to individual-level characteristics also contextual
      factors may contribute to the large regional variation seen in disability
      retirement. We examined the associations of municipality-level characteristics
      and disability retirement due to all causes, musculoskeletal diseases, mental
      disorders and other diseases. METHODS: A register-based study was conducted with
      a 20% random sample of the Finnish population aged 25-62 years. Municipalities
      were separately divided into quintiles by their proportion of manual workers,
      unemployed and industrial employees. Multilevel Poisson regression analysis was
      applied to examine associations between the three municipality characteristics
      and disability retirement during a 5-year follow-up. RESULTS: All three
      municipality-level indicators were associated with disability retirement, but the
      association between the proportion of industrial workers and disability
      retirement disappeared after adjustment for age, gender, marital status,
      socioeconomic position, unemployment and industrial employee status at the
      individual level. The associations were particularly strong for disability
      retirement due to musculoskeletal diseases: in the municipalities with the
      highest proportion of manual workers, the risk for disability retirement due to
      musculoskeletal diseases was 2.5 times higher than in the municipalities with
      least manual workers. After adjustment for the individual-level factors, the risk
      was 1.5 times higher. Cross-level interactions showed that the risk of disability
      retirement increased with the increasing proportion of unemployment in the
      municipality only among those who had not experienced unemployment themselves.
      CONCLUSIONS: Municipality-level characteristics made an independent contribution
      to the probability of disability retirement in particular due to musculoskeletal
      diseases. Also, area-level characteristics should be considered when targeting
      disability retirement.

PMID- 24025664
TI  - Trends and risk groups for smoking during pregnancy in Finland and other Nordic
      countries.
AB  - BACKGROUND: Reductions in maternal smoking can prevent pregnancy complications
      and adverse effects to foetus. Our objective was to study how the prevalence of
      maternal smoking differs between Nordic countries, and to identify target groups
      for smoking-cessation interventions. METHODS: Information on maternal smoking and
      background factors was requested from the Nordic countries (the Danish National
      Board of Health, the Finnish National Institute for Health and Welfare, the
      Public Health Institute in Iceland, the Norwegian Institute of Public Health and
      the Swedish National Board of Health and Welfare). Data on maternal smoking were
      received from 1991 to 2010 in Denmark, 1987 to 2010 in Finland, 1999 to 2009 in
      Norway and 1983 to 2008 in Sweden. Trends in smoking were studied by using test
      for relative proportion. RESULTS: The prevalence of maternal smoking in early
      pregnancy has declined in the countries during the past 20 years (Denmark: from
      30.6 to 12.5%; Norway: 20.6 to 16.5% and Sweden: 31.4 to 6.9%), except in Finland
      (a steady prevalence at 15%). The highest rates of smoking in early pregnancy
      were among teenagers (24% in Sweden and 49% in Finland and Norway). Single women
      were 2-3 times more likely to smoke than married women. The women in the lowest
      socioeconomic group were 6-7 times more likely to smoke than women in the highest
      group in Finland and Norway. CONCLUSION: Maternal smoking and its trends differed
      between the Nordic countries. The highest smoking rates during pregnancy were
      observed among teenagers, single women and women with a low socioeconomic
      position.

PMID- 24025666
TI  - Arterial stiffness determined according to the cardio-ankle vascular index(CAVI)
      is associated with mild cognitive decline in community-dwelling elderly subjects.
AB  - AIMS: The purpose of this study was to determine the cross-sectional relationship
      between the cognitive function and cardio-ankle vascular index(CAVI) in Japanese
      community-dwelling elderly subjects. METHODS: A total of 179 Japanese community
      dwelling elderly subjects were recruited for this study. The age, height, weight,
      gender and past medical history(cardiovascular disease, hypertension, diabetes
      mellitus, hyperlipidemia) of each participant was recorded. In addition, the
      degree of arterial stiffness was determined according to the CAVI, while the
      cognitive function was assessed using the Mini-Mental State Examination(MMSE).
      After dividing the cohort into two groups according to the MMSE score(<=26, >26),
      we used a multiple regression analysis to assign the level of the cognitive
      function as a dependent variable. RESULTS: The data were statistically analyzed
      for the 174 participants(84 men and 90 women) who completed the data collection
      process without omissions. A multivariate logistic regression analysis showed
      that a higher weight(Odds Ratio [OR]: 1.05, 95% Confidence Interval [95% CI]:
      1.00- 1.11, p=0.03), male gender(OR: 3.13, 95% CI: 1.05-9.34, p=0.04) and lower
      CAVI(OR: 0.68, 95% CI: 0.48-0.96, p=0.03) were significantly correlated with a
      higher MMSE score. We also found significant correlations between the MMSE and
      weight(OR: 1.11, 95% CI: 1.03-1.19, p=0.01) and CAVI(OR: 0.57, 95% CI: 0.33-0.98,
      p=0.04) in elderly men only using a gender-specific analysis. CONCLUSIONS: We
      found that the elderly subjects with a high CAVI exhibited a worse cognitive
      function even after adjusting for age, height, weight and gender. This finding
      therefore indicates the usefulness of the CAVI in the early detection of
      dementia.

PMID- 24025667
TI  - Challenges in biobank governance in Sub-Saharan Africa.
AB  - BACKGROUND: Biological sample and data transfer within and out of Africa is
      steeped in controversy With the H3Africa project now aiming to establish biobanks
      in Africa, it is essential that there are ethical and legal governance structures
      in place to oversee the operation of these biobanks. Such governance is essential
      to ensuring that donors are protected, that cultural perspectives are respected
      and that researchers have a ready availability of ethically sourced biological
      samples. METHODS: A literature review of all legislation, regulations, guidelines
      and standard operating procedures on informed consent, confidentiality and the
      transfer of biological samples amongst countries in Sub-Saharan Africa was
      conducted. In addition, an examination of the websites of departments of health
      and national ethics committees was performed. Researchers and research ethics
      scholars in the field in various African countries were contacted for assistance.
      A literature review of all studies examining participants views on issues related
      to biobanking in Africa was carried out and five separate studies were found.
      RESULTS: It was found that biobanking guidelines differ substantially across Sub
      Saharan Africa regarding biobanking and often conflicted across borders. This has
      the potential to negatively impact collaboration. Furthermore, the guidelines in
      place often do not recognise the ethical difficulties arising from the transfer
      of biological samples and are unsuitable to regulate biobanks. Additionally,
      there is insufficient research into the views of research participants and
      stakeholders on the use of biological /samples. CONCLUSION: Collaboration is
      necessary to ensure the success of biobanking projects in Africa. To achieve
      this, there should be some harmonization of guidelines across Africa which would
      aid in transferring biological samples across borders. These guidelines should
      reflect the unique ethical issues arising out of the storage and secondary uses
      of biological samples. Finally, further research into the views of research
      participants is necessary. Such studies should aid in the drafting of any new
      harmonization guidelines.

PMID- 24025668
TI  - Algorithm for pre-emptive glycopeptide treatment in patients with haematologic
      malignancies and an Enterococcus faecium bloodstream infection.
AB  - INTRODUCTION: Nowadays Enterococcus faecium has become one of the most emerging
      and challenging nosocomial pathogens. The aim of this study was to determine risk
      factors in haematology patients who are at risk of an Enterococcus faecium
      bloodstream infection (BSI) and should be considered for pre-emptive glycopeptide
      treatment. With these identified risk factors a prediction model can be developed
      for clinical use. METHODS: Retrospectively clinical and microbiological data in
      33 patients with an E. faecium BSI were compared to 66 control patients during a
      5-year period at the haematology ward. Multivariate logistic regression was used
      to explore the independent risk factors and a prediction model was developed to
      determine the risk of an E. faecium BSI. RESULTS: E. faecium BSIs were found to
      be associated with high mortality rates. Independent risk factors for E. faecium
      BSI were colonization with E. faecium 30 days prior to blood culture (OR 5.71; CI
      1.7-18.7), combination of neutropenia and abdominal focus (4.37; 1.4-13.4), age >
      58 years (4.01; 1.3-12.5), hospital stay prior to blood culture > 14 days (3.55;
      0.98-12.9) and CRP (C-reactive protein) level >125 mg/L (4.37; 1.1-10.2).
      CONCLUSION: Using data from this study, risk stratification for the development
      of an E. faecium BSI in patients with haematological malignancies is possible.
      Pre-emptive treatment should be considered in those patients who are at high
      risk. Using a prediction model as designed in this study, antibiotic stewardship
      in terms of prudent use of glycopeptides can be improved and might be helpful in
      controlling further spread of VRE (vancomycin resistant enterococci).

PMID- 24025669
TI  - The relationship between mixed microbial culture composition and PHA production
      performance from fermented molasses.
AB  - Polyhydroxyalkanoates (PHAs) are polyesters that can be produced from industrial
      wastewater or surplus products by mixed microbial cultures (MMC). To optimise PHA
      production by MMCs, the link between the microbial structure and function of
      these enrichments must be better established. This study investigates, for the
      first time, the impact of operational changes on the microbial community and the
      associated process performance of PHA producing MMCs. It was found that a PHA
      producing community fed with fermented molasses was dominated by a combination of
      Azoarcus, Thauera and Paracoccus, where the former two groups were present in
      highest abundance. Dominance of either Thauera or Azoarcus seemed to be
      determined by the organic loading rate imposed in the selection reactor. While
      higher Azoarcus enrichments led to higher PHA production yields and lower biomass
      growth yields as compared to Thauera, the Thauera abundance was strongly linked
      to higher hydroxyvalerate (HV) fractions. Paracoccus abundance was correlated
      with a lower PHA production capacity as compared to Azoarcus, and produced lower
      HV fractions than Thauera and Azoarcus. The findings of this study suggest that
      MMCs targeting the enrichment of Azoarcus as the primary biomass fraction with
      Thauera as a minor fraction lead to optimal specific PHA production and polymers
      with high HV content, which is likely to improve their mechanical properties. 

PMID- 24025670
TI  - The effect of family sex composition on fertility desires and family planning
      behaviors in urban Uttar Pradesh, India.
AB  - BACKGROUND: A cultural preference for sons has been well documented in India,
      resulting in skewed sex ratios, especially exhibited in northwest India. Previous
      research has shown that family sex composition is associated with family planning
      (FP) use and couples' desire for more children. This study examines family sex
      composition and fertility and FP behaviors in urban Uttar Pradesh, India; little
      work has examined these issues in urban settings where family sizes are smaller
      and FP use is common. METHODS: Data for this analysis comes from a 2010
      representative survey of married, non-pregnant fecund women aged 15-49 from six
      cities in Uttar Pradesh, India. Multivariate analyses are used to examine the
      association between family sex composition and fertility desires and FP use.
      RESULTS: The multivariate results indicate that family sex composition is
      associated with fertility desires and FP use. Women without living children and
      without at least one child of each sex are significantly less likely to want no
      more children and women with both sons and daughters but more sons are
      significantly more likely to want no more children as compared to women that have
      both sons and daughters but more daughters. Women with no living children and
      women with daughters but no sons are less likely to be modern FP users than
      nonusers whereas women with both sons and daughters but more sons are more likely
      to be modern FP users than nonusers as compared to women with both sons and
      daughters but more daughters. CONCLUSIONS: These findings confirm that family sex
      composition affects fertility behavior and also reveals that preference for sons
      persists in urban Uttar Pradesh. These results underscore the importance of
      programs and policies that work to enhance the value of girl children.

PMID- 24025671
TI  - Spectroscopic and biological activities studies of bivalent transition metal
      complexes of Schiff bases derived from condensation of 1,4-phenylenediamine and
      benzopyrone derivatives.
AB  - Many tools of analysis such as elemental analyses, infrared, ultraviolet-visible,
      electron spin resonance (ESR) and thermal analysis, as well as conductivity and
      magnetic susceptibility measurements were used to elucidate the structures of the
      newly prepared Co(II), Ni(II) and Cu(II) complexes with Schiff bases derived from
      the condensation of 1,4-phenylenediamine with 6-formyl-7-hydroxy-5-methoxy-2
      methylbenzo-pyran-4-one (H2L) or 5,7-dihydroxy-6-formyl-2-methylbenzopyran-4-one
      (H4L). The data showed that all formed complexes are 1:1 or 2:2 (M:L) and non
      electrolyte chelates. The Co(II) and Cu(II) complexes of the two Schiff bases
      were screened for antibacterial activities by the disk diffusion method. The
      antibacterial activity was screened using Escherichia coli and Staphylococcus
      capitis but the antifungal activity was examined by using Aspergillus flavus and
      Candida albicans. The Results showed that the tested complexes have
      antibacterial, except CuH4L, but not antifungal activities.

PMID- 24025673
TI  - The midline-based nasolabial transposition (MNT) flap: an original single-stage
      technique for nasal tip reconstruction.
AB  - BACKGROUND: Nasolabial flaps based on the lateral side of the nose for the
      reconstruction of lateral nasal defects in a single-stage procedure have been
      described. Similarly, in midline defects, nasolabial flaps can be used but a 2
      stage procedure is classically required. The Midline-based Nasolabial
      Transposition (MNT) flap is presented as a new single-stage procedure for nasal
      tip reconstruction. MATERIALS AND METHODS: Between 2009 and 2011, an MNT flap was
      used as a single-stage procedure in 3 cases of large nasal defects of the tip
      where the forehead flap was either contraindicated or rejected as an option by
      the patient. RESULTS: There were no complications and a satisfactory aesthetic
      result was achieved in all cases. CONCLUSIONS: The MNT flap is a new single-stage
      procedure for large nasal tip defects and as such represents an interesting
      alternative to the classical 2-stage forehead and nasolabial flaps, especially in
      elderly patients.

PMID- 24025672
TI  - Plasmodium falciparum ATG8 implicated in both autophagy and apicoplast formation.
AB  - Amino acid utilization is important for the growth of the erythrocytic stages of
      the human malaria parasite Plasmodium falciparum, however the molecular mechanism
      that permits survival of the parasite during conditions of limiting amino acid
      supply is poorly understood. We provide data here suggesting that an autophagy
      pathway functions in P. falciparum despite the absence of a typical lysosome for
      digestion of the autophagosomes. It involves PfATG8, which has a C-terminal
      glycine which is absolutely required for association of the protein with
      autophagosomes. Amino acid starvation provoked increased colocalization between
      PfATG8- and PfRAB7-labeled vesicles and acidification of the colabeled structures
      consistent with PfRAB7-mediated maturation of PfATG8-positive autophagosomes;
      this is a rapid process facilitating parasite survival. Immuno-electron
      microscopic analyses detected PfRAB7 and PfATG8 on double-membrane-bound vesicles
      and also near or within the parasite's food vacuole, consistent with
      autophagosomes fusing with the endosomal system before being routed to the food
      vacuole for digestion. In nonstarved parasites, PfATG8, but not PfRAB7, was found
      on the intact apicoplast membrane and on apicoplast-targeted vesicles and
      apicoplast remnants when the formation of the organelle was disrupted; a
      localization also requiring the C-terminal glycine. These findings suggest that
      in addition to a classical role in autophagy, which involves the PfRAB7-endosomal
      system and food vacuole, PfATG8 is associated with apicoplast-targeted vesicles
      and the mature apicoplast, and as such contributes to apicoplast formation and
      maintenance. Thus, PfATG8 may be unique in having such a second role in addition
      to the formation of autophagosomes required for classical autophagy. 

PMID- 24025675
TI  - Molecular basis for homo-dimerization of the CIDE domain revealed by the crystal
      structure of the CIDE-N domain of FSP27.
AB  - FSP27 (CIDE-3 in humans) plays critical roles in lipid metabolism and apoptosis
      and is known to be involved in regulation of lipid droplet (LD) size and lipid
      storage and apoptotic DNA fragmentation. Given that CIDE-containing proteins
      including FSP27 are associated with many human diseases including cancer, aging,
      diabetes, and obesity, studies of FSP27 and other CIDE-containing proteins are of
      great biological importance. As a first step toward elucidating the molecular
      mechanisms of FSP27-mediated lipid droplet growth and apoptosis, we report the
      crystal structure of the CIDE-N domain of FSP27 at a resolution of 2.0 A. The
      structure revealed a possible biologically important homo-dimeric interface
      similar to that formed by the hetero-dimeric complex, CAD/ICAD. Comparison with
      other structural homologues revealed that the PB1 domain of BEM1P, ubiquitin-like
      domain of BAG6 and ubiquitin are structurally similar proteins. Our homo-dimeric
      structure of the CIDE-N domain of FSP27 will provide important information that
      will enable better understanding of the function of FSP27.

PMID- 24025674
TI  - Transient light-induced intracellular oxidation revealed by redox biosensor.
AB  - We have implemented a ratiometric, genetically encoded redox-sensitive green
      fluorescent protein fused to human glutaredoxin (Grx1-roGFP2) to monitor real
      time intracellular glutathione redox potentials of mammalian cells. This probe
      enabled detection of media-dependent oxidation of the cytosol triggered by short
      wavelength excitation. The transient nature of light-induced oxidation was
      revealed by time-lapse live cell imaging when time intervals of less than 30s
      were implemented. In contrast, transient ROS generation was not observed with the
      parental roGFP2 probe without Grx1, which exhibits slower thiol-disulfide
      exchange. These data demonstrate that the enhanced sensitivity of the Grx1-roGFP2
      fusion protein enables the detection of short-lived ROS in living cells. The
      superior sensitivity of Grx1-roGFP2, however, also enhances responsiveness to
      environmental cues introducing a greater likelihood of false positive results
      during image acquisition.

PMID- 24025676
TI  - Four products from Escherichia coli pseudogenes increase hydrogen production.
AB  - Pseudogenes are considered to be nonfunctional genes that lack a physiological
      role. By screening 3985 Escherichia coli mutants using chemochromic membranes, we
      found four pseudogenes involved in hydrogen metabolism. Knockouts of pseudogenes
      ydfW and ypdJ had a defective hydrogen phenotype on glucose and formate,
      respectively. Also, the knockout of pseudogene yqiG formed hydrogen from formate
      but not from glucose. For the yqiG mutant, 100% hydrogen recovery was obtained by
      the complementation of YqiG via a plasmid. The knockout of pseudogene ylcE showed
      hydrogen deficiency in minimal media which suggested that the role of YlcE is
      associated with cell growth. Hence, the products of these four pseudogenes play
      an important physiological role in hydrogen production in E. coli.

PMID- 24025677
TI  - Identification of 6-octadecynoic acid from a methanol extract of Marrubium
      vulgare L. as a peroxisome proliferator-activated receptor gamma agonist.
AB  - 6-Octadecynoic acid (6-ODA), a fatty acid with a triple bond, was identified in
      the methanol extract of Marrubium vulgare L. as an agonist of peroxisome
      proliferator-activated receptor gamma (PPARgamma). Fibrogenesis caused by hepatic
      stellate cells is inhibited by PPARgamma whose ligands are clinically used for
      the treatment of diabetes. Plant extracts of Marrubium vulgare L., were screened
      for activity to inhibit fibrosis in the hepatic stellate cell line HSC-T6 using
      Oil Red-O staining, which detects lipids that typically accumulate in quiescent
      hepatic stellate cells. A methanol extract with activity to stimulate
      accumulation of lipids was obtained. This extract was found to have PPARgamma
      agonist activity using a luciferase reporter assay. After purification using
      several chromatographic methods, 6-ODA, a fatty acid with a triple bond, was
      identified as a candidate of PPARgamma agonist. Synthesized 6-ODA and its
      derivative 9-octadecynoic acid (9-ODA), which both have a triple bond but in
      different positions, activated PPARgamma in a luciferase reporter assay and
      increased lipid accumulation in 3T3-L1 adipocytes in a PPARgamma-dependent
      manner. There is little information about the biological activity of fatty acids
      with a triple bond, and to our knowledge, this is the first report that 6-ODA and
      9-ODA function as PPARgamma agonists.

PMID- 24025678
TI  - Cellular aging is associated with increased ubiquitylation of histone H2B in
      yeast telomeric heterochromatin.
AB  - Epigenetic changes in chromatin state are associated with aging. Notably, two
      histone modifications have recently been implicated in lifespan regulation,
      namely acetylation at H4 lysine 16 in yeast and methylation at H3 lysine 4 (H3K4)
      in nematodes. However, less is known about other histone modifications. Here, we
      report that cellular aging is associated with increased ubiquitylation of histone
      H2B in yeast telomeric heterochromatin. An increase in ubiquitylation at histone
      H2B lysine 123 and methylations at both H3K4 and H3 lysine 79 (H3K79) was
      observed at the telomere-proximal regions of replicatively aged cells, coincident
      with decreased Sir2 abundance. Moreover, deficiencies in the H2B ubiquitylase
      complex Rad6/Bre1 as well as the deubiquitylase Ubp10 reduced the lifespan by
      altering both H3K4 and H3K79 methylation and Sir2 recruitment. Thus, these
      results show that low levels of H2B ubiquitylation are a prerequisite for a
      normal lifespan and the trans-tail regulation of histone modifications regulates
      age-associated Sir2 recruitment through telomeric silencing.

PMID- 24025679
TI  - In silico analysis of stomach lineage specific gene set expression pattern in
      gastric cancer.
AB  - Stomach lineage specific gene products act as a protective barrier in the normal
      stomach and their expression maintains the normal physiological processes,
      cellular integrity and morphology of the gastric wall. However, the regulation of
      stomach lineage specific genes in gastric cancer (GC) is far less clear. In the
      present study, we sought to investigate the role and regulation of stomach
      lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the
      mRNA expression profiles of normal stomach tissue with other organ tissue. The
      obtained SLSGS was found to be under expressed in gastric tumors. Functional
      annotation analysis revealed that the SLSGS was enriched for digestive function
      and gastric epithelial maintenance. Employing a single sample prediction method
      across GC mRNA expression profiles identified the under expression of SLSGS in
      proliferative type and invasive type gastric tumors compared to the metabolic
      type gastric tumors. Integrative pathway activation prediction analysis revealed
      a close association between estrogen-alpha signaling and SLSGS expression pattern
      in GC. Elevated expression of SLSGS in GC is associated with an overall increase
      in the survival of GC patients. In conclusion, our results highlight that
      estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor
      of metabolic type GC and prognostic factor in GC.

PMID- 24025680
TI  - Regulation of neuropeptide Y Y1 receptor expression by bone morphogenetic protein
      2 in C2C12 myoblasts.
AB  - The neuropeptide Y (NPY) system is known as one of the major neural signaling
      pathways. NPY, produced by peripheral tissues including osteoblasts, is known to
      bind to the Y1 receptor. Recently, osteoblast-specific Y1 receptor knockout mice
      were developed and were found to have a high bone mass phenotype, indicating a
      role for the NPY-Y1 receptor axis as a regulator of bone homeostasis. However,
      regulation of Y1 receptor expression during osteoblastic differentiation remains
      unexplored. In the present study, we examined the role of bone morphogenetic
      protein (BMP) 2 signaling in regulating Y1 receptor expression. In C2C12 cells,
      expression of Y1 receptor mRNA was induced by BMP2. This induction was also
      observed after co-transfection with Smad1 and Smad4, the intracellular signaling
      molecules of the BMP2 signaling pathway. In a transfection assay, Smad1/4 up
      regulated transcriptional activity through interaction with the Y1 receptor gene
      promoter. Following transfection of MC3T3-E1 cells with siRNA for the Y1
      receptor, the expression of alkaline phosphatase, osteocalcin, Runx2 and osterix
      were increased. These results show that BMP2 signaling regulates Y1 receptor gene
      expression, and raises the possibility that NPY acts in osteoblasts via an
      autocrine mechanism.

PMID- 24025681
TI  - Nrg1 functions as a global transcriptional repressor of glucose-repressed genes
      through its direct binding to the specific promoter regions.
AB  - Nrg1 is a zinc finger protein involved in the glucose repression of several
      glucose-repressed genes such as STA1, SUC2, and GAL1. Although the molecular
      details of the Nrg1-mediated repression of STA1 have been partly characterized,
      it still remains largely unknown how Nrg1 regulates these multiple target genes.
      In this study, we show that Nrg1 mediates the glucose repression of SUC2 and HXT2
      through its direct binding to the specific promoter regions; it binds to the -404
      to -360 region of the SUC2 promoter and the -957 to -810 region of the HXT2
      promoter. Nrg1 also interacts with the -380 to -250 region of the PCK1 promoter,
      suggesting that it might also contribute to the PCK1 repression. In addition,
      ChIP assays confirmed that Nrg1 associated with specific promoter regions of
      these glucose-repressed genes in vivo. Analysis of the DNA fragments to which it
      binds indicates that Nrg1 may recognize T/ACCCC sequence within the promoters of
      these glucose-repressed genes as well as in its own promoter. Collectively, our
      findings indicate that Nrg1 mediates the glucose repression of multiple genes
      through its direct binding to the specific promoter regions.

PMID- 24025682
TI  - Heme-binding properties of heme detoxification protein from Plasmodium
      falciparum.
AB  - The heme detoxification protein of the malaria parasite Plasmodium falciparum is
      involved in the formation of hemozoin, an insoluble crystalline form of heme.
      Although the disruption of hemozoin formation is the most widely used strategy
      for controlling the malaria parasite, the heme-binding properties of heme
      detoxification protein are poorly characterized. In this study, we established a
      method for the expression and purification of the non-tagged protein and
      characterized heme-binding properties. The spectroscopic features of non-tagged
      protein differ from those of the His-tagged protein, suggesting that the
      artificial tag interferes with the properties of the recombinant protein. The
      purified recombinant non-tagged heme detoxification protein had two heme-binding
      sites and exhibited a spectrum typical of heme proteins. A mechanism for hemozoin
      formation is proposed.

PMID- 24025683
TI  - Rhodamine-based "turn-on" fluorescent probe with high selectivity for Fe(2+)
      imaging in living cells.
AB  - A rhodamine-based "turn-on" fluorescent probe 1 was synthesized with high yield.
      The recognizing behavior displays high selectivity of 1 toward Fe(2+) with a 2:1
      complex, and 1 exhibits a stable response for Fe(2+) over a concentration range
      from 2 MUM to 24 MUM. Most importantly, probe is hardly interfered by other
      transition metal ions. Their fluorescent enhancement is observed in the presence
      of Fe(2+) because of the ring-open interactions of spirocyclic. All measurements
      are made in PBS buffer environments simulating biological conditions to make them
      suitable candidates for fluorescent labeling of biological systems. Confocal
      laser scanning microscopy experiments have proven that probe can be used to
      monitor Fe(2+) in living cells.

PMID- 24025684
TI  - Berberine exerts nephroprotective effect against cisplatin-induced kidney damage
      through inhibition of oxidative/nitrosative stress, inflammation, autophagy and
      apoptosis.
AB  - The aim of this study was to investigate the therapeutic activity of isoquinoline
      alkaloid berberine against cisplatin (CP)-induced nephrotoxicity in mice.
      Berberine was administered at daily doses of 1, 2 and 3 mg/kg by gavage for two
      successive days, 48 h after intraperitoneal CP injection (13 mg/kg). Mice were
      sacrificed 24 h after the last dose of berberine. Histopathological changes and
      the increase in serum creatinine and blood urea nitrogen (BUN) induced by CP were
      significantly ameliorated by berberine in a dose-dependent manner. Additionally,
      oxidative/nitrosative stress, evidenced by the increase in renal 4-hydroxynonenal
      (4-HNE), 3-nitrotyrosine (3-NT), cytochrome P450 E1 (CYP2E1) and heme oxygenase
      (HO-1) expression, was significantly reduced. The expression of nuclear factor
      kappaB (NF-kappaB), tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2
      (COX-2) and inducible nitric oxide synthase (iNOS) was markedly suppressed by
      berberine, indicating the inhibition of inflammatory response. Treatment of CP
      intoxicated animals with berberine also significantly reduced the expression of
      p53, active caspase-3 as well as autophagy marker light chain 3B (LC3B) in the
      kidneys. The results of the current study showed the nephroprotective activity of
      berberine against CP-induced renal injury, which could be attributed to the
      inhibition of oxidative/nitrosative stress, inflammation, autophagy and
      apoptosis.

PMID- 24025685
TI  - Biological importance of reactive oxygen species in relation to difficulties of
      treating pathologies involving oxidative stress by exogenous antioxidants.
AB  - Findings about involvement of reactive oxygen species (ROS) not only in defense
      processes, but also in a number of pathologies, stimulated discussion about their
      role in etiopathogenesis of various diseases. Yet questions regarding the role of
      ROS in tissue injury, whether ROS may serve as a common cause of different
      disorders or whether their uncontrolled production is just a manifestation of the
      processes involved, remain unexplained. Dogmatically, increased ROS formation is
      considered to be responsible for development of the so-called free-radical
      diseases. The present review discusses importance of ROS in various biological
      processes, including origin of life, evolution, genome plasticity, maintaining
      homeostasis and organism protection. This may be a reason why no significant
      benefit was found when exogenous antioxidants were used to treat free-radical
      diseases, even though their causality was primarily attributed to ROS. Here, we
      postulate that ROS unlikely play a causal role in tissue damage, but may readily
      be involved in signaling processes and as such in mediating tissue healing rather
      than injuring. This concept is thus in a contradiction to traditional
      understanding of ROS as deleterious agents. Nonetheless, under conditions of
      failing autoregulation, ROS may attack integral cellular components, cause cell
      death and deteriorate the evolving injury. 

PMID- 24025687
TI  - Psychotic experiences in a mental health clinic sample: implications for
      suicidality, multimorbidity and functioning.
AB  - BACKGROUND: Recent community-based research has suggested that psychotic
      experiences act as markers of severity of psychopathology. There has, however,
      been a lack of clinic-based research. We wished to investigate, in a clinical
      sample of adolescents referred to a state-funded mental health service, the
      prevalence of (attenuated or frank) psychotic experiences and the relationship
      with (i) affective, anxiety and behavioural disorders, (ii) multimorbid
      psychopathology, (iii) global functioning, and (iv) suicidal behaviour. METHOD:
      The investigation was a clinical case-clinical control study using semi
      structured research diagnostic psychiatric assessments in 108 patients newly
      referred to state adolescent mental health services. RESULTS: Psychotic
      experiences were prevalent in a wide range of (non-psychotic) disorders but were
      strong markers of risk in particular for multimorbid psychopathology (Z = 3.44, p
      = 0.001). Young people with psychopathology who reported psychotic experiences
      demonstrated significantly poorer socio-occupational functioning than young
      people with psychopathology who did not report psychotic experiences, which was
      not explained by multimorbidity. Psychotic experiences were strong markers of
      risk for suicidal behaviour. Stratified analyses showed that there was a greatly
      increased odds of suicide attempts in patients with a major depressive disorder
      [odds ratio (OR) 8.89, 95% confidence interval (CI) 1.59-49.83], anxiety disorder
      (OR 15.4, 95% CI 1.85-127.94) or behavioural disorder (OR 3.13, 95% CI 1.11-8.79)
      who also had psychotic experiences compared with patients who did not report
      psychotic experiences. CONCLUSIONS: Psychotic experiences (attenuated or frank)
      are an important but under-recognized marker of risk for severe psychopathology,
      including multimorbidity, poor functioning and suicidal behaviour in young people
      who present to mental health services.

PMID- 24025686
TI  - Pentamethylquercetin reduces fat deposition via Sirt1-mediated pathways in male
      obese mice induced by a high fat diet.
AB  - Pentamethylquercetin (PMQ) is a natural quercetin derivative found in a variety
      of edible herb. Although PMQ has potential as anti-diabetic agent, there have
      been no reports on its anti-adipogenic effects in the obese animals. This study
      investigated whether PMQ attenuates high-fat diet (HFD)-induced adipogenesis in
      the epididymal fat tissues of mice and explored its underlying mechanisms. In
      comparison with HFD-fed mice, mice fed with PMQ showed significantly lower body
      weight gain, adipose tissue mass, and plasma levels of triglyceride, total
      cholesterol, low-density lipoprotein cholesterol, and glucose, but higher plasma
      levels of high-density lipoprotein cholesterol. PMQ significantly reversed the
      HFD-induced regulation of Sirt1/mTOR signaling genes (Sirt1, mTOR, 4EBP1, and
      S6K1), and key adipogenic genes (PPARgamma, SREBP1, FAS, ATGL, HSL, and
      Perilipin) in the epididymal adipose tissues of obese mice. However, nicotinamide
      appeared to partly inhibit PMQ-mediated anti-adipogenic effects involved in this
      attenuation. These results suggested that PMQ inhibited visceral adipogenesis by
      suppressing the Sirt1-mediated mTOR and adipogenesis signaling cascades. It might
      be a potential candidate for the treatment of obesity. 

PMID- 24025688
TI  - Optimizing threshold-schedules for sequential approximate Bayesian computation:
      applications to molecular systems.
AB  - The likelihood-free sequential Approximate Bayesian Computation (ABC) algorithms
      are increasingly popular inference tools for complex biological models. Such
      algorithms proceed by constructing a succession of probability distributions over
      the parameter space conditional upon the simulated data lying in an epsilon-ball
      around the observed data, for decreasing values of the threshold epsilon. While
      in theory, the distributions (starting from a suitably defined prior) will
      converge towards the unknown posterior as epsilon tends to zero, the exact
      sequence of thresholds can impact upon the computational efficiency and success
      of a particular application. In particular, we show here that the current
      preferred method of choosing thresholds as a pre-determined quantile of the
      distances between simulated and observed data from the previous population, can
      lead to the inferred posterior distribution being very different to the true
      posterior. Threshold selection thus remains an important challenge. Here we
      propose that the threshold-acceptance rate curve may be used to determine
      threshold schedules that avoid local optima, while balancing the need to minimise
      the threshold with computational efficiency. Furthermore, we provide an algorithm
      based upon the unscented transform, that enables the threshold-acceptance rate
      curve to be efficiently predicted in the case of deterministic and stochastic
      state space models.

PMID- 24025689
TI  - Banding cytogenetic analysis in pediatric patients with acute lymphoblastic
      leukemia (ALL) in a Brazilian population.
AB  - BACKGROUND: Cytogenetic studies in Brazilian population about childhood acute
      lymphoblastic leukemia (ALL), the most common childhood malignancy, are scarce.
      Moreover, Brazilian race is very heterogeneous and is made by the confluence of
      people of several different origins, from the original Native Brazilians, with
      the influx of Portuguese colonizers, Black African slaves, and recent European,
      Arab and Japanese immigration. The purpose of this prospective, multicentric
      study was to assess the sociodemographic, clinic and cytogenetic characteristics
      of the children treated for ALL in the Northeast region of Brazil. RESULTS: This
      study includes thirty patients between 4 months and 17 years old treated for ALL
      from January 1st, 2009 to November 30th, 2010. Cytogenetic analysis showed that
      in nineteen out of thirty patients (64%) presented some chromosome abnormalities,
      in which 53% corresponds to numerical abnormalities, 21% structural and numerical
      abnormalities, and 26% only structural changes. Moreover, seven patients
      presented complexes karyotype not yet described in the literature. Taken together
      these results show the importance of the cytogenetic analysis in ALL pediatric
      patients and illustrates that the studied population presented unexpected
      complexes karyotypes which were correlated to poor outcome. CONCLUSION: The
      results demonstrate the importance of banding cytogenetics for ALL diagnosis
      despite the use of most modern techniques such as FISH and aCGH, and provide
      reliable insight into the ALL in Brazil.

PMID- 24025690
TI  - Microscopic theory of non-adiabatic response in real and imaginary time.
AB  - We present a general approach to describe slowly driven quantum systems both in
      real and imaginary time. We highlight many similarities, qualitative and
      quantitative, between real and imaginary time evolution. We discuss how the
      metric tensor and the Berry curvature can be extracted from both real and
      imaginary time simulations as a response of physical observables. For quenches
      ending at or near the quantum critical point, we show the utility of the scaling
      theory for detecting the location of the quantum critical point by comparing
      sweeps at different velocities. We briefly discuss the universal relaxation to
      equilibrium of systems after a quench. We finally review recent developments of
      quantum Monte Carlo methods for studying imaginary time evolution. We illustrate
      our findings with explicit calculations using the transverse-field Ising model in
      one dimension. 

PMID- 24025691
TI  - Azacitidine induces profound genome-wide hypomethylation in primary
      myelodysplastic bone marrow cultures but may also reduce histone acetylation.

PMID- 24025692
TI  - Pterygodermatites (Mesopectines) quentini (Nematoda, Rictulariidae), a parasite
      of Praomys rostratus (Rodentia, Muridae) in Mali: scanning electron and light
      microscopy.
AB  - Pterygodermatites (Mesopectines) quentini n. sp. (Nematoda, Rictulariidae) is
      described from the murine host Praomys rostratus in the south of the Republic of
      Mali. It differs from other species of the subgenus by the morphology of the
      head, which bears four simple cephalic papillae and a nearly axial oral opening,
      the number of caudal papillae, the number of precloacal cuticular formations,
      unequal spicules and the ratio of spicule lengths/body length. The use of
      scanning electron microscopy in combination with conventional light microscopy
      enabled us to give a detailed description of the morphological characters of this
      new species. 

PMID- 24025693
TI  - Doubling of serum creatinine as an outcome after renal transplant - pathological
      evidence of graft biopsy.
AB  - Background Doubling of serum creatinine (DSC) in transplantation has been seen as
      the end-point of renal function without pathological evidence. We conducted this
      study to elucidate the relationship between DSC and pathological findings.
      Material and Methods We conducted a retrospective cohort study to illustrate
      pathologic changes in patients receiving a kidney biopsy in the previous 5 years
      with clinicopathological correlations to DSC and proteinuria. Results Of a total
      of 99 kidney recipients (146 biopsies), results of graft biopsy were as follows:
      calcineurin inhibitor toxicity (CNI) (38.7%) and rejection (36.9%). Compared to
      males, females had higher proportions of class I (p=0.003) and class II PRA
      (p<0.001), and a higher rejection rate (p=0.042), but had the same clinical
      outcomes as males, like eGFR at follow-up (p=0.882), DSC (p=0.703), and
      proteinuria (p=0.745). Pathological diagnoses and findings were related to
      proteinuria: glomerulopathy (HR=4.9, p=0.01), AMR (HR=2.5, p=0.025), especially
      acute AMR (HR=2.9, p=0.008), chronic glomerular change (HR=10.2, p=0.002),
      arteriolar hyaline (HR=2.3, p=0.026), and mesangial matrix change (HR=6.3,
      p=0.002). BK nephropathy and rejection were the only 2 risk factors. Pathological
      findings favoring AMR (PTC infiltration and glomerulitis) showed a greater risk
      of DSC compared with those favoring CMR (interstitial inflammation, intimal
      arteritis, and tubulitis). DSC was correlated with clinical manifestation
      (rejection) and provided strong pathological evidence. Conclusions There was more
      acute rejection and chronic pathological change in women, but outcomes were the
      same due to less activity of renin-angiotensin-aldosterone and hyperfiltration in
      females. DSC as an end-point of graft function can be used to identify
      recipients, especially AMR or mixed AMR and CMR. 1. All forms of support received
      by each author: None of the authors received support. 2. Any potential conflict
      of interest for each author: No conflict of interest for any of the authors. 

PMID- 24025695
TI  - Schizophrenia in DSM-5: assets and liabilities.

PMID- 24025694
TI  - Replication in a Japanese population that a MIR30E gene variation is associated
      with schizophrenia.

PMID- 24025696
TI  - Duration of untreated psychosis in adolescents: ethnic differences and clinical
      profiles.
AB  - BACKGROUND: Duration of Untreated Psychosis (DUP) is an important measure
      associated with outcome of psychosis. This first study in the UK compared DUP
      between adolescent and adult-onset individuals and explored whether the
      adolescent-onset group showed variations in DUP that could be accounted for by
      sociodemographic and selected risk factors. METHODS: This naturalistic cohort
      study included 940 new first-episode psychosis cases aged 14-35years (136
      adolescent-onset versus 804 adult-onset psychotic individuals) referred to nine
      Early Intervention Services for Psychosis in London (2003-2009). Sociodemographic
      characteristics, age of onset, family history of mental illness, duration of
      untreated psychosis, suicidality and substance use information were collected at
      entry to the services. RESULTS: Adolescents presented with significantly greater
      median DUP (179days) than adults (81days, p=0.005). Large differences in DUP were
      found amongst adolescent ethnic groups (median DUP: White: 454days; Black:
      103days; Asian and mixed: 28.5days). In addition, younger age of onset and higher
      lifetime cannabis use were associated with longer treatment delay amongst
      adolescents. CONCLUSIONS: This study of DUP in adolescent-onset psychosis found
      it to be approximately twice the length of DUP amongst adults. For the adolescent
      White sub-group, DUP was far greater than the UK Department of Health target
      (<3months). Both the high rates of lifetime cannabis use and the lower age of
      onset might explain the long DUP in this ethnic group. Physicians need to be
      particularly vigilant about identifying and managing early psychosis in
      adolescents.

PMID- 24025697
TI  - Clozapine-induced cardiomyopathy: a first case in Japan.

PMID- 24025699
TI  - A survey of manual vacuum aspiration's experiences among the new medical
      graduates in Thailand.
AB  - BACKGROUND: Despite Thai laws permitting abortion conducted by registered medical
      practitioners, unsafe abortion still kills and maims Thai women as a result of
      inadequate access to safe abortion services. Surgical evacuation of the uterus by
      manual vacuum aspirator (MVA) is a safe and effective technique recommended by
      the World Health Organization (WHO) guidelines. This study assessed new medical
      graduates' MVA experiences during their clinical years in medical schools.
      METHODS: Cross-sectional questionnaire surveys on all new medical graduates
      participating in the annual assembly arranged by the Ministry of Public Health in
      2010 and 2012 were applied. Descriptive and inferential statistics were employed
      for data analysis. RESULTS: The significant minority of new graduates (44% and
      43% in 2010 and 2012 batches) had seen but never used MVA. The proportion of
      graduates who had 'never seen' reduced from 32% in 2010 to 23% in 2012 while the
      proportion of 'ever used' had noticeably increased from 24% to 34% in
      corresponding years. Graduates from medical schools outside Bangkok and vicinity
      and those reporting confidence in their surgical skills tended to have more MVA
      experience. The 2012 graduation year was also positively related to higher
      experience on MVA. CONCLUSION: Though the proportion of graduates who had ever
      used MVA was still low in 2012, a positive change from that in 2010 was observed.
      Medical schools outside Bangkok and vicinity provided more opportunities for
      learning MVA. It is recommended that medical schools, especially in Bangkok and
      vicinity should provide more MVA learning opportunities for students. Adequate
      training and regular hands-on MVA practice should be incorporated into a wide
      range of clinical practice.

PMID- 24025700
TI  - Cumulative dermatologic toxicity with ipilimumab and vemurafenib responsive to
      corticosteroids.
AB  - Dermatologic toxicity is a known reaction of ipilimumab and vemurafenib. Because
      of the lack of effective treatments and aggressive nature of melanoma, treatments
      are often discontinued and new treatments are initiated in rapid succession. We
      report what we believe to be the first case of cumulative dermatologic toxicity
      secondary to rapid-sequential treatment with ipilimumab and vemurafenib for
      metastatic melanoma that responded to high-dose steroids. This case highlights
      the combined toxicity of these two drugs that can occur as a result of
      overlapping toxicity. It also illustrates the need for a substantial wash out
      period between rapid cycling of these two drugs secondary to ipilimumab's long
      half-life. 

PMID- 24025698
TI  - Three steps to the immortality of cancer cells: senescence, polyploidy and self
      renewal.
AB  - Metastatic cancer is rarely cured by current DNA damaging treatments, apparently
      due to the development of resistance. However, recent data indicates that tumour
      cells can elicit the opposing processes of senescence and stemness in response to
      these treatments, the biological significance and molecular regulation of which
      is currently poorly understood. Although cellular senescence is typically
      considered a terminal cell fate, it was recently shown to be reversible in a
      small population of polyploid cancer cells induced after DNA damage. Overcoming
      genotoxic insults is associated with reversible polyploidy, which itself is
      associated with the induction of a stemness phenotype, thereby providing a
      framework linking these separate phenomena. In keeping with this suggestion,
      senescence and autophagy are clearly intimately involved in the emergence of self
      renewal potential in the surviving cells that result from de-polyploidisation.
      Moreover, subsequent analysis indicates that senescence may paradoxically be
      actually required to rejuvenate cancer cells after genotoxic treatments. We
      propose that genotoxic resistance is thereby afforded through a programmed life
      cycle-like process which intimately unites senescence, polyploidy and stemness. 

PMID- 24025701
TI  - Comparative evaluation of rumen metagenome community using qPCR and MG-RAST.
AB  - Microbial profiling of metagenome communities have been studied extensively using
      MG-RAST and other related metagenome annotation databases. Although, database
      based taxonomic profiling provides snapshots of the metagenome architecture,
      their reliability needs to be validated through more accurate methods. Here, we
      performed qPCR based absolute quantitation of selected rumen microbes in the
      liquid and solid fraction of the rumen fluid of river buffalo adapted to varying
      proportion of concentrate to green or dry roughages and compared with the MG-RAST
      based annotation of the metagenomes sequences of 16S r-DNA amplicons and high
      throughput shotgun sequencing. Animals were adapted to roughage-to-concentrate
      ratio in the proportion of 50:50, 75:25 and 100:00, respectively for six weeks.
      At the end of each treatment, rumen fluid was collected at 3 h post feeding. qPCR
      revealed that the relative abundance of Prevotella bryantii was higher, followed
      by the two cellulolytic bacteria Fibrobacter succinogens and Ruminococcus
      flavefaciens that accounted up to 1.33% and 0.78% of the total rumen bacteria,
      respectively. While, Selenomonas ruminantium and archaea Methanomicrobiales were
      lower in microbial population in the rumen of buffalo. There was no statistically
      significant difference between the enumerations shown by qPCR and analysis of the
      shotgun sequencing data by MG-RAST except for Prevotella. These results indicate
      the variations in abundance of different microbial species in buffalo rumen under
      varied feeding regimes as well as in different fractions of rumen liquor, i.e.
      solid and the liquid. The results also present the reliability of shotgun
      sequencing to describe metagenome and analysis/annotation by MG-RAST. 

PMID- 24025702
TI  - Dolichocarotids: echo-color Doppler evaluation and clinical role.
AB  - AIMS: Dolichocarotids(DCs) represent a rare(2-6%) carotid imaging finding in the
      general population that may be free of clinical significance or be associated
      with cerebrovascular events. Their detection is traditionally assigned to carotid
      echo-color Doppler(ECD) and selective angiography(the standard method). The
      primary aim of this study was to estimate the sensitivity, specificity and
      accuracy of ECD in detecting DCs. Moreover, we monitored the DC curvature angle
      and the incidence of TIA, ischemic stroke, myocardial infarction and
      cardiovascular death over a five-year followup period. METHODS: A total of 112
      consecutive patients with DCs(80 men, mean age: 61+/-7 years) were recruited for
      carotid ECD and carotid angiography due to the persistence of neurological
      symptoms not well explained on ultrasound evaluations, according to the current
      guidelines. RESULTS: ECD proved to have 100% sensitivity in detecting tortuosity
      and coiling and 96% sensitivity in detecting kinking, with an overall accuracy
      ranging from 92% to 100%. The specificity was 75% for tortuosity, 91% for kinking
      and 100% for coiling. During the five-year follow-up period, there was a
      statistically significant increase in tortuosity(61+/-11 degrees  at baseline
      versus 81+/-11 degrees  after five years, p<0.001) and the kinking curvature
      angle(97+/-3 degrees  at baseline versus 100+/-3 degrees  at five years,
      p<0.001), whilst no differences were observed with respect to coiling(136+/-10
      degrees  at baseline versus 138+/-11 degrees  at five years, p=ns). Moreover,
      kinking was found to be more frequently statistically associated with
      cardiovascular death than tortuosity(p=0.005). CONCLUSIONS: DCs predispose
      patients to potentially disabling and fatal events. ECD plays a primary role in
      the detection of DCs and therefore should be considered to be a secure and
      reproducible technique.

PMID- 24025703
TI  - Prediction of the presence of insulin resistance using general health checkup
      data in Japanese employees with metabolic risk factors.
AB  - AIM: The aim of the current study was to develop a predictive model of insulin
      resistance using general health checkup data in Japanese employees with one or
      more metabolic risk factors. METHODS: We used a database of 846 Japanese
      employees with one or more metabolic risk factors who underwent general health
      checkup and a 75-g oral glucose tolerance test (OGTT). Logistic regression models
      were developed to predict existing insulin resistance evaluated using the Matsuda
      index. The predictive performance of these models was assessed using the C
      statistic. RESULTS: The C statistics of body mass index (BMI), waist
      circumference and their combined use were 0.743, 0.732 and 0.749, with no
      significant differences. The multivariate backward selection model, in which BMI,
      the levels of plasma glucose, high-density lipoprotein (HDL) cholesterol, log
      transformed triglycerides and log-transformed alanine aminotransferase and
      hypertension under treatment remained, had a C statistic of 0.816, with a
      significant difference compared to the combined use of BMI and waist
      circumference (p<0.01). The C statistic was not significantly reduced when the
      levels of log-transformed triglycerides and log-transformed alanine
      aminotransferase and hypertension under treatment were simultaneously excluded
      from the multivariate model (p=0.14). On the other hand, further exclusion of any
      of the remaining three variables significantly reduced the C statistic (all
      p<0.01). CONCLUSIONS: When predicting the presence of insulin resistance using
      general health checkup data in Japanese employees with metabolic risk factors, it
      is important to take into consideration the BMI and fasting plasma glucose and
      HDL cholesterol levels.

PMID- 24025705
TI  - Mapping the intramolecular signal propagation pathways in protein using Bayesian
      change point analysis of atomic motions.
AB  - We propose to use change points of atomic positions in the molecular dynamics
      trajectory as indicators of the propagating signals in protein. We designate
      these changes as signals because they can propagate within the molecule in the
      form of "perturbation wave", transmit energy or information between different
      parts of protein, and serve as allosteric signals. We found that change points
      can distinguish between thermal fluctuations of atoms (noise) and signals in a
      protein despite the differences in the motility of amino acid residues.
      Clustering of the spatially close residues that were experiencing change points
      close in time, allowed us to map pathways of signal propagation in a protein at
      the atomic level of resolution. We propose a potential mechanism for the origin
      of the signal and its propagation that relies on the autonomic coherence
      resonance in atomic fluctuations. According to this mechanism, random
      synchronization of fluctuations of neighboring atoms results in a resonance,
      which increases amplitude of vibration of these atoms. This increase can be
      transmitted to the atoms colliding with the resonant atoms, leading to the
      propagating signal. The wavelet-based coherence analysis of the inter-atomic
      distances between carbon-alpha atoms and surrounding atoms for the residue pairs
      that belong to the same communication pathway allowed us to find time periods
      with temporarily locked phases, confirming the occurrence of conditions for
      resonance. Analysis of the mapped pathways demonstrated that they form a network
      that connects different regions of the protein. 

PMID- 24025704
TI  - Influence of eye size and beam entry angle on dose to non-targeted tissues of the
      eye during stereotactic x-ray radiosurgery of AMD.
AB  - Age-related macular degeneration is a leading cause of vision loss for the
      elderly population of industrialized nations. The IRay(r) Radiotherapy System,
      developed by Oraya(r) Therapeutics, Inc., is a stereotactic low-voltage
      irradiation system designed to treat the wet form of the disease. The IRay System
      uses three robotically positioned 100 kVp collimated photon beams to deliver an
      absorbed dose of up to 24 Gy to the macula. The present study uses the Monte
      Carlo radiation transport code MCNPX to assess absorbed dose to six non-targeted
      tissues within the eye-total lens, radiosensitive tissues of the lens, optic
      nerve, distal tip of the central retinal artery, non-targeted portion of the
      retina, and the ciliary body--all as a function of eye size and beam entry angle.
      The ocular axial length was ranged from 20 to 28 mm in 2 mm increments, with the
      polar entry angle of the delivery system varied from 18 degrees  to 34 degrees 
      in 2 degrees  increments. The resulting data showed insignificant variations in
      dose for all eye sizes. Slight variations in the dose to the optic nerve and the
      distal tip of the central retinal artery were noted as the polar beam angle
      changed. An increase in non-targeted retinal dose was noted as the entry angle
      increased, while the dose to the lens, sensitive volume of the lens, and ciliary
      body decreased as the treatment polar angle increased. Polar angles of 26 degrees
      or greater resulted in no portion of the sensitive volume of the lens receiving
      an absorbed dose of 0.5 Gy or greater. All doses to non-targeted structures
      reported in this study were less than accepted thresholds for post-procedure
      complications. 

PMID- 24025706
TI  - Inflammatory mediators accelerate metabolism of benzo[a]pyrene in rat alveolar
      type II cells: the role of enhanced cytochrome P450 1B1 expression.
AB  - Long-term deregulated inflammation represents one of the key factors contributing
      to lung cancer etiology. Previously, we have observed that tumor necrosis factor
      alpha (TNF-alpha), a major pro-inflammatory cytokine, enhances genotoxicity of
      benzo[a]pyrene (B[a]P), a highly carcinogenic polycyclic aromatic hydrocarbon, in
      rat lung epithelial RLE-6TN cells, a model of alveolar type II cells. Therefore,
      we analyzed B[a]P metabolism in RLE-6TN cells under inflammatory conditions,
      simulated using either recombinant TNF-alpha, or a mixture of inflammatory
      mediators derived from activated alveolar macrophage cell line. Inflammatory
      conditions significantly accelerated BaP metabolism, as evidenced by decreased
      levels of both parent B[a]P and its metabolites. TNF-alpha altered production of
      the metabolites associated with dihydrodiol-epoxide and radical cation pathways
      of B[a]P metabolism, especially B[a]P-dihydrodiols, and B[a]P-diones. We then
      evaluated the role of cytochrome P450 1B1 (CYP1B1), which is strongly up
      regulated in cells treated with B[a]P under inflammatory conditions, in the
      observed effects. The siRNA-mediated CYP1B1 knock-down increased levels of B[a]P
      and reduced formation of stable DNA adducts, thus confirming the essential role
      of CYP1B1 in B[a]P metabolism under inflammatory conditions. TNF-alpha also
      reduced expression of aldo-keto reductase 1C14, which may compete with CYP1B1 for
      B[a]P-7,8-dihydrodiol and divert it from the formation of ultimate B[a]P
      dihydrodiol epoxide. Together, the present data suggests that the CYP1B1
      catalyzed metabolism of polycyclic aromatic hydrocarbons might contribute to
      their enhanced bioactivation and genotoxic effects under inflammatory conditions.

PMID- 24025709
TI  - Increasing prevalence and incidence rates of multiple sclerosis in Kuwait.
AB  - BACKGROUND: Kuwait was considered as low to intermediate risk area for MS.
      OBJECTIVES: To determine the prevalence and incidence rates of MS among Kuwaiti
      nationals based on 2011 population census. METHODS: This cross-sectional study
      was conducted between October 2010 and April 2013 using the newly developed
      national MS registry in Kuwait. Patients with a diagnosis of MS according to 2010
      revised McDonald criteria were identified. The crude, age- and sex-specific
      prevalence and incidence rates among Kuwaiti patients were calculated. RESULTS:
      1176 MS patients were identified of which 927 (78.8%) were Kuwaitis and 249
      (21.2%) were expatriates. Among Kuwaiti patients, female to male ratio was 1.8:1
      with a mean age of 35.40 +/- 10.99 years. The prevalence rate of MS was 85.05 per
      100,000 persons (95% CI: 82.80 - 87.04). There was a peak in prevalence among
      patients aged 30-39 years. The incidence of MS was 6.88 per 100,000 persons (95%
      CI 5.52-8.55). Between 2003 and 2011, the incidence increased 3.22 and 2.54 times
      in women and men respectively. CONCLUSION: Kuwait is considered a high-risk area
      for MS. The significant increase in prevalence and incidence rates may represent
      a true increase despite the improvement in case ascertainment and case
      definition.

PMID- 24025707
TI  - Importance of sulfate groups for the macrophage-stimulating activities of
      ascophyllan isolated from the brown alga Ascophyllum nodosum.
AB  - To investigate the role of sulfate groups on the macrophage-stimulating
      activities of ascophyllan, we prepared desulfated ascophyllan, and its effects on
      RAW264.7 cells were compared with native ascophyllan. The chemical structural
      analysis revealed that nearly 21% of sulfate groups of ascophyllan were removed
      by desulfation reaction, while no significant changes in the molecular mass and
      monosaccharide composition occurred after desulfation. NO- and cytokine- (TNF
      alpha and G-CSF) inducing activities of the desulfated ascophyllan on RAW264.7
      cells were significantly decreased as compared to native ascophyllan.
      Furthermore, the activity of desulfated ascophyllan to induce reactive oxygen
      species (ROS) generation from RAW264.7 cells decreased to almost negligible
      level. Our results suggest that the level of sulfate groups of ascophyllan is an
      important structural element responsible for the macrophage-stimulating
      activities. Probably, even the limited removal of sulfate residues sensitive to
      desulfation reaction may result in significant decrease in the bioactivities of
      ascophyllan. 

PMID- 24025710
TI  - Iron-mediated effect of alcohol on hepatocyte differentiation in HepaRG cells.
AB  - The development of alcoholic liver diseases depends on the ability of hepatocyte
      to proliferate and differentiate in the case of alcohol-induced injury. Our
      previous work showed an inhibitory effect of alcohol on hepatocyte proliferation.
      However, the effect of alcohol on hepatocyte differentiation has not yet been
      precisely characterized. In the present study, we evaluated the effect of alcohol
      on hepatocyte differentiation in relationship with changes of iron metabolism in
      HepaRG cells. This unique bipotent human cell line can differentiate into
      hepatocytes and biliary epithelial cells, paralleling liver development. Results
      showed that alcohol reduced cell viability, total protein level and enhanced
      hepatic enzymes leakage in differentiated HepaRG cells. Moreover, it caused cell
      enlargement, decreased number of hepatocyte and expression of C/EBPalpha as well
      as bile canaliculi F-actin. Alcohol increased expression of hepatic cell-specific
      markers and alcohol-metabolizing enzymes (ADH2, CYP2E1). This was associated with
      a lipid peroxidation and an iron excess expressed by an increase in total iron
      content, ferritin level, iron uptake as well as an overexpression of genes
      involved in iron transport and storage. Alcohol-induced hepatoxicity was
      amplified by exogenous iron via exceeding iron overload. Taken together, our data
      demonstrate that in differentiated hepatocytes, alcohol reduces proliferation
      while increasing expression of hepatic cell-specific markers. Moreover, iron
      overload could be one of the underlying mechanisms of effect of alcohol on the
      whole differentiation process of hepatocytes. 

PMID- 24025711
TI  - Carbon disulfide exposure at peri-implantation disrupts embryo implantation by
      decreasing integrin beta3 expression in the uterine tissue of pregnant mice.
AB  - Carbon disulfide (CS2) exposure might disrupt embryo implantation in females
      during pregnancy but the relevant mechanism remains unclear. Since integrin beta3
      has shown to be one of the cell adhesion molecules involved in embryo
      implantation, the current study examined the effect of CS2 exposure during the
      peri-implantation period on the protein and mRNA expression of integrin beta3 and
      its DNA methylation degree in the uterine tissue of gestational mice. Exposure
      was on the 3rd day of gestation (GD3), GD4, GD5 and GD6, respectively, one time
      administration (631.4 mg/kg). The number of implanted embryos on GD9 was observed
      and compared with the control, it was decreased by 32.92%, 56.11%, 56.11% and
      51.21%, respectively, which revealed that GD4 and GD5 were the most sensitive
      time for embryotoxicity. The protein and mRNA expression of integrin beta3 were
      detected each day after exposure till the GD7 endpoint. It down-regulated the
      protein and mRNA expression of integrin beta3 in uterine tissue and there was a
      positive correlation between the number of embryos and the expression of protein
      on the first and second day after exposure. However, the degree of integrin beta3
      DNA methylation was not affected, which was detected by bisulfite sequencing
      polymerase chain reaction (BSP) method. These findings suggest that the decreased
      protein and mRNA level of integrin beta3 in the uterine tissue after mice
      exposure to CS2 might be relevant to the underlying mechanism of embryo
      implantation disorders, but DNA methylation of integrin beta3 does not contribute
      to this action.

PMID- 24025712
TI  - Proteome profiling of cancer-associated fibroblasts identifies novel
      proinflammatory signatures and prognostic markers for colorectal cancer.
AB  - PURPOSE: Cancer-associated fibroblasts (CAF) are essential components of the
      stroma that play a critical role in cancer progression. This study aimed to
      identify novel CAFs markers that might contribute to the invasion and the
      prognosis of colorectal cancer. EXPERIMENTAL DESIGN: The azoxymethane/dextran
      sodium sulfate mouse model of sporadic colon cancer represents an adequate source
      for the isolation of CAFs and normal fibroblasts. By using the explants
      technique, we purified CAFs and normal fibroblasts from colon tissues. Whole-cell
      extracts and supernatants were subjected to in-depth quantitative proteomic
      analysis by tandem mass spectrometry. Further validations of upregulated proteins
      in CAFs were carried out by chemokine microarray and immunohistochemical analyses
      of mouse and human tissues. RESULTS: Using a fold-change of 1.4 or more, we found
      132 and 125 differentially expressed proteins in whole-cell extracts and
      supernatants, respectively. We found CAFs-associated proinflammatory and
      desmoplastic signatures. The proinflammatory signature was composed of several
      cytokines. Among them, CCL2 and CCL8 caused an increase in migration and invasion
      of colorectal cancer KM12 cells. The desmoplastic signature was composed of 30
      secreted proteins. In mouse and human samples, expression of LTBP2, CDH11,
      OLFML3, and, particularly, FSTL1 was significantly increased in the tumoral
      stroma, without significant expression in the cancer epithelial cells. The
      combination of CALU and CDH11 stromal expression showed a significant association
      with disease-free survival and poor prognosis. CONCLUSION: We have identified
      LTBP2, CDH11, OLFML3, and FSTL1 as selective biomarkers of cancer stroma, and
      CALU and CDH11 as candidate stromal biomarkers of prognostic significance in
      colon cancer.

PMID- 24025713
TI  - Targeting of NAD metabolism in pancreatic cancer cells: potential novel therapy
      for pancreatic tumors.
AB  - PURPOSE: Here, we describe a novel interplay between NAD synthesis and
      degradation involved in pancreatic tumor growth. EXPERIMENTAL DESIGN: We used
      human pancreatic cancer cells, both in vitro (cell culture experiments) and in
      vivo (xenograft experiments), to demonstrate the role of NAD synthesis and
      degradation in tumor cell metabolism and growth. RESULTS: We demonstrated that
      pharmacologic and genetic targeting of Nampt, the key enzyme in the NAD salvage
      synthesis pathway, inhibits cell growth and survival of pancreatic cancer cells.
      These changes were accompanied by a reduction of NAD levels, glycolytic flux,
      lactate production, mitochondrial function, and levels of ATP. The massive
      reduction in overall metabolic activity induced by Nampt inhibition was
      accompanied by a dramatic decrease in pancreatic tumor growth. The results of the
      mechanistic experiments showed that neither the NAD-dependent enzymes PARP-1 nor
      SIRT1 play a significant role on the effect of Nampt inhibition on pancreatic
      cancer cells. However, we identified a role for the NAD degradation pathway
      mediated by the NADase CD38 on the sensitivity to Nampt inhibition. The
      responsiveness to Nampt inhibition is modulated by the expression of CD38; low
      levels of this enzyme decrease the sensitivity to Nampt inhibition. In contrast,
      its overexpression decreased cell growth in vitro and in vivo, and further
      increased the sensitivity to Nampt inhibition. CONCLUSIONS: Our study
      demonstrates that NAD metabolism is essential for pancreatic cancer cell survival
      and proliferation and that targeting NAD synthesis via the Nampt pathway could
      lead to novel therapeutic treatments for pancreatic cancer.

PMID- 24025715
TI  - Sterol-induced dislocation of 3-hydroxy-3-methylglutaryl coenzyme A reductase
      from membranes of permeabilized cells.
AB  - The polytopic endoplasmic reticulum (ER)-localized enzyme 3-hydroxy-3
      methylglutaryl CoA reductase catalyzes a rate-limiting step in the synthesis of
      cholesterol and nonsterol isoprenoids. Excess sterols cause the reductase to bind
      to ER membrane proteins called Insig-1 and Insig-2, which are carriers for the
      ubiquitin ligases gp78 and Trc8. The resulting gp78/Trc8-mediated ubiquitination
      of reductase marks it for recognition by VCP/p97, an ATPase that mediates
      subsequent dislocation of reductase from ER membranes into the cytosol for
      proteasomal degradation. Here we report that in vitro additions of the oxysterol
      25-hydroxycholesterol (25-HC), exogenous cytosol, and ATP trigger dislocation of
      ubiquitinated and full-length forms of reductase from membranes of permeabilized
      cells. In addition, the sterol-regulated reaction requires the action of Insigs,
      is stimulated by reagents that replace 25-HC in accelerating reductase
      degradation in intact cells, and is augmented by the nonsterol isoprenoid
      geranylgeraniol. Finally, pharmacologic inhibition of deubiquitinating enzymes
      markedly enhances sterol-dependent ubiquitination of reductase in membranes of
      permeabilized cells, leading to enhanced dislocation of the enzyme. Considered
      together, these results establish permeabilized cells as a viable system in which
      to elucidate mechanisms for postubiquitination steps in sterol-accelerated
      degradation of reductase. 

PMID- 24025714
TI  - Nudel/NudE and Lis1 promote dynein and dynactin interaction in the context of
      spindle morphogenesis.
AB  - Lis1, Nudel/NudE, and dynactin are regulators of cytoplasmic dynein, a minus end
      directed, microtubule (MT)-based motor required for proper spindle assembly and
      orientation. In vitro studies have shown that dynactin promotes processive
      movement of dynein on MTs, whereas Lis1 causes dynein to enter a persistent force
      generating state (referred to here as dynein stall). Yet how the activities of
      Lis1, Nudel/NudE, and dynactin are coordinated to regulate dynein remains poorly
      understood in vivo. Working in Xenopus egg extracts, we show that Nudel/NudE
      facilitates the binding of Lis1 to dynein, which enhances the recruitment of
      dynactin to dynein. We further report a novel Lis1-dependent dynein-dynactin
      interaction that is essential for the organization of mitotic spindle poles.
      Finally, using assays for MT gliding and spindle assembly, we demonstrate an
      antagonistic relationship between Lis1 and dynactin that allows dynactin to
      relieve Lis1-induced dynein stall on MTs. Our findings suggest the interesting
      possibility that Lis1 and dynactin could alternately engage with dynein to allow
      the motor to promote spindle assembly. 

PMID- 24025717
TI  - The oncogenic TBX3 is a downstream target and mediator of the TGF-beta1 signaling
      pathway.
AB  - The T-box transcription factor, TBX3, plays an important role in embryonic
      development, and haploinsufficiency of TBX3 causes ulnar-mammary syndrome.
      Overexpression of TBX3, on the other hand, is associated with several cancers,
      and preliminary evidence suggests that increased levels of TBX3 may inhibit cell
      proliferation but promote tumor migration and invasion. Although this suggests
      that deregulated levels of TBX3 are deleterious in development and promotes
      disease, very little is known about the signaling pathways that regulate TBX3
      expression. Here we show that overexpressing TBX3 inhibits proliferative ability
      while promoting the migration of breast epithelial cells. We demonstrate that the
      transforming growth factor beta1 (TGF-beta1) pathway up-regulates TBX3 protein
      and mRNA levels and show a detailed transcriptional mechanism by which this
      occurs. Using in vitro and in vivo assays, we show that Smad3/4 and JunB bind and
      cooperatively regulate TBX3 promoter activity through a Smad-binding element at 
      67 base pairs. Further, we show that TBX3 plays a pivotal role in mediating the
      antiproliferative and promigratory role of TGF-beta1 in breast epithelial and
      skin keratinocytes. This study identifies the TGF-beta1 signaling pathway as a
      potentially important player in the regulation of TBX3 in development and cancer.

PMID- 24025718
TI  - Perspectives on clinical magnetic particle imaging.
AB  - After realizing the worlds' first preclinical magnetic particle imaging (MPI)
      demonstrator, Philips is now realizing the worlds' first whole-body clinical
      prototype to prove the feasibility of MPI for clinical imaging. After a brief
      introduction of the basic MPI imaging process, this contribution presents an
      overview on the determining factors for key properties, i.e., spatial resolution,
      acquisition speed, sensitivity, and quantitativeness, and how these properties
      are influenced by scaling up from preclinical to clinical instrumentation.
      Furthermore, it is discussed how this scale up affects the physiological
      compatibility of the method as well as hardware parameters such as power
      requirements for drive field generation, selection and focus field generation,
      and the design of the receive chain of the MPI device.

PMID- 24025719
TI  - Lingual thyroid.

PMID- 24025716
TI  - Adenovirus RIDalpha uncovers a novel pathway requiring ORP1L for lipid droplet
      formation independent of NPC1.
AB  - Niemann-Pick disease type C (NPC) is caused by mutations in NPC1 or NPC2, which
      coordinate egress of low-density-lipoprotein (LDL)-cholesterol from late
      endosomes. We previously reported that the adenovirus-encoded protein RIDalpha
      rescues the cholesterol storage phenotype in NPC1-mutant fibroblasts. We show
      here that RIDalpha reconstitutes deficient endosome-to-endoplasmic reticulum (ER)
      transport, allowing excess LDL-cholesterol to be esterified by acyl
      CoA:cholesterol acyltransferase and stored in lipid droplets (LDs) in NPC1
      deficient cells. Furthermore, the RIDalpha pathway is regulated by the oxysterol
      binding protein ORP1L. Studies have classified ORP1L as a sterol sensor involved
      in LE positioning downstream of GTP-Rab7. Our data, however, suggest that ORP1L
      may play a role in transport of LDL-cholesterol to a specific ER pool designated
      for LD formation. In contrast to NPC1, which is dispensable, the RIDalpha/ORP1L
      dependent route requires functional NPC2. Although NPC1/NPC2 constitutes the
      major pathway, therapies that amplify minor egress routes for LDL-cholesterol
      could significantly improve clinical management of patients with loss-of-function
      NPC1 mutations. The molecular identity of putative alternative pathways, however,
      is poorly characterized. We propose RIDalpha as a model system for understanding
      physiological egress routes that use ORP1L to activate ER feedback responses
      involved in LD formation. 

PMID- 24025720
TI  - Vitamin D and the heart: what is the truth?

PMID- 24025721
TI  - Multiple cutaneous hemangiomas in a patient with combined pituitary hormone
      deficiency.
AB  - Combined pituitary hormone deficiency (CPHD) refers to a rare heterogeneous group
      of conditions in which there is a deficiency in at least two anterior pituitary
      hormones. Patients with POU1F1 mutations show a combined pituitary deficiency
      with low or absent levels of growth hormone, prolactin, and thyroid-stimulating
      hormone. In this study, a 7-month-old girl with a CPHD is presented. She had
      facial dysmorphologic features, hypertrichosis, and hypotonia. Additionally, she
      also presented with multiple cutaneous hemangioma that until now has not been
      reported in association with this disorder.

PMID- 24025722
TI  - Pediatric idiopathic intracranial hypertension and the underlying endocrine
      metabolic dysfunction: a pilot study.
AB  - AIM: To unravel the potential idiopathic intracranial hypertension (IIH)
      endocrine-metabolic comorbidities by studying the natural (and targeted drug
      modified) history of disease in children. IIH is a disorder of unclear
      pathophysiology, characterized by raised intracranial pressure without
      hydrocephalus or space-occupying lesion coupled with normal cerebrospinal fluid
      (CSF) composition. METHODS: Retrospective study (years 2001-2010) of clinical
      records and images and prospective follow-up (years 2010-2013) in 15 children (11
      girls, 4 boys; aged 5-16 years) diagnosed previously as "IIH", according to the
      criteria for pediatric IIH proposed by Rangwala, at four university pediatric
      centers in northern, central, and southern Italy. RESULTS: We identified six
      potential endocrine-metabolic comorbidities including, weight gain and obesity
      (n=5), recombinant growth hormone therapy (n=3), obesity and metabolic syndrome
      (n=1), secondary hyperaldosteronism (n=1), hypervitaminosis A (n=1), and
      corticosteroid therapy (n=1). Response to etiologically targeted treatments
      (e.g., spironolactone, octreotide) was documented. CONCLUSIONS: IIH is a protean
      syndrome caused by various potential (risk and) associative factors. Several
      conditions could influence the pressure regulation of CSF. An endocrine-metabolic
      altered homeostasis could be suggested in some IIH patients, and in this context,
      etiologically targeted therapies (spironolactone) should be considered.

PMID- 24025723
TI  - Metabolic rather than body composition measurements are associated with lower
      serum natriuretic peptide concentrations in normal weight and obese men.
AB  - BACKGROUND: Several studies have shown that obese persons have lower circulating
      natriuretic peptide (NP) concentrations. The cause of the relative NP deficiency
      seen in obese persons is poorly understood, although variation in body
      composition and metabolic abnormalities has been suggested to play a role. Thus,
      the aim of this study was to assess whether variation in circulating NP
      concentrations would be associated with differences in metabolic disturbances
      rather than with differences in body composition. METHODS: In 27 normal weight
      men (body mass index (BMI) = 20.0-24.9kg/m(2)) and 103 obese men (BMI >=
      30kg/m(2)), we determined body composition (total, android, and gynoid fat mass)
      by dual energy x-ray absorptiometry scanning, and we measured fasting serum
      concentrations of midregional proatrial NP (MR-proANP) and insulin, as well as
      fasting plasma glucose concentrations. RESULTS: Mean weight +/- SD was 74.9+/
      6.7kg in the normal weight men and 106.1+/-10.8kg in obese men. Applying multiple
      regressions, adjusting for age and weight status (normal weight vs. obese), serum
      MR-proANP concentrations were significantly inversely associated with serum
      insulin concentrations (beta = -0.39; P < 0.0001) and plasma glucose
      concentrations (beta = -0.21; P = 0.02) but not with total (beta = 0.00), android
      (beta = -0.01), or gynoid (beta = 0.03) fat mass percentage (P > 0.76). No
      significant interaction effects between metabolic measurements or body
      composition measurements and weight status on MR-proANP concentrations were found
      (P > 0.08). CONCLUSIONS: In normal weight and obese men, lower circulating NP
      concentrations are associated with higher insulin and glucose concentrations and
      not with the proportion of total fat mass or the distribution of fat mass.

PMID- 24025724
TI  - Vitamin D activates the Nrf2-Keap1 antioxidant pathway and ameliorates
      nephropathy in diabetic rats.
AB  - BACKGROUND: Diabetic nephropathy is a major risk of end-stage kidney disease.
      Many complex factors relate to the progression of diabetic nephropathy. Using
      nonobese type 2 diabetes model rats, we confirmed that oxidative stress was a
      crucial factor. Because recent studies suggest that vitamin D could suppress
      oxidative stress, we explored whether the active vitamin D analog, maxacalcitol,
      could also attenuate oxidative stress and prevent the progression of diabetic
      nephropathy. METHODS: Diabetic rats aged 20 weeks were divided into 3 groups and
      treated with insulin, maxacalcitol, and vehicle. At age 30 weeks, blood and urine
      analyses, renal histology, immunohistochemistry, real-time polymerase chain
      reaction, and western blot were performed. RESULTS: Although maxacalcitol reduced
      albuminuria and mesangial matrix expansion, no significant differences were
      observed in blood pressure and creatinine clearance among the 3 treatment groups.
      Systemic and intrarenal oxidative stress was reduced by maxacalcitol therapy.
      Expressions of nuclear factor-kappaB and nicotinamide adenine dinucleotide
      phosphate oxidase in the kidney also decreased in the insulin-treated and
      maxacalcitol-treated groups but increased in the vehicle-alone group. In
      addition, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)
      decreased and Kelch-like erythroid cell-derived protein with CNC homology (ECH)
      associated protein 1 (Keap1) increased in the vehicle-treated group; however,
      these expressions were restored in the maxacalcitol- and insulin-treated groups.
      CONCLUSIONS: It is suggested that maxacalcitol attenuates the progression of
      diabetic nephropathy by suppression of oxidative stress and amelioration of the
      Nrf2-Keap1 pathway in nonobese type 2 diabetes without significant changes in
      blood pressure and glomerular filtration rate.

PMID- 24025725
TI  - Resveratrol: therapeutic potential for improving cardiometabolic health.
AB  - BACKGROUND: Resveratrol, a natural polyphenol, has gained attention in recent
      years because of its connection with the health benefits of red wine and its
      anticancer activity in vitro. Studies in animal models have demonstrated
      beneficial effects on glucose metabolism, vascular function and anti-inflammatory
      and antioxidant properties. Human studies designed to understand the role of
      resveratrol in the prevention and treatment of age-related conditions such as
      diabetes, heart disease, and cancer have recently been undertaken. METHODS: We
      searched PubMed for original articles that reported studies of resveratrol in
      humans, using search terms, including resveratrol, human studies, glucose
      metabolism, vascular function, and inflammation. We also searched the reference
      lists of identified articles for additional papers and sought expert opinion on
      relevant studies. RESULTS: Resveratrol treatment has shown beneficial effects on
      glucose and lipid metabolism in some, but not all studies. Study population,
      resveratrol source, and dose have varied widely, potentially explaining
      inconsistent findings. Improvements were noted in endothelial function, systolic
      blood pressure, and markers of oxidative stress and inflammation in several
      studies. CONCLUSIONS: Despite the strong preclinical evidence of positive
      cardiometabolic effects, studies to date have not confirmed resveratrol's benefit
      in humans. Study variability and methodological issues limit interpretation of
      available results. Additional research, focusing on subjects with defined
      metabolic defects and using a range of doses, is needed to advance the field.

PMID- 24025727
TI  - A microscopic and macroscopic study of aging collagen on its molecular structure,
      mechanical properties, and cellular response.
AB  - During aging, collagen structure changes, detrimentally affecting tissues'
      biophysical and biomechanical properties due to an accumulation of advanced
      glycation end-products (AGEs). In this investigation, we conducted a parallel
      study of microscopic and macroscopic properties of different-aged collagens from
      newborn to 2-yr-old rats, to examine the effect of aging on fibrillogenesis,
      mechanical and contractile properties of reconstituted hydrogels from these
      collagens seeded with or without fibroblasts. In addition to fibrillogenesis of
      collagen under the conventional conditions, some fibrillogenesis was conducted
      alongside a 12-T magnetic field, and gelation rate and AGE content were measured.
      A nondestructive indentation technique and optical coherence tomography were used
      to determine the elastic modulus and dimensional changes, respectively. It was
      revealed that in comparison to younger specimens, older collagens exhibited
      higher viscosity, faster gelation rates, and a higher AGE-specific fluorescence.
      Exceptionally, only young collagens formed highly aligned fibrils under magnetic
      fields. The youngest collagen demonstrated a higher elastic modulus and
      contraction in comparison to the older collagen. We conclude that aging changes
      collagen monomer structure, which considerably affects the fibrillogenesis
      process, the architecture of the resulting collagen fibers and the global
      network, and the macroscopic properties of the formed constructs.

PMID- 24025726
TI  - Identification of potential synthetic lethal genes to p53 using a computational
      biology approach.
AB  - BACKGROUND: Identification of genes that are synthetic lethal to p53 is an
      important strategy for anticancer therapy as p53 mutations have been reported to
      occur in more than half of all human cancer cases. Although genome-wide RNAi
      screening is an effective approach to finding synthetic lethal genes, it is
      costly and labor-intensive. METHODS: To illustrate this approach, we identified
      potentially druggable genes synthetically lethal for p53 using three microarray
      datasets for gene expression profiles of the NCI-60 cancer cell lines, one next
      generation sequencing (RNA-Seq) dataset from the Cancer Genome Atlas (TCGA)
      project, and one gene expression data from the Cancer Cell Line Encyclopedia
      (CCLE) project. We selected the genes which encoded kinases and had significantly
      higher expression in the tumors with functional p53 mutations (somatic mutations)
      than in the tumors without functional p53 mutations as the candidates of
      druggable synthetic lethal genes for p53. We identified important regulatory
      networks and functional categories pertinent to these genes, and performed an
      extensive survey of literature to find experimental evidence that support the
      synthetic lethality relationships between the genes identified and p53. We also
      examined the drug sensitivity difference between NCI-60 cell lines with
      functional p53 mutations and NCI-60 cell lines without functional p53 mutations
      for the compounds that target the kinases encoded by the genes identified.
      RESULTS: Our results indicated that some of the candidate genes we identified had
      been experimentally verified to be synthetic lethal for p53 and promising targets
      for anticancer therapy while some other genes were putative targets for
      development of cancer therapeutic agents. CONCLUSIONS: Our study indicated that
      pre-screening of potential synthetic lethal genes using gene expression profiles
      is a promising approach for improving the efficiency of synthetic lethal RNAi
      screening.

PMID- 24025729
TI  - Integrated chromatin immunoprecipitation sequencing and microarray analysis
      identifies FOXA2 target genes in the glands of the mouse uterus.
AB  - Uterine glands and their secretions are indispensable for endometrial function
      and fertility; however, the mechanisms regulating their development and function
      are not well understood. Forkhead transcription factor box A2 (FOXA2) is uniquely
      expressed in the glandular epithelial (GE) cells of the uterus, and conditional
      deletion of Foxa2 after birth impedes uterine gland development. An integrative
      approach was used here to define the FOXA2 cistrome in the murine uterus. Genome
      wide mapping of FOXA2 binding sites was combined with transcriptomic analyses of
      isolated GE and Foxa2-deleted uteri. ChIP-Seq analyses found the number of FOXA2
      target genes was substantially greater in the adult (8893) than neonatal uterus
      (1101). In the neonatal uterus, FOXA2-bound and GE-expressed genes (469) were
      enriched for developmentally related processes, including cell cycle, cell
      junction, focal adhesion, and WNT signaling. In the adult uterus, FOXA2-bound and
      GE-expressed genes (3730) were enriched for functional processes, including
      metabolic pathways, focal adhesion, bacterial invasion of epithelial cells, and
      WNT signaling. Analysis of the uterine FOXA2 cistrome provides novel insights
      into mechanisms governing endometrial gland development and function, which are
      important to understand fundamental aspects of uterine differentiation,
      regeneration and disease.

PMID- 24025730
TI  - Diffusion and desorption of oxygen atoms on graphene.
AB  - To understand the reversible oxidation of graphene in a recent experiment, a
      density-functional theory study is performed. The adsorption energy of isolated
      oxygen atom on graphene is 2.3 eV, indicating a strong interaction between them.
      However, the migration barrier of oxygen atoms on graphene is only 0.8 eV and
      oxygen diffusion is still possible. Provided with this possibility, we find that,
      although a single oxygen atom is very difficult to desorb, cooperative desorption
      of two oxygen atoms is feasible. 

PMID- 24025728
TI  - Circadian clock function is disrupted by environmental tobacco/cigarette smoke,
      leading to lung inflammation and injury via a SIRT1-BMAL1 pathway.
AB  - Patients with obstructive lung diseases display abnormal circadian rhythms in
      lung function. We determined the mechanism whereby environmental
      tobacco/cigarette smoke (CS) modulates expression of the core clock gene BMAL1,
      through Sirtuin1 (SIRT1) deacetylase during lung inflammatory and injurious
      responses. Adult C57BL6/J and various mice mutant for SIRT1 and BMAL1 were
      exposed to both chronic (6 mo) and acute (3 and 10 d) CS, and we measured the
      rhythmic expression of clock genes, circadian rhythms of locomotor activity, lung
      function, and inflammatory and emphysematous responses in the lungs. CS exposure
      (100-300 mg/m(3) particulates) altered clock gene expression and reduced
      locomotor activity by disrupting the central and peripheral clocks and increased
      lung inflammation, causing emphysema in mice. BMAL1 was acetylated and degraded
      in the lungs of mice exposed to CS and in patients with chronic obstructive
      pulmonary disease (COPD), compared with lungs of the nonsmoking controls, linking
      it mechanistically to CS-induced reduction of SIRT1. Targeted deletion of Bmal1
      in lung epithelium augmented inflammation in response to CS, which was not
      attenuated by the selective SIRT1 activator SRT1720 (EC50=0.16 MUM) in these
      mice. Thus, the circadian clock, specifically the enhancer BMAL1 in epithelium,
      plays a pivotal role, mediated by SIRT1-dependent BMAL1, in the regulation of CS
      induced lung inflammatory and injurious responses.

PMID- 24025731
TI  - Vaccine acceptance: the UK perspective.
AB  - The United Kingdom has had a long history with vaccine acceptability dating back
      to Edward Jenner's theory of small pox vaccination. More recently, the
      discredited, Wakefield study published in 1998 continues to cause MMR skepticism.
      In pregnant women pertussis vaccination has been considerably more successful
      than influenza vaccination. Influenza vaccine uptake in healthcare workers
      remains poor. The media, politicians, and health reforms have contributed to the
      mixed coverage for these vaccines. In this article we examine vaccine
      acceptability from a UK perspective, and consider the future impact this is
      likely to have on the introduction of rotavirus and shingles vaccine in the UK in
      2013. 

PMID- 24025732
TI  - Identification of the Plasmodium berghei resistance locus 9 linked to survival on
      chromosome 9.
AB  - BACKGROUND: One of the main causes of mortality from severe malaria in Plasmodium
      falciparum infections is cerebral malaria (CM). An important host genetic
      component determines the susceptibility of an individual to develop CM or to
      clear the infection and become semi-immune. As such, the identification of
      genetic loci associated with susceptibility or resistance may serve to modulate
      disease severity. METHODOLOGY: The Plasmodium berghei mouse model for
      experimental cerebral malaria (ECM) reproduces several disease symptoms seen in
      human CM, and two different phenotypes, a susceptible (FVB/NJ) and a resistant
      mouse strain (DBA/2J), were examined. RESULTS: FVB/NJ mice died from infection
      within ten days, whereas DBA/2J mice showed a gender bias: males survived on
      average nineteen days and females either died early with signs of ECM or survived
      for up to three weeks. A comparison of brain pathology between FVB/NJ and DBA/2J
      showed no major differences with regard to brain haemorrhages or the number of
      parasites and CD3+ cells in the microvasculature. However, significant
      differences were found in the peripheral blood of infected mice: For example
      resistant DBA/2J mice had significantly higher numbers of circulating basophils
      than did FVB/NJ mice on day seven. Analysis of the F2 offspring from a cross of
      DBA/2J and FVB/NJ mice mapped the genetic locus of the underlying survival trait
      to chromosome 9 with a Lod score of 4.9. This locus overlaps with two previously
      identified resistance loci (char1 and pymr) from a blood stage malaria model.
      CONCLUSIONS: Survival best distinguishes malaria infections between FVB/NJ and
      DBA/2J mice. The importance of char1 and pymr on chromosome 9 in malaria
      resistance to P. berghei was confirmed. In addition there was an association of
      basophil numbers with survival.

PMID- 24025734
TI  - Condensed matter analogues of cosmology. Preface.

PMID- 24025733
TI  - An approach for differentiating echovirus 30 and Japanese encephalitis virus
      infections in acute meningitis/encephalitis: a retrospective study of 103 cases
      in Vietnam.
AB  - BACKGROUND: In recent decades, Echovirus 30 (E30) and Japanese encephalitis virus
      (JEV) have been reported to be the common causative agents of acute meningitis
      among patients in South East Asia. An E30 outbreak in Vietnam in 2001-2002 gained
      our interest because the initial clinical diagnosis of infected patients was due
      to JEV infection. There are few clinical insights regarding E30 cases, and there
      are no reports comparing E30 and JEV acute meningitis/encephalitis cases based on
      clinical symptoms and case histories. We therefore aimed to identify reliable
      clinical methods to differentiate E30 and JEV acute meningitis/encephalitis.
      METHODS: A retrospective, cross-sectional study was conducted to compare E30 and
      JEV acute meningitis/encephalitis cases. We collected and analyzed the clinical
      records of 43 E30 confirmed cases (E30 group) and 60 JEV confirmed cases (JEV
      group). Clinical data were compared between the E30 and the JEV groups.
      Differences of clinical parameters were analyzed by certain statistical tests.
      RESULTS: Fever, headache, and vomiting were the most common symptoms in both the
      E30 and the JEV groups. Combined symptoms of headache and vomiting and the triad
      of symptoms of fever, headache, and vomiting were observed in more patients in
      the E30 group (E30 vs. JEV: 19% vs. 0%, p < 0.001; 74% vs. 27%, p < 0.001,
      respectively). On the other hand, strong neurological symptoms such as seizure
      (5% vs. 73%, p < 0.001) and altered consciousness (12% vs. 97%, p < 0.001) were
      manifested primarily in the JEV group. CSF leukocytosis was observed
      predominantly in the E30 group (80 vs. 18 cells/MUL, p = 0.003), whereas
      decreasing CSF sugar level was observed predominantly in the JEV group (58.7 vs.
      46.9 mg/dL, p < 0.001). CONCLUSION: Fever, headache, vomiting, absence of
      neurological symptoms (seizure, altered consciousness), and presence of CSF
      leukocytosis are important parameters to consider in differentiating E30 from JEV
      cases during early infection. Then, proper measures can be adopted immediately to
      prevent the spread of the disease in the affected areas.

PMID- 24025735
TI  - Variable selection methods for developing a biomarker panel for prediction of
      dengue hemorrhagic fever.
AB  - BACKGROUND: The choice of selection methods to identify important variables for
      binary classification modeling is critical to produce stable models that are
      interpretable, that generate accurate predictions and have minimum bias. This
      work is motivated by data on clinical and laboratory features of severe dengue
      infections (dengue hemorrhagic fever, DHF) obtained from 51 individuals enrolled
      in a prospective observational study of acute human dengue infections. RESULTS:
      We carry out a comprehensive performance comparison using several classification
      models for DHF over the dengue data set. We compared variable selection results
      by Multivariate Adaptive Regression Splines, Learning Ensemble, Random Forest,
      Bayesian Moving Averaging, Stochastic Search Variable Selection, and Generalized
      Regularized Logistics Regression. Model averaging methods (bagging, boosting and
      ensemble learners) have higher accuracy, but the generalized regularized
      regression model has the highest predictive power because the linearity
      assumptions of candidate predictors are strongly satisfied via deviance chi
      square testing procedures. Bootstrapping applications for evaluating predictive
      regression coefficients in regularized regression model are performed.
      CONCLUSIONS: Feature reduction methods introduce inherent biases and therefore
      are data-type dependent. We propose that these limitations can be overcome using
      an exhaustive approach for searching feature space. Using this approach, our
      results suggest that IL-10, platelet and lymphocyte counts are the major features
      for predicting dengue DHF on the basis of blood chemistries and cytokine
      measurements.

PMID- 24025736
TI  - Biochemical and kinetic characterisation of a novel xylooligosaccharide
      upregulated GH43 beta-d-xylosidase/alpha-l-arabinofuranosidase (BXA43) from the
      probiotic Bifidobacterium animalis subsp. lactis BB-12.
AB  - The Bifidobacterium animalis subsp. lactis BB-12 gene BIF_00092, assigned to
      encode a beta-d-xylosidase (BXA43) of glycoside hydrolase family 43 (GH43), was
      cloned with a C-terminal His-tag and expressed in Escherichia coli. BXA43 was
      purified to homogeneity from the cell lysate and found to be a dual-specificity
      exo-hydrolase active on para-nitrophenyl-beta-d-xylopyranoside (pNPX), para
      nitrophenyl-alpha-L-arabinofuranoside (pNPA), beta-(1 -> 4)-xylopyranosyl
      oligomers (XOS) of degree of polymerisation (DP) 2-4, and birchwood xylan. A
      phylogenetic tree of the 92 characterised GH43 enzymes displayed five distinct
      groups (I - V) showing specificity differences. BXA43 belonged to group IV and
      had an activity ratio for pNPA:pNPX of 1:25. BXA43 was stable below 40 degrees C
      and at pH 4.0-8.0 and showed maximum activity at pH 5.5 and 50 degrees C. Km and
      kcat for pNPX were 15.6 +/- 4.2 mM and 60.6 +/- 10.8 s-1, respectively, and
      substrate inhibition became apparent above 18 mM pNPX. Similar kinetic parameters
      and catalytic efficiency values were reported for beta-d-xylosidase (XynB3) from
      Geobacillus stearothermophilus T-6 also belonging to group IV. The activity of
      BXA43 for xylooligosaccharides increased with the size and was 2.3 and 5.6 fold
      higher, respectively for xylobiose and xylotetraose compared to pNPX. BXA43
      showed clearly metal inhibition for Zn2+ and Ag+, which is different to its close
      homologues. Multiple sequence alignment and homology modelling indicated that
      Arg505Tyr506 present in BXA43 are probably important for binding to xylotetraose
      at subsite +3 and occur only in GH43 from the Bifidobacterium genus. 

PMID- 24025739
TI  - Sperm population structure and male fertility: an intraspecific study of sperm
      design and velocity in red deer.
AB  - Sperm design and velocity play key roles in influencing sperm performance and,
      therefore, can determine fertilization success. Several interspecific studies
      have demonstrated how these features correlate, and it has been hypothesized that
      selection may drive changes in these sperm traits. Here, we examine the
      association between sperm design and swimming velocity in a study conducted at an
      intraspecific level in Iberian red deer (Cervus elaphus hispanicus). We addressed
      how the structure of different sperm subpopulations, based on sperm morphometry
      and velocity, are interrelated and, in turn, how they associate with fertility.
      Our results show that males with high fertility rates have ejaculates with high
      percentages of spermatozoa exhibiting fast and linear movements and that these
      are highly correlated with a large proportion of spermatozoa having small and
      elongated heads. On the other hand, males with low fertility are characterized by
      a subpopulation structure in which slow and nonlinear as well as small and wide
      spermatozoa are predominant. These findings provide insight regarding how sperm
      size and velocity are interrelated and how they both are associated with
      fertility. 

PMID- 24025738
TI  - Uterine natural killer cells severely decrease in number at gestation day 6 in
      mice.
AB  - Uterine natural killer (uNK) cells remarkably increase in number after
      implantation. NK cells or their precursors migrate from the blood stream and
      contribute to the increase. However, the contribution of uNK cells present in the
      virgin uterus has been unclear. To elucidate this issue, we examined uterine
      leukocyte subsets during pregnancy in BALB/c mice. The most dramatic change was
      the massive decrease in CD11b- or Gr-1- cells at gestation day (gd) 6. Uterine NK
      cells at gd 0 were CD11b-, and severely decreased at gd 6. The decrease was
      selective, and the proportion of other cells examined did not decrease. Uterine
      NK cells almost recovered at gd 12. These cells at gd 12 were more mature and/or
      activated in terms of expression of CD11b, CD27, CD127, or B220 than at gd 0.
      CXCL12 expression was observed on uterine cells at gd 0 or 6, but not at gd 12,
      whereas CXCR4 was detected on uNK cells at gds 0 and 12. A much higher expression
      of IL-15 in uterine cells or interferon-gamma expression in uNK cells was
      observed at gd 12 than at gd 0. IL-15 receptor alpha chain was detected on uNK
      cells at gd 12, but not at gd 0. Taken together, these findings were consistent
      with our interpretation that uNK cells present at gd 0 do not contribute to the
      increase of uNK cell number after implantation, and NK cells or their precursors
      migrate into the uterus, mature, and produce interferon-gamma to support
      pregnancy.

PMID- 24025737
TI  - Maternal CD4+ and CD8+ T cell tolerance towards a fetal minor histocompatibility
      antigen in T cell receptor transgenic mice.
AB  - Tolerance of the maternal immune system in pregnancy is important for successful
      pregnancy because the semiallogeneic fetus may be subject to antifetal responses.
      We examined maternal tolerance to the fetus using a murine system in which a
      model paternally inherited antigen, ovalbumin (OVA), is expressed exclusively in
      the fetus and placenta. By employing T cell receptor (TCR) transgenic mice
      specific for major histocompatibility complex class I- or class II-restricted
      epitopes of OVA (OT-I and OT-II) as mothers, we investigated the fate of fetus
      specific CD8+ and CD4+ T cells, respectively, during gestation. Both OVA-specific
      CD8+ and CD4+ T cells displayed an activated phenotype in the peripheral lymphoid
      tissues of OVA-bred OT-I and OT-II mice, consistent with their encounter of fetal
      antigen. Whereas a small percentage of OVA-specific CD4+ T cells were deleted in
      the periphery and thymus of OVA-bred OT-II mice, with evidence of TCR
      downregulation in the remaining T cells, deletion and TCR downregulation were not
      observed in OVA-bred OT-I mice. Both CD4+ and CD8+ T cells upregulated inducible
      costimulator expression in response to the fetal antigen, but only CD4+ T cells
      consistently upregulated the inhibitory receptors programmed cell death 1 and
      cytotoxic T lymphocyte antigen-4. More regulatory T cells (Tregs) were present in
      pregnant OVA-bred than in WT-bred OT-II mice, revealing that Tregs expanded
      specifically in response to the fetal antigen. These data indicate that several
      mechanisms tolerize fetal antigen-specific maternal CD4+ T cells, whereas
      tolerance of fetal antigen-specific CD8+ T cells is less effective. The
      importance of these mechanisms is underscored by the finding that fetal loss
      occurs in OVA-bred OT-I but not OT-II mice.

PMID- 24025741
TI  - Cryopreservation of mouse spermatogonial stem cells in dimethylsulfoxide and
      polyethylene glycol.
AB  - Assisted reproductive techniques involving isolation, culture, and
      transplantation of spermatogonial stem cells (SSCs) have the potential to create
      transgenic livestock and to treat male infertility caused by cancer treatments
      such as chemotherapy or radiation. Because stem cells may need to be preserved
      for several years before reintroduction to the patients' testes, efficient SSC
      cryopreservation techniques need to be developed. SSCs can reinitiate
      spermatogenesis in recipient testes after freezing; however, optimal
      cryopreservation protocols have not been identified. The objective of this study
      was to develop an efficient cryopreservation method for SSCs using permeable
      cryoprotectant agents (PCAs) or additive cryoprotectant agents (ACAs). To
      identify an efficient cryopreservation method, populations of mouse testis cells
      enriched for SSCs were cultured in vitro and frozen using conventional freezing
      media containing various PCAs or ACAs for 1 wk or 1, 3, 6, 12, or 24 mo.
      Additionally, various molecular weights and concentrations of polyethylene glycol
      (PEG) were evaluated. Recovery rate, culture potential, and stem cell activity
      were significantly greater for cells frozen in 2.5% PEG with a molecular weight
      of 1000 compared to other treatment groups. These cells also retained the ability
      to colonize recipient testes, generate normal spermatogenesis, and contribute to
      viable offspring. The systematic analysis of many cryoprotectant agents indicates
      that 2.5% PEG (molecular weight 1000) is the most effective agent for efficient
      SSC cryopreservation. 

PMID- 24025740
TI  - Impact of vitrification on the meiotic spindle and components of the microtubule
      organizing center in mouse mature oocytes.
AB  - Cryopreservation of oocytes is becoming a valuable method for fertility
      preservation in women. However, various unphysiological alterations occur in the
      oocyte during the course of cryopreservation, one of which is the disappearance
      of the meiotic spindle. Fortunately, the meiotic spindle does regenerate after
      thawing the frozen oocytes, which enables completion of meiosis and further
      development after fertilization. Nonetheless, the mechanistic understanding of
      the meiotic spindle regeneration after cryopreservation is still scarce. Here, to
      gain insight into the mechanisms of the spindle disappearance and regeneration,
      we examined the status of spindle microtubules as well as the key components of
      the microtubule-organizing center (MTOC), specifically gamma-Tubulin, NEDD1, and
      Pericentrin, in mature (metaphase II) mouse oocytes at different steps of
      vitrification, a major cryopreservation technique. We found that the
      configuration of the spindle microtubules dynamically changed during the process
      of vitrification and that spindle regeneration was preceded by excessive
      microtubule polymerization, followed by reduction into the normal size and shape.
      Also, all three MTOC components exhibited disappearance and reappearance during
      the vitrification process, although Pericentrin appeared to regenerate in earlier
      steps compared to the other components. Furthermore, we found that the
      localization of the MTOC components to the spindle poles persisted even after
      depolymerization of spindle microtubules, suggesting that the MTOC components are
      impacted by vitrification independently from the integrity of the microtubules.
      The present study would set the stage for future investigations on the molecular
      mechanisms of the meiotic spindle regeneration, which may contribute to further
      improving protocols for oocyte cryopreservation. 

PMID- 24025743
TI  - Role of microRNA-136-3p on the expression of luteinizing hormone-human chorionic
      gonadotropin receptor mRNA in rat ovaries.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that interact with mRNAs and trigger
      either translation repression or RNA cleavage of target genes. In this study, we
      investigated whether miRNA was involved in down-regulation of the luteinizing
      hormone receptor (LHR) in rat ovaries. An miRNA microarray was used to analyze
      the overall miRNA expression profile of rat ovaries in association with the down
      regulation of LHR mRNA. We found that 23 miRNAs were highly expressed during this
      period. Combining these results with data from a bioinformatics database,
      clustering analysis led us to focus on miR-136-3p for further analysis. In both
      in vivo and in vitro studies, miR-136-3p expression levels were increased at 6 h
      after human chorionic gonadotropin (hCG) administration, concurrent with down
      regulation of LHR mRNA. Moreover, transfection of cultured granulosa cells with
      miR-136-3p resulted in a significant decrease in LHR mRNA levels in comparison
      with those of cells transfected with negative control. In contrast, transfection
      with a miR-136-3p inhibitor increased LHR mRNA levels. Finally, cotransfection of
      granulosa cells with a miR-136-3p inhibitor and a reporter vector containing the
      3'-untranslated region (UTR) of LHR mRNA and Renilla luciferase coding sequence
      revealed that miR-136-3p bound directly to the 3'-UTR of LHR mRNA. These data
      demonstrated that miR-136-3p participated in the down-regulation of LHR mRNA by
      binding directly to LHR mRNA. 

PMID- 24025742
TI  - Mouse strain does not influence the overall effects of bisphenol a-induced
      toxicity in adult antral follicles.
AB  - Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC) widely used in common
      consumer products containing polycarbonate plastics and epoxy resins. Previous
      studies indicate that other EDCs have species-dependent effects. Furthermore,
      some EDCs are known to have different effects in different strains within the
      same species. Little information, however, is known about whether the effects of
      BPA on the ovary differ by strain. Previous studies have shown that BPA inhibits
      follicle growth, induces atresia, and inhibits steroidogenesis and expression of
      steroidogenic enzymes in antral follicles from adult FVB mice. Thus, this study
      was designed to expand previous work by testing the hypothesis that mouse strain
      may differentially affect the susceptibility of adult antral follicles to BPA
      induced toxicity. To test this hypothesis, antral follicles were mechanically
      isolated from adult FVB, CD-1, and C57BL/6 mice, individually cultured for 6-120
      h and treated with either vehicle control (dimethylsulfoxide) or various
      concentrations of BPA (1.0 MUg/ml, 10 MUg/ml, or 100 MUg/ml). After culture,
      media were subjected to measurements of hormone production via ELISA, and
      follicles were subjected to real-time PCR for analysis of genes known to regulate
      steroidogenesis, the cell cycle, and atresia. Overall, BPA inhibited follicle
      growth and steroidogenesis in all tested strains, but CD-1 follicles were
      slightly more sensitive to BPA at early time points than FVB and C57BL/6
      follicles. These data suggest that CD-1, FVB, and C57BL/6 mice can all be used to
      investigate the effects of BPA on ovarian follicles. 

PMID- 24025744
TI  - The ciliary marginal zone (CMZ) in development and regeneration of the vertebrate
      eye.
AB  - The ciliary marginal zone (CMZ) is a circumferential ring of cells found at the
      extreme periphery of the maturing and mature neural retina that consists of
      retinal stem and progenitor cells. It functions to add retinal neurons to the
      periphery of the neural retina in larval and adult fish, larval frogs, and birds.
      Additionally, the CMZ may contribute to regeneration of the damaged retina in
      frogs and fish. In mammals, cells from the ciliary epithelium can be induced to
      express retinal stem cell-like characteristics in culture but may not comprise a
      classically defined CMZ. 

PMID- 24025746
TI  - Exact controllability of complex networks.
AB  - Controlling complex networks is of paramount importance in science and
      engineering. Despite the recent development of structural controllability theory,
      we continue to lack a framework to control undirected complex networks,
      especially given link weights. Here we introduce an exact controllability
      paradigm based on the maximum multiplicity to identify the minimum set of driver
      nodes required to achieve full control of networks with arbitrary structures and
      link-weight distributions. The framework reproduces the structural
      controllability of directed networks characterized by structural matrices. We
      explore the controllability of a large number of real and model networks, finding
      that dense networks with identical weights are difficult to be controlled. An
      efficient and accurate tool is offered to assess the controllability of large
      sparse and dense networks. The exact controllability framework enables a
      comprehensive understanding of the impact of network properties on
      controllability, a fundamental problem towards our ultimate control of complex
      systems. 

PMID- 24025747
TI  - Abstracts of the Third World Parkinson Congress. October 1-4, 2013. Montreal,
      Canada.

PMID- 24025748
TI  - Sindbis viral vectors transiently deliver tumor-associated antigens to lymph
      nodes and elicit diversified antitumor CD8+ T-cell immunity.
AB  - Tumors are theoretically capable of eliciting an antitumor immune response, but
      are often poorly immunogenic. Oncolytic viruses (OVs) have recently emerged as a
      promising strategy for the immunogenic delivery of tumor-associated antigens
      (TAAs) to cancer patients. However, safe and effective OV/TAA therapies have not
      yet been established. We have previously demonstrated that vectors based on
      Sindbis virus (SV) can inhibit tumor growth and activate the innate immune system
      in mice. Here, we demonstrate that SV vectors carrying a TAA generate a
      dramatically enhanced therapeutic effect in mice bearing subcutaneous,
      intraperitoneal, and lung cancers. Notably, SV/TAA efficacy was not dependent on
      tumor cell targeting, but was characterized by the transient expression of TAAs
      in lymph nodes draining the injection site. Early T-cell activation at this site
      was followed by a robust influx of NKG2D expressing antigen-specific cytotoxic
      CD8+ T cells into the tumor site, subsequently leading to the generation of long
      lasting memory T cells which conferred protection against rechallenge with TAA
      positive as well as TAA-negative tumor cells. By combining in vivo imaging, flow
      cytometry, cytotoxicity/cytokine assays, and tetramer analysis, we investigated
      the relationship between these events and propose a model for CD8+ T-cell
      activation during SV/TAA therapy.

PMID- 24025745
TI  - The reuniens and rhomboid nuclei: neuroanatomy, electrophysiological
      characteristics and behavioral implications.
AB  - The reuniens and rhomboid nuclei, located in the ventral midline of the thalamus,
      have long been regarded as having non-specific effects on the cortex, while other
      evidence suggests that they influence behavior related to the photoperiod,
      hunger, stress or anxiety. We summarise the recent anatomical,
      electrophysiological and behavioral evidence that these nuclei also influence
      cognitive processes. The first part of this review describes the reciprocal
      connections of the reuniens and rhomboid nuclei with the medial prefrontal cortex
      and the hippocampus. The connectivity pattern among these structures is
      consistent with the idea that these ventral midline nuclei represent a nodal hub
      to influence prefrontal-hippocampal interactions. The second part describes the
      effects of a stimulation or blockade of the ventral midline thalamus on cortical
      and hippocampal electrophysiological activity. The final part summarizes recent
      literature supporting the emerging view that the reuniens and rhomboid nuclei may
      contribute to learning, memory consolidation and behavioral flexibility, in
      addition to general behavior and aspects of metabolism. 

PMID- 24025749
TI  - In vitro and in vivo efficacy of SYL040012, a novel siRNA compound for treatment
      of glaucoma.
AB  - Glaucoma is a progressive ocular syndrome characterized by degeneration of the
      optic nerve and irreversible visual field loss. Elevated intraocular pressure
      (IOP) is the main risk factor for glaucoma. Increased IOP is the result of an
      imbalance between synthesis and outflow of aqueous humor (AH). Blocking beta2
      adrenergic receptor (ADRB2) has shown to reduce IOP by decreasing production of
      AH at the ciliary body (CB). SYL040012 is a siRNA designed to specifically
      silence ADRB2 currently under development for glaucoma treatment. Here, we show
      that SYL040012 specifically reduces ADRB2 expression in cell cultures and eye
      tissues. The compound enters the eye shortly after administration in eye drops
      and is rapidly distributed among structures of the anterior segment of the eye.
      In addition, SYL040012 is actively taken up by cells of the CB but not by cells
      of systemic organs such as the lungs, where inhibition of ADRB2 could cause
      undesirable side effects. Moreover, SYL040012 reduces IOP in normotensive and
      hypertensive animal models and the effect appears to be long lasting and
      extremely well tolerated both locally and systemically. 

PMID- 24025750
TI  - An efficient antiviral strategy for targeting hepatitis B virus genome using
      transcription activator-like effector nucleases.
AB  - The hepatitis B virus (HBV) is a DNA virus that can cause chronic hepatitis B
      (CHB) in humans. Current therapies for CHB infection are limited in efficacy and
      do not target the pre-existing viral genomic DNA, which are present in the
      nucleus as a covalently closed circular DNA (cccDNA) form. The transcription
      activator-like (TAL) effector nucleases (TALENs) are newly developed enzymes that
      can cleave sequence-specific DNA targets. Here, TALENs targeting the conserved
      regions of the viral genomic DNA among different HBV genotypes were constructed.
      The expression of TALENs in Huh7 cells transfected with monomeric linear full
      length HBV DNA significantly reduced the viral production of HBeAg, HBsAg, HBcAg,
      and pgRNA, resulted in a decreased cccDNA level and misrepaired cccDNAs without
      apparent cytotoxic effects. The anti-HBV effect of TALENs was further
      demonstrated in a hydrodynamic injection-based mouse model. In addition, an
      enhanced antiviral effect with combinations of TALENs and interferon-alpha (IFN
      alpha) treatment was observed and expression of TALENs restored HBV suppressed
      IFN-stimulated response element-directed transcription. Taken together, these
      data indicate that TALENs can specifically target and successfully inactivate the
      HBV genome and are potently synergistic with IFN-alpha, thus providing a
      potential therapeutic strategy for treating CHB infection. 

PMID- 24025751
TI  - Targeting intestinal inflammation with CD98 siRNA/PEI-loaded nanoparticles.
AB  - Intestinal CD98 expression plays a crucial role in controlling homeostatic and
      innate immune responses in the gut. Modulation of CD98 expression in intestinal
      cells therefore represents a promising therapeutic strategy for the treatment and
      prevention of inflammatory intestinal diseases, such as inflammatory bowel
      disease. Here, the advantages of nanoparticles (NPs) are used, including their
      ability to easily pass through physiological barriers and evade phagocytosis,
      high loading concentration, rapid kinetics of mixing and resistance to
      degradation. Using physical chemistry characterizations techniques, CD98
      siRNA/polyethyleneimine (PEI)-loaded NPs was characterized (diameter of ~480 nm
      and a zeta potential of -5.26 mV). Interestingly, CD98 siRNA can be
      electrostatically complexed by PEI and thus protected from RNase. In addition,
      CD98 siRNA/PEI-loaded NPs are nontoxic and biocompatible with intestinal cells.
      Oral administration of CD98/PEI-loaded NPs encapsulated in a hydrogel reduced
      CD98 expression in mouse colonic tissues and decreased dextran sodium sulfate
      induced colitis in a mouse model. Finally, flow cytometry showed that CD98 was
      effectively downregulated in the intestinal epithelial cells and intestinal
      macrophages of treated mice. Finally, the results collectively demonstrated the
      therapeutic effect of "hierarchical nano-micro particles" with colon-homing
      capabilities and the ability to directly release "molecularly specific" CD98
      siRNA in colonic cells, thereby decreasing colitis. 

PMID- 24025752
TI  - Phase I clinical trial of SYL040012, a small interfering RNA targeting beta
      adrenergic receptor 2, for lowering intraocular pressure.
AB  - The objective of this study was to evaluate ocular tolerance, safety, and effect
      on intraocular pressure (IOP) of a topically administered small interfering RNA;
      SYL040012, on healthy volunteers. The study was an open-label, controlled, single
      center study comprised of two intervals that enrolled 30 healthy subjects having
      IOP below 21 mmHg. SYL040012 was administered to one eye as a single dose to six
      subjects during interval 1. During interval 2 two different doses of SYL040012
      were administered to one eye on a daily basis to two separate groups of 12
      subjects each, over a period of 7 days. The contralateral eye was evaluated but
      not administered and served as control for the tolerance study. SYL040012 was
      well tolerated locally. No local or systemic adverse events related to the
      product developed in response to any of the doses studied. SYL040012 was not
      detected in plasma at any time point. Administration of SYL040012 over a period
      of 7 days reduced IOP values in 15 out of 24 healthy subjects regardless of the
      dose used. IOP decrease was statistically significant in response to one of the
      doses tested and responsiveness to SYL040012 seemed to be greater in individuals
      with higher baseline IOP. 

PMID- 24025753
TI  - Levels of circulating neopterin in patients with severe carotid artery stenosis
      undergoing carotid stenting.
AB  - AIMS: The association between an elevated serum neopterin level and the
      development of coronary artery complex lesions has been extensively assessed;
      however, the correlation between the serum neopterin level and the development of
      carotid artery stenosis has seldom been reported. This study tested whether this
      biomarker is increased in patients with severe carotid artery stenosis(>=70%)
      undergoing carotid artery(CA) stenting and investigated independent predictors of
      an increased circulating neopterin level. METHODS: Fifty patients with severe CA
      stenosis(CAS) undergoing CA stenting were consecutively enrolled in this study
      from January 2009 through December 2011. The serum neopterin levels of age- and
      gender-matched acute ischemic stroke(AIS) patients(n=120) and control
      subjects(CS)(n=33) were also measured. A blood sample was prospectively collected
      from each patient in the catheterization room. RESULTS: The serum levels of
      neopterin were significantly higher in the CAS patients than in the AIS patients
      or CS and significantly higher in the AIS patients than in the CS(all p<0.001).
      An analysis of the variables of 170 patients(CAS+AIS) demonstrated that age, a
      previous history of stroke and severe CAS were significantly correlated with an
      increased serum level of neopterin(all p<0.005). A multivariate binary logistic
      regression analysis of the severe CAS patients(n=50) demonstrated that age and
      the creatinine level were independent predictors of a high neopterin
      level(neopterin level >=16.52 ng/dL, i.e., according to the median value of
      neopterin)(all p<0.05). CONCLUSIONS: The circulating neopterin levels are
      significantly higher in patients with severe CAS than in those with AIS. The
      presence of CAS, age and the creatinine level were significantly correlated with
      an increased serum neopterin level.

PMID- 24025754
TI  - National, state, and local area vaccination coverage among children aged 19-35
      months - United States, 2012.
AB  - The National Immunization Survey (NIS) is a random-digit-dialed telephone survey
      used to monitor vaccination coverage among U.S. children aged 19-35 months. This
      report describes national, state, and selected local area vaccination coverage
      estimates for children born during January 2009-May 2011, based on results from
      the 2012 NIS. Healthy People 2020* objectives set childhood vaccination targets
      of 90% for >=1 doses of measles, mumps, and rubella vaccine (MMR); >=3 doses of
      hepatitis B vaccine (HepB); >=3 doses of poliovirus vaccine; >=1 doses of
      varicella vaccine; >=4 doses of diphtheria, tetanus, and pertussis vaccine
      (DTaP); >=4 doses of pneumococcal conjugate vaccine (PCV); and the full series of
      Haemophilus influenzae type b vaccine (Hib). Vaccination coverage remained near
      or above the national Healthy People 2020 target for >=1 doses of MMR (90.8%),
      >=3 doses of poliovirus vaccine (92.8%), >=3 doses of HepB (89.7%), and >=1 doses
      of varicella vaccine (90.2%). Coverage increased from 68.6% in 2011 to 71.6% in
      2012 for the birth dose of HepB.? Coverage was below the Healthy People 2020
      target and either decreased or remained stable relative to 2011 for >=4 doses of
      DTaP (82.5%), the full series of Hib (80.9%), and >=4 doses of PCV (81.9%).
      Coverage also remained stable relative to 2011 and below the Healthy People 2020
      targets of 85% and 80%, respectively, for >=2 doses of hepatitis A vaccine (HepA)
      (53.0%), and rotavirus vaccine (68.6%). The percentage of children who had not
      received any vaccinations remained <1.0%. Although disparities in coverage were
      not observed for most racial/ethnic groups, children living in families with
      incomes below the federal poverty level had lower coverage than children living
      in families at or above the poverty level for >=4 doses of DTaP (by 6.5
      percentage points), the full Hib series (by 7.6 percentage points), >=4 doses of
      PCV (by 8.6 percentage points), >=2 doses of HepA (by 6.0 percentage points), and
      rotavirus vaccine (by 9.5 percentage points). Maintaining high coverage levels is
      important to maintain the current low burden of vaccine-preventable diseases in
      the United States and prevent their resurgence. 

PMID- 24025755
TI  - Measles - United States, January 1-August 24, 2013.
AB  - Measles is a highly contagious, acute viral illness that can lead to
      complications and death. Although measles elimination (i.e., interruption of
      continuous transmission lasting >=12 months) was declared in the United States in
      2000, importation of measles cases continues to occur. During 2001-2012, the
      median annual number of measles cases reported in the United States was 60
      (range: 37-220), including 26 imported cases (range: 18-80). The median annual
      number of outbreaks reported to CDC was four (range: 2-16). Since elimination,
      the highest numbers of U.S. cases were reported in 2008 (140 cases) and 2011
      (220). To update measles data, CDC evaluated cases reported by 16 states during
      January 1-August 24, 2013. A total of 159 cases of measles were reported during
      this period. Most cases were in persons who were unvaccinated (131 [82%]) or had
      unknown vaccination status (15 [9%]). Forty-two importations were reported, and
      21(50%) were importations from the World Health Organization (WHO) European
      Region. Eight outbreaks accounted for 77% of the cases reported in 2013,
      including the largest outbreak reported in the United States since 1996 (58
      cases). These outbreaks demonstrate that unvaccinated persons place themselves
      and their communities at risk for measles and that high vaccination coverage is
      important to prevent the spread of measles after importation. 

PMID- 24025756
TI  - Influenza vaccination practices of physicians and caregivers of children with
      neurologic and neurodevelopmental conditions - United States, 2011-12 influenza
      season.
AB  - Cognitive dysfunction, seizure disorders (epilepsy), and other neurologic
      disorders are conditions associated with a high risk for complications of
      influenza virus infection. This risk was observed during the 2009 influenza
      pandemic; among 336 pediatric deaths, 146 occurred in children with underlying
      neurologic disorders, most commonly intellectual disability (76%) and epilepsy
      (51%). Because little is known about influenza-related knowledge and practices
      among the families and health-care providers of children with neurologic or
      neurodevelopmental (NND) conditions, CDC worked with Family Voices and the
      American Academy of Pediatrics to survey parents and physicians during the 2011
      12 influenza season to assess these factors. Among 1,005 children with NND
      conditions, parents reported that 50% of children were vaccinated or had a
      vaccine appointment scheduled. Vaccination rates were low for children with
      intellectual disability (52%) and epilepsy (59%). Physician recognition of high
      risk conditions was low for intellectual disability (46%) and epilepsy (52%).
      Efforts to improve physician awareness are essential because physicians are in a
      key position to educate parents of children with NND conditions about their
      increased risk for influenza complications and the importance of prevention
      through vaccination. Further research also is needed to identify barriers to
      influenza vaccination among families and health-care providers of these children.

PMID- 24025757
TI  - Comparison of provisional with final notifiable disease case counts - National
      Notifiable Diseases Surveillance System, 2009.
AB  - States report notifiable disease cases to CDC through the National Notifiable
      Diseases Surveillance System (NNDSS). This allows CDC to assist with public
      health action and monitor infectious diseases across jurisdictional boundaries
      nationwide. The Morbidity and Mortality Weekly Report (MMWR) is used to
      disseminate these data on infectious disease incidence. The extent to which the
      weekly notifiable conditions are overreported or underreported can affect public
      health understanding of changes in the burden, distribution, and trends in
      disease, which is essential for control of communicable diseases. NNDSS
      encourages state health departments to notify CDC of a case when initially
      reported. These cases are included in the weekly provisional counts. The status
      of reported cases can change after further investigation by the states, resulting
      in differences between provisional and final counts. Increased knowledge of these
      differences can help in guiding the use of information from NNDSS. To quantify
      the extent to which final counts differ from provisional counts of notifiable
      infectious disease in the United States, CDC analyzed 2009 NNDSS data for 67
      conditions. The results of this analysis demonstrate that for five conditions,
      final case counts were lower than provisional counts, but for 59 conditions,
      final counts were higher than provisional counts. The median difference between
      final and provisional counts was 16.7%; differences were <=20% for 39 diseases
      but >50% for 12. These differences occur for various diseases and in all states.
      Provisional case counts should be interpreted with caution and an understanding
      of the reporting process. 

PMID- 24025759
TI  - Notes from the field: measles outbreak associated with a traveler returning from
      India - North Carolina, April-May 2013.
AB  - On April 14, 2013, public health officials in North Carolina were notified of
      suspected measles infections in two unvaccinated members of a family. Measles was
      confirmed by laboratory testing at the State Laboratory of Public Health on April
      16, 2013. Investigators learned that a third unvaccinated member of the household
      had developed fever and rash 11 days earlier, after returning to the United
      States from a 3-month visit to India, but measles had not been suspected until
      household contacts sought evaluation for similar symptoms. 

PMID- 24025758
TI  - Notes from the field: measles outbreak among members of a religious community -
      Brooklyn, New York, March-June 2013.
AB  - On March 13, 2013, an intentionally unvaccinated adolescent aged 17 years
      returned to New York City from London, United Kingdom, while infectious with
      measles. This importation led to the largest outbreak of measles in the United
      States since 1996. 

PMID- 24025760
TI  - Electrocortical processing of social signals of threat in combat-related post
      traumatic stress disorder.
AB  - Post-traumatic stress disorder (PTSD) is characterized by avoidance, emotional
      numbing, increased arousal and hypervigilance for threat following a trauma.
      Thirty-three veterans (19 with PTSD, 14 without PTSD) who had experienced combat
      trauma while on deployment in Iraq and/or Afghanistan completed an emotional
      faces matching task while electroencephalography was recorded. Vertex positive
      potentials (VPPs) elicited by happy, angry and fearful faces were smaller in
      veterans with versus without PTSD. In addition, veterans with PTSD exhibited
      smaller late positive potentials (LPPs) to angry faces and greater intrusive
      symptoms predicted smaller LPPs to fearful faces in the PTSD group. Veterans with
      PTSD were also less accurate at identifying angry faces, and accuracy decreased
      in the PTSD group as hyperarousal symptoms increased. These findings show reduced
      early processing of emotional faces, irrespective of valence, and blunted
      prolonged processing of social signals of threat in conjunction with impaired
      perception for angry faces in PTSD. 

PMID- 24025763
TI  - A hybrid density functional view of native vacancies in gallium nitride.
AB  - We investigated the transition energy levels of the vacancy defects in gallium
      nitride by means of a hybrid density functional theory approach (DFT). We show
      that, in contrast to predictions from a recent study on the level of purely local
      DFT, the inclusion of screened exchange stabilizes the triply positive charge
      state of the nitrogen vacancy for Fermi energies close to the valence band. On
      the other hand, the defect levels associated with the negative charge states of
      the nitrogen vacancy hybridize with the conduction band and turn out to be
      energetically unfavorable, except for high n-doping. For the gallium vacancy, the
      increased magnetic splitting between up-spin and down-spin bands due to stronger
      exchange interactions in sX-LDA pushes the defect levels deeper into the band gap
      and significantly increases the associated charge transition levels. Based on
      these results, we propose the epsilon(0| - 1) transition level as an alternative
      candidate for the yellow luminescence in GaN. 

PMID- 24025762
TI  - Engineering of cofactor regeneration enhances (2S,3S)-2,3-butanediol production
      from diacetyl.
AB  - (2S,3S)-2,3-Butanediol ((2S,3S)-2,3-BD) is a potentially valuable liquid fuel and
      an excellent building block in asymmetric synthesis. In this study, cofactor
      engineering was applied to improve the efficiency of (2S,3S)-2,3-BD production
      and simplify the product purification. Two NADH regeneration enzymes, glucose
      dehydrogenase and formate dehydrogenase (FDH), were introduced into Escherichia
      coli with 2,3-BD dehydrogenase, respectively. Introduction of FDH resulted in
      higher (2S,3S)-2,3-BD concentration, productivity and yield from diacetyl, and
      large increase in the intracellular NADH concentration. In fed-batch
      bioconversion, the final titer, productivity and yield of (2S,3S)-2,3-BD on
      diacetyl reached 31.7 g/L, 2.3 g/(L.h) and 89.8%, the highest level of (2S,3S)
      2,3-BD production thus far. Moreover, cosubstrate formate was almost totally
      converted to carbon dioxide and no organic acids were produced. The biocatalytic
      process presented should be a promising route for biotechnological production of
      NADH-dependent microbial metabolites. 

PMID- 24025764
TI  - Propofol impairs spatial memory consolidation and prevents learning-induced
      increase in hippocampal matrix metalloproteinase-9 levels in rat.
AB  - The specific impact of propofol on memory consolidation remains controversial.
      Matrix metalloproteinase-9 (MMP-9) has been shown to be critical for modulation
      of long-lasting synaptic plasticity that is necessary for memory consolidation.
      We therefore sought to examine whether post-training propofol affects Morris
      water maze performance and subsequent MMP-9 expression in the hippocampus. Our
      results indicate that post-training administration of 150 mg/kg propofol but not
      75 mg/kg propofol disrupts spatial memory retention 24 h after training. In
      addition, Morris water maze training induced a gradual increase in levels of pro
      MMP-9 and active-MMP-9, which were attenuated by 150 mg/kg propofol but not 75
      mg/kg propofol treatment immediately after training. Collectively, these findings
      indicate that the amnesic effect of propofol stems at least partially from its
      impairment of memory consolidation, which parallels with reduced activity of
      hippocampal MMP-9. 

PMID- 24025765
TI  - Differential expression of miR-195 in esophageal squamous cell carcinoma and miR
      195 expression inhibits tumor cell proliferation and invasion by targeting of
      Cdc42.
AB  - MicroRNAs (miRNA) have played an important role in carcinogenesis. In this study,
      Agilent miRNA microarray was used to identify differentially expressed miRNAs in
      esophageal squamous cell carcinoma (ESCC) tissues and miR-195 was downregulated
      in ESCC compared with normal esophageal tissues. Moreover, Cdc42 was confirmed as
      target gene of miR-195. Ectopic expression of miR-195 in ESCC cells significantly
      downregulated Cdc42 by directly binding its 3' untranslated regions, and induced
      G1 cell cycle arrest, leading to a significant decrease in cell growth,
      migration, and invasion in vitro. Therefore, our findings demonstrated that miR
      195 may act as a tumor suppressor in ESCC by targeting Cdc42. 

PMID- 24025766
TI  - Materials science: Fast-track solar cells.

PMID- 24025767
TI  - Usp16 contributes to somatic stem-cell defects in Down's syndrome.
AB  - Down's syndrome results from full or partial trisomy of chromosome 21. However,
      the consequences of the underlying gene-dosage imbalance on adult tissues remain
      poorly understood. Here we show that in Ts65Dn mice, which are trisomic for 132
      genes homologous to genes on human chromosome 21, triplication of Usp16 reduces
      the self-renewal of haematopoietic stem cells and the expansion of mammary
      epithelial cells, neural progenitors and fibroblasts. In addition, Usp16 is
      associated with decreased ubiquitination of Cdkn2a and accelerated senescence in
      Ts65Dn fibroblasts. Usp16 can remove ubiquitin from histone H2A on lysine 119, a
      critical mark for the maintenance of multiple somatic tissues. Downregulation of
      Usp16, either by mutation of a single normal Usp16 allele or by short interfering
      RNAs, largely rescues all of these defects. Furthermore, in human tissues
      overexpression of USP16 reduces the expansion of normal fibroblasts and postnatal
      neural progenitors, whereas downregulation of USP16 partially rescues the
      proliferation defects of Down's syndrome fibroblasts. Taken together, these
      results suggest that USP16 has an important role in antagonizing the self-renewal
      and/or senescence pathways in Down's syndrome and could serve as an attractive
      target to ameliorate some of the associated pathologies. 

PMID- 24025768
TI  - Pif1 helicase and Poldelta promote recombination-coupled DNA synthesis via bubble
      migration.
AB  - During DNA repair by homologous recombination (HR), DNA synthesis copies
      information from a template DNA molecule. Multiple DNA polymerases have been
      implicated in repair-specific DNA synthesis, but it has remained unclear whether
      a DNA helicase is involved in this reaction. A good candidate DNA helicase is
      Pif1, an evolutionarily conserved helicase in Saccharomyces cerevisiae important
      for break-induced replication (BIR) as well as HR-dependent telomere maintenance
      in the absence of telomerase found in 10-15% of all cancers. Pif1 has a role in
      DNA synthesis across hard-to-replicate sites and in lagging-strand synthesis with
      polymerase delta (Poldelta). Here we provide evidence that Pif1 stimulates DNA
      synthesis during BIR and crossover recombination. The initial steps of BIR occur
      normally in Pif1-deficient cells, but Poldelta recruitment and DNA synthesis are
      decreased, resulting in premature resolution of DNA intermediates into half
      crossovers. Purified Pif1 protein strongly stimulates Poldelta-mediated DNA
      synthesis from a D-loop made by the Rad51 recombinase. Notably, Pif1 liberates
      the newly synthesized strand to prevent the accumulation of topological
      constraint and to facilitate extensive DNA synthesis via the establishment of a
      migrating D-loop structure. Our results uncover a novel function of Pif1 and
      provide insights into the mechanism of HR. 

PMID- 24025769
TI  - Stem cells: Down's syndrome link to ageing.

PMID- 24025771
TI  - Stem cells: Reprogramming in situ.

PMID- 24025770
TI  - Immune clearance of highly pathogenic SIV infection.
AB  - Established infections with the human and simian immunodeficiency viruses (HIV
      and SIV, respectively) are thought to be permanent with even the most effective
      immune responses and antiretroviral therapies only able to control, but not
      clear, these infections. Whether the residual virus that maintains these
      infections is vulnerable to clearance is a question of central importance to the
      future management of millions of HIV-infected individuals. We recently reported
      that approximately 50% of rhesus macaques (RM; Macaca mulatta) vaccinated with
      SIV protein-expressing rhesus cytomegalovirus (RhCMV/SIV) vectors manifest
      durable, aviraemic control of infection with the highly pathogenic strain
      SIVmac239 (ref. 5). Here we show that regardless of the route of challenge,
      RhCMV/SIV vector-elicited immune responses control SIVmac239 after demonstrable
      lymphatic and haematogenous viral dissemination, and that replication-competent
      SIV persists in several sites for weeks to months. Over time, however, protected
      RM lost signs of SIV infection, showing a consistent lack of measurable plasma-
      or tissue-associated virus using ultrasensitive assays, and a loss of T-cell
      reactivity to SIV determinants not in the vaccine. Extensive ultrasensitive
      quantitative PCR and quantitative PCR with reverse transcription analyses of
      tissues from RhCMV/SIV vector-protected RM necropsied 69-172 weeks after
      challenge did not detect SIV RNA or DNA sequences above background levels, and
      replication-competent SIV was not detected in these RM by extensive co-culture
      analysis of tissues or by adoptive transfer of 60 million haematolymphoid cells
      to naive RM. These data provide compelling evidence for progressive clearance of
      a pathogenic lentiviral infection, and suggest that some lentiviral reservoirs
      may be susceptible to the continuous effector memory T-cell-mediated immune
      surveillance elicited and maintained by cytomegalovirus vectors. 

PMID- 24025772
TI  - Migrating bubble during break-induced replication drives conservative DNA
      synthesis.
AB  - The repair of chromosomal double strand breaks (DSBs) is crucial for the
      maintenance of genomic integrity. However, the repair of DSBs can also
      destabilize the genome by causing mutations and chromosomal rearrangements, the
      driving forces for carcinogenesis and hereditary diseases. Break-induced
      replication (BIR) is one of the DSB repair pathways that is highly prone to
      genetic instability. BIR proceeds by invasion of one broken end into a homologous
      DNA sequence followed by replication that can copy hundreds of kilobases of DNA
      from a donor molecule all the way through its telomere. The resulting repaired
      chromosome comes at a great cost to the cell, as BIR promotes mutagenesis, loss
      of heterozygosity, translocations, and copy number variations, all hallmarks of
      carcinogenesis. BIR uses most known replication proteins to copy large portions
      of DNA, similar to S-phase replication. It has therefore been suggested that BIR
      proceeds by semiconservative replication; however, the model of a bona fide,
      stable replication fork contradicts the known instabilities associated with BIR
      such as a 1,000-fold increase in mutation rate compared to normal replication.
      Here we demonstrate that in budding yeast the mechanism of replication during BIR
      is significantly different from S-phase replication, as it proceeds via an
      unusual bubble-like replication fork that results in conservative inheritance of
      the new genetic material. We provide evidence that this atypical mode of DNA
      replication, dependent on Pif1 helicase, is responsible for the marked increase
      in BIR-associated mutations. We propose that the BIR mode of synthesis presents a
      powerful mechanism that can initiate bursts of genetic instability in eukaryotes,
      including humans. 

PMID- 24025773
TI  - Reprogramming in vivo produces teratomas and iPS cells with totipotency features.
AB  - Reprogramming of adult cells to generate induced pluripotent stem cells (iPS
      cells) has opened new therapeutic opportunities; however, little is known about
      the possibility of in vivo reprogramming within tissues. Here we show that
      transitory induction of the four factors Oct4, Sox2, Klf4 and c-Myc in mice
      results in teratomas emerging from multiple organs, implying that full
      reprogramming can occur in vivo. Analyses of the stomach, intestine, pancreas and
      kidney reveal groups of dedifferentiated cells that express the pluripotency
      marker NANOG, indicative of in situ reprogramming. By bone marrow
      transplantation, we demonstrate that haematopoietic cells can also be
      reprogrammed in vivo. Notably, reprogrammable mice present circulating iPS cells
      in the blood and, at the transcriptome level, these in vivo generated iPS cells
      are closer to embryonic stem cells (ES cells) than standard in vitro generated
      iPS cells. Moreover, in vivo iPS cells efficiently contribute to the
      trophectoderm lineage, suggesting that they achieve a more plastic or primitive
      state than ES cells. Finally, intraperitoneal injection of in vivo iPS cells
      generates embryo-like structures that express embryonic and extraembryonic
      markers. We conclude that reprogramming in vivo is feasible and confers
      totipotency features absent in standard iPS or ES cells. These discoveries could
      be relevant for future applications of reprogramming in regenerative medicine. 

PMID- 24025774
TI  - The maize Galpha gene COMPACT PLANT2 functions in CLAVATA signalling to control
      shoot meristem size.
AB  - Shoot growth depends on meristems, pools of stem cells that are maintained by a
      negative feedback loop between the CLAVATA pathway and the WUSCHEL homeobox gene.
      CLAVATA signalling involves a secreted peptide, CLAVATA3 (CLV3), and its
      perception by cell surface leucine-rich repeat (LRR) receptors, including the
      CLV1 receptor kinase and a LRR receptor-like protein, CLV2 (ref. 4). However, the
      signalling mechanisms downstream of these receptors are poorly understood,
      especially for LRR receptor-like proteins, which lack a signalling domain. Here
      we show that maize COMPACT PLANT2 (CT2) encodes the predicted alpha-subunit
      (Galpha) of a heterotrimeric GTP binding protein. Maize ct2 phenotypes resemble
      Arabidopsis thaliana clavata mutants, and genetic, biochemical and functional
      assays indicate that CT2/Galpha transmits a stem-cell-restrictive signal from a
      CLAVATA LRR receptor, suggesting a new function for Galpha signalling in plants.
      Heterotrimeric GTP-binding proteins are membrane-associated molecular switches
      that are commonly activated by ligand binding to an associated seven-pass
      transmembrane (7TM) G-protein-coupled receptor (GPCR). Recent studies have
      questioned the idea that plant heterotrimeric G proteins interact with canonical
      GPCRs, and our findings suggest that single pass transmembrane receptors act as
      GPCRs in plants, challenging the dogma that GPCRs are exclusively 7TM proteins. 

PMID- 24025775
TI  - Efficient planar heterojunction perovskite solar cells by vapour deposition.
AB  - Many different photovoltaic technologies are being developed for large-scale
      solar energy conversion. The wafer-based first-generation photovoltaic devices
      have been followed by thin-film solid semiconductor absorber layers sandwiched
      between two charge-selective contacts and nanostructured (or mesostructured)
      solar cells that rely on a distributed heterojunction to generate charge and to
      transport positive and negative charges in spatially separated phases. Although
      many materials have been used in nanostructured devices, the goal of attaining
      high-efficiency thin-film solar cells in such a way has yet to be achieved.
      Organometal halide perovskites have recently emerged as a promising material for
      high-efficiency nanostructured devices. Here we show that nanostructuring is not
      necessary to achieve high efficiencies with this material: a simple planar
      heterojunction solar cell incorporating vapour-deposited perovskite as the
      absorbing layer can have solar-to-electrical power conversion efficiencies of
      over 15 per cent (as measured under simulated full sunlight). This demonstrates
      that perovskite absorbers can function at the highest efficiencies in simplified
      device architectures, without the need for complex nanostructures. 

PMID- 24025777
TI  - Symmetry breaking in nematic liquid crystals: analogy with cosmology and
      magnetism.
AB  - Universal behavior related to continuous symmetry breaking in nematic liquid
      crystals is studied using Brownian molecular dynamics. A three-dimensional
      lattice system of rod-like objects interacting via the Lebwohl-Lasher interaction
      is considered. We test the applicability of predictions originally derived in
      cosmology and magnetism. In the first part we focus on coarsening dynamics
      following the temperature driven isotropic-nematic phase transition for different
      quench rates. The behavior in the early coarsening regime supports predictions
      made originally by Kibble in cosmology. For fast enough quenches, symmetry
      breaking and causality give rise to a dense tangle of defects. When the degree of
      orientational ordering is large enough, well defined protodomains characterized
      by a single average domain length are formed. With time subcritical domains
      gradually vanish and supercritical domains grow with time, exhibiting a universal
      scaling law. In the second part of the paper we study the impact of random-field
      type disorder on a range of ordering in the (symmetry broken) nematic phase. We
      demonstrate that short-range order is observed even for a minute concentration of
      impurities, giving rise to disorder in line with the Imry-Ma theorem prediction
      only for the appropriate history of systems. 

PMID- 24025776
TI  - Biochemical and immunological mechanisms by which sickle cell trait protects
      against malaria.
AB  - Sickle cell trait (HbAS) is the best-characterized genetic polymorphism known to
      protect against falciparum malaria. Although the protective effect of HbAS
      against malaria is well known, the mechanism(s) of protection remain unclear. A
      number of biochemical and immune-mediated mechanisms have been proposed, and it
      is likely that multiple complex mechanisms are responsible for the observed
      protection. Increased evidence for an immune component of protection as well as
      novel mechanisms, such as enhanced tolerance to disease mediated by HO-1 and
      reduced parasitic growth due to translocation of host micro-RNA into the
      parasite, have recently been described. A better understanding of relevant
      mechanisms will provide valuable insight into the host-parasite relationship,
      including the role of the host immune system in protection against malaria. 

PMID- 24025778
TI  - In vivo optical coherence tomography of light-driven melanosome translocation in
      retinal pigment epithelium.
AB  - Optical coherence tomography (OCT) may revolutionize fundamental investigation
      and clinical management of age-related macular degeneration and other eye
      diseases. However, quantitative OCT interpretation is hampered due to uncertain
      sub-cellular correlates of reflectivity in the retinal pigment epithelium (RPE)
      and photoreceptor. The purpose of this study was twofold: 1) to test OCT
      correlates in the RPE, and 2) to demonstrate the feasibility of longitudinal OCT
      monitoring of sub-cellular RPE dynamics. A high resolution OCT was constructed to
      achieve dynamic imaging of frog eyes, in which light-driven translocation of RPE
      melanosomes occurred within the RPE cell body and apical processes. Comparative
      histological examination of dark- and light-adapted eyes indicated that the RPE
      melanin granule, i.e., melanosome, was a primary OCT correlate. In vivo OCT
      imaging of RPE melanosomes opens the opportunity for quantitative assessment of
      RPE abnormalities associated with disease, and enables longitudinal investigation
      of RPE kinetics correlated with visual function. 

PMID- 24025779
TI  - Small airway impairment in moderate to severe asthmatics without significant
      proximal airway obstruction.
AB  - Asthma is a disease characterized by inflammation which affects both proximal and
      distal airways. We evaluated the prevalence of small airway obstruction (SAO) in
      a group of clinically stable asthmatics with both normal forced expiratory volume
      in the first second (FEV1) and normal FEV1/forced vital capacity (FVC) and
      treated with an association of inhaled corticosteroids (ICSs) and long acting
      beta2-agonists (LABAs). Clinical evaluation included the measurement of dyspnea,
      asthma control test and drug compliance. The prevalence of SAO was estimated by
      spirometry and plethysmography and defined by the presence of one or more of the
      following criteria: functional residual capacity (FRC) > 120% predicted (pred),
      residual volume (RV) > pred + 1.64 residual standard deviation (RSD), RV/total
      lung capacity (TLC) > pred + 1.64 RSD, forced expiratory flow (FEF)25-75% < pred 
      1.64 RSD, FEF50% < pred - 1.64 RSD, slow vital capacity (SVC) - FVC > 10%. Among
      the 441 patients who were included, 222 had normal FEV1 and FEV1/FVC. At least
      one criteria of SAO was found in 115 (52%) mainly lung hyperinflation (39% based
      on high FRC, RV or RV/TLC) and more rarely distal airflow limitation (15% based
      on FEF25-75% or FEF50%) or expiratory trapping (10% based on increased SVC -
      FVC). In the patients with only SAO (no PAO), there was no relationship between
      SAO, asthma history and the scores of dyspnea, asthma control or drug compliance.
      These results suggest that in asthmatics with normal FEV1 and FEV1/FVC, treated
      with ICSs and LABAs, SAO is found in more than half of the patients indicating
      that the routinely used lung function tests can underestimate dysfunctions
      occurring in the small airways. 

PMID- 24025780
TI  - Directing reaction pathways by catalyst active-site selection using self
      assembled monolayers.
AB  - One key route for controlling reaction selectivity in heterogeneous catalysis is
      to prepare catalysts that exhibit only specific types of sites required for
      desired product formation. Here we show that alkanethiolate self-assembled
      monolayers with varying surface densities can be used to tune selectivity to
      desired hydrogenation and hydrodeoxygenation products during the reaction of
      furfural on supported palladium catalysts. Vibrational spectroscopic studies
      demonstrate that the selectivity improvement is achieved by controlling the
      availability of specific sites for the hydrogenation of furfural on supported
      palladium catalysts through the selection of an appropriate alkanethiolate.
      Increasing self-assembled monolayer density by controlling the steric bulk of the
      organic tail ligand restricts adsorption on terrace sites and dramatically
      increases selectivity to desired products furfuryl alcohol and methylfuran. This
      technique of active-site selection simultaneously serves both to enhance
      selectivity and provide insight into the reaction mechanism. 

PMID- 24025781
TI  - Imidacloprid, a neonicotinoid insecticide, induces insulin resistance.
AB  - Recently, scientific evidence supports a connection between environmental
      chemical exposures, which includes insecticides, and development of type 2
      diabetes. However, there is limited information about the link between influences
      of neonicotinoid insecticides and incidence of type 2 diabetes. Thus, the purpose
      of the study was to determine effects of imidacloprid, a neonicotinoid
      insecticide, on glucose metabolism. Three different cell models were used;
      adipocytes (3T3-L1), hepatocytes (HepG2), and myotubes (C2C12). These cells were
      treated with imidacloprid (0, 10, and 20 MUM) for 4-6 days followed by treatment
      with insulin for 15 min to determine responses. Insulin stimulated glucose uptake
      was reduced by imidacloprid in all three cell culture models. Treatment with
      imidacloprid reduced phosphorylation of protein kinase B (AKT), one of the major
      regulators of insulin signaling, without changing overall AKT expression.
      Subsequently, imidacloprid reduced phosphorylation of ribosomal S6 kinase (S6K),
      which is a downstream target of AKT and also a feed-back inhibitor of insulin
      signaling. These results suggest that imidacloprid could induce insulin
      resistance by affecting the insulin signaling cascade, particularly up-stream of
      AKT, in adipocytes, liver, and muscle. 

PMID- 24025783
TI  - c-Fos immunoreactivity of neural cells in intoxication due to high-dose
      methamphetamine.
AB  - Methamphetamine (METH) is a powerful and toxic psychostimulant that is abused
      worldwide. Although many studies of its toxic functions have been done on animals
      and humans, the mechanism is still poorly understood. In addition, the doses of
      METH examined have often been low. Here, we investigated the effects of
      intoxication due to administration of 20 mg/kg METH on neuronal activity. The
      mice showed hyperthermia and stereotyped behavior during 60 min after injection.
      We examined plasma stress hormone levels, which indicated that exposure to METH
      stimulated the hypothalamic-pituitary-adrenal (HPA) axis and caused release of
      stress hormones soon after injection. The maximum levels of adrenocorticotropic
      hormone and corticosterone occurred 10 and 60 min, respectively, after injection.
      We examined c-Fos protein in 16 different brain regions at 60 min post injection
      to identify potential brain regions subject to the stimulant effect. Nine
      regions, including the anterior hypothalamic area, medial preoptic area, lateral
      hypothalamic area, paraventricular thalamic nucleus, lateral anterior
      hypothalamic nucleus, lateral septum, striatum, nucleus accumbens, and amygdala,
      showed a significant increase in c-Fos expression, while the other seven regions
      did not. These results indicate that responsive neurons in the regions containing
      c-Fos immunoreactivity (Fos-IR) may undergo cellular reaction to high-dose METH
      administration. The present study provides support for a relationship among
      hyperthermia, the HPA axis and neuronal activities in limited brain regions on
      exposure to 20 mg/kg METH. 

PMID- 24025782
TI  - In vivo study on the effects of microcystin-LR on the apoptosis, proliferation
      and differentiation of rat testicular spermatogenic cells of male rats injected
      i.p. with toxins.
AB  - Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by
      cyanobacteria, has strong reproductive toxicity. The present study was designed
      to elucidate the mechanism of declines in sperm quality as a result of exposure
      to MC-LR by using spermatogenic cells as a model system. MC-LR was
      intraperitoneally administered to male rats daily at 0, 50 and 100 ug/kg body
      weight for one week. Results showed that changes occurred in the structural of
      testis, the tubular diameter and the relative weight of the testes was
      significantly decreased following treatment with 100 MUg/kg. Major differences in
      apoptosis and proliferation of testicular cells were observed at the100 MUg/kg MC
      LR. The gene expression levels of testis-specific histone 2B (TH2B) and
      transition protein 2 (TP2) were both significantly decreased. Meanwhile, the stem
      cell factor receptor (c-kit) was increased after exposure to 50 or 100 MUg/kg MC
      LR. This study demonstrated that MC-LR can alter the apoptosis, proliferation and
      differentiation of spermatogenic cells in vivo. 

PMID- 24025784
TI  - Suppressive effect of liver tumor-promoting activities in rats subjected to
      combined administration of phenobarbital and piperonyl butoxide.
AB  - Phenobarbital (PB) is a cytochrome P450 (CYP) 2B inducer, and piperonyl butoxide
      (PBO) is a CYP1A/2B inducer. These inducers have liver tumor-promoting effects in
      rats. In this study, we performed a rat two-stage liver carcinogenesis bioassay
      to examine the tumor-promoting effect of PB and PBO co-administration. Male rats
      received an intraperitoneal injection of N-diethylnitrosamine (DEN) for
      initiation. Two weeks after DEN administration, rats were given PB (60 or 120 ppm
      in drinking water), PBO (1,250 or 2,500 ppm in diet) or 60 ppm PB+1,250 ppm PBO
      for 6 weeks. One week after the PB/PBO treatment, all rats were subjected to a
      two-thirds partial hepatectomy. To evaluate the effect of the combined
      administration, we used two statistical additive models. In the isoadditive
      model, the average values of the area of GST-P positive foci in the PB+PBO group
      were significantly lower than those in the High PB or High PBO groups. In the
      heteroadditive model, the net values of Cyp1a1 mRNA level and microsomal reactive
      oxygen species (ROS) production in the PB+PBO group were significantly lower than
      the sum of those in the Low PB or Low PBO groups. On the contrary, there was no
      interactive effect in the PCNA-positive hepatocyte ratio, mRNA levels of
      Cyp2b1/2, Gstm3, Gpx2 and Nqo1, and the level of thiobarbituric acid-reactive
      substances in the PB+PBO group. These results suggest that PB and PBO co
      administration causes suppressive effects in liver tumor-promoting activity in
      rats resulting from inhibited microsomal ROS production because of suppression of
      CYP1A induction. 

PMID- 24025785
TI  - Increase in accumulation of polychlorinated biphenyls in offspring mouse brain
      via maternal coexposure to methylmercury and polychlorinated biphenyls.
AB  - Methylmercury (MeHg) and polychlorinated biphenyls (PCBs) are environmentally
      persistent neurodevelopmental toxicants. In Japan, the most common source of
      human exposure is the consumption of contaminated fish and seafood. We
      investigated the accumulation of MeHg and PCBs in the brains of dams and
      offspring mice maternally exposed to MeHg and/or PCBs. Pregnant mice (C57BL/6Cr)
      were assigned to one of four exposure groups: control, MeHg alone (MeHg in diet
      at 5 mg/kg as Hg), PCB alone (Aroclor1254 by gavage at the dose of 18 mg/kg body
      weight/3 days) and MeHg+PCB. Levels of MeHg and PCBs were measured in the whole
      brains of dams and offspring mice on postnatal day 21 (PND21) and at 9 weeks of
      age. Total mercury, MeHg and PCB congener concentrations were determined by
      CVAAS, GC-ECD and HRGC/HRMS, respectively. For the mercury concentrations, there
      were no significant differences between MeHg alone and MeHg+PCB except for pups
      at 9 weeks. The maternal PCB levels were not significantly different between
      MeHg+PCB and PCB alone. In pup brain on PND21, MeHg+PCB resulted in a
      significantly higher PCB level than PCB alone. Although the levels of lightly
      chlorinated (= 4CBs) homologues were lower for MeHg+PCB than for PCB alone, those
      of highly chlorinated (>= 5CBs) homologues were significantly higher on PND21 for
      MeHg+PCB. The PCB composition in dams and pups shifted to higher chlorinated
      homologues compared with the composition of administered Aroclor1254. For these
      reasons, further detailed studies are necessary to clarify the interactional
      effects of PCB metabolism after coexposure to MeHg and PCBs. 

PMID- 24025786
TI  - Sodium dodecyl sulfate and sodium dodecyl benzenesulfonate are ligands for
      peroxisome proliferator-activated receptor gamma.
AB  - Sodium dodecyl sulfate (SDS) and sodium dodecyl benzenesulfonate (SDBS) are
      widely used anionic surfactants in household, industrial, and institutional
      cleaners. Although there are many reports of their toxic effects, few studies
      have focused on the pharmacological properties of these surfactants. Peroxisome
      proliferator-activated receptor (PPAR) gamma is a transcriptional factor
      belonging to the nuclear receptor superfamily. The ligands of PPARgamma regulate
      its transcriptional activity and modulate many biological functions, including
      adipocyte differentiation and lipid metabolism. In this study, we investigated
      the ligand activities of SDS and SDBS for nuclear receptors using time-resolved
      fluorescence resonance energy transfer-based coactivator recruitment assays. SDS
      and SDBS showed selective ligand activities for PPARgamma and these ligand
      activities were eliminated by a PPARgamma antagonist. SDS and SDBS also promoted
      adipocyte differentiation accompanied by upregulation of adipocyte-specific gene
      expression in 3T3-L1 preadipocytes. These findings reveal novel actions of
      anionic alkyl surfactants as PPARgamma ligands. 

PMID- 24025787
TI  - Changes in the levels of low molecular weight metabolites in the mouse cerebellum
      following treatment with methylmercury.
AB  - Metabolomic analysis was performed using the cerebellum of methylmercury-treated
      mice to elucidate the molecular mechanisms underlying methylmercury-induced
      cerebellar dysfunction. Methylmercury administration led to significant increases
      in the levels of 11 low molecular weight metabolites and significant reductions
      in the levels of 29 others, including several metabolites produced by amino acid
      and purine metabolism. Non-significant decreases in metabolites involved in the
      TCA cycle and in glutathione metabolism were also observed. 

PMID- 24025788
TI  - Disruption of elastic lamellae in the aorta by D-penicillamine and its effect on
      vaso-regulation in rats.
AB  - We assessed the effects of D-penicillamine (D-PA) on cross-linkages in elastin
      and vaso-regulatory function in rats. After administration of D-PA at a dose of
      100 mg/kg/day for 7 weeks to adult and young rats, the thoracic aortas were
      isolated. The elastic lamellae in the aorta were disrupted histopathologically in
      all the treated groups. The content of cross-linkages in elastin, i.e. desmosine
      and isodesmosine, which gives elasticity to the aortic wall, was significantly
      reduced in the D-PA treated groups versus the control groups. On the other hand,
      the content of pyridinoline as a marker of insoluble collagen was significantly
      reduced in the D-PA treated groups, even though the total collagen content was
      not changed. In addition, after 7 weeks of treatment with D-PA, the change
      between systolic blood pressure before and after sympathetic stimulation (Delta
      SBP) by L-epinephrine was about 2.5-fold larger than that in the control group.
      Similar results were obtained using angiotensin II or ouabain instead of L
      epinephrine. These findings demonstrated that D-PA disrupted elastic lamellae of
      the rat aorta by reduction of the cross-linkages in elastin and collagen, which
      caused dysfunction of vaso-regulation. Also, they suggested the possibility that
      long-term treatment with D-PA in patients could cause a decrease in vaso
      regulatory function and could increase the risk of cardiovascular events. 

PMID- 24025789
TI  - Disruption of elastic lamellae in aorta and dysfunction of vaso-regulation by
      rofecoxib in rats.
AB  - We assessed the effects of rofecoxib on cross-linkage formation in elastin and
      vaso-regulatory function in rats. After administration of rofecoxib at a dose of
      10 mg/kg for 7 weeks to young rats and for 7 and 10 weeks to adult rats, thoracic
      aortas were isolated. The elastic lamellae in the aortas were disrupted
      histopathologically in all the treated groups. However, the content of cross
      linkages in elastin, i.e. desmosine and isodesmosine, which give elasticity to
      the aortic wall, was not significantly different between the rofecoxib treated
      and control groups. On the other hand, although the baseline blood pressure was
      not changed during the treatment period in both young and adult rats, after
      several weeks of treatment with rofecoxib the change between systolic blood
      pressure before and after sympathetic stimulation by L-epinephrine was 2 to 3
      fold larger than that in the control group. Similar results were obtained using
      angiotensin II instead of L-epinephrine. The exposure to rofecoxib (area under
      the plasma concentration-time curve) of rats after single administration was a
      few times higher than that of humans in clinical use. These findings indicate
      that rofecoxib did not directly inhibit formation of cross-linkages in elastin of
      the aorta in rats. However, the treatment with rofecoxib for several weeks
      disrupted elastic lamellae and caused depression of vaso-regulatory function in
      rats, which could bring on an increased risk of cardiovascular events in human. 

PMID- 24025790
TI  - First-principles Wannier function analysis of the electronic structure of PdTe:
      weaker magnetism and superconductivity.
AB  - We report a first-principles Wannier function study of the electronic structure
      of PdTe. Its electronic structure is found to be a broad three-dimensional Fermi
      surface with highly reduced correlation effects. In addition, the higher filling
      of the Pd d-shell, its stronger covalency resulting from the closer energy of the
      Pd d and Te p shells, and the larger crystal field effects of the Pd ion due to
      its near octahedral coordination, all serve to weaken significantly electronic
      correlations in the particle-hole (spin, charge, and orbital) channel. In
      comparison to the Fe chalcogenides, e.g. FeSe, we highlight the essential
      features (quasi-two-dimensionality, proximity to half-filling, weaker covalency,
      and higher orbital degeneracy) of Fe-based high-temperature superconductors. 

PMID- 24025791
TI  - RNAi screening identifies GSK3beta as a regulator of DRP1 and the neuroprotection
      of lithium chloride against elevated pressure involved in downregulation of DRP1.
AB  - Elevated intraocular pressure (IOP) is considered as the major risk factor for
      the loss of retinal ganglion cells (RGCs) and their axons in glaucoma. Emerging
      evidence suggests elevated IOP can induce Drp1 upregulation and mitochondrial
      fission, which is involved in cell death. However, the underlying mechanism for
      these effects remains unknown. The present study used RNAi screening to
      investigate the effects of 24 kinases associated with mitochondrial activities on
      DRP1 expression under hydrostatic pressure. We identified, for the first time,
      that glycogen synthase kinase 3 beta (GSK3beta) knockdown suppressed the
      upregulation of DRP1 induced by elevated pressure. Use of the pharmacological
      inhibitor of GSK3beta inhibitor, lithium chloride (LiCl), confirmed this result.
      Furthermore, we demonstrated that one of the mechanisms of lithium chloride
      neuroprotection might be via inhibition of mitochondrial fission through
      downregulation of Drp1. 

PMID- 24025792
TI  - Electrochemical biosensors on platforms of graphene.
AB  - In recent years, graphene, the two-dimensional closely packed honeycomb carbon
      lattice, has been attracting much attention in the field of electrochemistry due
      to its intrinsic properties and merits. Efforts to create novel graphene based
      electrochemical biosensors have led to the establishment of effective strategies
      for diverse bioassays, from simple molecules to complex biotargets. In this
      Feature Article, we provide an overview of electrochemical biosensing with
      graphene related materials, and discuss the role of graphene in different sensing
      protocols. 

PMID- 24025794
TI  - Delayed recovery of leg fatigue symptoms following a maximal exercise session in
      people with multiple sclerosis.
AB  - BACKGROUND: Fatigue is a chronic symptom for people with multiple sclerosis
      (PwMS). OBJECTIVE: Symptoms of fatigue were investigated during and following a
      single exercise session. METHODS: In all, 58 PwMS and 15 healthy, low-active
      controls performed a cycle ergometer incremental exercise test to voluntary
      exhaustion. Physiological intensity (expired air and heart rate), perceived
      breathlessness, and leg fatigue (Rating of Perceived Exertion [RPE] CR-10 Scale)
      were measured during and for 10 minutes following exercise. MEASURES: of baseline
      disability (Barthel Index), activity (Physical Activity Scale for the Elderly),
      vitality (Subjective Vitality Scale), and general fatigue (Fatigue Severity Scale
      [FSS]) were recorded. RESULTS: PwMS had reduced exercise capacity (P = .00 to
      .01), but sensations of breathlessness and leg fatigue were the same at voluntary
      exercise termination in both groups (P = .09). PwMS with fatigue (FSS >= 4)
      exhibited reduced exercise capacity (P = .03 to .05) but reached the same
      physiological intensity, breathlessness, and leg fatigue symptoms at test
      termination as nonfatigued peers (P = .16 to .59). During recovery, there was no
      difference in observed means between groups, except for leg RPE, which was higher
      in the MS group (P = .047) and higher at 3 and 5 minutes after exercise in the
      fatigued MS group (P = .02). Physiological markers and breathlessness recovered
      at the same rate in both groups (P = .33 to .67). CONCLUSION: Monitoring leg
      fatigue symptoms during and through recovery from physical activities may help
      guide participation in physical activities for PwMS, particularly in people
      managing high levels of fatigue.

PMID- 24025793
TI  - Substantial loss of conserved and gain of novel MicroRNA families in flatworms.
AB  - Recent studies on microRNA (miRNA) evolution focused mainly on the comparison of
      miRNA complements between animal clades. However, evolution of miRNAs within such
      groups is poorly explored despite the availability of comparable data that in
      some cases lack only a few key taxa. For flatworms (Platyhelminthes), miRNA
      complements are available for some free-living flatworms and all major parasitic
      lineages, except for the Monogenea. We present the miRNA complement of the
      monogenean flatworm Gyrodactylus salaris that facilitates a comprehensive
      analysis of miRNA evolution in Platyhelminthes. Using the newly designed
      bioinformatics pipeline miRCandRef, the miRNA complement was disentangled from
      next-generation sequencing of small RNAs and genomic DNA without a priori genome
      assembly. It consists of 39 miRNA hairpin loci of conserved miRNA families, and
      22 novel miRNAs. A comparison with the miRNA complements of Schmidtea
      mediterranea (Turbellaria), Schistosoma japonicum (Trematoda), and Echinococcus
      granulosus (Cestoda) reveals a substantial loss of conserved bilaterian,
      protostomian, and lophotrochozoan miRNAs. Eight of the 46 expected conserved
      miRNAs were lost in all flatworms, 16 in Neodermata and 24 conserved miRNAs could
      not be detected in the cestode and the trematode. Such a gradual loss of miRNAs
      has not been reported before for other animal phyla. Currently, little is known
      about miRNAs in Platyhelminthes, and for the majority of the lost miRNAs there is
      no prediction of function. As suggested earlier they might be related to
      morphological simplifications. The presence and absence of 153 conserved miRNAs
      was compared for platyhelminths and 32 other metazoan taxa. Phylogenetic analyses
      support the monophyly of Platyhelminthes (Turbellaria + Neodermata [Monogenea
      {Trematoda + Cestoda}]). 

PMID- 24025796
TI  - United States of America: health system review.
AB  - This analysis of the United States health system reviews the developments in
      organization and governance, health financing, health-care provision, health
      reforms and health system performance. The US health system has both considerable
      strengths and notable weaknesses. It has a large and well-trained health
      workforce, a wide range of high-quality medical specialists as well as secondary
      and tertiary institutions, a robust health sector research program and, for
      selected services, among the best medical outcomes in the world. But it also
      suffers from incomplete coverage of its citizenry, health expenditure levels per
      person far exceeding all other countries, poor measures on many objective and
      subjective measures of quality and outcomes, an unequal distribution of resources
      and outcomes across the country and among different population groups, and
      lagging efforts to introduce health information technology. It is difficult to
      determine the extent to which deficiencies are health-system related, though it
      seems that at least some of the problems are a result of poor access to care.
      Because of the adoption of the Affordable Care Act in 2010, the United States is
      facing a period of enormous potential change. Improving coverage is a central
      aim, envisaged through subsidies for the uninsured to purchase private insurance,
      expanded eligibility for Medicaid (in some states) and greater protection for
      insured persons. Furthermore, primary care and public health receive increased
      funding, and quality and expenditures are addressed through a range of measures.
      Whether the ACA will indeed be effective in addressing the challenges identified
      above can only be determined over time. 

PMID- 24025795
TI  - In vitro suppression of immune responses using monocyte-derived tolerogenic
      dendritic cells from patients with primary Sjogren's syndrome.
AB  - INTRODUCTION: Therapeutic vaccination with antigen-specific tolerogenic dendritic
      cells (tolDC) might become a future option of individualized therapy for patients
      with autoimmune diseases. In this study, we tested the possibility of generating
      monocyte-derived tolDC from patients with primary Sjogren's syndrome (pSS). We
      analyzed phenotype, cytokine production and ability to suppress Ro/La-specific
      immune responses. METHODS: Monocyte-derived tolDC from patients with pSS were
      generated in the presence of dexamethasone, vitamin D3 and lipopolysaccharide
      (DexVD3 DC). The phenotype was analyzed by flow cytometry and the cytokine
      profile was investigated using a 25-plex Luminex assay and ELISA. The capacity to
      both stimulate Ro/La-specific T cells and suppress this response was evaluated by
      autologous mixed lymphocyte reaction (MLR). RESULTS: DC generated from patients
      with pSS had a similar phenotype and cytokine profile to those from healthy
      controls. DexVD3 DC from pSS patients induced little antigen-specific T cell
      proliferation, but DexVD3 DC-primed lymphocytes successfully suppressed Ro/La
      specific T cell responses. CONCLUSIONS: DexVD3 DC presenting Ro/La antigens might
      be a promising new therapeutic option for patients with pSS.

PMID- 24025797
TI  - The upper brachial plexus defect model in rhesus monkeys: a cadaveric feasibility
      study.
AB  - To establish a model for nerve grafts and determine the anatomic characteristics
      of the brachial plexus in rhesus monkeys. Ten specimens of the brachial plexus
      were obtained from five rhesus monkey cadavers. Anatomic dissection of the
      brachial plexus was systemically performed. The length of each root, trunk, and
      each division was measured using a Vernier caliper proximodistally. The anatomic
      distributions of the suprascapular, axillary, and musculocutaneous nerve were
      documented. The brachial plexus of rhesus monkeys included the spinal nerves or
      roots of C5, C6, C7, C8, and T1 (80%, 8/10), with a small contribution from the
      C4 root (20%, 2/10) occasionally. The upper trunk was not measurable because of
      their irregular structures. The lower trunk had a mean length of 1.62 (range,
      0.96-2.1 mm) and a mean diameter of 2.29 (range, 1.9-2.94 mm). For the upper
      trunk, the C5 and C6 roots either divided into two very short divisions or sent
      out very long divisions before they joined together. For the middle trunk, the C7
      root had a straight course after leaving the foramen and blended imperceptibly
      into the middle trunk before dividing into the anterior and posterior divisions.
      The lower trunk was noted in almost all the specimens (80%, 8/10), which was
      formed by C8 and T1. The brachial plexus in rhesus monkeys varies from that of
      humans, and defects can be made at the level of C5 and C6 roots and the C7 root
      should also be cut off and ligated. 

PMID- 24025798
TI  - Semantic processing and response inhibition.
AB  - The present study examined functional MRI (fMRI) BOLD signal changes in response
      to object categorization during response selection and inhibition. Young adults
      (N=16) completed a Go/NoGo task with varying object categorization requirements
      while fMRI data were recorded. Response inhibition elicited increased signal
      change in various brain regions, including medial frontal areas, compared with
      response selection. BOLD signal in an area within the right angular gyrus was
      increased when higher-order categorization was mandated. In addition, signal
      change during response inhibition varied with categorization requirements in the
      left inferior temporal gyrus (lIT). lIT-mediated response inhibition when
      inhibiting the response only required lower-order categorization, but lIT
      mediated both response selection and inhibition when selecting and inhibiting the
      response required higher-order categorization. The findings characterized
      mechanisms mediating response inhibition associated with semantic object
      categorization in the 'what' visual object memory system. 

PMID- 24025799
TI  - Differential effects of antihypertensive treatments on apoptosis, oxidative
      stress, and expression of angiotensin receptors in the cerebral cortex from the
      onset of prehypertension and hypertension in stroke-prone spontaneous
      hypertensive rats.
AB  - To investigate the effects of losartan and amlodipine on cell apoptosis in the
      cerebral cortex of stroke-prone spontaneously hypertensive rats (SHRSP) from the
      onset of prehypertension or hypertension. SHRSP were randomly divided into five
      experimental groups that were administered losartan, amlodipine (n=8 in each
      group; 4 weeks old or 10 weeks old), or vehicle, respectively. Wistar-Kyoto rats
      were used as control animals. Systolic blood pressure was measured using the tail
      cuff method every 2 weeks. At 20 weeks of age, apoptosis was analyzed by TdT
      mediated dUTP-biotin nick end labeling, and the level of angiotensin II was
      measured by radioimmunoassay. Protein expressions of gp91(phox), superoxide
      dismutase, and angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors in the
      cerebral cortex were detected by western blot. Losartan and amlodipine
      effectively delayed the progression of systolic blood pressure elevation,
      especially from the onset of prehypertension, and they had no obvious effects on
      the level of angiotensin II. In addition, treatment with losartan or amlodipine
      significantly decreased cell apoptosis, downregulated the protein expression of
      gp91(phox), and upregulated the protein expression of superoxide dismutase. The
      protein expressions of AT1R and AT2R were decreased by the administration of both
      drugs. No difference was found in the expression of AT1R among the drug treatment
      groups, whereas the expression of AT2R was increased in rats with increased blood
      pressure. Amlodipine, especially from the onset of prehypertension, was more
      effective than losartan in reducing apoptosis in the cerebral cortex in SHRSP.
      This may be related to the antioxidative stress properties of amlodipine.

PMID- 24025800
TI  - Time course of brain activation elicited by basic emotions.
AB  - Whereas facial emotion recognition protocols have shown that each discrete
      emotion has a specific time course of brain activation, there is no
      electrophysiological evidence to support these findings for emotional induction
      by complex pictures. Our objective was to specify the differences between the
      time courses of brain activation elicited by feelings of happiness and, with
      unpleasant pictures, by feelings of disgust and sadness. We compared event
      related potentials (ERPs) elicited by the watching of high-arousing pictures from
      the International Affective Picture System, selected to induce specific emotions.
      In addition to a classical arousal effect on late positive components, we found
      specific ERP patterns for each emotion in early temporal windows (<200 ms).
      Disgust was the first emotion to be associated with different brain processing
      after 140 ms, whereas happiness and sadness differed in ERPs elicited at the
      frontal and central sites after 160 ms. Our findings highlight the limits of the
      classical averaging of ERPs elicited by different emotions inside the same
      valence and suggest that each emotion could elicit a specific temporal pattern of
      brain activation, similar to those observed with emotional face recognition. 

PMID- 24025801
TI  - Subfunctionalization of sigma factors during the evolution of land plants based
      on mutant analysis of liverwort (Marchantia polymorpha L.) MpSIG1.
AB  - Sigma factor is a subunit of plastid-encoded RNA polymerase that regulates the
      transcription of plastid-encoded genes by recognizing a set of promoters. Sigma
      factors have increased in copy number and have diversified during the evolution
      of land plants, but details of this process remain unknown. Liverworts represent
      the basal group of embryophytes and are expected to retain the ancestral features
      of land plants. In liverwort (Marchantia polymorpha L.), we isolated and
      characterized a T-DNA-tagged mutant (Mpsig1) of sigma factor 1 (MpSIG1). The
      mutant did not show any visible phenotypes, implying that MpSIG1 function is
      redundant with that of other sigma factors. However, quantitative reverse
      transcription polymerase chain reaction and RNA gel blot analysis revealed that
      genes related to photosynthesis were downregulated, resulting in the minor
      reduction of some protein complexes. The transcript levels of genes clustered in
      the petL, psaA, psbB, psbK, and psbE operons of liverwort were lower than those
      in the wild type, a result similar to that in the SIG1 defective mutant in rice
      (Oryza sativa). Overexpression analysis revealed primitive functional divergence
      between the SIG1 and SIG2 proteins in bryophytes, whereas these proteins still
      retain functional redundancy. We also discovered that the predominant sigma
      factor for ndhF mRNA expression has been diversified in liverwort, Arabidopsis
      (Arabidopsis thaliana), and rice. Our study shows the ancestral function of SIG1
      and the process of functional partitioning (subfunctionalization) of sigma
      factors during the evolution of land plants. 

PMID- 24025803
TI  - It is time to update US biomedical funding.

PMID- 24025815
TI  - Grey wolves left out in the cold.

PMID- 24025816
TI  - Physicists net fractal butterfly.

PMID- 24025802
TI  - Network-based approaches in drug discovery and early development.
AB  - Identification of novel targets is a critical first step in the drug discovery
      and development process. Most diseases such as cancer, metabolic disorders, and
      neurological disorders are complex, and their pathogenesis involves multiple
      genetic and environmental factors. Finding a viable drug target-drug combination
      with high potential for yielding clinical success within the efficacy-toxicity
      spectrum is extremely challenging. Many examples are now available in which
      network-based approaches show potential for the identification of novel targets
      and for the repositioning of established targets. The objective of this article
      is to highlight network approaches for identifying novel targets with greater
      chances of gaining approved drugs with maximal efficacy and minimal side effects.
      Further enhancement of these approaches may emerge from effectively integrating
      computational systems biology with pharmacodynamic systems analysis. Coupling
      genomics, proteomics, and metabolomics databases with systems pharmacology
      modeling may aid in the development of disease-specific networks that can be
      further used to build confidence in target identification. 

PMID- 24025817
TI  - Hackles rise over privatization plan.

PMID- 24025818
TI  - Secrets of fracking fluids pave way for cleaner recipe.

PMID- 24025820
TI  - Ultimate upgrade for US synchrotron.

PMID- 24025819
TI  - More cuts loom for US science.

PMID- 24025822
TI  - Taxonomy: The spy who loved frogs.

PMID- 24025823
TI  - Physics: Quantum quest.

PMID- 24025828
TI  - Biology: A forgotten history of sex research.

PMID- 24025830
TI  - Politics: Turkey's scientists can't ignore politics.

PMID- 24025829
TI  - Genomics: HeLa genome versus donor's genome.

PMID- 24025831
TI  - Data sharing: Don't compromise on informed consent.

PMID- 24025832
TI  - Neuroscience: transcranial devices are not playthings.

PMID- 24025833
TI  - Anthony James Pawson (1952-2013).

PMID- 24025834
TI  - Social science: The mathematics of murder.

PMID- 24025835
TI  - Materials science: Boosting X-ray emission.

PMID- 24025837
TI  - Astrochemistry: Extracts of meteorite.

PMID- 24025838
TI  - Social reward requires coordinated activity of nucleus accumbens oxytocin and
      serotonin.
AB  - Social behaviours in species as diverse as honey bees and humans promote group
      survival but often come at some cost to the individual. Although reinforcement of
      adaptive social interactions is ostensibly required for the evolutionary
      persistence of these behaviours, the neural mechanisms by which social reward is
      encoded by the brain are largely unknown. Here we demonstrate that in mice
      oxytocin acts as a social reinforcement signal within the nucleus accumbens core,
      where it elicits a presynaptically expressed long-term depression of excitatory
      synaptic transmission in medium spiny neurons. Although the nucleus accumbens
      receives oxytocin-receptor-containing inputs from several brain regions, genetic
      deletion of these receptors specifically from dorsal raphe nucleus, which
      provides serotonergic (5-hydroxytryptamine; 5-HT) innervation to the nucleus
      accumbens, abolishes the reinforcing properties of social interaction.
      Furthermore, oxytocin-induced synaptic plasticity requires activation of nucleus
      accumbens 5-HT1B receptors, the blockade of which prevents social reward. These
      results demonstrate that the rewarding properties of social interaction in mice
      require the coordinated activity of oxytocin and 5-HT in the nucleus accumbens, a
      mechanistic insight with implications for understanding the pathogenesis of
      social dysfunction in neuropsychiatric disorders such as autism. 

PMID- 24025839
TI  - Stereoinversion of tertiary alcohols to tertiary-alkyl isonitriles and amines.
AB  - The SN2 reaction (bimolecular nucleophilic substitution) is a well-known chemical
      transformation that can be used to join two smaller molecules together into a
      larger molecule or to exchange one functional group for another. The SN2 reaction
      proceeds in a very predictable manner: substitution occurs with inversion of
      stereochemistry, resulting from the 'backside attack' of the electrophilic carbon
      by the nucleophile. A significant limitation of the SN2 reaction is its
      intolerance for tertiary carbon atoms: whereas primary and secondary alcohols are
      viable precursor substrates, tertiary alcohols and their derivatives usually
      either fail to react or produce stereochemical mixtures of products. Here we
      report the stereochemical inversion of chiral tertiary alcohols with a
      nitrogenous nucleophile facilitated by a Lewis-acid-catalysed solvolysis. The
      method is chemoselective against secondary and primary alcohols, thereby
      complementing the selectivity of the SN2 reaction. Furthermore, this method for
      carbon-nitrogen bond formation mimics a putative biosynthetic step in the
      synthesis of marine terpenoids and enables their preparation from the
      corresponding terrestrial terpenes. We expect that the general attributes of the
      methodology will allow chiral tertiary alcohols to be considered viable
      substrates for stereoinversion reactions. 

PMID- 24025840
TI  - Retardation of arsenic transport through a Pleistocene aquifer.
AB  - Groundwater drawn daily from shallow alluvial sands by millions of wells over
      large areas of south and southeast Asia exposes an estimated population of over a
      hundred million people to toxic levels of arsenic. Holocene aquifers are the
      source of widespread arsenic poisoning across the region. In contrast,
      Pleistocene sands deposited in this region more than 12,000 years ago mostly do
      not host groundwater with high levels of arsenic. Pleistocene aquifers are
      increasingly used as a safe source of drinking water and it is therefore
      important to understand under what conditions low levels of arsenic can be
      maintained. Here we reconstruct the initial phase of contamination of a
      Pleistocene aquifer near Hanoi, Vietnam. We demonstrate that changes in
      groundwater flow conditions and the redox state of the aquifer sands induced by
      groundwater pumping caused the lateral intrusion of arsenic contamination more
      than 120 metres from a Holocene aquifer into a previously uncontaminated
      Pleistocene aquifer. We also find that arsenic adsorbs onto the aquifer sands and
      that there is a 16-20-fold retardation in the extent of the contamination
      relative to the reconstructed lateral movement of groundwater over the same
      period. Our findings suggest that arsenic contamination of Pleistocene aquifers
      in south and southeast Asia as a consequence of increasing levels of groundwater
      pumping may have been delayed by the retardation of arsenic transport. 

PMID- 24025842
TI  - Next-generation sequencing: The genome jigsaw.

PMID- 24025841
TI  - A type III effector antagonizes death receptor signalling during bacterial gut
      infection.
AB  - Successful infection by enteric bacterial pathogens depends on the ability of the
      bacteria to colonize the gut, replicate in host tissues and disseminate to other
      hosts. Pathogens such as Salmonella, Shigella and enteropathogenic and
      enterohaemorrhagic (EPEC and EHEC, respectively) Escherichia coli use a type III
      secretion system (T3SS) to deliver virulence effector proteins into host cells
      during infection that promote colonization and interfere with antimicrobial host
      responses. Here we report that the T3SS effector NleB1 from EPEC binds to host
      cell death-domain-containing proteins and thereby inhibits death receptor
      signalling. Protein interaction studies identified FADD, TRADD and RIPK1 as
      binding partners of NleB1. NleB1 expressed ectopically or injected by the
      bacterial T3SS prevented Fas ligand or TNF-induced formation of the canonical
      death-inducing signalling complex (DISC) and proteolytic activation of caspase-8,
      an essential step in death-receptor-induced apoptosis. This inhibition depended
      on the N-acetylglucosamine transferase activity of NleB1, which specifically
      modified Arg 117 in the death domain of FADD. The importance of the death
      receptor apoptotic pathway to host defence was demonstrated using mice deficient
      in the FAS signalling pathway, which showed delayed clearance of the EPEC-like
      mouse pathogen Citrobacter rodentium and reversion to virulence of an nleB
      mutant. The activity of NleB suggests that EPEC and other attaching and effacing
      pathogens antagonize death-receptor-induced apoptosis of infected cells, thereby
      blocking a major antimicrobial host response. 

PMID- 24025844
TI  - Nosema ceranae has been present in Brazil for more than three decades infecting
      Africanized honey bees.
AB  - Until the mid-1990s, the only microsporidium known to infect bees of the genus
      Apis was Nosema apis. A second species, Nosema ceranae, was first identified in
      1996 from Asian honey bees; it is postulated that this parasite was transmitted
      from the Asian honey bee, Apis cerana, to the European honey bee, Apis mellifera.
      Currently, N. ceranae is found on all continents and has often been associated
      with honey bee colony collapse and other reports of high bee losses. Samples of
      Africanized drones collected in 1979, preserved in alcohol, were analyzed by
      light microscopy to count spores and were subjected to DNA extraction, after
      which duplex PCR was conducted. All molecular analyses (triplicate) indicated
      that the drones were infected with both N. ceranae and N. apis. PCR products were
      sequenced and matched to sequences reported in the GenBank (Acc. Nos. JQ639316.1
      and JQ639301.1). The venation pattern of the wings of these males was compared to
      those of the current population living in the same area and with the pattern of
      drones collected in 1968 from Ribeirao Preto, SP, Brazil, from a location close
      to where African swarms first escaped in 1956. The morphometric results indicated
      that the population collected in 1979 was significantly different from the
      current living population, confirming its antiquity. Considering that the use of
      molecular tools for identifying Nosema species is relatively recent, it is
      possible that previous reports of infections (which used only light microscopy,
      without ultrastructural analysis) wrongly identified N. ceranae as N. apis.
      Although we can conclude that N. ceranae has been affecting Africanized honeybees
      in Brazil for at least 34 years, the impact of this pathogen remains unclear.

PMID- 24025845
TI  - Taking stock of Myanmar's progress toward the health-related Millennium
      Development Goals: current roadblocks, paths ahead.
AB  - Myanmar is a developing country with considerable humanitarian needs, rendering
      its pursuit of the Millennium Development Goals (MDGs) an especially high
      priority. Yet progress to date remains under-examined on key fronts. Particularly
      within the three health-related MDGs (MDGs 4, 5, and 6), the limited data
      reported point to patchy levels of achievement. This study was undertaken to
      provide an overview and assessment of Myanmar's progress toward the health
      related MDGs, along with possible solutions for accelerating health-related
      development into 2015 and beyond. The review highlights off-track progress in the
      spheres of maternal and child health (MDGs 4 and 5). It also shows Myanmar's
      achievements toward MDG 6 targets--in the areas of HIV/AIDS, malaria, and
      tuberculosis. Such achievements are especially notable in that Myanmar has been
      receiving the lowest level of official development assistance among all of the
      least developed countries in Asia. However, to make similar progress in MDGs 4
      and 5, Myanmar needs increased investment and commitment in health. Toward moving
      forward with the post-2015 development agenda, Myanmar's government also needs to
      take the lead in calling for attention from the World Health Organization and its
      global development partners to address the stagnation in health-related
      development progress within the country. In particular, Myanmar's government
      should invest greater efforts into health system strengthening to pave the road
      to universal health coverage.

PMID- 24025846
TI  - The triple test.

PMID- 24025847
TI  - The long gestation of the modern home pregnancy test.

PMID- 24025848
TI  - Evaluation of normalization strategies used in real-time quantitative PCR
      experiments in HepaRG cell line studies.
AB  - BACKGROUND: The HepaRG cell line is widely used as an alternative for primary
      human hepatocytes for numerous applications, including drug screening, and is
      progressively gaining importance as a human-relevant cell source. Consequently,
      increasing numbers of experiments are being performed with this cell line,
      including real-time quantitative PCR (RT-qPCR) experiments for gene expression
      studies. CONTENT: When RT-qPCR experiments are performed, results are reliable
      only when attention is paid to several critical aspects, including a proper
      normalization strategy. Therefore, in 2011 we determined the most optimal
      reference genes for gene expression studies in the HepaRG cell system, according
      to the MIQE (Minimum Information for Publication of Quantitative Real-Time PCR
      Experiments) guidelines. This study additionally provided clear evidence that the
      use of a single reference gene [glyceraldehyde-3-phosphate dehydrogenase (GAPDH),
      ribosomal protein S18 (RPS18), or actin, beta (ACTB)] was insufficient for
      normalization in HepaRG cells. Our screening of relevant studies published after
      our study suggested that the findings of our study were completely ignored.
      SUMMARY: In none of the 24 reviewed studies was a proper normalization method
      used. Only 1 reference gene was included for normalization in 21 out of the 24
      reported studies we screened, with RPS18 and GAPDH used most frequently, followed
      by hypoxanthine phosphoribosyltransferase 1 (HPRT1), glutathione synthetase (GSS)
      (hGus), beta-2 microglobin (B2M), and acidic ribosomal phosphoprotein P0 (36B4).
      For 2 studies the use of multiple reference genes (2 and 3) was reported, but
      these had not been prevalidated for expression stability in HepaRG cells. In 1
      study, there was no evidence that any reference gene had been used. Current RT
      qPCR gene expression studies in HepaRG cells are being performed without adequate
      consideration or evaluation of reference genes. Such studies can yield erroneous
      and biologically irrelevant results.

PMID- 24025849
TI  - Morphogenesis of defects and tactoids during isotropic-nematic phase transition
      in self-assembled lyotropic chromonic liquid crystals.
AB  - We explore the structure of nuclei and topological defects in the first-order
      phase transition between the nematic (N) and isotropic (I) phases in lyotropic
      chromonic liquid crystals (LCLCs). The LCLCs are formed by self-assembled
      molecular aggregates of various lengths and show a broad biphasic region. The
      defects emerge as a result of two mechanisms: (1) surface-anisotropy that endows
      each N nucleus ('tactoid') with topological defects thanks to preferential
      (tangential) orientation of the director at the closed I-N interface, and (2)
      Kibble mechanism with defects forming when differently oriented N tactoids merge
      with each other. Different scenarios of phase transition involve positive (N-in
      I) and negative (I-in-N) tactoids with nontrivial topology of the director field
      and also multiply connected tactoid-in-tactoid configurations. The closed I-N
      interface limiting a tactoid shows a certain number of cusps; the lips of the
      interface on the opposite sides of the cusp make an angle different from pi. The
      N side of each cusp contains a point defect-boojum. The number of cusps shows how
      many times the director becomes perpendicular to the I-N interface when one
      circumnavigates the closed boundary of the tactoid. We derive conservation laws
      that connect the number of cusps c to the topological strength m of defects in
      the N part of the simply connected and multiply connected tactoids. We
      demonstrate how the elastic anisotropy of the N phase results in non-circular
      shape of the disclination cores. A generalized Wulff construction is used to
      derive the shape of I and N tactoids as a function of I-N interfacial tension
      anisotropy in the approximation of frozen director field of various topological
      charges m. The complex shapes and structures of tactoids and topological defects
      demonstrate an important role of surface anisotropy in morphogenesis of phase
      transitions in liquid crystals. 

PMID- 24025850
TI  - Monitoring patient flow in emergency departments: the use of scatterplots versus
      time-based measures to assess patient flow in A&E.
AB  - OBJECTIVES: Care providers need accurate information to help them effectively
      manage patient flow in emergency departments (EDs) and deliver high-quality care
      within time constraints. Data should alert care providers to clinical risk and
      poor patient experience. In England, NHS A&E guidance proposes, among others,
      three measures to understand the distribution of waiting times in EDs - the
      median wait, 95th percentile and maximum wait. This study explores how well these
      three measures monitor performance and the potential added value of scatterplots.
      PATIENTS AND METHODS: Anonymized patient-level data on 463 000 patient visits
      collected over 2 full years recording length of stay to the nearest minute from
      four separate EDs were analysed. Scatterplots providing a detailed representation
      of the distribution of waiting times were produced for all sites. For each
      hospital, we explored how informative the scatterplots were compared with the
      single measures required under the NHS Outcomes Framework. RESULTS: There are
      several instances where the use of scatterplots adds value by identifying
      concerns that are not detected by the use of single measures alone. CONCLUSION:
      The use of scatterplots could help care providers better understand the
      distribution of waiting times in EDs, identify where EDs struggle to deliver care
      against time constraints and highlight poor patient experience and prompt action
      to address concerns.

PMID- 24025851
TI  - What is the 30-day rate of adverse cardiac events in chest pain patients with ED
      troponin I assays<=99th centile using a contemporary sensitive assay? An
      exploratory analysis.
AB  - AIM: For nonhigh-risk patients who 'rule out' for acute coronary syndrome,
      Australasian guidelines recommend further testing to identify coronary artery
      disease. Testing is usually performed as an outpatient procedure. This
      recommendation has not changed with the advent of sensitive biomarker assays. We
      aimed to determine the 30-day rate of adverse cardiac events in emergency
      department (ED) chest pain patients without known coronary artery disease who had
      ED troponin I (TnI) assays<=99th centile using a contemporary troponin assay,
      stratified by the Heart Foundation (HF; Australia) risk group. METHODS: This
      study is a substudy of a prospective observational study. Clinical and
      investigational data were collected. The primary outcome of interest was the
      proportion of patients with ED TnI assays<=99th centile who suffered a major
      adverse cardiac event (MACE; myocardial infarction, death, major arrhythmia)
      within 30 days, stratified by HF risk group. The secondary outcome was the rate
      of MACE or revascularization in non-HF high-risk patients. RESULTS: A total of
      460 patients were studied. Among them, 388 had no TnI assay>99th centile. There
      was one MACE in this group [0.26%, 95% confidence interval (CI) 0.05-1.5%]: a non
      ST segment elevation myocardial infarction in an HF high-risk patient. There were
      no MACEs among nonhigh-risk patients (0%, 95% CI 0-1.5%), and one patient had
      revascularization (0.4%; 95% CI 0.7-2.2%). CONCLUSION: Among ED patients
      presenting with suspected acute coronary syndrome, adverse cardiac events at 30
      days are rare in nonhigh-risk patients with contemporary TnI assays<99th centile.

PMID- 24025852
TI  - One hundred years of Arctic surface temperature variation due to anthropogenic
      influence.
AB  - Observations show that Arctic-average surface temperature increased from 1900 to
      1940, decreased from 1940 to 1970, and increased from 1970 to present. Here,
      using new observational data and improved climate models employing observed
      natural and anthropogenic forcings, we demonstrate that contributions from
      greenhouse gas and aerosol emissions, along with explosive volcanic eruptions,
      explain most of this observed variation in Arctic surface temperature since 1900.
      In addition, climate model simulations without natural and anthropogenic forcings
      indicate very low probabilities that the observed trends in each of these periods
      were due to internal climate variability alone. Arctic climate change has
      important environmental and economic impacts and these results improve our
      understanding of past Arctic climate change and our confidence in future
      projections. 

PMID- 24025853
TI  - Influence of the alkaline delignification on the simultaneous saccharification
      and fermentation (SSF) of sugar cane bagasse.
AB  - Ethanol production from steam explosion alkaline delignified bagasse was
      investigated by saccharification and simultaneous fermentation. Non delignified
      bagasse (ND) contained 25% lignin, and after alkaline delignification, materials
      with 6% (D1 - NaOH 1% w/v) and 12% (D05 - NaOH 0.5% w/v) lignin, respectively,
      were obtained. Ethanol production increased 450% and 733% in relation to ND, when
      D05 and D1 material, respectively, were used. Higher productivity and
      EtOH/bagasse were observed for D1. However, higher enzymatic convertibility of
      cellulose was obtained with 0.5% w/v NaOH. Alkaline delignification increased the
      ethanol production despite decreased cellulose.

PMID- 24025855
TI  - Expansion of the mutually exclusive spliced exome in Drosophila.
AB  - Mutually exclusive splicing is an important mechanism in a wide range of
      eukaryotic branches to expand proteome diversity, but the extent of its
      distribution within a single species and its evolutionary conservation is
      unknown. Here we present a genome-wide analysis of mutually exclusive spliced
      exons (MXEs) in Drosophila melanogaster at unprecedented depth. Most of the new
      MXE candidates are supported by evolutionary conservation, transcriptome data
      analysis and identification of competing RNA secondary structural elements. The
      enrichment of the genes with MXEs in transmembrane transporters and ion channel
      activity is consistent with findings in humans, although the MXEs appeared
      independently and in non-homologous genes, supporting the idea of a universal
      benefit of adapting ion channel and receptor properties by tandem exon
      duplications. The comparison of the mutually exclusive spliced exomes within the
      Drosophila clade shows high numbers of MXE gain and loss events, suggesting a
      role of these processes in speciation. 

PMID- 24025854
TI  - Purification and characterization of a new beta-glucosidase from Penicillium
      piceum and its application in enzymatic degradation of delignified corn stover.
AB  - A new beta-glucosidase (Cel3B) was first isolated from cellulytic fungi,
      designated as PpCel3B. Although PpCel3B was classified to GH family 3 based on
      the homology sequence, PpCel3B had different biological functions in cellulose
      degradation and signaling molecules production. PpCel3B was constitutive and
      could form multiple soluble lignocellulose inducers for cellulase and
      hemicellulase synthesis via high tranglycosylation activity and new enzymatic
      activity. Moreover, PpCel3B showed apparent synergism with cellulases by removing
      several inhibitors. Supplementing low doses of PpCel3B (52 MUg/g substrate)
      increased saccharification efficiency of cellulase produced by Trichoderma reesei
      and Penicillium piceum by 15% and 35%, respectively on delignified corn stover.
      PpCel3B had important application in boosting cellulase yield and efficiency.

PMID- 24025856
TI  - Photo competition as a tool for providing occupational health education to
      general secondary school students.
AB  - OBJECTIVES: Education on occupational health and safety (OHS) is not a compulsory
      part of the curriculum of general secondary schools (GSSs) in many countries.
      Adolescence is a formative period. Mainstreaming education in OHS into GSSs is
      necessary in order to initiate in students a risk prevention culture. We explored
      the feasibility of using a photo competition (PC) concerning health protection at
      work as a health education tool by assessing the degrees of relevant responses of
      students aged 13-18, teachers, parents and private enterprises and by identifying
      the types of work and hazards selected in 17 state and non-state GSSs of a Greek
      municipality. METHODS: Following the mayor's decision to hold a PC, prizes were
      secured from 11 private donors, the PC was publicized widely, and presentations
      on OHS were delivered to students by an occupational physician and suitably
      instructed teachers; the students then took photos of identifiable work
      situations containing OHS hazards, with protection either present or absent.
      Photos were assessed by juries of the Municipality and of the European Centre for
      the Environment and Health of the WHO. RESULTS: The 87 photos submitted revealed
      that students had an understanding of 15 types of OHS hazards, mainly knocks and
      blows (28.7%) and falls from heights (26.4%) but also of diseases (respiratory,
      back pain, hearing loss), in 28 types of non-school work, mostly in transport
      (12.6%) and construction (9.1%), and recognized measures for protection in 50.5%
      of photos. CONCLUSIONS: This PC concerning OHS in GSSs is the first reported in
      the literature, and it proved to be a feasible, extracurricular educational
      activity that requires increased teacher collaboration within the school
      curriculum.

PMID- 24025857
TI  - Prevalence of bile duct cancer among printing industry workers in comparison with
      other industries.
AB  - OBJECTIVES: The aim of this study was to assess the risk of developing bile duct
      cancer among workers in the other printing industry in comparison with workers in
      all industries in general. METHODS: Prevalence of bile duct cancer was compared
      between workers in the printing industry and age-standardized controls in all
      other industries using the claims database of the Japan Health Insurance
      Association, which insures workers of small-medium sized employers of all
      industries. RESULTS: Young (aged 30-49) male workers in the printing industry
      showed an elevated but insignificant standardized prevalence rate ratio (SPRR)
      for bile duct cancer in comparison with workers in all other industries (SPRR:
      1.78; 95%CI: 0.63-5.00). The risk was higher for intrahepatic bile duct cancer
      but remained insignificant (SPRR: 3.03; 95%CI: 0.52-17.56). CONCLUSIONS: The
      sharply elevated risk of bile duct cancer observed among proof-printing workers
      of a printing factory in Osaka may not be generalizable to workers in the
      printing industry nationwide.

PMID- 24025858
TI  - Sex differences in metabolism of trichloroethylene and trichloroethanol in guinea
      pigs.
AB  - OBJECTIVES: Trichloroethylene (TRI) has the potential to cause generalized
      dermatitis complicated with hepatitis. The guinea pig maximization test (GPMT)
      also suggests that both TRI and its metabolite trichloroethanol (TCE) exhibit
      immunogenicity and possible sex differences in guinea pigs. However, TRI and TCE
      metabolisms in guinea pigs have not been elucidated in detail. The first issue to
      clarify may be the sex differences in relation to the immunogenicity. METHODS: We
      collected urine from Hartley male and female guinea pigs 24 hours after
      intracutaneous injection of TRI, TCE or trichloroacetic acid (TCA) during a GPMT
      and measured the urinary metabolites by gas chromatography-mass spectrometry.
      RESULTS: After TRI treatment, the amount of TCA was significantly greater in
      females than males, while there was no sex difference in the total amount (TCA +
      TCE). TCA was only detected in urine after TCA treatment. Interestingly, not only
      TCE but also TCA was detected in urine of both sexes after TCE treatment, and the
      amount of TCA was also greater in females than males. An additional experiment
      showed that TCE treatment did not result in the detection of urinary TCA in
      cytochrome P450 (CYP)2E1-null mice TCEbut did in wild-type mice, suggesting the
      involvement of CYP2E1 in the metabolism from TCE to TCA. The constitutive
      expression of CYP2E1 in the liver of guinea pigs was greater in females than
      males. CONCLUSIONS: The sex difference in urinary TCA excretion after TRI and TCE
      treatments may be due to variation of the constitutive expression of CYP2E1.

PMID- 24025859
TI  - The relationship between occupational stress, burnout, and turnover intention
      among managerial staff from a Sino-Japanese joint venture in Guangzhou, China.
AB  - OBJECTIVE: The aim of this study was to analyze the associations between
      occupational stress, burnout and turnover intention and explore their associated
      factors among managerial staff in Guangzhou, China. METHODS: This cross-sectional
      study recruited 288 managerial employees from a Sino-Japanese joint venture
      automobile manufacturing enterprise in Guangzhou. The questionnaire included
      questions about sociodemographic characteristics, smoking, drinking and physical
      activity and the Chinese versio ns of the Occupational Stress Indicator (OSI),
      Maslach Burnout Inventory (MBI), Eysenck Personality Questionnaire (EPQ),
      Simplified Coping Style Questionnaire (SCSQ) and Social Support Rating Scale
      (SSRS). The response rate was 57.6%. Stepwise regression analysis was performed
      to examine the associations between burnout and occupational stress and turnover
      intention and related factors. RESULTS: The respondents had a high level burnout
      on the personal accomplishment subscale and had a high prevalence of turnover
      intention. Neuroticism, psychoticism, job satisfaction, occupational stress and
      social support were strong predictors of emotional exhaustion. Psychoticism,
      passive coping, occupational stress, objective support, utilization of support,
      male gender and job satisfaction were strong predictors of depersonalization.
      Active and passive coping and job satisfaction were strong predictors of personal
      accomplishment. Job dissatisfaction and emotional exhaustion were strong
      predictors of turnover intention. CONCLUSIONS: High occupational stress and low
      job satisfaction were associated with high burnout, particularly in the emotional
      exhaustion and depersonalization dimensions. Low job satisfaction and high
      emotional exhaustion were associated with high turnover intention among
      employees. Personality traits, social support and coping style were also found to
      be associated with burnout.

PMID- 24025860
TI  - Distribution of airborne bacteria in railway stations in Tokyo, Japan.
AB  - OBJECTIVES: We performed the current study to (1) understand the distribution of
      culturable airborne bacteria over a one-year monitoring period, (2) confirm
      places in stations where airborne bacteria are highly detected, (3) understand
      the factors that affect concentrations of airborne bacteria and (4) compare the
      distributions of airborne bacteria and fungi in railway stations in Japan.
      METHODS: Measurements of airborne bacteria were taken at stations A and B located
      in Tokyo. Station A had under- and above-ground concourses and platforms, whereas
      station B had spaces only above-ground. Airborne bacteria at each measurement
      position were collected with an air sampler on plate count agar media. After
      cultivation of the sampled media, the number of bacteria colonies was counted on
      each media. RESULTS: (1) Airborne bacteria were highly detected in the above
      ground concourse in station A. Almost all the indoor-to-outdoor (I/O) ratios of
      concentrations of airborne bacteria in the above-ground concourse in station A
      were higher than one throughout the year and were especially high in summer. (2)
      The factor that affects the concentrations of airborne bacteria seems to be the
      number of railway customers, not humidity. (3) The characteristics of the
      distributions of airborne bacteria and fungi were different, even though they
      were sampled in the same stations on the same days. CONCLUSIONS: In the case of
      controlling indoor air quality of stations in the future, the locations in
      railway stations that would require control of indoor air quality differ between
      airborne bacteria or fungi, respectively.

PMID- 24025861
TI  - Magnetic domain patterns on strong perpendicular magnetization of Co/Ni
      multilayers as spintronics materials: I. Dynamic observations.
AB  - Materials with perpendicular magnetic anisotropy can reduce the threshold current
      density of the current-induced domain wall motion. Co/Ni multilayers show strong
      perpendicular magnetic anisotropy and therefore it has become a highly potential
      candidate of current-induced domain wall motion memories. However, the details of
      the mechanism which stabilizes the strong perpendicular magnetization in Co/Ni
      multilayers have not yet been understood. In the present work, the evolution of
      the magnetic domain structure of multilayers consisting of pairs of 2 or 3
      monolayers (ML) of Ni and 1 ML of Co on W(110) was investigated during growth
      with spin-polarized low-energy electron microscopy. An interesting phenomenon,
      that the magnetic domain structure changed drastically during growth, was
      revealed. In the early stages of the growth the magnetization alternated between
      in-plane upon Co deposition and out-of-plane upon Ni deposition. The change of
      the magnetization direction occurred within a range of less than 0.2 ML during Ni
      or Co deposition, with break-up of the existing domains followed by growth of new
      domains. The Ni and Co thickness at which the magnetization direction switched
      shifted gradually with the number of Co/Ni pairs. Above 3-4 Co/Ni pairs it stayed
      out-of-plane. The results indicate clearly that the Co-Ni interfaces play the
      important role of enhancing the perpendicular magnetic anisotropy. 

PMID- 24025862
TI  - Volumetric evaluation of dual-energy perfusion CT for the assessment of
      intrapulmonary clot burden.
AB  - AIM: To evaluate the volumetric values of intrapulmonary clots (IPCs) using 64
      section dual-energy perfusion computed tomography (DEpCT). MATERIALS AND METHODS:
      A total of 174 patients suspected of having acute pulmonary embolism (PE)
      underwent DEpCT, and acute PE was diagnosed in 48 of these patients. DEpCT images
      were three-dimensionally reconstructed with four threshold ranges: 1-120 HU
      (V120), 1-15 HU (V15), 1-10 HU (V10), and 1-5 HU (V5). Each relative value per
      V120 was expressed as %V15, %V10 and %V5. These values were compared with the d
      dimer, pulmonary arterial (PA) pressure, right ventricular (RV) diameter, RV/left
      ventricular diameter ratio, PA diameter, and CT angiographic obstruction index
      (CTOI). RESULTS: In patients with IPCs, PA pressure, d-dimer and volumetric
      values of DEpCT were significantly higher (p < 0.001). Relative volumetric values
      at DEpCT had better correlations with the PA pressure, PA diameter, and CTOI than
      absolute ones, and %V5 especially had good correlations with PA pressure (r =
      0.44, p = 0.02), PA diameter (r = 0.40, p = 0.005), and CTOI (r = 0.38, p =
      0.009). CONCLUSION: The relative volumetric evaluation of DEpCT images with a
      lower attenuation threshold range may be helpful for assessing right heart
      strain, because these values had good correlation with CTOI, pulmonary pressure,
      and diameter in suggesting right heart load.

PMID- 24025863
TI  - Heart failure-induced changes of voltage-gated Ca2+ channels and cell
      excitability in rat cardiac postganglionic neurons.
AB  - Chronic heart failure (CHF) is characterized by decreased cardiac parasympathetic
      and increased cardiac sympathetic nerve activity. This autonomic imbalance
      increases the risk of arrhythmias and sudden death in patients with CHF. We
      hypothesized that the molecular and cellular alterations of cardiac
      postganglionic parasympathetic (CPP) neurons located in the intracardiac ganglia
      and sympathetic (CPS) neurons located in the stellate ganglia (SG) possibly link
      to the cardiac autonomic imbalance in CHF. Rat CHF was induced by left coronary
      artery ligation. Single-cell real-time PCR and immunofluorescent data showed that
      L (Ca(v)1.2 and Ca(v)1.3), P/Q (Ca(v)2.1), N (Ca(v)2.2), and R (Ca(v)2.3) types
      of Ca2+ channels were expressed in CPP and CPS neurons, but CHF decreased the
      mRNA and protein expression of only the N-type Ca2+ channels in CPP neurons, and
      it did not affect mRNA and protein expression of all Ca2+ channel subtypes in the
      CPS neurons. Patch-clamp recording confirmed that CHF reduced N-type Ca2+
      currents and cell excitability in the CPP neurons and enhanced N-type Ca2+
      currents and cell excitability in the CPS neurons. N-type Ca2+ channel blocker (1
      MUM omega-conotoxin GVIA) lowered Ca2+ currents and cell excitability in the CPP
      and CPS neurons from sham-operated and CHF rats. These results suggest that CHF
      reduces the N-type Ca2+ channel currents and cell excitability in the CPP neurons
      and enhances the N-type Ca2+ currents and cell excitability in the CPS neurons,
      which may contribute to the cardiac autonomic imbalance in CHF.

PMID- 24025864
TI  - Role of NADPH oxidase NOX5-S, NF-kappaB, and DNMT1 in acid-induced p16
      hypermethylation in Barrett's cells.
AB  - Inactivation of tumor suppressor genes via promoter hypermethylation may play an
      important role in the progression from Barrett's esophagus (BE) to esophageal
      adenocarcinoma (EA). We have previously shown that acid-induced p16 gene promoter
      hypermethylation may depend on activation of NADPH oxidase NOX5-S in BAR-T cells
      and OE33 EA cells. DNA methyltransferase 1 (DNMT1) is known to participate in
      maintaining established patterns of DNA methylation in dividing cells and may
      play an important role in the development of cancer. Therefore, we examined
      whether DNMT1 is involved in acid-induced p16 gene promoter hypermethylation in
      BAR-T cells. We found that the acid significantly increased p16 gene promoter
      methylation, decreased p16 mRNA, and increased cell proliferation, effects that
      may depend on activation of DNMT1 in BAR-T cells. DNMT1 is overexpressed in EA
      cells FLO and OE33 and EA tissues. Acid treatment upregulated DNMT1 mRNA
      expression and increased DNMT1 promoter activity. Acid-induced increases in DNMT1
      mRNA expression and promoter activity were significantly decreased by knockdown
      of NOX5-S and NF-kappaB1 p50. Conversely, overexpression of NOX5-S, p50, or p65
      significantly increased DNMT1 promoter activity. Knockdown of NOX5-S
      significantly decreased the acid-induced increase in luciferase activity in cells
      transfected with pNFkappaB-Luc. An NF-kappaB binding element GGGGTATCCC was
      identified in the DNMT1 gene promoter. We conclude that the acid-induced increase
      in p16 gene promoter methylation, downregulation of p16 mRNA, and increase in
      cell proliferation may depend on activation of DNMT1 in BAR-T cells. Acid-induced
      DNMT1 expression may depend on sequential activation of NOX5-S and NF-kappaB1
      p50.

PMID- 24025867
TI  - Evolution and cell physiology. 4. Why invent yet another protein complex to build
      junctions in epithelial cells?
AB  - The formation of the first epithelium was an essential step for animal evolution,
      since it has allowed coordination of the behavior of a cell layer and creation of
      a selective barrier between the internal medium and the outside world. The
      possibility of coupling the cells in a single layer has allowed morphogenetic
      events, such as tube formation, or gastrulation, to form more complex animal
      morphologies. The invention of sealed junctions between cells has allowed, on the
      other hand, creation of an asymmetry of nutrients or salts between the apical and
      the basal side of the epithelial layer. Creation of an internal medium has led to
      homeostasis, allowing the evolution of more complex physiological functions and
      the emergence of sophisticated animal shapes. During evolution, the origins of
      the first animals coincided with the invention of several protein complexes,
      including true cadherins and the polarity protein complexes. How these complexes
      regulate formation of the apicolateral border and the adherens junctions is still
      not fully understood. This review focuses on the role of these apical polarity
      complexes and, in particular, the Crumbs complex, which is essential for proper
      organization of epithelial layers from Drosophila to humans. 

PMID- 24025865
TI  - TRP channel Ca(2+) sparklets: fundamental signals underlying endothelium
      dependent hyperpolarization.
AB  - Important functions of the vascular endothelium, including permeability,
      production of antithrombotic factors, and control of vascular tone, are regulated
      by changes in intracellular Ca(2+). The molecular identities and regulation of
      Ca(2+) influx channels in the endothelium are incompletely understood, in part
      because of experimental difficulties associated with application of patch-clamp
      electrophysiology to native endothelial cells. However, advances in confocal and
      total internal reflection fluorescence microscopy and the development of fast,
      high-affinity Ca(2+)-binding fluorophores have recently allowed for direct
      visualization and characterization of single-channel transient receptor potential
      (TRP) channel Ca(2+) influx events in endothelial cells. These events, called
      "TRP channel Ca(2+) sparklets," have been optically recorded from primary
      endothelial cells and the intact endothelium, and the biophysical properties and
      fundamental significance of these Ca(2+) signals in vasomotor regulation have
      been characterized. This review will first briefly discuss the role of
      endothelial cell TRP channel Ca(2+) influx in endothelium-dependent vasodilation,
      describe improved methods for recording unitary TRP channel activity using
      optical methods, and highlight discoveries regarding the regulation and
      physiological significance of TRPV4 Ca(2+) sparklets in the vascular endothelium
      enabled by this new technology. Perspectives on the potential use of these
      techniques to evaluate changes in TRP channel Ca(2+) influx activity associated
      with endothelial dysfunction are offered.

PMID- 24025866
TI  - Histone deacetylase 6-mediated deacetylation of alpha-tubulin coordinates
      cytoskeletal and signaling events during platelet activation.
AB  - The tubulin cytoskeleton plays a key role in maintaining the characteristic
      quiescent discoid shape of resting platelets. Upon activation, platelets undergo
      a dramatic change in shape; however, little is known of how the microtubule
      system contributes to regulating platelet shape and function. Here we
      investigated the role of the covalent modification of alpha-tubulin by
      acetylation in the regulation of platelet physiology during activation.
      Superresolution microscopy analysis of the platelet tubulin cytoskeleton showed
      that the marginal band together with an interconnected web of finer tubulin
      structures collapsed upon platelet activation with the glycoprotein VI (GPVI)
      agonist collagen-related peptide (CRP). Western blot analysis revealed that alpha
      tubulin was acetylated in resting platelets and deacetylated during platelet
      activation. Tubacin, a specific inhibitor of the tubulin deacetylase HDAC6,
      prevented tubulin deacetylation upon platelet activation with CRP. Inhibition of
      HDAC6 upregulated tubulin acetylation and disrupted the organization of the
      platelet microtubule marginal band without significantly affecting platelet
      volume changes in response to CRP stimulation. HDAC6 inhibitors also inhibited
      platelet aggregation in response to CRP and blocked platelet signaling events
      upstream of platelet Rho GTPase activation. Together, these findings support a
      role for acetylation signaling in controlling the resting structure of the
      platelet tubulin marginal band as well as in the coordination of signaling
      systems that drive platelet cytoskeletal changes and aggregation. 

PMID- 24025869
TI  - N-(Aminobutyl)-N-(ethylisoluminol) and hemin dual-functionalized graphene hybrids
      with high chemiluminescence.
AB  - Herein, we report a facile strategy for the synthesis of dual-functionalized
      graphene hybrids (A-H-GNs) based on interactions among graphene, N-(aminobutyl)-N
      (ethylisoluminol) (ABEI) and hemin. The multilayers of a chemiluminescence
      reagent (ABEI) and a catalyst (hemin) were accumulated on the graphene surface,
      resulting in high chemiluminescence performance, good solubility and stability in
      aqueous solution. 

PMID- 24025868
TI  - Dystonia-associated protein torsinA is not detectable at the nerve terminals of
      central neurons.
AB  - Presynaptic functions of the mammalian central neurons are regulated by a network
      of protein interactions. Synaptic vesicle recycling in and neurotransmitter
      release from the presynaptic nerve terminals are altered when a glutamate
      deleting mutation is present in the torsinA protein (DeltaE-torsinA). This
      mutation is linked with a hereditary form of the movement disorder dystonia known
      as DYT1 dystonia. Although torsinA expression is prevalent throughout the central
      nervous system, its subcellular localization - in particular with respect to
      presynaptic nerve terminals - remains unclear. This information would be useful
      in narrowing down possible models for how wild-type torsinA affects presynaptic
      function, as well as the nature of the presynaptic dysfunction that arises in the
      context of DeltaE-torsinA mutation. Here we report on an analysis of the
      presynaptic localization of torsinA in cultured neurons obtained from a knock-in
      mouse model of DYT1 dystonia. Primary cultures of neurons were established from
      heterozygous and homozygous DeltaE-torsinA knock-in mice, as well as from their
      wild-type littermates. Neurons were obtained from the striatum, cerebral cortex
      and hippocampus of these mice, and were subjected to immunocytochemistry. This
      analysis revealed the expression of both proteins in the somata and dendrites.
      However, neither the nerve terminals nor axonal shafts were immunoreactive. These
      results were confirmed by fluorogram-based quantitation. Our findings indicate
      that neither the wild-type nor the DeltaE-torsinA mutant protein is present at
      substantial levels in the presynaptic structures of cultured neurons. Thus, the
      effects of torsinA, in wild-type and mutant forms, appear to influence
      presynaptic function indirectly, without residing in presynaptic structures. 

PMID- 24025870
TI  - Knowledge about prevention of oral cancer and gum disease among school teachers
      in Dharwad, India.
AB  - OBJECTIVE: To assess the knowledge of primary school teachers in Dharwad, India,
      regarding the prevention of oral cancer and gum disease. MATERIALS AND METHODS:
      In this cross sectional study a self administered questionnaire was used for data
      collection. A total of 184 school teachers were selected for the study. A
      response rate of 96.7% (n = 178) was obtained. RESULTS: Of the respondents, 36.5%
      (n = 65) had poor knowledge, while 27.5% had good knowledge regarding the
      prevention of oral cancer and gum disease. School teachers with postgraduate
      qualification were better informed with regard to the prevention of oral diseases
      as compared to those with only a bachelor degree. Factors such as education, sex,
      and type of institutional funding (public/private) were significantly correlated
      with the level of knowledge (R2 = 0.1128; P < 0.05). CONCLUSION: School teachers
      need to be motivated to improve their awareness and knowledge about the
      prevention of oral cancer and gum diseases, particularly the younger teachers and
      those with only bachelor degrees. Establishment of school-based oral-health
      promotion programs in India is urgently required.

PMID- 24025871
TI  - Prosthodontic status and needs of elderly institutionalized residents in
      Mangalore: a prospective study.
AB  - AIM: The aim of the present study is to assess the prevalence of Kennedy's
      classification, status of existing prosthodontic appliances if any, awareness of
      the subjects regarding various treatment options, and treatment needs in a group
      of elderly institutionalized residents. MATERIALS AND METHODS: The subjects were
      selected from various old age homes present in Mangalore city, with ages ranging
      from 60 to 80 years. The subjects were interviewed and examined by a single
      trained examiner and findings were recorded on a clinical case history report
      sheet. RESULTS: Kennedy's class I was most prevalent and class IV the least.
      Among the subjects examined, only 12.4% were wearing prosthesis. Based on the
      Nevalainen's index and Karslon's index, most of the prosthodontic appliances were
      found to be in poor condition. 86% of the subjects were in need of prosthodontic
      treatment. 75% of the subjects interviewed were unaware of the treatment options
      available. CONCLUSION: The elderly patients living in institutions do not achieve
      a deserving and satisfactory oral health care. The oral care assistance in
      institutionalized elderly patients has been an unfulfilled service.

PMID- 24025872
TI  - Prevalence of archaea in chronic periodontitis patients in an Indian population.
AB  - AIM: The aim of this study was to investigate the prevalence of archaea in the
      subgingival crevices of patients with chronic periodontitis in an Indian
      population. MATERIALS AND METHODS: Thirty four chronic periodontitis patients and
      16 healthy subjects were included in the study. Thirty four subgingival plaque
      samples were collected from chronic periodontitis patients, of which 17 samples
      were from deep pockets and 17 were from shallow pockets. Sixteen subgingival
      plaque samples were collected from healthy subjects. The presence of archaea in
      plaque samples was detected by polymerase chain reaction. RESULTS: Prevalence of
      archaea in chronic periodontitis patients was 29.4% and in healthy subjects was
      11.8%, which was not a statistically significant difference. However, prevalence
      of archaea, in deep periodontal pockets was 47.1%, in shallow periodontal pockets
      was 11.8% and in healthy sulcus was 12.5%, respectively. Thus, showing a
      statistically significant difference between prevalence of archaea in deep
      periodontal pockets (47.1%) and healthy sulcus (12.5%) and also between deep
      periodontal pockets (47.1%) and shallow pockets (11.8%), respectively.
      CONCLUSION: Archaea were detected commonly in severe periodontitis suggesting
      that these microorganisms might be involved in the pathogenesis of periodontal
      diseases.

PMID- 24025873
TI  - Evaluation of horizontal magnification on panoramic images.
AB  - AIMS: This study evaluated the horizontal magnification of images taken from
      adults and pediatrics with PM 2002 CC Planmeca analogue machine. MATERIALS AND
      METHODS: A series of 120 panoramic radiographs were obtained of 60 adults and 60
      pediatrics. For all patients, negative impressions were used to make positive
      casts of the teeth. A caliper was used to measure the maximum mesiodistal length
      of the buccal surface of all teeth except canines on both casts and radiographs.
      The horizontal magnification factor was calculated for incisor, premolar, and
      molar regions by dividing the values obtained from the casts by the values
      obtained from the radiographs. STATISTICAL ANALYSIS: Independent t-test and one
      way analysis of variance (ANOVA) were used. RESULTS: The results indicated that
      with regard to adults, maxillary and mandibular incisor regions, unlike the other
      two sessions, didn't show significant difference of the mean magnification of
      horizontal dimension (P = 0.5). In pediatrics, the comparison between mean
      magnification factors of all subgroups showed significant difference (P <
      0.0001). Despite the adults' radiographs, the results of pediatrics' radiographs
      showed significantly higher magnification than the index listed by the
      manufacturer of the radiographic machine used. CONCLUSION: The present study
      results point to the fact that PM 2002 CC Proline panoramic machine makes
      possible precise measurements on radiographs of adults' jaws in the horizontal
      dimension.

PMID- 24025874
TI  - Are more nickel ions accumulated in the hair of fixed orthodontic patients?
AB  - BACKGROUND AND OBJECTIVES: All elements existing in orthodontic alloys can be
      released to the oral cavity as corrosion products; therefore, they can accumulate
      in body tissues after systemic absorption. Among body tissues that can be
      evaluated for systemic absorption of nickel, in this study we used hair strands,
      because if nickel is absorbed systematically, it would accumulate in these
      strands over time. Furthermore, hair sampling is a non-invasive method, so the
      main aim of this study was the evaluation of nickel ions release into the hair
      strands of fixed orthodontic patients compared with the control group in a 4
      month duration. MATERIALS AND METHODS: In this clinical trial, the test group
      included 24 female patients between 12-20 years of age that were going to begin
      fixed orthodontic treatment. The control group consisted of their sisters in the
      same age range, who volunteered to participate in this study. Initial hair
      samples were taken from both groups at the beginning the study and immediately
      before setting up the fixed appliances in test group. The samples were taken from
      three different scalp sites including; frontal, vertex, and occipital areas.
      After 16 weeks, hair samples were taken from approximately the same scalp areas
      in both the groups. The samples were analyzed by atomic absorption
      spectrophotometer and data analyzed by Mann-Whitney test. RESULTS: This study
      showed that there were significant differences in nickel levels before and after
      study for case (P = 0.004) and control groups (P = 0.012). The mean nickel
      concentration after four months was 0.382 +/- 0.36 MUg/g for controls and 0.673
      +/- 0.38 MUg/g for the case group, which was significantly different (P = 0.002).
      CONCLUSION: The hair nickel concentrations significantly increased after
      insertion of fixed orthodontic appliances as compared with the control group.

PMID- 24025875
TI  - A comparative study of various decalcification techniques.
AB  - BACKGROUND: Study of fibrilar, cellular and sub cellular structures of
      mineralized tissues is only possible after the removal of the calcium apatite of
      these tissues by the process of demineralization. AIMS: The present study aims to
      evaluate six commonly used demineralizing agents to identify the best
      decalcifying agent. MATERIALS AND METHODS: The present study included six
      different decalcifying solutions: 10% formal nitric acid, 8% formal nitric acid,
      10% formic acid, 8% formic acid, Perenyi's fluid and Ethylene Di-Amine Tetra
      Acetic Acid. eight samples of posterior mandible of rat were decalcified in each
      of the decalcifying solutions and subjected to chemical end-point test. Ehrlich's
      Hematoxylin stain was used. STATISTICAL ANALYSIS USED: One way ANOVA was used for
      multiple group comparisons and Chi-square test was used for analyzing categorical
      data. P value of 0.05/less was set for statistical significance. RESULTS: Samples
      treated with EDTA showed the best overall histological impression and the tissue
      integrity were well preserved. Formal nitric of both the percentages 10 and 8%
      gave fairly good cellular detail and were rapid in their action. CONCLUSION: The
      final impression led to the proposition that EDTA was indeed the best
      decalcifying agent available. However, with time constraint, the use of formal
      nitric acid is advocated.

PMID- 24025876
TI  - Etiogenic study on oral lichenoid reactions among Tamil Nadu population: a
      prospective cohort study.
AB  - BACKGROUND: Most of the clinical, epidemiological, and etiogenic studies on oral
      lichenoid reactions (OLRs) have been undertaken in the United States, UK,
      Scandinavia, and other European countries. So far, very few cohort studies on a
      small population have been documented from South Asian region to implicate the
      role of various causative agents in the precipitation of OLR. OBJECTIVES: To
      implicate the role of various allopathic, alternate medicinal drugs, dental
      materials, etc., in the precipitation OLRs; to evaluate the pattern of remission;
      and to estimate the time period for the remission of lesions following the
      discontinuance of the suspected agents in the population of Tamil Nadu. MATERIALS
      AND METHODS: A total of 102 patients were included, of whom 51 (mean age 43.3
      years, SD 14.59) formed the study group, who possessed a positive drug history to
      the intake of either potential allopathic or alternate drugs or had recent dental
      metallic fillings/restorations, and 51 were (mean age 47.86 years, SD14.67) in
      the control group possessing oral lichen planus (OLP). The patients were followed
      up at a monthly interval period for a period of 18 months. RESULTS: Complete
      remission of signs and symptoms was noticed in 41 patients, partial remission in
      6, no change in 2, newer lesions in 1, and flaredup lesions were observed in 1
      participant in the study group. The mean onset time for lichenoid eruptions was
      found to be 2.5 months (SD 58.82) and the mean remission time after discontinuing
      the drug was 9.1 months (SD 4.7). CONCLUSION: OLR could be implicated to
      documented lichenoid agents like calcium channel blockers, ACE inhibitors,
      atarvastatin, metformin, glibenclamide, dapsone, carbimazole, silver amalgam
      fillings, etc.in southSouth Indian population. Furthermore, the drugs like
      oflaxacin, arsenical album, and yellow orpimentumwere also found to have strong
      implication in the precipitation of OLR. Discontinuance of the suspected agents
      resulted in healing in the majority of cases.

PMID- 24025877
TI  - A new technique to determine vertical dimension of occlusion from anthropometric
      measurements of fingers.
AB  - PURPOSE: The purpose of this study was to find the correlation between vertical
      dimension of occlusion (VDO) and length of fingers. MATERIALS AND METHODS: A
      cross-sectional study was conducted on 400 dentate subjects comprising of 200
      males and 200 females. Anthropometric measurements of VDO, length of index
      finger, length of little finger, and distance from tip of thumb to tip of index
      finger of right hand were recorded clinically using modified digital vernier
      caliper. Correlation between VDO and length of fingers was studied using
      Spearman's coefficient. For the execution of regression command and preparation
      of prediction equations to estimate VDO, Statistical Package for Social Sciences
      Software Version 11.5 was used. RESULTS: VDO was significantly and positively
      correlated with all the parameters studied. In males, correlation of VDO was
      strongest for length of index finger (r-0.406) whereas in females, it was
      strongest for length of little finger (r-0.385). VDO estimation using regression
      equation had a standard error of +/- 3.76 in males and +/- 2.86 in females for
      length of index finger, +/-3.81 and +/- 2.74 in males and females respectively
      for length of little finger, +/-3.99 and +/- 2.89 in males and females
      respectively for distance from tip of thumb to tip of index finger. CONCLUSIONS:
      Since the variations between VDO and finger lengths are within the range of 2-4
      mm, VDO prediction through this method is reliable, and reproducible. Also the
      method is simple, economic, and non-invasive; hence, it could be recommended for
      everyday practice.

PMID- 24025878
TI  - Evaluation of shear bond strength of three different types of artificial teeth to
      heat cure denture base resin: an in vitro study.
AB  - CONTEXT: Bonding of artificial teeth and denture base material remained a
      significant problem for successful prosthetic treatment. AIM: The purpose of this
      in vitro study was to evaluate shear bond strength of three different artificial
      teeth with heat cure denture base material after various surface conditioning
      methods and thermocycling. MATERIALS AND METHODS: Ninety mandibular first molar
      denture teeth were selected. They were divided into three groups, Group I:
      Nanocomposite resin (Veracia), Group II: Composite teeth (Endura), and Group III:
      Cross-linked acrylic denture teeth (Acry rock). All groups were further
      subdivided into subgroups based on surface conditioning methods. Subgroup A: No
      surface conditioning (control group), Subgroup B: Surface conditioning with
      methyl methacrylate-based bonding agent (Vitacoll), and Subgroup C: Air abrasion
      with 50 MUm aluminum oxide powder particles plus silane-coupling agent (Monobond
      S) and Vitacoll bonding agent. Evaluation of shear bond strength of all the
      specimens was done using universal testing machine. RESULTS: Mean shear bond
      strength of Group I, Subgroup B (6.87 +/- 0.934) showed higher value when
      compared with Group II, Subgroup B (6.76 +/- 1.84) and Group III, Subgroup B
      (5.66 +/- 2.18). The control group (untreated surface) of all three types of
      artificial teeth used in this study showed significantly lower shear bond
      strength values than experimental groups (surface conditioning methods; P <
      0.05). CONCLUSION: The results of this study suggest that there were significant
      differences in shear bond strength among control group and surface treatment
      groups of denture teeth bonded to heat cure denture base resin.

PMID- 24025879
TI  - The use of anatomical models for learning anesthesia techniques in oral surgery.
AB  - AIM: The objective of this work is to present a new collaborative method for
      teaching administration of anesthetic block in dentistry, with three-dimensional
      anatomical models used to improve learning and thereby increase safety, reduce
      anxiety, and improve the performance of students during the administration of
      anesthesia in the patients. MATERIALS AND METHODS: Three-dimensional (3D) models
      of skulls were made that reproduced all innervations of the V th cranial nerve
      (trigeminal nerve), as well as some blood vessels, glands, and muscles of
      mastication. For teaching the local anesthetic techniques we prepared pictures
      and videos of the administration of anesthesia in the models , which were
      presented to 130 students in two universities in Brazil. With the help of the
      models the students could follow the path of the nerves to be anesthetized and
      identify the anatomical points of reference for the correct positioning of the
      needle in the tissues. After the presentation the students answered a
      questionnaire aiming to assess the effect of the 3D models on learning. RESULTS:
      Eighty-eight percent of students rated the material as excellent, 12% as good, 0%
      as regular, and 0% as bad (unnecessary materials). After the presentation, 70% of
      the students felt confident about being able to achieve the nerve block in
      patients. CONCLUSION: When exposed to an appropriate method, students recognized
      the importance of knowledge of anatomy for learning local anesthetic techniques.
      This method improved the quality of education and increased patient safety during
      the first injection.

PMID- 24025880
TI  - Effect of different evaporation periods on microtensile bond strength of an
      acetone-based adhesive to dentin.
AB  - OBJECTIVE: Solvent content of a contemporary dental adhesive affect the bonding
      process, especially in the case of acetone based adhesives. The aim of this study
      was to evaluate the effect of different air-drying periods on microtensile bond
      strength (MTBS) of a total-etch adhesive to dentin. MATERIALS AND METHODS: Prime
      & Bond NT (Dentsply-USA) was used with different air-drying periods (0, 2, 5, 10,
      30sec) for bonding a composite resin to prepared dentin. The specimens were then
      subjected to a tensile force until fracture and the MTBSs of the samples were
      recorded. Failure modes of the fractured samples were also determined using
      stereomicroscope and scanning electron microscopy. Data were analyzed using ANOVA
      and Bonferroni tests (P = 0.05). RESULTS: With increasing the air-drying periods,
      the MTBSs were increased until the 5 second air-blowing; after that, with
      increasing the air-drying periods, the MTBSs decreased. Both, the most
      complicated failure and the strongest bond were seen in the 5 sec air-drying
      group. CONCLUSION: There is an optimum air-drying time for acetone based
      adhesives which results in the strongest bond to dentin.

PMID- 24025881
TI  - A comparison between various radiological techniques in the localization and
      analysis of impacted and supernumerary teeth.
AB  - BACKGROUND AND OBJECTIVES: An increasing number of different types of commercial
      cone-beam computed tomography (CBCT) devices are available for three-dimensional
      (3D) imaging in the field of dental and maxillofacial radiology. When removing
      impacted or supernumerary teeth, surgical teams often operate adjacent
      significant anatomical structures such as nerves, vessels, adjacent teeth roots,
      and paranasal sinuses. It is therefore important to choose the appropriate
      surgical approach to avoid iatrogenic damage to the essential anatomical
      neighbouring structures. CBCT, also called digital volume tomography (DVT), can
      visualize impacted and supernumerary teeth in all standard planes, as well as
      multisectional 3D views. These devices have shown to be highly beneficial in the
      assessment of small bony lesions and maxillofacial injuries. However, it is still
      necessary to determine the effectiveness of such devices in the assessment of
      impacted and supernumerary teeth, in comparison to the conventional radiological
      methods of intraoral X-rays and panoramic X-rays. MATERIALS AND METHODS: During a
      period of 2 years, a total of 61 patients of whom majority had impacted teeth or
      supernumerary elements in the frontal maxillary region were studied with CBCT and
      treated at the St. Olavs University Hospital. Patients were referred to our
      Department of Oral and Maxillofacial Surgery with both conventional and digital
      intraoral X-rays and/or panoramic X-rays. None had any acute infections or
      odontogenic abscesses, and most presented with asymptomatic impacted tooth. A
      comparison between the preoperative conventional and the CBCT images, the
      resulting diagnoses, and the intraoperative findings as "gold standard" were made
      and recorded in a compiled scoring sheet. The objects of interest were researched
      with the magnification method. Each patient was identified only with a patient
      number. RESULTS: In contrast to the conventional X-rays, the pre-surgical
      evaluation with the CBCT revealed detailed imaging of significant anatomical
      structures and objects of interest, with highly accurate anatomical and
      morphologic imaging, when compared to the intraoperative findings. Furthermore,
      no diagnostic problems, in relation to the anatomical localization, occurred
      preoperatively. CONCLUSION: The CBCT provides true and precise anatomical
      information with high surgical predictability without distortion or artefacts,
      and is superior to conventional radiography. It enables more time-efficient
      surgeries and reduces costs and surgical complications.

PMID- 24025882
TI  - Detection of putative periodontopathic bacteria in type 1 diabetic and healthy
      children: a comparative study.
AB  - AIM: The aim of this study was to compare and assess the risk of periodontitis
      due to the presence of four putative periodontopathic bacteria (Porphyromonas
      gingivalis, Treponema denticola, Tannerella forsythia, and Aggregatibacter
      actinomycetemcomitans) in type 1 diabetic and healthy children. MATERIALS AND
      METHODS: Fifty type 1 diabetic and 50 healthy children in the age group of 7-14
      years were recruited for the study. Subgingival plaque samples collected from
      permanent first molars were subjected to polymerase chain reaction assay to
      detect 16S rRNA gene of P. gingivalis, T. forsythia, T. denticola and A.
      actinomycetemcomitans. The data were analyzed using Fisher exact test. The P <
      0.05 was considered statistically significant. RESULTS: The prevalence of
      subgingival periodontal pathogens in diabetic and healthy children was 2% and 4%
      for P. gingivalis, 34% and 34% for T. denticola, 20% and 18% for A.
      actinomycetemcomitans and for T. forsythia, 4% and 34%, respectively. Significant
      statistical difference was not observed with regard to the prevalence of P.
      gingivalis, T. denticola, and A. actinomycetemcomitans among type 1 diabetic and
      healthy children (P = 1.00). Conversely, T. forsythia was less prevalent in
      diabetic children compared to healthy children. CONCLUSION: Statistical
      significance was not observed for the prevalence of periodontopathic bacteria in
      type 1 diabetic subjects. The results of the present study thus reveal the
      absence of risk of periodontitis by these bacterial species in type 1 diabetic
      subjects.

PMID- 24025883
TI  - Efficacy of spirulina as an antioxidant adjuvant to corticosteroid injection in
      management of oral submucous fibrosis.
AB  - BACKGROUND AND OBJECTIVES: Oral submucous fibrosis (OSF) is a chronic condition
      of the oral cavity which results in permanent disability. A number of studies
      have proven that the management of premalignant diseases should include
      antioxidants. Therefore, a study was carried out to evaluate the efficacy of
      spirulina as an antioxidant adjuvant to corticosteroid injections in the
      management of 40 oral submucous fibrosis subjects of south Karnataka and north
      Kerala. MATERIALS AND METHODS: An intervention study was conducted on 40 oral
      submucous fibrosis cases, 40 patients were divided into two groups, group A
      (spirulina group) and group B (placebo group). Group A received spirulina 500 mg
      twice daily and biweekly intralesional steroid injection of Betamethasone 4 mg/ml
      for 3 months and group B was given placebo capsules twice daily and biweekly
      intralesional steroid injection of Betamethasone 4 mg/ml for 3 months. The
      results were analyzed with the paired "t" test and the unpaired "t" test.
      RESULTS: Clinical improvements in mouth opening was significant in the
      posttreatment period in both Spirulina and placebo groups. Both the groups showed
      statistically significant reduction in burning sensation. However, when both
      groups were compared, mouth opening and burning sensation was found to be
      statistically very highly significant in favor of the spirulina group.
      CONCLUSION: Spirulina can bring about clinical improvements in OSF patients. The
      observed effects suggest that spirulina can be used as an adjuvant therapy in the
      initial management of OSF patients. However, studies involving larger samples and
      longer period of treatment follow up are suggested in the future.

PMID- 24025884
TI  - Changes of the upper lip in orthodontic and orthopedic treatment of angle's class
      II malocclusion.
AB  - AIMS: This study aimed to evaluate the changes in upper lips due to incisors
      retraction in Class II Division 1 patients treated with mandibular protraction,
      fixed appliances, and without extraction. MATERIALS AND METHODS: The sample
      consisted of 64 pre- and post-treatment lateral cephalometric X-rays of 32
      patients with 9-12 years old (16 men and 16 women), who presented ANB > 4 o ,
      overjet >= 4 mm, treated with Balter's Bionator and fixed appliances. The average
      period between initial and final radiographies was 5 years (maximum of 5.5 years
      and minimum of 4.5 years). STATISTICAL ANALYSIS USED: A Student's t-test (P <
      0.01) evaluated the statistical significance of differences between the mean
      values obtained for pre- and post-treatment in each variable, for males and
      females. Linear regression analysis for hard-tissue variables in relation to soft
      tissue variables were also made for correlation. RESULTS: The male group
      presented cervical point with r = 0.40 and incisal point with r = 0.42. Female
      subjects showed incisor cervical point with r = 0.86 and incisal point r = 0.74.
      The average Ls retraction was 0.55 mm in 2.43 mm of incisal point movement and
      0.34 mm of cervical point. The nasolabial angle showed increase average of 2
      degrees  for men and 3.9 degrees  for women. CONCLUSION: There is a difference
      between genders regarding the lip-incisor relation at this age. Males presented
      thickening of soft tissue and week correlation between the movement of the
      incisor and soft tissue both cervical and incisal point. In females' subjects, a
      strong correlation between the retraction movement and soft tissue, both cervical
      and incisal point.

PMID- 24025885
TI  - An in vitro study to compare the transverse strength of thermopressed and
      conventional compression-molded polymethylmethacrylate polymers.
AB  - STATEMENT OF PROBLEM: Acrylic resins have been in the center stage of
      Prosthodontics for more than half a century. The flexural fatigue failure of
      denture base materials is the primary mode of clinical failure. Hence there is a
      need for superior physical and mechanical properties. PURPOSE: This in vitro
      study compared the transverse strength of specimens of thermopressed injection
      molded and conventional compression-molded polymethylmethacrylate polymers and
      examined the morphology and microstructure of fractured acrylic specimens.
      MATERIALS AND METHODS: The following denture base resins were examined:
      Brecrystal (Thermopressed injection-molded, modified polymethylmethacrylate) and
      Pyrax (compression molded, control group). Specimens of each material were tested
      according to the American Society for Testing and Materials standard D790-03 for
      flexural strength testing of reinforced plastics and subsequently examined under
      SEM. The data was analyzed with Student unpaired t test. RESULTS: Flexural
      strength of Brecrystal (82.08 +/- 1.27 MPa) was significantly higher than Pyrax
      (72.76 +/- 0.97 MPa). The tested denture base materials fulfilled the
      requirements regarding flexural strength (>65 MPa). The scanning electron
      microscopy image of Brecrystal revealed a ductile fracture with crazing. The
      fracture pattern of control group specimens exhibited poorly defined
      crystallographic planes with a high degree of disorganization. CONCLUSION:
      Flexural strength of Brecrystal was significantly higher than the control group.
      Brecrystal showed a higher mean transverse strength value of 82.08 +/- 1.27 MPa
      and a more homogenous pattern at microscopic level. Based on flexural strength
      properties and handling characteristics, Brecrystal may prove to be an useful
      alternative to conventional denture base resins.

PMID- 24025886
TI  - Influence of finishing/polishing on color stability and surface roughness of
      composites submitted to accelerated artificial aging.
AB  - AIM: To assess the influence of finishing/polishing procedure on color stability
      (DeltaE ) and surface roughness (R(a)) of composites (Heliomolar and Tetric -
      color A2) submitted to accelerated artificial aging (AAA). MATERIALS AND METHODS:
      Sixty test specimens were made of each composite (12 mm * 2 mm) and separated
      into six groups (n = 10), according to the type of finishing/polishing to which
      they were submitted: C, control; F, tip 3195 F; FF, tip 3195 FF; FP, tip 3195 F +
      diamond paste; FFP, tip 3195 FF + diamond paste; SF, Sof-Lex discs. After
      polishing, controlled by an electromechanical system, initial color
      (spectrophotometer PCB 6807 BYK GARDNER) and R(a) (roughness meter Surfcorder SE
      1700, cut-off 0.25 mm) readings were taken. Next, the test specimens were
      submitted to the AAA procedure (C-UV Comexim) for 384 hours, and at the end of
      this period, new color readings and R(a) were taken. RESULTS: Statistical
      analysis [2-way analysis of variance (ANOVA), Bonferroni, P < 0.05] showed that
      all composites demonstrated DeltaE alteration above the clinically acceptable
      limits, with the exception of Heliomolar composite in FP. The greatest DeltaE
      alteration occurred for Tetric composite in SF (13.38 +/- 2.10) statistically
      different from F and FF (P < 0.05). For R(a), Group F showed rougher samples than
      FF with statistically significant difference (P < 0.05). CONCLUSION: In spite of
      the surface differences, the different finishing/polishing procedures were not
      capable of providing color stability within the clinically acceptable limits.

PMID- 24025888
TI  - Survival and complications of unconventional fixed dental prosthesis for
      maintaining diastema and splint pathologically migrated teeth: a case series up
      to 8 years follow-up.
AB  - Spacing in dentition negatively interferes with harmony of the smile. A lot of
      literature has been devoted to prosthetic closure of such space(s) in the
      dentition; however, the only option for maintaining space(s) in tooth-supported
      fixed dental prosthesis (FDP) is with the aid of loop connectors. Eleven patients
      (seven males and four females) with mean age of 45.18 years (range 22-70 years),
      previously treated with porcelain fused to metal full coverage restorations
      joined with loop connectors, were evaluated clinically to assess the clinical
      status and longevity of treatment provided. All the patients were asked to fill a
      simple close-ended questionnaire to provide their perspective on the limitations
      and outcome of the treatment and rate their satisfaction level on the scale of 1
      10. The cumulative survival of the FDPs with the aid of loop connectors was
      90.9%. There was no reported esthetic failure and, at the time of responding to
      the questionnaire, none of the patients had active complaint with respect to the
      prosthesis and all but one of the patients were satisfied with the treatment
      provided. Clinical survivability and the patient feedback suggests that
      customized designing of loop connectors for each patient is an excellent
      treatment modality to successfully maintain excessive (single/generalized)
      spacing between teeth and effectively splint pathologically migrated and mobile
      teeth. The reported problems with this treatment option are all transient in
      nature. 

PMID- 24025887
TI  - Immunohistochemical expression of protein 53, murine double minute 2, B-cell
      lymphoma 2, and proliferating cell nuclear antigen in odontogenic cysts and
      keratocystic odontogenic tumor.
AB  - INTRODUCTION: Even though odontogenic cysts share a similar histogenesis, they
      show different growth and differentiation profile due to differences in the
      proliferative cellular activity. AIMS: We perform an immunohistochemical
      assessment of protein 53 (p53), proliferating cell nuclear antigen (PCNA), B-cell
      lymphoma 2 (bcl-2), and murine double minute 2 (MDM2) expression in odontogenic
      cysts and keratocystic odontogenic tumor analyzing their correlation with the
      biological behavior of these lesions. MATERIALS AND METHODS: By the streptavidin
      biotin-peroxidase method with antibodies against p53, PCNA, bcl-2, and MDM2
      proteins, 11 radicular cysts, 11 dentigerous cysts, and 11 keratocystic
      odontogenic tumor were analyzed. The non-parametric Mann-Whitney U-test and
      Kruskall-Wallis test (P <= 0.05) were used to analyze the data. RESULTS:
      Immunopositivity for PCNA was observed in all cases appraised, predominantly in
      the suprabasal layer of keratocystic odontogenic tumor epithelial lining (SD +/-
      19.44), but no significant differences were found among the groups of lesions.
      Bcl-2 immunoexpression was observed especially in the basal layer of keratocystic
      odontogenic tumor. PCNA LI was significantly higher than bcl-2 LI in keratocystic
      odontogenic tumor. MDM2 and p53 immunoexpression were not detected in the lesions
      studied. Among the evaluated lesions, the keratocystic odontogenic tumor showed
      different immunoexpression of the proliferation and apoptosis markers.
      CONCLUSION: The results of this study suggest that the keratocystic odontogenic
      tumor presents distinct biological behavior of the odontogenic cysts, as for the
      processes of proliferation, apoptosis, and differentiation, reinforcing the
      information in favor of the neoplastic nature of this lesion.

PMID- 24025889
TI  - Submandibular swelling: tooth or salivary stone?
AB  - Submandibular swelling is a common clinical disorder of the maxillo-facial region
      that may be one of the manifestation of several pathologic disorders including
      sialolithiasis. A 38-year-old woman experienced a recurrent painful swelling in
      the right submandibular region for seven years. The symptoms, not always meal
      related, gradually became chronic and associated with dysphagia, odynophagia and
      fever. Ultrasonography of the salivary glands revealed a retained glandular
      structure and no ductal obstruction or dilatation, and orthopantomography showed
      the presence of a structure compatible with tooth, but these findings did not
      correlate with clinical scenario. Only CT dental scan identified the radiological
      image as a salivary stone. Sialolithiasis should always be considered in the
      diagnostic iter of painful submandibular swelling. A careful evaluation of
      recurrence and characteristics of signs and symptoms associated to the swelling
      can help in making the correct diagnosis and planning a proper therapeutic
      strategy. 

PMID- 24025890
TI  - B-cell lymphoma, unclassifiable, with features intermediate between diffuse large
      B-cell lymphoma and Burkitt lymphoma: report of a case in the oral cavity.
AB  - B-cell lymphoma, unclassifiable, with features intermediate between diffuse large
      B-cell lymphoma and Burkitt lymphoma (DLBCL/BL) is a new category of B-cell
      lymphoma according to the 4 th edition of the World Health Organization
      Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008). The
      following report presents a case of this rare, newly described entity on the
      palate of a 59 year-old male. 

PMID- 24025891
TI  - Van der Woude syndrome: report of two cases with supplementary findings.
AB  - Van der Woude syndrome (VWS) is a rare developmental disorder with an autosomal
      dominant inheritance and variable expressivity, occurring in about 1 of every
      1,00,000-2,00,000 people. This syndrome is remarkably variable. It is
      characterized by orofacial manifestations like lower lip pits, cleft lip and/or
      cleft palate, hypodontia, cleft or bifid uvula, syngnathia, narrow high arched
      palate, ankyloglossia and hyper nasal voice. We report two interesting cases of
      VWS with characteristic orofacial features and an unusual additional finding of
      bilateral commissural pits. The purpose of this article is to facilitate
      understanding of etio-pathogenesis, clinical manifestations, role of genetic
      counseling and with special emphasis on commissural pits as an additional feature
      in VWS. 

PMID- 24025892
TI  - Intraluminal plexiform hemangioameloblastomatous proliferation in unicystic
      ameloblastoma: an unusual case report.
AB  - The authors report a case of unicystic ameloblastoma with intraluminal plexiform
      hemangiomatous proliferation in the right mandible of an 18-year-old Indian male
      who suffered from painful swelling for 2 months. A radiograph showed a well
      circumscribed multilocular radiolucent lesion associated with the angle and ramus
      of the mandible. Microscopic examination revealed the cystic lesion lined with
      ameloblastic epithelium with intraluminal plexiform hemangioameloblastomatous
      proliferation. The possible pathogenic mechanism for hemangiomatous appearance of
      this case reflects the previous history of extraction. The prognosis is perhaps
      the same as expected for conventional unicystic ameloblastoma. 

PMID- 24025893
TI  - Nanobacteria in dental pulp stones.

PMID- 24025894
TI  - Effect of dental treatments on salivary immunoglobulin A of children with and
      without dental caries: a comparative study.
AB  - AIM: To evaluate and compare the effect of dental treatment on the salivary
      immunoglobulin A (IgA) levels of children with and without dental caries.
      MATERIALS AND METHODS: The study involved 30 children, among which 15 had caries
      and the other 15 were without caries. Salivary sample collection was done for all
      the children before dental treatment, and for the children with caries, the
      sampling was repeated 3-4 weeks after the dental treatment. The salivary IgA
      quantitation was done by enzyme-linked immunosorbent assay (ELISA), using Human
      IgA ELISA Quantitation kit, and the results were statistically analyzed by
      independent sample "t" test. RESULTS: The salivary IgA level was significantly
      more in children with caries (13.07 +/- 1.55 mg/100 ml) than in caries-free
      children (11.90 +/- 1.58 mg/100 ml) in the pre-treatment phase. The salivary IgA
      level in children with caries was 13.52 +/- 1.68 mg/100 ml in the post-treatment
      phase and it was not statistically different from the pre-treatment value.
      CONCLUSION: Mere quantitation of salivary IgA levels might have no reflection on
      the functional antibodies involved in caries process, and successful dental
      treatment alone does not alter the salivary IgA levels, suggesting a multifaceted
      approach to combat the cariogenic challenge.

PMID- 24025895
TI  - Assessment of gingival contours for esthetic diagnosis and treatment: a clinical
      study.
AB  - BACKGROUND: The purposes of this study were to quantify some clinical parameters
      that are useful as esthetic guidelines when the gingival contour is modified and
      to compare the left and right sides of the six maxillary anterior teeth.
      MATERIALS AND METHODS: Two hundred and forty interdental papilla sites in 20
      healthy patients were evaluated. Interdental papilla heights of maxillary
      anterior teeth were measured from the gingival zenith, along with clinical crown
      lengths. Percentages of papilla height to crown length were computed and defined
      as papilla proportion, mesial papilla proportion (MPP) and distal papilla
      proportion (DPP). RESULTS: Mean interdental papilla heights of maxillary teeth
      was 3.83 mm mesially and 3.8 mm distally. Mean MPP was 43.69% ( n = 120) and DPP
      was 44.57% ( n = 120). No significant differences were found between MPP and DPP
      for maxillary incisors ( P >= 0.5). CONCLUSION: Papilla proportions were
      approximately 44% for all tooth groups. Canines demonstrated a trend toward
      increased distal papilla heights. In the present study the average MPP and DPP of
      the central incisor (CI), lateral incisor (LI) and canine (CA) measured were 43%,
      41%, 46%, 40%, and 42% 51% respectively.

PMID- 24025896
TI  - Sealing ability of white and gray mineral trioxide aggregate mixed with distilled
      water and 0.12% chlorhexidine gluconate as a root end filling material: an ex
      vivo evaluation.
AB  - AIM: The aim of this study was to evaluate the sealing ability of white and gray
      mineral trioxide aggregate (MTA) mixed with distilled water and 0.12%
      chlorhexidine (CHX) gluconate when used as a root-end filling material using the
      dye-penetration technique. MATERIALS AND METHODS: A total of 48 single-rooted
      human teeth were cleaned, shaped, and obturated with gutta-percha and AH Plus
      sealer. The apical 3 mm of each root was resected, and 3-mm deep root-end cavity
      preparations were made. The teeth were randomly divided into 4 experimental
      groups, each containing 8 teeth, and 2 negative and positive control groups, each
      containing 8 teeth. Root-end cavities in the experimental groups were filled with
      the experimental materials. After application of nail polish, the teeth were
      exposed to India ink for 72 h and longitudinally sectioned, and the extent of dye
      penetration was measured with a stereomicroscope. RESULTS: No statistically
      significant differences were observed in the sealing ability of gray and white
      MTA mixed with distilled water and 0.12% CHX. CONCLUSION: CHX appears to be a
      good alternative to replace distilled water, as a solution to be mixed with MTA.

PMID- 24025897
TI  - Sarjeev's supernumerary tooth notation system: a universally compatible add-on to
      the Two-Digit system.
AB  - AIM: To give notation for quadrants, tooth position, and the type of
      supernumerary teeth for both permanent and deciduous dentition. Tooth numbering
      provides dentists with an essential shortcut in clinical record keeping.
      MATERIALS AND METHODS: Three systems are favored worldwide: the Zsigmondy/Palmer
      system, the Universal system, and the Federation Dentaire Internationale (FDI)
      Two-Digit system. Histories of all tooth-numbering methods were traced and the
      strengths and deficiencies of each system were reviewed. The FDI Two-Digit system
      is widely used throughout the world, except USA, and is the only method that
      makes the visual sense, cognitive sense, and computer sense. CONCLUSION: On
      review it was noticed that all tooth notation systems in vogue have a drawback as
      they do not provide any information or notations for supernumerary teeth such as
      paramolar, distomolar, mesiodens, and fused teeth.

PMID- 24025898
TI  - Herpes zoster of trigeminal nerve after dental extraction.
AB  - Herpes zoster is an uncommon acute viral infection caused by reactivation of
      varicella zoster virus. During the prodromal stage, the only presenting symptom
      may be odontalgia, which may prove to be a diagnostic challenge for the dentist.
      Practicing dentist may carry out emergency treatment that might result in
      irreversible damage or may delay the appropriate treatment. With an ever
      increasing number of elderly and immunocompromised patients reporting to the
      dentist, the dental profession can expect to encounter an increased number of
      herpes zoster patients. Dentist must be familiar with the presenting signs and
      symptoms of patients experiencing the prodromal manifestations of herpes zoster
      of the trigeminal nerve. This article focuses on the difficulties in management
      of such cases, and one such case is reported here. 

PMID- 24025899
TI  - Frequency of resistance in obligate anaerobic bacteria isolated from dogs, cats,
      and horses to antimicrobial agents.
AB  - Clinical specimens from dogs, cats, and horses were examined for the presence of
      obligate anaerobic bacteria. Of 4,018 specimens cultured, 368 yielded 606
      isolates of obligate anaerobic bacteria (248 from dogs, 50 from cats, and 308
      from horses). There were 100 specimens from 94 animals from which only anaerobes
      were isolated (25 dogs, 8 cats, and 61 horses). The most common sites tested were
      abdominal fluid (dogs and cats) and intestinal contents (horses). The most common
      microorganism isolated from dogs, cats, and horses was Clostridium perfringens
      (75, 13, and101 isolates, respectively). The MICs of amoxicillin with
      clavulanate, ampicillin, chloramphenicol, metronidazole, and penicillin were
      determined using a gradient endpoint method for anaerobes. Isolates collected at
      necropsy were not tested for antimicrobial susceptibility unless so requested by
      the clinician. There were 1/145 isolates tested that were resistant to
      amoxicillin-clavulanate (resistance breakpoint >= 16/8 MUg/ml), 7/77 isolates
      tested were resistant to ampicillin (resistance breakpoint >= 2 MUg/ml), 4/242
      isolates tested were resistant to chloramphenicol (resistance breakpoint >= 32
      MUg/ml), 12/158 isolates tested were resistant to clindamycin (resistance
      breakpoint >= 8 MUg/ml), 10/247 isolates tested were resistant to metronidazole
      (resistance breakpoint >= 32 MUg/ml), and 54/243 isolates tested were resistant
      to penicillin (resistance breakpoint >= 2 MUg/ml). These data suggest that
      anaerobes are generally susceptible to antimicrobial drugs in vitro. 

PMID- 24025900
TI  - Changing swabs: to validate or not to validate?

PMID- 24025902
TI  - Novel fastidious, partially acid-fast, anaerobic Gram-positive bacillus
      associated with abscess formation and recovered from multiple medical centers.
AB  - We report a novel anaerobe causing abscess in four patients at three hospitals.
      In the clinical specimen, bacilli were branching, Gram positive, and acid fast.
      The organism grew slowly and was not identified by 16S rRNA sequencing. Our
      findings support the description of a new genus and species of the suborder
      Corynebacterineae. 

PMID- 24025903
TI  - Clostridium difficile genotypes in piglet populations in Germany.
AB  - Clostridium difficile was isolated from 147 of 201 (73%) rectal swabs of piglets
      from 15 farms of Lower Saxony and North Rhine-Westphalia. In 14 farms, 14 to 100%
      (mean, 78%) of the animals tested were culture positive. The rate of isolation
      was 68% postpartum, increased to 94% in animals 2 to 14 days of age, and declined
      to 0% for animals 49 days of age and older. There was no link between isolation
      and antibiotic treatment or diarrhea of piglets. Strains were assigned to 10 PCR
      ribotypes, and up to 4 PCR ribotypes were found to be present at the same time on
      a farm. The closely related PCR ribotypes 078 (55%) and 126 (20%) were most
      frequently recovered and were present in 13 of the 14 positive farms. The
      comparison of multilocus VNTR (variable number of tandem repeats) analysis (MLVA)
      data from this study and previously published data on human, porcine, and bovine
      PCR ribotype 078 isolates from 5 European countries revealed genetic differences
      between strains of different geographic origin and confirmed the relatedness of
      human and porcine C. difficile isolates. This study demonstrated that the human
      pathogenic PCR ribotypes 078 and 126 are predominant in piglets in Germany. The
      results suggest that presence of C. difficile is correlated with animal age but
      not with antibiotic treatment or clinical disease. MLVA indicated that strains of
      the same geographical origin are often genetically related and corroborated the
      hypothesis of a close epidemiological connection between human and porcine C.
      difficile isolates. 

PMID- 24025901
TI  - Diversity of methicillin-resistant Staphylococcus aureus strains isolated from
      residents of 26 nursing homes in Orange County, California.
AB  - Nursing homes represent a unique and important methicillin-resistant
      Staphylococcus aureus (MRSA) reservoir. Not only are strains imported from
      hospitals and the community, strains can be transported back into these settings
      from nursing homes. Since MRSA bacteria are prevalent in nursing homes and yet
      relatively poorly studied in this setting, a multicenter, regional assessment of
      the frequency and diversity of MRSA in the nursing home reservoir was carried out
      and compared to that of the MRSA from hospitals in the same region. The
      prospective study collected MRSA from nasal swabbing of residents of 26 nursing
      homes in Orange County, California, and characterized each isolate by spa typing.
      A total of 837 MRSA isolates were collected from the nursing homes. Estimates of
      admission prevalence and point prevalence of MRSA were 16% and 26%, respectively.
      The spa type genetic diversity was heterogeneous between nursing homes and
      significantly higher overall (77%) than the diversity in Orange County hospitals
      (72%). MRSA burden in nursing homes appears largely due to importation from
      hospitals. As seen in Orange County hospitals, USA300 (sequence type 8
      [ST8]/t008), USA100 (ST5/t002), and a USA100 variant (ST5/t242) were the dominant
      MRSA clones in Orange County nursing homes, representing 83% of all isolates,
      although the USA100 variant was predominant in nursing homes, whereas USA300 was
      predominant in hospitals. Control strategies tailored to the complex problem of
      MRSA transmission and infection in nursing homes are needed in order to minimize
      the impact of this unique reservoir on the overall regional MRSA burden. 

PMID- 24025904
TI  - High similarity of novel orthoreovirus detected in a child hospitalized with
      acute gastroenteritis to mammalian orthoreoviruses found in bats in Europe.
AB  - Mammalian orthoreoviruses (MRVs) are known to cause mild enteric and respiratory
      infections in humans. They are widespread and infect a broad spectrum of mammals.
      We report here the first case of an MRV detected in a child with acute
      gastroenteritis, which showed the highest similarity to an MRV reported recently
      in European bats. An examination of a stool sample from the child was negative
      for most common viral and bacterial pathogens. Reovirus particles were identified
      by electron microscopic examination of both the stool suspension and cell culture
      supernatant. The whole-genome sequence was obtained with the Ion Torrent next
      generation sequencing platform. Prior to sequencing, the stool sample suspension
      and cell culture supernatant were pretreated with nucleases and/or the convective
      interaction medium (CIM) monolithic chromatographic method to purify and
      concentrate the target viral nucleic acid. Whole-genome sequence analysis
      revealed that the Slovenian SI-MRV01 isolate was most similar to an MRV found in
      a bat in Germany. High similarity was shared in all genome segments, with
      nucleotide and amino acid identities between 93.8 to 99.0% and 98.4 to 99.7%,
      respectively. It was shown that CIM monolithic chromatography alone is an
      efficient method for enriching the sample in viral particles before nucleic acid
      isolation and next-generation sequencing application. 

PMID- 24025905
TI  - Evaluation of pneumococcal serotyping by multiplex PCR and quellung reactions.
AB  - Screening of 1,750 pneumococcal isolates for common serotypes by PCR was followed
      by Quellung reaction analysis of PCR-negative isolates with a comparison to the
      conventional (Quellung reaction only) approach. PCR agreed with Quellung reaction
      results for 99% of isolates. The sequential PCR/Quellung reaction algorithm is
      accurate and more cost-effective than the conventional approach. 

PMID- 24025906
TI  - Publisher's expression of concern: geographical differences associated with SNPs
      in nine gene targets among resistant clinical isolates of Mycobacterium
      tuberculosis.
AB  - The American Society for Microbiology (ASM) and the Journal of Clinical
      Microbiology (JCM) are issuing this Expression of Concern to alert readers to
      questions about the ownership of the data in the following publication: M.
      Hoshide, L. Qian, C. Rodrigues, R. Warren, T. Victor, H. B. Evasco II, T. Tupasi,
      V. Crudu, and J. T. Douglas. Geographic Differences Associated with SNPs in Nine
      Gene Targets among Resistant Clinical Isolates of Mycobacterium tuberculosis. J.
      Clin. Microbiol. Published ahead of print 19 June 2013. doi:10.1128/JCM.00857-13.
      JCM has been notified that substantial portions of the data presented in the
      manuscript were derived from results of a multicenter study centered at the
      University of California in San Diego (UCSD) and funded by the National
      Institutes of Health, and that the manuscript by Hoshide et al. was submitted for
      publication without prior approval of the UCSD study center. This matter is now
      under discussion by the University of Hawaii, Dr. Douglas's institution, and
      UCSD. Pending resolution of the questions raised regarding the right of the
      authors to publish these data, JCM has placed publication of the final version of
      the manuscript on hold. It should be noted that, according to ASM policies
      prohibiting duplicate publication, while the Hoshide et al. manuscript remains
      published, JCM cannot consider papers from other participants in the multicenter
      study if they include essentially the same data.

PMID- 24025907
TI  - Multicenter evaluation of a commercial cytomegalovirus quantitative standard:
      effects of commutability on interlaboratory concordance.
AB  - Commutability of quantitative reference materials has proven important for
      reliable and accurate results in clinical chemistry. As international reference
      standards and commercially produced calibration material have become available to
      address the variability of viral load assays, the degree to which such materials
      are commutable and the effect of commutability on assay concordance have been
      questioned. To investigate this, 60 archived clinical plasma samples, which
      previously tested positive for cytomegalovirus (CMV), were retested by five
      different laboratories, each using a different quantitative CMV PCR assay.
      Results from each laboratory were calibrated both with lab-specific quantitative
      CMV standards ("lab standards") and with common, commercially available standards
      ("CMV panel"). Pairwise analyses among laboratories were performed using mean
      results from each clinical sample, calibrated first with lab standards and then
      with the CMV panel. Commutability of the CMV panel was determined based on
      difference plots for each laboratory pair showing plotted values of standards
      that were within the 95% prediction intervals for the clinical specimens.
      Commutability was demonstrated for 6 of 10 laboratory pairs using the CMV panel.
      In half of these pairs, use of the CMV panel improved quantitative agreement
      compared to use of lab standards. Two of four laboratory pairs for which the CMV
      panel was noncommutable showed reduced quantitative agreement when that panel was
      used as a common calibrator. Commutability of calibration material varies across
      different quantitative PCR methods. Use of a common, commutable quantitative
      standard can improve agreement across different assays; use of a noncommutable
      calibrator can reduce agreement among laboratories. 

PMID- 24025908
TI  - Risk factors for campylobacteriosis in two washington state counties with high
      numbers of dairy farms.
AB  - Campylobacteriosis is a frequently reported, food-borne, human bacterial disease
      that can be associated with ruminant reservoirs, although public health messages
      primarily focus on poultry. In Washington State, the two counties with the
      highest concentrations of dairy cattle also report the highest incidences of
      campylobacteriosis. Conditional logistic regression analysis of case-control data
      from both counties found living or working on a dairy farm (odds ratio [OR], 6.7
      [95% confidence interval [CI], 1.7 to 26.4]) and Hispanic ethnicity (OR, 6.4 [95%
      CI, 3.1 to 13.1]) to have the strongest significant positive associations with
      campylobacteriosis. When the analysis was restricted to residents of one county,
      Hispanic ethnicity (OR, 9.3 [95% CI, 3.9 to 22.2]), contact with cattle (OR, 5.0
      [95% CI, 1.3 to 19.5]), and pet ownership (OR, 2.6 [95% CI, 1.1 to 6.3]) were
      found to be independent risk factors for disease. Campylobacter jejuni isolates
      from human (n = 65), bovine (n = 28), and retail poultry (n = 27) sources from
      the same counties were compared using multilocus sequence typing. These results
      indicated that sequence types commonly found in human isolates were also commonly
      found in bovine isolates. These findings suggest that, in areas with high
      concentrations of dairy cattle, exposure to dairy cattle may be more important
      than food-borne exposure to poultry products as a risk for campylobacteriosis. 

PMID- 24025909
TI  - Splenic abscess caused by Streptococcus gallolyticus subsp. pasteurianus as
      presentation of a pancreatic cancer.
AB  - Splenic abscesses caused by Streptococcus bovis are rarely reported in the
      literature and are mainly seen in patients with endocarditis and associated
      colonic neoplasia/carcinoma. We report the first case of splenic abscess caused
      by Streptococcus gallolyticus subsp. pasteurianus (Streptococcus bovis biotype
      II/2) as presentation of a pancreatic cancer. 

PMID- 24025911
TI  - Conjunctivitis caused by Neisseria gonorrhoeae isolates with reduced
      cephalosporin susceptibility and multidrug resistance.
AB  - We report two cases of conjunctivitis caused by Neisseria gonorrhoeae with
      reduced cephalosporin susceptibility. Patients showed no response to cefmenoxime
      eye drops and intravenous ceftriaxone administration. The patients' condition
      improved after the addition of oral minocycline. The isolates contained the
      mosaic penA for reduction of beta-lactam susceptibility. 

PMID- 24025910
TI  - Scopulariopsis, a poorly known opportunistic fungus: spectrum of species in
      clinical samples and in vitro responses to antifungal drugs.
AB  - Ninety-nine isolates of clinical origin, tentatively identified as Scopulariopsis
      or Microascus, were morphologically and molecularly characterized by a combined
      analysis of the D1/D2 domains of the 28S rRNA gene and a fragment of the
      elongation factor 1-alpha gene (EF1-alpha) sequences. The most prevalent species
      was Scopulariopsis brevicaulis (49.4%), followed by Scopulariopsis gracilis
      (14.4%), Scopulariopsis brumptii (7.2%), Microascus cinereus (5.2%), the
      Scopulariopsis candida species complex (3.1%), and Microascus cirrosus (2.1%).
      The most common anatomic sites of isolation were the respiratory tract (61.6%),
      superficial tissue (19.2%), and deep tissue or fluid samples (19.2%). The
      antifungal susceptibilities of the isolates to eight drugs were tested in vitro,
      with all the drugs generally showing poor activity. 

PMID- 24025912
TI  - Actinomyces urogenitalis bacteremia and tubo-ovarian abscess after an in vitro
      fertilization (IVF) procedure.
AB  - We describe the first case of bacteremia due to Actinomyces urogenitalis.
      Bacteremia was secondary to a tubo-ovarian abscess following transvaginal oocyte
      retrieval. Identification was established by matrix-assisted desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by 16S
      rRNA gene sequencing. A. urogenitalis should be considered as a potential
      causative agent of infection after gynecological procedures. 

PMID- 24025913
TI  - Male-specific W4P/R mutation in the pre-S1 region of hepatitis B virus,
      increasing the risk of progression of liver diseases in chronic patients.
AB  - The issue of hepatitis B virus (HBV) mutations possibly leading to a gender
      disparity in the progression of liver diseases has not been explored. We aimed to
      elucidate the relationships of the novel pre-S1 mutations, W4P/R, with the
      progression of liver diseases and male predominance in a South Korean chronic
      cohort by use of a molecular epidemiologic study. We developed a fluorescence
      resonance energy transfer (FRET)-based real-time PCR (RT-PCR) assay for the
      detection of the W4P/R mutations and applied it to 292 chronic HBV patients. The
      pre-S1 mutations from 247 (84.6%) of a total of 292 patients were detected by
      this assay. W4P/R mutants were found to be significantly related to severe liver
      diseases (hepatocellular carcinoma [HCC] and liver cirrhosis, 12.4% [19/153] of
      patients, versus chronic hepatitis and asymptomatic carriage, 1.1% [1/94] of
      patients) (P < 0.001). All of the W4P/R mutants were found in males only. The
      novel HBV pre-S1 mutations, W4P/R, may be associated with disease severity in
      male patients chronically infected with HBV genotype C. The W4P/R mutations may
      provide in part an explanation for the relatively high ratio of male to female
      incidence in HCC generation in South Korean chronic HBV patients. 

PMID- 24025914
TI  - International multicenter evaluation of the DiversiLab bacterial typing system
      for Escherichia coli and Klebsiella spp.
AB  - Successful multidrug-resistant clones are increasing in prevalence globally,
      which makes the ability to identify these clones urgent. However, adequate, easy
      to-perform, and reproducible typing methods are lacking. We investigated whether
      DiversiLab (DL), an automated repetitive-sequence-based PCR bacterial typing
      system (bioMerieux), is suitable for comparing isolates analyzed at different
      geographic centers. A total of 39 Escherichia coli and 39 Klebsiella species
      isolates previously typed by the coordinating center were analyzed. Pulsed-field
      gel electrophoresis (PFGE) confirmed the presence of one cluster of 6 isolates,
      three clusters of 3 isolates, and three clusters of 2 isolates for each set of
      isolates. DL analysis was performed in 11 centers in six different countries
      using the same protocol. The DL profiles of 425 E. coli and 422 Klebsiella spp.
      were obtained. The DL system showed a lower discriminatory power for E. coli than
      did PFGE. The local DL data showed a low concordance, as indicated by the
      adjusted Rand and Wallace coefficients (0.132 to 0.740 and 0.070 to 1.0 [E. coli]
      and 0.091 to 0.864 and 0.056 to 1.0 [Klebsiella spp.], respectively). The central
      analysis showed a significantly improved concordance (0.473 to 1.0 and 0.290 to
      1.0 [E. coli] and 0.513 to 0.965 and 0.425 to 1.0 [Klebsiella spp.],
      respectively). The misclassifications of profiles for individual isolates were
      mainly due to inconsistent amplification, which was most likely due to variations
      in the quality and amounts of the isolated DNA used for amplification. Despite
      local variations, the DL system has the potential to indicate the occurrence of
      clonal outbreaks in an international setting, provided there is strict adherence
      to standardized, reproducible DNA isolation methods and analysis protocols, all
      supported by a central database for profile comparisons. 

PMID- 24025915
TI  - Incidence of inducible clindamycin resistance in Staphylococcus pseudintermedius
      from dogs.
AB  - Clindamycin is increasingly used to treat canine pyoderma. Eight of 608
      Staphylococcus pseudintermedius isolates were positive for inducible clindamycin
      resistance by double-disk diffusion testing and PCR detection of ermB.
      Staphylococcus pseudintermedius isolates that are erythromycin resistant but
      clindamycin susceptible by in vitro antimicrobial susceptibility testing should
      be tested for inducible clindamycin resistance. 

PMID- 24025916
TI  - Obstructive sleep apnea: strategies for minimizing liability and enhancing
      patient safety.
AB  - OBJECTIVE: To characterize malpractice litigation regarding obstructive sleep
      apnea (OSA) and educate physicians on frequently cited factors. STUDY DESIGN AND
      SETTING: Analysis of the Westlaw legal database. METHODS: Jury verdict and
      settlement reports were examined for outcome, awards, patient demographic
      factors, defendant specialty, and alleged causes of malpractice. RESULTS: Out of
      54 identified cases, 33 (61.1%) cases were resolved in favor of defendants, 12
      (22.2%) via settlement, and 9 (16.7%) through jury award. Median settlement and
      jury awards did not significantly differ ($750,000 vs $550,000, P > .50). Age and
      gender did not affect outcome. Otolaryngologists and anesthesiologists were the
      most frequently named defendants. Forty-seven cases (87.1%) stemmed from OSA
      patients who underwent procedures with resultant perioperative adverse events.
      Common alleged factors included death (48.1%), permanent deficits (42.6%),
      intraoperative complications (35.2%), requiring additional surgery (25.9%),
      anoxic brain injury (24.1%), inadequate informed consent (24.1%), inappropriate
      medication administration (22.2%), and inadequate monitoring (20.4%). CONCLUSION:
      Litigation related to OSA is frequently associated with perioperative
      complications more than nonoperative issues such as a failure to diagnose this
      disorder. Nonetheless, OSA is considerably underdiagnosed, and special attention
      should be paid to at-risk patients, including close monitoring of their clinical
      status and the medications they receive. For patients with diagnosed or suspected
      OSA with planned operative intervention, whether for OSA or an unrelated issue, a
      comprehensive informed consent process detailing the factors outlined in this
      analysis is an effective strategy to increase communication and improve the
      physician-patient relationship, minimize liability, and ultimately improve
      patient safety.

PMID- 24025917
TI  - 18F-fluorodeoxyglucose uptake pattern in patients with suspected
      spondylodiscitis.
AB  - BACKGROUND: Infections of the spine are rare and often discovered late, but they
      can have a severe outcome with hospital case fatality rates of up to 17%.
      Efficient and early diagnosis is important, because early diagnosis and therapy
      improve outcome. The aim of the current study was to evaluate the clinical value
      of F-fluorodeoxyglucose (18F-FDG) uptake pattern in PET as a diagnostic modality
      for the detection of spondylodiscitis. MATERIALS AND METHODS: 18F-FDG-PET
      examinations of the spine were performed in 42 patients with suspected
      spondylodiscitis. Of these 42 patients, 13 had already undergone spinal surgery
      in the past, making initial definition of the test group difficult and complex.
      Qualitative analysis was based on 18F-FDG uptake patterns, and quantitative
      maximal standard uptake value measurements were ascertained. PET findings were
      verified by comparing them with combined information from intraoperative
      findings, blood results, microbiological investigations, histopathology, and
      clinical examination. RESULTS: Evidence of spondylodiscitis was correctly
      determined in 95% of patients and absence of spondylodiscitis in 86% of patients
      using 18F-FDG-PET. The detection of spondylodiscitis by 18F-FDG-PET had a
      sensitivity of 86% and a specificity of 95%. Three patients had false-negative
      and one patient a false-positive finding on 18F-FDG-PET. CONCLUSION: The
      application of 18F-FDG uptake patterns in 18F-FDG-PET helps to predict or exclude
      spondylodiscitis. Differentiation between inflammatory and degenerative changes
      in the vertebral body endplates is possible. Owing to the high specificity of
      this method, a negative PET result in the setting of a diagnostically unclear
      case diminishes the need for surgical intervention. 18F-FDG-PET is therefore an
      important tool in inflammation imaging and can be used in the diagnostic cascade
      of difficult cases with suspected spondylodiscitis. In contrast, a positive PET
      result does not always clearly establish the cause of increased 18F-FDG uptake.

PMID- 24025919
TI  - Correlation of 18F-fluorodeoxyglucose uptake with histopathological prognostic
      factors in breast carcinoma.
AB  - OBJECTIVE: This study investigated the prognostic value of [18F]
      fluorodeoxyglucose (18F-FDG) uptake in breast carcinomas by comparing 18F-FDG
      PET/computed tomography (CT) images with histopathological and
      immunohistochemical prognostic factors. METHODS: This study included 136 women
      and four men with positive biopsy breast carcinomas who underwent 18F-FDG PET/CT
      imaging for initial staging. Maximum standardized uptake values (SUVmax) and
      tumour-to-background SUVmax ratios were calculated and compared with
      histopathological and immunohistochemical tumour characteristics, patient
      properties and axillary lymph node involvement. Calculations of SUVmax for men
      were performed separately. RESULTS: For the tumours in women, the mean SUVmax was
      10.06+/-6.91 and the median SUVmax was 9.05 (0.7-35.0). Primary tumour 18F-FDG
      uptake and tumour-to-background SUVmax ratios were correlated with tumour size
      (P<0.001), histological type (P<0.001), histological grade (P=0.004),
      pleomorphism (P=0.010), mitosis count (P<0.001), lymphatic invasion (P=0.009),
      necrosis (P=0.005), oestrogen negativity (P=0.004), high Ki-67 level (P<0.001),
      axillary lymph node involvement (P<0.001) and triple negativity (P=0.002). High
      Ki-67 level (odds ratio=16; 95% confidence interval=1.6-160; P=0.016) and tumour
      size (odds ratio=4; 95% confidence interval=1.5-11; P=0.007) were determining
      factors for high 18F-FDG uptake values. Other clinicopathological and
      immunohistopathological parameters including progesterone receptor (P=0.211),
      CerbB2 overexpression (P=0.170), perineural invasion (P=0.053), intratumoural
      calcification (P=0.438), desmoplasia (P=0.112), tubular formation (P=0.768) and
      age (P=0.675) were not significantly correlated with 18F-FDG uptake. No
      significant relationship was observed between the tumour/contralateral breast
      SUVmax ratio and mitotic count, oestrogen receptor status or triple negativity.
      CONCLUSION: F-FDG uptake may serve as a prognostic indicator for biological
      behaviour in breast tumours.

PMID- 24025918
TI  - rhTSH-aided low-activity versus high-activity regimens of radioiodine in residual
      ablation for differentiated thyroid cancer: a meta-analysis.
AB  - The effects of low-activity versus high-activity radioiodine regimens in thyroid
      remnant ablation for patients with differentiated thyroid carcinoma (DTC) under
      recombinant human thyrotropin (rhTSH) stimulation have been widely quoted but
      there has been no systematic review of the evidence. We undertook a systematic
      review of randomized controlled trials to assess the effects of low-activity
      radioiodine in thyroid remnant ablation in patients with DTC under rhTSH
      stimulation compared with high-activity radioiodine. Studies were obtained from
      computerized searches of MEDLINE, EMBASE, and the Cochrane Library (all until
      September 2012). Randomized controlled trials were included. Altogether, 637
      patients with DTC who participated in three trials for residual ablation were
      included. Overall, studies had a low risk of bias. We found no statistically
      significant differences between low-activity (1.11/1.85 GBq) and high-activity
      (3.7 GBq) radioiodine treatment aided by rhTSH in terms of successful ablation
      rates on the basis of diagnostic scans [odds ratio (OR) 0.85, 95% confidence
      interval (CI) 0.49-1.47, P=0.56], thyroglobulin levels (OR 0.66, 95% CI 0.38
      1.15, P=0.14), and health-related quality of life (mean difference 0.07, 95% CI 
      0.96 to 1.09, P=0.9). In addition, the subgroup analysis of 1.11 versus 3.7 GBq
      (OR 0.83, 95% CI 0.46-1.49, P=0.53) and 1.85 versus 3.7 GBq (OR 1, 95% CI 0.23
      4.35, P=1) also showed no significant differences. The lower activity of 1.11 GBq
      showed significant benefit in terms of reduction in adverse events including neck
      pain, radiation gastritis, and salivary dysfunction during and after ablation (OR
      0.63, 95% CI 0.42-0.93, P=0.02). Limited data from three randomized controlled
      trials suggested that an rhTSH-aided low radioiodine activity level of as low as
      1.115 GBq may be sufficient for thyroid remnant ablation when compared with 3.7
      GBq, with fewer common adverse effects in patients with metastasis-free DTC.
      Further evidence is needed to confirm the effects of low-activity radioiodine for
      thyroid remnant ablation. Radioiodine treatment of 1.11 GBq showed significant
      benefit in terms of reduction in adverse events including neck pain, radiation
      gastritis, and salivary dysfunction during and after ablation (OR 0.63, 95% CI
      0.42-0.93, P=0.02). rhTSH-aided low radioiodine activity levels of 1.11 and 1.85
      GBq are sufficient for thyroid remnant ablation as compared with 3.7 GBq, with
      fewer common adverse effects in patients with metastasis-free DTC. A well
      designed study that compares low-activity with high-activity radioiodine ablation
      is needed to fully understand the long-term adverse effects and relapse or
      metastases.

PMID- 24025920
TI  - 13N-Ammonia PET/CT for detection of recurrent glioma: a prospective comparison
      with contrast-enhanced MRI.
AB  - PURPOSE: We assessed the value of N-ammonia PET-computed tomography (PET/CT) in
      recurrent glioma and compared the results with those of contrast-enhanced MRI (CE
      MRI). MATERIALS AND METHODS: Fifty-two (mean age, 39.8+/-11.6 years; male, 33;
      female, 19) histopathologically proven and previously treated glioma patients
      with clinical suspicion of recurrence were evaluated with 13N-ammonia PET/CT and
      CE MRI. PET/CT images were evaluated qualitatively and quantitatively (maximum
      standardized uptake value). Tumour to white matter (T/W), tumour to grey matter
      (T/G) and tumour to pituitary (T/P) ratios were calculated and cutoff levels were
      derived with receiver operating characteristic curve analysis. Sensitivity,
      specificity and predictive values were compared. A combination of clinical follow
      up, repeat imaging and biopsy (when available) was taken as the reference
      standard. RESULTS: On the basis of the reference standard, 23 out of 52 patients
      were seen to have recurrence. Overall sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy of 13N-ammonia PET/CT
      were 82.6, 86.2, 82.6, 86.2 and 84.6%, respectively, whereas those of CE MRI were
      96.7, 48.3, 59.5, 93.3 and 69.2%, respectively. Overall, 13N-ammonia PET/CT was
      statistically superior to CE MRI (P=0.001). In low-grade tumours, 13N-ammonia
      PET/CT performed better than MRI with an accuracy of 86.8 versus 68.4% (P=0.003).
      In high-grade tumours, both the modalities had comparable performances with
      accuracies of 78.6% for N-ammonia PET/CT and 71.4% for CE MRI (P=0.250). Among
      the ratios, T/P was the most useful, with the largest area under the curve
      (0.825; P=0.0001). CONCLUSION: N-Ammonia PET/CT shows higher accuracy compared
      with contrast-enhanced MRI for detecting recurrent gliomas, particularly in low
      grade tumours.

PMID- 24025921
TI  - Diameter-dependent ion transport through the interior of isolated single-walled
      carbon nanotubes.
AB  - Nanopores that approach molecular dimensions demonstrate exotic transport
      behaviour and are theoretically predicted to display discontinuities in the
      diameter dependence of interior ion transport because of structuring of the
      internal fluid. No experimental study has been able to probe this diameter
      dependence in the 0.5-2 nm diameter regime. Here we observe a surprising fivefold
      enhancement of stochastic ion transport rates for single-walled carbon nanotube
      centered at a diameter of approximately 1.6 nm. An electrochemical transport
      model informed from literature simulations is used to understand the phenomenon.
      We also observe rates that scale with cation type as Li(+)>K(+)>Cs(+)>Na(+) and
      pore blocking extent as K(+)>Cs(+)>Na(+)>Li(+) potentially reflecting changes in
      hydration shell size. Across several ion types, the pore-blocking current and
      inverse dwell time are shown to scale linearly at low electric field. This work
      opens up new avenues in the study of transport effects at the nanoscale.

PMID- 24025922
TI  - Imaging of pediatric renal transplants and their complications: a pictorial
      review.
AB  - Renal transplantation is the treatment of choice for end-stage renal disease in
      children. As a technically demanding surgery with complex medical management, it
      is associated with a number of complications. Anatomic imaging including
      ultrasonography with color and spectral Doppler and functional assessment with
      renal perfusion scintigraphy are complementary for the detection and
      characterization of posttransplant complications. Complications can be
      characterized by the time of appearance after transplantation (immediate, early,
      or late) or the anatomic site of origin (perinephric, vascular, urologic, or
      renal parenchymal). Perinephric fluid collections include hematomas and seromas,
      abscesses, lymphoceles, and urinomas. Noninfected collections frequently resolve
      spontaneously but should be monitored to exclude progression. Vascular
      complications are more prevalent in pediatric patients because of the small
      vessel caliber and include vascular thrombosis and stenosis. Arteriovenous
      fistulas and pseudoaneurysms can complicate biopsy and are typically transient.
      Common urologic complications include urine leak and urinary tract obstruction.
      Renal perfusion scintigraphy can be invaluable in elucidating the nature of such
      complications. Renal parenchymal abnormalities include acute tubular necrosis,
      rejection, and toxic effects of medication. Imaging features of renal parenchymal
      abnormalities can overlap, and the primary role of imaging is to exclude
      alternative causes of renal dysfunction. Renal and nonrenal mass lesions are more
      common in immunosuppressed patients after transplantation. Familiarity with the
      normal imaging appearance of the renal allograft and the appearances of common
      complications facilitates accurate diagnosis and timely treatment, with the
      ultimate goal of increasing graft survival. This goal is particularly crucial in
      children, given their greater number of projected life years.

PMID- 24025923
TI  - Imaging of juvenile idiopathic arthritis: a multimodality approach.
AB  - Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases
      characterized by synovial inflammation and is the most common rheumatic complaint
      in children. To facilitate research and treatment, JIA has been further
      classified on the basis of the number of joints involved, additional symptoms,
      family history, and serologic findings. Imaging in patients with JIA has
      historically relied on radiography, which allows the accurate assessment of
      chronic changes of JIA, including growth disturbances, periostitis, and joint
      malalignment. However, radiographic findings of active inflammation are
      nonspecific, and, in the past, clinical evaluation has taken precedence over
      imaging of acute disease. Recent advances in disease-modifying therapeutic agents
      that can help prevent long-term disability in patients with JIA have led to
      greater emphasis on the detection of early joint-centered inflammation that
      cannot be accurately assessed radiographically and may not be evident clinically.
      Both contrast material-enhanced magnetic resonance (MR) imaging and Doppler
      ultrasonography (US) are well suited for this application and are playing an
      increasingly important role in diagnosis, risk stratification, treatment
      monitoring, and problem solving. Contrast-enhanced MR imaging is the most
      sensitive technique for the detection of synovitis and is the only modality that
      can help detect bone marrow edema, both of which indicate active inflammation. US
      is more sensitive than radiography for the detection of synovial proliferation
      and effusions and is particularly useful in the evaluation of small peripheral
      joints. The complexity of the temporomandibular and sacroiliac joints limits the
      usefulness of radiographic or US evaluation, and contrast-enhanced MR imaging is
      the preferred modality for evaluation of these structures.

PMID- 24025925
TI  - FDG PET of the brain in pediatric patients: imaging spectrum with MR imaging
      correlation.
AB  - Positron emission tomography (PET) of the brain is an important problem-solving
      tool in pediatric neuroimaging, neurology, and neurosurgery. Fluorine 18
      fluorodeoxyglucose (FDG) PET or dual-modality PET and computed tomographic (CT)
      imaging (PET/CT), with magnetic resonance (MR) imaging correlation, can be used
      to evaluate childhood epilepsy and pediatric brain tumors, areas in which PET
      adds value in patient management. FDG PET has been widely used in pediatric
      temporal lobe epilepsy, most commonly manifesting as mesial temporal sclerosis,
      which demonstrates hypometabolism at interictal PET and hypermetabolism during
      seizures. Recently, FDG PET has shown added value for patients with extratemporal
      epilepsy, in whom FDG PET can help identify cortical foci of interictal
      hypometabolism that are undetectable or difficult to detect with MR imaging.
      These findings can then guide additional investigations and surgery. FDG PET also
      enhances medical decision making in children with brain tumors, in whom FDG PET
      can be used to (a) improve the diagnostic yield of stereotactic biopsies by
      detecting metabolically active areas of tumor, (b) help guide the surgeon in
      achieving total tumor resection, and (c) increase detection of residual or
      recurrent tumor. Technologic advances in the past decade have allowed fusion of
      PET and MR images, combining the high resolution of MR imaging with the low
      resolution functional capability of PET. As dual-modality integrated PET/MR
      imaging systems become available, CT coregistration for PET can be eliminated,
      thus reducing patient radiation exposure. Increasing familiarity with normal and
      abnormal appearances of FDG PET brain images correlated with MR images can
      enhance diagnostic yield and improve the care of children with epilepsy and brain
      tumors.

PMID- 24025926
TI  - Multispectral quantitative MR imaging of the human brain: lifetime age-related
      effects.
AB  - Quantitative magnetic resonance (MR) imaging allows visualization of age-related
      changes in the normal human brain from functional, biochemical, and morphologic
      perspectives. Findings at quantitative MR imaging support age-related
      microstructural changes in the brain: (a) volume expansion, increased
      myelination, and axonal growth, which establish neural connectivity in
      neurodevelopment, followed by (b) volume loss, myelin breakdown, and axonal
      degradation, leading to the disruption of neural integrity later in life. A rapid
      growth change followed by a continuous slower change in quantitative MR
      parameters can be modeled with a logarithmic or exponential decay function. The
      age dependencies during adulthood often fit a quadratic model for transitional
      changes with accelerated aging effects or a linear model for steady
      changes.Understanding these general trends over the human life span can improve
      assessment for a specific disease by helping determine appropriate study
      settings. Once a consensus on acquisition techniques and image processing
      algorithms has been reached, quantitative MR imaging can play an important role
      in the assessment of disease states affecting the brain. 

PMID- 24025927
TI  - Response criteria in oncologic imaging: review of traditional and new criteria.
AB  - There has been a proliferation and divergence of imaging-based tumor-specific
      response criteria over the past 3 decades whose purpose is to achieve objective
      assessment of treatment response in oncologic clinical trials. The World Health
      Organization (WHO) criteria, published in 1981, were the first response criteria
      and made use of bidimensional measurements of tumors. The Response Evaluation
      Criteria in Solid Tumors (RECIST) were created in 2000 and revised in 2009. The
      RECIST criteria made use of unidimensional measurements and addressed several
      pitfalls and limitations of the original WHO criteria. Both the WHO and RECIST
      criteria were developed during the era of cytotoxic chemotherapeutic agents and
      are still widely used. However, treatment strategies changed over the past
      decade, and the limitations of using tumor size alone in patients undergoing
      targeted therapy (including arbitrarily determined cutoff values to categorize
      tumor response and progression, lack of information about changes in tumor
      attenuation, inability to help distinguish viable tumor from nonviable
      components, and inconsistency of size measurements) necessitated revision of
      these criteria. More recent criteria that are used for targeted therapies include
      the Choi response criteria for gastrointestinal stromal tumor, modified RECIST
      criteria for hepatocellular carcinoma, and Immune-related Response Criteria for
      melanoma. The Cheson criteria and Positron Emission Tomography Response Criteria
      in Solid Tumors make use of positron emission tomography to provide functional
      information and thereby help determine tumor viability. As newer therapeutic
      agents and approaches become available, it may be necessary to further modify
      existing anatomy-based response-assessment methodologies, verify promising
      functional imaging methods in large prospective trials, and investigate new
      quantitative imaging technologies.

PMID- 24025928
TI  - Patterns of nonmasslike enhancement at screening breast MR imaging of high-risk
      premenopausal women.
AB  - Current U.S. recommendations for breast cancer screening of women with at least a
      20%-25% lifetime risk of developing breast cancer include contrast material
      enhanced magnetic resonance (MR) imaging of the breasts. The cancer detection
      rate in high-risk women undergoing screening MR imaging is approximately 10 times
      higher than that in normal-risk women undergoing screening mammography. Many of
      these high-risk women commence MR imaging screening while they are premenopausal,
      when the breasts are most influenced by cyclical hormonal changes. Healthy
      premenopausal breast tissue enhances in a cyclical and variable manner. This
      enhancement is described as background enhancement. Typically, enhancement of
      normal breast tissue occurs in a symmetric and diffuse pattern, and there is
      little diagnostic difficulty in classifying it as normal background parenchymal
      enhancement. However, sometimes the pattern is more focal, asymmetric, or
      regional. It may then be described as nonmasslike enhancement, an observation
      associated with both benign and malignant breast pathologic conditions. A review
      of the morphologic features and internal enhancement patterns in normal but
      nondiffuse background enhancement and abnormal nonmasslike enhancement in high
      risk premenopausal women can help improve interpretive specificity and decrease
      false-positive interpretations. MR imaging pitfalls and interpretation strategies
      for localized background enhancement and pathologic nonmasslike enhancement in
      this high-risk population are highlighted. In evaluating nonmasslike enhancement,
      the use of the Breast Imaging Reporting and Data System (BI-RADS) lexicon to
      perform careful analysis of morphologic features, along with an understanding of
      the role and limitations of kinetic information, will help balance early breast
      cancer detection against false-positive interpretation.

PMID- 24025929
TI  - Second-look US: how to find breast lesions with a suspicious MR imaging
      appearance.
AB  - Breast magnetic resonance (MR) imaging has high sensitivity in breast cancer
      diagnosis. The probability of malignancy for additional detected lesions is
      higher in patients with breast cancer than in the population without malignancy,
      which is why biopsy or further study should be considered for additional detected
      lesions. Because of the shortcomings of MR imaging-guided biopsy, second-look
      ultrasonography (US) may be the preferred next step. Detecting target lesions at
      second-look US and correlating lesions between the two modalities may be
      challenging. Using axial MR imaging to localize the lesion with respect to the
      nipple and the lesion-to-nipple distance can narrow the scan range at US.
      Evaluating the lesion's location relative to the mammary zones and surrounding
      tissues, as well as noting its depth, characteristics, and nearby landmarks, will
      aid in lesion correlation. Doppler imaging, tissue harmonic imaging, and other US
      techniques can be used to identify subtle lesions. Although malignant breast
      lesions may appear probably benign at second-look US, decision making for biopsy
      must be based primarily on MR imaging findings. In sonographically occult, MR
      imaging-detected lesions with suspicious MR imaging features, the probability of
      malignancy is much higher than 2%, and MR imaging-guided biopsy must be
      performed.

PMID- 24025930
TI  - AIRP best cases in radiologic-pathologic correlation: malignant phyllodes tumor
      with osteosarcomatous differentiation.

PMID- 24025931
TI  - MR imaging of myocardial infarction.
AB  - Magnetic resonance (MR) imaging plays an important role in evaluation of various
      aspects of myocardial infarction (MI). MR imaging is useful in establishing the
      diagnosis of acute MI, particularly in patients who present with symptoms of MI
      but outside the diagnostic time frame of altered cardiac enzyme levels or with
      clinical features of acute MI but without an angiographic culprit lesion. MR
      imaging is valuable in establishing a diagnosis of chronic MI and distinguishing
      this condition from nonischemic cardiomyopathies, mainly through use of delayed
      enhancement patterns. MR imaging also provides clinicians with several prognostic
      indicators that enable risk stratification, such as scar burden, microvascular
      obstruction, hemorrhage, and peri-infarct ischemia. The extent and transmurality
      of scar burden have been shown to have independent and incremental prognostic
      power over a range of left ventricular function. The extent of scarring at MR
      imaging is an important predictor of successful outcome after revascularization
      procedures, and extensive scarring in the lateral wall indicates poor outcome
      after cardiac resynchronization therapy. Scar size at MR imaging is also a useful
      surrogate end point in clinical trials. Finally, MR imaging can be used to detect
      complications of MI, such as aneurysms, pericarditis, ventricular septal defect,
      thrombus, and mitral regurgitation. Supplemental material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.335125722/-/DC1.

PMID- 24025932
TI  - AIRP best cases in radiologic-pathologic correlation: cardiac echinococcus
      infection.

PMID- 24025933
TI  - Spectrum of multilocular cystic hepatic lesions: CT and MR imaging findings with
      pathologic correlation.
AB  - A multilocular cystic hepatic lesion detected at computed tomography (CT) and
      magnetic resonance (MR) imaging is a common but nonspecific radiologic finding
      that can cause potential challenges for differential diagnosis. This imaging
      pattern may be observed in a wide spectrum of common and uncommon neoplastic or
      nonneoplastic entities. Neoplastic lesions include cystadenoma,
      cystadenocarcinoma, hepatocellular carcinoma (HCC), metastases, mesenchymal
      hamartoma, and inflammatory myofibroblastic tumor. Nonneoplastic lesions include
      hepatic abscess, echinococcal cyst, intrahepatic hematoma, and biloma. The
      multiple coalescent cysts seen in polycystic liver disease may exhibit an imaging
      pattern similar to that of a multilocular cystic lesion. Mural nodularity,
      irregular thickness of the septa, ragged inner surface, and typical enhancement
      pattern in the solid portion of the lesion are often indicative of malignancy,
      although multilocular primary or secondary malignant tumors are uncommon.
      Recognition of the more common necrosis or cystic change of HCC and metastases
      induced by locoregional or systemic treatment also is important. The nonenhanced
      cystic component may be composed of different types of fluids (eg, serous,
      mucinous, proteinaceous, hemorrhagic, bilious, or mixed) or spontaneous or
      treatment-related necrosis, whereas the septa may be formed by a wide range of
      tissues depending on the lesion type. An understanding of the CT and MR imaging
      findings of these lesions and their respective pathologic correlation aids in
      accurate diagnosis. 

PMID- 24025934
TI  - Injury of the gluteal aponeurotic fascia and proximal iliotibial band: anatomy,
      pathologic conditions, and MR imaging.
AB  - The fascia lata, or deep fascia of the thigh, is a complex anatomic structure
      that has not been emphasized as a potential source of pelvic and hip pain. This
      structure represents a broad continuum of fibrous tissue about the buttock, hip,
      and thigh that receives contributions from the posteriorly located aponeurotic
      fascia covering the gluteus medius muscle and from the more laterally located
      iliotibial band (ITB). At the pelvis and hip, the ITB consists of three layers
      that merge at the lower portion of the tensor fasciae latae muscle. The gluteal
      aponeurotic fascia and ITB merge at the buttock and hip before extending
      inferiorly to the Gerdy tubercle at the anterolateral tibia. Injuries to these
      anatomic structures are an underdiagnosed cause of pain and disability and may
      clinically mimic more common processes affecting the hip and proximal thigh.
      Categories of disease include overuse injuries, traumatic injuries, degenerative
      lesions, and inflammatory lesions. Familiarity with the anatomy and pathologic
      conditions of the fascia lata and its components is important in their
      recognition as a potential source of symptoms. This article illustrates the
      anatomy of this complex fascia through anatomic-pathologic correlation and
      describes the magnetic resonance imaging appearances of the pathologic conditions
      involving it. 

PMID- 24025935
TI  - Multidetector CT angiography for acute gastrointestinal bleeding: technique and
      findings.
AB  - Acute gastrointestinal bleeding is a common reason for emergency department
      admissions and an important cause of morbidity and mortality. Factors that
      complicate its clinical management include patient debility due to comorbidities;
      intermittence of hemorrhage; and multiple sites of simultaneous bleeding. Its
      management, therefore, must be multidisciplinary and include emergency
      physicians, gastroenterologists, and surgeons, as well as radiologists for
      diagnostic imaging and interventional therapy. Upper gastrointestinal tract
      bleeding is usually managed endoscopically, with radiologic intervention reserved
      as an alternative to be used if endoscopic therapy fails. Endoscopy is often less
      successful in the management of acute lower gastrointestinal tract bleeding,
      where colonoscopy may be more effective. The merits of performing bowel cleansing
      before colonoscopy in such cases might be offset by the resultant increase in
      response time and should be weighed carefully against the deficits in
      visualization and diagnostic accuracy that would result from performing
      colonoscopy without bowel preparation. In recent years, multidetector computed
      tomographic (CT) angiography has gained acceptance as a first-line option for the
      diagnosis and management of lower gastrointestinal tract bleeding. In selected
      cases of upper gastrointestinal tract bleeding, CT angiography also provides
      accurate information about the presence or absence of active bleeding, its
      source, and its cause. This information helps shorten the total diagnostic time
      and minimizes or eliminates the need for more expensive and more invasive
      procedures.

PMID- 24025936
TI  - Image-guided intervention in management of complications of portal hypertension:
      more than TIPS for success.
AB  - Management of clinically important sequelae of portal hypertension, such as
      variceal bleeding and ascites, may involve a combination of medical, endoscopic,
      surgical, and interventional approaches and procedures. Although clinically
      significant esophageal and rectal varices are typically visible endoscopically,
      ectopic varices may require multiplanar portal venous phase computed tomography
      or magnetic resonance imaging for diagnosis. A detailed understanding of
      individual vascular anatomy, flow dynamics, and patient-related factors such as
      cardiac and hepatic status is necessary for appropriate treatment selection in
      patients with complicated portal hypertension. The hepatic venous pressure
      gradient is the key indirect measurement of portal venous pressure. Transjugular
      intrahepatic portosystemic shunt (TIPS) placement is regarded as the archetypal
      intervention for treating complicated portal hypertension by reducing portal
      pressure. Various modifications, such as direct portocaval shunt, may be used in
      patients with challenging vascular anatomy. A subset of patients with obstructed
      hepatic venous outflow or portal venous inflow should be considered for
      recanalization. Splenic artery embolization may be considered for reduction of
      portal pressure in selected patients, particularly when hypersplenism or splenic
      vein occlusion is a prominent feature. Gastric and ectopic varices may bleed even
      when the portal pressure is low, and balloon-occluded retrograde transvenous
      obliteration (BRTO) in such patients may lead to equal or improved outcome
      compared with TIPS placement. BRTO is not limited by poor hepatic reserve or
      encephalopathy; however, it does not reduce portal pressure and may aggravate
      esophageal varices. Interventional radiology plays an important role in
      maintaining the patency of surgically created portosystemic shunts, and it
      remains at the forefront of new approaches in shunt design and placement.
      Supplemental material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.335125166/-/DC1. 

PMID- 24025937
TI  - Practice corner: insert character.

PMID- 24025938
TI  - Gestalt of medical images.

PMID- 24025939
TI  - Re: the revised FIGO staging system for uterine malignancies: implications for MR
      imaging.

PMID- 24025940
TI  - Intracranial causes of ophthalmoplegia: the visual reflex pathways.
AB  - The gathering of visual information is a complex process that relies on concerted
      movements of the eyes, and cranial nerves II-VIII are at least partially involved
      in the visual system. The cranial nerves do not function in isolation, however,
      and there are multiple higher-order cortical centers that have input into the
      cranial nerves to coordinate eye movement. Among the functions of the cortical
      reflex pathways are (a) controlling vertical and horizontal gaze in response to
      vestibular input to keep the eyes focused on an object as the head moves through
      space, and (b) controlling rapid, coordinated eye movement to a new visual target
      (saccades). There are also reflex pathways connecting the cranial nerves involved
      in vision that produce consensual blinking of the eyes in response to corneal
      stimulation of one eye and consensual pupillary constriction in response to light
      input on one pupil. A variety of intracranial pathologic conditions, including
      benign and malignant neoplasms, infection, trauma, autoimmune diseases, vascular
      anomalies, degenerative diseases, and inherited-congenital disorders, can disrupt
      the cranial nerves and visual reflex pathways. This disruption can manifest in
      myriad ways-for example, as extraocular muscle paresis, afferent pupillary
      defect, oculosympathetic paresis (Horner syndrome), internuclear ophthalmoplegia,
      dorsal midbrain (Parinaud) syndrome, or loss of the corneal reflex. Knowledge of
      the function and anatomy of the cranial nerves and visual reflex pathways,
      coupled with selection of the proper magnetic resonance pulse sequence, will
      allow the radiologist to order appropriate imaging of the involved cranial nerve
      or visual reflex pathway based on the patient's symptoms and thereby play an
      essential role in establishing the diagnosis and planning appropriate therapy.

PMID- 24025941
TI  - Patterns and signal intensity characteristics of pelvic recurrence of rectal
      cancer at MR imaging.
AB  - Magnetic resonance (MR) imaging is becoming the cross-sectional imaging modality
      of choice for follow-up of patients with previous rectal cancer to diagnose
      pelvic recurrence and plan for surgery. The authors conducted a retrospective
      review of MR imaging examinations performed at their institution for evaluation
      of local recurrence of rectal cancer in 42 patients. Twenty-six patients had
      undergone rectal anastomosis and 16 had undergone abdominoperineal resection. The
      mean interval between initial surgery and recurrence was 2.5 years. Recurrence
      sites were axial (involving the anastomosis) (n = 19); lateral (sidewall) (n =
      6); anterior (prostate or seminal vesicle [n = 2], bladder [n = 4], ureter [n =
      3], vagina or uterus [n = 5]); or posterior (presacral fascia [n = 11], sacrum [n
      = 2]). Other recurrence sites included the pelvic floor (n = 7), sciatic nerve (n
      = 2), obturator nerve (n = 1), perineum (n = 1), abdominal wall (n = 1), or
      adnexa (n = 1). Recurrence was confirmed at surgery or by evidence of tumor
      growth at follow-up imaging. Recurrence patterns, signal intensity
      characteristics, findings of unresectability, potential MR imaging pitfalls, and
      the role of MR imaging versus other modalities in evaluating recurrent rectal
      carcinoma are discussed. Supplemental material available at
      http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg335115170/-/DC1.

PMID- 24025943
TI  - Anatomic comparison of lateral transfer of the long flexors for concomitant
      peroneal tears.
AB  - BACKGROUND: Lateral transfers of the flexor hallucis longus (FHL) or flexor
      digitorum longus (FDL) tendons have been described for treatment of concomitant,
      irreparable peroneal tears. This study evaluated the anatomic benefits and
      constraints of lateral FHL and FDL tendon transfers with regard to available
      tendon length, diameter, and proximity to the posterior neurovascular bundle.
      METHODS: In 9 cadaveric specimens, the FHL and FDL tendons were transected
      through a medial approach distal to the knot of Henry. Each tendon was
      transferred into a lateral incision, passing the FDL tendon both posterior and
      anterior to the tibial neurovascular bundle. The tendons were individually
      secured to the base of the fifth metatarsal with the foot in maximal eversion and
      dorsiflexion. The length of donor tendon available for fixation at the fifth
      metatarsal was measured. After the FDL tendon transfer was secured, the posterior
      neurovascular bundle was examined for signs of compression. RESULTS: Average FHL
      tendon diameter measured 5.1 mm; the FDL measured 4.5 mm. After passage through a
      bone tunnel, an additional 4.9 cm of FHL tendon remained to suture to itself;
      only 0.5 cm remained for the posterior and anterior FDL transfers. Transfer of
      the FHL did not increase muscle bulk within the retrofibular groove. Every FDL
      transfer posterior to the neurovascular bundle produced obvious visual
      compression of the tibial nerve with plantar flexion and inversion of the foot.
      CONCLUSION: Use of the FHL tendon for lateral transfer consistently provided
      sufficient length of tendon for multiple fixation options and a stronger muscle
      for transfer. Fixation options for the FDL were limited due to its shorter
      length. Lateral transfer of the FDL tendon posterior to the neurovascular bundle
      caused visible compression on the tibial nerve with ankle and hindfoot range of
      motion. CLINICAL RELEVANCE: This anatomic study confirmed several advantages for
      the use of the FHL tendon transfer in cases of concomitant peroneal tears.

PMID- 24025944
TI  - JenaValve--transfemoral technology.

PMID- 24025942
TI  - Reduced vesicular storage of catecholamines causes progressive degeneration in
      the locus ceruleus.
AB  - Parkinson's disease (PD) is the most common neurodegenerative motor disease.
      Pathologically, PD is characterized by Lewy body deposition and subsequent death
      of dopamine neurons in the substantia nigra pars compacta. PD also consistently
      features degeneration of the locus ceruleus, the main source of norepinephrine in
      the central nervous system. We have previously reported a mouse model of
      dopaminergic neurodegeneration based on reduced expression of the vesicular
      monoamine transporter (VMAT2 LO). To determine if reduced vesicular storage can
      also cause noradrenergic degeneration, we examined indices of damage to the
      catecholaminergic systems in brain and cardiac tissue of VMAT2 LO mice. At two
      months of age, neurochemical analyses revealed substantial reductions in striatal
      dopamine (94%), cortical dopamine (57%) and norepinephrine (54%), as well as
      cardiac norepinephrine (97%). These losses were accompanied by increased
      conversion of dopamine and norepinephrine to their deaminated metabolites. VMAT2
      LO mice exhibited loss of noradrenergic innervation in the cortex, as determined
      by norepinephrine transporter immunoreactivity and (3)H-nisoxetine binding. Using
      unbiased stereological techniques, we observed progressive degeneration in the
      locus ceruleus that preceded degeneration of the substantia nigra pars compacta.
      In contrast, the ventral tegmental area, which is spared in human PD, remained
      unaffected. The coordinate loss of dopamine and norepinephrine neurons in VMAT2
      LO mice parallels the pattern of neurodegeneration that occurs in human PD, and
      demonstrates that insufficient catecholamine storage can cause spontaneous
      degeneration in susceptible neurons, underscoring cytosolic catecholamine
      catabolism as a determinant of neuronal susceptibility in PD. This article is
      part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative
      Disorders'. 

PMID- 24025945
TI  - St. Jude Medical PorticoTM transapical technology.

PMID- 24025946
TI  - Symetis ACURATE TFTM aortic bioprosthesis.

PMID- 24025947
TI  - Guidelines on valvular heart disease in clinical practice.

PMID- 24025948
TI  - The Colibri heart valve: theory and practice in the achievement of a low-profile,
      pre-mounted, pre-packaged TAVI valve.

PMID- 24025949
TI  - Heart leaflet technology valve.

PMID- 24025950
TI  - Transcatheter mitral valve repair.

PMID- 24025951
TI  - Cerebral protection devices for transcatheter aortic valve implantation: is
      better the enemy of good?
AB  - Transcatheter aortic valve implantation is a widely performed procedure for
      treatment of symptomatic severe aortic stenosis. According to the current
      literature, major stroke has been reported as occurring in 3-6% of patients
      during the first 30 days following valve implantation. Several pathological
      mechanisms may be involved in the development of periprocedural ischaemic stroke
      with the majority being due to thromboembolism and atheroembolism. One approach
      to reduce the incidence of procedural cerebral thromboembolic events is the use
      of cerebral protection devices, either deflecting (Embrella, TriGuard) or
      capturing (Claret, Embol-X) embolic material. We decided to review the current
      evidence on this important issue focusing on the four cerebral protection devices
      currently available. 

PMID- 24025952
TI  - Transcatheter aortic valve implantation: the transfemoral access route is the
      default access.
AB  - Transcatheter aortic valve implantation (TAVI) is a widely accepted alternative
      to surgical aortic valve replacement (SAVR) among non-operable patients or
      selected high-risk patients with degenerative, severe aortic stenosis. TAVI is
      considered less invasive when compared with SAVR; however, there remain
      significant differences between different TAVI access routes. The transfemoral
      approach is considered the least invasive access route, and can be performed as a
      fully percutaneous procedure in a spontaneously breathing patient under local
      anaesthesia and mild sedation only. Moreover, transfemoral TAVI patients are
      typically transferred to coronary care rather than to an intensive care unit
      after the procedure, and benefit from early ambulation and a reduction in overall
      length of hospital stay. Considering these patient-specific and health-economic
      advantages, several TAVI centres follow the least invasive strategy for their
      patients and have implemented the transfemoral access route as the default access
      in their institutions. This article provides an overview on the prerequisites for
      a successful transfemoral TAVI procedure, describes the procedural advantages
      compared to alternative access routes, and highlights differences in clinical
      outcomes. 

PMID- 24025953
TI  - TAVI: transapical--what else?
AB  - Transcatheter aortic valve implantation is a relatively new technique to treat
      elderly and high-risk patients with aortic stenosis using a retrograde
      transfemoral, transsubclavian, transaortic or an antegrade transapical approach.
      TAVI procedures can be divided into two parts: the access to the cardiovascular
      system, and valve positioning and implantation. Regarding access, an antegrade
      transapical approach is intuitively easy to perform and thus the logical
      approach. At present a lateral mini-thoracotomy is required, but for the future
      percutaneous access and closure systems will be available. The transapical
      approach per se offers plenty of advantages as it is easy to perform, is very
      close to the target, antegrade, allows for easy guidewire insertion together with
      simple antegrade valve placement and a very controlled implantation. Despite
      this, in clinical reality many sites use a "transfemoral first" approach to TAVI,
      which is based merely on the belief that this is supposed to be less invasive;
      however, this belief is not substantiated by evidence-based data. In effect, the
      transapical approach offers the lowest access-related complication rates, and
      should therefore be the access of choice for many patients. 

PMID- 24025954
TI  - Transaortic access is the key to success.
AB  - Transcatheter aortic valve implantation (TAVI) using either the Edwards SAPIEN
      Valve or Medtronic CoreValve is a well-established procedure. Although initially
      carried out through transfemoral and transapcial approaches, alternative
      approaches have become popular and have been utilised to optimise the outcomes.
      The transaortic (TAo) approach can be used for both these devices and is carried
      out through the ascending aorta, which can be approached through a partial upper
      J-sternotomy, T-sternotomy or a right anterior thoracotomy. Due to its
      familiarity, this procedure is within the comfort zone of surgeons which reduces
      the learning curve as well as access site-related complications. There are also
      other potential advantages to the TAo approach, which make it versatile and less
      invasive. These advantages, indications, contraindications, surgical technique
      and results will be discussed in this paper. The ongoing ROUTE registry (SAPIEN
      multicentre European TAo registry), prospective CoreValve multicentre European
      registry and data from a pivotal trial for CoreValve in the United States will
      certainly provide robust data in confirming the various advantages seen in
      centres utilising this approach. Dedicated TAo delivery systems, which could also
      be used for the subclavian approach, are on the horizon for the newer devices
      which are currently implanted through other approaches. 

PMID- 24025955
TI  - Subclavian TAVI: more than an alternative access route.
AB  - The standard approach for transcatheter aortic valve implantation (TAVI) is
      through the transfemoral retrograde route, because it is minimally invasive and
      it is feasible under conscious sedation in a totally percutaneous fashion. When
      the transfemoral access is not feasible, the most used approaches are the
      transapical for the balloon-expandable Edwards SAPIEN XT valve, the subclavian
      for the Medtronic self-expandable CoreValve and the transaortic for both
      prostheses. We believe that the subclavian approach should be the first option to
      consider in patients with contraindications to the transfemoral approach, but
      also in those patients who appear at higher risk of vascular complications in the
      case of a feasible but difficult transfemoral approach. Although no direct
      comparison between the subclavian, transaortic and transapical approaches is
      available, in our opinion the subclavian access should be favoured, because of
      its lower invasiveness and its feasibility without general anaesthesia. The
      choice of vascular access should be taken by the Heart Team and should remain
      patient-centred rather than operator-preference driven. 

PMID- 24025956
TI  - Low flow, low gradient severe aortic stenosis: diagnosis, treatment and
      prognosis.
AB  - Low flow, low gradient aortic stenosis is a highly challenging condition in terms
      of diagnosis and therapeutic management. With regard to prognosis and to
      management decisions, it is essential to distinguish those patients with
      preserved systolic left ventricular ejection fraction from patients with impaired
      systolic left ventricular ejection fraction, and in particular those with true
      severe aortic stenosis from patients who have non-significant aortic stenosis
      associated with reduced transvalvular flow for other reasons and who present with
      a functionally small valve area. In addition, measurement errors deserve
      particular consideration in order to avoid a misdiagnosis. Echocardiography,
      including low dose dobutamine stress studies, is the key diagnostic tool.
      Magnetic resonance imaging, invasive assessment of haemodynamics by
      catheterisation and quantification of valve calcification by computed tomography
      calcium scoring can provide additional information that helps to assess aortic
      stenosis severity accurately, predict outcome and guide treatment decisions.
      Percutaneous aortic valve implantation may provide an intervention with lower
      periprocedural risk in this challenging patient subset; however, further studies
      are required to define its exact role in this setting. 

PMID- 24025957
TI  - Antithrombotic and antiplatelet therapy in TAVI patients: a fallow field?
AB  - Guidelines on antithrombotic therapy after TAVI are scarce and no randomised
      evaluation has been performed to demonstrate what the best strategy is.
      Extrapolation from what we know on surgical heart valve replacement is also
      hazardous as the level of evidence is not very high and the situation, the valves
      and the patients are different. Patients undergoing TAVI are fragile and at high
      risk for both bleeding and stroke complications. In addition, the procedure
      itself may contribute to the occurrence of these complications rendering risk
      stratification a key step. Improvement in both periprocedural and post-procedural
      outcome is a major challenge of antithrombotic therapy. The recent release of
      more potent but also safer antithrombotic therapies is a unique opportunity to
      sort out what is the best combination for which patient. Our goal is to review
      the evidence and analyse what are the perspectives in this challenging area. 

PMID- 24025958
TI  - Cost-effectiveness of transcatheter valvular interventions: economic challenges.
AB  - The unsustainable trend of rising healthcare costs necessitates difficult
      allocation decisions by governments, policymakers, and physicians. Consequently,
      recent advances in transcatheter valve therapies require not only clinical
      evaluation, but also careful economic evaluation. Under current indications, each
      year there are nearly 18,000 new candidates for transcatheter aortic valve
      implantation (TAVI) in European countries and an additional 9,200 in North
      America, with an estimated cost of more than $2 billion per year. Nonetheless,
      when compared with standard medical therapy for severe aortic stenosis (AS), TAVI
      leads to gains in life expectancy at an incremental cost that is acceptable by
      most Western standards. On the other hand, for high-risk (but operable) patients
      with severe AS, TAVI provides no proven survival advantage and only a transient
      quality of life benefit compared with surgical aortic valve replacement (SAVR).
      Thus, for these patients, the cost-effectiveness of TAVI compared with SAVR
      hinges on the magnitude and duration of the quality of life benefit as well as
      the relative cost of both procedures. Current data suggest that, for patients who
      are eligible for transfemoral access, TAVI is economically attractive (or even
      economically dominant) compared with high-risk SAVR. However, the cost
      effectiveness of TAVI for patients who are not suitable for a transfemoral
      approach appears to be less favourable. Transcatheter mitral valve repair is in
      an earlier stage of clinical implementation than TAVI. As the evidence for this
      procedure accumulates, more formal economic analysis should be feasible. 

PMID- 24025960
TI  - Severe aortic stenosis and coronary artery disease.
AB  - Coronary artery disease (CAD) and aortic stenosis (AS) share pathophysiological
      mechanisms and risk factors. Moreover, the prevalence of CAD increases among
      elderly patients with severe AS since disease progression is strongly associated
      with age for both CAD and AS. These factors contribute to the frequent
      coexistence of CAD and AS. Patients with concomitant AS and CAD are characterised
      by higher baseline risk profiles with a larger number of comorbidities as
      compared to patients with isolated AS. Therefore, adequate therapeutic strategies
      are crucial for the treatment of these patients. The number of patients
      undergoing concomitant coronary artery bypass grafting (CABG) and surgical aortic
      valve replacement (SAVR) doubled during the last decade. Moreover, the
      development and rapid integration of transcatheter aortic valve implantation
      (TAVI) into clinical practice in western European countries has further extended
      invasive treatment of AS to elderly high-risk patients not considered suitable
      candidates for SAVR, frequently presenting with CAD. The aim of this review
      article is to provide an overview on CAD prevalence, impact on clinical outcomes,
      and treatment strategies in patients with severe AS requiring SAVR or TAVI. 

PMID- 24025959
TI  - Native aortic valve regurgitation: transcatheter therapeutic options.
AB  - Transcatheter aortic valve implantation (TAVI) is an acceptable treatment for
      patients with aortic stenosis but remains contraindicated for patients with
      native aortic valve regurgitation (NAVR). It is well established that patients
      with severe NAVR and symptoms have a poor prognosis if left untreated and that
      they should be offered surgical aortic valve replacement. There are patients with
      NAVR and at high surgical risk for whom conventional surgical aortic valve
      replacement may be unsuitable. Until recently there has been limited experience
      in the treatment of these patients with TAVI but outcomes from isolated case
      reports and small registries are encouraging. Of interest are certain new TAVI
      devices with design features which may make them better suited to the treatment
      of NAVR patients. 

PMID- 24025961
TI  - Aortic stenosis and mitral regurgitation: implications for transcatheter valve
      treatment.
AB  - Moderate or severe mitral regurgitation (MR) is a common finding in patients with
      severe aortic stenosis (AS). The combination may be a relative indication for
      double valve surgery, particularly when MR is severe, degenerative, associated
      with left atrial dilation, chronic atrial fibrillation, or mitral annular
      calcium. However, in patients for whom open surgery is not desirable, TAVI may
      provide a reasonable therapeutic strategy with an expectation in selected
      patients that MR may improve, be better tolerated, or be amenable to staged
      transcatheter mitral interventions. In this paper, we briefly review the surgical
      experience with concomitant AS and MR and discuss the potential implications of
      transcatheter-based heart valve techniques in this patient group. 

PMID- 24025962
TI  - Welcome to PCR London Valves 2013.

PMID- 24025963
TI  - Challenges in transcatheter valve treatment: aortic regurgitation after
      transcatheter aortic valve implantation.
AB  - Paravalvular aortic regurgitation (AR) has a negative impact on the prognosis
      following transcatheter aortic valve implantation (TAVI). As transcatheter heart
      valves (THV) are implanted in a sutureless fashion using oversizing to anchor the
      prosthesis stent frame at the level of the virtual aortic annulus, incomplete
      stent frame expansion due to heavily calcified cusps, suboptimal placement of the
      prosthesis, and/or annulus-prosthesis size mismatch due to malsizing can
      contribute to paravalvular AR with increased mortality in patients with more than
      mild paravalvular AR. Echocardiography is essential to differentiate between
      transvalvular and paravalvular AR and to elucidate further the aetiology of AR
      during the procedure. However, since echocardiographic quantification of AR in
      TAVI patients remains challenging especially in the implantation situation, a
      multimodal approach for the evaluation of AR with use of haemodynamic
      measurements and imaging modalities is imperative to quantify the severity of AR
      precisely immediately after valve implantation. Thus, patients who will benefit
      from corrective measures such as post-dilation or valve-in-valve implantation can
      be identified. In these patients, every measure has to be taken to reduce
      paravalvular aortic regurgitation in order to improve outcome. 

PMID- 24025965
TI  - Transcatheter aortic valve update 2013.
AB  - Cumulative evidence has demonstrated that transcatheter aortic valve implantation
      (TAVI) constitutes an effective treatment option for patients with severe
      symptomatic aortic stenosis and a high operative risk. New valve designs and TAVI
      enabling devices have simplified the procedure, reduced the risk of
      complications, and broadened the applications of this treatment. The global
      adoption of TAVI allows us to appreciate the advantages, potentialities and
      caveats of the technology, identify patients who would benefit from TAVI and
      stratify more accurately the risk of complications. The focus of this article is
      to discuss the advances in this field, present the current evidence, and
      highlight the developments and strategies proposed to address the limitations of
      TAVI treatment. 

PMID- 24025964
TI  - Failing surgical bioprosthesis in aortic and mitral position.
AB  - Bioprosthetic heart valves are preferentially selected over mechanical prostheses
      in the majority of patients undergoing valve replacement surgery. These
      bioprostheses are prone to structural degeneration, and hence an increasing
      number of patients are presenting with bioprosthetic failure requiring redo
      surgery. In selected high-risk cases, successful implantation of a transcatheter
      aortic valve (TAV) within the failing bioprosthetic surgical aortic valve (SAV)
      or mitral valve (SMV) has been performed. Herein, we summarise the available
      evidence, describe the technical challenges, and highlight important procedural
      considerations for these innovative interventions. 

PMID- 24025966
TI  - Sharing experience: the evolving treatment of valvular heart disease in 2013.

PMID- 24025967
TI  - The Helio transcatheter aortic dock for patients with aortic regurgitation.

PMID- 24025968
TI  - Medtronic CoreValve Evolut R with EnVeo R.

PMID- 24025969
TI  - Medtronic EngagerTM bioprosthesis for transapical transcatheter aortic valve
      implantation.

PMID- 24025970
TI  - Annihilation dynamics of stringlike topological defects in a nematic lyotropic
      liquid crystal.
AB  - Topological defects can appear whenever there is some type of ordering. Its
      ubiquity in nature has been the subject of several studies, from early Universe
      to condensed matter. In this work, we investigated the annihilation dynamics of
      defects and antidefects in a lyotropic nematic liquid crystal (ternary mixture of
      potassium laurate, decanol and deionized-destillated water) using the polarized
      optical light microscopy technique. We analyzed Schlieren textures with
      topological defects produced due to a symmetry breaking in the transition of the
      isotropic to nematic calamitic phase after a temperature quench. As result, we
      obtained for the distance D between two annihilating defects (defect-antidefect
      pair), as a function of time t remaining for the annihilation, the scaling law D
      ? t(alpha), with alpha = 0.390 and standard deviation sigma = 0.085. Our findings
      go in the direction to extend experimental results related to dynamics of defects
      in liquid crystals since only thermotropic and polymerics ones had been
      investigated. In addition, our results are in good quantitative agreement with
      previous investigations on the subject. 

PMID- 24025972
TI  - HER-2/neu mediates oncogenic transformation via altered CREB expression and
      function.
AB  - The cyclic (c)AMP responsive element binding protein (CREB) plays a key role in
      many cellular processes, including differentiation, proliferation, and signal
      transduction. Furthermore, CREB overexpression was found in tumors of distinct
      origin and evidence suggests an association with tumorigenicity. To establish a
      mechanistic link between HER-2/neu-mediated transformation and CREB protein
      expression and function, in vitro models of HER-2/neu-overexpressing and HER
      2/neu-negative/silenced counterparts as well as human mammary carcinoma lesions
      with defined HER-2/neu status were used. HER-2/neu overexpression resulted in the
      induction and activation of CREB protein in vitro and in vivo, whereas short
      hairpin RNA (shRNA)-mediated inhibition of HER-2/neu correlated with
      downregulated CREB activity. CREB activation in HER-2/neu-transformed cells
      enhanced distinct signal transduction pathways, whereas their inhibition
      negatively interfered with CREB expression and/or activation. CREB downregulation
      in HER-2/neu-transformed cells by shRNA and by the inhibitors KG-501 and
      lapatinib caused morphologic changes, reduced cell proliferation with G0-G1 cell
      cycle arrest, which was rescued by CREB expression. This was accompanied by
      reduced cell migration, wound healing, an increased fibronectin adherence,
      invasion, and matrix metalloproteinase expression. In vivo shCREB-HER-2/neu(+)
      cells, but not control cells, exerted a significantly decreased tumorgenicity
      that was associated with decreased proliferative capacity, enhanced apoptosis,
      and increased frequency of T lymphocytes in peripheral blood mononuclear cells.
      Thus, CREB plays an important role in the HER-2/neu-mediated transformation by
      altering in vitro and in vivo growth characteristics. IMPLICATIONS: These data
      suggest that CREB affects tumor immunogenicity and is a potential target for
      cancer therapy.

PMID- 24025971
TI  - CXCR4, but not CXCR7, discriminates metastatic behavior in non-small cell lung
      cancer cells.
AB  - Chemokines have been implicated as key contributors of non-small cell lung cancer
      (NSCLC) metastasis. However, the role of CXCR7, a recently discovered receptor
      for CXCL12 ligand, in the pathogenesis of NSCLC is unknown. To define the
      relative contribution of chemokine receptors to migration and metastasis, we
      generated human lung A549 and H157 cell lines with stable knockdown of CXCR4,
      CXCR7, or both. Cancer cells exhibited chemotaxis to CXCL12 that was enhanced
      under hypoxic conditions, associated with a parallel induction of CXCR4, but not
      CXCR7. Interestingly, neither knockdown cell line differed in the rate of
      proliferation, apoptosis, or cell adherence; however, in both cell lines, CXCL12
      induced migration was abolished when CXCR4 signaling was abrogated. In contrast,
      inhibition of CXCR7 signaling did not alter cellular migration to CXCL12. In an
      in vivo heterotropic xenograft model using A549 cells, expression of CXCR4, but
      not CXCR7, on cancer cells was necessary for the development of metastases. In
      addition, cancer cells knocked down for CXCR4 (or both CXCR4 and CXCR7) produced
      larger and more vascular tumors as compared with wild-type or CXCR7 knockdown
      tumors, an effect that was attributable to cancer cell-derived CXCR4 out
      competing endothelial cells for available CXCL12 in the tumor microenvironment.
      These results indicate that CXCR4, not CXCR7, expression engages CXCL12 to
      mediate NSCLC metastatic behavior. IMPLICATIONS: Targeting CXCR4-mediated
      migration and metastasis may be a viable therapeutic option in NSCLC.

PMID- 24025973
TI  - Size matters: implications of the loss of large individuals for ecosystem
      function.
AB  - Size is a fundamental organismal trait and an important driver of ecosystem
      functions. Although large individuals may dominate some functions and provide
      important habitat structuring effects, intra-specific body size effects are
      rarely investigated in the context of BEF relationships. We used an in situ
      density manipulation experiment to explore the contribution of large, deep
      burrowing bivalves to oxygen and nutrient fluxes across the sediment-water
      interface. By manipulating bivalve size structure through the removal of large
      individuals, we held species identity constant, but altered the trait
      characteristics of the community. The number of large bivalves was the best
      predictor of ecosystem functioning. Our results highlight that (a) accounting for
      body size provides important insights into the mechanisms underpinning
      biodiversity effects on ecosystem function, and (b) if local disturbances are
      recurrent, preventing individuals from reaching large sizes, the contribution of
      large adults may be lost, with largely unknown implications for ecosystem
      functionality. 

PMID- 24025974
TI  - Impact of lamivudine-resistance mutations on entecavir treatment outcome in
      hepatitis B.
AB  - BACKGROUND AND OBJECTIVE: Entecavir (ETV) is a potent inhibitor of viral
      replication in nucleos(t)ide analog (NA)-naive chronic hepatitis B patients with
      a very low rate of resistance (<=1.2%) over 5 years. The aim of this study was to
      assess the efficacy of ETV treatment in routine clinical practice and to
      investigate whether persistence of residual viral replication was the result of
      the emergence and selection of drug-resistant mutants. PATIENTS AND METHODS:
      Chronic hepatitis B patients treated with ETV were consecutively recruited from
      the Department of Hepatology, Hospices Civils de Lyon, France, and were monitored
      regularly within their routine clinical follow-up. Virological, biochemical,
      clinical, and tolerance findings were assessed prospectively. RESULTS: A total of
      79 patients were studied, of whom 58% received ETV as a first-line therapy.
      During ETV therapy (median follow-up 42 months), hepatitis B virus (HBV) DNA
      became undetectable in 95% of patients. Time to HBV DNA undetectability was
      significantly shorter in patients with an HBV DNA level less than 4 log10 IU/ml
      at baseline and in HBeAg-negative patients. Moreover, time to undetectability was
      significantly shorter in patients with no or only one lamivudine-resistance
      (LAMr) mutation than in patients with two or more LAMr mutations (P=0.050). No
      patient had renal-function impairment during ETV therapy. CONCLUSION: In routine
      clinical practice, ETV is effective in both NA-naive and NA-experienced patients,
      except in patients with HBV strains harboring at least two LAMr mutations. The
      analysis of viral genome sequence at the time of treatment adaptation could prove
      useful to personalize antiviral therapy in patients failing a previous line of
      treatment.

PMID- 24025975
TI  - Severe exacerbation of Crohn's disease during sunitinib treatment.
AB  - Sunitinib is a multiple tyrosine kinase inhibitor of the vascular endothelial
      growth factor and platelet-derived growth factor pathway and inhibits
      angiogenesis, cell proliferation, and tumor cell invasion, and stimulates
      apoptosis. Treatment with sunitinib in first-line metastatic renal cell carcinoma
      improves progression-free survival and overall survival compared with interferon
      alpha. Crohn's disease is characterized by chronic immune-mediated intestinal
      inflammation. Although the exact pathogenesis of Crohn's disease remains unknown,
      the involvement of angiogenesis is acknowledged. It is unknown whether sunitinib
      interferes with the natural course of Crohn's disease. We describe a patient with
      metastatic renal cell carcinoma and a history of Crohn's disease who was treated
      with sunitinib and developed a severe exacerbation of Crohn's disease. After
      rechallenge with sunitinib, a second exacerbation occurred. We therefore conclude
      that angiogenesis inhibitors should be administered with care in patients with a
      history of Crohn's disease. 

PMID- 24025976
TI  - Role of C-reactive protein in response-guided therapy of pyogenic liver abscess.
AB  - BACKGROUND: Protocols for antibiotic treatment of pyogenic liver abscess (PLA)
      are usually based on clinicians' own experience without any validation. Our study
      was to evaluate the clinical implication of C-reactive protein (CRP) in
      predicting treatment outcome and adequacy of antibiotic therapy of PLA. PATIENTS
      AND METHODS: Patients with PLA in whom white blood cell (WBC) count, erythrocyte
      sedimentation rate (ESR), and CRP were checked regularly during the clinical
      course were included. The prolife of CRP during the clinical course was compared
      with that of ESR and WBC. The usefulness of CRP in predicting the chance of
      recovery and adequacy of antibiotic therapy was examined. RESULTS: From 2000 to
      2011, 109 patients with PLA underwent regular monitoring of WBC, ESR, and CRP.
      Except for ESR, both WBC and CRP showed an initial rapid reduction in first 3
      weeks, followed by a relatively slow decrease. From week 3 to week 6, the CRP
      ratio (relative to CRP at week 1) of patients with and without adverse events
      (i.e. including mortality) was compared; a significant difference was found at
      week 3 (P=0.001), week 4 (P=0.004), week 5 (P=0.011), and week 6 (P=0.018),
      whereas no statistically significant difference was found in the WBC ratio over
      the same period. By week 3, a CRP ratio of 0.423 or less was a marker of good
      outcome (sensitivity 0.846; specificity 0.667) and was also a marker of adequacy
      of antibiotic therapy of 5 weeks or less (sensitivity 0.786; specificity 0.714)
      if the ratio was 0.278 or less. CONCLUSION: Weekly CRP measurement was useful in
      the identification of patients with PLA with good outcome and adequacy of
      antibiotic therapy of 5 weeks or less.

PMID- 24025977
TI  - In patients with liver cirrhosis, proinflammatory interleukins correlate with
      health-related quality of life irrespective of minimal hepatic encephalopathy.
AB  - BACKGROUND: Liver cirrhosis is associated with latent systemic inflammatory
      response syndrome as evidenced by elevated levels of proinflammatory cytokines.
      It has been proposed that inflammatory mediators play a role in the pathogenesis
      of minimal and overt hepatic encephalopathy (HE); hence, they may also have an
      effect on health-related quality of life (HRQL). The aim of this study was to
      investigate the relationship between serum levels of interleukin-1beta (IL
      1beta), IL-6, and IL-18 and the occurrence of minimal HE and HRQL. METHODS: Forty
      two consecutive patients with liver cirrhosis were prospectively enrolled to the
      study. Minimal HE was detected by the Psychometric Hepatic Encephalopathy Score
      (PHES) and critical flicker frequency. HRQL was assessed with Chronic Liver
      Disease Questionnaire and 36-Item Short Form Health Survey (SF-36)
      questionnaires. The interleukins studied were determined using colorimetric
      sandwich enzyme-linked immunosorbent assay. RESULTS: Serum levels of interleukins
      correlated with liver dysfunction, but did not discriminate patients with minimal
      HE from those with overt or absent HE. IL-1beta and IL-6 showed significant
      correlations with PHES, but showed no relationship with critical flicker
      frequency. Serum IL-6 and IL-18 correlated with both physical-related general
      health and mental component summary evaluated by the SF-36 questionnaire.
      CONCLUSION: This study shows that chronic inflammation plays a role in impaired
      HRQL in patients with cirrhosis irrespective of minimal HE.

PMID- 24025978
TI  - Perceptions of gastroenterologists and patients regarding irritable bowel
      syndrome and inflammatory bowel disease.
AB  - OBJECTIVE: To compare perceptions of patients and gastroenterologists regarding
      irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). METHODS: The
      Illness Perception Questionnaire-Revised was sent to 150 randomly selected
      hospital-based and community-based gastroenterologists nationwide. Participants
      were instructed to refer their responses to either IBS or IBD. Patients were
      recruited during a regular visit to the Gastroenterology Department of a tertiary
      medical center and completed the same questionnaire. Findings were analyzed
      according to illness and group. RESULTS: Questionnaires were returned by 55
      physicians (29 referred to IBS, 26 to IBD) and 58 patients. Physicians and
      patients stated that IBD has more severe consequences and benefits more from
      medical treatment (P<0.05), and that patient coherence is higher for IBD than IBS
      (P<0.05). Physicians stated that psychological attributes and accidents/injuries
      play a greater causative role in IBS than in IBD (P<0.01 and P<0.05,
      respectively). Conversely, patients found no such difference. More patients than
      physicians attributed both illnesses to risk factors (P=0.07). Both groups
      believed that the immune system is a more important causative factor in IBD than
      IBS (P<0.01). CONCLUSION: The different views of gastroenterologists and patients
      in terms of the involvement of psychological attributes, risk factors, and
      accidents/injuries in IBD and IBS could affect the patient-health provider
      relationship and adversely impact treatment outcome.

PMID- 24025979
TI  - Nocturnal and daytime esophageal acid exposure in normal-weight, overweight, and
      obese patients with reflux symptoms.
AB  - OBJECTIVES: This study aimed to investigate the association between BMI and
      esophageal acid exposure in a cohort of patients referred for esophageal pH
      monitoring. The contributing roles of hiatal hernia, lower esophageal sphincter
      (LES) pressure, and intragastric pressure (IGP) were investigated, with an
      emphasis on reflux in the supine position. METHODS: Esophageal manometry and 24-h
      pH-metry results were extracted from a prospectively collected database, and
      supplemental data (body mass, endoscopy results) from patient files. RESULTS: In
      total, 245 patients (mean age 52.2+/-14 years, 54% men) were included in this
      study. In the normal-weight subgroup (n=87), the median acid exposure time was
      1.1% [0-8.1] in the supine position (with interquartile range 25-75%) and 7.7%
      [2.5-14.8] in the upright position; the total acid exposure time was 7.4% [2.7
      11.7]/24 h. In the overweight subgroup (n=104), the median acid exposure time was
      4.9% [0.3-13.3] in the supine position and 11.1% [5.4-16.9] in the upright
      position; the total acid exposure time was 8.9% [4.7-15.8]/24 h. In the obesity
      subgroup (n=54), the median acid exposure time was 4.1% [0.7-14.3] in the supine
      position and 10.5% [5-17.5] in the upright position; the total acid exposure time
      was 8.3% [5.3-14.7]/24 h. Supine acid exposure was significantly higher in
      overweight and obese patients than in normal-weight patients (both P=0.02). In
      overweight patients, a hiatal hernia was predictive of supine and total acid
      exposure, as was a decreasing LES pressure in both the supine and the upright
      position. In obese patients, increased IGP contributed toward an increased total
      acid exposure. Although an association between increasing BMI and acid exposure
      was observed, BMI was not independently predictive. CONCLUSION: Overweight and
      obesity is associated with increased reflux, especially in the supine position.
      The most important factors that contribute toward reflux are the presence of a
      hiatal hernia and a lower LES pressure in overweight patients and an increased
      IGP in obese patients.

PMID- 24025980
TI  - High red blood cell distribution width is closely associated with nonalcoholic
      fatty liver disease.
AB  - BACKGROUND: The red blood cell distribution width (RDW) has been reported to be a
      risk marker of morbidity and mortality for cardiovascular diseases in various
      study populations. Nonalcoholic fatty liver disease (NAFLD) is also a risk factor
      for cardiovascular diseases. However, the relationship between RDW and NAFLD is
      less certain. PATIENTS AND METHODS: RDW was determined using a Coulter counter
      together with the hemoglobin level in 1637 normal control individuals and 619
      NAFLD patients who were consecutively referred by general practitioners for
      routine medical check-up. The total plasma cholesterol, plasma triglyceride, and
      fasting glucose were determined using a multichannel analyzer, and BMI, systolic
      blood pressure (SBP), diastolic blood pressure (DBP), and the incidence of
      hypertension and coronary artery disease were measured using statistical
      analysis. RESULTS: Patients with NAFLD had a higher RDW, BMI, waist to hip ratio,
      SBP and DBP, fasting glucose, triglycerides, and hypertension incidence (P<0.01),
      and were also younger (P<0.01). NAFLD was considered as a dependent variable,
      whereas age, sex, BMI, waist to hip ratio, RDW, hemoglobin, SBP and DBP, fasting
      glucose, total cholesterol, triglyceride, and hypertension were considered as
      covariate variables. We found that age (beta=-0.031, P<0.01), BMI (beta=0.265,
      P<0.01), waist to hip ratio (beta=6.166, P<0.01), RDW (beta=0.154, P<0.01),
      fasting plasma glucose (beta=0.301, P<0.01), and triglyceride (beta=0.222,
      P<0.01) were significantly associated with the risk for NAFLD, analyzed by binary
      logistic regression analysis. CONCLUSION: Patients with NAFLD were more likely to
      have high levels of RDW. Moreover, NAFLD was associated with age, BMI, RDW,
      fasting plasma glucose, and triglyceride. If confirmed in future follow-up
      studies, this association might provide a rationale to introduce the easy,
      inexpensive RDW in algorithms for NAFLD risk prediction.

PMID- 24025981
TI  - A protective layer approach to solvatochromic sensors.
AB  - As they have been designed to undergo colorimetric changes that are dependent on
      the polarity of solvents, the majority of conventional solvatochromic molecule
      based sensor systems inevitably display broad overlaps in their absorption and
      emission bands. As a result, colorimetric differentiation of solvents of similar
      polarity has been extremely difficult. Here we present a tailor-made colorimetric
      and fluorescence turn-on type solvatochromic sensor that enables facile
      identification of a specific solvent. The sensor system displays a colorimetric
      transition only when a thin protective layer, which protects the solvatochromic
      materials, is destroyed or disrupted by a specific solvent. The versatility of
      the strategy is demonstrated by designing a sensor that differentiates chloroform
      and dichloromethane colorimetrically and one that performs sequence selective
      colorimetric sensing. In addition, the approach is employed to construct a
      solvatochromic molecular AND logic gate. The new strategy could open new avenues
      for the development of novel solvatochromic sensors. 

PMID- 24025982
TI  - Ground-state fidelity of the spin-1 Heisenberg chain with single ion anisotropy:
      quantum renormalization group and exact diagonalization approaches.
AB  - We study the phase diagram of the anisotropic spin-1 Heisenberg chain with single
      ion anisotropy (D) using a ground-state fidelity approach. The ground-state
      fidelity and its corresponding susceptibility are calculated within the quantum
      renormalization group scheme where we obtained the renormalization of fidelity
      preventing calculation of the ground state. Using this approach, the phase
      boundaries between the antiferromagnetic Neel, Haldane and large-D phases are
      obtained for the whole phase diagram, which justifies the application of quantum
      renormalization group to trace the symmetry-protected topological phases. In
      addition, we present numerical exact diagonalization (Lanczos) results in which
      we employ a recently introduced non-local order parameter to locate the
      transition from Haldane to large-D phase accurately. 

PMID- 24025983
TI  - Single-dose pharmacokinetics of the HCV polymerase inhibitor mericitabine in
      healthy Caucasian and Japanese subjects.
AB  - To investigate the pharmacokinetics of mericitabine in healthy Caucasian and
      Japanese subjects, healthy Caucasian (n = 32) and Japanese (n = 32) subjects were
      randomized to receive single 500, 1,000, or 2,000 mg doses of mericitabine or a
      placebo, after which plasma and urine samples were collected for 72 h.
      Mericitabine (prodrug), RO4995855 (parent), and RO5012433 (uridine metabolite)
      concentrations were quantified by tandem mass spectrometry. Pharmacokinetics were
      estimated by non-compartmental methods, and pharmacokinetic parameters of
      RO4995855 were normalized by body weight. Exposure to RO4995855 was similar in
      both populations after administration of mericitabine 500, 1,000, and 2,000 mg.
      Mean AUCinf of RO4995855 increased in a dose-proportional manner from 28.8 to
      52.3, and 113.0 ug.h/mL in Caucasian subjects, and from 32.5 to 57.1 and 119
      ug.h/mL in Japanese subjects. A linear relationship was observed between the
      weight-adjusted dose of mericitabine and Cmax (r(2) = 0.83 and 0.80) and AUC
      (r(2) = 0.94 and 0.74) for RO4995855 in Caucasian and Japanese subjects,
      respectively. Mean half-life and renal clearance of RO4995855 were similar and
      independent of dose in both populations. The results support the use of the same
      dosing regimens in Caucasian and Asian subjects.

PMID- 24025984
TI  - Variability of bioavailability and intestinal absorption mechanisms of
      metoprolol.
AB  - We previously reported that aging and/or cytochrome P450 2D6 polymorphism are
      responsible for the interindividual variability in the systemic clearance (CL)
      and bioavailability (F) of metoprolol. The aim of the present study was to
      evaluate the residual variability of F of metoprolol in routinely treated
      Japanese patients and to investigate the intestinal absorption mechanism of the
      drug using human intestinal epithelial LS180 cells. We first re-analyzed the
      blood concentration data for metoprolol in 34 Japanese patients using a nonlinear
      mixed effects model. The oral clearance (CL/F) of metoprolol was positively
      correlated with the apparent volume of distribution (V/F), suggesting the
      residual variability of F. The uptake of metoprolol into LS180 cells was
      significantly decreased by the acidification of extracellular medium pH, and was
      dependent on temperature and intracellular pH. Furthermore, the cellular uptake
      of metoprolol was saturable, and was significantly decreased in the presence of
      hydrophobic cationic drugs such as diphenhydramine, procainamide, bisoprolol, and
      quinidine. These findings indicate that residual variability of F is one of the
      causes of the interindividual pharmacokinetic variability of metoprolol, and that
      the interindividual variability of not only presystemic first-pass metabolism,
      but also intestinal absorption, may be responsible for the variable F of the
      drug.

PMID- 24025985
TI  - Identification and characterization of human UDP-glucuronosyltransferases
      responsible for the glucuronidation of fraxetin.
AB  - Fraxetin, a major constituent of the traditional medicine plant Fraxinus
      rhynchophylla Hance (Oleaceae), has been found to possess multiple bioactivities.
      However, the metabolic pathway(s) of fraxetin in human tissues has not been
      reported yet. This study aimed to characterize the glucuronidation pathway(s) of
      fraxetin in human tissues. Fraxetin could be metabolized to two glucuronides in
      human liver microsomes (HLMs). These two glucuronides were biosynthesized and
      characterized as 7-O-glucuronide (7-O-G) and 8-O-glucuronide (8-O-G). UGT1A1, 
      1A6, -1A7, -1A8, -1A9 and -1A10 participated in the formation of 7-O-G, while the
      formation of 8-O-G was catalyzed selectively by UGT1A6 and UGT1A9. UGT1A9 showed
      the highest catalytic activities in the formation of 7-O-G and 8-O-G. Both
      kinetic characterization and inhibition assays demonstrated that UGT1A9 played
      important roles in fraxetin glucuronidations in HLMs, especially in the formation
      of the major metabolite 8-O-G. Furthermore, the intrinsic clearance of fraxetin
      in both human liver microsomes and UGT1A9 was greater than that of 7,8
      dihydroxylcoumarin, revealing that the addition of a C-6 methoxy group led to the
      higher metabolic clearance. In summary, the glucuronidation pathways of fraxetin
      in human liver microsomes were well-characterized, and UGT1A9 was the major
      isoform responsible for the glucuronidations of fraxetin.

PMID- 24025986
TI  - A common variant of organic anion transporter 4 (OAT4/SLC22A11) gene is
      associated with renal underexcretion type gout.
AB  - Gout, a common disease, is a consequence of hyperuricemia, and increases the
      risks of hypertension, cardiovascular diseases, cerebrovascular diseases and
      renal failure. Gout can be classified into 3 types: the renal underexcretion
      (RUE) type, renal overload type and combined type. RUE type is a major type of
      gout; however, its genetic causes are still unclear. Since human organic anion
      transporter 4 (OAT4/SLC22A11) is expressed in the kidney and mediates urate
      transport, we investigated the effects of a common variant of OAT4/SLC22A11 on
      the susceptibility to gout. Five hundred and forty-five Japanese male gout cases
      and 1,115 male individuals as a control group were genotyped with rs17300741, a
      single nucleotide polymorphism in the OAT4/SLC22A11 gene. The association
      analysis of rs17300741 showed no significant association for all gout cases;
      however, there was a slight but significant association for RUE type gout cases
      (p = 0.049). These results also suggest that OAT4 contributes to urate transport
      at the apical membrane of renal proximal tubule cells in humans. Our findings
      make it clear for the first time that a common variant of OAT4/SLC22A11 is
      associated with RUE type gout, a major gout subtype.

PMID- 24025987
TI  - Glucuronidation and subsequent biliary excretion of mycophenolic acid in rat
      sandwich-cultured hepatocytes.
AB  - Rat sandwich-cultured hepatocytes (SCH) were used to correlate the in vitro
      hepatic disposition of mycophenolic acid (MPA) with published in vivo data, as
      well as mechanistic studies on drug-drug interaction. The major metabolite of MPA
      in SCH was 7-O-glucuronide (MPAG) followed by acyl-glucuronide (AcMPAG). MPAG and
      AcMPAG, but not MPA, showed significant in vitro biliary excretion with biliary
      excretion indexes (BEI) of 40% for MPAG and 45% for AcMPAG. While these BEIs were
      similar, the biliary excretion amount (BEA) of MPAG (120 pmol/mg protein) was
      orders of magnitude higher than that of AcMPAG (0.34 pmol/mg protein). Since MPAG
      is the major metabolite in in vivo bile, we propose that BEA is a better
      qualifier of biliary excretion. Quercetin inhibited MPAG and AcMPAG production,
      while chrysin inhibited only MPAG production, showing that chrysin is not a pan
      glucuronidation inhibitor. Cyclosporin A (CysA) reduced the BEI of MPAG and
      increased intracellular MPA accumulation without changing MPAG amounts. These
      results suggest that CysA causes inhibition of biliary excretion of MPAG, as well
      as a mixed inhibition of glucuronidation of MPA and sinusoidal efflux of
      MPA/MPAG. In conclusion, the present study demonstrates a good agreement of
      hepatic MPA disposition between SCH and in vivo rats.

PMID- 24025988
TI  - Effects of peritoneal dialysis on pharmacotherapy: a deductive pharmacokinetic
      model approach to predict drug concentration profiles in plasma and peritoneal
      fluid.
AB  - The aim of this study was to present a deductive compartment pharmacokinetic (PK)
      model to predict the concentration profiles of drugs in plasma and peritoneal
      fluid in peritoneal dialysis (PD) rats. PK parameters of model drugs in normal
      and experimentally induced acute renal failure (ARF) rats not undergoing PD were
      obtained inductively in a common regression manner with a two-compartment model.
      In PD normal and ARF rats, PK parameters relating to the transfer of drugs to the
      peritoneal dialysate and the progress of renal failure were deductively modified
      to simulate the drug concentration-time profiles in plasma and in the peritoneal
      fluid in PD rats. The deductively introduced modifiers were the volume of
      distribution in the peripheral compartment, plasma protein binding, and solvent
      movement factor to the peritoneal fluid. Predicted profiles of tolbutamide,
      propranolol and cefazolin in PD normal and ARF rats were compared with the
      corresponding observed data. This minimal deductive approach yielded satisfactory
      accuracy in the prediction of both the plasma and peritoneal fluid concentrations
      of tolbutamide and propranolol.

PMID- 24025989
TI  - No increase of local recurrence rate in breast cancer patients treated with skin
      sparing mastectomy followed by immediate breast reconstruction.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence of local
      recurrence after SSM with IBR and to determine whether complications lead to
      postponement of adjuvant therapy. METHOD: Patients that underwent IBR after SSM
      between 2004 and 2011 were included. RESULTS: A total of 157 reconstruction
      procedures were performed in 147 patients for invasive breast cancer (n = 117)
      and ductal carcinoma in situ (n = 40). The median follow-up was 39 months [range
      6-97]. Estimated 5-year local recurrence rate was 2.9% (95% CI 0.1-5.7). The
      median time to start adjuvant therapy was 27.5 days [range 19-92] in 18 patients
      with complications, and 23.5 days [range 8-54] in 46 patients without
      complications (p = 0.025). CONCLUSION: In our single-institution cohort, IBR
      after SSM carried an acceptable local recurrence rate. Complications caused a
      delay of adjuvant treatment but this was within guidelines and therefore not
      clinically relevant.

PMID- 24025990
TI  - Pd-Catalyzed stereospecific allyl-aryl coupling of allylic alcohols with
      arylboronic acids.
AB  - An efficient method for Pd-catalyzed stereospecific allyl-aryl coupling of
      allylic alcohols with arylboronic acids has been described. The reactions
      proceeded smoothly in the presence of Pd2(dba)3.CHCl3 and racemic BINAP under
      mild and neutral conditions, affording allyl-aryl coupling products in moderate
      to high yields with excellent stereospecificities. 

PMID- 24025991
TI  - Free-decay and resonant methods for investigating the fundamental limit of
      superhydrophobicity.
AB  - The recently demonstrated extremely water-repellent surfaces with contact angles
      close to 180 degrees  with nearly zero hysteresis approach the fundamental limit
      of non-wetting. The measurement of the small but non-zero energy dissipation of a
      droplet moving on such a surface is not feasible with the contemporary methods,
      although it would be needed for optimized technological applications related to
      dirt repellency, microfluidics and functional surfaces. Here we show that
      magnetically controlled freely decaying and resonant oscillations of water
      droplets doped with superparamagnetic nanoparticles allow quantification of the
      energy dissipation as a function of normal force. Two dissipative forces are
      identified at a precision of ~ 10 nN, one related to contact angle hysteresis
      near the three-phase contact line and the other to viscous dissipation near the
      droplet-solid interface. The method is adaptable to common optical goniometers
      and facilitates systematic and quantitative investigations of dynamical
      superhydrophobicity, defects and inhomogeneities on extremely superhydrophobic
      surfaces. 

PMID- 24025992
TI  - Electron correlation and relativistic effects in the secondary NMR isotope shifts
      of CSe2.
AB  - Secondary isotope effects on nuclear shielding provide an experimentally well
      defined reference point of quantum-chemical methodology. We carry out a quantum
      mechanical treatment of thermal rovibrational motion in the linear CSe2 molecule
      and combine it with relativistic modeling of (77)Se and (13)C nuclear magnetic
      shieldings. The effects of electron correlation are studied at nonrelativistic
      (NR) ab initio and both NR and relativistic density functional theory (DFT)
      levels. Fully relativistic 4-component Dirac-DFT (D-DFT) as well as Breit-Pauli
      perturbation theory (BPPT) are used to produce the relativistic shielding
      surfaces. Quantitative agreement with the experimental secondary isotope effects
      can be obtained by a piecewise combination of a high-level ab initio NR shielding
      surface with the more approximate, albeit reasonable-quality relativistic
      corrections by DFT at either Dirac or BPPT levels of theory, when operating at
      the basis-set limit. Using a high-quality potential energy surface is also
      crucial, which further underlines the highly demanding nature of modeling of the
      isotope shifts. 

PMID- 24025993
TI  - On the ubiquitous presence of fractals and fractal concepts in pharmaceutical
      sciences: a review.
AB  - Fractals have been very successful in quantifying nature's geometrical
      complexity, and have captured the imagination of scientific community. The
      development of fractal dimension and its applications have produced significant
      results across a wide variety of biomedical applications. This review deals with
      the application of fractals in pharmaceutical sciences and attempts to account
      the most important developments in the fields of pharmaceutical technology,
      especially of advanced Drug Delivery nano Systems and of biopharmaceutics and
      pharmacokinetics. Additionally, fractal kinetics, which has been applied to
      enzyme kinetics, drug metabolism and absorption, pharmacokinetics and
      pharmacodynamics are presented. This review also considers the potential benefits
      of using fractal analysis along with considerations of nonlinearity, scaling, and
      chaos as calibration tools to obtain information and more realistic description
      on different parts of pharmaceutical sciences. As a conclusion, the purpose of
      the present work is to highlight the presence of fractal geometry in almost all
      fields of pharmaceutical research. 

PMID- 24025994
TI  - In vivo reprogramming in inflammatory bowel disease.
AB  - The direct reprogramming of somatic cells has immense implications in various
      areas of medicine. Although remarkable progress has been made in developing novel
      reprogramming methods, the efficiency and fidelity of reprogramming still need to
      be improved. Inflammatory bowel disease (IBD) involves chronic inflammatory
      diseases of the gastrointestinal tract with a complex etiology caused by various
      genetic, immunological and environmental factors. Recently, the role of stem
      cells has been proposed in pathogenesis and therapy of IBD. However, the
      efficiency and the safety of the stem cell treatments depend on the origin of the
      stem cell and the administration method. We hypothesize that the reprogramming of
      the intestinal cells into a pluripotent state is of huge importance for IBD
      therapy and prevention. The vectors carrying reprogramming genes encoding
      pluripotency factors can be transferred to the damaged tissue, in this case the
      intestine, by means of invasive bacterial vectors able to colonize colon mucosa.
      Reconstruction of tissues in vivo might avoid problems encountered in tissue
      rebuilding in vitro because of lack of appropriate scaffolds and
      microenvironments. Herein we present a review of recent literature and a
      perspective of in vivo reprogramming in IBD using bacterial vectors and analyze
      the rationale for such approach. 

PMID- 24025995
TI  - Searching for bumps and ellipses on the ground and in the sky: no advantage for
      the ground plane.
AB  - A staple of modern theories of vision is that the visual system has evolved to
      perceive cues containing the most predictive information about the layout of the
      environment. This entails the prediction that - other things being equal - visual
      performance in a familiar setting should be superior to performance in an
      unfamiliar one. Visual performance should therefore be better on the familiar
      ground plane compared to an implied sky or wall plane. We tested this comparing
      visual search for stimuli presented in an implied ground plane with search on a
      180 degrees  rotated search display so that the stimuli appeared in an implied
      "sky" plane, and with search in a random layout implying no depth. This was
      tested for stimuli with, or without, curvature discontinuities, that have
      previously been shown to be strong cues for shape analysis. Surprisingly, no
      advantage of the ground plane over the sky plane was observed, while a strong
      effect of layout regularity was seen. Similarly, in experiment 2 there was little
      effect of placing the stimuli on an implied wall plane compared to the ground or
      the sky. The results are not explained by assuming that curvature discontinuities
      are such strong cues that they overshadow any effect of depth-plane, since there
      was a strong effect of regular versus random layout, which should also have
      disappeared under this account. The results argue instead for a very strong
      effect of layout regularity, unrelated to environmental regularities in
      evolutionary history, since there was no ground-plane benefit.

PMID- 24025996
TI  - Substitution reactions on a hypercoordinated main-group element encapsulated in a
      pentacapped trigonal prismatic copper cage.
AB  - Compound 1, [Cu11(MU9-Br)(MU3-Br)3{S2P(O(i)Pr)2}6](+), containing the first MU9
      bromide at the center of a pentacapped trigonal-prismatic copper skeleton, was
      isolated from the reaction of [Cu(CH3CN)4](PF6), NH4[S2P(O(i)Pr)2], and Bu4NBr in
      11:6:4 ratios in methanol. Treatment of 1 with Bu4NI resulted in a complete
      replacement of four bromides to yield a corresponding iodo analogue
      {Cu11(I)(I)3[S2P(O(i)Pr)2]6}(+), 2. The central bromide and iodide in 1 and 2 can
      be replaced by a sulfide generated in situ from Na2S2O3 to produce [Cu11(MU9
      S)(MU3-X)3{S2P(O(i)Pr)2}6] (X = Br, 3; I, 4). All four compounds displayed
      interesting photoluminescent properties.

PMID- 24025997
TI  - The influence of antenatal exposure to phthalates on subsequent female
      reproductive development in adolescence: a pilot study.
AB  - We hypothesised that antenatal exposure to ubiquitous phthalates may lead to an
      earlier menarche and a lower prevalence of polycystic ovarian syndrome (PCOS) and
      polycystic ovarian morphology (PCO) in adolescence. The Western Australian
      Pregnancy Cohort (Raine) Study recruited 3000 women at 18 weeks of gestation in
      1989-1991, 1377 had antenatal serum stored without thawing at -80  degrees C. An
      unselected subset was evaluated in the early follicular phase for PCO and PCOS by
      ultrasound and serum evaluation in adolescence. Serum was analysed for anti
      Mullerian hormone (AMH), inhibin B, sex hormone binding globulin (SHBG),
      testosterone, androstenedione and DHEAS. Four hundred microlitres of the frozen
      maternal serum underwent isotope-diluted liquid chromatography-tandem mass
      spectrometry, with preceding enzymatic deconjugation followed by solid-phase
      extraction to determine phthalate exposure. Two hundred and forty four girls
      attended assessment and most common phthalate metabolites were detectable in the
      majority of the 123 samples available. Several phthalates were negatively
      associated with maternal SHBG, and associations with maternal androgens were less
      consistent. The sum of the metabolites of di-(2-ethylhexyl) phthalate was
      associated with a non-significant tendency towards an earlier age at menarche
      (P=0.069). Uterine volume was positively associated with mono-(carboxy-iso-octyl)
      phthalate (P=0.018). Exposure to monoethyl phthalate (MEP) and the sum of all
      phthalate metabolites (Sigmaall phth.m) were protective against PCOS in
      adolescence (P=0.001 and P=0.005 respectively). There were negative associations
      of MEP with PCO (P=0.022) and of MEP with serum AMH (P=0.031). Consequently, our
      data suggest that antenatal exposure to environmental phthalates may be
      associated with oestrogenic and/or anti-androgenic reproductive effects in
      adolescent girls. 

PMID- 24025998
TI  - Bilateral dacryocystoceles in a pregnant woman.
AB  - The authors describe, for the first time, bilateral, sequential large
      dacryocystoceles during pregnancy and review the literature for this
      presentation. A 26-year-old, 15-week pregnant woman presented with OD epiphora,
      diplopia, and pain in the setting of an inferomedial orbital mass. Surgical
      exploration and histopathology were consistent with a dacryocystocele, and a
      dacryocystorhinostomy was curative. She returned at 34-week gestation, with an
      identical presentation on the left side. Review of the literature reveals that
      dacryocystoceles occasionally present in adults; however, bilateral involvement
      may be unusual. Bilateral dacryocystoceles have not been previously reported in a
      pregnant woman. 

PMID- 24025999
TI  - Intralesional bleomycin: a potential treatment for refractory orbital
      lymphangiomas.
AB  - The authors present 4 cases of orbital lymphangioma that had not responded to
      conventional therapy but responded positively to intralesional bleomycin
      injections. In this retrospective case series, patients were recruited from the
      Oculoplastics Clinic at Tygerberg Academic Hospital with histologic and/or
      radiologic evidence of microcystic and macrocytic deep and/or combined orbital
      lymphangioma. All 4 cases had multiple prior intralesional steroid injections.
      Three had previous intralesional bevacizumab, and 2 had prior radiotherapy. Under
      anesthesia, a solution containing 1 IU bleomycin per milliliter saline together
      with 2% lignocaine was injected in the lesion. Retreatments were performed every
      4 to 8 weeks if needed. A total of 1 to 6 intralesional bleomycin injections were
      used to treat the 4 cases. All 4 cases showed significant regression with marked
      clinical improvement. No systemic or ophthalmic side effects were noted. From
      this series, the authors suggest that intralesional bleomycin injections might be
      considered as a first-line agent in cases of untreated microcystic and macrocytic
      deep and/or superficial orbital lymphangiomas or as an alternative treatment
      option for refractory cases. 

PMID- 24026000
TI  - Epithelioid hemangioma of the orbit or angiolymphoid hyperplasia with
      eosinophilia.
AB  - A patient was referred to the department for an incidentally discovered right
      orbital mass on MRI. After surgical excision, histopathologic examination led to
      the diagnosis of epithelioid hemangioma, a tumor rarely located in the orbit,
      whose main histopathologic feature is an exuberant proliferation of small
      vascular channels lined by enlarged endothelial cells. The clinical
      characteristics and histopathology of epithelioid hemangioma allow
      differentiation with Kimura disease, angiosarcoma, intravascular papillary
      endothelial hyperplasia, and other vascular tumors that share the common feature
      of an abnormal proliferation of endothelial cells. Although epithelioid
      hemangioma is extremely rare, it should be considered in the differential
      diagnosis of orbital tumors. 

PMID- 24026001
TI  - Dacryops in the setting of a Boston type II keratoprosthesis.
AB  - Dacryops of the lacrimal tissue can develop under diverse circumstances. Recent
      evidence suggests that scarring or obstruction of the lacrimal ducts may lead to
      their dilatation and formation of a cystic structure. Patients who undergo
      repeated orbital surgery may therefore be at greater risk of dacryops formation.
      In this report, a patient who underwent multiple corneal and glaucoma procedures
      including Boston type II keratoprosthesis, after acid burns to both eyes, is
      described. Over time, a fluid-filled collection developed in the lower orbit. On
      surgical exploration and incision, fluid was drained from a cystic lesion which
      abutted the lacrimal gland and spanned the upper and lower orbits. The lesion was
      removed and was proven by histopathology and immunohistochemistry to be dacryops.
      This is the first known case of dacryops associated with Boston type II
      keratoprosthesis. 

PMID- 24026002
TI  - [Amebic liver abscess and late recurrence with no travel in an endemic area].
AB  - Amebic liver abscess is the main complication of amebic dysentery. Recurrences
      after treatment and apparent healing are very uncommon. The purpose of this
      report is to describe the case of a patient with a very late relapse of an amebic
      liver abscess, 10 years after the first episode. This recurrence seems due to an
      incomplete initial treatment. This case illustrates the reason for and importance
      of complying with the current therapeutic strategy: nitroimidazole followed by a
      luminal agent to eradicate intestinal amebic colonization. 

PMID- 24026003
TI  - Exploring public awareness and perceptions of palliative care: a qualitative
      study.
AB  - BACKGROUND: Research suggests that the public appear to be confused about the
      meaning of palliative care. Given the ageing population and associated increase
      in the number of patients requiring palliative care, it is vital to explore the
      public's understanding of this concept. Health-promoting palliative care seeks to
      translate hospice and palliative care ideals into broader public health practice.
      AIM: To explore public perceptions of palliative care and identify strategies to
      raise awareness. DESIGN: An exploratory qualitative approach. PARTICIPANTS: Semi
      structured telephone interviews were undertaken (N = 50) with members of the
      public who volunteered to participate in the study. The interviews focused on
      knowledge and perceptions of palliative care, expectations of palliative care
      services and the identification of strategies to raise public awareness of
      palliative care. The interviews were audio recorded and content analysed.
      RESULTS: Most participants had a general knowledge of palliative care, largely
      influenced by their own personal experience. They identified that palliative care
      was about caring for people who were dying and maintaining comfort in the last
      days of life. Participant's expectations of services included the following:
      holistic support, symptom management, good communication and practical support to
      enable choice and carer support. Key aspects identified for promoting palliative
      care were the development of understanding and use of the term itself and
      targeted educational strategies. CONCLUSION: Experience of palliative care
      generates understanding in the general public who also have ideas for increasing
      knowledge and awareness. The findings can inform policymakers about strategies to
      raise public awareness of palliative care.

PMID- 24026004
TI  - Duality between the dynamics of line-like brushes of point defects in 2D and
      strings in 3D in liquid crystals.
AB  - We analyze the dynamics of dark brushes connecting point vortices of strength +/
      1 formed in the isotropic-nematic phase transition of a thin layer of nematic
      liquid crystals, using a crossed polarizer set up. The evolution of the brushes
      is seen to be remarkably similar to the evolution of line defects in a three
      dimensional nematic liquid crystal system. Even phenomena like the
      intercommutativity of strings are routinely observed in the dynamics of brushes.
      We test the hypothesis of a duality between the two systems by determining
      exponents for the coarsening of total brush length with time as well as shrinking
      of the size of an isolated loop. Our results show scaling behavior for the brush
      length as well as the loop size with corresponding exponents in good agreement
      with the 3D case of string defects. 

PMID- 24026005
TI  - Ground states of the Ising model on an anisotropic triangular lattice: stripes
      and zigzags.
AB  - A complete solution of the ground-state problem for the Ising model on an
      anisotropic triangular lattice with the nearest-neighbor interactions in a
      magnetic field is presented. It is shown that this problem can be reduced to the
      ground-state problem for an infinite chain with the interactions up to the second
      neighbors. In addition to the known ground-state structures (which correspond to
      full-dimensional regions in the parameter space of the model), new structures are
      found (at the boundaries of these regions), in particular, zigzagging stripes
      similar to those observed experimentally in colloidal monolayers. Though the
      number of parameters is relatively large (four), all the ground-state structures
      of the model are constructed and analyzed and therefore the paper can be
      considered as an example of a complete solution of a ground-state problem for
      classical spin or lattice-gas models. The paper can also help to verify the
      correctness of some results obtained previously by other authors and concerning
      the ground states of the model under consideration. 

PMID- 24026006
TI  - A highly selective probe for human cytochrome P450 3A4: isoform selectivity,
      kinetic characterization and its applications.
AB  - Bufalin 5beta-hydroxylation was found to be an isoform-specific biotransformation
      probe substrate for cytochrome P450 3A4 (CYP3A4). The probe reaction was well
      characterized and it can be used for measuring the real catalytic activities of
      CYP3A4 from different enzyme sources. 

PMID- 24026008
TI  - Heart development and regeneration via cellular interaction and reprogramming.
AB  - The heart consists of many types of cells, including cardiomyocytes, vascular
      cells, neural cells, and cardiac fibroblasts. Adult cardiomyocytes are terminally
      differentiated cells, and loss of cardiomyocytes as a result of heart damage is
      irreversible. To regenerate damaged hearts and restore cardiac function,
      understanding the cellular and molecular basis of heart development is of
      considerable importance. Although it is well known that heart function is tightly
      regulated by cell-cell interactions, their roles in heart development are not
      clear. Recent studies, including ours, identified important roles of cell-cell
      interactions in heart development and function. The balance between neural
      chemoattractants and chemorepellents secreted from cardiomyocytes determines
      cardiac nervous development. Nerve growth factor is a potent chemoattractant
      synthesized by cardiomyocytes, whereas Sema3a is a neural chemorepellent
      expressed specifically in the subendocardium. Disruption of this molecular
      balance induces disorganized cardiac innervation and may lead to sudden cardiac
      death due to lethal arrhythmias. Cardiac fibroblasts, of which there are large
      populations in the heart, secrete high levels of specific extracellular matrix
      and growth factors. Embryonic cardiac fibroblast-specific secreted factors
      collaboratively promote mitotic activity of embryonic cardiomyocytes and
      expansion of ventricular chambers during cardiogenesis. More recently, utilizing
      knowledge of the regulatory mechanisms of heart development, we found that
      cardiac fibroblasts can be directly reprogrammed into cardiomyocyte-like cells in
      vitro and in vivo by gene transfer of cardiac-specific transcription factors.
      Understanding the mechanisms of heart development and cardiac reprogramming
      technology may provide new therapeutic approaches for heart disease in the
      future. 

PMID- 24026007
TI  - Mn3[Co(CN)6]2@SiO2 core-shell nanocubes: novel bimodal contrast agents for MRI
      and optical imaging.
AB  - Nanoprobes with dual modal imaging of magnetic resonance imaging (MRI) and two
      photon fluorescence (TPF) can serve as promising platforms for clinical
      diagnosis. A wide range of molecules and nanoparticles have been investigated as
      agents for contrast enhanced MRI and fluorescence imaging in cancer diagnosis.
      However, a single material with dual modal imaging of MRI and TPF is rarely
      reported. We found that Mn3[Co(CN)6]2@SiO2 nanocubes can serve as agents for both
      T1- and T2-weighted MRI, and TPF imaging. The nanocubes coated with silica to
      form Mn3[Co(CN)6]2@SiO2 core-shell nanocubes were readily internalized by cells
      without showing cytotoxicity. In vitro tests, the core-shell nanocubes display
      relatively high longitudinal (r1) and transverse (r2) relaxivities, they also
      manifest a remarkable T1 and T2 contrast effects at in-vivo imaging of internal
      organs in Mice. Moreover, the core-shell nanocubes could offer high-resolution
      cell fluorescence imaging by two-photon excitation (720 nm) or by conventional
      fluorescence with 403- or 488-nm excitation.

PMID- 24026009
TI  - Survival of foodborne pathogens on inshell walnuts.
AB  - The survival of Salmonella enterica Enteritidis PT 30 or five-strain cocktails of
      S. enterica, Escherichia coli O157:H7, and Listeria monocytogenes was evaluated
      on inshell walnuts during storage. Inshell walnuts were separately inoculated
      with an aqueous preparation of the pathogens at levels of 10 to 4 log CFU/nut,
      dried for 24 h, and then stored at either 4  degrees C or ambient conditions (23
      25  degrees C, 25-35% relative humidity) for 3 weeks to more than 1 year. During
      the initial 24-h drying period, bacterial levels declined by 0.7 to 2.4 log
      CFU/nut. After the inoculum dried, further declines of approximately 0.1 log
      CFU/nut per month of Salmonella Enteritidis PT 30 levels were observed on inshell
      walnuts stored at 4  degrees C; at ambient conditions the rates of decline ranged
      from 0.55 to 2.5 log CFU/nut per month. Rates of decline were generally greater
      during the first few weeks of storage, particularly at lower inoculum levels. The
      survival of the five-strain cocktails inoculated at very low levels (under 400
      CFU/nut) was determined during storage at ambient conditions. The pathogens could
      be recovered by either enumeration or enrichment from most samples throughout the
      3-month storage period; reductions in bacterial levels from the beginning to end
      of storage were 0.7, 0.2, and 2.3 log CFU/nut for Salmonella, E. coli O157:H7,
      and L. monocytogenes, respectively. For 6% of all nut samples (14 of 234
      samples), pathogens were isolated from the second but not first 24-h enrichment,
      suggesting that bacterial cells were viable but not easily culturable. Salmonella
      inoculated walnuts were exposed for 2 min to water or a 3% solution of sodium
      hypochlorite (to mimic commercial brightening) either 24 h or 7 days after
      inoculation; treated nuts were dried for 24h and held at ambient conditions.
      Salmonella levels were reduced by less than 0.5 log or 2.4 to 2.6 log CFU/nut on
      water- or chlorine- treated walnuts, respectively, regardless of postinoculation
      treatment time. Additional reductions of 2.6 and 2.1 log CFU/nut were observed
      for water- and chlorine-treated walnuts, respectively, after storage for 2 weeks
      at ambient conditions. Bacterial foodborne pathogens are capable of long-term
      survival on the surface of inshell walnuts even when initial levels are low.

PMID- 24026010
TI  - Antifungal activity of food additives in vitro and as ingredients of
      hydroxypropyl methylcellulose-lipid edible coatings against Botrytis cinerea and
      Alternaria alternata on cherry tomato fruit.
AB  - The antifungal activity of food additives or 'generally recognized as safe'
      (GRAS) compounds was tested in vitro against Botrytis cinerea and Alternaria
      alternata. Radial mycelial growth of each pathogen was measured in PDA Petri
      dishes amended with food preservatives at 0.2, 1.0, or 2.0% (v/v) after 3, 5, and
      7 days of incubation at 25  degrees C. Selected additives and concentrations were
      tested as antifungal ingredients of hydroxypropyl methylcellulose (HPMC)-lipid
      edible coatings. The curative activity of stable coatings was tested in in vivo
      experiments. Cherry tomatoes were artificially inoculated with the pathogens,
      coated by immersion about 24 h later, and incubated at 20  degrees C and 90% RH.
      Disease incidence and severity (lesion diameter) were determined after 6, 10, and
      15 days of incubation and the 'area under the disease progress stairs' (AUDPS)
      was calculated. In general, HPMC-lipid antifungal coatings controlled black spot
      caused by A. alternata more effectively than gray mold caused by B. cinerea.
      Overall, the best results for reduction of gray mold on cherry tomato fruit were
      obtained with coatings containing 2.0% of potassium carbonate, ammonium
      phosphate, potassium bicarbonate, or ammonium carbonate, while 2.0% sodium
      methylparaben, sodium ethylparaben, and sodium propylparaben were the best
      ingredients for coatings against black rot.

PMID- 24026011
TI  - Antibacterial effect of light emitting diodes of visible wavelengths on selected
      foodborne pathogens at different illumination temperatures.
AB  - The antibacterial effect of light emitting diodes (LEDs) in the visible region
      (461, 521 and 642 nm) of the electromagnetic spectrum was investigated on
      Escherichia coli O157:H7, Salmonella typhimurium, Listeria monocytogenes and
      Staphylococcus aureus. The irradiances of the 461, 521 and 642 nm LEDs were 22.1,
      16 and 25.4 mW/cm2, respectively. Bacterial cultures suspended in tryptic soy
      broth were illuminated by 10-watt LEDs at a distance of 4.5 cm for 7.5h at 20, 15
      and 10  degrees C. Regardless of the bacterial strains, bacterial inactivation
      was observed with the range of 4.6-5.2 logCFU/ml at 10 and 15  degrees C after
      illumination with the 461 nm LED, while illumination with the 521 nm LED resulted
      in only 1.0-2.0 log reductions after 7.5h. On the other hand, no antibacterial
      effect was observed using the 642 nm LED treatment. The photodynamic inactivation
      by 461 and 521 nm LEDs was found to be greater at the set temperatures of 10 and
      15  degrees C than at 20  degrees C. The D-values for the four bacterial strains
      at 10 and 15  degrees C after the illumination of 461 nm LED ranged from 1.29 to
      1.74 h, indicating that there was no significant difference in the susceptibility
      of the bacterial strains to the LED illumination between 10 and 15  degrees C,
      except for L. monocytogenes. Regardless of the illumination temperature,
      sublethal injury was observed in all bacterial strains during illumination with
      the 461 and the 521 nm LED and the percentage of injured cells increased as the
      treatment time increased. Thus, the results show that the antibacterial effect of
      the LEDs was highly dependent on the wavelength and the illumination temperature.
      This study suggests the potential of 461 and 521 nm LEDs in combination with
      chilling to be used as a novel food preservation technology.

PMID- 24026012
TI  - Axl mediates acquired resistance of head and neck cancer cells to the epidermal
      growth factor receptor inhibitor erlotinib.
AB  - Elevated expression and activity of the epidermal growth factor receptor (EGFR)
      is associated with development and progression of head and neck cancer (HNC) and
      a poor prognosis. Clinical trials with EGFR tyrosine kinase inhibitors (e.g.,
      erlotinib) have been disappointing in HNC. To investigate the mechanisms
      mediating resistance to these agents, we developed an HNC cell line (HN5-ER) with
      acquired erlotinib resistance. In contrast to parental HN5 HNC cells, HN5-ER
      cells exhibited an epithelial-mesenchymal (EMT) phenotype with increased
      migratory potential, reduced E-cadherin and epithelial-associated microRNAs
      (miRNA), and elevated vimentin expression. Phosphorylated receptor tyrosine
      kinase profiling identified Axl activation in HN5-ER cells. Growth and migration
      of HN5-ER cells were blocked with a specific Axl inhibitor, R428, and R428
      resensitized HN5-ER cells to erlotinib. Microarray analysis of HN5-ER cells
      confirmed the EMT phenotype associated with acquired erlotinib resistance, and
      identified activation of gene expression associated with cell migration and
      inflammation pathways. Moreover, increased expression and secretion of
      interleukin (IL)-6 and IL-8 in HN5-ER cells suggested a role for inflammatory
      cytokine signaling in EMT and erlotinib resistance. Expression of the tumor
      suppressor miR-34a was reduced in HN5-ER cells and increasing its expression
      abrogated Axl expression and reversed erlotinib resistance. Finally, analysis of
      302 HNC patients revealed that high tumor Axl mRNA expression was associated with
      poorer survival (HR = 1.66, P = 0.007). In summary, our results identify Axl as a
      key mediator of acquired erlotinib resistance in HNC and suggest that therapeutic
      inhibition of Axl by small molecule drugs or specific miRNAs might overcome anti
      EGFR therapy resistance.

PMID- 24026013
TI  - Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen
      IgG response and lethal toxin neutralization activity.
AB  - We describe the Bacillus anthracis protective antigen IgG antibody response and
      the B. anthracis lethal toxin neutralization activity to a delayed dose of
      anthrax vaccine adsorbed (AVA, BioThrax((r))) using validated assays. 373
      individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they
      received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti
      PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost.
      Geometric mean anti-PA IgG concentration (GMC) was 1.66 MUg/mL before and 887.82
      MUg/mL after the boost (P<0.0001). The proportion of individuals with four-fold
      increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG
      levels and B. anthracis lethal toxin neutralization activity are induced when an
      AVA dose is delayed as long as two years. These data support continuing with the
      vaccination schedule when a dose is delayed as long as two years rather than
      restarting the series.

PMID- 24026014
TI  - A nanopore machine promotes the vectorial transport of DNA across membranes.
AB  - The transport of nucleic acids through membrane pores is a fundamental biological
      process that occurs in all living organisms. It occurs, for example, during the
      import of viral DNA into the host cell or during the nuclear pore complex
      mediated transport of mRNA in and out the cell nucleus and has implications in
      nucleic acid drug delivery and gene therapy. Here we describe an engineered DNA
      transporter that is able to recognize and chaperone a specific DNA molecule
      across a biological membrane under a fixed transmembrane potential. The
      transported DNA strand is then released by a simple mechanism based on DNA strand
      displacement. This nanopore machine might be used to separate or concentrate
      nucleic acids or to transport genetic information across biological membranes. 

PMID- 24026015
TI  - Diet-induced weight gain produces a graded increase in behavioral responses to an
      acute immune challenge.
AB  - Sickness behaviors and fever during infection constitute an adaptive and tightly
      regulated mechanism designed to efficiently clear the invading pathogen from the
      body. Recent literature has demonstrated that changes in energy status can
      profoundly affect the fever response to an acute immune challenge. The purpose of
      the present study was to investigate whether the exacerbating effect of diet
      induced obesity (DIO) on the LPS-induced fever response demonstrated previously
      would generalize to other sickness behaviors and, further, whether incremental
      changes in body weight would influence these responses. Results showed that DIO
      male Wistar rats exhibited a higher number of sickness symptoms for a longer
      period after lipopolysaccharide (LPS) injection (100MUg/kg) than lean rats.
      Similarly, they showed a more prolonged fever and a delayed recovery from LPS
      induced suppression of social interaction. No difference in locomotor activity
      was observed between obese and lean groups. Comparisons among groups that varied
      in body weight showed that an 11% increase in body weight was sufficient to
      increase the number and duration of sickness symptoms displayed after an LPS
      injection and that the severity of sickness symptoms increased with increasing
      body weight. Together these data suggest that DIO can have profound effects on
      multiple behavioral responses to an acute immune challenge placing obese
      organisms at higher risk of the consequences of prolonged inflammation. 

PMID- 24026017
TI  - Mussel inspired surface functionalization of electrospun nanofibers for bio
      applications.
AB  - Electrospinning technology has been widely recognized because of its ability to
      synthesize nanoscale fibers that are structurally similar to fibrillar structure
      of the natural extracellular matrix (ECM). Rendering the nanofiber surface to be
      biofunctional is critical for the successful application of the electrospinning
      technology in biomedical applications. Limitations in typical conjugation
      chemistry and physical adsorption procedures might be overcome by using
      polydopamine (pDA) coating inspired by adhesive proteins secreted by marine
      mussels. This perspective paper attempts to highlight an emerging area of the
      unique combination of electrospinning with pDA surface functionalization. The
      scientific progress and understandings of pDA coating chemistry mechanisms,
      coating processes and characterization with aids of nanoscale analytical
      techniques are reviewed and discussed. The intrinsic biomimetic morphological
      characteristics of the electrospun nanofibers united with the unique advantages
      of the pDA associated bio-functionalization have endowed a range of successful
      applications, especially in the interesting and important field of
      bioengineering. 

PMID- 24026016
TI  - Synthesis and biological evaluation of N-(2-fluorophenyl)-2beta
      deoxyfuconojirimycin acetamide as a potent inhibitor for alpha-l-fucosidases.
AB  - In this study we revealed that the addition of an N-phenylacetamide substituent
      to the C-1 position of 1-deoxyfuconojirimycin (DFJ) can lead to highly potent
      inhibitors of alpha-l-fucosidases. A structure-activity relationship study showed
      that a fluoro group on the phenyl ring greatly increased its potency and
      selectivity. In contrast the addition of two or three fluoro groups decreased
      their inhibition potency. Consequently, N-(2-fluorophenyl)-2beta-DFJ acetamide
      (18j) was found to display very potent and selective inhibition of bovine kidney,
      rat epididymis, and human lysosome alpha-l-fucosidases, with IC50 value of 0.012,
      0.044, and 0.0079MUM respectively. It is noteworthy that our designed N-phenyl
      2beta-DFJ acetamide derivative exhibited about 18-fold stronger effects on human
      lysosomal alpha-l-fucosidase than original DFJ and it occupied the active-site of
      this enzyme. We therefore expect that this compound may find applications in new
      therapeutic trials against genetic deficiency disorders. 

PMID- 24026018
TI  - Doping alkaline-earth: a strategy of stabilizing hexagonal GdF3 at room
      temperature.
AB  - Hexagonal GdF3 is a more efficient phosphor host compared with the traditional
      orthorhombic form but the hexagonal phase is thermodynamically unstable at room
      temperature. Herein, we present a strategy to stabilize hexagonal GdF3 by doping
      with alkaline-earth ions in a mild hydrothermal reaction system. The selection of
      the dopant, effect of the dopant amount and the mechanism of the phase transition
      was discussed in detail. The luminescence variation of GdF3:Eu was demonstrated
      to verify the phase transformation. Furthermore, the upconversion luminescence of
      the Sr-doped and undoped GdF3:Yb/Er was investigated. 

PMID- 24026019
TI  - This is not your father's VA.

PMID- 24026020
TI  - The multiuniverse transition in superfluid 3He.
AB  - The symmetry-breaking phase transitions of the universe and of superfluid (3)He
      may lead to the formation of different states with different order parameters. In
      both cases the energy potential below the transition temperature has a
      complicated multidimensional profile with many local minima and saddle points,
      which correspond to different states. Consequently, not only topological defects,
      but also islands of different metastable states can be created. Using (3)He we
      can analyse the properties and experimental consequences of such transitions and,
      in particular, the first-order phase transition between the two low symmetry
      states. 

PMID- 24026021
TI  - On the chemical state of Co oxide electrocatalysts during alkaline water
      splitting.
AB  - Resonant inelastic X-ray scattering and high-resolution X-ray absorption
      spectroscopy were used to identify the chemical state of a Co electrocatalyst in
      situ during the oxygen evolution reaction. After anodic electrodeposition onto
      Au(111) from a Co(2+)-containing electrolyte, the chemical environment of Co can
      be identified to be almost identical to CoOOH. With increasing potentials, a
      subtle increase of the Co oxidation state is observed, indicating a non
      stoichiometric composition of the working OER catalyst containing a small
      fraction of Co(4+) sites. In order to confirm this interpretation, we used
      density functional theory with a Hubbard-U correction approach to compute X-ray
      absorption spectra of model compounds, which agree well with the experimental
      spectra. In situ monitoring of catalyst local structure and bonding is essential
      in the development of structure-activity relationships that can guide the
      discovery of efficient and earth abundant water splitting catalysts. 

PMID- 24026022
TI  - Sudden sensorineural hearing loss associated with chronic periodontitis: a
      population-based study.
AB  - OBJECTIVE: Although plenty of researchers have reported systemic effects
      originating from chronic periodontitis (CP) on potentially distal inflammatory
      processes, such as those leading to coronary heart disease, cerebrovascular
      disease, and cancer, no study has reported the association between CP and sudden
      sensorineural hearing loss (SSNHL). The present study explored the association
      between CP and SSNHL using a large, population-based dataset in Taiwan. STUDY
      DESIGN: A case-control study. SETTING: Taiwan. PATIENTS: We used administrative
      claims data from the Taiwan National Health Insurance program to identify 2,436
      subjects with SSNHL and to randomly select 7,308 controls. MAIN OUTCOME MEASURES:
      A conditional logistic regression analysis was conducted to calculate the odds
      ratio (OR) for having been previously diagnosed with CP between cases and
      controls. RESULTS: In total, 1,663 (17.1%) of the 9,744 sampled subjects had
      received a CP diagnosis before the index date; 520 (21.4%) were cases and 1143
      (15.6%) were controls. The chi2 test suggested that there was a significant
      difference in the prevalence of previous SSNHL between cases and controls (p <
      0.001). The conditional logistic regression revealed after adjusting for
      hypertension, diabetes, hyperlipidemia, renal disease, coronary heart disease,
      obesity, and stroke, the OR of having previously received a CP diagnosis among
      cases was 1.44 (95% CI = 1.29~1.63) that of controls. CONCLUSION: This study
      found that SSNHL was significantly associated with a previous diagnosis of CP.
      Further prospective studies are warranted to confirm our findings and clarify the
      underlying pathomechanism.

PMID- 24026023
TI  - Self-reported symptoms in patients with idiopathic sudden sensorineural hearing
      loss.
AB  - OBJECTIVE: This study evaluated self-reported symptoms in patients with
      idiopathic sudden sensorineural hearing loss (ISSHL). STUDY DESIGN: Cross
      sectional study. SETTING: Multicenter clinical investigation in 9 university
      hospitals. PATIENTS: In total, 140 patients with ISSHL and 24 patients with
      unilateral sensorineural hearing loss (USHL; control) were included. MAIN OUTCOME
      MEASURES: A questionnaire on symptoms of ISSHL was distributed and the Short-Form
      Health Survey (Version 2) was used for assessing the quality of life. RESULTS: In
      response to questions on hearing difficulty, many of patients in both groups
      experienced symptoms. In response to questions on hearing-related discomfort, a
      significantly higher number of patients with ISSHL experienced symptoms compared
      with those with USHL. Compared with a high incidence of tinnitus in patients with
      ISSHL, very low incidence of tinnitus was observed in those with USHL.In the
      multiple linear regression analysis, hearing-related discomfort was the sole
      significant factor on the Mental Component Summary scores of the Short-Form
      Health Survey (Version 2). CONCLUSION: Many patients with ISSHL experience
      several symptoms such as hearing difficulty, hearing-related discomfort,
      tinnitus, and anxiety. Hearing-related discomfort strongly affected the quality
      of life in patients with ISSHL.

PMID- 24026024
TI  - Hearing outcomes in functional surgery for middle ear malformations.
AB  - OBJECTIVES: To standardize the information for families of children having
      functional surgery for middle ear malformations, we describe the audiometric
      results of the subgroup of patients with the most favorable anatomic conditions:
      viable auditory canal, intact tympanic membrane, mobile stapes, and corresponding
      to a Jahrsdoerfer score of 8 or higher. STUDY DESIGN: Case series, tertiary
      referral center. METHODS: Charts of patients undergoing functional surgery for
      congenital middle ear malformations were reviewed for demographic data,
      preoperative Jahrsdoerfer score, ossicular chain status, type of ossiculoplasty,
      and audiometric data before and 6 months postsurgery. RESULTS: Eighteen
      consecutive interventions were performed on 13 patients (average age of 9 years,
      8 girls and 5 boys) between 2004 and 2011. The ossiculoplasties performed were as
      follows: incus repositioning (4), double-layer tragal cartilage (5), intact
      native chain reconstruction (3), and partial ossicular prosthesis (6). Mean air
      bone gap (ABG) was 40.8 +/- 12.4 dB preoperatively and 20.9 +/- 12.9 dB
      postoperatively (p < 0.0001). Preoperative and postoperatively mean air
      conduction PTA thresholds were 49.9 +/- 9.5 and 30.0 +/- 14.1 dB, respectively (p
      < 0.0001). All ears operated on except one had air conduction improvement. There
      were no complications. CONCLUSION: Functional surgery for congenital middle ear
      malformations gives variable hearing outcomes. In this study, with the most
      favorable anatomic conditions, 12 ears (67%) of 18 had air conduction improvement
      below 30 dB.

PMID- 24026025
TI  - Benign paroxysmal positional vertigo after surgical drilling of the temporal
      bone.
AB  - OBJECTIVE: To present the clinical characteristics of secondary BPPV after
      surgical drilling of the temporal bone. STUDY DESIGN: Retrospective study.
      SETTING: Tertiary referral academic medical center. PATIENTS: Ten patients who
      developed BPPV after surgical procedure of temporal bone drilling were identified
      from 965 subjects who underwent surgical drilling of the temporal bone at Seoul
      National University Bundang Hospital. The localization and lateralization of BPPV
      were based on positional test using video eye movement recording system and
      videonystagmography. MAIN OUTCOME MEASURES: Onset of BPPV after surgery,
      distributions of involved semicircular canals, response to particle repositioning
      maneuver and factors that may influence the development of secondary BPPV after
      surgical drilling of the temporal bone. RESULTS: Onset of positional vertigo was
      mostly within 3 days except 1 case (sixth postoperative day). Postoperative BPPV
      was usually in the contralateral ear in 9 cases (90%), which occurred
      predominantly on the contralateral horizontal canal in 8 patients (80%).
      Positional vertigo was resolved after repositioning maneuvers in every case. None
      of them showed aggravation of bone conduction threshold. CONCLUSION: The
      incidence of BPPV after surgical drilling of the temporal bone was around 1%, and
      the horizontal semicircular canal of the contralateral ear was predominantly
      involved. Head position during surgery (head restriction to contralateral ear
      down) as well as limitation of head movement due to compressive mastoid bandage
      after surgery seems to be responsible for such predominance.

PMID- 24026026
TI  - Removal of hydroxyapatite cement from cadaveric temporal bones after
      transtemporal surgery.
AB  - HYPOTHESIS: To determine the best method of removing hydroxyapatite cement from
      the temporal bone in the postoperative period. BACKGROUND: The advent of
      hydroxyapatite cement in neurotologic surgery of the temporal bone has
      dramatically decreased the rate of postoperative cerebrospinal fluid leaks.
      However, there is no literature currently available on how to manage these
      patients in the setting of postoperative hematomas of the cerebellopontine angle.
      METHODS: Nine cadaveric temporal bones were obtained that had previously
      undergone translabyrinthine approach drilling in an academic temporal bone lab.
      Fascia and adipose tissue were placed medial to the facial nerve and the temporal
      bone was then filled with hydroxyapatite cement to the level of the cortex.
      Removal of hydroxyapatite cement was undertaken using a Freer elevator, mastoid
      bone curette, and finally, a drill in sequential fashion. This occurred at 9
      predetermined time intervals from 1 to 30 hours and was timed in each case.
      RESULTS: Removal using the freer and curette failed in each case, and the drill
      was ultimately used to remove the hydroxyapatite cement in all cases. The time to
      reach the packed fascia and adipose tissue varied from 3 to 6 minutes, average
      time is 4.27 +/- 0.84 minutes. CONCLUSION: Although hydroxyapatite cement has
      dramatically decreased the rate of postoperative cerebrospinal fluid leak in
      translabyrinthine surgery, its use has also brought a new set of considerations.
      This study suggests that hydroxyapatite cement removal in the setting of
      postoperative hematoma after translabyrinthine surgery would require drilling
      rather than bedside incisional opening alone. Like standard craniotomy
      approaches, postoperative hemorrhage management requires intraoperative drainage.

PMID- 24026027
TI  - Measurements of the position relationship between the inferior margin of the oval
      window and the endosteum of basal cochlear turn in histologic and HRCT study.
AB  - HYPOTHESIS: To identify the optimum and safe location histologically for drilling
      and fenestration on promontory inferior to the oval window in stapedectomy. The
      value of application of high-resolution computed tomography (HRCT) scanning and
      multiple-planar reconstruction (MPR) for this purpose is also assessed. METHODS:
      By means of histologic sections and HRCT scanning and MPR for coronal image,
      measurements were conducted on 3 perpendicular planes in temporal bone sections
      through the anterior, posterior, and midpoint of the inferior margin of the oval
      window, respectively. RESULTS: The promontory bone inferior to the posterior
      portion of the oval window is thickest, which has an average thickness of about
      1.1 mm. The endosteum of the basal turn here is deepest under the promontory,
      which has an average height of about 0.2 mm above the plane of footplate, whereas
      the distance between the inferior margin of the oval window and the endosteum
      here is no more than 0.3 mm. The coincidence rate of the measurements by HRCT and
      histology is up to 90.5%. CONCLUSION: Relatively safe location for bone of the
      promontory removal should be restricted in the posterior portion inferior to the
      oval window, and the burr should be lifted laterally while drilling. Preoperative
      HRCT scanning and MPR for coronal image would offer a valuable reference to
      estimate the safe area for bone of the promontory removal in stapedectomy.

PMID- 24026028
TI  - Observation of apoptosis and bone lamella structures in the human mastoid.
AB  - HYPOTHESIS: To investigate the localization of apoptotic cells and the lamellar
      bone structure in mastoid bone tissue, focusing on the mechanism of the
      development of mastoid pneumatization in humans. BACKGROUND: The biological
      mechanism of poor development of the mastoid air cells found in patients with
      otitis media (OM) has not yet been fully clarified, as there have been few
      immunohistochemical research studies to examine the cell biology involved.
      METHODS: We evaluated the localization of apoptotic cells and the lamellar bone
      structure in 112 human mastoid bones harvested during various ear surgeries from
      57 patients with OM and 55 patients without OM. We used the TdT-mediated dUTP
      nick end-labeling (TUNEL) method and a polarizing microscope for observing the
      apoptotic cells and lamellar bone structure, respectively. RESULTS: The TUNEL
      positive cell ratio in an arbitrary 500 cells in the specimen (apoptotic index:
      AI) was 13.8 in the healthy group and 1.2 in the OM group (Mann-Whitney U test, p
      < 0.001). From their localization, these apoptotic cells were considered to be
      osteocytes. The observation of lamellar structures revealed many eroded surfaces
      in the circumference of the appositional bone in the healthy group. In contrast,
      apposition of bone without an eroded surface was evident in the bone
      circumference in the OM group. CONCLUSION: Apoptosis of osteocytes was
      significantly suppressed in the mastoid bone of the OM patients. Apoptotic
      osteocytes may be one of the signals of bone resorption in the process of
      development of the mastoid air cells. The lamellar structure of the mastoid bone
      suggested that poor development of the mastoid air cells was caused by decreased
      resorption of the appositional bone.

PMID- 24026030
TI  - Letter to the editor re: "Correlation of computed tomography with histopathology
      in otosclerosis", Quesnel et al. Otol Neurotol 2013; 34(1);22-8.

PMID- 24026029
TI  - In response to letter to the editor: Lyme disease associated with sudden
      sensorineural hearing loss: case report and literature review.

PMID- 24026031
TI  - In response to letter to the editor: "Correlation of computed tomography with
      histopathology in otoslcerosis", Quesnel et al. Otol Neurotol 2013; 34(1):22-8.

PMID- 24026032
TI  - Osteoma of stapes in the middle ear: a case report.

PMID- 24026033
TI  - Otitis media and facial paralysis as presenting symptoms of a primary middle ear
      sarcoidosis.

PMID- 24026034
TI  - Matrine induction of reactive oxygen species activates p38 leading to caspase
      dependent cell apoptosis in non-small cell lung cancer cells.
AB  - Non-small cell lung carcinoma (NSCLC) is one of the most refractory cancers in
      the clinic; it is insensitive to chemotherapy and is usually excised. However,
      screening natural compounds from herbs is also considered a possible method for
      its therapy. In the present study, we investigated whether matrine, a natural
      compound isolated from Sophora flavescens Ait. and exerting an inhibitory effect
      on lung cancer cells, also indicates inhibition on NSCLC cells and elucidated its
      molecular mechanism. Firstly, it is confirmed that matrine induces apoptosis of
      human NSCLC cells with anti-apoptotic factors inhibited and dependent on caspase
      activity. In addition, we found that matrine increases the phosphorylation of p38
      but not its total protein, and inhibition of the p38 pathway with SB202190
      partially prevents matrine-induced apoptosis. Furthermore, matrine generates
      reactive oxygen species (ROS) in a dose- and time-dependent manner, which is
      reversed by pretreatment with N-acetyl-L-cysteine (NAC). Additionally, inhibition
      of cell proliferation and increase of phosphorylation of p38 was also partially
      reversed by NAC. Collectively, matrine activates p38 pathway leading to a caspase
      dependent apoptosis by inducing generation of ROS in NSCLC cells and may be a
      potential chemical for NSCLC. 

PMID- 24026035
TI  - Is gravitation your friend or foe?

PMID- 24026036
TI  - The possibility of resistant hypertension during the treatment of hypertensive
      patients.
AB  - Patients with poorly controlled hypertension despite taking at least three
      different kinds of anti-hypertensive drugs, including diuretics, are considered
      to have resistant hypertension (RH). The prevalence of RH was reported to be 13%
      in the Japanese J-HOME study. The incidences of RH in younger and older Japanese
      individuals should be prospectively investigated in the near future. RH is
      associated with poor outcomes and various cardiovascular events. In addition, it
      is frequently associated with older age, obesity, sleep apnea, long-term
      hypertension, diabetes, dyslipidemia, reduced renal function, microalbuminuria
      and left ventricular hypertrophy. Some cases of RH exhibit high levels of
      aldosterone and cortisol, suggesting that endocrine hypertension should be ruled
      out among RH patients. Carotid baroreceptor activation and renal sympathetic
      denervation have recently been developed as treatments for RH. In conclusion, we
      should consider the possibility of RH during the treatment of hypertensive
      patients who do not achieve appropriate blood pressure control, in order to avoid
      the early onset of fatal cardiovascular events and reduce medical costs. 

PMID- 24026037
TI  - Efficacy of losartan and carvedilol on central hemodynamics in hypertensives: a
      prospective, randomized, open, blinded end point, multicenter study.
AB  - Renin-angiotensin system (RAS) blockers have shown clinical outcomes superior to
      those of the beta (beta)-blocker atenolol, despite similar reductions in the
      peripheral blood pressure (BP), perhaps because of different impacts on central
      hemodynamics. However, few comparative studies of RAS blockers and newer
      vasodilating beta-blockers have been performed. We compared the central
      hemodynamic effects of losartan and carvedilol in a prospective, randomized,
      open, blinded end point study. Of the 201 hypertensive patients enrolled, 182
      (49.6+/-9.9 years, losartan group=88 and carvedilol group=94) were analyzed.
      Carotid-femoral pulse wave velocity (cfPWV), aortic augmentation index (AIx), AIx
      corrected for a heart rate (HR) of 75 beats per minute (AIx@HR75) and central BP
      were measured noninvasively at baseline and after a 24-week treatment regimen
      with losartan or carvedilol. After 24 weeks, there were no between-group
      differences in the brachial BP, cfPWV, AIx@HR75 or central BP changes, except for
      a more favorable AIx effect with losartan. The changes in all measured metabolic
      and inflammatory parameters were also not significantly different between the two
      groups, except for uric acid. Losartan and carvedilol showed generally comparable
      effects on central hemodynamic indices, metabolic profile, inflammatory
      parameters and peripheral arterial pressure with a 24-week treatment. 

PMID- 24026039
TI  - Can two be better than one? Dual RAS blockade in patients with type 2 diabetes
      and overt nephropathy in the age of ONTARGET and ALTITUDE.

PMID- 24026038
TI  - Effects of dual blockade of the renin-angiotensin system on renal and
      cardiovascular outcomes in type 2 diabetes with overt nephropathy and
      hypertension in the ORIENT: a post-hoc analysis (ORIENT-Hypertension).
AB  - Combination therapy with angiotensin II receptor blockers and angiotensin
      converting enzyme inhibitors (ACEIs) requires further evaluation in patients with
      diabetic nephropathy and hypertension. In a post hoc analysis of the Olmesartan
      Reducing Incidence of Endstage renal disease in diabetic Nephropathy Trial with
      hypertension, we examined the effects of olmesartan on renal and cardiovascular
      outcomes in the presence or absence of an ACEI. Among 563 patients randomized to
      receive either olmesartan (n = 280) or placebo (n = 283), 73.5% (n = 414)
      received a concomitant ACEI. Compared with placebo, olmesartan significantly
      reduced proteinuria in both the ACEI-treated and non-ACEI-treated groups. The
      respective changes in the urinary protein creatinine ratio in the olmesartan
      treated and placebo-treated groups were -32.6% and +21.1% without an ACEI (P =
      0.001) and -17.0% and +2.2% with an ACEI (P = 0.028). In the olmesartan group,
      115 patients developed primary renal outcomes (41.1%) compared with 129 (45.6%)
      in the placebo group (hazard ratio (HR): 0.97, P = 0.787). The respective HRs in
      the ACEI-treated and non-ACEI-treated groups were 1.02 (P = 0.891) and 0.84 (P =
      0.450). 40 olmesartan-treated patients (14.3%) and 53 placebo-treated patients
      (18.7%) developed secondary cardiovascular outcomes (HR: 0.65, P = 0.042). The
      respective HRs in the ACEI-treated and non-ACEI-treated groups were 0.69 (P =
      0.129) and 0.51 (P = 0.129). Olmesartan was well tolerated. Dual blockade
      treatment caused more hyperkalemia than monotherapy. In patients with diabetic
      nephropathy and hypertension, olmesartan significantly reduced proteinuria,
      independent of ACEI treatment and cardiovascular outcome but failed to show
      additional renal benefit compared with ACEI treatment alone. The cardiovascular
      benefit of dual treatment requires further evaluation.

PMID- 24026040
TI  - Blood pressure variability: does speed matter?

PMID- 24026041
TI  - The interaction of transient receptor potential melastatin 7 with macrophages
      promotes vascular adventitial remodeling in transverse aortic constriction rats.
AB  - Transient receptor potential melastatin 7 (TRPM7), a novel channel kinase, has
      been recently identified in the vasculature. However, its regulation and function
      in vascular diseases remain poorly understood. To address this lack of knowledge,
      we sought to examine whether TRPM7 can mediate the vascular remodeling process
      induced by pressure overload in the right common carotid artery proximal to the
      band (RCCA-B) in male Sprague-Dawley rats with transverse aortic constriction
      (TAC). The contribution of TRPM7 to amplified vascular remodeling after TAC was
      tested using morphometric and western blot analyses. Pressure overload-induced
      vascular wall thickening, especially in the adventitia, was readily detected in
      RCCA-B. The TRPM7 level was increased with a simultaneous accumulation of
      macrophages in the adventitia of RCCA-B, whereas the anti-inflammatory molecule
      annexin-1, a TRPM7 downstream target, was decreased. After the addition of the
      TRPM7 inhibitor 2-aminoethoxydiphenyl borate (2-APB), significant reductions in
      macrophage accumulation as well as the expression of monocyte chemotactic protein
      1, SM-22-alpha and collagen I were observed, whereas annexin-1 was rescued.
      Finally, in cultured vascular adventitial fibroblasts treated with macrophage
      conditioned medium, there were marked increases in the expression of TRPM7 and SM
      22-alpha with a concurrent reduction in annexin-1 expression; these effects were
      largely prevented by treatment with 2-APB and specific anti-TRPM7 small
      interfering RNA. Our findings provide the first demonstration of the potential
      regulatory roles of TRPM7 in the vascular inflammation, pressure overload
      mediated vascular adventitial collagen accumulation and cell phenotypic
      transformation in TAC rats. The targeting of TRPM7 has potential therapeutic
      importance for vascular diseases. 

PMID- 24026043
TI  - Steeper increases in body mass index during childhood correlate with blood
      pressure elevation in adolescence: a long-term follow-up study in a Japanese
      community.
AB  - The aim of this study was to clarify the relationship between long-term changes
      in body mass index (BMI) during childhood and adolescent blood-pressure levels in
      a general Japanese population. We used health report data from 900 Japanese
      children between 1983 and 2007. After adjusting for baseline BMI and other
      confounding factors multivariate linear regression analyses were performed to
      examine the relationship between changes in BMI (DeltaBMI) over a 6-year period
      (6-12 years) and blood pressure once children reached ages 14 or 15. Sub-group
      analyses were also performed to ascertain the relationship between DeltaBMI and
      blood pressure at 9th grade for children who had been in the bottom BMI tertile
      at 1st grade. Endpoint blood-pressure levels in boys (systolic and diastolic) and
      girls (systolic) from the group whose BMIs increased the most were significantly
      higher than those from the group whose BMIs increased the least (P<0.05, analysis
      of variance). After adjustment for baseline BMI and school-entrance year, the
      former group showed higher blood pressure at the endpoint than the latter
      (P<0.05, multiple regression analysis). Further adjustment for baseline blood
      pressure also showed similar results in a combined-sex analysis (n=592). Higher
      DeltaBMI was associated with higher SBP9 even in children whose BMI was in the
      lowest tertile at baseline after adjustment for sex and school-entrance year
      (P=0.02, multiple regression analysis). Steeper BMI increases during primary
      school lead to adolescent increases in blood pressure even if baseline BMI is
      low. Growth during childhood should be carefully managed. 

PMID- 24026044
TI  - Nanoporous Sr-rich strontium titanate: a stable and superior photocatalyst for H2
      evolution.
AB  - A synthetic route to prepare nanoporous Sr-rich strontium titanate (Sr : Ti ~
      1.03) with a high surface area is reported. The as-obtained porous nanomaterial
      serves as a stable and superior photocatalyst for H2 evolution. 

PMID- 24026042
TI  - High sodium augments angiotensin II-induced vascular smooth muscle cell
      proliferation through the ERK 1/2-dependent pathway.
AB  - Angiotensin II (Ang II)-induced vascular injury is exacerbated by high-salt
      diets. This study examined the effects of high-sodium level on Ang II-induced
      cell proliferation in rat vascular smooth muscle cells (VSMCs). The cells were
      cultured in a standard medium containing 137.5 mmol l(-1) of sodium. The high
      sodium medium (140 mmol l(-1)) contained additional sodium chloride.
      Extracellular signal-regulated kinase (ERK) 1/2 phosphorylation was determined by
      western blot analysis. Cell proliferation was evaluated by [(3)H]-thymidine
      incorporation. Ang II (100 nmol l(-1)) significantly increased ERK 1/2
      phosphorylation and cell proliferation in the both medium containing standard
      sodium and high sodium. High-sodium level augmented Ang II-induced ERK 1/2
      phosphorylation and cell proliferation compared with standard sodium. Pre
      treatment with candesartan (1 MUmol l(-1), Ang II type 1 receptor blocker) or
      PD98095 (10 MUmol l(-1), ERK kinase iinhibitor) abolished the proliferative
      effect induced by high sodium/Ang II. Pre-treatment with 5-N,N-hexamethylene
      amiloride (30 MUmol l(-1), Na(+)/H(+) exchanger type 1 (NHE-1) inhibitor), but
      not SN-6 (10 MUmol l(-1), Na(+)/Ca(2+) exchanger inhibitor) or ouabain (1 mmol l(
      1), Na(+)/K(+)-ATPase inhibitor) attenuated ERK 1/2 phosphorylation or cell
      proliferation. Osmotic pressure or chloride had no effect on Ang II-induced
      proliferative changes. High-sodium level did not affect Ang II receptor
      expression. Ang II increased intracellular pH via NHE-1 activation, and high
      sodium level augmented the pH increase induced by Ang II. These data suggest that
      high-sodium level directly augments Ang II-induced VSMC proliferation through NHE
      1- and ERK 1/2-dependent pathways and may offer new insights into the mechanisms
      of vascular remodeling by high-sodium/Ang II.

PMID- 24026045
TI  - A scoping literature review of the provision of orthoses and prostheses in
      resource-limited environments 2000-2010. Part one: considerations for success.
AB  - STUDY DESIGN: Literature Review BACKGROUND: We estimate that over 29 million
      people worldwide in resource-limited environments (RLEs) are in need of orthotic
      and prosthetic (O&P) devices and services. OBJECTIVES: Our goal was to ascertain
      the current state of O&P provision in RLEs and identify factors that may lead to
      more successful O&P provision. METHODS: We conducted a comprehensive scoping
      literature review of all information related to O&P provision in RLEs published
      from 2000 to 2010. We targeted Vietnam, Cambodia, Tanzania, Malawi, Colombia, and
      the Navajo Nation, but also included information about developing countries in
      general. We searched academic databases and grey literature. We extracted
      information from each article in the areas of design, manufacturing,
      distribution, service provision, and technology transfer. RESULTS: We identified
      commonly reported considerations and strategies for O&P provision from 431
      articles. Analysis of expert consensus documents revealed recurring themes for
      improving O&P provision. We found that some suggestions from the consensus
      documents are being followed, but many are overlooked or have not yet been
      implemented. CONCLUSIONS: Areas for improvement include conducting field testing
      during the design process, providing services to rural environments, offering
      follow-up services, considering government collaboration, and encouraging an
      active role of the orthosis/prosthesis user. Outcomes and research studies will
      be further discussed in Part Two.

PMID- 24026051
TI  - Evidence that the novel receptor FGFRL1 signals indirectly via FGFR1.
AB  - Fibroblast growth factor (FGF) receptor-like protein 1 (FGFRL1) is a recently
      discovered member of the FGF receptor (FGFR) family. Similar to the classical
      FGFRs, it contains three extracellular immunoglobulin-like domains and interacts
      with FGF ligands. However, in contrast to the classical receptors, it does not
      contain any intracellular tyrosine kinase domain and consequently cannot signal
      by transphosphorylation. In mouse kidneys, FgfrL1 is expressed primarily at
      embryonic stages E14-E15 in regions where nascent nephrons develop. In this
      study, we used whole-mount in situ hybridization to show the spatial pattern of
      five different Fgfrs in the developing mouse kidney. We compared the expression
      pattern of FgfrL1 with that of other Fgfrs. The expression pattern of FgfrL1
      closely resembled that of Fgfr1, but clearly differed from that of Fgfr2-Fgfr4.
      It is therefore conceivable that FgfrL1 signals indirectly via Fgfr1. The
      mechanisms by which FgfrL1 affects the activity of Fgfr1 remain to be elucidated.

PMID- 24026052
TI  - Feeling the force: returning haptic signals influence effort inference during
      motor coordination.
AB  - Our brain is known to automatically optimize effort expenditure during motor
      coordination, such that for example, during bimanual braking of a bicycle, a well
      oiled brake will automatically be used more than a corroded, heavy brake. But how
      does our brain infer the effort expenditure? All previous motor coordination
      models have believed that the effort in a task is known precisely to our brain,
      solely from the motor commands it generates. Here we show that this belief is
      incorrect. Through experiments and simulation we exhibit that in addition to the
      motor commands, the returning haptic signals play a crucial role in the inference
      of the effort during a force sharing task. Our results thus elucidate a
      previously unknown sensory-motor association that has major ramifications for our
      understanding of motor coordination and provides new insights into how sensory
      modifications due to ergonomics, stroke and disease can affect motor coordination
      in humans. 

PMID- 24026053
TI  - Chromosomes: Architectural cohesin.

PMID- 24026054
TI  - Transcription: Proteasome power to Def1.

PMID- 24026056
TI  - [Economic impact of skin-lightening products on household income in sub-Saharan
      Africa: the case of Senegal].
AB  - INTRODUCTION: As throughout sub-Saharan Africa, the use of skin-lightening (or
      brightening or bleaching) products is widespread in Senegal (67%). Although the
      medical and social determinants of this phenomenon have been documented, its cost
      is poorly defined. Thus, this work aims to evaluate the economic effects of skin
      bleaching on women's income. METHODOLOGY: A cross-sectional, quantitative, and
      descriptive survey was conducted in 2010 (October 7 to November 8) among women
      consulting for outpatient care at a reference dermatology clinic for
      complications related to use of skin-lightening products. We calculated the
      direct costs (products) and indirect costs (transportation costs, medical fees,
      dermatological treatment of complications). The social damage (pain and suffering
      and esthetics) was assessed. RESULTS: This study included 65 women; their mean
      age was 33 years and 26% had not attended school. In all, 52% were merchants, 29%
      housewives, 9% civil servants, and 5% students. The average duration of product
      use was 9 years, and the mean age at onset of use, 23 years. Most (80%) had a low
      income (<100,000 FCFA or US $204). The total monthly income of the 65 women in
      the study was 5,675,000 CFA (US $ 11,582). The total monthly cost of skin
      lightening for them was 1081,658 CFA (US $ 2207), that is, 19% of their total
      income. The esthetic harm was categorized as moderate by 20% and high by 22%.
      CONCLUSION: This study opens perspectives for further studies of the intangible
      costs of skin bleaching and for increasing awareness of the complications and
      social damage induced.

PMID- 24026055
TI  - Chaperone machines for protein folding, unfolding and disaggregation.
AB  - Molecular chaperones are diverse families of multidomain proteins that have
      evolved to assist nascent proteins to reach their native fold, protect subunits
      from heat shock during the assembly of complexes, prevent protein aggregation or
      mediate targeted unfolding and disassembly. Their increased expression in
      response to stress is a key factor in the health of the cell and longevity of an
      organism. Unlike enzymes with their precise and finely tuned active sites,
      chaperones are heavy-duty molecular machines that operate on a wide range of
      substrates. The structural basis of their mechanism of action is being unravelled
      (in particular for the heat shock proteins HSP60, HSP70, HSP90 and HSP100) and
      typically involves massive displacements of 20-30 kDa domains over distances of
      20-50 A and rotations of up to 100 degrees . 

PMID- 24026057
TI  - Involvement of androgens in ovarian health and disease.
AB  - In women, ovary and adrenal gland produce androgens. Androgens are essential
      drivers of the primordial to antral follicle development, prior to serving as
      substrate for estrogen production in the later stages of folliculogenesis.
      Androgens play a crucial role in the follicular-stromal intertalk by fine tuning
      the extracellular matrix and vessel content of the ovarian stroma. Local auto-and
      paracrine factors regulate androgen synthesis in the pre-antral follicle.
      Androgen excess is a hallmark of polycystic ovary syndrome and is a key
      contributor in the exaggerated antral follicle formation, stromal hyperplasia and
      hypervascularity. Hyperandrogenaemia overrides the follicular-stromal dialog,
      resulting in follicular arrest and disturbed ovulation. On the other hand,
      androgen deficiency is likely to have a negative impact on fertility as well, and
      further research is needed to examine the benefits of androgen-replacement
      therapy in subfertility. 

PMID- 24026059
TI  - [Photodynamic therapy of bladder cancer. A new option].
AB  - BACKGROUND: Bladder cancer (BCa) is the third most common tumor in Germany.
      Currently, resection therapy for superficial BCa (Ta, CIS) includes photodynamic
      diagnostics (PDD) using HEXVIX(r) for improved assessment of tumor spread. Trials
      using these photosensitizers for photodynamic therapy (PDT) showed only limited
      success. Especially low tissue penetration due to short-wave excitation was a
      limiting factor. METHODS: This study which was funded by the German Research
      Foundation (DFG) examined the feasibility of the novel photosensitizer
      tetrahydroporphyrin-tetratosylate (THPTS) for PDT in a rat bladder cancer model.
      RESULTS: As THPTS is very effectively excitable at a near infrared wavelength of
      760 nm it is within the so-called phototherapeutic window and allows tissue
      penetration of up to 15 mm. Thus THPTS can also be used for PDT of larger, solid
      tumors as was previously demonstrated for other tumor entities. Therefore,
      effective treatment of even muscle-invasive bladder cancer (>=T2) may become an
      option using THPTS. In this current study the effectiveness and safety of THPTS
      PDT was examined in an orthotopic bladder cancer rat model.

PMID- 24026060
TI  - [Proteome-based diagnostic and prognostic biomarkers of prostate cancer].
AB  - BACKGROUND: Due to comprehensive PSA screening, the incidence for prostate cancer
      (PCa) is rising. Therefore, there is an urgent need for improved PCa diagnostics
      and prognostic tools to differentiate between insignificant and aggressive, fast
      growing tumors. METHODS: With the proteome-based method presented here, we were
      able to distinguish PCa from BPH, chronic prostatitis and healthy controls with
      83 % sensitivity and 67 % specificity. Furthermore, the methods discerned
      advanced PCa from local, organ-confined PCa in a group of patients with gleason
      score 7 (80 % sensitivity, 82 % specificity). RESULTS: Our proteomic approach is
      based on the analysis of low molecular weight polypeptides, identified as the
      endpoint of the naturally occuring liquefaction cascade in seminal plasma. For
      the first time using seminal plasma as a source, we analysed a complex network of
      interacting proteases and specific inhibitors, reflecting tumor biology
      specificity. Our diagnostic and prognostic tool is robust and easy to handle, and
      therefore it is well suitable for the laboratory and medical practice.

PMID- 24026061
TI  - [Translational uroradio-oncology].
AB  - BACKGROUND: Recent developments and innovations in modern radiation oncology
      enable radiation oncologists to deliver a biologically, physically and
      technically stratified individualized treatment. In urological oncology,
      radiotherapy can be offered as a valid treatment alternative for a number of
      tumors, such as prostate cancer or urothelial cancer/bladder cancer. METHODS: By
      improving the precision of radiotherapy, significant improvement in tumor control
      can be achieved, coupled with a reduction of the risk of treatment-related side
      effects. Techniques such as high precision radiotherapy and combinations of
      radiation and modern imaging, such as image-guided radiotherapy (IGRT) and
      adaptive radiotherapy (ART), make daily individually tailored treatment possible.
      CONCLUSIONS: In the future the biological characteristics of tumors and of normal
      tissue as well as molecular markers can be used for treatment stratification.

PMID- 24026062
TI  - [Urologists meet in Berlin. Martin Stolze (1900-1989) and the urologist
      convention in 1959 in East and West Berlin].
AB  - Scientific meetings are a major part of policy in science and within the
      scientific community and furthermore they have a major influence on medical and
      lay communities. Prominent examples for this are the presidential networks and
      the opening speeches in which the function of science within the society is
      presented in a special manner. The last joint meeting of the German Society for
      Urology (DGU) in East and West Germany was instrumentalized by the rivalry of the
      two systems during the Cold War but was also a brilliant presentation of the
      newly established German Urology after World War II and its scientific force. 

PMID- 24026058
TI  - [Urine cytology - update 2013. A systematic review of recent literature].
AB  - Urine cytology is an important element of the diagnosis and follow-up of
      urothelial carcinomas and is recommended in most relevant guidelines. Urine-based
      marker systems are advocated as an adjunct to or a replacement of urine cytology.
      Urine cytology also has its place in the diagnosis of benign diseases. This
      systematic review describes and discusses the literature on urine cytology
      published since 2010. 

PMID- 24026068
TI  - Optical control of hard X-ray polarization by electron injection in a laser
      wakefield accelerator.
AB  - Laser-plasma particle accelerators could provide more compact sources of high
      energy radiation than conventional accelerators. Moreover, because they deliver
      radiation in femtosecond pulses, they could improve the time resolution of X-ray
      absorption techniques. Here we show that we can measure and control the
      polarization of ultra-short, broad-band keV photon pulses emitted from a laser
      plasma-based betatron source. The electron trajectories and hence the
      polarization of the emitted X-rays are experimentally controlled by the pulse
      front tilt of the driving laser pulses. Particle-in-cell simulations show that an
      asymmetric plasma wave can be driven by a tilted pulse front and a non-symmetric
      intensity distribution of the focal spot. Both lead to a notable off-axis
      electron injection followed by collective electron-betatron oscillations. We
      expect that our method for an all-optical steering is not only useful for plasma
      based X-ray sources but also has significance for future laser-based particle
      accelerators. 

PMID- 24026069
TI  - Radiographic evaluation of INBONE total ankle arthroplasty: a retrospective
      analysis of 30 cases.
AB  - OBJECTIVES: The objectives of this work were to retrospectively describe the
      radiographic assessment of INBONE total ankle arthroplasty in 30 patients using
      validated linear and angular measurements and to correlate these findings with
      the final surgical outcome over a 2-year follow-up period. MATERIALS AND METHODS:
      Thirty consecutive patients (21 females, nine males; mean age, 64.8 years)
      underwent INBONE total ankle arthroplasty during 2007-2011. After IRB approval, a
      retrospective pre- and post-operative radiographic analysis was performed using
      validated linear and angular measurements. The pre- and post-operative assessment
      included the tibial angle, talar angle, tibial slope, and coronal deformity. Post
      operative measurements also included the talocalcaneal angle, joint space height,
      talar height, lateral tibial component angle, lateral talar component angle, and
      anteroposterior tibial component angle. The post-operative bone loss,
      subluxation, positioning, and subsidence were also assessed. Statistical analysis
      was performed using two-sample t test and Fisher's exact test. RESULTS: Out of 30
      patients, 23 had a successful clinical outcome with intact prosthesis at a 2-year
      follow-up. The only variables with significant correlation (p < 0.05) to the post
      surgical outcome were the lateral talar component angle (p = 0.002) and the mean
      difference between pre- and post-operative tibial slope (p = 0.001). The coronal
      deformity had significant mean difference between pre- and post-operative values
      (p < 0.001); however, it lacked a significant correlation to the final surgical
      outcome. None of the categorical variables had a significant correlation with
      post-surgical outcome. CONCLUSIONS: In our retrospective study, only the lateral
      talar component angle and the mean difference between the pre- and post-operative
      tibial slope had significant correlation with post-surgical outcome in INBONE
      ankle arthroplasty. These measurements may be helpful in radiographic assessment
      of the INBONE ankle arthroplasty.

PMID- 24026070
TI  - Semimembranosus tendon avulsion fracture of the posteromedial tibial plateau
      associated with posterior cruciate ligament tear and capsular rupture.
AB  - Semimembranosus tendon avulsion fractures are an uncommon occurrence and are
      often associated with anterior cruciate ligament (ACL) and medial meniscus tears.
      We present the imaging features of an unusual case of semimembranosus avulsion
      fracture of the posteromedial tibial plateau associated with posterior cruciate
      ligament (PCL) tear, medial meniscus tear, and capsular rupture in a 26-year-old
      man with a football injury. 

PMID- 24026071
TI  - Vitamin D and the heart.
AB  - Vitamin D receptors (VDR) are found in cells throughout the cardiovascular
      system. A variety of experimental studies indicate that the liganded VDR may play
      an important role in controlling cardiac hypertrophy and fibrosis, regulating
      blood pressure, and suppressing the development of atherosclerosis. Some, but not
      all, observational studies in humans provide support for these experimental
      findings, raising the possibility that vitamin D or its analogs might prove
      useful therapeutically in the prevention or treatment of cardiovascular disease.

PMID- 24026074
TI  - Roux-en-Y gastric bypass surgery reduces bone mineral density and induces
      metabolic acidosis in rats.
AB  - Roux-en-Y gastric bypass (RYGB) surgery leads to bone loss in humans, which may
      be caused by vitamin D and calcium malabsorption and subsequent secondary
      hyperparathyroidism. However, because these conditions occur frequently in obese
      people, it is unclear whether they are the primary causes of bone loss after
      RYGB. To determine the contribution of calcium and vitamin D malabsorption to
      bone loss in a rat RYGB model, adult male Wistar rats were randomized for RYGB
      surgery, sham-operation-ad libitum fed, or sham-operation-body weight-matched.
      Bone mineral density, calcium and phosphorus balance, acid-base status, and
      markers of bone turnover were assessed at different time points for 14 wk after
      surgery. Bone mineral density decreased for several weeks after RYGB. Intestinal
      calcium absorption was reduced early after surgery, but plasma calcium and
      parathyroid hormone levels were normal. 25-hydroxyvitamin D levels decreased,
      while levels of active 1,25-dihydroxyvitamin D increased after surgery. RYGB rats
      displayed metabolic acidosis due to increased plasma lactate levels and increased
      urinary calcium loss throughout the study. These results suggest that initial
      calcium malabsorption may play a key role in bone loss early after RYGB in rats,
      but other factors, including chronic metabolic acidosis, contribute to
      insufficient bone restoration after normalization of intestinal calcium
      absorption. Secondary hyperparathyroidism is not involved in postoperative bone
      loss. Upregulated vitamin D activation may compensate for any vitamin D
      malabsorption.

PMID- 24026073
TI  - Early postweaning exercise improves central leptin sensitivity in offspring of
      rat dams fed high-fat diet during pregnancy and lactation.
AB  - Maternal high-fat (HF) diet has long-term consequences on the metabolic phenotype
      of the offspring. Here, we determined the effects of postweaning exercise in
      offspring of rat dams fed HF diet during gestation and lactation. Pregnant
      Sprague-Dawley rats were maintained on chow or HF diet throughout gestation and
      lactation. All pups were weaned onto chow diet on postnatal day (PND) 21. At 4 wk
      of age, male pups were given free access to running wheels (RW) or remained
      sedentary (SED) for 3 wk, after which all rats remained sedentary, resulting in
      four groups: CHOW-SED, CHOW-RW, HF-SED, and HF-RW. Male HF offspring gained more
      body weight by PND7 compared with CHOW pups and maintained this weight difference
      through the entire experiment. Three weeks of postweaning exercise did not affect
      body weight gain in either CHOW or HF offspring, but reduced adiposity in HF
      offspring. Plasma leptin was decreased at the end of the 3-wk running period in
      HF-RW rats but was not different from HF-SED 9 wk after the exercise period
      ended. At 14 wk of age, intracerebroventricular injection of leptin suppressed
      food intake in CHOW-SED, CHOW-RW, and HF-RW, while it did not affect food intake
      in HF-SED group. At death, HF-RW rats also had higher leptin-induced phospho
      STAT3 level in the arcuate nucleus than HF-SED rats. Both maternal HF diet and
      postweaning exercise had effects on hypothalamic neuropeptide and receptor mRNA
      expression in adult offspring. Our data suggest that postweaning exercise
      improves central leptin sensitivity and signaling in this model.

PMID- 24026075
TI  - Pronounced in vivo hemoglobin polymerization in red blood cells of Gulf toadfish:
      a general role for hemoglobin aggregation in vertebrate hemoparasite defense?
AB  - Two human hemoglobin (Hb) variants, Hb C and Hb S, are known to protect against
      Plasmodium falciparum malaria and have evolved repeatedly in malaria endemic
      areas. Both aggregate to insoluble crystals (Hb C) or polymers (Hb S) under
      certain physiological conditions, impair parasite growth, and may facilitate
      retention of infected red blood cells (RBCs) in the spleen. Given the profound
      effects of parasites on host evolution in general, and that RBC Hb concentration
      is often close to its solubility limit throughout vertebrates, similar mechanisms
      may operate in nonhuman vertebrates. Here we show exercise-induced, profound in
      vivo Hb polymerization in RBCs of the Gulf toadfish. Hb aggregation was closely
      associated with the extent of plasma acidosis, fully reversible, and without any
      signs of hemolysis or anemia. Our literature analysis suggests that aggregation
      prone Hbs may be relatively old, evolved multiple times in nonhuman vertebrates,
      show enhanced aggregation during hemoparasite infections, and can be uncovered in
      vivo by splenectomy. We discuss the working hypothesis that widespread Hb
      aggregation within several vertebrate groups may be the result of ongoing or past
      selection pressure against RBC parasites. Further comparative studies of these
      evolutionary old systems may provide valuable insights into hemoparasite
      susceptibility and reservoir potential of livestock and companion animals but
      also into human malaria and sickle cell disease.

PMID- 24026072
TI  - Central losartan attenuates increases in arterial pressure and expression of
      FosB/DeltaFosB along the autonomic axis associated with chronic intermittent
      hypoxia.
AB  - Chronic intermittent hypoxia (CIH) increases mean arterial pressure (MAP) and
      FosB/DeltaFosB staining in central autonomic nuclei. To test the role of the
      brain renin-angiotensin system (RAS) in CIH hypertension, rats were implanted
      with intracerebroventricular (icv) cannulae delivering losartan (1 MUg/h) or
      vehicle (VEH) via miniosmotic pumps and telemetry devices for arterial pressure
      recording. A third group was given the same dose of losartan subcutaneously (sc).
      Two groups of losartan-treated rats served as normoxic controls. Rats were
      exposed to CIH or normoxia for 7 days and then euthanized for
      immunohistochemistry. Intracerebroventricular losartan attenuated CIH-induced
      increases in arterial pressure during CIH exposure (0800-1600 during the light
      phase) on days 1, 6, and 7 and each day during the normoxic dark phase.
      FosB/DeltaFosB staining in the organum vasculosum of the lamina terminalis
      (OVLT), median preoptic nucleus (MnPO), paraventricular nucleus of the
      hypothalamus (PVN), the rostral ventrolateral medulla (RVLM), and the nucleus of
      the solitary tract (NTS) was decreased in icv losartan-treated rats. Subcutaneous
      losartan also reduced CIH hypertension during the last 2 days of CIH and produced
      bradycardia prior to the effect on blood pressure. Following sc losartan,
      FosB/DeltaFosB staining was reduced only in the OVLT, MnPO, PVN, and NTS. These
      data indicate that the central and peripheral RAS contribute to CIH-induced
      hypertension and transcriptional activation of autonomic nuclei and that the
      contribution of the central RAS is greater during the normoxic dark phase of CIH
      hypertension.

PMID- 24026076
TI  - Increased cytokine and chemokine gene expression in the CNS of mice during heat
      stroke recovery.
AB  - Heat stroke (HS) is characterized by a systemic inflammatory response syndrome
      (SIRS) consisting of profound core temperature (Tc) changes in mice.
      Encephalopathy is common at HS collapse, but inflammatory changes occurring in
      the brain during the SIRS remain unidentified. We determined the association
      between inflammatory gene expression changes in the brain with Tc disturbances
      during HS recovery in mice. Gene expression changes of heat shock protein
      (HSP)72, heme oxygenase (hmox1), cytokines (IL-1beta, IL-6, TNF-alpha),
      cyclooxygenase enzymes (COX-1, COX-2), chemokines (MCP-1, MIP-1alpha, MIP-1beta,
      CX3CR1), and glia activation markers (CD14, aif1, vimentin) were examined in the
      hypothalamus (HY) and hippocampus (HC) of control (Tc ~ 36.0 degrees C) and HS
      mice at Tc,Max (42.7 degrees C), hypothermia depth (HD; 29.3 +/- 0.4 degrees C),
      and fever (37.8 +/- 0.3 degrees C). HSP72 (HY<HC) and IL-1beta (HY only) were the
      only genes that showed increased expression at Tc,Max. HSP72 (HY < HC), hmox1 (HY
      < HC), cytokine (HY = HC), and chemokine (HY = HC) expression was highest at HD
      and similar to controls during fever. COX-1 expression was unaffected by HS,
      whereas HD was associated with approximately threefold increase in COX-2
      expression (HY only). COX-2 expression was not increased during fever and
      indomethacin (COX inhibitor) had no effect on this Tc response indicating fever
      is regulated by other inflammatory pathways. CD14, aif1, and vimentin activation
      at HD coincided with maximal cytokine and chemokine expression suggesting glia
      cells are a possible source of brain cytokines and chemokines during HS recovery.
      The inflammatory gene expression changes during HS recovery suggest cytokines
      and/or chemokines may be initiating development or rewarming from hypothermia,
      whereas fever pathway(s) remain to be elucidated.

PMID- 24026077
TI  - Treatment of thoracic wounds with adapted vacuum therapy.
AB  - This is a report of seven cases of infected thoracic wounds treated with an
      adapted low-cost vacuum therapy in the Thoracic Surgery Unit of Santa Marcelina
      Hospital. The vacuum system used was designed and adapted to our hospital due to
      financial limitations on the acquisition of commercial kits. The vacuum-assisted
      closure kit used in this study consisted of chlorhexidine sponges (which are
      usually used for antisepsis of the surgical team), a 16F nasogastric tube, and
      two sterile adhesive films (OPSITE) for surgical field reinforcement. The mean
      duration of vacuum therapy was 13.4 days (range, 10-20 days), with an average of
      three dressing changes (range, 1-5). After treatment with vacuum-assisted
      closure, three wounds (3/7) were closed with simple primary sutures, one of the
      lesions (1/7) was closed by muscle flap rotation, and three wounds (3/7) healed
      by second intention. This adapted vacuum therapy was safe and easy to apply in
      our institution, including its use in patients with thoracostomies. 

PMID- 24026078
TI  - Agonist anti-human CD27 monoclonal antibody induces T cell activation and tumor
      immunity in human CD27-transgenic mice.
AB  - The CD70/CD27 pathway plays a significant role in the control of immunity and
      tolerance, and previous studies demonstrated that targeting murine CD27 (mCD27)
      with agonist mAbs can mediate antitumor efficacy. We sought to exploit the
      potential of this pathway for immunotherapy by developing 1F5, a fully human IgG1
      mAb to human CD27 (hCD27) with agonist activity. We developed transgenic mice
      expressing hCD27 under control of its native promoter for in vivo testing of the
      Ab. The expression and regulation of hCD27 in hCD27-transgenic (hCD27-Tg) mice
      were consistent with the understood biology of CD27 in humans. In vitro, 1F5
      effectively induced proliferation and cytokine production from hCD27-Tg-derived T
      cells when combined with TCR stimulation. Administration of 1F5 to hCD27-Tg mice
      enhanced Ag-specific CD8(+) T cell responses to protein vaccination comparably to
      an agonist anti-mCD27 mAb. In syngeneic mouse tumor models, 1F5 showed potent
      antitumor efficacy and induction of protective immunity, which was dependent on
      CD4(+) and CD8(+) T cells. The requirement of FcR engagement for the agonistic
      and antitumor activities of 1F5 was demonstrated using an aglycosylated version
      of the 1F5 mAb. These data with regard to the targeting of hCD27 are consistent
      with previous reports on targeting mCD27 and provide a rationale for the clinical
      development of the 1F5 mAb, for which studies in advanced cancer patients have
      been initiated under the name CDX-1127. 

PMID- 24026079
TI  - IL-17 promotes neutrophil entry into tumor-draining lymph nodes following
      induction of sterile inflammation.
AB  - Blood-borne neutrophils are excluded from entering lymph nodes across vascular
      portals termed high endothelial venules (HEVs) because of lack of expression of
      the CCR7 homeostatic chemokine receptor. Induction of sterile inflammation
      increases neutrophil entry into tumor-draining lymph nodes (TDLNs), which is
      critical for induction of antitumor adaptive immunity following treatments such
      as photodynamic therapy (PDT). However, the mechanisms controlling neutrophil
      entry into TDLNs remain unclear. Prior evidence that IL-17 promotes neutrophil
      emigration to sites of infection via induction of CXCL2 and CXCL1 inflammatory
      chemokines raised the question of whether IL-17 contributes to chemokine
      dependent trafficking in TDLNs. In this article, we demonstrate rapid
      accumulation of IL-17-producing Th17 cells in the TDLNs following induction of
      sterile inflammation by PDT. We further report that nonhematopoietic expression
      of IL-17RA regulates neutrophil accumulation in TDLNs following induction of
      sterile inflammation by PDT. We show that HEVs are the major route of entry of
      blood-borne neutrophils into TDLNs through interactions of l-selectin with HEV
      expressed peripheral lymph node addressin and by preferential interactions
      between CXCR2 and CXCL2 but not CXCL1. CXCL2 induction in TDLNs was mapped in a
      linear pathway downstream of IL-17RA-dependent induction of IL-1beta. These
      results define a novel IL-17-dependent mechanism promoting neutrophil delivery
      across HEVs in TDLNs during acute inflammatory responses. 

PMID- 24026081
TI  - Human T cells engineered to express a programmed death 1/28 costimulatory
      retargeting molecule display enhanced antitumor activity.
AB  - Adoptive transfer of T cells genetically modified to express cancer-specific
      receptors can mediate impressive tumor regression in terminally ill patients.
      However, T cell function and persistence over time could be hampered by the
      activation of inhibitory costimulatory pathways, such as programmed death 1
      (PD1)/programmed death ligand 1, leading to T cell exhaustion and providing tumor
      cells with an escape mechanism from immunosurveillance. In addition, the lack of
      positive costimulation at the tumor site can further dampen T cell response.
      Thus, as T cell genetic engineering has become clinically relevant, we aimed at
      enhancing T cell antitumor activity by genetically diverting T cell-negative
      costimulatory signals into positive ones using chimeric costimulatory retargeting
      molecules and which are composed of the PD1 extracellular domain fused to the
      signaling domains of positive costimulatory molecules such as CD28 and 4-1BB.
      After characterizing the optimal PD1 chimera, we designed and optimized a
      tripartite retroviral vector that enables the simultaneous expression of this
      chimeric molecule in conjunction with a cancer-specific TCR. Human T cells,
      transduced to express a PD1/28 chimeric molecule, exhibited enhanced cytokine
      secretion and upregulation of activation markers upon coculture with tumor cells.
      These engineered cells also proliferated better compared with control cells.
      Finally, we tested the function of these cells in two xenograft models of human
      melanoma tumors and show that PD1/28-engineered human T cells demonstrated
      superior antitumor function. Overall, we propose that engineering T cells with a
      costimulatory retargeting molecule can enhance their function, which bears
      important implications for the improvement of T cell immunotherapy. 

PMID- 24026080
TI  - CD8+ memory T cells appear exhausted within hours of acute virus infection.
AB  - CD8(+) memory T cells are abundant and are activated in a near-synchronous manner
      by infection, thereby providing a unique opportunity to evaluate the coordinate
      functional and phenotypic changes that occur in vivo within hours of viral
      challenge. Using two disparate virus challenges of mice, we show that splenic
      CD8(+) memory T cells rapidly produced IFN-gamma in vivo; however, within 18-24
      h, IFN-gamma synthesis was terminated and remained undetectable for >= 48 h. A
      similar on/off response was observed in CD8(+) memory T cells in the peritoneal
      cavity. Cessation of IFN-gamma production in vivo occurred despite the continued
      presence of immunostimulatory viral Ag, indicating that the initial IFN-gamma
      response had been actively downregulated and that the cells had been rendered
      refractory to subsequent in vivo Ag contact. Downregulation of IFN-gamma
      synthesis was accompanied by the upregulation of inhibitory receptor expression
      on the T cells, and ex vivo analyses using synthetic peptides revealed a
      concurrent hierarchical loss of cytokine responsiveness (IL-2, then TNF, then IFN
      gamma) taking place during the first 24 h following Ag contact. Thus, within
      hours of virus challenge, CD8(+) memory T cells display the standard hallmarks of
      T cell exhaustion, a phenotype that previously was associated only with chronic
      diseases and that is generally viewed as a gradually developing and pathological
      change in T cell function. Our data suggest that, instead, the "exhaustion"
      phenotype is a rapid and normal physiological T cell response.

PMID- 24026082
TI  - Immunotherapy targeting inhibitory Fcgamma receptor IIB (CD32b) in the mouse is
      limited by monoclonal antibody consumption and receptor internalization.
AB  - Genetic deficiency of the inhibitory Fc receptor, FcgammaRIIB (CD32b), has been
      shown to augment the activity of activatory FcgammaR and promote mAb
      immunotherapy. To investigate whether mAbs capable of blocking FcgammaRIIB have
      similar capacity, we recently generated a panel of specific anti-mouse
      FcgammaRIIB mAbs that do not cross-react with other FcRs, allowing us to study
      the potential of FcgammaRIIB as a therapeutic target. Previous work revealed a
      number of these mAbs capable of eliciting programmed cell death of targets, and
      in the present study we demonstrated their ability to promote target cell
      phagocytosis. However, in a variety of murine tumor models, anti-FcgammaRIIB mAbs
      demonstrated limited therapeutic activity despite optimized treatment regimens.
      Unexpectedly, we observed that the anti-FcgammaRIIB mAbs are rapidly and
      extensively consumed in vivo, both by the tumor and host cells, including B
      cells, leading to a precipitous loss from the circulation. Closer analysis
      revealed that the anti-FcgammaRIIB mAbs become extensively internalized from the
      cell surface within 24 h in vivo, likely explaining their suboptimal efficacy.
      Subsequent studies revealed that anti-FcgammaRIIB mAb immunotherapy was effective
      when used against FcgammaRIIB(+) tumors in FcgammaRIIB(-/-) recipients,
      indicating that consumption of the mAb by nontumor cells is the primary
      limitation of these reagents. Importantly, similar rates of internalization were
      not seen on human target cells, at least in vitro. These studies further
      highlight the need to determine the propensity of mAb therapeutics to internalize
      target receptors and also identify potential key differences between human and
      mouse cells in this respect. 

PMID- 24026083
TI  - Authors' response to Almirall et al.

PMID- 24026085
TI  - Longitudinal bracketed epiphysis of proximal phalanx of the great toe with
      congenital hallux varus managed simultaneously with monorail external fixator: a
      case report.
AB  - Longitudinal bracketed epiphysis (delta phalanx) is a rare congenital anomaly
      that affects phalanges in the hand more commonly than toes. We present a rare
      case of congenital hallux varus with longitudinal bracketed epiphysis of proximal
      phalanx with bifid distal phalanx of the great toe, which was managed with
      monorail type of external fixator. To the best of our knowledge, this is the
      first report of its successful implementation in simultaneous treatment of
      longitudinal bracketed epiphysis of the proximal phalanx of the great toe and
      hallux varus. Apart from adding to the literature a case of rare subtype of delta
      phalanx with hallux varus, the present study highlights the role of a reliable
      alternative in its management.

PMID- 24026086
TI  - Revision MTP arthrodesis for failed MTP arthroplasty.
AB  - INTRODUCTION: Although the gold standard to address hallux rigidus that fails
      conservative treatment is an arthrodesis, some surgeons have attempted to use
      arthroplasty to improve range of motion and to simulate a normal joint. When
      these implants do fail, a salvage MTP arthrodesis is the only surgical option for
      these patients. This research aims to outline various methods to arthrodese the
      MTP joint in salvage situations. METHODS: We retrospectively looked at patients
      who underwent a first-MTP fusion after failure of an implant arthroplasty. All
      fusions involved either bone allograft or autograft and internal fixation. The
      patients were assessed clinically, radiographically, and with the Ankle Society
      Hallux Metatarsophalangeal-Interphalangeal (AOFAS MTP-IP) clinical questionnaire
      preoperatively and postoperatively. RESULTS: In all, 11 patients met the
      inclusion criteria. The average age of patients at the time of the salvage MTP
      arthrodesis was 57 years. The interval time between primary surgery and revision
      arthrodesis was on average 84.2 months. There was a high reoperation rate, with 7
      operative procedures occurring per 12 arthrodeses (58%). The average time to
      radiographic fusion was 6.9 +/- 4.8 months; 41.7% of patients had a delayed union
      (>6 months to fusion). Two patients had symptomatic nonunions (16.7%). All the
      patients had an improvement in their AOFAS MTP-IP score. CONCLUSION: Although
      salvage arthrodeses for failed arthroplasties generally have favorable
      satisfaction rates and are a powerful tool in treating this painful condition,
      they are fraught with complications. They unite slower, have a significantly
      higher reoperation rate, and have lower AOFAS scores than primary fusions.

PMID- 24026087
TI  - The unexpected with ankle fracture: traumatic tibialis posterior tendon
      dislocation: a case report and literature review.
AB  - Traumatic dislocation of tibialis posterior is infrequently reported in the
      literature. It is rare but potential cause of persistent pain that can be easily
      missed. Concomitant ankle fracture may obscure the clinical picture and if
      unsuspected, consequences such as iatrogenic injury to tibialis posterior tendon
      while fixing the medial malleolus may occur. We report our experience in the
      management of a tibialis posterior tendon dislocation associated with ankle
      fracture. A review of all English literature had been carried with a focus on
      treatment options.

PMID- 24026088
TI  - The direct plantar plate repair technique.
AB  - Lesser metatarsophalangeal (MTP) joint instability is a common and painful
      condition that can severely limit activity and recreation. Synovitis and joint
      effusion may be seen early on with progression of instability to encompass
      predislocation and eventual complete dislocation of the MTP joint. Various
      surgical techniques have been described to treat lesser MTP joint instability and
      associated hammertoe deformities. Many surgeons experience frustration with the
      surgical outcome of metatarsal osteotomies and flexor transfers commonly used for
      this condition. The plantar plate apparatus is felt to be at the heart of the
      pathomechanics of this condition in many instances and is often misunderstood or
      even overlooked. Indirect dorsal approaches to plantar plate repair often require
      reliance on complex instrumentation and provide a limited view of the involved
      structures. The authors describe a direct plantar approach technique for plantar
      plate repair with realignment of the lesser MTP joint and hammertoe pathologies.

PMID- 24026089
TI  - Hysteroscopic metroplasty: reproductive outcome in relation to septum size.
AB  - PURPOSE: Our aim is to determine if the reproductive performance after
      hysteroscopic resection of partial uterine septum was related to septum size.
      METHODS: The retrospective and comparative cohort study was conducted in a
      University-affiliated Hospital. A cohort of 112 non-parous patients was treated
      for a partial uterine septum. The septum size was evaluated by hysteroscopy and
      transvaginal 3-dimensional ultrasound. The patients were stratified into two
      groups: group 1 (85 women) with small partial uterine septum (<=2.5 cm) and group
      2 (27 women) with large partial uterine septum (>2.5 cm). They were also divided
      according to their obstetrics history: 39 infertile women and 73 aborters. All
      underwent hysteroscopic metroplasty with a resectoscope with an equatorial
      semicircular loop cutting 0 degrees  with monopolar energy. All septa were almost
      completely removed and no complications occurred. RESULTS: The two groups of
      patients with small (group 1) and large (group 2) partial uterine septum were
      compared in the terms of reproductive history and performance before and after
      surgery. In the overall population the reproductive performance after surgery is
      greatly improved. No significant differences in reproductive performance were
      evident between patients with small and large partial uterine septa. The
      reproductive performance was also similar in infertile patients and in aborters.
      CONCLUSIONS: This study demonstrates that hysteroscopic metroplasty in cases of
      partial uterine septum and infertility significantly improves the reproductive
      performance irrespectively of septum size and that reproductive performance is
      independent from previous obstetrics history.

PMID- 24026090
TI  - Should pelvic exenteration for symptomatic relief in gynaecology malignancies be
      offered?
AB  - OBJECTIVE: To review the outcomes of pelvic exenterative surgery done with a
      palliative intent and evaluate its role in relapsed gynaecology malignancies.
      METHOD: This is a retrospective cohort study between April 2009 and May 2012 in
      Oxford Gynaecological Cancer Centre. Patients were identified from the oncology
      surgical database. RESULTS: 18 patients were identified with a mean age 54 (26
      79) years, who underwent surgery for symptomatic recurrent cancer. All except one
      patient had radiotherapy prior to surgery. 12 patients had cervical cancer, five
      had vulval cancer and one had endometrial cancer. About half of the patients had
      major surgical complications; however, majority was patients satisfied with the
      outcome. CONCLUSION: Pelvic exenteration in this context carries considerable
      morbidity and in this series achieved good symptom control with a mean overall
      survival of 11 months. Careful patient selection, adequate counselling and
      ongoing support are imperative of successful outcome.

PMID- 24026091
TI  - CYP2D6 poor metabolizer status might be associated with better response to
      risperidone treatment.
AB  - The variability in the antipsychotic response is, to some extent, genetically
      determined. Several studies have attempted to establish a role for genetic
      variation in genes coding pharmacokinetic and pharmacodynamic targets, but to
      date, no definite genetic predictive marker has been identified. We aimed to
      explore the putative role of 19 genetic variants and risperidone clinical
      improvement in 76 White schizophrenic inpatients, measured as change in Positive
      and Negative Syndrome Scale (PANSS). CYP2D6 poor metabolism was significantly
      associated with greater clinical improvement in total PANSS and a trend was also
      found for MDR1 3435C>T to higher total PANSS scores in 3435T carriers. This study
      suggests the importance that genetic variability on pharmacokinetic factors may
      have in risperidone response and gives evidence for the need for further
      investigation in order to establish the actual predictive value and clinical
      utility that CYP2D6 genotyping might have in risperidone therapy management. 

PMID- 24026092
TI  - Genetic and nongenetic variation revealed for the principal components of human
      gene expression.
AB  - Principal components analysis has been employed in gene expression studies to
      correct for population substructure and batch and environmental effects. This
      method typically involves the removal of variation contained in as many as 50
      principal components (PCs), which can constitute a large proportion of total
      variation present in the data. Each PC, however, can detect many sources of
      variation, including gene expression networks and genetic variation influencing
      transcript levels. We demonstrate that PCs generated from gene expression data
      can simultaneously contain both genetic and nongenetic factors. From heritability
      estimates we show that all PCs contain a considerable portion of genetic
      variation while nongenetic artifacts such as batch effects were associated to
      varying degrees with the first 60 PCs. These PCs demonstrate an enrichment of
      biological pathways, including core immune function and metabolic pathways. The
      use of PC correction in two independent data sets resulted in a reduction in the
      number of cis- and trans-expression QTL detected. Comparisons of PC and linear
      model correction revealed that PC correction was not as efficient at removing
      known batch effects and had a higher penalty on genetic variation. Therefore,
      this study highlights the danger of eliminating biologically relevant data when
      employing PC correction in gene expression data. 

PMID- 24026093
TI  - Estimating individual admixture proportions from next generation sequencing data.
AB  - Inference of population structure and individual ancestry is important both for
      population genetics and for association studies. With next generation sequencing
      technologies it is possible to obtain genetic data for all accessible genetic
      variations in the genome. Existing methods for admixture analysis rely on known
      genotypes. However, individual genotypes cannot be inferred from low-depth
      sequencing data without introducing errors. This article presents a new method
      for inferring an individual's ancestry that takes the uncertainty introduced in
      next generation sequencing data into account. This is achieved by working
      directly with genotype likelihoods that contain all relevant information of the
      unobserved genotypes. Using simulations as well as publicly available sequencing
      data, we demonstrate that the presented method has great accuracy even for very
      low-depth data. At the same time, we demonstrate that applying existing methods
      to genotypes called from the same data can introduce severe biases. The presented
      method is implemented in the NGSadmix software available at
      http://www.popgen.dk/software. 

PMID- 24026094
TI  - Statistical properties of the site-frequency spectrum associated with lambda
      coalescents.
AB  - Statistical properties of the site-frequency spectrum associated with Lambda
      coalescents are our objects of study. In particular, we derive recursions for the
      expected value, variance, and covariance of the spectrum, extending earlier
      results of Fu (1995) for the classical Kingman coalescent. Estimating coalescent
      parameters introduced by certain Lambda-coalescents for data sets too large for
      full-likelihood methods is our focus. The recursions for the expected values we
      obtain can be used to find the parameter values that give the best fit to the
      observed frequency spectrum. The expected values are also used to approximate the
      probability a (derived) mutation arises on a branch subtending a given number of
      leaves (DNA sequences), allowing us to apply a pseudolikelihood inference to
      estimate coalescence parameters associated with certain subclasses of Lambda
      coalescents. The properties of the pseudolikelihood approach are investigated on
      simulated as well as real mtDNA data sets for the high-fecundity Atlantic cod
      (Gadus morhua). Our results for two subclasses of Lambda-coalescents show that
      one can distinguish these subclasses from the Kingman coalescent, as well as
      between the Lambda-subclasses, even for a moderate (maybe a few hundred) sample
      size. 

PMID- 24026096
TI  - Evidence for a tumor suppressor role for the large tumor suppressor genes LATS1
      and LATS2 in human cancer.
AB  - The role of Large tumor suppressor LATS/Warts in human cancer is not clearly
      understood. Here we show that hLATS1/2 cancer mutations affect their expression
      and kinase activity. hLATS1/2 mutants exhibit a decreased activity in inhibiting
      YAP and tissue growth. Therefore, hLATS1/2 alleles from human cancer can be loss
      of-function mutations. 

PMID- 24026095
TI  - Finding the factors of reduced genetic diversity on X chromosomes of Macaca
      fascicularis: male-driven evolution, demography, and natural selection.
AB  - The ratio of genetic diversity on X chromosomes relative to autosomes in
      organisms with XX/XY sex chromosomes could provide fundamental insight into the
      process of genome evolution. Here we report this ratio for 24 cynomolgus monkeys
      (Macaca fascicularis) originating in Indonesia, Malaysia, and the Philippines.
      The average X/A diversity ratios in these samples was 0.34 and 0.20 in the
      Indonesian-Malaysian and Philippine populations, respectively, considerably lower
      than the null expectation of 0.75. A Philippine population supposed to derive
      from an ancestral population by founding events showed a significantly lower
      ratio than the parental population, suggesting a demographic effect for the
      reduction. Taking sex-specific mutation rate bias and demographic effect into
      account, expected X/A diversity ratios generated by computer simulations roughly
      agreed with the observed data in the intergenic regions. In contrast, silent
      sites in genic regions on X chromosomes showed strong reduction in genetic
      diversity and the observed X/A diversity ratio in the genic regions cannot be
      explained by mutation rate bias and demography, indicating that natural selection
      also reduces the level of polymorphism near genes. Whole-genome analysis of a
      female cynomolgus monkey also supported the notion of stronger reduction of
      genetic diversity near genes on the X chromosome. 

PMID- 24026097
TI  - The Drosophila wings apart gene anchors a novel, evolutionarily conserved pathway
      of neuromuscular development.
AB  - wings apart (wap) is a recessive, semilethal gene located on the X chromosome in
      Drosophila melanogaster, which is required for normal wing-vein patterning. We
      show that the wap mutation also results in loss of the adult jump muscle. We use
      complementation mapping and gene-specific RNA interference to localize the wap
      locus to the proximal X chromosome. We identify the annotated gene CG14614 as the
      gene affected by the wap mutation, since one wap allele contains a non-sense
      mutation in CG14614, and a genomic fragment containing only CG14614 rescues the
      jump-muscle phenotypes of two wap mutant alleles. The wap gene lies centromere
      proximal to touch-insensitive larva B and centromere-distal to CG14619, which is
      tentatively assigned as the gene affected in introverted mutants. In mutant wap
      animals, founder cell precursors for the jump muscle are specified early in
      development, but are later lost. Through tissue-specific knockdowns, we
      demonstrate that wap function is required in both the musculature and the nervous
      system for normal jump-muscle formation. wap/CG14614 is homologous to vertebrate
      wdr68, DDB1 and CUL4 associated factor 7, which also are expressed in
      neuromuscular tissues. Thus, our findings provide insight into mechanisms of
      neuromuscular development in higher animals and facilitate the understanding of
      neuromuscular diseases that may result from mis-expression of muscle-specific or
      neuron-specific genes. 

PMID- 24026099
TI  - Hot regions of noninterfering crossovers coexist with a nonuniformly interfering
      pathway in Arabidopsis thaliana.
AB  - In most organisms that have been studied, crossovers formed during meiosis
      exhibit interference: nearby crossovers are rare. Here we provide an in-depth
      study of crossover interference in Arabidopsis thaliana, examining crossovers
      genome-wide in >1500 backcrosses for both male and female meiosis. This unique
      data set allows us to take a two-pathway modeling approach based on superposing a
      fraction p of noninterfering crossovers and a fraction (1 - p) of interfering
      crossovers generated using the gamma model characterized by its interference
      strength nu. Within this framework, we fit the two-pathway model to the data and
      compare crossover interference strength between chromosomes and then along
      chromosomes. We find that the interfering pathway has markedly higher
      interference strength nu in female than in male meiosis and also that male
      meiosis has a higher proportion p of noninterfering crossovers. Furthermore, we
      test for possible intrachromosomal variations of nu and p. Our conclusion is that
      there are clear differences between left and right arms as well as between
      central and peripheral regions. Finally, statistical tests unveil a genome-wide
      picture of small-scale heterogeneities, pointing to the existence of hot regions
      in the genome where crossovers form preferentially without interference. 

PMID- 24026098
TI  - Pleiotropic effects of a mitochondrial-nuclear incompatibility depend upon the
      accelerating effect of temperature in Drosophila.
AB  - Interactions between mitochondrial and nuclear gene products that underlie
      eukaryotic energy metabolism can cause the fitness effects of mutations in one
      genome to be conditional on variation in the other genome. In ectotherms, the
      effects of these interactions are likely to depend upon the thermal environment,
      because increasing temperature accelerates molecular rates. We find that
      temperature strongly modifies the pleiotropic phenotypic effects of an
      incompatible interaction between a Drosophila melanogaster polymorphism in the
      nuclear-encoded, mitochondrial tyrosyl-transfer (t)RNA synthetase and a D.
      simulans polymorphism in the mitochondrially encoded tRNA(Tyr). The incompatible
      mitochondrial-nuclear genotype extends development time, decreases larval
      survivorship, and reduces pupation height, indicative of decreased energetic
      performance. These deleterious effects are ameliorated when larvae develop at 16
      degrees  and exacerbated at warmer temperatures, leading to complete sterility in
      both sexes at 28 degrees . The incompatible genotype has a normal metabolic rate
      at 16 degrees  but a significantly elevated rate at 25 degrees , consistent with
      the hypothesis that inefficient energy metabolism extends development in this
      genotype at warmer temperatures. Furthermore, the incompatibility decreases
      metabolic plasticity of larvae developed at 16 degrees , indicating that cooler
      development temperatures do not completely mitigate the deleterious effects of
      this genetic interaction. Our results suggest that the epistatic fitness effects
      of metabolic mutations may generally be conditional on the thermal environment.
      The expression of epistatic interactions in some environments, but not others,
      weakens the efficacy of selection in removing deleterious epistatic variants from
      populations and may promote the accumulation of incompatibilities whose fitness
      effects will depend upon the environment in which hybrids occur. 

PMID- 24026100
TI  - Phylogenies of central element proteins reveal the dynamic evolutionary history
      of the mammalian synaptonemal complex: ancient and recent components.
AB  - During meiosis, the stable pairing of the homologous chromosomes is mediated by
      the assembly of the synaptonemal complex (SC). Its tripartite structure is well
      conserved in Metazoa and consists of two lateral elements (LEs) and a central
      region (CR) that in turn is formed by several transverse filaments (TFs) and a
      central element (CE). In a previous article, we have shown that not only the
      structure, but also the major structural proteins SYCP1 (TFs) and SYCP3 (LEs) of
      the mammalian SC are conserved in metazoan evolution. In continuation of this
      work, we now investigated the evolution of the mammalian CE-specific proteins
      using phylogenetic and biochemical/cytological approaches. In analogy to the
      observations made for SYCP1 and SYCP3, we did not detect homologs of the
      mammalian CE proteins in insects or nematodes, but in several other metazoan
      clades. We were able to identify homologs of three mammalian CE proteins in
      several vertebrate and invertebrate species, for two of these proteins down to
      the basal-branching phylum of Cnidaria. Our approaches indicate that the SC arose
      only once, but evolved dynamically during diversification of Metazoa. Certain
      proteins appear to be ancient in animals, but successive addition of further
      components as well as protein loss and/or replacements have also taken place in
      some lineages. 

PMID- 24026101
TI  - Analysis of allele-specific expression in mouse liver by RNA-Seq: a comparison
      with Cis-eQTL identified using genetic linkage.
AB  - We report an analysis of allele-specific expression (ASE) and parent-of-origin
      expression in adult mouse liver using next generation sequencing (RNA-Seq) of
      reciprocal crosses of heterozygous F1 mice from the parental strains C57BL/6J and
      DBA/2J. We found a 60% overlap between genes exhibiting ASE and putative cis
      acting expression quantitative trait loci (cis-eQTL) identified in an intercross
      between the same strains. We discuss the various biological and technical factors
      that contribute to the differences. We also identify genes exhibiting parental
      imprinting and complex expression patterns. Our study demonstrates the importance
      of biological replicates to limit the number of false positives with RNA-Seq
      data. 

PMID- 24026103
TI  - Quantitative analysis of diagnosing pancreatic fibrosis using EUS-elastography
      (comparison with surgical specimens).
AB  - BACKGROUND: An accurate diagnosis of pancreatic fibrosis is clinically important
      and may have potential for staging chronic pancreatitis. The aim of this study
      was to diagnose the grade of pancreatic fibrosis through a quantitative analysis
      of endoscopic ultrasound elastography (EUS-EG). METHODS: From September 2004 to
      October 2010, 58 consecutive patients examined by EUS-EG for both pancreatic
      tumors and their upstream pancreas before pancreatectomy were enrolled.
      Preoperative EUS-EG images in the upstream pancreas were statistically
      quantified, and the results were retrospectively compared with postoperative
      histological fibrosis in the same area. For the quantification of EUS-EG images,
      4 parameters (mean, standard deviation, skewness, and kurtosis) were calculated
      using novel software. Histological fibrosis was graded into 4 categories (normal,
      mild fibrosis, marked fibrosis, and severe fibrosis) according to a previously
      reported scoring system. RESULTS: The fibrosis grade in the upstream pancreas was
      normal in 24 patients, mild fibrosis in 19, marked fibrosis in 6, and severe
      fibrosis in 9. Fibrosis grade was significantly correlated with all 4
      quantification parameters (mean r = -0.75, standard deviation r = -0.54, skewness
      r = 0.69, kurtosis r = 0.67). According to the receiver operating characteristic
      analysis, the mean was the most useful parameter for diagnosing pancreatic
      fibrosis. Using the mean, the area under the ROC curves for the diagnosis of mild
      or higher-grade fibrosis, marked or higher-grade fibrosis and severe fibrosis
      were 0.90, 0.90, and 0.90, respectively. CONCLUSIONS: An accurate diagnosis of
      pancreatic fibrosis may be possible by analyzing EUS-EG images.

PMID- 24026104
TI  - Does dopamine block the spawning of the acroporid coral Acropora tenuis?
AB  - Most corals undergo spawning after a particular moon phase, but how moon-related
      spawning is endogenously regulated in corals remains unknown. The objective of
      the present study was to evaluate whether dopamine (DA) affects spawning in
      Acropora tenuis. When pieces of four A. tenuis colonies were reared under a
      natural photoperiod and water temperature, spawning was observed after the
      predicted moon phase. After exposure to water containing DA at 0.1 MUM, pieces of
      the same colonies only released 5 to 10 bundles. Co-treatment with DA and
      pimozide (D1 and D2 receptors antagonist), but not domperidone (D2 receptor
      antagonist), induced mass release of bundles from the colonies. A cross
      experiment revealed high fertilization rates between the control colonies (95%)
      and between the control and DA-treated colonies (90%), suggesting that gametes
      developed normally in coral tissue. Therefore, DA appears to have an inhibitory
      effect on the spawning of A. tenuis. 

PMID- 24026105
TI  - Downregulation of miR-145 contributes to lung adenocarcinoma cell growth to form
      brain metastases.
AB  - The development of metastases involves the dissociation of cells from the primary
      tumor, penetrating the basement membrane, invasion and exiting from the
      vasculature to seed, and finally colonizing in distant tissues. The formation of
      brain metastasis (BM) in lung adenocarcinoma remains poorly understood. We
      examined the differential microRNA (miRNA) expression profiles of 5 primary and 3
      brain metastatic lung adenocarcinoma samples by Agilent miRNA Microarrays. Five
      upregulated miRNAs (miRs-9*, -1471, 718, 3656, 720) and 3 downregulated miRNAs
      (miRs-214, -145 and -23a) were detected. The 4 most significantly deregulated
      miRNAs (miR-145, miR-214, miR-9* and miR-1471) were validated in the additional
      43 samples (35 primary and 8 brain metastatic lung adenocarcinoma samples) using
      TaqMan quantitative PCR. By functional assay, we found that the expression of miR
      145 can regulate the ability of proliferation of A549 and SPC-A1 cells in vitro,
      but is not related to lymph node metastasis, migration and invasion. These
      results suggest that miR-145 may have a cell type-specific function and play
      important roles in the process of BM from lung adenocarcinoma. 

PMID- 24026106
TI  - Tongue coating microbiome regulates the changes in tongue texture and coating in
      patients with post-menopausal osteoporosis of Gan-shen deficiency syndrome type.
AB  - Tongue inspection is a unique and important method of diagnosis in traditional
      Chinese medicine (TCM). It is a diagnostic approach which involves observing the
      changes in the tongue proper and tongue coating in order to understand the
      physiological functions and pathological changes of the body. However, the
      biological basis of TCM tongue diagnosis remains to be poorly understood and
      lacks systematic investigation at the molecular level. In this study, we
      evaluated the effects of tongue coating microbiome on changes in the tongue
      texture and coating in patients with post-menopausal osteoporosis (PMO) of Gan
      shen deficiency syndrome type. Our aim was to delineate the mechanisms of tongue
      coating microbiome-induced changes in the tongue texture and coating by
      investigating the histomorphological changes and performing a bacterial analysis
      of the tongue coating. We found that the number of intermediate cells in the red
      tongue with a thin coating was higher, while the number of superficial cells in
      the red tongue with a thin coating was lower. The maturation value (MV) of tongue
      exfoliated cells in the red tongue with a thin coating decreased, compared with
      that in the pale red tongue with a thin white coating. Furthermore, the total
      bacterial count, oral streptococcus, Gram-positive (G+) and Gram-negative (G-)
      anaerobic bacteria in the red tongue with a thin coating was significantly
      decreased compared with the pale red tongue with a thin white coating. The
      results of ultrastructural examination demonstrated that the number of epithelial
      cells and bacteria in the red tongue with a thin coating decreased compared with
      that in the pale red tongue with a thin white coating. These observations
      indicate that the tongue coating microbiome may be an important factor
      contributing to changes in the tongue in patients with PMO of Gan-shen deficiency
      syndrome type.

PMID- 24026107
TI  - The energy intake modulates the association of the -55CT polymorphism of UCP3
      with body weight in type 2 diabetic patients.
AB  - BACKGROUND: Previous association studies of the -55CT polymorphism of the
      uncoupling protein 3 (UCP3) gene with body mass index (BMI) have provided
      inconsistent results. The study aim is twofold: (1) to evaluate the association
      of the -55CT polymorphism of UCP3 with BMI in two independent populations to
      verify the reproducibility of the finding; (2) to evaluate whether this
      association is modulated by energy intake. METHODS: Study participants are 736
      males and females with type 2 diabetes belonging to independent populations
      (N=394 population 1; N=342 population 2). Anthropometry and laboratory parameters
      were measured; in population 2, energy intake and physical exercise were also
      assessed. RESULTS: The -55CT polymorphism was associated with a significantly
      lower BMI in population 1 (27.8+/-3.9 vs 28.9+/-4.6 kg m(-2); P<0.02), the
      finding was confirmed in population 2 (that is, 30.3+/-6.0 vs 32.1+/-5.9 kg m(
      2); P<0.01) independent of gender, age, HbA1c, use of drugs and energy intake. To
      evaluate the role of diet in population 2, the study participants were stratified
      by genotype and tertiles of energy intake. In both genotype groups, BMI increased
      with increasing caloric intake with a significant trend (P<0.001), the BMI
      difference between the two genotype groups was large and statistically
      significant in the lower tertile (27.6 vs 31.2 kg m(-2); P<0.001), intermediate
      in the second tertile and negligible in the upper tertile (32.8 vs 32.9; kg m(
      2); nonsignificant). The multivariate regression analysis confirmed a significant
      interaction between genotype and energy intake as correlates of BMI independent
      of age, gender, glucose control, physical activity and medications for diabetes
      (P=0.004). CONCLUSIONS: The study replicates in two independent populations the
      association between the -55CT polymorphism of UCP3 and a lower BMI. This
      association was modulated by energy intake, thus suggesting that the unmeasured
      effect of diet may partly account for inconsistencies of prior association
      studies.

PMID- 24026108
TI  - Serum ischaemia-modified albumin level is an irrelevant predictive factor for
      ischaemic duration in mesenteric ischaemia.
AB  - BACKGROUND: Acute mesenteric ischaemia is an emergency condition that requires
      urgent and expeditious diagnosis and immediate surgical or medical intervention.
      The initial hours are critical for the recovery of the affected bowel segment.
      Thus, its clinic diagnostic biomarkers are important when it comes to reducing
      mortality and morbidity rates. METHODS: Twenty-four male Sprague-Dawley rats were
      included in the study. The rats were divided into three equal groups. Those in
      Group I were sacrificed to determine the basal serum values of ischaemia-modified
      albumin (IMA) after a simple laparotomy. The superior mesenteric artery (SMA) was
      clamped in a simple laparotomy in Groups II and III; blood samples were taken at
      120 minutes in Group II and 360 minutes in Group III. The serum IMA levels were
      identified from the blood samples and the results obtained were compared
      statistically. RESULTS: The serum IMA levels were determined to be 22+/-6 (22)
      MU/L, 34+/-7 (34) MU/L and 36+/-4 (37) MU/L in Groups I, II and III,
      respectively. The differences between the groups were not statistically
      significant. CONCLUSION: Our results showed that the serum IMA level is not an
      appropriate biomarker for acute mesenteric ischaemia. Additionally, the IMA level
      is not an appropriate biomarker for the detection of ischaemia duration. However,
      future studies should be conducted to clarify the efficacy of serum IMA levels
      under different ischaemic conditions.

PMID- 24026109
TI  - Trends over time in the relative use and associated mortality of on-pump and off
      pump coronary artery bypass grafting in the Veterans Affairs system.
AB  - IMPORTANCE: Numerous studies have compared the results of on-pump and off-pump
      coronary artery bypass grafting (CABG), but little is known about how either the
      relative use of these procedures or their associated perioperative mortality have
      changed with time. OBJECTIVE: To examine trends in off- and on-pump CABG use and
      outcomes over time. DESIGN: Retrospective analysis of data from the Veterans
      Affairs Surgical Quality Improvement Program (VASQIP). SETTING: Data were
      collected from 42 Veterans Affairs cardiac surgery centers. PARTICIPANTS: All
      Veterans Affairs patients (n = 65,097) who underwent isolated primary CABG from
      October 1997 to April 2011. INTERVENTIONS: Patients underwent either on-pump (ON)
      or off-pump (OFF) CABG. MAIN OUTCOMES AND MEASURES: The percentages of ON vs OFF
      cases as a function of time. We also evaluated trends over time in rates of
      conversion from OFF to ON CABG, perioperative mortality (30-day or in-hospital),
      and VASQIP predicted risk of mortality. RESULTS: The relative use of OFF CABG
      peaked at 24% in 2003, followed by a slow and mostly consistent decline to
      stabilize at about 19%. The conversion rate decreased with time and has stayed
      less than 3.5% since 2007 (P < .001). Perioperative mortality rates decreased
      over time for both ON and OFF CABG (P < .001) and have stayed less than 2% for
      the entire cohort since 2006. The mortality associated with converted cases was
      high regardless of the surgery year and exceeded the VASQIP predicted risk of
      mortality. CONCLUSIONS AND RELEVANCE: There has been a decline in the relative
      use of OFF CABG in the Veterans Affairs system since 2003. This trend may affect
      the training of future generations in OFF surgery and influence conversion rates
      and outcomes.

PMID- 24026110
TI  - Effect of the acceptor on the performance of dye-sensitized solar cells.
AB  - Three new phenothiazine dyes were designed and synthesized, utilizing different
      acceptor groups. Upon application to TiO2-based solar cells, the effects of
      different acceptors on the photophysical and electrochemical properties of the
      dyes and the solar cell performance are detailed. The introduction of a
      pyridinium unit or 5-carboxy-1-hexyl-2,3,3-trimethyl-indolium unit into the
      molecular frame as the acceptor instead of cyano acrylic acid can effectively
      cause a red shift in the absorption spectra. Applied to DSSCs, the devices
      sensitized by CM502 with the pyridinium unit as the acceptor show the highest
      efficiency of 7.3%. The devices fabricated with dye CM501 with cyano acrylic acid
      as the acceptor exhibited the highest Voc while for the devices sensitized by the
      dye CM503 with 5-carboxy-1-hexyl-2,3,3-trimethyl-3H-indolium unit as the
      acceptor, the Voc value was the lowest, at 494 mV. The addition of TBP in the
      electrolyte can improve the performance of DSSCs fabricated using CM501 and
      CM502, with the Voc value greatly improved but the Jsc value slightly decreased.
      However, with the addition of TBP in the electrolyte, the efficiency of the cells
      sensitized by CM503 dropped significantly (from 4.9% to 1.0% when 0.1 M TBP was
      added).

PMID- 24026111
TI  - Influence of laser light on bioimplants used in otorhinolaryngology.
AB  - In otorhinolaryngology, dermatology and reconstructive surgery biomaterials as
      implants and a variety of lasers are used. Laser light applied near to an implant
      could have the risk to damage these materials. Therefore, their resistance
      exposed to laser light is of interest. A diode laser emitting at 940 nm and a CO2
      laser were used to investigate its effects to the biomaterials Bioverit(r),
      Medpor(r) and Palacos(r), and in addition, an excised implant containing
      Medpor(r) and nasal turbinate tissue, excised and fixed in formalin. The macro-
      and microscopic changes of the material, temperature development during laser
      energy application in dependency to distance of fibre and material, time of
      exposure and applied power were investigated. Interaction of diode laser light
      with Bioverit(r) (0 mm distance, 360 s, 10 W, 3,600 J) resulted in minimal
      microscopic effects in direct contact of with the fibre. Using Medpor(r) (1 mm,
      10s, 10 W, 100 J) resulted in melting and perforation. In the case of Palacos(r)
      (0.6 mm, 10s, 10 W, 100 J), melting occurred creating a flat excavation. The
      effect to Medpor(r) in nasal turbinate (1-2 mm, 10s, 10 W, 100 J) showed tissue
      denaturation and carbonisation and creation of a hole. The interaction of the CO2
      laser with Bioverit(r) (3 cm, 0.5, 1 and 5 s, 2, 10 or 20 W) induced melting and
      discolouring resulting finally in a perforating hole. Depending on the material,
      first damage starts 10 s after an impact of 100 J (threshold value). So
      interaction between laser energy and biomaterials occurs. This should be
      carefully considered during clinical laser treatments especially nearby implants.

PMID- 24026113
TI  - Psychiatric disorders: Reining in the habenula?

PMID- 24026112
TI  - Safety and efficiency of thulium laser prostate resection for the treatment of
      benign prostatic hyperplasia in large prostates.
AB  - Thulium laser resection of the prostate-tangerine technique (TmLRP-TT) dissects
      whole prostatic lobes off the surgical capsule, similar to peeling a tangerine.
      The present study aimed to evaluate the safety and efficacy of TmLRP-TT for older
      symptomatic benign prostatic hyperplasia patients with large prostates during 18
      months of follow-up. A prospective analysis of 95 consecutive patients with large
      prostates (>80 ml) who underwent surgical treatment using TmLRP-TT was carried
      out. All patients were evaluated preoperatively and at 1, 6, 12, and 18 months
      postoperatively by the International Prostate Symptom Score (IPSS), quality of
      life (QoL), maximum urinary flow rate (Q max), postvoid residual urine volume
      (PVR), International Index of Erectile Function 5 (IIEF-5), urine analysis, and
      urine culture. Perioperative complications were recorded and graded by the
      modified Clavien classification system (CCS). Mean preoperative prostate volume
      was 106.81 +/- 24.79 ml. TmLRP-TT was successfully completed in all patients. The
      mean operative duration, catheterization time, and hospital stay were 95.36 +/-
      27.06 min, 2.25 +/- 0.9 days, and 5.39 +/- 1.18 days, respectively. The decrease
      in mean hemoglobin level was 1.23 +/- 0.72 g/dl, and that in mean serum sodium
      level was 0.71 +/- 2.56 mmol/l. Within the observation period of 18 months, the
      patients showed an improvement in IPSS (20.01 +/- 7.08 vs. 4.96 +/- 3.68), QoL
      (4.10 +/- 1.16 vs. 1.23 +/- 1.30), Q max (8.14 +/- 3.81 ml/s vs. 18.33 +/- 2.56
      ml/s) and PVR (102.70 +/- 70.64 ml vs. 20.28 +/- 30.02 ml), compared with
      baseline values (P < 0.001). IIEF-5 remained stable. Minor complications occurred
      in 10 (10.52 %) of 95 patients (Clavien grade 1, 9.47 % and grade 2, 1.05 %).
      There were no severe complications requiring reintervention (Clavien grade 3, 0 %
      and grade 4, 0 %). TmLRP-TT is a safe and effective surgical endoscopic technique
      associated with a low complication rate in large prostates as assessed during an
      18-month follow-up period. It is a promising technology, which may be considered
      as one of the alternatives to open simple prostatectomy (OP) for large prostates
      in the future.

PMID- 24026114
TI  - Neuroscientists in court.
AB  - Neuroscientific evidence is increasingly being offered in court cases.
      Consequently, the legal system needs neuroscientists to act as expert witnesses
      who can explain the limitations and interpretations of neuroscientific findings
      so that judges and jurors can make informed and appropriate inferences. The
      growing role of neuroscientists in court means that neuroscientists should be
      aware of important differences between the scientific and legal fields, and,
      especially, how scientific facts can be easily misunderstood by non-scientists,
      including judges and jurors.

PMID- 24026115
TI  - Neural circuits: To stay, or to go?

PMID- 24026116
TI  - Stem cells: Small but beautiful.

PMID- 24026117
TI  - APC2 and Axin promote mitotic fidelity by facilitating centrosome separation and
      cytoskeletal regulation.
AB  - To ensure the accurate transmission of genetic material, chromosome segregation
      must occur with extremely high fidelity. Segregation errors lead to chromosomal
      instability (CIN), with deleterious consequences. Mutations in the tumor
      suppressor adenomatous polyposis coli (APC) initiate most colon cancers and have
      also been suggested to promote disease progression through increased CIN, but the
      mechanistic role of APC in preventing CIN remains controversial. Using fly
      embryos as a model, we investigated the role of APC proteins in CIN. Our findings
      suggest that APC2 loss leads to increased rates of chromosome segregation error.
      This occurs through a cascade of events beginning with incomplete centrosome
      separation leading to failure to inhibit formation of ectopic cleavage furrows,
      which result in mitotic defects and DNA damage. We test several hypotheses
      related to the mechanism of action of APC2, revealing that APC2 functions at the
      embryonic cortex with several protein partners, including Axin, to promote
      mitotic fidelity. Our in vivo data demonstrate that APC2 protects genome
      stability by modulating mitotic fidelity through regulation of the cytoskeleton. 

PMID- 24026119
TI  - Insulin and Target of rapamycin signaling orchestrate the development of ovarian
      niche-stem cell units in Drosophila.
AB  - Tissue-specific stem cells and their niches are organized into functional units
      that respond to external cues in order to maintain organ homeostasis. Insulin and
      Target of rapamycin (Tor) signaling mediate external cues that control adult
      niches and stem cells. Whether these pathways play a role in the establishment of
      niche-stem cell units during organogenesis has been little explored. We show that
      during larval development both Insulin-like receptor (InR) and Tor participate in
      the establishment of ovarian niches and germline stem cells (GSCs) in Drosophila
      melanogaster. Tor and InR are required cell-autonomously for the proliferation of
      precursors for both somatic niches and GSCs. These pathways also promote the
      formation of terminal filaments (part of the somatic niche). Significantly, InR,
      but not Tor, signaling non-autonomously promotes primordial germ cell (PGC)
      differentiation. Somatic attenuation of the pathway retards PGC differentiation,
      whereas its activation results in their precocious differentiation. We also show
      that InR-mediated PGC differentiation is independent of somatic ecdysone
      signaling, but that further differentiation into cysts requires an ecdysone
      input. These results demonstrate that Tor and InR signaling actively participate
      in the formation of ovarian niches and stem cells by affecting both cell numbers
      and differentiation. The dual influence of Tor and InR on both somatic cells and
      PGCs ensures that these two cell populations develop coordinately. Our work
      further identifies a novel step in the regulation of germ cell differentiation by
      demonstrating that following bag of marbles expression, cyst formation requires
      an additional hormonal input. 

PMID- 24026118
TI  - Wnt/beta-catenin signaling directs the regional expansion of first and second
      heart field-derived ventricular cardiomyocytes.
AB  - In mammals, cardiac development proceeds from the formation of the linear heart
      tube, through complex looping and septation, all the while increasing in mass to
      provide the oxygen delivery demands of embryonic growth. The developing heart
      must orchestrate regional differences in cardiomyocyte proliferation to control
      cardiac morphogenesis. During ventricular wall formation, the compact myocardium
      proliferates more vigorously than the trabecular myocardium, but the mechanisms
      controlling such regional differences among cardiomyocyte populations are not
      understood. Control of definitive cardiomyocyte proliferation is of great
      importance for application to regenerative cell-based therapies. We have used
      murine and human pluripotent stem cell systems to demonstrate that, during in
      vitro cellular differentiation, early ventricular cardiac myocytes display a
      robust proliferative response to beta-catenin-mediated signaling and conversely
      accelerate differentiation in response to inhibition of this pathway. Using gain-
      and loss-of-function murine genetic models, we show that beta-catenin controls
      ventricular myocyte proliferation during development and the perinatal period. We
      further demonstrate that the differential activation of the Wnt/beta-catenin
      signaling pathway accounts for the observed differences in the proliferation
      rates of the compact versus the trabecular myocardium during normal cardiac
      development. Collectively, these results provide a mechanistic explanation for
      the differences in localized proliferation rates of cardiac myocytes and point to
      a practical method for the generation of the large numbers of stem cell-derived
      cardiac myocytes necessary for clinical applications. 

PMID- 24026121
TI  - Growth factor-mediated mesodermal cell guidance and skeletogenesis during sea
      urchin gastrulation.
AB  - Growth factor signaling pathways provide essential cues to mesoderm cells during
      gastrulation in many metazoans. Recent studies have implicated the VEGF and FGF
      pathways in providing guidance and differentiation cues to primary mesenchyme
      cells (PMCs) during sea urchin gastrulation, although the relative contributions
      of these pathways and the cell behaviors they regulate are not fully understood.
      Here, we show that FGF and VEGF ligands are expressed in distinct domains in the
      embryonic ectoderm of Lytechinus variegatus. We find that PMC guidance is
      specifically disrupted in Lv-vegf3 morphants and these embryos fail to form
      skeletal elements. By contrast, PMC migration is unaffected in Lv-fgfa morphants,
      and well-patterned but shortened skeletal elements form. We use a VEGFR
      inhibitor, axitinib, to show that VEGF signaling is essential not only for the
      initial phase of PMC migration (subequatorial ring formation), but also for the
      second phase (migration towards the animal pole). VEGF signaling is not required,
      however, for PMC fusion. Inhibition of VEGF signaling after the completion of PMC
      migration causes significant defects in skeletogenesis, selectively blocking the
      elongation of skeletal rods that support the larval arms, but not rods that form
      in the dorsal region of the embryo. Nanostring nCounter analysis of ~100 genes in
      the PMC gene regulatory network shows a decrease in the expression of many genes
      with proven or predicted roles in biomineralization in vegf3 morphants. Our
      studies lead to a better understanding of the roles played by growth factors in
      sea urchin gastrulation and skeletogenesis. 

PMID- 24026120
TI  - EphA2 and Src regulate equatorial cell morphogenesis during lens development.
AB  - High refractive index and transparency of the eye lens require uniformly shaped
      and precisely aligned lens fiber cells. During lens development, equatorial
      epithelial cells undergo cell-to-cell alignment to form meridional rows of
      hexagonal cells. The mechanism that controls this morphogenesis from randomly
      packed cuboidal epithelial cells to highly organized hexagonal fiber cells
      remains unknown. In Epha2(-/-) mouse lenses, equatorial epithelial cells fail to
      form precisely aligned meridional rows; moreover, the lens fulcrum, where the
      apical tips of elongating epithelial cells constrict to form an anchor point
      before fiber cell differentiation and elongation at the equator, is disrupted.
      Phosphorylated Src-Y424 and cortactin-Y466, actin and EphA2 cluster at the
      vertices of wild-type hexagonal epithelial cells in organized meridional rows.
      However, phosphorylated Src and phosphorylated cortactin are not detected in
      disorganized Epha2(-/-) cells with altered F-actin distribution. E-cadherin
      junctions, which are normally located at the basal-lateral ends of equatorial
      epithelial cells and are diminished in newly differentiating fiber cells, become
      widely distributed in the apical, lateral and basal sides of epithelial cells and
      persist in differentiating fiber cells in Epha2(-/-) lenses. Src(-/-) equatorial
      epithelial cells also fail to form precisely aligned meridional rows and lens
      fulcrum. These results indicate that EphA2/Src signaling is essential for the
      formation of the lens fulcrum. EphA2 also regulates Src/cortactin/F-actin
      complexes at the vertices of hexagonal equatorial cells for cell-to-cell
      alignment. This mechanistic information explains how EphA2 mutations lead to
      disorganized lens cells that subsequently contribute to altered refractive index
      and cataracts in humans and mice. 

PMID- 24026122
TI  - Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate
      territories during forebrain morphogenesis.
AB  - During forebrain morphogenesis, there is extensive reorganisation of the cells
      destined to form the eyes, telencephalon and diencephalon. Little is known about
      the molecular mechanisms that regulate region-specific behaviours and that
      maintain the coherence of cell populations undergoing specific morphogenetic
      processes. In this study, we show that the activity of the Eph/Ephrin signalling
      pathway maintains segregation between the prospective eyes and adjacent regions
      of the anterior neural plate during the early stages of forebrain morphogenesis
      in zebrafish. Several Ephrins and Ephs are expressed in complementary domains in
      the prospective forebrain and combinatorial abrogation of their activity results
      in incomplete segregation of the eyes and telencephalon and in defective
      evagination of the optic vesicles. Conversely, expression of exogenous Ephs or
      Ephrins in regions of the prospective forebrain where they are not usually
      expressed changes the adhesion properties of the cells, resulting in segregation
      to the wrong domain without changing their regional fate. The failure of eye
      morphogenesis in rx3 mutants is accompanied by a loss of complementary expression
      of Ephs and Ephrins, suggesting that this pathway is activated downstream of the
      regional fate specification machinery to establish boundaries between domains
      undergoing different programmes of morphogenesis. 

PMID- 24026123
TI  - Nkx genes are essential for maintenance of ventricular identity.
AB  - Establishment of specific characteristics of each embryonic cardiac chamber is
      crucial for development of a fully functional adult heart. Despite the importance
      of defining and maintaining unique features in ventricular and atrial
      cardiomyocytes, the regulatory mechanisms guiding these processes are poorly
      understood. Here, we show that the homeodomain transcription factors Nkx2.5 and
      Nkx2.7 are necessary to sustain ventricular chamber attributes through repression
      of atrial chamber identity. Mutation of nkx2.5 in zebrafish yields embryos with
      diminutive ventricular and bulbous atrial chambers. These chamber deformities
      emerge gradually during development, with a severe collapse in the number of
      ventricular cardiomyocytes and an accumulation of excess atrial cardiomyocytes as
      the heart matures. Removal of nkx2.7 function from nkx2.5 mutants exacerbates the
      loss of ventricular cells and the gain of atrial cells. Moreover, in these Nkx
      deficient embryos, expression of vmhc, a ventricular gene, fades, whereas
      expression of amhc, an atrial gene, expands. Cell-labeling experiments suggest
      that ventricular cardiomyocytes can transform into atrial cardiomyocytes in the
      absence of Nkx gene function. Through suggestion of transdifferentiation from
      ventricular to atrial fate, our data reveal a pivotal role for Nkx genes in
      maintaining ventricular identity and highlight remarkable plasticity in
      differentiated myocardium. Thus, our results are relevant to the etiologies of
      fetal and neonatal cardiac pathology and could direct future innovations in
      cardiac regenerative medicine. 

PMID- 24026124
TI  - Coco regulates dorsoventral specification of germ layers via inhibition of
      TGFbeta signalling.
AB  - One of the earliest steps in embryonic development is the specification of the
      germ layers, the subdivision of the blastula embryo into endoderm, mesoderm and
      ectoderm. Maternally expressed members of the Transforming Growth Factor beta
      (TGFbeta) family influence all three germ layers; the ligands are required to
      induce endoderm and mesoderm, whereas inhibitors are required for formation of
      the ectoderm. Here, we demonstrate a vital role for maternal Coco, a secreted
      antagonist of TGFbeta signalling, in this process. We show that Coco is required
      to prevent Activin and Nodal signals in the dorsal marginal side of the embryo
      from invading the prospective ectoderm, thereby restricting endoderm- and
      mesoderm-inducing signals to the vegetal and marginal zones of the pre-gastrula
      Xenopus laevis embryo. 

PMID- 24026125
TI  - Gprk2 adjusts Fog signaling to organize cell movements in Drosophila
      gastrulation.
AB  - Gastrulation of Drosophila melanogaster proceeds through sequential cell
      movements: ventral mesodermal (VM) cells are induced by secreted Fog protein to
      constrict their apical surfaces to form the ventral furrow, and subsequently
      lateral mesodermal (LM) cells involute toward the furrow. How these cell
      movements are organized remains elusive. Here, we observed that LM cells extended
      apical protrusions and then underwent accelerated involution movement, confirming
      that VM and LM cells display distinct cell morphologies and movements. In a
      mutant for the GPCR kinase Gprk2, apical constriction was expanded to all
      mesodermal cells and the involution movement was abolished. In addition, the
      mesodermal cells halted apical constriction prematurely in accordance with the
      aberrant accumulation of Myosin II. Epistasis analyses revealed that the Gprk2
      mutant phenotypes were dependent on the fog gene. Overexpression of Gprk2
      suppressed the effects of excess Cta, a downstream component of Fog signaling.
      Based on these findings, we propose that Gprk2 attenuates and tunes Fog-Cta
      signaling to prevent apical constriction in LM cells and to support appropriate
      apical constriction in VM cells. Thus, the two distinct cell movements in
      mesoderm invagination are not predetermined, but rather are organized by the
      adjustment of cell signaling. 

PMID- 24026126
TI  - midlife crisis encodes a conserved zinc-finger protein required to maintain
      neuronal differentiation in Drosophila.
AB  - Stem cells generate progeny that undergo terminal differentiation. The initiation
      and maintenance of the differentiated status is crucial for tissue development,
      function and homeostasis. Drosophila neural stem cells (neuroblasts) are a model
      for stem cell self-renewal and differentiation; they divide asymmetrically to
      self-renew and generate the neurons and glia of the CNS. Here we report the
      identification of midlife crisis (mdlc; CG4973) as a gene required for the
      maintenance of neuronal differentiation and for neuroblast proliferation in
      Drosophila. mdlc encodes a ubiquitously expressed zinc-finger-containing protein
      with conserved orthologs from yeast to humans that are reported to have a role in
      RNA splicing. Using clonal analysis, we demonstrate that mdlc mutant neurons
      initiate but fail to complete differentiation, as judged by the loss of the pro
      differentiation transcription factor Prospero, followed by derepression of the
      neuroblast factors Deadpan, Asense and Cyclin E. RNA-seq shows that loss of Mdlc
      decreases pros transcript levels and results in aberrant pros splicing.
      Importantly, misexpression of the full-length human ortholog, RNF113A, completely
      rescues all CNS defects in mdlc mutants. We conclude that Mdlc plays an essential
      role in maintaining neuronal differentiation, raising the possibility that
      RNF113A regulates neuronal differentiation in the human CNS. 

PMID- 24026127
TI  - [Impact benzodiazepine dependence on the use of health services: senior' health
      study].
AB  - CONTEXT: Prolonged use of benzodiazepines increases the risk of addiction. The
      impact of this disease on the use of health services by older adults is not
      known. OBJECTIVE: Examine the association between benzodiazepine dependence and
      use of health services by older adults in Quebec. Methodology. The data comes
      from a survey conducted in Quebec in 2005-2006 with a representative sample of
      707 elderly benzodiazepine consumption in the community. Benzodiazepine
      dependence was defined according to the criteria of the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Revised Edition. The use of health
      services as measured by the incidence of consultations with health professionals
      over a period of 12 months. RESULTS: Seniors have consumed an average daily dose
      of 6.1 (+/- 7.6) mg diazepam equivalent to an average of 205 (+/- 130) days. The
      prevalence of benzodiazepine dependence has been estimated at 9.5%. This
      dependence increases the likelihood of consulting a specialist (odds ratio (OR) =
      3.42; confidence interval 95% (CI 95%) = 1.38 to 8.50). Visits to other health
      professionals frontline were not significant. CONCLUSION: The results of this
      study suggest that the proportion of seniors who become addicted to
      benzodiazepines and do not use health services for this condition is important.
      There is a need to develop programs to improve the quality of benzodiazepine use
      in this population.

PMID- 24026128
TI  - [Validity of cardiovascular prescriptions to the guidelines in the elderly
      according to the STOPP and START method].
AB  - Cardiovascular diseases are the first cause of death in elderly patients. So it
      seems important to estimate the adequacy of the medical prescriptions to the
      guidelines in this population and for these diseases. A retrospective analysis
      was performed in nine hospitals on 736 patients aged 65 years old and over
      hospitalized in the acute care geriatric unit. Cardiovascular prescribing were
      analyzed for each patient according to STOPP and START. The population (n=736)
      has a mean age of 86.7 years and belongs in 45.0% of the cases to the group of
      dependence GIR3-4. According to STOPP, two inappropriate prescriptions are
      noticed: calcium channel blockers with chronic constipation concerning 9% of the
      included population and aspirin at dose > 150 mg/day representing 8.4% of this
      population. According to START, angiotensin converting enzyme inhibitor are under
      prescribed in elderly patients with heart failure (140 patients = 19.0% of the
      population) and following acute myocardial infarction (116 patients = 15.8%).
      Anticoagulation in patients with atrial fibrillation is also under-prescribed: 82
      patients are concerned (11.0% of the population). The prescription of ACE
      inhibitor is influenced by renal insufficency in patients with heart failure. The
      anticoagulation in atrial fibrillation is age and dependence-related. This
      analysis demonstrates an inadequacy between the clinical practice and guidelines
      for two major cardiovascular diseases: the heart failure and the atrial
      fibrillation. The importance of the inadequacy was suspected of opportunities for
      improvement, in particular in the presence of their risk factors: very elderly
      patients, loss of autonomy and renal insufficiency.

PMID- 24026129
TI  - [Active management of patients with Alzheimer disease].

PMID- 24026131
TI  - [Alzheimer's disease and olfaction].
AB  - Although olfactory disorders are not at the forefront of the clinical description
      of Alzheimer's disease (AD), they are common and often overlooked by clinicians
      and by patients who are largely unaware of their deficits. The past 30 years, the
      literature has shown early olfactory deficits in AD that is spreading across the
      olfactory spectrum with disease worsening. Partial overlap between brain areas
      implies both in olfaction and AD - especially limbic system - motivating these
      researches. This study describes olfactory parameters and tests using to
      investigate peripheral (odor threshold) and central (hedonicity, familiarity,
      intensity, discrimination, identification, olfactory memory) levels. Besides,
      this article takes an inventory of olfactory disorders in AD including odor
      threshold, discrimination, identification and olfactory memory capacities with
      controversial results observed in literature. At last, we discuss which type of
      olfactory dysfunction could have a clinical interest. 

PMID- 24026132
TI  - [Non-motor symptoms in Parkinson's disease: cognition and behavior].
AB  - Although the diagnosis of Parkinson disease is based on motor symptoms, it is now
      well known that non-motor symptoms are an integral part of this pathology,
      involving in fact multiple systems. These non-motor symptoms affect large
      population of patients and can appear sometimes before the motor disorders. The
      non-motor symptoms include mainly neuropsychological difficulties,
      neuropsychiatric symptoms, and autonomic disorders, but involve also pain and
      sleep disturbances for example. Depression may occur at any stage of the disease,
      and consists in major depressive disorder, minor depressive disorder, and
      dysthymia. During the course of the disease, 50% of patients experience anxiety.
      Apathy is present in up to 30-40% of patients, due to loss of motivation,
      appearing in emotional, intellectual and behavioral domains. Dopamine
      dysregulation syndrome and impulse control disorders are not rare, and in
      relation with dopaminergic therapies. Impulse control disorders include
      pathological gambling, hyper sexuality, compulsive shopping, and eating disorder.
      Visual hallucinations can occur in 30% of patients, mostly induced by
      dopaminergic therapies. Often, they have deeper impact on the quality of life
      than the motor symptoms themselves, which stay the focus of attention during
      consulting. Identifying those can help in providing better care with a positive
      impact on the quality of life of the patients. 

PMID- 24026130
TI  - [Main interventions for rehabilitation of autobiographical memory in Alzheimer's
      disease from early to severe stage: a review and new perspectives].
AB  - Given the limitations of pharmacological treatments in Alzheimer's disease, many
      non-drug therapies have emerged in recent decades and are often offered in
      complement of pharmacological treatments. The cognitive rehabilitation
      interventions focused on memory are usual in Alzheimer's disease. Memory deficits
      are prominent from the early stages of the disease and cause detriment to patient
      autonomy in daily life. In particular, problems of identity and autobiographical
      memory, although still often overlooked in the patients' general
      neuropsychological profile, appear right away. Because of their more insidious
      negative influence, specific treatments are still underdeveloped. Rehabilitation
      of autobiographical memory is complex because it requires taking into account its
      multiple components, both semantic and episodic, but also understanding its links
      with personal identity. Thus, this article provides an overview of existing
      cognitive rehabilitation interventions of anterograde and retrograde
      autobiographical memory in Alzheimer's disease. We specify the contribution of
      new technologies to improve the consolidation of recent events memory and of a
      rehabilitation program of autobiographical memory - REMau -, derived from the
      TEMPau task, which takes into account the constructive nature of episodic
      memories via the personal semantic through different periods of life. The main
      aim is to examine what are the objectives, benefits and limitations of these
      interventions and to estimate how they can meet the more general problem of
      deficiency in personal identity. As identity is constructed on the basis of past
      experience, but is modulated by new experiences, our current challenge is to
      associate combined treatments of anterograde and retrograde memory based on the
      interaction between autobiographical memory and the self. 

PMID- 24026133
TI  - [Medical drug abuse and aging].
AB  - Drug addiction is often underestimated among the aged. Opiate drugs (mostly pain
      killers) are the most frequently implicated in drug addiction after
      benzodiazepines (BZD) in the aged. The subjects aged of 65 years or more are the
      most represented among the BZD users in France. Frequency of BZD use varies
      according to various studies from 39 to 55% in this age group. Leading a lonely
      life is associated with the use of psychotropic drugs among retired people
      (OR=1.7). Vulnerability at this age must take into account not only
      polypathology, but also the faster aging of a minority of the population under
      opiate drugs substitution treatment (OST), more subjects to drugs interaction.
      Drug addiction among elderly often reflects the drift of "lawful" doctor's
      instructions that leads to an increase in drugs use. The difficulty has to do
      with a lack of specificity of diagnosis of addiction at this age, but perhaps
      also with physicans'instructions in the aged. Some authors suggest that continued
      and prolonged use should be considered the main criterion for BZD addiction at
      this age, with or without increase in doses and failed attempt at cessation.
      Besides, the prescription of BZD increases after retirement and loneliness. 

PMID- 24026134
TI  - [An alternative word-list for the Free and cued selective reminding test (FCSRT):
      list presentation and reliability study].
AB  - The Free and cued selective reminding test (FCSRT) is one of the most effective
      neuropsychological test used to assess verbal memory in elderly people with
      memory problems. There are currently two lists of words: the initial French
      version (list A) and an alternative one (list B). However, diagnosing early
      Alzheimer's disease in memory clinics often requires more than two evaluations,
      particularly in patients with very mild cognitive symptoms and patients with
      young onset disease. Usually, memory tests can be affected by practice effect, so
      several expositions of the same list of words could limit its clinical utility.
      The aim of our study was to create and validate a second alternative version
      (list C). The study sample was composed of 222 healthy volunteers aged from 17 to
      84 years with a mean age of 44.6 years of whom 57% were females and 71% had a
      higher education. Within a two-month interval, each subject performed the test
      with one word-list and then the second one. The order of lists presentation was
      counterbalanced. Our findings indicate that the new alternative list (list C) is
      equivalent to the initial list of word (list A) for all the recall and
      recognition subscores, except the number of intrusive errors. This new list of
      words should be helpful to minimise potential practice effect and better assess
      memory decline in situations where the FCSRT has to be repeated across follow-up.

PMID- 24026135
TI  - [Effect of a non-pharmacological intervention, Voix d'Or((r)), on behavior
      disturbances in Alzheimer disease and associated disorders].
AB  - An innovative non-pharmacological intervention called Voix d'Or((r)) (Golden
      Voice) was proposed in the Cognitive behavioral unit (CBU) of the Memory center
      at the Hospices civils in Lyon. Voix d'Or((r)) offers eight sound activities
      disseminated via an audio device based on different approaches sociotherapeutic
      (music therapy, reminiscence, relaxation, reorientation in reality). The aim of
      this study was to test the effects of the Voix d'Or((r)) program on behavioral
      and psychological symptoms of dementia (BPSD) in patients with Alzheimer's
      disease hospitalized in the CBU. Twenty four patients with agitation and/or
      apathy and/or anxiety and/or depression were included. Patients were randomly
      selected in the intervention group exposed to Voix d'Or versus a control group
      exposed to usual occupational activities. Patients were assessed before (T0) and
      after (T1) the intervention period. Several variables were measured: frequency
      and severity of behavioral disorders, anxiety, depression, agitation and apathy.
      A significant improvement of anxiety level between T0 and T1was observed in the
      group with Voix d'Or((r)) compared to the control group. This study suggests that
      this non-pharmacological intervention may be beneficial on anxiety in patients
      with Alzheimer's disease. 

PMID- 24026136
TI  - Metallization of plasmid DNA for efficient gene delivery.
AB  - We report a facile one-pot synthesis of plasmid DNA-templated silver
      nanoparticles, which can be used as the platform for efficient gene delivery. 

PMID- 24026138
TI  - On the evaluation of vorticity using cardiovascular magnetic resonance velocity
      measurements.
AB  - Vorticity and vortical structures play a fundamental role affecting the
      evaluation of energetic aspects (mainly left ventricle work) of cardiovascular
      function. Vorticity can be derived from cardiovascular magnetic resonance (CMR)
      imaging velocity measurements. However, several numerical schemes can be used to
      evaluate the vorticity field. The main objective of this work is to assess
      different numerical schemes used to evaluate the vorticity field derived from CMR
      velocity measurements. We compared the vorticity field obtained using direct
      differentiation schemes (eight-point circulation and Chapra) and derivate
      differentiation schemes (Richardson 4* and compact Richardson 4*) from a
      theoretical velocity field and in vivo CMR velocity measurements. In all cases,
      the effect of artificial spatial resolution up-sampling and signal-to-noise ratio
      (SNR) on vorticity computation was evaluated. Theoretical and in vivo results
      showed that the eight-point circulation method underestimated vorticity. Up
      sampling evaluation showed that the artificial improvement of spatial resolution
      had no effect on mean absolute vorticity estimation but it affected SNR for all
      methods. The Richardson 4* method and its compact version were the most accurate
      and stable methods for vorticity magnitude evaluation. Vorticity field
      determination using the eight-point circulation method, the most common method
      used in CMR, has reduced accuracy compared to other vorticity schemes. Richardson
      4* and its compact version showed stable SNR using both theoretical and in vivo
      data. 

PMID- 24026139
TI  - Arsenic disulfide induces apoptosis of human diffuse large B cell lymphoma cells
      involving Bax cleavage.
AB  - The aim of the present study was to investigate the effect of arsenic disulfide
      (As2S2) on the proliferation and apoptosis of LY1 and LY8 human diffuse large B
      cell lymphoma (DLBCL) cells in an attempt to discover a more effective
      alternative therapy scheme. Human DLBCL cells LY1 and LY8 were treated with
      various concentrations of As2S2 for different time periods. Cell viability was
      detected by the CCK-8 assay; cell apoptosis was evaluated by flow cytometric
      analysis. The expression levels of Bax, Bcl-2 and caspase-3 were examined by
      quantitative PCR and western blotting. We found that the DLBCL cell viability was
      significantly decreased following treatment with As2S2 for 24, 48 and 72 h. Along
      with increasing As2S2 concentrations, the DLBCL cell viability was notably
      reduced when compared with the control group, and the results were statistically
      significant. Meanwhile, the apoptotic rates of DLBCL cells were significantly
      enhanced at 24, 48 and 72 h following treatment with increasing As2S2
      concentration, and the results were also statistically significant. The
      quantitative PCR results showed that at the mRNA level, the Bax/Bcl-2 expression
      ratio was increased and caspase-3 mRNA expression was upregulated in As2S2
      treated DLBCL cells. Western blot analysis revealed that at the protein level,
      As2S2 increased the Bax/Bcl-2 protein ratio in contrast to decreased pro-caspase
      3 expression in the DLBCL cells. Our findings also demonstrated that 21-kDa Bax
      was proteolytically cleaved into the 18-kDa Bax in the DLBCL cells exposed to
      As2S2 at a concentration of 10 uM. As2S2 inhibited proliferation and induced
      apoptosis of LY1 and LY8 cells in a concentration- and time-dependent manner. The
      effect was partly due to the induction of mitochondrial-dependent apoptosis
      involving Bax cleavage. 

PMID- 24026137
TI  - Norepinephrine and adenosine-5'-triphosphate synergize in inducing IL-6
      production by human dermal microvascular endothelial cells.
AB  - Endothelial cells (ECs) play important roles in cutaneous inflammation, in part,
      by release of inflammatory chemokines/cytokines. Because dermal blood vessels are
      innervated by sympathetic nerves, the sympathetic neurotransmitter norepinephrine
      (NE) and the co-transmitter adenosine-5'-triphosphate (ATP) may regulate
      expression of EC inflammatory factors. We focused on IL-6 regulation because it
      has many inflammatory and immune functions, including participation in Th17 cell
      differentiation. Strikingly, NE and ATP synergistically induced release of IL-6
      by a human dermal microvascular endothelial cell line (HMEC-1). Adrenergic
      antagonist and agonist studies indicated that the effect of NE on induced IL-6
      release is primarily mediated by beta2-adrenergic receptors (ARs). By real-time
      PCR IL-6 mRNA was also synergistically induced in HMEC-1 cells. This synergistic
      effect of NE and ATP was reproduced in primary human dermal endothelial cells
      (pHDMECs) and is also primarily mediated by beta2-ARs. Under conditions of
      stress, activation of the symphathetic nervous system may lead to release of ATP
      and NE by sympathetic nerves surrounding dermal blood vessels with induction of
      IL-6 production by ECs. IL-6 may then participate in immune and inflammatory
      processes including generation of Th17 cells. Production of IL-6 in this manner
      might explain stress-induced exacerbation of psoriasis, and perhaps, other skin
      disorders involving Th17-type immunity. 

PMID- 24026140
TI  - Clinical spectrum in CADASIL family with a new mutation.
AB  - BACKGROUND: Clinical presentation of CADASIL patients is variable due to the
      impact of other vascular risk factors and the type of a NOTCH3 mutation. This
      variability may impede the diagnosis of the disease. SUBJECTS AND METHODS: We
      report a comprehensive evaluation of several individuals in the CADASIL family
      whose member was identified to have the new mutation of NOTCH3 receptor on exon 6
      (p. G296C). We performed genetic testing, clinical and neuropsychological
      examination, cerebral MRI, Doppler sonography of cerebral arteries, fundoscopic
      examination and fluorescent angiography in six family members to determine the
      corresponding clinical spectrum associated with the new mutation. RESULTS AND
      CONCLUSION: The CADASIL mutation was detected in four individuals. Three of them
      were symptomatic, two having a history of stroke and one suffering from migraine.
      Although individuals had heterogeneous findings, the common feature included
      vascular changes that were present on cerebral and/or retinal arteries in all the
      mutation carriers even in one subject without clinical manifestation of the
      disease.

PMID- 24026141
TI  - Expression of miR-15a and miR-16-1 in patients with chronic lymphocytic leukemia.
AB  - INTRODUCTION: MicroRNAs (miRNAs) are small non-coding single-stranded RNA
      molecules that regulate gene expression at the post-transcriptional level. In the
      pathogenesis of chronic lymphocytic leukemia (CLL), miR-15a and miR-16-1 play an
      important role. These miRNAs are located on chromosome 13 in the 13q14.3 region,
      which is deleted in more than 55% of CLL patients. This aberration affects
      expression of miRNAs. OBJECTIVES: The study aimed at performing a molecular
      genetic analysis of miR-15a and miR-16-1 expression in a group of 39 patients
      diagnosed with CLL and determining the association between the expression of the
      two miRNAs and types of deletions in the 13q14 region. METHODS: We used
      fluorescence in situ hybridiziation (FISH) for determination of mono- or
      biallelic deletion 13q and quantitative polymerase chain reaction (Q-RT-PCR) to
      revealed expression miR-15a and miR-16-1 in 39 patients suffering from CLL.
      RESULTS: The analysis comprised 19 patients with monoallelic 13q14 deletion, 3
      patients with biallelic deletion, 9 patients with both monoallelic and biallelic
      deletions, and 8 patients without 13q14 deletion serving as controls. The results
      showed different levels of miRNA expression in individual patients. Significantly
      higher normalized levels of miR-15a expression were found in the control group
      and patients with monoallelic 13q14 expression compared with patients with
      biallelic deletion. There was a significantly decreased expression of both miRNAs
      in patients with biallelic deletion of the 13q14 region but only when deletions
      were present in 77% or more of cells, as detected by fluorescent in situ
      hybridization (FISH).

PMID- 24026142
TI  - Anti-hypertensive strategies in patients with MEtabolic parameters, DIabetes
      mellitus and/or NephropAthy (the M E D I N A study).
AB  - AIMS: The primary questions asked by the MEDINA (MEtabolic parameters, DIabetes
      mellitus and NephropAthy) study are: 1) Do angiotensin converting enzyme
      inhibitors (ACE-I) have any advantages over angiotensin receptor blockers (ARB)?
      2) Should the other drug for combination be a diuretic or a calcium-channel
      blocker (CCB)? 3) How are the risks reduced by the co administration of a statin?
      METHODS: A total of 439 hypertensive patients with metabolic syndrome and/or
      diabetes mellitus were randomized to 2 groups: group 1--ramipril (ACE-I) or
      perindopril and group 2--losartan (ARB). Hydrochlorothiazide (diuretic) or
      amlodipine (CCB) were added to both groups. As a third step, a statin was added.
      RESULTS: Blood pressure decreased 24.1/13.3 mmHg in the ACE inhibitor group and
      25.9/13.5 in the losartan group. The difference was insignificant. Adding either
      hydrochlorothiazide or amlodipin was equally effective. There were no significant
      differences on metabolic parameters in the trial arms. Cholesterol level
      decreased by 0.95 mmol/L in the ACE-I group and 1.02 mmol/L in the ARB group
      (ns). CONCLUSION: MEDINA has so far confirmed the equivalence of ACE-I and ARB in
      hypertension treatment. Adding either diuretic or CCB was equally effective. Our
      data support the current recommendations on adding a statin to reduce
      cardiovascular risk.

PMID- 24026143
TI  - Secondary hypertension and hirsutism as a clinical manifestation of tumor
      duplicity.
AB  - BACKGROUND: The differential diagnosis of the pathogenetic causes of hirsutism in
      combination with hypertension is a challenge for clinicians. METHODS AND RESULTS:
      This case report demonstrates a patient suffering from two hormonally active
      tumors - an adrenal adenoma with primary aldosteronism and a Leydig cell ovarian
      tumor with hyperandrogenism. The task of the authors was easier due to the
      perimenopausal age of the proband. Adrenal selective venous sampling was very
      helpful in the diagnosis of these active endocrine tumors. Both were resolved by
      a single laparoscopic surgery. CONCLUSION: The combination of the two described
      tumors is a unique clinical finding. The resolution using laparoscopy in a single
      procedure provided an elegant and efficient therapeutic approach.

PMID- 24026144
TI  - First experience with single incision laparoscopic surgery in Slovakia:
      concomitant cholecystectomy and splenectomy in an 11-year-old girl with
      hereditary spherocytosis.
AB  - AIMS: Hereditary spherocytosis is an autosomal dominant inheritance disorder of
      the red blood cell membrane characterized by the presence of spherical-shaped
      erythrocytes (spherocytes) in the peripheral blood. The main clinical features
      include haemolytic anemia, variable jaundice, splenomegaly and cholelithiasis
      caused by hyperbilirubinemia from erythrocyte hemolysis. Splenectomy does not
      solve the congenital genetic defect but it stops pathological hemolysis in the
      enlarged spleen. If gallstones are present, it is appropriate to perform
      cholecystectomy at the time of splenectomy, although the patient has symptoms of
      gall bladder disease. We present the case of single incision laparoscopic
      surgical (SILS) concomitant splenectomy and cholecystectomy performed with
      conventional laparoscopic instruments in an 11-year-old girl with the diagnosis
      of hereditary spherocytosis. METHODS: A 2-3 cm umbilical incision was used for
      the placement of two 5 mm trocars and one 10 mm flexible videoscope. Conventional
      laparoscopic dissector, grasper, Ligasure, Harmonic Ace and hemoclips were the
      main tools during surgical procedure. We prefer Single Incision Laparoscopic
      Surgery Foam Port (Covidien) as the single umbilical device for introduction into
      the abdominal cavity. First, we performed cholecystectomy, then the gallbladder
      was put aside over the liver and after that we peformed splenectomy. To remove
      the detached spleen and gallbladder, a nylon extraction bag is introduced through
      one of the port sites. The spleen is than morcellated in the bag with forceps and
      removed in fragments. After that we removed them and the umbilical fascial
      incision was closed. RESULT: Splenectomy is the only effective therapy for this
      disorder and often it is performed in combination with cholecystectomy.
      Conventional surgery requires a wide upper abdominal incision for correct
      exposure of the gallbladder and spleen. Our experience shows that SILS
      splenectomy and cholecystectomy is feasible even in young children and despite
      the small number of cases in the world, we consider the combined laparoscopic
      approach safe and effective for the treatment of hereditary spherocytosis.
      CONCLUSION: According to actually published guidelines, the laparoscopic approach
      to concomitant splenectomy and cholecystectomy is recommended, but it depends on
      the availability of appropriately trained surgeons and suitable equipment.

PMID- 24026145
TI  - Iterative reconstruction of pulmonary MDCT angiography: effects on image quality,
      effective dose and estimated organ dose to the breast.
AB  - AIMS: To compare the image characteristics, effective dose and estimated organ
      dose to the female breast in pulmonary MDCT angiography (MDCTA), reconstructed
      with either standard filtered back projection (FBP), or iterative reconstruction
      in image space (IRIS). METHODS: Pulmonary MDCTA performed in 116 females (age 18 
      77 years; body mass index 15 - 48) was reconstructed with FBP (n=52) or IRIS
      (n=64). Scans were acquired on a 128-row MDCT system using automatic tube current
      modulation, 100 kV tube voltage, and a quality reference mAs value of 120 (FBP)
      and 80 (IRIS). Dose was calculated from CT dose index (CTDIvol) and dose length
      product (DLP) values utilising ImPACT software. Image noise was measured within
      the pulmonary artery. Qualitative visual assessment of the scans was performed
      (1=negligible noise, 5=noise obscuring diagnostic information). RESULTS: The
      average CTDIvol yielded 4.33 mGy for FBP and 3.54 mGy for IRIS, respectively
      (18.2% decrease). The average effective scan dose was 2.73+/-0.57 mSv (FBP) and
      2.29+/-0.68 mSv (IRIS), respectively (16.1% decrease). The estimated average
      organ dose to the breast decreased from 5.1+/-1.1 mGy (FBP) to 4.2+/-1.2 mGy
      (IRIS, 17.6% decrease). No non-diagnostic scans (score 5) were encountered in
      either group. Significant improvement in image noise levels (P<0.01) and
      subjective image quality (P<0.02) were noted in IRIS group. CONCLUSION: Pulmonary
      MDCTA utilizing a 100 kV technique, automatic tube current modulation, and
      iterative image reconstruction offers robust results in routine conditions among
      an unselected female population, with breast doses being comparable to two-view
      digital mammography. Moreover, iterative reconstruction offers improvements in
      both image noise and visual perception of the scans, thus suggesting a potential
      for further dose reduction.

PMID- 24026147
TI  - Disc herniations in the national football league.
AB  - STUDY DESIGN: Retrospective analysis of a prospectively collected database.
      OBJECTIVE: To determine the overall incidence, location, and type of disc
      herniations in professional football players to target treatment issues and
      prevention. SUMMARY OF BACKGROUND DATA: Disc herniations represent a common and
      debilitating injury to the professional athlete. The NFL's (National Football
      League's) Sports Injury Monitoring System is a surveillance database created to
      monitor the league for all injuries, including injuries to the cervical,
      thoracic, and lumbar spine. METHODS: A retrospective analysis was performed on
      all disc herniations to the cervical, thoracic, and lumbar spine during a 12
      season period (2000-2012) using the NFL's surveillance database. The primary data
      points included the location of the injury, player position, activity at time of
      injury, and playing time lost due to injury. RESULTS: During the 12 seasons, 275
      disc herniations occurred in the spine. In regard to location, 76% occurred in
      the lumbar spine and most frequently affected the L5-S1 disc. The offensive
      linemen were most frequently injured. As expected, blocking was the activity that
      caused most injuries. Lumbar disc herniations rose in prevalence and had a mean
      loss of playing time of more than half the season (11 games). Thoracic disc
      herniations led to the largest mean number of days lost overall, whereas players
      with cervical disc herniations missed the most practices. CONCLUSION: Disc
      herniations represent a significant cause of morbidity in the NFL. Although much
      attention is placed on spinal cord injuries, preventive measures targeting the
      cervical, thoracic, and lumbar spine may help to reduce the overall incidence of
      these debilitating injuries.Level of Evidence: N/A.

PMID- 24026146
TI  - Intravitreal anti-VEGF therapy for choroidal neovascularisation secondary to
      pathological myopia: 4-year outcome.
AB  - OBJECTIVE: To report the visual outcome after 4-year follow-up in a series of
      highly myopic eyes with choroidal neovascularisation (CNV) treated with
      antivascular endothelial growth factor (anti-VEGF) drugs. METHODS: A
      retrospective, non-randomised, multicentre, consecutive, interventional case
      series study was performed. 92 highly myopic eyes with subfoveal CNV were treated
      with intravitreal injection (IVI) of anti-VEGF. The initial protocol (1 vs 3
      injections) was dictated by surgeons' preferences and followed by an as-needed
      monthly regime. Best-corrected visual acuity (BCVA) was evaluated at baseline and
      then monthly. The primary aim was to analyse BCVA changes. The effect of age,
      spherical equivalent (SE) and treating drug were evaluated as secondary
      objectives. RESULTS: The mean age of the patients was 57 years (SD 14, range 30
      93). The mean number of letters read was 46.1 (SD 16.8, range 5-70) at baseline,
      55.5 (SD 18.6, range 10-85) at 12 months, 50.1 (SD 20.1, range 5-82) at 24
      months, 54.2 (SD 21.9, range 2-85) at 36 months and 53.1 (SD 22.5, range 1-83) at
      48 months (p=0.000, initial vs 12, 24 and 36 months; p=0.01 initial vs 48 months;
      Student t test for paired data). The mean total number of IVI was 4.9 (SD 5.4,
      range 1-29). SE and treating drug had no influence on the final visual outcome
      and number of injections required. CONCLUSIONS: Intravitreal bevacizumab and
      ranibizumab are effective therapies and show similar clinical effects in highly
      myopic CNV. Visual acuity gain is maintained at 4-year follow-up.

PMID- 24026148
TI  - Cervical spondylotic myelopathy: methodological approaches to evaluate the
      literature and establish best evidence.
AB  - STUDY DESIGN: Review of methods. OBJECTIVE: To provide a detailed description of
      the methods undertaken in the articles in this focus issue pertaining to cervical
      spondylotic myelopathy (CSM) and ossification of the posterior longitudinal
      ligament (OPLL) and to describe the process used to develop summary statements
      and clinical recommendations regarding factors associated with the mechanisms,
      diagnosis, progression, and treatment of CSM and OPLL. SUMMARY OF BACKGROUND
      DATA: We present methods used in conducting the systematic, evidence-based
      reviews and development of expert panel summary statements and clinical
      recommendations of the mechanisms, diagnosis, progression, and treatment of CSM
      and OPLL. Our intent is that clinicians will combine the information from these
      systematic reviews, narrative reviews, and primary research studies with an
      understanding of their own capacities and experience to better manage patients
      with CSM or OPLL and consider future research for the diagnosis and treatment of
      these diseases. METHODS: For the systematic reviews, which make up the bulk of
      the studies in this focus issue, a systematic search and critical review of the
      English language literature was undertaken for articles published on the
      mechanisms, diagnosis, progression, and treatment of CSM and OPLL. Articles were
      screened for relevance using a priori criteria and relevant articles were
      critically reviewed. Whether an article was included for review depended on
      whether the study question was descriptive, one of therapy, or one of prognosis.
      The strength of evidence for the overall body of literature in each topic area
      was determined by 2 independent reviewers considering risk of bias, consistency,
      directness, and precision of results using a modification of the Grading of
      Recommendation Assessment, Development and Evaluation criteria. Disagreements
      were resolved by consensus. Findings from articles meeting inclusion criteria
      were summarized. From these summaries, summary statements or clinical
      recommendations were formulated among subject experts through a modified Delphi
      process using the Grading of Recommendation Assessment, Development and
      Evaluation approach. Methods for the 2 primary research studies and the narrative
      reviews are also reviewed. RESULTS: Because of the nature of questions that
      needed to be addressed, not all studies in this focus issue were amenable to
      systematic review. As a result, this focus issue consists of several different
      article types, including 1 research protocol, 2 primary research studies, 2
      narrative literature reviews, 7 systematic reviews, and 3 articles that combine a
      systematic review component with either a narrative section (n = 2) or a provider
      survey (n = 1). In general, the strength of evidence ratings ranged from
      insufficient to moderate. Summary statements or clinical recommendations were
      made according to available evidence and study type: 16 summary statements were
      made across 8 articles, and 17 clinical recommendations were made across 9
      articles. Three articles had both summary statements and clinical
      recommendations, 5 had summary statements only, 6 had clinical recommendations
      only, and 1 (the research protocol) was not amenable to either. CONCLUSION:
      Systematic reviews, narrative reviews, and primary research studies were
      undertaken to understand the mechanisms, diagnosis, progression, and treatment of
      CSM and OPLL and to provide summary statements and clinical recommendations. This
      article reports the methods used in the studies in this focus issue. SUMMARY
      STATEMENTS: The objectives of this focus issue were met using a variety of
      article and study designs, each of which has some unique methodological aspects
      associated with it. The reader should refer to the full article in this issue for
      additional details specific to that topic. The methods for systematic review
      follow accepted standards for rigor and, together with the application of Grading
      of Recommendation Assessment, Development and Evaluation, are intended to allow
      for transparency in the process for creating the clinical recommendation.

PMID- 24026149
TI  - Seat belt syndrome with cauda equina syndrome: two unique cases in the same motor
      vehicle accident.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe the surgical technique and
      outcome of 2 cases of lap-shoulder belt injury involving burst fracture at L5 and
      cauda equina syndrome (CES). SUMMARY OF BACKGROUND DATA: Lap-shoulder belts have
      largely replaced lap belts in the front seats of cars, and therefore the concept
      of seat belt injury needs re-evaluation. METHODS: Two adults, the driver and
      front seat passenger in the same car involved in a collision, sustained lap
      shoulder belt injury. One developed L5 Denis type A burst fracture and the other
      developed L5 Denis type B burst fracture. Both had CES. They were surgically
      managed by decompression of the spinal canal, which included removal of
      retropulsed fragments without impacting them. Both patients received short
      segment transpedicle screws and rod system instrumentation without the fractured
      vertebra being included. RESULTS: The percentage of preoperative degree of canal
      displacement of the retropulsed fragment was 60% in one patient and 55% in the
      other based on computed tomography. The mechanism of injury in both patients
      might be axial loading. After surgical intervention, the CES including lower leg
      weakness/numbness and bladder/bowel dysfunction clinically improved in both
      patients. CONCLUSION: Two adults in the same car involved in a collision were
      wearing lap-shoulder belts, and 1 had Denis type A burst fracture at L5 and the
      other had Denis type B burst fracture at L5. Both developed CES after the
      accident. Both patients had a good clinical outcome after surgical treatment.

PMID- 24026151
TI  - Effectiveness of acupuncture for nonspecific chronic low back pain: a systematic
      review and meta-analysis.
AB  - STUDY DESIGN: A systematic review and meta-analysis of randomized controlled
      trials (RCTs). OBJECTIVE: To evaluate the totality of evidence in relation to the
      effectiveness of acupuncture for nonspecific chronic low back pain (NSCLBP).
      SUMMARY OF BACKGROUND DATA: Acupuncture has become a popular alternative for
      treating clinical symptoms of NSCLBP. A number of RCTs have examined the
      effectiveness of acupuncture in the treatment of NSCLBP. METHODS: A systematic
      literature search was completed without date or language restrictions up to May
      2012. Studies included in the review were RCTs that examined all forms of
      acupuncture that adhered to the Traditional Acupuncture Theory for treating
      NSCLBP. Outcome measures included impairment, activity limitation, and
      participation restriction. The methodological quality of the studies was examined
      using the Cochrane risk of bias tool. RESULTS: Thirty-two studies were included
      in the systematic review, of which 25 studies presented relevant data for the
      meta-analysis. Acupuncture had a clinically meaningful reduction in levels of
      self-reported pain (mean difference =-16.76 [95% confidence interval, -33.33 to 
      0.19], P = 0.05, I = 90%) when compared with sham, and improved function
      (standard mean difference =-0.94 [95% confidence interval, -1.41 to -0.47], P <
      0.00, I = 78%) when compared with no treatment immediately postintervention.
      Levels of function also clinically improved when acupuncture in addition to usual
      care, or electroacupuncture was compared with usual care alone. When acupuncture
      was compared with medications (NSAIDs, muscle relaxants, and analgesics) and
      usual care, there were statistically significant differences between the control
      and the intervention groups but these differences were too small to be of any
      clinical significance. There was no evidence in support of acupuncture over
      transcutaneous electrical nerve stimulation. CONCLUSION: This systematic review
      demonstrates that acupuncture may have a favorable effect on self-reported pain
      and functional limitations on NSCLBP. However, the results should be interpreted
      in the context of the limitations identified, particularly in relation to the
      heterogeneity in the study characteristics and the low methodological quality in
      many of the included studies. LEVEL OF EVIDENCE: 1.

PMID- 24026150
TI  - Chondrocyte-specific inhibition of beta-catenin signaling leads to dysplasia of
      the caudal vertebrae in mice.
AB  - STUDY DESIGN: To inhibit beta-catenin specifically signaling in chondrocytes Col2
      ICAT transgenic mice were generated. Anomalies in caudal vertebrae were detected
      during embryonic and postnatal stages of Col2-ICAT transgenic mice. OBJECTIVE: To
      determine the role of canonical beta-catenin signaling in caudal vertebral
      development. SUMMARY OF BACKGROUND DATA: beta-catenin signaling plays a critical
      role in skeletal development. Col2-ICAT transgenic mice were generated to
      selectively block beta-catenin signaling by overexpression of the ICAT gene in
      chondrocytes. METHODS: Tails of E16.5 transgenic embryos and adult Col2-ICAT
      transgenic mice and their wild-type littermates were collected and analyzed.
      Skeletal preparation, 3-dimensional micro-computed tomographic and histological
      analyses were performed to evaluate changes in the structure of caudal vertebrae.
      Bromodeoxyuridine labeling was performed to evaluate changes in chondrocyte
      proliferation in caudal vertebrae. RESULTS: Skeletal preparation and 3
      dimensional micro-computed tomographic analyses revealed bone deformation and
      angulated deformities in tail tissue in Col2-ICAT transgenic mice. Histological
      studies revealed abnormal bone development and dysplastic caudal vertebrae in
      Col2-ICAT transgenic mice. Inhibition of beta-catenin signaling in cartilage
      resulted in vertebral dysplasia leading to aberrant resegmenting process. Thus, 2
      poorly developed sclerotomes failed to fuse to form a complete vertebrae. BrdU
      labeling revealed a decreased chondrocyte proliferation in both cartilageous
      templates of transgenic embryos and the growth plate of adult Col2-ICAT
      transgenic mice. CONCLUSION: Wnt/beta-catenin signaling plays an important role
      in vertebral development. Inhibition of beta-catenin signaling in chondrocytes
      results in caudal vertebra deformity in mice, which may occur as early as in the
      stage of sclerotome formation. LEVEL OF EVIDENCE: N/A.

PMID- 24026153
TI  - Changes in pressure pain threshold in patients with chronic nonspecific low back
      pain.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: The purpose of this study is to
      compare pressure pain threshold (PPT) values between patients with chronic
      nonspecific low back pain (CLBP) and healthy individuals and correlate PPT values
      of the structures investigated with demographic and clinical data from patients
      with CLBP. SUMMARY OF BACKGROUND DATA: Chronic pain may decrease pain tolerance
      of almost the entire spinal cord segment; however, previous studies on PPT in
      patients with low back pain have limited their focus to evaluating only patient
      complaints. METHODS: Forty subjects participated in the study: 20 with a clinical
      diagnosis of CLBP and 20 healthy individuals. Outcome measures were PPT values of
      myotomes, sclerotomes, and dermatomes corresponding to segments L1 to S3;
      demographic, clinic, and social data; visual analogue scale, and Roland and
      Morris Questionnaire. RESULTS: Most analyzed structures had lower PPT values in
      patients with CLBP than in healthy individuals on both sides (bilaterally). PPT
      correlated positively with height and pain duration (P < 0.05) and negatively
      with body mass index in the suprainterspinous ligament between L2 and L3 and
      dermatomes L5 to S2 (P < 0.05). CONCLUSION: Our results showed that individuals
      with CLBP have lower PPT values than healthy individuals in almost all assessed
      structures. We propose a simple approach that can differentiate patients with
      CLBP whose hyperalgesia in the painful area may be the result of several
      mechanisms that should be further investigated, such as sensitization of the
      central nervous system. LEVEL OF EVIDENCE: N/A.

PMID- 24026154
TI  - Which instruments can detect submaximal physical and functional capacity in
      patients with chronic nonspecific back pain? A systematic review.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To evaluate the validity of
      instruments that claim to detect submaximal capacity when maximal capacity is
      requested in patients with chronic nonspecific musculoskeletal pain. SUMMARY OF
      BACKGROUND DATA: Several instruments have been developed to measure capacity in
      patients with chronic pain. The detection of submaximal capacity can have major
      implications for patients. The validity of these instruments has never been
      systematically reviewed. METHODS: A systematic literature search was performed
      including the following databases: Web of Knowledge (including PubMed and
      Cinahl), Scopus, and Cochrane. Two reviewers independently selected the articles
      based on the title and abstract according to the study selection criteria.
      Studies were included when they contained original data and when they objectified
      submaximal physical or functional capacity when maximal physical or functional
      capacity was requested. Two authors independently extracted data and rated the
      quality of the articles. The included studies were scored according to the
      subscales "Criterion Validity" and "Hypothesis Testing" of the COSMIN checklist.
      A Best Evidence Synthesis was performed. RESULTS: Seven studies were included, 5
      of which used a reference standard for submaximal capacity. Three studies were of
      good methodological quality and validly detected submaximal capacity with
      specificity rates between 75% and 100%. CONCLUSION: There is strong evidence that
      submaximal capacity can be detected in patients with chronic low back pain with a
      lumbar motion monitor or visual observations accompanying a functional capacity
      evaluation lifting test.

PMID- 24026155
TI  - Does bone cement in percutaneous vertebroplasty act as a stress riser?
AB  - STUDY DESIGN: An in vitro cadaveric study. OBJECTIVE: To determine whether
      percutaneous vertebroplasty (PVP) with a clinically relevant amount of bone
      cement is capable of causing stress peaks in adjacent-level vertebrae. SUMMARY OF
      BACKGROUND DATA: It is often suggested that PVP of a primary spinal fracture
      causes stress peaks in adjacent vertebrae, thereby leading to additional
      fractures. The in vitro studies that demonstrated this relationship, however, use
      bigger volumes of bone cement used clinically. METHODS: Ten fresh-frozen
      vertebrae were loaded until failure, while registering force and displacement as
      well as the pressure under the lower endplate. After failure, the vertebrae were
      augmented with clinically relevant amounts of bone cement and then again loaded
      until failure. The force, displacement, and pressure under the lower endplate
      were again registered. RESULTS: Stress peaks were not related to the location of
      the injected bone cement. Both failure load and stiffness were significantly
      lower after augmentation. CONCLUSION: On the basis of our findings, we conclude
      that vertebral augmentation with clinically relevant amounts of bone cement does
      not lead to stress peaks under the endplate. It is therefore unlikely that PVP,
      in itself, causes detrimental stresses in the adjacent vertebrae, leading to new
      vertebral fractures. LEVEL OF EVIDENCE: N/A.

PMID- 24026156
TI  - Cervical microendoscopic discectomy and fusion: does it affect the postoperative
      course and the complication rate? A blinded randomized controlled trial.
AB  - STUDY DESIGN: A blinded randomized controlled trial. OBJECTIVE: The purpose of
      this study was to evaluate the cervical microendoscopic discectomy and fusion.
      SUMMARY OF BACKGROUND DATA: Minimally invasive treatment of spinal disorders
      allows surgeons to have direct access to the pathology with a reduced surgical
      morbidity, which is reflected over the improved postoperative course. Minimally
      invasive techniques for cervical discectomy including the posterior
      microendoscopic discectomy and the percutaneous endoscopic discectomy have a high
      success rate but are limited by the narrow range of indications. Lately,
      preliminary reports about cervical microendoscopic discectomy and fusion (CMEDF)
      showed high success rates without restrictions in the indications. METHODS:
      Seventy consecutive patients were randomly assigned in 2 equal groups, the first
      operated by the "gold standard" anterior cervical discectomy and fusion and the
      second by CMEDF. Blinding included the patient-until dressing removal, the
      evaluating physician, and the radiologist throughout the entire study. The mean
      follow-up period was 28 months and outcome has been assessed using the Japanese
      Orthopaedic Association score, Odom criteria and the visual analogue scale. In
      addition, the operative time, complication rate, hospitalization, and the
      postoperative analgesic doses were recorded. RESULTS: The functional outcome of
      the CMEDF at the final follow-up was 91% good to excellent. Results in the open
      group were very similar. Meanwhile, CMEDF demonstrated improved cosmesis, reduced
      laryngopharyngeal complication rate, postoperative analgesics, and hospital stay.
      CONCLUSION: The results of the CMEDF are very promising. However, a much larger
      patient series from multicenter studies is still required for drawing up a final
      conclusion. LEVEL OF EVIDENCE: 1.

PMID- 24026157
TI  - Interspinous distraction in lumbar spinal stenosis: a neurophysiological
      perspective.
AB  - STUDY DESIGN: Prospective neurophysiological study. OBJECTIVE: To identify and
      quantify the neurophysiological effects of interspinous distraction during spine
      surgery for lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA:
      Interspinous devices have been introduced as an alternative treatment of LSS in
      selected patients aiming at obtaining indirect decompression. Nevertheless, there
      is no data on the immediate neurophysiological effect of distraction. METHODS:
      Thirty patients with LSS undergoing decompression (14 at single level, 16 at
      multiple levels) were enrolled, resulting in a total of 48 levels to be analyzed.
      Before decompression, calibrated incremental distraction simulating interspinous
      device implantation of 8, 10, 12, 14, and 16 mm was performed. Intraoperative
      motor evoked potentials were acquired before any distraction, during distraction
      at each incremental value and after bilateral decompression. We evaluated
      relative changes of motor evoked potentials normalized to hand muscles and
      related them to the number of affected levels, LSS radiological severity based on
      the A to D grading, lordosis, and disc height. RESULTS: For single-level disease,
      8-mm distraction and open decompression yielded similar improvement in motor
      evoked potentials not only in levels with morphological grades A or B, but also
      in levels with morphological grades C or D (i.e., severe or extreme stenosis) (P
      = 0.32). In contrast, distraction superior to 8 mm was less effective (P <=
      0.05). In multiple-level stenosis, decompression was significantly more effective
      than any degree of distraction (P < 0.001). No correlation of those results to
      disc height or lordosis was observed. Using chi trend test to analyze the effect
      of distraction, a linear trend favoring moderate over severe stenotic morphology
      was observed (P = 0.0349). CONCLUSION: Interspinous distraction of 8 mm is
      sufficient to replicate electrophysiological improvements obtained during full
      decompression even in severe single-level stenosis but not in multilevel disease.
      Interspinous distraction has therefore an immediately measurable
      neurophysiological effect. LEVEL OF EVIDENCE: 4.

PMID- 24026158
TI  - Complications of spinal fusion with utilization of bone morphogenetic protein: a
      systematic review of the literature.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: A systematic review was performed to
      identify the types of complications and complication rates associated with the
      use of bone morphogenetic protein (BMP) in both anterior and posterior cervical
      and lumbar spine surgery. SUMMARY OF BACKGROUND DATA: There has been an increase
      in BMP use in various clinical situations typically in an "off-label" fashion.
      Associated with its use, however, have been reports of various complications.
      METHODS: A MEDLINE search was conducted. All articles involving complications
      after spine surgery in patients receiving BMP were included. Articles were
      excluded on the basis of the following criteria: Non-English manuscripts and
      nonhuman subjects. A total of 29 articles met the inclusion and exclusion
      criteria and were used in the analysis. For each complication identified, the
      incidence was calculated by pooling the subjects from the studies that reported
      the complication. chi tests were used to compare the incidence rates between
      those that had received BMP and the control groups. RESULTS: Of the 29 articles
      included, 7 reported complication rates in anterior cervical fusions, 3 in
      posterior cervical fusions, 4 in anterior lumbar interbody fusions (ALIF), 9 in
      posterior/transforaminal lumbar interbody fusions (PLIF/TLIF), and 6 in
      posterolateral lumbar fusions. Individual complication rates when BMP was used
      was in the range from 0.66% to 20.1% in anterior cervical fusions, 3.5% to 14.6%
      in posterior cervical fusions, 2.0% to 7.3% in ALIFs, 1.5% to 21.8% in
      PLIF/TLIFs, and 1.4% to 8.2% in posterolateral lumbar fusions. Pseudarthrosis
      rates were statistically significantly lower with the utilization of BMP in all
      procedures except for PLIF/TLIFs, which only approached significance (P = 0.07).
      The only individual complication that was statistically significantly greater
      with BMP utilization was retrograde ejaculation in ALIFs (7.3 vs. 2.3%; P =
      0.03). The rate of dysphagia/swelling in anterior cervical fusions was greater
      with BMP (20.1 vs. 15.6%), however this only approached statistical significance
      (P = 0.07). CONCLUSION: The body of literature reports complication rates with
      BMP ranging from 0.66% to 21.8%. However, the only statistically significant
      adverse complication rate was retrograde ejaculation in the ALIF population
      (7.3%). Despite the increased awareness of complications associated with BMP,
      complication rates remain spine site specific and low. Thorough patient education
      should be done with the physician to make an informative use regarding BMP
      utilization in spinal surgery. LEVEL OF EVIDENCE: 3.

PMID- 24026159
TI  - Short-term usual chiropractic care for spinal pain: a randomized controlled
      trial.
AB  - STUDY DESIGN: Parallel-group randomized controlled trial. OBJECTIVE: Establish
      the short-term effectiveness of chiropractic therapy for spinal pain compared
      with a sham intervention and explore the predictors of chiropractic treatment
      satisfaction. SUMMARY OF BACKGROUND DATA: Chiropractic treatment is widely used
      for spinal pain. However, a lack of sound evidence precludes conclusions about
      the effectiveness of chiropractic for spinal pain. METHODS: Participants were
      adults experiencing spinal pain, randomized to receive 2 treatments of
      chiropractic or sham therapy. Participants and outcome assessors were blinded to
      group allocation. Primary outcomes at 2 weeks were pain intensity (0-10 scale)
      and function (0-40 Functional Rating Index). Secondary outcomes were global
      change, minimum acceptable outcome, and treatment satisfaction. Treatment effects
      were estimated with linear mixed models for the primary outcomes. We used
      logistic regression to identify differences in the secondary outcomes and explore
      for predictors of treatment satisfaction. RESULTS: One hundred eighty three
      participants (chiropractic, n = 92; sham, n = 91) were recruited and included in
      the analyses. Participants receiving chiropractic therapy reported greater
      improvements in pain (mean difference, 95% confidence interval [CI] = 0.5 [0.1
      0.9]), physical function (mean difference [95% CI] = 2.1 [0.3-4.0]), and were
      more likely to experience global improvement (48% vs. 24%, P = 0.01) and
      treatment satisfaction (78% vs. 56%, P < 0.01). There was no between-group
      difference in achieving a minimally acceptable outcome (34% sham vs. 29%
      chiropractic, P = 0.42). Awareness of treatment assignment and achieving
      minimally important improvement in pain intensity were associated with
      chiropractic treatment satisfaction. CONCLUSION: Short-term chiropractic
      treatment was superior to sham; however, treatment effects were not clinically
      important. Awareness of treatment assignment and clinically important reductions
      in pain were associated with chiropractic treatment satisfaction. LEVEL OF
      EVIDENCE: 2.

PMID- 24026163
TI  - What do we know about unassisted smoking cessation in Australia? A systematic
      review, 2005-2012.
AB  - CONTEXT: A significant proportion of smokers who quit do so on their own without
      formal help (ie, without professionally or pharmacologically mediated
      assistance), yet research into how smokers quit focuses primarily on assisted
      methods of cessation. OBJECTIVE: The aim of the present work was to
      systematically review recent smoking cessation research in Australia, a nation
      advanced in tobacco control, to determine what is known about smokers who quit
      unassisted in order to (1) inform a research agenda to develop greater
      understanding of the many smokers who quit unassisted and (2) elucidate possible
      lessons for policy and mass communication about cessation. METHODS: In January
      2013, four e-databases and the grey literature were searched for articles
      published between 2005 and 2012 on smoking cessation in Australia. Articles
      focusing solely on interventions designed to stimulate cessation were excluded,
      as were articles focusing solely on assisted cessation, leaving articles
      reporting on smokers who quit unassisted. Data from articles reporting on
      unassisted cessation were extracted and grouped into related categories. RESULTS:
      A total of 248 articles reported on smoking cessation, of which 63 focused solely
      on interventions designed to stimulate cessation, leaving 185 reporting on the
      method of cessation ('how' a smoker quits). Of these, 166 focused solely on
      assisted cessation, leaving 19 reporting, either directly or indirectly, on
      smokers who quit unassisted. Data from these studies indicated 54% to 69% of ex
      smokers quit unassisted and 41% to 58% of current smokers had attempted to quit
      unassisted. CONCLUSIONS: The majority of Australian smokers quit or attempt to
      quit unassisted, yet little research has been dedicated to understanding this
      process. Almost all research that reported unassisted cessation referenced it as
      a comparator to the focal point of assisted cessation. Public health may benefit
      from insights gained from greater research into the cessation method used by most
      smokers. Suggestions and a rationale for such research are provided.

PMID- 24026162
TI  - Design of the Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST).
AB  - STUDY DESIGN: Descriptive. OBJECTIVE: To describe the design and development of
      Bracing in Adolescent Idiopathic Scoliosis Trial (BrAIST). SUMMARY OF BACKGROUND
      DATA: Bracing has remained the standard of care for the nonoperative treatment of
      adolescent idiopathic scoliosis since the introduction of the Milwaukee brace in
      the late 1940s, but it has never been subjected to a rigorous evaluation of
      either its efficacy or its effectiveness. The BrAIST was designed to address the
      primary question: Do braces (specifically a thoracolumbosacral orthosis) lower
      the risk of curve progression to a surgical threshold (>=50 degrees ) in patients
      with adolescent idiopathic scoliosis relative to watchful waiting alone? METHODS:
      The authors describe the rationale for BrAIST, including the limitations of the
      current literature evaluating bracing for adolescent idiopathic scoliosis.
      Second, the authors describe the preliminary work, including the preparation of
      the National Institutes of Health clinical trials planning grant. Finally, the
      authors describe the trial design in detail. RESULTS: BrAIST was conducted in 25
      sites in North America. Subjects were treated either with a thoracolumbosacral
      orthosis or watchful waiting and followed every 6 months until they reached
      skeletal maturity or the surgical threshold of 50 degrees  Cobb angle.
      CONCLUSION: Clinical decision making will be improved by translation of the
      BrAIST results into evidence-based prognosis and estimates of how the prognosis,
      specifically the risk of progressing to surgery, may be altered by the use of
      bracing. LEVEL OF EVIDENCE: N/A.

PMID- 24026164
TI  - Age-related decline of myelin proteins is highly correlated with activation of
      astrocytes and microglia in the rat CNS.
AB  - It has been shown that aging can greatly influence the integrity and
      ultrastructure of white matter and the myelin sheath; however, studies regarding
      the effects of aging on the expression of myelin proteins are still limited. In
      the present study, immunohistochemical mapping was used to investigate the
      overall expression of myelin basic protein (Mbp) and myelin oligodendrocyte
      glycoprotein (Mog) in the central nervous system (CNS) of rats in postnatal
      months 2, 5, 18 and 26. Astrocyte and microglia activation was also detected by
      glial fibrillary acidic protein (GFAP) or ionized calcium-binding adaptor
      molecule 1 (Iba1) staining and western blotting. A significant decline of Mbp and
      Mog was identified as a universal alteration in the CNS of aged rats. Aging also
      induced significant astrocyte and microglial activation. Correlation analysis
      indicated a negative correlation between the reduction of age-related myelin
      proteins and glial activation in aging. This correlation of myelin breakdown and
      glial activation in aging may reveal new evidence in connecting the inflammation
      and myelin breakdown mechanism of age-related neurodegenerative diseases. 

PMID- 24026165
TI  - An entanglement-enhanced microscope.
AB  - Among the applications of optical phase measurement, the differential
      interference contrast microscope is widely used for the evaluation of opaque
      materials or biological tissues. However, the signal-to-noise ratio for a given
      light intensity is limited by the standard quantum limit, which is critical for
      measurements where the probe light intensity is limited to avoid damaging the
      sample. The standard quantum limit can only be beaten by using N quantum
      correlated particles, with an improvement factor of ?N. Here we report the
      demonstration of an entanglement-enhanced microscope, which is a confocal-type
      differential interference contrast microscope where an entangled photon pair
      (N=2) source is used for illumination. An image of a Q shape carved in relief on
      the glass surface is obtained with better visibility than with a classical light
      source. The signal-to-noise ratio is 1.35+/-0.12 times better than that limited
      by the standard quantum limit. 

PMID- 24026166
TI  - Redesigning a joint replacement program using Lean Six Sigma in a Veterans
      Affairs hospital.
AB  - IMPORTANCE: In April 2009, an analysis of joint replacement surgical procedures
      at the Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis,
      Indiana, revealed that total hip and knee replacements incurred $1.4 million in
      non-Veterans Affairs (VA) care costs with an average length of stay of 6.1 days
      during fiscal year 2008. The Joint Replacement Program system redesign project
      was initiated following the Vision-Analysis-Team-Aim-Map-Measure-Change-Sustain
      (VA-TAMMCS) model to increase efficiency, decrease length of stay, and reduce non
      VA care costs. OBJECTIVE: To determine the effectiveness of Lean Six Sigma
      process improvement methods applied in a VA hospital. DESIGN, SETTING, AND
      PARTICIPANTS: Perioperative processes for patients undergoing total joint
      replacement were redesigned following the VA-TAMMCS model--the VA's official,
      branded method of Lean Six Sigma process improvement. A multidisciplinary team
      including the orthopedic surgeons, frontline staff, and executive management
      identified waste in the current processes and initiated changes to reduce waste
      and increase efficiency. Data collection included a 1-year baseline period and a
      20-month sustainment period. MAIN OUTCOMES AND MEASURES: The primary endpoint was
      length of stay; a secondary analysis considered non-VA care cost reductions.
      RESULTS: Length of stay decreased 36% overall, decreasing from 5.3 days during
      the preproject period to 3.4 days during the 20-month sustainment period (P <
      .001). Non-VA care was completely eliminated for patients undergoing total hip
      and knee replacement at the Richard L. Roudebush Veterans Affairs Medical Center,
      producing an estimated return on investment of $1 million annually when compared
      with baseline cost and volumes. In addition, the volume of total joint
      replacements at this center increased during the data collection period.
      CONCLUSIONS AND RELEVANCE: The success of the Joint Replacement Program
      demonstrates that VA-TAMMCS is an effective tool for Lean and Six Sigma process
      improvement initiatives in a surgical practice, producing a 36% sustained
      reduction in length of stay and completely eliminating non-VA care for total hip
      and knee replacements while increasing total joint replacement volume at this
      medical center.

PMID- 24026168
TI  - Sagittal spinopelvic alignment in adolescent thoracic scoliosis secondary to
      Chiari I malformation: a comparison between the left and the right curves.
AB  - PURPOSE: To investigate whether the sagittal morphology differs between the left
      and right thoracic curves in patients with Chiari malformation-associated
      scoliosis (CMS). METHODS: Thirty-four patients with a left thoracic curve
      constituted the CM-L group, whereas 44 patients with a right thoracic curve were
      assigned into the CM-R group. Another cohort of 90 age- and gender-matched
      asymptomatic adolescents was enrolled to serve as the control group. Seven
      sagittal parameters were evaluated on standing lateral radiographs, including
      thoracic kyphosis (TK), lumbar lordosis (LL), thoracolumbar junctional kyphosis
      (TJK), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT) and
      sacral slope (SS). RESULTS: Compared to the normal controls, the TK, LL and SS
      were significantly greater in the CM-L group, along with a significantly
      decreased PT. Similar changes in SS and PT were also demonstrated in the CM-R
      group, while the TK and LL were found to be relatively normal compared with the
      control group. Concerning CMS patients with different curve directions,
      significantly increased TK and LL were observed in the CM-L group, whereas all
      three pelvic parameters were similar for the two groups. In addition, no
      significant differences were noted between the three groups in PI, TJK or SVA.
      Moreover, the LL was strongly related to the TK and SS in all three groups, but
      to the PI only in the control and CM-R groups. A significant correlation was also
      noted between TK and SS in the CM-L group. CONCLUSIONS: Significant differences
      in sagittal profiles indeed exist between CMS patients and healthy adolescents,
      as well as between CMS patients with different curve directions. In CMI patients
      with a left thoracic curve, compensatory alterations appear to occur in LL in
      response to the increased TK to maintain a balanced posture.

PMID- 24026169
TI  - Answer to the Letter to the Editor of K. Shubhakaran et al. entitled "Backache
      and infection" concerning "Antibiotic treatment in patients with chronic low back
      pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized
      controlled trial of efficacy" by Albert H.B. et al., Eur Spine J (2013) 22:697
      707.

PMID- 24026170
TI  - Answer to the Letter to the Editor of Zafar Ahmad et al. concerning "Antibiotic
      treatment in patients with chronic low back pain and vertebral bone edema (Modic
      type 1 changes): a double-blind randomized controlled trial of efficacy" by
      Albert HB et al., Eur Spine J (2013) 22:697-707.

PMID- 24026171
TI  - Quantification of cerebral hemodynamics.

PMID- 24026172
TI  - High-resolution mapping of zym, a recessive gene for Zucchini yellow mosaic virus
      resistance in cucumber.
AB  - KEY MESSAGE: Using a high-resolution mapping approach, we identified a candidate
      gene for ZYMV resistance in cucumber. Our findings should assist the development
      of high-versatility molecular markers for MAS for ZYMV resistance. Zucchini
      yellow mosaic virus (ZYMV) causes significant disease, which leads to fruit yield
      loss in cucurbit crops. Since ZYMV resistance is often inherited recessively in
      cucumber, marker-assisted selection (MAS) is a useful tool for the development of
      resistant cucumber cultivars. Using 128 families of an F2:3 population derived
      from a cross between susceptible 'CS-PMR1' and resistant 'A192-18' cucumber
      inbred lines, we confirmed that ZYMV resistance is conferred by a single
      recessive locus: zym (A192-18) . We constructed a cucumber genetic linkage map
      that included 125 simple sequence repeat (SSR) markers segregating into 7 linkage
      groups (chromosomes). The zym (A192-18) locus was mapped to chromosome 6, at
      genetic distances of 0.9 and 1.3 cM from two closely linked SSR markers. For high
      resolution genetic mapping, we identified new molecular markers cosegregating
      with the zym (A192-18) locus; using cucumber genomic and molecular marker
      resources and screening an F2 population of 2,429 plants, we narrowed down the
      zym (A192-18) locus to a <50-kb genomic region flanked by two SSR markers, which
      included six candidate genes. Sequence analysis of the candidate genes' coding
      regions revealed that the vacuolar protein sorting-associated protein 4-like
      (VPS4-like) gene had two SNPs between the parental lines. Based on SNPs of the
      VPS-4-like gene, we developed zym (A192-18) -linked DNA markers and found that
      genotypes associated with these markers were correlated with the ZYMV resistance
      phenotype in 48 cucumber inbred lines. According to our data, the gene encoding
      VPS4-like protein is a candidate for the zym (A192-18) locus. These results may
      be valuable for MAS for ZYMV resistance in cucumber.

PMID- 24026173
TI  - Evidence of diagnostic enhancement pattern in hepatocellular carcinoma nodules
      <=2 cm according to the AASLD/EASL revised criteria.
AB  - PURPOSE: To define the percentage of small (<=2 cm) hepatocellular carcinoma
      (HCC) nodules showing the diagnostic enhancement pattern at CEUS, computed
      tomography (CT), and gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic
      resonance (MR) imaging. METHODS: 42 cirrhotic patients (26 male, 16 female; 67 +/
      12 years) with 46 biopsy-proven HCCs <=2 cm were included. Each HCC was scanned
      by CEUS, contrast-enhanced CT, and Gd-BOPTA-enhanced MR imaging. Nodule
      enhancement was evaluated by two readers. Independent analysis was followed by
      consensual analysis and the proportion of HCCs with the diagnostic enhancement
      pattern (nodule hyperenhancing on hepatic arterial phase and hypoenhancing on
      portal venous-late phase) on CEUS, CT, and MR imaging was compared by chi-square
      test. RESULTS: Very good inter-reader agreement was observed on hepatic arterial
      phase and portal venous-late phase: CEUS, k = 0.89 and 0.85; CT, k = 0.91 and
      0.88; MR imaging, k = 0.96 and 0.94. CEUS and CT did not differ in the percentage
      of HCC nodules with a diagnostic enhancement pattern (18/46 and 16/46; P = 0.66),
      while MR imaging revealed the diagnostic pattern in higher percentage of nodules
      (29/46; P = 0.012) in comparison to CEUS and CT. CONCLUSIONS: CEUS and contrast
      enhanced CT did not differ in the percentage of small HCC nodules with diagnostic
      enhancement pattern, while Gd-BOPTA-enhanced MR imaging revealed the diagnostic
      pattern in a higher nodule number in comparison to CEUS and CT.

PMID- 24026174
TI  - CT angiography in the abdomen: a pictorial review and update.
AB  - The development of multidetector CT technology and helical scanning techniques
      has revolutionized the use of CT for primary diagnostic evaluation of the
      abdominal vasculature, particularly the arterial system. CT angiography has
      numerous benefits relative to conventional catheter angiography, and has largely
      replaced catheter-based techniques in many clinical algorithms. This pictorial
      review and update will cover important technical principles related to modern CT
      angiography (including contrast delivery and dose considerations), discuss
      relevant anatomy and variants, and illustrate numerous arterial conditions
      related to the abdominal aorta and branch vessels. 

PMID- 24026175
TI  - Pluronic polymer capped biocompatible mesoporous silica nanocarriers.
AB  - A facile self-assembly method is described to prepare PEGylated silica
      nanocarriers using hydrophobic mesoporous silica nanoparticles and a pluronic
      F127 polymer. Pluronic capped nanocarriers revealed excellent dispersibility in
      biological media with cyto- and blood compatibilities. 

PMID- 24026176
TI  - YY1 binds to alpha-synuclein 3'-flanking region SNP and stimulates antisense
      noncoding RNA expression.
AB  - alpha-synuclein (SNCA) is an established susceptibility gene for Parkinson's
      disease (PD), one of the most common human neurodegenerative disorders. Increased
      SNCA is considered to lead to PD and dementia with Lewy bodies. Four single
      nucleotide polymorphisms (SNPs) in SNCA 3' region were prominently associated
      with PD among different ethnic groups. To examine how these SNPs influence
      disease susceptibility, we analyzed their potential effects on SNCA gene
      expression. We found that rs356219 showed allele-specific features. Gel shift
      assay using nuclear extracts from SH-SY5Y cells showed binding of one or more
      proteins to the protective allele, rs356219-A. We purified the rs356219-A-protein
      complex with DNA affinity beads and identified a bound protein using mass
      spectrometry. This protein, YY1 (Yin Yang 1), is an ubiquitous transcription
      factor with multiple functions. We next investigated SNCA expression change in SH
      SY5Y cells by YY1 transfection. We also analyzed the expression of antisense
      noncoding RNA (ncRNA) RP11-115D19.1 in SNCA 3'-flanking region, because rs356219
      is located in intron of RP11-115D19.1. Little change was observed in SNCA
      expression levels; however, RP11-115D19.1 expression was prominently stimulated
      by YY1. In autopsied cortices, positive correlation was observed among RP11
      115D19.1, SNCA and YY1 expression levels, suggesting their functional
      interactions in vivo. Knockdown of RP11-115D19.1 increased SNCA expression
      significantly in SH-SY5Y cells, suggesting its repressive effect on SNCA
      expression. Our findings of the protective allele-specific YY1 and antisense
      ncRNA raised a novel possible mechanism to regulate SNCA expression. 

PMID- 24026177
TI  - Derived variants at six genes explain nearly half of size reduction in dog
      breeds.
AB  - Selective breeding of dogs by humans has generated extraordinary diversity in
      body size. A number of multibreed analyses have been undertaken to identify the
      genetic basis of this diversity. We analyzed four loci discovered in a previous
      genome-wide association study that used 60,968 SNPs to identify size-associated
      genomic intervals, which were too large to assign causative roles to genes.
      First, we performed fine-mapping to define critical intervals that included the
      candidate genes GHR, HMGA2, SMAD2, and STC2, identifying five highly associated
      markers at the four loci. We hypothesize that three of the variants are likely to
      be causative. We then genotyped each marker, together with previously reported
      size-associated variants in the IGF1 and IGF1R genes, on a panel of 500 domestic
      dogs from 93 breeds, and identified the ancestral allele by genotyping the same
      markers on 30 wild canids. We observed that the derived alleles at all markers
      correlated with reduced body size, and smaller dogs are more likely to carry
      derived alleles at multiple markers. However, breeds are not generally fixed at
      all markers; multiple combinations of genotypes are found within most breeds.
      Finally, we show that 46%-52.5% of the variance in body size of dog breeds can be
      explained by seven markers in proximity to exceptional candidate genes. Among
      breeds with standard weights <41 kg (90 lb), the genotypes accounted for 64.3% of
      variance in weight. This work advances our understanding of mammalian growth by
      describing genetic contributions to canine size determination in non-giant dog
      breeds. 

PMID- 24026179
TI  - Relationship duration moderates associations between attachment and relationship
      quality: meta-analytic support for the temporal adult romantic attachment model.
AB  - Although research has examined associations between attachment dimensions and
      relationship outcomes, theory has ignored how these associations change over time
      in adult romantic relationships. We proposed the Temporal Adult Romantic
      Attachment (TARA) model, which predicts that the negative associations between
      anxious and avoidant attachment on one hand and relationship satisfaction and
      commitment on the other will be more negative as relationship durations increase.
      Meta-analyses largely confirmed that negative associations between both insecure
      attachment dimensions and both relationship outcomes were more negative among
      longer relationship durations in cross-sectional samples. We also explored gender
      differences in these associations. The present review not only integrates the
      literature on adult attachment and romantic relationship satisfaction/commitment
      but also highlights the importance of relationship duration as a key moderator of
      the associations among these variables. We discuss the broad implications of
      these effects and our meta-analytic findings for the TARA model, attachment
      theory, and romantic relationships. 

PMID- 24026178
TI  - Analysis of variable retroduplications in human populations suggests coupling of
      retrotransposition to cell division.
AB  - In primates and other animals, reverse transcription of mRNA followed by genomic
      integration creates retroduplications. Expressed retroduplications are either
      "retrogenes" coding for functioning proteins, or expressed "processed
      pseudogenes," which can function as noncoding RNAs. To date, little is known
      about the variation in retroduplications in terms of their presence or absence
      across individuals in the human population. We have developed new methodologies
      that allow us to identify "novel" retroduplications (i.e., those not present in
      the reference genome), to find their insertion points, and to genotype them.
      Using these methods, we catalogued and analyzed 174 retroduplication variants in
      almost one thousand humans, which were sequenced as part of Phase 1 of The 1000
      Genomes Project Consortium. The accuracy of our data set was corroborated by (1)
      multiple lines of sequencing evidence for retroduplication (e.g., depth of
      coverage in exons vs. introns), (2) experimental validation, and (3) the fact
      that we can reconstruct a correct phylogenetic tree of human subpopulations based
      solely on retroduplications. We also show that parent genes of retroduplication
      variants tend to be expressed at the M-to-G1 transition in the cell cycle and
      that M-to-G1 expressed genes have more copies of fixed retroduplications than
      genes expressed at other times. These findings suggest that cell division is
      coupled to retrotransposition and, perhaps, is even a requirement for it. 

PMID- 24026180
TI  - Renal ammonium excretion after an acute acid load: blunted response in uric acid
      stone formers but not in patients with type 2 diabetes.
AB  - Idiopathic uric acid nephrolithiasis is characterized by elevated urinary net
      acid excretion and insufficient buffering by ammonium, resulting in excessively
      acidic urine and titration of the relatively soluble urate anion to insoluble
      uric acid. Patients with type 2 diabetes have similar changes in urinary pH, net
      acid excretion, and ammonium in 24-h urine collections at baseline, even after
      controlling for dietary factors, and are at increased risk for uric acid
      nephrolithiasis. However, not all patients with type 2 diabetes develop kidney
      stones, suggesting that uric acid stone formers may have additional urinary
      defects, perhaps not apparent at baseline. We performed a metabolic study of 14
      patients with idiopathic uric acid nephrolithiasis, 13 patients with type 2
      diabetes, and 8 healthy control subjects of similar body mass index. After
      equilibration on a fixed diet for 5 days, subjects were given a single oral acid
      load (50 meq ammonium chloride), and urine was collected hourly for 4 h. Uric
      acid stone formers had a lower ammonium excretory response to acute acid loading
      compared with diabetic and nondiabetic nonstone formers, suggesting that an
      ammonium excretory defect unique to uric acid stone formers was unmasked by the
      acid challenge. The Zucker diabetic fatty rat also did not show impaired urinary
      ammonium excretion in response to acute acid challenge. A blunted renal ammonium
      excretory response to dietary acid loads may contribute to the pathogenesis of
      idiopathic uric acid nephrolithiasis.

PMID- 24026181
TI  - Development of enzyme-linked immunosorbent assays for urinary thiazide-sensitive
      Na-Cl cotransporter measurement.
AB  - The Na-Cl cotransporter (NCC) in the distal convoluted tubules in kidney is known
      to be excreted in urine. However, its clinical significance has not been
      established because of the lack of quantitative data on urinary NCC. We developed
      highly sensitive enzyme-linked immunosorbent assays (ELISAs) for urinary total
      NCC (tNCC) and its active form, phosphorylated NCC (pNCC). We first measured the
      excretion of tNCC and pT55-NCC in urinary exosomes in pseudohypoaldosteronism
      type II (PHAII) patients since PHAII is caused by NCC activation. Highly
      increased excretion of tNCC and pNCC was observed in PHAII patients. In contrast,
      the levels of tNCC and pNCC in the urine of patients with Gitelman's syndrome
      were not detectable or very low, indicating that both assays could specifically
      detect the changes in urinary NCC excretion caused by the changes of NCC activity
      in the kidney. Then, to test whether these assays could be feasible for a more
      general patient population, we measured tNCC and pNCC in the urine of outpatients
      with different clinical backgrounds. Although urinary protein levels >30 mg/dl
      interfered with our ELISA, we could measure urinary pNCC in all patients without
      proteinuria. Thus we established highly sensitive and quantitative assays for
      urinary NCC, which could be valuable tools for estimating NCC activity in vivo.

PMID- 24026183
TI  - CD44v3-v10 reduces the profibrotic effects of TGF-beta1 and attenuates tubular
      injury in the early stage of chronic obstructive nephropathy.
AB  - CD44 family members are cell surface glycoproteins, which are expressed on
      tubular epithelial cells (TEC) solely upon kidney injury and are involved in
      renal fibrosis development. Renal interstitial fibrosis is the final
      manifestation of chronic kidney diseases and is regulated by a complex network of
      cytokines, including the profibrotic factor transforming growth factor-beta1 (TGF
      beta1) and the two antifibrotic cytokines bone morphogenic protein-7 (BMP-7) and
      hepatocyte growth factor (HGF). The present study investigates the potential role
      of CD44 standard (CD44s) and CD44v3-v10 (CD44v3) isoforms as modulators of the
      balance between TGF-beta1 and HGF/BMP-7. CD44s is the shortest and most common
      isoform. CD44v3-v10 (CD44v3) has heparan sulfate moieties, which enable the
      binding to HGF/BMP-7, and hence, might exert renoprotective effects. Using
      transgenic mice overexpressing either CD44s or CD44v3 specifically on proximal
      TEC, we found that in vitro the overexpression of CD44v3 on primary TEC renders
      cells less susceptible to TGF-beta1 profibrotic actions and more sensitive to BMP
      7 and HGF compared with TEC overexpressing CD44s. One day after unilateral
      ureteric obstruction, obstructed kidneys from CD44v3 transgenic mice showed less
      tubular damage and myofibroblasts accumulation, which was associated with
      decreased TGF-beta1 signaling and increased BMP-7 synthesis and signaling
      compared with kidneys from wild-type and CD44s transgenic mice. These data
      suggest that CD44v3 plays a renoprotective role in early stage of chronic
      obstructive nephropathy.

PMID- 24026182
TI  - Mineralocorticoid receptor antagonizes Dot1a-Af9 complex to increase alphaENaC
      transcription.
AB  - Aldosterone is a major regulator of Na(+) absorption and acts by activating the
      mineralocorticoid receptor (MR) to stimulate the epithelial Na(+) channel (ENaC).
      MR(-/-) mice exhibited pseudohypoaldosteronism type 1 (hyponatremia,
      hyperkalemia, salt wasting, and high levels of aldosterone) and died around
      postnatal day 10. However, if and how MR regulates ENaC transcription remain
      incompletely understood. Our earlier work demonstrated that aldosterone activates
      alphaENaC transcription by reducing expression of Dot1a and Af9 and by impairing
      Dot1a-Af9 interaction. Most recently, we reported identification of a major Af9
      binding site in the alphaENaC promoter and upregulation of alphaENaC mRNA
      expression in mouse kidneys lacking Dot1a. Despite these findings, the putative
      antagonism between the MR/aldosterone and Dot1a-Af9 complexes has never been
      addressed. The molecular defects leading to PHA-1 in MR(-/-) mice remain elusive.
      Here, we report that MR competes with Dot1a to bind Af9. MR/aldosterone and Dot1a
      Af9 complexes mutually counterbalance ENaC mRNA expression in inner medullary
      collecting duct 3 (IMCD3) cells. Real-time RT-quantitative PCR revealed that 5
      day-old MR(-/-) vs. MR(+/+) mice had significantly lower alphaENaC mRNA levels.
      This change was associated with an increased Af9 binding and H3 K79
      hypermethylation in the alphaENaC promoter. Therefore, this study identified MR
      as a novel binding partner and regulator of Af9 and a novel mechanism coupling MR
      mediated activation with relief of Dot1a-Af9-mediated repression via MR-Af9
      interaction. Impaired ENaC expression due to failure to inhibit Dot1a-Af9 may
      play an important role in the early stages of PHA-1 (before postnatal day 8) in
      MR(-/-) mice.

PMID- 24026185
TI  - Chronic eosinophilic pneumonia in a breast cancer patient post-radiation therapy:
      a case report.

PMID- 24026184
TI  - Long-term acute care patients weaning from prolonged mechanical ventilation
      maintain circadian rhythm.
AB  - BACKGROUND: Circadian rhythm regulates many physiologic and immunologic
      processes. Disruption of these processes has been demonstrated in acutely ill,
      mechanically ventilated patients in the ICU setting. Light has not been studied
      as an entraining stimulus in the chronically mechanically ventilated patient. The
      purpose of this study was to determine the association of naturally occurring
      ambient light levels in a long-term acute care (LTAC) hospital with circadian
      rhythm in patients recovering from critical illness and requiring prolonged
      mechanical ventilation (PMV). METHODS: We performed a prospective observational
      study of 15 adult patients who were recovering from critical illness and
      receiving PMV and who were admitted to the ventilator weaning unit at an LTAC
      hospital. Demographic data were obtained from chart review. Light stimuli in each
      patient room were assessed using a photometer device placed at eye level.
      Circadian rhythm was assessed by wrist actigraphy. Cumulative data were obtained
      from each device for a 48-h period, averaged into 4-h intervals, and analyzed.
      RESULTS: Patients receiving PMV were obese (mean body mass index of 32.7 +/- 10.3
      kg/m2) and predominantly female (73%) and had an average age of 63.1 +/- 14.3 y.
      Light exposure to this cohort maintained diurnal variation (P < .001) and was
      significantly different across time periods. Circadian rhythm, as represented by
      actigraphy, also maintained diurnal variation (P < .001) and was in phase with
      light. Linear regression of movement and time demonstrated a moderate
      relationship between light and actigraphy (R2 = 0.56). CONCLUSIONS: Despite
      requiring continued high-level care and a prolonged stay in a medical facility,
      patients recovering from critical illness and actively weaning from PMV maintain
      their circadian rhythm in phase with normal diurnal variations of light.

PMID- 24026186
TI  - Unilateral primary lung hypoplasia diagnosed in adulthood.
AB  - Unilateral primary pulmonary hypoplasia is rare in adulthood. It is usually
      present in the neonatal period or in early childhood, and is characterized by a
      decreased number of bronchial segments and decreased/absent alveolar air space.
      Most patients have recurrent episodes of wheezing or pneumonia and severe
      respiratory distress leading to chronic respiratory failure, whereas some
      patients may occasionally be asymptomatic. Herein, we present a case of left lung
      hypoplasia in an asymptomatic 28-year-old male, who was admitted to the hospital
      for further investigation of an abnormal result on a chest radiograph that was
      obtained as part of a health evaluation for military service. A thorough workup,
      including imaging modalities and bronchoscopy, disclosed a hypoplastic left lung,
      which had gone undiagnosed for 25 years. Embryological, clinical, and diagnostic
      aspects are briefly discussed. 

PMID- 24026187
TI  - The correlation between esophageal and abdominal pressures in mechanically
      ventilated patients undergoing laparoscopic surgery.
AB  - BACKGROUND: Intrathoracic pressure in patients undergoing laparoscopic surgery
      may be affected by intra-abdominal pressure during surgery. We investigated the
      relationship between intra-abdominal pressure (Pabd) and esophageal pressure
      (Pes) in mechanically ventilated patients undergoing laparoscopic surgery.
      METHODS: We prospectively studied 43 consenting patients over 18 y of age who
      were scheduled for elective laparoscopic surgery with plans for intra-operative
      intubation and paralysis. After establishing a good level of inter-observer
      agreement on Pes measurements, Pes was measured by one observer for each patient
      using an esophageal catheter. Pabd and Pes were recorded before and after
      abdominal insufflation. We used regression analysis to model the relationship
      between Pabd and Pes. RESULTS: Patients' ages varied from 22 to 78 y, with a mean
      of 53.2 +/- 14.6 y. Body mass index (BMI) varied from 13.7 to 60.5 kg/m2, with a
      mean of 33.7 +/- 10.5. PEEP was 5-7 cm H2O for 19 patients and 0 cm H2O for the
      remainder. Most patients underwent gastric bypass surgery (n = 11); others
      underwent hernia repair (n = 9), colon resection (n = 7), cholecystectomy (n =
      6), and various other surgeries (n = 10). Using univariate analyses, baseline
      Pabd was significantly correlated with baseline Pes (estimate of model
      coefficient [95% CI]: 0.79 [0.36-1.21], R2 = 0.24, P = .001), as was BMI (0.29
      [0.19-0.40], R(2) = 0.41, P < .001). However, a multivariable analysis showed no
      significant correlation with baseline Pabd (0.10 [-0.46 to 0.65], P = .73),
      whereas BMI remained highly significant (0.27 [0.11-00.43], P = .001) with R2 =
      0.40. Due to unexpected uniformity of abdominal inflation pressures (generally
      20.4 cm H2O) during surgery, data were not amenable to assessment of correlation
      between changes in abdominal and esophageal pressures after inflation.
      CONCLUSION: There was a limited correlation between baseline Pes and Pabd in
      patients undergoing elective laparoscopic surgery, suggesting a limited value of
      Pabd measurements in the management of mechanically ventilated patients.

PMID- 24026188
TI  - Neonatal and pediatric manual hyperinflation: influence of oxygen flow on
      ventilation parameters.
AB  - BACKGROUND: Although self-inflating bags are widely used for manual
      hyperinflation, they do not allow ventilation parameters, such as pressure or
      volume, to be set. We studied the ventilation performance of neonatal and
      pediatric self-inflating bags. METHODS: We asked 22 physiotherapists to manually
      hyperinflate 2 lung models (neonatal and pediatric), using self-inflating bags
      from 3 manufactures (Hudson, Laerdal, and JG Moriya), with flows of 0, 5, 10, and
      15 L/min. A pneumotachograph recorded tidal volume (V(T)), peak inspiratory
      pressure (PIP), peak inspiratory flow (PIF), peak expiratory flow (PEF), and
      inspiratory time. RESULTS: The V(T), PIP, and inspiratory time delivered by the
      Hudson, Laerdal, and JG Moriya bags, in both neonatal and pediatric self
      inflating bags, were significantly different (P < .001). The PEF and PIF
      delivered were different only when using the neonatal self-inflating bags (P <
      .001). The V(T), PIP, and PIF delivered with a flow of 0 L/min were lower than
      with 15 L/min (P < .05) with all the tested bags, in both the neonatal and
      pediatric sizes. CONCLUSIONS: The performance of the tested neonatal and
      pediatric bags varied by manufacturer and oxygen flow. There was an increase in
      VT, PIP, and PIF related to the increase of oxygen flow from 0 L/min to 15 L/min.
      The neonatal bags showed higher ventilation parameters variation than the
      pediatric bags.

PMID- 24026189
TI  - Adult diagnosis of Swyer-James-Macleod syndrome: retrospective analysis of four
      cases.
AB  - Swyer-James-Macleod syndrome (SJMS) is a rare constrictive bronchiolitis with air
      flow obstruction and a decreased number and diameter of ipsilateral peripheral
      pulmonary vessels. This syndrome is characterized by unilateral hyperlucency on
      chest radiography. Computed tomography provides useful additional information.
      The diagnosis is usually made in childhood but sometimes occurs in adulthood. The
      disease often presents with dyspnea, decreased exercise tolerance, cough,
      hemoptysis, and recurrent pulmonary infections. SJMS may be confused with asthma
      or pulmonary embolism due to similar symptoms and may result in inappropriate
      therapy. This case series examined the clinical and imaging spectrum of four
      patients who were diagnosed with SJMS in adulthood. 

PMID- 24026190
TI  - Pathological breathing patterns after pneumococcal rhombencephalitis.

PMID- 24026191
TI  - Pulmonary function of patients with chronic neck pain: a spirometry study.
AB  - BACKGROUND: Chronic neck pain is one of the most common musculoskeletal pain
      conditions experienced by many people during their lives. Although patients with
      neck pain are managed predominantly as musculoskeletal patients, there are
      indications that they also have poor pulmonary function. The aim of this study
      was to examine whether patients with chronic neck pain have spirometric
      abnormalities and whether neck pain problems and psychological states are
      associated with these abnormalities. METHODS: Forty-five participants with
      chronic neck pain and 45 well-matched healthy controls were recruited. Spirometry
      was used to assess participants' pulmonary function. Neck muscle strength,
      endurance of deep neck flexors, cervical range of motion, forward head posture,
      psychological states, disability, and pain intensity were also evaluated.
      RESULTS: The results showed that patients with chronic neck pain yielded
      significantly reduced vital capacity, FVC, expiratory reserve volume, and maximum
      voluntary ventilation (P < .05), but peak expiratory flow, FEV1, and FEV1/FVC
      ratio were not affected (P > .05). Strength of neck muscles, pain intensity, and
      kinesiophobia were found to be significantly correlated (r > 0.3, P < .05) with
      respiratory function. CONCLUSIONS: Patients with chronic neck pain do not have
      optimal pulmonary function. Cervical spine muscle dysfunction in parallel with
      pain intensity and kinesiophobia are factors that are associated mainly with this
      respiratory dysfunction.

PMID- 24026192
TI  - Occupational exposure to methylene chloride and risk of cancer: a meta-analysis.
AB  - METHODS: We searched MEDLINE and EMBASE for epidemiologic studies on occupational
      exposure to methylene chloride and risk of cancer. Estimates of study-specific
      odds ratios (ORs) were calculated using inverse-variance-weighted fixed-effects
      models and random-effects models. Statistical tests for heterogeneity were
      applied. RESULTS: We summarized data from five cohort studies and 13 case-control
      studies. The pooled OR for multiple myeloma was (OR 2.04; 95 % CI 1.31-3.17) in
      relation to occupational exposure to methylene chloride but not for non-Hodgkin's
      lymphoma, leukemia, breast, bronchus, trachea and lung, brain and other CNS,
      biliary passages and liver, prostate, pancreas, and rectum. Furthermore, we
      focused on specific outcomes for non-Hodgkin's lymphoma and multiple myeloma
      because of exposure misclassification. The pooling OR for non-Hodgkin's lymphoma
      and multiple myeloma was 1.42 (95 % CI 1.10-1.83) with moderate degree of
      heterogeneity among the studies (I (2) = 26.9 %, p = 0.205). CONCLUSIONS: We
      found an excess risk of multiple myeloma. The non-Hodgkin's lymphoma and leukemia
      that have shown weak effects should be investigated further.

PMID- 24026193
TI  - Viscoelastic properties of the P17 and adult rat brain from indentation in the
      coronal plane.
AB  - This technical brief serves as an update to our previous work characterizing the
      region-dependence of viscoelastic mechanical properties of the P17 and adult rat
      brain in the coronal plane (Elkin et al., 2011, "A Detailed Viscoelastic
      Characterization of the P17 and Adult Rat Brain," J. Neurotrauma, 28, pp. 2235
      2244.). Here, modifications to the microindentation device provided for the
      reliable measurement of load during the ramp portion of load relaxation
      microindentation tests. In addition, a correction factor for finite sample
      thickness was incorporated to more accurately assess the intrinsic mechanical
      properties of the tissue.The shear relaxation modulus was significantly dependent
      on the anatomic region and developmental age, with a general increase in
      stiffness with age and increased stiffness in the hippocampal and cortical
      regions compared with the white matter and cerebellar regions of the brain. The
      shear modulus ranged from ~0.2 kPa to ~2.6 kPa depending on region, age, and time
      scale. Best-fit Prony series parameters from least squares fitting to the
      indentation data from each region are reported, which describe the shear
      relaxation behavior for each anatomic region within each age group at both short
      (<10 ms) and long (~20 s) time scales. These data will be useful for improving
      the biofidelity of finite element models of rat brain deformation at short time
      scales, such as models of traumatic brain injury. 

PMID- 24026194
TI  - MORPHOMETRY FOR EARLY MONITORING OF TREATMENT RESPONSE IN RHEUMATOID ARTHRITIS.
AB  - New aggressive therapeutic options have recently become available to treat
      inflammatory arthritis (IA) and rheumatoid arthritis in particular. These
      treatments not only control joint destruction, they may also aid in new bone
      formation at sites of eroded bone. Separation of non-responders from responders
      to these treatments, is critical, and is known to lead to reduced disease burden,
      toxicity, side-effects and overall cost. The bones of the wrist are early targets
      of IA and are known to show response to therapy early. In this paper, we develop
      a method to quantify point-wise erosive changes of wrist bones in IA patients
      undergoing treatment. The method employs 3D registration-based morphometric
      analysis. Our results indicate that the proposed method has potential to improve
      sensitivity to small, early changes in bone erosion status. This study has
      potential to provide new imaging biomarkers to be used in clinical trials
      evaluating the efficacy of new arthritis drugs.

PMID- 24026195
TI  - Human copper chaperone for superoxide dismutase 1 mediates its own oxidation
      dependent import into mitochondria.
AB  - Oxidative stress is counteracted by various cellular systems, including copper
      zinc superoxide dismutase 1 (SOD1) and its activating chaperone, that is, the
      copper chaperone for SOD1 (CCS1). Both enzymes are structurally related, and both
      localize to the cytosol and the mitochondrial intermembrane space where they
      specifically counteract mitochondria-derived superoxide. The mechanism by which
      human CCS1 is transported into mitochondria is largely unclear. Here we show that
      CCS1 import depends on the presence of mature CCS1 in the mitochondria. During
      import, a disulphide bond is formed in CCS1 in a CCS1-dependent reaction. We
      demonstrate that oxidation and import depend on the presence of cysteine residues
      at positions 227 and 141/144 in CCS1. Notably, CCS1 import parallels SOD1 import
      that also depends on CCS1. Our observations suggest that CCS1 serves as a
      specialized import receptor in mitochondria that facilitates the import and
      folding of SOD1 and CCS1, thereby extending the substrate spectrum of oxidation
      dependent protein import in the mitochondrial intermembrane space. 

PMID- 24026196
TI  - Cystic duct with no visible signal on magnetic resonance cholangiography is
      associated with laparoscopic difficulties: an analysis of 695 cases.
AB  - BACKGROUND/AIMS: We investigated the association between the magnetic resonance
      cholangiography (MRC) results and surgical difficulties and bile duct injuries
      during laparoscopic cholecystectomy (LC). METHODS: MRC was performed on 695
      consecutive patients before LC. We divided the patients into two groups (visible
      cystic duct group and "no signal" cystic duct on MRC group) and compared them
      with regard to the length of the operation, conversion rate to open
      cholecystectomy (OC) and rate of bile duct injury. RESULTS: The "no signal"
      cystic duct on MRC group had a longer operation and higher rate of conversion to
      OC compared with the visible cystic duct group. However, there was no
      statistically significant difference in the occurrence rate of bile duct injury
      between the two groups. CONCLUSIONS: The "no signal" cystic duct on MRC group was
      associated with laparoscopic difficulties, but not with an increased rate of
      biliary injury. When a visible cystic duct is not observed on MRC an early
      conversion to open surgery may avoid a bile duct injury during LC.

PMID- 24026197
TI  - Truncal vagotomy temporarily decreases the pro- and anti-inflammatory cytokine
      levels in the small intestine.
AB  - PURPOSE: The vagus nerve exerts immunomodulatory functions by inhibiting pro
      inflammatory cytokine overproduction. Because vagotomy is a standard procedure
      during the radical operation for esophageal or gastric cancer, the postoperative
      clinical course might be related to vagotomy-associated changes in the cytokine
      milieu. We herein examined the gut cytokine kinetics after vagotomy in mice.
      METHODS: Thirty-eight male Institute of Cancer Research mice underwent sham or
      sub-diaphragmatic truncal vagotomy. The whole small intestine was harvested on
      postoperative day (POD) 14 (sham: vagotomy, n = 9:10) or 20 (n = 9:10). The pro-
      and anti-inflammatory cytokine levels in the plasma, jejunum, ileum and whole
      small intestine were evaluated. RESULTS: The plasma cytokine levels were similar
      in the vagotomy and sham groups on POD 14 and 20. However, both the pro- and anti
      inflammatory cytokine levels tended to be lower on POD 14 and higher on POD 20 in
      the vagotomy group than in the sham group. With regard to the cytokine kinetics,
      the jejunal IL-12p70, TNF-alpha, MCP-1 and IL-10, ileal IL-12p70, TNF-alpha, IL
      6, MCP-1 and IL-10, and whole small intestinal IL-12p70, TNF-alpha, IFN-gamma,
      MCP-1 and IL-10 of the vagotomy group all significantly increased on POD 20 as
      compared to POD 14. CONCLUSION: Vagotomy has a major impact on the gut cytokine
      milieu. Vagotomy may initially inhibit both pro- and anti-inflammatory cytokine
      production, while both later increase.

PMID- 24026198
TI  - Treatment of the postoperative recurrence of lung cancer in octogenarians.
AB  - PURPOSE: Guidelines for the treatment of postoperative recurrent lung cancer in
      octogenarians do not exist. In this study, we investigated the prognosis of
      patients with recurrence after the resection of lung cancer and discuss the
      management of recurrent tumors in octogenarians. METHODS: This study
      clinicopathologically evaluated 135 octogenarians who underwent resections for
      lung cancer at a single institution between 1992 and 2010. We retrospectively
      reviewed the clinical records of 37 patients with confirmed recurrence. The
      overall survival of the patients and the treatments used for postoperative
      recurrence were evaluated. RESULTS: Among 37 patients, six underwent intensive
      treatment, 14 underwent palliative treatment and 17 received supportive care
      only. The overall survival rates of the patients in the antitumor treatment
      groups tended to be associated with a better prognoses than those of the patients
      in the supportive care only group, but they did not exhibit significantly better
      prognoses at 1 year (p = 0.202). However, among the patients with a good
      performance status, the intensive treatment group tended to exhibit prolonged
      survival. Of the 37 patients with recurrent tumors, five (14%) died of other
      diseases. CONCLUSIONS: Antitumor treatment of postoperative recurrent lung cancer
      in octogenarians may not always improve the survival rate. However, carefully
      selecting patients for intensive therapy, such as those with a good performance
      status, may lead to longer survival rates after postoperative recurrence in
      octogenarians.

PMID- 24026199
TI  - RAB38 confers a poor prognosis, associated with malignant progression and subtype
      preference in glioma.
AB  - RAB38 is a new member of the RAB small G protein family that regulates
      intracellular vesicle trafficking. RAB38 is expressed in melanocytes and it has
      been shown that a point mutation in the postulated GTP-binding domain of RAB38 is
      the gene responsible for human Hermansky-Pudlak syndrome. However, the prognostic
      and molecular features of tumors with RAB38 expression is still unclear, as well
      as glioma. Whole genome mRNA expression microarray data on 220 glioma samples
      from the Chinese glioma genome atlas (CGGA) database (http://www.cgga.org.cn) was
      applied as discovery set. Each grade of glioma patients was analyzed by the
      Kaplan-Meier method. To determine the protein expression levels of RAB38, further
      82 glioma tissues were stained by immunohistochemistry. Three additional datasets
      (TCGA, GSE16011 and Rembrandt) were obtained as validation sets. The functional
      annotation of RAB38 was analyzed by Gene ontology (GO) analysis and Gene set
      variation analysis (GSVA) in 89 glioblastomas (GBMs). High RAB38 expression was
      mainly increased in high-grade gliomas, and high RAB38 expression also conferred
      high mortality of glioma in the CGGA cohort. RAB38 showed a mesenchymal subtype,
      G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference. GO and
      GSVA analysis showed that RAB38 was significantly correlated with migration.
      These results were validated in other 3 datasets. The expression levels of RAB38
      were significantly associated with grade progression as well as prognosis in
      gliomas. RAB38 is an important prognostic biomarker and potential therapeutic
      target in gliomas. 

PMID- 24026200
TI  - Troglitazone upregulates PTEN expression and induces the apoptosis of pulmonary
      artery smooth muscle cells under hypoxic conditions.
AB  - The increased proliferation and decreased apoptosis of pulmonary artery smooth
      muscle cells (PASMCs) are the main causes of hypoxic pulmonary hypertension. In
      this study, we investigated the role of troglitazone [peroxisome proliferator
      activated receptor gamma (PPARgamma) agonist] in the regulation of phosphatase
      and tensin homologue deleted on chromosome 10 (PTEN) expression and the apoptosis
      of PASMCs under hypoxic conditions. Normal human PASMCs were cultured in growth
      medium (GM) and treated with troglitazone (0.5-80 uM) under hypoxic conditions
      (5% CO2+94% N2+1% O2) for 72 h. The gene expression of PTEN, AKT-1 and AKT-2 was
      determined by quantitative reverse transcription PCR (qRT-PCR). The protein
      expression level of PTEN, AKT and phosphorylated AKT (p-AKT) was determined by
      western blot analysis. The apoptosis of PASMCs was determined by measuring the
      activities of caspase-3, -8 and -9 and by TUNEL assay. The proliferation rate of
      the PASMCs was altered in a concentration-dependent manner by troglitazone. A
      significantly reduced proliferation rate was observed at troglitazone
      concentrations starting from 20 uM under hypoxic conditions (72 +/- 5.8%).
      Although the gene expression levels of PTEN were increased, the gene expression
      levels of AKT-1 and AKT-2 remained unaltered. Consistent with this, PTEN protein
      expression was also altered in a concentration-dependent manner by troglitazone.
      Although AKT expression was unaltered in all the cell samples, reduced p-AKT
      expression was observed in the troglitazone-treated PASMCs. Troglitazone
      increased the activities of caspase-3, -8 and -9 in the PASMCs. bpV(HOpic) (PTEN
      inhibitor) and GW9662 (PPARgamma inhibitor) inhibited PTEN protein expression and
      recovered the proliferation rate of the PASMCs. TUNEL assay demonstrated that
      troglitazone significantly increased the apoptosis of PASMCs under hypoxic
      conditions. In conclusion, troglitazone increases PTEN expression under hypoxic
      conditions in a concentration-dependent manner. Troglitazone increases the
      apoptosis of PASMCs under hypoxic conditions. The increase in PTEN expression is
      mediated through the PPARgamma signaling pathway.

PMID- 24026201
TI  - Principal component analysis to assess the efficiency and mechanism for enhanced
      coagulation of natural algae-laden water using a novel dual coagulant system.
AB  - A novel dual coagulant system of polyaluminum chloride sulfate (PACS) and
      polydiallyldimethylammonium chloride (PDADMAC) was used to treat natural algae
      laden water from Meiliang Gulf, Lake Taihu. PACS (Aln(OH)mCl3n-m-2k(SO4)k) has a
      mass ratio of 10 %, a SO4 (2-)/Al3 (+) mole ratio of 0.0664, and an OH/Al mole
      ratio of 2. The PDADMAC ([C8H16NCl]m) has a MW which ranges from 5 * 10(5) to 20
      * 10(5) Da. The variations of contaminants in water samples during treatments
      were estimated in the form of principal component analysis (PCA) factor scores
      and conventional variables (turbidity, DOC, etc.). Parallel factor analysis
      determined four chromophoric dissolved organic matters (CDOM) components, and PCA
      identified four integrated principle factors. PCA factor 1 had significant
      correlations with chlorophyll-a (r=0.718), protein-like CDOM C1 (0.689), and C2
      (0.756). Factor 2 correlated with UV254 (0.672), humic-like CDOM component C3
      (0.716), and C4 (0.758). Factors 3 and 4 had correlations with NH3-N (0.748) and
      T-P (0.769), respectively. The variations of PCA factors scores revealed that
      PACS contributed less aluminum dissolution than PAC to obtain equivalent removal
      efficiency of contaminants. This might be due to the high cationic charge and pre
      hydrolyzation of PACS. Compared with PACS coagulation (20 mg L(-1)), the removal
      of PCA factors 1, 2, and 4 increased 45, 33, and 12 %, respectively, in combined
      PACS-PDADMAC treatment (0.8 mg L(-1) +20 mg L(-1)). Since PAC contained more Al
      (0.053 g/1 g) than PACS (0.028 g/1 g), the results indicated that PACS
      contributed less Al dissolution into the water to obtain equivalent removal
      efficiency.

PMID- 24026202
TI  - Copper (II) adsorption by the extracellular polymeric substance extracted from
      waste activated sludge after short-time aerobic digestion.
AB  - The extracellular polymeric substance (EPS) extracted from waste activated sludge
      (WAS) after short-time aerobic digestion was investigated to be used as a novel
      biosorbent for Cu(2+) removal from water. The EPS consisted of protein (52.6 %,
      w/w), polysaccharide (30.7 %, w/w), and nucleic acid (16.7 %, w/w). Short-time
      aerobic digestion process of WAS for about 4 h promoted the productivity growth
      of the EPS for about 10 %. With a molecular weight of about 1.9 * 10(6) Da, the
      EPS showed a linear structure with long chains, and contained carboxyl, hydroxyl,
      and amino groups. The sorption kinetics was well fit for the pseudo-second-order
      model, and the maximum sorption capacity of the EPS (700.3 mg Cu(2+)/g EPS) was
      markedly greater than those of the reported biosorbents. Both Langmuir model and
      Freundlich model commendably described the sorption isotherm. The Gibbs free
      energy analysis of the adsorption showed that the sorption process was feasible
      and spontaneous. According to the complex results of multiple analytical
      techniques, including scanning electron microscopy, Fourier transform infrared
      spectroscopy, atomic force microscopy, etc., the adsorption process took place
      via both physical and chemical sorption, but the electrostatic interaction
      between sorption sites with the functional groups and Cu(2+) is the major
      mechanism.

PMID- 24026203
TI  - Bioaccumulation and the soil factors affecting the uptake of arsenic in
      earthworm, Eisenia fetida.
AB  - To better understand arsenic (As) bioaccumulation, a soil invertebrate species
      was exposed to 17 field soils contaminated with arsenic due to mining activity.
      Earthworms (Eisenia fetida) were kept in the soils for 70 days under laboratory
      conditions, as body burden increased and failed to reach equilibrium in all
      soils. After 70 days of exposure, XANES spectra determined that As was
      biotransformed to a highly reduced form. Uptake kinetics for As was calculated
      using one compartment model. Stepwise multiple regression suggested that sorbed
      As in soils are bioaccessible, and uptake is governed by soil properties (iron
      oxide, sulfate, and dissolved organic carbon) that control As mobility in soils.
      As in soil solution are highly related to uptake rate except four soils which had
      relatively high chloride or phosphate. The results imply that uptake of As is
      through As interaction with soil characteristics as well as direct from the soil
      solution. Internal validation showed that empirically derived regression
      equations can be used for predicting As uptake as a function of soil properties
      within the range of soil properties in the data set.

PMID- 24026204
TI  - Cork stoppers as an effective sorbent for water treatment: the removal of mercury
      at environmentally relevant concentrations and conditions.
AB  - The technical feasibility of using stopper-derived cork as an effective
      biosorbent towards bivalent mercury at environmentally relevant concentrations
      and conditions was evaluated in this study. Only 25 mg/L of cork powder was able
      to achieve 94 % of mercury removal for an initial mercury concentration of 500
      MUg/L. It was found that under the conditions tested, the efficiency of mercury
      removal expressed as equilibrium removal percentage does not depend on the amount
      of cork or its particle size, but is very sensitive to initial metal
      concentration, with higher removal efficiencies at higher initial concentrations.
      Ion exchange was identified as one of the mechanisms involved in the sorption of
      Hg onto cork in the absence of ionic competition. Under ionic competition,
      stopper-derived cork showed to be extremely effective and selective for mercury
      in binary mixtures, while in complex matrices like seawater, moderate inhibition
      of the sorption process was observed, attributed to a change in mercury
      speciation. The loadings achieved are similar to the majority of literature
      values found for other biosorbents and for other metals, suggesting that cork
      stoppers can be recycled as an effective biosorbent for water treatment. However,
      the most interesting result is that equilibrium data show a very rare behaviour,
      with the isotherm presenting an almost square convex shape to the concentration
      axis, with an infinite slope for an Hg concentration in solution around 25 MUg/L.

PMID- 24026205
TI  - Monitoring of polycyclic aromatic hydrocarbons (PAHs) in the atmosphere of
      southern Luxembourg using XAD-2 resin-based passive samplers.
AB  - XAD-2 resin-based passive samplers (PAS) with dimensions adapted to 100 mL
      accelerated solvent extraction cells were used to study the temporal and spatial
      variations of 17 PAHs on five sites in the atmosphere of southern Luxembourg.
      This new design allowed extracting the PAS without emptying the resin from the
      shelter. PAH analyses were done with gas chromatography-tandem mass spectrometry.
      PAS were deployed for 1 year with varying sampling periodicities, and 16 PAHs
      were detected with concentrations ranging from 1 ng/PAS for chrysene to 9,727
      ng/PAS for naphthalene. The PAS were found adapted to the monitoring of temporal
      and spatial variations for lightweight PAHs (up to four aromatic rings) though
      not for heavy PAHs with five aromatic rings or more, as these compounds are
      preferably in the particle phase of the atmosphere and the amount of these PAHs
      trapped on the PAS will be too low.

PMID- 24026206
TI  - Organotin compounds in surface sediments of the Southern Baltic coastal zone: a
      study on the main factors for their accumulation and degradation.
AB  - Sediment samples were collected in the Gulf of Gdansk, and the Vistula and
      Szczecin Lagoons-all located in the coastal zone of the Southern Baltic Sea-just
      after the total ban on using harmful organotins in antifouling paints on ships
      came into force, to assess their butyltin and phenyltin contamination extent.
      Altogether, 26 sampling stations were chosen to account for different potential
      exposure to organotin pollution and environmental conditions: from shallow and
      well-oxygenated waters, shipping routes and river mouths, to deep and anoxic
      sites. Additionally, the organic carbon content, pigment content, and grain size
      of all the sediment samples were determined, and some parameters of the near
      bottom water (oxygen content, salinity, temperature) were measured as well. Total
      concentrations of butyltin compounds ranged between 2 and 182 ng Sn g(-1) d.w.,
      whereas phenyltins were below the detection limit. Sediments from the Gulf of
      Gdansk and Vistula Lagoon were found moderately contaminated with tributyltin,
      whereas those from the Szczecin Lagoon were ranked as highly contaminated.
      Butyltin degradation indices prove a recent tributyltin input into the sediments
      adjacent to sites used for dumping for dredged harbor materials and for anchorage
      in the Gulf of Gdansk (where two big international ports are located), and into
      those collected in the Szczecin Lagoon. Essential factors affecting the
      degradation and distribution of organotins, based on significant correlations
      between butyltins and environmental variables, were found in the study area.

PMID- 24026207
TI  - Environmental photochemistry of fluoroquinolones in soil and in aqueous soil
      suspensions under solar light.
AB  - The photodegradation fate of widely used fluoroquinolone (FQ) drugs has been
      studied both at the water-soil interface and in soil at actual concentrations
      (500 ng g(-1)) under natural solar light. Both human and veterinary drugs have
      been examined, namely ciprofloxacin, danofloxacin, enrofloxacin, levofloxacin,
      marbofloxacin and moxifloxacin. After spiking and irradiation, samples were
      submitted to microwave-assisted extraction and analyzed by high-performance
      liquid chromatography coupled to fluorescence detection (HPLC-FD). FQs
      degradation was faster in aqueous soil suspension than in neat soil (but lower
      than in "clean" water). A number of byproducts were identified by HPLC
      electrospray ionization tandem mass spectrometry after a post-extraction cleanup
      based on a molecularly imprinted polymer phase, for a more accurate detection.
      The distribution in the suspension was intermediate between those observed in
      soils and in aqueous solutions.

PMID- 24026208
TI  - Influence of microbial and synthetic surfactant on the biodegradation of
      atrazine.
AB  - The present study reports the effect of surfactants (rhamnolipids and triton X
      100) on biodegradation of atrazine herbicide by strain A6, belonging to the genus
      Acinetobacter. The strain A6 was able to degrade nearly 80 % of the 250-ppm
      atrazine after 6 days of growth. The bacterium degraded atrazine by de-alkylation
      process. Bacterial cell surface hydrophobicity as well as atrazine solubility
      increased in the presence of surfactant. However, addition of surfactant to the
      mineral salt media reduced the rate and extent of atrazine degradation by
      decreasing the bioavailability of herbicide. On the contrary, addition of
      surfactant to atrazine-contaminated soil increased the rate and extent of
      biodegradation by increasing the bioavailability of herbicide. As compared to
      triton X-100, rhamnolipids were more efficient in enhancing microbial degradation
      of atrazine as a significant amount of atrazine was removed from the soil by
      rhamnolipids. Surfactants added for the purpose of hastening microbial
      degradation may have an unintended inhibitory effect on herbicide degradation
      depending upon contiguous condition, thus highlighting the fact that surfactant
      must be judiciously used in bioremediation of herbicides.

PMID- 24026209
TI  - Strategies to evaluate biodegradability: application to chlorinated herbicides.
AB  - The biodegradability of nitrochlorinated (diuron and atrazine) and chlorophenoxy
      herbicides (2,4-D and MCPA) has been studied through several bioassays using
      different testing times and biomass/substrate ratios. A fast biodegradability
      test using unacclimated activated sludge yielded no biodegradation of the
      herbicides in 24 h. The inherent biodegradability test gave degradation
      percentages of around 20-30% for the nitrochlorinated herbicides and almost
      complete removal of the chlorophenoxy compounds. Long-term biodegradability
      assays were performed using sequencing batch reactor (SBR) and sequencing batch
      membrane bioreactor (SB-MBR). Fixed concentrations of each herbicide below the
      corresponding EC50 value for activated sludge were used (30 mg L(-1) for diuron
      and atrazine and 50 mg L(-1) for 2,4-D and MCPA). No signs of herbicide
      degradation appeared before 35 days in the case of diuron and atrazine and 21
      days for 2,4-D, whereas MCPA was partially degraded since the early stages.
      Around 25-36% degradation of the nitrochlorinated herbicides and 53-77% of the
      chlorophenoxy ones was achieved after 180 and 135 days, respectively, in SBR,
      whereas complete disappearance of 2,4-D was reached after 80 days in SB-MBR.

PMID- 24026210
TI  - The BRAF V600K mutation is more frequent than the BRAF V600E mutation in melanoma
      in situ of lentigo maligna type.

PMID- 24026212
TI  - Impact of impaired insulin secretion and insulin resistance on the incidence of
      diabetes in a Japanese cohort.

PMID- 24026213
TI  - Mouse beta cell proliferation is inhibited by thymidine analogue labelling.
AB  - AIMS/HYPOTHESIS: Long-term labelling of mice with halogenated thymidine analogues
      is an established method for quantifying the contribution of beta cell
      proliferation to in vivo beta cell mass expansion in (re)generation models. The
      method is believed to give accurate information on the accrued number of cycling
      beta cells over a period of time. Multiple thymidine analogue labelling is
      applied for evaluating the duration of postmitotic quiescence in beta cells. We
      hypothesise, however, that long-term labelling by thymidine analogues hampers
      beta cell proliferation. METHODS: Thymidine analogues were administered for 7-14
      days via the i.p. route to neonatal mice, or via drinking water to young mice
      with normal pancreases or adult mice with injured pancreases. The proliferation
      of insulin-positive cells was assessed by their expression of the proliferation
      markers Ki67 or phosphorylated histone H3 and by their incorporation of
      nucleotide analogues. RESULTS: In the mouse models of beta cell proliferation
      investigated herein, long-term administration of thymidine analogues decreased
      the percentage of Ki67(+) and phosphorylated histone H3(+) beta cells as compared
      with administration of normal drinking water. Proliferation was restored by
      washout of the analogue. Labelling with one analogue decreased the subsequent
      incorporation of another analogue by beta cells. CONCLUSIONS/INTERPRETATION: Long
      term labelling with halogenated thymidine analogues is a biased method that
      underestimates the proliferation and re-division potential of mouse beta cells.

PMID- 24026211
TI  - Efficacy and safety of canagliflozin compared with placebo and sitagliptin in
      patients with type 2 diabetes on background metformin monotherapy: a randomised
      trial.
AB  - AIMS/HYPOTHESIS: The aim of this work was to evaluate the efficacy and safety of
      canagliflozin vs placebo and sitagliptin in patients with type 2 diabetes who
      were being treated with background metformin. METHODS: This randomised, double
      blind, four-arm, parallel-group, Phase 3 study was conducted at 169 centres in 22
      countries between April 2010 and August 2012. Participants (N = 1,284) with type
      2 diabetes aged >= 18 and <= 80 years who had inadequate glycaemic control (HbA1c
      >= 7.0% [53 mmol/mol] and <=10.5% [91 mmol/mol]) on metformin therapy received
      canagliflozin 100 mg or 300 mg, sitagliptin 100 mg, or placebo (n = 368, 367,
      366, 183, respectively) for a 26 week, placebo- and active-controlled period
      followed by a 26 week, active-controlled period (placebo group switched to
      sitagliptin [placebo/sitagliptin]) and were included in the modified intent-to
      treat analysis set. Randomisation was performed using a computer-generated
      schedule; participants, study centres and the sponsor were blinded to group
      assignment. The primary endpoint was change from baseline in HbA1c at week 26;
      secondary endpoints included changes in HbA1c (week 52) and fasting plasma
      glucose (FPG), body weight, and systolic blood pressure (BP; weeks 26 and 52).
      Adverse events (AEs) were recorded throughout the study. RESULTS: At week 26,
      canagliflozin 100 mg and 300 mg reduced HbA1c vs placebo (-0.79%, -0.94%, -0.17%,
      respectively; p < 0.001). At week 52, canagliflozin 100 mg and 300 mg
      demonstrated non-inferiority, and canagliflozin 300 mg demonstrated statistical
      superiority, to sitagliptin in lowering HbA1c (-0.73%, -0.88%,-0.73%,
      respectively); differences (95% CI) vs sitagliptin were 0% (-0.12, 0.12) and 
      0.15% (-0.27, -0.03), respectively. Canagliflozin 100 mg and 300 mg reduced body
      weight vs placebo (week 26: -3.7%, -4.2%, -1.2%, respectively; p < 0.001) and
      sitagliptin (week 52: -3.8%, -4.2%, -1.3%, respectively; p < 0.001). Both
      canagliflozin doses reduced FPG and systolic BP vs placebo (week 26) and
      sitagliptin (week 52) (p < 0.001). Overall AE and AE-related discontinuation
      rates were generally similar across groups, but higher with canagliflozin 100 mg.
      Genital mycotic infection and osmotic diuresis-related AE rates were higher with
      canagliflozin; few led to discontinuations. Hypoglycaemia incidence was higher
      with canagliflozin. CONCLUSIONS/INTERPRETATION: Canagliflozin improved glycaemia
      and reduced body weight vs placebo (week 26) and sitagliptin (week 52) and was
      generally well tolerated in patients with type 2 diabetes on metformin. CLINICAL
      TRIAL REGISTRY: ClinicalTrials.gov NCT01106677 FUNDING: This study was supported
      by Janssen Research & Development, LLC.

PMID- 24026214
TI  - Airway pressure release ventilation prevents ventilator-induced lung injury in
      normal lungs.
AB  - IMPORTANCE: Up to 25% of patients with normal lungs develop acute lung injury
      (ALI) secondary to mechanical ventilation, with 60% to 80% progressing to acute
      respiratory distress syndrome (ARDS). Once established, ARDS is treated with
      mechanical ventilation that can paradoxically elevate mortality. A ventilation
      strategy that reduces the incidence of ARDS could change the clinical paradigm
      from treatment to prevention. OBJECTIVES: To demonstrate that (1) mechanical
      ventilation with tidal volume (VT) and positive end-expiratory pressure (PEEP)
      settings used routinely on surgery patients causes ALI/ARDS in normal rats and
      (2) preemptive application of airway pressure release ventilation (APRV) blocks
      drivers of lung injury (ie, surfactant deactivation and alveolar edema) and
      prevents ARDS. DESIGN, SETTING, AND SUBJECTS: Rats were anesthetized and
      tracheostomy was performed at State University of New York Upstate Medical
      University. Arterial and venous lines, a peritoneal catheter, and a rectal
      temperature probe were inserted. Animals were randomized into 3 groups and
      followed up for 6 hours: spontaneous breathing ventilation (SBV, n = 5),
      continuous mandatory ventilation (CMV, n = 6), and APRV (n = 5). Rats in the CMV
      group were ventilated with Vt of 10 cc/kg and PEEP of 0.5 cm H2O. Airway pressure
      release ventilation was set with a P(High) of 15 to 20 cm H2O; P(Low) was set at
      0 cm H2O. Time at P(High) (T(High)) was 1.3 to 1.5 seconds and a T(Low) was set
      to terminate at 75% of the peak expiratory flow rate (0.11-0.14 seconds),
      creating a minimum 90% cycle time spent at P(High). Bronchoalveolar lavage fluid
      and lungs were harvested for histopathologic analysis at necropsy. RESULTS: Acute
      lung injury/ARDS developed in the CMV group (mean [SE] PaO2/FiO2 ratio, 242.96
      [24.82]) and was prevented with preemptive APRV (mean [SE] PaO2/FIO2 ratio,
      478.00 [41.38]; P < .05). Airway pressure release ventilation also significantly
      reduced histopathologic changes and bronchoalveolar lavage fluid total protein
      (endothelial permeability) and preserved surfactant proteins A and B
      concentrations as compared with the CMV group. CONCLUSIONS AND RELEVANCE:
      Continuous mandatory ventilation in normal rats for 6 hours with Vt and PEEP
      settings similar to those of surgery patients caused ALI. Preemptive application
      of APRV blocked early drivers of lung injury, preventing ARDS. Our data suggest
      that APRV applied early could reduce the incidence of ARDS in patients at risk.

PMID- 24026215
TI  - Communication disruption of guava moth (Coscinoptycha improbana) using a
      pheromone analog based on chain length.
AB  - The guava moth, Coscinoptycha improbana, an Australian species that infests fruit
      crops in commercial and home orchards, was first detected in New Zealand in 1997.
      A four-component pheromone blend was identified but is not yet commercially
      available. Using single sensillum recordings from male antennae, we established
      that the same olfactory receptor neurons responded to two guava moth sex
      pheromone components, (Z)-11-octadecen-8-one and (Z)-12-nonadecen-9-one, and to a
      chain length analog, (Z)-13-eicosen-10-one, the sex pheromone of the related
      peach fruit moth, Carposina sasakii. We then field tested whether this non
      specificity of the olfactory neurons might enable disruption of sexual
      communication by the commercially available analog, using male catch to synthetic
      lures in traps in single-tree, nine-tree and 2-ha plots. A disruptive pheromone
      analog, based on chain length, is reported for the first time. Trap catches for
      guava moth were disrupted by three polyethylene tubing dispensers releasing the
      analog in single-tree plots (86% disruption of control catches) and in a plots of
      nine trees (99% disruption). Where peach fruit moth pheromone dispensers were
      deployed at a density of 1000/ha in two 2-ha areas, pheromone traps for guava
      moth were completely disrupted for an extended period (up to 470 days in peri
      urban gardens in Mangonui and 422 days in macadamia nut orchards in Kerikeri). In
      contrast, traps in untreated areas over 100 m away caught 302.8 +/- 128.1
      moths/trap in Mangonui and 327.5 +/- 78.5 moths/ trap in Kerikeri. The longer
      chain length in the pheromone analog has greater longevity than the natural
      pheromone due to its lower volatility. Chain length analogs may warrant further
      investigation for mating disruption in Lepidoptera, and screening using single
      sensillum recording is recommended.

PMID- 24026216
TI  - Dual mobility cup: dislocation rate and survivorship at ten years of follow-up.
AB  - PURPOSE: The dual mobility cup introduced in France by Gilles Bousquet has been
      used in total hip replacement in high-risk patients. This device acts as a large
      ball implant and significantly reduces the risk of dislocation following hip
      arthroplasty. Published French literature has focused on low rates of dislocation
      and long-term follow-up similar to the low-friction arthroplasty. METHODS: We
      retrospectively reviewed a continuous series of 105 cases of dual mobility cup
      Quattro (Groupe Lepine, Genay, France) implanted from 2000 to 2002. Selection of
      the patients requiring a primary hip replacement depended on risk criteria such
      as age, hip disease and activity score. The dual mobility cup was associated with
      a modular cemented femoral component and a 22.2-mm stainless steel head. RESULTS:
      One dislocation occurred one month after the index surgery requiring no revision
      surgery. According to the Kaplan-Meier method, survival probability was 95.0%
      (95% confidence interval 81.5-98.8) at ten years of follow-up. CONCLUSIONS: Based
      on clinical outcome and patient assessment we conclude that the dual mobility cup
      is a reliable option to decrease dislocation risk without increasing polyethylene
      wear.

PMID- 24026217
TI  - Prevalence of osteoarthritis and clinical results after the Elmslie-Trillat
      procedure: a retrospective long-term follow-up.
AB  - PURPOSE: Tibial tuberosity medialisation may be followed by osteoarthritis in the
      long term due to increased patellofemoral contact pressure and altered knee joint
      kinematics. We aimed to (1) systematically assess the grades of tibiofemoral and
      patellofemoral osteoarthritis ten to 30 years after the Elmslie-Trillat procedure
      and (2) to evaluate long-term knee function and activities of daily living.
      METHODS: A total of 26 patients (30 knees) were re-evaluated at a minimum follow
      up of 12.3 years (mean 20.9 +/- 4.1 years). Osteoarthritis was graded according
      to Kellgren and Lawrence (K/L) and Sperner. All patients were clinically
      evaluated using the Knee Society Score (KSS) and Knee injury and Osteoarthritis
      Outcome Score (KOOS). Radiographic data were compared to an age-, sex- and body
      mass index-matched control group of healthy patients. RESULTS: Radiographic
      evaluation revealed seven cases (23.3%) with advanced osteoarthritis (K/L and
      Sperner grades 3 and 4). However, the observed differences from the matched
      cohort were not statistically significant (P = 0.189). A positive correlation was
      found between the age at index procedure and tibiofemoral osteoarthritis at
      follow-up (P = 0.013). Patient satisfaction was relatively high, showing a mean
      KSS of 89.9 (knee score) and 94.8 (function score), and a mean KOOS of 78.7.
      However, we noted four cases of frequent patellar re-dislocations and three total
      knee arthroplasties. CONCLUSIONS: The Elmslie-Trillat procedure was associated
      with several cases of advanced tibiofemoral and patellofemoral osteoarthritis in
      the long term, especially if the procedure was performed late. Clinical results
      were still good to excellent in the majority of patients despite some observed
      cases of re-dislocations and decreased ability to perform sports.

PMID- 24026218
TI  - Posterior acetabular arc angle of unstable posterior hip fracture-dislocation.
AB  - PURPOSE: Posterior hip fracture-dislocation needs stability evaluation. A
      previous study in the normal acetabulum has shown that the coronal posterior
      acetabular arc angle (PAAA) could be used to assess an unstable posterior hip
      fracture. Our study was designed to assess PAAA of unstable posterior hip
      fracture-dislocation and whether posterior acetabular wall fracture involves the
      superior acetabular dome. METHODS: Using coronal computed tomography (CT) of the
      acetabulum and 3D reconstruction of the lateral pelvis, we measured coronal,
      vertical PAAA and posterior acetabular wall depth of 21 unstable posterior hip
      fracture-dislocations and of 50% normal contralateral acetabula. Posterior
      acetabular wall fracture was assessed to determine whether the fracture involved
      the superior acetabular dome and then defined as a high or low wall fracture
      using vertical PAAA in reference to the centroacetabulo-greater sciatic notch
      line. RESULTS: The coronal PAAA of unstable posterior hip fracture-dislocations
      and of 50% of the posterior acetabular wall of normal the contralateral
      acetabulum were 54.48 degrees  (9.09 degrees ) and 57.43 degrees  (5.88 degrees )
      and corresponded to 15.06 (4.39) and 15.61 (2.01) mm of the posterior acetabular
      wall without significant difference (p > 0.05). The vertical PAAA of unstable
      posterior hip fracture-dislocation was 101.67 degrees  (20.44 degrees ). There
      were 16 high posterior acetabular wall fractures with 35.00 (16.18) vertical PAAA
      involving the acetabular dome and 5 low wall fractures. High posterior wall
      fractures resulted in four avascular necroses of the femoral head, three sciatic
      nerve injuries and one osteoarthritic hip. CONCLUSION: Coronal and vertical PAAA
      of unstable posterior hip fracture-dislocations were 54.48 degrees  and 101.67
      degrees . Vertical PAAA assesses high or low posterior acetabular wall fracture
      by referring to the centroacetabulo-greater sciatic notch line. High posterior
      wall fracture seems to be the most frequent and is involved with many
      complications.

PMID- 24026219
TI  - Combined anteversion technique reduced the dislocation in cementless total hip
      arthroplasty.
AB  - PURPOSE: The combined anteversion (CA) technique is a method in which the cup is
      placed according to the stem anteversion in total hip arthroplasty (THA). We
      examined whether the CA technique reduced the dislocation rate, and the
      distribution of CA with the manual placement of the cup. METHODS: We
      retrospectively reviewed 634 hips in 579 patients with primary cementless THA. In
      230 hips using the CA technique [CA(+)], a CA of 50 +/- 10 degrees  was the aim.
      In the remaining 404 hips [CA(-)], the cup was first placed targeting 20 degrees 
      of anteversion. The post-operative CA was measured using the computed tomography
      (CT) images in 111 hips. RESULTS: One hip (0.4%) had a dislocation in the CA(+)
      group, whereas ten hips (2.5%) had a dislocation in the CA(-) group. A
      multivariate analysis showed that primary diagnosis, head size and CA technique
      significantly influenced the dislocation rate. Patients in the CA(-) group were
      5.8 times more likely to have a dislocation compared to the CA(+) group. In the
      111 hips with CT images, 81 hips (73.0%) achieved the intended CA. CONCLUSIONS:
      Although the manual placement of the cup resulted in 27% of outliers from the
      intended CA, the CA technique significantly reduced the dislocation after primary
      THA.

PMID- 24026220
TI  - MRI findings in crural compartment syndrome: a case series.
AB  - Compartment syndrome occurs when the pressure inside a closed fascial compartment
      increases to a level that compromises the blood supply to the structures.
      Untreated compartment syndrome commonly leads to muscle necrosis, limb
      amputation, and, if it is severe, which is seen in large compartments, renal
      failure and death may occur. We discussed MRI findings of crural compartment
      syndrome based on the case series. 

PMID- 24026221
TI  - Development of an inertia-driven model of sideways fall for detailed study of
      femur fracture mechanics.
AB  - A new method for laboratory testing of human proximal femora in conditions
      simulating a sideways fall was developed. Additionally, in order to analyze the
      strain state in future cadaveric tests, digital image correlation (DIC) was
      validated as a tool for strain field measurement on the bone of the femoral neck.
      A fall simulator which included models for the body mass, combined lateral femur
      and pelvis mass, pelvis stiffness, and trochanteric soft tissue was designed. The
      characteristics of each element were derived and developed based on human data
      from the literature. The simulator was verified by loading a state-of-the-art
      surrogate femur and comparing the resulting force-time trace to published, human
      volunteer experiments. To validate the DIC, 20 human proximal femora were
      prepared with a strain rosette and speckle paint pattern, and loaded to 50% of
      their predicted failure load at a low compression rate. Strain rosettes were
      taken as the gold standard, and minimum principal strains from the DIC and the
      rosettes were compared using descriptive statistics. The initial slope of the
      force-time curve obtained in the fall simulator matched published human volunteer
      data, with local peaks superimposed in the model due to internal vibrations of
      the spring used to model the pelvis stiffness. Global force magnitude and
      temporal characteristics were within 2% of published volunteer experiments. The
      DIC minimum principal strains were found to be accurate to 127+/-239 MUE. These
      tools will allow more biofidelic laboratory simulation of falls to the side, and
      more detailed analysis of proximal femur failure mechanisms using human cadaver
      specimens.

PMID- 24026222
TI  - Isolated caudate lobectomy with pancreatoduodenectomy for a bile duct cancer.
AB  - BACKGROUND: In patients with distal bile duct cancer involving the hepatic hilus,
      a major hepatectomy concomitant with pancreatoduodenectomy (HPD) is sometimes
      ideal to obtain a cancer-free resection margin. However, the surgical
      invasiveness of HPD is considerable. PATIENTS AND METHODS: We present our
      treatment option for patients with distal bile duct cancer showing mucosal
      spreading to the hepatic hilum associated with impaired liver function. To
      minimize resection volume of the liver, an isolated caudate lobectomy (CL) with
      pancreatoduodenectomy (PD) using an anterior liver splitting approach is
      presented. Liver transection lines and bile duct resection points correspond
      complete with our standard right and left hemihepatectomies with CL for perihilar
      cholangiocarcinoma. RESULTS: Total operation time was 765 min, and pedicle
      occlusion time was 124 min, respectively. Although the proximal mucosal cancer
      extension was identified at both the right and the left hepatic ducts, all
      resection margins were negative for cancer. CONCLUSIONS: Isolated CL with PD is
      an alternative radical treatment option for bile duct cancer patients with
      impaired liver function.

PMID- 24026223
TI  - Alcohol marketing in televised English professional football: a frequency
      analysis.
AB  - AIMS: The aim of the study was to explore the frequency of alcohol marketing
      (both formal commercials and otherwise) in televised top-class English
      professional football matches. METHODS: A purposive sample of six broadcasts
      (total = 1101 min) of televised top-class English club football matches were
      identified and recorded in full. A customized coding framework was used to
      identify and categorize all verbal and visual alcohol references in non
      commercial broadcasting. The number and the duration of all formal alcohol
      commercials were also noted. RESULTS: A mean of 111 visual references and 2
      verbal references to alcohol per hour of broadcast were identified. Nearly all
      visual references were to beer products and were primarily simple logos or
      branding. The majority of verbal alcohol references were related to title
      sponsorship of competitions. A total of 17 formal alcohol commercials were
      identified, accounting for <1% of total broadcast time. CONCLUSION: Visual
      alcohol references in televised top-class English football matches are common
      with an average of nearly two per minute. Verbal references are rare and formal
      alcohol commercials account for <1% of broadcast time. Restriction of all alcohol
      sports sponsorship, as seen for tobacco, may be justified.

PMID- 24026224
TI  - Two-dimensional vanadyl phosphate ultrathin nanosheets for high energy density
      and flexible pseudocapacitors.
AB  - Two-dimensional materials have been an ideal material platform for constructing
      flexible ultrathin-film supercapacitors, offering great advantages of
      flexibility, ultra-thinness and even transparency. Exploring new two-dimensional
      pseudocapacitive materials with high electrochemical activity is needed to
      achieve flexible ultrathin-film supercapacitors with higher energy densities.
      Here we report an inorganic graphene analogue, alpha1-vanadyl phosphate ultrathin
      nanosheets with less than six atomic layers, as a promising material to construct
      a flexible ultrathin-film pseudocapacitor in all-solid-state. The material
      exhibits a high potential plateau of ~ 1.0 V in aqueous solutions, approaching
      the electrochemical potential window of water (1.23 V). The as-established
      flexible supercapacitor achieves a high redox potential (1.0 V) and a high areal
      capacitance of 8,360.5 MUF cm(-2), leading to a high energy density of 1.7 mWh
      cm(-2) and a power density of 5.2 mW cm(-2).

PMID- 24026225
TI  - Self-regulatory depletion enhances neural responses to rewards and impairs top
      down control.
AB  - To be successful at self-regulation, individuals must be able to resist impulses
      and desires. The strength model of self-regulation suggests that when self
      regulatory capacity is depleted, self-control deficits result from a failure to
      engage top-down control mechanisms. Using functional neuroimaging, we examined
      changes in brain activity in response to viewing desirable foods among 31 chronic
      dieters, half of whom completed a task known to result in self-regulatory
      depletion. Compared with nondepleted dieters, depleted dieters exhibited greater
      food-cue-related activity in the orbitofrontal cortex, a brain area associated
      with coding the reward value and liking aspects of desirable foods; they also
      showed decreased functional connectivity between this area and the inferior
      frontal gyrus, a region commonly implicated in self-control. These findings
      suggest that self-regulatory depletion provokes self-control failure by reducing
      connectivity between brain regions that are involved in cognitive control and
      those that represent rewards, thereby decreasing the capacity to resist
      temptations. 

PMID- 24026226
TI  - Cisplatin regulates SH-SY5Y cell growth through downregulation of BDNF via miR
      16.
AB  - Brain-derived neurotropic factor (BDNF) is a member of the neurotropin family.
      High levels of BDNF are associated with more aggressive malignant behavior in
      human cancer. In the present study, we observed the effect of cisplatin on BDNF
      expression in SH-SY5Y cells and investigated the mechanism of cisplatin in
      inducing the apoptosis of SH-SY5Y cells. Our results revealed that the expression
      of BDNF was obviously decreased in cisplatin-treated SH-SY5Y cells. In addition,
      the 3'-untranslated region of BDNF was found to be targeted by miR-16 using
      microRNA analysis software. After miR-16 was synthesized chemically, SH-SY5Y
      cells were transfected with miR-16 to investigate the regulatory role of miR-16
      in regards to BDNF. The results showed that the expression of BDNF was markedly
      decreased in the miR-16-transfected cells when compared with that in the control
      cultures as determined by western blotting. Moreover, miR-16 expression was
      obviously upregulated in the cisplatin-treated cells when compared with the
      untreated controls. Furthermore, SH-SY5Y cells were xenografted subcutaneously in
      nude mice to study the effect of cisplatin on the growth of SH-SY5Y cells in
      vivo. The results further showed that cisplatin inhibited the proliferation of SH
      SY5Y cells in the cisplatin-treated mice when compared with the saline-treated
      control. The expression of miR-16 was increased, while the expression of BDNF was
      decreased in the cisplatin-treated mice. Our results demonstrated that cisplatin
      downregulated the expression of BDNF through miR-16 to inhibit SH-SY5Y cell
      proliferation in vitro and in vivo. These findings provide the basis for new
      targets for drug design or cancer therapy. 

PMID- 24026227
TI  - Imaging pancreas transplants.
AB  - Pancreas transplants are performed in multiple centres across the UK with good
      graft survival rates. This places an increasing demand on radiology services,
      particularly as the complication rates are not insignificant. The imaging
      appearances of pancreas transplants and their complications can be difficult to
      interpret. This review provides an illustrative journey through the anatomical
      appearances of a graft and the imaging appearances of complications, as a
      reference tool for radiologists. 

PMID- 24026228
TI  - Robot-assisted triple neurectomy for iatrogenic inguinal pain: a technical note.
AB  - BACKGROUND: Painful neuromas are a relatively common complication of hernia and
      abdominal wall surgery. OBJECTIVE: Surgical neurectomy has the potential to to
      provide durable relief for chronic pain; however, current surgical approaches are
      not without morbidity or anatomical challenges.We sought a surgical alternative.
      METHODS: In the treatment of a case of incapacitating inguinal pain, we performed
      an anterior transperitoneal approach using a surgical robot. RESULTS: This
      approach was facile and provided elegant anatomical visualization. CONCLUSION:
      This case describes the first known robot-assisted laparoscopic triple neurectomy
      and details a simplified, transperitoneal approach.

PMID- 24026229
TI  - A practical grading system of ultrasonographic visibility for intracerebral
      lesions.
AB  - BACKGROUND: Intraoperative ultrasound for intracranial neurosurgery was largely
      abandoned in the 1980s due to poor image resolution. Despite many technological
      advances in ultrasound since then, the use of this imaging modality in
      contemporary practice remains limited. Our aim was to evaluate the utility of
      modern intraoperative ultrasound in the resection of a wide variety of
      intracranial pathologies. METHODS: A total of 105 patients who underwent
      intracranial lesion resection in a contiguous fashion were prospectively included
      in the study. Ultrasound images acquired intraoperatively were used to stratify
      lesions into one of four grades (grades 0-3) on the basis of their ultrasonic
      echogenicity and border visibility. RESULTS: Forty-two out of 105 lesions (40 %)
      were clearly identifiable and had a clear border with normal tissue (grade 3).
      Fifty-five of 105 lesions (52 %) were clearly identifiable but had no clear
      border with normal tissue (grade 2). Eight of 105 lesions (8 %) were difficult to
      identify and had no clear border with normal tissue (grade 1). None (0 %) of the
      lesions could not be identified (grade 0). High-grade gliomas, cerebral
      metastases, meningiomas, ependymomas, and haemangioblastomas all demonstrated a
      median ultrasonic visibility grade of 2 or greater. Low-grade astrocytomas and
      oligodendrogliomas demonstrated a median ultrasonic visibility grade of 2 or
      less. CONCLUSION: Intraoperative ultrasound can be of tremendous benefit in
      allowing the surgeon to appraise the location, extent, and local environment of
      their target lesion, as well as to reduce the risk of preventable complications.
      We believe that our grading system will provide a useful adjunct to the
      neurosurgeon when deciding for which lesions intraoperative ultrasound would be
      useful.

PMID- 24026230
TI  - Improved outcome of patients with severe thalamic hemorrhage treated with
      cerebrospinal fluid drainage and neurocritical care during 1990-1994 and 2005
      2009.
AB  - INTRODUCTION: Patients with thalamic hemorrhage, depressed level of consciousness
      and/or signs of elevated intracranial pressure may be treated with neurocritical
      care (NCC) and external ventricular drainage (EVD) for release of cerebrospinal
      fluid. METHODS: Forty-three patients with thalamic hemorrhage treated with NCC
      from 1990 to 1994 (n = 21) and from 2005-2009 (n = 22) were evaluated. Outcome
      was assessed using the Glasgow Coma Scale (GCS) score at discharge from our unit
      and the modified Rankin Scale (mRS) for long-term outcome. RESULTS: Patients' age
      was 59.5 +/- 7 years in 1990-1994, and 58.2 +/- 9 years in 2005-2009. The median
      (25th and 75th percentile) GCS score on admission for the two time periods was 9
      (6-12) and 9 (4-14), respectively. Long-term follow-up was assessed at a mean of
      37.1 (range 19-65) months after disease onset for the 1990-1994 cohort and at
      37.4 (range 14-58) months for the 2005-2009 cohort. Compared to patients from
      1990 to 1994, patients from 2005 to 2009 had a significantly better outcome
      (median mRS [25th and 75th percentile]: 5 [4-6] vs. 4 [2-4.5]; p < 0.01). Most
      patients (13/21, 62 %) treated from 1990 to 1994 had unchanged or lower GCS
      scores during their NCC stay in contrast to 7/22 (32 %) from 2005 to 2009. At the
      last follow-up, 13/21 (62 %) patients from 1990 to 1994 were dead in comparison
      to 4/21 (19 %) from 2005 to 2009 (p < 0.05). Negative prognostic factors were the
      120 h post-admission GCS score in the 1990-1994 patient cohort (p = 0.07) and
      high age in the recent cohort (p = 0.04). CONCLUSIONS: Patients with thalamic
      hemorrhage and depressed level of consciousness on admission had a worse outcome
      in the early 1990s compared with the late 2000s, which may at least be partially
      attributed to refined neurocritical care.

PMID- 24026231
TI  - Meningioma surgery in the very old-validating prognostic scoring systems.
AB  - BACKGROUND: Several studies acknowledge a higher risk of morbidity and mortality
      following intracranial meningioma surgery in the elderly, yet there is no
      consensus with regards to risk factors. Four prognostic scoring systems have been
      proposed. To evaluate their usefulness, we assess the very old meningioma
      patients in our neuro-oncological database according to the four methods, and
      correlate the findings with mortality and morbidity. METHODS: We retrospectively
      calculated scores according to the Clinical-Radiological Grading System (CRGS),
      the Sex, Karnofsky Performance Scale, American Society of Anesthesiology Class,
      Location of Tumor, and Peritumoral Edema grading system (SKALE), the Geriatric
      Scoring System (GSS) and the Charlson Comorbidity Index (CCI) from all patients
      aged 80-90 years who had primary surgery for intracranial meningiomas 2003-2013
      (n = 51), and related our findings to morbidity and mortality. RESULTS: The
      mortality rates were 3.9 %, 5.9 % and 15.7 % at 30-days, 3-months and 1-year post
      surgery. The rate of complications requiring surgery was 13.7 %, 5.9 % had
      evacuation of intracerebral hematomas and two patients (3.9 %) had surgery for
      intracranial infection/osteitis. 15.7 % of the patients were neurologically
      worsened on discharge. The patients with SKALE scores <= 8 had significantly
      increased mortality rates. The GSS, the CRGS and the CCI were not found to
      correlate with mortality. CONCLUSIONS: Retrospectively evaluating four proposed
      scoring systems, we find that the SKALE score reflects the mortality at 1 month
      and 1 year following primary surgery for intracranial meningiomas in our very old
      patients. It may represent a helpful adjunct to their preoperative assessment.

PMID- 24026232
TI  - Infection surveillance in transsphenoidal pituitary surgery - comparison of
      lipopolysaccharide-binding-protein, interleukin 6, C-reactive protein, white
      blood cell count, erythrocyte sedimentation rate and body temperature.
AB  - BACKGROUND: One of the major concerns in transsphenoidal surgery are infections
      because the approach to the pituitary includes a route of microbial colonization.
      To minimize the associated morbidity and mortality, a surveillance program is
      crucial to monitor for perioperative infections. METHODS: For 1 year, we analysed
      body temperature (BT), erythrocyte sedimentation rate (ESR), white blood cell
      count (WBC), C-reactive protein (CRP), interleukin 6 (IL-6) and
      lipopolysaccharide-binding-protein (LBP) following elective transsphenoidal
      pituitary surgery. Samples were collected on admission, day 1, 3 and 7 as well as
      3 months postoperatively. RESULTS: In 116 patients, all data were available. No
      postoperative infections occurred within the first postoperative week. BT (37.6
      +/- 0.6, baseline 37.0 +/- 0.5  degrees C), WBC (11,366 +/- 2,541, baseline 6,861
      +/- 2,123/MUl), CRP (25.3 +/- 22.6, baseline 3.1 +/- 6 mg/l), IL-6 (12 +/- 13,
      baseline 2.7 +/- 2.6 pg/ml), and LBP (11.3 +/- 4.9, baseline 5.7 +/- 2.7 MUg/ml)
      peaked on day 1 postoperatively (each p = 0.001), while ESR peaked on day 3 (25
      +/- 16, baseline 13 +/- 11 mm/h, p = 0.001). BT and IL-6 normalized by day 3 and
      CRP by day 7, while ESR (23 +/- 16 mm/h, p = 0.001), WBC (7,807 +/- 2,750/MUl, p
      = 0.001) and LBP (7.3 +/- 2.6 MUg/ml, p = 0.028) were still increased by day 7.
      CONCLUSION: The present study establishes normative values for an infection
      surveillance following transsphenoidal pituitary surgery. CRP, a convenient and
      reasonable priced parameter, is affected by the procedure for the first
      postoperative week. IL-6 is more robust and allows a close monitoring on the
      expense of additional pricing. ESR, WBC and LBP are sustained affected by
      surgery, and do not offer any advantage. Since no infections were observed, we
      were unable to calculate the respective sensitivity and specificity.

PMID- 24026233
TI  - Novel function of the poly(c)-binding protein alpha-CP2 as a transcriptional
      activator that binds to single-stranded DNA sequences.
AB  - alpha-complex protein 2 (alpha-CP2) is known as an RNA-binding protein that
      interacts in a sequence-specific manner with single-stranded polycytosine
      [poly(C)]. This protein is involved in various post-transcriptional regulations,
      such as mRNA stabilization and translational regulation. In this study, the full
      length mouse alpha-CP2 gene was expressed in an insoluble form with an N-terminal
      histidine tag in Escherichia coli and purified for homogeneity using affinity
      column chromatography. Its identity was confirmed using matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. Recombinant
      alpha-CP2 was expressed and refolded. The protein folding conditions for
      denatured alpha-CP2 were optimized. DNA and RNA electrophoretic mobility shift
      assays demonstrated that the recombinant alpha-CP2 is capable of binding to both
      single-stranded DNA and RNA poly(C) sequences. Furthermore, plasmids expressing
      alpha-CP2 activated the expression of a luciferase reporter when co-transfected
      with a single-stranded (pGL-SS) construct containing a poly(C) sequence. To our
      knowledge, this study demonstrates for the first time that alpha-CP2 functions as
      a transcriptional activator by binding to a single-stranded poly(C) sequence.

PMID- 24026234
TI  - Role of state mental health leaders in supporting evidence-based practices over
      time.
AB  - State administrative supports of evidence-based practices (EBPs) may critically
      affect sustainability. As part of a larger follow-up to the multistate National
      Implementing Evidence-Based Practices Project, 13 leaders from eight States
      reported on recent statewide policies and resources that influenced the
      maintenance of 49 EBP programs 6 years after implementation. Nearly three
      quarters (71 %) of the programs were currently operational and adhering to State
      fidelity standards. Most of the programs had level or increased funding over the
      last few years, and most received other State support and resources, such as
      training and technical assistance. Steady State funding as well as State
      sponsored training and expertise appear critical to long-term EBP program
      maintenance.

PMID- 24026235
TI  - Barriers and Enablers to Integrating Mental Health into Primary Care: A Policy
      Analysis.
AB  - Integrating care for physical health and behavioural health (mental health and
      addictions) has been a longstanding challenge, although research supports the
      clinical and cost effectiveness of integrated care for many clients. In one such
      model, primary care (PC) physicians work with specialist physicians and non
      physician providers (NPPs) to provide mental health and addictions care in PC
      settings. This Ontario, Canada-focused policy analysis draws on research evidence
      to examine potential barriers and enablers to this model of integrated care,
      focusing on mental health. Funding challenges pertain to incentivizing PC
      physicians to select patients with mental illness, include NPPs on the treatment
      team, and collaborate with specialist providers. Legal/regulatory challenges
      pertain to NPP scopes of practice for prescribing and counselling. Integrated
      care also requires revising the role of the physician and distribution of
      functions among the team. Policy support to integrate addictions treatment in PC
      may face similar challenges but requires further exploration. 

PMID- 24026237
TI  - Effect of storage method and associated holding time on nitrogen and phosphorus
      concentrations in surface water samples.
AB  - Assessments were conducted to determine the effect of sample storage method and
      associated holding time on surface water nutrient concentrations from field
      sites. Six surface water sites and two nutrient spiked, laboratory water samples
      were evaluated for nitrate, nitrite, ammonium, filtered orthophosphorus, and
      total orthophosphorus concentrations on four separate days throughout the period
      of 1 year. Samples stored at ambient temperature (23 degrees C) for 24 h prior to
      nutrient analyses resulted in 18 % +/- 2 % of results being significantly
      different from controls (which were analyzed immediately upon collection).
      Samples placed in the cooler (4 degrees C) for 7 days prior to nutrient analyses
      resulted in 30 % +/- 1 % of values being significantly different from controls.
      Samples placed in the freezer (-20 degrees C) for 7 days prior to analyses
      resulted in 34 % +/- 12 %, 44 % +/- 10 %, and 28 % +/- 5.7 % of ammonium,
      filtered orthophosphate, and total orthophosphate, respectively, values being
      significantly different from controls. This study highlights the challenges
      facing researchers in efficient collection, storage and nutrient analysis of
      samples, especially when sites are remote and difficult to access .

PMID- 24026236
TI  - Assessing the legacy of a legislative Workgroup for bidirectional integration of
      services.
AB  - Across the USA, health care systems are recognizing the value of integrating
      behavioral health services and primary care. The Texas Legislature took a unique
      approach to integration, passing legislation creating a Workgroup to explore key
      issues, identify best practices, and recommend policy and practice changes. This
      article situates the Workgroup in a rapidly evolving policy environment,
      describing the passage of integrated health care legislation in Texas, the
      Integration of Health and Behavioral Health Services Workgroup that was created
      by the legislation, and the policy recommendations that emerged from the
      Workgroup. The article analyzes how the Workgroup process intersected with a
      changing policy environment in Texas and nationally, opening the door for
      essential collaboration and partnership. The Workgroup ultimately laid the
      groundwork for integration's key role in a comprehensive Medicaid transformation
      waiver designed to expand access, improve population health and satisfaction with
      treatment, while better managing costs. 

PMID- 24026238
TI  - Non-toxic amyloid beta formed in the presence of glypican-1 or its deaminatively
      generated heparan sulfate degradation products.
AB  - The amyloid beta (Abeta) peptides (mainly Abeta40 and Abeta42), which are derived
      from the amyloid precursor protein (APP), can oligomerize into antibody A11
      positive, neurotoxic species, believed to be involved in Alzheimer's disease.
      Interestingly, APP binds strongly to the heparan sulfate (HS) proteoglycan (PG)
      glypican-1 (Gpc-1) in vitro and both proteins are colocalized inside cells. In
      endosomes, APP is proteolytically processed to yield Abeta peptides. The HS
      chains of S-nitrosylated (SNO) Gpc-1 PG are cleaved into anhydromannose (anMan)
      containing di- and oligosaccharides by an NO-dependent reaction in the same
      compartments. Here, we have studied the toxicity of oligomers/aggregates of
      Abeta40 and Abeta42, as well as Abeta40/42 mixtures that were formed in the
      presence of immobilized Gpc-1 PG or immobilized HS oligosaccharides. Afterwards,
      Abeta was displaced from the matrices, analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and assayed for A11 immunoreactivity, for
      effects on growth of mouse N2a neuroblastoma cells and for membrane leakage in
      rat cortical neurons. HS generally promoted and accelerated Abeta multimerization
      into oligomers as well as larger aggregates that were mostly A11 positive and
      showed toxic effects. However, non-toxic Abeta was formed in the presence of Gpc
      1 PG or when anMan-containing HS degradation products were simultaneously
      generated. Both toxic and non-toxic Abeta peptides were taken up by the cells but
      toxic forms appeared to enter the nuclei to a larger extent. The protection
      afforded by the presence of HS degradation products may reflect a normal
      intracellular function for the Abeta peptides. 

PMID- 24026240
TI  - Providing guidance in the dark: rare renal diseases and the challenge to improve
      the quality of evidence.
AB  - Among renal diseases, over 100 conditions meet the epidemiological criteria to be
      defined as rare, including disorders in development, transport and metabolism.
      Clinical management of rare diseases is likely to be less investigated than that
      of common disorders and for this reason the scientific evidence to support
      clinical practice is limited. Furthermore, no specific and validated methods for
      designing, carrying out or analyzing clinical trials in small populations exist
      with important consequences for evidence-based medicine. In this paper we aim at
      discussing the inherent difficulty in finding evidence in rare renal diseases,
      providing some suggestions on how the quality of evidence and the guidance in
      these diseases can be improved. 

PMID- 24026239
TI  - Identifying human milk glycans that inhibit norovirus binding using surface
      plasmon resonance.
AB  - Human milk glycans inhibit binding between norovirus and its host glycan
      receptor; such competitive inhibition by human milk glycans is associated with a
      reduced risk of infection. The relationship between the presence of specific
      structural motifs in the human milk glycan and its ability to inhibit binding by
      specific norovirus strains requires facile, accurate and miniaturized-binding
      assays. Toward this end, a high-throughput biosensor platform was developed based
      on surface plasmon resonance imaging (SPRi) of glycan microarrays. The SPRi was
      validated, and its utility was tested, by measuring binding specificities between
      defined human milk glycan epitopes and the capsids of two common norovirus
      strains, VA387 and Norwalk. Human milk oligosaccharide (HMOS)-based
      neoglycoconjugates, including chemically derived neoglycoproteins and
      oligosaccharide-glycine derivatives, were used to represent polyvalent
      glycoconjugates and monovalent oligosaccharides, respectively, in human milk.
      SPRi binding results established that the glycan motifs that bind norovirus
      capsids depend upon strain; VA387 capsid interacts with two neoglycoproteins,
      whereas Norwalk capsid binds to a different set of HMOS motifs in the form of
      both polyvalent neoglycoproteins and monovalent oligosaccharides. SPRi
      competitive binding assays further demonstrated that specific norovirus-binding
      glycans are able to inhibit norovirus capsid binding to their host receptors. A
      polyvalent neoglycoconjugate with clustered carbohydrate moieties is required for
      the inhibition of VA387 capsid binding to host receptor glycans, whereas both
      monovalent oligosaccharides and polyvalent neoglycoconjugates are able to inhibit
      Norwalk capsid binding to its host receptor. Binding of HMOS and HMOS-based
      neoglycoconjugates to norovirus capsids depends upon the specific strain
      characteristics, implying that HMOS and their polyvalent derivatives are
      potential anti-adhesive agents for norovirus prophylaxis. 

PMID- 24026241
TI  - Frequent-relapsing, steroid-dependent minimal change disease: is rituximab the
      answer?

PMID- 24026242
TI  - Balancing thromboembolic risk against vitamin K antagonist-related bleeding and
      accelerated calcification: is fondaparinux the Holy Grail for end-stage renal
      disease patients with atrial fibrillation?

PMID- 24026243
TI  - The nephronophthisis gene product NPHP2/Inversin interacts with Aurora A and
      interferes with HDAC6-mediated cilia disassembly.
AB  - BACKGROUND: Nephronophthisis (NPH) is a rare recessive disease caused by several
      different gene mutations. Most gene products localize to the cilium, and thus,
      the various NPH manifestations including kidney cysts and situs inversus have
      been linked to ciliary defects. RESULTS: Here, we describe that targeted
      knockdown of NPHP2 significantly reduced the number of cilia on polarized MDCK
      cells. As one of the underlying molecular mechanisms, we identified a direct
      interaction between NPHP2 and Aurora A, a cell cycle kinase that promotes ciliary
      disassembly after activation by Hef1. NPHP2 inhibited the phosphorylation and
      activation of Aurora A, and reduced its kinase activity in vitro. Aurora A and
      histone deacetylase inhibitors ameliorated the ciliogenesis defect in NPHP2
      deficient MDCK cells, supporting our hypothesis that NPHP2 is involved in the
      control of ciliary disassembly. Furthermore, we observed that nephrocystin
      (NPHP1), an interaction partner of NPHP2, also binds Aurora A, exerting very
      similar inhibitory effects on Hef1-mediated Aurora A activation. CONCLUSIONS:
      Taken together, these findings suggest that NPHP gene products can interfere with
      ciliary disassembly through interaction with the Hef1/Aurora A module, thereby
      modulating cell cycle control and cell proliferation.

PMID- 24026244
TI  - Canonical and non-canonical effects of the NLRP3 inflammasome in kidney
      inflammation and fibrosis.
AB  - NLRP-3 inflammasome is one of several intracellular danger recognition platforms
      that integrates infectious or non-infectious types of danger into the expression
      of pro-inflammatory cytokines to set-up inflammation for danger control. NLRP3
      activation induces three types of caspase-1-mediated responses: secretion of IL
      1beta, secretion of IL-18 and a programmed form of cell death, referred to as
      pyroptosis. Similar to the well-documented impact of Toll-like receptor-driven
      danger signalling in kidney disease, evolving data now suggest a similar
      involvement of the NLRP3 inflammasome in renal inflammation. Here, we discuss the
      accumulating data on NLRP3 in the kidney: its IL-1beta and IL-18-dependent
      'canonical' effects and the current evidence for its 'non-canonical' effects,
      e.g. in tumor growth factor (TGF)-beta signalling, epithelial-mesenchymal
      transition and fibrosis. Research in this area will certainly uncover yet unknown
      aspects of danger signalling in the kidney and how it drives renal inflammation
      and immunopathology. 

PMID- 24026246
TI  - Overweight/obesity revisited as a predictive risk factor in primary IgA
      nephropathy.
AB  - BACKGROUND: The absolute renal risk (ARR) of dialysis/death in IgA nephropathy
      (IgAN) was based on three major, independent equipotent risk factors:
      hypertension, proteinuria >=1 g/day and severe pathological score at diagnosis.
      We studied, in our prospective regional cohort of IgAN, the impact of body mass
      index (BMI) on the ultimate outcome in light of this ARR concept. METHODS: We had
      information on 331 IgAN patients (233 men). At diagnosis, the BMI was normal (<25
      kg/m(2)) in 195 and elevated (>=25) in 136 (44.1%) with 102 overweight (25-29.9)
      and 34 obese (>=35) defining two groups, normal BMI and elevated BMI,
      subsequently compared. RESULTS: At diagnosis, in the overweight/obese group,
      hypertension and proteinuria >=1 g/day were more frequent (respectively, P <
      0.0001 and P = 0.0006) and the mean global optical score was increased (P =
      0.002). This resulted in a worse ARR scoring distribution (P < 0.0001). In
      addition, these patients with an elevated BMI were ~10 years older (P < 0.0001),
      including more obese women and with an eGFR already lower (P = 0.0003). At last
      follow-up, in the overweight/obese group, progression remained worse with greater
      prevalence of CKD-3+ (43.4 versus 21.0%; P < 0.0001) and dialysis/death events
      (21.3 versus 13.9%). Kaplan-Meier survival and Cox regression analyses
      demonstrated that ARR remained a powerful independent risk factor for prediction
      of events, but not BMI. CONCLUSIONS: IgAN patients with an elevated BMI at
      diagnosis had a significantly worse presentation and worse final outcome.
      Overweight/obesity increased hypertension frequency, proteinuria level and some
      renal lesions all of which translate into a worse ARR for prediction of CKD-3+ or
      dialysis alone or dialysis/death, with no apparent direct effect of BMI per se.

PMID- 24026245
TI  - Modification of Diet in Renal Disease versus Chronic Kidney Disease Epidemiology
      Collaboration equation to estimate glomerular filtration rate in obese patients.
AB  - BACKGROUND: Obesity is a recognized risk factor for both the development and
      progression of chronic kidney disease (CKD). Accurate estimation of glomerular
      filtration rate (GFR) is thus important in these patients. We tested the
      performances of two creatinine-based GFR estimates, the Modification of Diet in
      Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration
      (CKD-EPI) equations, in an obese population. METHODS: Patients with body mass
      index (BMI) > 30 kg/m(2) were included. The reference method for measured GFR
      (mGFR) was (51)Cr-EDTA (single-injection method, two blood samples at 120 and 240
      min). Both indexed and non-indexed results were considered. Serum creatinine was
      measured using the IDMS-traceable compensated Jaffe method. Mean bias (eGFR
      mGFR), precision (SD around the bias) and accuracy within 30% (percentage of
      estimations within 30% of mGFR) were calculated for both equations. RESULTS: The
      population included 366 patients (185 women) from two different areas. Mean age
      was 55 +/- 14 years, and mean BMI was 36 +/- 7 kg/m(2). Mean mGFR was 56 +/- 26
      mL/min/1.73 m(2) (71 +/- 35 mL/min without indexation). In the total population,
      mean bias was +1.9 +/- 14.3 and +4.6 +/- 14.7 mL/min/1.73 m(2) (P < 0.05), and
      accuracy 30% was 80 and 76% for the MDRD and CKD-EPI equations (P < 0.05),
      respectively. In patients with mGFR > 60 mL/min/1.73 m(2), mean bias was +4.6 +/-
      18.4 and +9.3 +/- 17.2 mL/min/1.73 m(2) (P < 0.05), and accuracy 30% was 81 and
      79% (NS) for the MDRD and CKD-EPI equations, respectively. CONCLUSIONS: The CKD
      EPI equation did not outperform the MDRD study equation in this population of
      obese patients.

PMID- 24026247
TI  - Inflammatory profile in cerebrospinal fluid of patients with headache as a
      manifestation of neuropsychiatric systemic lupus erythematosus.
AB  - OBJECTIVE: The objective of this study was to define the cytokine and chemokine
      profiles in cerebrospinal fluid (CSF) from patients with headache as
      neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: In a post hoc
      analysis, seven patients hospitalized because of headache were included. Patients
      were evaluated at hospitalization and 6 months later and a CSF sample was
      obtained. As controls, CSF from 27 patients with other NPSLE syndromes, 16 SLE
      patients without a history of NP manifestations (non-NPSLE) and 25 patients with
      non-autoimmune diseases were studied. Soluble molecules including cytokines (IL
      2, IL-4, IL-6, IL-10, TNF-alpha, IFN-alpha and IFN-gamma) and chemokines
      [monocyte chemotactic protein-1, RANTES (regulated on activation normal T cell
      expressed and secreted), IL-8, monokine induced by IFN-gamma (MIG), and IFN-gamma
      induced protein 10 (IP-10)] were measured with the use of cytometric bead array
      kits or luminometry. RESULTS: Patients with headache had increased CSF values in
      the following molecules compared with non-NPSLE and non-autoimmune diseases
      patients, respectively: IL-6 (208.5, 3.0, 3.0 pg/ml, P < 0.004 and P < 0.001), IL
      8 (406.6, 30.0, 19.7 pg/ml, P < 0.05 and P < 0.004), IP-10 (4673, 329.7, 113.6
      pg/ml, P = 0.02 and P < 0.002), RANTES (7.5, 2.5, 2.2 pg/ml, P < 0.003 for both)
      and MIG (944.7, 11.4, 3.5 pg/ml, P = 0.02 and P = 0.001). No clear difference was
      observed between patients with headache and other NPSLE. Higher levels of
      inflammatory molecules were found in patients with headache from intracranial
      hypertension and intractable non-specific headache than patients with migraine.
      Six months later, when the headache had resolved, all the elevated molecule
      levels had decreased significantly. CONCLUSION: Headache from intracranial
      hypertension and intractable non-specific headache, but not migraine, share the
      inflammatory profile in CSF observed in other NPSLE syndromes.

PMID- 24026248
TI  - The emerging role of epigenetics in rheumatic diseases.
AB  - Epigenetics is a key mechanism regulating the expression of genes. There are
      three main and interrelated mechanisms: DNA methylation, post-translational
      modification of histone proteins and non-coding RNA. Gene activation is generally
      associated with lower levels of DNA methylation in promoters and with distinct
      histone marks such as acetylation of amino acids in histones. Unlike the genetic
      code, the epigenome is altered by endogenous (e.g. hormonal) and environmental
      (e.g. diet, exercise) factors and changes with age. Recent evidence implicates
      epigenetic mechanisms in the pathogenesis of common rheumatic disease, including
      RA, OA, SLE and scleroderma. Epigenetic drift has been implicated in age-related
      changes in the immune system that result in the development of a pro-inflammatory
      status termed inflammageing, potentially increasing the risk of age-related
      conditions such as polymyalgia rheumatica. Therapeutic targeting of the epigenome
      has shown promise in animal models of rheumatic diseases. Rapid advances in
      computational biology and DNA sequencing technology will lead to a more
      comprehensive understanding of the roles of epigenetics in the pathogenesis of
      common rheumatic diseases. 

PMID- 24026249
TI  - Anti-SSA Ro52/Ro60 antibody testing by immunodot could help the diagnosis of
      Sjogren's syndrome in the absence of anti-SSA/SSB antibodies by ELISA.
AB  - OBJECTIVE: The objective of this study was to assess the diagnostic value of anti
      Ro52/60 antibodies by immunodot in patients with suspected SS. METHODS: All
      patients between 2008 and 2012 with suspected SS without anti-SSA/SSB antibodies
      by ELISA and who had a determination of anti-SSA (Ro52/Ro60) antibodies by
      immunodot (Euroimmun, Germany) were retrospectively analysed. RESULTS: Eighty
      four patients (median age 62 years; males 35 cases) were included. Forty-five
      patients had associated interstitial lung disease (ILD). American-European
      Consensus Group (AECG) criteria for SS were fulfilled in 10 patients (12%) with a
      positive salivary gland biopsy, and among them 2 patients had anti-Ro52
      antibodies by dot (20%). Among 74 patients with a negative salivary gland biopsy,
      16 (22%) had anti-Ro52/60 antibodies and 10 (14%) fulfilled AECG criteria when
      including Ro52/60 antibodies. A comparison of patients with and without anti
      Ro52/60 antibodies revealed no differences, except gamma globulin levels and more
      frequent steroid use in patients with anti-Ro52/60 antibodies (P < 0.05). In 45
      patients with ILD and dry eye/mouth syndrome, 10 (22%) had positive anti-Ro52/60
      antibodies. In these patients 2 (4%) fulfilled AECG criteria without anti-Ro52/60
      antibodies vs 4 (8%) patients if anti-Ro52/60 antibodies were included.
      CONCLUSION: In patients with dry eye/mouth syndrome without anti-SSA/SSB
      antibodies by ELISA, the detection of anti-Ro52/Ro60 antibodies by dot could help
      in the diagnosis of SS. In patients with ILD, the lower frequency of a Chisholm
      score >=3 enhances the interest of anti-Ro52/Ro60 screening.

PMID- 24026250
TI  - Unilateral vs bilateral symptomatic knee osteoarthritis: associations between
      pain intensity and function.
AB  - OBJECTIVE: The objective of this study was to determine if associations between
      pain distribution (unilateral vs bilateral) and measures of function (self-report
      vs performance-based) were influenced by knee pain intensity of the painful
      knee(s) in persons with moderate to severe symptomatic knee OA. METHODS: Data
      from persons in the Osteoarthritis Initiative (OAI) dataset (n = 852) with
      symptomatic knee OA were studied. Key dependent variables were the WOMAC physical
      function, Knee Injury and Osteoarthritis Outcome Score (KOOS) quality of life,
      the repeated chair stand test and the 20-m walk test. In addition to covariates,
      the independent variables were the presence of unilateral or bilateral OA
      involvement (either Kellgren and Lawrence grade 3 or 4 or a grade <3) and pain
      category (mild, moderate or severe). RESULTS: WOMAC physical function scores
      consistently showed the strongest association with pain intensity for persons
      with unilateral vs bilateral knee pain. For example, in persons with unilateral
      severe knee pain, WOMAC scores averaged 19.9 (S.D. = 12.0) points while persons
      with bilateral knee pain with at least one knee rated as severe had WOMAC scores
      ranging from 25.3 to 28.9, depending on pain severity of the contralateral knee.
      These differences were statistically significant (P < 0.001) as was the test for
      trend (P = 0.001). Self-report measures generally showed larger effect sizes than
      performance-based measures. CONCLUSION: Knee pain intensity influences self
      report and performance-based tests differently depending on whether knee pain is
      unilateral or bilateral. WOMAC scores are most strongly associated with pain
      intensity in persons with unilateral vs bilateral pain while walking tests are
      least influenced by pain intensity.

PMID- 24026251
TI  - Ethanol induces cell cycle arrest and triggers apoptosis via Sp1-dependent p75NTR
      expression in human neuroblastoma cells.
AB  - Ethanol exposure has deleterious effects on the central nervous system. Although
      several mechanisms for ethanol-induced damage have been suggested, the precise
      mechanism underlying ethanol-induced neuronal cell death remains unclear. Recent
      studies indicate that the p75 neurotrophin receptor (p75NTR) has a critical role
      in the regulation of neuronal survival. This study was designed to examine the
      role of p75NTR in ethanol-induced apoptotic signaling in neuroblastoma cells.
      Ethanol caused highly increased level of p75NTR expression. The use of small
      interfering RNA to inhibit p75NTR expression markedly attenuated ethanol-induced
      cell cycle arrest and apoptosis. DNA binding activity of Sp1 was increased by
      ethanol, whereas inhibition of Sp1 activity by mithramycin, a Sp1 inhibitor, or
      short hairpin RNA suppressed ethanol-induced p75NTR expression. In addition,
      inhibitors of casein kinase 2 (CK2) and extracellular signal-regulated kinase
      (ERK) augmented ethanol-induced p75NTR expression. Our results also demonstrate
      that inhibition of ERK and CK2 caused a further increase in the activation of the
      p75NTR proximal promoter induced by ethanol. This increased activation was
      partially suppressed by the deletion of the Sp1 binding sites. These results
      suggest that Sp1-mediated p75NTR expression is regulated at least in part by ERK
      and CK2 pathways. The present study also showed that treatment with ethanol
      resulted in significant increases in the expression of p21, but not the levels of
      p53 and p53 target genes such as Bax, Puma, and Bcl-2. Furthermore, the
      inhibition of p75NTR expression or Sp1 activity suppressed ethanol-induced p21
      expression, cell cycle arrest, and apoptosis. These data suggest that ethanol
      increases p75NTR expression, and CK2 and ERK signaling inversely regulate Sp1
      mediated p75NTR expression in ethanol-treated neuroblastoma cells. Thus, our
      study provides more insight into the mechanisms underlying ethanol actions. 

PMID- 24026252
TI  - An integrated population pharmacokinetic meta-analysis of propofol in morbidly
      obese and nonobese adults, adolescents, and children.
AB  - This study describes a population pharmacokinetic meta-analysis of propofol to
      characterize the influence of body size measures and age in morbidly obese and
      nonobese adults, adolescents, and children. Sixty morbidly obese and nonobese
      adult patients (55-167 kg; 21-79 years) and 34 morbidly obese and nonobese
      adolescents and children (37-184 kg; 9-20 years) were included. The results show
      that clearance increased with total body weight in an allometric function while
      age was found to influence clearance in a bilinear fashion with two distinct
      slopes, reflecting an initial increase and subsequent decrease as a result of
      aging. Using these two functions, the influence of both (over)weight and age on
      propofol clearance was well characterized, which may provide a basis for dosing
      across this diverse group of patients.CPT: Pharmacometrics & Systems Pharmacology
      (2013) 2, e73; doi:10.1038/psp.2013.47; advance online publication 11 September
      2013. 

PMID- 24026253
TI  - Systems pharmacology models can be used to understand complex pharmacokinetic
      pharmacodynamic behavior: an example using 5-lipoxygenase inhibitors.
AB  - Zileuton, a 5-lipoxygenase (5LO) inhibitor, displays complex pharmaokinetic (PK)
      pharmacodynamic (PD) behavior. Available clinical data indicate a lack of dose
      bronchodilatory response during initial treatment, with a dose response
      developing after ~1-2 weeks. We developed a quantitative systems pharmacology
      (QSP) model to understand the mechanism behind this phenomenon. The model
      described the release, maturation, and trafficking of eosinophils into the
      airways, leukotriene synthesis by the 5LO enzyme, leukotriene signaling and
      bronchodilation, and the PK of zileuton. The model provided a plausible
      explanation for the two-phase bronchodilatory effect of zileuton-the short-term
      bronchodilation was due to leukotriene inhibition and the long-term
      bronchodilation was due to inflammatory cell infiltration blockade. The model
      also indicated that the theoretical maximum bronchodilation of both 5LO
      inhibition and leukotriene receptor blockade is likely similar. QSP modeling
      provided interesting insights into the effects of leukotriene modulation.CPT:
      Pharmacometrics & Systems Pharmacology (2013) 2, e74; doi:10.1038/psp.2013.49;
      advance online publication 11 September 2013. 

PMID- 24026254
TI  - Genomic counseling: next generation counseling.
AB  - Personalized medicine continues to expand with the development and increasing use
      of genome-based testing. While these advances present new opportunities for
      diagnosis and risk assessment, they also present challenges to clinical delivery.
      Genetic counselors will play an important role in ushering in this new era of
      testing; however, it will warrant a shift from traditional genetic counseling to
      "genomic counseling." This shift will be marked by a move from reactive genetic
      testing for diagnosis of primarily single-gene diseases to proactive genome-based
      testing for multiple complex diseases for the purpose of disease prevention. It
      will also require discussion of risk information for a number of diseases, some
      of which may have low relative risks or weak associations, and thus, may not
      substantially impact clinical care. Additionally, genomic counselors will expand
      their roles, particularly in the area of health promotion to reduce disease risk.
      This additional role will require a style of counseling that is more directive
      than traditional counseling and require greater knowledge about risk reducing
      behaviors and disease screening. 

PMID- 24026255
TI  - Living with wildlife and mitigating conflicts around three Indian protected
      areas.
AB  - Crop and livestock losses to wildlife are a concern for people neighboring many
      protected areas (PAs) and can generate opposition to conservation. Examining
      patterns of conflict and associated tolerance is important to devise policies to
      reduce conflict impacts on people and wildlife. We surveyed 398 households from
      178 villages within 10 km of Ranthambore, Kanha, and Nagarahole parks in India.
      We compared different attitudes toward wildlife, and presented hypothetical
      response scenarios, including killing the problem animal(s). Eighty percent of
      households reported crop losses to wildlife and 13 % livestock losses. Higher
      crop loss was associated with more cropping months per year, greater crop
      variety, and more harvest seasons per year but did not vary with proximity to the
      PA, suggesting that PAs are not necessarily "sources" for crop raiders. By
      contrast, complaints of "depredating carnivores" were associated with people
      grazing animals and collecting resources from PAs. Many households (83 %) engaged
      in mitigation efforts. We found that only fencing and guard animals reduce crop
      losses, and no efforts to lower livestock losses. Contrary to our expectations,
      carnivores were not viewed with more hostility than crop-raiding wildlife.
      Households reported greater inclination to kill herbivores destroying crops or
      carnivores harming people, but not carnivores preying on livestock.Our model
      estimated probability of [corrected] crop loss was 82 % across surveyed
      households (highest in Kanha),while the livestock loss experienced was 27 %
      (highest in Ranthambore). Our comparative study provides insights into factors
      associated with conflict loss and tolerance, and aids in improving ongoing
      conservation and compensation efforts.

PMID- 24026256
TI  - Blood pressure and mortality in U.S. veterans with chronic kidney disease: a
      cohort study.
AB  - BACKGROUND: The ideal blood pressure (BP) to decrease mortality rates in patients
      with non-dialysis-dependent chronic kidney disease (CKD) is unclear. OBJECTIVE:
      To assess the association of BP (defined as the combination of systolic BP [SBP]
      and diastolic BP [DBP] at the individual level) with death in patients with CKD.
      DESIGN: Historical cohort between 2005 and 2012. SETTING: All U.S. Department of
      Veterans Affairs health care facilities. PATIENTS: 651 749 U.S. veterans with
      CKD. MEASUREMENTS: All possible combinations of SBP and DBP were examined in 96
      categories from lowest (<80/<40 mm Hg) to highest (>210/>120 mm Hg), in 10-mm Hg
      increments. Associations with all-cause mortality were examined in time-dependent
      Cox models with adjustment for relevant confounders. RESULTS: Patients with SBP
      of 130 to 159 mm Hg combined with DBP of 70 to 89 mm Hg had the lowest adjusted
      mortality rates, and those in whom both SBP and DBP were concomitantly very high
      or very low had the highest mortality rates. Patients with moderately elevated
      SBP combined with DBP no less than 70 mm Hg had consistently lower mortality
      rates than did patients with ideal SBP combined with DBP less than 70 mm Hg.
      Results were consistent in subgroups of patients with normal and elevated urinary
      microalbumin-creatinine ratios. LIMITATION: Mostly male patients, inability to
      establish causality, and large number of patients missing proteinuria
      measurement. CONCLUSION: The optimal BP in patients with CKD seems to be 130 to
      159/70 to 89 mm Hg. It may not be advantageous to achieve ideal SBP at the
      expense of lower-than-ideal DBP in adults with CKD. PRIMARY FUNDING SOURCE:
      National Institute of Diabetes and Digestive and Kidney Diseases, National
      Institutes of Health, and U.S. Department of Veterans Affairs.

PMID- 24026257
TI  - A home-based intervention to reduce depressive symptoms and improve quality of
      life in older African Americans: a randomized trial.
AB  - BACKGROUND: Effective care models for treating older African Americans with
      depressive symptoms are needed. OBJECTIVE: To determine whether a home-based
      intervention alleviates depressive symptoms and improves quality of life in older
      African Americans. DESIGN: Parallel, randomized trial stratified by recruitment
      site. Interviewers assessing outcomes were blinded to treatment assignment.
      (ClinicalTrials.gov: NCT00511680). SETTING: A senior center and participants'
      homes from 2008 to 2010. PATIENTS: African Americans aged 55 years or older with
      depressive symptoms. INTERVENTION: A multicomponent, home-based intervention
      delivered by social workers or a wait-list control group that received the
      intervention at 4 months. MEASUREMENTS: Self-reported depression severity at 4
      months (primary outcome) and depression knowledge, quality of life, behavioral
      activation, anxiety, function, and remission at 4 and 8 months. RESULTS: Of 208
      participants (106 and 102 in the intervention and wait-list groups,
      respectively), 182 (89 and 93, respectively) completed 4 months and 160 (79 and
      81, respectively) completed 8 months. At 4 months, participants in the
      intervention group showed reduced depression severity (difference in mean change
      in Patient Health Questionnaire-9 score from baseline, -2.9 [95% CI, -4.6 to 
      1.2]; difference in mean change in Center for Epidemiologic Studies Depression
      Scale score from baseline, -3.7 [CI, -5.4 to -2.1]); improved depression
      knowledge, quality of life, behavioral activation, and anxiety (P < 0.001); and
      improved function (P = 0.014) compared with wait-list participants. More
      intervention than wait-list participants entered remission at 4 months (43.8% vs.
      26.9%). After treatment, control participants showed benefits similar in
      magnitude to those of participants in the initial intervention group. Those in
      the initial intervention group maintained benefits at 8 months. LIMITATION: The
      study had a small sample, short duration, and differential withdrawal rate.
      CONCLUSION: A home-based intervention delivered by social workers could reduce
      depressive symptoms and enhance quality of life in most older African Americans.
      PRIMARY FUNDING SOURCE: National Institute of Mental Health.

PMID- 24026258
TI  - Tofacitinib in combination with nonbiologic disease-modifying antirheumatic drugs
      in patients with active rheumatoid arthritis: a randomized trial.
AB  - BACKGROUND: Many patients with rheumatoid arthritis (RA) do not achieve adequate
      and safe responses with disease-modifying antirheumatic drugs (DMARDs).
      Tofacitinib is a novel, oral, Janus kinase inhibitor that treats RA. OBJECTIVE:
      To evaluate the efficacy and safety of tofacitinib in combination with
      nonbiologic DMARDs. DESIGN: 1-year, double-blind, randomized trial
      (ClinicalTrials.gov: NCT00856544). SETTING: 114 centers in 19 countries.
      PATIENTS: 792 patients with active RA despite nonbiologic DMARD therapy.
      INTERVENTION: Patients were randomly assigned 4:4:1:1 to oral tofacitinib, 5 mg
      or 10 mg twice daily, or placebo advanced to tofacitinib, 5 mg or 10 mg twice
      daily. MEASUREMENTS: Primary end points were 20% improvement in American College
      of Rheumatology (ACR20) criteria; Disease Activity Score for 28-joint counts
      based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6;
      DAS28-4(ESR)-defined remission, change in Health Assessment Questionnaire
      Disability Index (HAQ-DI) score, and safety assessments. RESULTS: Mean treatment
      differences for ACR20 response rates (month 6) for the 5-mg and 10-mg tofacitinib
      groups compared with the combined placebo groups were 21.2% (95% CI, 12.2% to
      30.3%; P < 0.001) and 25.8% (CI, 16.8% to 34.8%; P < 0.001), respectively. The
      HAQ-DI scores (month 3) and DAS28-4(ESR) less than 2.6 response rates (month 6)
      were also superior in the tofacitinib groups versus placebo. The incidence rates
      of serious adverse events for patients receiving 5-mg tofacitinib, 10-mg
      tofacitinib, or placebo were 6.9, 7.3, or 10.9 events per 100 patient-years of
      exposure, respectively. In the tofacitinib groups, 2 cases of tuberculosis, 2
      cases of other opportunistic infections, 3 cardiovascular events, and 4 deaths
      occurred. Neutrophil counts decreased, hemoglobin and low- and high-density
      lipoprotein cholesterol levels increased, and serum creatinine levels had small
      increases in the tofacitinib groups. LIMITATIONS: Placebo groups were smaller and
      of shorter duration. Patients received primarily methotrexate. The ability to
      assess drug combinations other than tofacitinib plus methotrexate was limited.
      CONCLUSION: Tofacitinib improved disease control in patients with active RA
      despite treatment with nonbiologic DMARDs, primarily methotrexate. PRIMARY
      FUNDING SOURCE: Pfizer.

PMID- 24026259
TI  - Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: a systematic
      review and meta-analysis.
AB  - BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of
      antidiabetic drugs. PURPOSE: To assess the efficacy and safety of SGLT2
      inhibitors in adults with type 2 diabetes. DATA SOURCES: MEDLINE, EMBASE, and the
      Cochrane Library from inception through April 2013 without language restrictions;
      regulatory authorities' reports; and gray literature. STUDY SELECTION: Randomized
      trials comparing SGLT2 inhibitors with placebo or other medication for type 2
      diabetes. DATA EXTRACTION: Three reviewers extracted or checked data for study
      characteristics, outcomes of interest, and risk of bias, and 3 reviewers
      summarized strength of evidence using the Grading of Recommendations Assessment,
      Development and Evaluation approach. DATA SYNTHESIS: Sodium-glucose cotransporter
      2 inhibitors were compared with placebo in 45 studies (n = 11 232) and with
      active comparators in 13 studies (n = 5175). They had a favorable effect on
      hemoglobin A1c level (mean difference vs. placebo, -0.66% [95% CI, -0.73% to 
      0.58%]; mean difference vs. active comparators, -0.06% [CI, -0.18% to 0.05%]).
      Sensitivity analyses incorporating unpublished data showed similar effect
      estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean
      difference, -1.80 kg [CI, -3.50 to -0.11 kg]) and systolic blood pressure (mean
      difference, -4.45 mm Hg [CI, -5.73 to -3.18 mm Hg]). Urinary and genital tract
      infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to
      1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar
      to that of other agents. Results for cardiovascular outcomes and death were
      inconclusive. An imbalance in incidence of bladder and breast cancer was noted
      with dapagliflozin compared with control. LIMITATION: Most trials were rated as
      high risk of bias because of missing data and last-observation-carried-forward
      methods. CONCLUSION: Sodium-glucose cotransporter 2 inhibitors may improve short
      term outcomes in adults with type 2 diabetes, but effects on long-term outcomes
      and safety are unclear. PRIMARY FUNDING SOURCE: None.

PMID- 24026260
TI  - Comparative effectiveness of new oral anticoagulants and standard
      thromboprophylaxis in patients having total hip or knee replacement: a systematic
      review.
AB  - BACKGROUND: Pharmacologic thromboprophylaxis reduces the risk for venous
      thromboembolism after total hip replacement (THR) or total knee replacement
      (TKR). New oral anticoagulants (NOACs), including direct thrombin inhibitors and
      factor Xa inhibitors, are emerging options for thromboprophylaxis after these
      procedures. PURPOSE: To compare the benefits and risks of NOACs versus standard
      thromboprophylaxis for adults having THR or TKR. DATA SOURCES: MEDLINE, EMBASE,
      and the Cochrane Database of Systematic Reviews from January 2009 through March
      2013. STUDY SELECTION: English-language systematic reviews. DATA EXTRACTION: Two
      independent reviewers abstracted data and rated study quality and strength of
      evidence. DATA SYNTHESIS: Six good-quality systematic reviews compared NOACs with
      low-molecular-weight heparin (LMWH) for thromboprophylaxis after THR or TKR. Risk
      for symptomatic deep venous thrombosis, but not risk for death or nonfatal
      pulmonary embolism, was reduced with factor Xa inhibitors compared with LMWH (4
      fewer events per 1000 patients). Conversely, the risk for major bleeding
      increased (2 more events per 1000 patients). Outcomes of dabigatran did not
      significantly differ from those of LMWH. Indirect evaluation of NOACs by common
      comparison with LMWH showed nonsignificantly reduced risks for venous
      thromboembolism with rivaroxaban compared with dabigatran (risk ratio [RR], 0.68
      [95% CI, 0.21 to 2.23]) and apixaban (RR, 0.59 [CI, 0.26 to 1.33]) but increased
      major bleeding. New oral anticoagulants have not been compared with warfarin,
      aspirin, or unfractionated heparin. LIMITATIONS: Head-to-head comparisons among
      NOACs were not available. Efficacy is uncertain in routine clinical practice.
      CONCLUSION: New oral anticoagulants are effective for thromboprophylaxis after
      THR and TKR. Their clinical benefits over LMWH are marginal and offset by
      increased risk for major bleeding. PRIMARY FUNDING SOURCE: U.S. Department of
      Veterans Affairs.

PMID- 24026261
TI  - Handling of rescue and missing data affects synthesis and interpretation of
      evidence: the sodium-glucose cotransporter 2 inhibitor example.
AB  - Confidence in evidence summarized in meta-analyses depends on the strength of the
      underlying studies. This inherent limitation of syntheses appears in the case of
      a meta-analysis of sodium-glucose cotransporter 2 inhibitors for the treatment of
      type 2 diabetes because many of the pertinent randomized trials did not handle
      patient dropout and "rescue" medication properly. Repudiated statistical methods,
      such as last observation carried forward, and unsophisticated methods for
      handling postrescue data produce unreliable summary estimates. Future reports of
      randomized studies and meta-analyses of those studies must focus on posing
      precise questions about the treatment effect of interest and then implement
      appropriate statistical methods to account for missing data, patient dropout, and
      use of rescue medication. 

PMID- 24026262
TI  - How low can you go? Blood pressure and mortality in chronic kidney disease.

PMID- 24026263
TI  - Black and white.

PMID- 24026264
TI  - A public health approach to gun violence.

PMID- 24026265
TI  - A public health approach to gun violence.

PMID- 24026266
TI  - A public health approach to gun violence--in response.

PMID- 24026267
TI  - Screening for and treatment of suicide risk relevant to primary care.

PMID- 24026268
TI  - Screening for and treatment of suicide risk relevant to primary care--in
      response.

PMID- 24026271
TI  - Summaries for patients: can a home-based intervention reduce depression in older
      African Americans?

PMID- 24026272
TI  - Summaries for patients: tofacitinib for the treatment of rheumatoid arthritis.

PMID- 24026273
TI  - Summaries for patients: primary care interventions to prevent child maltreatment:
      U.S. Preventive Services Task Force recommendation statement.

PMID- 24026274
TI  - ACP Journal Club. A 12-month, in-home exercise program delayed functional
      deterioration in Alzheimer disease.

PMID- 24026275
TI  - ACP Journal Club. Review: cytisine increases smoking abstinence.

PMID- 24026276
TI  - ACP Journal Club. In patients with sciatica, MRI at 1 year did not differentiate
      between a favorable or unfavorable outcome.

PMID- 24026277
TI  - Valproate use during pregnancy was linked to autism spectrum disorder and
      childhood autism in offspring.

PMID- 24026278
TI  - ACP Journal Club. Review: diagnostic testing does not reassure patients with low
      probability of serious disease.

PMID- 24026279
TI  - ACP Journal Club. Intermittent pneumatic compression reduced deep venous
      thrombosis after stroke.

PMID- 24026280
TI  - ACP Journal Club. Patent foramen ovale closure and medical therapy did not differ
      for recurrence after cryptogenic stroke.

PMID- 24026281
TI  - ACP Journal Club. Patent foramen ovale closure and medical therapy did not differ
      for recurrence after cryptogenic embolism.

PMID- 24026282
TI  - ACP Journal Club. Review: treatment options for asymptomatic carotid artery
      stenosis were compared.

PMID- 24026283
TI  - ACP Journal Club. Warfarin continuation was better than heparin bridging during
      pacemaker or ICD surgery.

PMID- 24026284
TI  - ACP Journal Club. Review: psychosocial and psychological interventions reduce
      postpartum depression.

PMID- 24026285
TI  - ACP Journal Club. Review: in patients with chronic diabetic foot ulcers,
      hyperbaric oxygen reduces major amputations.

PMID- 24026288
TI  - Not eating our young.

PMID- 24026286
TI  - The impact of alpha-toxin on host cell plasma membrane permeability and cytokine
      expression during human blood infection by CA-MRSA USA300.
AB  - This investigation examines the influence of alpha-toxin (Hla) expression by CA
      MRSA on host immune cell integrity and cytokine expression during infection of
      human blood. Flow cytometry analysis of human blood infected by Staphylococcus
      aureus PFGE type USA300 or a USA300Deltahla demonstrated that Hla expression
      significantly increased plasma membrane permeability of human CD14(+) monocytes.
      The increased susceptibility of human CD14(+) monocytes to Hla toxicity
      paralleled the high cell-surface expression on these cell types of ADAM10. USA300
      rapidly associated with PMNs and monocytes but not T cells following inoculation
      of human blood. Transcription analysis indicated a strong up-regulation of
      proinflammatory cytokine transcription following infection of human blood by
      USA300 and USA300Deltahla. CBAs and ELISAs determined that IL-6, IL-10, TNF
      alpha, IFN-gamma, IL-1beta, IL-8, and IL-4 are significantly up-regulated during
      the initial phases of human blood infection by USA300 relative to mock-infected
      blood but failed to distinguish any significant differences in secreted cytokine
      protein concentrations during infection by USA300Deltahla relative to USA300.
      Collectively, these findings demonstrate that expression of Hla by USA300 has a
      significant impact on human CD14(+) monocyte plasma membrane integrity but is not
      exclusively responsible for the proinflammatory cytokine profile induced by
      USA300 during the initial stages of human blood infection. 

PMID- 24026289
TI  - Digital arthrodesis with a one-piece memory nitinol intramedullary fixation
      device: a retrospective review.
AB  - A 1-piece memory Nitinol intramedullary fixation device (Smart Toe; Stryker
      Corporation, Kalamazoo, MI) was used for proximal interphalangeal joint
      arthrodesis for correction of painful hammertoes in digits 2, 3, and 4. Sixty
      five implants were placed in 35 patients. The mean age of our patients was 62.2
      years (range = 27-82; standard deviation = 12.5). Mean follow-up time was 27
      months (range = 12-40 months; standard deviation = 7). Overall, a 93.8% fusion
      rate was noted. Complications were noted in 4 patients (6.1%): 1 asymptomatic
      nonunion (1.5%), 2 hardware failures (3%), and 1 implant displacement (1.5%). To
      date, no patients required revisional surgery or hardware removal. LEVEL OF
      EVIDENCE: V.

PMID- 24026287
TI  - Morphology, input-output relations and synaptic connectivity of Cajal-Retzius
      cells in layer 1 of the developing neocortex of CXCR4-EGFP mice.
AB  - Layer 1 (L1) neurons, in particular Cajal-Retzius (CR) cells are among the
      earliest generated neurons in the neocortex. However, their role and that of L1
      GABAergic interneurons in the establishment of an early cortical microcircuit are
      still poorly understood. Thus, the morphology of whole-cell recorded and biocytin
      filled CR cells was investigated in postnatal day (P) 7-11 old CXCR4-EGFP mice
      where CR cells can be easily identified by their fluorescent appearance. Confocal
      , light- and subsequent electron microscopy was performed to investigate their
      developmental regulation, morphology, synaptic input-output relationships and
      electrophysiological properties. CR cells reached their peak in occurrence
      between P4 to P7 and from thereon declined to almost complete disappearance at
      P14 by undergoing selective cell death through apoptosis. CR cells formed a dense
      and long-range horizontal network in layer 1 with a remarkable high density of
      synaptic boutons along their axons. They received dense GABAergic and non
      GABAergic synaptic input and in turn provided synaptic output preferentially with
      spines or shafts of terminal tuft dendrites of pyramidal neurons. Interestingly,
      no dye-coupling between CR cells with other cortical neurons was observed as
      reported for other species, however, biocytin-labeling of individual CR cells
      leads to co-staining of L1 end foot astrocytes. Electrophysiologically, CR cells
      are characterized by a high input resistance and a characteristic firing pattern.
      Increasing depolarizing currents lead to action potential of decreasing amplitude
      and increasing half width, often terminated by a depolarization block. The
      presence of membrane excitability, the high density of CR cells in layer 1, their
      long-range horizontal axonal projection together with a high density of synaptic
      boutons and their synaptic input-output relationship suggest that they are an
      integral part of an early cortical network important not only in layer 1 but also
      for the establishment and formation of the cortical column. 

PMID- 24026290
TI  - Computational simulation of temperature elevations in tumors using Monte Carlo
      method and comparison to experimental measurements in laser photothermal therapy.
AB  - Accurate simulation of temperature distribution in tumors induced by gold
      nanorods during laser photothermal therapy relies on precise measurements of
      thermal, optical, and physiological properties of the tumor with or without
      nanorods present. In this study, a computational Monte Carlo simulation algorithm
      is developed to simulate photon propagation in a spherical tumor to calculate
      laser energy absorption in the tumor and examine the effects of the absorption
      (MU(a)) and scattering (MU(s)) coefficients of tumors on the generated heating
      pattern in the tumor. The laser-generated energy deposition distribution is then
      incorporated into a 3D finite-element model of prostatic tumors embedded in a
      mouse body to simulate temperature elevations during laser photothermal therapy
      using gold nanorods. The simulated temperature elevations are compared with
      measured temperatures in PC3 prostatic tumors in our previous in vivo
      experimental studies to extract the optical properties of PC3 tumors containing
      different concentrations of gold nanorods. It has been shown that the total laser
      energy deposited in the tumor is dominated by MU(a), while both MU(a) and MU(s)
      shift the distribution of the energy deposition in the tumor. Three sets of MU(a)
      and MU(s) are extracted, representing the corresponding optical properties of PC3
      tumors containing different concentrations of nanorods to laser irradiance at 808
      nm wavelength. With the injection of 0.1 cc of a 250 optical density (OD) nanorod
      solution, the total laser energy absorption rate is increased by 30% from the
      case of injecting 0.1 cc of a 50 OD nanorod solution, and by 125% from the
      control case without nanorod injection. Based on the simulated temperature
      elevations in the tumor, it is likely that after heating for 15 min, permanent
      thermal damage occurs in the tumor injected with the 250 OD nanorod solution,
      while thermal damage to the control tumor and the one injected with the 50 OD
      nanorod solution may be incomplete.

PMID- 24026291
TI  - Cytotoxic effects of mistletoe (Viscum album L.) in head and neck squamous cell
      carcinoma cell lines.
AB  - Head and neck squamous cell carcinoma is a complex disease with several etiologic
      factors and different molecular changes that may trigger certain events; it is
      also globally one of the most common malignancies in this topography. Extracts
      from Viscum album L. (VA) (mistletoe) have been used as adjuvant therapies with
      promising results in several types of cancer, mainly in European countries. In
      vitro studies have demonstrated that various types of VA may have cytotoxicity in
      carcinoma cells, activating the apoptotic cascade or leading cells to necrosis.
      This study aimed to verify the effects of three types of VA extracts (Iscador Qu
      Spezial, Iscador P and Iscador M) in squamous cell carcinoma of the tongue cell
      lines SCC9 and SCC25, not previously studied. A concentration of 0.3 mg/ml (IC50)
      of the drugs induced apoptosis, affecting gene expression and protein levels of
      AKT, PTEN and CYCLIN D1. It was concluded that VA extracts have a cytotoxic
      effect on SCC9 and SCC25 cell lines, but while SCC9 cell line was more resistant
      to the action of the drugs, Iscador Qu Spezial and Iscador M have higher
      cytotoxic potential in both cell lines compared to Iscador P. 

PMID- 24026292
TI  - Virucidal effect of acidic electrolyzed water and neutral electrolyzed water on
      avian influenza viruses.
AB  - The virucidal effects of two types of electrolyzed water, acidic electrolyzed
      water (AEW) and neutral electrolyzed water (NEW), on avian influenza viruses were
      studied. Virus titers of the highly pathogenic H5N1 virus and the low-pathogenic
      H9N2 virus irreversibly decreased by >5-log at 1 min after the viruses were mixed
      with NEW containing >=43 ppm free available chlorine (FAC), but not with NEW
      containing <17 ppm FAC. The minimum concentration of FAC for a virucidal effect
      of NEW was estimated at around 40 ppm. In contrast, the virus titers decreased by
      >5 log at 1 min after the viruses were mixed with AEW, in which the concentration
      of the FAC ranged from 72 to 0 ppm. Thus, the virucidal effect of AEW did not
      depend on the presence of FAC. Reverse transcription polymerase chain reaction
      amplified fragments of the M and NP genes, but not the complete M gene, from RNA
      extracted from the AEW-inactivated virus. Moderate morphological changes were
      found under the electron microscope, although no changes were observed in the
      electrophoresed proteins of the AEW-inactivated virus. No viral genes were
      amplified from the RNA extracted from the NEW-inactivated virus, regardless of
      the length of the targeted genes. No viral particles were detected under the
      electron microscope and no viral proteins were detected by electrophoresis for
      the NEW-inactivated virus. Thus, this study demonstrated potent virucidal effects
      of AEW and NEW and differences in the virucidal mechanism of the two types of
      electrolyzed water. 

PMID- 24026293
TI  - Small RNAs: emerging key players in DNA double-strand break repair.
AB  - DNA double-strand break (DSB) is the most deleterious form of DNA damage and
      poses great threat to genome stability. Eukaryotes have evolved complex
      mechanisms to repair DSBs through coordinated actions of protein sensors,
      transducers, and effectors. DSB-induced small RNAs (diRNAs) or Dicer/Drosha
      dependent RNAs (DDRNAs) have been recently discovered in plants and vertebrates,
      adding an unsuspected RNA component into the DSB repair pathway. DiRNAs/DDRNAs
      control DNA damage response (DDR) activation by affecting DDR foci formation and
      cell cycle checkpoint enforcement and are required for efficient DSB repair.
      Here, we summarize the findings of diRNAs/DDRNAs and discuss the possible
      mechanisms through which they act to facilitate DSB repair.

PMID- 24026294
TI  - Effects of diagnostic ultrasound on HSP70 expression in chorionic villi in rats
      during early pregnancy and the role of HSP70 in apoptosis in chorionic villi.
AB  - The aim of this study was to investigate the effects of diagnostic ultrasound on
      chorionic villi during early pregnancy in rats through the examination of heat
      shock protein 70 (HSP70) expression and apoptosis in chorionic villi. Using
      TUNEL, RT-PCR, western blot analysis and immunohistochemistry, the extent of
      apoptosis and the gene/protein expression of HSP70, Bcl-2 and Bax was determined
      in the samples of the chorionic villus from the rats during early pregnancy.
      Compared with the unexposed group, there were clear signs that apoptosis had
      occurred in the villi exposed to ultrasound for 30 min. The expression of HSP70
      and Bax in the villi gradually increased with the extended duration of exposure
      to ultrasound, whereas the expression of Bcl-2 gradually decreased. Bcl-2
      expression did not differ significantly between the group exposed for 10 min and
      the group exposed for 20 min. Taken together, our data demonstrate that HSP70 may
      protect chorionic villi exposed to ultrasound by inhibiting apoptosis; however,
      its protective effects are limited over the extended duration of exposure to
      ultrasound. Thus, the prudent use of ultrasound during the early stages of
      pregnancy should be advocated.

PMID- 24026295
TI  - Body position changes redistribute lung computed-tomographic density in patients
      with acute respiratory failure: impact and clinical fallout through the following
      20 years.
AB  - In patients with acute respiratory distress syndrome (ARDS), in supine position,
      there is a decrease of inflation along the sternum vertebral axis, up to lung
      collapse. In 1991 we published a report showing that, in ARDS patients, shifting
      from supine to prone position led immediately to the inversion of the inflation
      gradient and to a redistribution of densities from dorsal to ventral lung
      regions. This led to a "sponge model" as a wet sponge, similar to a heavy
      edematous lung, squeezes out the gas in the most dependent regions, due to the
      weight-related increase of the compressive forces. The sponge model accounts for
      density distribution in prone position, for which the unloaded dorsal regions are
      recruited, while the loaded ventral region, collapses. In addition, the sponge
      model accounts for the mechanism through which the positive end-expiratory
      pressure acts as counterforce to oppose the collapsing, compressing forces. The
      final result of proning was that the inversion of gravitational forces, together
      with other factors such as lung-chest wall shape-matching and the heart weight
      led to a more homogeneous distribution of inflation throughout the lung
      parenchyma. This is associated with oxygenation improvement as the dorsal
      recruitment, for anatomical reasons, prevails on the ventral de-recruitment. The
      more homogeneous distribution of inflation (i.e. of stress and strain)
      decreases/prevents the ventilator-induced lung injury, as consistently shown in
      animal experiments. Finally, and a series of clinical trials led to the
      conclusion that in patients with severe ARDS, the prone position provides a
      significant survival advantage. 

PMID- 24026296
TI  - Ultrasound-guided central venous cannulation is superior to quick-look ultrasound
      and landmark methods among inexperienced operators: a prospective randomized
      study.
AB  - OBJECTIVE: Quick-look ultrasound with a skin mark (UM) has been frequently used
      for central vein cannulation. The aim of this study is to compare this method
      with landmark (LM) and ultrasound-guided (UG) cannulation of jugular and femoral
      veins by inexperienced operators. DESIGN: Prospective randomized single-center
      study. SETTING: A medical intensive care unit (ICU) of a university medical
      center. PATIENTS: Patients requiring jugular or femoral central cannula
      placement. INTERVENTION: Each inexperienced resident randomly inserted a central
      venous line using the UM, LM or UG technique. MEASUREMENTS AND FINDINGS: The
      primary outcome was the success rate, and secondary outcomes were the placement
      time, number of attempts, mechanical complication rate, and catheter colonization
      rate. A total of 118 patients were randomly assigned to the three groups. The
      mean age of patients included in the study was 65 +/- 15 years, and the mean
      Simplified Acute Physiology Score 2 (SAPS2) was 57 +/- 20. The success rate was
      higher in the UG group than in the LM and UM groups (100, 74, and 73 %,
      respectively; p = 0.01). The total number of mechanical complications was higher
      in the LM and UM groups than in the UG group (24 and 36 versus 0 %, respectively;
      p = 0.01). The number of attempts and the access time were higher in the LM group
      than in the UG group, but not compared with the UM group. No difference in terms
      of catheter colonization was observed between the three groups. CONCLUSIONS:
      Ultrasound-guided cannulation of the internal jugular or femoral vein by
      inexperienced residents appears to be more reliable than the LM or UM methods and
      was associated with a lower mechanical complication rate among ICU patients.

PMID- 24026298
TI  - Increasing the effective airway diameter on weaning of tracheostomized patients:
      choosing the right outcome.

PMID- 24026297
TI  - De-escalation of empirical therapy is associated with lower mortality in patients
      with severe sepsis and septic shock.
AB  - PURPOSES: We set out to assess the safety and the impact on in-hospital and 90
      day mortality of antibiotic de-escalation in patients admitted to the ICU with
      severe sepsis or septic shock. METHODS: We carried out a prospective
      observational study enrolling patients admitted to the ICU with severe sepsis or
      septic shock. De-escalation was defined as discontinuation of an antimicrobial
      agent or change of antibiotic to one with a narrower spectrum once culture
      results were available. To control for confounding variables, we performed a
      conventional regression analysis and a propensity score (PS) adjusted
      multivariable analysis. RESULTS: A total of 712 patients with severe sepsis or
      septic shock at ICU admission were treated empirically with broad-spectrum
      antibiotics. Of these, 628 were evaluated (84 died before cultures were
      available). De-escalation was applied in 219 patients (34.9%). By multivariate
      analysis, factors independently associated with in-hospital mortality were septic
      shock, SOFA score the day of culture results, and inadequate empirical
      antimicrobial therapy, whereas de-escalation therapy was a protective factor
      [Odds-Ratio (OR) 0.58; 95% confidence interval (CI) 0.36-0.93). Analysis of the
      403 patients with adequate empirical therapy revealed that the factor associated
      with mortality was SOFA score on the day of culture results, whereas de
      escalation therapy was a protective factor (OR 0.54; 95% CI 0.33-0.89). The PS
      adjusted logistic regression models confirmed that de-escalation therapy was a
      protective factor in both analyses. De-escalation therapy was also a protective
      factor for 90-day mortality. CONCLUSIONS: De-escalation therapy for severe sepsis
      and septic shock is a safe strategy associated with a lower mortality. Efforts to
      increase the frequency of this strategy are fully justified.

PMID- 24026299
TI  - Heading in football, long-term cognitive decline and dementia: evidence from
      screening retired professional footballers.
AB  - BACKGROUND: Heading impairs cognition in the short and medium-terms; however,
      little is known about the long-term consequences. This study aimed to investigate
      the hypothesis that chronic low-level head trauma is associated with persistent
      cognitive decline. METHODS: All members of Former Player Associations (FPAs) from
      four professional football clubs in the UK were contacted to participate in the
      study. Participants were required to complete a self-assessed test of cognition,
      the Test Your Memory questionnaire. Further information was collected from
      respondents in order to analyse the potential effect of a number of variables on
      cognition. RESULTS: 10 of 92 respondents (10.87%) screened positive for possible
      mild cognitive impairment (MCI) or dementia. There was no association between low
      risk and high-risk playing positions (HR = 0.40, p = 0.456) or length of playing
      career (HR = 1.051 95% CI 0.879 to 1.257, p = 0.586) and a positive screening
      result. Age was a risk factor (HR = 1.137 per additional year, 95% CI 1.030 to
      1.255, p < 0.05), although this was not significantly different from the
      population prevalence across age groups. CONCLUSIONS: These results suggest that
      once a player ends their playing career, their risk of harm falls in line with
      the population, suggesting either that changes are reversible or that heading may
      not be as harmful as commonly thought. Future longitudinal studies of large
      numbers of professional football players are needed to support the findings from
      this study.

PMID- 24026300
TI  - Inflammation-induced proteolytic processing of the SIRPalpha cytoplasmic ITIM in
      neutrophils propagates a proinflammatory state.
AB  - Signal regulatory protein alpha (SIRPalpha), an immunoreceptor tyrosine-based
      inhibitory motif (ITIM)-containing receptor, is an essential negative regulator
      of leukocyte inflammatory responses. Here we report that SIRPalpha cytoplasmic
      signalling ITIMs in neutrophils are cleaved during active inflammation and that
      the loss of SIRPalpha ITIMs enhances the polymorphonuclear leukocyte (PMN)
      inflammatory response. Using human leukocytes and two inflammatory models in
      mice, we show that the cleavage of SIRPalpha ITIMs in PMNs but not monocytes
      occurs at the post-acute stage of inflammation and correlates with increased PMN
      recruitment to inflammatory loci. Enhanced transmigration of PMNs and PMN
      associated tissue damage are confirmed in mutant mice expressing SIRPalpha but
      lacking the ITIMs. Moreover, the loss of SIRPalpha ITIMs in PMNs during colitis
      is blocked by an anti-interleukin-17 (IL-17) antibody. These results demonstrate
      a SIRPalpha-based mechanism that dynamically regulates PMN inflammatory responses
      by generating a CD47-binding but non-signalling SIRPalpha 'decoy'. 

PMID- 24026301
TI  - Access to care outcomes: a telephone interview study of a suburban safety net
      program for the uninsured.
AB  - Access DuPage (AD) currently provides primary care for about 14,000 low income,
      uninsured residents of suburban DuPage County, IL, an area with a very limited
      healthcare safety net infrastructure. A telephone interview survey evaluated
      health care utilization, satisfaction, and health status outcomes and compared
      recent enrollees to individuals in the program for at least 1 year. Sequential
      new AD enrollees (n = 158) were asked about the previous year when uninsured,
      while randomly selected established AD enrollees (n = 135) were asked the same
      questions about the previous year when actively enrolled in AD. Established
      enrollees reported being more likely to get 'any kind of tests or treatment'
      (96.3 vs. 46.2 %, p < 0.0001), fewer cost (78.5 vs. 21.3 %, p < 0.0001) and
      transportation barriers to care, more preventive and mental health services, and
      better self-management care. However, established enrollees also reported 14 %
      greater use of hospital inpatient and 9 % greater use of emergency room care, as
      well as continued difficulty in accessing needed specialty and dental care
      services. Despite more (diagnosed) conditions, established enrollees were over
      2.5 times more likely to report good to excellent health status and over three
      times more likely to rate their satisfaction with health care as good to
      excellent. Findings illustrate the substantial benefits of assuring access to
      care for the uninsured, but do not reflect immediate savings from reduced
      hospital utilization. Access to care programs will be an important tool to
      address the needs of the 30 million people who will continue to be uninsured in
      the United States. 

PMID- 24026302
TI  - Collective efficacy and obesity-related health behaviors in a community sample of
      African Americans.
AB  - The social environment is important to body mass index and obesity. However, it
      is unknown if perceptions of the social environment are associated with obesity
      related behaviors in populations at greatest risk for being overweight or obese.
      We evaluated the relationship between collective efficacy and diet and physical
      activity in a community-based sample of African American adults who were
      residents in an urban area. Data were collected as part of an academic-community
      partnership from November 2009 to 2011. We evaluated whether participants met the
      recommended guidelines for diet and physical activity based on collective
      efficacy and their sociodemographic background, health care variables, and self
      efficacy in a community-based sample of African American adults (n = 338) who
      were residents in the Philadelphia, PA metropolitan area. Overall, many
      participants did not meet the recommended guidelines for fruit and vegetable
      intake or physical activity. The likelihood of meeting the recommended guidelines
      for fruit intake increased with greater levels of collective efficacy (OR 1.56,
      95 % CI 1.18, 2.07, p = 0.002) and self-efficacy for diet (OR 1.56, 95 % CI 1.19,
      2.04, p = 0.001). Collective efficacy was not associated with physical activity
      and the positive association between collective efficacy and vegetable intake was
      not statistically significant (OR 1.25, 95 % CI 0.94, 1.65, p = 0.12). It is
      important to determine the most effective methods and settings for improving diet
      and physical activity behaviors in urban African Americans. Enhancing collective
      efficacy may be important to improving adherence to recommended guidelines for
      obesity-related health behaviors. 

PMID- 24026303
TI  - Correlates of perceived risk of developing cancer among African-Americans in
      South Los Angeles.
AB  - There are differences in cancer-risk perception among racial/ethnic groups that
      may affect health risk behaviors. Using a community partnered-participatory
      research approach, we conducted a survey on cancer screening, risk behaviors, and
      related knowledge/attitudes within 11 churches in South Los Angeles with
      predominantly African-American parishioners. This analysis examines correlates of
      perceived risk of developing cancer among 755 African American adults. Almost 15
      % of participants indicated higher perceived risk for cancer compared to the
      average man/woman of the same age, 38 % indicated same risk, whereas 48 %
      perceived lower risk. Sixty-nine individuals (9 %) reported a cancer history and
      63 % reported at least one blood relative with cancer. Controlling for
      demographic characteristics and healthcare access, participants who reported
      higher risk of cancer had higher level of cancer-related knowledge; were current
      and ex-smokers; had poorer health status; had a blood relative with cancer; had a
      cancer history; and had discussed their risk of cancer with their doctor. The
      bivariate association between high perceived cancer risk and lack of exercise and
      obesity disappeared after adjusting for demographic characteristics and perceived
      health status. Our data suggest that a substantial proportion of African
      Americans in South Los Angeles may underestimate their cancer risk. Additionally,
      lack of exercise and obesity are not recognized as independent cancer risk
      factors as much as smoking and personal and family history of cancer. Next steps
      will be to inform participating churches about our findings and explore their
      interest in taking steps to reduce health risk behaviors among their
      parishioners. 

PMID- 24026305
TI  - Management of benign tracheal strictures caused by tracheostomy.
AB  - PURPOSE: To evaluate the clinical efficacy and safety of radiologic management
      for the treatment of benign tracheal strictures caused by tracheostomy. MATERIALS
      AND METHODS: We retrospectively reviewed of 13 patients with benign tracheal
      stricture caused by tracheostomy that was treated with balloon dilation or stent
      placement. Balloon dilation had initially been performed. Stent placement was
      indicated in patients who showed a poor response to balloon dilation. Outcomes
      were assessed according to the following variables: technical and clinical
      success, Hugh-Jones classification scale before and after the procedures, and
      complications. RESULTS: Balloon dilation and stent placement were technically
      successful in all patients. Nine of the 13 patients (69 %) showed no response to
      balloon dilation, and the remaining the four patients showed a positive response
      to initial balloon dilation. Six of the nine (67 %) patients showed a good
      response to temporary stent placement and required no further treatment. Mean
      Hugh-Jones grades improved from 3.6 +/- 0.8 to 1.8 +/- 1.1 (P < 0.001). During a
      follow-up period of 2.6-40.8 months (mean 16.5), overall clinical success was
      achieved in 10 patients (77 %) after a single balloon dilation (n = 4) and
      temporary stent placement (n = 6). The remaining three patients with clinical
      failure underwent tracheal resection (n = 3). CONCLUSION: Radiologic management
      can be a safe and effective therapeutic option for treating benign tracheal
      stricture caused by tracheostomy. Temporary stent placement can be effective in
      patients with symptoms recurring soon after balloon dilation.

PMID- 24026304
TI  - Mapping nonrecombining regions in barley using multicolor FISH.
AB  - Fluorescence in situ hybridization (FISH) is a widely used method to localize DNA
      sequences on chromosomes. Out of the many uses, FISH facilitates construction of
      physical maps by ordering contigs of large-insert DNA clones, typically bacterial
      artificial chromosome (BAC) and establishing their orientation. This is important
      in genomic regions with low recombination frequency where genetic maps suffer
      from poor resolution. While BAC clones can be mapped directly by FISH in plants
      with small genomes, excess of repetitive DNA hampers this application in species
      with large genomes. Mapping single-copy sequences such as complementary DNA
      (cDNA) is an attractive alternative. Unfortunately, localization of single-copy
      sequences shorter than 10 kb remains a challenging task in plants. Here, we
      present a highly efficient FISH technique that enables unambiguous localization
      of single copy genes. We demonstrated its utility by mapping 13 out of 15 full
      length cDNAs of variable length (2,127-3,400 bp), which were genetically defined
      to centromeric and pericentromeric regions of barley chromosome 7H. We showed
      that a region of 1.2 cM (0.7 %) on genetic map represented more than 40 % of the
      physical length of the chromosome. Surprisingly, all cDNA probes occasionally
      revealed hybridization signals on other chromosomes, indicating the presence of
      partially homologous sequences. We confirmed the order of 10 cDNA clones and
      suggested a different position for three cDNAs as compared to published genetic
      order. These results underline the need for alternative approaches such as FISH,
      which can resolve the order of markers in genomic regions where genetic mapping
      fails.

PMID- 24026306
TI  - Novel approach for juxtarenal aortic occlusion treatment: the Y-guidewire
      configuration for aortic bifurcation reconstruction.

PMID- 24026307
TI  - A comparison of phenotype definitions for diabetes mellitus.
AB  - OBJECTIVE: This study compares the yield and characteristics of diabetes cohorts
      identified using heterogeneous phenotype definitions. MATERIALS AND METHODS:
      Inclusion criteria from seven diabetes phenotype definitions were translated into
      query algorithms and applied to a population (n=173 503) of adult patients from
      Duke University Health System. The numbers of patients meeting criteria for each
      definition and component (diagnosis, diabetes-associated medications, and
      laboratory results) were compared. RESULTS: Three phenotype definitions based
      heavily on ICD-9-CM codes identified 9-11% of the patient population. A broad
      definition for the Durham Diabetes Coalition included additional criteria and
      identified 13%. The electronic medical records and genomics, NYC A1c Registry,
      and diabetes-associated medications definitions, which have restricted or no ICD
      9-CM criteria, identified the smallest proportions of patients (7%). The
      demographic characteristics for all seven phenotype definitions were similar (56
      57% women, mean age range 56-57 years).The NYC A1c Registry definition had higher
      average patient encounters (54) than the other definitions (range 44-48) and the
      reference population (20) over the 5-year observation period. The concordance
      between populations returned by different phenotype definitions ranged from 50 to
      86%. Overall, more patients met ICD-9-CM and laboratory criteria than medication
      criteria, but the number of patients that met abnormal laboratory criteria
      exclusively was greater than the numbers meeting diagnostic or medication data
      exclusively. DISCUSSION: Differences across phenotype definitions can potentially
      affect their application in healthcare organizations and the subsequent
      interpretation of data. CONCLUSIONS: Further research focused on defining the
      clinical characteristics of standard diabetes cohorts is important to identify
      appropriate phenotype definitions for health, policy, and research.

PMID- 24026308
TI  - The pattern of name tokens in narrative clinical text and a comparison of five
      systems for redacting them.
AB  - OBJECTIVE: To understand the factors that influence success in scrubbing personal
      names from narrative text. MATERIALS AND METHODS: We developed a scrubber, the
      NLM Name Scrubber (NLM-NS), to redact personal names from narrative clinical
      reports, hand tagged words in a set of gold standard narrative reports as
      personal names or not, and measured the scrubbing success of NLM-NS and that of
      four other scrubbing/name recognition tools (MIST, MITdeid, LingPipe, and
      ANNIE/GATE) against the gold standard reports. We ran three comparisons which
      used increasingly larger name lists. RESULTS: The test reports contained more
      than 1 million words, of which 2388 were patient and 20,160 were provider name
      tokens. NLM-NS failed to scrub only 2 of the 2388 instances of patient name
      tokens. Its sensitivity was 0.999 on both patient and provider name tokens and
      missed fewer instances of patient name tokens in all comparisons with other
      scrubbers. MIST produced the best all token specificity and F-measure for name
      instances in our most relevant study (study 2), with values of 0.997 and 0.938,
      respectively. In that same comparison, NLM-NS was second best, with values of
      0.986 and 0.748, respectively, and MITdeid was a close third, with values of
      0.985 and 0.796 respectively. With the addition of the Clinical Center name list
      to their native name lists, Ling Pipe, MITdeid, MIST, and ANNIE/GATE all improved
      substantially. MITdeid and Ling Pipe gained the most--reaching patient name
      sensitivity of 0.995 (F-measure=0.705) and 0.989 (F-measure=0.386), respectively.
      DISCUSSION: The privacy risk due to two name tokens missed by NLM-NS was
      statistically negligible, since neither individual could be distinguished among
      more than 150,000 people listed in the US Social Security Registry. CONCLUSIONS:
      The nature and size of name lists have substantial influences on scrubbing
      success. The use of very large name lists with frequency statistics accounts for
      much of NLM-NS scrubbing success.

PMID- 24026309
TI  - Is a positive family history of endometriosis a risk factor for endometrioma
      recurrence after laparoscopic surgery?
AB  - A total of 148 patients were followed up for an average of 30.1 +/- 17 months
      following to laparoscopic excision of ovarian endometriomas by a single surgical
      team. Bivariate and multivariate analyses were used to investigate the
      association between endometrioma recurrence and several factors, age, body mass
      index, family history, cyst diameter, number and location, adhesions or
      peritoneal implants, occurrence of spillage, postoperative treatment with
      gonadotropin-releasing hormone agonist, or pregnancies. The overall recurrence
      rate of the endometriomas was 18.2%. At bivariate analysis, recurrence rate was
      significantly higher in patients with a positive family history of endometriosis
      (40% vs 14.8%). Recurrence was also more frequent, albeit nonsignificantly, in
      patients with a history of dysmenorrhea, intraoperative spillage, and
      postoperative hormonal suppression. At multivariate analysis with logistic
      regression, a positive family history of endometriosis was the only variable
      independently associated with endometrioma recurrence following laparoscopic
      removal (odds ratio 3.245; 95% confidence interval: 1.090-9.661). 

PMID- 24026310
TI  - TREM-1 expression is increased in human placentas from severe early-onset
      preeclamptic pregnancies where it may be involved in syncytialization.
AB  - Preeclampsia, a major cause of maternal and perinatal morbidity and mortality, is
      thought to be attributable to dysregulation of trophoblast invasion and
      differentiation. Microarray studies have shown that triggering receptor expressed
      on myeloid cells (TREM) 1, a cell surface molecule involved in the inflammatory
      response, is increased in preeclamptic placentas. The aim of this study was to
      determine the level of TREM-1 expression in severe early-onset preeclamptic
      placentas and its functional role in trophoblast differentiation. Placenta was
      obtained from women with severe early-onset preeclampsia (n = 19) and
      gestationally matched preterm controls placentas (n = 8). The TREM-1 expression
      was determined by quantitative reverse transcriptase polymerase chain reaction
      and Western blotting. The effect of TREM-1 small interfering RNA on cell fusion
      and differentiation was assessed in BeWo cells. The effect of oxygen tension on
      TREM-1 levels, in basal or forskolin-treated BeWo cells, was also assessed. The
      TREM-1 was localized to the syncytiotrophoblast layer, and TREM-1 messenger RNA
      and protein expression was significantly increased in preeclamptic placentas. The
      BeWo cells treated with forskolin were associated with increased TREM-1
      expression. The TREM-1 knockdown inhibited forskolin-induced expression of the
      differentiation marker beta-human chorionic gonadotropin but had no effect on the
      cell-fusion marker E-cadherin. The increase in TREM-1 expression in BeWo cells
      treated with forskolin during normoxic conditions was reduced in forskolin
      treated cells under hypoxic conditions. In conclusion, TREM-1 is increased in
      preeclamptic placentas and by forskolin treatment. Knockdown of TREM-1 by RNA
      interference inhibits cell differentiation but has no effect on cell-cell fusion.
      Finally, we show that TREM-1 upregulation is attenuated under hypoxic conditions
      in which cell differentiation is impaired. 

PMID- 24026313
TI  - Invited commentary: fracture follow-up program in an open healthcare system.
AB  - The basis of the Fracture Liaison Service is to identify and treat those patients
      at highest risk of suffering a second fracture. The execution of this type of
      program poses unique challenges in open healthcare settings that lack a central
      coordination of patient care. This invited editorial reviews the establishment
      and operation of The Marian Osteoporosis Center at Marian Medical Center in Santa
      Maria, California. 

PMID- 24026311
TI  - Large conductance Ca2+-activated K+ channels modulate uterine alpha1-adrenergic
      sensitivity in ovine pregnancy.
AB  - The uteroplacental vasculature is refractory to alpha-adrenergic stimulation, and
      large conductance Ca(2+)-activated K(+) channels (BK(Ca)) may contribute. We
      examined the effects of uterine artery (UA) BK(Ca) inhibition with
      tetraethylammonium (TEA) on hemodynamic responses to phenylephrine (PE) at 101 to
      117 days and 135 to 147 days of ovine gestation, obtaining dose responses for
      mean arterial pressure (MAP), heart rate (HR), and uteroplacental blood flow
      (UPBF) and vascular resistance (UPVR) before and during UA TEA infusions. The UA
      alpha(1)-adrenergic receptors (alpha1-ARs) were assessed. The PE increased MAP
      and UPVR and decreased HR and UPBF dose dependently at both gestations (P < .001,
      analysis of variance). The %?MAP was less at 135 to 147 days before and during
      TEA infusions (P <= .008); however, responses during TEA were greater (P <=
      .002). The PE increased %?UPVR>>%?MAP, thus %?UPBF fell. The TEA enhanced PE
      mediated increases in %?UPVR at 135 to 147 days (P <= .03). The UA alpha(1)-AR
      expression was unchanged in pregnancy. Uterine vascular responses to PE exceed
      systemic vascular responses throughout pregnancy and are attenuated by BK(Ca)
      activation, suggesting BK(Ca) protect UPBF.

PMID- 24026312
TI  - Fracture Liaison Services in an open system: how was it done? what were the
      barriers and how were they overcome?
AB  - A fragility fracture signals the potential for the occurrence of a subsequent
      fracture, and it often represents the first opportunity for care of osteoporosis.
      It is now well accepted knowledge that fracture liaison services can close or, at
      the very least, narrow the care gap that exists in the management of these
      sentinel events in patients with osteoporosis. The challenge, however, lies in
      translating this knowledge into practice and to implement these programs in
      health care systems with varied infrastructure and delivery practices operating
      in varied geographical environments. A review of a functioning model of care in
      an open health system in an Asian country and a short account of the problems
      encountered and the lessons learned during the course of its implementation are
      provided. 

PMID- 24026314
TI  - Fracture Liaison Services in the United Kingdom.
AB  - Fracture Liaison Services (FLS) have been demonstrated to be a clinically and
      cost-effective means of providing secondary preventive care for patients
      presenting with new fragility fractures. This review summarizes the emergence and
      widespread adoption of the FLS model in the United Kingdom. Large scale national
      audits have clearly illustrated the need for FLS by revealing the care gap
      experienced by the majority of patients who suffer fragility fractures. Since
      2003, FLS has featured increasingly more prominently in relevant national
      professional guidance. During the last 5 years that professional consensus has
      led to FLS being embedded in government policy on fracture prevention. Quality
      incentives have been created to encourage hospitals and primary care providers to
      pro-actively deliver best practice. The strategic approaches taken and lessons
      learned in the UK may have relevance to quality improvement efforts in other
      jurisdictions. 

PMID- 24026315
TI  - THD Doppler procedure for hemorrhoids: the surgical technique.
AB  - Transanal hemorrhoidal dearterialization (THD) is an effective treatment for
      hemorrhoidal disease. The ligation of hemorrhoidal arteries (called
      "dearterialization") can provide a significant reduction of the arterial overflow
      to the hemorrhoidal piles. Plication of the redundant rectal mucosa/submucosa
      (called "mucopexy") can provide a repositioning of prolapsing tissue to the
      anatomical site. In this paper, the surgical technique and perioperative patient
      management are illustrated. Following adequate clinical assessment, patients
      undergo THD under general or spinal anesthesia, in either the lithotomy or the
      prone position. In all patients, distal Doppler-guided dearterialization is
      performed, providing the selective ligation of hemorrhoidal arteries identified
      by Doppler. In patients with hemorrhoidal/muco-hemorrhoidal prolapse, the
      mucopexy is performed with a continuous suture including the redundant and
      prolapsing mucosa and submucosa. The description of the surgical procedure is
      complemented by an accompanying video (see supplementary material). In long-term
      follow-up, there is resolution of symptoms in the vast majority of patients. The
      most common complication is transient tenesmus, which sometimes can result in
      rectal discomfort or pain. Rectal bleeding occurs in a very limited number of
      patients. Neither fecal incontinence nor chronic pain should occur. Anorectal
      physiology parameters should be unaltered, and anal sphincters should not be
      injured by following this procedure. When accurately performed and for the
      correct indications, THD is a safe procedure and one of the most effective
      treatments for hemorrhoidal disease. 

PMID- 24026316
TI  - Methylprednisolone injections for the carpal tunnel syndrome: a randomized,
      placebo-controlled trial.
AB  - BACKGROUND: Steroid injections are used in idiopathic carpal tunnel syndrome
      (CTS), but evidence of efficacy beyond 1 month is lacking. OBJECTIVE: To assess
      the efficacy of local methylprednisolone injections in CTS. DESIGN: Randomized,
      placebo-controlled trial. (ClinicalTrials.gov: NCT00806871). SETTING: Regional
      referral orthopedic department in Sweden. PATIENTS: Patients aged 18 to 70 years
      with CTS but no previous steroid injections. INTERVENTION: Three groups (37
      patients each) received 80 mg of methylprednisolone, 40 mg of methylprednisolone,
      or placebo. The patients and treating surgeons were blinded. MEASUREMENTS:
      Primary end points were the change in CTS symptom severity scores at 10 weeks
      (range, 1 to 5) and rate of surgery at 1 year. Three patients had missing 10-week
      data. All patients had 1-year data. RESULTS: Improvement in CTS symptom severity
      scores at 10 weeks was greater in patients who received 80 mg of
      methylprednisolone and 40 mg of methylprednisolone than in those who received
      placebo (difference in change from baseline, -0.64 [95% CI, -1.06 to -0.21; P =
      0.003] and -0.88 [CI, -1.30 to -0.46; P < 0.001], respectively), but there were
      no significant differences at 1 year. The 1-year rates of surgery were 73%, 81%,
      and 92% in the 80-mg methylprednisolone, 40-mg methylprednisolone, and placebo
      groups, respectively. Compared with patients who received placebo, those who
      received 80 mg of methylprednisolone were less likely to have surgery (odds
      ratio, 0.24 [CI, 0.06 to 0.95]; P = 0.042). With time to surgery incorporated,
      both the 80- and 40-mg methylprednisolone groups had lower likelihood of surgery
      (hazard ratio, 0.46 [CI, 0.27 to 0.77; P = 0.003] and 0.57 [CI, 0.35 to 0.94; P =
      0.026], respectively). LIMITATION: The study was conducted at 1 center, and wrist
      splinting had previously failed for all patients. CONCLUSION: Methylprednisolone
      injections for CTS have significant benefits in relieving symptoms at 10 weeks
      and reducing the rate of surgery 1 year after treatment, but 3 out of 4 patients
      had surgery within 1 year. PRIMARY FUNDING SOURCE: Region of Scania Research and
      Development Foundation and Hassleholm Hospital Organization.

PMID- 24026317
TI  - Social networking technologies as an emerging tool for HIV prevention: a cluster
      randomized trial.
AB  - BACKGROUND: Social networking technologies are an emerging tool for HIV
      prevention. OBJECTIVE: To determine whether social networking communities can
      increase HIV testing among African American and Latino men who have sex with men
      (MSM). DESIGN: Randomized, controlled trial with concealed allocation.
      (ClinicalTrials.gov: NCT01701206). SETTING: Online. PATIENTS: 112 MSM based in
      Los Angeles, more than 85% of whom were African American or Latino. INTERVENTION:
      Sixteen peer leaders were randomly assigned to deliver information about HIV or
      general health to participants via Facebook groups over 12 weeks. After
      participants accepted a request to join the group, participation was voluntary.
      Group participation and engagement were monitored. Participants could request a
      free, home-based HIV testing kit and completed questionnaires at baseline and 12
      week follow-up. MEASUREMENTS: Participant acceptance of and engagement in the
      intervention and social network participation, rates of home-based HIV testing,
      and sexual risk behaviors. RESULTS: Almost 95% of intervention participants and
      73% of control participants voluntarily communicated using the social platform.
      Twenty-five of 57 intervention participants (44%) requested home-based HIV
      testing kits compared with 11 of 55 control participants (20%) (difference, 24
      percentage points [95% CI, 8 to 41 percentage points]). Nine of the 25
      intervention participants (36%) who requested the test took it and mailed it back
      compared with 2 of the 11 control participants (18%) who requested the test.
      Retention at study follow-up was more than 93%. LIMITATION: Only 2 Facebook
      communities were included for each group. CONCLUSION: Social networking
      communities are acceptable and effective tools to increase home-based HIV testing
      among at-risk populations. PRIMARY FUNDING SOURCE: National Institute of Mental
      Health.

PMID- 24026318
TI  - A prospective assessment defining the limitations of thyroid nodule pathologic
      evaluation.
AB  - BACKGROUND: Clinical management of thyroid neoplasms is based on light
      microscopic diagnosis, but its accuracy and precision are poorly defined.
      OBJECTIVE: To assess inter- and intraobserver variability of preoperative
      cytopathologic and postoperative histopathologic thyroid diagnoses. DESIGN:
      Samples were collected in a prospective, multicenter trial validating a gene
      expression classifier between June 2009 and December 2010. SETTING: 14 academic
      and 35 community clinical sites. PATIENTS: 653 patients with 776 surgically
      resected thyroid nodules of 1 cm or greater. MEASUREMENTS: Intraobserver
      concordance among 2 or more central histopathologists who independently read
      histopathology slides was calculated. Interobserver concordance between the
      diagnoses made by the central histopathologists and those made by local
      pathologists were calculated. Intra- and interobserver concordance for
      cytopathology was similarly calculated by comparing diagnoses made by local
      pathologists with those made by a central panel of 3 cytopathologists. RESULTS:
      Concordance on the histopathologic distinction between benign and malignant
      diagnoses was 91% comparing local with central histopathologists and 90%
      comparing 2 central histopathologists. Using the 6-category Bethesda System,
      64.0% of diagnoses made by local and central cytopathologists and 74.7% of
      intraobserver diagnoses were concordant. Central cytopathologists made fewer
      indeterminate diagnoses than local pathologists (41.2% vs. 55.0%). LIMITATIONS:
      Many local pathologists did not use the Bethesda System, so their reports were
      translated to allow comparison. The study required histopathology, and the study
      population and specimens did not encompass all newly evaluated patients with a
      thyroid nodule. CONCLUSION: Substantial inter- and intraobserver variability
      exists in the cytopathologic and histopathologic evaluation of thyroid nodules,
      confirming an inherent limitation of visual microscopic diagnosis. PRIMARY
      FUNDING SOURCE: Veracyte.

PMID- 24026319
TI  - The ankle-brachial index for peripheral artery disease screening and
      cardiovascular disease prediction among asymptomatic adults: a systematic
      evidence review for the U.S. Preventive Services Task Force.
AB  - BACKGROUND: Screening for peripheral artery disease (PAD) may reduce morbidity
      and mortality. PURPOSE: To review the evidence on the ability of the ankle
      brachial index (ABI) to predict cardiovascular disease (CVD) morbidity and
      mortality independent of Framingham Risk Score (FRS) factors in asymptomatic
      adults and on the benefits and harms of treating screen-detected adults with PAD.
      DATA SOURCES: MEDLINE and the Cochrane Central Register of Controlled Trials
      (1996 to September 2012), clinical trial registries, reference lists, and
      experts. STUDY SELECTION: English-language, population-based prognostic studies
      evaluating the ABI in addition to the FRS and treatment trials or studies of
      treatment harms in screen-detected adults with PAD. DATA EXTRACTION: Dual quality
      assessment and abstraction of relevant study details. DATA SYNTHESIS: One large
      meta-analysis (n = 43 919) showed that the ABI could reclassify 10-year risk for
      coronary artery disease (CAD), but it did not report measures of appropriate
      reclassification (the net reclassification improvement [NRI]). Four heterogeneous
      risk prediction studies showed that the magnitude of the NRI was probably small
      when the ABI was added to the FRS to predict CAD or CVD events. Of 2 treatment
      trials meeting inclusion criteria, 1 large trial (n = 3350) showed that low-dose
      aspirin did not prevent CVD events in persons with a screen-detected low ABI but
      may have increased the risk for major bleeding events. LIMITATIONS: Most
      prognostic studies did not allow for calculation of a bias-corrected NRI.
      Evidence on treatment benefits and harms was limited to aspirin and was scant.
      CONCLUSION: Adding the ABI to the FRS probably has limited value for predicting
      CAD or CVD. Treatment benefits for asymptomatic individuals with screen-detected
      PAD are not established. PRIMARY FUNDING SOURCE: Agency for Healthcare Research
      and Quality.

PMID- 24026320
TI  - Screening for peripheral artery disease and cardiovascular disease risk
      assessment with the ankle-brachial index in adults: U.S. Preventive Services Task
      Force recommendation statement.
AB  - DESCRIPTION: Update of the 2005 U.S. Preventive Services Task Force (USPSTF)
      recommendation on screening for peripheral artery disease (PAD). METHODS: The
      USPSTF reviewed the evidence on the use of resting ankle-brachial index (ABI) as
      a screening test for PAD or as a risk predictor for cardiovascular disease (CVD).
      The review focused on resting ABI as the sole screening method; the diagnostic
      performance of ABI testing in primary care populations, unselected populations,
      and asymptomatic populations; the predictive value of ABI testing for major CVD
      outcomes in primary care or unselected populations; and the effect of treatment
      on general CVD and PAD-specific morbidity in patients with asymptomatic or
      minimally symptomatic PAD. POPULATION: This recommendation applies to
      asymptomatic adults who do not have a known diagnosis of PAD, CVD, severe chronic
      kidney disease, or diabetes. RECOMMENDATION: The USPSTF concludes that the
      current evidence is insufficient to assess the balance of benefits and harms of
      screening for PAD and CVD risk assessment with the ABI in adults. (I statement).

PMID- 24026321
TI  - Ankle-brachial index screening to improve health outcomes: where is the evidence?

PMID- 24026322
TI  - A day in the life of a corporate retail pharmacist.

PMID- 24026325
TI  - Effect of age, tumor risk, and comorbidity in a U.S. population-based cohort of
      men with prostate cancer.

PMID- 24026326
TI  - Effect of age, tumor risk, and comorbidity in a u.s. Population-based cohort of
      men with prostate cancer.

PMID- 24026327
TI  - Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis
      C virus infection.

PMID- 24026328
TI  - Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis
      C virus infection.

PMID- 24026329
TI  - Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis
      C virus infection.

PMID- 24026332
TI  - Summaries for patients: steroid injections for the carpal tunnel syndrome.

PMID- 24026333
TI  - Summaries for patients: screening for peripheral artery disease and
      cardiovascular disease risk assessment with the ankle-brachial index: U.S.
      Preventive Services Task Force recommendation statement.

PMID- 24026334
TI  - Summaries for patients: screening for hepatitis C virus infection in adults: U.S.
      Preventive Services Task Force recommendation statement.

PMID- 24026335
TI  - In the clinic: obesity.

PMID- 24026336
TI  - Computational modeling of channelrhodopsin-2 photocurrent characteristics in
      relation to neural signaling.
AB  - Channelrhodopsins-2 (ChR2) are a class of light sensitive proteins that offer the
      ability to use light stimulation to regulate neural activity with millisecond
      precision. In order to address the limitations in the efficacy of the wild-type
      ChR2 (ChRwt) to achieve this objective, new variants of ChR2 that exhibit fast
      mon-exponential photocurrent decay characteristics have been recently developed
      and validated. In this paper, we investigate whether the framework of transition
      rate model with 4 states, primarily developed to mimic the biexponential
      photocurrent decay kinetics of ChRwt, as opposed to the low complexity 3 state
      model, is warranted to mimic the mono-exponential photocurrent decay kinetics of
      the newly developed fast ChR2 variants: ChETA (Gunaydin et al., Nature Neurosci.
      13:387-392, 2010) and ChRET/TC (Berndt et al., Proc. Natl. Acad. Sci. 108:7595
      7600, 2011). We begin by estimating the parameters of the 3-state and 4-state
      models from experimental data on the photocurrent kinetics of ChRwt, ChETA, and
      ChRET/TC. We then incorporate these models into a fast-spiking interneuron model
      (Wang and Buzsaki, J. Neurosci. 16:6402-6413, 1996) and a hippocampal pyramidal
      cell model (Golomb et al., J. Neurophysiol. 96:1912-1926, 2006) and investigate
      the extent to which the experimentally observed neural response to various
      optostimulation protocols can be captured by these models. We demonstrate that
      for all ChR2 variants investigated, the 4 state model implementation is better
      able to capture neural response consistent with experiments across wide range of
      optostimulation protocol. We conclude by analytically investigating the
      conditions under which the characteristic specific to the 3-state model, namely
      the monoexponential photocurrent decay of the newly developed variants of ChR2,
      can occur in the framework of the 4-state model. 

PMID- 24026337
TI  - Modeling the formaldehyde-graphene interaction using a formaldehyde-pyrene
      system.
AB  - Study of the dynamics of H2CO confined within graphene sheets and sensing of H2CO
      by graphene require an analytic representation of the intermolecular potential
      between H2CO and graphene. To develop an intermolecular potential for H2CO
      interacting with graphene, ab initio calculations were performed at the MP2/MG3S,
      B97-D/MG3S and LPNO-CEPA/1/CBS levels of theory using H2CO-pyrene as a model. The
      intermolecular interactions were computed for three different orientations of
      formaldehyde approaching pyrene for a complete description of the interaction.
      The interaction energy obtained from the MP2, B97-D and LPNO-CEPA/1 methods were
      compared with the CCSD(T) method. The LPNO-CEPA/1/CBS method gives the best
      interaction energies compared to the CCSD(T)/CBS method. The LPNO-CEPA/1/CBS data
      obtained is fitted to an analytical potential energy function written as the sum
      of two-body interactions between the C atoms of pyrene and the C, H, O atoms of
      formaldehyde. The fitted potential energy function represents the ab initio data
      in excellent agreement for all the orientations considered. The analytical
      potential was also found to represent very well the interactions for two new
      orientations not considered in fitting, emphasizing the global nature of the
      analytic potential. The new potential is also compared with the van der Waals
      AMBER model. 

PMID- 24026338
TI  - Papuamine causes autophagy following the reduction of cell survival through
      mitochondrial damage and JNK activation in MCF-7 human breast cancer cells.
AB  - We previously reported that extracts of an Indonesian marine sponge Haliclona sp.
      showed potent cytotoxicity and the induction of apoptosis against human solid
      cancer cell lines. In this study, we examine the cytotoxic mechanism of the major
      chemical compound, papuamine, on MCF-7 human breast cancer cells. Papuamine at 5
      uM did not show significant cytotoxic effects after incubation for 24 h, but
      autophagosome vesicular formation was apparent. At 10 uM of papuamine,
      significant reduction in cell survival was observed at 12 h, and increases in
      autophagy at this concentration were time-dependent and apparent before the
      appearance of cytotoxic effects. Both the release of cytochrome c to the cytosol
      and increase in Bax in the mitochondrial fraction were found to be concentration
      dependent. Moreover, mitochondrial membrane potential shows concentration- and
      time-dependent decreases with exposure to papuamine. The release of cytochrome c
      has been shown to be accompanied by an increase in JNK activation. 3
      Methyladenine (MA), a classical autophagy inhibitor showed increased JNK
      activation by exposure to papuamine. In conclusion, our results indicate that
      papuamine causes earlier onset autophagy and delayed reduction of cell survival
      through mitochondrial damage and JNK activation in MCF-7 cells.

PMID- 24026340
TI  - Happiness and the patterns of life: a study of geolocated tweets.
AB  - The patterns of life exhibited by large populations have been described and
      modeled both as a basic science exercise and for a range of applied goals such as
      reducing automotive congestion, improving disaster response, and even predicting
      the location of individuals. However, these studies have had limited access to
      conversation content, rendering changes in expression as a function of movement
      invisible. In addition, they typically use the communication between a mobile
      phone and its nearest antenna tower to infer position, limiting the spatial
      resolution of the data to the geographical region serviced by each cellphone
      tower. We use a collection of 37 million geolocated tweets to characterize the
      movement patterns of 180,000 individuals, taking advantage of several orders of
      magnitude of increased spatial accuracy relative to previous work. Employing the
      recently developed sentiment analysis instrument known as the hedonometer, we
      characterize changes in word usage as a function of movement, and find that
      expressed happiness increases logarithmically with distance from an individual's
      average location. 

PMID- 24026339
TI  - Predicting improvement of functioning in disability claimants.
AB  - PURPOSE: In the Netherlands, disability claimants are assessed after 2 years of
      sick leave, but their functioning may still improve. An accurate prognosis of
      functioning is difficult. Self predictions may be more accurate than those of
      professionals. The aim of this study, is to assess and compare the accuracy of
      predictions by disability claimants and insurance physicians (IPs) working at the
      Social Security Institute. It is further studied whether the accuracy differs
      between subgroups of claimants with mental or somatic health conditions. METHODS:
      We used data from the prospective cohort study cohort study. Following the
      assessment of the disability claim (n = 375) and after 1 year follow up (T1, n =
      276) data on functioning were obtained from respondents by self-report
      questionnaire World Health Organization Disability Schedule 2.0. Both claimants
      and IPs were asked to predict improvement of functioning. Accuracy of their
      predictions were assessed by sensitivity, specificity, and area under the
      receiver operating curves (AUC). Mixed logistic regression was conducted to
      explore differences in accuracy between claimants with mental and somatic
      conditions. RESULTS: One-third (32 %) of disability claimants improved beyond the
      standard error of measurement. Disability claimants' and IPs were able to predict
      this improvement of functioning, but to a limited extent, with an AUC of 0.61 for
      IPs and 0.62 for disability claimants. We found no statistically significant
      differences in the accuracy of the predictions in claimants with mental or
      somatic health conditions. CONCLUSIONS: Improvements of functioning were not
      uncommon. However, both IPs and disability claimants were unable to predict
      improvement with high levels of accuracy in both mental and somatic health
      conditions.

PMID- 24026341
TI  - Ice-pack dermatosis: a cold-induced dermatitis with similarities to cold
      panniculitis and perniosis that histopathologically resembles lupus.
AB  - IMPORTANCE: Cold panniculitis is a self-limited condition, manifesting as
      erythematous plaques or nodules after cold exposure, that typically affects
      infants and children. Recently, a variant involving the lateral thighs of
      equestrians has been described. Since the original report of this variant, some
      confusion has arisen in the literature in which the terms equestrian cold
      panniculitis and equestrian perniosis are both used. Outside of this
      presentation, cold panniculitis in adults is exceedingly rare. OBSERVATIONS: We
      describe 2 adult patients using ice-pack therapy for chronic back pain who
      developed erythematous, purpuric plaques at the site of ice-pack application.
      Histopathologic findings from both patients were similar and showed overlapping
      features of perniosis and cold panniculitis that closely resembled the pattern
      seen in cutaneous lupus erythematosus. CONCLUSIONS AND RELEVANCE: Ice-pack
      dermatosis is an uncommon cold-induced process that occurs in adults using long
      term ice-pack therapy. The clinical manifestations include erythematous to
      purpuric plaques with a livedolike appearance and superficial ulceration. The
      histopathologic features resemble those seen in cutaneous lupus erythematosus
      with a superficial and deep perivascular and periadnexal dermatitis with
      increased dermal mucin and a superficial lobular panniculitis.

PMID- 24026342
TI  - Dutch translation of the Kujala Anterior Knee Pain Scale and validation in
      patients after knee arthroplasty.
AB  - PURPOSE: To translate and validate the Kujala Anterior Knee Pain Scale (AKPS) in
      patients who have undergone total knee arthroplasty (TKA) or unicompartmental
      knee arthroplasty (UKA) and evaluate the internal consistency, construct validity
      and ceiling or floor effect. METHODS: After standard forward and backward
      translation was performed, 302 patients who have received a TKA or UKA filled out
      the AKPS together with Hospital for Special Surgery (HSS) patella score, visual
      analogue score (VAS) for pain, the Oxford 12-item questionnaire and the SF-36 at
      follow-up. The internal consistency was tested using Cronbach's alpha
      coefficient. The construct validity was assessed using Spearman's rank
      correlation (R) to test for correlations between the AKPS and VAS HSS, HSS
      patella score, VAS month, Oxford 12-item questionnaire and SF-36 subscales.
      Ceiling or floor effects are given in percentage of patients giving a maximum or
      minimum score. RESULTS: The internal reliability of the AKPS is acceptable with a
      Cronbach's alpha of 0.81 in patients after TKA or UKA. A high correlation was
      found between the AKPS and the Oxford 12-item questionnaire (R = 0.81). Moderate
      correlations were found with the VAS month (R = 0.63), HSS patella score (R =
      0.51) and SF-36 subscales physical functioning (R = 0.59), role-physical (R =
      0.59), bodily pain (R = 0.57). Other correlations were poor, therefore indicating
      a good convergent and divergent validity. Ceiling effects were observed for the
      HSS patella score (31 %), VAS HSS (51 %), VAS pain (19 %), SF36-RP (46 %), SF36
      RE (80 %) and SF36-BP (24 %). No ceiling or floor effect was found for the AKPS,
      Oxford 12-item and the other SF36 domains. CONCLUSIONS: The AKPS appears to be
      reliable and valid in patients after knee arthroplasty, with no ceiling and floor
      effects, and can be used to assess anterior knee pain in patient who underwent
      joint replacement surgery.

PMID- 24026343
TI  - A milestone in the doubled haploid pathway of cassava: a milestone in the doubled
      haploid pathway of cassava (Manihot esculenta Crantz): cellular and molecular
      assessment of anther-derived structures.
AB  - This study was aimed at inducing androgenesis in cultured anthers of cassava
      (Manihot esculenta Crantz) to develop a protocol for the production of doubled
      haploids. Microspore reprogramming was induced in cassava by cold or heat stress
      of anthers. Since the anthers contain both haploid microspores and diploid
      somatic cells, it was essential to verify the origin of anther-derived calli. The
      origin of anther-derived calli was assessed by morphological screening followed
      by histological analysis and flow cytometry (FCM). Additionally, simple sequence
      repeat (SSR) and amplified fragmented length polymorphism (AFLP) assays were used
      for the molecular identification of the microspore-derived calli. The study
      clearly demonstrated the feasibility of producing microspore-derived calli using
      heat- or cold-pretreated anthers. Histological studies revealed reprogramming of
      the developmental pathway of microspores by symmetrical division of the nucleus.
      Flow cytometry analysis revealed different ploidy level cell types including
      haploids, which confirmed their origin from the microspores. The SSR and AFLP
      marker assays independently confirmed the histological and FCM results of a
      haploid origin of the calli at the DNA level. The presence of multicellular
      microspores in the in vitro system indicated a switch of developmental program,
      which constitutes a crucial step in the design of protocols for the regeneration
      of microspore-derived embryos and plants. This is the first detailed report of
      calli, embryos, and abnormal shoots originated from the haploid cells in cassava,
      leading to the development of a protocol for the production of doubled haploid
      plants in cassava.

PMID- 24026344
TI  - Improved antibody production in Chinese hamster ovary cells by ATF4
      overexpression.
AB  - To improve antibody production in Chinese hamster ovary (CHO) cells, the
      humanized antibody-producing CHO DP-12-SF cell line was transfected with the gene
      encoding activating transcription factor 4 (ATF4), a central factor in the
      unfolded protein response. Overexpression of ATF4 significantly enhanced the
      production of antibody in the CHO DP-12-SF cell line. The specific IgG production
      rate of in the ATF4-overexpressing CHO-ATF4-16 cells was approximately 2.4 times
      that of the parental host cell line. Clone CHO-ATF4-16 did not show any change in
      growth rate compared with the parental cells or mock-transfected CHO-DP12-SF
      cells. The expression levels of mRNAs encoding both the antibody heavy and light
      chains in the CHO-ATF4-16 clone were analyzed. This analysis showed that ATF4
      overexpression improved the total production and specific production rate of
      antibody without affecting the mRNA transcription level. These results indicate
      that ATF4 overexpression is a promising method for improving recombinant IgG
      production in CHO cells. 

PMID- 24026345
TI  - Macroscopic scattering of cracks initiated at single impurity atoms.
AB  - Brittle crystals, such as coloured gems, have long been known to cleave with
      atomically smooth fracture surfaces, despite being impurity laden, suggesting
      that isolated atomic impurities do not generally cause cracks to deflect. Whether
      cracks can ever deviate when hitting an atomic defect, and if so how they can go
      straight in real brittle crystals, which always contain many such defects, is
      still an open question. Here we carry out multiscale molecular dynamics
      simulations and high-resolution experiments on boron-doped silicon, revealing
      that cracks can be deflected by individual boron atoms. The process, however,
      requires a characteristic minimum time, which must be less than the time spent by
      the crack front at the impurity site. Deflection therefore occurs at low crack
      speeds, leading to surface ridges which intensify when the boron-dopage level is
      increased, whereas fast-moving cracks are dynamically steered away from being
      deflected, yielding smooth cleavage surfaces. 

PMID- 24026346
TI  - The size of a melanin-based plumage ornament correlates with glucocorticoid
      receptor concentrations in the skin of that ornament.
AB  - Glucocorticoid hormones such as corticosterone (CORT) play crucial roles in many
      physiological processes. CORT's actions are primarily mediated via binding to two
      receptors (glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs))
      in different target tissues. CORT receptors can be independently regulated from
      circulating hormone titres, from tissue to tissue and even within different
      regions of the same tissue type. Increasing evidence has shown relationships
      between circulating CORT and melanin-based pigmentation in skin and feathers, yet
      to our knowledge, there have been no studies of CORT receptors in the skin of
      melanized ornaments. Male house sparrows (Passer domesticus) have a black,
      melanized bib, and evidence suggests that bib size is an important intraspecific
      signal. We examined the relationship between bib area and tissue sensitivity to
      CORT by quantifying GR and MR in bib skin and in adjacent paler-feathered belly
      skin (as a control tissue) at different life-history stages using radioligand
      binding assays. Males with larger bibs relative to their life-history stage had
      less GR in bib skin, but not belly skin, than males with smaller bibs. These
      results suggest a connection between the size of a melanin-based ornament and the
      underlying tissue's responsiveness to CORT. 

PMID- 24026347
TI  - Wild Asian elephants distinguish aggressive tiger and leopard growls according to
      perceived danger.
AB  - Prey species exhibit antipredator behaviours such as alertness, aggression and
      flight, among others, in response to predators. The nature of this response is
      variable, with animals reacting more strongly in situations of increased
      vulnerability. Our research described here is the first formal study to
      investigate night-time antipredator behaviour in any species of elephants, Asian
      or African. We examined the provocative effects of elephant-triggered tiger and
      leopard growls while elephants attempted to crop-raid. Tigers opportunistically
      prey on elephant calves, whereas leopards pose no threat; therefore, we predicted
      that the elephant response would be reflective of this difference. Elephants
      reacted similarly cautiously to the simulated presence of felids of both species
      by eventually moving away, but differed markedly in their more immediate
      behavioural responses. Elephants retreated silently to tiger-growl playbacks,
      whereas they responded with aggressive vocalizations, such as trumpets and
      grunts, to leopard-growl playbacks. Elephants also lingered in the area and
      displayed alert or investigative behaviours in response to leopard growls when
      compared with tiger growls. We anticipate that the methods outlined here will
      promote further study of elephant antipredator behaviour in a naturalistic
      context, with applications for conservation efforts as well. 

PMID- 24026348
TI  - Reassessing the association between facial structure and baseball performance: a
      comment on Tsujimura & Banissy (2013).

PMID- 24026349
TI  - Covariance of paternity and sex with laying order explains male bias in extra
      pair offspring in a wild bird population.
AB  - It has been hypothesized that parents increase their fitness by biasing the sex
      ratio of extra-pair offspring (EPO) towards males. Here, we report a male bias
      among EPO in a wild population of blue tits (Cyanistes caeruleus). This resulted
      from a decline in both the proportion of males and EPO over the laying order of
      eggs in the clutch. However, previous studies suggest that, unlike the decline in
      EPO with laying order, the relationship between offspring sex ratio and laying
      order is not consistent between years and populations in this species. Hence, we
      caution against treating the decline in proportion of males with laying order,
      and the resulting male bias among EPO, as support for the above hypothesis.
      Variable patterns of offspring sex and paternity over the laying order may
      explain inconsistent associations between offspring sex and paternity, between
      and within species. 

PMID- 24026350
TI  - An intestinal arsonist: pathobiont ignites IBD and flees the scene.

PMID- 24026352
TI  - Modest alcohol consumption decreases the risk of non-alcoholic fatty liver
      disease: a meta-analysis of 43 175 individuals.

PMID- 24026351
TI  - Genetic inactivation of Nupr1 acts as a dominant suppressor event in a two-hit
      model of pancreatic carcinogenesis.
AB  - BACKGROUND: Nuclear protein 1 (Nupr1) is a major factor in the cell stress
      response required for Kras(G12D)-driven formation of pancreatic intraepithelial
      neoplastic lesions (PanINs). We evaluated the relevance of Nupr1 in the
      development of pancreatic cancer. METHODS: We investigated the role of Nupr1 in
      pancreatic ductal adenocarcinoma (PDAC) progression beyond PanINs in Pdx1-cre;LSL
      Kras(G12D);Ink4a/Arf(fl/fl)(KIC) mice. RESULTS: Even in the context of the second
      tumorigenic hit of Ink4a/Arf deletion, Nupr1 deficiency led to suppression of
      malignant transformation involving caspase 3 activation in premalignant cells of
      KIC pancreas. Only half of Nupr1-deficient;KIC mice achieved PDAC development,
      and incident cases survived longer than Nupr1(wt);KIC mice. This was associated
      with the development of well-differentiated PDACs in Nupr1-deficient;KIC mice,
      which displayed enrichment of genes characteristic of the recently identified
      human classical PDAC subtype. Nupr1-deficient;KIC PDACs also shared with human
      classical PDACs the overexpression of the Kras-activation gene signature. In
      contrast, Nupr1(wt);KIC mice developed invasive PDACs with enriched gene
      signature of human quasi-mesenchymal (QM) PDACs. Cells derived from Nupr1
      deficient;KIC PDACs growth in an anchorage-independent manner in vitro had higher
      aldehyde dehydrogenase activity and overexpressed nanog, Oct-4 and Sox2
      transcripts compared with Nupr1(wt);KIC cells. Moreover, Nupr1-deficient and
      Nurpr1(wt);KIC cells differed in their sensitivity to the nucleoside analogues
      Ly101-4b and WJQ63. Together, these findings show the pivotal role of Nupr1 in
      both the initiation and late stages of PDAC in vivo, with a potential impact on
      PDAC cell stemness. CONCLUSIONS: According to Nupr1 status, KIC mice develop
      tumours that phenocopy human classical or QM-PDAC, respectively, and present
      differential drug sensitivity, thus becoming attractive models for preclinical
      drug trials.

PMID- 24026353
TI  - Resource reallocation does not influence estimates of pollen limitation or
      reproductive assurance in Clarkia xantiana subsp. parviflora (Onagraceae).
AB  - PREMISE OF STUDY: Studies of pollen limitation and the reproductive assurance
      value of selfing are important for examining the process of floral and mating
      system evolution in flowering plants. Recent meta-analyses have shown that common
      methods for measuring pollen limitation may often lead to biased estimates.
      Specifically, experiments involving single- or few-flower manipulations per plant
      tend to overestimate pollen limitation compared to those involving manipulations
      on most or all flowers per plant. Little previous work has explicitly tested for
      reallocation within individual systems using alternative methods and response
      variables. * METHODS: We performed single-flower and whole-plant pollen
      supplementation and emasculation of flowers of Clarkia xantiana subsp. parviflora
      to estimate pollen limitation (PL) and reproductive assurance (RA). We compared
      levels of PL and RA using the following response variables: fruit set,
      seeds/flower, and seeds/plant. We also assessed the germination and viability of
      seeds to evaluate potential variation in pollen quality among treatments. * KEY
      RESULTS: Autonomous selfing in Clarkia xantiana subsp. parviflora eliminates
      pollen limitation and provides reproductive assurance. Estimates from single
      flower manipulations were not biased, closely resembling those from whole-plant
      manipulations. All three response variables followed the same pattern, but
      treatments were only significantly different for seeds/flower. Pollen quality, as
      indicated by seed viability, did not differ among treatments. * CONCLUSIONS:
      Partial plant manipulations provided reliable estimates of pollen limitation and
      reproductive assurance. These estimates were also unaffected by accounting for
      pollen quality. Although whole plant manipulations are desirable, this experiment
      demonstrates that in some systems partial plant manipulations can be used in
      studies where whole-plant manipulations are not feasible.

PMID- 24026354
TI  - Identification and symbiotic ability of Psathyrellaceae fungi isolated from a
      photosynthetic orchid, Cremastra appendiculata (Orchidaceae).
AB  - PREMISE OF THE STUDY: Photosynthetic orchids found in highly shaded forests are
      often mixotrophic, receiving part of their carbon energy via ectomycorrhizal
      fungi that had originally received carbohydrate from trees. A photosynthetic
      orchid, Cremastra appendiculata, is also found under highly shaded forest, but
      our preliminary data suggested that its associated fungi were not
      ectomycorrhizal. We tested whether their relation is an unusual example of a
      mixotrophic orchid associating with saprotrophic fungi by direct detection of
      fungal DNAs in conjunction with isolation of the fungus in pure culture and
      experimental inoculation of orchid seeds with the fungus. * METHODS: For isolated
      mycobionts of C. appendiculata plants, two regions of nuclear ribosomal DNA, the
      internal transcribed spacer (ITS) and the large subunit (LSU), were sequenced,
      and fruiting bodies of the one isolate, SI1-1 were induced. In addition, two
      fungal isolates, SI1-1 and KI1-1, were grown in symbiotic cultures with C.
      appendiculata to verify their status as mycobionts. * KEY RESULTS: In
      phylogenetic analyses, all isolates clustered with fungi belonging to Coprinellus
      in Psathyrellaceae of Agaricales. Phylogenetic analyses of these DNA sequences
      showed that five fungal isolates from C. appendiculata, including SI1-1 and two
      mycobionts isolated from the mycoheterotrophic orchid Epipogium roseum, have very
      similar ITS sequences. Isolate SI1-1 was identified as Coprinellus domesticus
      based on the morphological characteristics of the fruiting body. Isolates SI1-1
      and KI1-1 induced seed germination of C. appendiculata as mycobionts. *
      CONCLUSIONS: This report is the first of a mycorrhizal symbiosis between a fungus
      in Psathyrellaceae and a photosynthetic orchid, revealing a new pathway to full
      mycoheterotrophy and contributing to our understanding of the evolution of
      mycoheterotrophy.

PMID- 24026355
TI  - Economic stress and lack of internal health locus of control: a life course
      approach.
AB  - AIMS: To investigate associations between economic stress in childhood and
      adulthood, and lack of internal health locus of control (HLC), testing the
      accumulation and critical period life course hypotheses. METHODS: A cross
      sectional public health (postal) survey was conducted in Skane in 2008, based on
      a random sample with 28,198 participants in the age interval 18-80 years, with
      55% participation. Logistic regressions analyzed associations between childhood
      and current economic stress, and lack of internal HLC. RESULTS: A 33.7%
      prevalence of men and 31.8% of women lack internal HLC, which was significantly
      associated with the covariates included. The accumulation hypothesis was partly
      supported because combined childhood and adulthood economic stress exposures were
      significantly associated with lack of internal HLC in a graded manner. The
      critical period hypothesis was not supported since the association between
      economic stress in childhood and lack of internal HLC was partly significant in
      the final model, and the association with adult (current) economic stress was
      also significant. CONCLUSIONS: The accumulation hypothesis was partly supported.
      The critical period hypothesis was not supported since both childhood and current
      economic stress experience were significantly associated with lack of internal
      HLC. Economic conditions in childhood as well as adulthood are plausibly of
      relevance for HLC.

PMID- 24026356
TI  - Associations of parental influence and 10-11-year-old children's physical
      activity: are they mediated by children's perceived competence and attraction to
      physical activity?
AB  - AIMS: This cross-sectional study had two aims: firstly, to study the associations
      of parental influence in the form of encouragement, father and mother modelling
      and involvement on children's physical activity (PA), and secondly, to study the
      mediation effect of encouragement, father and mother modelling and involvement on
      children's PA through children's perceived competence and attraction to PA.
      METHODS: A total of 1278 children (response rate 79%), aged 10-11 years,
      participated in the study in the autumn of 2006. Of these children, 883 children
      completed all the data in a questionnaire assessing their self-reported PA,
      perceived competence, attraction to PA, and perceived parental influence. The
      associations were examined by multiple mediator analyses with bootstrapping
      method. All the models were adjusted with gender and grade. RESULTS: The analyses
      pointed out that father modelling had a direct effect on children's physical
      activity, whereas encouragement, mother modelling, and involvement had an
      indirect effect through perceived competence and attraction to physical activity
      on children's physical activity. The strongest indirect association was formed
      from encouragement through attraction to physical activity to children's physical
      activity. CONCLUSIONS: The results show that parents influence on children's
      physical activity in a variety of ways. Parents influence their children's
      physical activity in direct and indirect manners through their encouragement,
      involvement and modelling. Furthermore, mother and father influence their
      children's physical activity in different ways. This versatility should be taken
      into consideration in future interventions.

PMID- 24026357
TI  - 'A post-transplant person': Narratives of heart or lung transplantation and
      intensive care unit delirium.
AB  - Exploring patients' narratives can lead to new understandings about perceived
      illness states. Intensive Care Unit delirium is when people experience transitory
      hallucinations, delusions or paranoia in the Intensive Care Unit and little is
      known about how this experience affects individuals who have had a heart or lung
      transplant. A total of 11 participants were recruited from two heart and lung
      transplant services and were invited to tell their story of transplant and
      Intensive Care Unit delirium. A narrative analysis was conducted and the findings
      were presented as a shared story. This shared story begins with death becoming
      prominent before the transplant: 'you live all the time with Mr Death on your
      shoulder'. Following the operation, death permeates all aspects of dream worlds,
      as dreams in intensive care 'tunes into the subconscious of your fears'. The next
      part of the shared story offers hope of restitution; however, this does not last
      as reality creeps in: 'I thought it was going to be like a miracle cure'.
      Finally, the restitution narrative is found to be insufficient and individuals
      differ in the extent to which they can achieve resolution. The societal discourse
      of a transplant being a 'gift', which gives life, leads to internalised
      responsibility for the 'success' or 'failure' of the transplant. Participants
      describe how their experiences impact their sense of self: 'a post-transplant
      person'. The clinical implications of these findings are discussed. 

PMID- 24026358
TI  - 'It seemed churlish not to': How living non-directed kidney donors construct
      their altruism.
AB  - Our objective was to explore how prospective altruistic kidney donors construct
      their decision to donate. Using a qualitative design and biographical-narrative
      semi-structured interviews, we aimed to produce text for analysis on two levels:
      the social implications for subjectivity and practice and a tentative
      psychodynamic explanation of the participants' psychological investment in the
      discourses they used. A total of six prospective altruistic kidney donors were
      interviewed. A psychosocial approach to the analysis was taken. In-depth
      discourse analysis integrated Foucauldian with psycho-discursive approaches and
      psychodynamic theory was applied to sections of text in which participants seemed
      to have particular emotional investment. Analysis generated three major
      discursive themes: other-oriented, rational and self-oriented discourses. The
      desire to donate was experienced as compelling by participants. Participants used
      discourses to position themselves as concerned with the needs of the recipient,
      to resist questioning and criticism, and to manage difficult feelings around
      mortality. Participants tended to reject personal motivations for altruistic
      donation, positioning relatives' disapproval as selfish and illogical. These
      results suggest that the term 'altruistic' for living non-directed organ donation
      constrains available discourses, severely limiting what can be said, felt,
      thought and done by donors, clinicians and the public. A more useful approach
      would acknowledge potential psychological motives and gains for the donor. 

PMID- 24026359
TI  - 'There's a lot of tasks that can be done by any': Findings from an ethnographic
      study into work and organisation in UK community crisis resolution and home
      treatment services.
AB  - Across the United Kingdom, large numbers of crisis resolution and home treatment
      services have been established with the aim of providing intensive, short-term
      care to people who would otherwise be admitted to mental health hospital. Despite
      their widespread appearance, little is known about how crisis resolution and home
      treatment services are organised or how crisis work is done. This article arises
      from a larger ethnographic study (in which 34 interviews were conducted with
      practitioners, managers and service users) designed to generate data in these and
      related areas. Underpinned by systems thinking and sociological theories of the
      division of labour, the article examines the workplace contributions of mental
      health professionals and support staff. In a fast-moving environment, the work
      which was done, how and by whom, reflected wider professional jurisdictions and a
      recognisable patterning by organisational forces. System characteristics
      including variable shift-by-shift team composition and requirements to undertake
      assessments of new referrals while simultaneously providing home treatment shaped
      the work of some, but not all, professionals. Implications of these findings for
      larger systems of work are considered. 

PMID- 24026360
TI  - Differences in treatment of Spitz nevi and atypical Spitz tumors in pediatric
      patients among dermatologists and plastic surgeons.

PMID- 24026361
TI  - The evaluation and treatment of prostate-related LUTS in the primary care
      setting: the next STEP.
AB  - The primary care provider is in an optimal position to identify and care for the
      patient affected by prostate-related lower urinary tract symptoms (BPH-LUTS).
      This assessment can be readily accomplished with a good history and only a few
      simple, in-office tests. In some instances, the primary care provider may believe
      that they do not have the experience, comfort level or time to perform an
      adequate evaluation of the problem. Therefore, in this article, we describe the
      function of the lower urinary tract, as well as the rationale behind the medical
      history, examination and tests needed in order to diagnose and treat, or refer,
      the patient presenting with BPH-LUTS. We will also update the literature-based
      STEP (simplified treatment of the enlarged prostate) approach, which was
      initially published in 2009, to include recently described therapeutic options. 

PMID- 24026362
TI  - Role of complimentary therapy for male LUTS.
AB  - Phytotherapy, the use of plant based extracts (derived from fruits, seeds, roots,
      or bark) as medicines or health-promoting agents are often used as first-line
      treatments for bothersome male lower urinary tract symptoms (LUTS). Their use,
      either as monotherapy or in conjunction with conventional pharmaceutical
      treatments is becoming increasingly popular worldwide. There are now over 30 of
      these phytotherapeutic compounds available, with saw palmetto and pygeum being
      the most widely used. This paper discusses the mechanism of action, reported
      efficacies and potential side effects of a number of the most common
      phytotherapies being used for male LUTS, as well as summarizes outcome data
      relevant to these agents from the most current peer-reviewed publications. 

PMID- 24026364
TI  - Strengthening psychiatry's numbers.

PMID- 24026366
TI  - Preparing psychiatrists for leadership roles in healthcare.

PMID- 24026363
TI  - The ClC-3 chloride channel associated with microtubules is a target of paclitaxel
      in its induced-apoptosis.
AB  - Recent evidences show that cationic fluxes play a pivotal role in cell apoptosis.
      In this study, the roles of Cl(-) channels in paclitaxel-induced apoptosis were
      investigated in nasopharyngeal carcinoma CNE-2Z cells. Chloride current and
      apoptosis were induced by paclitaxel and inhibited by chloride channel blockers.
      Paclitaxel-activated current possessed similar properties to volume-activated
      chloride current. After ClC-3 was knocked-down by ClC-3-siRNA, hypotonicity
      activated and paclitaxel-induced chloride currents were obviously decreased,
      indicating that the chloride channel involved in paclitaxel-induced apoptosis may
      be ClC-3. In early apoptotic cells, ClC-3 was up-regulated significantly; over
      expressed ClC-3 was accumulated in cell membrane to form intercrossed filaments,
      which were co-localized with alpha-tubulins; changes of ultrastructures and
      decrease of flexibility in cell membrane were detected by atomic force
      microscopy. These suggest that ClC-3 is a critical target of paclitaxel and the
      involvement of ClC-3 in apoptosis may be associated with its accumulation with
      membrane microtubules and its over activation. 

PMID- 24026367
TI  - Child welfare training in child psychiatry residency: a program director survey.
AB  - OBJECTIVE: This study surveys child psychiatry residency program directors in
      order to 1) characterize child welfare training experiences for child psychiatry
      residents; 2) evaluate factors associated with the likelihood of program
      directors' endorsing the adequacy of their child welfare training; and 3) assess
      program directors' familiarity with some existing child welfare training and
      information resources. METHOD: Program directors of American College of Graduate
      Medical Education (ACGME)-accredited child psychiatry residency programs were
      surveyed anonymously. Participants characterized their program's child welfare
      training curriculum and indicated their awareness of selected child welfare
      information and training resources. RESULTS: In all, 68% of program directors
      responded; 90% of respondents indicated that their residents encounter child
      welfare-involved youth very frequently or frequently. Just over half of the
      respondents reported inadequate training materials, and half were aware of at
      least one of the three queried child welfare information resources. However,
      nearly 40% of respondents who were familiar with the queried child welfare
      resources still reported having inadequate training materials. Respondents with
      adequate training materials were more likely to classify their program as
      devoting enough time to child welfare training. Respondents at sites that spent
      less than 5 hours on non-didactic child welfare training during residency were
      more likely to indicate that not enough time was spent on training. CONCLUSION:
      The findings of this study suggest that increasing child psychiatry program
      director awareness of existing child welfare information resources and providing
      6-or-more hours of non-didactic child welfare training, two feasible and
      relatively low resource actions, may improve child welfare training in child
      psychiatry residencies.

PMID- 24026368
TI  - Residents as teachers: psychiatry and family medicine residents' self-assessment
      of teaching knowledge, skills, and attitudes.
AB  - OBJECTIVE: Residents are one of the prime sources of information and education
      for medical students. As an initial step in supporting residents as teachers, a
      baseline self-assessment of residents' knowledge, skills, attitudes, and values
      related to teaching was conducted among psychiatry and family medicine residents
      to compare and improve their confidence and skills as teachers. METHOD:
      Psychiatry residents (N=12) and family medicine residents (N=23) completed self
      assessments of their knowledge, skills, attitudes, and values related to
      teaching. Residents also were asked to list steps used in the One-Minute
      Preceptor process and estimate the time each spent in teaching. Descriptive
      summary statistics were used for four main areas related to teaching; t-test and
      chi-square analyses were conducted to ascertain whether there was a significant
      difference in resident groups. RESULTS: In the current study, the perceived
      amount of time spent for teaching patients was significantly higher among family
      practice residents, whereas no group differences were found for time teaching
      medical students, peers, community members, non-physicians, or others. However,
      family medicine residents rated themselves higher than psychiatry residents in
      their understanding of their roles in teaching medical students and teaching
      patients. Also, family medicine residents' self-reported teaching skills were
      more advanced (82.4%) than psychiatry residents' (54.2%). They most likely
      applied at least two different teaching methods in inpatient and outpatient
      settings, as compared with psychiatry residents. No significant group differences
      were found in the other 15 items assessing teaching knowledge, skills, attitudes,
      and values. CONCLUSION: Results indicate that residents' knowledge, skills,
      attitudes, and values regarding teaching varies across institutions and training
      programs. The psychiatry residents in this study do not clearly understand their
      role as educators with patients and medical students; they have a less clear
      understanding of teaching techniques, and report spending less time educating
      patients than do family medicine residents. The differences might be due to
      different patient populations and treatment settings. The study suggests that
      psychiatry residents may have difficulty adapting the One-Minute Preceptor
      technique in psychiatric settings. Results serve as a benchmarking study in a
      performance-improvement program to enhance psychiatry residents' teaching skills.

PMID- 24026369
TI  - A curriculum in measurement-based care: screening and monitoring of depression in
      a psychiatric resident clinic.
AB  - OBJECTIVE: The goal of this curriculum was to train residents in measurement
      based care (MBC). METHOD: Third-year psychiatry residents were educated in MBC
      through didactic seminars and a quality-improvement (QI) initiative with the goal
      of implementing the Patient Health Questionnaire Depression Scale (PHQ-9) to
      screen and monitor patients for symptoms of depression. RESULTS: Residents
      suggested strategies for integrating the PHQ-9 into the clinic. Over the first 6
      months, residents showed an increase in rate of depression screening from 4% to
      92% of patients. Also, they increased monthly monitoring of outpatients with a
      diagnosis of depression from 1% to 76%. Residents who used the PHQ-9 to monitor
      patients with depression were significantly more likely to use additional
      standardized assessments. CONCLUSIONS: Combining an educational intervention with
      QI strategies can significantly affect residents' use of standardized assessments
      in an outpatient setting. Using standardized measures allows residents to assess
      their own clinical effectiveness, an emerging priority in training.

PMID- 24026370
TI  - Does early mentorship in child and adolescent psychiatry make a difference? The
      Klingenstein Third-Generation Foundation Medical Student Fellowship Program.
AB  - OBJECTIVE: There is a critical shortage of child and adolescent psychiatrists in
      the United States. Increased exposure, through mentorship, clinical experiences,
      and research opportunities, may increase the number of medical students selecting
      child and adolescent psychiatry (CAP) as a career choice. METHOD: Between 2008
      and 2011, 241 first-year participants of a program to increase exposure to CAP,
      funded by the Klingenstein Third-Generation Foundation (KTGF) at 10 medical
      schools completed baseline surveys assessing their opinions of and experiences in
      CAP, and 115 second-year participants completed follow-up surveys to reflect 1
      year of experience in the KTGF Program. RESULTS: Students reported significantly
      increased positive perception of mentorship for career and research guidance,
      along with perceived increased knowledge and understanding of CAP. CONCLUSIONS:
      Results suggest that the KTGF Program positively influenced participating medical
      students, although future studies are needed to determine whether these changes
      will translate into more medical students entering the field of CAP.

PMID- 24026371
TI  - Knowledge of psychotropics and prescribing preferences of family physicians: a
      preliminary study.
AB  - OBJECTIVE: Family doctors often provide care for their patients' mental health
      needs. This study was designed to survey their opinions and actual practice of
      providing mental health care, specifically, prescribing psychotropic medication
      to outpatients with mild/moderate mental health disorders. METHOD: A group of 241
      family medicine faculty and residents completed a self-administered survey
      designed to evaluate their comfort level with providing brief office counseling
      and psychotropic medication to their patients with mental health disorders.
      RESULTS: The majority of the sample reported that they prescribe psychotropic
      medication to their patients, despite often assessing their knowledge of
      psychotropics as absent or marginal. Most of the sample expressed strong interest
      in learning more about prescribing psychiatric medications. CONCLUSION: Results
      of the study suggest the need for improved training of family physicians who
      often prescribe psychiatric medications for outpatients with mental health
      disorders.

PMID- 24026373
TI  - Comparing treatment outcomes of bipolar patients between psychiatry residents and
      attending physicians.
AB  - OBJECTIVE: The authors sought to compare the outcomes of patients treated by
      psychiatric residents and attending psychiatrists. METHOD: Charts of 121
      outpatients meeting criteria for bipolar spectrum disorder were analyzed.
      Residents treated 41, and attending physicians 80, of 121 patients. Improvement
      was defined as at least 12 consecutive months of the following: Remission-
      euthymic mood; Response--much improved mood, not meeting DSM-IV criteria for mild
      illness; Relapse--remission or response followed by recurrence. The Active
      Illness group contained patients who did not have 12 months of Remission or
      Response. RESULTS: The percentage of improved patients was similar between
      residents (46.3%; 19/41) and attending physicians (42.5%; 34/80). There was a
      significant difference in the number of patients in the Remission or Response
      categories between attending physicians: (26.5%; 21/80) and residents (12.2%;
      5/41). CONCLUSION: Similar numbers of residents' and attending physicians'
      patients achieved improvement for 12 months, but twice the number of attending
      physicians' patients achieved and maintained euthymia.

PMID- 24026374
TI  - A psychopharmacology course for psychiatry residents utilizing active-learning
      and residents-as-teachers to develop life-long learning skills.
AB  - OBJECTIVE: The authors describe the implementation and evaluation of a 1-year
      psychopharmacology course using residents-as-teachers and active-learning
      exercises intended to improve understanding of current psychopharmacology and its
      evidence base, and skills for life-long learning. METHOD: Weekly classes were
      devoted to psychotropic medications, treating specific disorders, and use of
      psychotropics in special patient populations. Each class was divided into three
      sections: a pharmacology review, a literature review and a faculty-led discussion
      of clinical questions. Each class included residents as teachers, an audience
      response system and questions for self-assessment. Resident and faculty
      presenters evaluated the course weekly and all residents were given a year-end
      evaluation RESULTS: Resident and faculty evaluations indicated an overall
      positive response. The residents reported improved perception of knowledge and
      engagement with this interactive format. CONCLUSION: The course was well
      received, demonstrating the viability and value of residents taking a more active
      role in their own learning.

PMID- 24026375
TI  - Lost in documentation: a study of case-formulation documentation in letters after
      outpatient assessment.
AB  - OBJECTIVE: The authors sought to find out how frequently case-formulation is
      documented by psychiatrists after initial assessment in an outpatient clinic.
      METHOD: Assessment letters for 150 new referrals/new referrals to a psychiatric
      clinic in Rotherham, U.K. were examined for the presence or absence of a case
      formulation, as well as the different sections of the psychiatric history.
      RESULTS: A group of 150 assessment letters were selected and examined. An
      overwhelming majority (94%) of letters did not include any case-formulation; this
      finding was not affected by the grade of the doctor. CONCLUSIONS: Although case
      formulation is considered an important skill by various training bodies, it seems
      that this is rarely translated into daily clinical practice. The authors discuss
      the possible reasons for this deficiency and discuss potential solutions.

PMID- 24026376
TI  - Emotional intelligence and psychiatry residents: does the PRITE measure emotional
      intelligence?
AB  - OBJECTIVE: The authors assessed the relationship between Emotional Intelligence
      (EI) and Psychiatry Resident In-Training Exam (PRITE) scores. EI is important to
      the therapeutic alliance. The hypothesis tested was that PRITE scores would
      correlate with EI. METHOD: Adult Psychiatry residents participated. The PRITE was
      administered, and participants completed the online Bar-On Emotional Intelligence
      Quotient questionnaire. RESULTS: Pearson correlation coefficients were calculated
      for PRITE score and overall EI score, and with the 15 EI subscales. The
      correlation for PRITE and overall EI was not significant. Three EI subscales had
      statistically significant correlations with PRITE score: empathy, social
      responsibility, and impulse control. CONCLUSIONS: There was no significant
      correlation between overall EI and PRITE scores. There was an inverse
      relationship between PRITE scores and empathy, social responsibility, and impulse
      control. The authors discuss possible explanations for these relationships.

PMID- 24026377
TI  - Improving residents' performance on the PRITE: is there a role for peer-assisted
      learning?
AB  - OBJECTIVE: The authors implemented a peer-assisted learning approach to prepare
      residents for the Psychiatry Resident-In-Training Examination (PRITE), with the
      goal of increasing test performance. METHOD: The authors developed a PRITE review
      curriculum utilizing a peer-assisted learning approach. The residents were
      randomly assigned to teams and instructed to teach assigned topic(s). The
      participants' PRITE scores before and after the intervention were compared with
      the PRITE scores of the previous residents. RESULTS: PGY-2 residents achieved the
      highest psychiatry percentile increase, and PGY-3 residents achieved the highest
      psychiatry percentile in the past 7 years. PGY-4 residents' psychiatry percentile
      decreased, although two residents from the previous year left for a fellowship,
      and the program accepted one PGY-4 transfer. All of the groups' neurology
      percentile increased, but were not substantially different from the previous
      years. CONCLUSION: Our preliminary study has shown that implementing a peer
      learning strategy to prepare residents for the PRITE is feasible and may lead to
      promising results.

PMID- 24026378
TI  - From Hannibal Lecter to Alex Cross: forensic mental health experts in popular
      fiction.

PMID- 24026380
TI  - Group Day: experiential learning about group psychotherapy for psychiatry
      residents at University of Toronto.

PMID- 24026381
TI  - Spanning distance and culture in psychiatric education: a teleconferencing
      collaboration between Cambodia and the United States.

PMID- 24026382
TI  - Psychiatry residents' attitudes toward spirituality in psychiatry.

PMID- 24026383
TI  - Is doing "a good job, for a psychiatry resident" good enough?

PMID- 24026384
TI  - On-call reform: blessing or bane? Psychiatry residents' perspectives.

PMID- 24026385
TI  - A perspective: from the policy world to the clinical world.

PMID- 24026386
TI  - APOE polymorphism and diabetic nephropathy.
AB  - Epidemiological studies suggest the existence of a genetic susceptibility to the
      development of diabetic nephropathy. The apolipoprotein E gene (APOE), which is
      well known to have a polymorphism (epsilon2, epsilon3, and epsilon4) in exon 4,
      has been considered a candidate gene susceptible to this complication, because
      this variation was reportedly involved in lipid metabolism. To date, numerous
      case-control studies in patients with type 1 and type 2 diabetes have been
      reported. Although the epsilon2 allele of the APOE polymorphism tends to be
      associated with an increased risk for diabetic nephropathy, the results of these
      case-control comparisons are conflicting. However, a family-based study (the
      transmission/disequilibrium test) provided strong evidence that the epsilon2
      allele was preferentially transmitted to patients with diabetic nephropathy but
      not transmitted to those without it. Several prospective follow-up studies also
      reported an increased risk for progression to higher stages of diabetic
      nephropathy for the epsilon2 carriers. Furthermore, two recent meta-analyses
      reported that the epsilon2 allele is associated with a risk for diabetic
      nephropathy. Based on the results of these studies, the epsilon2 allele of the
      APOE polymorphism seems to be a genetic risk factor for diabetic nephropathy
      susceptibility. However, this genetic effect only accounts for a small proportion
      of this complication, and the mechanism remains unclear at present. Further
      studies are needed to explore whether genotyping of the APOE polymorphism in
      patients with diabetes is of value for better management in clinical practice. 

PMID- 24026387
TI  - In vitro comparative assessment of different viability assays in Acanthamoeba
      castellanii and Acanthamoeba polyphaga trophozoites.
AB  - The species of the genus Acanthamoeba are opportunistic protozoan parasites that
      cause different diseases in humans, such as amoebic keratitis and granulomatous
      encephalitis. The rise in the rate of Acanthamoeba keratitis, mainly due to the
      increase in contact lens wearers, turns the development of viability assays using
      a multi-well plate reader as a tool for screening new antiamoebic agents in vitro
      into an important goal. In our study, the viability assays PrestoBlue(r),
      resazurin sodium salt, 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium
      bromide (MTT) and CellTiter96(r) were tested for their suitability as time-saving
      alternatives to the classical manual or direct-counting method, assessing the
      effect of the antiamoebic agent chlorhexidine digluconate and temperature on
      Acanthamoeba castellanii (ATCC(r) 30234TM) and Acanthamoeba polyphaga 2961.
      Although resazurin and MTT have already been previously used in amoeba viability
      assays to test the activities of antiamoebic agents in vitro, it is the first
      time that PrestoBlue(r) and CellTiter96(r) are used for this purpose. Results
      indicated that the viability assays were strain-dependent leading in some cases
      to an overestimation of the real situation of viable cells. This implies that
      each viability assay ought to be set up for each amoeba strain studied. 

PMID- 24026388
TI  - Analysis of differentially expressed genes of Trichinella spiralis larvae
      activated by bile and cultured with intestinal epithelial cells using real-time
      PCR.
AB  - The activation of Trichinella spiralis muscle larvae (ML) by exposure to
      intestinal contents or bile and the intestinal epithelial cells (IECs) themselves
      are two pivotal requirements for the in vitro larval invasion of IECs. However,
      it is yet unknown which genes are involved in the process of larval invasion. The
      purpose of the present study was to analyze the differentially expressed genes of
      T. spiralis larvae activated by bile and cultured with IECs by using real-time
      polymerase chain reaction. Ten T. spiralis genes encoded the proteins produced by
      the larvae after co-culture with IECs were selected. Compared with untreated ML,
      four genes were up-regulated in both bile-activated and cell-cultured larvae,
      including calcium-dependent secretion activator (Csa; 2.55- and 16.04-fold,
      respectively), multi cystatin-like domain protein precursor (Mcd; 4.36 and 52),
      serine protease (Sp; 2.03 and 20.02), and intermediate filament protein ifa-1
      (Ifa 1; 2 and 3.31). The expression of two genes, enolase (Eno; 1.51) and
      ribosomal protein S6 kinase beta-1 (Rsk; 1.49), was up-regulated only in cell
      cultured larvae, not in bile-activated larvae. The expression of secreted 5'
      nucleotidase (5 N; 1.42) and putative serine protease (Psp; 1.41) was up
      regulated in bile-activated larvae, but was not changed or down-regulated after
      cultured with IECs. ATP synthase F1, beta subunit (ATPase; 0.58 and 0.51) and
      serine protease precursor (Spp; 0.42 and 0.65) were down-regulated in both bile
      activated and cell-cultured larvae. This study provide some differentially
      expressed genes among the untreated (normal), bile-activated and cell-cultured
      larvae of T. spiralis. The up-regulated genes might be related with the larval
      invasion of IECs, but their exact biological functions need to be further
      investigated. This study will be helpful to further elucidate the molecular
      mechanism of the invasion of IECs by T. spiralis larvae and to better understand
      the interaction between parasite and host enterocytes. 

PMID- 24026389
TI  - The Postpartum Worry Scale-Revised: an initial validation of a measure of
      postpartum worry.
AB  - Postpartum anxiety is a condition of concern due to associated difficulties for
      the mother, her relationships, and her infant's development. We revised one
      measure of postpartum anxiety symptoms, the Postpartum Worry Scale (PWS) to
      include items that tap concerns related to infant health and development,
      important potential domains of postpartum worry. This study presents the initial
      phase of validation for the PWS-R. An online sample of 1,231 mothers of infants
      ages birth to 24 months completed the PWS-R as well as a battery of measures. We
      conducted a split-sample confirmatory factor analysis (CFA) to assess the latent
      factor structure, and a series of models were tested to refine the measure. The
      newly constructed factors were correlated with theoretically similar measures to
      test the construct validity. Initial model testing revealed a four-factor
      structure (i.e., Relationships, Household, Time Allocations, and Health and
      Development) that included 13 items. Two-group CFA confirmed the latent factor
      structure. Theoretically similar measures correlated moderately with the newly
      created PWS-R factors. The psychometric findings for the PWS-R provide
      preliminary support for its use as a measure of postpartum worry. Next steps in
      the iterative validation process are considered. Recommendations for the PWS-R's
      use in clinical and research contexts are discussed. 

PMID- 24026390
TI  - Mandibular lingual canals distribute to the dental crypts in prenatal stage.
AB  - PURPOSE: To describe configurations of human prenatal mandibular, lingual canals
      using a limited-field cone beam computed tomography (CBCT) to examine their
      origin and anatomical significance. MATERIALS AND METHODS: Nine fetal mandibles
      were examined using a CBCT. Mandibular maturity was assessed according to the
      mandibular size measured directly and image findings on development of dental
      crypts. Mandibular, lingual canals and the related foramina (mandibular, mental,
      and lingual foramina) were observed on axial, sagittal, and cross-sectional
      images. The horizontal position of mental and lingual foramina was assessed by
      direct observation using a loupe. RESULTS: In all nine mandibles, CBCT images
      depicted three separate mandibular canals, which individually occurred at the
      ramus area. One was a short canal directly connecting to the permanent molar
      crypt. The other two showed a parallel course, following the mandibular corpus
      toward the frontal area; the upper one connected to the mental foramen, and the
      lower one distributed anterior area of canine and incisor crypts. Lingual
      foramina were observed bilaterally in eight of nine mandibles, whose horizontal
      position was lingual against the crypt of deciduous canine. The lingual canals
      occurred from lingual foramina, and connected to the close deciduous tooth crypt
      or the mandibular canal distributing in the frontal area. CONCLUSIONS: It was
      suggested human dentition could be developed by plural mandibular and lingual
      canals.

PMID- 24026391
TI  - Bilateral subclavian origin of the bronchial arteries combined with absence of
      other origins.
AB  - There are numerous anatomical variations of the sites of origin of the bronchial
      arteries (BAs). A subclavian origin of a BA involves an aberrant artery that
      originates from the subclavian artery (SCA) or its branches. However, the
      aberrant artery usually originates directly from the SCA, and an SCA-origin BA
      arising from the branches of the SCA is rare. We herein present an extremely rare
      case of a right BA arising from the ipsilateral costocervical trunk, and a left
      BA arising from the ipsilateral thyrocervical trunk, in the absence of other
      origins of the BA. This anatomical variation was detected during pretherapeutic
      evaluation by multidetector-row computed tomography and confirmed by selective
      angiography. Recognition of these anatomic variations is important to surgical,
      diagnostic, and interventional radiologic procedures in the thorax. 

PMID- 24026392
TI  - Bilateral fused os intermetatarseum presenting as dorsal foot pain: a case
      report.
AB  - PURPOSE: Os intermetatarseum is a rare accessory bone of the forefoot and usually
      situated between the base of the first and second metatarsals. Most of the cases
      are asymptomatic and diagnosed incidentally. Here, we report a rare form of os
      intermetatarseum presented with bilateral dorsal foot pain and to the authors'
      knowledge, it is the first case which includes computerized tomography (CT) and
      magnetic resonance imaging (MRI) findings. METHODS: A 23-year-old male complained
      of localized bump at the dorsum of the both feet underwent bilateral
      anteroposterior foot radiograms which was unremarkable and then CT and MRI were
      performed. RESULTS: MRI of both feet demonstrated osseous structures in relation
      with medial os cuneiforme. Computerized tomography demonstrated bilateral os
      intermetatarsea fused with medial os cuneiforme. CONCLUSIONS: It is important for
      radiologist to know that os intermetatarseum can be presented as dorsal foot
      pain. Due to its position, it is difficult to demonstrate os intermetatarseum in
      plain radiographs, CT and MRI should be performed in clinically suggestive cases.

PMID- 24026393
TI  - Stage-specific methylome screen identifies that NEFL is downregulated by promoter
      hypermethylation in breast cancer.
AB  - Aberrant hypermethylation of promoter regions in specific genes is a key event in
      the formation and progression of breast cancers, and an increasing number of
      marker genes have been identified. However, few genes which show methylation
      change in accordance with the progression of breast cancer have been identified.
      To identify genes which consistently undergo promoter methylation alterations as
      the tumor develops from a benign to a malignant form, genome-wide methylation
      databases of breast cancer cell lines from stage I to stage IV were analyzed.
      Heatmap and cluster analysis revealed that the genome-wide methylation changes
      showed a good accordance with tumor progression. Seven out of 14,495 genes were
      found to be consistently increased alongside the promoter methylation level
      through the normal cell line to the cancer stage IV cell lines. NEFL, one of the
      in silico hypermethylated genes in cancer, showed hypermethylation and lower
      expression in the cancer cell line MDA-MB-231, as well as in cancer tissues
      (methylation, p<0.05; expression, p<0.01). The expression was restored by
      inducing demethylation of the promoter in MDA-MB-231 cells. Our findings may lend
      credence to the possibility of using tumor stage-specific alterations in
      methylation patterns as biomarkers for estimating prognosis and assessing
      treatment options for breast cancer.

PMID- 24026394
TI  - Perineal groove: a report of 2 cases.

PMID- 24026396
TI  - Numerical simulation of wind sand movement in straw checkerboard barriers.
AB  - Straw checkerboard barrier (SCB) is the most representative antidesertification
      measure and plays a significant role in antidesertification projects. Large-eddy
      simulation and discrete-particle tracing were used to numerically simulate the
      wind sand movement inside the straw checkerboard barrier (SCB), study the
      movement characteristics of sand particles, find the transverse velocities of
      sand particles and flow field, and obtain the contour of the transverse velocity
      of coupled wind field within the SCB. The results showed that 1) compared with
      that at the inlet of the SCB, the sand transport rate inside the SCB greatly
      decreases and the speed of sand grain movement also evidently drops, indicating
      that the SCB has very good sand movement preventing and fixing function; 2)
      within the SCB there exists a series of unevenly distributed eddies of wind sand
      flow, their strength decreases gradually with increasing the transverse distance;
      3) affected by eddies or reflux, sand particles carried by the wind sand flow
      have to drop forward and backward the two interior walls inside the SCB,
      respectively, forming a v-shaped sand trough; 4) the sand transport rate
      gradually decreases with increasing number of SCBs, which reveals that the
      capacity of the wind field to transport sand particles decreases. This research
      is of significance in sandstorm and land desertification control. 

PMID- 24026395
TI  - Elevated high-sensitivity C-reactive protein as a risk marker of the attenuated
      relationship between serum cholesterol and cardiovascular events at older age.
      The ARIC Study.
AB  - The relationship between cholesterol and coronary heart disease (CHD) is
      attenuated at older age. We analyzed cholesterol level as a predictor of CHD in
      8,947 participants from the Atherosclerosis Risk in Communities (ARIC) Study, a
      large multicenter cohort study that enrolled participants in 1987-1989 at 4 field
      centers in Washington County, Maryland; Forsyth County, North Carolina; Jackson,
      Mississippi; and Minneapolis, Minnesota. Participants in the present analysis had
      no history of CHD and were stratified by age (<65 or >=65 years) and high
      sensitivity C-reactive protein (hs-CRP) level (<2 or >=2 mg/L). Visit 4 (1996
      1997) was the baseline for this analysis, with follow-up through 2008.
      Cholesterol level was significantly associated with CHD among younger
      participants, and cholesterol level was similarly predictive of CHD among older
      participants with an hs-CRP level of <2 mg/L. In contrast, among older
      participants with an hs-CRP level of 2 mg/L or higher, the association of CHD
      with total cholesterol level was borderline significant (hazard ratio = 1.14, 95%
      confidence interval: 1.00, 1.29), and the association of CHD with low-density
      lipoprotein cholesterol level was nonsignificant (hazard ratio = 1.10; 95%
      confidence interval: 0.96, 1.26). Among older persons with an elevated hs-CRP
      level, cholesterol level was significantly less predictive of CHD (P < 0.05),
      whereas for those with an hs-CRP level of <2 mg/L, there was no significant
      difference compared with younger participants. In conclusion, we found that among
      the young-old, the association of cholesterol level with CHD was strong when hs
      CRP level was not elevated and weak when hs-CRP level was elevated. Therefore, hs
      CRP level could be useful for stratifying the young-old to assess the strength of
      cholesterol level in CHD risk prediction. 

PMID- 24026397
TI  - Neighborhood socioeconomic disadvantage and gestational weight gain and loss.
AB  - We explored the relationship between neighborhood socioeconomic disadvantage
      (NSED) and gestational weight gain and loss and if the association differed by
      race. A census tract level NSED index (categorized as low, mid-low, mid-high, and
      high) was generated from 12 measures from the 2000 US Census data. Gestational
      weight gain and other individual-level characteristics were derived from vital
      birth records for Allegheny County, PA for 2003-2010 (n = 55,608). Crude and
      adjusted relative risks were estimated using modified multilevel Poisson
      regression models to estimate the association between NSED and excessive and
      inadequate gestational weight gain (GWG) and weight loss (versus adequate GWG).
      Black women lived in neighborhoods that were more likely to be socioeconomically
      disadvantaged compared to white women. Almost 55% of women gained an excessive
      amount of weight during pregnancy, and 2% lost weight during pregnancy. Black
      women were more likely than white women to have inadequate weight gain or weight
      loss. Mid-high (aRR = 1.3, 95% CI 1.2, 1.3) and high (aRR = 1.5, 95% CI 1.5, 1.6)
      NSED compared to low NSED was associated with inadequate weight gain while NSED
      was not associated with excessive weight gain. Among black women, high versus low
      NSED was associated with weight loss during pregnancy (RR = 1.6, 95% CI 1.1,
      2.5). Among white women, each level of NSED compared to low NSED was associated
      with weight loss during pregnancy. This study demonstrates how neighborhood
      socioeconomic characteristics can contribute to our understanding of inadequate
      weight gain and weight loss during pregnancy, having implications for future
      research and interventions designed to advance pregnancy outcomes.

PMID- 24026399
TI  - Carbon precipitation from heavy hydrocarbon fluid in deep planetary interiors.
AB  - The phase diagram of the carbon-hydrogen system is of great importance to
      planetary sciences, as hydrocarbons comprise a significant part of icy giant
      planets and are involved in reduced carbon-oxygen-hydrogen fluid in the deep
      Earth. Here we use resistively- and laser-heated diamond anvil cells to measure
      methane melting and chemical reactivity up to 80 GPa and 2,000 K. We show that
      methane melts congruently below 40 GPa. Hydrogen and elementary carbon appear at
      temperatures of >1,200 K, whereas heavier alkanes and unsaturated hydrocarbons
      (>24 GPa) form in melts of >1,500 K. The phase composition of carbon-hydrogen
      fluid evolves towards heavy hydrocarbons at pressures and temperatures
      representative of Earth's lower mantle. We argue that reduced mantle fluids
      precipitate diamond upon re-equilibration to lighter species in the upwelling
      mantle. Likewise, our findings suggest that geophysical models of Uranus and
      Neptune require reassessment because chemical reactivity of planetary ices is
      underestimated. 

PMID- 24026398
TI  - Co-expressed genes prepositioned in spatial neighborhoods stochastically
      associate with SC35 speckles and RNA polymerase II factories.
AB  - Chromosomally separated, co-expressed genes can be in spatial proximity, but
      there is still debate about how this nuclear organization is achieved. Proposed
      mechanisms include global genome organization, preferential positioning of
      chromosome territories, or gene-gene sharing of various nuclear bodies. To
      investigate this question, we selected a set of genes that were co-expressed upon
      differentiation of human multipotent stem cells. We applied a novel multi
      dimensional analysis procedure which revealed that prior to gene expression, the
      relative position of these genes was conserved in nuclei. Upon stem cell
      differentiation and concomitant gene expression, we found that co-expressed genes
      were closer together. In addition, we found that genes in the same 1-MUm-diameter
      neighborhood associated with either the same splicing speckle or to a lesser
      extent with the same transcription factory. Dispersal of speckles by
      overexpression of the serine-arginine (SR) protein kinase cdc2-like kinase Clk2
      led to a significant drop in the number of genes in shared neighborhoods. We
      demonstrate quantitatively that the frequencies of speckle and factory sharing
      can be explained by assuming stochastic selection of a nuclear body within a
      restricted sub-volume defined by the original global gene positioning present
      prior to gene expression. We conclude that the spatial organization of these
      genes is a two-step process in which transcription-induced association with
      nuclear bodies enhances and refines a pre-existing global organization. 

PMID- 24026400
TI  - Health care costs of complex perianal fistula in Crohn's disease.
AB  - AIM: To evaluate the use of health care resources and the associated costs of
      complex perianal Crohn's disease (CD) from the National Health System
      perspective. METHODS: We conducted a multicenter, retrospective, observational
      study in which gastroenterologists from 11 hospitals in the Community of Madrid
      took part. Data was collected on the direct healthcare resources (pharmacological
      treatments, surgical procedures, laboratory/diagnostic tests, visits to
      specialists and emergency departments, and hospitalizations) consumed by 97 adult
      patients with complex perianal CD which was active at some point between January
      1, 2005, and case history review. RESULTS: We recorded 527 treatments: 73.1%
      pharmacological (32.3% antibiotic, 20.5% immunomodulator, 20.3% biological) and
      26.9% surgical. Mean annual global cost was ?8,289/patient, 75.3% (?6,242) of
      which was accounted for by pharmacological treatments (?13.44 antibiotics; ?1,136
      immunomodulators; ?5,093 biological agents), 12.4% (?1,027) by hospitalizations
      and surgery, 7.7% (?640) by medical visits, 4.2% (?350) by laboratory/diagnostic
      tests, and 0.4% (?30) by emergency department visits. CONCLUSIONS:
      Pharmacological therapies, and in particular biological agents, are the main cost
      driver in complex perianal CD; costs due to surgery and hospitalizations are much
      lower.

PMID- 24026401
TI  - Dyssynergic defecation: a treatable cause of persistent symptoms when
      inflammatory bowel disease is in remission.
AB  - BACKGROUND: Introduction of biologic agents in inflammatory bowel disease (IBD)
      has increased the likelihood of disease remission. Despite resolution of active
      inflammation, a subset of IBD patients report persistent defecatory symptoms.
      AIM: To evaluate a group of patients with inflammatory bowel disease with
      suspected functional defecatory disorders, by use of anorectal manometric testing
      and subsequent biofeedback therapy. METHODS: A group of IBD patients with
      persistent defecatory problems despite clinical improvement were included in this
      study. These patients had no evidence of left-sided disease. Endoscopic and
      radiographic study findings and timing in relation to the manometry study were
      recorded. Anorectal manometry was performed by the standard protocol and included
      rectal sensory assessment, ability to expel a balloon, and pressure dynamics with
      simulated defecation. RESULTS: Thirty IBD patients (Crohn's 23 patients;
      ulcerative colitis six patients) presented with defecatory disorders including
      constipation (67%) increased stooling (10%), and rectal urgency and/or
      incontinence and rectal pain (6%). All but one patient had anorectal manometric
      criteria of dyssynergia (presence of anismus motor pattern and inability to expel
      the balloon). Of the patients who completed biofeedback therapy, 30% had a
      clinically significant (>=7-point) improvement in SIBDQ score, with a reduction
      in health-care utilization after a six-month period (p=0.02). CONCLUSIONS:
      Despite remission, some inflammatory bowel disease patients have persistent
      defecatory symptoms. Defecatory symptoms may not be predictive of an underlying
      inflammatory disorder. Lack of inflammatory activity and absence of left-sided
      disease should prompt investigation of functional disorders. Anorectal manometric
      testing and biofeedback therapy for patients with a diagnosis of dyssynergia may
      be a useful therapy.

PMID- 24026402
TI  - Radiation exposure from diagnostic imaging studies among patients with
      inflammatory bowel disease in a safety-net health-care system.
AB  - BACKGROUND/AIMS: Radiographic imaging studies are important in the management of
      patients with inflammatory bowel disease (IBD), but are associated with radiation
      exposure. IBD patients in a safety-net health-care system may be at risk of high
      exposure to radiation. Our purpose was to identify associations of high-dose
      radiation exposure among an ethnically diverse cohort of IBD patients in a safety
      net health-care system. METHODS: A study was performed on patients with IBD
      receiving care from the Harris County Hospital District. Radiation exposure was
      calculated using total number of imaging studies performed between from 2000 and
      2010 and estimates of radiation dose per study. Associations of high-dose
      radiation exposure, defined as a cumulative effective dose (CED) >50 mSv, were
      identified by using univariate and multivariate logistic regression. RESULTS: The
      study cohort of 278 patients with IBD was ethnically diverse, with 30 %
      Caucasian, 44 % African-American, and 26 % Hispanic. The median CED was 10.40 mSv
      (SD 20.02). Annualized radiation doses were 3.45 mSv/year among patients with
      Crohn's disease (CD) and 1.27 mSv/year among patients with ulcerative colitis, p
      < 0.02. Approximately 13 % of IBD patients received a CED >50 mSv. There were no
      differences in radiation exposure based on age, gender, or race/ethnicity.
      CONCLUSIONS: A small proportion of IBD patients in a safety-net health-care
      system received high doses of diagnostic radiation exposure. Use of diagnostic
      imaging studies that limit radiation exposure should be encouraged.

PMID- 24026404
TI  - Macro-aspartate aminotransferase: two-year follow-up of three patients in China.

PMID- 24026403
TI  - Use of exclusive enteral nutrition is just as effective as corticosteroids in
      newly diagnosed pediatric Crohn's disease.
AB  - BACKGROUND: The efficacy of exclusive enteral nutrition (EEN) in induction of
      remission in pediatric Crohn's disease (CD) is reported to be equivalent to that
      of corticosteroids (CS). AIMS: Our objective was to compare the efficacy of EEN
      and CS in inducing remission in pediatric onset CD and the effects of the
      treatment on nutritional status and bone mineral density (BMD). METHODS: Medical
      charts were retrospectively studied for patients diagnosed with CD between 2000
      and 2010 at the Stollery children's hospital in Edmonton, Alberta. Anthropometric
      and dual-energy X-ray absorptiometry (DXA) data were collected to assess effects
      of therapy; clinical remission, relapse, and severity were defined on the basis
      of the pediatric Crohn's disease activity index. RESULTS: To induce remission at
      first presentation, 36 patients (mean age 12.9 years) received EEN and 69 (mean
      age 11.2 years) received CS. Remission (88.9% in the EEN group versus 91.3% in
      the CS group (p=0.73) at 3 months) and relapse (40.6 vs. 28.6%, respectively
      (p=0.12) over 12 months) were similar in both treatment groups. Thirty-four
      patients had paired DXA scans at the time of diagnosis and one year later: 16
      given EEN and 18 given CS. Change in BMD spine z-scores based on bone age
      adjusted for height and chronological age was greater for EEN patients but not
      statistically significant (Deltaz-score 0.30 vs. 0.03, p=0.28). CONCLUSIONS: EEN
      has similar efficacy to corticosteroids; however, EEN may lead to better BMD
      accrual. EEN should be preferred to corticosteroids as first-line therapy for
      induction of remission in pediatric CD.

PMID- 24026405
TI  - The safety and efficacy of therapeutic ERCP in the pediatric population performed
      by adult gastroenterologists.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is much less
      commonly performed in the pediatric population compared to adults. As a result,
      few pediatric gastroenterologists receive adequate training in ERCP. At many
      institutions, pediatric ERCP is performed by adult gastroenterologists not
      formally trained in pediatric gastroenterology. AIM: The purpose of this study
      was to assess the efficacy and safety of ERCP performed in pediatric patients by
      adult gastroenterologists in a single tertiary care center. METHODS: We performed
      a retrospective analysis of pooled endoscopic procedures in pediatric patients
      (age<18 years) at the University of Maryland Medical Center, between 2003 and
      2011, by two adult therapeutic endoscopists. Neither endoscopist had formal
      training in pediatric ERCP prior to 2003. Outcome measures included the procedure
      indications, cannulation success rates, procedure success rates, type of
      anesthesia, therapeutic interventions, frequency and type of procedure related
      complications, and technical complexity. RESULTS: Forty-five patients were
      included with a mean age of 12 years (range 6-17). There were a total of 70 ERCP
      procedures. Choledocholithiasis was the most common indication. Modes of
      anesthesia included monitored anesthesia care (31, 44.3%), general anesthesia
      (22, 31.4%) and moderate conscious sedation (17, 24.3%). The papilla cannulation
      success rate was 98.6% (69/70). Therapeutic maneuvers included 31 biliary
      sphincterotomies, ten pancreatic sphincterotomies, 17 pancreatic duct stents, 16
      bile duct stents, two cystgastrostomy stents, four biliary stricture dilations,
      one minor papillotomy site dilation, one mechanical lithotripsy and one
      ampullectomy. The procedural success rate was 97.1% (68/70). The overall
      complication rate was 7.1% (5/70) with a post-ERCP pancreatitis rate of 4.3%
      (3/70). Complications included infection (moderate-1), bleeding (moderate-1), and
      post-ERCP pancreatitis (mild-1, moderate-2). CONCLUSIONS: ERCP procedures in
      pediatric patients can be safely and efficaciously performed by adult
      gastroenterologists trained in advanced endoscopy.

PMID- 24026406
TI  - MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN.
AB  - BACKGROUND: Our previous studies show that microRNA-92a (miR-92a) is
      overexpressed in colorectal cancer (CRC) and is thought to be correlated with the
      development of the cancer. However, its biological role in CRC remains poorly
      understood. AIMS: The aim of the study was to determine the role of miR-92a and
      to elucidate its regulatory mechanism in CRC. METHODS: The expression levels of
      miR-92a and phosphatase and tensin homologue (PTEN) were detected by qRT-PCR and
      western blot. MTT, migration and invasion assays were used to examine the
      proliferation, migration and invasion of pre-miR-92a transfected SW480 cells, and
      a mouse model was used to investigate tumorigenesis. In addition, the regulation
      of PTEN by miR-92a was evaluated by qRT-PCR, western blot and luciferase reporter
      assays. RESULTS: The expression of miR-92a was significantly up-regulated in the
      tissues of CRC patients with lymph node metastasis. The ectopic expression of miR
      92a enhanced CRC cell proliferation, migration and invasion. Similar results were
      found in xenograft assay performed in nude mice. Up-regulation of miR-92a induced
      EMT in CRC cells. There was an inverse correlation between the levels of miR-92a
      and PTEN in CRC tissues. The overexpression of miR-92a in CRC cells decreased
      PTEN expression at the translational level, and decreased PTEN-driven luciferase
      reporter activity. CONCLUSIONS: Our results demonstrated that miR-92a induced EMT
      and regulated cell growth, migration and invasion in the SW480 cells, at least
      partially, via suppression of PTEN expression. MiR-92a may serve as a novel
      therapeutic target in colorectal cancer.

PMID- 24026407
TI  - Ultrasound-guided endoscopic biliary drainage: a useful drainage method for
      biliary decompression in patients with biliary obstructions.
AB  - BACKGROUND: Endoscopic retrograde cholangiopancreatography with fluoroscopy
      guidance is a well-established technique for providing biliary drainage in
      patients with biliary obstructions. However, fluoroscopic facilities may not
      always be available and fluoroscopy carries a risk of radiation exposure. AIM: We
      retrospectively compared the procedure success rate and efficacy of ultrasound
      guided endoscopic biliary drainage (UG-EBD) and fluoroscopy-guided endoscopic
      biliary drainage (FG-EBD) in patients with biliary obstructions. METHODS:
      Patients who had received either UG-EBD or FG-EBD were included in the study.
      Main outcome measurements included the procedure success rate, procedure time,
      and clinical response. RESULTS: A total of 125 patients who had undergone UG-EBD
      (n = 63) and FG-EBD (n = 62) were identified. The total procedure success rate
      was 93.7 % in the UG-EBD group and 96.8 % in the FG-EBD group without statistical
      difference. Also, no significant difference was found in the procedure success
      rate of lower or upper/middle obstructions of the common bile duct (CBD) between
      the 2 groups. The mean procedure time was not different between the 2 groups [UG
      EBD group 24.54 (9.52) min vs. FG-EBD group 21.74 (8.77) min, p = 0.09]. There
      were no differences in the normalization of clinical and laboratory parameters
      and immediate complication between the 2 groups. CONCLUSIONS: Endoscopic biliary
      drainage (EBD) under US-guidance and under fluoroscopy guidance is equally
      effective and safe for patients with lower or upper/middle obstructions of the
      CBD. The UG-EBD technique is especially suitable for special patients, such as
      critically ill patients, pregnant woman, etc.

PMID- 24026408
TI  - Asymptomatic Mycoplasma genitalium infection amongst marginalised young people
      accessing a youth health service in Melbourne.
AB  - We conducted a study to establish the prevalence of Mycoplasma genitalium amongst
      asymptomatic young people experiencing homelessness in the context of
      comprehensive health care delivery. All asymptomatic young people at risk of
      sexually transmitted infections were offered urinary polymerase chain reaction
      testing for M. genitalium whilst being tested for Chlamydia trachomatis and
      Neisseria gonorrhoeae over a four-month period in 2012. Those who tested positive
      were notified of the infection and offered treatment. Sixty asymptomatic young
      people (36 female and 24 male) were tested for M. genitalium, identifying eight
      cases (13%) (six female and two male). Ten young people (17%) tested positive for
      C. trachomatis, three (5%) of whom were positive for both M. genitalium and C.
      trachomatis. There were no cases of N. gonorrhoeae. Of the eight cases of M.
      genitalium, seven were contactable and five were treated at our clinic with
      azithromycin 1 g stat. Two of the five returned after a month for a test of cure,
      identifying one resistant infection. Further data on the epidemiology of M.
      genitalium are required before testing recommendations can be made; however,
      consideration should be given to testing for M. genitalium in settings where
      other sexually transmitted infections are prevalent.

PMID- 24026410
TI  - Simultaneous saccharification of inulin and starch using commercial glucoamylase
      and the subsequent bioconversion to high titer sorbitol and gluconic acid.
AB  - A new bioprocess for production of sorbitol and gluconic acid from two low-cost
      feedstocks, inulin and cassava starch, using a commercially available enzyme was
      proposed in this study. The commercial glucoamylase GA-L NEW from Genencor was
      found to demonstrate a high inulinase activity for hydrolysis of inulin into
      fructose and glucose. The glucoamylase was used to replace the expensive and not
      commercially available inulinase enzyme for simultaneous saccharification of
      inulin and starch into high titer glucose and fructose hydrolysate. The glucose
      and fructose in the hydrolysate were converted into sorbitol and gluconic acid
      using immobilized whole cells of the recombinant Zymomonas mobilis strain. The
      high gluconic acid concentration of 193 g/L and sorbitol concentration of 180 g/L
      with the overall yield of 97.3 % were obtained in the batch operations. The
      present study provided a practical production method of sorbitol and gluconic
      acid from low cost feedstocks and enzymes.

PMID- 24026411
TI  - Comparative bioactive studies between wild plant and callus culture of Tephrosia
      tinctoria pers.
AB  - Tephrosia tinctoria, a perennial under shrub of Fabaceae family, is endemic to
      Western Ghats. In this study, friable whitish yellow callus was developed after
      45 days using Murashige and Skoog medium supplemented with 2,4
      dichlorophenoxyacetic acid (2.0 mg/l) + 6-benzylaminopurine (0.5 mg/l) in various
      explants of T. tinctoria. The ethyl acetate extracts of leaf (LE), stem (SE), and
      root (RE) were compared with leaf (LCE), stem (SCE), and root (RCE) derived
      callus, for antioxidant and antiproliferative activities. The SE possessed the
      highest phenolic and flavonoid content among all the extracts tested and showed a
      significant antioxidant assays. The study of anticancer activity on human
      hepatocellular carcinoma (HepG2) cell line revealed that the callus extracts
      especially RCE possessed significant inhibition of cell growth (IC50 20 MUg/ml)
      at 72 h treatment period on analysis with MTT assay. The apoptotic cell death was
      observed through DNA fragmentation analysis in HepG2 cells treated with the T.
      tinctoria extracts. The gas chromatography-mass spectrometry finger printing
      profile showed that more than 60 % percentage of metabolites are similar in both
      SE and SCE. The higher percentage area of antioxidant compound (stigmast-4-en-3
      one) was observed in SE (2.01 %) and higher percentage area of anticancer
      compound (phenol, 2,4-bis(1,1-dimethylethyl)) in SCE (0.91 %). In addition to
      that, callus extracts contain squalene, which is used for target deliver and also
      used as anticancer drug. Thus, the present study revealed that the T. tinctoria
      has potent antioxidant and antiproliferative activity and the callus culture can
      be used for the production of the bioactive compounds due to the endemic nature
      of this plant.

PMID- 24026412
TI  - Quantitative analysis of previously identified propionate-oxidizing bacteria and
      methanogens at different temperatures in an UASB reactor containing propionate as
      a sole carbon source.
AB  - Propionate degradation is crucial for maintaining the efficiency and stability of
      an anaerobic reactor. However, there was little information about the effects of
      ecological factor on propionate-oxidizing bacteria (POB). In current research,
      quantitative real-time fluorescence polymerase chain reaction (QPCR) of some
      identified POB and methanogens with a decrease in temperature in an upflow
      anaerobic sludge bed (UASB) reactor containing propionate as sole carbon source
      was investigated. The results showed that there were at least four identified
      POB, including Pelotomaculum schinkii, Pelotomaculum propionicum, Syntrophobacter
      fumaroxidans, and Syntrophobacter sulfatireducens, observed in this UASB reactor.
      Among them, P. schinkii was dominated during the whole operational period. Its
      quantity was 1.2 * 10(4) 16S rRNA gene copies per nanogram of DNA at 35  degrees
      C. A decrease in temperature from 35 to 30  degrees C led to P. schinkii to be
      increased by 1.8 times and then it was gradually reduced with a decrease in
      temperature from 30 to 25, 20, and 18  degrees C stepwise. A decrease in
      temperature from 35 to 20  degrees C did not make the amount of methanogens
      markedly changed, but hydrogenotrophic methanogens (Methanospirillum) and
      acetotrophic methanogens (Methanosaeta) at 18  degrees C were increased by an
      order of magnitude and 1.0 time, respectively, compared with other experimental
      conditions.

PMID- 24026413
TI  - Construction and operation of microbial fuel cell with Chlorella vulgaris
      biocathode for electricity generation.
AB  - In this study, a modified microbial fuel cell (MFC) with a tubular
      photobioreactor (PHB) configuration as a cathode compartment was constructed by
      introducing Chlorella vulgaris to the cathode chamber used to generate oxygen in
      situ. Two types of cathode materials and light/dark cycles were used to test the
      effect on MFC with algae biocathode. Results showed that the use of algae is an
      effective approach because these organisms can act as efficient in situ
      oxygenators, thereby facilitating the cathodic reaction. Dissolved oxygen and
      voltage output displayed a clear light positive response and were drastically
      enhanced compared with the abiotic cathode. In particular, carbon paper-coated Pt
      used as a cathode electrode increased voltage output at a higher extent than
      carbon felt used as an electrode. The maximum power density of 24.4 mW/m(2) was
      obtained from the MFC with algae biocathode which utilized the carbon paper
      coated Pt as the cathode electrode under intermittent illumination. This density
      was 2.8 times higher than that of the abiotic cathode. Continuous illumination
      shortened the algal lifetime. These results demonstrated that intermittent
      illumination and cathode material-coated catalyst are beneficial to a more
      efficient and prolonged operation of MFC with C. vulgaris biocathode.

PMID- 24026414
TI  - Comparative antioxidant study of stem and stem induced callus of Phyllanthus
      fraternus webster-an important antiviral and hepatoprotective plant.
AB  - Phyllanthus fraternus is widely used in the cure of various liver diseases and
      possess antiviral properties especially against hepatitis virus. In the present
      study, evaluation of the antioxidant activity of stem and calli induced from stem
      has been done by different assays. Extraction was done by standard method in
      water and ethanol. Total antioxidant capacity was measured by 1, 1-diphenyl-2
      picrylhydrazyl free radical scavenging method. Lipid peroxidation was measured in
      terms of thiobarbituric acid-reactive substances (TBARS) by using egg yolk
      homogenates as lipid-rich media, and superoxide radical scavenging activity was
      measured using riboflavin-light-nitro blue tetrazolium assay. Reducing power was
      determined on the basis of Fe(3+)-Fe(2+) transformation in the presence of the
      extract. In addition to the antioxidant activity, polyphenolic compounds like
      total phenolics and flavonoids were also measured by spectroscopic method.
      Results showed that the ethanolic extract of stem is more potent in antioxidant
      activity than its aqueous extract and ethanolic extract of calli. A significant
      correlation between antioxidant capacity and polyphenolic content and reducing
      potential was observed, indicating that phenolic compounds and reducers present
      in extract are major contributors to the antioxidant potential. Thus, this plant
      extract could be used as a potent natural antioxidant. 

PMID- 24026415
TI  - Kinetic study on cephamycin C degradation.
AB  - Cephamycin C (CepC) is a beta-lactam antibiotic that belongs to the cephalosporin
      class of drugs. This compound stands out from other cephalosporins for its
      greater resistance to beta-lactamases, which are enzymes produced by pathogenic
      microorganisms that present a major mechanism of bacterial resistance to beta
      lactam antibiotics. Cephamycin C is produced by the bacterium Streptomyces
      clavuligerus. Knowledge about the stability of the compound under different
      values of pH is important for the development of the process of production,
      extraction, and purification aimed at obtaining higher yields. Therefore, the
      stability of cephamycin C under different pH levels (2.2, 6.0, 7.0, 7.6, and 8.7)
      at 20  degrees C was evaluated in this study. Ultrafiltered broth from batch
      fermentations of S. clavuligerus was used in the trials. The results indicated
      that cephamycin C is a more stable compound than other beta-lactam compounds such
      as penicillin and clavulanic acid. A higher degradation rate was observed at very
      acidic or basic pH levels, while this rate was lower at quasi-neutral pH levels.
      After 100 h of trial, the initial CepC showed 46 % degradation at pH 2.2, 71 %
      degradation at pH 8.7, and varied from 15 to 20 % at quasi-neutral pH levels.

PMID- 24026416
TI  - Highly efficient method towards in situ immobilization of invertase using
      cryogelation.
AB  - A novel method was developed for the immobilization of Saccharomyces cerevisiae
      invertase within supermacroporous polyacrylamide cryogel and was used to produce
      invert sugar. First, the cross-linking of invertase with soluble
      polyglutaraldehyde (PGA) was carried out prior to immobilization in order to
      increase the bulkiness of invertase and thus preventing the leakage of the cross
      linked enzyme after immobilization by entrapment. And then, in situ
      immobilization of PGA cross-linked invertase within cryogel synthesis was
      achieved by free radical polymerization in semi-frozen state. The method resulted
      in 100 % immobilization and 74 % activity yields. The immobilized invertase
      retained all the initial activity for 30 days and 30 batch reactions.
      Immobilization had no effect on optimum temperature and it was 60  degrees C for
      both free and immobilized enzyme. However, optimum pH was affected upon
      immobilization. Optimum pH values for free and immobilized enzyme were 4.5 and
      5.0, respectively. The immobilized enzyme was more stable than the free enzyme at
      high pH and temperatures. The kinetic parameters for free and immobilized
      invertase were also determined. The newly developed method is simple yet
      effective and could be used for the immobilization of some other enzymes and
      microorganisms.

PMID- 24026417
TI  - Capsule Commentary on Duru, et al., potential savings associated with drug
      substitution in Medicare Part D: the Translating Research into Action for
      Diabetes (TRIAD) Study.

PMID- 24026418
TI  - Invasive aspergillosis.

PMID- 24026419
TI  - Janet's prayer.

PMID- 24026420
TI  - Theoretical investigations into the nucleation of silica growth in basic solution
      part II--derivation and benchmarking of a first principles kinetic model of
      solution chemistry.
AB  - A kinetic model of silicate oligomerization in water, up to and including
      tetramer formation, has been compiled exclusively from rate constants derived
      from transition state theory based on either quantum chemical data (derived under
      a hybrid solvation framework) for all bond breaking-forming reactions, or using
      empirically-based approximated pKa's and diffusion coefficients for rate
      constants of pH-based and bimolecular steps. The rate constants, based on an
      exhaustive search of all relevant elementary steps, form the basis of our kinetic
      model; numerical solution of the resulting rate equations allows the simulation
      of the reaction system, given a set of initial conditions and with almost no
      restriction on concentrations, pH, or reaction time, in a matter of only minutes.
      The model, which we believe contains all possible isomers of both neutral and
      singly anionic clusters, has been extensively benchmarked and reproduces a number
      of important experimental observations in the range pH ~ 4-10. In particular, it
      provides a good description of the dominant products; product yields and reaction
      times (also as a function of pH) are in agreement with experiment; the linear
      relationship between the log of the rate of silica dissolution and pH is well
      reproduced; the origin of silica scaling naturally arises; and we can also
      simulate the observed fourth order dependence of the rate of monomer consumption
      on H4SiO4 concentration. This should be a general approach to exploring solution
      phase chemistry, and could be a useful complement to more conventional molecular
      dynamics and Monte Carlo modelling approaches in understanding complex reaction
      networks in solution. 

PMID- 24026421
TI  - A new form of rapid binocular plasticity in adult with amblyopia.
AB  - Amblyopia is a neurological disorder of binocular vision affecting up to 3% of
      the population resulting from a disrupted period of early visual development.
      Recently, it has been shown that vision can be partially restored by intensive
      monocular or dichoptic training (4-6 weeks). This can occur even in adults owing
      to a residual degree of brain plasticity initiated by repetitive and successive
      sensory stimulation. Here we show that the binocular imbalance that characterizes
      amblyopia can be reduced by occluding the amblyopic eye with a translucent patch
      for as little as 2.5 hours, suggesting a degree of rapid binocular plasticity in
      adults resulting from a lack of sensory stimulation. The integrated binocular
      benefit is larger in our amblyopic group than in our normal control group. We
      propose that this rapid improvement in function, as a result of reduced sensory
      stimulation, represents a new form of plasticity operating at a binocular site. 

PMID- 24026422
TI  - Genetic interactions found between calcium channel genes modulate amyloid load
      measured by positron emission tomography.
AB  - Late-onset Alzheimer's disease (LOAD) is known to have a complex, oligogenic
      etiology, with considerable genetic heterogeneity. We investigated the influence
      of genetic interactions between genes in the Alzheimer's disease (AD) pathway on
      amyloid-beta (Abeta) deposition as measured by PiB or AV-45 ligand positron
      emission tomography (PET) to aid in understanding LOAD's genetic etiology.
      Subsets of the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohorts were
      used for discovery and for two independent validation analyses. A significant
      interaction between RYR3 and CACNA1C was confirmed in all three of the
      independent ADNI datasets. Both genes encode calcium channels expressed in the
      brain. The results shown here support previous animal studies implicating
      interactions between these calcium channels in amyloidogenesis and suggest that
      the pathological cascade of this disease may be modified by interactions in the
      amyloid-calcium axis. Future work focusing on the mechanisms of such
      relationships may inform targets for clinical intervention. 

PMID- 24026424
TI  - Cathepsin D stimulates the activities of secreted plasminogen activators in the
      breast cancer acidic environment.
AB  - Two proteases cathepsin D (cath D) and urokinase plasminogen activator (uPA) are
      tissue markers associated with an increased risk of metastasis in breast cancer.
      We investigated whether cath D, the major aspartyl protease overexpressed by
      breast cancer cells can trigger a proteolytic cascade via activation of
      plasminogens at the extracellular pH measured in hypoxic tumors. The effects of
      the aspartyl protease inhibitor pepstatin on the plasminogen activator (PA)
      system were analysed by conditioning media of human MDA-MB231 breast cancer cells
      at pH 6.6 and pH 7.4. Zymography analysis of culture media showed that pepstatin
      inhibited the secreted activity of tissue-type plasminogen activator (tPA) but
      not that of uPA. tPA was identified on the basis of the molecular weight, the
      immunoreactivity with relevant antibodies and the resistance to amiloride, a
      specific uPA inhibitor. The secreted tPA activity measured by a chromogenic assay
      in the presence of amiloride was also inhibited by pepstatin at pH 6.6.
      Surprisingly, pepstatin did not affect secreted tPA protein concentration but
      markedly increased the amount of the secreted plasminogen activator inhibitor-1
      (PAI-1). We conclude that cath D overexpressed by these cells, stimulates at pH
      6.6, but not at neutral pH, the extracellular PA proteolytic activity indirectly
      via PAI-1 proteolysis. This suggests that cath D at acidic pH close to the
      hypoxic regions of solid tumors, contributes to trigger a proteolytic cascade
      facilitating cancer cell invasion and metastasis.

PMID- 24026423
TI  - A genome- and phenome-wide association study to identify genetic variants
      influencing platelet count and volume and their pleiotropic effects.
AB  - Platelets are enucleated cell fragments derived from megakaryocytes that play key
      roles in hemostasis and in the pathogenesis of atherothrombosis and cancer.
      Platelet traits are highly heritable and identification of genetic variants
      associated with platelet traits and assessing their pleiotropic effects may help
      to understand the role of underlying biological pathways. We conducted an
      electronic medical record (EMR)-based study to identify common variants that
      influence inter-individual variation in the number of circulating platelets (PLT)
      and mean platelet volume (MPV), by performing a genome-wide association study
      (GWAS). We characterized genetic variants associated with MPV and PLT using
      functional, pathway and disease enrichment analyses; we assessed pleiotropic
      effects of such variants by performing a phenome-wide association study (PheWAS)
      with a wide range of EMR-derived phenotypes. A total of 13,582 participants in
      the electronic MEdical Records and GEnomic network had data for PLT and 6,291
      participants had data for MPV. We identified five chromosomal regions associated
      with PLT and eight associated with MPV at genome-wide significance (P < 5E-8). In
      addition, we replicated 20 SNPs [out of 56 SNPs (alpha: 0.05/56 = 9E-4)]
      influencing PLT and 22 SNPs [out of 29 SNPs (alpha: 0.05/29 = 2E-3)] influencing
      MPV in a published meta-analysis of GWAS of PLT and MPV. While our GWAS did not
      find any new associations, our functional analyses revealed that genes in these
      regions influence thrombopoiesis and encode kinases, membrane proteins, proteins
      involved in cellular trafficking, transcription factors, proteasome complex
      subunits, proteins of signal transduction pathways, proteins involved in
      megakaryocyte development, and platelet production and hemostasis. PheWAS using a
      single-SNP Bonferroni correction for 1,368 diagnoses (0.05/1368 = 3.6E-5)
      revealed that several variants in these genes have pleiotropic associations with
      myocardial infarction, autoimmune, and hematologic disorders. We conclude that
      multiple genetic loci influence interindividual variation in platelet traits and
      also have significant pleiotropic effects; the related genes are in multiple
      functional pathways including those relevant to thrombopoiesis.

PMID- 24026425
TI  - Noise-equivalent sensitivity of photoacoustics.
AB  - The fundamental limitations of photoacoustic microscopy for detecting optically
      absorbing molecules are investigated both theoretically and experimentally. We
      experimentally demonstrate noise-equivalent detection sensitivities of 160,000
      methylene blue molecules (270 zeptomol or 2.7*10-19  mol) and 86,000 oxygenated
      hemoglobin molecules (140 zeptomol) using narrowband continuous-wave
      photoacoustics. The ultimate sensitivity of photoacoustics is fundamentally
      limited by thermal noise, which can present in the acoustic detection system as
      well as in the medium itself. Under the optimized conditions described herein and
      using commercially available detectors, photoacoustic microscopy can detect as
      few as 100s of oxygenated hemoglobin molecules. Realizable improvements to the
      detector may enable single molecule detection of select molecules.

PMID- 24026427
TI  - Lenalidomide with dexamethasone treatment for relapsed/refractory myeloma
      patients in Korea-experience from 110 patients.
AB  - We conducted a retrospective analysis of lenalidomide with dexamethasone for
      patients with relapsed/refractory multiple myeloma (RRMM) who were treated within
      the Korean patient access program. Lenalidomide has been approved for RRMM for
      several years in Europe and North America, but has not been accessible to Asian
      patients in the past. Between 2008 and 2012, 110 patients from 20 hospitals were
      enrolled. The overall response rate (ORR) was 43.6 % with 15.4 % of very good
      partial response (VGPR) or better. The median time to progression (TTP) in this
      heavily pretreated patient population was 8.0 months, and median overall survival
      (OS) was 23 months. Hematologic toxicities, fatigue, anorexia, and constipation
      were the most common adverse events. The number of previous treatment lines,
      previous exposure to thalidomide, refractoriness to thalidomide and bortezomib,
      pretreatment white blood cell count (WBC), platelet count, t(14;16), and 17p
      deletion were significant prognostic factors for TTP, and creatinine clearance,
      refractoriness to thalidomide and bortezomib, performance status, platelet count,
      and 17p deletion were significant for OS in univariate analysis. In multivariate
      analysis, WBC and platelet count were significant prognostic factors for TTP and
      performance status for OS. For Korean myeloma patients, lenalidomide showed
      considerable efficacy, and toxicities were comparable to the data published in
      Europe and North America.

PMID- 24026429
TI  - Anti-inflammatory and antioxidant activities of phenolic compounds from Desmodium
      caudatum leaves and stems.
AB  - Four flavanonols (1-4), one xanthone (5), and three flavonoid glycosides (6-8),
      were isolated from the leaves and stems of Desmodium caudatum. Their structures
      were elucidated by comparing spectroscopic data with reported values. The anti
      inflammatory activity of the isolated compounds was investigated in
      lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among
      them, compounds 1 and 2 exhibited inhibitory effects on LPS-induced IL-6, IL-12
      p40, and TNF-alpha production with IC50 values ranging from 6.0 to 29.4 MUM.
      Compound 5 exhibited 1,1-diphenyl-2-picrylhydrazyl radical and intracellular
      reactive oxygen species scavenging activity in human HaCaT keratinocytes. These
      results warrant further studies of the potential anti-inflammatory and
      antioxidant benefits of compounds from D. caudatum.

PMID- 24026428
TI  - Anticancer potential of rhamnocitrin 4'-beta-D-galactopyranoside against N
      diethylnitrosamine-induced hepatocellular carcinoma in rats.
AB  - The hepatoprotective activity of flavonoid rhamnocitrin 4'-beta-D
      galactopyranoside (RGP) obtained from leaves of Astragalus hamosus L. against N
      diethylnitrosamine (DENA)-induced hepatic cancer in Wistar albino rats was
      evaluated. Hepatic cancer in rats was induced by single-dose intraperitoneal
      administration of DENA (200 mg/kg). Induction of hepatic cancer was confirmed
      after 7 days of DENA administration by measurement of elevated level of serum
      alpha-feto protein (AFP). Administration of DENA in a single dose lofted the
      levels of serum biochemical parameters like alanine aminotransferase, aspartate
      aminotransferase, alkaline phosphatase, total bilirubin, total protein and AFP.
      Antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx), glutathione-S-transferase (GST) and lipid per oxidation (LPO)
      were annealed significantly by administration of RGP in a dose-dependant manner.
      The histopathological examination of rat liver section was found to reinforce the
      biochemical observations significantly. It was observed that a substantial and
      dose-dependent reversal of DENA-diminished activity of antioxidant enzymes like
      SOD, CAT, GPx, GST and the reduced DENA-elevated level of LPO with a marked
      change. Any elevation in the levels of serum markers along with suppression of
      free radical formation by scavenging the hydroxyl radicals is significantly
      prevented by RGP. It also modulates the levels of LPO and perceptibly increases
      the endogenous antioxidant enzymes level in DENA-induced hepatocellular
      carcinogenesis. The findings suggest that RGP prevents hepatocellular carcinoma
      by suppressing the marked increase in the levels of serum marker enzymes, and
      suppresses the free radical by scavenging hydroxyl radicals. 

PMID- 24026430
TI  - Comparison of mesiodistal tooth crown diameters and arch dimensions between
      modern Mongolians and Japanese.
AB  - The purposes of this study were to establish normative data for mesiodistal tooth
      crown diameters and arch dimensions in Mongolian adults and to compare them with
      those of Japanese adults. The study materials comprised dental casts of 100
      modern Mongolian and 100 Japanese subjects (50 males, 50 females for each) with
      Angle Class I normal occlusion. The mean ages were 20 years 8 months for the
      Mongolian subjects and 20 years 0 months for the Japanese subjects. On the dental
      casts, the mesiodistal tooth crown diameters (excluding wisdom teeth) and dental
      arch dimensions were measured. The following arch dimensions were measured: inter
      canine lingual, inter-premolar lingual, inter-molar lingual, inter-molar central,
      coronal arch length, basal arch length, and basal arch width. In the Mongolian
      samples, significant sex differences were noted, and most of the items were
      significantly larger in males than in females. Significant differences between
      the Mongolian and Japanese samples were mainly noted in the premolar and molar
      regions, rather than in the anterior region, and were significantly smaller in
      the Mongolian samples. In the Mongolian samples, the molar section widths and
      basal arch width and length were significantly larger in males and females
      compared with the Japanese samples. These results suggest that the tooth crown
      size and arch dimensions in the Mongolian samples differed from those in the
      Japanese samples, and that establishment of the clinical norm for Mongolian
      adults might be helpful in formulating treatment plans for Mongolian patients,
      given that these parameters are the basic tools for diagnosis.

PMID- 24026431
TI  - Green pigmentation on the palms and soles. Acral green pigmentation (eccrine
      chromhidrosis).

PMID- 24026426
TI  - Treatment of invasive fungal infections in cancer patients-updated
      recommendations of the Infectious Diseases Working Party (AGIHO) of the German
      Society of Hematology and Oncology (DGHO).
AB  - The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology
      and Oncology (DGHO) here presents its updated recommendations for the treatment
      of documented fungal infections. Invasive fungal infections are a main cause of
      morbidity and mortality in cancer patients undergoing intensive chemotherapy
      regimens. In recent years, new antifungal agents have been licensed, and agents
      already approved have been studied in new indications. The choice of the most
      appropriate antifungal treatment depends on the fungal species suspected or
      identified, the patient's risk factors (e.g., length and depth of neutropenia),
      and the expected side effects. This guideline reviews the clinical studies that
      served as a basis for the following recommendations. All recommendations
      including the levels of evidence are summarized in tables to give the reader
      rapid access to the information.

PMID- 24026432
TI  - OM-RCA-01, a novel humanized monoclonal antibody targeting fibroblast growth
      factor receptor 1, in renal cell carcinoma model.
AB  - Fibroblast growth factor (FGF) receptor 1 (FGFR1) is a potential therapeutic
      target for treatment of metastatic renal cell carcinoma (RCC). We investigated
      the preclinical activity of OM-RCA-01, a novel therapeutic humanized anti-FGFR1
      antibody in RCC. OM-RCA-01 has been shown to inhibit in vitro kinase activity of
      FGFR1 and has high affinity (Kd of 1.59 nM). In human renal carcinoma Caki-1
      FGFR1-expressing cells, OM-RCA-01 potently inhibited FGF-mediated signaling and
      proliferation. In vivo, the tumors in untreated mice or mice treated with non
      specific IgG continued their aggressive growth to reach the size of 2,000 cm3, at
      which point the mice were killed. In contrast, treatment with OM-RCA-01 not only
      significant arrested further growth of the tumors (P < 0.01) but also
      demonstrated differences in tumor volume compared with vehicle already on Day 13.
      A similar anti-tumor activity of OM-RCA-01 was observed when the antibody was
      given in low (1 mg/kg) or high (10 mg/kg) doses (P = 0.917). In Matrigel assay,
      OM-RCA-01 significantly inhibited FGF-induced endothelial cell migration,
      capillary-like tubular structure and mature vessels formation. Administration of
      10 mg/kg antibody for up to 35 days resulted in minimal body weight loss and no
      observations of gross toxicity were made. Collectively, the data obtained with OM
      RCA-01 are consistent with potent inhibition of FGFR1-signaling, angiogenesis,
      and tumor growth. OM-RCA-01 is being developed clinically as an intravenous
      therapy for the treatment of clear cell RCC.

PMID- 24026433
TI  - Nanoparticulate paclitaxel demonstrates antitumor activity in PC3 and Ace-1
      aggressive prostate cancer cell lines.
AB  - BACKGROUND: Paclitaxel is an effective antimitotic agent in cancer treatment;
      however, one of its most common toxicities is hypersensitivity due to excipients
      used for water solubility. Nanoparticulate paclitaxel (Crititax(r), CTI52010) is
      paclitaxel that consists only of nanoparticulate drug in saline. Our objective
      was to examine the effect of nanoparticulate paclitaxel on prostate cancer cells
      derived from castration-resistant prostate cancer in men and dogs, as companion
      dogs represent a unique naturally occurring model of castration-resistant
      prostate cancer. We hypothesized that nanoparticulate paclitaxel would be
      effective in affecting cell viability, colony forming ability, apoptosis, and
      induction of structural changes to the microtubules of prostate cancer cells.
      METHODS: Human PC3 and canine Ace-1 cells were treated with 0.001-1.0 MUm
      concentrations of paclitaxel and nanoparticulate paclitaxel. Cell viability,
      apoptosis, and colony forming assays were analyzed and compared in the presence
      of both drugs. Microtubule structure was examined by fluorescence microscopy
      following incubation with drug. RESULTS: Nanoparticulate paclitaxel was as
      effective as standard paclitaxel in decreasing cell viability, decreasing colony
      forming ability, and inducing apoptosis in human and canine prostate cancer cells
      in a dose-dependent manner. Fluorescence microscopy confirmed the microtubule
      target of nanoparticulate paclitaxel. CONCLUSIONS: Nanoparticulate paclitaxel is
      as effective as paclitaxel in decreasing cell viability, initiating apoptosis,
      decreasing cell survival, and causing rigidity of microtubules in both human and
      canine castration-resistant prostate cancer. This represents an attractive area
      for further study, using the companion dog as a model for disease in men.

PMID- 24026434
TI  - Clinical characteristics and outcomes of patients with grayanotoxin poisoning
      after the ingestion of mad honey from Nepal.
AB  - The aims of this study were to evaluate the clinical characteristics and outcomes
      of patients with grayanotoxin poisoning due to mad honey brought from Nepal.
      Medical records of patients with mad honey poisoning admitted to the emergency
      department between 1 January 2004 and 31 May 2012 were retrospectively reviewed.
      A total of 15 patients were included in this study. In all patients, mad honey
      was brought from the Himalayan region of Nepal. The mean age was 52.2 years, and
      66.7 % were men. The mean amount of mad honey ingested was 47 cc, and the mean
      time from ingestion to onset of symptoms was 36 min. In all patients, initial
      vital signs showed hypotension and bradycardia. The initial electrocardiogram
      showed sinus bradycardia in eight patients, junctional bradycardia in four
      patients, complete atrioventricular block in two patients, and atrial
      fibrillation with slow ventricular response in one patient. Four patients were
      treated with intravenous normal saline solution only. Eleven patients were
      treated with intravenous normal saline solution and intravenous atropine sulfate
      in a dose ranging from 0.5 to 2.0 mg. In all patients, the blood pressure and
      pulse rate returned to normal limits within 24 h. There were no deaths. The
      clinical characteristics and outcome of grayanotoxin poisonings caused by the
      ingestion of mad honey from Nepal are similar with those of mad honey from the
      Black Sea region of Turkey.

PMID- 24026435
TI  - Bioactive flavonoid p-hydroxycinnamic acid stimulates osteoblastogenesis and
      suppresses adipogenesis in bone marrow culture.
AB  - The bioactive flavonoid p-hydroxycinnamic acid (HCA), which is an intermediate
      metabolic substance in plants and fruits, is synthesized from tyrosine. The
      biological effect of HCA is poorly understood. Among cinnamic acid and its
      related compounds, HCA has a specific-anabolic effect on bone, being found to
      stimulate osteoblastogenesis and to inhibit osteoclastogenesis through the
      suppression of NF-kappaB signaling, thereby preventing bone loss. Bone marrow
      mesenchymal stem cells give rise to ostoblasts and adipocytes. HCA might
      therefore have effects on osteoblastogenesis and adipogenesis in bone marrow
      culture. This study demonstrates (1) that HCA has stimulatory effects on
      osteoblastogenesis and mineralization and suppressive effects on adipogenesis in
      mouse bone marrow culture and (2) that HCA depresses adipogenesis in mouse 3T3-L1
      preadipocytes in vitro. Such effects of HCA might be involved in the
      differentiation of mesenchymal stem cells. 

PMID- 24026436
TI  - Downregulation of gas5 increases pancreatic cancer cell proliferation by
      regulating CDK6.
AB  - Recent studies have revealed that long non-coding RNAs (lncRNAs) play important
      roles in cancer biology and that lncRNA gas5 (growth arrest-specific 5) regulates
      breast cancer cell growth. However, the role of gas5 in pancreatic cancer
      progression remains largely unknown. In the current study, we assay the
      expression level of gas5 in pancreatic cancer tissues and define the role of gas5
      in the regulation of pancreatic cancer cell proliferation. We verify that the
      expression level of gas5 is significantly decreased in pancreatic cancer tissues
      compared with normal control. Overexpression of gas5 in pancreatic cancer cells
      inhibits cell proliferation, whereas gas5 inhibition induces a significant
      decrease in G0/G1 phase and an increase in S phase. We further demonstrate that
      gas5 negatively regulates CDK6 (cyclin-dependent kinase 6) expression in vitro
      and in vivo. More importantly, knockdown of CDK6 partially abrogates gas5-siRNA
      induced cell proliferation. These data suggest an important role of gas5 in the
      molecular etiology of pancreatic cancer and implicate the potential application
      of gas5 in pancreatic cancer therapy. 

PMID- 24026437
TI  - Increasing cell plating density mimics an early post-LH stage in cultured bovine
      granulosa cells.
AB  - Cultured ovarian granulosa cells are essential models to study molecular
      mechanisms of gene regulation during folliculogenesis. Here, we characterize
      primary tissue culture models for bovine granulosa cells by morphological and
      physiological parameters and by novel molecular luteinization markers, as
      transcript abundance and DNA methylation levels. The data show that: (1) collagen
      substrate increased the number of attached, viable cells; (2) the expression of
      the key transcripts of estrogen synthesis, CYP19A1, could be induced and
      maintained in granulosa cells from small to medium but not from large follicles,
      whereas (3) only granulosa cells from large but not from smaller follicles were
      responsive to LH; (4) serum supplementation unfavorably transformed the cellular
      phenotype, induced proliferation and PCNA expression, reduced or abolished the
      transcript abundance of steroidogenic key genes and of gonadotropin receptor
      genes, CYP11A1, CYP19A1, FSHR and LHCGR but, however, did not increase the
      abundance of the luteinization-specific marker transcripts PTGS2, PTX3, RGS2 and
      VNN2; but (5) by increasing the plating density, estradiol production and the
      abundance of CYP19A1 transcripts, in particular those derived from the main
      ovarian promoter P2, were decreased concurrently leaving P2-specific DNA
      methylation levels unchanged, whereas progesterone secretion was stimulated and
      the expression of both luteinization-specific marker transcripts, RGS2 and VNN2,
      was significantly induced. From these data, we conclude that increasing the
      plating density induces a different, partly complementary, physiological and gene
      expression profile in cultured bovine granulosa cells and drives the cells
      towards an early post-LH stage of luteinization, even in the absence of
      luteinizing agents. 

PMID- 24026438
TI  - Three-dimensional studies of Prop1-expressing cells in the rat pituitary just
      before birth.
AB  - Recently, we demonstrated that differentiation was underway as early as embryonic
      day (E) 13.5 in the lateral region of the rat pituitary primordium. In this
      study, we analyze the heterogeneous property of cells in the pituitary at E21.5
      (just before birth) leading to its biological function with the differentiation
      and expansion of tissue. The three-dimensional structure of the pituitary at
      E21.5 was built up from measurements taken from many DAPI-stained sections and
      cell populations positive to the stem/progenitor marker SOX2, pituitary-specific
      transcription factor PROP1 and paired-related homeodomain transcription factor
      PRX. At E21.5, the pituitary, composed of anterior and intermediate lobes, showed
      a flattened chestnut shape with dimensions of about 500 MUm (dorsoventral axis)
      by 2500 MUm (left-right axis) by 850 MUm (rostrocaudal axis) and consisted in
      approximately 113,500, 16,000 and 14,800 cells in the anterior, intermediate and
      posterior lobes, respectively. Five cell types were observed expressing Sox2,
      Prop1 and Prx; these were heterogeneously distributed in the mediolateral and
      dorsoventral axes. In the anterior lobe, the marginal cell layer (MCL) was mostly
      occupied by stem/progenitor cells positive for SOX2, with the co-expression of
      Prop1 and/or Prx, whereas more SOX2-single-positive cells than those for PROP1
      and PRX were scattered in the parenchyma. PRX-positive cells of mesenchymal
      origin invaded the parenchyma, together with PECAM- and NESTIN-positive cells,
      indicating the advance of vasculogenesis. Thus, marked developmental progress
      occurs regarding the transition of stem/progenitor cells in the MCL and regarding
      vasculogenesis in the parenchyma during the prenatal pituitary growth wave.

PMID- 24026439
TI  - The tannosome is an organelle forming condensed tannins in the chlorophyllous
      organs of Tracheophyta.
AB  - BACKGROUND AND AIMS: Condensed tannins (also called proanthocyanidins) are
      widespread polymers of catechins and are essential for the defence mechanisms of
      vascular plants (Tracheophyta). A large body of evidence argues for the synthesis
      of monomeric epicatechin on the cytosolic face of the endoplasmic reticulum and
      its transport to the vacuole, although the site of its polymerization into
      tannins remains to be elucidated. The aim of the study was to re-examine the
      cellular frame of tannin polymerization in various representatives of the
      Tracheophyta. METHODS: Light microscopy epifluorescence, confocal microscopy,
      transmission electron microscopy (TEM), chemical analysis of tannins following
      cell fractionation, and immunocytochemistry were used as independent methods on
      tannin-rich samples from various organs from Cycadophyta, Ginkgophyta,
      Equisetophyta, Pteridophyta, Coniferophyta and Magnoliophyta. Tissues were fixed
      in a caffeine-glutaraldehyde mixture and examined by TEM. Other fresh samples
      were incubated with primary antibodies against proteins from both chloroplastic
      envelopes and a thylakoidal chlorophyll-carrying protein; they were also
      incubated with gelatin-Oregon Green, a fluorescent marker of condensed tannins.
      Coupled spectral analyses of chlorophyll and tannins were carried out by confocal
      microscopy on fresh tissues and tannin-rich accretions obtained through cell
      fractionation; chemical analyses of tannins and chlorophylls were also performed
      on the accretions. KEY RESULTS AND CONCLUSIONS: The presence of the three
      different chloroplast membranes inside vacuolar accretions that constitute the
      typical form of tannin storage in vascular plants was established in fresh
      tissues as well as in purified organelles, using several independent methods.
      Tannins are polymerized in a new chloroplast-derived organelle, the tannosome.
      These are formed by pearling of the thylakoids into 30 nm spheres, which are then
      encapsulated in a tannosome shuttle formed by budding from the chloroplast and
      bound by a membrane resulting from the fusion of both chloroplast envelopes. The
      shuttle conveys numerous tannosomes through the cytoplasm towards the vacuole in
      which it is then incorporated by invagination of the tonoplast. Finally, shuttles
      bound by a portion of tonoplast aggregate into tannin accretions which are stored
      in the vacuole. Polymerization of tannins occurs inside the tannosome regardless
      of the compartment being crossed. A complete sequence of events apparently valid
      in all studied Tracheophyta is described.

PMID- 24026440
TI  - Floral polymorphism in Chamaecrista flexuosa (Fabaceae-Caesalpinioideae): a
      possible case of atypical enantiostyly?
AB  - BACKGROUND AND AIMS: Reciprocal herkogamy, including enantiostyly and
      heterostyly, involves reciprocity in the relative positions of the sexual
      elements within the flower. Such systems result in morphologically and, since
      pollen is deposited on and captured from different parts of the pollinator,
      functionally distinct floral forms. Deviations from the basic pattern may modify
      the functionality of these mechanisms. For heterostylous species, such deviations
      are generally related to environmental disturbances, pollination services and/or
      reduced numbers of one floral morph. Deviations for enantiostylous species have
      not yet been reported. This study aims to investigate enantiostyly in
      Chamaecrista flexuosa, in particular the presence of deviations from the standard
      form, in an area of coastal vegetation in north-east Brazil. METHODS:
      Observations and investigations of floral biology, the reproductive system,
      pollinator behaviour, floral morphology and morphometry were performed. KEY
      RESULTS: In C. flexuosa flowers, anthers of different size but similar function
      are grouped. The flowers were self-compatible and set fruits after every
      treatment, except in the spontaneous self-pollination experiment, thereby
      indicating their dependence on pollen vectors. The flowers were pollinated by
      bees, especially Xylocopa cearensis and X. grisencens. Pollen is deposited and
      captured from the ventral portion of the pollinator's body. Variations in the
      spatial arrangement of floral elements allowed for the identification of floral
      morphs based on both morphological and functional criteria. Using morphological
      criteria, morphologically right (MR) and morphologically left (ML) floral morphs
      were identified. Three floral morphs were identified using functional criteria:
      functionally right (FR), functionally central (FC) and functionally left (FL).
      Combinations of morphologically and functionally defined morphs did not occur in
      equal proportions. There was a reduced frequency of the MR-FR combination.
      CONCLUSIONS: The results indicate the occurrence of an atypical enantiostyly in
      C. flexuosa. This seems to improve reproductive success by increasing the
      efficiency of pollen deposition and capture.

PMID- 24026441
TI  - Bis(oxalato)dioxovanadate(V) and bis(oxalato)oxoperoxo-vanadate(V) complexes:
      spectroscopic characterization and biological activity.
AB  - Two structurally related vanadium(V) complexes, K3[VO2(C2O4)2] . 3H2O and
      K3[VO(O2)(C2O4)2] . 1/2H2O, were thoroughly characterized by infrared, Raman, and
      electronic spectroscopies. The effect of both complexes on the viability of the
      human MG-63 osteosarcoma cells was tested using the MTT assay. The monoperoxo
      complex shows a very strong antiproliferative activity (at 100-MUM concentration,
      this complex diminished the cell viability ca. 80 %), whereas the dioxo complex
      was inactive.

PMID- 24026442
TI  - The effect of stress on salivary metal ion content in orthodontic patients.
AB  - Psychological stress can alter the environment in favor of corrosion of
      orthodontic alloys by changing the properties of saliva. This study aimed to
      assess the effect of stress induction on salivary nickel and chromium content in
      fixed orthodontic patients. Thirty patients were enrolled in this experiment.
      Saliva sample collection was performed at four time points: T1, before insertion
      of orthodontic appliances; T2, 3 months after the initiation of orthodontic
      treatment, before induction of stress; T3, 15 min following the induction of
      stress by Trier Social Stress Test; and T4, 30 min following the induction of
      stress. Ion content was measured by atomic absorption spectrophotometry. The
      obtained data were analyzed by repeated measures analysis of variance (ANOVA) and
      post hoc Bonferroni test. The mean amount of salivary nickel increased from 11.9
      +/- 5.1 MUg/L at T1 to 14.1 +/- 5.3 MUg/L at T4. This increase was found
      significant only at T4 comparing to T1. The average salivary chromium content
      changed from 4.1 +/- 2.3 MUg/L at T1 to 5.1 +/- 3.3 MUg/L at T4. None of the
      differences were significant for chromium. In conclusion, induction of stress in
      this study led to a significant increase in nickel release from orthodontic
      appliances into saliva. The salivary chromium content however was not
      significantly altered, yet gradually increased. 

PMID- 24026443
TI  - When a repellent becomes an attractant: harmful saponins are kairomones
      attracting the symbiotic Harlequin crab.
AB  - Marine organisms have developed a high diversity of chemical defences in order to
      avoid predators and parasites. In sea cucumbers, saponins function as repellents
      and many species produce these cytotoxic secondary metabolites. Nonetheless, they
      are colonized by numerous symbiotic organisms amongst which the Harlequin crab,
      Lissocarcinus orbicularis, is one of the most familiar in the Indo-Pacific Ocean.
      We here identify for the first time the nature of the molecules secreted by sea
      cucumbers and attracting the symbionts: saponins are the kairomones recognized by
      the crabs and insuring the symbiosis. The success of this symbiosis would be due
      to the ability that crabs showed during evolution to bypass the sea cucumber
      chemical defences, their repellents becoming powerful attractants. This study
      therefore highlights the complexity of chemical communication in the marine
      environment. 

PMID- 24026444
TI  - The role of solvent exclusion in the interaction between D124 and the metal site
      in SOD1: implications for ALS.
AB  - Structural changes in the metal site of the copper-zinc superoxide dismutase
      (SOD1) are involved in the various mechanisms proposed for the pathogenesis of
      the SOD1-linked familial form of amyotrophic lateral sclerosis (ALS). Elucidating
      how the metal site of SOD1 can be disrupted by ALS-linked mutations is important
      for a better understanding of the pathogenesis of the disease and for developing
      more efficient treatments. Residue D124, a second-sphere ligand of the copper and
      zinc ions, is known from experimental studies to be essential for the integrity
      of the metal-site structure. In this work, we used density functional theory
      calculations and molecular dynamics simulations to elucidate which factors keep
      D124 attached to the metal site and how structural changes may disrupt the
      binding between D124 and the metal first-sphere ligands. The calculations show
      that D124 is kept attached to the metal site in a kinetic trap. The exclusion of
      solvent molecules by the electrostatic loop of the protein is found to create the
      binding of D124 to the metal site. The calculations also indicate that changes in
      the structure of the electrostatic loop of the protein can weaken the D124-metal
      site interaction, lowering the affinity of the zinc site for the metal.
      Destabilization of the electrostatic loop of SOD1 has been previously shown to be
      a common property of ALS-linked variants of the protein, but its role in the
      pathogenesis of SOD1-linked ALS has not been elucidated. 

PMID- 24026446
TI  - Effect of storage temperature on the microbial composition of ready-to-use
      vegetables.
AB  - Four different salad preparations were investigated from microbiological point of
      view: two were packaged in air and two under Modified Atmosphere. The samples
      were stored at 4 and 10  degrees C, and analysed at established times. Total
      bacterial count (TBC) was taken as the most relevant index to define their
      hygiene and quality at both temperatures. Lactic acid bacteria, yeasts and moulds
      were found only occasionally. In general, the most important factor was the
      packaging technique: TBC was lower when the product is packed under modified
      conditions. The packaging technique also influences the microbial population:
      Gram-negative aerobic rods are dominant in air-packaged products, whilst the
      presence of Enterobacteriaceae becomes important in salads packaged under
      Modified Atmosphere. Pseudomonas fluorescens, with all its biovars, was the most
      frequently found species amongst the aerobic isolates, whilst for the
      Enterobacteriaceae strains, there was no dominant species. 

PMID- 24026447
TI  - Microarray chip based identification of a mixed infection of bovine herpesvirus 1
      and bovine viral diarrhea 2 from Indian cattle.
AB  - Bovine herpesvirus 1 (BHV1) and bovine viral diarrhea virus 2 (BVD2) are endemic
      in India although no mixed infection with these viruses has been reported from
      India. We report first mixed infection of these viruses in cattle during routine
      screening with a microarray chip. 62 of the 69 probes of BHV1 and 42 of the 57
      BVD2 probes in the chip gave positive signals for the virus. The virus infections
      were subsequently confirmed by RT-PCR. We also discuss the implications of these
      findings. 

PMID- 24026453
TI  - Skin bleaching as a dermatologic intervention: complicity or service?

PMID- 24026449
TI  - Comparison of methods for isolation of bacterial and fungal DNA from human blood.
AB  - The study aimed at optimization of DNA isolation from blood of representatives of
      four microbial groups causing sepsis, i.e., Gram negative: Escherichia coli, Gram
      positive: Staphylococcus aureus, yeast: Candida albicans, and filamentous fungus:
      Aspergillus fumigatus. Additionally, the five commercial kits for microbial DNA
      isolation from the blood were tested. The developed procedure of DNA isolation
      consisted of three consecutive steps, i.e., mechanical disruption, chemical
      lysis, and thermal lysis. Afterward, DNA was isolated from the previously
      prepared samples (erythrocyte lysis) with the use of five commercial kits for DNA
      isolation. They were compared paying heed to detection limit, concentration, DNA
      purity, and heme concentration in samples. The isolation of DNA without
      preliminary erythrocyte lysis resulted in far higher heme concentration than when
      lysis was applied. In the variant with erythrocyte lysis, two of the commercial
      kits were most effective in purifying the DNA extract from heme. Designed
      procedure allowed obtaining microbial DNA from all four groups of pathogens under
      study in the amount sufficient to conduct the rtPCR reaction, which aimed at
      detecting them in the blood. 

PMID- 24026454
TI  - Pharaonic trichology: the Ebers Papyrus.

PMID- 24026455
TI  - Remembering Louis Tribondeau (1872-1918).

PMID- 24026448
TI  - Viscera-associated bacterial diversity among intertidal gastropods from Northern
      Atlantic coast of Portugal.
AB  - Culture-dependent evaluation of the bacteria was carried out on gastropods, such
      as Monodonta lineata, Gibbula umbilicalis, Nucella lapillus and Patella
      intermedia, and the environmental samples (biofilm and surrounding sea water)
      collected from six different locations of Northern Portugal coastal area to
      investigate the interactions between the microbes in the viscera of gastropods
      and in the environment. A total of 141 isolates and 39 operational taxonomic
      units were identified. Phylogenetic analysis based on the 16S rRNA gene showed
      that bacterial isolates are highly diverse and most of them were found in other
      marine environment. The observed bacterial diversity was distributed over five
      different classes (Gammaproteobacteria, Alphaproteobacteria, Flavobacteria,
      Bacilli and Actinobacteria) with the greatest number of 16S rRNA gene sequence
      derived from the Gammaproteobacteria (77 %). Vibrio is found to be the dominant
      one among the different bacterial species isolated. The results suggest that the
      microorganisms in the environment are maintained in the viscera of the gastropods
      which may have a key role in the metabolic functions. 

PMID- 24026459
TI  - Favorite animal names in dermatology.

PMID- 24026460
TI  - Acetylpuerarin increases cell viability and reduces apoptosis in rat hippocampal
      neurons following oxygen-glucose deprivation/reperfusion.
AB  - The effects of acetylpuerarin treatment following oxygen-glucose
      deprivation/reperfusion (OGD/R) were examined in rat hippocampal neurons in vitro
      and compared with the effects of acetylpuerarin in normoxic cells to confirm
      acetylpuerarin's potential neuroprotective effects, including apoptosis
      inhibition. Wistar rat embryo hippocampal cells (day 18, E18) cultured for 8 days
      were subjected to 3 h OGD treatment, followed by reperfusion for 12, 24 or 36 h.
      For each time interval, a group of cells was left untreated (OGD/R-only groups)
      and treated with 0.1, 0.4 and 1.6 uM acetylpuerarin (OGD/R+acetylpuerarin).
      Neuron viability, apoptosis and caspase-8 and -3 activities were assessed by the
      reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT),
      4',6-diamidino-2-phenylindole (DAPI) and terminal deoxynucleotidyl-transferase
      mediated dUTP nick end labeling (TUNEL) and spectrophotometric assays,
      respectively. Fas-ligand (Fas-L), Fas-associated death domain (FADD) and tumor
      necrosis factor-alpha (TNF-alpha) were determined by western blot analysis.
      Compared with control cells, OCD/R+acetylpuerarin cells treated with 0.1, 0.4 and
      1.6 uM doses showed a concentration-dependent increase in hippocampal cell
      survival and viability by 69.93 +/- 2.28%, 81.49 +/- 2.13% and 85.28 +/- 2.38% at
      12 h, 68.59 +/- 3.02%, 77.85 +/- 2.84% and 85.64 +/- 4.39% at 24 h and 69.70 +/-
      1.70%, 77.21 +/- 3.21% and 83.90 +/- 2.12% at 36 h (P<0.05). Furthermore,
      OCD/R+acetylpuerarin cells exhibited a dose-dependent decrease in caspase-8 and 
      3 activation, TUNEL and DAPI-positive neurons and Fas-L, FADD and TNF-alpha
      expression. In conclusion, acetylpuerarin protects against OGD/R-induced neuronal
      apoptosis predominantly in the first 24 h following ischemia, which may be useful
      in mediating neuronal apoptosis in ischemic stroke patients.

PMID- 24026461
TI  - The push and pull for global polio eradication.

PMID- 24026462
TI  - Presidential addresses of the Royal Society of Tropical Medicine and Hygiene:
      1907-2013.
AB  - Presidents have been required to give an inaugural address on commencing office
      at the Royal Society of Tropical Medicine and Hygiene (RSTMH) since its
      foundation in 1907. All presidential addresses were identified, sourced and
      assembled into an annotated bibliography. The majority of presidential addresses
      have been published in Transactions of the Royal Society of Tropical Medicine and
      Hygiene. Unpublished and in some cases 'lost' contributions have now been sourced
      where possible and archived at the RSTMH. This unique, rich and rewarding archive
      provides a vista into the development of the RSTMH and the discipline of tropical
      medicine. The archive is freely available to all.

PMID- 24026463
TI  - Infectious diarrhoea in antiretroviral therapy-naive HIV/AIDS patients in Kenya.
AB  - BACKGROUND: Diarrhoea is a significant cause of morbidity and mortality in
      immunocompromised patients. The objectives of this study were to investigate the
      aetiological agents, risk factors and clinical features associated with diarrhoea
      in HIV/AIDS patients in Kenya. METHODS: Sociodemographic, epidemiological and
      clinical data were obtained for 164 HIV/AIDS patients (70 with and 94 without
      diarrhoea) recruited from Kenyatta National Hospital, Kenya. Stool samples were
      examined for enteric pathogens by microscopy and bacteriology. RESULTS:
      Intestinal protozoa and fungi were identified in 70% of patients, more frequently
      in those with diarrhoea (p<0.001). Helminths were detected in 25.6% of patients
      overall, and bacterial pathogens were identified in 51% of patients with
      diarrhoea. Polyparasitism was more common in patients with diarrhoea than those
      without (p<0.0001). Higher CD4(+) T-cell count (OR = 0.995, 95% CI 0.992-0.998)
      and water treatment (OR = 0.231, 95% CI 0.126-0.830) were associated with a lower
      risk of diarrhoea, while close contact with cows (OR = 3.200, 95% CI 1.26-8.13)
      or pigs (OR = 11.176, 95% CI 3.76-43.56) were associated with a higher risk of
      diarrhoea. CONCLUSIONS: Multiple enteric pathogens that are causative agents of
      diarrhoea were isolated from stools of antiretroviral therapy-naive HIV/AIDS
      patients, indicating a need for surveillance, treatment and promotion of hygienic
      practices.

PMID- 24026464
TI  - What to do about unsafe medicines?

PMID- 24026465
TI  - Descriptions of non-pharmacological interventions in clinical trials.

PMID- 24026466
TI  - High adherence to HIV prophylaxis reduces chances of infection from partner,
      research finds.

PMID- 24026467
TI  - Medical data: does patient privacy trump access for research?

PMID- 24026468
TI  - E-cigarette use doubles among US middle and high school students.

PMID- 24026469
TI  - Characterizations of particle size distribution of the droplets exhaled by
      sneeze.
AB  - This work focuses on the size distribution of sneeze droplets exhaled immediately
      at mouth. Twenty healthy subjects participated in the experiment and 44 sneezes
      were measured by using a laser particle size analyser. Two types of distributions
      are observed: unimodal and bimodal. For each sneeze, the droplets exhaled at
      different time in the sneeze duration have the same distribution characteristics
      with good time stability. The volume-based size distributions of sneeze droplets
      can be represented by a lognormal distribution function, and the relationship
      between the distribution parameters and the physiological characteristics of the
      subjects are studied by using linear regression analysis. The geometric mean of
      the droplet size of all the subjects is 360.1 um for unimodal distribution and
      74.4 um for bimodal distribution with geometric standard deviations of 1.5 and
      1.7, respectively. For the two peaks of the bimodal distribution, the geometric
      mean (the geometric standard deviation) is 386.2 um (1.8) for peak 1 and 72.0 um
      (1.5) for peak 2. The influences of the measurement method, the limitations of
      the instrument, the evaporation effects of the droplets, the differences of
      biological dynamic mechanism and characteristics between sneeze and other
      respiratory activities are also discussed.

PMID- 24026470
TI  - High fidelity information processing in folic acid chemotaxis of Dictyostelium
      amoebae.
AB  - Living cells depend upon the detection of chemical signals for their existence.
      Eukaryotic cells can sense a concentration difference as low as a few per cent
      across their bodies. This process was previously suggested to be limited by the
      receptor-ligand binding fluctuations. Here, we first determine the chemotaxis
      response of Dictyostelium cells to static folic acid gradients and show that they
      can significantly exceed this sensitivity, responding to gradients as shallow as
      0.2% across the cell body. Second, using a previously developed information
      theory framework, we compare the total information gained about the gradient
      (based on the cell response) to its upper limit: the information gained at the
      receptor-ligand binding step. We find that the model originally applied to cAMP
      sensing fails as demonstrated by the violation of the data processing inequality,
      i.e. the total information exceeds the information at the receptor-ligand binding
      step. We propose an extended model with multiple known receptor types and with
      cells allowed to perform several independent measurements of receptor occupancy.
      This does not violate the data processing inequality and implies the receptor
      ligand binding noise dominates both for low- and high-chemoattractant
      concentrations. We also speculate that the interplay between exploration and
      exploitation is used as a strategy for accurate sensing of otherwise unmeasurable
      levels of a chemoattractant. 

PMID- 24026471
TI  - From daily movements to population distributions: weather affects competitive
      ability in a guild of soaring birds.
AB  - The ability of many animals to access and exploit food is dependent on the
      ability to move. In the case of scavenging birds, which use soaring flight to
      locate and exploit ephemeral resources, the cost and speed of movement vary with
      meteorological factors. These factors are likely to modify the nature of
      interspecific interactions, as well as individual movement capacity, although the
      former are less well understood. We used aeronautical models to examine how
      soaring performance varies with weather within a guild of scavenging birds and
      the consequences this has for access to a common resource. Birds could be divided
      broadly into those with low wing loading that are more competitive in conditions
      with weak updraughts and low winds (black vultures and caracaras), and those with
      high wing loading that are well adapted for soaring in strong updraughts and
      moderate to high winds (Andean condors). Spatial trends in meteorological factors
      seem to confine scavengers with high wing loading to the mountains where they out
      compete other birds; a trend that is borne out in worldwide distributions of the
      largest species. However, model predictions and carcass observations suggest that
      the competitive ability of these and other birds varies with meteorological
      conditions in areas where distributions overlap. This challenges the view that
      scavenging guilds are structured by fixed patterns of dominance and suggests that
      competitive ability varies across spatial and temporal scales, which may
      ultimately be a mechanism promoting diversity among aerial scavengers. 

PMID- 24026472
TI  - Characterizing the dynamics of rubella relative to measles: the role of
      stochasticity.
AB  - Rubella is a completely immunizing and mild infection in children. Understanding
      its behaviour is of considerable public health importance because of congenital
      rubella syndrome, which results from infection with rubella during early
      pregnancy and may entail a variety of birth defects. The recurrent dynamics of
      rubella are relatively poorly resolved, and appear to show considerable diversity
      globally. Here, we investigate the behaviour of a stochastic seasonally forced
      susceptible-infected-recovered model to characterize the determinants of these
      dynamics and illustrate patterns by comparison with measles. We perform a
      systematic analysis of spectra of stochastic fluctuations around stable
      attractors of the corresponding deterministic model and compare them with spectra
      from full stochastic simulations in large populations. This approach allows us to
      quantify the effects of demographic stochasticity and to give a coherent picture
      of measles and rubella dynamics, explaining essential differences in the
      recurrent patterns exhibited by these diseases. We discuss the implications of
      our findings in the context of vaccination and changing birth rates as well as
      the persistence of these two childhood infections. 

PMID- 24026473
TI  - Modelling the spread of American foulbrood in honeybees.
AB  - We investigate the spread of American foulbrood (AFB), a disease caused by the
      bacterium Paenibacillus larvae, that affects bees and can be extremely damaging
      to beehives. Our dataset comes from an inspection period carried out during an
      AFB epidemic of honeybee colonies on the island of Jersey during the summer of
      2010. The data include the number of hives of honeybees, location and owner of
      honeybee apiaries across the island. We use a spatial SIR model with an
      underlying owner network to simulate the epidemic and characterize the epidemic
      using a Markov chain Monte Carlo (MCMC) scheme to determine model parameters and
      infection times (including undetected 'occult' infections). Likely methods of
      infection spread can be inferred from the analysis, with both distance- and owner
      based transmissions being found to contribute to the spread of AFB. The results
      of the MCMC are corroborated by simulating the epidemic using a stochastic SIR
      model, resulting in aggregate levels of infection that are comparable to the
      data. We use this stochastic SIR model to simulate the impact of different
      control strategies on controlling the epidemic. It is found that earlier
      inspections result in smaller epidemics and a higher likelihood of AFB
      extinction. 

PMID- 24026474
TI  - Modelling the perennial energy crop market: the role of spatial diffusion.
AB  - Biomass produced from energy crops, such as Miscanthus and short rotation coppice
      is expected to contribute to renewable energy targets, but the slower than
      anticipated development of the UK market implies the need for greater
      understanding of the factors that govern adoption. Here, we apply an agent-based
      model of the UK perennial energy crop market, including the contingent
      interaction of supply and demand, to understand the spatial and temporal dynamics
      of energy crop adoption. Results indicate that perennial energy crop supply will
      be between six and nine times lower than previously published, because of time
      lags in adoption arising from a spatial diffusion process. The model simulates
      time lags of at least 20 years, which is supported empirically by the analogue of
      oilseed rape adoption in the UK from the 1970s. This implies the need to account
      for time lags arising from spatial diffusion in evaluating land-use change,
      climate change (mitigation or adaptation) or the adoption of novel technologies. 

PMID- 24026475
TI  - Success factors for avian influenza vaccine use in poultry and potential impact
      at the wild bird-agricultural interface.
AB  - Thirty-two epizootics of high pathogenicity avian influenza (HPAI) have been
      reported in poultry and other birds since 1959. The ongoing H5N1 HPAI epizootic
      that began in 1996 has also spilled over to infect wild birds. Traditional
      stamping-out programs in poultry have resulted in eradication of most HPAI
      epizootics. However, vaccination of poultry was added as a control tool in 1995
      and has been used during five epizootics. Over 113 billion doses of AI vaccine
      have been used in poultry from 2002 to 2010 as oil-emulsified, inactivated whole
      AIV vaccines (95.5%) and live vectored vaccines (4.5%). Over 99% of the vaccine
      has been used in the four H5N1 HPAI enzootic countries: China including Hong Kong
      (91%), Egypt (4.7%), Indonesia (2.3%), and Vietnam (1.4%) where vaccination
      programs have been nationwide and routine to all poultry. Ten other countries
      used vaccine in poultry in a focused, risk-based manner but this accounted for
      less than 1% of the vaccine used. Most vaccine "failures" have resulted from
      problems in the vaccination process; i.e., failure to adequately administer the
      vaccine to at-risk poultry resulting in lack of population immunity, while fewer
      failures have resulted from antigenic drift of field viruses away from the
      vaccine viruses. It is currently not feasible to vaccinate wild birds against
      H5N1 HPAI, but naturally occurring infections with H5 low pathogenicity avian
      influenza viruses may generate cross-protective immunity against H5N1 HPAI. The
      most feasible method to prevent and control H5N1 HPAI in wild birds is through
      control of the disease in poultry with use of vaccine to reduce environmental
      burden of H5N1 HPAIV, and eventual eradication of the virus in domestic poultry,
      especially in domestic ducks which are raised in enzootic countries on range or
      in other outdoor systems having contact with wild aquatic and periurban
      terrestrial birds. 

PMID- 24026476
TI  - Fibroblast growth factor-7 facilitates osteogenic differentiation of embryonic
      stem cells through the activation of ERK/Runx2 signaling.
AB  - Fibroblast growth factor-7 (FGF7) is known to regulate proliferation and
      differentiation of cells; however, little information is available on how FGF7
      affects the differentiation of embryonic stem cells (ESCs). We examined the
      effects of FGF7 on proliferation and osteogenic differentiation of mouse ESCs.
      Exogenous FGF7 addition did not change the proliferation rate of mouse ESCs. In
      contrast, the addition of FGF7 facilitated the dexamethasone, ascorbic acid, and
      beta-glycerophosphate (DAG)-induced increases in bone-like nodule formation and
      calcium accumulation. FGF7 also augmented mRNA expression of runt-related
      transcription factor-2 (Runx2), osterix, bone sialoprotein (BSP), and osteocalcin
      (OC) in the presence of DAG. FGF7-mediated increases in the mineralization and
      bone-specific gene expression were almost completely attenuated by pretreating
      with anti-FGF7 antibody. FGF7 treatment accelerated the DAG-induced activation of
      extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in
      the cells. A pharmacological inhibitor specific to ERK, but not to JNK or p38
      kinase, dramatically suppressed FGF7-mediated mineralization and accumulation of
      collagen and OC in the presence of DAG. This suppression was accompanied by the
      reduction in Runx2, osterix, BSP, and OC mRNA levels, which were increased by
      FGF7 in the presence of DAG. Collectively, our results suggest that FGF7
      stimulates osteogenic differentiation, but not proliferation, in ESCs, by
      activating ERK/Runx2 signaling. 

PMID- 24026477
TI  - Ultrasound microbubbles combined with the NFkappaB binding motif increase
      transfection efficiency by enhancing the cytoplasmic and nuclear import of
      plasmid DNA.
AB  - Inefficient gene delivery poses a challenge for non-viral gene therapy.
      Cytoplasmic and nuclear membrane barriers are responsible for the inefficiency as
      they restrict the import of exogenous genes. The present study aimed to improve
      the transfection efficiency using a novel gene delivery system, which consisted
      of two components: ultrasound microbubbles and the nuclear factor kappaB
      (NFkappaB) binding motif. Ultrasound-targeted microbubble destruction (UTMD) was
      used to enhance the cytoplasmic import of plasmids and the NFkappaB binding motif
      was added to promote the nuclear intake of the plasmid from the cytoplasm. In the
      present study, human umbilical vein endothelial cells were transfected using UTMD
      with two different Cy3-labeled plasmids, phSDF-1alpha and phSDF-1alpha-NFkappaB.
      phSDF-1alpha-NFkappaB was constructed by inserting a specific DNA targeting
      sequence (five optimal repeats of the binding motif for the inducible
      transcription factor NFkappaB) into phSDF-1alpha. The nuclear import and gene
      expression efficiency of phSDF-1alpha-NFkappaB were compared with those of phSDF
      1alpha to investigate the effect of the NFkappaB binding motif on transfection.
      The results showed that UTMD significantly increased the cytoplasmic intake of
      pDNA and maintained high cell viability. The nuclear import and gene expression
      of phSDF-1alpha-NFkappaB-transfected cells were significantly higher than those
      transfected with phSDF-1alpha. Compared with the NFkappaB-free plasmids, the
      quantity of NFkappaB plasmids in the nucleus increased 6.5-fold and the
      expression of SDF-1alpha was 4.4-fold greater. These results suggest that UTMD
      combined with NFkappaB binding motif significantly improve transfection
      efficiency by enhancing the cytoplasmic and nuclear import of exogenous plasmid
      DNA.

PMID- 24026478
TI  - Stress myocardial perfusion imaging for the evaluation and triage of chest pain
      in the emergency department: a randomized controlled trial.
AB  - BACKGROUND: Patients with acute coronary syndrome (ACS) often present atypically.
      In a randomized controlled trial, we studied whether adding stress myocardial
      perfusion imaging (SMPI) to an evaluation strategy for emergency department (ED)
      patients presenting with chest pain more effectively identifies patients with
      ACS. METHODS: Participants were randomized to standard ED chest pain protocol
      (clinical assessment) or standard protocol supplemented with SMPI results. During
      6 hours of electrocardiogram (ECG) monitoring and serial cardiac markers
      (creatine kinase-MB isoenzyme, troponin), participants developing ST segment
      changes or elevated cardiac markers were admitted. Those with a negative
      observation period underwent SMPI (N = 1,004) or clinical assessment (N = 504)
      based on randomization, and admitted if their SMPI scan was abnormal or senior
      clinicians found a high or intermediate risk for ACS. RESULTS: SMPI participants
      had a significantly lower admission rate than clinical assessment participants
      (10.16% vs 18.45%), with no significant between-group differences in risk of
      cardiac events (CEs) after 30 days (0.40% vs 0.79%) or 1 year (0.70% vs 0.99%).
      CONCLUSIONS: When added to a standard triage strategy incorporating clinical
      evaluation, serial ECGs, and cardiac markers, SMPI improved clinical decision
      making for chest pain patients, significantly reducing the need for
      hospitalization without an increase in adverse CE rates at 30 days or 1 year.

PMID- 24026481
TI  - Dermatologic relationships between the United States and German-speaking
      countries: part 3--the Europeans come to the United States.
AB  - Following World War II, dermatology in German-speaking Europe faced enormous
      challenges, including the need to rebuild damaged or destroyed facilities, the
      replacement of the loss of many prewar leaders, and a raging venereal disease
      epidemic. Restoration of academic excellence and leadership required that young
      German-speaking dermatologists had to seek additional training in the United
      States, thereby reversing the historical trends of the 19th and early 20th
      centuries. Some of the initial visitors included Herbert Goldschmidt, Egon
      Macher, Gerd Steigleder, and Klaus Wolff. By the 1970s, there were numerous
      German-speaking scholars coming to the University of Pennsylvania, Philadelphia,
      with Albert Kligman and then to the Dermatology Branch at the National Institutes
      of Health and the Mayo Clinic, Rochester, Minnesota, and subsequently many other
      centers. Today, most of the leaders of German-speaking departments of dermatology
      have had some training in the United States. 

PMID- 24026479
TI  - Hybrid myocardial imaging for risk stratification prior to kidney
      transplantation: added value of coronary calcium and epicardial adipose tissue.
AB  - BACKGROUND: Patient selection and optimal approach to risk stratification prior
      to kidney transplantation remain uncertain. We sought new predictors of an
      abnormal myocardial perfusion (MYP) stress test result. METHODS: Retrospective
      study of 411 consecutive chronic kidney disease stages 4-5D patients awaiting
      kidney transplantation referred for risk stratification. PET-CT or SPECT-CT was
      used to assess MYP and quantify coronary artery calcium (CAC) and epicardial
      adipose tissue (EAT). Abnormal MYP was defined as a perfusion defect involving
      >=5% of the left ventricular myocardium. RESULTS: Fixed or reversible MYP defects
      were present in 41 patients (10%). Male sex, smoking, and history of
      cardiovascular disease were more prevalent; age was higher and CAC and EAT were
      greater in patients with MYP defects than in those with normal MYP. On
      multivariate logistic regression, EAT and CAC were independent predictors of
      abnormal MYP while diabetes mellitus showed a borderline association (P = .08).
      EAT added incremental diagnostic value to a model including age, CAC and diabetes
      mellitus [AUC 0.73 (95% CI 0.64-0.81) to 0.76 (95% CI 0.68-0.84; P = .02)].
      Furthermore, the model containing EAT showed improved diagnostic discrimination.
      CONCLUSIONS: Abnormal MYP on screening stress testing appears to be rare in
      patients awaiting kidney transplantation suggesting an excess of testing. EAT and
      CAC may help predict what patients are at higher risk of developing abnormalities
      of MYP under stress.

PMID- 24026483
TI  - Non-purged voltammetry explored with AGNES.
AB  - The reduction of oxygen increases pH in the surroundings of an electrode. A
      theoretical model estimates the steady-state pH profile from the surface of the
      electrode up to the bulk solution. A very simple formula predicts that, in non
      deaerated solutions, for bulk pH-values between 4.0 and 10.0, the corresponding
      surface pH could be as high as 10.3, regardless of the thickness of the diffusion
      layer and composition of the sample (except if it has a buffering capacity). For
      bulk pH lower than 3.0 or higher than 10, pH increases are negligible. Less steep
      pH-profiles are obtained using buffers (such as MOPS 0.01 M or MES 0.01 M). The
      change in surface pH modifies the local speciation and hinders the standard
      interpretation of voltammetric responses. The electroanalytical technique Absence
      of Gradients and Nernstian Equilibrium Stripping (AGNES), implemented with Screen
      Printed Electrodes (SPE), provides experimental insights into this phenomenon.
      AGNES probes the free metal concentration at the electrode surface, from which
      the surface pH can be estimated for systems of known composition. These
      estimations agree with the theoretical model for the assayed systems.
      Additionally, the quantification of the bulk free Zn(2+) and Cd(2+)
      concentrations with specific modifications of AGNES for non-purged synthetic
      solutions is discussed. In general, more accurate determinations of the bulk free
      metal concentrations in non-purged solutions are expected: (i) when the
      calibration is performed in a medium where the pH increase induces similar
      changes in the surface free metal concentration and in the sample solution and
      (ii) when the system is more buffered. 

PMID- 24026482
TI  - Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G2
      delay and mitotic defects.
AB  - The development of clinically useful histone deacetylase inhibitors has expanded
      greatly. In a preclinical study, we showed that panobinostat (LBH589) inhibits
      cell cycle progression of human head and neck squamous cell carcinoma (HNSCC)
      cell lines at G2/M and an associated decrease in expression of particular genes
      required for passage through G2 and mitosis. In this study we sought to analyse
      the mechanistic underpinnings of panobinostat-induced growth arrest. HNSCC cell
      lines were synchronised and progression through mitosis monitored. We demonstrate
      that panobinostat causes a marked G2 delay and mitotic defects. A loss of G2
      specific Plk1 and Cyclin B1 expression and co-incident increase in p21(Waf1/Cip1)
      expression is also shown. Furthermore, we show a significant loss of E2F1
      recruitment to the promoters of these genes in response to panobinostat
      treatment. These data provide mechanistic evidence of panobinostat-induced cell
      cycle arrest and highlight its potential as a chemotherapeutic agent for HNSCC.

PMID- 24026484
TI  - Pavlovian conditioned approach, extinction, and spontaneous recovery to an
      audiovisual cue paired with an intravenous heroin infusion.
AB  - RATIONALE: Novel stimuli paired with exposure to addictive drugs can elicit
      approach through Pavlovian learning. While such approach behavior, or sign
      tracking, has been documented for cocaine and alcohol, it has not been shown to
      occur with opiate drugs like heroin. Most Pavlovian conditioned approach
      paradigms use an operandum as the sign, so that sign tracking can be easily
      automated. OBJECTIVES: We were interested in assessing whether approach behavior
      occurs to an audiovisual cue paired with an intravenous heroin infusion. If so,
      would this behavior exhibit characteristics of other Pavlovian conditioned
      behaviors, such as extinction and spontaneous recovery? METHODS: Rats were
      repeatedly exposed to an audiovisual cue, similar to that used in standard self
      administration models, along with an intravenous heroin infusion. Sign tracking
      was measured in an automated fashion by analyzing motion pixels within the cue
      zone during each cue presentation. RESULTS: We were able to observe significant
      sign tracking after only five pairings of the conditioned stimulus (CS) with the
      unconditioned stimulus (US). This behavior rapidly extinguished over 2 days, but
      exhibited pronounced spontaneous recovery 3 weeks later. CONCLUSIONS: We conclude
      that sign tracking measured by these methods exhibits all the characteristics of
      a classically conditioned behavior. This model can be used to examine the
      Pavlovian component of drug memories, alone, or in combination with self
      administration methods.

PMID- 24026499
TI  - Vulnerability and diet breadth predict larval and adult parasite diversity in
      fish of the Bothnian Bay.
AB  - Recent studies of aquatic food webs show that parasite diversity is concentrated
      in nodes that likely favour transmission. Various aspects of parasite diversity
      have been observed to be correlated with the trophic level, size, diet breadth,
      and vulnerability to predation of hosts. However, no study has attempted to
      distinguish among all four correlates, which may have differential importance for
      trophically transmitted parasites occurring as larvae or adults. We searched for
      factors that best predict the diversity of larval and adult endoparasites in 4105
      fish in 25 species studied over a three-year period in the Bothnian Bay, Finland.
      Local predator-prey relationships were determined from stomach contents,
      parasites, and published data in 8,229 fish in 31 species and in seals and
      piscivorous birds. Fish that consumed more species of prey had more diverse
      trophically transmitted adult parasites. Larval parasite diversity increased with
      the diversity of both prey and predators, but increases in predator diversity had
      a greater effect. Prey diversity was more strongly associated with the diversity
      of adult parasites than with that of larvae. The proportion of parasite species
      present as larvae in a host species was correlated with the diversity of its
      predators. There was a notable lack of association with the diversity of any
      parasite guild and fish length, trophic level, or trophic category. Thus,
      diversity is associated with different nodal properties in larval and adult
      parasites, and association strengths also differ, strongly reflecting the life
      cycles of parasites and the food chains they follow to complete transmission. 

PMID- 24026500
TI  - The sensitivity of wood production to seasonal and interannual variations in
      climate in a lowland Amazonian rainforest.
AB  - Understanding climatic controls on tropical forest productivity is key to
      developing more reliable models for predicting how tropical biomes may respond to
      climate change. Currently there is no consensus on which factors control seasonal
      changes in tropical forest tree growth. This study reports the first
      comprehensive plot-level description of the seasonality of growth in a Peruvian
      tropical forest. We test whether seasonal and interannual variations in climate
      are correlated with changes in biomass increment, and whether such relationships
      differ among trees with different functional traits. We found that biomass
      increments, measured every 3 months on the two plots, were reduced by between 40
      and 55% in the peak dry season (July-September) relative to peak wet season
      (January-March). The seasonal patterns of biomass accumulation are significantly
      (p < 0.01) associated with seasonal patterns of rainfall and soil water content;
      however, this may reflect a synchrony of seasonal cycles rather than direct
      physiological controls on tree growth rates. The strength of the growth
      seasonality response among trees is significantly correlated to functional
      traits: consistent with a hypothesised trade-off between maximum potential growth
      rate and hydraulic safety, tall and fast-growing trees with broad stems had the
      most strongly seasonal biomass accumulation, suggesting that they are more
      productive in the wet season, but more vulnerable to water limitation in the dry
      season.

PMID- 24026501
TI  - Understanding the elevated risk of substance use by adolescents in special
      education and residential youth care: the role of individual, family and peer
      factors.
AB  - Adolescents who attend special education for behavioural problems (SEB) and
      adolescents who live in a residential youth care institution (RYC) are
      characterised by behavioural disorders and problematic family backgrounds and
      have an increased risk for substance use. Though it is likely that the high rates
      of substance use in SEB/RYC settings might be inherent to the risk profile of
      these adolescents, little is known about the actual role the risk profile has in
      explaining substance use. The present study examined the extent to which the
      elevated risk of substance use in SEB/RYC can be explained by high levels of
      individual, family, and peer risk indicators that are known to characterise their
      risk profile. Self-report questionnaires from 531 adolescents in RYC (50 % male;
      mean age 14.7) and 603 adolescents in SEB (81 % male; mean age 14.1) were
      compared with information from 1,905 adolescents attending special education for
      students with learning disabilities (SEL) (56 % male; mean age 14.1). Results
      show that adolescents in SEB/RYC reported higher levels of daily smoking, weekly
      alcohol consumption, cannabis and hard drug use, as well as greater prevalence of
      individual, family and peer factors. Though individual, family and in particular
      peer risk indicators all explain some of the variance in substance use, the
      differences between adolescents in SEB/RYC compared with SEL remained significant
      and substantial, with the exception of heavy alcohol consumption. These findings
      suggest that deviant peer affiliation, in particular, plays a role in explaining
      high substance use levels in SEB/RYC and those factors relevant to the
      residential settings and special education schools might also contribute to
      substance use in these high-risk groups.

PMID- 24026502
TI  - Engagement in HIV care among HIV-positive men who have sex with men from 21
      cities in the United States.
AB  - We assessed factors associated with HIV care among HIV-infected men who have sex
      with men (MSM). We used 2008 data on MSM from the National HIV Behavioral
      Surveillance System (NHBS). Venue-based, time-space sampling was used to recruit
      and interview men in 21 U.S. cities with high AIDS prevalence. Among self
      reported HIV-positive MSM, we used generalized estimating equations (clustered on
      city of interview) to evaluate factors associated with delayed linkage to care
      (care entry >3 months after diagnosis), not currently receiving care (no visit
      for HIV care during the 6 months before the study interview), and not being on
      antiretroviral therapy (ART). Among 8,153 MSM, 882 (11 %) were self-reported HIV
      positive. 25 % had delayed linkage, 12 % were not currently receiving care and
      among those with at least one heath care visit 30 % were not on ART. In
      multivariate analysis, lower income and testing positive at their first HIV test
      were associated with delayed linkage. Age 18-29 years, and not having health
      insurance were associated with not currently receiving care. Among those with at
      least one health care visit, being age 18-39 years, having private or no health
      insurance, and stimulant use were associated with not being on ART. These
      findings can inform efforts to improve engagement in care. 

PMID- 24026503
TI  - A third mitochondrial RNA polymerase in the moss Physcomitrella patens.
AB  - In most organisms, the mitochondrial genes are transcribed by RNA polymerases
      related to the single-subunit RNA polymerases of bacteriophages like T3 and T7.
      In flowering plants, duplication(s) of the RpoTm gene coding for the
      mitochondrial RNA polymerase (RPOTm) led to the evolution of additional RNA
      polymerases transcribing genes in plastids (RPOTp) or in both mitochondria and
      plastids (RPOTmp). Two putative RPOTmp enzymes were previously described to be
      encoded by the nuclear genes RpoTmp1 and RpoTmp2 in the moss Physcomitrella
      patens. Here, we report on a third Physcomitrella RpoT gene. We determined the
      sequence of the cDNA. Comparison of the deduced amino acid sequence with
      sequences of plant organellar RNA polymerases suggests that this gene encodes a
      functional phage-type RNA polymerase. The 78 N-terminal amino acids of the
      putative RNA polymerase were fused to GFP and found to target the fusion protein
      exclusively to mitochondria in Arabidopsis protoplasts. P. patens is the only
      known organism to possess three mitochondrial RNA polymerases.

PMID- 24026506
TI  - Augmenting obsessive-compulsive disorder treatment: from brain to mind.

PMID- 24026504
TI  - Rapid, efficient and precise allele replacement in the fission yeast
      Schizosaccharomyces pombe.
AB  - Gene targeting provides a powerful tool to modify endogenous loci to contain
      specific mutations, insertions and deletions. Precise allele replacement, with no
      other chromosomal changes (e.g., insertion of selectable markers or heterologous
      promoters), maintains physiologically relevant context. Established methods for
      precise allele replacement in fission yeast employ two successive rounds of
      transformation and homologous recombination and require genotyping at each step.
      The relative efficiency of homologous recombination is low and a high rate of
      false positives during the second round of gene targeting further complicates
      matters. We report that pop-in, pop-out allele replacement circumvents these
      problems. We present data for 39 different allele replacements, involving simple
      and complex modifications at seven different target loci, that illustrate the
      power and utility of the approach. We also developed and validated a rapid,
      efficient process for precise allele replacement that requires only one round
      each of transformation and genotyping. We show that this process can be applied
      in population scale to an individual target locus, without genotyping, to
      identify clones with an altered phenotype (targeted forward genetics). It is
      therefore suitable for saturating, in situ, locus-specific mutation screens
      (e.g., of essential or non-essential genes and regulatory DNA elements) within
      normal chromosomal context. 

PMID- 24026505
TI  - Antibiotic-impregnated cement spacer as a definitive treatment for post
      arthroscopy shoulder destructive osteomyelitis: case report and review of
      literature.
AB  - Arthroscopic revision of rotator cuff lesions is an increasingly popular
      procedure with a relatively safe profile. However, associated deep articular
      infection has been described, with potentially destructive joint sequelae. When
      occurring, it poses the double challenge of eradicating the infectious agent
      while preserving the articulation and its function. Experience remains scarce and
      is mostly based on case reports and small series. These also rely on the evidence
      from the better-described lower extremity joint infections. Through a complex
      case, the following report addresses this exceptional situation and offers an
      unusual solution, taking into consideration the peculiarities of the shoulder
      joint. With the consent of the patient, a single-stage resection arthroplasty
      with the implantation of an antibiotic-impregnated cement spacer was performed as
      a long-lasting-if not definite-treatment. After 4 years, the patient maintains
      excellent function with no radiological signs of wear or loosening. 

PMID- 24026507
TI  - A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus
      in a Turkish family.
AB  - X-linked nephrogenic diabetes insipidus (NDI) is a rare hereditary disease caused
      by mutations in arginine vasopressin type 2 receptor (AVPR2) and characterized by
      the production of large amounts of urine and an inability to concentrate urine in
      response to the antidiuretic hormone vasopressin. We have identified a novel 388
      bp deletion starting in intron 1 and ending in exon 2 in the AVPR2 gene in a
      patient with NDI and in his family. We have revealed that this mutation is a de
      novo mutation for the mother of the proband patient. Prospective clinical data
      were collected for all family members. The water deprivation test confirmed the
      diagnosis of diabetes insipidus. The patient has severe symptoms like deep
      polyuria nocturia, polydipsia, and fatigue. He was given arginine vasopressin
      treatment while he was a child. However, he could not get well due to his
      nephrogenic type of illness. Both of his nephews have the same complains in
      addition to failure to grow. We have sequenced all exons and intron-exon
      boundaries of the AVPR2 gene of all family members. The analyses of
      bioinformatics and comparative genomics of the deletion were done via considering
      the DNA level damage. AVPR2 gene mutation results in the absence of the three
      transmembrane domains, two extracellular domains, and one cytoplasmic domain.
      Three-dimensional protein structure prediction was shown. We concluded that X
      linked NDI and severity of illness in this family is caused by a novel 388 bp
      deletion in the AVPR2 gene that is predicted to truncate the receptor protein,
      and also this deletion may lead to dysfunctioning in protein activity and
      inefficient or inadequate binding abilities.

PMID- 24026508
TI  - Efficient synthesis of 4-oxo-4,5-dihydrothieno[3,2-c]quinoline-2-carboxylic acid
      derivatives from aniline.
AB  - The first reported synthesis of potential kinase inhibitors, 4-oxo-4,5
      dihydrothieno[3,2-c]quinoline-2-carboxylic acid derivatives starting from aniline
      is described. This efficient high yielding sequence was carried out in six steps
      without any chromatographic purification. A tandem nucleophilic aromatic
      substitution/cyclization reaction was used as a key step in the sequence. The
      versatile intermediate 2-carboxylic acid was used as a suitable precursor to
      access the functionalization of the C-ring, by convergent analog synthesis of
      several novel derivatives.

PMID- 24026510
TI  - Multi-petal cyclamen flowers produced by AGAMOUS chimeric repressor expression.
AB  - Cyclamen persicum (cyclamen) is a commercially valuable, winter-blooming
      perennial plant. We cloned two cyclamen orthologues of AGAMOUS (AG), CpAG1 and
      CpAG2, which are mainly expressed in the stamen and carpel, respectively.
      Cyclamen flowers have 5 petals, but expression of a chimeric repressor of CpAG1
      (CpAG1-SRDX) caused stamens to convert into petals, resulting in a flower with 10
      petals. By contrast, CpAG2-SRDX only caused incomplete formation of stamens and
      carpels. Expression in Arabidopsis thaliana showed similar effects on flower
      organ specification. Simultaneous expression of CpAG1-SRDX and CpAG2-SRDX in
      cyclamen induced rose-like, multi-petal flowers, a potentially valuable trait in
      commercial ornamental varieties. Expression of CpAG2-SRDX in a cyclamen mutant
      lacking expression of CpAG1 more effectively produced multi-petal flowers. Here,
      we controlled the number of petals in cyclamen by simple genetic engineering with
      a chimeric repressor. This strategy may be applicable useful for other ornamental
      plants with two distinct AG orthologues. 

PMID- 24026511
TI  - Aflatoxin M1 contamination in commercial pasteurized milk from local markets in
      Fariman, Iran.
AB  - Contamination of milk and dairy products with aflatoxin M1 (AFM1) presents a risk
      for human health. The aim of this study was to investigate the presence of AFM1
      in pasteurized milk samples in Fariman, located in the province of Khorasan
      Razavi, Iran, by enzyme-linked immunosorbent assay (ELISA). Forty-five samples of
      pasteurized milk from different supermarkets were collected during 3 months in
      summer (July to September, 2012). AFM1 contamination was detected in all of milk
      samples. The mean concentration of aflatoxin M1 was 27.2 ng/l. The range of AFM1
      content was 8.8-64 ng/l. Thirteen (28.8 %) of the samples had AFM1 levels
      exceeding the maximum levels (50 ng/l) accepted by the European Union. Due to the
      fact that milk is used by all the age groups including infants and children in
      Fariman city, it is necessary to minimize the health risk from AFM1 contamination
      in milk. For this reason, the level of its precursor, aflatoxin B1 (AFB1), in
      dairy feeds must be reduced, requiring constant aflatoxin monitoring of relevant
      agricultural commodities. 

PMID- 24026512
TI  - Determination of the density of human nuclear cataract lenses.
AB  - The aim of the present study was to detect senile nuclear cataract lens density
      and provide a quantitative measurement of lens density for the long-term clinical
      observation of cataracts. An Anterior Segment Analysis System was used to detect
      the lens density of 422 simple senile cataract eyes and normal contralateral
      eyes. The density values were taken at the optical axis at various depths
      measured from the anterior capsule. The differences in lens density at various
      photographic orientations and in various nuclear grading groups were
      investigated. The density at 90 orientation was larger than that at 30 and 150
      (P<0.05). The density was reduced beyond the 1.0-mm depth point in all the
      lenses. Prior to the 2.5-mm depth point, there were differences among the five
      grade groups (P<0.05). Beyond the 3.0-mm depth point, values in all the grade
      groups were low and not significantly different (P>0.05). In the grade 4 group,
      the decrease was more evident. The average density values at all the depth points
      showed a tendency to increase with increasing nuclear grade. Measuring the
      density of the anterior half of the lens at 90 orientation is therefore more
      reliable compared with that of the posterior half and at other orientations.
      Results of the present study have shown that the Anterior Segment Analysis System
      may be used to detect senile nuclear cataract lens density and provide a
      quantitative measurement of lens density for long-term clinical observation of
      cataracts.

PMID- 24026513
TI  - Identifying and characterizing Yarrowia keelungensis sp. nov., an oil-degrading
      yeast isolated from the sea surface microlayer.
AB  - Ascomycetous yeast strain SM-22 was isolated from the sea-surface microlayer near
      the Keelung City off the northern coast of Taiwan. This strain showed a cell
      surface hydrophobicity higher than 90 %, moderate UV A/B resistance, and it
      degraded 68 % of the total petroleum hydrocarbon content of an artificial
      seawater medium containing 1 % (v v(-1)) diesel oil within 15 days at 25  degrees
      C. The closest phylogenetic relative of this strain is Candida oslonensis CBS
      10146(T), but it differs from strain SM-22 by a 3.7 % divergence (including 18
      nucleotide substitutions and 2 gaps) in the D1/D2 domain sequence of the large
      subunit rRNA gene. This difference clearly suggests that the strain SM-22
      represents a distinct species. Strain SM-22 does not produce ascospores on common
      sporulation media and it can therefore be considered an anamorph of the genus
      Yarrowia. Thus, the name Yarrowia keelungensis sp. nov. (type strain SM-22(T) =
      BCRC 23110(T) = JCM 14894(T) = CBS 11062(T)) is proposed as a novel species of
      genus Yarrowia.

PMID- 24026514
TI  - Introduction of a new critical p value correction method for statistical
      significance analysis of metabonomics data.
AB  - Nuclear magnetic resonance (NMR) spectroscopy-based metabonomics is of growing
      importance for discovery of human disease biomarkers. Identification and
      validation of disease biomarkers using statistical significance analysis (SSA) is
      critical for translation to clinical practice. SSA is performed by assessing a
      null hypothesis test using a derivative of the Student's t test, e.g., a Welch's
      t test. Choosing how to correct the significance level for rejecting null
      hypotheses in the case of multiple testing to maintain a constant family-wise
      type I error rate is a common problem in such tests. The multiple testing problem
      arises because the likelihood of falsely rejecting the null hypothesis, i.e., a
      false positive, grows as the number of tests applied to the same data set
      increases. Several methods have been introduced to address this problem.
      Bonferroni correction (BC) assumes all variables are independent and therefore
      sacrifices sensitivity for detecting true positives in partially dependent data
      sets. False discovery rate (FDR) methods are more sensitive than BC but uniformly
      ascribe highest stringency to lowest p value variables. Here, we introduce
      standard deviation step down (SDSD), which is more sensitive and appropriate than
      BC for partially dependent data sets. Sensitivity and type I error rate of SDSD
      can be adjusted based on the degree of variable dependency. SDSD generates
      fundamentally different profiles of critical p values compared with FDR methods
      potentially leading to reduced type II error rates. SDSD is increasingly
      sensitive for more concentrated metabolites. SDSD is demonstrated using NMR-based
      metabonomics data collected on three different breast cancer cell line extracts. 

PMID- 24026515
TI  - Electrochemical transduction of DNA hybridization at modified electrodes by using
      an electroactive pyridoacridone intercalator.
AB  - A synthetic redox probe structurally related to natural pyridoacridones was
      designed and electrochemically characterised. These heterocycles behave as DNA
      intercalators due to their extended planar structure that promotes stacking in
      between nucleic acid base pairs. Electrochemical characterization by cyclic
      voltammetry revealed a quasi-reversible electrochemical behaviour occurring at a
      mild negative potential in aqueous solution. The study of the mechanism showed
      that the iminoquinone redox moiety acts similarly to quinone involving a two
      electron reduction coupled with proton transfer. The easily accessible potential
      region with respect to aqueous electro-inactive window makes the pyridoacridone
      ring suitable for the indirect electrochemical detection of chemically unlabelled
      DNA. Its usefulness as electrochemical hybridization indicator was assessed on
      immobilised DNA and compared to doxorubicin. The voltamperometric response of the
      intercalator acts as an indicator of the presence of double-stranded DNA at the
      electrode surface and allows the selective transduction of immobilised
      oligonucleotide hybridization at both macro- and microscale electrodes. 

PMID- 24026516
TI  - An analytical workflow for the molecular dissection of irreversibly modified
      fluorescent proteins.
AB  - Owing to their ability to be genetically expressed in live cells, fluorescent
      proteins have become indispensable markers in cellular and biochemical studies.
      These proteins can undergo a number of covalent chemical modifications that may
      affect their photophysical properties. Among other mechanisms, such covalent
      modifications may be induced by reactive oxygen species (ROS), as generated along
      a variety of biological pathways or through the action of ionizing radiations. In
      a previous report [1], we showed that the exposure of cyan fluorescent protein
      (ECFP) to amounts of (*)OH that mimic the conditions of intracellular oxidative
      bursts (associated with intense ROS production) leads to observable changes in
      its photophysical properties in the absence of any direct oxidation of the ECFP
      chromophore. In the present work, we analyzed the associated structural
      modifications of the protein in depth. Following the quantified production of
      (*)OH, we devised a complete analytical workflow based on chromatography and mass
      spectrometry that allowed us to fully characterize the oxidation events. While
      methionine, tyrosine, and phenylalanine were the only amino acids that were found
      to be oxidized, semi-quantitative assessment of their oxidation levels showed
      that the protein is preferentially oxidized at eight residue positions. To
      account for the preferred oxidation of a few, poorly accessible methionine
      residues, we propose a multi-step reaction pathway supported by data from pulsed
      radiolysis experiments. The described experimental workflow is widely
      generalizable to other fluorescent proteins, and opens the door to the
      identification of crucial covalent modifications that affect their photophysics. 

PMID- 24026518
TI  - Government sets out five year plan for tackling "ticking time bomb" of antibiotic
      resistance.

PMID- 24026517
TI  - Mass spectrometric monitoring of Sr-enriched bone cements--from in vitro to in
      vivo.
AB  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a well-established
      technique in materials science, but is now increasingly applied also in the life
      sciences. Here, we demonstrate the potential of this analytical technique for use
      in the development of new bone implant materials. We tracked strontium-enriched
      calcium phosphate cements, which were developed for the treatment of osteoporotic
      bone, from in vitro to in vivo. Essentially, the spatial distribution of
      strontium in two different types of strontium-modified calcium phosphate cements
      is analysed by SIMS depth profiling. To gain information about the strontium
      release kinetics, the cements were immersed for 3, 7, 14 and 21 days in alpha-MEM
      and tris(hydroxymethyl)-aminomethane solution and analysed afterwards by ToF-SIMS
      depth profiling. For cements stored in alpha-MEM solution an inhibited strontium
      release was observed. By using principal component analysis to evaluate TOF-SIMS
      surface spectra, we are able to prove the adsorption of proteins on the cement
      surface, which inhibit the release kinetics. Cell experiments with human
      osteoblast-like cells cultured on the strontium-modified cements and subsequent
      mass spectrometric analysis of the mineralised extracellular matrix (mECM) prove
      clearly that strontium is incorporated into the mECM of the osteoblast-like
      cells. Finally, in an animal experiment, the strontium-doped cements are
      implanted into the femur of osteoporotic rats. After 6 weeks, only a slight
      release of strontium was found in the vicinity of the implant material. By using
      ToF-SIMS, it is proven that strontium is localised in regions of newly formed
      bone but also within the pre-existing tissue. 

PMID- 24026519
TI  - Validation of the Yale Swallow Protocol: a prospective double-blinded
      videofluoroscopic study.
AB  - The purpose of this prospective, double-blinded, multirater, systematic
      replication study was to investigate agreement for aspiration risk, in the same
      individual, between videofluoroscopic swallow studies (VFSS) and the Yale Swallow
      Protocol. Participants were 25 consecutive adults referred for dysphagia testing
      who met the inclusion criteria of completion of a brief cognitive assessment,
      oral mechanism examination, and no tracheotomy tube. First, all participants were
      administered the Yale Swallow Protocol by two experienced speech-language
      pathologists trained in protocol administration. Failure criteria were inability
      to drink the entire amount, interrupted drinking, or coughing during or
      immediately after drinking. Second, all participants completed a VFSS within 5-10
      min of protocol administration. A speech-language pathologist, blinded to
      protocol results, reviewed the VFSS to determine aspiration status in a binary
      (yes/no) manner. Inter-rater agreement between two speech-language pathologists
      was 100 % for identification of aspiration risk with the Yale Swallow Protocol.
      Inter-rater agreement between the speech-language pathologist and the radiologist
      for identification of aspiration status with VFSS was 100 %. Twenty percent of
      VFSS recordings were viewed again 3-6 months after initial data collection, and
      intrarater agreement for identification of thin liquid aspiration was 100 %.
      Sensitivity for the Yale Swallow Protocol = 100 %, specificity = 64 %, positive
      predictive value = 78 %, and negative predictive value = 100 %. Importantly, all
      participants who passed the protocol did not aspirate during VFSS. Multiple,
      double-blinded raters and VFSS as the reference standard agreed with previous
      research with a single, nonblinded rater and FEES as the reference standard for
      identification of aspiration risk. The clinical usefulness and validity of the
      Yale Swallow Protocol for determining aspiration risk in a small sample size of
      male participants has been confirmed. Future research is needed with a larger and
      more heterogeneous population sample. 

PMID- 24026520
TI  - Bedside screening to detect oropharyngeal dysphagia in patients with neurological
      disorders: an updated systematic review.
AB  - Oropharyngeal dysphagia is a highly prevalent comorbidity in neurological
      patients and presents a serious health threat, which may le to outcomes of
      aspiration pneumonia ranging from hospitalization to death. Therefore, an early
      identification of risk followed by an accurate diagnosis of oropharyngeal
      dysphagia is fundamental. This systematic review provides an update of currently
      available bedside screenings to identify oropharyngeal dysphagia in neurological
      patients. An electronic search was carried out in the databases PubMed, Embase,
      CINAHL, and PsychInfo (formerly PsychLit), and all hits from 2008 up to December
      2012 were included in the review. Only studies with sufficient methodological
      quality were considered, after which the psychometric characteristics of the
      screening tools were determined. Two relevant bedside screenings were identified,
      with a minimum sensitivity and specificity of >=70 and >=60 %, respectively. 

PMID- 24026521
TI  - Safety evaluation of nasopharyngeal cooling (RhinoChill(r)) in stroke patients:
      an observational study.
AB  - INTRODUCTION: New technologies for therapeutic cooling have become available. The
      objective of our study was to investigate the safety of nasopharyngeal cooling
      with the RhinoChill((r)) device in stroke patients, focusing on systemic and
      neurovital parameters. METHODS: In this prospective observational study,
      consecutive patients with severe ischemic or hemorrhagic stroke who underwent
      intracranial pressure (ICP) and brain temperature monitoring have been enrolled.
      Ten patients who were treated with the RhinoChill((r)) device were analyzed.
      Brain and bladder temperature and systemic and neurovital parameters were
      monitored continuously. Additional evaluations of safety included bleeding
      complications and otolaryngological examinations. RESULTS: Baseline brain
      temperature of 36.7  degrees C (SD 0.9) decreased by an average of 1.21  degrees
      C (SD 0.46) within 1 h, the effect of brain temperature decrease ranged from a
      maximum of 2  degrees C (patients 3 and 7) to a minimum of 0.6  degrees C
      (patient 4). Within the first several minutes after initiating RhinoChill((r))
      treatment, 3 of 10 patients experienced an increase in systolic arterial pressure
      by 30, 30, and 53 mmHg, respectively. Heart rate rose as well (mean 3 bpm, SD
      2.9). ICP and oxygen saturation were unaffected by the treatment. We observed 1
      bleeding complication in the control CT scan of patient 10. Rhinoscopical
      findings 3 days after nasopharyngeal cooling and at the follow-up (>6 months) and
      a 16-item smell test were normal. CONCLUSION: The RhinoChill((r)) system cools
      the brain efficiently. However, steep increases in blood pressure raise serious
      concerns regarding the safety of its use in stroke patients.

PMID- 24026522
TI  - Safety and efficacy of repeated doses of 14.6 or 23.4 % hypertonic saline for
      refractory intracranial hypertension.
AB  - BACKGROUND: The efficacy of administering single bolus doses of 14.6 or 23.4 %
      hypertonic saline (HTS) to treat refractory intracranial hypertension has been
      demonstrated in the literature and has emerged as an important therapeutic option
      in treating these patients. However, many institutions lack experience with this
      therapy and there are few published studies evaluating the safety of repeated
      bolus dosing of HTS. METHODS: A retrospective review of patients admitted between
      January 2008 and July 2012 was conducted to evaluate the use of repeated dosing
      of HTS in patients with refractory intracranial hypertension. The primary
      objective was to evaluate the safety of repeated dosing of HTS assessed by
      documented adverse effects such as central pontine myelinolysis (CPM) and severe
      fluctuations in serum sodium concentrations. Secondary objectives were to
      evaluate the efficacy of repeated dosing HTS in reducing intracranial pressure
      (ICP) and to compare the dose-response relationship of 14.6 and 23.4 % doses.
      RESULTS: Fifty-five patients were included for evaluation, each receiving an
      average of 8.9 (range 2-61) doses of HTS. A statistically significant increase in
      mean serum sodium concentration occurred with the administration of HTS (p <
      0.0001). No cases of CPM were identified. The use of HTS was found to be
      effective based on decreases in ICP after administration (p < 0.0001, mean ICP
      reduction: 10.1 mmHg, range 3-23.6 mmHg). The efficacy of 23.4 % saline in
      decreasing ICP was not found to be significantly different than 14.6 % saline (p
      = 0.23). CONCLUSIONS: Repeat bolus dosing of 14.6 or 23.4 % HTS appears to be
      relatively safe and effective for treating refractory intracranial hypertension
      assuming there is frequent electrolyte monitoring and concomitant fluid
      management.

PMID- 24026524
TI  - A Food Handler-Associated, Foodborne Norovirus GII.4 Sydney 2012-Outbreak
      Following a Wedding Dinner, Austria, October 2012.
AB  - On October 12, 2012, the provincial public health directorate of Salzburg
      reported a suspected norovirus (NV) outbreak among guests of a wedding-reception.
      The investigation aimed to confirm the causative agent, to identify the mode of
      transmission and to implement appropriate preventive measures. A probable
      outbreak case was defined as a wedding guest with diarrhoea or vomiting with
      disease onset from 7 to 10 October 2012 and who consumed food at the wedding
      dinner prepared by a hotel in the province Salzburg on 6 October 2012. A
      confirmed outbreak case fulfilled the criteria of a probable outbreak case and
      had a laboratory-confirmed NV infection. We conducted a cohort-investigation
      among the wedding guests. The case definitions were fulfilled in 26 wedding
      guests (25 %) including 2 confirmed cases. Females were 3.2 times more likely to
      develop disease (95 % CI 1.4-7.2) as compared to males. A mushroom dish was found
      to be associated with disease risk among females (risk ratio 2.3, 95 % CI 1.2
      4.3). Two of 2 tested case-patients and 6 of 14 kitchen workers tested were
      positive for NV GII.4 Sydney. One kitchen staff-member worked during the wedding
      dinner despite diarrhoea. No food safety training was documented for the
      employees and the kitchen staff's restroom was lacking operational facilities for
      hand hygiene. We report the first investigated outbreak due to GII.4 Sydney,
      which was likely due to a symptomatic kitchen worker. Gender-specific eating
      behaviour may have posed female guests at higher risk of NV infection.

PMID- 24026523
TI  - Cognitive-behavioral therapy vs risperidone for augmenting serotonin reuptake
      inhibitors in obsessive-compulsive disorder: a randomized clinical trial.
AB  - IMPORTANCE: Obsessive-compulsive disorder (OCD) is one of the world's most
      disabling illnesses according to the World Health Organization. Serotonin
      reuptake inhibitors (SRIs) are the only medications approved by the Food and Drug
      Administration to treat OCD, but few patients achieve minimal symptoms from an
      SRI alone. In such cases, practice guidelines recommend adding antipsychotics or
      cognitive-behavioral therapy consisting of exposure and ritual prevention
      (EX/RP). OBJECTIVE: To compare the effects of these 2 SRI augmentation strategies
      vs pill placebo for the first time, to our knowledge, in adults with OCD. DESIGN,
      SETTING, AND PARTICIPANTS: A randomized clinical trial (conducted January 2007
      August 2012) at 2 academic outpatient research clinics that specialize in OCD and
      anxiety disorders. Patients (aged 18-70 years) were eligible if they had OCD of
      at least moderate severity despite a therapeutic SRI dose for at least 12 weeks
      prior to entry. Of 163 who were eligible, 100 were randomized (risperidone, n =
      40; EX/RP, n = 40; and placebo, n = 20), and 86 completed the trial.
      INTERVENTIONS: While continuing their SRI at the same dose, patients were
      randomized to the addition of 8 weeks of risperidone (up to 4 mg/d), EX/RP (17
      sessions delivered twice weekly), or pill placebo. Independent assessments were
      conducted every 4 weeks. MAIN OUTCOME AND MEASURE: The Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) to measure OCD severity. RESULTS: Patients randomized
      to EX/RP had significantly greater reduction in week 8 Y-BOCS scores based on
      mixed-effects models (vs risperidone: mean [SE], -9.72 [1.38]; P < .001 vs
      placebo: mean [SE], -10.10 [1.68]; P < .001). Patients receiving risperidone did
      not significantly differ from those receiving placebo (mean [SE], -0.38 [1.72]; P
      = .83). More patients receiving EX/RP responded (Y-BOCS score decrease >=25%: 80%
      for EX/RP, 23% for risperidone, and 15% for placebo; P < .001). More patients
      receiving EX/RP achieved minimal symptoms (Y-BOCS score <=12: 43% for EX/RP, 13%
      for risperidone, and 5% for placebo; P = .001). Adding EX/RP was also superior to
      risperidone and placebo in improving insight, functioning, and quality of life.
      CONCLUSIONS AND RELEVANCE: Adding EX/RP to SRIs was superior to both risperidone
      and pill placebo. Patients with OCD receiving SRIs who continue to have
      clinically significant symptoms should be offered EX/RP before antipsychotics
      given its superior efficacy and less negative adverse effect profile. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00389493.

PMID- 24026525
TI  - Dioxin pollution disrupts reproduction in male Japanese field mice.
AB  - Dioxins cause various adverse effects in animals including teratogenesis,
      induction of drug metabolizing enzymes, tumor promotion, and endocrine
      disruption. Above all, endocrine disruption is known to disturb reproduction in
      adult animals and may, also seriously impact their offspring. However, most
      previous studies have quantified the species-specific accumulation of dioxins,
      whereas few studies have addressed the physiological impacts of dioxins on
      wildlife, such as reduced reproductive function. Here we clarify an effect of
      endocrine disruption caused by dioxins on the Japanese field mouse, Apodemus
      speciosus. Japanese field mice collected from various sites polluted with dioxins
      accumulated high concentrations of dioxins in their livers. Some dioxin
      congeners, especially, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 3,3',4,4',5
      pentachloro biphenyl, 1,2,3,4,6,7,8-heptachlorodibenzofuran, and
      octachlorodibenzo-p-dioxin, which showed high biota-soil accumulation factors,
      contributed to concentration of dioxins in mouse livers with an increase of
      accumulation of total dioxins. As for physiological effects on the Japanese field
      mouse, high levels of cytochrome P450 1A1 (CYP1A1) mRNA, a drug metabolizing
      enzyme induced by dioxins, were found in the livers of mice captured at polluted
      sites. Furthermore, at such sites polluted with dioxins, increased CYP1A1
      expression coincided with reduced numbers of active spermatozoa in mice. Thus,
      disruption in gametogenesis observed in these mice suggests that dioxins not only
      negatively impact reproduction among Japanese field mice, but might also act as a
      kind of selection pressure in a chemically polluted environment. 

PMID- 24026526
TI  - Lethal and sub lethal effects of the biocide chlorhexidine on aquatic organisms.
AB  - Chlorhexidine is among the most used biocides in Europe, however its toxicity to
      aquatic organisms is scarcely known. The main objective of this study was to
      assess the lethal and sub lethal effects of chlorhexidine digluconate (ChD) on
      four aquatic model organisms: the bacteria Vibrio fischeri, the algae
      Pseudokirchneriella subcapitata, the crustacean Daphnia magna and the embryos of
      the fish Danio rerio. ChD was very toxic to algae and crustaceans, with a 72 h
      EC50 of 62.2 MUg/l and a 48 h-EC50 of 45.0 MUg/l, respectively. Toxicity to fish
      embryos and the bacteria was lower, with a 96 h-EC50 of 804.0 MUg/l and a 15 min
      EC50 of 1,694.0 MUg/l, respectively. Concerning sub lethal effects on D. magna
      (feeding inhibition) a 6 h-EC50 of 503.7 MUg/l was obtained. In fish, ChD caused
      developmental abnormalities, namely alterations in the amniotic fluid (48 h-EC20
      of 753.6 MUg/l) and early hatching. Moreover, enzymatic biomarkers on fish
      embryos showed an induction of cholinesterase activity in all ChD tested
      concentrations (80-900 MUg/l). The catalase activity was also induced at the
      highest concentration tested (900 MUg/l) whereas no changes were observed for
      glutathione-S-transferase and lactate dehydrogenase activities. The toxicity of
      ChD to the algae and crustacean raises concerns about its potential effects in
      aquatic food webs, since these organisms are in the base of trophic chains, and
      highlights the need for further studies on ChD toxicity to aquatic organisms.

PMID- 24026527
TI  - Cross-cultural adaptation and validation of the Turkish version of the Hip
      disability and Osteoarthritis Outcome Score-Physical function Short-form (HOOS
      PS).
AB  - The purpose of this study is to adapt the Hip disability and Osteoarthritis
      Outcome Score-Physical function Short-form (HOOS-PS) to Turkish language and to
      evaluate the psychometric properties of the Turkish version in patients with
      primary hip osteoarthritis. After the translation from the source language
      (English) to the target language (Turkish), synthesis, back translation,
      revision, and pretest stages were done. Next, 50 patients with primary hip
      osteoarthritis were asked to fill out the Turkish version of the HOOS-PS two
      times with one week interval. Internal consistency was tested using the
      Cronbach's alpha coefficient, and test-retest reliability was assessed by
      calculating the intra-class correlation coefficient (ICC). Construct validity was
      investigated by comparing the results of the HOOS-PS and WOMAC, Lequesne
      questionnaries using Spearman's rank correlation coefficient. Internal
      consistency was good with a Cronbach's alpha of 0.778 (>0.7) and ICC was 0.911
      (>0.7). Both scores verify that the Turkish HOOS-PS is a reliable tool.
      Spearman's rank correlation coefficients between the HOOS-PS and overall WOMAC (r
      = 0.653), WOMAC physical functions (r = 0.626), WOMAC pain (r = 0.629) subscales,
      overall Lequesne (r = 0.650), and Lequesne daily living activities (r = 0.620)
      subscales were high (r > 0.6), and moderate correlations were found between the
      HOOS-PS and WOMAC stiffness (r = 0.511), Lequesne pain (r = 0.569), and Lequesne
      walking distance (r = 0.578) subscales (0.6 > r > 0.2), thus providing proof for
      the validity of the Turkish form. The Turkish HOOS-PS was found to be reliable
      and valid for patients with primary hip osteoarthritis.

PMID- 24026528
TI  - As compared to allopurinol, urate-lowering therapy with febuxostat has superior
      effects on oxidative stress and pulse wave velocity in patients with severe
      chronic tophaceous gout.
AB  - We prospectively evaluated whether an effective 12-month uric acid-lowering
      therapy (ULT) with the available xanthine oxidase (XO) inhibitors allopurinol and
      febuxostat in patients with chronic tophaceous gout has an impact on oxidative
      stress and/or vascular function. Patients with chronic tophaceous gout who did
      not receive active ULT were included. After clinical evaluation, serum uric acid
      levels (SUA) and markers of oxidative stress were measured, and carotid-femoral
      pulse wave velocity (cfPWV) was assessed. Patients were then treated with
      allopurinol (n = 9) or with febuxostat (n = 8) to target a SUA level <= 360
      MUmol/L. After 1 year treatment, the SUA levels, markers of oxidative stress and
      the cfPWV were measured again. Baseline characteristics of both groups showed no
      significant differences except a higher prevalence of moderate impairment of
      renal function (estimated glomerular filtration rate <60 ml/min) in the
      febuxostat group. Uric acid lowering with either inhibitors of XO resulted in
      almost equally effective reduction in SUA levels. The both treatment groups did
      not differ in their baseline cfPWV (allopurinol group: 14.1 +/- 3.4 m/s,
      febuxostat group: 13.7 +/- 2.7 m/s, p = 0.80). However, after 1 year of therapy,
      we observed a significant cfPWV increase in the allopurinol group (16.8 +/- 4.3
      m/s, p = 0.001 as compared to baseline), but not in the febuxostat patients (13.3
      +/- 2.3 m/s, p = 0.55). Both febuxostat and allopurinol effectively lower SUA
      levels in patients with severe gout. However, we observed that febuxostat also
      appeared to be beneficial in preventing further arterial stiffening. Since
      cardiovascular events are an important issue in treating patients with gout, this
      unexpected finding may have important implications and should be further
      investigated in randomized controlled trials.

PMID- 24026530
TI  - Neuropilin-2 contributes to tumorigenicity in a mouse model of Hedgehog pathway
      medulloblastoma.
AB  - The Hedgehog (Hh) signaling pathway has been implicated in the most common
      childhood brain tumor, medulloblastoma (MB). Given the toxicity of post-surgical
      treatments for MB, continued need exists for new, targeted therapies. Based upon
      our finding that Neuropilin (Nrp) transmembrane proteins are required for Hh
      signal transduction, we investigated the role of Nrp in MB cells. Cultured cells
      derived from a mouse Ptch (+/-) ;LacZ MB (Med1-MB), effectively modeled the Hh
      pathway-related subcategory of human MBs in vitro. Med1-MB cells maintained
      constitutively active Hh target gene transcription, and consistently formed
      tumors within one month after injection into mouse cerebella. The proliferation
      rate of Med1-MBs in culture was dependent upon Nrp2, while reducing Nrp1 function
      had little effect. Knockdown of Nrp2 prior to cell implantation significantly
      increased mouse survival, compared to transfection with a non-targeting siRNA.
      Knocking down Nrp2 specifically in MB cells avoided any direct effect on tumor
      vascularization. Nrp2 should be further investigated as a potential target for
      adjuvant therapy in patients with MB.

PMID- 24026531
TI  - Optimization of the route of platinum drugs administration to optimize the
      concomitant treatment with radiotherapy for glioblastoma implanted in the Fischer
      rat brain.
AB  - Treatment of glioblastoma with platinum compounds modestly improves progression
      free survival and may cause toxic effects which prevent use at higher dose that
      would otherwise improve the antineoplastic effect. To reduce toxicity, we propose
      to encapsulate the platinum drug in a liposome. We have also tested three methods
      of drug administration (intra-venous, intra-arterial and intra-arterial combined
      with blood brain barrier disruption) to determine which one optimizes the tumor
      cell uptake, limits the toxicity and delivers the best concomitance effect with
      radiotherapy. Cisplatin, oxaliplatin, their respective liposomal formulations,
      LipoplatinTM and LipoxalTM, and carboplatin were assessed in F98 glioma,
      orthotopically implanted in Fischer rats. We found that the modest accumulation
      of drugs in tumor cells after intra-venous injection was significantly improved
      when the intra-arterial route was used and further increased after the transient
      opening of the blood brain barrier with mannitol. The liposomal formulations have
      largely reduced the toxicity and have allowed a better exploitation of the anti
      cancer activity of platinum agent. Although the liposomes LipoplatinTM and
      LipoxalTM have shown a similar ability to that of carboplatin, to accumulate in
      brain tumors, the highest additive effect with radiotherapy was obtained with
      carboplatin. We conclude that the intra-arterial infusion of carboplatin or
      LipoxalTM in concomitance with radiation therapy leads to the best tumor control
      as measured by an increase of mean survival time in Fischer rats implanted with
      the F98 glioma with a benefit in survival time of 13.4 and 6.5 days respectively
      compared to intra-venous.

PMID- 24026532
TI  - Solid state pathways to complex shape evolution and tunable porosity during
      metallic crystal growth.
AB  - Growing complex metallic crystals, supported high index facet nanocrystal
      composites and tunable porosity metals, and exploiting factors that influence
      shape and morphology is crucial in many exciting developments in chemistry,
      catalysis, biotechnology and nanoscience. Assembly, organization and ordered
      crystallization of nanostructures into complex shapes requires understanding of
      the building blocks and their association, and this relationship can define the
      many physical properties of crystals and their assemblies. Understanding crystal
      evolution pathways is required for controlled deposition onto surfaces. Here,
      complex metallic crystals on the nano- and microscale, carbon supported
      nanoparticles, and spinodal porous noble metals with defined inter-feature
      distances in 3D, are accomplished in the solid-state for Au, Ag, Pd, and Re.
      Bottom-up growth and positioning is possible through competitive coarsening of
      mobile nanoparticles and their site-specific crystallization in a nucleation
      dewetted matrix. Shape evolution, density and growth mechanism of complex
      metallic crystals and porous metals can be imaged during growth. 

PMID- 24026533
TI  - Does nonmarital childbearing and mother's later marriage influence child health
      in adolescence? Policy brief.

PMID- 24026534
TI  - "Feeling disorder" as a comparative and contingent process: gender, neighborhood
      conditions, and adolescent mental health.
AB  - We explore the effects of neighborhood social disorder on internalizing symptoms
      among urban youth by focusing on three questions. First, we ask whether the
      impact of social disorder on internalizing symptoms results from comparisons with
      conditions measured locally or across the entire city.  Second, we consider
      whether neighborhood collective efficacy modifies disorder's effect on
      internalizing symptoms. Finally,  we assess whether these effects vary by gender.
      Analyses of survey data on 2,367 youth from the Project on Human Development in
      Chicago Neighborhoods indicate that social disorder is positively associated with
      girls' internalizing symptoms when measured as a deviation from a neighborhood
      cluster (NC--two to three census tracts) mean. High collective efficacy within
      girls' NCs attenuates disorder effects on their internalizing symptoms. We find
      no evidence of disorder or collective efficacy effects on boys' internalizing
      symptoms.

PMID- 24026535
TI  - Racial-ethnic disparities in maternal parenting stress: the role of structural
      disadvantages and parenting values.
AB  - Although researchers contend that racial-ethnic minorities experience more stress
      than whites, knowledge of racial-ethnic disparities in parenting stress is
      limited. Using a pooled time-series analysis of data from the Early Childhood
      Longitudinal Study, Kindergarten Class of 1998-99 (n = 11,324), we examine racial
      ethnic differences in maternal parenting stress, with a focus on structural and
      cultural explanations and variations by nativity and child age. In kindergarten,
      black mothers, albeit U.S.-born only, report more parenting stress than white
      mothers due to structural disadvantages and authoritarian parenting values. The
      black-white gap increases from kindergarten to third grade, and in third grade,
      U.S.-born black mothers' higher stress than white mothers' persists after
      controlling for structural and parenting factors. Hispanic and Asian mothers,
      albeit foreign-born only, report more stress than white mothers at both ages due
      to structural disadvantages and authoritarian values. Despite structural
      disadvantages, American Indian mothers report less stress. 

PMID- 24026536
TI  - Yeast Mnn9 is both a priming glycosyltransferase and an allosteric activator of
      mannan biosynthesis.
AB  - The fungal cell possesses an essential carbohydrate cell wall. The outer layer,
      mannan, is formed by mannoproteins carrying highly mannosylated O- and N-linked
      glycans. Yeast mannan biosynthesis is initiated by a Golgi-located complex (M-Pol
      I) of two GT-62 mannosyltransferases, Mnn9p and Van1p, that are conserved in
      fungal pathogens. Saccharomyces cerevisiae and Candida albicans mnn9 knockouts
      show an aberrant cell wall and increased antibiotic sensitivity, suggesting the
      enzyme is a potential drug target. Here, we present the structure of ScMnn9 in
      complex with GDP and Mn(2+), defining the fold and catalytic machinery of the GT
      62 family. Compared with distantly related GT-78/GT-15 enzymes, ScMnn9 carries an
      unusual extension. Using a novel enzyme assay and site-directed mutagenesis, we
      identify conserved amino acids essential for ScMnn9 'priming' alpha-1,6
      mannosyltransferase activity. Strikingly, both the presence of the ScMnn9 protein
      and its product, but not ScMnn9 catalytic activity, are required to activate
      subsequent ScVan1 processive alpha-1,6-mannosyltransferase activity in the M-Pol
      I complex. These results reveal the molecular basis of mannan synthesis and will
      aid development of inhibitors targeting this process. 

PMID- 24026538
TI  - Diabetes in relation to breast cancer relapse and all-cause mortality in elderly
      breast cancer patients: a FOCUS study analysis.
AB  - BACKGROUND: In developed countries, 40% of breast cancer patients are >65 years
      of age at diagnosis, of whom 16% additionally suffer from diabetes. The aim of
      this study was to assess the impact of diabetes on relapse-free period (RFP) and
      overall mortality in elderly breast cancer patients. PATIENTS AND METHODS:
      Patients were selected from the retrospective FOCUS cohort, which contains
      detailed information of elderly breast cancer patients. RFP was calculated using
      Fine and Gray competing risk regression models for patients with diabetes versus
      patients without diabetes. Overall survival was calculated by Cox regression
      models, in which patients were divided into four groups: no comorbidity, diabetes
      only, diabetes and other comorbidity or other comorbidity without diabetes.
      RESULTS: Overall, 3124 patients with non-metastasized breast cancer were
      included. RFP was better for patients with diabetes compared with patients
      without diabetes (multivariable HR 0.77, 95% CI 0.59-1.01), irrespective of other
      comorbidity and most evident in patients aged >=75 years (HR 0.67, 95% CI 0.45
      0.98). The overall survival was similar for patients with diabetes only compared
      with patients without comorbidity (HR 0.86, 95% CI 0.45-0.98), while patients
      with diabetes and additional comorbidity had the worst overall survival (HR 1.70,
      95% CI 1.44-2.01). CONCLUSION: When taking competing mortality into account, RFP
      was better in elderly breast cancer patients with diabetes compared with patients
      without diabetes. Moreover, patients with diabetes without other comorbidity had
      a similar overall survival as patients without any comorbidity. Possibly,
      unfavourable effects of (complications of) diabetes on overall survival are
      counterbalanced by beneficial effects of metformin on the occurrence of breast
      cancer recurrences.

PMID- 24026537
TI  - MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic
      recombination.
AB  - The histone-fold proteins Mhf1/CENP-S and Mhf2/CENP-X perform two important
      functions in vertebrate cells. First, they are components of the constitutive
      centromere-associated network, aiding kinetochore assembly and function. Second,
      they work with the FANCM DNA translocase to promote DNA repair. However, it has
      been unclear whether there is crosstalk between these roles. We show that Mhf1
      and Mhf2 in fission yeast, as in vertebrates, serve a dual function, aiding DNA
      repair/recombination and localizing to centromeres to promote chromosome
      segregation. Importantly, these functions are distinct, with the former being
      dependent on their interaction with the FANCM orthologue Fml1 and the latter not.
      Together with Fml1, they play a second role in aiding chromosome segregation by
      processing sister chromatid junctions. However, a failure of this activity does
      not manifest dramatically increased levels of chromosome missegregation due to
      the Mus81-Eme1 endonuclease, which acts as a failsafe to resolve DNA junctions
      before the end of mitosis. 

PMID- 24026539
TI  - Assessment of SHOX2 methylation in EBUS-TBNA specimen improves accuracy in lung
      cancer staging.
AB  - BACKGROUND: Endobronchial ultrasound with transbronchial needle aspiration (EBUS
      TBNA) is a well-established method to assess mediastinal lymph nodes for lung
      cancer. However, a proportion of patients require further investigation, due to
      the low negative predictive value (NPV). The objective of this study was to
      determine whether the assessment of short stature homeobox 2 (SHOX2) DNA
      methylation level in lymph node tissue obtained by EBUS-TBNA improves the
      accuracy of mediastinal staging. PATIENTS AND METHODS: EBUS-TBNA was carried out
      for suspicious lymph nodes of 154 patients. Negative or ambiguous histological
      results were confirmed by surgical means and clinical follow-up over 6 months.
      EBUS-TBNA was assessed on 80 positive and 85 negative classified lymph nodes and
      compared with the result of the SHOX2 DNA methylation real-time PCR analysis.
      Relative methylation measured by delta-delta cycle threshold (DeltaDeltaCt) was
      used to classify the samples. Clinical performance of the EBUS-TBNA procedure
      with and without the additional SHOX2 assessment was calculated against the final
      classification according to the gold standard. RESULTS: Based on data from 105
      patients, an average 80-fold increase in the SHOX2 methylation level was measured
      for positive compared with negative lymph nodes. SHOX2 results with a
      DeltaDeltaCt value of <6.5 indicate positive lymph nodes. Applying this molecular
      analysis to EBUS-TBNA cases, not diagnosed by pathologic assessment, the
      sensitivity of staging was improved by 17%-99%. The NPV increased from 80% to
      99%. CONCLUSIONS: The combination of EBUS-TBNA and SHOX2 methylation level
      strongly improves the assessment of the nodal status by identifying additional
      malignant lesions and confirming benign nodes and therefore avoiding invasive
      follow-up procedures.

PMID- 24026541
TI  - Robustaside B and para-hydroxyphenol: phenolic and antioxidant compounds purified
      from Cnestis ferruginea D.C induced membrane permeability transition in rat liver
      mitochondria.
AB  - The antioxidant properties of robustaside B and para-hydroxyphenol isolated from
      Cnestis ferruginea were measured as the rate of inhibition of thiobarbituric acid
      reactive substance (TBARS) production in the Fe2+/ascorbate system. The
      modulatory effects of the compounds on mitochondrial membrane permeability
      transition (MMPT) were monitored spectrophotometrically as decreases in light
      scattering at 540 nm. The varying concentrations of robustaside B and para
      hydroxyphenol (0.05, 0.1, 0.2, 0.25, 0.5, 0.75 and 1 mM) significantly reduced
      (P<0.05) the amount of TBARS generated by the Fe2+/ascorbate system by 85.3,
      86.4, 86.0, 86.1, 86.0, 86.0 and 86.0% and 86.7, 81.3, 81.3, 80, 80, 82.6 and
      83.1%, respectively. Similarly, quercetin, a standard antioxidant, was found to
      induce an 80% reduction in the amount of TBARS produced. The same IC50 value of
      0.025 mM was observed for robustaside B, para-hydroxyphenol and quercetin. Pre
      incubation of varying concentrations of robustaside B (0.125, 0.2, 0.5 and 1 mM)
      with succinate-energized mitochondria induced MMPT pore opening by 0, -33.3, 
      59.3 and -218.5%, compared with control mitochondria. Para-hydroxyphenol at 0.1,
      0.2, 0.25 and 0.5 mM induced MMPT pore opening in a concentration-dependent
      manner up to 0.25 mM by -21, -54.4 and -107.0%, respectively. Quercetin at 0.05,
      0.1, 0.25, 0.5, 0.75 and 1 mM also induced MMPT pore opening in the absence of
      calcium in a concentration-dependent manner by 5, 3.7, -42.6, -81.5, -187 and 
      161.1%, respectively. The current observations confirm the antioxidant properties
      of robustaside B and para-hydroxyphenol, and indicate a potential therapeutic use
      of the compounds for the treatment of diseases requiring the induction of cell
      death, including cancer.

PMID- 24026540
TI  - Unexpected toxicity of cetuximab combined with conventional chemoradiotherapy in
      patients with locally advanced anal cancer: results of the UNICANCER ACCORD 16
      phase II trial.
AB  - BACKGROUND: The ACCORD 16 phase II trial aimed to evaluate the objective response
      rate after combination of conventional chemoradiotherapy (CRT) and cetuximab in
      locally advanced anal canal carcinoma (LAACC). PATIENTS AND METHODS:
      Immunocompetent patients with histologically confirmed LAACC received CRT [45
      gray (Gy)] in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks
      1 and 5), in combination with weekly dose of cetuximab (250 mg/m(2) with a
      loading dose of 400 mg/m(2) 1 week before irradiation), and a standard dose boost
      (20 Gy). The trial was originally designed to include 81 patients to detect a 15%
      of objective response increase with the new combination in comparison with CRT.
      RESULTS: The trial was prematurely stopped after the declaration of 15 serious
      adverse events (SAEs) in 14 out of 16 patients. Five patients received the entire
      planned treatment, and the compliance was higher after amendments of the
      protocol. Among the 15 SAEs, 6 were unexpected. Grade (G) 3/4 acute toxic
      effects, observed in 88% patients, were general (n = 13, 81%), digestive (n = 9,
      56%), dermatological (n = 5, 31%), infectious (n = 4, 25%), haematological (n =
      3, 19%), and others (n = 9); and three patients suffered from six G3/4 late toxic
      effects. No treatment-related death was reported. All 11 assessable patients had
      an objective response consisting of six complete (55%) and five partial (45%)
      response 2 months after the end of the treatment. Thirteen patients were followed
      up with a median of 22 months [95% confidence interval (CI ): 18-27] and had a 1
      year colostomy-free survival, progression-free and overall survival rate of 67%
      (95% CI: 40%-86%), 62% (95% CI: 36%-82%), and 92% (95% CI: 67%-99%),
      respectively. CONCLUSION: CRT plus cetuximab was unacceptably toxic in this
      population of patients. Results of others phase II trials evaluating this
      combination are awaited to confirm these findings. EUDRA CT NO: 2007-007029-38.

PMID- 24026542
TI  - Feasibility of closed-loop insulin delivery in type 2 diabetes: a randomized
      controlled study.
AB  - OBJECTIVE: Closed-loop insulin delivery offers a promising treatment option, but
      to date, it has only been evaluated in type 1 diabetes. Our aim was to evaluate
      the feasibility of fully closed-loop subcutaneous insulin delivery in insulin
      naive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Twelve subjects
      (seven males, age 57.2 years, BMI 30.5 kg/m2) with noninsulin-treated type 2
      diabetes (HbA1c 8.4% [68 mmol/mol], diabetes duration 7.6 years) underwent two 24
      h visits (closed-loop and control) in a randomized crossover design. During
      closed-loop visits, the subjects' routine diabetes therapy was replaced with
      model predictive control algorithm-driven subcutaneous insulin pump delivery
      based on real-time continuous glucose monitoring. Meals were unannounced, and no
      additional insulin was administered for carbohydrates consumed. During control
      visits, the usual diabetes regimen was continued (metformin 92%, sulfonylureas
      58%, dipeptidyl peptidase-4 inhibitors 33%). On both visits, subjects consumed
      matched 50- to 80-g carbohydrate meals and optional 15-g carbohydrate snacks and
      remained largely sedentary. Plasma glucose measurements evaluated closed-loop
      performance. RESULTS: Compared with conventional therapy, 24 h of closed-loop
      insulin delivery increased overall the median time in target plasma glucose (3.9
      8.0 mmol/L) from 24 to 40% (P = 0.016), despite sensor under-reading by a median
      of 1.2 mmol/L. The benefit of the closed-loop system was more prominent
      overnight, with greater time in target glucose (median 78 vs. 35%; P = 0.041) and
      less time in hyperglycemia (22 vs. 65%; P = 0.041). There was no hypoglycemia
      during either intervention. CONCLUSIONS: A closed-loop system without meal
      announcement and using subcutaneous insulin delivery in insulin-naive patients
      with type 2 diabetes appears feasible and safe. Improvement in postprandial
      glucose control may require further optimization of system performance.

PMID- 24026543
TI  - Differences in the management of type 1 diabetes among adults under excellent
      control compared with those under poor control in the T1D Exchange Clinic
      Registry.
AB  - OBJECTIVE: Optimizing glycemic control in type 1 diabetes is important to
      minimize the risk of complications. We used the large T1D Exchange clinic
      registry database to identify characteristics and diabetes management techniques
      in adults with type 1 diabetes, differentiating those under excellent glycemic
      control from those with poorer control. RESEARCH DESIGN AND METHODS: The cross
      sectional analysis included 627 participants with HbA1c <6.5% (excellent control)
      and 1,267 with HbA1c >=8.5% (fair/poor control) at enrollment who were >=26 years
      of age (mean +/- SD 45.9 +/- 13.2 years), were not using continuous glucose
      monitoring, and had type 1 diabetes for >=2 years (22.8 +/- 13.0 years). RESULTS:
      Compared with the fair/poor control group, participants in the excellent control
      group had higher socioeconomic status, were more likely to be older and married,
      were less likely to be overweight, were more likely to exercise frequently, and
      had lower total daily insulin dose per kilogram (P < 0.0001 for each). Excellent
      control was associated with more frequent self-monitoring of blood glucose
      (SMBG), giving mealtime boluses before a meal rather than at the time of or after
      a meal, performing SMBG before giving a bolus, and missing an insulin dose less
      frequently (P < 0.0001 for each). Frequency of severe hypoglycemia was similar
      between groups, whereas diabetic ketoacidosis was more common in the fair/poor
      control group. CONCLUSIONS: Diabetes self-management related to insulin delivery,
      glucose monitoring, and lifestyle tends to differ among adults with type 1
      diabetes under excellent control compared with those under poorer control. Future
      studies should focus on modifying diabetes management skills in adult type 1
      diabetes patients with suboptimal glycemic control.

PMID- 24026544
TI  - Is neighborhood green space associated with a lower risk of type 2 diabetes?
      Evidence from 267,072 Australians.
AB  - OBJECTIVE Lifestyle interventions for type 2 diabetes mellitus (T2DM) are best
      positioned for success if participants live in supportive neighborhood
      environments. Deprived neighborhoods increase T2DM risk. Parks and other "green
      spaces" promote active lifestyles and therefore may reduce T2DM risk. We
      investigated association between neighborhood green space and the risk of T2DM in
      a large group of adult Australians. RESEARCH DESIGN AND METHODS Multilevel logit
      regression was used to fit associations between medically diagnosed T2DM and
      green space exposure among 267,072 participants in the 45 and Up Study. Green
      space data were obtained from the Australian Bureau of Statistics, and exposure
      was calculated using a 1-km buffer from a participant's place of residence. Odds
      ratios (ORs) were controlled for measures of demographic, cultural, health, diet,
      active lifestyles, socioeconomic status, and neighborhood circumstances. RESULTS
      The rate of T2DM was 9.1% among participants in neighborhoods with 0-20% green
      space, but this rate dropped to approximately 8% for participants with over 40%
      green space within their residential neighborhoods. The risk of T2DM was
      significantly lower in greener neighborhoods, controlling for demographic and
      cultural factors, especially among participants residing in neighborhoods with 41
      60% green space land use (OR 0.87; 95% CI 0.83-0.92). This association was
      consistent after controlling for other explanatory variables and did not vary
      according to neighborhood circumstances. CONCLUSIONS People in greener
      surroundings have a lower risk of T2DM. Planning, promoting, and maintaining
      local green spaces is important in multisector initiatives for addressing the
      T2DM epidemic. 

PMID- 24026545
TI  - Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in
      men: the Kuopio Ischemic Heart Disease Risk Factor study.
AB  - OBJECTIVE The relationship between fish or omega-3 polyunsaturated fatty acids
      (PUFAs) and type 2 diabetes is inconclusive. Even contaminants in fish, such as
      mercury, may modify the effects. We investigated the associations between serum
      omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA),
      docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), hair mercury, and risk of
      incident type 2 diabetes in middle-aged and older Finnish men. RESEARCH DESIGN
      AND METHODS A total of 2,212 men from the prospective, population-based Kuopio
      Ischemic Heart Disease Risk Factor study, aged 42-60 years and free of type 2
      diabetes at baseline in 1984-1989, were investigated. Serum PUFA and hair mercury
      were used as biomarkers for exposure. Dietary intakes were assessed with 4-day
      food recording. Type 2 diabetes was assessed by self-administered questionnaires
      and fasting and 2-h oral glucose tolerance test blood glucose measurement at re
      examination rounds 4, 11, and 20 years after the baseline and by record linkage
      to hospital discharge registry and reimbursement register on diabetes medication
      expenses. Cox proportional hazards models were used to analyze associations.
      RESULTS During the average follow-up of 19.3 years, 422 men developed type 2
      diabetes. Men in the highest versus the lowest serum EPA + DPA + DHA quartile had
      33% lower multivariate-adjusted risk for type 2 diabetes (95% CI 13-49; P trend
      0.01). No statistically significant associations were observed with serum or
      dietary ALA, dietary fish or EPA + DHA, or hair mercury. CONCLUSIONS Serum long
      chain omega-3 PUFA concentration, an objective biomarker for fish intake, was
      associated with long-term lower risk of type 2 diabetes. 

PMID- 24026546
TI  - Islet transplantation stabilizes hemostatic abnormalities and cerebral metabolism
      in individuals with type 1 diabetes.
AB  - OBJECTIVE Islets after kidney transplantation have been shown to positively
      affect the quality of life of individuals with type 1 diabetes (T1D) by reducing
      the burden of diabetes complications, but fewer data are available for islet
      transplantation alone (ITA). The aim of this study was to assess whether ITA has
      a positive impact on hemostatic and cerebral abnormalities in individuals with
      T1D. RESEARCH DESIGN AND METHODS Prothrombotic factors, platelet
      function/ultrastructure, and cerebral morphology, metabolism, and function have
      been investigated over a 15-month follow-up period using ELISA/electron
      microscopy and magnetic resonance imaging, nuclear magnetic resonance
      spectroscopy, and neuropsychological evaluation (Profile of Mood States test and
      paced auditory serial addition test) in 22 individuals with T1D who underwent ITA
      (n = 12) or remained on the waiting list (n = 10). Patients were homogeneous with
      regard to metabolic criteria, hemostatic parameters, and cerebral
      morphology/metabolism/function at the time of enrollment on the waiting list.
      RESULTS At the 15-month follow-up, the group undergoing ITA, but not individuals
      with T1D who remained on the waiting list, showed 1) improved glucose metabolism;
      2) near-normal platelet activation and prothrombotic factor levels; 3) near
      normal cerebral metabolism and function; and 4) a near-normal neuropsychological
      test. CONCLUSIONS ITA, despite immunosuppressive therapy, is associated with a
      near-normalization of hemostatic and cerebral abnormalities. 

PMID- 24026547
TI  - Cost-effectiveness of MODY genetic testing: translating genomic advances into
      practical health applications.
AB  - OBJECTIVE To evaluate the cost-effectiveness of a genetic testing policy for
      HNF1A-, HNF4A-, and GCK-MODY in a hypothetical cohort of type 2 diabetic patients
      25-40 years old with a MODY prevalence of 2%. RESEARCH DESIGN AND METHODS We used
      a simulation model of type 2 diabetes complications based on UK Prospective
      Diabetes Study data, modified to account for the natural history of disease by
      genetic subtype to compare a policy of genetic testing at diabetes diagnosis
      versus a policy of no testing. Under the screening policy, successful
      sulfonylurea treatment of HNF1A-MODY and HNF4A-MODY was modeled to produce a
      glycosylated hemoglobin reduction of -1.5% compared with usual care. GCK-MODY
      received no therapy. Main outcome measures were costs and quality-adjusted life
      years (QALYs) based on lifetime risk of complications and treatments, expressed
      as the incremental cost-effectiveness ratio (ICER) (USD/QALY). RESULTS The
      testing policy yielded an average gain of 0.012 QALYs and resulted in an ICER of
      205,000 USD. Sensitivity analysis showed that if the MODY prevalence was 6%, the
      ICER would be ~50,000 USD. If MODY prevalence was >30%, the testing policy was
      cost saving. Reducing genetic testing costs to 700 USD also resulted in an ICER
      of ~50,000 USD. CONCLUSIONS Our simulated model suggests that a policy of testing
      for MODY in selected populations is cost-effective for the U.S. based on
      contemporary ICER thresholds. Higher prevalence of MODY in the tested population
      or decreased testing costs would enhance cost-effectiveness. Our results make a
      compelling argument for routine coverage of genetic testing in patients with high
      clinical suspicion of MODY.

PMID- 24026548
TI  - Diabetic autonomic neuropathy affects symptom generation and brain-gut axis.
AB  - OBJECTIVE: Long-term diabetes leads to severe peripheral, autonomous, and central
      neuropathy in combination with clinical gastrointestinal symptoms. The brain-gut
      axis thus expresses a neurophysiological profile, and heart rate variability
      (HRV) can be correlated with clinical gastrointestinal symptoms. RESEARCH DESIGN
      AND METHODS: Fifteen healthy volunteers and 15 diabetic patients (12 with type 1
      diabetes) with severe gastrointestinal symptoms and clinical suspicion of
      autonomic neuropathy were included. Psychophysics and evoked brain potentials
      were assessed after painful rectosigmoid electrostimulations, and brain activity
      was modeled by brain electrical source analysis. Self-reported gastrointestinal
      symptoms (per the Patient Assessment of Upper Gastrointestinal Disorder Severity
      Symptom Index) and quality of life (SF-36 Short Form Survey) were collected.
      RESULTS: Diabetic patients had autonomous neuropathy, evidenced by decreased
      electrocardiographic R-R interval (P = 0.03) and lower HRV (P = 0.008). Patients
      were less sensitive to painful stimulation (P = 0.007), had prolonged latencies
      of evoked potentials (P <= 0.001), and showed diminished amplitude of the N2-P2
      component in evoked potentials (P = 0.01). There was a caudoanterior shift of the
      insular brain source (P = 0.01) and an anterior shift of the cingulate generator
      (P = 0.01). Insular source location was associated with HRV assessments (all P <
      0.02), and the shift (expressed in mm) correlated negatively with physical health
      (P < 0.001) and positively with nausea (P = 0.03) and postprandial fullness (P =
      0.03). Cingulate source shift was correlated negatively with physical health (P =
      0.005) and positively with postprandial fullness (P <= 0.001). CONCLUSIONS: This
      study provides evidence for interaction between autonomic neuropathy and
      peripheral nervous degeneration, as well as changes in dipole sources in diabetic
      patients with gastrointestinal symptoms. The findings may lead to improved
      treatment modalities targeting pharmacological neuroprotection or
      neuromodulation.

PMID- 24026549
TI  - Hepatic insulin clearance is closely related to metabolic syndrome components.
AB  - OBJECTIVE: Insulin clearance is decreased in type 2 diabetes mellitus (T2DM) for
      unknown reasons. Subjects with metabolic syndrome are hyperinsulinemic and have
      an increased risk of T2DM. We aimed to investigate the relationship between
      hepatic insulin clearance (HIC) and different components of metabolic syndrome
      and tested the hypothesis that HIC may predict the risk of metabolic syndrome.
      RESEARCH DESIGN AND METHODS: Individuals without diabetes from the Metabolic
      Syndrome Berlin Brandenburg (MeSyBePo) study (800 subjects with the baseline
      examination and 189 subjects from the MeSyBePo recall study) underwent an oral
      glucose tolerance test (OGTT) with assessment of insulin secretion (insulin
      secretion rate [ISR]) and insulin sensitivity. Two indices of HIC were
      calculated. RESULTS: Both HIC indices showed lower values in subjects with
      metabolic syndrome (P < 0.001) at baseline. HIC indices correlate inversely with
      waist circumference, diastolic blood pressure, fasting glucose, triglycerides,
      and OGTT-derived insulin secretion index. During a mean follow-up of 5.1 +/- 0.9
      years, 47 individuals developed metabolic syndrome and 33 subjects progressed to
      impaired glucose metabolism. Both indices of HIC showed a trend of an association
      with increased risk of metabolic syndrome (HICC-peptide odds ratio 1.13 [95% CI
      0.97-1.31], P = 0.12, and HICISR 1.38 [0.88-2.17], P = 0.16) and impaired glucose
      metabolism (HICC-peptide 1.12 [0.92-1.36], P = 0.26, and HICISR 1.31 [0.74-2.33]
      P = 0.36), although point estimates reached no statistical significance.
      CONCLUSIONS: HIC was associated with different components of metabolic syndrome
      and markers of insulin secretion and insulin sensitivity. Decreased HIC may
      represent a novel pathophysiological mechanism of the metabolic syndrome, which
      may be used additionally for early identification of high-risk subjects.

PMID- 24026550
TI  - Conduction slowing in diabetic sensorimotor polyneuropathy.
AB  - OBJECTIVE: Mild demyelination may contribute more to the pathophysiology of nerve
      fiber injury in diabetic sensorimotor polyneuropathy (DSP) than previously
      thought. We investigated the clinical and electrodiagnostic classifications of
      nerve injury in diabetic patients to detect evidence of conduction slowing in
      DSP. RESEARCH DESIGN AND METHODS: Type 1 diabetic subjects (n = 62) and type 2
      diabetic subjects (n = 111) with a broad spectrum of DSP underwent clinical
      examination and nerve conduction studies (NCS). Patients were classified as
      having axonal (group A), conduction slowing (group D), or combined (group C) DSP
      based on electrodiagnostic criteria. Patients with chronic immune-mediated
      neuropathies were not included. The groups were compared using ANOVA, contingency
      tables, and Kruskal-Wallis analyses. RESULTS: Of the 173 type 1 and type 2
      diabetic subjects with a mean age of 59.1 +/- 13.6 years and hemoglobin A1c
      (HbA1c) of 8.0 +/- 1.8% (64 +/- 19.7 mmol/mol), 46% were in group A, 32% were in
      group D, and 22% were in group C. The severity of DSP increased across groups A,
      D, and C, respectively, based on clinical and NCS parameters. The mean HbA1c for
      group D subjects (8.9 +/- 2.3% [74 +/- 25.1 mmol/mol]) was higher than for group
      A and group C subjects (7.7 +/- 1.4% [61 +/- 15.3 mmol/mol] and 7.5 +/- 1.3% [58
      +/- 14.2 mmol/mol]; P = 0.003), and this difference was observed in those with
      type 1 diabetes. CONCLUSIONS: The presence of conduction slowing in patients with
      suboptimally controlled type 1 diabetes indicates the possibility that this stage
      of DSP may be amenable to intervention via improved glycemic control.

PMID- 24026551
TI  - Early diabetic nephropathy: a complication of reduced insulin sensitivity in type
      1 diabetes.
AB  - OBJECTIVE: Diabetic nephropathy (DN) is a major cause of mortality in type 1
      diabetes. Reduced insulin sensitivity is a well-documented component of type 1
      diabetes. We hypothesized that baseline insulin sensitivity would predict
      development of DN over 6 years. RESEARCH DESIGN AND METHODS: We assessed the
      relationship between insulin sensitivity at baseline and development of early
      phenotypes of DN-microalbuminuria (albumin-creatinine ratio [ACR] >=30 mg/g) and
      rapid renal function decline (glomerular filtration rate [GFR] loss >3
      mL/min/1.73 m2 per year)-with three Chronic Kidney Disease Epidemiology
      Collaboration (CKD-EPI) equations over 6 years. Subjects with diabetes (n = 449)
      and without diabetes (n = 565) in the Coronary Artery Calcification in Type 1
      Diabetes study had an estimated insulin sensitivity index (ISI) at baseline and 6
      year follow-up. RESULTS: The ISI was lower in subjects with diabetes than in
      those without diabetes (P < 0.0001). A higher ISI at baseline predicted a lower
      odds of developing an ACR >=30 mg/g (odds ratio 0.65 [95% CI 0.49-0.85], P =
      0.003) univariately and after adjusting for HbA1c (0.69 [0.51-0.93], P = 0.01). A
      higher ISI at baseline conferred protection from a rapid decline of GFR as
      assessed by CKD-EPI cystatin C (0.77 [0.64-0.92], P = 0.004) and remained
      significant after adjusting for HbA1c and age (0.80 [0.67-0.97], P = 0.02). We
      found no relation between ISI and rapid GFR decline estimated by CKD-EPI
      creatinine (P = 0.38) or CKD-EPI combined cystatin C and creatinine (P = 0.50).
      CONCLUSIONS: Over 6 years, a higher ISI independently predicts a lower odds of
      developing microalbuminuria and rapid GFR decline as estimated with cystatin C,
      suggesting a relationship between insulin sensitivity and early phenotypes of DN.

PMID- 24026552
TI  - Association between sleep duration and diabetes in black and white adults.
AB  - OBJECTIVE: To examine racial differences in sleep duration and its relationship
      with diabetes. RESEARCH DESIGN AND METHODS: We used data from a nationally
      representative sample of U.S. adults (n = 130,943) participating in the National
      Health Interview Survey from 2004 to 2011. Usual sleep duration was self-reported
      and categorized as <7 h (short), 7 h (optimal), and >7 h (long). Diabetes status
      was based on self-reported diagnosis from a health professional. RESULTS:
      Participants' mean age was 50.6 years, 49% were men, and 13% were black. Compared
      with whites, blacks were more likely to report short sleep (37 vs. 28%) and less
      likely to get 7 h of sleep (24 vs. 33%). Diabetes (9,643 cases [9%] in whites and
      3,612 cases [15%] in blacks) had a U-shaped distribution with sleep in whites
      (10, 7, and 9%, for short, optimal, and long sleep, respectively) and blacks (16,
      13, and 15%). Suboptimal sleep duration was more strongly associated with
      diabetes in whites than in blacks among short (prevalence ratio 1.49 [95% CI 1.40
      1.58] vs. 1.21 [1.09-1.34]) and long (1.32 [1.25-1.40] vs. 1.11 [1.00-1.23])
      sleepers on the relative scale. Adjustment for socioeconomic status (SES)
      attenuated the short sleep-diabetes association in blacks (1.15 [1.02-1.29]), and
      the racial/ethnic difference in the short sleep-diabetes association became
      nonsignificant after SES adjustments. CONCLUSIONS: Suboptimal sleep duration was
      positively associated with diabetes in blacks and whites, although diabetes
      prevalence was higher at any level of sleep in blacks. Socioeconomic factors
      appear to partly explain the association for short sleep in blacks as well as
      disparity between racial groups.

PMID- 24026553
TI  - Dairy consumption, type 2 diabetes, and changes in cardiometabolic traits: a
      prospective cohort study of middle-aged and older Chinese in Beijing and
      Shanghai.
AB  - OBJECTIVE To prospectively investigate associations of dairy consumption with
      risk of type 2 diabetes and changes of cardiometabolic traits. RESEARCH DESIGN
      AND METHODS In 2005, 2,091 middle-aged and older Chinese men and women were
      recruited and followed for 6 years. Baseline dairy consumption was assessed by a
      74-item food frequency questionnaire. Erythrocyte fatty acids were analyzed by
      gas chromatography coupled with flame ion detector. Cardiometabolic traits were
      measured at both baseline and follow-up visits. RESULTS Only 1,202 (57.5%)
      participants reported any dairy consumption, with a median intake of 0.89
      (interquartile range 0.19-1.03) serving/day. Compared with nonconsumers, the
      relative risks (RRs) of type 2 diabetes among those having 0.5-1 serving/day and
      >1 serving/day were 0.70 (95% CI 0.55-0.88) and 0.65 (0.49-0.85), respectively,
      after multivariate adjustment (Ptrend < 0.001), which were attenuated by further
      adjusting for changes in glucose during follow-up (Ptrend = 0.07). Total dairy
      consumption was associated with favorable changes in glucose, waist
      circumference, BMI, diastolic blood pressure (all Ptrend < 0.05), and systolic
      blood pressure (Ptrend = 0.05) after multivariate adjustment, including baseline
      values of dependent variables. Erythrocyte trans-18:1 isomers were significantly
      correlated with total dairy consumption (rs = 0.37, Ptrend < 0.001), and these
      dairy food biomarkers were associated with a lower risk of type 2 diabetes. The
      RR of type 2 diabetes comparing extreme quartiles of trans-18:1 isomers was 0.82
      (0.65-1.04, Ptrend = 0.02), which was attenuated after adjustment for dairy
      consumption (Ptrend = 0.15). CONCLUSIONS Dairy consumption was associated with a
      significantly lower risk of type 2 diabetes and favorable changes of
      cardiometabolic traits in Chinese. 

PMID- 24026555
TI  - A prediction model for adverse outcome in hospitalized patients with diabetes.
AB  - OBJECTIVE: There are no formal prognostic models predicting adverse outcomes
      (excessive length of stay or mortality) in hospitalized patients with diabetes.
      In this study, we aimed to develop a prediction model that will help identify
      patients with diabetes who are most likely to have an adverse event during their
      hospital stay. RESEARCH DESIGN AND METHODS: Analysis was based on 25,118
      admissions with diabetes to University Hospital Birmingham, Birmingham, U.K.,
      over 4 years (2007-2010). Adverse events are defined as either excessive length
      of stay or inpatient mortality. Key predictors were variables that are often
      available in the first 72 h of admission and included demographic
      characteristics, clinical pathological test results, and use of insulin. Models
      were constructed using logistic regression, discrimination and calibration was
      assessed, and internal validation was carried out. RESULTS: The model performed
      well with an area under the curve (AUC) of 0.802 with only a mild reduction being
      noted in the internal validation (AUC 0.798). At a cutoff value of 25%
      probability of having an adverse outcome the sensitivity was 76%, specificity was
      70%, and the positive predictive value was 49%. If it is used for a case-finding
      approach limiting to noncritical care settings, then at the same cutoff value,
      two-thirds (sensitivity 69%) of the admissions with adverse outcomes could
      potentially be identified. CONCLUSIONS: Once externally validated, we suggest
      that our model will be a useful tool for identifying diabetic patients who are at
      risk for poor outcomes when admitted to hospital.

PMID- 24026554
TI  - Correlates of treatment patterns among youth with type 2 diabetes.
AB  - OBJECTIVE To describe treatment regimens in youth with type 2 diabetes and
      examine associations between regimens, demographic and clinical characteristics,
      and glycemic control. RESEARCH DESIGN AND METHODS This report includes 474 youth
      with a clinical diagnosis of type 2 diabetes who completed a SEARCH for Diabetes
      in Youth study visit. Diabetes treatment regimen was categorized as lifestyle
      alone, metformin monotherapy, any oral hypoglycemic agent (OHA) other than
      metformin or two or more OHAs, insulin monotherapy, and insulin plus any OHA(s).
      Association of treatment with demographic and clinical characteristics (fasting C
      peptide [FCP], diabetes duration, and self-monitoring of blood glucose [SMBG]),
      and A1C was assessed by chi(2) and ANOVA. Multiple linear regression models were
      used to evaluate independent associations of treatment regimens and A1C,
      adjusting for demographics, diabetes duration, FCP, and SMBG. RESULTS Over 50% of
      participants reported treatment with metformin alone or lifestyle. Of the
      autoantibody-negative youth, 40% were on metformin alone, while 33% were on
      insulin-containing regimens. Participants on metformin alone had a lower A1C (7.0
      +/- 2.0%, 53 +/- 22 mmol/mol) than those on insulin alone (9.2 +/- 2.7%, 77 +/-
      30 mmol/mol) or insulin plus OHA (8.6 +/- 2.6%, 70 +/- 28 mmol/mol) (P < 0.001).
      These differences remained significant after adjustment (7.5 +/- 0.3%, 58 +/- 3
      mmol/mol; 9.1 +/- 0.4%, 76 +/- 4 mmol/mol; and 8.6 +/- 0.4%, 70 +/- 4 mmol/mol)
      (P < 0.001) and were more striking in those with diabetes for >=2 years (7.9 +/-
      2.8, 9.9 +/- 2.8, and 9.8 +/- 2.6%). Over one-half of those on insulin-containing
      therapies still experience treatment failure (A1C >=8%, 64 mmol/mol). CONCLUSIONS
      Approximately half of youth with type 2 diabetes were managed with lifestyle or
      metformin alone and had better glycemic control than individuals using other
      therapies. Those with longer diabetes duration in particular commonly experienced
      treatment failures, and more effective management strategies are needed. 

PMID- 24026556
TI  - Methylmercury exposure and incident diabetes in U.S. men and women in two
      prospective cohorts.
AB  - OBJECTIVE: Emerging in vitro and animal evidence suggests that methylmercury
      could increase type 2 diabetes, but little evidence exists in humans. We aimed to
      prospectively determine associations of mercury exposure, as assessed by
      biomarker measurement, with incident diabetes. RESEARCH DESIGN AND METHODS: We
      used neutron activation analysis to measure toenail mercury, an objective
      biomarker of methylmercury exposure, in 9,267 adults free of diabetes at baseline
      in two separate U.S. prospective cohorts. Incident diabetes was identified from
      biennial questionnaires and confirmed by validated supplementary questionnaire
      using symptoms, diagnostic tests, and medical therapy. Associations of mercury
      exposure with incident diabetes were assessed using Cox proportional hazards.
      RESULTS: During mean +/- SD follow-up of 19.7 +/- 7.0 years, 1,010 new cases of
      diabetes were diagnosed. The 95th percentile of toenail mercury was 1.32 MUg/g in
      men and 0.76 MUg/g in women, corresponding to exposures ~3.5-fold and 2-fold
      higher than the U.S. Environmental Protection Agency reference dose. In
      multivariable analyses, toenail mercury concentrations were not associated with
      higher incidence of diabetes in women, men, or both cohorts combined. Comparing
      the highest to lowest quintile of exposure, the hazard ratio (95% CI) for
      incident diabetes was 0.86 (0.66-1.11) in women, 0.69 (0.42-1.15) in men, and
      0.77 (0.61-0.98) in the combined cohorts. Findings were similar when more extreme
      categories (deciles) of mercury were compared, and in analyses stratified by fish
      or omega-3 consumption, BMI, and age. CONCLUSIONS: These findings from two
      separate large prospective cohorts do not support adverse effects of
      methylmercury on development of diabetes in men or women at usual levels of
      exposure seen in these populations.

PMID- 24026557
TI  - Small- and large-fiber neuropathy after 40 years of type 1 diabetes: associations
      with glycemic control and advanced protein glycation: the Oslo Study.
AB  - OBJECTIVE: To study large- and small-nerve fiber function in type 1 diabetes of
      long duration and associations with HbA1c and the advanced glycation end products
      (AGEs) N-epsilon-(carboxymethyl)lysine (CML) and methylglyoxal-derived
      hydroimidazolone. RESEARCH DESIGN AND METHODS: In a long-term follow-up study, 27
      persons with type 1 diabetes of 40 +/- 3 years duration underwent large-nerve
      fiber examinations, with nerve conduction studies at baseline and years 8, 17,
      and 27. Small-fiber functions were assessed by quantitative sensory thresholds
      (QST) and intraepidermal nerve fiber density (IENFD) at year 27. HbA1c was
      measured prospectively through 27 years. Serum CML was measured at year 17 by
      immunoassay. Serum hydroimidazolone was measured at year 27 with liquid
      chromatography-mass spectrometry. RESULTS: Sixteen patients (59%) had large-fiber
      neuropathy. Twenty-two (81%) had small-fiber dysfunction by QST. Heat pain
      thresholds in the foot were associated with hydroimidazolone and HbA1c. IENFD was
      abnormal in 19 (70%) and significantly lower in diabetic patients than in age
      matched control subjects (4.3 +/- 2.3 vs. 11.2 +/- 3.5 mm, P < 0.001). IENFD
      correlated negatively with HbA1c over 27 years (r = -0.4, P = 0.04) and CML (r = 
      0.5, P = 0.01). After adjustment for age, height, and BMI in a multiple linear
      regression model, CML was still independently associated with IENFD. CONCLUSIONS:
      Small-fiber sensory neuropathy is a major manifestation in type 1 diabetes of 40
      years duration and more prevalent than large-fiber neuropathy. HbA1c and the AGEs
      CML and hydroimidazolone are important risk factors in the development of large-
      and small-fiber dysfunction in long-term type 1 diabetes.

PMID- 24026558
TI  - Prediction of retinopathy at 20 years after onset in younger-onset type 1
      diabetes using mean metabolic memory-free HbA1c values: the importance of using
      HbA1c data of total, not partial, diabetes duration.
AB  - OBJECTIVE: Metabolic memory, in which past hyperglycemia could affect future
      retinopathy, is a potential issue in studying the relationship between glycemia
      and retinopathy. We examined retrospectively if mean "metabolic memory-free"
      glycosylated hemoglobin A1C (HbA1c) values covering total diabetes duration could
      predict retinopathy in younger-onset type 1 diabetes mellitus (T1DM). RESEARCH
      DESIGN AND METHODS: Inclusion criteria were T1DM onset before age 30 years, first
      visit to our center between 1988 and 1990 soon after onset, continuous HbA1c data
      for 20 years, and a 20-year follow-up retinopathy examination. Retinopathy
      predictive capabilities of HbA1c variables were examined. RESULTS: Of 15
      subjects, 5 were retinopathy-positive and 10 were retinopathy-negative at the 20
      year follow-up. Mean metabolic memory-free HbA1c values for the 20 years showed a
      substantial capacity to predict retinopathy at 20 years. The longer the period
      without HbA1c data following onset in simulation, the less accurate the
      prediction. CONCLUSIONS: HbA1c values may predict retinopathy better if metabolic
      memory-free data are used.

PMID- 24026559
TI  - Glycerol and fatty acids in serum predict the development of hyperglycemia and
      type 2 diabetes in Finnish men.
AB  - OBJECTIVE: We investigated the association of fasting serum glycerol and fatty
      acids (FAs) as predictors for worsening of hyperglycemia and incident type 2
      diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional and longitudinal analyses
      of the population-based METabolic Syndrome in Men (METSIM) Study included 9,398
      Finnish men (mean age 57 +/- 7 years). At baseline, levels of serum glycerol,
      free FAs (FFAs), and serum FA profile, relative to total FAs, were measured with
      proton nuclear magnetic resonance spectroscopy. RESULTS: At baseline, levels of
      glycerol, FFAs, monounsaturated FAs, saturated FAs, and monounsaturated n-7 and 
      9 FAs, relative to total FAs, were increased in categories of fasting and 2-h
      hyperglycemia, whereas the levels of n-3 and n-6 FAs, relative to total FAs,
      decreased (N = 9,398). Among 4,335 men with 4.5-year follow-up data available,
      276 developed type 2 diabetes. Elevated levels of glycerol, FFAs, monounsaturated
      FAs, and saturated and monounsaturated n-7 and -9 FAs, relative to total FAs,
      predicted worsening of hyperglycemia and development of incident type 2 diabetes
      after adjustment for confounding factors. n-6 FAs, mainly linoleic acid (LA),
      relative to total FAs, were associated with reduced risk for the worsening of
      hyperglycemia and conversion to type 2 diabetes. CONCLUSIONS: Our large
      population-based study shows that fasting serum levels of glycerol, FFAs,
      monounsaturated FAs, saturated FAs, and n-7 and -9 FAs are biomarkers for an
      increased risk of development of hyperglycemia and type 2 diabetes, whereas high
      levels of serum n-6 FAs, reflecting dietary intake of LA, were associated with
      reduced risk for hyperglycemia and type 2 diabetes.

PMID- 24026560
TI  - Linagliptin lowers albuminuria on top of recommended standard treatment in
      patients with type 2 diabetes and renal dysfunction.
AB  - OBJECTIVE: Preclinical data suggest that linagliptin, a dipeptidyl peptidase-4
      inhibitor, may lower urinary albumin excretion. The ability of linagliptin to
      lower albuminuria on top of renin-angiotensin-aldosterone system (RAAS)
      inhibition in humans was analyzed by pooling data from four similarly designed,
      24-week, randomized, double-blind, placebo-controlled, phase III trials. RESEARCH
      DESIGN AND METHODS: A pooled analysis of four completed studies identified 217
      subjects with type 2 diabetes and prevalent albuminuria (defined as a urinary
      albumin-to-creatinine ratio [UACR] of 30-3,000 mg/g creatinine) while receiving
      stable doses of RAAS inhibitors. Participants were randomized to either
      linagliptin 5 mg/day (n = 162) or placebo (n= 55). The primary end point was the
      percentage change in geometric mean UACR from baseline to week 24. RESULTS: UACR
      at week 24 was reduced by 32% (95% CI -42 to -21; P < 0.05) with linagliptin
      compared with 6% (95% CI -27 to +23) with placebo, with a between-group
      difference of 28% (95% CI -47 to -2; P = 0.0357). The between-group difference in
      the change in HbA1c from baseline to week 24 was -0.61% (-6.7 mmol/mol) in favor
      of linagliptin (95% CI -0.88 to -0.34% [-9.6 to -3.7 mmol/mol]; P < 0.0001). The
      albuminuria-lowering effect of linagliptin, however, was not influenced by race
      or HbA1c and systolic blood pressure (SBP) values at baseline or after treatment.
      CONCLUSIONS: Linagliptin administered in addition to stable RAAS inhibitors led
      to a significant reduction in albuminuria in patients with type 2 diabetes and
      renal dysfunction. This observation was independent of changes in glucose level
      or SBP. Further research to prospectively investigate the renal effects of
      linagliptin is underway.

PMID- 24026561
TI  - Lower fasting muscle mitochondrial activity relates to hepatic steatosis in
      humans.
AB  - OBJECTIVE: Muscle insulin resistance has been implicated in the development of
      steatosis and dyslipidemia by changing the partitioning of postprandial substrate
      fluxes. Also, insulin resistance may be due to reduced mitochondrial function. We
      examined the association between mitochondrial activity, insulin sensitivity, and
      steatosis in a larger human population. RESEARCH DESIGN AND METHODS: We analyzed
      muscle mitochondrial activity from ATP synthase flux (fATP) and ectopic lipids by
      multinuclei magnetic resonance spectroscopy from 113 volunteers with and without
      diabetes. Insulin sensitivity was assessed from M values using euglycemic
      hyperinsulinemic clamps and/or from oral glucose insulin sensitivity (OGIS) using
      oral glucose tolerance tests. RESULTS: Muscle fATP correlated negatively with
      hepatic lipid content and HbA1c. After model adjustment for study effects and
      other confounders, fATP showed a strong negative correlation with hepatic lipid
      content and a positive correlation with insulin sensitivity and fasting C
      peptide. The negative correlation of muscle fATP with age, HbA1c, and plasma free
      fatty acids was weakened after adjustment. Body mass, muscle lipid contents,
      plasma lipoproteins, and triglycerides did not associate with fATP. CONCLUSIONS:
      The association of impaired muscle mitochondrial activity with hepatic steatosis
      supports the concept of a close link between altered muscle and liver energy
      metabolism as early abnormalities promoting insulin resistance.

PMID- 24026562
TI  - Pulmonary function reduction in diabetes with and without chronic obstructive
      pulmonary disease.
AB  - OBJECTIVE: Diabetes damages major organ systems through disrupted glycemic
      control and increased inflammation. The effects of diabetes on the lung have been
      of interest for decades, but the modest reduction in pulmonary function and its
      nonprogressive nature have limited its investigation. A recent systematic review
      found that diabetes was associated with reductions in forced expiratory volume in
      1 s (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon
      monoxide of the lung and increased FEV1/FVC. They reported pooled results
      including few smokers. This study will examine measures of pulmonary function in
      participants with extensive smoking exposure. RESEARCH DESIGN AND METHODS: We
      examined pulmonary function in participants with a >10-pack-year history of
      smoking with and without diabetes with and without chronic obstructive pulmonary
      disease (COPD). We measured pulmonary function, exercise capacity, and pulmonary
      related quality of life in 10,129 participants in the Genetic Epidemiology of
      Chronic Obstructive Pulmonary Disease (COPDGene) Study. RESULTS: Participants
      with diabetes were observed to have reduced pulmonary function after controlling
      for known risk factors and also significant reductions in exercise capacity and
      quality of life across functional stages of COPD. CONCLUSIONS: Pulmonary function
      in patients with >=10 pack-years of smoking and diabetes is reduced, and this
      decrease is associated with significant reductions in activity-related quality of
      life and exercise capacity.

PMID- 24026564
TI  - Risk for end-stage renal disease over 25 years in the population-based WESDR
      cohort.
AB  - OBJECTIVE: In the population-based Wisconsin Epidemiologic Study of Diabetic
      Retinopathy (WESDR) cohort, we sought to examine whether a decline in the
      prevalence and incidence of end-stage renal disease (ESRD) was evident with
      increasing calendar year of type 1 diabetes diagnosis among people followed for
      25 years. Factors associated with the hazard of incident ESRD that may mediate a
      decline were also investigated. RESEARCH DESIGN AND METHODS: Participants were
      examined at baseline in 1980 (n = 996) and at 4-25 years of follow-up. ESRD was
      defined by self-reported renal transplant or dialysis. Cumulative incidence with
      competing risk of death was determined. Incident ESRD was modeled by period of
      diagnosis, adjusting for other known risk factors using discrete time hazard
      models. RESULTS: When diabetes was diagnosed during 1970-1980, the unadjusted
      cumulative incidence of ESRD at 25 years was 9.3%. The unadjusted hazard of ESRD
      was reduced by 70% (P < 0.001), compared with those diagnosed with diabetes in
      1922-1969; however, the association was attenuated by glycosylated hemoglobin
      level (HbA1c), systolic blood pressure, and antihypertensive use (hazard ratio
      [HR] 0.89 [95% CI 0.55-1.45]). HbA1c, age, and male sex remained associated with
      ESRD hazard after adjustment for kidney function and proliferative retinopathy.
      CONCLUSIONS: A lower incidence of ESRD among those more recently diagnosed with
      type 1 diabetes was explained by improvements in glycemic and blood pressure
      control over the last several decades. Intensive diabetes management, especially
      for glycemic control, remains important even in long-standing diabetes as it may
      delay the development of ESRD.

PMID- 24026563
TI  - B-lymphocyte depletion with rituximab and beta-cell function: two-year results.
AB  - OBJECTIVE: We previously reported that selective depletion of B-lymphocytes with
      rituximab, an anti-CD20 monoclonal antibody, slowed decline of beta-cell function
      in recent-onset type 1 diabetes mellitus (T1DM) at 1 year. Subjects were followed
      further to determine whether there was persistence of effect. RESEARCH DESIGN AND
      METHODS: Eighty-seven subjects (aged 8-40 years) were randomly assigned to, and
      81 received, infusions of rituximab or placebo on days 1, 8, 15, and 22. The
      primary outcome-baseline-adjusted mean 2-h area under the curve (AUC) serum C
      peptide during a mixed-meal tolerance test (MMTT) at 1 year-showed higher C
      peptide AUC with rituximab versus placebo. Subjects were further followed with
      additional MMTTs every 6 months. RESULTS: The rate of decline of C-peptide was
      parallel between groups but shifted by 8.2 months in rituximab-treated subjects.
      Over 30 months, AUC, insulin dose, and HbA1c were similar for rituximab and
      placebo. However, in evaluating change in C-peptide over the entire follow-up
      period, the rituximab group means were significantly larger as compared within
      assessment times with the placebo group means using a global test (P = 0.03).
      Odds ratio for loss of C-peptide to <0.2 nmol/L following rituximab was 0.565 (P
      = 0.064). B-lymphocytes recovered to baseline values by 18 months. Serum IgG
      levels were maintained in the normal range but IgM levels were depressed.
      CONCLUSIONS: Like several other immunotherapeutic approaches tested, in recent
      onset T1DM, rituximab delays the fall in C-peptide but does not appear to
      fundamentally alter the underlying pathophysiology of the disease.

PMID- 24026565
TI  - Quality of life and fecal incontinence after transanal endoscopic microsurgery
      for benign and malignant rectal lesions.
AB  - BACKGROUND: Transanal endoscopic microsurgery (TEM) is a minimally invasive
      treatment used to excise a variety of rectal lesions. Potential overstretching of
      the sphincter's musculature due to dilation of the anal canal to allow placement
      of a 40-mm-wide scope combined with partial resection of the rectum and
      subsequent loss of rectal volume creates a concern regarding anorectal function
      postoperatively. Data regarding patient satisfaction with anorectal function and
      quality of life after TEM are scant. This report presents data on patient
      satisfaction gathered during a period of 10 years. METHODS: A prospectively
      maintained database of patients undergoing TEM from 1997 to 2007 was queried to
      identify patients to survey using the Fecal Incontinence Quality of Life Scale
      questionnaire, the European Organization for Research and Treatment of Cancer
      Quality of Life Questionnaire (EORTC QLQ-C30) questionnaire version 3, and a
      questionnaire designed by the authors to assess satisfaction with quality of
      life. From a group of 86 patients, 57 (66 %) responded to the questionnaires.
      Patient satisfaction outcomes were determined by age, preoperative diagnosis,
      tumor level in the rectum, excision method, and radiation treatment. RESULTS:
      Most of the patients (94.7 %) preferred TEM to having a stoma. Age (p = 0.03) and
      nature of the lesion (p = 0.03) were the only factors that affected coping.
      Depression was affected only by the presence of malignancy (p = 0.001). Excision
      method was the only factor that significantly influenced overall lifestyle (p =
      0.002). Neither tumor level (p = 0.8) nor radiation therapy (p = 0.9) affected
      patient satisfaction with lifestyle after TEM. The presence of malignancy (p =
      0.004) and full-thickness excision (p = 0.02) were related to more problems with
      fecal incontinence. CONCLUSION: Satisfaction with fecal continence generally is
      high after TEM. Tumor level, size of tumor, and radiation therapy do not affect
      the level of satisfaction after TEM. Younger age and benign nature of the lesion
      help patients to cope better with lifestyle changes and reduce depression.
      Patients with submucosal excision have a significantly higher level of
      satisfaction.

PMID- 24026567
TI  - Teriparatide treatment of severe osteoporosis reduces the risk of vertebral
      fractures compared with standard care in routine clinical practice.
AB  - Teriparatide (TPTD) is often used for the treatment of patients with severe
      osteoporosis, but its effectiveness in this patient group has not been
      specifically studied. Here, we report upon the results of an observational study
      involving 323 patients with severe osteoporosis (bone density T-score of -4 or
      less) who were treated at a specialist osteoporosis clinic with TPTD (n = 217) or
      standard care (n = 106) over a 5.5-year period. The standard care group did not
      receive TPTD because they declined to self-inject (59.4%), had a contraindication
      (7.5%), or were already stabilized on oral bisphosphonates (33%). The two groups
      were matched for the severity of osteoporosis, fracture risk, and most other
      clinical variables. The annual percentage change in lumbar spine bone mineral
      density (BMD) was greater in the TPTD group (8.2 +/- 6.0 vs. 5.0 +/- 8.4, p =
      0.002), but there was no difference in response of hip BMD. During follow-up,
      3/217 (1.38%) TPTD-treated patients had new vertebral fractures compared with
      7/106 (6.6%) receiving standard care (p = 0.011), but there was no difference
      between the groups in the rate of nonvertebral fractures (11.1 vs. 8.5%, p =
      0.47). Logistic regression analysis adjusting for baseline characteristics showed
      that the risk of vertebral fractures in TPTD-treated patients was significantly
      reduced compared with standard care (odds ratio = 0.12, 95% confidence interval
      0.03-0.55, p = 0.007). Treatment of severe spinal osteoporosis with TPTD
      substantially reduces the risk of vertebral fractures compared with standard care
      and may be the preferred treatment in this patient group.

PMID- 24026566
TI  - Outcomes of second self-expandable metallic stent insertion for malignant gastric
      outlet obstruction.
AB  - BACKGROUND: Self-expandable metallic stents are used widely to relieve malignant
      gastric outlet obstruction (GOO). However, restenosis or migration of first
      stents is a frequent complication. The purpose of this retrospective cohort study
      was to evaluate the effectiveness of second stents as an approach to manage
      failure of first stents in patients with malignant GOO. METHODS: A total of 222
      patients with gastric cancer received first stents due to inoperable GOO at
      National Cancer Center in Korea between January 2008 and June 2011. Monthly
      follow-up interviews were performed, and second stents (stent-in-stent or stent
      after-migration) were inserted in 59 patients by June 2012. Technical and
      clinical successes and long-term complications were evaluated. RESULTS: The
      technical and immediate clinical success rates were 98.3 % (58/59) and 91.5 %
      (54/59), respectively. Patients who received a second stent due to late
      complications involving the first stent (migration, restenosis, and fracture)
      showed a higher clinical success rate (95.8 % [46/48]) than patients who received
      a second stent due to immediate clinical failure of the first stent (72.7 %
      [8/11], p = 0.04). The immediate clinical success rate of stent-after-migration
      (100 % [11/11]) was not different from that of stent-in-stent (89.6 % [43/48], p
      = 1.0). The stent dysfunction rate of stent-after-migration (27.3 % [3/11]) also
      was similar to that of stent-in-stent (29.2 % [14/48], p = 1.0). The median
      patencies of stent-in-stent and stent-after-migration were 27.4 and 58.4 weeks,
      respectively (p = 0.177). There were no significant prognostic factors for
      patency of second stents. CONCLUSIONS: Insertion of a second stent is effective
      for treating the first-stent failure in gastric cancer patients with GOO,
      especially if the immediate outcome of the first stent was successful.

PMID- 24026568
TI  - Expression of nucleoside transporter in freshly isolated neurons and astrocytes
      from mouse brain.
AB  - Nucleoside transporters comprise equilibrative ENT1-4 and concentrative CNT1-3.
      CNTs transport against an intracellular/extracellular gradient and are essential
      for transmitter removal, independently of metabolic need. ENT1-4 mediate
      transport until intracellular/extracellular equilibrium of the transported
      compound, but are very efficient, when the accumulated nucleoside or nucleobase
      is rapidly eliminated by metabolism. Most nucleoside transporters are membrane
      bound, but ENT3 is mainly intracellular. This study uses freshly isolated neurons
      and astrocytes from two adult mouse strains. In one transgenic strain the
      neuronal marker Thy1 was associated with a compound fluorescing at one
      wavelength, and in the other the astrocytic marker GFAP was associated with a
      compound fluorescent at a different wavelength. Highly purified astrocytic and
      neuronal populations (as determined by presence/absence of cell-specific genes)
      were obtained from these mice by fluorescence-activated cell sorting. In each
      population mRNA analysis was performed by reverse-transcription polymerase chain
      reaction. CNT1 was absent in both cell types; all other nucleoside transporters
      were expressed to at least a similar degree (in relation to applied amount of RNA
      and to a house-keeping gene) in astrocytes as in neurons. Astrocytic ENT3
      enrichment was dramatic, but it was not up-regulated after fluoxetine-mediated
      increase in DNA synthesis. A comparison with results obtained in cultured
      astrocytes shows that the latter are generally compatible with the present
      findings and suggests that many observations obtained in intact tissue, mainly by
      in situ hybridization (which also determines mRNA expression) may underestimate
      astrocytic nucleoside transporter expression.

PMID- 24026570
TI  - Ecological and human health risks from metal(loid)s in peri-urban soil in
      Nanjing, China.
AB  - In order to investigate the ecological and human health risks of metal(loid)s
      (Cu, Pb, Zn, Ni, Cd, Mn, Cr, and As) in peri-urban soils, 43 surface soil samples
      were collected from the peri-urban area around Nanjing, a megacity in China. The
      average contents were 1.19, 67.8, 37.6, 105, 167, 44.6, 722, and 50.8 mg kg(-1)
      for Cd, Cr, Ni, Pb, Zn, Cu, Mn, and As, respectively. A significant positive
      correlation was found between Cu, Pb, Zn, Cd, Mn, and As (p < 0.01), and Cr had a
      significant positive correlation with Ni (p < 0.01). Geoaccumulation indices
      indicate the presence of Cd and As contamination in all of the peri-urban soil
      samples. Potential ecological risk indices show that the metal(loid)s in the soil
      could result in higher ecological risks. Cd is the main contributor to the risk,
      followed by As. The levels of Cu, Pb, Zn, Cd, Mn, and As in stomach and
      intestinal phases show a positive linear correlation with their total contents.
      Mn, Zn, Ni, Cd, and Pb in stomach phase showed higher bioaccessibility, while in
      intestinal phase, Cu, Cr, and As had the higher bioaccessibility. The
      carcinogenic risk in children and adults posed by As, Pb, and Cr via ingestion
      was deemed acceptable. The non-carcinogenic risks posed by these metal(loid)s via
      ingestion to children are higher than to adults and mainly result from As.

PMID- 24026569
TI  - Vatairea macrocarpa lectin (VML) induces depressive-like behavior and expression
      of neuroinflammatory markers in mice.
AB  - Lectins are proteins capable of reversible binding to the carbohydrates in
      glycoconjugates that can regulate many physiological and pathological events.
      Galectin-1, a beta-galactoside-binding lectin, is expressed in the central
      nervous system (CNS) and exhibits neuroprotective functions. Additionally,
      lectins isolated from plants have demonstrated beneficial action in the CNS. One
      example is a lectin with mannose-glucose affinity purified from Canavalia
      brasiliensis seeds, ConBr, which displays neuroprotective and antidepressant
      activity. On the other hand, the effects of the galactose-binding lectin isolated
      from Vatairea macrocarpa seeds (VML) on the CNS are largely unknown. The aim of
      this study was to verify if VML is able to alter neural function by evaluating
      signaling enzymes, glial and inflammatory proteins in adult mice hippocampus, as
      well as behavioral parameters. VML administered by intracerebroventricular
      (i.c.v) route increased the immobility time in the forced swimming test (FST) 60
      min after its injection through a carbohydrate recognition domain-dependent
      mechanism. Furthermore, under the same conditions, VML caused an enhancement of
      COX-2, GFAP and S100B levels in mouse hippocampus. However, phosphorylation of
      Akt, GSK-3beta and mitogen-activated protein kinases named ERK1/2, JNK1/2/3 and
      p38(MAPK), was not changed by VML. The results reported here suggest that VML may
      trigger neuroinflammatory response in mouse hippocampus and exhibit a depressive
      like activity. Taken together, our findings indicate a dual role for galactose
      binding lectins in the modulation of CNS function.

PMID- 24026571
TI  - Long-term assessment of the environmental fate of heavy metals in agricultural
      soil after cessation of organic waste treatments.
AB  - The current study examined the anthropogenic accumulation and natural decrease in
      metal concentrations in agricultural soils following organic waste application.
      Three common organic wastes, including municipal sewage sludge, alcohol
      fermentation processing sludge, and pig manure compost (PMC), were applied
      annually to an agricultural soil under field conditions over 7 years (1994-2000)
      at a rate of 12.5, 25, and 50 ton ha(-1) year(-1) and the soil accumulation of
      three metals of concern (Cu, Pb, and Zn) was monitored. Subsequently, organic
      waste amendments ceased and the experimental plots were managed using
      conventional fertilization for another 10 years (2001-2010) and the natural
      decrease in metal concentrations monitored. Although Cu and Zn concentrations in
      all experimental plots did not exceed the relevant guideline values (150 mg kg(
      1) for Cu and 300 mg kg(-1) for Zn), significant increases in metal
      concentrations were observed from cumulative application of organic wastes over 7
      years. For instance, PMC treatment resulted in an increase in Cu and Zn from 9.8
      and 72 mg kg(-1) to 108.2 and 214.3 mg kg(-1), respectively. In addition, the
      natural decrease in Cu and Zn was not significant as soils amended with PMC
      showed only a 16 and 19 % decline in Cu and Zn concentrations, respectively, even
      10 years after amendment ceased. This research suggested that more attention must
      be paid during production of organic waste-based amendments and at the
      application stage.

PMID- 24026572
TI  - Haematological changes in fluorotic adults and children in fluoride endemic
      regions of Gaya district, Bihar, India.
AB  - Groundwater used for drinking and cooking was analysed for fluoride (F), and
      health surveys were conducted in Bodh Gaya, Amas and Bankebazaar blocks of the
      Gaya district, Bihar, India. Amas and Bankebazaar blocks were F endemic areas
      with mean F = 2.36 +/- 0.23 mg/L (N = 27). Bodh Gaya was considered as control
      area with mean F = 0.59 +/- 0.03 mg/L (N = 11). Health survey showed that more
      than 50 % of adults and more than 55 % of children had complaints of gastro
      intestinal (GI) disturbances in the F endemic areas, while less than 20 % of
      adults and less than 10 % of children complained of GI problems in the control
      areas. Haematological analyses were conducted on age- and sex-matched fluorotic
      subjects (N = 93) of F endemic areas, and non-fluorotic subjects (N = 52) of
      control area showed lowered haemoglobin, haematocrit, mean corpuscular volume,
      mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration in
      the fluorotic subjects, suggesting the occurrence of anaemia in the fluorotic
      subjects.

PMID- 24026574
TI  - Is gluten a cause of gastrointestinal symptoms in people without celiac disease?
AB  - The avoidance of wheat- and gluten-containing products is a worldwide phenomenon.
      While celiac disease is a well-established entity, the evidence base for gluten
      as a trigger of symptoms in patients without celiac disease (so-called 'non
      celiac gluten sensitivity' or NCGS) is limited. The problems lie in the
      complexity of wheat and the ability of its carbohydrate as well as protein
      components to trigger gastrointestinal symptoms, the potentially false assumption
      that response to a gluten-free diet equates to an effect of gluten withdrawal,
      and diagnostic criteria for coeliac disease. Recent randomized controlled re
      challenge trials have suggested that gluten may worsen gastrointestinal symptoms,
      but failed to confirm patients with self-perceived NCGS have specific gluten
      sensitivity. Furthermore, mechanisms by which gluten triggers symptoms have yet
      to be identified. This review discusses the most recent scientific evidence and
      our current understanding of NCGS. 

PMID- 24026573
TI  - Role of interleukin-13 in asthma.
AB  - Interleukin-13 is a pleiotropic TH2 cytokine that has been shown to be central to
      the pathogenesis of asthma. Some of the most prominent of the effects of IL-13
      include increases in goblet cell differentiation, activation of fibroblasts,
      elevation of bronchial hyperresponsiveness, and switching of B cell antibody
      production from IgM to IgE. The relevances of these effects to asthma have been
      carefully studied in both animal models and more recently in human studies. As
      the role of IL-13 in asthma has become more defined, a number of potential
      biomarkers for TH2 airway inflammation, and hence IL-13 activity, have been
      identified, including blood and sputum eosinophils, total serum IgE, proteins
      derived from the bronchial epithelium (e.g., serum periostin), and exhaled nitric
      oxide. Most importantly, many of these markers for TH2 inflammation are strong
      predictors for positive responses to inhaled corticosteroid treatment. These
      biomarkers may also be useful in identifying patients who are most likely to
      benefit from specific IL-13 antagonism, as was demonstrated in a recent clinical
      trial of anti-IL-13 antibody therapy (lebrikizumab) in patients with poorly
      controlled asthma despite using inhaled corticosteroids. In that study,
      significant improvements in FEV1 were observed in patients with elevations of
      serum periostin but not in patients with normal periostin levels. These data
      indicate that IL-13 antagonists may fulfill an important unmet need in patients
      with poorly controlled asthma and biologic evidence of persistent IL-13 activity.

PMID- 24026575
TI  - DFT and docking studies of rhodostreptomycins A and B and their interactions with
      solvated/nonsolvated Mg2+ and Ca2+ ions.
AB  - The interactions of L-aminoglucosidic stereoisomers such as rhodostreptomycins A
      (Rho A) and B (Rho B) with cations (Mg(2+), Ca(2+), and H(+)) were studied by a
      quantum mechanical method that utilized DFT with B3LYP/6-311G. Docking studies
      were also carried out in order to explore the surface recognition properties of L
      aminoglucoside with respect to Mg(2+) and Ca(2+) ions under solvated and
      nonsolvated conditions. Although both of the stereoisomers possess similar
      physicochemical/antibiotic properties against Helicobacter pylori, the
      thermochemical values for these complexes showed that its high affinity for
      Mg(2+) cations caused the hydration of Rho B. According to the results of the
      calculations, for Rho A-Ca(2+)(H2O)6, DeltaH = -72.21 kcal mol(-1); for Rho B
      Ca(2+)(H2O)6, DeltaH = -72.53 kcal mol(-1); for Rho A-Mg(2+)(H2O)6, DeltaH = 
      72.99 kcal mol(-1) and for Rho B-Mg(2+)(H2O)6, DeltaH = -95.00 kcal mol(-1),
      confirming that Rho B binds most strongly with hydrated Mg(2+), considering the
      energy associated with this binding process. This result suggests that Rho B
      forms a more stable complex than its isomer does with magnesium ion. Docking
      results show that both of these rhodostreptomycin molecules bind to solvated
      Ca(2+) or Mg(2+) through hydrogen bonding. Finally, Rho B is more stable than Rho
      A when protonation occurs.

PMID- 24026578
TI  - Conformational analysis and intramolecular hydrogen bonding of cis-3-aminoindan-1
      ol: a quantum chemical study.
AB  - In the present work, we carried out a conformational analysis of cis-3-aminoindan
      1-ol and evaluated the role of the intramolecular hydrogen bond in the
      stabilization of various conformers using quantum mechanical DFT (B3LYP) and MP2
      methods. On the basis of relative energies, we have found nine conformational
      minima, which can interchange through the ring-puckering and the internal
      rotation of the OH and NH2 groups on the five-membered ring. The intramolecular
      hydrogen bonds such as OH????pi, NH????pi, NH????OH and HN????HO are expected to
      be of critical importance for the conformational stabilities. The intramolecular
      interactions of the minima have been analyzed by calculation of electron density
      (rho) and Laplacian (rho) at the bond critical points (BCPs) using atoms-in
      molecule (AIM) theory. The existence or absence of OH????pi and NH????pi in cis-3
      aminoindan-1-ol remains unclear since the geometrical investigation has not been
      confirmed by topological criteria. The results of theoretical calculations
      demonstrate that this compound exists predominantly in one ring-puckering form
      stabilized by strong hydrogen bond HN????HO Interaction.

PMID- 24026579
TI  - Overt irritability/anger in unipolar major depressive episodes: past and current
      characteristics and implications for long-term course.
AB  - IMPORTANCE: Although symptoms of irritability or anger are not central to the
      diagnosis of unipolar major depressive episodes (MDEs), these symptoms have been
      found, in cross-sectional studies, to be highly prevalent and associated with
      increased comorbidity and depressive illness burden. OBJECTIVE: To determine the
      prevalence of overtly expressed irritability/anger and its effect on intake
      presentation and the long-term course of illness. DESIGN: A prospective,
      naturalistic investigation of patients with unipolar MDEs, studied systematically
      at intake and during up to 31 years of follow-up. SETTING: Five US academic
      medical centers. PARTICIPANTS: Patients entered the National Institute of Mental
      Health Collaborative Depression Study during an MDE in 1978, 1979, 1980, or 1981.
      Patients with unipolar MDE at intake (n = 536) were divided into those with and
      those without current comorbid overtly expressed irritability/anger. EXPOSURE: In
      this observational, longitudinal study, patients received treatment that was
      recorded but not controlled. MAIN OUTCOMES AND MEASURES: Groups were compared on
      illness severity and chronicity, psychosocial impairment, quality of life,
      suicidal behavior, lifetime comorbid diagnoses, impulse control, and measures
      associated with bipolarity. RESULTS: Overt irritability/anger was present in 292
      of 536 participants with a unipolar MDE at study intake (54.5%). It was
      associated with significantly increased depressive severity, longer duration of
      the index MDE, poorer impulse control, a more chronic and severe long-term course
      of illness, higher rates of lifetime comorbid substance abuse and anxiety
      disorder, more antisocial personality disorders, greater psychosocial impairment
      before intake and during follow-up, reduced life satisfaction, and a higher rate
      of bipolar II disorder in relatives. No association was found with increased
      suicidal ideation or behavior. Results were not explained by comorbidity or other
      manic spectrum symptoms. CONCLUSIONS AND RELEVANCE: This study extends results of
      cross-sectional investigations and indicates that irritability/anger during MDEs
      is a highly prevalent clinical marker of a more severe, chronic, and complex
      depressive illness. Findings have important implications for assessment and
      treatment.

PMID- 24026580
TI  - Managing maternal cardiac arrest in Canada:--we're doing OK, but we can do
      better.

PMID- 24026583
TI  - Gooseberries on a table: Adriaen Coorte.

PMID- 24026584
TI  - Mediterranean diet may reduce stroke risk in individuals with genetic
      predisposition to diabetes.

PMID- 24026585
TI  - FDA warning and study highlight fluoroquinolone risks.

PMID- 24026595
TI  - A piece of my mind. Syntax of survival.

PMID- 24026596
TI  - Treatment of severe alcoholic hepatitis with corticosteroids and pentoxifylline.

PMID- 24026597
TI  - Financial incentives in primary care practice: the struggle to achieve population
      health goals.

PMID- 24026598
TI  - Prednisolone with vs without pentoxifylline and survival of patients with severe
      alcoholic hepatitis: a randomized clinical trial.
AB  - IMPORTANCE: Prednisolone or pentoxifylline is recommended for severe alcoholic
      hepatitis, a life-threatening disease. The benefit of their combination is
      unknown. OBJECTIVE: To determine whether the addition of pentoxifylline to
      prednisolone is more effective than prednisolone alone. DESIGN, SETTING, AND
      PARTICIPANTS: Multicenter, randomized, double-blind clinical trial conducted
      between December 2007 and March 2010 in 1 Belgian and 23 French hospitals of 270
      patients aged 18 to 70 years who were heavy drinkers with severe biopsy-proven
      alcoholic hepatitis, as indicated by recent onset of jaundice in the prior 3
      months and a Maddrey score of at least 32. Duration of follow-up was 6 months.
      The last included patient completed the study in October 2010. None of the
      patients were lost to follow-up for the main outcome. INTERVENTION: Patients were
      randomly assigned to receive either a combination of 40 mg of prednisolone once a
      day and 400 mg of pentoxifylline 3 times a day (n=133) for 28 days, or 40 mg of
      prednisolone and matching placebo (n=137) for 28 days. MAIN OUTCOMES AND
      MEASURES: Six-month survival, with secondary end points of development of
      hepatorenal syndrome and response to therapy based on the Lille model, which
      defines treatment nonresponders after 7 days of initiation of treatment. RESULTS:
      In intention-to-treat analysis, 6-month survival was not different in the
      pentoxifylline-prednisolone and placebo-prednisolone groups (69.9% [95% CI, 62.1%
      77.7%] vs 69.2% [95% CI; 61.4%-76.9%], P = .91), corresponding to 40 vs 42
      deaths, respectively. In multivariable analysis, only the Lille model and the
      Model for End-Stage Liver Disease score were independently associated with 6
      month survival. At 7 days, response to therapy assessed by the Lille model was
      not significantly different between the 2 groups (Lille model score, 0.41 [95%
      CI, 0.36-0.46] vs 0.40 [95% CI, 0.35-0.45], P = .80). The probability of being a
      responder was not different in both groups (62.6% [95% CI, 53.9%-71.3%] vs 61.9%
      [95% CI, 53.7%-70.3%], P = .91). The cumulative incidence of hepatorenal syndrome
      at 6 months was not significantly different in the pentoxifylline-prednisolone
      and the placebo-prednisolone groups (8.4% [95% CI, 4.8%-14.8%] vs 15.3% [95% CI,
      10.3%-22.7%], P = .07). CONCLUSION AND RELEVANCE: In patients with alcoholic
      hepatitis, 4-week treatment with pentoxifylline and prednisolone, compared with
      prednisolone alone, did not result in improved 6-month survival. The study may
      have been underpowered to detect a significant difference in incidence of
      hepatorenal syndrome, which was less frequent in the group receiving
      pentoxifylline. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01214226.

PMID- 24026599
TI  - Effects of individual physician-level and practice-level financial incentives on
      hypertension care: a randomized trial.
AB  - IMPORTANCE: Pay for performance is intended to align incentives to promote high
      quality care, but results have been contradictory. OBJECTIVE: To test the effect
      of explicit financial incentives to reward guideline-recommended hypertension
      care. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized trial of 12 Veterans
      Affairs outpatient clinics with 5 performance periods and a 12-month washout that
      enrolled 83 primary care physicians and 42 nonphysician personnel (eg, nurses,
      pharmacists). INTERVENTIONS: Physician-level (individual) incentives, practice
      level incentives, both, or none. Intervention participants received up to 5
      payments every 4 months; all participants could access feedback reports. MAIN
      OUTCOMES AND MEASURES: Among a random sample, number of patients achieving
      guideline-recommended blood pressure thresholds or receiving an appropriate
      response to uncontrolled blood pressure, number of patients prescribed guideline
      recommended medications, and number who developed hypotension. RESULTS: Mean (SD)
      total payments over the study were $4270 ($459), $2672 ($153), and $1648 ($248)
      for the combined, individual, and practice-level interventions, respectively. The
      unadjusted baseline and final percentages and the adjusted absolute change over
      the study in patients meeting the combined blood pressure/appropriate response
      measure were 75% to 84% and 8.84% (95% CI, 4.20% to 11.80%) for the individual
      group, 80% to 85% and 3.70% (95% CI, 0.24% to 7.68%) for the practice-level
      group, 79% to 88% and 5.54% (95% CI, 1.92% to 9.52%) for the combined group, and
      86% to 86% and 0.47% (95% CI, -3.12% to 4.04%) for the control group. The
      adjusted absolute estimated difference in the change between the proportion of
      patients with blood pressure control/appropriate response for individual
      incentive and control groups was 8.36% (95% CI, 2.40% to 13.00%; P=.005). The
      other incentive groups did not show a significant change compared with controls
      for this outcome. For medications, the unadjusted baseline and final percentages
      and the adjusted absolute change were 61% to 73% and 9.07% (95% CI, 4.52% to
      13.44%), 56% to 65% and 4.98% (95% CI, 0.64% to 10.08%), 65% to 80% and 7.26%
      (95% CI, 2.92% to 12.48%), and 63% to 72% and 4.35% (95% CI, -0.28% to 9.28%),
      respectively. These changes in the use of guideline-recommended medications were
      not significant in any of the incentive groups compared with controls, nor was
      the incidence of hypotension. The effect of the incentive was not sustained after
      a washout. CONCLUSIONS AND RELEVANCE: Individual financial incentives, but not
      practice-level or combined incentives, resulted in greater blood pressure control
      or appropriate response to uncontrolled blood pressure; none of the incentives
      resulted in greater use of guideline-recommended medications or increased
      incidence of hypotension compared with controls. Further research is needed on
      the factors that contributed to these findings. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00302718.

PMID- 24026602
TI  - Selective serotonin reuptake inhibitors for stroke recovery.
AB  - CLINICAL QUESTION: Are selective serotonin reuptake inhibitors (SSRIs) associated
      with better recovery after stroke? BOTTOM LINE: SSRIs may be associated with
      improved recovery after stroke, even in persons without depression. However, much
      of the evidence is of poor quality. Large, high-quality trials are needed to
      evaluate the validity of the current evidence and improve precision of estimates
      of any treatment benefits.

PMID- 24026601
TI  - Implementation of an outpatient electronic health record and emergency department
      visits, hospitalizations, and office visits among patients with diabetes.
AB  - IMPORTANCE: The US federal government is spending billions of dollars in
      physician incentives to encourage the meaningful use of electronic health records
      (EHRs). Although the use of EHRs has potential to improve patient health
      outcomes, the existing evidence has been limited and inconsistent. OBJECTIVE: To
      examine the association between implementing a commercially available outpatient
      EHR and emergency department (ED) visits, hospitalizations, and office visits for
      patients with diabetes mellitus. DESIGN, SETTING, AND POPULATION: Staggered EHR
      implementation across outpatient clinics in an integrated delivery system (Kaiser
      Permanente Northern California) between 2005 and 2008 created an opportunity for
      studying changes associated with EHR use. Among a population-based sample of
      169,711 patients with diabetes between 2004 and 2009, we analyzed 4,997,585
      person-months before EHR implementation and 4,648,572 person-months after an EHR
      was being used by patients' physicians. MAIN OUTCOMES AND MEASURES: We examined
      the association between EHR use and unfavorable clinical events (ED visits and
      hospitalizations) and office visit use among patients with diabetes, using
      multivariable regression with patient-level fixed-effect analyses and adjustment
      for trends over time. RESULTS: In multivariable analyses, use of the EHR was
      associated with a statistically significantly decreased number of ED visits,
      28.80 fewer visits per 1000 patients annually (95% CI, 20.28 to 37.32), from a
      mean of 519.12 visits per 1000 patients annually without using the EHR to 490.32
      per 1000 patients when using the EHR. The EHR was also associated with 13.10
      fewer hospitalizations per 1000 patients annually (95% CI, 7.37 to 18.82), from a
      mean of 251.60 hospitalizations per 1000 patients annually with no EHR to 238.50
      per 1000 patients annually when using the EHR. There were similar statistically
      significant reductions in nonelective hospitalizations (10.92 fewer per 1000
      patients annually) and hospitalizations for ambulatory care-sensitive conditions
      (7.08 fewer per 1000 patients annually). There was no statistically significant
      association between EHR use and office visit rates. CONCLUSIONS AND RELEVANCE:
      Among patients with diabetes, use of an outpatient EHR in an integrated delivery
      system was associated with modest reductions in ED visits and hospitalizations
      but not office visit rates. Further studies are needed to quantify the
      association of EHR use with changes in costs.

PMID- 24026600
TI  - Effect of pay-for-performance incentives on quality of care in small practices
      with electronic health records: a randomized trial.
AB  - IMPORTANCE: Most evaluations of pay-for-performance (P4P) incentives have focused
      on large-group practices. Thus, the effect of P4P in small practices, where many
      US residents receive care, is largely unknown. Furthermore, whether electronic
      health records (EHRs) with chronic disease management capabilities support small
      practice response to P4P has not been studied. OBJECTIVE: To assess the effect of
      P4P incentives on quality in EHR-enabled small practices in the context of an
      established quality improvement initiative. DESIGN, SETTING, AND PARTICIPANTS: A
      cluster-randomized trial of small (<10 clinicians) primary care clinics in New
      York City from April 2009 through March 2010. A city program provided all
      participating clinics with the same EHR software with decision support and
      patient registry functionalities and quality improvement specialists offering
      technical assistance. INTERVENTIONS: Incentivized clinics were paid for each
      patient whose care met the performance criteria, but they received higher
      payments for patients with comorbidities, who had Medicaid insurance, or who were
      uninsured (maximum payments: $200/patient; $100,000/clinic). Quality reports were
      given quarterly to both the intervention and control groups. MAIN OUTCOMES AND
      MEASURES: Comparison of differences in performance improvement, from the
      beginning to the end of the study, between control and intervention clinics for
      aspirin or antithrombotic prescription, blood pressure control, cholesterol
      control, and smoking cessation interventions. Mixed-effects logistic regression
      was used to account for clustering of patients within clinics, with a treatment
      by time interaction term assessing the statistical significance of the effect of
      the intervention. RESULTS: Participating clinics (n = 42 for each group) had
      similar baseline characteristics, with a mean of 4592 (median, 2500) patients at
      the intervention group clinics and 3042 (median, 2000) at the control group
      clinics. Intervention clinics had greater adjusted absolute improvement in rates
      of appropriate antithrombotic prescription (12.0% vs 6.1%, difference: 6.0% [95%
      CI, 2.2% to 9.7%], P = .001 for interaction term), blood pressure control (no
      comorbidities: 9.7% vs 4.3%, difference: 5.5% [95% CI, 1.6% to 9.3%], P = .01 for
      interaction term; with diabetes mellitus: 9.0% vs 1.2%, difference: 7.8% [95% CI,
      3.2% to 12.4%], P = .007 for interaction term; with diabetes mellitus or ischemic
      vascular disease: 9.5% vs 1.7%, difference: 7.8% [95% CI, 3.0% to 12.6%], P = .01
      for interaction term), and in smoking cessation interventions (12.4% vs 7.7%,
      difference: 4.7% [95% CI, -0.3% to 9.6%], P = .02 for interaction term).
      Intervention clinics performed better on all measures for Medicaid and uninsured
      patients except cholesterol control, but no differences were statistically
      significant. CONCLUSIONS AND RELEVANCE: Among small EHR-enabled clinics, a P4P
      incentive program compared with usual care resulted in modest improvements in
      cardiovascular care processes and outcomes. Because most proposed P4P programs
      are intended to remain in place more than a year, further research is needed to
      determine whether this effect increases or decreases over time. TRIAL
      REGISTRATION: clinicaltrials.gov Identifier: NCT00884013.

PMID- 24026603
TI  - Scalp pustules in a patient receiving chemotherapy.

PMID- 24026604
TI  - Use of electronic health records for automated screening of growth disorders in
      primary care.

PMID- 24026605
TI  - Surgery for pelvic organ prolapse.

PMID- 24026606
TI  - Surgery for pelvic organ prolapse--reply.

PMID- 24026607
TI  - Diagnosis of primary open-angle glaucoma.

PMID- 24026608
TI  - Diagnosis of primary open-angle glaucoma--reply.

PMID- 24026609
TI  - Tumor necrosis factor inhibitors and myocardial infarction in psoriasis.

PMID- 24026612
TI  - Tumor necrosis factor inhibitors and myocardial infarction in psoriasis--reply.

PMID- 24026614
TI  - Proprietary prescribing in Great Britain.

PMID- 24026615
TI  - JAMA patient page. Robotic surgery.

PMID- 24026616
TI  - Gene silencing of claudin-6 enhances cell proliferation and migration accompanied
      with increased MMP-2 activity via p38 MAPK signaling pathway in human breast
      epithelium cell line HBL-100.
AB  - Disruption or loss of tight junction structure and function is associated with
      tumor growth, invasion and metastasis in tumors of human epithelial origin. Since
      claudin is the most important backbone protein of tight junctions, the
      downregulation or loss of claudin expression is hypothesized to be important for
      tumor development and metastasis. In the current study, RNA interference (RNAi)
      was used to knock down the expression of claudin-6 to investigate the effect of
      claudin-6 downregulation on the malignant phenotype in the human breast
      epithelium cell line HBL-100. The junctional function was investigated by
      measuring the transepithelial electrical resistance across the confluent
      epithelial cell layer. Manual cell counting and wound healing assays were
      performed to examine cell proliferation and migration. Changes in matrix
      metalloproteinase-2 (MMP-2) expression and activity were examined by reverse
      transcription polymerase chain reaction (RT-PCR) and gelatin zymography. The
      expression of p38 mitogen-activated protein kinases (MAPKs) and phosphorylated
      p38 MAPK were measured by western blot analysis. Claudin-6 knockdown resulted in
      significantly lower transepithelial electrical resistance (P<0.001), higher
      growth rate (P<0.001) and migratory ability (P<0.001) accompanied with an
      increased MMP-2 expression and activity (P<0.001). Furthermore, a decreased
      expression of phosphorylated p38 MAPK (P<0.001) was detected in HBL-100 cells.
      These observations support the hypothesis that a decreased expression of claudin
      6 contributes to the malignant progression of human breast cancer.

PMID- 24026617
TI  - Structures and anti-cancer properties of two binuclear copper complexes.
AB  - The crystals of two binuclear copper-based complexes were obtained. One complex
      can remarkably induce apoptosis and inhibit angiogenesis to mediate tumour growth
      at a greater extent. Furthermore, this complex showed a strong energy-dependent
      and non-endocytotic uptake and exhibited multiple anti-cancer functions by
      inhibiting the expressions of p-Akt and p-Erk1/2 proteins and by decreasing the
      levels of reactive oxygen species. 

PMID- 24026618
TI  - Association of endothelin-converting enzyme-1b C-338A polymorphism with increased
      risk of ischemic stroke in Chinese Han population.
AB  - Endothelin-converting enzyme-1b (ECE-1b) C-338A is a polymorphism located in ECE
      1 gene promoter, which has been reported to correlate with the risk of carotid
      atherosclerosis. We conducted a hospital-based case-control study of 309 patients
      with ischemic stroke and 309 controls matched on age and gender. The frequencies
      of ECE-1b-338 CC, CA, and AA genotypes in cases (45.0, 40.4, and 14.6 %) were
      significantly different from those of controls (53.1, 39.1, and 7.8 %, chi(2) =
      8.519, P = 0.014), respectively. Compared with C carriers, A alleles showed
      correlation with a 42 % increased risk of ischemic stroke (adjusted odds ratio
      (OR) = 1.42, 95 % CI = 1.11-1.81). After adjustment for potential risk factors,
      the AA genotype still kept positive correlation with ischemic stroke (OR = 1.78;
      95 % CI = 1.06-3.54). In stratified analyses, the significant association of the
      A allele with ischemic stroke was observed in female subjects (adjusted OR =
      1.64, 95 % CI = 1.17-2.89) and the subjects with age >= 64 years old (adjusted OR
      = 2.09, 95 % CI = 1.38-3.23). The present study suggested that the C-338A
      polymorphism of the ECE-1b gene was associated with an increased risk of ischemic
      stroke in the Chinese Han population.

PMID- 24026619
TI  - Anti-inflammatory effect of acetylpuerarin on eicosanoid signaling pathway in
      primary rat astrocytes.
AB  - Astrocytes activation has been implicated in the inflammatory responses
      underlying brain injury and neurodegenerative diseases including bacterial
      infections, cerebral ischemia, and Parkinson's diseases. Acetylpuerarin is a
      newly modified isoflavone based on puerarin that has neuroprotective and
      antioxidant effects. In this study, we investigated the anti-inflammatory action
      of acetylpuerarin in regulating the eicosanoids generation and its underlying
      molecular mechanisms in lipopolysaccharide (LPS)-induced production of
      arachidonic acid (AA) metabolites in primary rat astrocytes. The results showed
      that acetylpuerarin concentration dependently inhibited the LPS-induced
      production of AA metabolites such as prostaglandin E2 (PGE2) and leukotriene C4
      (LTC4), and acetylpuerarin significantly attenuated the expression and
      immunoreactivity of group V secretory phospholipase A2 (sPLA2) protein induced by
      LPS in astrocytes. Furthermore, in astrocytes pretreated with acetylpuerarin, the
      time course of phosphorylation of extracellular signal-regulated kinase (ERK)1/2
      and of cytosolic PLA2 alpha (cPLA2alpha) and expression of transcription factors,
      nuclear factor kappa B (NF-kappaB), was markedly truncated. Acetylpuerarin
      concentration dependently abolished the LPS-induced expressions of AA
      metabolizing enzymes including cyclooxygenase-2 (COX-2) and lipooxygenase-5 (LOX
      5). This study indicates that acetylpuerarin inhibited LPS-induced AA
      metabolizing enzymes and AA metabolites in astrocytes via downregulation
      expression of group V sPLA2 and phosphorylation of ERK1/2, cPLA2alpha, and NF
      kappaB. These findings reveal, in part, the molecular basis underlying the anti
      inflammatory properties of acetylpuerarin. 

PMID- 24026620
TI  - Evaluation of Crohn's disease activity: initial validation of a magnetic
      resonance enterography global score (MEGS) against faecal calprotectin.
AB  - OBJECTIVES: To develop an MRI enterography global score (MEGS) of Crohn's disease
      (CD) activity compared with a reference standard of faecal calprotectin (fC), C
      reactive protein (CRP) and Harvey-Bradshaw index (HBI). METHODS: Calprotectin,
      CRP and HBI were prospectively recorded for 71 patients (median age 33, male 35)
      with known/suspected CD undergoing MRI enterography. Two observers in consensus
      scored activity for nine bowel segments, grading mural thickness, T2 signal,
      mesenteric oedema, T1 enhancement and pattern, and haustral loss. Segmental
      scores were multiplied according to disease length. Five points each were added
      for lymphadenopathy, comb sign, fistulae and abscesses to derive the MEGS. A
      previously validated MRI CD activity score (CDAS) was also calculated. MRI scores
      were correlated with clinical references using Spearman's rank. A logistic
      regression diagnostic model was built to discriminate active (fC > 100 MUg/g)
      from inactive disease. RESULTS: MEGS and CDAS were significantly correlated with
      fC (r = 0.46, P < 0.001) and (r = 0.39, P = 0.001) respectively. MEGS correlated
      with CRP (r = 0.39, P = 0.002). The model for discriminating active from inactive
      disease achieved an area under the receiver-operating curve of 0.75 and 0.66
      after leave-one-out analysis. CONCLUSION: A magnetic resonance enterography
      global score (MEGS) of CD activity correlated significantly with fC levels. KEY
      POINTS: * Magnetic resonance imaging is now widely used to assess Crohn's
      disease. * Existing MRI activity scores depend on local segmental
      endoscopic/histological reference standards. * Scores including assessment of
      disease extent/complications better demonstrate full disease burden. * This new
      global Crohn's disease burden score correlates with calprotectin and CRP. * The
      MRI enterography score of disease activity can complement existing clinical
      markers.

PMID- 24026621
TI  - Diagnostic confidence analysis in the magnetic resonance imaging of ovarian and
      deep endometriosis: comparison with surgical results.
AB  - OBJECTIVE: To assess the diagnostic confidence of multiple readers in the
      magnetic resonance imaging (MRI) diagnosis of endometriosis. METHODS: Sixty-five
      patients (mean age 33; range 19-45 years) who had undergone MRI were
      retrospectively evaluated. Five regions were analysed and the presence of
      endometriosis was scored on a five-point scale in order to assess the diagnostic
      confidence. Statistical analysis included receiver operating characteristic (ROC)
      curve analysis, the Cohen weighted test and sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV), accuracy, positive
      likelihood ratio (LR+) and negative likelihood ratio (LR-). RESULTS: The areas
      under the curve (AUC) in the detection of ovarian endometrioma were 0.942, 0.893
      and 0.883 for readers 1, 2 and 3, respectively; in the uterosacral ligament (USL)
      AUCs were 0.907, 0.804 and 0.842; in the vaginal fornix (VF) 0.819, 0.733 and
      0.69; in the anterior compartment 0.916, 0.833 and 0.873; and in the
      rectum/sigma/pouch of Douglas (RSD) 0.936, 0.856 and 0.834. CONCLUSIONS:
      Diagnostic confidence of the observers is different according to the region of
      the nodules of endometriosis and it can be challenging in the VF and for the less
      experience readers also in the AC and RSD. Moreover the degree of uncertain
      diagnosis for the less expert readers may reach up to one third of the
      examinations. KEY POINTS: * Magnetic resonance imaging (MRI) is increasingly used
      to assess endometriosis * The diagnostic confidence of observers varies according
      to the location of endometriosis * The diagnosis is more difficult to establish
      by MRI in some anatomical locations * Specific training should be given
      concerning those locations that cause difficulty.

PMID- 24026622
TI  - Lindon Eaves: the astonishing decade.
AB  - The contributions of Lindon Eaves to the development of the subject of behavior
      genetics are reviewed, with a focus on the 1970s, the first astonishing decade of
      his career when he made major theoretical advances in the design and power of
      human quantitative genetic studies, including treatment of assortative mating,
      cultural transmission, sex limitation, sibling effects, gene-environment
      interaction and covariation, and multivariate genetic analysis. He also made
      important substantive contributions to our understanding of the causes of
      individual differences in cognition, personality, social and sexual attitudes,
      and smoking. 

PMID- 24026623
TI  - Assessment of vandetanib as an inhibitor of various human renal transporters:
      inhibition of multidrug and toxin extrusion as a possible mechanism leading to
      decreased cisplatin and creatinine clearance.
AB  - Vandetanib was evaluated as an inhibitor of human organic anion transporter 1
      (OAT1), OAT3, organic cation transporter 2 (OCT2), and multidrug and toxin
      extrusion (MATE1 and MATE2K) transfected (individually) into human embryonic
      kidney 293 cells (HEK293). Although no inhibition of OAT1 and OAT3 was observed,
      inhibition of OCT2-mediated uptake of 1-methyl-4-phenylpyridinium (MPP(+)) and
      metformin was evident (IC(50) of 73.4 +/- 14.8 and 8.8 +/- 1.9 uM, respectively).
      However, vandetanib was an even more potent inhibitor of MATE1- and MATE2K
      mediated uptake of MPP(+) (IC(50) of 1.23 +/- 0.05 and 1.26 +/- 0.06 uM,
      respectively) and metformin (IC(50) of 0.16 +/- 0.05 and 0.30 +/- 0.09 uM,
      respectively). Subsequent cytotoxicity studies demonstrated that transport
      inhibition by vandetanib (2.5 uM) significantly decreased the sensitivity [right
      shift in concentration of cisplatin giving rise to 50% cell death; IC(50(CN))] of
      MATE1-HEK and MATE2K-HEK cells to cisplatin [IC(50(CN)) of 1.12 +/- 0.13 versus
      2.39 +/- 0.44 uM; 0.85 +/- 0.09 versus 1.99 +/- 0.16 uM; P < 0.05), but not OCT2
      HEK cells (1.36 +/- 0.19 versus 1.47 +/- 0.24 uM) versus vandetanib untreated
      cells and Mock-HEK cells [IC(50(CN)) of 2.34 +/- 0.31 uM]. In summary, the
      results show that vandetanib is a potent inhibitor of MATE1 and MATE2K (versus
      OCT2). Inhibition of the two transporters may explain why there are reports of
      decreased creatinine clearance, and increased cisplatin nephrotoxicity (reduced
      cisplatin clearance), in some subjects receiving vandetanib therapy.

PMID- 24026624
TI  - Can we still dream when the mind is blank? Sleep and dream mentations in auto
      activation deficit.
AB  - Bilateral damage to the basal ganglia causes auto-activation deficit, a
      neuropsychological syndrome characterized by striking apathy, with a loss of self
      driven behaviour that is partially reversible with external stimulation. Some
      patients with auto-activation deficit also experience a mental emptiness, which
      is defined as an absence of any self-reported thoughts. We asked whether this
      deficit in spontaneous activation of mental processing may be reversed during REM
      sleep, when dreaming activity is potentially elicited by bottom-up brainstem
      stimulation on the cortex. Sleep and video monitoring over two nights and
      cognitive tests were performed on 13 patients with auto-activation deficit
      secondary to bilateral striato-pallidal lesions and 13 healthy subjects. Dream
      mentations were collected from home diaries and after forced awakenings in non
      REM and REM sleep. The home diaries were blindly analysed for length, complexity
      and bizarreness. A mental blank during wakefulness was complete in six patients
      and partial in one patient. Four (31%) patients with auto-activation deficit
      (versus 92% of control subjects) reported mentations when awakened from REM
      sleep, even when they demonstrated a mental blank during the daytime (n = 2).
      However, the patients' dream reports were infrequent, short, devoid of any
      bizarre or emotional elements and tended to be less complex than the dream
      mentations of control subjects. The sleep duration, continuity and stages were
      similar between the groups, except for a striking absence of sleep spindles in 6
      of 13 patients with auto-activation deficit, despite an intact thalamus. The
      presence of spontaneous dreams in REM sleep in the absence of thoughts during
      wakefulness in patients with auto-activation deficit supports the idea that
      simple dream imagery is generated by brainstem stimulation and is sent to the
      sensory cortex. However, the lack of complexity in these dream mentations
      suggests that the full dreaming process (scenario, emotions, etc.) require these
      sensations to be interpreted by higher-order cortical areas. The absence of sleep
      spindles in localized lesions in the basal ganglia highlights the role of the
      pallidum and striatum in spindling activity during non-REM sleep. 

PMID- 24026625
TI  - Bisphosphonate long-term treatment related bilateral subtrochanteric femoral
      fracture. Can teriparatide be useful?
AB  - Long-term treatment with bisphosphonates has been related to atypical femoral
      fractures. We report the clinical case of a woman who suffered a proximal
      diaphyseal oblique fracture of the left femur after uninterrupted 13-year
      treatment with alendronate. Shortly after surgery, a painful lytic image in the
      external cortex of her right femur diaphysis was detected. Some papers have
      suggested surgical treatment to repair femur fractures after long-term treatment
      with bisphosphonates. Otherwise, two studies have shown healing acceleration of
      bone fractures with teriparatide. A lytic lesion was treated with teriparatide
      obtaining progressive disappearance of symptoms as well as bone healing. This
      outcome may suggest a way of prevention of complete fractures in symptomatic
      patients with long-term treatment with bisphosphonates.

PMID- 24026626
TI  - Safety of endoscopic ultrasonography in elderly patients: a single center
      prospective trial.
AB  - BACKGROUND AND AIMS: The aim of this prospective study is to evaluate the safety
      of both diagnostic and therapeutic endosonography (EUS) in geriatric population.
      METHODS: The study population, consisting of 222 patients who underwent
      endosonographic evaluation for different indications, was divided into two
      groups. Group I consisted of 165 patients, >= 65 years old; Group II consisted of
      57 controls, <65 years old. The demographic information with clinical parameters,
      procedure medication used and complications was noted. RESULTS: The median age of
      Group I was 72 years (range 65-93 years) vs. 46 years (range 26-64 years) for
      Group II. Female-to-male ratio was 82/83 in Group I, while 32/25 in Group II.
      Pulse rate (84 vs. 89 beats/min, p = 0.024) and basal oxygen saturation (94 vs.
      97 %, p < 0.001) levels were lower in Group I when compared with the control
      group, while systolic blood pressure measurements (150 vs. 130 mmHg, p < 0.001)
      were significantly higher in Group I. No cases of procedure-related bleeding,
      perforation and mortality were observed in both groups. CONCLUSION: Despite the
      well-known relative increased procedural risks, advanced age is not a
      contraindication for advanced endoscopic interventions. EUS can be regarded as a
      safe and effective procedure in >= 65 years old population.

PMID- 24026627
TI  - Prostanoid therapy for pulmonary arterial hypertension: a meta-analysis of
      survival outcomes.
AB  - BACKGROUND: Prostanoids have played an important role in the treatment of
      pulmonary arterial hypertension (PAH). However, whether prostanoid therapy
      provides a survival advantage is still not clear. The aim of this meta-analysis
      was to evaluate the efficacy and safety of prostanoids in PAH, focusing on the
      improvement in overall survival. METHODS: Trials were identified from the
      Cochrane Library, EMBASE, and PUBMED databases. We calculated risk ratios (RR)
      for dichotomous data and weighted mean differences with 95 % confidence intervals
      (CI) for continuous data. RESULTS: Fourteen trials with a total of 2,244 adult
      patients (1,189 patients in the prostanoid treatment group and 1,055 patients in
      the placebo group) were included in the meta-analysis. All-cause mortality rate
      in the control group was 4.17 %. In a 13.4-week follow-up, prostanoid treatment
      was associated with a 44 % reduction in mortality (RR 0.56; 95 % CI 0.35-0.88; P
      = 0.01).Subgroup analysis suggested that only treatment with intravenous
      prostanoids provided a survival benefit. Compared with placebo, prostanoids
      significantly reduced clinical worsening (RR 0.60; 95 % CI 0.46-0.80; P =
      0.0003), increased the 6-min walk distance by 27.95 m, reduced mean pulmonary
      arterial pressure and pulmonary vascular resistance, and increased the cardiac
      index and mixed venous oxygen saturation. However, patients receiving prostanoid
      treatment showed a much higher incidence (RR 3.25; 95 % CI 2.07-5.10; P<0.00001)
      of withdrawal due to its adverse effects. CONCLUSION: The results of this meta
      analysis suggest that treatment with prostanoids improves the survival of
      patients with PAH.

PMID- 24026628
TI  - Patient-important activity and participation outcomes in clinical trials
      involving children with chronic conditions.
AB  - PURPOSE: Children with chronic conditions experience medical issues over long
      term periods of time which can have lasting emotional and social consequences
      impacting daily life and functioning. Activities and participation outcomes are
      needed in order to comprehensively assess child-important health in clinical
      trials. Our objective was to review the extent to which activity and
      participation outcomes are included in clinical trials of childhood chronic
      disease and to determine what trial characteristics are associated with their
      use. METHODS: A review of a large clinical trial registration database
      (clinicaltrials.gov) was conducted over the 2010 calendar year. The measures used
      to assess primary and secondary endpoints were coded according to the ICF
      classification system. Trial characteristics that might be associated with
      activity and participation outcome use such as sponsorship type, intervention
      type, health condition, whether the trial was focused on pediatric patients,
      phase of trial and sample size were also extracted and explored with univariable
      and multivariable regressions. RESULTS: Four hundred and ninety-nine trials met
      inclusion criteria, 495 of which had complete information about hypothesized
      predictors. Only 36 out of 495 trials included an activity and participation
      outcome as part of the trial evaluation process. Both univariable and
      multivariable regression models showed that non-drug trials and late phase of
      trial (phase IV) showed the strongest likelihood with whether a trial would
      include an activity and participation outcome. DISCUSSION: Most registered
      clinical trials for children with chronic or ongoing medical conditions do not
      include a comprehensive approach to health outcomes assessment, especially drug
      trials and early phase trials. Outcome measures in pediatric clinical trials are
      lagging relative to World Health Organization standards for comprehensive health
      evaluation.

PMID- 24026629
TI  - The relationship between negative life events, psychological distress and life
      satisfaction: a population-based study.
AB  - PURPOSE: Negative life events may increase psychological distress and reduce life
      satisfaction (LS). This study investigates associations between negative life
      events and both positive and negative indicators of mental health and explores
      the extent to which these associations are buffered by sense of mastery and
      perceived social support. METHODS: Data were obtained from a large (N = 4,823),
      nationally representative sample of Norwegians aged 16 and older. Psychological
      distress was measured by The Hopkins Symptom Check List (HSCL-25), LS by a single
      question on overall satisfaction with life and negative life events by a 12-item
      list of threatening experiences. Moderating variables, sense of mastery and
      social support, were measured using standard instruments. RESULTS: Adjusting for
      age, sex, education and income, all of the negative life events were
      significantly associated with both psychological distress and LS, with the
      exception of events pertinent to bereavement. Of the life events examined,
      financial strain constituted the strongest predictor. Overall, negative life
      events were more closely associated with psychological distress than LS.
      Altogether, negative life events explained 22.3 and 11.4 % of the variance in
      psychological distress and LS, respectively. Sense of mastery, but not perceived
      social support, emerged as a moderating factor between financial strain and both
      psychological distress and LS. CONCLUSION: Negative life events are associated
      with higher psychological distress and lower LS, but the strength of the
      associations varies across events. The impact of financial strain and conflict
      appears particularly strong, but may be moderated by self-perceived mastery.

PMID- 24026630
TI  - Economic evaluation in short bowel syndrome (SBS): an algorithm to estimate
      utility scores for a patient-reported SBS-specific quality of life scale (SBS
      QoLTM).
AB  - PURPOSE: Condition-specific preference-based measures can offer utility data
      where they would not otherwise be available or where generic measures may lack
      sensitivity, although they lack comparability across conditions. This study aimed
      to develop an algorithm for estimating utilities from the short bowel syndrome
      health-related quality of life scale (SBS-QoLTM). METHODS: SBS-QoLTM items were
      selected based on factor and item performance analysis of a European SBS-QoLTM
      dataset and consultation with 3 SBS clinical experts. Six-dimension health states
      were developed using 8 SBS-QoLTM items (2 dimensions combined 2 SBS-QoLTM items).
      SBS health states were valued by a UK general population sample (N = 250) using
      the lead-time time trade-off method. Preference weights or 'utility decrements'
      for each severity level of each dimension were estimated by regression models and
      used to develop the scoring algorithm. RESULTS: Mean utilities for the SBS health
      states ranged from -0.46 (worst health state, very much affected on all
      dimensions) to 0.92 (best health state, not at all affected on all dimensions).
      The random effects model with maximum likelihood estimation regression had the
      best predictive ability and lowest root mean squared error and mean absolute
      error, and was used to develop the scoring algorithm. CONCLUSIONS: The preference
      weighted scoring algorithm for the SBS-QoLTM developed is able to estimate a wide
      range of utility values from patient-level SBS-QoLTM data. This allows estimation
      of SBS HRQL impact for the purpose of economic evaluation of SBS treatment
      benefits.

PMID- 24026631
TI  - Probabilistic mapping of the health status measure SF-12 onto the health utility
      measure EQ-5D using the US-population-based scoring models.
AB  - PURPOSE: Probabilistic mapping of the health status instrument SF-12 onto the
      health utility instrument EuroQol-5 dimensions (EQ-5D)-3L using the UK-population
      based scoring model showed encouraging results as compared to other mapping
      methods, although its predictive performance using the US-population-based EQ-5D
      scoring models has not been investigated. In addition, a new and improved US
      population-based EQ-5D scoring method has recently been developed and suggested
      for use in applications that required US societal health state values. In this
      study, we assessed predictive performance of the probabilistic mapping approach
      using the US-population-based scoring models on EQ-5D utility scores based on SF
      12 responses and compared the results with those of other mapping methods.
      METHODS: Using a sample of 19,678 adults from the 2003 Medical Expenditure Panel
      Survey, we evaluated the predictive performance of probabilistic mapping using
      Bayesian networks, response mapping using multinomial logistic regression,
      ordinary least squares, and censored least absolute deviations models by
      implementing a fivefold cross-validation method. The EQ-5D utility scores were
      generated using two US-population-based models: D1 and MM-OC. RESULTS: Overall,
      the probabilistic mapping approach using Bayesian networks consistently
      outperformed other mapping methods with mean squared errors (MSE) of 0.007 and
      0.007, mean absolute errors (MAE) of 0.057 and 0.039, and overall R (2) of 0.773
      and 0.770 for the US-population-based EQ-5D scoring D1 and MM-OC models,
      respectively. CONCLUSION: The probabilistic mapping approach can be useful to
      estimate EQ-5D utility scores from SF-12 responses with better predictive
      measures in terms of MSE, MAE, and R (2) than other common mapping methods.

PMID- 24026632
TI  - Quality of life among hazardous and harmful drinkers: EQ-5D over a 1-year follow
      up period.
AB  - PURPOSE: To investigate the ability of the EQ-5D to discriminate between levels
      of alcohol risk in a large sample of hazardous and harmful drinkers, and to
      explore the relationship between transitions between alcohol risk levels and
      changes in EQ-5D up to 12 months. METHODS: This is a web-based randomised
      controlled trial evaluating a novel intervention for hazardous and harmful
      alcohol consumption. EQ-5D scores were compared among groups of drinkers at
      baseline (low/medium/high risk according to self-reported past week alcohol
      consumption), and changes in EQ-5D scores were estimated as a function of changes
      in alcohol consumption level. RESULTS: Baseline EQ-5D scores were dominated by
      problems with anxiety/depression, which increased with alcohol risk level, whilst
      high-risk drinkers also experienced more problems with physical HRQoL dimensions.
      However, the tool demonstrated a considerable ceiling effect. At follow-up,
      despite considerable reductions in alcohol consumption across the sample,
      significant changes in aggregated EQ-5D index scores were only observed for high
      risk drinkers at baseline who reduced their drinking, with small improvements
      (0.04-0.06) compared to those who did not reduce. CONCLUSIONS: Our results
      suggest that the three-option EQ-5D may not be an optimal primary end point for
      measuring clinical and cost-effectiveness in randomised controlled trials of
      interventions among hazardous and harmful alcohol users, although further testing
      of the sensitivity of the tool in these populations is needed.

PMID- 24026633
TI  - How good is "very good"? Translation effect in the racial/ethnic variation in
      self-rated health status.
AB  - PURPOSE: To examine the influence of translation when measuring and comparing
      self-rated health (SRH) measured with five response categories (excellent, very
      good, good, fair, and poor), across racial/ethnic groups. METHODS: Using data
      from the California Health Interview Survey, which were administered in five
      languages, we analyzed variations in the five-category SRH across five
      racial/ethnic groups: non-Hispanic white, Latino, Chinese, Vietnamese, and
      Korean. Logistic regression was used to estimate independent effects of
      race/ethnicity, culture, and translation on SRH, after controlling for risk
      factors and other measures of health status. RESULTS: Latinos, Chinese,
      Vietnamese, and Koreans were less likely than non-Hispanic whites to rate their
      health as excellent or very good and more likely to rate it as good, fair, or
      poor. This racial/ethnic difference diminished when adjusting for acculturation.
      Independently of race/ethnicity, respondents using non-English surveys were less
      likely to answer excellent (OR = 0.24-0.55) and very good (OR = 0.30-0.34) and
      were more likely to answer fair (OR = 2.48-4.10) or poor (OR = 2.87-3.51), even
      after controlling for other measures of SRH. CONCLUSIONS: Responses to the five
      category SRH question depend on interview language. When responding in Spanish,
      Chinese, Korean, or Vietnamese, respondents are more likely to choose a lower
      level SRH category, "fair" in particular. If each SRH category measured in
      different languages is treated as equivalent, racial/ethnic disparities in SRH
      among Latinos and Asian subgroups, as compared to non-Hispanic whites, may be
      exaggerated.

PMID- 24026635
TI  - DNAzyme-functionalized gold nanoparticles for biosensing.
AB  - Recent progress in using DNAzyme-functionalized gold nanoparticles (AuNPs) for
      biosensing is summarized in this chapter. A variety of methods, including those
      for attaching DNA on AuNPs, detecting metal ions and small molecules by DNAzyme
      functionalized AuNPs, and intracellular applications of DNAzyme-functionalized
      AuNPs are discussed. DNAzyme-functionalized AuNPs will increasingly play more
      important roles in biosensing and many other multidisciplinary applications. This
      chapter covers the recent advancement in biosensing applications of DNAzyme
      functionalized gold nanoparticles, including the detection of metal ions, small
      molecules, and intracellular imaging.

PMID- 24026634
TI  - International development of an EORTC questionnaire for assessing health-related
      quality of life in chronic myeloid leukemia patients: the EORTC QLQ-CML24.
AB  - BACKGROUND: Health-related quality of life (HRQOL) is a key aspect for chronic
      myeloid leukemia (CML) patients. The aim of this study was to develop a disease
      specific HRQOL questionnaire for patients with CML to supplement the European
      Organization for Research and Treatment of Cancer (EORTC)-QLQ C30. PATIENTS AND
      METHODS: The process followed a predefined and systematic stepwise iterative
      process as defined by the EORTC guidelines for questionnaire development. The
      process was divided into 3 phases: (1) generation of relevant HRQOL issues, (2)
      operationalization of the HRQOL issues into a set of items, and (3) pretesting
      the questionnaire for relevance and acceptability. Descriptive statistics and
      psychometric analyses were also performed. RESULTS: Overall, 655 CML patients
      were enrolled in 10 countries including the USA and countries in Europe and Asia.
      Interviews with health-care professionals experienced in CML (n = 59) were also
      conducted. Results from the interviews, clinical experiences, and statistical
      analyses were used to develop the EORTC QLQ-CML24. The final module consists of
      24 items assessing the following aspects: symptom burden, impact on daily life
      and on worry/mood, body image problems, and satisfaction with care and with
      social life. Internal consistency, assessed with Cronbach's alpha coefficients,
      ranged from 0.73 to 0.83 for the proposed scales. CONCLUSION: The EORTC QLQ-CML24
      is an internationally developed HRQOL questionnaire for CML patients, and its
      implementation in clinical research and practice can provide important
      information to facilitate clinical decision-making.

PMID- 24026636
TI  - A well-circumscribed, painless abdominal mass.

PMID- 24026638
TI  - The reproduction of Enchytraeus sp.--technical improvement for the counting of
      juveniles.
AB  - Soil-dwelling annelids of the genus Enchytraeus are used in ecotoxicology for
      testing of chemicals mixed in artificial soil or for testing of wastes and soils
      of unknown quality. ISO 16387 describes a method for determining the effects of
      substances or contaminated soils on survival and reproduction of Enchytraeus
      albidus or of the smaller species Enchytraeus buchholzi or Enchy-traeus
      crypticus. After the total test duration of 6 (or 4) weeks, the juveniles hatched
      in the meantime are counted. There are several possible extraction techniques,
      which are always followed by counting the juveniles by hand, but none of them
      seems easy to handle. We proposed a new modification of the worm extraction
      method using flotation of fixed and stained juveniles followed by taking a
      photograph. The digital image of the juveniles is evaluated by computer
      processing. It makes the counting of juveniles much easier and less labor
      intensive. 

PMID- 24026637
TI  - Alpha-synuclein transmission and mitochondrial toxicity in primary human foetal
      enteric neurons in vitro.
AB  - Parkinson's disease (PD) is a multicentred neurodegenerative disorder
      characterised by the accumulation and aggregation of alpha-synuclein (alpha-syn)
      in several parts of the central nervous system. However, it is well established
      that PD can generate symptoms of constipation and other gastrointestinal problems
      and alpha-syn containing lesions have been identified in intestinal nerve cells.
      In this study, we show that alpha-syn can be taken up and accumulate in primary
      human foetal enteric neurons from the gastrointestinal tract and can be
      transferred between foetal enteric neurons. Impaired proteosomal/lysosomal
      degradation can promote the uptake and accumulation of alpha-syn in enteric
      neurons. Enteric neurons exposed to alpha-syn can also lead to impaired
      mitochondrial complex I activity, reduced mitochondrial function, and NAD(+)
      depletion culminating in cell death via energy restriction. These findings
      demonstrate neuron-to-neuron transmission of alpha-syn in enteric neurons,
      providing renewed evidence for Braak's hypothesis and the aetiology of PD. 

PMID- 24026639
TI  - Organised inpatient (stroke unit) care for stroke.
AB  - BACKGROUND: Organised stroke unit care is provided by multidisciplinary teams
      that exclusively manage stroke patients in a ward dedicated to stroke patients,
      with a mobile stroke team or within a generic disability service (mixed
      rehabilitation ward). OBJECTIVES: To assess the effect of stroke unit care
      compared with alternative forms of care for people following a stroke. SEARCH
      METHODS: We searched the trials registers of the Cochrane Stroke Group (January
      2013) and the Cochrane Effective Practice and Organisation of Care (EPOC) Group
      (January 2013), MEDLINE (2008 to September 2012), EMBASE (2008 to September 2012)
      and CINAHL (1982 to September 2012). In an effort to identify further published,
      unpublished and ongoing trials, we searched 17 trial registers (January 2013),
      performed citation tracking of included studies, checked reference lists of
      relevant articles and contacted trialists. SELECTION CRITERIA: Randomised
      controlled clinical trials comparing organised inpatient stroke unit care with an
      alternative service. After formal risk of bias assessment, we have now excluded
      previously included quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two
      review authors initially assessed eligibility and trial quality. We checked
      descriptive details and trial data with the co-ordinators of the original trials.
      MAIN RESULTS: We included 28 trials, involving 5855 participants, comparing
      stroke unit care with an alternative service. More-organised care was
      consistently associated with improved outcomes. Twenty-one trials (3994
      participants) compared stroke unit care with care provided in general wards.
      Stroke unit care showed reductions in the odds of death recorded at final (median
      one year) follow-up (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.69 to
      0.94; P = 0.005), the odds of death or institutionalised care (OR 0.78, 95% CI
      0.68 to 0.89; P = 0.0003) and the odds of death or dependency (OR 0.79, 95% CI
      0.68 to 0.90; P = 0.0007). Sensitivity analyses indicated that the observed
      benefits remained when the analysis was restricted to securely randomised trials
      that used unequivocally blinded outcome assessment with a fixed period of follow
      up. Outcomes were independent of patient age, sex, initial stroke severity or
      stroke type, and appeared to be better in stroke units based in a discrete ward.
      There was no indication that organised stroke unit care resulted in a longer
      hospital stay. AUTHORS' CONCLUSIONS: Stroke patients who receive organised
      inpatient care in a stroke unit are more likely to be alive, independent, and
      living at home one year after the stroke. The benefits were most apparent in
      units based in a discrete ward. We observed no systematic increase in the length
      of inpatient stay.

PMID- 24026640
TI  - Effects of aspirin on the ERK and PI3K/Akt signaling pathways in rats with acute
      pulmonary embolism.
AB  - Inflammation contributes to acute pulmonary embolism (APE). However, the
      contributions of the extracellular signal-regulated protein kinases (ERK) and
      phosphoinositide 3 kinase/protein kinase B (PI3K/Akt) signaling pathways have not
      yet been elucidated. The aim of this study was to examine the effects of aspirin
      on ERK and PI3K/Akt signaling in a rat model of APE and evaluate the prognostic
      values of brain natriuretic peptide (BNP), troponin (TnT) and D-Dimer. A total of
      108 Sprague-Dawley rats were assigned into the control, sham, model and low-,
      medium- and high-dose aspirin (150, 300 and 600 mg/kg, respectively) groups. In
      each group, six rats were sacrificed 6, 24 and 72 h subsequent to the induction
      of APE to collect the lungs and serum. Western blot analysis was used to assess
      ERK, PI3K and Akt expression; enzyme-linked immunosorbent assay (ELISA) was used
      to analyze BNP, TnT and D-Dimer levels; and changes in lung pathology were
      evaluated using hematoxylin and eosin (H&E) staining. The results showed that ERK
      and PI3K levels were decreased in the control, sham and the three aspirin groups
      at all time-points compared with the model group (P<0.01). The exception was in
      the medium-dose aspirin group at 24 h. The serum levels of BNP, TnT and D-Dimer
      were lower in the control and sham groups at all time-points compared with the
      model group (P<0.05). Furthermore, the levels of BNP, TnT and D-Dimer levels were
      decreased in the aspirin-treated groups (P<0.05) and markedly increased in the
      model group (P<0.05) at 24 h compared with the levels at 6 h. Pulmonary embolism,
      alveolar wall necrosis and hemorrhage were observed in the model group 6, 24 and
      72 h subsequent to the induction of the model. However, congestion and
      inflammation were attenuated following aspirin treatment. In conclusion, aspirin
      reduces lung damage and improves prognosis. Decreased ERK, PI3K and Akt
      expression in the lungs and reduced levels of BNP, TnT and D-Dimer may be
      important factors in the effects observed.

PMID- 24026641
TI  - New insights into modulation of thrombin formation.
AB  - Thrombin is a pleiotropic enzyme that regulates hemostasis and nonhemostatic
      functions, including an array of actions within and on the vasculature.
      Physiologically, thrombin generation serves mainly to protect against thrombosis,
      but also to maintain vascular endothelial integrity. This protective effect is
      mediated in part through generation of anticoagulant enzymes, including activated
      protein C, formed on the action of thrombin on the endothelial receptor
      thrombomodulin. Partly, thrombin's vascular effects are effectuated through
      interaction with protease-activated receptors on various cell types.
      Pathophysiologically, downregulation and shedding of anticoagulant-acting
      receptors such as thrombomodulin and endothelial protein C receptor may
      contribute to a shift in activities of thrombin towards thrombogenic and
      proinflammatory actions. This shift may typically occur in the process of
      atherosclerosis, leading to a proatherogenic direction of the effects of
      thrombin. Therapeutically, the long-term inhibition of thrombin may create new
      ways of reducing atherosclerosis burden, altering the plaque phenotype. 

PMID- 24026656
TI  - Expression of Rac-1 related to tumor depth, lymph node metastasis and patient
      prognosis in esophageal squamous cell carcinoma.
AB  - Rac-1, which is a member of the Rho guanosine triphosphatase (GTPase) family, has
      been demonstrated to play an important role in cancer invasion and metastasis. In
      this study, we investigated the clinical and prognostic significance of Rac-1 in
      esophageal squamous cell carcinoma (ESCC). The protein and messenger ribonucleic
      acid (mRNA) levels of Rac-1 in normal esophageal epithelia cells and paired ESCC
      tissues were examined by Western blot and reverse transcription polymerase chain
      reaction. The results showed that Rac-1 was upregulated at the protein and mRNA
      levels in ESCC cancerous specimens compared with normal esophageal tissues. We
      then examined the correlation between Rac-1 expression and clinicopathological
      features using immunochemical analysis of 233 surgically resected ESCC. Rac-1
      protein was expressed in 228 (97.85%) cancer tissues with cytoplasm staining, and
      there were significant correlations between Rac-1 expression and tumor location
      (P = 0.045), tumor stage (P = 0.020), tumor depth (P = 0.023) and lymph node
      metastasis (P = 0.009). The overall survival and disease-free rates of ESCC
      patients with high Rac-1 expression were much lower than those with low Rac-1
      expression (P < 0.001; P < 0.001, respectively). Multivariate analysis showed
      that high Rac-1 expression and lymph node metastasis were two independent factors
      for poor survival (P < 0.001; P < 0.001, respectively). The results in this study
      indicate, for the first time, that Rac-1 is involved in the invasion and
      metastatic progression of ESCC and may be a potential marker for evaluating the
      prognosis of ESCC patients and a therapy target for ESCC.

PMID- 24026658
TI  - Time to prostate specific antigen (PSA) nadir may predict rapid relapse in men
      with metastatic castration-resistant prostate cancer (CRPC) receiving docetaxel
      chemotherapy.
AB  - Docetaxel has been shown to improve survival in patients with metastatic castrate
      resistant prostate cancer (mCRPC). There is no clear consensus regarding the
      optimum duration of chemotherapy. If patients at greater risk of rapid disease
      relapse could be identified when on chemotherapy, appropriate follow-up
      strategies could be put into place. The aim of our study was to find prostate
      specific antigen (PSA) characteristics that predict a shorter disease response to
      docetaxel chemotherapy. Data from 41 consecutive mCRPC patients treated with
      three-weekly docetaxel chemotherapy at a single centre between February 2010 and
      February 2012 were retrospectively analysed. All patients had >=50% reduction in
      their PSA with chemotherapy. The relationship between time to PSA nadir (TTN) and
      PSA halving time with time to PSA progression and overall chemotherapy response
      duration was analysed. TTN was a strong predictor of the duration of chemotherapy
      response and time to PSA progression. When TTN was >=16 weeks, the mean duration
      of response to chemotherapy was 37.5 weeks compared to 19.9 weeks when TTN <16
      weeks (95% CI, 12.66-22.60; p = 1.239 * 10(-8)). The mean time to PSA progression
      was 12.8 weeks if TTN was >=16 weeks and 8.2 weeks TTN was <16 weeks (95% CI 0.63
      8.60; p = 0.024). We observed that a TTN from the initiation of chemotherapy of
      <16 weeks for patients with mCRPC is an independent predictor of shorter duration
      of response and shorter progression-free survival.

PMID- 24026657
TI  - Elevated expression of tumor miR-222 in pancreatic cancer is associated with Ki67
      and poor prognosis.
AB  - Pancreatic cancer is known for its bad prognosis. Micro-RNAs mis-expressions are
      associated with various human cancers and offer new candidate targets for
      diagnostic and therapeutic strategies. Micro-RNA-222 has been shown to play a
      crucial role in cancer cell proliferation in recent studies. However, its
      correlations with the clinicopathological characters of pancreatic cancer still
      remain unclear. Through a prospective study of 60 pairs of pancreatic cancer
      tissues, adjacent normal tissues were examined by quantitative reverse
      transcription polymerase chain reaction. The correlation between the expression
      of micro-RNA-222 and clinico-pathological characters was performed using the two
      sample Student's t test. The survival correlations were analyzed by the Kaplan
      Meier method and the Cox's proportional hazards model. Results showed that the
      expression levels of micro-RNA-222 were significantly elevated in the pancreatic
      cancer tissue compared with that in adjacent normal tissue. In addition, the
      overexpression of the tissue micro-RNA-222 strongly related to the expression
      level of Ki67. Finally, Cox's proportional hazards model analysis confirmed that
      micro-RNA-222 high expression level was an independent predictor of poor
      prognosis. This study provides the first evidence of a potential link between
      Ki67 and micro-RNA-222, which are both relevant to cell proliferation. Our data
      suggest the potential of micro-RNA-222 as a prognostic biomarker for the
      pancreatic cancer. 

PMID- 24026659
TI  - Prognostic value of preoperative peripheral neutrophil-to-lymphocyte ratio in
      patients with HBV-associated hepatocellular carcinoma after radical hepatectomy.
AB  - Neutrophil-to-lymphocyte ratio (NLR), an inflammation index, is considered a
      prognostic predictor of hepatocellular carcinoma (HCC). This study aimed to
      evaluate the prognostic value of preoperative peripheral NLR in patients with
      hepatitis B virus (HBV)-associated HCC after radical hepatectomy. Clinical data
      were collected from patients with HBV-associated HCC who underwent radical
      hepatectomy. NLR was calculated from lymphocyte and neutrophil counts on
      preoperative routine blood tests. Demographics, laboratory analyses, and
      histopathological data were analyzed. A total of 282 patients were selected and
      divided by the cutoff NLR value of 2. Multivariate analysis showed that NLR > 2
      was an independent prognostic predictor of poor disease-free survival [hazard
      ratio (HR) = 1.362; 95% confidence interval (CI) 1.025-1.811; P = 0.033] and
      overall survival (HR = 1.434; 95% CI 1.044-1.970; P = 0.023). NLR had a good
      predictive value for prognosis in patients with HBV-associated HCC who had normal
      serum AFP level. These results suggested that NLR is an independent indicator of
      both disease-free survival and overall survival in patients with HBV-associated
      HCC after radical hepatectomy, including AFP-normal patients.

PMID- 24026660
TI  - Orbital and ocular adnexal Mucosa-Associated Lymphoid Tissue (MALT) lymphomas: a
      single-center 10-year experience.
AB  - Orbital and ocular andexal Mucosa-Associated Lymphoid Tissue Lymphoma (MALT) or
      ocular adnexal MALT lymphoma (OAML) is the most common of all eye non-Hodgkin
      lymphomas. Autoimmune inflammatory disorders and chronic infections are important
      etiological factors and CD5 and CD43 (sialophorin) tumor markers are significant
      negative prognostic factors. Disease signs and symptoms can occur a long time
      before diagnosis. Varieties of treatment options are available. The aim of this
      retrospective analysis was to compare the efficiency of different treatment
      options and to investigate disease outcome. Twenty OAML patients, diagnosed in
      the Clinic of Hematology, Clinical Centre of Serbia, between 2003 and 2013, were
      enrolled. In most cases, OAML developed in the eighth decade with greater
      incidence in the male population. Median age was 67.5 years. The median period
      between the appearance of local signs and symptoms and diagnosis was 7 months.
      The dominant sign at presentation was swelling of involved tissue (40%). The most
      common was orbital involvement (55%). All patients had localized disease.
      Observed laboratory parameters on presentation showed low disease activity.
      Sialophorin prognostic significance was not registered. Our patients were
      initially treated differently but there was no significant difference in
      progression-free survival (PFS) due to initial treatment option (p = 0.2957).
      Median PFS was 22 months (3-89), and 5-year PFS was 60%. Median overall survival
      (OS) was 43 months (1-105) and 5-year OS 95%. Eight patients (40%) relapsed and
      one patient died due to non-hematological complications. In our experience, most
      modern induction treatment options appear to result in the same, favorable
      outcome.

PMID- 24026661
TI  - High level of p37delta-mRNA relative to p110delta-mRNA in neuroblastoma tumors
      correlates with poor patient survival.
AB  - Alterations in the PI3K/Akt pathway, a pathway that promotes proliferation and
      oncogenic transformation, are common in various cancers. In neuroblastoma,
      activation of Akt is correlated with aggressive disease although mutations in
      genes of this pathway are rare. Previous findings include a few mutations in
      PIK3CD, the gene encoding PI3K catalytic subunit delta, p110delta. We recently
      reported that an alternatively spliced form of p110delta, called p37delta, had
      cell proliferative properties and was over-expressed in ovarian and colorectal
      tumors. Here, we investigated p37delta in neuroblastoma primary tumors of
      different stages using qPCR (TaqMan) for gene expression analysis (46 samples)
      and Western blot for protein analysis (22 samples). Elevated levels of both
      p37delta-mRNA and p110delta-mRNA were detected in metastasizing neuroblastoma
      tumors compared to normal adrenal gland (P < 0.05), and higher expression of
      p37delta-mRNA relative to p110delta-mRNA in neuroblastoma non-survivor patients
      compared to survivors (P < 0.01). p37delta-Protein levels but not p110delta
      levels correlated with increased pAKT(T308) and pERK levels. The p37delta-mRNA
      levels did not correlate with the protein levels, indicating major regulation at
      the translational/protein level. Deregulation of signaling pathways is a hallmark
      of cancer development. Here, we show that p37delta, a kinase-dead isoform of the
      PI3K catalytic subunit p110delta, is over-expressed in neuroblastoma tumors, and
      that it correlates with the activation of both PI3K/Akt- and RAS-signaling
      pathways.

PMID- 24026662
TI  - CRM1 is a novel independent prognostic factor for the poor prognosis of gastric
      carcinomas.
AB  - Gastric cancer (GC) is a highly aggressive malignant tumor. Its high mortality
      rate prompts the urgent need for novel therapeutic agents. The aim of this study
      is to detect the expression of CRM1 in GC, which has not been reported to date.
      The expression of CRM1 in GC and adjacent noncancerous tissues (ANCT) of
      gastrectomy specimens from 120 GC patients was measured by immunohistochemistry.
      In addition, correlations between the CRM1 staining and the clinicopathologic
      features as well as survival were analyzed. Positive expression rates of CRM1 in
      GC and ANCT were 57.8 and 6.7%, respectively. High expression of CRM1 was
      significantly associated with increased serum level of carcinoma embryonic
      antigen (CEA, P = 0.02) but not associated with that of carbohydrate antigen 19-9
      (P = 0.38). CRM1 levels were correlated with more advanced tumor stages (P =
      0.01), positive Her2 status (P = 0.01), and distant metastasis (P = 0.02).
      Univariate analysis showed that CEA (P = 0.0076), TNM stage (P = 0.0001),
      metastasis (P = 0.027), and CRM1 expression (P = 0.0019) were significant risk
      factors affecting overall survival of GC patients. The multivariate analysis
      indicated that the CRM1 was an independent indicator for GC survival (P =
      0.0048). The current results indicated that CRM1 expressed in a subpopulation of
      GC with aggressive behavior and could serve as a prognosis marker for poor
      outcome.

PMID- 24026663
TI  - Clinical implications of the tumor-infiltrating lymphocyte subsets in colorectal
      cancer.
AB  - Though the total lymphocyte density has been implicated in the pathogenesis of
      colorectal cancer (CRC), the clinical implications of lymphocyte subsets in CRC
      patients remain unclear yet. In this study, we used tissue microarrays and
      immunohistochemistry to evaluate the density of tumor-infiltrating CD4(+) and
      CD8(+) T cells as well as CD20(+) B cells in the central region and the invasive
      margin (IM) of tumor tissue from 67 CRC patients and then analyzed the clinical
      implications. We found that the subsets of tumor-infiltrating lymphocyte had no
      relationship with patients' age, tumor size, N category, and tumor stage.
      However, the density of B cells in the tumor center (TC) of colorectal patients
      in T1/T2 category was much higher than that of patients in T3/T4 category (P =
      0.008). In addition, patients in M0 category had a higher density of CD8(+) T
      cells in the IM but not in the TC compared to patients in M1 category (P = 0.03).
      Results in this study demonstrate that higher CD8(+) T cell density in the IM of
      tumor is associated with lower tumor metastasis and higher B cell density in TC
      is associated with lower tumor T category. The results also suggest that the
      analysis of infiltrating lymphocyte subsets is important for understanding the
      detailed mechanisms of tumor pathogenesis and exploring potential interventions
      for the tumor.

PMID- 24026664
TI  - p53 immunohistochemical expression and patient prognosis in esophageal squamous
      cell carcinoma.
AB  - It is generally accepted that overexpression of p53 protein is associated with
      poor prognosis in gastric, lung, and other types of cancer. However, the
      prognostic significance of p53 aberrations in esophageal cancer remains unclear.
      This is the largest study (n = 266) examining clinical and prognostic features of
      p53 immunohistochemical expression in esophageal squamous cell carcinoma. In 139
      (52%) esophageal tumors, nuclear immunoreactivity for p53 protein was detected.
      p53 aberrant expression was not associated with sex, age, preoperative treatment,
      TNM stage, or histological grade. Furthermore, p53 expression did not correlate
      with disease-free survival (P = 0.73) or overall survival (P = 0.62). In
      addition, no significant modification effect by any of the covariates in the
      survival analysis was observed (all P > 0.15). In conclusion, our large-scale
      study demonstrates that p53 expression has no impact on the prognosis of
      esophageal squamous cell carcinoma.

PMID- 24026666
TI  - A neutral Fe(III) compound exhibiting a two-step spin transition and dielectric
      anomalies.
AB  - The mononuclear ferric compound Fe(H-5-Cl-thsa-Me)(5-Cl-thsa-Me).H2O () was
      synthesized and characterized using powder/single-crystal X-ray diffraction,
      Mossbauer spectroscopy, differential scanning calorimetry (DSC), and magnetic
      susceptibility measurements. This photo-responsive compound shows reversible, two
      step spin-crossover behaviour. Moreover, dielectric anomalies were observed
      during the spin transitions, demonstrating the multifunctional properties of
      compound . 

PMID- 24026665
TI  - A genetical genomics approach reveals new candidates and confirms known candidate
      genes for drip loss in a porcine resource population.
AB  - In this study lean meat water-holding capacity (WHC) of a Duroc * Pietrain (DuPi)
      resource population with corresponding genotypes and transcriptomes was
      investigated using genetical genomics. WHC was characterized by drip loss
      measured in M. longissimus dorsi. The 60K Illumina SNP chips identified genotypes
      of 169 F2 DuPi animals. Whole-genome transcriptomes of muscle samples were
      available for 132 F2 animals using the Affymetrix 24K GeneChip(r) Porcine Genome
      Array. Performing genome-wide association studies of transcriptional profiles,
      which are correlated with phenotypes, allows elucidation of cis- and trans
      regulation. Expression levels of 1,228 genes were significantly correlated with
      drip loss and were further analyzed for enrichment of functional annotation
      groups as defined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes
      pathways. A hypergeometric gene set enrichment test was performed and revealed
      glycolysis/glyconeogenesis, pentose phosphate pathway, and pyruvate metabolism as
      the most promising pathways. For 267 selected transcripts, expression
      quantitative trait loci (eQTL) analysis was performed and revealed a total of
      1,541 significant associations. Because of positional accordance of the gene
      underlying transcript and the eQTL location, it was possible to identify eight
      eQTL that can be assumed to be cis-regulated. Comparing the results of gene set
      enrichment and the eQTL detection tests, molecular networks and potential
      candidate genes, which seemed to play key roles in the expression of WHC, were
      detected. The alpha-1-microglobulin/bikunin precursor (AMBP) gene was assumed to
      be cis-regulated and was part of the glycolysis pathway. This approach supports
      the identification of trait-associated SNPs and the further biological
      understanding of complex traits. 

PMID- 24026667
TI  - A cigarette component acrolein induces accelerated senescence in human diploid
      fibroblast IMR-90 cells.
AB  - Cigarette smoking causes various diseases, including lung cancer and
      cardiovascular disease, and reduces life span, though the mechanisms are not well
      understood. We hypothesize that smoking may cause cellular mitochondrial
      dysfunction and oxidative stress, leading to aging acceleration. In the present
      study, we tested the effects of acrolein, a major representative smoking
      toxicant, on human lung fibroblast IMR-90 cells with regard to cellular
      senescence, oxidative stress, and mitochondrial function. The results showed that
      subacute treatment with low dose of acrolein induces the following events
      compared to the control cells: cell senescence demonstrated by increases in the
      activity of beta-galactosidase, the higher expression of p53 and p21, decreases
      in DNA synthesis, Sirt1 expression, and telomere length; oxidative stress
      occurred as the increases in the production of reactive oxygen species, DNA
      damage, and protein oxidation; and mitochondrial dysfunction shown as decreases
      in the mitochondrial membrane potential, mitochondrial biogenesis regulator PGC-1
      alpha and mitochondria complex I, II, III, and V. These results suggest that
      acrolein may accelerate aging through the mechanism of increasing oxidative
      stress and mitochondrial dysfunction. 

PMID- 24026668
TI  - Early down regulation of the glial Kir4.1 and GLT-1 expression in pericontusional
      cortex of the old male mice subjected to traumatic brain injury.
AB  - Astroglia play multiple roles in brain function by providing matrix to neurons,
      secreting neurotrophic factors, maintaining K(+) and glutamate homeostasis and
      thereby controlling synaptic plasticity which undergoes alterations during aging.
      K(+) and glutamate homeostasis is maintained by astrocytes membrane bound
      inwardly rectifying K(+) channel (Kir4.1) and glutamate transporter-1 (GLT-1 or
      EAAT-2) proteins, respectively in the synapse and their expression may be altered
      due to traumatic brain injury (TBI). Also, it is not well understood whether this
      change is age dependent. To find out this, TBI was experimentally induced in
      adult and old male AKR strain mice using CHI technique, and expression of the
      Kir4.1 and GLT-1 in the pericontusional cortex at various time intervals was
      studied by Western blotting and semi quantitative RT-PCR techniques. Here, we
      report that expression of both Kir4.1 and GLT-1 genes at transcript and protein
      levels is significantly down regulated in the pericontusional ipsi-lateral cortex
      of old TBI mice as compared to that in the adult TBI mice as function of time
      after injury. Further, expression of both the genes starts decreasing early in
      old mice i.e., from the first hour after TBI as compared to that starts from
      fourth hour in adult TBI mice. Thus TBI affects expression of Kir4.1 and GLT-1
      genes in age- and time dependent manner and it may lead to accumulations of more
      K(+) and glutamate early in the synapse of old mice as compared to adult. This
      may be implicated in the TBI induced early and severe neuronal depolarization and
      excito-neurotoxicity in old age. 

PMID- 24026669
TI  - Epstein-barr virus diversity in immunocompetent healthy persons: reassessment of
      the distribution of genetic variants.
AB  - Epstein-Barr virus (EBV) has many strains; however, it remains unclear whether a
      causal relationship exists between different regions and viral genetic variants
      in healthy persons. This study was designed to examine the relationship between
      EBV strains in tonsils and adenoids and peripheral blood lymphocytes of the same
      individuals using different measurements of EBV strain polymorphism. This study
      examined whether EBV contains two or three copies of a tandem repeat sequence in
      the first intron of the BZLF-1 gene. The genotype of the virus from P3HR-1,
      designated Z*, yielded a 415-bp product, and this was distinguished from the
      smaller, 386-bp product obtained with the B95-8 virus, designated the Z genotype.
      Simultaneous sequence infections with Z and Z* genotypes were also detected in
      one of the tonsils examined, suggesting that more than one strain or variant of
      EBV genotype may be present in a specimen from the same subject. Co-infection
      with Z and Z* was recognized in two subjects, so variation of the EBV gene may be
      seen in at least two different strains of EBV. It was seen that Z and Z* strain
      infected cells are constantly in flux through lymph nodes and/or the blood stream
      in healthy persons; therefore, these results indicated that EBV genome variants
      probably show no specific tissue distribution.

PMID- 24026670
TI  - The non-primate hepacivirus 5' untranslated region possesses internal ribosomal
      entry site activity.
AB  - The 5' untranslated region (5'UTR) of the recently described non-primate
      hepacivirus (NPHV) contains a region with sequence homology to the internal
      ribosomal entry site (IRES) of hepatitis C virus (HCV) and GB virus B (GBV-B).
      Here, we demonstrated internal translation initiation by the NPHV 5'UTR in a
      bicistronic vector. An RNA stem-loop upstream of the NPHV IRES was structurally
      distinct from corresponding regions in HCV and GBV-B, and was not required for
      IRES function. Insertion of the NPHV stem-loop into the corresponding region of
      the HCV 5'UTR within the HCV subgenomic replicon significantly impaired RNA
      replication, indicating that long-range interactions between the 5'UTR and cis
      acting downstream elements within the NPHV genome are not interchangeable with
      those of HCV. Despite similarities in IRES structure and function between
      hepaciviruses, replication elements in the NPHV 5'UTR appear functionally
      distinct from those of HCV. 

PMID- 24026671
TI  - Capsid-binding retrovirus restriction factors: discovery, restriction specificity
      and implications for the development of novel therapeutics.
AB  - The development of drugs against human immunodeficiency virus type 1 infection
      has been highly successful, and numerous combinational treatments are currently
      available. However, the risk of the emergence of resistance and the toxic effects
      associated with prolonged use of antiretroviral therapies have emphasized the
      need to consider alternative approaches. One possible area of investigation is
      provided by the properties of restriction factors, cellular proteins that protect
      organisms against retroviral infection. Many show potent viral inhibition. Here,
      we describe the discovery, properties and possible therapeutic uses of the group
      of restriction factors known to interact with the capsid core of incoming
      retroviruses. This group comprises Fv1, TRIM5alpha and TRIMCypA: proteins that
      all act shortly after virus entry into the target cell and block virus
      replication at different stages prior to integration of viral DNA into the host
      chromosome. They have different origins and specificities, but share general
      structural features required for restriction, with an N-terminal multimerization
      domain and a C-terminal capsid-binding domain. Their overall efficacy makes it
      reasonable to ask whether they might provide a framework for developing novel
      antiretroviral strategies. 

PMID- 24026673
TI  - In vitro replication competence of a hepatitis B genotype D/A recombinant virus:
      dissimilar biological behaviour regarding its parental genotypes.
AB  - Hepatitis B virus (HBV) DNA recombinants contribute to ~30% of the overall full
      length sequences already deposited in GenBank. However, their biological
      behaviour has not been analysed so far. In this study, the in vitro replication
      kinetics of the first D/A recombinant from the American continent differed from
      its parental genotypes, exhibiting higher extracellular levels of HBV DNA and
      hepatitis B e antigen. Southern blots of intracellular core-associated HBV DNA
      were in agreement with such results. Because this recombinant was obtained from
      an Argentinian injecting drug user belonging to a vulnerable community, these
      results are of singular relevance for regional public health. Further in vivo
      studies are urgently needed to determine the pathogenicity of these replicative
      competent clones.

PMID- 24026672
TI  - Generation of a replication-competent simian-human immunodeficiency virus, the
      neutralization sensitivity of which can be enhanced in the presence of a small
      molecule CD4 mimic.
AB  - Simian-human immunodeficiency virus (SHIV) carrying the envelope from the clade B
      clinical human immunodeficiency virus type 1 (HIV-1) isolate MNA, designated SHIV
      MNA, was generated through intracellular homologous recombination. SHIV MNA
      inherited biological properties from the parental HIV-1, including CCR5 co
      receptor preference, resistance to neutralization by the anti-V3 loop mAb KD-247
      and loss of resistance in the presence of the CD4-mimic small-molecule YYA-021.
      SHIV MNA showed productive replication in rhesus macaque PBMCs. Experimental
      infection of a rhesus macaque with SHIV MNA caused a transient but high titre of
      plasma viral RNA and a moderate antibody response. Immunoglobulin in the plasma
      at 24 weeks post-infection was capable of neutralizing SHIV MNA in the presence
      but not in the absence of YYA-021. SHIV MNA could serve a model for development
      of novel therapeutic interventions based on CD4-mimic-mediated conversion of
      envelope protein susceptible to antibody neutralization. 

PMID- 24026674
TI  - Prednisolone combined with adjunctive immunosuppression is not superior to
      prednisolone alone in terms of efficacy and safety in giant cell arteritis: meta
      analysis.
AB  - To conduct a meta-analysis of published data of the effectiveness of drug
      treatment in giant cell arteritis (GCA) to provide evidence to support the
      optimal use of glucocorticoids (GCs) and adjunct therapy. MEDLINE, CENTRAL and
      EMBASE searches were used to identify randomised control trials on the treatment
      of GCA. Studies included were trials in which: (1) the participants were
      classified as having GCA by the 1990 ACR criteria or biopsy proven disease; (2)
      parallel-group randomised control of at least 16 weeks duration had been
      conducted with at least 20 participants; (3) the design included either
      alternative adjunct immunosuppressant regimens, alternative GCs dosing or routes
      of administration; and (4) outcome data was included on either relapse rates or
      rates of infection. One thousand eight hundred thirty-six articles were
      retrieved, of which only 37 met the primary inclusion criteria. Sixteen of these
      studies reported some information about the GCs or adjuvant regimen used. Only
      ten studies were of sufficient quality to be included in the meta-analysis.
      Together these comprised 638 participants of which 72 % were female. Three
      studies compared various GCs regimens, with two comparing IV GCs, the latter
      showing a marginal benefit with respect to relapse (risk ratio (RR) = 0.78, 95 %
      CI = 0.54 to 1.12) but a greater risk of infection (RR = 1.58, 95 % CI = 0.90 to
      2.78). Another three used methotrexate as an adjunctive agent and showed marginal
      benefit with respect to relapse (RR = 0.85, 95 % CI = 0.66 to 1.11). The
      remaining four trials compared prednisolone to dapsone, infliximab, adalimumab
      and hydroxychloroquine, respectively. There are various clinical trials of
      varying quality. The results from this meta-analysis show that the use of adjunct
      agents is not associated with improved outcome.

PMID- 24026675
TI  - Validation of the auto-inflammatory diseases activity index (AIDAI) for
      hereditary recurrent fever syndromes.
AB  - OBJECTIVES: To validate the Auto-Inflammatory Diseases Activity Index (AIDAI) in
      the four major hereditary recurrent fever syndromes (HRFs): familial
      Mediterranean fever (FMF), mevalonate kinase deficiency (MKD), tumour necrosis
      factor receptor-associated periodic syndrome (TRAPS) and cryopyrin-associated
      periodic syndromes (CAPS). METHODS: In 2010, an international collaboration
      established the content of a disease activity tool for HRFs. Patients completed a
      1-month prospective diary with 12 yes/no items before a clinical appointment
      during which their physician assessed their disease activity by a questionnaire.
      Eight international experts in auto-inflammatory diseases evaluated the patient's
      disease activity by a blinded web evaluation and a nominal group technique
      consensus conference, with their consensus judgement considered the gold
      standard. Sensitivity/specificity/accuracy measures and the ability of the score
      to discriminate active from inactive patients via the best cut-off score were
      calculated by a receiver operating characteristic analysis. RESULTS: Consensus
      was achieved for 98/106 (92%) cases (39 FMF, 35 CAPS, 14 TRAPS and 10 MKD), with
      26 patients declared as having inactive disease and 72 as having active disease.
      The median total AIDAI score was 14 (range=0-175). An AIDAI cut-off score >=9
      discriminated active from inactive patients, with
      sensitivity/specificity/accuracy of 89%/92%/90%, respectively, and an area under
      the curve of 98% (95% CI 96% to 100%). CONCLUSIONS: The AIDAI score is a valid
      and simple tool for assessing disease activity in FMF/MKD/TRAPS/CAPS. This tool
      is easy to use in clinical practice and has the potential to be used as the
      standard efficacy measure in future clinical trials.

PMID- 24026676
TI  - Sugar-sweetened beverage consumption: a risk factor for prevalent gout with
      SLC2A9 genotype-specific effects on serum urate and risk of gout.
AB  - OBJECTIVE: Consumption of high fructose corn syrup (HFCS)-sweetened beverages
      increases serum urate and risk of incident gout. Genetic variants in SLC2A9, that
      exchanges uric acid for glucose and fructose, associate with gout. We tested
      association between sugar (sucrose)-sweetened beverage (SSB) consumption and
      prevalent gout. We also tested the hypothesis that SLC2A9 genotype and SSB
      consumption interact to determine gout risk. METHODS: Participants were 1634 New
      Zealand (NZ) European Caucasian, Ma-ori and Pacific Island people and 7075
      European Caucasians from the Atherosclerosis Risk in Communities (ARIC) study. NZ
      samples were genotyped for rs11942223 and ARIC for rs6449173. Effect estimates
      were multivariate adjusted. RESULTS: SSB consumption increased gout risk. The OR
      for four drinks/day relative to zero was 6.89 (p=0.045), 5.19 (p=0.010) and 2.84
      (p=0.043) for European Caucasian, Ma-ori and Pacific Islanders, respectively.
      With each extra daily SSB serving, carriage of the gout-protective allele of
      SLC2A9 associated with a 15% increase in risk (p=0.078), compared with a 12%
      increase in non-carriers (p=0.002). The interaction term was significant in
      pooled (pInteraction=0.01) but not meta-analysed (pInteraction=0.99) data. In
      ARIC, with each extra daily serving, a greater increase in serum urate protective
      allele carriers (0.005 (p=8.7*10(-5)) compared with 0.002 (p=0.016) mmol/L)
      supported the gout data (pInteraction=0.062). CONCLUSIONS: Association of SSB
      consumption with prevalent gout supports reduction of SSB in management. The
      interaction data suggest that SLC2A9-mediated renal uric acid excretion is
      physiologically influenced by intake of simple sugars derived from SSB, with SSB
      exposure negating the gout risk discrimination of SLC2A9.

PMID- 24026677
TI  - The familial dementia gene revisited: a missense mutation revealed by whole-exome
      sequencing identifies ITM2B as a candidate gene underlying a novel autosomal
      dominant retinal dystrophy in a large family.
AB  - Inherited retinal diseases are a group of clinically and genetically
      heterogeneous disorders for which a significant number of cases remain
      genetically unresolved. Increasing knowledge on underlying pathogenic mechanisms
      with precise phenotype-genotype correlation is, however, critical for
      establishing novel therapeutic interventions for these yet incurable
      neurodegenerative conditions. We report phenotypic and genetic characterization
      of a large family presenting an unusual autosomal dominant retinal dystrophy.
      Phenotypic characterization revealed a retinopathy dominated by inner retinal
      dysfunction and ganglion cell abnormalities. Whole-exome sequencing identified a
      missense variant (c.782A>C, p.Glu261Ala) in ITM2B coding for Integral Membrane
      Protein 2B, which co-segregates with the disease in this large family and lies
      within the 24.6 Mb interval identified by microsatellite haplotyping. The
      physiological role of ITM2B remains unclear and has never been investigated in
      the retina. RNA in situ hybridization reveals Itm2b mRNA in inner nuclear and
      ganglion cell layers within the retina, with immunostaining demonstrating the
      presence of the corresponding protein in the same layers. Furthermore, ITM2B in
      the retina co-localizes with its known interacting partner in cerebral tissue,
      the amyloid beta precursor protein, critical in Alzheimer disease
      physiopathology. Interestingly, two distinct ITM2B mutations, both resulting in a
      longer protein product, had already been reported in two large autosomal dominant
      families with Alzheimer-like dementia but never in subjects with isolated retinal
      diseases. These findings should better define pathogenic mechanism(s) associated
      with ITM2B mutations underlying dementia or retinal disease and add a new
      candidate to the list of genes involved in inherited retinal dystrophies.

PMID- 24026678
TI  - Extensive transcriptional complexity during hypoxia-regulated expression of the
      myoglobin gene in cancer.
AB  - Recently, the ectopic expression of myoglobin (MB) was reported in human
      epithelial cancer cell lines and breast tumor tissues, where MB expression
      increased with hypoxia. The better prognosis of MB-positive breast cancer
      patients suggested that the globin exerts a tumor-suppressive role, possibly by
      impairing mitochondrial activity in hypoxic breast carcinoma cells. To better
      understand MB gene regulation in cancer, we systematically investigated the
      architecture of the human MB gene, its transcripts and promoters. In silico
      analysis of transcriptome data from normal human tissues and cancer cell lines,
      followed by RACE-PCR verification, revealed seven novel exons in the MB gene
      region, most of which are untranslated exons located 5'-upstream of the coding
      DNA sequence (CDS). Sixteen novel alternatively spliced MB transcripts were
      detected, most of which predominantly occur in tumor tissue or cell lines.
      Quantitative RT-PCR analyses of MB expression in surgical breast cancer specimen
      confirmed the preferential usage of a hitherto unknown, tumor-associated MB
      promoter, which was functionally validated by luciferase reporter gene assays. In
      line with clinical observations of MB up-regulation in avascular breast tumors,
      the novel cancer-associated MB splice variants exhibited increased expression in
      tumor cells subjected to experimental hypoxia. The novel gene regulatory
      mechanisms unveiled in this study support the idea of a non-canonical role of MB
      during carcinogenesis.

PMID- 24026679
TI  - BSCL2/seipin regulates adipogenesis through actin cytoskeleton remodelling.
AB  - Seipin regulates lipid homeostasis by preventing lipid droplet (LD) formation in
      non-adipocytes but promoting it in developing adipocytes. Here, we report that
      seipin interacts with 14-3-3beta through its N- and C-termini. Expression of 14-3
      3beta is upregulated during adipogenesis, and its deletion results in defective
      adipogenesis without affecting key adipogenic transcription factors. We further
      identified the actin-severing protein cofilin-1 as an interacting partner to 14-3
      3beta. Cofilin-1 was spatiotemporally recruited by 14-3-3beta in the cytoplasm
      during adipocyte differentiation. Extensive actin cytoskeleton remodelling, from
      stress fibres to cortical structures, was apparent during adipogenesis, but not
      under lipogenic conditions, indicating that actin cytoskeleton remodelling is
      only required for adipocyte development. Similar to seipin and 14-3-3beta,
      cofilin-1 knockdown led to impaired adipocyte development. At the cellular level,
      differentiated cells with knockdown of cofilin-1, 14-3-3beta or seipin continued
      to maintain relatively intact stress fibres, in contrast to cortical actin
      structure in control cells. Finally, 3T3-L1 cells expressing a severing-resistant
      actin mutant exhibited impaired adipogenesis. We propose that seipin regulates
      adipogenesis by recruiting cofilin-1 to remodel actin cytoskeleton through the 14
      3-3beta protein.

PMID- 24026682
TI  - "Getting blood from a stone": ultrasensitive forensic DNA profiling of
      microscopic bio-particles recovered from "touch DNA" evidence.
AB  - In forensic casework analysis it is sometimes necessary to obtain genetic
      profiles from increasingly smaller amounts of biological material left behind by
      persons involved in criminal offenses. The ability to obtain profiles from trace
      biological evidence is routinely demonstrated with the so-called touch DNA
      evidence (generally perceived to be the result of DNA obtained from shed skin
      cells transferred from donor to an object or a person during physical contact).
      The current method of recovery of trace DNA employs cotton swabs or adhesive tape
      to sample an area of interest. While of practical utility, such a "blind
      swabbing" approach will necessarily co-sample cellular material from the
      different individuals whose cells are present on the item, even if the
      individuals' cells are located in geographically distinct locations on the item.
      Thus some of the DNA mixtures encountered in such touch DNA samples are
      artificially created by the swabbing itself. Therefore, a specialized approach
      for the isolation of single or few cells from "touch DNA evidence" is necessary
      in order to improve the analysis and interpretation of profiles recovered from
      these samples. Here, we describe an optimized and efficient removal strategy for
      the collection of cellular microparticles present in "touch DNA" samples, as well
      as enhanced amplification strategies to permit the recovery of short tandem
      repeat profiles of the donor(s) of the recovered microparticles. 

PMID- 24026680
TI  - CHD7 and retinoic acid signaling cooperate to regulate neural stem cell and inner
      ear development in mouse models of CHARGE syndrome.
AB  - CHARGE syndrome is a multiple congenital anomaly disorder that leads to life
      threatening birth defects, such as choanal atresia and cardiac malformations as
      well as multiple sensory impairments, that affect hearing, vision, olfaction and
      balance. CHARGE is caused by heterozygous mutations in CHD7, which encodes an ATP
      dependent chromatin remodeling enzyme. Identification of the mechanisms
      underlying neurological and sensory defects in CHARGE is a first step toward
      developing treatments for CHARGE individuals. Here, we used mouse models of Chd7
      deficiency to explore the function of CHD7 in the development of the
      subventricular zone (SVZ) neural stem cell niche and inner ear, structures that
      are important for olfactory bulb neurogenesis and hearing and balance,
      respectively. We found that loss of Chd7 results in cell-autonomous
      proliferative, neurogenic and self-renewal defects in the perinatal and mature
      mouse SVZ stem cell niche. Modulation of retinoic acid (RA) signaling prevented
      in vivo inner ear and in vitro neural stem cell defects caused by Chd7
      deficiency. Our findings demonstrate critical, cooperative roles for RA and CHD7
      in SVZ neural stem cell function and inner ear development, suggesting that
      altered RA signaling may be an effective method for treating Chd7 deficiency.

PMID- 24026683
TI  - Detecting microRNA in human cancer tissues with fluorescence in situ
      hybridization.
AB  - The technique of nucleic acid in situ hybridization is an effective method for
      identifying the existence and abundance of nucleic acids in tissue sections or
      cytological preparations. Such a method has the advantage of keeping
      morphological relationships intact while identifying changes at the molecular
      level. As a noncoding regulatory RNA, microRNA has been found to intricately
      control many physiological and pathological conditions. We provide here a
      representative fluorescence in situ hybridization protocol for microRNA
      detection, and note commonly used alternatives, and some troubleshooting points.
      The method described is based on formalin-fixed paraffin-embedded oral cancer
      tissues but should be broadly applicable to similarly processed tissues of other
      types of cancer. 

PMID- 24026681
TI  - A mutation in a ganglioside biosynthetic enzyme, ST3GAL5, results in salt &
      pepper syndrome, a neurocutaneous disorder with altered glycolipid and
      glycoprotein glycosylation.
AB  - 'Salt & Pepper' syndrome is an autosomal recessive condition characterized by
      severe intellectual disability, epilepsy, scoliosis, choreoathetosis, dysmorphic
      facial features and altered dermal pigmentation. High-density SNP array analysis
      performed on siblings first described with this syndrome detected four shared
      regions of loss of heterozygosity (LOH). Whole-exome sequencing narrowed the
      candidate region to chromosome 2p11.2. Sanger sequencing confirmed a homozygous
      c.994G>A transition (p.E332K) in the ST3GAL5 gene, which encodes for a
      sialyltransferase also known as GM3 synthase. A different homozygous mutation of
      this gene has been previously associated with infantile-onset epilepsy syndromes
      in two other cohorts. The ST3GAL5 enzyme synthesizes ganglioside GM3, a
      glycosophingolipid enriched in neural tissue, by adding sialic acid to
      lactosylceramide. Unlike disorders of glycosphingolipid (GSL) degradation, very
      little is known regarding the molecular and pathophysiologic consequences of
      altered GSL biosynthesis. Glycolipid analysis confirmed a complete lack of GM3
      ganglioside in patient fibroblasts, while microarray analysis of
      glycosyltransferase mRNAs detected modestly increased expression of ST3GAL5 and
      greater changes in transcripts encoding enzymes that lie downstream of ST3GAL5
      and in other GSL biosynthetic pathways. Comprehensive glycomic analysis of N
      linked, O-linked and GSL glycans revealed collateral alterations in response to
      loss of complex gangliosides in patient fibroblasts and in zebrafish embryos
      injected with antisense morpholinos that targeted zebrafish st3gal5 expression.
      Morphant zebrafish embryos also exhibited increased apoptotic cell death in
      multiple brain regions, emphasizing the importance of GSL expression in normal
      neural development and function.

PMID- 24026684
TI  - MNAzyme qPCR: a superior tool for multiplex qPCR.
AB  - Multicomponent nucleic acid enzymes (MNAzymes) are nucleic acid enzymes composed
      of multiple oligonucleotide partzymes that only associate to form catalytic
      complexes in the presence of a target nucleic acid. Once assembled, MNAzymes
      cleave a separate substrate (probe) between fluorophore and quencher labels to
      produce a fluorescent signal indicative of the presence of the target. MNAzymes
      are particularly useful as tools for monitoring the accumulation of amplicons
      during real-time quantitative PCR (qPCR). The partzyme pairs have sensor domains
      that are complementary to adjacent regions in the amplicons such that their
      partial catalytic core domains form a complete active MNAzyme core. The probe
      binding domain of the partzymes can be complementary to any one of a series of
      well-characterized universal probes. Since there is no need to synthesize and
      optimize new target-specific probes for each new target, MNAzyme qPCR provides a
      flexible alternative which allows target-specific interrogation with a generic
      readout. A series of universal probes have been designed that perform with high
      reliability, yielding consistent and reproducible results for any target, making
      the development of multiplex qPCR assays faster, cheaper, and simpler. This
      chapter describes a 5plex MNAzyme RT-qPCR method which simultaneously quantifies
      five mRNA transcripts with high efficiency and specificity using five unique
      universal probes, each labeled with a different fluorophore. 

PMID- 24026686
TI  - Detection of SNP-containing human DNA sequences using a split sensor with a
      universal molecular beacon reporter.
AB  - Hybridization-based techniques have been extensively employed for the analysis of
      specific DNA/RNA sequences. Herein, we describe highly specific inexpensive smart
      hybridization-based sensor that takes advantage of a universal molecular beacon
      probe as a fluorescent reporter. The sensor has a straightforward design, and
      demonstrates improved selectivity and specificity of nucleic acid recognition. It
      is cost-efficient since it utilizes the same molecular beacon probe for the
      analysis of many nucleic acid sequences. 

PMID- 24026685
TI  - A new, multiplex, quantitative real-time polymerase chain reaction system for
      nucleic acid detection and quantification.
AB  - Quantitative real-time polymerase chain reaction (qPCR) has emerged as a powerful
      investigative and diagnostic tool with potential to generate accurate and
      reproducible results. qPCR can be designed to fulfil the four key aspects
      required for the detection of nucleic acids: simplicity, speed, sensitivity, and
      specificity. This chapter reports the development of a novel real-time multiplex
      quantitative PCR technology, dubbed PrimRgloTM, with a potential for high-degree
      multiplexing. It combines the capacity to simultaneously detect many viruses,
      bacteria, or nucleic acids, in a single reaction tube, with the ability to
      quantitate viral or bacterial load. The system utilizes oligonucleotide-tagged
      PCR primers, along with complementary fluorophore-labelled and quencher-labelled
      oligonucleotides. The analytic sensitivity of PrimRglo technology was compared
      with the widely used Taqman((r)) and SYBR green detection systems. 

PMID- 24026687
TI  - SNP analysis using a molecular beacon-based operating cooperatively (OC) sensor.
AB  - Analysis of single-nucleotide polymorphisms (SNPs) is important for diagnosis of
      infectious and genetic diseases, for environment and population studies, as well
      as in forensic applications. Herein is a detailed description to design an
      "operating cooperatively" (OC) sensor for highly specific SNP analysis. OC
      sensors use two unmodified DNA adaptor strands and a molecular beacon probe to
      detect a nucleic acid targets with exceptional specificity towards SNPs.
      Genotyping can be accomplished at room temperature in a homogenous assay. The
      approach is easily adaptable for any nucleic acid target, and has been
      successfully used for analysis of targets with complex secondary structures.
      Additionally, OC sensors are an easy-to-design and cost-effective method for SNP
      analysis and nucleic acid detection. 

PMID- 24026688
TI  - Detection of rpoB gene mutations using helicase-dependent amplification.
AB  - For patients infected with tuberculosis, detection of rpoB gene mutations is
      critical for diagnosing drug-resistant strains of the causative pathogen,
      Mycobacterium tuberculosis (MTB). Traditional approaches to drug resistance
      include culture, which is very slow. Recently described real-time polymerase
      chain reaction approaches have addressed turnaround time but at relatively high
      cost. Here, we describe a novel amplification method, termed blocked-primer
      helicase-dependent amplification, for amplifying rpoB gene sequences in MTB.
      Resultant amplicon is hybridized to a probe set arrayed on a modified silicon
      based chip to determine if there is any mutation in that region. Using this
      method, we could detect the majority of clinically relevant mutations in rpoB
      gene. 

PMID- 24026689
TI  - Rapid detection of Brucella spp. using loop-mediated isothermal amplification
      (LAMP).
AB  - Brucella spp. are facultative intracellular bacteria that cause zoonotic disease
      of brucellosis worldwide. Livestock that are most vulnerable to brucellosis
      include cattle, goats, and pigs. Brucella spp. cause serious health problems to
      humans and animals and economic losses to the livestock industry. Traditional
      methods for detection of Brucella spp. take 48-72 h (Kumar et al., J Commun Dis
      29:131-137, 1997; Barrouin-Melo et al., Res Vet Sci 83:340-346, 2007) that do not
      meet the food industry's need of rapid detection. Therefore, there is an urgent
      need of fast, specific, sensitive, and inexpensive method for diagnosing of
      Brucella spp. Loop-mediated isothermal amplification (LAMP) is a method to
      amplify nucleic acid at constant temperatures. Amplification can be detected by
      visual detection, fluorescent stain, turbidity, and electrophoresis. We targeted
      at the Brucella-specific gene omp25 and designed LAMP primers for detection of
      Brucella spp. Amplification of DNA with Bst DNA polymerase can be completed at 65
      degrees C in 60 min. Amplified products can be detected by SYBR Green I stain
      and 2.0% agarose gel electrophoresis. The LAMP method is feasible for detection
      of Brucella spp. from blood and milk samples.

PMID- 24026690
TI  - Loop-mediated isothermal amplification method for a differential identification
      of human Taenia tapeworms.
AB  - Loop-mediated isothermal amplification (LAMP), which employs a Bst DNA polymerase
      with strand-displacement activity and four primers (two inner primers and two
      outer primers) recognizing six distinct regions on the target DNA, is a highly
      sensitive, specific, simple, and rapid nucleotide amplification method. Moreover,
      because the Bst DNA polymerase resists much DNA polymerase inhibitors present in
      biological specimens, the LAMP method is suitable for the detection of infectious
      agents from clinical material such as fecal samples. Here, we describe the LAMP
      method which can differentially detect and identify human Taenia tapeworms,
      Taenia solium, T. saginata, and T. asiatica, using DNA specimens prepared from
      parasite tissue and human fecal sample. 

PMID- 24026692
TI  - DNA detection by cascade enzymatic signal amplification.
AB  - Although many approaches based on template replication were developed and applied
      in DNA detection, cross-contamination from amplicons is always a vexing problem.
      Thus, signal amplification is preferable for DNA detection due to its low risk of
      cross-contamination from amplicons. Here, we proposed a cascade enzymatic signal
      amplification (termed as CESA) by coupling Afu flap endonuclease with nicking
      endonuclease, including three steps: invasive signal amplification, flap
      ligation, and nicking endonuclease signal amplification. Because of the
      advantages of low risk of contamination, no sequence requirement of target DNA,
      and the universal reaction conditions for any target detection, CESA has a great
      potential in clinical diagnosis. 

PMID- 24026691
TI  - Detection of mutation by allele-specific loop-mediated isothermal amplification
      (AS-LAMP).
AB  - For effective control of pathogen-transmitting mosquitoes, precise surveillance
      data of mosquito distribution are essential. Recently, an increase of insecticide
      resistance due to the kdr mutation in Anopheles gambiae, a mosquito that
      transmits the malaria parasite, has been reported. With the aim of developing a
      simple and effective method for surveying resistant mosquitoes, LAMP was applied
      to the allele-specific detection of the kdr gene in An. gambiae. Allele-specific
      LAMP (AS-LAMP) method successfully distinguished the kdr homozygote from the
      heterozygote and the wild type. The robustness of AS-LAMP suggests its usefulness
      for routine identification of insects, not only mosquitoes but also other vectors
      and agricultural pests. Here we describe the method of AS-LAMP to detect mutation
      in Anopheles mosquitoes. 

PMID- 24026693
TI  - Visual DNA detection and SNP genotyping using asymmetric PCR and split DNA
      enzymes.
AB  - We describe a method to detect DNA sequences visually through a color change
      reaction using DNAzymes. We successfully applied the assay for the detection of
      Salmonella and Mycobacterium DNA, as well as for genotyping single base
      differences from within human genomic DNA samples. Our approach adopts a split
      probe targeting system, designed with G-rich sequences, which reassembles in the
      presence of target DNA, producing G-quadruplexes with catalytic activity.
      Asymmetric PCR is first performed to amplify the target region into single
      stranded copies, with primer ratios tailored for optimum amplification. This is
      followed by direct addition of the visual probes, substrates, and reagents to
      produce a color change within 15 min should the desired target sequences be
      present. This approach hence offers a rapid readout, ease-of-use, and handling
      convenience, especially at the point-of-care. 

PMID- 24026694
TI  - Detection of single-stranded nucleic acids via colorimetric means, using G
      quadruplex probes.
AB  - Many molecular biology experiments and clinical diagnostics rely on the detection
      or confirmation of specific nucleic acid sequences. Most DNA or RNA detection
      assays utilize radioactive or fluorescence labeling but although these tags are
      sensitive, safety issues (in the case of radiolabeling) or the need for expensive
      instrumentation (such as a fluorimeter or radiometric detector and the associated
      image analyzer softwares) can sometimes become impediments for some laboratories
      to use these detection tags. G-quadruplexes have emerged as efficient DNA-based
      peroxidases that can convert colorless compounds, such as 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS), into colored products and therefore
      are excellent platforms to use to detect nucleic acids via colorimetric means.
      Here, we describe the detection of a single-stranded DNA template using a split G
      quadruplex probe that is catalytically non-proficient but becomes active after
      being reconstituted upon binding to the target template. 

PMID- 24026695
TI  - Lateral flow biosensors for the detection of nucleic acid.
AB  - The detection of nucleic acid is of central importance for the diagnosis of
      genetic diseases, infectious agents, and biowarfare agents. Traditional
      strategies and technologies for nucleic acid detection are time-consuming and
      labor-intensive. Recently, isothermal strand-displacement reaction-based lateral
      flow biosensors have attracted a great deal of research interest because they are
      sensitive, simple, fast, and easy to use. Here, we describe a lateral flow
      biosensor based on isothermal strand-displacement polymerase reaction and gold
      nanoparticles for the visual detection of nucleic acid. 

PMID- 24026696
TI  - Electrochemiluminescence detection of c-Myc mRNA in breast cancer cells on a
      wireless bipolar electrode.
AB  - Electrochemiluminescence (ECL) on bipolar electrode (BPE) is a sensitive,
      portable, and low-cost approach which has been employed to detect DNA and
      proteins. Here, we develop an ultrasensitive method for intracellular mRNA assay
      based on mRNA-mediated reporter DNA liberation and Ru(bpy)3(2+)-conjugated silica
      nanoparticles (RuSi@Ru(bpy)3(2+)) tag-based signal amplification.

PMID- 24026697
TI  - High-throughput label-free detection of DNA hybridization and mismatch
      discrimination using interferometric reflectance imaging sensor.
AB  - Optical label-free biosensors have demonstrated advantages over fluorescent-based
      detection methods by allowing accurate quantification while also being capable of
      measuring dynamic bimolecular interactions. A simple, high-throughput, solid
      phase, and label-free technique, interferometric reflectance imaging sensor
      (IRIS), can quantify the mass density of DNA with pg/mm(2) sensitivity by
      measuring the optical path difference. We present the design of the IRIS
      instrument and complementary microarrays that can be used to perform a
      quantitative analysis of DNA microarrays. Finally, we present methods to
      accurately calculate the hybridization efficiency and identify SNPs from dynamic
      measurements, as well as supporting software algorithms needed for robust data
      processing. 

PMID- 24026698
TI  - Graphene-PAMAM dendrimer-gold nanoparticle composite for electrochemical DNA
      hybridization detection.
AB  - Graphene oxide is chemically functionalized using planar structured first
      generation polyamidoamine dendrimer (G1PAMAM) to form graphene core GG1PAMAM. The
      monolayer of GG1PAMAM is anchored on the 3-mercapto propionic acid monolayer pre
      immobilized onto a gold transducer. The GG1PAMAM is decorated using gold
      nanoparticles for the covalent attachment of single-stranded DNA through simple
      gold-thiol chemistry. The single- and double-stranded DNAs are discriminated
      electrochemically in the presence of redox probe K3[Fe(CN)6]. Double-stranded
      specific intercalator methylene blue is used to enhance the lower detection
      limit. The use of linear and planar G1PAMAM along with the graphene core has
      enhanced the detection limit 100 times higher than the G1PAMAM with the
      conventional ethylene core. This chapter presents the details of GG1PAMAM
      preparation and application to DNA sensing by electrochemical methods. 

PMID- 24026699
TI  - Application of PNA openers for fluorescence-based detection of bacterial DNA.
AB  - Peptide nucleic acid (PNA) openers have the unique ability to invade double
      stranded DNA with high efficiency and sequence specificity, making it possible to
      detect short (about 20 bp), single-copy bacterial DNA sequences. PNA openers bind
      to a target signature site on one strand of bacterial DNA, leaving the other
      strand open for hybridization with a circularizable oligonucleotide probe. The
      assembled complex serves as a template for rolling circle amplification. The
      obtained amplicon is decorated with short, single-stranded DNA probes carrying
      fluorophores and detected via fluorescence microscopy. 

PMID- 24026700
TI  - DNA probes for FISH analysis of C-negative regions in human chromosomes.
AB  - Fluorescent in situ hybridization (FISH) is a powerful technology for studying
      the chromosome organization and aberrations as well as for searching the homology
      between chromosomal regions in mammals. Currently, FISH is used as a simple,
      rapid, and reliable technique for analyzing chromosomal rearrangements and
      assigning chromosomal breakpoints in modern diagnosing of chromosomal pathology.
      In addition to cloned DNA fragments, the DNA probes produced by sequence
      independent polymerase chain reaction are widely used in FISH assays. As a rule,
      the DNA probes generated from a genomic or chromosomal DNA by whole genome
      amplification are enriched for repetitive elements and, consequently, efficient
      FISH analysis requires that repetitive DNA hybridization is suppressed. The
      linker-adapter polymerase chain reaction (LA-PCR) using the genomic DNA
      hydrolyzed with HaeIII and RsaI restriction endonucleases allows the repetitive
      DNA fraction in DNA probe to be decreased and gene-rich DNA to be predominantly
      amplified. The protocol described here was proposed for production of the DNA
      probes for enhanced analysis of the C-negative regions in human chromosomes. 

PMID- 24026701
TI  - Quantitative analysis of microRNA in blood serum with protein-facilitated
      affinity capillary electrophoresis.
AB  - MicroRNAs play an important role in gene regulation and disease etiology and are
      blood-based biomarkers of diseases. Here, we describe a protein-facilitated
      affinity capillary electrophoresis (ProFACE) method for ultra-sensitive direct
      miRNA detection as low as 300,000 molecules in 1 mL of blood serum, using single
      stranded DNA binding protein (SSB) and double-stranded RNA binding protein (p19)
      as separation enhancers. This method utilizes either the selective binding of SSB
      to a fluorescent single-stranded DNA/RNA probe or the binding of p19 to miRNA-RNA
      probe duplex. 

PMID- 24026702
TI  - High-throughput functional microRNA profiling using recombinant AAV-based
      microRNA sensor arrays.
AB  - There is a lack of methods for high-throughput functional microRNA (miRNA)
      profiling. In this chapter, we describe a recombinant adeno-associated virus
      based miRNA sensor array (miRNA Asensor array), which is able to profile
      functional miRNAs in cultured cells. The preparation of an miRNA Asensor array
      and its usage are discussed. 

PMID- 24026703
TI  - The use of molecular beacons to detect and quantify microRNA.
AB  - Molecular beacons are oligonucleotide (DNA or RNA) probes that have become
      increasingly important tools for RNA sensitive detection both in vitro and in
      living cells. From their inception, molecular beacons have been used to determine
      the expression levels of RNA transcripts, but they also have the specificity to
      identify splice variants and single-nucleotide polymorphisms. Our group has
      performed extensive studies on molecular beacon design, molecular beacon
      hybridization assays, and cellular imaging of mRNA molecules. Compared to other
      methods for assessing RNA transcript expression, such as qRT-PCR, the beacon
      based approach is potentially simpler, faster, more cost effective, and more
      specific. Recently, our group demonstrated that molecular beacons can readily
      distinguish mature- and precursor microRNAs, and reliably quantify microRNA
      expression. MicroRNAs (miRNAs) are a class of short (19-25 nt), single-stranded,
      noncoding RNAs that regulate an array of cellular functions through the
      degradation and translational repression of mRNA targets. Importantly, tissue
      levels of specific miRNAs have been shown to correlate with pathological
      development of diseases. Thus, a rapid and efficient method of assessing miRNA
      expression is useful for diagnosing diseases and identifying novel therapeutic
      targets. Here, we describe the methods for designing and using molecular beacons
      to detect and quantify miRNA.

PMID- 24026704
TI  - Sequence-specific imaging of influenza A mRNA in living infected cells using
      fluorescent FIT-PNA.
AB  - Significant efforts have been devoted to the development of techniques allowing
      the investigation of viral mRNA progression during the replication cycle. We
      herein describe the use of sequence-specific FIT-PNA (Forced Intercalation
      Peptide Nucleic Acids) probes which contain a single intercalator serving as an
      artificial fluorescent nucleobase. FIT-PNA probes are not degraded by enzymes,
      neither by nucleases nor by proteases, and provide for both high sensitivity and
      high target specificity under physiological conditions inside the infected living
      host cell. 

PMID- 24026705
TI  - Application of caged fluorescent nucleotides to live-cell RNA imaging.
AB  - A caged fluorescent nucleic acid probe, which contains a nucleotide modified with
      one photolabile nitrobenzyl unit and two hybridization-sensitive thiazole orange
      units, has been synthesized for area-specific fluorescence imaging of RNA in a
      cell. The probe emits very weak fluorescence regardless of the presence of the
      complementary RNA, whereas it shows hybridization-sensitive fluorescence emission
      after photoirradiation for uncaging. Such probes are generated via several
      chemical synthetic steps and are applicable to area-specific RNA imaging in a
      cell. Only probes that exist in the defined irradiation area are activated via
      uncaging irradiation. 

PMID- 24026706
TI  - The relationship between vagal nerve activity and clinical outcomes in prostate
      and non-small cell lung cancer patients.
AB  - Recent studies suggest that vagal nerve activity, indexed by heart rate
      variability (HRV), could have a prognostic role in cancer. However, most studies
      did not control adequately for confounders and included cardiac patients.
      Furthermore, the validity of this prognostic role needs to be tested in different
      types of cancer. The present study tested the prognostic role of HRV in prostate
      cancer (PC) and non-small cell lung cancer (NSCLC) patients, using a historical
      prospective design. HRV was derived from brief 10 sec ECGs obtained at
      approximately the time of diagnosis in 113 PC patients and 133 NSCLC patients.
      Outcomes included prostate-specific antigen (PSA) at 6 and 24 months in PC, and
      overall survival (OS) (for the full sample) and survival time (for the deceased
      patients) in NSCLC. Furthermore, the possible mediating role of C-reactive
      protein (CRP) was tested (in NSCLC), as well as whether age and stage moderated
      the relationship between HRV and prognosis in both types of cancer. In the PC
      patients, HRV significantly inversely predicted PSA levels at 6 and 24 months,
      independent of confounders. Furthermore, this was particularly significant in
      metastatic PC patients, indicating moderation by stage. In NSCLC patients, HRV
      did not predict OS and survival time, but it did positively predict survival time
      in patients under the age of 65, independent of confounders. Additionally, CRP
      was not found to mediate the relationship between HRV and OS or survival time in
      NSCLC. The present results partly support previous studies and extend them to two
      additional common types of cancer, using a more rigorous control over
      confounders. Together with recent experimental findings, these results propose a
      modulatory role of vagal nerve activity in cancer. Therefore, routine measurement
      of HRV in estimating prognosis in cancer may be considered. 

PMID- 24026707
TI  - Discrete and polymeric heteronuclear constructs derived from triangular 2,2'
      bipyrazine complexes of cis-a2Pt(II) (with a = NH3 or a2 = en).
AB  - cis-[Pta2(H2O)2](2+) (with a = NH3 or a2 = en) and 2,2'-bipyrazine (2,2'-bpz)
      react in water preferentially to cyclic, triangular complexes of composition
      [{cis-Pta2(2,2'-bpz-N4,N4')}3](6+) (a = NH3, 1a; a2 = en, 1b). In their C3
      symmetric conformation (all bridging pyrazine rings adopt cisoid orientations
      with respect to the central C2-C2' bond), 1a and 1b provide three pairs of N1,N1'
      donor sites each, which are capable of chelating additional (hetero)metal ions.
      The latter can in turn bridge to other N1,N1' sites in an intermolecular fashion
      or simply complete their coordination spheres with other ligands (water, anions).
      Four previously not observed structural variants of heteronuclear (Pt(II),
      Cu(II); Pt(II), Ag(I); Pt(II), Cd(II)) constructs have now been isolated by us
      and are reported here: a decanuclear Pt6Cu4 complex, [{(en)Pt(2,2'
      bpz)}3]2Cu4(H2O)6(NO3)20.11H2O (2) with the appearance of a paddle-wheel, a
      dodecanuclear Pt6Cu6 capsule with a Cu(2+) ion in its interior and additional
      Cu(2+) ions in its periphery giving a total composition of [{(en)Pt(2,2'
      bpz)}3]2Cu11(NO3)34(H2O)18.3H2O (3), as well as two coordination polymers,
      {[{(en)Pt(2,2'-bpz)}3]Cd2(H2O)7}(SO4)5.{[Cd(H2O)6](SO4)}.15H2O (4) and [{cis
      (NH3)2Pt(2,2'-bpz)}3]Ag(SiF6)3(BF4).7H2O (5). The structures of these four
      compounds are dominated by host-guest interactions between the triangular metal
      vases of 1a and 1b and anions, respectively, as well as hydrogen bonding
      involving anions and water molecules and electrostatics. In aqueous solution
      considerable dissociation of the heteronuclear compounds 2-5 into the triangular
      Pt complexes 1 and the heterometal ions takes place. Preliminary AFM (atomic
      force microscopy) studies reveal that the +6 cations of 1a have a strong tendency
      to interact with double-stranded DNA with formation of condensed DNA states. 

PMID- 24026708
TI  - On- or off-pump coronary artery bypass grafting: how are you trending?

PMID- 24026709
TI  - Long-term impact of perfusion CT data after subarachnoid hemorrhage.
AB  - INTRODUCTION: Dynamic perfusion computed tomography (PCT) has been established as
      a diagnostic instrument for the detection of vasospasm after subarachnoid
      hemorrhage (SAH). The purpose of this study was to assess the prognostic impact
      of PCT parameters after SAH on the long-term outcome of patients. METHODS: Three
      hundred twelve patients were retrospectively interrogated with a questionnaire
      23.06 +/- 14.33 months after spontaneous subarachnoid hemorrhage. The modified
      Rankin scale (mRS) was determined, respectively. Scheduled PCT data sets from the
      first days after ictus were available for all patients. RESULTS: The maximum mean
      transit time over several examinations per hemisphere (MTTPEAK) values were
      significantly correlated (p <= 0.001, r = 0.422) with the clinical long-term
      outcome (mRS). Corresponding to our linear regression analysis, MTTPEAK is the
      second most important regressor (behind clinical severity of the initial
      hemorrhage) for the prediction of long-term mRS. An MTTPEAK threshold of 3.98 s
      (identified by receiver operating characteristic analysis, area under the curve =
      0.75) predicted an unfavorable long-term outcome (mRS >= 2) with a sensitivity,
      specificity, positive predictive value, negative predictive value, and diagnostic
      accuracy of 67.3, 74.3, 84.5, 52.1, and 69.6 %, respectively. CONCLUSION: The
      presented data corroborate the relevance of PCT data for the clinical long-term
      outcome of SAH patients. By identification of patients who are at risk for a bad
      outcome and may need escalation of therapy, risk-benefit analysis is supported.

PMID- 24026710
TI  - Atrial fibrillation ablation in octogenarians: where do we stand?
AB  - The prevalence of atrial fibrillation increases significantly with age, affecting
      nearly 10 % of adults greater than 80 years of age. Complications from atrial
      fibrillation, including stroke, also increase with age. Medical therapy includes
      anticoagulation, ventricular rate control, and if symptoms persist, maintenance
      of sinus rhythm with antiarrhythmic drugs. However, anticoagulation and
      antiarrhythmic therapy is often challenging in the elderly due to side effects,
      comorbidities, and heightened sensitivity to medications. Catheter based ablation
      of atrial fibrillation is an effective treatment for paroxysmal atrial
      fibrillation. However, the major randomized controlled trials, such as Thermocool
      AF and STOP-AF studies, have excluded the elderly patients. Current guidelines
      suggest caution when considering ablation for elderly patients due to a lack of
      available data. We will review recent studies that have observed the outcomes of
      atrial fibrillation ablation in the elderly, specifically those studies that
      included octogenarians.

PMID- 24026711
TI  - Post-treatment lyme syndrome and central sensitization.
AB  - Central sensitization is a process that links a variety of chronic pain disorders
      that are characterized by hypersensitivity to noxious stimuli and pain in
      response to non-noxious stimuli. Among these disorders, treatments that act
      centrally may have greater efficacy than treatments acting peripherally. Because
      many individuals with post-treatment Lyme syndrome (PTLS) have a similar symptom
      cluster, central sensitization may be a process mediating or exacerbating their
      sensory processing. This article reviews central sensitization, reports new data
      on sensory hyperarousal in PTLS, explores the potential role of central
      sensitization in symptom chronicity, and suggests new directions for
      neurophysiologic and treatment research. 

PMID- 24026712
TI  - Psychiatric disorders in children and adolescents in the first six months after
      mild traumatic brain injury.
AB  - The objective was to assess the nature, rate, predictive factors, and
      neurocognitive correlates of novel psychiatric disorders (NPD) after mild
      traumatic brain injury (MTBI). Children age 5-14 years with MTBI (N=87) from
      consecutive admissions to five trauma centers were enrolled and studied with
      semistructured psychiatric interviews soon after injury (baseline), and 70 of
      these children were assessed again 6 months post-injury. Injury severity; lesion
      characteristics; pre-injury variables, including psychiatric disorder, family
      psychiatric history, family functioning, socioeconomic status, psychosocial
      adversity, and adaptive functioning; and post-injury neurocognitive and adaptive
      functioning measures were assessed with standardized instruments. NPD occurred in
      25 of 70 participants (36%) in the first 6 months after injury. NPD at 6 months
      was predicted by the presence of frontal white-matter lesions on MRI at 3 months
      post-injury, and was associated with concurrent decrements on neurocognitive
      indices of processing speed, expressive language, and intellectual functioning.
      NPD was not predicted by other indices of severity, pre-injury psychosocial
      variables, estimated pre-injury academic functioning, or adaptive and executive
      function decrements 6 months post-injury. These findings suggest that short-term
      psychiatric morbidity associated with MTBI in children and adolescents may be
      more common than previously thought and may have readily identifiable
      neuroimaging and neurocognitive correlates. 

PMID- 24026713
TI  - Depression, anxiety, and disturbed sleep in glaucoma.
AB  - Although it has been suggested that glaucoma is associated with circadian
      misalignment, sleep disorder, anxiety, and depression, these comorbid conditions
      have not received much attention. This study provides evidence for a
      significantly higher prevalence of depression, trait anxiety, and sleep
      disturbances in patients with progressed glaucoma, as compared with glaucoma
      patients with no or minor visual field defects (VFD). Logistic-regression
      analyses suggest that severe VFD constitute a significant predictor of
      depression, trait-anxiety, and sleep disturbance. Results indicate the necessity
      of regular screening and psychochronobiological treatment in glaucoma patients. 

PMID- 24026714
TI  - White-matter connectivity and methylphenidate-induced changes in attentional
      performance according to alpha2A-adrenergic receptor gene polymorphisms in Korean
      children with attention-deficit hyperactivity disorder.
AB  - The authors examined the association between the MspI C/G and DraI C/T genotypes
      of the alpha2A-adrenergic receptor gene and white-matter connectivity and
      attentional performance before and after medication in 53 children with attention
      deficit hyperactivity disorder. Subjects who carried the T allele at the DraI
      polymorphism showed fewer changes in the mean commission error scores after 8
      weeks of medication and decreased fractional anisotropy (FA) values in the right
      middle frontal cortex than subjects without the T allele. Subjects with the C
      allele at the MspI polymorphism showed decreased FA values in the right
      postcentral gyrus than subjects without. 

PMID- 24026715
TI  - Aggression, impulsivity, and psychopathic traits in combined antisocial
      personality disorder and substance use disorder.
AB  - Aggression, impulsivity, and psychopathic traits are prominent in both antisocial
      personality disorder (ASPD) and substance use disorders (SUD), but have rarely
      been examined collectively. The authors' results show that all three variables
      were elevated in adults with comorbid ASPD/SUD, relative to SUD-only and control
      subjects. 

PMID- 24026716
TI  - The correlation between impaired attention and emotional reactivity in depressed
      adolescent patients.
AB  - A group of 20 drug-naive depressed adolescents and 20 matched controls underwent
      cognitive evaluations and assessment of emotional reactivity. Emotional
      reactivity correlated only with attention and only in depressed patients. The
      cognitive-emotional construct may enhance the understanding of adolescent
      depression and aid diagnosis. 

PMID- 24026717
TI  - Disorders of consciousness and N400 ERP measures in response to a semantic task.
AB  - Disorders of consciousness (DOC) have been studied in recent years. In the
      present research, electrophysiological measures (ERPs) were used to verify the
      preservation of semantic linguistic processes in vegetative states (VS) and
      minimal-consciousness state (MCS). Eighteen patients classified as VS or MCS, and
      20 controls were submitted to a semantic associative task with congruous or
      incongruous word sequences (auditory stimuli). An increased N400 peak amplitude
      within the fronto-central cortical areas was shown in response to incongruous
      sequences for both patients and controls. Thus, semantic processing was partially
      preserved in both VS and MCS patients. 

PMID- 24026721
TI  - Colloid cyst presenting as recurrent mania.

PMID- 24026722
TI  - A case of Dandy-Walker variant disorder associated with multiple neuropsychiatric
      comorbidities managed with behavioral therapy.

PMID- 24026723
TI  - Patient With voltage-gated potassium-channel (VGKC) limbic encephalitis found to
      have Creutzfeldt-Jakob disease (CJD) at autopsy.

PMID- 24026724
TI  - Punding as a transient symptom in a patient with an early-onset form of dementia.

PMID- 24026725
TI  - A suicide attempt in a context of bipolar symptoms leading to a diagnosis of
      Sneddon syndrome.

PMID- 24026726
TI  - Treatment of catatonia with zolpidem.

PMID- 24026727
TI  - Othello syndrome in a patient with right orbitofrontal lobe cavernous sinus
      hemorrhage.

PMID- 24026728
TI  - Reduplicative paramnesia: not only one.

PMID- 24026729
TI  - Transience of dysexecutive syndrome but permanence of motor deficits in the
      course of recurrent subfrontal meningioma.

PMID- 24026730
TI  - Bipolar I disorder presaging X-linked adrenoleukodystrophy.

PMID- 24026731
TI  - Psychiatric disturbance and mild intellectual disability in the context of a
      vascular malformation (capillary telangiectasia) of the posterior hippocampus and
      subiculum.

PMID- 24026732
TI  - Donepezil-induced confusional state in a patient with autopsy-proven behavioral
      variant frontotemporal dementia.

PMID- 24026733
TI  - Tardive dyskinesia associated with anastrozole.

PMID- 24026734
TI  - Successful treatment with blonanserin for drug-induced hyperprolactinemia in
      chronic schizophrenia patients: a six-month follow-up of two cases.

PMID- 24026736
TI  - Experience with intramuscular zuclopenthixol and medroxyprogesterone acetate in
      the treatment of agitation and aggression in Huntington's disease.

PMID- 24026735
TI  - Increased sensitivity to atypical antipsychotics in a patient with Dandy-Walker
      variant with schizophrenia.

PMID- 24026737
TI  - Munchausen's syndrome with rare hematological disorder, systemic mastocytosis: a
      case report.

PMID- 24026738
TI  - Adjunctive yokukansan treatment improved cognitive functions in a patient with
      schizophrenia.

PMID- 24026739
TI  - Patient with globus pallidus infarction presenting with reversible dementia.

PMID- 24026740
TI  - Reduction in Parkinson's disease therapy improved punding but not feeling of
      presence.

PMID- 24026741
TI  - Cerebellar cognitive affective syndrome in Dandy-Walker variant disorder.

PMID- 24026742
TI  - Immediate response to lorazepam in a patient with 17 years of chronic catatonia.

PMID- 24026743
TI  - A possible case of transient Anton's Syndrome status post bilateral occipital
      lobe infarct.

PMID- 24026744
TI  - Clozapine-induced recurrent pulmonary thromboembolism.

PMID- 24026745
TI  - Soft-tissue manipulation contributes to craniofacial symmetry as importantly as
      does implant reconstruction in cranioplasty for skull defects.

PMID- 24026746
TI  - Low-dose quetiapine for the treatment of delusional disorder in a patient with
      Von Hippel-Lindau disease.

PMID- 24026747
TI  - Loss of emotional responsiveness secondary to left amygdalohippocampectomy
      performed for the treatment of complex, drug-resistant partial epilepsy.

PMID- 24026748
TI  - Using brain network graph modeling to explore the cause of non-motor symptoms in
      Parkinson's disease.

PMID- 24026749
TI  - Quetiapine of non-suicidal self-injury associated with dysphoric mania and
      ultradian cycling bipolar disorder.

PMID- 24026750
TI  - The importance of thalamic connections: cognition, arousal, and behavior in
      thalamic stroke.

PMID- 24026751
TI  - Neuroanatomical abnormalities before the onset of various types of delusions in a
      patient with Alzheimer disease.

PMID- 24026752
TI  - Psychotic disorder due to neurosyphilis.

PMID- 24026753
TI  - Valproate-induced hyperammonemic encephalopathy followed by benzodiazepine
      withdrawal in a patient with schizoaffective disorder: a differential diagnosis.

PMID- 24026754
TI  - A look inside the mirror neuron system.

PMID- 24026755
TI  - Theoretical analysis and quantification of the absorption spectra of uranyl
      complexes with structurally-related tridentate ligands.
AB  - A semi-empirical model of vibronic coupling was developed in the present work to
      provide a quantitative analysis of partially resolved vibronic structure in
      uranyl absorption spectra. The studied uranyl complexes share a similar structure
      but bear different electric charges in the equatorial ligands. Their optical
      absorption spectra exhibit the common characteristics of charge transfer vibronic
      transitions of uranyl complexes but fine structures arising from specific
      vibrational modes are obscured. Accordingly, in application of the Franck-Condon
      principle of vibronic coupling, our model takes a mode-degenerate approximation.
      The absorption spectra of uranyl in various ligand environments were calculated
      and fitted to the experimental data. The semi-empirical approach enabled
      quantitative evaluation of the electronic energy levels, vibrational frequencies,
      and vibronic coupling strength. Moreover, the expansion of the U=O bond in the
      excited states was calculated from the values of the vibronic coupling parameters
      determined in simulation of the experimental spectra. The calculated results
      agree very well with the experimentally observed trends in thermodynamic binding
      constants and structural parameters. A theoretical interpretation is given to the
      dependence of the U=O bond expansion on the charges carried by the uranyl ligand
      complexes.

PMID- 24026756
TI  - [Operative treatment strategies for multiple trauma patients : early total care
      versus damage control].
AB  - The treatment of multiple trauma patients is a great challenge for an
      interdisciplinary team. After preclinical care and subsequent treatment in the
      emergency room the order of the interventions is prioritized depending of the
      individual risk stratification. For planning the surgery management it is
      essential to distinguish between absolutely essential operations to prevent life
      threatening situations for the patient and interventions with shiftable
      indications, depending on the general condition of the patient. All interventions
      need to be done without causing significant secondary damage to prohibit
      hyperinflammation and systemic inflammatory response syndrome. The challenge
      consists in determination of the appropriate treatment at the right point in
      time. In general the early primary intervention, early total care, is
      differentiated from the damage control concept. 

PMID- 24026759
TI  - Determining anaerobic capacity in sporting activities.
AB  - Anaerobic capacity/anaerobically attributable power is an important parameter for
      athletic performance, not only for short high-intensity activities but also for
      breakaway efforts and end spurts during endurance events. Unlike aerobic
      capacity, anaerobic capacity cannot be easily quantified. The 3 most commonly
      used methodologies to quantify anaerobic capacity are the maximal accumulated
      oxygen deficit method, the critical power concept, and the gross efficiency
      method. This review describes these methods, evaluates if they result in similar
      estimates of anaerobic capacity, and highlights how anaerobic capacity is used
      during sporting activities. All 3 methods have their own strengths and weaknesses
      and result in more or less similar estimates of anaerobic capacity but cannot be
      used interchangeably. The method of choice depends on the research question or
      practical goal. 

PMID- 24026758
TI  - Cardiovascular changes during chronic hypertensive states.
AB  - It is well established that elevated blood pressure constitutes a major risk
      factor for coronary heart disease, arrythmias, heart failure, cerebrovascular
      disease, peripheral artery disease and renal failure. Blood pressure level and
      the duration of arterial hypertension (HTN) impact target organ damage. Many
      studies in adults have demonstrated the role of antihypertensive therapy in
      preventing cardiovascular (CV) events. The so-called hard end-points, such as
      death, myocardial infarction (MI) or stroke, are rarely seen in children, but
      intermediate target organ damage, including left ventricular hypertrophy,
      increased intima-media thickness and microalbuminuria, is already detectable
      during childhood. The goal of antihypertensive treatment is to reduce the global
      risk of CV events. In the adult population stratification of CV risk is based on
      blood pressure level, risk factors, subclinical target organ damage and
      established CV and kidney disease. Increased CV risk begins early in the course
      of kidney disease, and CV diseases are the most frequent cause of morbidity and
      mortality in patients with chronic kidney disease (CKD). Children with CKD are
      especially prone to the long-term effects of CV risk factors, which result in
      high morbidity and mortality in young adults. To improve the outcome, pediatric
      and adult CKD patients require nephro- and cardioprotection. 

PMID- 24026768
TI  - Roles of adiponectin and oxidative stress in obesity-associated metabolic and
      cardiovascular diseases.
AB  - The recent increase in populations with obesity is a worldwide social problem,
      and the enhanced susceptibility of obese people to metabolic and cardiovascular
      diseases has become a growing health threat. An understanding of the molecular
      basis for obesity-associated disease development is required to prevent these
      diseases. Many studies have revealed that the mechanism involves various
      bioactive molecules that are released from adipose tissues and designated as
      adipocytokines/adipokines. Adiponectin is an adipocytokine that exerts insulin
      sensitizing effects in the liver and skeletal muscle via adenosine monophosphate
      activated protein kinase and proliferator-activated receptor alpha activation.
      Additionally, adiponectin can suppress atherosclerosis development in vascular
      walls via various anti-inflammatory effects. In contrast, oxidative stress is a
      harmful factor that systemically increases during obesity and promotes the
      development of diabetes, atherosclerosis, and various other diseases. In obese
      mice, oxidative stress is enhanced in adipose tissue before diabetes development,
      but not in the liver, skeletal muscle, and aorta, suggesting that in obesity,
      adipose tissue may be a major source of reactive oxygen species (ROS). ROS
      suppress adiponectin production in adipocytes. Treatment of obese mice with anti
      oxidative agents improves insulin resistance and restores adiponectin production.
      Recent studies have demonstrated that adiponectin protects against oxidative
      stress-induced damage in the vascular endothelium and myocardium. Thus, decreased
      circulating adiponectin levels and increased oxidative stress, which are closely
      linked to each other, should be deeply involved in obesity-associated metabolic
      and cardiovascular disease pathogenesis. 

PMID- 24026757
TI  - Recreating kidney progenitors from pluripotent cells.
AB  - Access to human pluripotent cells theoretically provides a renewable source of
      cells that can give rise to any required cell type for use in cellular therapy or
      bioengineering. However, successfully directing this differentiation remains
      challenging for most desired endpoints cell type, including renal cells. This
      challenge is compounded by the difficulty in identifying the required cell type
      in vitro and the multitude of renal cell types required to build a kidney. Here
      we review our understanding of how the embryo goes about specifying the cells of
      the kidney and the progress to date in adapting this knowledge for the recreation
      of nephron progenitors and their mature derivatives from pluripotent cells. 

PMID- 24026769
TI  - Homologue gene of bile acid transporters ntcp, asbt, and ost-alpha in rainbow
      trout Oncorhynchus mykiss: tissue expression, effect of fasting, and response to
      bile acid administration.
AB  - Bile acid transporters belonging to the SLC10A protein family, Na+ taurocholate
      cotransporting polypeptide (NTCP or SLC10A1), apical sodium-dependent bile salt
      transporter (ASBT or SLC10A2), and organic solute transporter alpha (Ost-alpha)
      have been known to play critical roles in the enterohepatic circulation of bile
      acids in mammals. In this study, ntcp, asbt, and ost-alpha-1/-2 cDNA were cloned,
      their tissue distributions were characterized, and the effects of fasting and
      bile acid administration on their expression were examined in rainbow trout
      Oncorhynchus mykiss. The structural characteristics of Ntcp, Asbt, and Ost-alpha
      were well conserved in trout, and three-dimensional structure analysis showed
      that Ntcp and Asbt were similar to each other. Tissue distribution analysis
      revealed that trout asbt was primarily expressed in the hindgut, while ntcp
      expression occurred in the brain, and ost-alpha-1/-2 was mainly expressed in the
      liver or ovary. Although asbt and ost-alpha-1 mRNA levels in the gut increased in
      response to fasting for 4 days, ost-alpha-1 expression in the liver decreased.
      Similarly, bile acid administration increased asbt and ost-alpha-1 expression
      levels in the gut, while those of ntcp and ost-alpha-2 in the liver decreased.
      These results suggested that the genes asbt, ntcp, and ost-alpha are involved in
      bile acid transport in rainbow trout.

PMID- 24026770
TI  - Production of AI-2 is mediated by the S-ribosylhomocystein lyase gene luxS in
      Bacteroides fragilis and Bacteroides vulgatus.
AB  - Quorum sensing is a cell-cell signaling mechanism based on cell density and that
      involves the production of hormone-like molecules called autoinducers (AI). One
      of the most studied AIs has been termed AI-2, and its biosynthesis requires the
      enzyme encoded by luxS. We have previously described for the first time that
      Bacteroides species can produce molecules with AI-2 activity. In this study, we
      focus on the detection of luxS and its activity as the AI-2 synthase in
      Bacteroides species. The strains Bacteroides fragilis B3b and Bacteroides
      vulgatus ATCC 8482 were selected based on a positive phenotype for AI-2
      production and the presence of a putative luxS in the genome, respectively. In
      order to identify the luxS gene, cloning and heterologous expression strategies
      were utilized. We demonstrate that both strains contain functional luxS orthologs
      that can complement AI-2 production in Escherichia coli.

PMID- 24026772
TI  - Age-specific Mycoplasma pneumoniae pneumonia-associated myocardial damage in
      children.
AB  - OBJECTIVE: To measure Mycoplasma pneumoniae pneumonia (MPP)-associated myocardial
      damage in different age groups of children with pneumonia. METHODS: Children aged
      0-14 years with pneumonia and myocardial damage (serum creatine kinase isoenzyme
      MB [CK-MB] concentration >25 U/l) were enrolled in the study. The children were
      classified as Mycoplasma pneumoniae immunoglobulin M positive (M. pneumoniae
      IgM+) or negative (M. pneumoniae IgM-) based on a serological test. Children were
      stratified into four age groups in order to analyse age-specific MPP-associated
      myocardial damage. RESULTS: The incidence of fever was significantly higher in
      children who were M. pneumoniae IgM+ compared with M. pneumoniae IgM- children.
      The median serum CK-MB concentration was significantly higher in children who
      were M. pneumoniae IgM+ compared with those who were M. pneumoniae IgM-. Children
      who were M. pneumoniae IgM+ in the 13-36 months and 72 months-14 years age groups
      had significantly higher median serum CK-MB concentrations than those who were M.
      pneumoniae IgM- in the same age group. CONCLUSIONS: M. pneumoniae infection was
      associated with greater myocardial damage in children aged 13-36 months and 72
      months-14 years. This suggests age-specific immune responses to M. pneumoniae.

PMID- 24026773
TI  - Altered brain connectivity in patients with psychogenic non-epileptic seizures: a
      scalp electroencephalography study.
AB  - OBJECTIVE: To determine the role of altered brain connectivity in patients with
      psychogenic non-epileptic seizures (PNES). METHODS: Patients with PNES and age-
      and sex-matched healthy control subjects were enrolled. Participants underwent
      neuropsychological evaluation (anxiety, depression and dissociation) and
      interictal scalp electroencephalography (EEG). A brain network was constructed.
      Between-group differences in clustering coefficient and global efficiency were
      analysed. RESULTS: Patients with PNES (n = 15) had significantly decreased
      clustering coefficients in the gamma band compared with controls (n = 15).
      Difference topology revealed that patients with PNES had decreased long linkage
      between the frontal region and other regions compared with controls. There were
      no significant between-group differences in global efficiency. Neuropsychological
      scores were significantly higher in patients than controls, but there were no
      correlations with network properties. CONCLUSION: Altered brain connectivity in
      patients with PNES suggests an underlying pathophysiological mechanism. EEG and
      network analysis allow noninvasive exploration of the neurological processes of
      this disease.

PMID- 24026771
TI  - Mmp-9 inhibition: a therapeutic strategy in ischemic stroke.
AB  - Ischemic stroke is a leading cause of disability worldwide. In cerebral ischemia
      there is an enhanced expression of matrix metallo-proteinase-9 (MMP-9), which has
      been associated with various complications including excitotoxicity, neuronal
      damage, apoptosis, blood-brain barrier (BBB) opening leading to cerebral edema,
      and hemorrhagic transformation. Moreover, the tissue plasminogen activator (tPA),
      which is the only US-FDA approved treatment of ischemic stroke, has a brief 3 to
      4 h time window and it has been proposed that detrimental effects of tPA beyond
      the 3 h since the onset of stroke are derived from its ability to activate MMP-9
      that in turn contributes to the breakdown of BBB. Therefore, the available
      literature suggests that MMP-9 inhibition can be of therapeutic importance in
      ischemic stroke. Hence, combination therapies of MMP-9 inhibitor along with tPA
      can be beneficial in ischemic stroke. In this review we will discuss the current
      status of various strategies which have shown neuroprotection and extension of
      thrombolytic window by directly or indirectly inhibiting MMP-9 activity. In the
      introductory part of the review, we briefly provide an overview on ischemic
      stroke, commonly used models of ischemic stroke and a role of MMP-9 in ischemia.
      In next part, the literature is organized as various approaches which have proven
      neuroprotective effects through direct or indirect decrease in MMP-9 activity,
      namely, using biotherapeutics, involving MMP-9 gene inhibition using viral
      vectors; using endogenous inhibitor of MMP-9, repurposing of old drugs such as
      minocycline, new chemical entities like DP-b99, and finally other approaches like
      therapeutic hypothermia. 

PMID- 24026774
TI  - Impaired aortic distensibility in hypothyroid patients with negative coronary
      angiograms: simultaneous evaluation with 128-slice multiple row detector computed
      tomography.
AB  - OBJECTIVE: To determine the relationship between arterial distensibility and
      hypothyroidism by simultaneous assessment of coronary angiography and aortic
      distensibility, measured using 128-slice retrospective electrocardiogram-gated
      multiple row detector computed tomography (MDCT). METHODS: Untreated hypothyroid
      patients and age-matched euthyroid patients, who underwent 128-slice
      retrospective electrocardiogram-gated MDCT to evaluate the coronary arteries,
      were assessed. Intraluminal aortic areas in systolic and diastolic phases of the
      cardiac cycle were measured with multiphase reformation at predefined locations
      including the ascending aorta, proximal descending aorta and distal descending
      aorta in the widest axial plane. RESULTS: The study included 21 hypothyroid and
      21 euthyroid patients. Patients with hypothyroidism exhibited decreased aortic
      distensibility between each location in the thoracic aorta (ascending aorta,
      proximal descending aorta and distal descending aorta) compared with euthryoid
      patients. CONCLUSIONS: Hypothyroidism was associated with preclinical vascular
      alteration, characterized by impaired aortic distensibility at each location of
      the thoracic aorta, which has been shown to be related to increased
      cardiovascular risk. Monitoring of aortic distensibility is relevant for
      evaluating coronary artery disease progression and treatment choices.

PMID- 24026775
TI  - Benefits of a frame-based stereotactic surgical planning system for the treatment
      of spontaneous intracerebral haematomas.
AB  - OBJECTIVE: Frame-based stereotactic surgical planning systems (SSPSs) have been
      used for deep brain stimulation and radioneurosurgery. Here, we evaluated the
      feasibility, safety and efficacy of using a SSPS to aid spontaneous intracerebral
      haematoma (ICH) treatment. METHODS: Patients with moderate spontaneous putamen
      haematomas were randomized into two groups: treatment (group A) and control
      (group B). In group B, the catheter for evacuating haematomas was inserted into a
      target point, located at the centre of the haematoma, using conventional frame
      based stereotactics; urokinase thrombolysis was subsequently delivered through
      the catheter. In group A, this procedure was assisted by a SSPS, which designed
      both the target point and trajectory in the haematoma through virtual reality.
      Duration of evacuating haematomas and number of urokinase injections was compared
      between groups. RESULTS: In total, 65 patients were recruited: in group A (n =
      30), the duration of evacuating haematomas (35.27 +/- 9.17 h) was shorter than in
      group B (n = 35; 67.77 +/- 13.82 h). There were fewer urokinase injections in
      group A (3.63 +/- 1.16) than in group B (6.40 +/- 1.29). CONCLUSIONS: The
      feasibility, efficacy and safety of spontaneous ICH treatment were optimized by
      the use of a frame-based SSPS.

PMID- 24026777
TI  - 'There are no facts, only interpretations'.

PMID- 24026776
TI  - Pretreatment of baicalin and wogonoside with glycoside hydrolase: a promising
      approach to enhance anticancer potential.
AB  - Previous phytochemical studies showed that the major flavonoids in Scutellaria
      baicalensis are baicalin, baicalein, wogonoside and wogonin. The two glycosides
      (baicalin and wogonoside) can be transformed into their aglycons (baicalein and
      wogonin), which possess positive anticancer potential. In this study, we used
      glycosidase to catalyze flavonoids in S. baicalensis to enhance the herb's
      anticancer activities. Our HPLC data showed that, using the optimized conditions
      obtained in our experiments (20 U/g of cellulase, 50C, pH 4.8 and treatment for 8
      h), there was a marked transformation from the two glycosides to their aglycons.
      The anticancer activity was subsequently evaluated using a series of S.
      baicalensis extracts in which variable lengths of glycosidase treatment time were
      used. Combining analytical and bioassay results, we observed that the higher the
      aglycon content, the stronger the antiproliferation effects. Compared to the
      untransformed control, 8 h of glycosidase catalyzing significantly increased
      antiproliferative activity on human colorectal and breast cancer cells, and its
      cancer cell growth inhibition is, in part, mediated by cell cycle arrest at the S
      phase and induction of apoptosis. Data from this study suggest that using
      glycosidase to catalyze S. baicalensis offers a promising approach to increase
      its anticancer activity. 

PMID- 24026783
TI  - Coping on canvas.

PMID- 24026780
TI  - Management of burn wounds.
AB  - Small and moderate scalds in toddlers are still the most frequent thermal
      injuries the pediatric surgeons have to face today. Over the last years, surgical
      treatment of these patients has changed in many aspects. Due to new dressing
      materials and new surgical treatment strategies that are particularly suitable
      for children, today, far better functional and aesthetic long-term results are
      possible. While small and moderate thermal injuries can be treated in most
      European pediatric surgical departments, the severely burned child must be
      transferred to a specialized, ideally pediatric, burn center, where a well
      trained multidisciplinary team under the leadership of a (ideally pediatric) burn
      surgeon cares for these highly demanding patients. In future, tissue engineered
      full thickness skin analogues will most likely play an important role, in
      pediatric burn as well as postburn reconstructive surgery. 

PMID- 24026779
TI  - Inflammatory cytokines and risk of coronary heart disease: new prospective study
      and updated meta-analysis.
AB  - AIMS: Because low-grade inflammation may play a role in the pathogenesis of
      coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory
      cascades, this study aimed to assess the associations of several pro-inflammatory
      cytokines and CHD risk in a new prospective study, including meta-analysis of
      prospective studies. METHODS AND RESULTS: Interleukin-6 (IL-6), IL-18, matrix
      metalloproteinase-9 (MMP-9), soluble CD40 ligand (sCD40L), and tumour necrosis
      factor-alpha (TNF-alpha) were measured at baseline in a case-cohort study of 1514
      participants and 833 incident CHD events within population-based prospective
      cohorts at the Danish Research Centre for Prevention and Health. Age- and sex
      adjusted hazard ratios (HRs) for CHD per 1-SD higher log-transformed baseline
      levels were: 1.37 (95% CI: 1.21-1.54) for IL-6, 1.26 (1.11-1.44) for IL-18, 1.30
      (1.16-1.46) for MMP-9, 1.01 (0.89-1.15) for sCD40L, and 1.13 (1.01-1.27) for TNF
      alpha. Multivariable adjustment for conventional vascular risk factors attenuated
      the HRs to: 1.26 (1.08-1.46) for IL-6, 1.12 (0.95-1.31) for IL-18, 1.21 (1.05
      1.39) for MMP-9, 0.93 (0.78-1.11) for sCD40L, and 1.14 (1.00-1.31) for TNF-alpha.
      In meta-analysis of up to 29 population-based prospective studies, adjusted
      relative risks for non-fatal MI or CHD death per 1-SD higher levels were: 1.25
      (1.19-1.32) for IL-6; 1.13 (1.05-1.20) for IL-18; 1.07 (0.97-1.19) for MMP-9;
      1.07 (0.95-1.21) for sCD40L; and 1.17 (1.09-1.25) for TNF-alpha. CONCLUSIONS:
      Several different pro-inflammatory cytokines are each associated with CHD risk
      independent of conventional risk factors and in an approximately log-linear
      manner. The findings lend support to the inflammation hypothesis in vascular
      disease, but further studies are needed to assess causality.

PMID- 24026778
TI  - Impact of intracoronary bone marrow cell therapy on left ventricular function in
      the setting of ST-segment elevation myocardial infarction: a collaborative meta
      analysis.
AB  - AIMS: The objective of the present analysis was to systematically examine the
      effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV)
      function after ST-segment elevation myocardial infarction in various subgroups of
      patients by performing a collaborative meta-analysis of randomized controlled
      trials. METHODS AND RESULTS: We identified all randomized controlled trials
      comparing intracoronary BMC infusion as treatment for ST-segment elevation
      myocardial infarction. We contacted the principal investigator for each
      participating trial to provide summary data with regard to different pre
      specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous
      coronary intervention, infarct-related artery, LV end-diastolic volume index
      (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular
      obstruction, timing of cell infusion, and injected cell number] and three
      different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index
      (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell
      therapy, 657 controls). The absolute improvement in LVEF was greater among BMC
      treated patients compared with controls: [2.55% increase, 95% confidence interval
      (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI
      (-3.17 mL/m2, 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m2, 95% CI -3.84 to 
      1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement
      was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39)
      compared with older patients (age >= 55 years, 1.77%, 95% CI: 0.80-2.74, P =
      0.03). This heterogeneity in treatment effect was also observed with respect to
      the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40%
      derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%,
      95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to
      2.31 in LVEF >= 40%, P < 0.001. No clear interaction was observed between other
      subgroups and outcomes. CONCLUSION: Intracoronary BMC infusion is associated with
      improvement of LV function and remodelling in patients after ST-segment elevation
      myocardial infarction. Younger patients and patients with a more severely
      depressed LVEF at baseline derived most benefit from this adjunctive therapy.

PMID- 24026784
TI  - Spiny follicular hyperkeratotic papules on the face.

PMID- 24026785
TI  - Questions concerning nasal intermittent positive-pressure ventilation vs nasal
      continuous positive airway pressure.

PMID- 24026787
TI  - Questions concerning nasal intermittent positive-pressure ventilation vs nasal
      continuous positive airway pressure--Reply.

PMID- 24026788
TI  - When your child does not need antibiotics.

PMID- 24026789
TI  - [Diseases in gastroenterology].
AB  - Autoimmune diseases of gastrointestinal organs require a timely diagnosis to
      facilitate appropriate treatment. It is an important challenge to differentiate
      autoimmune pancreatitis (AIP) from pancreatic carcinoma. This is hampered by the
      occurrence of focal changes in the pancreatic parenchyma in AIP. Additionally,
      lymphadenopathy and duct obstruction are present. Autoimmune hepatitis (AIH)
      results in liver cirrhosis and organ failure if not discovered in time. In 40 %
      of patients with AIH the initial diagnosis is not achieved at an early stage.
      Intestinal tuberculosis must be differentiated from Crohn's disease, especially
      if modern biotherapies employing antibodies are planned. 

PMID- 24026790
TI  - [Leg discoloration].
AB  - Many patients present with discolouration of the legs or with non-ulcerating skin
      lesions, the most frequent causes being chronic venous insufficiency or other
      chronic or acute states of congestion. Erysipelas (cellulitis) is also a frequent
      example of a bacterial skin infection. A complex differential diagnosis arises
      from all types of immune-mediated skin lesions, opening up the broad spectrum of
      inflammatory systemic disease, such as vasculitis and sarcoidosis. Livedo like
      lesions and skin involvement in borreliosis are challenging to classify but of
      considerable clinical importance. The present review focuses on the description
      of underlying diseases as well as on diagnosis and differential diagnosis.
      Therapeutic considerations are discussed in less detail. 

PMID- 24026791
TI  - [The German law on reorganization of the pharmaceutical market (AMNOG):
      distinction between innovations and pseudoinnovations].

PMID- 24026792
TI  - [Polydipsia, increasing fatigue and a huge mediastinal tumor in a 49-year-old
      woman].
AB  - A 49-year-old woman presented with unspecific symptoms including polydipsia,
      increasing fatigue for several weeks, and vague abdominal pain. Serum calcium
      (5.30 mmol/l; normal range 2.00-2.60) and parathyroid hormone levels (> 2500.0
      ng/l; normal range 15.0-68.0) were extremely elevated. Imaging studies showed a
      huge mediastinal tumor. Based on these findings a hypercalcemic crisis caused by
      primary hyperparathyroidism was diagnosed. After intensive care treatment and
      further diagnostic procedures, the patient's parathyroid adenoma was removed by
      parathyroidectomy. The postoperative course was uneventful. 

PMID- 24026793
TI  - [A 55-year-old man with abdominal pain and fever].
AB  - A 55-year-old man was admitted for evaluation of chronic abdominal pain and
      fever. Computed tomography demonstrated a retroperitoneal inflammatory process
      involving the mesenteric root. Adipose tissue biopsy showed panniculitis
      mesenterica with granulomas. Further examinations confirmed the diagnosis of
      plasmocytoma type IgG kappa. Treatment with steroids (prednisolone), resulted in
      immediate improvement of pain and fever. Mesenteric panniculitis represents a
      paraneoplastic syndrome associated with non-Hodgkin lymphoma. 

PMID- 24026794
TI  - Enhanced therapy for primary and secondary syphilis: a longitudinal retrospective
      analysis of cure rates and associated factors.
AB  - For the treatment of early infectious syphilis, enhanced therapy with three
      dosages of benzathine penicillin G has been under consideration, particularly in
      the human immunodeficiency virus type 1 infected population (HIV-1). The
      serological outcome of 249 patients with primary and secondary syphilis treated
      with standard or enhanced therapy was analyzed retrospectively; 98% (139/142)
      achieved serological cure with a single dosage and 92% with enhanced therapy
      (P=0.033). In HIV-1 infected individuals, cure rates were 88% after a single
      dosage compared to 97% after three dosages (P=0.18). A fourfold decrease of
      Venereal Disease Research Laboratory (VDRL) titres was achieved within a median
      of 102 days after treatment initiation (SD=2; 95% CI=98-106). Patients aged over
      40 years were 5.5 times (OR=5.52; 95% CI=1.43-21.32; P=0.013) and patients with
      low baseline VDRL titres (<= 1:32) were 4 times (OR=4.25; 95% CI=1.21-14.87;
      P=0.024) more likely to experience serological failure.

PMID- 24026795
TI  - Acute generalised exanthematous pustulosis induced by Pneumocystis jirovecii
      pneumonia prophylaxis with dapsone.
AB  - We describe the case of HIV-1 infected patient presenting to hospital with a
      severe cutaneous adverse drug reaction shortly after commencing dapsone therapy
      as Pneumocystis jirovecii pneumonia prophylaxis. To the best of our knowledge,
      acute generalised exanthematous pustulosis has not been reported as a reaction to
      dapsone in the setting of HIV. 

PMID- 24026798
TI  - Photovoltaic properties of TiO2 loaded with glutathione-protected silver
      clusters.
AB  - Glutathione-protected Ag clusters (Ag15, Ag25 and Ag29) function as
      photosensitizers when they are adsorbed on TiO2 electrodes. [Co(bpy)3](2+) is the
      most appropriate electron donor among the cobalt complexes examined. Ag15
      clusters yielded the highest internal quantum efficiency of 28% at 460 nm in the
      presence of [Co(bpy)3](2+) as a donor. 

PMID- 24026796
TI  - Sexually transmitted infections in older people.

PMID- 24026799
TI  - From nongelating to gelating: synthesis and structural self-assembling property
      relationships of a homologous series of oligo(amide-triazole)s.
AB  - A homologous series of oligo(amide-triazole)s (OAT) [OAT-CO2H-2 n and OAT-COPrg
      (2 n+1)] with an increasing number of primary amide (CONH) and triazole hydrogen
      bonding functionalities was prepared by an iterative synthetic procedure. It was
      found that their self-assembly and thermoreversible gelation strength had a
      strong correlation to the number of hydrogen-bonding moieties in the oligomers.
      There also existed a threshold value of the number of CONH units, above which all
      the oligomers became organogelators. Hence, oligomers with <=4 CONH units are
      devoid of intermolecular hydrogen bonding and also non-organogelating, whereas
      those that contain >4 CONH units show intermolecular association and
      organogelating properties. For the organogelators, the T(gel) value increases
      monotonically with increasing number of CONH units. On the basis of FTIR
      measurements, both the CONH and triazole C-H groups were involved in the hydrogen
      bonding process. A mixed xerogel that consisted of a 1:1 weight ratio of two
      oligomers of different lengths (OAT-CO2H-6 and OAT-CO2H-12) was found to show
      microphase segregation according to differential scanning calorimetry, thus
      indicating that oligomers that bear a different number of hydrogen-bonding units
      exhibited self-sorting to maximize the extent of intermolecular hydrogen bonding
      in the xerogel state.

PMID- 24026800
TI  - Grape seed proanthocyanidins and metformin act by different mechanisms to promote
      insulin signaling in rats fed high calorie diet.
AB  - Key pathways like insulin signaling, AMP activated kinase (AMPK) activation and
      inflammatory signaling are involved in the complex pathological network of
      hepatic insulin resistance. Our aim is to investigate whether grape seed
      proanthocyanidins (GSP) and metformin (MET) target any of these pathways in
      insulin resistant rat liver. Albino Wistar rats were rendered insulin resistant
      by feeding a high fat-fructose diet (HFFD). Either GSP (100 mg/kg b.w), MET(50
      mg/kg b.w) or both were administered to insulin resistant rats as therapeutic
      options. HFFD-feeding caused hyperglycemia, hyperinsulinemia, increased
      gluconeogenesis, decreased tyrosine phosphorylation of insulin receptor-beta(IR
      beta) and insulin receptor substrate-1 (IRS-1) and increased serine
      phosphorylation of IRS-1. The association of p85alpha subunit of phosphotidyl
      inositol 3 kinase(PI3K) with IRS-1 and subsequent Akt phosphorylation were
      reduced while the expression of mitogen activated protein kinases (MAPK) were
      increased in HFFD rats. Both MET and GSP reduced hyperglycemia and
      hyperinsulinemia and improved glycolysis, tyrosine phosphorylation of IR-beta and
      IRS-1, IRS-1-PI3K association and Akt activation. However, activation of tumor
      necrosis factor-alpha, interleukin-6, leptin and suppressor of cytokine signaling
      3 and reduction in adiponectin caused by chronic HFFD feeding were reversed by
      GSP better than by MET. Activation of AMPK by GSP was much less compared to that
      by MET. These findings suggest that GSP might activate PI3K pathway and promote
      insulin action by reducing serine kinase activation and cytokine signaling and
      MET by targeting AMPK. The beneficial effects were enhanced during combination
      therapy. Thus, combination therapy with MET and GSP may be considered for the
      management of metabolic syndrome. 

PMID- 24026801
TI  - Systemic treatments for the prevention of venous thrombo-embolic events in
      paediatric cancer patients with tunnelled central venous catheters.
AB  - BACKGROUND: Venous thrombo-embolic events (VTEs) occur in 2.2% to 14% of
      paediatric cancer patients and cause significant morbidity and mortality. The
      malignant disease itself, the cancer treatment and the presence of central venous
      catheters (CVCs) increase the risk of VTE. OBJECTIVES: The primary objective of
      this review was to investigate the effects of preventive systemic treatments in
      paediatric cancer patients with tunnelled CVCs on (a)symptomatic VTE. Secondary
      objectives of this review were to investigate adverse effects of systemic
      treatments for the prevention of (a)symptomatic VTE in paediatric cancer patients
      with tunnelled CVCs; and to investigate the effects of systemic treatments in the
      prevention of (a)symptomatic VTE with CVC-related infection in paediatric cancer
      patients with tunnelled CVCs. SEARCH METHODS: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 8 2012),
      MEDLINE (1966 to August 2012) and EMBASE (1966 to August 2012). In addition, we
      searched reference lists from relevant articles and conference proceedings of the
      International Society for Paediatric Oncology (SIOP) (from 2006 to 2011), the
      American Society of Clinical Oncology (ASCO) (from 2006 to 2011), the American
      Society of Hematology (ASH) (from 2006 to 2011) and the International Society of
      Thrombosis and Haematology (ISTH) (from 2006 to 2011). We scanned the
      International Standard Randomised Controlled Trial Number (ISRCTN) Register and
      the National Institute of Health (NIH) Register for ongoing trials
      (www.controlled-trials.com) (August 2012), and we contacted the authors of
      eligible studies if additional information was required. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) and controlled clinical trials (CCTs)
      comparing systemic treatments to prevent venous thrombo-embolic events (VTEs) in
      paediatric cancer patients with tunnelled CVCs with a control intervention or no
      systemic treatment. For the description of adverse events, cohort studies were
      eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected studies, extracted data and performed risk of bias
      assessment of included studies. Analyses were performed according to the
      guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. MAIN
      RESULTS: Three RCTs and three CCTs (including 1291 children) investigated the
      prevention of VTE (low molecular weight heparin (LMWH) n = 134, antithrombin (AT)
      supplementation n = 37, low-dose warfarin n = 31, cryoprecipitate and/or fresh
      frozen plasma (FFP) supplementation n = 240, AT supplementation and LMWH n = 41).
      AT, cryoprecipitate and FFP were supplemented only in cases of AT or fibrinogen
      deficiency. Of the six included RCTs/CCTs, five investigated the prevention of
      VTE compared with no intervention (n = 737), and one CCT compared AT
      supplementation and LMWH with AT supplementation (n = 71). All studies had
      methodological limitations, and clinical heterogeneity between studies was
      noted.We found no significant effects of systemic treatments compared with no
      intervention in preventing (a)symptomatic VTE and no differences in adverse
      events (such as major and/or minor bleeding; none of the studies reported
      thrombocytopenia, heparin-induced thrombocytopenia (HIT), heparin-induced
      thrombocytopenia with thrombosis (HITT), death as a result of VTE, removal of CVC
      due to VTE, CVC-related infection, and post-thrombotic syndrome (PTS)) between
      experimental and control groups. Two studies with comparable participant groups
      and interventions were included for meta-analyses (n = 182). In the experimental
      group, 1/68 (1.5%) children were diagnosed with symptomatic VTE, as were 4/114
      (3.5%) in the control group (best case scenario: risk ratio (RR) 0.65, 95%
      confidence interval (CI) 0.09 to 4.78). These studies also evaluated asymptomatic
      CVC-related VTE: In the experimental group, 22/68 (32.4%) were diagnosed with
      asymptomatic VTE, as were 35/114 (30.7%) in the control group (best case
      scenario: RR 1.02, 95% CI 0.40 to 2.55). Heterogeneity was substantial for this
      analysis: I(2) = 73%.The attribution of LMWH to AT supplementation resulted in a
      significant reduction in symptomatic VTE (Fisher's exact test, two-sided P =
      0.028) without bleeding complications; asymptomatic VTE, thrombocytopenia, HIT,
      HITT, death as a result of VTE, removal of CVC due to VTE, CVC-related infection
      and PTS were not assessed.Four cohort studies were included for the evaluation of
      adverse events. Three studies provided information on bleeding episodes: One
      participant developed an ischaemo-haemorrhagic stroke. One study provided
      information on other adverse events: None occurred. AUTHORS' CONCLUSIONS: We
      found no significant effects of systemic treatments compared with no intervention
      in preventing (a)symptomatic VTE in paediatric oncology patients with CVCs.
      However, this could be a result of the low number of included participants, which
      resulted in low power. In one CCT, which compared one systemic treatment with
      another systemic treatment, we identified a significant reduction in symptomatic
      VTE with the addition of LMWH to AT supplementation.All studies investigated the
      prevalence of major and/or minor bleeding episodes, and none found a significant
      difference between study groups. None of the studies reported thrombocytopenia,
      HIT, HITT, death as a result of VTE, removal of CVC due to VTE, CVC-related
      infection or PTS among participants.On the basis of currently available evidence,
      we are not able to give recommendations for clinical practise. Additional well
      designed international RCTs are needed to further explore the effects of systemic
      treatments in preventing VTE. Future studies should aim for adequate power with
      attainable sample sizes. The incidence of symptomatic VTE is relatively low;
      therefore, it might be necessary to select participants with thrombotic risk
      factors or to investigate asymptomatic VTE instead.

PMID- 24026802
TI  - Sensing sociality in dogs: what may make an interactive robot social?
AB  - This study investigated whether dogs would engage in social interactions with an
      unfamiliar robot, utilize the communicative signals it provides and to examine
      whether the level of sociality shown by the robot affects the dogs' performance.
      We hypothesized that dogs would react to the communicative signals of a robot
      more successfully if the robot showed interactive social behaviour in general
      (towards both humans and dogs) than if it behaved in a machinelike, asocial way.
      The experiment consisted of an interactive phase followed by a pointing session,
      both with a human and a robotic experimenter. In the interaction phase, dogs
      witnessed a 6-min interaction episode between the owner and a human experimenter
      and another 6-min interaction episode between the owner and the robot. Each
      interaction episode was followed by the pointing phase in which the human/robot
      experimenter indicated the location of hidden food by using pointing gestures
      (two-way choice test). The results showed that in the interaction phase, the
      dogs' behaviour towards the robot was affected by the differential exposure. Dogs
      spent more time staying near the robot experimenter as compared to the human
      experimenter, with this difference being even more pronounced when the robot
      behaved socially. Similarly, dogs spent more time gazing at the head of the robot
      experimenter when the situation was social. Dogs achieved a significantly lower
      level of performance (finding the hidden food) with the pointing robot than with
      the pointing human; however, separate analysis of the robot sessions suggested
      that gestures of the socially behaving robot were easier for the dogs to
      comprehend than gestures of the asocially behaving robot. Thus, the level of
      sociality shown by the robot was not enough to elicit the same set of social
      behaviours from the dogs as was possible with humans, although sociality had a
      positive effect on dog-robot interactions. 

PMID- 24026803
TI  - Increase of the phytase production by Aspergillus japonicus and its biocatalyst
      potential on chicken feed treatment.
AB  - Phytase hydrolyzes phytic acid from the plant components of animal feed,
      releasing inorganic phosphorus. The phytase production by Aspergillus japonicus
      was optimized using Plackett-Burman designs (PBD), composite central rotational
      designs (CCRD), and response surface methodology from standard Czapek medium. The
      enzyme was applied in broiler chicken and laying hen foods. Analysis from PBD
      showed that KH2 PO2, MgSO4  . 7H2O, and yeast extract had significant influences
      on phytase secretion (p < 0.05). The best results from the CCRD experiments were
      obtained using (A) 0.040% KH2 PO4, (B) 0.050% MgSO4  . 7H2O, and (C) 0.040% yeast
      extract, enhancing in 49-53 U mg(-1) protein. The determination coefficient
      (R(2)) was 0.92 and Fcalc was 7.48 times greater than Flisted . Thus, the reduced
      coded model: Y (U mg-1) = 50.29 + 4.30A - 3.35(A)2 - 4.80(B)2 + 5.62C - 4.26(C)2
      was considered predictive and statistically significant (p < 0.05). The optimized
      culture medium increased the phytase yield in 250%. A. japonicus phytase released
      high levels of Pi from broiler chicken and laying hen food. A. japonicus is an
      excellent phytase producer in a culture medium using inexpensive components and
      agricultural wastes. Therefore, these results provide sound arguments for the
      formulation of a low cost culture medium for phytase production.

PMID- 24026805
TI  - Nietzsche, illness and the body's quest for narrative.
AB  - This paper explores Nietzsche's approach to the question of illness. It develops
      an account of Nietzsche's ideas in the wake of Arthur W. Frank's discussion of
      the shortcomings of modern medicine and narrative theory. Nietzsche's approach to
      illness is then explored in the context of On the Genealogy of Morality and his
      conception of the human being as "the sick animal". This account, it is argued,
      allows for Nietzsche to develop a conception of suffering that refuses to reduce
      it to modernist restitutive conceptions of well-being. Instead, Nietzsche
      advocates a more nuanced conception of varying degrees of health. This, it is
      argued, can be developed into a model that allows for a more satisfying
      conception of the relation between medical practitioner and patient. 

PMID- 24026804
TI  - Human papillomavirus infection in women in four regions of Senegal.
AB  - Cervical cancer is the most frequent cancer among women in Senegal. However,
      there are few data concerning the human papillomavirus (HPV) types inducing
      neoplasia and cervical cancers and their prevalence in the general population of
      Senegal. The aim of this study is to determine the prevalence of HPV infection in
      Senegalese women aged 18 years and older in Dakar Region and three other regions.
      Cervical samples were collected from 498 women aged 18-80 years (mean, 42.1
      years) in Dakar Region. Also, 438 samples were collected from three other
      regions: Thies, Saint-Louis, and Louga. The samples were screened for 21 HPV
      genotypes using an HPV type-specific E7 PCR bead-based multiplex genotyping assay
      (TS-MPG). The prevalence of high risk (HR)-HPV in Dakar Region was 17.4%. HPV 52
      (3.2%) was the most prevalent HPV type, followed by HPV 31 (3.0%) and HPV 16, 45,
      and 53 (all 2.8%). In the Thies, Saint-Louis, and Louga Regions, the prevalence
      of HR-HPV was 23.2%, 13.1%, and 19.4%, respectively. The study revealed the
      specificity of HPV prevalence in Dakar Region and other regions of Senegal. The
      observed patterns show some differences compared with other regions of the world.
      These findings raise the possibility that, in addition to HPV 16 and HPV 18,
      other HPV types should be considered for a vaccination program in Senegal.
      However, additional studies to determine the HPV type distribution in cervical
      cancer specimens in Senegal are required to further corroborate this hypothesis.

PMID- 24026806
TI  - [When the pain is gone then you are dead].

PMID- 24026808
TI  - Eliminating host-mediated effects demonstrates Bt maize producing Cry1F has no
      adverse effects on the parasitoid Cotesia marginiventris.
AB  - The fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae),
      is an important pest of maize in the United States and many tropical areas in the
      western hemisphere. In 2001, Herculex I((r)) (Cry1F) maize was commercially
      planted in the United States to control Lepidoptera, including S. frugiperda. In
      2006, a population of S. frugiperda was discovered in Puerto Rico that had
      evolved resistance to Cry1F maize in the field, making it the first well
      documented case of an insect with field resistance to a plant producing protein
      from Bacillus thuringiensis (Bt). Using this resistant population, we conducted
      tri-trophic studies with a natural enemy of S. frugiperda. By using resistant S.
      frugiperda, we were able to overcome possible prey-mediated effects and avoid
      concerns about potential differences in laboratory- or field-derived Bt
      resistance. We used the Cry1F-resistant S. frugiperda to evaluate effects of
      Cry1F on Cotesia marginiventris (Cresson) (Hymenoptera: Braconidae), a larval
      endoparasitoid of S. frugiperda, over five generations. Our results clearly
      demonstrate that Cry1F maize does not affect development, parasitism,
      survivorship, sex ratio, longevity or fecundity of C. marginiventris when they
      parasitize Cry1F maize-fed S. frugiperda. Furthermore, the level of Cry1F protein
      in the leaves was strongly diluted when transferred from Bt maize to S.
      frugiperda and was not detected in larvae, cocoons or adults of C.
      marginiventris. Our results refute previous reports of C. marginiventris being
      harmed by Bt proteins and suggest that such results were caused by prey-mediated
      effects due to using Bt-susceptible lepidopteran hosts. 

PMID- 24026807
TI  - [Gender differences in acute and chronic pain conditions. Implications for
      diagnosis and therapy].
AB  - Gender differences can influence incidence and outcome of acute and chronic pain
      conditions. The reasons are to be found in genetic factors, hormonal effects and
      differences in anatomy and physiology. Furthermore differences relating to
      psychiatric comorbidities (i.e. depression) and psychosocial factors (roles,
      coping strategies) have been demonstrated. Men and women differ in the response
      to drugs and other treatments. They are differently affected by side effects of
      drugs. There is a gender bias in diagnosis and therapy. There is a need to study
      the influence of gender, age and race in order to optimize treatment towards a
      more individualized therapy. This article highlights already identified
      differences. 

PMID- 24026809
TI  - Parieto-frontal circuits during observation of hidden and visible motor acts in
      children. A high-density EEG source imaging study.
AB  - Several studies showed that in the human brain specific premotor and parietal
      areas are activated during the execution and observation of motor acts. The
      activation of this premotor-parietal network displaying the so-called Mirror
      Mechanism (MM) was proposed to underpin basic forms of action understanding.
      However, the functional properties of the MM in children are still largely
      unknown. In order to address this issue, we recorded high-density EEG from 12
      children (6 female, 6 male; average age 10.5, SD +/-2.15). Data were collected
      when children observed video clips showing hands grasping objects in two
      different experimental conditions: (1) Full Vision, in which the motor act was
      fully visible; (2) Hidden, in which the interaction between the hand and the
      object was not visible. Event-related potentials (ERPs) and topographic map
      analyses were used to investigate the temporal pattern of the ERPs and their
      brain source of localization, employing a children template of the Montreal
      Neurological Institute. Results showed that two different parieto-premotor
      circuits are activated by the observation of object-related hand reaching-to
      grasping motor acts in children. The first circuit comprises the ventral premotor
      and the inferior parietal cortices. The second one comprises the dorsal premotor
      and superior parietal cortices. The activation of both circuits is differently
      lateralized and modulated in time, and influenced by the amount of visual
      information available about the hand grasping-related portion of the observed
      motor acts. 

PMID- 24026810
TI  - Pulse-oximetry screening to detect critical congenital heart disease in the
      neonatal intensive care unit.
AB  - The current pulse-oximetry screening (POS) protocol for detection of critical
      congenital heart defects (CCHDs) is recommended only for newborns in well-infant
      and intermediate care nurseries, and there is no evidence-based protocol for
      infants discharged from the neonatal intensive care unit (NICU). The objectives
      of this study were to examine the efficacy of the current screening protocol in a
      NICU setting and to determine the impact of a unit protocol on the use of POS.
      Charts of 250 infants previous (group 1) and 250 infants after (group 2) the
      protocol implementation were reviewed. The results of screening test and
      preductal and postductal SpO2 were recorded for screened infants. A predischarge
      SpO2 value was recorded if screening was not performed. No infant in group 1 had
      POS. All eligible infants in group 2 received screening and passed. Preductal and
      postductal oxygen saturations in preterm infants at discharge were similar to
      saturations in late preterm and term infants. These results show that oxygen
      saturations at discharge in late preterm and term infants requiring admission to
      the NICU are similar to infants with no morbidities and that the current POS
      protocol can be safely used for these infants at discharge from the NICU. This
      study also confirms that preductal and postductal oxygen saturations at discharge
      in preterm infants are not different from those in late preterm and term infants.
      A unit protocol is likely to be more effective than relying on individual
      providers to ensure that all infants undergo POS for detection of CCHD.

PMID- 24026812
TI  - Circularly polarized luminescence in supramolecular assemblies of chiral
      bichromophoric perylene bisimides.
AB  - Chiral bichromophoric perylene bisimides are demonstrated as active materials of
      circularly polarized emission. The bichromophoric system exhibited circularly
      polarized luminescence with dissymmetry factors typical of that of similar
      organic chiral chromophoric systems in the monomeric state. Variation in solvent
      composition led to the formation of stably soluble helical aggregates through
      intermolecular interactions. A large enhancement in the dissymmetry of circularly
      polarized luminescence was exhibited by the aggregated structures both in the
      solution and solid states. The sum of excitonic couplings between the individual
      chromophoric units in the self-assembled state results in relatively large
      dissymmetry in the circularly polarized luminescence, thereby giving rise to
      enhanced dissymmetry factors for the aggregated structures. The spacer between
      chiral center and chromophoric units played a crucial role in the effective
      enhancement of chiroptical properties in the self-assembled structures. These
      materials might provide opportunities for the design of a new class of functional
      bichromophoric organic nanoarchitectures that can find potential applications in
      the field of chiroptical memory and light-emitting devices based on
      supramolecular electronics. 

PMID- 24026811
TI  - Requirement for commissureless2 function during dipteran insect nerve cord
      development.
AB  - BACKGROUND: In Drosophila melanogaster, commissureless (comm) function is
      required for proper nerve cord development. Although comm orthologs have not been
      identified outside of Drosophila species, some insects possess orthologs of
      Drosophila comm2, which may also regulate embryonic nerve cord development. Here,
      this hypothesis is explored through characterization of comm2 genes in two
      disease vector mosquitoes. RESULTS: Culex quinquefasciatus (West Nile and
      lymphatic filiariasis vector) has three comm2 genes that are expressed in the
      developing nerve cord. Aedes aegypti (dengue and yellow fever vector) has a
      single comm2 gene that is expressed in commissural neurons projecting axons
      toward the midline. Loss of comm2 function in both A. aegypti and D. melanogaster
      was found to result in loss of commissure defects that phenocopy the frazzled
      (fra) loss of function phenotypes observed in both species. Loss of fra function
      in either insect was found to result in decreased comm2 transcript levels during
      nerve cord development. CONCLUSIONS: The results of this investigation suggest
      that Fra down-regulates repulsion in precrossing commissural axons by regulating
      comm2 levels in both A. aegypti and D. melanogaster, both of which require Comm2
      function for proper nerve cord development.

PMID- 24026814
TI  - Differential effect of cognitive training on executive functions and reading
      abilities in children with ADHD and in children with ADHD comorbid with reading
      difficulties.
AB  - The comorbidity of ADHD and reading difficulties (ADHD + RD) is believed to be a
      disability distinct from ADHD alone, with unique challenges faced by individuals
      suffering from one disability versus the other. We aimed to examine the
      differential effect of 8 weeks of cognitive training on reading abilities and on
      executive functions, through use of the Wisconsin task, in children with ADHD and
      in children with ADHD + RD. Greater impairments in reading and executive
      functions, especially in speed of processing, were found in the comorbid group at
      baseline. The comorbid group showed greater improvements in most measures after
      training as well. We propose that the cognitive training used in the present
      study affected not only the immediate abilities of executive functioning but also
      the secondary ability of reading, especially in the comorbid group, by improving
      in particular, speed of processing. We suggest that a differential approach
      should be taken when treating children with ADHD + RD versus treating ADHD
      children. 

PMID- 24026813
TI  - An Analysis of the Barkley Deficits in Executive Functioning Scale in a College
      Population: Does It Predict Symptoms of ADHD Better Than a Visual-Search Task?
AB  - OBJECTIVE: Executive functioning (EF) deficits have been associated with ADHD.
      However, disagreement exists concerning the extent to which cognitive tests of EF
      accurately reflect a diagnosis of ADHD. Barkley developed the Barkley Deficits in
      Executive Functioning Scale (BDEFS) by categorizing the meta-construct of EF into
      five subdomains. This study investigated the incremental validity of the BDEFS in
      predicting symptoms of ADHD compared with a visual-search task. We also
      investigated patterns among the five BDEFS domains. METHOD: One hundred and
      sixteen college students completed a visual-search task and the BDEFS and
      reported on their symptoms of ADHD. RESULTS: (a) BDEFS total scores significantly
      predicted total ADHD symptoms, whereas the visual-search task failed to predict
      ADHD symptoms. (b) The BDEFS demonstrated significant correlations with symptoms
      of ADHD in expected patterns. CONCLUSION: This study provides evidence of
      validity for the BDEFS in a college sample.

PMID- 24026815
TI  - Patterns of spread of influenza A in Canada.
AB  - Understanding spatial patterns of influenza transmission is important for
      designing control measures. We investigate spatial patterns of laboratory
      confirmed influenza A across Canada from October 1999 to August 2012. A
      statistical analysis (generalized linear model) of the seasonal epidemics in this
      time period establishes a clear spatio-temporal pattern, with influenza emerging
      earlier in western provinces. Early emergence is also correlated with low
      temperature and low absolute humidity in the autumn. For the richer data from the
      2009 pandemic, a mechanistic mathematical analysis, based on a transmission
      model, shows that both school terms and weather had important effects on pandemic
      influenza transmission. 

PMID- 24026816
TI  - The walk and jump of Equisetum spores.
AB  - Equisetum plants (horsetails) reproduce by producing tiny spherical spores that
      are typically 50 um in diameter. The spores have four elaters, which are flexible
      ribbon-like appendages that are initially wrapped around the main spore body and
      that deploy upon drying or fold back in humid air. If elaters are believed to
      help dispersal, the exact mechanism for spore motion remains unclear in the
      literature. In this manuscript, we present observations of the 'walks' and
      'jumps' of Equisetum spores, which are novel types of spore locomotion mechanisms
      compared to the ones of other spores. Walks are driven by humidity cycles, each
      cycle inducing a small step in a random direction. The dispersal range from the
      walk is limited, but the walk provides key steps to either exit the sporangium or
      to reorient and refold. Jumps occur when the spores suddenly thrust themselves
      after being tightly folded. They result in a very efficient dispersal: even
      spores jumping from the ground can catch the wind again, whereas non-jumping
      spores stay on the ground. The understanding of these movements, which are solely
      driven by humidity variations, conveys biomimetic inspiration for a new class of
      self-propelled objects. 

PMID- 24026817
TI  - Increasing arboreality with altitude: a novel biogeographic dimension.
AB  - Biodiversity is spatially organized by climatic gradients across elevation and
      latitude. But do other gradients exist that might drive biogeographic patterns?
      Here, we show that rainforest's vertical strata provide climatic gradients much
      steeper than those offered by elevation and latitude, and biodiversity of
      arboreal species is organized along this gradient. In Philippine and Singaporean
      rainforests, we demonstrate that rainforest frogs tend to shift up in the
      rainforest strata as altitude increases. Moreover, a Philippine-wide dataset of
      frog distributions shows that frog assemblages become increasingly arboreal at
      higher elevations. Thus, increased arboreality with elevation at broad
      biogeographic scales mirrors patterns we observed at local scales. Our proposed
      'arboreality hypothesis' suggests that the ability to exploit arboreal habitats
      confers the potential for larger geographical distributions because species can
      shift their location in the rainforest strata to compensate for shifts in
      temperature associated with elevation and latitude. This novel finding may help
      explain patterns of species richness and abundance wherever vegetation produces a
      vertical microclimatic gradient. Our results further suggest that global warming
      will 'flatten' the biodiversity in rainforests by pushing arboreal species
      towards the cooler and wetter ground. This 'flattening' could potentially have
      serious impacts on forest functioning and species survival. 

PMID- 24026818
TI  - Large-scale phylogenetic analyses reveal the causes of high tropical amphibian
      diversity.
AB  - Many groups show higher species richness in tropical regions but the underlying
      causes remain unclear. Despite many competing hypotheses to explain latitudinal
      diversity gradients, only three processes can directly change species richness
      across regions: speciation, extinction and dispersal. These processes can be
      addressed most powerfully using large-scale phylogenetic approaches, but most
      previous studies have focused on small groups and recent time scales, or did not
      separate speciation and extinction rates. We investigate the origins of high
      tropical diversity in amphibians, applying new phylogenetic comparative methods
      to a tree of 2871 species. Our results show that high tropical diversity is
      explained by higher speciation in the tropics, higher extinction in temperate
      regions and limited dispersal out of the tropics compared with colonization of
      the tropics from temperate regions. These patterns are strongly associated with
      climate-related variables such as temperature, precipitation and ecosystem
      energy. Results from models of diversity dependence in speciation rate suggest
      that temperate clades may have lower carrying capacities and may be more
      saturated (closer to carrying capacity) than tropical clades. Furthermore, we
      estimate strikingly low tropical extinction rates over geological time scales, in
      stark contrast to the dramatic losses of diversity occurring in tropical regions
      presently. 

PMID- 24026819
TI  - Food vibrations: Asian spice sets lips trembling.
AB  - Szechuan pepper, a widely used ingredient in the cuisine of many Asian countries,
      is known for the tingling sensation it induces on the tongue and lips. While the
      molecular mechanism by which Szechuan pepper activates tactile afferent fibres
      has been clarified, the tingling sensation itself has been less studied, and it
      remains unclear which fibres are responsible. We investigated the somatosensory
      perception of tingling in humans to identify the characteristic temporal
      frequency and compare this to the established selectivity of tactile afferents.
      Szechuan pepper was applied to the lower lip of participants. Participants judged
      the frequency of the tingling sensation on the lips by comparing this with the
      frequencies of mechanical vibrations applied to their right index finger. The
      perceived frequency of the tingling was consistently at around 50 Hz,
      corresponding to the range of tactile RA1 afferent fibres. Furthermore,
      adaptation of the RA1 channel by prolonged mechanical vibration reliably reduced
      the tingling frequency induced by Szechuan pepper, confirming that the frequency
      specific tactile channel is shared between Szechuan pepper and mechanical
      vibration. Combining information about molecular reactions at peripheral
      receptors with quantitative psychophysical measurement may provide a unique
      method for characterizing unusual experiences by decomposing them into
      identifiable minimal units of sensation. 

PMID- 24026820
TI  - Do smart birds stress less? An interspecific relationship between brain size and
      corticosterone levels.
AB  - Vertebrates respond to unpredictable noxious environmental stimuli by increasing
      secretion of glucocorticoids (CORT). Although this hormonal stress response is
      adaptive, high levels of CORT may induce significant costs if stressful
      situations are frequent. Thus, alternative coping mechanisms that help buffer
      individuals against environmental stressors may be selected for when the costs of
      CORT levels are elevated. By allowing individuals to identify, anticipate and
      cope with the stressful circumstances, cognition may enable stress-specific
      behavioural coping. Although there is evidence that behavioural responses allow
      animals to cope with stressful situations, it is unclear whether or not cognition
      reduces investment in the neuroendocrine stress response. Here, we report that in
      birds, species with larger brains relative to their body size show lower baseline
      and peak CORT levels than species with smaller brains. This relationship is
      consistent across life-history stages, and cannot be accounted for by differences
      in life history and geographical latitude. Because a large brain is a major
      feature of birds that base their lifetime in learning new things, our results
      support the hypothesis that enhanced cognition represents a general alternative
      to the neuroendocrine stress response. 

PMID- 24026821
TI  - Sexual and parental antagonism shape genomic architecture.
AB  - Populations with two sexes are vulnerable to a pair of genetic conflicts: sexual
      antagonism that can arise when alleles have opposing fitness effects on females
      and males; and parental antagonism that arises when alleles have opposing fitness
      effects when maternally and paternally inherited. This paper extends previous
      theoretical work that found stable linkage disequilibrium (LD) between sexually
      antagonistic loci. We find that LD is also generated between parentally
      antagonistic loci, and between sexually and parentally antagonistic loci, without
      any requirement of epistasis. We contend that the LD in these models arises from
      the admixture of gene pools subject to different selective histories. We also
      find that polymorphism maintained by parental antagonism at one locus expands the
      opportunity for polymorphism at a linked locus experiencing parental or sexual
      antagonism. Taken together, our results predict the chromosomal clustering of
      loci that segregate for sexually and parentally antagonistic alleles. Thus,
      genetic conflict may play a role in the evolution of genomic architecture. 

PMID- 24026822
TI  - Explaining the distribution of breeding and dispersal syndromes in conifers.
AB  - The evolution of plants exhibiting different sexes, or dioecy, is correlated with
      a number of ecological and life-history traits such as woody growth form and
      animal-dispersed seeds, but the underlying causes of these associations are
      unclear. Previous work in seed plants has suggested that the evolution of fleshy
      cones or seeds may favour dioecy. In this study, we use a well-sampled molecular
      phylogeny of conifers to show that although dioecy and fleshiness strongly co
      occur at the species level, this relationship has not resulted from numerous
      separate origins of this trait combination or from differential rates of
      diversification. Instead, we suggest that two character combinations-the
      ancestral dry-monoecious condition and the derived fleshy-dioecious condition
      have persisted in conifers longer than other combinations over evolutionary time.
      The persistence of these trait combinations appears to reflect differences in the
      rate of successful transition into and out of these character states over time,
      as well as the geographical restriction of species with rare combinations and
      their consequent vulnerability to extinction. In general, we argue that such
      persistence explanations should be considered alongside 'key innovation'
      hypotheses in explaining the phylogenetic distribution of traits. 

PMID- 24026824
TI  - A cure for the plague of parameters: constraining models of complex population
      dynamics with allometries.
AB  - A major goal of ecology is to discover how dynamics and structure of multi
      trophic ecological communities are related. This is difficult, because whole
      community data are limited and typically comprise only a snapshot of a community
      instead of a time series of dynamics, and mathematical models of complex system
      dynamics have a large number of unmeasured parameters and therefore have been
      only tenuously related to real systems. These are related problems, because long
      time-series, if they were commonly available, would enable inference of
      parameters. The resulting 'plague of parameters' means most studies of multi
      species population dynamics have been very theoretical. Dynamical models
      parametrized using physiological allometries may offer a partial cure for the
      plague of parameters, and these models are increasingly used in theoretical
      studies. However, physiological allometries cannot determine all parameters, and
      the models have also rarely been directly tested against data. We confronted a
      model of community dynamics with data from a lake community. Many important
      empirical patterns were reproducible as outcomes of dynamics, and were not
      reproducible when parameters did not follow physiological allometries. Results
      validate the usefulness, when parameters follow physiological allometries, of
      classic differential-equation models for understanding whole-community dynamics
      and the structure-dynamics relationship. 

PMID- 24026823
TI  - Cryptic species of Archinome (Annelida: Amphinomida) from vents and seeps.
AB  - Since its description from the Galapagos Rift in the mid-1980s, Archinome rosacea
      has been recorded at hydrothermal vents in the Pacific, Atlantic and Indian
      Oceans. Only recently was a second species described from the Pacific Antarctic
      Ridge. We inferred the identities and evolutionary relationships of Archinome
      representatives sampled from across the hydrothermal vent range of the genus,
      which is now extended to cold methane seeps. Species delimitation using
      mitochondrial cytochrome c oxidase subunit I (COI) recovered up to six lineages,
      whereas concatenated datasets (COI, 16S, 28S and ITS1) supported only four or
      five of these as clades. Morphological approaches alone were inconclusive to
      verify the identities of species owing to the lack of discrete diagnostic
      characters. We recognize five Archinome species, with three that are new to
      science. The new species, designated based on molecular evidence alone, include:
      Archinome levinae n. sp., which occurs at both vents and seeps in the east
      Pacific, Archinome tethyana n. sp., which inhabits Atlantic vents and Archinome
      jasoni n. sp., also present in the Atlantic, and whose distribution extends to
      the Indian and southwest Pacific Oceans. Biogeographic connections between vents
      and seeps are highlighted, as are potential evolutionary links among populations
      from vent fields located in the east Pacific and Atlantic Oceans, and Atlantic
      and Indian Oceans; the latter presented for the first time. 

PMID- 24026826
TI  - Morphological and biomechanical disparity of crocodile-line archosaurs following
      the end-Triassic extinction.
AB  - Mesozoic crurotarsans exhibited diverse morphologies and feeding modes,
      representing considerable ecological diversity, yet macroevolutionary patterns
      remain unexplored. Here, we use a unique combination of morphological and
      biomechanical disparity metrics to quantify the ecological diversity and trophic
      radiations of Mesozoic crurotarsans, using the mandible as a morpho-functional
      proxy. We recover three major trends. First, the diverse assemblage of Late
      Triassic crurotarsans was morphologically and biomechanically disparate, implying
      high levels of ecological variation; but, following the end-Triassic extinction,
      disparity declined. Second, the Jurassic radiation of marine thalattosuchians
      resulted in very low morphological disparity but moderate variation in jaw
      biomechanics, highlighting a hydrodynamic constraint on mandibular form. Third,
      during the Cretaceous terrestrial radiations of neosuchians and notosuchians,
      mandibular morphological variation increased considerably. By the Late
      Cretaceous, crocodylomorphs evolved a range of morphologies equalling Late
      Triassic crurotarsans. By contrast, biomechanical disparity in the Cretaceous did
      not increase, essentially decoupling from morphology. This enigmatic result could
      be attributed to biomechanical evolution in other anatomical regions (e.g.
      cranium, dentition or postcranium), possibly releasing the mandible from
      selective pressures. Overall, our analyses reveal a complex relationship between
      morphological and biomechanical disparity in Mesozoic crurotarsans that
      culminated in specialized feeding ecologies and associated lifestyles. 

PMID- 24026825
TI  - Holarctic genetic structure and range dynamics in the woolly mammoth.
AB  - Ancient DNA analyses have provided enhanced resolution of population histories in
      many Pleistocene taxa. However, most studies are spatially restricted, making
      inference of species-level biogeographic histories difficult. Here, we analyse
      mitochondrial DNA (mtDNA) variation in the woolly mammoth from across its
      Holarctic range to reconstruct its history over the last 200 thousand years
      (kyr). We identify a previously undocumented major mtDNA lineage in Europe, which
      was replaced by another major mtDNA lineage 32-34 kyr before present (BP).
      Coalescent simulations provide support for demographic expansions at
      approximately 121 kyr BP, suggesting that the previous interglacial was an
      important driver for demography and intraspecific genetic divergence.
      Furthermore, our results suggest an expansion into Eurasia from America around 66
      kyr BP, coinciding with the first exposure of the Bering Land Bridge during the
      Late Pleistocene. Bayesian inference indicates Late Pleistocene demographic
      stability until 20-15 kyr BP, when a severe population size decline occurred. 

PMID- 24026828
TI  - Effect of spironolactone on cardiovascular complications associated with type-2
      diabetes in rats.
AB  - We have studied the effect spironolactone (20 mg/kg/day) on cardiovascular
      complications in neonatal model of diabetes in rats, induced by administering 90
      mg/kg streptozotocin (STZ), i.p. in 2 day old rats. Diabetes was checked after 12
      weeks. At the end of 8 weeks of treatment, various biochemical and cardiac
      parameters were measured. STZ produced hyperglycemia, hyperinsulinemia,
      dyslipidemia, increased creatinine, cardiac enzyme and C-reactive protein (CRP)
      levels, worsened hemodynamic parameters, cardiac hypertrophy and oxidative
      stress. Chronic treatment with spironolactone significantly reduced serum glucose
      levels but did not alter insulin levels. It also significantly prevented the
      dyslipidemia and reduced elevated Lactate de-hydrogenase, creatinine kinase, CRP
      and creatinine levels. Chronic treatment with spironolactone prevented STZ
      induced hypertension, tachycardia and elevated rate of pressure development and
      decay. Spironolactone also produced beneficial effect by preventing cardiac
      hypertrophy as evident from left ventricular collagen levels, cardiac and left
      ventricular hypertrophic indices and prevented oxidative stress. In conclusion,
      our data suggests that spironolactone prevents STZ induced metabolic
      abnormalities and cardiovascular complications in animal model of type 2
      diabetes. 

PMID- 24026829
TI  - Endurance exercise alters cellular immune status and resistin concentrations in
      men suffering from non-insulin-dependent type 2 diabetes.
AB  - It has been demonstrated that alterations of adipocytokines can alter immune
      status in type 2 diabetes. The present study investigated changes of
      adipocytokine plasma concentrations and cellular immune status in overweight men,
      suffering from non-insulin dependent type 2 diabetes (n=14, age 61.0+/-8.7 years,
      BMI 31.1+/-3.5 kg/cm2). Subjects underwent a 3 months endurance exercise
      intervention (twice per week for up to 45 min) cycling at a heart rate
      corresponding to a 2 mmol/l lactate threshold. Before and after the intervention
      testing for adipocytokines (leptin, adiponectin, resistin) and cellular immune
      status (including T memory-cells and regulative T-cells) was performed by RIA and
      FACS accordingly.The exercise intervention improved anthropometric and metabolic
      parameters of all subjects. We observed a significant decline for resistin and
      for the CD19+ B-cells. The CD4+CD25+CD127low Treg-cells decreased, however not
      statistically significant. All other parameters remained unchanged.In conclusion,
      even though only training twice a week, the exercise affected parts of the
      cellular immune system as well as resistin levels in men suffering from non
      insulin dependent type 2 diabetes. 

PMID- 24026830
TI  - Creating a "pull request" for collaborative care.

PMID- 24026833
TI  - State mental health policy: an interactive tool to estimate costs and resources
      for a first-episode psychosis initiative in New York State.
AB  - The New York State Office of Mental Health (OMH), which is a partner in the RAISE
      (Recovery After Initial Schizophrenia Episode) Connection program, is scaling up
      services for individuals with first-episode psychosis (FEP) and must estimate the
      number of specialized treatment teams needed across the state. This column
      describes a modeling tool that allows users to input various estimates for
      relevant variables and see the impact on projections for number of FEP teams
      needed and the costs of those teams. The interactive, Excel-based tool can be
      adapted for other treatment settings and programs. 

PMID- 24026834
TI  - Personal accounts: toward trauma relief and resolution: an experience at the
      Trauma Resolution Center.

PMID- 24026832
TI  - Integrated care: integrating general medical and behavioral health care: the New
      York State perspective.
AB  - This column describes recent policy and program initiatives implemented by the
      New York State Office of Mental Health to enhance integration of general medical
      and behavioral health services throughout the state public mental health system.
      Recent initiatives were implemented to improve access to health and wellness
      oriented services, redesign managed care programs to improve engagement and
      retention of high-need individuals, and raise the bar on quality while lowering
      costs. Taken as a whole, these initiatives represent a 21st-century
      transformation of a state mental health authority into an accountable and more
      fully integrated public health delivery system. 

PMID- 24026835
TI  - Development and validation of a Housing First fidelity survey.
AB  - OBJECTIVES: Programs that use the Housing First model are being implemented
      throughout the United States and internationally. The authors describe the
      development and validation of a Housing First fidelity survey. METHODS: A 46-item
      survey was developed to measure fidelity across five domains: housing process and
      structure, separation of housing and services, service philosophy, service array,
      and team structure. The survey was administered to staff and clients of 93
      supported-housing programs in California. Exploratory and confirmatory factor
      analyses were used to identify the items and model structure that best fit the
      data. RESULTS: Sixteen items were retained in a two-factor model, one related to
      approach to housing, separation of housing and services, and service philosophy
      and one related to service array and team structure. CONCLUSIONS: Our survey
      mapped program practices by using a common metric that captured variation in
      fidelity to Housing First across a large-scale implementation of supported
      housing programs.

PMID- 24026836
TI  - Transitional case management for reducing recidivism of individuals with mental
      disorders and multiple misdemeanors.
AB  - OBJECTIVE: The purpose of this study was to measure the impact of a transitional
      case management (TCM) program targeted to individuals with mental disorders and
      multiple arrests for misdemeanor offenses. METHODS: The sample included 178
      individuals who were diverted from jail at arraignment (N=125) or who voluntarily
      enrolled in TCM (N=53). Number of arrests and case management sessions attended
      were compared. RESULTS: The mean +/- SD number of arrests of the 178 participants
      declined by 31% from the 12 months preenrollment to the 12 months postenrollment.
      Lifetime arrests and age were significant factors in the count of arrests
      postenrollment. Diverted and voluntary participants had similar numbers of
      postenrollment arrests (2.5 +/- 3.0 and 2.5 +/- 3.5, respectively). Differences
      in mean postenrollment arrests for diverted participants who completed or did not
      complete TCM were not significant. Diverted and voluntary participants received
      an equivalent mean number of case management sessions. CONCLUSIONS: Individuals
      in TCM experienced a reduction in arrests in the 12 months postenrollment.

PMID- 24026837
TI  - Financial victimization of adults with severe mental illness.
AB  - OBJECTIVE: People with severe mental illness are vulnerable to having other
      people directly take or misappropriate their disability payments. This study
      investigated the prevalence of different types of financial victimization and the
      client characteristics associated with being financially victimized. METHODS:
      Adults (N=122) receiving inpatient or intensive outpatient psychiatric treatment
      who received Social Security disability payments completed assessments about
      money management and victimization. A path model was used to estimate the
      association of victimization with participant characteristics. RESULTS: Seventy
      percent of participants experienced at least one type of financial victimization
      in the preceding 28 days; 35% ran out of money because of victimization.
      Victimization was significantly associated with being younger, having had more
      psychiatric hospitalizations, having more recent alcohol use, and, most robustly,
      having problems managing money (beta=.52, p<.01). CONCLUSIONS: Financial
      victimization of disability recipients in acute care settings is common and more
      likely among people with recent substance use and difficulty managing their
      funds.

PMID- 24026838
TI  - The diagnosis of anger as a presenting complaint in outpatient medical settings.
AB  - OBJECTIVE: This study examined the diagnostic patterns for individuals presenting
      with a complaint of anger. METHODS: The study examined the rates of psychiatric
      diagnoses in a nationally representative sample of visits (N=1,005,628) to
      outpatient medical settings by adults who presented with a complaint of anger.
      Data were from the National Ambulatory Medical Care Survey and the National
      Hospital Ambulatory Medical Care Survey from 1998-2008. RESULTS: Anger accounted
      for .14% (N=1,146) of the presenting complaints among all adults and was
      associated with being uninsured, Medicaid enrollment, Caucasian race, male
      gender, and younger age. Eighty-four percent of visits with an anger complaint
      included a psychiatric diagnosis, with 44% of diagnoses characterized as "not
      otherwise specified." CONCLUSIONS: Individuals who presented with a complaint of
      anger received a range of conventional mental health diagnoses. These findings
      suggested a pattern of diagnosis of a presenting complaint of anger that may
      encourage inadequate or improper treatment.

PMID- 24026840
TI  - Training peer specialists in cognitive therapy strategies for recovery.

PMID- 24026839
TI  - Factors influencing service use among homeless youths with co-occurring
      disorders.
AB  - OBJECTIVE: Given high rates of co-occurring mental and substance use disorders
      among homeless youths and poorly understood facilitators of and barriers to
      service use, this study explored factors influencing service use among homeless
      youths with co-occurring disorders. METHODS: Focus groups were conducted with 23
      youths age 18 to 26 with co-occurring disorders. Group discussion was audio
      recorded and transcribed verbatim, and transcripts were examined with thematic
      content analysis. RESULTS: The factors identified as influencing service use were
      grouped into three broad categories: individual (motivation, support, and
      therapeutic relationship), program (flexibility and comprehensiveness of services
      and availability of harm reduction services), and systemic (stigma and
      accessibility). CONCLUSIONS: Multilevel factors appear to influence service use
      among homeless youths with co-occurring disorders. Given the lack of evidence to
      support specific treatments in this population, these findings may be used to
      guide the development of thoughtfully designed interventions to engage homeless
      youths with co-occurring disorders.

PMID- 24026841
TI  - Integrating mental health services for mothers of children with autism.

PMID- 24026842
TI  - Serious mental illness and weight management interventions.

PMID- 24026843
TI  - Food insecurity among adults with severe mental illness.

PMID- 24026844
TI  - A team intervention for first-episode psychosis in Japan.

PMID- 24026845
TI  - Ethnicity and service engagement among involuntary patients.

PMID- 24026846
TI  - Medication adherence among patients with comorbid diabetes.

PMID- 24026848
TI  - An open conformation determined by a structural switch for 2A protease from
      coxsackievirus A16.
AB  - Coxsackievirus A16 belongs to the family Picornaviridae, and is a major agent of
      hand-foot-and-mouth disease that infects mostly children, and to date no vaccines
      or antiviral therapies are available. 2A protease of enterovirus is a
      nonstructural protein and possesses both self-cleavage activity and the ability
      to cleave the eukaryotic translation initiation factor 4G. Here we present the
      crystal structure of coxsackievirus A16 2A protease, which interestingly forms
      hexamers in crystal as well as in solution. This structure shows an open
      conformation, with its active site accessible, ready for substrate binding and
      cleavage activity. In conjunction with a previously reported "closed" state
      structure of human rhinovirus 2, we were able to develop a detailed hypothesis
      for the conformational conversion triggered by two "switcher" residues Glu88 and
      Tyr89 located within the bll2-cII loop. Substrate recognition assays revealed
      that amino acid residues P1', P2 and P4 are essential for substrate specificity,
      which was verified by our substrate binding model. In addition, we compared the
      in vitro cleavage efficiency of 2A proteases from coxsackievirus A16 and
      enterovirus 71 upon the same substrates by fluorescence resonance energy transfer
      (FRET), and observed higher protease activity of enterovirus 71 compared to that
      of coxsackievirus A16. In conclusion, our study shows an open conformation of
      coxsackievirus A16 2A protease and the underlying mechanisms for conformational
      conversion and substrate specificity. These new insights should facilitate the
      future rational design of efficient 2A protease inhibitors.

PMID- 24026849
TI  - Pseudoxanthoma elasticum and statin prophylaxis.

PMID- 24026850
TI  - Exercise for depression.
AB  - BACKGROUND: Depression is a common and important cause of morbidity and mortality
      worldwide. Depression is commonly treated with antidepressants and/or
      psychological therapy, but some people may prefer alternative approaches such as
      exercise. There are a number of theoretical reasons why exercise may improve
      depression. This is an update of an earlier review first published in 2009.
      OBJECTIVES: To determine the effectiveness of exercise in the treatment of
      depression in adults compared with no treatment or a comparator intervention.
      SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Review
      Group's Controlled Trials Register (CCDANCTR) to 13 July 2012. This register
      includes relevant randomised controlled trials from the following bibliographic
      databases: The Cochrane Library (all years); MEDLINE (1950 to date); EMBASE (1974
      to date) and PsycINFO (1967 to date). We also searched www.controlled-trials.com,
      ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform.
      No date or language restrictions were applied to the search.We conducted an
      additional search of the CCDANCTR up to 1st March 2013 and any potentially
      eligible trials not already included are listed as 'awaiting classification.'
      SELECTION CRITERIA: Randomised controlled trials in which exercise (defined
      according to American College of Sports Medicine criteria) was compared to
      standard treatment, no treatment or a placebo treatment, pharmacological
      treatment, psychological treatment or other active treatment in adults (aged 18
      and over) with depression, as defined by trial authors. We included cluster
      trials and those that randomised individuals. We excluded trials of postnatal
      depression. DATA COLLECTION AND ANALYSIS: Two review authors extracted data on
      primary and secondary outcomes at the end of the trial and end of follow-up (if
      available). We calculated effect sizes for each trial using Hedges' g method and
      a standardised mean difference (SMD) for the overall pooled effect, using a
      random-effects model risk ratio for dichotomous data. Where trials used a number
      of different tools to assess depression, we included the main outcome measure
      only in the meta-analysis. Where trials provided several 'doses' of exercise, we
      used data from the biggest 'dose' of exercise, and performed sensitivity analyses
      using the lower 'dose'. We performed subgroup analyses to explore the influence
      of method of diagnosis of depression (diagnostic interview or cut-off point on
      scale), intensity of exercise and the number of sessions of exercise on effect
      sizes. Two authors performed the 'Risk of bias' assessments. Our sensitivity
      analyses explored the influence of study quality on outcome. MAIN RESULTS: Thirty
      nine trials (2326 participants) fulfilled our inclusion criteria, of which 37
      provided data for meta-analyses. There were multiple sources of bias in many of
      the trials; randomisation was adequately concealed in 14 studies, 15 used
      intention-to-treat analyses and 12 used blinded outcome assessors.For the 35
      trials (1356 participants) comparing exercise with no treatment or a control
      intervention, the pooled SMD for the primary outcome of depression at the end of
      treatment was -0.62 (95% confidence interval (CI) -0.81 to -0.42), indicating a
      moderate clinical effect. There was moderate heterogeneity (I2 = 63%).When we
      included only the six trials (464 participants) with adequate allocation
      concealment, intention-to-treat analysis and blinded outcome assessment, the
      pooled SMD for this outcome was not statistically significant (-0.18, 95% CI 
      0.47 to 0.11). Pooled data from the eight trials (377 participants) providing
      long-term follow-up data on mood found a small effect in favour of exercise (SMD 
      0.33, 95% CI -0.63 to -0.03).Twenty-nine trials reported acceptability of
      treatment, three trials reported quality of life, none reported cost, and six
      reported adverse events.For acceptability of treatment (assessed by number of
      drop-outs during the intervention), the risk ratio was 1.00 (95% CI 0.97 to
      1.04).Seven trials compared exercise with psychological therapy (189
      participants), and found no significant difference (SMD -0.03, 95% CI -0.32 to
      0.26). Four trials (n = 300) compared exercise with pharmacological treatment and
      found no significant difference (SMD -0.11, -0.34, 0.12). One trial (n = 18)
      reported that exercise was more effective than bright light therapy (MD -6.40,
      95% CI -10.20 to -2.60).For each trial that was included, two authors
      independently assessed for sources of bias in accordance with the Cochrane
      Collaboration 'Risk of bias' tool. In exercise trials, there are inherent
      difficulties in blinding both those receiving the intervention and those
      delivering the intervention. Many trials used participant self-report rating
      scales as a method for post-intervention analysis, which also has the potential
      to bias findings. AUTHORS' CONCLUSIONS: Exercise is moderately more effective
      than a control intervention for reducing symptoms of depression, but analysis of
      methodologically robust trials only shows a smaller effect in favour of exercise.
      When compared to psychological or pharmacological therapies, exercise appears to
      be no more effective, though this conclusion is based on a few small trials.

PMID- 24026851
TI  - A prospective comparison of intestinal sonography and abdominal radiographs in a
      neonatal intensive care unit.
AB  - BACKGROUND: No study reported in the literature comprehensively compares findings
      on neonatal abdominal radiographs with sonography. OBJECTIVE: To compare the
      findings on abdominal radiographs and sonograms in infants in intensive care, to
      better understand how the various intestinal gas patterns on radiographs relate
      to the spectrum of appearances on sonography and, second, to evaluate the ability
      of sonography to differentiate necrotizing enterocolitis from other intestinal
      pathology. MATERIALS AND METHODS: We prospectively evaluated sonograms and
      radiographs, blinded to the other modality and to clinical information. Patients'
      charts were reviewed by a third blinded reader and used as a reference standard
      for diagnosis. We made associations between sonographic findings, radiographic
      intestinal gas patterns and clinical diagnoses. RESULTS: We included 75 infants
      with gestational ages between 23 weeks and 41 weeks. Sonographic abnormalities
      were present in infants with all radiographic intestinal gas patterns, including
      normal patterns. We only saw absent intestinal perfusion and fluid collections on
      sonography (suggesting intestinal necrosis and sealed perforation) in infants
      with intestinal dilatation with elongation on radiographs. Separation of
      intestinal loops on radiographs was most commonly caused by reasons other than
      intestinal wall thickening. Increased intestinal echogenicity or free fluid with
      echoes on sonography correlated with a diagnosis of necrotizing enterocolitis,
      whereas anechoic free fluid correlated with absence of necrotizing enterocolitis.
      CONCLUSION: Sonography is complementary to radiographs in infants with suspected
      intestinal pathology, with a spectrum of appearances seen on each modality. Some
      sonographic findings either strongly suggest necrotizing enterocolitis or supply
      evidence against this diagnosis.

PMID- 24026853
TI  - Second primary non-small-cell lung cancer: implications of the new adenocarcinoma
      classification in the challenging decision of the best surgical strategy.

PMID- 24026852
TI  - Ultrasound demonstration of testicular microlithiasis in pediatric patients: is
      there an association with testicular germ cell tumors?
AB  - BACKGROUND: There is suggestion that testicular microlithiasis predicts risk of
      testicular malignancy, especially testicular germ cell tumors. This association
      remains uncertain. OBJECTIVE: We retrospectively reviewed testicular germ cell
      tumor occurrence in patients with testicular microlithiasis to assess this
      association and determined the prevalence of testicular microlithiasis in
      symptomatic boys. MATERIALS AND METHODS: This study was IRB and HIPAA compliant.
      Two-thousand six-hundred twenty-five testicular US exams performed on 2,266
      children (younger than 19 years of age) in our institution from 2000 through 2011
      were reviewed for presence of testicular microlithiasis and masses. Testicular
      microlithiasis was defined as presence of five or more testicular
      microcalcifications on a single US image. Incidence of testicular germ cell
      tumors was calculated in a group of patients with testicular microlithiasis and
      in a control group without testicular microlithiasis. Relative risk, odds ratio,
      90% and 95%CI were calculated. RESULTS: Eighty-seven patients out of 2,266 had
      testicular microlithiasis. One child was found to have both testicular germ cell
      tumor and testicular microlithiasis. In 2,179 children without testicular
      microlithiasis, 8 had testicular germ cell tumors. Incidence of testicular
      microlithiasis was 3.8%. Incidence of testicular germ cell tumors in testicular
      microlithiasis patients was 1.2%, and 0.38% in non-testicular microlithiasis
      patients. Relative risk of testicular germ cell tumors in testicular
      microlithiasis patients vs. non-testicular microlithiasis patients was 3.13
      (90%CI: 0.55-17.76; 95%CI: 0.40-24.76), odds ratio 3.16 (90%CI: 0.55-18.32;
      95%CI: 0.39-25.5). CONCLUSION: There is no association between testicular
      microlithiasis and testicular germ cell tumors. We had hoped to do a meta
      analysis, but only two studies had a sufficient case control group of non
      testicular microlithiasis patients.

PMID- 24026854
TI  - Management of neonatal Ebstein's anomaly: towards a rational approach?

PMID- 24026855
TI  - Cold ischaemic time and time after transplantation alter segmental myocardial
      velocities after heart transplantation.
AB  - OBJECTIVES: The aim of this study was to investigate changes in segmental, three
      directional left ventricular (LV) velocities in patients after heart
      transplantation (Tx). METHODS: Magnetic resonance tissue phase mapping was used
      to assess myocardial velocities in patients after Tx (n = 27) with normal LV
      ejection fraction (63 +/- 5%) and those without signs of rejection. Regional wall
      motion and dyssynchrony were analysed in relation to cold ischaemic time (150 +/-
      57 min, median = 154 min), age of the donor heart (35 +/- 13 years, median = 29
      years), time after transplantation (32 +/- 26 months, median = 31 months) and
      global LV morphology and function. RESULTS: Segmental myocardial velocities were
      significantly altered in patients with cold ischaemic times >155 min resulting in
      an increase in peak systolic radial velocities (2 of 16 segments, P = 0.03-0.04)
      and reduced segmental diastolic long-axis velocities (5 of 16 segments, P = 0.01
      0.04). Time after transplantation (n = 8 patients <12 months after Tx vs n = 19
      >12 months) had a significant influence on systolic radial velocities (increased
      in 2 of 16 segments, P = 0.01-0.04) and diastolic long-axis velocities (reduced
      in 5 of 16 segments, P = 0.02-0.04). Correlation analysis and multiple regression
      revealed significant relationships of cold ischaemic time (R = -0.384, P =
      0.048), the donor heart's age (beta= 0.9, P = 0.01) and time from transplantation
      (beta= -0.36, P = 0.03) with long-axis diastolic dyssynchrony. CONCLUSIONS: Time
      after transplantation and cold ischaemic time strongly affect segmental systolic
      and diastolic motion in patients after Tx. The understanding of alterations in
      regional LV motion in the transplanted heart under stable conditions is essential
      in order to utilize this methodology in the future as a potentially non-invasive
      means of diagnosing transplant rejection.

PMID- 24026856
TI  - Video-assisted thoracoscopic surgery lobectomy or open lobectomy for non-small
      cell lung cancer? Minimizing selection bias in observational studies.

PMID- 24026857
TI  - Giant basal cell carcinoma of the anterior chest wall with bone invasion.
AB  - Giant basal cell carcinoma (BCC) of the chest wall is rare and poses challenges
      related to resection and reconstruction. A 69-year old man presented with giant
      BCC invading sternum. Wide resection and reconstruction with
      polymethylmethacrylate and mesh was performed. The soft tissue defect was covered
      with a pedicled omental flap and skin graft. He developed an infection requiring
      removal of the mesh construct; however, debridement and antibiotics cleared the
      infection. This case illustrates the locally aggressive nature of this disease
      and the need for tertiary-level care. 

PMID- 24026858
TI  - Characterization of the NSP4 gene of group A human rotavirus G1P[8] strains
      circulating in Sapporo, Japan from 1987 to 2000.
AB  - The genetic diversity of the NSP4 gene of rotavirus G1P[8] strains obtained in
      Sapporo was analyzed, Japan from 1987 to 2000. Sixty-four strains, which were
      distributed across the whole study period, were included. All G1P[8] NSP4 genes
      detected in this study belonged to genotype E1, which divided into at least three
      lineages. The Sapporo rotavirus G1P[8] isolates were found in each lineage. The
      mean estimated substitution rate was 1.40 * 10(-3) nucleotide substitutions per
      site per year, which was comparable to that of the G1P[8] VP7 gene. Comparison of
      the deduced NSP4 amino acid sequences showed genetic diversity at the center of
      antigenic site II, but not in the enterotoxic domain. This report represents the
      first investigation of the genetic diversity and evolution of group A rotavirus
      NSP4 genes in Asia.

PMID- 24026859
TI  - Neoadjuvant bevacizumab: surgical complications of mastectomy with and without
      reconstruction.
AB  - Neoadjuvant therapy (NAC) is commonly used in operable breast cancer. Previous
      studies have suggested a high rate of postoperative complications after NAC. We
      prospectively evaluated the surgical complications in a cohort of patients who
      underwent mastectomy following neoadjuvant adriamycin/cytoxan/taxol (AC/T) plus
      bevacizumab (bev) and compared the rate of complications to a matched cohort of
      neoadjuvant AC/T without bev. One hundred patients with HER2-negative breast
      cancer enrolled in a single-arm trial of neoadjuvant AC/T plus bev (cohort 1), 60
      of these patients underwent mastectomy and were matched with 59 patients who
      received standard neoadjuvant AC/T (cohort 2) over a similar time period in the
      same healthcare system. All patients underwent mastectomy with or without
      reconstruction. Fisher's exact tests were used to compare complication rates,
      with p < 0.05 considered significant. Patients were matched well in terms of
      demographics. The overall complication rate was 32 % in cohort 1 and 31 % in
      cohort 2 (p value = 1, Table 1). In cohort 1, 7 of 23 (30 %) patients who
      underwent immediate expander/implant reconstruction had complications, including
      2 patients who had explantation of their reconstructions. In cohort 2, 0 of 8 (0
      %) had complications (p value = 0.15). Nearly a third of patients undergoing NAC
      with AC/T with or without bev developed a postoperative complication after
      mastectomy. The use of bev was not associated with a significant increase in
      surgical complications, although this is a nonrandomized data set with a small
      sample size. As larger data sets become available with the use of neoadjuvant
      bevacizumab with mastectomy, further refinement may be necessary. 

PMID- 24026860
TI  - Role of maximum standardized uptake value in fluorodeoxyglucose positron emission
      tomography/computed tomography predicts malignancy grade and prognosis of
      operable breast cancer: a multi-institute study.
AB  - The malignant biological behavior of breast cancer remains obscure on diagnostic
      images, although understanding the grade of such malignancy is important for
      selecting appropriate treatment. Therefore, malignancy grades in operable breast
      cancer were evaluated using positron emission tomography/computed tomography
      (PET/CT) in a multicenter setting. We prospectively examined the features and
      prognosis of 344 patients (mean age +/- SD: 58.0 +/- 12.5 years) with clinical
      stages I-III breast cancer, who underwent surgical intervention without induction
      therapy between January 2006 and December 2011. Maximum standardized uptake
      values (maxSUV) obtained from whole-body fluorodeoxyglucose-PET/CT immediately
      before surgery were assessed to predict the malignant aggressiveness of tumors
      including the recurrence-free survival of the patients. Variations in maxSUV
      among institutions, which are limitations of PET assessments in multicenter
      studies, were adjusted using a phantom study. The median follow up period was 52
      months. The patients were divided into groups according to cut-off maxSUV (<=3.0
      vs. >3.0) values established from receiver operating characteristic analysis of
      recurrence (area under the curve = 0.713). A higher maxSUV was significantly
      associated with a higher T-factor (p < 0.0001), N-factor (p = 0.0049), nuclear
      grade (p < 0.0001), negative for estrogen (p = 0.0309), and progesterone
      receptors (p = 0.0063), positive for human epidermal growth factor receptor 2 (p
      = 0.0012), lymph node metastasis (p = 0.0128), and vascular invasion (p =
      0.0110). Multivariate analysis using Cox proportional hazard regression model
      revealed high maxSUV and negative estrogen receptor status as significantly
      prognostic factors (p = 0.033 and p = 0.004, respectively). This study
      demonstrated that maxSUV on PET/CT as well as estrogen receptor status is useful
      to predict malignancy grades and the prognosis of patients with breast cancer.

PMID- 24026861
TI  - BRCA1 promoter methylation is a marker of better response to anthracycline-based
      therapy in sporadic TNBC.
AB  - The aim of the current study was to investigate the role of BRCA1 gene
      aberrations in sporadic triple-negative breast cancer (TNBC) and its impact on
      anthracycline-based therapy. BRCA1 promoter methylation was analyzed in 70 TNBC
      and compared with the clinical and pathologic characteristics. As a control
      group, we used 70 patients with non-TNBC. BRCA1 promoter methylation was observed
      in 65.2 % of patients and was similar in both groups. BRCA1 promoter methylation
      was associated with decreased intensity of BRCA1 protein expression (P = 0.002)
      and significant increase of median disease-free survival (DFS) of TNBC patients
      receiving adjuvant anthracycline-based chemotherapy (P = 0.001). Multivariate
      analysis revealed that BRCA1 promoter methylation remains a favorable factor in
      regard to DFS (HR 0.224; 95 % CI 0.092-0.546, P = 0.001) in TNBC after adjustment
      for other prognostic factors. In contrast, in non-TNBC, BRCA1 promoter
      methylation was not associated with any clinical and pathologic parameters. BRCA1
      promoter methylation is a common mechanism of BRCA1 gene aberration in sporadic
      breast cancer and is predictive for better response to anthracycline-based
      therapies.

PMID- 24026862
TI  - Smoking increases oral HPV persistence among men: 7-year follow-up study.
AB  - Persistent high-risk human papillomavirus (HR-HPV) infection is the key event in
      the progression of HPV lesions, and more data are urgently needed on asymptomatic
      oral HPV infections in men. Asymptomatic fathers-to-be (n = 131, mean age 28.9
      years) were enrolled in the cohort, sampled by serial oral scrapings at baseline
      and at 2-month, 6-month, 12-month, 24-month, 36-month, and 7-year follow-up
      visits to accomplish persistent and cleared HPV infections. HPV genotyping was
      performed using nested PCR and Multimetrix(r) assay. Covariates of persistent and
      cleared oral HPV infections were analysed using generalised estimating equation
      (GEE) and Poisson regression. Altogether, 17 HPV genotypes were detected in male
      oral mucosa point prevalence, varying from 15.1 % to 31.1 %. Genotype-specific
      HPV persistence was detected in 18/129 men the mean persistence time ranging from
      6.0 to 30.7 months. History of genital warts decreased (p = 0.0001; OR = 0.41, 95
      % CI 0.33-0.51) and smoking increased (p = 0.033, OR = 1.92, 95 % CI 1.05-3.50)
      the risk of persistent species 7/9 HPV infections. Of the 74 HPV-positive men,
      71.6 % cleared their infection actuarial and crude clearance times, varying
      between 1.4 and 79.6 months. No independent predictors were identified for
      species 7/9 clearance. At the last follow-up-visit, 50.1 % of the fathers had
      oral mucosal changes, correlating only with smoking (p = 0.046). To conclude,
      most of the persisting oral infections in males were caused by HPV16. Smoking
      increased while previous genital warts decreased oral HR-HPV persistence. No
      predictors of HR-HPV clearance were disclosed.

PMID- 24026866
TI  - SEOM clinical guidelines for the adjuvant treatment of colorectal cancer 2013.
AB  - Colorectal cancer is one of the most important causes of cancer mortality
      worldwide. This article reviews the available evidence for optimum management of
      stage II and III colorectal cancer, with respect to staging, surgical and
      adjuvant neoadjuvant treatment. 

PMID- 24026863
TI  - Clinical and economic burden of invasive fungal diseases in Europe: focus on pre
      emptive and empirical treatment of Aspergillus and Candida species.
AB  - Invasive fungal diseases (IFDs) have been widely studied in recent years, largely
      because of the increasing population at risk. Aspergillus and Candida species
      remain the most common causes of IFDs, but other fungi are emerging. The early
      and accurate diagnosis of IFD is critical to outcome and the optimisation of
      treatment. Rapid diagnostic methods and new antifungal therapies have advanced
      disease management in recent years. Strategies for the prevention and treatment
      of IFDs include prophylaxis, and empirical and pre-emptive therapy. Here, we
      review the available primary literature on the clinical and economic burden of
      IFDs in Europe from 2000 to early 2011, with a focus on the value and outcomes of
      different approaches. 

PMID- 24026867
TI  - Fluorimetric analysis of the binding characteristics of 5-enolpyruvylshikimate-3
      phosphate synthase with substrates in Dunaliella salina.
AB  - A general model of the catalytic mechanism for 5-enolpyruvylshikimate-3-phosphate
      synthase (EPSPs) has already been proposed. But whether shikimate-3-phosphate
      (S3P) alone can cause EPSPs' conformation changes, and whether the binding site
      of phosphoenolpyruvate (PEP) and glyphosate is the same are still in debate. In
      this paper, DsaroA gene amplified and cloned from Dunaliella salina (our
      laboratory's early study) was used for DsEPSPs expression and purification. Then
      the DsEPSP conformation changes as it bind with different substrates were
      detected by fluorimetry. The results show that we obtained the DsEPSPs by
      prokaryotic expression and purification, and the S3P binding with DsEPSPs alone
      cannot cause DsEPSPs to form "close" conformation directly. However, when S3P
      exits, DsEPSPs did have a trend to change to the "close" conformation. Then the
      "close" conformation can be formed completely with the addition of
      phosphoenolpyruvate (PEP) or glyphosate. The inorganic phosphorus can help S3P to
      induce two domains of DsEPSPs to form "close" conformation. Besides, when DsEPSPs
      binds with S3P, in 295 nm, only the intensity of emission peak decreases,
      however, in 280 nm, not only the peak intensity reduces but also the blue-shift
      phenomenon takes place. The reason for blue-shift phenomenon was the distribution
      of aromatic amino acids in EPSPs. EPSPs is a good target for novel antibiotics
      and herbicides, because of shikimic acid pathway is only present in plants and
      microorganisms, completely absent in mammals, fish, birds, reptiles, and insects.
      The results demonstrate that the binding of substrates to EPSPs causes a
      conformational change from an open form to a closed form, that might be important
      for designing of novel antimicrobial and herbicidal agents that block closure of
      the enzyme. 

PMID- 24026868
TI  - Physical disability in the elderly with diabetes: epidemiology and mechanisms.
AB  - Diabetes mellitus is a common chronic condition worldwide, especially in the
      elderly population. Several epidemiologic studies in the last 2 years have
      consistently associated diabetes with physical disability, a condition that may
      profoundly affect the quality of life of older people. Although in older people
      with diabetes, the pathogenesis of functional limitation and disability has not
      been completely elucidated, it is certainly complex and involves multiple
      potential pathways. In this narrative review, we described the most recent
      epidemiologic and clinical evidence supporting the association between diabetes
      and impaired physical function in older persons focusing on emerging biological
      mechanisms explaining the excess risk of disability associated with diabetes. 

PMID- 24026870
TI  - Copper-catalyzed cyclic oxytrifluoromethylation of 2,3-allenoic acids to
      trifluoromethylated butenolides.
AB  - Rounding up: An efficient copper-catalyzed cyclic oxytrifluoromethylation of 2,3
      allenoic acids under mild conditions, providing a straightforward approach to
      beta-trifluoromethylated butenolides has been developed. Based on the successful
      trapping of a CF3 radical intermediate, a mechanism involving pi-allylic
      copper(III) or radical intermediate is proposed. 

PMID- 24026872
TI  - [Editorial on ophthalmology during national socialism - the appointment procedure
      in Greifswald 1938].

PMID- 24026871
TI  - Subconjunctival bevacizumab in the impending recurrent pterygia.
AB  - The aim of this study is to evaluate the efficacy and safety of subconjunctival
      bevacizumab injection(s) in the treatment of impending recurrent pterygia. Twenty
      three eyes of 23 patients who developed impending recurrence after pterygium
      surgery with conjunctival autografting and were treated with subconjunctival
      bevacizumab injection(s) (2.5 mg/0.1 mL) were included in the study. Anterior
      segment photographs were taken prior to and at 1 week, 1, 3 and 6 months after
      the injection, and at the end of the follow-up period. Image analysis was
      performed using an image processing and analysis software program. Recurrence
      rate and complications were recorded. The mean age and follow-up time of the
      patients were 51.2 +/- 6.2 (31-60 years) and 16.8 +/- 3.1 (12-22 months),
      respectively. The average number of injections was 2 +/- 0.78 (1-3). Sixteen eyes
      required re-injection (two injections in nine eyes, three injections in seven
      eyes), due to progression of vascularization. There were significant differences
      between size percentage of lesions before injection and at 1 week, 1, 3 and 6
      months after the injection (p < 0.05 for all). Corneal recurrence developed in
      only one patient and no ocular or systemic side-effects of bevacizumab were
      observed. Repeated injections of bevacizumab may help to prevent the high
      recurrence rate of residual impending pterygium, due to its adjuvant role in
      decreasing lesion size, especially in the first year after surgery.

PMID- 24026873
TI  - [Fundus autofluorescence in dry AMD - impact on disease progression].
AB  - BACKGROUND AND PURPOSE: Fundus autofluorescence is a novel technique that gives
      us information about the RPE cells by evaluating the distribution of lipofuscin
      in the retina. The purpose of our study was to evaluate the diagnostic abilities
      of OCT, RTVue and fundus autofluorescence in predicting the progression of dry
      AMD. MATERIAL AND METHODS: In our study 37 dry AMD patients were enrolled: 22 of
      them with druses and 15 with developed geographic atrophy. They all underwent
      complete ophthalmological examinations including OCT and autofluorescence. We
      used the RTVue OCT programmes HD line, Cross line, EMM5 and EMM5 progression in
      all cases. The autofluorescence was recorded with the help of the Canon CX1
      fundus camera. RESULTS: OCT images in the AMD patients with dry AMD and large
      druses showed typical undulations in the RPE/choroid line and occasionally
      drusenoid detachment of the RPE. Autofluorescence showed different patterns. The
      confluent reticular autofluorescence was associated with the development of
      neovascular membranes. In geographic atrophy patient OCTs showed diminished
      retinal thickness measured with EMM5. On autofluorescence the findings at the
      border zone atrophic/normal retina were of particular importance. The diffuse
      increased autofluorescence in that area was considered to be a sign for further
      atrophy progression. CONCLUSION: Our results point out that OCT in combination
      with autofluorescence is important in following the progression of dry AMD.
      Pathological autofluorescence at the border of atrophic lesions is an important
      sign for disease activity. Although both OCT and autofluorescence visualise the
      changes in RPE, autofluorescence is of key importance in predicting the
      development of the disease.

PMID- 24026874
TI  - [Ophthalmology under national socialism - the appeals procedure of Greifswald
      1938].

PMID- 24026869
TI  - What the genetics of lipodystrophy can teach us about insulin resistance and
      diabetes.
AB  - Genetic lipodystrophic syndromes are rare diseases characterized by generalized
      or partial fat atrophy (lipoatrophy) associated with severe metabolic
      complications such as insulin resistance (IR), diabetes, dyslipidemia,
      nonalcoholic fatty liver disease, and ovarian hyperandrogenism. During the last
      15 years, mutations in several genes have been shown to be responsible for
      monogenic forms of lipodystrophic syndromes, of autosomal dominant or recessive
      transmission. Although the molecular basis of lipodystrophies is heterogeneous,
      most mutated genes lead to impaired adipogenesis, adipocyte lipid storage, and/or
      formation or maintenance of the adipocyte lipid droplet (LD), showing that
      primary alterations of adipose tissue (AT) can result in severe systemic
      metabolic and endocrine consequences. The reduced expandability of AT alters its
      ability to buffer excess caloric intake, leading to ectopic lipid storage that
      impairs insulin signaling and other cellular functions ("lipotoxicity"). Genetic
      studies have also pointed out the close relationships between ageing,
      inflammatory processes, lipodystrophy, and IR. 

PMID- 24026876
TI  - A cisplatin plus pirarubicin-based JPLT2 chemotherapy for hepatoblastoma:
      experience and future of the Japanese Study Group for Pediatric Liver Tumor
      (JPLT).
AB  - INTRODUCTION: The Japanese Study Group for Pediatric Liver Tumor (JPLT) has
      conducted cooperative treatment studies on hepatoblastoma (HBL) since 1991. The
      JPLT2 protocol was launched in 1999 to evaluate the efficacy of
      cisplatin/pirarubicin (CITA) under risk stratification. European and North
      American groups showed the improvement of HBL patients by pre- and postoperative
      chemotherapeutic regimens. Therefore, we evaluated the results of JPLT study and
      considered the future aspect of JPLT. METHODS: A total of 389 children with
      malignant hepatic tumors were enrolled in JPLT-2 until 2010. Data from 331 HBL
      cases were analyzed. RESULTS AND DICUSSION: Of the 331 patients enrolled, their 5
      year overall survival and event-free survival rates were 83.3 and 68.0%,
      respectively. While outcomes of standard-risk cases (tumors involving 3 or fewer
      sectors of the liver) were excellent, those of high-risk cases (tumors involving
      4 sectors of the liver or with distant metastases) remained poor. For 26 high
      risk or relapse/refractory HBL cases, high-dose chemotherapy (HDC) with stem cell
      transplantation (SCT) was carried out. Among them, 6 of 12 relapse or refractory
      cases died. Compared with other regimens, the CITA regimen achieved similar or
      superior rates of survival among children with standard-risk HBL, while HDC with
      SCT was not effective in patients with high-risk HBL. Presently, a global
      Children's Hepatic Tumor International Consortium (CHIC) project is ongoing, with
      a focus on international cooperation and risk stratification in the field of rare
      liver cancers in children. More promising strategies, including liver
      transplantation and new targeting drugs under global risk stratification, are
      being proposed.

PMID- 24026875
TI  - Differential pathogenicity among Tomato leaf curl Gujarat virus isolates from
      India.
AB  - Tomato leaf curl Gujarat virus (ToLCGV) has been identified as one of the most
      destructive pathogens causing tomato leaf curl disease (ToLCD) in India. In the
      tomato growing regions of Dhanbad and Ramgarh, plants bearing severe symptoms of
      ToLCD such as leaf curling, leaf crinkling, yellowing and leaf rolling was
      observed in the farmer fields. The association of begomovirus in these samples
      was confirmed by PCR and the causal viruses were identified as the isolates of
      ToLCGV. However, association of cognate DNA B component could not be ascertained
      from these samples. Indeed, like other Old World begomoviruses, the present
      ToLCGV isolates were found to be associated with a particular betasatellite,
      Tomato yellow leaf curl Thailand betasatellite (TYLCTHB). Although DNA A of both
      ToLCGV isolates could alone infect tomato inducing systemic symptoms, the
      difference in virulence was observed. Co-inoculation of TYLCTHB reduced the
      incubation period without influencing the accumulation of helper virus DNA and
      hence, differential pathogenesis among ToLCGV isolates was governed by the helper
      component rather than betasatellite. ToLCGV infection with DNA B increases the
      accumulation of DNA A component of Dhanbad isolate but not of Ramgarh isolate.
      Results indicated that the begomovirus identified from Ramgarh sample was a mild
      strain of ToLCGV. 

PMID- 24026877
TI  - Responses of grape berry anthocyanin and titratable acidity to the projected
      climate change across the Western Australian wine regions.
AB  - More than a century of observations has established that climate influences grape
      berry composition. Accordingly, the projected global climate change is expected
      to impact on grape berry composition although the magnitude and direction of
      impact at regional and subregional scales are not fully known. The aim of this
      study was to assess potential impacts of climate change on levels of berry
      anthocyanin and titratable acidity (TA) of the major grapevine varieties grown
      across all of the Western Australian (WA) wine regions. Grape berry anthocyanin
      and TA responses across all WA wine regions were projected for 2030, 2050 and
      2070 by utilising empirical models that link these berry attributes and climate
      data downscaled (to ~5 km resolution) from the csiro_mk3_5 and miroc3_2_medres
      global climate model outputs under IPCC SRES A2 emissions scenario. Due to the
      dependence of berry composition on maturity, climate impacts on anthocyanin and
      TA levels were assessed at a common maturity of 22  degrees Brix total soluble
      solids (TSS), which necessitated the determination of when this maturity will be
      reached for each variety, region and warming scenario, and future period. The
      results indicate that both anthocyanin and TA levels will be affected negatively
      by a warming climate, but the magnitude of the impacts will differ between
      varieties and wine regions. Compared to 1990 levels, median anthocyanins
      concentrations are projected to decrease, depending on global climate model, by
      up to 3-12 % and 9-33 % for the northern wine regions by 2030 and 2070,
      respectively while 2-18 % reductions are projected in the southern wine regions
      for the same time periods. Patterns of reductions in the median Shiraz berry
      anthocyanin concentrations are similar to that of Cabernet Sauvignon; however,
      the magnitude is lower (up to 9-18 % in southern and northern wine regions
      respectively by 2070). Similarly, uneven declines in TA levels are projected
      across the study regions. The largest reductions in median TA are likely to occur
      in the present day warmer wine regions, up to 40 % for Chardonnay followed by 15
      % and 12 % for Shiraz and Cabernet Sauvignon, respectively, by 2070 under the
      high warming projection (csiro_mk3_5). It is concluded that, under existing
      management practices, some of the key grape attributes that are integral to
      premium wine production will be affected negatively by a warming climate, but the
      magnitudes of the impacts vary across the established wine regions, varieties,
      the magnitude of warming and future periods considered.

PMID- 24026878
TI  - Endovascular treatment of the common femoral artery for limb ischemia.
AB  - OBJECTIVE: To determine the short- and mid-term outcomes of percutaneous
      endovascular common femoral artery (CFA) revascularization (eCFR) of the CFA.
      METHODS: A review of patients who underwent eCFR for limb ischemia between 2006
      and 2012 was performed. Limb salvage, patient survival, survival free from
      reintervention, and survival free from amputation rates were determined. Median
      (range) follow-up was 28 (1-71) months. RESULTS: In all, 115 patients underwent
      121 eCFR for CFA occlusion (n = 13) or stenosis (n = 108); 109 (90%) were
      technically successful and 7 (6%) had significant perioperative complications;
      access site hematoma (n = 2) and thromboembolism (n = 5). Thirty-day mortality
      and amputation rates were 2.5% and 0.8%, respectively. The 1- and 3-year limb
      salvage rates were 97% and 97%, respectively. The 1- and 3-year survival free
      from reintervention rates were 77% and 57%, respectively. The 1- and 3-year
      survival free from amputation rates were 84% and 70%, respectively. CONCLUSION:
      These novel data demonstrate that eCFR is a durable treatment for patients with
      limb ischemia associated with CFA disease.

PMID- 24026879
TI  - Synthesis, properties, and remarkable 2 D Self-Assembly at the Liquid/Solid
      interface of a series of triskele-shaped 5,11,17-triazatrinaphthylenes (TrisK).
AB  - A series of 5,11,17-triazatrinaphthylene (TrisK) derivatives, large disk-like pi
      conjugated molecules with C3h symmetry, has been synthesised by following an
      optimised synthetic pathway. The synthesis was performed by a four-step protocol
      based on the N-arylation of 1,3,5-tribromobenzene with appropriate anthranilate
      derivatives. This strategy permits the generation of either chlorinated (TrisK-Cl
      OCn) or non-chlorinated (TrisK-H-OCn) alkoxy-substituted derivatives (OCn H2n+1
      with n=3, 10, 12 and 16), thus providing additional versatility in the control of
      the structure-property relationships. The electronic properties of the various
      TrisK compounds have been characterised in solution by absorption and emission
      spectroscopies as well as cyclic voltammetry. The crystal structure of 2,8,14
      propyloxy-5,11,17-triazatrinaphthylene TrisK-H-OC3 has been determined by X-ray
      diffraction analysis, which revealed the presence of stabilising weak
      intermolecular H bonds. Scanning tunnelling microscopy (STM) at the liquid/solid
      interface has revealed the remarkable 2D self-assembling properties of the TrisK
      compounds. In particular, it has shown that TrisK-H-OC12 forms three concomitant
      self-organised 2D phases with different row-packing arrangements. This 2D
      polymorphism arises from slow ordering due to the presence of three long
      dodecyloxy chains on the molecular backbone. Individual molecules can be imaged
      with spectacular intramolecular resolution, thus providing the possibility of
      correlating the STM features with the calculated charge density distribution. 

PMID- 24026881
TI  - ERBP Guideline on the Management and Evaluation of the Kidney Donor and
      Recipient.

PMID- 24026882
TI  - TRAF6 promoted the metastasis of esophageal squamous cell carcinoma.
AB  - Esophageal cancer is one of the most aggressive malignancies and has been ranked
      as the sixth leading cause of cancer-related death in the world. It is very
      urgent to find new therapeutic targets. Although tumor necrosis factor receptor
      associated factor 6 (TRAF6) was initially identified as an adaptor for NF-kappaB
      signaling, recently it has been found to be involved in cancer by modulating
      various signaling pathways. In the previous study, we have found that TRAF6
      promoted the growth of esophageal squamous cell carcinoma (ESCC) cell in vitro
      and in vivo. However, the effects of TRAF6 on the migration and metastasis of
      ESCC cells are poorly understood. Here, we found that TRAF6 promoted migration
      and metastasis of ESCC cells through modulating Ras signaling. Overexpression of
      TRAF6 promoted the migration of ESCC cells and immortalized esophageal epithelial
      cells, while knock down the expression of TRAF6 inhibited the migration and
      metastasis of ESCC cells in vitro and in vivo. Mechanically, TRAF6 binds Ras with
      its N-terminal and activated Ras signaling. Taken together, TRAF6 played an
      important role in the metastasis of ESCC and might be a promising therapeutic
      target. 

PMID- 24026883
TI  - Cytokines in osteoblast-conditioned medium promote the migration of breast cancer
      cells.
AB  - Bone is one of the most common metastatic sites for breast cancer. In this study,
      we observed a promoting effect of osteoblast-conditioned medium (OCM) on the
      migration of MCF-7, a noninvasive cell line of breast cancer cells. Cytokine
      antibody array was used to compare the cytokines of OCM with the conditioned
      medium of non-differentiated osteoblast cells, which consequently revealed
      factors related to migration, such as IL8, IL6, CSF2 (G-CSF), CSF3 (GM-CSF), and
      TNFRSF11B (osteoprotegerin). The expression of genes related to migration was
      also estimated with a PCR array, which showed that 9 genes were upregulated and
      26 genes downregulated. Moreover, activated p38, ERK, and AKT pathways were found
      in the OCM treatment group. This finding indicated the migration ability of
      breast cancer cells, which move toward the bone depending on the presence of
      specific cytokines in its surrounding microenvironment. 

PMID- 24026885
TI  - Association of polymorphisms in interleukin-18 and interleukin-28B genes with
      outcomes of hepatitis B virus infections: a meta-analysis.
AB  - Several polymorphisms in the interleukin-18 (IL-18) and nterleukin-28B (IL-28B)
      genes have been reported to influence hepatitis B virus (HBV) infection. However,
      the published findings have been conflicting. We conducted meta-analyses of
      randomized, controlled trials to address the association of IL-18 or IL-28B
      polymorphisms and the outcomes of HBV infection. Weipu, Wanfang, CNKI, MEDLINE,
      PubMed, EMBASE, and Cochrane Library databases were employed to search for
      citations using the MeSH terms as "interleukin-18"/"interleukin-28B" AND "HBV"
      AND "gene" AND "polymorphism" without any restriction in language and publication
      year. Meta-analysis was conducted by RevMan 5.0 software. The results showed that
      the IL28B rs8099917 AA genotype (AA vs AC + CC: odds ratio (OR) = 0.63, 95 %
      confidence interval (CI) = 0.46-0.87) was associated with a decreased risk of
      hepatocellular carcinoma (HCC). Carriage of IL28B rs12979860 CC genotype was
      associated with an increased risk for developing liver cirrhosis among patients
      with HBV infection (CC vs CT + TT: OR = 1.39, 95 % CI = 1.04-1.85). Further well
      designed large studies are warranted to confirm the mechanisms by which these are
      involved in these outcomes of HBV infection.

PMID- 24026884
TI  - The effect of IGF-I receptor blockade for human esophageal squamous cell
      carcinoma and adenocarcinoma.
AB  - Insulin-like growth factor-I receptor (IGF-IR) signaling is required for
      carcinogenicity and tumor development, and this pathway has not been well studied
      in human esophageal carcinomas. Esophageal cancer is one of the human cancers
      with the worst prognosis and has two main histologies: squamous cell carcinomas
      (ESCC) and adenocarcinoma (EAC). Previously, we have reported that detection of
      the IGF axis may be useful for the prediction of recurrence and poor prognosis of
      ESCC. We have also shown the successful therapy for several gastrointestinal
      cancers using recombinant adenoviruses expressing dominant negative IGF-IR (ad
      IGF-IR/dn). The aim of this study is to develop potential targeted therapeutics
      to IGF-IR and to assess the effect of IGF-IR blockade in both of these types of
      esophageal cancer. We determined immunohistochemical expression of IGF-IR in a
      tissue microarray. We then assessed the effect of IGF-IR blockade on signal
      transduction, proliferation, apoptosis, and motility. Ad-IGF-IR/dn, a tyrosine
      kinase inhibitor, BMS-536924, and adenovirus expressing shRNA for IGF-IR were
      used. IGF-IR expression was common in both tumor types but not in normal tissues.
      IGF-IR was detected in metastatic sites at similar levels compared to the primary
      site. IGF-IR inhibition suppressed proliferation and colony formation in both
      cancers. IGF-IR blockades up-regulated both stress- and chemotherapy-induced
      apoptosis and reduced migration. Although IGF-IR/dn blocked ligand-induced
      activation of Akt-1 mainly, BMS-536924 effectively blocked both activation of Akt
      and MAPK. The IGF axis might play a key role in tumor progression of esophageal
      carcinomas. The IGF-IR targeting strategies might thus be useful anticancer
      therapeutics for human esophageal malignancies.

PMID- 24026886
TI  - Prognostic factors of carcinoma of the ampulla of Vater after surgery.
AB  - The purpose of this study was to investigate the prognostic factors of carcinoma
      of the ampulla of Vater (CAV) after surgery. The clinicopathological factors
      related to the recurrence and prognosis of 162 CAV patients after surgical
      resection were retrospectively analyzed using univariate and multivariate
      methods. The in-hospital mortality rate was 4.32 % and the 5-year disease-free
      survival and overall survival of the 162 subjects were 55.1 and 51.7 %,
      respectively. Univariate analysis revealed that an advanced T stage (P = 0.002),
      lymph nodal metastasis (P = 0.002), poor differentiation (P = 0.006), tumor size
      (P = 0.033), tumor stage (P = 0.001), carbohydrate antigen (CA) 199 serum levels
      (P = 0.000), pancreatic invasion (P = 0.001), chemotherapy/radiation therapy (P =
      0.006), and jaundice (P = 0.012) were factors that significantly affected the
      prognosis of CAV. Multivariate analysis showed that the pancreatic invasion (P =
      0.009), lymph nodal metastasis (P = 0.009), and increased CA199 serum level (P =
      0.001) were independent risk factors of recurrence. The pancreatic invasion,
      lymph nodal metastasis, and increased CA199 serum level are key prognostic
      factors of CAV after surgery.

PMID- 24026887
TI  - G84E mutation in HOXB13 is firmly associated with prostate cancer risk: a meta
      analysis.
AB  - The rare but recurrent germline G84E mutation in HOXB13 was recently found to be
      associated with a significantly increased risk of familial prostate cancer (PCa).
      However, epidemiologic findings have been inconsistent. In an attempt to confirm
      and expand the findings that the PCa risk increased in men carrying G84E, we
      therefore performed a meta-analysis to clarify the association between the
      germline G84E mutation and PCa risk. We also aim to verify the increased PCa risk
      with respect to diagnostic age, family history, and disease aggressiveness.
      Comprehensive search of databases was carried out, and other relevant articles
      were also identified. Then, the meta-analyses were conducted according to the
      standard guidelines. A total of 11 studies with 120,167 participants were
      included on the basis of inclusion criteria. The G84E allele carrier frequencies
      ranged from 0.1 to 4.9 % in the patients with PCa, as compared with 0 to 1.4 % in
      control subjects. Men with the HOXB13 G84E variant had a 4.51-fold higher
      relative risk of PCa compared with non-carriers (95 % CI 3.28-6.20). The much
      higher risks were observed in individuals with early onset (odds ratio (OR) =
      9.73, 95 % confidence interval (CI) 6.57-14.39), more than two affected relatives
      (OR = 7.27, 95 % CI 4.02-13.15), and highly aggressive disease (OR = 5.81, 95 %
      CI 3.72-9.08). Our findings provide further evidences that the rare mutation in
      HOXB13 contributes to both hereditary and sporadic PCa risk. Despite the low G84E
      carrier rate, biological and clinical implications of the mutation in subjects
      with early onset, more than two affected relatives, and highly aggressive disease
      remain important in continued investigation.

PMID- 24026888
TI  - [Proven and new methods in the treatment of genital warts].
AB  - Anogenital warts are the most common clinical manifestation of human
      papillomavirus (HPV) infections. Although easy to recognize, asymptomatic
      anogenital warts (condylomata acuminata) may be overlooked, leading to unaware
      transmission to the sexual partner. On the other hand awareness of this sexually
      transmitted disease (STD) is largely associated with a great psychological and
      social burden, in men as well as women. Spontaneous regression of genital warts
      has been observed mostly within 2-5 years; however, persisting condylomata may
      prove refractory to all current treatment options. Because removal of the warts
      does not totally eliminate the underlying viral infection, treatment of genital
      warts can often be of long duration, of varying effectiveness and with high
      recurrence rates. Without a doubt only the patient's own immune system is capable
      of clearing HPV infections. Therefore, the solution to one of mankind's oldest
      health problems will depend on the future acceptability of HPV vaccines. 

PMID- 24026889
TI  - [Infection and sepsis prevention in prostate biopsy].
AB  - Prostate biopsy is currently the gold standard in the diagnosis of carcinoma of
      the prostate. An estimated one million prostate biopsies are performed every year
      in Europe. Worldwide the most frequent form is the transrectal prostate biopsy
      using preoperative fluoroquinolone prophylaxis. In recent years an increasing
      rate of infectious complications after prostate biopsy has been observed. The
      main causative factor is fecal fluoroquinolone-resistant bacteria. This review
      aims to present the current evidence regarding infectious complications after
      prostate biopsy and strategies to reduce symptomatic infections and urosepsis. 

PMID- 24026890
TI  - WITHDRAWN: Reduced dietary salt for the prevention of cardiovascular disease.

PMID- 24026891
TI  - Isolation, transposon mutagenesis, and characterization of the novel nicotine
      degrading strain Shinella sp. HZN7.
AB  - Nicotine is a significant toxic waste generated in tobacco manufacturing.
      Biological methods for the degradation of nicotine waste are in high demand. In
      this study, we report the identification and characterization of the novel
      nicotine-degrading strain Shinella sp. HZN7. This strain can degrade 500 mg/L
      nicotine completely within 3 h at 30  degrees C and pH values of 6.5 ~ 8.0. The
      biodegradation of nicotine by Shinella sp. HZN7 involves five intermediate
      metabolites: 6-hydroxy-nicotine (6HN), 6-hydroxy-N-methylmyosmine, 6
      hydroxypseudooxynicotine (6HPON), 6-hydroxy-3-succinoyl-pyridine (HSP), and 2,5
      dihydroxypyridine, as detected by ultraviolet spectrophotometry, HPLC, and LC-MS.
      We generated three mutants, N7-W18, N7-X5, and N7-M17, by transposon mutagenesis,
      in which the nicotine-degrading pathway terminated at 6HN, 6HPON, and HSP,
      respectively. The production of the five intermediate metabolites and their order
      in the degradation pathway were confirmed in the three mutants, indicating that
      strain HZN7 degrades nicotine via a variant of the pyridine and pyrrolidine
      pathways. The mutant gene from strain N7-X5, orf2, was cloned by self-formed
      adaptor PCR, but the nucleotide and amino acid sequence showed no similarity to
      any gene or gene product with defined function. However, orf2 disruption and
      complementation suggested that the orf2 gene is essential for the conversion of
      6HPON to HSP in strain HZN7. This is the first study to provide genetic evidence
      for this variant nicotine degradation pathway.

PMID- 24026892
TI  - Comparison of two quantitative real-time CMV-PCR tests calibrated against the 1st
      WHO international standard for viral load monitoring of renal transplant
      patients.
AB  - Cytomegalovirus (CMV) replication in organ transplant recipients is commonly
      diagnosed by quantitative PCR methods. However, there has been a poor inter
      laboratory correlation of viral load values due to the lack of an international
      reference standard. In a recent study, the COBAS(r) AmpliPrep/COBAS(r) TaqMan(r)
      (CAP/CTM) CMV test calibrated to the 1st WHO CMV standard, showed good
      reproducibility in CMV load values across multiple laboratories. Fifty-seven
      follow-up plasma specimens from 10 kidney transplant recipients with CMV
      replication were examined using the new quantitative CAP/CTM CMV test and the "in
      house" quantitative CMV real-time PCR method, also calibrated against the 1st WHO
      CMV standard for their clinical applicability for monitoring CMV load in renal
      transplant patients. By CAP/CTM CMV test 49/57 specimens were CMV-DNA positive
      compared to 44/57 by the "in-house" PCR test. The "in-house" PCR and CAP/CTM CMV
      test correlated well in monitoring individual kidney transplant patients.
      Conversion of the CMV-DNA copies to IUs made the results of the "in-house" PCR
      and CAP/CTM CMV test less uniform in analysis of the patient samples. In
      specimens of one patient, significant underquantification of CMV load with "in
      house" PCR emerged during follow-up due to a point mutation in the "in-house" PCR
      primer sequence. The CAP/CTM CMV test was found suitable for diagnosing and
      monitoring CMV replication in renal transplant patients. Multicenter studies are
      needed to provide more information of the commutability of the 1st WHO CMV
      standard and to define the clinical thresholds.

PMID- 24026894
TI  - A child with benign neonatal jitteriness and spasmus nutans.
AB  - This patient, a 26-month-old girl, developed benign neonatal jitteriness soon
      after birth that subsequently resolved at 3 months of age. At 6 months of age,
      she developed spasmus nutans with left monocular nystagmus and head shaking in a
      "no-no" pattern. Physical examination was otherwise unremarkable. Magnetic
      resonance imaging (MRI) of the brain, optic nerves, and orbits was normal. The
      spasmus nutans also gradually resolved by 18 months of age. To our knowledge, the
      co-occurrence of these 2 benign movement disorders in an individual has not
      previously been reported. The pathogenesis of benign neonatal jitteriness and
      spasmus nutans is unknown. Their co-occurrence may reflect a shared underlying
      mechanism. 

PMID- 24026893
TI  - Primary hyperparathyroidism and metabolic risk factors, impact of
      parathyroidectomy and vitamin D supplementation, and results of a randomized
      double-blind study.
AB  - BACKGROUND: Vitamin D insufficiency may increase the risk for cardio metabolic
      disturbances in patients with primary hyperparathyroidism (PHPT). OBJECTIVE: To
      analyze the vitamin D status and indices of the metabolic syndrome in PHPT
      patients and the effect of vitamin D supplementation after parathyroid
      adenomectomy (PTX). DESIGN AND METHODS: Double-blinded, randomized clinical trial
      (ClinicalTrials.gov identifier: NCT00982722) performed at Karolinska University
      Hospital, Sweden, April 2008 to November 2011. One hundred and fifty consecutive
      patients with PHPT (119 women) were randomized after PTX, 75 to oral treatment
      with calcium carbonate 1000 mg daily and 75 to calcium carbonate 1000 mg and
      cholecalciferol 1600 IU daily over 12 months. Changes in metabolic profile and
      ambulatory blood pressure (BP) were analyzed. Main outcome measures were changes
      in metabolic factors, BP, and body composition. RESULTS: The 25-hydroxyvitamin D
      (25-OH-D)-level was <50 nmol/l in 76% of the patients before PTX. After PTX,
      glucose, insulin, and IGF1 decreased, while the 25-OH-D and the IGF-binding
      protein 1 increased and remained unchanged at follow-up after study medication.
      One year of vitamin D supplementation resulted in lower parathyroid hormone (PTH)
      (40 (34-52) vs 49 (38-66) ng/l) and higher 25-OH-D (76 (65-93) vs 49 (40-62)
      nmol/l; P<0.05). Other laboratory parameters were stable compared with after PTX.
      Systolic BP decreased and total bone mineral content increased in both groups.
      CONCLUSION: Except for the lowering of the PTH level, no additive effect of
      vitamin D supplementation was seen. However, PTX proved effective in reducing
      insulin resistance.

PMID- 24026895
TI  - Effect of a single dose of propofol and lack of dextrose administration in a
      child with mitochondrial disease: a case report.
AB  - Propofol infusion syndrome is a recognized complication of prolonged propofol use
      in the pediatric population, but little is reported on other metabolic effects of
      propofol, especially in children with mitochondrial disorders. We report on a
      child with metabolic encephalopathy, lactic acidosis, and stroke-like syndrome
      who received a single dose of propofol for procedural sedation. The patient's
      initial presentation was consistent with a mild exacerbation of her underlying
      disease. She received a single dose of propofol and non-dextrose-containing
      fluids during a magnetic resonance imaging (MRI) study to rule out stroke and
      progressed to develop severe acidosis, neurologic deterioration, and
      cardiorespiratory compromise. This is the first case report of severe metabolic
      disturbances after a single dose of propofol administered for procedural sedation
      in a patient with metabolic encephalopathy, lactic acidosis, and stroke-like
      syndrome and it questions the safety of propofol and absence of dextrose
      infusions during an acute illness in patients with mitochondrial disorders. 

PMID- 24026896
TI  - Reply to correspondence.

PMID- 24026897
TI  - Trends of the effective dose distribution of occupational exposures in medical
      and research departments for KIRAMS in Republic of Korea.
AB  - This work proposes the basic reference data of occupational dose management and
      statistical dose distribution with the classification of radiation work groups
      though analysis of occupational dose distribution. Data on occupational radiation
      exposure from medical and scientific usage of radiation in Korea Institute of
      Radiological and Medical Sciences for the years 2002-11 are presented and
      evaluated with the characteristic tendency of radiation working groups. The
      results of occupational radiation exposure were measured by personal dosemeters.
      The monitored occupational exposure dose data were evaluated according to the
      average effective dose and collective dose. The most annual average effective
      dose for all occupational radiation workers was under 1 mSv. Considering the dose
      distribution of each department, most overexposure workers worked in
      radiopharmaceutical product facilities, nuclear medicine department and radiation
      oncology department. In addition, no monitored workers were found to have
      received an occupational exposure over 50 mSv in single year or 100 mSv in this
      period. Although the trend of occupational exposure was controlled <1 mSv after
      2007 and the radiation protection status was sufficient, it was consistently
      necessary to optimise and reduce the occupational radiation exposure. 

PMID- 24026898
TI  - Concentration of 3H in ground water and estimation of committed effective dose
      due to ground water ingestion in some places in the Maharashtra state, India.
AB  - The measurement of tritium in environmental samples requires highest possible
      sensitivity. In the present study, the authors have optimised the counting window
      for the analysis of (3)H in environmental samples using the recently installed
      Ultra Low Level Quantulus 1220 Liquid Scintillation Counting at BARC to improve
      the detection limit of the system. The optimised counting window corresponding to
      the highest figure of merit of 883.8 was found to be 20-162 channels. Different
      brands of packaged drinking waters were analysed to select a blank that would
      define the system background. The minimum detectable activity (MDA) achieved was
      1.5 Bq l(-1) for a total counting time of 500 min. The concentration of tritium
      in well and bore well water samples collected from the villages of Pune, villages
      located at 1.8 km from Tarapur Atomic Power Station, Kolhapur and Ratnagiri, was
      analysed. The activity concentration ranged from 0.55 to 3.66 Bq l(-1). The
      associated age-dependant dose from water ingestion in the study area was
      estimated. The effective committed dose recorded for different age classes is
      negligible compared with World Health Organization and US Environmental
      Protection Agency dose guidelines. 

PMID- 24026899
TI  - Effective dose from chest tomosynthesis in children.
AB  - Tomosynthesis (digital tomography) is a recently introduced low-dose alternative
      to CT in the evaluation of the lungs in patients with cystic fibrosis and
      pulmonary nodules. Previous studies have reported an adult effective dose of 0.12
      0.13 mSv for chest tomosynthesis. The aim of this study was to determine the
      paediatric effective dose from the dose-area-product. During a 3-y period, 38
      children with cystic fibrosis and 36 paediatric oncology patients were examined
      with chest tomosynthesis, totally 169 posteroanterior and 17 anteroposterior
      examinations (40 boys and 34 girls, mean age 13.7 y, range 7-20 y). Using
      recently reported paediatric chest tomosynthesis conversion factors (0.23-1.09
      mSv Gy cm(-2)) corrected for sex, age and energy, the mean posteroanterior
      effective dose calculated was 0.17 mSv; using the proposed simplified conversion
      factors of 0.6 (8-10 y), 0.4 (11-14 y) and 0.3 mSv Gy cm(-2) (15-19 y), the mean
      posteroanterior effective dose calculated was 0.15 mSv. As the difference in the
      calculated effective dose was minor, it is recommendable to use the simplified
      conversion factors. Using the conversion factor for adult chest tomosynthesis
      (0.26 mSv Gy cm(-2)), the mean effective dose was 0.11 mSv. Anteroposterior
      exposures had considerably higher effective dose. By using conversion factors
      adapted for children, the calculated risks from radiologic procedures will be
      more accurate. 

PMID- 24026900
TI  - Natural radioactivity levels of geothermal waters and their influence on soil and
      agricultural activities.
AB  - All over the world geothermal sources are used for different purposes. The
      contents of these waters are important to understand positive/negative effects on
      human life. In this study, natural radioactivity concentrations of geothermal
      waters were investigated to evaluate the effect on soils and agricultural
      activities. Geothermal water samples were collected from the Seferihisar
      Geothermal Region, and the radon and radium concentrations of these waters were
      analysed using a collector chamber method. Also soil samples, which are irrigated
      with geothermal waters, were collected from the surroundings of geothermal areas,
      and natural radioactivity concentrations of collected samples (U, Th and K) were
      determined using an NaI(Tl) detector system. The activity concentrations of radon
      and radium were found to be 0.6-6.0 and 0.1-1.0 Bq l(-1), respectively.
      Generally, the obtained results are not higher compared with the geothermal
      waters of the world. The activity concentrations in soils were found to be in the
      range of 3.3-120.3 Bq kg(-1) for (226)Ra (eU), 0.3-108.5 Bq kg(-1) for (232)Th
      (eTh), 116.0-850.0 Bq kg(-1) for (40)K (% K). 

PMID- 24026901
TI  - Accuracy of CT dose monitor values: a multicentric study.
AB  - Four hundred and ninety-five adult patients in 16 medical centres participated in
      this study aiming to investigate the congruence between the volume CT dose index
      (CTDIvol) monitor values and measured ones during common CT procedures, performed
      by 20 systems. Tube output CTDIair measurements were carried out on single and
      multislice scanners for any kV, slice thickness, mA and FOV combination used. The
      maximum/minimum ratio of measured CTDIvol values found to be 3.1, 3.5, 7.4, 7.5,
      4.2, 11.3 and 5.5 for head base, head cerebrum, thorax, abdomen, pelvis, cervical
      spine and lumbar spine protocols, respectively. The mean divergence between the
      measured and displayed CTDIvol values was 4.2, 3.5, -1.0, 2.7, 4.9, -3.9 and -2.8
      % for protocols as mentioned above, respectively. From the perspective of the
      number of detector rows of the scanners, the mean divergence was -6.7, -6.0, 0.8,
      -1.1, -0.4, -1.9, -5.3, 5.2 and 10.1 % for single, dual, 4, 6, 16, 24, 64, 128
      and dual source 256-slice systems, respectively. 

PMID- 24026902
TI  - Ammonia-annealed TiO2 as a negative electrode material in li-ion batteries: N
      doping or oxygen deficiency?
AB  - Improving the chemical diffusion of Li ions in anatase TiO2 is essential to
      enhance its rate capability as a negative electrode for Li-ion batteries. Ammonia
      annealing has been used to improve the rate capability of Li4 Ti5 O12 .
      Similarly, ammonia annealing improves the Li-ion storage performance of anatase
      TiO2 in terms of the stability upon cycling and the C-rate capability. In order
      to distinguish whether N doping or oxygen deficiencies, both introduced upon
      ammonia annealing, are more relevant for the observed improvement, a systematic
      electrochemical study was performed. The results suggest that the creation of
      oxygen vacancies upon ammonia annealing is the main reason for the improvement of
      the stability and C-rate capability. 

PMID- 24026903
TI  - In vitro metabolism of pyranocoumarin isomers decursin and decursinol angelate by
      liver microsomes from man and rodents.
AB  - The aim of this study is to investigate and compare the metabolic rate and
      profiles of pyranocoumarin isomers decursin and decursinol angelate using liver
      microsomes from humans and rodents, and to characterize the major metabolites of
      decursin and decursinol angelate in human liver microsomal incubations using LC
      MS/MS. First, we conducted liver microsomal incubations of decursin and
      decursinol angelate in the presence or absence of NADPH. We found that in the
      absence of NADPH, decursin was efficiently hydrolyzed to decursinol by hepatic
      esterase(s), but decursinol angelate was not. In contrast, formation of
      decursinol from decursinol angelate was mediated mainly by cytochrome P450(s).
      Second, we measured the metabolic rate of decursin and decursinol angelate in
      liver S9 fractions from mice and humans. We found that human liver S9 fractions
      metabolized both decursin and decursinol angelate more slowly than those of the
      mouse. Third, we characterized the major metabolites of decursin and decursinol
      angelate from human liver microsomes incubations using HPLC-UV and LC-MS/MS
      methods and assessed the in vivo metabolites in mouse plasma from a one-dose PK
      study. Decursin and decursinol angelate have different metabolite profiles. Nine
      metabolites of decursin and nine metabolites of decursinol angelate were
      identified in human liver microsome incubations besides decursinol using a hybrid
      triple quadruple linear ion trap LC-MS/MS system, and many of them were later
      verified to be also present in plasma samples from rodent PK studies. 

PMID- 24026904
TI  - Alkalistable xylanase production by alkalitolerant Paenibacillus montaniterrae
      RMV1 isolated from red mud.
AB  - The alkalitolerant and xylanolytic bacterial strain (RMV1) isolated from red mud
      pond was identified as Paenibacillus montaniterrae based on both biochemical and
      16S rDNA sequence analysis. The RMV1 bacterial isolate produced alkalistable and
      thermostable endoxylanase active over a broad range of pH (4.0-11.0) and
      temperature (20-100  degrees C), with optima at 50  degrees C and pH 9.0 with a
      T1/2 of 6.7 hours at 50  degrees C. This is the first report on the isolation of
      P. montaniterrae from bauxite residue with quite a high xylanase producing
      ability.

PMID- 24026905
TI  - Crack-free periodic porous thin films assisted by plasma irradiation at low
      temperature and their enhanced gas-sensing performance.
AB  - Homogenous thin films are preferable for high-performance gas sensors because of
      their remarkable reproducibility and long-term stability. In this work, a low
      temperature fabrication route is presented to prepare crack-free and homogenous
      metal oxide periodic porous thin films by oxygen plasma irradiation instead of
      high temperature annealing by using a sacrificial colloidal template. Rutile SnO2
      is taken as an example to demonstrate the validity of this route. The crack-free
      and homogenous porous thin films are successfully synthesized on the substrates
      in situ with electrodes. The SnO2 porous thin film obtained by plasma irradiation
      is rich in surface OH groups and hence superhydrophilic. It exhibits a more
      homogenous structure and lower resistance than porous films generated by
      annealing. More importantly, such thin films display higher sensitivity, a lower
      detection threshold (100 ppb to acetone) and better durability than those that
      have been directly annealed, resulting in enhanced gas-sensing performance. The
      presented method could be applied to synthesize other metal oxide homogenous thin
      films and to fabricate gas-sensing devices with high performances.

PMID- 24026906
TI  - In situ fiber-optical monitoring of cytosolic calcium in tissue explant cultures.
AB  - We present a fluorescence-lifetime based method for monitoring cell and tissue
      activity in situ, during cell culturing and in the presence of a strong
      autofluorescence background. The miniature fiber-optic probes are easily
      incorporated in the tight space of a cell culture chamber or in an endoscope. As
      a first application we monitored the cytosolic calcium levels in porcine tracheal
      explant cultures using the Calcium Green-5N (CG5N) indicator. Despite the
      simplicity of the optical setup we are able to detect changes of calcium
      concentration as small as 2.5 nM, with a monitoring time resolution of less than
      1 s.

PMID- 24026909
TI  - Isolation of cross-reactive human monoclonal antibodies that prevent binding of
      human noroviruses to histo-blood group antigens.
AB  - In order to identify the repertoire of antibodies generated on natural infection
      of norovirus (NoV) in humans, and to characterize the human monoclonal antibodies
      against NoV, three phage-displayed antibody libraries originating from healthy
      person(s) were screened using purified virus-like particles (VLPs) of strain
      Narita 104 (r104, genogroup II, genotype 4) or strain Chiba 407 (rCV, genogroup
      I, genotype 4) as antigens. On screening with r104, 62 clones were isolated.
      Among these antibodies, two clones, 12A11 and 12B10, showed intra-genogroup cross
      reactivity to genotypes 1, 3-7, 12, and 14, and genotypes 1, 4, 6, and 7 of
      genogroup II, respectively. In addition, antibodies belonging to the same group
      were isolated from two different libraries. On screening with rCV, five clones
      were isolated, two of which were cross-reactive. One, CV-2F5, reacted to
      genotypes 1-4, and 8 of genogroup I, and the other, CV-1A5, showed inter
      genogroup cross-reactivity to all the VLPs employed in this study. The blocking
      activities of the monoclonal antibodies against the interaction of homotypic VLPs
      (VLPs used in the panning procedure) with histo-blood group antigens were also
      assessed as an alternative to neutralization assay. Although the blocking
      activity of 12A11 was partially limited 12B10 prevented the binding of r104 to
      histo-blood group antigens that had been reported to bind r104. The blocking
      activity of CV-2F5 against the attachment of rCV to suitable histo-blood group
      antigens was weak, but the blocking activity of CV-1A5 was well recognized. Thus,
      12B10 and CV-1A5 were suggested to be cross-reactive monoclonal antibodies with
      neutralizing activity.

PMID- 24026910
TI  - Problems and solutions in laboratory testing for hemophilia.
AB  - A diagnosis of hemophilia A or hemophilia B begins with clinical assessment of
      the patient and is facilitated by laboratory testing. The influence of the latter
      on a diagnosis of hemophilia A or hemophilia B is clear-a diagnosis cannot be
      made without laboratory confirmation of a deficiency of factor FVIII (FVIII) or
      factor IX (FIX), respectively. Moreover, the degree of hemophilia severity is
      specifically characterized by laboratory test results. In turn, patient
      management, including choice and application of therapies, is influenced by the
      diagnosis, as well as by identification of respective disease severity. An
      incorrect diagnosis may lead to inappropriate management and unnecessary therapy,
      and thus to adverse outcomes. Moreover, identification of factor inhibitors in
      hemophilia will lead to additional and differential treatments, and incorrect
      identification of inhibitors or inhibitor levels may also lead to inappropriate
      management. Problems in hemophilia diagnosis or inhibitor detection can occur at
      any stage in the clinical diagnosis/laboratory interface, from the "pre
      preanalytical" to "preanalytical" to "analytical" to "postanalytical" to "post
      postanalytical." This report outlines the various problems in laboratory testing
      for hemophilia and provides various strategies or solutions to overcome these
      challenges. Although some outlined solutions are specific to the potential errors
      related to hemophilia, others are general in nature and can be applied to other
      areas of laboratory hemostasis. Key to improvement in this area is adoption of
      best practice by all involved, including clinicians, phlebotomists, and
      laboratories. Also key is the recognition that such errors may occur, and thus
      that clinicians should assess laboratory test results in the context of their
      patient's clinical history and follow-up any potential errors, thus avoid
      misdiagnoses, by requesting repeat testing on a fresh sample. 

PMID- 24026911
TI  - Defining severity of hemophilia: more than factor levels.
AB  - Patients with severe hemophilia generally exhibit a severe bleeding phenotype
      with bleeding into joints or muscles at an early age. Although the severity and
      frequency of bleeding symptoms correlate with the residual factor VIII/IX
      (FVIII/IX) activity in the plasma, a considerable variability in bleeding
      pattern, FVIII/IX concentrate utilization, and joint damage has been observed. A
      subset of 10 to 15% of patients with severe hemophilia A shows a milder disease
      phenotype with significantly reduced frequencies of spontaneous bleeding and
      lower requirements for factor concentrate. This mitigated clinical phenotype is
      determined by the underlying mutations in the F8/F9 genes, genetic alterations
      and polymorphisms in other genes of the hemostasis system, differences in
      inflammatory and immune response genes, limitations in laboratory diagnostics, as
      well as environmental factors. Identification of disease-modifying factors in
      hemophilia may influence treatment decisions, such as starting and tailoring
      prophylaxis according to the specific clinical phenotype, rather than just the
      laboratory-defined degree of severity. This review focuses on the current
      information of factors mitigating the clinical presentation of hemophilia and
      contributing to its high phenotypic heterogeneity. 

PMID- 24026912
TI  - Fabrication of poly(lactic-co-glycolic acid) scaffolds containing silk fibroin
      scaffolds for tissue engineering applications.
AB  - The present study deals with the fabrication of poly(lactic-co-glycolic acid)
      (PLGA) scaffolds modified with silk fibroin for biomedical application. The PLGA
      solutions were added with salt particles and pressed with high pressures; which
      were further subjected to salt leaching resulting in the creation of large sized
      pores in the PLGA scaffolds. To fill up these pores, 2%, 4%, and 8% of silk
      solutions were added, however, the addition created extra small sized pores. The
      scaffolds were characterized by various state of techniques; the scanning
      electronic microscopy revealed the large sized pores in the pristine scaffold can
      be tailored into smaller architecture by the addition of silk fibroin. The
      contact angle measurements confirmed the introduction of silk helped to change
      the hydrophobic nature of PLGA into hydrophilic, which is the main constrain for
      PLGA. The mechanical properties of scaffold can be easily improved by applying
      the higher amounts of silk into the scaffolds. The thermal gravimetric analyses
      and fourier transform infrared spectroscopy confirmed the presence of silk
      fibroin in scaffolds. The cell viability and cell attachment was checked by
      culturing the scaffolds with NIH 3T3 fibroblasts and chondrocytes. Furthermore,
      these results revealed that the introduction of silk had significant impact on
      the viability of fibroblast also had a good affinity for cell attachment and
      infiltration of human chondrocytes in scaffolds after culturing the cells for 2
      and 5 weeks of time.

PMID- 24026913
TI  - Brief Report: Atypical expression of distress during the separation phase of the
      strange situation procedure in infant siblings at high risk for ASD.
AB  - Previous studies have provided preliminary evidence that disruptions in cry
      acoustics may be part of an atypical vocal signature of autism early in life. We
      examined the acoustic characteristics of cries extracted from the separation
      phase of the strange situation procedure in a sample of toddler of younger
      siblings of a child with autism spectrum disorder-autism spectrum disorders (ASD)
      (high risk, HR) and a low risk (LR) group. Cry samples derived from vocal
      recordings of 15-month-old HR (n = 13) and LR infants (n = 14) were subjected to
      acoustic analyses. HR toddlers, compared to those with LR, produced cries that
      were shorter and had a higher fundamental frequency (F0). Three HR toddlers later
      classified with an ASD at 36 months (autistic disorder in all cases) produced
      cries that had among the highest F0 and shortest durations. Taken together these
      results indicate that toddlers at high risk for ASD (and those with an ASD)
      express atypical patterns of distress in response a social stressor. Implications
      for early diagnosis and parenting are discussed. 

PMID- 24026914
TI  - A 5-year hospital prevalence of child and adolescent psychiatric disorders from
      central India.
AB  - OBJECTIVE: To examine the 5-year hospital prevalence of child and adolescent
      mental disorders from Central India. METHODS: Using systemic random sampling
      method, of the 4410 families screened, 4278 children (607 aged 0 to 3 y and 3671
      between 4 to 16 y) attending outpatient services of department of pediatrics at
      the tertiary rural hospital from June 2006 through December 2010 were evaluated.
      Standardized appropriate psychometric tools were used for both groups. Diagnostic
      interviews were administered and DSM-IV diagnoses were determined by consensus
      between two psychiatrists. A comprehensive hospital registration system provided
      the denominator. RESULTS: Of the 4410 families screened, 4278 (97 %) of the
      subjects completed interviews. The overall prevalence of psychiatric disorders
      was found to be 20.8 %. Most common psychiatric disorders in group A were mental
      retardation (5.6 %) followed by epilepsy (2 %) whereas in group B, depressive
      disorder (3.73 %) were followed by non-organic enuresis (2.18 %) and ADHD (1.7
      %). Eighty one percent of the parents from group A and 83 % of parents from group
      B of the children affected with psychiatric disorders and neurobehavioral
      problems had reported that they have had never thought of taking psychiatric
      consultation for their children. CONCLUSIONS: The results of the study have
      helped in bridging and supporting the propositions in child epidemiology in India
      and also have implications for clinical training and practice.

PMID- 24026915
TI  - Acute myeloid leukemia presenting as mediastinal mass.

PMID- 24026916
TI  - Tips for telephone and electronic medical consultation.
AB  - The world is gradually shrinking in terms of time, and communications, while
      expanding in terms of population and distances. Patients demand and expect
      telephone and e-mail consultations and medical professionals are only too happy
      to oblige. However, a telephone consult is never so satisfying for the patients
      and well as the doctor as a face consult. Besides much essential information,
      cues and clues to diagnosis may be missed only with an audio input from patients.
      A telephone consult should be offered only to know the patient, and only after a
      prior face consult. It should be ensured that the patient can definitely
      understand, and follow the directions, and manage the disorder at home. While a
      telephone consultation may be considered convenient and short, there may be
      several disadvantages of such consultation, a wrong diagnosis and an
      inappropriate prescription being just two of them. Telephone etiquette should be
      followed by the staff and the physician. A triage system may be set up to filter
      calls that need to be necessarily answered by the physician himself. Telephone
      consults should be charged, and should be followed by a face consult as soon as
      possible. E-mail consultations are governed essentially by the same principles
      that govern telephone consultations. There is a slight advantage of e-mail
      consultation in that reports can be submitted online, including radiological
      reports. However, confidentiality is an important and uncertain issue in cyber
      space. A memorandum of understanding maybe signed between the patient and the
      physician. The information provided on e-mail should be of a general nature and a
      face consult should precede e-mail consultation. Patients may be referred to web
      resources for information. Telemedicine is a useful tool to obtain a medical
      diagnosis and to provide medical advice, and is likely to be used vastly in the
      near future. 

PMID- 24026917
TI  - Type 2 diabetes mellitus in children and adolescents.
AB  - Type 2 diabetes mellitus (T2DM) is a chronic progressive disease with high
      morbidity and mortality rates. Previously an adult onset disease, it is now being
      diagnosed more and more in childhood and adolescence. Lately, Asia has become the
      epicenter of this epidemic. Childhood T2DM is a new challenge for the
      pediatrician. Due to similarities in presentation, children may initially be
      misdiagnosed with Type 1 diabetes mellitus (T1DM). Most oral anti-diabetic agents
      have not been approved for use in adolescents, and there is a concern for safety
      of their use. Lifestyle intervention is difficult to conduct, and adherence to
      recommendations is lower in adolescents than in adults with T2DM. Higher
      incidence and early onset of co-morbidities, with lack of long term outcomes data
      make the management problematic. In many communities, due to a shortage of
      specialists, general practitioners will treat children with T2DM. Guidelines
      cited in this review are designed to help with the diagnostic process and
      management. 

PMID- 24026918
TI  - Biodegradation of epoxyconazole and piraclostrobin fungicides by Klebsiella sp.
      from soil.
AB  - Three bacterial strains have been isolated from soil in which soybean had been
      continuously cropped and treated with Opera((r)), a fungicide containing
      epoxyconazole and pyraclostrobin. The three strains (1,805, 2,801 and 3,803),
      obtained from soil at 80-100 cm depth, were selected on medium containing 0.03%
      Opera((r)). Morphological examination revealed that the strains were Gram
      negative, and two of them (1,805 and 2,801) exhibited polymorphism. The growth
      profiles demonstrated that 1,805 and 3,803 were more efficient growing in the
      presence of Opera((r)) than 2,801. Maximum growth was reached between 24 and 48
      h, however, 2,801 was not able to survive after this period. The total protein
      content produced by 1,805, 2,801 and 3,803 in liquid selective medium containing
      Opera((r)) were 111.0 +/- 0.02, 80.0 +/- 0.05 and 130.5 +/- 0.07 MUg/ml,
      respectively. According to its biochemical and molecular features, strain 1,805
      was identified as Klebsiella sp. On the basis of the characteristics presented
      (facultative anaerobic nature, polymorphic character and capacity of growing in
      the presence of Opera((r))) strain 1,805 seems to be able to degrade the
      epoxyconazole and pyraclostrobin. 

PMID- 24026919
TI  - Growth inhibition and excessive branching in Aphanomyces cochlioides induced by
      2,4-diacetylphloroglucinol is linked to disruption of filamentous actin
      cytoskeleton in the hyphae.
AB  - We observed that 2,4-diacetylphloroglucinol (DAPG), a major antimicrobial
      metabolite produced by a rhizoplane bacterium Pseudomonas fluorescens ECO-001
      inhibited mycelial growth of a damping-off phytopathogen Aphanomyces cochlioides
      AC-5 through inducing excessive branching and curling in the hyphae. This study
      aimed to unravel the mode of action of DAPG caused excessive branching, curling
      and growth inhibition of AC-5 hyphae by detecting localized changes in the
      cortical filamentous actin (F-actin) organization by rhodamine-conjugated
      phalloidin. Confocal laser scanning microscopic observations revealed that both
      living bacteria and DAPG severely disrupted the organization of F-actin in the A.
      cochlioides hyphae in a similar manner. Furthermore, an inhibitor of F-actin
      polymerization, latrunculin B also induced similar growth inhibition, excessive
      branching and caused disruption of F-actin in the AC-5 hyphae. Our results
      suggested that growth inhibition and excessive branching induced in A.
      cochlioides by DAPG is likely to be linked to the disruption of F-actin
      cytoskeleton in the affected hyphae. This is the first report on disruption of
      cytoskeleton of a eukaryotic A. cochlioides by a well-known biocontrol metabolite
      DAPG secreted from a prokaryotic bacterium ECO-001. 

PMID- 24026920
TI  - Production of diosgenin from yellow ginger (Dioscorea zingiberensis C. H. Wright)
      saponins by commercial cellulase.
AB  - A commercial cellulase was first assessed to be effective in hydrolyzing glycosyl
      at the C-3 and C-26 positions in steroidal saponins from yellow ginger (Dioscorea
      zingiberensis C. H. Wright) to diosgenin, a very important chemical in the
      pharmaceutical industry. The effect of different parameters on enzyme hydrolysis
      was further investigated by systematically varying them. The highest yield was
      achieved when the hydrolysis ran at 55 degrees C and pH 5.0 with an enzyme to
      substrate ratio of 15 * 10(3) U/g. The biotransformed products identified using
      TLC and HPLC confirmed that the cellulase was capable of releasing diosgenin from
      steroidal saponins. Moreover, the biotransformation process was explored by LC-MS
      and LC-MS/MS analysis. Enzymatic hydrolysis together with 40 % of the original
      sulphuric acid used increased the diosgenin yield by 15.4 +/- 2.7% than
      traditional method. Therefore, the commercial cellulase may serve as a promising
      tool for industrial diosgenin production and for further use in saponin
      modification. 

PMID- 24026921
TI  - Improvement of alcoholic fermentation by calcium ions under enological conditions
      involves the increment of plasma membrane H(+)-ATPase activity.
AB  - The effect of Ca(2+) on alcoholic fermentation and plasma membrane H(+)-ATPase
      activity of wine yeast under enological conditions were investigated in this
      study. The results showed that fermentation rate, cell growth and ethanol
      production were improved by 0.5 and 1.5 mM Ca(2+) supplementation, which
      correlated well with the increment of ATPase activity and protein levels.
      Considering the important role of ATPase in the tolerance of yeast to ethanol,
      the improvement could be, at least partially, attributed to the increment of
      ATPase activity. No activation of ATPase by Ca(2+) was observed in the early
      phase of fermentation and the increment of activity was only observed when
      ethanol concentration exceeded 6.5%. Therefore, the enhancement of ATPase
      activity by Ca(2+) was ascribed to alleviating the inhibition of ATPase activity
      by ethanol through protection of membrane structure. Our results suggest that,
      besides maintenance of cell membrane structure, the increment of plasma membrane
      ATPase activity was also responsible for the improvement of alcoholic
      fermentation by Ca(2+) supplementation. 

PMID- 24026922
TI  - Isolation, evaluation and characterization of Bacillus subtilis from cotton
      rhizospheric soil with biocontrol activity against Fusarium oxysporum.
AB  - Present investigation is based on the isolation of Bacillus subtilis from cotton
      rhizosphere and their evaluation as biocontrol agent against Fusarium oxysporum.
      The production of extracellular hydrolytic enzyme was studied for determining the
      antagonism. 43% of 21 isolates were identified under the B. subtilis group on the
      basis of biochemical characterization. 38% isolates showed competitive activity
      against Fusarium oxysporum and exhibit more than 50% mycelial inhibition in dual
      culture bioassay. The pot assay of cotton by seed treatment and soil amendment
      technique under green house condition showed the competent activity of the
      isolates in preventing the wilting of cotton seedlings due to F. oxysporum
      infection. SVI values of 30 day old seedlings indicated that the soil inoculation
      with B. subtilis BP-2 and seed treatment with B. subtilis BP-9 significantly
      promoted the growth of cotton seedlings. RAPD profiling revealed the diversity in
      the Bacillus subtilis group, ranging from 10 to 32%. The discriminative pattern
      among the isolates belonging to the same species was validated by 16S rDNA
      partial sequencing which identified them into four different strains of B.
      subtilis. 

PMID- 24026923
TI  - Utilization of dibenzothiophene as sulfur source by Microbacterium sp. NISOC-06.
AB  - Oil-polluted soils were sampled from National Iranian South Oil Company (NISOC)
      for isolation and screening of C-S and not C-C targeted Dibenzothiophene (DBT)
      degrading microorganisms. Microbacterium sp. NISOC-06, a C-S targeted DBT
      degrading bacterium, was selected and its desulfurization ability was studied in
      aqueous phase and water-gasoline biphasic systems. The 16srRNA gene was amplified
      using universal eubacteria-specific primers, PCR product was sequenced and the
      sequence of nearly 1,500 bp 16srDNA was studied. Based on Gas Chromatography
      results Microbacterium sp. NISOC-06 utilized 94.8% of 1 mM DBT during the 2 weeks
      of incubation. UV Spectrophotometry and biomass production measurements showed
      that the Microbacterium sp. NISOC-06 was not able to utilize DBT as a carbon
      source. There was no accumulation of phenolic compounds as Gibb's assay showed.
      Biomass production in a biphasic system for which DBT-enriched gasoline was used
      as the sulfur source indicated the capability of Microbacterium sp. NISOC-06 to
      desulfurize gasoline. 

PMID- 24026924
TI  - Biotransformation of eugenol by suspension cultures of transgenic crown galls of
      Panax quinquefolium and suspension cultures of Nicotiana tabacum.
AB  - The biocatalytic ability of transgenic crown galls of Panax quinquefolium was
      evaluated by using eugenol (1) as a substrate and suspension cultures of
      Nicotiana tabacum as control system. Three biotransformed products, namely: 2
      methoxy-4-(2-propenyl)phenyl-O-beta-D-glucopyranoside (2, 67.11%), 2-methoxy-4-(2
      propenyl)phenyl-O-beta-D-glucopyranosyl (6' -> 1")-beta-D-xylopyranoside (3,
      2.85%) and methyl eugenol (4, 14.30%) were obtained after 5 days of
      administration of eugenol to the suspension cultures of transgenic crown galls of
      P. quinquefolium. In contrast, only one product, compound 2 (15.41%), was
      obtained in suspension cultures of N. tabacum after 5 days of incubation. The
      results indicated that the glycosylation ability of transgenic crown galls of P.
      quinquefolium was much higher than that of the cultured cells of N. tabacum. 

PMID- 24026925
TI  - Characteristics and antimicrobial activity of Bacillus subtilis strains isolated
      from soil.
AB  - Antagonistic Bacillus strains were isolated from soil and analyzed for the
      purpose of determining whether they could be used as natural biological agents.
      Primary in vitro screening for antagonism of the isolates was performed against
      five phytopathogenic mould fungi. Strains TS 01 and ZR 02 exhibited the most
      pronounced inhibitory effects. They were identified as Bacillus subtilis on the
      basis of their morphological, cultural and physiology-biochemical properties as
      well as their hierarchical cluster analysis conducted by means of computer
      program SPSS. The antimicrobial activity of the strains from cultural medium and
      sterile filtrate were determined in vitro against a great number of predominantly
      phytopathogenic fungi and bacteria. TS 01 and ZR 02 strains exhibited very broad
      and at the same time degree varying antibiotic spectra of activities against both
      Gram-positive and Gram-negative microorganisms. Many of them were tested against
      sensitivity to the antimicrobial action of B. subtilis for the very first time.
      B. subtilis TS 01 and ZR 02 showed highest antifungal activity (sterile zone in
      diameter over 37 mm) against Alternaria solani, Botrytis cinerea, Monilia
      linhartiana 869, Phytophthora cryptogea 759/1 and Rhizoctonia sp. The most
      sensitive bacterial species were found to be Pseudomonas syringae pv. tomato Ro
      and Xanthomonas campestris with sterile zones 48.0 and 50.0 mm in diameter,
      respectively. The latter draws a conclusion that the isolated and identified
      Bacillus subtilis strains are promising natural biocontrol agents and should be
      further studied and tested for control of numerous plant diseases. 

PMID- 24026926
TI  - Comparison of citric acid production from glycerol and glucose by different
      strains of Yarrowia lipolytica.
AB  - A wild type strain A-101 of Y. lipolytica and its three acetate-negative mutants
      (Wratislavia 1.31, Wratislavia AWG7, and Wratislavia K1) were compared for the
      production of citric acid from glucose and glycerol (pure and crude) in batch
      cultures. The substrates were used either as single carbon sources or as mixtures
      of glucose and pure or crude glycerol. The kinetic parameters, i.e., the
      volumetric citric acid production rate and yield obtained in the study show that
      the Wratislavia 1.31 and Wratislavia AWG7 strains produced the highest amount of
      citric acid from glycerol, with a yield from 0.40 to 0.53 g g(-1). This substrate
      was found to be a better carbon source for the biosynthesis of citric acid than
      glucose. The results obtained with the same strains have shown low content of
      isocitric acid and polyols, such as erythritol and mannitol. Y. lipolytica A-101
      strain produced the highest amount of isocitric acid, from 13.8 to 21% isocitric
      acid in the sum of citric acids. However, the highest concentrations of
      erythritol were found in cultures with Y. lipolytica Wratislavia K1, from 18.1 to
      30 g l(-1), for glucose and pure glycerol, respectively. 

PMID- 24026927
TI  - Effect of pH on growth and biochemical responses of Dunaliella bardawil and
      Chlorella ellipsoidea.
AB  - The goal of the present investigation was to study the effect of pH on growth and
      biochemical responses of Dunaliella bardawil and Chlorella ellipsoidea when
      exposed to different pH values. The two tested microalgae could grow in a wide
      range of pH (4-9 for D. bardawil and 4-10 for C. ellipsoidea). The dry weight
      gain and the biochemical components of D. bardawil were greatly enhanced at pH
      7.5. In contrast, dry weight and carbohydrate content of C. ellipsoidea attained
      their maximum values at the alkaline pH. On the other hand, the protein content
      of C. ellipsoidea recorded its highest value at pH 4, while the pigment content
      of the same alga was highest at pH 4, 6, and 7.5 and decreased at alkaline pH.
      Both pH 6 and pH 9 stimulated the accumulation of beta-carotene, vitamin E and
      vitamin C in D. bardawil, with the highest values of the three compounds recorded
      at pH 9. In the case of C. ellipsoidea, beta-carotene content increased at pH 6
      and pH 10 as compared with the control, but the amount of beta-carotene was much
      higher at pH 6 than at pH 10. Vitamin E content was higher in C. ellipsoidea
      cells at pH 10 than at pH 6. Both pH 6 and pH 10 caused a significant decline in
      vitamin C content of C. ellipsoidea. 

PMID- 24026928
TI  - Isolation and characterization of plant growth promoting bacteria from non
      rhizospheric soil and their effect on cowpea (Vigna unguiculata (L.) Walp.)
      seedling growth.
AB  - The efficacy of four potential phosphate solubilizing Enterobacter isolated from
      non-rhizospheric soil in Western ghat forest in India. Plant growth promoting
      ability of these isolates was evaluated in cowpea. All are gram negative, rod
      shaped, 0.8-1.6 mm in size, and psychrotrophic in nature, grow from 5 to 40
      degrees C (optimum temp. 28 +/- 2 degrees C). All isolates exhibits growth at a
      wide range of pH 6-12, optimum at pH 7.0 and tolerates up to 7% (w/v) salt
      concentration. 16S rRNA gene sequencing reveals the confirmation of isolates to
      Enterobacter aerogenes sp. (NII-0907 and NII-0929), Enterobacter cloacae subsp.
      cloacae sp. (NII-0931) and Enterobacter asburiae sp. (NII-0934) with which they
      share >99% sequence similarity. Under in vitro conditions, all the four isolates
      were found to produce indole acetic acid, P-solubilization and hydrogen cyanide.
      The P-solubilizing activity coincided with a concomitant decrease in pH of the
      medium (pH 7.0-<3.0). The plant growth promotion properties were demonstrated
      through a cow pea (Vigna unguiculata (L.) walp) based bioassay under greenhouse
      conditions. Although the bacterial inoculation was found to result in significant
      increment in root, shoot and biomass and it stimulated bacterial counts in the
      rhizosphere. Hence, these isolates can further formulated and used for field
      application. 

PMID- 24026929
TI  - Microbial communities and chemical changes during fermentation of sugary
      Brazilian kefir.
AB  - The microorganisms associated with sugary Brazilian kefir beverage were
      investigated using a combination of culture-dependent and -independent methods. A
      total of 289 bacteria and 129 yeasts were identified via phenotypic and genotypic
      methods. Lb. paracasei (23.8%) was the major bacterial isolate identified,
      followed by Acetobacter lovaniensis (16.31%), Lactobacillus parabuchneri
      (11.71%), Lactobacillus kefir (10.03%) and Lactococcus lactis (10.03%).
      Saccharomyces cerevisiae (54.26%) and Kluyveromyces lactis (20.15%) were the most
      common yeast species isolated. Scanning electron microscopy showed that the
      microbiota was dominated by lemon-shaped yeast cells growing in close association
      with Lactobacillus (long and curved). Some lactic acid bacteria detected by
      sequence analysis of DGGE (denaturing gradient gel electrophoresis) bands were
      not recovered at any time through fermentation by plating. Conversely, DGGE
      fingerprints did not reveal bands corresponding to some of the species isolated
      by culturing methods. The bacteria Acetobacter lovaniensis and the yeast
      Kazachstania aerobia are described for the first time in sugary kefir. During the
      24 h of fermentation, the concentration of lactic acid ranged from 0.2 to 1.80
      mg/ml, and that of acetic acid increased from 0.08 to 1.12 mg/ml. The production
      of ethanol was limited, reaching a final mean value of 1.24 mg/ml. 

PMID- 24026930
TI  - Cloning of triose phosphate isomerase gene from an antarctic psychrophilic
      Pseudomonas sp. by degenerate and splinkerette PCR.
AB  - Psychrophiles are organisms that thrive in cold environments. One of the
      strategies for their cold adaptation is the ability to synthesize cold-adapted
      enzymes. These enzymes usually display higher catalytic efficiency and
      thermolability at lower temperatures compared to their mesophilic and
      thermophilic counterparts. In this work, a psychrophilic bacterial isolate
      codenamed pi9 was selected for the cloning of the gene encoding triose phosphate
      isomerase (TIM), an enzyme in the glycolytic pathway. Based on 16S rRNA gene
      sequence analysis, this isolate was identified as a species of the genus
      Pseudomonas under the P. fluorescens group. The cloning of a 816 bp fragment of
      TIM gene which covers the 756 bp open reading frame was achieved by a combination
      of degenerate and splinkerette PCRs. The partial sequence of this gene was first
      PCR amplified by using degenerate primers and the flanking sequences were
      subsequently amplified by splinkerette PCR technique. Amino acid sequence of the
      cloned TIM was 97% identical to TIM from Pseudomonas fluorescens and shared 51%
      identity with the TIM from psychrophilic Vibrio sp. This work demonstrated the
      use of multiple PCR techniques to clone a gene without prior knowledge of its
      sequence. The cloning of the TIM gene by PCR was more rapid and cost effective
      compared to the traditional genomic library construction and screening method.
      Homology model of the TIM protein in this study was generated based on
      Escherichia coli TIM crystal structure. The model could serve as a hypothetical
      TIM structure from a psychrophilic microorganism for further investigation into
      areas that showed deviations from the known mesophilic TIM structures. 

PMID- 24026931
TI  - Effect of ethanol and hydrogen peroxide on poly(3-hydroxybutyrate) biosynthetic
      pathway in Cupriavidus necator H16.
AB  - Exposition of Cupriavidus necator to ethanol or hydrogen peroxide at the
      beginning of the stationary phase increases poly(3-hydroxybutyrate) (PHB) yields
      about 30%. Hydrogen peroxide enhances activity of pentose phosphate pathway that
      probably consequently increases intracellular ratio NADPH/NADP(+). This effect
      leads to stimulation of the flux of acetyl-CoA into PHB biosynthetic pathway and
      to an increase of enzymatic activities of beta-ketothiolase and acetoacetyl-CoA
      reductase while activity of PHB synthase remains uninfluenced. During ethanol
      metabolisation, in which alcohol dehydrogenase is involved, acetyl-CoA and
      reduced coenzymes NAD(P)H are formed. These metabolites could again slightly
      inhibit TCA cycle while flux of acetyl-CoA into PHB biosynthetic pathway is
      likely to be supported. As a consequence of TCA cycle inhibition also less free
      CoA is formed. Similarly with hydrogen peroxide, activities of beta-ketothiolase
      and acetoacetyl-CoA reductase are increased which results in over-production of
      PHB. Molecular weight of PHB produced under stress conditions was significantly
      higher as compared to control cultivation. Particular molecular weight values
      were dependent on stress factor concentrations. This could indicate some
      interconnection among activities of beta-ketothiolase, acetoacetyl-CoA reductase
      and PHB molecular weight control in vivo. 

PMID- 24026932
TI  - Molecular cloning and homology modelling of a subtilisin-like serine protease
      from the marine fungus, Engyodontium album BTMFS10.
AB  - An alkaline protease gene (Eap) was isolated for the first time from a marine
      fungus, Engyodontium album. Eap consists of an open reading frame of 1,161 bp
      encoding a prepropeptide consisting of 387 amino acids with a calculated
      molecular mass of 40.923 kDa. Homology comparison of the deduced amino acid
      sequence of Eap with other known proteins indicated that Eap encode an
      extracellular protease that belongs to the subtilase family of serine protease
      (Family S8). A comparative homology model of the Engyodontium album protease
      (EAP) was developed using the crystal structure of proteinase K. The model
      revealed that EAP has broad substrate specificity similar to Proteinase K with
      preference for bulky hydrophobic residues at P1 and P4. Also, EAP is suggested to
      have two disulfide bonds and more than two Ca(2+) binding sites in its 3D
      structure; both of which are assumed to contribute to the thermostable nature of
      the protein. 

PMID- 24026933
TI  - Genetic diversity of elite rhizobial strains of subtropical and tropical legumes
      based on the 16S rRNA and glnII genes.
AB  - Biodiversity of diazotrophic symbiotic bacteria in the tropics is a valuable but
      still poorly studied resource. The objective of this study was to determine if a
      second housekeeping gene, glnII, in addition to the 16S rRNA, can be employed to
      improve the knowledge about taxonomy and phylogeny of rhizobia. Twenty-three
      elite rhizobial strains, very effective in fixing nitrogen with twenty-one herbal
      and woody legumes (including species from fourteen tribes in the three
      subfamilies of the family Leguminosae) were selected for this study; all strains
      are used as commercial inoculants in Brazil. Complete sequences of the 16S rRNA
      and partial sequences (480 bp) of the glnII gene were obtained. The same primers
      and amplification conditions were successful for sequencing the glnII genes of
      bacteria belonging to five different rhizobial genera-Bradyrhizobium,
      Mesorhizobium, Methylobacterium, Rhizobium, Sinorhizobium)-positioned in
      distantly related branches. The analysis of the concatenated genes (16S rRNA +
      glnII) considerably improved information about phylogeny and taxonomy of rhizobia
      in comparison to the single analysis of the 16S rRNA. Nine strains might belong
      to new species. The complementary analysis of the glnII gene was successful with
      all strains and improved the phylogenetic clustering and clarified the taxonomic
      position of several strains. The strategy of including the analysis of glnII, in
      addition to the 16S rRNA, is cost- and time- effective for the characterization
      of large rhizobial culture collections or in surveys of many isolates. 

PMID- 24026934
TI  - Enhanced production of squalene in the thraustochytrid Aurantiochytrium mangrovei
      by medium optimization and treatment with terbinafine.
AB  - Squalene is an effective chemopreventive agent in reducing the incident of
      coronary heart disease and cancer. It is also a strong antioxidant used
      extensively in the food and cosmetic industries. Microbial sources of squalene
      are being explored in recent years. The objective of this study is to increase
      the squalene content and yield in the thraustochytrid, Aurantiochytrium mangrovei
      FB3 through medium optimization and the treatment with terbinafine, an inhibitor
      of squalene monooxygenase in the sterol biosynthetic pathway. The highest biomass
      concentration of 21.2 g l(-1) was obtained at a glucose concentration of 60 g l(
      1), while the highest specific growth rate of 0.077 h(-1) and the growth yield
      coefficient of 0.44 g g(-1) based on glucose were achieved at a lower glucose
      concentration (30 g l(-1)). The addition of terbinafine led to a slight
      inhibition of cell growth whereas an obvious increase in squalene content was
      observed at terbinafine concentrations of 10 and 100 mg l(-1), which corresponded
      to an increase of 36 and 40% in squalene content, respectively compared to the
      control. The addition of terbinafine was thus effective in inducing the
      accumulation of squalene in A. mangrovei. This study not only demonstrated the
      production potential of squalene by A. mangrovei, but also provided novel
      information on the accumulation effect of terbinafine on the biosynthesis of an
      essential intermediate involved in sterol metabolic pathway. 

PMID- 24026935
TI  - Estimation of bioavailability and potential risks of naphthalene in soils with
      solid phase microextraction.
AB  - A series of batch experiments were conducted to observe the variations of
      bioavailability of naphthalene in different types of soil with indigenous
      microorganisms. Solid phase microextraction (SPME) was employed to estimate the
      bioavailability of naphthalene in the soils. Various soil properties were
      attained by artificially modifying soil organic matter (SOM) with the addition of
      bagasse compost and textures with the addition of original silt and clay to
      determine the correlation between the amount of biodegraded naphthalene after 300
      h and the amount of extractable naphthalene by SPME. Experimental results
      indicated that the biodegradation rate increased from 0.30 (sandy loam) to 0.48
      (silty loam) MUg g(-1) h(-1) when soils had more silt/clay. In contrast, the
      biodegradation rate slightly decreased from 0.30 (1.3% SOM) to 0.20 (5.2% SOM)
      MUg g(-1) h(-1) when the SOM was high. Distributions of naphthalene in soils
      after biodegradation were affected by the addition of bagasse compost. It showed
      that the bioavailability of naphthalene in soils decreased with an increase in
      SOM. Sequestration as measured by ultrasonic extractability evidently occurred
      within 4 months in aged soil samples. However, the amounts extracted by
      sonication after 4 and 16 months of aging did not statistically differ from each
      other. The SPME measurements correlated well with the amount of biodegraded
      naphthalene by indigenous microorganisms. Results of this study demonstrate that
      SPME is a promising method to estimate the bioremediation efficacy of naphthalene
      contaminated soils with various properties. 

PMID- 24026936
TI  - Enhancement of oxytetracycline production after gamma irradiation-induced
      mutagenesis of Streptomyces rimosus CN08 strain.
AB  - Streptomyces rimosus CN08 isolated from Tunisian soil produced 8.6 mg l(-1) of
      oxytetracycline (OTC) under submerged fermentation (SmF). Attempts were made for
      enhancing OTC production after irradiation-induced mutagenesis of Streptomyces
      rimosus CN08 with Co(60)-gamma rays. 125 OTC-producing colonies were obtained
      after screening on kanamycin containing medium. One mutant called Streptomyces
      rimosus gamma-45 whose OTC production increased 19-fold (165 mg l(-1)) versus
      wild-type strain was selected. gamma-45 mutant was used for OTC production under
      solid-state fermentation (SSF). Wheat bran (WB) was used as solid substrate and
      process parameters influencing OTC production were optimized. Solid-state
      fermentation increased the yield of antibiotic production (257 mg g(-1)) when
      compared with submerged fermentation. Ammonium sulphate as additional nitrogen
      source enhanced OTC level to 298 mg g(-1). Interestingly, OTC production by gamma
      45 mutant was insensitive to phosphate which opens the way to high OTC production
      even in medium containing phosphate necessary for optimal mycelia growth. 

PMID- 24026937
TI  - A method for generating precise gene deletions and insertions in Escherichia
      coli.
AB  - A simple and general method for disrupting chromosomal genes and introducing
      insertions is described. This procedure involves eliminating wild-type bacterial
      genes and introducing mutant alleles or other insertions at the original locus of
      the wild-type gene. To demonstrate the utility of this approach, the tig gene of
      Escherichia coli was replaced by homologous recombination with a cassette
      containing the chloramphenicol resistance gene and the sacB gene. The cassette
      was then removed and the tig mutant alleles were moved into the native tig
      location. Sequencing and Western blotting results demonstrated that insertions or
      deletions can be introduced precisely in E. coli using our approach. Our system
      does not require extra in vitro manipulations such as restriction digestion or
      ligation, and does not require use of specific plasmids or strains which are used
      to prevent false positive transformants caused by template plasmid
      transformation. This technique can be used widely in bacterial genome analysis. 

PMID- 24026938
TI  - Influence of stressful fermentation conditions on neutral lipids of a
      Saccharomyces cerevisiae brewing strain.
AB  - The neutral lipid fraction of the aerobically grown starter yeast culture of a
      Saccharomyces cerevisiae brewing strain, and three-first recycled yeast
      generations exposed to multiple stress factors during beer fermentation was
      studied. No pronounced changes in the cellular neutral lipid content between the
      non-stressed starter and stressed recycled cells were found. However, it was
      found that recycled yeast generations modulate their neutral lipid composition
      during fermentation. The ergosterol content was increased at the expense of
      steryl esters (SEs) and squalene, which resulted in a higher ergosterol/SEs molar
      ratio and a slightly higher ergosterol/squalene molar ratio. In addition, the
      proportion of unsaturated fatty acids, mainly palmitoleic acid increased in the
      neutral lipid fraction of the stressed recycled yeast generations. These results
      suggest that some specific neutral lipid species and fatty acids stored in the
      neutral lipid fraction are involved in the adaptive response of the brewer's
      yeast to stressful fermentation conditions. The striking finding was a high
      squalene content in the neutral lipid fraction of both the starter yeast culture
      and recycled yeast generations (22.4 vs. 19-20%, respectively), implying a
      possible biotechnological exploitation of this biologically active molecule from
      the yeast biomass. 

PMID- 24026939
TI  - One-procedure synthesis of capsiate from capsaicin by lipase-catalyzed dynamic
      transacylation.
AB  - Capsiate has a structure similar to capsaicin but no oral pungency. Furthermore,
      capsiate displayed antioxidant activity and inhibited angiogenesis and vascular
      permeability, and therefore, showed potential as a medicine and food supplement.
      Capsaicin is now commercially available, however capsiate is scarcely present in
      natural foods. We investigated the direct enzymatic conversion of a capsaicinoid
      to a capsinoid. It was observed that the rate of lipase-catalyzed acylation of
      vanillyl alcohol with nonanoic acid was faster than that of hydrolysis of N
      vanillylnonanamide to vanillyl amide and nonanoic acid in n-hexane at 70 degrees
      C. As a result, we performed a one-procedure synthesis of capsiate from capsaicin
      via lipase-catalyzed transacylation. 

PMID- 24026940
TI  - Characterization of neuronal ceroid-lipofuscinosis in 3 cats.
AB  - Three young domestic shorthair cats were presented for necropsy with similar
      histories of slowly progressive visual dysfunction and neurologic deficits.
      Macroscopic examination of each cat revealed cerebral and cerebellar atrophy,
      dilated lateral ventricles, and slight brown discoloration of the gray matter.
      Histologically, there was bilateral loss of neurons within the limbic, motor,
      somatosensory, visual, and, to a lesser extent, vestibular systems with extensive
      astrogliosis in the affected regions of all 3 cases. Many remaining neurons and
      glial cells throughout the entire central nervous system were distended by pale
      yellow to eosinophilic, autofluorescent cytoplasmic inclusions with
      ultrastructural appearances typical of neuronal ceroid-lipofuscinoses (NCLs).
      Differences in clinical presentation and neurological lesions suggest that the 3
      cats may have had different variants of NCL. Molecular genetic characterization
      in the 1 cat from which DNA was available did not reveal any plausible disease
      causing mutations of the CLN1 (PPT1), CLN3, CLN5, CLN8, and CLN10 (CTSD) genes.
      Further investigations will be required to identify the mutations responsible for
      NCLs in cats. 

PMID- 24026942
TI  - Combining environmental factors and agriculturalists' observations of
      environmental changes in the traditional terrace system of the Amalfi coast
      (southern Italy).
AB  - Terraces are traditional engineered ecosystems that affect the hydro-geological
      equilibrium, slope stability, and local communities. The aims of this paper are
      (i) identifying environmental factors that affect terrace stability in the Amalfi
      Coast, (ii) defining agriculturalists' observations on environmental changes
      within that system and (iii) exploring potentiality of these observations to
      better define conservation strategies. All available data on physical and
      ecological factors recognized to affect the terrace system were collected and
      analyzed. Interviews were conducted with agriculturalists to obtain long-term
      observations on environmental factors that interact with this system. Landslides
      are more frequent where rainfall is high and during winter. Fires have an uneven
      annual distribution, with higher frequency during summers. Agriculturalists
      detailed complex interactions among environmental factors, economic elements, and
      terraces. These observations represent a valuable resource for defining causes
      and effects of abandonment and for better addressing conservation strategies. 

PMID- 24026941
TI  - New insights and modern treatment of AL amyloidosis.
AB  - Systemic amyloidosis is a rare disease that is rarely cured. Systemic
      immunoglobulin light-chain amyloidosis (AL) is the most common type, usually the
      result of monoclonal light chains produced by a relatively indolent small plasma
      cell clone in the bone marrow. In AL, the direct toxicity of light chains, their
      misfolded intermediates, and deposition as amyloid fibrils in vital organs cause
      organ dysfunction and death. Often the diagnosis is delayed and the disease is
      advanced at presentation. Early diagnosis is possible with vigilance in clinical
      situations such as for patients with monoclonal gammopathy of undetermined
      significance who develop albuminuria or elevated cardiac biomarkers. Treatment is
      aimed at eradicating the clonal disease and restoring organ function; options
      include high dose melphalan followed by autologous stem cell transplantation,
      oral melphalan and dexamethasone, bortezomib-based combination chemotherapy and
      immunomodulatory agents such as lenalidomide or pomalidomide combined with
      dexamethasone. Cardiac involvement at baseline and the free light-chain
      hematologic response to therapy determine overall survival. Following measures of
      organ disease with cardiac and other biomarkers and of hematologic disease with
      serum free light chains is necessary to gauge organ and hematologic responses to
      therapy.

PMID- 24026943
TI  - Managing manure from China's pigs and poultry: the influence of ecological
      rationality.
AB  - We have investigated manure management practices at three farm scales in Chinese
      pig and poultry production. The concept of ecological rationality was employed to
      explore empirically how environmental concerns drive adoption of environmental
      friendly manure management technologies at different farm scales. The more
      developed Rudong County in Jiangsu Province and the less developed Zhongjiang
      County in Sichuan Province were chosen as cases for study of 258 animal breeders.
      On the contrary to our hypothesis, medium-scale farmers were not always found to
      be laggards in adoption of manure management technologies. Government ecological
      rationality played a key role to induce environmental-friendly technology
      adoption on its own, but also in cooperation with ecologically rational
      individual or network drivers. Authorities no longer applied their efforts in a
      conventional command-and-control way, but more in the form of incentives,
      stimulation, and information to farmers. Individual farmers in general showed low
      environmental responsibility in relation to manure handling. 

PMID- 24026944
TI  - Impaired sustained attention in adult patients with type 1 diabetes is related to
      diabetes per se.
AB  - BACKGROUND: Patients with type 1 diabetes have altered sleep characteristics and
      are thought to have deficits in sustained attention. We compared the sustained
      attention to response task (SART) of patients with type 1 diabetes to that of
      healthy controls, and related results with sleep characteristics and disease
      related factors. METHODS: SART was applied in 122 patients and 109 controls.
      Glucoregulation was assessed by HbA1c values and a questionnaire assessing
      glycaemic history. Clinical parameters were obtained from medical charts.
      Polyneuropathy was assessed by neurological examination and quantitative sensory
      testing. Sleep characteristics were assessed with sleep questionnaires. Anxiety
      and depression scores were assessed by the Hospital Anxiety and Depression Scale.
      RESULTS: The SART reaction time (RT) was significantly longer than in controls
      (327 +/- 5 vs. 285 +/- 3 ms, p < 0.001), although there were no significant
      differences in error scores. Repeated measurement analyses showed that diabetes
      per se was associated with prolonged RT (p < 0.001) and more commission errors (p
      = 0.010). None of the sleep-related and diabetes-related factors were
      significantly associated with these SART parameters. CONCLUSIONS: Patients with
      type 1 diabetes had impaired sustained attention, which was associated with
      diabetes per se but not with disturbed sleep characteristics.

PMID- 24026945
TI  - The evaluation of mitral valve stenosis: comparison of transthoracic
      echocardiography and cardiac magnetic resonance.
AB  - AIMS: Echocardiographic assessment of patients with mitral valve stenosis (MS)
      requires a detailed evaluation of mitral valve anatomy, mitral valve area (MVA),
      and pressure gradient and presence concomitant valve diseases. Our aim was to
      evaluate planimetric MVA and transmitral flow velocities using cardiac magnetic
      resonance (CMR) in patients with isolated MS and to compare with transthoracic
      echocardiography (TTE) to determine the reliability. METHODS AND RESULTS: Thirty
      one patients (mean age 50.4 +/- 10.2, 90.3% women) with isolated MS who were in a
      normal sinus rhythm were included in the study. Patients with ejection fraction
      <50%, atrial fibrillation, moderate-to-severe mitral valve insufficiency,
      moderate-to-severe stenosis and insufficiency of other valves, and previous
      commissurotomy and valvulotomy were excluded. Planimetric MVA and diastolic
      velocities were measured with TTE and CMR. There were strong correlations between
      measurements of planimetric MVA and transmitral diastolic velocities (P <
      0.0001). Assessment of Bland-Altman analysis revealed strong agreement on
      measuring planimetric MVA with values -0.018 cm(2) (SD = 0.98 cm(2)) and the
      limits of agreement were -0.131 to 0.094. CONCLUSION: CMR is a reliable method in
      patients with MS for diagnosis and follow-up.

PMID- 24026946
TI  - Interaction of silver nanoparticles with Escherichia coli and their cell envelope
      biomolecules.
AB  - The antibacterial effect of AgNPs was investigated by determining MIC/MBC and
      growth kinetics assay. The lowest MIC/MBC was found to be in the range of 11.25
      22.5 ug ml(-1) . The growth kinetics curve shows that 25 ug ml(-1) AgNPs strongly
      inhibits the bacterial growth. Confocal laser scanning electron microscopy (CLSM)
      shows that as the concentration of NPs increases, reduction in the number of
      cells was observed and at 50 ug ml(-1) of NPs, 100% death was noticed. Scanning
      electron microscopy (SEM) shows cells were severely damaged with pits, multiple
      depressions, and indentation on cell surface and original rod shape has swollen
      into bigger size. High resolution-transmission electron microscopic (HR-TEM)
      micrograph shows that cells were severely ruptured. The damaged cells showed
      either localized or complete separation of the cell membrane. The NPs that anchor
      onto cell surface and penetrating the cells may cause membrane damage, which
      could result in cell lysis. The interaction of AgNPs to membrane biomolecules;
      lipopolysaccharide (LPS) and L-alpha-phosphatidyl-ethanolamine (PE) were
      investigated by attenuated total reflectance-fourier transform infrared (ATR
      FTIR) spectroscopy. LPS and PE showed IR spectral changes after AgNPs exposure.
      The O-antigen part of LPS was responsible for interaction of NPs through hydrogen
      bonding. The phosphodiester bond of PE was broken by AgNPs, forming phosphate
      monoesters and resulting in the highly disordered alkyl chain. The AgNPs-induced
      structural changes in phospholipid may lead to the loss of amphiphilic
      properties, destruction of the membrane and cell leaking. The biomolecular
      changes in bacterial cell envelope revealed by ATR-FTIR provide a deeper
      understanding of cytotoxicity of AgNPs. 

PMID- 24026947
TI  - A 1,3-phenylene-bridged hexameric porphyrin wheel and efficient excitation energy
      transfer along the wheel.
AB  - A 1,3-phenylene-bridged hexameric Zn(II) porphyrin wheel was synthesized by a
      Suzuki-Miyaura coupling reaction through a one-pot or a stepwise route. The
      hexameric wheel structure was revealed by using X-ray diffraction analysis. The
      porphyrin wheel exhibits a split Soret band due to effective exciton coupling and
      displays efficient excitation energy transfer along the wheel. Measurements of
      fluorescence anisotropy decay and pump-power-dependent decay reveal a rapid
      excitation energy hopping along the wheel with a rate of 1.4 ps.

PMID- 24026948
TI  - Ultrastructure of the ciliated cells of the free-swimming larva, and sessile
      stages, of the marine sponge Haliclona indistincta (Demospongiae: Haplosclerida).
AB  - We provide a detailed, comparative study of the ciliated cells of the marine
      haplosclerid sponge Haliclona indistincta, in order to make data available for
      future phylogenetic comparisons at the ultrastructural level. Our study focuses
      on the description and analysis of the larval epithelial cells, and choanocytes
      of the metamorphosed juvenile sponge. The ultrastructure of the two cell types is
      sufficiently different to prevent our ability to conclusively determine the
      origin of the choanocytes from the larval ciliated cells. However, ciliated,
      epithelial cells were observed in a migratory position within the inner cell mass
      of the larval stages. Some cilia were observed within the cell's cytoplasm, which
      is indicative of the ciliated epithelial cell undergoing transdifferentiation
      into a choanocyte; while traces of other ciliated epithelial cells were contained
      within phagosomes, suggesting they are phagocytosed. We compared our data with
      other species described in the literature. However, any phylogenetic inference
      must wait until further detailed comparisons can be made with species whose
      phylogenetic position has been determined by other means, such as phylogenomics,
      in order to more closely link genomic, and morphological information.

PMID- 24026949
TI  - Balloon augmented Onyx embolization utilizing a dual lumen balloon catheter:
      utility in the treatment of a variety of head and neck lesions.
AB  - INTRODUCTION: Endovascular embolization for tumors and vascular malformations has
      emerged as an important preoperative adjunct prior to resection. We describe the
      advantages of utilizing a recently released dual lumen balloon catheter for
      ethylene vinyl alcohol copolymer, also known as Onyx (ev3, Irvine, California,
      USA), embolization for a variety of head and neck pathologies. METHODS: A
      retrospective review of all cases utilizing the Scepter C balloon catheter
      (MicroVention Inc, Tustin, California, USA) for use in balloon augmented
      embolization was performed over a 4 month period from October 2012 to February
      2013 at the Medical University of South Carolina, Charleston, South Carolina,
      USA. Charts and angiographic images were reviewed. Representative cases involving
      diverse pathologies are summarized and illustrate the observed advantages of
      balloon augmented Onyx embolization with a dual lumen balloon catheter. CASE
      ILLUSTRATIONS: Balloon augmented Onyx embolization utilizing a novel dual lumen
      balloon catheter was employed to treat both ruptured and unruptured arteriovenous
      malformations, intracranial dural arteriovenous fistulae, intracranial neoplasms,
      carotid body tumors, a thyroid mass, and an extracranial arteriovenous fistula.
      CONCLUSIONS: The dual lumen balloon catheter has several advantages for use with
      Onyx embolization over older devices, including more efficient proximal plug
      formation and enhanced navigability for placement deep within the pedicles. The
      balloon augmented Onyx embolization technique represents a valuable tool to add
      to the armamentarium of the neurointerventionalist to address a variety of head
      and neck lesions.

PMID- 24026950
TI  - Early results of the Axium MicroFX for Endovascular Repair of IntraCranial
      Aneurysm (AMERICA) study: a multicenter prospective observational registry.
AB  - BACKGROUND: Axium MicroFX coils contain polymer (polyglycolic/polylactic acid,
      PGLA) microfilaments designed to significantly impact intra-aneurysmal flow and
      to encourage aneurysm thrombosis. To provide preliminary evaluation of the safety
      and suggested efficacy of the MicroFX design, we performed a multicenter
      prospective single-arm trial, Axium MicroFX for Endovascular Repair of
      IntraCranial Aneurysm study (AMERICA). METHODS: AMERICA is a prospective
      multicenter 100 aneurysm observational study evaluating the safety and efficacy
      of Axium MicroFX PGLA coils. Enrollment was started in April 2010 and completed
      in October 2012. RESULTS: 99 patients underwent treatment for 100 aneurysms at 13
      centers. Mean age was 60.2 years, most were women (72%) and 18% of patients had
      previously undergone treatment for a separate aneurysm. 22% of patients underwent
      treatment after acute aneurysmal subarachnoid hemorrhage (SAH). Of these
      patients, all were Hunt and Hess grade 1-3. Pre-procedure modified Rankin score
      (mRS) was 0-2 in 92% of patients. The majority of aneurysms were anterior
      circulation (86%), with the most common aneurysm locations being the anterior
      communicating artery (23%) followed by the supraclinoid internal carotid artery
      and posterior communicating artery (18% each). The mean maximum diameter was 6.5
      mm. Axium MicroFX coils could be placed in all but one treatment (99%). Raymond
      grade at conclusion of coiling was I (complete) in 52%, II (dog ear or residual
      neck) in 33% and III (residual aneurysm) in 15%. Discharge mRS was significantly
      worse in patients with SAH (62% mRS 0-2) compared with electively treated
      aneurysms (mRS 0-2 in 94%, p<001). Major events were uncommon (6% thromboembolic
      events, 3% intraoperative vessel or aneurysm rupture) and device-related adverse
      events (AE) were rare (2% of cases). CONCLUSIONS: This prospective study of Axium
      MicroFX coils demonstrates excellent aneurysm occlusion rates. 52% of aneurysms
      were completely occluded post-procedure. Within the ruptured aneurysm group, post
      procedure occlusion rates were 63.6%. Major AE rates were consistent with
      historical data.

PMID- 24026953
TI  - Acetylene dithiolate linking up the [Tp'W(CO)(CN)] moiety with Ru(II) or Pd(II.).
AB  - A series of heterodinuclear complexes with acetylene dithiolate (acdt(2-) ) as
      the bridging moiety were synthesised by a facile one-pot procedure that avoided
      use of the highly elusive acetylene dithiol. Generation of the W-Ru complex
      [Tp'W(CN)(CO)(C2 S2 )Ru(eta(5) -C5 H5 )(PPh3 )] (Tp'=hydrotris(3,5
      dimethylpyrazolyl)borate) and the W-Pd complexes [Tp'W(CN)(CO)(C2 S2 )Pd(dppe)]
      and [Tp'W(CO)2 (C2 S2 )Pd(dppe)][PF6 ] (dppe=1,2-bis(diphenylphoshino)ethane),
      which exhibit a [W(eta(2) -kappa(2) -C2 S2 )M] core (M=Ru, Pd), was accomplished
      by using a transition-metal-assisted solvolytical removal of the Me3 Si-ethyl
      thiol protecting groups. All intermediate species of the reaction have been fully
      characterised. The highly coloured W-Ru complex [Tp'W(CN)(CO)(C2 S2 )Ru(eta(5) 
      C5 H5 )(PPh3 )] shows reversible redox chemistry, as does the prototype complex
      [Tp'W(CO)2 (C2 S2 )Ru(eta(5) -C5 H5 )(PPh3 )][PF6 ]. Single crystal X-ray
      diffraction and IR, EPR and UV/Vis spectroscopic studies in conjunction with DFT
      calculations prove the high electronic delocalisation of states over the acdt(2-)
      linker. Comparative studies revealed a higher donor strength and more pronounced
      dithiolate character of acdt(2-) in [Tp'W(CN)(CO)(C2 S2 )Ru(eta(5) -C5 H5 )(PPh3
      )] relative to [Tp'W(CO)2 (C2 S2 )Ru(eta(5) -C5 H5 )(PPh3 )](+) . In addition,
      the influence of the overall complex charge on the metric parameters was
      investigated by single-crystal X-ray diffraction studies with the W-Pd complexes
      [Tp'WL2 (C2 S2 )Pd(dppe)] (L=(CN(-) )(CO) or (CO)2 ). The central [W(C2 S2 )Pd]
      units exhibit high structural similarity, which indicates the extensive
      delocalisation of charge over both metals. 

PMID- 24026952
TI  - The specific role of FAM20C in amelogenesis.
AB  - Previously, we showed that Sox2-Cre;Fam20C(fl/fl) mice in which Fam20C was
      ubiquitously inactivated had severe defects in dentin, enamel, and bone, along
      with hypophosphatemia. It remains to be determined if the enamel defects in the
      mice with universal inactivation of Family with sequence similarity 20-C (FAM20C)
      were associated with the dentin defects and whether hypophosphatemia in the
      knockout mice contributed to the enamel defects. In this study, we crossed
      Fam20C(fl/fl) mice with keratin 14-Cre (K14-Cre) transgenic mice to specifically
      inactivate Fam20C in the epithelial cells, including the dental epithelial cells
      that are responsible for forming tooth enamel. X-ray, backscattered scanning
      electron microscopic, and histological analyses showed that the K14
      Cre;Fam20C(fl/fl) mice had severe enamel and ameloblast defects, while their
      dentin and alveolar bone were not significantly affected. Accordingly, serum
      biochemistry of the K14-Cre;Fam20C(fl/fl) mice showed normal phosphate and FGF23
      levels in the circulation. Analysis of these data indicates that, while FAM20C is
      a molecule essential to amelogenesis, its inactivation in the dental epithelium
      does not significantly affect dentinogenesis. Hypophosphatemia makes no
      significant contribution to the enamel defects in the mice with the ubiquitous
      deletion of Fam20C. 

PMID- 24026954
TI  - Micro-suspension coating method: a new approach in formulation and development of
      controlled porosity osmotic pump systems.
AB  - PURPOSE: The aim of this study was to design and evaluate diltiazem hydrochloride
      controlled porosity osmotic pump (CPOP) system employing a new coating technique
      named the micro suspension coating method. METHOD: In this method the fast
      dissolving pore formers were suspended in polymeric coating solution as
      micronized particles. Cellulose acetate and dextrose were used as film former
      polymer and pore former, respectively. 4 comparative parameters i. e., D24h
      (cumulative release percent after 24 h), Devzero (mean percent deviation of drug
      release from zero order kinetic), tL (lag time of the drug release) and RSQzero
      were used to assess various formulations. RESULTS: The results showed a
      significant increase of D24h due to the decrease in the thickness of the
      semipermeable membrane (SPM) and increase of the sucrose concentration (P<0.05).
      An inverse relationship was seen between sucrose amounts and drug release lag
      times of the formulations. In addition, lag time was significantly reduced
      following addition of tween 80 to SPM formulation (P<0.05). Results of scanning
      electron microscopy studies exhibited formation of pores in the membrane from
      where the drug release occurred. CONCLUSION: Micro suspension coating method was
      found to be a novel and promising method to formulate CPOP system of diltiazem
      hydrochloride.

PMID- 24026951
TI  - Cariogenic bacteria degrade dental resin composites and adhesives.
AB  - A major reason for dental resin composite restoration replacement is related to
      secondary caries promoted by acid production from bacteria including
      Streptococcus mutans (S. mutans). We hypothesized that S. mutans has esterase
      activities that degrade dental resin composites and adhesives. Standardized
      specimens of resin composite (Z250), total-etch (Scotchbond Multipurpose, SB),
      and self-etch (Easybond, EB) adhesives were incubated with S. mutans UA159 or
      uninoculated culture medium (control) for up to 30 days. Quantification of the
      BisGMA-derived biodegradation by-product, bishydroxy-propoxy-phenyl-propane
      (BisHPPP), was performed by high-performance liquid chromatography. Surface
      analysis of the specimens was performed by scanning electron microscopy (SEM). S.
      mutans was shown to have esterase activities in levels comparable with those
      found in human saliva. A trend of increasing BisHPPP release throughout the
      incubation period was observed for all materials and was more elevated in the
      presence of bacteria vs. control medium for EB and Z250, but not for SB (p <
      .05). SEM confirmed the increased degradation of all materials with S. mutans
      UA159 vs. control. S. mutans has esterase activities at levels that degrade resin
      composites and adhesives; degree of degradation was dependent on the material's
      chemical formulation. This finding suggests that the resin-dentin interface could
      be compromised by oral bacteria that contribute to the progression of secondary
      caries. 

PMID- 24026955
TI  - Reduction of coenzyme q10 content: a possible effect of isoproterenol on heart
      failure and myocardial infarction in rat.
AB  - Myocardial infarction (MI) was induced by subcutaneous injection of isoproterenol
      (ISO) to investigate the effect of ISO on Coenzyme Q10 (CoQ10) content of
      myocardium and subsequent effects on lipid peroxidation, electrocardiogram
      pattern and hemodynamic parameters of the rat's heart.36 male Wistar rats were
      divided randomly into 6 groups. To induce heart failure (HF) and MI, 10 and 100
      mg/kg of ISO was administered subcutaneously for 10 and 2 consecutive days,
      respectively. The effects of ISO on myocardium CoQ10 content, concentration of
      malondialdehyde, ECG pattern and hemodynamic parameters of heart were
      analyzed.ISO-treated rats showed significant alteration in heart hemodynamic
      parameters such as reduction of left-ventricular systolic pressure, maximum and
      minimum rate of developed left ventricular pressure, besides increase of left
      ventricular end-diastolic pressure. Significant depletion of heart CoQ10 content
      (from 4.57 and 4.55 ug/100 mg tissue in control groups to 2.85 and 2.89 ug/100 mg
      tissue in ISO-induced HF and MI groups respectively) and increase in tissue
      levels of malondialdehyde (47.1 and 53.8 nmol/100 mg tissue in ISO-induced HF and
      MI groups, respectively) were also observed in ISO-treated animals compared with
      the normal animals (17.4 and 18.8 nmol/100 mg tissue in control groups,
      respectively). Additionally CoQ10 improved ISO effects on hemodynamic parameters
      and ECG pattern in ISO-induced HF and myocardial injury.The present findings have
      demonstrated that the cardiotoxic effects of ISO such as oxidative damage and
      hemodynamic declination might be related to depletion of CoQ10 concentration.

PMID- 24026956
TI  - Spray drying as a fast and simple technique for the preparation of extended
      release dipyridamole (DYP) microparticles in a fixed dose combination (FDC)
      product with aspirin.
AB  - INTRODUCTION: Recent advances have proven that the combinational therapy of
      extended release dipyridamole (DYP) and fast release aspirin (ASP) can improve
      clinical indices of heart failure in several vascular disorders. Although
      pharmaceutical industries always supported fast, simple and cost saving
      techniques in their productions, there is no simple reported method available for
      this purpose. The aim of this study was to check the possibility of preparing a
      FDC product, containing individual dosage units of extended release DYP
      microparticles and fast release ASP, using the spray-drying technique as a
      practice compatible with pharmaceutical industries. MATERIALS AND METHOD: Solid
      dispersions of DYP in different polymeric substances (ethyl cellulose, carnauba
      wax, and Eudragit PO 100), were prepared using the spray-drying method. The
      physicochemical properties and structure of the prepared microparticles were
      analyzed using different techniques, such as the particle size analyzer (PSA),
      differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X
      ray diffraction (XRD), and USP dissolution tester. ASP tablets were prepared
      individually and tested according to pharmacopeia. RESULTS AND DISCUSSION:
      Results showed that prepared microparticles measured about 2.3 um in size.
      Statistical analysis of the release data revealed that there is no significant
      difference in the mean release amount of the selected formulation compared to the
      innovative brand (Aggrenox(r)). CONCLUSION: Findings proposed a new formulation
      (F7) as an alternative to innovative brand and proved spray drying as a practice
      compatible with pharmaceutical industries and as a successful method for
      sustaining the DYP release rate from prepared microparticles in a FDC dosage
      form.

PMID- 24026957
TI  - Development and in-vitro characterization of fish oil oleogels containing benzoyl
      peroxide and salicylic acid as keratolytic agents.
AB  - Topical keratolytic agents such as benzoyl peroxide (BP) and salicylic acid (SA)
      are one of the common treatments for inflammatory skin diseases. However, the
      amount of drug delivery through the skin is limited due to the stratum corneum.
      The purposes of this study were to investigate the ability of fish oil to act as
      penetration enhancer for topical keratolytic agents and to determine the suitable
      gelator for formulating stable fish oil oleogels. 2 types of gelling agents,
      beeswax and sorbitan monostearate (Span 60), were used to formulate oleogels. To
      investigate the efficacy of fish oil oleogel permeation, commercial hydrogels of
      benzoyl peroxide (BP) and salicylic acid (SA) were used as control, and
      comparative analysis was performed using Franz diffusion cell. Stability of
      oleogels was determined by physical assessments at 20 degrees C and 40 degrees C
      storage. Benzoyl peroxide (BP) fish oil oleogels containing beeswax were
      considered as better formulations in terms of drug permeation and cumulative drug
      release. All the results were found to be statistically significant (p<0.05,
      ANOVA) and it was concluded that the beeswax-fish oil combination in oleogel can
      prove to be beneficial in terms of permeation across the skin and stability. 

PMID- 24026958
TI  - Effects of Metoclopramide and Ranitidine on survival of flat template McFarlane
      skin flaps in a rat wound healing model.
AB  - Wound healing re-provides the morphological integrity after trauma. We
      investigated the effects of Metoclopramide and Ranitidine on survival of flat
      template McFarlane skin flaps in an experimental wound healing model.Rats (n:32)
      were randomly allocated in following groups: Flap control (Control),
      Metoclopramide(MET), Ranitidine(RAN) and Metoclopramide+Ranitidine (MET+RAN).
      After flap elevation, ip 10 mg/kg Ranitidin or 5 mg/kg Metoclopramide or the
      combination of both drugs were administered for 3 days. Next analgesia was
      maintained. No additional drugs were used for controls. On 10th day, whole cut
      skin flaps were excised, fixed in buffered formaldehyde and processed with
      histological techniques. Paraffine sections were stained with Hematoxylen-Eosin,
      Mallory-Azan and immunohistochemically with Desmin and Fibronectin and then
      evaluated with light microscopy.Experimental groups showed differences for
      epidermal degeneration, edema, hypertrophy of the hair follicles, neutrophil
      infiltration and areolar degeneration. Metoclopramide or Ranitidine
      administration positively impacts wound healing.This unique study emphasizes the
      importance of considering Metoclopramide or Ranitidine for possible adverse
      effects on flap survival in surgical clinics, therefore the combination of both
      drugs is not more effective. 

PMID- 24026959
TI  - Effect of Astragalus polysaccharides on chronic atrophic gastritis induced by N
      methyl-N'-nitro-N-nitrosoguanidine in rats.
AB  - This study investigated the effect and mechanism of Astragalus polysaccharides
      (APS) on chronic atrophic gastritis (CAG) induced by N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG) in rats. Histomorphological, hormone-level, and
      immunohistochemistry experiments were used to investigate the gastric mucosal
      injury. Pathological changes were readily found in CAG rats. Compared to the
      control rats, the CAG rats showed significantly decreased plasma levels of
      gastrin and somatostatin while their motilin levels increased. Moreover, PGE2 in
      gastric tissue increased and serum sIgA decreased significantly, while the
      GSH/GSSG ratio showed no change. Immunohistochemical detection showed that the
      expression of EGFR, COX-2, and MMP-2 was higher in the gastric tissue of CAG
      rats. After APS treatment, the gastric morphology of CAG rats improved. APS
      increased plasma gastrin and somatostatin levels significantly but had no
      significant effect on the motilin level. APS also decreased tissue PGE2 and
      increased serum sIgA in CAG rats without affecting the GSH/GSSH ratio. This study
      suggested that APS had a beneficial effect on CAG rats by deregulating EGFR at
      its downstream effectors COX-2 and MMP-2. 

PMID- 24026960
TI  - Antimicrobial glycopeptides: synthesis and antibacterial activity of N-linked and
      O-linked smaller chain glycopeptides.
AB  - Our objective is to synthesize the smaller chain N-linked and O-linked
      glycopeptides using sugars belong to mono, di and polysaccharides, with the
      efforts mainly directed towards the identification of antibacterial compounds. 7
      glycopeptides, viz., Arg-Asn-Mannose, Arg-Asn-Lactose, His-Asn-Mannose, His-Asn
      Lactose (N-glycopeptides), Arg-Ser-Lactose, Arg-Thr-Lactose, Arg-Thr-Starch (O
      glycopeptides) were prepared by dicyclohexyl carbodimide (DCC) coupling for amino
      acids using microwave oven (50W power; 15 min) and activated and coupled with
      respective sugar moieties using microwave oven at 120 W for 20-25 min. The column
      eluted compounds were tested for disc diffusion assay using 3 gram positive S.
      aureus, B. subtilis, S. caprae and 3 gram negative E. coli, P. aeruginosa and S.
      sonnei strains at different concentrations predicted by pH and inhibitory
      concentrations. One of the test glycopeptide, His-Asn-Lactose was found to be
      very effective against all the microbial strains tested and 3 other Test
      Compounds, viz., His-Asn-Mannose, Arg-Thr-Lactose and Arg-Thr-Starch are also
      proved to be effective against 2 gram positive and 2 gram negative strains
      tested. Maximum activity was observed at a concentration of 450 MUg/ml (747.51
      uM) for the N-glycopeptide His-Asn-Lactose with the corresponding zonal
      inhibition diameters (15 mm; 19 mm; 14 mm; 18 mm; 16 mm; 17 mm) against S.
      aureus, B. subtilis, S. caprae, E. coli, P. aeruginosa, S. sonnei. This is the
      first evidence based report that our N-glycopeptide, His-Asn-Lactose tested, has
      shown antibacterial action against both gram positive and gram negative strains.
      Further in vivo testing and clinical studies will make sure to position our
      potent small chain N-glycopeptide in the arsenal of new broad spectrum anti-gram
      positive and negative agent. 

PMID- 24026961
TI  - Basal insulin analogues in the management of diabetes mellitus: What progress
      have we made?
AB  - Insulin remains the most effective and consistent means of controlling blood
      glucose levels in diabetes. Since 1946, neutral protamine Hagedorn (NPH) has been
      the predominant basal insulin in clinical use. However, absorption is variable
      due to the need for resuspension and the time-action profile (peak activity 4-6 h
      after subcutaneous administration) confers an increased propensity for between
      meal and nocturnal hypoglycaemia. In the 1980s, recombinant DNA technology
      enabled modifications to the insulin molecule resulting in the soluble long
      acting insulin analogues, glargine and detemir. Both exhibit a lower risk of
      hypoglycaemia compared with neutral protamine Hagedorn due to improved time
      action profiles and reduced day-to-day glucose variability. Glargine is indicated
      for administration once daily and detemir once or twice daily. Degludec is the
      latest prolonged-acting insulin which forms long subcutaneous multi-hexamers that
      delay absorption. Recent phase III trials in type 1 and type 2 diabetes show that
      degludec was non-inferior to comparators (predominantly glargine) with a minimal
      although inconsistent reduction in overall hypoglycaemia and a small absolute
      difference in nocturnal hypoglycaemia. Newer developmental agents include
      LY2605541 and glargine U300. LY2605541 comprises insulin lispro combined with
      polyethylene glycol, thereby increasing its hydrodynamic size and retarding
      absorption from the subcutaneous tissue. Glargine U300 is a new formulation of
      glargine resulting in a flatter and more prolonged time-action profile than its
      predecessor. This article reviews recent advances in basal insulin analogues,
      including a critical appraisal of the degludec trials.

PMID- 24026962
TI  - Site-specifically arraying small molecules or proteins on DNA using an expanded
      genetic alphabet.
AB  - A class of replicable unnatural DNA base pairs formed between d5SICS and either
      dMMO2, dDMO, or dNaM were developed. To explore the use of these pairs to produce
      site-specifically labeled DNA, the synthesis of a variety of derivatives bearing
      propynyl groups, an analysis of their polymerase-mediated replication, and
      subsequent site-specific modification of the amplified DNA by Click chemistry is
      reported. With the d5SICS scaffold a propynyl ether linker is accommodated better
      than its aliphatic analogue, but not as well as the protected propargyl amine
      linker explored previously. It was also found that with the dMMO2 and dDMO
      analogues, the dMMO2 position para to the glycosidic linkage is best suited for
      linker attachment and that although aliphatic and ether-based linkers are
      similarly accommodated, the direct attachment of an ethynyl group to the
      nucleobase core is most well tolerated. To demonstrate the utility of these
      analogues, a variety of them were used to site-selectively attach a biotin tag to
      the amplified DNA. Finally, we use d5SICS(CO) -dNaM to couple one or two proteins
      to amplified DNA, with the double labeled product visualized by atomic force
      microscopy. The ability to encode the spatial relationships of arrayed molecules
      in PCR amplifiable DNA should have important applications, ranging from SELEX
      with functionalities not naturally present in DNA to the production, and perhaps
      "evolution" of nanomaterials. 

PMID- 24026963
TI  - Multicenter retrospective study of endoscopic ultrasound-guided biliary drainage
      for malignant biliary obstruction in Japan.
AB  - BACKGROUND: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is considered
      to be an effective salvage procedure for failed endoscopic retrograde
      cholangiopancreatography in patients with unresectable malignant biliary
      obstruction. The aim of this retrospective study was to evaluate the efficacy and
      feasibility of EUS-BD. METHODS: From November 2006 to May 2012, a total of 64
      patients who underwent EUS-BD (44 EUS-guided choledochoduodenostomy [EUS-CDS] and
      20 EUS-guided hepaticogastrostomy [EUS-HGS]) at seven tertiary-care referral
      centers in Japan were included. The primary outcome was the technical success
      rate, and the secondary outcomes were the incidence of complications, stent
      dysfunction rate, time to stent dysfunction, and overall survival. RESULTS: The
      technical success rate for both EUS-CDS and EUS-HGS was 95%. The reasons for
      technical failure were two failed dilations of the anastomosis in EUS-CDS and one
      puncture failure in EUS-HGS. The stent dysfunction rate and 3-month dysfunction
      free patency rate were 21% and 80% for EUS-CDS and 32% and 51% for EUS-HGS. There
      were 12 (six in EUS-CDS and six in EUS-HGS) procedure-related complications
      (19%): five cases of bile leakage (3/2), three stent misplacements (1/2), one
      pneumoperitoneum (1/0), two cases of bleeding (1/1), one perforation (1/0), and
      one biloma (0/1). Bile leakage was more frequently observed in patients who
      underwent plastic stent placement (11%) than in those with covered metal stents
      (4%). CONCLUSIONS: This Japanese multicenter study revealed a high success rate
      in EUS-BD. However, the complication rate was as high as that in previous series.
      Covered metal stents may be useful to reduce bile leakage in EUS-BD.

PMID- 24026964
TI  - Effect of continuous positive airway pressure on regional cerebral blood flow
      during wakefulness in obstructive sleep apnea.
AB  - BACKGROUND: The alteration of regional cerebral blood flow (rCBF) during
      wakefulness after the treatment for obstructive sleep apnea syndrome (OSA) using
      continuous positive airway pressure (CPAP) has not been elucidated. The aim of
      this study was to investigate rCBF characteristics and the effects of nasal CPAP
      in OSA patients. METHODS: Fifteen severe OSA patients (apnea-hypopnea index, 62.7
      +/- 22.4/h), when awake, underwent Technetium-99m ethyl cysteinate dimer single
      photon emission computed tomography before and after CPAP treatment, and the
      findings were compared to those of nine healthy controls matched for age and sex.
      RESULTS: Compared to controls, patients with OSA before CPAP treatment showed a
      significantly lower rCBF in the frontal lobe. After the treatment, no difference
      in rCBF was observed between the good CPAP compliance group and the controls. In
      the former group, there was a positive correlation between the 3% oxygen
      desaturation index on diagnostic polysomnogram and the increase of rCBF after
      CPAP treatment in the frontal lobe. CONCLUSIONS: When awake, patients with severe
      OSA were shown to have reversible decreases in rCBF, especially in the frontal
      lobe, and an appropriate CPAP treatment was thought to improve rCBF in this area.
      Our results support the importance of appropriate CPAP treatment for severe OSA
      patients.

PMID- 24026965
TI  - 1H, 15N, and 13C backbone resonance assignments for the Yersinia protein tyrosine
      phosphatase YopH.
AB  - YopH is a protein tyrosine phosphatase that functions as a required virulence
      factor in Yersinia. Here we report the backbone resonance assignments for a point
      mutant of the C-terminal catalytic domain of YopH. 

PMID- 24026966
TI  - A combination of P wave electrocardiography and plasma brain natriuretic peptide
      level for predicting the progression to persistent atrial fibrillation:
      comparisons of sympathetic activity and left atrial size.
AB  - PURPOSE: Development of atrial fibrillation (AF) is complexly associated with
      electrical and structural remodeling and other factors every stage of AF
      development. We hypothesized that P wave electrocardiography with an elevated
      brain natriuretic peptide (BNP) level would be associated with the progression to
      persistence from paroxysmal AF. METHODS: P wave electrocardiography such as a
      maximum P wave duration (MPWD) and dispersion by 12-leads ECG, heart/mediastinum
      (H/M) ratio by delayed iodine-123 metaiodobenzylguanidine scintigraphic imaging,
      left ventricular ejection fraction (LVEF), and left atrial dimension (LAD) by
      echocardiography, and plasma BNP level were measured to evaluate the electrical
      and structural properties and sympathetic activity in 71 patients (mean +/-
      standard deviation, age: 67 +/- 13 years, 63.4 % males) with idiopathic
      paroxysmal AF. RESULTS: Over a 12.9-year follow-up period, AF developed into
      persistent AF in 30 patients. A wider MPWD (>129 ms) (p = 0.001), wider P wave
      dispersion (>60 ms) (p = 0.001), LAD enlargement (>40 mm) (p = 0.001), higher BNP
      level (>72 pg/mL) (p = 0.002), lower H/M ratio (<=2.7) (p = 0.025), and lower
      LVEF (<=60 %) (p = 0.035) were associated with the progression to persistent AF,
      and the wide MPWD was an independently powerful predictor of the progression to
      persistent AF with a hazard ratio (HR) of 5.49 [95 % confidence interval (CI)
      2.38-12.7, p < 0.0001] after adjusting for potential confounding variables, such
      as age and sex. The combination of wide MPWD and elevated BNP level was additive
      and incremental prognostic power with 13.3 [2.16-13, p < 0.0001]. CONCLUSION: The
      wide MPWD with elevated BNP level was associated with the progression to
      persistent AF.

PMID- 24026967
TI  - Fibrosis and electrophysiological characteristics of the atrial appendage in
      patients with atrial fibrillation and structural heart disease.
AB  - PURPOSE: This study was conducted to investigate the degree of fibrosis in atrial
      appendages of patients with and without atrial fibrillation (AF) undergoing
      cardiac surgery. In addition, we hypothesized that areas of atrial fibrosis can
      be identified by electrogram fractionation and low voltage for potential ablation
      therapy. METHODS: Interstitial fibrosis from right (RAA) and/or left atrial
      appendages (LAA) was studied in patients with sinus rhythm (SR, n = 8),
      paroxysmal (n = 21), and persistent AF (n = 20) undergoing coronary artery bypass
      and/or aortic or mitral valve surgery. Atrial fibrosis quantification was
      performed with Masson trichrome staining. Intraoperative bipolar epicardial
      electrophysiological measurements were performed to correlate fibrosis to
      electrogram fractionation, voltage, and AF cycle length. RESULTS: The average
      degree of fibrosis was 11.2 +/- 7.2 % in the LAA and 22.8 +/- 7.6 % in the RAA (p
      < 0.001). Fibrosis was not significantly higher in paroxysmal AF patients
      compared to SR subjects (18.2 +/- 8.7 versus 20.7 +/- 5.3 %). Persistent AF
      patients had a higher degree of LAA and RAA fibrosis compared to paroxysmal AF
      patients (LAA 14.6 +/- 8.7 versus 8.6 +/- 4.7 %, p = 0.02, and RAA 28.2 +/- 7.9
      versus 18.2 +/- 8.7 %, respectively, p = 0.04). The left atrial end diastolic
      volume index was higher in persistent AF patients compared to SR controls (38.3
      +/- 16.4 and 28 +/- 11 ml/m(2), respectively, p = 0.04). No correlation between
      atrial fibrosis and electrogram fractionation or voltage was found. CONCLUSION:
      Patients with structural heart disease undergoing cardiac surgery have more
      fibrosis in the RAA than in the LAA. Furthermore, RAA fibrosis is increased in
      persistent AF but not paroxysmal AF patients compared to control subjects.
      Electrogram fractionation and low voltage did not provide accurate identification
      of the fibrotic substrate.

PMID- 24026968
TI  - Impact of nonfluoroscopic MediGuideTM tracking system on radiation exposure in
      radiofrequency ablation procedures (LESS-RADS registry)-an initial experience.
AB  - BACKGROUND: Radiation exposure in the electrophysiology (EP) lab is a major
      concern to most electrophysiologists. A new technology, MediGuideTM
      nonfluoroscopic catheter tracking system, has been used for the first time in the
      USA recently. We intended to evaluate the efficacy of this novel catheter
      tracking system in reducing radiation exposure. METHODS: We performed a
      prospective observational study by comparing the radiation exposure with
      MediGuideTM system to that of conventional mapping systems. The first 45 EP
      procedures performed with the MediGuideTM system were compared to 45 matched
      patients undergoing similar procedures during the same time frame using
      conventional mapping systems (CARTO and NavX) and fluoroscopy. We collected and
      compared baseline characteristics, procedural variables including fluoroscopic
      exposure between both groups. RESULTS: Forty-five patients underwent EP
      procedures using the MediGuideTM technology. They were matched with an equal
      number of patients with conventional mapping systems. Of the 45 patients included
      in the study, 33 underwent right atrial flutter ablations, 5 underwent
      atrioventricular nodal reentrant tachycardia ablations, 4 underwent ablation of
      Wolf-Parkinson-White syndrome, and 3 underwent EP studies with no ablation. There
      were no differences in mean age, gender distribution, and body mass index between
      the groups. Procedure duration in the MediGuideTM group was significantly lower
      than the duration in the conventional group (103 vs. 142 min, p = 0.03). The
      fluoroscopic time was significantly less during the procedures performed with the
      MediGuideTM technology when compared to the control group (8 vs. 21 min, p <
      0.001). No major complications occurred during the procedures in either group.
      CONCLUSION: MediGuideTM, a new nonfluoroscopic catheter tracking system, is
      associated with more than a 50 % reduction in fluoroscopic time when compared to
      conventional mapping systems.

PMID- 24026969
TI  - Rotors of truly atypical atrial flutters visualized by FIRM mapping and 3D-MRI
      overlay on live fluoroscopy.
AB  - Rotors of two different left atrial flutters were mapped using focal impulse and
      rotor modulation and 3D-MRI overlayed on live fluoroscopy and were successfully
      ablated in a patient with two prior left-atrium ablation procedures for recurrent
      atrial fibrillation. 

PMID- 24026970
TI  - CKD-501, a novel selective PPARgamma agonist, shows no carcinogenic potential in
      ICR mice following oral administration for 104 weeks.
AB  - CKD-501 is a peroxisome proliferator-activated receptor gamma (PPARgamma) agonist
      that is effective for the treatment of diabetes. However, its carcinogenic
      potential remains controversial. The current carcinogenicity study was conducted
      over a period of 104 weeks in ICR mice. Three groups, each consisting of 60 male
      and 60 female mice, received oral CKD-501 dosages of 0.2, 1.0 or 6.0 mg kg(-1)
      day(-1). The mortality rates of the male control, 0.2, 1.0 and 6.0 mg kg(-1) 
      day(-1) treated groups were 60%, 68%, 58% and 67%, respectively and 57%, 68% and
      67% in the female control, 0.2 and 1.0 mg kg(-1)  day(-1) treated groups. It was
      67% in the female 6.0 mg kg(-1)  day(-1) treated group, which was terminated at
      week 98 due to its increased mortality rate. No significant treatment-related
      effects were observed on the survival rates, with the exception of females in the
      6.0 mg kg(-1)  day(-1) group. Body weights increased in females receiving 1.0 and
      6.0 mg kg(-1)  day(-1) due to the class effects of the PPARgamma agonist.
      Differences were not found in hematology parameters between the CKD-501-treated
      groups and their corresponding controls, but the histopathological evidence did
      not reveal any findings attributed to CKD-501. Treated animals exhibited non
      neoplastic findings (adipocyte proliferation, bone marrow hypoplasia
      cardiomyopathy), but all of these were expected changes for this class of
      compound. There were no treatment-related neoplastic changes in this study. The
      results of this study therefore demonstrate a lack of carcinogenicity following
      oral administration of CKD-501 to ICR mice for 104 weeks.

PMID- 24026972
TI  - The adult head morphology of the hessian fly Mayetiola destructor (Diptera,
      Cecidomyiidae).
AB  - The adult head of the Hessian fly Mayetiola destructor was examined and described
      in detail. Morphological features are evaluated with respect to phylogenetic
      implications and possible effects of miniaturisation. Preserved groundplan
      features of Diptera are the orthognathous orientation of the head, the vestiture
      of small microtrichia (possible autapomorphy), filiform antennae inserted
      frontally between the compound eyes, the presence of a clypeolabral muscle
      (possible autapomorphy), the presence of labellae (autapomorphy), and the
      presence of only one premental retractor. Potential synapomorphies of the groups
      assigned to Bibionomorpha are the origin of M. tentorioscapalis medialis on the
      frons and the loss of M. craniolacinialis. Further apomorphies of Cecidomyiidae
      identified in Mayetiola are the unusually massive anterior tentorial arm, the
      absence of the labro-epipharyngeal food channel, the absence of the lacinia, and
      the presence of antennal sensilla connected by a seta, a feature not known from
      any other group of Diptera. The very large size of the compound eyes (in relation
      to the entire head surface) and the complete loss of ocelli are possible effects
      of miniaturization. The large size of the brain (in relation to the cephalic
      lumen), the unusual shape of the optic lobes, and the absence of the frontal
      ganglion as a separate structure are probably also linked with size reduction.

PMID- 24026971
TI  - Chondrogenic differentiation of ATDC5 and hMSCs could be induced by a novel
      scaffold-tricalcium phosphate-collagen-hyaluronan without any exogenous growth
      factors in vitro.
AB  - Application of chondrogenic growth factors is a routine strategy to induce
      chondrogenesis of hMSCs, but they have economic and safety problems in the long
      term. It is expected that scaffold material itself could play an important role
      in chondrogenesis of hMSCs. In this study we tested whether a novel tricalcium
      phosphate-collagen-hyaluronan scaffold (TCP-COL-HA) had inherent chondro
      inductive capacity for chondrogenesis of both ATDC5 and hMSCs without any
      exogenous growth factors in vitro. hMSCs and ATDC5 were seeded onto TCP-COL-HA
      scaffolds and cultured in basal medium for 3 weeks to investigate whether the TCP
      COL-HA scaffold itself had differentiation-inductive capacity in basal culture.
      With hMSCs-seeded scaffold in chondrogenic medium (including TGF-beta1) as
      positive control, we then compared the chondrogenic induction of TCP-COL-HA in
      basal culture and in chondrogenic culture. The chondrogenic differentiation was
      evaluated by sulfated glycosaminoglycans (GAGs) quantification, type II collagen
      immunohistochemistry, and RT-PCR. Mechanical strength was evaluated by
      compression test and the cell death rate of hMSCs was assessed with TUNEL assay.
      The results showed TCP-COL-HA scaffold itself could efficiently induce
      chondrogenic differentiation of both ATDC5 and hMSCs after 3 weeks in basal
      culture. The accumulation of GAGs and the expression of chondrocyte marker genes
      were all significantly increased. In addition, hMSCs-seeded scaffold showed a
      significantly higher mechanical strength after 3 weeks in basal culture. The
      chondrogenic induction of TCP-COL-HA scaffolds in basal medium were almost
      similar to that in chondrogenic medium on hMSCs. The chondrogenesis-inducing
      capacity of TCP-COL-HA scaffold might help to improve cartilage tissue
      engineering with economic and safe benefits.

PMID- 24026973
TI  - Emergency Care Handover (ECHO study) across care boundaries: the need for joint
      decision making and consideration of psychosocial history.
AB  - BACKGROUND: Inadequate handover in emergency care is a threat to patient safety.
      Handover across care boundaries poses particular problems due to different
      professional, organisational and cultural backgrounds. While there have been many
      suggestions for standardisation of handover content, relatively little is known
      about the verbal behaviours that shape handover conversations. This paper
      explores both what is communicated (content) and how this is communicated (verbal
      behaviours) during different types of handover conversations across care
      boundaries in emergency care. METHODS: Three types of interorganisational
      (ambulance service to emergency department (ED) in 'resuscitation' and 'majors'
      areas) and interdepartmental handover conversations (referrals to acute medicine)
      were audio recorded in three National Health Service EDs. Handover conversations
      were segmented into utterances. Frequency counts for content and language forms
      were derived for each type of handover using Discourse Analysis. Verbal
      behaviours were identified using Conversation Analysis. RESULTS: 203 handover
      conversations were analysed. Handover conversations involving ambulance services
      were predominantly descriptive (60%-65% of utterances), unidirectional and
      focused on patient presentation (75%-80%). Referrals entailed more collaborative
      talk focused on the decision to admit and immediate care needs. Across all types
      of handover, only 1.5%-5% of handover conversation content related to the
      patient's social and psychological needs. CONCLUSIONS: Handover may entail both
      descriptive talk aimed at information transfer and collaborative talk aimed at
      joint decision-making. Standardisation of handover needs to accommodate
      collaborative aspects and should incorporate communication of information
      relevant to the patient's social and psychological needs to establish appropriate
      care arrangements at the earliest opportunity.

PMID- 24026974
TI  - Type dependent patterns of human adenovirus persistence in human T-lymphocyte
      cell lines.
AB  - Disseminated adenovirus infections cause significant mortality in stem cell
      transplanted patients and are suspected to originate from asymptomatic adenovirus
      persistence ("latency") in lymphocytes. The infection of three human T-lymphocyte
      lines (Jurkat, PM1, and CEM) with human adenovirus types of species A (HAdV-A31),
      B (HAdV-B3, -B11), and C (HAdV-C2, -C5) was investigated for 150 days in order to
      establish in vitro models for adenovirus persistence. HAdV-C5 persisted with
      continuous production of infectious virus progeny (about 10(7) TCID50 /ml) in PM1
      cells. More than 100 copies of HAdV-C5-DNA per cell were detected by real-time
      PCR but hexon immunostaining showed that only 7.5% of the cells were infected
      ("carrier state infection"). Coxsackie and adenovirus receptor (CAR) expression
      was decreased in comparison to mock infected cultures suggesting selection of a
      semi-permissive subpopulation of PM-1 cells. By contrast, latency of HAdV-DNA
      (10(-3) -10(-4)  copies/cell) without production of infectious virus progeny was
      observed in HAdV-C2 infection of PM1 and Jurkat, HAdV-A31 infection of PM1, and
      HAdV-B3 infection of Jurkat cells. In addition, transcription of E1A, DNA
      polymerase and hexon mRNA was not detected by RT-PCR suggesting an equivalent of
      clinical "HAdV latency." Persistence of HAdV-DNA was not observed in abortive
      infections of PM1 cells with HAdV-B3 and -B11 and in productive, lytical
      infections of Jurkat cells with HAdV-C5, HAdV-B11, and HAdV-A31. In conclusion,
      lytic and persistent infections with and without production of infectious virus
      were observed depending on the type of adenovirus. Genetic determinants for viral
      persistence may be investigated using these newly established infection models.

PMID- 24026977
TI  - David Russell as new editor for Critical Insights to replace Carol Robinson.

PMID- 24026975
TI  - The collision cross sections of iodide salt cluster ions in air via differential
      mobility analysis-mass spectrometry.
AB  - To date, most collision cross section (CCS) predictions have invoked gas molecule
      impingement-reemission rules in which specular and elastic scattering of
      spherical gas molecules from rigid polyatomic surfaces are assumed. Although such
      predictions have been shown to agree well with CCSs measured in helium bath gas,
      a number of studies reveal that these predictions do not agree with CCSs for ions
      in diatomic gases, namely, air and molecular nitrogen. To further examine the
      validity of specular-elastic versus diffuse-inelastic scattering models, we
      measured the CCSs of positively charged metal iodide cluster ions of the form
      [MI]n[M(+)]z, where M = Na, K, Rb, or Cs, n = 1 - 25, and z = 1 - 2. Measurements
      were made in air via differential mobility analysis mass spectrometry (DMA-MS).
      The CCSs measured are compared with specular-elastic as well as diffuse-inelastic
      scattering model predictions with candidate ion structures determined from
      density functional theory. It is found that predictions from diffuse-inelastic
      collision models agree well (within 5%) with measurements from sodium iodide
      cluster ions, while specular-elastic collision model predictions are in better
      agreement with cesium iodide cluster ion measurements. The agreement with diffuse
      inelastic and specular-elastic predictions decreases and increases, respectively,
      with increasing cation mass. However, even when diffuse-inelastic cluster ion
      predictions disagree with measurements, the disagreement is of a near-constant
      factor for all ions, indicating that a simple linear rescaling collapses
      predictions to measurements. Conversely, rescaling cannot be used to collapse
      specular-elastic predictions to measurements; hence, although the precise
      impingement reemission rules remain ambiguous, they are not specular-elastic.

PMID- 24026976
TI  - Structures of a(n)* ions derived from protonated pentaglycine and pentaalanine:
      results from IRMPD spectroscopy and DFT calculations.
AB  - Infrared multiple-photon dissociation (IRMPD) spectroscopy and DFT calculations
      have been used to probe the most stable structures of a3(*) and a4(*) ions
      derived from both protonated pentaglycine (denoted G5) and pentaalanine (A5). The
      a3(*) and a4(*) ions derived from protonated A5 feature a CHR=N-CHR'- group at
      the N-terminus and an oxazolone ring at the C-terminus, as proposed previously
      [J. Am. Soc. Mass Spectrom. 19, 1788-1798 (2008)]. The isomeric a4(*) ion derived
      from A5 with a 3,5-dihydro-4H-imidazol-4-one ring structure was calculated to
      have a slightly better energy than the oxazolone, but the barrier to its
      formation is higher and there was no evidence of this ion in the IRMPD spectrum.
      By contrast, the a4(*) and [a4 - H2O](+) (denoted a4(0)) ions from G5 gave
      strikingly similar IRMPD spectra and both have the 3,5-dihydro-4H-imidazol-4-one
      ring structure similar to that recently reported for the [GGGG + H - H2O](+) ion
      [Int. J. Mass Spectrom. 316-318, 268-272 (2012)]. In the absence of a solvent
      molecule, the pathway to the oxazolone is calculated to be lower than those to
      thermodynamically more stable products, the a4(0) and the a4(*) with the 3,5
      dihydro-4H-imidazol-4-one ring structure. Incorporation of one water molecule is
      sufficient to reduce the barrier to formation of the a4(0) of G5 to below that
      for formation of the oxazolone. On the equivalent potential energy surface for
      protonated A5 the barrier to formation of the a4(0) ion is 12.3 kcal mol(-1)
      higher than that for oxazolone formation and the a4(0) ion is not observed
      experimentally.

PMID- 24026978
TI  - Structural analysis of guanylyl cyclase-activating protein-2 (GCAP-2) homodimer
      by stable isotope-labeling, chemical cross-linking, and mass spectrometry.
AB  - The topology of the GCAP-2 homodimer was investigated by chemical cross-linking
      and high resolution mass spectrometry. Complementary conducted size-exclusion
      chromatography and analytical ultracentrifugation studies indicated that GCAP-2
      forms a homodimer both in the absence and in the presence of Ca(2+). In-depth MS
      and MS/MS analysis of the cross-linked products was aided by (15)N-labeled GCAP
      2. The use of isotope-labeled protein delivered reliable structural information
      on the GCAP-2 homodimer, enabling an unambiguous discrimination between cross
      links within one monomer (intramolecular) or between two subunits
      (intermolecular). The limited number of cross-links obtained in the Ca(2+)-bound
      state allowed us to deduce a defined homodimeric GCAP-2 structure by a docking
      and molecular dynamics approach. In the Ca(2+)-free state, GCAP-2 is more
      flexible as indicated by the higher number of cross-links. We consider stable
      isotope-labeling to be indispensable for deriving reliable structural information
      from chemical cross-linking data of multi-subunit protein assemblies.

PMID- 24026979
TI  - Patient-reported outcomes for patients undergoing radical cystectomy: a
      prospective case-control study.
AB  - PURPOSE: The purpose of this study was to measure patient-reported outcomes
      (PROs) for patients with muscle-invasive bladder cancer (BC) before the diagnosis
      of BC was known, thus before cystectomy, and until 1 year postcystectomy. The
      differences in outcomes between a health status (HS) and quality of life (QoL)
      questionnaires were examined. METHODS: From July 2007 to July 2010, 598 patients
      with primary hematuria were enrolled in this prospective, multi-centre case
      control (CC) study. Patients undergoing radical cystectomy (RC; N = 18) were
      compared with patients with other causes of hematuria (CC, N = 20). Measurement
      points were before diagnosis as well as 3, 6 and 12 months postcystectomy.
      Questionnaires used were the WHOQOL-BREF, SF-12, International Index of Erectile
      Function, and 10-item STAI-Trait scale. RESULTS: Prediagnosis patients who later
      appeared to have BC had the same QoL compared to CC patients. The prediagnosis
      physical component scale of HS and sexual function were significantly lower for
      RC vs. CC patients. RC patients had a better prediagnostic QoL and HS than
      postcystectomy at all time points. CONCLUSIONS: This is the first case-control
      study with a baseline measurement of PROs before the diagnosis of BC was known.
      It shows lower physical health and sexual function for RC vs. CC before diagnosis
      is known. Until 1 year postcystectomy, QoL does not return to baseline level.
      Future studies including comorbidity and smoking history are needed to examine
      the generalizability of our results.

PMID- 24026980
TI  - Health care providers' use and knowledge of the Edmonton Symptom Assessment
      System (ESAS): is there a need to improve information and training?
AB  - OBJECTIVES: The ESAS is a clinical symptom assessment tool developed for patients
      receiving palliative care for pain and symptom control. Recent studies have
      indicated that patients have difficulty understanding terminology and correct use
      of the ESAS, and that they appreciate the presence of a health care provider
      (HCP) to assist with ESAS completion. As appropriate assessment translates into
      effective treatment, it is important that HCPs have a good understanding of the
      tool. The purpose of this study was to assess HCPs' use, knowledge, and training
      needs of the ESAS. METHODS: One hundred ninety-three HCPs in palliative care and
      chronic pain, who used the ESAS, were invited to participate in a survey.
      RESULTS: The response rate was 43 % (n = 83), with 62 % nurses, 26 % physicians,
      and 12 % other specialties. Most participants were palliative care specialists
      (79 %). The majority (77 %) had a good understanding of the ESAS terms. Knowledge
      problems included distinguishing tiredness and drowsiness (25 %), interpreting
      shortness of breath as a combination of subjective and objective symptoms (19 %),
      not indicating current symptom level (14 %), and reverse scoring of well-being
      (13 %) and appetite (9 %). Reported challenges were misinterpretation of some
      ESAS terms, assessing patients with impaired communication, and lack of time and
      reliability of caregiver assessments. Participants offered suggestions regarding
      how their knowledge and use of the ESAS could be improved. CONCLUSIONS:
      Suggestions for improving ESAS administration and training were to include term
      definitions and examples of how to ask about terms that might be challenging for
      patients. Furthermore, initial and ongoing training sessions might help to
      clarify issues with the tool.

PMID- 24026981
TI  - The symptom burden of non-small cell lung cancer in the USA: a real-world cross
      sectional study.
AB  - PURPOSE: Disease symptom management in patients with advanced non-small cell lung
      cancer (NSCLC) is a critical aspect of therapy. The main objective of our study
      was to assess patient-reported outcomes and the degree of concordance between
      physician and patient perceptions of symptom severity in advanced NSCLC in the
      USA. METHODS: Patients with advanced (stage IIIB/IV) NSCLC (N = 450) were
      recruited in a nationwide (USA) lung cancer study. Patients and their oncologists
      completed patient and physician versions of the Lung Cancer Symptom Scale (LCSS).
      Patient-reported lung cancer-specific quality of life was assessed with the
      Functional Assessment of Cancer Therapy--Lung (FACT-L). Concordance was assessed
      using the kappa-statistic. Regression analysis was performed with FACT-L total
      score as the dependent variable and patient-reported LCSS symptom scores as
      predictors. RESULTS: A high proportion of patients experienced lung cancer
      symptoms: fatigue (100 %), loss of appetite (97 %), shortness of breath (95 %),
      cough (93 %), pain (92 %), and blood in sputum (63 %). Concordance between
      physician and patients was lowest for loss of appetite (kappa 0.1701) and
      greatest for hemoptysis (kappa 0.4586). Loss of appetite (beta = -0.204; p <
      0.001), cough (beta = -0.145; p < 0.01), pain (beta = -0.265; p < 0.001), and
      shortness of breath (beta = -0.145; p < 0.01) were found to be significant
      predictors of the quality of life. CONCLUSIONS: Symptom burden in patients with
      advanced NSCLC is high and has a negative impact on the quality of life. Patient
      reported outcomes data could help optimize disease outcomes and therapy
      management in NSCLC.

PMID- 24026982
TI  - Education for cancer-related fatigue: could talking about it make people more
      likely to report it?
AB  - PURPOSE: Education-based interventions for cancer-related fatigue have shown
      promise in adults undergoing radiotherapy. Research on the cancer-related fatigue
      intervention trial (CAN-FIT) programme found that pre-radiotherapy fatigue
      information and support (pre-RFES) did not improve levels of fatigue, but was
      associated with improvements in activity-based outcomes. We aimed to measure
      whether pre-RFES resulted in greater participant self-ratings of their
      performance of daily living activities, fatigue, quality of life and distress.
      METHODS: Thirty people undergoing radiotherapy and/or chemotherapy were randomly
      allocated to either a 1-h RFES session from the CAN-FIT programme (delivered
      individually to participants and modified where necessary for patients undergoing
      chemotherapy) or standard care. Measures were taken pre- and post-treatment and 6
      weeks after completing treatment. RESULTS: There was no significant difference
      between groups on performance of daily living activities or ratings of distress.
      Further analysis found a significant difference between the control and treatment
      groups for EQ-5D health state visual analogue scale (-9.05 [-18.09; -0.018]; p <
      0.05) and physical fatigue (2.86 [0.58; 5.14]; p < 0.02) with the treatment group
      rating their overall health state worse and their physical fatigue higher than
      the controls. CONCLUSIONS: Pre-RFES delivered individually did not significantly
      improve participants' ratings of their performance of daily occupations and was
      unexpectedly associated with worse overall health state and higher physical
      fatigue. Future trials, ideally comparing individual and group education to
      exercise programmes or cognitive-behavioural approaches, are recommended to
      examine the broader question of whether discussing fatigue might actually make
      participants feel worse.

PMID- 24026983
TI  - Antiemetic prescribing practices using a computerized physician order entry
      system.
AB  - PURPOSE: Adherence to guideline-consistent chemotherapy-induced nausea and
      vomiting (CINV) prophylaxis is suboptimal. The primary aim of this study was to
      evaluate the magnitude of compliance to institutional guideline-directed
      antiemetic prophylaxis using a computerized physician order entry system at a
      single tertiary care institution. A nurse survey was also performed to evaluate
      how oncology practices, within a cooperative group, managed clinician orders for
      the prevention of CINV. METHODS: The electronic medical records of 100
      consecutive patients were evaluated. The primary endpoint was the incidence of
      compliance to provide all aspects of scheduled institutional guideline-directed
      antiemetic prophylaxis for acute (day 1) and delayed (days 2-4) CINV. A
      descriptive analysis was performed on the convenience sample. Logistic regression
      was completed to determine the predictors of noncompliance. RESULTS: The
      incidence of compliance on days 1-4 was 94 %. Half of the noncompliant events
      (three of six, 50 %) occurred on day 1 alone and involved patients receiving low
      emetogenic chemotherapy. There was a high degree of compliance to institutional
      guidelines for the treatment of delayed CINV (97 %). Patients receiving minimally
      emetogenic and moderately emetogenic chemotherapy (N = 70) were observed to be
      100 % compliant. Patients receiving doxorubicin/cyclophosphamide were numerically
      less likely to receive institutional guidelines, compared to patients receiving
      other chemotherapy regimens (OR, 0.24 (0.04, 1.36), p value, 0.05). The nurse
      survey suggested significant variability amongst the involved institutions with
      regards to antiemetic prescribing practices. CONCLUSIONS: Computerized physician
      order entry is associated with impressive adherence to clinician-prescribing
      practices, according to institutional guidelines, for acute and delayed CINV.

PMID- 24026984
TI  - Mechanistic modeling of sulfur-deprived photosynthesis and hydrogen production in
      suspensions of Chlamydomonas reinhardtii.
AB  - The ability of unicellular green algal species such as Chlamydomonas reinhardtii
      to produce hydrogen gas via iron-hydrogenase is well known. However, the oxygen
      sensitive hydrogenase is closely linked to the photosynthetic chain in such a way
      that hydrogen and oxygen production need to be separated temporally for sustained
      photo-production. Under illumination, sulfur-deprivation has been shown to
      accommodate the production of hydrogen gas by partially-deactivating O2 evolution
      activity, leading to anaerobiosis in a sealed culture. As these facets are
      coupled, and the system complex, mathematical approaches potentially are of
      significant value since they may reveal improved or even optimal schemes for
      maximizing hydrogen production. Here, a mechanistic model of the system is
      constructed from consideration of the essential pathways and processes. The role
      of sulfur in photosynthesis (via PSII) and the storage and catabolism of
      endogenous substrate, and thus growth and decay of culture density, are
      explicitly modeled in order to describe and explore the complex interactions that
      lead to H2 production during sulfur-deprivation. As far as possible, functional
      forms and parameter values are determined or estimated from experimental data.
      The model is compared with published experimental studies and, encouragingly,
      qualitative agreement for trends in hydrogen yield and initiation time are found.
      It is then employed to probe optimal external sulfur and illumination conditions
      for hydrogen production, which are found to differ depending on whether a maximum
      yield of gas or initial production rate is required. The model constitutes a
      powerful theoretical tool for investigating novel sulfur cycling regimes that may
      ultimately be used to improve the commercial viability of hydrogen gas production
      from microorganisms.

PMID- 24026987
TI  - Assessment of contrast sensitivity and aberrations after photorefractive
      keratectomy in patients with myopia greater than 5 diopters.
AB  - This study aimed to assess changes in contrast sensitivity and aberrations in
      cases of myopia greater than 5.0 diopter (D) who had photorefractive keratectomy
      (PRK). In this semi-experimental study, 20 eyes of ten patients were studied.
      Inclusion criteria were at least 5.0 D of myopia, stable refraction in the past
      year, no history of refractive surgery, a minimum corneal thickness of 480 MUm,
      and having surgery in both eyes. Exclusion criteria were the presence of any
      corneal condition. In addition to the routine tests, aberrometry and assessment
      of contrast sensitivity was done using the WaveLight Allegro Analyzer and the
      VectorVision CSV-1000. After PRK using the Concerto Excimer Laser (WaveLight,
      Alcon), patients were scheduled to have follow-up visits at 1 month, 3 months,
      and 1 year after surgery. Contrast sensitivity with glare showed an increasing
      trend only at the spatial frequency of 3 cycles per degree (cpd) (P=0.013).
      Contrast sensitivity without glared increased postoperatively at special
      frequencies of 3, 6, and 18 cpd (P<0.05). The preoperative level of higher order
      aberrations root mean square (HOA RMS) of 0.24+/-0.08 reached 0.71+/-0.25 at 12
      months after surgery. Assessment of comma and trefoil showed no significant
      difference between preoperative and postoperative values, but the amount of
      spherical aberration changed from a mean preoperative value of 0.0+/-0.09 to
      0.27+/-0.15 at 12 months after surgery. In the treatment of myopia greater than
      5.0 D, PRK with the Concerto Excimer Laser can improve contrast sensitivity in
      certain spatial frequencies. This is while HOA RMS and spherical aberration
      increase. 

PMID- 24026988
TI  - Correlation of preoperative sinusitis patients' characteristics with final
      diagnostic findings.
AB  - Chronic rhinosinusitis (CRS) is a common disease which is usually diagnosed
      clinically, considering the combination of natural history, physical examination
      and imaging studies. This study aimed to evaluate the clinical value of routine
      postoperative histopathologic examination (POHE) in patients with a clinical
      diagnosis of chronic rhinosinusitis with polyposis (CRSWP), or without polyposis
      (CRSWOP One hundred of patients with clinically approved CRSWP and CRSWOP were
      enrolled in this study. All patients underwent complete physical examination,
      scoring paranasal sinuses involvement by Lund-Mackay (LM) CT scoring scale,
      determining the extent of polyposis by Stumberger's endoscopic classification,
      and assessing health related quality of life by Sinonasal Test 22 (SNOT22)
      questionnaire. After FESS, histopathologic results were compared with
      preoperative clinical diagnosis. Among our patients, 65% were male, and the rest
      of them were female. Also, 66% of them suffered from CRSWP, and the rest of them
      were CRSWOP. LM CT score and SNOT22 score was 36.62+/-12, 17.11+/-6, and 43.62+/
      20 respectively. Only in one of patients with CRSWP, POHE was other than what was
      expected preoperatively (adenoid cystic carcinoma). In all other cases,  POHE was
      well correlated with preoperative clinical diagnosis. HRQOL was better in males,
      absence of septal deviation and CRSWOP (P<0.05). Para nasal sinuses involvement
      in preoperative CT was more severe in the presence of eosinophil in POHE
      (P=0.008) and in patients with class 3 Stumberger's classification (P<0.001).
      This study suggested preoperative clinical diagnosis of CRS considering the
      combination of natural history, physical examination and imaging studies can be
      accurate, and POHE is indicated only in suspicious cases. 

PMID- 24026985
TI  - Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in
      the BBSome subunit BBIP1 (BBS18).
AB  - BACKGROUND: Bardet-Biedl syndrome (BBS) is a recessive and genetically
      heterogeneous ciliopathy characterised by retinitis pigmentosa, obesity, kidney
      dysfunction, postaxial polydactyly, behavioural dysfunction and hypogonadism. 7
      of the 17 BBS gene products identified to date assemble together with the protein
      BBIP1/BBIP10 into the BBSome, a protein complex that ferries signalling receptors
      to and from cilia. METHODS AND RESULTS: Exome sequencing performed on a sporadic
      BBS case revealed for the first time a homozygous stop mutation (NM_001195306:
      c.173T>G, p.Leu58*) in the BBIP1 gene. This mutation is pathogenic since no BBIP1
      protein could be detected in fibroblasts from the patient, and BBIP1[Leu58*] is
      unable to associate with the BBSome subunit BBS4. CONCLUSIONS: These findings
      identify BBIP1 as the 18th BBS gene (BBS18) and suggest that BBSome assembly may
      represent a unifying pathomechanism for BBS.

PMID- 24026989
TI  - Radiofrequency uvulopalatoplasty for primary snoring.
AB  - Simple snoring is a social problem, one that can gravely affect the patient's
      married life. About 40% of men and 20% of women are affected, and it often goes
      along with sleep-disordered breathing. Up to now various surgical techniques have
      been defined such as UPPP(uvulopalatopharyngo plasty), and laser-assisted
      uvulopalatoplasty (LAUP). Among the surgical methods, RAUP (radiofrequency
      assisted uvulopalatoplasty) is a minimal invasive, an easy performed, and time
      and cost effective one. We designed a before and after a clinical trial. The
      inclusion criteria were age >18 years, complaint of nocturnal snoring, have a bed
      partner to assess snoring, AHI<5 events per hour in the polysomnography,
      malampathy score (soft palate position) I or II, an elongated uvula, grade I and
      II of pharyngeal webbing and patient consent was needed too. A 10-score visual
      analog scale (VAS) of snoring severity was completed by bed partner. All of 35
      included patients underwent RAUP under local anesthesia by the same expert
      surgeon. After 3 months, 6 months and one year, subjective snoring decreased
      significantly compared to the preoperative period. The decline in VAS in 6 month
      compared to 3 months postoperatively, was not significant (P=0.223). When
      comparing 1 year and 6 months after treatment, the VAS scores were increased, but
      they were not significant (From 1.8 to 1.9, P=0.78). Three months after treatment
      minor complications consisted of: nasal regurgitation in 2 patients (5.7%), nasal
      speech in 2 (5.7%) and exacerbation of snoring in 2 (5.7%) patients.There was no
      major complication including mucosal laceration, uvular damage and obstruction of
      the airway. The rate of snoring decrease did not correlate with age, sex and BMI.
      Based on this study and literature review, it seems RAUP is a safe surgery, which
      may decrease symptoms of snoring, at least, in short-term follow-up.

PMID- 24026990
TI  - The evaluation of perioperative safety of local anesthesia with lidocaine
      containing epinephrine in patients with ischemic heart disease.
AB  - The use of local anesthesia with lidocaine containing epinephrine in patients
      with cardiac disease is controversial in the literature. The aim of our study was
      determining the safety of use the local anesthesia contain epinephrine in
      patients with ischemic heart disease that undergoing reconstructive surgery.
      Thirty two patients that had known ischemic heart disease and candidate to
      undergo reconstructive surgery for skin tumor enrolled in this study.  All
      patients continued their medication for cardiac disease till morning of the
      operation. 10 ml lidocaine 2% containing 1:100,000 epinephrine was injected in
      patients for local anesthesia. The hemodynamic changes and electrocardiographic
      variables before injection were compared with them after injection, during
      surgery and till 6 hours postoperation period. A 12 lead electrocardiogram was
      recorded in all our cases for detection of myocardial ischemic changes. The mean
      age, weight and height were 58.2+/-10.4, 74.8.+/-14.4 kg and 164.5+/- 8 cm
      respectively. Twelve patients (37.5%) were diagnosed with systemic hypertension
      and 10 patients with diabetes (31.2%). The comparison of change of systolic,
      diastolic and mean blood pressure between baseline, during procedure and after
      operation defined that our subjects did not have any significant disturbance in
      blood pressure in perioperative period. The comparison of baseline heart rate
      with heart rate after injection, during procedure and in postoperation period
      indicated a significant changes in this variable (P=0.044). The heart rhythm
      during the perioperative period also failed to exhibit alterations. The ischemic
      change was not recorded in our patients before injection compared to after
      injection. None of our patients have any early complications because of
      infiltration of local anesthetic containing epinephrine in our patients. The use
      of 10 ml 2% lidocaine with epinephrine 1:100,000 in patients with cardiac disease
      represent a safe anesthetic procedure. These patients experienced a more profound
      anesthesia with hemodynamic stability and without myocardial ischemic changes. 

PMID- 24026991
TI  - Evaluation of low level laser therapy in reducing diabetic polyneuropathy related
      pain and sensorimotor disorders.
AB  - Over the past three decades physicians have used light level laser therapy (LLLT)
      for the management and the treatment of diabetic peripheral neuropathy and have
      obtained results that calls for further investigations. This study aimed to
      investigate the effectiveness of LLLT in treatment of pain symptoms in patients
      with diabetic polyneuropathy. In this study 60 patients with diabetic peripheral
      neuropathy were matched based on their sex, age, BMI, type of diabetes, duration
      of diabetes, and duration of pain, and randomized to case and control groups
      based on their established scores on the visual analog scale (VAS) and the
      Toronto clinical scoring system (TCSS). Cases received laser therapy with
      wavelength of 78 nm and 2.5 j/cm2 two times a week, each time for 5 min, for one
      month. During the same period, controls received sham laser therapy. Comparing
      the differences between the two groups' VAS and TCSS mean scores before the
      intervention with that of the 2 weeks and 4 weeks after the intervention we were
      able to see a statistically significant difference between the two groups
      (P<0.05). On the other hand, when we compared their VAS and TCSS mean scores 4
      weeks and 2 weeks after the intervention we did not find any statistically
      significant difference between the two groups. We achieved the same results when
      we examined cases' and controls' pre and post VAS and TCSS scores independent
      from each other; no improvement in the assessment based on their 2 and 4 weeks
      comparisons tests. Laser therapy resulted in improved neuropathy outcomes in
      diabetic patients who received it relative to the group that received sham
      therapy, evaluating before and after LLLT assessments. Further studies are needed
      to test types of lasers, as well as different dosage and exposure levels required
      in different phase of neuropathic care, so as to obtain reproducible results. 

PMID- 24026986
TI  - P53 but not cyclin E acts in a negative regulatory loop to control HER-2
      expression in MCF-7 breast carcinoma cell line.
AB  - Cyclin E, HER-2 and p53, are considered as major prognostic markers in breast
      cancer. As they are related in patho-clinical level, we aimed to check if they
      have any direct interaction on expression of each other. To study the effect of
      cyclin E on HER-2 expression, cell lines stably overexpressing cyclin E or its
      low molecular weight (LMW) isoforms were generated. To understand the results of
      p53 silencing either alone or in combination with cyclin E overexpression, we
      created three different p53 stably knocked down cell lines. Protein expression
      was analyzed by western blot, HER-2 expression in the established cell lines were
      determined using SYBR green real time PCR and data analyzed by REST software.
      Results indicate that HER-2 expression is only downregulated following p53
      silencing and none of cyclin E isoforms can alter its expression. The presence of
      cyclin E isoforms in p53 silenced clones also does not altered HER-2 expression.
      Given the fact that p53 degradation is increased by HER-2 overexpression, these
      data can draw a regulatory loop in which a non-mutated functional p53 and HER-2
      can bidirectionally regulate the expression of these two genes. This study
      improves our understandings of these pathways and these proteins can be
      introduced either as a marker or as a target in cancer treatment. 

PMID- 24026992
TI  - Developing SNOMED-CT for decision making and data gathering: a software prototype
      for low back pain.
AB  - The issue of medical errors is currently a global concern which places a heavy
      financial and emotional burden on communities. A clinical decision support system
      (CDSS) is an electronic system designed to support clinical decision making.
      Considering the increasing importance and use of Systematized Nomenclature of
      Medicine-Clinical Terms (SNOMED-CT), we developed SNOMED-CT to implement it more
      efficiently in making smart history taking, decisions to perform lab tests and
      imaging, diagnosis and recommendations. To evaluate these capabilities in real
      clinical problems, a new CDSS was compiled, aimed at supporting decisions on
      patients with a chief complaint of low back pain (LBP). A number of LBP
      differential diagnoses as well as some recommended indications and
      contraindications published by guidelines, were inputted to the database. Future
      software based on this model would help physicians to do necessary assessments
      and recommendations and might improve patients' safety. 

PMID- 24026993
TI  - Association of haptoglobin phenotypes with clinical features of preterm labor
      disease.
AB  - Preterm birth means the birth before thirty seven week of pregnancy that causes a
      lot of complications for the baby. Variety factors are suggested to be involved
      in disease. In this study, we decided to evaluate haptoglobin (Hp) phenotypes
      association with clinical features of patients suffered from premature delivery
      to understand better the possible correlation of genetic and clinical features in
      this disease. This cross sectional analytic descriptive study has been carried
      out in two groups of 120 women, 60 with preterm and 60 with term labor. Patients
      were selected with previously diagnosed by a gynecologist with preterm birth in
      hospital during the study period. After performing diagnostic tests, the
      frequency of each haptoglobin phenotype in the two groups was analyzed using the
      X2 test and SPSS software. The maximum serum haptoglobin phenotype frequency in
      patients with Hp2-2, was 43 (71.7%) whereas in healthy individuals, 35 (58.3%).
      No statistically significant differences between the two groups was found
      (P=0.310). But based on some patients clinical features such as their history of
      preterm delivery, previous history of recurrent abortions and history of preterm
      delivery in their family, significant association was found with Hp2-2 compared
      with healthy control (P<0.003). This study showed that Hp2-2 phenotypes levels in
      the case group was higher than in control but the factors influencing the
      presence or absence of preterm labor is clinically various. 

PMID- 24026994
TI  - Triple-negative breast cancer survival in Iranian patients.
AB  - This study focused on triple-negative breast cancer (TNBC) that is characterized
      by the lack of expression of estrogen receptor (ER), progesterone receptor (PR),
      and human epidermal growth factor receptor 2 (HER-2). The primary goal of this
      study was to describe the relation between triple-negative receptor status and
      survival. This is the first study about triple-negative breast cancer in our
      community of the 1541 patients diagnosed with breast cancer between 2002 and 2007
      at the Cancer Institute (Tehran, Iran). 107 patients were identified as TNBC and
      107 patients were randomly selected as non-TNB. HER-2, ER and PR status were
      assessed by immunohistochemistry (IHC). Analyses of their collected data were
      performed retrospectively and then clinical and pathologic parameters were
      compared between two groups. In multivariate analysis, a significantly decreased
      overall survival was observed for patients with TNBC compared with non-TNBC (55.7
      months versus 60.7 mounts; 95%CI: 51.1-60.3 and 57.9-63.5 for TNBC and non-TNBC
      respectively, P=0.0008). The 2- and 5-year estimates for overall survival were
      69.8% and 62.3% for TNBC, and 90% and 83% for non-TNBC, respectively. During the
      study period, 36 (33.6%) patient of TNBC and 14 (13.1%) of non-TNBC presented
      local recurrence. Significantly decreased disease-free survival was also observed
      for patients with TNBC compared with non-TNBC (P=0.0004). The 2- and 5-year
      estimates for disease-free survival were 68% and 63% for TNBC; and 89% and 82%
      for non-TNBC, respectively. Significantly decreased distant metastasis free
      survival was also observed for patients with TNBC compared with non-TNBC (54.4
      mounts versus 61.7 mounts; 95%CI: 49.8-59.0 and 59.1-64.4 for TNBC and non-TNBC
      respectively, P=0.0004). Triple negative breast cancer has a biologic aggressive
      behavior and poor prognosis. Therefore aggressive treatment and regular follow-up
      in early stage of diagnosis can be a significant impact on their prognosis. 

PMID- 24026995
TI  - Insulin refusal in Iranian patients with poorly controlled type 2 diabetes
      mellitus.
AB  - To achieve tight glycemic control in diabetic patients, it may be necessary to
      introduce insulin therapy much earlier in the disease course. Poor glycemic
      control is a risk factor for the development of diabetic complications. Many
      patients require insulin therapy after several years of disease in order to
      maintain good glycemic control and prevent complications. But many patients do
      not receive insulin therapy in a timely manner because of a negative appraisal of
      this treatment. Understanding the cause of this negative attitudes is necessary
      for better evaluation to overcome for this problem. The purpose of this study was
      to evaluate the reasons for insulin refusal among patients with type 2 diabetes.
      This is a descriptive cross-sectional study from Yazd Diabetes Research Center.
      400 patients with type 2 diabetes who had an HbA1c >=8.0% despite optimal oral
      therapy were identified that participated in this study. Data were obtained by
      patient interview using validated questionnaires. This study showed that Insulin
      refusal was common. 77% of participant reported being unwilling to take insulin
      if prescribed. Fear of injection is an important cause for insulin refusal among
      patients. Insulin refusal is an important problem among our patients with type 2
      diabetes mellitus. Findings of this study suggest that interventions aimed at
      increasing insulin use should focus on injection-related concerns, education and
      correction of misconceptions.

PMID- 24026996
TI  - Bilateral primary breast lymphoma in a teenage girl with multi-organ involvement.
AB  - We present 16 years old girl with primary breast lymphoma involving the both
      breasts simultaneously and co-incidence of central nervous system (CNS)
      involvement which originated from the breast, in addition to evidence of lymphoma
      in multi-organ such as skin, mediastinum and some abdominal viscera. Bilaterality
      has been observed in some series, but reports are few and series are often very
      small. Radiologic features may be indistinguishable from those of the other
      breast malignancies, but it can be concluded that primary involvement of the
      breast with lymphoma should be considered when breast mass or inflammatory
      changes occur in a patient without any previously diagnosed lymphoma. The
      clinical behavior, imaging and therapeutic procedures are discussed. The findings
      of this report may have clinical impact on oncologists or that may alter the
      disease concept of bilateral breast lymphoma. 

PMID- 24026997
TI  - Safety and effectiveness of combined percutaneous coronary angioplasty and aortic
      valvuloplasty in an elderly patient with cardiogenic shock: effect on concomitant
      severe mitral regurgitation.
AB  - An 80-year-old diabetic man with severe aortic stenosis was admitted to our
      hospital for cardiogenic shock complicating non-ST-elevation myocardial
      infarction. Echocardiographic evaluation showed also a severe degree of both left
      ventricular dysfunction and mitral regurgitation. The patient was initially
      stabilized with inotropes and mechanical ventilation was necessary because of
      concurrent pulmonary edema. The day after, he was submitted to coronary
      angiography showing bivessel coronary disease. Given the high estimated operative
      risk, the patient was treated with angioplasty and bare metal stent implantation
      on both right coronary and circumflex artery; contemporarily, balloon aortic
      valvuloplasty (BAV) was performed with anterograde technique, obtaining a
      significant increase in planimetric valve area and reduction in transvalvular
      peak gradient. Few days after the procedure echocardiogram showed an increase in
      left ventricular ejection fraction, moderate aortic stenosis with mild
      regurgitation and moderate mitral regurgitation. Hemodynamic and clinical
      stabilization were also obtained, allowing amine support discontinuation and
      weaning from mechanical ventilation. At three months follow-up, the patient
      reported a further clinical improvement from discharge, and echocardiographic
      evaluation showed moderate aortic stenosis and an additional increase in left
      ventricular function and decrease in mitral regurgitation degree. In conclusion,
      combined BAV and coronary angioplasty were associated in our patient with
      hemodynamic and clinical stabilization as well as with a significant reduction in
      transvalvular aortic gradient and mitral regurgitation and an increase in left
      ventricular ejection fraction both in-hospital and at three month follow-up; this
      case suggests that these procedures are feasible even in hemodynamically unstable
      patients and are associated with a significant improvement in quality of life. 

PMID- 24026998
TI  - Intra-abdominal desmoplastic small round cell tumor in a 45-year-old man: a case
      report.
AB  - Intra-abdominal desmoplastic small round cell tumor is a rare entity with a few
      reports worldwide. This tumor commonly occurs in children and adolescent and
      occurrence in adult age group is very rare. Here, we describe an adult male with
      symptoms of intestinal obstruction due to abdominal mass, located in splenic
      flexure. After resection, the diagnosis of intra-abdominal desmoplastic small
      round cell tumor was established by pathologic and immunohistochemical studies.
      We emphasize that albeit being rare, this tumor should be mentioned as one of the
      differential diagnoses of widespread intra-abdominal lesions in any age group.  A
      brief review of epidemiology, clinical manifestations as well as pathological and
      molecular features is also included in the paper. 

PMID- 24026999
TI  - Disseminated tuberculosis in an AIDS/HIV-infected patient.
AB  - Disseminated tuberculosis (TB) is commonly seen in HIV-infected patients and is
      major cause of death in these patients. In HIV-infected patients disseminated
      tuberculosis is frequently undiagnosed or misdiagnosed. In this article we report
      a case of disseminated TB in a HIV-infected patient with a relatively long
      history of fever and other complaints without definite diagnosis. Diagnosis of
      disseminated TB was confirmed by bone marrow biopsy and polymerase chain reaction
      analysis (PCR) of the ascitic fluid. With anti-TB treatment signs and symptoms
      improved. 

PMID- 24027000
TI  - When do we start Basso, Beattie, and Bresnahan assessment after experimental
      spinal cord injury?

PMID- 24027002
TI  - Cleavage of P=O in the presence of P-N: aminophosphine oxide reduction with in
      situ boronation of the P(III) product.
AB  - In contrast to tertiary phosphine oxides, the deoxygenation of aminophosphine
      oxides is effectively impossible due to the need to break the immensely strong
      and inert P?O bond in the presence of a relatively weak and more reactive P?N
      bond. This long-standing problem in organophosphorus synthesis is solved by use
      of oxalyl chloride, which chemoselectively cleaves the P?O bond forming a
      chlorophosphonium salt, leaving the P?N bond(s) intact. Subsequent reduction of
      the chlorophosphonium salt with sodium borohydride forms the P(III)
      aminophosphine borane adduct. This simple one-pot procedure was applied with good
      yields for a wide range of P?N-containing phosphoryl compounds. The borane
      product can be easily deprotected to produce the free P(III) aminophosphine.
      Along with no observed P?N bond cleavage, the use of sodium borohydride also
      permits the presence of ester functional groups in the substrate. The
      availability of this methodology opens up previously unavailable synthetic
      options in organophosphorus chemistry, two of which are exemplified. 

PMID- 24027001
TI  - Enhanced insulin action following subcutaneous co-administration of insulin and C
      peptide in rats.
AB  - BACKGROUND: This study was undertaken to examine if C-peptide (C) may interact
      with hexameric insulin and facilitate its disaggregation into the physiologically
      active monomeric form. METHODS: Regular insulin (I) or an insulin analogue (IA)
      were injected s.c. in rats together with C or its C-terminal pentapeptide (PP). I
      or IA and C or PP were administered either as a physical mixture or into two
      separate s.c. depots. Whole body glucose utilization was evaluated using the
      euglycemic clamp technique. Phosphorylation of Akt/PKB and GSK in liver and
      skeletal muscles and 86Rb+ uptake by L6 cells were measured. RESULTS: S.c.
      injection of a mixture of I and C or I and PP resulted in a 30-55% greater (P <
      0.01-0.001) and 15-27% (P < 0.05-0.001) longer stimulation of whole body glucose
      utilization than after separate injections. Insulin-stimulated phosphorylation of
      Akt/PKB in liver increased 35% more after injection of I and C in mixture
      compared with after separate injections. Phosphorylation of GSK3 was augmented by
      50% (P < 0.05) following the injection of I and C in mixture compared with
      separate injections. Stimulation of myotubes with premixed I and C (1 nM)
      elicited 20% additional increase in ouabain-sensitive 86Rb+ uptake (P < 0.05) in
      comparison with the effect when I and C were added separately. CONCLUSIONS:
      Subcutaneous co-administration of insulin and C results in augmented insulin
      bioactivity at the level of tissue glucose uptake, intracellular signalling, and
      enzyme activation. These effects may be attributed to augmented C mediated
      disaggregation of hexameric insulin into its physiologically active monomeric
      form.

PMID- 24027003
TI  - Synthesis of silicon-functionalized dibenzosilaborins by intramolecular B-H/C-H
      dehydrogenative cyclization and their tunable photophysical and chemical
      properties by silyl groups.
AB  - A bit borane: Silicon-functionalized dibenzosilaborins were prepared by
      intramolecular B-H/C-H dehydrogenative cyclization of o
      (silyl)(hydroboryl)benzenes. The hydrosilyl derivative (X=H) can be converted
      into the fluorosilane (X=F) and chlorosilane (X=Cl). UV/Vis and fluorescence
      spectra are influenced by the functional groups X on the silicon atom through
      sigma*-pi* conjugation.

PMID- 24027004
TI  - Neuro-ophthalmic deficits after head trauma.
AB  - Head trauma can injure the afferent and/or efferent visual systems, resulting in
      neuro-ophthalmic deficits. When assessing afferent pathway injuries, a stepwise
      approach to evaluating visual acuity, pupils, color perception, and visual fields
      is critical. Traumatic optic neuropathy is of especial importance and its
      management must be tailored on a case-by-case basis. Efferent pathway injuries
      should be assessed with attention to abnormalities of ocular alignment and
      motility, which may occur as isolated deficits or as part of a recognizable
      syndrome. Concussion or diffuse axonal injuries may also affect ophthalmologic
      function. Here, we review the extant literature describing the assessment and
      acute treatment of traumatic neuro-ophthalmic deficits. 

PMID- 24027006
TI  - Spinocerebellar ataxia type 10: from Amerindians to Latin Americans.

PMID- 24027005
TI  - Monoclonal antibodies as disease modifying therapy in multiple sclerosis.
AB  - Multiple sclerosis (MS), a demyelinating disease of the central nervous system,
      was untreatable until the mid-1990s when beta-interferons and glatiramer acetate
      were introduced. These agents, while effective, were relatively nonspecific in
      action. Over the last 10 years, research has focused toward developing more
      targeted therapies for the disease. Monoclonal antibodies (mAbs) have been
      central to these efforts and many of the mAbs studied in MS have been singularly
      effective. We review here the 6 monoclonal antibodies that have been approved for
      MS or are in late-stage clinical trials, focusing on the drugs' efficacy and
      safety. Additionally, we review several monoclonal antibodies that were studied
      in MS but were found to be ineffective or even deleterious in this patient
      population.

PMID- 24027007
TI  - Towards a clearer definition of logopenic progressive aphasia.
AB  - Logopenic progressive aphasia is the most recently described clinical variant of
      primary progressive aphasia (PPA), defined by impairment of lexical retrieval and
      sentence repetition. Unlike other PPA variants, the logopenic variant of PPA (lv
      PPA) is commonly associated with Alzheimer's disease (AD), a fact that is
      relevant to the selection of patients for clinical trials and disease-modifying
      therapies. Despite the straightforward definition and coherent pathological
      association, the existence of lv-PPA has been challenged, as its distinction from
      AD or other PPA variants can be difficult. Despite these issues, lv-PPA patients
      display characteristic linguistic deficits, a pattern of brain atrophy, and
      possibly genetic susceptibility, which warrant considering this variant as a
      discrete AD endophenotype. More specific clinical and anatomical markers can
      strengthen the consistency of this syndrome. 

PMID- 24027010
TI  - The nonsingularity of gamma in covariance structure analysis of nonnormal data.
AB  - Covariance structure analysis of nonnormal data is important because in practice
      all data are nonnormal. When applying covariance structure analysis to nonnormal
      data, it is generally assumed that the asymptotic covariance matrix Gamma for the
      nonredundant terms in the sample covariance matrix S is nonsingular. It is shown
      this need not be the case, which raises a question of how restrictive this
      assumption may be and how difficult it may be to verify it. It is shown that
      Gamma is nonsingular whenever sampling is from a nonsingular distribution,
      including any distribution defined by a density function. In the discrete case
      necessary and sufficient conditions are given for the nonsingularity of Gamma,
      and it is shown how to demonstrate Gamma is nonsingular with high probability.
      Thus, the nonsingularity of Gamma assumption is mild and one should feel
      comfortable about making it. These observations also apply to the asymptotic
      covariance matrix Gamma that arises in structural equation modeling. 

PMID- 24027009
TI  - Inactivation of DNA mismatch repair by variants of uncertain significance in the
      PMS2 gene.
AB  - Lynch syndrome (LS) is a common cancer predisposition caused by an inactivating
      mutation in one of four DNA mismatch repair (MMR) genes. Frequently a variant of
      uncertain significance (VUS), rather than an obviously pathogenic mutation, is
      identified in one of these genes. The inability to define pathogenicity of such
      variants precludes targeted healthcare. Here, we have modified a cell-free assay
      to test VUS in the MMR gene PMS2 for functional activity. We have analyzed nearly
      all VUS in PMS2 found thus far and describe loss of MMR activity for five,
      suggesting the applicability of the assay for diagnosis of LS. 

PMID- 24027008
TI  - Simultaneous determination of aurantio-obtusin, chrysoobtusin, obtusin and 1
      desmethylobtusin in rat plasma by UHPLC-MS/MS.
AB  - A sensitive and reliable ultra-high-performance liquid chromatography
      electrospray ionization-tandem mass spectrometry (UHPLC-MS/MS) method was
      developed and validated for the simultaneous determination of four active
      components of Semen Cassiae extract (aurantio-obtusin, chrysoobtusin, obtusin and
      1-desmethylobtusin) in rat plasma after oral administration. Chromatographic
      separation was achieved on an Agilent Poroshell 120 C18 column with gradient
      elution using a mobile phase that consisted of acetonitrile-ammonium acetate in
      water (30 mm) at a flow rate of 0.4 mL/min. Detection was performed by a triple
      quadrupole tandem mass spectrometer in multiple reaction monitoring mode. The
      calibration curve was linear over a range of 3.24-1296 ng/mL for aurantio
      obtusin, 0.77-618 ng/mL for chrysoobtusin, 34.55-1818 ng/mL for obtusin and 1.86
      1485 ng/mL for 1-desmethylobtusin. Inter- and intra-day assay variation was <15%.
      All analytes were shown to be stable during all sample storage and analysis
      procedures.

PMID- 24027011
TI  - Percutaneous transhepatic gallbladder drainage followed by elective laparoscopic
      cholecystectomy in patients with moderate acute cholecystitis under
      antithrombotic therapy.
AB  - BACKGROUND: Standard treatment for acute cholecystitis (AC) in patients receiving
      antithrombotic drugs has not been established. We evaluated the safety of
      percutaneous transhepatic gallbladder drainage (PTGBD) followed by elective
      laparoscopic cholecystectomy (LC) in patients with moderate AC who were receiving
      antithrombotics. METHODS: Seventy-five patients received PTGBD from January 2006
      to March 2013 followed by elective LC for moderate AC. Patients were divided into
      Group A, which consisted of patients receiving antithrombotic therapy (n = 23),
      and Group B, which included the remaining patients (n = 52). We analyzed clinical
      outcomes and perioperative complications between groups. RESULTS: No hemorrhagic
      events occurred during PTGBD insertion regardless of antithrombotic treatment.
      The open conversion rate was not significantly different between the two groups.
      Postoperative complications were found in 10 patients (13.3%). The rate of
      postoperative complications in Group A was slightly higher than that in Group B,
      but the difference was not significant (21.7% vs. 9.6%; P = 0.15). Complications
      associated with PTGBD occurred in six patients (8%). There were no significant
      differences in the incidence of these complications, operation time,
      intraoperative blood loss, or length of postoperative hospital stay. CONCLUSIONS:
      Percutaneous transhepatic gallbladder drainage followed by elective LC may be an
      effective therapeutic strategy for moderate AC in patients receiving
      antithrombotic therapy.

PMID- 24027012
TI  - Biodegradable salicylate-based poly(anhydride-ester) microspheres for controlled
      insulin delivery.
AB  - Salicylate-based poly(anhydride-esters) (PAEs) chemically incorporate salicylic
      acid (SA) into the polymer backbone, which is then delivered in a controlled
      manner upon polymer hydrolysis. In this work, a salicylate-based PAE is a carrier
      to encapsulate and deliver insulin. Polymer microspheres were formulated using a
      water/oil/water double-emulsion solvent evaporation technique. The microspheres
      obtained had a smooth surface, high protein encapsulation efficiency, and
      relatively low emulsifier content. Insulin was released in vitro for 15 days,
      with no signs of aggregation or unfolding of the secondary structure. The
      released insulin also retained bioactivity in vitro. Concurrently, SA was
      released from the microspheres with polymer degradation and anti-inflammatory
      activity was observed. Based upon these results, the formulated microspheres
      enable simultaneous delivery of insulin and SA, both retaining bioactivity
      following processing.

PMID- 24027013
TI  - Male internal reproductive structures of European pea crabs (Crustacea, Decapoda,
      Brachyura, Pinnotheridae): vas deferens morphology and spermatozoal
      ultrastructure.
AB  - Pea crabs of the subfamily Pinnotherinae (Pinnotheridae) have a high investment
      in reproduction and an outstanding reproductive output, probably as an adaptation
      to the required increase in reproductive rate due to the pinnotherids small size
      and their parasitic, host-dependant way of life. In the present study, we
      investigate the male internal reproductive structures and the ultrastructure of
      spermatozoa of Pinnotheres pisum and Nepinnotheres pinnotheres by histological
      methods and both scanning- and transmission electron microscopy. In the
      Brachyura, the male internal reproductive systems generally consist of paired
      testes and corresponding vasa deferentia where spermatozoa develop and mature.
      Spermatozoal ultrastructure of the investigated pinnotherids conforms to the
      thoracotreme type, however, N. pinnotheres has an accessory opercular ring and a
      periopercular rim, neither of which are present in spermatozoa of P. pisum.
      Spermatozoa are enclosed within spermatophores in the secretory proximal vas
      deferens. Two types of secretions were observed in P. pisum and N. pinnotheres:
      an electron dense substance secreted in the proximal vas deferens involved in
      spermatophore formation, and large electron-luscent vesicles constituting the
      seminal plasma in the medial and distal vas deferens. The medial vas deferens is
      strongly widened compared to other brachyurans to purpose storing spermatophores
      embedded in seminal plasma. Tubular appendices, which produce and store large
      amounts of seminal plasma, arise from the distal region of the vas deferens. The
      appendices extend into the ventral cephalothorax and also in the first pleomere.
      The latter being an exceptional location for reproductive structures among male
      brachyurans.

PMID- 24027015
TI  - The role of emotional control in the regulation of mood in parents of children
      with mucopolysaccharidosis.
AB  - The aim of our study was to evaluate whether, on the basis of variables related
      to emotional control, we can anticipate mood change in parents of chronically ill
      children. Fifty-four parents of children with diagnosed mucopolysaccharidosis
      participated in the study that was carried out during a rehabilitation programme
      for children with rare metabolic diseases. To assess emotional control, a Polish
      adaptation of the Courtauld Emotional Control Scale was used, and mood was
      measured with the UWIST Mood Adjective Checklist (UMACL). Mood was assessed
      twice, at an interval of 8 days, on the dimensions of hedonic tone, tense arousal
      and energetic arousal. The baseline level of each mood dimension accounted for
      about 30% of the mood variance measured after 8 days. After excluding the part of
      the mood variance associated with the baseline level, the variables related to
      emotional control appeared to be significant predictors of the mood assessed 8
      days later. For hedonic tone, variables related to emotional control explained
      15% of the variance; for tense arousal, it was 14% of the variance; and for
      energetic arousal, it was 10% of the variance. Depending on the type of emotion
      and the degree of control, differences in tendencies to respond with a particular
      mood were observed.

PMID- 24027014
TI  - Effectiveness of a theory-based intervention to increase colorectal cancer
      screening among Iranian health club members: a randomized trial.
AB  - Colorectal cancer is the third most commonly diagnosed cancer and the fourth
      leading cause of death in the world. There are few published studies that have
      used theory-based interventions designed to increase colorectal cancer screening
      in community lay health organizations. The present study was guided by the
      theoretical concepts of the preventive health model. Twelve health clubs of a
      municipal district in Tehran were randomized to two study groups with equal
      ratio. The control group received usual services throughout the study while the
      intervention group also received a theory-based educational program on colorectal
      cancer screening plus a reminder call. Screening behavior, the main outcome, was
      assessed 4 months after randomization. A total of 360 members aged 50 and older
      from 12 health clubs completed a baseline survey. Participants in the
      intervention group reported increased knowledge of colorectal cancer and
      screening tests at 4 months follow-up (p's < .001). Moreover, exposure to the
      theory-based intervention significantly improved self-efficacy, perceived
      susceptibility, efficacy of screening, social support, and intention to be
      screened for colorectal cancer, from baseline to 4 months follow-up (p's < .001).
      The screening rate for colorectal cancer was significantly higher in the
      intervention group compared to the control group (odds ratio = 15.93, 95% CI =
      5.57, 45.53). Our theory-based intervention was found to have a significant
      effect on colorectal cancer screening use as measured by self-report. The
      findings could have implications for colorectal cancer screening program
      development and implementation in primary health care settings and through other
      community organizations.

PMID- 24027016
TI  - Epstein-Barr virus (EBV) association and latency profile in pediatric Burkitt's
      lymphoma: experience of a single institution in Argentina.
AB  - The aim of this study is to characterize EBV expression and latency pattern in
      pediatric Burkitt's lymphoma in a single institution in Argentina. EBV-encoded
      RNA or protein was analyzed in 27 patients. EBERs was expressed in 37% of
      patients (29% of immunocompetent and 100% of immunosuppressed patients). EBV
      positive cases were observed exclusively in patients younger than 5 years old.
      EBV association with immunocompetent patients exhibits the sporadic pattern in
      region under study, while its presence in patients infected with HIV was higher
      than described previously. EBV latency I profile was present in most of the
      patients, except for two immunosuppressed patients who displayed LMP1 expression.

PMID- 24027017
TI  - Expulsion of micronuclei containing amplified genes contributes to a decrease in
      double minute chromosomes from malignant tumor cells.
AB  - Double minute chromosomes (DMs) are a hallmark of gene amplification. The
      relationship between the formation of DMs and the amplification of DM-carried
      genes remains to be clarified. The human colorectal cancer cell line NCI-H716 and
      human malignant primitive neuroectodermal tumor cell line SK-PN-DW are known to
      contain many DMs. To examine the amplification of DM-carried genes in tumor
      cells, we performed Affymetrix SNP Array 6.0 analyses and verified the regions of
      amplification in NCI-H716 and SK-PN-DW tumor cells. We identified the
      amplification regions and the DM-carried genes that were amplified and
      overexpressed in tumor cells. Using RNA interference, we downregulated seven DM
      carried genes, (NDUFB9, MTSS1, NSMCE2, TRIB1, FAM84B, MYC and FGFR2) individually
      and then investigated the formation of DMs, the amplification of the DM-carried
      genes, DNA damage and the physiological function of these genes. We found that
      suppressing the expression of DM-carried genes led to a decrease in the number of
      DMs and reduced the amplification of the DM-carried genes through the micronuclei
      expulsion of DMs from the tumor cells. We further detected an increase in the
      number of gammaH2AX foci in the knockdown cells, which provides a strong link
      between DNA damage and the loss of DMs. In addition, the loss of DMs and the
      reduced amplification and expression of the DM-carried genes resulted in a
      decrease in cell proliferation and invasion ability. 

PMID- 24027018
TI  - Regulation of MLH1 mRNA and protein expression by promoter methylation in primary
      colorectal cancer: a descriptive and prognostic cancer marker study.
AB  - BACKGROUND: In colorectal cancer MLH1 deficiency causes microsatellite
      instability, which is relevant for the patient's prognosis and treatment, and its
      putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter
      hypermethylation or by hereditary mutations as seen in Lynch Syndrome. The aim of
      this study was to determine in detail how DNA methylation regulates MLH1
      expression and impacts clinical management. METHODS: Colorectal cancer samples
      were collected from 210 patients. The laboratory methods used to study these
      samples included methylation specific multiplex ligation-dependent probe
      amplification (MS-MLPA), real-time quantitative PCR (qPCR), and
      immunohistochemistry (IHC). RESULTS: We found that the MLH1 mRNA and protein
      expression levels were highly related. MS-MLPA was successful in tumors from 195
      patients. In these tumors, hypermethylation was observed in promoter regions A (n
      = 57), B (n = 30), C (n = 28), and D (n = 47), and in intron 1 (n = 25). The
      promoter region C and intron 1 methylation levels were found to be excellently
      suited for discriminating between low and high gene expression levels, whereas
      those of promoter regions A, B and D were less specific. Hypermethylation in any
      region (n = 77) served as an independent prognostic factor (hazard ratio 0.56, 95
      % confidence interval 0.36-0.89, p = 0.01). CONCLUSIONS: MLH1 inactivation
      through hypermethylation was found to be related to improved survival.
      Hypermethylation in promoter region C and intron 1 served as the most specific
      markers for this inactivation.

PMID- 24027019
TI  - Suppression of growth and migration by blocking the Hedgehog signaling pathway in
      gastric cancer cells.
AB  - PURPOSE: Previous studies have indicated that Hedgehog signaling is essential for
      gastric cancer development, but its precise role is still unclear. The aim of
      this study was to clarify the role of Hedgehog signaling in gastric cancer
      development. METHODS: The expression of key Hedgehog signaling components in
      clinical samples of sequential gastric cancer stages was assessed by
      immunohistochemistry. The roles and regulatory mechanisms of Hedgehog signaling
      in human gastric cancer cells and normal gastric epithelial cells were
      investigated using multiple cell biological approaches and cDNA microarray
      analyses. RESULTS: Hedgehog signaling was found to be abnormally activated in a
      ligand-independent manner during gastric cancer development. Gli1 over-expression
      and reduced SuFu expression were found to be typical events in gastric cancer
      tissues. Gli1 over-expression was found to correlate with a poorly differentiated
      histology, advanced clinical stage, membrane serosa infiltration and lymph node
      metastasis in patients with gastric cancer. Data obtained from multiple cell
      biological assays showed that human gastric cancer cells require active Hedgehog
      signaling for survival, proliferation, migration and colony formation. N-Shh
      treatment significantly enhanced the migration, invasion and colony formation of
      gastric cancer cells. Moreover, the results of cDNA microarray analyses indicated
      that after treatment with cyclopamine or GANT61 (inhibitors of Hedgehog
      signaling), differentially expressed genes in gastric cancer cells were enriched
      in the apoptosis and MAPK pathways. Inhibitors of the Hedgehog pathway were found
      to suppress gastric cancer cell growth via apoptosis induction. CONCLUSIONS: Our
      findings indicate a vital role of the activated Hedgehog signaling pathway in
      promoting gastric initiation and progression. The Hedgehog signaling pathway may
      serve as a target for gastric cancer therapy.

PMID- 24027020
TI  - Toll-like receptor 2/6-dependent stimulation of mesenchymal stem cells promotes
      angiogenesis by paracrine factors.
AB  - Reconstruction of critical size bone defects represents a major challenge in
      orthopaedic surgery. Insufficient angiogenesis is a limiting factor for
      engraftment of large-scale tissue transplants. Transplantation or stimulation of
      local mesenchymal stem cells (MSCs) represents a potential solution to enhance
      angiogenesis. We recently identified angiogenic properties for the Toll-like
      receptor (TLR) 2/6 agonist MALP-2 and now investigated if MALP-2 could be used to
      stimulate MSCs in order to promote angiogenesis in vitro and in vivo. Human MSCs
      from the bone marrow of healthy subjects were isolated, cultured and expanded in
      vitro and were shown to be positive for mesenchymal stem cells markers as well as
      for the MALP-2 receptors TLR2 and TLR6. MALP-2 directly enhanced migration but
      not proliferation of human MSCs. Conditioned medium from MALP-2 stimulated MSCs
      significantly increased proliferation, migration and tube formation of
      endothelial cells. Analysis of the conditioned medium from MSCs revealed that
      MALP-2 stimulation enhanced the secretion of several chemokines and growth
      factors including vascular endothelial growth factors (VEGF) and granulocyte
      macrophage colony-stimulating factor (GM-CSF). Finally, we studied MALP-2 effects
      on MSCs in a sheep model of tissue engineering in vivo. Therefore, MSCs were
      isolated from the iliac crest of black head sheep and co-cultivated with MALP-2
      ex vivo. Implantation of autologous MSCs within a scaffold cylinder into the M.
      latissimus dorsi significantly enhanced vessel density of these constructs after
      6 months. We here present the first evidence that TLR2/6-dependent stimulation of
      MSCs promotes angiogenesis in vitro and in vivo offering a novel strategy for
      therapeutic angiogenesis, e.g., for tissue engineering of bone. 

PMID- 24027021
TI  - Inhibition of oncostatin M in osteoarthritic synovial fluid enhances GAG
      production in osteoarthritic cartilage repair.
AB  - Mediators in the synovial fluid are thought to play a major role in
      osteoarthritic cartilage turnover. The purpose of the current study was to
      investigate the role of oncostatin M (OSM) in osteoarthritis (OA) by evaluating
      the presence of the cytokine and its receptors in the OA joint and interfering
      with its activity in synovial fluid co-cultured with cartilage explants. OSM
      levels were increased in the synovial fluid of osteoarthritic patients compared
      to healthy donors. Immunohistochemistry confirmed the presence of both the
      leukaemia inhibitory factor (LIF) and OSM receptors for OSM throughout the whole
      depth of osteoarthritic cartilage and synovial tissue, whereas in healthy
      cartilage their presence seemed more restricted to the superficial zone. Blocking
      OSM activity, using an activity inhibiting antibody, in 25 % osteoarthritic
      synovial fluid added to OA cartilage explant cultures increased glycosaminoglycan
      (GAG) content from 18.6 mg/g to 24.3 mg/g (P < 0.03) and total production from
      7.0 mg/g to 11.9 mg/g (P < 0.003). However, OSM exogenously added to cartilage
      explant cultures reflecting low and high concentrations in the synovial fluid (5
      and 50 pg/mL) did not affect cartilage matrix turnover, suggesting that factors
      present in the synovial fluid act in concert with OSM to inhibit GAG production.
      The current study indicates the potential to enhance cartilage repair in
      osteoarthritis by modulating the joint environment by interfering with OSM
      activity. 

PMID- 24027022
TI  - A new take on an old story: chick limb organ culture for skeletal niche
      development and regenerative medicine evaluation.
AB  - Scientific research and progress, particularly in the drug discovery and
      regenerative medicine fields, is typically dependent on suitable animal models to
      develop new and improved clinical therapies for injuries and diseases. In vivo
      model systems are frequently utilised, but these models are expensive, highly
      complex and pose a number of ethical considerations leading to the development
      and use of a number of alternative ex vivo model systems. The ex vivo embryonic
      chick long bone and limb bud models have been utilised in the scientific research
      field as a model to understand skeletal development for over eighty years. The
      rapid development of avian skeletal tissues, coupled with the ease of
      experimental manipulation, availability of genome sequence and the presence of
      multiple cell and tissue types has seen such model systems gain significant
      research interest in the last few years in the tissue engineering field. The
      models have been explored both as systems for understanding the developmental
      bone niche and as potential testing tools for tissue engineering strategies for
      bone repair and regeneration. This review details the evolution of the chick limb
      organ culture system and presents recent innovative developments and emerging
      techniques and technologies applied to these models that are aiding our
      understanding of skeletal developmental and regenerative medicine research and
      application. 

PMID- 24027024
TI  - From dissecting cadavers to dissecting genomes.

PMID- 24027023
TI  - Best paper NASS 2013: link-N can stimulate proteoglycan synthesis in the
      degenerated human intervertebral discs.
AB  - Intervertebral disc (IVD) degeneration is the most common cause of back pain.
      Presently there is no medical treatment, leaving surgery as the only offered
      option. Here we evaluate the potential of Link-N to promote extracellular matrix
      regeneration in human IVDs. Human disc cells cultured in alginate and intact
      human discs were exposed to a combination of Link-N and 35SO4 in the presence or
      absence of interleukin (IL)-1, and the effect on proteoglycan synthesis was
      evaluated. In addition, message levels of aggrecan, matrix metalloproteinase
      (MMP)-3, MMP-13, a Disintegrin And Metalloproteinase with Thrombospondin Motifs
      (ADAMTS)-4 and ADAMTS-5 were evaluated in alginate cultures. Human disc cells
      responded in a dose dependent manner with maximal proteoglycan synthesis at 1
      ug/mL Link-N. Link-N treatment also induced proteoglycan synthesis in intact
      human discs, and a prolonged effect was found up to one week after Link-N
      treatment. Message levels of proteinases were decreased by Link-N in the presence
      of IL-1. Thus, Link-N can promote proteoglycan synthesis and deplete proteinase
      expression in adult human discs. Link-N could therefore be a promising candidate
      for biologically-induced disc repair, and could provide an alternative to
      surgical intervention for early stage disc degeneration.

PMID- 24027025
TI  - Vaccination with leishmania hemoglobin receptor-encoding DNA protects against
      visceral leishmaniasis.
AB  - Leishmaniasis is a severe infectious disease. Drugs used for leishmaniasis are
      very toxic, and no vaccine is available. We found that the hemoglobin receptor
      (HbR) of Leishmania was conserved across various strains of Leishmania, and anti
      HbR antibody could be detected in kala-azar patients' sera. Our results showed
      that immunization with HbR-DNA induces complete protection against virulent
      Leishmania donovani infection in both BALB/c mice and hamsters. Moreover, HbR-DNA
      immunization stimulated the production of protective cytokines like interferon
      gamma (IFN-gamma), interleukin-12 (IL-12), and tumor necrosis factor-alpha (TNF
      alpha) with concomitant down-regulation of disease-promoting cytokines like IL-10
      and IL-4. HbR-DNA vaccination also induced a protective response by generating
      multifunctional CD4(+) and CD8(+) T cells. All HbR-DNA-vaccinated hamsters showed
      sterile protection and survived during an experimental period of 8 months. These
      findings demonstrate the potential of HbR as a vaccine candidate against visceral
      leishmaniasis. 

PMID- 24027028
TI  - Effects of relevant and irrelevant color singletons on inhibition of return and
      attentional capture.
AB  - We tested whether color singletons lead to saccadic and manual inhibition of
      return (IOR; i.e., slower responses at cued locations) and whether IOR depended
      on the relevance of the color singletons. The target display was preceded by a
      nonpredictive cue display. In three experiments, half of the cues were response
      relevant, because participants had to perform a discrimination task at the cued
      location. With the exception of Experiment 2, none of the cue colors matched the
      target color. We observed saccadic IOR after color singletons, which was greater
      for slow than for fast responses. Furthermore, when the relevant cue color
      matched the target color, we observed attentional capture (i.e., faster responses
      at cued locations) with rapid responses, but IOR with slower responses, which
      provides evidence for attentional deallocation. When the cue display was
      completely response-irrelevant in two additional experiments, we did not find
      evidence for IOR. Instead, we found attentional capture when the cue color
      matched the target color. Also, attentional capture was greater for rapid
      responses and with short cue-target intervals. Thus, IOR emerges when cues are
      relevant and do not match the target color, whereas attentional capture emerges
      with relevant and irrelevant cues that match the target color. 

PMID- 24027027
TI  - Down-regulation of autophagy-related protein 5 (ATG5) contributes to the
      pathogenesis of early-stage cutaneous melanoma.
AB  - The role of autophagy in cancer is controversial: Both tumor-suppressing and
      tumor-promoting functions have been reported. We show that a key regulator of
      autophagy, autophagy-related protein 5 (ATG5), is often down-regulated in primary
      melanomas compared to benign nevi, leading to a reduction of basal autophagy as
      evidenced by a reduced expression of LC3. A follow-up of 158 primary melanoma
      patients showed that patients with low levels of ATG5 in their tumors had a
      reduced progression-free survival. In an in vitro model of melanoma
      tumorigenesis, where the BRAF oncogene was transduced into normal melanocytes, we
      observed that lowering ATG5 expression promoted proliferation by precluding
      oncogene-induced senescence. Hence, it appears that down-regulation of ATG5
      contributes to tumorigenesis in early-stage cutaneous melanoma, and the
      expression of ATG5 and LC3 correlates with melanoma diagnosis and prognosis. 

PMID- 24027026
TI  - A molecular signature predictive of indolent prostate cancer.
AB  - Many newly diagnosed prostate cancers present as low Gleason score tumors that
      require no treatment intervention. Distinguishing the many indolent tumors from
      the minority of lethal ones remains a major clinical challenge. We now show that
      low Gleason score prostate tumors can be distinguished as indolent and aggressive
      subgroups on the basis of their expression of genes associated with aging and
      senescence. Using gene set enrichment analysis, we identified a 19-gene signature
      enriched in indolent prostate tumors. We then further classified this signature
      with a decision tree learning model to identify three genes--FGFR1, PMP22, and
      CDKN1A--that together accurately predicted outcome of low Gleason score tumors.
      Validation of this three-gene panel on independent cohorts confirmed its
      independent prognostic value as well as its ability to improve prognosis with
      currently used clinical nomograms. Furthermore, protein expression of this three
      gene panel in biopsy samples distinguished Gleason 6 patients who failed
      surveillance over a 10-year period. We propose that this signature may be
      incorporated into prognostic assays for monitoring patients on active
      surveillance to facilitate appropriate courses of treatment.

PMID- 24027029
TI  - Motor IOR revealed for reaching.
AB  - Inhibition of return (IOR) is a spatial phenomenon that is thought to promote
      visual search functions by biasing attention and eye movements toward novel
      locations. Considerable research suggests distinct sensory and motor flavors of
      IOR, but it is not clear whether the motor type can affect responses other than
      eye movements. Most studies claiming to reveal motor IOR in the reaching control
      system have been confounded by their use of peripheral signals, which can invoke
      sensory rather than motor-based inhibitory effects. Other studies have used
      central signals to focus on motor, rather than sensory, effects in arm movements
      but have failed to observe IOR and have concluded that the motor form of IOR is
      restricted to the oculomotor system. Here, we show the first clear evidence that
      motor IOR can be observed for reaching movements when participants respond to
      consecutive central stimuli. This observation suggests that motor IOR serves a
      more general function than the facilitation of visual search, perhaps reducing
      the likelihood of engaging in repetitive behavior. 

PMID- 24027030
TI  - No time-stretching illusion when a tone is followed by a noise.
AB  - A sine tone is perceived as longer when it is preceded by a more intense noise
      than when presented in isolation. This is the time-stretching illusion. We
      conducted an experiment where the method of constant stimuli was used to examine
      whether a tone would also be stretched when it was followed by a noise. The
      duration of a tone was overestimated when it was preceded by a noise, but not
      when followed by a noise or when located between two consecutive noises.
      Moreover, the increasing of the noise intensity (from -6 to +6 dB) relative to
      the tone intensity resulted in larger overestimations, but only in the condition
      where a tone was preceded by a noise. In brief, the duration of a tone is
      stretched when this tone is preceded by a noise and if this tone is not followed
      by a noise.

PMID- 24027031
TI  - Armed and attentive: holding a weapon can bias attentional priorities in scene
      viewing.
AB  - The action-specific perception hypothesis (Witt, Current Directions in
      Psychological Science 20: 201-206, 2011) claims that the environment is
      represented with respect to potential interactions for objects present within
      said environment. This investigation sought to extend the hypothesis beyond
      perceptual mechanisms and assess whether action-specific potential could alter
      attentional allocation. To do so, we examined a well-replicated attention bias in
      the weapon focus effect (Loftus, Loftus, & Messo, Law and Human Behaviour 1, 55
      62, 1987), which represents the tendency for observers to attend more to weapons
      than to neutral objects. Our key manipulation altered the anticipated action
      specific potential of observers by providing them a firearm while they freely
      viewed scenes with and without weapons present. We replicated the original weapon
      focus effect using modern eye tracking and confirmed that the increase in time
      looking at weapons comes at a cost of less time spent looking at faces.
      Additionally, observers who held firearms while viewing the various scenes showed
      a general bias to look at faces over objects, but only if the firearm was in a
      readily usable position (i.e., pointed at the scenes rather than holstered at
      one's side). These two effects, weapon focus and the newly found bias to look
      more at faces when armed, canceled out one another without interacting. This
      evidence confirms that the action capabilities of the observer alter more than
      just perceptual mechanisms and that holding a weapon can change attentional
      priorities. Theoretical and real-world implications are discussed. 

PMID- 24027032
TI  - The relative influences of movement kinematics and extrinsic object
      characteristics on the perception of lifted weight.
AB  - Humans are able to perceive unique types of biological motion presented as point
      light displays (PLDs). Thirty years ago, Runeson and Frykholm (Human Perception
      and Performance, 7(4), 733, 1981, Journal of Experimental Psychology: General,
      112(4), 585, 1983) studied observers' perceptions of weights lifted by actors and
      identified that the kinematic information in a PLD is sufficient for an observer
      to form an accurate perception of the object weight. However, research has also
      shown that extrinsic object size characteristics also influence the perception of
      object weight (Gordon, Forssberg, Johansson, & Westling in Experimental Brain
      Research, 83(3), 477-482, 1991). This study addresses the relative contributions
      of these two types of visual information to observers' perceptions of lifted
      weight, through an experiment in which participants viewed an actor lifting boxes
      of various sizes (small, medium, or large) and weights (25, 50, or 75 lb) under
      four PLD conditions-box-at-rest, moving-box, actor-only, and actor-and-box-and
      one full-vision video condition, and then provided a weight estimate for each box
      lifted. The results indicated that lift kinematics and box size contributed
      independently to weight perception. Interestingly, the most robust weight
      differentiations were elicited in the conditions in which both types of
      information were presented concurrently, despite their converse natures.
      Furthermore, full-vision video presentation, which contained visual information
      beyond kinematics and object information, elicited the best estimates.

PMID- 24027033
TI  - The privileged role of location in visual working memory.
AB  - Reports have conflicted about the possible special role of location in visual
      working memory (WM). One important question is: Do we maintain the locations of
      objects in WM even when they are irrelevant to the task at hand? Here we used a
      continuous response scale to study the types of reporting errors that
      participants make when objects are presented at the same or at different
      locations in space. When several objects successively shared the same location,
      participants exhibited a higher tendency to report features of the wrong object
      in memory; that is, they responded with features that belonged to objects
      retained in memory but not probed at retrieval. On the other hand, a similar
      effect was not observed when objects shared a nonspatial feature, such as color.
      Furthermore, the effect of location on reporting errors was present even when its
      manipulation was orthogonal to the task at hand. These findings are consistent
      with the view that binding together different nonspatial features of an object in
      memory might be mediated through an object's location. Hence, spatial location
      may have a privileged role in WM. The relevance of these findings to conceptual
      models, as well as to neural accounts of visual WM, is discussed. 

PMID- 24027034
TI  - Modulation sensitivity in the perceptual organization of speech.
AB  - In a spoken utterance, a talker expresses linguistic constituents in serial
      order. A listener resolves these linguistic properties in the rapidly fading
      auditory sample. Classic measures agree that auditory integration occurs at a
      fine temporal grain. In contrast, recent studies have proposed that sensory
      integration of speech occurs at a coarser grain, approximate to the syllable, on
      the basis of indirect and relatively insensitive perceptual measures. Evidence
      from cognitive neuroscience and behavioral primatology has also been adduced to
      support the claim of sensory integration at the pace of syllables. In the present
      investigation, we used direct performance measures of integration, applying an
      acoustic technique to isolate the contribution of short-term acoustic properties
      to the assay of modulation sensitivity. In corroborating the classic finding of a
      fine temporal grain of integration, these functional measures can inform theory
      and speculation in accounts of speech perception. 

PMID- 24027035
TI  - Highly enantioselective Rh-catalysed hydrogenation of 1-alkyl vinyl esters using
      phosphine-phosphoramidite ligands.
AB  - MatPhos, a good mate for hard tasks: The asymmetric hydrogenation of 1-alkyl
      vinyl esters, thwarted so far by mediocre ee values and low activities, can now
      be achieved with MatPhos/Rh catalysts with ee values of 96-99% for a variety of
      substrates at low catalyst loadings (0.1-1 mol %) and under mild conditions (5-20
      bar H2, room temperature). After hydrolysis, the corresponding chiral secondary
      alkyl alcohols can be obtained in high enantiopurities providing a general and
      practical route to this important product class.

PMID- 24027036
TI  - Impact of genetic polymorphism on drug-drug interactions mediated by cytochromes:
      a general approach.
AB  - Currently, quantitative prediction of the impact of genetic polymorphism and drug
      drug interactions mediated by cytochromes, based on in vivo data, is made by two
      separate methods and restricted to a single cytochrome. We propose a unified
      approach for describing the combined impact of drug-drug interactions and genetic
      polymorphism on drug exposure. It relies on in vivo data and uses the following
      three characteristic parameters: one for the victim drug, one for the interacting
      drug, and another for the genotype. These parameters are known for a wide range
      of drugs and genotypes. The metrics of interest are the ratio of victim drug area
      under the curve (AUC) in patients with genetic variants taking both drugs, to the
      AUC in patients with either variant or wild-type genotype taking the victim drug
      alone. The approach was evaluated by external validation, comparing predicted and
      observed AUC ratios found in the literature. Data were found for 22 substrates,
      30 interacting drugs, and 38 substrate-interacting drug couples. The mean
      prediction error of AUC ratios was 0.02, and the mean prediction absolute error
      was 0.38 and 1.34, respectively. The model may be used to predict the variations
      in exposure resulting from a number of drug-drug-genotype combinations. The
      proposed approach will help (1) to identify comedications and population at risk,
      (2) to adapt dosing regimens, and (3) to prioritize the clinical pharmacokinetic
      studies to be done. 

PMID- 24027037
TI  - Evaluation of the alpha angle in asymptomatic adult hip joints: analysis of 994
      hips.
AB  - INTRODUCTION: Numerous studies on cam femoroacetabular impingement (FAI) causing
      osteoarthritis have been conducted in Western populations, but not in Asian
      populations. The alpha angle in cam type FAI can be measured by routine hip AP
      and axial radiographs. The purpose of this study was to determine the range of
      alpha angles in an asymptomatic Asian cohort. MATERIALS AND METHODS: We performed
      a retrospective examination on 500 asymptomatic Asian adults (1000 hips) who
      underwent simultaneous spine MRI and hip coronal survey MRI for evaluation of
      back pain from December 2009 to March 2010. The alpha angle was measured on
      anteroposterior (AP) pelvic survey images. According to inclusion criteria, 372
      hips of 186 men and 622 hips of 311 women were analysed. RESULTS: The mean alpha
      angles for men and women were 50.61 degrees  +/- 7.61 degrees  and 49.82 degrees 
      +/- 4.14 degrees , respectively with no statistically significant differences (p
      = 0.063). Alpha angles of the two age groups (>=50 years old and <50 years old)
      were similar in both genders: 49.90 degrees  +/- 6.88 degrees  versus 51.40
      degrees  +/- 8.30 degrees  in men (p = 0.060), and 50.61 degrees  +/- 7.61
      degrees  versus 49.82 degrees  +/- 4.14 degrees  in women (p = 0.71). The
      frequency of pathologic alpha angle of men and women was 0.5% and 3.1%,
      respectively. CONCLUSIONS: After review of 994 asymptomatic adult hips, we found
      neither gender-specific nor age-specific differences in the alpha angle. The
      frequency of the pathological range of the alpha angle was notably rare, as
      compared to those of Western countries. We assume that these findings could be
      related to a low prevalence of FAI and idiopathic osteoarthritis of the hip in
      the Asian population.

PMID- 24027038
TI  - Postoperative plasma D-dimer value for predicting deep venous thrombosis
      following hip arthroplasty with nadroparin prophylaxis.
AB  - The aim of the study was to assess the value of D-dimer as an event predicitor
      for deep vein thrombosis (DVT) in patients given low molecular weight heparin
      (LMWH) after total hip arthroplasty (THA). Plasma D-dimer levels were obtained
      preoperatively and at days 1, 3, and 7 postoperatively in 83 consecutive patients
      undergoing THA treated with nadroparin prophylaxis plus intermittent pneumatic
      compression. Unilateral ascending venography was performed at postoperative day 7
      or 8. There was a significant difference between the D-dimer levels in the DVT
      group (28 patients) and non-DVT group (55 patients) on each day (P<0.01). ROC
      analysis showed the AUC on postoperative days 1, 3 and 7 was 0.706, 0.712 and
      0.772 respectively. The D-dimer concentration on postoperative day 1, day 3 or
      day 7 is of moderate predicting value of DVT in patients undergoing THA, treated
      with nadroparin prophylaxis plus intermittent pneumatic compression. 

PMID- 24027039
TI  - Discovery and anatomy of the arenophilic system of cuspidariid clams (Bivalvia:
      Anomalodesmata).
AB  - The arenophilic system of anomalodesmatan clams comprises multicellular glands,
      muscular papillae, and radial lines of adhesive secretion, which glue sand grains
      and other extraneous particles to the external surface of the shell. The presence
      and morphology of these organs have been established in an increasing number of
      taxa, but arenophilic glands were not previously known to occur in the deep-sea,
      carnivorous family Cuspidariidae. Dissections, histological sections and
      ultrastructural examination of members of the cuspidariid genera Cuspidaria and
      Cardiomya revealed a functional arenophilic system positioned around the siphonal
      apparatus. Glands are contained in muscular papillae at the posterior tip of the
      siphonal sheath, from where they deposit their adhesive secretion onto the shell
      rostrum. Discovery of an arenophilic system in cuspidariid clams adds support to
      the idea that the glands are a synapomorphy of Anomalodesmata, secondarily absent
      in only one of the major component branches (the clade joining Thraciidae,
      Cleidothaeridae, and Myochamidae). Moreover, similarity between the arenophilic
      papillae we observed on the siphonal sheath of Cuspidaria, Cardiomya, and
      Myonera, and literature reports on the crown of tentacles of Multitentacula is
      puzzling and highlights the need for further studies of the latter genus.

PMID- 24027040
TI  - Clinical spectrum of LIG4 deficiency is broadened with severe dysmaturity,
      primordial dwarfism, and neurological abnormalities.
AB  - DNA double-strand break repair via non-homologous end joining (NHEJ) is involved
      in recombination of immunoglobulin and T-cell receptor genes. Mutations in NHEJ
      components result in syndromes that are characterized by microcephaly and
      immunodeficiency. We present a patient with lymphopenia, extreme
      radiosensitivity, severe dysmaturity, corpus callosum agenesis, polysyndactily,
      dysmorphic appearance, and erythema, which are suggestive of a new type of NHEJ
      deficiency. We identified two heterozygous mutations in LIG4. The p.S205LfsX29
      mutation results in lack of the nuclear localization signal and appears to be a
      null mutation. The second mutation p.K635RfsX10 lacks the C-terminal region
      responsible for XRCC4 binding and LIG4 stability and activity, and therefore this
      mutant might be a null mutation as well or have very low residual activity. This
      is remarkable since Lig4 knockout mice are embryonic lethal and so far in humans
      no complete LIG4 deficiencies have been described. This case broadens the
      clinical spectrum of LIG4 deficiencies. 

PMID- 24027041
TI  - Response to Relation between time of symptom onset of ST-segment elevation
      myocardial infarction and patient baseline characteristics: from the National
      Cardiovascular Data Registry.

PMID- 24027042
TI  - The redox-neutral approach to C-H functionalization.
AB  - The direct functionalization of C-H bonds is an attractive strategy in organic
      synthesis. Although several advances have been made in this area, the selective
      activation of inert sp(3) C-H bonds remains a daunting challenge. Recently, a new
      type of sp(3) C-H activation mode through internal hydride transfer has
      demonstrated the potential to activate remote sp(3) C-H linkages in an atom
      economic manner. This Minireview attempts to classify recent advances in this
      area including the transition to non-activated sp(3) C-H bonds and asymmetric
      hydride transfers.

PMID- 24027043
TI  - Testing potentiates new learning in the misinformation paradigm.
AB  - Retrieval enhanced suggestibility (RES) is the finding that the misinformation
      effect is exacerbated when a test precedes misleading postevent information
      (Chan, Thomas, & Bulevich Psychological Science 20: 66-73, 2009). In the present
      study, we tested three hypotheses relevant to RES. First, we examined whether
      retrieval of critical details was necessary for the RES effect. Second, we
      examined whether initial testing influenced the allocation of attention to
      critical details during postevent information processing. Finally, we examined
      whether RES resulted in impaired access to the originally learned information. We
      compared three groups of participants in three experiments: an identical-test
      group, a related-test group, and a standard misinformation group. Both testing
      groups were tested on the original event before the introduction of
      misinformation; however, the identical-test group took the same test before and
      after the misinformation, whereas the related-test group took different tests
      before and after misinformation. We found that testing before misleading
      postevent information affected attention allocation to details in the postevent
      narrative. Furthermore, the RES effect did not accompany reduced accessibility to
      the original information, as measured by a modified-modified free recall test.
      These data have implications for how testing may potentiate new learning. 

PMID- 24027045
TI  - Laparoscopic parenchyma-sparing pancreatectomy.
AB  - In recent years laparoscopic pancreatic procedures have developed rapidly, and
      reports of laparoscopic resection including laparoscopic distal pancreatectomy
      and laparoscopic pancreaticoduodenectomy have increased in number. On the other
      hand, many benign and low-grade malignant pancreatic lesions have recently been
      detected by the improved diagnostic modalities. Parenchyma-sparing pancreatectomy
      is a preferred surgical procedure for such benign and low-malignancy pancreatic
      lesions, because parenchyma-sparing pancreatectomy can avoid the unnecessary
      resection of the normal pancreatic parenchyma, thereby preserving the endocrine
      and exocrine functions of the pancreas. Simultaneously, laparoscopic surgery has
      contributed to minimally invasive approaches for various pancreatic surgical
      procedures. The combination of laparoscopic surgery and parenchyma-sparing
      pancreatectomy is an ideal surgical procedure for benign and low-grade malignant
      pancreatic lesions. For laparoscopic parenchyma-sparing pancreatectomy to become
      more widely known and its indications clarified, it is necessary to demonstrate
      the clinical benefits, technical feasibility, and safety of this complex and
      difficult surgical procedure. 

PMID- 24027046
TI  - Physiological and subjective responses after psychosocial stress in Chinese
      hepatitis B patients.
AB  - Compared with healthy participants, Chinese patients with hepatitis B (HB)
      experience more psychosocial stress. The present study provided the first
      examination of physiological and subjective responses to stress in Chinese HB
      patients. A standard psychosocial stressor, the Trier Social Stress Test (TSST),
      was administered to 26 Chinese HB patients and 24 healthy control participants.
      Cortisol concentrations were measured in blood samples collected before and after
      the stressor. Self-reported emotional responses and cardiovascular measures were
      examined before and after the TSST. Depression and anxiety were assessed using
      Hospital Anxiety and Depression Scale. Chinese HB patients exhibited higher
      cortisol response to the stressor than healthy control participants. Compared
      with healthy participants, Chinese HB patients showed higher levels of anxiety,
      depression and nervousness, and lower levels of calmness after the TSST. HB
      patients reported more negative life events in the previous 6 months and obtained
      higher adversity scores, as compared with control participants. Significant
      correlations were obtained between adversity scores and change cortisol secretion
      after TSST in HB patients, but not in healthy participants. This study firstly
      demonstrates that physiological and subjective responses to psychosocial stress
      among Chinese HB patients were different from that in healthy control
      participants.

PMID- 24027047
TI  - Liver-specific knockout of GRP94 in mice disrupts cell adhesion, activates liver
      progenitor cells, and accelerates liver tumorigenesis.
AB  - Liver cancer is one of the most common solid tumors, with poor prognosis and high
      mortality. Mutation or deletion of the tumor suppressor phosphatase and tensin
      homolog deleted on chromosome 10 (PTEN) is strongly correlated with human liver
      cancer. Glucose-regulated protein 94 (GRP94) is a major endoplasmic reticulum
      (ER) chaperone protein, but its in vivo function is still emerging. To study the
      role of GRP94 in maintaining liver homeostasis and tumor development, we created
      two liver-specific knockout mouse models with the deletion of Grp94 alone, or in
      combination with Pten, using the albumin-cre system. We demonstrated that while
      deletion of GRP94 in the liver led to hyperproliferation of liver progenitor
      cells, deletion of both GRP94 and PTEN accelerated development of liver tumors,
      including both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC),
      suggestive of progenitor cell origin. Furthermore, at the premalignant stage we
      observed disturbance of cell adhesion proteins and minor liver injury. When GRP94
      was deleted in PTEN-null livers, ERK was selectively activated. CONCLUSION: GRP94
      is a novel regulator of cell adhesion, liver homeostasis, and tumorigenesis.

PMID- 24027048
TI  - Loss of stromal JUNB does not affect tumor growth and angiogenesis.
AB  - The transcription factor AP-1 subunit JUNB has been shown to play a pivotal role
      in angiogenesis. It positively controls angiogenesis by regulating Vegfa as well
      as the transcriptional regulator Cbfb and its target Mmp13. In line with these
      findings, it has been demonstrated that tumor cell-derived JUNB promotes tumor
      growth and angiogenesis. In contrast to JUNB's function in tumor cells, the role
      of host-derived stromal JUNB has not been elucidated so far. Here, we show that
      ablation of Junb in stromal cells including endothelial cells (ECs), vascular
      smooth muscle cells (SMCs) and fibroblasts does not affect tumor growth in two
      different syngeneic mouse models, the B16-F1 melanoma and the Lewis lung
      carcinoma model. In-depth analyses of the tumors revealed that tumor angiogenesis
      remains unaffected as assessed by measurements of the microvascular density and
      relative blood volume in the tumor. Furthermore, we could show that the
      maturation status of the tumor vasculature, analyzed by the SMC marker
      expression, alpha-smooth muscle actin and Desmin, as well as the attachment of
      pericytes to the endothelium, is not changed upon ablation of Junb. Taken
      together, these results indicate that the pro-angiogenic functions of stromal
      JUNB are well compensated with regard to tumor angiogenesis and tumor growth. 

PMID- 24027050
TI  - Idiopathic generalised tremor syndrome in two cats.
AB  - Two male neutered domestic shorthair cats were evaluated for generalised tremors.
      On neurological examination both cats showed whole-body tremors, worsening with
      stress. A mainly cerebellar disorder was suspected. Blood examination,
      cerebrospinal fluid analysis and electrophysiological examination of both cats
      and magnetic resonance imaging of the brain in one cat were normal. Idiopathic
      generalised tremor syndrome (IGTS) was suspected owing to the exclusion of
      underlying causes and the clinical similarities with the syndrome in dogs.
      Treatment as recommended for dogs was initiated and resulted in improvement. This
      report describes the first cases of IGTS in cats. 

PMID- 24027049
TI  - MicroRNA expression profiles in Kaposi's sarcoma.
AB  - Kaposi's sarcoma (KS) is a mesenchymal tumor, caused by Human herpesvirus 8
      (HHV8) with molecular and cytogenetic changes poorly understood. To gain further
      insight on the underlying molecular changes in KS, we performed microRNA (miRNA)
      microarray analysis of 17 Kaposi's sarcoma specimens. Three normal skin specimens
      were used as controls. The most significant differentially expressed miRNA were
      confirmed by quantitative reverse transcriptase polymerase chain reaction (RT
      PCR). We detected in KS versus normal skin 185 differentially expressed miRNAs,
      76 were upregulated and 109 were downregulated. The most significantly
      downregulated miRNAs were miR-99a, miR-200 family, miR-199b-5p, miR-100 and miR
      335, whereas kshv-miR-K12-4-3p, kshv-miR-K12-1, kshv-miR-K12-2, kshv-miR-K12-4-5p
      and kshv-miR-K12-8 were significantly upregulated. High expression levels of kshv
      miR-K12-1 (p = 0.004) and kshv-miR-K12-4-3p (p = 0.001) was confirmed by RT-PCR.
      The predicted target genes for differentially expressed miRNAs included genes
      which are involved in a variety of cellular processes such as angiogenesis (i.e.
      THBS1) and apoptosis (i.e. CASP3, MCL1), suggesting a role for these miRNAs in
      Kaposi's sarcoma pathogenesis. 

PMID- 24027051
TI  - Effect of neutering and breed on femoral and tibial physeal closure times in male
      and female domestic cats.
AB  - The timing of physeal closure is dependent upon many factors, including gonadal
      steroids, and previous studies have shown that early neutering delays physeal
      closure. Pelvic and femoral radiographs of 808 cats were analysed and physes at
      the greater trochanter, proximal femur, distal femur and proximal tibia were
      recorded as being open or closed. Date of birth, gender, neuter status and breed
      of cases were recorded. Each physis was analysed individually at a specific age.
      The number of male entire (ME), male neutered (MN), female entire (FE), female
      neutered (FN), pedigree and non-pedigree cases at each of these ages was
      recorded. The number of cases that were open or closed at each stated age were
      compared between the neutered and entire, the female and male, and the pedigree
      and non-pedigree groups using a Fischer's exact test, with P <0.05 being
      considered significant. Seven hundred and eighty-three radiographs were included:
      359 MN, 95 ME, 237 FN and 92 FE. Ninety-six cats were pedigree and 687 were non
      pedigree. A statistically significant effect was shown with physes closing later
      in MN than in ME cats for the greater trochanter (P = 0.0037), distal femur (P =
      0.0205) and tibial tuberosity (P = 0.0003). No effect was shown for the proximal
      tibial or proximal femoral physes, nor for any physis when comparing FE with FN
      cats. No statistically significant effect of breed or sex was noted. Physeal
      closure will occur later in MN cats than in ME cats for the greater trochanteric,
      distal femoral and tibial tuberosity physes, and the potential clinical
      consequences of this should be evaluated further. 

PMID- 24027052
TI  - First report of Dracunculus insignis in two naturally infected cats from the
      northeastern USA.
AB  - Dracunculiasis is rarely reported in cats, yet over the last few years we have
      identified two cats with filarioid-like spirurid infections. Case 1 was a 9-year
      old cat with pituitary-dependent hyperadrenocorticism from New York tate from
      which four adult dracunculoid nematodes were isolated from its torso. Based on
      morphometric characteristics and parasite geographic distribution, the specimens
      were identified as Dracunculus insignis females; at least one of the females was
      gravid, suggestive of patent infection. Species identification was confirmed
      through amplification and sequence analysis of nuclear and mitochondrial loci.
      Case 2 was a 14-year-old diabetic cat from Massachusetts. Formalin-fixed sections
      were obtained from a subcutaneous mass excised from the left foreleg.
      Histopathological examination revealed a large nematode with morphometrical
      characteristics of Dracunculus, surrounded by lymphocytes and sheets of
      eosinophils. These two cases appear to be the first published reports of
      dracunculiasis in domestic cats in the USA, and based on the findings from case
      1, D insignis may be the species associated with both infections. 

PMID- 24027053
TI  - Prevalence of regional and distant metastasis in cats with advanced oral squamous
      cell carcinoma: 49 cases (2005-2011).
AB  - The objective of this study was to evaluate the prevalence of regional and
      distant metastasis in cats with advanced oral squamous cell carcinoma (SCC) in a
      retrospective case series. Forty-nine cats with cytologically- or
      histopathologically-confirmed oral SCC presented to the Matthew J Ryan Veterinary
      Hospital of the University of Pennsylvania. History, clinical and laboratory
      results, diagnostic imaging findings and survival times were obtained from the
      medical records of patients who received diagnostic evaluation for metastasis.
      The prevalence of metastasis was assessed by means of mandibular lymph node
      cytology and three-view thoracic radiography. The prevalence of mandibular lymph
      node metastasis was 31% (15/49). Evidence of possible thoracic metastasis was
      seen in 10% (5/49) of cases. Of the patients with mandibular lymph node
      metastasis, 53% (8/15) were maxillary, 27% mandibular (4/15), 13% sublingual
      (2/15) and 7% caudal pharyngeal (1/15). Pulmonary metastasis was seen in three
      mandibular, one maxillary and one sublingual mass. Forty-one patients died or
      were euthanased owing to progression of local disease, and seven patients were
      lost to follow-up. The prevalence of regional metastasis in this study was more
      common than most previously reported studies, while the rate of pulmonary
      metastasis was higher than has previously been published. Although significant
      conclusions cannot be drawn, control of the primary tumor, regardless of tumor
      size at diagnosis, appears to be an important factor in improving survival time,
      and therefore treatment of metastasis may be important in those cases where long
      term control of the primary tumor is possible. 

PMID- 24027054
TI  - Effect of single-cat versus multi-cat home history on perceived behavioral stress
      in domestic cats (Felis silvestrus catus) in an animal shelter.
AB  - This study investigates the effect of living with other cats in a prior home on
      stress levels of cats recently surrendered to an animal shelter. A total of 63
      cats was evaluated using a Cat-Stress-Score and an approach test. Cats were
      categorized in terms of previous home history with or without other cats. No
      significant difference was found in stress scores between cats from single-cat
      households and those from multiple-cat households, although single cats that had
      been in the shelter less than 4 days demonstrated higher stress levels. No
      significant difference was found between the two groups in terms of approach
      results. Results of this study suggest that, in traditional individual cage
      settings, cats that are not accustomed to living with other cats may experience
      more stress in the initial few days of attempting to adjust to shelter existence.
      Through the use of such assessments, shelter personnel may develop an increased
      awareness to the needs of these cats and attempt to provide measures to improve
      their well-being within the shelter environment. 

PMID- 24027055
TI  - Gender-related in vitro metabolism of hexaconazole and its enantiomers in rats.
AB  - In the present study we investigated the enantioselective disappearance of
      hexaconazole in rat liver microsomes system prepared from both genders. High
      performance liquid chromatography (HPLC) was used for identification and
      quantification. The degradation of the (+)-hexaconazole was faster than that of
      the (-)-hexaconazole in racemic hexaconazole and single enantiomer incubation in
      both sexes. The degradation half-life of the (+)-hexaconazole or (-)-hexaconazole
      was also gender-related. The metabolism of (+)-hexaconazole and (-)-hexaconazole
      were faster in male rat hepatic microsomes than that in female, suggesting that
      at least one of the cytochrome P450s (CYP) in the male rat liver microsomes
      system responsible for hexaconazole metabolism was male-specific or considerably
      more active. Kinetic assays showed that the intrinsic clearance in male rat liver
      microsomes was higher than that in female. All these results strongly suggest
      that sexual dimorphic metabolism of hexaconazole exists in rats. The inhibition
      experiments with CYP inhibitors showed that the inhibitory effect of inhibitors
      was enantioselective and affected by sex. The results suggest that the
      enantioselective metabolism of hexaconazole was determined by the amount of
      hepatic cytochrome P450 and the expression of individual isoforms of CYPs.

PMID- 24027056
TI  - A lipid storage-like disorder contributes to cognitive decline in HIV-infected
      subjects.
AB  - OBJECTIVE: In this multicenter cohort study, we sought to identify prognostic and
      associative metabolic indicators for HIV-associated neurocognitive disorders
      (HAND). METHODS: A quantitative lipidomic analysis was conducted on 524
      longitudinal CSF samples collected from 7 different performance sites across the
      mainland United States, Hawaii, and Puerto Rico. Subjects included HIV-infected
      individuals with longitudinal clinical and cognitive testing data and cognitively
      normal HIV-negative healthy controls. RESULTS: At baseline, HIV+ subjects could
      be differentiated from HIV- controls by reductions in a single ceramide species
      and increases in multiple forms of cholesterol. Perturbations in cholesterol
      metabolism and ceramide were influenced by combined antiretroviral therapy (cART)
      use. There were no cross-sectional baseline differences in any lipid metabolite
      when HIV+ subjects were grouped according to cognitive status. However, a single
      sphingolipid metabolite and reduced levels of esterified cholesterols were
      prognostic indicators of incident cognitive decline. Longitudinal patterns of
      these disturbances in sphingolipid and sterol metabolism suggest that a
      progressive disorder of lipid metabolism that is similar to disorders of lipid
      storage may contribute to the pathogenesis of HAND. CONCLUSIONS: These findings
      suggest that HIV infection and cART are independently associated with a CNS
      metabolic disturbance, identify surrogate markers that are prognostic for
      cognitive decline, and implicate a lipid storage-like disorder in the progression
      of HAND.

PMID- 24027058
TI  - Lipids and cognition make good bedfellows for neuroAIDS.

PMID- 24027059
TI  - Comment: double mutants of frontotemporal dementia genes--Simple co-occurrence?

PMID- 24027060
TI  - Episodic migraine and obesity and the influence of age, race, and sex.
AB  - OBJECTIVE: To evaluate the episodic migraine (EM)-obesity association and the
      influence of age, race, and sex on this relationship. METHODS: We examined the EM
      obesity association and the influence of age, race, and sex in 3,862 adult
      participants of both black and white race interviewed in the National Comorbidity
      Survey Replication. EM diagnostic criteria were based on the International
      Classification of Headache Disorders. Body mass index was classified as
      underweight (<18.5 kg/m(2)), normal (18.5-24.9 kg/m(2)), overweight (25-29.9
      kg/m(2)), or obese (>=30 kg/m(2)). Adjusted odds ratios (ORs) and 95% confidence
      intervals (CIs) for EM were estimated using logistic regression. Models were
      stratified by age (<50/>=50 years), race (white/black), and sex (male/female).
      RESULTS: A total of 188 participants fulfilled criteria for EM. In all
      participants, the adjusted odds of EM were 81% greater in individuals who were
      obese compared with those of normal weight (OR 1.81; 95% CI: 1.27-2.57; p =
      0.001), with a significant trend of increasing odds of EM with increasing obesity
      status from normal weight to overweight to obese (p = 0.001). In addition,
      stratified analyses demonstrated that the odds of EM were greater in obese as
      compared with normal-weight individuals who were 1) younger than 50 years of age
      (OR 1.86; 95% CI: 1.20-2.89; p for trend = 0.008), 2) white (OR 2.06; 95% CI:
      1.41-3.01; p for trend <=0.001), or 3) female (OR 1.95; 95% CI: 1.38-2.76; p for
      trend <=0.001). CONCLUSION: The odds of EM are increased in those with obesity,
      with the strongest relationships among those younger than 50 years, white
      individuals, and women.

PMID- 24027062
TI  - Reproductive morphology of three species of neotropical harvestmen (Opiliones,
      Laniatores, Gonyleptoidea).
AB  - Illustrations of penis morphology are essential components of species
      descriptions for harvestmen belonging to the suborder Laniatores. Male genitalia
      are important sources of taxonomic characters and are generally assumed to
      exhibit relatively little intraspecific variation. In contrast, descriptions of
      female reproductive morphology are rarely included in taxonomic descriptions of
      laniatorean harvestmen. As a result, relatively little is known about variation
      in the external features of the ovipositor. In this study, we used scanning
      electron microscopy to examine variation in male and female reproductive
      morphology among three species of harvestmen that are members of the superfamily
      Gonyleptoidea. Specifically, we examined the microanatomy of penises and
      ovipositors of Cynortula granulata (Cosmetidae), Phareicranaus calcariferus
      (Cranaidae), and Rhopalocranaus albilineatus (Manaosbiidae). Our results support
      the general observation that male reproductive morphology is conservative and
      displays little intraspecific variation. We observed considerable intraspecific
      variation in the number and shape of marginal setae on the ventral plate of the
      penis, but little or no variation in the morphology of the distal border of the
      ventral plate or the shape of the glans penis or stylus. With respect to female
      genitalia, we observed considerable intraspecific variation in the number of
      peripheral setae on the distal tip of the ovipositor. We also observed
      interspecific variation in the morphology of the peripheral setae (surface of the
      shaft and at shape of the distal tip), the distribution and morphology of smaller
      setae on the external surface of the ovipositor, and the surface texture of the
      external lobes. Our results indicate that there are several features associated
      with ovipositor morphology among laniatorean harvestmen that may represent
      potentially informative taxonomic characters.

PMID- 24027061
TI  - SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease.
AB  - OBJECTIVE: To investigate whether mutations in the SURF1 gene are a cause of
      Charcot-Marie-Tooth (CMT) disease. METHODS: We describe 2 patients from a
      consanguineous family with demyelinating autosomal recessive CMT disease (CMT4)
      associated with the homozygous splice site mutation c.107-2A>G in the SURF1 gene,
      encoding an assembly factor of the mitochondrial respiratory chain complex IV.
      This observation led us to hypothesize that mutations in SURF1 might be an
      unrecognized cause of CMT4, and we investigated SURF1 in a total of 40 unrelated
      patients with CMT4 after exclusion of mutations in known CMT4 genes. The
      functional impact of c.107-2A>G on splicing, amount of SURF1 protein, and on
      complex IV activity and assembly was analyzed. RESULTS: Another patient with CMT4
      was found to harbor 2 additional SURF1 mutations. All 3 patients with SURF1
      associated CMT4 presented with severe childhood-onset neuropathy, motor nerve
      conduction velocities <25 m/s, and lactic acidosis. Two patients had brain MRI
      abnormalities, including putaminal and periaqueductal lesions, and developed
      cerebellar ataxia years after polyneuropathy. The c.107-2A>G mutation produced no
      normally spliced transcript, leading to SURF1 absence. However, complex IV
      remained partially functional in muscle and fibroblasts. CONCLUSIONS: We found
      SURF1 mutations in 5% of families (2/41) presenting with CMT4. SURF1 should be
      systematically screened in patients with childhood-onset severe demyelinating
      neuropathy and additional features such as lactic acidosis, brain MRI
      abnormalities, and cerebellar ataxia developing years after polyneuropathy.

PMID- 24027057
TI  - C9ORF72 repeat expansions in cases with previously identified pathogenic
      mutations.
AB  - OBJECTIVE: To identify potential genetic modifiers contributing to the phenotypic
      variability that is detected in patients with repeat expansions in chromosome 9
      open reading frame 72 (C9ORF72), we investigated the frequency of these
      expansions in a cohort of 334 subjects previously found to carry mutations in
      genes known to be associated with a spectrum of neurodegenerative diseases.
      METHODS: A 2-step protocol, with a fluorescent PCR and a repeat-primed PCR, was
      used to determine the presence of hexanucleotide expansions in C9ORF72. For one
      double mutant, we performed Southern blots to assess expansion sizes, and
      immunohistochemistry to characterize neuropathology. RESULTS: We detected C9ORF72
      repeat expansions in 4 of 334 subjects (1.2% [or 1.8% of 217 families]). All
      these subjects had behavioral phenotypes and also harbored well-known pathogenic
      mutations in either progranulin (GRN: p.C466LfsX46, p.R493X, p.C31LfsX35) or
      microtubule-associated protein tau (MAPT: p.P301L). Southern blotting of one
      double mutant with a p.C466LfsX46 GRN mutation demonstrated a long repeat
      expansion in brain (>3,000 repeats), and immunohistochemistry showed mixed
      neuropathology with characteristics of both C9ORF72 expansions and GRN mutations.
      CONCLUSIONS: Our findings indicate that co-occurrence of 2 evidently pathogenic
      mutations could contribute to the pleiotropy that is detected in patients with
      C9ORF72 repeat expansions. These findings suggest that patients with known
      mutations should not be excluded from further studies, and that genetic
      counselors should be aware of this phenomenon when advising patients and their
      family members.

PMID- 24027064
TI  - WITHDRAWN: Chinese herbal medicine for atopic eczema.

PMID- 24027063
TI  - Two novel mutations in ABHD12: expansion of the mutation spectrum in PHARC and
      assessment of their functional effects.
AB  - PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataracts)
      is a recently described autosomal-recessive neurodegenerative disease caused by
      mutations in the alpha-beta-hydrolase domain-containing 12 gene (ABHD12). Only
      five homozygous ABHD12 mutations have been reported and the pathogenesis of PHARC
      remains unclear. We evaluated a woman who manifested short stature as well as the
      typical features of PHARC. Sequence analysis of ABHD12 revealed a novel
      heterozygous c.1129A>T (p.Lys377*) mutation. Targeted comparative genomic
      hybridization detected a 59-kb deletion that encompasses exon 1 of ABHD12 and
      exons 1-4 of an adjacent gene, GINS1, and includes the promoters of both genes.
      The heterozygous deletion was also carried by the patient's asymptomatic mother.
      Quantitative reverse transcription-PCR demonstrated ~50% decreased expression of
      ABHD12 RNA in lymphoblastoid cell lines from both individuals. Activity-based
      protein profiling of serine hydrolases revealed absence of ABHD12 hydrolase
      activity in the patient and 50% reduction in her mother. This is the first report
      of compound heterozygosity in PHARC and the first study to describe how a
      mutation might affect ABHD12 expression and function. The possible involvement of
      haploinsufficiency for GINS1, a DNA replication complex protein, in the short
      stature of the patient and her mother requires further studies. 

PMID- 24027066
TI  - Amino acids, peptides and proteins.

PMID- 24027065
TI  - Amikacin maturation model as a marker of renal maturation to predict glomerular
      filtration rate and vancomycin clearance in neonates.
AB  - BACKGROUND AND OBJECTIVE: Amikacin clearance has recently been proposed as a
      marker of renal maturation in neonates. However, the predictive value of this
      marker is still unknown. The objective of the present exploratory study was to
      evaluate the predictive performance of renal maturation model derived from
      amikacin to predict the glomerular filtration rate (GFR) and vancomycin clearance
      in neonates. METHODS: The GFR and vancomycin clearance in neonates were predicted
      using a maturation model derived from amikacin via estimation and simulation in a
      cohort of 116 neonates using non-linear mixed-effects modeling NONMEM(r)
      software. RESULTS: Our results demonstrate good correlations between predicted
      and observed GFR and vancomycin clearance in neonates. The square of the
      correlation coefficient, and means of the prediction error (2.5th-97.5th
      percentiles) and absolute prediction error (2.5th-97.5th percentiles) are 0.96,
      1.2 % (-39.7 to 30.0 %) and 12.3 % (0.4-39.7 %), respectively, for GFR, and 0.97,
      -11.3 % (-38.2 to 15.4 %) and 14.0 % (0.5-38.2 %), respectively, for vancomycin.
      The prediction error is not significantly correlated with age. CONCLUSION: An
      amikacin maturation model can precisely reflect maturation of glomerular
      filtration and thus predict the dosage regimens of other renally excreted drugs
      by glomerular filtration in neonates.

PMID- 24027072
TI  - Multifunctional nanoprobe for MRI/optical dual-modality imaging and radical
      scavenging.
AB  - The development of novel nanomaterials for the diagnosis and/or treatment of
      human diseases has become an important issue. In this work, a multifunctional
      theranostic agent was designed by covalently binding hydroxyl- and amino-bearing
      C60 derivatives (C60 O~10 (OH)~16 (NH2 )~6 (NO2 )~6 ?24 H2 O) with gadolinium
      diethylenetriaminepentaacetic acid (Gd-DTPA) to yield C60 O~10 (OH)~16 (NH2 )~6
      (NO2 )~6 ?24 H2 O/(Gd-DTPA)3 (DF1 Gd3 ). The obtained DF1 Gd3 shows more than
      fourfold contrast improvement over commercial Gd-DTPA along with multiwavelength
      fluorescent emission for dual-modality diagnosis. An inner-ear magnetic resonance
      imaging (MRI) study was designed as a model of biological barriers, including the
      blood/brain barrier (BBB) for DF1 Gd3 to investigate its in vivo behavior. This
      revealed that the fabricated contrast agent dramatically increases the local
      contrast but can not cross the middle ear/inner ear barrier and
      endolymph/perilymph barrier in the inner ear, and thus it is also BBB-prohibited
      in normal individuals. In vivo biodistribution studies suggested that 1) DF1 Gd3
      could circulate in vessels for a relatively long time and is mainly eliminated
      through liver and kidney, 2) DF1 Gd3 may potentially function as a liver-specific
      MRI contrast agent. Interestingly, DF1 Gd3 also shows an excellent quenching
      effect on hydroxyl radicals, as revealed by the DMPO spin trap/ESR method. The
      combination of enhanced MRI/FL imaging and local treatment of lesions is unique
      to DF1 Gd3 and potentiates the medical paradigm of "detect and treat/prevent" in
      combating human diseases related to reactive oxygen. 

PMID- 24027073
TI  - Authors' reply to the letter to the editor by Olivier J.M. Guilbaud.

PMID- 24027074
TI  - 25th anniversary article: galvanic replacement: a simple and versatile route to
      hollow nanostructures with tunable and well-controlled properties.
AB  - This article provides a progress report on the use of galvanic replacement for
      generating complex hollow nanostructures with tunable and well-controlled
      properties. We begin with a brief account of the mechanistic understanding of
      galvanic replacement, specifically focused on its ability to engineer the
      properties of metal nanostructures in terms of size, composition, structure,
      shape, and morphology. We then discuss a number of important concepts involved in
      galvanic replacement, including the facet selectivity involved in the dissolution
      and deposition of metals, the impacts of alloying and dealloying on the structure
      and morphology of the final products, and methods for promoting or preventing a
      galvanic replacement reaction. We also illustrate how the capability of galvanic
      replacement can be enhanced to fabricate nanomaterials with complex structures
      and/or compositions by coupling with other processes such as co-reduction and the
      Kirkendall effect. Finally, we highlight the use of such novel metal
      nanostructures fabricated via galvanic replacement for applications ranging from
      catalysis to plasmonics and biomedical research, and conclude with remarks on
      prospective future directions. 

PMID- 24027075
TI  - Lymph node dissection for intrahepatic cholangiocarcinoma: a critical review of
      the literature to date.
AB  - Definite policy or evidence in regards to the lymph node dissection (LND) for
      intrahepatic cholangiocarcinoma (ICC) does not exist at present. We review and
      summarize the current knowledge about LND for ICC in reference to the literature
      to date. A Pubmed search was done to find the relevant literature. Only English
      literature from 2000 to 2013 was retrieved, using key words "intrahepatic
      cholangiocarcinoma" and "lymph node". In all selected articles, those which
      included a description of the difference in the survival results between the
      presence of lymph node metastasis (LNM), execution rate of LND, or institutional
      policy for LND were included in this review. In all reviewed articles, survival
      results of the LNM-positive group, evaluated by the 5-year survival rate, median
      survival time, or recurrence-free survival time were clearly worse than the LNM
      negative group. However, the execution rate of LND was not often assessed, and
      therefore precise evaluation for the efficacy of LND is still controversial.
      Randomized controlled trials under the definite LND policy should be conducted to
      obtain precise survival results and clinical evaluation criteria for LND.

PMID- 24027076
TI  - Estimating and comparing time-dependent areas under receiver operating
      characteristic curves for censored event times with competing risks.
AB  - The area under the time-dependent ROC curve (AUC) may be used to quantify the
      ability of a marker to predict the onset of a clinical outcome in the future. For
      survival analysis with competing risks, two alternative definitions of the
      specificity may be proposed depending of the way to deal with subjects who
      undergo the competing events. In this work, we propose nonparametric inverse
      probability of censoring weighting estimators of the AUC corresponding to these
      two definitions, and we study their asymptotic properties. We derive confidence
      intervals and test statistics for the equality of the AUCs obtained with two
      markers measured on the same subjects. A simulation study is performed to
      investigate the finite sample behaviour of the test and the confidence intervals.
      The method is applied to the French cohort PAQUID to compare the abilities of two
      psychometric tests to predict dementia onset in the elderly accounting for death
      without dementia competing risk. The 'timeROC' R package is provided to make the
      methodology easily usable.

PMID- 24027077
TI  - New drug targets in metastatic melanoma.
AB  - Over the past 30 years, and despite extensive clinical research, the treatment
      options for metastatic melanoma have been limited. Single-agent and combination
      chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent
      therapy and combination regimes have failed to show significant improvement in
      overall survival. Recent advances and in-depth understanding of the biology of
      melanoma have contributed in the development of new agents and to a change in the
      consideration of melanoma as one of the most therapy-resistant malignancies.
      Since the discovery of activating mutations in the BRAF oncogene, there has been
      remarkable progress in the development of targeted therapies for unresectable and
      metastatic melanoma, with unprecedentedly high response rates. Inactivation of
      immune regulatory checkpoints that limit T cell responses to melanoma has
      provided clinically validated targets for cancer immunotherapy, resulting in
      durable tumour responses. The combination of both approaches may result in
      additional benefits. Here we discuss current molecular targeted treatment
      options, immunotherapy and promising ongoing research to develop new strategies
      to treat melanoma.

PMID- 24027078
TI  - Formation of a metal-organic framework with high surface area and gas uptake by
      breaking edges off truncated cuboctahedral cages.
AB  - Breaking edges off regular truncated cuboctahedra leads to a metal-organic
      framework (MOF) with polybenzene topology. This fully characterized MOF with
      lowest connectivity has the largest BET surface area among interpenetrated MOFs. 

PMID- 24027079
TI  - Youth hub-and-spoke model.

PMID- 24027081
TI  - Is alcohol consumption in Australia increasing or decreasing?

PMID- 24027080
TI  - Testosterone and homicidal behavior.

PMID- 24027082
TI  - The status quo as a good outcome: How the DSM-5 diagnostic criteria for
      generalized anxiety disorder remained unchanged from the DSM-IV criteria.

PMID- 24027083
TI  - Evaluation of rare variants in the new fanconi anemia gene ERCC4 (FANCQ) as
      familial breast/ovarian cancer susceptibility alleles.
AB  - Recently, it has been reported that biallelic mutations in the ERCC4 (FANCQ) gene
      cause Fanconi anemia (FA) subtype FA-Q. To investigate the possible role of ERCC4
      in breast and ovarian cancer susceptibility, as occurs with other FA genes, we
      screened the 11 coding exons and exon-intron boundaries of ERCC4 in 1573 index
      cases from high-risk Spanish familial breast and ovarian cancer pedigrees that
      had been tested negative for BRCA1 and BRCA2 mutations and 854 controls. The
      frequency of ERCC4 mutation carriers does not differ between cases and controls,
      suggesting that ERCC4 is not a cancer susceptibility gene. Interestingly, the
      prevalence of ERCC4 mutation carriers (one in 288) is similar to that reported
      for FANCA, whereas there are approximately 100-fold more FA-A than FA-Q patients,
      indicating that most biallelic combinations of ERCC4 mutations are embryo lethal.
      Finally, we identified additional bone-fide FA ERCC4 mutations specifically
      disrupting interstrand cross-link repair. 

PMID- 24027085
TI  - Liver transplantation for patients with human immunodeficiency virus and
      hepatitis C virus co-infection: update in 2013.
AB  - Because of the progress of anti-retroviral therapy (ART) for human
      immunodeficiency virus (HIV), mortality due to opportunistic infection resulting
      in AIDS has been remarkably reduced. However, meanwhile, half of those patients
      have died of end-stage liver cirrhosis due to hepatitis C virus (HCV) with liver
      cirrhosis and early occurrence of hepatocellular carcinoma. Recently, in 2013,
      non-cirrhotic portal hypertension due to ART drugs or still unknown mechanisms
      have become problematic with early progression of the disease in this patient
      population. Liver transplantation (LT) could be one treatment of choice in such
      cases, but the indications for LT perioperative management, including both HIV
      and HCV treatments and immunosuppression, are still challenging. In this review,
      we update the literature on HIV/HCV co-infection and LT as well as recent effort
      for modifying allocation system for those patients. 

PMID- 24027084
TI  - Perioperative nutrition interventions for women with ovarian cancer.
AB  - BACKGROUND: Women with ovarian cancer have been shown to be at significant risk
      of malnutrition with incidence rates described as being between 28% to 67%.
      Nutrition interventions may improve clinical outcomes positively, nutritional
      status or quality of life measures in this patient group. OBJECTIVES: This review
      was conducted to assess the effects of nutrition interventions during the
      perioperative period for women with ovarian cancer. SEARCH METHODS: Electronic
      searches were conducted of the Cochrane Gynaecological Cancer Group Specialised
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue
      7), Medline (1946 to July week 4 2012), Embase (1980 to 2012 week 31), DARE (to
      7th August 2012) AMED (1985 to April 2012), BNI (1992 to April 2012), CINAHL (to
      April 2012). We also searched trials databases, conference proceedings and
      related citation lists. Reference listings were handsearched. No restrictions
      were applied on language or date. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) in which women 18 years and over with any stage of ovarian cancer,
      including recurrent cancer, were in the perioperative phase of treatment and
      received any type of nutrition intervention. DATA COLLECTION AND ANALYSIS: Titles
      and abstracts were screened by two review authors with study selection discussed
      by a team. Pairs of review authors worked independently on data collection and
      compared findings. MAIN RESULTS: A total of 4092 titles were screened and 14 full
      text reports reviewed; a single small study met the inclusion criteria. In the
      included RCT, 40 women (35 with ovarian cancer) had extensive elective surgery
      including bowel resection for treatment of gynaecological malignancy.
      Randomisation was made to either early oral feeding (oral fluids in the first 24
      hours, solid foods on the following day) or to a 'traditional' feeding regimen
      where oral fluids and foods were delayed until there was evidence of bowel
      function. Most women in the early feeding group (14/18) were able to resume
      eating solid food one day after surgery. This resulted in a significantly shorter
      hospital stay with no increase in postoperative complications or change in
      quality of life measures in comparison with the women on the 'traditional'
      feeding regimen. The incidence of nausea and vomiting during the postoperative
      stay was similar in both groups and was noted in slightly more than half of the
      women. Overall survival was evaluated until 30 days following discharge from
      hospital; in this period, there was one death of a woman who had been in the
      'traditional oral feeding' group, cause of death was not noted. We assessed risk
      of bias and found no high risk of bias was identified in the methodology and
      reporting of the included study, although there was an increased risk of bias due
      to the small size of the study in which not all of the women had ovarian cancer.
      AUTHORS' CONCLUSIONS: Although women with ovarian cancer have been shown to be at
      risk of malnutrition, there is a lack of evidence derived from RCTs evaluating
      the identification, assessment and treatment of malnutrition during the
      perioperative phase of treatment. There is evidence from one small study that
      some women with ovarian cancer undergoing surgery with associated bowel resection
      may safely commence oral fluids within 24 hours of surgery and solid foods on the
      following day. Further research is required, including a RCT, to generate
      guidance concerning the treatment of malnutrition in this patient group.

PMID- 24027086
TI  - A review of cetacean lung morphology and mechanics.
AB  - Cetaceans possess diverse adaptations in respiratory structure and mechanics that
      are highly specialized for an array of surfacing and diving behaviors. Some of
      these adaptations and air management strategies are still not completely
      understood despite over a century of study. We have compiled the historical and
      contemporary knowledge of cetacean lung anatomy and mechanics in regards to
      normal lung function during ventilation and air management while diving. New
      techniques are emerging utilizing pulmonary mechanics to measure lung function in
      live cetaceans. Given the diversity of respiratory adaptations in cetaceans,
      interpretations of these results should consider species-specific anatomy,
      mechanics, and behavior.

PMID- 24027087
TI  - Fractionation of the human plasma proteome for monoclonal antibody proteomics
      based biomarker discovery 2: antigen identification by dot-blot array screening.
AB  - Immunization with complex mixtures, like the human plasma resulted in the
      generation of cloned mAb libraries (PlasmaScanTM and QuantiPlasmaTM libraries,
      with >1000 individual mAbs) reacting with a nonredundant set of antigenic
      epitopes. mAb proteomics refers to quasi-hypothesis-free profiling of plasma
      samples with nascent or cloned mAb libraries for the discovery of disease
      specific biomarkers. Once mAbs with biomarker potential have been identified, the
      next task is the determination of cognate antigens recognized by the respective
      mAbs. To determine the cognate protein antigen corresponding to each individual
      mAbs in the cloned mAb libraries, we have separated human plasma by consecutive
      steps of desalting and various chromatography procedures. The process resulted in
      783 fractions, which we termed "Analyte Library" (AL). The AL represents the
      human plasma proteome in relatively low-protein complexity fractions. Here, to
      determine the utility of the AL, we selected ten plasma proteins and checked for
      their presence in the fractions. Among the ten cases, the distribution of four
      selected plasma proteins matched expectations, as these proteins were present
      only in a few fractions corresponding to their physical, chemical, and
      biochemical properties. However, in six cases, we observed "smear" -like
      distribution or complete absence of the proteins, suggesting that protein-protein
      interactions or protein variants may alter the observed plasma distribution
      profiles. Nevertheless, we conclude that the AL is an efficient, high throughput
      tool to complement the mAb biomarker discovery process with cognate protein
      antigen identification for each mAbs. 

PMID- 24027088
TI  - "I knew from day one that i'm either gonna fight this thing or be defeated":
      African American parents' experiences of coping with breast cancer.
AB  - Few studies have explored how African American parents navigate breast cancer
      while parenting their school-age children. This focus-group study examined how
      African American parents cope with the diagnosis and treatment of breast cancer.
      Three focus groups were conducted with nine African American parents coping with
      breast cancer. Interviews were analyzed using content analysis. Participants
      described a variety of coping strategies. Five primary themes emerged:
      involvement in community of support, relationship with cancer, being the family
      emotional regulator, highlighting positives, and spirituality. Findings suggest
      that providers can improve the care of African American breast cancer patients
      and their families by facilitating patient advocacy, encouraging patients to
      reach out to various support systems, discussing with patients their children's
      functioning, and integrating spirituality into available support programs.
      Developing more culturally sensitive support groups that promote shared family
      understanding and open communication among African American parents and their
      children can facilitate better coping. 

PMID- 24027090
TI  - Mononuclear manganese-peroxo and bis(MU-oxo)dimanganese complexes bearing a
      common N-methylated macrocyclic ligand.
AB  - Mononuclear Mn(III) -peroxo and dinuclear bis(MU-oxo)Mn(III) 2 complexes that
      bear a common macrocyclic ligand were synthesized by controlling the
      concentration of the starting Mn(II) complex in the reaction of H2 O2 (i.e., a
      Mn(III) -peroxo complex at a low concentration (<=1 mM) and a bis(MU-oxo)Mn(III)
      2 complex at a high concentration (>=30 mM)). These intermediates were
      successfully characterized by various physicochemical methods such as UV-visible
      spectroscopy, ESI-MS, resonance Raman, and X-ray analysis. The structural and
      spectroscopic characterization combined with density functional theory (DFT)
      calculations demonstrated unambiguously that the peroxo ligand is bound in a side
      on fashion in the Mn(III) -peroxo complex and the Mn2 O2 diamond core is in the
      bis(MU-oxo)Mn(III) 2 complex. The reactivity of these intermediates was
      investigated in electrophilic and nucleophilic reactions, in which only the
      Mn(III) -peroxo complex showed a nucleophilic reactivity in the deformylation of
      aldehydes.

PMID- 24027091
TI  - Micellization of St/MMA gradient copolymers: a general picture of structural
      transitions in gradient copolymer micelles.
AB  - In this work, a gradient copolymer of styrene (St) and methyl methacrylate (MMA)
      is synthesized via reversible addition-fragmentation chain transfer living
      radical polymerization and its micellization behaviors in an acetone and water
      mixture are investigated by transmission electron microscopy, light scattering,
      and NMR spectroscopy. Three different kinds of transitions were found to coexist
      in a single system for the first time: a unimers to micelles transition, a star
      like micelles to crew-cut micelles transition resulting from the shrinkage of
      micelles, and morphological transitions from spherical micelles to cylindrical
      micelles to vesicles. Our findings provide a general picture of structural
      transitions and relaxation processes in gradient copolymer micelles, which can
      lead to the development of novel materials and applications based on gradient
      copolymers. 

PMID- 24027092
TI  - A direct evidence of morphological degradation on a nanometer scale in polymer
      solar cells.
AB  - In situ measurement of a polymer solar cell using micro grazing incidence small
      angle X-ray scattering (MUGISAXS) and current-voltage tracking is demonstrated.
      While measuring electric characteristics under illumination, morphological
      changes are probed by MUGISAXS. The X-ray beam (green) impinges on the photo
      active layer with a shallow angle and scatters on a 2d detector. Degradation is
      explained by the ongoing nanomorphological changes observed. 

PMID- 24027093
TI  - The current state of Bayesian methods in medical product development: survey
      results and recommendations from the DIA Bayesian Scientific Working Group.
AB  - Bayesian applications in medical product development have recently gained
      popularity. Despite many advances in Bayesian methodology and computations,
      increase in application across the various areas of medical product development
      has been modest. The DIA Bayesian Scientific Working Group (BSWG), which includes
      representatives from industry, regulatory agencies, and academia, has adopted the
      vision to ensure Bayesian methods are well understood, accepted more broadly, and
      appropriately utilized to improve decision making and enhance patient outcomes.
      As Bayesian applications in medical product development are wide ranging, several
      sub-teams were formed to focus on various topics such as patient safety, non
      inferiority, prior specification, comparative effectiveness, joint modeling,
      program-wide decision making, analytical tools, and education. The focus of this
      paper is on the recent effort of the BSWG Education sub-team to administer a
      Bayesian survey to statisticians across 17 organizations involved in medical
      product development. We summarize results of this survey, from which we provide
      recommendations on how to accelerate progress in Bayesian applications throughout
      medical product development. The survey results support findings from the
      literature and provide additional insight on regulatory acceptance of Bayesian
      methods and information on the need for a Bayesian infrastructure within an
      organization. The survey findings support the claim that only modest progress in
      areas of education and implementation has been made recently, despite substantial
      progress in Bayesian statistical research and software availability.

PMID- 24027089
TI  - The pain of tendinopathy: physiological or pathophysiological?
AB  - Tendon pain remains an enigma. Many clinical features are consistent with tissue
      disruption-the pain is localised, persistent and specifically associated with
      tendon loading, whereas others are not-investigations do not always match
      symptoms and painless tendons can be catastrophically degenerated. As such, the
      question 'what causes a tendon to be painful?' remains unanswered. Without a
      proper understanding of the mechanism behind tendon pain, it is no surprise that
      treatments are often ineffective. Tendon pain certainly serves to protect the
      area-this is a defining characteristic of pain-and there is often a plausible
      nociceptive contributor. However, the problem of tendon pain is that the relation
      between pain and evidence of tissue disruption is variable. The investigation
      into mechanisms for tendon pain should extend beyond local tissue changes and
      include peripheral and central mechanisms of nociception modulation. This review
      integrates recent discoveries in diverse fields such as histology, physiology and
      neuroscience with clinical insight to present a current state of the art in
      tendon pain. New hypotheses for this condition are proposed, which focus on the
      potential role of tenocytes, mechanosensitive and chemosensitive receptors, the
      role of ion channels in nociception and pain and central mechanisms associated
      with load and threat monitoring. 

PMID- 24027094
TI  - Modeling exposure-lag-response associations with distributed lag non-linear
      models.
AB  - In biomedical research, a health effect is frequently associated with protracted
      exposures of varying intensity sustained in the past. The main complexity of
      modeling and interpreting such phenomena lies in the additional temporal
      dimension needed to express the association, as the risk depends on both
      intensity and timing of past exposures. This type of dependency is defined here
      as exposure-lag-response association. In this contribution, I illustrate a
      general statistical framework for such associations, established through the
      extension of distributed lag non-linear models, originally developed in time
      series analysis. This modeling class is based on the definition of a cross-basis,
      obtained by the combination of two functions to flexibly model linear or
      nonlinear exposure-responses and the lag structure of the relationship,
      respectively. The methodology is illustrated with an example application to
      cohort data and validated through a simulation study. This modeling framework
      generalizes to various study designs and regression models, and can be applied to
      study the health effects of protracted exposures to environmental factors, drugs
      or carcinogenic agents, among others.

PMID- 24027096
TI  - Nitrile-nitrile C-C coupling at group 4 metallocenes to form 1-metalla-2,5-diaza
      cyclopenta-2,4-dienes: synthesis and reactivity.
AB  - The C?C coupling of aryl nitriles at Group 4 metallocenes leads to unusual ring
      strained 1-metalla-2,5-diaza-cyclopenta-2,4-dienes. The structural, energetic,
      and chemical properties of these complexes are described. The reactions of these
      compounds towards CH3 CN, H2 , CO2 , and HCl usually lead to the release of one
      nitrile and its replacement by different co-substrates. 

PMID- 24027095
TI  - High-throughput sequencing of T-cell receptors reveals a homogeneous repertoire
      of tumour-infiltrating lymphocytes in ovarian cancer.
AB  - The cellular adaptive immune system mounts a response to many solid tumours
      mediated by tumour-infiltrating T lymphocytes (TILs). Basic measurements of these
      TILs, including total count, show promise as prognostic markers for a variety of
      cancers, including ovarian and colorectal. In addition, recent therapeutic
      advances are thought to exploit this immune response to effectively fight
      melanoma, with promising studies showing efficacy in additional cancers. However,
      many of the basic properties of TILs are poorly understood, including
      specificity, clonality, and spatial heterogeneity of the T-cell response. We
      utilize deep sequencing of rearranged T-cell receptor beta (TCRB) genes to
      characterize the basic properties of TILs in ovarian carcinoma. Due to somatic
      rearrangement during T-cell development, the TCR beta chain sequence serves as a
      molecular tag for each T-cell clone. Using these sequence tags, we assess
      similarities and differences between infiltrating T cells in discretely sampled
      sections of large tumours and compare to T cells from peripheral blood. Within
      the limits of sensitivity of our assay, the TIL repertoires show strong
      similarity throughout each tumour and are distinct from the circulating T-cell
      repertoire. We conclude that the cellular adaptive immune response within ovarian
      carcinomas is spatially homogeneous and distinct from the T-cell compartment of
      peripheral blood.

PMID- 24027097
TI  - Interventions for protecting renal function in the perioperative period.
AB  - BACKGROUND: Various methods have been used to try to protect kidney function in
      patients undergoing surgery. These most often include pharmacological
      interventions such as dopamine and its analogues, diuretics, calcium channel
      blockers, angiotensin-converting enzyme (ACE) inhibitors, N-acetyl cysteine
      (NAC), atrial natriuretic peptide (ANP), sodium bicarbonate, antioxidants and
      erythropoietin (EPO). OBJECTIVES: This review is aimed at determining the
      effectiveness of various measures advocated to protect patients' kidneys during
      the perioperative period.We considered the following questions: (1) Are any
      specific measures known to protect kidney function during the perioperative
      period? (2) Of measures used to protect the kidneys during the perioperative
      period, does any one method appear to be more effective than the others? (3) Of
      measures used to protect the kidneys during the perioperative period,does any one
      method appear to be safer than the others? SEARCH METHODS: In this updated
      review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library, Issue 2, 2012), MEDLINE (Ovid SP) (1966 to August 2012)
      and EMBASE (Ovid SP) (1988 to August 2012). We originally handsearched six
      journals (Anesthesia and Analgesia, Anesthesiology, Annals of Surgery, British
      Journal of Anaesthesia, Journal of Thoracic and Cardiovascular Surgery, and
      Journal of Vascular Surgery) (1985 to 2004). However, because these journals are
      properly indexed in MEDLINE, we decided to rely on electronic searches only
      without handsearching the journals from 2004 onwards. SELECTION CRITERIA: We
      selected all randomized controlled trials in adults undergoing surgery for which
      a treatment measure was used for the purpose of providing renal protection during
      the perioperative period. DATA COLLECTION AND ANALYSIS: We selected 72 studies
      for inclusion in this review. Two review authors extracted data from all selected
      studies and entered them into RevMan 5.1; then the data were appropriately
      analysed. We performed subgroup analyses for type of intervention, type of
      surgical procedure and pre-existing renal dysfunction. We undertook sensitivity
      analyses for studies with high and moderately good methodological quality. MAIN
      RESULTS: The updated review included data from 72 studies, comprising a total of
      4378 participants. Of these, 2291 received some form of treatment and 2087 acted
      as controls. The interventions consisted most often of different pharmaceutical
      agents, such as dopamine and its analogues, diuretics, calcium channel blockers,
      ACE inhibitors, NAC, ANP, sodium bicarbonate, antioxidants and EPO or selected
      hydration fluids. Some clinical heterogeneity and varying risk of bias were noted
      amongst the studies, although we were able to meaningfully interpret the data.
      Results showed significant heterogeneity and indicated that most interventions
      provided no benefit.Data on perioperative mortality were reported in 41 studies
      and data on acute renal injury in 44 studies (all interventions combined).
      Because of considerable clinical heterogeneity (different clinical scenarios, as
      well as considerable methodological variability amongst the studies), we did not
      perform a meta-analysis on the combined data.Subgroup analysis of major
      interventions and surgical procedures showed no significant influence of
      interventions on reported mortality and acute renal injury. For the subgroup of
      participants who had pre-existing renal damage, the risk of mortality from 10
      trials (959 participants) was estimated as odds ratio (OR) 0.76, 95% confidence
      interval (CI) 0.38 to 1.52; the risk of acute renal injury (as reported in the
      trials) was estimated from 11 trials (979 participants) as OR 0.43, 95% CI 0.23
      to 0.80. Subgroup analysis of studies that were rated as having low risk of bias
      revealed that 19 studies reported mortality numbers (1604 participants); OR was
      1.01, 95% CI 0.54 to 1.90. Fifteen studies reported data on acute renal injury
      (criteria chosen by the individual studies; 1600 participants); OR was 1.03, 95%
      CI 0.54 to 1.97. AUTHORS' CONCLUSIONS: No reliable evidence from the available
      literature suggests that interventions during surgery can protect the kidneys
      from damage. However, the criteria used to diagnose acute renal damage varied in
      many of the older studies selected for inclusion in this review, many of which
      suffered from poor methodological quality such as insufficient participant
      numbers and poor definitions of end points such as acute renal failure and acute
      renal injury. Recent methods of detecting renal damage such as the use of
      specific biomarkers and better defined criteria for identifying renal damage
      (RIFLE (risk, injury, failure, loss of kidney function and end-stage renal
      failure) or AKI (acute kidney injury)) may have to be explored further to
      determine any possible benefit derived from interventions used to protect the
      kidneys during the perioperative period.

PMID- 24027098
TI  - Effects of six-membered carbohydrate rings on structure, stability, and kinetics
      of G-quadruplexes.
AB  - We have evaluated the conformational, thermal, and kinetic properties of
      d(TGGGGT) analogues with one or five of the ribose nucleotides replaced with the
      carbohydrate residues hexitol nucleic acid (HNA), cyclohexenyl nucleic acid
      (CeNA), or altritol nucleic acid (ANA). All of the modified oligonucleotides
      formed G-quadruplexes, but substitution with the six-membered rings resulted in a
      mixture of G-quadruplex structures. UV and CD melting analyses showed that the
      structure formed by d(TGGGGT) modified with HNA was stabilized whereas that
      modified with CeNA was destabilized, relative to the structure formed by the
      unmodified oligonucleotide. Substitution at the fourth base of the G-tract with
      ANA resulted in a greater stabilization effect than substitution at the first G
      residue; substitution with five ANA residues resulted in significant
      stabilization of the G-quadruplex. A single substitution with CeNA at the first
      base of the G-tract or five substitutions with HNA resulted in striking
      deceleration or acceleration of G-quadruplex formation, respectively. Our results
      shed light on the effect of the sugar moiety on the properties of G-quadruplex
      structures. 

PMID- 24027101
TI  - Human cortical and behavioral sensitivity to patterns of complex motion at
      eccentricity.
AB  - Complex patterns of image motion (contracting, expanding, rotating, and spiraling
      fields) are important in the coordination of visually guided behaviors. Whereas
      specialized detectors in monkey visual cortex show selectivity for particular
      patterns of complex motion, their representation in human visual cortex remains
      unclear. In the present study, functional magnetic resonance imaging (fMRI) was
      used to investigate the sensitivity of functionally defined regions of human
      visual cortex to parametrically modulated complex motion trajectories, coupled
      with complementary psychophysical testing. A unique stimulus design made it
      possible to disambiguate the neural responses and psychophysical sensitivity to
      complex motions per se from the distribution of local motions relative to the
      fovea, which are known to enhance cortical activity when presented radial to
      fixation. This involved presenting several small, separate motion fields in the
      periphery in a manner that distinguished them from global optic flow patterns.
      The patterns were morphed through complex motion space in a systematic time
      locked fashion when presented in the scanner. Anisotropies were observed in the
      fMRI signal, marked by an enhanced response to expanding vs. contracting fields,
      even in early visual cortex. Anisotropies in the psychophysical sensitivity
      measures followed a similar pattern that was correlated with activity in areas
      hV4, V5/MT, and MST. This represents the first systematic examination of complex
      motion perception at both a behavioral and neural level in human observers. The
      characteristic processing anisotropy revealed in both data sets can inform models
      of complex motion processing, particularly with respect to computations performed
      in early visual cortex.

PMID- 24027100
TI  - Recall of spatial patterns stored in a hippocampal slice by long-term
      potentiation.
AB  - Nervous systems are thought to encode information as patterns of electrical
      activity distributed sparsely through networks of neurons. These networks then
      process information by transforming one pattern of electrical activity into
      another. To store information as a pattern, a neural network must strengthen
      synapses between designated neurons so that activation of some of these neurons
      corresponding to some features of an object can spread to activate the larger
      group representing the complete object. This operation of pattern completion
      endows a neural network with autoassociative memory. Pattern completion by neural
      networks has been modeled extensively with computers and invoked in behavioral
      studies, but experiments have yet to demonstrate pattern completion in an intact
      neural circuit. In the present study, imaging with voltage-sensitive dye in the
      CA3 region of a hippocampal slice revealed different spatial patterns of activity
      elicited by electrical stimulation of different sites. Stimulation of two
      separate sites individually, or both sites simultaneously, evoked "partial" or
      "complete" patterns, respectively. A complete pattern was then stored by applying
      theta burst stimulation to both sites simultaneously to induce long-term
      potentiation (LTP) of synapses between CA3 pyramidal cells. Subsequent
      stimulation of only one site then activated an extended pattern. Quantitative
      comparisons between response maps showed that the post-LTP single-site patterns
      more closely resembled the complete dual-site pattern. Thus, LTP induction
      enabled the CA3 region to complete a dual-site pattern upon stimulation of only
      one site. This experiment demonstrated that LTP induction can store information
      in the CA3 region of the hippocampus for subsequent retrieval.

PMID- 24027099
TI  - Impact of inhibitory constraint of interneurons on neuronal excitability.
AB  - Tonic inhibition is thought to dampen the excitability of principal neurons;
      however, little is known about the role of tonic GABAergic inhibition in
      interneurons and the impact on principal neuron excitability. In many brain
      regions, tonic GABAergic inhibition is mediated by extrasynaptic, delta-subunit
      containing GABAA receptors (GABAARs). In the present study we demonstrate the
      importance of GABAAR delta-subunit-mediated tonic inhibition in interneurons.
      Selective elimination of the GABAAR delta-subunit from interneurons was achieved
      by crossing a novel floxed Gabrd mouse model with GAD65-Cre mice (Gabrd/Gad
      mice). Deficits in GABAAR delta-subunit expression in GAD65-positive neurons
      result in a decrease in tonic GABAergic inhibition and increased excitability of
      both molecular layer (ML) and stratum radiatum (SR) interneurons. Disinhibition
      of interneurons results in robust alterations in the neuronal excitability of
      principal neurons and decreased seizure susceptibility. Gabrd/Gad mice have
      enhanced tonic and phasic GABAergic inhibition in both CA1 pyramidal neurons and
      dentate gyrus granule cells (DGGCs). Consistent with alterations in hippocampal
      excitability, CA1 pyramidal neurons and DGGCs from Gabrd/Gad mice exhibit a shift
      in the input-output relationship toward decreased excitability compared with
      those from Cre(-/-) littermates. Furthermore, seizure susceptibility, in response
      to 20 mg/kg kainic acid, is significantly decreased in Gabrd/Gad mice compared
      with Cre(-/-) controls. These data demonstrate a critical role for GABAAR delta
      subunit-mediated tonic GABAergic inhibition of interneurons on principal neuronal
      excitability and seizure susceptibility.

PMID- 24027102
TI  - Nonnociceptive afferent activity depresses nocifensive behavior and nociceptive
      synapses via an endocannabinoid-dependent mechanism.
AB  - Previously, low-frequency stimulation (LFS) of a nonnociceptive touch-sensitive
      neuron has been found to elicit endocannabinoid-dependent long-term depression
      (eCB-LTD) in nociceptive synapses in the leech central nervous system (CNS) that
      requires activation of a presynaptic transient receptor potential vanilloid
      (TRPV)-like receptor by postsynaptically synthesized 2-arachidonoyl glycerol (2
      AG). This capacity of nonnociceptive afferent activity to reduce nociceptive
      signaling resembles gate control of pain, albeit longer lasting in these synaptic
      experiments. Since eCB-LTD has been observed at a single sensory-motor synapse,
      this study examines the functional relevance of this mechanism, specifically
      whether this form of synaptic plasticity has similar effects at the behavioral
      level in which additional, intersegmental neural circuits are engaged.
      Experiments were carried out using a semi-intact preparation that permitted both
      synaptic recordings and monitoring of the leech whole body shortening, a
      defensive withdrawal reflex that was elicited via intracellular stimulation of a
      single nociceptive neuron (the N cell). The same LFS of a nonnociceptive afferent
      that induced eCB-LTD in single synapses also produced an attenuation of the
      shortening reflex. Similar attenuation of behavior was also observed when 2-AG
      was applied. LFS-induced behavioral and synaptic depression was blocked by
      tetrahydrolipstatin (THL), a diacylglycerol lipase inhibitor, and by SB366791, a
      TRPV1 antagonist. The effects of both THL and SB366791 were observed following
      either bath application of the drug or intracellular injection into the
      presynaptic (SB366791) or postsynaptic (THL) neuron. These findings demonstrate a
      novel, endocannabinoid-based mechanism by which nonnociceptive afferent activity
      may modulate nocifensive behaviors via action on primary afferent synapses.

PMID- 24027105
TI  - Influences of premotoneuronal command statistics on the scaling of motor output
      variability during isometric plantar flexion.
AB  - This study focuses on neuromuscular mechanisms behind ankle torque and EMG
      variability during a maintained isometric plantar flexion contraction.
      Experimentally obtained torque standard deviation (SD) and soleus, medial
      gastrocnemius, and lateral gastrocnemius EMG envelope mean and SD increased with
      mean torque for a wide range of torque levels. Computer simulations were
      performed on a biophysically-based neuromuscular model of the triceps surae
      consisting of premotoneuronal spike trains (the global input, GI) driving the
      motoneuron pools of the soleus, medial gastrocnemius, and lateral gastrocnemius
      muscles, which activate their respective muscle units. Two types of point
      processes were adopted to represent the statistics of the GI: Poisson and Gamma.
      Simulations showed a better agreement with experimental results when the GI was
      modeled by Gamma point processes having lower orders (higher variability) for
      higher target torques. At the same time, the simulations reproduced well the
      experimental data of EMG envelope mean and SD as a function of mean plantar
      flexion torque, for the three muscles. These results suggest that the
      experimentally found relations between torque-EMG variability as a function of
      mean plantar flexion torque level depend not only on the intrinsic properties of
      the motoneuron pools and the muscle units innervated, but also on the increasing
      variability of the premotoneuronal GI spike trains when their mean rates increase
      to command a higher plantar flexion torque level. The simulations also provided
      information on spike train statistics of several hundred motoneurons that compose
      the triceps surae, providing a wide picture of the associated mechanisms behind
      torque and EMG variability.

PMID- 24027103
TI  - Optical imaging of cortical networks via intracortical microstimulation.
AB  - Understanding cortical organization is key to understanding brain function.
      Distinct neural networks underlie the functional organization of the cerebral
      cortex; however, little is known about how different nodes in the cortical
      network interact during perceptual processing and motor behavior. To study
      cortical network function we examined whether the optical imaging of intrinsic
      signals (OIS) reveals the functional patterns of activity evoked by electrical
      cortical microstimulation. We examined the effects of current amplitude, train
      duration, and depth of cortical stimulation on the hemodynamic response to
      electrical microstimulation (250-Hz train, 0.4-ms pulse duration) in anesthetized
      New World monkey somatosensory cortex. Electrical stimulation elicited a
      restricted cortical response that varied according to stimulation parameters and
      electrode depth. Higher currents of stimulation recruited more areas of cortex
      than smaller currents. The largest cortical responses were seen when stimulation
      was delivered around cortical layer 4. Distinct local patches of activation,
      highly suggestive of local projections, around the site of stimulation were
      observed at different depths of stimulation. Thus we find that specific
      electrical stimulation parameters can elicit activation of single cortical
      columns and their associated columnar networks, reminiscent of anatomically
      labeled networks. This novel functional tract tracing method will open new
      avenues for investigating relationships of local cortical organization.

PMID- 24027106
TI  - Purinergic modulation of norepinephrine release and uptake in rat brain cortex:
      contribution of glial cells.
AB  - The pathogenesis of psychiatric and neurodegenerative diseases is often
      associated with a deregulation of noradrenergic transmission. Considering the
      potential involvement of purinergic signaling in the modulation of noradrenergic
      transmission in the brain cortex, this study aimed to identify the P2Y receptor
      subtypes involved in the modulation of neuronal release and neuronal/glial uptake
      of norepinephrine. Electrical stimulation (100 pulses at 5 Hz) of rat cortical
      slices induced norepinephrine release that was inhibited by ATP and ADP (0.01-1
      mM), adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS, 0.03-0.3 mM), and UDP (0.1-1
      mM). The effect of ADPbetaS was mediated by P2Y1 receptors and possibly by
      A1/P2Y1 heterodimers since it was attenuated by the A1 receptor antagonist DPCPX
      and by the P2Y1 receptor antagonist MRS 2500 but was resistant to the effect of
      adenosine deaminase (ADA). UDP inhibited norepinephrine release through
      activation of P2Y6 receptors, an effect that was abolished by the P2Y6 receptor
      antagonist MRS 2578 and by DPCPX, indicating that it depends on the formation
      and/or release of adenosine and activation of A1 receptors. Supporting this
      hypothesis, the inhibitory effect of UDP was also prevented by inhibition of
      ectonucleotidases, by ADA and was attenuated by the inhibitor of nucleoside
      transporter 6-[(4-nitrobenzyl)thio]-9-beta-d-ribofuranosylpurine (NBTI).
      Additionally, the inhibitory effect of UDP was attenuated when norepinephrine
      uptake 1 or 2 was inhibited. In astroglial cultures, ADPbetaS and UDP increased
      norepinephrine uptake mainly by activation of P2Y1 and P2Y6 receptors,
      respectively. The results indicate that neuronal and glial P2Y1 and P2Y6
      receptors may represent new targets of intervention to regulate noradrenergic
      transmission in CNS diseases.

PMID- 24027104
TI  - Neurophysiological correlates of aging-related muscle weakness.
AB  - Muscle weakness associated with aging implicates central neural degeneration.
      However, role of the primary motor cortex (M1) is poorly understood, despite
      evidence that gains in strength in younger adults are associated with its
      adaptations. We investigated whether weakness of biceps brachii in aging
      analogously relates to processes in M1. We enrolled 20 young (22.6 +/- 0.87 yr)
      and 28 old (74.79 +/- 1.37 yr) right-handed participants. Using transcranial
      magnetic stimulation, representation of biceps in M1 was identified. We examined
      the effect of age and sex on strength of left elbow flexion, voluntary activation
      of biceps, corticospinal excitability and output, and short-interval
      intracortical and interhemispheric inhibition. Interhemispheric inhibition was
      significantly exaggerated in the old (P = 0.047), while strength tended to be
      lower (P = 0.075). Overall, women were weaker (P < 0.001). Processes of M1
      related to strength or voluntary activation of biceps, but only in older adults.
      Corticospinal excitability was lower in weaker individuals (r = 0.38), and
      corticospinal output, intracortical inhibition and interhemispheric inhibition
      were reduced too in individuals who poorly activated biceps (r = 0.43, 0.54 and
      0.38). Lower intracortical inhibition may reflect compensation for reduced
      corticospinal excitability, allowing weaker older adults to spread activity in M1
      to recruit synergists and attempt to sustain motor output. Exaggerated
      interhemispheric inhibition, however, conflicts with previous evidence,
      potentially related to greater callosal damage in our older sample, our choice of
      proximal vs. distal muscle and differing influence of measurement of inhibition
      in rest vs. active states of muscle. Overall, age-specific relation of M1 to
      strength and muscle activation emphasizes that its adaptations only emerge when
      necessitated, as in a weakening neuromuscular system in aging.

PMID- 24027108
TI  - A flexible and highly pressure-sensitive graphene-polyurethane sponge based on
      fractured microstructure design.
AB  - A fractured microstructure design: A new type of piezoresistive sensor with ultra
      high-pressure sensitivity (0.26 kPa(-1) ) in low pressure range (<2 kPa) and
      minimum detectable pressure of 9 Pa has been fabricated using a fractured
      microstructure design in a graphene-nanosheet-wrapped polyurethane (PU) sponge.
      This low-cost and easily scalable graphene-wrapped PU sponge pressure sensor has
      potential application in high-spatial-resolution, artificial skin without complex
      nanostructure design. 

PMID- 24027107
TI  - Synaptic and extrasynaptic transmission of kidney-related neurons in the rostral
      ventrolateral medulla.
AB  - The rostral ventrolateral medulla (RVLM) is a critical component of the
      sympathetic nervous system regulating homeostatic functions including arterial
      blood pressure. Using the transsynaptic retrograde viral tracer PRV-152, we
      identified kidney-related neurons in the RVLM. We found that PRV-152-labeled RVLM
      neurons displayed an unusually large persistent, tonic current to both glutamate,
      via N-methyl-d-aspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4
      yl)propanoic acid (AMPA)/kainate receptors, and to gamma-aminobutyric acid
      (GABA), via GABAA receptors, in the absence of large-scale phasic
      neurotransmission with whole cell patch-clamp recordings. A cocktail of potent
      NMDA and AMPA/kainate ionotropic glutamate receptor antagonists AP-5 (50 MUM) and
      CNQX (10 MUM) revealed a two-component somatic tonic excitatory current with an
      overall amplitude of 42.6 +/- 13.4 pA. Moreover, application of the GABAA
      receptor blockers gabazine (15 MUM) and bicuculline (30 MUM) revealed a robust
      somatic tonic inhibitory current with an average amplitude of 196.3 +/- 39.3 pA.
      These findings suggest that the tonic current plays a role in determining the
      resting membrane potential, input resistance, and firing rate of RVLM neurons.
      The magnitude of the tonic inhibitory current demonstrates that GABAergic
      inhibition plays a critical role in regulation of kidney-related RVLM neurons.
      Our results indicate that the GABAergic tonic current may determine the basal
      tone of firing activity in kidney-related RVLM neurons.

PMID- 24027109
TI  - Laparoscopic surgery is applicable for larger mucinous cystic neoplasms of the
      pancreas.
AB  - BACKGROUND: Mucinous cystic neoplasms (MCN) of the pancreas frequently develop in
      the distal pancreases of young women. Laparoscopic surgery can enhance cosmetic
      benefits and ease of surgery. This study assessed the feasibility of laparoscopic
      surgery for MCN. METHODS: The medical records of 21 patients pathologically
      diagnosed with benign MCN after laparoscopic resection were reviewed. Clinical
      data were compared in the 11 patients with tumors >= 45 mm (large tumor group)
      and the 10 patients with tumors < 45 mm (small tumor group). RESULTS:
      Laparoscopic resection was completed in all patients, including distal
      pancreatectomy with (n = 9) and without (n = 11) spleen preservation and
      enucleation for pancreatic head lesion (n = 1). Operation time, blood loss,
      postoperative morbidity, and hospital stay were similar in the two groups. Spleen
      preserving pancreatectomy could be more frequently completed in the small MCN
      group (P = 0.02). No recurrence was observed during a median follow-up period of
      12 months. CONCLUSIONS: Laparoscopic surgery can be completed in all patients
      with benign MCN, even those with large tumors, and patients with small MCN can
      get the additional benefit of spleen preservation.

PMID- 24027111
TI  - The use of pharmacometrics to optimize biosimilar development.
AB  - Pharmacometric approaches can assist in biosimilar development by leveraging
      quantitative knowledge of the originator product characteristics such as dose
      exposure and exposure-response information to support a targeted approach to
      clinical studies. The degree to which these approaches can be applied relies on
      the level of information known about the originator and information that supports
      application of the originator model to the biosimilar. A model-based approach
      testing the hypothesis that the biosimilar PK and/or PK/PD profile is similar to
      the originator in the target patient population is aligned with the central
      comparability exercise required for the biosimilar approval. This Commentary
      details the key opportunities in study design and study analysis where
      pharmacometrics approaches can aid biosimilar development.

PMID- 24027110
TI  - TigarB causes mitochondrial dysfunction and neuronal loss in PINK1 deficiency.
AB  - OBJECTIVE: Loss of function mutations in PINK1 typically lead to early onset
      Parkinson disease (PD). Zebrafish (Danio rerio) are emerging as a powerful new
      vertebrate model to study neurodegenerative diseases. We used a pink1 mutant
      (pink(-/-) ) zebrafish line with a premature stop mutation (Y431*) in the PINK1
      kinase domain to identify molecular mechanisms leading to mitochondrial
      dysfunction and loss of dopaminergic neurons in PINK1 deficiency. METHODS: The
      effect of PINK1 deficiency on the number of dopaminergic neurons, mitochondrial
      function, and morphology was assessed in both zebrafish embryos and adults.
      Genome-wide gene expression studies were undertaken to identify novel pathogenic
      mechanisms. Functional experiments were carried out to further investigate the
      effect of PINK1 deficiency on early neurodevelopmental mechanisms and microglial
      activation. RESULTS: PINK1 deficiency results in loss of dopaminergic neurons as
      well as early impairment of mitochondrial function and morphology in Danio rerio.
      Expression of TigarB, the zebrafish orthologue of the human, TP53-induced
      glycolysis and apoptosis regulator TIGAR, was markedly increased in pink(-/-)
      larvae. Antisense-mediated inactivation of TigarB gave rise to complete
      normalization of mitochondrial function, with resulting rescue of dopaminergic
      neurons in pink(-/-) larvae. There was also marked microglial activation in pink(
      /-) larvae, but depletion of microglia failed to rescue the dopaminergic neuron
      loss, arguing against microglial activation being a key factor in the
      pathogenesis. INTERPRETATION: Pink1(-/-) zebrafish are the first vertebrate model
      of PINK1 deficiency with loss of dopaminergic neurons. Our study also identifies
      TIGAR as a promising novel target for disease-modifying therapy in PINK1-related
      PD.

PMID- 24027112
TI  - Effect of microneedle geometry and supporting substrate on microneedle array
      penetration into skin.
AB  - Microneedles are being fast recognized as a useful alternative to injections in
      delivering drugs, vaccines, and cosmetics transdermally. Owing to skin's inherent
      elastic properties, microneedles require an optimal geometry for skin
      penetration. In vitro studies, using rat skin to characterize microneedle
      penetration in vivo, require substrates with suitable mechanical properties to
      mimic human skin's subcutaneous tissues. We tested the effect of these two
      parameters on microneedle penetration. Geometry in terms of center-to-center
      spacing of needles was investigated for its effect on skin penetration, when
      placed on substrates of different hardness. Both hard (clay) and soft
      (polydimethylsiloxane, PDMS) substrates underneath rat skin and full-thickness
      pig skin were used as animal models and human skins were used as references. It
      was observed that there was an increase in percentage penetration with an
      increase in needle spacing. Microneedle penetration with PDMS as a support under
      stretched rat skin correlated better with that on full-thickness human skin,
      while penetration observed was higher when clay was used as a substrate. We
      showed optimal geometries for efficient penetration together with recommendation
      for a substrate that could better mimic the mechanical properties of human
      subcutaneous tissues, when using microneedles fabricated from poly(ethylene
      glycol)-based materials.

PMID- 24027113
TI  - The relationship between neutrophil-to-lymphocyte ratio and coronary collateral
      circulation.
AB  - Neutrophil/lymphocyte ratio (NLR) has been proposed as a prognostic marker to
      determine systemic inflammatory response and atherosclerosis. Our aim was to
      determine the relationship between NLR and development of coronary collateral
      circulation (CCC) in patients with stable coronary artery disease (CAD). A total
      of 521 consecutive patients with stable CAD who underwent coronary angiography
      and documented total occlusion in one of those major coronary arteries were
      included in this study. Levels of fasting blood glucose, white blood cell, and
      NLR were significantly higher in patients with poor collateral than in those with
      good collateral. After multivariate analysis, high level of NLR was an
      independent predictor of CCC together with levels of fasting blood glucose. The
      receiver-operating characteristic analysis provided a cutoff value of 2.75 for
      NLR to predict poor CCC with 65% sensitivity and 68% specificity. We demonstrated
      an independent association between levels of NLR and development of CCC in
      patients with stable CAD. 

PMID- 24027114
TI  - High-performance sensors based on molybdenum disulfide thin films.
AB  - High-performance sensors based on molybdenum disulfide (MoS2 ) grown by
      sulfurization of sputtered molybdenum layers are presented. Using a simple
      integration scheme, it is found that the electrical conductivity of MoS2 films is
      highly sensitive to NH3 adsorption, consistent with n-type semiconducting
      behavior. A sensitivity of 300 ppb at room temperature is achieved, showing the
      high potential of 2D transition metal-dichalcogenides for sensing. 

PMID- 24027115
TI  - Size controlled synthesis of silicon nanocrystals using cationic surfactant
      templates.
AB  - Alkyl-terminated silicon nanocrystals (Si NCs) are synthesized at room
      temperature by hydride reduction of silicon tetrachloride (SiCl4) within inverse
      micelles. Highly monodisperse Si nanocrystals with average diameters ranging from
      2 to 6 nm are produced by variation of the cationic quaternary ammonium salts
      used to form the inverse micelles. Transmission electron microscopy imaging shows
      that the NCs are highly crystalline, while FTIR spectra confirm that the NCs are
      passivated by covalent attachment of alkanes, with minimal surface oxidation. UV
      vis absorbance and photoluminescence spectroscopy show significant quantum
      confinement effects, with moderate absorption in the UV spectral range, and a
      strong blue emission with a marked dependency on excitation wavelength. The
      photoluminescence quantum yield (Phi) of the Si NCs exhibits an inverse
      relationship with the mean NC diameter, with a maximum of 12% recorded for 2 nm
      NCs.

PMID- 24027116
TI  - Cerebral arteriovenous malformation: complex 3D hemodynamics and 3D blood flow
      alterations during staged embolization.
AB  - Complex hemodynamics in cerebral arteriovenous malformations (AVM) are thought to
      play a key role in their pathophysiology. We applied 4D flow magnetic resonance
      imaging (MRI) for the detailed evaluation of AVM function at baseline and to
      investigate the impact of staged embolization on AVM hemodynamics in a patient
      with a Spetzler-Martin grade III AVM. The patient underwent three embolization
      procedures resulting in >50% nidal casting and obliteration of several
      arteriovenous fistulae. 4D flow MRI demonstrated highly complex 3D hemodynamics
      at baseline and revealed intricate arterial feeding, a large vascularized nidus
      with high variability in regional blood flow velocities, and clearly visible
      venous drainage with high flow velocities above 50 cm/s. 3D blood flow
      visualization and quantification during follow-up illustrated the systemic impact
      of focal embolization on cerebral hemodynamics resulting in compaction of the
      AVM, redistribution of blood flow velocities, and altered peak flow velocities
      and blood flow in multiple vascular territories. 4D flow MRI may offer a useful
      noninvasive tool to help to identify subtleties and nuances of the quantitative
      hemodynamic alterations in AVM vascular architecture as a supplement to
      established imaging modalities.

PMID- 24027117
TI  - The inhibition of oleic acid induced hepatic lipogenesis and the promotion of
      lipolysis by caffeic acid via up-regulation of AMP-activated kinase.
AB  - BACKGROUND: Caffeic acid (CA) can inhibit toxin-induced liver injury. In this
      study, CA is assessed for its lipid lowering potential when oleic acid is used to
      induce non-alcoholic fatty liver disease in human HepG2 cells. RESULTS: The
      results showed that both the triglyceride and cholesterol content are decreased
      in the HepG2 cells by using the enzymatic colorimetric method. CA enhances the
      phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream
      targeting enzyme, acetyl-CoA carboxylase. CA down-regulates the lipogenesis gene
      expression of sterol regulatory element-binding protein-1 and its target genes,
      fatty acid synthase in the presence of oleic acid. In addition, CA significantly
      decreases cholesterol and triglyceride production via inhibition the expression
      of both 3-hydroxy-3-methyglutary coenzyme A reductase and glycerol-3-phosphate
      acyltransferase. These effects are eliminated by pretreatment with compound C, an
      AMPK inhibitor. CONCLUSIONS: These results demonstrate that CA inhibits oleic
      acid induced hepatic lipogenesis and the promotion of lipolysis via up-regulation
      of AMP-activated kinase.

PMID- 24027118
TI  - Beta blockers for peripheral arterial disease.
AB  - BACKGROUND: Beta (beta) blockers are indicated for use in coronary artery disease
      (CAD). However, optimal therapy for people with CAD accompanied by intermittent
      claudication has been controversial because of the presumed peripheral
      haemodynamic consequences of beta blockers, leading to worsening symptoms of
      intermittent claudication. This is an update of a review first published in 2008.
      OBJECTIVES: To quantify the potential harmful effects of beta blockers on maximum
      walking distance, claudication distance, calf blood flow, calf vascular
      resistance and skin temperature when used in patients with peripheral arterial
      disease (PAD). SEARCH METHODS: For this update, the Cochrane Peripheral Vascular
      Diseases Group Trials Search Co-ordinator searched the Specialised Register (last
      searched March 2013) and the Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, 2013, Issue 2). SELECTION CRITERIA: Randomised
      controlled trials (RCTs) evaluating the role of both selective (beta1) and non
      selective (beta1 and beta2) beta blockers compared with placebo. We excluded
      trials that compared different types of beta blockers. DATA COLLECTION AND
      ANALYSIS: Primary outcome measures were claudication distance in metres, time to
      claudication in minutes and maximum walking distance in metres and minutes (as
      assessed by treadmill).Secondary outcome measures included calf blood flow
      (mL/100 mL/min), calf vascular resistance and skin temperature (oC). MAIN
      RESULTS: We included six RCTs that fulfilled the above criteria, with a total of
      119 participants. The beta blockers studied were atenolol, propranolol, pindolol
      and metoprolol. All trials were of poor quality with the drugs administered over
      a short time (10 days to two months). None of the primary outcomes were reported
      by more than one study. Similarly, secondary outcome measures, with the exception
      of vascular resistance (as reported by three studies), were reported, each by
      only one study. Pooling of such results was deemed inappropriate. None of the
      trials showed a statistically significant worsening effect of beta blockers on
      time to claudication, claudication distance and maximal walking distance as
      measured on a treadmill, nor on calf blood flow, calf vascular resistance and
      skin temperature, when compared with placebo. No reports described adverse events
      associated with the beta blockers studied. AUTHORS' CONCLUSIONS: Currently, no
      evidence suggests that beta blockers adversely affect walking distance, calf
      blood flow, calf vascular resistance and skin temperature in people with
      intermittent claudication. However, because of the lack of large published
      trials, beta blockers should be used with caution, if clinically indicated.

PMID- 24027120
TI  - Nonparametric modeling and analysis of association between Huntington's disease
      onset and CAG repeats.
AB  - Huntington's disease (HD) is a neurodegenerative disorder with a dominant genetic
      mode of inheritance caused by an expansion of CAG repeats on chromosome 4.
      Typically, a longer sequence of CAG repeat length is associated with increased
      risk of experiencing earlier onset of HD. Previous studies of the association
      between HD onset age and CAG length have favored a logistic model, where the CAG
      repeat length enters the mean and variance components of the logistic model in a
      complex exponential-linear form. To relax the parametric assumption of the
      exponential-linear association to the true HD onset distribution, we propose to
      leave both mean and variance functions of the CAG repeat length unspecified and
      perform semiparametric estimation in this context through a local kernel and
      backfitting procedure. Motivated by including family history of HD information
      available in the family members of participants in the Cooperative Huntington's
      Observational Research Trial (COHORT), we develop the methodology in the context
      of mixture data, where some subjects have a positive probability of being risk
      free. We also allow censoring on the age at onset of disease and accommodate
      covariates other than the CAG length. We study the theoretical properties of the
      proposed estimator and derive its asymptotic distribution. Finally, we apply the
      proposed methods to the COHORT data to estimate the HD onset distribution using a
      group of study participants and the disease family history information available
      on their family members.

PMID- 24027121
TI  - Synthesis and morphology control of AM-6 nanofibers with tailored -V-O-V-
      intermediates.
AB  - Microporous vanadosilicates with octahedral VO6 and tetrahedral SiO4 units,
      better known as AM-6, have been hydrothermally synthesized with different
      morphologies by controlling the Na/K molar ratio of the initial gel mixtures. The
      morphology of the AM-6 materials changed from bulky cube to nanofiber aggregates
      as the Na/K molar ratio decreased from 1.9 to 0.2. Raman spectroscopy revealed
      that the VO3 (-) intermediate species plays an important role in the formation of
      the nanofiber morphology. The orientation of -V-O-V- chains in nanofiber
      aggregates was examined by confocal polarized micro-Raman spectroscopy. It was
      found that these aggregates are assemblies of short -V-O-V- chains perpendicular
      to the axis of nanofibers. The obtained AM-6 nanofibers greatly increase the
      exposed proportion of V?O terminals, and thus improve the catalytic performance. 

PMID- 24027119
TI  - Sex-specific control of central nervous system autoimmunity by p38 mitogen
      activated protein kinase signaling in myeloid cells.
AB  - OBJECTIVE: Multiple sclerosis (MS) is a chronic inflammatory demyelinating
      disease of the central nervous system (CNS), characterized by a global increasing
      incidence driven by relapsing-remitting disease in females. Investigators have
      described p38 mitogen-activated protein kinase (MAPK) as a key regulator of
      inflammatory responses in autoimmunity, but its role in the sexual dimorphism in
      MS or MS models remains unexplored. METHODS: Toward this end, we used
      experimental autoimmune encephalomyelitis (EAE), the principal animal model of
      MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and
      transcriptomic analyses. RESULTS: Pharmacologic inhibition of p38 MAPK
      selectively ameliorated EAE in female mice. Conditional deletion studies
      demonstrated that p38alpha signaling in macrophages/myeloid cells, but not T
      cells or dendritic cells, mediated this sexual dimorphism, which was dependent on
      the presence of adult sex hormones. Analysis of CNS inflammatory infiltrates
      showed that female but not male mice lacking p38alpha in myeloid cells exhibited
      reduced immune cell activation compared with controls, whereas peripheral T-cell
      priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells
      revealed differences in p38alpha-controlled transcripts comprising female- and
      male-specific gene modules, with greater p38alpha dependence of proinflammatory
      gene expression in females. INTERPRETATION: Our findings demonstrate a key role
      for p38alpha in myeloid cells in CNS autoimmunity and uncover important molecular
      mechanisms underlying sex differences in disease pathogenesis. Taken together,
      our results suggest that the p38 MAPK signaling pathway represents a novel target
      for much needed disease-modifying therapies for MS.

PMID- 24027123
TI  - Magnetically engineered microcapsules as intracellular anchors for remote control
      over cellular mobility.
AB  - Living cells are anchored with magnetic microcapsules that allow in vitro
      manipulation via a magnetic field. 

PMID- 24027122
TI  - Neural bases of individual variation in decision time.
AB  - People make decisions by evaluating existing evidence against a threshold or
      level of confidence. Individuals vary widely in response times even when they
      perform a simple task in the laboratory. We examine the neural bases of this
      individual variation by combining computational modeling and brain imaging of 64
      healthy adults performing a stop signal task. Behavioral performance was modeled
      by an accumulator model that describes the process of information growth to reach
      a threshold to respond. In this model, go trial reaction time (goRT) is jointly
      determined by the information growth rate, threshold, and movement time (MT). In
      a linear regression of activations in successful go and all stop (Go+Stop) trials
      against goRT across participants, the insula, supplementary motor area (SMA), pre
      SMA, thalamus including the subthalamic nucleus (STN), and caudate head respond
      to increasing goRT. Among these areas, the insula, SMA, and thalamus including
      the STN respond to a slower growth rate, the caudate head responds to an elevated
      threshold, and the pre-SMA responds to a longer MT. In the regression of Go+Stop
      trials against the stop signal reaction time (SSRT), the pre-SMA shows a negative
      correlation with SSRT. These results characterize the component processes of
      decision making and elucidate the neural bases of a critical aspect of inter
      subject variation in human behavior. These findings also suggest that the pre-SMA
      may play a broader role in response selection and cognitive control rather than
      simply response inhibition in the stop signal task.

PMID- 24027124
TI  - Colorless multifunctional coatings inspired by polyphenols found in tea,
      chocolate, and wine.

PMID- 24027125
TI  - Biocatalytically triggered co-assembly of two-component core/shell nanofibers.
AB  - For the development of applications and novel uses for peptide nanostructures,
      robust routes for their surface functionalization, that ideally do not interfere
      with their self-assembly properties, are required. Many existing methods rely on
      covalent functionalization, where building blocks are appended with functional
      groups, either pre- or post-assembly. A facile supramolecular approach is
      demonstrated for the formation of functionalized nanofibers by combining the
      advantages of biocatalytic self-assembly and surfactant/gelator co-assembly. This
      is achieved by enzymatically triggered reconfiguration of free flowing micellar
      aggregates of pre-gelators and functional surfactants to form nanofibers that
      incorporate and display the surfactants' functionality at the surface.
      Furthermore, by varying enzyme concentration, the gel stiffness and
      supramolecular organization of building blocks can be varied. 

PMID- 24027126
TI  - Fractal analysis of spontaneous fluctuations of the BOLD signal in the human
      brain networks.
AB  - PURPOSE: To investigate what extent brain regions are continuously interacting
      during resting-state, independent component analyses (ICA) was applied to analyze
      resting-state functional MRI (RS-fMRI) data. According to the analyzed results,
      it was surprisingly found that low frequency fluctuations (LFFs), which belong to
      the 1/f signal (a signal with power spectrum whose power spectral density is
      inversely proportional to the frequency), have been classified into groups using
      ICA; furthermore, the spatial distributions of these groups within the brain were
      found to resemble the spatial distributions of different networks, which
      manifests that the signal characteristics of RS LFFs are distinct across
      networks. In our work, we applied the 1/f model in the fractal analyses to
      further investigate this distinction. MATERIALS AND METHODS: Twenty healthy
      participants got involved in this study. They were scanned to acquire the RS-fMRI
      data. The acquired data were first processed with ICA to obtain the networks of
      the resting brain. Afterward, the blood-oxygenation level dependent (BOLD)
      signals of these networks were processed with the fractal analyses for obtaining
      the fractal parameter alpha. RESULTS: alpha was found to significantly vary
      across networks, which reveals that the fractal characteristic of LFFs differs
      across networks. According to prior literatures, this difference could be brought
      by the discrepancy of hemodynamic response amplitude (HRA) between networks.
      Hence, in our work, we also performed the computational simulation to discover
      the relationship between alpha and HRA. Based on the simulation results, HRA is
      highly linear-correlated with the fractal characteristics of LFFs which is
      revealed by alpha. CONCLUSION: Our results support that the origin of RS-fMRI
      signals contains arterial fluctuations. Hence, in addition to the commonly used
      method such as synchrony analysis and power spectral analysis, another approach,
      the fractal analysis, is suggested for acquiring the information of hemodynamic
      responses by means of RS-fMRI data.

PMID- 24027127
TI  - Biological behavior of fibroblast on contractile collagen hydrogel crosslinked by
      gamma-irradiation.
AB  - Collagen hydrogels exhibited a contractile trend in simulated body fluid. In this
      study, the internal pore architecture and mechanical properties of collagen
      hydrogel prepared by radiation crosslinking was evaluated during contraction, and
      the effect of contractile collagen hydrogels on the biological behavior of
      fibroblasts were investigated in vitro, such as viability, proliferation,
      morphology, apoptosis, cycle, and stress fiber. The results showed that accompany
      with contraction of collagen hydrogel, the pore diameter of the hydrogels
      decreased and compressive modulus increased. However, fibroblasts can grow on
      contractile collagen hydrogels. Indeed, collagen hydrogel contracted from
      circumference to the interior, which retard the spreading of fibroblasts on the
      dynamic substrate and interrupted the initial attachment of the cell. However,
      contraction of collagen hydrogel had not only significant influence on the L929
      cell proliferation, but also accelerated the apoptosis. Cell cycle analysis
      showed that contractile collagen hydrogel may promote cell cycle from G0/G1 phase
      to S phase, and DNA synthesis and cell proliferation were enhanced, but which may
      be different in contraction process. Therefore, as a scaffold for tissue
      engineering, the strategy for inhibition of the contraction of collagen hydrogel
      should be taken into account.

PMID- 24027128
TI  - Reintroduction medicine: whooping cranes in Wisconsin.
AB  - This paper presents veterinary management strategies and diagnostic findings in
      the reintroduction of the endangered whooping crane (Grus americana). Between
      2005 and 2010, 63 (27 male, 36 female) hatchling whooping cranes were assigned to
      a reintroduction project involving autumn release of costume-reared chicks in
      Wisconsin. Veterinary care included preventive measures and comprehensive pre
      release evaluations to improve fitness and reduce translocation of potential
      disease agents to native habitats. A total of 44 clinically normal birds were
      released (70% of assigned individuals). Cases of morbidity were classified
      according to primary body system affected. Musculoskeletal disorders were
      described in 57 birds (90%); five birds were removed from the project prior to
      release (8%), all for abnormalities that prevented normal function. Fourteen
      birds died or were euthanized prior to release (22%); pre-release mortality was
      attributed to developmental abnormality, predation, trauma or infectious disease.
      Chronic respiratory aspergillosis, diagnosed in seven birds (11%), was the most
      common infectious disease of concern. Predation and trauma were primary causes of
      post-release mortality; no evidence of infectious disease of captive origin was
      detected in the study population by the end of 2010. The assessment of data
      accumulated by this project helped to outline successful health management
      strategies, as well as identify and mitigate ongoing risks to captive whooping
      cranes that impede reintroduction efforts and achieving management goals for
      species recovery.

PMID- 24027129
TI  - Thoracic stent graft versus surgery for thoracic aneurysm.
AB  - BACKGROUND: Thoracic aortic aneurysm (TAA) is an uncommon disease with an
      incidence of 10.4 per 100,000 inhabitants. It occurs mainly in older individuals
      and is evenly distributed among both sexes. There are no signs or symptoms
      indicative of the presence of the disease. Progressive but unpredictable
      enlargement of the dilated aorta is the natural course of the disease and can
      lead to rupture. Open chest surgical repair using prosthetic graft interposition
      has been a conventional treatment for TAAs. Despite improvements in surgical
      procedures perioperative complications remain significant. The alternative option
      of thoracic endovascular aneurysm repair (TEVAR) is considered a less invasive
      and potentially safer technique, with lower morbidity and mortality compared with
      conventional treatment. Evidence is needed to support the use of TEVAR for these
      patients, rather than open surgery. OBJECTIVES: The aim of this review is to
      assess the efficacy of TEVAR versus conventional open surgery in patients with
      TAAs. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases
      Group Trials Search Co-ordinator searched the Specialised Register (last searched
      March 2013) and CENTRAL (2013, Issue 2). SELECTION CRITERIA: Randomised
      controlled trials in which patients with TAAs were randomly assigned to TEVAR or
      open surgical repair. DATA COLLECTION AND ANALYSIS: Two review authors
      independently identified and evaluated potential trials for eligibility. Excluded
      studies were further checked by another author. We did not perform any
      statistical analyses as no randomised controlled trials were identified. MAIN
      RESULTS: We did not find any published or unpublished randomised controlled
      trials comparing TEVAR with conventional open surgical repair for the treatment
      of thoracic aortic aneurysms. AUTHORS' CONCLUSIONS: Though stent grafting of the
      thoracic aorta is technically feasible and non-randomised studies suggest
      reduction of early outcomes such as paraplegia, mortality and hospital stay, high
      quality randomised controlled trials assessing all clinically relevant outcomes
      including open-conversion, aneurysm exclusion, endoleaks, and late mortality are
      needed.

PMID- 24027131
TI  - Multiple time scales in multi-state models.
AB  - In multi-state models, it has been the tradition to model all transition
      intensities on one time scale, usually the time since entry into the study
      ('clock-forward' approach). The effect of time since an intermediate event has
      been accommodated either by changing the time scale to time since entry to the
      new state ('clock-back' approach) or by including the time at entry to the new
      state as a covariate. In this paper, we argue that the choice of time scale for
      the various transitions in a multi-state model should be dealt with as an
      empirical question, as also the question of whether a single time scale is
      sufficient. We illustrate that these questions are best addressed by using
      parametric models for the transition rates, as opposed to the traditional Cox
      model-based approaches. Specific advantages are that dependence of failure rates
      on multiple time scales can be made explicit and described in informative
      graphical displays. Using a single common time scale for all transitions greatly
      facilitates computations of probabilities of being in a particular state at a
      given time, because the machinery from the theory of Markov chains can be
      applied. However, a realistic model for transition rates is preferable,
      especially when the focus is not on prediction of final outcomes from start but
      on the analysis of instantaneous risk or on dynamic prediction. We illustrate the
      various approaches using a data set from stem cell transplant in leukemia and
      provide supplementary online material in R.

PMID- 24027132
TI  - Conversion of trans-diboran(4)yl platinum complexes into their cis-bisboryl
      analogues.
AB  - The diboran(4)yl trans-[(iPr3 P)2 Pt(Br){B(NMe2 )B(NMe2 )Br}] (1) is readily
      converted into its cis-bisboryl analogues 2 and 3 by reaction with the chelating
      bisphosphines 1,2-bis(dicyclohexylphosphino)ethane (dcpe) and 1,1
      bis(dicyclohexylphosphino)methane (dcpm), respectively. A plausible mechanism of
      this transformation consists of a sequence of reductive diborane(4) elimination
      and subsequent reoxidative addition of its B?B bond to the low-valent platinum
      centers. Thus, the forced cis configuration of the phosphine ligands induces a
      change in the preferred reaction site of the diborane(4) with respect to
      oxidative addition. The reactions proceed with high selectivities, and the cis
      bisboryl complexes 2 and 3 were isolated in moderate yields (55 and 46 %).
      Moreover, their identity was clearly verified by NMR spectroscopy and X-ray
      diffraction studies. 

PMID- 24027133
TI  - Angular correction related to excision of specific cords in fasciectomy for
      Dupuytren's disease.
AB  - Named cords were excised sequentially at fasciectomy for Dupuytren's disease and
      the resultant correction in the joint angle was measured intra-operatively in 99
      fingers. Eighty-two metacarpophalangeal and 59 proximal interphalangeal joints
      were affected. At the metacarpophalangeal joint, excision of the central cord
      resulted in 82% correction in 69 joints, and spiral/lateral cord excision
      resulted in an additional 12% correction in 10 joints. At the proximal
      interphalangeal joint, excision of the central cord resulted in 44% correction in
      36 joints, spiral/lateral cord excision resulted in an additional 19% correction
      in 16 joints, and retrovascular cord excision resulted in a further 23%
      correction in 27 joints. Subsequent division of the accessory collateral ligament
      resulted in a further 14% correction in 14 joints. Larger pre-operative angles of
      the proximal interphalangeal joint were associated with a retrovascular cord, and
      larger combined angles were associated with an increasing number of pathological
      structures involved. The data explain the complexity of surgery at the proximal
      interphalangeal joint, where four structures are implicated in causing flexion
      deformity. 

PMID- 24027134
TI  - On the history and definition of Preiser's disease.
AB  - In 1910, Georg Preiser (1876-1913) described five cases of rarifying osteitis.
      Based on his imaging studies, he diagnosed post-traumatic avascular necrosis
      (AVN) of the scaphoid without any sign of primary fracture. This was followed by
      an article in 1911 in which Preiser related his findings to Kienbock's disease
      and Kohler's disease of the tarsal navicular. Upon searching the literature, we
      found descriptions and discussions of Preiser's imaging; however, the original
      images have never been published. We reproduce Preiser's original imaging in this
      current review. All of these appear to show a fracture and no signs of AVN,
      suggesting that Georg Preiser misinterpreted his findings. There is no apparent
      uniformity in the literature regarding the definition, description, or aetiology
      of Preiser's disease, and it is for this reason that we find the use of eponyms
      to be confusing. 

PMID- 24027135
TI  - How repeatable is two-finger tightness when used to tighten bone screws?

PMID- 24027136
TI  - Effects of dietary transgenic poplar leaf pellets on performance and tissues in
      rabbits.
AB  - BACKGROUND: Various studies have been conducted to evaluate the effect of Bt
      crops on animals. Insect-resistant bioassays have revealed that the chitinase
      BmkIT combination could be used as a new pest-resistant gene source and might be
      a complementary alien gene source to the Bt toxin gene. So it is necessary to
      assay the effects of chitinase-BmkIT plants on animals. RESULTS: Forty 40-day old
      New Zealand White Rabbits (Oryctolagus cuniculus) were fed for 60 consecutive
      days with formulated feed containing dehydrated poplar (Populus cathayana Rehd)
      leaves harbouring chitinase-BmkIT gene combination or untransformed counterparts,
      and the potential toxicological effects of transgenic leaves on rabbits were
      explored. The results of the growth study revealed no significant differences for
      daily weight gain, feed intake and feed conversion ratio where they were 101.6%,
      99.2% and 97.8% of the treatment compared to the control, respectively. No
      obvious pathological change was observed in the small intestine, stomach, spleen,
      kidney, lung, heart, bladder, pancreas, prostate and ovary. Electron microscopy
      observations of liver cells and renal cells showed they were both normal in the
      two groups. No feed-derived chitinase, BmkIT and NPTII genes were found in small
      intestine, blood, or leg muscle samples although they were detected in the
      formulated feed. CONCLUSION: We conclude that the processed poplar leaves with
      foreign chitinase-BmkIT genes had no obviously harmful effects on rabbits.

PMID- 24027139
TI  - Highly efficient photocatalytic water reduction with robust iridium(III)
      photosensitizers containing arylsilyl substituents.
AB  - Waterproof complexes: Cationic Ir(III) photosensitizers (PSs) with an ancillary
      4,4'-bis(4-(triphenylsilyl)phenyl)-2,2'-bipyridine ligand enabled hydrogen
      evolution from water with high turnover numbers (TONs; see scheme). The
      peripheral triphenylsilyl moieties prevent ligand substitution by solvent
      molecules, such as water, and thus increase the durability of the complexes.
      SR=sacrificial reducing agent, WRC=water-reduction catalyst. 

PMID- 24027138
TI  - Design and validation of a dynamic cell-culture system for bone biology research
      and exogenous tissue-engineering applications.
AB  - Bone lacunocanalicular fluid flow ensures chemotransportation and provides a
      mechanical stimulus to cells. Traditional static cell-culture methods are ill
      suited to study the intricacies of bone biology because they ignore the three
      dimensionality of meaningful cellular networks and the lacunocanalicular system;
      furthermore, reliance on diffusion alone for nutrient supply and waste product
      removal effectively limits scaffolds to 2-3 mm thickness. In this project, a flow
      perfusion system was custom-designed to overcome these limitations: eight
      adaptable chambers housed cylindrical cell-seeded scaffolds measuring 12 or 24 mm
      in diameter and 1-10 mm in thickness. The porous scaffolds were manufactured
      using a three-dimensional (3D) periodic microprinting process and were composed
      of hydroxyapatite/tricalcium phosphate with variable thicknesses, strut sizes,
      pore sizes and structural configurations. A multi-channel peristaltic pump drew
      medium from parallel reservoirs and perfused it through each scaffold at a
      programmable rate. Hermetically sealed valves permitted sampling or replacement
      of medium. A gas-permeable membrane allowed for gas exchange. Tubing was selected
      to withstand continuous perfusion for > 2 months without leakage. Computational
      modelling was performed to assess the adequacy of oxygen supply and the range of
      fluid shear stress in the bioreactor-scaffold system, using 12 * 6 mm scaffolds,
      and these models suggested scaffold design modifications that improved oxygen
      delivery while enhancing physiological shear stress. This system may prove useful
      in studying complex 3D bone biology and in developing strategies for engineering
      thick 3D bone constructs. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24027137
TI  - Long-term neurobiological consequences of early postnatal hCMV-infection in
      former preterms: a functional MRI study.
AB  - Early postnatal infection with human cytomegalovirus (hCMV) may contribute to an
      adverse cognitive outcome in early preterm-born children (PT). We here set out to
      explore whether long-term neurobiological consequences of such an infection are
      detectable using fMRI in children and adolescents who were born very preterm and
      who either did (PThCMV+ ) or did not (PT(hCMV-)) suffer from an early postnatal
      hCMV-infection, when compared with typically developing healthy control (HC)
      subjects. Overall, data from 71 children and adolescents could be included, 34 PT
      (of which 15 were PT(hCMV+) and 19 were PT(hCMV-)) and 37 HC. Using a recently
      established "dual use" fMRI task, we investigated language and visuospatial
      functions. There were significant activation differences in the left hippocampus
      (PT > HC and PT(hCMV+) > HC), and in the right anterior cingulate cortex (PT(hCMV
      ) > PT(hCMV+)) when performing the language task. Surprisingly, only a small
      region in the occipital cortex showed a significant activation difference (HC >
      PT(HCMV-)) when performing the visuospatial task. Targeted analyses revealed
      differences in gray matter volume, but not density, in several brain regions. Our
      results suggest that long-term neurobiological consequences of an early postnatal
      hCMV infection are detectable even in older children and adolescents formerly
      born very preterm, compatible with a higher effort when performing a cognitive
      task. This suggests that measures to prevent such an infection are warranted.
      Furthermore, an interrelation of brain structure and function was detected that
      may constitute a severe confound when using fMRI to compare structurally
      differing groups.

PMID- 24027140
TI  - Validation of claims-based algorithms for identification of high-grade cervical
      dysplasia and cervical cancer.
AB  - BACKGROUND: High-grade cervical dysplasia or cervical intraepithelial neoplasia
      grade 2 or worse has been widely used as a surrogate endpoint in cervical cancer
      screening or prevention trials. METHODS: To identify high-grade cervical
      dysplasia and cervical cancer, we developed claims-based algorithms that
      incorporated a combination of diagnosis and procedure codes using the billing
      data in an electronic medical records database and assessed the validity of the
      algorithms in an independent administrative claims database. We calculated the
      positive predictive value (PPV) with the 95% confidence interval (CI) of each
      algorithm, using new cytologic or pathologic diagnosis of cervical
      intraepithelial neoplasia 2 or 3, carcinoma in situ, or cervical cancer as the
      gold standard. RESULTS: Having >=1 diagnosis code for high-grade cervical
      dysplasia or cervical cancer had a PPV of 57.1% (95%CI, 54.7-59.5%). By requiring
      >=2 diagnoses for high-grade cervical dysplasia or cervical cancer, separated by
      7-30 days, the PPV increased to 60.2% (95%CI, 53.9-66.1%). At least two diagnoses
      and a procedure code within a month from the first diagnosis date yielded a PPV
      of 80.7% (95%CI, 73.6-86.2%). The algorithms had greater PPVs in identifying
      prevalent high-grade cervical dysplasia or cervical cancer. Overall, the PPVs of
      these algorithms were similar or slightly lower in the external claims data than
      in the sample used to derive the algorithms. CONCLUSIONS: Use of >=2 diagnosis
      codes in combination with a procedure code appears to be a valid tool for
      studying high-grade cervical dysplasia and cervical cancer in both electronic
      medical record and administrative claims databases.

PMID- 24027141
TI  - The Cochrane Collaboration and its worldwide contributions to anaesthesia
      research and care.

PMID- 24027142
TI  - Linking pay and performance.

PMID- 24027143
TI  - Intraoperative awareness: a pound of prevention, an ounce of cure?

PMID- 24027145
TI  - Extracorporeal membrane oxygenation in brain-death organ and tissues donors: a
      single-centre experience.

PMID- 24027144
TI  - Perioperative database research: possibilities and pitfalls.

PMID- 24027146
TI  - A note from the future.

PMID- 24027147
TI  - General anaesthesia with laryngeal mask airway may cause recurrence of
      pneumocephalus in a patient with head injury.

PMID- 24027148
TI  - Assessment of anaesthetists' ability to predict difficulty of bag-mask
      ventilation.

PMID- 24027149
TI  - Arterial punctures in small children.

PMID- 24027150
TI  - Simplified measures of postoperative nausea and vomiting do not transfer to other
      populations.

PMID- 24027151
TI  - Effects of an intraoperative infusion of 4% succinylated gelatine (Gelofusine)
      and 6% hydroxyethyl starch (Voluven) on blood volume.

PMID- 24027152
TI  - Reply from the authors.

PMID- 24027153
TI  - Haemodilution made difficult.

PMID- 24027154
TI  - Reply from the authors.

PMID- 24027161
TI  - Preparation and loading buffer study of polyvinyl alcohol-based immobilized Ti4+
      affinity chromatography for phosphopeptide enrichment.
AB  - Despite recent advances in phosphoproteomics, an efficient and simple enrichment
      protocol is still a challenge and of high demand aiming at large-scale plant
      phosphoproteomics studies. Here, we developed a novel loading buffer system for
      synthesized immobilized metal affinity chromatography material targeting plant
      samples, which was prepared by a simple one-step esterification between polyvinyl
      alcohol and phosphoric acid and then was subjected to immobilize Ti(4+). SEM and
      Fourier transform IR spectroscopy were used to assure the synthesis protocol of
      the polyvinyl alcohol-based Ti(4+) immobilized material, and the specific surface
      areas and pore volumes of the polymers were measured. The selectivity for
      phosphopeptide enrichment from alpha-casein was improved by optimizing the pH and
      components of the loading buffer. By using potassium hydrogen
      phthalate/hydrochloric acid with pH at 2.50 as the loading buffer, 19
      phosphopeptides with high intensity were identified. The final optimized protocol
      was adapted to salt-stressed maize leaves for phosphoproteome analysis. A total
      of 57 phosphopeptides containing 59 phosphorylated sites from 50 phosphoproteins
      were identified in salt-stressed maize leaf. The research was meaningful to
      obtain much more information about phosphoproteins leading to the comprehension
      of salt resistance and salt-inducible phosphorylated processes of maize leaves.

PMID- 24027162
TI  - Perioperative fluid volume optimization following proximal femoral fracture.
AB  - BACKGROUND: Proximal femoral fracture (PFF) is a common orthopaedic emergency,
      affecting mainly elderly people at high risk of complications. Advanced methods
      for managing fluid therapy during treatment for PFF are available, but their role
      in reducing risk is unclear. OBJECTIVES: To compare the safety and effectiveness
      of different methods of perioperative fluid optimization in adult participants
      undergoing surgical repair of hip fracture. We considered the following methods:
      advanced invasive haemodynamic monitoring, such as transoesophageal Doppler and
      pulse contour analysis; a protocol using standard measures, such as blood
      pressure, urine output and central venous pressure; and usual care.Comparisons of
      fluid types (e.g. crystalloid vs colloid) and other methods of optimizing oxygen
      delivery, such as blood product therapies and pharmacological treatment with
      inotropes and vasoactive drugs, are considered elsewhere. SEARCH METHODS: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2012, Issue 9); MEDLINE (1966 to October 2012); and EMBASE (1980
      to October 2012) without language restrictions. We ran forward and backward
      citation searches on identified trials. We contacted authors and searched
      ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform
      for unpublished trials. This is an updated version of a review published in 2004.
      The original search was performed in October 2003. SELECTION CRITERIA: We
      included randomized controlled trials (RCTs) in adult participants undergoing
      surgical treatment for PFF, which compared any two of advanced haemodynamic
      monitoring, protocols using standard measures or usual care, irrespective of
      blinding, language or publication status. DATA COLLECTION AND ANALYSIS: Two
      review authors assessed the impact of fluid optimization interventions on
      outcomes of mortality, length of hospital stay, return of participant to pre
      fracture accommodation and mobility at six months and adverse events in hospital.
      We pooled data using risk ratio or mean difference for dichotomous or continuous
      data, respectively, based on random-effects models. MAIN RESULTS: We included
      three RCTs with a total of 200 participants. One of these included studies was
      found to have a high risk of bias; no trial featured all pre-specified outcomes.
      We found one trial for which data are awaited for classification and two ongoing
      trials. One included study with low risk of bias found that compared with usual
      care, time to medical fitness for discharge was shorter with the use of advanced
      haemodynamic monitoring (mean reduction 6.20 days, 95% CI 2.3 to 10.1 days; 59
      participants, one trial) and with the use of protocols that apply standard
      measures (mean reduction 3.9 days, 95% CI 0.75 to 7.05; 57 participants, one
      trial). Our results are consistent with both increased and decreased risk of
      mortality and adverse events in participants receiving the intervention. No data
      for other outcomes were available. Our results are limited by the quantity of
      available data. AUTHORS' CONCLUSIONS: Three studies considering a total of 200
      participants reveal an absence of evidence that fluid optimization strategies
      improve outcomes for participants undergoing surgery for PFF. Length of hospital
      stay may be improved, but lack of good quality data leaves uncertainty. Further
      research powered to test some of these outcomes is ongoing.

PMID- 24027163
TI  - Norbornenes in inverse electron-demand Diels-Alder reactions.
AB  - Significant differences in the reactivity of norbornene derivatives in the
      inverse electron-demand Diels-Alder reaction with tetrazines were revealed by
      kinetic studies. Substantial rate enhancement for the exo norbornene isomers was
      observed. Quantum-chemical calculations were used to rationalize and support the
      observed experimental data. 

PMID- 24027164
TI  - An optimal multi-period crossover design for an application in paediatric
      nephrology.
AB  - Crossover clinical trials can provide substantial benefits by eliminating inter
      patient variation from treatment comparisons and by allowing multiple
      observations of each patient. They are particularly useful when sample sizes are
      necessarily small. These advantages proved particularly valuable in an assessment
      of clot prevention in children undergoing haemodialysis. Only small numbers of
      children are treated at any given time in any single dialysis unit, but each
      patient is obliged to attend two or three times each week, suggesting the use of
      a crossover trial with many periods. Standard crossover trials described in the
      literature (i) typically have fewer than 10 periods and (ii) are based on a model
      of questionable applicability to this study. This paper describes the derivation
      of an optimal crossover trial with 30 periods, which was used to compare two
      anticoagulants using nine patients. There is also a discussion of the analysis of
      the data obtained in the trial, which had a distribution markedly different from
      that anticipated when the study was designed.

PMID- 24027165
TI  - Macrophages behavior on different NIPAm-based thermoresponsive substrates.
AB  - Thermoresponsive materials and surfaces are widely used in cell culture
      applications. There is a lot of research work employing thermoresponsive
      materials with various structure and compositions. However, little is known about
      the immunological response to the thermoresponsive materials. Macrophage-like
      transformed murine cell line RAW264.7 was selected as it is a widely used
      standard model for immune activation analysis. This study proposes to compare the
      effects of thermoresponsive films with various compositions on macrophage cells.
      Thermoresponsive materials are a useful utility as a non-enzymatic harvesting
      system for tissue culture. As RAW264.7 cells are difficult to remove from the
      substrate by enzymatic methods we also explored the possibility to use
      thermoresponsive materials for the macrophage cultivation. Spin coating and
      solvent casting was used to produce films of N-isopropylacrylamide-based polymers
      from the nanometer to micrometer range. Successful cell adhesion and
      proliferation was highly dependent on the thickness and composition of the
      coating. RAW264.7 cells were successfully detached from the coatings upon
      temperature reduction. Furthermore, results indicate that the RAW264.7 cells
      remained inactivated as cell secreted cytokine remained at a low level and the
      surface receptor profile of RAW264.7 was not altered when cells were detached in
      this manner.

PMID- 24027166
TI  - Predictors of coupling between structural and functional cortical networks in
      normal aging.
AB  - Understanding how the mammalian neocortex creates cognition largely depends on
      knowledge about large-scale cortical organization. Accumulated evidence has
      illuminated cortical substrates of cognition across the lifespan, but how
      topological properties of cortical networks support structure-function
      relationships in normal aging remains an open question. Here we investigate the
      role of connections (i.e., short/long and direct/indirect) and node properties
      (i.e., centrality and modularity) in predicting functional-structural
      connectivity coupling in healthy elderly subjects. Connectivity networks were
      derived from correlations of cortical thickness and cortical glucose consumption
      in resting state. Local-direct connections (i.e., nodes separated by less than 30
      mm) and node modularity (i.e., a set of nodes highly interconnected within a
      topological community and sparsely interconnected with nodes from other modules)
      in the functional network were identified as the main determinants of coupling
      between cortical networks, suggesting that the structural network in aging is
      mainly constrained by functional topological properties involved in the
      segregation of information, likely due to aging-related deficits in functional
      integration. This hypothesis is supported by an enhanced connectivity between
      cortical regions of different resting-state networks involved in sensorimotor and
      memory functions in detrimental to associations between fronto-parietal regions
      supporting executive processes. Taken collectively, these findings open new
      avenues to identify aging-related failures in the anatomo-functional organization
      of the neocortical mantle, and might contribute to early detection of prevalent
      neurodegenerative conditions occurring in the late life.

PMID- 24027167
TI  - Primary mediastinal sarcoma: surgical outcomes of 21 cases.
AB  - OBJECTIVES: Primary sarcomas of the mediastinum are relatively rare. This article
      reviews the surgical outcomes of 21 cases diagnosed with localized mediastinal
      sarcomas receiving multidisciplinary treatment modalities in Sichuan province,
      China, from January 1996 to January 2011. METHODS: Twenty-one cases of
      histologically diagnosed primary mediastinal sarcoma undergoing surgical
      treatment were reviewed retrospectively. Disease-free survival (DFS) and overall
      survival (OS) were statistically analysed. All the patients presented with
      localized tumours consisting of 5 females and 16 males with a median age of 41.0
      years (range: 9.0-68.0 years). Among all cases, 17 (81.0%) had an Eastern
      Cooperative Oncology Group performance status score of <=1 at diagnosis. Eight
      (38.1%) underwent macroscopically complete resection (R0-R1) and 13 (61.9%) had
      incomplete resection (R2). Ten (47.6%) received postoperative radiotherapy and 7
      (33.3%) postoperative chemotherapy. RESULTS: The median DFS was 17 months (range:
      0.4-79.8 months) and the median OS was 27.2 months (range: 0.4-79.8 months).
      Patients receiving complete resection showed significantly improved DFS (P =
      0.031) and OS (P = 0.035) compared with those with incomplete resection. Neither
      postoperative radiotherapy nor chemotherapy significantly improved DFS (P =
      0.770, P = 0.756) or OS (P = 0.905, P = 0.738). However, 7 patients (R2) and 2
      (R0-R1 and grade 3) had improved local control with a local recurrence-free
      survival of 28.9 months (range: 7.6-73.2 months). CONCLUSIONS: Complete resection
      should be preferentially attempted compared with incomplete resection and
      postoperative radiotherapy might yield good local control.

PMID- 24027168
TI  - Gold nanoclusters with enhanced tunable fluorescence as bioimaging probes.
AB  - Development of unique bioimaging probes offering essential information's about
      bio environments are an important step forward in biomedical science.
      Nanotechnology offers variety of novel imaging nanoprobes having high-photo
      stability as compared to conventional molecular probes which often experience
      rapid photo bleaching problem. Although great advances have been made on the
      development of semiconductor nanocrystals-based fluorescent imaging probes,
      potential toxicity issue by heavy metal component limits their in vivo
      therapeutic and clinical application. Recent works show that fluorescent gold
      clusters (FGCs) can be a promising nontoxic alternative of semiconductor
      nanocrystals. FGCs derived imaging nanoprobes offer stable and tunable visible
      emission, small hydrodynamic size, high biocompatibility and have been exploited
      in variety in vitro and in vivo imaging applications. In this review, we will
      focus on the synthetic advances and bioimaging application potentials of FGCs. In
      particular, we will emphasize on functional FGCs that are bright and stable
      enough to be useful as bioimaging probes.

PMID- 24027169
TI  - A tradeoff analysis of risk cutoffs for the quadruple serum screen for Down
      syndrome.
AB  - OBJECTIVES: In maternal serum screening for Down syndrome, a cutoff of 1 : 270 is
      often used as a decision point to recommend invasive confirmatory testing.
      However, it has not been established how well this or any other cutoff relates to
      patient preferences, that is, the values that pregnant women attach to various
      screening outcomes. The purpose of this study was to examine the clinical and
      economic tradeoffs of a wide range of risk cutoffs for the quadruple screen.
      METHODS: Screening costs and outcomes for multiple risk cutoffs were modeled
      using a Monte Carlo simulation. RESULTS: The optimal cutoff for maternal serum
      screening depends on the relative values placed by the patient on different
      outcomes. Total societal costs were similar across the range of cutoffs.
      CONCLUSIONS: Given that different screening outcomes are optimized by different
      cutoff values, a one-size-fits-all approach may not be appropriate.

PMID- 24027171
TI  - Length-dependent charge generation from vertical arrays of high-aspect-ratio ZnO
      nanowires.
AB  - Aqueous chemical growth of zinc oxide nanowires is a flexible and effective
      approach to obtain dense arrays of vertically oriented nanostructures with high
      aspect ratio. Herein we present a systematic study of the different synthesis
      parameters that influence the ZnO seed layer and thus the resulting morphological
      features of the free-standing vertically oriented ZnO nanowires. We obtained a
      homogeneous coverage of transparent conductive substrates with high-aspect-ratio
      nanowire arrays (length/diameter ratio of up to 52). Such nanostructured vertical
      arrays were examined to assess their electric and piezoelectric properties, and
      showed an electric charge generation upon mechanical compressive stress. The
      principle of energy harvesting with these nanostructured ZnO arrays was
      demonstrated by connecting them to an electronic charge amplifier and storing the
      generated charge in a series of capacitors. We found that the generated charge
      and the electrical behavior of the ZnO nanowires are strictly dependent on the
      nanowire length. We have shown the importance of controlling the morphological
      properties of such ZnO nanostructures for optimizing a nanogenerator device. 

PMID- 24027172
TI  - Introduction: Microsurgery in China.

PMID- 24027170
TI  - Cost estimation of first-line antiretroviral therapy with zidovudine/stavudine as
      the nucleoside backbone in India: a pilot study.
AB  - BACKGROUND: In India, a zidovudine-based regimen is preferred as the first-line
      drug treatment for HIV, despite high rates of drug toxicity. This study estimates
      the treatment costs for HIV. METHODS: Eligible patients were enrolled from
      Antiretroviral Therapy Center, Christian Medical College, India. Baseline
      demographic and clinical characteristics, medical and nonmedical expenditure, and
      lost income were collected. RESULTS: Of 41 patients enrolled and followed for 6
      months, HIV treatment toxicity and opportunistic infections were reported by 12
      (29%) and 13 (31.7%) patients, respectively. The median total costs, direct
      costs, and out-of-pocket expenditure were Indian rupees (INR) 9418 (US$181), 8727
      (US$168), and 7157 (US$138), respectively. Diagnostic tests accounted for 58% of
      the expenses. HIV treatment accounted for 34% of the median income earned INR 21
      000 (US$404). Expenditure for treatment with toxicity was 44% higher than without
      toxicity. CONCLUSION: Current treatment is associated with toxicity, increasing
      treatment costs and imposing a significant economic burden.

PMID- 24027173
TI  - Prenatal diagnosis and management of a massive fetal ovarian hemorrhagic cyst
      torsion with secondary fetal anemia.
AB  - We report the case of one of the largest prenatally detected fetal hemorrhagic
      cyst with ovarian torsion and fetal anemia leading to subsequent cesarean section
      delivery and further unilateral oophorectomy of the neonate. Usually, fetal
      ovarian cysts tend to resolve spontaneously within the first months after birth.
      There is no need of surgical treatment for such simple cysts. Routine sonographic
      examinations are obligatory, because in some cases complications such as massive
      hemorrhage, cyst rupture, or ovarian torsion with following infarction can occur.
      With the occurrence of these complex cyst signs by sonographic investigation,
      subsequent intervention should be considered by an interdisciplinary team.

PMID- 24027174
TI  - A practical access to highly enantiomerically pure flavanones by catalytic
      asymmetric transfer hydrogenation.
AB  - A surprisingly selective, non-enzymatic kinetic resolution of readily available,
      racemic beta-chiral ketones enabled the title process, which was applied to a
      rapid synthesis of several bioactive flavanones in virtually enantiopure form
      (see scheme; MOM=methoxymethyl, Ts=p-toluenesulfonyl). 

PMID- 24027175
TI  - Superposition of episodic memories: overdistribution and quantum models.
AB  - Memory exhibits episodic superposition, an analog of the quantum superposition of
      physical states: Before a cue for a presented or unpresented item is administered
      on a memory test, the item has the simultaneous potential to occupy all members
      of a mutually exclusive set of episodic states, though it occupies only one of
      those states after the cue is administered. This phenomenon can be modeled with a
      nonadditive probability model called overdistribution (OD), which implements
      fuzzy-trace theory's distinction between verbatim and gist representations. We
      show that it can also be modeled based on quantum probability theory. A quantum
      episodic memory (QEM) model is developed, which is derived from quantum
      probability theory but also implements the process conceptions of global matching
      memory models. OD and QEM have different strengths, and the current challenge is
      to identify contrasting empirical predictions that can be used to pit them
      against each other. 

PMID- 24027176
TI  - Differentiation of human bone marrow mesenchymal stem cells on decellularized
      extracellular matrix materials.
AB  - Mesenchymal bone marrow stromal cells may be a source of cells to preseed
      decellularized biologic mesh materials for improved cellularization and promote a
      more physiologic tissue after remodeling. Spontaneous differentiation of
      mesenchymal stromal cells on the decellularized material would be undesirable.
      Conversely, induced differentiation of mesenchymal stem cells (MSC) on the
      material would suggest that these materials may have promise as scaffold
      materials for bone, cartilage, or adipocyte formation. Two sources of mesenchymal
      cells were evaluated for induced differentiation in control wells. These MSCs
      were also evaluated for spontaneous or induced differentiation on decellularized
      porcine dermis and mesothelium materials. Primarily harvested bone marrow MSCs
      and commercially obtained MSCs were induced into osteoblasts and adipocytes on
      decellularized dermis and mesothelium materials. The MSCs were able to be induced
      into chondrocytes in pellet form but not when grown as a monolayer on the
      materials. The MSCs did not undergo spontaneous differentiation when grown on the
      materials for up to four weeks. MSC grown on decellularized porcine dermis or
      mesothelium do not spontaneously differentiate and may serve as a source of
      autologous cells for preseeding these extracellular matrix materials prior to
      implantation.

PMID- 24027177
TI  - Etodolac activates and desensitizes transient receptor potential ankyrin 1.
AB  - The transient receptor potential ankyrin 1 (TRPA1) channel is well known as a
      sensor to environmental irritant compounds, cold, and endogenous proalgesic
      agents. TRPA1 is expressed on sensory neurons and is involved in pain modulation.
      Etodolac is a cyclooxygenase (COX)-2 inhibitor that belongs to the class of
      nonsteroidal anti-inflammatory drugs (NSAIDs). A recent study indicates that
      etodolac inhibits allyl isothiocyanate (AITC)-induced calcium influx in
      heterologous HEK293 cells and sensory neurons. To examine whether and how
      etodolac modulates the TRPA1 channels, we applied etodolac to TRPA1-transfected
      HEK293 cells or rat dorsal root ganglion (DRG) neurons and recorded the currents
      using the whole-cell patch clamp technique. We found that etodolac at higher
      doses could activate and then desensitize TRPA1 channels in heterologous
      expressing HEK293 cells as well as in DRG neurons. The etodolac-induced currents
      were significantly attenuated in cysteine residues mutated human TRPA1
      transfected HEK293 cells. Interestingly, application of etodolac at drug plasma
      levels in clinical usage did not induce significant TRPA1 currents but reduced
      the subsequent AITC-induced currents to 25% in HEK293 cells expressing TRPA1.
      Moreover, no modulatory effect of etodolac on TRPA1 was detected in the cysteine
      mutant cells. These data indicate a novel mechanism of the anti-inflammatory and
      analgesic clinical effects of etodolac, which may be involved with its direct
      activation and the subsequent desensitization of TRPA1 through the covalent
      modification of cysteine residues.

PMID- 24027178
TI  - Protein nutrition mediates lean body mass homeostasis in the aging warfighter.
AB  - The demographic shift of the average age in the United States and worldwide
      mandates that careful attention be paid to the nutritional and health needs of
      all segments of our older adult population. Well-defined changes in body
      composition occur in aging animals and humans. Characteristic of this change is
      the age-associated decline in skeletal muscle mass, sarcopenia. Data from
      observational studies of dietary intake and body composition suggest that a
      substantial proportion of adults over the age of 60 y consume less than the U.S.
      recommended dietary allowance for protein and that greater dietary protein intake
      appears to reduce the decline in lean/muscle mass with aging. Studies of acute
      ingestion of high-quality dietary protein in healthy older adults suggest that
      the age-related blunting of protein synthetic capacity can be overcome with
      increased dietary protein intake. However, studies on chronic administration of
      high-quality protein supplements in cohorts of older adults are more equivocal
      with respect to improving or preserving muscle mass. This review highlights
      selective aspects of protein supplementation in older adults. 

PMID- 24027180
TI  - Protein supplementation for military personnel: a review of the mechanisms and
      performance outcomes.
AB  - Protein supplement use is common among athletes, active adults, and military
      personnel. This review provides a summary of the evidence base that either
      supports or refutes the ergogenic effects associated with different mechanisms
      that have been proposed to support protein supplementation. It was clear that if
      carbohydrate delivery was optimal either during or after an acute bout of
      exercise that additional protein will not increase exercise capacity. Evidence
      was also weak to substantiate use of protein supplements to slow the increase in
      brain serotonin and onset of central fatigue. It was also evident that additional
      research is warranted to test whether the benefits of protein supplements for
      enhancing recovery of fluid balance after exercise will affect subsequent work in
      the heat. In contrast, with repeated exercise, use of protein supplementation was
      associated with reductions in muscle soreness and often a faster recovery of
      muscle function due to reductions in protein degradation. There was also good
      supportive evidence for long-term benefits of protein supplementation for gains
      in muscle mass and strength through accelerated rates of protein synthesis, as
      long as the training stimulus was of sufficient intensity, frequency, and
      duration. However, studies have not examined the impact of protein supplements
      under the combined stress of a military environment that includes repeated bouts
      of exercise with little opportunity for feeding and recovery, lack of sleep, and
      exposure to extreme environments. Both additional laboratory and field research
      is warranted to help provide evidence-based guidance for the choice of protein
      supplements to enhance soldier performance. 

PMID- 24027179
TI  - Is there an optimal time for warfighters to supplement with protein?
AB  - Although nutritional requirements for warfighters will inevitably vary in
      accordance with job role and active-inactive duty cycling, somewhat generic
      recommendations do still apply. In considering aspects of "optimal" nutrient
      timing, it is important to outline singular and combinatorial relationships
      between protein intake and physical activity (e.g., exercise) in the context of
      the following: 1) skeletal muscle protein turnover, 2) functional recovery, and
      3) adaptation to exercise. The essential amino acid (EAA) components of dietary
      protein are key macronutrients regulating muscle proteostasis, because they
      provide substrate to replenish muscle proteins lost during fasted periods. This
      occurs through a substantial, albeit short-lived (~2 h) EAA-induced stimulation
      of muscle protein synthesis (MPS) and via an insulin-mediated suppression of
      muscle protein breakdown (MPB) (via carbohydrate- and/or EAA-mediated insulin
      secretory effects). At rest, intake of protein (optimal range between 20 and 40 g
      of high-quality protein, equating to ~10-20 g EAAs) every ~4-5 h is advocated due
      to the refractoriness of MPS in response to continuous supply. Bouts of exercise
      also stimulate muscle protein turnover (increasing both MPS and MPB), but in the
      absence of protein intake net muscle protein balance remains negative such that
      exercise alone is catabolic. Intake of dietary protein redresses this balance
      through enhancing both the amplitude and duration of exercise-induced increases
      in MPS while concomitantly limiting MPB. These postexercise periods of positive
      net protein balance permit muscle adaptation and functional recovery. Finally, in
      relation to exercise, protein dosing (at a minimum of ~20 g) both in close
      proximity to exercise and thereafter every 4-5 h during waking hours (including
      before bedtime) is likely optimal for adaptation/functional recovery. 

PMID- 24027181
TI  - Protein supplementation in U.S. military personnel.
AB  - Protein supplements (PSs) are, after multivitamins, the most frequently consumed
      dietary supplement by U.S. military personnel. Warfighters believe that PSs will
      improve health, promote muscle strength, and enhance physical performance. The
      estimated prevalence of regular PS use by military personnel is nearly 20% or
      more in active-duty personnel, which is comparable to collegiate athletes and
      recreationally active adults, but higher than that for average U.S. civilians.
      Although the acute metabolic effects of PS ingestion are well described, little
      is known regarding the benefits of PS use by warfighters in response to the
      metabolic demands of military operations. When dietary protein intake approaches
      1.5 g . kg(-1) . d(-1), and energy intake matches energy expenditure, the use of
      PSs by most physically active military personnel may not be necessary. However,
      dismounted infantry often perform operations consisting of long periods of
      strenuous physical activity coupled with inadequate dietary energy and protein
      intake. In these situations, the use of PSs may have efficacy for preserving fat
      free mass. This article reviews the available literature regarding the prevalence
      of PS use among military personnel. Furthermore, it highlights the unique
      metabolic stressors affecting U.S. military personnel and discusses potential
      conditions during which protein supplementation might be beneficial. 

PMID- 24027182
TI  - Considerations for protein supplementation in warfighters.
AB  - Ingestion of dietary protein stimulates the synthesis of numerous body proteins.
      This effect is manifest via hyperaminoacidemia with insulin as a permissive
      factor. In a sedentary person in energy balance, it is possible to maintain
      nitrogen balance while consuming protein at an intake of 0.8 g protein . kg(-1) .
      d(-1). What is unclear is whether being in nitrogen balance is optimal for
      protein synthesis and not merely adequate and representative of adaptive
      strategies that could lead to accommodation in "stressed" physiological states.
      It is clear that being in negative energy balance results in reductions in lean
      mass and reduced rates of protein synthesis, which can be mitigated by
      consumption of higher (i.e., 2-3 times the RDA) dietary protein. That long-term
      practice of inadequate protein intake leads to reduced metabolic, physiological,
      and physical function provides the basic rationale for the consumption of more
      than merely adequate protein to prevent not only adaptation but accommodation.
      Warfighters engaged in combat have been shown to have high daily physical
      activity energy expenditure, engage in voluntary energy restriction, and are
      under high metabolic and mental stress. Thus, as a group warfighters would be at
      risk of consuming suboptimal protein intakes and therefore may benefit from
      higher amounts of dietary protein intake. Balanced against the potential risk of
      consuming higher protein, the scientific documentation for which is lacking,
      there is a strong rationale for the recommendation of higher protein intakes in
      warfighters who are engaged in field operations. 

PMID- 24027183
TI  - Training table to the battlefield: protein recommendations for warfighters.
AB  - Warfighters represent a population of athletes for whom routine training and
      physical expectations for military operations parallel, and very often exceed,
      those of their civilian counterparts. Like athletes, warfighters require
      nutrition support to optimize physical condition to maintain training, sustain
      performance, speed recovery, and prevent injury and illness. Specifically, energy
      and protein requirements have been tailored for these populations. Like athletes,
      warfighters consider protein a critical component of their diet and often
      incorporate protein supplements into daily diet plans. This article highlights
      sports nutrition principles that target energy and protein needs of athletes,
      considers the basis of these recommendations in the context of protein
      supplementation, and asserts that translating these recommendations to the
      warfighter is appropriate and necessary. The recommended range of protein intake
      of 1.2-1.8 g . kg (- 1) . d (- 1) can be extended to the warfighter. Because
      energy balance is pivotal to optimal protein utilization, adequate energy intake
      or lack thereof such that a state of negative energy balance exists, should be
      given particular consideration for the warfighter. Routine protein
      supplementation is recommended to reduce protein breakdown, support protein
      synthesis, and promote a positive net protein balance throughout various
      deployment situations and when energy intake is insufficient. 

PMID- 24027184
TI  - Intakes of PUFAs were inversely associated with plasma C-reactive protein 12
      years later in a middle-aged population with vitamin E intake as an effect
      modifier.
AB  - Although n-3 (omega-3) polyunsaturated fatty acids (PUFAs) are considered anti
      inflammatory components, the role of dietary n-6 PUFAs in inflammation remains
      controversial. Some mechanistic evidence suggests vitamin E as a potential effect
      modifier in the relationship between PUFAs and inflammation. Our objectives were
      to evaluate the long-term associations between dietary intakes of PUFAs and
      elevated plasma C-reactive protein (CRP) and to investigate potential effect
      modification by vitamin E. Individuals in the placebo group of the SU.VI.MAX
      trial who had available CRP measurements in 2007-2009 were included in the study
      (n = 843). Dietary intakes of n-3 PUFAs, n-6 PUFAs, and vitamin E were assessed
      in 1994-1996 with at least 6 dietary records. The logistic regression OR for
      elevated CRP (>3 mg/L) and 95% CI were estimated for individual PUFAs and for
      total n-3 and n-6 PUFA intakes. Models were adjusted for sociodemographical,
      lifestyle, anthropometric, and dietary variables. Interactions with vitamin E
      intakes were also assessed. Inverse associations were observed between intakes of
      total n-3 PUFAs [alpha-linolenic acid (ALA; 18:3n-3), ALA + eicosapentaenoic acid
      (EPA; 20:5n-3), EPA + docosapentaenoic acid (DPA; 22:5n-3), DPA + docosahexaenoic
      acid (DHA; 22:6n-3)] and n-6 PUFA [linoleic acid (18:2n-6) + arachidonic acid
      (20:4n-6)] and elevated CRP (OR for tertile 3 vs. tertile 1 of intake: 0.41; 95%
      CI: 0.21, 0.77; P-trend = 0.01; and OR 0.38; 95% CI: 0.21, 0.70; P-trend = 0.002,
      respectively). Stratification on vitamin E intakes showed that inverse
      associations between dietary n-3 and n-6 PUFA intakes and elevated CRP were
      substantial only in individuals with low intakes of vitamin E. Our results
      supported the contention that intakes of both n-3 and n-6 PUFAs are inversely
      associated with plasma CRP concentrations. Vitamin E is a potential effect
      modifier and should therefore be taken into account in such investigations. This
      trial was registered at clinicaltrials.gov as NCT00272428. 

PMID- 24027185
TI  - Dietary patterns within a population are more reproducible than those of
      individuals.
AB  - Insight into the stability of dietary behavior over time is important, because
      only a single measurement of diet is often available to study the association
      between eating behavior and the occurrence of chronic diseases many years after
      baseline data collection. Little is known about changes in dietary patterns over
      time. The current study examined the (internal) stability and reproducibility of
      dietary patterns and the transition of individuals between patterns over time
      from 3 surveys within one study population by using cluster analysis. The dietary
      intake of participants in the Doetinchem Cohort Study in 6113, 4916, and 4520
      adults in 1993-1997, 1998-2002, and 2003-2007, respectively, was measured using a
      validated food-frequency questionnaire. Stability and reproducibility of dietary
      patterns were studied by examining the optimal number of clusters per survey by
      comparing the contribution of food groups to total energy intake within the
      clusters over time and by studying transitions of individuals between clusters
      over time. A low-fiber bread pattern and a high-fiber bread pattern were
      identified in all 3 surveys. Over time, dietary patterns were comparable in terms
      of foods contributing most to total energy intake, suggesting good
      reproducibility. Nevertheless, only 41.8% of the participants were consistently
      assigned to the same dietary pattern for all 3 surveys. This implies that, over
      time, similar dietary patterns were found at the group level, but that ignoring
      individual transitions between dietary patterns during follow-up may lead to
      misclassification of a large proportion of the study population. 

PMID- 24027186
TI  - Quality assurance issues in the use of dietary supplements, with special
      reference to protein supplements.
AB  - The use of dietary supplements is widespread in the general population, in
      athletes and recreational exercisers, and in military personnel. A wide array of
      supplements is available, but protein-containing products are consistently among
      the most popular, especially among those who engage in resistance training. There
      are significant risks associated with the use of unregulated dietary supplements.
      Risks include the absence of active ingredients, the presence of harmful
      substances (including microbiological agents and foreign objects), the presence
      of toxic agents, and the presence of potentially dangerous prescription-only
      pharmaceuticals. There is ample evidence of athletes who have failed doping tests
      because of the use of dietary supplements. There is also growing evidence of
      risks to health and of serious adverse events, including a small number of
      fatalities, as a result of supplement use. The risk associated with the use of
      protein powders produced by major manufacturers is probably low, and the risk can
      be further reduced by using only products that have been tested under one of the
      recognized supplement quality assurance programs that operate in various
      countries. Nevertheless, a small risk remains, and athletes, soldiers, and other
      consumers should conduct a cost-benefit analysis before using any dietary
      supplements. 

PMID- 24027189
TI  - Efficacy and safety of protein supplements for U.S. Armed Forces personnel:
      consensus statement.
AB  - To provide evidence-based guidance regarding the efficacy and safety of dietary
      protein supplement (PS) use by members of the U.S. Armed Forces, a panel of
      internationally recognized experts in the fields of protein metabolism and
      dietary supplement research was convened by the Department of Defense Center
      Alliance for Dietary Supplement Research and the U.S. Army Medical Research and
      Material Command. To develop a consensus statement, potential benefits, risks,
      and strategies to optimize military performance through PS use were considered in
      the context of specific warfighter populations and occupational demands. To
      maintain muscle mass, strength, and performance during periods of substantial
      metabolic demand and concomitant negative energy balance the panel recommended
      that warfighters consume 1.5-2.0 g . kg(-1) . d(-1) of protein. However, if
      metabolic demand is low, such as in garrison, protein intake should equal the
      current Military Dietary Reference Intake (0.8-1.5 g . kg(-1) . d(-1)). Although
      PS use generally appears to be safe for healthy adults, warfighters should be
      educated on PS quality, given quality-control and contamination concerns with
      commercial dietary supplements. To achieve recommended protein intakes, the panel
      strongly urges consumption of high-quality protein-containing whole foods.
      However, when impractical, the use of PSs (20-25 g per serving or 0.25-0.3 g .
      kg(-1) per meal), particularly after periods of strenuous physical activity
      (e.g., military training, combat patrols, and exercise), is acceptable. The
      committee acknowledges the need for further study of protein requirements for
      extreme, military-specific environmental conditions and whether unique metabolic
      stressors associated with military service alter protein requirements for aging
      warfighters. 

PMID- 24027187
TI  - The human milk metabolome reveals diverse oligosaccharide profiles.
AB  - Breast milk delivers nutrition and protection to the developing infant. There has
      been considerable research on the high-molecular-weight milk components; however,
      low-molecular-weight metabolites have received less attention. To determine the
      effect of maternal phenotype and diet on the human milk metabolome, milk
      collected at day 90 postpartum from 52 healthy women was analyzed by using proton
      nuclear magnetic resonance spectroscopy. Sixty-five milk metabolites were
      quantified (mono-, di-, and oligosaccharides; amino acids and derivatives; energy
      metabolites; fatty acids and associated metabolites; vitamins, nucleotides, and
      derivatives; and others). The biological variation, represented as the percentage
      CV of each metabolite, varied widely (4-120%), with several metabolites having
      low variation (<20%), including lactose, urea, glutamate, myo-inositol, and
      creatinine. Principal components analysis identified 2 clear groups of
      participants who were differentiable on the basis of milk oligosaccharide
      concentration and who were classified as secretors or nonsecretors of
      fucosyltransferase 2 (FUT2) gene products according to the concentration of 2'
      fucosyllactose, lactodifucotetraose, and lacto-N-fucopentaose I. Exploration of
      the interrelations between the milk sugars by using Spearman rank correlations
      revealed significant positive and negative associations, including positive
      correlations between fucose and products of the FUT2 gene and negative
      correlations between fucose and products of the fucosyltransferase 3 (FUT3) gene.
      The total concentration of milk oligosaccharides was conserved among participants
      (%CV = 18%), suggesting tight regulation of total oligosaccharide production;
      however, concentrations of specific oligosaccharides varied widely between
      participants (%CV = 30.4-84.3%). The variability in certain milk metabolites
      suggests possible roles in infant or infant gut microbial development. This trial
      was registered at clinicaltrials.gov as NCT01817127. 

PMID- 24027188
TI  - Increased protein intake in military special operations.
AB  - Special operations are so designated for the specialized military missions they
      address. As a result, special operations present some unique metabolic
      challenges. In particular, soldiers often operate in a negative energy balance in
      stressful and demanding conditions with little opportunity for rest or recovery.
      In this framework, findings inferred from the performance literature suggest that
      increased protein intake may be beneficial. In particular, increased protein
      intake during negative caloric balance maintains lean body mass and blood glucose
      production. The addition of protein to mixed macronutrient supplements is
      beneficial for muscle endurance and power endpoints, and the use of amino acids
      improves gross and fine motor skills. Increasing protein intake during periods of
      intense training and/or metabolic demand improves subsequent performance,
      improves muscular recovery, and reduces symptoms of psychological stress.
      Consumption of protein before sleep confers the anabolic responses required for
      the maintenance of lean mass and muscle recovery. A maximal response in muscle
      protein synthesis is achieved with the consumption of 20-25 g of protein alone.
      However, higher protein intakes in the context of mixed-nutrient ingestion also
      confer anabolic benefits by reducing protein breakdown. Restricted rations issued
      to special operators provide less than the RDA for protein ( ~ 0.6 g/kg), and
      these soldiers often rely on commercial products to augment their rations. The
      provision of reasonable alternatives and/or certification of approved supplements
      by the U.S. Department of Defense would be prudent. 

PMID- 24027190
TI  - Probing cytoskeletal structures by coupling optical superresolution and AFM
      techniques for a correlative approach.
AB  - In this article, we describe and show the application of some of the most
      advanced fluorescence superresolution techniques, STED AFM and STORM AFM
      microscopy towards imaging of cytoskeletal structures, such as microtubule
      filaments. Mechanical and structural properties can play a relevant role in the
      investigation of cytoskeletal structures of interest, such as microtubules, that
      provide support to the cell structure. In fact, the mechanical properties, such
      as the local stiffness and the elasticity, can be investigated by AFM force
      spectroscopy with tens of nanometers resolution. Force curves can be analyzed in
      order to obtain the local elasticity (and the Young's modulus calculation by
      fitting the force curves from every pixel of interest), and the combination with
      STED/STORM microscopy integrates the measurement with high specificity and yields
      superresolution structural information. This hybrid modality of superresolution
      AFM working is a clear example of correlative multimodal microscopy.

PMID- 24027191
TI  - A convenient alumination of functionalized aromatics by using the frustrated
      Lewis pair Et3 Al and TMPMgCl?LiCl.
AB  - A straightforward and efficient alumination of functionalized arenes by using the
      frustrated Lewis pair Et3 Al and TMPMgCl?LiCl (TMP=2,2,6,6-tetramethylpiperidyl)
      has been developed. In particular, halogenated electron-rich aromatics can be
      smoothly functionalized by using the frustrated Lewis pair Et3 Al and
      TMPMgCl?LiCl. Compared with previously described alumination methods, this
      procedure avoids extensive cooling and the need for an excess of base. This in
      situ procedure has proven to be most practical and allows for regio- and
      chemoselective metalation of a wide range of aromatics with sensitive functional
      groups (CONEt2 , CO2 Me, CN, OCONMe2 ) or halogens (F, Cl, Br, I). The resulting
      aromatic aluminates, which were characterized by using NMR spectroscopy, were
      subjected to allylations, acylations, and palladium-catalyzed cross-coupling
      reactions after transmetalation to zinc. It was shown that the nature of the Zn
      salt used for transmetalation is crucial. Thus, compared with ZnCl2 (2 equiv),
      the use of Zn(OPiv)2 (2 equiv; OPiv=pivalate) allows the subsequent quenching
      reactions to be performed with only a slight excess of electrophile (1.2 equiv)
      and provides interesting functionalized aromatics in good yields. 

PMID- 24027192
TI  - Real world navigation independence in the early blind correlates with
      differential brain activity associated with virtual navigation.
AB  - Navigating is a complex cognitive task that places high demands on spatial
      abilities, particularly in the absence of sight. Significant advances have been
      made in identifying the neural correlates associated with various aspects of this
      skill; however, how the brain is able to navigate in the absence of visual
      experience remains poorly understood. Furthermore, how neural network activity
      relates to the wide variability in navigational independence and skill in the
      blind population is also unknown. Using functional magnetic resonance imaging, we
      investigated the neural correlates of audio-based navigation within a large
      scale, indoor virtual environment in early profoundly blind participants with
      differing levels of spatial navigation independence (assessed by the Santa
      Barbara Sense of Direction scale). Performing path integration tasks in the
      virtual environment was associated with activation within areas of a core network
      implicated in navigation. Furthermore, we found a positive relationship between
      Santa Barbara Sense of Direction scores and activation within right temporal
      parietal junction during the planning and execution phases of the task. These
      findings suggest that differential navigational ability in the blind may be
      related to the utilization of different brain network structures. Further
      characterization of the factors that influence network activity may have
      important implications regarding how this skill is taught in the blind community.

PMID- 24027193
TI  - Are low maternal estriol levels a predictor for pro-opiomelanocortin (POMC)
      deficiency caused by POMC mutation during pregnancy?
AB  - Isolated adrenocorticotropic hormone deficiency is a rare cause of adrenocortical
      insufficiency, especially in children, and may be an underestimated cause of
      neonatal death. Low estriol levels are usually correlated with compromised
      uteroplacental perfusion and associated with fetal death. A 30-years old woman
      applied for pregnancy follow-up. Ultrasonographic evaluation and karyotype of the
      fetus are normal. Low estriol level 0.34 MoM (% 0.24) was detected in maternal
      triple screening test. Amniocentesis was performed, and chromosomal disorders,
      steroid sulfatase deficiency, and Smith-Lemli-Opitz syndrome (SLOS) were excluded
      with karyotype, fluorescence in situ hybridization (FISH), and molecular analysis
      of SLOS, respectively. As their first child had pro-opiomelanocortin (POMC)
      deficiency, POMC gene analysis was performed from both amniotic fluid and
      ethylene diamine tetra aceticacid (EDTA) blood sample of affected previous child,
      and homozygote mutation was detected. Fetus is diagnosed as POMC deficiency. We
      are presenting this case to discuss possible relationship of low maternal E3
      levels and fetal POMC deficiency.

PMID- 24027194
TI  - The validity of the distress thermometer in prostate cancer populations.
AB  - BACKGROUND: The Distress Thermometer (DT) is widely recommended for screening for
      distress after cancer. However, the validity of the DT in men with prostate
      cancer and over differing time points from diagnosis has not been well examined.
      METHOD: Receiver operating characteristics analyses were used to evaluate the
      diagnostic accuracy of the DT compared with three commonly used standardised
      scales in two prospective and one cross-sectional survey of men with prostate
      cancer (n = 740, 189 and 463, respectively). Comparison scales included the
      Impact of Event Scale - Revised (IES-R, Study 1), the Hospital Anxiety and
      Depression Scale (HADS, Study 2) and the Brief Symptom Inventory-18 (BSI-18,
      Study 3). RESULTS: Study 1: the DT showed good accuracy against the IES-R at all
      time points (area under curves (AUCs) ranging from 0.84 to 0.88) and sensitivity
      was high (>85%). Study 2: the DT performed well against both the anxiety and
      depression subscales for HADS at baseline (AUC = 0.84 and 0.82, respectively),
      but sensitivity decreased substantially after 12 months. Study 3: validity was
      high for the anxiety (AUC = 0.90, sensitivity = 90%) and depression (AUC = 0.85,
      sensitivity = 74%) subscales of the BSI-18 but was poorer for somatization (AUC =
      0.67, sensitivity = 52%). A DT cut-off between >=3 and >=6 maximised sensitivity
      and specificity across analyses. CONCLUSIONS: The DT is a valid tool to detect
      cancer-specific distress, anxiety and depression among prostate cancer patients,
      particularly close to diagnosis. A cut-off of >=4 may be optimal soon after
      diagnosis, and for longer-term assessments, >=3 was supported. (c) 2013 The
      Authors. Psycho-Oncology published by John Wiley & Sons, Ltd.

PMID- 24027195
TI  - Factor analysis of 27Al MAS NMR spectra for identifying nanocrystalline phases in
      amorphous geopolymers.
AB  - Nanostructured materials offer enhanced physicochemical properties because of the
      large interfacial area. Typically, geopolymers with specifically synthesized
      nanosized zeolites are a promising material for the sorption of pollutants. The
      structural characterization of these aluminosilicates, however, continues to be a
      challenge. To circumvent complications resulting from the amorphous character of
      the aluminosilicate matrix and from the low concentrations of nanosized
      crystallites, we have proposed a procedure based on factor analysis of (27)Al MAS
      NMR spectra. The capability of the proposed method was tested on geopolymers that
      exhibited various tendencies to crystallize (i) completely amorphous systems,
      (ii) X-ray amorphous systems with nanocrystalline phases, and (iii) highly
      crystalline systems. Although the recorded (27)Al MAS NMR spectra did not show
      visible differences between the amorphous systems (i) and the geopolymers with
      the nanocrystalline phase (ii), the applied factor analysis unambiguously
      distinguished these materials. The samples were separated into the well-defined
      clusters, and the systems with the evolving crystalline phase were identified
      even before any crystalline fraction was detected by X-ray powder diffraction.
      Reliability of the proposed procedure was verified by comparing it with (29)Si
      MAS NMR spectra. Factor analysis of (27)Al MAS NMR spectra thus has the ability
      to reveal spectroscopic features corresponding to the nanocrystalline phases.
      Because the measurement time of (27)Al MAS NMR spectra is significantly shorter
      than that of (29)Si MAS NMR data, the proposed procedure is particularly suitable
      for the analysis of large sets of specifically synthesized geopolymers in which
      the formation of the limited fractions of nanocrystalline phases is desired.

PMID- 24027196
TI  - Androgen receptor signaling regulates DNA repair in prostate cancers.
AB  - We demonstrate that the androgen receptor (AR) regulates a transcriptional
      program of DNA repair genes that promotes prostate cancer radioresistance,
      providing a potential mechanism by which androgen deprivation therapy synergizes
      with ionizing radiation. Using a model of castration-resistant prostate cancer,
      we show that second-generation antiandrogen therapy results in downregulation of
      DNA repair genes. Next, we demonstrate that primary prostate cancers display a
      significant spectrum of AR transcriptional output, which correlates with
      expression of a set of DNA repair genes. Using RNA-seq and ChIP-seq, we define
      which of these DNA repair genes are both induced by androgen and represent direct
      AR targets. We establish that prostate cancer cells treated with ionizing
      radiation plus androgen demonstrate enhanced DNA repair and decreased DNA damage
      and furthermore that antiandrogen treatment causes increased DNA damage and
      decreased clonogenic survival. Finally, we demonstrate that antiandrogen
      treatment results in decreased classical nonhomologous end-joining. SIGNIFICANCE:
      We demonstrate that the AR regulates a network of DNA repair genes, providing a
      potential mechanism by which androgen deprivation synergizes with radiotherapy
      for prostate cancer.

PMID- 24027198
TI  - Timely measles surveillance in the Republic of Korea, 2002-2009: impact of
      sentinel laboratory surveillance.
AB  - In order to sustain the elimination of measles, timely reporting is important.
      The surveillance data in Korea from 2002-2009 was analyzed to determine the
      effect of sentinel laboratory surveillance, which was introduced in 2006, on the
      timeliness of measles reporting. The data were stratified by two surveillance
      periods, (A) before and (B) after 2006, and by cases confirmed clinically and
      cases confirmed by laboratory measures. During Period A, 113 suspected cases were
      reported, and 241 during Period B. There was no difference in the proportion of
      timely reporting among cases confirmed clinically between the two periods,
      whereas the proportion of cases confirmed by laboratory measures has increased.
      The mean notification interval in cases confirmed by laboratory measures was
      shortened from 39 to 16 days. In Korea, sentinel laboratory surveillance has
      enhanced earlier detection of suspected cases that had not been reported,
      improving the timeliness of measles surveillance. Adopting this new method may
      improve the timely collection of cases in other countries.

PMID- 24027197
TI  - A hormone-DNA repair circuit governs the response to genotoxic insult.
AB  - Alterations in DNA repair promote tumor development, but the impact on tumor
      progression is poorly understood. Here, discovery of a biochemical circuit
      linking hormone signaling to DNA repair and therapeutic resistance is reported.
      Findings show that androgen receptor (AR) activity is induced by DNA damage and
      promotes expression and activation of a gene expression program governing DNA
      repair. Subsequent investigation revealed that activated AR promotes resolution
      of double-strand breaks and resistance to DNA damage both in vitro and in vivo.
      Mechanistically, DNA-dependent protein kinase catalytic subunit (DNAPKcs) was
      identified as a key target of AR after damage, controlling AR-mediated DNA repair
      and cell survival after genotoxic insult. Finally, DNAPKcs was shown to
      potentiate AR function, consistent with a dual role in both DNA repair and
      transcriptional regulation. Combined, these studies identify the AR-DNAPKcs
      circuit as a major effector of DNA repair and therapeutic resistance and
      establish a new node for therapeutic intervention in advanced disease.
      SIGNIFICANCE: The present study identifies for the fi rst time a positive
      feedback circuit linking hormone action to the DNA damage response and shows the
      significant impact of this process on tumor progression and therapeutic response.
      These provocative findings provide the foundation for development of novel nodes
      of therapeutic intervention for advanced disease.

PMID- 24027200
TI  - beta- and alpha-Hydride abstraction in Gold(I) alkyl complexes.
AB  - Why not both? Both beta- and alpha-hydrogen atoms of gold alkyl complexes are
      hydridic enough to be abstracted, opening a new route to gold-alkene and gold
      carbene complexes, respectively. 

PMID- 24027199
TI  - IL-9 and Th9 cells: progress and challenges.
AB  - T(h)9 cells are a new subset of helper T cells, and the signature cytokine for
      T(h)9 cells is IL-9. Both T(h)9 cells and T(h)9 products are implicated in
      multiple disease settings. Thus, a clear understanding of how T(h)9 cells are
      induced and controlled is an important and clinically relevant issue. There are
      different molecular pathways identified thus far in the induction of T(h)9 cells,
      and activation of such diverse pathways requires integration of signals from TGF
      beta and IL-4 cytokine receptors as well as costimulatory molecules. These
      signals converge on the induction of multiple transcription factors that
      collectively drive the development of T(h)9 cells.

PMID- 24027201
TI  - Controllable syntheses of porous metal-organic frameworks: encapsulation of
      Ln(III) cations for tunable luminescence and small drug molecules for efficient
      delivery.
AB  - Two porous metal-organic frameworks (MOFs), [Zn3 (L)(H2 O)2 ]?3 DMF?7 H2 O (MOF
      1) and [(CH3 )2 NH2 ]6 [Ni3 (L)2 (H2 O)6 ]?3 DMF?15 H2 O (MOF-2), were
      synthesized solvothermally (H6 L=1,2,3,4,5,6-hexakis(3
      carboxyphenyloxymethylene)benzene). In MOF-1, neighboring Zn(II) trimers are
      linked by the backbones of L ligands to form a fascinating 3D six-connected
      framework with the point symbol (4(12) .6(3) ) (4(12) .6(3) ). In MOF-2, eight L
      ligands bridge six Ni(II) atoms to generate a rhombic-dodecahedral [Ni6 L8 ]
      cage. Each cage is surrounded by eight adjacent ones through sharing of
      carboxylate groups to yield an unusual 3D porous framework. Encapsulation of
      Ln(III) cations for tunable luminescence and small drug molecules for efficient
      delivery were investigated in detail for MOF-1. 

PMID- 24027202
TI  - Looking for an ordinary life.

PMID- 24027203
TI  - A quantum question order model supported by empirical tests of an a priori and
      precise prediction.
AB  - Question order effects are commonly observed in self-report measures of judgment
      and attitude. This article develops a quantum question order model (the QQ model)
      to account for four types of question order effects observed in literature.
      First, the postulates of the QQ model are presented. Second, an a priori,
      parameter-free, and precise prediction, called the QQ equality, is derived from
      these mathematical principles, and six empirical data sets are used to test the
      prediction. Third, a new index is derived from the model to measure similarity
      between questions. Fourth, we show that in contrast to the QQ model, Bayesian and
      Markov models do not generally satisfy the QQ equality and thus cannot account
      for the reported empirical data that support this equality. Finally, we describe
      the conditions under which order effects are predicted to occur, and we review a
      broader range of findings that are encompassed by these very same quantum
      principles. We conclude that quantum probability theory, initially invented to
      explain order effects on measurements in physics, appears to be a powerful
      natural explanation for order effects of self-report measures in social and
      behavioral sciences, too. 

PMID- 24027204
TI  - Nanoscale topographic changes on sterilized glass surfaces affect cell adhesion
      and spreading.
AB  - Producing sterile glass surfaces is of great importance for a wide range of
      laboratory and medical applications, including in vitro cell culture and tissue
      engineering. However, sterilization may change the surface properties of glass
      and thereby affect its use for medical applications, for instance as a substrate
      for culturing cells. To investigate potential effects of sterilization on glass
      surface topography, borosilicate glass coverslips were left untreated or
      subjected to several common sterilization procedures, including low-temperature
      plasma gas, gamma irradiation and steam. Imaging by atomic force microscopy
      demonstrated that the surface of untreated borosilicate coverslips features a
      complex landscape of microislands ranging from 1000 to 3000 nm in diameter and 1
      to 3 nm in height. Steam treatment completely removes these microislands,
      producing a nanosmooth glass surface. In contrast, plasma treatment partially
      degrades the microisland structure, while gamma irradiation has no effect on
      microisland topography. To test for possible effects of the nanotopographic
      structures on cell adhesion, human gingival fibroblasts were seeded on untreated
      or sterilized glass surfaces. Analyzing fibroblast adhesion 3, 6, and 24 h after
      cell seeding revealed significant differences in cell attachment and spreading
      depending on the sterilization method applied. Furthermore, single-cell force
      spectroscopy revealed a connection between the nanotopographic landscape of glass
      and the formation of cellular adhesion forces, indicating that fibroblasts
      generally adhere weakly to nanosmooth but strongly to nanorough glass surfaces.
      Nanotopographic changes induced by different sterilization methods may therefore
      need to be considered when preparing sterile glass surfaces for cell culture or
      biomedical applications.

PMID- 24027205
TI  - Chinese men's knowledge and risk factors of osteoporosis: compared with women's.
AB  - Male osteoporosis is underappreciated. Little is known about men's knowledge of
      osteoporosis and how much men are at risk. This study surveyed men's knowledge of
      osteoporosis and their risk factors with reference to women in the primary care
      setting in Macau, China. A convenience sample of 302 men and 635 women aged 18 to
      90 years completed questionnaires comprising the Osteoporosis Knowledge
      Assessment Tool and the One-Minute Osteoporosis Risk Test. Their risks of
      osteoporosis were assessed with the Osteoporosis Self-Assessment Screening Test.
      Men and women, who were aged 55 years or below, had similarly limited knowledge
      of osteoporosis. People aged above 55 years had significantly less knowledge; men
      had less knowledge than women only in this age-group. If questions specific to
      women or menopause were excluded, men had similar knowledge as women. A higher
      proportion of men than women had risk factors as more men consumed alcohol or
      smoked tobacco. Similar proportions of men and women reported a loss of 1 inch in
      body height after age 40. After age 55, 29.2% men were at medium to high risk of
      osteoporosis. This study concludes that health education and primary prevention
      of osteoporosis should be promoted to men starting in middle-age. 

PMID- 24027206
TI  - Legalization of medical marijuana (Cannabis).

PMID- 24027207
TI  - Intrainsular functional connectivity in human.
AB  - OBJECTIVES: The anatomical organization of the insular cortex is characterized by
      its rich and heterogeneous cytoarchitecture and its wide network of connections.
      However, only limited knowledge is available regarding the intrainsular
      connections subserving the complex integrative role of the insular cortex. The
      aim of this study was to analyze the functional connectivity within- and across
      insular subregions, at both gyral and functional levels. EXPERIMENTAL DESIGN: We
      performed intracerebral electrical stimulation in 10 patients with refractory
      epilepsy investigated with depth electrodes, 38 of which were inserted in the
      insula. Bipolar electrical stimulation, consisting of two series of 20 pulses of
      1-ms duration, 0.2-Hz frequency, and 1-mA intensity, was delivered at each
      insular contact. For each stimulated insular anatomical region, we calculated a
      rate of connectivity, reflecting the proportion of other insular contacts,
      showing significant evoked potentials. RESULTS: Statistically significant evoked
      potentials were recorded in 74% of tested connections, with an average latency of
      26 +/- 3 ms. All insular gyri were interconnected, except the anterior and
      posterior short gyri. Most connections were reciprocal, showing no clear anterior
      to posterior directionality. No connection was observed between the right and the
      left insula. CONCLUSIONS: These findings point to specific features of human
      insula connectivity as compared to non-Human primates, and remain consistent with
      the complex integration role devoted to the human insula in many cognitive
      domains. Periodicals, Inc.

PMID- 24027208
TI  - Structural features and interfacial properties of WH2, beta-thymosin domains and
      other intrinsically disordered domains in the regulation of actin cytoskeleton
      dynamics.
AB  - Many actin-binding proteins (ABPs) use complex multidomain architectures to
      integrate and coordinate multiple signals and interactions with the dynamic
      remodeling of actin cytoskeleton. In these proteins, small segments that are
      intrinsically disordered in their unbound native state can be functionally as
      important as identifiable folded units. These functional intrinsically disordered
      regions (IDRs) are however difficult to identify and characterize in vitro. Here,
      we try to summarize the state of the art in understanding the structural features
      and interfacial properties of IDRs involved in actin self-assembly dynamics.
      Recent structural and functional insights into the regulation of widespread,
      multifunctional WH2/beta-thymosin domains, and of other IDRs such as those
      associated with WASP/WAVE, formin or capping proteins are examined. Understanding
      the functional versatility of IDRs in actin assembly requires apprehending by
      multiple structural and functional approaches their large conformational
      plasticity and dynamics in their interactions. In many modular ABPs, IDRs relay
      labile interactions with multiple partners and act as interaction hubs in
      interdomain and protein-protein interfaces. They thus control multiple
      conformational transitions between the inactive and active states or between
      various active states of multidomain ABPs, and play an important role to
      coordinate the high turnover of interactions in actin self-assembly dynamics.

PMID- 24027209
TI  - Influence of Bacillus spp. strains on seedling growth and physiological
      parameters of sorghum under moisture stress conditions.
AB  - Microorganisms isolated from stressed ecosystem may prove as ideal candidates for
      development of bio-inoculants for stressed agricultural production systems. In
      the present study, moisture stress tolerant rhizobacteria were isolated from the
      rhizosphere of sorghum, pigeonpea, and cowpea grown under semiarid conditions in
      India. Four isolates KB122, KB129, KB133, and KB142 from sorghum rhizosphere
      exhibited plant growth promoting traits and tolerance to salinity, high
      temperature, and moisture stress. These isolates were identified as Bacillus spp.
      by 16S rDNA sequence analysis. The strains were evaluated for growth promotion of
      sorghum seedlings under two different moisture stress conditions (set-I,
      continuous 50% soil water holding capacity (WHC) throughout the experiment and
      set-II, 75% soil WHC for 27 days followed by no irrigation for 5 days) under
      greenhouse conditions. Plate count and scanning electron microscope studies
      indicated successful root surface colonization by inoculated bacteria. Plants
      inoculated with Bacillus spp. strains showed better growth in terms of shoot
      length and root biomass with dark greenish leaves due to high chlorophyll content
      while un-inoculated plants showed rolling of the leaves, stunted appearance, and
      wilting under both stress conditions. Inoculation also improved leaf relative
      water content and soil moisture content. However, variation in proline and sugar
      content in the different treatments under two stress conditions indicated
      differential effect of microbial treatments on plant physiological parameters
      under stress conditions. 

PMID- 24027210
TI  - Tuning redox chemistry and photophysics in core-substituted tetraazaperopyrenes
      (TAPPs).
AB  - Core substitution of tetraazaperopyrenes (TAPPs) has been achieved, and with it,
      considerable variation of their photo- and redox-chemical properties. Through
      Suzuki cross coupling starting from the fourfold core-brominated
      tetraazaperopyrene, aryl-substituted TAPPs were synthesized, which displayed very
      high fluorescence quantum yields (up to 100 %) in solution. Besides the Suzuki
      reactions, Stille and Sonogashira cross-couplings were also found to be suitable
      methods for core derivatization, as demonstrated in the syntheses of alkynyl
      substituted tetraazaperopyrene congeners. Furthermore, TAPPs incorporating
      intramolecular donor-acceptor combinations of aromatic units (8, 9) were
      accessible by coupling the electron-poor peropyrene core with electron-rich
      aromatic units, which act as strong electron donors. Finally, C-heteroatom
      coupling (O, S, N) gave rise to novel TAPP derivatives with strongly modified
      redox-chemical behaviour and photophysics in the solid state as well in solution.
      In particular, TAPP derivatives displaying red fluorescence were obtained for the
      first time. 

PMID- 24027211
TI  - Health-related quality-of-life and psychological distress of young adult
      survivors of childhood cancer in Hong Kong.
AB  - BACKGROUND AND PURPOSE: Previous literatures on young adult survivors of
      childhood cancer show inconsistent findings with regards to their psychological
      distress and health-related quality of life (HRQOL). Much of the available data
      focus on negative patient outcomes following cancer treatments prescribed from
      1970 to 1990. In the present study, HRQOL and psychological distress of young
      adult survivors in Hong Kong was examined. It focused on subjects who had
      received cancer treatments prescribed in the last two decades. METHODS: A
      structured telephone survey was conducted with 614 eligible survivors and 208
      sibling controls in Hong Kong. RESULTS: The survivors reported significantly
      lower mean scores in physical role and functioning, whereas their mental, social,
      and psychological well-being was similar to that of their sibling controls. Being
      female, older age, longer survival time, and specific cancer diagnoses were the
      factors associated with poorer physical and mental adaptation. HRQOL was
      negatively correlated with psychological distress. CONCLUSIONS: Findings of the
      study suggest that most survivors adjusted fairly well in mental, psychological,
      and social aspects. Survivors with a higher risk of poor HRQOL could benefit from
      appropriate screening and counseling at an early stage to mitigate their
      survivorship difficulties. Prospective follow-up studies on childhood cancer
      survivors are recommended to detect changes over longer survival periods.

PMID- 24027212
TI  - HCSE method for detection of small carbon-carbon couplings and their signs,
      comparison with SLAP pulse sequence.
AB  - Performance of homonuclear coupling sign edited (HCSE) experiment applied to
      detection of signed carbon-carbon couplings is discussed using a set of already
      measured samples of nine monosubstituted benzenes. It is shown that coupling sign
      detection is insensitive to the settings of carbon-carbon polarization transfer
      delays. The HCSE spectra of ten from the total of 43 measured carbon-carbon
      couplings were considerably influenced by relaxations and proton-proton strong
      couplings. These effects are quantitatively discussed. The results of HCSE and
      SLAP experiments are compared. It is shown that the two methods may complement
      each other in detection of signed carbon-carbon couplings.

PMID- 24027214
TI  - Deferasirox induces mesenchymal-epithelial transition in crocidolite-induced
      mesothelial carcinogenesis in rats.
AB  - Asbestos was used worldwide in huge quantities in the past century. However,
      because of the unexpected carcinogenicity to mesothelial cells with an extremely
      long incubation period, many countries face this long-lasting social problem.
      Mesothelioma is often diagnosed in an advanced stage, for which no effective
      therapeutic protocols are yet established. We previously reported on the basis of
      animal experiments that the major pathology in asbestos-induced mesothelial
      carcinogenesis is local iron overload. Here, we undertook to find an effective
      strategy to prevent, delay, or lower the malignant potential of mesothelioma
      during asbestos-induced carcinogenesis. We used intraperitoneal injections of
      crocidolite to rats. We carried out a 16-week study to seek the maximal-tolerated
      intervention for iron reduction via oral deferasirox administration or intensive
      phlebotomy. Splenic iron deposition was significantly decreased with either
      method, and we found that Perls' iron staining in spleen is a good indicator for
      iron reduction. We injected a total of 10 mg crocidolite at the age of six weeks,
      and the preventive measures were via repeated oral administration of 25 to 50
      mg/kg/d deferasirox or weekly to bimonthly phlebotomy of 4 to 10 mL/kg/d. The
      animals were observed until 110 weeks. Deferasirox administration significantly
      increased the fraction of less malignant epithelioid subtype. Although we found a
      slightly prolonged survival in deferasirox-treated female rats, larger sample
      size and refinement of the current protocol are necessary to deduce the cancer
      preventive effects of deferasirox. Still, our results suggest deferasirox serves
      as a potential preventive strategy in people already exposed to asbestos via iron
      reduction.

PMID- 24027213
TI  - Soluble IL-2 receptor and beta-2 microglobulin as possible serologic markers of
      neurologic disease in HTLV-1 infection.
AB  - The human T-cell leukemia virus (HTLV-1) is the causative agent of a variety of
      neurologic diseases, including HTLV-1 Associated Myelopathy (HAM/TSP) and
      overactive bladder. Investigation of immune markers such as soluble interleukin-2
      receptor (sIL-2R) and beta-2 microglobulin (B2M) has shown some promising results
      in distinguishing patients with neurologic disease from those with carrier
      status. The objective of the present study was to determine if plasma levels of
      sIL-2R and B2M are markers of neurologic disease in individuals infected with
      HTLV-1. The present study was divided into two parts. A cross-sectional study and
      a nested case control study. In the cross-sectional study, HAM/TSP patients had
      higher plasma levels of B2M and sIL-2R than patients with overactive bladder and
      HTLV-1 carriers (P < 0.01 for all comparisons). For the nested case control
      study, the sIL-2 receptor test was able to distinguish patients with HAM/TSP from
      patients in the combined group of carriers and patients with overactive bladder
      with a sensitivity of 75.8% and false positive rate of 25.4%. Plasma levels of
      these markers did not change with the development of HAM/TSP and overactive
      bladder in HTLV-1 carrier patients. The present study has shown the importance of
      sIL-2 receptor in helping identifying HAM/TSP. However, the levels of these
      makers did not change significantly with the development of neurologic disease.

PMID- 24027216
TI  - Structural insights into incorporation of norbornene amino acids for click
      modification of proteins.
AB  - Three for two: by using a Methanosarcina mazei PylRS triple mutant (Y306G, Y384F,
      I405R) the incorporation of two new exo-norbornene-containing pyrrolysine
      analogues was achieved. X-ray crystallographic analysis led to the identification
      of the crucial structural elements involved in substrate recognition by the
      evolved synthetase.

PMID- 24027215
TI  - The potential of using quantum theory to build models of cognition.
AB  - Quantum cognition research applies abstract, mathematical principles of quantum
      theory to inquiries in cognitive science. It differs fundamentally from
      alternative speculations about quantum brain processes. This topic presents new
      developments within this research program. In the introduction to this topic, we
      try to answer three questions: Why apply quantum concepts to human cognition? How
      is quantum cognitive modeling different from traditional cognitive modeling? What
      cognitive processes have been modeled using a quantum account? In addition, a
      brief introduction to quantum probability theory and a concrete example is
      provided to illustrate how a quantum cognitive model can be developed to explain
      paradoxical empirical findings in psychological literature. 

PMID- 24027217
TI  - Zwitterionic base-stabilized digermadistannacyclobutadiene and
      tetragermacyclobutadiene.
AB  - The syntheses of a zwitterionic base-stabilized digermadistannacyclobutadiene and
      tetragermacyclobutadiene supported by amidinates and low-valent germanium
      amidinate substituents are described. The reaction of the amidinate Ge(I) dimer,
      [LGe:]2 (1, L=PhC(NtBu)2 ), with two equivalents of the amidinate tin(II)
      chloride, [LSnCl] (2), and KC8 in tetrahydrofuran (THF) at room temperature
      afforded a mixture of the zwitterionic base-stabilized
      digermadistannacyclobutadiene, [L2 Ge2 Sn2 L'2 ] (3; L'=LGe:), and the
      bis(amidinate) tin(II) compound, [L2 Sn:] (4). Compound 3 can also be prepared by
      the reaction of 1 with [L(Ar) SnCl] (5, L(Ar) =tBuC(NAr)2 , Ar=2,6-iPr2 C6 H3 )
      in THF at room temperature. Moreover, the reaction of 1 with the "onio
      substituent transfer" reagent [4-NMe2 -C5 H4 NSiMe3 ]OTf (8) in THF and 4-(N,N
      dimethylamino)pyridine (DMAP) at room temperature afforded a mixture of the
      zwitterionic base-stabilized tetragermacyclobutadiene, [L4 Ge6 ] (9), the
      amidinium triflate, [PhC(NHtBu)2 ]OTf (10), and Me3 SiSiMe3 (11). X-ray
      structural data and theoretical studies show conclusively that compounds 3 and 9
      have a planar and rhombic charge-separated structure. They are also nonaromatic. 

PMID- 24027219
TI  - Return to work with chronic pain: employers' and employees' views.
AB  - BACKGROUND: The sickness certification and return to work (RTW) of people with
      chronic pain are important health and economic issues for employees, employers,
      taxpayers and the UK government. The 'fit note' and a national educational
      programme promoting RTW were introduced in 2010 to curb rising rates of sickness
      absence. AIMS: To investigate employers' and employees' experiences of managing
      RTW when someone has taken sick leave for chronic pain and to explore the
      perceived efficacy of the fit note. METHODS: A qualitative study, comprising semi
      structured interviews with employers who had managed sick leave cases and
      employees who had experienced sick leave for chronic pain. Interviews were
      recorded, transcribed and the data analysed using constructivist grounded theory
      principles. RESULTS: Five themes were elicited. Firstly, frequent enquiry after
      health status was seen as intrusive by some employees but part of good practice
      by employers and acknowledging this difference was useful. Secondly, being able
      to trust employees due to their performance track record was helpful for
      employers when dealing with complex chronic pain conditions. Thirdly, feeling
      valued increased employees' motivation to RTW. Fourthly, guidelines about
      maintaining contact with absent employees were useful if used flexibly. Finally,
      both parties valued the fit note for its positive language, interrogative format
      and biomedical authority. CONCLUSIONS: The fit note was perceived to be helpful
      if used in combination with other strategies for managing sick leave and RTW for
      people with chronic pain. These strategies may be applicable to other
      fluctuating, long-term conditions with medically unexplained elements.

PMID- 24027218
TI  - Vitamin D status of Canadians employed in northern latitudes.
AB  - BACKGROUND: Vitamin D deficiency and insufficiency are prevalent worldwide, but
      relatively few studies have examined vitamin D status in working populations.
      AIMS: To assess the prevalence of vitamin D deficiency and insufficiency in
      Canadian workers and investigate risk factors in this population. METHODS: A
      cross-sectional study using data from a health programme enrolling workers mostly
      from Northern Alberta, Canada. As part of the programme, volunteers were invited
      to complete a lifestyle questionnaire. Blood was taken to determine plasma 25
      hydroxyvitamin D (25(OH)D) levels. Logistic and linear regressions were used to
      investigate the relationships between individual characteristics and vitamin D
      status. RESULTS: Between October 2007 and December 2012, 6101 eligible workers
      enrolled in the health programme. The prevalence of vitamin D deficiency (plasma
      25(OH)D, levels <27.5 nmol/l) and insufficiency (<37.5 nmol/l) were 3 and 8%,
      respectively. Male employees were significantly more likely to be vitamin D
      deficient and insufficient than females. Residing at a more northern latitude
      increased the likelihood of vitamin D deficiency and insufficiency. Age,
      assessments made in summer, better general health and physical activity and use
      of vitamin D supplementation were all related to lower likelihood of deficiency
      and insufficiency. CONCLUSIONS: Vitamin D deficiency and insufficiency are a
      concern in this sample of Canadian workers. Vitamin D supplementation is
      recommended to reduce the prevalence of deficiency and insufficiency in this
      group.

PMID- 24027220
TI  - Determination of a novel integron-located variant (blaOXA -320 ) of Class D beta
      lactamase in Proteus mirabilis.
AB  - Proteus mirabilis (P. mirabilis) is one of Gram-negative pathogens encountered in
      clinical specimens. A clinical isolate (TRP41) of P. mirabilis was isolated from
      a Turkish patient in Turkey. The isolate was identified using the API 32GN system
      and 16S rRNA gene sequencing and it was found resistant to ampicillin/sulbactam,
      piperacillin, tetracycline, and trimethoprim/sulfamethoxazole. This isolate was
      harboring a Class 1 integron gene cassette and its DNA sequence analysis revealed
      a novel blaOXA variant exhibiting one amino acid substitution (Asn266Ile) from
      blaOXA-1 . This new variant of OXA was located on Class 1 integron together with
      aadA1 gene encoding aminoglycoside-modifying enzymes. According to sequence
      records, the new variant was named as blaOXA-320 . Cassette array and size of
      integron were found as blaOXA-320 -aadA1 and 2086 bp, respectively. The blaOXA
      320 gene is not transferable according to conjugation experiment. In this study,
      we report the first identification of blaOXA-320 -aadA1 gene cassette, a novel
      variant of Class D beta-lactamase, in P. mirabilis from Turkey.

PMID- 24027221
TI  - Comorbid psychiatric disorders in female adolescents with first-onset anorexia
      nervosa.
AB  - OBJECTIVE: Patients with anorexia nervosa (AN) exhibit high rates of psychiatric
      comorbidity. To disentangle the effects of duration of illness on comorbid
      psychiatric symptoms, we investigated the rates of comorbid psychiatric
      disorders, suicidality and self-harm behaviour in adolescent patients with a
      first onset of AN. METHODS: In adolescent females (n = 148) with a first onset of
      AN, body mass index, psychiatric comorbidity (according to DSM-IV), depressive
      symptoms, suicidality and self-injurious behaviour were assessed. RESULTS:
      Seventy patients (47.3%) met the criteria for at least one comorbid psychiatric
      disorder. The binge-purging subtype was associated with increased rates of
      psychiatric comorbidity, suicidality and self-injurious behaviour. The severity
      of eating disorder-specific psychopathology influenced current psychiatric
      comorbidity and suicidal ideation. CONCLUSION: Prevalence rates of comorbid
      psychiatric disorders and suicidal ideation are considerably lower among
      adolescents with AN compared with adults. An early and careful assessment, along
      with adequate treatment of the eating disorder, might prevent the development of
      severe psychiatric comorbidities.

PMID- 24027222
TI  - Effects of borate-based bioactive glass on neuron viability and neurite
      extension.
AB  - Bioactive glasses have recently been shown to promote regeneration of soft
      tissues by positively influencing tissue remodeling during wound healing. We were
      interested to determine whether bioactive glasses have the potential for use in
      the treatment of peripheral nerve injury. In these experiments, degradable
      bioactive borate glass was fabricated into rods and microfibers. To study the
      compatibility with neurons, embryonic chick dorsal root ganglia (DRG) were
      cultured with different forms of bioactive borate glass. Cell viability was
      measured with no media exchange (static condition) or routine media exchange
      (transient condition). Neurite extension was measured within fibrin scaffolds
      with embedded glass microfibers or aligned rod sheets. Mixed cultures of neurons,
      glia, and fibroblasts growing in static conditions with glass rods and
      microfibers resulted in decreased cell viability. However, the percentage of
      neurons compared with all cell types increased by the end of the culture protocol
      compared with culture without glass. Furthermore, bioactive glass and fibrin
      composite scaffolds promoted neurite extension similar to that of control fibrin
      scaffolds, suggesting that glass does not have a significant detrimental effect
      on neuronal health. Aligned glass scaffolds guided neurite extension in an
      oriented manner. Together these findings suggest that bioactive glass can provide
      alignment to support directed axon growth.

PMID- 24027223
TI  - Multimodal use of new coumarin-based fluorescent chemosensors: towards highly
      selective optical sensors for Hg(2+) probing.
AB  - Despite several types of fluorescent sensing molecules have been proposed and
      examined to signal Hg(2+) ion binding, the development of fluorescence-based
      devices for in-field Hg(2+) detection and screening in environmental and
      industrial samples is still a challenging task. Herein, we report the synthesis
      and characterization of three new coumarin-based fluorescent chemosensors
      featuring mixed thia/aza macrocyclic framework as receptors units, that is,
      ligands L1-L3. These probes revealed an OFF-ON selective response to the presence
      of Hg(2+) ions in MeCN/H2 O 4:1 (v/v), which allowed imaging of this metal ion in
      Cos-7 cells in vitro. Once included in silica core-polyethylene glycol (PEG)
      shell nanoparticles or supported on polyvinyl chloride (PVC)-based polymeric
      membranes, ligands L1-L3 can also selectively sense Hg(2+) ions in pure water. In
      particular we have developed an optical sensing array tacking advantage of the
      fluorescent properties of ligand L3 and based on the computer screen photo
      assisted technique (CSPT). In the device ligand L3 is dispersed into PVC
      membranes and it quantitatively responds to Hg(2+) ions in natural water samples.

PMID- 24027224
TI  - The Necker-Zeno model for bistable perception.
AB  - A novel conceptual framework for theoretical psychology is presented and
      illustrated for the example of bistable perception. A basic formal feature of
      this framework is the non-commutativity of operations acting on mental states. A
      corresponding model for the bistable perception of ambiguous stimuli, the Necker
      Zeno model, is sketched and some empirical evidence for it so far is described.
      It is discussed how a temporal non-locality of mental states, predicted by the
      model, can be understood and tested. 

PMID- 24027225
TI  - Improved stereochemical analysis of conformationally flexible diamines by binding
      to a bisporphyrin molecular clip.
AB  - The relative stereochemistry of acyclic diamines with several stereogenic centers
      has been analyzed by NMR spectroscopy in combination with conformational
      deconvolution. Binding to a bisporphyrin molecular clip improves the
      stereochemical assignment significantly. The diamines were synthesized from
      inexpensive sugar alcohols, and their stable hydrochlorides were quantitatively
      converted into free bases by treatment with ion-exchange resin. 

PMID- 24027226
TI  - Unbiased tracking of the progression of mRNA and protein synthesis in bulk and in
      liposome-confined reactions.
AB  - The compartmentalization of a cell-free gene expression system inside a self
      assembled lipid vesicle is envisioned as the simplest chassis for the
      construction of a minimal cell. Although crucial for its realization,
      quantitative understanding of the dynamics of gene expression in bulk and
      liposome-confined reactions is scarce. Here, we used two orthogonal fluorescence
      labeling tools to report the amounts of mRNA and protein produced in a
      reconstituted biosynthesis system, simultaneously and in real-time. The Spinach
      RNA aptamer and its fluorogenic probe were used for mRNA detection. Applying this
      dual-reporter assay to the analysis of transcript and protein production inside
      lipid vesicles revealed that their levels are uncorrelated, most probably a
      consequence of the low copy-number of some components in liposome-confined
      reactions. We believe that the stochastic nature of gene expression should be
      appreciated as a design principle for the assembly of a minimal cell. 

PMID- 24027227
TI  - Effects of dopants on the biomechanical properties of conducting polymer films on
      platinum electrodes.
AB  - Conducting polymers have often been described in literature as a coating for
      metal electrodes which will dampen the mechanical mismatch with neural tissue,
      encouraging intimate cell interactions. However, there is very limited
      quantitative analysis of conducting polymer mechanics and the relation to tissue
      interactions. This article systematically analyses the impact of coating platinum
      (Pt) electrodes with the conducting polymer poly(ethylene dioxythiophene) (PEDOT)
      doped with a series of common anions which have been explored for neural
      interfacing applications. Nanoindentation was used to determine the coating
      modulus and it was found that the polymer stiffness increased as the size of the
      dopant ion was increased, with PEDOT doped with polystyrene sulfonate (PSS)
      having the highest modulus at 3.2 GPa. This was more than double that of the ClO4
      doped PEDOT at 1.3 GPa. Similarly, the electrical properties of these materials
      were shown to have a size dependent behavior with the smaller anions producing
      PEDOT films with the highest charge transfer capacity and lowest impedance.
      Coating stiffness was found to have a negligible effect on in vitro neural cell
      survival and differentiation, but rather polymer surface morphology, dopant
      toxicity and mobility is found to have the greatest impact.

PMID- 24027228
TI  - Biological and psychological predictors of visceral pain sensitivity in healthy
      premenopausal women.
AB  - BACKGROUND: Factors that are associated with pain perception remain incompletely
      understood, especially in the visceral pain field. Therefore, the current study
      aimed to investigate possible psychological and biological predictors of visceral
      pain sensitivity in healthy subjects. METHODS: In a sample of 59 healthy
      premenopausal female subjects on hormonal contraceptives, measures of
      gastrointestinal (GI) symptoms in daily life, trait and state anxiety,
      depression, serum cortisol concentrations and serum levels of interleukin-6 (IL
      6) were obtained, followed by assessment of rectal distension pain sensitivity
      measures (i.e., rectal distension sensory threshold, pain threshold and pain
      ratings for discrete rectal distension stimuli). RESULTS: Regression analyses
      showed that more GI symptoms in daily life predicted a lower pain threshold.
      Higher levels of state anxiety predicted a lower pain threshold. Higher cortisol
      concentrations predicted lower pain ratings. IL-6 was positively related to GI
      symptoms but was a non-significant predictor of pain threshold in the multiple
      regression analysis. CONCLUSIONS: Similar to findings in patients with functional
      GI symptoms, we showed that subclinical GI symptoms predict visceral pain
      sensitivity. In line with somatic pain findings, state but not trait anxiety was
      found to predict visceral pain sensitivity. Our finding on serum cortisol as
      positive predictor of pain sensitivity might be interpreted in light of
      immunosuppressive effects of cortisol. Our finding on the role of IL-6 in GI
      symptoms is promising for understanding GI complaints in patients and needs
      further investigation.

PMID- 24027229
TI  - Electronic tuning of iron-oxo-mediated C-H activation: effect of electron
      donating ligand on selectivity.
AB  - We have reported previously that an iron(III) complex supported by an anionic
      pentadentate monoamido ligand, dpaq(H) (dpaq(H) =2-[bis(pyridin-2-ylmethyl)]amino
      N-quinolin-8-yl-acetamido), promotes selective C?H hydroxylation with H2 O2 with
      high regioselectivity. Herein, we report on the preparation of Fe(III) -dpaq
      derivatives that have a series of substituent groups at the 5-position of a
      quinoline moiety in the parent ligand dpaq(H) (dpaq(R) , R: OMe, H, Cl, and NO2
      ), and examine them with respect to their catalytic activity in C?H hydroxylation
      with H2 O2 . As the substituent group becomes more electron-withdrawing, both the
      selectivity and the turnover number increase, but the selectivity of epoxidation
      shows the opposite trend. 

PMID- 24027230
TI  - Pediatric residents' perceptions of family-centered rounds as part of
      postgraduate training.
AB  - PURPOSE: Although family-centered rounds (FCRs) are recommended as standard
      practice, limited data address pediatric residents' opinions of FCRs. In the
      present study, we assessed residents' perceptions with respect to rounding
      experience and postgraduate year (PGY). METHODS: An anonymous online
      questionnaire was distributed to pediatric residents from nine accredited
      programs in New Jersey. RESULTS: Of 95 residents who completed questionnaires,
      69.5% participated in FCRs and traditional rounds, 17.9% in FCRs, and 12.6% in
      traditional rounds. Irrespective of rounding experience and PGY, the majority
      believed that FCRs benefit families and pediatric training, felt that an
      attending's style greatly affects their experience, report discomfort sharing
      sensitive information and answering questions, and did not support the
      superiority of FCRs for efficiency and professional satisfaction. CONCLUSIONS:
      Concerns regarding discomfort, attending approach and efficiency are potential
      barriers to residents' full acceptance of FCRs that should be addressed to
      improve the efficacy of postgraduate pediatric training.

PMID- 24027232
TI  - A 16-week-old infant with failure to thrive and hypotonia.

PMID- 24027233
TI  - A review of the use of clonidine as a sleep aid in the child and adolescent
      population.

PMID- 24027234
TI  - New anthracene derivatives as triplet acceptors for efficient green-to-blue low
      power upconversion.
AB  - Three new anthracene derivatives [2-chloro-9,10-dip-tolylanthracene (DTACl), 9,10
      dip-tolylanthracene-2-carbonitrile (DTACN), and 9,10-di(naphthalen-1
      yl)anthracene-2-carbonitrile (DNACN)] were synthesized as triplet acceptors for
      low-power upconversion. Their linear absorption, single-photon-excited
      fluorescence, and upconversion fluorescence properties were studied. The
      acceptors exhibit high fluorescence yields in DMF. Selective excitation of the
      sensitizer Pd(II)octaethylporphyrin (PdOEP) in solution containing DTACl, DTACN,
      or DNA-CN at 532 nm with an ultralow excitation power density of 0.5 W cm(-2)
      results in anti-Stokes blue emission. The maximum upconversion quantum yield
      (Phi(UC) =17.4%) was obtained for the couple PdOEP/DTACl. In addition, the
      efficiency of the triplet-triplet energy transfer process was quantitatively
      studied by quenching experiments. Experimental results revealed that a highly
      effective acceptor for upconversion should combine high fluorescence quantum
      yields with efficient quenching of the sensitizer triplet.

PMID- 24027231
TI  - Racial, ethnic, and language disparities in early childhood
      developmental/behavioral evaluations: a narrative review.

PMID- 24027235
TI  - Oxygen diffusion and consumption in extracellular matrix gels: implications for
      designing three-dimensional cultures.
AB  - Three-dimensional (3D) cultures are increasingly used as tissue surrogates to
      study many physiopathological processes. However, to what extent current 3D
      culture protocols provide physiologic oxygen tension conditions remains ill
      defined. To address this limitation, oxygen tension was measured in a panel of
      acellular or cellularized extracellular matrix (ECM) gels with A549 cells, and
      analyzed in terms of oxygen diffusion and consumption. Gels included
      reconstituted basement membrane, fibrin and collagen. Oxygen diffusivity in
      acellular gels was up to 40% smaller than that of water, and the lower values
      were observed in the denser gels. In 3D cultures, physiologic oxygen tension was
      achieved after 2 days in dense (>=3 mg/mL) but not sparse gels, revealing that
      the latter gels are not suitable tissue surrogates in terms of oxygen
      distribution. In dense gels, we observed a dominant effect of ECM composition
      over density in oxygen consumption. All diffusion and consumption data were used
      in a simple model to estimate ranges for gel thickness, seeding density and time
      window that may support physiologic oxygen tension. Thus, we identified critical
      variables for oxygen tension in ECM gels, and introduced a model to assess
      initial values of these variables, which may short-cut the optimization step of
      3D culture studies.

PMID- 24027236
TI  - Gold(I) and gold(III) trifluoromethyl derivatives.
AB  - Trifluoromethylation of AuCl3 by using the Me3 SiCF3 /CsF system in THF and in
      the presence of [PPh4 ]Br proceeds with partial reduction, yielding a mixture of
      [PPh4 ][Au(I) (CF3 )2 ] (1') and [PPh4 ][Au(III) (CF3 )4 ] (2') that can be
      adequately separated. An efficient method for the high-yield synthesis of 1' is
      also described. The molecular geometries of the homoleptic anions [Au(I) (CF3 )2
      ](-) and [Au(III) (CF3 )4 ](-) in their salts 1' and [NBu4 ][Au(III) (CF3 )4 ]
      (2) have been established by X-ray diffraction methods. Compound 1' oxidatively
      adds halogens, X2 , furnishing [PPh4 ][Au(III) (CF3 )2 X2 ] (X=Cl (3), Br (4), I
      (5)), which are assigned a trans stereochemistry. Attempts to activate C?F bonds
      in the gold(III) derivative 2' by reaction with Lewis acids under different
      conditions either failed or only gave complex mixtures. On the other hand,
      treatment of the gold(I) derivative 1' with BF3 ?OEt2 under mild conditions
      cleanly afforded the carbonyl derivative [Au(I) (CF3 )(CO)] (6), which can be
      isolated as an extremely moisture-sensitive light yellow crystalline solid. In
      the solid state, each linear F3 C-Au-CO molecule weakly interacts with three
      symmetry-related neighbors yielding an extended 3D network of aurophilic
      interactions (Au???Au=345.9(1) pm). The high $?tilde ?nu $CO value (2194 cm(-1)
      in the solid state and 2180 cm(-1) in CH2 Cl2 solution) denotes that CO is acting
      as a mainly sigma-donor ligand and confirms the role of the CF3 group as an
      electron-withdrawing ligand in organometallic chemistry. Compound 6 can be
      considered as a convenient synthon of the "Au(I) (CF3 )" fragment, as it reacts
      with a number of neutral ligands L, giving rise to the corresponding [Au(I) (CF3
      )(L)] compounds (L=CNtBu (7), NCMe (8), py (9), tht (10)). 

PMID- 24027237
TI  - Developmental inter-relations between early maternal depression, contextual
      risks, and interpersonal stress, and their effect on later child cognitive
      functioning.
AB  - BACKGROUND: Maternal depression and contextual risks (e.g. poverty) are known to
      impact children's cognitive and social functioning. However, few published
      studies have examined how stress in the social environment (i.e. interpersonal
      stress) might developmentally inter-relate with maternal depression and
      contextual risks to negatively affect a child in these domains. This was the
      purpose of the current study. METHOD: Mother-child pairs (n = 6979) from the Avon
      Longitudinal Study of Parents were the study participants. Mothers reported on
      depression, contextual risks, and interpersonal stress between pregnancy and 33
      months child age. At age 8, the children underwent cognitive assessments and the
      mothers reported on the children's social cognitive skills. RESULTS: Maternal
      depression, contextual risks, and interpersonal stress showed strong continuity
      and developmental inter-relatedness. Maternal depression and contextual risks
      directly predicted a range of child outcomes, including executive functions and
      social cognitive skills. Interpersonal stress worked indirectly via maternal
      depression and contextual risks to negatively affect child outcomes. CONCLUSION:
      Maternal depression and contextual risks each increased interpersonal stress in
      the household, which, in turn, contributed to reduced child cognitive and social
      functioning.

PMID- 24027238
TI  - Reactivity of fluoro-substituted bis(thiocarbonyl) donors with diiodine: an XRD,
      FT-Raman, and DFT investigation.
AB  - The reactions of 1,3,8,10-tetrakis(4'-fluorophenyl)-4,5,6,7-tetrathiocino[1,2
      b:3,4-b']diimidazolyl-2,9-dithione (4) and molecular diiodine afforded spoke
      adducts with stoichiometries 4.I2 and 4.3I2 , isolated in the compound
      4.3I2.xCH2Cl2.(1-x)I2 (x=0.70), and characterized by single-crystal XRD and FT
      Raman spectroscopy. The nature of the reaction products was investigated under
      the prism of theoretical calculations carried out at the DFT level. The
      structural data, FT-Raman spectroscopy, and quantum mechanical calculations agree
      in indicating that the introduction of fluorophenyl substituents results in a
      lowering of the Lewis basicity of this class of bis(thiocarbonyl) donors compared
      with alkyl-substituted tetrathiocino donors and fluorine allows for extended
      interactions that are responsible for solid-state crystal packing.

PMID- 24027239
TI  - Discrepancies between explicit and implicit self-esteem and their relationship to
      symptoms of depression and mania.
AB  - OBJECTIVES: Self-esteem is a key feature of bipolar symptomatology. However, so
      far no study has examined the interaction between explicit and implicit self
      esteem in individuals vulnerable to bipolar disorder. DESIGN: Cross-sectional
      design was employed. METHODS: Thirty children of parents with bipolar disorder
      and 30 offspring of control parents completed Hamilton Rating Scale for
      Depression, the Bech-Rafaelson Mania Scale, the Self-esteem Rating Scale and the
      Implicit Association Test. RESULTS: No differences between groups were revealed
      in levels of explicit or implicit self-esteem. However, bipolar offspring showed
      increased levels of symptoms of depression and mania. Furthermore, depressive
      symptoms were associated with low explicit self-esteem, whilst symptoms of mania
      were associated with low implicit self-esteem. When self-esteem discrepancies
      were examined, damaged self-esteem (i.e., low explicit but high implicit self
      esteem) was associated with depression, whilst no associations between mania and
      self-esteem discrepancies were found. CONCLUSIONS: Not only explicit, but also
      implicit self-esteem, and the interactions between the two are of relevance in
      bipolar symptoms. Clinical implications and future research directions are
      discussed. PRACTITIONER POINTS: Explicit as well as implicit SE, and particularly
      their relationship, are relevant for mental health. Fluctuations in implicit SE
      may serve as an early indicator for risk of bipolarity. Psychotherapeutic
      approaches may be more suitable for one kind of SE challenge than the other.

PMID- 24027240
TI  - Distinct functional properties of isoamylase-type starch debranching enzymes in
      monocot and dicot leaves.
AB  - Isoamylase-type starch debranching enzymes (ISA) play important roles in starch
      biosynthesis in chloroplast-containing organisms, as shown by the strict
      conservation of both catalytically active ISA1 and the noncatalytic homolog ISA2.
      Functional distinctions exist between species, although they are not understood
      yet. Numerous plant tissues require both ISA1 and ISA2 for normal starch
      biosynthesis, whereas monocot endosperm and leaf exhibit nearly normal starch
      metabolism without ISA2. This study took in vivo and in vitro approaches to
      determine whether organism-specific physiology or evolutionary divergence between
      monocots and dicots is responsible for distinctions in ISA function. Maize (Zea
      mays) ISA1 was expressed in Arabidopsis (Arabidopsis thaliana) lacking endogenous
      ISA1 or lacking both native ISA1 and ISA2. The maize protein functioned in
      Arabidopsis leaves to support nearly normal starch metabolism in the absence of
      any native ISA1 or ISA2. Analysis of recombinant enzymes showed that Arabidopsis
      ISA1 requires ISA2 as a partner for enzymatic function, whereas maize ISA1 was
      active by itself. The electrophoretic mobility of recombinant and native maize
      ISA differed, suggestive of posttranslational modifications in vivo.
      Sedimentation equilibrium measurements showed recombinant maize ISA1 to be a
      dimer, in contrast to previous gel permeation data that estimated the molecular
      mass as a tetramer. These data demonstrate that evolutionary divergence between
      monocots and dicots is responsible for the distinctions in ISA1 function. 

PMID- 24027241
TI  - Natural variation in the ATPS1 isoform of ATP sulfurylase contributes to the
      control of sulfate levels in Arabidopsis.
AB  - Sulfur is an essential macronutrient for all living organisms. Plants take up
      inorganic sulfate from the soil, reduce it, and assimilate it into bioorganic
      compounds, but part of this sulfate is stored in the vacuoles. In our first
      attempt to identify genes involved in the control of sulfate content in the
      leaves, we reported that a quantitative trait locus (QTL) for sulfate content in
      Arabidopsis (Arabidopsis thaliana) was underlain by the APR2 isoform of the key
      enzyme of sulfate assimilation, adenosine 5'-phosphosulfate reductase. To
      increase the knowledge of the control of this trait, we cloned a second QTL from
      the same analysis. Surprisingly, the gene underlying this QTL encodes the ATPS1
      isoform of the enzyme ATP sulfurylase, which precedes adenosine 5'-phosphosulfate
      reductase in the sulfate assimilation pathway. Plants with the Bay allele of
      ATPS1 accumulate lower steady-state levels of ATPS1 transcript than those with
      the Sha allele, which leads to lower enzyme activity and, ultimately, the
      accumulation of sulfate. Our results show that the transcript variation is
      controlled in cis. Examination of ATPS1 sequences of Bay-0 and Shahdara
      identified two deletions in the first intron and immediately downstream the gene
      in Bay-0 shared with multiple other Arabidopsis accessions. The average ATPS1
      transcript levels are lower in these accessions than in those without the
      deletions, while sulfate levels are significantly higher. Thus, sulfate content
      in Arabidopsis is controlled by two genes encoding subsequent enzymes in the
      sulfate assimilation pathway but using different mechanisms, variation in amino
      acid sequence and variation in expression levels. 

PMID- 24027243
TI  - Cell- and stimulus type-specific intracellular free Ca2+ signals in Arabidopsis.
AB  - Appropriate stimulus-response coupling requires that each signal induces a
      characteristic response, distinct from that induced by other signals, and that
      there is the potential for individual signals to initiate different downstream
      responses dependent on cell type. How such specificity is encoded in plant
      signaling is not known. One possibility is that information is encoded in signal
      transduction pathways to ensure stimulus- and cell type-specific responses. The
      calcium ion acts as a second messenger in response to mechanical stimulation,
      hydrogen peroxide, NaCl, and cold in plants and also in circadian timing. We use
      GAL4 transactivation of aequorin in enhancer trap lines of Arabidopsis
      (Arabidopsis thaliana) to test the hypothesis that stimulus- and cell-specific
      information can be encoded in the pattern of dynamic alterations in the
      concentration of intracellular free Ca(2+) ([Ca(2+)]i). We demonstrate that
      mechanically induced increases in [Ca(2+)]i are largely restricted to the
      epidermal pavement cells of leaves, that NaCl induces oscillatory [Ca(2+)]i
      signals in spongy mesophyll and vascular bundle cells, but not other cell types,
      and detect circadian rhythms of [Ca(2+)]i only in the spongy mesophyll. We
      demonstrate stimulus-specific [Ca(2+)]i dynamics in response to touch, cold, and
      hydrogen peroxide, which in the case of the latter two signals are common to all
      cell types tested. GAL4 transactivation of aequorin in specific leaf cell types
      has allowed us to bypass the technical limitations associated with fluorescent
      Ca(2+) reporter dyes in chlorophyll-containing tissues to identify the cell- and
      stimulus-specific complexity of [Ca(2+)]i dynamics in leaves of Arabidopsis and
      to determine from which tissues stress- and circadian-regulated [Ca(2+)]i signals
      arise. 

PMID- 24027244
TI  - Andrographolide: solving chemical instability and poor solubility by means of
      cocrystals.
AB  - The bioactive agent andrographolide was screened with pharmaceutically acceptable
      coformers to discover a novel solid form that will solve the chemical instability
      and poor solubility problems of this herbal medicine. Liquid-assisted grinding of
      andrographolide with GRAS (generally regarded as safe) coformers in a fixed
      stoichiometry resulted in cocrystals with vanillin (1:1), vanillic acid (1:1),
      salicylic acid (1:1), resorcinol (1:1), and guaiacol (1:1). All the crystalline
      products were characterized by thermal, spectroscopic, and diffraction methods.
      Interestingly, even though the cocrystals are isostructural, their
      physicochemical properties are quite different. The andrographolide-salicylic
      acid cocrystal completely inhibited the chemical transformation of
      andrographolide to its inactive sulfate metabolite, and moreover, the cocrystal
      exhibited a dissolution rate that was three times faster and a drug release that
      was two times higher than pure andrographolide. 

PMID- 24027242
TI  - The Arabidopsis cyclic nucleotide-gated ion channels AtCNGC2 and AtCNGC4 work in
      the same signaling pathway to regulate pathogen defense and floral transition.
AB  - Arabidopsis (Arabidopsis thaliana) cyclic nucleotide-gated ion channels (CNGCs)
      form a large family consisting of 20 members and have been implicated in Ca(2+)
      signaling related to various physiological processes, such as pathogen defense,
      development, and thermotolerance. The null mutant of AtCNGC2, defense, no death
      (dnd1), exhibits autoimmune phenotypes, while it is impaired in mounting the
      hypersensitive response, which is a hallmark of effector-triggered (i.e.
      RESISTANCE-gene mediated) resistance. It has been suggested that AtCNGC2 is
      involved in defense responses and likely other aspects of physiology through its
      role as a Ca(2+)-conducting channel. However, the downstream signaling components
      and its relation with AtCNGC4, which is the closest paralog of AtCNGC2, remain
      elusive. Despite the fact that cngc4 mutants display almost identical phenotypes
      to those seen in cngc2 mutants, not much is known about their relationship. Here,
      we report the identification and characterization of the Arabidopsis mutant
      repressor of defense no death1 (rdd1), obtained from a suppressor screen of a
      transfer DNA insertion knockout mutant of AtCNGC2 in order to identify downstream
      components of dnd1-mediated signal transduction. rdd1 suppressed the majority of
      dnd1-mediated phenotypes except Ca(2+) hypersensitivity. In addition, rdd1 also
      suppressed the dnd1-mediated late-flowering phenotype that was discovered in this
      study. Our genetic analysis conducted to elucidate the relationship between
      AtCNGC2 and AtCNGC4 indicates that RDD1 is also involved in AtCNGC4-mediated
      signal transduction. Lastly, bimolecular fluorescence complementation analysis
      suggests that AtCNGC2 and AtCNGC4 are likely part of the same channel complex. 

PMID- 24027246
TI  - N-heterocyclic-carbene-catalyzed one-pot synthesis of hydroxamic esters.

PMID- 24027245
TI  - Functional role of oligomerization for bacterial and plant SWEET sugar
      transporter family.
AB  - Eukaryotic sugar transporters of the MFS and SWEET superfamilies consist of 12
      and 7 alpha-helical transmembrane domains (TMs), respectively. Structural
      analyses indicate that MFS transporters evolved from a series of tandem
      duplications of an ancestral 3-TM unit. SWEETs are heptahelical proteins carrying
      a tandem repeat of 3-TM separated by a single TM. Here, we show that prokaryotes
      have ancestral SWEET homologs with only 3-TM and that the Bradyrhizobium
      japonicum SemiSWEET1, like Arabidopsis SWEET11, mediates sucrose transport.
      Eukaryotic SWEETs most likely evolved by internal duplication of the 3-TM,
      suggesting that SemiSWEETs form oligomers to create a functional pore. However,
      it remains elusive whether the 7-TM SWEETs are the functional unit or require
      oligomerization to form a pore sufficiently large to allow for sucrose passage.
      Split ubiquitin yeast two-hybrid and split GFP assays indicate that Arabidopsis
      SWEETs homo- and heterooligomerize. We examined mutant SWEET variants for
      negative dominance to test if oligomerization is necessary for function. Mutation
      of the conserved Y57 or G58 in SWEET1 led to loss of activity. Coexpression of
      the defective mutants with functional A. thaliana SWEET1 inhibited glucose
      transport, indicating that homooligomerization is necessary for function.
      Collectively, these data imply that the basic unit of SWEETs, similar to MFS
      sugar transporters, is a 3-TM unit and that a functional transporter contains at
      least four such domains. We hypothesize that the functional unit of the SWEET
      family of transporters possesses a structure resembling the 12-TM MFS structure,
      however, with a parallel orientation of the 3-TM unit. 

PMID- 24027247
TI  - Antimicrobial stewardship: English Surveillance Programme for Antimicrobial
      Utilization and Resistance (ESPAUR).
AB  - The clinical, public health and economic implications of antimicrobial resistance
      present a major threat to future healthcare. Antimicrobial use is a major driver
      of resistance, and antimicrobial stewardship programmes are increasingly being
      advocated as a means of improving the quality of prescribing. However, to
      increase their impact and assess their success, a better understanding of
      antimicrobial usage, both in primary and secondary care, and linkage with
      antimicrobial resistance data are required. In England, national summaries of
      primary care dispensing data are issued annually by the Health and Social Care
      Information Centre. However, there is currently no routine public reporting of
      antimicrobial usage in hospitals. In response to the threat posed by
      antimicrobial resistance, as highlighted in the Report of the Chief Medical
      Officer and on the request of the Department of Health, Public Health England has
      developed a new national programme, the English Surveillance Programme for
      Antimicrobial Utilization and Resistance (ESPAUR). The programme will bring
      together the elements of antimicrobial utilization and resistance surveillance in
      both primary and secondary care settings, alongside the development of quality
      measures and methods to monitor unintended outcomes of antimicrobial stewardship
      and both public and professional behaviour interventions. This article reports on
      the background to the programme development, the current oversight group
      membership and the public reporting structure. 

PMID- 24027250
TI  - A young 20-year-old woman with an atypical tuberculin reaction.
AB  - A 20-year-old female patient presented with fever and swelling in the neck
      accompanied by anorexia and weight loss. The clinical examination revealed a
      febrile patient with diffuse cervical lymphadenopathy. Routine investigations
      were negative. A 5TU (tuberculin units) tuberculin skin test (Mantoux test) was
      positive with an induration of 52 * 40 mm after 72 h with central blistering,
      exudation and ulceration. Aspiration cytology from the cervical lymph node
      revealed the presence of caseating granulomas. The patient responded completely
      to antitubrecular therapy. Enhanced-tuberculin reactions may occur on occasion in
      tuberculosis.

PMID- 24027249
TI  - Simultaneous bilateral spontaneous pneumothoraces: a case of occupational asthma.
AB  - Simultaneous bilateral spontaneous pneumothoraces (SBSP) are uncommon. This
      report presents the case of a previously well 19-year-old man with a diagnosis of
      SBSP and symptoms suggestive of occupational asthma. Despite bilateral bullectomy
      and pleurodesis using a video-assisted thoracoscopic surgical technique, the
      pneumothorax reoccurred unilaterally and open surgery was performed. This case
      illustrates a rare condition of bilateral pneumothoraces presenting as a first
      presentation of occupational asthma and the issues surrounding its management.

PMID- 24027251
TI  - A variation of vasculopathies in a patient with mild pulmonary artery
      hypertension.

PMID- 24027252
TI  - Renal aspergillosis secondary to renal intrumentation in immunocompetent patient.
AB  - Primary renal aspergillosis is a rare urological entity and immune-compromised
      persons are commonly prone to it. The clinical presentation resembles that of
      usual bacterial pyelonephritis. We report a case of localised unilateral renal
      aspergillosis with obstructive uropathy (hypoplastic contralateral kidney) in a
      young man, occurring after the endoscopic removal of impacted right upper
      ureteric calculus in a non-immunocompromised patient. In view of deranged renal
      function, he was initially managed by percutaneous nephrostomy and DJ stent
      removal followed by oral voriconazole therapy for 3 weeks. He responded well to
      the treatment. Subsequently, the patient was free of renal colic, fever and urine
      culture negative for Aspergillus.

PMID- 24027253
TI  - An important complication of a child with juvenile idiopathic arthritis:
      macrophage activation syndrome.
AB  - A 4-year-old girl, a known case of juvenile idiopathic arthritis for 2 years
      presented to us with high-grade fever and abdominal distension for 2 months. On
      examination, her temperature was 104  degrees  F and she was found to be pale
      with bilateral cervical lymphadenopathy of up to 3 * 3 cm in size. Her liver was
      enlarged with a firm consistency and a span of 12 cm. Her spleen was enlarged up
      to 3 cm along its long axis. The rest of her systemic examination was normal.
      Laboratory investigations revealed leucocytosis, anaemia and thrombocytopenia
      with a mildly elevated erythrocyte sedimentation rate. Serum ferritin was 16 500
      ng/dL and lactate dehydrogenase was 2311 U/L. A bone marrow aspirate showed
      macrophages showing ingested nuclei. She was diagnosed as having macrophage
      activation syndrome and was initiated on intravenous methylprednisolone 300 mg
      daily for 3 days and was switched over to oral prednisolone 2 mg/kg/day. She is
      currently doing well on follow-up.

PMID- 24027254
TI  - Robotic-arm stereotactic radiosurgery as a definitive treatment for gelastic
      epilepsy associated with hypothalamic hamartoma.
AB  - Gelastic seizures, characterised by paroxysms of pathological laughter, are most
      often associated with an underlying hypothalamic hamartoma. This report describes
      the definitive treatment using stereotactic-radiosurgery for a teenaged child
      whose gelastic epilepsy was found refractory to various antiepileptic drugs.
      Since surgery was not consented to, the child was referred to us for stereotactic
      radiosurgery (SRS), which was delivered with robotic-arm -SRS to a dose of 30 Gy
      in five fractions in five consecutive days. A decrease in the frequency of
      seizures was noticeable as early as within a week, and at 12 months after the
      procedure, there has been a total cessation of seizures.

PMID- 24027255
TI  - Hepatic hydrothorax in the absence of ascites.
AB  - A previously well 66-year-old woman presented with a recurrent transudative right
      sided pleural effusion. A nodular liver with coarse echotexture was demonstrated
      on ultrasound and subsequent MRI found hepatocellular carcinoma. In the absence
      of cardiopulmonary disease and significant protein uria, the recurrent pleural
      effusion was presumed to be hepatic hydrothorax despite the absence of ascites or
      other clinical features of chronic liver disease. The patient is currently
      awaiting liver transplantation.

PMID- 24027256
TI  - Visual failure in the elderly and dysphagia.
AB  - A 91-year-old man presented with a history of acute dysphagia. Clinical
      examination found reduced oxygen saturations and lung basal crepitations. Blood
      tests revealed mild anaemia, leukocytosis and acute renal failure. Chest X-ray
      demonstrated two oesophageal foreign bodies (FBs) and consolidation at the left
      lung base. Dysphagia resolved following the removal of two coins at
      oesophagogastroduodenoscopy, the man did not recall ingesting coins. His coin
      ingestion was attributed to poor visual acquity and he was referred for eye
      examination and advised to keep coins separate from food and medication. Children
      and the aged are likely to swallow FBs; causes of ingestion include reduced
      ability to chew and/or distinguish between objects. Most FBs pass spontaneously,
      however those that become stuck are likely to impact in the oesophagus. It is
      important to consider visual acuity for both compliance with medication and to
      prevent ingestion of FBs.

PMID- 24027257
TI  - Closing left gastroschisis with vanishing left testis.
AB  - We report a baby boy with gastroschisis with left non-palpable undescended testis
      who had a defect on the left side of an intact and normal umbilical cord and had
      associated testicular atrophy and abnormalities of the ductus deferens. They were
      successfully managed by primary repair and had uneventful recovery. Subsequent
      inguinal exploration confirmed blind ending vas deferens and vanishing left
      undescended testis. Our case confirms vascular accidents at the narrow abdominal
      wall defect can lead to vanishing testis following attempts at closing
      gastroschisis making the defect narrow and compromising the blood supply to the
      testis. 

PMID- 24027258
TI  - Hemophagocytic syndrome with atypical presentation in an adolescent.
AB  - A 14-year-old adolescent presented with a prolonged fever, abnormal liver
      function, anaemia, thrombocytopaenia, but a good general status. Diagnosis of
      hemophagocytic lymphohistiocytosis (HLH) was suspected, in spite of the initial
      indolent course. Secondary causes were excluded, but no specific mutation
      indicative of primary HLH was found. The patient started with specific therapy,
      but progressed with reactivations and later with persistently active disease.
      Haematopoietic stem cell transplantation was not successful and the adolescent
      died 7 months after diagnosis. 

PMID- 24027259
TI  - Isolated bilateral oculomotor nerve palsies due to a midbrain cavernous
      malformation.

PMID- 24027260
TI  - Exercise and sleep deprivation do not change cytokine expression levels in
      patients with chronic fatigue syndrome.
AB  - A major hypothesis regarding the cause of chronic fatigue syndrome (CFS) is
      immune dysregulation, thought to be reflected in upregulated proinflammatory
      cytokines leading to the symptoms that are characteristic of this illness.
      Because the symptoms worsen with physical exertion or sleep loss, we hypothesized
      that we could use these stressors to magnify the underlying potential pathogenic
      abnormalities in the cytokine systems of people with CFS. We conducted repeat
      blood sampling for cytokine levels from healthy subjects and CFS patients during
      both postexercise and total sleep deprivation nights and assayed for protein
      levels in the blood samples, mRNA activity in peripheral blood lymphocytes
      (PBLs), and function in resting and stimulated PBLs. We found that these
      environmental manipulations did not produce clinically significant upregulation
      of proinflammatory cytokines. These data do not support an important role of
      immune dysregulation in the genesis of stress-induced worsening of CFS. 

PMID- 24027261
TI  - Piliation of invasive Streptococcus pneumoniae isolates in the era before
      pneumococcal conjugate vaccine introduction in Malawi.
AB  - The pneumococcal pilus has been shown to be an important determinant of adhesion
      and virulence in mouse models of colonization, pneumonia, and bacteremia. A pilus
      is capable of inducing protective immunity, supporting its inclusion in next
      generation pneumococcal protein vaccine formulations. Whether this vaccine target
      is common among pneumococci in sub-Saharan Africa is uncertain. To define the
      prevalence and genetic diversity of type I and II pili among invasive pneumococci
      in Malawi prior to the introduction of the 13-valent pneumococcal conjugate
      vaccine (PCV13) into routine childhood immunization, we examined 188
      Streptococcus pneumoniae isolates collected between 2002 and 2008 (17% serotype
      1). In this region of high disease burden, we found a low frequency of invasive
      piliated pneumococci (14%) and pilus gene sequence diversity similar to that seen
      previously in multiple global pneumococcal lineages. All common serotypes with
      pilus were covered by PCV13 and so we predict that pilus prevalence will be
      reduced in the Malawian pneumococcal population after PCV13 introduction. 

PMID- 24027262
TI  - Mucosal immunization with high-mobility group box 1 in chitosan enhances DNA
      vaccine-induced protection against coxsackievirus B3-induced myocarditis.
AB  - Coxsackievirus B3 (CVB3), a small single-stranded RNA virus, belongs to the
      Picornaviridae family. Its infection is the most common cause of myocarditis,
      with no vaccine available. Gastrointestinal mucosa is the major entry port for
      CVB3; therefore, the induction of local immunity in mucosal tissues may help
      control initial viral infections and alleviate subsequent myocardial injury. Here
      we evaluated the ability of high-mobility group box 1 (HMGB1) encapsulated in
      chitosan particles to enhance the mucosal immune responses induced by the CVB3
      specific mucosal DNA vaccine chitosan-pVP1. Mice were intranasally coimmunized
      with 4 doses of chitosan-pHMGB1 and chitosan-pVP1 plasmids, at 2-week intervals,
      and were challenged with CVB3 4 weeks after the last immunization. Compared with
      chitosan-pVP1 immunization alone, coimmunization with chitosan-pHMGB1
      significantly (P < 0.05) enhanced CVB3-specific fecal secretory IgA levels and
      promoted mucosal T cell immune responses. In accordance, reduced severity of
      myocarditis was observed in coimmunized mice, as evidenced by significantly (P <
      0.05) reduced viral loads, decreased myocardial injury, and increased survival
      rates. Flow cytometric analysis indicated that HMGB1 enhanced dendritic cell (DC)
      recruitment to mesenteric lymph nodes and promoted DC maturation, which might
      partly account for its mucosal adjuvant effect. This strategy may represent a
      promising approach to candidate vaccines against CVB3-induced myocarditis. 

PMID- 24027263
TI  - Enhanced motion perception as a psychophysical marker for autism?

PMID- 24027264
TI  - Rapid recalibration to audiovisual asynchrony.
AB  - To combine information from different sensory modalities, the brain must deal
      with considerable temporal uncertainty. In natural environments, an external
      event may produce simultaneous auditory and visual signals yet they will
      invariably activate the brain asynchronously due to different propagation speeds
      for light and sound, and different neural response latencies once the signals
      reach the receptors. One strategy the brain uses to deal with audiovisual timing
      variation is to adapt to a prevailing asynchrony to help realign the signals.
      Here, using psychophysical methods in human subjects, we investigate audiovisual
      recalibration and show that it takes place extremely rapidly without explicit
      periods of adaptation. Our results demonstrate that exposure to a single, brief
      asynchrony is sufficient to produce strong recalibration effects. Recalibration
      occurs regardless of whether the preceding trial was perceived as synchronous,
      and regardless of whether a response was required. We propose that this rapid
      recalibration is a fast-acting sensory effect, rather than a higher-level
      cognitive process. An account in terms of response bias is unlikely due to a
      strong asymmetry whereby stimuli with vision leading produce bigger
      recalibrations than audition leading. A fast-acting recalibration mechanism
      provides a means for overcoming inevitable audiovisual timing variation and
      serves to rapidly realign signals at onset to maximize the perceptual benefits of
      audiovisual integration. 

PMID- 24027265
TI  - Defective escape behavior in DEAH-box RNA helicase mutants improved by restoring
      glycine receptor expression.
AB  - RNA helicases regulate RNA metabolism, but their substrate specificity and in
      vivo function remain largely unknown. We isolated spontaneous mutant zebrafish
      that exhibit an abnormal dorsal bend at the beginning of tactile-evoked escape
      swimming. Similar behavioral defects were observed in zebrafish embryos treated
      with strychnine, which blocks glycine receptors (GlyRs), suggesting that the
      abnormal motor response in mutants may be attributable to a deficit in
      glycinergic synaptic transmission. We identified a missense mutation in the gene
      encoding RNA helicase Dhx37. In Dhx37 mutants, ribosomal RNA levels were
      unchanged, whereas GlyR alpha1, alpha3, and alpha4a subunit mRNA levels were
      decreased due to a splicing defect. We found that Dhx37 can interact with GlyR
      alpha1, alpha3, and alpha4a transcripts but not with the GlyR alpha2 subunit
      mRNA. Overexpression of GlyR alpha1, alpha3, or alpha4a subunits in Dhx37
      deficient embryos restored normal behavior. Conversely, antisense-mediated
      knockdown of multiple GlyR alpha subunits in wild-type embryos was required to
      recapitulate the Dhx37 mutant phenotype. These results indicate that Dhx37 is
      specifically required for the biogenesis of a subset of GlyR alpha subunit mRNAs,
      thereby regulating glycinergic synaptic transmission and associated motor
      behaviors. To our knowledge, this is the first identification of pathologically
      relevant substrates for an RNA helicase. 

PMID- 24027267
TI  - Adult neurogenesis produces neurons with unique GABAergic synapses in the
      olfactory bulb.
AB  - Neuronal regeneration occurs naturally in a few restricted mammalian brain
      regions, but its functional significance remains debated. Here we search for
      unique features in the synaptic outputs made by adult-born granule cell
      interneurons in the mouse olfactory bulb using optogenetic targeting of specific
      neuronal ages. We find that adult-born interneurons are resistant to presynaptic
      GABA(B)-mediated depression of GABA release compared with interneurons born just
      after birth that exhibit strong GABA(B) neuromodulation. Correlated with this
      functional change, we found altered localization of the GGABA(B)R1 protein within
      adult-born granule cells. These results suggest that adult neurogenesis produces
      a population of functionally unique GABAergic synapses in the olfactory bulb.

PMID- 24027266
TI  - MiR-26b, upregulated in Alzheimer's disease, activates cell cycle entry, tau
      phosphorylation, and apoptosis in postmitotic neurons.
AB  - MicroRNA (miRNA) functions in the pathogenesis of major neurodegenerative
      diseases such as Alzheimer's disease (AD) are only beginning to emerge. We have
      observed significantly elevated levels of a specific miRNA, miR-26b, in the
      defined pathological areas of human postmortem brains, starting from early stages
      of AD (Braak III). Ectopic overexpression of miR-26b in rat primary postmitotic
      neurons led to the DNA replication and aberrant cell cycle entry (CCE) and, in
      parallel, increased tau-phosphorylation, which culminated in the apoptotic cell
      death of neurons. Similar tau hyperphosphorylation and CCE are typical features
      of neurons in pre-AD brains. Sequence-specific inhibition of miR-26b in culture
      is neuroprotective against oxidative stress. Retinoblastoma protein (Rb1), a
      major tumor suppressor, appears as the key direct miR-26b target, which mediates
      the observed neuronal phenotypes. The downstream signaling involves upregulation
      of Rb1/E2F cell cycle and pro-apoptotic transcriptional targets, including cyclin
      E1, and corresponding downregulation of cell cycle inhibitor p27/Kip1. It further
      leads to nuclear export and activation of Cdk5, a major kinase implicated in tau
      phosphorylation, regulation of cell cycle, and death in postmitotic neurons.
      Therefore, upregulation of miR-26b in neurons causes pleiotropic phenotypes that
      are also observed in AD. Elevated levels of miR-26b may thus contribute to the AD
      neuronal pathology. 

PMID- 24027268
TI  - c-Jun N-terminal kinase phosphorylation of heterogeneous nuclear
      ribonucleoprotein K regulates vertebrate axon outgrowth via a posttranscriptional
      mechanism.
AB  - c-Jun N-terminal kinase (JNK) mediates cell signaling essential for axon
      outgrowth, but the associated substrates and underlying mechanisms are poorly
      understood. We identified in Xenopus laevis embryos a novel posttranscriptional
      mechanism whereby JNK regulates axonogenesis by phosphorylating a specific site
      on heterogeneous nuclear ribonucleoprotein K (hnRNP K). Both JNK inhibition and
      hnRNP K knockdown inhibited axon outgrowth and translation of hnRNP K-regulated
      cytoskeletal RNAs (tau and neurofilament medium), effects that were alleviated by
      expressing phosphomimetic, but not phosphodeficient, forms of hnRNP K.
      Immunohistochemical and biochemical analyses indicated that JNK phosphorylation
      of hnRNP K occurred within the cytoplasm and was necessary for the translational
      initiation of hnRNP K-targeted RNAs but not for hnRNP K intracellular
      localization or RNA binding. Thus, in addition to its known roles in
      transcription and cytoskeletal organization, JNK acts posttranscriptionally
      through hnRNP K to regulate translation of proteins crucial for axonogenesis. 

PMID- 24027269
TI  - Lhx3-Chx10 reticulospinal neurons in locomotor circuits.
AB  - Motor behaviors result from the interplay between the brain and the spinal cord.
      Reticulospinal neurons, situated between the supraspinal structures that initiate
      motor movements and the spinal cord that executes them, play key integrative
      roles in these behaviors. However, the molecular identities of mammalian
      reticular formation neurons that mediate motor behaviors have not yet been
      determined, thus limiting their study in health and disease. In the medullary
      reticular formation of the mouse, we identified neurons that express the
      transcription factors Lhx3 and/or Chx10, and demonstrate that these neurons form
      a significant component of glutamatergic reticulospinal pathways. Lhx3-positive
      medullary reticular formation neurons express Fos following a locomotor task in
      the adult, indicating that they are active during walking. Furthermore, they
      receive functional inputs from the mesencephalic locomotor region and have
      electrophysiological properties to support tonic repetitive firing, both of which
      are necessary for neurons that mediate the descending command for locomotion.
      Together, these results suggest that Lhx3/Chx10 medullary reticular formation
      neurons are involved in locomotion. 

PMID- 24027270
TI  - Opiate exposure and withdrawal induces a molecular memory switch in the
      basolateral amygdala between ERK1/2 and CaMKIIalpha-dependent signaling
      substrates.
AB  - Opiate reward memories are powerful triggers for compulsive opiate-seeking
      behaviors. The basolateral amygdala (BLA) is an important structure for the
      processing of opiate-related associative memories and is functionally linked to
      the mesolimbic dopamine (DA) pathway. Transmission through intra-BLA DA D1-like
      and D2-like receptors independently modulates the formation of opiate reward
      memories as a function of opiate-exposure state. Thus, in the opiate-naive state,
      intra-BLA D1 transmission is required for opiate-related memory formation. Once
      opiate dependence and withdrawal has developed, a functional switch to a DA D2
      mediated memory mechanism takes place. However, the downstream molecular
      signaling events that control this functional switch between intra-BLA DA D1
      versus D2 receptor transmission are not currently understood. Using an unbiased
      place conditioning procedure in rats combined with molecular analyses, we report
      that opiate reward memory acquisition requires intra-BLA ERK1/2 signaling only in
      the previously opiate-naive state. However, following chronic opiate exposure and
      withdrawal, intra-BLA reward memory processing switches to a CaMKIIalpha
      dependent memory substrate. Furthermore, the ability of intra-BLA DA D1 or D2
      receptor transmission to modulate the motivational salience of opiates similarly
      operates through a D1-mediated ERK-dependent mechanism in the opiate-naive state,
      but switches to a D2-mediated CaMKIIalpha-dependent mechanism in the
      dependent/withdrawn state. Protein analysis of BLA tissue revealed a
      downregulation of ERK1/2 phosphorylation and a dramatic reduction in both total
      and phosphorylated CaMKIIalpha signaling, specifically in the opiate
      dependent/withdrawn state, demonstrating functional control of ERK1/2-dependent
      versus CaMKIIalpha-dependent memory mechanisms within the BLA, controlled by
      opiate-exposure state. 

PMID- 24027272
TI  - Emergence of sensory patterns during sleep highlights differential dynamics of
      REM and non-REM sleep stages.
AB  - Despite the profound reduction in conscious awareness associated with sleep,
      sensory cortex remains highly active during the different sleep stages,
      exhibiting complex interactions between different cortical sites. The potential
      functional significance of such spatial patterns and how they change between
      different sleep stages is presently unknown. In this electrocorticography study
      of human patients, we examined this question by studying spatial patterns of
      activity (broadband gamma power) that emerge during sleep (sleep patterns) and
      comparing them to the functional organization of sensory cortex that is activated
      by naturalistic stimuli during the awake state. Our results show a high
      correlation (p < 10(-4), permutation test) between the sleep spatial patterns and
      the functional organization found during wakefulness. Examining how the sleep
      patterns changed through the night highlighted a stage-specific difference,
      whereby the repertoire of such patterns was significantly larger during rapid eye
      movement (REM) sleep compared with non-REM stages. These results reveal that
      intricate spatial patterns of sensory functional organization emerge in a stage
      specific manner during sleep. 

PMID- 24027271
TI  - Abnormal striatal dopaminergic neurotransmission during rest and task production
      in spasmodic dysphonia.
AB  - Spasmodic dysphonia is a primary focal dystonia characterized by involuntary
      spasms in the laryngeal muscles during speech production. The pathophysiology of
      spasmodic dysphonia is thought to involve structural and functional abnormalities
      in the basal ganglia-thalamo-cortical circuitry; however, neurochemical
      correlates underpinning these abnormalities as well as their relations to
      spasmodic dysphonia symptoms remain unknown. We used positron emission tomography
      with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic
      neurotransmission at the resting state and during production of symptomatic
      sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We
      found that patients, compared to healthy controls, had bilaterally decreased RAC
      binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%,
      which was associated with decreased RAC displacement (RAC DeltaBP) in the left
      striatum during symptomatic speaking (group average difference 10.2%), but
      increased RAC DeltaBP in the bilateral striatum during asymptomatic tapping
      (group average difference 10.1%). Patients with more severe voice symptoms and
      subclinically longer reaction time to initiate the tapping sequence had greater
      RAC DeltaBP measures, while longer duration of spasmodic dysphonia was associated
      with a decrease in task-induced RAC DeltaBP. Decreased dopaminergic transmission
      during symptomatic speech production may represent a disorder-specific
      pathophysiological trait involved in symptom generation, whereas increased
      dopaminergic function during unaffected task performance may be explained by a
      compensatory adaptation of the nigrostriatal dopaminergic system possibly due to
      decreased striatal D2/D3 receptor availability. These changes can be linked to
      the clinical and subclinical features of spasmodic dysphonia and may represent
      the neurochemical basis of basal ganglia alterations in this disorder. 

PMID- 24027273
TI  - Alterations in endogenous opioid functional measures in chronic back pain.
AB  - The absence of consistent end organ abnormalities in many chronic pain syndromes
      has led to a search for maladaptive CNS mechanisms that may explain their
      clinical presentations and course. Here, we addressed the role of brain regional
      MU-opioid receptor-mediated neurotransmission, one of the best recognized
      mechanisms of pain regulation, in chronic back pain in human subjects. We
      compared MU-opioid receptor availability in vivo at baseline, during pain
      expectation, and with moderate levels of sustained pain in 16 patients with
      chronic nonspecific back pain (CNBP) and in 16 age- and gender-matched healthy
      control subjects, using the MU-opioid receptor-selective radioligand
      [(11)C]carfentanil and positron emission tomography. We found that CNBP patients
      showed baseline increases in thalamic MU-opioid receptor availability, contrary
      to a previously studied sample of patients diagnosed with fibromyalgia. During
      both pain expectation and sustained pain challenges, CNBP patients showed
      regional reductions in the capacity to activate this neurotransmitter system
      compared with their control sample, further associated with clinical pain and
      affective state ratings. Our results demonstrate heterogeneity in endogenous
      opioid system functional measures across pain conditions, and alterations in both
      receptor availability and endogenous opioid function in CNBP that are relevant to
      the clinical presentation of these patients and the effects of opioid analgesics
      on MU-opioid receptors. 

PMID- 24027274
TI  - Ontogeny of excitatory spinal neurons processing distinct somatic sensory
      modalities.
AB  - Spatial and temporal cues govern the genesis of a diverse array of neurons
      located in the dorsal spinal cord, including dI1-dI6, dIL(A), and dIL(B)
      subtypes, but their physiological functions are poorly understood. Here we
      generated a new line of conditional knock-out (CKO) mice, in which the homeobox
      gene Tlx3 was removed in dI5 and dIL(B) cells. In these CKO mice, development of
      a subset of excitatory neurons located in laminae I and II was impaired,
      including itch-related GRPR-expressing neurons, PKCgamma-expressing neurons, and
      neurons expressing three neuropeptide genes: somatostatin, preprotachykinin 1,
      and the gastrin-releasing peptide. These CKO mice displayed marked deficits in
      generating nocifensive motor behaviors evoked by a range of pain-related or itch
      related stimuli. The mutants also failed to exhibit escape response evoked by
      dynamic mechanical stimuli but retained the ability to sense innocuous cooling
      and/or warm. Thus, our studies provide new insight into the ontogeny of spinal
      neurons processing distinct sensory modalities.

PMID- 24027275
TI  - Repetition suppression and multi-voxel pattern similarity differentially track
      implicit and explicit visual memory.
AB  - Repeated exposure to a visual stimulus is associated with corresponding
      reductions in neural activity, particularly within visual cortical areas. It has
      been argued that this phenomenon of repetition suppression is related to
      increases in processing fluency or implicit memory. However, repetition of a
      visual stimulus can also be considered in terms of the similarity of the pattern
      of neural activity elicited at each exposure--a measure that has recently been
      linked to explicit memory. Despite the popularity of each of these measures,
      direct comparisons between the two have been limited, and the extent to which
      they differentially (or similarly) relate to behavioral measures of memory has
      not been clearly established. In the present study, we compared repetition
      suppression and pattern similarity as predictors of both implicit and explicit
      memory. Using functional magnetic resonance imaging, we scanned 20 participants
      while they viewed and categorized repeated presentations of scenes. Repetition
      priming (facilitated categorization across repetitions) was used as a measure of
      implicit memory, and subsequent scene recognition was used as a measure of
      explicit memory. We found that repetition priming was predicted by repetition
      suppression in prefrontal, parietal, and occipitotemporal regions; however,
      repetition priming was not predicted by pattern similarity. In contrast,
      subsequent explicit memory was predicted by pattern similarity (across
      repetitions) in some of the same occipitotemporal regions that exhibited a
      relationship between priming and repetition suppression; however, explicit memory
      was not related to repetition suppression. This striking double dissociation
      indicates that repetition suppression and pattern similarity differentially track
      implicit and explicit learning.

PMID- 24027276
TI  - Subthalamic nucleus local field potential activity during the Eriksen flanker
      task reveals a novel role for theta phase during conflict monitoring.
AB  - The subthalamic nucleus (STN) is thought to play a central role in modulating
      responses during conflict. Computational models have suggested that the location
      of the STN in the basal ganglia, as well as its numerous connections to conflict
      related cortical structures, allows it to be ideally situated to act as a global
      inhibitor during conflict. Additionally, recent behavioral experiments have shown
      that deep brain stimulation to the STN results in impulsivity during high
      conflict situations. However, the precise mechanisms that mediate the "hold-your
      horses" function of the STN remain unclear. We recorded from deep brain
      stimulation electrodes implanted bilaterally in the STN of 13 human subjects with
      Parkinson's disease while they performed a flanker task. The incongruent trials
      with the shortest reaction times showed no behavioral or electrophysiological
      differences from congruent trials, suggesting that the distracter stimuli were
      successfully ignored. In these trials, cue-locked STN theta band activity
      demonstrated phase alignment across trials and was followed by a periresponse
      increase in theta power. In contrast, incongruent trials with longer reaction
      times demonstrated a relative reduction in theta phase alignment followed by
      higher theta power. Theta phase alignment negatively correlated with subject
      reaction time, and theta power positively correlated with trial reaction time.
      Thus, when conflicting stimuli are not properly ignored, disruption of STN theta
      phase alignment may help operationalize the hold-your-horses role of the nucleus,
      whereas later increases in the amplitude of theta oscillations may help overcome
      this function. 

PMID- 24027277
TI  - Deficiency of p62/Sequestosome 1 causes hyperphagia due to leptin resistance in
      the brain.
AB  - The cytoplasmic regulatory protein p62 (Sequestosome 1/A170) is known to modulate
      various receptor-mediated intracellular signaling pathways. p62 deficiency was
      shown to result in mature-onset obesity in mice, but the mechanisms underlying
      this abnormality remained unclear. Here we report that hyperphagia due to central
      leptin resistance is the cause of obesity in p62(-/-) mice. We found that these
      mice show hyperphagia. Restriction of food to the amount eaten by wild-type mice
      prevented excess body weight gain and fat accumulation, suggesting that
      overfeeding is the primary cause of obesity in p62(-/-) mice. Brain-specific p62
      deficiency caused mature-onset obesity to the same extent as in p62(-/-) mice,
      further supporting a neuronal mechanism as the major cause of obesity in these
      mice. Immunohistochemical analysis revealed that p62 is highly expressed in
      hypothalamic neurons, including POMC neurons in the arcuate nucleus. Central
      leptin resistance was observed even in young preobese p62(-/-) mice. We found a
      defect in intracellular distribution of the transcription factor Stat3, which is
      essential for the action of leptin, in p62(-/-) mice. These results indicate that
      brain p62 plays an important role in bodyweight control by modulating the central
      leptin-signaling pathway and that lack of p62 in the brain causes leptin
      resistance, leading to hyperphagia. Thus, p62 could be a clinical target for
      treating obesity and metabolic syndrome. 

PMID- 24027278
TI  - WldS and PGC-1alpha regulate mitochondrial transport and oxidation state after
      axonal injury.
AB  - Mitochondria carry out many of the processes implicated in maintaining axon
      health or causing axon degeneration, including ATP and reactive oxygen species
      (ROS) generation, as well as calcium buffering and protease activation. Defects
      in mitochondrial function and transport are common in axon degeneration, but how
      changes in specific mitochondrial properties relate to degeneration is not well
      understood. Using cutaneous sensory neurons of living larval zebrafish as a
      model, we examined the role of mitochondria in axon degeneration by monitoring
      mitochondrial morphology, transport, and redox state before and after laser
      axotomy. Mitochondrial transport terminated locally after injury in wild-type
      axons, an effect that was moderately attenuated by expressing the axon-protective
      fusion protein Wallerian degeneration slow (WldS). However, mitochondrial
      transport arrest eventually occurred in WldS-protected axons, indicating that
      later in the lag phase, mitochondrial transport is not required for axon
      protection. By contrast, the redox-sensitive biosensor roGFP2 was rapidly
      oxidized in the mitochondrial matrix after injury, and WldS expression prevented
      this effect, suggesting that stabilization of ROS production may mediate axon
      protection. Overexpression of PGC-1alpha, a transcriptional coactivator with
      roles in both mitochondrial biogenesis and ROS detoxification, dramatically
      increased mitochondrial density, attenuated roGFP2 oxidation, and delayed
      Wallerian degeneration. Collectively, these results indicate that mitochondrial
      oxidation state is a more reliable indicator of axon vulnerability to
      degeneration than mitochondrial motility. 

PMID- 24027279
TI  - Dynein-dependent transport of nanos RNA in Drosophila sensory neurons requires
      Rumpelstiltskin and the germ plasm organizer Oskar.
AB  - Intracellular mRNA localization is a conserved mechanism for spatially regulating
      protein production in polarized cells, such as neurons. The mRNA encoding the
      translational repressor Nanos (Nos) forms ribonucleoprotein (RNP) particles that
      are dendritically localized in Drosophila larval class IV dendritic arborization
      (da) neurons. In nos mutants, class IV da neurons exhibit reduced dendritic
      branching complexity, which is rescued by transgenic expression of wild-type nos
      mRNA but not by a localization-compromised nos derivative. While localization is
      essential for nos function in dendrite morphogenesis, the mechanism underlying
      the transport of nos RNP particles was unknown. We investigated the mechanism of
      dendritic nos mRNA localization by analyzing requirements for nos RNP particle
      motility in class IV da neuron dendrites through live imaging of fluorescently
      labeled nos mRNA. We show that dynein motor machinery components mediate
      transport of nos mRNA in proximal dendrites. Two factors, the RNA-binding protein
      Rumpelstiltskin and the germ plasm protein Oskar, which are required for
      diffusion/entrapment-mediated localization of nos during oogenesis, also function
      in da neurons for formation and transport of nos RNP particles. Additionally, we
      show that nos regulates neuronal function, most likely independent of its
      dendritic localization and function in morphogenesis. Our results reveal
      adaptability of localization factors for regulation of a target transcript in
      different cellular contexts. 

PMID- 24027280
TI  - P2X receptor intermediate activation states have altered nucleotide selectivity.
AB  - Purinergic P2X receptors are widely distributed in the nervous system and are
      known to play roles in primary afferent transmission and central respiratory
      regulation. They are trimeric membrane proteins, with the extracellular domain
      that provides three intersubunit ATP binding sites. We expressed the rat P2X7
      receptor in human embryonic kidney cells and measured membrane currents before
      and after photo-affinity labeling with the agonist 2'(3')-O-(4-benzoylbenzoyl)
      ATP (BzATP). After tethering BzATP with ultraviolet light, a persistent current
      remained after washing out the agonist. Additional current could now be elicited
      by other nucleotides (CTP and ADP) that are not normally effective as P2X
      receptor agonists. Similar results were obtained at P2X2 receptors even without
      previous agonist tethering: exposure to low concentrations of ATP caused the
      receptor to become sensitive to activation by CTP and ADP. The results show that
      ATP binding to the first of the three binding sites causes a conformational
      change to an intermediate closed state that shows increased effectiveness of
      pyrimidine and diphosphate nucleotide analogs. 

PMID- 24027281
TI  - Endothelial VEGF sculpts cortical cytoarchitecture.
AB  - Current models of brain development support the view that VEGF, a signaling
      protein secreted by neuronal cells, regulates angiogenesis and neuronal
      development. Here we demonstrate an autonomous and pivotal role for endothelial
      cell-derived VEGF that has far-reaching consequences for mouse brain development.
      Selective deletion of Vegf from endothelial cells resulted in impaired
      angiogenesis and marked perturbation of cortical cytoarchitecture. Abnormal cell
      clusters or heterotopias were detected in the marginal zone, and disorganization
      of cortical cells induced several malformations, including aberrant cortical
      lamination. Critical events during brain development-neuronal proliferation,
      differentiation, and migration were significantly affected. In addition, axonal
      tracts in the telencephalon were severely defective in the absence of endothelial
      VEGF. The unique roles of endothelial VEGF cannot be compensated by neuronal VEGF
      and underscores the high functional significance of endothelial VEGF for cerebral
      cortex development and from disease perspectives. 

PMID- 24027284
TI  - Inhibiting subthalamic D5 receptor constitutive activity alleviates abnormal
      electrical activity and reverses motor impairment in a rat model of Parkinson's
      disease.
AB  - Burst firing has been reported as a pathological activity of subthalamic nucleus
      (STN) neurons in Parkinson's disease. However, the origin of bursts and their
      causal link with motor deficits remain unknown. Here we tested the hypothesis
      that dopamine D5 receptors (D5Rs), characterized by a high constitutive activity,
      may contribute to the emergence of burst firing in STN. We tested whether
      inhibiting D5R constitutive activity depresses burst firing and alleviates motor
      impairments in the 6-OHDA rat model of Parkinson's disease. Intrasubthalamic
      microinjections of either an inverse agonist of D5Rs, flupenthixol, or a D2R
      antagonist, raclopride, were applied. Behavioral experiments, in vivo and in
      vitro electrophysiological recordings, and ex vivo functional neuroanatomy
      studies were performed. Using [(5)S]GTPgamma binding autoradiography, we show
      that application of flupenthixol inhibits D5R constitutive activity within the
      STN. Furthermore, flupenthixol reduced evoked burst in brain slices and converted
      pathological burst firing into physiological tonic, single-spike firing in 6-OHDA
      rats in vivo. This later action was mimicked by calciseptine, a Cav1 channel
      blocker. Moreover, the same treatment dramatically attenuated motor impairment in
      this model and normalized metabolic hyperactivity in both STN and substantia
      nigra pars reticulata, the main output structure of basal ganglia in rats. In
      contrast, raclopride as well as saline did not reverse burst firing and motor
      deficits, confirming the selective action of flupenthixol on D5Rs. These results
      are the first to demonstrate that subthalamic D5Rs are involved in the
      pathophysiology of Parkinson's disease and that administering an inverse agonist
      of these receptors may lessen motor symptoms. 

PMID- 24027283
TI  - The pattern of cortical dysfunction in a mouse model of a schizophrenia-related
      microdeletion.
AB  - We used a mouse model of the schizophrenia-predisposing 22q11.2 microdeletion to
      evaluate how this genetic lesion affects cortical neural circuits at the
      synaptic, cellular, and molecular levels. Guided by cognitive deficits, we
      demonstrated that mutant mice display robust deficits in high-frequency synaptic
      transmission and short-term plasticity (synaptic depression and potentiation), as
      well as alterations in long-term plasticity and dendritic spine stability. Apart
      from previously reported reduction in dendritic complexity of layer 5 pyramidal
      neurons, altered synaptic plasticity occurs in the context of relatively
      circumscribed and often subtle cytoarchitectural changes in neuronal density and
      inhibitory neuron numbers. We confirmed the pronounced DiGeorge critical region 8
      (Dgcr8)-dependent deficits in primary micro-RNA processing and identified
      additional changes in gene expression and RNA splicing that may underlie the
      effects of this mutation. Reduction in Dgcr8 levels appears to be a major driver
      of altered short-term synaptic plasticity in prefrontal cortex and working memory
      but not of long-term plasticity and cytoarchitecture. Our findings inform the
      cortical synaptic and neuronal mechanisms of working memory impairment in the
      context of psychiatric disorders. They also provide insight into the link between
      micro-RNA dysregulation and genetic liability to schizophrenia and cognitive
      dysfunction. 

PMID- 24027285
TI  - Extrasynaptic GABA(A) receptors couple presynaptic activity to postsynaptic
      inhibition in the somatosensory thalamus.
AB  - Thalamocortical circuits govern cognitive, sensorimotor, and sleep-related
      network processes, and generate pathological activities during absence epilepsy.
      Inhibitory control of thalamocortical (TC) relay neurons is partially mediated by
      GABA released from neurons of the thalamic reticular nucleus (nRT), acting
      predominantly via synaptic alpha1beta2gamma2 GABA(A) receptors (GABA(A)Rs).
      Importantly, TC neurons also express extrasynaptic alpha4beta2delta GABA(A)Rs,
      although how they cooperate with synaptic GABA(A)Rs to influence relay cell
      inhibition, particularly during physiologically relevant nRT output, is unknown.
      To address this question, we performed paired whole-cell recordings from
      synaptically coupled nRT and TC neurons of the ventrobasal (VB) complex in brain
      slices derived from wild-type and extrasynaptic GABA(A)R-lacking, alpha4 "knock
      out" (alpha4(0/0)) mice. We demonstrate that the duration of VB phasic inhibition
      generated in response to nRT burst firing is greatly reduced in alpha4(0/0)
      pairs, suggesting that action potential-dependent phasic inhibition is prolonged
      by recruitment of extrasynaptic GABA(A)Rs. Furthermore, the influence of nRT
      tonic firing frequency on VB holding current is also greatly reduced in
      alpha4(0/0) pairs, implying that the alpha4-GABA(A)R-mediated tonic conductance
      of relay neurons is dynamically influenced, in an activity-dependent manner, by
      nRT tonic firing intensity. Collectively, our data reveal that extrasynaptic
      GABA(A)Rs of the somatosensory thalamus do not merely provide static tonic
      inhibition but can also be dynamically engaged to couple presynaptic activity to
      postsynaptic excitability. Moreover, these processes are highly sensitive to the
      delta-selective allosteric modulator, DS2 and manipulation of GABA transport
      systems, revealing novel opportunities for therapeutic intervention in
      thalamocortical network disorders.

PMID- 24027282
TI  - Neutrophils express oncomodulin and promote optic nerve regeneration.
AB  - Although neurons are normally unable to regenerate their axons after injury to
      the CNS, this situation can be partially reversed by activating the innate immune
      system. In a widely studied instance of this phenomenon, proinflammatory agents
      have been shown to cause retinal ganglion cells, the projection neurons of the
      eye, to regenerate lengthy axons through the injured optic nerve. However, the
      role of different molecules and cell populations in mediating this phenomenon
      remains unclear. We show here that neutrophils, the first responders of the
      innate immune system, play a central role in inflammation-induced regeneration.
      Numerous neutrophils enter the mouse eye within a few hours of inducing an
      inflammatory reaction and express high levels of the atypical growth factor
      oncomodulin (Ocm). Immunodepletion of neutrophils diminished Ocm levels in the
      eye without altering levels of CNTF, leukemia inhibitory factor, or IL-6, and
      suppressed the proregenerative effects of inflammation. A peptide antagonist of
      Ocm suppressed regeneration as effectively as neutrophil depletion. Macrophages
      enter the eye later in the inflammatory process but appear to be insufficient to
      stimulate extensive regeneration in the absence of neutrophils. These data
      provide the first evidence that neutrophils are a major source of Ocm and can
      promote axon regeneration in the CNS. 

PMID- 24027286
TI  - Endocannabinoids in the brainstem modulate dural trigeminovascular nociceptive
      traffic via CB1 and "triptan" receptors: implications in migraine.
AB  - Activation and sensitization of trigeminovascular nociceptive pathways is
      believed to contribute to the neural substrate of the severe and throbbing nature
      of pain in migraine. Endocannabinoids, as well as being physiologically
      analgesic, are known to inhibit dural trigeminovascular nociceptive responses.
      They are also involved in the descending modulation of cutaneous-evoked C-fiber
      spinal nociceptive responses from the brainstem. The purpose of this study was to
      determine whether endocannabinoids are involved in the descending modulation of
      dural and/or cutaneous facial trigeminovascular nociceptive responses, from the
      brainstem ventrolateral periaqueductal gray (vlPAG). CB1 receptor activation in
      the vlPAG attenuated dural-evoked Adelta-fiber neurons (maximally by 19%) and
      basal spontaneous activity (maximally by 33%) in the rat trigeminocervical
      complex, but there was no effect on cutaneous facial receptive field responses.
      This inhibitory vlPAG-mediated modulation was inhibited by specific CB1 receptor
      antagonism, given via the vlPAG, and with a 5-HT1B/1D receptor antagonist, given
      either locally in the vlPAG or systemically. These findings demonstrate for the
      first time that brainstem endocannabinoids provide descending modulation of both
      basal trigeminovascular neuronal tone and Adelta-fiber dural-nociceptive
      responses, which differs from the way the brainstem modulates spinal nociceptive
      transmission. Furthermore, our data demonstrate a novel interaction between
      serotonergic and endocannabinoid systems in the processing of somatosensory
      nociceptive information, suggesting that some of the therapeutic action of
      triptans may be via endocannabinoid containing neurons in the vlPAG. 

PMID- 24027287
TI  - P-selectin-mediated monocyte-cerebral endothelium adhesive interactions link
      peripheral organ inflammation to sickness behaviors.
AB  - Sickness behaviors, such as fatigue, mood alterations, and cognitive dysfunction,
      which result from changes in central neurotransmission, are prevalent in systemic
      inflammatory diseases and greatly impact patient quality of life. Although,
      microglia (resident cerebral immune cells) and cytokines (e.g., TNFalpha) are
      associated with changes in central neurotransmission, the link between peripheral
      organ inflammation, circulating cytokine signaling, and microglial activation
      remains poorly understood. Here we demonstrate, using cerebral intravital
      microscopy, that in response to liver inflammation, there is increased monocyte
      specific rolling and adhesion along cerebral endothelial cells (CECs). Peripheral
      TNFalpha-TNFR1 signaling and the adhesion molecule P-selectin are central
      mediators of these monocyte-CEC adhesive interactions which were found to be
      closely associated with microglial activation, decreased central neural
      excitability and sickness behavior development. Similar monocyte-CEC adhesive
      interactions were also observed in another mouse model of peripheral organ
      inflammation (i.e., 2,4-dinitrobenzene sulfonic acid-induced colitis). Our
      observations provide a clear link between peripheral organ inflammation and
      cerebral changes that impact behavior, which can potentially allow for novel
      therapeutic interventions in patients with systemic inflammatory diseases. 

PMID- 24027288
TI  - Transgenically targeted rabies virus demonstrates a major monosynaptic projection
      from hippocampal area CA2 to medial entorhinal layer II neurons.
AB  - The enormous potential of modern molecular neuroanatomical tools lies in their
      ability to determine the precise connectivity of the neuronal cell types
      comprising the innate circuitry of the brain. We used transgenically targeted
      viral tracing to identify the monosynaptic inputs to the projection neurons of
      layer II of medial entorhinal cortex (MEC-LII) in mice. These neurons are not
      only major inputs to the hippocampus, the structure most clearly implicated in
      learning and memory, they also are "grid cells." Here we address the question of
      what kinds of inputs are specifically targeting these MEC-LII cells. Cell
      specific infection of MEC-LII with recombinant rabies virus results in
      unambiguous labeling of monosynaptic inputs. Furthermore, ratios of labeled
      neurons in different regions are largely consistent between animals, suggesting
      that label reflects density of innervation. While the results mostly confirm
      prior anatomical work, they also reveal a novel major direct input to MEC-LII
      from hippocampal pyramidal neurons. Interestingly, the vast majority of these
      direct hippocampal inputs arise not from the major hippocampal subfields of CA1
      and CA3, but from area CA2, a region that has historically been thought to merely
      be a transitional zone between CA3 and CA1. We confirmed this unexpected result
      using conventional tracing techniques in both rats and mice. 

PMID- 24027289
TI  - Transfer of cognitive training across magnitude dimensions achieved with
      concurrent brain stimulation of the parietal lobe.
AB  - Improvement in performance following cognitive training is known to be further
      enhanced when coupled with brain stimulation. Here we ask whether training
      induced changes can be maintained long term and, crucially, whether they can
      extend to other related but untrained skills. We trained overall 40 human
      participants on a simple and well established paradigm assessing the ability to
      discriminate numerosity--or the number of items in a set--which is thought to
      rely on an "approximate number sense" (ANS) associated with parietal lobes. We
      coupled training with parietal stimulation in the form of transcranial random
      noise stimulation (tRNS), a noninvasive technique that modulates neural activity.
      This yielded significantly better and longer lasting improvement (up to 16 weeks
      post-training) of the precision of the ANS compared with cognitive training in
      absence of stimulation, stimulation in absence of cognitive training, and
      cognitive training coupled to stimulation to a control site (motor areas).
      Critically, only ANS improvement induced by parietal tRNS + Training transferred
      to proficiency in other parietal lobe-based quantity judgment, i.e., time and
      space discrimination, but not to quantity-unrelated tasks measuring attention,
      executive functions, and visual pattern recognition. These results indicate that
      coupling intensive cognitive training with tRNS to critical brain regions
      resulted not only in the greatest and longer lasting improvement of numerosity
      discrimination, but importantly in this enhancement being transferable when
      trained and untrained abilities are carefully chosen to share common cognitive
      and neuronal components.

PMID- 24027290
TI  - Forebrain deletion of the vesicular acetylcholine transporter results in deficits
      in executive function, metabolic, and RNA splicing abnormalities in the
      prefrontal cortex.
AB  - One of the key brain regions in cognitive processing and executive function is
      the prefrontal cortex (PFC), which receives cholinergic input from basal
      forebrain cholinergic neurons. We evaluated the contribution of synaptically
      released acetylcholine (ACh) to executive function by genetically targeting the
      vesicular acetylcholine transporter (VAChT) in the mouse forebrain. Executive
      function was assessed using a pairwise visual discrimination paradigm and the 5
      choice serial reaction time task (5-CSRT). In the pairwise test, VAChT-deficient
      mice were able to learn, but were impaired in reversal learning, suggesting that
      these mice present cognitive inflexibility. Interestingly, VAChT-targeted mice
      took longer to reach criteria in the 5-CSRT. Although their performance was
      indistinguishable from that of control mice during low attentional demand,
      increased attentional demand revealed striking deficits in VAChT-deleted mice.
      Galantamine, a cholinesterase inhibitor used in Alzheimer's disease,
      significantly improved the performance of control mice, but not of VAChT
      deficient mice on the 5-CSRT. In vivo magnetic resonance spectroscopy showed
      altered levels of two neurochemical markers of neuronal function, taurine and
      lactate, suggesting altered PFC metabolism in VAChT-deficient mice. The PFC of
      these mice displayed a drastic reduction in the splicing factor heterogeneous
      nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), whose cholinergic-mediated
      reduction was previously demonstrated in Alzheimer's disease. Consequently,
      several key hnRNPA2/B1 target transcripts involved in neuronal function present
      changes in alternative splicing in VAChT-deficient mice, including pyruvate
      kinase M, a key enzyme involved in lactate metabolism. We propose that VAChT
      targeted mice can be used to model and to dissect the neurochemical basis of
      executive abnormalities. 

PMID- 24027291
TI  - Informational basis of sensory adaptation: entropy and single-spike efficiency in
      rat barrel cortex.
AB  - We showed recently that exposure to whisker vibrations enhances coding efficiency
      in rat barrel cortex despite increasing correlations in variability (Adibi et
      al., 2013). Here, to understand how adaptation achieves this improvement in
      sensory representation, we decomposed the stimulus information carried in
      neuronal population activity into its fundamental components in the framework of
      information theory. In the context of sensory coding, these components are the
      entropy of the responses across the entire stimulus set (response entropy) and
      the entropy of the responses conditional on the stimulus (conditional response
      entropy). We found that adaptation decreased response entropy and conditional
      response entropy at both the level of single neurons and the pooled activity of
      neuronal populations. However, the net effect of adaptation was to increase the
      mutual information because the drop in the conditional entropy outweighed the
      drop in the response entropy. The information transmitted by a single spike also
      increased under adaptation. As population size increased, the information content
      of individual spikes declined but the relative improvement attributable to
      adaptation was maintained. 

PMID- 24027292
TI  - Dynamic tuning of electrical and chemical synaptic transmission in a network of
      motion coding retinal neurons.
AB  - Recently, we demonstrated that gap junction coupling in the population of
      superior coding ON-OFF directionally selective ganglion cells (DSGCs) genetically
      labeled in the Hb9::eGFP mouse retina allows the passage of lateral anticipatory
      signals that help track moving stimuli. Here, we examine the properties of gap
      junctions in the DSGC network, and address how interactions between electrical
      and chemical synapses and intrinsic membrane properties contribute to the dynamic
      tuning of lateral anticipatory signals. When DSGC subtypes coding all four
      cardinal directions were individually loaded with the gap junction-permeable
      tracer Neurobiotin, only superior coding DSGCs exhibited homologous coupling.
      Consistent with these anatomical findings, gap junction-dependent feedback
      spikelets were only observed in Hb9(+) DSGCs. Recordings from pairs of
      neighboring Hb9(+) DSGCs revealed that coupling was reciprocal, non-inactivating,
      and relatively weak, and provided a substrate for an extensive subthreshold
      excitatory receptive field around each cell. This subthreshold activity appeared
      to boost coincident light-driven chemical synaptic responses. However, during
      responses to moving stimuli, gap junction-mediated boosting appeared to be
      dynamically modulated such that upstream DSGCs primed downstream cells, but not
      vice versa, giving rise to highly skewed responses in individual cells. We show
      that the asymmetry in priming arises from a combination of spatially offset
      GABAergic inhibition and activity-dependent changes in intrinsic membrane
      properties of DSGCs. Thus, dynamic interactions between electrical and chemical
      synapses and intrinsic membrane properties allow the network of DSGCs to
      propagate anticipatory responses most effectively along their preferred direction
      without leading to runaway excitation. 

PMID- 24027294
TI  - Effects of cathodal trans-spinal direct current stimulation on mouse spinal
      network and complex multijoint movements.
AB  - Cathodal trans-spinal direct current (c-tsDC) stimulation is a powerful technique
      to modulate spinal excitability. However, the manner in which c-tsDC stimulation
      modulates cortically evoked simple single-joint and complex multijoint movements
      is unknown. To address this issue, anesthetized mice were suspended with the
      hindlimb allowed to move freely in space. Simple and complex multijoint movements
      were elicited with short and prolonged trains of electrical stimulation,
      respectively, delivered to the area of primary motor cortex representing the
      hindlimb. In addition, spinal cord burst generators are known to be involved in a
      variety of motor activities, including locomotion, postural control, and
      voluntary movements. Therefore, to shed light into the mechanisms underlying
      movements modulated by c-tsDC stimulation, spinal circuit activity was induced
      using GABA and glycine receptor blockers, which produced three rates of spinal
      bursting activity: fast, intermediate, and slow. Characteristics of bursting
      activity were assessed during c-tsDC stimulation. During c-tsDC stimulation,
      significant increases were observed in (1) ankle dorsiflexion amplitude and
      speed; (2) ankle plantarflexion amplitude, speed, and duration; and (3) complex
      multijoint movement amplitude, speed, and duration. However, complex multijoint
      movement tracing showed that c-tsDC did not change the form of movements. In
      addition, spinal bursting activity was significantly modulated during c-tsDC
      stimulation: (1) fast bursting activity showed increased rate, amplitude, and
      duration; (2) intermediate bursting activity showed increased rate and duration,
      but decreased amplitude; and (3) slow bursting activity showed increased rate,
      but decreased duration and amplitude. These results suggest that c-tsDC
      stimulation amplifies cortically evoked movements through spinal mechanisms. 

PMID- 24027293
TI  - cGMP accumulation causes photoreceptor degeneration in CNG channel deficiency:
      evidence of cGMP cytotoxicity independently of enhanced CNG channel function.
AB  - Photoreceptor cyclic nucleotide-gated (CNG) channels regulate Ca(2+) influx in
      rod and cone photoreceptors. cGMP, the native ligand of the photoreceptor CNG
      channels, has been associated with cytotoxicity when its levels rise above normal
      due to defects in photoreceptor phosphodiesterase (PDE6) or regulation of retinal
      guanylyl cyclase (retGC). We found a massive accumulation of cGMP in CNGA3
      deficient retina and investigated whether cGMP accumulation plays a role in cone
      degeneration in CNG channel deficiency. The time course study showed that the
      retinal cGMP level in Cnga3(-/-);Nrl(-/-) mice with CNGA3 deficiency on a cone
      dominant background was sharply increased at postnatal day 8 (P8), peaked around
      P10-P15, remained high through P30-P60, and returned to near control level at
      P90. This elevation pattern correlated with photoreceptor apoptotic death, which
      peaked around P15-P20. In Cnga3(-/-);Gucy2e(-/-) mice lacking retGC1, cone
      density and expression levels of cone-specific proteins were significantly
      increased compared with Cnga3(-/-), consistent with a role of cGMP accumulation
      as the major contributor to cone death caused by CNG channel deficiency. The
      activity and expression levels of cGMP-dependent protein kinase G (PKG) were
      significantly increased in Cnga3(-/-);Nrl(-/-) retina compared with Nrl(-/-),
      suggesting an involvement of PKG regulation in cell death. Our results indicate
      that cGMP accumulation in photoreceptors can itself exert cytotoxic effect in
      cones, independently of CNG channel activity and Ca(2+) influx. 

PMID- 24027296
TI  - Retraction: Hires et al, Whisker dynamics underlying tactile exploration.

PMID- 24027295
TI  - Interacting linear and nonlinear characteristics produce population coding
      asymmetries between ON and OFF cells in the retina.
AB  - The early visual system is a model for understanding the roles of cell
      populations in parallel processing. Cells in this system can be classified
      according to their responsiveness to different stimuli; a prominent example is
      the division between cells that respond to stimuli of opposite contrasts (ON vs
      OFF cells). These two cell classes display many asymmetries in their
      physiological characteristics (including temporal characteristics, spatial
      characteristics, and nonlinear characteristics) that, individually, are known to
      have important roles in population coding. Here we describe a novel distinction
      between the information that ON and OFF ganglion cell populations carry in mouse-
      that OFF cells are able to signal motion information about both light and dark
      objects, while ON cells have a selective deficit at signaling the motion of dark
      objects. We found that none of the previously reported asymmetries in
      physiological characteristics could account for this distinction. We therefore
      analyzed its basis via a recently developed linear-nonlinear-Poisson model that
      faithfully captures input/output relationships for a broad range of stimuli
      (Bomash et al., 2013). While the coding differences between ON and OFF cell
      populations could not be ascribed to the linear or nonlinear components of the
      model individually, they had a simple explanation in the way that these
      components interact. Sensory transformations in other systems can likewise be
      described by these models, and thus our findings suggest that similar
      interactions between component properties may help account for the roles of cell
      classes in population coding more generally.

PMID- 24027297
TI  - Mutation profile of the GNE gene in Japanese patients with distal myopathy with
      rimmed vacuoles (GNE myopathy).
AB  - BACKGROUND: GNE myopathy (also called distal myopathy with rimmed vacuoles or
      hereditary inclusion body myopathy) is an autosomal recessive myopathy
      characterised by skeletal muscle atrophy and weakness that preferentially involve
      the distal muscles. It is caused by mutations in the gene encoding a key enzyme
      in sialic acid biosynthesis, UDP-N-acetylglucosamine 2-epimerase/N
      acetylmannosamine kinase (GNE). METHODS: We analysed the GNE gene in 212 Japanese
      GNE myopathy patients. A retrospective medical record review was carried out to
      explore genotype-phenotype correlation. RESULTS: Sixty-three different mutations
      including 25 novel mutations were identified: 50 missense mutations, 2 nonsense
      mutations, 1 insertion, 4 deletions, 5 intronic mutations and 1 single exon
      deletion. The most frequent mutation in the Japanese population is c.1714G>C
      (p.Val572Leu), which accounts for 48.3% of total alleles. Homozygosity for this
      mutation results in more severe phenotypes with earlier onset and faster
      progression of the disease. In contrast, the second most common mutation,
      c.527A>T (p.Asp176Val), seems to be a mild mutation as the onset of the disease
      is much later in the compound heterozygotes with this mutation and c.1714G>C than
      the patients homozygous for c.1714G>C. Although the allele frequency is 22.4%,
      there are only three homozygotes for c.527A>T, raising a possibility that a
      significant number of c.527A>T homozygotes may not develop an apparent disease.
      CONCLUSIONS: Here, we report the mutation profile of the GNE gene in 212 Japanese
      GNE myopathy patients, which is the largest single-ethnic cohort for this ultra
      orphan disease. We confirmed the clinical difference between mutation groups.
      However, we should note that the statistical summary cannot predict clinical
      course of every patient.

PMID- 24027298
TI  - Spreading of amyotrophic lateral sclerosis lesions--multifocal hits and local
      propagation?
AB  - OBJECTIVE: To investigate whether or not the lesions in sporadic amyotrophic
      lateral sclerosis (ALS) originate from a single focal onset site and spread
      contiguously by prion-like cell-to-cell propagation in the rostrocaudal direction
      along the spinal cord, as has been hypothesised (the 'single seed and simple
      propagation' hypothesis). METHODS: Subjects included 36 patients with sporadic
      ALS and initial symptoms in the bulbar, respiratory or upper limb regions.
      Abnormal spontaneous activities in needle electromyography (nEMG)-that is,
      fibrillation potentials, positive sharp waves (Fib/PSWs) or fasciculation
      potentials (FPs)-were compared among the unilateral muscles innervated by
      different spinal segments, especially between the T10 and L5 paraspinal muscles,
      and between the vastus medialis and biceps femoris. Axon length and the
      proportion of muscle fibre types, which are both related to motoneuronal
      vulnerability in ALS, are similar in the paired muscles. RESULTS: Fourteen of 36
      patients showed a non-contiguous distribution of nEMG abnormalities from the
      onset site, with skipping of intermediate segments. In eight of them, the non
      contiguous pattern was evident between paired muscles with the same motoneuronal
      vulnerability. The non-contiguously affected lumbosacral lesions involved
      motoneuron columns horizontally or radially proximate to one another, appearing
      to form a cluster in four of the eight patients. FPs, known to precede Fib/PSWs,
      were shown more frequently than Fib/PSWs in all the lumbosacral segments but L5,
      suggesting that 2nd hits occur at L5 and then spread to other lumbosacral
      segments. CONCLUSIONS: In sporadic ALS, the distribution of lower motoneuron
      involvement cannot be explained by the 'single seed and simple propagation'
      hypothesis alone. We propose a 'multifocal hits and local propagation' hypothesis
      instead.

PMID- 24027299
TI  - Low-dose-rate radiation exposure leads to testicular damage with decreases in
      DNMT1 and HDAC1 in the murine testis.
AB  - This study examined the effects of continuous low-dose-rate radiation exposure
      (3.49 mGy/h) of gamma rays on mice testicles. C57BL/6 mice were divided into sham
      and radiation groups (n = 8 each), and were exposed to either sham irradiation or
      2 Gy for 21 days, 0.2 Gy for 2 days, or 0.02 Gy for 6 h of low-dose-rate
      irradiation. Testicular weight, seminiferous tubular diameter, and seminiferous
      epithelial depth were significantly decreased in the mice irradiated with 2 Gy at
      1 and 9 days after exposure. Moreover, the low-dose-rate radiation exposure
      induced an increase in malondialdehyde levels, and a decrease in superoxide
      dismutase activity in the testis of mice irradiated with 2 Gy at 1 and 9 days
      after exposure. The sperm count and motility in the epididymis also decreased in
      mice irradiated with 2 Gy at 1 and 9 days after exposure, whereas there was no
      significant effect on the proportion of abnormal sperm. The expressions of DNA
      methlytransferases-1 and histone deacetylases 1 in testes irradiated with 2 Gy
      were significantly decreased compared with the sham group. In conclusion, the
      damage exerted on the testes and epididymis largely depended on the total dose of
      low-dose-rate radiation. 

PMID- 24027300
TI  - Relative biological effectiveness of simulated solar particle event proton
      radiation to induce acute hematological change in the porcine model.
AB  - The present study was undertaken to determine relative biological effectiveness
      (RBE) values for simulated solar particle event (SPE) radiation on peripheral
      blood cells using Yucatan minipigs and electron-simulated SPE as the reference
      radiation. The results demonstrated a generally downward trend in the RBE values
      with increasing doses of simulated SPE radiation for leukocytes in the irradiated
      animals. The fitted RBE values for white blood cells (WBCs), lymphocytes,
      neutrophils, monocytes and eosinophils were above 1.0 in all three radiation dose
      groups at all time-points evaluated, and the lower limits of the 95% confidence
      intervals were > 1.0 in the majority of the dose groups at different time-points,
      which together suggest that proton-simulated SPE radiation is more effective than
      electron-simulated SPE radiation in reducing the number of peripheral WBCs,
      lymphocytes, neutrophils, monocytes and eosinophils, especially at the low end of
      the 5-10 Gy dose range evaluated. Other than the RBE values, the responses of
      leukocytes to electron-simulated SPE radiation and proton-simulated SPE radiation
      exposure are highly similar with respect to the time-course, the most
      radiosensitive cell type (the lymphocytes), and the shape of the dose-response
      curves, which is generally log-linear. These findings provide additional evidence
      that electron-simulated SPE radiation is an appropriate reference radiation for
      determination of RBE values for the simulated SPE radiations, and the RBE
      estimations using electron-simulated SPE radiation as the reference radiation are
      not complicated by other characteristics of the leukocyte response to radiation
      exposure. 

PMID- 24027302
TI  - Direct formation of vaccinia virus membranes from the endoplasmic reticulum in
      the absence of the newly characterized L2-interacting protein A30.5.
AB  - Crescents consisting of a single lipoprotein membrane with an external protein
      scaffold comprise the initial structural elements of poxvirus morphogenesis.
      Crescents enlarge to form spherical immature virions, which enclose viroplasm
      consisting of proteins destined to form the cores of mature virions. Previous
      studies suggest that the L2 protein participates in the recruitment of
      endoplasmic reticulum (ER)-derived membranes to form immature virions within
      assembly sites of cytoplasmic factories. Here we show that L2 interacts with the
      previously uncharacterized 42-amino-acid A30.5 protein. An open reading frame
      similar in size to the one encoding A30.5 is at the same genome location in
      representatives of all chordopoxvirus genera. A30.5 has a putative transmembrane
      domain and colocalized with markers of the endoplasmic reticulum and with L2. By
      constructing a complementing cell line expressing A30.5, we isolated a deletion
      mutant virus that exhibits a defect in morphogenesis in normal cells. Large
      electron-dense cytoplasmic inclusions and clusters of scaffold protein-coated
      membranes that resemble crescents and immature virions devoid of viroplasm were
      seen in place of normal structures. Crescent-shaped membranes were continuous
      with the endoplasmic reticulum membrane and oriented with the convex scaffold
      protein-coated side facing the lumen, while clusters of completed spherical
      immature-virion-like forms were trapped within the expanded lumen. Immature
      virion-like structures were more abundant in infected RK-13 cells than in BS-C-1
      or HeLa cells, in which cytoplasmic inclusions were decorated with scaffold
      protein-coated membrane arcs. We suggest that the outer surface of the poxvirus
      virion is derived from the luminal side of the ER membrane. 

PMID- 24027301
TI  - The perils of pathogen discovery: origin of a novel parvovirus-like hybrid genome
      traced to nucleic acid extraction spin columns.
AB  - Next-generation sequencing was used for discovery and de novo assembly of a
      novel, highly divergent DNA virus at the interface between the Parvoviridae and
      Circoviridae. The virus, provisionally named parvovirus-like hybrid virus (PHV),
      is nearly identical by sequence to another DNA virus, NIH-CQV, previously
      detected in Chinese patients with seronegative (non-A-E) hepatitis. Although we
      initially detected PHV in a wide range of clinical samples, with all strains
      sharing ~99% nucleotide and amino acid identity with each other and with NIH-CQV,
      the exact origin of the virus was eventually traced to contaminated silica
      binding spin columns used for nucleic acid extraction. Definitive confirmation of
      the origin of PHV, and presumably NIH-CQV, was obtained by in-depth analyses of
      water eluted through contaminated spin columns. Analysis of environmental
      metagenome libraries detected PHV sequences in coastal marine waters of North
      America, suggesting that a potential association between PHV and diatoms (algae)
      that generate the silica matrix used in the spin columns may have resulted in
      inadvertent viral contamination during manufacture. The confirmation of PHV/NIH
      CQV as laboratory reagent contaminants and not bona fide infectious agents of
      humans underscores the rigorous approach needed to establish the validity of new
      viral genomes discovered by next-generation sequencing. 

PMID- 24027303
TI  - Homologous recombination in E3 genes of human adenovirus species D.
AB  - Genes within the E3 transcription unit of human adenoviruses modulate host immune
      responses to infection. A comprehensive genomics and bioinformatics analysis of
      the E3 transcription unit for 38 viruses within human adenovirus species D (HAdV
      D) revealed distinct and surprising patterns of homologous recombination.
      Homologous recombination was identified in open reading frames for E3 CR1alpha,
      CR1beta, and CR1gamma, similar to that previously observed with genes encoding
      the three major structural capsid proteins, the penton base, hexon, and fiber. 

PMID- 24027304
TI  - Involvement of the rabies virus phosphoprotein gene in neuroinvasiveness.
AB  - Rabies virus (RABV), which is transmitted via a bite wound caused by a rabid
      animal, infects peripheral nerves and then spreads to the central nervous system
      (CNS) before causing severe neurological symptoms and death in the infected
      individual. Despite the importance of this ability of the virus to spread from a
      peripheral site to the CNS (neuroinvasiveness) in the pathogenesis of rabies,
      little is known about the mechanism underlying the neuroinvasiveness of RABV. In
      this study, to obtain insights into the mechanism, we conducted comparative
      analysis of two fixed RABV strains, Nishigahara and the derivative strain Ni-CE,
      which cause lethal and asymptomatic infections, respectively, in mice after
      intramuscular inoculation. Examination of a series of chimeric viruses harboring
      the respective genes from Nishigahara in the genetic background of Ni-CE revealed
      that the Nishigahara phosphoprotein (P) gene plays a major role in the
      neuroinvasiveness by mediating infection of peripheral nerves. The results
      obtained from both in vivo and in vitro experiments strongly suggested that the
      Nishigahara P gene, but not the Ni-CE P gene, is important for stable viral
      replication in muscle cells. Further investigation based on the previous finding
      that RABV phosphoprotein counteracts the host interferon (IFN) system
      demonstrated that the Nishigahara P gene, but not the Ni-CE P gene, functions to
      suppress expression of the beta interferon (IFN-beta) gene (Ifn-beta) and IFN
      stimulated genes in muscle cells. In conclusion, we provide the first data
      strongly suggesting that RABV phosphoprotein assists viral replication in muscle
      cells by counteracting the host IFN system and, consequently, enhances infection
      of peripheral nerves. 

PMID- 24027305
TI  - Dissociation of prion protein amyloid seeding from transmission of a spongiform
      encephalopathy.
AB  - Misfolding and aggregation of proteins are common pathogenic mechanisms of a
      group of diseases called proteinopathies. The formation and spread of
      proteinaceous lesions within and between individuals were first described in
      prion diseases and proposed as the basis of their infectious nature. Recently, a
      similar "prion-like" mechanism of transmission has been proposed in other
      neurodegenerative diseases such as Alzheimer's disease. We investigated if
      misfolding and aggregation of corrupted prion protein (PrP(TSE)) are always
      associated with horizontal transmission of disease. Knock-in transgenic mice
      (101LL) expressing mutant PrP (PrP-101L) that are susceptible to disease but do
      not develop any spontaneous neurological phenotype were inoculated with (i) brain
      extracts containing PrP(TSE) from healthy 101LL mice with PrP plaques in the
      corpus callosum or (ii) brain extracts from mice overexpressing PrP-101L with
      neurological disease, severe spongiform encephalopathy, and formation of
      proteinase K-resistant PrP(TSE). In all instances, 101LL mice developed PrP
      plaques in the area of inoculation and vicinity in the absence of clinical
      disease or spongiform degeneration of the brain. Importantly, 101LL mice did not
      transmit disease on serial passage, ruling out the presence of subclinical
      infection. Thus, in both experimental models the formation of PrP(TSE) is not
      infectious. These results have implications for the interpretation of tests based
      on the detection of protein aggregates and suggest that de novo formation of
      PrP(TSE) in the host does not always result in a transmissible prion disease. In
      addition, these results question the validity of assuming that all diseases due
      to protein misfolding can be transmitted between individuals. 

PMID- 24027306
TI  - The structure and host entry of an invertebrate parvovirus.
AB  - The 3.5-A resolution X-ray crystal structure of mature cricket parvovirus (Acheta
      domesticus densovirus [AdDNV]) has been determined. Structural comparisons show
      that vertebrate and invertebrate parvoviruses have evolved independently,
      although there are common structural features among all parvovirus capsid
      proteins. It was shown that raising the temperature of the AdDNV particles caused
      a loss of their genomes. The structure of these emptied particles was determined
      by cryo-electron microscopy to 5.5-A resolution, and the capsid structure was
      found to be the same as that for the full, mature virus except for the absence of
      the three ordered nucleotides observed in the crystal structure. The viral
      protein 1 (VP1) amino termini could be externalized without significant damage to
      the capsid. In vitro, this externalization of the VP1 amino termini is
      accompanied by the release of the viral genome. 

PMID- 24027307
TI  - Structure, adsorption to host, and infection mechanism of virulent lactococcal
      phage p2.
AB  - Lactococcal siphophages from the 936 and P335 groups infect the Gram-positive
      bacterium Lactococcus lactis using receptor binding proteins (RBPs) attached to
      their baseplate, a large multiprotein complex at the distal part of the tail. We
      have previously reported the crystal and electron microscopy (EM) structures of
      the baseplates of phages p2 (936 group) and TP901-1 (P335 group) as well as the
      full EM structure of the TP901-1 virion. Here, we report the complete EM
      structure of siphophage p2, including its capsid, connector complex, tail, and
      baseplate. Furthermore, we show that the p2 tail is characterized by the presence
      of protruding decorations, which are related to adhesins and are likely
      contributed by the major tail protein C-terminal domains. This feature is
      reminiscent of the tail of Escherichia coli phage lambda and Bacillus subtilis
      phage SPP1 and might point to a common mechanism for establishing initial
      interactions with their bacterial hosts. Comparative analyses showed that the
      architecture of the phage p2 baseplate differs largely from that of lactococcal
      phage TP901-1. We quantified the interaction of its RBP with the saccharidic
      receptor and determined that specificity is due to lower k(off) values of the
      RBP/saccharidic dissociation. Taken together, these results suggest that the
      infection of L. lactis strains by phage p2 is a multistep process that involves
      reversible attachment, followed by baseplate activation, specific attachment of
      the RBPs to the saccharidic receptor, and DNA ejection.

PMID- 24027309
TI  - Analysis of borna disease virus trafficking in live infected cells by using a
      virus encoding a tetracysteine-tagged p protein.
AB  - Borna disease virus (BDV) is a nonsegmented, negative-stranded RNA virus
      characterized by noncytolytic persistent infection and replication in the nuclei
      of infected cells. To gain further insight on the intracellular trafficking of
      BDV components during infection, we sought to generate recombinant BDV (rBDV)
      encoding fluorescent fusion viral proteins. We successfully rescued a virus
      bearing a tetracysteine tag fused to BDV-P protein, which allowed assessment of
      the intracellular distribution and dynamics of BDV using real-time live imaging.
      In persistently infected cells, viral nuclear inclusions, representing viral
      factories tethered to chromatin, appeared to be extremely static and stable,
      contrasting with a very rapid and active trafficking of BDV components in the
      cytoplasm. Photobleaching (fluorescence recovery after photobleaching [FRAP] and
      fluorescence loss in photobleaching [FLIP]) imaging approaches revealed that BDV
      components were permanently and actively exchanged between cellular compartments,
      including within viral inclusions, albeit with a fraction of BDV-P protein not
      mobile in these structures, presumably due to its association with viral and/or
      cellular proteins. We also obtained evidence for transfer of viral material
      between persistently infected cells, with routing of the transferred components
      toward the cell nucleus. Finally, coculture experiments with noninfected cells
      allowed visualization of cell-to-cell BDV transmission and movement of the
      incoming viral material toward the nucleus. Our data demonstrate the potential of
      tetracysteine-tagged recombinant BDV for virus tracking during infection, which
      may provide novel information on the BDV life cycle and on the modalities of its
      interaction with the nuclear environment during viral persistence. 

PMID- 24027310
TI  - Human H7N9 influenza A viruses replicate in swine respiratory tissue explants.
AB  - Recently, novel H7N9 influenza viruses have caused an unprecedented outbreak in
      humans. Pigs are an important intermediate host for influenza; thus, we assessed
      the replication ability of three human H7N9 viruses (A/Anhui/1/2013,
      A/Shanghai/1/2013, A/Shanghai/2/2013) in swine tissue explants. All viruses
      tested replicated efficiently in explants from tracheas and bronchi, with limited
      replication in alveolar cells. Swine respiratory tissue explants can serve as an
      efficient model for screening replication potential of newly emerging H7N9
      viruses. 

PMID- 24027308
TI  - Epstein-Barr virus induces global changes in cellular mRNA isoform usage that are
      important for the maintenance of latency.
AB  - Oncogenic viruses promote cell proliferation through the dramatic reorganization
      of host transcriptomes. In addition to regulating mRNA abundance, changes in mRNA
      isoform usage can have a profound impact on the protein output of the
      transcriptome. Using Epstein-Barr virus (EBV) transformation of primary B cells,
      we have studied the ability of an oncogenic virus to alter the mRNA isoform
      profile of its host. Using the algorithm called SplicerEX with two complementary
      Affymetrix microarray platforms, we uncovered 433 mRNA isoform changes regulated
      by EBV during B-cell transformation. These changes were largely orthogonal with
      the 2,163 mRNA abundance changes observed during transformation, such that less
      than one-third of mRNAs changing at the level of isoform also changed in overall
      abundance. While we observed no preference for a mechanistic class of mRNA
      isoform change, we detected a significant shortening of 3' untranslated regions
      and exclusion of cassette exons in EBV-transformed cells relative to uninfected B
      cells. Gene ontology analysis of the mRNA isoform changes revealed significant
      enrichment in nucleic acid binding proteins. We validated several of these
      isoform changes and were intrigued by those in two mRNAs encoding the proteins
      XBP1 and TCF4, which have both been shown to bind and activate the promoter of
      the major EBV lytic trans-activator BZLF1. Our studies indicate that EBV latent
      infection promotes the usage of mRNA isoforms of XBP1 and TCF4 that restrict
      BZLF1 activation. Therefore, characterization of global changes in mRNA isoform
      usage during EBV infection identifies a new mechanism for the maintenance of
      latent infection. 

PMID- 24027311
TI  - Influenza A virus proteins NS1 and hemagglutinin along with M2 are involved in
      stimulation of autophagy in infected cells.
AB  - The NS1 protein of influenza A virus is known to downregulate apoptosis early in
      infection in order to support virus replication (O. P. Zhirnov, T. E. Konakova,
      T. Wolff, and H. D. Klenk, J. Virol. 76:1617-1625, 2002). In the present study,
      we analyzed the development of autophagy, another mechanism to protect cells from
      degradation that depends on NS1 expression. To this end, we compared autophagy in
      cells infected with wild-type (WT) influenza virus and virus lacking the NS1 gene
      (delNS1 virus). The results show that in WT-infected cells but not in delNS1
      virus-infected cells, synthesis of the autophagy marker LC3-II, the lipidated
      form of microtubule light chain-associated protein LC3, is stimulated and that
      LC3-II accumulates in a perinuclear zone enriched with double-layered membrane
      vesicles characteristic of autophagosomes. Transfection experiments revealed that
      NS1 expressed alone was unable to upregulate autophagy, whereas hemagglutinin
      (HA) and M2 were. Proteolytic cleavage of HA increased autophagy. Taken together,
      these observations indicate that NS1 stimulates autophagy indirectly by
      upregulating the synthesis of HA and M2. Thus, it appears that NS1, besides
      downregulating apoptosis, is involved in upregulation of autophagy and that it
      supports the survival of infected cells by both mechanisms. 

PMID- 24027312
TI  - Characterization of a novel G3P[3] rotavirus isolated from a lesser horseshoe
      bat: a distant relative of feline/canine rotaviruses.
AB  - Bats are considered important animal reservoirs for many viruses pathogenic to
      humans. An approach based on viral metagenomics was used to study gut specimens
      from 78 insectivorous bats in Yunnan Province, China. Seventy-four reads were
      found to be related to group A rotavirus (RVA). Further reverse transcription-PCR
      screening and viral isolation on cell cultures confirmed the presence of a novel
      RVA strain, named RVA/Bat-tc/MSLH14/2012/G3P[3], in 1 (6%) of 16 lesser horseshoe
      bats. Full genomic sequencing analyses showed that MSLH14 possessed the genotype
      constellation G3-P[3]-I8-R3-C3-M3-A9-N3-T3-E3-H6, which is akin to human and
      animal rotaviruses believed to be of feline/canine origin. Phylogenetic analysis
      indicated that VP7 was most closely related to bovine RVA strains from India,
      whereas VP4 was most closely related to an unusual human RVA strain, CMH222, with
      animal characteristics isolated in Thailand. The remaining gene segments were
      only distantly related to a range of animal RVA strains, most of which are
      believed to be related to feline/canine RVAs. Experimental infection showed that
      bat RVA strain MSLH14 was highly pathogenic to suckling mice, causing 100%
      mortality when they were inoculated orally with a titer as low as 5 * 102 50%
      tissue culture infective doses. As this virus is not closely related to any known
      RVA strain, it is tempting to speculate that it is a true bat RVA strain rather
      than a virus transmitted between species. However, further screening of bat
      populations, preferably juvenile animals, will be crucial in determining whether
      or not this virus is widely distributed in the bat population.

PMID- 24027313
TI  - Human astrocytic cells support persistent coxsackievirus B3 infection.
AB  - Enteroviruses can frequently target the human central nervous system to induce a
      variety of neurological diseases. Although enteroviruses are highly cytolytic,
      emerging evidence has shown that these viruses can establish persistent
      infections both in vivo and in vitro. Here, we investigated the susceptibility of
      three human brain cell lines, CCF-STTG1, T98G, and SK-N-SH, to infection with
      three enterovirus serotypes: coxsackievirus B3 (CVB3), enterovirus 71, and
      coxsackievirus A9. Persistent infection was observed in CVB3-infected CCF-STTG1
      cells, as evidenced by prolonged detection of infectious virions, viral RNA, and
      viral antigens. Of note, infected CCF-STTG1 cells expressed the nonfunctional
      canonical viral receptors coxsackievirus-adenovirus receptor and decay
      accelerating factor, while removal of cell surface chondroitin sulfate from CCF
      STTG1 cells inhibited the replication of CVB3, suggesting that receptor usage was
      one of the major limiting factors in CVB3 persistence. In addition, CVB3
      curtailed the induction of beta interferon in infected CCF-STTG1 cells, which
      likely contributed to the initiation of persistence. Furthermore, proinflammatory
      chemokines and cytokines, such as vascular cell adhesion molecule 1, interleukin
      8 (IL-8), and IL-6, were upregulated in CVB3-infected CCF-STTG1 cells and human
      progenitor-derived astrocytes. Our data together demonstrate the potential of CCF
      STTG1 cells to be a novel cell model for studying CVB3-central nervous system
      interactions, providing the basis toward a better understanding of CVB3-induced
      chronic neuropathogenesis. 

PMID- 24027314
TI  - A direct and versatile assay measuring membrane penetration of adenovirus in
      single cells.
AB  - Endocytosis is the most prevalent entry port for viruses into cells, but viruses
      must escape from the lumen of endosomes to ensure that viral genomes reach a site
      for replication and progeny formation. Endosomal escape also helps viruses bypass
      endolysosomal degradation and presentation to certain Toll-like intrinsic
      immunity receptors. The mechanisms for cytosolic delivery of nonenveloped viruses
      or nucleocapsids from enveloped viruses are poorly understood, in part because no
      quantitative assays are readily available which directly measure the penetration
      of viruses into the cytosol. Following uptake by clathrin-mediated endocytosis or
      macropinocytosis, the nonenveloped adenoviruses penetrate from endosomes to the
      cytosol, and they traffic with cellular motors on microtubules to the nucleus for
      replication. In this report, we present a novel single-cell imaging assay which
      quantitatively measures individual cytosolic viruses and distinguishes them from
      endosomal viruses or viruses at the plasma membrane. Using this assay, we showed
      that the penetration of human adenoviruses of the species C and B occurs rapidly
      after virus uptake. Efficient penetration does not require acidic pH in
      endosomes. This assay is versatile and can be adapted to other adenoviruses and
      members of other nonenveloped and enveloped virus families. 

PMID- 24027316
TI  - A microRNA encoded by Autographa californica nucleopolyhedrovirus regulates
      expression of viral gene ODV-E25.
AB  - Baculovirus-encoded microRNAs (miRNAs) have been described in Bombyx mori
      nucleopolyhedrovirus; however, most of their functions remain unclear. Here we
      report the identification and characterization of an miRNA encoded by Autographa
      californica nucleopolyhedrovirus. The identified miRNA, AcMNPV-miR-1, perfectly
      matched a segment in the coding sequence of the viral gene ODV-E25 and
      downregulated ODV-E25 mRNA expression, which likely resulted in a reduction of
      infectious budded virions and accelerated the formation of occlusion-derived
      virions. 

PMID- 24027315
TI  - Evaluation of novel acyclic nucleoside phosphonates against human and animal
      gammaherpesviruses revealed an altered metabolism of cyclic prodrugs upon Epstein
      Barr virus reactivation in P3HR-1 cells.
AB  - Acyclic nucleoside phosphonates (ANPs), such as (S)-1-[(3-hydroxy-2
      phosphonomethoxy)propyl)]cytosine (HPMPC), are an important group of broad
      spectrum antiviral agents with activity against DNA viruses. In this report, we
      present the in vitro potencies of novel ANPs against gammaherpesviruses,
      including Kaposi's sarcoma-associated herpesvirus, Epstein-Barr virus (EBV), and
      three animal gammaherpesviruses. 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5
      azacytosine (HPMP-5-azaC), (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]-3
      deazaadenine (3-deaza-HPMPA), and their cyclic derivatives have emerged as highly
      potent antigammaherpesvirus agents. Interestingly, cyclic prodrugs of ANPs
      exhibited reduced activities against EBV strain P3HR-1, but not against EBV
      strain Akata. Cell culture metabolism studies with HPMPC and cyclic HPMPC
      revealed that these differences were attributable to an altered drug metabolism
      in P3HR-1 cells after EBV reactivation and, more specifically, to a reduced
      hydrolysis of cyclic HPMPC by cyclic CMP phosphodiesterase. We did not correlate
      this effect with phosphodiesterase downregulation, or to functional mutations.
      Instead, altered cyclic AMP levels in P3HR-1 cells indicated a competitive
      inhibition of the phosphodiesterase by this cyclic nucleotide. Finally, both
      HPMPC and HPMP-5-azaC emerged as highly effective inhibitors in vivo through
      significant inhibition of murine gammaherpesvirus replication and dissemination.
      With the current need for potent antigammaherpesvirus agents, our findings
      underline the requirement of appropriate surrogate viruses for antiviral
      susceptibility testing and highlight HPMP-5-azaC as a promising compound for
      future clinical development. 

PMID- 24027318
TI  - Chandipura virus induces neuronal death through Fas-mediated extrinsic apoptotic
      pathway.
AB  - Chandipura virus (CHPV; genus Vesiculovirus, family Rhabdoviridae) is an emerging
      tropical pathogen with a case fatality rate of 55 to 75% that predominantly
      affects children in the age group of 2 to 16 years. Although it has been
      established as a neurotropic virus causing encephalitis, the molecular pathology
      leading to neuronal death is unknown. The present study elucidates for the first
      time the mechanism of cell death in neurons after CHPV infection that answers the
      basic cause of CHPV-mediated neurodegeneration. Through various cell death assays
      in vitro and in vivo, a relationship between viral replication within neuron and
      neuronal apoptosis has been established. We report that expression of CHPV
      phosphoprotein increases up to 6 h postinfection and diminishes thereafter in
      neuronal cell lines, signifying the replicative phase of CHPV. Various analyses
      conducted during the investigation established that CHPV-infected neurons are
      undergoing apoptosis through an extrinsic pathway mediated through the Fas
      associated death domain (FADD) following activation of caspase-8 and -3 and
      prominent cleavage of poly(ADP-ribose) polymerase (PARP). Knocking down the
      expression of caspase-3, the final executioner of apoptosis, in a neuronal cell
      line by endoribonuclease-prepared small interfering RNA (siRNA) validated its
      pivotal role in CHPV-mediated neurodegeneration by showing reduction in apoptosis
      after CHPV infection. 

PMID- 24027319
TI  - Dynamic viral dissemination in mice infected with yellow fever virus strain 17D.
AB  - Arboviruses such as yellow fever virus (YFV) are transmitted between arthropod
      vectors and vertebrate hosts. While barriers limiting arbovirus population
      diversity have been observed in mosquitoes, whether barriers exist in vertebrate
      hosts is unclear. To investigate whether arboviruses encounter bottlenecks during
      dissemination in the vertebrate host, we infected immunocompetent mice and immune
      deficient mice lacking alpha/beta interferon (IFN-alpha/beta) receptors (IFNAR-/-
      mice) with a pool of genetically marked viruses to evaluate dissemination and
      host barriers. We used the live attenuated vaccine strain YFV-17D, which contains
      many mutations compared with virulent YFV. We found that intramuscularly injected
      immunocompetent mice did not develop disease and that viral dissemination was
      restricted. Conversely, 32% of intramuscularly injected IFNAR-/- mice developed
      disease. By following the genetically marked viruses over time, we found broad
      dissemination in IFNAR-/- mice followed by clearance. The patterns of viral
      dissemination were similar in mice that developed disease and mice that did not
      develop disease. Unlike our previous results with poliovirus, these results
      suggest that YFV-17D encounters no major barriers during dissemination within a
      vertebrate host in the absence of the type I IFN response.

PMID- 24027317
TI  - Kaposi's sarcoma-associated herpesvirus K7 modulates Rubicon-mediated inhibition
      of autophagosome maturation.
AB  - Autophagy is an important innate safeguard mechanism for protecting an organism
      against invasion by pathogens. We have previously discovered that Kaposi's
      sarcoma-associated herpesvirus (KSHV) evades this host defense through tight
      suppression of autophagy by targeting multiple steps of autophagy signal
      transduction. Here, we report that KSHV K7 protein interacts with Rubicon
      autophagy protein and inhibits the autophagosome maturation step by blocking
      Vps34 enzymatic activity, further highlighting how KSHV deregulates autophagy
      mediated host immunity for its life cycle. 

PMID- 24027320
TI  - Middle East respiratory syndrome coronavirus accessory protein 4a is a type I
      interferon antagonist.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe acute
      respiratory infection with as yet unclear epidemiology. We previously showed that
      MERS-CoV counteracts parts of the innate immune response in human bronchiolar
      cells. Here we analyzed accessory proteins 3, 4a, 4b, and 5 for their abilities
      to inhibit the type I interferon response. Accessory protein 4a was found to
      block interferon induction at the level of melanoma differentiation-associated
      protein 5 (MDA5) activation presumably by direct interaction with double-stranded
      RNA. 

PMID- 24027321
TI  - Antibody recognition of the pandemic H1N1 Influenza virus hemagglutinin receptor
      binding site.
AB  - Influenza virus is a global health concern due to its unpredictable pandemic
      potential. This potential threat was realized in 2009 when an H1N1 virus emerged
      that resembled the 1918 virus in antigenicity but fortunately was not nearly as
      deadly. 5J8 is a human antibody that potently neutralizes a broad spectrum of
      H1N1 viruses, including the 1918 and 2009 pandemic viruses. Here, we present the
      crystal structure of 5J8 Fab in complex with a bacterially expressed and refolded
      globular head domain from the hemagglutinin (HA) of the A/California/07/2009
      (H1N1) pandemic virus. 5J8 recognizes a conserved epitope in and around the
      receptor binding site (RBS), and its HCDR3 closely mimics interactions of the
      sialic acid receptor. Electron microscopy (EM) reconstructions of 5J8 Fab in
      complex with an HA trimer from a 1986 H1 strain and with an engineered stabilized
      HA trimer from the 2009 H1 pandemic virus showed a similar mode of binding. As
      for other characterized RBS-targeted antibodies, 5J8 uses avidity to extend its
      breadth and affinity against divergent H1 strains. 5J8 selectively interacts with
      HA insertion residue 133a, which is conserved in pandemic H1 strains and has
      precluded binding of other RBS-targeted antibodies. Thus, the RBS of divergent
      HAs is targeted by 5J8 and adds to the growing arsenal of common recognition
      motifs for design of therapeutics and vaccines. Moreover, consistent with
      previous studies, the bacterially expressed H1 HA properly refolds, retaining its
      antigenic structure, and presents a low-cost and rapid alternative for
      engineering and manufacturing candidate flu vaccines. 

PMID- 24027322
TI  - Differing epidemiological dynamics of influenza B virus lineages in Guangzhou,
      southern China, 2009-2010.
AB  - The epidemiological and evolutionary dynamics of the two cocirculating lineages
      of influenza B virus, Victoria and Yamagata, are poorly understood, especially in
      tropical or subtropical areas of Southeast Asia. We performed a phylogenetic
      analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of influenza
      B viruses isolated in Guangzhou, a southern Chinese city, during 2009 to 2010 and
      compared the demographic and clinical features of infected patients. We
      identified multiple viral introductions of Victoria strains from both Chinese and
      international sources, which formed two phylogenetically and antigenically
      distinct clades (Victoria 1 and 2), some of which persisted between seasons. We
      identified one dominant Yamagata introduction from outside China during 2009. Our
      phylogenetic analysis reveals the occurrence of reassortment events among the
      Victoria and Yamagata lineages and also within the Victoria lineage. We found no
      significant difference in clinical severity by influenza B lineage, with the
      exceptions that (i) the Yamagata lineage infected older people than either
      Victoria lineage and (ii) fewer upper respiratory tract infections were caused by
      the Victoria 2 than the Victoria 1 clade. Overall, our study reveals the complex
      epidemiological dynamics of different influenza B lineages within a single
      geographic locality and has implications for vaccination policy in southern
      China. 

PMID- 24027323
TI  - Nucleolin interacts with the dengue virus capsid protein and plays a role in
      formation of infectious virus particles.
AB  - Dengue virus (DENV) is a mosquito-transmitted flavivirus that can cause severe
      disease in humans and is considered a reemerging pathogen of significant
      importance to public health. The DENV capsid (C) protein functions as a
      structural component of the infectious virion; however, it may have additional
      functions in the virus replicative cycle. Here, we show that the DENV C protein
      interacts and colocalizes with the multifunctional host protein nucleolin (NCL).
      Furthermore, we demonstrate that this interaction can be disrupted by the
      addition of an NCL binding aptamer (AS1411). Knockdown of NCL with small
      interfering RNA (siRNA) or treatment of cells with AS1411 results in a
      significant reduction of viral titers after DENV infection. Western blotting and
      quantitative RT-PCR (qRT-PCR) analysis revealed no differences in viral RNA or
      protein levels at early time points postinfection, suggesting a role for NCL in
      viral morphogenesis. We support this hypothesis by showing that treatment with
      AS1411 alters the migration characteristics of the viral capsid, as visualized by
      native electrophoresis. Here, we identify a critical interaction between DENV C
      protein and NCL that represents a potential new target for the development of
      antiviral therapeutics. 

PMID- 24027324
TI  - An amino acid of human parainfluenza virus type 3 nucleoprotein is critical for
      template function and cytoplasmic inclusion body formation.
AB  - The nucleoprotein (N) and phosphoprotein (P) interaction of nonsegmented negative
      strand RNA viruses is essential for viral replication; this includes N0-P (N0,
      free of RNA) interaction and the interaction of N-RNA with P. The precise site(s)
      within N that mediates the N-P interaction and the detailed regulating mechanism,
      however, are less clear. Using a human parainfluenza virus type 3 (HPIV3)
      minigenome assay, we found that an N mutant (N(L478A) did not support reporter
      gene expression. Using in vivo and in vitro coimmunoprecipitation, we found that
      N(L478A) maintains the ability to form N(L478A)0-P, to self-assemble, and to form
      N(L478A)-RNA but that N(L478A)-RNA does not interact with P. Using an
      immunofluorescence assay, we found that N-P interaction provides the minimal
      requirement for the formation of cytoplasmic inclusion bodies, which contain
      viral RNA, N, P, and polymerase in HPIV3-infected cells. N(L478A) was unable to
      form inclusion bodies when coexpressed with P, but the presence of N rescued the
      ability of N(L478A) to form inclusion bodies and the transcriptional function of
      N(L478A), thereby suggesting that hetero-oligomers formed by N and N(L478A) are
      functional and competent to form inclusion bodies. Furthermore, we found that
      N(L478A) is also defective in virus growth. To our knowledge, we are the first to
      use a paramyxovirus to identify a precise amino acid within N that is critical
      for N-RNA and P interaction but not for N(0)-P interaction for the formation of
      inclusion bodies, which appear to be bona fide sites of RNA synthesis.

PMID- 24027325
TI  - Structural analysis of the hemagglutinin from the recent 2013 H7N9 influenza
      virus.
AB  - In March 2013, the Chinese Center for Disease Control and Prevention reported
      human infections with an H7N9 influenza virus, and by 20 July 2013, the numbers
      of laboratory-confirmed cases had climbed to 134, including 43 fatalities and 127
      hospitalizations. The newly emerging H7N9 viruses constitute an obvious public
      health concern because of the apparent severity of this outbreak. Here we focus
      on the hemagglutinins (HAs) of these viruses and assess their receptor binding
      phenotype in relation to previous HAs studied. Glycan microarray and kinetic
      analyses of recombinant A(H7N9) HAs were performed to compare the receptor
      binding profile of wild-type receptor binding site variants at position 217, a
      residue analogous to one of two positions known to switch avian to human receptor
      preference in H2N2 and H3N2 viruses. Two recombinant A(H7N9) HAs were
      structurally characterized, and a mutational study of the receptor binding site
      was performed to analyze important residues that can affect receptor preference
      and affinity. Results highlight a weak human receptor preference of the H7N9 HAs,
      suggesting that these viruses require further adaptation in order to adapt fully
      to humans. 

PMID- 24027326
TI  - Densovirus crosses the insect midgut by transcytosis and disturbs the epithelial
      barrier function.
AB  - Densoviruses are parvoviruses that can be lethal for insects of different orders
      at larval stages. Although the horizontal transmission mechanisms are poorly
      known, densoviral pathogenesis usually starts with the ingestion of contaminated
      food by the host. Depending on the virus, this leads to replication restricted to
      the midgut or excluding it. In both cases the success of infection depends on the
      virus capacity to enter the intestinal epithelium. Using the Junonia coenia
      densovirus (JcDNV) as the prototype virus and the lepidopteran host Spodoptera
      frugiperda as an interaction model, we focused on the early mechanisms of
      infection during which JcDNV crosses the intestinal epithelium to reach and
      replicate in underlying target tissues. We studied the kinetics of interaction of
      JcDNV with the midgut epithelium and the transport mechanisms involved. Using
      several approaches, in vivo, ex vivo, and in vitro, at molecular and cellular
      levels, we show that JcDNV is specifically internalized by endocytosis in
      absorptive cells and then crosses the epithelium by transcytosis. As a
      consequence, viral entry disturbs the midgut function. Finally, we showed that
      four mutations on the capsid of JcDNV affect specific recognition by the
      epithelial cells but not their binding. 

PMID- 24027327
TI  - Seminal plasma and semen amyloids enhance cytomegalovirus infection in cell
      culture.
AB  - Among the modes of transmission available to the cytomegalovirus (CMV) is sexual
      transmission, primarily via semen. Both male-to-female (M-F) and male-to-male (M
      M) sexual transmission significantly contribute toward the spread of CMV
      infections in the global population. Semen plays an important role in carrying
      the viral particle that invades the vaginal or rectal mucosa, thereby initiating
      viral replication. Both semen and seminal plasma (SP) can enhance HIV-1 infection
      in cell culture, and two amyloid fibrils, semen-derived enhancer of viral
      infection (SEVI) and amyloids derived from the semenogelins (SEM amyloids), have
      been identified as seminal factors sufficient to enhance HIV-1 infection (J.
      Munch et al., Cell 131:1059-1071, 2007; N. R. Roan et al., Cell Host Microbe
      10:541-550, 2011; F. Arnold et al., J. Virol. 86:1244-1249, 2012). Whether SP,
      SEVI, or SEM amyloids can enhance other viral infections has not been extensively
      examined. In this study, we found that SP, SEVI, and SEM amyloids strongly
      enhance both human CMV (HCMV) and murine CMV infection in cell culture. SEVI and
      SEM amyloids increased infection rates by >10-fold, as determined by both flow
      cytometry and fluorescence microscopy. Viral replication was increased by 50- to
      100-fold. Moreover, viral growth curve assays showed that SP, SEVI, and SEM
      amyloids sped up the kinetics of CMV replication such that the virus reached its
      replicative peak more quickly. Finally, we discovered that SEM amyloids and SEVI
      counteracted the effect of anti-gH in protecting against CMV infection.
      Collectively, the data suggest that semen enhances CMV infection through
      interactions between semen amyloid fibrils and viral particles, and these
      interactions may prevent HCMV from being neutralized by anti-gH antibody. 

PMID- 24027328
TI  - Baculovirus F-box protein LEF-7 modifies the host DNA damage response to enhance
      virus multiplication.
AB  - The DNA damage response (DDR) of a host organism represents an effective
      antiviral defense that is frequently manipulated and exploited by viruses to
      promote multiplication. We report here that the large DNA baculoviruses, which
      require host DDR activation for optimal replication, encode a conserved
      replication factor, LEF-7, that manipulates the DDR via a novel mechanism. LEF-7
      suppresses DDR-induced accumulation of phosphorylated host histone variant H2AX
      (gamma-H2AX), a critical regulator of the DDR. LEF-7 was necessary and sufficient
      to block gamma-H2AX accumulation caused by baculovirus infection or DNA damage
      induced by means of pharmacological agents. Deletion of LEF-7 from the
      baculovirus genome allowed gamma-H2AX accumulation during virus DNA synthesis and
      impaired both very late viral gene expression and production of infectious
      progeny. Thus, LEF-7 is essential for efficient baculovirus replication. We
      determined that LEF-7 is a nuclear F-box protein that interacts with host S-phase
      kinase-associated protein 1 (SKP1), suggesting that LEF-7 acts as a substrate
      recognition component of SKP1/Cullin/F-box (SCF) complexes for targeted protein
      polyubiquitination. Site-directed mutagenesis demonstrated that LEF-7's N
      terminal F-box is necessary for gamma-H2AX repression and Autographa californica
      multiple nucleopolyhedrovirus (AcMNPV) replication events. We concluded that LEF
      7 expedites virus replication most likely by selective manipulation of one or
      more host factors regulating the DDR, including gamma-H2AX. Thus, our findings
      indicate that baculoviruses utilize a unique strategy among viruses for hijacking
      the host DDR by using a newly recognized F-box protein. 

PMID- 24027329
TI  - White spot syndrome virus IE1 and WSV056 modulate the G1/S transition by binding
      to the host retinoblastoma protein.
AB  - DNA viruses often target cellular proteins to modulate host cell cycles and
      facilitate viral genome replication. However, whether proliferation of white spot
      syndrome virus (WSSV) requires regulation of the host cell cycle remains unclear.
      In the present study, we show that two WSSV paralogs, IE1 and WSV056, can
      interact with Litopenaeus vannamei retinoblastoma (Rb)-like protein (lv-RBL)
      through the conserved LxCxE motif. Further investigation revealed that IE1 and
      WSV056 could also bind to Drosophila retinoblastoma family protein 1 (RBF1) in a
      manner similar to how they bind to lv-RBL. Using the Drosophila RBF-E2F pathway
      as a model system, we demonstrated that both IE1 and WSV056 could sequester RBF1
      from Drosophila E2F transcription factor 1 (E2F1) and subsequently activate E2F1
      to stimulate the G1/S transition. Our findings provide the first evidence that
      WSSV may regulate cell cycle progression by targeting the Rb-E2F pathway. 

PMID- 24027330
TI  - Mechanistic insights into the enhancement of adeno-associated virus transduction
      by proteasome inhibitors.
AB  - Proteasome inhibitors (e.g., bortezomib, MG132) are known to enhance adeno
      associated virus (AAV) transduction; however, whether this results from
      pleotropic proteasome inhibition or off-target serine and/or cysteine protease
      inhibition remains unresolved. Here, we examined recombinant AAV (rAAV) effects
      of a new proteasome inhibitor, carfilzomib, which specifically inhibits
      chymotrypsin-like proteasome activity and no other proteases. We determined that
      proteasome inhibitors act on rAAV through proteasome inhibition and not serine or
      cysteine protease inhibition, likely through positive changes late in
      transduction. 

PMID- 24027331
TI  - High-avidity and potently neutralizing cross-reactive human monoclonal antibodies
      derived from secondary dengue virus infection.
AB  - The envelope (E) protein of dengue virus (DENV) is the major target of
      neutralizing antibodies (Abs) and vaccine development. Previous studies of human
      dengue-immune sera reported that a significant proportion of anti-E Abs, known as
      group-reactive (GR) Abs, were cross-reactive to all four DENV serotypes and to
      one or more other flaviviruses. Based on studies of mouse anti-E monoclonal
      antibodies (MAbs), GR MAbs were nonneutralizing or weakly neutralizing compared
      with type-specific MAbs; a GR response was thus not regarded as important for
      vaccine strategy. We investigated the epitopes, binding avidities, and
      neutralization potencies of 32 human GR anti-E MAbs. In addition to fusion loop
      (FL) residues in E protein domain II, human GR MAbs recognized an epitope
      involving both FL and bc loop residues in domain II. The neutralization potencies
      and binding avidities of GR MAbs derived from secondary DENV infection were
      stronger than those derived from primary infection. GR MAbs derived from primary
      DENV infection primarily blocked attachment, whereas those derived from secondary
      infection blocked DENV postattachment. Analysis of the repertoire of anti-E MAbs
      derived from patients with primary DENV infection revealed that the majority were
      GR, low-avidity, and weakly neutralizing MAbs, whereas those from secondary
      infection were primarily GR, high-avidity, and potently neutralizing MAbs. Our
      findings suggest that the weakly neutralizing GR anti-E Abs generated from
      primary DENV infection become potently neutralizing MAbs against the four
      serotypes after secondary infection. The observation that the dengue immune
      status of the host affects the quality of the cross-reactive Abs generated has
      implications for new strategies for DENV vaccination. 

PMID- 24027332
TI  - Middle East respiratory syndrome coronavirus infection mediated by the
      transmembrane serine protease TMPRSS2.
AB  - The Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes host
      proteases for virus entry into lung cells. In the current study, Vero cells
      constitutively expressing type II transmembrane serine protease (Vero-TMPRSS2
      cells) showed larger syncytia at 18 h after infection with MERS-CoV than after
      infection with other coronaviruses. Furthermore, the susceptibility of Vero
      TMPRSS2 cells to MERS-CoV was 100-fold higher than that of non-TMPRSS2-expressing
      parental Vero cells. The serine protease inhibitor camostat, which inhibits
      TMPRSS2 activity, completely blocked syncytium formation but only partially
      blocked virus entry into Vero-TMPRSS2 cells. Importantly, the coronavirus is
      thought to enter cells via two distinct pathways, one mediated by TMPRSS2 at the
      cell surface and the other mediated by cathepsin L in the endosome. Simultaneous
      treatment with inhibitors of cathepsin L and TMPRSS2 completely blocked virus
      entry into Vero-TMPRSS2 cells, indicating that MERS-CoV employs both the cell
      surface and the endosomal pathway to infect Vero-TMPRSS2 cells. In contrast, a
      single camostat treatment suppressed MERS-CoV entry into human bronchial
      submucosal gland-derived Calu-3 cells by 10-fold and virus growth by 270-fold,
      although treatment with both camostat and (23,25)-trans-epoxysuccinyl-L
      leucylamindo-3-methylbutane ethyl ester, a cathepsin inhibitor, or treatment with
      leupeptin, an inhibitor of cysteine, serine, and threonine peptidases, was no
      more efficacious than treatment with camostat alone. Further, these inhibitors
      were not efficacious against MERS-CoV infection of MRC-5 and WI-38 cells, which
      were derived from lung, but these characters differed from those of mature
      pneumocytes. These results suggest that a single treatment with camostat is
      sufficient to block MERS-CoV entry into a well-differentiated lung-derived cell
      line.

PMID- 24027333
TI  - A mutant influenza virus that uses an N1 neuraminidase as the receptor-binding
      protein.
AB  - In the vast majority of influenza A viruses characterized to date, hemagglutinin
      (HA) is the receptor-binding and fusion protein, whereas neuraminidase (NA) is a
      receptor-cleaving protein that facilitates viral release but is expendable for
      entry. However, the NAs of some recent human H3N2 isolates have acquired receptor
      binding activity via the mutation D151G, although these isolates also appear to
      retain the ability to bind receptors via HA. We report here the laboratory
      generation of a mutation (G147R) that enables an N1 NA to completely co-opt the
      receptor-binding function normally performed by HA. Viruses with this mutant NA
      grow to high titers even in the presence of extensive mutations to conserved
      residues in HA's receptor-binding pocket. When the receptor-binding NA is paired
      with this binding-deficient HA, viral infectivity and red blood cell
      agglutination are blocked by NA inhibitors. Furthermore, virus-like particles
      expressing only the receptor-binding NA agglutinate red blood cells in an NA
      dependent manner. Although the G147R NA receptor-binding mutant virus that we
      characterize is a laboratory creation, this same mutation is found in several
      natural clusters of H1N1 and H5N1 viruses. Our results demonstrate that, at least
      in tissue culture, influenza virus receptor-binding activity can be entirely
      shifted from HA to NA. 

PMID- 24027334
TI  - Gamma interferon regulates contraction of the influenza virus-specific CD8 T cell
      response and limits the size of the memory population.
AB  - The factors that regulate the contraction of the CD8 T cell response and the
      magnitude of the memory cell population against localized mucosal infections such
      as influenza are important for generation of efficient vaccines but are currently
      undefined. In this study, we used a mouse model of influenza to demonstrate that
      the absence of gamma interferon (IFN-gamma) or IFN-gamma receptor 1 (IFN-gammaR1)
      leads to aberrant contraction of antigen-specific CD8 T cell responses. The
      increased accumulation of the effector CD8 T cell population was independent of
      viral load. Reduced contraction was associated with an increased fraction of CD8
      T cells expressing the interleukin-7 receptor (IL-7R) at the peak of the
      response, resulting in enhanced numbers of memory/memory precursor cells in IFN
      gamma(-/-) and IFN-gammaR(-/-) compared to wild-type (WT) mice. Blockade of IL-7
      within the lungs of IFN-gamma(-/-) mice restored the contraction of influenza
      virus-specific CD8 T cells, indicating that IL-7R is important for survival and
      is not simply a consequence of the lack of IFN-gamma signaling. Finally, enhanced
      CD8 T cell recall responses and accelerated viral clearance were observed in the
      IFN-gamma(-/-) and IFN-gammaR(-/-) mice after rechallenge with a heterologous
      strain of influenza virus, confirming that higher frequencies of memory
      precursors are formed in the absence of IFN-gamma signaling. In summary, we have
      identified IFN-gamma as an important regulator of localized viral immunity that
      promotes the contraction of antigen-specific CD8 T cells and inhibits memory
      precursor formation, thereby limiting the size of the memory cell population
      after an influenza virus infection. 

PMID- 24027335
TI  - Chimeric exchange of coronavirus nsp5 proteases (3CLpro) identifies common and
      divergent regulatory determinants of protease activity.
AB  - Human coronaviruses (CoVs) such as severe acute respiratory syndrome CoV (SARS
      CoV) and Middle East respiratory syndrome CoV (MERS-CoV) cause epidemics of
      severe human respiratory disease. A conserved step of CoV replication is the
      translation and processing of replicase polyproteins containing 16 nonstructural
      protein domains (nsp's 1 to 16). The CoV nsp5 protease (3CLpro; Mpro) processes
      nsp's at 11 cleavage sites and is essential for virus replication. CoV nsp5 has a
      conserved 3-domain structure and catalytic residues. However, the intra- and
      intermolecular determinants of nsp5 activity and their conservation across
      divergent CoVs are unknown, in part due to challenges in cultivating many human
      and zoonotic CoVs. To test for conservation of nsp5 structure-function
      determinants, we engineered chimeric betacoronavirus murine hepatitis virus (MHV)
      genomes encoding nsp5 proteases of human and bat alphacoronaviruses and
      betacoronaviruses. Exchange of nsp5 proteases from HCoV-HKU1 and HCoV-OC43, which
      share the same genogroup, genogroup 2a, with MHV, allowed for immediate viral
      recovery with efficient replication albeit with impaired fitness in direct
      competition with wild-type MHV. Introduction of MHV nsp5 temperature-sensitive
      mutations into chimeric HKU1 and OC43 nsp5 proteases resulted in clear
      differences in viability and temperature-sensitive phenotypes compared with MHV
      nsp5. These data indicate tight genetic linkage and coevolution between nsp5
      protease and the genomic background and identify differences in intramolecular
      networks regulating nsp5 function. Our results also provide evidence that
      chimeric viruses within coronavirus genogroups can be used to test nsp5
      determinants of function and inhibition in common isogenic backgrounds and cell
      types. 

PMID- 24027336
TI  - A single amino acid mutation in the envelope cytoplasmic tail restores the
      ability of an attenuated simian immunodeficiency virus mutant to deplete mucosal
      CD4+ T cells.
AB  - Disruption of the conserved motif GYxxO in the simian immunodeficiency virus
      (SIV) SIVmac239 envelope (Env) cytoplasmic tail resulted in a virus (DeltaGY)
      that exhibited a high plasma peak but uniquely failed to acutely deplete mucosal
      CD4(+) T cells. Here, we show that DeltaGY containing a flanking S727P mutation
      that was acquired in DeltaGY-infected macaques reacquired the ability to rapidly
      deplete CD4(+) T cells in lamina propria. This suggests that the GYxxO motif and
      S727P each contribute to SIV's targeting to mucosal tissues. 

PMID- 24027337
TI  - Identification of novel host factors via conserved domain search: Cns1
      cochaperone is a novel restriction factor of tombusvirus replication in yeast.
AB  - A large number of host-encoded proteins affect the replication of plus-stranded
      RNA viruses by acting as susceptibility factors. Many other cellular proteins are
      known to function as restriction factors of viral infections. Previous studies
      with tomato bushy stunt tombusvirus (TBSV) in a yeast model host have revealed
      the inhibitory function of TPR (tetratricopeptide repeat) domain-containing
      cyclophilins, which are members of the large family of host prolyl isomerases, in
      TBSV replication. In this paper, we tested additional TPR-containing yeast
      proteins in a cell-free TBSV replication assay and identified the Cns1p
      cochaperone for heat shock protein 70 (Hsp70) and Hsp90 chaperones as a strong
      inhibitor of TBSV replication. Cns1p interacted with the viral replication
      proteins and inhibited the assembly of the viral replicase complex and viral RNA
      synthesis in vitro. Overexpression of Cns1p inhibited TBSV replication in yeast.
      The use of a temperature-sensitive (TS) mutant of Cns1p in yeast revealed that at
      a semipermissive temperature, TS Cns1p could not inhibit TBSV replication.
      Interestingly, Cns1p and the TPR-containing Cpr7p cyclophilin have similar
      inhibitory functions during TBSV replication, although some of the details of
      their viral restriction mechanisms are different. Our observations indicate that
      TPR-containing cellular proteins could act as virus restriction factors. 

PMID- 24027341
TI  - Smells familiar: group-joining decisions of predatory mites are mediated by
      olfactory cues of social familiarity.
AB  - Group-living animals frequently have to trade off the costs and benefits of
      leaving an established group and joining another group. Owing to their high
      fitness relevance, group-joining decisions are commonly nonrandom and may be
      based on traits of both individual members and the group such as life stage, body
      size, social status and group density or size, respectively. Many group-living
      animals are able to recognize and to associate preferentially with familiar
      individuals, i.e. those encountered before. Hence, after dispersing from
      established groups, animals commonly have to decide whether to join a new
      familiar or unfamiliar group. Using binary choice situations we assessed the
      effects of social familiarity on group-joining behaviour of the plant-inhabiting
      predatory mite Phytoseiulus persimilis. Group living in P. persimilis is brought
      about by the patchy distribution of its spider mite prey and mutual conspecific
      attraction. In the first experiment, gravid predator females given a choice
      between spider mite patches occupied by unfamiliar and familiar groups of females
      strongly preferred to join familiar groups and to deposit their eggs in these
      patches. Preference for socially familiar groups was robust across biases of
      spider mite prey densities between choice options. The second experiment revealed
      that the predatory mite females can smell social familiarity from a distance.
      Females subjected to odour choice situations in artificial cages were more
      strongly attracted to the odour of familiar than unfamiliar groups. We argue that
      P. persimilis females preferentially join socially familiar groups because a
      familiar social environment relaxes competition and optimizes foraging and
      reproduction.

PMID- 24027338
TI  - Stress-induced cellular transcription factors expressed in trigeminal ganglionic
      neurons stimulate the herpes simplex virus 1 ICP0 promoter.
AB  - Alphaherpesvirinae family members can reactivate from latency following stress.
      The synthetic corticosteroid dexamethasone induces certain cellular transcription
      factors in murine and bovine trigeminal ganglionic neurons. Three dexamethasone
      induced transcription factors, Kruppel-like factor 15, Slug, and SPDEF,
      stimulated the herpes simplex virus type 1-infected cell protein 0 (ICP0)
      promoter more than 150-fold. Conversely, other viral promoters (VP16 and ICP4)
      were not strongly stimulated, suggesting that the ICP0 promoter is preferentially
      activated by dexamethasone-simulated stress. 

PMID- 24027342
TI  - Faecal avoidance and selective foraging: do wild mice have the luxury to avoid
      faeces?
AB  - Host-parasite interactions are a key determinant of the population dynamics of
      wild animals, and behaviours that reduce parasite transmission and infection may
      be important for improving host fitness. While antiparasite behaviours have been
      demonstrated in laboratory animals and domesticated ungulates, whether these
      behaviours operate in the wild is poorly understood. Therefore, examining
      antiparasite behaviours in natural populations is crucial for understanding their
      ecological significance. In this study, we examined whether two wild rodents
      (white-footed mice, Peromyscus leucopus, and deer mice, Peromyscus maniculatus),
      selectively foraged away from conspecific faeces or avoided faeces altogether,
      and whether faecal gastrointestinal parasite status affected their behaviour. We
      also tested whether wild mice, when nesting, avoided using material that had
      previously been used by healthy or parasite-infected conspecifics. Our results,
      in contrast to laboratory mouse studies, suggest that wild mice do not
      demonstrate faecal avoidance, selective foraging or selective use of nesting
      material; they preferred being near faeces and did not differentiate between
      faeces from parasitized and uninfected conspecifics. Behavioural avoidance to
      reduce parasite infection may still represent an important strategy; however,
      mice in our study population appeared to favour the opportunity to feed and nest
      over the risks of coming into contact with faecal-transmitted parasites.
      Furthermore, the presence of conspecific faeces may actually provide a positive
      cue of a good foraging or nesting location. Ultimately, balancing the trade-off
      of performing antiparasite behaviours to reduce infection with missing an
      important feeding or nesting opportunity may be very different for animals in the
      wild facing complex and stochastic environments.

PMID- 24027343
TI  - Responses of chimpanzees to cues of conspecific observation.
AB  - Recent evidence has shown that humans are remarkably sensitive to artificial cues
      of conspecific observation when making decisions with potential social
      consequences. Whether similar effects are found in other great apes has not yet
      been investigated. We carried out two experiments in which individual
      chimpanzees, Pan troglodytes, took items of food from an array in the presence of
      either an image of a large conspecific face or a scrambled control image. In
      experiment 1 we compared three versions of the face image varying in size and the
      amount of the face displayed. In experiment 2 we compared a fourth variant of the
      image with more prominent coloured eyes displayed closer to the focal chimpanzee.
      The chimpanzees did not look at the face images significantly more than at the
      control images in either experiment. Although there were trends for some
      individuals in each experiment to be slower to take high-value food items in the
      face conditions, these were not consistent or robust. We suggest that the extreme
      human sensitivity to cues of potential conspecific observation may not be shared
      with chimpanzees.

PMID- 24027344
TI  - Fossil evidence of the zygomycetous fungi.
AB  - Molecular clock data indicate that the first zygomycetous fungi occurred on Earth
      during the Precambrian, however, fossil evidence of these organisms has been slow
      to accumulate. In this paper, the fossil record of the zygomycetous fungi is
      compiled, with a focus on structurally preserved Carboniferous and Triassic
      fossils interpreted as zygosporangium-gametangia complexes and resembling those
      of modern Endogonales. Enigmatic microfossils from the Precambrian to Cenozoic
      that have variously been interpreted as, or compared to, zygomycetous fungi are
      also discussed. Among these, the spherical structures collectively termed
      'sporocarps' are especially interesting because of their complex investments and
      abundance in certain Carboniferous and Triassic rocks. Circumstantial evidence
      suggests that at least some 'sporocarp' types represent mantled zygosporangia.
      Zygomycetous fungi probably were an important element in terrestrial
      paleoecosystems at least by the Carboniferous. 

PMID- 24027345
TI  - DNA barcoding in Mucorales: an inventory of biodiversity.
AB  - The order Mucorales comprises predominantly fast-growing saprotrophic fungi, some
      of which are used for the fermentation of foodstuffs but it also includes species
      known to cause infections in patients with severe immune or metabolic
      impairments. To inventory biodiversity in Mucorales ITS barcodes of 668 strains
      in 203 taxa were generated covering more than two thirds of the recognised
      species. Using the ITS sequences, Molecular Operational Taxonomic Units were
      defined by a similarity threshold of 99 %. An LSU sequence was generated for each
      unit as well. Analysis of the LSU sequences revealed that conventional phenotypic
      classifications of the Mucoraceae are highly artificial. The LSU- and ITS-based
      trees suggest that characters, such as rhizoids and sporangiola, traditionally
      used in mucoralean taxonomy are plesiomorphic traits. The ITS region turned out
      to be an appropriate barcoding marker in Mucorales. It could be sequenced
      directly in 82 % of the strains and its variability was sufficient to resolve
      most of the morphospecies. Molecular identification turned out to be problematic
      only for the species complexes of Mucor circinelloides, M. flavus, M. piriformis
      and Zygorhynchus moelleri. As many as 12 possibly undescribed species were
      detected. Intraspecific variability differed widely among mucorealean species
      ranging from 0 % in Backusella circina to 13.3 % in Cunninghamella echinulata. A
      high proportion of clinical strains was included for molecular identification.
      Clinical isolates of Cunninghamella elegans were identified molecularly for the
      first time. As a result of the phylogenetic analyses several taxonomic and
      nomenclatural changes became necessary. The genus Backusella was emended to
      include all species with transitorily recurved sporangiophores. Since this
      matched molecular data all Mucor species possessing this character were
      transferred to Backusella. The genus Zygorhynchus was shown to be polyphyletic
      based on ITS and LSU data. Consequently, Zygorhynchus was abandoned and all
      species were reclassified in Mucor. Our phylogenetic analyses showed,
      furthermore, that all non-thermophilic Rhizomucor species belong to Mucor.
      Accordingly, Rhizomucor endophyticus was transferred to Mucor and Rhizomucor
      chlamydosporus was synonymised with Mucor indicus. Lecto-, epi- or neotypes were
      designated for several taxa. 

PMID- 24027346
TI  - Taxonomy and epidemiology of Mucor irregularis, agent of chronic cutaneous
      mucormycosis.
AB  - Mucormycosis usually presents as a progressive infection with significant angio
      invasion. Mucormycosis due to Mucor irregularis (formerly Rhizomucor variabilis
      var. variabilis), however, is exceptional in causing chronic cutaneous infection
      in immunocompetent humans, ultimately leading to severe morbidity if left
      untreated. More than 90 % of the cases known to date were reported from Asia,
      mainly from China. The nearest neighbour of M. irregularis is the saprobic
      species M. hiemalis. The aim of this study was to evaluate the taxonomic
      position, epidemiology, and intra- and inter-species diversity of M. irregularis
      based on 21 strains (clinical n = 17) by multilocus analysis using ITS, LSU, RPB1
      and RPB2 genes, compared to results of cluster analysis with amplified fragment
      length polymorphism (AFLP) data. By combining MLST and AFLP analyses, M.
      irregularis was found to be monophyletic with high bootstrap support, and
      consisted of five subgroups, which were not concordant in all partitions. It was
      thus confirmed that M. irregularis is a single species at 96.1-100 % ITS
      similarity and low recombination rates between populations. Some geographic
      structuring was noted with some localised populations, which may be explained by
      limited air-dispersal. The natural habitat of the species is likely to be in soil
      and decomposing plant material. 

PMID- 24027347
TI  - The family structure of the Mucorales: a synoptic revision based on comprehensive
      multigene-genealogies.
AB  - The Mucorales (Mucoromycotina) are one of the most ancient groups of fungi
      comprising ubiquitous, mostly saprotrophic organisms. The first comprehensive
      molecular studies 11 yr ago revealed the traditional classification scheme,
      mainly based on morphology, as highly artificial. Since then only single clades
      have been investigated in detail but a robust classification of the higher levels
      based on DNA data has not been published yet. Therefore we provide a
      classification based on a phylogenetic analysis of four molecular markers
      including the large and the small subunit of the ribosomal DNA, the partial actin
      gene and the partial gene for the translation elongation factor 1-alpha. The
      dataset comprises 201 isolates in 103 species and represents about one half of
      the currently accepted species in this order. Previous family concepts are
      reviewed and the family structure inferred from the multilocus phylogeny is
      introduced and discussed. Main differences between the current classification and
      preceding concepts affects the existing families Lichtheimiaceae and
      Cunninghamellaceae, as well as the genera Backusella and Lentamyces which
      recently obtained the status of families along with the Rhizopodaceae comprising
      Rhizopus, Sporodiniella and Syzygites. Compensatory base change analyses in the
      Lichtheimiaceae confirmed the lower level classification of Lichtheimia and
      Rhizomucor while genera such as Circinella or Syncephalastrum completely lacked
      compensatory base changes. 

PMID- 24027348
TI  - A comprehensive molecular phylogeny of the Mortierellales (Mortierellomycotina)
      based on nuclear ribosomal DNA.
AB  - The basal fungal order Mortierellales constitutes one of the largest orders in
      the basal lineages. This group consists of one family and six genera. Most
      species are saprobic soil inhabiting fungi with the ability of diverse
      biotransformations or the accumulation of unsaturated fatty acids, making them
      attractive for biotechnological applications. Only few studies exist aiming at
      the revelation of the evolutionary relationships of this interesting fungal
      group. This study includes the largest dataset of LSU and ITS sequences for more
      than 400 specimens containing 63 type or reference strains. Based on a LSU
      phylogram, fungal groups were defined and evaluated using ITS sequences and
      morphological features. Traditional morphology-based classification schemes were
      rejected, because the morphology of the Mortierellales seems to depend on culture
      conditions, a fact, which makes the identification of synapomorphic characters
      tedious. This study belongs to the most comprehensive molecular phylogenetic
      analyses for the Mortierellales up to date and reveals unresolved species and
      species complexes. 

PMID- 24027349
TI  - Phylogenetic lineages in Entomophthoromycota.
AB  - Entomophthoromycota is one of six major phylogenetic lineages among the former
      phylum Zygomycota. These early terrestrial fungi share evolutionarily ancestral
      characters such as coenocytic mycelium and gametangiogamy as a sexual process
      resulting in zygospore formation. Previous molecular studies have shown the
      monophyly of Entomophthoromycota, thus justifying raising the taxonomic status of
      these fungi to a phylum. Multi-gene phylogenies have identified five major
      lineages of Entomophthoromycota. In this review we provide a detailed discussion
      about the biology and taxonomy of these lineages: I) Basidiobolus
      (Basidiobolomycetes: Basidiobolaceae; primarily saprobic); II) Conidiobolus
      (Entomophthoromycetes, Ancylistaceae; several clades of saprobes and invertebrate
      pathogens), as well as three rapidly evolving entomopathogenic lineages in the
      family Entomophthoraceae centering around; III) Batkoa; IV) Entomophthora and
      allied genera; and V) the subfamily Erynioideae which includes Zoophthora and
      allied genera. Molecular phylogenic analysis has recently determined the
      relationships of several taxa that were previously unresolved based on morphology
      alone: Eryniopsis, Macrobiotophthora, Massospora, Strongwellsea and two as yet
      undescribed genera of Basidiobolaceae. 

PMID- 24027350
TI  - Examining new phylogenetic markers to uncover the evolutionary history of early
      diverging fungi: comparing MCM7, TSR1 and rRNA genes for single- and multi-gene
      analyses of the Kickxellomycotina.
AB  - The recently recognised protein-coding genes MCM7 and TSR1 have shown significant
      promise for phylogenetic resolution within the Ascomycota and Basidiomycota, but
      have remained unexamined within other fungal groups (except for Mucorales). We
      designed and tested primers to amplify these genes across early-diverging fungal
      clades, with emphasis on the Kickxellomycotina, zygomycetous fungi with
      characteristic flared septal walls forming pores with lenticular plugs.
      Phylogenetic tree resolution and congruence with MCM7 and TSR1 were compared
      against those inferred with nuclear small (SSU) and large subunit (LSU) rRNA
      genes. We also combined MCM7 and TSR1 data with the rDNA data to create 3- and 4
      gene trees of the Kickxellomycotina that help to resolve evolutionary
      relationships among and within the core clades of this subphylum. Phylogenetic
      inference suggests that Barbatospora, Orphella, Ramicandelaber and Spiromyces may
      represent unique lineages. It is suggested that these markers may be more broadly
      useful for phylogenetic studies among other groups of early-diverging fungi. 

PMID- 24027351
TI  - Age-dependent climate-growth relationships and regeneration of Picea abies in a
      drought-prone mixed coniferous forest in the Alps.
AB  - Within dry inner Alpine environments climate warming is expected to affect the
      development of forest ecosystems by changing species composition and inducing
      shifts in forest distribution. By applying dendroecological techniques we
      evaluated climate sensitivity of radial growth and establishment of Picea abies
      in a drought-prone mixed-coniferous forest in the Austrian Alps. Time series of
      annual increments were developed from > 220 trees and assigned to four age
      classes. While radial growth of old P. abies trees (mean age 121 and 174 yr)
      responded highly significant to May-June precipitation, young trees (mean age 28
      and 53 yr) were insensitive to precipitation in the current year. Because tree
      age was closely correlated to height and diameter (r2 = 0.709 and 0.784,
      respectively), we relate our findings to the increase in tree size rather than
      age per se. Synchronicity found among trend in basal area increment and tree
      establishment suggests that canopy openings increased light and water
      availability, which favoured growth and establishment of moderately shade
      tolerant P. abies. We conclude that although P. abies is able to regenerate at
      this drought prone site, increasing inter-tree competition for water in dense
      stands gradually lowers competitive strength and restricts scattered occurrence
      to dry-mesic sites.

PMID- 24027352
TI  - Parenting and Early Adolescent Internalizing: The Importance of Teasing Apart
      Anxiety and Depressive Symptoms.
AB  - This community-based study examined differences in parenting quality and parent
      symptoms for youth in four categories: anxious (elevated anxiety symptoms),
      depressed (elevated depressive symptoms), comorbid (elevated anxiety and
      depressive symptoms), and nonelevated (elevations of neither type). Respondents
      were 976 young adolescents (mean age = 11.3) and their parents (912 mothers, 647
      fathers) randomly selected from 28 rural/small town communities. Results
      indicated that depressed and comorbid groups were associated with significantly
      lower parenting quality and higher parent psychopathology compared to the
      nonelevated and anxious groups. This pattern was generally consistent across
      reporters (youth, mother, and father) and four domains of or related to parenting
      (support/warmth, conflict/anger, general child management (GCM), and parent
      psychopathology). Results highlight the importance of accounting for comorbidity
      when examining relationships between psychopathology symptoms and related
      variables such as parenting. Implications include the need to address
      relationships with parents when intervening with youth at risk for or
      experiencing elevated depressive symptoms.

PMID- 24027353
TI  - Developmental changes in effects of risk and valence on adolescent decision
      making.
AB  - Recent research on risky decision-making in adults has shown that both the risk
      in potential outcomes and their valence (i.e., whether those outcomes involve
      gains or losses) exert dissociable influences on decisions. We hypothesised that
      the influences of these two crucial decision variables (risk and valence) on
      decision-making would vary developmentally during adolescence. We adapted a risk
      taking paradigm that provides precise metrics for the impacts of risk and
      valence. Decision-making in 11-16 year old female adolescents was influenced by
      both risk and valence. However, their influences assumed different developmental
      patterns: the impact of valence diminished with age, while there was no
      developmental change in the impact of risk. These different developmental
      patterns provide further evidence that risk and valence are fundamentally
      dissociable constructs and have different influences on decisions across
      adolescence.

PMID- 24027354
TI  - Influence of hydrogen cations on kinetics and equilibria of heavy-metal sorption
      by algae-sorption of copper cations by the alga Palmaria palmata (Linnaeus) Weber
      & Mohr (Rhodophyta).
AB  - The influence of hydrogen cations on kinetics and equilibria of sorption of
      copper cations by the marine alga Palmaria palmata (Linnaeus) Weber & Mohr was
      studied under static conditions. The competitive effect of the H+ cations is
      described, which influenced the uncertainty of evaluation of the alga sorption
      capacity. Under static conditions, the variation of the Cu2+/H+ concentration
      ratio during sorption was found nonmonotonic. The Langmuir isotherm model was
      used to determine the sorption capacity of the alga, namely 12.4 mg g-1 of dry
      algae mass. A similar value was determined from the kinetic parameters of the
      ionic exchange which is considered a pseudo-second-order chemical reaction. The
      consistent results indicated that the mathematical models used correctly
      described the equilibria and kinetics of the ionic exchange between algae and
      solutions.

PMID- 24027355
TI  - Effect on supplementation of Spirulina maxima enriched with Cu on production
      performance, metabolical and physiological parameters in fattening pigs.
AB  - In this paper, the effect of addition of the biomass of Spirulina maxima enriched
      with copper (Sm-Cu) to the animal feed is discussed. The biomass was cultivated
      in the photobioreactor with the capacity of 10 m3. After the biosorption process,
      the enriched biomass was investigated as the source of valuable nutrients. The
      feeding experiment was conducted for 87 days. The study was performed in
      individual rearing pens, with controlled microclimate, feed and water were
      available semi-ad libitum. Piglets (24) were divided into two groups (control and
      experimental). The experimental group was fed with addition of the biomass of Sm
      Cu instead of inorganic salts. There were no statistically significant
      differences between the average daily and periodic weight gain, daily and
      periodic feed collection, as well as feed conversion ratio. There were no
      statistically significant differences between the amount of N excreted in faeces
      and urine, when considering the retention of N, both in relation to the consumed
      N, and relative N digested which was at a similar level. In the experimental
      group in comparison to the control group, the lower low-density lipoprotein
      cholesterol by 17.05 % (P < 0.05) and total cholesterol by 9.43 % (P < 0.05) were
      observed. Additionally, the increase of parameter a* of 13 % (P < 0.05) and the
      reduction of the natural leakage by 34 % (P < 0.05) were found.

PMID- 24027356
TI  - Effects of a diet enriched with polyunsaturated, saturated, or trans fatty acids
      on cytokine content in the liver, white adipose tissue, and skeletal muscle of
      adult mice.
AB  - This study analyzed the effect of diet enriched with 30% lipids on cytokines
      content in different tissues. Swiss male mice were distributed into four groups
      treated for 8 weeks with control (C, normolipidic diet); soybean oil (S); lard
      (L); and hydrogenated vegetable fat (H). We observed an increase in carcass fat
      in groups S and L, and the total amount of fatty deposits was only higher in
      group L compared with C group. The serum levels of free fatty acids were lower in
      the L group, and insulin, adiponectin, lipid profile, and glucose levels were
      similar among the groups. IL-10 was lower in group L in mesenteric and
      retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose
      tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group,
      and a positive correlation between TNF-alpha and IL-10 was observed in the livers
      of groups C, L, and H and in the muscles of all groups studied. The results
      suggested relationships between the quantity and quality of lipids ingested with
      adiposity, the concentration of free fatty acids, and cytokine production in
      white adipose tissue, gastrocnemius muscle, and liver. 

PMID- 24027358
TI  - The management of family conflict in palliative care.
AB  - We review the literature on family conflict in palliative care. The prevalence
      and common sources of conflict are discussed, including historical issues of
      tension, differing coping styles, the division of labour, and the presence of
      acute or chronic mental illness within the family. Assessment and intervention
      strategies used in Family Focused Grief Therapy (FFGT), a family-centred
      preventive intervention that begins during palliative care and continues during
      bereavement, are presented, with special consideration given to research on
      treatment decision-making, cultural issues, special-needs populations, and the
      management of crises within the family. We conclude with a discussion of
      challenges that frequently impede conflict resolution and with suggestions for
      addressing these difficulties in the palliative care setting.

PMID- 24027357
TI  - Downregulation of NOX4 expression by roflumilast N-oxide reduces markers of
      fibrosis in lung fibroblasts.
AB  - The phosphodiesterase 4 inhibitor roflumilast prevents bleomycin- (BLM-) induced
      lung fibrosis in animal models. However, its mechanism of action remains unknown.
      We investigated whether roflumilast N-oxide (RNO), the active metabolite of
      roflumilast, can modulate in vitro the oxidative effects of BLM on human lung
      fibroblasts (HLF). In addition, since BLM increases the production of F2
      isoprostanes that have per se fibrogenic activity, the effect of RNO on oxidative
      stress and fibrogenesis induced by the F2-isoprostane 8-epi-PGF2alpha was
      investigated. HLF were preincubated either with the vehicle or with RNO and
      exposed to either BLM or 8-epi-PGF2alpha. Proliferation and collagen synthesis
      were assessed as [(3)H]-thymidine and [(3)H]-proline incorporation. Reactive
      oxygen species (ROS) and F2-isoprostanes were measured. NADPH oxidase 4 (NOX4)
      protein and mRNA were also evaluated. BLM increased both cell proliferation and
      collagen synthesis and enhanced ROS and F2-isoprostane production. These effects
      were significantly prevented by RNO. Also, RNO significantly reduced the increase
      in both NOX4 mRNA and protein, induced by BLM. Finally, 8-epi-PGF2alpha   per se
      stimulated HLF proliferation, collagen synthesis, and NOX4 expression and ROS
      generation, and RNO prevented these effects. Thus, the antifibrotic effect of RNO
      observed in vivo may be related to its ability to mitigate ROS generation via
      downregulation of NOX4.

PMID- 24027359
TI  - Preface JCDR 2013 issue 2.

PMID- 24027360
TI  - Surgical revascularization techniques for diabetic foot.
AB  - Diabetes is an important risk factor for atherosclerosis. The diabetic foot is
      characterized by the presence of arteriopathy and neuropathy. The vascular damage
      includes non-occlusive microangiopathy and macroangiopathy. Diabetic foot wounds
      are responsible for 5-10% of the cases of major or minor amputations. In fact,
      the risk of amputation of the lower limbs is 15-20% higher in diabetic
      populations than in the general population. The University of Texas
      classification is the reference classification for diabetic wounds. It
      distinguishes non-ischemic wounds from ischemic wounds which are associated with
      a higher rate of amputation. The first principles of treatment are the control of
      pain of an eventual infection. When ischemia is diagnosed, restoration of
      pulsatile blood flow by revascularization may be considered for salvaging the
      limb. The treatment options are angioplasty with or without stenting and surgical
      bypass or hybrid procedures combining the two. Distal reconstructions with
      anastomosis to the leg or pedal arteries have satisfactory limb-salvage rates.
      Subintimal angioplasty is a more recent endovascular technique. It could be
      suggested for elderly patients who are believed to be unsuitable candidates for a
      conventional bypass or angioplasty. The current article would focus on the
      various revascularization procedures. 

PMID- 24027361
TI  - Inadvertent left aorto-coronary dissection following percutaneous coronary
      intervention treated successfully by bail-out left main coronary artery stenting.
AB  - Left main coronary artery (LMCA) dissection occurs very rarely following
      percutaneous coronary intervention (PCI). It caused major consequences with no
      flow in coronary artery and requires immediate surgical or percutaneous
      intervention. We are reporting a case of 42-year-male patient who presented with
      effort angina. Coronary angiogram revealed significant stenosis in left anterior
      descending (LAD) and left circumflex (LCX) coronary artery. During removal of
      angioplasty balloon and guide wire after successfully stenting in LAD and balloon
      angioplasty in LCX, guiding catheter induced dissection of LMCA was happened.
      Subsequently, LMCA was stented; kissing balloon dilatation was done at carina &
      TIMI III flow re-established. 

PMID- 24027362
TI  - Endothelial dysfunction and hypertension in obstructive sleep apnea - Is it due
      to intermittent hypoxia?
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is a prevalent disorder causing
      hypertension. Endothelial dysfunction appears to underlie development of
      hypertension. It is not known whether hypoxia during sleep is necessarily the
      prerequisite process for endothelial dysfunction and hypertension in OSA. We
      therefore examined the relationship between endothelial-dependent vasodilatory
      capacity, hypoxia and circulating angiogenesis inhibitors in OSA. METHODS AND
      RESULTS: We studies 95 subjects with and without OSA and hypertension.
      Endothelial-dependent vasodilation was assessed using brachial artery flow
      mediated vasodilation method (FMD). Plasma angiogenesis inhibitors, endoglin
      (sEng) and fms-like tyrosine kinase-1 (sFlt-1), were measured using ELISA. The
      apnea-hypopnea indexes were 41 +/- 5 and 48 +/- 4 events/hr in normotensive OSA
      (N-OSA) and hypertensive OSA (H-OSA), respectively, indicating severe OSA. The
      sleep time spent with SaO2 < 90% (T < 90%) were 34 +/- 8 and 40 +/- 9 min,
      respectively. FMD was markedly impaired in H-OSA (8.0% +/- 0.5) compared to N-OSA
      (13.5% +/- 0.5, P < 0.0001), H-non-OSA (10.5% +/- 0.8, P < 0.01), and N-non-OSA
      (16.1% +/- 1.0, P < 0.0001). There was no correlation between T < 90% and FMD.
      Both OSA groups had elevated levels of sFlt-1 (62.4 +/- 5.9 and 63.9 +/- 4.7
      pg/ml) compared to N-non-OSA (32.1 +/- 6.5, P = 0.0008 and P = 0.0004,
      respectively) and H-non-OSA (41.2 +/- 7.0, P < 0.05 and P = 0.03, respectively).
      In contrast, sEng was only elevated in H-OSA (4.20 +/- 0.17 ng/ml) compared with
      N-OSA (3.64 +/- 0.14, P = 0.01) and N-non-OSA (3.48 +/- 0.20, P = 0.01). There
      was a modest but statistically significant inverse correlation between sEng and
      FMD in only H-OSA group (r = -0.38, P < 0.05). CONCLUSION: These data show that
      patients with OSA and hypertension have marked impairment of FMD, independent of
      hypoxia exposure, which is associated with increased sEng.

PMID- 24027363
TI  - Effect of Pollypill on cardiovascular parameters: Systematic review and meta
      analysis.
AB  - BACKGROUND: Wald and law in their landmark paper published in BMJ in 2003
      hypothesized that the use of fixed dose combination of statins, beta blockers,
      angiotensin-converting-enzyme inhibitor (ACE) inhibitor, and aspirin (Pollypill)
      may decrease cardiovascular disease by >80% if Pollypills are used as primary
      prevention. Many clinical trials were started to test this hypothesis. The
      present systematic review and meta-analysis aims to assess the available clinical
      trials to see the effect of Pollypill on cardiovascular mortality and on other
      risk factors that linked with increase in cardiovascular events. MATERIALS AND
      METHODS: Available databases were searched with different specific terms and
      combination of key words. All randomized clinical trials exploring the effect of
      Pollypill on various cardiovascular parameters were included in the analysis.
      Primary endpoints as decided were cardiovascular mortality, systolic blood
      pressure, diastolic blood pressure, and low-density lipoprotein (LDL)
      cholesterol. Effect of Pollypill on high-density lipoprotein (HDL) cholesterol,
      total cholesterol, triglycerides, the number of participants who discontinued
      treatment, and the number of participants who experienced side effects were
      measured and analyzed as secondary outcomes. Both fixed and random models were
      used for analysis. Analysis was performed by comprehensive meta-analysis
      software. RESULTS: Six trials were included in systematic review. It was observed
      that Pollypill decreases systolic and diastolic blood pressure (P = 0.000).
      Pollypill was also found to decrease LDL cholesterol, total cholesterol, and
      triglyceride as compared to the control (all P = 0.000); however, there was no
      significant improvement in HDL (P = 0.39). The number of participants in whom
      side effects were observed were found to be more in the Pollypill group (odds
      ratio = 1.73, P = 0.000). It was also observed that dropouts were more in the
      Pollypill group than in the control group (odds ratio = 1.48, P = 0.02). Due to
      the lack of sufficient data effect of Pollypill, cardiovascular mortality could
      not be assessed. CONCLUSION: Pollypill decreases various surrogate endpoints
      related to cardiovascular outcome, but with the increased chance of side effects
      as compared to control.

PMID- 24027364
TI  - A clinical scoring system in undifferentiated chest pain predicting undetectable
      troponin concentration.
AB  - BACKGROUND: Chest pain is the most common reason for emergency admission to
      hospital, but the majority of these are due to non-cardiac pain. We sought to
      determine which combination of clinical features is more likely to predict an
      undetectable troponin level in patients presenting with chest pain. METHODS: We
      collected data over a two-month period on consecutive patients presenting acutely
      to hospital with chest pain and who had a troponin I measured. We recorded basic
      demographics, risk factors, pain distribution, associated symptoms, physical
      findings and ECG changes. The parameters significantly associated with troponin
      positivity were entered into a stepwise logistic regression analysis and the
      resulting model's coefficients were used to construct a simple clinical score to
      categorise patients into low, medium or high probability of having a positive
      troponin. RESULTS: 26 of 157 (16.6%) patients had a positive troponin. The
      variables retained in the regression model were: age >65, heart rate >80,
      previous myocardial infarction, diabetes and pain radiating to either arm. The
      model showed good discrimination (area under ROC curve 0.869, 95% CI 0.806 -
      0.917). Using the regression model's coefficients, patients were grouped into
      low, intermediate or high probability groups. Being in the low probability group
      had a negative predictive value of 97.8% and being in the high probability group
      had a positive predictive value of 65.2%. The majority (73.9%) of patients could
      be categorised as either low or high probability. DISCUSSION: This simple scoring
      system, if prospectively validated, may be useful in identifying low risk
      patients with chest pain who are unlikely to have elevation of serum troponin
      concentration.

PMID- 24027365
TI  - Anti-CCP antibody in patients with established rheumatoid arthritis: Does it
      predict adverse cardiovascular profile?
AB  - BACKGROUND: Rheumatoid arthritis (RA) is an independent risk factor for adverse
      cardiovascular (CV) events that accounts for a significant proportion of
      mortality among these patients. Anti-CCP antibodies are associated with higher
      frequency of extra-articular manifestations and poorer outcomes in RA. AIMS: To
      determine the role of anti-cyclic citrullinated peptide (CCP) antibody as an
      independent risk factor for developing CV complications as documented by carotid
      intima medial thickness and abnormal echocardiography in established RA patients.
      MATERIALS AND METHODS: Eighty patients of RA having disease duration of at least
      3 years participated in this hospital-based, cross-sectional, and observational
      study. Forty patients were anti-CCP antibody positive. Patients of established RA
      having known CV risk factors, known heart disease, or family history of premature
      ischemic heart disease were excluded. RESULTS: Anti-CCP positive group had early
      morning stiffness, tender and swollen joint count, and c-reactive protein (CRP)
      level significantly higher than those in anti-CCP negative group. Average intima
      medial thicknesses of common carotid arteries were also significantly higher
      among anti-CCP positive group (P = 0.029) and were positively correlated with
      patients' age and disease duration. Lower left ventricular ejection fraction and
      left ventricular diastolic dysfunction were more commonly dispersed among the
      anti-CCP positive patients with P values of 0.01 and 0.034, respectively. Mild
      pericardial thickening was documented among 12.5% patients of anti-CCP positive
      group, while none of the anti-CCP negative patients had similar findings in
      echocardiography. CONCLUSION: This study stressed on the important role of anti
      CCP antibody in myocardial dysfunction due to inflammation in RA patients. Both
      atherosclerotic vascular involvement and cardiac abnormalities including
      pericardial, myocardial, and endocardial involvements were higher among anti-CCP
      positive RA patients. Hence, patients with high titer of anti-CCP antibody
      associated with prolonged disease duration and increased disease activity should
      be evaluated for CV morbidity more meticulously.

PMID- 24027366
TI  - Clinical profile of acute myocardial infarction in elderly patients.
AB  - CONTEXT: The aim of study was to determine the difference in presentation, risk
      factors, complications, management and outcome of elderly and young patients with
      acute myocardial infarction (AMI). SETTINGS AND DESIGN: Tertiary care center;
      prospective observational study. MATERIALS AND METHOD: The study included 200
      consecutive patients with AMI admitted in the ICCU, in a tertiary care center in
      West India. The group I consisted of 107 patients aged equal to or above 65 years
      and the group II consisted of 93 patients aged below 65 years. STATISTICAL
      ANALYSIS: Two tailed student's t test and Chi-square statistics (Fisher's test)
      for P value. RESULTS: The male female ratio was 1.27:1 and 3.43:1 in group I and
      group II respectively. Atypical presentations were more likely in the elderly,
      with shortness of breath as the most common presentation (40.18% versus 15.05%; P
      < 0.05. Risk factors like hypertension, dyslipidemia and diabetes were equally
      present in both groups but obesity, smoking and family history of coronary artery
      disease was more prevalent in younger age group (P < 0.05). The elderly were
      significantly less frequently revascularized (P < 0.05). Time from symptom onset
      to hospital admission was significantly longer in the case of elderly patients (P
      < 0.05). The elderly were more likely to have complications of cardiac failure (P
      < 0.05) and arrhythmias especially atrio-ventricular (AV) blocks. The elderly
      were also less likely to receive beta-blockers (P < 0.05). In-hospital mortality
      was higher in the elderly (P < 0.001). CONCLUSION: We conclude that the
      manifestations of AMI are more subtle in the elderly, with different risk
      factors.

PMID- 24027367
TI  - High prevalence of cardiovascular risk factors among policemen in Puducherry,
      South India.
AB  - BACKGROUND: Diabetes mellitus and hypertension (HT) are common diseases in
      adulthood, pre-disposing to many cardiovascular complications, posing a major
      public health challenge. Few studies have reported increased prevalence of
      cardiovascular disease risk factors and type 2 diabetes in policemen. Hence, this
      study aims to assess the prevalence of cardiovascular risk factors such as
      diabetes, HT, smoking, alcohol intake, and obesity among policemen. MATERIALS AND
      METHODS: A cross-sectional study was carried out in 2008-2009 among 256 policemen
      in Puducherry, South India. Policemen were selected by simple random sampling.
      Socio-demographic details and some of the risk factors such as alcohol intake and
      smoking history were obtained using a pre-tested, structured questionnaire.
      Presence of stress was measured using the professional life stress score
      questionnaire. Blood pressure, waist circumference, and hip circumference were
      measured by standard methods. Fasting blood sugar was estimated using a
      glucometer. Serum cholesterol was also measured. Lipid profile was measured for a
      randomly chosen subgroup of 50 participants. RESULTS: Mean age of study
      participants was 40.9 years (SD +/- 10.9). Out of the study subjects, 23% (n =
      60) were known diabetic and 16.8% (n = 43) were known hypertensive. Prevalence of
      diabetes among study participants was 33.6% (CI: 27.8%-39.6%). Prevalence of HT
      among study participants was 30.5% (CI: 24.9%-36.5%). Seventy percent (n = 178)
      had at least moderate range of stress in their life related to their profession
      and 4% (n = 11) had stress as a "problem" in their life. CONCLUSIONS: Burden of
      cardiovascular risk factors such as diabetes and HT was high among police
      personnel of Puducherry.

PMID- 24027368
TI  - Effect of obesity on cardiometabolic risk factors in Asian Indians.
AB  - OBJECTIVES: To determine the prevalence of overweight and obesity and their
      effects on cardiometabolic risk factors in a representative sample of urban
      population in Eastern India. MATERIALS AND METHODS: A population-based survey was
      conducted among a randomly selected study population aged 20-80 years in an urban
      population of Berhampur city of Eastern India. Both anthropometric and
      biochemical information were collected, in addition to detailed information on
      classical cardiometabolic risk factors. Both descriptive and inferential
      statistical analyses were performed. Obesity and overweight were defined based on
      the revised Asian-Pacific population criteria (Body mass index [BMI] >=25 kg/m(2)
      and >=23 kg/m(2), respectively). RESULTS: The age-standardized rates of obesity
      and overweight are 36.8% (Males: 33.2%; Females: 40.8%) and 17.6%, (Males: 20.4%;
      Females: 15.1%) respectively, i.e., over half are either obese or overweight in
      this study population. Compared to the World Health Organization (WHO) standard
      cutoff criteria of overweight [BMI >=25 kg/m(2)] and obesity [BMI >30 kg/m(2)],
      the cardiometabolic risk factors studied showed a significant incremental rise
      even with the lower cutoffs of the revised Asia-Pacific criteria. Older age,
      female gender, family history of diabetes, being hypertensive,
      hypertriglyceridemia, hypercholesterolemia, physical inactivity and middle to
      higher socioeconomic status significantly contributed to increased obesity risk
      among this urban population. CONCLUSION: One-third of the urban populations are
      obese in Eastern India - an underestimate compared to the standard BMI cutoff
      criteria. Nevertheless, significant associations of the classical cardiometabolic
      risk factors with obesity were observed using the revised Asia-Pacific criteria
      clearly indicating a more aggressive cardiovascular prevention strategy for Asian
      Indians.

PMID- 24027369
TI  - Initial misdiagnosis of acute flail mitral valve is not infrequent: The role of
      echocardiography.
AB  - BACKGROUND: Acute flail mitral valve frequently results in severe mitral
      regurgitation. However, its clinical presentation can be similar to other disease
      processes, potentially leading to initial misdiagnosis and a morbid outcome. We
      sought to analyze baseline characteristics, clinical presentations, time to
      diagnosis, and in-hospital mortalities of patients with the acute flail mitral
      valve. METHODS: Two hundred and sixty two consecutive echocardiograms with severe
      mitral regurgitation performed between February 2005 and October 2010 at the Jack
      D. Weiler Hospital (Bronx, New York, USA) were reviewed. Adult patients who had
      presented with new onset flail mitral valves were selected for this retrospective
      study. RESULTS: Fifteen patients were found to have acute flail mitral valve. The
      majority was elderly male. Over half presented to the emergency room with a
      sudden onset of dyspnea. A mitral regurgitant murmur was appreciated in only a
      third of the patients. The chest X-ray of five patients had no acute pulmonary
      findings, whereas, two were found to have gross unilateral pulmonary edema.
      Clinically, 60% were misdiagnosed on admission. Using echocardiogram, the correct
      diagnosis of flail mitral valve was made in all cases, however, only 40% on the
      day of presentation. The maximum time to echocardiographic diagnosis was 4 days.
      The main cause of acute flail mitral valve was degenerative disease. Seven
      patients were managed surgically. Overall, there was only one mortality (7%)
      during incident hospitalization. CONCLUSIONS: Initial misdiagnosis of acute flail
      mitral valve happens frequently. Early echocardiographic exam is essential in the
      timely diagnosis and management of acute flail mitral valve.

PMID- 24027370
TI  - Pulsatile versus non-pulsatile flow to reduce cognitive decline after coronary
      artery bypass surgery: A randomized prospective clinical trial.
AB  - BACKGROUND: In this prospective study, we aimed to compare the effect of
      pulsatile and non-pulsatile flow on the cognitive functions in patients
      undergoing coronary artery bypass surgery. METHODS: Patients scheduled for their
      first coronary artery bypass surgery (n = 148) were randomly assigned to the
      pulsatile flow group (Group A, n = 75) or non-pulsatil group (Group B, n = 73).
      Cognitive performance was assessed with (MoCA) montreal cognitive assessment test
      performed by psychologists before coronary artery bypass surgery and 1 month
      after the operation. RESULTS: Mild cognitive impairment was seen in 12 (16%)
      patients and serious cognitive impairment was seen in 1 (1.33%) patient in the
      pulsatile flow group. In the other group, mild cognitive impairment was detected
      in 23 (31.50%) patients and serious cognitive decline was found in 3 (4.10%)
      patients. Mean MoCA scores were 25.86 +/- 2.62 in group A and 22.12 +/- 2.20 in
      group B. The difference between two groups was statistically significant (P =
      0.041). CONCLUSIONS: We suggest that pulsatile flow has beneficial effects to
      decrease cognitive dysfunction in patients undergoing on-pump coronary artery
      bypass surgery.

PMID- 24027371
TI  - Study the mechanical pulmonary changes in patients with congestive heart failure
      (CHF) by impulse oscillometry.
AB  - BACKGROUND: Heart failure is one of the most leading cause of death worldwide,
      but the mechanical characteristics of the pulmonary system in these patients have
      not been studied enough. The aim of this study was to measure mechanical
      pulmonary changes in patients with congestive heart failure (CHF) by using
      impulse oscillometry (IOS), which can obtain data by simpler means and
      independently from respiratory muscle strength. MATERIALS AND METHODS: We
      assessed 24 CHF patients and 24 controls by spirometry and IOS using the Jaeger
      IOS system. IOS measures central and peripheral airway resistances (R20, R5) and
      central and peripheral reactances (X20, X5) using sound waves with different
      frequencies, which superimposed on the patients respiratory tidal volume and then
      records reflects. P value < 0.05 was taken to be significant. RESULTS: The mean
      age of patients and controls was 61 +/- 10 and 57 +/- 7 years, respectively. The
      mean ejection fraction (EF) was 37 +/- 17% for patients and 55 +/- 7% for
      controls. Patients had a lower X5 (-0.20 +/- 0.13 vs -0.13 +/- 0.07; P < 0.05),
      forced expiratory volume in 1 second (FEV1; 2.26 +/- 0.68 vs 3.09 +/- 0.82: P <
      0.01 L/min), and forced vital capacity (FVC; 2.55 +/- 0.86 vs 3.32 +/- 0.87; P <
      0.05) compared to the controls. They also had elevated R5: 0.37 +/- 0.21 vs 0.27
      +/- 0.09; P < 0.06). X5 was correlated with spirometric abnormalities (P < 0.05)
      and was lower in patients than in controls. CONCLUSION: X5 was lower and R5 was
      higher in patients than in controls. CHF patients can be assessed by IOS more
      comfortable than by spirometry. IOS can reliably measure peripheral airway
      resistance in this group of patients.

PMID- 24027372
TI  - Age and clinical outcomes in patients presenting with acute coronary syndromes.
AB  - CONTEXT: Elderly patients have more cardiovascular risk factors and a greater
      burden of ischemic disease than younger patients. AIMS: To examine the impact of
      age on clinical presentation and outcomes in patients presenting with acute
      coronary syndrome (ACS). METHODS AND MATERIAL: Collected data from the 2nd Gulf
      Registry of Acute Coronary Events (Gulf RACE-2), which is a prospective
      multicenter study from six adjacent Arab Middle Eastern Gulf countries. Patients
      were divided into 3 groups according to their age: <=50 years, 51-70 years and
      >70 years and their clinical characteristics and outcomes were analyzed.
      Mortality was assessed at one and 12 months. STATISTICAL ANALYSIS USED: One-way
      ANOVA test for continuous variables, Pearson chi-square (X (2)) test for
      categorical variables and multivariate logistic regression analysis for
      predictors were performed. RESULTS: Among 7930 consecutive ACS patients; 2755
      (35%) were <=50 years, 4110 (52%) were 51-70 years and 1065 (13%) >70 years old.
      The proportion of women increased with increasing age (13% among patients <=50
      years to 31% among patients > 70 years). The risk factor pattern varied with age;
      younger patients were more often obese, smokers and had a positive family history
      of CAD, whereas older patients more likely to have diabetes mellitus,
      hypertension, and dyslipidemia. Advancing age was associated with under-treatment
      evidence-based therapies. Multivariate logistic regression analysis after
      adjusting for relevant covariates showed that old age was independent predictors
      for re-ischemia (OR 1.29; 95% CI 1.03-1.60), heart failure (OR 2.8; 95% CI 2.17
      3.52) and major bleeding (OR 4.02; 95% CI 1.37-11.77) and in-hospital mortality
      (age 51-70: OR 2.67; 95% CI 1.86-3.85, and age >70: OR 4.71; 95% CI 3.11-7.14).
      CONCLUSION: Despite being higher risk group, elderly are less likely to receive
      evidence-based therapies and had worse outcomes. Guidelines adherence is highly
      recommended in elderly.

PMID- 24027373
TI  - Prevalence of cardiovascular risk factors among rural population of elderly in
      Wardha district.
AB  - BACKGROUND: Cardiovascular diseases (CVD) are a leading cause of mortality among
      adults in India, and their risk factors (tobacco, hypertension, diabetes,
      overweight, and obesity) are common. Most risk-factor surveys have focused on
      young and middle aged adults. We measured the prevalence of risk factors for CVD
      among elderly (age 60 years or more) in rural India. METHODS AND RESULTS: In a
      door-to-door cross-sectional survey we did a non-laboratory based assessment of
      risk factors (smoking or tobacco use in any form, diabetes mellitus, either known
      or newly detected hypertension, abnormal waist-hip-ratio, or a high body mass
      index) among elderly living in 23 villages in rural central India. Laboratory
      based assessment of risk factors was done in those who had two or more of the
      five measured conventional risk factors. We compared the distribution of risk
      factors between men and women. Among 2424 elderly included in the study (51%
      women, mean age 67), the prevalence of smokeless tobacco use was 50.8% (95% CI
      48.1-52.8; smoking 10.5% (95% CI 9.3-11.8); and hypertension46.3% (95% CI 44.3
      48.4). Only 10.2% participants were previously known to have had hypertension,
      and remaining 36.1% were detected to be hypertensive during the survey. A total
      of 8.2%(95% CI 7.0-9.5) participants were overweight and 4.1% (95% CI 3.3-4.9)
      had central obesity. The prevalence of dyslipidemia in those who underwent blood
      based tests was 40.6% (95% CI 36.5-44.9); and hyperglycemia 4.9% (95% CI 3.2
      7.1). CONCLUSIONS: Strategies to reduce the risk of cardiovascular disorders
      among elderly should be focused on reducing tobacco use and early detection and
      optimal control of hypertension.

PMID- 24027374
TI  - A patient with rheumatic heart disease presented with central cyanosis due to
      acquired methemoglobinemia during late pregnancy - A rare association.
AB  - A 21-year-old pregnant female of known rheumatic heart disease presented to us
      for evaluation of central cyanosis during her late pregnancy. Though she was
      investigated for any associated congenital heart disease or pulmonary
      arteriovenous fistula, but incidentally she was diagnosed of having acquired
      methemoglobinemia. Her serum methemoglobin level was 33% which was far above the
      normal range. Ultimately, she was managed conservatively and delivered through
      elective caesarean section. Though the delivered baby was lethargic after birth,
      but later he was improved and discharged. This was the first case reported so far
      that a pregnant patient of rheumatic heart disease developed cyanosis due to
      methemoglobinemia. 

PMID- 24027375
TI  - Isolated pericardial echinococcosis: Perioperative transesophageal
      echocardiographic evaluation.
AB  - Hydatid cyst (HC) is a human parasitic disease caused by the larval stage of
      Echinococcus granulosus. Cardiac involvement is rare and occurs in 0.5%-2% of
      patients with hydatid cyst, but isolated pericardial hydatid cyst is rarer still.
      We present two cases of isolated pericardial hydatid cyst who presented with
      precordial chest pain and dyspnea. In both the cases, HC were diagnosed by
      transthoracic echo (TTE), Computed Tomography/Magnetic Resonance and positive
      hydatid serology. Intraoperatively transesophageal echo (TEE) revealed unilocular
      transitional cystic lesion the transverse pericardial sinus in one case and
      multilobulated active cystic lesion in another. The report highlights the role of
      TEE in diagnosis and evaluation of cardiac HC. Both the cases underwent surgical
      resection followed by albendazole therapy to prevent recurrence. 

PMID- 24027376
TI  - Biventricular noncompaction presented with symptomatic complete heart block -
      Report of a case and review of literature.
AB  - Ventricular noncompaction has been recognized as a distinct form of rare
      cardiomyopathy characterized by numerous, prominent ventricular trabeculations
      and deep intertrabecular recesses and is caused by a disorder of endomyocardial
      morphogenesis. Concomitance of either valvular pathologies or complete
      atrioventricular block with biventricular noncompaction has rarely been reported.
      Herein, we present a case of 67 years old male presented with syncopal attack and
      congestive heart failure due to biventricular noncompaction with significant left
      ventricular dysfunction associated with complete atrioventricular block. He was
      formerly diagnosed as dilated cardiomyopathy for last 2 years. Review of
      literatures of all reported cases has been discussed. 

PMID- 24027377
TI  - Simple nonsurgical method of reduction of coronary catheter knot.
AB  - Knotting and kinking of the coronary catheter is one of the complications during
      diagnostic or interventional procedures. These complications can be tackled
      percutaneously without subjecting the patient to surgery. We are reporting one
      such case of catheter knotting and how it was reduced percutaneously. 

PMID- 24027378
TI  - Acute myocardial infarction being the presentation of dengue myocarditis.
AB  - Dengue fever is one of the most common vector-borne viral infections in tropical
      countries. Myocarditis is an uncommon complication of severe dengue fever.
      Sometimes, dengue myocarditis masquerades as acute myocardial infarction. We
      report here a case of a 22-year-old female, who presented with acute chest pain
      five days after the onset of a febrile episode. Initially she was diagnosed as
      acute myocardial infarction depending on the biochemical and echocardiography
      evidence. However, later investigation confirmed she was suffering from
      myocarditis due to dengue fever, which mimicked acute myocardial infarction. A
      Medline search revealed only few other reported cases of dengue myocarditis that
      mimicked of acute myocardial infarction. 

PMID- 24027379
TI  - Interpolation Error Estimates for Mean Value Coordinates over Convex Polygons.
AB  - In a similar fashion to estimates shown for Harmonic, Wachspress, and Sibson
      coordinates in [Gillette et al., AiCM, to appear], we prove interpolation error
      estimates for the mean value coordinates on convex polygons suitable for standard
      finite element analysis. Our analysis is based on providing a uniform bound on
      the gradient of the mean value functions for all convex polygons of diameter one
      satisfying certain simple geometric restrictions. This work makes rigorous an
      observed practical advantage of the mean value coordinates: unlike Wachspress
      coordinates, the gradient of the mean value coordinates does not become large as
      interior angles of the polygon approach pi.

PMID- 24027380
TI  - Optimal Perturbation Control of General Topology Molecular Networks.
AB  - In this paper, we develop a comprehensive framework for optimal perturbation
      control of dynamic networks. The aim of the perturbation is to drive the network
      away from an undesirable steady-state distribution and to force it to converge
      towards a desired steady-state distribution. The proposed framework does not make
      any assumptions about the topology of the initial network, and is thus applicable
      to general-topology networks. We define the optimal perturbation control as the
      minimum-energy perturbation measured in terms of the Frobenius-norm between the
      initial and perturbed probability transition matrices of the dynamic network. We
      subsequently demonstrate that there exists at most one optimal perturbation that
      forces the network into the desirable steady-state distribution. In the event
      where the optimal perturbation does not exist, we construct a family of
      suboptimal perturbations, and show that the suboptimal perturbation can be used
      to approximate the optimal limiting distribution arbitrarily closely. Moreover,
      we investigate the robustness of the optimal perturbation control to errors in
      the probability transition matrix, and demonstrate that the proposed optimal
      perturbation control is robust to data and inference errors in the probability
      transition matrix of the initial network. Finally, we apply the proposed optimal
      perturbation control method to the Human melanoma gene regulatory network in
      order to force the network from an initial steady-state distribution associated
      with melanoma and into a desirable steady-state distribution corresponding to a
      benign cell.

PMID- 24027381
TI  - Approximate and Pseudo-Likelihood Analysis for Logistic Regression Using External
      Validation Data to Model Log Exposure.
AB  - A common goal in environmental epidemiologic studies is to undertake logistic
      regression modeling to associate a continuous measure of exposure with binary
      disease status, adjusting for covariates. A frequent complication is that
      exposure may only be measurable indirectly, through a collection of subject
      specific variables assumed associated with it. Motivated by a specific study to
      investigate the association between lung function and exposure to metal working
      fluids, we focus on a multiplicative-lognormal structural measurement error
      scenario and approaches to address it when external validation data are
      available. Conceptually, we emphasize the case in which true untransformed
      exposure is of interest in modeling disease status, but measurement error is
      additive on the log scale and thus multiplicative on the raw scale.
      Methodologically, we favor a pseudo-likelihood (PL) approach that exhibits fewer
      computational problems than direct full maximum likelihood (ML) yet maintains
      consistency under the assumed models without necessitating small exposure effects
      and/or small measurement error assumptions. Such assumptions are required by
      computationally convenient alternative methods like regression calibration (RC)
      and ML based on probit approximations. We summarize simulations demonstrating
      considerable potential for bias in the latter two approaches, while supporting
      the use of PL across a variety of scenarios. We also provide accessible
      strategies for obtaining adjusted standard errors to accompany RC and PL
      estimates.

PMID- 24027382
TI  - Tranexamic Acid: a recipe for saving lives in traumatic bleeding.

PMID- 24027383
TI  - Atypical localizations of hydatid disease: experience from a single institute.
AB  - INTRODUCTION: The hydatid disease most often involves the liver and the lungs.
      The disease can involve any part of the body except the hair, teeth and nails.
      Primary extrahepatico-pulmonary hydatid cysts are rare and only a few sporadic
      cases have been reported. MATERIALS AND METHODS: Two hundred and forty-four
      patients with hydatid cysts managed surgically from January 2005 to December 2009
      were evaluated retrospectively. Fourteen (5.7%) patients had isolated involvement
      of the atypical sites, while six (2.4%) also had a primary involvement of liver.
      RESULTS: The cysts were present in gall bladder (0.4%), peritoneum (1.6%), spleen
      (1.6%), ovary (0.4%), subcutaneous (0.8%), seminal vesicle (0.4%), spinal (0.4%),
      pancreas (0.4%), kidney (0.4%), mediastinal (0.4%), muscle (0.4%), and brain
      (0.8%). DISCUSSION AND CONCLUSIONS: Involvement of sites other than liver and
      lungs by hydatid disease is rare. Symptoms are related to size, location or
      possible complication of the cyst. It should be strongly suspected in
      differential diagnosis of all abdominal cysts especially in an endemic area.
      Proper surgical and medical management to avoid any recurrences, and a regular
      follow-up, are of utmost importance to detect any late complications such as
      local recurrence of the disease and development of hydatidosis at the primary
      sites.

PMID- 24027384
TI  - Chest injuries associated with head injury.
AB  - BACKGROUND: Although there have been significant advances in the management of
      traumatic brain injury (TBI), associated severe injuries, in particular chest
      injuries, remain a major challenge. This paper analyses the contribution of chest
      injuries to the outcome of head injuries in the University of Nigeria Teaching
      Hospital (UNTH) and the Memfys Hospital for Neurosurgery (MHN) in Enugu, Nigeria.
      MATERIALS AND METHODS: This is a retrospective review of the medical records,
      operative notes, and radiological findings of all patients admitted for head
      injury who had associated significant chest injuries in the MHN from 2002 to 2009
      and the UNTH between 2007 and 2010. Patients with only head injury and other
      extracranial injury not affecting the chest were excluded. Patients who were
      inadequately investigated were also excluded. RESULTS: Nineteen patients from the
      MHN and 11 patients from the UNTH were analyzed. Ages ranged from 9 to 65 years
      and the male:female ratio was 3:1. Injuries were most common between 30 and 50
      years and road traffic accident accounted for 60%. Barotrauma from ventilation
      was documented in 2 patients. The commonest types of intrathoracic injuries are
      pneumothorax and hemothorax. Chest wall injuries are more common but carry less
      morbidity and mortality. Only 20% of patients presented within 48 hours of
      injury. Management of the associated chest trauma commenced in the referring
      hospitals only in 26.4% of the patients. All patients with hemo-pneumothorax had
      tube thoracostomy as did 96% of patients with pneumothorax. 10% of patients with
      haemothorax needed thoracotomy. Mortality is 43%, which is higher than for
      patients with only TBI with comparable Glasgow coma scale. Outcome is influenced
      by the time to admission and the GCS on admission. CONCLUSION: Associated chest
      injuries result in higher mortality from head injuries. This association is more
      likely in the young and more productive. All patients presenting with head and
      spinal cord injury should be specifically and carefully evaluated for associated
      chest injuries. Computerized tomographic has not replaced the need for good
      quality chest radiograph in the emergency management of Head Injury associated
      chest trauma.

PMID- 24027386
TI  - Obstructive Jaundice Due to Tuberculosis of Distal CBD and Periampullary Region
      Mimickcholangiocarcinoma.
AB  - Abdominal tuberculosis (TB) commonly affects the intestinal tract, lymph nodes,
      peritoneum, and solid organs in varying combinations. Hepatobiliary or pancreatic
      TB is rare and the preoperative diagnosis is difficult. Though rare, there have
      been a few citations of intrahepatic tuberculosis, but isolated bile duct
      tuberculosis is extremely rare. Here we report a case of obstructive jaundice
      which was initially thought to be due to lower-end cholangiocarcinoma but
      postoperatively it was found to be tuberculosis. 

PMID- 24027385
TI  - Clinical features and pattern of presentation of breast diseases in surgical
      outpatient clinic of a suburban tertiary hospital in South-west Nigeria.
AB  - OBJECTIVE: To characterize the clinical features and pattern of presentation of
      breast diseases as observed in our practice. MATERIALS AND METHODS: A prospective
      study of 121 consecutive patients with breast complaints presenting in our
      Surgical Outpatient Clinics. The relevant data were collected by two surgeons
      using the prescribed forms and was analyzed using Epi Info 2003, Mann-Whitney
      (test of two groups) Chi-squared and Fishers exact test was used to compare
      parameters of benign and malignant groups. P value <0.05 was considered as
      significant. RESULTS: One hundred and nineteen patients were females, two were
      males. The age range was 14-70 years. Forty two (34.7%) patients were in the 21
      30 year age group. The commonest symptoms were breast lump in 111 (91.7%)
      patients, and breast pain in 28 (23.1%) patients. Breast pain was a significant
      presenting complaint in patients with breast malignancy (P=.026). On clinical
      examination 103 (85.1%) patients had palpable lumps, and seven patients were
      normal. Forty four patients (36.3%) had malignant disease, seventy patients
      (57.8%) had benign breast diseases and seven were normal. Fifty nine of the 70
      benign diseases were fibroadenoma. One hundred and three patients (85%) had
      appropriate therapy, while 18 patients (14.8%), including eight with malignant
      disease absconded. CONCLUSION: In the study, a breast lump was the commonest
      clinical feature of breast disease. Over 60% of these were benign. Breast pain
      was a statistically significant presentation in patients with malignant breast
      disease. One in seven of the patients absconded.

PMID- 24027387
TI  - Primary hydatid cyst in gastrocnemius muscle.
AB  - Cystic echinococcosis, which is caused by the larval stages of Echinococcus
      granulosus, results from the presence of one or more massive cysts or hydatids,
      and can involve any organ, including the liver, lungs, heart, brain, kidneys, and
      long bones. Muscle hydatidosis is usually secondary in nature, resulting from
      spread of larval tissue from a primary site after spontaneous or trauma-induced
      cyst rupture or after release of viable parasite material during invasive
      treatment procedures. Primary muscle hydatidosis is extremely uncommon, because
      implantation at this site would require passage through the filters of the liver
      and lung. Intramuscular hydatid cyst can cause a variety of diagnostic problems,
      especially in the absence of typical radiologic findings. We present an unusual
      case of a primary hydatid cyst found in the popliteal fossa of the right knee of
      a 52-year-old woman, presenting as an enlarging soft-tissue tumor for 6 months
      associated with pain. The mass initially was diagnosed to be Backer's cyst by
      ultrasonography, but later it was confirmed postoperatively through
      histopathological studies to be due to hydatid disease. In regions where
      hydatidosis is endemic, hydatid cyst should be included in the differential
      diagnosis of any unusual muscular mass. 

PMID- 24027388
TI  - Cold abscess of the anterior abdominal wall: an unusual primary presentation.
AB  - Tuberculosis is considered as ubiquitous disease as it involves any organ, but
      primary involvement of abdominal muscles is very rare. In most cases, the muscle
      involvement is secondary and is caused by either hematogenous route or direct
      inoculation from a tuberculous abdominal lymph node or extension from underlying
      tubercular synovitis and osteomyelitis. Autopsy studies have shown abdominal wall
      involvement in less than 1% of patients who died of tuberculosis. Antitubercular
      therapy is main form of management. Surgical intervention is always secondary in
      the form of either sonography or computerized tomography-guided aspiration or
      open drainage which is usually reserved for patients in whom medical treatment
      has failed. A case is hereby reported about primary tubercular anterior abdominal
      wall abscess without any evidence of pulmonary, skeletal or gastrointestinal
      tuberculosis in an apparently healthy individual with any past history of contact
      or previous antituberculosis therapy. 

PMID- 24027389
TI  - Secondary signet ring cell carcinoma of prostate.
AB  - True metastases to prostate from solid tumors are reported only in 0.2% of all
      surgical prostatic specimens and 2.9% of all male postmortems. Clinical context,
      morphological features, and immunohistochemical localization of prostate specific
      antigen (PSA) are supposed to clarify the differential diagnosis between a
      secondary and a primary tumor. We report an unusual and rare case of secondary
      signet ring cell carcinoma (SRCC) of prostate in which the clinical data and
      signet ring cell morphology pointed toward the diagnosis of a primary SRCC.
      Immunohistochemistry (IHC) for PSA not only proved the case to be a secondary
      SRCC but also initiated the process for diagnosis of the occult primary
      malignancy in the patient's stomach. 

PMID- 24027390
TI  - Migratory surgical gossypiboma-cause of iatrogenic perforation: case report with
      review of literature.
AB  - Forgotten foreign bodies, such as cotton sponges, gauze, or instruments, after
      any surgical procedure is considered a misadventure but avoidable complication.
      "Gossypiboma" denotes a mass of cotton that is accidentally retained in the body
      postoperatively. This study's goal was to systematically review the literature on
      retained sponges to identify incidence, site of occurrence, time of discovery,
      methods for detection, pathogenesis for intraluminal migration and risk factors.
      Author is reporting this case in which a 45-year old woman presented with
      features of chronic pain abdomen following abdominal hysterectomy (first surgery)
      which lead to open cholecystectomy (second surgery) after two and half year of
      first surgery. As patients continued to have persistent abdominal pain in spite
      of second surgery patient went to medical gastroenterologist who advised her
      series of tests including colonoscopy examination. The whole colon was normal on
      examination but on examination of terminal portion of small bowel some
      intraluminal mass was visualized. Attempt to retrieve this mass lead to
      iatrogenic ileal perforation. 

PMID- 24027391
TI  - Use of mitrofanoff and yang-monti techniques as ureteric substitution for severe
      schistosomal bilateral ureteric stricture: a case report and review of the
      literature.
AB  - Distal ureteric stricture is a common complication of urinary schistosomiasis
      which is a disease more prevalent in the tropics and subtropics. The surgical
      management of this complication is more challenging when it affects more than
      half of both ureters. We report the case of a 17-year-old Nigerian with a long
      standing recurrent painless terminal hematuria associated with bilateral colicky
      loin pains. Ultrasound scan showed bilateral hydro ureters and hydro nephrosis
      with deranged biochemical renal function. The patient had bilateral tube
      nephrostomy and antibiotic therapy. Definitive bilateral ureteric substitution
      was done using Mitrofanoff technique for the right ureter and Yang-Montie
      technique for the left ureter. The patient's renal function became normal and he
      was discharged home without complication. The related literatures were reviewed.
      Surgical nonurothelial ureteral substitution is necessary for long, extensive,
      severe bilateral ureteric strictures so as to prevent progressive renal damage
      and end stage renal failure. 

PMID- 24027392
TI  - Pre surgical evaluation of scrotal cystocele by conventional radiography
      (cystogram).
AB  - Urinary bladder is a known content of sliding inguinal hernias but rarely
      presents as irreducible direct inguinal hernia. As inguinal hernia repair is
      commonly undertaken even at peripheral surgical centers. Cystogram a simple
      radiological investigation (picturesque view) is useful for pre-surgical
      evaluation as it can prevent iatrogenic bladder injury during inguinal hernia
      repair. This investigation can be performed where other radiological expertises
      like computerized tomography scan/magnetic resonance imaging or even ultrasound
      facilities are not readily available. 

PMID- 24027393
TI  - Packing of renal fossa: useful technique for intractable bleeding after open
      pyelolithotomy surgery.
AB  - There is no documented study to indicate the role of prolonged packing of renal
      fossa (24 to 48 hours) to control bleeding in life threating haemorrhage
      following open pyelolithotomy without compromise in the renal functions. On the
      contrary emergency nephrectomy was performed for intractable bleeding during
      renal stone surgery in peripheral hospitals. Several studies have shown the
      usefulness of temporary packing to control bleeding in liver injuries and
      following open heart operations. Packing of the renal fossa with laparotomy pads
      in unstable patients, and transferring the patient to the surgical intensive care
      unit (ICU) is also described in trauma but not in controlling bleeding after open
      pyelolithotomy. This study comprises of three such patients whose kidneys were
      salvaged by a simple procedure of temporary packing of renal fossa for period of
      24-48 hours who had developed life threatening haemorrhage after open
      pyelolithotomy. This technique is simple and worth trying especially for surgeons
      who are contemplating nephrectomy as prolonged packing has not lead to any
      compromise in renal functions. The aim of this manuscript is very limited and
      clear. Packing is not a licence to carry out open pyelolithotomy without proper
      expertise and local backup or resources. Principles of safe and ethical surgical
      practice should never be violated as it can lead to medico legal complications. 

PMID- 24027394
TI  - Organ transplantation: legal, ethical and islamic perspective in Nigeria.
AB  - Organ transplantation dates back to the ancient times and since then it has
      become one of the important developments in modern medicine; saving the lives, as
      well as improving the quality of life of many patients. As the demand for organ
      transplantation far exceeds the organ availability, the transplant program is
      often saddled with complex legal and ethical issues. This review article
      highlights the legal and ethical issues that might arise regarding organ
      transplantation and appraises the existing legal frame work governing organ
      transplantation in Nigeria. Information on legal, cultural, religious and medical
      ethical issues regarding organ transplantation in Nigeria was obtained by
      searching the PubMed and Google Scholar, conference proceedings, seminar paper
      presentations, law library and other related publications were collated and
      analyzed. In decision making for organ transplantation, the bioethical principles
      like autonomy, beneficence and justice must be employed. It was believed by
      Catholic theologians that to mutilate one living person to benefit another
      violates the principle of Totality. Among Muslim scholars and researchers, there
      are those who throw legal support as to its permissibility while the other group
      sees it as illegal. Organ/tissues transplantation is considered a medical
      intervention that touches on the fundamental rights of the donor or the
      recipient. Where there is an unlawful infringement of the right of such persons
      in any way may be regarded as against Section 34 of the 1999 Nigerian
      Constitution dealing with right to dignity of the human person. Worldwide, the
      researchers and government bodies have agreed on informed consent for
      organ/tissue donation and for recipient should be obtained without coercion
      before embarking on such medical treatment Worldwide organ transplantation has
      become the best medical treatment for patients with end stage organ failure.
      However, there is no law/legislation backing organ/tissues transplantation in
      Nigeria. The government should take measures to combat transplantation tourism
      and the problem of national and international trafficking in human tissues and
      organs, ethics commission and National Transplant registry should be established
      in order to monitor and regulate the programme in the country. 

PMID- 24027395
TI  - Surgically treated symptomatic prolapsed lumbar and sacral intervertebral discs
      in females: a comparative study of incidence and causative factors and treatment.
AB  - BACKGROUND AND OBJECTIVE: There are various postulated possible causes of
      surgically symptomatic prolapsed intervertebral discs in the lumbar and sacral
      regions. They may be acting singularly or collectively. Yet, these factors, which
      could vary in different environments, have not been satisfactorily confirmed. The
      intention of this study is to share the experience of the author in the
      occurrence, possible causative factors, and treatment of surgically symptomatic
      prolapsed lumbar and sacral intervertebral discs in females, and to compare this
      experience in Switzerland, Nigeria, and Jamaica using surgery records for a
      period of over 39 years. MATERIALS AND METHODS: Records of these cases were
      examined and analyzed with the intent of comparing the frequency of occurrence
      and possible causative factors of this lesion in some countries. RESULTS: There
      were 60 locations in 51 patients in Basel (Caucasian population only), 4
      locations in 1 patient in Imo and Ebonyi States (African population only), and
      none in Jamaica (mixed population). The patients' ages ranged from 19 to 71 years
      in Switzerland, and the only patient in Nigeria was 49 years old. CONCLUSION: The
      study revealed that surgically treated symptomatic prolapsed lumbar and sacral
      intervertebral discs in females occurred more in Basel, Switzerland, than in Imo
      and Ebonyi States of Nigeria and none occurred in Jamaica, West Indies. Racial
      differences, certain sporting/recreational activities, smoking, and type of
      profession could have contributed to the development of this disease.

PMID- 24027396
TI  - Condylar disarticulation; analysis of 20 cases from a nigerian tertiary centre.
AB  - BACKGROUND: A disarticulation resection is a variant of mandibular segmental
      resection in which the condylar articulation is sacrificed. Indication varies
      from primary condylar lesions to jaw conditions involving the condyle. AIM: This
      retrospective analysis was carried out to highlight the pattern of
      disarticulation resections carried out in our centre over a five-year period.
      MATERIALS AND METHODS: Cases of mandibular resection were identified from the
      operation book. The medical records of patients who had disarticulation resection
      were then retrieved and analyzed for demography, indications for
      disarticulations, methods of reconstruction and complications. RESULTS: A total
      of 20 cases of disarticulation with complete records were obtained, this
      constituted 24.7% of total mandibular resections in the department. There were 9
      males and 11 females with a male: female ratio of 1:1.2. The age ranged between
      13 and 59 years with a mean of 30.4 years (std. 12.0). Sixteen patients received
      autogenous bone graft; two were stabilized using Steinman's pins and two with
      reconstruction plates. One bone graft and one reconstruction plate were removed
      because of infection and exteriorization respectively. Condyle was not replaced
      in any case. Outcomes were satisfactory but jaw deviation on opening was a common
      complaint in all cases. CONCLUSION: Condylar disarticulation accounts for a
      considerably high percentage of mandibular resection in our centre. Non
      vascularized immediate bone grafting without actual joint reconstruction was
      common. No disarticulation was carried out for traumatic reasons.

PMID- 24027397
TI  - Surgically correctable morbidity from male circumcision: indications for
      specialist surgical care in lagos.
AB  - AIM/OBJECTIVE: To determine the pattern of morbidity and outcome among patients
      referred to the Pediatric Surgery Unit of the Lagos University Teaching Hospital
      (LUTH) following circumcision. MATERIALS AND METHODS: Retrospective descriptive
      study of all patients with complications of circumcision who were managed in LUTH
      between 2008 and 2010. RESULTS: There were 36 patients. The age range was between
      2 days and 9 years (median-3 months). Fifteen cases (42.9%) were due to urethro
      cutaneous fistula while there were six cases (16.7%) of postcircumcision
      bleeding. There were four cases (11.1%) each of partial penile amputation and
      buried penis. There were also cases of meatal stenosis, penile implantation cyst
      and glanulo-preputial skin bridge. With respect to the treatment offered, eleven
      (30.6%) patients had urethroplasty for the urethro-cutaneous fistulae while seven
      (19.4%) patients had penile refashioning for the buried penis and penile
      amputation. Appropriate surgical treatments were performed for the other
      complications. CONCLUSION: Urethrocutaneous fistula and penile amputation are the
      commonest complications of circumcision for which referral is made to LUTH.
      Treatment outcome was satisfactory. Health education and legislation to ensure
      procedure is performed by qualified medical and paramedical staff may reduce the
      morbidity.

PMID- 24027398
TI  - ICU Cutilization by Cardio-Thoracic Patients in a Nigerian Teaching Hospital: Any
      Role for HDU?
AB  - BACKGROUND: The underlying pathological conditions in cardio-thoracic patients,
      anesthetic and operative interventions often lead to complex physiological
      interactions that necessitate ICU care. Our objectives were to determine the
      intensive care unit (ICU) utilization by cardio-thoracic patients in our centre,
      highlight the common indications for admission; and evaluate the interventions
      provided in the ICU and the factors that determined outcome. MATERIALS AND
      METHODS: The intensive care unit (ICU) records of University College Hospital,
      Ibadan for a period of 2 years (October 2007 to September 2009) were reviewed.
      Data of cardio-thoracic patients were extracted and used for analysis.
      Information obtained included the patient demographics, indications for
      admission, interventions offered in the ICU and the outcome. RESULTS: A total of
      1, 207 patients were managed in the ICU and 206 cardio-thoracic procedures were
      carried out during the study period. However, only 96 patients were admitted into
      the ICU following cardio-thoracic procedures, accounting for 7.9% of ICU
      admissions and 46.6% of cardio-thoracic procedures done within the review period.
      The mean length of stay and ventilation were 5.71 +/- 5.26 and 1.30 +/- 2.62
      days. The most significant predictor of outcome was endotracheal intubation (P =
      0.001) and overall mortality was 15%. CONCLUSION: There is a high utilization of
      the ICU by cardio-thoracic patients in our review and post-operative care was the
      main indication for admission. Some selected cases may be managed in the HDU to
      reduce the burden on ICU resources. We opine that when endotracheal intubation is
      to continue in the ICU, a 1:1 patient ratio should be instituted.

PMID- 24027399
TI  - Traumatic extradural hematoma in enugu, Nigeria.
AB  - AIM: Acute traumatic extradural hematoma (EDH) is life threatening and requires
      prompt intervention. This is a study of incidence and outcome of consecutive
      patients with EDH managed in Enugu, Nigeria against a background of delayed
      referral. MATERIALS AND METHODS: We retrospectively examined all consecutive
      trauma cases managed between 2003 and 2009 and analyzed patients with acute
      traumatic extradural hematoma in isolation or in combination with other intra
      cranial lesions. Age, sex, cause of injury, time of presentation, Glasgow Coma
      Score (GCS), pupil reactivity, treatment and clinical outcomes were determined.
      RESULTS: Of 817 head injuries, 69 (8.4%) had EDH, a mean of 9.9 patients per
      year. Males were 57 (83%) and females 12 (17%). Peak age incidences were the
      second and third decades of life, with a mean age of 30.2 years. Causes were road
      traffic accidents (57%), assault (22%) and falls (9%). Twenty-six (38%) patients
      presented within 24 h of injury and only one patient presented within 4 h. The
      average time lag before presentation was 94.2 h. At presentation 39% had GCS of
      13-15, 27% had 9-12 and 34% had 3-8. The most common location of hematoma was
      temporal (27.5%). Forty (59%) patients had surgery while 14 (20%) were managed
      conservatively. Ten patients (14.5%) died and of these 70% had GCS <8 and 60% had
      a seizure. CONCLUSION: We conclude that early appropriate treatment of EDH
      results in good high quality survival (Glasgow Outcome Score 4 or 5). Low GCS
      should not be an absolute contraindication for surgery. Seizure prophylaxis
      should be considered in patients with GCS <8.

PMID- 24027400
TI  - Anatomic variations in the palmar cutaneous branch of the median nerve among
      adults in Lagos, Nigeria.
AB  - Dysesthesias due to palmar cutaneous branch of median nerve injuries infrequently
      follow carpal tunnel release surgeries. OBJECTIVE: To determine the course of
      palmar cutaneous branch of the median nerve in wrist of adult Nigerians, identify
      the common variations, determine its relations to the palmaris longus (PL) in the
      region of the distal wrist crease. And on these basis, suggest a safe incision
      for carpal tunnel surgery in Nigerians. MATERIALS AND METHODS: Detailed anatomic
      dissection of the palmar cutaneous branch of the median nerve was carried out
      with the aid of a loupe magnification on 40 Nigerian cadaver wrists. The origin,
      course in the distal forearm, wrist and proximal palm was traced. Measurements of
      the distances between the radial and ulnar branches of the nerve and the PL were
      made. The distance between origin of the nerve and the distal wrist crease was
      measured as well. The common branching pattern of the nerve was noted. RESULTS:
      The palmar cutaneous branch of the median nerve was present in all dissected
      wrists. The mean distance of the radial branch to PL was 0.81 cm (SD +/- 0.3 cm),
      while the ulnar branch was 0.3 cm (SD +/- 0.1 cm). from same structure. The mean
      distance from the origin to the distal wrist crease is 4.5 cm (SD +/- 2.1 cm). We
      noted the terminal distal branching pattern of the nerve to be highly variable.
      CONCLUSION: The Palmar cutaneous branch of the median nerve is safe with an
      incision made at least 0.5 cm ulnar to the PL in carpal tunnel surgeries in
      Nigerians.

PMID- 24027401
TI  - Pattern of Assault-induced Oral and Maxillofacial Injuries in Ado-Ekiti, Nigeria.
AB  - BACKGROUND: Assault, though a major cause of maxillofacial injuries in the
      developed nations, has not been adequately investigated among Nigerian
      population. This study aimed to analyze the pattern of maxillofacial injuries
      caused by assault in our institution. METHODS: A descriptive clinical survey of
      patients with assault-induced oral and maxillofacial injuries presenting to our
      maxillofacial surgery clinic/emergency ward was carried out. Demographic data and
      pattern of injuries obtained from patients' record and department trauma database
      were analyzed. RESULTS: 156 patients presented with oral and maxillofacial
      injuries between October 2009 and December 2010. Thirty-four cases were due to
      assault and male to female ratio was 1.8:1. The mean age of the patients was
      21.4+/-6.26 years (age range 2-48 years). 23.6% (n=8) of the injuries were due to
      domestic violence between spouses while 35.3% (n=12) resulted from fight.
      Students unrest and armed robbery attack accounted for six cases each (17.7%,
      n=6), while there were two cases due to child battering. 64.3% (n=22) of the
      injuries sustained involved soft tissues while 35.7% involved hard tissues.
      Contusion was the most common isolated soft tissue injury accounting for 56%
      (n=10) while dentoalveolar fracture was the most encountered hard tissue injury
      (62.5%, n=16). CONCLUSION: There is need for preventive strategies to reduce the
      incidence of assault-induced maxillofacial injuries.

PMID- 24027402
TI  - Intratesticular varicocele.
AB  - We report case of a 28-year-old male who had extratesticular varicocele which was
      associated with intratesticular varicocele. The patient was referred to our
      department with pain in scrotal region. Routine scrotal sonography revealed
      extratesticular varicocele which was confirmed by color Doppler. It was
      associated with intratesticular varicocele. Intratesticular varicocele is a rare
      condition with a variable sonographic appearance. Color Doppler sonography is
      helpful in confirming the diagnosis. Detection of intratesticular component is
      essential in the management of varicoceles. 

PMID- 24027403
TI  - Diaphragmatic hernia masquerading as pleural effusion.
AB  - Rupture of the diaphragm is almost always due to major trauma. We present here an
      unusual and rare case of late presentation of diaphragmatic hernia after an
      innocuous injury. The patient was initially misdiagnosed as a left pleural
      effusion on the basis of chest X-ray and ultrasound findings. Finally, the
      diagnosis was confirmed on computerized scanning. 

PMID- 24027404
TI  - An uncommon cause of acute bowel obstruction: the left para-duodenal hernia.
AB  - Internal hernias of the abdomen are uncommon. They represent less than 1% of
      bowel obstruction cases. The left Paraduodenal hernia (PH) is the most frequent
      type of internal hernias. We report a case of 77 year- old woman consulting for
      bowel obstruction evolving since two days. The abdominal computed tomography
      revealed a retroperitoneal small bowel contained in a peritoneal sac. The
      surgical exploration confirmed the diagnosis of a left internal PH by showing
      incarcerated jejunal loops in a PH through a narrow opening to the left of the
      angle of Treitz. A surgical reduction of the hernia and closure of the hernia
      neck were performed. The follow-ups were uncomplicated. Through this observation
      and a literature review, we try to recall the clinical and radiological
      characteristics of this disease and to clarify the therapeutic modalities. 

PMID- 24027405
TI  - Primary Peritoneal Hydatidosis in a 76-Year-Old Farmer: An Unusual form of a
      Common Disease.
AB  - A 76-year-old farmer presented at our emergency unit with a history of gradual
      swelling of abdomen without fever, nausea, or urticaria. On examination there was
      symmetrical enlargement of abdomen with fluid thrill. Contrast-enhanced computed
      tomography scan showed that the entire peritoneal cavity was distended and
      occupied by multiloculated noncalcified content of mixed attenuations. Diagnosis
      of peritoneal seeding of hydatid cyst was made. At laparotomy, about 25 l of
      daughter cysts and a membrane was found in the peritoneal cavity without other
      organ involvement. Postoperative period was uneventful. 

PMID- 24027407
TI  - Intravenous leiomyomatosis.
AB  - Leiomyomas are benign tumors arising from smooth muscle of the uterus.
      Intravenous leiomyomatosis is characterized by intraluminal growth of benign
      smooth muscle into either venous or lymphatic vessels outside the limits of
      myoma. It commonly extends into the pelvic veins and manifests as worm-like
      protrusions of tumor emanating from veins at the parametrial margins of
      hysterectomy specimen. The tumor can cause life-threatening symptoms if it
      involves inferior vena cava or right atrium. We report a case of intravenous
      leiomyomatosis of the uterus managed at our institution. 

PMID- 24027406
TI  - Parietal wall hydatid cyst presenting as a primary lesion.
AB  - Hydatid cyst is the disease of liver and lungs and is common in some regions
      especially sheep rearing countries of the world, but this disease may occur in
      any part of world and anywhere in the body. This report presents primary hydatid
      cysts located in intramuscular region of left side of the abdomen. A 54-year-old
      female patient from central India, farmer by occupation, non vegetarian by diet
      came with chief complaints of a painless mass in the left iliac fossa, gradually
      increasing in size over a period of 6 months. Superficial ultrasound revealed a
      lesion resembling a hydatid cyst. Surgical excision was done without injuring the
      cyst. Diagnosis was confirmed on histo-pathological examination and was
      compatible with a hydatidcyst. Ahydatid cyst should be considered in the
      differential diagnosis of subcutaneouscystic lesions, it should be excised
      totally, with an intact wall and postoperative albendazole should be given to
      avoid recurrence. 

PMID- 24027408
TI  - Circumcision: experience at a private hospital in jos, Nigeria.
AB  - BACKGROUND: Most circumcisions in our environment are carried out in children for
      religious and cultural reasons. The PlastiBell device has been used for several
      decades, though some complications have been associated with its use. AIMS AND
      OBJECTIVES: This study examines the safety and acceptability of the PlastiBell
      device, which was used in circumcision in the majority of patients studied.
      MATERIALS AND METHODS: Fifty consecutive patients, who had circumcision at a
      private medical facility in Jos, Nigeria, over a 2 year period, were reported.
      Their ages, method of circumcision, size of PlastiBell device used, incidence of
      complications and acceptability of procedure to parents were documented. RESULTS:
      In this study, all patients below 42 days old had their circumcision done with
      the PlastiBell device. Complications seen with this device included hemorrhage in
      one patient following a slipped out device. In 49 (98%) of the patients, the
      mothers were satisfied with the outcome of the procedures. CONCLUSION: The
      PlastiBell device can be safely used for circumcisions in children below 42 days
      old.

PMID- 24027409
TI  - Pattern and survival of biliary atresia patients; experience in southern Nigeria.
AB  - BACKGROUND: Biliary atresia (BA) has been a challenge to surgeons worldwide.
      Beyond the revolutionary surgical technique popularised by Kasai, liver
      transplantation has added renewed hope in the long-term outcome. In Nigeria,
      where late presentation is very common, there is need to assess the long-term
      results of the treatment options available to us. AIM: We aimed to evaluate the
      presentation and management outcome of BA and the long-term survival of BA
      patients seen in our practice. MATERIALS AND METHODS: Cases of BA seen between
      January 2007 and December 2011 in three tertiary health facilities in South East
      Nigeria were included. Data obtained included age at presentation, clinical
      features, treatment offered and age at the time of death. Analysis was with the
      SPSS 17.0. RESULTS: Twenty four patients comprising 10 (41.7%) males and 14
      (58.3%) females were included in the study. The mean age of presentation was 4.02
      (+/-214) months; range 1.75-11.0 months. Fifteen (62.5%) patients had surgery
      while 9 (37.5%) received medical treatment only. The mean age at death was 14.2
      (+/-8.1) months; range 2.5-30 months. CONCLUSION: BA poses a daunting challenge
      in our practice. Outcome of treatment is still discouraging. We identified late
      presentation, lack of facilities to make early diagnosis, lack of adequately
      trained manpower to manage these children and lack of post-operative care and
      support for patients as the major challenges in the management of BA children in
      our region.

PMID- 24027410
TI  - Investigation of Infant Brain with or without Hydrocephalous in Our Environment
      Using Anterior Transfontanelle Ultrasound Scan.
AB  - AIM: A prospective study aimed to suggest easy and simple reproducible
      ventricular site that will be basic measurement plane and normal dimension
      determined, correlated to sizes of infants for comparative evaluation of
      hydrocephalous infants and should be reproducible in follow-up. MATERIALS AND
      METHODS: A prospective study done in University of Benin Teaching Hospital Benin,
      Nigeria. This study used 50 consecutive infants with Ultrasound scan (US)
      diagnosis of hydrocephalus and a control group of 50 US normal from 1(st) January
      2007 to 30(th) June 2008. The infants were scan through the mid-patent anterior
      fontanelle in sagittal, and transverse planes with minor angulations to properly
      outline the ventricles and the position of measurement determined at the foramen
      of Monro of lateral ventricles and the diameter measured. The infants' weight,
      crown-heel length, and head circumference were measured and body mass index (BMI)
      calculated and correlated to lateral ventricular measurement. Data analysis was
      conducted using the Statistical Package for Social Sciences (SPSS Inc, USA),
      Version 11.0. RESULTS: There was no statistically sex and age-related difference.
      There is statistically comparative high mean weight and height and lower BMI in
      hydrocephalic infants as against the control group (P < 0.001). The mean head
      circumference for hydrocephalus was 45.6 (+/- 10.5 standard deviation [SD]),
      whereas the control group was 35.9 (+/- 2.7 SD) with P < 0.001. The mean diameter
      of the anterior horn of left and right lateral ventricles at the level of foramen
      of Monro in hydrocephalic subjects is 18.4 mm +/- 14.3 mm and 20.1 mm +/- 16.8 mm
      with median diameter of 14.1 mm and 15.2 mm, respectively, whereas control group
      is 2.5 mm +/- 0.6 mm and 2.5 mm +/- 0.7 mm with median diameter of 2.5 mm and 2.4
      mm, respectively. CONCLUSION: Transfontanelle US was found highly useful in
      investigation of hydrocephalous in infant.

PMID- 24027411
TI  - Perforated duodenal ulcer; management in a resource poor, semi-urban nigerian
      hospital.
AB  - INTRODUCTION: Perforated duodenal ulcer (PDU) is still seen frequently in the
      study center inspite of the free use of effective medical curative therapy. We
      then set out to ascertain the pattern of presentation, peculiar risk factors in
      the study environment, re-evaluate our method of management, and to see if it is
      adequate for patients in a developing country. MATERIALS AND METHODS: This is a
      retrospective study of patients admitted and managed for PDUs, between January
      2004 and December 2011 at the Federal Medical Centre, IdoEkiti, Southwest
      Nigeria. The records of patients were retrieved and demographic data relating to
      age, sex, symptoms, duration, diagnosis, intra-operative findings, and management
      outcome were extracted. The results were analyzed. RESULTS: A total of 30
      patients were admitted and operated during this period. Twenty-eight of them were
      males and two were females. The mean age was 47 years and the male: female ratio
      was 14:1. The duration of symptoms before presentation ranged from 2 to 7 days.
      None of the patients had a prior diagnosis of their ulcers, by an upper gastro
      intestinal endoscopy before presentation; although most had dyspeptic symptoms,
      with inadequate or no medical treatment. The notable peculiar risk factor was the
      abuse of local herbal concoction for body pains by all the patients. Seven
      patients smokes, 15 consumes alcohol, and only two take non-steroidal anti
      inflammatory drugs for body pains. Most of the managed patients; 26 were
      satisfactorily discharged home and later followed-up at the surgical out-patient
      department. Four mortality was recorded during the period of study. CONCLUSION:
      PDU is still a major complication of chronic peptic ulcer disease. Simple omental
      patch and H. pylori eradication is no longer appropriate as a mode of treatment
      for the youths who are mostly affected in the center. We therefore, suggest a
      more wide spread use of definitive ulcer surgery for most of our patients with no
      pre-operative risk factors.

PMID- 24027412
TI  - Intent at day case laparoscopic cholecystectomy in owerri, Nigeria: initial
      experiences.
AB  - BACKGROUND AND OBJECTIVE: Laparoscopic cholecystectomy has been the default
      operation for cholelithiasis at Federal Medical Centre, Owerri for the past 2
      years and the outcomes have been good. The duration of post operative stay has
      been decreasing. We therefore initiated a preliminary 2-year prospective study in
      May 2010 to determine the feasibility of carrying out day case laparoscopic
      cholecystectomy in our hospital. MATERIALS AND METHODS: PATIENTS UNDERGOING
      LAPAROSCOPIC CHOLECYSTECTOMY WERE INCLUDED IN THE STUDY IF THEY SATISFIED THE
      FOLLOWING CRITERIA: Age < 65 years, body mass index < 35 kg/m(2) , American
      Society of Anaesthesiology physical status class I and II, patient residence
      within 20 km radius of the hospital, patient acceptance of the procedure and
      absence of previous complicated upper abdominal surgery. RESULTS: Twelve patients
      (10 females, 2 males) were worked up with the intent of achieving same-day
      discharge of the patients. Five of the patients (41.7%) were discharged on the
      day of operation. The reasons for overnight stay included inadequate pain
      control, insertion of drain and patient wishes. There was no conversion to open
      surgery, no major complications and no case of readmission to the hospital.
      CONCLUSIONS: Day case laparoscopic cholecystectomy in our environment could be
      safely promoted but will depend on improved facilities and patient enlightenment.

PMID- 24027413
TI  - Time of passage of First Stool in Newborns in a Tertiary Health Facility in
      Southern Nigeria.
AB  - INTRODUCTION: The first stool passed by the newborn, the meconium, is different
      from the ordinary stool both in its nature and its implication. Delayed or non
      passage of the meconium may represent a number of clinical conditions. In this
      study, we sought to identify what should be considered delayed passage of
      meconium in our babies. AIMS AND OBJECTIVES: To investigate the timing of passage
      of first stool in Nigerian neonates and whether it is influenced by gender, birth
      weight, maternal age, and parity. MATERIALS AND METHODS: A PROFORMA WAS DESIGNED
      TO OBTAIN THE FOLLOWING DATA: Maternal age, parity, mode of delivery, Apgar score
      at 1 min, birth weight, gender, and interval between delivery and passage of
      first stool among normal newborn babies delivered at the obstetrics department of
      our center in August and September 2010. RESULTS: One hundred babies out of 393
      delivered during the period of the study were included in the study. There were
      63 (63%) males and 37 (37%) females. The interval between delivery and passage of
      meconium ranged from 0.5 to 54 h; mean, 16.2 (SD = 10.57). This was not
      influenced by gender, weight, maternal age, and parity. CONCLUSION: Non-passage
      of meconium beyond 48 h of life could be considered delayed. We therefore,
      recommend that clinicians should re-evaluate newborns, for hitherto unrecognized
      conditions, if after 48 h they have not passed first stool.

PMID- 24027414
TI  - The place of spermatic fascia closure during open herniotomy in male children.
AB  - INTRODUCTION: There is currently no consensus about closing or otherwise of the
      spermatic fascia at herniotomy in children. This stems from lack of evidence to
      justify either stand, and most literatures are silent on this. This study is an
      effort to evaluate the place of closure of the spermatic fascia at hernia repair.
      AIM: To determine if there is advantage in closing the spermatic fascia over
      leaving it open during herniotomy in children. MATERIALS AND METHODS: Cases of
      inguinoscrotal hernia repaired by the same surgeon between July 2009 and June
      2011 were randomly grouped into two; spermatic fascia closed (SC) and spermatic
      fascia open (SO) groups. They were assessed for operation duration, wound
      infection, scrotal hematoma, and scrotal edema post repair. The Data obtained was
      collated and analyzed using the SPSS 17.0. RESULTS: Seventy-six male children
      with unilateral complete inguinoscrotal hernia were included in this study. The
      overall mean duration of operation was 32.9 min (SD = 5.7); range 21-52 min.
      There was hematoma formation in 7 (17.9%) of the SC group and 9 (24.3%) of the SO
      group (P = 0.5). Scrotal edema occurred in 24 (64.8%) of the SO and 18 (46.2%) of
      the SC group (P = 0.3). No other complications were recorded during the period of
      study. CONCLUSION: There is no demonstrable advantage or disadvantage in closing
      the spermatic fascia at herniotomy for children. We conclude that the choice to
      close or not to close the spermatic fascia at herniotomy for children should be
      at the discretion of the individual surgeon.

PMID- 24027415
TI  - Clinico-pathological Correlation of Digital Rectal Examination Findings Amongst
      Nigerian Men with Prostatic Diseases: A Prospective Study of 236 Cases.
AB  - AIMS AND OBJECTIVE: This study aims at correlating different digital rectal
      examination (DRE) abnormalities with histopathological results in patients with
      prostatic diseases. MATERIALS AND METHODS: A prospective study of 236 patients
      who underwent prostate needle biopsy (PNB). Inclusion criteria were presence of
      abnormal DRE findings or elevated prostate specific antigen above 4 ng/ml or
      both. They all had 10-core extended transrectal biopsy and specimens were sent
      for histopathological examination. Correlations were made between DRE findings
      and histopathology results. Two separate multivariate logistic regression models
      were created; the first evaluated the relationship of predictors (DRE findings)
      to the likelihood of detecting cancer and the second explored predictors of high
      grade cancer on PNB. RESULTS: Two hundred and thirty-six patients were enrolled
      with a mean age of 66.9 years and range of 43-90 years. Histopathology results
      were malignant in 102 (43.2%) and benign in 134 (56.8%). Ninety-one (38.6%) and
      145 (61.4%) had normal DRE and abnormal DRE findings with cancer detection rates
      of 23.1% and 55.8% respectively. Nodular prostate is the most common abnormality
      in 63.4% patients with abnormal DRE. Each sign of DRE had different predictive
      value with enhanced positive predictive value when combinations of abnormalities
      are present. Abnormal DRE is an independent predictor of high-grade tumor. Mean
      Gleason scores were 4.7 and 7.1 in patients with normal and abnormal DRE
      respectively. CONCLUSION: DRE is a useful and important tool in assessing
      patients with suspected prostate diseases who need prostate biopsy. An abnormal
      DRE correlated well with prostate cancer and independently predicted high-grade
      disease in these men.

PMID- 24027416
TI  - Myxoid neurothekeoma: a rare soft tissue tumor of hand in a male toddler.
AB  - Neurothekeomas are rare benign neoplasms, typically occurring in young patients
      with a remarkable predilection for the female population. Patients usually
      present with a small nodule in different anatomical sites, commonly involving the
      face and the upper limb. We report a case of a three-year-old boy, who presented
      with a nontender nodule on the left thumb. Surgical biopsy and immunostaining
      confirmed the diagnosis as myxoid neurothekeoma. The rarity of this unusual skin
      tumor in a toddler prompted the following report. 

PMID- 24027417
TI  - POPBAM: Tools for Evolutionary Analysis of Short Read Sequence Alignments.
AB  - BACKGROUND: While many bioinformatics tools currently exist for assembling and
      discovering variants from next-generation sequence data, there are very few tools
      available for performing evolutionary analyses from these data. Evolutionary and
      population genomics studies hold great promise for providing valuable insights
      into natural selection, the effect of mutations on phenotypes, and the origin of
      species. Thus, there is a need for an extensible and flexible computational tool
      that can function into a growing number of evolutionary bioinformatics pipelines.
      RESULTS: This paper describes the POPBAM software, which is a comprehensive set
      of computational tools for evolutionary analysis of whole-genome alignments
      consisting of multiple individuals, from multiple populations or species. POPBAM
      works directly from BAM-formatted assembly files, calls variant sites, and
      calculates a variety of commonly used evolutionary sequence statistics. POPBAM is
      designed primarily to perform analyses in sliding windows across chromosomes or
      scaffolds. POPBAM accurately measures nucleotide diversity, population
      divergence, linkage disequilibrium, and the frequency spectrum of mutations from
      two or more populations. POPBAM can also produce phylogenetic trees of all
      samples in a BAM file. Finally, I demonstrate that the implementation of POPBAM
      is both fast and memory-efficient, and also can feasibly scale to the analysis of
      large BAM files with many individuals and populations. Software: The POPBAM
      program is written in C/C++ and is available from
      http://dgarriga.github.io/POPBAM. The program has few dependencies and can be
      built on a variety of Linux platforms. The program is open-source and users are
      encouraged to participate in the development of this resource.

PMID- 24027418
TI  - SBEToolbox: A Matlab Toolbox for Biological Network Analysis.
AB  - We present SBEToolbox (Systems Biology and Evolution Toolbox), an open-source
      Matlab toolbox for biological network analysis. It takes a network file as input,
      calculates a variety of centralities and topological metrics, clusters nodes into
      modules, and displays the network using different graph layout algorithms.
      Straightforward implementation and the inclusion of high-level functions allow
      the functionality to be easily extended or tailored through developing custom
      plugins. SBEGUI, a menu-driven graphical user interface (GUI) of SBEToolbox,
      enables easy access to various network and graph algorithms for programmers and
      non-programmers alike. All source code and sample data are freely available at
      https://github.com/biocoder/SBEToolbox/releases. 

PMID- 24027419
TI  - Hsp60 chaperonin acts as barrier to pharmacologically induced oxidative stress
      mediated apoptosis in tumor cells with differential stress response.
AB  - Mitochondrial functions play a central role in energy metabolism and provide
      survival fitness to both normal and tumor cells. Mitochondrial chaperonin Hsp60
      is involved in both pro- and anti-apoptotic functions, but how Hsp60 senses the
      mitochondria selective oxidative stress response is unknown. In this study, by
      using rotenone, an irreversible inhibitor of oxidative phosphorylation against
      IMR-32 and BC-8 tumor cells containing differential heat shock transcriptional
      machinery, we studied whether the oxidative stress response is related to Hsp60.
      The accelerated cytotoxicity in response to rotenone has been correlated with
      enhanced production of O2 (*-), H2O2, reactive oxygen species, and Hsp60
      translocation from the mitochondria to the cytoplasm. The inability of cells to
      resist oxidative stress mediated Hsp60 translocation appeared to depend on
      mitochondrial oxyradical scavenging system and Bax translocation. A delayed
      oxidative stress response in hsp60 shRNA-treated cells was found to be due to
      increased mitochondrial translocation of Hsp60 on shRNA pre-sensitization.
      Overexpression of Hsp60 failed to protect cells from oxidative stress due to a
      lack of its mitochondrial retention upon post-rotenone treatment. These results
      also revealed that Hsp60 mitochondrial localization is indispensable for
      decreasing O2 (*-) levels, but not H2O2 and ROS levels. However, cycloheximide
      treatment alone induced Hsp60 translocation, while rotenone combination delayed
      this translocation. In contrast to oxidative stress, MG132 and 17AAG treatments
      showed mitochondrial retention of Hsp60; however, MG132 combination either with
      hsp60 shRNA or 17AAG induced its translocation. Additionally, overexpression of
      Huntingtin gene also resulted in Hsp60 mitochondrial accumulation. We suggest
      that Hsp60 may act as a barrier to pharmacological targeting of mitochondria. 

PMID- 24027420
TI  - Molecular Modeling of Differentially Phosphorylated Serine 10 and Acetylated
      lysine 9/14 of Histone H3 Regulates their Interactions with 14-3-3zeta, MSK1, and
      MKP1.
AB  - Histone modifications occur in precise patterns, with several modifications known
      to affect the binding of proteins. These interactions affect the chromatin
      structure, gene regulation, and cell cycle events. The dual modifications on the
      H3 tail, serine10 phosphorylation, and lysine14 acetylation (H3Ser10PLys14Ac) are
      reported to be crucial for interaction with 14-3-3zeta. However, the mechanism by
      which H3Ser10P along with neighboring site-specific acetylation(s) is targeted by
      its regulatory proteins, including kinase and phosphatase, is not fully
      understood. We carried out molecular modeling studies to understand the
      interaction of 14-3-3zeta, and its regulatory proteins, mitogen-activated protein
      kinase phosphatase-1 (MKP1), and mitogen- and stress-activated protein kinase-1
      (MSK1) with phosphorylated H3Ser10 alone or in combination with acetylated H3Lys9
      and Lys14. In silico molecular association studies suggested that acetylated
      Lys14 and phosphorylated Ser10 of H3 shows the highest binding affinity towards
      14-3-3zeta. In addition, acetylation of H3Lys9 along with Ser10PLys14Ac favors
      the interaction of the phosphatase, MKP1, for dephosphorylation of H3Ser10P.
      Further, MAP kinase, MSK1 phosphorylates the unmodified H3Ser10 containing N
      terminal tail with maximum affinity compared to the N-terminal tail with
      H3Lys9AcLys14Ac. The data clearly suggest that opposing enzymatic activity of
      MSK1 and MKP1 corroborates with non-acetylated and acetylated, H3Lys9Lys14,
      respectively. Our in silico data highlights that site-specific phosphorylation
      (H3Ser10P) and acetylation (H3Lys9 and H3Lys14) of H3 are essential for the
      interaction with their regulatory proteins (MKP1, MSK1, and 14-3-3zeta) and plays
      a major role in the regulation of chromatin structure. 

PMID- 24027421
TI  - US-Approved Intra-Articular Hyaluronic Acid Injections are Safe and Effective in
      Patients with Knee Osteoarthritis: Systematic Review and Meta-Analysis of
      Randomized, Saline-Controlled Trials.
AB  - We conducted a systematic review and meta-analysis of randomized saline
      controlled trials to determine the safety and efficacy of US-approved intra
      articular hyaluronic acid (IAHA) injections for symptomatic knee osteoarthritis.
      A total of 29 studies representing 4,866 unique subjects (IAHA: 2,673, saline:
      2,193) were included. IAHA injection resulted in very large treatment effects
      between 4 and 26 weeks for knee pain and function compared to pre-injection
      values, with standardized mean difference (SMD) values ranging from 1.07-1.37
      (all P < 0.001). Compared to saline controls, SMDs with IAHA ranged from 0.38
      0.43 for knee pain and 0.32-0.34 for knee function (all P < 0.001). There were no
      statistically significant differences between IAHA and saline controls for any
      safety outcome, including serious adverse events (SAEs) (P = 0.12), treatment
      related SAEs (P = 1.0), study withdrawal (P = 1.0), and AE-related study
      withdrawal (P = 0.46). We conclude that intra-articular injection of US-approved
      HA products is safe and efficacious in patients with symptomatic knee
      osteoarthritis. 

PMID- 24027422
TI  - Crime and violence in Brazil: Systematic review of time trends, prevalence rates
      and risk factors.
AB  - Between 1980 and 2010 there were 1 million homicides in Brazil. Dramatic
      increases in homicide rates followed rises in inequality, more young men in the
      population, greater availability of firearms, and increased drug use.
      Nevertheless, disarmament legislation may have helped reduce homicide rates in
      recent years. Despite its very high rate of lethal violence, Brazil appears to
      have similar levels of general criminal victimization as several other Latin
      American and North American countries. Brazil has lower rates of drug use
      compared to other countries such as the United States, but the prevalence of
      youth drug use in Brazil has increased substantially in recent years. Since 1990,
      the growth of the Brazilian prison population has been enormous, resulting in the
      fourth largest prison population in the world. Through a systematic review of the
      literature, we identified 10 studies assessing the prevalence of self-reported
      offending in Brazil and 9 studies examining risk factors. Levels of self-reported
      offending seem quite high among school students in Brazil. Individual and family
      level risk factors identified in Brazil are very similar to those found in high
      income countries.

PMID- 24027423
TI  - Higher-order structure of nucleic acids in the gas phase: top-down analysis of
      base-pairing interactions.
AB  - Non-ergodic as well as ergodic activation methods are capable of maintaining the
      integrity of base pairs during the top-down analysis of nucleic acids. Here, we
      investigate the significance of this characteristic in the investigation of
      higher-order structures of increasing complexity. We show that cognate fragments
      produced by typical backbone cleavages may not be always detected as separate
      sequence ions, but rather as individual products that remain associated through
      mutual pairing contacts. This effect translates into unintended masking of
      cleavage events that take place in double-stranded regions, thus leading to the
      preferential detection of fragments originating from unpaired regions. Such
      effect is determined by the stability of the weak non-covalent association
      between complementary stretches, which is affected by base composition, length of
      the double-stranded structure, and charge of the precursor ion selected for
      analysis. Although such effect may prevent the achievement of full sequence
      coverage for primary structure determination, it may provide the key to correctly
      differentiate double- versus single-stranded regions, in what could be defined as
      gas-phase footprinting experiments. In light of the critical role played by base
      pairs in defining the higher-order structure of nucleic acids, these approaches
      will be expected to support an increased utilization of mass spectrometry for the
      investigation of nucleic acid structure and dynamics.

PMID- 24027424
TI  - Dyadic Flexibility in Early Parent-Child Interactions: Relations with Maternal
      Depressive Symptoms and Child Negativity and Behaviour Problems.
AB  - Lower levels of parent-child affective flexibility indicate risk for children's
      problem outcomes. This short-term longitudinal study examined whether maternal
      depressive symptoms were related to lower levels of dyadic affective flexibility
      and positive affective content in mother-child problem-solving interactions at
      age 3.5 years (N=100) and whether these maternal and dyadic factors predicted
      child emotional negativity and behaviour problems at a 4-month follow-up. Dyadic
      flexibility and positive affect were measured using dynamic systems-based
      modelling of second-by-second affective patterns during a mother-child problem
      solving task. Results showed that higher levels of maternal depressive symptoms
      were related to lower levels of dyadic affective flexibility, which predicted
      children's higher levels of negativity and behaviour problems as rated by
      teachers. Mothers' ratings of child negativity and behaviour problems were
      predicted by their own depressive symptoms and individual child factors, but not
      by dyadic flexibility. There were no effects of dyadic positive affect. Findings
      highlight the importance of studying patterns in real-time dyadic parent-child
      interactions as potential mechanisms of risk in developmental psychopathology.

PMID- 24027425
TI  - STAT3 in epithelial cells regulates inflammation and tumor progression to
      malignant state in colon.
AB  - Chronic inflammation is an important risk factor for the development of
      colorectal cancer; however, the mechanism of tumorigenesis especially tumor
      progression to malignancy in the inflamed colon is still unclear. Our study shows
      that epithelial signal transducer and activator of transcription 3 (STAT3),
      persistently activated in inflamed colon, is not required for inflammation
      induced epithelial overproliferation and the development of early-stage tumors;
      however, it is essential for tumor progression to advanced malignancy. We found
      that one of the mechanisms that epithelial STAT3 regulates in tumor progression
      might be to modify leukocytic infiltration in the large intestine. Activation of
      epithelial STAT3 promotes the infiltration of the CD8+ lymphocyte population but
      inhibits the recruitment of regulatory T (Treg) lymphocytes. The loss of Stat3 in
      epithelial cells promoted the expression of cytokines/chemokines including CCL19,
      CCL28, and RANTES, which are known to be able to recruit Treg lymphocytes. Linked
      to these changes was the pathway mediated by sphingosine 1-phosphate receptor 1
      and sphingosine 1-phosphate kinases, which is activated in colonic epithelial
      cells in inflamed colon with functional STAT3 but not in epithelial cells deleted
      of STAT3. Our data suggest that epithelial STAT3 plays a critical role in
      inflammation-induced tumor progression through regulation of leukocytic
      recruitment especially the infiltration of Treg cells in the large intestine.

PMID- 24027426
TI  - AR variant ARv567es induces carcinogenesis in a novel transgenic mouse model of
      prostate cancer.
AB  - Androgen deprivation therapy remains the primary treatment modality for patients
      with metastatic prostate cancer but is uniformly marked by progression to
      castration-resistant prostate cancer (CRPC) after a period of regression.
      Continued activation of androgen receptor (AR) signaling is attributed as one of
      the most important mechanisms underlying failure of therapy. Recently, the
      discovery of constitutively active AR splice variants (AR-Vs) adds more credence
      to this idea. Expression of AR-Vs in metastases portends a rapid progression of
      the tumor. However, the precise role of the AR-Vs in CRPC still remains unknown.
      ARv567es is one of the two AR variants frequently found in human CRPC xenografts
      and metastases. Herein, we developed a probasin (Pb) promoter-driven ARv567es
      transgenic mouse, Pb-ARv567es, to evaluate the role of ARv567es in both
      autonomous prostate growth and progression to CRPC. We found that expression of
      ARv567es in the prostate results in epithelial hyperplasia by 16 weeks and
      invasive adenocarcinoma is evident by 1 year of age. The underlying genetic
      cellular events involved a cell cycle-related transcriptome and differential
      expression of a spectrum of genes that are critical for tumor initiation and
      progression. These findings indicate that ARv567es could induce tumorigenesis de
      novo and signifies the critical role of AR-Vs in CRPC. Thus, the Pb-ARv567es
      mouse could provide a novel model in which the role of AR variants in prostate
      cancer progression can be examined.

PMID- 24027427
TI  - Chemopreventive effects of the p53-modulating agents CP-31398 and Prima-1 in
      tobacco carcinogen-induced lung tumorigenesis in A/J mice.
AB  - Lung cancer is the leading cause of cancer deaths worldwide. Expression of the
      p53 tumor suppressor protein is frequently altered in tobacco-associated lung
      cancers. We studied chemopreventive effects of p53-modulating agents, namely, CP
      31398 and Prima-1, on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)
      induced lung adenoma and adenocarcinoma formation in female A/J mice. Seven-week
      old mice were treated with a single dose of NNK (10 umol/mouse) by
      intraperitoneal injection and, 3 weeks later, were randomized to mice fed a
      control diet or experimental diets containing 50 or 100 ppm CP-31398 or 150 or
      300 ppm Prima-1 for either 17 weeks (10 mice/group) or 34 weeks (15 mice/group)
      to assess the efficacy against lung adenoma and adenocarcinoma. Dietary feeding
      of 50 or 100 ppm CP-31398 significantly suppressed (P < .0001) lung
      adenocarcinoma by 64% and 73%, respectively, after 17 weeks and by 47% and 56%,
      respectively, after 34 weeks. Similarly, 150 or 300 ppm Prima-1 significantly
      suppressed (P < .0001) lung adenocarcinoma formation by 56% and 62%,
      respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks.
      Importantly, these results suggest that both p53 modulators cause a delay in the
      progression of adenoma to adenocarcinoma. Immunohistochemical analysis of lung
      tumors from mice exposed to p53-modulating agents showed a significantly reduced
      tumor cell proliferation and increased accumulation of wild-type p53 in the
      nucleus. An increase in p21- and apoptotic-positive cells was also observed in
      lung tumors of mice exposed to p53-modulating agents. These results support a
      chemopreventive role of p53-modulating agents in tobacco carcinogen-induced lung
      adenocarcinoma formation.

PMID- 24027428
TI  - RNF115/BCA2 E3 ubiquitin ligase promotes breast cancer cell proliferation through
      targeting p21Waf1/Cip1 for ubiquitin-mediated degradation.
AB  - The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast
      cancer-associated gene 2 (BCA2), has previously been reported to be overexpressed
      in estrogen receptor alpha (ERalpha)-positive breast tumors and to promote breast
      cell proliferation; however, its mechanism is unknown. In this study, we
      demonstrated that silencing of BCA2 by small interfering RNAs (siRNAs) in two
      ERalpha-positive breast cancer cell lines, MCF-7 and T47D, decreases cell
      proliferation and increases the protein levels of the cyclin-dependent kinase
      inhibitor p21Waf/Cip1. The protein stability of p21 was negatively regulated by
      BCA2. BCA2 directly interacts with p21 and promotes p21 ubiquitination and
      proteasomal degradation. Knockdown of p21 partially rescues the cell growth
      arrest induced by the BCA2 siRNA. These results suggest that BCA2 promotes
      ERalpha-positive breast cancer cell proliferation at least partially through
      downregulating the expression of p21.

PMID- 24027429
TI  - Tpl2 inhibitors thwart endothelial cell function in angiogenesis and peritoneal
      dissemination.
AB  - Angiogenesis is critical in the development of cancer, which involves several
      angiogenic factors in its peritoneal dissemination. The role of protein tumor
      progression locus 2 (Tpl2) in angiogenic factor-related endothelial cell
      angiogenesis is still unclear. To understand the precise mechanism(s) of Tpl2
      inhibition in endothelial cells, this study investigated the role of Tpl2 in
      mediating angiogenic signals using in vitro, in vivo, and ex vivo models. Results
      showed that inhibition of Tpl2 inhibitor significantly reduced peritoneal
      dissemination in a mouse model by positron emission tomography/computed
      tomography imaging. Simultaneously, inhibiting Tpl2 blocked angiogenesis in tumor
      nodules and prevented angiogenic factor-induced proliferating cell nuclear
      antigen (PCNA) in endothelial cells. Vascular endothelial growth factor (VEGF) or
      chemokine (C-X-C motif) ligand 1 (CXCL1) increased Tpl2 kinase activity and
      phosphorylation in a dose- and time-dependent manner. Furthermore, Tpl2
      inhibition or ablation by siRNA prevented the angiogenic signal-induced tube
      formation in Matrigel plug assay or aortic ring assay. Inhibiting Tpl2 also
      prevented the angiogenic factor-induced chemotactic motility and migration of
      endothelial cells. Tpl2 inhibition by CXCL1 or epidermal growth factor in
      endothelial cells was associated with inactivation of CCAAT/enhancer binding
      protein beta, nuclear factor kappa light-chain enhancer of activated B cells, and
      activating protein 1 and suppression of VEGF expression. Thus, Tpl2 inhibitors
      thwart Tpl2-regulated VEGF by inactivating transcription factors involved in
      angiogenic factor-triggered endothelial cell angiogenesis. These results suggest
      that the therapeutic inhibition of Tpl2 may extend beyond cancer and include the
      treatment of other diseases involving pathologic angiogenesis.

PMID- 24027430
TI  - Stress-induced isoforms of MDM2 and MDM4 correlate with high-grade disease and an
      altered splicing network in pediatric rhabdomyosarcoma.
AB  - Pediatric rhabdomyosarcoma (RMS) is a morphologically and genetically
      heterogeneous malignancy commonly classified into three histologic subtypes,
      namely, alveolar, embryonal, and anaplastic. An issue that continues to challenge
      effective RMS patient prognosis is the dearth of molecular markers predictive of
      disease stage irrespective of tumor subtype. Our study involving a panel of 70
      RMS tumors has identified specific alternative splice variants of the oncogenes
      Murine Double Minute 2 (MDM2) and MDM4 as potential biomarkers for RMS. Our
      results have demonstrated the strong association of genotoxic-stress inducible
      splice forms MDM2-ALT1 (91.6% Intergroup Rhabdomyosarcoma Study Group stage 4
      tumors) and MDM4-ALT2 (90.9% MDM4-ALT2-positive T2 stage tumors) with high-risk
      metastatic RMS. Moreover, MDM2-ALT1-positive metastatic tumors belonged to both
      the alveolar (50%) and embryonal (41.6%) subtypes, making this the first known
      molecular marker for high-grade metastatic disease across the most common RMS
      subtypes. Furthermore, our results show that MDM2-ALT1 expression can function by
      directly contribute to metastatic behavior and promote the invasion of RMS cells
      through a matrigel-coated membrane. Additionally, expression of both MDM2-ALT1
      and MDM4-ALT2 increased anchorage-independent cell-growth in soft agar assays.
      Intriguingly, we observed a unique coordination in the splicing of MDM2-ALT1 and
      MDM4-ALT2 in approximately 24% of tumor samples in a manner similar to genotoxic
      stress response in cell lines. To further explore splicing network alterations
      with possible relevance to RMS disease, we used an exon microarray approach to
      examine stress-inducible splicing in an RMS cell line (Rh30) and observed
      striking parallels between stress-responsive alternative splicing and
      constitutive splicing in RMS tumors.

PMID- 24027431
TI  - TBK1 regulates prostate cancer dormancy through mTOR inhibition.
AB  - The mechanisms that regulate hematopoietic stem cell (HSC) dormancy and self
      renewal are well established and are largely dependent on signals emanating from
      the HSC niche. Recently, we found that prostate cancer (PCa) cells target the HSC
      niche in mouse bone marrow (BM) during metastasis. Little is known, however, as
      to how the HSC niche may regulate dormancy in cancer cells. In this study, we
      investigated the effects of TANK binding kinase 1 (TBK1) on PCa dormancy in the
      BM niche. We found that binding with niche osteoblasts induces the expression of
      TBK1 in PCa cells PC3 and C4-2B. Interestingly, TBK1 interacts with mammalian
      target of rapamycin (mTOR) and inhibits its function. Rapamycin, an mTOR
      inhibitor, induces cell cycle arrest of PCa cells and enhances chemotherapeutic
      resistance of PCa cells. As a result, the knockdown of TBK1 decreases PCa stem
      like cells and drug resistance in vitro and in vivo. Taken together, these
      results strongly indicate that TBK1 plays an important role in the dormancy and
      drug resistance of PCa.

PMID- 24027432
TI  - COP1 and GSK3beta cooperate to promote c-Jun degradation and inhibit breast
      cancer cell tumorigenesis.
AB  - High abundance of c-Jun is detected in invasive breast cancer cells and
      aggressive breast tumor malignancies. Here, we demonstrate that a major cause of
      high c-Jun abundance in invasive breast cancer cells is prolonged c-Jun protein
      stability owing to poor poly-ubiquitination of c-Jun. Among the known c-Jun
      targeting E3 ligases, we identified constitutive photomorphogenesis protein 1
      (COP1) as an E3 ligase responsible for c-Jun degradation in less invasive breast
      cancer cells because depletion of COP1 reduced c-Jun poly-ubiquitination leading
      to the stabilization of c-Jun protein. In a panel of breast cancer cell lines, we
      observed an inverse association between the levels of COP1 and c-Jun. However,
      overexpressing COP1 alone was unable to decrease c-Jun level in invasive breast
      cancer cells, indicating that efficient c-Jun protein degradation necessitates an
      additional event. Indeed, we found that glycogen synthase kinase 3 (GSK3)
      inhibitors elevated c-Jun abundance in less invasive breast cancer cells and that
      GSK3beta nonphosphorylable c-Jun-T239A mutant displayed greater protein stability
      and poorer poly-ubiquitination compared to the wild-type c-Jun. The ability of
      simultaneously enforced expression of COP1 and constitutively active GSK3beta to
      decrease c-Jun abundance in invasive breast cancer cells allowed us to conclude
      that c-Jun is negatively regulated through the coordinated action of COP1 and
      GSK3beta. Importantly, co-expressing COP1 and active GSK3beta blocked in vitro
      cell growth/migration and in vivo metastasis of invasive breast cancer cells.
      Gene expression profiling of breast tumor specimens further revealed that higher
      COP1 expression correlated with better recurrence-free survival. Our study
      supports the notion that COP1 is a suppressor of breast cancer progression.

PMID- 24027433
TI  - MicroRNA-130b promotes tumor development and is associated with poor prognosis in
      colorectal cancer.
AB  - MicroRNA-130b (miR-130b) is involved in several biologic processes; its role in
      colorectal tumorigenesis has not been addressed so far. Herein, we demonstrate
      that miR-130b up-regulation exhibits clinical relevance as it is linked to
      advanced colorectal cancers (CRCs), poor patients' prognosis, and molecular
      features of enhanced epithelial-mesenchymal transition (EMT) and angiogenesis.
      miR-130b high-expressing cells develop large, dedifferentiated, and vascularized
      tumors in mouse xenografts, features that are reverted by intratumor injection of
      a specific antisense RNA. In contrast, injection of the corresponding mimic in
      mouse xenografts from miR-130b low-expressing cells increases tumor growth and
      angiogenic potential while reduces the epithelial hallmarks. These biologic
      effects are reproduced in human CRC cell lines. We identify peroxisome
      proliferator-activated receptor gamma (PPARgamma) as an miR-130b direct target in
      CRC in vitro and in vivo. Notably, the effects of PPARgamma gain- and loss-of
      function phenocopy those due to miR-130b down-regulation or up-regulation,
      respectively, underscoring their biologic relevance. Furthermore, we provide
      mechanistic evidences that most of the miR-130b-dependent effects are due to
      PPARgamma suppression that in turn deregulates PTEN, E-cadherin, Snail, and
      vascular endothelial growth factor, key mediators of cell proliferation, EMT, and
      angiogenesis. Since higher levels of miR-130b are found in advanced tumor stages
      (III-IV), we propose a novel role of the miR-130b-PPARgamma axis in fostering the
      progression toward more invasive CRCs. Detection of onco-miR-130b and its
      association with PPARgamma may be useful as a prognostic biomarker. Its targeting
      in vivo should be evaluated as a novel effective therapeutic tool against CRC.

PMID- 24027434
TI  - Tumor microenvironmental signaling elicits epithelial-mesenchymal plasticity
      through cooperation with transforming genetic events.
AB  - Epithelial-to-mesenchymal transition (EMT) facilitates the escape of epithelial
      cancer cells from the primary tumor site, which is a key event early in
      metastasis. Here, we explore how extrinsic, tumor microenvironmental cytokines
      cooperate with intrinsic, genetic changes to promote EMT in human mammary
      epithelial cells (HMECs). Viral transduction of transforming genetic events into
      HMECs routinely generated two distinct cell populations. One population retained
      epithelial characteristics, while an emergent population spontaneously acquired a
      mesenchymal morphology and properties associated with cancer stem cells (CSCs).
      Interestingly, the spontaneous mesenchymal/CSCs were unable to differentiate and
      lacked epithelial-mesenchymal plasticity. In contrast, exposure of the
      transformed HMECs retaining epithelial characteristics to exogenous transforming
      growth factor-beta (TGF-beta) generated a mesenchymal/CSC population with
      remarkable plasticity. The TGF-beta-induced mesenchymal/CSC population was
      dependent on the continued presence of TGF-beta. Removal of TGF-beta or
      pharmacologic or genetic inhibition of TGF-beta/SMAD signaling led to the
      reversion of mesenchymal/CSC to epithelial/non-CSC. Our results demonstrate that
      targeting exogenous cytokine signaling disrupts epithelial-mesenchymal plasticity
      and may be an effective strategy to inhibit the emergence of circulating tumor
      cells. The model of epithelial-mesenchymal plasticity we describe here can be
      used to identify novel tumor microenvironmental factors and downstream signaling
      that cooperate with intrinsic genetic changes to drive metastasis. Understanding
      the interaction between extrinsic and intrinsic factors that regulate epithelial
      mesenchymal plasticity will allow the development of new therapies that target
      tumor microenvironmental signals to reduce metastasis.

PMID- 24027436
TI  - The Effect of Budgetary Restrictions on Breast Cancer Diagnostic Decisions.
AB  - We develop a finite-horizon discrete-time constrained Markov decision process
      (MDP) to model diagnostic decisions after mammography where we maximize the total
      expected quality-adjusted life years (QALYs) of a patient under resource
      constraints. We use clinical data to estimate the parameters of the MDP model and
      solve it as a mixed-integer program. By repeating optimization for a sequence of
      budget levels, we calculate incremental cost-effectiveness ratios attributable to
      consecutive levels of funding and compare actual clinical practice with optimal
      decisions. We prove that the optimal value function is concave in the allocated
      budget. Comparing to actual clinical practice, using optimal thresholds for
      decision making may result in approximately 22% cost savings without sacrificing
      QALYs. Our analysis indicates short-term follow-ups are the immediate target for
      elimination when budget becomes a concern. Policy change is more drastic in the
      older age group with the increasing budget, yet the gains in total expected QALYs
      related to larger budgets are predominantly seen in younger women along with
      modest gains for older women.

PMID- 24027435
TI  - Human T cell leukemia virus type I tax-induced IkappaB-zeta modulates tax
      dependent and tax-independent gene expression in T cells.
AB  - Human T cell leukemia virus type I (HTLV-I) is the etiologic agent of adult T
      cell leukemia (ATL) and various inflammatory disorders including HTLV-I
      associated myelopathy/tropical spastic paraparesis. HTLV-I oncoprotein Tax is
      known to cause permanent activation of many cellular transcription factors
      including nuclear factor-kappaB (NF-kappaB), cyclic adenosine 3',5'-monophosphate
      response element-binding protein, and activator protein 1 (AP-1). Here, we show
      that NF-kappaB-binding cofactor inhibitor of NF-kappaB-zeta (IkappaB-zeta) is
      constitutively expressed in HTLV-I-infected T cell lines and ATL cells, and Tax
      transactivates the IkappaB-zeta gene, mainly through NF-kappaB. Microarray
      analysis of IkappaB-zeta-expressing uninfected T cells demonstrated that IkappaB
      zeta induced the expression of NF-kappaB. and interferon-regulatory genes such as
      B cell CLL/lymphoma 3 (Bcl3), guanylate-binding protein 1, and signal transducer
      and activator of transcription 1. The transcriptional activation domain, nuclear
      localization signal, and NF-kappaB-binding domain of IkappaB-zeta were required
      for Bcl3 induction, and IkappaB-zeta synergistically enhanced Tax-induced Bcl3
      transactivation in an NF-kappaB-dependent manner. Interestingly, IkappaB-zeta
      inhibited Tax-induced NF-kappaB, AP-1 activation, and HTLV-I transcription.
      Furthermore, IkappaB-zeta interacted with Tax in vitro and this interaction was
      also observed in an HTLV-I-transformed T cell line. These results suggest that
      IkappaB-zeta modulates Tax-dependent and Tax-independent gene transcription in T
      cells. The function of IkappaB-zeta may be of significance in ATL genesis and
      pathogenesis of HTLV-I-associated diseases.

PMID- 24027437
TI  - Posture Development in Infants at Heightened vs. Low Risk for Autism Spectrum
      Disorders.
AB  - Evidence suggests that children and adults diagnosed with autism spectrum
      disorders (ASD) exhibit difficulties with postural control. Retrospective video
      studies of infants later diagnosed with ASD indicate that infants who eventually
      receive an ASD diagnosis exhibit delays in postural development. This study
      investigates early posture development prospectively and longitudinally in 22
      infants at heightened biological risk for ASD (HR) and 18 infants with no such
      risk (Low Risk; LR). Four HR infants received an autism diagnosis (AD infants) at
      36 months. Infants were videotaped at home at 6, 9, 12, and 14 months during
      everyday activities and play. All infant postures were coded and classified as to
      whether or not they were infant-initiated. Relative to LR infants, HR infants
      were slower to develop skill in sitting and standing postures. AD infants
      exhibited substantial delays in the emergence of more advanced postures and
      initiated fewer posture changes. Because posture advances create opportunities
      for infants to interact with objects and people in new and progressively more
      sophisticated ways, postural delays may have cascading effects on opportunities
      for infant exploration and learning. These effects may be greater for infants
      with ASD, for whom posture delays are more significant.

PMID- 24027438
TI  - Absorbing a Little Water: The Structural, Thermodynamic, and Kinetic Relationship
      between Pyrogallol and Its Tetarto-Hydrate.
AB  - The anhydrate and the stoichiometric tetarto-hydrate of pyrogallol (0.25 mol
      water per mol pyrogallol) are both storage stable at ambient conditions, provided
      that they are phase pure, with the system being at equilibrium at aw (water
      activity) = 0.15 at 25  degrees C. Structures have been derived from single
      crystal and powder X-ray diffraction data for the anhydrate and hydrate,
      respectively. It is notable that the tetarto-hydrate forms a tetragonal structure
      with water in channels, a framework that although stabilized by water, is found
      as a higher energy structure on a computationally generated crystal energy
      landscape, which has the anhydrate crystal structure as the most stable form.
      Thus, a combination of slurry experiments, X-ray diffraction, spectroscopy,
      moisture (de)sorption, and thermo-analytical methods with the computationally
      generated crystal energy landscape and lattice energy calculations provides a
      consistent picture of the finely balanced hydration behavior of pyrogallol. In
      addition, two monotropically related dimethyl sulfoxide monosolvates were found
      in the accompanying solid form screen.

PMID- 24027440
TI  - On generalized Carleson operators of periodic wavelet packet expansions.
AB  - Three new theorems based on the generalized Carleson operators for the periodic
      Walsh-type wavelet packets have been established. An application of these
      theorems as convergence a.e. for the periodic Walsh-type wavelet packet expansion
      of block function with the help of summation by arithmetic means has been
      studied. 

PMID- 24027439
TI  - Antimelanoma and antityrosinase from Alpinia galangal constituents.
AB  - Two compounds, 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (BHPHTO) and
      bisdemethoxycurcumin (BDMC) they have been isolated from the rhizomes of Alpinia
      galangal, and the structures of both pure constituents were determined using
      spectroscopic analyses. The study examined the bioeffectivenesses of the two
      compounds on the human melanoma A2058 and showed that significantly inhibited the
      proliferation of melanoma cells in the cell viability assay. This research was
      also taken on the tests to B16-F10 cell line and showed minor inhibitory
      consequences of cellular tyrosinase activities and melanin contents. Our results
      revealed the anticancer effects of A. galangal compounds, and therefore, the
      target compounds could be potentially applied in the therapeutic application and
      the food industry. 

PMID- 24027441
TI  - Impacts of intensified agriculture developments on marsh wetlands.
AB  - A spatiotemporal analysis on the changes in the marsh landscape in the Honghe
      National Nature Reserve, a Ramsar reserve, and the surrounding farms in the core
      area of the Sanjiang Plain during the past 30 years was conducted by integrating
      field survey work with remote sensing techniques. The results indicated that
      intensified agricultural development had transformed a unique natural marsh
      landscape into an agricultural landscape during the past 30 years. Ninety percent
      of the natural marsh wetlands have been lost, and the areas of the other natural
      landscapes have decreased very rapidly. Most dry farmland had been replaced by
      paddy fields during the progressive change of the natural landscape to a farm
      landscape. Attempts of current Chinese institutions in preserving natural
      wetlands have achieved limited success. Few marsh wetlands have remained healthy,
      even after the establishment of the nature reserve. Their ecological qualities
      have been declining in response to the increasing threats to the remaining
      wetland habitats. Irrigation projects play a key role in such threats. Therefore,
      the sustainability of the natural wetland ecosystems is being threatened by
      increased regional agricultural development which reduced the number of wetland
      ecotypes and damaged the ecological quality. 

PMID- 24027442
TI  - Annotation of differentially expressed genes in the somatic embryogenesis of musa
      and their location in the banana genome.
AB  - Analysis of cDNA-AFLP was used to study the genes expressed in zygotic and
      somatic embryogenesis of Musa acuminata Colla ssp. malaccensis, and a comparison
      was made between their differential transcribed fragments (TDFs) and the
      sequenced genome of the double haploid- (DH-) Pahang of the malaccensis
      subspecies that is available in the network. A total of 253 transcript-derived
      fragments (TDFs) were detected with apparent size of 100-4000 bp using 5 pairs of
      AFLP primers, of which 21 were differentially expressed during the different
      stages of banana embryogenesis; 15 of the sequences have matched DH-Pahang
      chromosomes, with 7 of them being homologous to gene sequences encoding either
      known or putative protein domains of higher plants. Four TDF sequences were
      located in all Musa chromosomes, while the rest were located in one or two
      chromosomes. Their putative individual function is briefly reviewed based on
      published information, and the potential roles of these genes in embryo
      development are discussed. Thus the availability of the genome of Musa and the
      information of TDFs sequences presented here opens new possibilities for an in
      depth study of the molecular and biochemical research of zygotic and somatic
      embryogenesis of Musa. 

PMID- 24027443
TI  - Effect of CO2 flow rate on the Pinang frond-based activated carbon for methylene
      blue removal.
AB  - Activated carbons are regularly used the treatment of dye wastewater. They can be
      produced from various organics materials having high level of carbon content. In
      this study, a novel Pinang frond activated carbon (PFAC) was produced at various
      CO2 flow rates in the range of 150-600 mL/min at activation temperature of 800
      degrees C for 3 hours. The optimum PFAC sample is found on CO2 flow rate of 300
      mL/min which gives the highest BET surface area and pore volume of 958 m2/g and
      0.5469 mL/g, respectively. This sample shows well-developed pore structure with
      high fixed carbon content of 79.74%. The removal of methylene blue (MB) by 95.8%
      for initial MB concentration of 50 mg/L and 72.6% for 500 mg/L is achieved via
      this sample. The PFAC is thus identified to be a suitable adsorbent for removing
      MB from aqueous solution.

PMID- 24027444
TI  - Thermal stability analysis under embankment with asphalt pavement and cement
      pavement in permafrost regions.
AB  - The permafrost degradation is the fundamental cause generating embankment
      diseases and pavement diseases in permafrost region while the permafrost
      degradation is related with temperature. Based on the field monitoring results of
      ground temperature along G214 Highway in high temperature permafrost regions,
      both the ground temperatures in superficial layer and the annual average
      temperatures under the embankment were discussed, respectively, for concrete
      pavements and asphalt pavements. The maximum depth of temperature field under the
      embankment for concrete pavements and asphalt pavements was also studied by using
      the finite element method. The results of numerical analysis indicate that there
      were remarkable seasonal differences of the ground temperatures in superficial
      layer between asphalt pavement and concrete pavement. The maximum influencing
      depth of temperature field under the permafrost embankment for every pavement was
      under the depth of 8 m. The thawed cores under both embankments have close
      relation with the maximum thawed depth, the embankment height, and the service
      time. The effective measurements will be proposed to keep the thermal stabilities
      of highway embankment by the results. 

PMID- 24027445
TI  - The influence of storage temperature on the antibiotic release of vancomycin
      loaded polymethylmethacrylate.
AB  - Periprosthetic joint infection is devastating and increases medical expenditure
      and socioeconomic burden. Antibiotic-loaded cement spacer is useful in the
      interim period before the reimplantation surgery. Prefabricated antibiotic-loaded
      cement spacers can decrease operation time but have been limitedly used
      clinically. In the literature, there is no clear recommendation on the storage
      temperature for the prefabricated cement spacers. We used an in vitro model to
      analyze whether the storage temperature at 25 degrees C, 4 degrees C, or -20
      degrees C for 2 weeks or 3 months could affect the release of vancomycin from the
      cement. We found that the storage temperature and time had no significant effects
      on the pattern and amount of vancomycin release. The patterns of vancomycin
      release from the cement stored at different temperatures were similar with an
      abrupt release in the first 3 days and steadily declined in the following period.
      This study provides a preliminary result to justify the storage of fabricating
      antibiotic-loaded cement spacer sterilely packed at room temperature. Further
      studies to examine the effects of storage temperature on the mechanical strength
      and the release pattern of other antibiotics should be done to provide more
      evidence to support the clinical use of prefabricated ready-to-use antibiotic
      loaded cement spacer. 

PMID- 24027446
TI  - Robust H(infinity) control for spacecraft rendezvous with a noncooperative
      target.
AB  - The robust H(infinity) control for spacecraft rendezvous with a noncooperative
      target is addressed in this paper. The relative motion of chaser and
      noncooperative target is firstly modeled as the uncertain system, which contains
      uncertain orbit parameter and mass. Then the H(infinity) performance and finite
      time performance are proposed, and a robust H(infinity) controller is developed
      to drive the chaser to rendezvous with the non-cooperative target in the presence
      of control input saturation, measurement error, and thrust error. The linear
      matrix inequality technology is used to derive the sufficient condition of the
      proposed controller. An illustrative example is finally provided to demonstrate
      the effectiveness of the controller.

PMID- 24027447
TI  - Updating categorical soil maps using limited survey data by Bayesian Markov chain
      cosimulation.
AB  - Updating categorical soil maps is necessary for providing current, higher-quality
      soil data to agricultural and environmental management but may not require a
      costly thorough field survey because latest legacy maps may only need limited
      corrections. This study suggests a Markov chain random field (MCRF) sequential
      cosimulation (Co-MCSS) method for updating categorical soil maps using limited
      survey data provided that qualified legacy maps are available. A case study using
      synthetic data demonstrates that Co-MCSS can appreciably improve simulation
      accuracy of soil types with both contributions from a legacy map and limited
      sample data. The method indicates the following characteristics: (1) if a soil
      type indicates no change in an update survey or it has been reclassified into
      another type that similarly evinces no change, it will be simply reproduced in
      the updated map; (2) if a soil type has changes in some places, it will be
      simulated with uncertainty quantified by occurrence probability maps; (3) if a
      soil type has no change in an area but evinces changes in other distant areas, it
      still can be captured in the area with unobvious uncertainty. We concluded that
      Co-MCSS might be a practical method for updating categorical soil maps with
      limited survey data. 

PMID- 24027448
TI  - Oscillation of a class of fractional differential equations with damping term.
AB  - We investigate the oscillation of a class of fractional differential equations
      with damping term. Based on a certain variable transformation, the fractional
      differential equations are converted into another differential equations of
      integer order with respect to the new variable. Then, using Riccati
      transformation, inequality, and integration average technique, some new
      oscillatory criteria for the equations are established. As for applications,
      oscillation for two certain fractional differential equations with damping term
      is investigated by the use of the presented results. 

PMID- 24027449
TI  - Co(II) and Cd(II) complexes derived from heterocyclic Schiff-Bases: synthesis,
      structural characterisation, and biological activity.
AB  - New monomeric cobalt and cadmium complexes with Schiff-bases, namely, N'-[(E)-(3
      hydroxy-4-methoxyphenyl)methylidene]furan-2-carbohydrazide (L1) and N'-[(E)-(3
      hydroxy-4-methoxyphenyl)methylidene]thiophene-2-carbohydrazide (L2) are reported.
      Schiff-base ligands L1 and L2 were derived from condensation of 3-hydroxy-4
      methoxybenzaldehyde (iso-vanillin) with furan-2-carboxylic acid hydrazide and
      thiophene-2-carboxylic acid hydrazide, respectively. Complexes of the general
      formula [M(L)2]Cl2 (where M = Co(II) or Cd(II), L = L1 or L2) have been obtained
      from the reaction of the corresponding metal chloride with the ligands. The
      ligands and their metal complexes were characterised by spectroscopic methods
      (FTIR, UV-Vis, 1H, and 13C NMR spectra), elemental analysis, metal content,
      magnetic measurement, and conductance. These studies revealed the formation of
      four-coordinate complexes in which the geometry about metal ion is tetrahedral.
      Biological activity of the ligands and their metal complexes against gram
      positive bacterial strain Bacillus (G+) and gram negative bacteria Pseudomonas (G
      ) revealed that the metal complexes become less resistive to the microbial
      activities as compared to the free ligands.

PMID- 24027451
TI  - Size effect and material property effect of the impactor on the damage modes of
      the single-layer Kiewitt-8 reticulated dome.
AB  - The dynamic response of large space structures under accidental impact has been
      the subject of intense research since the occurrence of the 9/11 incident. In the
      present paper, using the 3D ANSYS/LS-DYNA, size effect and material property
      effect of the impactor on the damage modes of the single-layer Kiewitt-8
      reticulated dome were investigated, respectively, where the impactor was the
      cylinder and the impact direction was vertical. Firstly, analytical results with
      the rigid impactor indicated that the impactor size can change the damage mode of
      the reticulated dome. It was found that the probability happening to the global
      collapse has an obvious rise with the size increase of the impactor. Furthermore,
      the deformable impactor was considered to figure out the difference with the
      rigid impactor; the comparisons indicated that the deformable impactor, which has
      the same mass and the same striking velocity with the rigid impactor, can
      contribute to the occurrence of the global collapse at a certain initial striking
      condition. 

PMID- 24027450
TI  - Microscale obstacle resolving air quality model evaluation with the Michelstadt
      case.
AB  - Modelling pollutant dispersion in cities is challenging for air quality models as
      the urban obstacles have an important effect on the flow field and thus the
      dispersion. Computational Fluid Dynamics (CFD) models with an additional scalar
      dispersion transport equation are a possible way to resolve the flowfield in the
      urban canopy and model dispersion taking into consideration the effect of the
      buildings explicitly. These models need detailed evaluation with the method of
      verification and validation to gain confidence in their reliability and use them
      as a regulatory purpose tool in complex urban geometries. This paper shows the
      performance of an open source general purpose CFD code, OpenFOAM for a complex
      urban geometry, Michelstadt, which has both flow field and dispersion measurement
      data. Continuous release dispersion results are discussed to show the strengths
      and weaknesses of the modelling approach, focusing on the value of the turbulent
      Schmidt number, which was found to give best statistical metric results with a
      value of 0.7. 

PMID- 24027453
TI  - The gothic arch: a reliable measurement for developmental dysplasia of the hip.
AB  - BACKGROUND: The "Gothic Arch" is a radio-graphic finding on AP pelvis x-rays
      postulated to be predictive of hip osteoarthritis. PURPOSE: The purpose of this
      study was to determine the reliability of measurement of the Gothic Arch in
      patients with no known hip pathology and patients with unilateral developmental
      dysplasia of the hip (DDH). PATIENTS AND METHODS: After obtaining IRB approval,
      nine skeletally mature patients (18 hips) with no known hip pathology were
      selected to serve as the control group. The AP pelvis x-rays at skeletal maturity
      of eight patients (16 hips) with unilateral DDH treated with closed reduction and
      casting comprised the comparison group. A digitizing program was designed to
      measure the Gothic Arch based on landmarks identified by the user. Two pediatric
      orthopaedic surgeons and two orthopaedic residents completed the program on two
      separate occasions. Intra-and interobserver reliability were determined using
      intraclass cor-relation coefficients (ICC) for continuous variables. RESULTS:
      Both the unilateral DDH group and the control group demonstrated excellent inter-
      and intraobserver reliability (ICC >0.70) for base, height, area, and orientation
      of the Gothic Arch, but poor reliability (ICC <0.40) for medial and lateral
      sharpness. CONCLUSION: The Gothic Arch can be reliably measured on AP pelvis x
      rays of patients with normal and dysplastic hips. LEVEL OF EVIDENCE: III,
      Diagnostic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 24027454
TI  - Healing results of periprosthetic distal femur fractures treated with far
      cortical locking technology: a preliminary retrospective study.
AB  - INTRODUCTION: Periprosthetic distal femur fractures are severe injuries occurring
      in the often osteoporotic bone of the elderly. Far cortical locking (FCL) screws,
      which have been shown to promote increased callus formation in animal models,
      have recently become available for clinical use. The purpose of this study is to
      report preliminary healing and complication rates of periprosthetic distal femur
      fractures treated with FCL constructs. MATERIALS AND METHODS: A retrospective
      review of 20 patients who underwent open reduction and internal fixation of
      periprosthetic distal femur fractures using FCL constructs was performed. Healing
      was assessed radiographically and clinically at 6, 12 and 24 weeks post
      operatively. Construct failure was defined as any hardware breakage or bone
      implant dissociation leading to loss of reduction. RESULTS: Complete data through
      the 24 week study period was available for 18/20 patients. Bridging callus was
      identified in 16/18 patients by the 24 week follow up for a healing rate of
      88.9%. In patients that healed, the average time to medial bridging callus
      formation was 10.7 +/- 6.7 weeks, 11.0 +/- 6.6 weeks for anterior fracture line
      and 13.4 +/- 7.5 weeks for the posterior fracture line. both patients that failed
      to heal underwent revision surgery. DISCUSSION: The initial results of this study
      are comparable to results reported for distal femur periprosthetic fractures
      treated with locking plate fixation without FCL screws, although it was difficult
      to compare time to healing between previously published studies. It is the
      impression of the authors that callus appears earlier and is more robust and
      uniform between the three cortices in FCL cases compared to their previous
      experiences with traditional locking plate periprosthetic distal femur fractures.
      This work suggests that FCL screws may be superior to traditional locking
      constructs but further studies are needed to directly compare the two methods.

PMID- 24027455
TI  - Outcomes following operative treatment of open fractures of the distal radius: a
      case control study.
AB  - PURPOSE: To report radiographic, clinical, and patient-based functional outcomes
      following contemporary operative treatment of patients who sustained an open
      distal radius fracture and compare them to a similar group of patients treated
      operatively for closed distal radius fractures. METHODS: Over five years, 601
      patients with a distal radius fracture presented to our academic medical center,
      including one Level 1 trauma hospital, and were prospectively enrolled in an
      upper extremity trauma database. Patients with open distal radius fractures
      underwent irrigation, debridement, and operative fixation within 24 hours of
      presentation. Closed distal radius fractures requiring operative fixation were
      treated electively. Retrospective review of the database identified eighteen open
      fractures of the distal radius (11 type I, 6 type II, 1 type IIIa). The open
      fracture patients were individually matched with eighteen closed distal radius
      fracture patients who underwent surgical fixation based on age, sex, injury to
      dominant extremity, fracture pattern, and method of fracture fixation. Clinical,
      radiographic, patient- based functional outcomes, and complications were recorded
      at routine postoperative intervals. RESULTS: Follow-up was greater than 77% in
      both groups at all time points. The open and closed groups were similar in
      regards to age, gender, BMI, race, tobacco use, income, employment status, hand
      dominance, injury to dominant extremity, mechanism of injury, fracture
      classification, method of fracture fixation, and presence of concomitant injury.
      Postoperative complications and reoperation rates were similar between the open
      and closed groups. Union rates and radiographic alignment one year
      postoperatively were similar between the open and closed fracture groups. At
      final follow-up, range of motion parameters, grip strengths, DASH indices, and
      subjective pain scores were similar between both groups. DISCUSSION: Open distal
      radius fractures treated with early debridement and fixation achieved similar
      outcomes to surgically treated closed fractures of the distal radius when
      followed for a year or more postoperatively.

PMID- 24027456
TI  - The use of a multiplanar, multi-axis external fixator to achieve knee arthrodesis
      in a worst case scenario: a case series.
AB  - BACKGROUND: One of the most catastrophic outcomes following total knee
      arthroplasty (TKA) is a chronic periprosthetic infection with concomitant failure
      of the knee extensor mechanism. This study retrospectively reviewed the clinical
      records of 7 patients who were treated with a 6 axis circular external fixation
      frame (Taylor Spatial Frame (TSF)) for this condition. Fusion was achieved in 5
      of 7 patients (71%) at an average of 8.4 months after surgery. Complications
      occurred in the treatment of 5 of 7 patients (71%). Infection was controlled in
      all cases. The TSF presents another valuable tool, which the orthopaedic surgeon
      should consider when treating these difficult cases. PURPOSE: To evaluate the use
      of the Taylor Spatial Frame (TSF) to achieve knee arthrodesis in patients with
      chronically infected total knee arthroplasties (TKAs) with concomitant failure of
      the knee extensor mechanism. METHODS: We retrospectively evaluated the clinical
      records of 7 patients who were referred to our tertiary care orthopaedic medical
      center with multiple failed knee arthroplasties, chronic draining infection and
      complete loss of the extensor mechanism. All patients were treated with a similar
      protocol including, debridement and bony stabilization with an adjustable, 6 axis
      circular external fixation frame (TSF). Hospital charts were reviewed for
      sociodemographic information, surgical details, hospital course and
      complications. Radiographs were reviewed for healing and alignment. Follow up
      included clinical examination and radiographs. RESULTS: The mean age of the
      patients was 70.9 years (range, 59 - 83 years) at the time of application of the
      TSF. There were 3 men and 4 women. The average time between TKA and diagnosis of
      infection was 30.7 months (range, 2.6 - 67.0 months). The 7 patients had
      undergone an average of 3.3 prior surgical procedures (range, 2-4 procedures) on
      the ipsilateral extremity. Fusion was achieved in 5 of 7 patients (71%) at an
      average of 8.4 months after surgery (range, 6 - 10.5 months). Complications
      occurred in the treatment of 5 of 7 patients (71%) and included infection at the
      site of the pin tracks (5 patients), antibiotic- induced acute renal failure (1
      patient), wound breakdown requiring flap closure (1 patient), and femur fracture
      secondary to a fall after placement of the antibiotic spacer but before
      application of the TSF (1 patient). The 2 patients in whom failure of fusion
      occurred returned to ambulation with an assistive device. Infection was
      controlled in all cases. CONCLUSION: Fusion and complication rates in this cohort
      are comparable to those reported in previous studies using other techniques to
      achieve external fixation. The TSF is a versatile external fixator that offers
      another tool, which the orthopaedic surgeon should consider when treating these
      difficult cases.

PMID- 24027457
TI  - Evaluation of a novel silicate substituted hydroxyapatite bone graft substitute
      in a rabbit posterolateral fusion model.
AB  - STUDY DESIGN/SETTING: Randomized, controlled study in a laboratory setting.
      Blinded observations/assessment of study outcomes. OBJECTIVE: The purpose of this
      study is to determine the performance characteristics of a novel silicate
      substituted hydroxyapatite bone graft substitute (BGS), SiCaP EP (Baxter
      Healthcare/ ApaTech, Elstree, UK), in a stand-alone mode, a stand-alone with bone
      marrow aspirate (BMA) mode, and an extender mode with iliac crest autograft
      (ICBG) in a rabbit posterolateral spine fusion model. The investigational BGS is
      compared to a standard iliac crest autograft (ICBG) control. SUMMARY OF
      BACKGROUND DATA: The rabbit posterolateral fusion model is an established
      environment for testing of fusion efficacy. It offers the opportunity to obtain
      radiographic, histological, and biomechanical data on novel bone graft
      substitutes. METHODS: One hundred and twenty rabbits were entered into the study
      with 116 used for analysis. Bilateral posterolateral lumbar intertransverse
      fusions were performed at L5-L6. The lateral two thirds of the transverse
      processes were decorti cated and covered with graft material in the following
      five groups: ICBG, SiCaP EP stand-alone, SiCaP EP with BMA (1:0.5 by volume), and
      SiCaP EP with ICBG (1:3 by volume). Rabbits were necropsied at 4, 8, and 12-week
      time points and fusion rate, quantity, and quality was evaluated based on manual
      palpation, mechanical stiffness testing, pqCT, and histological assessment.
      RESULTS: SiCaP EP, ICBG+SiCaP EP (3:1), and SiCaP EP+BMA (1:0.5) compare
      favorably to iliac crest autologous bone by multiple metrics in this rabbit
      posterolateral fusion model. Fusion efficacy via manual palpation and mechanical
      stiffness testing metrics indicate that all SiCaP EP groups had similar group-to
      group performance, and were not significantly different than the ICBG control at
      each time period evaluated. CONCLUSIONS: In this commonly used rabbit
      posterolateral fusion model, SiCaP EP utilized as a stand-alone, as a stand-alone
      with BMA, and as an autograft (ICBG) extender produces results that are
      clinically and radiographically similar to ICBG.

PMID- 24027458
TI  - Assessment of BioPlex interbody fusion device in a sheep lumbar fusion model.
AB  - OBJECTIVE: The purpose of this study was to evaluate the bioPlex bioresorbable
      interbody device in a sheep lumbar fusion model and compare it to the concorde, a
      standard carbon fiber interbody cage. BACKGROUND: Lumbar interbody fusion devices
      are made from a variety of materials, including titanium alloys, carbon-fiber,
      and PEEK. The BioPlex Continuous Phase Composite (CPC) is a unique bioresorbable
      material comprised of Pro Osteon 500R and 70:30 Poly (L/D, L-lactic acid). The
      BioPlex device is radiolucent, resorbable and due to its bulk nanoporosity of 8%,
      has a more consistent degradation profile as compared to a polymer alone.
      METHODS: A total of twenty five male Suffolk sheep were used in this study;
      nineteen of which were implanted with a bioPlex or concorde device at the L3-L4
      and L5-L6 levels using a modified transforaminal/lateral approach. A discectomy
      was performed and each implant (filled with autologous bone) was placed within
      the disc space. The sheep were sacrificed at 6, 12, 24 months postimplantation.
      Fusion was assessed via motion, radiographic and histological data. RESULTS: The
      BioPlex and Concorde implanted levels had significantly less motion (p<0.05) than
      the normal controls in flexion/extension and lateral bending at 6, 12, and 24
      months. No significant difference in motion was detected between the bioPlex and
      concorde implants. CT fusion scores correlated with the motion analysis in all
      the three cases. CONCLUSION: In comparison to the concorde device, the bioPlex
      implant appears to have equivalent radiographic and biomechanical fusion success.

PMID- 24027459
TI  - 3D model analysis of existing CT syndesmosis measurements.
AB  - INTRODUCTION: Use of Computed Tomography (CT) to evaluate syndesmotic reduction
      following injury has significantly increased in recent years. The aim of this
      study was to compare existing clinical measurements of syndesmotic reduction to
      gold standard measurements of fibular motion obtained from a full 3D model.
      METHODS: Three common clinical measures for assessing syndesmotic congruity on
      axial CT slices were identified in the literature. Each measure was manually
      performed on 170 cadaveric ankle CT scans obtained with variable degrees of
      simulated syndesmotic displacement. Clinical measures were assessed for
      intraobserver and interobserver reliability and compared to objective measures of
      true medial/lateral and anterior/posterior translation and fibular rotation that
      were obtained from a 3D model. Pearson correlation coefficients (PCC) were
      computed to determine which clinical measurements were most accurate for
      describing syndesmotic motion obtained from the 3D model. RESULTS: All three
      clinical measurement techniques demonstrated good to excellent interobserver and
      intraobserver reliability. Medial/lateral displacement of the fibula was best
      correlated with the difference between the anterior and posterior tibiofibular
      joint space measurements described by Elgafy et al (PCC = 0.29 small
      correlation). Anterior/posterior displacement of the fibula was well correlated
      with the anterior/posterior measurement described by Phisitkul et al (PCC = 0.69
      large correlation). Fibular rotation was best correlated with the average of the
      Elgafy anterior and posterior tibiofibular joint space measurements (PCC = 0.33,
      moderate correlation). Proximal/ distal displacement of the lateral malleolus was
      best correlated with the Elgafy posterior tibiofibular joint space measurement
      (PCC = 0.49, moderate correlation). DISCUSSION: While the clinical measurements
      were adequately reproducible, they showed only moderate to small correlations
      with the 3D measurements of movement of the fibula in the longitudinal,
      medial/lateral or rotational directions. The only fibular translation measured by
      the 3D model that was well described by the three clinical measures was fibular
      movement in the anterior/ posterior direction. This work demonstrates a need for
      improved clinical measurements of syndesmotic congruity on axial CT scans to
      serve as surrogates for the true movement of the fibula.

PMID- 24027460
TI  - Tripod Index: diagnostic accuracy in symptomatic flatfoot and cavovarus foot:
      part 2.
AB  - BACKGROUND: The Tripod Index (TI) has been created to allow assessment of complex
      foot deformities. It utilizes tripod relationship between center of the heel,
      medial/lateral borders of the forefoot, and compare it to the center of the talar
      head. This study aimed to verify diagnostic accuracy of the TI in symptomatic
      flatfoot and cavovarus foot. METHODS: Weightbearing radiographs including foot AP
      with a hemispherical marker around the heel, lateral, and hindfoot alignment
      views were obtained on 91 patients (110 feet) presenting with medial foot and
      ankle pain and on 89 patients (90 feet) presenting with lateral foot and ankle
      pain between June 2010 and May 2011. Radiographs were evaluated blindly for the
      TI, AP talonavicular coverage angle, lateral talo-first metatarsal angle,
      calcaneal pitch angle, medial cuneiform-fifth metatarsal height, and coronal
      plane hindfoot alignment. The sensitivity, specificity, likelihood ratios, and
      predictive values were calculated. Clinically diagnosed flatfoot and cavovarus
      foot deformity indicated for surgical reconstruction by one of our foot and ankle
      orthopaedic surgeons was used as the accepted standard for diagnosis. RESULTS: In
      flatfoot, sensitivity of the TI was 100%, comparable with lateral talo-first
      metatarsal angle (100%), and medial cuneiform-fifth metatarsal height (100%).
      Specificity of the TI was 93%, comparable with coronal plane hindfoot alignment
      (98%), but superior to other parameters. Positive likelihood ratio of the TI was
      14.29, which was less than coronal plane hindfoot alignment (47.5), but more than
      other parameters. In cavovarus foot, sensitivity of the TI was 96%, comparable
      with coronal plane hindfoot alignment (100%), but superior to other parameters.
      Specificity of the TI was 95%, comparable with lateral talo-first metatarsal
      angle (94%), but superior to other parameters. Positive likelihood ratio of the
      TI was 19.2, which was more than other parameters. CONCLUSION: The Tripod Index
      showed high accuracy as a quantitative assessment in diagnosis of a symptomatic
      flatfoot and cavovarus foot.

PMID- 24027461
TI  - Severe degeneration of the medial collateral ligament in hallux valgus: a
      histopathologic study in 12 consecutive patients.
AB  - OBJECTIVE: To determine the degree and location of degenerative changes of the
      medial collateral ligament of the first metatarsophalangeal joint, using the
      lateral collateral ligament as a control, in patients undergoing hallux valgus
      correction. MATERIALS AND METHODS: A strip of medial and lateral collateral
      ligaments were biopsied from 12 consecutive patients (age 45 +/- 4.8 years) with
      symptomatic hallux valgus. A blinded analysis of histopathology was performed by
      an experienced pathologist. RESULTS: The medial collateral ligament was
      significantly more degenerated compared to the lateral collateral ligament (x(2)
      = 23.41, DF = 2, p < 0.0001). There was no significant difference in degeneration
      between different parts of each ligament. CONCLUSION: Our study found generalized
      severe degeneration in the medial collateral ligament without proximal-distal
      predilection. This information may have implications in the management of medial
      soft tissue repair in hallux valgus correction. The Authors received no financial
      support for this study.

PMID- 24027462
TI  - Femoral tunnel placement in medial patellofemoral ligament reconstruction.
AB  - INTRODUCTION: Medial Patellofemoral Ligament (MPFL) reconstruction is an accepted
      treatment for recurrent patellofemoral instability when patients have normal
      alignment and deficient proximal medial restraints. There are several reports of
      malpositioned femoral tunnels leading to poor outcomes. The purpose of this study
      was to analyze femoral tunnel placement after MPFL reconstruction and correlate
      this with outcomes. METHODS: We performed a retrospective review of MPFL
      reconstructions done at our institution from 2006-2010. We then evaluated lateral
      radiographs and measured the distance between the radiographic femoral MPFL
      isometric point and the center of the femoral tunnel. We also evaluated post
      operative KOOS scores. RESULTS: The average distance from the femoral tunnel to
      the MPFL isometric point was 13.25 mm. Sixty-four percent of tunnels were placed
      greater than nine millimeters from our isometric point and deemed to be
      malpositioned. There was no statistically significant difference in outcomes
      scores in patients with anatomically placed MPFL tunnels when compared to those
      placed non-anatomically. CONCLUSION: Sixty-four percent of MPFL reconstruction
      femoral tunnels were placed non-anatomically, but this did not correlate with a
      worse outcome. Graft tension, trochlear groove anatomy, patellar height, and
      dynamic restraints all play important roles in outcomes after MPFL
      reconstruction. Even though non-anatomic tunnel placement does not guarantee a
      poor result, we believe an anatomic tunnel placement will give the best chance to
      maximize graft function and outcome.

PMID- 24027463
TI  - Biomechanical evaluation of medial patellofemoral ligament reconstruction.
AB  - BACKGROUND: The medial patellofemoral ligament (MPFL) is the most frequently
      injured soft tissue structure following acute lateral patellar dislocation. MPFL
      reconstruction has become a popular option to restore patellar stability
      following lateral patellar dislocation due to the high incidence of recurrent
      instability following conservative management. Anatomic reconstruction of the
      MPFL minimizes graft length changes during full knee range of motion and restores
      patellar stability. MATERIALS & METHODS: Four fresh frozen cadaver specimens
      underwent biomechanical testing in a materials testing machine. With the knee
      fixed in 30 degrees  of flexion, the patella was translated laterally a distance
      of 10 mm and continuous force-displace- ment data was collected with the intact
      MPFL and again following a newly described MPFL reconstruction technique. Lateral
      force-displacement and stiffness data were calculated, allowing comparison
      between the intact and reconstructed MPFL. RESULTS: The average lateral
      restraining force provided by the intact MPFL was 10.6 +/- 5.7, 36.6 +/- 2.7, and
      69.0 +/- 5.9 N while the lateral restraining force following MPFL reconstruction
      was 0.4 +/- 4.3, 50.3 +/- 16.3, and 110.2 +/- 17.5 N at 1, 5, and 10 mm of
      lateral displacement, respectively. CONCLUSION: Anatomic MPFL reconstruction
      displays similar lateral restraining force compared to the intact MPFL at low
      levels of lateral displacement. At higher levels of displacement, the
      reconstructed MPFL provides increased lateral restraining force compared to the
      intact MPFL, improving patellar stability in pathologic knees.

PMID- 24027464
TI  - Effect of ACL reconstruction graft size on simulated Lachman testing: a finite
      element analysis.
AB  - INTRODUCTION: ACL reconstructions are frequently performed following ACL injury.
      The most common treatment is single bundle reconstruction. While ACL
      reconstructions have been studied clinically and experimentally, quantitative
      information regarding the local biomechanics the knee following ACL
      reconstruction is generally lacking. Specifically, the role of graft size on
      joint stability and soft tissue injury propensity is currently unknown. METHODS:
      Therefore, a non-linear contact finite element model was developed to
      systematically evaluate the relationship between ACL graft size and knee joint
      biomechanics following ACL reconstruction. A simulated Lachman maneuver was
      utilized to assess knee joint laxity, meniscal stress, in situ graft loading, and
      peak articular cartilage contact pressure for ACL graft sizes between 5 and 9 mm,
      as well as an ACL-deficient knee. The model was validated by corroboration with
      previously published experimental (cadaveric) data on ACL reconstruction.
      RESULTS: The 5 mm graft resulted in 30% greater relative AP translation compared
      to the 9 mm graft; the ACL deficient knee resulted in 2.56-times greater AP
      translation than the average graft reconstruction. Contact pressure and peak
      meniscal stresses decreased monotonically for increased values of ACL graft
      diameter. For all graft diameters, soft tissue stress and articular contact
      pressure was reduced versus the ACL-deficient knee. CONCLUSIONS: ACL
      reconstruction dramatically affects the local biomechanics of the knee. Stresses
      occurring in the soft tissues, as well as contact pressure at the articular
      surfaces, were found to be highly sensitive to ACL graft size. Larger grafts were
      associated with lower meniscal stress, decreased joint laxity, and less articular
      cartilage contact stress. Therefore, the current data suggests that increased
      graft size confers a biomechanical advantage in the ACL reconstructed knee.

PMID- 24027465
TI  - Arthroscopic validation of the clinical exam for the detection of the symptomatic
      synovial-plical complex by relief from surgical excision.
AB  - PURPOSE: The goal is to introduce a reproducible exam technique that allows
      clinical diagnosis of symptomatic plical bands and associated synovium about the
      knee. We then aimed to assess the accuracy of the exam technique through
      arthroscopic confirmation of these tissues. Lastly, we hope to determine whether
      arthroscopic plicectomy and partial synovectomy is an effective treatment for
      alleviating the pain associated with symptomatic plica. METHODS: This
      retrospective study evaluated 80 consecutive symptomatic knees under the care of
      a single physician diagnosed with symptomatic plica and associated painful
      synovium from 2001-2011. These patients underwent diagnostic and therapeutic
      arthroscopy to verify the presence of a plica and painful synovium with
      plicectomy and partial synovectomy if necessary. Statistical analysis was
      performed to determine the sensitivity and positive predictive value of the exam.
      RESULTS: The medial parapatellar region was the most common location for
      symptomatic plica and associated synovial tissue. The exam technique described in
      this study had a sensitivity of 83.8% with a positive predictive value of 98.6%
      in the specific patient population described. CONCLUSIONS: This study suggests
      that while the medial plical band is the most common, there is frequently
      sensitive synovial tissue found in multiple locations about the knee. This study
      also suggests that a thorough exam technique can accurately diagnose both the
      plical bands as well as the sensitive synovial tissue. LEVEL OF EVIDENCE: Level
      II, Diagnostic Study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 24027466
TI  - A clinical and radiographic approach for establishing proper tibial tubercle
      transfer when using quad active femoral nerve stimulation.
AB  - BACKGROUND: The tibial tubercle-trochlear groove measurement (TT-TG), which
      measures the lateral offset of the tibial tubercle relative to the trochlear
      groove of the femur, has been utilized as an intraoperative tool to help
      establish maximum patellofemoral congruency in patients who suffer from patellar
      instability. We have previously published our approach of establishing how far to
      transfer the tibial tubercle using intraoperative femoral nerve stimulation in
      order to achieve congruency from 0-30 degrees  of flexion. The technique and
      clinical outcomes have previously been published in this journal and elsewhere.
      Here we describe the use of the TT-TG distance to determine how far to transfer
      the tibial tubercle to achieve our goals and have found that it varies according
      to the clinical exam features. PURPOSE: We intended to determine the
      effectiveness of using the preoperatively established TT-TG to predict the degree
      of intraoperative me- dialization of the tibial tubercle to achieve our goal of
      establishing dynamic congruency of the patella in the trochlear groove when using
      the previously described femoral nerve stimulation method of estimating dynamic
      tracking of the patella. METHODS: From the study group of patients used in other
      publications, we examined 20 knees in 18 patients who had a history of recurrent
      lateral dislocations and underwent a Fulkerson tibial tubercle transfer. Each
      knee was dynamically assessed preoperatively by obtaining an MRI at 30 degrees 
      of flexion and complete hyperextension while voluntarily contracting their
      quadriceps. These were then compared to the intraoperative transfer of the tibial
      tubercle required to achieve maximum congruency when the femoral nerve was
      stimulated. We then looked at the preoperative TT-TG measurement to determine its
      role in predicting what was required at achieving congruency in the context of
      the quad active MRI findings. RESULTS: Thirteen knees preoperatively demonstrated
      a positive J-sign defined as the patella subluxated greater than or equal to 5 mm
      lateral in full extension compared to 30 degrees  of flexion. In these patients,
      the TT-TG was accurate if the distance medialized was 1:1 with the measured TT
      TG. In 7 out of the 20 knees, the patella demonstrated a false negative J-sign
      where the patella was radio- graphically subluxated at 30 degrees  of flexion as
      well as at hyperextension. In this group, the TT-TG underestimated the transfer
      required for congruency on average 5mm even when using the 1:1 ratio.
      CONCLUSIONS: The preoperative use of the J-sign is of value when determining the
      role of the TT-TG measurement and estimating the distance required to
      intraoperatively achieve congruency when using the femoral nerve stimulation
      technique. Those that demonstrated a positive J-sign of 5mm or greater, a 1:1
      ratio of TT-TG to medialization is most reliable at establishing congruency of
      the patellofemoral joint. Whereas, those that demonstrated a false negative J
      sign even the 1:1 ratio remains inadequate at producing congruency and more
      medialization is required. LEVEL OF EVIDENCE: Level III, Retrospective
      Observational/Comparative Study.

PMID- 24027467
TI  - Southwick-Fulkerson Osteotomy with intraoperative femoral nerve guidance.
AB  - BACKGROUND: Patellofemoral instability is a complex problem with most previous
      treatment plans addressing static alignment and static stabilizers. Although the
      quadriceps muscles are known to affect the tracking of the patella, they are
      rarely taken into account during a surgical procedure. PURPOSE: The purpose of
      this study is to determine the two year minimum results of 37 knees which
      received a Southwick-Fulkerson Osteotomy and MPFL repair or reconstruction both
      under the guidance of femoral nerve stimulation. METHODS: Patients underwent a
      Southwick-Fulkerson Osteotomy and either medial patellofemoral ligament (MPFL)
      repair or reconstruction using femoral nerve stimulation as a means of dynamic
      intraoperative evaluation of patello-femoral congruity in terminal extension. Two
      year minimum outcomes of 26 patients, 31 knees (84% return rate) were evaluated
      using KOOS and IKDC scores, and physical exam features of apprehension and
      assessment of dynamic tracking in the last 30 degrees of knee extension.
      Variables were evaluated with t-tests and ANOVA. RESULTS: 29/31 knees reported
      they were happy with the procedure and reported they would do it again. One knee
      (3%) reportedly "redislocated", but did not return for verification by exam.
      30/31 had non-pathologic tracking. One knee displayed a small but residual J
      sign. 4/16 knees with MPFL repair only and 0/15 with MPFL repair and
      reconstruction exhibited a positive apprehension sign. Increased age and
      apprehension were correlated with lower outcome scores. CONCLUSIONS:
      Intraoperative femoral nerve stimulation is an effective way of evaluating
      patellar tracking intraoperatively that leads to 97% stable patellae with near
      congruent patello-femoral tracking. MPFL reconstruction is superior to MPFL
      repair in eliminating the persistence of the apprehension sign.

PMID- 24027468
TI  - Single-bundle versus double-bundle ACL reconstructions in isolation and in
      conjunction with extra-articular iliotibial band tenodesis.
AB  - BACKGROUND: Intra-articular anterior cruciate ligament (ACL) reconstruction has
      been the primary treatment option for isolated ACL injuries for many years. An
      anatomic double-bundle reconstruction has been devised in an effort to improve
      rotational control. The role of the extra-articular iliotibial band tenodesis in
      ACL injuries has evolved from primary treatment, to an adjuvant secondary
      procedure, to being used more selectively in revision ACL reconstructions.
      HYPOTHESES: 1) Single-bundle and doublebundle intra-articular ACL reconstructions
      will both restore pre-injury laxity measurements in an isolated ACL injury
      cadaver model. 2) The deep iliotibial band structures contribute to rotational
      control and in a dual ACL + ITB injury cadaver model, ACL reconstruction alone
      cannot restore rotational control. STUDY DESIGN: Controlled Laboratory Design.
      METHODS: 17 fresh frozen cadavers received intra-articular reconstructions, seven
      single-bundle and ten double-bundle; laxity was measured with the ACL intact/ITB
      intact, ACL reconstructed/ITB intact, after cutting the ITB, and after an ITB
      tenodesis procedure; laxity measurements of anterior tibial translation(ATT) and
      internal rotation(IR) were measured following applications of an anterior shear
      force, an internal torque and a coupled anterior shear force-internal torque at
      30 and 90 degrees of flexion. RESULTS: Single-bundle and double-bundle ACL
      reconstructions both restored IR to a native knee state under isolated internal
      torques and under coupled forces. Both reconstruction techniques also re
      established anterior tibial translation to at least the pre-ACL injury level,
      with over-constraint in the double-bundle subgroup [5.00 (+2.11) to 3.50(+1.18),
      p-value 0.026] under coupled loads at 30 degrees of flexion. With the individual
      ACL reconstructions held constant, under coupled forces mean IR increased in the
      single-bundle subgroup [13.7(+1.1) to 17.6(+1.2), p-value 0.004] and the double
      bundle subgroup [9.5(+1.0) to 12.4(+1.0), p-value 0.009] with the cutting of the
      ITB at 30 degrees. Under internal torque, mean IR increased in the single-bundle
      subgroup [14.0(+1.0) to 18.4(+1.6), p-value 0.016] with the cutting of the ITB at
      30 degrees, while IR increased in the double-bundle subgroup [10.0(+1.3) to
      13.4(+1.5), p-value 0.002] under the same internal torque at 90 degrees. With the
      ACL reconstruction held constant, ATT did not significantly change when the ITB
      was cut or when it was tenodesed under any specific loading condition.
      CONCLUSION: Single-bundle and double-bundle intra-articular reconstructions were
      both able to restore internal rotation and anterior tibial translation to at
      least native knee laxity levels after an isolated laboratory ACL injury. When the
      ACL reconstructions were held constant, internal rotation statistically increased
      with the cutting of the ITB under multiple testing conditions in both the single
      bundle and double-bundle subgroups.

PMID- 24027469
TI  - Survey of high school athletic programs in Iowa regarding infections and
      infection prevention policies and practices.
AB  - OBJECTIVE: To assess high school athletic programs' infection prevention policies
      and procedures and to estimate the frequency of skin and soft tissue infections
      (SSTIs) among Iowa's high school athletes. METHODS: An on-line survey of high
      school athletic programs. RESULTS: Nearly 60% of programs responded. Schools in
      higher classifications were more likely to have a certified athletic trainer (AT;
      P < 0.0001) and to report that they had a policy preventing athletes with SSTIs
      from participating in athletic events than were schools in lower classifications
      (P = 0.0002). Programs that had an AT reported that athletic training equipment
      (P = 0.01) and tables (P = 0.02) were cleaned more frequently than did programs
      without ATs. Programs were significantly more likely to provide training
      equipment than to provide soap or towels. About 57% of programs reported that at
      least one athlete acquired an SSTI during the prior school year, including
      methicillin- resistant Staphylococcus aureus (N = 14; 10.8%). Programs that had
      an AT (P = 0.02) were in higher classifications (P < 0.0001), educated athletes
      about SSTIs (P < 0.0001), or had policies regarding athletes with SSTIs (P =
      0.01) were more likely than other programs to report having at least one athlete
      with an SSTI. The estimated SSTI rate per 1000 athletes ranged from 22.0 in 1A to
      5.9 in 4A programs. CONCLUSIONS: SSTIs are common among Iowa's high school
      athletes. Staff should review and update their infection prevention policies.
      Athletic programs need resources to support infection prevention efforts.

PMID- 24027470
TI  - Serum protein electrophoresis in the evaluation of lytic bone lesions.
AB  - Serum protein electrophoresis (SPEP) is often obtained at the initial evaluation
      of a radiolucent bone lesion of unknown etiology. The results are considered
      convincing evidence of the presence or absence of a plasma cell neoplasm. The
      sensitivity and specificity of the SPEP have not been reported in this clinical
      scenario. Our purpose is to assess the diagnostic value of the SPEP in the
      initial work-up of the radiolucent bone lesion. We identified 182 patients
      undergoing evaluation of a radiolucent bone lesion that included tissue biopsy
      and an SPEP value. We then calculated the sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value (NPV) of SPEP as a
      diagnostic test for a plasma cell neoplasm in this clinical scenario. Forty-six
      of 182 (25.3%) patients in our series were diagnosed with a plasma cell neoplasm
      by histopathologic analysis. The sensitivity of SPEP was 71% and the specificity
      was 83%. PPV was 47% and NPV was 94%. When analyzing only those presenting with
      multiple lesions, the percentage of patients diagnosed with multiple myeloma
      increased to 44.7% (34 of 76 patients). The SPEP, however, did not have a
      substantially increased diagnostic accuracy with sensitivity of 71%, specificity
      79%, PPV 40% and NPV 93%. SPEP lacks sensitivity and positive predictive value to
      provide a definitive diagnosis of myeloma in radiolucent bone lesions, but has a
      high negative predictive value which may make it useful in ruling out the
      disease. We recommend that this test either be performed in conjunction with
      urine electrophoresis, immunofixation electro-phoresis and free light chain
      assay, or after biopsy confirming the diagnosis of myeloma.

PMID- 24027471
TI  - Factors affecting outcomes in patients treated surgically for upper extremity
      tumors and tumor-like lesions.
AB  - There is little data available regarding outcomes of patients who have undergone
      surgery for tumors of the upper extremity. Functional data after surgery for
      upper extremity tumors would aid in guiding patient expectations in the peri
      operative period. The purpose of this study was to identify patient, tumor, and
      surgery-related characteristics associated with patient-reported physical and
      emotional function before and after surgery for tumors of the upper extremity.
      Pre- and post-operative mental and physical Medical Outcomes Study Short Form 36
      (SF-36) scores were collected from 79 patients with benign and malignant
      neoplasms of the upper extremity. A retrospective chart review was performed to
      ascertain whether tumor behavior, type, location, patient sex, age, surgical
      specimen size, or type of surgery were correlated with differing outcomes. Our
      outcome measure was patient-reported physical and mental score (SF-36) at less
      than one year, one to two years, and greater than two years post-operatively. We
      found that patients with tumors proximal to the elbow and patients with right
      sided tumors had statistically significantly lower post-operative physical scores
      at minimum two-year follow-up (p=0.02). Additionally, lower physical scores were
      associated with age greater than 50 (p=0.03) and tumor resection rather than
      curettage (p=0.01). The subset of patients with hereditary multiple exostoses had
      significantly lower post-operative physical scores than other patient sub
      populations. There was no difference in physical function after surgery between
      patients with benign and malignant tumors, patients with tumors larger than 5 cm
      and less than 5 cm in greatest dimension, and patients with bone versus soft
      tissue tumors. Interestingly, we found that there was no difference in mental
      function scores between any comparisons. Our results suggest that patient age,
      tumor location, and type of surgery are correlated with patient-reported physical
      function following surgery. These findings could be helpful in counseling
      patients undergoing surgery for tumors of the upper extremity. 

PMID- 24027472
TI  - Is hospital teaching status a key factor in hospital charge for children with hip
      fractures?: preliminary findings from KID database.
AB  - OBJECTIVE: Proximal femur fractures cause significant pain and economic cost
      among pediatric patients. The purposes of this study were (a) to evaluate the
      distribution by hospital type (teaching hospital vs non-teaching hospital) of
      U.S. pediatric patients aged 1-20 years who were hospitalized with a closed hip
      fracture and (b) to discern the mean hospital charge and hospital length of stay
      after employing propensity score to reduce selection bias. METHODS: The 2006
      Healthcare Cost and Utilization Project (HCUP) Kids' Inpatient Database (KID) was
      queried for children aged up to 20 years that had principle diagnosis of hip
      fracture injury. Hip fractures were defined by International Classification of
      Diseases, 9th Revision, Clinical Modification codes 820.0, 820.2 and 820.8 under
      Section "Injury and Poisoning (800-999)" with principle internal fixation
      procedure codes 78.55, 79.15 and 79.35. Patient demographics and hospital status
      were presented and analyzed. Differences in mean hospital charge and hospital
      length of stay by hospital teaching status were assessed via two propensity score
      based methods. RESULTS: In total, 1,827 patients were nation-ally included for
      analysis: 1,392 (76.2%) were treated at a teaching hospital and 435 (23.8%) were
      treated at a non-teaching hospital. The average age of the patients was 12.88
      years old in teaching hospitals vs 14.33 years old in nonteaching hospitals. The
      propensity score based adjustment method showed mean hospital charge was $34,779
      in teaching hospitals and $32,891 in the non-teaching hospitals, but these
      differences were not significant (p=0.2940). Likewise, mean length of hospital
      stay was 4.1 days in teaching hospitals and 3.89 days in non-teaching hospitals,
      but these differences were also not significant (p=0.4220). CONCLUSIONS: Hospital
      teaching status did not affect length of stay or total hospital costs in children
      treated surgically for proximal femur fractures. Future research should be
      directed at identifying factors associated with variations in hospital charge and
      length of stay.

PMID- 24027473
TI  - Management of idiopathic clubfoot after formal training in the Ponseti method: a
      multi-year, international survey.
AB  - BACKGROUND: Over the past decade, the Ponseti method has become the standard of
      care to treat clubfoot amongst orthopaedic surgeons around the world. Since 2001,
      the University of Iowa, under the guidance of the late Dr. Ignacio Ponseti, has
      been teaching the Ponseti method through a standardized training course. This
      study examines the current clubfoot management practices of those who have
      participated in the course and the effectiveness of formal Ponseti Training
      Courses. METHODS: An online survey was administered to practitioners who
      participated in the University of Iowa Ponseti Training Course from 2001-2011.
      RESULTS: One hundred and thirty-one practitioners responded to the survey
      representing 33 different countries and 70 different orthopaedic societies.
      Ninety-seven percent of practitioners reported currently using the Ponseti method
      as the preferred treatment for clubfoot. The respondents reported the average
      duration of each cast was 9.21 days (SD=9.04 d) and the average cast phase of
      treatment lasted 7.62 weeks (SD=2.43 w). Physicians were responsible for applying
      the cast 79% of the time. Braces were utilized following casting by 96% of
      physicians. The average age of brace use was 41 months (SD=16 m). The reported
      relapse rate was 21% (SD=17%). Ninety-seven percent of practitioners changed
      their practice after completion of the course. The preferred method prior to the
      course was surgical release (48%). Sixty-one percent of practitioners preferred
      review articles as an additional educational support; 49% preferred training
      videos. Sixty-seven percent believed an 'on-site' visit to their hospital by an
      expert in the Ponseti method would be very beneficial. Seventy-three percent
      suggested improving the course by providing more 'hands on' experience. Ninety
      five percent of practitioners were satisfied with the course. CONCLUSION: The
      Ponseti Training Course is an effective way to educate physicians on how to treat
      clubfoot with the Ponseti method. However, improvements should include more hands
      on learning as well as an 'on-site' visit with an expert Ponseti practitioner.

PMID- 24027474
TI  - Managing uncertainty in the context of clubfoot care: exploring the value of
      uncertainty management theory and the sense of virtual community.
AB  - Serious health conditions, such as clubfoot, could be a major source of
      uncertainty and stress for parents of children affected. How parents deal with
      uncertainty and stress as related to their child's health condition is of
      interest for medical professionals and health communicators alike. While
      physicians remain a preferred source of health information, during medical
      encounters or via phone and email communication, many individuals seek out health
      information on the Internet, including in online support communities. This study
      explored the connections between Uncertainty Management Theory (UMT) constructs
      and the potential contribution of the sense of virtual community (SOVC) to the
      UMT framework. The results of this research suggest that the UMT needs to be
      adapted for use in online contexts. One way is to include theoretical constructs,
      such as the sense of virtual community, specifically developed to measure online
      interactions. A modified and updated Uncertainty Management Theory could be
      useful in exploring, analyzing and understanding online behaviors related to
      health conditions such as clubfoot and thus contribute substantially to what we
      know about caregivers in their role as uncertainty managers. 

PMID- 24027475
TI  - Understanding the knowledge and perceptions about clubfoot in Karachi, Pakistan:
      a qualitative exploration.
AB  - This paper explores local knowledge and perceptions about clubfoot in the Indus
      Hospital's catchment population in Karachi, Pakistan. Data was collected through
      seven focus group discussions with community members and Lady Health Workers,
      nine in-depth interviews with parents of children with treated or untreated
      clubfoot, and one interview with an adult with untreated clubfoot. We found that
      participants were unable to distinguish clubfoot from other disabilities.
      Moreover, participants had a number of beliefs about the causes of clubfoot,
      which included lunar and solar eclipses, religious explanations, the health
      status and behaviours of parents, and genetics. While participants were aware of
      surgery and other allopathic treatments for clubfoot, many also believed in
      traditional and religious treatments or were unaware that clubfoot is a treatable
      condition. This study is the first of its kind in Pakistan and provides important
      insights that clubfoot programs need comprehensive strategies to raise awareness
      about clubfoot amongst community members, health providers, and religious leaders
      in order to be successful. 

PMID- 24027476
TI  - Early effects of a 'train the trainer' approach to Ponseti method dissemination:
      a case study of Sri Lanka.
AB  - BACKGROUND: The Ponseti method has been established as the standard of care for
      the treatment of clubfoot in many developed countries for its utility, cost
      effectiveness, and efficiency. However, despite its being described as the gold
      standard for clubfoot treatment, there are still many areas of the world bereft
      in formal training in the Ponseti method. This is especially important since 80%
      of patients with clubfoot are born in developing countries where the need is the
      greater for experienced providers. This study analyzes a 'Train the Trainer'
      approach, specifically in the island nation of Sri Lanka, as a model for future
      dissemination of the Ponseti method throughout the developing world. METHODS: A
      rapid ethnographic study design that included interviews, focus groups, and
      direct observation of 162 patients and healthcare practitioners directly involved
      with clubfoot care was conducted. RESULTS: The average age of the patients at the
      time of the interview was 75.4 weeks old (SD = 149.2), traveled 45.2 kilometers
      (SD = 49.8) to receive their care, and received 4 casts (SD = 2.2) for correction
      of the deformity. Since the initiation of the 'Train the Trainer' educational
      program, clubfoot clinics reportedly grew from 6-7 patients per week to over 60
      patients per week. The majority of this patient population growth was attributed
      to word of mouth. Major barriers to the method included casting materials,
      bracing materials, and a lack of a dedicated area of the clinic to conduct
      tenotomies under local anesthesia. Of note, cost was not cited as a major
      barrier. CONCLUSION: Early evaluation suggests great utility of the 'Train the
      Trainer' method - especially regarding an increased patient demand for treatment.
      However, further studies are necessary to understand the long-term utility of
      this training methodology.

PMID- 24027477
TI  - The Ponseti method of treatment for clubfoot in Brazil: barriers to bracing
      compliance.
AB  - BACKGROUND: Clubfoot is the most common extremity birth defect. It causes the
      feet of affected individuals to point inward and downward, preventing them from
      walking normally. Neglected clubfoot causes disabilities that result in a lack of
      social integration, creating a psychological and financial burden for the family
      and community. Clubfoot has been effectively treated through the Ponseti method,
      a treatment utilizing serial casts to correct the deformity followed by use of an
      abduction brace for approximately 2-4 years. sustained use of the brace is
      necessary to prevent relapse and ensure a successful outcome. Brace compliance in
      the setting of limited resources in the developing world can be challenging. The
      purpose of this study was to identify the barriers to bracing compliance in
      southeastern Brazil. In addition to socioeconomic and cultural barriers, this
      study also looked at improper prescribing practices by physicians as a potential
      cause of noncompliance. The study sought to identify the role of physician
      education in the use of the Ponseti method and physicians' knowledge of the
      bracing process. PURPOSE OF THE STUDY: Identify the barriers to bracing adherence
      that could negatively impact the treatment of children with clubfoot. METHODS:
      Forty-five orthopedists from several centers in southeastern Brazil were
      interviewed. Physicians were asked about their training in the Ponseti method,
      their protocol when prescribing the brace, their evaluation of its importance,
      and a series of open-ended questions designed to identify the positive and
      negative qualities of local braces. They were also asked what they perceived to
      be the biggest challenges to sustained brace use. RESULTS: sixteen of the
      physicians interviewed were orthopedic residents, and 29 had completed their
      residencies. Of these two groups, only 25% and 65%, respectively, appropriately
      prescribe the abduction brace for patients, with the majority recommending use of
      the brace for an inadequate period of time. The high costs and delays in
      acquisition of the brace and a lack of orthopedic stores able to adequately
      construct the orthotic, also present considerable barriers to sustained brace
      use. CONCLUSIONS: Many of the causes of noncompliance with bracing protocol stem
      from systemic inequities and challenges, rather than a lack of collaboration from
      the families themselves. Furthermore, insufficient prescription of the brace by
      physicians may represent a major barrier to bracing compliance in southeastern
      Brazil. This research indicates a need to evaluate physician training and
      continuing medical education in order to ensure that physicians are adequately
      utilizing the brace.

PMID- 24027478
TI  - Descriptive epidemiology of clubfoot in Peru: a clinic-based study.
AB  - congenital clubfoot is the most common birth defect of the musculoskeletal system
      and affects 1 in every 1000 live births each year.(1) Although there have been
      numerous studies of investigation, the etiology and pathogenesis of clubfoot
      remains unknown. To date, no epidemiological studies have been conducted in Peru
      to assess possible genetic and environmental risk factors associated with this
      deformity. The purpose of this study was to evaluate specific environmental and
      socioeconomic factors that may increase the risk of clubfoot. A descriptive
      clinic-based study was conducted using structured questionnaires given to
      biological mothers of clinically confirmed clubfoot patients (n=72) and
      biological mothers of children between ages 0-18 with no first or second degree
      family history of clubfoot as controls (n=103). Phenotypic data from clubfoot
      subjects were also collected. We found that males were twice as likely to have
      clubfoot as females, and half of all clubfoot patients had bilateral clubfoot.
      There was no significant difference in the rate of left vs. right clubfoot.
      Infant birth in the winter months correlated with an increased risk of clubfoot
      (p=0.01476). Maternal characteristics found to be significantly associated with
      increased risk of clubfoot were young maternal age at conception (p=0.04369) and
      low maternal education (p=0.003245). Young paternal age also had a correlation
      with increased risk of clubfoot in the child (p=0.0371). Both paternal smoking
      (p=0.00001) and the presence of any household smoking (p=0.00003) were strongly
      associated with an increased risk of clubfoot. 

PMID- 24027479
TI  - Barriers to the Ponseti method in Peru: a two-year follow-up.
AB  - Idiopathic clubfoot affects approximately 100,000 children each year and is one
      of the leading causes of disability worldwide. The Ponseti method is an
      inexpensive, non-surgical treatment that, when executed correctly, is more than
      95% effective; however, in Peru, a developing country where a low-cost
      alternative is greatly needed, physicians report up to 30% of patients do not
      complete treatment. This study involved semi-structured interviews with 25
      physicians who practice the Ponseti Method in Peru to discuss obstacles for the
      method in their country. The most frequent obstacles to the Ponseti method in
      Peru reported by physicians included lack of physicians trained in the Ponseti
      method in the country, patient transportation and distance to treatment centers,
      and lack of parental knowledge of the Ponseti method. These data suggest the need
      to train more physicians in Peru, particularly in the provinces. Increasing
      access to trained physicians in provincial areas may reduce the financial and
      travel burden of parents to help increase compliance with treatment. 

PMID- 24027480
TI  - Development of an orthopaedic surgical skills curriculum for post-graduate year
      one resident learners - the University of Iowa experience.
AB  - Orthopaedic surgery requires a high degree of technical skill. Current
      orthopaedic surgical education is based largely on an apprenticeship model. In
      addition to mounting evidence of the value of simulation, recent mandated
      requirements will undoubtedly lead to increased emphasis on surgical skills and
      simulation training. The University of Iowa's Department of Orthopaedic Surgery
      has created and implemented a month long surgical skills training program for PGY
      1 residents. The goal of the program was to improve the basic surgical skills of
      six PGY-1 orthopaedic surgery residents and prepare them for future operative
      experiences. A modular curriculum was created by members of the orthopaedic
      faculty which encompassed basic skills felt to be important to the general
      orthopaedic surgeon. For each module multiple assessment techniques were utilized
      to provide constructive critique, identify errors and enhance the performance
      intensity of trainees. Based on feedback and debriefing surveys, the resident
      trainees were unanimously satisfied with the content of the surgical skills
      month, and felt it should remain a permanent part of our educational program.
      This manuscript will describe the development of the curriculum, the execution of
      the actual skills sessions and analysis of feedback from the residents and share
      valuable lessons learned and insights for future skills programs. 

PMID- 24027481
TI  - How orthopaedic residents perceive educational resources.
AB  - INTRODUCTION: The educational paradigm for orthopaedic surgeons is shifting from
      a strictly Operating Room based approach to the addition of simulator- and lab
      based models. This study aims to assess resident views on the relative value of
      orthopaedic educational resources and the value of a cadaver-based arthroscopy
      skills laboratory. METHOD: A questionnaire assessing beliefs about various
      orthopaedic educational resources for overall orthopaedic education and surgical
      skills education was given to all residents in one orthopaedic residency program
      with a new arthroscopic skills laboratory during a three year period. Forty-one
      orthopaedic residents from years PGY1 through PGY5 participated. RESULTS:
      Observation and participation in the OR was the highest ranked learning activity
      for both overall and surgical skills education. Sessions in the skills lab ranked
      second for surgical skills education and fourth for overall orthopaedic
      education. The arthroscopic skills lab was most highly valued for practicing 3-D
      use of instruments and developing familiarity with equipment. CONCLUSIONS:
      Orthopaedic trainees highly value operating room experience as the primary
      resource for education during residency. Orthopaedic trainees have found the
      addition of a surgical skills training lab for teaching arthroscopic skills a
      significant benefit to both their overall education and to surgical skills
      training.

PMID- 24027482
TI  - Technique tip: percutaneous endoscopically-assisted calcaneal slide osteotomy.

PMID- 24027483
TI  - Toward improved clinical relevance of cartilage insult models in the rabbit knee:
      surgical access to the habitual weight-bearing region.
AB  - OBJECTIVE: This article addresses considerations for using a posterior
      (popliteal) instead of anterior (para-patellar) approach for experimental insult
      to the rabbit knee medial femoral condyle (MFC) surface in vivo. The posterior
      approach is particularly advantageous when intending to address the
      pathomechanisms of OA associated with habitual cartilage loading, or the efficacy
      of a cartilage repair method, in a clinically relevant experimental setting.
      DESIGN: Studies using anterior versus posterior approaches for such purposes in
      survival rabbit models of the MFC articular surface insults were systematically
      surveyed. The anterior-posterior span of the primary weight-bearing region of
      that surface was demonstrated cadaverically. RESULTS: Of a total of 31 papers
      identified in 2007-2012, an anterior approach was utilized in 28 studies (> 90%).
      More than half (17/28) explicitly regarded the cranial half (inferior aspect) of
      the MFC surface as being a "weight-bearing" region. The insult site through
      anterior approach (identified in figures) was located in the cranial half region
      in all cases. Cadaverically, however, the center of habitual tibio-femoral
      contact locations on the MFC surface was located in the caudal half region
      (posterior aspect) of the MFC surface. The majority of the habitual contact
      region was accessible only by a posterior surgical approach. CONCLUSION: For the
      above-noted purposes, use of a posterior (popliteal) approach, rather than an
      anterior approach, is highly recommended.

PMID- 24027485
TI  - Intravenous versus oral outpatient antibiotic therapy for pediatric acute
      osteomyelitis.
AB  - The optimal route (oral versus intravenous) of antibiotic administration for
      pediatric acute osteomyelitis is not well established. Seventy-eight children
      from our university hospital and 17 children at our county hospital were treated
      for acute osteomyelitis. The rates of intravenous antibiotics upon discharge were
      95% versus 65% (P=0.002), respectively. The recurrence rate and line complication
      rates were 10% and 24% at the university hospital, compared to 0% (P=0.34) and 6%
      (P=0.29) at the county hospital. Based on this data, a prospective comparison
      between intravenous and early oral antibiotic therapy for pediatric acute
      osteomyelitis is recommended. 

PMID- 24027484
TI  - Nerve injury and pain after operative repair of calcaneal fractures: a literature
      review.
AB  - Peripheral nerve injury is a common problem in foot and ankle surgery. We look at
      evidence of nerve injury as it relates to different operative approaches to the
      fractured calcaneus. The direct lateral, extended lateral, smile, sinus tarsi,
      and percutaneous approaches are discussed and the reported incidence of nerve
      injury in each is identified. We expect to identify divergent rates of injury
      between approaches and stimulate further investigation into prevention and
      treatment. 

PMID- 24027486
TI  - Secondary chondrosarcoma of the pelvis arising from a solitary exostosis in an 11
      year-old patient: a case report with 5-year follow-up.
AB  - Although conversion of an osteochondroma to chondrosarcoma is a well-described
      rare occurrence, it is usually associated with syndromes such as multiple
      hereditary exostoses and is much more common after maturity. We present here a
      rare case of secondary pelvic chondrosarcoma arising from a solitary exostosis in
      a pediatric patient. An 11-year-old, otherwise healthy, female was referred to
      our clinic for evaluation of a pelvic mass detected on a radiograph. The
      radiographs obtained by the referring physician demonstrated a large lesion
      arising from the right superior pubic ramus, which was visible but not identified
      on an abdominal radiograph several years prior. Histopathologic analysis showed
      chondrosarcoma which was supported by an additional opinion to rule out
      chondroblastic osteosarcoma. The patient was treated with wide resection without
      adjuvant therapy and is doing well with no evidence of recurrence five years post
      operatively. There have been only a few small case series describing
      chondrosarcoma in the pediatric patient. Even rarer are descriptions of secondary
      chondrosarcoma with only occasional cases reported as part of larger case series.
      Chondrosarcoma is a rare and difficult diagnosis in the pediatric patient. There
      is often considerable debate between chondrosarcoma and chondroblastic
      osteosarcoma, and the treatment implications of differentiating these diagnoses
      are of paramount importance. 

PMID- 24027487
TI  - Does lateral knee geometry influence bone bruise patterns after anterior cruciate
      ligament injury? A report of two cases.
AB  - Bone bruise patterns are commonly seen after acute anterior cruciate ligament
      injuries; they represent a subchondral impaction injury that occurs in the
      lateral knee joint between the mid-lateral femoral condyle and the posterior
      lateral tibial plateau. These contusion patterns are present in the majority of
      noncontact ACL injuries. These injury patterns vary significantly in severity and
      this aspect is poorly understood. Edema patterns have gained increased interest
      in the literature of late; they may indicate the severity of the initial injury.
      They also may be correlated with the development of subsequent osteochondral
      defects and osteoarthritis. Given the location of this subchondral injury, it is
      plausible to assume that the geometry of the lateral femorotibial joint may play
      a role in ACL injury mechanism and severity of injury. We are reporting two cases
      of clinically identical ACL injuries. A patient with a flat lateral tibial
      plateau was noted to have a much larger bone edema pattern than a second patient
      with the highly convex lateral tibial plateau. This may shed light on the
      pathomechanics of ACL injury and suggests that an individual with a relatively
      flat tibial plateau has a stable lateral knee joint. Therefore, we hypothesize
      that much greater force is required to dislocate a flat and stable lateral
      femorotibial joint in a pivot shift pattern to produce an ACL injury. The greater
      force required results in a large bone edema pattern. Conversely, the individual
      with a relatively short and convex tibial plateau has an inherently unstable
      lateral joint and relatively smaller amounts of force would be needed to produce
      the identical injury to the ACL. As less force is required, smaller bone edema
      patterns result. 

PMID- 24027489
TI  - Roundworm-associated median nerve compression: a case report.
AB  - Human dirofilariasis is a rare zoonotic infection caused by the bite of a blood
      feeding mosquito infected with a filarial nematode (roundworm). these infections
      can manifest as stationary or migratory subcutaneous or conjunctival nodules. We
      report an unusual case of Dirofilaria tenuis (D.tenuis) infection that developed
      into a space- occupying lesion in the wrist leading to median nerve compression
      pathology in an otherwise healthy young woman. We also comment on the natural
      history of the disease and report the outcome after surgical excision. To our
      knowledge, we are the first to report a case of median nerve compression caused
      by a growing subcutaneous nodule from a D.tenuis infection. 

PMID- 24027488
TI  - Spontaneous reduction of a chronic radial head subluxation after open reduction
      and percutaneous pin fixation of a radial neck fracture: a case report and review
      of the literature.
AB  - BACKGROUND: Fractures of the radial neck in children have shown to account for 5
      10% of traumatic elbow injuries in the pediatric population. Chronic dislocation
      of the radial head with concomitant fracture has been shown to result in
      progressive deformity and unacceptable loss of motion. METHODS: In this case
      report, we describe a patient who sustained a type 2 radial neck fracture with
      100% displacement. The patient's clinical and surgical management will be
      discussed and a review of the literature is provided as it relates to this
      particular case. RESULTS: The patient underwent open reduction and percutaneous
      pin fixation of her displaced, dislocated left radial neck fracture in the
      operating room after multiple failed attempts at closed reduction due to
      interposition of the annular ligament. Three months after her operation
      radiographs revealed a well-healed radial neck with no signs of avascular
      necrosis with an anterior dislocation of her radial head, which was a new finding
      from her previous radiographs. Fourteen months after her initial injury and
      operation, radiographs taken at this visit revealed a radial neck fracture that
      was completely remodeled and had spontaneous relocated and was now aligned with
      the capitellum without any reduction attempt. CONCLUSION: Closed reduction of
      displaced radial neck fractures may be unsuccessful and open reduction may be
      warranted. Excess callus formation post-operatively may have resulted in the
      radial head subluxation; however there was spontaneous reduction with
      conservative treatment without a reduction attempt, most likely related to
      remodeling of the excel callus formation.

PMID- 24027490
TI  - Subungual exotosis of the finger: case report and review of the literature.
AB  - Although common in the toes, subungual exostoses of the fingers are relatively
      rare. We describe the case of a 65-year-old woman who presented with a subungual
      mass of her left long finger. The lesion was excised and pathologic examination
      confirmed the diagnosis of subungual exostosis. We also review the previously
      reported cases of subungual exostoses of the finger. 

PMID- 24027491
TI  - MATCHING IN INFORMAL FINANCIAL INSTITUTIONS.
AB  - This paper analyzes an informal financial institution that brings heterogeneous
      agents together in groups. We analyze decentralized matching into these groups,
      and the equilibrium composition of participants that consequently arises. We find
      that participants sort remarkably well across the competing groups, and that they
      re-sort immediately following an unexpected exogenous regulatory change. These
      findings suggest that the competitive matching model might have applicability and
      bite in other settings where matching is an important equilibrium phenomenon.
      (JEL: O12, O17, G20, D40).

PMID- 24027492
TI  - Quantifying hub-like behavior in protein folding networks.
AB  - The free energy landscape of a protein is a function of many interdependent
      degrees of freedom. For this reason, conceptual constructs (e.g., funnels) have
      been useful to visualize these landscapes. One relatively new construct is the
      idea of a hub-like native state that is the final destination of many non
      interconverting folding pathways. This is in contrast to the idea of a single
      predominant folding pathway connecting the native state to a rapidly
      interconverting ensemble of unfolded states. The key quantity to distinguish
      between these two ideas is the connectivity of the unfolded ensemble. We present
      a metric to determine this connectivity for a given network, which can be
      calculated either from continuous folding trajectories, or a Markov model. The
      metric determines how often a region of space is used as an intermediate on
      transition paths that connect two other regions of space, and we use it here to
      determine how often two parts of the unfolded ensemble are connected directly,
      versus how often these transitions are mediated by the native state.

PMID- 24027493
TI  - Hexavalent Chromate Reductase Activity in Cell Free Extracts of Penicillium sp.
AB  - A chromium-resistant fungus isolated from contaminated air with industrial vapors
      can be used for reducing toxic Cr(VI) to Cr(III). This study analyzes in vitro
      reduction of hexavalent chromium using cell free extract(s) of the fungus that
      was characterized based on optimal temperature, pH, use of electron donors, metal
      ions and initial Cr(VI) concentration in the reaction mixture. This showed the
      highest activity at 37 degrees C and pH 7.0; there is an increase in Cr(VI)
      reductase activity with addition of NADH as an electron donor, and it was highly
      inhibited by Hg(2+), Ca(2+) and Mg(2+), and azide, EDTA, and KCN. 

PMID- 24027494
TI  - Pgrmc1: new roles in the microglial mediation of progesterone-antagonism of
      estradiol-dependent neurite sprouting and in microglial activation.
AB  - Pgrmc1 (progesterone receptor membrane component 1) is a multifunctional 22 kDa
      protein with heme-binding and P450-activating capacity which was recognized under
      different names for roles in cell motility during neural development and in
      cancer, and apoptosis. Pgrmc1 expression in microglia was recently shown by the
      present authors to mediate estrogen-progesterone interactions during axonal
      sprouting and to mediate microglial activation itself. We also discuss other
      functions of Pgramc1 in the nervous system and its possible relationship to the
      18 kDa sigma-2 receptor (S2R). 

PMID- 24027495
TI  - Multiple effects of beta-amyloid on single excitatory synaptic connections in the
      PFC.
AB  - Prefrontal cortex (PFC) is recognized as an AD-vulnerable region responsible for
      defects in cognitive functioning. Pyramidal cell (PC) connections are typically
      facilitating (F) or depressing (D) in PFC. Excitatory post-synaptic potentials
      (EPSPs) were recorded using patch-clamp from single connections in PFC slices of
      rats and ferrets in the presence of beta-amyloid (Abeta). Synaptic transmission
      was significantly enhanced or reduced depending on their intrinsic type
      (facilitating or depressing), Abeta species (Abeta 40 or Abeta 42) and
      concentration (1-200 nM vs. 0.3-1 MU M). Nanomolar Abeta 40 and Abeta 42 had
      opposite effects on F-connections, resulting in fewer or increased EPSP failure
      rates, strengthening or weakening EPSPs and enhancing or inhibiting short-term
      potentiation [STP: synaptic augmentation (SA) and post-tetanic potentiation
      (PTP)], respectively. High Abeta 40 concentrations induced inhibition regardless
      of synaptic type. D-connections were inhibited regardless of Abeta species or
      concentration. The inhibition induced with bath application was hard to recover
      by washout, but a complete recovery was obtained with brief local application and
      prompt washout. Our data suggests that Abeta 40 acts on the prefrontal neuronal
      network by modulating facilitating and depressing synapses. At higher levels,
      both Abeta 40 and Abeta 42 inhibit synaptic activity and cause irreversible
      toxicity once diffusely accumulated in the synaptic environment. 

PMID- 24027496
TI  - MicroRNAs and cell fate in cortical and retinal development.
AB  - MicroRNAs (miRNAs) are involved in crucial steps of neurogenesis, neural
      differentiation, and neuronal plasticity. Here we review experimental evidence
      suggesting that miRNAs may regulate the histogenesis of the cerebral cortex and
      neural retina. Both cortical and retinal early progenitor cells are multipotent,
      that is, they can generate different types of cortical or retinal cells,
      respectively, in one lineage. In both cortical and retinal development, the
      precise timing of activation of cell fate transcription factors results in a
      stereotyped schedule of generation of the different types of neurons. Emerging
      evidence indicates that miRNAs may play an important role in regulating such
      temporal programing of neuronal differentiation. Neuronal subtypes of the cortex
      and retina exhibit distinct miRNA signatures, implying that miRNA codes may be
      used to specify different types of neurons. Interfering with global miRNA
      activity changes the ratio of the different types of neurons produced. In fact,
      there are examples of cell fate genes that are regulated at the translational
      level, both in retinogenesis and in corticogenesis. A model depicting how miRNAs
      might orchestrate both the type and the birth of different neurons is presented
      and discussed. Glossary. * Lineage: the temporally ordered cell progeny of an
      individual progenitor cell. * Specification: the (reversible) process by which a
      cell becomes capable of, and biased toward, a particular fate. * Commitment: the
      process by which cell fate is fully determined and can no longer be affected by
      external cues. * Potency: the entire complement of cells that a progenitor can
      ultimately produce. * Multipotency: the ability to give rise to more than one
      cell type. * Progenitor: a dividing cell that, in contrast to a stem cell, cannot
      proliferate indefinitely. * Antago-miR: modified antisense oligonucleotide that
      blocks the activity of a miRNA. * Heterochronic neuron: type of neurons that is
      generated at inappropriate times of development. * Neuron birth date: the time of
      the last mitosis of a neuronal cell. 

PMID- 24027499
TI  - Elucidating information processing in primate basal ganglia circuitry: a novel
      technique for pathway-selective ablation mediated by immunotoxin.
AB  - Employing a neuron-specific retrograde gene-transfer vector (NeuRet vector), we
      have recently developed a novel technique that achieves pathway-selective
      ablation in the primate brain. This technique is mediated by immunotoxin (IT) and
      eliminates a neuronal population that constitutes a particular pathway, leaving
      other pathways intact. By means of this technique, we have made an attempt to
      remove the hyperdirect pathway selectively from basal ganglia circuitry. The
      hyperdirect pathway links the motor cortex to the subthalamic nucleus (STN)
      directly and plays a crucial role in motor control. After electrical stimulation
      in the motor cortex, triphasic responses consisting of an early excitation, an
      inhibition, and a late excitation are usually elicited in the internal pallidal
      segment (GPi). Several pieces of pharmacophysiological evidence imply that the
      early excitation may be derived from the hyperdirect pathway. In our experiments,
      the NeuRet vector expressing human interleukin-2 receptor alpha-subunit was
      injected into the STN of macaque monkeys. Then, IT injections were performed into
      the supplementary motor area (SMA). When single neuron activity in the GPi was
      recorded in response to the SMA stimulation, it was found that the early
      excitation was significantly reduced with neither the inhibition nor the late
      excitation affected. The spontaneous firing rate and pattern of GPi neurons
      remained to be altered. This clearly indicates that IT-mediated tract targeting
      successfully eliminated the hyperdirect pathway with spontaneous activity of STN
      neurons unaffected. The electrophysiological findings were histologically
      confirmed by retrograde and anterograde neuronal labeling. The overall data
      define that the motor cortically driven early excitation in GPi neurons is
      conveyed through the hyperdirect pathway. The IT-mediated pathway-selective
      ablation technique will provide a powerful tool for elucidating information
      processing in various neural networks.

PMID- 24027497
TI  - alpha4betadelta GABAA receptors and tonic inhibitory current during adolescence:
      effects on mood and synaptic plasticity.
AB  - The onset of puberty is associated with alterations in mood as well as changes in
      cognitive function, which can be more pronounced in females. Puberty onset in
      female mice is associated with increased expression of alpha4betadelta gamma
      amino-butyric acid-A (GABAA) receptors (GABARs) in CA1 hippocampus. These
      receptors, which normally have low expression in this central nervous system
      (CNS) site, emerge along the apical dendrites as well as on the dendritic spines
      of pyramidal neurons, adjacent to excitatory synapses where they underlie a tonic
      inhibition that shunts excitatory current and impairs activation of N-methyl-D
      aspartate (NMDA) receptors, the trigger for synaptic plasticity. As would be
      expected, alpha4betadelta expression at puberty also prevents long-term
      potentiation (LTP), an in vitro model of learning which is a function of network
      activity, induced by theta burst stimulation of the Schaffer collaterals to the
      CA1 hippocampus. The expression of these receptors also impairs spatial learning
      in a hippocampal-dependent task. These impairments are not seen in delta knock
      out (-/-) mice, implicating alpha4betadelta GABARs. alpha4betadelta GABARs are
      also a sensitive target for steroids such as THP ([allo]pregnanolone or 3alpha-OH
      5alpha[beta]-pregnan-20-one), which are dependent upon the polarity of GABAergic
      current. It is well-known that THP can increase depolarizing current gated by
      alpha4betadelta GABARs, but more recent data suggest that THP can reduce
      hyperpolarizing current by accelerating receptor desensitization. At puberty, THP
      reduces the hyperpolarizing GABAergic current, which removes the shunting
      inhibition that impairs synaptic plasticity and learning at this time. However,
      THP, a stress steroid, also increases anxiety, via its action at alpha4betadelta
      GABARs because it is not seen in delta(-/-) mice. These findings will be
      discussed as well as their relevance to changes in mood and cognition at puberty,
      which can be a critical period for certain types of learning and when anxiety
      disorders and mood swings can emerge.

PMID- 24027498
TI  - Role of tonic GABAergic currents during pre- and early postnatal rodent
      development.
AB  - In the last three decades it became evident that the GABAergic system plays an
      essential role for the development of the central nervous system, by influencing
      the proliferation of neuronal precursors, neuronal migration and differentiation,
      as well as by controlling early activity patterns and thus formation of neuronal
      networks. GABA controls neuronal development via depolarizing membrane responses
      upon activation of ionotropic GABA receptors. However, many of these effects
      occur before the onset of synaptic GABAergic activity and thus require the
      presence of extrasynaptic tonic currents in neuronal precursors and immature
      neurons. This review summarizes our current knowledge about the role of tonic
      GABAergic currents during early brain development. In this review we compare the
      temporal sequence of the expression and functional relevance of different GABA
      receptor subunits, GABA synthesizing enzymes and GABA transporters. We also refer
      to other possible endogenous agonists of GABAA receptors. In addition, we
      describe functional consequences mediated by the GABAergic system during early
      developmental periods and discuss current models about the origin of
      extrasynaptic GABA and/or other endogenous GABAergic agonists during early
      developmental states. Finally, we present evidence that tonic GABAergic activity
      is also critically involved in the generation of physiological as well as
      pathophysiological activity patterns before and after the establishment of
      functional GABAergic synaptic connections.

PMID- 24027501
TI  - Different correlation patterns of cholinergic and GABAergic interneurons with
      striatal projection neurons.
AB  - The striatum is populated by a single projection neuron group, the medium spiny
      neurons (MSNs), and several groups of interneurons. Two of the
      electrophysiologically well-characterized striatal interneuron groups are the
      tonically active neurons (TANs), which are presumably cholinergic interneurons,
      and the fast spiking interneurons (FSIs), presumably parvalbumin (PV) expressing
      GABAergic interneurons. To better understand striatal processing it is thus
      crucial to define the functional relationship between MSNs and these interneurons
      in the awake and behaving animal. We used multiple electrodes and standard
      physiological methods to simultaneously record MSN spiking activity and the
      activity of TANs or FSIs from monkeys engaged in a classical conditioning
      paradigm. All three cell populations were highly responsive to the behavioral
      task. However, they displayed different average response profiles and a different
      degree of response synchronization (signal correlation). TANs displayed the most
      transient and synchronized response, MSNs the most diverse and sustained response
      and FSIs were in between on both parameters. We did not find evidence for direct
      monosynaptic connectivity between the MSNs and either the TANs or the FSIs.
      However, while the cross correlation histograms of TAN to MSN pairs were flat,
      those of FSI to MSN displayed positive asymmetrical broad peaks. The FSI-MSN
      correlogram profile implies that the spikes of MSNs follow those of FSIs and both
      are driven by a common, most likely cortical, input. Thus, the two populations of
      striatal interneurons are probably driven by different afferents and play
      complementary functional roles in the physiology of the striatal microcircuit. 

PMID- 24027500
TI  - Congenital hypoplasia of the cerebellum: developmental causes and behavioral
      consequences.
AB  - Over the last 60 years, the spotlight of research has periodically returned to
      the cerebellum as new techniques and insights have emerged. Because of its simple
      homogeneous structure, limited diversity of cell types and characteristic
      behavioral pathologies, the cerebellum is a natural home for studies of cell
      specification, patterning, and neuronal migration. However, recent evidence has
      extended the traditional range of perceived cerebellar function to include
      modulation of cognitive processes and implicated cerebellar hypoplasia and
      Purkinje neuron hypo-cellularity with autistic spectrum disorder. In the light of
      this emerging frontier, we review the key stages and genetic mechanisms behind
      cerebellum development. In particular, we discuss the role of the midbrain
      hindbrain isthmic organizer in the development of the cerebellar vermis and the
      specification and differentiation of Purkinje cells and granule neurons. These
      developmental processes are then considered in relation to recent insights into
      selected human developmental cerebellar defects: Joubert syndrome, Dandy-Walker
      malformation, and pontocerebellar hypoplasia. Finally, we review current research
      that opens up the possibility of using the mouse as a genetic model to study the
      role of the cerebellum in cognitive function. 

PMID- 24027502
TI  - Linking prenatal experience to the emerging musical mind.
AB  - The musical brain is built over time through experience with a multitude of
      sounds in the auditory environment. However, learning the melodies, timbres, and
      rhythms unique to the music and language of one's culture begins already within
      the mother's womb during the third trimester of human development. We review
      evidence that the intrauterine auditory environment plays a key role in shaping
      later auditory development and musical preferences. We describe evidence that
      externally and internally generated sounds influence the developing fetus, and
      argue that such prenatal auditory experience may set the trajectory for the
      development of the musical mind. 

PMID- 24027503
TI  - DISC1 mouse models as a tool to decipher gene-environment interactions in
      psychiatric disorders.
AB  - DISC1 was discovered in a Scottish pedigree in which a chromosomal translocation
      that breaks this gene segregates with psychiatric disorders, mainly depression
      and schizophrenia. Linkage and association studies in diverse populations support
      DISC1 as a susceptibility gene to a variety of neuropsychiatric disorders. Many
      Disc1 mouse models have been generated to study its neuronal functions. These
      mouse models display variable phenotypes, some of them relevant to schizophrenia,
      others to depression. The Disc1 mouse models are popular genetic models for
      studying gene-environment interactions in schizophrenia. Five different Disc1
      models have been combined with environmental factors. The environmental stressors
      employed can be classified as either early immune activation or later social
      paradigms. These studies cover major time points along the neurodevelopmental
      trajectory: prenatal, early postnatal, adolescence, and adulthood. Various
      combinations of molecular, anatomical and behavioral methods have been used to
      assess the outcomes. Additionally, three of the studies sought to rescue the
      resulting abnormalities. Here we provide background on the environmental
      paradigms used, summarize the results of these studies combining Disc1 mouse
      models with environmental stressors and discuss what we can learn and how to
      proceed. A major question is how the genetic and environmental factors determine
      which psychiatric disorder will be clinically manifested. To address this we can
      take advantage of the many Disc1 models available and expose them to the same
      environmental stressor. The complementary experiment would be to expose the same
      model to different environmental stressors. DISC1 is an ideal gene for this
      approach, since in the Scottish pedigree the same chromosomal translocation
      results in different psychiatric conditions. 

PMID- 24027505
TI  - Self-serving episodic memory biases: findings in the repressive coping style.
AB  - Individuals with a repressive coping style self-report low anxiety, but show high
      defensiveness and high physiological arousal. Repressors have impoverished
      negative autobiographical memories and are better able to suppress memory for
      negatively valenced and self-related laboratory materials when asked to do so.
      Research on spontaneous forgetting of negative information in repressors suggests
      that they show significant forgetting of negative items, but only after a delay.
      Unknown is whether increased forgetting after a delay is potentiated by self
      relevance. Here we asked in three experiments whether repressors would show
      reduced episodic memories for negative self-relevant information when tested
      immediately versus after a 2-day delay. We predicted that repressors would show
      an exaggerated reduction in recall of negative self-relevant memories after a
      delay, at least without anew priming of this information. We tested a total of
      300 participants (experiment 1: N = 95, experiment 2: N = 106; experiment 3: N =
      99) of four types: repressors, high-anxious (HA), low-anxious, and defensive HA
      individuals. Participants judged positive and negative adjectives with regard to
      self-descriptiveness, serving as incidental encoding. Surprise free-recall was
      conducted immediately after encoding (experiment 1), after a 2-day delay
      (experiment 2), or after a 2-day delay following priming via a lexical decision
      task (experiment 3). In experiment 1, repressors showed a bias against negative
      self-relevant words in immediate recall. Such a bias was neither observed in
      delayed recall without priming nor in delayed recall with priming. Thus, counter
      to our hypothesis, negative information that was initially judged as self
      relevant was not forgotten at a higher rate after a delay in repressors. We
      suggest that repressors may reinterpret initially negative information in a more
      positive light after a delay, and therefore no longer experience the need to bias
      their recall after a delay. 

PMID- 24027506
TI  - Development of ERN together with an internal model of audio-motor associations.
AB  - The brain's reactions to error are manifested in several event related potentials
      (ERP) components, derived from electroencephalographic (EEG) signals. Although
      these components have been known for decades, their interpretation is still
      controversial. A current hypothesis (first indicator hypothesis) claims that the
      first indication of an action being erroneous leads to a negative deflection of
      the EEG signal over frontal midline areas. In some cases this requires sensory
      feedback in the form of knowledge of results (KR). If KR is given, then the first
      negative deflection can be found around 250 ms after feedback presentation
      (feedback-related negativity, FRN). When KR is not required, a negative
      deflection is found already around 100 ms after action onset (ERN). This
      deflection may be evoked when a mismatch between required and actually executed
      actions is detected. To detect such a mismatch, however, necessitates knowledge
      about which action is required. To test this assumption, the current study
      monitored EEG error components during acquisition of an internal model, i.e.,
      acquisition of the knowledge of which actions are needed to reach certain goals.
      Actions consisted of finger presses on a piano keyboard and goals were tones of a
      certain pitch to be generated, thus the internal model represented audio-motor
      mapping. Results show that with increasing proficiency in mapping goals to
      appropriate actions, the amplitude of the ERN increased, whereas the amplitude of
      the FRN remained unchanged. Thus, when knowledge is present about which action is
      required, this supports generation of an ERN around 100 ms, likely by detecting a
      mismatch between required and performed actions. This is in accordance with the
      first indicator hypothesis. The present study furthermore lends support to the
      notion that FRN mainly relies on comparison of sensory targets with sensory
      feedback. 

PMID- 24027508
TI  - "Back to the future": toward Luria's holistic cultural science of human brain and
      mind in a historical study of mental retardation.

PMID- 24027507
TI  - Plasticity in the sensorimotor cortex induced by Music-supported therapy in
      stroke patients: a TMS study.
AB  - Playing a musical instrument demands the engagement of different neural systems.
      Recent studies about the musician's brain and musical training highlight that
      this activity requires the close interaction between motor and somatosensory
      systems. Moreover, neuroplastic changes have been reported in motor-related areas
      after short and long-term musical training. Because of its capacity to promote
      neuroplastic changes, music has been used in the context of stroke
      neurorehabilitation. The majority of patients suffering from a stroke have motor
      impairments, preventing them to live independently. Thus, there is an increasing
      demand for effective restorative interventions for neurological deficits. Music
      supported Therapy (MST) has been recently developed to restore motor deficits. We
      report data of a selected sample of stroke patients who have been enrolled in a
      MST program (1 month intense music learning). Prior to and after the therapy,
      patients were evaluated with different behavioral motor tests. Transcranial
      Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor
      representations underlying the motor gains observed. Several parameters of
      excitability of the motor cortex were assessed as well as the cortical
      somatotopic representation of a muscle in the affected hand. Our results revealed
      that participants obtained significant motor improvements in the paretic hand and
      those changes were accompanied by changes in the excitability of the motor
      cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke
      patients which may explain its efficacy. 

PMID- 24027509
TI  - The sensory channel of presentation alters subjective ratings and autonomic
      responses toward disgusting stimuli-Blood pressure, heart rate and skin
      conductance in response to visual, auditory, haptic and olfactory presented
      disgusting stimuli.
AB  - Disgust causes specific reaction patterns, observable in mimic responses and body
      reactions. Most research on disgust deals with visual stimuli. However, pictures
      may cause another disgust experience than sounds, odors, or tactile stimuli.
      Therefore, disgust experience evoked by four different sensory channels was
      compared. A total of 119 participants received 3 different disgusting and one
      control stimulus, each presented through the visual, auditory, tactile, and
      olfactory channel. Ratings of evoked disgust as well as responses of the
      autonomic nervous system (heart rate, skin conductance level, systolic blood
      pressure) were recorded and the effect of stimulus labeling and of repeated
      presentation was analyzed. Ratings suggested that disgust could be evoked through
      all senses; they were highest for visual stimuli. However, autonomic reaction
      toward disgusting stimuli differed according to the channel of presentation. In
      contrast to the other, olfactory disgust stimuli provoked a strong decrease of
      systolic blood pressure. Additionally, labeling enhanced disgust ratings and
      autonomic reaction for olfactory and tactile, but not for visual and auditory
      stimuli. Repeated presentation indicated that participant's disgust rating
      diminishes to all but olfactory disgust stimuli. Taken together we argue that the
      sensory channel through which a disgust reaction is evoked matters. 

PMID- 24027504
TI  - Convergence of genetic and environmental factors on parvalbumin-positive
      interneurons in schizophrenia.
AB  - Schizophrenia etiology is thought to involve an interaction between genetic and
      environmental factors during postnatal brain development. However, there is a
      fundamental gap in our understanding of the molecular mechanisms by which
      environmental factors interact with genetic susceptibility to trigger symptom
      onset and disease progression. In this review, we summarize the most recent
      findings implicating oxidative stress as one mechanism by which environmental
      insults, especially early life social stress, impact the development of
      schizophrenia. Based on a review of the literature and the results of our own
      animal model, we suggest that environmental stressors such as social isolation
      render parvalbumin-positive interneurons (PVIs) vulnerable to oxidative stress.
      We previously reported that social isolation stress exacerbates many of the
      schizophrenia-like phenotypes seen in a conditional genetic mouse model in which
      NMDA receptors (NMDARs) are selectively ablated in half of cortical and
      hippocampal interneurons during early postnatal development (Belforte et al.,
      2010). We have since revealed that this social isolation-induced effect is caused
      by impairments in the antioxidant defense capacity in the PVIs in which NMDARs
      are ablated. We propose that this effect is mediated by the down-regulation of
      PGC-1alpha, a master regulator of mitochondrial energy metabolism and anti
      oxidant defense, following the deletion of NMDARs (Jiang et al., 2013). Other
      potential molecular mechanisms underlying redox dysfunction upon gene and
      environmental interaction will be discussed, with a focus on the unique
      properties of PVIs. 

PMID- 24027510
TI  - Don't words come easy? A psychophysical exploration of word superiority.
AB  - Words are made of letters, and yet sometimes it is easier to identify a word than
      a single letter. This word superiority effect (WSE) has been observed when
      written stimuli are presented very briefly or degraded by visual noise. We
      compare performance with letters and words in three experiments, to explore the
      extents and limits of the WSE. Using a carefully controlled list of three letter
      words, we show that a WSE can be revealed in vocal reaction times even to
      undegraded stimuli. With a novel combination of psychophysics and mathematical
      modeling, we further show that the typical WSE is specifically reflected in
      perceptual processing speed: single words are simply processed faster than single
      letters. Intriguingly, when multiple stimuli are presented simultaneously,
      letters are perceived more easily than words, and this is reflected both in
      perceptual processing speed and visual short term memory (VSTM) capacity. So,
      even if single words come easy, there is a limit to the WSE. 

PMID- 24027511
TI  - The impact of sensorimotor experience on affective evaluation of dance.
AB  - Past research demonstrates that we are more likely to positively evaluate a
      stimulus if we have had previous experience with that stimulus. This has been
      shown for judgment of faces, architecture, artworks and body movements. In
      contrast, other evidence suggests that this relationship can also work in the
      inverse direction, at least in the domain of watching dance. Specifically, it has
      been shown that in certain contexts, people derive greater pleasure from watching
      unfamiliar movements they would not be able to physically reproduce compared to
      simpler, familiar actions they could physically reproduce. It remains unknown,
      however, how different kinds of experience with complex actions, such as dance,
      might change observers' affective judgments of these movements. Our aim was to
      clarify the relationship between experience and affective evaluation of whole
      body movements. In a between-subjects design, participants received either
      physical dance training with a video game system, visual and auditory experience
      or auditory experience only. Participants' aesthetic preferences for dance
      stimuli were measured before and after the training sessions. Results show that
      participants from the physical training group not only improved their physical
      performance of the dance sequences, but also reported higher enjoyment and
      interest in the stimuli after training. This suggests that physically learning
      particular movements leads to greater enjoyment while observing them. These
      effects are not simply due to increased familiarity with audio or visual elements
      of the stimuli, as the other two training groups showed no increase in aesthetic
      ratings post-training. We suggest these results support an embodied simulation
      account of aesthetics, and discuss how the present findings contribute to a
      better understanding of the shaping of preferences by sensorimotor experience. 

PMID- 24027512
TI  - Reappraising social emotions: the role of inferior frontal gyrus, temporo
      parietal junction and insula in interpersonal emotion regulation.
AB  - Previous studies have reported the effect of emotion regulation (ER) strategies
      on both individual and social decision-making, however, the effect of regulation
      on socially driven emotions independent of decisions is still unclear. In the
      present study, we investigated the neural effects of using reappraisal to both up
      and down-regulate socially driven emotions. Participants played the Dictator
      Game (DG) in the role of recipient while undergoing fMRI, and concurrently
      applied the strategies of either up-regulation (reappraising the proposer's
      intentions as more negative), down-regulation (reappraising the proposer's
      intentions as less negative), as well as a baseline "look" condition. Results
      showed that regions responding to the implementation of reappraisal (effect of
      strategy, that is, "regulating regions") were the inferior and middle frontal
      gyrus, temporo parietal junction and insula bilaterally. Importantly, the middle
      frontal gyrus activation correlated with the frequency of regulatory strategies
      in daily life, with the insula activation correlating with the perceived ability
      to reappraise the emotions elicited by the social situation. Regions regulated by
      reappraisal (effect of regulation, that is, "regulated regions") were the
      striatum, the posterior cingulate and the insula, showing increased activation
      for the up-regulation and reduced activation for down-regulation, both compared
      to the baseline condition. When analyzing the separate effects of partners'
      behavior, selfish behavior produced an activation of the insula, not observed
      when subjects were treated altruistically. Here we show for the first time that
      interpersonal ER strategies can strongly affect neural responses when
      experiencing socially driven emotions. Clinical implications of these findings
      are also discussed to understand how the way we interpret others' intentions may
      affect the way we emotionally react. 

PMID- 24027513
TI  - What are task-sets: a single, integrated representation or a collection of
      multiple control representations?
AB  - Performing two randomly alternating tasks typically results in higher reaction
      times (RTs) following a task switch, relative to a task repetition. These task
      switch costs (TSC) reflect processes of switching between control settings for
      different tasks. The present study investigated whether task sets operate as a
      single, integrated representation or as an agglomeration of relatively
      independent components. In a cued task switch paradigm, target detection
      (present/absent) and discrimination (blue/green/right-/left-tilted) tasks
      alternated randomly across trials. The target was either a color or an
      orientation singleton among homogeneous distractors. Across two trials, the task
      and target-defining dimension repeated or changed randomly. For task switch
      trials, agglomerated task sets predict a difference between dimension changes and
      repetitions: joint task and dimension switches require full task set
      reconfiguration, while dimension repetitions permit re-using some control
      settings from the previous trial. By contrast, integrated task sets always
      require full switches, predicting dimension repetition effects (DREs) to be
      absent across task switches. RT analyses showed significant DREs across task
      switches as well as repetitions supporting the notion of agglomerated task sets.
      Additionally, two event-related potentials (ERP) were analyzed: the Posterior
      Contralateral-Negativity (PCN) indexing spatial selection dynamics, and the
      Sustained-Posterior-Contralateral-Negativity (SPCN) indexing post-selective
      perceptual/semantic analysis. Significant DREs across task switches were observed
      for both the PCN and SPCN components. Together, DREs across task switches for RTs
      and two functionally distinct ERP components suggest that re-using control
      settings across different tasks is possible. The results thus support the
      "agglomerated-task-set" hypothesis, and are inconsistent with "integrated task
      sets." 

PMID- 24027514
TI  - Extraversion differentiates between model-based and model-free strategies in a
      reinforcement learning task.
AB  - Prominent computational models describe a neural mechanism for learning from
      reward prediction errors, and it has been suggested that variations in this
      mechanism are reflected in personality factors such as trait extraversion.
      However, although trait extraversion has been linked to improved reward learning,
      it is not yet known whether this relationship is selective for the particular
      computational strategy associated with error-driven learning, known as model-free
      reinforcement learning, vs. another strategy, model-based learning, which the
      brain is also known to employ. In the present study we test this relationship by
      examining whether humans' scores on an extraversion scale predict individual
      differences in the balance between model-based and model-free learning strategies
      in a sequentially structured decision task designed to distinguish between them.
      In previous studies with this task, participants have shown a combination of both
      types of learning, but with substantial individual variation in the balance
      between them. In the current study, extraversion predicted worse behavior across
      both sorts of learning. However, the hypothesis that extraverts would be
      selectively better at model-free reinforcement learning held up among a subset of
      the more engaged participants, and overall, higher task engagement was associated
      with a more selective pattern by which extraversion predicted better model-free
      learning. The findings indicate a relationship between a broad personality
      orientation and detailed computational learning mechanisms. Results like those in
      the present study suggest an intriguing and rich relationship between core neuro
      computational mechanisms and broader life orientations and outcomes. 

PMID- 24027515
TI  - The non-stop road from concrete to abstract: high concreteness causes the
      activation of long-range networks.
AB  - Current grounding theories propose that sensory-motor brain systems are not only
      modulated by the comprehension of concrete but also partly of abstract language.
      In order to investigate whether concrete or abstract language elicits similar or
      distinct brain activity, neuronal synchronization patterns were investigated by
      means of long-range EEG coherence analysis. Participants performed a semantic
      judgment task with concrete and abstract sentences. EEG coherence between distant
      electrodes was analyzed in various frequencies before and during sentence
      processing using a bivariate AR-model with time-varying parameters. The theta
      frequency band (3-7 Hz) reflected common and different synchronization networks
      related to working memory processes and memory-related lexico-semantic retrieval
      during processing of both sentence types. In contrast, the beta1 band (13-18 Hz)
      showed prominent differences between both sentence types, whereby concrete
      sentences were associated with higher coherence implicating a more widespread
      range and intensity of mental simulation processes. The gamma band (35-40 Hz)
      reflected the sentences' congruency and indicated the more difficult integration
      of incongruent final nouns into the sentence context. Most importantly, findings
      support the notion that different cognitive operations during sentence processing
      are associated with multiple brain oscillations. 

PMID- 24027516
TI  - The neural correlates of in-group and self-face perception: is there overlap for
      high identifiers?
AB  - Social identity, the part of the self-concept derived from group membership, is a
      key explanatory construct for a wide variety of behaviors, ranging from
      organizational commitment to discrimination toward out-groups. Using functional
      magnetic resonance imaging (fMRI), we examined the neural basis of social
      identity through a comparison with the neural correlates of self-face perception.
      Participants viewed a series of pictures, one at a time, of themselves, a
      familiar other, in-group members, and out-group members. We created a contrast
      for self-face perception by subtracting brain activation in response to the
      familiar other from brain activation in response to the self face, and a contrast
      for social identity by subtracting brain activation in response to out-group
      faces from brain activation in response to in-group faces. In line with previous
      research, for the self-familiar other contrast we found activation in several
      right-hemisphere regions (inferior frontal gyrus, inferior and superior parietal
      lobules). In addition, we found activation in closely-adjacent brain areas for
      the social identity contrast. Importantly, significant clusters of activation in
      this in-group-out-group contrast only emerged to the extent that participants
      reported high identification with the in-group. These results suggest that self
      perception and social identity depend on partly similar neural processes. 

PMID- 24027517
TI  - Modulation of spontaneous alpha brain rhythms using low-intensity transcranial
      direct-current stimulation.
AB  - Transcranial direct-current stimulation (tDCS) is a form of neurostimulation in
      which a constant, low current is delivered directly to the brain area of interest
      by small electrodes. The overall aim of this study was to examine and monitor the
      modulation of brain activity by electroencephalogram (EEG) in the frequency
      domain during tDCS in the resting state. To this end, we considered the
      modulation of spontaneous EEG to be a marker of the perturbation that was induced
      through the direct current (1.5 mA for 15 min). In all conditions (anodal,
      cathodal, and sham), an active electrode was placed over the right posterior
      parietal cortex, and a reference electrode was placed on the ipsilateral deltoid
      muscle. The EEG was recorded using a 64-channel system. The effect of tDCS was
      limited to the alpha rhythm, and the anodal stimulation significantly affected
      the alpha rhythm, whereas the cathodal stimulation did not elicit any
      modifications. Further, we observed modulation of alpha activity in areas that
      were stimulated directly through tDCS and in anterior noncontiguous areas.
      Finally, the anodal effect peaked 7.5 min after stimulation and decreased
      gradually over time. Our study demonstrates that in the resting brain,
      monocephalic anodal tDCS over posterior parietal areas alters ongoing brain
      activity, specifically in the alpha band rhythm. Our data can be used to fine
      tune tDCS protocols in neurorehabilitation settings. 

PMID- 24027518
TI  - Is it a face of a woman or a man? Visual mismatch negativity is sensitive to
      gender category.
AB  - The present study investigated whether gender information for human faces was
      represented by the predictive mechanism indexed by the visual mismatch negativity
      (vMMN) event-related brain potential (ERP). While participants performed a
      continuous size-change-detection task, random sequences of cropped faces were
      presented in the background, in an oddball setting: either various female faces
      were presented infrequently among various male faces, or vice versa. In
      Experiment 1 the inter-stimulus-interval (ISI) was 400 ms, while in Experiment 2
      the ISI was 2250 ms. The ISI difference had only a small effect on the P1
      component, however the subsequent negativity (N1/N170) was larger and more widely
      distributed at longer ISI, showing different aspects of stimulus processing. As
      deviant-minus-standard ERP difference, a parieto-occipital negativity (vMMN)
      emerged in the 200-500 ms latency range (~350 ms peak latency in both
      experiments). We argue that regularity of gender on the photographs is
      automatically registered, and the violation of the gender category is reflected
      by the vMMN. In conclusion the results can be interpreted as evidence for the
      automatic activity of a predictive brain mechanism, in case of an ecologically
      valid category. 

PMID- 24027519
TI  - Looking for the self in pathological unconsciousness.
AB  - There is an intimate relationship between consciousness and the notion of self.
      By studying patients with disorders of consciousness, we are offered with a
      unique lesion approach to tackle the neural correlates of self in the absence of
      subjective reports. Studies employing neuroimaging techniques point to the
      critical involvement of midline anterior and posterior cortices in response to
      the passive presentation of self-referential stimuli, such as the patient's own
      name and own face. Also, resting state studies show that these midline regions
      are severely impaired as a function of the level of consciousness. Theoretical
      frameworks combining all this progress surpass the functional localization of
      self-related cognition and suggest a dynamic system-level approach to the
      phenomenological complexity of subjectivity. Importantly for non-communicating
      patients suffering from disorders of consciousness, the clinical translation of
      these technologies will allow medical professionals and families to better
      comprehend these disorders and plan efficient medical management for these
      patients. 

PMID- 24027520
TI  - Cortical midline structures and autobiographical-self processes: an activation
      likelihood estimation meta-analysis.
AB  - The autobiographical-self refers to a mental state derived from the retrieval and
      assembly of memories regarding one's biography. The process of retrieval and
      assembly, which can focus on biographical facts or personality traits or some
      combination thereof, is likely to vary according to the domain chosen for an
      experiment. To date, the investigation of the neural basis of this process has
      largely focused on the domain of personality traits using paradigms that
      contrasted the evaluation of one's traits (self-traits) with those of another
      person's (other-traits). This has led to the suggestion that cortical midline
      structures (CMSs) are specifically related to self states. Here, with the goal of
      testing this suggestion, we conducted activation-likelihood estimation (ALE) meta
      analyses based on data from 28 neuroimaging studies. The ALE results show that
      both self-traits and other-traits engage CMSs; however, the engagement of medial
      prefrontal cortex is greater for self-traits than for other-traits, while the
      posteromedial cortex is more engaged for other-traits than for self-traits. These
      findings suggest that the involvement CMSs is not specific to the evaluation of
      one's own traits, but also occurs during the evaluation of another person's
      traits. 

PMID- 24027523
TI  - Inferring trial-to-trial excitatory and inhibitory synaptic inputs from membrane
      potential using Gaussian mixture Kalman filtering.
AB  - Time-varying excitatory and inhibitory synaptic inputs govern activity of neurons
      and process information in the brain. The importance of trial-to-trial
      fluctuations of synaptic inputs has recently been investigated in neuroscience.
      Such fluctuations are ignored in the most conventional techniques because they
      are removed when trials are averaged during linear regression techniques. Here,
      we propose a novel recursive algorithm based on Gaussian mixture Kalman filtering
      (GMKF) for estimating time-varying excitatory and inhibitory synaptic inputs from
      single trials of noisy membrane potential in current clamp recordings. The KF is
      followed by an expectation maximization (EM) algorithm to infer the statistical
      parameters (time-varying mean and variance) of the synaptic inputs in a non
      parametric manner. As our proposed algorithm is repeated recursively, the
      inferred parameters of the mixtures are used to initiate the next iteration.
      Unlike other recent algorithms, our algorithm does not assume an a priori
      distribution from which the synaptic inputs are generated. Instead, the algorithm
      recursively estimates such a distribution by fitting a Gaussian mixture model
      (GMM). The performance of the proposed algorithms is compared to a previously
      proposed PF-based algorithm (Paninski et al., 2012) with several illustrative
      examples, assuming that the distribution of synaptic input is unknown. If noise
      is small, the performance of our algorithms is similar to that of the previous
      one. However, if noise is large, they can significantly outperform the previous
      proposal. These promising results suggest that our algorithm is a robust and
      efficient technique for estimating time varying excitatory and inhibitory
      synaptic conductances from single trials of membrane potential recordings. 

PMID- 24027522
TI  - Memory for hand-use depends on consistency of handedness.
AB  - Individuals who do not consistently use the same hand to perform unimanual tasks
      (inconsistent-handed) outperform consistent right- and left-handed individuals on
      tests of episodic memory. We explored whether the inconsistent-hander (ICH)
      memory advantage extends to memory for unimanual hand use itself. Are ICHs better
      able to remember which hand they used to perform actions? Opposing predictions
      are possible, stemming from the finding that some regions of the corpus callosum
      are larger in ICHs, especially those that connect motor areas. One hypothesis is
      that greater callosally mediated interhemispheric interaction produces ICHs'
      superior retrieval of episodic memories, and this may extend to episodic memories
      for hand use. Alternatively, we also hypothesized that greater interhemispheric
      interaction could produce more bilateral activation in motor areas during the
      performance and retrieval of unimanual actions. This could interfere with ICHs'
      ability to remember which hand they used. To test these competing predictions in
      the current study, consistent- and inconsistent-handers performed unimanual
      actions, half of which required manipulating objects and half of which did not.
      Each action was performed four times in one of five conditions that differed in
      the ratio of left to right hand use: always left (4:0), usually left (3:1), equal
      (2:2), usually right (1:3), or always right (0:4). We compared consistent- and
      inconsistent-handers on recall of the left:right ratio for each action. ICHs
      remembered how they performed actions better than consistent-handers, regardless
      of ratio. These findings provide another example of superior episodic retrieval
      in ICHs. We discuss how greater interaction might benefit memory for hand use. 

PMID- 24027521
TI  - How relevant is social interaction in second language learning?
AB  - Verbal language is the most widespread mode of human communication, and an
      intrinsically social activity. This claim is strengthened by evidence emerging
      from different fields, which clearly indicates that social interaction influences
      human communication, and more specifically, language learning. Indeed, research
      conducted with infants and children shows that interaction with a caregiver is
      necessary to acquire language. Further evidence on the influence of sociality on
      language comes from social and linguistic pathologies, in which deficits in
      social and linguistic abilities are tightly intertwined, as is the case for
      Autism, for example. However, studies on adult second language (L2) learning have
      been mostly focused on individualistic approaches, partly because of
      methodological constraints, especially of imaging methods. The question as to
      whether social interaction should be considered as a critical factor impacting
      upon adult language learning still remains underspecified. Here, we review
      evidence in support of the view that sociality plays a significant role in
      communication and language learning, in an attempt to emphasize factors that
      could facilitate this process in adult language learning. We suggest that
      sociality should be considered as a potentially influential factor in adult
      language learning and that future studies in this domain should explicitly target
      this factor. 

PMID- 24027524
TI  - Robustness of muscle synergies during visuomotor adaptation.
AB  - During visuomotor adaptation a novel mapping between visual targets and motor
      commands is gradually acquired. How muscle activation patterns are affected by
      this process is an open question. We tested whether the structure of muscle
      synergies is preserved during adaptation to a visuomotor rotation. Eight subjects
      applied targeted isometric forces on a handle instrumented with a force
      transducer while electromyographic (EMG) activity was recorded from 13 shoulder
      and elbow muscles. The recorded forces were mapped into horizontal displacements
      of a virtual sphere with simulated mass, elasticity, and damping. The task
      consisted of moving the sphere to a target at one of eight equally spaced
      directions. Subjects performed three baseline blocks of 32 trials, followed by
      six blocks with a 45 degrees  CW rotation applied to the planar force, and
      finally three wash-out blocks without the perturbation. The sphere position at
      100 ms after movement onset revealed significant directional error at the
      beginning of the rotation, a gradual learning in subsequent blocks, and
      aftereffects at the beginning of the wash-out. The change in initial force
      direction was closely related to the change in directional tuning of the initial
      EMG activity of most muscles. Throughout the experiment muscle synergies
      extracted using a non-negative matrix factorization algorithm from the muscle
      patterns recorded during the baseline blocks could reconstruct the muscle
      patterns of all other blocks with an accuracy significantly higher than chance
      indicating structural robustness. In addition, the synergies extracted from
      individual blocks remained similar to the baseline synergies throughout the
      experiment. Thus synergy structure is robust during visuomotor adaptation
      suggesting that changes in muscle patterns are obtained by rotating the
      directional tuning of the synergy recruitment. 

PMID- 24027525
TI  - Comparing the effect of humanoid and human face for the spatial orientation of
      attention.
AB  - The current study was designed to investigate how the automatic spatial
      orientation of attention induced by the perception of another agent's orientation
      of attention is modulated by the social nature of the other agent. Modified
      versions of the Posner task, using a real or schematic face with eyes or head
      looking toward the left or the right before a to-be-detected target appears on
      one side of the screen have been used to demonstrate a reduction of reaction time
      (RT) for target detection when the gaze is directed toward the target, even
      though the cue is not informative. We compared the effect of two agents, the
      humanoid robotic platform Nao and a real human, using head turn to cue the
      spatial orientation of attention. Our results reproduced the typical Posner
      effect, with reduced RT to valid compared to invalid spatial cues. RT increased
      when no spatial information was provided, interpreted as an increased difficulty
      to disengage from a direct gaze. RT was also increased when the robot was used
      instead of the human face and when the eyes of the stimuli were blacked out. Both
      effects were interpreted as resulting from an increased difficulty to disengage
      attention from the central stimulus because of its novelty. In all experiments,
      there was no interaction between cue validity and cue agent, implying that the
      exact nature of the human-like agent didn't have an effect on the automatic
      spatial orientation of attention. Altogether, our results imply that a humanoid
      face is as potent as a human face to trigger an automatic orientation of spatial
      attention. 

PMID- 24027526
TI  - The effects of the histone deacetylase inhibitor 4-phenylbutyrate on gap junction
      conductance and permeability.
AB  - Longitudinal resistance is a key factor in determining cardiac action potential
      propagation. Action potential conduction velocity has been shown to be
      proportional to the square root of longitudinal resistance. A major determinant
      of longitudinal resistance in myocardium is the gap junction channel, comprised
      connexin proteins. Within the ventricular myocardium connexin43 (Cx43) is the
      dominantly expressed connexin. Reduced numbers of gap junction channels will
      result in an increase in longitudinal resistance creating the possibility of
      slowed conduction velocity while increased numbers of channels would potentially
      result in an increase in conduction velocity. We sought to determine if
      inhibition of histone deacetylase (HDAC) by 4-phenylbutyrate (4-PB), a known
      inhibitor of HDAC resulted in an increase in junctional conductance and
      permeability, which is not the result of changes in single channel unitary
      conductance. These experiments were performed using HEK-293 cells and HeLa cells
      stably transfected with Cx43. Following treatment with increasing concentrations
      of 4-PB up-regulation of Cx43 was observed via Western blot analysis. Junctional
      (g j) conductance and unitary single channel conductance were measured via whole
      cell patch clamp. In addition intercellular transfer of lucifer yellow (LY) was
      determined by fluorescence microscopy. The data in this study indicate that 4-PB
      is able to enhance functional Cx43 gap junction coupling as indicated by LY dye
      transfer and multichannel and single channel data along with Western blot
      analysis. As a corollary, pharmacological agents such as 4-PB have the potential,
      by increasing intercellular coupling, to reduce the effect of ischemia. It
      remains to be seen whether drugs like 4-PB will be effective in preventing
      cardiac maladies. 

PMID- 24027527
TI  - Bridging the gap between computation and clinical biology: validation of cable
      theory in humans.
AB  - INTRODUCTION: Computerized simulations of cardiac activity have significantly
      contributed to our understanding of cardiac electrophysiology, but techniques of
      simulations based on patient-acquired data remain in their infancy. We sought to
      integrate data acquired from human electrophysiological studies into patient
      specific models, and validated this approach by testing whether
      electrophysiological responses to sequential premature stimuli could be predicted
      in a quantitatively accurate manner. METHODS: Eleven patients with structurally
      normal hearts underwent electrophysiological studies. Semi-automated analysis was
      used to reconstruct activation and repolarization dynamics for each electrode.
      This S 2 extrastimuli data was used to inform individualized models of cardiac
      conduction, including a novel derivation of conduction velocity restitution.
      Activation dynamics of multiple premature extrastimuli were then predicted from
      this model and compared against measured patient data as well as data derived
      from the ten-Tusscher cell-ionic model. RESULTS: Activation dynamics following a
      premature S 3 were significantly different from those after an S 2. Patient
      specific models demonstrated accurate prediction of the S 3 activation wave,
      (Pearson's R (2) = 0.90, median error 4%). Examination of the modeled conduction
      dynamics allowed inferences into the spatial dispersion of activation delay.
      Further validation was performed against data from the ten-Tusscher cell-ionic
      model, with our model accurately recapitulating predictions of repolarization
      times (R (2) = 0.99). CONCLUSIONS: Simulations based on clinically acquired data
      can be used to successfully predict complex activation patterns following
      sequential extrastimuli. Such modeling techniques may be useful as a method of
      incorporation of clinical data into predictive models.

PMID- 24027529
TI  - Non-linear dynamics of human locomotion: effects of rhythmic auditory cueing on
      local dynamic stability.
AB  - It has been observed that times series of gait parameters [stride length (SL),
      stride time (ST), and stride speed (SS)], exhibit long-term persistence and
      fractal-like properties. Synchronizing steps with rhythmic auditory stimuli
      modifies the persistent fluctuation pattern to anti-persistence. Another non
      linear method estimates the degree of resilience of gait control to small
      perturbations, i.e., the local dynamic stability (LDS). The method makes use of
      the maximal Lyapunov exponent, which estimates how fast a non-linear system
      embedded in a reconstructed state space (attractor) diverges after an
      infinitesimal perturbation. We propose to use an instrumented treadmill to
      simultaneously measure basic gait parameters (time series of SL, ST, and SS from
      which the statistical persistence among consecutive strides can be assessed), and
      the trajectory of the center of pressure (from which the LDS can be estimated).
      In 20 healthy participants, the response to rhythmic auditory cueing (RAC) of LDS
      and of statistical persistence [assessed with detrended fluctuation analysis
      (DFA)] was compared. By analyzing the divergence curves, we observed that long
      term LDS (computed as the reverse of the average logarithmic rate of divergence
      between the 4th and the 10th strides downstream from nearest neighbors in the
      reconstructed attractor) was strongly enhanced (relative change +73%). That is
      likely the indication of a more dampened dynamics. The change in short-term LDS
      (divergence over one step) was smaller (+3%). DFA results (scaling exponents)
      confirmed an anti-persistent pattern in ST, SL, and SS. Long-term LDS (but not
      short-term LDS) and scaling exponents exhibited a significant correlation between
      them (r = 0.7). Both phenomena probably result from the more conscious/voluntary
      gait control that is required by RAC. We suggest that LDS and statistical
      persistence should be used to evaluate the efficiency of cueing therapy in
      patients with neurological gait disorders. 

PMID- 24027530
TI  - Appearance of differentiated cells derived from polar body nuclei in the
      silkworm, Bombyx mori.
AB  - In Bombyx mori, polar body nuclei are observed until 9 h after egg lying,
      however, the fate of polar body nuclei remains unclear. To examine the fate of
      polar body nuclei, we employed a mutation of serosal cell pigmentation, pink-eyed
      white egg (pe). The heterozygous pe/+ (pe) females produced black serosal cells
      in white eggs, while pe/pe females did not produce black serosal cells in white
      eggs. These results suggest that the appearance of black serosal cells in white
      eggs depends on the genotype (pe/+ (pe) ) of the mother. Because the polar body
      nuclei had + (pe) genes in the white eggs laid by a pe/+ (pe) female, polar body
      nuclei participate in development and differentiate into functional cell (serosal
      cells). Analyses of serosal cells pigmentation indicated that ~30% of the eggs
      contained polar-body-nucleus-derived cells. These results demonstrate that polar
      body-nucleus-derived cells appeared at a high frequency under natural conditions.
      Approximately 80% of polar-body-nucleus-derived cells appeared near the anterior
      pole and the dorsal side, which is opposite to where embryogenesis occurs. The
      number of cells derived from the polar body nuclei was very low. Approximately
      26% of these eggs contained only one black serosal cell. PCR-based analysis
      revealed that the polar-body-nucleus-derived cells disappeared in late embryonic
      stages (stage 25). Overall, polar-body-nuclei-derived cells were unlikely to
      contribute to embryos. 

PMID- 24027528
TI  - Intracellular ion channels and cancer.
AB  - Several types of channels play a role in the maintenance of ion homeostasis in
      subcellular organelles including endoplasmatic reticulum, nucleus, lysosome,
      endosome, and mitochondria. Here we give a brief overview of the contribution of
      various mitochondrial and other organellar channels to cancer cell proliferation
      or death. Much attention is focused on channels involved in intracellular calcium
      signaling and on ion fluxes in the ATP-producing organelle mitochondria.
      Mitochondrial K(+) channels (Ca(2+)-dependent BKCa and IKCa, ATP-dependent KATP,
      Kv1.3, two-pore TWIK-related Acid-Sensitive K(+) channel-3 (TASK-3)), Ca(2+)
      uniporter MCU, Mg(2+)-permeable Mrs2, anion channels (voltage-dependent chloride
      channel VDAC, intracellular chloride channel CLIC) and the Permeability
      Transition Pore (MPTP) contribute importantly to the regulation of function in
      this organelle. Since mitochondria play a central role in apoptosis, modulation
      of their ion channels by pharmacological means may lead to death of cancer cells.
      The nuclear potassium channel Kv10.1 and the nuclear chloride channel CLIC4 as
      well as the endoplasmatic reticulum (ER)-located inositol 1,4,5-trisphosphate
      (IP3) receptor, the ER-located Ca(2+) depletion sensor STIM1 (stromal interaction
      molecule 1), a component of the store-operated Ca(2+) channel and the ER-resident
      TRPM8 are also mentioned. Furthermore, pharmacological tools affecting organellar
      channels and modulating cancer cell survival are discussed. The channels
      described in this review are summarized on Figure 1. Overall, the view is
      emerging that intracellular ion channels may represent a promising target for
      cancer treatment. 

PMID- 24027531
TI  - Endoplasmic reticulum stress in human skeletal muscle: any contribution to
      sarcopenia?
AB  - Skeletal muscle is vital to life as it provides the mechanical power for
      locomotion, posture and breathing. Beyond these vital functions, skeletal muscle
      also plays an essential role in the regulation of whole body metabolism, e.g.,
      glucose homeostasis. Although progressive loss of muscle mass with age seems
      unavoidable, it is critical for older people to keep the highest mass as
      possible. It is clear that the origin of sarcopenia is multifactorial but, in the
      present review, it was deliberately chosen to evaluate the likely contribution of
      one specific cellular stress, namely the endoplasmic reticulum (ER) stress. It is
      proposed that ER stress can: (1) directly impact muscle mass as one fate of
      prolonged and unresolved ER stress is cell death and; (2) indirectly create a
      state of anabolic resistance by inhibiting the mammalian target of rapamycin
      complex 1 (mTORC1) pathway. With age, many of the key components of the unfolded
      protein response, such as the chaperones and enzymes, display reduced expression
      and activity resulting in a dysfunctional ER, accelerating the rate of proteins
      discarded via the ER-associated degradation. In addition, ER stress can block the
      mTORC1 pathway which is essential in the response to the anabolic stimulus of
      nutrients and contractile activity thereby participating to the well-known
      anabolic resistance state in skeletal muscle during ageing. As exercise increases
      the expression of several chaperones, it could anticipate or restore the loss of
      unfolded protein response components with age and thereby reduce the level of ER
      stress. This hypothesis has not been tested yet but it could be a new mechanism
      behind the beneficial effects of exercise in the elderly not only for the
      preservation of muscle mass but also for the regulation of whole body metabolism.

PMID- 24027532
TI  - The evolution of genome-scale models of cancer metabolism.
AB  - The importance of metabolism in cancer is becoming increasingly apparent with the
      identification of metabolic enzyme mutations and the growing awareness of the
      influence of metabolism on signaling, epigenetic markers, and transcription.
      However, the complexity of these processes has challenged our ability to make
      sense of the metabolic changes in cancer. Fortunately, constraint-based modeling,
      a systems biology approach, now enables one to study the entirety of cancer
      metabolism and simulate basic phenotypes. With the newness of this field, there
      has been a rapid evolution of both the scope of these models and their
      applications. Here we review the various constraint-based models built for cancer
      metabolism and how their predictions are shedding new light on basic cancer
      phenotypes, elucidating pathway differences between tumors, and dicovering
      putative anti-cancer targets. As the field continues to evolve, the scope of
      these genome-scale cancer models must expand beyond central metabolism to address
      questions related to the diverse processes contributing to tumor development and
      metastasis. 

PMID- 24027533
TI  - Improving cardiac myocytes performance by carbon nanotubes platforms.
AB  - The application of nanotechnology to the cardiovascular system has increasingly
      caught scientists' attention as a potentially powerful tool for the development
      of new generation devices able to interface, repair, or boost the performance of
      cardiac tissue. Carbon nanotubes (CNTs) are considered as promising materials for
      nanomedicine applications in general and have been recently tested toward
      excitable cell growth. CNTs are cylindrically shaped structures made up of rolled
      up graphene sheets, with unique electrical, thermal, and mechanical properties,
      able to effectively conducting electrical current in electrochemical interfaces.
      CNTs-based scaffolds have been recently found to support the in vitro growth of
      cardiac cells: in particular, their ability to improve cardiomyocytes
      proliferation, maturation, and electrical behavior are making CNTs extremely
      attractive for the development and exploitation of interfaces able to impact on
      cardiac cells physiology and function. 

PMID- 24027534
TI  - Physiology and pharmacology of the cardiovascular adrenergic system.
AB  - Heart failure (HF), the leading cause of death in the western world, ensues in
      response to cardiac injury or insult and represents the inability of the heart to
      adequately pump blood and maintain tissue perfusion. It is characterized by
      complex interactions of several neurohormonal mechanisms that get activated in
      the syndrome in order to try and sustain cardiac output in the face of
      decompensating function. The most prominent among these neurohormonal mechanisms
      is the adrenergic (or sympathetic) nervous system (ANS), whose activity and
      outflow are greatly elevated in HF. Acutely, provided that the heart still works
      properly, this activation of the ANS will promptly restore cardiac function
      according to the fundamental Frank-Starling law of cardiac function. However, if
      the cardiac insult persists over time, this law no longer applies and ANS will
      not be able to sustain cardiac function. This is called decompensated HF, and the
      hyperactive ANS will continue to "push" the heart to work at a level much higher
      than the cardiac muscle can handle. From that point on, ANS hyperactivity becomes
      a major problem in HF, conferring significant toxicity to the failing heart and
      markedly increasing its morbidity and mortality. The present review discusses the
      role of the ANS in cardiac physiology and in HF pathophysiology, the mechanisms
      of regulation of ANS activity and how they go awry in chronic HF, and, finally,
      the molecular alterations in heart physiology that occur in HF along with their
      pharmacological and therapeutic implications for the failing heart. 

PMID- 24027535
TI  - PEX16: a multifaceted regulator of peroxisome biogenesis.
AB  - PEROXISOMES ARE FORMED BY TWO DISTINCT PATHWAYS: the growth and fission of mature
      peroxisomes and de novo synthesis at the endoplasmic reticulum (ER). While many
      of the molecular mechanisms underlying these two pathways remain to be
      elucidated, it is generally accepted that their relative contribution to
      peroxisome formation may vary depending on the species, cell type and/or
      physiological status of the organism. One pertinent example of the apparent
      differences in the regulation of peroxisome biogenesis among evolutionarily
      diverse species is the involvement of the peroxin PEX16. In Yarrowia lipolytica,
      for instance, PEX16 is an intraperoxisomal peripheral membrane protein that
      participates in peroxisomal fission. By contrast, Human PEX16 is an integral
      membrane protein that is thought to function at the ER during the early stages of
      de novo peroxisome formation and also recruits peroxisomal membrane proteins
      directly to mature peroxisomes. Similarly, PEX16 in the plant Arabidopsis
      thaliana is speculated to be a PMP receptor at the ER and peroxisomes, and is
      also required for the formation of other ER-derived organelles, such as oil and
      protein bodies. Here we briefly review the current knowledge of Y. lipolytica,
      human and A. thaliana PEX16 in the context of our overall understanding of
      peroxisome biogenesis and the role of the ER in this process in these three
      divergent species.

PMID- 24027537
TI  - Peak exercise capacity prediction from a submaximal exercise test in coronary
      artery disease patients.
AB  - The purpose of this study was to determine whether a rating of perceived exertion
      scale (RPE) obtained during submaximal exercise could be used to predict peak
      exercise capacity (METpeak) in coronary artery disease (CAD) patients.
      Angiographically documented CAD patients (n = 124, 87% on beta blockade)
      completed a symptom-limited peak exercise test on a bicycle ergometer, reporting
      RPE values at every second load on a scale of 6-20. Regression analysis was used
      to develop equations for predicting METpeak. We found that submaximal METs at a
      workload of 60/75 W (for women and men, respectively) and the corresponding RPE
      (METs/RPE ratio) was the most powerful predictor of METpeak (r = 0.67, p <
      0.0001). The final model included the submaximal METs/RPE ratio, body mass index
      (BMI), sex, resting heart rate, smoking history, age, and use of a beta blockade
      (r = 0.86, p < 0.0001, SEE 0.98 METs). These data suggest that RPE at submaximal
      exercise intensity is related to METpeak in CAD patients. The model based on
      easily measured variables at rest and during "warm-up" exercise can reasonably
      predict absolute METpeak in patients with CAD. 

PMID- 24027538
TI  - Risky Decision-Making but Not Delay Discounting Improves during Inpatient
      Treatment of Polysubstance Dependent Alcoholics.
AB  - BACKGROUND: High levels of impulsivity, characteristics of addicted patients, are
      known to be important predictors of relapse. However, so far, little is known
      about the stability or variability of two main components of impulsivity (delay
      discounting and decision-making). The present study examined the changes in
      impulsivity during the first week of an abstinence based, behavioral orientated
      inpatient treatment program. METHOD: Thirty-seven polysubstance dependent
      alcoholics completed the Delay Discounting Task (DDT), and the Iowa Gambling Task
      (IGT) using the original version with decks A'B'C'D', and an alternative version
      with decks K'L'M'N', for measuring decision-making, after 2 and 6 weeks of active
      treatment. RESULTS: It was found that performances on the IGT changed during
      treatment while performances on the DDT did not (test-retest period: 4 weeks).
      CONCLUSION: The results provide preliminary evidence that improvements in
      decision-making might be related to treatment effects. All patients followed a
      highly structured cognitive-behavioral treatment program, which might have
      enhanced their executive functioning (coping skills training).

PMID- 24027539
TI  - An Investigation of Factors Increasing the Risk of Aggressive Behavior among
      Schizophrenic Inpatients.
AB  - AIM OF THE STUDY: This study tried to identify risk factors of aggressive
      behavior in a population of schizophrenic inpatients. We tested the association
      between aggressive behavior and socio-demographic characteristics, addictive
      disorders, history of suicide attempt, and sexual violence, impulsivity, and
      sensation seeking. METHODS: All consecutive schizophrenic inpatients (100) were
      assessed during 6 months. Aggressive behavior was quantified with a standardized
      scale, the Overt Aggression Scale (OAS). We studied socio-demographic
      characteristics and the history of suicide attempt and sexual violence with a
      specific standardized questionnaire. Addictive disorders were identified with the
      Fagerstrom and CAGE questionnaires and with the DSM-IV-R diagnostic criteria for
      nicotine, alcohol, cannabis opiates, and cocaine abuse and dependence disorders.
      Lastly, we studied sensation seeking with the Zuckerman scale and impulsivity
      with the Barratt scale. RESULTS: Linear regression identified four factors
      associated with aggressive behavior: male gender (odd ratio = 12.8), history of
      sexual violence (odd ratio = 3.6), Fagerstrom score (odd ratio = 1.3), number of
      cigarettes smoked each day (odd ratio = 1.16). Patients with nicotine use or
      dependence had significantly higher levels of OAS scores. This difference was not
      observed between patients with or without alcohol dependence. OAS scores were
      correlated to the number of cigarettes smoked each day and to Fagerstrom scores.
      Patients with a higher level of sensation seeking and impulsivity also had higher
      OAS scores. CONCLUSION: A typical schizophrenic patient at risk of showing
      aggressive behavior is a man, who smokes and presents a history of sexual
      violence.

PMID- 24027540
TI  - Persistent consequences of atypical early number concepts.
AB  - How does symbolic number knowledge performance help identify young children at
      risk for poor mathematics achievement outcomes? In research and practice,
      classification of mathematics learning disability (MLD, or dyscalculia) is
      typically based on composite scores from broad measures of mathematics
      achievement. These scores do predict later math achievement levels, but do not
      specify the nature of math difficulties likely to emerge among students at
      greatest risk for long-term mathematics failure. Here we report that gaps in 2nd
      and 3rd graders' number knowledge predict specific types of errors made on math
      assessments at Grade 8. Specifically, we show that early whole number
      misconceptions predict slower and less accurate performance, and atypical
      computational errors, on Grade 8 arithmetic tests. We demonstrate that basic
      number misconceptions can be detected by idiosyncratic responses to number
      knowledge items, and that when such misconceptions are evident during primary
      school they persist throughout the school age years, with variable manifestation
      throughout development. We conclude that including specific qualitative
      assessments of symbolic number knowledge in primary school may provide greater
      specificity of the types of difficulties likely to emerge among students at risk
      for poor mathematics outcomes. 

PMID- 24027541
TI  - Impact of civil war on emotion recognition: the denial of sadness in Sierra
      Leone.
AB  - Studies of children with atypical emotional experience demonstrate that childhood
      exposure to high levels of hostility and threat biases emotion perception. This
      study investigates emotion processing, in former child soldiers and non-combatant
      civilians. All participants have experienced prolonged violence exposure during
      childhood. The study, carried out in Sierra Leone, aimed to examine the effects
      of exposure to and forced participation in acts of extreme violence on the
      emotion processing of young adults war survivors. A total of 76 young, male
      adults (38 former child soldier survivors and 38 civilian survivors) were tested
      in order to assess participants' ability to identify four different facial
      emotion expressions from photographs and movies. Both groups were able to
      recognize facial expressions of emotion. However, despite their general ability
      to correctly identify facial emotions, participants showed a significant response
      bias in their recognition of sadness. Both former soldiers and civilians made
      more errors in identifying expressions of sadness than in the other three
      emotions and when mislabeling sadness participants most often described it as
      anger. Conversely, when making erroneous identifications of other emotions,
      participants were most likely to label the expressed emotion as sadness. In
      addition, while for three of the four emotions participants were better able to
      make a correct identification the greater the intensity of the expression, this
      pattern was not observed for sadness. During movies presentation the recognition
      of sadness was significantly worse for soldiers. While both former child soldiers
      and civilians were found to be able to identify facial emotions, a significant
      response bias in their attribution of negative emotions was observed. Such bias
      was particularly pronounced in former child soldiers. These findings point to a
      pervasive long-lasting effect of childhood exposure to violence on emotion
      processing in later life. 

PMID- 24027542
TI  - Dispatching the wandering mind? Toward a laboratory method for cuing
      "spontaneous" off-task thought.
AB  - Cognitive psychologists and neuroscientists study most phenomena of attention by
      measuring subjects' overt responses to discrete environmental stimuli that can be
      manipulated to test competing theories. The mind wandering experience, however,
      cannot be locally instigated by cleverly engineered stimuli. Investigators must
      therefore rely on correlational and observational methods to understand subjects'
      flow of thought, which is only occasionally and indirectly monitored. In an
      effort toward changing this state of affairs, we present four experiments that
      develop a method for inducing mind wandering episodes-on demand-in response to
      task-embedded cues. In an initial laboratory session, subjects described their
      personal goals and concerns across several life domains (amid some filler
      questionnaires). In a second session, 48 h later, subjects completed a go/no-go
      task in which they responded to the perceptual features of words; unbeknownst to
      subjects, some stimulus words were presented in triplets to represent the
      personal concerns they had described in session 1. Thought probes appearing
      shortly after these personal-goal triplets indicated that, compared to control
      triplets, priming subjects' concerns increased mind wandering rate by about 3-4%.
      We argue that this small effect is, nonetheless, a promising development toward
      the pursuit of an experimentally informed, theory-driven science of mind
      wandering. 

PMID- 24027536
TI  - Interaction of aldehydes derived from lipid peroxidation and membrane proteins.
AB  - A great variety of compounds are formed during lipid peroxidation of
      polyunsaturated fatty acids of membrane phospholipids. Among them, bioactive
      aldehydes, such as 4-hydroxyalkenals, malondialdehyde (MDA) and acrolein, have
      received particular attention since they have been considered as toxic messengers
      that can propagate and amplify oxidative injury. In the 4-hydroxyalkenal class, 4
      hydroxy-2-nonenal (HNE) is the most intensively studied aldehyde, in relation not
      only to its toxic function, but also to its physiological role. Indeed, HNE can
      be found at low concentrations in human tissues and plasma and participates in
      the control of biological processes, such as signal transduction, cell
      proliferation, and differentiation. Moreover, at low doses, HNE exerts an anti
      cancer effect, by inhibiting cell proliferation, angiogenesis, cell adhesion and
      by inducing differentiation and/or apoptosis in various tumor cell lines. It is
      very likely that a substantial fraction of the effects observed in cellular
      responses, induced by HNE and related aldehydes, be mediated by their interaction
      with proteins, resulting in the formation of covalent adducts or in the
      modulation of their expression and/or activity. In this review we focus on
      membrane proteins affected by lipid peroxidation-derived aldehydes, under
      physiological and pathological conditions. 

PMID- 24027543
TI  - The wild ways of conscious will: what we do, how we do it, and why it has
      meaning.
AB  - It is becoming increasingly mainstream to claim that conscious will is an
      illusion. This assertion is based on a host of findings that indicate conscious
      will does not share an efficient-cause relationship with actions. As an
      alternative, the present paper will propose that conscious will is not about
      causing actions, but rather, about constraining action systems toward producing
      outcomes. In addition, it will be proposed that we generate and sustain multiple
      outcomes simultaneously because the multi-scale dynamics by which we do so are,
      themselves, self-sustaining. Finally, it will be proposed that self-sustaining
      dynamics entail meaning (i.e., conscious content) because they naturally and
      necessarily constitute embodiments of context. 

PMID- 24027544
TI  - Susceptibility to a multisensory speech illusion in older persons is driven by
      perceptual processes.
AB  - Recent studies suggest that multisensory integration is enhanced in older adults
      but it is not known whether this enhancement is solely driven by perceptual
      processes or affected by cognitive processes. Using the "McGurk illusion," in
      Experiment 1 we found that audio-visual integration of incongruent audio-visual
      words was higher in older adults than in younger adults, although the recognition
      of either audio- or visual-only presented words was the same across groups. In
      Experiment 2 we tested recall of sentences within which an incongruent audio
      visual speech word was embedded. The overall semantic meaning of the sentence was
      compatible with either one of the unisensory components of the target word and/or
      with the illusory percept. Older participants recalled more illusory audio-visual
      words in sentences than younger adults, however, there was no differential effect
      of word compatibility on recall for the two groups. Our findings suggest that the
      relatively high susceptibility to the audio-visual speech illusion in older
      participants is due more to perceptual than cognitive processing. 

PMID- 24027546
TI  - Macular degeneration affects eye movement behavior during visual search.
AB  - Patients with a scotoma in their central vision (e.g., due to macular
      degeneration, MD) commonly adopt a strategy to direct the eyes such that the
      image falls onto a peripheral location on the retina. This location is referred
      to as the preferred retinal locus (PRL). Although previous research has
      investigated the characteristics of this PRL, it is unclear whether eye movement
      metrics are modulated by peripheral viewing with a PRL as measured during a
      visual search paradigm. To this end, we tested four MD patients in a visual
      search paradigm and contrasted their performance with a healthy control group and
      a healthy control group performing the same experiment with a simulated scotoma.
      The experiment contained two conditions. In the first condition the target was an
      unfilled circle hidden among c-shaped distractors (serial condition) and in the
      second condition the target was a filled circle (pop-out condition). Saccadic
      search latencies for the MD group were significantly longer in both conditions
      compared to both control groups. Results of a subsequent experiment indicated
      that this difference between the MD and the control groups could not be explained
      by a difference in target selection sensitivity. Furthermore, search behavior of
      MD patients was associated with saccades with smaller amplitudes toward the
      scotoma, an increased intersaccadic interval and an increased number of eye
      movements necessary to locate the target. Some of these characteristics, such as
      the increased intersaccadic interval, were also observed in the simulation group,
      which indicate that these characteristics are related to the peripheral viewing
      itself. We suggest that the combination of the central scotoma and peripheral
      viewing can explain the altered search behavior and no behavioral evidence was
      found for a possible reorganization of the visual system associated with the use
      of a PRL. Thus the switch from a fovea-based to a PRL-based reference frame
      impairs search efficiency. 

PMID- 24027545
TI  - A brief review of the role of training in near-tool effects.
AB  - Research suggests that, like near-hand effects, visual targets appearing near the
      tip of a hand-held real or virtual tool are treated differently than other
      targets. This paper reviews neurological and behavioral evidence relevant to near
      tool effects and describes how the effect varies with the functional properties
      of the tool and the knowledge of the participant. In particular, the paper
      proposes that motor knowledge plays a key role in the appearance of near-tool
      effects. 

PMID- 24027547
TI  - Distraction by emotion in early adolescence: affective facilitation and
      interference during the attentional blink.
AB  - This study examined the extent to which early adolescents (aged 10-13 years)
      differ from adults in their sensitivity to attention capture by affective stimuli
      during rapid processing. A rapid serial visual presentation paradigm (RSVP) was
      implemented as a dual task, requiring the report of two green target stimuli
      embedded in a stream of distractors. Known as the "attentional blink" (AB), task
      performance is typically impaired when the first and second targets (T1 and T2,
      respectively) are separated by at least one distractor and about 200 ms of time.
      Here we used written verbs of pleasant, neutral, and unpleasant content as T1
      items, while affectively neutral exemplars served as T2 and distractor events.
      The temporal distance between T1 and T2 was manipulated to contain either one
      distractor (intertarget interval 232 ms) or five distractors (intertarget
      interval 696 ms). Students reported pleasant T1 words more accurately, compared
      to neutral and unpleasant words, indicating facilitation of appetitive content on
      performance during RSVP. Emotional relevance of T1 was at the expense of T2
      accuracy: at an intertarget interval of 232 ms (i.e., during the AB period),
      identification of (neutral) T2 words was impaired when preceded by pleasant and
      unpleasant T1s. No interference across targets was observed, however, beyond the
      blink period, in which T1 and T2 were separated by 696 ms. Thus, emotionally
      relevant events capture and hold attentional resources, at the cost of attentive
      processing in subsequent episodes. Contrary to our findings in adults, these
      capture effects were most obvious when the available capacity was limited, i.e.,
      during the critical interval of the AB. The findings are discussed in light of
      the use of alternative cognitive strategies as development proceeds beyond early
      adolescence into adulthood. 

PMID- 24027548
TI  - Severity of specific language impairment predicts delayed development in number
      skills.
AB  - The extent to which mathematical development is dependent upon language is
      controversial. This longitudinal study investigates the role of language ability
      in children's development of number skills. Participants were 229 children with
      specific language impairment (SLI) who were assessed initially at age 7 and again
      1 year later. All participants completed measures of psycholinguistic development
      (expressive and receptive), performance IQ, and the Basic Number Skills subtest
      of the British Ability Scales. Number skills data for this sample were compared
      with normative population data. Consistent with predictions that language
      impairment would impact on numerical development, average standard scores were
      more than 1 SD below the population mean at both ages. Although the children
      showed improvements in raw scores at the second wave of the study, the
      discrepancy between their scores and the population data nonetheless increased
      over time. Regression analyses showed that, after controlling for the effect of
      PIQ, language skills explained an additional 19 and 17% of the variance in number
      skills for ages 7 and 8, respectively. Furthermore, logistic regression analyses
      revealed that less improvement in the child's language ability over the course of
      the year was associated with a greater odds of a drop in performance in basic
      number skills from 7 to 8 years. The results are discussed in relation to the
      interaction of linguistic and cognitive factors in numerical development and the
      implications for mathematical education. 

PMID- 24027549
TI  - Effects of early language, speech, and cognition on later reading: a mediation
      analysis.
AB  - This longitudinal secondary analysis examined which early language and speech
      abilities are associated with school-aged reading skills, and whether these
      associations are mediated by cognitive ability. We analyzed vocabulary, syntax,
      speech sound maturity, and cognition in a sample of healthy children at age 3
      years (N = 241) in relation to single word reading (decoding), comprehension, and
      oral reading fluency in the same children at age 9-11 years. All predictor
      variables and the mediator variable were associated with the three reading
      outcomes. The predictor variables were all associated with cognitive abilities,
      the mediator. Cognitive abilities partially mediated the effects of language on
      reading. After mediation, decoding was associated with speech sound maturity;
      comprehension was associated with receptive vocabulary; and oral fluency was
      associated with speech sound maturity, receptive vocabulary, and syntax. In
      summary, all of the effects of language on reading could not be explained by
      cognition as a mediator. Specific components of language and speech skills in
      preschool made independent contributions to reading skills 6-8 years later. These
      early precursors to later reading skill represent potential targets for early
      intervention to improve reading. 

PMID- 24027550
TI  - Congruency sequence effects are driven by previous-trial congruency, not previous
      trial response conflict.
AB  - Congruency effects in distracter interference tasks are often smaller after
      incongruent trials than after congruent trials. However, the sources of such
      congruency sequence effects (CSEs) are controversial. The conflict monitoring
      model of cognitive control links CSEs to the detection and resolution of response
      conflict. In contrast, competing theories attribute CSEs to attentional or
      affective processes that vary with previous-trial congruency (incongruent vs.
      congruent). The present study sought to distinguish between conflict monitoring
      and congruency-based accounts of CSEs. To this end, we determined whether CSEs
      are driven by previous-trial reaction time (RT)-a putative measure of response
      conflict-or by previous-trial congruency. In two experiments using a face-word
      Stroop task (n = 49), we found that current-trial congruency effects did not vary
      with previous-trial RT independent of previous-trial congruency. In contrast,
      current-trial congruency effects were influenced by previous-trial congruency
      independent of previous-trial RT. These findings appear more consistent with
      theories that attribute CSEs to non-conflict processes whose recruitment varies
      with previous-trial congruency than with theories that link CSEs to previous
      trial response conflict. 

PMID- 24027551
TI  - Accounting for individual differences in human associative learning.
AB  - Associative learning has provided fundamental insights to understanding
      psychopathology. However, psychopathology occurs along a continuum and as such,
      identification of disruptions in processes of associative learning associated
      with aspects of psychopathology illustrates a general flexibility in human
      associative learning. A handful of studies have looked specifically at individual
      differences in human associative learning, but while much work has concentrated
      on accounting for flexibility in learning caused by external factors, there has
      been limited work considering how to model the influence of dispositional
      factors. This review looks at the range of individual differences in human
      associative learning that have been explored and the attempts to account for, and
      model, this flexibility. To fully understand human associative learning, further
      research needs to attend to the causes of variation in human learning. 

PMID- 24027552
TI  - Dissociating between object affordances and spatial compatibility effects using
      early response components.
AB  - PERCEPTION AND ACTION ARE TIGHTLY LINKED: objects may be perceived not only in
      terms of visual features, but also in terms of possibilities for action. Previous
      studies showed that when a centrally located object has a salient graspable
      feature (e.g., a handle), it facilitates motor responses corresponding with the
      feature's position. However, such so-called affordance effects have been
      criticized as resulting from spatial compatibility effects, due to the visual
      asymmetry created by the graspable feature, irrespective of any affordances. In
      order to dissociate between affordance and spatial compatibility effects, we
      asked participants to perform a simple reaction-time task to typically graspable
      and non-graspable objects with similar visual features (e.g., lollipop and stop
      sign). Responses were measured using either electromyography (EMG) on proximal
      arm muscles during reaching-like movements, or with finger key-presses. In both
      EMG and button press measurements, participants responded faster when the object
      was either presented in the same location as the responding hand, or was
      affordable, resulting in significant and independent spatial compatibility and
      affordance effects, but no interaction. Furthermore, while the spatial
      compatibility effect was present from the earliest stages of movement preparation
      and throughout the different stages of movement execution, the affordance effect
      was restricted to the early stages of movement execution. Finally, we tested a
      small group of unilateral arm amputees using EMG, and found residual spatial
      compatibility but no affordance, suggesting that spatial compatibility effects do
      not necessarily rely on individuals' available affordances. Our results show
      dissociation between affordance and spatial compatibility effects, and suggest
      that rather than evoking the specific motor action most suitable for interaction
      with the viewed object, graspable objects prompt the motor system in a general,
      body-part independent fashion.

PMID- 24027554
TI  - Challenges in translating academic research into therapeutic advancement.

PMID- 24027553
TI  - Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer
      disease.
AB  - One of the defining pathological features of Alzheimer disease (AD) is the
      intraneuronal accumulation of tau. The tau that forms these accumulations is
      altered both posttranslationally and conformationally, and there is now
      significant evidence that soluble forms of these modified tau species are the
      toxic entities rather than the insoluble neurofibrillary tangles. However there
      is still noteworthy debate concerning which specific pathological forms of tau
      are the contributors to neuronal dysfunction and death in AD. Given that
      increases in aberrant forms of tau play a role in the neurodegeneration process
      in AD, there is growing interest in understanding the degradative pathways that
      remove tau from the cell, and the selectivity of these different pathways for
      various forms of tau. Indeed, one can speculate that deficits in a pathway that
      selectively removes certain pathological forms of tau could play a pivotal role
      in AD. In this review we will discuss the different proteolytic and degradative
      machineries that may be involved in removing tau from the cell. How deficits in
      these different degradative pathways may contribute to abnormal accumulation of
      tau in AD will also be considered. In addition, the issue of the selective
      targeting of specific tau species to a given degradative pathway for clearance
      from the cell will be addressed. 

PMID- 24027556
TI  - Designing artificial environments for preterm infants based on circadian studies
      on pregnant uterus.
AB  - Using uterine explants from Per1::Luc rats and in situ hybridization, we recently
      reported that the circadian property of the molecular clock in the uterus and
      placenta is stably maintained from non-pregnancy, right through to the end stage
      of pregnancy under regular light-dark (LD) cycles. Despite long-lasting increases
      in progesterone during gestation and an increase in estrogen before delivery, the
      uterus keeps a stable Per1::Luc rhythm throughout the pregnancy. The study
      suggests the importance of stable circadian environments for fetuses to achieve
      sound physiology and intrauterine development. This idea is also supported by
      epidemiological and animal studies, in which pregnant females exposed to repeated
      shifting of the LD cycles have increased rates of reproductive abnormalities and
      adverse pregnancy outcomes. Leading from this, we introduced artificial circadian
      environments with controlled lighting conditions to human preterm infants by
      developing and utilizing a specific light filter which takes advantage of the
      unique characteristics of infants' developing visual photoreceptors. In spite of
      growing evidence of the physiological benefits of nighttime exposure to darkness
      for infant development, many Japanese Neonatal Intensive Care Units (NICUs) still
      prefer to maintain constant light in preparation for any possible emergencies
      concerning infants in incubators. To protect infants from the negative effects of
      constant light on their development in the NICU, we have developed a new device
      similar to a magic mirror, by which preterm infants can be shielded from exposure
      to their visible wavelengths of light even in the constant light conditions of
      the NICU while simultaneously allowing medical care staff to visually monitor
      preterm infants adequately. The device leads to significantly increased infant
      activity during daytime than during night time and better weight gains. 

PMID- 24027557
TI  - Imaging large cohorts of single ion channels and their activity.
AB  - As calcium is the most important signaling molecule in neurons and secretory
      cells, amongst many other cell types, it follows that an understanding of calcium
      channels and their regulation of exocytosis is of vital importance. Calcium
      imaging using calcium dyes such as Fluo3, or FRET-based dyes that have been used
      widely has provided invaluable information, which combined with modeling has
      estimated the subtypes of channels responsible for triggering the exocytotic
      machinery as well as inferences about the relative distances away from vesicle
      fusion sites these molecules adopt. Importantly, new super-resolution microscopy
      techniques, combined with novel Ca(2+) indicators and imaginative imaging
      approaches can now define directly the nano-scale locations of very large cohorts
      of single channel molecules in relation to single vesicles. With combinations of
      these techniques the activity of individual channels can be visualized and
      quantified using novel Ca(2+) indicators. Fluorescently labeled specific channel
      toxins can also be used to localize endogenous assembled channel tetramers.
      Fluorescence lifetime imaging microscopy and other single-photon-resolution
      spectroscopic approaches offer the possibility to quantify protein-protein
      interactions between populations of channels and the SNARE protein machinery for
      the first time. Together with simultaneous electrophysiology, this battery of
      quantitative imaging techniques has the potential to provide unprecedented detail
      describing the locations, dynamic behaviors, interactions, and conductance
      activities of many thousands of channel molecules and vesicles in living cells. 

PMID- 24027555
TI  - Motor cortical plasticity in Parkinson's disease.
AB  - In Parkinson's disease (PD), there are alterations of the basal ganglia (BG)
      thalamocortical networks, primarily due to degeneration of nigrostriatal
      dopaminergic neurons. These changes in subcortical networks lead to plastic
      changes in primary motor cortex (M1), which mediates cortical motor output and is
      a potential target for treatment of PD. Studies investigating the motor cortical
      plasticity using non-invasive transcranial magnetic stimulation (TMS) have found
      altered plasticity in PD, but there are inconsistencies among these studies. This
      is likely because plasticity depends on many factors such as the extent of
      dopaminergic loss and disease severity, response to dopaminergic replacement
      therapies, development of l-DOPA-induced dyskinesias (LID), the plasticity
      protocol used, medication, and stimulation status in patients treated with deep
      brain stimulation (DBS). The influences of LID and DBS on BG and M1 plasticity
      have been explored in animal models and in PD patients. In addition, many other
      factors such age, genetic factors (e.g., brain derived neurotropic factor and
      other neurotransmitters or receptors polymorphism), emotional state, time of the
      day, physical fitness have been documented to play role in the extent of
      plasticity induced by TMS in human studies. In this review, we summarize the
      studies that investigated M1 plasticity in PD and demonstrate how these afore
      mentioned factors affect motor cortical plasticity in PD. We conclude that it is
      important to consider the clinical, demographic, and technical factors that
      influence various plasticity protocols while developing these protocols as
      diagnostic or prognostic tools in PD. We also discuss how the modulation of
      cortical excitability and the plasticity with these non-invasive brain
      stimulation techniques facilitate the understanding of the pathophysiology of PD
      and help design potential therapeutic possibilities in this disorder. 

PMID- 24027558
TI  - Type 3 deiodinase and consumptive hypothyroidism: a common mechanism for a rare
      disease.
AB  - The major product secreted by the thyroid is thyroxine (T4), whereas most of the
      biologically active triiodothyronine (T3) derives from the peripheral conversion
      of T4 into T3. The deiodinase enzymes are involved in activation and inactivation
      of thyroid hormones (THs). Type 1 and type 2 deiodinase (D1 and D2) convert T4
      into T3 whereas D3 degrades T4 and T3 into inactive metabolites and is thus the
      major physiological TH inactivator. The hypothalamic-pituitary-thyroid axis
      maintains circulating TH levels constant, while the deiodinases tissue
      specifically regulate intracellular thyroid status by controlling TH action in a
      precise spatio-temporal fashion. Here we review the data related to the recent
      identification of a paraneoplastic syndrome called "consumptive hypothyroidism,"
      which exemplifies how deiodinases alter substantially the concentration of TH in
      blood. This syndrome results from the aberrant uncontrolled expression of D3 that
      can induce a severe form of hypothyroidism by inactivating T4 and T3 in defined
      tumor tissue. This rare TH insufficiency generally affects patients in the first
      years of life, and has distinct features in terms of diagnosis, treatment, and
      prognosis with respect to other forms of hypothyroidism. 

PMID- 24027560
TI  - Determination of Ghrelin Structure in the Barfin Flounder (Verasper moseri) and
      Involvement of Ingested Fatty Acids in Ghrelin Acylation.
AB  - Ghrelin is a peptide hormone that is acylated with a fatty acid, usually n
      octanoic acid, at the third amino acid (aa) residue (usually a serine or
      threonine), and this acylation is known to be essential for ghrelin activity not
      only in mammals but also in non-mammals, such as fish. However, the modification
      mechanisms of ghrelin modification in fish are not known. In this study, we
      elucidated the structure of ghrelin in a teleost, the barfin flounder (Verasper
      moseri), and determined whether ingested free fatty acids of various chain
      lengths participated in ghrelin acylation. Complementary DNA cloning revealed the
      barfin flounder prepro-ghrelin to be a 106-aa peptide and the mature ghrelin to
      be a 20-aa peptide (GSSFLSPSHKPPNKGKPPRA). However, purification of ghrelin
      peptides from stomach extracts demonstrated that the major form of the hormone
      was a 19-aa decanoylated peptide [GSS(C10:0)FLSPSHKPPNKGKPPR] missing the last
      alanine of the 20-aa peptide. Ingestion of feed enriched with n-heptanoic acid
      (C7), n-octanoic acid (C8), or n-non-anoic acid (C9) changed the modification
      status of the peptide: ingestion of C8 or C9 increased the amount of C8:0 or C9:0
      19-aa ghrelin, respectively, but no C7:0 ghrelin was isolated after ingestion of
      C7. These results indicate that ingested free fatty acids are substrates for
      ghrelin acylation in the barfin flounder, but the types of free fatty acids
      utilized as substrates may be limited. 

PMID- 24027559
TI  - Phase two steroid metabolism and its roles in breast and prostate cancer
      patients.
AB  - Breast and prostate cancer are diseases in which steroids and steroid metabolism
      could markedly influence clinical outcomes for patients. In both malignancies the
      modification of ketone and hydroxyl groups attached to the steroid backbone
      (phase one metabolism) has been examined in detail but the conjugation reactions
      (phase two metabolism) have not been extensively studied. Therefore, in this
      review we aim to summarize phase two metabolism in breast and prostate cancers
      from a number of perspectives, including the impact of variation in serum levels
      of conjugated steroids, tissue, and pathology specific expression of phase two
      enzymes, and consequences of genetic variations of these conjugation enzymes. In
      addition to this biological perspective, we will also address current
      pharmacological efforts to manipulate phase two metabolism as a potential therapy
      for hormone dependent cancers, including clinical trials of STS inhibitors and
      preclinical STS inhibitor development. While this review is not intended to cover
      any one particular area in great technical depth, it is intended as an
      introduction to and/or update on the importance of variance in phase two
      metabolic pathways in breast and prostate cancers. 

PMID- 24027561
TI  - Different forms of ghrelin exhibit distinct biological roles in tilapia.
AB  - Ghrelin has been identified in all vertebrate classes, including sharks. Each
      species possesses multiple forms of ghrelin that vary in peptide length and acyl
      modifications (e.g., n-hexanoic, n-non-anoic, n-octanoic, and n-decanoic acids)
      including des-acyl ghrelin. Octanoylated ghrelin has been shown to be a potent GH
      secretagogue, orexigenic factor, and plays a role in overall metabolism in
      vertebrates. In the tilapia model, octanoylated ghrelin (ghrelin-C8) and
      decanoylated ghrelin (ghrelin-C10) exhibit different biological actions. This
      mini review highlights the current knowledge of the differential actions of
      ghrelin-C8 and ghrelin-C10 from studies in the tilapia model. These findings
      suggest that the multiple forms of ghrelin may exhibit distinct yet complimentary
      actions directed toward maintaining overall energy balance in other vertebrates. 

PMID- 24027563
TI  - Field and lab conditions alter microbial enzyme and biomass dynamics driving
      decomposition of the same leaf litter.
AB  - Fluctuations in climate and edaphic factors influence field decomposition rates
      and preclude a complete understanding of how microbial communities respond to
      plant litter quality. In contrast, laboratory microcosms isolate the intrinsic
      effects of litter chemistry and microbial community from extrinsic effects of
      environmental variation. Used together, these paired approaches provide
      mechanistic insights to decomposition processes. In order to elucidate the
      microbial mechanisms underlying how environmental conditions alter the trajectory
      of decay, we characterized microbial biomass, respiration, enzyme activities, and
      nutrient dynamics during early (<10% mass loss), mid- (10-40% mass loss), and
      late (>40% mass loss) decay in parallel field and laboratory litter bag
      incubations for deciduous tree litters with varying recalcitrance (dogwood <
      maple < maple-oak mixture < oak). In the field, mass loss was minimal (<10%) over
      the first 50 days (January-February), even for labile litter types, despite above
      freezing soil temperatures and adequate moisture during these winter months. In
      contrast, microcosms displayed high C mineralization rates in the first week.
      During mid-decay, the labile dogwood and maple litters in the field had higher
      mass loss per unit enzyme activity than the lab, possibly due to leaching of
      soluble compounds. Microbial biomass to litter mass (B:C) ratios peaked in the
      field during late decay, but B:C ratios declined between mid- and late decay in
      the lab. Thus, microbial biomass did not have a consistent relationship with
      litter quality between studies. Higher oxidative enzyme activities in oak litters
      in the field, and higher nitrogen (N) accumulation in the lab microcosms occurred
      in late decay. We speculate that elevated N suppressed fungal activity and/or
      biomass in microcosms. Our results suggest that differences in microbial biomass
      and enzyme dynamics alter the decay trajectory of the same leaf litter under
      field and lab conditions. 

PMID- 24027564
TI  - Tradeoffs in microbial carbon allocation may mediate soil carbon storage in
      future climates.

PMID- 24027562
TI  - Multidrug resistant commensal Escherichia coli in animals and its impact for
      public health.
AB  - After the era of plentiful antibiotics we are alarmed by the increasing number of
      antibiotic resistant strains. The genetic flexibility and adaptability of
      Escherichia coli to constantly changing environments allows to acquire a great
      number of antimicrobial resistance mechanisms. Commensal strains of E. coli as
      versatile residents of the lower intestine are also repeatedly challenged by
      antimicrobial pressures during the lifetime of their host. As a consequence,
      commensal strains acquire the respective resistance genes, and/or develop
      resistant mutants in order to survive and maintain microbial homeostasis in the
      lower intestinal tract. Thus, commensal E. coli strains are regarded as
      indicators of antimicrobial load on their hosts. This chapter provides a short
      historic background of the appearance and presumed origin and transfer of
      antimicrobial resistance genes in commensal intestinal E. coli of animals with
      comparative information on their pathogenic counterparts. The dynamics,
      development, and ways of evolution of resistance in the E. coli populations
      differ according to hosts, resistance mechanisms, and antimicrobial classes used.
      The most frequent tools of E. coli against a variety of antimicrobials are the
      efflux pumps and mobile resistance mechanisms carried by plasmids and/or other
      transferable elements. The emergence of hybrid plasmids (both resistance and
      virulence) among E. coli is of further concern. Co-existence and co-transfer of
      these "bad genes" in this huge and most versatile in vivo compartment may
      represent an increased public health risk in the future. Significance of
      multidrug resistant (MDR) commensal E. coli seem to be highest in the food animal
      industry, acting as reservoir for intra- and interspecific exchange and a source
      for spread of MDR determinants through contaminated food to humans. Thus, public
      health potential of MDR commensal E. coli of food animals can be a concern and
      needs monitoring and more molecular analysis in the future. 

PMID- 24027565
TI  - Constraints on superoxide mediated formation of manganese oxides.
AB  - Manganese (Mn) oxides are among the most reactive sorbents and oxidants within
      the environment, where they play a central role in the cycling of nutrients,
      metals, and carbon. Recent discoveries have identified superoxide ([Formula: see
      text]) both of biogenic and abiogenic origin as an effective oxidant of Mn(II)
      leading to the formation of Mn oxides. Here we examined the conditions under
      which abiotically produced superoxide led to oxidative precipitation of Mn and
      the solid-phases produced. Oxidized Mn, as both aqueous Mn(III) and Mn(III/IV)
      oxides, was only observed in the presence of active catalase, indicating that
      hydrogen peroxide (H2O2), a product of the reaction of [Formula: see text] with
      Mn(II), inhibits the oxidation process presumably through the reduction of
      Mn(III). Citrate and pyrophosphate increased the yield of oxidized Mn but
      decreased the amount of Mn oxide produced via formation of Mn(III)-ligand
      complexes. While complexing ligands played a role in stabilizing Mn(III), they
      did not eliminate the inhibition of net Mn(III) formation by H2O2. The Mn oxides
      precipitated were highly disordered colloidal hexagonal birnessite, similar to
      those produced by biotically generated superoxide. Yet, in contrast to the large
      particulate Mn oxides formed by biogenic superoxide, abiotic Mn oxides did not
      ripen to larger, more crystalline phases. This suggests that the deposition of
      crystalline Mn oxides within the environment requires a biological, or at least
      organic, influence. This work provides the first direct evidence that, under
      conditions relevant to natural waters, oxidation of Mn(II) by superoxide can
      occur and lead to formation of Mn oxides. For organisms that oxidize Mn(II) by
      producing superoxide, these findings may also point to other microbially mediated
      processes, in particular enzymatic hydrogen peroxide degradation and/or
      production of organic ligand metabolites, that allow for Mn oxide formation. 

PMID- 24027566
TI  - Understanding biocatalyst inhibition by carboxylic acids.
AB  - Carboxylic acids are an attractive biorenewable chemical in terms of their
      flexibility and usage as precursors for a variety of industrial chemicals. It has
      been demonstrated that such carboxylic acids can be fermentatively produced using
      engineered microbes, such as Escherichia coli and Saccharomyces cerevisiae.
      However, like many other attractive biorenewable fuels and chemicals, carboxylic
      acids become inhibitory to these microbes at concentrations below the desired
      yield and titer. In fact, their potency as microbial inhibitors is highlighted by
      the fact that many of these carboxylic acids are routinely used as food
      preservatives. This review highlights the current knowledge regarding the impact
      that saturated, straight-chain carboxylic acids, such as hexanoic, octanoic,
      decanoic, and lauric acids can have on E. coli and S. cerevisiae, with the goal
      of identifying metabolic engineering strategies to increase robustness. Key
      effects of these carboxylic acids include damage to the cell membrane and a
      decrease of the microbial internal pH. Certain changes in cell membrane
      properties, such as composition, fluidity, integrity, and hydrophobicity, and
      intracellular pH are often associated with increased tolerance. The availability
      of appropriate exporters, such as Pdr12, can also increase tolerance. The effect
      on metabolic processes, such as maintaining appropriate respiratory function,
      regulation of Lrp activity and inhibition of production of key metabolites such
      as methionine, are also considered. Understanding the mechanisms of biocatalyst
      inhibition by these desirable products can aid in the engineering of robust
      strains with improved industrial performance. 

PMID- 24027567
TI  - Mesenchymal stem cells in tissue repair.
AB  - The advent of mesenchymal stem cell (MSC)-based therapies for clinical
      therapeutics has been an exciting and new innovation for the treatment of a
      variety of diseases associated with inflammation, tissue damage, and subsequent
      regeneration and repair. Application-based ability to measure MSC potency and
      fate of the cells post-MSC therapy are the variables that confound the use of
      MSCs therapeutics in human diseases. An evaluation of MSC function and
      applications with attention to detail in the preparation as well as quality
      control and quality assurance are only as good as the assays that are developed.
      In vivo measures of efficacy and potency require an appreciation of the overall
      pathophysiology of the model and standardization of outcome measures. The new
      concepts of how MSC's participate in the tissue regeneration and wound repair
      process and further, how this is impacted by estimates of efficacy and potency
      are important new topics. In this regard, this chapter will review some of the in
      vitro and in vivo assays for MSC function and activity and their application to
      the clinical arena. 

PMID- 24027569
TI  - Inferring HIV Escape Rates from Multi-Locus Genotype Data.
AB  - Cytotoxic T-lymphocytes (CTLs) recognize viral protein fragments displayed by
      major histocompatibility complex molecules on the surface of virally infected
      cells and generate an anti-viral response that can kill the infected cells. Virus
      variants whose protein fragments are not efficiently presented on infected cells
      or whose fragments are presented but not recognized by CTLs therefore have a
      competitive advantage and spread rapidly through the population. We present a
      method that allows a more robust estimation of these escape rates from serially
      sampled sequence data. The proposed method accounts for competition between
      multiple escapes by explicitly modeling the accumulation of escape mutations and
      the stochastic effects of rare multiple mutants. Applying our method to serially
      sampled HIV sequence data, we estimate rates of HIV escape that are substantially
      larger than those previously reported. The method can be extended to complex
      escapes that require compensatory mutations. We expect our method to be
      applicable in other contexts such as cancer evolution where time series data is
      also available. 

PMID- 24027570
TI  - Mimicking Protein-Protein Interactions through Peptide-Peptide Interactions: HIV
      1 gp120 and CXCR4.
AB  - We have recently designed a soluble synthetic peptide that functionally mimics
      the HIV-1 coreceptor CXCR4, which is a chemokine receptor that belongs to the
      family of seven-transmembrane GPCRs. This CXCR4 mimetic peptide, termed CX4-M1,
      presents the three extracellular loops (ECLs) of the receptor. In binding assays
      involving recombinant proteins, as well as in cellular infection assays, CX4-M1
      was found to selectively recognize gp120 from HIV-1 strains that use CXCR4 for
      cell entry (X4 tropic HIV-1). Furthermore, anti-HIV-1 antibodies modulate this
      interaction in a molecular mechanism related to that of their impact on the gp120
      CXCR4 interaction. We could now show that the selectivity of CX4-M1 pertains not
      only to gp120 from X4 tropic HIV-1, but also to synthetic peptides presenting the
      V3 loops of these gp120 proteins. The V3 loop is thought to be an essential part
      of the coreceptor binding site of gp120 that contacts the second ECL of the
      coreceptor. We were able to experimentally confirm this notion in binding assays
      using substitution analogs of CX4-M1 and the V3 loop peptides, respectively, as
      well as in cellular infection assays. These results indicate that interactions of
      the HIV-1 Env with coreceptors can be mimicked by synthetic peptides, which may
      be useful to explore these interactions at the molecular level in more detail. 

PMID- 24027568
TI  - Regulation of ras exchange factors and cellular localization of ras activation by
      lipid messengers in T cells.
AB  - The Ras-MAPK signaling pathway is highly conserved throughout evolution and is
      activated downstream of a wide range of receptor stimuli. Ras guanine nucleotide
      exchange factors (RasGEFs) catalyze GTP loading of Ras and play a pivotal role in
      regulating receptor-ligand induced Ras activity. In T cells, three families of
      functionally important RasGEFs are expressed: RasGRF, RasGRP, and Son of
      Sevenless (SOS)-family GEFs. Early on it was recognized that Ras activation is
      critical for T cell development and that the RasGEFs play an important role
      herein. More recent work has revealed that nuances in Ras activation appear to
      significantly impact T cell development and selection. These nuances include
      distinct biochemical patterns of analog versus digital Ras activation,
      differences in cellular localization of Ras activation, and intricate interplays
      between the RasGEFs during distinct T cell developmental stages as revealed by
      various new mouse models. In many instances, the exact nature of these nuances in
      Ras activation or how these may result from fine-tuning of the RasGEFs is not
      understood. One large group of biomolecules critically involved in the control of
      RasGEFs functions are lipid second messengers. Multiple, yet distinct lipid
      products are generated following T cell receptor (TCR) stimulation and bind to
      different domains in the RasGRP and SOS RasGEFs to facilitate the activation of
      the membrane-anchored Ras GTPases. In this review we highlight how different
      lipid-based elements are generated by various enzymes downstream of the TCR and
      other receptors and how these dynamic and interrelated lipid products may fine
      tune Ras activation by RasGEFs in developing T cells. 

PMID- 24027571
TI  - Interferon gamma receptor: the beginning of the journey.
AB  - Our view of endocytosis and membrane trafficking of transmembrane receptors has
      dramatically changed over the last 20 years. Several new endocytic routes have
      been discovered and mechanistically characterized in mammalian cells. Long
      considered as a passive means to terminate signaling through down-regulation of
      the number of activated receptors at the plasma membrane, it is now established
      that receptor endocytosis and endosomal sorting can be directly linked to the
      regulation of intracellular signaling pathways. The functional links between
      membrane trafficking of interferon receptors and JAK/STAT signaling have recently
      begun to be unraveled. These studies raise the exciting possibility that a
      certain level of signal specificity can be achieved through endocytosis and
      selective localization of the activated complexes within cellular membranes. The
      ongoing development of high-resolution cell imaging techniques with better
      spatial and temporal resolution gives new means of deciphering the inherent
      complexity of membrane trafficking and signaling. This should help to better
      comprehend the molecular mechanisms by which endocytosis and endosomal sorting of
      interferon receptors can orchestrate signaling selectivity within the JAK/STAT
      pathway that can be activated by as many as 60 different cytokines, growth
      factors, and hormones. 

PMID- 24027572
TI  - An Altered gp100 Peptide Ligand with Decreased Binding by TCR and CD8alpha
      Dissects T Cell Cytotoxicity from Production of Cytokines and Activation of NFAT.
AB  - Altered peptide ligands (APLs) provide useful tools to study T cell activation
      and potentially direct immune responses to improve treatment of cancer patients.
      To better understand and exploit APLs, we studied the relationship between APLs
      and T cell function in more detail. Here, we tested a broad panel of gp100280-288
      APLs with respect to T cell cytotoxicity, production of cytokines, and activation
      of Nuclear Factor of Activated T cells (NFAT) by human T cells gene-engineered
      with a gp100-HLA-A2-specific TCRalphabeta. We demonstrated that gp100-specific
      cytotoxicity, production of cytokines, and activation of NFAT were not affected
      by APLs with single amino acid substitutions, except for an APL with an amino
      acid substitution at position 3 (APL A3), which did not elicit any T cell
      response. A gp100 peptide with a double amino acid mutation (APL S4S6) elicited T
      cell cytotoxicity and production of IFNgamma, and to a lesser extent TNFalpha, IL
      4, and IL-5, but not production of IL-2 and IL-10, or activation of NFAT.
      Notably, T cell receptor (TCR)-mediated functions showed decreases in
      sensitivities for S4S6 versus gp100 wild-type (wt) peptide, which were minor for
      cytotoxicity but at least a 1000-fold more prominent for the production of
      cytokines. TCR-engineered T cells did not bind A3-HLA-A2, but did bind S4S6-HLA
      A2 although to a lowered extent compared to wt peptide-HLA-A2. Moreover, S4S6
      induced T cell function demonstrated an enhanced dependency on CD8alpha. Taken
      together, most gp100 APLs functioned as agonists, but A3 and S4S6 peptides acted
      as a null ligand and partial agonist, respectively. Our results further suggest
      that TCR-mediated cytotoxicity can be dissected from production of cytokines and
      activation of NFAT, and that the agonist potential of peptide mutants relates to
      the extent of binding by TCR and CD8alpha. These findings may facilitate the
      design of APLs to advance the study of T cell activation and their use for
      therapeutic applications. 

PMID- 24027573
TI  - Predicting promoters targeted by TAL effectors in plant genomes: from dream to
      reality.

PMID- 24027574
TI  - The evolution, morphology, and development of fern leaves.
AB  - Leaves are lateral determinate structures formed in a predictable sequence
      (phyllotaxy) on the flanks of an indeterminate shoot apical meristem. The origin
      and evolution of leaves in vascular plants has been widely debated. Being the
      main conspicuous organ of nearly all vascular plants and often easy to recognize
      as such, it seems surprising that leaves have had multiple origins. For decades,
      morphologists, anatomists, paleobotanists, and systematists have contributed data
      to this debate. More recently, molecular genetic studies have provided insight
      into leaf evolution and development mainly within angiosperms and, to a lesser
      extent, lycophytes. There has been recent interest in extending leaf evolutionary
      developmental studies to other species and lineages, particularly in lycophytes
      and ferns. Therefore, a review of fern leaf morphology, evolution and development
      is timely. Here we discuss the theories of leaf evolution in ferns, morphology,
      and diversity of fern leaves, and experimental results of fern leaf development.
      We summarize what is known about the molecular genetics of fern leaf development
      and what future studies might tell us about the evolution of fern leaf
      development. 

PMID- 24027575
TI  - Biomass and morphology of fine roots of sugi (Cryptomeria japonica) after 3 years
      of nitrogen fertilization.
AB  - Increasing nitrogen (N) deposition may affect carbon and nutrient dynamics in
      forest ecosystems. To better understand the effects of N deposition, we need to
      improve our knowledge of N effects on fine roots (roots <2 mm in diameter), as
      they are a key factor in carbon and nutrient dynamics. In this study, we
      fertilized 1 * 2 m plots in a sugi (Cryptomeria japonica) stand (336 kg ha(-) (1)
      y(-) (1)) for 3 years and evaluated the responses of the fine roots to high N
      load. After fertilization, the concentration of NO3-N in the soil of N-fertilized
      (NF) plots was five-times as large as that in the control plots and the effect
      was more remarkable in the subsurface soil than in the surface soil. The biomass
      of fine roots <2 mm in diameter appeared to be greater in the NF plots (88 +/- 19
      g m(-) (2)) than in the control plots (56 +/- 14 g m(-) (2)), but this difference
      was not statistically significant. In both plots, 76% of the biomass was
      accounted for by fine roots that were <1 mm in diameter. In the surface soil, the
      specific root length of fine roots <1 mm in diameter was significantly greater,
      and the diameter of those fine roots was marginally smaller, in the NF plots than
      in the control plots. In addition, the concentration of N in fine roots <1 mm in
      diameter was marginally greater in the NF plots than in the control plots. There
      may have been increased production of thinner fine roots or increased root
      branching in the NF plots. This study suggests that, in general, high N load is
      likely to have positive effects on sugi in terms of fine root characteristics and
      the effects on fine-root morphology are more evident than the effects on fine
      root biomass. 

PMID- 24027576
TI  - A case of podocytic infolding glomerulopathy with focal segmental
      glomerulosclerosis.
AB  - Podocytic infolding glomerulopathy (PIG) has been proposed as a new disease
      entity. A 14-year-old girl underwent renal biopsy at our institution because of a
      chance finding of proteinuria. Light microscopic findings revealed a minor
      glomerular abnormality, but under a higher magnification, after periodic acid
      methenamine silver staining, a bubbling appearance in the glomerular basement
      membrane (GBM) was observed. An electron microscopic examination revealed
      microspheres in the GBM, which were sparse but global. The patient was diagnosed
      as having PIG. After 3 years, her urinary protein had increased and a second
      biopsy was performed, showing focal segmental glomerulosclerosis in addition to a
      lesser degree of podocytic infolding than at the first biopsy. This is the first
      report of a case complicated by a different type of glomerulonephritis after
      being diagnosed as PIG. A few cases of PIG are complicated by focal segmental
      glomerulosclerosis, suggesting several mechanisms for the disorder. 

PMID- 24027578
TI  - Social networks for eHealth solutions on cloud.

PMID- 24027579
TI  - Elders' life stories: impact on the next generation of health professionals.
AB  - The purpose of this study was to pilot an enhanced version of the "Share your
      Life Story" life review writing workshop. The enhanced version included the
      addition of an intergenerational exchange, based on the content of seniors'
      writings, with students planning careers in the health sciences. The researcher
      employed a mixed methods design. Preliminary results using descriptive analysis
      revealed an increase in positive images of aging and a decrease in negative
      images of aging among the five student participants. Qualitative results revealed
      six themes that illuminate the hows and whys of the quantitative results as well
      as additional program benefits. Feedback from students and seniors helped to
      refine the intergenerational protocol for a larger scale study. 

PMID- 24027577
TI  - BLM SUMOylation regulates ssDNA accumulation at stalled replication forks.
AB  - Polymerase stalling results in uncoupling of DNA polymerase and the replicative
      helicase, which generates single-stranded DNA (ssDNA). After stalling, RAD51
      accumulates at stalled replication forks to stabilize the fork and to repair by
      homologous recombination (HR) double-strand breaks (DSBs) that accumulate there.
      We showed recently that SUMO modification of the BLM helicase is required in
      order for RAD51 to accumulate at stalled forks. In order to investigate how BLM
      SUMOylation controls RAD51 accumulation, we characterized the function of HR
      proteins and ssDNA-binding protein RPA in cells that stably expressed either
      normal BLM (BLM+) or SUMO-mutant BLM (SM-BLM). In HU-treated SM-BLM cells,
      mediators BRCA2 and RAD52, which normally substitute RAD51 for RPA on ssDNA,
      failed to accumulate normally at stalled forks; instead, excess RPA accumulated.
      SM-BLM cells also exhibited higher levels of HU-induced chromatin-bound RPA than
      BLM+ cells did. The excess RPA did not result from excessive intrinsic BLM
      helicase activity, because in vitro SUMOylated BLM unwound similar amounts of
      replication-fork substrate as unSUMOylated BLM. Nor did BLM SUMOylation inhibit
      binding of RPA to BLM in vitro; however, in immunoprecipitation experiments, more
      BLM-RPA complex formed in HU-treated SM-BLM cells, indicating that BLM
      SUMOylation controls the amount of BLM-RPA complex normally formed at stalled
      forks. Together, these results showed that BLM SUMOylation regulates the amount
      of ssDNA that accumulates during polymerase stalling. We conclude that BLM
      SUMOylation functions as a licensing mechanism that permits and regulates HR at
      damaged replication forks. 

PMID- 24027580
TI  - Risk factors associated with vancomycin-resistant enterococcus in intensive care
      unit settings in saudi arabia.
AB  - Background. Vancomycin-resistant enterococci (VRE) are significant nosocomial
      pathogens worldwide. There is one report about the epidemiology of VRE in Saudi
      Arabia. Objective. To determine the risk factors associated with VRE infection or
      colonization in intensive care unit (ICU) settings. Design. This is a
      descriptive, epidemiologic hospital-based case-control study of patients with VRE
      from February 2006 to March 2010 in ICU in a tertiary hospital in Saudi Arabia.
      Methods. Data were collected from hospital records of patients with VRE. The main
      outcome measure was the adjusted odds ratio estimates of potential risk factors
      for VRE. Results. Factors associated with VRE included ICU admission for
      multiorgan failure, chronic renal failure, prior use of antimicrobial agents in
      the past three months and before ICU admission, gastrointestinal oral contrast
      procedure, and hemodialysis. Being located in a high risk room (roommate of
      patients colonized or infected with VRE) was found to be protective. Conclusions.
      Factors associated with VRE acquisition are often complex and may be confounded
      by local variables. 

PMID- 24027581
TI  - Diet-regulated anxiety.
AB  - A substantial proportion of noncommunicable disease originates in habitual
      overconsumption of calories, which can lead to weight gain and obesity and
      attendant comorbidities. At the other end of the spectrum, the consequences of
      undernutrition in early life and at different stages of adult life can also have
      major impact on wellbeing and quality of life. To help address some of these
      issues, greater understanding is required of interactions with food and
      contemporary diets throughout the life course and at a number of different
      levels: physiological, metabolic, psychological, and emotional. Here we review
      the current literature on the effects of dietary manipulation on anxiety-like
      behaviour. This evidence, assembled from study of preclinical models of diet
      challenge from gestation to adult life, supports a role for diet in the important
      connections between psychology, physiology, and behaviour. Analogous processes in
      the human population in our current obesogenic environment are likely to
      contribute to individual and societal challenges in this area. 

PMID- 24027582
TI  - Mechanism of the Inhibitory Effects of Eucommia ulmoides Oliv. Cortex Extracts
      (EUCE) in the CCl 4 -Induced Acute Liver Lipid Accumulation in Rats.
AB  - Eucommia ulmoides Oliv. (EU) has been used for treatment of liver diseases. The
      protective effects of Eucommia Ulmoides Oliv. cortex extracts (EUCE) on the
      carbon tetrachloride- (CCl4-) induced hepatic lipid accumulation were examined in
      this study. Rats were orally treated with EUCE in different doses prior to an
      intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4 decreased
      plasma triglyceride but increased hepatic triglyceride and cholesterol as
      compared to control rats. On the other hand, the pretreatment with EUCE
      diminished these effects at a dose-dependent manner. CCl4 treatment decreased
      glutathione (GSH) and increased malondialdehyde (MDA) accompanied by activated
      P450 2E1. The pretreatment with EUCE significantly improved these deleterious
      effects of CCl4. CCl4 treatment increased P450 2E1 activation and ApoB
      accumulation. Pretreatment with EUCE reversed these effects. ER stress response
      was significantly increased by CCl4, which was inhibited by EUCE. One of the
      possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4
      reduced lysosomal enzymes that were reversed with the EUCE. The results indicate
      that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic
      lipid accumulation. ER stress and its related ROS regulation are suggested as a
      possible mechanism in the antidyslipidemic effect of EUCE. 

PMID- 24027583
TI  - Neoadjuvant chemotherapy and targeted therapy in breast cancer: past, present,
      and future.
AB  - Traditionally, neoadjuvant treatment for breast cancer was preserved for locally
      advanced and inflammatory disease, converting an inoperable to a surgical
      resectable cancer. In recent years, neoadjuvant therapy has become an accepted
      treatment option also for lower tumor stages in order to increase the rate of
      breast conserving therapy and to reduce the extent of surgery. Furthermore,
      treatment response can be monitored, and therefore, patient compliance may be
      increased. Neoadjuvant trials, additionally, offer the opportunity to evaluate
      new treatment options in a faster way and with fewer patients than large adjuvant
      trials. Compared to the metastatic setting, the issue of acquired resistance and
      pretreatments, which may distort treatment efficacy, can be avoided. New trial
      designs like window-of-opportunity trials or postneoadjuvant trials provide the
      chance to identify tumor sensitivity or to overcome tumor resistance in early
      tumor stages. In particular, in HER2-positive breast cancer, the neoadjuvant
      approach yielded great successes. The dual HER2 blockade with trastuzumab and
      pertuzumab recently showed the highest pCR rates ever reported. Many new drugs
      are in clinical testing with the aim to further increase pCR rates. Whether this
      endpoint really represents a surrogate for long-term outcome is not answered yet
      and will be discussed in this review. 

PMID- 24027584
TI  - Gene-based antibody strategies for prion diseases.
AB  - Prion diseases or transmissible spongiform encephalopathies (TSE) are a group of
      neurodegenerative and infectious disorders characterized by the conversion of a
      normal cellular protein PrP(C) into a pathological abnormally folded form, termed
      PrP(Sc). There are neither available therapies nor diagnostic tools for an early
      identification of individuals affected by these diseases. New gene-based antibody
      strategies are emerging as valuable therapeutic tools. Among these, intrabodies
      are chimeric molecules composed by recombinant antibody fragments fused to
      intracellular trafficking sequences, aimed at inhibiting, in vivo, the function
      of specific therapeutic targets. The advantage of intrabodies is that they can be
      selected against a precise epitope of target proteins, including protein-protein
      interaction sites and cytotoxic conformers (i.e., oligomeric and fibrillar
      assemblies). Herein, we address and discuss in vitro and in vivo applications of
      intrabodies in prion diseases, focussing on their therapeutic potential. 

PMID- 24027585
TI  - Identification of misfolded proteins in body fluids for the diagnosis of prion
      diseases.
AB  - Transmissible spongiform encephalopathy (TSE) or prion diseases are fatal rare
      neurodegenerative disorders affecting man and animals and caused by a
      transmissible infectious agent. TSE diseases are characterized by spongiform
      brain lesions with neuronal loss and the abnormal deposition in the CNS, and to
      less extent in other tissues, of an insoluble and protease resistant form of the
      cellular prion protein (PrP(C)), named PrP(TSE). In man, TSE diseases affect
      usually people over 60 years of age with no evident disease-associated risk
      factors. In some cases, however, TSE diseases are unequivocally linked to
      infectious episodes related to the use of prion-contaminated medicines, medical
      devices, or meat products as in the variant Creutzfeldt-Jakob disease (CJD).
      Clinical signs occur months or years after infection, and during this silent
      period PrP(TSE), the only reliable marker of infection, is not easily measurable
      in blood or other accessible tissues or body fluids causing public health
      concerns. To overcome the limit of PrP(TSE) detection, several highly sensitive
      assays have been developed, but attempts to apply these techniques to blood of
      infected hosts have been unsuccessful or not yet validated. An update on the
      latest advances for the detection of misfolded prion protein in body fluids is
      provided. 

PMID- 24027586
TI  - Aldehyded Dextran and epsilon -Poly(L-lysine) Hydrogel as Nonviral Gene Carrier.
AB  - Background. The expression term of the gene transfected in cells needs to belong
      enough inorder to make a gene therapy clinically effective. The controlled
      release of the transfected gene can be utilized. The new biodegradable hydrogel
      material created by 20 w/w% aldehyded dextran and 10 w/w% epsilon -poly(L-lysine)
      (ald-dex/PLL) was developed. We examined whether it could be as a nonviral
      carrier of the gene transfer. Methods. A plasmid (Lac-Z) was mixed with ald
      dex/PLL. An in vitro study was performed to assess the expression of Lac-Z with X
      gal stain after gene transfer into the cultured 293 cells and bone marrow cells.
      As a control group, PLL was used as a cationic polymer. Results. We confirmed
      that the transfection efficiency of the ald-dex/PLL had a higher transfection
      efficiency than PLL in 293 cells (plasmid of 2  MU g: ald-dex/PLL 1.1%, PLL
      0.23%, plasmid of 16  MU g: ald-dex/PLL 1.23%, PLL 0.48%). In bone marrow cells,
      we confirmed the expression of Lac-Z by changing the quantity of aldehyded
      dextran. In the groups using ald-dextran of the quantity of 1/4 and 1/12 of PLL,
      their transfection efficiency was 0.43% and 0.41%, respectively. Conclusions.
      This study suggested a potential of using ald-dex/PLL as a non-carrier for gene
      transfer. 

PMID- 24027587
TI  - Dual differentiation-exogenous mesenchymal stem cell therapy for traumatic spinal
      cord injury repair in a murine hemisection model.
AB  - Mesenchymal stem cell (MSC) transplantation has shown tremendous promise as a
      therapy for repair of various tissues of the musculoskeletal, vascular, and
      central nervous systems. Based on this success, recent research in this field has
      focused on complex tissue damage, such as that which occurs from traumatic spinal
      cord injury (TSCI). As the critical event for successful exogenous, MSC therapy
      is their migration to the injury site, which allows for their anti-inflammatory
      and morphogenic effects on fracture healing, neuronal regeneration, and
      functional recover. Thus, there is a need for a cost-effective in vivo model that
      can faithfully recapitulate the salient features of the injury, therapy, and
      recovery. To address this, we review the recent advances in exogenous MSC therapy
      for TSCI and traumatic vertebral fracture repair and the existing challenges
      regarding their translational applications. We also describe a novel murine model
      designed to take advantage of multidisciplinary collaborations between
      musculoskeletal and neuroscience researchers, which is needed to establish an
      efficacious MSC therapy for TSCI. 

PMID- 24027588
TI  - Development of the schedule for multiple parallel "difficult" Peptide synthesis
      on pins.
AB  - Unified schedule for multiple parallel solid-phase synthesis of so-called
      "difficult" peptides on polypropylene pins was developed. Increase in the
      efficiency of 9-fluorenyl(methoxycarbonyl) N-terminal amino-protecting group
      removal was shown to have a greater influence on the accuracy of the "difficult"
      peptide synthesis than the use of more efficient amino acid coupling reagents
      such as aminium salts. Hence the unified schedule for multiple parallel solid
      phase synthesis of "difficult" peptides included the procedure for N-terminal
      amino group deprotection modified by applying a more efficient reagent for the
      deprotection and the standard procedure of amino acid coupling by carbodiimide
      method with an additional coupling using aminium salts, if necessary. Amino acid
      coupling with the help of carbodiimide allows to follow the completeness of the
      coupling via the bromophenol blue indication, thus providing the accuracy of the
      synthesis and preventing an overexpenditure of expensive reagents. About 100
      biotinylated hepatitis C virus envelope protein fragments, most of which
      represented "difficult" peptides, were successfully obtained by synthesis on pins
      with the help of the developed unified schedule. 

PMID- 24027589
TI  - Efficiency of constructed wetland vegetated with Cyperus alternifolius applied
      for municipal wastewater treatment.
AB  - The treatment of municipal wastewater from Yazd city (center of Iran) by
      constructed wetland vegetated with Cyperus alternifolius was assessed. Two
      identical wetlands with a total working volume of 60 L and 10 cm sandy layer at
      the bottom were used. First wetland (W1) was control and had no Cyperus
      alternifolius plant. Second wetland (W2) had 100 Cyperus alternifolius shrubs
      with 40 cm height. Influent wastewater was provided from Yazd's septic tanks
      effluents and after a 4-day retention time in wetlands, reactors effluent was
      sampled for parameters analysis. Results show that chemical oxygen demand (COD),
      NO3 (-)-N, NH4 (+)-N, and PO4 (-3)-P in W1 were reduced to 72%, 88%, 32%, and
      0.8%, and in W2, these parameters were removed in values of 83%, 81%, 47%, and
      10%, respectively. In both wetlands, the highest and lowest removal efficiencies
      were related to COD and phosphorus, respectively. Also, the removed phosphorus
      can be released to stream when the soil saturated or influent phosphorus
      decreased and when the plant died. After a 4-day-retention time, the W2 wetland
      showed a statistically significantly lower COD and NH4 (+)-N in comparison with
      W2 wetland.

PMID- 24027591
TI  - Adaption and application of the four phase trials to traditional chinese
      medicines.
AB  - Four phases of trial are widely used in testing drugs, surgery, and diagnosis in
      Western medicine (WM). The staged testing process helps protect patients from
      unnecessary harms and control costs while assessing safety and efficacy. In this
      paper we adapt the four phase trials for traditional Chinese medicine (TCM). As
      TCM has been used in humans for thousands of years and there has been good
      preliminary clinical evidence on safety and efficacy for many of its therapies,
      in most cases its evaluation can start directly in humans, and preclinical
      laboratory research can be conducted in phase 4 trials after the efficacy is
      firmly demonstrated. Furthermore, unlike investigational drugs, TCM therapies are
      various in the certainty of their safety and efficacy and thus should not enter
      the evaluation process at the same stage. Unlike in WM, clarifying and refining
      PICO (patients, intervention, comparator, and outcome) are an important part of
      evaluation of newly designed TCM therapies. The incommensurability between WM and
      TCM causes additional difficulties in TCM trials regarding defining and choosing
      PICO, for which some suggestions are made. Observational studies seem to have a
      greater role in evaluation for TCM although the efficacy must be confirmed with
      randomized trials. 

PMID- 24027590
TI  - The use of (18)F-FDG-PET/CT for diagnosis and treatment monitoring of
      inflammatory and infectious diseases.
AB  - FDG-PET, combined with CT, is nowadays getting more and more relevant for the
      diagnosis of several infectious and inflammatory diseases and particularly for
      therapy monitoring. Thus, this paper gives special attention to the role of FDG
      PET/CT in the diagnosis and therapy monitoring of infectious and inflammatory
      diseases. Enough evidence in the literature already exists about the usefulness
      of FDG-PET/CT in the diagnosis, management, and followup of patients with
      sarcoidosis, spondylodiscitis, and vasculitis. For other diseases, such as
      inflammatory bowel diseases, rheumatoid arthritis, autoimmune pancreatitis, and
      fungal infections, hard evidence is lacking, but studies also point out that FDG
      PET/CT could be useful. It is of invaluable importance to have large prospective
      multicenter studies in this field to provide clear answers, not only for the
      status of nuclear medicine in general but also to reduce high costs of treatment.

PMID- 24027592
TI  - Effect of the Copaifera langsdorffii Desf. Leaf Extract on the Ethylene Glycol
      Induced Nephrolithiasis in Rats.
AB  - The potential of the Copaifera langsdorffii leaves extract to prevent stone
      formation was analyzed by means of an ethylene glycol (EG) animal model of
      nephrolithiasis and an in vitro crystallization assay. Different doses of the C.
      langsdorffii leaves extract were administered to rats treated with EG. Urine
      biochemical parameters were quantified. CaOx deposits count and analysis of
      osteopontin expression were conducted on kidneys fixed in formalin. The in vitro
      assay was performed by turbidimetry. Phytochemical analyses of the extract were
      accomplished by HPLC-UV-DAD, and several compounds were isolated. C. langsdorffii
      leaf extract was able to avoid stone formation. The number of deposits was 50.30
      +/- 31.29 at the higher extract dose, compared to the value of 179.5 +/- 45.96
      achieved with the EG control. Significantly lower oxalate levels and OPN
      expression and increased citrate levels were observed after extract
      administration. In the in vitro assay, the extract diluted the formed crystals.
      Phytochemical analyses showed that the extract is rich in phenolic compounds that
      are capable of preventing stone formation. Thus, on the basis of our results, we
      suggest that the C. langsdorffii leaf extract has potential application in the
      prevention of kidney stone formation. 

PMID- 24027593
TI  - An Aqueous-Ethanol Extract of Liriope spicata var. prolifera Ameliorates Diabetic
      Nephropathy through Suppression of Renal Inflammation.
AB  - The tuberous root of Liriope spicata var. prolifera (TRLS; Liliaceae family) is
      valued for the ability to promote glucose homeostasis, and it may therefore be
      utilized as an adjuvant therapy in the control of diabetic complications. The aim
      of the present study was to examine the effects of an aqueous ethanol extract
      from TRLS (TRLS-ext) (100 or 200 mg kg(-1) per day for eight weeks) on rats with
      streptozotocin-induced diabetic nephropathy (DN). Renal dysfunction in diabetic
      rats was ameliorated by TRLS-ext as evidenced by reduced creatinine clearance, as
      well as increased blood urea nitrogen and proteinuria. Treatment with TRLS-ext
      was found to markedly improve histological architecture in the diabetic kidney.
      Hyperglycemia induced degradation of inhibitory kappa B and reduced nuclear
      factor kappa B activation, leading to increased infiltration of macrophages and
      increased levels of proinflammatory cytokines, including interleukin-1 and tumor
      necrosis factor- alpha . All of the above abnormalities were reversed by TRLS-ext
      treatment, which also decreased the expression of intercellular adhesion molecule
      1, monocyte chemoattractant protein-1, and fibronectin in the diabetic kidneys.
      These findings provide a perspective on the renoprotective effects of TRLS-ext in
      DN. 

PMID- 24027594
TI  - Berberine Reduces the Metastasis of Chondrosarcoma by Modulating the alpha v beta
      3 Integrin and the PKC delta , c-Src, and AP-1 Signaling Pathways.
AB  - Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to
      invade locally and cause distant metastasis, especially to the lungs. Patients
      diagnosed with chondrosarcoma have poor prognosis. Berberine, an active component
      of the Ranunculaceae and Papaveraceae families of plant, has been proven to
      induce tumor apoptosis and to prevent the metastasis of cancer cells. However,
      the effects of berberine in human chondrosarcoma are largely unknown. In this
      study, we found that berberine did not induce cell apoptosis in human primary
      chondrocytes and chondrosarcoma cells. However, at noncytotoxic concentrations,
      berberine reduced the migration and invasion of chondrosarcoma cancer cells.
      Integrins are the major adhesive molecules in mammalian cells and have been
      associated with the metastasis of cancer cells. We also found that incubation of
      chondrosarcoma cells with berberine reduced mRNA transcription for, and cell
      surface expression of, the alpha v beta 3 integrin, with additional inhibitory
      effects on PKC delta , c-Src, and NF- kappa B activation. Thus, berberine may be
      a novel antimetastasis agent for the treatment of metastatic chondrosarcoma. 

PMID- 24027595
TI  - Specificity of Sensory and Motor Neurons Associated with BL40 and GB30 in the
      Rat: A Dual Fluorescent Labeling Study.
AB  - The purpose of this study is to investigate the specific innervations on
      "Weizhong" (BL40) and "Huantiao" (GB30) by using a dual neural tracing technique.
      After Alexa Fluor 488 and 594 conjugates of cholera toxin subunit B (AF488/594
      CTB) were, respectively, injected into BL40 and GB30 in the same rat, the labeled
      sensory and motor neurons were examined in the rat's dorsal root ganglia (DRGs)
      and spinal cord at thoracic (T) and lumbar (L) segments with a laser scanning
      confocal microscope. In the cases of BL40 injection, AF488-CTB labeled sensory
      and motor neurons were located in L2-6 DRGs and on the mediolateral part of
      spinal ventral horn from L3 to L5 segments, respectively. By contrast, in the
      cases of GB30 injection, AF594-CTB labeled sensory and motor neurons were
      distributed in T13-L6 DRGs and on the anterolateral part of spinal ventral horn
      from L1 to L5 segments, respectively. These results indicate that the sensory and
      motor neurons associated with BL40 and GB30 are located in different spinal
      segments and regions in the nervous system, providing the neuroanatomical
      evidence to serve the specificity of acupoints. 

PMID- 24027596
TI  - Comparative effectiveness of the deqi sensation and non-deqi by moxibustion
      stimulation: a multicenter prospective cohort study in the treatment of knee
      osteoarthritis.
AB  - Substantial evidence has supported that moxibustion stimulates a unique
      phenomenon of Deqi, heat-sensitive moxibustion sensation. This study consisted of
      a multicenter, prospective cohort study with two parallel arms (A: heat-sensitive
      moxibustion sensation group; B: nonheat-sensitive moxibustion sensation group).
      All forms of moxibustion were applied unilaterally on the right leg with a
      triangle shape of three acupuncture points simultaneously (bilateral Xi Yan (EX
      LE5) and He Ding (EX-LE2)). After one month the primary outcome parameter GPCRND
      KOA showed significant differences between groups: trial group 5.23 +/- 2.65
      (adjusted mean +/- SE) 95% CI [4.44~6.01] versus control group 7.43 +/- 2.80
      [6.59~8.26], P = 0.0001. Significant differences were manifested in total M-JOA
      score during the follow-up period (P = 0.0006). Mean knee circumference indicated
      significant difference between the groups (P = 0.03; P = 0.007). Overall, this
      evidence suggested that the effectiveness of the Deqi sensation group might be
      more superior than the non-Deqi sensation one in the treatment of KOA. This study
      was aimed at providing scientific evidence on the Deqi sensation of moxibustion
      and at showing that heat-sensitive moxibustion sensation is essential to achieve
      the preferable treatment effects of KOA. 

PMID- 24027597
TI  - Anti-inflammatory effect of qingpeng ointment in atopic dermatitis-like murine
      model.
AB  - Qingpeng ointment (QP) is a Chinese medicine which has been used in treatment of
      atopic dermatitis (AD) in China. AD-like lesions were induced in BALB/c mice by
      repeated application of 2,4-dinitrofluorobenzene (DNFB) on shaved backs. The mice
      were then treated for 2 weeks with QP of different concentrations and Mometasone
      Furoate cream (MF), respectively. Macroscopic and microscopic changes of the skin
      lesions were observed after the treatment. The levels of serum immunoglobulin
      (Ig) E, tissue interferon (IFN)- gamma , and interleukin (IL)-4 and IL-17A and
      the levels of involucrin, filaggrin, and kallikrein7 in epidermis were measured.
      The results show severe dermatitis with immune profiles similar to human acute
      AD. A significant infiltration of CD4(+) T and mast cells was observed in dermis
      of lesion but inhibited by QP after a 2-week treatment with it. The production of
      IgE, IL-4 and the mRNA expression of IL-17A were also suppressed, but the level
      of IFN- gamma was increased. MF suppressed all production of these cytokines and
      IgE. Accordingly, the mechanism of QP on AD might correlate with its ability of
      modulating the immune dysfunctions rather than suppressing them. It had no effect
      on expressions of involucrin and filaggrin, except that its vehicle decreased the
      level of kallikrein7. 

PMID- 24027598
TI  - Spiritual needs of elderly living in residential/nursing homes.
AB  - While the research on spiritual needs of patients with chronic and life
      threatening diseases increases, there is limited knowledge about psychosocial and
      spiritual needs of elderly living in residential/nursing homes. We were
      interested in which needs were of relevance at all, and how these needs are
      related to life satisfaction and mood states. For that purpose we enrolled 100
      elderly living in residential/nursing homes (mean age 84 +/- 7 years, 82% women)
      and provided standardized questionnaires, that is, Spiritual Needs Questionnaire
      (SpNQ), Brief Multidimensional Life Satisfaction Scale (BMLSS), Quality of Life
      in Elders with Multimorbidity (FLQM) questionnaire, and a mood states scale
      (ASTS). Religious needs and Existential needs were of low relevance, while inner
      peace needs were of some and needs for giving/generativity of highest relevance.
      Regression analyses revealed that the specific needs were predicted best by
      religious trust and mood states, particularly tiredness. However, life
      satisfaction and quality of life were not among the significant predictors. Most
      had the intention to connect with those who will remember them, although they
      fear that there is limited interest in their concerns. It remains an open issue
      how these unmet needs can be adequately supported. 

PMID- 24027599
TI  - Long-Term Regeneration and Functional Recovery of a 15 mm Critical Nerve Gap
      Bridged by Tremella fuciformis Polysaccharide-Immobilized Polylactide Conduits.
AB  - Novel peripheral nerve conduits containing the negatively charged Tremella
      fuciformis polysaccharide (TF) were prepared, and their efficacy in bridging a
      critical nerve gap was evaluated. The conduits were made of poly(D,L-lactide)
      (PLA) with asymmetric microporous structure. TF was immobilized on the lumen
      surface of the nerve conduits after open air plasma activation. The TF-modified
      surface was characterized by the attenuated total reflection Fourier-transformed
      infrared spectroscopy and the scanning electron microscopy. TF modification was
      found to enhance the neurotrophic gene expression of C6 glioma cells in vitro. TF
      modified PLA nerve conduits were tested for their ability to bridge a 15 mm gap
      of rat sciatic nerve. Nerve regeneration was monitored by the magnetic resonance
      imaging. Results showed that TF immobilization promoted the nerve connection in 6
      weeks. The functional recovery in animals receiving TF-immobilized conduits was
      greater than in those receiving the bare conduits during an 8-month period. The
      degree of functional recovery reached ~90% after 8 months in the group of TF
      immobilized conduits. 

PMID- 24027601
TI  - Distributed reconstruction via alternating direction method.
AB  - With the development of compressive sensing theory, image reconstruction from few
      view projections has received considerable research attentions in the field of
      computed tomography (CT). Total-variation- (TV-) based CT image reconstruction
      has been shown to be experimentally capable of producing accurate reconstructions
      from sparse-view data. In this study, a distributed reconstruction algorithm
      based on TV minimization has been developed. This algorithm is very simple as it
      uses the alternating direction method. The proposed method can accelerate the
      alternating direction total variation minimization (ADTVM) algorithm without
      losing accuracy. 

PMID- 24027600
TI  - Membrane curvature recognition by C-reactive protein using lipoprotein mimics.
AB  - It has been reported that the oxidation of phosphatidylcholine (PC) is necessary
      for C-reactive protein (CRP) to bind to lipid membranes, but it remains elusive
      why CRP only binds oxidized membranes. Here we offer a new perspective on the
      role of membrane curvature and CRP binding using engineered lipoprotein particle
      (LPP) mimics. We show that CRP binds preferentially to LPP mimics with diameters
      of <= 28 nm, and binding of CRP to these mimics leads to the dissociation of
      native CRP into monomeric CRP, exposing CRP neo-epitopes that bind C1q. We also
      show that the smaller LPP mimics compete for CRP binding to oxidized low density
      lipoproteins (oxLDLs), suggesting that these mimics expose the same PC epitopes
      as those found on oxLDLs. Results from this study suggest that membrane curvature
      could be an additional factor influencing CRP binding of damaged membranes
      distinct from the oxidation of PC lipids.

PMID- 24027602
TI  - Solutions of a linearized mathematical model for capillary formation in tumor
      angiogenesis: an initial data perturbation approximation.
AB  - We present a mathematical model for capillary formation in tumor angiogenesis and
      solve it by linearizing it using an initial data perturbation method. This method
      is highly effective to obtain solutions of nonlinear coupled differential
      equations. We also provide a specific example resulting, that even a few terms of
      the obtained series solutions are enough to have an idea for the endothelial cell
      movement in a capillary. MATLAB-generated figures are provided, and the stability
      criteria are determined for the steady-state solution of the cell equation. 

PMID- 24027604
TI  - Organizational Structure Reduces Processing Load in the Prefrontal Cortex During
      Discourse Processing of Written Text: Implications for High-Level Reading Issues
      After TBI.
AB  - Adults with traumatic brain injury (TBI) can demonstrate marked difficulty
      producing discourse during story retell and story generation tasks. Changes in
      discourse production have been detailed in terms of fewer content units and
      infrequent use of story grammar elements essential for organization. One
      implication is that poor use of story grammar elements during discourse
      production may signal reduced ability to utilize these elements in other
      communication realms (e.g., reading comprehension). The neural architecture that
      supports discourse organization, primarily the medial prefrontal cortex, is
      particularly susceptible to damage secondary to acquired brain injury. In this
      event related functional magnetic resonance imaging (fMRI) study, we describe
      cortical activation patterns of unimpaired readers as they are presented with
      discourse that is varied in terms of structural organization. The results suggest
      reading discourse with less structure is associated with increased cortical
      activity (e.g., higher processing demands) as compared to reading discourse with
      more traditional structural cues (e.g., story grammar). We discuss cortical areas
      implicated and potential implications for supporting discourse communication in
      persons following TBI.

PMID- 24027603
TI  - Age differences in Exposure and Reactivity to Interpersonal Tensions among Black
      and White Individuals across Adulthood.
AB  - The present study examined age differences in exposure and reactivity to
      interpersonal tensions among White and Black Americans. Participants from the
      National Study of Daily Experiences II (NSDE II, n= 1696 White and n = 239 Black;
      ages 34 to 84) reported their experiences of daily interpersonal tensions and
      well-being (positive and negative affect) over 8 days and provided salivary
      cortisol samples. A total of 40% of respondents reported having an argument and
      62% reported avoiding an argument. Multilevel models estimated separately for
      Black and White respondents revealed that older people reported fewer
      interpersonal tensions (i.e., less exposure) than did younger people. However,
      age differences in reactivity to tensions (e.g., appraisals, coping strategies,
      implications of tensions for affect and cortisol) varied by race. Although older
      Black respondents reported tensions were less stressful than younger Black
      respondents, there were fewer age difference in reactivity to tensions overall
      among Black respondents compared to White respondents. Findings are consistent
      with the exposure reactivity model and gerontological theories of emotion
      regulation but show that the specific age differences vary by race which may
      indicate unique strengths and vulnerabilities among Whites and Blacks.

PMID- 24027605
TI  - Tailoring Plasmon Coupling in Self-Assembled One-Dimensional Au Nanoparticle
      Chains through Simultaneous Control of Size and Gap Separation.
AB  - We investigated the near- and far-field response of one-dimensional chains of Au
      nanoparticles (NPs) fabricated with high structural control through template
      guided self-assembly. We demonstrate that the density of polyethylene glycol
      (PEG) ligands grafted onto the NP surface, in combination with the buffer
      conditions, facilitate a systematic variation of the average gap width (g) at
      short separations of g<1.1nm. The overall size (n) of the cluster was controlled
      through the template. The ability to independently vary n and g allowed for a
      rational tuning of the spectral response in individual NP clusters over a broad
      spectral range. We used this structural control for a systematic investigation of
      the electromagnetic coupling underlying the superradiant cluster mode.
      Independent of the chain length, plasmon coupling is dominated by direct neighbor
      interactions. A decrease in coupling strength at separations ?0.5nm indicates the
      presence of non-local and/or quantum mechanical coupling mechanisms.

PMID- 24027607
TI  - Performance Evaluation of a Differential Phase-contrast Cone-beam (DPC-CBCT)
      System for Soft Tissue Imaging.
AB  - Differential phase-contrast (DPC) technique is promising as the next breakthrough
      in the field of X-ray CT imaging. Utilizing the long ignored X-ray phase
      information, Differential phase-contrast (DPC) technique has the potential of
      providing us with projection images with higher contrast in a CT scan without
      increasing the X-ray dose. While traditional absorption-based X-ray imaging is
      not very efficient at differentiating soft tissues, differential phase-contrast
      (DPC) is promising as a new method to boast the quality of the CT reconstruction
      images in term of contrast noise ratio (CNR) in soft tissue imaging. In order to
      validate and investigate the use of DPC technique in cone-beam CT imaging scheme,
      a new bench-top micro-focus DPC-based cone-beam computed tomography DPC-CBCT
      system has been designed and constructed in our lab for soft tissue imaging. The
      DPC-CBCT system consists of a micro-focus X-ray tube (focal spot 8 MUm), a high
      resolution detector, a rotating phantom holder and two gratings, i.e. a phase
      grating and an analysis. The detector system has a phosphor screen, an optical
      fiber coupling unit and a CMOS chip with an effective pixel pitch of 22.5
      microns. The optical elements are aligned to minimize unexpected moire patterns,
      and system parameters, including tube voltage (or equivalently X-ray spectrum),
      distances between gratings, source-to-object distance and object-to-detector
      distance are chosen as practicable to be applied in a rotating system. The system
      is tested with two simple phantoms for performance evaluation. 3-D volumetric
      phase-coefficients are reconstructed. The performance of the system is compared
      with conventional absorption-based CT in term of contrast noise ratio (CNR) under
      the condition of equal X-ray dose level.

PMID- 24027606
TI  - Feasibility of protein-sparing modified fast by tube (ProMoFasT) in obesity
      treatment: a phase II pilot trial on clinical safety and efficacy (appetite
      control, body composition, muscular strength, metabolic pattern, pulmonary
      function test).
AB  - Anecdotal data in the last few years suggest that protein-sparing modified diet
      (PSMF) delivered by naso-gastric tube enteral (with continuous feeding) could
      attain an significant weight loss and control of appetite oral feeding, but no
      phase II studies on safety and efficacy have been done up to now. To verify the
      safety and efficacy of a protein-sparing modified fast administered by naso
      gastric tube (ProMoFasT) for 10 days followed by 20 days of a low-calorie diet,
      in patients with morbid obesity (appetite control, fat free mass maintenance,
      pulmonary function tests and metabolic pattern, side effects), 26 patients with a
      BMI >=30 kg/m2 have been selected. The patients had to follow a protein-sparing
      fast by enteral nutrition (ProMoFasT) for 24 h/day, for 10 days followed by 20
      days of low-calorie diet (LCD). The endpoint was represented by body weight, BMI,
      abdominal circumference, Haber's appetite test, body composition by body
      impedance assessment (BIA), handgrip strength test, metabolic pattern, pulmonary
      function test. Safety was assessed by evaluation of complications and side
      effects of PSMF and/or enteral nutrition. In this report the results on safety
      and efficacy are described after 10 and 30 days of treatment. After the
      recruiting phase, a total of 22 patients out of 26 enrolled [14 (63.6 %) females]
      were evaluated in this study. Globally almost all clinical parameters changed
      significantly during first 10 days. Total body weight significantly decreased
      after 10 days (?-6.1 +/- 2; p < 0.001) and this decrease is maintained in the
      following 20 days of LCD (? = -5.88 +/- 1.79; p < 0.001). Also the abdominal
      circumference significantly decreased after 10 days [median (range): -4.5 (-30 to
      0); p < 0.001] maintained then in the following 20 days of LCD [median (range) = 
      7 (-23.5 to -2); p < 0.001]. All BIA parameters significantly changed after 10
      and 30 days from baseline. All parameters except BF had a significant change
      after 10 days of treatment while the difference at 30 days was lower than at 10
      days for TBW, FFM and MM with no significant differences from baseline for the
      last two characteristics. For VAS appetite the difference was significant after
      10 days and the decrease in appetite was maintained at 30 days with no
      significant difference (p = 0.83) between 10 and 30 days. No significant
      differences in the first 30 days were detected for PA and for both left and right
      hand grip strength. Particularly, a significant reduction of 1.82 kg in FFM after
      10 days was detected, but not after 30 days. In contrast, a decrease of 3.8 kg of
      BF is observed after 30 days. As far as the respiratory functional tests (RFT)
      are concerned, a significant difference at 10 days was globally observed for
      functional residual capacity (p = 0.012) and expiratory reserve volume (p =
      0.025). There are no reported major complications and side effects resulting from
      the enteral nutrition or PSMF. In particular, cardiac arrhythmias have not been
      reported. From the clinical point of view the PSMF with naso-gastric tube
      (ProMoFasT) method appears safe, it is associated with a significant weight loss
      related to decrease of FM and not to loss of FFM and appetite decreases. It is
      relevant that the RFT are significantly improved after only 10 days suggesting
      the efficacy of this regime in short period, too. These preliminary data
      underline the necessity to increase the number of RCT for this method, which
      could represent a possible alternative to other methodologies, such as the
      intragastric balloon, in particular when it is recommended to improve RFT before
      bariatric, gynecological, orthopedic and lymphatic surgery.

PMID- 24027608
TI  - Automatic Tissue Classification for High-resolution Breast CT Images Based on
      Bilateral Filtering.
AB  - Breast tissue classification can provide quantitative measurements of breast
      composition, density and tissue distribution for diagnosis and identification of
      high-risk patients. In this study, we present an automatic classification method
      to classify high-resolution dedicated breast CT images. The breast is classified
      into skin, fat and glandular tissue. First, we use a multiscale bilateral filter
      to reduce noise and at the same time keep edges on the images. As skin and
      glandular tissue have similar CT values in breast CT images, we use morphologic
      operations to get the mask of the skin based on information of its position.
      Second, we use a modified fuzzy C-mean classification method twice, one for the
      skin and the other for the fatty and glandular tissue. We compared our classified
      results with manually segmentation results and used Dice overlap ratios to
      evaluate our classification method. We also tested our method using added noise
      in the images. The overlap ratios for glandular tissue were above 94. 7% for data
      from five patients. Evaluation results showed that our method is robust and
      accurate.

PMID- 24027609
TI  - 3D Non-rigid Registration Using Surface and Local Salient Features for
      Transrectal Ultrasound Image-guided Prostate Biopsy.
AB  - We present a 3D non-rigid registration algorithm for the potential use in
      combining PET/CT and transrectal ultrasound (TRUS) images for targeted prostate
      biopsy. Our registration is a hybrid approach that simultaneously optimizes the
      similarities from point-based registration and volume matching methods. The 3D
      registration is obtained by minimizing the distances of corresponding points at
      the surface and within the prostate and by maximizing the overlap ratio of the
      bladder neck on both images. The hybrid approach not only capture deformation at
      the prostate surface and internal landmarks but also the deformation at the
      bladder neck regions. The registration uses a soft assignment and deterministic
      annealing process. The correspondences are iteratively established in a fuzzy-to
      deterministic approach. B-splines are used to generate a smooth non-rigid spatial
      transformation. In this study, we tested our registration with pre- and post
      biopsy TRUS images of the same patients. Registration accuracy is evaluated using
      manual defined anatomic landmarks, i.e. calcification. The root-mean-squared
      (RMS) of the difference image between the reference and floating images was
      decreased by 62.6+/-9.1% after registration. The mean target registration error
      (TRE) was 0.88+/-0.16 mm, i.e. less than 3 voxels with a voxel size of
      0.38*0.38*0.38 mm3 for all five patients. The experimental results demonstrate
      the robustness and accuracy of the 3D non-rigid registration algorithm.

PMID- 24027610
TI  - Construction of the Jacobian matrix for fluorescence diffuse optical tomography
      using a perturbation Monte Carlo method.
AB  - Image formation in fluorescence diffuse optical tomography is critically
      dependent on construction of the Jacobian matrix. For clinical and preclinical
      applications, because of the highly heterogeneous characteristics of the medium,
      Monte Carlo methods are frequently adopted to construct the Jacobian.
      Conventional adjoint Monte Carlo method typically compute the Jacobian by
      multiplying the photon density fields radiated from the source at the excitation
      wavelength and from the detector at the emission wavelength. Nonetheless, this
      approach assumes that the source and the detector in Green's function are
      reciprocal, which is invalid in general. This assumption is particularly
      questionable in small animal imaging, where the mean free path length of photons
      is typically only one order of magnitude smaller than the representative
      dimension of the medium. We propose a new method that does not rely on the
      reciprocity of the source and the detector by tracing photon propagation entirely
      from the source to the detector. This method relies on the perturbation Monte
      Carlo theory to account for the differences in optical properties of the medium
      at the excitation and the emission wavelengths. Compared to the adjoint methods,
      the proposed method is more valid in reflecting the physical process of photon
      transport in diffusive media and is more efficient in constructing the Jacobian
      matrix for densely sampled configurations.

PMID- 24027611
TI  - Miniature fiber-optic force sensor for vitreoretinal microsurgery based on low
      coherence Fabry-Perot interferometry.
AB  - Vitreoretinal surgery requires delicate manipulation of retinal tissue. However,
      tool-to-tissue interaction forces in the order of sub-millinewton are usually
      below the human sensory threshold. A surgical force sensor (FS) compatible with
      conventional surgical tools may significantly improve the surgery outcome by
      preventing tissue damage. We have designed and built a miniature FS for
      vitreoretinal surgery using a fiber-optic common-path phase-sensitive optical
      coherence tomography (OCT) system where the distal end of the fiber probe forms a
      low-finesse Fabry-Perot (FP) cavity between the cleaved tip of the lead-in single
      mode fiber and the polished back surface of a stainless steel surgical tool tip.
      To accurately measure the change of the FP cavity length, the cavity is
      interrogated by the fiber-optic common-path phase-sensitive OCT. The FP cavity
      was illuminated with a broadband light source, and the interferometric signal was
      detected using a broadband spectrometer. The phase of the interferometric signal,
      which is proportional to the cavity length change as well as the exerted force,
      was extracted. We have conducted calibration experiments to characterize our one
      dimensional FS. Our result shows that the FS responses linearly to force in axial
      direction with force sensitivity better than 0.25 millinewton.

PMID- 24027612
TI  - Distance-dependent intrinsic fluorescence of proteins on aluminum nanostructures.
AB  - In the past several years we have demonstrated the metal-enhanced fluorescence
      (MEF) and the significant changes in the photophysical properties of fluorophores
      in the presence of metallic nanostructures and nanoparticles using ensemble
      spectroscopic studies. In the represented study, we explored the distance effect
      on intrinsic fluorescence of proteins adsorbed on our layer-by-layer assembled
      metallic nanostructures. The study is expected to provide more information on the
      importance of positioning the proteins at a particular distance for enhanced
      fluorescence from metallic structures. For the present study, we considered using
      easy and inexpensive LbL technique to provide well-defined distance from metallic
      surface. The explored proteins were adsorbed on different numbers of alternate
      layers of poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH).
      SA and BSA were electrostatically attached to the positively charged PAH layer.
      We obtained a maximum of ~11-fold and 9-fold increase in fluorescence intensity
      from SA and BSA, respectively. And also we observed ~3-fold decrease in BSA
      lifetime on metallic nanostructures than those on bare control quartz slides.
      This study reveals the distance dependence of protein fluorescence.

PMID- 24027613
TI  - Fluorescence enhancement using silver-gold nanocomposite substrates.
AB  - Metal-enhanced fluorescence (MEF) is a newly emerging phenomenon in which the
      near-field interactions of fluorophores with the plasmons in metallic
      nanostructures can lead to substantial fluorescence enhancements. In the present
      study, we have investigated the use of silver-gold nanocomposite (Ag-Au-NC)
      structures, prepared by the galvanic replacement reaction of silver with gold, as
      plasmonic substrates for MEF. We have observed significant enhancement in the
      fluorescence intensities and decrease in the fluorescence lifetimes of two
      commonly used dyes, ATTO655 and Cy5, using the fabricated Ag-Au-NC substrates.
      Interestingly, the fluorescence enhancement depends on the amount of residual
      silver present in the substrates after the galvanic replacement reaction. Our
      results show that the galvanic replacement reaction is a very facile and powerful
      route to prepare Ag-Au-NC substrates that can be suitable for various MEF based
      applications.

PMID- 24027614
TI  - Plasmon-controlled fluorescence and single DNA strand sequenching.
AB  - During the past several years we have studied the effects of metallic surfaces
      and nanostructures with fluorophores. We have demonstrated the metal-enhanced
      fluorescence (MEF) and the significant changes in the photophysical properties of
      fluorophores in the presence of metallic nanostructures and nanoparticles using
      ensemble spectroscopic studies. These studies have shown dramatic increases in
      brightness and photostability, especially for low quantum yield fluorophores.
      Much of this work was performed using visible or NIR fluorophores. In the present
      study, we have extended our studies to UV wavelengths and have shown that
      aluminum and platinum particles can enhance the emission of UV fluorophores
      including intrinsic protein fluorescence from 300 to 420 nm. We used the finite
      difference timedomain (FDTD) method to calculate the effects of aluminum
      nanoparticles on nearby fluorophores that emit in the UV. And also we performed
      experiments to investigate the effect of metallic nanoparticles on fluorescence
      intensity of DNA bases and DNA G-quadruplex. We observed increase in fluorescence
      intensities of DNA bases varied range changing from 20 to 3-fold in steady-state
      fluorescence emission measurements. We obtained ~5-fold increase in fluorescence
      intensity of DNA G-quadruplex on both Al and Pt metallic substrates when compared
      with control quartz substrates.

PMID- 24027615
TI  - Visual Discomfort and the Temporal Properties of the Vergence-Accommodation
      Conflict.
AB  - The vergence-accommodation conflict associated with viewing stereoscopic 3D (S3D)
      content can cause visual discomfort. Previous studies of vergence and
      accommodation have shown that the coupling between the two responses is driven by
      a fast, phasic component. We investigated how the temporal properties of vergence
      accommodation conflicts affect discomfort. Using a unique volumetric display, we
      manipulated the stimulus to vergence and the stimulus to accommodation
      independently. There were two experimental conditions: 1) natural viewing in
      which the stimulus to vergence was perfectly correlated with the stimulus to
      accommodation; and 2) conflict viewing in which the stimulus to vergence varied
      while the stimulus to accommodation remained constant (thereby mimicking S3D
      viewing). The stimulus to vergence (and accommodation in natural viewing) varied
      at one of three temporal frequencies in those conditions. The magnitude of the
      conflict was the same for all three frequencies. The young adult subjects
      reported more visual discomfort when vergence changes were faster, particularly
      in the conflict condition. Thus, the temporal properties of the vergence
      accommodation conflict in S3D media affect visual discomfort. The results can
      help content creators minimize discomfort by making conflict changes sufficiently
      slow.

PMID- 24027616
TI  - Use of a graphics processing unit (GPU) to facilitate real-time 3D graphic
      presentation of the patient skin-dose distribution during fluoroscopic
      interventional procedures.
AB  - We have developed a dose-tracking system (DTS) that calculates the radiation dose
      to the patient's skin in real-time by acquiring exposure parameters and imaging
      system-geometry from the digital bus on a Toshiba Infinix C-arm unit. The
      cumulative dose values are then displayed as a color map on an OpenGL-based 3D
      graphic of the patient for immediate feedback to the interventionalist.
      Determination of those elements on the surface of the patient 3D-graphic that
      intersect the beam and calculation of the dose for these elements in real time
      demands fast computation. Reducing the size of the elements results in more
      computation load on the computer processor and therefore a tradeoff occurs
      between the resolution of the patient graphic and the real-time performance of
      the DTS. The speed of the DTS for calculating dose to the skin is limited by the
      central processing unit (CPU) and can be improved by using the parallel
      processing power of a graphics processing unit (GPU). Here, we compare the
      performance speed of GPU-based DTS software to that of the current CPU-based
      software as a function of the resolution of the patient graphics. Results show a
      tremendous improvement in speed using the GPU. While an increase in the spatial
      resolution of the patient graphics resulted in slowing down the computational
      speed of the DTS on the CPU, the speed of the GPU-based DTS was hardly affected.
      This GPU-based DTS can be a powerful tool for providing accurate, real-time
      feedback about patient skin-dose to physicians while performing interventional
      procedures.

PMID- 24027617
TI  - Dose Reduction Technique Using a Combination of a Region of Interest (ROI)
      Material X-Ray Attenuator and Spatially Different Temporal Filtering for
      Fluoroscopic Interventions.
AB  - We demonstrate a novel approach for achieving patient dose savings during image
      guided neurovascular interventions, involving a combination of a material x-ray
      region of interest (ROI) attenuator and a spatially different ROI temporal
      filtering technique. The part of the image under the attenuator is reduced in
      dose but noisy and less bright due to fewer x-ray quanta reaching the detector,
      as compared to the non-attenuating (or less attenuating) region. First the
      brightness is equalized throughout the image by post processing and then a
      temporal filter with higher weights is applied to the high attenuating region to
      reduce the noise, at the cost of increased lag; however, in the regions where
      less attenuation is present, a lower temporal weight is needed and is applied to
      preserve temporal resolution. A simulation of the technique is first presented on
      an actual image sequence obtained from an endovascular image guided
      interventional (EIGI) procedure. Then the actual implementation of the technique
      with a physical ROI attenuator is presented. Quantitative analysis including
      noise analysis and integral dose calculations are presented to validate the
      proposed technique.

PMID- 24027618
TI  - New head equivalent phantom for task and image performance evaluation
      representative for neurovascular procedures occurring in the Circle of Willis.
AB  - Phantom equivalents of different human anatomical parts are routinely used for
      imaging system evaluation or dose calculations. The various recommendations on
      the generic phantom structure given by organizations such as the AAPM, are not
      always accurate when evaluating a very specific task. When we compared the AAPM
      head phantom containing 3 mm of aluminum to actual neuro-endovascular image
      guided interventions (neuro-EIGI) occurring in the Circle of Willis, we found
      that the system automatic exposure rate control (AERC) significantly
      underestimated the x-ray parameter selection. To build a more accurate phantom
      for neuro-EIGI, we reevaluated the amount of aluminum which must be included in
      the phantom. Human skulls were imaged at different angles, using various
      angiographic exposures, at kV's relevant to neuro-angiography. An aluminum step
      wedge was also imaged under identical conditions, and a correlation between the
      gray values of the imaged skulls and those of the aluminum step thicknesses was
      established. The average equivalent aluminum thickness for the skull samples for
      frontal projections in the Circle of Willis region was found to be about 13 mm.
      The results showed no significant changes in the average equivalent aluminum
      thickness with kV or mAs variation. When a uniform phantom using 13 mm aluminum
      and 15 cm acrylic was compared with an anthropomorphic head phantom the x-ray
      parameters selected by the AERC system were practically identical. These new
      findings indicate that for this specific task, the amount of aluminum included in
      the head equivalent must be increased substantially from 3 mm to a value of 13
      mm.

PMID- 24027619
TI  - Graphics Processing Unit (GPU) implementation of image processing algorithms to
      improve system performance of the Control, Acquisition, Processing, and Image
      Display System (CAPIDS) of the Micro-Angiographic Fluoroscope (MAF).
AB  - We present the image processing upgrades implemented on a Graphics Processing
      Unit (GPU) in the Control, Acquisition, Processing, and Image Display System
      (CAPIDS) for the custom Micro-Angiographic Fluoroscope (MAF) detector. Most of
      the image processing currently implemented in the CAPIDS system is pixel
      independent; that is, the operation on each pixel is the same and the operation
      on one does not depend upon the result from the operation on the other, allowing
      the entire image to be processed in parallel. GPU hardware was developed for this
      kind of massive parallel processing implementation. Thus for an algorithm which
      has a high amount of parallelism, a GPU implementation is much faster than a CPU
      implementation. The image processing algorithm upgrades implemented on the CAPIDS
      system include flat field correction, temporal filtering, image subtraction,
      roadmap mask generation and display window and leveling. A comparison between the
      previous and the upgraded version of CAPIDS has been presented, to demonstrate
      how the improvement is achieved. By performing the image processing on a GPU,
      significant improvements (with respect to timing or frame rate) have been
      achieved, including stable operation of the system at 30 fps during a fluoroscopy
      run, a DSA run, a roadmap procedure and automatic image windowing and leveling
      during each frame.

PMID- 24027620
TI  - Automatic 3D Segmentation of the Kidney in MR Images Using Wavelet Feature
      Extraction and Probability Shape Model.
AB  - Numerical estimation of the size of the kidney is useful in evaluating conditions
      of the kidney, especially, when serial MR imaging is performed to evaluate the
      kidney function. This paper presents a new method for automatic segmentation of
      the kidney in three-dimensional (3D) MR images, by extracting texture features
      and statistical matching of geometrical shape of the kidney. A set of Wavelet
      based support vector machines (W-SVMs) is trained on the MR images. The W-SVMs
      capture texture priors of MRI for classification of the kidney and non-kidney
      tissues in different zones around the kidney boundary. In the segmentation
      procedure, these W-SVMs are trained to tentatively label each voxel around the
      kidney model as a kidney or non-kidney voxel by texture matching. A probability
      kidney model is created using 10 segmented MRI data. The model is initially
      localized based on the intensity profiles in three directions. The weight
      functions are defined for each labeled voxel for each Wavelet-based, intensity
      based, and model-based label. Consequently, each voxel has three labels and three
      weights for the Wavelet feature, intensity, and probability model. Using a 3D
      edge detection method, the model is re-localized and the segmented kidney is
      modified based on a region growing method in the model region. The probability
      model is re-localized based on the results and this loop continues until the
      segmentation converges. Experimental results with mouse MRI data show the good
      performance of the proposed method in segmenting the kidney in MR images.

PMID- 24027621
TI  - Variability of the temporal bone surface's topography: implications for otologic
      surgery.
AB  - Otologic surgery is performed for a variety of reasons including treatment of
      recurrent ear infections, alleviation of dizziness, and restoration of hearing
      loss. A typical ear surgery consists of a tympanomastoidectomy in which both the
      middle ear is explored via a tympanic membrane flap and the bone behind the ear
      is removed via mastoidectomy to treat disease and/or provide additional access.
      The mastoid dissection is performed using a high-speed drill to excavate bone
      based on a pre-operative CT scan. Intraoperatively, the surface of the mastoid
      component of the temporal bone provides visual feedback allowing the surgeon to
      guide their dissection. Dissection begins in "safe areas" which, based on surface
      topography, are believed to be correlated with greatest distance from surface to
      vital anatomy thus decreasing the chance of injury to the brain, large blood
      vessels (e.g. the internal jugular vein and internal carotid artery), the inner
      ear, and the facial nerve. "Safe areas" have been identified based on surgical
      experience with no identifiable studies showing correlation of the surface with
      subsurface anatomy. The purpose of our study was to investigate whether such a
      correlation exists. Through a three-step registration process, we defined a
      correspondence between each of twenty five clinically-applicable temporal bone CT
      scans of patients and an atlas and explored displacement and angular differences
      of surface topography and depth of critical structures from the surface of the
      skull. The results of this study reflect current knowledge of osteogenesis and
      anatomy. Based on two features (distance and angular difference), two regions
      (suprahelical and posterior) of the temporal bone show the least variability
      between surface and subsurface anatomy.

PMID- 24027622
TI  - 3D Prostate Segmentation of Ultrasound Images Combining Longitudinal Image
      Registration and Machine Learning.
AB  - We developed a three-dimensional (3D) segmentation method for transrectal
      ultrasound (TRUS) images, which is based on longitudinal image registration and
      machine learning. Using longitudinal images of each individual patient, we
      register previously acquired images to the new images of the same subject. Three
      orthogonal Gabor filter banks were used to extract texture features from each
      registered image. Patient-specific Gabor features from the registered images are
      used to train kernel support vector machines (KSVMs) and then to segment the
      newly acquired prostate image. The segmentation method was tested in TRUS data
      from five patients. The average surface distance between our and manual
      segmentation is 1.18 +/- 0.31 mm, indicating that our automatic segmentation
      method based on longitudinal image registration is feasible for segmenting the
      prostate in TRUS images.

PMID- 24027623
TI  - Lung imaging in rodents using dual energy micro-CT.
AB  - Dual energy CT imaging is expected to play a major role in the diagnostic arena
      as it provides material decomposition on an elemental basis. The purpose of this
      work is to investigate the use of dual energy micro-CT for the estimation of
      vascular, tissue, and air fractions in rodent lungs using a post-reconstruction
      three-material decomposition method. We have tested our method using both
      simulations and experimental work. Using simulations, we have estimated the
      accuracy limits of the decomposition for realistic micro-CT noise levels. Next,
      we performed experiments involving ex vivo lung imaging in which intact lungs
      were carefully removed from the thorax, were injected with an iodine-based
      contrast agent and inflated with air at different volume levels. Finally, we
      performed in vivo imaging studies in (n=5) C57BL/6 mice using fast prospective
      respiratory gating in end-inspiration and end-expiration for three different
      levels of positive end-expiratory pressure (PEEP). Prior to imaging, mice were
      injected with a liposomal blood pool contrast agent. The mean accuracy values
      were for Air (95.5%), Blood (96%), and Tissue (92.4%). The absolute accuracy in
      determining all fraction materials was 94.6%. The minimum difference that we
      could detect in material fractions was 15%. As expected, an increase in PEEP
      levels for the living mouse resulted in statistically significant increases in
      air fractions at end-expiration, but no significant changes in end-inspiration.
      Our method has applicability in preclinical pulmonary studies where various
      physiological changes can occur as a result of genetic changes, lung disease, or
      drug effects.

PMID- 24027624
TI  - Investigation of metrics to assess vascular flow modifications for diverter
      device designs using hydrodynamics and angiographic studies.
AB  - Intracranial aneurysm treatment with flow diverters (FD) is a new minimally
      invasive approach, recently approved for use in human patients. Attempts to
      correlate the flow reduction observed in angiograms with a parameter related to
      the FD structure have not been totally successful. To find the proper parameter,
      we investigated four porous-media flow models. The models describing the relation
      between the pressure drop and flow velocity that are investigated include the
      capillary theory linear model (CTLM), the drag force linear model (DFLM), the
      simple quadratic model (SQM) and the modified quadratic model (MQM).
      Proportionality parameters are referred to as permeability for the linear models
      and resistance for the quadratic ones. A two stage experiment was performed.
      First, we verified flow model validity by placing six different stainless-steel
      meshes, resembling FD structures, in known flow conditions. The best flow model
      was used for the second stage, where six different FD's were inserted in aneurysm
      phantoms and flow modification was estimated using angiographically derived time
      density curves (TDC). Finally, TDC peak variation was compared with the FD
      parameter. Model validity experiments indicated errors of: 70% for the linear
      models, 26% for the SQM and 7% for the MQM. The resistance calculated according
      to the MQM model correlated well with the contrast flow reduction. Results
      indicate that resistance calculated according to MQM is appropriate to
      characterize the FD and could explain the flow modification observed in
      angiograms.

PMID- 24027625
TI  - Combined SPHARM-PDM and entropy-based particle systems shape analysis framework.
AB  - DESCRIPTION OF PURPOSE: The NA-MIC SPHARM-PDM Toolbox represents an automated set
      of tools for the computation of 3D structural statistical shape analysis. SPHARM
      PDM solves the correspondence problem by defining a first order ellipsoid
      aligned, uniform spherical parameterization for each object with correspondence
      established at equivalently parameterized points. However, SPHARM correspondence
      has shown to be inadequate for some biological shapes that are not well described
      by a uniform spherical parameterization. Entropy-based particle systems compute
      correspondence by representing surfaces as discrete point sets that does not rely
      on any inherent parameterization. However, they are sensitive to initialization
      and have little ability to recover from initial errors. By combining both
      methodologies we compute reliable correspondences in topologically challenging
      biological shapes. DATA: Diverse subcortical structures cohorts were used,
      obtained from MR brain images. METHODS: The SPHARM-PDM shape analysis toolbox was
      used to compute point based correspondent models that were then used as
      initializing particles for the entropy-based particle systems. The combined
      framework was implemented as a stand-alone Slicer3 module, which works as an end
      to-end shape analysis module. RESULTS: The combined SPHARM-PDM-Particle framework
      has demonstrated to improve correspondence in the example dataset over the
      conventional SPHARM-PDM toolbox. CONCLUSIONS: The work presented in this paper
      demonstrates a two-sided improvement for the scientific community, being able to
      1) find good correspondences among spherically topological shapes, that can be
      used in many morphometry studies 2) offer an end-to-end solution that will
      facilitate the access to shape analysis framework to users without computer
      expertise.

PMID- 24027628
TI  - Therapeutic potential of blocking DDK1 and sclerostin.

PMID- 24027627
TI  - The coupling of Wnt and Frizzled in 3D.

PMID- 24027626
TI  - Perinatal characteristics and breast cancer risk in daughters: a Scandinavian
      population-based study.
AB  - The in utero origins of breast cancer are an increasing focus of research.
      However, the long time period between exposure and disease diagnosis, and the
      lack of standardized perinatal data collection makes this research challenging.
      We assessed perinatal factors, as proxies for in utero exposures, and breast
      cancer risk using pooled, population-based birth and cancer registry data. Birth
      registries provided information on perinatal exposures. Cases were females born
      in Norway, Sweden or Denmark who were subsequently diagnosed with primary,
      invasive breast cancer (n = 1419). Ten controls for each case were selected from
      the birth registries matched on country and birth year (n = 14,190). Relative
      risks (RRs) and 95% confidence intervals (CIs) were estimated using unconditional
      regression models. Breast cancer risk rose 7% (95% CI 2-13%) with every 500 g
      (roughly 1 s.d.) increase in birth weight and 7% for every 1 s.d. increase in
      birth length (95% CI 1-14%). The association with birth length was attenuated
      after adjustment for birth weight, while the increase in risk with birth weight
      remained with adjustment for birth length. Ponderal index and small- and large
      for-gestational-age status were not better predictors of risk than either weight
      or length alone. Risk was not associated with maternal education or age,
      gestational duration, delivery type or birth order, or with several pregnancy
      complications, including preeclampsia. These data confirm the positive
      association between birth weight and breast cancer risk. Other pregnancy
      characteristics, including complications such as preeclampsia, do not appear to
      be involved in later breast carcinogenesis in young women. 

PMID- 24027629
TI  - SNPs could predict fracture risk in Chinese postmenopausal women.

PMID- 24027630
TI  - Potential allelic determinants of vitamin D deficiency.

PMID- 24027631
TI  - Topography of FUS pathology distinguishes late-onset BIBD from aFTLD-U.
AB  - BACKGROUND: Multiple neurodegenerative diseases are characterized by the abnormal
      accumulation of FUS protein including various subtypes of frontotemporal lobar
      degeneration with FUS inclusions (FTLD-FUS). These subtypes include atypical
      frontotemporal lobar degeneration with ubiquitin-positive inclusions (aFTLD-U),
      basophilic inclusion body disease (BIBD) and neuronal intermediate filament
      inclusion disease (NIFID). Despite considerable overlap, certain pathologic
      features including differences in inclusion morphology, the subcellular
      localization of inclusions, and the relative paucity of subcortical FUS pathology
      in aFTLD-U indicate that these three entities represent related but distinct
      diseases. In this study, we report the clinical and pathologic features of three
      cases of aFTLD-U and two cases of late-onset BIBD with an emphasis on the
      anatomic distribution of FUS inclusions. RESULTS: The aFTLD-U cases demonstrated
      FUS inclusions in cerebral cortex, subcortical grey matter and brainstem with a
      predilection for anterior forebrain and rostral brainstem. In contrast, the
      distribution of FUS pathology in late-onset BIBD cases demonstrated a
      predilection for pyramidal and extrapyramidal motor regions with relative sparing
      of cerebral cortex and limbic regions. CONCLUSIONS: The topography of FUS
      pathology in these cases demonstrate the diversity of sporadic FUS inclusion body
      diseases and raises the possibility that late-onset motor neuron disease with
      BIBD neuropathology may exhibit unique clinical and pathologic features.

PMID- 24027633
TI  - Symptom Profile and Severity in a Sample of Nigerians with Psychotic versus
      Nonpsychotic Major Depression.
AB  - The therapeutic strategies in managing patients with psychotic major depression
      (PMD) differ from those with non-psychotic major depression (NMD), because of
      differences in clinical profile and outcome. However, there is underrecognition
      of psychotic symptoms in depressed patients. Previous studies in Western
      population suggest that certain symptom patterns, apart from psychosis which may
      be concealed, can facilitate the discrimination of PMD from NMD. These studies
      may have limited applicability to sub-Saharan Africa due to cross-cultural
      differences in the phenomenology of depression. This study compared the rates and
      severity of depressive symptoms in outpatients with PMD (n = 129) and NMD (n =
      117) using the Structured Clinical Interview for Depression (SCID) and Hamilton
      Depression Rating Scale (HAM-D). Patients with PMD had statistically
      significantly higher rates of suicidal ideation, suicidal attempt, psychomotor
      agitation, insomnia, and reduced appetite. Patients with NMD were more likely to
      manifest psychomotor retardation and somatic symptoms. PMD was associated with
      greater symptom severity. On logistic regression analysis, suicidal ideation,
      psychomotor disturbances, insomnia, and somatic symptoms were predictive of
      diagnostic status. The presence of these symptoms clusters may increase the
      suspicion of occult psychosis in patients with depression, thereby informing
      appropriate intervention strategies. 

PMID- 24027632
TI  - Long-lasting neural circuit dysfunction following developmental ethanol exposure.
AB  - Fetal Alcohol Spectrum Disorder (FASD) is a general diagnosis for those
      exhibiting long-lasting neurobehavioral and cognitive deficiencies as a result of
      fetal alcohol exposure. It is among the most common causes of mental deficits
      today. Those impacted are left to rely on advances in our understanding of the
      nature of early alcohol-induced disorders toward human therapies. Research
      findings over the last decade have developed a model where ethanol-induced
      neurodegeneration impacts early neural circuit development, thereby perpetuating
      subsequent integration and plasticity in vulnerable brain regions. Here we review
      our current knowledge of FASD neuropathology based on discoveries of long-lasting
      neurophysiological effects of acute developmental ethanol exposure in animal
      models. We discuss the important balance between synaptic excitation and
      inhibition in normal neural network function, and relate the significance of that
      balance to human FASD as well as related disease states. Finally, we postulate
      that excitation/inhibition imbalance caused by early ethanol-induced
      neurodegeneration results in perturbed local and regional network signaling and
      therefore neurobehavioral pathology. 

PMID- 24027634
TI  - Nurses' Patient-Centeredness and Perceptions of Care among Medicaid Patients in
      Hospital Obstetrical Units.
AB  - Objective. This study examined to what degree patient-centeredness-measured as an
      underlying ability of obstetrical nurses-influenced Medicaid patients'
      satisfaction with care in hospital obstetrical units. Design. Multigroup
      structural equation modeling design, using three cross-sectional random samples
      (n = 300 each) from the 2003 Press Ganey National Inpatient Database. Setting.
      Self-administered mail surveys. Participants. 900 Medicaid recipients recently
      discharged from inpatient hospital obstetrical units across the United States.
      Methods. Multigroup structural equation modeling was used to test the goodness of
      fit between a hypothesized model based on the Primary Provider Theory and
      patients' ratings of nurses. Results. The model fitted the data well, was stable
      across three random samples, and was sustained when compared to a competing
      model. The patient-centeredness of nurses significantly influenced overall
      patient satisfaction and explained 66% of its variability. When nurses' patient
      centeredness increased by one standard deviation, patients' satisfaction
      increased by 0.80 standard deviation. Conclusion. This study offers a novel
      approach to the measurement of the patient-centeredness of nurses and a paradigm
      for increasing it and its influence on Medicaid patients' satisfaction in
      hospital obstetrical units. 

PMID- 24027635
TI  - No Association between FC gamma R3B Copy Number Variation and Susceptibility to
      Biopsy-Proven Giant Cell Arteritis.
AB  - Objective. To determine the relationship between FCGR3B gene copy number
      variation (CNV) and biopsy proven giant cell arteritis (GCA). Methods. FCGR3B CNV
      was determined in 139 Australian biopsy proven GCA patients and 162 population
      matched controls, using a duplex qPCR assay and RNase P as the reference gene.
      Copy number was determined using Copy Caller software (v.1.0, Applied Biosystems,
      USA). CNV genotypes were classified into 3 groups (<2, 2, 3+) for analysis
      purposes, and analysis was performed using logistic regression. Results. All GCA
      patients had a positive temporal artery biopsy, and the most common presenting
      symptoms were visual disturbance and temporal headache. The mean age of patients
      at biopsy was 74 years (range 51-94) and 88/139 (63%) were female. The frequency
      of low (<2) FCGR3B copy number was comparable between GCA patients (9/139 = 6.5%)
      and controls (10/162 = 6.2%), as was the frequency of high (3+) FCGR3B copy
      number (15/130 (10.8%) in GCA patients versus 13/162 (8.0%) in controls). Overall
      there was no evidence that FCGR3B CNV frequencies differed between GCA patients
      and controls (chi (2) = 0.75, df = 2, P = 0.69). Conclusion. FCGR3B CNV is not
      associated with GCA; however, replicate studies are required. 

PMID- 24027637
TI  - Ambulatory melanoma care patterns in the United States.
AB  - Objective. To examine trends in melanoma visits in the ambulatory care setting.
      Methods. Data from the National Ambulatory Medical Care Survey (NAMCS) from 1979
      to 2010 were used to analyze melanoma visit characteristics including number of
      visits, age and gender of patients, and physician specialty. These data were
      compared to US Census population estimates during the same time period. Results.
      The overall rate of melanoma visits increased (P < 0.0001) at an apparently
      higher rate than the increase in population over this time. The age of patients
      with melanoma visits increased at approximately double the rate (0.47 year per
      interval year, P < 0.0001) of the population increase in age (0.23 year per
      interval year). There was a nonsignificant (P = 0.19) decline in the proportion
      of female patients seen over the study interval. Lastly, ambulatory care has
      shifted towards dermatologists and other specialties managing melanoma patients
      and away from family/internal medicine physicians and general/plastic surgeons.
      Conclusions. The number and age of melanoma visits has increased over time with
      respect to the overall population, mirroring the increase in melanoma incidence
      over the past three decades. These trends highlight the need for further studies
      regarding melanoma management efficiency. 

PMID- 24027638
TI  - An in vitro evaluation of the biological effects of carbon nanotube-coated dental
      zirconia.
AB  - THE PURPOSE OF THIS STUDY IS TO EVALUATE FUNCTIONALIZED MULTIWALLED CARBON
      NANOTUBES (FMWCNTS) AS A POTENTIAL COATING MATERIAL FOR DENTAL ZIRCONIA FROM A
      BIOLOGICAL PERSPECTIVE: its effect on cell proliferation, viability, morphology,
      and the attachment of an osteoblast-like cell. Osteoblast-like (Saos-2) cells
      were seeded on uncoated and fMWCNT-coated zirconia discs and in culture dishes
      that served as controls. The seeding density was 10(4) cells/cm(2), and the cells
      were cultured for 6 days. Cell viability, proliferation and attachment of the
      Saos-2 cells were studied. The results showed that Saos-2 cells were well
      attached to both the uncoated and the fMWCNT-coated zirconia discs. Cell
      viability and proliferation on the fMWCNT-coated zirconia discs were almost the
      same as for the control discs. Better cell attachment was seen on the fMWCNT
      coated than on the uncoated zirconia discs. In conclusion, fMWCNTs seem to be a
      promising coating material for zirconia-based ceramic surfaces to increase the
      roughness and thereby enhance the osseointegration of zirconia implants. 

PMID- 24027636
TI  - Infodemiology and infoveillance of multiple sclerosis in Italy.
AB  - Multiple Sclerosis (MS) is a chronic debilitating disease of probable autoimmune
      inflammatory nature, whose aetiology is not fully understood, despite the many
      efforts and investigations. In this manuscript, we review the concept of
      "Multiple Sclerosis 2.0", that is to say the Internet usage by MS patients, for
      seeking health and disease-related material for self-care and self-management
      purposes, and we introduce a Google Trends-based approach for monitoring MS
      related Google queries and searches, called MS infodemiology and infoveillance.
      Google Trends has already proven to be reliable for infectious diseases
      monitoring, and here we extend its application and potentiality in the field of
      neurological disorders. 

PMID- 24027639
TI  - Maternal Vitamin A Deficiency during Pregnancy and Its Relation with Maternal and
      Neonatal Hemoglobin Concentrations among Poor Egyptian Families.
AB  - Background. Vitamin A deficiency (VAD) during pregnancy represents a major public
      health problem in developing countries. Anemia is a common consequence of VAD. We
      aimed to measure serum retinol concentrations of a sample of poor Egyptian
      mothers and correlate it with their Hb% and cord Hb%. Methods. This cross
      sectional study included 200 healthy mothers and their healthy full term
      newborns. Maternal and cord blood samples were collected for CBC and measurement
      of serum retinol concentrations. Results. Forty-seven mothers (23.5%) had VAD and
      50% were anemic. Mothers with VAD had a significantly lower mean Hb% and a
      significantly higher frequency of anemia (95.7%) compared to mothers without VAD
      (35.9%). The relative risk for anemia among mothers with VAD was 2.7 (CI = 2.12
      3.3). Newborns of mothers with VAD had a significantly lower mean cord Hb%
      compared to newborns of mothers without VAD. Maternal serum retinol
      concentrations were positively correlated with maternal Hb% and cord Hb%.
      Conclusion. Maternal VAD during pregnancy among poor mothers is associated with
      maternal anemia and lower Hb% of newborns at birth. Vitamin A supplementation is
      highly recommended for this vulnerable group. 

PMID- 24027640
TI  - Young registered nurses' intention to leave the profession and professional
      turnover in early career: a qualitative case study.
AB  - In a time of global nursing shortages an alarming number of young registered
      nurses have expressed a willingness to leave the profession. In this qualitative
      case study we investigate in depth why young nurses leave nursing profession and
      reeducate themselves for a new career. The study is based on longitudinal
      interviews of three young registered nurses in Finland. These nurses were first
      interviewed between December 2006 and May 2007, when they were 29-32 years old
      and having an intention to leave the profession. The second interview took place
      four years later, from January 2011 to March 2011 when all of them had made the
      transition to a new career. Data were analyzed in two stages. In the first stage,
      comprehensive career story narratives were formed on the basis of the interviews.
      In the second stage, emerging themes in these stories were compared, contrasted,
      and interpreted in the context of the overall career histories. Nursing as a
      second career choice and demanding work content as well as poor practice
      environment and the inability to identify with the stereotypical images of nurses
      were main themes that emerged from these career stories. The results of this
      interpretative qualitative study reflect a shift toward insights into
      understanding professional turnover as a complex and long-lasting process. 

PMID- 24027642
TI  - New insights into biology, prognostic factors, and current therapeutic strategies
      in chronic lymphocytic leukemia.
AB  - Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation
      and accumulation of mature B lymphocytes. CLL cells show an antiapoptotic
      profile, suggesting the important role of apoptosis inhibition in the disease
      development. However, there is some population of proliferating CLL cells, which
      may also play a role in progression of the disease. There are several newer,
      biological prognostic factors in CLL. Currently, cytogenetic abnormalities with
      different prognostic values seem to be the most biologically relevant. During the
      last decades, the treatment of CLL has been significantly changed. Different
      strategies such as monotherapy with chlorambucil and purine nucleoside analogues
      (PNA) used alone or in combination with cyclophosphamide have been introduced.
      Most recently, immunochemotherapy with anti-CD20 monoclonal antibody, rituximab,
      combined with fludarabine and cyclophosphamide, became a gold standard of first
      line treatment in eligible CLL patients. Currently, new treatment strategies
      including new monoclonal antibodies, bendamustine, lenalidomide, or inhibitors of
      several cell signaling pathways are under clinical studies in resistant/relapsed
      CLL patients. Moreover, allogeneic stem cell transplantation has to be
      considered, especially in younger high risk patients, for example, those who are
      resistant to PNA or those with 17p deletion. In this paper, we present the most
      important recent advances in CLL biology and treatment. 

PMID- 24027641
TI  - Human immunodeficiency virus and pulmonary arterial hypertension.
AB  - Human immunodeficiency virus- (HIV-) related pulmonary arterial hypertension
      (PAH) is a rare complication of HIV infection. The pathophysiology of HIV-related
      PAH is complex, with viral proteins seeming to play the major role. However,
      other factors, such as coinfection with other microorganisms and HIV-related
      systemic inflammation, might also contribute. The clinical presentation of HIV
      related PAH and diagnosis is similar to other forms of pulmonary hypertension.
      Both PAH-specific therapies and HAART are important in HIV-related PAH
      management. Future studies investigating the pathogenesis are needed to discover
      new therapeutic targets and treatments. 

PMID- 24027643
TI  - ERG Protein Expression Is of Limited Prognostic Value in Men with Localized
      Prostate Cancer.
AB  - Background. The prognostic significance of ERG expression in prostate cancer
      (PCA) has generated mixed results. We sought to investigate the prognostic
      significance of ERG expression in a localized cohort of men with PCA. Material
      and Methods. We investigated ERG protein expression in a cohort of 198 men with
      localized PCA. ERG expression was correlated with patients' clinical outcome and
      several pathological parameters, including Gleason score (GS), pathological
      stage, surgical margin, and extra-capsular extension. Results. ERG expression was
      detected in 86/198 (43.4%) patients exclusively in neoplastic epithelium.
      Overall, ERG mean expression intensity was 1.01 +/- 1.27 versus 0.37 +/- 0.83 in
      acinar PCA compared to foamy type PCA (P < 0.001). In HGPIN, ERG intensity levels
      were comparable to those in foamy type PCA (0.13 +/- 0.56) but significantly
      lower than those in acinar PCA (P < 0.001). ERG expression was significantly
      associated with extra-prostatic extension and higher pathological stage and
      showed a trend toward seminal vesicle invasion. Herein, ERG expression was
      documented in 50/131 (38.1%) patients with pT2 versus 30/55 (54.5%) patients with
      pT3 (P = 0.04). ERG association with higher pathological stage was more
      pronounced in patients with GS > 7. Grouping patients into those with GS <= 7
      versus >7, there was no significant association between ERG expression and GS.
      Similarly, no association was present in relation to either surgical margins or
      postsurgical serum PSA levels. Conclusion. We report significant association
      between ERG protein levels and extra-prostatic extension and higher pathological
      stage. ERG expression is not associated with adverse clinical outcome and is of
      limited prognostic value in localized PCA. 

PMID- 24027644
TI  - Multiple cementoblastoma: a rare case report.
AB  - Benign cementoblastoma is a rare ectomesenchymal odontogenic tumor that
      originates from the root of the tooth and that is characterized by the formation
      of cementum-like tissue. A 60-year old man was referred to us complaining of pain
      in his right jaw. The patient underwent TC dental scan of the mandible, which
      highlighted the presence of three well-circumscribed, round, unilocular
      neoformations of radiopaque appearance with a radiotransparent edge, one of which
      was in close contact with the roots of the lower right second molar. Microscopic
      examination of the greater sample consisted, in its central portion, of dense
      mineralized acellular trabeculae of basophilic tissue cement-like, devoid of
      vessels, adhering to the root of the tooth, while peripherally was observed a
      zone of vascularized osteoid surrounded, occasionally, by a thin rim of
      cementoblasts mixed with fibrous tissue and inflammatory elements. This lesion
      was diagnosed as cementoblastoma. The second lesion appeared radiologically and
      histologically entirely identical to cementoblastoma, but it did not show the
      intimate association with the root of involved tooth. After a careful review of
      the literature, the diagnosis of residual cementoblastoma was made. The
      clinicopathologic features, treatment, and prognosis of this rare tumor are here
      discussed for the young dental practitioner. 

PMID- 24027645
TI  - Acute liver failure associated with levetiracetam and lacosamide combination
      treatment for unspecified epileptic disorder.
AB  - Background and Aim. Levetiracetam is a second-generation antiepileptic drug. It
      is approved as an adjunctive treatment of partial onset seizures with or without
      secondary generalization. It is considered safe with less than 1% of patients
      with transient elevations of liver enzymes. Methods. We report a case of acute
      liver failure secondary to Levetiracetam in combination with Lacosamide
      documented with a liver biopsy. Results. Liver biopsy demonstrated acute liver
      injury with a predominant submassive necrosis pattern and features of a drug
      induced hepatitis. Conclusions. This is the first published case of acute liver
      failure due to antiepileptic therapy with Levetiracetam in combination with
      Lacosamide. 

PMID- 24027646
TI  - Recurrent Lower Gastrointestinal Bleeding: Ileal GIST Diagnosed by Video Capsule
      Endoscopy-A Case Report and Literature Review.
AB  - Introduction. Gastrointestinal stromal tumor (GIST) in the ileum is an extremely
      rare cause of recurrent lower gastrointestinal bleeding (GIB). Case Report. An 89
      year-old man was admitted with melana. He had extensive PMH of CAD post
      CABG/AICD, AAA repair, chronic anemia, myelodysplastic syndrome, lung cancer
      after resection, and recurrent GIB. Prior EGDs, colonoscopies, and upper device
      assisted enteroscopy showed duodenal ulcer, A-V malformation s/p cauterization,
      and angioectasia. On admission, Hb was 6.0 g/dL. An endoscopic capsule study
      showed an ulcerated tumor in the ileum. CT showed no distant metastasis. The
      lesion was resected successfully and confirmed as a high-grade GIST. The patient
      was discharged with no further bleeding. Discussion. Early diagnosis for patients
      with ileal GIST is often challenging. Video capsule endoscopy and double balloon
      enteroscopy could be useful diagnostic tools. Surgical removal is the first line
      for a resectable GIST. Imatinib has become the standard therapy. Conclusion. This
      is a unique case of an ileal GIST in a patient with recurrent GIB which was
      diagnosed by video capsule. Complicated medical comorbidities often lead to a
      significant delay in diagnosis. Therefore, we recommend that if GIB does not
      resolve after appropriate treatments for known causes, the alternative diagnosis
      for occult GIB must be considered, including malignancy such as GIST. 

PMID- 24027647
TI  - Concurrent presentation of hodgkin lymphoma and multiple myeloma.
AB  - The simultaneous presentation of the Hodgkin lymphoma and multiple myeloma in the
      absence of prior chemotherapy or radiation is very rare. Here, we discuss a 72
      year-old patient who initially presented with generalized pruritis. Workup led to
      a diagnosis of multiple myeloma which progressed and required treatment. As part
      of his pretreatment workup, an MRI was performed to evaluate skeletal lesions.
      This revealed diffuse and bulky adenopathy which was confirmed by PET. A biopsy
      of an axillary node was consistent with the nodular sclerosing type Hodgkin
      lymphoma. He was treated with adriamycin, bleomycin, vinblastine, and dacarbazine
      (ABVD) chemotherapy * 6 resulting in complete resolution of his adenopathy and
      pruritis as well as improvement in his myeloma. 

PMID- 24027648
TI  - Malignant mesothelioma of the pericardium: a report of two different
      presentations.
AB  - Malignant mesothelioma of the pericardium is a rare and fatal condition that
      clinicians should be aware of due to its variability of clinical manifestation.
      The diagnosis may be delayed as a result of delayed treatment. Here, we report
      two cases of malignant pericardial mesothelioma with two different clinical
      aspects: cardiac tamponade and mimic tuberculous pericarditis. Both patients: may
      have indirect exposure to asbestos. Despite chemotherapy, both patients died at 2
      weeks and 3 months after the diagnosis. Malignant mesothelioma of the pericardium
      is fatal, has a variety of presentation, and may not be related to asbestosis
      exposure. 

PMID- 24027649
TI  - Solitary fibrous tumor of the postcricoid region: a case report and literature
      review.
AB  - Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm that can present
      essentially anywhere in the body. Presentations in the hypopharynx are extremely
      rare with only two previous cases reported. We report the first case of
      postcricoid SFT occurring in a 58-year-old male requiring a microsuspension
      laryngoscopy excision following an unsuccessful transoral robotic attempt. The
      excision was uneventful, and the patient is currently without recurrence. Current
      management strategies of the hypopharyngeal SFT, the unique differential
      diagnosis, and challenges in surgical approaches in the postcricoid region are
      discussed. 

PMID- 24027650
TI  - A case of adrenal metastasis in seminoma.
AB  - We report an uncommon case of testicular cancer with adrenal metastasis without
      retroperitoneal or distant metastatic disease. This situation is highly unusual.
      In fact, no similar case was reported in the literature. Our case is the first
      adrenalectomy that has been performed for secondary localization of testicular
      cancer. After eighteen-month followup, the patient was doing well, with no
      evidence of disease. 

PMID- 24027651
TI  - A Novel Model of Schizophrenia Age-of-Onset Data Challenges the Conventional
      Interpretations of the Discordance in Monozygote Twin Studies.
AB  - The relative importance of genetics and the environment in causing schizophrenia
      is still being debated. Although the high proportion of monozygote cotwins of
      schizophrenia patients who are discordant suggests that there may be a
      significant environmental contribution to the development of schizophrenia, this
      discordance is predicted by an accumulative multimutation model of schizophrenia
      onset constructed here implying a genetic origin of schizophrenia. In this model,
      schizophrenics are viewed as having been born with the genetic susceptibility to
      develop schizophrenia. As susceptible gene carriers age, they randomly accumulate
      the necessary mutations to cause schizophrenia, the last needed mutation
      coinciding with disease onset. The mutation model predicts that the concordance
      rate in monozygote twin studies will monotonically increase with age,
      theoretically approaching 100% given sufficient longevity. In dizygote cotwins of
      schizophrenia patients, the model predicts that at least 71% of cotwins are
      incapable of developing schizophrenia even though every cotwin and their
      schizophrenic twin shared a similar early environment. The multimutation model is
      shown to fit all of the monozygote and dizygote concordance rate data of the
      principle classical twin studies completed before 1970 considered in this paper.
      Thus, the genetic hypothesis of schizophrenia can be tested by bringing these
      studies up to date. 

PMID- 24027652
TI  - Upper extremity freezing and dyscoordination in Parkinson's disease: effects of
      amplitude and cadence manipulations.
AB  - Purpose. Motor freezing, the inability to produce effective movement, is
      associated with decreasing amplitude, hastening of movement, and poor
      coordination. We investigated how manipulations of movement amplitude and cadence
      affect upper extremity (UE) coordination as measured by the phase coordination
      index (PCI)-only previously measured in gait-and freezing of the upper extremity
      (FO-UE) in people with Parkinson's disease (PD) who experience freezing of gait
      (PD + FOG), do not experience FOG (PD-FOG), and healthy controls. Methods. Twenty
      seven participants with PD and 18 healthy older adults made alternating bimanual
      movements between targets under four conditions: Baseline; Fast; Small;
      SmallFast. Kinematic data were recorded and analyzed for PCI and FO-UE events.
      PCI and FO-UE were compared across groups and conditions. Correlations between UE
      PCI, gait PCI, FO-UE, and Freezing of Gait Questionnaire (FOG-Q) were determined.
      Results. PD + FOG had poorer coordination than healthy old during SmallFast. UE
      coordination correlated with number of FO-UE episodes in two conditions and FOG-Q
      score in one. No differences existed between PD-/+FOG in coordination or number
      of FO-UE episodes. Conclusions. Dyscoordination and FO-UE can be elicited by
      manipulating cadence and amplitude of an alternating bimanual task. It remains
      unclear whether FO-UE and FOG share common mechanisms. 

PMID- 24027653
TI  - Antioxidant Activity of Three Honey Samples in relation with Their Biochemical
      Components.
AB  - The antioxidant activities based on the free radical scavenging, reducing power,
      and bleaching inhibition were investigated for the three commonly used honeys in
      Malaysia, namely, tualang, gelam, and acacia honey. The antioxidant capacity of
      the honey samples was correlated with their biochemical constituents such as
      total phenol, total flavonoid content, and total water-soluble vitamins (vitamin
      B1, B2, B3, B9, B12, and vitamin C). The total flavonoid content of honey samples
      was strongly correlated with the three antioxidative processes (r = 0.9276
      0.9910). In contrast, the total water-soluble vitamins was found to be well
      correlated with the free radical scavenging activity (r = 0.8226). Vitamin B3 was
      likely to be in the highest concentration, which covered for 69-80% of the total
      vitamin content. A number of five phenolic acids, three flavonoids, and two
      organic acids had also been detected from the honey samples using UPLC-MS/MS,
      without sugar-removal procedure. 

PMID- 24027654
TI  - Determination of L-argininamide based on water-soluble fluorescent conjugated
      polymer-aptamer.
AB  - Water-soluble fluorescent conjugated polymer is a promising material which could
      be used as an optical platform in highly sensitive molecular sensors. In this
      paper, a simple label-free DNA sensor, which consisted of a poly(3-alkoxy-4
      methylthiophene) and an aptamer, was used to detect L-argininamide (L-Arm). Due
      to the specific binding reaction between L-Arm and its aptamer, the proposed
      method can easily determinate the L-Arm through the recovery of fluorescence
      without any modification. Other ions or similar molecules had little effect on
      the detection. Moreover, there was a linear relationship between fluorescence
      intensity and the concentration of L-Arm. The detection limit of L-Arm was as low
      as 4.7 nM. 

PMID- 24027657
TI  - Correlates of self-reported colorectal cancer screening accuracy in a multi
      specialty medical group practice.
AB  - PURPOSE: We assessed whether accuracy of self-reported screening for colorectal
      cancer (CRC) varied by respondent characteristics or healthcare utilization.
      METHODS: From 2005 to 2007, 857 respondents aged 51 - 74 were recruited from a
      multi-specialty medical group practice to answer a questionnaire about their CRC
      screening (CRCS) behaviors. Self-reports were compared with administrative and
      medical records to assess concordance, sensitivity, specificity, and report-to
      records ratios for overall CRCS (fecal occult blood test, sigmoidoscopy, and/or
      colonoscopy). RESULTS: Concordance was good (>=0.8 to <0.9) or fair (>=0.7 to
      <0.8) for most subgroups; respondents with >5 visits outside the clinic had poor
      (<0.7) concordance. Sensitivity estimates were mostly excellent (>=0.9) or good
      but poor for respondents whose healthcare provider did not advise a specific CRCS
      test. Specificity was poor for the following respondents: 65+ years, males,
      college graduates, family history of CRC, >5 visits outside of the clinic, or
      whose healthcare provider advised a specific CRCS test. Respondents 65+ years and
      with >5 outside visits over-reported CRCS. CONCLUSIONS: With few exceptions, self
      reports of CRCS in an insured population is reasonably accurate across subgroups.
      More work is needed to replicate these findings in diverse settings and
      populations to better understand subgroup differences and improve measures of
      CRCS.

PMID- 24027656
TI  - Notch Signaling Pathway in Pancreatic Cancer Progression.

PMID- 24027655
TI  - Antipsychotics and the Risks of Sudden Cardiac Death and All-Cause Death: Cohort
      Studies in Medicaid and Dually-Eligible Medicaid-Medicare Beneficiaries of Five
      States.
AB  - CONTEXT: Antipsychotic drugs have been linked to QT-interval prolongation, a
      presumed marker of cardiac risk, and torsade de pointes. OBJECTIVE: To examine
      the associations between antipsychotics and 1) outpatient-originated sudden
      cardiac death and ventricular arrhythmia (SD/VA) and 2) all-cause death. DESIGN:
      Two retrospective cohort studies. SETTING: Medicaid programs of California,
      Florida, New York, Ohio and Pennsylvania. PATIENTS: Incident antipsychotic users
      aged 30-75 years. MAIN OUTCOME MEASURES: 1) Incident, first-listed emergency
      department or principal inpatient SD/VA diagnoses; and 2) death reported in the
      Social Security Administration Death Master File. RESULTS: Among 459,614 incident
      antipsychotic users, the incidences of SD/VA and death were 3.4 and 35.1 per
      1,000 person-years, respectively. Compared to olanzapine as the referent,
      adjusted hazard ratios (HRs) for SD/VA were 2.06 (95% CI, 1.20-3.53) for
      chlorpromazine, 1.72 (1.28-2.31) for haloperidol, and 0.73 (0.57-0.93) for
      quetiapine. Adjusted HRs for perphenazine and risperidone were consistent with
      unity. In a subanalysis limited to first prescription exposures, HRs for
      chlorpromazine and haloperidol were further elevated (2.54 [1.07-5.99] and 2.68
      [1.59-4.53], respectively), with the latter exhibiting a dose-response
      relationship. Results for death were similar. CONCLUSIONS: Haloperidol and
      chlorpromazine had less favorable cardiac safety profiles than olanzapine. Among
      atypical agents, risperidone had a similar cardiac safety profile to olanzapine,
      whereas quetiapine was associated with 30% and 20% lower risks of SD/VA and
      death, respectively, compared to olanzapine. These measured risks do not
      correlate well with average QT prolongation, further supporting the notion that
      average QT prolongation may be a poor surrogate of antipsychotic
      arrhythmogenicity.

PMID- 24027658
TI  - Patients with cancer and family caregivers: management of symptoms caused by
      cancer or cancer therapy at home.
AB  - People are diagnosed with cancer sooner nowadays thanks to increased awareness
      and improvements in cancer screenings. Patients are able to live longer due to
      cancer treatment regimens; however, they suffer the consequences of living with
      cancer and therapy-related symptoms. Symptom management is challenging for both
      patients and family caregivers. Therefore, family members must be integrated in
      the patient's care plan. For this review, a literature search was conducted to
      determine what types of interventions were available that involved family members
      of cancer patients with the management of cancer and therapy-related symptoms.
      The following interventions were found that were designed for the family
      caregivers or both the patient and caregiver to aide with symptom management:
      pain intervention program, massage therapy, telephone intervention, self-efficacy
      improvement, coping enhancement and a multidimensional intervention. A positive
      effect was noted in all the studies, but several had no significance in the
      patient intervention group but did in the caregiver intervention group. However,
      studies indicated decreased symptom intensity for various symptoms, decreased
      symptom distress for both the patient and caregiver, increased self-efficacy of
      the family member, and increased satisfaction with certain interventions. Further
      research should be conducted on both existing interventions to better determine
      their effect and on family symptom management of cancer patients as they need
      support from healthcare professionals as well.

PMID- 24027659
TI  - Attenuation of Cyclosporine-Induced Sperm Impairment and Embryotoxicity by
      Crataegus monogyna Fruit Aqueous Extract.
AB  - OBJECTIVE: Cyclosporine (Cs), a cyclic undecapeptide with potent immuno
      suppressive activity, causes several adverse effects including reproductive
      toxicity. This study aims to examine the ability of Crataegus monogyna aqueous
      fruit extract as an antioxidant to protect against Cs-induced reproductive
      toxicity. MATERIALS AND METHODS: In this experimental study, 32 adult male Wistar
      rats were divided into four groups of eight animals each. Rats in two groups
      received 40 mg/kg/day Cs for 45 days by oral gavage. In addition, one of the two
      groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day
      orally four hours after Cs administration. The remaining two groups consisted of
      a vehicle treated control (Cont) group and a Crataegus monogyna control (Cr)
      group. Differences between groups were assessed by analysis of variance (ANOVA)
      using the SPSS software package for Windows. RESULTS: Cs treatment caused a
      signiifcant decrease in sperm count and viability with an increase in DNA damage
      and protamine deifciency of the sperm cells. We observed signiifcant decreases in
      fertilization rate and embryonic development, in addition to an increased rate of
      embryo arrest in Cs-treated rats. Crataegus monogyna co-administration attenuated
      all Cs-induced negative changes in the above-mentioned parameters. CONCLUSION:
      Supplementation with Crataegus monogyna a queous fruit extract could be useful
      against reproductive toxicity during Cs treatment in a rat model.

PMID- 24027660
TI  - The effect of 8-methoxypsoralen on pituitary-gonad axis and ovarian function in
      mice.
AB  - OBJECTIVE: 8-Methoxypsoralen (8-MOP) is a photoactive compound widely used in the
      treatment of proliferate disorders. The present study investigates the effects of
      8-MOP on ovary function and pituitary-gonad axis in mice. MATERIALS AND METHODS:
      : In this experimental analytical study, 45 female Balb/C mice were divided into
      three groups (n=15), control, sham (olive oil injection) and experimental. The
      experimental group were received an intraperitoneal (i.p.) injection of the LD50
      dose of 60 mg/kg 8-MOP. At 30 days after injection, the animals were sacrificed
      while in the proestrus stage and examined for morphological and histological
      changes their ovaries. Blood samples were collected and estrogen, luteinizing
      hormone (LH) and follicle stimulating hormone (FSH) levels were assessed by
      radioimmunoassay. Data were analyzed using one-way ANOVA and the t test. RESULTS:
      The mean levels of estrogen and progesterone in the experimental group
      significantly decreased (p< 0.001). However, there was a significant increase in
      LH and FSH levels in this group compared to the control groups (p< 0.001). The
      mean number and diameter of the corpus luteum (CL) and the number of growing
      follicles in the experimental group significantly reduced compared to the control
      and sham groups (p< 0.001). The mean granulosa thickness in the experimental
      group also significantly decreased compared to the control and sham groups (p<
      0.001). CONCLUSION: Our data indicated that 8-MOP can affect the levels of LH,
      FSH, estrogen and progesterone. Our findings further suggest that consecutive
      doses of 8-MOP may impair the female reproductive tract (or development).

PMID- 24027661
TI  - Caspase-mediated apoptosis in sensory neurons of cultured dorsal root Ganglia in
      adult mouse.
AB  - OBJECTIVE: Sensory neurons in dorsal root ganglia (DRG) undergo apoptosis after
      peripheral nerve injury. The aim of this study was to investigate sensory neuron
      death and the mechanism involved in the death of these neurons in cultured DRG.
      MATERIALS AND METHODS: In this experimental study, L5 DRG from adult mouse were
      dissected and incubated in culture medium for 24, 48, 72 and 96 hours. Freshly
      dissected and cultured DRG were then fixed and sectioned using a cryostat.
      Morphological and biochemical features of apoptosis were investigated using
      fluorescent staining (Propidium iodide and Hoechst 33342) and the terminal
      Deoxynucleotide transferase dUTP nick end labeling (TUNEL) method respectively.
      To study the role of caspases, general caspase inhibitor (Z-VAD.fmk, 100 MUM) and
      immunohistochemistry for activated caspase-3 were used. RESULTS: After 24, 48, 72
      and 96 hours in culture, sensory neurons not only displayed morphological
      features of apoptosis but also they appeared TUNEL positive. The application of Z
      VAD.fmk inhibited apoptosis in these neurons over the same time period. In
      addition, intense activated caspase-3 immunoreactivity was found both in the
      cytoplasm and the nuclei of these neurons after 24 and 48 hours. CONCLUSION:
      Results of the present study show caspase-dependent apoptosis in the sensory
      neurons of cultured DRG from adult mouse.

PMID- 24027662
TI  - Comparison the effects of two monocyte isolation methods, plastic adherence and
      magnetic activated cell sorting methods, on phagocytic activity of generated
      dendritic cells.
AB  - OBJECTIVE: It is believed that monocyte isolation methods and maturation factors
      affect the phenotypic and functional characteristics of resultant dendritic cells
      (DC). In the present study, we compared two monocyte isolation methods, including
      plastic adherence-dendritic cells (Adh-DC) and magnetic activated cell sorting-
      dendritic cells (MACS-DC), and their effects on phagocytic activity of
      differentiated immature DCs (immDCs). MATERIALS AND METHODS: : In this
      experimental study, immDCs were generated from plastic adherence and MACS
      isolated monocytes in the presence of granulocyte-macrophage colony-stimulating
      factor (GM-CSF) and interleukin 4 (IL-4) in five days. The phagocytic activity of
      immDCs was analyzed by fluorescein isothiocyanate (FITC)-conjugated latex bead
      using flow cytometry. One way ANOVA test was used for statistical analysis of
      differences among experimental groups, including Adh-DC and MACS-DC groups.
      RESULTS: We found that phagocytic activity of Adh-DC was higher than MACS-DC,
      whereas the mean fluorescence intensity (MFI) of phagocytic cells was higher in
      MACS-DC (p<0.05). CONCLUSION: : We concluded that it would be important to
      consider phagocytosis parameters of generated DCs before making any decision
      about monocyte isolation methods to have fully functional DCs.

PMID- 24027663
TI  - Relative Biological Effectiveness (RBE) of (131)I Radiation Relative to (60)Co
      Gamma Rays.
AB  - OBJECTIVE: To assess relative biological effectiveness (RBE) of (131)I radiation
      relative to (60)Co gamma rays in glioblastoma spheroid cells. MATERIALS AND
      METHODS: : In this experimental study, glioblastoma spheroid cells were exposed
      to (131)I radiation and (60)Co gamma rays. Radiation induced DNA damage was
      evaluated by alkaline comet assay. Samples of spheroid cells were treated by
      radiation from (131)I for four different periods of time to find the dose
      response equation. Spheroid cells were also exposed by 200 cGy of (60)Co gamma
      rays as reference radiation to induce DNA damage as endpoint. RESULTS: Resulted
      RBE of (131)I radiation relative to (60)Co gamma rays in 100 um giloblastoma
      spheroid cells was equal to 1.16. CONCLUSION: The finding of this study suggests
      that (131)I photons and electrons can be more effective than (60)Co gamma rays to
      produce DNA damage in glioblastoma spheroid cells.

PMID- 24027664
TI  - Effect of basic fibroblast growth factor on orthodontic tooth movement in rats.
AB  - OBJECTIVE: Basic fibroblast growth factor (bFGF) is a cytokine involved in
      angiogenesis, tissue remodeling and stimulation of osteoblasts and osteoclasts.
      The present study assesses the effects of a local injection of bFGF on the rate
      of orthodontic tooth movement. MATERIALS AND METHODS: : In this laboratory animal
      study, we randomly divided 50 rats into 5 groups of 10 rats each. Rats received
      0.02 cc injections of the following doses of bFGF: group A (10 ng), group B (100
      ng) and group C (1000 ng). Group D (positive control) received an orthodontic
      force and injection of 0.02 cc phosphate buffered saline whereas group E
      (negative control) received only the anesthetic drug. A nickel titanium spring
      was bonded to the right maxillary first molar and incisor. After 21 days, the
      rats were sacrificed and the distance between the first and second right molars
      was measured by a leaf gauge with 0.05 mm accuracy. ANOVA and Tukey's HSD
      statistical tests were used for data analysis. RESULTS: The greatest mean value
      of orthodontic tooth movement was 0.7700 mm observed in group C followed by
      0.6633 mm in group B, 0.5333 mm in group A, 0.2550 mm in group D and 0.0217 mm in
      group E. There was a significantly higher rate of tooth movement in the test
      groups compared to the control groups (p<0.05). Among the test groups, the rate
      of tooth movement in group C was significantly higher than group A (p<0.05).
      Weight changes after the intervention were not significant when compared to the
      baseline values, with the exception of group E (p>0.05). CONCLUSION: The effect
      of bFGF on the rate of tooth movement was dose-dependent. Injection of 1000 ng
      bFGF in rats showed the most efficacy.

PMID- 24027665
TI  - Modification and Evaluation of Avidity IgG Testing for Differentiating of
      Toxoplasma gondii Infection in Early Stage of Pregnancy.
AB  - OBJECTIVE: Toxoplasma gondii infection, an intracellular parasite, is often
      asymptomatic or is caused by different clinical diseases without being detected.
      Evaluation of IgG, IgA, and IgM in order to diagnose the pending Toxoplasmosis
      may confront some problems. Several researches has showned that Toxo IgG avidity
      can be useful in the recent active Toxoplasmosis. In current study, modification
      and importance of improved Toxoplasma Avidity IgG testing has been evlauated for
      differentiating Toxoplasma gondii infection in early stage of pregnancy.
      MATERIALS AND METHODS: This experimental study included 300 pregnant women with
      risk of Toxoplasmosis in their initial months of pregnancy. We randomly divided
      300 serum samples into A group (n=60) with high avidity and B group (n=40) with
      borderline avidity. The samples with Toxo IgG levels were classified to four
      subgroups. IgG avidity was evaluated by enzyme-linked immunosorbent assay (ELISA)
      method. RESULTS: The mean absorbance of 100 samples in two groups was calculated,
      and then, two dilutaion curves with plotted absorbance against dilution were
      drawn for each serum sample. The results of this study showed that in groups with
      different concentrations of toxo IgG, appropriate dilution of serum is suitable
      for testing of Avidity. Our findings revealed the subgroups of 1, 2, 3, and 4
      with serum dilutios of 1/3 , 1/6, 1/9, and 1/18 respectively, had real and good
      avidity. CONCLUSION: : One of the issues affectig the results of avidity is high
      concenteration of Toxo IgG in serum sample. As shown in this study, the best
      points of dilution for well avidity in both high and borderline avidities are
      marked with arrows in figures 1-8. This study confirmed that improved methods of
      measuring Toxo Avidity IgG are very important.

PMID- 24027666
TI  - The effect of propolis as a biological storage media on periodontal ligament cell
      survival in an avulsed tooth: an in vitro study.
AB  - OBJECTIVE: Both the length of extra-alveolar time and type of storage media are
      significant factors that can affect the long-term prognosis of replanted teeth.
      This study aims to compare propolis 50%, propolis 10%, Hank's balanced salt
      solution (HBSS), milk and egg white on periodontal ligament (PDL) cell survival
      for different time points. MATERIALS AND METHODS: : In this in vitro experimental
      study, we divided 60 extracted teeth without any periodontal diseases into five
      experimental and two control groups that consisted each experimental group with
      10 and each control group with 5 teeth. The storage times were one and three
      hours for each media. The controls corresponded to 0-minute (positive) and 12
      hour (negative) dry time. Rinsing in the experimental media, the teeth were
      treated with dispase and collagenase for one hour. Cell viability was determined
      by using trypan blue exclusion. Statistical analysis of the data was accomplished
      by using two-way analysis of variance (ANOVA) complemented by the Tukey's HSD
      post-hoc. RESULTS: Within one hour, there was no significant difference between
      the two propolis groups, however these two groups had significantly more viable
      PDL cells compared to the other experimental media (p<0.05). The results of the
      three-hour group showed that propolis 10% was significantly better than egg
      white, whereas both propolis 10% and 50% were significantly better than milk
      (p<0.05). CONCLUSION: Based on PDL cell viability, propolis could be recommended
      as a suitable biological storage media for avulsed teeth.

PMID- 24027667
TI  - A novel in vitro model for cancer stem cell culture using ectopically expressed
      piwil2 stable cell line.
AB  - OBJECTIVE: Piwil2, a member of Ago/Piwi gene family containing Piwi and PAZ
      domains, has been shown to be ectopically expressed in different cancer cells,
      especially its remarkable expression in cancer stem cells (CSCs), and is also
      known to be essential for germ line stem cell self-renewal in various organisms.
      The hypothesis that CSC may hold the key to the central problem of clinical
      oncology and tumor relapse leads to more anticancer treatment studies. Due to
      emerging controversies and extreme difficulties in studying of CSC, like the
      cells using in vivo models, more attempts have expended to establish different in
      vitro models. However, the progress was slow owing to the problems associated
      with establishing proper CSC cultures in vitro. To overcome these difficulties,
      we prompted to establish a novel stable cell line over-expressing Piwil2 to
      develop a potential proper in vitro CSC model. MATERIALS AND METHODS: In this
      experimental study, mouse embryonic fibroblasts (MEFs) were isolated and
      electroporated with a construct containing Piwil2 cDNA under the control of the
      cytomegalovirus promoter (CMV). Stable transfectants were selected, and the
      established MEF-Piwil2 cell line was characterized and designated as CSC-like
      cells using molecular markers. Functional assays, including proliferation,
      migration, and invasion assays were performed using characterized CSC like cells
      in serum-free medium. Additionally, MEF-Piwil2 cell density and viability were
      measured by direct and indirect methods in normoxic and hypoxic conditions.
      RESULTS: The results of reverse transcriptase-polymerase chain reaction (RT-PCR),
      western blot, and immunocytochemistry revealed an overexpression for Piwil2 in
      the transfected Piwil2 cells both in the RNA and protein levels. Furthermore,
      analysis of the kinetic and stoichiometric parameters demonstrated that the
      specific growth rate and the yield of lactate per glucose were significantly
      higher in the MEF-Piwil2 group compared to the MEF cells (ANOVA, p< 0.05). Also,
      analysis of functional assays including migration and invasion assays
      demonstrated a significantly higher number of migrated and invaded cells in the
      MEF-Piwil2 compared to that of the MEF cells (ANOVA, p< 0.05). The MEF-Piwil2
      cells tolerated hypoxia mimetic conditions (CoCl2 ) with more than 95% viability.
      CONCLUSION: According to the molecular and functional studies, it has been
      realized that Piwil2 plays a key role(s) in tumor initiation, progression and
      metastasis. Therefore, Piwil2 can be used not only as a common biomarker for
      tumor, but also as a target for the development of new anticancer drug. Finally,
      the main outcome of our study was the establishment of a novel CSC-like in vitro
      model which is expected to be utilized in understanding the complex roles played
      by CSC in tumor maintenance, metastasis, therapy resistance or cancer relapse.

PMID- 24027668
TI  - Pattern of chromosomal aberrations in patients from north East iran.
AB  - OBJECTIVE: Chromosomal aberrations are common causes of multiple anomaly
      syndromes. Recurrent chromosomal aberrations have been identified by conventional
      cytogenetic methods used widely as one of the most important clinical diagnostic
      techniques. MATERIALS AND METHODS: In this retrospective study, the incidences of
      chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in
      Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and
      other cities in Khorasan province. Karyotyping was performed on 3728 patients
      suspected of having chromosomal abnormalities. RESULTS: The frequencies of the
      different types of chromosomal abnormalities were determined, and the relative
      frequencies were calculated in each group. Among these patients, 83.3% had normal
      karyotypes with no aberrations. The overall incidences of chromosomal
      abnormalities were 16.7% including sex and autosomal chromosomal anomalies. Of
      those, 75.1 % showed autosomal chromosomal aberrations. Down syndrome (DS) was
      the most prevalent autosomal aberration in the patients (77.1%). Pericentric
      inversion of chromosome 9 was seen in 5% of patients. This inversion was
      prevalent in patients with recurrent spontaneous abortion (RSA). Sex chromosomal
      aberrations were observed in 24.9% of abnormal patients of which 61% had Turner's
      syndrome and 33.5% had Klinefelter's syndrome. CONCLUSION: According to the
      current study, the pattern of chromosomal aberrations in North East of Iran
      demonstrates the importance of cytogenetic evaluation in patients who show
      clinical abnormalities. These findings provide a reason for preparing a local
      cytogenetic data bank to enhance genetic counseling of families who require this
      service.

PMID- 24027669
TI  - Osteogenic inhibition in multiple myeloma.
AB  - OBJECTIVE: Multiple myeloma (MM) is a plasma cell malignancy where plasma cells
      are increased in the bone marrow (BM) and usually do not enter peripheral blood,
      but produce harmful factors creating problems in these patients (e.g. malignant
      plasma cells over activate osteoclasts and inhibit osteoblasts with factors like
      RANKL and DKK). These factors are a main cause of bone lesion in MM patients.
      Recently SOST gene which responsible to encodes the sclerostin protein was
      identify. This protein specifically inhibits Wnt signaling in osteoblasts
      (inhibition of osteoblast differentiation and proliferation) and decrease bone
      formation and can also cause bone lesion in MM patients. MATERIALS AND METHODS:
      In this experimental study, human myeloma cell lines (U266 b1) were purchased
      from Pasteur Institute of Iran. Samples consisted of BM aspirates from the iliac
      crest of MM patients. BM with more than 70% plasma cell were selected for our
      study (6 patients) and one healthy donor. RNA extraction was done with Qiagen
      kit. was undertaken on mRNA of samples and cell lines. Also we purchased
      unrestricted somatic stem cells from Bonyakhte Company to evaluate the effect of
      soluble factors from myeloma cell lines on osteogenic differentiation medium.
      RESULTS: Our results showed that SOST is expressed significantly in primary
      myeloma cells derived from MM patients and myeloma cell lines. In other words,
      patients with more bone problems, express SOST in their plasma cells at a higher
      level. In addition, myeloma cells inhibit osteoblast differentiation in
      progenitor cells from umbilical cord blood stem cell (UCSC) in osteogenic
      inducing medium. CONCLUSION: There are many osteoblast maturation inhibitory
      factors such as DKK, Sfrp and Sclerostin that inhibit maturation of osteoblast in
      bone. Among osteoblast inhibitory agents (DKK, Sfrp, Sclerostin) sclerostin has
      the highest specificity and therefore will have less side effect versus non
      specific inhibitory agents. Our results also show that based on SOST expression
      in MM, there is a potential to inhibit sclerostin with antibody or alternative
      methods and prevent bone lesion in MM patients with the least side effect.

PMID- 24027670
TI  - Comment on: Anti-Oxidative Stress Activity of Stachys lavandulifolia Aqueous
      Extract in Humans.
AB  - A recent article by Rahzani et al. (1) published in the esteemed Cell Journal
      reported the antioxidative stress activity of Stachys lavandulifolia aqueous
      extract in humans and suggested its consumption as a supplement in the management
      of diseases related to oxidative stress. We would like to emphasize some of the
      limitations regarding antioxidant supplementation, in general, and Stachys
      lavandulifolia, in particular. It has been established that oxidative stress is
      involved in the development of a wide variety of chronic and degenerative
      diseases such as cancer, Parkinson and Alzheimer's (2-5). Antioxidants are also
      effective in the prevention or reduction of adverse effects related to medication
      usage (5-10). However, they may potentially have deleterious effects. A major
      concern of antioxidant supplementation is their harmful effect on reactive oxygen
      species (ROS) production (prooxidant action), particularly when precise
      modulation of ROS levels are necessary for normal cell function (4-10). In fact,
      it has been reported that antioxidants may exhibit pro-oxidant activity under
      specific conditions. Of particular importance are redox conditions the dosage and
      the presence of free transition metals at cellular sites. For example, the
      antioxidant vitamin C in the presence of ferric iron may act as a potent mediator
      of lipid peroxidation. It has been suggested that beta-carotene sometimes acts as
      a pro-oxidant in the lungs of smokers and similarly vitamin C may increase DNA
      damage in humans (11, 12). Therefore, it is necessary to take into account the
      bioavailability and differential activities of antioxidant compounds before their
      administration. Other than general considerations for antioxidant consumption,
      the aspects of each particular antioxidant should also be considered (3, 13, 14).
      Recently, in a preclinical study we reported the renal toxicity of hydroalcoholic
      extract of Stachys lavandulifolia Vahl in Wistar rats (15). In this experimental
      study we randomly assigned 100 male Wistar rats to five equal groups, one control
      and four experimental. Animals received intraperitoneal injections of saline or
      Stachys lavandulifolia extract (50, 100, 150, 200 mg/kg) for one month after
      which blood samples were collected from half of the animals from each group.
      Other animals received no injections for one additional month, then blood samples
      were obtained. In the groups that Stachys lavandulifolia Vahl extracts were used
      for one month we observed mild degeneration of renal tubular epithelial cells (6,
      9). In the second month of the study these histologic lesions significantly
      increased (p< 0.05). We concluded that hydroalcoholic extract of Stachys
      lavandulifolia has renal tubular toxicity which might continue following drug
      discontinuation (6, 9, 15). Therefore, although antioxidant supplements generally
      have beneficial effects, as a caution it is advised to only consume such
      supplements under medical supervision in order to avoid any potential negative
      effects. 

PMID- 24027672
TI  - Current evidence linking polyunsaturated Fatty acids with cancer risk and
      progression.
AB  - There is increasing evidence that polyunsaturated fatty acids (PUFAs) play a role
      in cancer risk and progression. The n-3 family of PUFAs includes alpha-linolenic
      acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) while the
      n-6 family includes linolenic acid (LA) and arachidonic acid (AA). EPA and DHA
      are precursors for anti-inflammatory lipid mediators while AA is a precursor for
      pro-inflammatory lipid mediators. Collectively, PUFAs play crucial roles in
      maintaining cellular homeostasis, and perturbations in dietary intake or PUFA
      metabolism could result in cellular dysfunction and contribute to cancer risk and
      progression. Epidemiologic studies provide an inconsistent picture of the
      associations between dietary PUFAs and cancer. This discrepancy may reflect the
      difficulties in collecting accurate dietary data; however, it also may reflect
      genetic variation in PUFA metabolism which has been shown to modify physiological
      levels of PUFAs and cancer risk. Also, host-specific mutations as a result of
      cellular transformation could modify metabolism of PUFAs in the target-tissue.
      Clinical trials have shown that supplementation with PUFAs or foods high in PUFAs
      can affect markers of inflammation, immune function, tumor biology, and
      prognosis. Pre-clinical investigations have begun to elucidate how PUFAs may
      mediate cell proliferation, apoptosis and angiogenesis, and the signaling
      pathways involved in these processes. The purpose of this review is to summarize
      the current evidence linking PUFAs and their metabolites with cancer and the
      molecular mechanisms that underlie this association. Identifying the molecular
      mechanism(s) through which PUFAs affect cancer risk and progression will provide
      an opportunity to pursue focused dietary interventions that could translate into
      the development of personalized diets for cancer control. 

PMID- 24027671
TI  - State-of-the-Art Research on "Lymphomas: Role of Molecular Imaging for Staging,
      Prognostic Evaluation, and Treatment Response".
AB  - Lymphomas are heterogeneous but potentially curable group of neoplasms. Treatment
      of lymphomas has rapidly evolved overtime with significant improvement in the
      cure rate and reductions in treatment-related toxicities. Despite excellent
      results, treatment programs are continued to be developed to achieve better
      curative and safety profiles. In these patients individualized therapy schemes
      can be devised based on a well-defined risk categorization. The therapy efficacy
      can be increased early during therapy in non-responding patients with escalated
      therapy protocols or with the addition of radiation therapy, particularly, in
      advanced-stage or unfavorable risk patients. The increasing availability of
      positron emission tomography using 18F-fluorodeoxyglucose, particularly fused
      with computed tomography (FDG-PET/CT) has lead to the integration of this
      modality into the routine staging and restaging for lymphoma with convincing
      evidence that it is a more accurate imaging modality compared with conventional
      imaging techniques. FDG-PET/CT is also is a promising surrogate for tumor
      chemosensitivity early during therapy. This review will summarize published data
      on the utility of FDG-PET/CT imaging in the staging, restaging, and predicting
      therapy response in patients with lymphoma. 

PMID- 24027673
TI  - Fluid restriction and prophylactic indomethacin in extremely low birth weight
      infants.
AB  - Although survival of extremely low birth weight (ELBW) infants dramatically
      improved over last decades, bronchopulmonary dysplasia (BPD) rate has not
      changed. The use of indomethacin prophylaxis in ELBW infants results in improved
      short-term outcomes with no effect on long-term outcomes. The addition of fluid
      restriction to the indomethacin prophylaxis policy could result in a reduction of
      BPD and improve long-term survival without neurosensory impairment at 18 months
      corrected age. To determine the effect of a policy of fluid restriction compared
      with a policy of no fluid restriction on morbidity and mortality in ELBW infants
      receiving indomethacin prophylaxis. The standard search strategy for the Cochrane
      Neonatal Review Group was used. This included search of OVID MEDLINE-National
      Library of Medicine, EMBASE, and the Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library, Issue 8, 2011). Additional search included
      conference proceedings, references in articles, and unpublished data. All
      randomized or quasi-randomized trials that compared fluid restriction and
      indomethacin prophylaxis vs. indomethacin prophylaxis alone in ELBW infants were
      included. Standard methods of the Cochrane Neonatal Review Group were planned to
      assess the methodological quality of the trials. Review Manager 5 software was
      planned to be used for statistical analysis. We found no randomized controlled
      trials to investigate the possible interaction between fluid restriction and
      indomethacin prophylaxis vs. indomethacin prophylaxis alone in ELBW infants. A
      well-designed randomized trial is needed to address this question. 

PMID- 24027675
TI  - Early CPAP versus Surfactant in Extremely Preterm Infants.

PMID- 24027674
TI  - Aborting a malformed fetus: a debatable issue in saudi arabia.
AB  - Congenital anomalies contribute a significant proportion of infant morbidity and
      mortality, as well as fetal mortality. They are generally grouped into three
      major categories: structural/metabolic, congenital infections, and other
      conditions. The most prevalent conditions include congenital heart defects,
      orofacial clefts, Down syndrome, and neural tube defects. Several prenatal
      diagnostic procedures have been introduced, both cytogenetic (such as chorion
      biopsy, amniocentesis and funiculocentesis) and biophysical (ultrasound 2-D, 3-D
      and 4-D, ultrasonography with Doppler, etc.). Insufficient data are currently
      available from Saudi Arabia on the epidemiology of the lethal congenital
      abnormalities which should be a priority due to high rate of consanguineous
      marriages among first cousins and their association with congenital anomalies. In
      terms of consanguinity and birth defects, a significant positive association has
      been consistently demonstrated between consanguinity and morbidity, and
      congenital defects with a complex etiology appear to be both more prevalent in
      consanguineous families and have a greater likelihood of recurrence. A debate
      regarding aborting a malformed fetus still exists among the senior Islamic
      scholars in many of the Islamic countries. The progressive interpretations of
      Islam have resulted in laws allowing for early abortion on request in two
      countries; six others permit abortion on health grounds and three more also allow
      abortion in cases of rape or fetal impairment. In Saudi Arabia, efforts to
      legalize abortion in certain circumstances have been recently discussed among
      Senior Religious Scholars and specialized physicians to permit abortions in
      certain circumstances. In this mini-review we discuss the current debate
      regarding aborting a malformed fetus in Saudi Arabia with a focus on the Islamic
      perspective.

PMID- 24027676
TI  - Antenatal magnesium sulfate decreases risk of cerebral palsy.

PMID- 24027677
TI  - Whole Body Hypothermia, Using Low Cost technique, is Safe and Effective in Term
      and Near-Term babies with Moderate and Severe Hypoxic Ischemic Encephalopathy.

PMID- 24027678
TI  - Bovine Lactoferrin Supplementation for Prevention of Late-onset Sepsis in very
      Low-Birth-Weight Neonates.

PMID- 24027679
TI  - Volume-targeted versus Pressure-limited Ventilation for Preterm Infants: A
      Systematic Review and Meta-Analysis.

PMID- 24027680
TI  - Impact of Nurse-Regulated Feedings on Growth Velocity and Weight Gain of 1200
      1500 g Preterm Infants.
AB  - PURPOSE: To evaluate the impact of nurse-regulated feedings (NRFs) on growth
      velocity and weight gain of 1200-1500 g preterm infants. SUBJECTS: Cohort 1: All
      preterm infants 1200-1500 g between 1997 and 2001 not on NRF protocol; Cohort 2:
      All preterm infants 1200-1500 g between 2003 and 2006 on NRF protocol. Both
      cohorts screened out for small gestation age, major congenital anomalies,
      intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), culture
      positive infection at birth, meningitis, and those requiring surgery. MATERIALS
      AND METHODS: A before and after matched cohort study was conducted in the years
      1997-2001 and 2003-2006, enrolling infants from Covenants Neonatal Intensive Care
      unit (Level III) using these studies screening protocol. Data on first 62
      enrolling infants from both cohorts were used for this study. Both cohorts were
      matched using gestational age, birth weight, length of stay, initial length. A
      modified data tool collection set was used for collecting and analyzing
      nutritional data, this included intake (cal/kg/d, cc/kg/d, and total intake in
      cc) and route (initial parenteral feedings, mixed parenteral and enteral
      feedings, full enteral feedings), NRF, and non-NRF (NNRF). Data collection
      continued until discharge, initiation of adlib feeding, or greater than 50% of
      nutrition from breast. DISCUSSION: Of the entire population sampled from 1997 to
      2006, there were only 59 for NRF and 58 for NNRF. The mean growth velocity
      (g/kg/d) to reach full enteral feedings for both cohorts was insignificant
      (t=0.233; P=0.816). This suggested both groups were well matched up to the point
      of NRF institution for the 2003-2006 cohort years. RESULTS: NRF had a 71% greater
      growth velocity than NNRF (P<0.001, t=6.618) at the time of discharge, initiation
      of adlib feeding, or greater than 50% of nutrition from breast. CONCLUSIONS: This
      study demonstrated that the NRF protocol offers a significant advantage in
      nutritional support than previous feeding regimens in this institution.

PMID- 24027681
TI  - Improvements in Birth Weight-specific Neonatal Mortality Rates in the State of
      Qatar between 2003 & 2010 and a Comparative Analysis with the Vermont Oxford
      Network Database Report of 2007: A PEARL Study Review.
AB  - OBJECTIVE: The study aimed to develop a national reference on birth weight
      specific neonatal survival in the State of Qatar to facilitate parental
      counseling. STUDY DESIGN: This was a retrospective, analytic, and comparative
      study. MATERIALS AND METHODS: The birth weight-specific neonatal mortality data
      for the years 2003 and 2010, collected from the admission and discharge registers
      of the neonatal intensive care unit, were stratified using the stratifications
      given in Vermont Oxford Network (VON) 2007 annual report. Category-wise birth
      weight-specific mortality and relative risk (RR) of death were compared between
      Qatar data (2003 and 2010) and VON 2007 report. RESULTS: Qatar's neonatal
      mortality rate (NMR) dropped from 5 of 1000 in 2003 to 4.4 of 1000 in 2010
      (P=0.443) which was significant for birth weight categories 501-750 g and 751
      1000 g (P=0.026 and P=0.05, respectively). Qatar's NMR in 2010 was significantly
      lower than VON's NMR during 2007 (P<0.001) though VON's NMR was significantly
      lower among birth weight categories 751-1000 g and 1001-1500 g (P=0.001 and
      P=0.003, respectively). The RR of mortality decreased with increasing birth
      weight. The decline was very sharp for birth weight categories between 500 and
      1500g. The RR was 25 times higher in babies with birth weight less than 750 g as
      compared to babies with birth weight >= 2550 g, both in Qatar and VON data. For
      birth weight categories 751-1000 g and 1001-1500 g, the RR was twice in Qatar as
      compared to the VON report (16.8 versus 7.8, and 5.5 versus 2.7, respectively).
      CONCLUSIONS: Qatar's current overall and birth weight-specific NMRs are
      comparable with the VON report except in birth weight categories 751-1000 g and
      1001-1500 g which were higher in Qatar. This needs further in-depth qualitative
      analysis.

PMID- 24027682
TI  - Neonatal short-term outcomes of gestational diabetes mellitus in saudi mothers: a
      retrospective cohort study.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) affects up to 10% of all
      pregnancies and results in significant maternal and neonatal morbidities.
      OBJECTIVES: Our main objective was to investigate retrospectively the rate of
      neonatal intensive care unit (NICU) admissions and significant neonatal
      complications in pregnant mothers with gestational diabetes. MATERIALS AND
      METHODS: A retrospective cohort study was conducted. The medical records of King
      Khalid University Hospital (KKUH) were reviewed from January till December 2007.
      All pregnant women with GDM along with their offsprings were included and matched
      with healthy pregnant women. The primary outcome was the rate of NICU admission,
      hypoglycemia, birth weight and length of hospital stay. RESULTS: A total of 766
      mothers (419 GDM mothers and 347 controls) with their term babies were included.
      Infants born to GDM mothers had significantly higher risk of NICU admissions [OR
      2.7 (95% CI 1.5, 4.9), P value 0.0004], longer hospital stay and higher rates of
      hypoglycemia. Newborns of GDM mothers had higher rates of perinatal distress and
      macrosomia; however, the difference did not reach statistical significance.
      CONCLUSION: GDM remains a significant morbidity to newborns resulting in
      increased intensive care admission, prolongation of hospital stay and higher
      rates of neonatal hypoglycemia. More efforts to assure early recognition and
      strict sugar control during pregnancy are still needed.

PMID- 24027683
TI  - Outcome of exchange blood transfusions done for neonatal jaundice in abakaliki,
      South eastern Nigeria.
AB  - BACKGROUND: Neonatal jaundice (NNJ) is a major cause of morbidity and mortality
      among neonates in Nigeria and exchange blood transfusion (EBT) is a common
      modality of its treatment in Ebonyi State University Teaching Hospital (EBSUTH),
      Abakaliki. This communication aims to audit this service. MATERIALS AND METHODS:
      A 3-year retrospective review of the case files of all neonates that had EBT for
      NNJ at the new born special care unit of EBSUTH. RESULT: Two hundred and thirty
      seven (17.25%) out of 1374 neonatal admissions had NNJ. EBT was performed for 40
      (16.9%) of them. The commonest indications for EBT were low birth
      weight/prematurity, ABO blood group incompatibility, sepsis and glucose 6
      phosphate deficiencies. The mean serum bilirubin at which EBT was done was 28.3
      mg/dl. The EBT was uneventful in 36 cases while in four (10%) cases there were
      reported adverse events. Seven neonates (17.5%) died after the procedure and
      documented causes of death include bilirubin encephalopathy, respiratory failure,
      and septic shock and disseminated intravascular coagulopathy. CONCLUSION: There
      is high rate of EBT use in the management of severe neonatal hyperbilirubinemia
      with significant morbidity and mortality in this study site. There is need to
      review the contribution of factors such as late presentation in the hospital to
      this and proffer solutions to it.

PMID- 24027684
TI  - Jejunoileal Atresia: Factors Affecting the Outcome and Long-term Sequelae.
AB  - CONTEXT: Jejunoileal atresia (JIA) is a common abnormality. The outcome is
      conditioned by several variables. Nutritional problems, and long-term sequelae
      are described among those who survive. AIM: To correlate the type of JIA and its
      management to the outcome and long-term quality of life. SETTINGS AND DESIGN:
      Forty-three cases over a 17-year period (1992-2009). Perinatal data, management,
      and outcome were extracted from the clinical notes. The cases that had survived
      were contacted to get information about their present condition. MATERIALS AND
      METHODS: Morbidity and mortality were matched to maturity, birth weight, mode of
      diagnosis, type of JIA, associated anomalies, and management and duration of
      parenteral nutrition. Growth and quality of life in 34 cases were evaluated via a
      telephone interview at a minimum of one year from surgery. STATISTICAL ANALYSIS:
      Fisher test, Linear regression test, Kruskal-Wallis test, Dunn's comparison test.
      RESULTS: Male/Female ratio was 25/18 and median birth weight was 2.644 g.
      Prenatal diagnosis was recorded in 34%. Six patients (14%) had associated
      anomalies. Primary surgery was resection and anastomosis in 88% and temporary
      stoma in 12%. Length of the resected bowel ranged from 3 to 65 cm. Whenever
      multiple atresia was found, the bowel length was saved by multiple anastomosis.
      Three dehiscences and three adhesive obstructions required a reoperation. Two
      patients (4%) died due to a central catheter-related sepsis. Prenatal diagnosis
      did not influence the outcome and was associated with a higher rate of Cesarean
      deliveries. Interview, at a median of nine years, showed normal growth in 85%.
      One case of short bowel syndrome is still on parenteral support at 22 months.
      CONCLUSIONS: Preserving bowel length and reducing the recourse to stoma is the
      key to good outcome and growth. Sequelae are correlated with the type of atresia
      and length of residual bowel; however, they decrease their severity with time.

PMID- 24027685
TI  - Umbilical Myiasis Associated with Staphylococcus Aureus Sepsis in a neonate.
AB  - Myiasis is an infection of live mammalian tissue by the larvae of dipteran flies
      and commonly found in the tropics and subtropics. It usually infects domestic and
      wild animals, but sometimes also affects human. Umbilical cord myiasis in the
      neonatal period associated with sepsis is a rare occurrence with few reported
      cases in the literature. In this article, authors report a 7-day-old neonate from
      a rural area presented with neonatal sepsis due to umbilical myiasis caused by
      fly larval form of blow fly (Chrysomya megacephala). 

PMID- 24027686
TI  - Bilateral humerus fracture following birth trauma.
AB  - Birth injuries especially to humerus are rare in Caesarean sections as compared
      to vaginal deliveries. But in some difficult extractions even with expert care,
      injury may be sustained by the newborn. This is a report of a case of birth
      trauma induced fractures of both humerus during Caesarean section. 

PMID- 24027687
TI  - A case of antley-bixler syndrome.
AB  - Antley-Bixler syndrome (ABS) is rare form of craniosynostosis of both autosomal
      dominant and autosomal recessive inheritance. We are reporting a female term
      appropriate for gestational age newborn with clinical features of frontal
      bossing, brachycephaly, proptosis, synostosis of radioulnar joints, hemangioma
      over nose and philtrum, hydrocephalus suggestive of ABS. 

PMID- 24027688
TI  - Prune Belly Syndrome Associated with Full Spectrum of VACTERL in a New Born.
AB  - Prune belly syndrome (PBS) is a rare congenital anomaly of uncertain etiology.
      Many associations of PBS with other malformations were previously reported, but
      only few cases of the association with VACTERL have been described. We report a
      rare case of a Moroccan new born with PBS and complete VACTERL association. The
      cause of this association is still unknown, but a common etiology is possible,
      especially when for the two syndromes, a defect in mesodermal differentiation, in
      early first trimester, has been suggested. 

PMID- 24027690
TI  - Survival without Disability to Age 5 years After Neonatal Caffeine Therapy for
      Apnea of Prematurity.

PMID- 24027689
TI  - Guidelines for Rational and Cost-Effective Use of iNO Therapy in Term and Preterm
      Infants.
AB  - Inhaled nitric oxide (iNO) is an effective but costly therapy for infants with
      hypoxemic respiratory failure. The approved and solidly evidence-based indication
      is for treatment of late preterm and term infants with persistent pulmonary
      hypertension of the newborn (PPHN); however, off-label use of iNO has become
      widespread. Although iNO treatment of infants with congenital diaphragmatic
      hernia constitutes one of the approved indications, available evidence from
      randomized trials suggests marginal if any efficacy. Rescue therapy in preterm
      infants with severe respiratory failure has been studied extensively and is not
      supported by data from a number of controlled trials. Such use is widespread, but
      should be discouraged. There may be a subgroup of such infants with pulmonary
      hypoplasia and documented PPHN who may benefit from this treatment, but the data
      are limited. Several studies have examined the use of iNO for prevention of
      chronic lung disease with inconsistent results. This promising application
      requires more study before it can be recommended. There may be a role of iNO in
      treating infants with pulmonary hypertension complicating severe bronchopulmonary
      dysplasia, but there are limited data on long term outcomes. Alternate therapies
      such as sildenafil may be beneficial in this specific population as well as in
      other causes of pulmonary hypertension. Rational use of this expensive treatment
      will maximize cost:benefit and avoid potential exposure to unknown adverse
      effects not balanced by documentable benefits. 

PMID- 24027691
TI  - Preliminary evaluation of a new technique of minimally invasive surfactant
      therapy.

PMID- 24027692
TI  - Bovine lactoferrin prevents invasive fungal infections in very low birth weight
      infants: a randomized controlled trial.

PMID- 24027693
TI  - Inhaled nitric oxide in preterm infants undergoing mechanical ventilation.

PMID- 24027694
TI  - Neonatal sepsis: high antibiotic resistance of the bacterial pathogens in a
      neonatal intensive care unit of a tertiary care hospital.
AB  - OBJECTIVE: To study the bacterial pathogens causing neonatal sepsis and their
      sensitivity pattern so that guidelines can be prepared for empirical antibiotic
      therapy. MATERIALS AND METHODS: We conducted a prospective analysis of all the
      cases admitted to the neonatal intensive care unit (NICU) of a tertiary care
      hospital and studied the culture and sensitivity pattern of organisms isolated.
      The neonates who presented with signs and symptoms of septicemia, with/without
      pneumonia and/or meningitis were studied and a detailed record of the maturity,
      age at onset, sex, birth weight (weight on admission for home deliveries),
      symptoms and signs along with the maternal risk factors was made. The cases with
      suspect sepsis were screened using various screening markers. Blood culture was
      done in all the cases, while cerebrospinal fluid was analysed only in those
      indicated. Sensitivity of the isolated organism was tested by Kirby Bauer disc
      diffusion techniques and various drug resistance mechanisms were studied. RESULT:
      Out of the 190 neonates (M:F=1.22:1) admitted to the NICU, 60 (31.57%) shows
      blood culture positive. Ninety-five percent cases were due to early onset
      septicemia. Thirty one neonates had Gram negative, twenty seven had Gram positive
      septicemia and two had candidial infection. Seventy percent Gram-positive
      isolates were resistant to penicillin. Ninety percent Gram negative isolates were
      resistant to gentamycin and ampicillin. Carbapenem resistance mechanisms such as
      ESBL. CONCLUSION: There is an increasing trend of antibiotic resistance to the
      commonly used and available drugs. Continuous surveillance for antibiotic
      susceptibility should be done to look for resistance pattern.

PMID- 24027695
TI  - Retinopathy of Prematurity: A Study of Incidence and Risk Factors in NICU of Al
      Minya University Hospital in Egypt.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a serious complication of
      prematurity treatment and can lead to blindness unless recognized and treated
      early. OBJECTIVE: To estimate the incidence of ROP in preterm infants in our
      NICU, to identify the risk factors which predispose to ROP, and to assess the
      outcome of these cases. MATERIALS AND METHODS: ROP prospective screening survey
      was performed enrolling all prematures admitted to the NICU from January 2009 to
      December 2010, with a gestational age of 32 weeks or less at birth and a birth
      weight of 1500 g or less. Infants whom gestational age was >32 weeks or birth
      weight was >1500 g were included if they exposed to oxygen therapy for more than
      7 days. Also infants who were born between 32 and 34 weeks gestational age were
      examined if they had a course of instability (like sepsis, asphyxia or
      ventilation). A total of 172 infants (88 females) had retinal evaluation by
      indirect ophthalmoscopy from the 4(th) postnatal week and followed up
      periodically. Perinatal risk factors for ROP were assessed using univariate and
      multivariate analysis. Infants who progressed to stage 3 ROP with plus disease
      were given laser therapy. RESULTS: Out of the studied 172 infants, 33 infants
      (19.2%) developed ROP in one or both eyes; 18 (54.5%) cases stage 1, 9 (27.3%)
      cases stage 2 and 6 (18.2%) cases stage 3 with plus disease. None of the studied
      neonates presented ROP at stages 4 or 5. The six cases diagnosed as ROP stage 3
      with plus disease underwent laser ablative therapy. Laser was effective in
      treatment and decreasing the progression of ROP. Univariate analysis showed that
      there was a significant relationship between the occurrence of ROP and
      gestational age (P=0.000), sepsis (P=0.004), oxygen therapy (P=0.018), and
      frequency of blood transfusions (P=0.030). However, nonsignificant relationship
      was found between the occurrence of ROP and sex, mode of delivery, birth weight,
      respiratory distress syndrome, patent ductus arteriosus, intraventricular
      hemorrhage, hypotension, phototherapy, duration of oxygen therapy, mechanical
      ventilation, and CPAP (all P>0.05). Gestational age, sepsis, oxygen therapy and
      frequency of blood transfusions remained significant variables after logistic
      regression analysis. CONCLUSION: The incidence of ROP in this study was 19.2%;
      low gestational age, sepsis, oxygen therapy and frequent blood transfusions were
      significant risk factors for ROP. Laser was effective in treatment and decreasing
      the progression of ROP. As this is a unit-based study, a comprehensive
      countrywide survey on ROP in Egypt is recommended to determine any regional
      differences in disease incidence.

PMID- 24027696
TI  - NT-proBNP Levels Improve the Ability of Predicting a Hemodynamically Significant
      Patent Ductus Arteriosus in Very Low-Birth-Weight Infants.
AB  - PURPOSE: A hemodynamically significant Patent ductus arteriosus (HsPDA) in
      premature infants is known to be associated with significant morbidity. Recently
      brain natriuretic peptides and superior mesenteric artery (SMA)-resistive indices
      have been used to effectively diagnose HsPDA. OBJECTIVE: To assess the
      sensitivity and specificity of N-terminal proBNP (NT-proBNP) in predicting an
      HsPDA diagnosed by clinical and echocardiographic criteria including pulsatility
      index (PI) of SMA. MATERIALS AND METHODS: All preterm neonates <1500 g were
      evaluated with echocardiograms and NT-proBNP levels on the 3(rd) to 5(th) day of
      life and then every week until the echo showed either a closed PDA or non-HsPDA.
      RESULTS: Sixty-nine babies with mean gestational age of 27 weeks were included in
      the study. NT-proBNP levels were significantly higher in the HsPDA group (n=22)
      with a mean+/-SEM of 24420+/-3190 compared to 3072+/-332 in the non-HsPDA group
      (n=47) (P<0.001). NT-pro BNP level of 5900 pg/ml had 96% sensitivity and 90%
      specificity of predicting HsPDA. CONCLUSIONS: With frequently changing
      hemodynamics in low-birth weight infants, including NT-proBNP and PI of SMA
      improve the ability of assessing the effects of a HsPDA and will help timing of
      intervention.

PMID- 24027697
TI  - Neonatal herpes simplex fulminant hepatitis successfully treated with acyclovir.
AB  - Disseminated neonatal herpes simplex virus (HSV) infection is characterized by
      progressive multiple organ failure and high mortality rates up to 85% for
      untreated neonates. It can result from infection with either HSV-1 or HSV-2. We
      report the first known case of disseminated neonatal herpes associated with
      fulminant liver failure caused by HSV-2 who survived without liver transplant. 

PMID- 24027698
TI  - Use of octeriotide in the management of neonatal chylothorax secondary to repair
      of congenital diaphragmatic hernia: a report of two cases and review of
      literature.
AB  - Chylothorax, a known complication of surgery for Congenital Diaphragmatic hernia,
      can sometimes be resistant to treat. Octeriotide (Somatostatin analogue) can be
      useful in this situation. However, the dose and schedule of Octeriotide therapy
      in neonates is not well established. We report two cases of resistant chylothorax
      following surgery for congenital diaphragmatic hernia which were successfully
      managed by using an escalating infusion of octeriotide. The literature on the
      subject is also reviewed. 

PMID- 24027699
TI  - Neonatal hepatitis with toxoplasmosis.
AB  - Congenital toxoplasmosis may be subclinical, or may present with multisystem
      involvement. Most of the symptomatic cases have either ocular or neurological
      manifestations. A case of congenital toxoplasmosis presenting as isolated
      hepatitis is reported. 

PMID- 24027700
TI  - Successful treatment of persistent hypoxemia by nasal suctioning in a neonate
      with primary ciliary dyskinesia.
AB  - Primary ciliary dyskinesia (PCD) is a genetic disorder that manifests clinically
      with chronic sinopulmonary and otologic disease. Despite the majority of patients
      presenting with respiratory symptoms in the neonatal period, the diagnosis is
      often delayed until several years of age. We report the case of a 5-day-old male
      who was diagnosed with PCD by electron microscopic evaluation of cilia obtained
      from nasal brush biopsy. This case also demonstrated the successful treatment of
      persistent hypoxemia with frequent nasal suctioning. 

PMID- 24027701
TI  - Whole body cooling for infants with hypoxic-ischemic encephalopathy.

PMID- 24027703
TI  - NIPPV after Surfactant Treatment for RDS Reduces the Need for Mechanical
      Ventilation at 7 Days of Age and BPD in Preterm Infants: Interpret Results with
      Caution.

PMID- 24027702
TI  - Oxidative stress and bronchopulmonary dysplasia.
AB  - Bronchopulmonary dysplasia (BPD) is the major cause of pulmonary disease in
      infants. The pathophysiology and management of BPD changed with the improvement
      of neonatal intensive care unit (NICU) management and with the increase of
      survival rates. Despite the improvements made, BPD is still a public health
      concern, resulting in frequent hospitalizations with high rates of mortality,
      impaired weight and height growth, and neurodevelopmental disorders. Lung injury
      in the neonatal period has multiple etiologic factors - genetic, hemodynamic,
      metabolic, nutritional, mechanical, and infectious mechanisms - act in a
      cumulative and synergic way. Free radical (FR) generation is largely recognized
      as the major cause of lung damage. Oxidative stress (OS) is the final common
      endpoint for a complex convergence of events, some genetically determined and
      some triggered by in utero stressors. Inflammatory placental disorders and
      chorioamnionitis also play an important role due to the coexistence of
      inflammatory and oxidative lesions. In addition, the contribution of airway
      inflammation has been extensively studied. The link between inflammation and OS
      injury involves the direct activation of inflammatory cells, especially
      granulocytes, which potentiates the inflammatory reaction. Individualized
      interventions to support ventilation, minimize oxygen exposure, minimize apnea,
      and encourage growth should decrease both the frequency and severity of BPD.
      Future perspectives suggest supplementation with enzymatic and/or non-enzymatic
      antioxidants. The use of antioxidants in preterm newborns particularly exposed to
      OS and at risk for BPD represents a logical strategy to ameliorate FRs injury,
      but further studies are needed to support this hypothesis. 

PMID- 24027704
TI  - When to treat hemodynamically insignificant patent ductus arteriosus in preterm
      infants.

PMID- 24027705
TI  - Nasal continuous positive airway pressure with heliox in preterm infants with
      respiratory distress syndrome.

PMID- 24027706
TI  - Elective high-frequency oscillatory ventilation versus conventional ventilation
      for acute pulmonary dysfunction in preterm infants.

PMID- 24027707
TI  - Trends in incidence of neonatal sepsis and antibiotic susceptibility of causative
      agents in two neonatal intensive care units in tehran, I.R iran.
AB  - BACKGROUND: Neonatal sepsis is a worldwide problem that presents a management
      challenge to care groups for neonates and infants. Early diagnosis and management
      can considerably decrease the risk of sepsis, and improve the outcome. AIM: The
      aim of the present study was to determine the incidence, causative pathogens, and
      the antibiotic sensitivity pattern for neonatal sepsis in Iran. MATERIALS AND
      METHODS: A historical cohort study was conducted on 84 patients with neonatal
      sepsis who were admitted to the neonatal intensive care unit (NICU) wards of
      Baqiyatallah and Najmieh University hospitals in Tehran, between 2003 and 2006.
      Clinical, demographic and laboratory data was collected from medical records.
      RESULTS: Among all the comprised neonates, 44 patients were diagnosed with early
      onset sepsis, 23 cases with late-onset sepsis and others with nosocomial sepsis.
      The most common isolated pathogen in all groups was Enterobacter, and was
      responsible for 31.4%, 47.8% and 41.2% of the episodes of sepsis, according to
      the sepsis type mentioned above, respectively. Susceptibility of common sepsis
      related pathogens to imipenem and gentamycin gradually reduced over the years
      between 2003 and 2006. Total mortality and morbidity rates due to neonatal sepsis
      were estimated at 27.4% and 89.3%, respectively. Mortality following sepsis was
      found more in boys (Odds Ratio (OR)=4.897, Conifdence Interval (CI)=95%,
      P=0.031), and those with low birth weight (OR=4.406, CI: 95%, P=0.011). Higher
      sepsis related co-morbidity was found in neonates following cesarean delivery
      (OR=6.280, CI: 95%, P=0.025). CONCLUSION: It seems that the mortality rate in
      this study was lower than similar studies in Iran and other developing countries.
      This difference between the mortality rates of the centers in our study and
      others could be due to the high occurrence of Enterobacter infections in the
      latter and also high resistance of these pathogens to commonly used antibiotics
      such as beta-lactams and aminoglycosides reported in other studies.

PMID- 24027708
TI  - Hypoxia as a predisposing factor for the development of early onset neonatal
      thrombocytopenia.
AB  - BACKGROUND: Thrombocytopenia in hypoxic neonates admitted in NICU is a morbid
      condition encountered very commonly. Early-onset thrombocytopenia (<72 h) is most
      commonly associated with fetomaternal conditions complicated by placental
      insufficiency and/or fetal hypoxia. Chronic intrauterine hypoxia is the most
      frequent cause of early-onset thrombocytopenia in preterm neonates. AIMS: In this
      study incidence and clinical impact of early thrombocytopenia in hypoxic neonates
      was investigated. SETTING AND DESIGN: Neonatal intensive care unit of a tertiary
      level hospital attached to a medical college in Central India. A cross-sectional,
      observational hospital based study in hypoxic neonates for development of
      thrombocytopenia. MATERIALS AND METHODS: 603 hypoxic newborns were evaluated for
      development of thrombocytopenia. 155 (25.07%) developed thrombocytopenia and were
      the cases. Non thrombocytopenic babies 448 (74.29%) served as controls. The two
      groups were compared for birth weight, sex ratio, gestational age, severity of
      asphyxia, platelet counts and mortality rate. STATISTICAL ANALYSIS: Descriptive
      statistics of continuous variable were expressed in mean and SD. P value less
      than or equal to 0.05 were statistically significant. RESULTS AND CONCLUSIONS: We
      found thrombocytopenia to be associated with male gender, prematurity and low
      birth weight. Most babies had mild to moderate thrombocytopenia. Mortality was
      higher in preterm thrombocytopenic babies as compared to term. We suggest
      screening for thrombocytopenia in all asphyxiated newborns, as hypoxia can lead
      to neonatal thrombocytopenia.

PMID- 24027709
TI  - Serum level of ghrelin in umbilical cord in small and appropriate for gestational
      age newborn infants and its relationship to anthropometric measures.
AB  - OBJECTIVE: To compare the cord blood ghrelin level in (SGA) infants with the
      level in appropriate for gestational age (AGA) infants, and determine its
      relationship to anthropometric measurements at delivery. MATERIALS AND METHODS:
      Fifty newborn infants (30 SGA newborns and 20 AGA infants) were included in the
      study and were subjected to complete clinical examinations, anthropometric
      measurement, and ghrelin assays. RESULTS: The cord blood ghrelin level in SGA
      infants was significantly higher than that in AGA infants. Cord ghrelin level
      correlated negatively with gestational age, weight, length, and body mass index
      in SGA group. CONCLUSION: Cord ghrelin concentration increased in SGA infants due
      to state of prolonged undernutrition the source of ghrelin unknown may be from
      the mother placenta or fetal tissues.

PMID- 24027710
TI  - Effects of phototherapy on cytokines' levels and white blood cells in term
      neonate with hyperbilirubinemia.
AB  - OBJECTIVE: Phototherapy is the most common treatment used for severe jaundice.
      There is increasing evidence that phototherapy can directly affect the expression
      and function of cell surface receptors including adhesion molecules, cytokines,
      and growth factor receptors. The aim of this study is to investigate the effect
      of phototherapy use on the levels of interleukin (IL)-1alpha, IL-6, and tumor
      necrosis factor (TNF)-alpha as cytokine expressions from keratinocytes, and also
      white blood cell counts in the treatment of neonate with hyperbilirubinemia.
      MATERIALS AND METHODS: We studied 32 term newborns with hyperbilirubinemia. Blood
      samples were obtained before and 72 h after phototherapy. Serum levels of IL
      1alpha, IL-6, TNF-alpha, and WBC count were measured in the samples using
      appropriate methods. RESULTS: Serum TNF-alpha at 72 h of exposure to phototherapy
      increased, while the levels of IL-1alpha and IL-6 at the same time were
      decreased. These changes were not statistically significant. WBC counts rose
      significantly with phototherapy. CONCLUSION: Phototherapy in term neonate does
      not affect cytokines' levels, but can raise peripheral WBC count.

PMID- 24027711
TI  - Linear nevus sebaceous syndrome in a neonate conceived by intracytoplasmic sperm
      injection.
AB  - Linear nevus sebaceous syndrome is a multisystem disorder including nevus
      sebaceous, which is the hallmark of this syndrome, together with central nervous
      system, ocular and skeletal anomalies. We report a case of extensive skin
      lesions, CNS and eye anomalies in a full term infant who was conceived by
      intracytoplasmic sperm injection. 

PMID- 24027712
TI  - Sirenomelia apus: a rare deformity.
AB  - Sirenomelia also known as the mermaid syndrome, is a rare congenital malformation
      of uncertain etiology. It is characterized by fusion of the lower limbs and
      commonly associated with severe urogenital and gastrointestinal malformations.
      There are approximately 300 cases reported in the literature, 15% of which are
      associated with twinning, most often monozygotic. The syndrome of caudal
      regression is thought to be the result of injury to the caudal mesoderm early in
      gestation. 

PMID- 24027713
TI  - Mediastinal enteric cyst in a neonate.
AB  - Mediastinal enteric cysts are relatively uncommon, and patients tend to present
      at a later age compared to those with duplications in other areas of alimentary
      canal. The tendency of enteric cyst to enlarge and produce airway obstruction is
      sufficient reason for early surgical removal. We report on a case of mediastinal
      enteric cyst in a neonate with respiratory distress for its early presentation
      and management. The embryological basis and anatomical issues relating to
      duplication cysts of the gastrointestinal tract is discussed. 

PMID- 24027714
TI  - A severe and rapidly progressive case of proteus syndrome in a neonate who
      presented with unilateral hydrocephalus apart from other typical features of the
      proteus syndrome.
AB  - Proteus syndrome is a rare hamartomatous disorder affecting multiple tissues and
      manifesting itself in a variety of ways. The understanding of the complete
      spectrum of clinical features, the natural clinical course of the disease and the
      proper management of such a rare but highly variable syndrome depend heavily on
      experiences gathered by previously reported cases. We present an unusually
      severely affected and rapidly progressive case of proteus syndrome in a neonate
      who presented with craniofacial hemihypertrophy, subcutaneous masses, capillary
      hemangioma, varicose veins, epidermal nevi and macrodactyly. The cranial
      ultrasonogram revealed unilateral hydrocephalus with partial obstruction of the
      foramen of monro. 

PMID- 24027715
TI  - Congenital chikungunya.
AB  - Chikungunya virus (CHIKV) infection manifesting in neonates is very rare. The
      prevalence of the entity was described only recently. We describe a neonate with
      chikungunya who presented with severe thrombocytopenia and features of multisytem
      involvement. Identification of this entity based on clinical and epidemiological
      background helps in appropriate management and aids in prognostication of the
      affected neonate. 

PMID- 24027716
TI  - Potter's Sequence.
AB  - Potter's sequence is a rare fatal disorder that occurs in sporadic and autosomal
      recessive forms with an incidence of 1 in 4000 births. Babies born with this
      condition are either still born or die very early within the neonatal period. We
      report a case of Potter's sequence with the typical physical findings and
      histological findings. 

PMID- 24027717
TI  - Klippel - trenaunay - weber syndrome.
AB  - 7 days old baby was admitted in Kamla Raja Raja Hospital with complaints of
      swelling on upper limb and lower limb. Polydactly of fingers and toes were
      present. All systems were normal Lab investigation - Blood examination was normal
      Ultrasound of abdomen, Echocardiography and CT scan of brain - Normal. 

PMID- 24027718
TI  - Healthcare-associated Sepsis in the Neonatal Intensive Care Unit: A Practical
      Approach.

PMID- 24027719
TI  - Ectopia cordis.
AB  - Ectopia cordis is a rare congenital anomaly. Congenital anomaly scan can detect
      it at 18-23 weeks of gestation. Four chamber view of the heart in routine fetal
      anomaly scans at >18 weeks is the most effective technique to detect CHD
      prenatally. 

PMID- 24027720
TI  - Role of levetiracetam in neonatal seizure.

PMID- 24027721
TI  - Is sildenafil an effective therapy in the management of persistent pulmonary
      hypertension?
AB  - Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening
      neonatal pathology resulting from poor hemodynamic and respiratory transition to
      extra uterine life. Inhaled nitric oxide (iNO) is a current, commonly used
      treatment of PPHN. However, iNO is not available therapy in many developing
      countries and around 50% of infants with PPHN do not respond to iNO therapy.
      Sildenafil is a phosphodiesterase inhibitor type 5 (PDE5) that has been shown to
      selectively reduce pulmonary vascular resistance in both animal models and adult
      humans. Recent studies have found that in PPHN, administration of Sildenafil was
      associated with a significant increase in the oxygenation and a reduction in
      mortality with no clinically important side effects. 

PMID- 24027722
TI  - Methods of Weaning Preterm Babies <30 weeks Off CPAP: A Multicenter Randomized
      Controlled Trial.

PMID- 24027723
TI  - Chemoprophylaxis of neonatal fungal infections in very low birth weight infants:
      efficacy and safety of fluconazole and nystatin.

PMID- 24027724
TI  - Benefits of iron supplementation for low birth weight infants.

PMID- 24027725
TI  - Early or delayed enteral feeding for preterm growth-restricted infants: a
      randomized trial.

PMID- 24027726
TI  - A PEARL Study Analysis of National Neonatal, Early Neonatal, Late Neonatal, and
      Corrected Neonatal Mortality Rates in the State of Qatar during 2011: A
      Comparison with World Health Statistics 2011 and Qatar's Historic Data over a
      Period of 36 Years (1975-2011).
AB  - OBJECTIVE: To prospectively ascertain Qatar's national Neonatal Mortality Rate
      (NMR), Early Neonatal Mortality Rate (ENMR), and Late Neonatal Mortality Rate
      (LNMR) during 2011, compare it with recent data from high-income countries, and
      analyze trends in Qatar's NMR's between 1975 and 2011 using historic data. STUDY
      DESIGN: A National prospective cohort-study. MATERIALS AND METHODS: National data
      on live births and neonatal mortality was collected from all public and private
      maternity facilities in Qatar (1(st) January-December 31(st) 2011) and compared
      with historical neonatal mortality data (1975-2010) ascertained from the database
      of maternity and neonatal units of Women's Hospital and annual reports of Hamad
      Medical Corporation. For inter country comparison, country data of 2009 was
      extracted from World Health Statistics 2011 (WHO) and the European Perinatal
      Health report (2008). RESULTS: A total of 20583 live births were recorded during
      the study period. Qatar's national NMR during 2011 was 4.95, ENMR 2.7, LNMR 2.2,
      and cNMR 3.33. Between 1975 and 2011, Qatar's population increased by 10-fold,
      number of deliveries by 7.2 folds while relative risk of NMR decreased by 87% (RR
      0.13, 95% CI 0.10-0.18, P<0.001), ENMR by 91% (RR 0.09, 95% CI 0.06-0.12,
      P<0.001) and LNMR by 58% (RR 0.42, 95% CI 0.23-0.74, P=0.002). The comparable
      ranges of neonatal mortality rates from selected high-income West European
      countries are: NMR: 2-5.7, ENMR 1.5-3.8, and LNMR 0.5-1.9. CONCLUSIONS: The
      neonatal survival in the State of Qatar has significantly improved between 1975
      and 2011. The improvement has been more marked in ENMR than LNMR. Qatar's current
      neonatal mortality rates are comparable to most high-income West European
      countries. An in-depth research to assess the correlates and determinants of
      neonatal mortality in Qatar is indicated.

PMID- 24027727
TI  - Granulocyte Colony-stimulating Factor for Preterms with Sepsis and Neutropenia: A
      Randomized Controlled Trial.
AB  - BACKGROUND: Bacterial sepsis is one of the major causes of mortality in newborn
      infants. Mortality increases when sepsis is associated with neutropenia.
      MATERIALS AND METHODS: We conducted a prospective, randomized, double-blind,
      placebo-controlled trial of recombinant human granulocyte colony-stimulating
      factor on preterm neonates (gestational age (GA) <34 weeks) with sepsis and
      absolute neutrophil count (ANC) of <1500 cells/mm(3). Mortality, duration of
      Neonatal Intensive Care Unit (NICU) stay, hematological parameters (ANC, platelet
      count, and total leukocyte count) were compared between the two groups. The GCSF
      group (n=39) received GCSF intravenously in a single daily dose of 10 MUg/kg/day
      in a 5% dextrose solution over 20-40 min for three consecutive days, while the
      control group (n=39) received placebo of an equivalent volume of 5% dextrose.
      RESULTS: Baseline demographic profile among the two groups was comparable.
      Mortality rate in the GCSF group was significantly lower than in the control
      group (10% vs. 35%; P<0.05). By day 3 of treatment, ANC in the GCSF group was
      significantly higher (3521+/-327) compared to 2094+/-460 in the control group,
      with P value being <0.05. Duration of NICU stay also decreased significantly in
      the GCSF group. CONCLUSION: The administration of GCSF in preterms with
      septicemia and neutropenia resulted in lower mortality rates. Further studies are
      required to confirm our results and establish this adjunctive therapy in neonatal
      sepsis.

PMID- 24027728
TI  - Neonatal mastitis: controversies in management.
AB  - OBJECTIVE: To document the range of presentations, extent of investigations, and
      treatment choices of 'physicians treating' neonates with mastitis seen over a 9
      year period at a tertiary care pediatric hospital. MATERIALS AND METHODS: An
      email survey was sent to Emergency Department (ED) staff and fellows asking them
      how they would treat a well-looking neonate with localized mastitis. Secondly, a
      retrospective chart review of neonates presenting to the ED with a diagnosis of
      neonatal mastitis or breast engorgement from July 2000 to December 2009 was
      conducted to assess how such patients were actually treated. RESULTS: 46/107
      surveys were returned, with a wide discrepancy in how clinicians would treat
      neonatal mastitis: 4.3% would perform a full sepsis work up, including lumbar
      puncture, followed by IV antibiotics and hospital admission; 28% chose discharge
      on oral antibiotics; and 28% suggested admission only if blood work was abnormal.
      From the chart review, 33 neonates were diagnosed with possible neonatal mastitis
      over a 9-year period: 12 met the inclusion criteria. Of these, 8 (66%) were
      admitted and treated with intravenous antibiotics, 2 (16.6%) were treated with
      oral antibiotics, and 2 (16.6%) did not receive antibiotics. None of the 12
      patients had lumbar puncture performed. CONCLUSION: There is significant
      disagreement among clinicians regarding the best way to treat the well-looking
      neonate with localized mastitis. Most elect to perform blood tests and start
      treatment with IV antibiotics with good Staphylococcus aureus coverage, followed
      by oral antibiotics if cultures are negative.

PMID- 24027729
TI  - Neonatal mesenchymal hamartoma of liver: an unusual presentation.
AB  - Mesenchymal hamartoma of the liver is the second most common benign liver tumor
      in children. Typically, it presents as a large benign cystic, solid or mixed
      liver mass in a child younger than 3 years and amenable to complete resection. We
      report a neonate with Mesenchymal hamartoma of the liver presenting as giant
      intra abdominal cyst and its rare association with malrotation of bowel. 

PMID- 24027730
TI  - Congenital Neurofibromatosis in a Saudi Neonate who Presented with Neck Mass,
      Esophageal and Airway Obstruction.
AB  - We are presenting a case of a neonate presented with a neck mass, airway and
      esophageal obstruction, the tumor has a brain extension; treated with partial
      surgical excision; the pathological studies revealed plexiform Neurofibromatosis.
      The patient also has cafe au lait spots. 

PMID- 24027731
TI  - Gastroschisis associated with lower limb and spinal congenital anomalies.
AB  - Gastroschisis is not a very rare congenital deformity, but extragastrointestinal
      association is rare, if any present, in that condition, an alternative diagnosis
      should be considered, like Pentalogy of Cantrell, Limb-body wall complex, etc.,
      Other birth defects are always associated with gastroschisis, most commonly,
      abnormalities of the cardiac and genitourinary. The present case is one of the
      gastroschisis to highlight the associations of spinal and lower limbs anomalies,
      with two-vessel short umbilical cord and severe oligohydramnios in primiparous. 

PMID- 24027732
TI  - Sirenomelia: a rare case of foetal congenital anomaly.
AB  - Sirenomelia, alternatively known as 'mermaid syndrome' is a very rare congenital
      deformity in which the legs are fused together, giving them the appearance of the
      tail of a mermaid'. Other birth defects are always associated with sirenomelia,
      most commonly abnormalities of the kidneys, large intestines, and genitalia. The
      present case is a one of sirenomelia associated with an absent right kidney, mild
      left hydronephrosis, single umbilical artery, and severe oligohydramnios. We
      discuss the findings, relative to the present literature and related
      etiopathogenesis. 

PMID- 24027733
TI  - Pseudohypoaldosteronism type 1: a rare cause of severe dyselectrolytemia and
      cardiovascular collapse in neonates.
AB  - Severe hyperkalemia is a medical emergency and occurs due to a variety of
      underlying illnesses. We present a 7 day old neonate who presented with life
      threatening hyperkalemia due to pseudohypoaldosteronism type 1 (PHA1). The
      clinical picture resembled congenital adrenal hyperplasia (CAH). Very aggressive
      management including peritoneal dialysis was required to control hyperkalemia. It
      is important to differentiate PHA1 from CAH since the former does not respond to
      corticosteroid therapy and may require peritoneal dialysis for control of
      hyperkalemia. A discussion on the types, clinical course, and management of
      pseudohypoaldosteronism type 1 is presented. 

PMID- 24027734
TI  - Monozygotic twins with trisomy 13 presenting with variable phenotype.

PMID- 24027736
TI  - Erythropoietin may improve the Outcome in Infants with Moderate to Severe Hypoxic
      Ischemic Encephalopathy.

PMID- 24027737
TI  - Probiotics for the management of infantile colic in breastfed infants.

PMID- 24027735
TI  - Stem cell therapy for neonatal diseases associated with preterm birth.
AB  - In the last decades, the prevention and treatment of neonatal respiratory
      distress syndrome with antenatal steroids and surfactant replacement allowed the
      survival of infants born at extremely low gestational ages. These extremely
      preterm infants are highly vulnerable to the detrimental effects of oxidative
      stress and infection, and are prone to develop lung and brain diseases that
      eventually evolve in severe sequelae: The so-called new bronchopulmonary
      dysplasia (BPD) and the noncystic, diffuse form of periventricular leukomalacia
      (PVL). Tissue simplification and developmental arrest (larger and fewer alveoli
      and hypomyelination in the lungs and brain, respectively) appears to be the
      hallmark of these emerging sequelae, while fibrosis is usually mild and
      contributes to a lesser extent to their pathogenesis. New data suggest that loss
      of stem/progenitor cell populations in the developing brain and lungs may
      underlie tissue simplification. These observations constitute the basis for the
      application of stem cell-based protocols following extremely preterm birth.
      Transplantation of different cell types (including, but not limited to,
      mesenchymal stromal cells, endothelial progenitor cells, human amnion epithelial
      cells) could be beneficial in preterm infants for the prevention and/or treatment
      of BPD, PVL and other major sequelae of prematurity. However, before this new
      knowledge can be translated into clinical practice, several issues still need to
      be addressed in preclinical in vitro and in vivo models. 

PMID- 24027738
TI  - Feeding Intolerance in Preterm Infants Fed with Powdered or Liquid Formula: A
      Randomized Controlled, Double-blind Pilot Study.

PMID- 24027739
TI  - Neonatal visits to the pediatric emergency center and its implications on
      postnatal discharge practices in qatar.
AB  - BACKGROUND: An early discharge from postnatal policy has been practiced at
      Women's Hospital, Hamad Medical Corporation. AIM: This observational cohort study
      was conducted to evaluate the effect of early postnatal discharge practice on
      neonatal morbidity in the State of Qatar. SETTING AND DESIGN: This is a data
      based cohort study. All neonates <=28 days visiting the Pediatric Emergency
      Centers (PEC) were evaluated for the need for re-hospitalization, referral for
      clinic appointments, or observation at the PEC setting. MATERIALS AND METHODS:
      Differences in outcome rates were compared in neonates who visited in the first
      24 hours postnatal discharge (2-3 days of life) and those who visited after the
      third day of life. STATISTICAL ANALYSIS: Crude differences in incidence rate
      assessed by chi(2) or Fisher exact test were applicable. RESULTS: Of 3528 PEC
      visits for 1915 neonates, 1.7% required admission (3.1% of neonates), 8.4% were
      observed, 1.1% were referred to a clinic, and the remaining were discharged home.
      There was no significant difference in re-hospitalization rates of neonates
      visiting PEC in the first 3 days and those visiting at a later age (OR 0.78, 95%
      CL 0.19-3.23, P=1). However, early presentations to PEC was more likely to result
      in periods of observation (OR 1.88, 95% CL 1.17-3.04, P=0.01), or clinic referral
      (OR 4.96, 95% CL 2.16-11.38, P=0.001) when compared to older neonates. Moreover,
      those who presented early were significantly more likely to revisit any of the
      PECs with in the 28 days period (OR 3.20, 95% CL 2.17-4.97, P<0.0001).
      CONCLUSION: These results clearly demonstrate the need for a structured early
      post-discharge follow-up service that addresses the needs of all neonates and
      their families. The results, however, do not provide sufficient evidence that
      delaying postnatal discharges for apparently healthy neonates will provide
      significant health benefits to these neonates and their families.

PMID- 24027740
TI  - Correlation of pulse oximetry and apgar scoring in the normal newborns.
AB  - CONTEXT: Apgar score (AS) is routinely used for assessment of newborns
      immediately after birth. Within acceptable limits, low saturations at birth are
      normal in vigorous newborn babies. Various studies have questioned the
      reliability of AS. AIMS: To detect whether AS is an accurate indicator of
      hypoxemia and to study the correlation of different components of AS with the
      arterial oxygenation saturation (SpO2) levels of normal newborns in the delivery
      room. SETTINGS AND DESIGN: A prospective cross-sectional observational study on
      normal healthy neonates delivered vaginally in a tertiary level referral medical
      college. MATERIALS AND METHODS: SpO2 levels were monitored continuously in the
      newborns with a pulse oximeter and serial recording of SpO2 levels was done at 5
      min intervals starting at 1 min of life until 30 min after birth. Simultaneously,
      AS was recorded in these newborns at 1 and 5 min of life. STATISTICAL ANALYSIS:
      Data was analyzed using the Mann-Whitney-U test. RESULTS: AS at 1 and 5 min of
      life didn't correlate with the changes in SpO2 of newborns. In AS; though
      respiratory efforts and muscle tone were significantly correlated with SpO2 of
      the newborns, body color did not have significant correlation with simultaneously
      recorded SpO2. CONCLUSIONS: A revised AS in which evaluation of color is replaced
      by pulse oximetry monitoring would prove to be a better tool for neonatal
      evaluation in the immediate postnatal period.

PMID- 24027741
TI  - Performance evaluation of hematologic scoring system in early diagnosis of
      neonatal sepsis.
AB  - OBJECTIVES: The present study was undertaken to evaluate and highlight the
      importance of hematological scoring system (HSS) in the early detection of
      neonatal sepsis. MATERIALS AND METHODS: The cross-sectional study enrolled 110
      neonates who were clinically suspected of infection (study group) and normal
      neonates for comparison (controls), during the 1(st) week of life. All peripheral
      blood smears were analyzed using HSS of Rodwell et al., by pathologists blinded
      to the infection status of the newborns. HSS assigns a score of 1 for each of
      seven findings significantly associated with sepsis: Abnormal total leukocyte
      count, abnormal total polymorphonuclear neutrophils (PMN) count, elevated
      immature PMN count, elevated immature: Total (I:T) PMN ratio, immature: Mature
      (I:M) PMN ratio >=0.3, platelet count <=150,000/mm(3), and pronounced
      degenerative or toxic changes in PMNs. Score of <=2 was interpreted as sepsis
      unlikely; score 3-4: Sepsis is possible and >=5 sepsis or infection is very
      likely. Blood culture was taken as a standard indicator for septicemia. The
      perinatal history, clinical profile and laboratory data were recorded and
      correlated in each case. Each hematological parameter was assessed for its
      individual performance and also with the culture-proven sepsis. Sensitivity,
      specificity, positive and negative predictive values (NPVs) were calculated for
      each parameter and for different gestational ages. P value was also calculated
      for different parameters. RESULTS: Out of the 110 infants, based on clinical
      findings and laboratory data were classified into three categories: Sepsis
      (n=42), probable infection (n=22) and normal (n=46). Out of these, 42 (38.2%)
      newborns had positive blood culture. 63 (57%) neonates were preterm and 47 (43%)
      term. Male: female ratio was 0.96:1. The P value was significant for the
      different gestational ages (0.0002) and sex ratio (0.003). Immature
      polymorphonuclear neutrophils (PMN) count was the most sensitive and I:M PMN
      ratio, the most specific indicator of sepsis. For sepsis and probable sepsis, I:T
      PMN count and immature PMN count have highest sensitivity whereas I:T and I:M PMN
      ratio have highest specificity. HSS has much higher sensitivity and specificity
      in preterms than in term neonates. Positive predictive value and NPV is also
      higher in preterm than term for HSS. It was also seen that with increasing
      scores, the likelihood of sepsis also increased. CONCLUSION: The sensitivities of
      the various screening parameters were found to be satisfactory in identifying
      early onset neonatal sepsis. It is a simple and feasible diagnostic tool to guide
      towards the decision-making for a rationale treatment.

PMID- 24027742
TI  - An Interesting Observation of PDA Closure with Oral Paracetamol in Preterm
      Neonates.
AB  - Patent ductus arteriosus (PDA), in which there is a persistent communication
      between the descending thoracic aorta and the pulmonary artery that results from
      failure of normal physiologic closure of the fetal ductus, is one of the more
      common congenital heart defects in preterm neonates. The closure of PDA can be
      done with either Indomethacin or Brufen which are cyclooxygenase 1, 2 inhibitor;
      however these drugs are associated with side effects. We report an interesting
      findings of ductal closure in 10 preterm neonates (gestational age 27-33 wks)
      presenting with significant large PDA who had failed or had absolute
      contraindication with Brufen. These preterm neonates were treated with oral
      paracetamol in the dose of 15 mg/kg 8 hourly. The PDA closure was achieved within
      48 h and there was no complication. 

PMID- 24027743
TI  - Congenital giant hydronephrosis: a rare cause for upper abdominal mass in the
      newborn.
AB  - We report a rare case of antenatally detected unilateral pelvi-ureteric junction
      obstruction leading to congenital giant hydronephrosis presenting as upper
      abdominal mass at birth. 

PMID- 24027744
TI  - Neck swelling in a newborn with congenital goiter.
AB  - Congenital goiter presenting in the newborn period is very rare. We present a
      case of primary hypothyroidism presenting as congenital goiter in the newborn
      period with symptoms in the immediate postnatal life. Hormone replacement therapy
      was started leading to normal levels of free thyroxine and triiodothyronine. In
      face of maternal normal thyroid levels, dysharmonogenesis was considered to be
      the most probable cause of hypothyroidism. 

PMID- 24027745
TI  - A Rare Case of Pyridoxine-dependent Seizures in Infancy.
AB  - Pyridoxine-dependent seizures is a rare cause of recurrent seizures in neonatal
      period and resistant to most of the antiepileptic medications, but respond to
      administration of pyridoxine. We report a male infant who had neonatal seizures
      which were initially responsive to anticonvulsants and later became unresponsive
      and presented at 45 days of life with seizures. These seizures were not
      responding to any anticonvulsant but responded to pyridoxine. After discharge
      parents inadvertently stopped pyridoxine and the infant presented with seizures
      once again. These seizures were promptly controlled with readministration of
      pyridoxine confirming the diagnosis of pyridoxine-dependant seizures. 

PMID- 24027746
TI  - A huge immature cervical teratoma; antenatal diagnosis, and its management - an
      unusual entity.
AB  - Cervical teratomas are not reported quite frequently in medical literature,
      especially from Indian subcontinent. Prenatal diagnosis of this condition is even
      rarer, making the management protocols difficult. In absence of prompt
      intervention in the form of airway decompression, morbidity and mortality is very
      high. Presented here is the case of antenatal diagnosed cervical mass, which was
      managed successfully in immediate post-natal period with uneventful survival and
      normalized tumor marker levels. 

PMID- 24027747
TI  - A Saudi Patient with an Interstitial Deletion of Short Arm of Chromosome 3 (p13
      to p21) and its Association with Joubert's Syndrome Features.
AB  - We report a case of 4 weeks old girl with a de novo interstitial deletion of the
      short arm of chromosome 3 (p13-p21) and clinical findings typical of proximal 3p
      deletion together with heart defects, choanal atresia, ear anomalies, central
      nervous system anomalies, renal anomalies and associated Joubert's syndrome (JS).
      Family history is unremarkable and parenteral chromosomes were normal. The
      clinical manifestations of the patient are compared with those of 11 patients
      previously described with a proximal 3p deletion. The additional JS features
      associated with this syndrome were described. This is the first case report in
      English literature describing 3p deletion associated with additional JS features.

PMID- 24027748
TI  - Chilaiditi syndrome: a rare manifestation in newborn.
AB  - 1 days newborn presents with abdominal distention, excessive cry, respiratory
      distress and off fed, abdominal - distended, tenders, tympanic and bowel sound
      high present were present. Chest X-ray - Gas between below the right colic angle
      between liver and right diaphragm. Treatment - Conservatives. 

PMID- 24027749
TI  - Mortality rate of one neonatal intensive care unit in tehran, iran.

PMID- 24027750
TI  - Interferon-alpha enhances 5'-deoxy-5-fluorouridine-induced apoptosis by ERK
      dependant upregulation of thymidine phosphorylase.
AB  - 5-Florouracil (5-FU) is the basic agent used in the treatment of gastric cancer.
      Capecitabine, a prodrug of 5-FU, displays increased antitumor efficacy compared
      with 5-FU in the clinic. 5'-Deoxy-5-fluorouracil (5'-DFUR), the metabolite of
      capecitabine, is converted to 5-FU by the enzyme thymidine phosphorylase (TP),
      which is present at high concentrations in human tumors. In this study, we
      investigated the effect of interferon-alpha (IFN-alpha) on the sensitivity of
      gastric cancer cells to treatment with 5'-DFUR and its relationship with TP
      expression. Preincubation of gastric cancer cells with IFN-alpha enhanced 5'-DFUR
      induced apoptosis via IFN-alpha-mediated upregulation of TP. The depletion of TP
      with small interfering RNA (siRNA) obviously inhibited IFN-alpha-induced
      upregulation of TP expression and thus prevented apoptosis induced by IFN-alpha
      and 5'-DFUR. Treatment with IFN-alpha and combined IFN-alpha and 5'-DFUR
      treatment were also associated with concomitant activation of ERK signaling.
      Treatment with the ERK inhibitor PD98059 or depletion of ERK with siRNA partially
      reversed IFN-alpha-induced upregulation of TP expression, thus partially
      preventing apoptosis induced by IFN-alpha and 5'-DFUR. Taken together, our study
      shows that IFN-alpha enhanced 5'-DFUR-induced apoptosis in gastric cancer cells
      by upregulation of TP expression, which is partially regulated by activation of
      ERK signaling.

PMID- 24027751
TI  - Treatment of slaughter house wastewater in a sequencing batch reactor:
      performance evaluation and biodegradation kinetics.
AB  - Slaughterhouse wastewater contains diluted blood, protein, fat, and suspended
      solids, as a result the organic and nutrient concentration in this wastewater is
      vary high and the residues are partially solubilized, leading to a highly
      contaminating effect in riverbeds and other water bodies if the same is let off
      untreated. The performance of a laboratory-scale Sequencing Batch Reactor (SBR)
      has been investigated in aerobic-anoxic sequential mode for simultaneous removal
      of organic carbon and nitrogen from slaughterhouse wastewater. The reactor was
      operated under three different variations of aerobic-anoxic sequence, namely,
      (4+4), (5+3), and (3+5) hr. of total react period with two different sets of
      influent soluble COD (SCOD) and ammonia nitrogen (NH4(+)-N) level 1000 +/- 50
      mg/L, and 90 +/- 10 mg/L, 1000 +/- 50 mg/L and 180 +/- 10 mg/L, respectively. It
      was observed that from 86 to 95% of SCOD removal is accomplished at the end of
      8.0 hr of total react period. In case of (4+4) aerobic-anoxic operating cycle, a
      reasonable degree of nitrification 90.12 and 74.75% corresponding to initial
      NH4(+)-N value of 96.58 and 176.85 mg/L, respectively, were achieved. The
      biokinetic coefficients (k, K(s), Y, k(d)) were also determined for performance
      evaluation of SBR for scaling full-scale reactor in future operation.

PMID- 24027752
TI  - LPS increases MUC5AC by TACE/TGF-alpha/EGFR pathway in human intrahepatic biliary
      epithelial cell.
AB  - BACKGROUND: Mucin 5AC (MUC5AC) overproduction plays important roles in stone
      formation and recurrence of hepatolithiasis. We aim to investigate the involved
      mechanism and the potential target to block this process. METHODS: 42 bile duct
      samples from hepatolithiasis and 15 normal bile duct samples from hemangioma
      patients were collected for detecting MUC5AC expression by immunohistochemistry.
      MUC5AC and phosphoepidermal growth factor receptor (pEGFR) expressions in human
      intrahepatic biliary epithelial cells (HIBECs) cultured with or without
      lipopolysaccharide (LPS) were detected by real-time PCR and western blot
      analysis. Transforming growth factor-alpha (TGF-alpha) secretion in HIBECs was
      detected by ELISA. RESULTS: MUC5AC was overexpressed in bile ducts of
      hepatolithiasis samples compared with bile ducts from hemangioma samples. LPS
      upregulated MUC5AC expression in HIBECs. LPS promoted EGFR activation, and
      inhibiting EGFR activation by AG1478 significantly decreased LPS-induced MUC5AC
      overexpression in HIBECs. Moreover, LPS increased TGF-alpha secretion, and
      inhibiting tumor necrosis factor-alpha converting enzyme (TACE), which has been
      implicated in ectodomain cleavage of TGF-alpha, significantly inhibited LPS
      induced EGFR activation and subsequent MUC5AC overexpression in HIBECs.
      CONCLUSION: Our results suggested that LPS increases MUC5AC expression through
      the TACE/TGF-alpha/EGFR pathway in HIBECs. This new finding might give light to
      the prevention of stone formation and recurrence of hepatolithiasis.

PMID- 24027753
TI  - SubMito-PSPCP: predicting protein submitochondrial locations by hybridizing
      positional specific physicochemical properties with pseudoamino acid
      compositions.
AB  - Knowing the submitochondrial location of a mitochondrial protein is an important
      step in understanding its function. We developed a new method for predicting
      protein submitochondrial locations by introducing a new concept: positional
      specific physicochemical properties. With the framework of general form
      pseudoamino acid compositions, our method used only about 100 features to
      represent protein sequences, which is much simpler than the existing methods. On
      the dataset of SubMito, our method achieved over 93% overall accuracy, with
      98.60% for inner membrane, 93.90% for matrix, and 70.70% for outer membrane,
      which are comparable to all state-of-the-art methods. As our method can be used
      as a general method to upgrade all pseudoamino-acid-composition-based methods, it
      should be very useful in future studies. We implement our method as an online
      service: SubMito-PSPCP. 

PMID- 24027754
TI  - Congenital and acquired abnormalities of the corpus callosum: a pictorial essay.
AB  - The purpose of this review is to illustrate the wide spectrum of lesions in the
      corpus callosum, both congenital and acquired: developmental abnormalities,
      phakomatoses, neurometabolic disorders, demyelinating diseases, infection and
      inflammation, vascular lesions, neoplasms, traumatic and iatrogenic injury, and
      others. Cases include fetuses, children, and adults with rich iconography from
      the authors' own archive.

PMID- 24027755
TI  - An in vitro evaluation of antioxidant and colonic microbial profile levels
      following mushroom consumption.
AB  - The biological activity of mushroom consumption is achieved by the antioxidant
      effect of constituent biomolecules released during digestion. In the following
      study, the consumption of mushroom fungi was determined to increase the number of
      Lactobacillus and Bifidobacterium strains within the colon. The main phenolic
      antioxidant compounds identified were both gentisic and homogentisic acids.
      Moreover, the flavonoid catechin as well as a significant amount of delta - and
      gamma-tocopherols was determined. The amount of Lactobacillus and Bifidobacterium
      strains from different sections of the human colon was significantly correlated
      with levels of antioxidative biomolecules. The experimental data clearly
      demonstrate a significant impact of mushroom consumption on the fermentative
      function of microorganisms in the human colon, resulting in the homeostasis of
      normal physiological colonic functions.

PMID- 24027756
TI  - High-frequency transcutaneous peripheral nerve stimulation induces a higher
      increase of heat pain threshold in the cutaneous area of the stimulated nerve
      when confronted to the neighbouring areas.
AB  - BACKGROUND: TENS (transcutaneous electrical nerve stimulation) is probably the
      most diffused physical therapy used for antalgic purposes. Although it continues
      to be used by trial and error, correct targeting of paresthesias evoked by the
      electrical stimulation on the painful area is diffusely considered very important
      for pain relief. AIM: To investigate if TENS antalgic effect is higher in the
      cutaneous area of the stimulated nerve when confronted to neighbouring areas.
      METHODS: 10 volunteers (4 males, 6 females) underwent three different sessions:
      in two, heat pain thresholds (HPTs) were measured on the dorsal hand skin before,
      during and after electrical stimulation (100 Hz, 0.1 msec) of superficial radial
      nerve; in the third session HPTs, were measured without any stimulation. RESULTS:
      Radial nerve stimulation induced an increase of HPT significantly higher in its
      cutaneous territory when confronted to the neighbouring ulnar nerve territory,
      and antalgic effect persisted beyond the stimulation time. CONCLUSIONS: The
      location of TENS electrodes is crucial for obtaining the strongest pain relief,
      and peripheral nerve trunk stimulation is advised whenever possible. Moreover,
      the present study indicates that continuous stimulation could be unnecessary,
      suggesting a strategy for avoiding the well-known tolerance-like effect of
      prolonged TENS application.

PMID- 24027757
TI  - Skeletal muscle oxygen saturation (StO2) measured by near-infrared spectroscopy
      in the critically ill patients.
AB  - According to current critical care management guidelines, the overall hemodynamic
      optimization process seeks to restore macrocirculatory oxygenation, pressure, and
      flow variables. However, there is increasing evidence demonstrating that, despite
      normalization of these global parameters, microcirculatory and regional perfusion
      alterations might occur, and persistence of these alterations has been associated
      with worse prognosis. Such observations have led to great interest in testing new
      technologies capable of evaluating the microcirculation. Near-infrared
      spectroscopy (NIRS) measures tissue oxygen saturation (StO2) and has been
      proposed as a noninvasive system for monitoring regional circulation. The present
      review aims to summarize the existing evidence on NIRS and its potential clinical
      utility in different scenarios of critically ill patients. 

PMID- 24027758
TI  - Composted versus raw olive mill waste as substrates for the production of
      medicinal mushrooms: an assessment of selected cultivation and quality
      parameters.
AB  - Two-phase olive mill waste (TPOMW, "alperujo") is a highly biotoxic sludge-like
      effluent of the olive-oil milling process with a huge seasonal production. One of
      the treatment approaches that has so far received little attention is the use of
      TPOMW as substrate for the cultivation of edible mushrooms. Fifteen fungal
      strains belonging to five species (Basidiomycota), that is, Agrocybe cylindracea,
      Pleurotus cystidiosus, P. eryngii, P. ostreatus, and P. pulmonarius, were
      evaluated for their efficacy to colonize media composed of TPOMW, which was used
      either raw or composted in mixtures with wheat straw in various ratios. Qualified
      strains exhibited high values of biological efficiency (e.g., 120-135% for
      Pleurotus spp. and 125% for A. cylindracea) and productivity in subsequent
      cultivation experiments on substrates supplemented with 20-40% composted TPOMW or
      20% raw TPOMW. Only when supplementation exceeded 60% for raw TPOMW, a negative
      impact was noted on mushroom yields which could be attributed to the effluent's
      toxicity (otherwise alleviated in the respective composted TPOMW medium).
      Earliness and mushroom size as well as quality parameters such as total phenolic
      content and antioxidant activity did not demonstrate significant differences
      versus the control wheat-straw substrate. The substrates hemicellulose content
      was negatively correlated with mycelium growth rates and yields and positively
      with earliness; in addition, cellulose: lignin ratio presented a positive
      correlation with mycelium growth and mushroom weight for A. cylindracea and with
      earliness for all species examined. TPOMW-based media revealed a great potential
      for the substitution of traditional cultivation substrates by valorizing
      environmentally hazardous agricultural waste. 

PMID- 24027759
TI  - Bioeffects of static magnetic fields: oxidative stress, genotoxic effects, and
      cancer studies.
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. Exposure to SMF can increase the activity,
      concentration, and life time of paramagnetic free radicals, which might cause
      oxidative stress, genetic mutation, and/or apoptosis. Current evidence suggests
      that cell proliferation can be influenced by a treatment with both SMFs and
      anticancer drugs. It has been recently found that SMFs can enhance the anticancer
      effect of chemotherapeutic drugs; this may provide a new strategy for cancer
      therapy. This review focuses on our own data and other data from the literature
      of SMFs bioeffects. Three main areas of investigation have been covered: free
      radical generation and oxidative stress, apoptosis and genotoxicity, and cancer.
      After an introduction on SMF classification and medical applications, the basic
      phenomena to understand the bioeffects are described. The scientific literature
      is summarized, integrated, and critically analyzed with the help of authoritative
      reviews by recognized experts; international safety guidelines are also cited. 

PMID- 24027761
TI  - An approach for identifying cytokines based on a novel ensemble classifier.
AB  - Biology is meaningful and important to identify cytokines and investigate their
      various functions and biochemical mechanisms. However, several issues remain,
      including the large scale of benchmark datasets, serious imbalance of data, and
      discovery of new gene families. In this paper, we employ the machine learning
      approach based on a novel ensemble classifier to predict cytokines. We directly
      selected amino acids sequences as research objects. First, we pretreated the
      benchmark data accurately. Next, we analyzed the physicochemical properties and
      distribution of whole amino acids and then extracted a group of 120-dimensional
      (120D) valid features to represent sequences. Third, in the view of the serious
      imbalance in benchmark datasets, we utilized a sampling approach based on the
      synthetic minority oversampling technique algorithm and K-means clustering
      undersampling algorithm to rebuild the training set. Finally, we built a library
      for dynamic selection and circulating combination based on clustering (LibD3C)
      and employed the new training set to realize cytokine classification. Experiments
      showed that the geometric mean of sensitivity and specificity obtained through
      our approach is as high as 93.3%, which proves that our approach is effective for
      identifying cytokines. 

PMID- 24027762
TI  - Polyphenolic contents and antioxidant properties of different grape (V. vinifera,
      V. labrusca, and V. hybrid) cultivars.
AB  - The polyphenolic contents and the antioxidant activity of the skins and pulps of
      different grape cultivars were estimated using HPLC and DPPH antioxidant assay,
      respectively. The phenolics and flavonoids identified were quercetin, kaempferol,
      caffeic acid, p-coumaric acid, cinnamic acid, and (-)-epicatechin. The total
      phenolic contents were found to be the highest in the grape skin of Flouxa (>400
      mg/100 g), followed by Campbell Early and Tamnara (>300 mg/100 g), and then by
      Red Globe and Ruby Seedless (>250 mg/100 g), and the total phenolic content was
      the lowest in Italia and Delaware (<60 mg/100 g). The antioxidant activities of
      the grape extracts varied from 12.5% (Ruby Seedless) to 60.2% (Hongiseul) for
      skins, whereas the antioxidant activities of the grape extracts varied from 35.4%
      (Campbell Early) to 84.5% (Hongiseul) for pulps. The grape pulps have stronger
      antioxidant activities than those of the grape skins. Our results suggest that
      the phenolic and flavonoid contents in extracts of grape skins and pulps showed
      statistically significant correlations with the free radical scavenging activity.

PMID- 24027760
TI  - Development of microencapsulation delivery system for long-term preservation of
      probiotics as biotherapeutics agent.
AB  - The administration of probiotic bacteria for health benefit has rapidly expanded
      in recent years, with a global market worth $32.6 billion predicted by 2014. The
      oral administration of most of the probiotics results in the lack of ability to
      survive in a high proportion of the harsh conditions of acidity and bile
      concentration commonly encountered in the gastrointestinal tract of humans.
      Providing probiotic living cells with a physical barrier against adverse
      environmental conditions is therefore an approach currently receiving
      considerable interest. Probiotic encapsulation technology has the potential to
      protect microorganisms and to deliver them into the gut. However, there are still
      many challenges to overcome with respect to the microencapsulation process and
      the conditions prevailing in the gut. This review focuses mainly on the
      methodological approach of probiotic encapsulation including biomaterials
      selection and choice of appropriate technology in detailed manner. 

PMID- 24027763
TI  - Knockout of Density-Enhanced Phosphatase-1 impairs cerebrovascular reserve
      capacity in an arteriogenesis model in mice.
AB  - Collateral growth, arteriogenesis, represents a proliferative mechanism involving
      endothelial cells, smooth muscle cells, and monocytes/macrophages. Here we
      investigated the role of Density-Enhanced Phosphatase-1 (DEP-1) in arteriogenesis
      in vivo, a protein-tyrosine-phosphatase that has controversially been discussed
      with regard to vascular cell biology. Wild-type C57BL/6 mice subjected to
      permanent left common carotid artery occlusion (CCAO) developed a significant
      diameter increase in distinct arteries of the circle of Willis, especially in the
      anterior cerebral artery. Analyzing the impact of loss of DEP-1 function,
      induction of collateralization was quantified after CCAO and hindlimb femoral
      artery ligation comparing wild-type and DEP-1(-/-) mice. Both cerebral
      collateralization assessed by latex perfusion and peripheral vessel growth in the
      femoral artery determined by microsphere perfusion and micro-CT analysis were not
      altered in DEP-1(-/-) compared to wild-type mice. Cerebrovascular reserve
      capacity, however, was significantly impaired in DEP-1(-/-) mice. Cerebrovascular
      transcriptional analysis of proarteriogenic growth factors and receptors showed
      specifically reduced transcripts of PDGF-B. SiRNA knockdown of DEP-1 in
      endothelial cells in vitro also resulted in significant PDGF-B downregulation,
      providing further evidence for DEP-1 in PDGF-B gene regulation. In summary, our
      data support the notion of DEP-1 as positive functional regulator in vascular
      cerebral arteriogenesis, involving differential PDGF-B gene expression. 

PMID- 24027764
TI  - Patient complaint cases in primary health care: what are the characteristics of
      general practitioners involved?
AB  - BACKGROUND: Limited knowledge exists about factors increasing the risk of general
      practitioners becoming involved in a complaint case or getting disciplined in
      connection with a complaint case. AIM: The present study aimed to identify the
      general practitioner and practice characteristics associated with complaint cases
      and discipline. METHODS: Information on general practitioners involved in
      complaint case decisions during one year (2007) was linked to Danish National
      register data on all general practitioners (n = 3,765). Logistic regression was
      used for statistical analysis. RESULTS: With regard to complaints concerning
      daytime services (n = 265), the professional seniority of the general
      practitioner was positively associated with the odds of receiving a complaint
      decision (OR = 1.44 per 20 years of seniority; CI 95%, 1.04-1.98). Likewise,
      having more consultations per day was associated with increased odds (OR = 1.29
      per 10 extra consultations per day; CI 95%, 1.07-1.54). No statistically
      significant association could be demonstrated between being disciplined and
      general practitioner or practice characteristics. CONCLUSION: The possible
      relationship between professional seniority, rate of consultations, and complaint
      cases merits further studies to clarify the impact of professional seniority and
      workload on professional performance and to furthermore consider the role of
      factors such as job content and communication styles.

PMID- 24027765
TI  - Inflammatory bowel disease therapies and gut function in a colitis mouse model.
AB  - BACKGROUND: Exclusive enteral nutrition (EEN) is a well-established approach to
      the management of Crohn's disease. Aim. To determine effects of EEN upon
      inflammation and gut barrier function in a colitis mouse model. METHODS:
      Interleukin-10-deficient mice (IL-10(-/-)) were inoculated with Helicobacter
      trogontum and then treated with EEN, metronidazole, hydrocortisone, or EEN and
      metronidazole combination. Blood and tissue were collected at 2 and 4 weeks with
      histology, mucosal integrity, tight junction integrity, inflammation, and H.
      trogontum load evaluated. RESULTS: H. trogontum induced colitis in IL-10(-/-)
      mice with histological changes in the cecum and colon. Elevated mucosal IL-8 mRNA
      in infected mice was associated with intestinal barrier dysfunction indicated by
      decreased transepithelial electrical resistance and mRNA of tight junction
      proteins and increased short-circuit current, myosin light chain kinase mRNA,
      paracellular permeability, and tumor necrosis factor- alpha and myeloperoxidase
      plasma levels (P < 0.01 for all comparisons). EEN and metronidazole, but not
      hydrocortisone, treatments restored barrier function, maintained gut barrier
      integrity, and reversed inflammatory changes along with reduction of H. trogontum
      load (versus infected controls P < 0.05). CONCLUSION: H. trogontum infection in
      IL-10(-/-) mice induced typhlocolitis with intestinal barrier dysfunction. EEN
      and metronidazole, but not hydrocortisone, modulate barrier dysfunction and
      reversal of inflammatory changes.

PMID- 24027767
TI  - Poly beta-hydroxybutyrate production by Bacillus subtilis NG220 using sugar
      industry waste water.
AB  - The production of poly beta-hydroxybutyrate (PHB) by Bacillus subtilis NG220 was
      observed utilizing the sugar industry waste water supplemented with various
      carbon and nitrogen sources. At a growth rate of 0.14 g h(-1) L(-1), using sugar
      industry waste water was supplemented with maltose (1% w/v) and ammonium sulphate
      (1% w/v); the isolate produced 5.297 g/L of poly beta-hydroxybutyrate
      accumulating 51.8% (w/w) of biomass. The chemical nature of the polymer was
      confirmed with nuclear magnetic resonance, Fourier transform infrared, and GC-MS
      spectroscopy whereas thermal properties were monitored with differential scanning
      calorimetry. In biodegradability study, when PHB film of the polymer (made by
      traditional solvent casting technique) was subjected to degradation in various
      natural habitats like soil, compost, and industrial sludge, it was completely
      degraded after 30 days in the compost having 25% (w/w) moisture. So, the present
      study gives insight into dual benefits of conversion of a waste material into
      value added product, PHB, and waste management.

PMID- 24027766
TI  - Mechanisms of nanoparticle-induced oxidative stress and toxicity.
AB  - The rapidly emerging field of nanotechnology has offered innovative discoveries
      in the medical, industrial, and consumer sectors. The unique physicochemical and
      electrical properties of engineered nanoparticles (NP) make them highly desirable
      in a variety of applications. However, these novel properties of NP are fraught
      with concerns for environmental and occupational exposure. Changes in structural
      and physicochemical properties of NP can lead to changes in biological activities
      including ROS generation, one of the most frequently reported NP-associated
      toxicities. Oxidative stress induced by engineered NP is due to acellular factors
      such as particle surface, size, composition, and presence of metals, while
      cellular responses such as mitochondrial respiration, NP-cell interaction, and
      immune cell activation are responsible for ROS-mediated damage. NP-induced
      oxidative stress responses are torch bearers for further pathophysiological
      effects including genotoxicity, inflammation, and fibrosis as demonstrated by
      activation of associated cell signaling pathways. Since oxidative stress is a key
      determinant of NP-induced injury, it is necessary to characterize the ROS
      response resulting from NP. Through physicochemical characterization and
      understanding of the multiple signaling cascades activated by NP-induced ROS, a
      systemic toxicity screen with oxidative stress as a predictive model for NP
      induced injury can be developed. 

PMID- 24027769
TI  - Effect of Perilla frutescens fixed oil on experimental esophagitis in albino
      Wistar rats.
AB  - The present study was undertaken to elucidate the effect of Perilla frutescens
      fixed oil on experimental esophagitis in albino rats. A group of rats (n = 6),
      treated with control vehicle (0.9% NaCl in double distilled water, 3 mL/kg, i.p.)
      and Perilla frutescens fixed oil (100%) (1, 2, and 3 mL/kg, i.p.), or
      pantoprazole (30 mg/kg, i.p.), were subjected to 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. Treatment with fixed oil significantly inhibited the gastric secretion,
      total acidity, and esophagitis index. The oil also helped to restore the altered
      levels of oxidative stress parameters to normal. The present study also makes
      evident the in vitro antihistaminic and anticholinergic activity of alpha
      linolenic acid (ALA) (18 : 3, n - 3) on isolated rat ileum preparation. The
      lipoxygenase inhibitory, histamine antagonistic, antisecretory (anticholinergic),
      and antioxidant activity of the oil was attributed for its efficacy in reflux
      esophagitis.

PMID- 24027770
TI  - Microtensile bond strength to enamel affected by hypoplastic amelogenesis
      imperfecta.
AB  - PURPOSE: This study compared the microtensile bond strengths (MUTBS) of two
      different self-etching (SE) and etchand- rinse (ER) adhesive systems to enamel
      affected by hypoplastic amelogenesis imperfecta (HPAI) and analyzed the enamel
      etching patterns created by the two adhesive systems using scanning electron
      microscopy (SEM). MATERIALS AND METHODS: Sixteen extracted HPAI-affected molars
      were used for the bond strength tests and 2 molars were examined under SEM for
      etching patterns. The control groups consisted of 12 healthy third molars for
      MUTBS tests and two molars for SEM. Mesial and distal surfaces of the teeth were
      slightly ground flat. The adhesive systems and composite resin were applied to
      the flat enamel surfaces according to the manufacturers' instructions. The tooth
      slabs containing composite resin material on their mesial and distal surfaces
      were cut in the mesio-distal direction with a slow-speed diamond saw. The slabs
      were cut again to obtain square, 1-mm-thick sticks. Finally, each stick was
      divided into halves and placed in the MUTBS tester. Bond strength tests were
      performed at a speed of 0.5 mm/min. Data were analyzed with two-way ANOVA and
      Tukey's tests. RESULTS: There was no significant difference between the bond
      strength values of ER and SE adhesives (p > 0.05). However, significant
      differences were found between HPAI and control groups (p < 0.05). HPAI-affected
      enamel surfaces exhibited mild intra- and inter-prismatic enamel etching patterns
      after orthophosphoric acid application, while conditioning of HPAI-affected
      enamel with SE primer created a slightly rough and grooved surface. CONCLUSION:
      SE and ER adhesive systems provide similar bond strengths to HPAI-affected enamel
      surfaces.

PMID- 24027768
TI  - Radiation-induced noncancer risks in interventional cardiology: optimisation of
      procedures and staff and patient dose reduction.
AB  - Concerns about ionizing radiation during interventional cardiology have been
      increased in recent years as a result of rapid growth in interventional procedure
      volumes and the high radiation doses associated with some procedures. Noncancer
      radiation risks to cardiologists and medical staff in terms of radiation-induced
      cataracts and skin injuries for patients appear clear potential consequences of
      interventional cardiology procedures, while radiation-induced potential risk of
      developing cardiovascular effects remains less clear. This paper provides an
      overview of the evidence-based reviews of concerns about noncancer risks of
      radiation exposure in interventional cardiology. Strategies commonly undertaken
      to reduce radiation doses to both medical staff and patients during
      interventional cardiology procedures are discussed; optimisation of
      interventional cardiology procedures is highlighted. 

PMID- 24027771
TI  - Pressable feldspathic inlays in premolars: effect of cementation strategy and
      mechanical cycling on the adhesive bond between dentin and restoration.
AB  - PURPOSE: To evaluate the effect of the cementation strategy and mechanical
      cycling (MC) on the microtensile bond strength (MTBS) of feldspathic inlays
      cemented to premolars. MATERIALS AND METHODS: Forty-eight human premolars were
      prepared and porcelain inlays were produced. Specimens were allocated into 3
      groups, based on the cementation strategy: 1) conventional adhesive cementation
      (RelyX ARC, 3M ESPE): application of etch-and-rinse single bottle adhesive to
      dentin / ceramic surface treated with hydrofluoric acid (HF) and silane (S) /
      cementation with resin cement; 2) simplified cementation using a self-adhesive
      resin cement (RelyX U100, 3M ESPE); 3) modified simplified cementation using a
      self-adhesive resin cement (RelyX U100, 3M ESPE) with HF+S treatment. Half of the
      specimens from each group were submitted to MC (2x106 pulses, frequency = 4 Hz,
      load = 100 N). Each specimen was serially sliced for MTBS and the failures were
      classified. The stress distribution analysis using FEA was verified. RESULTS: All
      of the bar-samples from G2 were lost during cutting of the specimens. Mechanical
      cycling had no significant effect on bond strength, whereas cementation strategy
      significant affected MTBS results. The most common type of failure was cohesive
      of cement. FEA showed that stresses were concentrated mainly at the loading
      region going up to the root fixation. CONCLUSION: Porcelain inlays cemented with
      conventional resin cement or self-adhesive resin cement should be associated with
      ceramic surface treatment. FEA showed the most critical zone for failure is
      located in the cement region close to the marginal crest.

PMID- 24027772
TI  - Effect of chlorhexidine and ethanol on push-out bond strength of fiber posts
      under cyclic loading.
AB  - PURPOSE: To investigate the effects of pretreatment with 2% chlorhexidine in a
      gel base (CHX) and 100% ethanol (EtOH) on the bond strength between fiber posts
      relined with resin composite and root dentin under cyclic loading. MATERIALS AND
      METHODS: Forty bovine incisor roots were divided into four groups after
      phosphoric acid etching: group 1 (control), irrigation with physiological saline
      solution; group 2, 5 min pretreatment with CHX; group 3, 1 min pretreatment with
      EtOH; group 4, 5 min pretreatment with CHX followed by 1 min with EtOH. Fiber
      posts relined with resin composite were cemented with RelyX ARC and the etch-and
      rinse adhesive system Scotchbond Multi-Purpose. Each group was randomly divided
      into two subgroups: 24 h of storage (immediate groups) and cyclic loading
      (loading groups) with 250,000 cycles in a controlled chewing simulator. All roots
      were sectioned transversely and push-out tests were performed. Failure modes were
      observed and the bond strength means were analyzed using ANOVA and Tukey's test
      (a = 0.05). RESULTS: The mean values for the bond strength test (MPa) in
      immediate groups were: group 1, 5.44 +/- 1.48; group 2, 5.57 +/- 1.41; group 3,
      5.49 +/- 1.48; group 4, 5.57 +/- 1.42. Immediate groups showed similar bond
      strength values (p > 0.05). In the cyclic loading groups, the bond strength
      values were: group 1, 2.80 +/- 0.79; group 2, 4.02 (1.30); group 3, 4.50 +/-
      1.67; group 4, 4.97 +/- 2.00. After cyclic loading, a significant decrease in the
      control group was observed (p < 0.05), while CHX pretreatment resulted in
      intermediate values (p < 0.05) and EtOH alone or associated with CHX preserved
      the bond strength values (p > 0.05). CONCLUSION: Chlorhexidine and/or ethanol
      pretreatment preserved the bond strength of the fiber post after cyclic loading.

PMID- 24027776
TI  - Quantitative analysis of aberrant protein glycosylation in liver cancer plasma by
      AAL-enrichment and MRM mass spectrometry.
AB  - A lectin-coupled mass spectrometry (MS) approach was employed to quantitatively
      monitor aberrant protein glycosylation in liver cancer plasma. To do this, we
      compared the difference in the total protein abundance of a target glycoprotein
      between hepatocellular carcinoma (HCC) plasmas and hepatitis B virus (HBV)
      plasmas, as well as the difference in lectin-specific protein glycoform abundance
      of the target glycoprotein. Capturing the lectin-specific protein glycoforms from
      a plasma sample was accomplished by using a fucose-specific aleuria aurantia
      lectin (AAL) immobilized onto magnetic beads via a biotin-streptavidin conjugate.
      Following tryptic digestion of both the total plasma and its AAL-captured
      fraction of each HCC and HBV sample, targeted proteomic mass spectrometry was
      conducted quantitatively by a multiple reaction monitoring (MRM) technique. From
      the MRM-based analysis of the total plasmas and AAL-captured fractions,
      differences between HCC and HBV plasma groups in fucosylated glycoform levels of
      target glycoproteins were confirmed to arise from both the change in the total
      protein abundance of the target proteins and the change incurred by aberrant
      fucosylation on target glycoproteins in HCC plasma, even when no significant
      change occurs in the total protein abundance level. Combining the MRM-based
      analysis method with the lectin-capturing technique proved to be a successful
      means of quantitatively investigating aberrant protein glycosylation in cancer
      plasma samples. Additionally, it was elucidated that the differences between HCC
      and control groups in fucosylated biomarker candidates A1AT and FETUA mainly
      originated from an increase in fucosylation levels on these target glycoproteins,
      rather than an increase in the total protein abundance of the target
      glycoproteins. 

PMID- 24027777
TI  - Analysis of single algal cells by combining mass spectrometry with Raman and
      fluorescence mapping.
AB  - In order to investigate metabolic properties of single cells of freshwater algae
      (Haematococcus pluvialis), we implement matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) in combination with
      microspectroscopic mapping. Straightforward coupling of these two detection
      platforms was possible thanks to the self-aliquoting properties of micro-arrays
      for mass spectrometry (MAMS). Following Raman and fluorescence imaging, the
      isolated cells were covered with a MALDI matrix for targeted metabolic analysis
      by MALDI-MS. The three consecutive measurements carried out on the same cells
      yielded complementary information. Using this method, we were able to study the
      encystment of H. pluvialis - by monitoring the adenosine triphosphate (ATP) to
      adenosine diphosphate (ADP) ratio during the build-up of astaxanthin in the cells
      as well as the release of beta-carotene, the precursor of astaxanthin, into the
      cytosol. 

PMID- 24027778
TI  - Human cytochrome P450 3A4 and a carbon nanofiber modified film electrode as a
      platform for the simple evaluation of drug metabolism and inhibition reactions.
AB  - Electrochemical biosensors consisting of cytochrome P450 enzyme modified
      electrodes have been developed to provide a simple method for screening the
      metabolism of a drug and its inhibitor. Here, we report a very simple
      electrochemically driven biosensor for detecting drug metabolism and its
      inhibition based on cytochrome P450 3A4 (CYP3A4) and a carbon nanofiber (CNF)
      modified film electrode without any other modified layers such as mediator films.
      Direct electron transfer (DET) between CYP3A4 and CNFs was observed at a formal
      potential of -0.302 V. The electrocatalytic reduction current increased with the
      addition of drugs including testosterone and quinidine. In contrast, the
      reduction current was greatly suppressed in the presence of ketoconazole, which
      is a CYP3A4 inhibitor. CNFs with high conductivity, a large surface area and
      sufficient edge planes provide a suitable microenvironment for achieving
      excellent DET and biocatalysis properties, which could not be observed when we
      used other carbon materials such as carbon nanotube (CNT) and carbon black (CB)
      modified electrodes, indicating that our system is promising as a new
      bioelectronic platform for electrochemical biosensing. 

PMID- 24027779
TI  - Mechanochemical and silica gel-mediated formation of highly electron-poor 1
      cyanocarbonylferrocene.
AB  - Simple manual grinding of solid cyanomethylferrrocene (1) and silica gel provides
      a facile one-pot access route to prepare unexpected and highly electron-poor
      metallocene, 1-cyanocarbonylferrocene (2). Electrochemical measurements supported
      by computational studies reveal that 2 exhibits the highest Fe(II)/Fe(III)
      oxidation potential reported for mono-substituted ferrocenes.

PMID- 24027780
TI  - Response to letter regarding article, "percutaneous left-ventricular support with
      the impella-2.5-assist device in acute cardiogenic shock results of the Impella
      EUROSHOCK registry".

PMID- 24027781
TI  - Response to Letter Regarding Article, "Galectin-3 and Cardiac Function in
      Survivors of Acute Myocardial Infarction".

PMID- 24027783
TI  - Complications following dislocations of the proximal interphalangeal joint.

PMID- 24027782
TI  - Probe of the solar magnetic field using the "cosmic-ray shadow" of the sun.
AB  - We report on a clear solar-cycle variation of the Sun's shadow in the 10 TeV
      cosmic-ray flux observed by the Tibet air shower array during a full solar cycle
      from 1996 to 2009. In order to clarify the physical implications of the observed
      solar cycle variation, we develop numerical simulations of the Sun's shadow,
      using the potential field source surface model and the current sheet source
      surface (CSSS) model for the coronal magnetic field. We find that the intensity
      deficit in the simulated Sun's shadow is very sensitive to the coronal magnetic
      field structure, and the observed variation of the Sun's shadow is better
      reproduced by the CSSS model. This is the first successful attempt to evaluate
      the coronal magnetic field models by using the Sun's shadow observed in the TeV
      cosmic-ray flux.

PMID- 24027784
TI  - Animals represent the past and the future.
AB  - It has been proposed by some that only humans have the ability to mentally travel
      back in time (i.e., have episodic memory) and forward in time (i.e., have the
      ability to simulate the future). However, there is evidence from a variety of
      nonhuman animals (e.g., primates, dolphins, scrub jays, rats, and pigeons) that
      they have some ability to recover personal memories of what-where-when an event
      occurred (an earlier requirement of the ability to recover an episodic memory)
      and answer unexpected questions (another requirement to distinguish between
      semantic and episodic memory). Also, perhaps more critically, according to
      Tulving's more recent definition of mental time-travel, several animals (primates
      and scrub jays) have been shown to be able to pass the spoon test. That is, they
      are able to plan for the future. Thus, although humans show an advanced ability
      to mentally travel backward and forward in time, there is growing evidence that
      nonhuman animals have some of this capacity as well.

PMID- 24027785
TI  - Response to hypoadiponectinemia and endogenous nitric oxide synthase inhibitor in
      hypertension.

PMID- 24027786
TI  - Research review: the role of cytokines in depression in adolescents: a systematic
      review.
AB  - BACKGROUND: While cytokines have been implicated in the pathophysiology of
      depression in adults, the potential role in younger age groups such as
      adolescents is less clear. This article therefore reviews the literature (a) to
      explore the relationship between cytokines and depression in adolescents, and (b)
      to examine how cytokines may be related to adolescent depression in the context
      of other neurobiological theories of depression. METHOD: A systematic review of
      the scientific literature on the subject was conducted in February 2013,
      searching the Web of Knowledge, PubMed (Medline), PsycInfo and Cochrane
      electronic databases. RESULTS: Eighteen studies were identified measuring both
      depression or depressive symptoms and cytokines or immune markers in adolescents.
      Adolescents with depression show age-specific characteristics of the immune and
      inflammatory system, specifically in NK cell activity and in pro-inflammatory
      cytokines (such as IL-1beta and TNF-alpha). In addition, the role of cytokines in
      adolescent depression is influenced by neurodevelopment, hormonal changes, stress
      and trauma. CONCLUSIONS: There may be differences in the neurobiology of
      adolescent major depressive disorder (MDD) compared with adult MDD. Increased
      understanding of the role of cytokines in adolescent MDD may lead to improved
      outcomes in the treatment of adolescent depression.

PMID- 24027787
TI  - Reply to H Hemila.

PMID- 24027788
TI  - Reply to LE Armstrong et al.

PMID- 24027789
TI  - Reply to E Falk Libby et al.

PMID- 24027790
TI  - Eponyms in cardiopulmonary reflexes.
AB  - Heart rate, blood pressure, and vascular tone, as well as ventilator drive,
      respiratory rate, and breathing pattern, are, at least in part, under the control
      of specific reflexes. These reflexes are mediated by a complex network of
      baroreceptors and chemoreceptors in the arterial system of the carotids, aorta,
      and left heart, including receptors in the left atrium, the ventricle, and the
      coronary arteries; irritants in the upper airways and stretch receptors in the
      lower airways; juxtacapillary-located nonmyelinated fibers in the alveoli and in
      the bronchial arterial system; and muscle spindles that evoke changes in the
      membrane potential upon alteration of sarcolemmal tension. Some of these
      reflexes, usually named after the first individual to describe them, have spread
      as eponyms into propaedeutic education and clinical work. Because these euphonic
      eponyms are enigmatic to most clinicians today, this article is intended to
      provide a short overview of these reflexes, including the historical context of
      their describers. As evidenced by their clinical implications, the eponyms
      discussed are revealed to be more than curiosities taught during undergraduate
      medical education.

PMID- 24027791
TI  - Reply to FS Dioguardi.

PMID- 24027792
TI  - Reply to MP Pase and C Stough.

PMID- 24027807
TI  - [Nursing diagnostic classification NANDA-I: the latest version is available].

PMID- 24027808
TI  - [Sequence phylogenetic analysis based on VPI gene of coxsackievirus A16 strains
      isolated in Inner Mongolia, China].

PMID- 24027809
TI  - [Cloning, expression and activity determination of capsid protein VP1 of
      enterovirus type 71].

PMID- 24027810
TI  - [Q & A. The disease suggested by diagnostic imaging].

PMID- 24027811
TI  - Back to basics: a day in the life of a hospital case manager--Part 2.

PMID- 24027812
TI  - The promise of mobile: connecting to underserved populations.

PMID- 24027813
TI  - CIOs beef up their RCM operations in the post-reform world.

PMID- 24027814
TI  - The many roadblocks of creating an ACO.

PMID- 24027815
TI  - Usability in an EMR: a long journey. Interview by Gabriel Perna.

PMID- 24027816
TI  - Donald Berwick urges: transform healthcare.

PMID- 24027817
TI  - Payer partnerships and population health.

PMID- 24027818
TI  - Weighing two job offers.

PMID- 24027819
TI  - [The San Francisco Declaration--impact factor must not be used to assess an
      scientists contributions].

PMID- 24027820
TI  - [The structural and functional diversity of bioactive peptide].

PMID- 24027821
TI  - [Salusins and its cardiovascular effects].
AB  - Salusins are newly discovered cardiovascular active peptides, including salusin
      alpha and salusin-beta, which are peptides containing 28 and 20 amino acids
      respectively. Salusins are widely distributed in tissuse and organs of human and
      rat, and have a series of cardiovascular effects, including lowering blood
      pressure, slowing down the heart rate, inhibiting myocardial contraction,
      reducing cardiac ischemic injury, and promoting hypertrophy of cardiomyocytes and
      proliferation of vascular smooth muscle cells. It is noteworthy to mention that
      salusin-alpha and salusin-beta are polypeptides produced by the same precursor
      and play opposite roles in the development and progression of atherosclerosis.

PMID- 24027822
TI  - [The diversity of ghrelin gene in its products and functions].
AB  - By alternative splicing and posttranslational modification, ghrelin gene encodes
      multiple products ranging from acyl-ghrelin, des-acyl-ghrelin, to obestatin.
      These products exhibit diverse functions such as stimulating growth hormone
      secretion, regulating food uptake, glucose and lipid metabolism, protecting
      cardiovascular system, and modulating immune and inflammation. This review
      summarizes the recent advances on the products of ghrelin gene and their diverse
      functions.

PMID- 24027823
TI  - [Cardiovascular effects and pathophysiological significance of adrenomedullin
      family peptides].
AB  - Adrenomedullin family includes adrenomedullin (ADM), intermedin (IMD) and
      different peptide fragments derived from prepro-ADM or prepro-IMD. Recent
      researches found the interaction between different prepro-peptides or different
      peptide fragments, which plays a crucial role in maintaining homeostasis of
      cardiovascular system as well as participates in the occurrence and development
      of cardiovascular disease. This review intends to introduce cardiovascular
      effects and pathophysiological significance of adrenomedullin family peptides
      from function level, receptor level and signaling pathway.

PMID- 24027824
TI  - [Network regulation of renin-angiotensin system on the cardiovascular diseases].
AB  - It is well established that renin-angiotensin system (RAS) is the major
      regulatory network that maintains blood pressure, fluid and electrolyte balance,
      and involves the pathogenesis and development of cardiovascular system. Recently,
      studies on RAS has made remarkable achievements, angiotensin-converting enzyme
      inhibitors and angiotensin receptor inhibitors has become the first-line drug for
      clinical treatment of hypertension and other cardiovascular diseases. Recent
      identification of multiple products degraded from angiotensin I, enzymes and
      receptors have proved that RAS has become a complex network regulating system. In
      order to better understand the mechanism of RAS regulation, this article intends
      to introduce the main members of RAS and its network regulation effects in
      cardiovascular system from enzyme level, metabolite level, receptor level, and
      signaling pathway.

PMID- 24027825
TI  - [Distribution and regulation of Panx1 protein].
AB  - Pannexin1 (Panx1) is a subtype of the newly discovered gap junction proteins
      named Pannexin(s). Panx1 is widely expressed in the nervous system,
      cardiovascular system, etc and can form non-selective and large conductance
      hemichannel. It has been demonstrated that various conditions can regulate Panx1
      open and affect the body's physiological function via macromolecular substance
      (for instance, ATP) releasing. This review gives a detailed introduction to the
      main distribution of Panxl, summarizes the open and inhibition condition of
      Panx1, and finally, prospects directions of future research.

PMID- 24027826
TI  - [Physiological and pathophysiological function of myocardial autophagy].
AB  - Autophagy is a fundamental catabolism process widely existing in organisms,
      through which intracellular components such as long-lived proteins and organelles
      can be degraded. A certain degree of autophagy is a kind of endogenous protective
      mechanism, participating in adaptive immune response. Insufficient or excessive
      autophagy will disturb cell homeostasis, aggravate or cause cell death. Numerous
      studies demonstrate a marked increase in cardiac autophagic activity under a wide
      range of disease states and in response to diverse stimuli. Recently, despite of
      its dual nature, autophagy has been widely promoted as a potential therapeutic
      target for the treatment of cardiovascular disease and heart failure. In the
      current report, we review research progresses on the physiological and
      pathophysiological function and the molecular mechanism of cardiac autophgy, so
      as to find new methods for the heart diseases treatment.

PMID- 24027827
TI  - [Death/survival signaling pathways in cerebral ischemia and the developing
      therapeutic strategies].
AB  - In an aging society, the incidence of brain ischemia increases dramatically.
      Despite progress in pathophysiology mechanisms, the medical therapy for brain
      ischemia has not been satisfactory. Recanalization using tissue plasminogen
      activator only modestly improves patient outcome, and inhibiting excitotoxicity
      has shown no clinical benefit. Both do not provide an adequate time window for
      effective stroke therapy in clinical practice. A more reasonable therapeutic
      window, and hence a greater potential for clinical success, is likely to be
      attained by placing emphasis on ameliorating the effects of the synergistic
      processes of programmed cell death (PCD) that is active for hours to days after
      ischemia. It is necessary to identify molecular mediators of ischemic
      neuroprotection suitable for translation to human clinical trials. In this
      review, the mechanisms of cell death/survival signaling pathways after ischemia
      and the potential therapeutic targets will be discussed.

PMID- 24027828
TI  - [Advance and future of research on gut homeostasis and related diseases].

PMID- 24027829
TI  - [Regulation of p16(INK4) mRNA turnover in cellular senescence].

PMID- 24027830
TI  - [The role of epithelial to mesenchymal transition in chronic respiratory
      diseases].

PMID- 24027831
TI  - [The role of nesfatin-1 in obesity and glucose regulation].

PMID- 24027832
TI  - [Roles of vitamin D in cardiovascular diseases].

PMID- 24027833
TI  - [Developmental changes of excitation-contraction coupling in the postnatal
      mammalian heart].

PMID- 24027834
TI  - [Mitochondrial uncoupling protein UCP2 and cancer].

PMID- 24027835
TI  - [Autophagy-emerging mechanism in exercise ameliorating insulin resistance].

PMID- 24027836
TI  - [The development of dispensarization of population in presents conditions].
AB  - The article considers the development of dispensarization of population,
      including new tasks, possible obstacles in the content of this work and
      approaches to overcome them.

PMID- 24027837
TI  - [The health policy as a problem of comprehension].
AB  - The article deals with the issues of health policy elaboration in the framework
      of scientific philosophic concept of comprehension. The validity of application
      of criterion of mode and criterion of compliance in assessment of health policy
      effectiveness is justified The key role of managerial blocks of commitments
      assumption and responsibilities performance in health policy strategic management
      is demonstrated. The importance of incorporation of component of moral
      appropriateness of health activities into health policy design is emphasized.

PMID- 24027838
TI  - [The scope and structure of ambulatory polyclinic visits of physicians in the
      Russian Federation in 2009-2011].
AB  - The article presents the results of structural functional analysis of public
      statistic data concerning the appealability of population the Russian Federation
      for ambulatory polyclinic care in health institutions of Minzdrav of Russia in
      2009-2011. The study was targeted to identify the institutions, the volume, the
      specialists, the groups of population and purpose of provided medical care. It is
      demonstrated that during three years the significant differences in volume and
      structure of ambulatory polyclinic care used per capita between adults and
      children, urban and rural residents still are present. This is an indication of
      different degree of need and availability of this kind of medical care. It is
      noted that in ambulatory polyclinic institutions the specialized medical care is
      provided mainly on the occasion of diseases. This situation is not fully in line
      with present conceptions of targets of this stage of medical care provision.

PMID- 24027839
TI  - [The quantitative estimates of identification of diseases in medical institutions
      of different form of property and departmental belonging].
AB  - The results of analysis of actual situation in the field of medical care
      provision to population by medical institutions of different form of property and
      departmental belonging demonstrated that the percentage of additionally
      identified cases of pathology of blood circulation system comes up to 20% and
      more in certain territories. This occurrence mainly depends on organization of
      medical care of population in the field and development of medical institutions
      network outside the system of Minzdrav of Russia. It is needed to further
      elaborate the process of getting the data specifying the statistics of pathology
      propagation.

PMID- 24027840
TI  - [The characteristics of chronic patients referred in oblast counseling polyclinic
      for medical consultation].
AB  - The article presents the results of expertise of 506 appointment cards of chronic
      patients consultation to physicians-specialists in oblast polyclinic. The
      analysis established the social demographic characteristics of patients, advanced
      cases, percentage of ungrounded and untimely appointments, scope of care provided
      in the oblast curative preventive establishment and need of patients in
      continuation of treatment at place of residence. The conclusions and
      recommendations make it possible to optimize the selection of patients referred
      to oblast polyclinic and to enhance the quality of medical care of rural
      population.

PMID- 24027841
TI  - [The health conditions of adolescents as a conscription resource].
AB  - The article analyzes the dynamics of main health indicators of youth adolescents
      aged 15-18 years from the point of view of readiness to serve in the armed forces
      of the Russian Federation. The actual aspects of organization of medical
      examination of conscripts are considered. The ten years dynamics of indicators of
      morbidity of adolescents aged 15-17 years of Moscow oblast was studied in
      comparison with the data from the Central federal okrug and Russia in general.
      The activity of medical organizations and medical personnel is studied The main
      resources of enhancement and implementation in the territories of measures within
      the framework of the governmental Concept of federal program of training of
      citizen for military service up to 2020 are identified. The practice
      recommendations are developed concerning the optimization medical support of
      youth training for military service, intersectorial integration, enhancement of
      the role of pediatric service first of all the children polyclinics in the field
      of effective implementation of tasks of recruitment of army with healthy
      contingent.

PMID- 24027842
TI  - [The infection security as a criterion of evaluation of medical services
      quality].
AB  - The article presents the results od sociological survey concerning the evaluation
      of quality and security of both provided medical care and the organization of the
      system of infection security in ambulatory polyclinic institutions. The
      evaluation of conformity of disinfection devices to modern level is presented.
      The de3gree of training of respondents concerning the issues of disinfection and
      sterilization during medical care provision are discussed.

PMID- 24027843
TI  - [The order of neurosurgical care provision].
AB  - The article considers the issues concerning the order of medical care provision
      in neurosurgery taking on account the particularities of the Chechen republic.
      The characteristics of clinical course of diseases and traumas on neural system
      are considered too to improve the organization of neurosurgical care in concrete
      territory.

PMID- 24027844
TI  - [About formation of actual comprehension of palliative care].
AB  - The article emphasizes that the palliative medical care is considered in the
      Federal law "On the fundamentals of health care of citizen in the Russian
      Federation" (2011)as one of the types of medical care of population. The Orders
      of delivery of palliative care to adult population and children are in the
      process of development to determine in perspective the formation of palliative
      care services in the regions. The successful development of this service needs a
      clear-cut definition of palliative care to formulate the corresponding tasks and
      contingents of patients. The Preference is to be given to the definition which
      considers palliative medical care as a medical care of patients with diagnosis of
      active incurable progressing disease at the stage when possibilities of
      specialized/radical treatment are exhausted or limited.

PMID- 24027845
TI  - [The military medical expertise of conscripts and its quality].
AB  - The article considers the issues of defects in functioning of conscripting
      military medical commissions using the analysis of long standing statistical data
      concerning the changes of category of physical fitness of young conscripts
      arrived to reinforce the Northern fleet. The study used the materials of reports
      of the results of medical examination of young reinforcement in 2002-2011. The
      analysis of 847 disease certificates of conscripts referred to hospital check-up
      with following health examination by military medical commission of the fleet to
      reveal diseases blocking the military service admission. The probability model is
      presented of comorbidity among conscripts to enhance the validity of planning of
      curative health promoting activities in youth generation. It is proposed during
      planned control of military commissariats to consider as a separate control
      elements the analysis of implementation of planned curative health promoting
      activities concerning conscripts on individual and group levels. The same
      position is proposed to apply to number of conscripted citizen who were send to
      military forces but at a later date were admitted as limitedly fitted for
      military service and not fitted for military service at conscription.

PMID- 24027846
TI  - [The development of activity of supporting curative diagnostic service].
AB  - The article presents the role and significance of retrospective analysis of
      volumes of consumption of various types of diagnostic services to develop the
      activity of supportive curative diagnostic service.

PMID- 24027847
TI  - [The characteristics of medical manpower of dermatologic venereal service at the
      territorial level].
AB  - The article presents the medical social characteristics of medical manpower af
      dermatologic venereal services of Ryazan, Tula and Lipetsk oblasts from the
      position of quality of specialized medical care of population.

PMID- 24027848
TI  - [The public health legislation in conditions of globalization].
AB  - The article demonstrates the impact of globalization on development of public
      health legislation at the international level and in particular countries. The
      legislation is considered as a tool to decrease the globalization health risks
      for population

PMID- 24027849
TI  - [The reference pricing of pharmaceuticals in European countries].
AB  - The article presents the analysis of various approaches to estimation of
      pharmaceuticals prices in conditions of actual systems of pharmaceuticals
      support. The pricing is considered in pegging to actual systems of
      pharmaceuticals support based on the principles of insurance and co-financing.
      The detailed analysis is presented concerning the methodology of estimation of
      reference prices of pharmaceuticals in different countries of Europe. The
      experience of European countries in evaluation of interchangeability of
      pharmaceuticals is discussed.

PMID- 24027850
TI  - [The marketing analysis of assortment of market of pharmaceuticals applied in
      treatment of psoriasis in Ukraine].
AB  - The analysis of assortment of pharmaceuticals for treatment of psoriasis
      recommended by Minzdrav of Ukraine and present at the national pharmaceutical
      market is made. The characteristics of distribution of national and foreign
      producers of antihistamine and anti-psoriatic pharmaceuticals are established The
      availability of particular medicinal forms of various producers is analyzed too.
      The characteristics and tendencies in consumption of these groups of
      pharmaceuticals in natural and monetary units are analyzed including dynamics of
      changes of mean wholesale prices during the analyzed period.

PMID- 24027851
TI  - [The becoming of public medicine in the second half of XVIII-first half of XIX
      centuries. Report III. The sanitary routine in Western Europe].
AB  - The present report is dedicated to consideration of conditions of life, diet and
      labor activity of population of Western Europe n the second half of XVIII-first
      half of XIX centuries. The literary monuments, published testimonials of
      witnesses, materials from medical guidebooks and handbooks of those times are
      used to present the data concerning the anti-sanitary conditions of settlements,
      residential and public buildings and lacking of personal cleanliness among
      population. The issues are considered relating to inadequate quantity and low
      quality of food The exploitation of female and children labor in factory
      manufacture and dramatic moral degradation of fabric workers is considered too.
      The overall impact of these factors on mass morbidity and mortality of population
      is analyzed.

PMID- 24027852
TI  - [The medical support of resettlement of peasants in Siberia during the Stolypin
      reform].
AB  - The article considers the organization of medical care of settlers en route and
      in places of their settlement beyond the Ural during the Stolypin agrarian
      reform. The role of P.A. Stolypin, the Chairman of Council of ministers is
      demonstrated concerning the application of urgent measures on improvement of
      functioning of departments, controlling the resettlement and arrangement of
      peasants at new places. The development of resettlement medicine patterned after
      zemstvo medicine enhanced the penetration of scientific medicine into
      inaccessible regions of country.

PMID- 24027853
TI  - [E.A. Yunge and his role in education of ophthalmology in the Moscow University].
AB  - The article considers the issues of organization of process of education at the
      medical faculty of Moscow University in the second half of nineteen century.

PMID- 24027854
TI  - [Sinonasal inverted papilloma: a current review].

PMID- 24027855
TI  - Endoscopic sinus surgery for otolaryngological complications associated with
      dental and oral surgical treatment: a report of three illustrative cases.
AB  - Maxillary sinusitis is one of the most serious complications associated with
      dental implantation. When local dental treatment with or without antibiotics is
      not effective, Caldwell-Luc operation is often performed by an oral surgeon. We
      propose that endoscopic sinus surgery should be employed more widely as the first
      surgical treatment of choice for odontogenic maxillary sinusitis. This surgery
      aims to restore ventilation and drainage of paranasal sinuses by correcting the
      anatomical structures in the nasal cavity and paranasal sinuses intranasally.
      Unlike Caldwell-Luc procedure, the mucosa in the maxillary sinus is not totally
      removed; only highly polypous tissue is removed without exposing its bone
      surface. Resection of infected foci in the alveolar ridge or maxillary floor,
      when necessary, can be achieved intraorally both during or after endonasal sinus
      surgery. Postoperative care of irrigating the maxillary sinus with a saline
      solution at home is usually sufficient to eliminate the inflammation. Aeration of
      the maxillary sinus is restored without its deformation. Thus, endoscopic sinus
      surgery is much less invasive and more physiologic, as compared with the classic
      Caldwell-Luc operation. However, this surgery can be performed safely and
      securely only by an experienced and trained otolaryngologist. The authors
      strongly advocate a close collaboration between the dentist or oral surgeon and
      the otolaryngologist in treating maxillary sinusitis that develops in association
      with dental illness or treatment such as apical periodontitis, tooth extraction,
      and implantation. Three illustrative cases are reported.

PMID- 24027856
TI  - Topical bethanechol for the improvement of esophageal dysmotility: a pilot study.
AB  - OBJECTIVES: We studied a case series to evaluate the effect of topical
      bethanechol chloride on esophageal function in individuals with ineffective
      esophageal motility. METHODS: Five subjects with ineffective esophageal motility
      underwent high resolution esophageal manometry. Ten 5 mL liquid swallows were
      performed to establish a baseline. Five milligrams of topical bethanechol was
      then administered. After 10 minutes, the subjects completed 10 additional liquid
      swallows. This procedure was repeated with 10 mg of bethanechol in 4 subjects.
      RESULTS: After administration of 5 mg of topical bethanechol, the mean (+/- SD)
      distal contractile integral, an index of esophageal contractility, increased from
      178.3 +/- 83.1 mm Hg x s x cm to 272.3 +/- 216.9 mm Hg x s x cm (p = 0.69). The
      percentage of failed swallows decreased from 52.8% +/- 33.2% to 29.4% +/- 18.3%
      (p = 0.14). The percentage of peristaltic swallows increased from 28.0% +/- 26.8%
      to 67.2% +/- 15.3% (p = 0.04). The contractile front velocity was essentially
      unchanged. After administration of 10 mg of bethanechol,the distal contractile
      integral decreased from 349.3 +/- 371.0 mm Hg x s x cm to 261.8 +/- 293.5 mm Hg x
      s x cm (p = 0.72). The percentage of failed swallows increased from 57.5% +/-
      37.7% to 66.8% +/- 24.9% (p = 0.46). The percentage of peristaltic swallows
      increased from 17.5% +/- 23.6% to 28.3% +/- 19.1% (p = 0.29). The contractile
      front velocity decreased from 11.6 +/- 5.2 cm/s to 4.9 +/- 3.0 cm/s (p = 0.32).
      No adverse side effects occurred. CONCLUSIONS: The results of this pilot study
      support the need for further investigation with larger sample sizes and dose
      escalation.

PMID- 24027857
TI  - Otologic iontophoresis: a no-papoose technique.
AB  - OBJECTIVES: We describe a new iontophoresis solution, used in conjunction with a
      new iontophoresis system for achieving anesthesia of the tympanic membrane before
      myringotomy and insertion of pressure equalization tubes in an office setting.
      METHODS: We selected 50 patients (86 ears) who met standard indications for
      myringotomy only or myringotomy and pressure equalization tube insertion for a
      single-site consecutive series trial (Institutional Review Board-approved;
      informed consent and assent) in the authors' clinical practice. Topical
      anesthesia was obtained with a new US Food and Drug Administration-cleared
      iontophoresis system (Acclarent, Inc, Menlo Park, California) and a novel
      iontophoresis solution mixture. The Wong-Baker FACES Pain Rating Scale was used
      to assess the tolerability of the iontophoresis system with the new solution and
      of the otologic procedure after topical anesthesia was obtained. RESULTS:
      Iontophoresis success was obtained in 78 of 86 ears (90.7%). The average pain
      score for patients after iontophoresis was 1.07 on a 0-to-5 scale of increasing
      pain. The ear treatment was successful in 70 of 78 ears (89.7%). The average pain
      score for the surgical procedure was 1.19. CONCLUSIONS: This study demonstrates
      the safety and clinical effectiveness of the Acclarent iontophoresis system in
      conjunction with a new iontophoresis solution for anesthesia of the tympanic
      membrane in an office setting. This solution and device enable otologic
      procedures in children as young as 12 months of age without the use of a papoose,
      premedication, or general anesthesia.

PMID- 24027858
TI  - Globus pharyngeus: effectiveness of treatment with proton pump inhibitors and
      gabapentin.
AB  - OBJECTIVES: This study was performed to investigate the effectiveness of
      treatment of globus pharyngeus with proton pump inhibitors, gabapentin, or both.
      METHODS: The subjects all presented with globus pharyngeus during the years 2006
      to 2011. The inclusion criteria included a chief (primary) complaint of globus
      pharyngeus; a trial of proton pump inhibitor therapy for at least 2 months and/or
      a trial of gabapentin for at least 2 weeks; and at least 1 follow-up visit. We
      reviewed 331 charts; 87 patients met the criteria. The response to treatment was
      graded as none, partial, or complete. RESULTS: Seventy-seven percent of all
      patients had improvement. Sixty-seven percent of patients had a partial or
      complete response from aggressive reflux management. Sixty-six percent of
      patients who had a trial of gabapentin reported improvement. Eight of 14 patients
      who did not improve with aggressive reflux management improved with gabapentin.
      CONCLUSIONS: A majority of patients with globus pharyngeus can be helped by
      treating reflux or neuralgia. A trial of gabapentin should be considered for
      patients who do not respond or only partially respond to reflux management.

PMID- 24027859
TI  - Glottic bamboo nodules from systemic lupus erythematosus.
AB  - Bamboo nodules of the glottis are of late being described as a distinct entity
      seen in patients with autoimmune diseases. We report the symptoms, clinical
      features, and management of a case of bamboo nodules of the glottis in a patient
      with systemic lupus erythematosus. We discuss the pathogenesis and management of
      this condition on the basis of a review of the medical literature.

PMID- 24027860
TI  - Analysis of long-term hearing gains after stapes surgery with piston
      reconstruction for otosclerosis.
AB  - OBJECTIVES: We sought to assess the postoperative hearing gains at individual
      frequencies after stapes surgery with piston reconstruction for clinical
      otosclerosis. METHODS: We analyzed the air conduction (AC) hearing gains at
      various audiometric frequencies in a sample of 1,168 stapes procedures with
      piston reconstruction performed on 911 strictly consecutive patients by one
      surgeon between 1963 and 1979. Assiduous follow-up of patients was attempted for
      at least 10 years. The audiometric results over time were stored for computer
      analysis. RESULTS: The mean AC gain over the speech frequencies (0.5, 1,2, and 3
      kHz) was 35.5 dB at 1 year after operation, and the rate of deterioration over
      the next 19 years was 0.58 dB/y. CONCLUSIONS: The picture to emerge from the
      analysis is clear. The mean AC gain is maximal at nearly 40 dB for the
      audiometric frequencies of 0.25, 0.5, and 1 kHz. The mean AC gain at any given
      time after operation decreases with increasing frequency, at least for
      frequencies of > or = 1 kHz. For any frequency there is, with few exceptions, a
      significant decrease in the AC gain from one time period to the next.

PMID- 24027861
TI  - Voice symptoms and voice-related quality of life in college students.
AB  - OBJECTIVES: The purpose of this study was to examine the prevalence of voice
      disorders in college students and their effect on the students as shown by
      quality-of-life indicators. METHODS: A cross-sectional survey was completed by
      545 college students in 2012. The survey included 10 questions from the Voice
      Related Quality of Life (V-RQOL), selected voice symptoms, and quality-of-life
      indicators of functional health and well-being based on the Short Form 36-item
      Health Survey (SF-36). RESULTS: Twenty-nine percent of the college students (mean
      age, 22.7 years) reported a history of a voice disorder. Hoarseness was the most
      prevalent voice symptom, but was not correlated with V-RQOL scores. A wobbly or
      shaky voice, throat dryness, vocal fatigue, and vocal effort explained a
      significant amount of variance on the social-emotional and physical domains of
      the V-RQOL index (p < 0.05). Voice symptoms limited emotional and physical
      functioning as indicated by SF-36 scores. CONCLUSIONS: Voice disorders
      significantly influence psychosocial and physical functioning in college
      students. These findings have important implications for voice-care services in
      this population.

PMID- 24027862
TI  - End-to-Side interposed donor grafting as a facial nerve reinforcement technique
      after vestibular schwannoma surgery.
AB  - OBJECTIVES: This retrospective case review was performed to determine the facial
      function outcome of an end-to-side interposed donor grafting technique in
      patients who had a nonresponsive and partially injured facial nerve during a
      translabyrinthine approach for vestibular schwannoma resection. METHODS: The
      study included patients with silent electrophysiological tests after partial
      injury of the facial nerve during translabyrinthine schwannoma resection surgery
      in a tertiary referral hospital. The patients underwent end-to-side interposed
      donor grafting as a facial nerve reinforcement technique, and we evaluated their
      facial function after 1 year of follow-up. RESULTS: Four cases with intact
      preoperative facial function were included (3 men and 1 woman). All patients had
      a lack of electrical response from the facial nerve and partial anatomic injury
      after a translabyrinthine approach. An end-to-side interposed donor grafting
      technique was performed. The donor grafts used were the sural nerve (2 patients),
      superior vestibular nerve (1 patient), and greater auricular nerve (1 patient).
      All patients achieved a good House-Brackmann grade. Ocular adjuvant procedures
      were performed in all patients. CONCLUSIONS: Immediate repair of the facial nerve
      with an interposed donor graft may provide better facial function in patients who
      have no electrical response from a partially injured facial nerve after
      vestibular schwannoma surgery.

PMID- 24027863
TI  - Effect on auditory threshold of air and water pockets bordering the pathway
      between soft tissue stimulation sites and the cochlea.
AB  - OBJECTIVES: Auditory sensation can be elicited by applying a bone conduction
      vibrator to skin sites on the head, neck, and thorax over soft tissues. This is
      called soft tissue conduction (STC). We hypothesized that introducing substances
      with acoustic impedances that sharply deviate from those of soft tissues, such as
      air pockets, into the soft tissues beneath soft tissue stimulation sites would
      have an effect on the auditory threshold to stimulation at skin sites over soft
      tissue. METHODS: In human subjects, we assessed the auditory threshold with a
      bone vibrator applied to several STC sites, especially the cheek, and to several
      bone conduction sites on the skull. The subjects were equipped with bilateral
      earplugs. The subject then filled his or her cheek with either air or water, and
      the auditory threshold was again determined. We also recorded the auditory brain
      stem response to STC stimulation under the chin in fat sand rats in the absence
      and presence of subcutaneous air or saline solution pockets (0.4 mL) under the
      chin. RESULTS: In humans, the threshold to stimulation on the cheek was elevated
      (13 to 18 dB) in the presence of an air-inflated cheek, but not with a water
      filled cheek. In animals, in the presence of an air pocket, the auditory brain
      stem response threshold was elevated by 10 to 20 dB; no threshold change occurred
      with a saline solution pocket. CONCLUSIONS: The introduction of air (but not
      water) into the soft tissues beneath the soft tissue stimulation sites led to a
      threshold elevation in both humans and animals. This was not the case when an
      identical volume of water was introduced, which would also have interrupted a
      possible parallel bone conduction pathway. These results provide evidence that
      soft tissue stimulation at low intensities induces tissue vibrations that are
      transmitted to the cochlea along a series of soft tissues with similar acoustic
      impedances.

PMID- 24027864
TI  - Predictors of hearing preservation in the management of labyrinthine fistulas
      positioned on the semicircular canals.
AB  - OBJECTIVES: We sought to identify factors that would predict hearing preservation
      in the treatment of semicircular canal labyrinthine fistulas. METHODS: Between
      1990 and 2010, 97 patients with semicircular canal fistulas were operated on and
      enrolled in this retrospective study. In 62 patients the matrix was removed and
      the fistula was sealed, whereas in 35 patients the canal was drilled, the matrix
      was detached, and the canal was occluded. Perioperative corticosteroids were
      administered in 51 patients. The main outcome measures were the bone conduction
      thresholds evaluated at 1 year after the operation. Factors considered for
      possible association with hearing preservation included age, gender, site and
      size of the fistula, primary versus revision surgery, surgeon, perioperative
      corticosteroid treatment, and surgical management of the fistula. RESULTS: The
      bone conduction hearing level was improved in 16 patients, remained unchanged in
      73 patients, and had worsened in 11 patients. On the univariate analysis, good
      hearing was predicted by grade II fistula, canal plugging, and corticosteroid
      treatment. However, none of these factors attained significance in the logistic
      regression model. CONCLUSIONS: In surgery of semicircular canal fistulas, good
      hearing outcomes are to be expected if perioperative corticosteroids are
      administered, matrix removal and fistula sealing is performed in grade II
      fistulas, and canal occlusion is performed in grade III and IV fistulas.

PMID- 24027865
TI  - Management of upper aerodigestive tract amyloidosis.
AB  - OBJECTIVES: The aim of this study was to discuss the treatment options for upper
      aerodigestive tract amyloidosis. METHODS: Four patients with histologically
      confirmed amyloidosis were included in the study. All patients underwent surgical
      treatment. Three patients had laryngeal amyloidosis, and 1 patient had tonsillar
      amyloidosis. RESULTS: Two of the cases of laryngeal amyloidosis were successfully
      treated with a combination of surgery and radiation therapy. One case of
      laryngeal amyloidosis was treated with surgery alone. The tonsillar amyloidosis
      was removed by tonsillectomy. None of the cases showed systemic involvement. Long
      term follow-up of the patients showed no recurrence or evidence of systemic
      disease. CONCLUSIONS: Surgical resection is the primary treatment for patients
      with upper aerodigestive tract amyloidosis. Radiation therapy is especially
      effective in cases of recurrent amyloidosis with submucosal involvement.
      Pedunculated polypoid lesions may be treated with surgery alone, and in cases of
      recurrence, irradiation following the surgical removal should be considered.
      Tonsillectomy is usually sufficient for treating tonsillar amyloidosis.

PMID- 24027866
TI  - A year in review.

PMID- 24027867
TI  - A working definition of advocacy.

PMID- 24027868
TI  - We remember Tony.

PMID- 24027869
TI  - Touching lives through smiles: Creating one smile at a time.

PMID- 24027870
TI  - The top ten list of things we don't do anymore/the best of now. Part two.

PMID- 24027871
TI  - A gift for discovery: bringing the Gorlin legacy forward.

PMID- 24027872
TI  - Dr. T's Knives.

PMID- 24027873
TI  - U.S., worldwide gold demand 2013.

PMID- 24027874
TI  - Flip of a coin.

PMID- 24027875
TI  - One provider's quality journey.

PMID- 24027876
TI  - The essentials of hospital negotiating.

PMID- 24027877
TI  - MDS 3.0: looking back, looking forward.

PMID- 24027878
TI  - Collaboration improves care.

PMID- 24027879
TI  - Medical professionalism in the 21st century.

PMID- 24027880
TI  - Elder abuse: we are all part of the solution.

PMID- 24027881
TI  - Should we allow insurance auditor access to PHI?

PMID- 24027882
TI  - Doctors in the C-suite: The rewards--and challenges--of being a physician
      executive.

PMID- 24027883
TI  - The Physicians Advocacy Institute: helping physicians face medical audits.

PMID- 24027884
TI  - Healthcare collaboration for the 21st century: direct project.

PMID- 24027885
TI  - Top finance issues for physicians & their practices.

PMID- 24027886
TI  - Renal function recovery in dialysis dependent patients.
AB  - BACKGROUND: Recovery of renal function in patients requiring chronic dialysis is
      an uncommon phenomenon. It is important to identify these patients to avoid
      unnecessary, complicated and expensive dialysis. There are no recognized
      indicators that actually suggest such revival of renal function. The aim of the
      study is to evaluate the indicators of renal recovery in dialysis patients.
      METHODS: It is a retrospective chart review of 299 patients who initiated chronic
      hemodialysis from January 2005 to June 2008. Ninety-eight patients were included
      in the study. Exact logistic regression analysis was used to determine the
      predictors of renal recovery. RESULTS: Ten patients (3%) recovered their renal
      function. All of these patients had an episode of acute deterioration of renal
      function. Renal recovery correlated negatively with baseline serum albumin level
      (r=-0.53, P=<0.0001, age (r=-0.27, P=0.0054) and presence of hypertension (r=
      0.30, P=0.0021) and DM (r=-0.30, P=0.0023) and positively with presence of human
      immunodeficiency virus infection (r=0.23, P=0.02). In multivariable exact
      logistic regression, analysis of low serum albumin level (exact odds ratio [OR]
      27.09, P= 0.0008) and absence of DM (exact OR, 0.048, P=0.0002) were found to be
      the significant predictors of renal recovery. CONCLUSION: It is important to be
      aware of the possibility of renal function recovery in chronic dialysis patients,
      especially in patients who are not diabetic, have episodes of acute renal
      failure, and started on dialysis with low serum albumin level.

PMID- 24027887
TI  - The possible therapeutic benefits of utilizing motion gaming systems on pediatric
      patients presenting autism.
AB  - Autism is a pervasive developmental disorder that affects a growing number of
      children in the United States each year. It is characterized by substantive
      differences in brain structure and function that lead to long-term cognitive and
      social deficits. These differences, combined with the increasing prevalence of
      autism in children, warrant the need for development of innovative, cost
      effective and widely available alternative and complementary therapies. Motion
      gaming has the potential to be highly efficacious as a therapeutic technique to
      aid in developing memory, facial recognition, motor skills and social integration
      in the pediatric autistic population. This paper outlines the major deficits in
      the brains of individuals with autism and describes how the use of motion gaming
      could capitalize on the individual strengths of each patient, leading to
      improvements in a variety of deficits.

PMID- 24027888
TI  - Take a lesson from Tulsa.

PMID- 24027889
TI  - Sweet dreams.

PMID- 24027890
TI  - The perfect imperfect appointment.

PMID- 24027891
TI  - Practice management curriculum in New York State dental schools.
AB  - The practice management curricula of the four dental schools in New York State
      were examined and were found to be limited. Although it was acknowledged that it
      is challenging to expand the hours devoted to teaching this discipline, steps
      should be taken to address the issue. The author suggests two initiatives that
      can help address this deficiency.

PMID- 24027892
TI  - What you need to know about the Affordable Care Act in New York.

PMID- 24027893
TI  - A conversation with NYSDA President Joel M. Friedman, D.D.S.

PMID- 24027894
TI  - Big easy beckons. ADA Annual Session on tap for October.

PMID- 24027895
TI  - Child abuse: concerns for oral health practitioners.
AB  - Child abuse and neglect are prevalent issues that permeate all ethnic, cultural
      and socioeconomic segments of society. Parents of abused children frequently
      change physicians in order to prevent detection, but they are more likely to
      continue to visit the child's dentist. Most states recognize four major types of
      maltreatment: neglect; physical abuse; psychological maltreatment; and sexual
      abuse. The American Academy of Pediatric Dentistry defines dental neglect as "the
      willful failure of parent or guardian to seek and follow through with treatment
      necessary to ensure a level of oral health essential for adequate function and
      freedom from pain and infection." The oral health practitioner must uphold his or
      her legal and ethical responsibility if there is suspicion, record and report the
      incidence. It may help save a child from further abuse.

PMID- 24027896
TI  - Single tooth odontodysplasia. Case report.
AB  - Odontodysplasia (ghost tooth) is an uncommon, nonhereditary developmental
      condition of unknown origin, affecting both mesodermal and ectodermal elements of
      the dental organ. To our knowledge, this case is unique in that it is only the
      second reported case of odontodysplasia affecting a single tooth. Based on
      clinical, radiographic and histologic findings, we diagnosed this tooth as a
      ghost tooth.

PMID- 24027897
TI  - Titanium hypersensitivity. A hidden threat for dental implant patients?
AB  - Titanium and its alloys have been widely used for dental prosthetic devices
      because of their superior mechanical properties and biocompatibility. However,
      the incidence of titanium hypersensitivity or allergy is still unknown and the
      discussion about its existence is ongoing. Unexplained implant failures have also
      forced dental clinicians to investigate the possibility of titanium
      hypersensitivity or allergy. This review focuses on the potential of dental
      implant-related titanium hypersensitivity or allergic reactions. It includes an
      examination of the existing scientific literature and current knowledge. Evidence
      based data and studies related to titanium hypersensitivity in dental implant
      patients are also discussed.

PMID- 24027898
TI  - Pleomorphic adenoma of the palate in a child.
AB  - Presented is a pleomorphic adenoma of the palate in a 12-year-old boy.
      Pleomorphic adenoma is usually found in adults and is rarely found in patients
      under 20 years of age. We present initial exam, diagnosis, treatment and a review
      of literature.

PMID- 24027899
TI  - Even small interventions can improve oral health.
AB  - When resources are scarce, authors of articles appearing in health publications
      have questioned the effectiveness of traditional interventions as a means of
      improving oral health. The experience in Delicias, Honduras, indicates that the
      principles of BPOC (Basic Package of Oral Care) may provide quicker and better
      results.

PMID- 24027900
TI  - Carcinoma ex pleomorphic adenoma. Case report.
AB  - Carcinoma ex pleomorphic adenoma (CXPA) is a rare and aggressive malignancy that
      usually develops in primary or recurrent pleomorphic adenoma. It occurs in 6% of
      all pleomorphic adenomas, of which only 7% of cases occur in minor salivary gland
      tumors. The rate of occurrence and malignant change increases with time if a case
      is left untreated. Intraorally, it is mostly seen in the palate, followed by the
      upper lip and buccal mucosa. CXPA of the hard palate typically presents as a
      painless, slow-growing swelling that frequently involves the periosteum and
      underlying palatal bone. Imaging of CXPA is usually noncontributory, leading to
      frequent misdiagnosis. Longstanding cases may extend up to the parapharyngeal
      space and cavernous sinus. We describe a rare case of CXPA of the palate with non
      significant clinical and radiological findings. Early diagnosis for better
      prognosis is stressed.

PMID- 24027901
TI  - Management of oral pyogenic granuloma with sodium tetra decyl sulphate. A case
      series.
AB  - Pyogenic granuloma, or granuloma pyogenicum, is a common, tumor-like growth of
      the oral cavity or skin that is considered to be an exaggerated, localized
      connective tissue reaction to a minor injury or irritation. A total of five
      clinical cases of oral pyogenic granuloma were randomly selected in the age group
      between 26 and 41 years. All these cases were treated with sodium tetra decyl
      sulphate and examined for regression and reccurrence of the lesion for six
      months. Various treatment modalities consist of conservative surgical excision,
      cryosurgery, laser surgery and sclerotherapy. Sclerotherapy with sodium tetra
      decyl sulphate is a relatively simple and effective method for treating oral
      pyogenic granuloma.

PMID- 24027902
TI  - Are you ready for new prescription requirements?

PMID- 24027903
TI  - [Growth and biochemical composition of thalassiosira pseudonana
      (Thalassiosirales: Thalassiosiraceae) cultivated in semicontinuous system at
      different culture media and irradiances].
AB  - Thalassiosira pseudonana is a marine Bacillariophyta commonly used as live feed
      in mariculture. The growth rate and biochemical composition of microalgae are
      highly influenced by environmental factors such as, irradiance and nutrient
      availability. The aim of this study was to investigate the influence of three
      irradiances (60, 120 and 180 microE/m2.s) and two culture media (Algal and Humus)
      on growth and biochemical composition of this diatom. The microalga was grown
      semicontinuously at a daily renewal rate of fresh media of 30%, 37 per thousand
      salinity, 25 +/- 1 degree C and constant aeration (200 mL/min). The cell
      densities (cel/mL) and contents of protein, lipid, carbohydrate, chlorophyll a,
      total carotenoids, and fatty acids, showed significant differences (p < 0.05)
      between treatments. During steady-state phase, the maximal cell density, and
      lipid and carbohydrate contents were of 4.62 x 10(6) cel/mL, 20.3 +/- 2.28% and
      16.6 +/- 2.43%, respectively, and were achieved in Humus medium at 180 microE/
      m2.s. Moreover, highest protein contents (45.0 +/- 5.05%) and total carotenoids
      (0.5 +/- 0.01%) were obtained in Algal medium at 180 microE/m2.s. Chlorophyll a
      (0.93 +/- 0.04%) was higher at low irradiances in Algal medium. In both media,
      the fatty acids unsaturation degree was lower with increasing irradiance, being
      eicosapentaenoic acid, 20:5 n-3 (EPA) most represented (6.20%) in Algal medium at
      60 microE/m2.s. This strain of T. pseudonana showed multiple physiological
      responses to changes in culture conditions, and may be cultivated with an
      alternative medium, which reduced the operating costs and allowed a high
      nutritional biomass production value for animals under culture.

PMID- 24027904
TI  - Crouania pumila sp. nov. (Callithamniaceae: Rhodophyta), a new species of marine
      red algae from the Seaflower International Biosphere Reserve, Caribbean Colombia.
AB  - In the Colombian Caribbean, the marine macroalgal flora of the Seaflower
      International Biosphere Reserve has been little studied, despite its ecological
      importance. Historical records have reported only 201 macroalgae species within
      its area of almost 350,000 km2. However, recent surveys have shown a diversity of
      small algae previously overlooked. With the aim to determine the macroalgal
      diversity in the Reserve, we undertook field surveys in different ecosystems:
      coral reefs, seagrass beds, and rocky and sandy substrates, at different depths,
      from intertidal to 37 m. During these field surveys, we collected a small
      described species belonging to the genus Crouania (Callithamniaceae, Rhodophyta),
      Crouania pumila sp. nov. that is decribed in this paper. This new species was
      distinguished from other species of the genus by a distinctive suite of traits
      including its diminutive size (to only 3.5 mm in length), its decumbent, slightly
      calcified habit (epiphytic on other algae), its ramisympodial branching, the
      ecorticate main axes, and the elongate shape of the terminal cells of the
      cortical filaments. The observations were provided for both female (cystocarpic)
      and tetrasporangiate thalli; however, male thalli were not seen. Further studies
      have to be undertaken in this Reserve in order to carry out other macroalgal
      analysis and descriptions.

PMID- 24027905
TI  - [Anatomic characterization of growth-rings in 80 potential tree species for
      dendrocronological studies in the Central Forest, Peru].
AB  - The knowledge about the existence of annual tree rings in tropical trees, which
      was already found at the beginning of the last century, was ignored by many
      scientists for a long time. Wood samples of 80 tree species from seven different
      sites belonging to Satipo and Chanchamayo provinces in Central Forest, Peru. Wood
      slices were taken at 1.30 m height, following the Peruvian Technical Norms (NTP)
      251-008, COPANT norms 30:1-019 and IAWA (1989). Results showed that 24 of the 80
      tree species analyzed showed a potential for dendrocronological studies, 25 had
      problems for growth-rings analysis, and 31 did not have potential. The problems
      most frequently found were: barely visible or irregular ring growth, parenchyma
      bands and multiseriate rays difficult to be identified in rings growth. The "T"
      Student test showed that the significant variation in vessel and fiber diameters
      between growth zones (Early-wood and late-wood) of species with potential for
      dendrocronology, do have a periodic cells production, so is possible to suggest
      the annual formation of each growth-ring. However, those species without
      potential to dendrocronology may be influenced by of a lot of factors, such as
      biotic and abiotic conditions of environment, as well as the genetic aspect of
      each species.

PMID- 24027906
TI  - [Casuarina equisetifolia (Casuarinaceae) growth in soil with diesel and
      application of biostimulation and bioaugmentation].
AB  - Phytoremediation is an ecologically sound biotechnology directed to cleaning up
      contaminated soils. The study of tree species to treat petroleum contaminated
      soils is scarce; moreover, the combination of phytoremediation with
      bioaugmentation and biostimulation processes is also limited. Thus, this work
      evaluated the effects of the inoculation of Glomus intraradices, a bacterial
      consortium (M2BOS1-R2 and M2BOSI-F4) and Trichoderma viride, on the growth of
      Casuarina equisetifolia, fertilized with Floranid or Triple 17, when sown in a
      diesel-contaminated soil (7 500mg/kg). The factorial experiment 2x5x3 included 30
      treatments with 10 replicates in a completely randomized design under greenhouse
      conditions for 120 days. Diesel significantly diminished plant height, total
      biomass, and plant index quality (PIQ). Glomus or bacterial consortium
      significantly increased plant height, total biomass and PIQ when compared to the
      inoculation of the three microorganisms or to the control. Floranid had negative
      effects on plant growth and PIQ at diesel contamination. Fertilization with
      Triple 17 combined with the three microorganisms stimulated plant growth in the
      absence of diesel, whereas in the presence of this contaminant the treatments
      combining Triple 17 with the bacterial consortium or with Trichoderma had better
      plant growth and PIQ. Mycorrhizal colonization was inhibited due to diesel
      contamination, and especially when Floranid was applied. The fertilizer Triple 17
      (biostimulation) combined with the beneficial microorganisms (bioaugmentation)
      improved growth responses of C. equisetifolia in diesel-contaminated soil.

PMID- 24027907
TI  - Structural adaptations of two sympatric epiphytic orchids (Orchidaceae) to a
      cloudy forest environment in rocky outcrops of Southeast Brazil.
AB  - The survival of plants in epiphytic environments depends on vegetative
      adaptations capable to defraud different stresses. Based on the structural
      diversity of the Orchidaceae, the current study has the objective of relating the
      anatomical structure of Dichaea cogniauxiana and Epidendrum secundum with the
      distinct environments where they live. It was expected that, despite structural
      similarities as strategies for resource acquisition, some peculiar variations
      related to the distinct light microenvironments (inside or in the edge of the
      nebular forest, near to "campo rupestre" area) might be found. Leaves and roots
      of both species were collected in a nebular forest located at a "campo rupestre"
      area at Serra da Piedade, Brazil), in January and February 2005. D. cogniauxiana
      is adhered to trunks, in sites with high atmospheric humidity and shaded, while
      E. secundum is located at the edge of the nebular forest, in more luminous sites.
      The leaves of E. secundum had thicker cuticle and higher number of stomata per
      area than those of D. cogniauxiana, characteristics coherent with their distinct
      pattern of exhibition to sun light. The suprastomatic chambers formed by the
      thicker cuticle may function as a barrier of resistance to water evaporation. The
      succulence of the leaves of E. secundum propitiates organic acids storage at
      night, and the storage of starch may be involved in PEP-carboxylase metabolism,
      both propitiating CAM mechanism. Roots with larger number of cell layers of the
      velamen, and specialized thick walled cortical cells (both in E. secundum) help
      water absorption and indicate better adaptation to an environment with intense
      solar radiation and a probable higher water deficit. The remarkable cell wall
      thickening of E. secundum exodermis can confer more efficient protection against
      the excess of transpiration at the border of the nebular forest. On the other
      hand, besides D. cogniauxiana be epiphyte, it is in a low position - in a shaded
      environment and with high relative humidity. Its thin thickened velamen permits
      the entrance of the low available light, and photosynthesis, producing oxygen and
      helping to avoid hypoxia condition. As features registered for D. cogniauxiana
      and E. secundum roots, we can depict the velamen, distinct exodermis and
      endodermis, and specialized thick walled cortical cells as characteristic of
      epiphytic plants.

PMID- 24027908
TI  - [Sporogenesis and spores of Equisetum bogotense (Equisetaceae) from mountain
      areas of Colombia].
AB  - Studies on some reproductive traits in Equisetum species are scarce and valuable
      to understand species distribution. Therefore, a detailed study of the
      sporogenesis process and spore development in E. bogotense is presented, with an
      analysis of the main events during meiosis, maturation of spores, spore wall
      ultrastructure, orbicules and elaters. Specimens were collected from 500 to 4500
      m in Cauca, Colombia. Strobili at different maturation stages were fixed,
      dehydrated, embedded in resin, and ultra-microtome obtained sections were stained
      with Toluidine blue. Observations were made with optical microscopy with
      differential interference contrast illumination technique (DIC), transmission and
      scanning electron microscopy (TEM and SEM). Ultrathin sections (70-80 microm) for
      TEM observations were stained with uranyl acetate and lead citrate; while samples
      for SEM observations, were fixed, dehydrated in 2.2-dimethoxypropane and dried at
      critical point as in standard methods. Strobili have numerous mature
      sporangiophores, each one with a peltate structure, the scutellum, bearing five
      six sessile sporangia attached to the axis of strobilus by the manubrium.
      Immature sporocytes (spore mother cells) are tightly packed within the young
      sporangia. The sporocytes quickly undergo meiosis, by passing the stage of
      archesporium and give origin to tetrads of spores. The tapetum loses histological
      integrity during early stages of sporogenesis, intrudes as a plasmodial mass into
      the cavity of the sporangium, partially surrounding premeiotic sporocytes, and
      then, tetrads and adult spores. The tapetum disintegrates towards the end of the
      sporogenesis, leaving spores free within the sporangial cavity. Spores present
      several cytological changes that allow them to achieve greater size and increase
      the number of plastids, before reaching the adult stage. Sporoderm includes three
      layers external to the cytoplasmic membrane of the spore cell, and they are
      pseudoendospore, exospore and perispore. Viewed with SEM, the exospore is smooth
      to rugulate, with micro perforations, while the perispore is muriform, rugate,
      with narrow, delicate, discontinuous, randomly distributed folds delimiting
      incomplete, irregular areolae, externally covered by of different size, densely
      distributed orbicules. These orbicules are also found all over the external face
      and margins of the elaters, while the internal face is smooth and lack orbicules.
      Viewed with TEM, the exospore is a thick layer of fine granular material, while
      perispore is a thinner layer of dense, separate orbicules. The elaters are
      composed by two layers of fibrillar material: an inner layer with longitudinally
      oriented fibrils and an outer, thicker and less dense layer with fibrils
      transversely fibrils and abundant, external orbicules. It is suggested that the
      processes of ontogeny and characters of the sporoderm are relatively constant in
      Equisetum; however, sporogenesis in E. bogotense is synchronous and this
      condition has been observed so far only in E. giganteum, a tropical genus also
      found in Colombia.

PMID- 24027909
TI  - Plant regeneration from callus cultures of Vitex trifolia (Lamiales: Lamiaceae):
      a potential medicinal plant.
AB  - Vitex trifolia is a shrub species with popular use as a medicinal plant, for
      which leaves, roots and flowers have been reported to heal different distresses.
      The increasing exploitation of these plants has endangered its conservation, and
      has importantly justified the use of biotechnological tools for their
      propagation. Our aim was to present an efficient protocol for plant regeneration
      through organogenesis; and simultaneously, to analyze the genetic homogeneity of
      the established clonal lines by Randomly Amplified Polymorphic DNA (RAPD) and
      Inter Simple Sequence Repeat (ISSR) markers. Plantlet regeneration was achieved
      in callus cultures derived from stem, leaf and petiole explants of V. trifolia on
      a differently supplemented Murashige & Skoog medium, and incubated at 25 +/-2
      degrees C under a light intensity of 61 micromol/m2s from cool white fluorescent
      lamps and a 16 h photoperiod. The rate of shoot bud regeneration was positively
      correlated with the concentration of hormones in the nutrient media. Shoot buds
      regenerated more rapidly from stem and petiole explants as compared to leaf
      explants on medium containing 11.10 microM BAP in combination with 0.54
      microMNAA. Addition of 135.74-271.50 microM adenine sulphate (Ads) and 0.72-1.44
      microM gibberellic acid (GA3) to the culture medium increased the growth of shoot
      buds. The highest rate of shoot bud regeneration responses was obtained in stem
      explants using 11.10 microM BAP in combination with 0.54 microM NAA, 271.50
      microM Ads and 1.44 microM GA3. In vitro rooting of the differentiated shoots was
      achieved in media containing 1.23 microM indole butyric acid (IBA) with 2% (w/v)
      sucrose. Regenerated plantlets were successfully established in soil with 86%
      survival under field condition. Randomly Amplified Polymorphic DNA and Inter
      Simple Sequence Repeat markers analyses have confirmed the genetic uniformity of
      the regenerated plantlets derived from the second up to fifth subcultures. This
      protocol may help in mass propagation and conservation of this important
      medicinal plant of great therapeutic potential.

PMID- 24027910
TI  - Establishment of cell suspension cultures of two Costa Rican Jatropha species
      (Euphorbiaceae).
AB  - J. curcas has been studied in different countries and some interesting agronomic,
      pharmacological and industrial properties have been reported. More recently, it
      has been considered an important alternative source for biofuel production. The
      objective of this study was to establish a long-term method for the maintenance
      of calli and cell suspension cultures of the local species J. curcas and J.
      gossypifolia, in order to allow future studies for novel compounds with
      pharmaceutical or industrial applications. For this, friable calli were
      successfully induced from hypocotyl segments of.. curcas and J. gossypifolia that
      were cultured in semisolid MS media supplemented with 1.5 mg/L, and 0.5 mg/L of
      2,4-D, respectively. Cell suspension cultures of J. curcas were established using
      1 g of 35 and 60-day calli, in 50 mL of liquid MS media supplied with 1.5 mg/L of
      2,4-D; sucrose and maltose were additionally evaluated as carbon sources. After
      35 days, cell suspension cultures initiated with 35-day calli, showed greater
      cell growth with a maximum biomass of 194.9 g/L fresh weight, 6.59 g/L dry weight
      and 17.3% packed volume. The exponential phase ended at day 35 for cultures
      initiated with 35-day calli, and at day 21 for cultures initiated with 60-day
      calli. Higher biomass production was obtained with sucrose. Cell cultures were
      established with 35-day calli in MS media with the same 2,4-D concentration used
      for calli induction and 30g/L sucrose. This medium was considered optimum for the
      maintenance and growth of cell suspensions for both species, with sub-cultures
      every 20 days. The biotechnological potential for the production of bioactive
      compounds in these species for pharmacological, agricultural and industrial
      applications is being evaluated.

PMID- 24027911
TI  - Morpho-anatomy, imbibition, viability and germination of the seed of
      Anadenanthera colubrina var. cebil (Fabaceae).
AB  - Seed biology is a relevant aspect of tropical forests because it is central to
      the understanding of processes of plant establishment, succession and natural
      regeneration. Anadenanthera colubrina var. cebil is a timber tree from South
      America that produces large seeds with thin weak teguments, which is uncommon
      among legumes. This study describes the morphology and anatomy of the seed coat,
      the viability, imbibition, and germination in this species. Seeds used during the
      essays came from 10 trees that grow naturally in Horco Molle, province of
      Tucuman, Argentina. Seed morphology was described from a sample of 20 units. The
      seed coat surface was examined with a scanning electron microscope. Transverse
      sections of hydrated and non-hydrated seeds were employed to describe the
      histological structure of the seed coat. Hydration, viability and germination
      experiments were performed under laboratory controlled conditions; and the
      experimental design consisted of 10 replicas of 10 seeds each. Viability and
      germination tests were conducted using freshly fallen seeds and seeds stored for
      five months. Morphologically the seeds of A. colubrina var. cebil are circular to
      subcircular, laterally compressed, smooth, bright brown and have a horseshoe
      fissure line (= pleurogram) on both sides. The seed coat comprises five tissue
      layers and a double (external and internal) cuticle. The outer cuticle (on the
      epidermis) is smooth and interrupted by microcracks and pores of variable depth.
      The epidermis consists of macroesclereids with non-lignified secondary walls.
      This layer is separated from the underlying ones during seed hydration. The other
      layers of internal tissues are comprised of osteosclereids, parenchyma,
      osteosclereids, and macrosclereids. The percentage of viable seeds was 93%,
      decreasing to 75% in seeds with five months old. Seed mass increased 76% after
      the first eight hours of hydration. Germination percentage was 75% after 76
      hours. Germination of seeds stored for five months decreased to 12%. The results
      showed that seeds of A. colubrina var. cebil are highly permeable and germinate
      directly without a dormant period.

PMID- 24027912
TI  - [State strategy for Cycad (Zamiaceae) conservation: a proposal for the State of
      Hidalgo, Mexico].
AB  - Mexico has the second largest cycad diversity in the world, and the Sierra Madre
      Oriental (SMO) is one of the richest biogeographic regions for these plants.
      Despite there is a general Cycad National Program in the country, there are no
      state-level cycad conservation strategies or programs. Thus the aim of this study
      was to propose a cycad conservation strategy for the state of Hidalgo, which is
      located in the Southern part of the SMO. For this, a cycad species inventory was
      made in the state, for which three methods were used: review of published
      literature; consultation in the main Mexican herbaria to verify botanical
      specimens; and exhaustive field research to compare findings with previously
      reported species and to recognize new records at the county and state level. The
      proposed research work strategy combined the following elements: prioritize the
      county and local areas with greatest cycad species richness; prioritize the
      species least resistant to environmental change and/or having restricted
      geographic distribution; and to consider the main uses of these plants by local
      residents. The results showed that Hidalgo has three genera and eight species
      ofcycads: Ceratozamia fuscoviridis, C. latifolia, C. mexicana, C. sabatoi, Dioon
      edule, Zamia fischeri, Z. loddigesii and Z. vazquezii, all of which are
      considered by the International Union for Conservation of Nature (IUCN). This
      study added two new species records for Hidalgo and 21 at the county level. The
      species are distributed in 26 counties, of which Chapulhuacan and Pisaflores are
      notable for their high species richness. Hidalgo has the fourth-greatest cycad
      species richness among Mexican states, although its area accounts for only 1.07%
      of the country. The state's diversity is greater than in other states with larger
      area, and even than in some other entire countries in Mesoamerica. The presented
      state cycad conservation strategy proposes that a total of some 11,325 ha to be
      conserved in nine zones, including different vegetation types, distributed in
      seven counties. The strategy involves a mixed scheme that incorporates
      conservation in Protected Natural Areas (ANP), Small Farmer Reserves (Reservas
      Campesinas) and Environmental Management Units (UMA in Spanish). This proposal
      will be useful for government agencies to take into account in the process of
      designating land use for the Cloud Forest Biological Corridor (CBBMM in Spanish),
      a ANP in creation. The state of Hidalgo urgently needs a detailed analysis of
      trends in changes in vegetation cover and land use, and demographic studies of
      the cycads. It is recommended that the implementation phase of this state
      strategy be carried out jointly with local communities, academia, and state and
      federal agencies responsible for biodiversity conservation.

PMID- 24027913
TI  - Identification of endangered or threatened Costa Rican tree species by wood
      anatomy and fluorescence activity.
AB  - A total of 45 native Costa Rican tree species are threatened or in danger of
      extinction, but the Convention on International Trade Endangered Species (CITES)
      includes only eight of these in its Appendices. However, the identification of
      other species based on their wood anatomy is limited. The present study objective
      was to describe and to compare wood anatomy and fluorescence activity in some
      endangered or threatened species of Costa Rica. A total of 45 (22 endangered and
      23 threatened with extinction) wood samples of these species, from the xylaria of
      the Instituto Tecnologico de Costa Rica and the Forest Products Laboratory in
      Madison, Wisconsin, were examined. Surface fluorescence was positive in eight
      species, water extract fluorescence was positive in six species and ethanol
      extract fluorescence was positive in 24 species. Almost all species were diffuse
      porous except for occasional (Cedrela odorata, C. fissilis, Cordia gerascanthus)
      or regular (C. salvadorensis and C. tonduzii) semi-ring porosity. A dendritic
      vessel arrangement was found in Sideroxylon capari, and pores were solitary in
      Guaiacum sanctum and Vantanea barbourii. Vessel element length was shortest in
      Guaiacum sanctum and longest in Humiriastrum guianensis, Minquartia guianensis
      and Vantanea barbourii. Finally, anatomical information and fluorescence activity
      were utilized to construct an identification key of species, in which
      fluorescence is a feature used in identification.

PMID- 24027914
TI  - Species composition and bathymetric distribution of gorgonians (Anthozoa:
      Octocorallia) on the Southern Mexican Pacific coast.
AB  - Gorgonians are important components of coastal ecosystems, as they provide
      niches, natural compounds with medical applications and are used as
      bioindicators. Species composition and assemblage structure of gorgonians
      (Anthozoa: Octocorallia) were studied along a bathymetric profile in the Southern
      Mexican Pacific coast. Species composition was based on specimens collected
      within a depth range of 0-70 m in 15 sites. The relative abundance of species was
      determined in six sites at four depths (5, 10, 20 and 25 m) using three 10 m2
      transects at each depth level. Twenty-seven species of gorgonians belonging to
      six genera and three families were registered. The species composition varied
      with depth: 11 species were distributed between 0-25m depth, while 17 species
      were found between 40-70 m depth interval. The shallow zone is characterized by a
      relatively large abundance of gorgonians, dominated by colonies of Leptogorgia
      cuspidata and L. ena. In contrast, the deepest zone was characterized by
      relatively low abundance of gorgonians, dominated by L. alba, the only species
      observed in both depth intervals. The similarity analysis showed differences in
      the composition and abundance of species by depth and site, suggesting that the
      main factor in determining the assemblage structure is depth. Results of this
      study suggest that the highest richness of gorgonian species in the study area
      may be located at depths of 40-70 m, whereas the highest abundances are found
      between 5 and 10 m depth. This study represents a contribution to the poorly
      known eastern Pacific gorgonian biota.

PMID- 24027915
TI  - [Individual growth modeling of the penshell Atrina maura (Bivalvia: Pinnidae)
      using a multi model inference approach].
AB  - Growth models of marine animals, for fisheries and/or aquaculture purposes, are
      based on the popular von Bertalanffy model. This tool is mostly used because its
      parameters are used to evaluate other fisheries models, such as yield per
      recruit; nevertheless, there are other alternatives (such as Gompertz, Logistic,
      Schnute) not yet used by fishery scientists, that may result useful depending on
      the studied species. The penshell Atrina maura, has been studied for fisheries or
      aquaculture supplies, but its individual growth has not yet been studied before.
      The aim of this study was to model the absolute growth of the penshell A. maura
      using length-age data. For this, five models were assessed to obtain growth
      parameters: von Bertalanffy, Gompertz, Logistic, Schnute case 1 and Schnute and
      Richards. The criterion used to select the best models was the Akaike information
      criterion, as well as the residual squared sum and R2 adjusted. To get the
      average asymptotic length, the multi model inference approach was used. According
      to Akaike information criteria, the Gompertz model better described the absolute
      growth of A. maura. Following the multi model inference approach the average
      asymptotic shell length was 218.9 mm (IC 212.3-225.5) of shell length. I
      concluded that the use of the multi model approach and the Akaike information
      criteria represented the most robust method for growth parameter estimation of A.
      maura and the von Bertalanffy growth model should not be selected a priori as the
      true model to obtain the absolute growth in bivalve mollusks like in the studied
      species in this paper.

PMID- 24027916
TI  - A ten-month diseases survey on wild Litopenaeus setiferus (Decapoda: Penaeidae)
      from Southern Gulf of Mexico.
AB  - The development of shrimp aquaculture in Mexican coasts of the Gulf of Mexico
      began to be explored using the Pacific white shrimp Litopenaeus vannamei in the
      mid 90's. Many concerns over the risk of disease transmission to the economically
      important native penaeids, have been the main deterrent for the aquaculture of L.
      vannamei in the region. Concurrently, more than 10 years of research experience
      on the aquaculture suitability of the native Litopenaeus setiferus from the
      Terminos Lagoon, in the Yucatan Peninsula, have been accumulated. The aim of this
      study was then to determine the seasonal variations of the naturally acquired
      diseases and the possible detection of exotic pathogens. For this, random
      subsamples (n-60) of juveniles L. setiferus were collected from monthly captures.
      In order to detect the widest range of pathogens, including infectious hypodermal
      and hematopoietic necrosis (IHHNV) and white spot syndrome (WSSV) viruses, both
      histopathological and molecular methods were employed. Monthly prevalence (%) was
      calculated for every finding. We were able to detect a total of 16 distinct
      histological anomalies, most of which the presumptive aetiological agent was
      readily identified. PCR results for viruses were negative. For some pathogens and
      symbionts, the prevalence was significantly different between the adult and
      juvenile populations. Prevalence of diseases tended to be higher in juvenile
      shrimp than in adults. The results of this study indicated that L. setiferus
      carry a wide variety of pathogens and symbionts that seem to be endemic to
      penaeids of the Gulf of Mexico, and those juveniles were more conspicuous to
      acquire pathogens and symbionts than adults.

PMID- 24027917
TI  - [Length of capture and reproduction of green spiny lobster panulirus gracilis
      (Decapoda: Palinuridae) from the coast of Manabi, Ecuador].
AB  - Green spiny lobster Panulirus gracilis is an economical resource of high
      importance for fishermen populations in the continental coast of Ecuador.
      Traditionally, this specie is captured using gillnets and semiautonomous diving
      system (hookah). With the objective to analyze some biological aspects about this
      fishery in Manabi, we examined lengths of capture (carapace length: CL and
      abdominal length: AL), sex ratio and reproductive aspects in females between June
      and September 2010. A total of 415 females and 288 males were captured with
      gillnets in El Mangle-Puerto Cayo (Central coast, depth: 3-6 m), and by diving in
      Puerto Lopez-Salango (South coast, depth: 7-12 m). Sex ratio from males to
      females was 0.72:1 for gillnets, and 0.63:1 for diving. Lobsters captured by
      diving were larger (84.1 +/- 3.3 mm CL) than lobsters captured by gillnets (73.4
      +/- 2.9 mm CL). Percentage of ovigerous females captured by diving was higher
      than females captured by gillnets. There was a pattern between lengths by sex
      (relation AL vs. CL); females were larger than males at same CL. Differences
      found between lengths and the occurrence of ovigerous females could be related
      with depth where capture methods are used. A total of 98% of landed lobsters were
      smaller than legal captured length and we recommend the establishment of a
      monitoring evaluation program during the fishing season, and a ban, in order to
      evaluate the natural fluctuation in length and reproductive stages of green spiny
      lobster in the coasts of Manabi.

PMID- 24027918
TI  - Apparent carbohydrate and lipid digestibility of feeds for whiteleg shrimp,
      Litopenaeus vannamei (Decapoda: Penaeidae), cultivated at different salinities.
AB  - Whiteleg shrimp, Litopenaeus vannamei is one of the most commercially farmed
      species worldwide because of its fast growth, good survival rate at high farming
      densities, and osmoregulatory capacity, which makes it an excellent candidate for
      cultures at different salinities. The knowledge of shrimp nutritional
      requirements is critical in the formulation of diets to allow optimal growth at
      different environmental conditions and development stages. The effect of salinity
      on apparent digestibility of shrimp feed is not well known, and this information
      is required in shrimp diet formulation. For this purpose, the apparent
      digestibility coefficients of carbohydrates (ACD) and lipids (ALD) were
      determined for juvenile whiteleg shrimps under controlled culture conditions. We
      evaluated the apparent digestibility of six commercial (D1:37CP, D2:38CP,
      D3:39CP, D4:34CP, D5:35CP, and D6:37CP) and two experimental (E1:33CP and
      E2:33CP) diets for juvenile whiteleg shrimp cultivated at three salinities (5, 35
      and 50 psu) in 60 L aquariums. ACD and ALD were determined in vivo using chromic
      oxide as an inert marker. Our results showed that ALD in most cases was over 80%,
      independent of salinity, except the E1:33CP diet which had 74.0% at 50 psu. Diet
      D3:39CP showed the highest ALD coefficient (90.1 and 90.6% at 5 and 35 psu,
      respectively). For ACD, differences were detected between commercial and
      experimental diets at every salinity level, although salinity effect on ACD was
      not significant. Diet D4:34CP had the highest coefficient (92.4%) at 5 psu, and
      E2:33CP at 35 and 50 psu (97.3 and 94.7%). This study demonstrated that there is
      no significant effect of saline variations on carbohydrate and lipid
      digestibility by juvenile whiteleg shrimp, under the experimental conditions.

PMID- 24027919
TI  - [Microorganisms effect with probiotic potential in water quality and growth of
      the shrimp Litopenaeus vannamei (Decapoda: Penaeidae) in intensive culture].
AB  - The use of probiotics has gained acceptance in aquaculture, particularly in
      maintaining water quality and enhancing growth in organisms. This study analyzed
      the effect of the commercial (EM, Japan) natural product composed by
      (Rhodopseudomonas palustris, Lactobacillus plantarum, Lactobacillus casei and
      Saccharomyces cerevisiae) added to the water, in order to determine its effect in
      water quality, sediment and growth of L. vannamei under intensive culture. The
      evaluation included three treatments with a weekly addition of EM: i) tanks
      without probiotics (C), ii) tanks with a dose of 4 L/ha (EM1) and iii) tanks with
      a dose of 10 L/ha (EM2). The treatment C was carried out three times, while
      treatments EM1 and EM2 were carried out four times. A total of 4 350 shrimps were
      measured for total length and weight, to calculate total and porcentual weight
      gain, daily weight gain, specific growth rate (TCE), and food conversion factor
      (FCA); besides, the survival rate was estimated. The use of probiotics allowed a
      shorter harvest time in treatments EM1 (90 d) and EM2 (105 d) with relation to
      the treatment C (120d). Treatments EM1 and EM2 were within the recommended
      intervals for culture, with respect to treatment C. The use of probiotic bacteria
      significantly regulated pH (EM1, 8.03 +/- 0.33; EM2, 7.77 +/- 0.22; C, 9.08 +/-
      0.35) and reduced nitrate concentration (EM1, 0.64 +/- 0.25 mg/L; EM2, 0.39 +/-
      0.26 mg/L; C, 0.71 mg/L). Water pH mostly explained the variance with respect to
      the treatments. Treatment EM2 presented the greatest removal of organic matter
      (1.77 +/- 0.45%), whereas the contents of extractable phosphorus increased
      significantly in treatment EM1 with 21.6 +/- 7.99 mg/kg and in treatment EM2 with
      21.6 +/- 8.45 mg/kg with control relation (14.3 +/- 5.47). The shrimp growth was
      influenced by dissolved oxygen, salinity and pH in the sediment, establishing
      that salinity was the most important variable in the weight with a negative
      association. Treatment EM1 recorded an improved TCE (2.69 +/- 0.35%/d) and FCA
      (1.46 +/- 0.20) with relation to the control treatment (TCE, 1.88 +/- 0.25%/d;
      FCA, 2.13 +/- 0.48). Survival was significantly greater in treatments containing
      probiotics with 61 +/- 8.76% and 60 +/- 10.5% for EM1 and EM2, respectively. This
      study indicated the positive effect obtained with the use of this commercial
      probiotic, to improve culture conditions and growth parameters in an intensive
      culture of L. vannamei.

PMID- 24027920
TI  - [Community structure of sponges (Porifera) in three reefs at Morrocoy National
      Park, Venezuela and its correspondence with some environmental variables].
AB  - Sponges have an important ecological role in coral reef ecosystems. However, when
      compared to other benthic Phyla, it has been little researched. This research was
      focused in the variability of the community structure of sponges in three
      locations at Morrocoy National Park (Cayo Sombrero, Playa Mero and Punta Brava)
      exposed to different environmental conditions (transparency and currents
      intensity) and affected in different degree of severity by a mass mortality event
      in 1996. A total of 15 transects (10 m long and 1 m wide) were evaluated in three
      strata (between 3 and 15 m depth) in each site, where all the individuals were
      counted by species. Relative abundance by species, diversity and evenness were
      calculated. Locations showed differences respect turbidity, wave and current
      intensity. 27 species were found in Morrocoy; Cayo Sombrero (23), Playa Mero (18)
      and Punta Brava (15). Agelas sceptrum, Amphimedon erina and Niphates erecta were
      the most common in first location; Niphates erecta and Dysidea etheria in Playa
      Mero and Dysidea etheria, Niphates erecta and Amphimedon erina in Punta Brava.
      The species composition showed statistical differences between all three
      locations; Cayo Sombrero resulted the most diverse and even, followed by Playa
      Mero and Punta Brava. According to Sorensen Similarity Index results, Cayo
      Sombrero and Playa Mero were more similar, while Punta Brava resulted the most
      different. The variability in environmental conditions and the differential mass
      mortality effects of 1996 in all three reefs, were probably the main causes of
      the differences between their sponge communities. Nevertheless, we cannot
      conclude about the weight of these factors.

PMID- 24027921
TI  - [Spider diversity in cultures of Citrus sinensis (Rutaceae) in Corrientes
      province, Argentina].
AB  - Spiders are predators that reduce insect pest populations in agroecosystems. In
      spite that the presence of spider assemblages has been described in different
      crop plants, no reports have been done for Citrus species in Argentina. We
      studied the spider community associated with cultures of Citrus sinensis in the
      province of Corrientes, Argentina, in two plots (AM1 irrigated and AM2
      unirrigated) of 0.82 hectares each. Spiders were collected monthly by using
      pitfall traps, hand capture, agitation of foliage and sieving of soil litter. A
      total of 7174 specimens were collected (33 families, 44 genera and 200
      species/morphospecies). The AM1 recorded 3811 individuals (33 families, 179
      species/morphospecies) and AM2 3363 individuals (31 families, 174
      species/morphospecies). November, December and January showed the highest
      abundance in both plots. A total of 70% of collected spiders were juveniles.
      Eight families were the most abundant and represented 75% of spiders collected in
      both plots, the largest being Lycosidae. We identified eight guilds in both
      plots, for which the ground runners resulted the most abundant (AM1 n = 1341,
      s=39, n=999 AM2, s = 33), followed by orb weavers (AM1 n = 637, s = 36; AM2 n =
      552, s = 33), the stalkers (AM1 n = 471, s = 43, AM2 n = 453, s = 47) and the
      space web-builders (AM1 n = 446, s = 23; AM2 n = 342, s = 25). The analysis of
      alpha diversity in both plots (AM1H' = 4.161, J' = 0.802; AM2 H' = 4.184, J' =
      0.811) showed no significant differences (t = 1.083 p = 0.279). The linear
      dependences model was the one with the best fit results, where the species
      observed were more than estimated. Clench model estimated 90.9% of the spiders
      observed in the unit with irrigation and 90.6% in the unit without irrigation.

PMID- 24027922
TI  - Mandibular and postpharyngeal gland secretions of Acromyrmex landolti
      (Hymenoptera: Formicidae) as chemical cues for nestmate recognition.
AB  - Nestmate recognition is fundamental for the cohesiveness of the colony in social
      insects. Acromyrmex landolti is a higher Attini, a leaf-cutter ant with largest
      nest and morphological castes. We studied the location of the recognition signal
      of A. landolti on the whole ant body, the isolation effect on the capacity of
      nestmate recognition, and the role of the mandibular (MG) and post-pharyngeal
      glands (PPG) as putative sources for chemical recognition signals in this
      species. We performed behavioral bioassays and chemical analyses of MG and PPG
      glands; MG volatiles in different castes were also characterized. In order to
      determine the occurrence of nestmate recognition signals, behavioral tests were
      performed for which the whole body, body parts or gland extracts from a nestmate
      and an alien worker ant, were placed on the central axis of an active field
      trail. Besides, the isolation effect of the nestmate chemical signal persistence
      was evaluated by repeating the experiments with whole ant bodies after 12 h, 24 h
      and 48 h of isolation. The agonistic behavior of the ants on the trail was
      classified as inspection, threatening and biting. Gland volatiles were obtained
      by headspace solid phase microextraction, and PPG by solid sample analyses; and
      chemical analyses were performed using gas chromatography-mass spectrometry.
      Workers performed agonistic behaviors more frequently towards non-nestmate whole
      bodies, body parts and gland extracts, primarily those from the post-pharyngeal
      glands. Nestmate thoraces odorized with alien extracts were also recognized from
      aliens. Nestmate recognition ability persists for 12 h and 24 h after isolation,
      but decreases after 48 h, suggesting that the chemical signal changes over time.
      Inter-colonial chemical analyses showed no differences in the PPG hydrocarbon
      profiles, while the relative proportions of MG compounds showed significant
      differences between colonies. These results showed that nestmate recognition was
      achieved by MG volatiles. Possibly, the PPG secretion works as a matrix that
      absorbs MG volatiles. We report, for the first time, some mandibular gland
      compounds for the genus Acromyrmex and for the tribe Attini group.

PMID- 24027923
TI  - Synanthropy of sarcophagidae (Diptera) in La Pintada, Antioquia-Colombia.
AB  - Recently, populations of flies have increased in numbers given the elevated
      levels of organic matter waste produced by anthropic activities and domestication
      of animals. Such increase represents a worldwide health concern, since flies can
      be vectors of human diseases. The great variety of feeding and developmental
      habits of flies of the family Sarcophagidae taking place on animal corpses, feces
      and decomposed organic matter make them potential vectors of pathogens. Herein,
      we evaluated the synanthropic index (SI), as well as other ecological aspects of
      this family, through simultaneous monthly samplings in three areas with different
      degrees of human disturbance (urban, rural and forest). Each area had four van
      Someren Rydon traps, each one with a different bait (i.e., human feces, chicken
      viscera, fish and decomposing onion). Traps were active during 48 hours each
      month, and specimen collection was made every 12 hours. A total of 7 446
      Sarcophagidae individuals were collected (1275 males and 6171 females), belonging
      to 27 species and nine genera. Tricharaea (Sarcophagula) canuta (Sl = +96.67),
      Oxysarcodexia taitensis (SI = +93.85), Peckia (Peckia) chrysostoma (SI = +90.00)
      and Tricharaea (Sarcophagula) occidua (SI = +88.76) exhibited the highest values
      of synanthropy index, revealing a strong preference for human settlements. The
      most abundant species were Oxysarcodexia conclausa (21.80%), Ravinia effrenata
      (18.67%), Oxysarcodexia bakeri (11.45%) and Oxysarcodexia taitensis (10.20%), all
      of which exhibited preference for urban environments. Additionally, we are
      reporting seven new records of Sarcophagid flies for Colombia: Oxysarcodexia
      angrensis, Oxysarcodexia bakeri, Oxysarcodexia diana, Oxysarcodexia similata,
      Oxysarcodexia timida, Peckia (Peckia) pexata and Titanogrypa (Cucullomyia)
      placida.

PMID- 24027924
TI  - Trophic ecology of the exotic Lerma livebearer Poeciliopsis infans
      (Cyprinodontiformes: Poeciliidae) in the Lago de Patzcuaro, Central Mexico.
AB  - Exotic fish species has caused several impacts on aquatic biodiversity. The Lago
      de Patzcuaro has some well-studied exotic species, except the Lerma livebearer
      Poeciliopsis infans. This fish species was introduced into the Lago de Patzcuaro
      before 1997 and the aspects of its biology are still unknown. In this study we
      assessed aspects of the trophic ecology of this exotic fish, P infans, using gut
      content and stable isotope analysis to understand its capacity to tolerate
      anthropogenic environmental degradation in the Lago de Patzcuaro. We also
      determined its trophic guild position (TP) using the TrophLab Program and stable
      isotope. Niche breadth was calculated by standardized Levins' Index (Bi). Fish
      was captured with a seine during wet and dry seasons at six environmentally
      different sites and gut contents were obtained. We analyzed a total of 239 gut
      contents of P. infans. The contribution of each food item in the diet was
      quantified using frequency of occurrence and area percentage. The importance of
      each prey item was determined according to the index of relative importance
      (IRI), and the omnivory index (OI) was used to assess the feeding behavior. Fish
      were categorized by size and the diet was compared between fish sizes and sites.
      Dorsal muscle tissue and water hyacinth tissue was obtained for nitrogen isotope
      signature he fish can behave as a specialist (Bi = 0.39) or generalist (Bi =
      0.68) and as a primary consumer (TROPH = 2.2; TP = 2.3) with a feeding strategy
      that was the same at dif- f erent sizes, seasons and sites. None of the evaluated
      sites showed good environmental quality. We argue that P infans can tolerate
      changes in water quality and feeding items availability, because it can exploit
      resources in multiple trophic webs. However, this species could be dependent on
      habitat complexity, especially in the aquatic vegetation cover.

PMID- 24027925
TI  - [Micropterus salmoides (Pisces: Centrarchidae) reproduction in the Gustavo Diaz
      Ordaz reservoir, Sinaloa, Mexico].
AB  - Micropterus salmoides is an important fish species for sport fishing activities,
      condition that has promoted its introduction to different reservoirs in Mexico
      and worldwide. With the aim to improve its fisheries management, this research
      dealt with some reproductive aspects of this species in the Gustavo Diaz Ordaz
      reservoir, where it was studied from August 2008 through March 2011. To this end,
      we obtained 938 specimens, with gillnets of different sizes, to determine their
      total length (Lt, in cm), weight (Pt, in g), sex, gonadosomatic index, condition
      factor, fecundity and size at first maturity. Lt and Pt ranged from 15.9 to 63 cm
      (37.4 +/- 78.0) and 57 to 4431 g (731.7 +/- 619.0), respectively. The Pt-Lt
      relationship showed a positive allometric growth, with no significant difference
      between males and females (F = 0.9955, p = 0.3187). The male: female ratio
      obtained was 1:0.83. Mass spawning lasted from December to April. Size at first
      maturity was 33.7 cm and average fecundity was 32294 +/- 12878.7 oocytes/female.
      The gonadosomatic index was low from May through November, and increased between
      January and March. The condition factor was high before the spawning season and
      decreased after the reproductive period. We recommend a fishing ban from January
      to March, and to allow the capture size between 33 and 40 cm.

PMID- 24027926
TI  - Reproduction of Blackfin tuna Thunnus atlanticus (Perciformes: Scombridae) in
      Saint Peter and Saint Paul Archipelago, Equatorial Atlantic, Brazil.
AB  - The reproduction of Blackfin tuna Thunnus atlanticus has been described for
      coastal regions, and for a long time, this species was considered to be a
      strictly continental spawner. Recently, this species was observed around a
      seamount habitat 500 nautical miles Northeast of Brazil, located between South
      America and Africa. In this study we describe the reproductive biology of
      Blackfin tuna at Saint Peter and Saint Paul Archipelago (SPSPA). Male and female
      gonads were sampled from December 2008 to July 2010, and analyzed macro and
      microscopically. A total of 361 fish were sampled (247 males and 114 females).
      Males were more common than females, with a sex ratio of 2.2 male:1 female. The
      fork length (FL) of all sampled specimens ranged from 38 to 98cm, and larger
      length classes were more frequent in males. It was possible to distinguish six
      maturity phases for females: immature, developing, spawning capable, actively
      spawning, regressing and recovering. Five phases were identified for males:
      immature, developing, spawning capable, actively spawning and recovering. The
      gonad index (GI) mean monthly values ranged from 6.6 (SD = 4.1) to 58.4 (SD =
      34.7) for females, and from 2.6 (SD = 1.3) to 66.2 (SD = 30.4) for males. For
      both sexes, the largest GI values were observed at the beginning of the first
      semester of the year. Size at first maturity was estimated at 48cm FL and 55cm FL
      for females and males respectively. Approximately 80% of the specimens were
      adults and considered to be in reproductive conditions. Histological analysis of
      the ovaries and testes showed that most of the specimens were sexually mature and
      were reproductively active during all months of the year. However, females with
      mature ovaries, with large amounts of hydrated oocytes and post-ovulatory
      follicles, were mainly found from December to March, thus these months may
      constitute the main spawning season in SPSPA. Batch fecundity varied between
      272025 and 1,140584 oocytes for 56 and 68 cm FL females respectively. Oocyte
      development and spawning patterns suggest a multiple spawning behavior. The
      results revealed that Blackfin tuna is using the SPSPA as a spawning ground,
      similar to other species commonly observed in the same area during the same
      reproductive season.

PMID- 24027927
TI  - [Effect of environmental factors and fishing effort allocation on catch of the
      Spotted Eagle Ray Aetobatus narinari (Rajiformes: Myliobatidae) in Southern Gulf
      of Mexico].
AB  - Aetobatus narinari represents a fisheries target in Southern Gulf of Mexico, and
      it is currently considered a Near Threatened species by the IUCN red list. The
      information available of this batoid fish includes some biological and fishery
      aspects; nevertheless, little is known about the factors influencing on fishing
      operations and catches. In order to evaluate the effect of environmental factors
      and the fishing effort allocation by vessels on the target fishery of A. narinari
      in this area, a daily basis sampling was carried out on four small-scale vessels,
      from January to July 2009 (the entire fishing season), in two fishing localities
      (Campeche and Seybaplaya). A total of 896 rays were recorded from 280 fishing
      trips. A General Linear Model was used to predict the factors effect on the
      probability that fishing operations occurred, and on the probability for captures
      of at least one or three or five rays per vessel-trip. The probability that
      fishing operations occurred off Campeche was predicted by the lunar cycle, with
      the highest probability in the new moon period (66%) and a probability smaller
      than 35% for the other periods. The probability that fishing operations occurred
      off Seybaplaya was predicted by wind velocity, with higher probabilities at low
      wind velocity than at high wind velocity, and a 50% probability of fishing
      operations at 12-15 km/h. Catch rates off Seybaplaya were predicted by the
      vessel's factor (the effect of fishing effort allocation), the North wind season
      and sea surface temperature. The probability for captures of at least one and
      three rays per vessel-trip was predicted by the vessel's factor and the North
      wind season. One vessel had higher catch probability (83% for at least one ray
      and 43% for at least three rays) than the others (69 and 70% for at least one ray
      and 26% for at least three rays), and during the North wind season the catch
      probability was higher (96% for at least one ray and 72% for at least three rays)
      than out of that season (68% for at least one ray and 21% for at least three
      rays). The probability for capture at least five rays per vessel-trip was
      predicted by the sea surface temperature and the North wind season. At 23 degrees
      C the catch probability was of 49% and the probability gradually diminished to 4%
      at 28 degrees C, and during the North wind season the catch probability was
      higher (40%) than out of that season (7%). This study shows that some
      environmental factors and fishermen perceptions and experience (fishing effort
      allocation) influence on the catch rate of A. narinari, and that these factors
      must be considered in future studies on elasmobranch fisheries, mainly when
      comparisons between catch rates among seasons or regions are analyzed.

PMID- 24027928
TI  - Fish communities and trophic metrics as measures of ecological degradation: a
      case study in the tributaries of the river Ganga basin, India.
AB  - In India, freshwater aquatic resources are suffering from increasing human
      population, urbanization and shortage of all kind of natural resources like
      water. To mitigate this, all the major rivers have been planned for a river
      interlinking through an interlinking canal system under a huge scheme; yet, the
      baseline information on ecological conditions of those tropical rivers and their
      fish communities is lacking at present. In view of that, the present study was
      undertaken to assess the ecological condition by comparing the trophic metrics of
      the fish community, conservation status and water chemistry of the two tropical
      rivers of the Ganga basin, from October 2007 to November 2009. The analysis of
      trophic niches of the available fish species indicated dominancy of carnivorous
      (19 species) in river Ken and omnivorous (23 species) in Betwa. The trophic level
      score of carnivorous species was recorded similar (33.33%) in both rivers,
      whereas omnivorous species were mostly found in Betwa (36.51%) than Ken (28.07%).
      Relatively undisturbed sites of Betwa (B1, B2 and B3) and Ken (K2, K3 and K5)
      were characterized by diverse fish fauna and high richness of threatened species.
      The higher mean trophic level scores were recorded at B4 of Betwa and K4 of Ken.
      The Bray-Curtis index for trophic level identified the carnivorous species (>
      0.32) as an indicator species for pollution. Anthropogenic exposure, reflected in
      water quality as well as in fish community structure, was found higher especially
      in the lower stretches of both rivers. Our results suggest the importance of
      trophic metrics on fish community, for ecological conditions evaluation, which
      enables predictions on the effect of future morphodynamic changes (in the post
      interlinking phases), and provide a framework and reference condition to support
      restoration efforts of relatively altered fish habitats in tropical rivers of
      India.

PMID- 24027929
TI  - Three new species of Hemibrycon (Characiformes: Characidae) from the Magdalena
      River Basin, Colombia.
AB  - Fish biodiversity of aquatic ecosystems is highly threatened by different
      economic activities driven by human populations, and its description is
      increasingly a priority. For the Cauca-Magdalena River system we have described
      14 species, and the purpose of this paper was to describe three new species
      belonging to the same genus Hemibrycon from the Nare and Guatape River drainages
      of the middle Magdalena River, Colombia. The description was based on a series of
      200 specimens, and the use of morphometric, meristic and osteological characters,
      as well as fish distribution and morphogeometric analytical methods. We have
      found that Hemibrycon fasciatus n. sp. (n = 54) differs from other species of
      Hemibrycon (that also have a vertical humeral spot) in having: melanophores
      outlining the posterior margins of the scales along sides of body; humeral spot
      extending onto posterior margin of opercle; a dark lateral stripe, formed by deep
      pigment that is continuous with the peduncular spot; the toothed portion of the
      maxilla not reaching the dorsal margin of the dentary (vs. toothed portion of
      maxilla extending beyond dorsal margin of dentary); all maxillary teeth tricuspid
      (vs. some unicuspid teeth present on maxilla). H. cardalensis n. sp. (n = 64)
      differs in having: a vertically elongate humeral spot that extends one or two
      scales below the lateral line canal. H. cardalensis n. sp. differs from all
      congeners in having the pigment of the caudal spot restricted to the ventral half
      of the caudal peduncle, and in having melanophores around the anterior scales of
      the lateral line. Hemibrycon antioquiae n. sp. (n = 82) differs in having a
      circular humeral spot. It differs from the other species with a circular humeral
      spot, like H. mikrostiktos, in having a projection of disperse melanophores
      extending from the dorsal margin of the humeral spot to below the lateral stripe.
      Habitat data and environmental impacts caused by the construction of reservoirs
      for hydroelectric projects and other threats in the area are included, as well as
      a key to all species Hemibrycon present in the Magdalena River Basin. The
      synonymy of H. pautensis with H. polyodon is discussed and H. pautensis is
      revalidated.

PMID- 24027930
TI  - [Population demography in Rhinella arenarum (Anura: Bufonidae) and Physalaemus
      biligonigerus (Anura: Leiuperidae) in agroecosystems in the province of Cordoba,
      Argentina].
AB  - The advancing agricultural frontier has led to an important loss of natural
      habitats, with significant consequences for biodiversity. The demography for two
      species of anurans, Physalaemus biligonigerus and Rhinella arenarum, both
      associated with agricultural systems in the central region of the C6rdoba
      Province, were analyzed and compared in this study. Four sites were sampled:
      three agroecosystems with different alteration degrees (C1, C2 and SM1) and a
      fourth site not cultivated (SM2). The sampling was conducted during two
      reproductive periods, from September 2008 to April 2009 and September 2009 to
      April 2010. Individuals were captured using live pitfall traps for the
      metamorphic, juveniles and adults; and visual encounter survey, for the capture
      of eggs and larvae. With the abundance data, the survival for each age class was
      estimated using the KNM method (Kiritani Nakasuki Manly). With survival rates and
      fertility population, Leslie matrices were elaborated to obtain a quantitative
      projection of the population size. Altered environments showed lower eggs and
      larvae survival. Population projections were favorable in the site SM2 and were
      less favorable and a tendency to extinction, in sites dominated by crops. This
      study showed that the agroecosystems of this region are possibly inhospitable
      environments for reproduction and survival of the species studied. The aquatic
      stages in the life cycle of both species would be the more affected, since water
      bodies deterioration is present or may occur in those areas. We can recognize
      species-specific effects of agricultural ecosystems; P. biligonigerus was the
      most affected species, possibly because of their life histories and habitat
      requirements. We suggested that environmental degradation caused by the cropland
      in the central region of Argentina would impact on the demographics of the anuran
      populations in the area.

PMID- 24027931
TI  - Vocal patterns of adult females and juveniles Caiman yacare (Crocodilia:
      Alligatoridae) in Brazilian Pantanal wetland.
AB  - The Paraguayan caiman (Caiman yacare) is the main Caimaninae species occurring in
      the Brazilian Pantanal Wetland. Despite the relative availability of works
      focused on biology and conservation of the Paraguayan caiman, almost nothing is
      known about its vocal structure and behavior. We recorded aggressive calls of
      adult caiman females guarding nests and, afterwards, the distress calls of the
      new born juvenile caimans in seasonally flooded areas of the Nhecolandia
      (Southern Pantanal). The results of both observations and sonographic analyses
      diverged from studies with other crocodilian species. Aggressive vocalization of
      adult females of the Paraguayan caiman was longer and more complex than the same
      vocalization of larger Alligatoridae species. Vocalizations of the young caimans
      presented interspecific differences with other crocodilian offsprings. Moreover,
      we found statistically significant intraspecific variation in the distress call
      structure among different pods, even separated by few kilometers. Differences in
      distress call structure were tested by Canonical Discriminant Analysis (CDA). We
      obtained the squared Mahalanobis distances between the acoustic multivariate
      spaces of each pod provided by the CDA and compared with the geographic distance
      between the bays of origin of each pod through Mantel Test. The geographic
      distance by itself did not explain the differences found in the structure of the
      vocalization of young caimans from different pods. The adult females of
      Paraguayan caiman positively responded to playbacks of calls from juvenile
      caimans from pods of other regions, as well as to rough imitations of distress
      call. Since the adult caimans showed protective responses to quite heterogeneous
      vocalizations of distress by juveniles, we hypothesized that the variation in the
      distress call pattern may be associated to a low specificity in sound recognition
      by adult caimans.

PMID- 24027932
TI  - Successional stage, fragmentation and exposure to extraction influence the
      population structure of Euterpe precatoria (Arecaeae).
AB  - The neotropical palm Euterpeprecatoria is subject to extraction for its valuable
      palm heart. The development of management and conservation practices for this
      species requires understanding of its population structure, dynamics, and
      traditional use across the range of environments it inhabits, from different
      successional stages in continuous forest to forest fragments. Here, we analyzed
      how the population structure of E. precatoria varies with successional stage,
      fragmentation, and exposure to extraction, Since E. precatoria recruitment
      increases with disturbance, we expected seedling density to be higher in
      secondary forests and fragments relative to primary forests. The study was
      conducted from 2007-2008 in the Caribbean Slope of Costa Rica at Braulio Carrillo
      National Park (BCNP), La Selva Biological Station (LSBS), Manu Center, and Finca
      El Progreso (FEP). The first two sites had continuous primary and secondary
      forests (BCNP had one extracted primary forest); the last two consisted of
      primary forest fragments. Population structure was variable, with greater
      densities in the extracted primary forest, and in the secondary forests, as
      compared to primary forests and fragments. Palms < 5 m across all sites
      represented 50-90% of the total number of individuals. In sites that suffered
      historical over-extraction, local communities have lost the tradition of
      consuming this species. Understanding how population dynamics is affected by
      extraction and succession is essential to the design of sustainable management
      programs rooted in community participation.

PMID- 24027933
TI  - [Hurricane Paloma's effects on seagrasses along Jardines de la Reina Archipelago,
      Cuba].
AB  - Seagrasses are one of the most important coastal ecosystems since they promote
      organic matter flow, nutrient cycling, food availability and refuge. Until now,
      reports on damages caused by storms and hurricanes on seagrass beds are uncommon
      and highly variable. The seagrass meadows of the East end of Jardines de la Reina
      archipelago were surveyed from Nov. 29th to Dec. 5th of 2008, in order to
      determinate the effects from the passing of Hurricane Paloma: a category three
      storm on the Saffir-Simpsom scale. A rapid field assessment of the affected areas
      was carried out using the manta tow technique. In six sites, seagrass was
      quantitatively evaluated using a 15cm diameter core (four sampling units per
      site) and shoot density was calculated. Remote sensing techniques were used to
      estimate seagrass cover. To estimate the percentage of affected areas, a Region
      of Interest (ROI) was first created over a Landsat image. The percentage of
      seagrass affected within the ROI was estimated through direct georeferentiation
      of the contours of the damaged area and with a comparison to the total seagrass
      extension. To find possible explanations for damages, a false colour image was
      created using the near infrared band, to highlight the differences between
      emerged and submerged zones. The direction of winds was estimated using ArcGis
      9.2 creating circular buffers, from the centre of the hurricane and generating
      lines tangent to the buffers. Seagrass in the region was dominated by the
      angiosperm Thalassia testudinum. Regional mean density was 1 321 +/- 721
      shoots/m2, a value regarded as high for the Caribbean area. Seagrass meadows were
      partly affected by sediment accumulation on the shoots of T. testudinum and
      uprooting rhizomes. The 7.6 km2 disturbed area represented 1% of the total
      seagrass area. Other sites, closer to the centre of the hurricane, did not show
      any damages on the marine vegetation. The keys location with respect to the
      hurricane track was the most likely cause of the effects. To the North of the
      affected area there is an opening among the keys where the generation ofwaves,
      currents and turbulence could have occurred. Three years after the hurricane
      event, both vegetation cover loss and silt re-colonization by macroalgae species
      were observed within the affected area, by showing a patchily-vegetated
      landscape. This site is currently undergoing a temporal succession whose
      assessment demands a monitoring scheme, that will provide interesting information
      to document its future evolution and responsiveness against upcoming natural or
      anthropogenic events.

PMID- 24027934
TI  - Growth and photosynthetic performance of five tree seedlings species in response
      to natural light regimes from the Central Pacific of Costa Rica.
AB  - Environmental heterogeneity mostly dominated by differing light regimes affects
      the expression of phenotypic plasticity, which is important for plant growth and
      survival, especially in the forest understory. The knowledge about these
      responses to this heterogeneity is a key factor for forest restoration
      initiatives. In this study, we determine several phenotypic responses to
      contrasting light conditions in five native tree seedling species of La Cangreja
      National Park, Central Pacific of Costa Rica, four of them with threatened or
      relict populations. After 14 weeks at a medium gap condition (24% of full sun),
      seedlings were transferred and acclimated for 11 weeks to three different natural
      light regimes: large gap (LG), medium gap (MG) and small gap (SG), corresponding
      to 52%, 24%, 9% of the mean direct and indirect radiation at each site from full
      sun. Growth, biomass allocation and leaf gas exchange were measured after the
      acclimation period. Four species strongly reduced relative growth rate (RGR) in
      the lower light condition. Total biomass (TB) and RGR were different in Hymenaea
      courbaril and Platymiscium curiense. H. courbaril and Astronium graveolens had
      significant changes in the maximum assimilation rate, with a mean value in the LG
      of 11.02 and 7.70 micromolCO2/m2s, respectively. P. curuense showed the same
      trend and significant changes in RGR and biomass allocation. Aspidosperma
      myristicifolium and Plinia puriscalensis showed no adjustments to the light
      regimes in any of the measured variables. This study remarks the importance of
      determining the growth and physiological performance of these tree native
      species. It also demonstrates that the most threatened species are those with the
      less plastic responses to the light regimes, which stresses the difficult
      situation of their natural populations. This study highlights an urgent
      definition of the conservation and restoration needs of the degraded forests of
      the Costa Rican Central Pacific area, where these species dwell.

PMID- 24027935
TI  - [Natural regeneration response in mangroves of the gulf of Uraba (Colombia) to
      the environmental and intra-annual climate variability].
AB  - The natural regeneration process allows the mangrove forests remain over time.
      Both, biological and physical factors can affect the establishment and early
      stages along the development of trees. This study examined the response of
      natural regeneration of mangroves in the Turbo River delta and El Uno bay (Uraba
      Gulf, Colombia) to intra-annual environmental variability. We quantified
      mortality, survival and recruitment of seedlings of three mangrove species,
      seasonally during one year, in 72 semi-permanent sub-plots of 1 m2. In the sub
      plots, the total height and the diameter at the base of the stem of all mangrove
      seedlings with basal diameter less than 2.5cm were measured. Damage by herbivores
      was also recorded to each seedling. While Laguncularia racemosa recorded the
      highest rates of mortality, Rhizophora mangle showed the highest survival rate
      during the study period, although Avicennia germinans dominated the natural
      regeneration. Through a Redundancy Analysis these processes were associated to
      environmental variables such as: Direct Site Factor-DSF (sunlight), sediments
      input rate, herbivory, distances from mangroves to the river, to inner lakes, and
      to the coastline. These variables explained 43% of the natural regeneration
      variation; sedimentation rate was the most important variable, while light was
      very representative for the R. mangle survival. Based on historical records of
      precipitation, Turbo River flow rate and associated sediment loads, it was
      established that during the highest precipitation peak, the survival of all
      species decreases and during the dry season, when the conditions of flooding and
      sediments input were lower, it was improved. The results indicated that the
      sediments input rates and sunlight play an important role in the survival of
      natural regeneration of evaluated mangrove species.

PMID- 24027936
TI  - Toxicological effects of prolonged and intense use of mosquito coil emission in
      rats and its implications on malaria control.
AB  - Mosquito coil is a vector control option used to prevent malaria in low income
      counties, while some studies have addressed this issue, additional reseach is
      required to increase knowledge on the adverse health effects caused by the
      prolonged use of coils. In this study we investigated the toxicological effects
      of fumes from two locally manufactured mosquito coil insecticides (with
      pyrethroids: transfluthrin and d-allethrin as active ingredients) on male albino
      rats. For this, we recorded the haematological and biochemical indices, and made
      histopathology and mutagenicity evaluations in rats exposed to mosquito fumes
      during 2, 4, 8, 12 and 16 week periods. Haematological determination was
      performed using automated hematology analyzer to determine White Blood Cell
      (WBC), Packed Cell Volume (PCV), Red Blood Cell (RBC) and Platelet (PLT) counts,
      while biochemical evaluations were determined using available commercial kits.
      Gross histopathological changes were studied for the kidney, liver and lungs in
      sacrificed rats. The rat sperm head abnormalities assessment was used to evaluate
      mutagenicity. Mosquito coil fumes produced significant increase (P < 0.05) in the
      levels of total protein, total albumin and bilirubin, when animals were exposed
      from two weeks to 16 weeks with transfluthrin. Similarly, elevation in the
      activities of aspartate amino transferase, alanine amino transferase and alanine
      phosphatase, increased significantly in both insecticides. Increase in WBC, RBC
      and PCV were recorded for all the exposure periods, however PLT count showed no
      significant increase (P > 0.05). Mutagenicity assessment revealed sperm
      abnormality was statistically significant (P < 0.05) compared with the control at
      8, 12 and 16 weeks post exposure to transfluthrin. Histological studies revealed
      severe lung damage evidenced by interstitial accumulations, pulmonary oedema and
      emphysema in exposed rats. Intracellular accumulations and severe sinusoidal
      congestion of liver cells were observed from 12 weeks exposure, indicating liver
      damage. Our studies indicate that mosquito coil fumes do initiate gradual damage
      to the host. These pathological effects must be taken into consideration by the
      malaria control program, particularly when regulating their long term and indoor
      usage.

PMID- 24027937
TI  - [Necrophilous beetles diversity (Coleoptera: Scarabaeidae, Silphidae,
      Staphylinidae and Trogidae) in a semiarid area of Zapotitlan de las Salinas
      Valley, Puebla, Mexico].
AB  - Mexico is constituted of arid and semiarid areas in more than half of its land
      extension, where most of their resources are available only during the rainy
      season. For those species that recycle resources, such as the carrion fauna, this
      represents a highly active season; however, the biological and diversity patterns
      of carrion fauna are poorly understood in these areas. Here, we studied the
      abundance, diversity and richness of the Scarabaeidae, Silphidae, Staphylinidae
      and Trogidae families in the Zapotitlan de las Salinas Valley in Puebla, Mexico.
      Over a one-year period, monthly samples were collected from five different
      vegetation systems that included the scrublands, a columnar cactus landscape, and
      altered vegetation. Samples were collected with the use of NTP-80 traps baited
      with squid, and data on abundance and richness were obtained and evaluated, with
      respect to monthly precipitation and sampling site location. We collected a total
      of 613 insects from 12 genera and 15 species. Across systems, Staphylinidae
      showed the greatest richness (nine species) and abundance (74.2%), followed by
      Scarabaeidae (21.9%), Silphidae (2.9%) and Trogidae (1%). Significant differences
      were observed between sites and months; nevertheless, no relationship was
      observed between abundance and temperature or precipitation. Across taxonomic
      groups, abundance and richness were most evident for scrub sites, while a greater
      abundance during the dry season was obtained. The results of this study indicated
      that the carrion faunal community composition is closely related to the type of
      vegetation and did not depend on the rainy season. In spite that lesser carrion
      fauna was observed in this area when compared to other regions of Mexico, this
      report constitutes a significant contribution to our understanding of the
      ecological role of this fauna in arid areas.

PMID- 24027938
TI  - Photosynthesis of seedlings of Otoba novogranatensis (Myristicaceae) and Ruagea
      glabra (Meliaceae) in abandoned pasture, secondary forest and plantation habitats
      in Costa Rica.
AB  - Enrichment planting in naturally recovering secondary forests or in tree
      plantations is increasingly being used as strategy to restore later-successional,
      large-seeded tropical forest trees. We seeded two tree species (Otoba
      novogranatensis and Ruagea glabra) in three agricultural sites in Southern Costa
      Rica: abandoned pastures, eight to ten year old secondary forests and three year
      old tree plantations (containing two N-fixing of four total tree species). We
      measured micrometeorological conditions, soil water content, plant water
      potential, leaf area, foliar C and N, and photosynthesis to better understand
      mechanistic responses of seedlings to conditions in the different successional
      habitats. Micrometeorological conditions, soil water content, and plant water
      potential were generally similar across habitats. Certain aspects of leaves (such
      as Specific Leaf Area and foliar N content), and photosynthesis (e.g. quantum
      yield and electron transport rate) were highest in the plantations, intermediate
      in the secondary forests, and lowest in abandoned pastures. Enhanced rates of
      photosynthetic biochemistry (such as Vxmax and Jmax) and Photosystem II
      efficiency (e.g. thermal energy dissipation) occurred in leaves from the
      plantations compared to the abandoned pastures, which may be related to higher
      leaf %N content. Results suggest that foliar N may be of greater importance than
      soil water content and micrometeorological factors in driving differences in
      photosynthetic processes across planting habitats. Planting seeds of these two
      species in plantations containing three year old trees (including two N-fixing
      species) enhances certain aspects of their photosynthesis and growth, compared to
      seedlings in abandoned pastures with non-native grasses, and thus can help
      increase forest recovery on abandoned agricultural lands.

PMID- 24027939
TI  - [Altitudinal richness patterns of Papilionidae, Pieridae and Nymphalidae
      (Lepidoptera) in Mexican mountain areas].
AB  - Altitudinal richness patterns of Papilionidae, Pieridae and Nymphalidae
      (Lepidoptera) in Mexican mountain areas. Butterflies constitute an useful group
      to investigate biodiversity patterns in specific geographic areas. The aim of
      this study was to describe the altitudinal patterns distribution and to recognize
      the main grouping factors of these families. We conducted a comparative study
      between the butterfly fauna (Papilionidae, Pieridae and Nymphalidae) of five
      Mexican mountain ranges (Sierra de Manantlan, Sierra de Atoyac de Alvarez,
      Loxicha Region, Teocelo-Xalapa and Sierra de Juarez), that included 34 sites of
      altitudinal ranges from 100 to 2 820m. Data was obtained from the Zoology Museum
      of the National University of Mexico, and comprised more than 60 000 butterfly
      records of 398 taxa (subspecies level) proceeding during the last 35 years. Fauna
      similarity between localities were analyzed using a cluster analysis by Sorensen
      similarity coefficient. Species richness showed a general tendency to decrease
      with altitude; the main difference was found between the locality with higher
      altitude and the rest of the sites. The principal factors affecting the
      identified clusters followed this order: the location in Pacific or Atlantic
      slope, and location on a particular mountain range. Three altitudinal levels (low
      elevations, up to 1 200m; intermediate elevations, from 1200 to 1800 m; and high
      elevations, from 1800 to 2500 m) were described in accordance to their main
      characteristic taxa. While Neartic elements were common in the highest
      altitudinal floor, Neotropical taxa were common in the lowest one. It was more
      difficult to characterize the intermediate level in which a high number of
      localities were clustered; this intermediate level was characterized by the
      presence of some endemic species. The results suggest that historical factors are
      preeminent in butterfly fauna composition in these areas. Future studies may
      include other Mexican mountain areas to obtain more information on the different
      factors (latitude, altitude, slope) influencing biodiversity patterns.

PMID- 24027940
TI  - Spatial distribution of Guaiacum sanctum (Zygophyllaceae) seedlings and saplings
      relative to canopy cover in Palo Verde National Park, Costa Rica.
AB  - The spatial distribution of individuals is a fundamental property of most species
      and constitutes essential information for the development of restoration and
      conservation strategies, especially for endangered plant species. In this paper
      we describe the spatial distribution of different size classes of the endangered
      tropical tree Guaiacum sanctum and the effect of canopy cover on spatial
      aggregation. Adult G. sanctum were located and mapped in a 50 ha plot in Palo
      Verde National Park, Costa Rica. Seedlings, saplings and juveniles were mapped to
      the nearest centimetre and permanently marked in three 50 x 50 m subplots. Within
      each subplot spatial aggregation was assessed using Ripley's K statistic and
      canopy opening readings were performed every 5 m using a densitometer. Kriging
      spatial interpolation and Monte Carlo simulations were used to determine if
      average canopy cover differed among size classes. Individuals of G. sanctum were
      spatially aggregated at all size classes with seedlings being the most frequent
      size class in all subplots. Seedlings were found predominantly in areas with
      significantly higher canopy cover. In contrast, juveniles were more likely found
      in areas with higher light availability. The high number of seedlings, saplings,
      and juveniles relative to adults suggests that populations of G. sanctum in PVNP
      are expanding. Light availability and canopy structure are important factors
      shaping the spatial distribution of this species. The contemporary demographic
      structure of G. sanctum is dependent on forest gap dynamics and changes in human
      disturbance during the past 25 years.

PMID- 24027941
TI  - Cultural similarities and differences in the perception of emotional valence and
      intensity: a comparison of Americans and Hong Kong Chinese.
AB  - Despite being challenged for their ecological validity, studies of emotion
      perception have often relied on static, posed expressions. One of the key reasons
      is that dynamic, spontaneous expressions are difficult to control because of the
      existence of display rules and frequent co-occurrence of non-emotion related
      facial movements. The present study investigated cross-cultural patterns in the
      perception of emotion using an expressive regulation paradigm for generating
      facial expressions. The paradigm largely balances out the competing concerns for
      ecological and internal validity. Americans and Hong Kong Chinese (expressors)
      were presented with positively and negatively valenced pictures and were asked to
      enhance, suppress, or naturally display their facial expressions according to
      their subjective emotions. Videos of naturalistic and dynamic expressions of
      emotions were rated by Americans and Hong Kong Chinese (judges) for valence and
      intensity. The 2 cultures agreed on the valence and relative intensity of emotion
      expressions, but cultural differences were observed in absolute intensity
      ratings. The differences varied between positive and negative expressions. With
      positive expressions, ratings were higher when there was a cultural match between
      the expressor and the judge and when the expression was enhanced by the
      expressor. With negative expressions, Chinese judges gave higher ratings than
      their American counterparts for Chinese expressions under all 3 expressive
      conditions, and the discrepancy increased with expression intensity; no cultural
      differences were observed when American expressions were judged. The results were
      discussed with respect to the "decoding rules" and "same-culture advantage"
      approaches of emotion perception and a negativity bias in the Chinese collective
      culture.

PMID- 24027942
TI  - Stealing is not gross: language distinguishes visceral disgust from moral
      violations.
AB  - The similarity between moral and visceral disgust is a current topic of debate.
      One method of investigating this issue has been to examine the use of language.
      Prior work has shown that the words disgust and anger are often used
      interchangeably to describe offense toward immoral behavior involving harm
      (autonomy violations), whereas "grossed out" is reserved for viscerally repulsive
      stimuli. Based on these findings we developed a questionnaire and tested 126
      undergraduates for how they used the words disgusted, angry, grossed out, and
      morally right or morally wrong to rate various responses toward ethics of
      autonomy social situations. We found that grossed out was least endorsed for
      these transgressions and that ratings on this measure did not correspond to
      ratings of moral wrongness. Moreover, individual differences in visceral disgust
      sensitivity had no association with participants' evaluations or use of any of
      the descriptors. By contrast, ratings for angry and disgusted were equivalently
      and highly endorsed for autonomy violations, and the ratings given with these
      descriptors also corresponded to the ratings given for moral wrongness. These
      findings add to growing evidence that moral disgust is not visceral (gross) but
      rather appears to be representative of anger even though autonomy violations are
      often labeled as "disgusting".

PMID- 24027943
TI  - Bullets versus burgers: is it threat or relevance that captures attention?
AB  - Previous studies have found that potentially dangerous stimuli are better at
      capturing attention than neutral stimuli, a finding sometimes called the threat
      superiority effect. However, non-threatening stimuli also capture attention in
      many studies of visual attention. In Experiment 1, the relevance superiority
      effect was tested with a visual search task comparing detection times for
      threatening stimuli (guns), pleasant but motivationally relevant stimuli (food),
      and neutral stimuli (flowers and chairs). Gun targets were detected more rapidly
      than both types of neutral targets, whereas food targets were detected more
      quickly than the neutral chair targets only. Guns were detected more rapidly than
      food. In Experiment 2, threatening targets (guns and snakes), pleasant but
      motivationally relevant targets (money and food), and neutral targets (trees and
      couches) were all presented with the same neutral distractors (cactus and pots)
      in order to control for the valence of the distractor stimulus across the three
      categories of target stimuli. Threatening and pleasant target categories
      facilitated attention relative to neutral targets. The results support the view
      that both threatening and pleasant pictures can be detected more rapidly than
      neutral targets.

PMID- 24027944
TI  - The gestural misinformation effect: skewing eyewitness testimony through gesture.
AB  - The susceptibility of eyewitnesses to verbal suggestion has been well documented,
      although little attention has been paid to the role of nonverbal communication in
      misinformation. Three experiments are reported; in each, participants watched
      footage of a crime scene before being questioned about what they had observed. In
      Experiments 1 and 2, an on-screen interviewer accompanied identically worded
      questions with gestures that either conveyed accurate information about the scene
      or conveyed false, misleading information. The misleading gestures significantly
      influenced recall, and participants' responses were consistent with the gestured
      information. In Experiment 3, a live interview was conducted, and the gestural
      misinformation effect was found to be robust; participants were influenced by
      misleading gestures performed by the interviewer during questioning. These
      findings provide compelling evidence for the gestural misinformation effect,
      whereby subtle hand gestures can implant information and distort the testimony of
      eyewitnesses. The practical and legal implications of these findings are
      discussed.

PMID- 24027945
TI  - The effects of repeated thought suppression attempts on thought occurrence.
AB  - In the thought suppression literature the completion of one suppression and one
      expression phase is called an indulgence cycle. The current study aimed to
      determine the effects on thought frequency of entering multiple indulgence
      cycles. Participants were assigned to one of two groups. The repeated suppression
      group was required to complete 3 suppression and 3 think free phases in
      alternating fashion. The suppress think free group was required to complete 1
      suppression phase before entering 5 think free phases. Participants pressed a
      spacebar to report each unwanted target thought occurrence. Participants in the
      repeated suppression group experienced maintenance of the number of unwanted
      thought intrusions in both suppression and think free phases, whereas those in
      the suppress think free group experienced a significant decline in target thought
      occurrence. The maintenance effect of engaging in repeated suppression attempts
      is discussed.

PMID- 24027946
TI  - Novel word processing.
AB  - People who text messages often shorten words by eliminating internal letters
      (e.g., "climate, clmte"). Although these novel representations (i.e., subset word
      forms) are not true words, sentence context may prime semantic activation. We
      hypothesized that if participants are presented with a context sentence prime
      containing a subset form target word, then participants' performance should
      improve when the stimulus is presented to the left visual field/right hemisphere
      (LVF/RH) because the RH is less reliant on correct orthography than the left
      hemisphere (LH). We also hypothesized that participants' bias of processing novel
      stimuli is a function of visual field and hemisphere presentation. The results
      supported the hypothesis. When participants were shown subset word forms in the
      LVF/RH, their accuracy was significantly greater than when they were shown in the
      RVF/LH. Additionally, signal detection theory was applied to the results and
      substantiated the findings that participants' bias toward processing subset and
      orthographically correct words is a function of visual field and hemisphere
      presentation.

PMID- 24027947
TI  - A disconfirming strategy is not necessarily better than a confirming strategy.
AB  - College students were presented with 4 events to be explained. Each event was
      accompanied by either a target explanation or a target and an alternative, and
      all explanations were causal mechanistic. For each event, participants were also
      presented with 12 pieces of information. Four of the 12 pieces were causally
      consistent with the target, 4 with the alternative, and 4 were neutral.
      Participants were assigned to one of 3 strategy conditions, depending on what
      they were explicitly told to do: confirm, disconfirm, or evaluate the target
      explanation. People told to disconfirm were more likely than people in the other
      conditions to cite, as strategy appropriate, information that was in fact
      neutral. In addition, across strategy conditions, the presence of an alternative
      decreased the likelihood of identifying, as appropriate to the strategy,
      information that was strategy inappropriate. Results are discussed in terms of
      inference to the best explanation and in terms of confirmation bias.

PMID- 24027948
TI  - Nostalgia: retreat or support in difficult times?
AB  - The relationship between nostalgia and coping during difficult times was explored
      in 2 empirical studies. In the first, 80 undergraduates, 60 women and 20 men,
      completed the Nostalgia Inventory, a measure of nostalgia proneness, the COPE
      Inventory, a dispositional measure of strategies for coping with stressful
      events, and the Childhood Survey, a survey of impressions of childhood
      experiences. Nostalgia proneness correlated with use of adaptive coping,
      including emotional social support, expressing emotions, turning to religion, and
      suppressing competing activities, and did not correlate with escapist or
      avoidance strategies, including denial, behavioral disengagement, and substance
      abuse. Nostalgia proneness was related positively to favorable emotional and
      behavioral childhood experiences and did not correlate with adverse experiences.
      Favorable impressions of childhood correlated positively with adaptive coping
      strategies and inversely with dysfunctional ones, whereas unfavorable childhood
      experiences correlated positively with dysfunctional coping. Regression analyses
      suggested that the relationship between nostalgia proneness and certain coping
      strategies may be mediated in part by childhood experiences. In a second study,
      100 undergraduates, 86 women and 14 men, completed the Nostalgia Inventory,
      recalled autobiographical memories that illustrated how childhood is either
      special or similar to their present life, and rated their likely use of
      strategies in dealing with 2 hypothetical problems. Nostalgia proneness
      correlated with emotional and instrumental social coping and with the goal
      directed strategies of planning, taking action, and positive reframing. Further
      research is recommended to explore the role of childhood memories in coping and
      to identify mechanisms that mediate the relationship between nostalgia and
      coping.

PMID- 24027949
TI  - Food for thought.

PMID- 24027950
TI  - Relationship between knowledge, attitudes, and self-efficacy of nurses in the
      management of pediatric pain.
AB  - Pain management is a very important aspect of nursing care of the pediatric
      patient. A nurse's knowledge and attitude can affect his or her ability to
      adequately provide pediatric pain management. This study examined the level of
      knowledge of pediatric pain management, the attitudes of nurses, and the level of
      self-efficacy of pediatric nurses in acute care. In addition, the relationship
      between the years of experience and the levels of knowledge, attitudes, and self
      efficacy were examined. A cross-sectional, correlational design was used in a
      convenience, non-probability sample of 25 pediatric nurses. Nurses volunteering
      to participate in the study were asked to complete two instruments: Pediatric
      Nurses' Knowledge and Attitudes Survey Regarding Pain (PNKAS-Shriners Revision)
      (Manworren, 2000, 2001) and Nurses' Self-Efficacy in Managing Children's Pain
      (Chiang, Chen, & Huang, 2006). There was no statistically significant
      relationship between knowledge and self-efficacy (r = 0.039, p = 0.853) or
      knowledge and years of nursing experience (r = 0.050, p = 0.822). There was a
      statistically significant relationship between the level of knowledge and the
      years of pediatric experience (r = 0.404, p = 0.05) and knowledge and the
      membership in a professional nursing organization (t = 4.050, p = 0.004). Years
      of pediatric nursing experience correlated with significantly higher knowledge
      levels, as did a membership in a professional nursing organization. Further,
      education may benefit pediatric nurses in regard to their management of pediatric
      pain. Research is needed to examine the effects of self-efficacy on pediatric
      pain management and how it relates to the level of knowledge.

PMID- 24027951
TI  - Children 'draw-and-tell' their knowledge of genetics.
AB  - The purpose of this study was to explore children's early understanding of basic
      genetic/genomic concepts using an innovative, child-sensitive approach to data
      collection. Exploratory, qualitative study using art-based "Draw-and-Tell
      Conversation" interviews with children were used. Each conversational interview
      was guided by two drawing completion tasks and a semi-structured interview guide.
      Data were analyzed using qualitative content analysis. In this study, 27 children
      7 to 10 years of age shared their understanding of basic genetic/genomic concepts
      in their drawings and conversations. Data were organized into four categories: 1)
      Inside the Body, 2) Under the Microscope, 3) It's Genetic, and 4) In Our World.
      Using a child-sensitive approach to data collection, children revealed a range of
      understanding about basic genetic concepts, including DNA, disease causation,
      risk, and inheritance. Data suggest informal family conversations and media
      exposure inform children's early understanding, highlighting the need to be aware
      of the sources and content of information available to children. Nurses play a
      central role in assessing children's genetic/genomic knowledge. The Draw-and-Tell
      Conversation is a novel approach that can be used to support parents as they
      approach and discuss genetic concepts with their children.

PMID- 24027953
TI  - Presence of type 2 diabetes risk factors in children.
AB  - This study aimed to identify the prevalence of type 2 diabetes risk factors among
      elementary school-age children and determine eligibility for type 2 diabetes
      screening. A cross-sectional review of 971 school-based health clinic medical
      records of children in grades 1 through 5 was conducted. Relationships of risk
      factors associated with type 2 diabetes mellitus were examined to determine the
      prevalence of these risk factors in elementary school-age children. Screening
      guidelines for type 2 diabetes were applied to determine the prevalence of
      students meeting criteria for further screening. Almost 40% of the students had a
      body mass index (BMI) above the 85th percentile for age and gender. Forty-nine
      percent of the students belonged to a high-risk ethnic group. Acanthosis
      nigricans, an indicator of insulin resistance, was identified in nearly 27% of
      the student records. Forty-eight percent of the records identified the student as
      having a family history of diabetes. Significant correlations were found between
      the presence of acanthosis nigricans, high BMI, and a family history of diabetes.
      According to screening guidelines for type 2 diabetes in children, 39.3% of the
      elementary school children 10 years of age and older were eligible for type 2
      diabetes screening. Almost 40% of children younger than 10 years of age had risk
      factors associated with screening criteria. These findings support the need for
      early detection of high-risk children and intervention strategies to decrease
      modifiable risk factors in elementary school-age children. The school nurse is in
      a pivotal role of identifying such at-risk students during annual, routine health
      screening practices.

PMID- 24027952
TI  - Adolescents' perspectives of parental practices influence diabetic adherence and
      quality of life.
AB  - This study investigated whether perceived parental support and different
      parenting styles were related to adherence to diabetes management, metabolic
      control, and perceived quality of life of adolescents diagnosed with type 1
      diabetes. Adolescents between 12 and 18 years of age (N = 102) diagnosed with
      type 1 diabetes for at least one year participated. Parents were classified into
      one of four groups (authoritative, authoritarian, permissive, or neglectful)
      based on their adolescents' surveyed perceptions of their general support and
      their overall responsiveness and demandingness. Perceived parental support was
      significantly correlated with adherence. Adolescents who perceived their parents
      to have authoritative parenting styles also had better adherence to their
      prescribed treatment plan as well as better perceived quality of life.
      Adolescents experience better management outcomes when adolescents and parents
      become interdependent by working together to achieve these outcomes.

PMID- 24027954
TI  - Health risks associated with late-preterm infants: implications for newborn
      primary care.
AB  - This integrative literature review focuses on the health risks associated with
      late-preterm infants (34 to 36 and 6/7 weeks gestation) and the implications for
      newborn primary care providers and pediatric nurses. Common morbidities in the
      late-term population included hyperbilirubinemia, respiratory compromise,
      hyperglycemia and poor feeding, temperature instability, and infection. Primary
      care providers should be aware of these morbidities to be sure risk-focused
      evaluation is performed during and after the birth hospitalization, and treatment
      is administered when necessary.

PMID- 24027955
TI  - Making meaning when a child has mental illness: four mothers share their
      experiences.
AB  - Approximately 15 million children in the United States can currently be diagnosed
      with a mental health disorder (APA, 2013). Families of these children experience
      not only grief and the challenge of managing the disorder, but also stigma,
      including rejection, misunderstanding, and a feeling of isolation. Nonetheless,
      some parents find or develop approaches for "making meaning" from the experience.
      Interviews of four mothers of children with mental illness demonstrate "making
      meaning" in ways that provide for personal growth, fulfillment, and support,
      while engaging in efforts that ease the journey for others in similar
      circumstances.

PMID- 24027956
TI  - The critical need for black nurses.

PMID- 24027957
TI  - Interprofessional education: an IOM imperative.

PMID- 24027958
TI  - Effects of social support and spirituality on weight loss for rural African
      American women.
AB  - Obesity continues to be an increasing health problem among African-American
      women. A 10-week weight-loss intervention program designed to address the problem
      in these women. Two different interventions (spiritually based and nonspiritually
      based) were tested, and both utilized a pre-test, posttest design On the basis of
      theories of social support, it was expected that participation in the
      intervention would produce a significant reduction in weight. In addition, the
      spiritual-based weight-loss program was hypothesized to produce greater weight
      reduction than the standard health (non-spiritual) program. The results
      demonstrated that the average weight and BMI of all participants in either a
      spiritually-based or a nonspiritually-based program were lower at the completion
      of the intervention program. In addition, the average weight and BMI loss for the
      spiritual group was significantly greater than the average weight and BMI loss
      for the non-spiritual group.

PMID- 24027959
TI  - No Child Left Behind and the teaching of character education.
AB  - The purpose of this qualitative study was to determine the perceptions of
      administrators and educators and to ascertain if the No Child Left behind
      Legislation is having a negative impact on students in terms of character
      building and moral development. Middle school administrators and educators from
      public and Catholic schools completed a 17 item questionnaire and interviews to
      obtain the views of the legislation. The questionnaire was a 4 point likert scale
      with the opportunity for comments. A total of seventy-six teachers and
      administrators involved in the study. They were given the survey to complete and
      asked if they would consider a face to face interview. A total of 162 educators
      invited to participate 76 responded expressing the need for the legislation
      however they noted that the changing of the curriculum has posed a real challenge
      in terms developing character and moral development.

PMID- 24027960
TI  - A journey to the bible lands: a call from the past to the present in astonishing
      ways.
AB  - I traveled to the Middle East six times between 1978 and 200. These trips will
      always remain among my most precious memories. These trips included visiting Tele
      Aviv, Jerusalem (Old and New), Bethlehem, Haifa, Galilee, Golan Heights,
      Tiberius, Temple Mount, Ein Gedi Beach (Dead Sea), the Masada, Sinai, Caesarea,
      and Megiddo (Armageddon). The Church of Our Lord Jesus Christ, Inc. (New York
      City) was the Host Church, with Dr. Robert Spellman (a Senior Professor at Essex
      County College (New Jersey), Bishop/Pastor of the Macedonia Church of Our Lord
      Jesus Christ (Newark, NJ), and Bible Seminar Teacher, was the Tour Leader. During
      these travels, many airlines were used, including British Airways, El Al,
      Olympia, Lufthansa, and Alitalia. Side trips included Egypt, Jordan (Petra), and
      Europe (Greece, London, Paris, Rome). This tour in my own words, hopefully will
      entice and enlighten others to plan a trip to the most sacred ground on earth. I
      trust there will be as much enjoyment as I have had and am still having in
      sharing the biblical knowledge as it relates to the Bible lessons I learned over
      the years in Sunday School and actually comparing them today with the Holy Land
      itself.

PMID- 24027961
TI  - [The use of iontophoresis in corneal crosslinking technique].
AB  - Iontophoresis is a method of facilitating the penetration of a drug through an
      intact tissue in the presence of an low intensity electrical current. In corneal
      crosslinking technique, iontophoresis is used for transepitelial impregnation of
      cornea with riboflavin. Compared to passive technique of corneal impregnation,
      iontophoresis shortens the time needed for impregnation, the time of exposure to
      UVA radiation and does not require de-epithelialisation.

PMID- 24027962
TI  - [Enophthalmos in an orbital tumor].
AB  - Enophtalmus is an unusual sign of the orbital tumors often represented by
      proptosis. One patient with enophtalmus and intraorbital tumor and aplasy is
      presented. The treatment of choice of orbital tumor is complete surgical excision
      and careful follow-up. Considering the more aggressive course followed by
      recurrent tumor, correct diagnosis and management is essential.

PMID- 24027963
TI  - [Bilateral blindness in endogenous endophthalmitis with fulminant course -- a
      clinical case].
AB  - We present the case of man with endogenous endophtalmitis AO, with Insulin
      dependent Diabetes Mellitus type 2 and Viral hepatitis type C. The prognosis was
      reserved in the context of the underlying disease, with loss of his visual acuity
      OD and evisceration OS. Despite the correct treatment and many clinical,
      laboratory, imaging and interclinical examinations, etiologic diagnosis was
      established with great difficulty and very late.

PMID- 24027964
TI  - [Central retinal vein occlusion associated with severe bilateral carotid
      stenosis].

PMID- 24027965
TI  - [The effect of crystalline lens extraction on intraocular pressure in patients
      with primary open-angle glaucoma].
AB  - This issue presents the results of a study on patients with cataract and primary
      open angle glaucoma who suffered lens extraction for cataract. We analise the
      effects of the lens extraction on the level of intraocular pressure at this
      patients.

PMID- 24027966
TI  - [Assessment of central corneal thickness in children with diabetus mellitus type
      I].
AB  - PURPOSE: To evaluate the correlations between central corneal thickness and type
      1 diabetes in children. METHODS: Central corneal thickness was measured for one
      hundred children with type 1 diabetes mellitus (study group) and one hundred
      healthy children (control group), using TOPCON TRK-1P
      autorefractokeratotonometer. RESULTS: The average central corneal thickness in
      diabetic children was 541.13 +/- 30,985 microns for the right eye and 538.28 +/-
      32, 773 microns for the left eye; in control group--528.11 +/- 33,565 microns for
      the right eye and 526.89 +/- 30,483 microns for the left eye. CONCLUSIONS:
      Diabetic children have a significantly increased central corneal thickness when
      compared with non-diabetic children.

PMID- 24027967
TI  - [Different significance in normal subjects and in glaucoma patients tested with
      Optopol PTS-910, in the galucoma program].
AB  - PURPOSE: to quantify the inter-test variability (dB) for the Optopol PTS
      automated perimeter, Glaucoma Fast threshold program. MATERIALS AND METHOD: A
      prospective study was performed on 166 glaucomatous patients and a control group
      of 30 normal subjects, tested by complete ophthalmological exam and automated
      perimetry (Optopol PTS-910). The visual field was tested weekly for 4 consecutive
      weeks. The visual field defects were classified according to the Aulhorn-Karmeyer
      descriptive scale. RESULTS: For the control group, the medium inter-test
      variability was of 1.57 +/- 0.24 dB, lower next to fixation and increasing
      towards the 50 degree isopter. The medium inter-test variability increases along
      with the perimetric stage :1.57 +/- 0.66 dB for pre-perimetric glaucoma, 2.13 +
      1.04 dB for non-specific defects group, 3.23 + 1.01 dB for the stage 1, 3.52 +
      2.61 dB, for the stage 2, 3.65 + 1.19dB for the stage 3 and 5.82 +/- 1.67dB for
      the stage 4. For the cases of preperimetric glaucoma and non-specific defects, a
      similar profile of variability to the normal subjects can be observed. For the
      stages 2-4, the profile of the areas with maxim inter-test variability moves
      towards the relative scotoma and the surrounding area. CONCLUSIONS: A better
      description of the inter-test variability and the evolution of this intricate
      parameter of the retinal light sensitivity is useful for the differential
      diagnostic between the real change and the "background noise" in early detection
      of the functional progression in glaucoma.

PMID- 24027968
TI  - [Orbit evisceration: retrospective study on a consecutive series of 10 years].
AB  - Exenteration of the orbit is challenging in its anatomical, surgical and
      postsurgical management-related issues. We describe a surgical series of 65
      patients diagnosed at Neurosurgery and Ophthal-mology departments; between 2003
      and 2012, 65 cases with intraorbital tumors were identified and underwent partial
      or total exenteration of the orbit. The most frequent dignosticated tumor which
      underwent exenteration were spinous and basal carcinoma of the orbit (41.5 %)
      followed by neurofibroma The most common preoperative sign was proptosis (100%),
      followed by ocular and orbital pain (6.1%) and visual acuity loss (3.07%).
      Preoperatively signs included alteration of the facial aspect (96.9%),
      behavioural, emotional and social difficulties, especially in young people
      (6,9%). Although there is an extremely mutilant surgical procedure, pain is often
      relieved. Therefore, the surgical aim should be life preserving and relief of
      leading symptoms; estetic aspect of the patients was also one of postoperative
      aims.

PMID- 24027969
TI  - [Retinal and carotid changes in non-alcoholic fatty liver disease].
AB  - This article presents the results of a study on 85 patients with non-alcoholic
      fatty liver disease (NAFLD). We evaluate the retinal vascular changes using
      retinal photography and carotid vascular changes, by ultrasounds, occured in this
      group of patients.

PMID- 24027970
TI  - The community water fluoridation 'debate': scientific consensus versus
      pseudoscientific confusion.

PMID- 24027971
TI  - A review of the effect of vital teeth bleaching on the mechanical properties of
      tooth enamel.
AB  - Tooth whitening is considered the easiest and most cost-effective procedure for
      treating tooth discoloration. Contemporary bleaching agents contain hydrogen
      peroxide as the active ingredient. It is either applied directly or produced from
      its precursor, carbamide peroxide. A review of the published literature was
      undertaken to investigate the potential adverse effects of whitening products on
      dental enamel, with a focus on its mechanical properties and the influence of
      various parameters on study outcomes. There appear to be considerable differences
      in opinion as to whether changes in mechanical properties occur as a result of
      tooth whitening. However, the mechanical property findings of those studies
      appear to be related to the load applied during the indentation tests. Most
      studies which used loads higher than 500mN to determine enamel hardness showed no
      effect of bleaching, whereas those using lower loads were able to detect hardness
      reduction in the surface layer of enamel. In conclusion, bleaching reduces the
      hardness of the enamel surface of enamel, and that is more readily detected with
      instrumented low load testing systems. This hardness reduction may arise due to
      degradation or denaturation of enamel matrix proteins by the peroxide oxidation.

PMID- 24027972
TI  - How long will it last? The expected longevity of prosthodontic and restorative
      treatment.
AB  - With the Internet facilitating access to vast amounts of free information, dental
      practitioners face providing treatment for an increasingly informed public.
      However, the available content is not filtered, and it can be difficult for
      patients to discriminate between research-informed evidence and "glamorised"
      material of dubious origin. Patients reasonably expect a return for their
      investment and want to know how long their treatment will last. Clinicians have
      an obligation to inform their patients so that they can make reasoned decisions
      about treatment options. Longevity data are also informative for health agencies
      setting service schedules for publicly funded treatment, and for determining
      settlements by insurers such as ACC. Historically, much of the prosthodontic
      treatment performed in practice has relied heavily on dogma, low-level anecdotal
      evidence, and clinical case reports. This paper considers the literature on fixed
      and removable prosthodontic restorations and provides a critical review which can
      be used practically as the basis for informing patients, and to assist decision
      makers in making fair and appropriate judgements.

PMID- 24027973
TI  - Dental radiography in New Zealand: digital versus film.
AB  - Digital x-ray systems offer advantages over conventional film systems, yet many
      dentists have not adopted digital technology. OBJECTIVES: To assess New Zealand
      dental practitioners' use of--and preferences for--dental radiography systems.
      DESIGN: Cross-sectional survey. SETTING: General and specialist dental practice.
      PARTICIPANTS AND METHODS: Postal questionnaire survey of a sample of 770 dentists
      (520 randomly selected general dental practitioners and all 250 specialists)
      listed in the 2012 NZ Dental Council Register. MAIN OUTCOME MEASURES: Type of
      radiography systems used by dentists. Dentists' experiences and opinions of
      conventional film and digital radiography. RESULTS: The participation rate was
      55.2%. Digital radiography systems were used by 58.0% of participating dentists,
      most commonly among those aged 31-40 years. Users of digital radiography tended
      to report greater satisfaction with their radiography systems than users
      conventional films. Two-thirds of film users were interested in switching to
      digital radiography in the near future. Reasons given by conventional film users
      for not using digital radiography included cost, difficulty in integrating with
      other software systems, concern about potential technical errors, and the size
      and nature of the intra-oral sensors. CONCLUSION: Many dental practitioners have
      still not adopted digital radiography, yet its users are more satisfied with
      their radiography systems than are conventional film users. The latter may find
      changing to a digital system to be satisfying and rewarding.

PMID- 24027974
TI  - [Observation of size distribution of atmospheric OC/EC in Tangshan, China].
AB  - Atmospheric particulate matter pollution is serious in Tangshan, a heavy
      industrial city of North China. The annual average concentrations of PM1.1,
      PM2.1, PM9.0 and TSP were (75 +/- 43), (106 +/- 63), (221 +/- 100) and (272 +/-
      113) microg x m(-3), respectively, from 2009 to 2011. Carbonaceous aerosols were
      the key components in various size particles. Elemental carbon (EC) accounted for
      9%, 9%, 6% and 4% of PM1.1, PM2.1, PM9.0 and TSP, respectively, meanwhile,
      organic carbon (OC) accounted for 25%, 24%, 16% and 14% of PM1.1, PM2.1, PM9.0
      and TSP, respectively. The concentration spectrum distribution of particulate
      matter and the enrichment amount of the carbonaceous aerosols showed seasonal
      variations. In autumn and winter, the EC and OC concentration in the fine
      particulate matter reached up to (9 +/- 4), (11 +/- 5) and (19 +/- 7), (28 +/-
      10) microg x m(-3), respectively, accounting for 11%, 10% and 26%, 25% of fine
      particles; EC and OC in spring and summer were (5 +/- 2), (5 +/- 1) and (15 +/-
      3), (15 +/- 1) microg x m(-3), respectively, accounting for about 7%, 6% and 26%,
      18% of TSP, respectively.

PMID- 24027975
TI  - [Changing characteristics of the main air pollutants of the Dongling Mountain in
      Beijing].
AB  - Concentrations of SO2, NO(x), O3 and PM2.5 were observed from August 2009 to June
      2011 in Beijing forest ecology observation site which locates at the Dongling
      Mountain of Beijing. Monthly, seasonal variation and statistical diurnal
      variation characteristics of air pollutants were analyzed. Besides, the influence
      of transportation to air pollutants was also discussed combined with the back
      trajectories of air mass. The average concentrations of NO, NO2, NO(x), O3, SO2
      and PM2.5 were (2.0 +/- 1.6), (13.2 +/- 7.2), (15.3 +/- 8.2), (61.0 +/- 19.6),
      (3.6 +/- 3.6) and (35.6 +/- 32.0) microg x m(-3), respectively. The concentration
      of pollutants in Beijing forest ecology observation site was lower than that in
      rural observation site in Beijing. The highest value of NO(x) appeared in autumn
      while the lowest appeared in summer, and concentrations of NO(x) in autumn and
      summer were (17.0 +/- 8.0) microg x m(-3) and (13.8 +/- 4.1) microg x m(-3),
      respectively. Concentrations of O3 in spring and summer were higher than those in
      autumn and winter. The highest concentration of O3 appeared in June. The
      concentration of SO2 in winter was the highest, and this concentration was 2.7
      times to the lowest concentration in summer. The highest concentration of PM2.5
      appeared in summer and was 56.4 microg x m(-3). There were obvious diurnal
      variation of NO(x), O3 and SO2. There are two peaks of NO(x) have been observed,
      however there are only one peak of O3 and SO2 has been observed. There was no
      obvious diurnal variation of PM2.5 to other pollutants.

PMID- 24027976
TI  - [Characteristic comparative study of particulate matters in Beijing before and
      during the Olympics].
AB  - Two city ecosystem research stations were selected for continuous monitoring of
      atmospheric fine particulate matter (PM2.5) concentration from June to September
      2008, when the Beijing Olympic Games was held. The relationship between
      meteorological factors, artificial control management measures and PM2.5 dynamic
      characteristics were analyzed. The results showed that the daily average
      concentration of PM2.5 at RCEES Station, which is near the 5th North Ring, was
      0.067 mg x m(-3) during the study period, and the particle concentration during
      the Olympic Games was 0.060 mg x m(-3), which was decreased by about 26% compared
      with the content before the Olympic Games (0.081 mg x m(-3)). As for JX Station
      located in the 2th South Ring, its daily average concentration of PM2.5 was 0.078
      mg x m(-3). Similar to RCEES Station, PM2.5 average content during the Olympic
      Games (0.069 mg x m(-3)) was 27% lower compared with the content before the
      Olympic Games (0.095 mg x m(-3)). Two peaks could be found when daily
      distribution of PM2.5 was displayed, one appeared between 08:00 and 10:00 (the
      average content for RCEES and JX were 0.068 and 0.089 mg x m(-3), respectively),
      and the other appeared at 20:00-22:00, which could be attributed to traffic
      emission and road dust pollution, especially the emission from the growing number
      of cars in rush hours. Meteorological condition during the whole period was
      typical in summer in Beijing with both high temperature and humidity. Correlation
      analysis revealed that the concentrations of PM2.5 had a positive correlation
      with the air temperature (P < 0.01), while it had no significant relationship
      with wind speed, relative humidity or precipitation (P > 0.05). Our monitoring
      results suggested that the artificial air pollution control strategies were
      effective measures for air pollution control during 2008 Beijing Olympic Game.

PMID- 24027977
TI  - [Characteristics and impact factors of O3 concentrations in mountain background
      region of East China].
AB  - The O3 concentrations were measured online from March 2011 to February 2012 at
      the national atmospheric background monitoring station in Wuyishan of Fujian
      Province to discuss the characteristic of O3 concentrations and the impact
      factors in forest and mountain background region of East China. HYSPLIT (Hybrid
      Single Particle Lagrangian Integrated Trajectory) Model was used to investigate
      the potential sources of particulates during the pollution episodes. The results
      showed that the background concentration of O3 was (87.9 +/- 34.1) microg x m(
      3). Seasonal variations of O3 loadings were observed, and the loadings decreased
      in the order spring > autumn > summer > winter. Analysis of correlation between
      O3 and other gas pollutants suggested regional transportation, stratospheric
      injection and photochemical production were the major sources of O3 in Wuyishan
      background station. The episodes were related with transportations of air parcel
      from Yangtze River Delta region, Pearl River Delta region and the high altitudes.

PMID- 24027978
TI  - [Studies on the size distribution of airborne microbes at home in Beijing].
AB  - The effect of airborne microbes on human health not only depends on their
      compositions (genera and species), but also on their concentrations and sizes.
      Moreover, there are different mechanisms of airborne microbes of different sizes
      with different effects on human health. The size distributions and median
      diameters were investigated in detail with imitated six-stage Andersen sampler in
      31 selected family homes with children in Beijing. Results showed that there was
      similar distribution characteristics of airborne microbes in different home
      environment, different season, different child's sex, and different apartment's
      architecture, but different distribution characteristics between airborne
      bacteria and fungi were observed in family homes in Beijing. In general, although
      airborne bacteria and fungi were plotted with normal logarithmic distribution,
      the particle percentage of airborne bacteria increased gradually from stage 1 (>
      8.2 microm) to stage 5 (1.0-2.0 microm), and then decreased dramatically in stage
      6 (< 1.0 microm), the percentage of airborne fungi increased gradually from stage
      1 to stage 4 (2.0-3.5 microm), and then decreased dramatically from stage 4 to
      stage 6. The size distributions of dominant fungi were different in different
      fungal genera. Cladosporium, Penicillium and Aspergillus were recorded with
      normal logarithmic distribution, with the highest percentage detected in stage 4,
      and Alternaria were observed with skew distribution, with the highest percentage
      detected in stage 2 (5.0-10.4 microm). Finally, the median diameters of airborne
      bacteria were larger than those of airborne fungi, and the lowest median diameter
      of airborne bacteria and fungi was found in winter, while there were no
      significant variations of airborne bacterial and fungal median diameters in
      spring, summer and autumn in a year in this study.

PMID- 24027979
TI  - [Emission factors of polycyclic aromatic hydrocarbons (PAHs) in residential coal
      combustion and its influence factors].
AB  - As the emission source of polycyclic aromatic hydrocarbons (PAHs), domestic coal
      combustion has attracted increasing attention in China. According to the coal
      maturity, combustion form and stove type associated with domestic coal
      combustion, a large-size, full-flow dilution tunnel and fractional sampling
      system was employed to collect the emissions from five coals with various
      maturities, which were burned in the form of raw-coal-chunk (RCC)/honeycomb-coal
      briquettes (HCB) in different residential stoves, and then the emission factors
      of PAHs (EF(PAHs)) were achieved. The results indicate that the EF(PAHs) of
      bituminous coal ranged from 1.1 mg x kg(-1) to 3.9 mg x kg(-1) for RCC and 2.5 mg
      x kg(-1) to 21. 1 mg x kg(-1) for HCB, and the anthracite EF(PAH8) were 0.2 mg x
      kg(-1) for RCC and 0.6 mg x kg(-1) for HCB, respectively. Among all the influence
      factors of emission factors of PAHs from domestic coal combustion, the maturity
      of coal played a major role, the range of variance reaching 1 to 2 orders of
      magnitude in coals with different maturity. Followed by the form of combustion
      (RCC/HCB), the EF(PAHs) of HCB was 2-6 times higher than that of RCC for the same
      geological maturity of the coal. The type of stove had little influence on
      EF(PAHs).

PMID- 24027980
TI  - [Experimental research on alcohols, aldehydes, aromatic hydrocarbons and olefins
      emissions from alcohols fuelled vehicles].
AB  - Using two vehicles fuelled with pure gasoline, M15, M30 and pure gasoline, E10,
      E20 separately, 25 degrees C normal temperature type I emission test, -7 degrees
      C low temperature type VI emission test and type IV evaporation emission test
      were carried out. FTIR, HPLC and GC-MS methods were utilized to measure alcohols,
      aldehydes, aromatic hydrocarbons and olefins emissions. The test results indicate
      that at the low as well as normal ambient temperature, as the alcohols proportion
      increasing in the fuel, unburned methanol, formaldehyde, acetaldehyde increase
      proportionally, benzene, toluene, ethylene, propylene, 1,3-butadiene and
      isobutene decrease slightly. The unregulated emissions at the low ambient
      temperature are significantly higher than those at the normal ambient
      temperature. The difference of HC emissions in the entire process of evaporative
      emission tests of E10, gasoline and M15 fuels is slight. There is a small
      difference of unregulated emissions in the diurnal test of three fuels.

PMID- 24027981
TI  - [Combination process of microwave desorption-catalytic combustion for toluene
      treatment].
AB  - Using activated carbon as adsorbent, toluene waste gas was treated by adsorption
      process. After the adsorption process was completed, the adsorbent was desorbed
      by microwave irradiation; then Cu-Mn oxide composite catalysts were prepared by
      impregnation and the desorbed toluene gas was treated by catalytic combustion so
      as to completely purify the pollutant. The concentration of toluene was measured
      by gas chromatography (GC). The results indicated that it is feasible to add air
      to provide oxygen to the desorbed gas after the completion of the desorption
      process, in order to achieve the catalytic combustion; the ratio of desorbed gas
      and air was 1 : 1 (volume ratio), and the corresponding catalytic space velocity
      was 2.67 s(-1). Desorption temperature could affect the concentration of toluene
      in the desorption gas thereby affecting the catalytic combustion efficiency; the
      results indicated that 400 degrees C was an appropriate temperature for desorbing
      the activated carbon. When the catalytic combustion was kept at 300 degrees C,
      the final toluene treatment efficiency was higher than 90%, which was higher than
      95% during the most time of the treatment process.

PMID- 24027982
TI  - [Removal of BTEX by a biotrickling filter and analysis of corresponding bacterial
      communities].
AB  - The pre-acclimated microbial consortium and the activated sludge were used as
      start inoculums of a bench-scale biotrickling filter (BTF). The performance of
      the biotrickling filter on the removal of BTEX mixture was evaluated, and the
      changes in the bacterial community structure of the BTF were analyzed by PCR-DGGE
      technique. The results showed that the BTF could be acclimated within a short
      time, the biomass that adhered to the surface of packing materials increased
      rapidly from 5.7 mg x g(-1) at 10th day to 112 mg x g(-1) at 30th day. BTF could
      simultaneously remove all components of the BTEX mixture efficiently. The maximum
      removal capacity of the BTF was 216.6 g x (m3 x h)(-1), which was achieved with
      an inlet loading rate of 269.7 g x (m3 x h)(-1) and an empty bed retention time
      (EBRT) of 39 s. DGGE analysis indicated that the dominant microorganisms may be
      derived from the pre-acclimated microbial consortiums rather than the activated
      sludge. Although the bacterial community changed with run time, the spatial
      distribution was very uniform.

PMID- 24027983
TI  - [Source profile of volatile carbonyl compounds in wastewater treatment plant of
      an oil refinery].
AB  - An observation was conducted at the wastewater treatment plant in a refinery in
      Guangdong province, using the PFPH-GC/MS method to analyze the composition and
      the concentration of volatile carbonyl compounds. The emission characteristics
      and the atmospheric chemical reactivity of these compounds were also studied. The
      results showed that 20 kinds of carbonyl compounds were detected with a
      concentration range of 0 to 68.80 microg x m(-3). The mean value of total
      concentration in all processing unit was (253.02 +/- 124.5) microg x m(-3).
      Background corrected concentrations showed that for each of the 6 treatment units
      of the plant, over 90% of the volatile carbonyl emissions were contributed by 14
      of the 20 volatile carbonyl compounds, among which aldehyde was the most abundant
      with an average concentration of (44.74 +/- 20.89) microg x m(-3), followed by 2
      butanone and acetaldehyde with average concentrations of (30.47 +/- 12.94) microg
      x m(-3) and (23.51 +/- 14.57) microg x m(-3), respectively. Several molecular
      markers were identified based on the analysis of the chemical activities and
      atmospheric lifetimes of the 20 carbonyl compounds. Finally, a source profile was
      established for the plant.

PMID- 24027984
TI  - [Distribution and air-sea fluxes of methane in the Yellow Sea and the East China
      Sea in the spring].
AB  - A survey was carried out in the Yellow Sea and the East China Sea from March 17
      to April 06 of 2011. Dissolved CH4 in various depths were measured and sea-to-air
      fluxes were estimated. Methane concentrations in surface and bottom waters ranged
      between 2.39-29.67 nmol x L(-1) and 2.63-30.63 nmol x L(-1), respectively.
      Methane concentrations in bottom waters were slightly higher than those in
      surface waters, suggesting the existence of methane source in bottom waters or
      sediments. The horizontal distribution of dissolved CH4 showed a decrease from
      the river mouth to the open sea, and was influenced by the freshwater discharge
      and the Kuroshio intrusion. Surface methane saturations ranged from 93%-1 038%.
      Sea to air CH4 fluxes were (2.85 +/- 5.11) micromol x (m2 x d)(-1) (5.18 +/-
      9.99) micromol x (m2 x d)(-1) respectively, calculated using the Liss and
      Merlivat (LM86), the Wanninkhof (W92) relationships and in situ wind speeds, and
      estimated emission rates of methane from the East China Sea and the Yellow Sea
      range from 7.05 x 10(-2) - 12.0 x 10(-2) Tg x a(-1) and 1.17 x 10(-2) - 2.20 x
      10(-2) Tg x a(-1), respectively. The Yellow Sea and East China Sea are the net
      sources of atmospheric methane in the spring.

PMID- 24027985
TI  - [Study on seasonal characteristics of thermal stratification in lacustrine zone
      of Lake Qiandao].
AB  - Lake Qiandao is a typical subtropical man-made reservoir in China. The
      investigation on the seasonal and vertical dynamics of water temperature,
      dissolved oxygen (DO), pH value, turbidity, photosynthetic available radiation
      (PAR) and chlorophyll a was conducted in 2011 in order to find out the physical
      characteristics of Lake Qiandao. The average surface water temperature ranged
      from 10.4 to 32.7 degrees C. A monomictic thermal stratification was observed in
      Lake Qiandao, initiating in April and lasting until December. The results showed
      that thermal stratification had influences on vertical distribution of DO, pH
      value, turbidity, PAR and chlorophyll a. Very strong stratification of DO was
      found, inducing lower oxygen concentration in the thermocline layer and temporal
      hypoxia in the bottom water. The maximum turbidity was found in the thermocline
      layer and the precipitation affected the surface turbidity value. Moreover, the
      chlorophyll a concentration was higher in the surface water and lower in the
      bottom water as found in this study, implying that water quality was affected by
      stratification. Besides, the maximum photosynthesis rate and algal growth rate
      were found at the depth 5-10 m below the water surface. Therefore, the results
      can provide theoretical support for the sampling and analysis of algal blooms in
      Lake Qiandao.

PMID- 24027986
TI  - [Effects of land use structure on water quality in Xin'anjiang River].
AB  - Take Xin'anjiang upstream watershed as a case study. Based on data of
      interpreting TM orthophoto images and water quality monitoring in May 2010, the
      land use map of Xin'anjiang River, which was categorized to cultivated land,
      forestland, grassland, water body, building site, was obtained. Using ArcGIS
      hydrological and spatial analysis function, Xin'anjiang River was divided into
      eight sub-watersheds, and its watershed land use structure was analyzed. The
      water quality parameters such as TN, TP, permanganate index, fecal coliform
      bacteria were monitored from Jan 2010 to Dec 2010. The relations between water
      quality and land use were analyzed. The results showed that TN and NH4(+) -N had
      a significant temporal variation: dry season > wet season > normal river flow
      period, but other parameters did not vary significantly. In the space, Yuliang
      and Pukou were the most serious pollution sites. Cultivated land, water body,
      building site had a positive impact on water quality parameters, while there were
      negative correlation between the forestland and grassland. Annually, cultivated
      land had the most significantly important effect on TN, NH4(+) -N and
      permanganate index, and grassland had the most significantly important effect on
      TP. Cultivated land had the most prominently important impact on water quality
      parameters in dry season and wet season. What's more, in the normal river flow,
      cultivated land, grassland and forestland had the most remarkably important
      influence on TN, TP and fecal coliform bacteria respectively.

PMID- 24027987
TI  - [Canonical correspondence analysis between phytoplankton community and
      environmental factors in macrophtic lakes of the middle and lower reaches of
      Yangtze River].
AB  - The phytoplankton communities in 4 macrophtic lakes (Longgan Lake, Liangzi Lake,
      Futou Lake and Baoan Lake) in Middle-Lower Yangtze Plain were investigated in
      September 2011, and 7 phylum and 231 species of phytoplankton were detected in
      the waters. The results indicated that phytoplankton was mainly composed of
      Cyanophyta, Bacillariophyta and Chlorophyta. The four lakes were mesotrophic. And
      the main phytoplankton was Phormidium foveolarum, Synedra ulna, Phormidium tenu
      and Tribonema minus. The relationships between the distribution of phytoplankton
      and environmental factors in each sampling site were studies by canonical
      correspondence analysis. The results demonstrated that pH and Total phosphorus
      are the key factors for the distribution of phytoplankton communities in 4
      typical macrophtic lakes in Middle-Lower Yangtze Plain.

PMID- 24027988
TI  - [Microbial bioavailability of dissolved nucleic acids across the estuarine
      salinity gradient].
AB  - As an important component of dissolved organic matter (DOM), nucleic acids (DNA
      and RNA) are essential nutrient and energy sources in aquatic microbial food web.
      Therefore, it is important to understand the bioavailability of nucleic acids.
      The bioavailability of nucleic acids was investigated by a batch of incubation
      experiments, adding fish DNA and yeast RNA into water samples with different
      salinity collected from the Yangtze River estuary in the spring of 2012.
      According to the results, 20%-50% of dissolved DNA was transformed into
      particulate DNA quickly with the conversion rates increasing with salinity, only
      10% dissolved RNA was transformed into particulate RNA and the salinity had no
      effect on the conversation rates. In each incubation experiment, the microbial
      utilization kinetic curves of dissolved nucleic acids were fitted to the Sigmoid
      model. There were lag periods of 30-80 hours followed by the rapid utilization
      phase and then the stagnation phase. The results also showed that the bacteria in
      seawater had higher maximum utilization rate than the bacteria in estuarine and
      fresh water. Dissolved nucleic acids spiked in estuarine water can be bound to
      colloids and particles at some extent, only those free dissolved or enzymatically
      hydrolysable forms are bioavailable. The percentage of bioavailable RNA (80%-90%)
      was significantly higher than that of bioavailable DNA and it did not change
      significantly with salinity while the percent of bioavailable DNA decreased from
      78% to 50% with salinity. Therefore, the speciation and bioavailability are
      significantly different between DNA and RNA across the estuarine salinity
      gradient.

PMID- 24027989
TI  - [Elementary quantitative study on factors of phytoplankton bloom].
AB  - This study investigated the effect quantitatively on phytoplankton population by
      various factors such as sinking velocity, diffusivity, growth, mortality and
      water depth, through both numerically and theoretical methods, then proposed an
      initial judgment criterion for estimating phytoplankton population development.
      To the conventional simplification about even growth rate and vertical turbulent
      diffusivity, which is not consistent with the fact, this study investigated the
      influence by the asymmetric growth rate, as a result of light attenuation and
      nutrient limit, and uneven vertical turbulent diffusivity. It was shown that the
      'shade effect' by light attenuation and nutrient flux limit both led.
      phytoplankton population from blooming or collapsing to quasi-steady condition.
      The uneven vertical turbulent diffusivity influenced the phytoplankton population
      by l/H which is upper euphotic layer depth by water depth. The influence is not
      apparent only if the water depth is large enough while l/H is small. Hence even
      vertical turbulent diffusivity can be utilized approximately in very shallow
      lakes.

PMID- 24027990
TI  - [Spatiotemporal succession of algae functional groups and the influence of
      environment change in a deep-water reservoir].
AB  - Algae functional group has become an important theory and method of algae
      research in recent years. In order to explore the spatiotemporal succession of
      algae functional groups and the influence of environment change, water samples
      were collected in August, 2011 from a deep-water reservoir in Northwest China.
      The research combined the methods of on-line monitoring and laboratory analysis.
      The results showed that there were 10 functional groups of algae in the
      reservoir. They were designated as B, D, P, X1, X3, F, G, J, L(M) and MP.
      Wherein, the groups B, P, F, X1, MP, D and J were comparatively common functional
      groups, and the groups X3, G and L(M) were less common. The populations of groups
      B, D, P, X1 and X3 were larger than those of the others. Besides, the analysis of
      changes in the environment factors suggested that temperature was the most
      important factor influencing the spatiotemporal succession of algae functional
      groups. The strategy of algal growth followed the law: R/CR in spring --> CR/C in
      late spring and early summer C/CR/R/CS/S in late summer and early autumn --> CR/R
      in late autumn and winter. The purpose of this article is to provide theoretical
      support for water withdrawal safety in deep-water reservoirs.

PMID- 24027991
TI  - [Hyperspectral remote sensing of total suspended matter concentrations in Lake
      Taihu based on water optical classification].
AB  - Four field investigations were carried out in the Taihu Lake for collecting in
      situ observation data in Nov. 2008, Apr. 2009, May and Aug. 2010. On the basis of
      water optical classification, different retrieval algorithms were developed,
      specific for different types of waters. Based on the preformance of each model
      comparion in each type of waters, the optimal models obtained were (1) the band
      ratio model for Type 1 water; (2) the semi-analysis algorithm model 2 for Type 2
      water; (3) the first-order differential model for Type 3 water. Meanwhile, an
      optimal retrieval model was also established using the same collection of
      calibration data. Some comparisons were done between the developed models for the
      classified and non-classified waters. The comparison results showed that the
      models for the classified waters had better performances than that for the non
      classified water, in both the retrieval accuracy and the model stability. Then,
      analyses of the optical classification leading to the accuracy decrease of the
      semi-analysis algorithm model were processed. Finally, the results of this study
      in hyperspectral remote sensing date showed a great application potential by
      analysis. The findings of this study are significant for promoting the
      development of water color remote sensing for optically complex turbid inland
      waters.

PMID- 24027992
TI  - [Application of subwet model in the design of constructed wetland].
AB  - The mechanism of horizontal subsurface-flow constructed wetland (HSSF CW) and its
      design guidelines were introduced for the design of a constructed wetland. A
      numerical model Subwet was proposed to aid the design of constructed wetland. The
      design of a horizontal subsurface-flow wetland was simulated by utilizing Subwet
      model. The treatment efficiency for a year round operation was obtained from the
      modelling. The factors which have effects on treatment efficiencies were analyzed
      and investigated in this study. The recommendations on optimizing and improving
      the HSSF CW design were provided. This case study of Subwet model demonstrated
      the applicability of this model in the design of constructed wetland. It can
      provide theoretical basis for the design of constructed wetland.

PMID- 24027993
TI  - [Allelopathic effect of Nelumbo nucifera stem and leaf tissue extract on the
      growth of Microcystis aeruginosa and Scenedesmus quadricanda].
AB  - Effects of Nelumbo nucifera stem and leaf tissue extract on the growth of
      Microcystis aeruginosa and Scenedesmus quadricanda were studied to verify its
      potential in entriphication control. Five concentrations of Nelumbo nucifera stem
      and leaf tissue extract were chosen to compare their inhibitory effects on the
      growth of Microcystis aeruginosa and Scenedesmus quadricanda. The result showed
      that the leaf extract inhibited the algae bloom more effectively than the stem
      extract on the whole. When the leaf extract normality was 25 g x L(-1), the
      highest inhibition rate of Microcystis aeruginosa and Scenedesmus quadricanda was
      71.33% and 78.14%, respectively, while for the stem extract, the values were
      49.78% and 52.14%. Propanamide was found in both the stem and leaf tissue
      extracts of Nelumbo nucifera by GC-MS analysis, with concentrations of 1.1 mg x
      L(-1) and 0.2 mg x L(-1), respectively. The EC50 values of the two kinds of algae
      were calculated by the probability method.

PMID- 24027994
TI  - [Influence of Vallisneria spiralis on the physicochemical properties of black
      odor sediment in urban sluggish river].
AB  - Using Indoor simulation method, the effect of Vallisneria spiralis on the
      physicochemical propertise of black and stink sediment was investigated. The
      surface sediment of urban sluggish river which had been heavily polluted was used
      as material in the study. The results showed that the redox environment of the
      sediment was significantly improved by Vallisneria spiralis. During the
      experiment, the Eh of surface sediment rose from -70 mV to 90 mV. The ferrous
      content was reduced by 25% in the experiment group while increased by 38% in the
      control group; the organic matter was decomposed effectively, prevented from
      natural decomposition to the smelly substances. There was a 3 mm thick greyish
      yellow oxide layer after 7 days in the experimental group, and the oxide layer
      gradually thickened over time. The thickness of the oxide layer reached 11 mm at
      the end of the experiment, and no significant odor was detected. On the contrary,
      the oxide layer in the control group was only 1 mm thick and the thickness
      remained unchanged. Meanwhile, an obnoxious odor existed during the whole
      experiment. The roots of Vallisneria spiralis had significant influence on the
      porosity of sediment. On one hand, the densification of sediment could be
      improved by Vallisneria spiralis. On the other hand, Vallisneria spiralis was
      able to change the state of the surface sediment flows, reduce the erosion of
      river sediment and inhibit the transfer of black-odor substances, which has a
      positive ecological meaning.

PMID- 24027995
TI  - [Removal of Cr(VI) by iron filings with microorganisms to recover iron
      reactivity].
AB  - The reduction of Cr(VI) by iron filings and microorganisms was carried out during
      our investigation. Effects of factors (e. g. temperature, initial pH, iron
      filings loadings, inoculum size, initial concentration of Cr(VI) and other ions)
      on Cr(VI) reduction were studied, and the X-ray photoelectron spectroscopy (XPS)
      was applied to explore elements composition on the surface of iron filings.
      Experimental results revealed a promotion of Cr(VI) reduction by iron filings
      with the presence of microorganisms, and the Cr(VI) removal was complete within
      18 h. Results showed the Cr(VI) reduction preferred a higher temperature within
      the range of 25-42 degrees C and the optimum initial pH was supposed to be 5.8.
      The efficiency of Cr(VI) reduction was increased with increasing amounts of iron
      filings and microorganisms, and was decreased with the increasing initial
      concentration of Cr( VI). Mn2+, Zn2+, Co2+, Cu2+ and Ni2+ ions could cause
      varying degrees of inhibition of Cr(VI) reduction, and among these ions, the
      effect of Mn2+ was the smallest and that of Ni2+ was the highest.
      Characterizations with XPS indicated the deposition of Cr element on iron filings
      surface in forms of Cr(III) and Cr(VI), as the Cr2p3/2 region could be decomposed
      into two peaks at (576.8 +/- 0.1) eV and (578.1 +/- 0.1) eV. Furthermore, Cr(III)
      was most likely to be in the form of Cr(OH)3 or Fe(x)Cr(1-x)(OH)3.

PMID- 24027996
TI  - [Degradation of phenol with a Fe/cu-catalytic heterogeneous-Fenton process].
AB  - The catalysts of Fe/AC, Cu/AC and Fe-Cu/AC with active carbon as support were
      prepared by a wet impregnation method, and were characterized using X-ray
      diffraction (XRD), nitrogen adsorption and X-ray photoelectron spectroscopy (XPS)
      measurements; the catalytic heterogeneous-Fenton processes of phenol degradation
      with these catalysts were also investigated, and the degradation mechanism was
      discussed with analysis of intermediate products and electron spin resonance
      (ESR) measurement. The results showed that the active component states varied in
      different catalysts; CuO was the main state of Cu in Cu/AC and Fe exhibited
      various valence states in Fe/AC. The degradation rate of phenol with Fe/AC, Cu/AC
      and Fe-Cu/AC as catalyst in the initial 60 min reached 96.7%, 77.5% and 99%,
      respectively; the dissolution of a little active-component metal was found in
      Cu/AC and Fe-Cu/AC, but little Fe in Fe/AC was dissolved; the degradation of
      phenol was performed by heterogeneous Fe/AC instead of dissolved Fe, and the
      degradation rate was above 93% after Fe/AC was used for three cycle runs, showing
      a stable catalytic activity. Under the optimum conditions of pH = 3, T = 303 K,
      and 4.38 mmol x L(-1) H2O2, the removal of phenol and TOC in the Fe/AC-catalytic
      Fenton process could reach 97% and 53%, respectively, while little phenol was
      degraded without catalyst. The ESR results indicated that hydroxyl radical was
      produced in the catalytic decomposition of H2O2 with Fe/AC as catalyst,
      demonstrating that the degradation of phenol mainly followed an oxidation pathway
      of hydroxyl radical; intermediates such as hydroquinone, p-benzenequinone and
      catechol were obtained, and the results showed thatortho- and para-substitution
      reaction by hydroxyl might be the main mechanism of phenol oxidation.

PMID- 24027997
TI  - [Effect of different forms of inorganic nitrogen on the photodegradation of
      antipyrine in water].
AB  - The photodegradation performance and mechanisms of antipyrine (ANT, a member of
      anti-inflammatory analgesics) under simulated irradiation using a 300 W Xenon
      lamp were explored in this study. And the variation of the photodegradation of
      ANT in the presence of different forms of nitrogen and different pE values in the
      aqueous environment were also investigated. The results demonstrated that ANT
      photodegradation proceeds via pseudo first-order kinetics in all cases.
      Photodegradation of ANT in water occurs through direct photodegradation and self
      sensitization via reactions with hydroxyl radical (*OH) and singlet oxygen (1O2).
      Presence of different forms of inorganic nitrogen (NH4+, NO2- and NO3-) showed
      rather different effects. At low pE value (< 5), NH4+ was the main form of
      inorganic nitrogen, and little effect was observed on ANT photodegradation. With
      the increase of pE value from 4.82 to 6.85, nitrogen form changed from NH4+ to
      NO2- accordingly, and the inhibiting effect increased gradually due to their
      competitive absorption for the irradiation and NO2- acting as a scavenger of *OH.
      At pE 6.85, NO2- was the main form of inorganic nitrogen, which showed a maximum
      inhibiting rate of 35.31%. When the pE value continued to increase from 6.85 to
      8.15, the nitrogen form changed from NO2- to NO3-, and the suppression effect on
      ANT photodegradation decreased.

PMID- 24027998
TI  - [Degradation mechanisms of dimethyl phthalate in the UV-H2O2 system].
AB  - To investigate the photodegradation process of dimethyl phthalate (DMP) in the
      ultraviolet light (UV)-H2O2 system, mass spectrometer was used to identify
      degradation products and further more, to speculate the possible mechanisms of
      degradation process. Experimental results showed that the degradation efficiency
      of 10 mg x L(-1) DMP reached 92.3% in 90 minutes in the UV-H2O2 system, and the
      more H2O2 was added, the faster DMP decomposed. The pH of DMP solution decreased
      from the initial 6.5 to 4.98, because of the generating of organic phenolic acids
      and small acid molecules generated by the degradation of DMP. By the GC/MS as
      well as LC/MS analysis, degradation products of the DMP in the UV-H2O2 system
      were thought to comprise six categories, from which we could infer that
      hydrolysis occurs simultaneously on the two side chains of the DMP, generating
      phthalic acid that can quickly change to the more stable terephthalic acid. In
      addition, DMP could also occur benzene ring replacement as well as the ring
      condensed of the side chains. Finally, by the role of *OH, DMP and its aromatic
      intermediates occurred ring-opening reaction, and benzene ring was destroyed and
      generated organic acids of small molecular, which was further mineralized to CO2
      and water.

PMID- 24027999
TI  - [Adsorption of Cd2+ ions in aqueous by diamine-modified ordered mesoporous SBA-15
      particles].
AB  - Highly ordered channel structure SBA-15 was widely concerned as new adsorbents in
      environmental protection, in order to increase its heavy metal ions adsorption
      ability from aqueous solution, the diamine -modified porous silicate SBA-15 was
      synthesized by a hydrothermal grafting method and characterized by TEM, X-ray
      diffraction, FTIR and N2 adsorption-desorption. The SBA-15 and modified SBA-15
      samples were used as sorbents to adsorb Cd(II) ions from aqueous solution. The
      effect of experimental parameters, such as pH, contact time, sorbent dosage and
      temperature were examined, and the maximum adsorption amount was also calculated.
      The results showed that under same conditions, the Cd(II) removal rate was higher
      for 2N-SBA-15 than that of the unmodified SBA-15. The adsorption process was
      controlled by system pH. The highest removal rate could reached about 95% after
      pH was higher than 4. Adsorption equilibrium was reached within 30 minutes,and
      more than 95% Cd2+ was adsorbed when 7.5-20 mg sorbent was added into 100 mL
      solution contained 25 mg x L(-1) Cd2+. The adsorption capacity increased from
      94.73% to 98.22% with temperature increased from 25 degrees C to 35 degrees C.
      The Langmuir model can be used to describe adsorption isotherms. The adsorption
      capacity of Cd2+ was 0.9 mmol x g(-1) which is comparable to the adsorption
      capacity of various adsorbents reported in the literature, and 0.1 mol x L(-1)
      HCl could remove nearly 93% Cd2+ from 2N-SBA-15 particles. Based on the
      thermodynamic, pH, XPS and Zeta potential analysis results in this study, it
      could be concluded that the adsorption process was an endothermic and spontaneous
      reaction which contained physical adsorption, ion exchange and chelating reaction
      etc. The study indicated that the diamine -modified ordered mesoporous material
      SBA-15 is a potential sorbent which could be used for the aqueous Cd2+ removal.

PMID- 24028000
TI  - [Surface organic modification of acid vermiculite and its adsorption of
      hydrophobic micro pollutants in aqueous solutions].
AB  - To solve the problems of intercalated organoclay such as low surface area and
      inhomogeneous organic loading, natural vermiculite was activated by acid leaching
      and then modified by trimethylchlorosilane (CTMS) and triethylchlorosilane
      (CTES). The modified materials were characterized by FTIR, BET, SEM and TG.
      Experimental results indicated that the surface area of the modified acid
      vermiculite (361.0 m2 x g(-1)) was much larger than that of the intercalated
      organovermiculite (6.0 m2 x g(-1)), moreover, the organic groups were grafted
      onto the surface covalently. Diethyl phthalate (DEP), a typical hydrophobic micro
      organic pollutant, was used to test the adsorption capacity of different
      adsorbents. The adsorption amounts of DEP were 63.7, 51.2 and 15.7 mg x g(-1) for
      CTES, CTMS and intercalated organovermiculite in this study, respectively. The
      high organic affinity of modified acid vermiculite was due to both the bigger
      surface area and the homogeneous organic loading. The adsorption kinetics was
      found to follow the pseudosecond-order model. The isotherms exhibited linear
      characteristics and could be described by Henry and Freundlich equations,
      indicating that the partition process is the main control mechanism of the
      removal of DEP.

PMID- 24028001
TI  - [Preparation of porous ceramics based on waste ceramics and its Ni2+ adsorption
      characteristics].
AB  - The preparation conditions of porous ceramics were determined by SEM, XRD and FT
      IR characterizations as well as the nickel removal ability of porous ceramics to
      be: the mass fraction w of sesbania powder doped was 4%, and the calcination
      temperature was 800 degrees C. SEM and pore structure characterization
      illustrated that calcination caused changes in the structure and morphology of
      waste ceramics. With the increase of calcination temperature, the specific
      surface area and pore volume decreased, while the aperture increased. EDS
      analyses showed that the main elements of both the original waste porcelain
      powder and the porous ceramics were Si, Al and O. The SEM, XRD and FT-IR
      characterization of porous ceramics illustrated that the structure of porous
      ceramics was stable before and after adsorption. The series of experiments of
      Ni2+ adsorption using these porous ceramics showed that when the dosage of porous
      ceramics was 10 g x L(-1), the adsorption time was 60 min, the pH value was 6.32,
      and the concentration of nickel-containing wastewater was below 100 mg x L(-1),
      the Ni2+ removal of wastewater reached 89.7%. Besides, the porous ceramics showed
      higher removal efficiency on nickel in the wastewater. The Ni(2+)-containing
      wastewater was processed by the porous ceramics prepared, and the adsorption
      dynamics and adsorption isotherms of Ni2+ in wastewater by porous ceramics were
      investigated. The research results showed that the Ni2+ adsorption process of
      porous ceramics was in accordance with the quasi second-order kinetic model (R2 =
      0.999 9), with Q(e) of 9.09 mg x g(-1). The adsorption process can be described
      by the Freundlich equation and Langmuir equation, and when the temperature
      increased from 20 degrees C to 40 degrees C, the maximum adsorption capacity Q(m)
      increased from 14.49 mg x g(-1) to 15.38 mg x g(-1).

PMID- 24028002
TI  - [Perchlorate removal from underground water by anaerobic biological reduction
      with bark].
AB  - Batch experiments were conducted to check the feasibility of perchlorate removal
      from underground water with bark as a carbon source and reaction media, the
      effect of bark dosage, temperature and initial perchlorate concentrations on
      perchlorate reduction were also investigated. The results indicated that compared
      to corn cob, sweet potato and potato, bark in combination with perchlorate
      reducing microorganisms (PRMs) can efficiently achieve perchlorate removal from
      underground water, the concentrations of dissolved organic carbon (DOC) which was
      available to PRMs was the limiting factor that affected the perchlorate removal
      efficiency. Degradation of 10 mg perchlorate needed to consume 35-40 mg DOC when
      using bark as the solid carbon source. The removal rate of perchlorate was
      increased by about 3 fold when the bark dosage was increased from 1:500 to 3:500;
      however, further increase of solid-liquid ratio (over 5:500) provided no further
      benefit to the perchlorate reduction rate. The rate constant reached 1.365 mg x
      (L x d)(-1) at (38 +/- 1) degrees C which was the highest in the batch
      experiments. The activation energy was 31.08 kJ x mol(-1). Anaerobic biological
      reduction supported by bark had a good impact on the water quality; the high
      perchlorate concentration did not cause substrate inhibition.

PMID- 24028003
TI  - [Experimental study on the remediation of chromium contaminated groundwater with
      PRB media].
AB  - Due to the surface reaction between zero-valent iron and Cr(VI), iron cannot be
      fully utilized in the Fe(0)-Permeable Reactive Barrier(PRB), and the PRB is prone
      to compaction and blockage. In order to resolve these problems, iron powder
      coated with different polymer was tested in the treatment of chromium-polluted
      groundwater. Experimental results demonstrated that sodium alginate (SA) was the
      best package materials. According to analysis with FEI and EDX, pore structures
      were created by cross-linking of SA with Ca2+, in which a lot of attaching points
      exist, and through which Cr(VI) could react with interior iron powder. SA coating
      cast iron (SAC) and reduced iron (SAR) were tested in the treatment of chromium
      polluted groundwater individually; the results showed that the removal efficiency
      of Cr( VI) by SAC was double that by SAR. After optimization of technology
      parameters of SAC, the Cr(VI) removal process follows the pseudo first-order
      kinetics. Based on dynamic experiments with SAC, Cr(VI)/Fe(0) was up to 32.25 mg
      x g(-1) and the PRB maintained high permeability coefficient (2.38 cm x s(-1))
      after complete reaction. Compared with cast iron media is feasible in the
      remediation of chromium contaminated groundwater.

PMID- 24028004
TI  - [Removal of calcium and high-strength ammonia nitrogen from the wastewater of
      rare-earth elements hydrometallurgical process by chemical precipitation].
AB  - A lot of high-strength ammonia nitrogen wastewater is generated in the ion-type
      rare-earth elements hydrometallurgical process. Magnesium ammonium phosphate
      (MAP) precipitation was chosen to remove the ammonia nitrogen from the wastewater
      after Ca2+ was eliminated using Na2CO3 to generate CaCO3 precipitate, because the
      wastewater contained a lot of Ca2+, and Ca2+ was an important impact factor for
      MAP precipitation. Central composite design (CCD) is a principal response surface
      methodology (RSM) used in experimental design. Response surface methodology (RSM)
      was used to optimize the factors in MAP precipitation, achieving the optimal
      conditions and the precipitates under such conditions. Two kinds of precipitates
      were analyzed by scanning electron microscope (SEM) and X-ray diffraction (XRD).
      The results showed that when n (Ca2+): n (CO3(2-) = 1:1.05, mix rate and reaction
      time were 1500 r x min(-1) and 30 min, respectively, the removal ratio of Ca2+
      reached 100%; the optimal condition of MAP precipitation was pH = 9.03, n (Mg): n
      (N) = 1.20, n (P) : n (N) = 1.1, with a reaction time of 30 min and a mix rate of
      1000 r x min(-1), the removal ratio of ammonia nitrogen reached 95.40% and the
      residual total phosphorus concentration was 5.65 mg x L(-1). SEM and XRD analysis
      showed that the two kinds of precipitates were pure CaCO3 and MgNH4PO4 x 6H2O,
      respectively.

PMID- 24028005
TI  - [Leaching kinetics of josephinite tailings with sulfuric acid].
AB  - Leaching is the most important step of josephinite tailing recycle technology.
      This step can separate the valuable metal Mg from Si and other impure metal.
      Effects of sulfuric acid on leaching Mg efficiency from josephinite tailings were
      investigated. To obtain the leaching behavior, a modified unreacted shrinking
      core model that based on the experimental data was used to determine the
      dissolution kinetic parameters. The model was significant and showed that the
      dissolution of Mg2+ in josephinite tailing was controlled by the produce layer
      diffusion, apparent activation reaction energy E = 34.04 kJ x mol(-1). The
      produce layers obstruct the forward reaction of the dissolution of Mg2+.

PMID- 24028006
TI  - [Effects of HRT on fate of typical polycyclic musk by A2O process].
AB  - Fate of galaxolide (HHCB) and tonalide (AHTN) during the A2O process was
      investigated under different hydraulic retention time (HRT). Solid phase
      extraction (SPE) and gas chromatography mass spectrometry (GC/MS) were applied to
      determine the concentrations of the targets in the aqueous phase and sewage
      sludge. The results showed that HRT has an influence on the proportions of
      biodegradation and the discharge of excess sludge for HHCB by the A2O process,
      and it also affected the discharge of excess sludge for AHTN. With the extension
      of HRT, removal rates and removal contribution rates of HHCB and AHTN decreased
      in the anaerobic tank, while increased in the anoxic tank and aerobic tank. The
      final removal rates of the targets in the four operating conditions (6 h, 8 h, 10
      h and 12 h) were 73.93%, 73.05%, 75.14%, 76% and 48.76%, 44.27%, 57.17%, 62.9%,
      respectively. The removal efficiency was good for HHCB, but the removal
      efficiency of AHTN was poor by the A2O process. Meanwhile, with the extension of
      HRT, the removal efficiency showed no significant effect on HHCB, but it promoted
      the removal efficiency of AHTN.

PMID- 24028007
TI  - [Kinetic simulation of enhanced biological phosphorus removal with fermentation
      broth as carbon source].
AB  - As a high-quality carbon source, fermentation broth could promote the phosphorus
      removal efficiency in enhanced biological phosphorus removal (EBPR). The
      transformation of substrates in EBPR fed with fermentation broth was well
      simulated using the modified activated sludge model No. 2 (ASM2) based on the
      carbon source metabolism. When fermentation broth was used as the sole carbon
      source, it was found that heterotrophic bacteria acted as a promoter rather than
      a competitor to the phosphorus accumulating organisms (PAO). When fermentation
      broth was used as a supplementary carbon source of real municipal wastewater, the
      wastewater composition was optimized for PAO growth; and the PAO concentration,
      which was increased by 3.3 times compared to that in EBPR fed with solely real
      municipal wastewater, accounting for about 40% of the total biomass in the
      reactor.

PMID- 24028008
TI  - [Effluent carbon source improvement and sludge reduction by hydrolysis reactor
      with enhanced sludge utilization].
AB  - In order to strengthen the sludge hydrolysis and improve effluent carbon source,
      the structure of currently existing hydrolysis reactor was reformed. The new
      process combined separation of suspended solids in influent and hydrolysis of
      settled sludge. Experimental results show that the removal rate of SS was 81.4%,
      the average SS/BOD5 ratio of effluent was dropped to 0.4, far less than that of
      the influent ratios; SCOD/COD and COD(0.45-5)/COD ratio of the effluent increased
      by 35.4% and 17.7%, but the COD(> 100)/COD ratio reduced by 53.2%; BOD5/TN ratio
      increased from 3.7 to 4.7 and the BOD5/TP ratio from 23.8 to 36.4. The
      improvement of effluent carbon source was helpful for nitrogen and phosphorus
      removal in follow-up process. Meanwhile, the hydrolytic rate of sludge was up to
      51.9%, realizing the reduction and resource-regeneration.

PMID- 24028009
TI  - [Optimization of extracellular polymeric substance extraction method and its role
      in the dewaterability of sludge].
AB  - Seven commonly adopted extraction schemes were selected to extract extracellular
      polymeric substance (EPS) from the sludge, and the dewaterability of sludge was
      also investigated before and after extracting EPS. Results showed that
      Formaldehyde + NaOH and 2% EDTA methods were proved to be effective in extracting
      EPS from the sludge, and the total EPS production of the total suspend solid was
      128.86 mg x g(-1) and 42.38 mg x g(-1), respectively. However, the cell
      destructed seriously after extracted by Formaldehyde + NaOH and 2% EDTA methods.
      Heating method was a gentle and efficient method, and the total EPS production
      was 21.97 mg x g(-1). Sludge dewaterability was largely improved after extracted
      slime, loosely bound EPS and tightly bound EPS from the sludge flocs. It was also
      found that the higher content of EPS in slime, the worse dewaterability of
      sludge, and sludge dewaterability would be deteriorated when EPS was released
      from other layers to slime. Capillary suction time (CST) values of sludge from
      the ShekWuHui and Stonecutters Island Treatment works were 132.9 s and 229.9 s
      compared to 80.8 s and 79.4 s, separately after extracted Slime from sludge
      flocs, and the dewaterability of sludge was greatly improved.

PMID- 24028010
TI  - [Effectiveness of arsenite adsorption by ferric and alum water treatment
      residuals with different grain sizes].
AB  - Effectiveness of arsenite adsorption by ferric and alum water treatment residuals
      (FARs) with different grain sizes was studied. The results indicated that the
      content of active Fe and Al, the specific surface area and pore volume in FARs
      with different grain sizes were in the range of 523.72-1 861.72 mmol x kg(-1),
      28.15-265.59 m2 x g(-1) and 0.03-0.09 cm3 x g(-1), respectively. The contents of
      organic matter, fulvic acid, humic acid and humin were in the range of 46.97
      91.58 mg x kg(-1), 0.02-32.27 mg x kg(-1), 22.27-34.09 mg x kg(-1) and 10.76
      34.22 mg x kg(-1), respectively. Results of SEM and XRD analysis further
      demonstrated that FARs with different grain sizes were amorphousness. Batch
      experiments suggested that both the pseudo-first-order and pseudo-second-order
      equations could well describe the kinetics adsorption processes of arsenite by
      FARs. Moreover, the contents of arsenite absorbed by FARs increased with the
      increase of arsenite concentrations. The theoretical saturated adsorption
      capacities calculated from Langmuir isotherm model were in the range of 6.72
      21.79 mg x g(-1). Interestingly, pH showed little effect on the arsenite
      adsorption capability of FARs. The capability of FARs had a close relationship
      with their physicochemical properties. Correlation analysis showed that the
      active Fe and Al contents and pore volume had major effects on the arsenite
      adsorption capability of FARs.

PMID- 24028011
TI  - [Regional differences and development tendency of livestock manure pollution in
      China].
AB  - The rapid development of livestock production in China has brought livestock
      manure pollution as a serious environment problem, even threatens China's
      agriculture sustainable development. On the basis of public statistical data and
      field research data, this paper analyzed the magnitude of livestock manure
      excretion and pollution of China and different provinces in 2010, and predicted
      development tendencies of livestock manure excretion and pollution in 2020
      through the Decision Support System for China's Agricultural Sustainable
      Development (CHINAGRO). The result shows that total livestock manure excretion of
      China in 2010 is 1 900 million tons, and livestock manure pollution is 227
      million tons, while per hectare arable land of livestock manure pollution is 1.86
      tons. Provinces in the southeast China, such as Guangdong and Fujian, are areas
      with high pressure of livestock manure pollution. Model simulation shows that
      China's total amount of livestock manure pollution will increase to 298 million
      tons in 2020 without government intervention. The pressure of livestock manure
      pollution will become higher in most regions of China, especially in east and
      south regions. The situation in central and western region is better than that in
      east regions although the pollution pressure will also increase in those areas.
      Policy intervention such as taxes and subsidies should be adopted to reduce the
      discharge of livestock manure pollution, and encourage livestock production
      transfer from eastern areas to the central and western regions.

PMID- 24028012
TI  - [Quantitative partitioning of soil selenium in the selenium-rich area of Northern
      Zhejiang Plain].
AB  - To clarify the contribution of different component of selenium is the basis for
      evaluation of the sustainable development and utilization of selenium-rich soil.
      Xiuzhou district, where the soil is rich in selenium, was chosen as the study
      area, and its soil selenium content was qualitatively separated as the natural
      background component and the exogenous component through cross-validation of
      integrated geo-analysis and multivariate statistics. Subsequently, the
      contribution rate of the different component of the selenium content was
      separated quantitatively using frequency distribution functions. The results
      showed that the natural background component accounted for 90% in the soil
      selenium content and the exogenous component accounted for 10%, which indicated
      that the land sources rich in selenium in Xiuzhou district has the potential for
      sustainable development and utilization.

PMID- 24028013
TI  - [Effects of land use on manganese distribution and fractions in wetland soil of
      Sanjiang Plain, Northeast China].
AB  - A detailed investigation was conducted to study the variations of manganese
      contents and fractions in soil under different land use patterns in Sanjiang
      Plain, Northeast China. The purpose of this work was to study the changes of
      manganese and its fractions during wetland cultivation and their relationships
      with environment factors. The results indicated that the total manganese contents
      (Mn(tot)) were relatively low in wetland soils. When wetland was cultivated into
      dry farmland (corn field), M(tot) showed an increasing trend, and when wetland
      was cultivated into rice paddy, Mn(tot) manifested a decreasing trend. Among the
      four fractions of manganese in soil, the residual part (Mn(res)) and the
      reducible part (Mn(red)) were predominant while the acid extractable part
      (Mn(ext)) and the oxidizable part (Mn(oxi)) were secondary. During the
      cultivation of wetlands to corn field or rice paddy, Mn(oxi) was the only part
      with significant change. Mn(tot) and the transformations among manganese
      fractions were affected by many environmental factors, with sulfur content, pH
      and dissolved organic carbon playing leading roles.

PMID- 24028014
TI  - [Research on vertical distribution pattern and reserve of organic carbon in paddy
      field soil of Qianguo, Jilin].
AB  - Taking Qianguo paddy field of Jilin Province as investigation object, based on
      the soil test data of 7 different periods developed for 4 to 55 years, the
      vertical distribution of SOC content in the 1 m paddy field section was studied
      adopting the space scale method instead of time scale. The paddy soil carbon sink
      in last 20 years was discussed and the organic carbon storage of Qianguo paddy
      field soil was estimated. According to the second soil census data, the
      characteristics of soil SOC used in fields of different type were comparatively
      analyzed. The results showed that the paddy field SOC decreased from top to
      bottom by layer, which showed an increasing trend with the increase of
      development age; the organic carbon content in the surface soil layer (0-30 cm)
      (1 820.79 t) was 46.87% of the total organic carbon storage in deep soil (3
      885.05 t), and the soil SOCD content was highly different depending on the type
      of field, ranked in descending order as paddy field, dry land, and saline field.
      The development of paddy field is a SOC accumulating carbon sink process, which
      is conducive to the transfer of organic carbon from the surface soil layer to the
      bottom soil layer.

PMID- 24028015
TI  - [Soil organic carbon sequestration rate and its influencing factors in farmland
      of Guanzhong Plain: a case study in Wugong County, Shannxi Province].
AB  - Take Wugong County as an example, soil carbon storage and soil carbon
      sequestration rate were calculated, the change law of farmland soil organic
      carbon was explored, and the relationship of farmland soil organic carbon and
      natural factors, human factors was further revealed. The results of the study
      showed that: (1) The soil organic carbon contents in 80% of the sampling sites
      were in the range of 8.0-12.0 g x kg(-1), and the organic carbon contents in 0-20
      cm soils showed a normal distribution. (2) In 2011, the organic carbon density of
      the 0-20 cm farmland soil was 26.3 t x hm(-2), below the national average soil
      organic carbon density (33.45 t x hm(-2)) of the arable layer. In the last 30
      years, the soil carbon sequestration rate in the 0-20 cm layer was 71.3 kg x (hm2
      x a)(-1), and in the past five years, the carbon sequestration rate was 480 kg x
      (hm x a)(-1). The recent carbon sequestration rate was higher than the national
      average soil carbon sequestration rate of the arable layer [380.78 kg x (hm2 x
      a)(-1)]. (3) In the semi-humid plain region, soil organic carbon was mainly
      affected by soil types, landform types, organic fertilizer. Soil types accounted
      for 30.2% of the organic carbon variability; the landform types and the organic
      fertilizer could explain 37.7% and 32.1%, respectively. The results of the
      comprehensive analysis showed that the farmland soil organic carbon density of
      Wugong County in the past 30 years is increasing, and this probably relies on the
      utilization of chemical fertilizer and the returning straw. Further study should
      be conducted on the impact of the chemical fertilizer and returning straw.

PMID- 24028016
TI  - [Effects of biological regulated measures on active organic carbon and erosion
      resistance in the Three Gorges Reservoir region soil].
AB  - To gain a better knowledge of characteristics of soils and provide a scientific
      basis for soil erosion control in the Three Gorges Reservoir Area, contents of
      aggregates and total soil organic carbon (SOC), as well as soil active organic
      carbon fractions including particulate organic carbon (POC), readily oxidized
      organic carbon (ROC), dissolved organic carbon (DOC), microbial biomass carbon
      (MBC) in the 0-30 cm soil layer under seven different biological regulated
      measures were studied by the field investigation combined with the laboratory
      analysis. Results showed that the content of the SOC and active organic carbon
      fractions decreased with the increasing soil depth; the content of the SOC and
      active organic carbon fractions in 0-10 cm was significantly higher than that in
      20-30 cm. The stability of soil aggregates were also significantly influenced by
      biological regulated measures, the content of > 0.25 mm water-stable aggregates
      in seven types of biological regulated measures was in the order of Koelreuteria
      bipinnata + Cassia suffruticasa > hedgerows > closed forest > natural restoration
      > economic forest > traditional planting > control plot, moreover, the content of
      0.25 mm water-stable aggregates correlated positively with the content of SOC.
      Soils under different biological regulated measures all demonstrated fractal
      features, and soil under the measure of Koelreuteria bipinnata + Cassia
      suffruticasa was found to have the lowest value of fractal dimension and soil
      erodiable K, indicating a relatively strong structure stability and erosion
      resistant capacity. Negative correlation was observed when compared the content
      of active organic carbon fractions with the soil erodiable K. It can be concluded
      that properties of soil can be managed through biological regulated measures;
      thence had an influence on the soil erosion-resistant capacity.

PMID- 24028017
TI  - [Quantifying soil autotrophic microbes-assimilated carbon input into soil organic
      carbon pools following continuous 14C labeling].
AB  - Soil autotrophic microbe has been found numerous and widespread. However, roles
      of microbial autotrophic processes and the mechanisms of that in the soil carbon
      sequestration remain poorly understood. Here, we used soils incubated for 110
      days in a closed, continuously labeled 14C-CO2 atmosphere to measure the amount
      of labeled C incorporated into the microbial biomass. The allocation of 14C
      labeled assimilated carbon in variable soil C pools such as dissolved organic C
      (DOC) and microbial biomass C (MBC) were also examined over the 14C labeling
      span. The results showed that significant amounts of 14C-SOC were measured in
      paddy soils, which ranged from 69.06-133.81 mg x kg(-1), accounting for 0.58% to
      0.92% of the total soil organic carbon (SOC). The amounts of 14C in the dissolved
      organic C (14C-DOC) and in the microbial biomass C (14C-MBC) were dependent on
      the soils, ranged from 2.54 to 8.10 mg x kg(-1), 19.50 to 49.16 mg x kg(-1),
      respectively. There was a significantly positive linear relationship between
      concentrations of 14C-SOC and 14C-MBC (R2 = 0.957**, P < 0.01). The 14C-DOC and
      14C-MBC as proportions of total DOC, MBC, were 5.65%-24.91% and 4.23%-20.02%,
      respectively. Moreover, the distribution and transformation of microbes
      assimilated-derived C had a greater influence on the dynamics of DOC and MBC than
      that on the dynamics of SOC. These data provide new insights into the importance
      of microorganisms in the fixation of atmospheric CO2 and of the potentially
      significant contributions made by microbial autotrophy to terrestrial C cycling.

PMID- 24028018
TI  - [Analysis of soil respiration and influence factors in wheat farmland under
      conservation tillage in southwest hilly region].
AB  - In order to investigate the effect of conservation tillage on soil respiration in
      dry cropping farmland in southwest purple hilly region, the LI6400-09 respiratory
      chamber was adopted in the experiment conducted in the experimental field in
      Southwest University in Beibei, Chongqing. The respiration and the hydrothermal
      and biotic factors of soil were measured and analyzed during the growth period of
      wheat in the triple intercropping system of wheat/maize/soybean. There were four
      treatments including T (traditional tillage), R (ridge tillage), TS (traditional
      tillage + straw mulching) and RS (ridge tillage + straw mulching), which were all
      in triplicates. The results indicated that the soil respiration rate changed in
      the range of 1.100-2.508 micromol x (m2 x s)(-1) during the reproductive growth
      stage of wheat. There were significant differences in soil respiration rate among
      different treatments, which could be ranked as RS > R > TS > T. The soil
      temperature in the 10cm layer was ranked as T > R > TS > RS. The relationship
      between soil respiration and soil temperature fitted well with an exponential
      function, in which the Q10 values were 1.25, 1.20, 1.31 and 1.26, respectively.
      The soil moisture in the 5cm layer was ranked as TS > RS > T > R. The best
      fitting model between soil moisture and soil respiration was a parabolic curve,
      indicating the presence of soil moisture with the strongest soil respiration. The
      response threshold of wheat to soil moisture was 14.80%-17.47% during the
      reproductive stage. The dominant groups of soil animals were Collembola and
      Acarina, which were correlated with soil respiration to some extent. The
      correlation was high in the treatments T and R, ranged from 0.669-0.921, whereas
      there was no remarkable correlation in the other treatments.

PMID- 24028019
TI  - [Distribution characteristics and risk evaluation of organochlorine pesticides in
      soil from relocation areas of the Danjiangkou Reservoir].
AB  - Twenty-six surface soil samples collected in Danjiangkou Reservoir were analyzed
      for organochlorine pesticides (OCPs) residues by GC-MS. The distribution
      characteristics, compositions and origin of OCPs were discussed. Pollution level
      and potential ecological risks of OCPs were also evaluated. The results showed
      that the concentration rang of total OCPs in soil was nd-249.37 ng x g(-1) (with
      a mean of 24.82 ng x g(-1)). The recent occurrence levels in soil were nd-69.68
      ng x g(-1) for HCHs and nd-104.53 ng x g for DDTs. DDTs concentrations in soil
      were higher than those of HCHs. The OCPs residues in soil were mainly originated
      from the early residues, atmospheric deposition and recent input of OCPs
      components. The correlation between OCPs contents and organic matter contents in
      soil was not significant, indicating that the contents of OCPs in soil were also
      affected by other factors. Compared with other soil samples from different
      regions, the contents of OCPs in soil of relocation areas of the Danjiangkou
      Reservoir were at medium-low level. The study suggested that the OCPs in soil of
      relocation areas of the Danjiangkou Reservoir are in a state of low danger,
      whereas OCPs still display risks locally in some places.

PMID- 24028020
TI  - [Risk assessment and countermeasure of BTEX in pesticide factory].
AB  - BTEX are important environmental pollutants, harmful to human through respiratory
      inhalation, digestive tract and skin contact, and also have teratogenic,
      mutagenic and carcinogenic effects. BTEX were detected in multi-media to identify
      their distributions and assess their human health risk in a pesticide factory in
      Hebei province. Purge and trap GC-MS, adsorption/thermal desorption GC
      chromatography and the health risk assessment model were applied, and
      corresponding management measures were proposed. The results showed that BTEX
      existed in soil, dust, air, groundwater and wastewater. The concentration of BTEX
      in dust of the production area was 7.33 mg x kg(-1), in particular the
      concentration of toluene was 5.64 mg x kg(-1), exceeding the Canadian industrial
      land standard. Building three scenarios for working more than 10 years, 20 years
      and 30 years, the total non-carcinogens index was 4.19 x10(-3), 8.25 x 10(-3) and
      1.22 x 10(-2), respectively, all lower than 1; the carcinogens index of benzene
      was 1.70 x 10(-7), 3.34 x 10(-7) and 4.92 x 10(-7), respectively, all lower than
      10(-6). It indicated that there was no significant non-carcinogens and
      carcinogens hazard to workers inside the factory, but they might be exposed to
      more health risks if their work experience increase. Finally, recommendations for
      improving the environmental quality and personnel security in the factory were
      proposed based on the research results.

PMID- 24028021
TI  - [Accumulation of S, Fe and Cd in rhizosphere of rice and their uptake in rice
      with different water managements].
AB  - The interactions between the concentrations of sulfur, iron and cadmium in the
      rhizosphere and their uptakes in rice (Oryza sativa L. ) were studied using paddy
      soil which was contaminated by acid mine drainage under five water-management
      treatments of 60%, 80%, 100% field moisture capacity (FMC), flooded throughout
      the entire rice growth period and flooded followed by keeping 80% FMC after
      heading-flowering period. The water managements had no significant influence on
      the Fe and Cd concentrations in rhizosphere soil in maturity stage, although the
      concentration of Cd slightly increased with the increase of soil moisture in the
      tillering stage. However, the uptake of Fe and Cd in rice was obviously related
      to water managements. The increase of soil moisture enhanced the uptake of Fe,
      but decreased the uptake of Cd in different organs of rice (roots, stems and
      leaves, grains) except for Cd uptake of the root in the 60% FMC treatment.
      However, aerobic treatment after heading-flowering period enhanced Cd uptake in
      rice in all treatments, but did not influence the uptake of Fe in rice. On the
      other hand, the increase of soil moisture reduced the concentrations of total
      sulfur and available sulfur in the rhizosphere soil except for the 60% FMC
      treatment, which corresponded with the reduction of Cd uptake in rice. And the
      aerobic treatment promoted Cd uptake in rice, which was also positively related
      to the increase of total sulfur and available sulfur in rhizosphere soil.
      Therefore, it was concluded that the uptake and speciation of sulfur in
      rhizosphere soil other than the change of Fe concentration induced by water
      management could play an important role in Cd uptake of rice.

PMID- 24028022
TI  - [Effects of nitrate on organic removal and microbial community structure in the
      sediments].
AB  - The strategy promoted pollutant degradation and transformation under the
      anaerobic circumstance by adding nitrate as an electron acceptor has been widely
      used in sediment bioremediation. However, few literature reports on organic
      removal characteristics and microbial community responses in the contaminated
      river sediment under the nitrate reduction condition. Methods including the polar
      and non-polar chemical fractionation, relative abundance detection of organic
      matters by GC-MS were combined and applied to investigate organic removals and
      PCR-DGGE analysis was used for microbial community structures in sediment
      incubation systems with or without calcium nitrate addition. The results
      indicated that the addition of calcium nitrate could significantly enhance
      removal efficiencies of organic pollutants. The removal efficiency of total
      organic carbon (TOC) and the total peak area of organic matters in GC-MS were
      47.25% and 29.55% which were higher than those of the control. The effect
      descending order of organic pollutants was: silicon materials > alkanes >
      polycyclic aromatic hydrocarbons > heterocyclic compounds > olefins > benzene
      homologues > polar compounds > phthalates > aldehydes and ketones > alkyl esters.
      And removal rates of silicon materials, the persistent organic pollutants,
      benzene homologues and heterocyclic compounds were 46.73%, 36.25%, 23.19% and
      35.92% which were higher than those of the control. The PCR-DGGE profile of
      bacterial 16S rDNA V3 fragments showed obviously different microbial community
      structures between the treatment and the control systems. Blastn analysis
      revealed that sequences of 10 predominant bands from DGGE profile were closely
      related to Proteobacteria, Actinobacteria, Clostridia, Chloroflexi, Caldiserica
      and uncultured bacterium. The research findings provide some helpful scientific
      information for promoting organic pollutant removal of river sediment by nitrate
      reduction.

PMID- 24028023
TI  - [Zero-valent iron-enhanced azoreduction by the Shewanella decolorationis S12].
AB  - Characteristics and optimal reaction conditions of anaerobic azoreduction by the
      Shewanella decolorationis S12 in the presence of zero-valent iron (ZVI) were
      evaluated in this study. The results showed that the presence of ZVI
      significantly enhanced the decolorization rate of azo dye. In the presence of 20
      mmol x L(-1) ZVI, the decolorization rate of 1 mmol x L(-1) amaranth reached up
      to 100% by the Shewanella decolorationis S12 after 30 h incubation, which was
      significantly higher than 23.16% and 94.66% in the pure strain S12 and pure ZVI
      treatment systems, respectively. When 20 mmol x L(-1) of sodium formate was added
      in the medium, ZVI still improved the decolorization rate of amaranth by 20.54%.
      In addition, the presence of ZVI significantly increased the azo dye treatment
      amount in the ZVI plus S12 system. In the system with ZVI, 1 mmol x L(-1)
      amaranth was completely reduced 11 times in fed-batch process within 276 h, while
      the dye could only be completely reduced 3 times in the system without ZVI. The
      optimal pH and the Fe(0) dose for the ZVI plus S12 system was 9.0 and 60 mmol c
      L(-1), respectively. The microscale ZVI was more suitable for the decolorization
      than those with larger size and the nanoscale ZVI. This study may provide some
      useful information for improving the biodegradation of azo dye in the treatment
      system with ZVI.

PMID- 24028024
TI  - [Isolation, identification of two aerobic denitrifiers and bioaugmentation for
      enhancing denitrificaition of biofilm under oligotrophic conditions].
AB  - Two aerobic denitrifying bacteria were isolated from the sludge of municipal
      wastewater treatment plant by enrichment, preliminary screening with BTB culture
      medium and the denitrification potential test and identified through 16S rDNA
      sequence analysis. Then they were bioaugmented to oligotrophic biofilm system
      respectively, aiming to enhance the denitrification capacity. The two strains
      were identified as Pseudomonas aeruginosa and Pseudomonas putida respectively.
      They could remove 78% or 82% of the total nitrogen in the simulate wastewater
      when existed alone. And the total nitrogen removal efficiency of the biofilm
      system reached 68% and 64% after bioaugmentation with two trains, increased by
      47% and 43% compared to the control, respectively. Meanwhile, the ammonia
      nitrogen was nearly 100% removed. It can be concluded that two aerobic
      denitrifiers can enhance the denitrification of biofilm system significantly
      under oligotrophic conditions and will not inhibit the nitrification process,
      therefore can help biofilm system achieve simultaneous nitrification and
      denitrification.

PMID- 24028025
TI  - [Rapid enrichment and cultivation of denitrifying phosphate-removal bacteria and
      its identification by fluorescence in situ hybridization technology].
AB  - The present work focused on a rapid enrichment and cultivation of denitrifying
      phosphate-removal bacteria (DPB) in a membrane bio-reactor(MBR) by using A2/O
      anaerobic sludge from a wastewater treatment plant as seed, as well as providing
      an identification method. In the experiments, sodium acetate was used as the
      carbon source and a certain amount of nitrate was added to the MBR in the anoxic
      stage. Results showed that, with the efficient trap of the hollow-fiber membrane
      module, the proportion of DPB in all the phosphate-accumulating organisms (PAOs)
      increased from 24% to 93% within 35 days after two-stage's cultivation including
      anaerobic/aerobic and anaerobic/anoxic, during which the removal efficiency of
      nitrogen and phosphorus reached more than 90%. The activated sludge was
      identified by combining a regular method and the fluorescence in situ
      hybridization (FISH) technique, which demonstrated that Pseudomonas sp. and
      Rhodocyclus sp. were the dominant bacteria in the used bioreactor.

PMID- 24028026
TI  - [Identification of a denitrifying polyphosphate-accumulating organism (DPAO) and
      study on its denitrifying functional genes].
AB  - A denitrifying polyphosphate-accumulating organism (DPAO) was isolated and
      identified, and the denitrifying functional genes were investigated. The strain
      ZQN2 was isolated using denitrifying medium. It was distinguished as DPAO by
      tests of aerobic phosphorus uptake, nitrate reduction, metachromatic granules and
      PHB (poly-beta-hydroxybutyrate) granules dyeing. Test of anaerobic phosphorus
      release/anoxic phosphorus uptake showed that strain ZQN2 released phosphorus and
      synthesized PHB at the anaerobic phase and used NO3- as acceptor to oxidize PHB
      during the anoxic phase with luxury phosphorus uptake, performing the function of
      simultaneous denitrifying phosphorus removal. The 16S rRNA gene sequence of
      strain ZQN2 was used for homology analysis and construction of phylogenetic
      trees. The results suggested that the 16S rRNA gene sequence of ZQN2 had up to
      99% homology with those of many strains of Bacillus cereus strains in GenBank
      database. With physiological and biochemical reactions, the strain ZQN2 was
      identified as Bacillus cereus. The result of denitrifying functional gene study
      suggested that strain ZQN2 was the type of nirS+ and nirK-, which confirmed its
      denitrifying function from molecular biology point of view. Moreover, the
      phylogenetic analysis of nirS gene of ZQN2 showed that it was closely related to
      many strains of Pseadomonas aeruginosa, which was different from the analysis
      results of the 16S rRNA.

PMID- 24028027
TI  - [Isolation and characterization of a highly efficient BBP-degrading bacterium].
AB  - A bacterial strain HS-B1 which can utilize n-butyl benzyl phthalate as the sole
      source of carbon and energy was isolated from contaminated sludge in the Jinsha
      River of Hubei Province. Based on its morphology, physiological characteristic
      and 16S rDNA sequence analysis, HS-B1 was identified as Acinetobacter sp.. Shake
      flask experiments indicated the optimum pH, temperature for growth and BBP
      biodegradation by HS-B1 was found to be 8.0 and 35 degrees C, respectively. When
      using 0.10 mmol x L(-1) non-ionic surfactant Tween-80 as co-solvent to increase
      the apparent solubility of BBP in water, HS-B1 was able to completely degrade 1
      000 mg x L(-1) BBP within 48 hours. Diversity of degradable substrates also
      showed that HS-B1 can efficiently utilize many other phthalate esters such as
      dimethyl phthalate and diethyl phthalate. It revealed that the strain HS-B1 has
      special application potential in dealing with the pollution caused by phthalate
      esters.

PMID- 24028028
TI  - [Degradation of nicosulfuron by combination effects of microorganisms and
      chemical hydrolysis].
AB  - A strain which was capable of degrading nicosulfuron in the presence of glucose
      was isolated from nicosulfuron contaminated wetland soil, and it was identified
      as Klebsiella sp. based on 16S rDNA gene sequencing analysis. The strain could
      grow using nicosulfuron as the sole nitrogen source. The optimal temperature was
      35 degrees C and the initial pH was neutral to weak acid. Hydrolysis experiments
      indicated that nicosulfuron remained stably under neutral and alkaline
      conditions, while in acidic conditions, it hydrolyzed quickly. Based on
      biodegradation experiments, when the concentration of glucose in culture was 5 g
      x L(-1), the strain could degrade 99.4% of nicosulfuron after incubation for 10
      days at 35 degrees C, initial pH = 7; pH of the solution decreased from initial
      7.0 to 4.0 in the meantime. When the concentration of glucose in culture solution
      was decreased to 500 mg x L(-1) and 100 mg x L(-1), with other conditions
      unchanged, only 11.7% and 6.6% of nicosulfuron were degraded, respectively, and
      pH of the solution remained at around 7.0. It was proposed that the degradation
      of nicosulfuron was caused by hydrolysis under acidic conditions at low pH which
      was resulted from the biodegradation of glucose by the strain. Therefore, the
      removal of nicosulfuron was actually caused by combined effects of microorganisms
      and chemical hydrolysis.

PMID- 24028029
TI  - [Isolation, screening and identification of prometryne-degrading bacteria and
      their degrading characteristics].
AB  - The purpose of this study was to develop some bacterial strains that could
      degrade prometryne effectively. Bacteria were screened and purified from
      sediments of a pesticide plant with the method of domestication with gradient
      concentrations. Two strains were isolated and named P-1 and P-2, respectively.
      According to their morphology, physiological, biochemical properties and the
      analysis of their 16S rRNA gene sequences, the strain P-1 is Gram negative and
      identified as Ochrobactrum; the strain P-2 is Gram positive and identified as
      Bacillus. GenBank Accession numbers are HM004554 and HM004555, respectively.
      Degradation rates of the strains P-1 and P-2 for prometryne concentration with 40
      mg x L(-1) were 46.5% and 65.4% after 12 days in the liquid culture experiment,
      respectively. This study provides an essential material and theoretical
      foundation for the remediation of prometryne contaminated soils.

PMID- 24028030
TI  - [Preparation of PVA-SA-PHB-AC composite carrier and m-cresol biodegradation by
      immobilized Lysinibacillus cresolivorans].
AB  - Due to the effects of outer environment and concentration limit on the
      biodegradation of m-cresol, a carrier with adsorption ability was synthesized. A
      PVA-SA-PHB-AC composite membrane was prepared by adding SA, PHB and AC into PVA
      immobilization carrier using the combination of freezing-thawing and boric acid
      methods. A highly-effective m-cresol-degrading strain Lysinibacillus
      cresolivorans was entrapped in it and the effects of structural properties such
      as micro-structure, stability and diffusion coefficient on m-cresol
      biodegradation were investigated. The results showed that PVA-SA-PHB-AC composite
      membrane had uniform pore opening, of which the average pore size, specific
      surface area, m-cresol adsorption capacity and diffusion coefficient was 33.68
      nm, 15.30 m2 x g(-1), 3.86 mg x g(-1) and 5.62 x 10(-8) m2 x min(-1),
      respectively. It could be reused for more than two months, m-Cresol removal by
      immobilized L. cresolivorans was the coupling of adsorption and biodegradation,
      and the removal rate was jointly determined by mass-transfer rate and
      biodegradation rate. When the initial concentration of m-cresol was lower than
      350 mg x L(-1), the mass-transfer rate of PVA-SA-PHB-AC was smaller than the
      biodegradation rate. The m-cresol removal rate depended on the mass-transfer
      rate, when the concentration was higher than 380 mg x L(-1), it was determined by
      the biodegradation rate. The addition of adsorbent could decrease the mass
      transfer coefficient in the carrier, while the higher concentration of substrate
      could be tolerated and the efficient biodegradation could be achieved in a wider
      range of concentrations. The biodegradation of m-cresol by immobilized
      microorganism showed that the modified carrier increased the reaction kinetics in
      a range of initial concentrations.

PMID- 24028031
TI  - [Extraction of surface active substance and analysis of demulsifying
      characteristics for the demulsifying strain Alcaligenes sp. S-XJ-1].
AB  - Extraction and identification of surface active substance of Alcaligenes sp. S-XJ
      1, as well as description of its emulsion breaking process were conducted to
      reveal the demulsifying characteristics of this demulsifying strain. Alkali
      solvent was adopted in the extraction process with conditions optimized as 35
      degrees C, 0.08 mol x L(-1) of alkali concentration, 12 g x L(-1) of sample to
      solution ratio, and 4 h of extraction time by launching both single-factor and
      orthogonal tests. Under this optimal condition, the extracted surface active
      substance (the extraction ratio was 36.1%) achieved 77% emulsion breaking ratio
      for 500 mg x L(-1) within 48 h. FT-IR showed the existence of glycolipids, lipids
      and proteins in the surface active substance, the molecular weight of which
      mainly scattered between 55 and 61 256. Saccharides, lipids and proteins were
      identified as the three chief components in surface active substance with the
      content of 22.2%, 7.5% and 13.4%, respectively. The proteins were further proved
      to take the most responsibility for the emulsion breaking ability. Moreover,
      obvious difference in the emulsion breaking process was demonstrated between the
      original demulsifying strain S-XJ-1 and the extracted surface active substance by
      real time observation of Turbiscan Lab Expert. The results suggested that the
      demulsifying efficiency of the strain was jointly contributed by its surface
      active substance and demulsifying cell morphology, and the former possessed
      higher functional priority than the latter.

PMID- 24028032
TI  - [Diversity of culturable filamentous bacteria in the activated sludge from A2O
      wastewater treatment process].
AB  - The anoxic-anaerobic-oxic (A2O) process is widely used in wastewater treatment
      plant, however, sludge bulking and foaming are the most frequent operational
      problems in this process. Activated sludge bulking is caused by the overgrowth of
      some types of filamentous bacteria, especially Microthrix parvicella. In the
      study, 17 strains of filamentous bacteria were isolated from the bulking sludge
      of A2O process using Gause's medium. The 16S rRNA genes of the 17 isolates were
      sequenced to analyze their diversity. The results showed all of the 17 isolates
      were Streptomyces. Further analysis of these strains by the repetitive sequence
      based on polymerase chain reaction (rep-PCR) technology showed that there was a
      high diversity in these isolated Streptomyces. The physiological properties of
      them were different from Microthrix parvicella. The settleability of activated
      sludge was improved when some of the isolates were inoculated.

PMID- 24028033
TI  - [Composition and transformation of leachates during municipal solid waste
      composting].
AB  - The composition and evolution characteristics of inorganic anions, ammonia, heavy
      metals and organic compounds in leachates with different composing times were
      studied in a composting plant in order to clarify its composition and evolution
      and search for a suitable processing technology. The results showed that
      concentrations of EC, F-, Cl-, SO4(2-) and NH4(+) -N decreased during the
      composting process, while the contents of NO2(-) -N, NO3(-) -N and Org-N were
      related to the oxidation reduction atmosphere of leachates. The Pb, Cd, Cu, Zn
      and As concentrations in leachates exhibited a decrease trend during the
      composting process, while contents of heavy metals Cr, Ni, Fe, Mn showed an
      increase trend with increasing composting time. The composting leachate organics
      comprised mainly of protein-like substance, but also consisted of humic-like
      substances. The leachate organics were suitable to be treated by biochemical
      process firstly, and then by physico-chemical technique. The relative content of
      protein-like substances firstly increased and then decreased, while that of humic
      like matter exhibited an opposite trend. The contents of salinity and heavy metal
      in compost leachates were high, which caused the improper reflux utilization of
      leachates. The compost leachates should be treated by the combined biochemical
      and physico-chemical process before emission.

PMID- 24028034
TI  - Thinking about evidence.

PMID- 24028035
TI  - Factors influencing job satisfaction of oncology nurses over time.
AB  - In this study, we tested a structural equation model to examine work environment
      factors related to changes in job satisfaction of oncology nurses between 2004
      and 2006. Relational leadership and good physician/nurse relationships
      consistently influenced perceptions of enough RNs to provide quality care, and
      freedom to make patient care decisions, which, in turn, directly influenced
      nurses' job satisfaction over time. Supervisor support in resolving conflict and
      the ability to influence patient care outcomes were significant influences on job
      satisfaction in 2004, whereas, in 2006, a clear philosophy of nursing had a
      greater significant influence. Several factors that influence job satisfaction of
      oncology nurses in Canada have changed over time, which may reflect changes in
      work environments and work life. These findings suggest opportunities to modify
      work conditions that could improve nurses' job satisfaction and work life.

PMID- 24028036
TI  - Challenges having conversations about sexuality in ambulatory settings: part II-
      health care provider perspectives.
AB  - Cancer treatment can have a significant impact on an individual's quality of
      life. In particular, body image and sexuality can be compromised. There is
      increasing evidence that conversations about these specific consequences are not
      happening often between cancer patients and health care providers, especially in
      busy ambulatory settings. This study was undertaken to explore the perspectives
      of cancer care providers regarding the conversations about sexuality that happen
      following a cancer diagnosis. There was a desire to understand more about the
      barriers that exist with regards to having this conversation in daily practice.
      Thirty-four cancer care professionals (nurses, physicians, social workers and
      radiation therapists) were interviewed to explore their experiences in having
      conversations about sexuality. Transcripts were subjected to a standard
      qualitative content and theme analysis. Six themes emerged from the analysis.
      Overall, participants acknowledged treatment can have an impact on a patient's
      sexuality. For the most part, any conversations about sexuality topics occurred
      during informed consent processes before treatment began or when a patient raised
      a question about a side effect. However, these conversations rarely covered more
      than the physical side effects and did not focus on the impact of those side
      effects on emotional and personal relationships or intimacy. Most providers
      waited for patients to raise any concerns and expressed their own personal
      discomfort and lack of training in holding these types of conversations. They
      perceived the conversations as difficult for themselves and for patients. The
      findings support the need to clarify role expectations for cancer nurses, as well
      as other members of the cancer care team, about patient care regarding sexuality,
      and the provision of education to support the expected role.

PMID- 24028038
TI  - It's not just hair: a Sikh perspective.

PMID- 24028037
TI  - Sex talk and cancer: who is asking.
AB  - Estimates of sexual health problems after cancer treatment range from 40% to 100%
      across cancers, with almost half of cancer survivors reporting problems with
      sexual functioning. While many side effects of cancer treatment gradually resolve
      within the first year or two, many sexual health issues do not. These problems
      can remain severe and constant and can even become worse over time causing
      considerable distress. Although sexual health issues are common, they are not
      addressed often enough in cancer settings. There are a variety of barriers to
      addressing sexual health concerns. In this lecture, we discuss those challenges
      and offer some possible approaches nurses could use to improve sexual health
      care, including the BATHE and the PLISSIT models. Case examples highlighting the
      models are included.

PMID- 24028039
TI  - How does a practicing oncology nurse promote high-quality cancer care?

PMID- 24028040
TI  - Lean mean patient care machine. Health care uses lean philosophy to improve
      patient experiences.

PMID- 24028041
TI  - Institution uses lean quality model to reduce chemotherapy errors and length of
      stay.

PMID- 24028042
TI  - A culture of quality. Oncology nurses focus on defining, measuring, and managing
      quality care.

PMID- 24028043
TI  - Initiative helps blow the steam off pressure ulcer rates.

PMID- 24028044
TI  - What are the general diet guidelines for patients after they have completed
      treatment?

PMID- 24028045
TI  - Quality care close to home. Quality really counts when caring for patients in
      underserved areas.

PMID- 24028046
TI  - ONS chapter supports quality patient education in Navajo Nation.

PMID- 24028047
TI  - Help rural HCT recipients overcome barriers to post-treatment care.

PMID- 24028048
TI  - The case of the toxic transplant tremors.

PMID- 24028049
TI  - Graduate nursing student receives oncology reference section by simply asking.

PMID- 24028050
TI  - What is the impact of nosocomial infections on the oncology population?

PMID- 24028051
TI  - New radiation therapy prolongs metastatic prostate cancer survival.

PMID- 24028052
TI  - Let's lead the future of oncology nursing together.

PMID- 24028053
TI  - [Bergey's Manual of Systematic Bacteriology (second edition) Volume 5 and the
      study of Actinomycetes systematic in China].
AB  - Bergey's Manual of Systematic Bacteriology (hereinafter referred to as "Bergey's
      Manual") is the collection of academic views accepted by taxonomists in many
      countries. It has scientificity, unitarity and practicality. "Bergey's Manual"
      (special issue of Actinomycetes) divided into two parts (part A and part B) was
      published in May, 2012. Under the guidance and the organization of Michael
      Goodfellow et al., the great work has been completed successfully in May 2012.
      "Bergey's Manual" made a great modification on the systematic of Actinomycetes
      and formally set up the phylum of Actinobacteria, which encompasses 6 classes, 23
      orders (include one order incertae sides), 53 families, 222 genera and about 3000
      species. The taxonomic catalogue is Bacteria, phylum of Actinobacteria, under the
      phylum there are class, order, family, genera and species. "Bergey's Manual"
      collected a great deal of new taxa, which were published in IJSEM (International
      Journal of Systematic and Evolutionary Microbiology) by Chinese scientists. We
      need to indicate that due to its too rigorous, conservative writing purpose and
      long publication periods, "Bergey's Manual" fails to collect new research results
      using the molecular approaches of multilocus sequence analysis "MLSA", gene chip
      technology and genome technologies, which however will profoundly change the
      taxonomy of prokaryotes in the near future.

PMID- 24028054
TI  - [Tolerance of Saccharomyces cerevisiae to monoterpenes--a review].
AB  - Tolerance of Saccharomyces cerevisiae to monoterpenes is important in both
      metabolic engineering of the yeast to produce these chemicals de novo and
      efficient use of biomass containing these chemicals. Understanding the mechanisms
      in the tolerance of S. cerevisiae to monoterpenes could facilitate the
      construction of yeast strains with enhanced monoterpenes resistance, and
      therefore improve related bioprocesses. Monoterpenes could disturb the redox
      balance in S. cerevisiae, therefore increase the accumulation of reactive oxygen
      species (ROS) and result in cell death. S. cerevisiae has to systematically
      improve its antioxidative ability to deal with the ROS induced damage. The
      current review summarized the recent developments in demonstration of the
      tolerance of S. cerevisiae to different typical monoterpenes mainly from the
      aspect of the antioxidative mechanisms. Based on the analysis of the previous
      works, further attempts to demonstrate the mechanisms were proposed.

PMID- 24028055
TI  - [Escherichia coli Nissle 1917 as safe vehicles for intestinal immune targeted
      therapy--a review].
AB  - It is difficult to stimulate efficient gut mucosal immune response to intestinal
      infection. This article critically reviews the research progressin Escherichia
      coli strain Nisslel917 ( EcN) actingas a safe vehicle for the intestinal mucosal
      immunity, to restore gastrointestinal disorder and relieve ulcerative colitis.
      EcN is an orally administered probiotics, combining the excellent colonization
      and non-immunogenic character, and can be an ideal live vector candidate. This
      strain could be a tumor-targeted delivery of TAT-Apoptin fusion gene to
      colorectal cancer. In the treatment of ulcerative colitis and Crohn's disease,
      the recombinant strain of EcN can be used as a target therapeutics for defensins
      presenting. Genetically modified EcN could be an ideal carrier organism for gut
      focused in situ synthesis and expression of specific localized antigen delivery
      into the intestine, and stimulate specific mucosal immune response. In vitro
      trial demonstrated that intestinal recombinant E. coli Nissle-HA110-120 has the
      potential to stimulate antigen specific response, but EcN itself does not induce
      mucosal immune response and influence peripheral tolerance to self-antigen. At
      the same time, there are evidences that EcN is safe. Recombinant E. coli Nissle
      HA110-120 does not migrate, clonally expand and activate specific CD4+ T cells,
      neither in healthy mice nor in other animals with acute colitis, even when the
      intestinal epithelium suffer from inflammation and the barrier function of the
      epithelial layer being destroyed.

PMID- 24028056
TI  - [Enhancement of human insulin precursor production by increasing the copy number
      in Pichia pastoris].
AB  - OBJECTIVE: The aim of this study was to further increase the yield of insulin
      precursor by Pichia pastoris. METHODS: For this, we transformed the expression
      vector pPICZalpha-IP into P. pastoris X-33 using electroporation and screened two
      mutant strains B4 and S6 on the YPD plate containing 100 microg/mL zeocin. Both
      could overexpress human insulin precursor. Taking B4 and S6 as start strains, we
      repeatedly transformed SacI linearizing pPICZalpha-IP into P. pastoris X-33 by
      electroporation, then screened a new mutant strain 2B4 (with 7 copies) on the
      1000 microg/mL zeocin YPD plate. RESULTS: After cultivation, the human insulin
      precursor yield of 2B4 strain was 2.7 fold higher than that of B7. Meanwhile, the
      cell growth was not inhibited. The target gene transcription level of 2B4 was 2
      fold higher than that of B7 by real-time quantification PCR. CONCLUSION: The
      strategy of combining resistance screening and repeated electroporation was
      efficient to increase the copy number of target gene, so as to facilitate higher
      transcription level and enhance objective recombinant protein yield.

PMID- 24028057
TI  - [Response of Nostoc flageliforme cell to Cu2+, Cr2+ and Pb2+ stress].
AB  - OBJECTIVE: This study aimed to investigate the effects of Cu2+, Cr2+ and Pb2+
      stress on Nostoc flagelliforme cell. METHODS: The response of Nostoc
      flagelliforme cell was analyzed under the stress. The modified BG11 culture
      medium containing different heavy metal ions of 0, 0.1, 1.0, 10, 100 mg/L was
      used to cultivate Nostoc flagelliforme cell at 25 degrees C and light intensity
      of 80 micromol/(m x s). Electrolyte leakage, the activities of superoxide
      dismutase, the content of malondialdehyde, proline, soluble protein and trehalose
      were analyzed. RESULTS: Under 1 - 100 mg/L Cu2+, Cr2+ and Pb2+ stress,
      electrolyte leakage and malondialdehyde contents in Nostoc flagelliforme cell
      were higher than those in the control group during heavy metal ions stress.
      Meanwhile, superoxide dismutase activity increased slightly under 10 mg/L, but
      was lower afterwards. The contents of proline, soluble protein and trehalose
      increased under 10 mg/L heavy metal ions stress, while declined under extreme
      heavy metal ions stress (100 mg/L). CONCLUSION: Nostoc flagelliforme cell has
      resistance to low heavy metal ions stress, but is damaged badly under extreme
      heavy metal ions stress.

PMID- 24028058
TI  - [Gene cloning and characterization of a solvent-resistant glucose dehydrogenase
      from Bacillus sp. YX-1].
AB  - OBJECTIVE: A gene encoding solvent-resistant glucose dehydrogenase was cloned
      from Bacillus sp. YX-1 and expressed in Escherichia coli. The recombinant enzyme
      was then characterized. METHODS: The glucose dehydrogenase gene was amplified
      from Bacillus sp. YX-1 genome according to its conserved sequences in Bacillus
      sp. The recombinant enzyme was over-expressed in E. coli and purified by HisTrap
      HP affinity chromatography. The purified enzyme were characterized. RESULTS: The
      glucose dehydrogenase gene contains an open reading frame of 786 bp encoding 261
      amino acids. The maximum activity was observed at 45 degrees C and pH 8.0. The
      recombinant enzyme was highly resistant to several organic solvents. More than
      90% of the activity was maintained when the enzyme was incubated in 50%
      cyclohexane, octane, decane at home temperature for 1 h. In addition, the enzyme
      displayed broad substrate spectrum and has catalytic activity for several sugars
      to afford reduced coenzymes. It exhibits similar capability to regenerate either
      NADH or NADPH with specific activity of 8.37 U/mg and 8.62 U/mg for NAD+ and
      NADP+. CONCLUSION: The organic solvent-tolerant glucose dehydrogenase was
      explored successfully on the basis of bioinformatics analysis. The work supplied
      a new biocatalyst for the cofactor-regeneration during the reaction in organic
      phases catalyzed by oxidoreductases.

PMID- 24028059
TI  - [Diversity of crenarchaeota in terrestrial hot springs and their surrounding
      environments in Kamchatka, Russia].
AB  - OBJECTIVE: Crenarchaeota is a major archaeal lineage in terrestrial hot springs
      and important in biogeochemical cycles of life-essential elements. In this study,
      we investigated the diversity of Crenarchaeota in hot springs and the surrounding
      environments in Kamchatka, Russia. In addition, we compared crenarchaeotal
      community structures in Kamchatka, Russia and Yunnan province, China. METHODS:
      Crenarchaeal 16S rRNA gene clone libraries were constructed and the sequences and
      abundances of representational clone were obtained. Phylogenetic analysis was
      then performed and the community structures in different samples were compared.
      RESULTS: The high temperature spring Burlyashi Liza (BSL, 89 degrees C) comprised
      Thermoprotei. The moderate temperature spring TF Vent 2 (TFV, 49 degrees C)
      harbored unidentified Thermoprotei group, unidentified crenarchaeal group, HWCG
      II (hot water crenarchaeotal group II), and Group1. 1b (one thaumarchaeotal
      subgroup). Most of sequences that obtained from surrounding environments ( <15
      degrees C) are closely with the representational clone pJP from a Yellowstone hot
      spring. Jackknife cluster and Principal coordinates analysis (PCoA) showed that
      the samples have more similarity in crenarchaeal communities at similar
      temperatures. CONCLUSION: The diversities of Crenarchaeota in Kamchatka hot
      springs are somewhat different from those in Yunnan province. Terrestrial hot
      springs obviously affect the crenarchaeotal communities in surrounding
      environments. Temperature is the major factor controlling the community structure
      in terrestrial hot springs.

PMID- 24028060
TI  - [Diversity of fe-hydrogenase microbe in Guizhou red paddy soil during flooding
      incubation].
AB  - OBJECTIVE: The diversity of Fe-hydrogenase based on Fe-hydrogenase gene of
      Clostridium was studied for exploring the biochemical mechanism of soil microbial
      hydrogen production and revealing the Fe-hydrogenase microbial community
      structure changes during the paddy soil flooding incubation. METHODS: We used
      denatured gradient gel electrophoresis and real-time quantitative PCR to achieve
      the goal. RESULTS: The band number of Fe-hydrogenase denatured gradient gel
      electrophoresis fingerprints indicated Fe-hydrogenase microbes structure varied
      significantly during the completely flooding incubation. The Principal Component
      Analysis (PCA) showed the highly similar communities of Fe-hydrogenase microbial
      was divided into three groups: 1 d and 20 d, the 5 d, 30 d and 40 d. With the
      growth of the flooding incubation time Fe-hydrogenase microbial community
      structure became relatively stable and convergence. Alpha diversity index
      analysis found that the richness index (R), Shannon-Weaver index (H'), Simpson
      index (D(S)) numerical values of 1 d and 10 d were lower compared with other
      points, indicated the two time points of low Fe-hydrogenase diversity, simple Fe
      hydrogenase microbial community structure and successive variation of community
      structure during the whole flooding incubation. After sequencing 15 Fe
      hydrogenase preponderant bands ( labeled by G1 - G15), the phylogenetic tree of
      Fe-hydrogenase showed that the preponderant bands all had high similarity with
      the Clostridium Fe-hydrogenase in earlier flooding incubation stage and non
      Clostridium Fe-hydrogenase in the later stage. Real-time quantitative PCR results
      demonstrated that the Fe-hydrogenase gene copy number was 10(6) level.
      CONCLUSION: In the research we found 4 kinds of Clostridium Fe-hydrogenases and
      three kinds of non-Clostridium Fe-hydrogenases, the corresponding Fe-hydrogenase
      microbial community structure had successively significant variation in the early
      incubation stage and tend to be relatively stable and convergence in the late
      stage.

PMID- 24028061
TI  - [Construction of baculovirus vector with Cytomegaloviruse promoter to express
      eGFP in primary chicken embryo cells].
AB  - OBJECTIVE: Baculovirus is known as a safe vector candidate due to its non
      replication in mammalian cells. The tropism to different cells and transduction
      efficiency can be improved by introducing cell-specific promoter, VSV-GED and
      different functional regulatory elements. The optimized pseudotyped recombinant
      baculovirus can express eGFP gene in primary chicken cells, which provides us a
      new approach to develop engineered poultry vaccines. METHOD: The pseudotyped
      recombinant baculoviruses were constructed with cytomegaoviyns (CMV) promotor,
      VSV-GED, woodchuck hepatitis virus post-transcriptional regulatory element (WPRE)
      and inverted terminal repeats (ITRs). The recombinant baculoviruses contained
      eGFP reporter gene were transfected chicken primary cells, and the eGFP protein
      expression levels mediated by different baculoviruses were analyzed. RESULTS: The
      expression of eGFP was detected at 12 hours after infection. The transduction
      efficiency of the pseudotyped recombinant baculoviruses increased from 36% to
      48.2% by inserting VSV-GED. The expression effect of eGFP in recombinant
      baculovirus carrying WPRE element was similar to that by adding 10 mmol/L
      butyrate. However, the WPRE elements are nontoxic to cells. Within 72 hours, the
      expression intensity of eGFP in the recombinant baculovirus with ITRs increased
      gradually. CONCLUSION: The VSV-GED element can improve the transduction
      efficiency and WPRE can increase the reporter gene eGFP expression levels
      mediated by baculovirus in chicken primary cells. The recombinant baculovirus
      with the ITRs elements can extend the expression time of eGFP.

PMID- 24028062
TI  - [Evaluation of synthetic peptide vaccines against foot-and-mouth disease type A].
AB  - OBJECTIVE: We developed a synthetic vaccine against foot-and-mouth disease type
      A. METHODS: We studied two peptide-based vaccines containing residues 131 to 159
      of VP1, 20 to 35 of VP4, 21 to 35 of 3A and 29 to 42 of 3B of the AF/72 strain of
      foot-and-mouth disease virus (FMDV) coupled with a CpG oligodeoxynucleotide (5'
      TCGCGAACGTTCGCCCGATCGTCGGTA-3') in guinea pigs. We assayed the FMDV-specific IgG
      level, serum neutralizing antibody titer, splenic lymphocytes proliferative
      capacity and peripheral blood T lymphocyte CD4-CD8 subsets distribution. RESULTS:
      The data show that high dose did not ensure a good immunity. In our study, 8%
      (4/5) of peptide 364-2.5-inoculated guinea pigs (2.5 microg of peptide 364 per
      animal) were protected against AF/72 strain challenge, while the protection ratio
      from other peptide-immunized groups was lower except the inactivated vaccine
      inoculated group which showed a full protection. Our results also indicated that
      the stimulatory ability of CD4+ T lymphocyte response played a key role in
      evaluating effective FMDV vaccine. The highest percentage of CD4+ T lymphocyte
      was 36.6% appeared in inactivated vaccine-immunized guinea pigs, the second was
      33.7% in peptide 364-2.5-vaccinated group, whereas the remaining ranged from
      18.1% to 27.7%. There was no obvious relation between CD8+ T cells and anti-FMDV
      infection; our data showed that the CD4/CD8 ratio was not always appropriate for
      assessing the immune system status. CONCLUSION: In general, we not only designed
      an effective vaccine against FMDV type A, but also discovered some useful
      information of humoral and cellular responses induced by foot-and-mouth disease
      vaccines.

PMID- 24028063
TI  - [Construction of Escherichia coli gene knock-out mutants for engineering of fatty
      acid metabolism].
AB  - OBJECTIVE: Gene knock out technique is very important for gene function study. We
      developed a simple and efficient method to knock out chromosomal genes in
      Escherichia coli. METHODS: Using the Escherichia coli Keio single-mutant library,
      we combined Red homology recombination with P1 phage transduction and developed a
      method to knock out the genes in Escherichia coli MG1655. RESULTS: We obtained
      beta-oxidation mutants deltafadD, deltafadE and deltafadD-deltafadE and fatty
      acid synthesis mutants deltafabH, deltafabF and deltafabH-deltafabF. There were
      no obvious growth changes between deltafadD or deltafadE mutant strains and
      MG1655. However, deltafabH and deltafabH-deltafabF mutant strains grew much
      slower than the wild type strain. The fatty acid contents in deltafadD, deltafadE
      and deltafadD-deltafadE were 18.2 mg/L, 20.0 mg/L and 19.2 mg/L respectively,
      higher than 17.5 mg/L in wild type. The fatty acid contents in deltafabH,
      deltafabF and deltafabH-deltafabF were 12.6 mg/L, 15.2 mg/L and 11.2mg/L
      respectively, lower than that in wild type. CONCLUSION: Using Keio mutant
      library, P1 phage transduction and resistant gene elimination, we have
      established a simple and efficient method for gene knock-out in Escherichia coli.

PMID- 24028064
TI  - [Effect of clpP disruption on alkaline sensitivity of Bacillus thuringiensis].
AB  - OBJECTIVE: We compared alkaline tolerance between Bacillus thuringiensis (Bt) and
      B. subtilis (Bs) and to determine the effect on growth when the clpP gene
      encoding caseinolytic protease is disrupted after alkaline shock. METHODS: B.
      thuringiensis HD73 mutant with the deletion of clpP gene was constructed by
      homologous recombination. The effects of clpP deletion on the growth after
      alkaline shock, sporulation and germination were analyzed. RESULTS: Bt can
      recover growth from alkaline shock when the medium pH was between 8.9 and 9.1
      whereas that was between 8.2 and 8.4 for Bs. Bt tolerated alkaline more than Bs,
      leading Bt to adapt in alkaline environment of the midgut as a pathogen of
      insect. Deletion of clpP gene had no influence on sporulation and germination.
      The clpP mutant grew slower than Bt HD73 in the LB medium in addition to NaOH of
      30 mmol/L. It indicates that the ClpP plays an important role in the alkaline
      tolerance of Bt strain.

PMID- 24028065
TI  - [Cloning and sequence characterization of replication region in plasmid pJTU112
      from Micoromonospora sp. 40027].
AB  - Micoromonospora sp. 40027, the producer of fortimicin A, harbors two plasmids
      pJTU101 and pJTU112. OBJECTIVE: Cloning and sequencing of replication region of
      pJTU12, analyzing replication region sequence of pJTU112. METHODS: Different
      fragments of pJTU112 were cloned and introduced by conjugation into
      Micromonospora sp. LXH20. The replication region of pJTU112 was identified.
      RESULTS: The replication region of pJTU112 was located in the 4.7 kb SacI-KpnI
      DNA fragment. DNA sequencing and analysis revealed that the 4.7 kb SacI-KpnI DNA
      fragment encoded five open reading frames. The pJTU112.1 and pJTU112.2 were
      related to plasmid conjugation, pJTU112.3, pJTU112.4 and pJTU112.5 were related
      to plasmid conjugation. CONCLUSION: The replication region of pJTU112 was located
      in the 4.7kb SacI-KpnI DNA fragment.

PMID- 24028066
TI  - [Identification of Vibrio metschnikovii from Homarus americanus and its changes
      in membrane fatty acid composition in response to low temperature].
AB  - OBJECTIVE: Bacterial strain F5-1 isolated from the Homarus americanus was
      characterized and its changes in membrane fatty acid composition in response to
      low temperature were also studied. METHODS: The physiological and biochemical
      characteristics were carried out by using VITEK 2 compact automated microbiology
      system. The 16S rRNA gene was sequenced and subjected to phylogenetic analysis.
      Fatty acids were detected by gas chromatography-mass spectrometry (GC-MS).
      RESULTS: Strain F5-1 was Gram-negative and susceptible to the vibriostatic agent
      O/129. Strain F5-1 was resistant to Penicillin. The isolated strain exhibited the
      highest levels of 99% probability to Vibrio metschnikovii based on the
      conventional physiological test. The sequence analysis of 16S rRNA gene of F5-1
      isolation and comparison with that of other related vibrios showed that F5-1 was
      very close to V. metschnikovii (GenBank No. HQ658055). The similarity was 99%.
      The major fatty acids were C12:0, C14:0, C16:0 and C16:1 (n-7). Palmitoleic acid
      was the dominant unsaturated fatty acids. The major change in fatty acid
      composition occurred in response to low temperature, with an increase in
      palmitoleic acid from 34% to 40%. CONCLUSION: Bacterial strain F5-1 isolated from
      Homarus americanus was identified as V. metschnikovii and was sensitive to
      multiple drugs. The fatty acid composition of F5-1 was different from V.
      metschnikovii isolated from a drinking water reservoir near Vladivostok City in
      the Russia Far East. Results of this study indicated that environmental
      conditions allowed modulation of the fatty acid composition of V. metschnikovii.

PMID- 24028067
TI  - Identification of a possible secondary picrotoxin-binding site on the GABA(A)
      receptor.
AB  - The type A GABA receptors (GABARs) are ligand-gated ion channels (LGICs) found in
      the brain and are the major inhibitory neurotransmitter receptors. Upon binding
      of an agonist, the GABAR opens and increases the intraneuronal concentration of
      chloride ions, thus hyperpolarizing the cell and inhibiting the transmission of
      the nerve action potential. GABARs also contain many other modulatory binding
      pockets that differ from the agonist-binding site. The composition of the GABAR
      subunits can alter the properties of these modulatory sites. Picrotoxin is a
      noncompetitive antagonist for LGICs, and by inhibiting GABAR, picrotoxin can
      cause overstimulation and induce convulsions. We use addition of picrotoxin to
      probe the characteristics and possible mechanism of an additional modulatory
      pocket located at the interface between the ligand-binding domain and the
      transmembrane domain of the GABAR. Picrotoxin is widely regarded as a pore
      blocking agent that acts at the cytoplasmic end of the channel. However, there
      are also data to suggest that there may be an additional, secondary binding site
      for picrotoxin. Through homology modeling, molecular docking, and molecular
      dynamics simulations, we show that binding of picrotoxin to this interface pocket
      correlates with these data, and negative modulation occurs at the pocket via a
      kinking of the pore-lining helices into a more closed orientation. 

PMID- 24028069
TI  - Rational design of helical nanotubes from self-assembly of coiled-coil lock
      washers.
AB  - Design of a structurally defined helical assembly is described that involves
      recoding of the amino acid sequence of peptide GCN4-pAA. In solution and the
      crystalline state, GCN4-pAA adopts a 7-helix bundle structure that resembles a
      supramolecular lock washer. Structurally informed mutagenesis of the sequence of
      GCN4-pAA afforded peptide 7HSAP1, which undergoes self-association into a
      nanotube via noncovalent interactions between complementary interfaces of the
      coiled-coil lock-washer structures. Biophysical measurements conducted in
      solution and the solid state over multiple length scales of structural hierarchy
      are consistent with self-assembly of nanotube structures derived from 7-helix
      bundle subunits. The dimensions of the supramolecular assemblies are similar to
      those observed in the crystal structure of GCN4-pAA. Fluorescence studies of the
      interaction of 7HSAP1 with the solvatochromic fluorophore PRODAN indicated that
      the nanotubes could encapsulate shape-appropriate small molecules with high
      binding affinity. 

PMID- 24028068
TI  - Reducing levels of toxic RNA with small molecules.
AB  - Myotonic dystrophy (DM) is one of the most common forms of muscular dystrophy. DM
      is an autosomal dominant disease caused by a toxic gain of function RNA. The
      toxic RNA is produced from expanded noncoding CTG/CCTG repeats, and these
      CUG/CCUG repeats sequester the Muscleblind-like (MBNL) family of RNA binding
      proteins. The MBNL proteins are regulators of alternative splicing, and their
      sequestration has been linked with mis-splicing events in DM. A previously
      reported screen for small molecules found that pentamidine was able to improve
      splicing defects associated with DM. Biochemical experiments and cell and mouse
      model studies of the disease indicate that pentamidine and related compounds may
      work through binding the CTG*CAG repeat DNA to inhibit transcription. Analysis of
      a series of methylene linker analogues of pentamidine revealed that heptamidine
      reverses splicing defects and rescues myotonia in a DM1 mouse model. 

PMID- 24028070
TI  - Vitamin D deficiency, insulin resistance, and ventricular hypertrophy in the
      early stages of chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with markedly increased
      cardiovascular (CV) risk. This increase is not fully explained by traditional CV
      risk factors but may in part be mediated by nontraditional risk factors, such as
      inadequate vitamin D (vit D) levels and insulin resistance (IR). Although IR is
      shown in nondiabetic CKD, its association with vit D deficiency and vascular
      disease in this population is unknown and what this study aims to investigate.
      MATERIALS AND METHODS: The study comprised 67 patients with CKD (eGFR >= 30
      mL/min) and 15 healthy controls matched for age and sex. The phlogosis indexes,
      vit D levels, IR, carotid intima-media thickness (cIMT), and left ventricular
      mass index (LVMI) were measured. RESULTS: In our study, the mean value of LVMI
      and cIMT was significantly higher in patients with eGFR >= 30 mL/min compared
      with controls (p = 0.037 and p < 0.001). The IR and intact parathyroid hormone
      (iPTH) levels were increased in CKD patients, whereas the serum levels of vit D
      were significantly reduced (p = 0.044, p = 0.012, p = 0.038). A positive
      correlation was found between LVMI and IR (r = 0.704, p = 0.041) and a negative
      correlation was found between IR and vit D levels (r = -0.238, p = 0.031).
      CONCLUSIONS: In our study, IR and vit D deficiency were found to be independent
      predictors of left ventricular hypertrophy and atherosclerotic disease. Vitamin D
      deficiency and IR are thus associated with increased CV risk. More novel
      approaches to improving IR and vit D supplementation in the CKD population might
      lead to potential strategies for preventing excess CV mortality.

PMID- 24028071
TI  - Release of small phenolic compounds from brewer's spent grain and its lignin
      fractions by human intestinal microbiota in vitro.
AB  - Brewer's spent grain (BSG), the major side-stream from brewing, is rich in
      protein, lignin, and nonstarch polysaccharides. Lignin is a polyphenolic
      macromolecule considered resilient toward breakdown and utilization by colon
      microbiota, although some indications of release of small phenolic components
      from lignin in animals have been shown. The aim of this study was to investigate
      if the human intestinal microbiota can release lignans and small phenolic
      compounds from whole BSG, a lignin-enriched insoluble fraction from BSG and a
      deferuloylated fraction, in a metabolic in vitro colon model. The formation of
      short-chain fatty acid (SCFA) was also investigated. More lignin-related monomers
      and dilignols were detected from the lignin-enriched fraction than from BSG or
      deferuloylated BSG. SCFA formation was not suppressed by any of the fractions. It
      was shown that small lignin-like compounds were released from these samples in
      the in vitro colon model, originating most likely from lignin. 

PMID- 24028072
TI  - Photoluminescence, redox properties, and electrogenerated chemiluminescence of
      twisted 9,9'-bianthryls.
AB  - To study the dual emission (from locally excited and charge transfer states) of
      sterically crowded 9,9'-bianthryl (BAHO) and its 10,10'-disubstituted
      derivatives, namely, 10,10'-dibromo-9,9'-bianthryl (BABR), 10,10'-bis(p
      tolylethynyl)-9,9'-bianthryl (BAET), and 10,10'-bis(N,N-diphenyl-4-anilino)-9,9'
      bianthryl (BATA) in detail, we probed their photophysical, redox, and
      electrogenerated chemiluminescence (ECL) responses. Dual emission for all of the
      molecules was noticed in PL, whereas in ECL only charge transfer emission was
      observed over a variety of experimental conditions. The PL in nonpolar solvents
      is significantly influenced by added supporting electrolyte, yielding exclusively
      charge transfer emission as in ECL. The stability of ECL proved to depend largely
      on the nature of the substituent, with triarylamine and bromo groups imparting
      constant ECL intensity over more than 60 cycles. 

PMID- 24028073
TI  - CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement
      responsive to steroids. Review of an increasingly recognized entity within the
      spectrum of inflammatory central nervous system disorders.
AB  - Chronic lymphocytic inflammation with pontine perivascular enhancement responsive
      to steroids (CLIPPERS) is a recently defined inflammatory central nervous system
      (CNS) disorder, prominently involving the brainstem and in particular the pons.
      The condition features a combination of clinical symptoms essentially referable
      to brainstem pathology and a characteristic magnetic resonance imaging (MRI)
      appearance with punctate and curvilinear gadolinium enhancement 'peppering' the
      pons. The radiological distribution is focused in the pons and adjacent
      rhombencephalic structures such as the cerebellar peduncles, cerebellum, medulla
      and the midbrain. While the lesion burden with a perivascular pattern is
      typically most dense in these pontine and peripontine regions, enhancing lesions
      may additionally extend into the spinal cord and supratentorial structures such
      as the thalamus, basal ganglia, capsula interna, corpus callosum and the cerebral
      white matter. Another core feature is clinical and radiological responsiveness to
      glucocorticosteroid (GCS)-based immunosuppression. As withdrawal of GCS treatment
      results commonly in disease exacerbation, long-term immunosuppressive therapy
      appears to be mandatory for sustained improvement. Diagnosis of CLIPPERS is
      challenging, and requires careful exclusion of alternative diagnoses. A specific
      serum or cerebrospinal fluid (CSF) biomarker for the disorder is currently not
      known. Pathogenesis of CLIPPERS remains poorly understood, and the nosological
      position of CLIPPERS has still to be established. Whether CLIPPERS represents an
      independent, actual new disorder or a syndrome that includes aetiologically
      heterogeneous diseases and/or their prestages remains a debated and not finally
      clarified issue. Clinicians and radiologists should be aware of this condition
      and its differential diagnoses, given that CLIPPERS constitutes a treatable
      condition and that patients may benefit from an early introduction of GCS ensued
      by long-term immunosuppression. Based on previous reports in literature -
      currently encompassing more than 50 reported cases of CLIPPERS - this review
      addresses clinical features, diagnostic criteria, differential diagnoses and
      therapeutic management of this peculiar disorder.

PMID- 24028074
TI  - Syndromic surveillance for evaluating the occurrence of healthcare-associated
      infections in equine hospitals.
AB  - REASONS FOR PERFORMING STUDY: Methods that can be used to estimate rates of
      healthcare-associated infections and other nosocomial events have not been well
      established for use in equine hospitals. Traditional laboratory-based
      surveillance is expensive and cannot be applied in all of these settings.
      OBJECTIVES: To evaluate the use of a syndromic surveillance system for estimating
      rates of occurrence of healthcare-associated infections among hospitalised equine
      cases. STUDY DESIGN: Multicentre, prospective longitudinal study. METHODS: This
      study included weaned equids (n = 297) that were admitted for gastrointestinal
      disorders at one of 5 participating veterinary referral hospitals during a 12
      week period in 2006. A survey form was completed by the primary clinician to
      summarise basic case information, procedures and treatments the horse received,
      and whether one or more of 7 predefined nosocomial syndromes were recognised at
      any point during hospitalisation. Adjusted rates of nosocomial events were
      estimated using Poisson regression. Risk factors associated with the risk of
      developing a nosocomial event were analysed using multivariable logistic
      regression. RESULTS: Among the study population, 95 nosocomial events were
      reported to have occurred in 65 horses. Controlling for differences among
      hospitals, 19.7% (95% confidence interval, 14.5-26.7) of the study population was
      reported to have had at least one nosocomial event recognised during
      hospitalisation. The most commonly reported nosocomial syndromes that were
      unrelated to the reason for hospitalisation were surgical site inflammation and
      i.v. catheter site inflammation. CONCLUSIONS: Syndromic surveillance systems can
      be standardised successfully for use across multiple hospitals without
      interfering with established organisational structures, in order to provide
      useful estimates of rates related to healthcare-associated infections.

PMID- 24028075
TI  - Comparing atomistic molecular mechanics force fields for a difficult target: a
      case study on the Alzheimer's amyloid beta-peptide.
AB  - Macromolecular function arises from structure, and many diseases are associated
      with misfolding of proteins. Molecular simulation methods can augment
      experimental techniques to understand misfolding and aggregation pathways with
      atomistic resolution, but the reliability of these predictions is a function of
      the parameters used for the simulation. There are many biomolecular force fields
      available, but most are validated using stably folded structures. Here, we
      present the results of molecular dynamics simulations on the intrinsically
      disordered amyloid beta-peptide (Abeta), whose misfolding and aggregation give
      rise to the symptoms of Alzheimer's disease. Because of the link between
      secondary structure changes and pathology, being able to accurately model the
      structure of Abeta would greatly improve our understanding of this disease, and
      it may facilitate application of modeling approaches to other protein misfolding
      disorders. To this end, we compared five popular atomistic force fields (AMBER03,
      CHARMM22 + CMAP, GROMOS96 53A6, GROMOS96 54A7, and OPLS-AA) to determine which
      could best model the structure of Abeta. By comparing secondary structure
      content, NMR shifts, and radius of gyration to available experimental data, we
      conclude that AMBER03 and CHARMM22 + CMAP over-stabilize helical structure within
      Abeta, with CHARMM22 + CMAP also producing elongated Abeta structures, in
      conflict with experimental findings. OPLS-AA, GROMOS96 53A6, and GROMOS96 54A7
      produce very similar results in terms of helical and beta-strand content,
      calculated NMR shifts, and radii of gyration that agree well with experimental
      data. 

PMID- 24028076
TI  - Clinical impact of LH rises prior to and during ganirelix treatment started on
      day 5 or on day 6 of ovarian stimulation.
AB  - BACKGROUND: We sought to evaluate the incidence and clinical impact of
      luteinizing hormone (LH) rises prior to and during gonadotropin-releasing hormone
      (GnRH) antagonist treatment started on day 5 or 6 of ovarian stimulation with
      recombinant follicle-stimulating hormone (rFSH). METHODS: Pooled data from three
      trials with the GnRH antagonist ganirelix started on day 5 (n = 961) and from
      five trials with ganirelix started on day 6 (n = 1135) of ovarian stimulation
      with rFSH were retrospectively analyzed. RESULTS: The incidence of LH rises (LH
      >= 10.0 IU/L) prior to ganirelix treatment was 2.3% and 6.6% on ganirelix start
      days 5 and 6, respectively (P < 0.01). During ganirelix treatment this incidence
      was 1.2% and 2.3%, respectively (P = 0.06). Women with LH rise on day 5 or 6 had
      a higher ovarian response with more oocytes recovered, mean +/- SD, 12.9 +/- 8.5
      versus no LH rise, 10.2 +/- 6.4 (P < 0.01). In women with and without LH rise
      prior to ganirelix treatment the ongoing pregnancy rates were similar (26.0% vs
      29.9%; odds ratio [OR], 0.89; 95% confidence interval [CI], 0.55-1.44). Women
      with LH rise during ganirelix treatment had a lower ovarian response with 7.5 +/-
      6.7 oocytes recovered versus no LH rise, 10.2 +/- 6.4 (P = 0.02) and a tendancy
      for a lower chance of ongoing pregnancy (16.7% vs 29.9%; OR, 0.52; 95% CI, 0.21
      1.26). CONCLUSIONS: The incidence of early and late LH rises was low but may be
      further reduced by initiating ganirelix on stimulation day 5 rather than on day
      6. In contrast to women with an early LH rise, women with a late LH rise may have
      a reduced chance of ongoing pregnancy.

PMID- 24028077
TI  - The globular heads of the C1q receptor regulate apoptosis in human extravillous
      cytotrophoblast-derived transformed cells via a mitochondria-dependent pathway.
AB  - PROBLEM: The receptor for the globular head of human C1q (gC1qR) predominantly
      localizes to the mitochondrial matrix. gC1qR mediates many biological responses,
      including growth perturbations, morphological abnormalities and the initiation of
      apoptosis. The purpose of this study was to investigate the relationship between
      gC1qR expression, mitochondrial dysfunction and the regulation of apoptosis in
      human extravillous cytotrophoblast (EVCT)-derived transformed cell lines (HTR
      8/SVneo and HPT-8). METHOD OF STUDY: gC1qR expression was examined in human
      placental villi using real-time qPCR and Western blot analysis. The apoptotic
      death of HTR-8/SVneo and HPT-8 cells was assessed using flow cytometric analysis.
      Mitochondrial function was assessed via ROS generation, the amount of cytosolic
      Ca(2+) and changes in the mitochondrial membrane potential (Deltapsim). RESULTS:
      The expression of the gC1qR gene was significantly increased in spontaneous
      abortion samples relative to induced abortion samples. HTR-8/SVneo and HPT-8
      cells transfected with a gC1qR vector showed upregulation of cellular apoptosis
      and mitochondrial dysfunction, interestingly, which were abrogated by the
      addition of metformin. Metformin may protect mitochondrial function. CONCLUSION:
      These data support a mechanism whereby gC1qR induces apoptosis through
      mitochondria-dependent pathways in human EVCT-derived transformed cells.

PMID- 24028078
TI  - Genotyping of human neutrophil antigens (HNA) from whole genome sequencing data.
AB  - BACKGROUND: Neutrophil antigens are involved in a variety of clinical conditions
      including transfusion-related acute lung injury (TRALI) and other transfusion
      related diseases. Recently, there are five characterized groups of human
      neutrophil antigen (HNA) systems, the HNA1 to 5. Characterization of all
      neutrophil antigens from whole genome sequencing (WGS) data may be accomplished
      for revealing complete genotyping formats of neutrophil antigens collectively at
      genome level with molecular variations which may respectively be revealed with
      available genotyping techniques for neutrophil antigens conventionally. RESULTS:
      We developed a computing method for the genotyping of human neutrophil antigens.
      Six samples from two families, available from the 1000 Genomes projects, were
      used for a HNA typing test. There are 500 ~ 3000 reads per sample filtered from
      the adopted human WGS datasets in order for identifying single nucleotide
      polymorphisms (SNPs) of neutrophil antigens. The visualization of read alignment
      shows that the yield reads from WGS dataset are enough to cover all of the SNP
      loci for the antigen system: HNA1, HNA3, HNA4 and HNA5. Consequently, our
      implemented Bioinformatics tool successfully revealed HNA types on all of the six
      samples including sequence-based typing (SBT) as well as PCR sequence-specific
      oligonucleotide probes (SSOP), PCR sequence-specific primers (SSP) and PCR
      restriction fragment length polymorphism (RFLP) along with parentage possibility.
      CONCLUSIONS: The next-generation sequencing technology strives to deliver
      affordable and non-biased sequencing results, hence the complete genotyping
      formats of HNA may be reported collectively from mining the output data of WGS.
      The study shows the feasibility of HNA genotyping through new WGS technologies.
      Our proposed algorithmic methodology is implemented in a HNATyping software
      package with user's guide available to the public at
      http://sourceforge.net/projects/hnatyping/.

PMID- 24028079
TI  - HAM-2 and HAM-3 are central for the assembly of the Neurospora STRIPAK complex at
      the nuclear envelope and regulate nuclear accumulation of the MAP kinase MAK-1 in
      a MAK-2-dependent manner.
AB  - Intercellular communication and somatic cell fusion are important for fungal
      colony establishment, multicellular differentiation and have been associated with
      host colonization and virulence of pathogenic species. By a combination of
      genetic, biochemical and live cell imaging techniques, we characterized the
      Neurospora crassa STRIPAK complex that is essential for self-signalling and
      consists of the six proteins HAM-2/STRIP, HAM-3/striatin, HAM-4/SLMAP, MOB
      3/phocein, PPG-1/PP2A-C and PP2A-A. We describe that the core STRIPAK components
      HAM-2 and HAM-3 are central for the assembly of the complex at the nuclear
      envelope, while the phosphatase PPG-1 only transiently associates with this
      central subcomplex. Our data connect the STRIPAK complex with two MAP kinase
      pathways: (i) nuclear accumulation of the cell wall integrity MAP kinase MAK-1
      depends on the functional integrity of the STRIPAK complex at the nuclear
      envelope, and (ii) phosphorylation of MOB-3 by the MAP kinase MAK-2 impacts the
      nuclear accumulation of MAK-1. In summary, these data support a model, in which
      MAK-2-dependent phosphorylation of MOB-3 is part of a MAK-1 import mechanism.
      Although self-communication remained intact in the absence of nuclear MAK-1
      accumulation, supporting the presence of multiple mechanisms that co-ordinate
      robust intercellular communication, proper fruiting body morphology was dependent
      on the MAK-2-phosphorylated N-terminus of MOB-3. 

PMID- 24028082
TI  - TAK1 promotes cell survival by TNFAIP3 and IL-8 dependent and NF-kappaB
      independent pathway in HeLa cells exposed to heat stress.
AB  - PURPOSE: Transforming growth factor-beta-activated kinase 1 (TAK1) plays a role
      in inhibiting apoptosis in response to multiple stresses. In the present study,
      we investigated the role of TAK1 in cell death induced by heat stress (HS).
      MATERIALS AND METHODS: TAK1 knockdown HeLa cells and their parental cells were
      exposed to HS at 44  degrees C for 15, 30, 45 min followed by colony formation
      assay. Heat shock proteins (HSPs) induction, NF-kappaB phosphorylation, and
      caspase-3 cleavage were estimated by western blotting using specific antibodies.
      Global gene expression analysis was performed using the GeneChip(r) system. The
      anti-apoptotic roles of the identified genes were elucidated using small
      interfering RNAs targeting those genes. RESULTS: Heat sensitivity estimated by
      colony formation assay and caspase-3 cleavage increased in TAK1 knockdown cells.
      This sensitisation was not due to alterations in HSP induction or NF-kappaB
      phosphorylation as the expression levels of these proteins did not differ
      significantly between the TAK1 knockdown and the parent cells after HS exposure.
      The GeneChip(r) analysis revealed differences in gene expression between both
      cell variants after HS exposure and defined the genetic network associated with
      cell death. TNF-alpha interacting protein 3 (TNFAIP3) and Interleukin 8 (IL-8)
      are two of the identified genes. RNA interference against these genes increased
      the cleavage of caspase-3 and cell death after HS exposure. CONCLUSION: Our
      findings reveal the role of TAK1 in thermoresistance and show that the mediation
      is independent of NF-kappaB phosphorylation but is dependent on TNFAIP3 and IL-8
      induction.

PMID- 24028084
TI  - Parents' constructions of communication with their children about safer sex.
AB  - AIMS AND OBJECTIVES: To analyse how a sample of parents reportedly communicated
      with their adolescent and preadolescent children about safer sex (contraceptive
      and condom use). BACKGROUND: Among the plethora of existing research available on
      parent-child communication about sexuality (more broadly), very few studies
      detail the substance and tenor of what parents actually convey specifically about
      safer sex. DESIGN: The study adopted a qualitative methodology and involved
      interviewing 43 parents (32 mothers and 11 fathers). Data were analysed using
      modified analytical induction. RESULTS: Findings indicated that although the
      majority of parents professed to being open about sexuality with their children,
      only a minority reportedly conveyed direct messages about contraception and
      condom use. Moreover, these direct messages appeared to be imparted at a
      superficial level. Parents were more likely to communicate such messages in a
      tacit manner through innuendo and intimation. The complacency that parents
      displayed about the need to undertake safer sex education with their adolescents
      arose from an understanding that this was covered adequately at school and the
      belief that their teenager was not in a romantic relationship. In addition, some
      parents expressed concern that discussing safer sex with teenagers might actually
      encourage sexual activity. CONCLUSION: We conclude that some parents may consider
      themselves to have engaged in sexuality education around safer sex when it
      appears to be predominantly surface-level education; that what constitutes
      'doing' sexuality education is far from clear-cut may cast some light on why
      there is little consistency in the literature on the impact of parental
      communication on sexual health outcomes for young people. RELEVANCE TO CLINICAL
      PRACTICE: For nurses engaged in sexuality health promotion with parents, we
      caution about presenting unequivocal messages to parents about the impact of
      parental communication about sexuality on adolescent sexual behaviour without due
      acknowledgement of the grey areas indicated in the literature.

PMID- 24028083
TI  - Adapting the Trials of Improved Practices (TIPs) approach to explore the
      acceptability and feasibility of nutrition and parenting recommendations: what
      works for low-income families?
AB  - Interventions to prevent childhood obesity must consider not only how child
      feeding behaviours are related to child weight status but also which behaviours
      parents are willing and able to change. This study adapted Trials of Improved
      Practices (TIPs) to assess acceptability and feasibility of nutrition and
      parenting recommendations, using in-depth interviews and household trials to
      explore families' experiences over time. A diverse sample of 23 low-income
      parents of 3-11-year-olds was recruited following participation in nutrition and
      parenting education. Parents chose nutrition and parenting practices to try at
      home and were interviewed 2 weeks and 4-6 months later about behaviour change
      efforts. Qualitative analysis identified emergent themes, and acceptability and
      feasibility were rated based on parents' willingness and ability to try new
      practices. The nutrition goal parents chose most frequently was increasing
      children's vegetable intake, followed by replacing sweetened beverages with water
      or milk, and limiting energy-dense foods. Parents were less inclined to reduce
      serving sizes. The parenting practices most often selected as applicable to
      nutrition goals were role-modelling; shaping home environments, often with other
      adults; involving children in decisions; and providing positive feedback. Most
      recommendations were viewed as acceptable by meaningful numbers of parents, many
      of whom tried and sustained new behaviours. Food preferences, habits and time
      were common barriers; family resistance or food costs also constrained some
      parents. Despite challenges, TIPs was successfully adapted to evaluate complex
      nutrition and parenting practices. Information on parents' willingness and
      ability to try practices provides valuable guidance for childhood obesity
      prevention programmes. 

PMID- 24028085
TI  - Peritoneal dialysis catheter placement with peritoneoscopic technique and
      successful initiation of peritoneal dialysis in a patient with diastasis recti.
AB  - Preserved anatomical integrity of the anterior abdominal wall is considered
      important in the presurgical evaluation of a patient who is being considered for
      placement of a peritoneal dialysis (PD) catheter. Diastasis recti abdominis (DRA)
      is the excessive widening or separation between the two bellies of the rectus
      abdominis muscle. The separation can occur anywhere along the linea alba and at
      times has been found to span the entire length from the xiphosternal angle to the
      pubic bone. Presence of DRA can pose a surgical challenge in the peritoneoscopic
      placement of peritoneal dialysis catheter. In this report, we discuss a case of
      successful placement of peritoneal dialysis catheter with peritoneoscope
      technique and successful initiation of peritoneal dialysis in a chronic kidney
      disease patient with DRA. 

PMID- 24028086
TI  - Drop rebound after impact: the role of the receding contact angle.
AB  - Data from the literature suggest that the rebound of a drop from a surface can be
      achieved when the wettability is low, i.e., when contact angles, measured at the
      triple line (solid-liquid-air), are high. However, no clear criterion exists to
      predict when a drop will rebound from a surface and which is the key wetting
      parameter to govern drop rebound (e.g., the "equilibrium" contact angle, thetaeq,
      the advancing and the receding contact angles, thetaA and thetaR, respectively,
      the contact angle hysteresis, Deltatheta, or any combination of these
      parameters). To clarify the conditions for drop rebound, we conducted
      experimental tests on different dry solid surfaces with variable wettability,
      from hydrophobic to superhydrophobic surfaces, with advancing contact angles 108
      degrees  < thetaA < 169 degrees  and receding contact angles 89 degrees  < thetaR
      < 161 degrees . It was found that the receding contact angle is the key wetting
      parameter that influences drop rebound, along with surface hydrophobicity: for
      the investigated impact conditions (drop diameter 2.4 < D0 < 2.6 mm, impact speed
      0.8 < V < 4.1 m/s, Weber number 25 < We < 585), rebound was observed only on
      surfaces with receding contact angles higher than 100 degrees . Also, the drop
      rebound time decreased by increasing the receding contact angle. It was also
      shown that in general care must be taken when using statically defined wetting
      parameters (such as advancing and receding contact angles) to predict the dynamic
      behavior of a liquid on a solid surface because the dynamics of the phenomenon
      may affect surface wetting close to the impact point (e.g., as a result of the
      transition from the Cassie-Baxter to Wenzel state in the case of the so-called
      superhydrophobic surfaces) and thus affect the drop rebound. 

PMID- 24028080
TI  - A rapid questionnaire assessment of environmental exposures to pregnant women in
      the INTERGROWTH-21st Project.
AB  - Impaired fetal growth and preterm birth are the leading causes of neonatal and
      infant mortality worldwide and there is a growing scientific literature
      suggesting that environmental exposures during pregnancy may play a causal role
      in these outcomes. Our purpose was to assess the environmental exposure of the
      Fetal Growth Longitudinal Study (FGLS) participants in the multinational
      INTERGROWTH-21(st) Project. First, we developed a tool that could be used
      internationally to screen pregnant women for such exposures and administered it
      in eight countries on a subsample (n = 987) of the FGLS participants. The FGLS is
      a study of fetal growth among healthy pregnant women living in relatively
      affluent areas, at low risk of adverse pregnancy outcomes and environmental
      exposures. We confirmed that most women were not exposed to major environmental
      hazards that could affect pregnancy outcomes according to the protocol's entry
      criteria. However, the instrument was able to identify some women that reported
      various environmental concerns in their homes such as peeling paint, high
      residential density (>1 person per room), presence of rodents or cockroaches
      (hence the use of pesticides), noise pollution and safety concerns. This
      screening tool was therefore useful for the purposes of the project and can be
      used to ascertain environmental exposures in studies in which the primary aim is
      not focused on environmental exposures. The instrument can be used to identify
      subpopulations for more in-depth assessment, (e.g. environmental and biological
      laboratory markers) to pinpoint areas requiring education, intervention or policy
      change.

PMID- 24028081
TI  - Translating research into practice: the introduction of the INTERGROWTH-21st
      package of clinical standards, tools and guidelines into policies, programmes and
      services.
AB  - The INTERGROWTH-21(st) Project has generated a package of international clinical
      standards, tools and guidelines. It is now necessary to plan for the next phase
      of the project: the translation of the research findings into practice through
      its global dissemination. The plan is to pre-empt barriers to implementation by
      drawing from the published literature; gathering views and perspectives from
      policy makers, programmers and practitioners; incorporating input from local
      'champions', and collecting and analysing data generated by a monitoring and
      evaluation system. Working at the global, regional, national and local levels
      will enable wide dissemination of the package, as well as increase the scope for
      adaptation and integration in diverse clinical contexts. We seek maximum uptake
      of the package in policies, guidelines and clinical practice to improve the
      quality of care offered to mothers and newborns. The strategy will also enhance
      our understanding of the effectiveness of different approaches to the translation
      of evidence into practice. 

PMID- 24028087
TI  - Experience-dependent persistent expression of zif268 during rest is preserved in
      the aged dentate gyrus.
AB  - BACKGROUND: Aging is typically accompanied by memory decline and changes in
      hippocampal function. Among these changes is a decline in the activity of the
      dentate gyrus (DG) during behavior. Lasting memory, however, is thought to also
      require recapitulation of recent memory traces during subsequent rest - a
      phenomenon, termed memory trace reactivation, which is compromised in hippocampal
      CA1 with progressive age. This process has yet to be assessed in the aged DG,
      despite its prominent role in age-related memory impairment. Using zif268
      transcription to measure granule cell recruitment, DG activity in adult and aged
      animals was assessed both during spatial exploration and as animals remained at
      rest in the home cage in order to detect potential memory-related replay.
      RESULTS: Consistent with the observation of memory trace reactivation in DG, the
      probability that an individual granule cell transcribes zif268 during rest in the
      animal's home cage is increased by recent experience in a novel environment.
      Surprisingly, a comparable increase was observed in the probability of granule
      cells in the aged DG expressing zif268 during rest. Moreover, no significant age
      related difference was observed in the number of granule cells expressing zif268
      during rest. Thus, the number and pattern of granule cell expression of zif268
      during rest is preserved in aged animals, despite a significant decline in
      exploration-related zif268 expression. CONCLUSIONS: These data lead to the
      hypothesis that the input the aged DG receives from backprojections from CA3 (the
      region widely hypothesized to mediate reactivation) remains functionally intact
      despite loss of innervation from the perforant path.

PMID- 24028088
TI  - Sustained improvement of gas exchange and lung mechanics by vaporized
      perfluorocarbon inhalation in piglet acute lung injury model.
AB  - INTRODUCTION: New methods for perfluorocarbon (PFC) application have been
      proposed which include aerosolization and vaporization. However, the experimental
      documentation of efficacy of vaporization of PFC in the treatment of acute
      respiratory distress syndrome (ARDS) is still lacking. OBJECTIVES: This study
      aims to examine the effects of vaporized PFC on gas exchange and lung mechanics
      in a piglet model with ARDS. METHODS: Lung injury was induced in 16 piglets by
      infusing detergent through tracheal intubation. Eight piglets were treated with
      vaporized PFC for 2 h followed by 6 h of volume-controlled ventilation. Another
      eight piglets receiving 8 h volume-controlled ventilation were used as controls.
      Blood gases, lung mechanical and hemodynamic parameters were measured. RESULTS:
      Vaporized PFC treatment significantly increased oxygenation index (P/F ratio) and
      static lung compliance (Cst) 2 h after therapy compared with the control group
      (P<0.05). The P/F ratio reached a peak 5.5 h after the therapy and remained at an
      increased level for at least 6 h compared with the control group (P<0.001).
      Additionally, 6 h post treatment, peak inspiratory pressure was significantly
      reduced in PFC group when compared with the control group (P<0.05), and Cst was
      significantly higher in the PFC group than in the control group (P=0.001).
      CONCLUSIONS: Inhalation of vaporized PFC results in sustained improvement of
      pulmonary gas exchange and lung mechanics in a detergent-induced animal model of
      lung injury. Therefore, the non-invasive vaporization application technique would
      be a reasonable alternative to administer perfluorocarbons in severe lung injury.

PMID- 24028089
TI  - The ubiquitin-proteasome system regulates the stability and activity of the
      glucose sensor glucokinase in pancreatic beta-cells.
AB  - The ubiquitin-proteasome system is important to maintain pancreatic beta-cell
      function. Inhibition of the proteasome significantly reduced glucose-induced
      insulin secretion. Key regulators of the stimulus/secretion cascade seem to be
      affected by protein misfolding if the proteasome is down-regulated as recently
      reported in humans with Type 2 diabetes. It remains unknown, however, whether the
      glucose sensor enzyme glucokinase is involved in this process. A direct
      interaction between glucokinase and ubiquitin could be shown in vivo by FRET,
      suggesting regulation of glucokinase by the proteasome. After proteasome
      inhibition glucokinase activity was significantly reduced in MIN6 cells, whereas
      the protein content was increased, indicating protein misfolding. Enhancing the
      availability of chaperones by cyclohexamide could induce refolding and restored
      glucokinase activity. Glucokinase aggregation due to proteasome blocking with
      MG132, bortezomib, epoxomicin or lactacystin could be detected in MIN6 cells,
      primary beta-cells and hepatocytes using fluorescence-based assays. Glucokinase
      aggresome formation proceeded microtubule-assisted and was avoided by
      cyclohexamide. Thus the results of the present study provide support for
      glucokinase misfolding and aggregation in case of a diminished capacity of the
      ubiquitin-proteasome system in pancreatic beta-cells. In the Type 2 diabetic
      situation this could contribute to reduced glucose-induced insulin secretion.

PMID- 24028090
TI  - Effect of lycopene on oxidative stress induced during D
      galactosamine/lipopolysaccharide-sensitized liver injury in rats.
AB  - CONTEXT: Lycopene is a phytonutrient under considerable investigation for its
      antioxidant benefits in treating diseases like cancer, cardiovascular diseases,
      osteoporosis and diabetes. OBJECTIVE: This study explores the effect of lycopene
      against oxidative damage during experimental hepatitis, induced by D
      galactosamine/lipopolysaccharide (D-GalN/LPS). MATERIALS AND METHODS:
      Experimental rats were pretreated with lycopene intraperitoneally for 6 d (10
      mg/kg body weight/day) and then induced by D-GalN/LPS. After induction, the
      levels of lipid peroxides in serum and liver of control and experimental group of
      animals were measured. The activities of enzymatic antioxidants such as
      superoxide dismutase, catalase, glutathione peroxidase and glutathione S
      transferase and nonenzymatic antioxidants, such as reduced glutathione, vitamin C
      and vitamin E were also analyzed. The genotoxic effect of D-GalN/LPS was
      evaluated through the comet assay. RESULTS: The elevated level of lipid peroxides
      induced by D-GalN/LPS was significantly (p < 0.05) reverted in lycopene
      pretreated animals. Lycopene administration restored (p < 0.05) the decreased
      activities of enzymatic and nonenzymatic antioxidant markers during D-GalN/LPS
      induction. The DNA strand breaks (72.3 MUM) generated during d-GalN/LPS toxic
      injury was significantly reduced (35.5 MUM) upon pretreatment with lycopene as
      observed by reduced tail movement in comet assay. DISCUSSION AND CONCLUSION:
      There is no conclusive report about lycopene-assisted protection against free
      radical mediated toxic injury induced by D-GalN/LPS. Our findings reveal that
      lycopene effectively combated oxidative damage and protected antioxidant defense
      status of the cell. Pretreatment of lycopene also offers protection against the
      DNA damage and confirms the antioxidant nature of the phytonutreint against
      experimental hepatitis.

PMID- 24028092
TI  - Perspective: Coarse-grained models for biomolecular systems.
AB  - By focusing on essential features, while averaging over less important details,
      coarse-grained (CG) models provide significant computational and conceptual
      advantages with respect to more detailed models. Consequently, despite dramatic
      advances in computational methodologies and resources, CG models enjoy surging
      popularity and are becoming increasingly equal partners to atomically detailed
      models. This perspective surveys the rapidly developing landscape of CG models
      for biomolecular systems. In particular, this review seeks to provide a balanced,
      coherent, and unified presentation of several distinct approaches for developing
      CG models, including top-down, network-based, native-centric, knowledge-based,
      and bottom-up modeling strategies. The review summarizes their basic
      philosophies, theoretical foundations, typical applications, and recent
      developments. Additionally, the review identifies fundamental inter-relationships
      among the diverse approaches and discusses outstanding challenges in the field.
      When carefully applied and assessed, current CG models provide highly efficient
      means for investigating the biological consequences of basic physicochemical
      principles. Moreover, rigorous bottom-up approaches hold great promise for
      further improving the accuracy and scope of CG models for biomolecular systems. 

PMID- 24028091
TI  - The relationship between socially-assigned ethnicity, health and experience of
      racial discrimination for Maori: analysis of the 2006/07 New Zealand Health
      Survey.
AB  - BACKGROUND: In New Zealand, there are significant and long-standing inequalities
      in a range of health outcomes, risk factors and healthcare measures between Maori
      (indigenous peoples) and Pakeha (European). This study expands our understanding
      of racism as a determinant of such inequalities to examine the concept of
      socially-assigned ethnicity (how an individual is classified by others
      ethnically/racially) and its relationship to health and racism for Maori. There
      is some evidence internationally that being socially-assigned as the dominant
      ethnic group (in this case European) offers health advantage. METHODS: We
      analysed data from the 2006/07 New Zealand Health Survey for adult participants
      who self-identified their ethnicity as Maori (n = 3160). The association between
      socially-assigned ethnicity and individual experience of racial discrimination,
      and socially-assigned ethnicity and health (self-rated health, psychological
      distress [Kessler 10-item scale]) was assessed using logistic and linear
      regression analyses, respectively. RESULTS: Maori who were socially-assigned as
      European-only had significantly lower experience of racial discrimination
      (adjusted odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.44, 0.78) than
      Maori who were socially-assigned as non-European. Being socially-assigned as
      European-only was also associated with health advantage compared to being
      socially-assigned non-European: more likely to respond with self-rated very
      good/excellent health (age, sex adjusted OR = 1.39, 95% CI = 1.10, 1.74), and
      lower Kessler 10 scores (age, sex adjusted mean difference = -0.66, 95% C I = 
      1.22, -0.10). These results were attenuated following adjustment for
      socioeconomic measures and experience of racial discrimination. CONCLUSIONS:
      Results suggest that, in a race conscious society, the way people's ethnicities
      are viewed by others is associated with tangible health risk or advantage, and
      this is consistent with an understanding of racism as a health determinant.

PMID- 24028093
TI  - Communication: Determining the lowest-energy isomer of Au8: 2D, or not 2D.
AB  - A parallel numerical derivative code, combined with parallel implementation of
      the coupled-cluster method with singles, doubles, and non-iterative triples
      (CCSD(T)), is used to optimize the geometries of the low-energy structures of the
      Au8 particle. The effects of geometry relaxation at the CCSD(T) level and the
      combined effects of the basis set and core-valence correlations are examined and
      the results are compared with the corresponding second-order Moller-Plesset
      perturbation theory calculations. The highest-level computations, in which the
      single-point CCSD(T) calculations employing the correlation-consistent basis set
      of the cc-pVTZ quality and the associated relativistic effective core potential
      (ECP), both optimized for gold, and correlating the 5d(10)6s(1) valence and
      5s(2)5p(6) semi-core electrons, are combined with the geometrical information
      obtained with the corresponding CCSD(T)/cc-pVDZ/ECP approach, favor the planar
      configuration, with the next three non-planar structures separated by 4-6
      kcal/mol. In agreement with the earlier work, smaller-basis set CCSD(T)
      computations provide unreliable results for the relative energetics, even when
      the geometries are optimized at the CCSD(T) level.

PMID- 24028094
TI  - Communication: Long-lived states of nuclear spins in solids.
AB  - We report an observation of extremely long-lived spin states in systems of
      dipolar-coupled nuclear spins in solids. The "suspended echo" experiment uses a
      simple stimulated echo pulse sequence and creates non-equilibrium states which
      live many orders of magnitude longer than the characteristic time of spin-spin
      dynamics T2. Large amounts of information can be encoded in such long-lived
      states and subsequently retrieved by an application of a single "reading" pulse. 

PMID- 24028095
TI  - Communication: Evidence of structural phase transitions in silicalite-1 by
      infrared spectroscopy.
AB  - The adsorption of trichloroethylene, perchloroethylene, and p-xylene on a MFI
      (Mobile-FIve) zeolite is studied using in situ FTIR spectroscopy at 298 K.
      Spectra of self-supported zeolites in contact with increasing pressures of pure
      gas were recorded at equilibrium in the mid-infrared domain. Analysis of the
      evolution of the shape and location of vibrational bands of the zeolite as a
      function of the amount adsorbed allowed the observation of structural
      modifications of the adsorbent for the first time by infrared spectroscopy. 

PMID- 24028096
TI  - Barrierless electronic relaxation in solution: An analytically solvable model.
AB  - We propose an analytical method for understanding the problem of electronic
      relaxation in solution, modelled by a particle undergoing diffusive motion under
      the influence of two potentials. The coupling between the two potentials is
      assumed to be represented by a Dirac delta function. The diffusive motion in this
      paper is described by the Smoluchowski equation. Our solution requires the
      knowledge of the Laplace transform of the Green's function for the motion in both
      the uncoupled potentials. Our model is more general than all the earlier models,
      because we are the first one to consider the effect of ground state potential
      energy surface explicitly. 

PMID- 24028097
TI  - Electronic density response to molecular geometric changes from explicit
      electronic susceptibility calculations.
AB  - We present a first principles approach to compute the response of the molecular
      electronic charge distribution to a geometric distortion. The scheme is based on
      an explicit representation of the linear electronic susceptibility. The linear
      electronic susceptibility is a tensor quantity which directly links the first
      order electronic response density to the perturbation potential, without
      requiring self-consistency. We first show that the electronic susceptibility is
      almost invariant to small changes in the molecular geometry. We then compute the
      dipole moments from the response density induced by the geometrical changes. We
      verify the accuracy by comparing the results to the corresponding values obtained
      from the self-consistent calculations of the ground-state densities in both
      geometries. 

PMID- 24028098
TI  - Photoionization cross section by Stieltjes imaging applied to coupled cluster
      Lanczos pseudo-spectra.
AB  - A recently implemented asymmetric Lanczos algorithm for computing (complex)
      linear response functions within the coupled cluster singles (CCS), coupled
      cluster singles and iterative approximate doubles (CC2), and coupled cluster
      singles and doubles (CCSD) is coupled to a Stieltjes imaging technique in order
      to describe the photoionization cross section of atoms and molecules, in the
      spirit of a similar procedure recently proposed by Averbukh and co-workers within
      the Algebraic Diagrammatic Construction approach. Pilot results are reported for
      the atoms He, Ne, and Ar and for the molecules H2, H2O, NH3, HF, CO, and CO2. 

PMID- 24028099
TI  - Perturbed atoms in molecules and solids: The PATMOS model.
AB  - A new computational method for electronic-structure studies of molecules and
      solids is presented. The key element in the new model - denoted the perturbed
      atoms in molecules and solids model - is the concept of a perturbed atom in a
      complex. The basic approximation of the new model is unrestricted Hartree Fock
      (UHF). The UHF orbitals are localized by the Edmiston-Ruedenberg procedure. The
      perturbed atoms are defined by distributing the orbitals among the nuclei in such
      a way that the sum of the intra-atomic UHF energies has a minimum. Energy
      corrections with respect to the UHF energy, are calculated within the energy
      incremental scheme. The most important three- and four-electron corrections are
      selected by introducing a modified geminal approach. Test calculations are
      performed on N2, Li2, and parallel arrays of hydrogen atoms. The character of the
      perturbed atoms is illustrated by calculations on H2, CH4, and C6H6. 

PMID- 24028100
TI  - An efficient linear-scaling CCSD(T) method based on local natural orbitals.
AB  - An improved version of our general-order local coupled-cluster (CC) approach [Z.
      Rolik and M. Kallay, J. Chem. Phys. 135, 104111 (2011)] and its efficient
      implementation at the CC singles and doubles with perturbative triples [CCSD(T)]
      level is presented. The method combines the cluster-in-molecule approach of Li
      and co-workers [J. Chem. Phys. 131, 114109 (2009)] with frozen natural orbital
      (NO) techniques. To break down the unfavorable fifth-power scaling of our
      original approach a two-level domain construction algorithm has been developed.
      First, an extended domain of localized molecular orbitals (LMOs) is assembled
      based on the spatial distance of the orbitals. The necessary integrals are
      evaluated and transformed in these domains invoking the density fitting
      approximation. In the second step, for each occupied LMO of the extended domain a
      local subspace of occupied and virtual orbitals is constructed including
      approximate second-order Moller-Plesset NOs. The CC equations are solved and the
      perturbative corrections are calculated in the local subspace for each occupied
      LMO using a highly-efficient CCSD(T) code, which was optimized for the typical
      sizes of the local subspaces. The total correlation energy is evaluated as the
      sum of the individual contributions. The computation time of our approach scales
      linearly with the system size, while its memory and disk space requirements are
      independent thereof. Test calculations demonstrate that currently our method is
      one of the most efficient local CCSD(T) approaches and can be routinely applied
      to molecules of up to 100 atoms with reasonable basis sets. 

PMID- 24028102
TI  - A test of systematic coarse-graining of molecular dynamics simulations: Transport
      properties.
AB  - To what extent can a "bottom-up" mesoscale fluid model developed through
      systematic coarse-graining techniques recover the physical properties of a
      molecular scale system? In a previous paper [C.-C. Fu, P. M. Kulkarni, M. S.
      Shell, and L. G. Leal, J. Chem. Phys. 137, 164106 (2012)], we addressed this
      question for thermodynamic properties through the development of coarse-grained
      (CG) fluid models using modified iterative Boltzmann inversion methods that
      reproduce correct pair structure and pressure. In the present work we focus on
      the dynamic behavior. Unlike the radial distribution function and the pressure,
      dynamical properties such as the self-diffusion coefficient and viscosity in a CG
      model cannot be matched during coarse-graining by modifying the pair interaction.
      Instead, removed degrees of freedom require a modification of the equations of
      motion to simulate their implicit effects on dynamics. A simple but approximate
      approach is to introduce a friction coefficient, gamma, and random forces for the
      remaining degrees of freedom, in which case gamma becomes an additional parameter
      in the coarse-grained model that can be tuned. We consider the non-Galilean
      invariant Langevin and the Galilean-invariant dissipative particle dynamics (DPD)
      thermostats with CG systems in which we can systematically tune the fraction phi
      of removed degrees of freedom. Between these two choices, only DPD allows both
      the viscosity and diffusivity to match a reference Lennard-Jones liquid with a
      single value of gamma for each degree of coarse-graining phi. This friction
      constant is robust to the pressure correction imposed on the effective CG
      potential, increases approximately linearly with phi, and also depends on the
      interaction cutoff length, rcut, of the pair interaction potential. Importantly,
      we show that the diffusion constant and viscosity are constrained by a simple
      scaling law that leads to a specific choice of DPD friction coefficient for a
      given degree of coarse-graining. Moreover, we find that the pair interaction
      distance cutoffs used for DPD random and dissipative forces should be considered
      separately from that of the conservative interaction potential. 

PMID- 24028101
TI  - Electrostatic forces in the Poisson-Boltzmann systems.
AB  - Continuum modeling of electrostatic interactions based upon numerical solutions
      of the Poisson-Boltzmann equation has been widely used in structural and
      functional analyses of biomolecules. A limitation of the numerical strategies is
      that it is conceptually difficult to incorporate these types of models into
      molecular mechanics simulations, mainly because of the issue in assigning atomic
      forces. In this theoretical study, we first derived the Maxwell stress tensor for
      molecular systems obeying the full nonlinear Poisson-Boltzmann equation. We
      further derived formulations of analytical electrostatic forces given the Maxwell
      stress tensor and discussed the relations of the formulations with those
      published in the literature. We showed that the formulations derived from the
      Maxwell stress tensor require a weaker condition for its validity, applicable to
      nonlinear Poisson-Boltzmann systems with a finite number of singularities such as
      atomic point charges and the existence of discontinuous dielectric as in the
      widely used classical piece-wise constant dielectric models. 

PMID- 24028103
TI  - An effective method for state population within time-dependent density functional
      theory.
AB  - The determination of state population probability within the framework of time
      dependent density functional theory (TDDFT) has remained a widely open question.
      The aim of this study is to find out whether and how this probability can be
      extracted from time-dependent density, which has been used as the basic variable
      within TDDFT. We propose an effective method to calculate state population
      probabilities, which has been well validated in benchmark case studies on
      nonresonant (detuned) Rabi oscillations of a Na atom, Na2 dimer, and Na4 cluster
      irradiated by a monochromatic laser. 

PMID- 24028104
TI  - Reduced purities as measures of decoherence in many-electron systems.
AB  - A hierarchy of measures of decoherence for many-electron systems that is based on
      the purity and the hierarchy of reduced electronic density matrices is presented.
      These reduced purities can be used to characterize electronic decoherence in the
      common case when the many-body electronic density matrix is not known and only
      reduced information about the electronic subsystem is available. Being defined
      from reduced electronic quantities, the interpretation of the reduced purities is
      more intricate than the usual (many-body) purity. This is because the
      nonidempotency of the r-body reduced electronic density matrix that is the basis
      of the reduced purity measures can arise due to decoherence or due to electronic
      correlations. To guide the interpretation, explicit expressions are provided for
      the one-body and two-body reduced purities for a general electronic state. Using
      them, the information content and structure of the one-body and two-body reduced
      purities is established, and limits on the changes that decoherence can induce
      are elucidated. The practical use of the reduced purities to understand
      decoherence dynamics in many-electron systems is exemplified through an analysis
      of the electronic decoherence dynamics in a model molecular system. 

PMID- 24028105
TI  - Ewald summation on a helix: A route to self-consistent charge density-functional
      based tight-binding objective molecular dynamics.
AB  - We explore the generalization to the helical case of the classical Ewald method,
      the harbinger of all modern self-consistent treatments of waves in crystals,
      including ab initio electronic structure methods. Ewald-like formulas that do not
      rely on a unit cell with translational symmetry prove to be numerically tractable
      and able to provide the crucial component needed for coupling objective molecular
      dynamics with the self-consistent charge density-functional based tight-binding
      treatment of the inter-atomic interactions. The robustness of the method in
      addressing complex hetero-nuclear nano- and bio-systems is demonstrated with
      illustrative simulations on a helical boron nitride nanotube, a screw dislocated
      zinc oxide nanowire, and an ideal DNA molecule. 

PMID- 24028106
TI  - Robust fitting techniques in the chain of spheres approximation to the Fock
      exchange: The role of the complementary space.
AB  - The chain of spheres seminumerical integration algorithm is reexamined from the
      point of view of various numerical error cancellation schemes. The two sources of
      ideas are the robust fitting technique of Dunlap and the dealiasing concept of
      the pseudospectral methods of Friesner. The most efficient scheme is identified
      and is found to be a generalization of the overlap fitting procedure discussed
      earlier. It will be shown that due to the conceptual similarity between
      complementary auxiliary basis functions of explicitly correlated approaches and
      the dealiasing functions of pseudospectral methods, the former can be used in a
      similar manner as the latter to cancel numerical errors. In contrast to the
      dealiasing functions, the complementary auxiliary basis functions are not
      specific to the integration grid. The scheme obtained can dramatically improve
      reaction energies even using small grid setups at a moderate additional cost. 

PMID- 24028107
TI  - Breit interaction effects in relativistic theory of the nuclear spin-rotation
      tensor.
AB  - In this work, relativistic effects on the nuclear spin-rotation (SR) tensor
      originated in the electron-nucleus and electron-electron Breit interactions are
      analysed. To this end, four-component numerical calculations were carried out in
      model systems HX (X=H,F,Cl,Br,I). The electron-nucleus Breit interaction couples
      the electrons and nuclei dynamics giving rise to a purely relativistic
      contribution to the SR tensor. Its leading order in 1/c is of the same value as
      that of relativistic corrections on the usual second order expression of the SR
      tensor considered in previous work [I. A. Aucar, S. S. Gomez, J. I. Melo, C. G.
      Giribet, and M. C. Ruiz de Azua, J. Chem. Phys. 138, 134107 (2013)], and
      therefore it is absolutely necessary to establish its relative importance. For
      the sake of completeness, the corresponding effect originating in the electron
      electron Breit interaction is also considered. It is verified that in all cases
      these Breit interactions yield only very small corrections to the SR tensors of
      both the X and H nuclei in the present series of compounds. Results of the
      present work strongly suggest that in order to achieve experimental accuracy in
      the theoretical study of the SR tensor both electron-nucleus and electron
      electron Breit effects can be safely neglected. 

PMID- 24028108
TI  - Trimer effects in fragment molecular orbital-linear combination of molecular
      orbitals calculation of one-electron orbitals for biomolecules.
AB  - The fragment molecular orbital (FMO)-linear combination of molecular orbitals
      (LCMO) method incorporates as an efficient post-process calculation of one
      electron orbitals of the whole system after the FMO total energy calculation. A
      straightforward way to increase the accuracy is inclusion of the trimer effect.
      Here, we derive a comprehensive formulation called the FMO3-LCMO method. To keep
      the computational costs of the trimer term low enough, we use a matrix-size
      reduction technique. We evaluated the accuracy and efficiency of the FMO3-LCMO
      scheme in model biological systems (alanine oligomer and chignolin). The results
      show that delocalized electronic orbitals with covalent and hydrogen bonds are
      better described at the trimer level, and the FMO3-LCMO method is applicable to
      quantitative evaluations of a wide range of frontier orbitals in large
      biosystems. 

PMID- 24028109
TI  - Solid-liquid coexistence in small systems: A statistical method to calculate
      melting temperatures.
AB  - We propose an efficient and accurate scheme to calculate the melting point (MP)
      of materials. This method is based on the statistical analysis of small-size
      coexistence molecular dynamics simulations. It eliminates the risk of metastable
      superheated solid in the fast-heating method, while also significantly reducing
      the computer cost relative to the traditional large-scale coexistence method.
      Using empirical potentials, we validate the method and systematically study the
      finite-size effect on the calculated MPs. The method converges to the exact
      result in the limit of large system size. An accuracy within 100 K in MP is
      usually achieved when simulation contains more than 100 atoms. Density functional
      theory examples of tantalum, high-pressure sodium, and ionic material NaCl are
      shown to demonstrate the accuracy and flexibility of the method in its practical
      applications. The method serves as a promising approach for large-scale automated
      material screening in which the MP is a design criterion. 

PMID- 24028110
TI  - Kinetic measurements of the C2H5O2 radical using time-resolved cavity ring-down
      spectroscopy with a continuous source.
AB  - We report on the design of a time-resolved, high duty-factor cavity ring-down
      apparatus utilizing a continuous laser and detail a technique for the accurate
      and precise measurement of effective reaction rate constants with it. This report
      complements an earlier paper concerning the measurement of the absolute
      absorption cross-sections, sigmaP, of reactive intermediates. To demonstrate the
      performance of the new technique, we have measured the decay rate of ethyl peroxy
      radicals by monitoring the A<-X origin band of the G-conformer of these species.
      A measured value kobs/sigmaP = 1.827(45) * 10(7) cm/s was determined and it,
      along with the previously measured value of sigmaP, was used to derive the value
      of kobs = 9.66(44)*10(-14) cm(3)/s, for the effective rate constant for ethyl
      peroxy self-reaction (all uncertainties are 1 sigma). The present value of kobs
      is compared to those previously reported, and sources of systematic errors and
      their impact are discussed. 

PMID- 24028111
TI  - Force-field calculation and geometry of the HOOO radical.
AB  - High-level ab initio calculations using the Davidson-corrected multireference
      configuration interaction (MRCI) level of theory with Dunning's correlation
      consistent basis sets and force-field calculations were performed for the HOOO
      radical. The harmonic vibrational frequencies and their anharmonic constants
      obtained by the force-field calculations reproduce the IR-UV experimental
      vibrational frequencies with errors less than 19 cm(-1). The rotational constants
      for the ground vibrational state obtained using the vibration-rotation
      interaction constants of the force-field calculations also reproduce the
      experimentally determined rotational constants with errors less than 0.9%,
      indicating that the present quantum chemical calculations and the derived
      spectroscopic constants have high accuracy. The equilibrium structure was
      determined from the experimentally determined rotational constants combined with
      the theoretically derived vibration-rotation interaction constants. The
      determined geometrical parameters agree well with the results of the present MRCI
      calculation. 

PMID- 24028112
TI  - Explicitly correlated composite thermochemistry of transition metal species.
AB  - Atomization energies were calculated using explicitly correlated coupled cluster
      methods with correlation consistent basis sets for a series of 19 small molecules
      containing 3d transition metal atoms. The atomization energies were calculated
      using a modified Feller-Peterson-Dixon approach in which CCSD(T) complete basis
      set (CBS) limits were obtained using extrapolations of aVTZ/aVQZ CCSD(T)-F12b
      correlation energies, and then a series of additive contributions for relativity,
      core correlation, higher order correlation, and zero-point vibrations were
      included. The frozen-core CBS limits calculated with F12 methods closely matched
      the more computational expensive conventional awCVQZ/awCV5Z CBS extrapolations,
      with a mean unsigned deviation of just 0.1 kcal/mol. In particular, the CCSD(T*)
      F12b/aVDZ and aVTZ atomization energies were more accurate on average than the
      conventional CCSD(T)/aVQZ and aV5Z results, respectively. In several cases the
      effects of higher order correlation beyond CCSD(T), as judged by CCSDT and
      CCSDT(Q)Lambda calculations, were greater than 1 kcal/mol, reaching 4.5 kcal/mol
      for CrO3. For the 16 molecules of this study with experimental uncertainties of
      ~3.5 kcal/mol or less, the final composite heats of formation have a mean
      unsigned deviation (MUD) from experiment of just 1.3 kcal/mol, which is slightly
      smaller than the average of the experimental uncertainties, 1.8 kcal/mol. The
      root mean square deviation (RMS) is only slightly larger at 1.7 kcal/mol. Without
      the contributions due to higher order correlation effects, the MUD and RMS rise
      to 2.1 and 2.8 kcal/mol, respectively. To facilitate the F12 calculations, new
      (aug-)cc-pVnZ/MP2Fit (n = Q, 5) and (aug-)cc-pwCVTZ/MP2Fit auxiliary basis sets
      were also developed for the transition metal atoms. 

PMID- 24028114
TI  - Excited electronic states and spectroscopy of unsymmetrically substituted
      polyenes.
AB  - alpha-Methyl-omega-phenylpolyenes, Me-(CH=CH)N-Ph, (MPPNs) with N = 2, 3, and 4
      were synthesized. Fluorescence, absorption, and excitation spectra of MPPNs have
      been measured under different conditions along with those of beta-methylstyrene.
      It is shown that there is a forbidden singlet (pi, pi*) excited state located at
      energies below the absorbing state for MPPNs with N = 3 and 4. Excitation
      energies of these polyenes are determined as a function of N. Quantitative
      analysis of the temperature dependence of the relative intensity of the
      fluorescence spectrum and its solvent shift behavior extract estimates of the
      various physical parameters that characterize excitation energies and excited
      state dynamical behavior of MPPN with N = 3. The singlet excited states of the
      MPPNs were compared with those of the alpha,omega-diphenylpolyenes and
      alpha,omega-dimethylpolyenes. 

PMID- 24028113
TI  - Conical-intersection quantum dynamics of OH(A2Sigma+) + H(2S) collisions.
AB  - We present the conical-intersection quantum dynamics of the nonreactive quenching
      (NQ) OH(A(2)Sigma(+)) + H'((2)S) -> OH(X(2)Pi) + H'((2)S), exchange (X)
      OH(A(2)Sigma(+)) + H'((2)S) -> OH'(A(2)Sigma(+)) + H((2)S), exchange-quenching
      (XQ) OH(A(2)Sigma(+)) + H'((2)S) -> OH'(X(2)Pi) + H((2)S), and reaction (R)
      OH(A(2)Sigma(+)) + H'((2)S) -> O((1)D) + H2(X(1)Sigmag (+)) collisions. We obtain
      initial-state-resolved reaction probabilities, cross sections, and rate constants
      by considering OH in the ground vibrational state and in the rotational levels j0
      = 0, 1, 2, and 5. Coupled-channel real wavepackets (WPs) on the X(1)A(') and
      B(1)A(') coupled electronic states are propagated by using the Dobbyn and Knowles
      diabatic potential surfaces and coupling [A. J. Dobbyn and P. J. Knowles, Mol.
      Phys. 91, 1107 (1997) and A. J. Dobbyn and P. J. Knowles, Faraday Discuss. 110,
      207 (1998)], and performing asymptotic or flux analysis. NQ is the preferred
      product channel, followed by XQ, R, and X. Moreover, the nonadiabatic quenching
      processes account for more than 80% of the total rate constants. WP snapshots
      show a reaction mechanism in good agreement with reaction probabilities. NQ, XQ,
      and R cross sections, and NQ rate constants decrease with the collision energy
      and j0, whereas the X reactivity increases, and XQ and R rates are nearly
      constant with j0. In general, quantum rate constants are smaller than
      experimental or quasiclassical data. 

PMID- 24028115
TI  - Structures and optical absorptions of PbSe clusters from ab initio calculations.
AB  - Based on the low-lying structures of (PbSe)n (n = 1-10) clusters identified with
      a first-principles molecular dynamics approach, two growth patterns with distinct
      structure and energy evolutions were predicted for the even-n and odd-n clusters,
      respectively. Moreover, the clusters favor a simple cubic and bulk-like growth
      pattern, unlike the extensively studied II-VI clusters whose structural diversity
      has been well established. The overlap between 6p of Pb and 4p of Se makes not
      only the ordered and bulk-like structures but also a stable building block of
      (PbSe)4. The high stability of (PbSe)4 is recognized in terms of its binding
      energy, HOMO-LUMO gap, appearance in the structures of larger-size clusters, as
      well as its appearance in the fragmentation products of PbSe clusters. The
      geometrical and electronic structures of the PbSe clusters were further studied
      within the density functional theory framework including spin-orbital (SO)
      coupling. We found that SO coupling does not change the relative stability of the
      clusters but reduces their binding energy significantly. Particularly, the SO
      effect has a great impact on the UV-vis spectra of the clusters, which were
      simulated with time-dependent density functional theory at SO level of zeroth
      order regular approximation. 

PMID- 24028116
TI  - Structure of Au4(0/-1) in the gas phase: A joint geometry relaxed ab initio
      calculations and vibrationally resolved photoelectron imaging investigation.
AB  - We have combined photoelectron velocity-map imaging spectroscopy and high-level
      ab initio calculations to elucidate the geometries of Au4 (0/-1). Well-resolved
      ground-state electronic transition was observed in the photoelectron spectrum of
      Au4 (-) at 446 nm, leading to more accurate electron affinity and vibrational
      frequencies for the ground state of the neutral Au4 (-). The pure and
      vibrationally resolved spectra provide definitive experimental evidence for the
      resolution of the ground-state gold tetramer in the gaseous phase, with the aid
      of the ab initio calculations and Franck-Condon simulations. The comprehensive
      comparisons between the experiment and theoretical calculations suggest that the
      Y-shaped structure is the global minimum for both the neutral and anionic Au4.

PMID- 24028117
TI  - Quasiclassical dynamics for the H + HS abstraction and exchange reactions on the
      3A" and the 3A' states.
AB  - A detailed quasiclassical trajectory study of the H + HS reaction yielding an
      exchange (H + HS) and an abstraction (H2 + S) channel has been performed by
      employing the new triplet (3)A" and (3)A' surfaces developed by our group. The
      cross sections for both channels are presented and found to be in good agreement
      with previous quantum wave packet results. The thermal rate coefficients for
      abstraction channel at the temperature between 200 and 1000 K have been evaluated
      by averaging over a Boltzmann distribution of rotational states and compared with
      the available experimental values. It is found that the thermal rate coefficients
      exhibit a conventional Arrhenius-type dependence on temperature, which agrees
      well with the experimental data. Average fractions, vibration and rotation
      distributions of the products H2 and HS at different collision energies have been
      also fully investigated. Furthermore, influence of the collision energy on the
      total and product-state-resolved differential cross sections (DCSs) for both
      channels are calculated and discussed. Some observations on the mechanism of the
      title reaction have been made; in particular it was discovered that reactive
      collisions along the collinear pathway cause the H2 product to scatter backward,
      while the reactive collisions with large impact parameters b, which are favored
      deviating from the minimum energy path, produced mainly forward scattering. For
      the exchange channel, the discrepancies in the DCS are also distinguished through
      an analysis of individual trajectories and found a double microscopic mechanism,
      migration or non-migration. The state-to-state DCSs provide a global perspective
      of the reaction mechanisms and their contribution to the final product internal
      energy states. The theoretical findings are discussed and compared with a
      kinematic constraint model. 

PMID- 24028118
TI  - Rotationally resolved B<-X electronic spectra of the isopropoxy radical: A
      comparative study.
AB  - The B-X laser-induced-fluorescence spectrum of jet-cooled isopropoxy radical (i
      C3H7O[middle dot]) has been recorded. Using an isolated state model the observed
      rotational and fine structure of the origin band has been well simulated to
      determine rotational constants for both the X and B states and the electron spin
      rotation constants of the X state. The line intensities are well simulated with a
      parallel transition type, requiring the same symmetry for the levels involved of
      each the X and B state, which confirms the previous suggestion that going from
      ethoxy (C2H5O[middle dot]) to isopropoxy, the energy ordering of the electron
      configurations with in- and out-of-plane half-filled p-orbitals of the oxygen
      atom is reversed and the ground vibronic symmetry changes from a" to a'. However,
      the observed spin-rotation coupling constants are not consistent with their
      predication from either semi-empirical theory or quantum chemical calculations.
      Additionally, the lack of observed transitions involving the out-of-plane
      transition moment component is not consistent with high level electronic
      structure calculations suggesting mixing of vibronic levels by strong spin-orbit
      coupling. A new twofold model has been developed that explicitly includes
      Coriolis and spin-orbit coupling between different vibronic levels. This model
      renders the discrepancy between theoretical and experimental spin-rotation
      constants moot. Moreover, it determines independently the contributions to the
      observed splitting between the lowest two levels, resulting from non-relativistic
      kinetic and Coulombic effects, and that due to the relativistic spin-orbit
      interaction. The experimental values show that these effects are comparable, but
      that the vibronic one is slightly more important. This result is at variance with
      state-of-the-art electronic structure calculations which otherwise do a
      remarkably good job of describing the ground state of isopropoxy. 

PMID- 24028119
TI  - How a single aluminum atom makes a difference to gallium: First-principles
      simulations of bimetallic cluster melting.
AB  - First principles molecular dynamics simulations of Ga19Al(+) have been performed
      in the microcanonical ensemble using parallel tempering. We perform a thorough
      investigation of the changes induced by the presence of an Al atom in the Ga
      dominated cluster. Dynamic analysis indicates that the Al atom prefers to occupy
      the internal sites of the cluster structure, at all temperatures, and above 450
      K, the Al atom is less mobile than the central Ga atom throughout the simulation.
      Using the multiple histogram method, canonical specific heat curves are obtained
      that compare well with previous experimental measurements of the specific heat
      and equivalent simulations for the Ga20 (+) cluster. The first-principles melting
      temperature agrees well with the experimental value for Ga19Al(+). Analysis of
      the root mean squared fluctuation in bond length, velocity auto-correlation
      function, and the corresponding power spectrum, confirms the solid-liquid-like
      phase transition in Ga19Al(+), as for Ga20 (+). 

PMID- 24028120
TI  - Supramolecular step in design of nonlinear optical materials: Effect of pi...pi
      stacking aggregation on hyperpolarizability.
AB  - Theoretical estimation of nonlinear optical (NLO) properties is an important step
      in systematic search for optoelectronic materials. Density functional theory
      methods are often used to predict first molecular hyperpolarizability for
      compounds in advance of their synthesis. However, design of molecular NLO
      materials require an estimation of the bulk properties, which are often
      approximated as additive superposition of molecular tensors. It is therefore
      important to evaluate the accuracy of this additive approximation and estimate
      the extent by which intermolecular interactions influence the first molecular
      hyperpolarizability beta. Here we focused on the stacking aggregates, including
      up to 12 model molecules (pNA and ANS) and observed enhancement and suppression
      of molecular hyperpolarizability relative to the additive sum. We found that
      degree of nonadditivity depends on relative orientation of the molecular dipole
      moments and does not correlate with intermolecular interaction energy. Frenkel
      exciton model, based on dipole-dipole approximation can be used for qualitative
      prediction of intermolecular effects. We report on inaccuracy of this model for
      the molecules with long pi-systems that are significantly shifted relative to
      each other, when dipole-dipole approximation becomes inaccurate. To obtain more
      detailed information on the effect of intermolecular interactions on beta we
      proposed electrostatic approach which accounts for the mutual polarization of the
      molecules by each other. We measure the induced polarization of each molecule in
      the aggregate by the charge of its donor (or acceptor) group. The proposed
      approach demonstrates linear correlation beta(FF) vs beta(elm) (estimated by
      finite field theory and electrostatic model, respectively) and allows
      decomposition of the hyperpolarizability for a molecular aggregate into separate
      molecular contributions. We used this decomposition to analyze the reasons of
      deviation of aggregate beta from additivity, as well as the cooperative effect of
      intermolecular interactions on hyperpolarizability for stacks of growing size. In
      cases of positive cooperativity (enhancement), we found 6-8 molecules to be
      necessary to reach the asymptotic limit. In more frequent cases of negative
      cooperativity two opposite factors play role. The first one consists of direct
      lowering of beta due to repulsive dipole-dipole interactions. The second factor
      is originated in a decrease of molecular dipole moments, which in turn leads to a
      decrease of dipole-dipole repulsion, and therefore increases beta. For strong
      intermolecular repulsive dipole-dipole interactions these effects nearly cancel
      each other. In such cases the trimers and even dimers are sufficient to reach the
      asymptotic limit of the infinite stacks. Based on the observed trends we
      estimated non-additive correction to beta for well known NLO crystals NPAN and
      MNMA. In the case of NPAN, stacking effect on molecular hyperpolarizability
      represents the leading component of the crystal packing effect and improves the
      agreement between calculated and experimental data which is further improved when
      frequency dependence is taken in account. 

PMID- 24028121
TI  - Improved coarse-grained model for molecular-dynamics simulations of water
      nucleation.
AB  - We developed a new coarse-grained (CG) model for water to study nucleation of
      droplets from the vapor phase. The resulting potential has a more flexible
      functional form and a longer range cutoff compared to other CG potentials
      available for water. This allowed us to extend the range of applicability of
      coarse-grained techniques to nucleation phenomena. By improving the description
      of the interactions between water molecules in the gas phase, we obtained CG
      model that gives similar results than the all-atom (AA) TIP4P model but at a
      lower computational cost. In this work we present the validation of the potential
      and its application to the study of nucleation of water droplets from the
      supersaturated vapor phase via molecular-dynamics simulations. The computed
      nucleation rates at T = 320 K and 350 K at different supersaturations, ranging
      from 5 to 15, compare very well with AA TIP4P simulations and show the right
      dependence on the temperature compared with available experimental data. To help
      comparison with the experiments, we explored in detail the different ways to
      control the temperature and the effects on nucleation. 

PMID- 24028122
TI  - Isotropic magnetic shielding constants of retinal derivatives in aprotic and
      protic solvents.
AB  - We investigate the nuclear isotropic shielding constants sigma((13)C) and
      sigma((17)O) of isomers of retinoic acid and retinal in gas-phase and in
      chloroform, acetonitrile, methanol, and water solutions via Monte Carlo
      simulation and quantum mechanics calculations using the GIAO-B3LYP/6
      311++G(2d,2p) approach. Electronic solute polarization effects due to protic and
      aprotic solvents are included iteratively and play an important role in the
      quantitative determination of oxygen shielding constants. Our MP2/6-31G+(d)
      results show substantial increases of the dipole moment of both retinal
      derivatives in solution as compared with the gas-phase results (between 22% and
      26% in chloroform and between 55% and 99% in water). For the oxygen atoms the
      influence of the solute polarization is mild for sigma((17)O) of hydroxyl group,
      even in protic solvents, but it is particularly important for sigma((17)O) of
      carbonyl group. For the latter, there is a sizable increase in the magnitude with
      increasing solvent polarity. For the carbon atoms, the solvent effects on the
      sigma((13)C) values are in general small, being more appreciable in carbon atoms
      of the polyene chain than in the carbon atoms of the beta-ionone ring and methyl
      groups. The results also show that isomeric changes on the backbones of the
      polyene chains have marked influence on the (13)C chemical shifts of carbon atoms
      near to the structural distortions, in good agreement with the experimental
      results measured in solution. 

PMID- 24028123
TI  - Solvent dependence of Stokes shift for organic solute-solvent systems: A
      comparative study by spectroscopy and reference interaction-site model-self
      consistent-field theory.
AB  - The Stokes shift magnitudes for coumarin 153 (C153) in 13 organic solvents with
      various polarities have been determined by means of steady-state spectroscopy and
      reference interaction-site model-self-consistent-field (RISM-SCF) theory. RISM
      SCF calculations have reproduced experimental results fairly well, including
      individual solvent characteristics. It is empirically known that in some
      solvents, larger Stokes shift magnitudes are detected than anticipated on the
      basis of the solvent relative permittivity, Er. In practice, 1,4-dioxane (Er =
      2.21) provides almost identical Stokes shift magnitudes to that of
      tetrahydrofuran (THF, Er = 7.58), for C153 and other typical organic solutes. In
      this work, RISM-SCF theory has been used to estimate the energetics of C153
      solvent systems involved in the absorption and fluorescence processes. The Stokes
      shift magnitudes estimated by RISM-SCF theory are ~5 kJ mol(-1) (400 cm(-1)) less
      than those determined by spectroscopy; however, the results obtained are still
      adequate for dipole moment comparisons, in a qualitative sense. We have also
      calculated the solute-solvent site-site radial distributions by this theory. It
      is shown that solvation structures with respect to the C-O-C framework, which is
      common to dioxane and THF, in the near vicinity (~0.4 nm) of specific solute
      sites can largely account for their similar Stokes shift magnitudes. In previous
      works, such solute-solvent short-range interactions have been explained in terms
      of the higher-order multipole moments of the solvents. Our present study shows
      that along with the short-range interactions that contribute most significantly
      to the energetics, long-range electrostatic interactions are also important. Such
      long-range interactions are effective up to 2 nm from the solute site, as in the
      case of a typical polar solvent, acetonitrile. 

PMID- 24028124
TI  - Molecular dynamics study of CO2 hydrate dissociation: Fluctuation-dissipation and
      non-equilibrium analysis.
AB  - Equilibrium and non-equilibrium molecular dynamics (MD) simulations have been
      performed to investigate thermal-driven break-up of planar CO2 hydrate interfaces
      in liquid water at 300-320 K. Different guest compositions, at 85%, 95%, and 100%
      of maximum theoretical occupation, led to statistically-significant differences
      in the observed initial dissociation rates. The melting temperatures of each
      interface were estimated, and dissociation rates were observed to be strongly
      dependent on temperature, with higher dissociation rates at larger over
      temperatures vis-a-vis melting. A simple coupled mass and heat transfer model
      developed previously was applied to fit the observed dissociation profiles, and
      this helps to identify clearly two distinct regimes of break-up; a second well
      defined region is essentially independent of composition and temperature, in
      which the remaining nanoscale, de facto two-dimensional system's lattice
      framework is intrinsically unstable. From equilibrium MD of the two-phase systems
      at their melting point, the relaxation times of the auto-correlation functions of
      fluctuations in number of enclathrated guest molecules were used as a basis for
      comparison of the variation in the underlying, non-equilibrium, thermal-driven
      dissociation rates via Onsager's hypothesis, and statistically significant
      differences were found, confirming the value of a fluctuation-dissipation
      approach in this case. 

PMID- 24028125
TI  - Stretch or contraction induced inversion of rectification in diblock molecular
      junctions.
AB  - Based on ab initio theory and nonequilibrium Green's function method, the effect
      of stretch or contraction on the rectification in diblock co-oligomer molecular
      diodes is investigated theoretically. Interestingly, an inversion of rectifying
      direction induced by stretching or contracting the molecular junctions, which is
      closely related to the number of the pyrimidinyl-phenyl units, is proposed. The
      analysis of the molecular projected self-consistent Hamiltonian and the evolution
      of the frontier molecular orbitals as well as transmission coefficients under
      external biases gives an inside view of the observed results. It reveals that the
      asymmetric molecular level shift and asymmetric evolution of orbital wave
      functions under biases are competitive mechanisms for rectification. The
      stretching or contracting induced inversion of the rectification is due to the
      conversion of the dominant mechanism. This work suggests a feasible technique to
      manipulate the rectification performance in molecular diodes by use of the
      mechanically controllable method. 

PMID- 24028126
TI  - Endohedral and exohedral complexes of substituted benzenes with carbon nanotubes
      and graphene.
AB  - Non-covalent complexes of cyclohexane and a series of substituted benzenes with
      short carbon nanotube (CNT) models are investigated primarily at the B97
      D3/TZV(2d,2p) level of theory. Understanding non-covalent interactions of arenes
      with CNTs is vital for the development of next-generation organic electronic
      materials and for harnessing CNTs as nano-reactors and vehicles for drug
      delivery. The interaction of benzene and cyclohexane with the interior and
      exterior of CNTs depends on the nanotube diameter, particularly for endohedral
      complexes. Both benzene and cyclohexane interact more strongly with the interior
      of CNTs than the outside, with benzene exhibiting stronger interactions than
      cyclohexane for CNTs larger than (8,8). Studies of two benzenes inside of CNTs
      predict the formation of one-dimensional sandwich and parallel-displaced stacks
      of benzenes within certain sized CNTs, which could have interesting
      optoelectronic properties. Concerning the impact of substituents on the
      interaction of benzene with CNTs, we find that electrostatic interactions do not
      control substituent effects. That is, the electron-donating or -withdrawing
      character of the substituents is not correlated with the predicted interaction
      energies. Moreover, substituent effects are the same for both endohedral and
      exohedral complexes, despite the different electronic character of the interior
      and exterior CNT walls. Ultimately, substituent effects in pi-stacking
      interactions with CNTs and graphene are explained by differences in dispersion
      interactions between the substituents and CNT walls or graphene surface. 

PMID- 24028127
TI  - Electro-osmotic flow of semidilute polyelectrolyte solutions.
AB  - We investigate electro-osmosis in aqueous solutions of polyelectrolytes using
      mean-field equations. A solution of positively charged polyelectrolytes is
      confined between two negatively charged planar surfaces, and an electric field is
      applied parallel to the surfaces. When electrostatic attraction between the
      polymer and the surface is strong, the polymers adhere to the surface, forming a
      highly viscous adsorption layer that greatly suppresses the electro-osmosis.
      Conversely, electro-osmosis is enhanced by depleting the polymers from the
      surfaces. We also found that the electro-osmotic flow is invertible when the
      electrostatic potential decays to its bulk value with the opposite sign. These
      behaviors are well explained by a simple mathematical form of the electro-osmotic
      coefficient. 

PMID- 24028128
TI  - Thermal fluctuations and bending rigidity of bilayer membranes.
AB  - We present a new scheme to estimate the elastic properties of biological
      membranes in computer simulations. The method analyzes the thermal fluctuations
      in terms of a coupled undulatory mode, which disentangle the mixing of the
      mesoscopic undulations and the high-q protrusions. This approach makes possible
      the accurate estimation of the bending modulus both for membranes under stress
      and in tensionless conditions; it also extends the applicability of the
      fluctuation analysis to the small membrane areas normally used in atomistic
      simulations. Also we clarify the difference between the surface tension imposed
      in simulations through a pressure coupling barostat, and the surface tension that
      can be extracted from the analysis of the low wave vector dependence of the
      coupled undulatory fluctuation spectrum. The physical analysis of the peristaltic
      mode is also refined, by separating the bulk and protrusions contributions. We
      illustrate the procedure by analyzing 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayers. The
      bending moduli obtained from our analysis, shows good agreement with available
      experiments. 

PMID- 24028129
TI  - Temperature-sensitive colloidal phase behavior induced by critical Casimir
      forces.
AB  - We report Monte Carlo simulations of phase behavior of colloidal suspensions with
      near-critical binary solvents using effective pair potentials from experiments.
      At off-critical solvent composition, the calculated phase diagram agrees well
      with measurements of the experimental system, indicating that many-body effects
      are limited. Close to the critical composition, however, agreement between
      experiment and simulation becomes poorer, signaling the increased importance of
      many-body effects. Both at and off the critical solvent concentration, the
      colloidal phase diagram is qualitatively similar to those of molecular systems
      and obeys the principle of corresponding states with one striking difference: it
      occurs in a narrow temperature interval of <1  degrees C below the solvent phase
      separation temperature. 

PMID- 24028130
TI  - Modeling lower critical solution temperature behavior of associating polymer
      brushes with classical density functional theory.
AB  - We study the lower critical solution temperature (LCST) behavior of associating
      polymer brushes (i.e., poly(N-isopropylacrylamide)) using classical density
      functional theory. Without using any empirical or temperature-dependent
      parameters, we find the phase transition of polymer brushes from extended to
      collapsed structure with increasing temperature, indicating the LCST behavior of
      polymer brushes. The LCST behavior of associating polymer brushes is attributed
      to the interplay of hydrogen bonding interactions and Lennard-Jones attractions
      in the system. The effect of grafting density and molecular weight on the phase
      behavior of associating polymer brushes has been also investigated. We find no
      LCST behavior at low grafting density or molecular weight. Moreover, increasing
      grafting density decreases the LCST and swelling ratio of polymer brushes.
      Similarly, increasing molecular weight decreases the LCST but increases the
      swelling ratio. At very high grafting density, a partial collapsed structure
      appears near the LCST. Qualitatively consistent with experiments, our results
      provide insight into the molecular mechanism of LCST behavior of associating
      polymer brushes. 

PMID- 24028131
TI  - DNA overstretching transition induced by melting in a dynamical mesoscopic model.
AB  - We present a phenomenological dynamical model describing the force induced
      melting as responsible for the DNA overstretching transition. The denaturation
      mechanism is developed under the framework of the mesoscopic one-dimensional
      Peyrard-Bishop-Dauxois (PBD) picture which models the melting features of a
      polymer chain by means of a Morse potential and the stacking interaction. We find
      a good agreement with both the experimental overstretching curve and the
      asymmetric hysteretic properties with different simulation times. The comparison
      of the standard PBD model with a modification of the Morse potential which takes
      into account the interaction with the solvent has been also successfully
      investigated. 

PMID- 24028132
TI  - A coarse grain model for protein-surface interactions.
AB  - The interaction of proteins with surfaces is important in numerous applications
      in many fields-such as biotechnology, proteomics, sensors, and medicine--but
      fundamental understanding of how protein stability and structure are affected by
      surfaces remains incomplete. Over the last several years, molecular simulation
      using coarse grain models has yielded significant insights, but the formalisms
      used to represent the surface interactions have been rudimentary. We present a
      new model for protein surface interactions that incorporates the chemical
      specificity of both the surface and the residues comprising the protein in the
      context of a one-bead-per-residue, coarse grain approach that maintains
      computational efficiency. The model is parameterized against experimental
      adsorption energies for multiple model peptides on different types of surfaces.
      The validity of the model is established by its ability to quantitatively and
      qualitatively predict the free energy of adsorption and structural changes for
      multiple biologically-relevant proteins on different surfaces. The validation,
      done with proteins not used in parameterization, shows that the model produces
      remarkable agreement between simulation and experiment.

PMID- 24028133
TI  - Note: Effects of polydispersity on the phase behavior of AB diblock and BAB
      triblock copolymer melts: A dissipative particle dynamics simulation study.

PMID- 24028134
TI  - Note: Homogeneous TIP4P/2005 ice nucleation at low supercooling.
AB  - We present a partial free energy profile for the homogeneous nucleation of ice
      using an all-atom model of water at low supercooling, at which ice growth
      dynamics are reasonably accessible to simulation. We demonstrate that the free
      energy profile is well described by classical nucleation theory, and that the
      nucleation barrier is entropic in origin. We also estimate to first order the
      temperature dependence of the interfacial free energy. 

PMID- 24028135
TI  - Note: Manipulation of supersonic atomic beams with static magnetic fields.
AB  - The inhomogeneous magnetic field of a permanent-magnet planar Halbach array is
      used to either deflect or to specularly reflect a supersonic beam of neutral
      atoms. Metastable neon and helium beams are tested to experimentally evaluate the
      performance of this array in a range of configurations. Results are compared with
      numerical simulations and the device is presented as a high precision tool for
      the manipulation of neutral atom beams. 

PMID- 24028137
TI  - Social media as a research environment.

PMID- 24028138
TI  - Can Facebook use induce well-being?
AB  - Over the past few decades, the widespread phenomenon of Internet abuse has gained
      attention from the public, academia, and the media. In a departure from this
      negative viewpoint, however, researchers and educators have devoted considerable
      effort in attempting to understand the influence of online communication on
      people's psychological well-being. This study focuses specifically on Facebook,
      and proposes a research model to examine the relationships among Facebook use,
      online social support, general social support, and psychological well-being. Our
      results show that using Facebook helped college students to obtain online social
      support, and that online social support is an extension of general social
      support. However, although general social support contributes to well-being,
      online social support appears to have little direct effect on well-being. The
      relationship between online social support and well-being is mediated through the
      factor of general social support.

PMID- 24028141
TI  - Genes for iron-sulphur cluster assembly are targets of abiotic stress in rice,
      Oryza sativa.
AB  - Iron-sulphur (Fe-S) cluster assembly occurs in chloroplasts, mitochondria and
      cytosol, involving dozens of genes in higher plants. In this study, we have
      identified 41 putative Fe-S cluster assembly genes in rice (Oryza sativa) genome,
      and the expression of all genes was verified. To investigate the role of Fe-S
      cluster assembly as a metabolic pathway, we applied abiotic stresses to rice
      seedlings and analysed Fe-S cluster assembly gene expression by qRT-PCR. Our data
      showed that genes for Fe-S cluster assembly in chloroplasts of leaves are
      particularly sensitive to heavy metal treatments, and that Fe-S cluster assembly
      genes in roots were up-regulated in response to iron toxicity, oxidative stress
      and some heavy metal assault. The effect of each stress treatment on the Fe-S
      cluster assembly machinery demonstrated an unexpected tissue or organelle
      specificity, suggesting that the physiological relevance of the Fe-S cluster
      assembly is more complex than thought. Furthermore, our results may reveal
      potential candidate genes for molecular breeding of rice. 

PMID- 24028143
TI  - Geographical and social influences on genetic diversity within the Egyptian
      population: analyses of Alu insertion polymorphisms.
AB  - BACKGROUND: The geographical location of Egypt at the crossroads of several major
      cultural areas between North Africa and the Middle East has contributed to its
      population history. AIM: To analyse the genetic structure of the population
      living in two geographical parts of Egypt. SUBJECTS AND METHODS: A sample of 112
      Egyptians from the North African part of Egypt (Ismailia sample) and a sample of
      52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion
      polymorphisms. RESULTS: The results of the present study showed a significant
      genetic difference between the Sinai and Ismailia samples. The latter showed an
      evident genetic affinity with North African populations; whereas the Sinai sample
      was found to be genetically closer to the Middle East populations. The Sinai
      sample showed a low average heterozygosity, unlike that found in the Ismailia
      sample. CONCLUSION: This study provides new insights into the genetic structure
      of the Egyptian population living in a land bridge between Africa and Asia.
      Results suggest a genetic discontinuity between the Sinai population and that of
      the North African part of Egypt. This discontinuity would have been maintained
      thanks to geo-climatic and social factors.

PMID- 24028142
TI  - Differential contribution of isoaspartate post-translational modifications to the
      fibrillization and toxic properties of amyloid beta and the Asn23 Iowa mutation.
AB  - Mutations within the Abeta (amyloid beta) peptide, especially those clustered at
      residues 21-23, are linked to early-onset AD (Alzheimer's disease) and primarily
      associated with cerebral amyloid angiopathy. The Iowa variant, a substitution of
      an aspartic acid residue for asparagine at position 23 (D23N), associates with
      widespread vascular amyloid and abundant diffuse pre-amyloid lesions
      significantly exceeding the incidence of mature plaques. Brain Iowa deposits
      consist primarily of a mixture of mutated and non-mutated Abeta species
      exhibiting partial aspartate isomerization at positions 1, 7 and 23. The present
      study analysed the contribution of the post-translational modification and the
      D23N mutation to the aggregation/fibrillization and cell toxicity properties of
      Abeta providing insight into the elicited cell death mechanisms. The induction of
      apoptosis by the different Abeta species correlated with their
      oligomerization/fibrillization propensity and beta-sheet content. Although cell
      toxicity was primarily driven by the D23N mutation, all Abeta isoforms tested
      were capable, albeit at different time frames, of eliciting comparable apoptotic
      pathways with mitochondrial engagement and cytochrome c release to the cytoplasm
      in both neuronal and microvascular endothelial cells. Methazolamide, a cytochrome
      c release inhibitor, exerted a protective effect in both cell types, suggesting
      that pharmacological targeting of mitochondria may constitute a viable
      therapeutic avenue.

PMID- 24028144
TI  - Changes of adiponectin and its receptors in rats following chronic renal failure.
AB  - OBJECTIVE: To investigate changes of adiponectin and its receptors (Adipo R) in
      rats following chronic renal failure. METHODS: Male SD rats were randomly divided
      into two groups: control group and chronic renal failure (CRF) group. The CRF
      group were gavaged with adenine (300 mg/kg/d) for 4 weeks and the control group
      with drinking water. All rats were anesthetized at 2nd or 4th week and blood and
      urine samples were collected for detection of renal function, 24 h urine protein
      and adiponectin concentration. Renal tissues were also collected for HE staining,
      immunohistochemistry and RT-PCR screening. RESULTS: Compared with control group,
      the serum concentrations of urea and creatinine, 24 h urine protein excretion in
      the CRF group were significantly higher at 2nd week and further increased at 4th
      week (p < 0.05). The adiponectin levels in serum and urine in the CRF group were
      significantly higher than those of control group (p < 0.01). The renal
      expressions of Adipo R1 and Adipo R2 in CRF group were also significantly
      increased compared to control group (p < 0.01). The increased expressions of
      Adipo R1 and Adipo R2 were positively related to the adiponectin levels in serum,
      urine, and 24 h urine protein. CONCLUSION: The significant changes in expression
      of adiponectin and its receptors in rat CRF model could be an adaptive response
      that may provide the basis to understand pathological changes in chronic kidney
      disease.

PMID- 24028146
TI  - Cytoreductive surgery and post-operative heated pleural chemotherapy for the
      management of pleural surface malignancy.
AB  - PURPOSE: We retrospectively analysed the long-term outcomes of cytoreductive
      surgery and post-operative heated pleural chemotherapy (HPC) for thoracic
      malignancies with pleural spread. MATERIALS AND METHODS: Between 1987 and 2010,
      160 patients were enrolled. There were 101 patients with non-small cell lung
      cancer (NSCLC), 25 with malignant pleural mesothelioma (MPM), 12 with thymoma,
      and 22 with tumours metastatic to the lung and pleura. Immediately after intra
      thoracic administration of cisplatin or carboplatin, hyperthermia was performed
      by using an 8.00 MHz radiofrequency capacitive heating device for 1 to 4 courses
      in each patient. RESULTS: There was no systemic toxicity or treatment-related
      mortality. Five-year overall survival rates were 37.4% in NSCLC, 15.9% in MPM,
      91.7% in thymoma, and 25.8% in metastatic lung tumour. Five-year local relapse
      free survival (RFS) rates were 55.2% in NSCLC, 24.4% in MPM, 64.8% in thymoma,
      and 27.2% in tumours metastatic to the lung and pleura. When 101 NSCLCs were
      categorised into pleural lavage cytology positive (grade 1: n = 37), limited
      extent of carcinomatous pleuritis (grade 2: n = 21), and extensive carcinomatous
      pleuritis (grade 3: n = 43), 5-year overall survival rates were 62.5%, 49.2%, and
      13.6%, respectively. The local RFS was significantly better in group 1/2 than in
      group 3. CONCLUSIONS: Although our study has some of the usual weaknesses of a
      single institution retrospective study, cytoreductive surgery and HPC are
      feasible and safe. It is suggested that HPC may have a potential role for local
      control as adjuvant treatment for cytoreductive surgery in patients with minor
      pleural spread.

PMID- 24028147
TI  - Are radiology visual skills one dimension in undergraduate medical education?

PMID- 24028148
TI  - Nuclear magnetic resonance at the picomole level of a DNA adduct.
AB  - We investigate the limit of detection for obtaining NMR data of a DNA adduct
      using modern microscale NMR instrumentation, once the adduct has been isolated at
      the picomole level. Eighty nanograms (130 pmol) of a DNA adduct standard, N-(2'
      deoxyguanosin-8-yl)-2-acetylaminofluorene 5'-monophosphate (AAF-dGMP), in 1.5 MUL
      of D2O with 10% methanol-d4, in a vial, was completely picked up as a droplet
      suspended in a fluorocarbon liquid and loaded efficiently into a microcoil probe.
      This work demonstrates a practical manual method of droplet microfluidic sample
      loading, previously demonstrated using automated equipment, which provides a
      severalfold advantage over conventional flow injection. Eliminating dilution
      during injection and confining the sample to the observed volume produce the full
      theoretical mass sensitivity of a microcoil, comparable to that of a microcryo
      probe. With 80 ng, an NMR spectrum acquired over 40 h showed all of the
      resonances seen in a standard spectrum of AAF-dGMP, with a signal-to-noise ratio
      of at least 10, despite broadening due to previously noted effects of
      conformational exchange. Even with this broadening to 5 Hz, a two-dimensional
      total correlation spectroscopy spectrum was acquired on 1.6 MUg in 18 h. This
      work helps to define the utility of NMR in combination with other analytical
      methods for the structural characterization of a small amount of a DNA adduct.

PMID- 24028149
TI  - Identification of a new class of small molecules that efficiently reactivate
      latent Epstein-Barr Virus.
AB  - Epstein-Barr Virus (EBV) persists as a latent infection in many lymphoid and
      epithelial malignancies, including Burkitt's lymphomas, nasopharyngeal
      carcinomas, and gastric carcinomas. Current chemotherapeutic treatments of EBV
      positive cancers include broad-spectrum cytotoxic drugs that ignore the EBV
      positive status of tumors. An alternative strategy, referred to as oncolytic
      therapy, utilizes drugs that stimulate reactivation of latent EBV to enhance the
      selective killing of EBV-positive tumors, especially in combination with existing
      inhibitors of herpesvirus lytic replication, like Ganciclovir (GCV). At present,
      no small molecule, including histone deacetylase (HDAC) inhibitors, have proven
      safe or effective in clinical trials for treatment of EBV-positive cancers.
      Aiming to identify new chemical entities that induce EBV lytic cycle, we have
      developed a robust high-throughput cell-based assay to screen 66,840 small
      molecule compounds. Five structurally related tetrahydrocarboline derivatives
      were identified, two of which had EC50 measurements in the range of 150-170 nM.
      We show that these compounds reactivate EBV lytic markers ZTA and EA-D in all EBV
      positive cell lines we have tested independent of the type of latency. The
      compounds reactivate a higher percentage of latently infected cells than HDAC
      inhibitors or phorbol esters in many cell types. The most active compounds showed
      low toxicity to EBV-negative cells but were highly effective at selective cell
      killing of EBV-positive cells when combined with GCV. We conclude that we have
      identified a class of small molecule compounds that are highly effective at
      reactivating latent EBV infection in a variety of cell types and show promise for
      lytic therapy in combination with GCV. 

PMID- 24028150
TI  - Emodin inhibits ATP-induced IL-1beta secretion, ROS production and phagocytosis
      attenuation in rat peritoneal macrophages via antagonizing P2X7 receptor.
AB  - CONTEXT: Previous in vitro studies have demonstrated that emodin (1,3,8
      trihydroxy-6-methyl-anthraquinone), an anthraquinone derivative from the rhizome
      of Rheum palmatum L., can inhibit the activation of P2X7 receptors (P2X7R) as a
      potential antagonist. However, the effects of emodin on P2X7R-related
      inflammatory processes remain unclear. OBJECTIVE: This study aimed to investigate
      the effects of emodin on different inflammation responses of macrophages induced
      by ATP, the natural ligand of P2X7R. MATERIALS AND METHODS: Rat peritoneal
      macrophages were treated with millimolar ATP and emodin (0.1, 0.3, 1, 3, 10 uM)
      or brilliant blue G (BBG, 0.1, 1, 10 uM). Cytosolic Ca2+ concentration ([Ca2+]c)
      was detected by fluorescent Ca2+ imaging. Interleukin-1beta (IL-1beta) release
      was measured by rat IL-1beta ELISA kits. Reactive oxygen species (ROS) generation
      was examined by dihydroethidium (DHE) fluorescent staining. Phagocytic activity
      was tested by neutral red uptake assay. RESULTS: We found that the [Ca2+](c)
      increase evoked by ATP (5 mM) was inhibited by emodin, in a dose-dependent manner
      with IC50 of 0.5 MUM. Furthermore, emodin reduced the IL-1beta release induced by
      ATP (2 mM) in lipopolysaccharide (LPS)-activated macrophages, with an IC50 of 1.6
      MUM. Emodin also strongly suppressed the ROS production and phagocytosis
      attenuation triggered by ATP (1 mM), with IC50 values of 1 MUM and 0.7 MUM,
      respectively. Besides, BBG, a specific antagonist of P2X7R, exhibited similar
      suppressive effects on these inflammation responses. CONCLUSION: These results
      showed the inhibitory effects of emodin on ATP-induced [Ca2+](c) increase, IL
      1beta release, ROS production and phagocytosis attenuation in rat peritoneal
      macrophages, by inhibiting the activation of P2X7R.

PMID- 24028151
TI  - Comparison of characteristics between nonobese and overweight/obese subjects with
      nonalcoholic fatty liver disease in a South Indian population.
AB  - AIMS: This study was designed to compare the characteristics of nonobese and
      overweight/obese subjects with nonalcoholic fatty liver disease (NAFLD) in an
      urban South Indian population. SUBJECTS AND METHODS: The study group comprises
      541 subjects drawn from the Chennai Urban Rural Epidemiology Study (CURES), which
      was carried out on a representative sample of Chennai city in southern India.
      NAFLD was diagnosed by ultrasonography. Subjects with NAFLD were classified as
      nonobese (body mass index of <=22.9 kg/m(2)) and overweight/obese (body mass
      index of >=23 kg/m(2)) based on World Health Organization Asia Pacific
      guidelines. Coronary artery disease (CAD) was assessed by a resting 12-lead
      electrocardiogram that was Minnesota-coded. Insulin resistance was assessed by
      using the homeostasis assessment model (HOMA-IR) using the following formula:
      fasting insulin (MUIU/mL)*fasting glucose (mmol/L)/22.5. RESULTS: In total, 173
      of 541 (32%) subjects had NAFLD, of whom 48 (27.7%) had nonobese NAFLD and 125
      (72.3%) had overweight/obese NAFLD. Compared with overweight/obese NAFLD
      patients, fasting blood glucose (104+/-29 vs. 119+/-45 mg/dL; P<0.05) and HOMA-IR
      (2.1+/-1.8 vs. 2.9+/-1.8; P<0.001) were lower and high-density lipoprotein
      cholesterol (43+/-9 vs. 39+/-8 mg/dL; P<0.001) was higher among nonobese NAFLD
      subjects. Multiple logistic regression analysis showed a significant association
      between nonobese NAFLD and CAD (P=0.013) even after adjusting for age, diabetes,
      hypercholesterolemia, HOMA-IR, and hypertension. CONCLUSIONS: This study suggests
      that even nonobese NAFLD subjects have an association with CAD.

PMID- 24028152
TI  - Assessment of cells in the ascitic fluid of women with ovarian hyperstimulation
      syndrome: the clinical implications for subsequent ovarian malignancy.
AB  - BACKGROUND: Although some studies have reported a potential connection between
      ovulation induction therapy (OIT) and malignant ovarian diseases, the results
      have been inconclusive. In the present study, we sought to determine whether
      women undergoing OIT at our in vitro fertilization (IVF) clinic, especially those
      with severe ovarian hyperstimulation syndrome (OHSS) and suspicious cytologic
      findings, were at risk for developing malignant ovarian tumours after treatment.
      METHODS: Patients who underwent OIT at our IVF clinic were enrolled in this study
      and assessed for any evidence of malignant ovarian tumours. Patients who
      developed severe OHSS as a result of OIT were treated with a culdocentesis. Cells
      from the ascitic fluid were cytologically scored for abnormality and malignancy.
      Peripheral blood samples were obtained from patients with severe OHSS to
      determine serum levels of the tumour markers (CA-125 and HE4) that were used to
      calculate the Risk for Ovarian Malignancy Algorithm (ROMA) index. RESULTS: Follow
      up data were available for 1,353 of the 1,587 patients (85%) who underwent OIT at
      our IVF clinic between January 2006 and December 2012. Twenty-three patients
      (1.4%) were hospitalized with OHSS. Culdocentesis was performed 16 times in nine
      patients with severe OHSS (age range, 23-34 years; mean, 27.1 years). Although
      cytological examination of the ascitic cells of these patients suggested
      malignant ovarian neoplasia, over the course of the observation period, the
      ovarian volume gradually decreased and became normal. Subsequent cytological and
      histological examinations failed to find evidence of any malignant tumours in
      these nine patients. None of the 1,353 participants who underwent OIT developed
      any malignant ovarian tumours during the study period. Moreover, none of the 462
      patients who were in our ovarian tumour registry were also participants in the
      IVF program. CONCLUSIONS: The presence of atypical cells in the ascitic fluid of
      women with severe OHSS does not likely indicate malignancy; therefore, radical
      surgical intervention is not justified. The risk of malignancy is minimal shortly
      after OIT. At our centre, OIT has not been associated with any cases of ovarian
      tumour.

PMID- 24028155
TI  - Inside versus outside: ion redistribution in nitric acid reacted sea spray
      aerosol particles as determined by single particle analysis.
AB  - Single particle analysis of individual sea spray aerosol particles shows that
      cations (Na(+), K(+), Mg(2+), and Ca(2+)) within individual particles undergo a
      spatial redistribution after heterogeneous reaction with nitric acid, along with
      the development of a more concentrated layer of organic matter at the surface of
      the particle. These data suggest that specific ion and aerosol pH effects play an
      important role in aerosol particle structure in ways that have not been
      previously recognized. 

PMID- 24028154
TI  - Identification and functional characterization of a rice NAC gene involved in the
      regulation of leaf senescence.
AB  - BACKGROUND: As the final stage of leaf development, leaf senescence may cause the
      decline of photosynthesis and gradual reduction of carbon assimilation, which
      makes it a possible limiting factor for crop yield. NACs are plant-specific
      transcription factors and some NACs have been confirmed to play important roles
      in regulating leaf senescence. RESULTS: In this study, we reported a member of
      the NAC transcription factor family named OsNAP whose expression is associated
      with leaf senescence, and investigated its preliminary function during the
      process of leaf senescence. The results of qRT-PCR showed that the OsNAP
      transcripts were accumulated gradually in response to leaf senescence and
      treatment with methyl jasmonic acid (MeJA). A subcellular localization assay
      indicated that OsNAP is a nuclear-localized protein. Yeast one-hybrid experiments
      indicated that OsNAP can bind the NAC recognition site (NACRS)-like sequence.
      OsNAP-overexpressing transgenic plants displayed an accelerated leaf senescence
      phenotype at the grain-filling stage, which might be caused by the elevated JA
      levels and the increased expression of the JA biosynthesis-related genes LOX2 and
      AOC1, and showed enhanced tolerance ability to MeJA treatment at the seedling
      stage. Nevertheless, the leaf senescence process was delayed in OsNAP RNAi
      transgenic plants with a dramatic drop in JA levels and with decreased expression
      levels of the JA biosynthesis-related genes AOS2, AOC1 and OPR7. CONCLUSIONS:
      These results suggest that OsNAP acts as a positive regulator of leaf senescence
      and this regulation may occur via the JA pathway.

PMID- 24028156
TI  - FeCl3.6H2O, a catalyst for the diastereoselective synthesis of cis-isoxazolidines
      from N-protected delta-hydroxylamino allylic acetates.
AB  - An ecofriendly and diastereoselective synthesis of cis-3,5-disubstituted
      isoxazolidines through the FeCl3.6H2O-catalyzed cyclization of delta
      hydroxylamino allylic acetates is described. The synthetic potential of these
      products is highlighted by the preparation of several functionalized 1,3-amino
      alcohol precursors. 

PMID- 24028157
TI  - Acute adrenal insufficiency following arthroplasty: a case report and review of
      the literature.
AB  - BACKGROUND: Acute adrenal insufficiency is a potentially lethal condition rarely
      caused by bilateral adrenal haemorrhage due to heparin use. Most of the times, it
      is difficult to establish the diagnosis, as symptoms are not specific. Few cases
      have been reported in the literature. CASE PRESENTATION: A 52-year-old Caucasian
      woman presented with abdominal pain, vomiting and weakness nine days after
      arthroplasty and heparin use. Hyperkalemia, low cortisol and high
      adrenocorticotropic hormone levels were found, indicating adrenal insufficiency.
      Magnetic resonance imaging of the upper abdomen was compatible with preceding
      adrenal haemorrhage. Hydrocortisone and fludrocortisone were administered. Review
      of the literature revealed 36 cases of postoperative adrenal haemorrhage which
      are presented briefly. CONCLUSION: Postoperative acute adrenal insufficiency due
      to haemorrhage is a rare condition. If patients are treated based on clinical
      suspicion, they have good chances to survive. Hydrocortisone is given permanently
      in the majority of the patients.

PMID- 24028159
TI  - Emerging aspects of food and nutrition on gut microbiota.
AB  - The human gastrointestinal tract contains a highly complex ecosystem that harbors
      various microorganisms, which together create a unique environment within each
      individual. There is growing awareness that dietary habits are one of the
      essential factors contributing to the microbial diversity and community
      configuration that ultimately affects human health. From an evolutionary
      perspective, human dietary history can be viewed as a central factor in the
      selection of the gut microbial community and stabilization of the mutualistic
      host-microbial interaction, that together drive host phenotype. Herein, current
      knowledge concerning the influence of major dietary macrostructure and individual
      food ingredients is presented. This knowledge will provide perspectives for
      personalized gut microbiota management and, ultimately, movement toward an era of
      personalized nutrition and medicine. 

PMID- 24028158
TI  - Validity of a computer-assisted manual segmentation software to quantify wrist
      erosion volume using computed tomography scans in rheumatoid arthritis.
AB  - BACKGROUND: To investigate the performance of conventional radiography (CR) for
      the detection of bone erosions of wrist in rheumatoid arthritis (RA) using
      multidetector computed tomography (CT) as the reference method and to evaluate
      the validity of a computer-assisted manual segmentation (outlining) technique to
      quantify erosion volume on CT scans. METHODS: Twenty five RA patients and six
      controls underwent CT and radiographic evaluation of the dominant wrist on the
      same day. CT was performed by using a 64 GE light Speed VCT power. Wrists images
      were evaluated separately and scored for the presence of erosions according to
      the Outcome Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System
      (RAMRIS) and the Sharp/van der Heijde scoring method. Measurements of bone
      erosion volumes were obtained using OsiriX medical imaging software. The mean
      value of the volumes of the CT bone erosions detected at two readings was used to
      calculate inter-rater agreement. RESULTS: The overall sensitivity, specificity
      and accuracy of radiography for detecting erosions were 25.5%, 98.3% and 70.1%,
      respectively. Using computer-assisted manual segmentation (outlining) technique,
      erosion volume on CT measurements per subject was ranged from 0.001 cm3 to 2.01
      cm3. Spearman's RAMRIS score of each wrist bones in all subjects (n = 25) were
      correlated with the total erosion volume on CT (p < 0.0001), with the ratio
      between erosion volume and the corresponding bone volume on a percentage basis (p
      < 0.0001). The total Sharp/van der Heijde erosion score of the all wrist bones
      was correlate with the RAMRIS score (p = 0.008). The intraclass correlation
      coefficients (ICC) for manual segmentation showed high agreement (ICC = 0.901).
      CONCLUSIONS: Considering CT as the reference method, CR showed very low
      sensitivity. A close correlation with CT erosion volumes supports the OMERACT
      RAMRIS erosion score as a semiquantitative measure of joint damage in RA.
      Although the computer-assisted manual segmentation can be beneficial for
      diagnostic decision in cross-sectional CT examinations of the wrist in RA, this
      technique will require further evaluation in terms of responsiveness.

PMID- 24028160
TI  - Relation between exhaled nitric oxide and left ventricular performance in chronic
      hemodialysis patients.
AB  - INTRODUCTION: End-stage renal disease is the most debilitating condition for
      patients with renal diseases. Cardiovascular disease is the leading cause of
      death in these patients. It has been shown that nitric oxide (NO) increases in
      renal failure and hemodialysis patients and could be correlated with
      cardiovascular diseases in this population. OBJECTIVES: To investigate the
      relation between exhaled nitric oxide (eNO) and left ventricular performance in
      chronic hemodialysis patients. METHODS: In this prospective study, eNO was
      measured in 20 chronic hemodialysis patients (13 males and 7 females with the
      mean age of 45.20 +/- 14.99 years). Left ventricular findings were studied by
      conventional and Doppler echocardiography. eNO correlation with the
      echocardiographic parameters was evaluated. RESULTS: The median eNO was 11.65 ppb
      (range: 1.9-29.9 ppb). eNO was positively correlated with left ventricular
      ejection fraction (rho = 0.561, p = 0.01) and negatively correlated with left
      ventricular end systolic volume (rho = -0.451, p = 0.046), isovolumic relaxation
      time (rho = -0.448, p = 0.047) and myocardial performance index (rho = -0.587, p
      = 0.007). CONCLUSION: There is a positive correlation between eNO and left
      ventricular performance in chronic hemodialysis patients. Therefore, eNO may play
      an important role in pathophysiology of cardiac involvement in these patients.

PMID- 24028161
TI  - Structures and target recognition modes of PDZ domains: recurring themes and
      emerging pictures.
AB  - PDZ domains are highly abundant protein-protein interaction modules and are often
      found in multidomain scaffold proteins. PDZ-domain-containing scaffold proteins
      regulate multiple biological processes, including trafficking and clustering
      receptors and ion channels at defined membrane regions, organizing and targeting
      signalling complexes at specific cellular compartments, interfacing cytoskeletal
      structures with membranes, and maintaining various cellular structures. PDZ
      domains, each with ~90-amino-acid residues folding into a highly similar
      structure, are best known to bind to short C-terminal tail peptides of their
      target proteins. A series of recent studies have revealed that, in addition to
      the canonical target-binding mode, many PDZ-target interactions involve amino
      acid residues beyond the regular PDZ domain fold, which we refer to as
      extensions. Such extension sequences often form an integral structural and
      functional unit with the attached PDZ domain, which is defined as a PDZ
      supramodule. Correspondingly, PDZ-domain-binding sequences from target proteins
      are frequently found to require extension sequences beyond canonical short C
      terminal tail peptides. Formation of PDZ supramodules not only affords necessary
      binding specificities and affinities demanded by physiological functions of PDZ
      domain targets, but also provides regulatory switches to be built in the PDZ
      target interactions. At the 20th anniversary of the discovery of PDZ domain
      proteins, we try to summarize structural features and target-binding properties
      of such PDZ supramodules emerging from studies in recent years. 

PMID- 24028165
TI  - Two cases of reversible left ventricular hypertrophy during recovery from
      takotsubo cardiomyopathy: hypertrophy or myocardial edema after an attack of
      takotsubo syndrome?

PMID- 24028166
TI  - Reply: To PMID 23406010.

PMID- 24028167
TI  - Acute mitral regurgitation in suspected acute coronary syndrome: what is the
      cause?: Transient mitral regurgitation and/or left ventricular wall-motion
      abnormalities: common formes frustes of takotsubo syndrome?

PMID- 24028168
TI  - Reply: To PMID 23489024.

PMID- 24028171
TI  - Review: comparison of PET rubidium-82 with conventional SPECT myocardial
      perfusion imaging.
AB  - Nuclear cardiology has for many years been focused on gamma camera technology.
      With ever improving cameras and software applications, this modality has
      developed into an important assessment tool for ischaemic heart disease. However,
      the development of new perfusion tracers has been scarce. While cardiac positron
      emission tomography (PET) so far largely has been limited to centres with on-site
      cyclotron, recent developments with generator produced perfusion tracers such as
      rubidium-82, as well as an increasing number of PET scanners installed, may
      enable a larger patient flow that may supersede that of gamma camera myocardial
      perfusion imaging. 

PMID- 24028172
TI  - The combined effect of salinity and heat reveals a specific physiological,
      biochemical and molecular response in tomato plants.
AB  - Many studies have described the response mechanisms of plants to salinity and
      heat applied individually; however, under field conditions some abiotic stresses
      often occur simultaneously. Recent studies revealed that the response of plants
      to a combination of two different stresses is specific and cannot be deduced from
      the stresses applied individually. Here, we report on the response of tomato
      plants to a combination of heat and salt stress. Interestingly, and in contrast
      to the expected negative effect of the stress combination on plant growth, our
      results show that the combination of heat and salinity provides a significant
      level of protection to tomato plants from the effects of salinity. We observed a
      specific response of plants to the stress combination that included accumulation
      of glycine betaine and trehalose. The accumulation of these compounds under the
      stress combination was linked to the maintenance of a high K(+) concentration and
      thus a lower Na(+) /K(+) ratio, with a better performance of the cell water
      status and photosynthesis as compared with salinity alone. Our findings unravel
      new and unexpected aspects of the response of plants to stress combination and
      provide a proposed list of enzymatic targets for improving crop tolerance to the
      abiotic field environment. 

PMID- 24028173
TI  - Promoting positive attitudes to breastfeeding: the development and evaluation of
      a theory-based intervention with school children involving a cluster randomised
      controlled trial.
AB  - The objective of this study was to design, implement and evaluate an intervention
      based on the theory of planned behaviour (TPB) to enhance young peoples'
      motivations to breastfeed/support a partner to breastfeed. Six semi-structured
      focus groups were first conducted with 48 13-14-year-olds from two schools in
      Northern Ireland. The salient beliefs elicited were subsequently used to design a
      TPB-based questionnaire that was then administered to 2021 13-14-year-old pupils
      (852 males; 1169 females) from 36 post-primary schools to identify the most
      important determinants of breastfeeding. The results were used to inform the
      design and implementation of an intervention package that was subsequently
      evaluated using a cluster randomised controlled trial involving 44 randomly
      selected schools across Northern Ireland. Questionnaires were administered to 18
      intervention and 26 control schools at baseline and again at 1 and 6 months post
      intervention to evaluate its effectiveness. Multi-level modelling was employed to
      analyse the data. The results revealed significant effects on women's intention
      to breastfeed, beta = 0.208, t(1275) = 2.715, P = 0.007; attitudes, beta = 0.223,
      t(1275) = 4.655, P < 0.001; moral attitudes, beta = 0.231, t(1275) = 4.211, P <
      0.001; subjective norm, beta = 0.118, t(1275) = 2.521, P = 0.012; and knowledge,
      beta = 0.109, d.f. (1275) = 7.843, P < 0.001. However, for men, the results
      revealed significant effects on only the construct of knowledge, beta = 0.104,
      t(541) = 4.345, P < 0.001.The research has provided evidence to support the need
      for breastfeeding education in schools and has shown how a theoretical framework
      may be used to inform the design and evaluation of a health behaviour
      intervention. 

PMID- 24028174
TI  - The use of zebrafish as a model system for investigating the role of the SULTs in
      the metabolism of endogenous compounds and xenobiotics.
AB  - In recent years, zebrafish has emerged as a useful animal model for biomedical
      research. The deciphering of the zebrafish genome has revealed that many of the
      enzymes involved in the metabolism of endogenous compounds and xenobiotics are
      conserved between zebrafish and humans. This review summarizes the information
      currently available concerning the zebrafish cytosolic sulfotransferases (SULTs),
      a group of phase II enzymes that have been proposed to be involved in the
      regulation and homeostasis of key endogenous compounds and the detoxification of
      xenobiotics. To date, 20 zebrafish SULTs that fall into six major SULT gene
      families have been identified. Of the 20 SULTs 18 have been cloned, expressed,
      purified and characterized. These zebrafish SULTs were shown to exhibit
      differential substrate specificities for endogenous compounds such as monoamine
      transmitters, steroid/thyroid hormones and bile salts, as well as xenobiotics
      including environmental toxicants and drugs. These findings provide a foundation
      for using zebrafish as a model for investigating further the physiological,
      pharmacological, and toxicological involvement of the SULTs.

PMID- 24028175
TI  - Expression of the sulfotransferase 1C family: implications for xenobiotic
      toxicity.
AB  - The SULT1C enzymes are a relatively under-studied branch of the cytosolic
      sulfotransferase (SULT) multigene family. Concrete information about SULT1C
      tissue-specific expression, substrate preference, role in physiology and
      regulation is just emerging in the literature. The role of SULT1Cs in normal
      physiology is uncertain, but SULT1C-catalyzed sulfonation of thyroid hormones may
      be a mechanism to titrate the pre-receptor levels of biologically active thyroid
      hormone in target tissues. Both rat and human cytosolic SULT1Cs are most noted
      for their ability to bioactivate potent procarcinogens such as N-hydroxy-2
      acetylaminofluorene. This implicates a possible role for the SULT1Cs as
      modulators of environmental carcinogen exposure and determinants of neoplastic
      transformation. In humans, the SULT1Cs are likely to function physiologically in
      cell proliferation and organogenesis pathways during development, as SULT1Cs
      appear to be preferentially expressed during fetal life. In recent years, the
      SULT1C nomenclature as presented in the literature has undergone major changes in
      response to updated genomic information. The purpose of this review is to
      summarize the current literature on the SULT1Cs and to clarify perspectives on
      SULT1C species differences, tissue-specific expression, nomenclature and role in
      pathophysiology. The ultimate goal is to understand the undiscovered impact of
      SULT1C expression on hormone homeostasis and xenobiotic toxicity during human
      development and as a prelude to disease development later in life.

PMID- 24028176
TI  - Turkish translation and adaptation of Champion's Health Belief Model Scales for
      breast cancer mammography screening.
AB  - AIMS AND OBJECTIVES: To examine the translation and adaptation process from
      English to Turkish and the validity and reliability of the Champion's Health
      Belief Model Scales for Mammography Screening. Its aim (1) is to provide data
      about and (2) to assess Turkish women's attitudes and behaviours towards
      mammography. BACKGROUND: The proportion of women who have mammography is lower in
      Turkey. The Champion's Health Belief Model Scales for Mammography Screening
      Turkish version can be helpful to determine Turkish women's health beliefs,
      particularly about mammography. DESIGN: Cross-sectional design was used to
      collect survey data from Turkish women: classical measurement method. METHODS:
      The Champion's Health Belief Model Scales for Mammography Screening was
      translated from English to Turkish. Again, it was back translated into English.
      Later, the meaning and clarity of the scale items were evaluated by a bilingual
      group representing the culture of the target population. Finally, the tool was
      evaluated by two bilingual professional researchers in terms of content validity,
      translation validity and psychometric estimates of the validity and reliability.
      The analysis included a total of 209 Turkish women. The validity of the scale was
      confirmed by confirmatory factor analysis and criterion-related validity testing.
      RESULTS: The Champion's Health Belief Model Scales for Mammography Screening
      aligned to four factors that were coherent and relatively independent of each
      other. There was a statistically significant relationship among all of the
      subscale items: the positive and high correlation of the total item test score
      and high Cronbach's alpha. The scale has a strong stability over time: the
      Champion's Health Belief Model Scales for Mammography Screening demonstrated
      acceptable preliminary values of reliability and validity. CONCLUSION: The
      Champion's Health Belief Model Scales for Mammography Screening is both a
      reliable and valid instrument that can be useful in measuring the health beliefs
      of Turkish women. RELEVANCE TO CLINICAL PRACTICE: It can be used to provide data
      about healthcare practices required for mammography screening and breast cancer
      prevention. This scale will show nurses that nursing intervention planning is
      essential for increasing Turkish women's participation in mammography screening.

PMID- 24028177
TI  - Synthesis of 2,5-asymmetrically substituted 3,4-diaminothieno[2,3-b]thiophenes by
      domino reaction.
AB  - A convenient one pot synthesis of 2,5-asymmetrically substituted thieno[2,3
      b]thiophenes is developed. The method is based on consecutive domino reactions
      (SN2 reaction -> Thorpe-Ziegler reaction) using malononitrile and carbon
      disulfide as starting materials with the generation of potassium 2,2
      dicyanoethene-1,1-bis(thiolate) in a solution. The high yield of the target
      thienothiophenes was achieved using the Ziegler dilution effect. 

PMID- 24028179
TI  - Development of new formulation and its evaluation by capillary electrophoresis of
      tablets containing tramadol hydrochloride and paracetamol.
AB  - CONTEXT: A quick and efficient method to eliminate pain is combining
      complementary action and substances with synergic effect. Such an association is
      the one between tramadol hydrochloride and paracetamol, in which the rapid
      reaction time of the paracetamol is combined with the long-term effect of the
      tramadol hydrochloride. OBJECTIVE: Our aim was to develop and characterize
      alternative tablet formulations containing tramadol hydrochloride 37.5 mg and
      paracetamol 325 mg with different excipients in different ratio, and also the
      development of a new electrophoretic method for the quantitative determination of
      the active substances. MATERIALS AND METHODS: The tablets were evaluated for
      physical characteristics (weight, thickness, diameter, mechanical strength,
      friability, disintegration time), drug content and dissolution following Ph.Eur.7
      and USP 35 guidelines. A new capillary electrophoretic method was developed for
      the determination of the two active substances. RESULTS: Capillary
      electrophoresis proved to be an efficient method for the determination of drug
      content and also for the dissolution profile. The two substances were separated
      based on the differences between their own electrophoretic mobilities, and
      determined in UV at two different wavelengths. CONCLUSIONS: Tablet formulation
      proved to be a significant factor in quality of tramadol
      hydrochloride/paracetamol tablets, as considerable differences between tablets
      containing different excipients were found; while capillary electrophoresis can
      be considered a useful alternative for the quantitative determination of tramadol
      hydrochloride/paracetamol combinations.

PMID- 24028178
TI  - Interleukin-27 gene delivery for modifying malignant interactions between
      prostate tumor and bone.
AB  - We have examined the role of a novel cytokine, interleukin-27 (IL-27), in
      mediating interactions between prostate cancer and bone. IL-27 is the most
      recently characterized member of the family of heterodimeric IL-12-related
      cytokines and has shown promise in halting tumor growth and mediating tumor
      regression in several cancer models, including prostate cancer. Prostate cancer
      is frequently associated with metastases to the bone, where the tumor induces a
      vicious cycle of communication with osteoblasts and osteoclasts to induce bone
      lesions, which are a significant cause of pain and skeletal-related events for
      patients, including a high fracture risk. We describe our findings in the effects
      of IL-27 gene delivery on prostate cancer cells, osteoblasts, and osteoclasts at
      different stages of differentiation. We applied the IL-27 gene delivery protocol
      in vivo utilizing sonoporation (sonodelivery) with the goal of treating and
      reducing the growth of prostate cancer at a bone metastatic site in vivo. We used
      a new model of immune-competent prostate adenocarcinoma and characterized the
      tumor growth reduction, gene expression, and effector cellular profiles. Our
      results suggest that IL-27 can be effective in reducing tumor growth, can help
      normalize bone structure, and can promote enhanced accumulation of effector cells
      in prostate tumors. These results are promising, because they are relevant to
      developing a novel IL-27-based strategy that can treat both the tumor and the
      bone, by using this simple and effective sonodelivery method for treating
      prostate tumor bone metastases.

PMID- 24028180
TI  - Comparison of clinical characteristics in patients with obesity hypoventilation
      syndrome and obese obstructive sleep apnea syndrome: a case-control study.
AB  - INTRODUCTION: Obesity hypoventilation syndrome (OHS) can be overlooked unless
      clinicians have a high index of suspicion. The present case-control study aimed
      to compare characteristics of patients with OHS and obese obstructive sleep apnea
      syndrome (OSAS), and to identify determinants of hypercapnia in OSAS patients.
      METHODS: Demographic and anthropometric features, pulmonary function tests, blood
      gas analysis and sleep parameters of 59 OHS patients were compared to 295 body
      mass index-matched OSAS patients. RESULTS: The rate of hypertension (67.8% vs
      53.2%, respectively, P=0.027) was higher in OHS than OSAS group. In OHS patients,
      FVC (%) (P<0.0001), FEV1 (%) (P=0.001) and PaO2 (P<0.0001) were lower, whereas
      PaCO2 and HCO3 levels were increased (P<0.0001). Daytime sleepiness was more
      frequent (89.8% vs 68.5%, respectively, P=0.002), and Epworth sleepiness scores
      were higher (14.0 vs 11.9, respectively, P=0.021) in OHS than OSAS patients. In
      polysomnography, lowest and mean SpO2 were decreased, and sleep time with SpO2
      <90% was increased in patients with OHS (P<0.0001). Multivariate analysis showed
      that hypercapnia was associated independently with HCO3 (P<0.0001) and daytime
      SaO2 (P=0.003). Besides, HCO3 level >= 27 mEq/L had a sensitivity of 88.1% and
      specificity of 73.1%, and SaO2 <= 95% had a sensitivity of 64.4% and specificity
      of 73.9% for identifying OHS. CONCLUSION: It was shown that OHS patients have
      increased rate of hypertension, daytime sleepiness and HCO3 , and decreased lung
      functions and PaO2 levels than OSAS patients. The present results support that
      elevated bicarbonate levels and decreased oxygen saturations in obese OSAS
      patients should prompt clinicians to predict OHS.

PMID- 24028182
TI  - Breastfeeding and pain relief in full-term neonates during immunization
      injections: a clinical randomized trial.
AB  - BACKGROUND: The aim of this study was to examine the effect of breastfeeding on
      pain relief in full-term neonates during injection of hepatitis B vaccine.
      METHODS: This was a randomized clinical trial. A sample of full-term neonates was
      randomly allocated into two groups: the experimental group and the control group.
      Neonates in the experimental group were breastfed two minutes before, during, and
      after the hepatitis B immunization and the control group were held in mothers'
      arms but not fed. Pain was assessed using the Douleur Aigue du Nouveau-ne (DAN)
      scale measuring facial expressions, limb movements and vocal expressions. The
      assessments were carried out after hepatitis B immunization. RESULTS: One hundred
      thirty healthy full-term neonates were studied (65 in the experimental group and
      65 in the control group). Gestational age, birth weight, Apgar score and gender
      did not differ between the two groups. The mean total pain score as measured by
      the DAN scale was 3.52 (SD = 1.37) for the experimental group and it was 6.78 (SD
      = 1.69) for the controls indicating a significant lower pain score for the
      experimental group (P<0.001). Also, there were significant differences for the
      three measures of DAN scale that are facial expressions, limb movements and vocal
      expression, between the two study groups (P<0.001). CONCLUSION: The findings
      confirm that breastfeeding reduces pain and is effective way for pain relief
      during hepatitis B vaccine injection. TRIAL REGISTRATION: IRCT201104166206N1.

PMID- 24028181
TI  - How immunosuppressive therapy affects T cells from kidney transplanted patients
      of different age: the role of latent cytomegalovirus infection.
AB  - The average age of patients receiving renal transplantation is increasing as
      programmes have been established which support the donation of organs from
      elderly donors to older recipients. Little is known about the effect of
      immunosuppressive therapy on the immune system of older patients. In this study,
      T cell function and the composition of the T cell repertoire were analysed in
      immunosuppressed renal transplant recipients of different age and cytomegalovirus
      (CMV) status in comparison to age- and CMV-matched controls. Independent of age
      and CMV status, the production of interleukin (IL)-2 and interferon (IFN)-gamma
      by T cells was decreased in the patient groups and autologous serum from patients
      was capable of inhibiting the proliferation of CD3+ T cells. CXCR5 expression on
      T cells was increased in patients versus controls reflecting reduced endogenous
      IL-2 signalling under immunosuppressive therapy. In CMV-seronegative patients
      kidney transplantation and immunosuppressive therapy did not induce changes in
      the CD8+ T cell pool, but there was a moderate increase in CD4+CD28- effector T
      cells when compared to age-matched controls. In contrast, latent CMV infection
      triggered a shift from early to late differentiated CD4+ and CD8+ T cells in
      patients and controls. This shift was most pronounced in elderly transplant
      patients under immunosuppressive therapy. In conclusion, our results demonstrate
      that immunosuppressive therapy following kidney transplantation is effective in
      patients older than 65 years. Latent CMV infection, however, accelerates age
      related changes in the T cell repertoire in elderly people under
      immunosuppressive therapy. These patients should therefore be monitored with
      special care.

PMID- 24028183
TI  - Second-generation everolimus-eluting stents compared to first-generation drug
      eluting stents in patients treated for multivessel disease.
AB  - OBJECTIVE: This study aimed to compare the safety and efficacy of everolimus
      eluting stents (EES) to first-generation drug-eluting stents (DES) in multivessel
      disease (MVD). BACKGROUND: Second-generation EES have demonstrated superiority
      over first-generation DES for single-vessel disease, although the merits of EES
      in MVD are less established. METHODS: A cohort of 1,285 patients (3,124 lesions)
      with >= 2 diseased vessels were treated with either first-generation DES (n =
      1,002) or EES (n = 283). The rates of death, myocardial infarction, target lesion
      revascularization, target vessel revascularization, definite stent thrombosis,
      and major adverse cardiac events (MACE), defined as the combined incidence of
      target vessel revascularization, death, and non-fatal myocardial infarction, were
      compared at 1 year. RESULTS: Baseline characteristics were similar except for a
      lower left ventricular ejection fraction and a lower incidence of stable angina
      pectoris in the first-generation DES group (P = 0.001 and 0.013, respectively).
      At 1 year, the MACE rate was lower in the EES group (9.5P% vs. 15.7%; P = 0.01).
      Multivariable analysis demonstrated that EES use predicted a higher chance of
      freedom from MACE at 1 year (hazard ratio 0.58 [0.38-0.87]; P = 0.009; 95%
      confidence interval). CONCLUSIONS: The use of EES in patients with MVD is safe
      with signals for improved effectiveness compared to first-generation DES.
      Randomized trials comparing new-generation DES to coronary artery bypass grafting
      surgery are warranted.

PMID- 24028184
TI  - Exploring smooth muscle phenotype and function in a bioreactor model of abdominal
      aortic aneurysm.
AB  - BACKGROUND: Vascular smooth muscle cells (SMC) are central to arterial structure
      and function yet their involvement in the progression of abdominal aortic
      aneurysm (AAA) disease is not well studied. The progressive and silent nature of
      AAA in man essentially restricts research to the use of "end-stage" tissue
      recovered during surgical repair. This study aimed to generate an ex vivo model
      of AAA using protease-treated porcine carotid arteries maintained in a novel
      bioreactor, and to compare the structural and functional changes in SMC cultured
      from the recovered vessels with those from human tissue acquired at elective
      surgical repair. METHODS: Freshly isolated porcine arteries were pretreated with
      collagenase and/or elastase before culturing under flow in a bioreactor for 12
      days. Human end-stage aneurysmal tissue and saphenous veins from age-matched
      controls were collected from patients undergoing surgery. SMC were cultured and
      characterised (immunocytochemistry, measurement of spread cell area) and assessed
      functionally at the level of proliferation (cell-counting) and matrix
      metalloproteinase (MMP) secretion (gelatin zymography). Cellular senescence was
      investigated using beta-galactosidase staining and apoptosis was quantified using
      a fluorescence-based caspase 3 assay. RESULTS: Co-expression of alpha-smooth
      muscle actin and smooth muscle myosin heavy chain confirmed all cell populations
      as SMC. Porcine SMC harvested and cultivated after collagenase/elastase
      pretreatment displayed a prominent "rhomboid" morphology, increased spread area
      (32%, P < 0.01), impaired proliferation (47% reduction, P < 0.05), increased
      senescence (52%, P < 0.001), susceptibility to apoptosis and reduced MMP-2
      secretion (60% decrease, P < 0.01) compared with SMC from vehicle, collagenase or
      elastase pre-treated vessels. Notably, these changes were comparable to those
      observed in human AAA SMC which were 2.4-fold larger than non-aneurysmal SMC (P <
      0.001) and exhibited reduced proliferation (39% reduction, P < 0.001), greater
      apoptosis (4-fold increase, P < 0.001), and increased senescence (61%, P < 0.05).
      CONCLUSIONS: Combined collagenase/elastase exposure of porcine artery maintained
      in a bioreactor under flow conditions induced a SMC phenotype characteristic of
      those cultured from end-stage AAA specimens. This model has potential and
      versatility to examine temporal changes in SMC biology and to identify the
      molecular mechanisms leading to early aberrancies in SMC function. In the longer
      term this may inform new targets to maintain aortic SMC content and drive cells
      to a "reparative" phenotype at early stages of the disease.

PMID- 24028185
TI  - Neuropsychological and neurobehavioral outcome following childhood arterial
      ischemic stroke: attention deficits, emotional dysregulation, and executive
      dysfunction.
AB  - OBJECTIVES: To investigate neuropsychological and neurobehavioral outcome in
      children with arterial ischemic stroke (AIS). BACKGROUND: Childhood stroke can
      have consequences on motor, cognitive, and behavioral development. We present a
      cross-sectional study of neuropsychological and neurobehavioral outcome at least
      one year poststroke in a uniquely homogeneous sample of children who had
      experienced AIS. METHOD: Forty-nine children with AIS aged 6 to 18 years were
      recruited from a specialist clinic. Neuropsychological measures of intelligence,
      reading comprehension, attention, and executive function were administered. A
      triangulation of data collection included questionnaires completed by the
      children, their parents, and teachers, rating behavior, executive functions, and
      emotions. KEY FINDINGS: Focal neuropsychological vulnerabilities in attention
      (response inhibition and dual attention) and executive function were found,
      beyond general intellectual functioning, irrespective of hemispheric side of
      stroke. Difficulties with emotional and behavioral regulation were also found.
      Consistent with an "early plasticity" hypothesis, earlier age of stroke was
      associated with better performance on measures of executive function.
      CONCLUSIONS: A significant proportion of children poststroke are at long-term
      risk of difficulties with emotional regulation, executive function, and
      attention. Data also suggest that executive functions are represented in
      widespread networks in the developing brain and are vulnerable to unilateral
      injury.

PMID- 24028186
TI  - Minimal intestinal epithelial cell toxicity in response to short- and long-term
      food-relevant inorganic nanoparticle exposure.
AB  - Toxicity of commercial nanoparticles of titania, silica, and zinc oxides is being
      investigated in this in vitro study. Particles of these compositions are found in
      many food items, and thus this study is directed toward particle behavior in
      simulated digestion media and their interaction with intestinal epithelial cell
      line C2BBe1, a clone of Caco-2 cells, originally isolated from a human colon
      cancer. Even though the primary particle size of all three particles was below 50
      nm, the particles appeared as aggregates in culture media with a negatively
      charged surface. In the presence of pepsin (pH 2), the charge on the titania
      became positive, and silica was almost neutral and aggregated extensively,
      whereas ZnO dissolved. For silica and titania, treatment with simulated
      intestinal digestive solution led to a strongly negatively charged surface and
      particle sizes approaching values similar to those in media. On the basis of
      infrared spectroscopy, we concluded that the surface of silica and titania was
      covered with bile salts/proteins after this treatment. Transmission electron
      microscopy indicated that the C2BBe1 cells internalized all three particles.
      Toxicity assays included investigation of necrosis, apoptosis, membrane damage,
      and mitochondrial activity. Titania and SiO2 particles suspended in media at
      loading levels of 10 MUg/cm2 exhibited no toxicity. With ZnO at the same loading
      level, mild toxicity was observed based only on the LDH assay and decrease of
      mitochondrial activity and not necrosis or apoptosis. Titania particles exposed
      to the simulated digestion media exhibited mild toxicity based on decrease of
      mitochondrial activity, likely due to transport of toxic bile salts via
      adsorption on the particle surface.

PMID- 24028187
TI  - Meeting report: 2013 Peripheral Nerve Society Biennial Meeting, Saint-Malo,
      France, June 29-July 3, 2013.

PMID- 24028188
TI  - Cdc42 GTPases facilitate TNF-alpha-mediated secretion of CCL2 from peripheral
      nerve microvascular endoneurial endothelial cells.
AB  - Trafficking of autoreactive leukocytes across the blood-nerve barrier and into
      peripheral nerves is an early pathological hallmark of Guillain-Barre syndrome
      (GBS). Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine,
      promotes transendothelial migration by upregulating endothelial expression of
      inflammatory mediators, including CCL2, a chemokine implicated in GBS. We sought
      to determine the mechanism by which TNF-alpha induces expression and secretion of
      CCL2 from peripheral nerve microvascular endoneurial endothelial cells (PNMECs).
      Expression of CCL2 mRNA and protein in quiescent PNMEC cultures was minimal. In
      contrast, cultures treated with TNF-alpha exhibited increased CCL2 mRNA and
      protein content, as well as protein secretion. Simvastatin significantly
      attenuated TNF-alpha-induced CCL2 secretion without affecting CCL2 mRNA or
      protein expression. Co-incubation with geranylgeranyl pyrophosphate, but not
      farnesyl pyrophosphate, prevented the effect of simvastatin. By comparison,
      inhibiting protein isoprenylation with GGTI-298, but not FTI-277, mimicked the
      effect of simvastatin and significantly attenuated transendothelial migration in
      vitro. Inhibition of the monomeric GTPase Cdc42, but not Rac1 or RhoA-C,
      attenuated TNF-alpha-mediated CCL2 secretion. TNF-alpha-mediated trafficking of
      autoreactive leukocytes into peripheral nerves during GBS may proceed by a
      mechanism that involves Cdc42-facilitated secretion of CCL2. 

PMID- 24028189
TI  - In vivo peripheral nervous system insulin signaling.
AB  - Alterations in peripheral nervous system (PNS) insulin support may contribute to
      diabetic neuropathy (DN); yet, PNS insulin signaling is not fully defined. Here,
      we investigated in vivo insulin signaling in the PNS and compared the insulin
      responsiveness to that of muscle, liver, and adipose. Non-diabetic mice were
      administered increasing doses of insulin to define a dose-response relationship
      between insulin and Akt activation in the dorsal root ganglion (DRG) and sciatic
      nerve. Resulting EC50 doses were used to characterize the PNS insulin signaling
      time course and make comparisons between insulin signaling in the PNS and other
      peripheral tissues (i.e., muscle, liver, and adipose). The results demonstrate
      that the PNS is responsive to insulin and that differences in insulin signaling
      pathway activation exist between PNS compartments. At a therapeutically relevant
      dose, Akt was activated in the muscle, liver, and adipose at 30 min, correlating
      with the changes in blood glucose levels. Interestingly, the sciatic nerve showed
      a similar signaling profile as insulin-sensitive tissues; however, there was not
      a comparable activation in the DRG or spinal cord. These results present new
      evidence regarding PNS insulin signaling pathways in vivo and provide a baseline
      for studies investigating the contribution of disrupted PNS insulin signaling to
      DN pathogenesis. 

PMID- 24028191
TI  - Correlation of nerve ultrasound, electrophysiological, and clinical findings in
      post Guillain-Barre syndrome.
AB  - We aimed to correlate functional disability, electrophysiology, and nerve
      ultrasound in patients after Guillain-Barre syndrome (GBS). Seventy-five healthy
      controls and 41 post-GBS patients (mean 3.4 years, SD +/- 2.91 years after onset)
      underwent clinical, sonographic, and electrophysiological evaluation. Compared to
      healthy controls, the post-GBS patients showed: (1) a mean Rasch-built Overall
      Disability Scale score of 31.8 (SD +/- 11.6), modified Rasch-built fatigue
      severity scale score of 15.6 (SD +/- 3.2), Medical Research Council sum score of
      22 (SD +/- 5.6); (2) electrophysiological signs of permanent axonal loss in the
      majority of the peripheral nerves; (3) sonographical evidence of higher cross
      sectional area values (CSA) of the ulnar (elbow, p < 0.001), radial (spiral
      groove, p < 0.001), tibial nerve (popliteal fossa, p < 0.001) and brachial plexus
      (supraclavicular space, p < 0.001). No correlation between sonographic and
      electrophysiological findings was found. Neither nerve ultrasound nor
      electrophysiology correlated with muscle strength, overall disability, and
      fatigue scale. Compared to healthy controls, post-GBS patients had significant
      functional disability. Despite significant abnormalities in both
      electrophysiology and ultrasound compared to healthy controls, neither
      electrophysiology nor nerve ultrasound correlated with functional disability of
      these patients. 

PMID- 24028190
TI  - Functional recovery following peripheral nerve injury in the transgenic Thy1-GFP
      rat.
AB  - Transgenic mice have been previously used to assess nerve regeneration following
      peripheral nerve injury. However, mouse models are limited by their small caliber
      nerves, short nerve lengths, and their inability to fully participate during
      behavioral assessments. The transgenic Thy1 GFP rat is a novel transgenic rat
      model designed to assess regeneration following peripheral nerve injury. However,
      return of functional and behavioral recovery following nerve injury has not yet
      been evaluated in these rats. In this study, we ask whether differences in
      anatomy, recovery of locomotion, myological, and histomorphological measures
      exist between transgenic Thy1 GFP rats when compared to wild type (WT) Sprague
      Dawley rats following unilateral sciatic nerve injury. We found that both motor
      and sensory neuronal architecture, overground and skilled locomotion, muscle
      force, motor unit number estimation (MUNE) and wet muscle weights, and
      histomorphometric assessments are similar between both genetic phenotypes.
      Overall, these data support the use of the transgenic Thy1-GFP rat in experiments
      assessing functional and behavioral recovery following nerve injury and repair. 

PMID- 24028192
TI  - Impairment and disability in 20 CIDP patients according to disease activity
      status.
AB  - Twenty patients with chronic inflammatory demyelinating polyradiculoneuropathy
      (CIDP) meeting the EFNS/PNS criteria were examined in order to assess
      differences/similarities between the various grading systems according to CIDP
      disease activity status (CDAS). A principal component (PC) analysis and the
      correlations between the following scores were performed: Neurological Symptom
      Score; MRC sum score; Neurological Impairment Score; Hammersmith Functional Motor
      Scale; Inflammatory Neuropathy Cause and Treatment (INCAT) Sensory Sum Score;
      Overall Disability Sum Score; INCAT Disability Score; Rasch-built Overall
      Disability Scale. Our analysis outlined two main sets of scales, with high
      influence in the top two PCs. The first PC that best explained the variability
      within the cohort consisted of CDAS, general disability scores and motor scores;
      these parameters were also strongly correlated amongst each other. The second PC
      explained less the variability and consisted mainly of sensory scores and disease
      duration; these parameters did not correlate with the scores of the first PC or
      with the CDAS. Our findings suggest separating screening for motor and sensory
      deficits when evaluating CIDP patients, as only the motor scores correlate with
      CDAS. 

PMID- 24028193
TI  - Progression in idiopathic, diabetic, paraproteinemic, alcoholic, and B12
      deficiency neuropathy.
AB  - We determined prospectively the clinical and electrophysiological progression of
      idiopathic, diabetic, paraproteinemic, alcoholic, and B12 deficiency neuropathy
      in 606 subjects over 3 years. We hypothesized that idiopathic peripheral
      neuropathy would demonstrate slower progression when compared with other
      etiologies. Laboratory assessments were used to determine the etiology of
      peripheral neuropathy at baseline and after 3 years. When compared with
      peripheral neuropathy related to type 1 or type 2 diabetes mellitus, subjects
      with idiopathic peripheral neuropathy progressed much slower, but demonstrated
      similar rates of progression to that of the other groups. Overall, detectable
      progression was minimal over 3 years. After 3 years, only 3% of cases of
      idiopathic peripheral neuropathy had any potentially identifiable causes
      discovered. Clinical and electrophysiological detection of very slow progression
      for these five types of peripheral neuropathy is possible using currently
      established clinical scales and standard electrophysiological techniques. 

PMID- 24028194
TI  - Two novel MPZ mutations in Chinese CMT patients.
AB  - To investigate the myelin protein zero (MPZ) gene mutation and related clinical
      features in Chinese Charcot-Marie-Tooth (CMT) patients, we screened the coding
      sequence of MPZ in 70 unrelated CMT index patients after excluding the PMP22
      duplication, Cx32 and MFN2 mutations. We found four different missense mutations:
      c.194C>T, c.242A>T, c.371C>T, and c.419C>G. The frequency of MPZ mutation was
      approximately 4.35% of the total, 3.08% of CMT1, and 6% of CMT2. Mutations
      c.242A>T and c.419C>G are novel. The mutation c.242A>T exhibited late onset and
      rapidly progressive CMT2 phenotype. The mutation c.419C>G exhibited relatively
      late onset and slowly progressive CMT1 phenotype. 

PMID- 24028195
TI  - CMT4D (NDRG1 mutation): genotype-phenotype correlations.
AB  - Charcot-Marie-Tooth (CMT) disease is a heterogeneous condition with a large
      number of clinical, electrophysiological and pathological phenotypes. More than
      40 genes are involved. We report a child of gypsy origin with an autosomal
      recessive demyelinating phenotype. Clinical data, familial history, and
      electrophysiological studies were in favor of a CMT4 sub-type. The characteristic
      N-Myc downstream-regulated gene 1 (NDRG1) mutation responsible for this CMT4D
      phenotype was confirmed: p.R148X. The exact molecular function of the NDRG1
      protein has yet to be elucidated. 

PMID- 24028196
TI  - Serial nerve conduction studies show changes in the axonal excitability of motor
      and sensory nerves in Fisher syndrome.

PMID- 24028197
TI  - Corneal confocal microscopy in patients with oxaliplatin-induced peripheral
      neuropathy.

PMID- 24028198
TI  - Tunable synthesis of 3-acyl-2-naphthols and 3-substituted isocoumarins via Jones
      reagent promoted cascade reactions of 2-(4-hydroxy-but-1-ynyl)benzaldehydes.
AB  - Novel and efficient synthesis of 3-acyl-2-naphthols and 3-substituted
      isocoumarins via the tunable cascade reactions of 2-(4-hydroxy-but-1
      ynyl)benzaldehydes have been developed. Treatment of 2-(4-hydroxy-but-1
      ynyl)benzaldehydes with 0.7 equiv of Jones reagent in CH3CN and subsequent
      purification through column chromatography on silica gel pre-eluted with Et3N
      afforded 3-acyl-2-naphthols with high efficiency. When the same substrates were
      treated with 3 equiv of Jones reagents in acetone, on the other hand, 3
      substituted isocoumarins could be obtained in good yields. 

PMID- 24028199
TI  - Olefin hydroaryloxylation catalyzed by pincer-iridium complexes.
AB  - Aryl alkyl ethers, which are widely used throughout the chemical industry, are
      typically produced via the Williamson ether synthesis. Olefin hydroaryloxylation
      potentially offers a much more atom-economical alternative. Known acidic
      catalysts for hydroaryloxylation, however, afford very poor selectivity. We
      report the organometallic-catalyzed intermolecular hydroaryloxylation of
      unactivated olefins by iridium "pincer" complexes. These catalysts do not operate
      via the hidden Bronsted acid pathway common to previously developed transition
      metal-based catalysts. The reaction is proposed to proceed via olefin insertion
      into an iridium-alkoxide bond, followed by rate-determining C-H reductive
      elimination to yield the ether product. The reaction is highly chemo- and
      regioselective and offers a new approach to the atom-economical synthesis of
      industrially important ethers and, potentially, a wide range of other oxygenates.

PMID- 24028200
TI  - Familial summer-type hypersensitivity pneumonitis in Japan: two case reports and
      review of the literature.
AB  - BACKGROUND: Hypersensitivity pneumonitis is defined as an allergic lung disease
      that occurs in response to inhalation of fungal antigens, bacterial antigens,
      chemicals, dusts, or animal proteins. The incidence of summer-type
      hypersensitivity pneumonitis is higher in the summer season, especially in Japan,
      due to the influence of the hot and humid environment and the common style of
      wood house or old concrete condominiums. CASE PRESENTATION: The present report
      describes a case of a middle-aged married couple who lived in the same house and
      who simultaneously suffered from summer-type hypersensitivity pneumonitis. This
      report analyzes these two cases in terms of environmental research and its
      microbiological, radiological, and pathological aspects. This case report is
      followed by a review of family occurrences of summer-type hypersensitivity
      pneumonitis from 22 studies with a total of 49 patients (including the two
      present cases) in Japan. CONCLUSION: Summer-type hypersensitivity pneumonitis may
      be unrecognized and misdiagnosed as pneumonia or other respiratory diseases. A
      greater understanding of the clinical, pathologic, and environmental features of
      summer-type hypersensitivity pneumonitis might help improve diagnosis and
      delivery of appropriate management for this condition.

PMID- 24028202
TI  - Different human gut models reveal the distinct fermentation patterns of
      Arabinoxylan versus inulin.
AB  - Different in vitro models have been developed to assess how food compounds affect
      the human gut microbiota. Using two such models (SHIME(R) and TIM-2), we compared
      how long-chain arabinoxylan (LC-AX), a wheat-derived potentially prebiotic fiber,
      and inulin (IN), a well-established prebiotic compound, modulate SCFA production
      and bifidobacteria composition. While both the SHIME and TIM-2 differ in
      experimental design, they both demonstrated that LC-AX and IN specifically
      increased the health-promoting metabolites propionate and butyrate, respectively.
      Furthermore, LC-AX stimulated Bifidobacterium longum, while IN stimulated other
      bifidobacteria including Bifidobacterium adolescentis. The SHIME experiment also
      revealed that effects of LC-AX were more persistent during the 2-week wash-out
      period. These results confirm a recent in vivo study, during which humanized rats
      were treated with the same LC-AX/IN. In conclusion, results from different human
      gut models suggest that, besides IN, LC-AX are promising prebiotic candidates
      with high specificity toward Bifidobacterium longum and a selective propionate
      increase. 

PMID- 24028203
TI  - Assessment of volume status and arterial stiffness in chronic kidney disease.
AB  - AIM: There is limited information about arterial stiffness in chronic kidney
      disease (CKD) which is an independent risk factor for cardiovascular events.
      Pulse wave velocity (PWV), augmentation index (AIx) are using to determine
      arterial stiffness. We aimed to study PWV, AIx, volume status in patients with
      stage 3B-5 CKD and continuous ambulatory peritoneal dialysis (CAPD). METHODS:
      Sixty-six stage 3B-5 CKD patients, 21 CAPD patients, 34 healthy controls were
      included. Pulse wave velocity, AIx, volume status was evaluated by Mobil-O
      Graph(r), and bioimpedance spectroscopy, respectively. RESULTS: The Median PWV
      was 7.5 m/s in CKD, 6.2 m/s in CAPD, 5.9 m/s in healthy controls, and while PWV
      was found to have increased significantly in CKD patients (p = 0.002), the Alx
      values were similar in all groups. The median extracellular fluid excess was
      higher in both the CKD and, CAPD patients when compared with healthy controls
      (1.26 and 1.21 L, respectively). Overhydration was more prevalent in CKD and CAPD
      patients (p < 0.001). Age, central systolic blood pressure, body mass index, fat
      mass, overhydration, CKD, eGFR were the major determinants of PWV. CONCLUSION:
      Increased PWV was found in stage 3B-5 CKD patients. Overhydration may contribute
      this increment.

PMID- 24028201
TI  - Efficacy of strength and aerobic exercise on patient-reported outcomes and
      structural changes in patients with knee osteoarthritis: study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Despite an extensive literature on treatment interventions for
      patients with knee osteoarthritis, studies comparing the efficacy of different
      exercise interventions and living the life as usual on quality of life, cartilage
      quality and cost-effectiveness are lacking. The aim of the present study is to
      compare the efficacy of two different exercise programs compared to a control
      group in individuals with established radiographic and symptomatic knee
      osteoarthritis on self-reported knee-related quality of life, knee pain, physical
      function, and cartilage quality. METHODS/DESIGN: A three-armed randomized
      controlled trial involving two exercise interventions and a control group of
      individuals doing as they usually do is described. The patients will have mild to
      moderate radiographic osteoarthritis according to the Kellgren and Lawrence
      classification (grade 2-3), and fulfill the American College of Rheumatology
      clinical criteria, be aged between 45 and 65 years, and have no other serious
      physical or mental illnesses. The patients will be randomly allocated to a
      strength exercise group; a cycling group, or a control group. The primary outcome
      is the Knee injury and Osteoarthritis Outcome Score knee-related quality of life
      subscale. Secondary outcomes include all five Knee Injury and Osteoarthritis
      Outcome Score subscales, morphological evaluation of cartilage including focal
      thickness, subchondral bone marrow edema, proteoglycan content and collagen
      degradation (measured using magnetic resonance imaging clinical sequences, T2
      mapping and T1rho), specific serum biomarkers, isokinetic muscle strength,
      maximal oxygen uptake, quality of life (EuroQol 5D), and self-efficacy (Arthritis
      Self-Efficacy Scale). A sample size calculation on the primary outcome showed
      that 207 individuals, 69 in each group, is needed to detect a clinically relevant
      difference of 10 points with 80% power and a significance level of 5%.
      Assessments will be conducted at baseline, 14 weeks, 1 year and 2 years post
      randomization. The interventions will be a 14 weeks exercise program. DISCUSSION:
      Although exercise therapy has been found to be effective in knee osteoarthritis,
      the knowledge of the underlying mechanisms for why exercise works is lacking.
      This study will contribute with knowledge on the efficacy of strength exercise
      versus cycling on patient-reported outcomes, cartilage quality and cost
      effectiveness. TRIAL REGISTRATION: Clinicaltrial.gov Identifier: NCT01682980.

PMID- 24028204
TI  - Expression of cytotoxic T-lymphocyte antigen 4 on CD4+ and CD8+ T cells is
      increased in acute lung injury.
AB  - Acute lung injury (ALI) is a severe form of diffuse lung disease, which imposes a
      substantial health burden all over the world. The immune system plays a key role
      in the development of ALI. The aim of the study was to investigate the expression
      of cytotoxic T-lymphocyte antigen 4 (CTLA4) in ALI. Levels of CTLA4 were tested
      on CD4+ and CD8+ T cells in 62 ALI cases and 75 healthy controls by flow
      cytometry. Data revealed that prevalence of CTLA4 on CD4+ T cells was
      significantly increased in ALI patients (3.7%+/-2.1%) than in controls (0.7%+/
      0.3%). Similarly, the proportion of CTLA4 on CD8+ T cells was also significantly
      elevated in cases (1.0%+/-0.4% versus 0.5%+/-0.1%, p<0.05). Further analysis
      showed that the frequency of CTLA4+CD4+ T cells was positively correlated with
      the score of Acute Physiology and Chronic Health Evaluation II (APACHE II)
      (p=0.0005). In addition, when investigating CTLA4 expression with ALI patient
      mortality, we observed that the level of CTLA4+CD4+ T cells in patients was
      higher at the time before death than at the time of recruitment (p=0.001). These
      data suggested that CTLA4 was involved in the pathogenesis and progression of ALI
      and could be used as a potential target for treating this disease. 

PMID- 24028205
TI  - Successful gene therapy in older Rpe65-deficient dogs following subretinal
      injection of an adeno-associated vector expressing RPE65.
AB  - Young Rpe65-deficient dogs have been used as a model for human RPE65 Leber
      congenital amaurosis (RPE65-LCA) in proof-of-concept trials of recombinant adeno
      associated virus (rAAV) gene therapy. However, there are relatively few reports
      of the outcome of rAAV gene therapy in Rpe65-deficient dogs older than 2 years of
      age. The purpose of this study was to investigate the success of this therapy in
      older Rpe65-deficient dogs. Thirteen eyes were treated in dogs between 2 and 6
      years old. An rAAV2 vector expressing the human RPE65 cDNA driven by the human
      RPE65 promoter was delivered by subretinal injection. Twelve of the 13 eyes had
      improved retinal function as assessed by electroretinography, and all showed
      improvement in vision at low lighting intensities. Histologic examination of five
      of the eyes was performed but found no correlation between electroretinogram
      (ERG) rescue and numbers of remaining photoreceptors. We conclude that functional
      rescue is still possible in older dogs and that the use of older Rpe65-deficient
      dogs, rather than young Rpe65-deficient dogs that have very little loss of
      photoreceptors, more accurately models the situation when treating human RPE65
      LCA patients.

PMID- 24028206
TI  - Thoracic epidural fentanyl has spinal cord analgesic effects.

PMID- 24028208
TI  - Increased urinary IgM excretion in patients with chest pain due to coronary
      artery disease.
AB  - BACKGROUND: Micro-albuminuria is a recognized predictor of cardiovascular
      morbidity and mortality in patients with coronary artery disease. We have
      previously reported, in diabetic and non-diabetic patients, that an increased
      urinary excretion of IgM is associated with higher cardiovascular mortality. The
      purpose of this study was to investigate the pattern of urinary IgM excretion in
      patients with acute coronary syndrome (ACS) and its correlation to cardiovascular
      outcome. METHODS: Urine albumin, and IgM to creatinine concentration ratios were
      determined in 178 consecutive patients presenting with chest pain to the
      Department of Emergency Medicine (ED) at the University Hospital of Lund. Fifty
      eight (23 female) patients had ACS, 55 (19 female) patients had stable angina
      (SA), and 65 (35 female) patients were diagnosed as non-specific chest pain (NS).
      RESULTS: Urine albumin and IgM excretions were significantly higher in patients
      with ACS (p = 0.001, and p = 0.029, respectively) compared to patients with NS
      chest pain. During the 2 years follow-up time, 40 (19 female) patients suffered a
      new major cardiovascular event (ACS, acute heart failure, stroke) and 5 (4 male/1
      female) patients died of cardiovascular cause. A high degree of albuminuria and
      IgM-uria significantly predicted cardiovascular mortality and morbidity (HR =
      2.89, 95% CI: 1.48 - 5.66, p = 0.002). Microalbuminuric patients (>=3 mg/mmol)
      with high IgM-uria (>=0.005 mg/mmol) had a 3-fold higher risk for cardiovascular
      new events compared to patients with low IgM-uria (RR = 3.3, 95% CI: 1.1 - 9.9, p
      = 0.001). CONCLUSION: In patients with chest pain, an increased urine IgM
      excretion, is associated with coronary artery disease and long-term
      cardiovascular complications. Measuring urine IgM concentration could have a
      clinical value in risk stratification of patients with ACS.

PMID- 24028209
TI  - Factors Influencing the twisting and untwisting properties of the left ventricle
      during normal pregnancy.
AB  - AIMS: During pregnancy, important hemodynamic changes occur, consistent with an
      increase in preload and decrease in afterload and systemic vascular resistance.
      The aim of the present study was to investigate the changes in left ventricular
      (LV) strain and rotational properties during the 3 trimesters of normal pregnancy
      and to examine the factors that drive these changes. METHODS AND RESULTS: Twenty
      seven pregnant women (29.7 +/- 6.9 years) and 11 age-matched nonpregnant controls
      (29.9 +/- 5.4 years) were evaluated. Conventional echocardiography and two
      dimensional speckle tracking imaging were performed at 8-12 (1st trimester), 21
      28 (2nd trimester), and 33-36 (3rd trimester) weeks of pregnancy. LV rotation,
      twist, untwisting rate, and circumferential strain were measured using the
      parasternal short-axis views at basal and apical levels. Global longitudinal
      strain was calculated from the LV apical views. Peak LV twist and peak untwisting
      rate increased significantly in the 3rd trimester of normal pregnancy (13.48 +/-
      2.90 degrees , 13.12 +/- 3.30 degrees , 16.83 +/- 3.61 degrees , P < 0.001; and 
      111.52 +/- 23.54 degrees /sec, -107.40 +/- 26.58 degrees /sec, -144.30 +/- 45.14
      degrees /sec, P < 0.001; in the 1st, 2nd, and 3rd trimester, respectively).
      Global longitudinal and circumferential strain of the apex decreased
      significantly from the 2nd trimester. An independent association was found
      between the change in LV twist and the change in LV end-systolic volume between
      the 1st and 3rd trimester. Peak untwisting rate at the 3rd trimester correlated
      significantly with peak twist and LV end-diastolic volume. CONCLUSIONS: During
      normal pregnancy, LV twist and peak untwisting rate increase in the 3rd trimester
      and correlate with end-systolic and end-diastolic volume, respectively.
      Circumferential strain of the apex and global longitudinal strain decrease from
      the 2nd trimester.

PMID- 24028211
TI  - The effects of verb retrieval therapy for people with non-fluent aphasia:
      evidence from assessment tasks and conversation.
AB  - Despite often impressive improvements on linguistic assessments, there is a lack
      of evidence of significant generalisation from impairment-focused aphasia therapy
      to everyday communication. The aim of the current study was to investigate the
      effect of a verb retrieval therapy across a range of levels of language
      production. Nine participants with chronic non-fluent stroke aphasia were
      recruited into this case series. Baseline assessment included naming a range of
      verbs (i.e., action verbs, semantically light verbs and personally relevant
      verbs) and sentence production. Multiple samples of conversation were collected
      from each participant and his/her partner. Consecutively failed verbs were
      divided across treatment and control sets; these sets were matched for salient
      psycholinguistic variables such as frequency, imageability and argument
      structure. A multi-component verb retrieval therapy was delivered, consisting of
      semantic feature analysis, gesture production and phonemic cueing. Following
      therapy, participants demonstrated significant and sustained gains in naming
      treated verbs; more modest effects were seen in untreated verbs. Mixed patterns
      of generalisation were evident in assessment of sentence production. In
      conversation, while group analysis suggested a lack of change, individual
      analyses indicated increased verb retrieval for three participants and
      qualitative changes related to the syntactic contexts of verbs retrieved. 

PMID- 24028210
TI  - Upregulation of M3 muscarinic receptor inhibits cardiac hypertrophy induced by
      angiotensin II.
AB  - BACKGROUND: M3 muscarinic acetylcholine receptor (M3-mAChR) is stably expressed
      in the myocardium, but its pathophysiological role remains largely undefined.
      This study aimed to investigate the role of M3-mAChR in cardiac hypertrophy
      induced by angiotensin II (Ang II) and elucidate the underlying mechanisms.
      METHODS: Cardiac-specific M3-mAChR overexpression transgenic (TG) mice and rat
      H9c2 cardiomyoblasts with ectopic expression of M3-mAChR were established. Models
      of cardiac hypertrophy were induced by transverse aortic constriction (TAC) or
      Ang II infusion in the mice in vivo, and by isoproterenol (ISO) or Ang II
      treatment of H9c2 cells in vitro. Cardiac hypertrophy was evaluated by
      electrocardiography (ECG) measurement, hemodynamic measurement and histological
      analysis. mRNA and protein expression were detected by real-time RT-PCR and
      Western blot analysis. RESULTS: M3-mAChR was upregulated in hypertrophic heart,
      while M2-mAChR expression did not change significantly. M3-mAChR overexpression
      significantly attenuated the increased expression of atrial natriuretic peptide
      and beta-myosin heavy chain induced by Ang II both in vivo and in vitro. In
      addition, M3-mAChR overexpression downregulated AT1 receptor expression and
      inhibited the activation of MAPK signaling in the heart. CONCLUSION: The
      upregulation of M3-mAChR during myocardial hypertrophy could relieve the
      hypertrophic response provoked by Ang II, and the mechanism may involve the
      inhibition of MAPK signaling through the downregulation of AT1 receptor.

PMID- 24028212
TI  - Patterns of help-seeking in women when problems arise in their sexual life: a
      discussion paper.
AB  - AIMS AND OBJECTIVES: To explore patterns of help-seeking in women who have sexual
      dysfunction and the implications for nursing practice. BACKGROUND: Female sexual
      dysfunction is a common problem that is under-reported and untreated. Barriers to
      help-seeking reported in existing literature relate to the perception among many
      women that sexual dysfunction is: part of the normal ageing process; not
      bothersome or does not exist; an issue that health professionals are reluctant to
      address; a taboo subject. However, little is known about patterns of help-seeking
      in women with sexual problems. This leaves a potential gap in nursing knowledge
      regarding appropriate, supportive strategies. DESIGN: Discursive inquiry framed
      theoretically by Vogel's model. METHODS: A literature review was undertaken by
      searching relevant databases. A combination of keywords was used to identify peer
      review papers relating to women's help-seeking behaviour for sexual dysfunction.
      Vogel's model was used as a framework to extract relevant information from the
      papers and structure the discussion. RESULTS: Vogel's model comprises four steps:
      encoding and interpreting, generating options, decision-making and evaluation of
      behaviour. Using this stepwise approach helped elucidate the complex mechanisms
      associated with help-seeking in a structured manner. The key issues associated
      with help-seeking intention are concerned with women's personal awareness of and
      interaction with the environment. CONCLUSIONS: Vogel's model offers a new
      approach to understanding the dynamics that underpin women's decisions to seek
      professional help when sexual concerns arise and also provides a useful framework
      for nurses to consider women's specific sexual concerns. RELEVANCE TO CLINICAL
      PRACTICE: Implications for nursing practice are focused on public awareness,
      women's empowerment and the provision of effective sexual health care. Because
      sexual dysfunction is a global phenomenon, it is likely that the discussion in
      this paper will be relevant to an international, nursing readership.

PMID- 24028214
TI  - Controlled attenuation parameter (CAP) for detection of hepatic steatosis in
      patients with chronic liver diseases: a prospective study of a native Korean
      population.
AB  - BACKGROUND: Controlled attenuation parameter (CAP) is a non-invasive method of
      measuring hepatic steatosis using a process based on transient elastography. We
      investigated the diagnostic accuracy of CAP in detecting hepatic steatosis in
      patients with chronic liver disease (CLD). METHODS: A total of 135 patients with
      CLD who underwent liver biopsy and CAP were consecutively enrolled in this
      prospective study. The performance of CAP for detection of hepatic steatosis
      compared with liver biopsy was calculated using area under receiver operating
      characteristics curves (AUROC). Steatosis was categorized into S0 (<5%), S1 (5
      33%), S2 (34-66%) and S3 (>66% of hepatocytes). RESULTS: Male gender predominated
      (n = 87, 64%) and the median age was 51 years. The aetiologies of CLD included
      non-alcoholic fatty liver disease (n = 56, 41.5%) and chronic viral hepatitis
      because of hepatitis B (n = 47, 34.8%) and C (n = 12, 8.9%). Steatosis
      repartition was: S0 31.1% (n = 42), S1 43.7% (n = 59), S2 18.5% (n = 25) and S3
      6.7% (n = 9) respectively. In the multivariate analysis, steatosis grade and body
      mass index were independently associated with CAP (all P < 0.001), whereas
      fibrosis stage and activity grade were not. The AUROCs of CAP were 0.885 for >=S1
      (sensitivity 73.1%, specificity 95.2%), 0.894 for >=S2 (sensitivity 82.4%,
      specificity 86.1%) and 0.800 for S3 (sensitivity 77.8%, specificity 84.1%). The
      optimal cut-off CAP values that maximized the Youden index were 250 dB/m (>=S1),
      299 dB/m (>=S2), and 327 dB/m (=S3) respectively. CONCLUSIONS: Our data showed
      that CAP had high diagnostic accuracy for detecting hepatic steatosis in patients
      with CLD and suggested that CAP is also applicable for Asian patients.

PMID- 24028215
TI  - Parenting, corpus callosum, and executive function in preschool children.
AB  - In this longitudinal population-based study (N = 544), we investigated whether
      early parenting and corpus callosum length predict child executive function
      abilities at 4 years of age. The length of the corpus callosum in infancy was
      measured using postnatal cranial ultrasounds at 6 weeks of age. At 3 years, two
      aspects of parenting were observed: maternal sensitivity during a teaching task
      and maternal discipline style during a discipline task. Parents rated executive
      function problems at 4 years of age in five domains of inhibition, shifting,
      emotional control, working memory, and planning/organizing, using the Behavior
      Rating Inventory of Executive Function-Preschool Version. Maternal sensitivity
      predicted less executive function problems at preschool age. A significant
      interaction was found between corpus callosum length in infancy and maternal use
      of positive discipline to determine child inhibition problems: The association
      between a relatively shorter corpus callosum in infancy and child inhibition
      problems was reduced in children who experienced more positive discipline. Our
      results point to the buffering potential of positive parenting for children with
      biological vulnerability. 

PMID- 24028216
TI  - Spiroergometric parameters at maximal exercise testing assessed functional
      respiratory impairment in asbestos-induced fibrosis.
AB  - INTRODUCTION: Exercise intolerance is typical for asbestosis. We examined the
      correlation of spiroergometric parameters with severity of asbestosis according
      to the International Labour Office (ILO) classification. Patients were compared
      to a healthy control group. OBJECTIVES: Nineteen consecutive male patients with
      compensated asbestosis and 24 healthy subjects were examined. METHODS: All
      participants underwent pulmonary functional testing including maximal
      cardiopulmonary exercise testing (CPET). Results were compared to those of
      healthy subjects; the correlation to disease status was investigated. RESULTS:
      Significantly lower VCin , FVC, FEV1 , MEF50 , TLC and PaO2 at rest (P<0.001)
      were observed in asbestosis patients. Lower peak (weight-related) work rate (WR,
      WR/kg), (weight-related) oxygen uptake (V'O2 , V'O2 /kg), oxygen pulse (V'O2
      /hr), ventilation volume (V'E ), carbon dioxide output (V'CO2 ) and blood lactate
      was associated (P<0.001) with more severe asbestosis according to the ILO
      classification. Significant positive correlations (P<0.001) were seen for
      alveolar-arterial oxygen difference [P(A-a)O2 ] and PaCO2 . Multiple regression
      analysis revealed that asbestosis was the only significant factor associated with
      the spiroergometric parameters (P<0.001). A reduction of V'O2 , V'O2 /kg, V'O2
      /hr, V'E , or V'CO2 at identical submaximal workload could neither be detected
      among the asbestosis severity nor in comparison to healthy subjects. Only the
      respiratory frequency was depending on severity of asbestosis. CONCLUSIONS: The
      severity of asbestosis correlates with maximal WR, V'O2 , V'O2 /hr, V'E and gas
      exchange. At identical workload the discrimination between patients and controls
      was only possible concerning the respiratory frequency. For detection of
      limitations in asbestosis patients, maximal CPET is recommended.

PMID- 24028218
TI  - Ruthenium-catalyzed C-H activation/cyclization for the synthesis of
      phosphaisocoumarins.
AB  - An efficient and cost-effective ruthenium-catalyzed oxidative cyclization of
      phosphonic acid monoesters or phosphinic acids with alkynes has been developed
      for the synthesis of a wide range of phosphaisocoumarins in good to excellent
      yields under aerobic conditions. A multitude of arylphosphonic acid monoesters
      and arylphosphinic acids having electron-donating and -withdrawing groups were
      oxidatively cyclized. Various diarylacetylenes, dialkylacetylenes, and
      alkylarylacetylenes effectively underwent the ruthenium-catalyzed oxidative
      cyclization. A substrate possessing benzoic acid as well as a phenylphosphonic
      monoester moiety was smoothly cyclized with hex-3-yne to afford a compound having
      both isocoumarin and phosphaisocoumarin moieties. Alkenylphosphonic monoester
      afforded phosphorus 2-pyrone through oxidative cyclization with alkyne.
      Competition experiments between diaryl- and dialkylalkynes and between
      diarylacetylenes having p-methoxy and p-chloro groups gave results which showed
      that the present oxidative cyclizations were not affected by the electronic
      effects of alkynes. Mechanistic studies revealed C-H bond metalation to be the
      rate-limiting step. 

PMID- 24028217
TI  - Antisense suppression of cucumber (Cucumis sativus L.) sucrose synthase 3
      (CsSUS3) reduces hypoxic stress tolerance.
AB  - Sucrose synthase (SUS; EC 2.4.1.13) plays important roles in sugar metabolism and
      abiotic stress response. But the genes encoding SUS in cucumber (Cucumis sativus
      L.) have not been well studied. Here, we isolated four cucumber sucrose synthase
      genes (CsSUS). Among them, CsSUS3, which highly expressed in the roots, was
      chosen for further study. Immunolocalization and subcellular localization
      analysis indicated that CsSUS3 localized in the cytosol and the plasma membrane,
      and mainly existed in the companion cells of phloem in the roots. When suffering
      hypoxia stress from flooding, CsSUS3 expression and SUS activity in roots
      increased, especially in the lateral roots; moreover, the soluble SUS activity
      increased clearly, but the membrane fraction hardly changed. Compared with the
      wild-type cucumbers, the transgenic lines with antisense expression of CsSUS3
      were more sensitive to flooding. After 6 d of flooding, the SUS activity, soluble
      sugar and uridine 5'-diphosphate glucose (UDPG) content and the ratio of ATP/ADP
      in the roots of transgenic plants were significantly lower than that in wild-type
      plants. Moreover, the transgenic lines grew more slowly with more yellow necrosis
      in the leaves. These findings suggested CsSUS3 participated in resisting hypoxic
      stress. Furthermore, the mechanism of CsSUS3 in resisting hypoxic stress was also
      discussed. 

PMID- 24028219
TI  - Amino acid residues crucial for specificity of toxin-antitoxin interactions in
      the homologous Axe-Txe and YefM-YoeB complexes.
AB  - Toxin-antitoxin complexes are ubiquitous in bacteria. The specificity of
      interactions between toxins and antitoxins from homologous but non-interacting
      systems was investigated. Based on molecular modeling, selected amino acid
      residues were changed to assess which positions were crucial in the specificity
      of toxin-antitoxin interaction in the related Axe-Txe and YefM-YoeB complexes. No
      cross-interactions between wild-type proteins were detected. However, a single
      amino acid substitution that converts a Txe-specific residue to a YoeB-specific
      residue reduced, but did not abolish, Txe interaction with the Axe antitoxin.
      Interestingly, this alteration (Txe-Asp83Tyr) promoted functional interactions
      between Txe and the YefM antitoxin. The interactions between Txe-Asp83Tyr and
      YefM were sufficiently strong to abolish Txe toxicity and to allow effective
      corepression by YefM-Txe-Asp83Tyr of the promoter from which yefM-yoeB is
      expressed. We conclude that Asp83 in Txe is crucial for the specificity of toxin
      antitoxin interactions in the Axe-Txe complex and that swapping this residue for
      the equivalent residue in YoeB relaxes the specificity of the toxin-antitoxin
      interaction.

PMID- 24028220
TI  - Compromise of endogenous neuropeptide W production abrogates the dipsogenic and
      pressor effects of angiotensin II in adult male rats.
AB  - Neuropeptide W (NPW), an endogenous ligand for the G-protein coupled receptor
      GPR7, is produced in neurones in the rat hypothalamus and brain stem known to be
      important in the control of food intake and the neuroendocrine response to
      stress. In previous studies, central administration of NPW during the light phase
      increased food and water intake and elevated prolactin and corticosterone levels
      in conscious, unrestrained male rats. In the present study, central
      administration of small-interfering RNA (siRNA) reduced NPW levels in the
      hypothalamus and resulted in a failure of angiotensin II to stimulate water
      drinking or increase mean arterial pressure. In addition, siRNA-treated animals
      failed to mount a significant prolactin response to immobilisation stress, at the
      same time as maintaining a normal corticosterone response. These results suggest
      that endogenous NPW may be a physiologically relevant, downstream mediator of the
      central actions of angiotensin II to stimulate thirst and increase arterial
      pressure. In addition, NPW-producing neurones appear to participate in the
      hypothalamic mechanisms controlling prolactin (but not corticosterone) secretion.

PMID- 24028221
TI  - Influence of school beverage environment on the association of beverage
      consumption with physical education participation among US adolescents.
AB  - OBJECTIVES: We examined the association of adolescents' beverage consumption with
      physical activity and studied how their school beverage environment influences
      the association. METHODS: We used nationally representative data from the 2007
      Early Childhood Longitudinal Study-Kindergarten Cohort (n = 8850). We examined
      nonlinear associations of eighth graders' self-report of beverage consumption
      (milk, 100% juices, soft drinks) with moderate to vigorous physical activity and
      physical education (PE) participation using piecewise linear regression models.
      RESULTS: We found a nonlinear association of participation in PE class with
      beverage consumption, especially in schools with vending machines and those
      selling soft drinks. For students participating in PE less than 3 days per week,
      beverage consumption was not significantly associated with participation in PE
      class frequency. For students participating in PE 3 to 5 days per week, 1 more
      day of participation in PE class was associated with 0.43 (SE = 0.14; P = .002)
      more times per week of soft drink consumption and 0.41 (SE = 0.17; P = .021)
      fewer glasses per week of milk consumption. CONCLUSIONS: The more soft drink and
      less milk consumption related to high participation in PE class might be
      prevented by improving the beverage environment in schools. Systematic
      environmental interventions are needed to prevent such potential unintended
      consequences of promoting physical activity.

PMID- 24028222
TI  - Reported racial discrimination, trust in physicians, and medication adherence
      among inner-city African Americans with hypertension.
AB  - OBJECTIVES: We sought to determine if reported racial discrimination was
      associated with medication nonadherence among African Americans with hypertension
      and if distrust of physicians was a contributing factor. METHODS: Data were
      obtained from the TRUST project conducted in Birmingham, Alabama, 2006 to 2008.
      All participants were African Americans diagnosed with hypertension and receiving
      care at an inner city, safety net setting. Three categories of increasing
      adherence were defined based on the Morisky Medication Adherence Scale. Trust in
      physicians was measured with the Hall General Trust Scale, and discrimination was
      measured with the Experiences of Discrimination Scale. Associations were
      quantified by ordinal logistic regression, adjusting for gender, age, education,
      and income. RESULTS: The analytic sample consisted of 227 African American men
      and 553 African American women, with a mean age of 53.7 +/- 9.9 years. Mean
      discrimination scores decreased monotonically across increasing category of
      medication adherence (4.1, 3.6, 2.9; P = .025), though the opposite was found for
      trust scores (36.5, 38.5, 40.8; P < .001). Trust mediated 39% (95% confidence
      interval = 17%, 100%) of the association between discrimination and medication
      adherence. CONCLUSIONS: Within our sample of inner city African Americans with
      hypertension, racial discrimination was associated with lower medication
      adherence, and this association was partially mediated by trust in physicians.
      Patient, physician and system approaches to increase "earned" trust may enhance
      existing interventions for promoting medication adherence.

PMID- 24028223
TI  - Bogart et al. respond.

PMID- 24028224
TI  - Greene et al. respond.

PMID- 24028226
TI  - Overcoming legal liability concerns for school-based physical activity promotion.
AB  - Schools have been identified as a priority environment for physical activity
      promotion as a component of efforts to help prevent childhood obesity. A variety
      of school-based environmental and programmatic strategies have been proven
      effective in promoting physical activity both on-site and in the surrounding
      community. However, many schools are deterred by fears of increased risk of legal
      liability for personal injuries. We examine 3 school-based strategies for
      promoting physical activity--Safe Routes to School programs, joint use
      agreements, and playground enhancement--from a tort liability perspective, and
      describe how schools can substantially minimize any associated liability risk
      through injury prevention and other strategies. We also recommend approaches to
      help schools overcome their liability concerns and adopt these critically needed
      healthy school policies.

PMID- 24028227
TI  - The irony of prisoner health care.

PMID- 24028225
TI  - Networks to strengthen health systems for chronic disease prevention.
AB  - Interorganizational networks that harness the priorities, capacities, and skills
      of various agencies and individuals have emerged as useful approaches for
      strengthening preventive services in public health systems. We use examples from
      the Canadian Heart Health Initiative and Alberta's Primary Care Networks to
      illustrate characteristics of networks, describe the limitations of existing
      frameworks for assessing the performance of prevention-oriented networks, and
      propose a research agenda for guiding future efforts to improve the performance
      of these initiatives. Prevention-specific assessment strategies that capture
      relevant aspects of network performance need to be identified, and feedback
      mechanisms are needed that make better use of these data to drive change in
      network activities. 

PMID- 24028228
TI  - Understanding price elasticities to inform public health research and
      intervention studies: key issues.
AB  - Pricing policies such as taxes and subsidies are important tools in preventing
      and controlling a range of threats to public health. This is particularly so in
      tobacco and alcohol control efforts and efforts to change dietary patterns and
      physical activity levels as a means of addressing increases in noncommunicable
      diseases. To understand the potential impact of pricing policies, it is critical
      to understand the nature of price elasticities for consumer products. For
      example, price elasticities are key parameters in models of any food tax or
      subsidy that aims to quantify health impacts and cost-effectiveness. We detail
      relevant terms and discuss key issues surrounding price elasticities to inform
      public health research and intervention studies. 

PMID- 24028229
TI  - Families matter! Presexual risk prevention intervention.
AB  - Parent-based HIV prevention programming may play an important role in reaching
      youths early to help establish lifelong patterns of safe and healthy sexual
      behaviors. Families Matter! is a 5-session, evidence-based behavioral
      intervention designed for primary caregivers of children aged 9 to 12 years to
      promote positive parenting and effective parent-child communication about
      sexuality and sexual risk reduction. The program's 5-step capacity-building model
      was implemented with local government, community, and faith-based partners in 8
      sub-Saharan African countries with good intervention fidelity and high levels of
      participant retention. Families Matter! may be useful in other resource
      constrained settings. 

PMID- 24028230
TI  - OxyContin use on a rural midwest American Indian reservation: demographic
      correlates and reasons for using.
AB  - In 2009 we surveyed 400 tribal members of a midwestern American Indian
      reservation to assess the prevalence of OxyContin use. Thirty percent of tribal
      participants reported nonmedical use of OxyContin ever, 18.9% in the past year,
      and 13.4% in the past month. Participants aged 18 to 25 years were most likely to
      have used OxyContin. Reasons given for use of the drug included pain relief
      (59.3%) and getting high (52.2%), indicating a need for opioid treatment
      programs. 

PMID- 24028231
TI  - Woods and Gordon respond.

PMID- 24028232
TI  - The epidemic of chronic kidney disease of unknown etiology in Mesoamerica: a call
      for interdisciplinary research and action.

PMID- 24028233
TI  - The modifying influence of country development on the effect of individual
      educational attainment on self-rated health.
AB  - OBJECTIVES: We investigated how much the Human Development Index (HDI), a global
      measure of development, modifies the effect of education on self-reported health.
      METHODS: We analyzed cross-sectional World Health Survey data on 217,642
      individuals from 49 countries, collected in 2002 to 2005, with random-intercept
      multilevel linear regression models. RESULTS: We observed greater positive
      associations between educational levels and self-reported good health with
      increasing HDI. The magnitude of this effect modification of the education-health
      relation tended to increase with educational attainment. For example, before
      adjustment for effect modification, at comparable HDI, on average, finishing
      primary school was associated with better general health (b = 1.49; 95%
      confidence interval [CI] = 1.18, 1.80). With adjustment for effect modification
      by HDI, the impact became 4.63 (95% CI = 3.63, 5.62) for every 0.1 increase in
      HDI. Among those who completed high school, these associations were,
      respectively, 5.59 (95% CI = 5.20, 5.98) and 9.95 (95% CI = 8.89, 11.00).
      CONCLUSIONS: The health benefits of educational attainment are greater in
      countries with greater human development. Health inequalities attributable to
      education are, therefore, larger in more developed countries.

PMID- 24028234
TI  - Effects of a tobacco control intervention for teachers in India: results of the
      Bihar school teachers study.
AB  - OBJECTIVES: We assessed a school-based intervention designed to promote tobacco
      control among teachers in the Indian state of Bihar. METHODS: We used a cluster
      randomized design to test the intervention, which comprised educational efforts,
      tobacco control policies, and cessation support and was tailored to the local
      social context. In 2009 to 2011, we randomly selected 72 schools from
      participating school districts and randomly assigned them in blocks (rural or
      urban) to intervention or delayed-intervention control conditions. RESULTS:
      Immediately after the intervention, the 30-day quit rate was 50% in the
      intervention and 15% in the control group (P = .001). At the 9-month
      postintervention survey, the adjusted 6-month quit rate was 19% in the
      intervention and 7% in the control group (P = .06). Among teachers employed for
      the entire academic year of the intervention, the adjusted 6-month abstinence
      rates were 20% and 5%, respectively, for the intervention and control groups (P =
      .04). CONCLUSIONS: These findings demonstrate the potent impact of an
      intervention that took advantage of social resources among teachers, who can
      serve as role models for tobacco control in their communities.

PMID- 24028235
TI  - US trends in quality-adjusted life expectancy from 1987 to 2008: combining
      national surveys to more broadly track the health of the nation.
AB  - OBJECTIVES: We used data from multiple national health surveys to systematically
      track the health of the US adult population. METHODS: We estimated trends in
      quality-adjusted life expectancy (QALE) from 1987 to 2008 by using national
      mortality data combined with data on symptoms and impairments from the National
      Medical Expenditure Survey (1987), National Health Interview Survey (1987, 1994
      1995, 1996), Medical Expenditure Panel Survey (1992, 1996, 2000-2008), National
      Nursing Home Survey (1985, 1995, and 1999), and Medicare Current Beneficiary
      Survey (1992, 1994-2008). We decomposed QALE into changes in life expectancy,
      impairments, symptoms, and smoking and body mass index. RESULTS: Years of QALE
      increased overall and for all demographic groups-men, women, Whites, and Blacks
      despite being slowed by increases in obesity and a rising prevalence of some
      symptoms and impairments. Overall QALE gains were large: 2.4 years at age 25
      years and 1.7 years at age 65 years. CONCLUSIONS: Understanding and consistently
      tracking the drivers of QALE change is central to informed policymaking.
      Harmonizing data from multiple national surveys is an important step in building
      this infrastructure.

PMID- 24028236
TI  - Impaired-driving prevalence among US high school students: associations with
      substance use and risky driving behaviors.
AB  - OBJECTIVES: We examined the prevalence of impaired driving among US high school
      students and associations with substance use and risky driving behavior. METHODS:
      We assessed driving while alcohol or drug impaired (DWI) and riding with alcohol-
      or drug-impaired drivers (RWI) in a nationally representative sample of 11th
      grade US high school students (n = 2431). We examined associations with drinking
      and binge drinking, illicit drug use, risky driving, and demographic factors
      using multivariate sequential logistic regression analysis. RESULTS: Thirteen
      percent of 11th-grade students reported DWI at least 1 of the past 30 days, and
      24% reported RWI at least once in the past year. Risky driving was positively
      associated with DWI (odds ratio [OR] = 1.25; P < .001) and RWI (OR = 1.09; P <
      .05), controlling for binge drinking (DWI: OR = 3.17; P < .01; RWI: OR = 6.12; P
      < .001) and illicit drug use (DWI: OR = 5.91; P < .001; RWI: OR = 2.29; P = .05).
      DWI was higher for adolescents who drove after midnight (OR = 15.7), drove while
      sleepy or drowsy (OR = 8.6), read text messages (OR = 11.8), sent text messages
      (OR = 5.0), and made cell phone calls (OR = 3.2) while driving. CONCLUSIONS: Our
      findings suggest the need for comprehensive approaches to the prevention of DWI,
      RWI, and other risky driving behavior.

PMID- 24028237
TI  - Framing the consequences of childhood obesity to increase public support for
      obesity prevention policy.
AB  - OBJECTIVES: We examined the effects of messages describing consequences of
      childhood obesity on public attitudes about obesity prevention policy. METHODS:
      We collected data from 2 nationally representative Internet-based surveys. First,
      respondents (n = 444) evaluated the strength of 11 messages about obesity's
      consequences as reasons for government action. Second, we randomly assigned
      respondents (n = 2494) to a control group or to treatment groups shown messages
      about obesity consequences. We compared groups' attitudes toward obesity
      prevention, stratified by political ideology. RESULTS: Respondents perceived a
      message about the health consequences of childhood obesity as the strongest
      rationale for government action; messages about military readiness, bullying, and
      health care costs were rated particularly strong by conservatives, moderates, and
      liberals, respectively. A message identifying the consequences of obesity on
      military readiness increased conservatives' perceptions of seriousness,
      endorsement of responsibility beyond the individual, and policy support, compared
      with a control condition. CONCLUSIONS: The public considers several consequences
      of childhood obesity as strong justification for obesity prevention policy.
      Activating new or unexpected values in framing a health message could raise the
      health issue's salience for particular subgroups of the public.

PMID- 24028238
TI  - Creating a transdisciplinary research center to reduce cardiovascular health
      disparities in Baltimore, Maryland: lessons learned.
AB  - Cardiovascular disease (CVD) disparities continue to have a negative impact on
      African Americans in the United States, largely because of uncontrolled
      hypertension. Despite the availability of evidence-based interventions, their use
      has not been translated into clinical and public health practice. The Johns
      Hopkins Center to Eliminate Cardiovascular Health Disparities is a new
      transdisciplinary research program with a stated goal to lower the impact of CVD
      disparities on vulnerable populations in Baltimore, Maryland. By targeting
      multiple levels of influence on the core problem of disparities in Baltimore, the
      center leverages academic, community, and national partnerships and a novel
      structure to support 3 research studies and to train the next generation of CVD
      researchers. We also share the early lessons learned in the center's design. 

PMID- 24028240
TI  - Fish oils, misconceptions and the environment.

PMID- 24028239
TI  - Trends in racial and ethnic disparities in infant mortality rates in the United
      States, 1989-2006.
AB  - OBJECTIVES: We sought to measure overall disparities in pregnancy outcome,
      incorporating data from the many race and ethnic groups that compose the US
      population, to improve understanding of how disparities may have changed over
      time. METHODS: We used Birth Cohort Linked Birth-Infant Death Data Files from US
      Vital Statistics from 1989-1990 and 2005-2006 to examine multigroup indices of
      racial and ethnic disparities in the overall infant mortality rate (IMR), preterm
      birth rate, and gestational age-specific IMRs. We calculated selected absolute
      and relative multigroup disparity metrics weighting subgroups equally and by
      population size. RESULTS: Overall IMR decreased on the absolute scale, but
      increased on the population-weighted relative scale. Disparities in the preterm
      birth rate decreased on both the absolute and relative scales, and across equally
      weighted and population-weighted indices. Disparities in preterm IMR increased on
      both the absolute and relative scales. CONCLUSIONS: Infant mortality is a common
      bellwether of general and maternal and child health. Despite significant
      decreases in disparities in the preterm birth rate, relative disparities in
      overall and preterm IMRs increased significantly over the past 20 years.

PMID- 24028241
TI  - Excess infant mortality among Native Hawaiians: identifying determinants for
      preventive action.
AB  - OBJECTIVES: We identified potential determinants and cause-specific sources of
      excess infant mortality among Native Hawaiians. METHODS: We compared infant
      mortality rates among Native Hawaiians and Whites by using data from the 2002 to
      2009 Hawai'i State Linked Birth/Infant Death Cohort File. We evaluated the
      components of excess infant mortality by age and underlying cause of death as
      well as maternal sociodemographic, behavioral, and chronic condition disparities.
      RESULTS: The Native Hawaiian infant mortality rate was more than twice that for
      Whites (7.9 vs 3.5/1000 live births). Excess Native Hawaiian infant mortality was
      equally apportioned to neonatal and postneonatal deaths. Preterm-related causes
      of death accounted for 43.9% of the infant mortality disparity, followed by
      sudden unexpected infant death (21.6%) and injury (5.6%). In multivariable
      models, maternal educational inequality accounted for the largest portion of the
      neonatal mortality disparity (20.9%); younger maternal age (12.2%) and smoking
      (9.5%) were the only significant contributors to the postneonatal mortality
      disparity. CONCLUSIONS: Addressing educational inequalities, promoting safe sleep
      practices, and reducing smoking among Native Hawaiian mothers would help to
      eliminate excess infant mortality.

PMID- 24028242
TI  - Perceived discrimination and racial/ethnic disparities in youth problem
      behaviors.

PMID- 24028243
TI  - Attitudes toward mental illness in adults by mental illness-related factors and
      chronic disease status: 2007 and 2009 Behavioral Risk Factor Surveillance System.
AB  - OBJECTIVES: We examined how attitudes toward mental illness treatment and its
      course differ by serious psychological distress, mental illness treatment,
      chronic disease, and sociodemographic factors using representative state-based
      data. METHODS: Using data from jurisdictions supporting the Behavioral Risk
      Factor Surveillance System's Mental Illness and Stigma Module (35 states, the
      District of Columbia, and Puerto Rico), we compared adjusted proportions of
      adults agreeing that "Treatment can help people with mental illness lead normal
      lives" (treatment effectiveness) and that "People are generally caring and
      sympathetic to people with mental illness" (supportive environment), by
      demographic characteristics, serious psychological distress, chronic disease
      status, and mental illness treatment. RESULTS: Attitudes regarding treatment
      effectiveness and a supportive environment for people with mental illness varied
      within and between groups. Most adults receiving mental illness treatment agreed
      that treatment is effective. Fewer adults with serious psychological distress
      than those without such distress agreed that treatment is effective. Fewer of
      those receiving treatment, those with psychological distress, and those with
      chronic disease perceived the environment as supportive. CONCLUSIONS: These data
      can be used to target interventions for population subgroups with less favorable
      attitudes and for surveillance.

PMID- 24028244
TI  - Environmental conditions in low-income urban housing: clustering and associations
      with self-reported health.
AB  - OBJECTIVES: We explored prevalence and clustering of key environmental conditions
      in low-income housing and associations with self-reported health. METHODS: The
      Health in Common Study, conducted between 2005 and 2009, recruited participants
      (n = 828) from 20 low-income housing developments in the Boston area. We
      interviewed 1 participant per household and conducted a brief inspection of the
      unit (apartment). We created binary indexes and a summed index for household
      exposures: mold, combustion by-products, secondhand smoke, chemicals, pests, and
      inadequate ventilation. We used multivariable logistic regression to examine the
      associations between each index and household characteristics and between each
      index and self-reported health. RESULTS: Environmental problems were common; more
      than half of homes had 3 or more exposure-related problems (median summed index =
      3). After adjustment for household-level demographics, we found clustering of
      problems in site (P < .01) for pests, combustion byproducts, mold, and
      ventilation. Higher summed index values were associated with higher adjusted odds
      of reporting fair-poor health (odds ratio = 2.7 for highest category; P < .008
      for trend). CONCLUSIONS: We found evidence that indoor environmental conditions
      in multifamily housing cluster by site and that cumulative exposures may be
      associated with poor health.

PMID- 24028245
TI  - Taxing junk food to counter obesity.
AB  - We examined the advantages and disadvantages of implementing a junk food tax as
      an intervention to counter increasing obesity in North America. Small excise
      taxes are likely to yield substantial revenue but are unlikely to affect obesity
      rates. High excise taxes are likely to have a direct impact on weight in at-risk
      populations but are less likely to be politically palatable or sustainable.
      Ultimately, the effectiveness of earmarked health programs and subsidies is
      likely to be a key determinant of tax success in the fight against obesity. 

PMID- 24028246
TI  - Linking research to global health equity: the contribution of product development
      partnerships to access to medicines and research capacity building.
AB  - Certain product development partnerships (PDPs) recognize that to promote the
      reduction of global health disparities they must create access to their products
      and strengthen research capacity in developing countries. We evaluated the
      contribution of 3 PDPs--Medicines for Malaria Venture, Drugs for Neglected
      Diseases Initiative, and Institute for One World Health--according to Frost and
      Reich's access framework. We also evaluated PDPs' capacity building in low- and
      middle-income countries at the individual, institutional, and system levels. We
      found that these PDPs advance public health by ensuring their products'
      registration, distribution, and adoption into national treatment policies in
      disease-endemic countries. Nonetheless, ensuring broad, equitable access for
      these populations--high distribution coverage; affordability, particularly for
      the poor; and adoption at provider and end-user levels--remains a challenge.

PMID- 24028247
TI  - Perceptions of relative risk of snus and cigarettes among US smokers.
AB  - In a survey of 1836 adult US smokers, when using a direct comparison measure,
      22.1% reported snus was less harmful than were cigarettes. When asked indirectly
      (estimating the health risk of snus and cigarettes in 2 separate questions and
      comparing the answers to each other), 51.6% rated snus as less risky. The Food
      and Drug Administration should consider both direct and indirect measures when
      perceived risk data are presented as evidence for tobacco regulation. 

PMID- 24028248
TI  - Effect of the Framework Convention on Tobacco Control and voluntary industry
      health warning labels on passage of mandated cigarette warning labels from 1965
      to 2012: transition probability and event history analyses.
AB  - OBJECTIVES: We quantified the pattern and passage rate of cigarette package
      health warning labels (HWLs), including the effect of the Framework Convention on
      Tobacco Control (FCTC) and HWLs voluntarily implemented by tobacco companies.
      METHODS: We used transition probability matrices to describe the pattern of HWL
      passage and change rate in 4 periods. We used event history analysis to estimate
      the effect of the FCTC on adoption and to compare that effect between countries
      with voluntary and mandatory HWLs. RESULTS: The number of HWLs passed during each
      period accelerated, from a transition rate among countries that changed from 2.42
      per year in 1965-1977 to 6.71 in 1977-1984, 8.42 in 1984-2003, and 22.33 in 2003
      2012. The FCTC significantly accelerated passage of FCTC-compliant HWLs for
      countries with initially mandatory policies with a hazard of 1.27 per year (95%
      confidence interval = 1.11, 1.45), but only marginally increased the hazard for
      countries that had an industry voluntary HWL of 1.68 per year (95% confidence
      interval = 0.95, 2.97). CONCLUSIONS: Passage of HWLs is accelerating, and the
      FCTC is associated with further acceleration. Industry voluntary HWLs slowed
      mandated HWLs.

PMID- 24028249
TI  - Reduction in male suicide mortality following the 2006 Russian alcohol policy: an
      interrupted time series analysis.
AB  - OBJECTIVES: We took advantage of a natural experiment to assess the impact on
      suicide mortality of a suite of Russian alcohol policies. METHODS: We obtained
      suicide counts from anonymous death records collected by the Russian Federal
      State Statistics Service. We used autoregressive integrated moving average
      (ARIMA) interrupted time series techniques to model the effect of the alcohol
      policy (implemented in January 2006) on monthly male and female suicide counts
      between January 2000 and December 2010. RESULTS: Monthly male and female suicide
      counts decreased during the period under study. Although the ARIMA analysis
      showed no impact of the policy on female suicide mortality, the results revealed
      an immediate and permanent reduction of about 9% in male suicides (Ln omega0 = 
      0.096; P = .01). CONCLUSIONS: Despite a recent decrease in mortality, rates of
      alcohol consumption and suicide in Russia remain among the highest in the world.
      Our analysis revealed that the 2006 alcohol policy in Russia led to a 9%
      reduction in male suicide mortality, meaning the policy was responsible for
      saving 4000 male lives annually that would otherwise have been lost to suicide.
      Together with recent similar findings elsewhere, our results suggest an important
      role for public health and other population level interventions, including
      alcohol policy, in reducing alcohol-related harm.

PMID- 24028250
TI  - Traditional Christian values and women's reproductive rights in modern Russia--is
      a consensus ever possible?
AB  - Recently in Russia, abortion rights have been attacked. For decades, Russian
      women could have an elective abortion up to week 12 of pregnancy; between 12 and
      22 weeks, medical or social grounds were required for an abortion. In mid 2011, a
      group of Parliamentarians teamed up with Russian Orthodox Church activists and
      announced their desire to ban abortions, and the new version of the health law
      with restricting amendments was introduced: a mandatory waiting period,
      physicians' conscientious objection, and limiting the social indications for late
      term abortion. Evidence indicates that restricting legislative changes based on
      "traditional" values could significantly limit women's reproductive choices
      (e.g., access to abortion), a setback to women's rights to exert control over
      their bodies and their lives. 

PMID- 24028251
TI  - Minimal clinically important difference (MCID)--adding meaning to statistical
      inference.

PMID- 24028252
TI  - The relationship between gun ownership and firearm homicide rates in the United
      States, 1981-2010.
AB  - OBJECTIVES: We examined the relationship between levels of household firearm
      ownership, as measured directly and by a proxy-the percentage of suicides
      committed with a firearm-and age-adjusted firearm homicide rates at the state
      level. METHODS: We conducted a negative binomial regression analysis of panel
      data from the Centers for Disease Control and Prevention's Web-Based Injury
      Statistics Query and Reporting Systems database on gun ownership and firearm
      homicide rates across all 50 states during 1981 to 2010. We determined fixed
      effects for year, accounted for clustering within states with generalized
      estimating equations, and controlled for potential state-level confounders.
      RESULTS: Gun ownership was a significant predictor of firearm homicide rates
      (incidence rate ratio = 1.009; 95% confidence interval = 1.004, 1.014). This
      model indicated that for each percentage point increase in gun ownership, the
      firearm homicide rate increased by 0.9%. CONCLUSIONS: We observed a robust
      correlation between higher levels of gun ownership and higher firearm homicide
      rates. Although we could not determine causation, we found that states with
      higher rates of gun ownership had disproportionately large numbers of deaths from
      firearm-related homicides.

PMID- 24028253
TI  - Promoting civic engagement post-release from correctional facilities.

PMID- 24028254
TI  - Purtle responds.

PMID- 24028255
TI  - Work-related injury surveillance in Vietnam: a national reporting system model.
AB  - Developing nations bear a substantial portion of the global burden of injury.
      Public health surveillance models in developing countries should recognize injury
      risks for all levels of society and all causes and should incorporate various
      groups of workers and industries, including subsistence agriculture. However,
      many developing nations do not have an injury registration system; current data
      collection methods result in gross national undercounts of injuries, failing to
      distinguish injuries that occur during work. In 2006, we established an active
      surveillance system in Vietnam's Xuan Tien commune and investigated potential
      methods for surveillance of work-related injuries. On the basis of our findings,
      we recommend a national model for work-related injury surveillance in Vietnam
      that builds on the existing health surveillance system. 

PMID- 24028256
TI  - Modern cholera in the Americas: an opportunistic societal infection.
AB  - In the Americas, the only two cholera epidemics of the past century have occurred
      in the past 25 years. Lessons from the 1991 Peruvian cholera epidemic can help to
      focus and refine the response to the current Haitian epidemic. After three years
      of acute epidemic response, we have an opportunity to refocus on the chronic
      conditions that make societies vulnerable to cholera. More importantly, even as
      international attention wanes in the aftermath of the earthquake and acute
      epidemic, we are faced with a need for continued and coordinated investment in
      improving Haiti's structural defenses against cholera, in particular access to
      improved water and sanitation. 

PMID- 24028257
TI  - The combined effects of the expansion of primary health care and conditional cash
      transfers on infant mortality in Brazil, 1998-2010.
AB  - OBJECTIVES: I examined the combined effects of access to primary care through the
      Family Health Program (FHP) and conditional cash transfers from the Bolsa Familia
      Program (BFP) on postneonatal infant mortality (PNIM) in Brazil. METHODS: I
      employed longitudinal ecological analysis using panel data from 4583 Brazilian
      municipalities from 1998 to 2010, totaling 54,253 observations. I estimated fixed
      effects ordinary least squares regressions models with PNIM rate as the dependent
      variable and FHP, BFP, and their interactions as the main independent variables
      of interest. RESULTS: The association of higher FHP coverage with lower PNIM
      became stronger as BFP coverage increased. At the means of all other variables,
      when BFP coverage was 25%, predicted PNIM was 5.24 (95% confidence interval [CI]
      = 4.95, 5.53) for FHP coverage = 0% and 3.54 (95% CI = 2.77, 4.31) for FHP
      coverage = 100%. When BFP coverage was 60%, predicted PNIM was 4.65 (95% CI =
      4.36, 4.94) when FHP coverage = 0% and 1.38 (95% CI = 0.88, 1.89) when FHP
      coverage = 100%. CONCLUSIONS: The effect of the FHP depends on the expansion of
      the BFP. For impoverished, underserved populations, combining supply- and demand
      side interventions may be necessary to improve health outcomes.

PMID- 24028258
TI  - Thinking locally, acting globally?

PMID- 24028260
TI  - Social isolation: a predictor of mortality comparable to traditional clinical
      risk factors.
AB  - OBJECTIVES: We explored the relationship between social isolation and mortality
      in a nationally representative US sample and compared the predictive power of
      social isolation with that of traditional clinical risk factors. METHODS: We used
      data on 16,849 adults from the Third National Health and Nutrition Examination
      Survey and the National Death Index. Predictor variables were 4 social isolation
      factors and a composite index. Comparison predictors included smoking, obesity,
      elevated blood pressure, and high cholesterol. Unadjusted Kaplan-Meier tables and
      Cox proportional hazards regression models controlling for sociodemographic
      characteristics were used to predict mortality. RESULTS: Socially isolated men
      and women had worse unadjusted survival curves than less socially isolated
      individuals. Cox models revealed that social isolation predicted mortality for
      both genders, as did smoking and high blood pressure. Among men, individual
      social predictors included being unmarried, participating infrequently in
      religious activities, and lacking club or organization affiliations; among women,
      significant predictors were being unmarried, infrequent social contact, and
      participating infrequently in religious activities. CONCLUSIONS: The strength of
      social isolation as a predictor of mortality is similar to that of well
      documented clinical risk factors. Our results suggest the importance of assessing
      patients' level of social isolation.

PMID- 24028259
TI  - Secondhand smoke exposure and smoking behavior among young adult bar patrons.
AB  - OBJECTIVES: We described frequency of secondhand smoke (SHS) exposure among young
      adults patronizing bars and associations between SHS exposure, attitudes, and
      smoking behavior. METHODS: We collected cross-sectional surveys from randomized
      time-location samples of bar patrons aged 18 to 26 years in San Diego,
      California, and Oklahoma City and Tulsa, Oklahoma, in 2010 to 2011. Multivariate
      logistic regression evaluated associations between SHS exposure, attitudes about
      dangers of SHS, susceptibility to smoking initiation among nonsmokers, and quit
      attempts among current smokers. RESULTS: More than 80% of respondents reported
      past 7-day exposure to any SHS, and more than 70% reported exposure at a bar.
      Current smokers reported more SHS exposure in cars and their own homes than did
      nonsmokers. Among nonsmokers, SHS exposure was associated with susceptibility to
      initiation, but those who believed that SHS exposure is harmful were less
      susceptible. Belief that SHS is dangerous was associated with quit attempts among
      smokers. CONCLUSIONS: Smoke-free environments and education about the harms of
      SHS may decrease tobacco use among young adults who frequent bars, where they are
      heavily exposed to SHS.

PMID- 24028261
TI  - Impact of the 2004 tsunami on self-reported physical health in Thailand for the
      subsequent 2 years.
AB  - OBJECTIVES: We examined self-reported physical health during the first 2 years
      following the 2004 tsunami in Thailand. METHODS: We assessed physical health with
      the revised Short Form Health Survey. We evaluated 6 types of tsunami exposure:
      personal injury, personal loss of home, personal loss of business, loss of family
      member, family member's injury, and family's loss of business. We examined the
      relationship between tsunami exposure and physical health with multivariate
      linear regression. RESULTS: One year post-tsunami, we interviewed 1931
      participants (97.2% response rate), and followed up with 1855 participants 2
      years after the tsunami (96.1% follow-up rate). Participants with personal injury
      or loss of business reported poorer physical health than those unaffected (P <
      .001), and greater health impacts were found for women and older individuals.
      CONCLUSIONS: Exposure to the tsunami disaster adversely affected physical health,
      and its impact may last for longer than 1 year, which is the typical time when
      most public and private relief programs withdraw.

PMID- 24028263
TI  - Local tobacco control: application of the essential public health services model
      in a county health department's efforts to Put It Out Rockland.
AB  - In 2000, Rockland County, a small suburban county north of New York City,
      dedicated $1 million of its Master Settlement Agreement funds to a comprehensive
      tobacco control program, Put It Out Rockland. Developed and implemented by the
      county health department, this program used an essential public health services
      model and an ongoing financial investment, within the context of strong statewide
      tobacco control efforts, to lower adult smoking rates to 9.7% and to reduce both
      smoking among youths and exposure to secondhand smoke over the ensuing decade. By
      combining state funds and local dollars for a total of $6.75 cost per capita,
      this comprehensive effort yielded 11 000 fewer smokers and translated to a
      potential savings of more than $24 million for the county. 

PMID- 24028262
TI  - Medicaid expansion initiative in Massachusetts: enrollment among substance
      abusing homeless adults.
AB  - OBJECTIVES: We assessed whether homeless adults entering substance abuse
      treatment in Massachusetts were less likely than others to enroll in Medicaid
      after implementation of the MassHealth Medicaid expansion program in 1997.
      METHODS: We used interrupted time-series analysis in data on substance abuse
      treatment admissions from the Treatment 0Episode Data Set (1992-2009) to evaluate
      Medicaid coverage rates in Massachusetts and to identify whether trends differed
      between homeless and housed participants. We also compared Massachusetts data
      with data from 17 other states and the District of Columbia combined. RESULTS:
      The percentage of both homeless and housed people entering treatment with
      Medicaid increased approximately 21% after expansion (P = .01), with an average
      increase of 5.4% per year over 12 years (P = .01). The increase in coverage was
      specific to Massachusetts, providing evidence that the MassHealth policy was the
      cause of this increase. CONCLUSIONS: Findings provide evidence in favor of state
      participation in the Medicaid expansion in January 2014 under the Affordable Care
      Act and suggest that hard-to-reach vulnerable groups such as substance-abusing
      homeless adults are as likely as other population groups to benefit from this
      policy.

PMID- 24028264
TI  - Environmental public health and recommendations for fish oil and seafood intake.

PMID- 24028265
TI  - Critical opportunities for public health law: a call for action.
AB  - Although legal interventions are responsible for many sentinel public health
      achievements, law is underutilized as a tool for advancing population health. Our
      purpose was to identify critical opportunities for public health lawmaking. We
      articulated key criteria and illustrated their use with 5 examples. These
      opportunities involve significant health problems that are potentially amenable
      to change through law and for which an effective legal intervention is available:
      optimizing graduated driver licensing laws, increasing tax rates on alcoholic
      beverages, regulating sodium in foods, enacting laws to facilitate reversal of
      opioid overdoses, and improving mental health interventions in the college
      setting. We call for a national conversation about critical opportunities for
      public health law to advance evidence-based policymaking. 

PMID- 24028266
TI  - Driving after drug or alcohol use by US high school seniors, 2001-2011.
AB  - OBJECTIVES: We examined prevalence, trends, and correlates of driving or riding
      after use of drugs or alcohol among US high school seniors from 2001 to 2011.
      METHODS: Data come from Monitoring the Future, an annual survey of nationally
      representative samples of high school seniors. We used logistic regressions with
      data from more than 22,000 respondents to examine multivariate associations with
      demographic and lifestyle factors. RESULTS: Large numbers of US high school
      seniors put themselves and others at great risk of harm by driving after using
      marijuana or other illicit drugs or drinking alcohol or by riding in a vehicle
      whose driver had used marijuana, other illicit drugs, or alcohol. Driving after
      drinking has declined in recent years, but driving after use of marijuana has
      increased. A higher percentage of students reported driving after using marijuana
      than after having 5 or more alcoholic drinks. Risky driving and riding behaviors
      differed little between demographic subgroups but considerably according to
      lifestyle factors. CONCLUSIONS: Stronger efforts are needed to combat adolescent
      driving under the influence of illicit drugs.

PMID- 24028267
TI  - Prevalence of HCV infection among clients in community-based health settings in
      Hawaii, 2002-2010: assessing risk factors.
AB  - OBJECTIVES: We sought to determine the prevalence of HCV infection and identify
      risk factors associated with HCV infection among at-risk clients presenting to
      community-based health settings in Hawaii. METHODS: Clients from 23 community
      based sites were administered risk factor questionnaires and screened for HCV
      antibodies from December 2002 through May 2010. We performed univariate and
      multivariate logistic regression analyses. RESULTS: Of 3306 participants included
      in the analysis, 390 (11.8%) tested antibody positive for HCV. Highest HCV
      antibody prevalence (17.0%) was in persons 45 to 64 years old compared with all
      other age groups. Significant independent risk factors were current or prior
      injection drug use (P < .001), blood transfusion prior to July 1992 (P = .002),
      and having an HCV-infected sex partner (P = .03). Stratification by gender
      revealed sexual exposure to be significant for males (P = .001). CONCLUSIONS:
      Despite Hawaii's ethnic diversity, high hepatocellular carcinoma incidence, and a
      statewide syringe exchange program in place since the early 1990s, our HCV
      prevalence and risk factor findings are remarkably consistent with those reported
      from the mainland United States. Hence, effective interventions identified from
      US mainland population studies should be generalizable to Hawaii.

PMID- 24028268
TI  - Exploring risk factors in Latino cardiovascular disease: the role of education,
      nativity, and gender.
AB  - OBJECTIVES: We examined 3 cardiovascular disease risk factors by nativity and
      gender, evaluating evidence for education and health behaviors in explaining the
      "Hispanic Health Paradox." METHODS: We analyzed 2001-2008 National Health and
      Nutrition Examination Survey data for adults (n = 6032) to compare hypertension,
      high waist circumference, and diabetes for US- and foreign-born Mexican men and
      women. We controlled for age, depression, and health insurance. RESULTS:
      Cardiovascular disease risk factors differed by education, nativity, and gender.
      Higher education was associated with higher odds of hypertension and high waist
      circumference for men and women regardless of nativity. As education increased,
      the odds of diabetes increased for US-born women, showing a gradient for this
      population. Finally, foreign-born Mexican women with 5 to 19 years in the United
      States conferred the highest odds of having diabetes, whereas foreign-born men
      with less than 5 years in the United States had the lowest odds for high waist
      circumference and presence of diabetes. CONCLUSIONS: Results contest assumptions
      of the Hispanic Health Paradox and suggest new approaches. New research can yield
      accurate information to ensure the development of appropriate interventions,
      decreasing health disparities endemic to a subgroup of Latinos.

PMID- 24028269
TI  - Phenylboronic acid-installed polymeric micelles for targeting sialylated epitopes
      in solid tumors.
AB  - Ligand-mediated targeting of nanocarriers to tumors is an attractive strategy for
      increasing the efficiency of chemotherapies. Sialylated glycans represent a
      propitious target as they are broadly overexpressed in tumor cells. Because
      phenylboronic acid (PBA) can selectively recognize sialic acid (SA), herein, we
      developed PBA-installed micellar nanocarriers incorporating the parent complex of
      the anticancer drug oxaliplatin, for targeting sialylated epitopes overexpressed
      on cancer cells. Following PBA-installation, the micelles showed high affinity
      for SA, as confirmed by fluorescence spectroscopy even at intratumoral pH
      conditions, i.e., pH 6.5, improving their cellular recognition and uptake and
      enhancing their in vitro cytotoxicity against B16F10 murine melanoma cells. In
      vivo, PBA-installed micelles effectively reduced the growth rate of both
      orthotopic and lung metastasis models of melanoma, suggesting the potential of
      PBA-installed nanocarriers for enhanced tumor targeting. 

PMID- 24028270
TI  - A comparison of laparoscopic radiofrequency ablation versus systemic therapy
      alone in the treatment of breast cancer metastasis to the liver.
AB  - OBJECTIVES: There is controversy about the roles of locoregional therapies in
      patients with liver metastases from breast cancer (LMBC). The aim of this study
      was to analyse survival after laparoscopic radiofrequency ablation (RFA) of LMBC
      and to compare this with survival in patients receiving systemic therapy (ST)
      alone. METHODS: During 1996-2011, 24 patients who had failed to respond or had
      shown an incomplete response to ST underwent laparoscopic RFA for LMBC. Outcomes
      in these patients were compared with those in 32 patients with LMBC matched by
      tumour size and number, but treated with ST alone. Clinical parameters and
      overall survival were compared using t-tests, chi-squared tests and Kaplan-Meier
      analysis. RESULTS: The groups were similar in hormone receptor status and
      chemotherapy exposure. In the laparoscopic RFA and ST groups, respectively, the
      mean +/- standard deviation size of the dominant liver tumour and the number of
      tumours per patient were 3.7 +/- 0.4 cm and 2.4 +/- 0.4 cm, and 2.6 +/- 0.4
      tumours and 3.3 +/- 0.4 tumours, respectively. These differences were not
      significant. At a median follow-up of 20 months in the laparoscopic RFA group,
      42% of patients were found to have developed local liver recurrence, 63% had
      developed new liver disease and 38% had developed extrahepatic disease. Overall
      survival after the diagnosis of liver metastasis was 47 months in the
      laparoscopic RFA group and 9 months in the ST-only group (P = 0.0001). Five-year
      survival after the diagnosis of liver metastasis was 29% in the RFA group and 0%
      in the ST-only group. CONCLUSIONS: This is the first study to compare outcomes in
      RFA and ST, respectively, in LMBC. The results show that survival after
      laparoscopic RFA plus ST is better than that after ST alone.

PMID- 24028272
TI  - Progress in the technology of neuromodulation: the emperor's new clothes?

PMID- 24028271
TI  - Failure to follow evidence-based best practice guidelines in the treatment of
      severe acute pancreatitis.
AB  - OBJECTIVES: Evidence-based guidelines for the treatment of severe acute
      pancreatitis have been established. This study was conducted to investigate the
      hypothesis that deviation from guidelines occurs frequently. METHODS: With
      institutional review board approval, the outside medical records of patients with
      severe pancreatitis who were transferred to the study institution during the
      period from July 2005 to May 2012 were reviewed. Severe pancreatitis was defined
      using the Atlanta Classification criteria. Records were reviewed with respect to
      published guidelines defining the appropriate use of imaging, antibiotics and
      nutritional support. RESULTS: A total of 538 patients with acute pancreatitis
      were identified. Of 67 patients with severe acute pancreatitis, 44 (66%) were
      male. The mean age of the patients was 55 years. Forty-five of 61 (74%) patients
      for whom relevant data were available were imaged upon admission, but only 15
      (31%) patients were imaged appropriately by computerized tomography with i.v.
      contrast to assess the presence of necrosis or other complications. In patients
      for whom relevant data were available, prophylactic antibiotics were initiated in
      the absence of culture data or a specific infectious target in 26 (53%) patients.
      Total parenteral nutrition (TPN) was administered to 38 (60%) of 63 patients for
      whom relevant data were available; only 10 (17%) patients received enteric
      feeding. No nutritional support was provided to 15 (23%) patients. CONCLUSIONS:
      Adherence to best practice guidelines in the treatment of severe pancreatitis is
      poor. The consistent application of current knowledge might improve outcomes in
      these patients.

PMID- 24028273
TI  - Neurotech report.

PMID- 24028274
TI  - Effects of responsive electrical brain stimulation on intracranial
      electroencephalogram spikes.
AB  - OBJECTIVES: Responsive cortical electrical stimulation with implanted devices is
      under investigation for seizures. While designed to terminate seizures, might
      this stimulation also affect the underlying epileptic process of seizure
      generation? MATERIALS AND METHODS: Four patients undergoing intracranial
      electroencephalogram (EEG) for seizure localization had an external responsive
      neurostimulator (eRNS) connected to their seizure-onset zones. The eRNS detected
      interictal EEG spikes and stimulated at the focus. We quantified spikes at three
      locations: (1) near stimulation, (2) remote but in the same lobe as stimulation,
      and (3) in different lobe from stimulation. Ten-minute windows were analyzed at
      three times: (1) baseline, (2) after the first four hours of stimulation, and (3)
      poststimulation. One blinded investigator performed manual spike counts.
      Quantitative measures were total spikes, spike-free intervals (continuous ten-sec
      segments with no spikes), and spike clusters (one-sec intervals with three or
      more spikes). RESULTS: Some changes in spikes occurred in each patient, but no
      uniform pattern emerged. Two general observations were made: (1) spike counts
      within a given patient exhibited internally consistent changes with stimulation;
      (2) across patients, the nature of spike count changes varied, indicating patient
      to-patient variability. For example, poststimulation, two patients had more and
      two patients had fewer total spikes. However, when spikes decreased near
      stimulation, they decreased at other sites, and when spikes increased near
      stimulation, they increased at other sites. CONCLUSIONS: Changes in spike
      occurrence, organization, and topography with stimulation suggest the eRNS
      affected spike generation and may affect the underlying interictal epileptic
      process. Case-to-case variability may be due to individual patient factors, and
      its significance is yet to be determined.

PMID- 24028275
TI  - FXTAS in an unmethylated mosaic male with fragile X syndrome from Chile.
AB  - Carriers of an FMR1 premutation allele (55-200 CGG repeats) often develop the
      neurodegenerative disorders, fragile X-associated tremor/ataxia syndrome (FXTAS).
      Neurological signs of FXTAS, parkinsonism and rapid onset of cognitive decline
      have not been reported in individuals with an unmethylated full mutation (FM).
      Here, we report a Chilean family affected with FXS, inherited from a parent
      carrier of an FMR1 unmethylated full mosaic allele, who presented with a fast
      progressing FXTAS. This case suggests that the definition of FXTAS may need to be
      broadened to not only include those with a premutation but also those with an
      expanded allele in FM range with a lack of methylation leading to elevated FMR1
      mRNA expression levels and subsequent RNA toxicity. 

PMID- 24028277
TI  - Pronuclear morphology evaluation for fresh in vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI) cycles: a systematic review.
AB  - The current systematic review was aimed to assess the effectiveness of the zygote
      morphology evaluation in fresh in vitro fertilization (IVF) and intracytoplasmic
      sperm injection (ICSI) cycles. All available studies reporting on zygote
      morphology and clinical and/or biological outcomes were analyzed. Forty studies
      were included in the final analysis. Fourteen different zygote scoring systems
      were employed. Zygote morphology correlated significantly with embryo quality and
      cleavage, blastocyst stage, embryonic chromosome status, in a high proportion of
      the studies which assessed the specific outcome [15/25 (60%), 15/20 (75%), 7/8
      (87.5%), 6/6 (100%), respectively]. On the other hand, only a reduced proportion
      of papers showed a statistically significant relationship between implantation,
      pregnancy and delivery/live-birth rates and zygote morphology score [12/23
      (52.2%), 12/25 (48%), 1/4 (25%), respectively]. In conclusion, our findings
      demonstrate the lack of conclusive data on the clinical efficacy of the zygote
      morphology evaluation in fresh IVF/ICSI cycles, even if biological results
      showing a good relationship with embryo viability suggest a role in cycles in
      which the transfer/freezing is performed at day 1. 

PMID- 24028276
TI  - Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in
      rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella
      vaccine formulations.
AB  - Shigellosis is a worldwide disease, characterized by abdominal pain, fever,
      vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and
      other primates are the only animals that are naturally susceptible to
      shigellosis. A suitable animal model is required for the pre-clinical evaluation
      of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1
      1617 strain required to produce dysentery in four of five (80% attack rate)
      monkeys using an escalating dose range for three groups [2 * 10(8) , 2 * 10(9)
      and 2 * 10(10) colony forming unit (CFU)] was determined. In addition, the
      monkeys were re-infected. The identified optimal challenge dose was 2 * 10(9)
      CFU; this dose elicited 60% protection in monkeys when they were re-challenged
      with a one log higher dose (2 * 10(10) CFU). The challenge dose, 2 * 10(10) CFU,
      produced severe dysentery in all monkeys, with one monkey dying within 24 h,
      elicited 100% protection when re-challenged with the same dose. All monkeys
      exhibited immune responses. This study concludes that the rhesus monkey model
      closely mimics the disease and immune response seen in humans and is a suitable
      animal model for the pre-clinical evaluation of Shigella vaccine candidates.
      Prior infection with the 1617 strain can protect monkeys against subsequent re
      challenges with homologous strains.

PMID- 24028278
TI  - The integral and extrinsic bioactive proteins in the aqueous extracted soybean
      oil bodies.
AB  - Soybean oil bodies (OBs), naturally pre-emulsified soybean oil, have been
      examined by many researchers owing to their great potential utilizations in food,
      cosmetics, pharmaceutical, and other applications requiring stable oil-in-water
      emulsions. This study was the first time to confirm that lectin, Gly m Bd 28K (Bd
      28K, one soybean allergenic protein), Kunitz trypsin inhibitor (KTI), and Bowman
      Birk inhibitor (BBI) were not contained in the extracted soybean OBs even by
      neutral pH aqueous extraction. It was clarified that the well-known Gly m Bd 30K
      (Bd 30K), another soybean allergenic protein, was strongly bound to soybean OBs
      through a disulfide bond with 24 kDa oleosin. One steroleosin isoform (41 kDa)
      and two caleosin isoforms (27 kDa, 29 kDa), the integral bioactive proteins, were
      confirmed for the first time in soybean OBs, and a considerable amount of
      calcium, necessary for the biological activities of caleosin, was strongly bound
      to OBs. Unexpectedly, it was found that 24 kDa and 18 kDa oleosins could be
      hydrolyzed by an unknown soybean endoprotease in the extracted soybean OBs, which
      might give some hints for improving the enzyme-assisted aqueous extraction
      processing of soybean free oil. 

PMID- 24028279
TI  - High occurrence of perianal abscess among Bedouin compared to Jews in the
      southern region of Israel.
AB  - BACKGROUND: This study assessed the ethnic differences of perianal abscess
      between Bedouin and the general population in southern region of Israel. Israeli
      born Arabs have much less colorectal cancer than Israeli-born Jews. It is not
      clear whether other colorectal diseases have the same ethnic occurrence. METHOD:
      This is a retrospective case series of patients who had perianal abscess.
      Patients' demographics, managements and course of disease were analyzed. RESULTS:
      Bedouin male constituted 29.7% of all patients, while they constitute only 15.7%
      of the population relative risk of 2.27 (p< 0. 001). 16.4% of the patients
      experienced perianal abscess recurrence. 39% of the males with recurrent abscess
      formation were Bedouin, relative risk of 1.8 (p<0. 001). CONCLUSION: Bedouin
      males have high relative risk to develop perianal abscess. Bedouin males as
      others with first recurrence have high relative risk for recurrence. Thus for
      both groups of patients, there is an indication to operate in order to treat the
      abscess and coexisting fistula.

PMID- 24028280
TI  - Floating microspheres of carvedilol as gastro retentive drug delivery system:
      3(2) full factorial design and in vitro evaluation.
AB  - CONTEXT: Designing a sustained release system for Carvedilol to increase its
      residence time in the stomach. OBJECTIVE: Preparation of floating microsphere by
      the emulsion solvent diffusion method, studying the effect of various process
      parameters and optimize the formulation using full factorial design. METHODS:
      Different microsphere formulations were prepared by varying the ratio
      ethanol:dichloromethane (1:0 to 1:1.5), ethyl cellulose:hydroxypropyl methyl
      cellulose and stirring speed (800-1600 rpm). The effect of these variables on
      particle size, encapsulation parameters, surface topography, in vitro
      floatability and drug release were evaluated. RESULTS: 3(2) full factorial design
      was used for the optimization of the formulation. Drug entrapment efficiency,
      particle size and in vitro drug release were dependent on concentration of ethyl
      cellulose and stirring speed. Microspheres remained buoyant for more than 10 h
      and showed sustained release of the drug. CONCLUSION: Floating microspheres of
      Carvedilol with good floating ability and sustained release were developed.

PMID- 24028281
TI  - Utilization of assistive technology by persons with physical disabilities: an
      examination of predictive factors by race.
AB  - PURPOSE: Examine the relationship between race, use of assistive technology (AT),
      gender, educational attainment, income, employment status and access to health
      care. METHODS: Data were analyzed from the national Behavioral Risk Factor
      Surveillance System (BRFSS) collected in USA in 2007. Descriptive statistics and
      logistic regression were performed. RESULTS: Among those who used AT, more
      European Americans (EAs) were educated, employed, made >$25,000 per year and had
      better access to health coverage. In contrast, more African Americans (AAs) who
      used AT were less educated, unemployed, made <$25,000 per year and had worse
      health coverage. Overall, AAs used AT more than EAs. The trend was consistent
      with predictive factors. AAs were 29% more likely to use AT compared to EAs. For
      EAs and AAs, predictors for use of AT were age, gender, education, employment
      status, income, health coverage and medical costs. CONCLUSIONS: Racial
      differences between AAs and EAs were observed in the use of AT by persons with
      physical disabilities based on age, gender, education, employment status, income
      levels, health care coverage and medical costs. Even though EAs and AAs had the
      same predictors, there were racial differences in the magnitude of the
      predictors.

PMID- 24028282
TI  - Women with fibromyalgia's experience with three motion-controlled video game
      consoles and indicators of symptom severity and performance of activities of
      daily living.
AB  - PURPOSE: Little is known of Motion-Controlled Video Games (MCVGs) as an
      intervention for people with chronic pain. The aim of this study was to explore
      the experience women with fibromyalgia syndrome (FMS) had, using commercially
      available MCVGs; and to investigate indicators of symptom severity and
      performance of activities of daily living (ADL). METHOD: Of 15 female
      participants diagnosed with FMS, 7 completed a program of five sessions with
      Nintendo Wii (Wii), five sessions with PlayStation 3 Move (PS3 Move) and five
      sessions with Microsoft Xbox Kinect (Xbox Kinect). Interviews were conducted at
      baseline and post-intervention and were supported by data from observation and
      self-reported assessment. RESULTS: Participants experienced play with MCVGs as a
      way to get distraction from pain symptoms while doing fun and manageable
      exercise. They enjoyed the slow pace and familiarity of Wii, while some
      considered PS3 Move to be too fast paced. Xbox Kinect was reported as the best
      console for exercise. There were no indication of general improvement in symptom
      severity or performance of ADL. CONCLUSION: This study demonstrated MCVG as an
      effective healthcare intervention for the women with FMS who completed the
      program, with regards to temporary pain relief and enjoyable low impact exercise.
      Implications for Rehabilitation Exercise is recommended in the management of
      fibromyalgia syndrome (FMS). People with FMS often find it counterintuitive to
      exercise because of pain exacerbation, which may influence adherence to an
      exercise program. Motion-controlled video games may offer temporary pain relief
      and fun low impact exercise for women with FMS.

PMID- 24028283
TI  - The impact of nutritional status, physical function, comorbidity and early versus
      late start in dialysis on quality of life in older dialysis patients.
AB  - BACKGROUND: For the majority of the older patients in dialysis, the treatment
      will be lifelong. Thus, quality of life (QoL) is a crucial outcome. Our aim was
      to assess the QoL of older Norwegian dialysis patients and to investigate the
      impact of early (estimated glomerular filtration rate, eGFR >=10 mL/min) versus
      late (eGFR <10 mL/min) start in dialysis, comorbidity, nutritional status and
      physical capacity. METHODS: A self-report questionnaire including SF-36 (QoL) and
      the Subjective Global Assessment (SGA; nutritional status) was mailed to all
      patients (n = 320) >=75 years registered in the Norwegian Renal Registry (NRR) as
      being in dialysis by September 2009. Reply was received from 233 patients (73%).
      Medical data including comorbidities and eGFR at dialysis start (obtained for 194
      patients) were retrieved from the NRR. Functional capacity was determined from
      the SGA. RESULTS: Compared to reports from younger dialysis patients, our
      patients scored poorer on all SF-36 subscales. Early start in dialysis was
      registered for 52 patients, 142 patients started late, 51.4% were well nourished
      (SGA A), 32.3% moderately malnourished (SGA B) and 16.4% were severely
      malnourished (SGA C). No significant association between any SF-36 scores and
      early versus late start, nutritional status or comorbidity was found. Better
      physical function was significantly associated with better scores on all SF-36
      scales. CONCLUSIONS: Our results indicate that physical function is important to
      all QoL aspects. Increased focus on physical rehabilitation seems pertinent.
      Early start of dialysis treatment was not associated with better long term QoL
      scores.

PMID- 24028284
TI  - Does uncontrolled cardiac death for organ donation raise ethical questions? An
      opinion survey.
AB  - BACKGROUND: Organ donation after uncontrolled cardiac death raises complex
      ethical issues. We conducted a survey in a large hospital staff population,
      including caregivers and administrators, to determine their ethical viewpoints
      regarding organ donation after uncontrolled cardiac death. METHODS: Multicenter
      observational survey using a questionnaire, including information on the
      practical modalities of the procedure. Respondents were asked to answer 15
      detailed ethical questions corresponding to different ethical issues raised in
      the literature. Ethical concerns was defined when respondents expressed ethical
      concerns in their answers to at least three of nine specifically selected ethical
      questions. RESULTS: One thousand one hundred ninety-six questionnaires were
      received, and 1057 could be analysed. According to our definition, 573
      respondents out of 1057 (54%) had ethical concerns with regard to donation after
      cardiac death and 484 (46 %) had no ethical concerns. Physicians (55%) and
      particularly junior intensivists (65%) tended to have more ethical issues than
      nurses (52%) and hospital managers (37%). Junior intensivists had more ethical
      issues than senior intensivists (59%), emergency room physicians (46%) and
      transplant specialists (43%). CONCLUSION: Only 46% of hospital-based caregivers
      and managers appear to accept easily the legitimacy of organ donation after
      cardiac death. A significant number of respondents especially intensivists,
      expressed concerns over the dilemma between the interests of the individual and
      those of society. These results underline the need to better inform both
      healthcare professionals and the general population to help to the development of
      such procedure.

PMID- 24028286
TI  - Making sense of complex data: a mapping process for analyzing findings of a
      realist review on guideline implementability.
AB  - BACKGROUND: Realist reviews offer a rigorous method to analyze heterogeneous data
      emerging from multiple disciplines as a means to develop new concepts, understand
      the relationships between them, and identify the evidentiary base underpinning
      them. However, emerging synthesis methods such as the Realist Review are not well
      operationalized and may be difficult for the novice researcher to grasp. The
      objective of this paper is to describe the development of an analytic process to
      organize and synthesize data from a realist review. METHODS: Clinical practice
      guidelines have had an inconsistent and modest impact on clinical practice, which
      may in part be due to limitations in their design. This study illustrates the
      development of a transparent method for organizing and analyzing a complex data
      set informed by a Realist Review on guideline implementability to better
      understand the characteristics of guidelines that affect their uptake in practice
      (e.g., clarity, format). The data organization method consisted of 4 levels of
      refinement: 1) extraction and 2) organization of data; 3) creation of a
      conceptual map of guideline implementability; and 4) the development of a
      codebook of definitions. RESULTS: This new method is comprised of four steps:
      data extraction, data organization, development of a conceptual map, and
      operationalization vis-a-vis a codebook. Applying this method, we extracted 1736
      guideline attributes from 278 articles into a consensus-based set of categories,
      and collapsed them into 5 core conceptual domains for our guideline
      implementability map: Language, Format, Rigor of development, Feasibility,
      Decision-making. CONCLUSIONS: This study advances analysis methods by offering a
      systematic approach to analyzing complex data sets where the goals are to
      condense, organize and identify relationships.

PMID- 24028285
TI  - Real-time cardiovascular magnetic resonance at 1.5 T using balanced SSFP and 40
      ms resolution.
AB  - BACKGROUND: While cardiovascular magnetic resonance (CMR) commonly employs ECG
      synchronized cine acquisitions with balanced steady-state free precession (SSFP)
      contrast at 1.5 T, recent developments at 3 T demonstrate significant potential
      for T1-weighted real-time imaging at high spatiotemporal resolution using
      undersampled radial FLASH. The purpose of this work was to combine both ideas and
      to evaluate a corresponding real-time CMR method at 1.5 T with SSFP contrast.
      METHODS: Radial gradient-echo sequences with fully balanced gradients and at
      least 15-fold undersampling were implemented on two CMR systems with different
      gradient performance. Image reconstruction by regularized nonlinear inversion
      (NLINV) was performed offline and resulted in real-time SSFP CMR images at a
      nominal resolution of 1.8 mm and with acquisition times of 40 ms. RESULTS:
      Studies of healthy subjects demonstrated technical feasibility in terms of
      robustness and general image quality. Clinical applicability with access to
      quantitative evaluations (e.g., ejection fraction) was confirmed by preliminary
      applications to 27 patients with typical indications for CMR including
      arrhythmias and abnormal wall motion. Real-time image quality was slightly lower
      than for cine SSFP recordings, but considered diagnostic in all cases.
      CONCLUSIONS: Extending conventional cine approaches, real-time radial SSFP CMR
      with NLINV reconstruction provides access to individual cardiac cycles and allows
      for studies of patients with irregular heartbeat.

PMID- 24028287
TI  - RAND Report on Workplace Wellness: what employers must know.

PMID- 24028288
TI  - Patient retention of training in self-administration of intravenous antibiotic
      therapy in an outpatient parenteral antibiotic therapy service.
AB  - AIMS AND OBJECTIVES: To assess patient retention of initial training on
      completion of self-administration of a prolonged course of intravenous therapy.
      BACKGROUND: Outpatient parenteral antibiotic therapy is being used increasingly
      in the UK, and patients requiring prolonged antibiotic courses may be trained to
      self-administer therapy. DESIGN: Prospective clinical evaluation. METHODS:
      Patients self-administering parenteral antibiotic therapy through the Sheffield
      outpatient parenteral antibiotic therapy service were assessed when nearing
      completion of therapy for correct technique in five key areas of proficiency
      using a scoring system. RESULTS: Twenty-nine patients and nine carers were
      reassessed, at a median interval of 35 days after completion of the initial
      training package. Of these, 35 of 38 were fully competent in all areas. Three
      patients showed incomplete retention of their initial training. All made errors
      relating to use of sterile technique. CONCLUSIONS: Overall retention of training
      was excellent, and this supports earlier reports that patient-administered
      outpatient parenteral antibiotic therapy is as safe as nurse-administered
      therapy. However, this study highlighted a small number of patients or carers who
      were not fully competent at maintaining sterile technique, and as a result, the
      protocol for training patients has been altered. RELEVANCE TO CLINICAL PRACTICE:
      In this study, we assess patients' ability to maintain safe self-administration
      of therapy over a period of time. Patients are increasingly involved and engaged
      in their own health care, and this study provides a novel approach to assessing
      their competence in practical procedures.

PMID- 24028290
TI  - Robust cuprous phenanthroline sensitizer for solar hydrogen photocatalysis.
AB  - The Cu(I) metal-to-ligand charge-transfer complex, [Cu(dsbtmp)2](+) (dsbtmp = 2,9
      di(sec-butyl)-3,4,7,8-tetramethyl-1,10-phenanthroline), exhibits outstanding
      stability as a visible-light-absorbing photosensitizer in hydrogen-evolving
      homogeneous photocatalysis. In concert with the Co(dmgH)2(py)Cl water reduction
      catalyst and N,N-dimethyl-p-toluidine sacrificial donor in 1:1 H2O:CH3CN, this
      Cu(I) sensitizer remains active even after 5 days of visible-light-pumped
      (lambdaex = 452 +/- 10 nm) hydrogen evolution catalysis. Deuteration studies
      illustrate that the hydrogen produced from this composition does indeed originate
      from aqueous protons. 

PMID- 24028291
TI  - Phylogenetic resolution power of microsatellites and various single-nucleotide
      polymorphism types assessed in 10 divergent chicken populations.
AB  - There has been some debate over the question of which types of DNA variation are
      most appropriate to accurately reconstruct evolutionary events. We compared the
      capacity of microsatellites (STRs) and various types of single-nucleotide
      polymorphism (SNP) loci in the chicken genome. The SNP types differ in their
      location: in exons, introns and promoters. Genetic distances between all possible
      pairs of 10 populations were calculated for each marker type. STR loci, which are
      much more polymorphic than are SNPs, are considered to have occurred at recent
      time compared with old evolutionary events of SNPs. Using structure software, STR
      loci assigned individuals to their population much more correctly than did any
      other marker types, whereas SNPs at promoter regions gave the poorest ascription.
      Furthermore, 29 STR markers were even better than all 152 SNPs together. Ancient
      evolutionary events that produced genetic differences between the most distant
      populations such as Red Jungle Fowl and domestic chicken were detected better by
      exons and introns than by STR loci and promoters. The significant interactions
      found between marker types and populations suggest that marker types had
      different phylogenetic histories, possibly related to a different timescale. 

PMID- 24028292
TI  - Heterologous expression and purification of an active human TRPV3 ion channel.
AB  - The transient receptor potential vanilloid 3 (TRPV3) cation channel is widely
      expressed in human tissues and has been shown to be activated by mild
      temperatures or chemical ligands. In spite of great progress in the TRP-channel
      characterization, very little is known about their structure and interactions
      with other proteins at the atomic level. This is mainly caused by difficulties in
      obtaining functionally active samples of high homogeneity. Here, we report on the
      high-level Escherichia coli expression of the human TRPV3 channel, for which no
      structural information has been reported to date. We selected a suitable
      detergent and buffer system using analytical size-exclusion chromatography and a
      thermal stability assay. We demonstrate that the recombinant purified protein
      contains high alpha-helical content and migrates as dimers and tetramers on
      native PAGE. Furthermore, the purified channel also retains its current inducing
      activity, as shown by electrophysiology experiments. The ability to produce the
      TRPV3 channel heterologously will aid future functional and structural studies.

PMID- 24028294
TI  - Echocardiographic and lung ultrasound characteristics in ambulatory patients with
      dyspnea or prior heart failure.
AB  - PURPOSE: Lung ultrasound (LUS) represents a novel, noninvasive method in the
      assessment of extravascular lung water. We investigated the utility of LUS in
      ambulatory subjects with dyspnea or prior heart failure (HF). METHODS: We studied
      81 ambulatory subjects with HF history or dyspnea who underwent transthoracic
      echocardiography (TTE) with LUS of 8 zones. Subjects with heart transplantation
      or pulmonary conditions known to interfere with LUS were excluded. A reviewer
      blinded to the clinical data performed echocardiographic measurements and
      quantified B-lines (reverberation artifacts arising from the pleural line).
      RESULTS: Of 81 subjects, 74 (91%) (median age 66 years, 39% men, median left
      ventricular ejection fraction [LVEF] 54%, 39% with prior HF) had adequate LUS
      images of all 8 zones and were included in the analysis. The number of B-lines
      ranged from 0-12 (median 2). Increased B-lines, analyzed by tertiles, were
      associated with larger left ventricular (LV) end-diastolic (P = 0.036) and end
      systolic diameters (P = 0.026), septal wall thickness (P = 0.009), LV mass index
      (P = 0.001), left atrial (LA) volume index (P = 0.005), tricuspid regurgitation
      (TR) velocity (P = 0.005) and estimated pulmonary artery systolic pressure (PASP)
      (P = 0.003). In a secondary analysis associations between B-lines (not grouped by
      tertiles) and LV mass index, LA volume index, TR velocity and PASP remained
      stable after adjustment for age, gender, BMI and HF history. CONCLUSIONS:
      Sonographic B-lines from LUS are related to measures of LV and LA structure and
      right ventricular pressure in ambulatory patients with dyspnea or prior HF. The
      added clinical and prognostic utility of this imaging modality in ambulatory
      patients warrants further investigation.

PMID- 24028293
TI  - Role of claudin-5 in the attenuation of murine acute lung injury by simvastatin.
AB  - The statins are now recognized to have pleiotropic properties, including
      augmentation of endothelial barrier function. To explore the mechanisms involved,
      we investigated the effect of simvastatin on endothelial cell (EC) tight
      junctions. Western blotting of human pulmonary artery ECs treated with
      simvastatin (5 MUM) confirmed a significant time-dependent increase (16-48 h) in
      claudin-5 protein expression compared with controls, without detectable
      alterations in zonula occludens-1 or occludin. These effects were associated with
      membrane translocation of VE-cadherin, whereas translocation of vascular
      endothelial cadherin (VE-cadherin; silencing RNA) inhibited simvastatin-induced
      claudin-5 up-regulation. Moreover, simvastatin treatment of ECs induced increased
      phosphorylation of both FoxO1 and beta-catenin, transcriptional regulators of
      claudin-5 expression mediated by VE-cadherin. Subsequently, we found no effect of
      claudin-5 silencing on EC barrier protection by simvastatin in response to
      thrombin stimulation, as measured by either transendothelial electrical
      resistance or by EC monolayer flux of FITC-dextran (2,000 kD). However, silencing
      of claudin-5 did significantly attenuate simvastatin-mediated EC barrier
      protection in response to thrombin, as measured by monolayer flux of sodium
      fluorescein (376 Da). Finally, employing a murine model of LPS-induced acute lung
      injury, there was no effect of claudin-5 silencing in vivo (intratracheal
      injection) on bronchoalveolar lavage fluid protein or cell counts, but LPS
      induced lung tissue extravasation of the small molecular weight markers, sodium
      fluorescein and Hochst stain (562 Da), were significantly increased in claudin-5
      silenced animals compared with simvastatin-treated control animals. These
      findings implicate a distinct mechanism underlying size-selective endothelial
      barrier-protective properties of statins, and may ultimately lead to new novel
      therapeutic targets for patients with acute lung injury. 

PMID- 24028295
TI  - Transdermal microemulsions of Glycyrrhiza glabra L.: characterization, stability
      and evaluation of antioxidant potential.
AB  - The purpose of the present study is to formulate Glycyrrhiza glabra root and
      rhizome aqueous ethanolic extract in microemulsion carrier systems intended for
      transdermal delivery of incorporated antioxidant actives, flavonoids and
      polyphenols. The results obtained reveal that the microemulsion system ME3
      possesses optimum properties regarding drug content (flavonoids and polyphenols),
      viscosity, pH, particle size and polydispersity index, zeta potential, stability,
      permeation of actives and hence possesses high in vitro and ex vivo antioxidant
      efficacy. These results indicate also that this microemulsion shows approximately
      13-fold higher ex vivo antioxidant capacity compared with the liquorice extract
      solution. In addition, the proposed microemulsion is simple to dispense, cost
      effective and provides high patient compliance and convenience because of simple
      topical application and avoidance of non-comfortable oral or parenteral
      administration.

PMID- 24028296
TI  - Chronic obstructive pulmonary disease: a risk factor for type 2 diabetes: a
      nationwide population-based study.
AB  - BACKGROUND: Type 2 diabetes mellitus (DM) is a common medical disorder and a
      leading cause of morbidity and mortality worldwide. We investigated whether
      chronic obstructive pulmonary disease (COPD) was the risk factor for type 2
      diabetes in an Asian population. MATERIALS AND METHODS: From Taiwan's National
      Health Insurance Research Database, we collected data from 16,088 patients,
      including 8044 COPD patients and 8044 age- and gender- matched control subjects.
      Cox proportional hazard regression was performed to evaluate independent risk
      factors for type 2 diabetes in all patients and identify risk factors in patients
      with COPD. RESULTS: During the 5.5-year follow-up, patients with COPD were found
      to have a significantly higher rate of incident type 2 diabetes than the control
      group (P < 0.001). COPD was significantly associated with type 2 diabetes hazard
      ratio (HR : 1.41, 1.23-1.63, P < 0.001) after adjusting sex, age, residential
      area, insurance premium, steroid use, hypertriglycemia, hypertension, coronary
      artery disease (CAD) and cerebrovascular disease. Cox regression analysis showed
      that hypertension (HR : 1.55, 1.33-1.80, P < 0.001) and hypertriglycemia (HR :
      1.48, 1.15-1.90, P = 0.002) were important risk factors for type 2 diabetes in
      patients with COPD. CONCLUSIONS: Patients with COPD have a higher risk of type 2
      diabetes compared with control subjects after adjusting for confounding factors
      such as sex, age, residential area, insurance premium, steroid use,
      hypertriglycemia, hypertension, CAD and cerebrovascular disease. Continuous
      surveillance of signals of dysglycemia may be incorporated into care programmes
      for patients with COPD.

PMID- 24028297
TI  - Rationality and effectiveness of transarterial chemoembolization as an initial
      treatment for BCLC B stage HBV-related hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Transarterial chemoembolization (TACE) is recommended as
      standard care for intermediate hepatocellular carcinoma (HCC). We analyse the
      rationality and effectiveness of TACE with BCLC B stage HBV-related HCC in a
      large cohort. METHODS: A total of 1516 patients with BCLC B stage from 7724 HBV
      related HCCs who received TACE as initial treatment were retrospectively studied.
      The treatment response was assessed by the mRECIST criteria. The overall survival
      was calculated with life-table method and compared with the Mantel-Cox test. The
      prognostic factors were assessed using Cox proportional hazards. RESULTS: The 1-,
      3- and 5-year overall survival rates were 84%, 29% and 19% respectively for all
      patients. Alpha-foetoprotein, Child-Pugh classification, tumour size and number
      were independent prognostic factors. The 5-year survival for patients with CR,
      PR, SD and PD were 39%, 19%, 2% and 0%, respectively (P < 0.0001). Child-Pugh A
      liver function (P = 0.002) and smaller tumour (P < 0.0001) were associated with
      CR/PR response. After TACE, the 5-year survival rates for patients who received
      surgical resection, local ablation, repeated TACE and other therapies were 52%,
      29%, 12%, 10% respectively (P < 0.0001). In 328 CR patients, the prognosis of 151
      patients received surgical resection is better than 177 patients not undergo
      liver resection (5-year survival: 52% & 27%, P < 0.0001). CONCLUSIONS:
      Transarterial chemoembolization is a safe and efficacious treatment for BCLC B
      stage HBV-related HCC. A low AFP level, small tumour, low tumour number and good
      liver function predicted good survival. Tumour response after initial TACE, an
      independent prognostic factor of overall survival, was associated with tumour
      extent and influenced subsequent treatment.

PMID- 24028298
TI  - Characteristic profiles among students and junior doctors with specific career
      preferences.
AB  - BACKGROUND: Factors influencing specialty choice have been studied in an attempt
      to find incentives to enhance the workforce in certain specialties. The notion of
      "controllable lifestyle (CL) specialties," defined by work hours and income, is
      gaining in popularity. As a result, many reports advocate providing a 'lifestyle
      friendly' work environment to attract medical graduates. However, little has been
      documented about the priority in choosing specialties across the diverse career
      opportunities.This nationwide study was conducted in Japan with the aim of
      identifying factors that influence specialty choice. It looked for characteristic
      profiles among senior students and junior doctors who were choosing between
      different specialties. METHODS: We conducted a survey of 4th and 6th (final)-year
      medical students and foundation year doctors, using a questionnaire enquiring
      about their specialty preference and to what extent their decision was influenced
      by a set of given criteria. The results were subjected to a factor analysis.
      After identifying factors, we analysed a subset of responses from 6th year
      students and junior doctors who identified a single specialty as their future
      career, to calculate a z-score (standard score) of each factor and then we
      plotted the scores on a cobweb chart to visualise characteristic profiles.
      RESULTS: Factor analysis yielded 5 factors that influence career preference.
      Fifteen specialties were sorted into 4 groups based on the factor with the
      highest z-score: "fulfilling life with job security" (radiology, ophthalmology,
      anaesthesiology, dermatology and psychiatry), "bioscientific orientation"
      (internal medicine subspecialties, surgery, obstetrics and gynaecology, emergency
      medicine, urology, and neurosurgery), and "personal reasons" (paediatrics and
      orthopaedics). Two other factors were "advice from others" and "educational
      experience". General medicine / family medicine and otolaryngology were
      categorized as "intermediate" group because of similar degree of influence from 5
      factors. CONCLUSION: What is valued in deciding a career varies between
      specialties. Emphasis on lifestyle issues, albeit important, might dissuade
      students and junior doctors who are more interested in bioscientific aspects of
      the specialty or have strong personal reasons to pursue the career choice. In
      order to secure balanced workforce across the specialties, enrolling students
      with varied background and beliefs should be considered in the student selection
      process.

PMID- 24028300
TI  - Diabetes in China: prevalence, diagnosis, and control.

PMID- 24028301
TI  - An unusual case of non-pigmenting fixed drug eruptions in a child.

PMID- 24028302
TI  - Analysis of plasma surfactant protein D levels in lung transplant recipients.
AB  - In lung transplant recipients (LTRs), severe clinical complications, such as
      microbial infections of the lung or transplant rejection, may occur. Surfactant
      protein D (SP-D) is a C-type lectin that is mainly produced in alveolar type II
      cells. Plasma SP-D levels are usually low, but may increase when the lung-blood
      barrier is impaired. In this study, we analyzed whether plasma SP-D
      concentrations reflect rejection or infection of the lung allograft. An enzyme
      linked immunosorbent assay was used to measure SP-D levels in plasma samples from
      58 LTRs during intervals without pathologic respiratory findings and during
      episodes of acute cellular rejection (ACR), microbial colonization, and microbial
      pneumonia. Median plasma SP-D levels were significantly increased during episodes
      of microbial pneumonia, but not in the absence of pathologic respiratory
      findings, during microbial colonization, or during ACR up to grade A2-A3 (P <
      0.05). During pneumonia, an increased plasma SP-D level was detected in 60% of
      LTRs and this was further associated with a significantly higher risk for the
      patients to develop stage III bronchiolitis obliterans syndrome (BOS III) or to
      die within the subsequent 6 months after pneumonia (P = 0.0093). All patients
      with a plasma SP-D level of >300 ng/mL during pneumonia developed BOS III and/or
      died within 6 months of follow-up (P = 0.001). The determination of SP-D levels
      in plasma during pneumonia in LTRs may be of prognostic value and warrants
      further evaluation.

PMID- 24028303
TI  - Synthesis and bioactivity evaluation of novel arylimines containing a 3
      aminoethyl-2-[(p-trifluoromethoxy)anilino]-4(3H)-quinazolinone moiety.
AB  - Twenty-seven novel (E)-3-[2-arylideneaminoethyl]-2-[4-(trifluoromethoxy)anilino]
      4(3H)-quinazolinone derivatives were synthesized by reacting various aromatic
      aldehydes with intermediate 6. The target compounds were characterized by (1)H
      NMR, (3)C NMR, IR, and elemental analysis. Bioassay results revealed that some of
      the compounds have strong antifungal activities against six fungi ( Gibberella
      zeae , Fusarium oxysporum , Clematis mandshurica , Paralepetopsis sasakii ,
      Phytophthora infestans , and Sclerotinia sclerotiorum ) and three bacteria (
      Xanthomonas oryzae , tomato bacterial wilt, and tobacco bacterial wilt). Notably,
      these compounds exhibited the highest activity against tomato bacterial wilt and
      X. oryzae, with 50% effective concentration (EC50) values ranging from 45.96 to
      93.31 MUg/mL and from 20.09 to 21.33 MUg/mL, respectively, which are superior to
      those of the commercial antibacterial agents thiodiazole-copper (99.80 MUg/mL)
      and bismerthiazol (92.61 MUg/mL). These results indicate that novel arylimine
      derivatives containing the 4(3H)-quinazolinone moiety can effectively control
      tobacco bacterial wilt, tomato bacterial wilt, and X. oryzae. Evaluation of their
      bactericidal properties in field studies as well as the mechanisms underlying
      their enhanced antibacterial activity should be interesting topics for future
      investigations. 

PMID- 24028299
TI  - Temporal and concentration-dependent effects of oestradiol on neural pathways
      mediating sexual receptivity.
AB  - The acceptance of oestradiol signalling through receptors found in the cell
      membrane, as well as, the nucleus, has provided for a re-examination of the
      timing and location of the actions of oestradiol on neural circuits mediating
      sexual receptivity (lordosis). Oestradiol membrane signalling involves the
      transactivation of metabotrophic glutamate receptors (mGluRs) that transduce
      steroid information through protein kinase C signalling cascades producing rapid
      activation of lordosis-regulating circuits. It has been known for some time that
      oestradiol initially produces an inhibition of the medial preoptic nucleus. We
      have demonstrated that underlying this inhibition is oestradiol acting in the
      arcuate nucleus to induce beta-endorphin release, which inhibits the medial
      preoptic nucleus through a MU-opioid receptor mechanism. This transient
      inhibition is relieved by either subsequent progesterone treatment or longer
      exposure to higher doses of oestradiol to facilitate lordosis behaviour. We
      review recent findings about oestradiol membrane signalling inducing dendritic
      spine formation in the arcuate nucleus that is critical for oestradiol induction
      of sexual receptivity. Moreover, we discuss the evidence that, in addition to
      oestrogen receptor alpha, several other putative membrane oestrogen receptors
      facilitate lordosis behaviour through regulation of the arcuate nucleus. These
      include the GRP30 and the STX activated Gq-mER. Finally, we report on the
      importance of GABA acting at GABAB receptors for oestradiol membrane signalling
      that regulates lordosis circuit activation and sexual receptivity. 

PMID- 24028304
TI  - Attenuation of allergic airway inflammation in a murine model of asthma by
      Licochalcone A.
AB  - CONTEXT: Licochalcone A (Lico A) is a major and biogenetically characteristic
      chalcone isolated from the root of Xinjiang liquorice, Glycyrrhiza inflata.
      OBJECTIVE: We focused on investigating whether Lico A possesses distinct anti
      inflammatory activity on a non-infectious mouse model of asthma, and we aimed to
      elucidate its involvement with the mitogen-activated protein kinases pathway.
      METHODS: BALB/c mice that were sensitized and challenged to ovalbumin (OVA) were
      treated with Lico A (50 mg/kg) 1 h before they were challenged with OVA. RESULTS:
      Our study demonstrated that Lico A may effectively inhibit the increase in T
      helper type 2 cytokines, such as interleukin (IL)-4, IL-5 and IL-13 in
      bronchoalveolar lavage fluid, and reduced serum levels of OVA-specific IgE and
      IgG. Furthermore, Lico A substantially inhibited OVA-induced eosinophilia in lung
      tissue and mucus hyper-secretion by goblet cells in the airway. Meanwhile,
      pretreatment with Lico A resulted in a significant reduction in mRNA expression
      of acidic mammalian chitinase, chitinase 3-like protein 4 (Ym2), E-selectin,
      Muc5ac, CCL11 and CCR3 in lung tissues and airway hyper-responsiveness to
      methacholine. CONCLUSIONS: These findings suggest that Lico A may effectively
      delay the progression of airway inflammation and could be used as a therapy for
      patients with allergic airway inflammation.

PMID- 24028305
TI  - Perioperative anaesthetic practice for head and neck free tissue transfer -- a UK
      national survey.
AB  - BACKGROUND: Anaesthetic management of microvascular head and neck free flap
      surgery is based on physiological principles, but data on how these affect
      clinical outcomes in this challenging group are limited. There are no evidence
      based guidelines available in this area. METHODS: To establish current
      perioperative anaesthetic practice by surveying all UK centres performing head
      and neck free flap surgery. Anaesthetists from 73 centres performing head and
      neck microvascular reconstructive surgery in the UK were asked to complete a
      structured online survey. The survey included general questions, a hypothetical
      clinical scenario with multiple choice questions and questions about
      perioperative management. The main outcomes measured were protocols of pre
      operative assessment, perioperative fluid and blood pressure strategies,
      monitoring and post-operative management. RESULTS: Seventy-three units were
      contacted, and fifty-five responded (75%). Most respondents performed up to two
      cases per month. Opinion was divided as to how best to manage intra-operative
      blood pressure, fluid balance, pre-operative assessment and monitoring. Notably
      52% preferred crystalloid infusion to increase blood pressure, while 35% stated
      crystalloids were contraindicated. CONCLUSIONS: Currently in the UK, anaesthetic
      perioperative management for head and neck free flap transfer is varied,
      reflecting the paucity of high-quality data in this area; but some techniques, in
      particular avoidance of excessive crystalloid use, is associated with improved
      flap outcome.

PMID- 24028306
TI  - Hypertension management algorithm for type 2 diabetic patients applied in primary
      care.
AB  - BACKGROUND: Hypertension frequently coexists with type 2 diabetes (DM), and
      increases the risk of cardiovascular outcomes. The aim of the study was to
      obtain/maintain blood pressure (BP) goals (ADA/JNC 7) according to a stepwise
      algorithm using the medication supplied by the Brazilian government. METHODS: A
      one-year, single-arm interventional study conducted with type 2 diabetes
      patients. Intervention consisted of intensification of lifestyle changes and
      sequential prescription of drugs: diuretic; ACE inhibitors; beta-adrenergic
      blocking agent and calcium channel blocking agent if BP >130/80 mmHg. RESULTS:
      Seventy-eight patients completed the trial. During intervention, the number of
      antihypertensive tablets rose (3.6 +/- 3.5 vs. 5.9 +/- 3.5 pills/patient; p
      <0.001), as the number of antihypertensive classes increased (1.8 +/- 1.0 vs.
      2.70 +/- 1.2; p < 0.01) and the overall drop of BP was 11 mmHg for SBP (145.0 +/-
      22.8 vs. 133.7 +/- 20.9 mmHg; p < 0.01) and 5 mmHg for DBP (78.7 +/- 11.5 vs.
      73.7 +/- 10.5 mmHg; p = 0.001). Although the number of patients with BP in target
      almost doubled [14 (18.7%) vs. 30 (38.5%) p = 0.008], less than 40% of the
      patients achieved the proposed goals. CONCLUSIONS: A BP algorithm applied to type
      2 diabetic and hypertensive patients is able to lower BP, however more than half
      of the patients did not achieve the ADA/JNC 7 targets demonstrating the
      complexity of BP control in this population. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT06260.

PMID- 24028307
TI  - Rescue therapy with sirolimus in a renal transplant recipient with tacrolimus
      induced hepatotoxicity.
AB  - Calcineurin inhibitors at elevated serum concentrations frequently cause mild
      elevation of the liver chemistries. Although rare, severe hepatotoxicity is their
      serious complication. A 54-year-old man with end-stage renal disease due to
      chronic glomerulonephritis without biopsy received a renal allograft from the
      deceased donor. Eleven days after transplantation severe liver injury (AST up to
      421 IU/L, ALT 1242  IU/L, and GGT 212 IU/L) with the serum bilirubin within the
      normal range was recorded. Tacrolimus trough level was 5.5 ng/mL. Liver
      ultrasound and color-Doppler of the portal system were normal. Liver failure
      completely resolved after withdrawal of the calcineurin inhibitor and switch to
      sirolimus. After 9 months of follow-up our patient has excellent graft and liver
      function. Awareness of the possible association of tacrolimus use with
      hepatotoxicity is important to timely discontinuation of the causative agent, and
      to introduce sirolimus as the rescue therapy.

PMID- 24028308
TI  - Cone-like graphene nanostructures: electronic and optical properties.
AB  - : A theoretical study of electronic and optical properties of graphene nanodisks
      and nanocones is presented within the framework of a tight-binding scheme. The
      electronic densities of states and absorption coefficients are calculated for
      such structures with different sizes and topologies. A discrete position
      approximation is used to describe the electronic states taking into account the
      effect of the overlap integral to first order. For small finite systems, both
      total and local densities of states depend sensitively on the number of atoms and
      characteristic geometry of the structures. Results for the local densities of
      charge reveal a finite charge distribution around some atoms at the apices and
      borders of the cone structures. For structures with more than 5,000 atoms, the
      contribution to the total density of states near the Fermi level essentially
      comes from states localized at the edges. For other energies, the average density
      of states exhibits similar features to the case of a graphene lattice. Results
      for the absorption spectra of nanocones show a peculiar dependence on the photon
      polarization in the infrared range for all investigated structures. 

PMID- 24028309
TI  - Evaluation of a modified community based care transitions model to reduce costs
      and improve outcomes.
AB  - BACKGROUND: The Affordable Care Act of 2010 proposed maximum penalty equal to 1%
      of regular Medicare reimbursements which prompted change in how hospitals regard
      30-day readmissions. While several hospital to home transitional care models
      demonstrated a reduction in readmissions and cost savings, programs adapted to
      population needs and existing resources was essential. METHODS: Focusing on
      process and outcomes evaluation, a retrospective analysis of a modified community
      based care transitions program was conducted. RESULTS: In addition to high levels
      of patient satisfaction with the care transitions program, participants'
      confidence with self care was significantly improved. Further, the program
      evaluation demonstrated a 73% reduction in readmissions and an actual Medicare
      cost savings during the 9-month study period of $214,192, excluding the cost to
      administer the program. CONCLUSIONS: While there are several transitional care
      programs in existence, a customized approach is desirable and often required as
      the most cost effective way to manage care transitions and employ evidence based
      policy making. This study established some of the pitfalls when implementing a
      community-based transitional care program and demonstrated encouraging outcomes.

PMID- 24028310
TI  - New tool for patient evaluation of nurse practitioner in primary care settings.
AB  - AIMS AND OBJECTIVES: To validate a tool for patient evaluation of nurse
      practitioners. BACKGROUND: The roles of nurse practitioners in family practice
      settings are health promotion and routine follow-up of patients with chronic
      diseases. So far, several tools for patient evaluation of nurse practitioners
      have been developed. They revealed several dimensions of nurse practitioners'
      work and high levels of patient satisfaction with their work. The studies also
      reported conflicting data on the associations between demographic and other
      variables and the level of nurse practitioners' evaluation by patients. DESIGN: A
      cross-sectional study. METHODS: This study was performed in a sample of seven
      model family medicine practices in Slovenia. We included 30 consecutive adult
      patients in each model family practice aiming at the final sample of 210
      respondents. Patient evaluation of nurse practitioners was assessed using a Nurse
      Practitioner Evaluation Scale. RESULTS: The response rate was 80.9%. Mean total
      score on Nurse Practitioner Evaluation Scale was 87.9 +/- 12.4 points. Cronbach's
      alpha of Nurse Practitioner Evaluation Scale was 0.941. Factor analyses revealed
      three factors: clinical approach factor, comprehensive approach factor and
      patient-centred approach factor. CONCLUSIONS: Nurse Practitioner Evaluation Scale
      proved to be a reliable tool for patient evaluations of nurse practitioners in
      primary care settings. Nurse Practitioner Evaluation Scale can be used in terms
      of a whole scale as well as in terms of three separate subscales. RELEVANCE TO
      CLINICAL PRACTICE: This newly developed tool can be used to monitor quality
      performance of nurse practitioners and to plan quality improvement actions in
      nurse practitioners' performance in primary care settings.

PMID- 24028311
TI  - The political (and physiological) divide: Political orientation, performance
      monitoring, and the anterior cingulate response.
AB  - Our goal was to test a model of sociopolitical attitudes that posits a
      relationship between individual differences in liberal versus conservative
      political orientation and differential levels of anterior cingulate cortex (ACC)
      responsivity. We recorded event-related potentials (ERPs) while participants who
      varied along a unidimensional liberal-conservative continuum engaged in a
      standard Go/NoGo task. We also measured component attitudes of political
      orientation in the form of traditionalism (degree of openness to social change)
      and egalitarianism (a preference for social equality). Generally, participants
      who reported a more liberal political orientation made fewer errors and produced
      larger ACC-generated ERPs (the error-related negativity, or ERN and the NoGo N2).
      This ACC activation, especially as indicated by a larger NoGo N2, was most
      strongly associated with greater preference for social equality. Performance
      accuracy, however, was most strongly associated with greater openness to social
      change. These data are consistent with a social neuroscience view that
      sociopolitical attitudes are related to aspects of neurophysiological
      responsivity. They also indicate that a bidimensional model of political
      orientation can enhance our interpretation of the nature of these associations. 

PMID- 24028313
TI  - Down-modulation of mu-activity through empathic top-down processes.
AB  - Simulation theories argue that humans simulate motor processes of others to gain
      information about intentions and emotional states of others. Mu-suppression is a
      valid electrophysiological correlate of these processes. Mu-activity can be
      measured via electroencephalography (EEG) in the alpha-band (8-13 Hz) above the
      sensorimotor cortex and is suppressed when actions are executed or observed.
      Based on a within-subject design, including 28 participants, it was tested
      whether the processes measured by mu-suppression could be modulated by empathic
      top-down-processes. Participants were asked to take the perspective of two
      actors, telling a story about a sad or neutral life event (video sequences).
      Afterwards, EEG was measured at central (C3, Cz, C4) and occipital (O1, Oz, O2)
      electrodes, while participants observed the actors drinking water (standardized
      video sequences, 8 s duration). Fast fourier transformation showed stronger
      suppression of power in the alpha-range (relative to baseline) at central and
      occipital electrodes while the actor with the sad story was observed relative to
      the actor with the neutral story. Furthermore, measures of state empathy
      correlated positively with the difference of mu-suppression between executed and
      observed movements, an indicator of self-other discrimination. Thus, mirror
      neuron activity measured by mu-suppression is modulated by empathic processes.

PMID- 24028315
TI  - Superconductivity in the narrow-gap semiconductor CsBi4Te6.
AB  - Superconductivity was discovered in the narrow-gap semiconductor CsBi4Te6. A
      superconducting transition around 4.4 K was observed for p-type samples in
      temperature-dependent resistivity and magnetic susceptibility data.
      Stoichiometric CsBi4Te6 is not a superconductor. A remarkably high critical field
      of ~10 T was estimated from the field-dependent resistivity data. The strongly
      anisotropic CsBi4Te6 system is monoclinic and the first member of a larger
      homologous series Cs4[Bi(2n+4)Te(3n+6)] that exhibits unconventional
      superconductivity, suggesting that proper doping of the homologous series may
      create a novel class of superconductors from semiconductors.

PMID- 24028312
TI  - Distinct neural circuits subserve interpersonal and non-interpersonal emotions.
AB  - Emotions elicited by interpersonal versus non-interpersonal experiences have
      different effects on neurobiological functioning in both animals and humans.
      However, the extent to which the brain circuits underlying interpersonal and non
      interpersonal emotions are distinct still remains unclear. The goal of our study
      was to assess whether different neural circuits are implicated in the processing
      of arousal and valence of interpersonal versus non-interpersonal emotions. During
      functional magnetic resonance imaging, participants imagined themselves in
      emotion-eliciting interpersonal or non-interpersonal situations and then rated
      the arousal and valence of emotions they experienced. We identified (1) separate
      neural circuits that are implicated in the arousal and valence dimensions of
      interpersonal versus non-interpersonal emotions, (2) circuits that are implicated
      in arousal and valence for both types of emotion, and (3) circuits that are
      responsive to the type of emotion, regardless of the valence or arousal level of
      the emotion. We found extensive recruitment of limbic (for arousal) and temporal
      parietal (for valence) systems associated with processing of specifically
      interpersonal emotions compared to non-interpersonal ones. The neural bases of
      interpersonal and non-interpersonal emotions may, therefore, be largely distinct.

PMID- 24028316
TI  - Influence of active reminders on oral hygiene compliance in orthodontic patients.
AB  - OBJECTIVE: To determine if text message reminders regarding oral hygiene
      compliance have an influence on the level of compliance within an orthodontic
      population. MATERIALS AND METHODS: In this prospective, randomized, controlled
      clinical trial, 42 orthodontic patients were assigned to a text message or
      control group. Parents of patients assigned to the text message group received a
      reminder text message one weekday each week. Oral hygiene compliance was measured
      using bleeding index (BI), modified gingival index (MGI), and plaque index (PI),
      and visual examination of white spot lesion (WSL) development at baseline (T0),
      two appointments after baseline (T1), and four appointments after baseline (T2).
      RESULTS: BI, MGI, and PI scores were significantly lower in the text message
      group than in the control group at T2. CONCLUSION: A text message reminder system
      is effective for improving oral hygiene compliance in orthodontic patients.

PMID- 24028317
TI  - A systematic investigation and insight into the formation mechanism of bilayers
      of fatty acid/soap mixtures in aqueous solutions.
AB  - Vesicles are the most common form of bilayer structures in fatty acid/soap
      mixtures in aqueous solutions; however, a peculiar bilayer structure called a
      "planar sheet" was found for the first time in the mixtures. In the past few
      decades, considerable research has focused on the formation theory of bilayers in
      fatty acid/soap mixtures. The hydrogen bond theory has been widely accepted by
      scientists to explain the formation of bilayers. However, except for the hydrogen
      bond, no other driving forces were proposed systematically. In this work, three
      kinds of weak interactions were investigated in detail, which could perfectly
      demonstrate the formation mechanism of bilayer structures in the fatty acid/soap
      mixtures in aqueous solutions. (i) The influence of hydrophobic interaction was
      detected by changing the chain length of fatty acid (C(n)H(2n+1)COOH), in which n
      = 10 to 18, the phase behavior was investigated, and the phase region was
      presented. With the help of cryogenic transmission electron microscopy (cryo-TEM)
      observations, deuterium nuclear magnetic resonance ((2)H NMR), and X-ray
      diffraction (XRD) measurements, the vesicles and planar sheets were determined.
      The chain length of C(n)H(2n+1)COOH has an important effect on the physical state
      of the hydrophobic chain, resulting in an obvious difference in the
      viscoelasticity of the solution samples. (ii) The existence of hydrogen bonds
      between fatty acids and their soaps in aqueous solutions was demonstrated by
      Fourier transform infrared (FT-IR) spectroscopy and molecule dynamical
      simulation. From the pH measurements, the pH ranges of the bilayer formation were
      at the pKa values of fatty acids, respectively. (iii) Counterions can be embedded
      in the stern layer of the bilayers and screen the electrostatic repulsion between
      the COO(-) anionic headgroups. FT-IR characterization demonstrated a bidentate
      bridging coordination mode between counterions and carboxylates. The conductivity
      measurements provided the degree of counterion binding (beta = 0.854), indicating
      the importance of the counterions.

PMID- 24028318
TI  - Release of chromium from soils with persulfate chemical oxidation.
AB  - An important part of the evaluation of the effectiveness of persulfate in situ
      chemical oxidation (ISCO) for treating organic contaminants is to identify and
      understand its potential impact on metal co-contaminants in the subsurface.
      Chromium is a redox-sensitive and toxic metal the release of which poses
      considerable risk to human health. The objective of this study was to investigate
      the impact of persulfate chemical oxidation on the release of chromium from three
      soils varying in physical-chemical properties. Soils were treated with
      unactivated and activated persulfate [activated with Fe(II), Fe(II)-EDTA, and
      alkaline pH] at two different concentrations (i.e., 41 mM and 2.1 mM persulfate)
      for 48 h and 6 months and were analyzed for release of chromium. Results show
      that release of chromium with persulfate chemical oxidation depends on the soil
      type and the activation method. Sandy soil with low oxidant demand released more
      chromium compared to soils with high oxidant demand. More chromium was released
      with alkaline pH activation. Alkaline pH and high Eh conditions favor oxidation
      of Cr(III) to Cr(VI), which is the main mechanism of release of chromium with
      persulfate chemical oxidation. Unactivated and Fe(II)-activated persulfate
      decreased pH and at low pH in absence of EDTA chromium release is not a concern.
      These results indicate that chromium release can be anticipated based on the
      given site and treatment conditions, and ISCO system can be designed to minimize
      potential chromium release when treating soils and groundwater contaminated with
      both organic and metal contaminants. 

PMID- 24028319
TI  - Determination of the optimum number of cardiac cycles to differentiate intra
      pulmonary shunt and patent foramen ovale by saline contrast two- and three
      dimensional echocardiography.
AB  - INTRODUCTION: Patent foramen ovale (PFO) and intra-pulmonary shunt (IPS) are
      potential causes of stroke. The most optimum cardiac cycle cutoff for bubbles to
      appear in the left heart on saline contrast transthoracic echocardiography (TTE)
      as criteria to differentiate the 2 entities is unknown. METHODS: Ninety-five
      adult patients had saline contrast transesophageal echocardiography (TEE), two
      dimensional (2D) and 3DTTE. Sensitivity and specificity of each cardiac cycle as
      cutoff to differentiate a PFO and IPS were obtained. RESULTS: Transesophageal
      echocardiography showed IPS in 28 and PFO in 15 patients. If bubbles appeared in
      the left heart within the first 4 cardiac cycles (the 4th cardiac cycle rule) as
      compared to alternate cutoffs, a PFO was most accurately diagnosed by both 2D and
      3DTTE. Bubbles appearing at or after the 5th cardiac cycle most accurately
      determined an IPS. 3D versus 2DTTE had a trend for a higher sensitivity (61% vs.
      36%, P = 0.06), but similar specificity (94% vs. 91%) for IPS. Accuracy of 3DTTE
      was 84% and 2DTTE was 75% (P = 0.08) for IPS. For PFO, 2DTTE sensitivity (87%)
      and specificity (98%) did not differ (P = NS) from that of 3DTTE sensitivity
      (73%) and specificity (100%). CONCLUSIONS: This study demonstrates for the first
      time that the 4th cardiac cycle rule differentiates PFO and IPS most optimally by
      2D and 3DTTE. 3DTTE appears to have higher sensitivity for diagnosing IPS. These
      data suggest that 3DTTE is preferable when IPS is to be diagnosed. Both methods
      are similar for diagnosing PFO.

PMID- 24028320
TI  - Angioedema without urticaria in childhood.
AB  - BACKGROUND: There has been no separate study investigating angioedema without
      urticaria (Aw/oU) exclusively in children so far. The purpose of this study was
      to investigate the frequency, clinical presentation, etiology, management and
      follow-up of Aw/oU in children. METHODS: This is a prospective study that
      included all consecutive patients with a history of Aw/oU referred to our clinic
      between January 2011 and May 2012. A standard diagnostic and therapeutic
      algorithm was applied to all patients. RESULTS: The frequency of Aw/oU was found
      to be 1.6% during the study period. An etiological factor could be found in only
      45 patients (49%). The causes of Aw/oU were infection (21%), allergy (14%),
      thyroid autoimmunity (TA)-related (8%) and nonsteroid anti-inflammatory drug
      hypersensitivity (6%), and idiopathic angioedema (51%). There was no hereditary
      type I, II or acquired type of angioedema or rare syndromes associated with
      Aw/oU. The median follow-up was 16 months (range: 12-30 months). Antihistamine
      prophylaxis was initiated at therapeutic doses in 20 patients with frequently
      recurrent angioedema due to idiopathic and euthyroid TA-related Aw/oU for 3
      months. These patients responded to antihistamine prophylaxis for 3 months. Four
      patients relapsed after cessation of prophylaxis at the end of 3 months.
      Antihistamine prophylaxis was prolonged to 6 months in three patients and to 9
      months in one patient. CONCLUSIONS: Angioedema without urticaria in children is a
      rare condition and no etiology can be identified in half of them. Antihistamine
      treatment alone is sufficient, and prognosis is good in recurrent non hereditary
      cases in a short-term follow-up period.

PMID- 24028321
TI  - Obesity phenotypes and subclinical cardiovascular diseases in a mixed-ancestry
      South African population: a cross-sectional study.

PMID- 24028323
TI  - Paraoxonase 1 and oxidative stress in paediatric non-alcoholic steatohepatitis.
AB  - BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) in children is a
      significant public health concern. Oxidative stress is an important component in
      the pathophysiology of NASH. Several enzymatic antioxidant mechanisms protect the
      liver from oxidative injury. Examination of the expression of these enzymes in
      NASH livers may provide insight on the roles for these antioxidant mechanisms in
      the pathophysiology of NASH. METHODS: The mRNA expression of catalase,
      glutathione peroxidase 1 (GPX1), glutathione reductase (GSR), paraoxonase 1
      (PON1) and other reactive oxygen species-related genes was evaluated by
      microarray and quantitative real-time PCR analyses. The PON1 protein levels were
      evaluated in liver and serum by Western blot analyses. Serum enzymatic activities
      of GPX, GSR and PON1 (paraoxonase and arylesterase activities) were examined.
      RESULTS: NASH livers exhibited elevated mRNA expression of catalase and PON1, but
      not GPX1 or GSR. No difference in serum GPX or GSR activity was detected between
      NASH patients and controls. Elevated expression of PON1 mRNA and protein was
      detected in NASH livers, but serum PON1 protein and activities were not elevated.
      CONCLUSIONS: Elevated expression of catalase and PON1 suggests protective roles
      for these antioxidants in NASH livers. Given the importance of oxidative stress
      in the pathophysiology of NASH, future studies focusing on these enzymes could
      identify important targets for therapeutic or preventive interventions for NASH
      patients.

PMID- 24028324
TI  - Peanut Allergen Threshold Study (PATS): validation of eliciting doses using a
      novel single-dose challenge protocol.
AB  - BACKGROUND: The eliciting dose (ED) for a peanut allergic reaction in 5% of the
      peanut allergic population, the ED05, is 1.5 mg of peanut protein. This ED05 was
      derived from oral food challenges (OFC) that use graded, incremental doses
      administered at fixed time intervals. Individual patients' threshold doses were
      used to generate population dose-distribution curves using probability
      distributions from which the ED05 was then determined. It is important to
      clinically validate that this dose is predictive of the allergenic response in a
      further unselected group of peanut-allergic individuals. METHODS/AIMS: This is a
      multi-centre study involving three national level referral and teaching centres.
      (Cork University Hospital, Ireland, Royal Children's Hospital Melbourne,
      Australia and Massachusetts General Hospital, Boston, U.S.A.) The study is now in
      process and will continue to run until all centres have recruited 125
      participates in each respective centre.A total of 375 participants, aged 1-18
      years will be recruited during routine Allergy appointments in the centres. The
      aim is to assess the precision of the predicted ED05 using a single dose (6 mg
      peanut = 1.5 mg of peanut protein) in the form of a cookie. Validated Food
      Allergy related Quality of Life Questionnaires-(FAQLQ) will be self-administered
      prior to OFC and 1 month after challenge to assess the impact of a single dose
      OFC on FAQL. Serological and cell based in vitro studies will be performed.
      CONCLUSION: The validation of the ED05 threshold for allergic reactions in peanut
      allergic subjects has potential value for public health measures. The single dose
      OFC, based upon the statistical dose-distribution analysis of past challenge
      trials, promises an efficient approach to identify the most highly sensitive
      patients within any given food-allergic population.

PMID- 24028325
TI  - Benefit sharing: an exploration on the contextual discourse of a changing
      concept.
AB  - BACKGROUND: The concept of benefit sharing has been a topical issue on the
      international stage for more than two decades, gaining prominence in
      international law, research ethics and political philosophy. In spite of this
      prominence, the concept of benefit sharing is not devoid of controversies related
      to its definition and justification. This article examines the discourses and
      justifications of benefit sharing concept. DISCUSSION: We examine the discourse
      on benefit sharing within three main spheres; namely: common heritage of
      humankind, access and use of genetic resources according to the Convention on
      Biological Diversity (CBD), and international clinical research. Benefit sharing
      has changed from a concept that is enshrined in a legally binding regulation in
      the contexts of common heritage of humankind and CBD to a non-binding regulation
      in international clinical research. Nonetheless, there are more ethical
      justifications that accentuate benefit sharing in international clinical research
      than in the contexts of common heritage of humankind and the CBD. SUMMARY: There
      is a need to develop a legal framework in order to strengthen the advocacy and
      decisiveness of benefit sharing practice in international health research. Based
      on this legal framework, research sponsors would be required to provide a minimum
      set of possible benefits to participants and communities in research. Such legal
      framework on benefit sharing will encourage research collaboration with local
      communities; and dispel mistrust between research sponsors and host communities.
      However, more research is needed, drawing from other international legal
      frameworks, to understand how such a legal framework on benefit sharing can be
      successfully formulated in international health research.

PMID- 24028326
TI  - Long-circulating nanoliposomes (LCNs) sustained delivery of baicalein (BAI) with
      desired oral bioavailability in vivo.
AB  - Long-circulating nanoliposomes (LCNs) containing Baicalein (BAI) were prepared by
      diethyl ether injection method in this paper. Using soybean phosphatidylcholine
      (SPC) and cholesterol (CHOL) as the carrier ingredients, BAI-loaded LCNs were
      formulated in optimized condition with encapsulation efficiency (EE) of 41.5+/
      4.77%. The average diameter of BAI-loaded LCNs was ~709 nm determined by dynamic
      light scattering (PDI 0.43). Drug storage stability study showed that BAI-loaded
      LCNs were highly stable in phosphate-buffered saline (PBS, pH 7.4) at 4  degrees
      C. Additionally, the pharmacokinetic behaviors of BAI-loaded LCNs were studied
      using Kunming mice as experimental animals. Parallelly, free BAI solution was
      studied as control. As expected, it is found that LCNs-encapsulated BAI yields
      greater BAI oral bioavailability with 4.52 times of free BAI. These results
      suggest the potential applications of LCNs for the delivery of BAI.

PMID- 24028327
TI  - Identification and polymorphism discovery of the cathelicidins, Lf-CATHs in ranid
      amphibian (Limnonectes fragilis).
AB  - To protect themselves against the invasion of microorganisms, amphibians,
      especially the Rana frogs, are possibly equipped with complex combinations of
      antimicrobial peptides (AMPs). The two major AMP families, ranid skin secretion
      AMPs and cathelicidins might together constitute the host innate immune system of
      amphibians. Cathelicidins are a group of cationic peptides found in leukocytes
      and epithelial cells, and they play a central role in the early innate immune
      defense found in virtually all species of mammals. However, they have rarely been
      reported from amphibians. Here, we report the identification and discovery of
      polymorphism cathelicidins in Limnonectes fragilis. The expression profile
      indicated high cathelicidin transcript levels in frog spleen, liver and kidney,
      but lower levels in lung, skin and stomach. According to the amphibian's unique
      proteolytic pattern, R125 and L121 of the prepropeptides are predicted to be the
      processing positions for protease to generate the mature peptides, Lf-CATH1 and 
      2, respectively. Both consist of 30 amino acid residues, of which two were
      cysteines positionally conserved among a few known amphibian cathelicidins.
      Homology modeling analysis revealed that Lf-CATH1 and -2 adopt a tertiary
      structure with a mostly alpha helix that is representative of small cationic
      cathelicidin family peptides. Recombinant Lf-CATH1 (rLf-CATH1) was produced in
      Escherichia coli. Synthetic Lf-CATH1 and -2 displayed potent antimicrobial
      activities in vitro against a broad spectrum of microorganisms, including
      standard and clinically isolated drug-resistant strains, while showing
      neglectable hemolysis and cytotoxicities.

PMID- 24028328
TI  - Identifying the superior measure of rapid fibrosis for predicting premature
      cirrhosis after liver transplantation for hepatitis C.
AB  - BACKGROUND: Hepatitis C virus (HCV) recurrence post liver transplant is
      universal, with a subgroup of patients developing rapid hepatic fibrosis. Various
      clinical definitions of rapid fibrosis (RF) have been used to identify risks for
      rapid progression, but their comparability and efficacy at predicting adverse
      outcomes has not been determined. METHODS: Retrospective data analysis was
      conducted on 100 adult patients with HCV who underwent liver transplantation at a
      single center. We measured year 1 fibrosis progression (RF defined as METAVIR F
      score >= 1 at 1-year liver biopsy), time to METAVIR F2-stage fibrosis, and
      fibrosis rate (calculated using liver biopsies graded by METAVIR scoring F0-4;
      fibrosis rate = fibrosis stage/year post transplant). RF was defined as >= 0.5
      units/year. RESULTS: Multivariate analysis revealed that donor age and peak HCV
      viral load were significant risks for RF, when fibrosis rate was used to define
      RF. Advanced donor age was a risk for rapid progression to F2-stage fibrosis,
      whereas genotype 2 or 3 HCV infection was protective. Fibrosis rate had the
      strongest correlation with time to cirrhosis development (P < 0.0001, r = -0.76)
      and was the most accurate predictor of rapid graft cirrhosis (P < 0.0001, area
      under the curve 0.979, sensitivity 100%, specificity 94%). CONCLUSION: Different
      measures of RF progression identify different risks for RF and are not directly
      comparable. Fibrosis rate was the most accurate predictor of rapid graft
      cirrhosis.

PMID- 24028329
TI  - Reply: To PMID 23252861.

PMID- 24028331
TI  - The impact of chronic hepatitis C on resource utilisation and in-patient
      mortality for Medicare beneficiaries between 2005 and 2010.
AB  - BACKGROUND: As baby boomers age, chronic hepatitis C (CHC) will become
      increasingly important in Medicare eligible group. AIM: To evaluate trends in
      Medicare resource utilisation for CHC. METHODS: We analysed the Medicare in
      patient and out-patient data from 2005 to 2010. For each patient, all claims with
      CHC as a principal diagnosis were added up and yearly CHC-related spending was
      calculated. RESULTS: A total of 48,880 out-patient claims for 21,655 CHC patients
      and 4884 hospital admission claims for 3092 patients were included. The number of
      in-patient (1.5-1.6/year) or out-patient (2.2-2.3/year) visits per patient did
      not change over time, nor did the demographic characteristics of the CHC
      population. The majority of this population was eligible for Medicare based on
      disability and the average number of diagnoses per in-patient claim (from 8.11 in
      2005 to 8.60 in 2010) and per out-patient claim (from 2.18 in 2005 to 2.71 in
      2010) increased (both P < 0.0001). The average total yearly spending per patient
      increased in the out-patient setting from $488 in 2005 to $584 in 2010 (P =
      0.0132) and did not change in the in-patient setting (from $22,245 in 2005 to
      $23,383 in 2010, P = 0.14). In the multivariate analysis, the number of diagnoses
      and conditions per claim and the number of in-patient or out-patient procedures
      per year were the important independent predictors of increased resource
      utilisation. CONCLUSIONS: Most Medicare beneficiaries with chronic hepatitis C
      who sought in-patient or out-patient care in 2005-2010 had received Medicare for
      disability. Although the total resource utilisation did not change, the
      proportion of patient's responsibility increased.

PMID- 24028330
TI  - Potential of human fetal chorionic stem cells for the treatment of osteogenesis
      imperfecta.
AB  - Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset,
      characterized by brittle bones in response to abnormal collagen composition.
      There is presently no cure for OI. We previously showed that human first
      trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI
      model (oim mice) improved the phenotype. However, the clinical use of fetal MSC
      is constrained by their limited number and low availability. In contrast, human
      fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions
      and isolated in high numbers from the placenta during ongoing pregnancy. Here, we
      show that intraperitoneal injection of e-CSC in oim neonates reduced fractures,
      increased bone ductility and bone volume (BV), increased the numbers of
      hypertrophic chondrocytes, and upregulated endogenous genes involved in
      endochondral and intramembranous ossification. Exogenous cells preferentially
      homed to long bone epiphyses, expressed osteoblast genes, and produced collagen
      COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness
      and BV by directly differentiating to osteoblasts and indirectly stimulating host
      chondrogenesis and osteogenesis. In conclusion, the placenta is a practical
      source of stem cells for the treatment of OI. 

PMID- 24028333
TI  - MHC class I expression dependent on bacterial infection and parental factors in
      whitefish embryos (Salmonidae).
AB  - Ecological conditions can influence not only the expression of a phenotype, but
      also the heritability of a trait. As such, heritable variation for a trait needs
      to be studied across environments. We have investigated how pathogen challenge
      affects the expression of MHC genes in embryos of the lake whitefish Coregonus
      palaea. In order to experimentally separate paternal (i.e. genetic) from maternal
      and environmental effects, and determine whether and how stress affects the
      heritable variation for MHC expression, embryos were produced in full-factorial
      in vitro fertilizations, reared singly, and exposed at 208 degree days (late-eyed
      stage) to either one of two strains of Pseudomonas fluorescens that differ in
      their virulence characteristics (one increased mortality, while both delayed
      hatching time). Gene expression was assessed 48 h postinoculation, and virulence
      effects of the bacterial infection were monitored until hatching. We found no
      evidence of MHC class II expression at this stage of development. MHC class I
      expression was markedly down-regulated in reaction to both pseudomonads. While
      MHC expression could not be linked to embryo survival, the less the gene was
      expressed, the earlier the embryos hatched within each treatment group, possibly
      due to trade-offs between immune function and developmental rate or further
      factors that affect both hatching timing and MHC expression. We found significant
      additive genetic variance for MHC class I expression in some treatments. That is,
      changes in pathogen pressures could induce rapid evolution in MHC class I
      expression. However, we found no additive genetic variance in reaction norms in
      our study population.

PMID- 24028332
TI  - Oestrogen-independent circadian clock gene expression in the anteroventral
      periventricular nucleus in female rats: possible role as an integrator for
      circadian and ovarian signals timing the luteinising hormone surge.
AB  - Periodic ovulation in rats, mice and hamsters is the result of a surge in
      luteinising hormone (LH) that depends on circadian gating signals emerging from
      the master circadian clock within the suprachiasmatic nucleus (SCN) and rising
      ovarian oestrogen levels. These two signals converge into the anteroventral
      periventricular nucleus (AVPV) and lead to the release of kisspeptin, which is
      responsible for surges of gonadotrophin-releasing hormone and, in turn, of LH
      release. How the AVPV integrates circadian and reproductive signals remains
      unclear. In the present study, we show that the female rat AVPV itself shows
      circadian oscillations in the expression of the clock genes PER1 and BMAL1, which
      lie at the core circadian clockwork of mammals. In ovariectomised females treated
      with oestradiol (E2), these oscillations are in synchrony with the AVPV rhythmic
      expression of the KISS1 gene and the gene that codes for the arginine-vasopressin
      (AVP) receptor AVPr1a. Although clock gene oscillations are independent of
      oestrogen levels, circadian expression of Kiss1 and Avpr1a (also referred to as
      V1a) mRNA is blunted and absent, respectively, in ovariectomised animals without
      E2 replacement. Because AVP is considered to be a critical SCN transmitter to
      gate the LH surge, our data suggest that there is a circadian oscillator located
      in the AVPV, and that such a putative oscillator could, in an oestrogen-dependent
      manner, time the sensitivity to circadian signals emerging from the SCN and the
      release of kisspeptin.

PMID- 24028334
TI  - Isolation of Streptococcus agalactiae and an aquatic birnavirus from doctor fish
      Garra rufa L.
AB  - BACKGROUND: The doctor fish, Garra rufa, has become increasingly popular as a
      treatment for skin disorders and for pedicures in recent years. Despite this
      there is very little information available regarding the welfare of these fish
      and the range of potential pathogens they may carry. In this study, a group of
      fish suffering from post-transport mortalities were examined and the isolated
      pathogens identified. FINDINGS: Group B Streptococcus agalactiae was isolated
      from kidney swabs of the fish and found to be resistant to a number of
      antibiotics. In addition to this, a fish virus belonging to the aquabirnavirus
      group, serogroup C was isolated for the first time in Ireland. However, no
      clinical signs of disease typical of bacterial or viral infections were observed
      in any fish examined. CONCLUSIONS: As no clinical signs of disease attributable
      to either of the pathogens identified were found it was concluded that the
      mortalities were most likely due to transport related stress exacerbated by the
      presence of the pathogens. Further work is required to assess the suitability of
      current transport strategies and to examine the potential risk associated with
      the transport of live ornamental fish.

PMID- 24028335
TI  - Density functional theory assessment of molecular structures and energies of
      neutral and anionic Al(n) (n = 2-10) clusters.
AB  - We report the results of a benchmarking study on hybrid, hybrid-meta, long-range
      corrected, meta-generalized gradient approximation (meta-GGA), and GGA density
      functional theory (DFT) methods for aluminum (Al) clusters. A range of DFT
      functionals, such as B3LYP, B1B95, PBE0, mPW1PW91, M06, M06-2X, omegaB97X,
      omegaB97XD, TPSSh, BLYP, PBE, mPWPW91, M06-L, and TPSS, have been used to
      optimize the molecular structures and calculate the vibrational frequencies and
      four energetic parameters for neutral and anionic Al(n) (n = 2-10) clusters. The
      performances of these functionals are assessed systematically by calculating the
      vertical ionization energy for neutral Al clusters and the vertical electron
      detachment energy for anionic Al clusters, along with the cohesive energy and
      dissociation energy. The results are compared with the available experimental and
      high-level ab initio calculated results. The calculated results showed that the
      PBE0 and mPW1PW91 functionals generally provide better results than the other
      functionals studied. TPSS can be a good choice for the calculations of very large
      Al clusters. On the other hand, the B3LYP, BLYP, and M06-L functionals are in
      poor agreement with the available experimental and theoretical results. The
      calculated results suggest that the hybrid DFT functionals like B3LYP do not
      always provide better performance than GGA functionals.

PMID- 24028336
TI  - Multiregional input-output model for the evaluation of Spanish water flows.
AB  - We construct a multiregional input-output model for Spain, in order to evaluate
      the pressures on the water resources, virtual water flows, and water footprints
      of the regions, and the water impact of trade relationships within Spain and
      abroad. The study is framed with those interregional input-output models
      constructed to study water flows and impacts of regions in China, Australia,
      Mexico, or the UK. To build our database, we reconcile regional IO tables,
      national and regional accountancy of Spain, trade and water data. Results show an
      important imbalance between origin of water resources and final destination, with
      significant water pressures in the South, Mediterranean, and some central
      regions. The most populated and dynamic regions of Madrid and Barcelona are
      important drivers of water consumption in Spain. Main virtual water exporters are
      the South and Central agrarian regions: Andalusia, Castile-La Mancha, Castile
      Leon, Aragon, and Extremadura, while the main virtual water importers are the
      industrialized regions of Madrid, Basque country, and the Mediterranean coast.
      The paper shows the different location of direct and indirect consumers of water
      in Spain and how the economic trade and consumption pattern of certain areas has
      significant impacts on the availability of water resources in other different and
      often drier regions. 

PMID- 24028340
TI  - Discordant Doppler right heart catheterization pulmonary artery systolic
      pressures: importance of pulmonary capillary wedge pressure.
AB  - BACKGROUND: Although the echo Doppler (D) estimation of pulmonary artery systolic
      pressure (PASP) was initially highly correlated with right heart catheterization
      (RHC), recent D-RHC studies have questioned its accuracy. The aim of this study
      was to reevaluate this relationship and to determine possible explanations for
      disparate D-RHC results. METHODS: We retrospectively identified all patients at
      one institution who underwent RHC and had an echocardiogram within the prior
      month. Echocardiographic and catheterization hemodynamic factors were evaluated
      by regression and Bland-Altman analysis. RESULTS: Of 69 patients, 52 (75.4%) had
      estimable D-PASP. D-RHC PASP r = 0.62 and 51.9% had a PASP difference >10 mmHg,
      comparable to other recent studies. The D-RHC difference correlated with
      pulmonary capillary wedge pressure (PCWP) (r = -0.60, P < 0.001) and right atrial
      pressure (r = -0.43, P = 0.002). Multivariate analysis including wedge pressure
      improved the relation between D and RHC for PASP (r = 0.86). These results were
      little changed using only the respective RV-RA pressure gradients from D and RHC.
      CONCLUSION: Pulmonary capillary wedge pressure appears to be a significant
      covariate in the correlation between D and RHC PASP.

PMID- 24028339
TI  - Borate as a synergistic anion for Marinobacter algicola ferric binding protein,
      FbpA: a role for boron in iron transport in marine life.
AB  - Boron in the ocean is generally considered a nonbiological element due to its
      relatively high concentration (0.4 mM) and depth independent concentration
      profile. Here we report an unexpected role for boron in the iron transport system
      of the marine bacterium Marinobacter algicola. Proteome analysis under varying
      boron concentrations revealed that the periplasmic ferric binding protein (Mb
      FbpA) was among the proteins whose expression was most affected, strongly
      implicating the involvement of boron in iron utilization. Here we show that boron
      facilitates Fe(3+) sequestration by Mb-FbpA at pH 8 (oceanic pH) by acting as a
      synergistic anion (B(OH)4(1-)). Fe(3+) sequestration does not occur at pH 6.5
      where boric acid (B(OH)3; pK(a) = 8.55) is the predominant species. Borate anion
      is also shown to bind to apo-Mb-FbpA with mM affinity at pH 8, consistent with
      the biological relevance implied from boron's oceanic concentration (0.4 mM).
      Borate is among those synergistic anions tested which support the strongest
      Fe(3+) binding to Mb-FbpA, where the range of anion dependent affinity constants
      is log K'(eff) = 21-22. Since the pKa of boric acid (8.55) lies near the pH of
      ocean water, changes in oceanic pH, as a consequence of fluctuations in
      atmospheric CO2, may perturb iron uptake in many marine heterotrophic bacteria
      due to a decrease in oceanic borate anion concentration.

PMID- 24028341
TI  - Folate receptor alpha associated with triple-negative breast cancer and poor
      prognosis.
AB  - CONTEXT: Folate receptor alpha (FRA) has been shown to be selectively expressed
      in several types of human cancer, including breast cancer. Currently, several FRA
      target therapies are under intensive study. OBJECTIVE: To investigate the
      expression pattern of FRA in a large cohort of patients with breast cancer and
      analyze its relationship with different clinicopathologic features, with
      expression of several key biomarkers, and with clinical outcome. DESIGN: Four
      hundred forty-seven cases of infiltrating ductal carcinoma diagnosed between 1997
      and 2008 at the University of Rochester Medical Center were identified and
      reviewed, and 25 blocks of tissue microassays were constructed. The association
      between expression of FRA and clinicopathologic features; expression of estrogen
      receptor (ER), progesterone receptor (PR), HER2/neu, and Ki-67; and clinical
      outcome of these tumors were evaluated. RESULTS: The expression of FRA was
      significantly associated with tumors with high histologic grade, higher nodal
      stages, ER/PR negativity, and high proliferative activity (Ki-67 >= 15%), and was
      independent of HER2/neu overexpression. In all, 74% of ER/PR-negative and 80% of
      triple-negative breast cancers expressed FRA. The expression of FRA was
      significantly associated with a worse disease-free survival. CONCLUSIONS: Our
      data demonstrate that a significant subgroup of ER/PR-negative and triple
      negative breast cancers express FRA, and its expression is associated with worse
      clinical outcome.

PMID- 24028343
TI  - Nanocrystals: why do silver and gold N-heterocyclic carbene precursors behave
      differently?
AB  - Synthesizing stable Au and Ag nanocrystals of narrow size distribution from metal
      N-heterocyclic carbene (NHC) complexes remains a challenge, particularly in the
      case of Ag and when NHC ligands with no surfactant-like properties are used. The
      formation of nanocrystals by one-phase reduction of metal-NHCs (metal = Au, Ag)
      bearing common NHC ligands, namely 1,3-diethylbenzimidazol-2-ylidene (L(1)), 1,3
      bis(mesityl)imidazol-2-ylidene (L(2)), and 1,3-bis(2,6-(i)Pr2C6H3)imidazol-2
      ylidene (L(3)), is presented herein. We show that both Au and Ag nanocrystals
      displaying narrow size distribution can be formed by reduction with amine
      boranes. The efficiency of the process and the average size and size distribution
      of the nanocrystals markedly depend on the nature of the metal and NHC ligand, on
      the sequence in the reactant addition (i.e., presence or absence of thiol during
      the reduction step), and on the presence or absence of oxygen. Dodecanethiol was
      introduced to produce stable nanocrystals associated with narrow size
      distributions. A specific reaction is observed with Ag-NHCs in the presence of
      thiols whereas Au-NHCs remain unchanged. Therefore, different organometallic
      species are involved in the reduction step to produce the seeds. This can be
      correlated to the lack of effect of NHCs on Ag nanocrystal size. In contrast,
      alteration of Au nanocrystal average size can be achieved with a NHC ligand of
      great steric bulk (L(3)). This demonstrates that a well-defined route for a given
      metal cannot be extended to another metal. 

PMID- 24028342
TI  - Biogeographic variation in the baboon: dissecting the cline.
AB  - All species demonstrate intraspecific anatomical variation. While generalisations
      such as Bergman's and Allen's rules have attempted to explain the geographic
      structuring of variation with some success, recent work has demonstrated limited
      support for these in certain Old World monkeys. This study extends this research
      to the baboon: a species that is widely distributed across sub-Saharan Africa and
      exhibits clinal variation across an environmentally disparate range. This study
      uses trend surface analysis to map the pattern of skull variation in size and
      shape in order to visualise the main axes of morphological variation. Patterns of
      shape and size-controlled shape are compared to highlight morphological variation
      that is underpinned by allometry alone. Partial regression is used to dissociate
      the effects of environmental terms, such as rainfall, temperature and spatial
      position. The diminutive Kinda baboon is outlying in size, so analyses were
      carried out with and without this taxon. Skull size variation demonstrates an
      east-west pattern, with small animals at the two extremes and large animals in
      Central and Southern Africa. Shape variation demonstrates the same geographical
      pattern as skull size, with small-sized animals exhibiting classic paedomorphic
      morphology. However, an additional north-south axis of variation emerges. After
      controlling for skull size, the diminutive Kinda baboon is no longer an outlier
      for size and shape. Also, the east-west component is no longer evident and
      discriminant function analysis shows an increased misclassification of adjacent
      taxa previously differentiated by size. This demonstrates the east-west component
      of shape variation is underpinned by skull size, while the north-south axis is
      not. The latter axis is explicable in phylogenetic terms: baboons arose in
      Southern Africa and colonised East and West Africa to the north, diverging in the
      process, aided by climate-mediated isolating mechanisms. Environmental terms
      appear poorly correlated with shape variation compared with geography. This might
      indicate that there is no simple environment-morphology association, but
      certainly demonstrates that phylogenetic history is an overbearing factor in
      baboon morphological variation. 

PMID- 24028344
TI  - Challenges in the characterization of plasma-processed three-dimensional
      polymeric scaffolds for biomedical applications.
AB  - Low-temperature plasmas offer a versatile method for delivering tailored
      functionality to a range of materials. Despite the vast array of choices offered
      by plasma processing techniques, there remain a significant number of hurdles
      that must be overcome to allow this methodology to realize its full potential in
      the area of biocompatible materials. Challenges include issues associated with
      analytical characterization, material structure, plasma processing, and uniform
      composition following treatment. Specific examples and solutions are presented
      utilizing results from analyses of three-dimensional (3D) poly(epsilon
      caprolactone) scaffolds treated with different plasma surface modification
      strategies that illustrate these challenges well. Notably, many of these
      strategies result in 3D scaffolds that are extremely hydrophilic and that enhance
      human Saos-2 osteoblast cell growth and proliferation, which are promising
      results for applications including tissue engineering and advanced biomedical
      devices. 

PMID- 24028345
TI  - Modular tagging of amplicons using a single PCR for high-throughput sequencing.
AB  - High-throughput sequencing (HTS) of PCR amplicons is becoming the method of
      choice to sequence one or several targeted loci for phylogenetic and DNA
      barcoding studies. Although the development of HTS has allowed rapid generation
      of massive amounts of DNA sequence data, preparing amplicons for HTS remains a
      rate-limiting step. For example, HTS platforms require platform-specific adapter
      sequences to be present at the 5' and 3' end of the DNA fragment to be sequenced.
      In addition, short multiplex identifier (MID) tags are typically added to allow
      multiple samples to be pooled in a single HTS run. Existing methods to
      incorporate HTS adapters and MID tags into PCR amplicons are either inefficient,
      requiring multiple enzymatic reactions and clean-up steps, or costly when applied
      to multiple samples or loci (fusion primers). We describe a method to amplify a
      target locus and add HTS adapters and MID tags via a linker sequence using a
      single PCR. We demonstrate our approach by generating reference sequence data for
      two mitochondrial loci (COI and 16S) for a diverse suite of insect taxa. Our
      approach provides a flexible, cost-effective and efficient method to prepare
      amplicons for HTS. 

PMID- 24028346
TI  - Structural changes in the bronchial mucosa of young children at risk of
      developing asthma.
AB  - BACKGROUND: Bronchial asthma often starts in early childhood. Clinical
      manifestation of the disease is likely due to inflammatory processes in the
      airways initiated by various stimuli. Developed remodelling is regularly observed
      in the bronchial mucosa of adult asthmatics but we still lack information about
      its onset and latter development with the natural course of the disease. In this
      study, we analysed histological findings in bronchial biopsies obtained from very
      young children (under 4 yr of age). We hypothesized that initial undetectable
      changes in the airway epithelium of children predisposed to asthma may be one of
      the first mechanisms leading to morphological changes in the bronchial mucosa.
      METHODS: We measured the thickness of the basement membrane using a light
      microscope and analysed the presence of its three basic structural glycoproteins:
      laminin, tenascin and collagen IV, using immunohistochemical techniques. We
      compared these findings in children predisposed to asthma according to the
      selected clinical criteria of the Asthma Predictive Index and in a control group
      of children. RESULTS: We found a significant difference in the thickness of the
      basement membrane between the two groups. We also found a difference in the
      subepithelial deposition of laminin and collagen IV in the basement membrane but
      no difference in the deposition of tenascin. CONCLUSIONS: We conclude that
      initial changes leading to further remodelling may start at a very early age even
      before clinical manifestation of the disease.

PMID- 24028347
TI  - 2012 Baldwin Award winner.

PMID- 24028348
TI  - Nurse-patient communication in primary care diabetes management: an exploratory
      study.
AB  - BACKGROUND: Diabetes is a major health issue for individuals and for health
      services. There is a considerable literature on the management of diabetes and
      also on communication in primary care consultations. However, few studies combine
      these two topics and specifically in relation to nurse communication. This paper
      describes the nature of nurse-patient communication in diabetes management.
      METHODS: Thirty-five primary health care consultations involving 18 patients and
      10 nurses were video-recorded as part of a larger multi-site study tracking
      health care interactions between health professionals and patients who were newly
      diagnosed with Type 2 diabetes. Patients and nurses were interviewed separately
      at the end of the 6-month study period and asked to describe their experience of
      managing diabetes. The analysis used ethnography and interaction analysis.In
      addition to analysis of the recorded consultations and interviews, the number of
      consultations for each patient and total time spent with nurses and other health
      professionals were quantified and compared. RESULTS: This study showed that
      initial consultations with nurses often incorporated completion of extensive
      checklists, physical examination, referral to other health professionals and
      distribution of written material, and were typically longer than consultations
      with other health professionals. The consultations were driven more by the
      nurses' clinical agenda than by what the patient already knew or wanted to know.
      Interactional analysis showed that protocols and checklists both help and hinder
      the communication process. This contradictory outcome was also evident at a
      health systems level: although organisational targets may have been met, the
      patient did not always feel that their priorities were attended to. Both nurses
      and patients reported a sense of being overwhelmed arising from the sheer volume
      of information exchanged along with a mismatch in expectations. CONCLUSIONS:
      Conscientious nursing work was evident but at times misdirected in terms of
      optimal use of time. The misalignment of patient expectations and clinical
      protocols highlights a common dilemma in clinical practice and raises questions
      about the best ways to balance the needs of individuals with the needs of a
      health system. Video- recording can be a powerful tool for reflection and peer
      review.

PMID- 24028349
TI  - High resolution melting analysis: rapid and precise characterisation of
      recombinant influenza A genomes.
AB  - BACKGROUND: High resolution melting analysis (HRM) is a rapid and cost-effective
      technique for the characterisation of PCR amplicons. Because the reverse genetics
      of segmented influenza A viruses allows the generation of numerous influenza A
      virus reassortants within a short time, methods for the rapid selection of the
      correct recombinants are very useful. METHODS: PCR primer pairs covering the
      single nucleotide polymorphism (SNP) positions of two different influenza A H5N1
      strains were designed. Reassortants of the two different H5N1 isolates were used
      as a model to prove the suitability of HRM for the selection of the correct
      recombinants. Furthermore, two different cycler instruments were compared.
      RESULTS: Both cycler instruments generated comparable average melting peaks,
      which allowed the easy identification and selection of the correct cloned
      segments or reassorted viruses. CONCLUSIONS: HRM is a highly suitable method for
      the rapid and precise characterisation of cloned influenza A genomes.

PMID- 24028350
TI  - Serial viscoelastic and traditional coagulation testing in horses with
      gastrointestinal disease.
AB  - OBJECTIVE: Objectives of this study were to compare the ability of serial
      thromboelastography, Sonoclot, and traditional coagulation panels to detect
      coagulopathies associated with disease category, systemic inflammatory response
      syndrome (SIRS), complications, and nonsurvival in horses with gastrointestinal
      disease. DESIGN: Prospective clinical evaluation. SETTING: University referral
      hospital. ANIMALS: One hundred twenty-one horses admitted as emergencies for
      gastrointestinal disease and 28 healthy adult horses. INTERVENTION: Blood samples
      were collected <=4 times from emergency horses (admission and if surviving and
      hospitalized on days 2-4) and once from healthy horses. Thromboelastography (with
      and without tissue factor activation), Sonoclot, and a traditional coagulation
      panel were performed on each sample. MEASUREMENTS AND MAIN RESULTS: Emergency
      horses were grouped based on disease category (ie, nonstrangulating medical,
      nonstrangulating surgical, strangulating, and inflammatory), survival to
      discharge, SIRS at admission, requirement for exploratory celiotomy, ileus,
      diarrhea, fever, thrombophlebitis, and laminitis. Changes over time were
      evaluated individually and compared between disease groups. Horses with
      gastrointestinal disease had dynamic changes in coagulation and fibrinolysis
      during the first 4 days of hospitalization that were correlated with disease
      category, SIRS, complications, and fatality. The multivariate logistic regression
      model for nonsurvival included activated partial thromboplastin time on day 2 and
      LY30 on day 3 (overall model significance P < 0.0001). The odds of nonsurvival
      were 23.75 times higher if activated partial thromboplastin time was >85.6 s on
      day 2 and 9.38 times higher if LY30 was >1% on day 3. CONCLUSIONS: Horses with
      gastrointestinal disease have activation of coagulation and fibrinolysis.
      Magnitude of change in these parameters is small and predictive value moderate,
      making application of these tests to direct therapy in clinical patients
      difficult. Effect of specific treatments (eg, surgery) on these tests and
      coagulation has not been determined. Further studies are required to determine if
      these tests could be used to help monitor response to treatment in individual
      animals or specific disease states.

PMID- 24028351
TI  - Life on hold: the experience of living with neuromyelitis optica.
AB  - PURPOSE: Neuromyelitis optica (NMO) is a rare autoimmune condition characterised
      by acute relapses of optic neuritis and extensive transverse myelitis. The aim of
      this qualitative study was to develop an improved understanding of the
      experiences of people living with NMO. METHOD: Fifteen participants completed a
      semi-structured interview and data were interpreted using a constant comparative
      method. Participants were recruited from the Northern UK NMO Service. RESULTS:
      Five major themes were identified: diagnosis and treatment, symptoms, adjustment,
      identity and support. CONCLUSION: Results suggest NMO is a difficult condition to
      live with due to the unpredictability of relapses and accrued disability of
      visual or spinal symptoms occurring with each relapse. Poor vision, reduced
      mobility, bladder dysfunction and pain affected participants' independence and
      experience of living with NMO. Participants reported that during relapse and
      recovery they would "put their life on hold". They identified the importance of
      periods of stability to enable them to adjust to their condition and therefore
      aim for "normality" of life that they believed was comparable to their peers.
      Implications for Rehabilitation Disability due to NMO has a major impact on an
      individual's life, abilities and identity. Timely treatment of relapse is
      essential to reduce or prevent disability. Health care professionals need to
      coordinate care locally and nationally. Multi-disciplinary work is vital to
      promote adjustment, coping strategies and support for people living with NMO.

PMID- 24028352
TI  - An experimental study of the regulation of glycolytic oscillations in yeast.
AB  - We have studied oscillating glycolysis in the strain BY4743 and isogenic strains
      with deletions of genes encoding enzymes in glycolysis, mitochondrial electron
      transport and ATP synthesis. We found that deletion of the gene encoding the
      hexokinase 1 isoform does not affect the oscillations while deletion of the gene
      encoding the hexokinase 2 isoform results in oscillations with smaller amplitude.
      The latter is associated with an almost 50% decrease in hexokinase activity.
      Deletions in the genes encoding the alpha- and beta-subunits of
      phosphofructokinase abolish the oscillations entirely. This loss in oscillatory
      activity is associated with a fourfold decrease in phosphofructokinase activity.
      Deletions of genes encoding subunits of the F1F0 ATPase also inhibit the
      oscillations in accordance with earlier studies using for example inhibitors.
      Finally, we identified an apparently new control point involving the
      mitochondrial cytochrome c oxidase. The latter is difficult to explain as
      oscillatory activity entails 100% inhibition of this enzyme. The mitochondria of
      this strain seem to have normal F1F0 ATPase activity. Overall these results
      support earlier experimental and model studies suggesting that in addition to
      processes within glycolysis also processes outside this pathway contribute to the
      control of the oscillatory behaviour.

PMID- 24028353
TI  - Treatment of BK virus-associated hemorrhagic cystitis in pediatric hematopoietic
      stem cell transplant recipients with cidofovir: a single-center experience.
AB  - BACKGROUND: BK virus (BKV)-associated hemorrhagic cystitis (BKV-HC) is a severe
      complication after hematopoietic stem cell transplantation (HSCT). Cidofovir
      (CDV) has emerged as an effective agent for the treatment of BKV nephropathy, but
      its use for BKV-HC in pediatric HSCT recipients has not yet been established as a
      standard therapy. PATIENT AND METHODS: We retrospectively investigated the
      efficacy and safety of CDV therapy for patients with BKV-HC at a single
      institution and analyzed the clinical management outcomes. RESULTS: From April
      2009 to July 2011, 12 patients developed BKV-HC at a median of 37 days after
      transplant (range 15-59 days). The cumulative incidence was 9% and the median
      peak of the urine BKV load was 2.5 * 10(10) copies/mL (range 1.4 * 10(9) -1.2 *
      10(11) copies/mL). Eleven patients received intravenous CDV (5 mg/kg/dose, with
      probenecid), whereas 1 patient received CDV (5 mg/kg/dose, without probenecid)
      intravesically. The median duration of therapy was 25 days (range 9-73 days), and
      a median of 2 doses was given (range 1-4). A reduction of >= 1 log in the BKV
      load was found in 11 patients, while 1 patient did not have any significant
      change in BKV load. Clinical improvement was observed in all cases, and no HC
      related death was observed. CDV-related toxicity occurred in 1 patient (8%) and
      spontaneously resolved. CONCLUSIONS: CDV appears to be an effective and safe
      treatment for BKV-HC in pediatric HSCT recipients, but prospective trials are
      warranted to support its use.

PMID- 24028354
TI  - Effects of medication reviews performed by a physician on treatment with fracture
      preventing and fall-risk-increasing drugs in older adults with hip fracture-a
      randomized controlled study.
AB  - OBJECTIVES: To investigate whether medication reviews increase treatment with
      fracture-preventing drugs and decrease treatment with fall-risk-increasing drugs.
      DESIGN: Randomized controlled trial (1:1). SETTING: Departments of orthopedics,
      geriatrics, and medicine at Sahlgrenska University Hospital, Gothenburg, Sweden.
      PARTICIPANTS: One hundred ninety-nine consecutive individuals with hip fracture
      aged 65 and older. INTERVENTION: Medication reviews, based on assessments of
      risks of falls and fractures, regarding fracture-preventing and fall-risk
      increasing drugs, performed by a physician, conveyed orally and in written form
      to hospital physicians during the hospital stay, and to general practitioners
      after discharge. MEASUREMENTS: Primary outcomes were changes in treatment with
      fracture-preventing and fall-risk-increasing drugs 12 months after discharge.
      Secondary outcomes were falls, fractures, deaths, and physicians' attitudes
      toward the intervention. RESULTS: At admission, 26% of intervention and 29% of
      control participants were taking fracture-preventing drugs, and 12% and 11%,
      respectively, were taking bone-active drugs, predominantly bisphosphonates. After
      12 months, 77% of intervention and 58% of control participants were taking
      fracture-preventing drugs (P = .01), and 29% and 15%, respectively, were taking
      bone-active drugs (P = .04). Mean number of fall-risk-increasing drugs per
      participants was 3.1 (intervention) and 3.1 (control) at admission and 2.9
      (intervention) and 3.1 (control) at 12 months (P = .62). No significant
      differences in hard endpoints were found. The responding physicians (n = 65)
      appreciated the intervention; on a scale from 1 (very bad) to 6 (very good), the
      median rating was 5 (interquartile range (IQR) 4-6) for the oral part and 5 (IQR
      4-5.5) for the text part. CONCLUSION: Medication reviews performed and conveyed
      by a physician increased treatment with fracture-preventing drugs but did not
      significantly decrease treatment with fall-risk-increasing drugs in older adults
      with hip fracture. Prescribing physicians appreciated this intervention.

PMID- 24028355
TI  - Midlife hypertensive status and cognitive function 20 years later: the Southall
      and Brent revisited study.
AB  - OBJECTIVES: To investigate long-term prospective associations between a range of
      measurements of hypertensive status in midlife and cognitive impairment 20 years
      later. DESIGN: Cohort study. SETTING: Two areas (Southall and Brent) of northwest
      London. PARTICIPANTS: Survey samples of a multiethnic population (European,
      African Caribbean, South Asian) aged 40 to 67 were followed up 20 years later.
      MEASUREMENTS: Comprehensive cardiovascular assessments were performed at
      baseline, including measurements of resting blood pressure (BP) and, in a
      subsample, ambulatory BP. At follow-up, a battery of cognitive assessments was
      administered, and a composite outcome was derived, with impairment defined as the
      lowest 10% within each ethnic group. Logistic regression models were used to
      investigate associations with prior measures of hypertensive status. RESULTS: In
      1,484 participants at follow-up, cognitive impairment showed significant U-shaped
      associations with baseline diastolic BP (DBP) and mean arterial pressure (MAP;
      strongest for those aged >= 50 at baseline), independent of a range of
      covariates, but no associations were found with systolic BP or pulse pressure.
      Cognitive impairment was also associated with antihypertensive medication use and
      higher evening ambulatory DBP at baseline. No substantial differences in
      strengths of association were found between ethnic groups. CONCLUSION: Low and
      high DBP and MAP were associated with cognitive impairment 20 years later. Higher
      evening DBP on ambulatory monitoring was also associated with greater risk.

PMID- 24028356
TI  - People's attitudes, beliefs, and experiences regarding polypharmacy and
      willingness to Deprescribe.
AB  - OBJECTIVES: To capture people's attitudes, beliefs, and experiences regarding the
      number of medications they are taking and their feelings about stopping
      medications. DESIGN: Administration of a validated questionnaire. SETTING:
      Multidisciplinary ambulatory consulting service at the Royal Adelaide Hospital.
      PARTICIPANTS: Participants were individuals aged 18 and older (median 71.5)
      taking at least one regular prescription medication; 100 participants completed
      all items of the questionnaire, 65 of whom were aged 65 and older. MEASUREMENTS:
      Participants were administered the 15-item Patients' Attitudes Towards
      Deprescribing (PATD) questionnaire. RESULTS: Participants were taking an average
      of 10 different prescription and nonprescription (including complementary),
      regular and as-needed medications. More than 60% felt that they were taking a
      "large number" of medications, and 92% stated that they would be willing to stop
      one or more of their current medications if possible. Number of regular
      medications, age, and number of medical conditions were not found to be
      correlated with willingness to stop a medication. The findings were similar in
      older and younger participants. CONCLUSION: This study has shown that a cohort of
      mostly older adults were largely accepting of a trial of cessation of
      medication(s) that their prescriber deemed to be no longer required. Because few
      factors were associated with willingness to cease medications, all patients
      should be individually evaluated for deprescribing.

PMID- 24028357
TI  - Operationalization of frailty using eight commonly used scales and comparison of
      their ability to predict all-cause mortality.
AB  - OBJECTIVES: To operationalize frailty using eight scales and to compare their
      content validity, feasibility, prevalence estimates of frailty, and ability to
      predict all-cause mortality. DESIGN: Secondary analysis of the Survey of Health,
      Ageing and Retirement in Europe (SHARE). SETTING: Eleven European countries.
      PARTICIPANTS: Individuals aged 50 to 104 (mean age 65.3 +/- 10.5, 54.8% female, N
      = 27,527). MEASUREMENTS: Frailty was operationalized using SHARE data based on
      the Groningen Frailty Indicator, the Tilburg Frailty Indicator, a 70-item Frailty
      Index (FI), a 44-item FI based on a Comprehensive Geriatric Assessment (FI-CGA),
      the Clinical Frailty Scale, frailty phenotype (weighted and unweighted versions),
      the Edmonton Frail Scale, and the FRAIL scale. RESULTS: All scales had fewer than
      6% of cases with at least one missing item, except the SHARE-frailty phenotype
      (11.1%) and the SHARE-Tilburg (12.2%). In the SHARE-Groningen, SHARE-Tilburg,
      SHARE-frailty phenotype, and SHARE-FRAIL scales, death rates were 3 to 5 times as
      high in excluded cases as in included ones. Frailty prevalence estimates ranged
      from 6% (SHARE-FRAIL) to 44% (SHARE-Groningen). All scales categorized 2.4% of
      participants as frail. Of unweighted scales, the SHARE-FI and SHARE-Edmonton
      scales most accurately predicted mortality at 2 (SHARE-FI area under the receiver
      operating characteristic curve (AUC) = 0.77, 95% confidence interval (CI) = 0.75
      0.79); SHARE-Edmonton AUC = 0.76, 95% CI = 0.74-0.79) and 5 (both AUC = 0.75, 95%
      CI = 0.74-0.77) years. The continuous score of the weighted SHARE-frailty
      phenotype (AUC = 0.77, 95% CI = 0.75-0.78) predicted 5-year mortality better than
      the unweighted SHARE-frailty phenotype (AUC = 0.70, 95% CI = 0.68-0.71), but the
      categorical score of the weighted SHARE-frailty phenotype did not (AUC = 0.70,
      95% CI = 0.68-0.72). CONCLUSION: Substantive differences exist between scales in
      their content validity, feasibility, and ability to predict all-cause mortality.
      These frailty scales capture related but distinct groups. Weighting items in
      frailty scales can improve their predictive ability, but the trade-off between
      specificity, predictive power, and generalizability requires additional
      evaluation.

PMID- 24028358
TI  - Multidimensional team-based intervention using musical cues to reduce odds of
      facility-acquired pressure ulcers in long-term care: a paired randomized
      intervention study.
AB  - OBJECTIVES: To test the effectiveness of a pressure ulcer (PU) prevention
      intervention featuring musical cues to remind all long-term care (LTC) staff
      (nursing and ancillary) to help every resident move or reposition every 2 hours.
      DESIGN: Twelve-month paired-facility two-arm (with one-arm crossover) randomized
      intervention trial. SETTING: Ten midwestern U.S. LTC facilities. Four treatment
      facilities received intervention during Months 1 to 12, four comparison
      facilities received intervention during Months 7 to 12, and two pseudo-control
      facilities received no intervention. PARTICIPANTS: LTC facility residents (N =
      1,928). INTERVENTION: All facility staff received in-person education, video, and
      handouts, and visiting family members received informational pamphlets on PU
      prevention and an intervention featuring musical cues. Nurse-led
      multidisciplinary staff teams presented the cues as prompts for staff and family
      to reposition residents or remind them to move. Musical selections (with and
      without lyrics) customized to facility preferences were played daily over the
      facility intercom or public address system every 2 hours for the 12-hour daytime
      period. MEASUREMENTS: Primary outcome measure was the frequency of new facility
      acquired PUs divided by the total number of facility Minimum Data Set (MDS)
      resident assessments conducted during the study period. RESULTS: Odds of a new PU
      were lower in intervention facilities (P = .08) for MDS 2.0 assessments and were
      significantly lower (P = .05) for MDS 3.0. Mean odds ratios suggested
      intervention facility residents were 45% less likely than comparison facility
      residents to develop a new PU. CONCLUSION: Customized musical cues that prompt
      multidisciplinary staff teams to encourage or enable movement of all residents
      hold promise for reducing facility-acquired PUs in LTC settings.

PMID- 24028359
TI  - Effects of care management and telehealth: a longitudinal analysis using medicare
      data.
AB  - OBJECTIVES: To evaluate mortality and healthcare utilization effects of an
      intervention that combined care management and telehealth, targeting individuals
      with congestive heart failure, chronic obstructive pulmonary disease, or diabetes
      mellitus. DESIGN: Retrospective matched cohort study. SETTING: Northwest United
      States. PARTICIPANTS: High-cost Medicare fee-for-service beneficiaries (N =
      1,767) enrolled in two Centers for Medicare and Medicaid Services demonstration
      participating clinics and a propensity-score matched control group. INTERVENTION:
      The Health Buddy Program, which integrates a content-driven telehealth system
      with care management. MEASUREMENTS: Mortality, inpatient admissions, hospital
      days, and emergency department (ED) visits during the 2-year study period were
      measured. Cox-proportional hazard models and negative binomial regression models
      were used to assess the relationship between the intervention and survival and
      utilization, controlling for demographic and health characteristics that were
      statistically different between groups after matching. RESULTS: At 2 years,
      participants offered the Health Buddy Program had 15% lower risk-adjusted all
      cause mortality (hazard ratio (HR) = 0.85, 95% confidence interval (CI) = 0.74
      0.98; P = .03) and had reductions in the number of quarterly inpatient admissions
      from baseline to the study period that were 18% greater than those of matched
      controls during this same time period (-0.035 vs -0.003; difference-in
      differences = -0.032, 95% CI = -0.054 to -0.010, P = .005). No relationship was
      found between the Health Buddy Program and ED use or number of hospital days for
      participants who were hospitalized. The Health Buddy Program was most strongly
      associated with fewer admissions for individuals with chronic obstructive
      pulmonary disease and mortality for those with congestive heart failure.
      CONCLUSION: Care management coupled with content-driven telehealth technology has
      potential to improve health outcomes in high-cost Medicare beneficiaries.

PMID- 24028361
TI  - Implementation of an emergency department observation unit for elderly adults in
      a university-affiliated hospital in Spain: a 6-year analysis of data.

PMID- 24028360
TI  - Cognitive function and oral health-related quality of life in older adults.
AB  - OBJECTIVES: To examine the relationship between cognitive function and self
      reported oral health-related quality of life (HRQoL) in community-dwelling older
      adults. DESIGN: Cross-sectional. SETTING: Community in West Virginia.
      PARTICIPANTS: Two hundred twenty-six community-dwelling older adults.
      MEASUREMENTS: Oral HRQoL was measured using the Geriatric Oral Health Assessment
      Index (GOHAI) (range 12-60), and cognitive function was assessed using a
      comprehensive neuropsychological test battery. Dental professionals performed
      oral health examinations. RESULTS: Participants with normal cognitive function
      had higher GOHAI total scores (mean 55.1), indicating better oral HRQoL, than
      participants with cognitive impairment without dementia (CIND) (mean 52.3) and
      mild dementia (mean 51.0). The difference remained significant after controlling
      for sociodemographic, health status, comorbidity, and clinical dental status
      covariates. CONCLUSION: Oral HRQoL, as measured using the GOHAI, was better in
      participants with normal cognitive function than in those with CIND of mild
      dementia in the population studied.

PMID- 24028362
TI  - Drug prescription suitability: application of the Screening Tool of Older
      Persons' Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START)
      criteria in a day-care geriatric hospital.

PMID- 24028363
TI  - Pharmacist-initiated management of antagonistic interactions between
      anticholinergic drugs and acetyl cholinesterase inhibitors in individuals with
      dementia.

PMID- 24028364
TI  - Validation of a frailty index from the older persons and informal caregivers
      survey minimum data set.

PMID- 24028365
TI  - Hearing loss and depression in older adults.

PMID- 24028366
TI  - Preventing trip-related falls by community-dwelling adults: a prospective study.

PMID- 24028367
TI  - Prediction of asthma exacerbations in elderly adults: results of a 1-year
      prospective study.

PMID- 24028368
TI  - Ability of fracture risk assessment tool and national osteoporosis guideline
      group guidance to stratify people appropriately before fracture.

PMID- 24028369
TI  - Elderly-onset systemic lupus erythematosus.

PMID- 24028370
TI  - Gabapentin withdrawal: case report in an older adult and review of the
      literature.

PMID- 24028371
TI  - Severe hypoglycemia associated with levofloxacin in a healthy older woman.

PMID- 24028372
TI  - Researcher becomes first responder to older driver crash.

PMID- 24028373
TI  - Re-evaluating psychotropic drug use across care settings.

PMID- 24028374
TI  - A geripill for successful aging.

PMID- 24028375
TI  - Aggrecan- and COMP-loaded poly-(lactic-co-glycolic acid) nanoparticles stimulate
      chondrogenic differentiation of human mesenchymal stem cells.
AB  - During embryogenesis, specific proteins expressed in cells have key roles in the
      formation of differentiated cells and tissues. Delivery of specific proteins into
      specific cells, both in vitro and in vivo, has proved to be exceedingly
      difficult. In this study, we developed a safe and efficient protein delivery
      system using encapsulation of proteins into biodegradable poly-(lactic-co
      glycolic acid) (PLGA) nanoparticles (NPs). The PLGA NPs were used to deliver
      proteins into human mesenchymal stem cells (hMSCs). Fluorescent markers loaded
      into the PLGA NPs were used to verify the internalization of NPs into hMSCs using
      FACS analysis and confocal microscopy. With these methods, we demonstrated that
      the encapsulated model proteins are readily delivered into hMSCs, released from
      the NP vehicles, and, finally, moved into the cytosols. Using chondrogenesis
      related proteins such as aggrecan and cartilage oligomeric matrix protein (COMP),
      chondrogenic differentiation of hMSCs treated with aggrecan and COMP encapsulated
      PLGA NPs was clearly observed and caused to differentiate into chondrocytes. 

PMID- 24028376
TI  - Bibliometrics of systematic reviews: analysis of citation rates and journal
      impact factors.
AB  - BACKGROUND: Systematic reviews are important for informing clinical practice and
      health policy. The aim of this study was to examine the bibliometrics of
      systematic reviews and to determine the amount of variance in citations predicted
      by the journal impact factor (JIF) alone and combined with several other
      characteristics. METHODS: We conducted a bibliometric analysis of 1,261
      systematic reviews published in 2008 and the citations to them in the Scopus
      database from 2008 to June 2012. Potential predictors of the citation impact of
      the reviews were examined using descriptive, univariate and multiple regression
      analysis. RESULTS: The mean number of citations per review over four years was
      26.5 (SD +/- 29.9) or 6.6 citations per review per year. The mean JIF of the
      journals in which the reviews were published was 4.3 (SD +/- 4.2). We found that
      17% of the reviews accounted for 50% of the total citations and 1.6% of the
      reviews were not cited. The number of authors was correlated with the number of
      citations (r = 0.215, P < 0.001). Higher numbers of citations were associated
      with the following characteristics: first author from the United States (36.5
      citations), an ICD-10 chapter heading of Neoplasms (31.8 citations), type of
      intervention classified as Investigation, Diagnostics or Screening (34.7
      citations) and having an international collaboration (32.1 citations). The JIF
      alone explained more than half of the variation in citations (R(2) = 0.59) in
      univariate analysis. Adjusting for both JIF and type of intervention increased
      the R2 value to 0.81. Fourteen percent of reviews published in the top quartile
      of JIFs (>= 5.16) received citations in the bottom quartile (eight or fewer),
      whereas 9% of reviews published in the lowest JIF quartile (<= 2.06) received
      citations in the top quartile (34 or more). Six percent of reviews in journals
      with no JIF were also in the first quartile of citations. CONCLUSIONS: The JIF
      predicted over half of the variation in citations to the systematic reviews.
      However, the distribution of citations was markedly skewed. Some reviews in
      journals with low JIFs were well-cited and others in higher JIF journals received
      relatively few citations; hence the JIF did not accurately represent the number
      of citations to individual systematic reviews.

PMID- 24028377
TI  - A preliminary assessment of financial stability, efficiency, health systems and
      health outcomes using performance-based contracts in Belize.
AB  - Over the last 10 years, Belize has implemented a National Health Insurance (NHI)
      program that uses performance-based contracts with both public and private
      facilities to improve financial sustainability, efficiency and service provision.
      Data were collected at the facility, district and national levels in order to
      assess trends in financial sustainability, efficiency payments, year-end bonuses
      and health system and health outcomes. A difference-in-difference approach was
      used to assess the difference in technical efficiency between private and public
      facilities. The results show that per capita spending on services provided by the
      NHI program has decreased over the period 2006-2009 from BZ$177 to BZ$136. The
      private sector has achieved higher levels of technical efficiency, but lower
      percentages of efficiency and year-end bonus payments. Districts with contracts
      through the NHI program showed greater improvements in facility births, nurse
      density, reducing maternal mortality, diabetes deaths and morbidity from
      bronchitis, emphysema and asthma than districts without contracts over the period
      2006-2010. This preliminary assessment of Belize's pay-for-performance system
      provides some positive results, however further research is needed to use the
      lessons learned from Belize to implement similar reforms in other systems. 

PMID- 24028378
TI  - Theoretical study of M(+)-RG2 (M+ = Li, Na, Be, Mg; RG = He-Rn).
AB  - Ab initio calculations were employed to determine the geometry (MP2 level), and
      dissociation energies [MP2 and RCCSD(T) levels], of the M(IIa)(+)-RG2 species,
      where M(IIa) is a group 2 metal, Be or Mg, and RG is a rare gas (He-Rn). We
      compare the results with similar calculations on M(Ia)(+)-RG2, where M(Ia) is a
      group 1 metal, Li or Na. It is found that the complexes involving the group 1
      metals are linear (or quasilinear), whereas those involving the group 2 metals
      are bent. We discuss these results in terms of hybridization and the various
      interactions in these species. Trends in binding energies, D(e), bond lengths,
      and bond angles are discussed. We compare the energy required for the removal of
      a single RG atom from M(+)-RG2 (D(e2)) with that of the dissociation energy of
      M(+)-RG (D(e1)); some complexes have D(e2) > D(e1), some have D(e2) < D(e1), and
      some have values that are about the same. We also present relaxed angular cuts
      through a selection of potential energy surfaces. The trends observed in the
      geometries and binding energies of these complexes are discussed. Mulliken,
      natural population, and atoms-in-molecules (AIM) population analyses are
      performed, and it is concluded that the AIM method is the most reliable, giving
      results that are in line with molecular orbital diagrams and contour plots;
      unphysical amounts of charge transfer are suggested by the Mulliken and natural
      population approaches.

PMID- 24028380
TI  - Dynamic nuclear polarization NMR spectroscopy allows high-throughput
      characterization of microporous organic polymers.
AB  - Dynamic nuclear polarization (DNP) solid-state NMR was used to obtain natural
      abundance (13)C and (15)N CP MAS NMR spectra of microporous organic polymers with
      excellent signal-to-noise ratio, allowing for unprecedented details in the
      molecular structure to be determined for these complex polymer networks.
      Sensitivity enhancements larger than 10 were obtained with bis-nitroxide radical
      at 14.1 T and low temperature (~105 K). This DNP MAS NMR approach allows
      efficient, high-throughput characterization of libraries of porous polymers
      prepared by combinatorial chemistry methods. 

PMID- 24028381
TI  - Sleep credit and debit: grey matter and emotional intelligence in the balance?

PMID- 24028379
TI  - Pregnane xenobiotic receptors and membrane progestin receptors: role in
      neurosteroid-mediated motivated behaviours.
AB  - Progestogens have actions in the midbrain ventral tegmental area (VTA) to mediate
      motivated behaviours, such as those involved in reproductive processes, among
      female rodents. In the VTA, the formation and actions of one progestogen, 5alpha
      pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), are necessary and sufficient to
      facilitate sexual responding (measured by lordosis) of female rodents. Although
      3alpha,5alpha-THP can be produced after metabolism of ovarian progesterone,
      3alpha,5alpha-THP is also a neurosteroid produced de novo in brain regions, such
      as the VTA. There can be dynamic changes in 3alpha,5alpha-THP production
      associated with behavioural experience, such as mating. Questions of interest are
      the sources and targets of 3alpha,5alpha-THP. Regarding sources, the pregnane
      xenobiotic receptor (PXR) may be a novel factor involved in 3alpha,5alpha-THP
      metabolism in the VTA (as well as a direct target of 3alpha,5alpha-THP). We have
      identified PXR in the midbrain of female rats, and manipulating PXR in this
      region reduces 3alpha,5alpha-THP synthesis and alters lordosis, as well as
      affective and social behaviours. Regarding targets, recent studies have focused
      on the role of membrane progestin receptors (mPRs). We have analysed the
      expression of two of the common forms of these receptors (mPRalpha/paqr7 and
      mPRbeta/paqr8) in female rats. The expression of mPRalpha was observed in
      peripheral tissues and brain areas, including the hypothalamus and midbrain. The
      expression of mPRbeta was only observed in brain tissues and was abundant in the
      midbrain and hypothalamus. To our knowledge, studies of these receptors in
      mammalian models have been limited to expression and regulation, instead of
      function. One question that was addressed was the functional effects of
      progestogens via mPRalpha and mPRbeta in the midbrain of hormone-primed rats for
      lordosis. Studies to date suggest that mPRbeta may be an important target of
      progestogens in the VTA for lordosis. Taken together, the result of these studies
      demonstrate that PXR is involved in the production of 3alpha,5alpha-THP in the
      midbrain VTA. Moreover, mPRs may be a target for the actions of progestogens in
      the VTA for lordosis. 

PMID- 24028382
TI  - Mycobacterium tuberculosis is the causative agent of tuberculosis in the southern
      ecological zones of Cameroon, as shown by genetic analysis.
AB  - BACKGROUND: Tuberculosis (TB) is a major cause of mortality and suffering
      worldwide, with over 95% of TB deaths occurring in low- and middle-income
      countries. In recent years, molecular typing methods have been widely used in
      epidemiological studies to aid the control of TB, but this usage has not been the
      case with many African countries, including Cameroon. The aims of the present
      investigation were to identify and evaluate the diversity of the Mycobacterium
      tuberculosis complex (MTBC) isolates circulating in two ecological zones of
      Cameroon, seven years after the last studies in the West Region, and after the re
      organization of the National TB Control Program (NTBCP). These were expected to
      shed light also on the transmission of TB in the country. The study was conducted
      from February to July 2009. During this period, 169 patients with symptomatic
      disease and with sputum cultures that were positive for MTBC were randomly
      selected for the study from amongst 964 suspected patients in the savannah mosaic
      zone (West and North West regions) and the tropical rainforest zone (Central
      region). After culture and diagnosis, DNA was extracted from each of the MTBC
      isolates and transported to the BecA-ILRI Hub in Nairobi, Kenya for molecular
      analysis. METHODS: Genetic characterization was done by mycobacterial
      interspersed repetitive unit-variable number tandem repeat typing (MIRU-VNTR) and
      Spoligotyping. RESULTS: Molecular analysis showed that all TB cases reported in
      this study were caused by infections with Mycobacterium tuberculosis (98.8%) and
      Mycobacterium africanum (M. africanum) (1.2%) respectively. We did not detect any
      M. bovis. Comparative analyses using spoligotyping revealed that the majority of
      isolates belong to major clades of M. tuberculosis: Haarlem (7.6%), Latin
      American-Mediterranean (34.4%) and T clade (26.7%); the remaining isolates
      (31.3%) where distributed among the minor clades. The predominant group of
      isolates (34.4%) corresponded to spoligotype 61, previously described as the
      "Cameroon family. Further analysis based on MIRU-VNTR profiles had greater
      resolving power than spoligotyping and defined additional genotypes in the same
      spoligotype cluster. CONCLUSION: The molecular characterization of MTBC strains
      from humans in two ecological regions of Cameroon has shown that M. tuberculosis
      sensu stricto is the predominant agent of TB cases in the zones. Three decades
      ago, TB was reported to be caused by M. africanum in 56.0% of cases. The present
      findings are consistent with a major shift in the prevalence of M. tuberculosis
      in Cameroon.

PMID- 24028384
TI  - Synthesis of an S(T) = 7 [Mn3] mixed-valence complex based on 1,3-propanediol
      ligand derivatives and its one-dimensional assemblies.
AB  - Controlled organization of high-spin complexes and single-molecule magnets is a
      great challenge in molecular magnetism in order to study the effect of the
      intercomplex magnetic interactions on the intrinsic properties of a given
      magnetic object. In this work, a new S(T) = 7 trinuclear mixed-valence Mn
      complex, [Mn(III)Mn(II)2(LA)2(Br)4(CH3OH)6] .Br.(CH3OH)(1.5).(H2O)(0.5) (1), is
      reported using a pyridinium-functionalized 1,3-propanediol ligand (H2L(A)Br = 1
      (3-bromo-2,2-bis(hydroxymethyl)propyl)pyridinium bromide). Using azido anions as
      bridging ligands and different pyridinium-functionalized 1,3-propanediol ligands
      (H2L(B)Br = 1-(3-bromo-2,2-bis(hydroxymethyl)propyl)-4-picolinium bromide;
      H2L(C)Br = 1-(3-bromo-2,2-bis(hydroxymethyl)propyl)-3,5-lutidinium bromide), the
      linear [Mn(III)Mn(II)2L2X4](+) building block has been assembled into one
      dimensional coordination networks:
      [Mn(III)Mn(II)2(LA)2(Br)4(CH3OH)4(N3)].((C2H5)2O)1.25 (2infinity),
      [Mn(III)Mn(II)2(L(B))2(Br)4(C2H5OH)(CH3OH)(H2O)2(N3)].(H2O)0.25 (3infinity), and
      [Mn(III)Mn(II)2(L(C))2(Cl)(3.8)(Br)(0.2)(C2H5OH)3(CH3OH)(N3)] (4infinity). The
      syntheses, characterization, crystal structures, and magnetic properties of these
      new [Mn3]-based materials are reported.

PMID- 24028383
TI  - Plantar fascia anatomy and its relationship with Achilles tendon and paratenon.
AB  - Although the plantar fascia (PF) has been studied quite well from a biomechanical
      viewpoint, its microscopic properties have been overlooked: nothing is known
      about its content of elastic fibers, the features of the extracellular matrix or
      the extent of innervation. From a functional and clinical standpoint, the PF is
      often correlated with the triceps surae muscle, but the anatomical grounds for
      this link are not clear. The aim of this work was to focus on the PF macroscopic
      and microscopic properties and study how Achilles tendon diseases might affect
      it. Twelve feet from unembalmed human cadavers were dissected to isolate the PF.
      Specimens from each PF were tested with various histological and
      immunohistochemical stains. In a second stage, 52 magnetic resonance images (MRI)
      obtained from patients complaining of aspecific ankle or foot pain were analyzed,
      dividing the cases into two groups based on the presence or absence of signs of
      degeneration and/or inflammation of the Achilles tendon. The thickness of PF and
      paratenon was assessed in the two groups and statistical analyses were conducted.
      The PF is a tissue firmly joined to plantar muscles and skin. Analyzing its
      possible connections to the sural structures showed that this fascia is more
      closely connected to the paratenon of Achilles tendon than to the Achilles
      tendon, through the periosteum of the heel. The PF extended medially and
      laterally, continuing into the deep fasciae enveloping the abductor hallucis and
      abductor digiti minimi muscles, respectively. The PF was rich in hyaluronan,
      probably produced by fibroblastic-like cells described as 'fasciacytes'. Nerve
      endings and Pacini and Ruffini corpuscles were present, particularly in the
      medial and lateral portions, and on the surface of the muscles, suggesting a role
      for the PF in the proprioception of foot. In the radiological study, 27 of the 52
      MRI showed signs of Achilles tendon inflammation and/or degeneration, and the PF
      was 3.43 +/- 0.48 mm thick (99%CI and SD = 0.95), as opposed to 2.09 +/- 0.24 mm
      (99%CI, SD = 0.47) in the patients in which the MRI revealed no Achilles tendon
      diseases; this difference in thickness of 1.29 +/- 0.57 mm (99%CI) was
      statistically significant (P < 0.001). In the group of 27/52 patients with
      tendinopathies, the PF was more than 4.5 mm thick in 5, i.e. they exceeded the
      threshold for a diagnosis of plantar fasciitis. None of the other 25/52 paitents
      had a PF more than 4 mm thick. There was a statistically significant correlation
      between the thicknesses of the PF and the paratenon. These findings suggest that
      the plantar fascia has a role not only in supporting the longitudinal arch of the
      foot, but also in its proprioception and peripheral motor coordination. Its
      relationship with the paratenon of the Achilles tendon is consistent with the
      idea of triceps surae structures being involved in the PF pathology, so their
      rehabilitation can be considered appropriate. Finally, the high concentration of
      hyaluronan in the PF points to the feasibility of using hyaluronan injections in
      the fascia to treat plantar fasciitis. 

PMID- 24028385
TI  - Reproducibility in echocardiographic two- and three-dimensional mitral valve
      assessment.
AB  - BACKGROUND: Three-dimensional transesophageal echocardiography (3DTEE) has been
      demonstrated to provide more accurate information than two-dimensional
      transesophageal echocardiography (2DTEE) in the localization of mitral valve
      prolapse (MVP). However, most studies have been single-rater studies. Few results
      were tested for inter-observer variability with a single second rater. This
      multicenter study aimed to determine reliability of 2D and 3DTEE mitral valve
      evaluations by calculating inter-observer agreement between various
      echocardiographers. METHODS: Fifteen observers from 4 institutions in Germany and
      Switzerland interpreted 2D and 3DTEE images from 6 patients selected to represent
      a large spectrum of MVP diversity. Surgical findings served as reference.
      Individual assessments of MVP and ruptured chordae tendineae (ChR) pathology were
      compared by calculating Randolph's free-marginal multirater kappa coefficient.
      RESULTS: Accuracy of MVP evaluation with 3DTEE was 83.9%, CI [81.0%; 86.8%] and
      78.7% CI [76.6% 80.8%] with 2DTEE. Flail leaflets with chordal ruptures were
      described correctly in 91.1%, CI [85.8, 96.4] with 3D compared to 71.1%, CI
      [65.0, 77.2] with 2DTEE. The multirater kappa coefficient of inter-observer
      agreement among all 15 observers was kappa = 0.65/0.58 for 3D/2D evaluation of
      MVP and kappa = 0.70/0.54 for detection of ChR. CONCLUSION: Three-dimensional
      assessment of MVP was superior to 2DTEE, although the accuracy of both 3DTEE and
      2DTEE was found to be lower than previously published. 3D MVP assessment is less
      operator dependent than 2DTEE evaluation. Although validity has been demonstrated
      before, we provide evidence that 3DTEE is reproducible among 15 observers and is
      a reliable method for MVP evaluation.

PMID- 24028386
TI  - Unidirectional control of anisotropic wetting through surface modification of
      PDMS microstructures.
AB  - It has been shown before that anisotropically microstructured surfaces exhibit
      anisotropic wetting phenomena. This study presents a possibility to control the
      anisotropy of wetting by tailoring the surface chemistry. PDMS microchannels were
      permanently hydrophilized and subsequently functionalized further. Thereby,
      systematic studies on the effect of the surface modification on the wetting
      properties of microstructures have been possible. Importantly, we found that the
      wetting parallel to the groove strongly depended on the chemical modification of
      the structure although the wetting perpendicular to the groove is almost
      unaffected. Through immobilization of a monolayer of Si nanoparticles (SiNPs)
      exclusively on the elevations of the hydrogel-coated microstructured PDMS
      substrate, the anisotropic wetting could be selectively altered unidirectionally
      along the pattern direction. 

PMID- 24028388
TI  - NIR Schottky photodetectors based on individual single-crystalline GeSe
      nanosheet.
AB  - We have synthesized high-quality, micrometer-sized, single-crystal GeSe
      nanosheets using vapor transport and deposition techniques. Photoresponse is
      investigated based on mechanically exfoliated GeSe nanosheet combined with Au
      contacts under a global laser irradiation scheme. The nonlinearship, asymmetric,
      and unsaturated characteristics of the I-V curves reveal that two uneven back-to
      back Schottky contacts are formed. First-principles calculations indicate that
      the occurrence of defects-induced in-gap defective states, which are responsible
      for the slow decay of the current in the OFF state and for the weak light
      intensity dependence of photocurrent. The Schottky photodetector exhibits a
      marked photoresponse to NIR light illumination (maximum photoconductive gain ~5.3
      * 10(2) % at 4 V) at a wavelength of 808 nm. The significant photoresponse and
      good responsitivity (~3.5 A W(-1)) suggests its potential applications as
      photodetectors. 

PMID- 24028387
TI  - Oral treatment with beta-lactoglobulin peptides prevents clinical symptoms in a
      mouse model for cow's milk allergy.
AB  - BACKGROUND: Prior exposure to partial whey hydrolysates has been shown to reduce
      the allergic response to whey in mice. This effect was more pronounced in
      combination with a diet containing non-digestible oligosaccharides
      (scGOS/lcFOS/pAOS). It is unknown which fractions/epitopes are responsible for
      this effect. Therefore, the prophylactic ability of synthetic peptides of beta
      lactoglobulin with/without a scGOS/lcFOS/pAOS-containing diet to reduce the
      allergic response in a mouse model for cow's milk allergy was investigated.
      METHODS: Of 31 peptides, nine peptides were selected based on human T cell data.
      Mice were pre-treated orally with three peptide mixtures or single peptides for
      six consecutive days. During this period, they received a control or
      scGOS/lcFOS/pAOS-containing diet. Subsequently, mice were orally sensitized to
      whey and received an intradermal and oral challenge. After sacrifice, serum and
      mesenteric lymph nodes (MLN) were collected for further analysis. RESULTS: Prior
      exposure to peptide mixtures 1 and 3 significantly reduced the acute allergic
      skin response to whey. Mixture 2 showed no effect. An additive effect of the
      scGOS/lcFOS/pAOS-containing diet was only observed for mixture 1. Of the peptides
      in mixture 1, one peptide (LLDAQSAPLRVYVEELKP) showed the strongest effect on the
      acute allergic skin response. This peptide also tended to decrease whey-specific
      antibody levels and to increase the percentages of CD11b+CD103+ dendritic cells
      and CD25+Foxp3+ T cells in the MLN. CONCLUSIONS: Prior exposure to specific
      peptides of beta-lactoglobulin reduces the allergic response to whey, which may
      involve regulatory dendritic and T cells. Combining peptides with a
      sGOS/lcFOS/pAOS-containing diet enhances this effect.

PMID- 24028389
TI  - Transcriptome resources for the frogs Lithobates clamitans and Pseudacris
      regilla, emphasizing antimicrobial peptides and conserved loci for phylogenetics.
AB  - We developed genetic resources for two North American frogs, Lithobates clamitans
      and Pseudacris regilla, widespread native amphibians that are potential indicator
      species of environmental health. For both species, mRNA from multiple tissues was
      sequenced using 454 technology. De novo assemblies with Mira3 resulted in 50 238
      contigs (N50 = 687 bp) and 48 213 contigs (N50 = 686 bp) for L. clamitans and P.
      regilla, respectively, after clustering with CD-Hit-EST and purging contigs below
      200 bp. We performed BLASTX similarity searches against the Xenopus tropicalis
      proteome and, for predicted ORFs, HMMER similarity searches against the Pfam-A
      database. Because there is broad interest in amphibian immune factors, we
      manually annotated putative antimicrobial peptides. To identify conserved regions
      suitable for amplicon resequencing across a broad taxonomic range, we performed
      an additional assembly of public short-read transcriptome data derived from two
      species of the genus Rana and identified reciprocal best TBLASTX matches among
      all assemblies. Although P. regilla, a hylid frog, is substantially more diverged
      from the ranid species, we identified 56 genes that were sufficiently conserved
      to allow nondegenerate primer design with Primer3. In addition to providing a
      foundation for comparative genomics and quantitative gene expression analysis,
      our results enable quick development of nuclear sequence-based markers for
      phylogenetics or population genetics. 

PMID- 24028390
TI  - Myocardial contusion and rib fracture repair in an adult horse.
AB  - OBJECTIVE: To describe the clinical findings and management of myocardial injury
      secondary to blunt thoracic trauma and rib fracture in an adult horse. CASE
      SUMMARY: A 6-year-old Warmblood gelding presented for treatment of blunt thoracic
      trauma. Sonographic examination of the thorax revealed a complete, mildly
      comminuted fracture of the left 5th rib with a fragment overlying the left atrium
      and coronary artery, hemothorax, and subjective left ventricular dyskinesis.
      Evidence of myocardial injury included atrial fibrillation, ventricular ectopy,
      and increased plasma cardiac troponin I concentration. The rib fracture was
      repaired under general anesthesia using a wire and plate technique. The atrial
      fibrillation converted to normal sinus rhythm coincidentally with intraoperative
      local infusion of mepivicaine in administration of intercostal perineural
      analgesia. Continuous, resting, and exercising electrocardiograms, serial cardiac
      troponin I concentrations and echocardiograms were used to monitor the myocardial
      injury. The horse was discharged after 5 days of hospitalization. Reexaminations
      3 and 15 months after the initial trauma showed healing of the fracture and no
      evidence of myocardial sequelae. NEW OR UNIQUE INFORMATION PROVIDED: To our
      knowledge, this is the first documentation of the diagnosis and monitoring of
      myocardial injury secondary to blunt thoracic trauma, as well as surgical repair
      of a rib fracture in an adult horse. Rib fractures and myocardial trauma can be
      successfully managed in adult horses and myocardial injury should be considered
      in cases of thoracic trauma.

PMID- 24028391
TI  - Impulsivity in bipolar disorder: relationships with neurocognitive dysfunction
      and substance use history.
AB  - OBJECTIVES: Impulsivity is a core feature in bipolar disorder. Although mood
      symptoms exacerbate impulsivity, self-reports of impulsivity are elevated, even
      during euthymia. Neurocognitive processes linked to impulsivity (e.g., attention,
      inhibition) are also impaired in patients with bipolar disorder, and a high
      frequency of comorbidities associated with impulsivity, such as substance use
      disorders, further highlights the clinical relevance of this dimension of the
      illness. Our objective was to assess the relationship between impulsivity and
      cognition in bipolar disorder. METHODS: We evaluated impulsivity in 98 patients
      with bipolar disorder and its relationship with symptoms, cognition, and
      substance use history. We assessed self-reports of trait impulsivity [Barrett
      Impulsiveness Scale (BIS)] and impulsive behaviors on the Iowa Gambling Task
      (IGT). A comprehensive clinical and neurocognitive battery was also completed.
      Patients were compared with 95 healthy controls. RESULTS: Patients with bipolar
      disorder had higher scores versus healthy controls on all BIS scales. Performance
      on the IGT was significantly impaired and patients showed a tendency toward more
      erratic choices. Depressive symptoms were positively correlated with trait
      impulsivity and with an increased tendency to attend more readily to losses
      versus gains on the IGT. We found no significant associations between impulsivity
      and neurocognition in the full bipolar sample; however, when sub-grouped based on
      substance abuse history, significant relationships were revealed only in subjects
      without a substance abuse history. CONCLUSIONS: Our data support prior reports of
      increased trait impulsivity and impairment on behavioral tasks of impulsiveness
      in bipolar disorder and suggest a differential relationship between these illness
      features that is dependent upon history of substance abuse.

PMID- 24028393
TI  - Half full or empty: cues that lead wine drinkers to unintentionally overpour.
AB  - Wine drinkers often pour their own wine, but is the amount they pour influenced
      by the shape of the glass, the color of the wine, or how they pour? Building on
      research involving visual illusions and haptic cues, an exploratory field study
      shows that while wine drinkers typically poured 3.95 fl. oz. of wine into a
      standard baseline (10 fl. oz.) glass, they poured 11.9% more into a wider glass,
      9.2% more when the wine was white (the low contrast with the glass makes it
      difficult to see), and 12.2% more when the wine glass was held in their hand
      rather than sitting on the table. Using narrower wine glasses and not pouring
      while holding one's glass may be steps toward modestly reducing the amount of
      wine a social drinker pours and drinks.

PMID- 24028392
TI  - Full-length dysferlin expression driven by engineered human dystrophic blood
      derived CD133+ stem cells.
AB  - The protein dysferlin is abundantly expressed in skeletal and cardiac muscles,
      where its main function is membrane repair. Mutations in the dysferlin gene are
      involved in two autosomal recessive muscular dystrophies: Miyoshi myopathy and
      limb-girdle muscular dystrophy type 2B. Development of effective therapies
      remains a great challenge. Strategies to repair the dysferlin gene by skipping
      mutated exons, using antisense oligonucleotides (AONs), may be suitable only for
      a subset of mutations, while cell and gene therapy can be extended to all
      mutations. AON-treated blood-derived CD133+ stem cells isolated from patients
      with Miyoshi myopathy led to partial dysferlin reconstitution in vitro but failed
      to express dysferlin after intramuscular transplantation into scid/blAJ dysferlin
      null mice. We thus extended these experiments producing the full-length dysferlin
      mediated by a lentiviral vector in blood-derived CD133+ stem cells isolated from
      the same patients. Transplantation of engineered blood-derived CD133+ stem cells
      into scid/blAJ mice resulted in sufficient dysferlin expression to correct
      functional deficits in skeletal muscle membrane repair. Our data suggest for the
      first time that lentivirus-mediated delivery of full-length dysferlin in stem
      cells isolated from Miyoshi myopathy patients could represent an alternative
      therapeutic approach for treatment of dysferlinopathies.

PMID- 24028394
TI  - Examining substance use among rural Appalachian and urban non-Appalachian
      individuals participating in drug court.
AB  - The study purpose was to examine differences in substance use among individuals
      in drug court (N = 583) in rural Appalachian (n = 301) and urban non-Appalachian
      areas (n = 282). A series of logistic regression analyses suggested individuals
      in the rural Appalachian area were significantly more likely to report lifetime
      use of cocaine, illicit opiates, and illicit benzodiazepines, but they were less
      likely to report methamphetamine use when compared with individuals in the urban
      non-Appalachian area. Regarding past 30-day use, a series of logistic regression
      analyses suggested individuals in the rural Appalachian area were significantly
      more likely to use marijuana, illicit opiates, and illicit benzodiazepines, but
      they were less likely to report crack cocaine use when compared with individuals
      in the urban non-Appalachian area. Identifying differences which exist in
      substance use is the first step in generating evidence-based structural changes
      in treatment drug court programs. Future research should focus on better
      understanding context in terms of demographic, geographic, and economic
      conditions, which may be of critical influence on substance use and treatment
      planning. 

PMID- 24028395
TI  - Children of Substance-Abusing Parents: Dynamics and TreatmentChildren of
      Substance-Abusing Parents: Dynamics and Treatment.

PMID- 24028396
TI  - Murine mast cells secrete and respond to interleukin-33.
AB  - Interleukin-33 (IL-33) appears to play a crucial role in the expression of
      allergic diseases, but its cellular source and regulatory mechanisms remain to be
      fully elucidated. Mast cells, one of the major effecter cell populations in
      mediating allergy, express high levels of IL-33 receptor, ST2, and have been
      shown to express IL-33 transcripts. In this study, we aimed to examine the
      secretion of IL-33 in mast cells and their response to IL-33. We have
      successfully detected secreted IL-33 from cell supernatants through a modified
      enzyme-linked immunosorbent assay (ELISA) technique-cell-based ELISA. Activation
      of bone marrow-derived cultured mast cells (BMMCs) by crosslinkage of an antigen
      [ovalbumin (OVA)] and OVA-specific IgE mAbs significantly induced the expression
      of IL-33 transcripts, cytosolic and secreted proteins. In addition, the Toll-like
      receptor (TLR) 2 and TLR-9 ligands could trigger IL-33 mRNA expression. Exposure
      of BMMCs to IL-33 significantly increased the levels of IL-13 and IL-6
      expression, concomitant with enhanced activation of mitogen-activated protein
      kinase (MAPKs) (ERK, p38, and JNK) and nuclear factor-kappa B. These results
      suggest that mouse BMMCs are capable of producing and serving as endogenous
      sources of IL-33, and that IL-33 plays an important role in regulating mast cell
      functions. 

PMID- 24028397
TI  - Increased rate of day surgery use for inguinal and femoral hernia repair in a
      decade of hospital admissions in the Veneto Region (north-east Italy): a record
      linkage study.
AB  - BACKGROUND: Worldwide, there has been a marked increase in the number of inguinal
      and femoral hernia repairs performed as day surgery procedures. This study aimed
      to outline the epidemiology of the procedures for repairing unilateral inguinal
      and femoral hernia in the Veneto Region, and to analyze the time trends and
      organizational appropriateness of these procedures. METHODS: Drawing from the
      anonymous computerized database of hospital discharge records for the Veneto
      Region, we identified all unilateral groin hernia repair procedures completed in
      Veneto residents between 2000 and 2009 at both public and accredited private
      hospitals. RESULTS: A total 141,329 hernias were repaired in the Veneto Region
      during the decade considered, with an annual rate of 291.2 per 100,000 population
      for inguinal hernia (IH) repairs and 11.2 per 100,000 population for femoral
      hernia (FH) repairs. Day surgery was used more for inguinal than for femoral
      hernia repairs, accounting for 76% and 43% (p< 0.05), respectively, of all hernia
      repair procedures completed during the period. The % of other than surgery
      hospital ordinary admissions (day surgery or ambulatory surgery) during the
      decade considered rose from 61.7% to 86.7% for IH and from 33.0% to 61.8% for FH.
      CONCLUSIONS: In the last decade, the Veneto Region has reduced the rate of
      ordinary hospital admissions for groin hernia repair with a view to improving the
      efficiency of the hospital network.

PMID- 24028398
TI  - Prevalence of avian paramyxovirus type 1 in Mallards during autumn migration in
      the western Baltic Sea region.
AB  - BACKGROUND: Newcastle disease virus (NDV) is the causative agent of the Newcastle
      disease, a severe disease in birds associated with substantial economic losses to
      the poultry industry worldwide. Sweden is situated along the Western European
      waterfowl flyway and applies a non-vaccination policy combined with directives of
      immediate euthanisation of NDV infected flocks. During the last decades there
      have been several outbreaks with NDV in poultry in Sweden. However, less is known
      about the virus prevalence in the wild bird population including waterfowl, a
      well-established reservoir of avian paramyxovirus type 1 (APMV-1), the
      paramyxovirus serotype that include pathogenic NDV. METHODS: The survey
      constituted of 2332 samples from Mallards (Anas platyrhynchos), trapped in the
      southern part of Sweden during autumn migration in 2010. These samples were
      screened for APMV-1 by real-time reverse transcription PCR, and viral strains
      from positive samples were isolated and characterized by sequence analysis of the
      fusion gene and by phylogenetic analysis. CONCLUSIONS: Twenty of these samples
      were positive for APMV-1, hence a virus prevalence of 0.9% (95% Confidence
      Interval [95% CI]=0.54%, 1.35%). The highest APMV-1 prevalence was detected in
      juvenile Mallards sampled in November (n=887, prevalence 1.24% ([95% CI])=0.67%,
      2.24%). Sequence analysis and evaluation of phylogenetic relatedness indicated
      that isolated APMV-1 strains were lentogenic, and phylogenetically most closely
      related to genotype Ib strains within the clade of class II viruses. The sampling
      system employed enabled us to follow APMV-1 infections and the shedding of one
      particular viral strain in one individual bird over several days. Furthermore,
      combining previous screening results with the APMV-1 detections in this study
      showed that more than 50% of Mallards that tested positive for APMV-1 RNA were co
      infected with influenza A virus.

PMID- 24028401
TI  - Abstracts of the Biennial Spring Conference of the Australasian College of
      Dermatologists. October 3-6, 2013. Cairns, Queensland, Australia.

PMID- 24028400
TI  - Hypopituitarism in pediatric survivors of inflicted traumatic brain injury.
AB  - Endocrine dysfunction is common after accidental traumatic brain injury (TBI).
      Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI)
      is not known. The aim of this study was to examine endocrinopathy in children
      after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated
      for growth/endocrine dysfunction, including anthropometric measurements and
      hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning
      and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor
      1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine
      osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as
      appropriate. Eighty-six percent of subjects had endocrine dysfunction with at
      least one abnormality, whereas 50% had two or more abnormalities, significantly
      increased compared to an estimated 2.5% with endocrine abnormality in the general
      population (p<0.001). Elevated prolactin was common (64%), followed by abnormal
      thyroid function (33%), short stature (29%), and low GH peak (17%). High
      prolactin was common in subjects with other endocrine abnormalities. Two were
      treated with thyroid hormone and 2 may require GH therapy. In conclusion,
      children with a history of iTBI show high risk for endocrine dysfunction,
      including elevated PRL and growth abnormalities. This effect of iTBI has not been
      well described in the literature. Larger, multi-center, prospective studies would
      provide more data to determine the extent of endocrine dysfunction in iTBI. We
      recommend that any child with a history of iTBI be followed closely for growth
      velocity and pubertal changes. If growth velocity is slow, PRL level and a full
      endocrine evaluation should be performed.

PMID- 24028402
TI  - Effect of dietary nonphytate phosphorus on laying performance and small
      intestinal epithelial phosphate transporter expression in Dwarf pink-shell laying
      hens.
AB  - This study examined the effects of various levels of dietary nonphytate
      phosphorus on laying performance and the expression patterns of phosphorus
      metabolism related genes in Dwarf pink-shell laying hens. A total of 405 28-week
      old Dwarf pink-shell laying hens were fed the same corn-soybean basal meals but
      containing 0.20%, 0.25%, 0.30%, 0.35% or 0.40% nonphytate phosphorus. The results
      showed that feed intake, egg production, and average egg weights were
      quadratically correlated with dietary nonphytate phosphorus content (P < 0.05),
      and the highest egg production, feed intake and average egg weights were achieved
      when dietary nonphytate phosphorus was at 0.3% (P < 0.05). mRNA expression of
      intestinal sodium phosphorus co-transporter linearly decreased when dietary
      nonphytate phosphorus increased. mRNA and protein expression of intestinal
      calbindin and vitamin D receptor correlated quadratically with dietary nonphytate
      phosphorus, and the highest expression was found when dietary available
      phosphorus was at 0.25% to 0.3%. In conclusion, the ideal phosphorus requirement
      for Dwarf pink-shell layer hens is estimated to be 0.3% in a corn-soybean diet.
      With this level of phosphorus supplementation, calbindin and vitamin D receptor
      reached their highest expression. 

PMID- 24028403
TI  - Communicable disease control in Afghanistan.
AB  - Among public health challenges in Afghanistan, communicable diseases still
      predominate because the epidemiologic transition to chronic disease has not yet
      occurred. Afghanistan's 10-year journey to improve its response to communicable
      disease is reflected in varying degrees of progress and innovation, all while
      long-standing conflict and geographic inaccessibility limit outreach and
      effective service delivery to vulnerable populations. Although Afghanistan is
      close to achieving polio elimination, other reportable communicable diseases are
      only slowly achieving their goals and objectives through targeted, sustained
      programmatic efforts. The introduction of disease early warning systems has
      allowed for identification and investigation of outbreaks within 48 hours.
      Tuberculosis case detection has risen over the last 10 years, and treatment
      success rates have been sustained at World Health Organization targets over the
      last 5 years at 85%. These successes are in large part due to increased
      government commitment, Global Fund support, training of community health workers
      and improved laboratory capabilities. Malaria cases dropped between 2002 and
      2010. HIV/AIDS has been kept at low levels except in only certain sub-sectors of
      the population. In order to build on these achievements, Afghanistan will need a
      comprehensive strategy for all communicable diseases, with better human and
      infrastructure development, better multi-sectoral development and international
      collaboration. 

PMID- 24028404
TI  - Superaromatic stabilization energy as a novel local aromaticity index for
      polycyclic aromatic hydrocarbons.
AB  - Superaromatic stabilization energy (SSE), previously proposed by us, can be used
      as a novel local aromaticity index for benzene rings in polycyclic aromatic
      hydrocarbons (PAHs). SSE can be interpreted as the first local aromaticity index
      explicitly related to all relevant circuits in a polycyclic pi-system, an origin
      of local aromaticity, being free of local aromaticity arising from adjacent six
      site circuits. Therefore, this quantity is best suited for characterizing the
      electronic structure of large pericondensed PAHs and graphene nanoflakes. 

PMID- 24028405
TI  - Entropic origin of cobalt-carbon bond cleavage catalysis in adenosylcobalamin
      dependent ethanolamine ammonia-lyase.
AB  - Adenosylcobalamin-dependent enzymes accelerate the cleavage of the cobalt-carbon
      (Co-C) bond of the bound coenzyme by >10(10)-fold. The cleavage-generated 5'
      deoxyadenosyl radical initiates the catalytic cycle by abstracting a hydrogen
      atom from substrate. Kinetic coupling of the Co-C bond cleavage and hydrogen-atom
      transfer steps at ambient temperatures has interfered with past experimental
      attempts to directly address the factors that govern Co-C bond cleavage
      catalysis. Here, we use time-resolved, full-spectrum electron paramagnetic
      resonance spectroscopy, with temperature-step reaction initiation, starting from
      the enzyme-coenzyme-substrate ternary complex and (2)H-labeled substrate, to
      study radical pair generation in ethanolamine ammonia-lyase from Salmonella
      typhimurium at 234-248 K in a dimethylsulfoxide/water cryosolvent system. The
      monoexponential kinetics of formation of the (2)H- and (1)H-substituted substrate
      radicals are the same, indicating that Co-C bond cleavage rate-limits radical
      pair formation. Analysis of the kinetics by using a linear, three-state model
      allows extraction of the microscopic rate constant for Co-C bond cleavage. Eyring
      analysis reveals that the activation enthalpy for Co-C bond cleavage is 32 +/- 1
      kcal/mol, which is the same as for the cleavage reaction in solution. The origin
      of Co-C bond cleavage catalysis in the enzyme is, therefore, the large, favorable
      activation entropy of 61 +/- 6 cal/(mol.K) (relative to 7 +/- 1 cal/(mol.K) in
      solution). This represents a paradigm shift from traditional, enthalpy-based
      mechanisms that have been proposed for Co-C bond-breaking in B12 enzymes. The
      catalysis is proposed to arise from an increase in protein configurational
      entropy along the reaction coordinate. 

PMID- 24028407
TI  - Enhanced CO2 capture in binary mixtures of 1-alkyl-3-methylimidazolium
      tricyanomethanide ionic liquids with water.
AB  - Absorption of carbon dioxide and water in 1-butyl-3-methylimidazoliun
      tricyanomethanide ([C4C1im][TCM]) and 1-octyl-3-methylimidazolium
      tricyanomethanide ([C8C1im][TCM]) ionic liquids (ILs) was systematically
      investigated for the first time as a function of the H2O content by means of a
      gravimetric system together with in-situ Raman spectroscopy, excess molar volume
      (V(E)), and viscosity deviation measurements. Although CO2 absorption was
      marginally affected by water at low H2O molar fractions for both ILs, an increase
      of the H2O content resulted in a marked enhancement of both the CO2 solubility
      (ca. 4-fold) and diffusivity (ca. 10-fold) in the binary [C(n)C1im][TCM]/H2O
      systems, in contrast to the weak and/or detrimental influence of water in most
      physically and chemically CO2-absorbing ILs. In-situ Raman spectroscopy on the
      IL/CO2 systems verified that CO2 is physically absorbed in the dry ILs with no
      significant effect on their structural organization. A pronounced variation of
      distinct tricyanomethanide Raman modes was disclosed in the [C(n)C1im][TCM]/H2O
      mixtures, attesting to the gradual disruption of the anion-cation coupling by the
      hydrogen-bonded water molecules to the [TCM](-) anions, in accordance with the
      positive excess molar volumes and negative viscosity deviations for the binary
      systems. Most importantly, CO2 absorption in the ILs/H2O mixtures at high water
      concentrations revealed that the [TCM](-) Raman modes tend to restore their
      original state for the heavily hydrated ILs, in qualitative agreement with the
      intriguing nonmonotonous transients of CO2 absorption kinetics unveiled by the
      gravimetric measurements for the hybrid solvents. A molecular exchange mechanism
      between CO2 in the gas phase and H2O in the liquid phase was thereby proposed to
      explain the enhanced CO2 absorption in the hybrid [C(n)C1im][TCM]//H2O solvents
      based on the subtle competition between the TCM-H2O and TCM-CO2 interactions,
      which renders these ILs very promising for CO2 separation applications.

PMID- 24028409
TI  - Nursing work.

PMID- 24028406
TI  - Epigenetics, oestradiol and hippocampal memory consolidation.
AB  - Epigenetic alterations of histone proteins and DNA are essential for hippocampal
      synaptic plasticity and cognitive function, and contribute to the aetiology of
      psychiatric disorders and neurodegenerative diseases. Hippocampal memory
      formation depends on histone alterations and DNA methylation, and increasing
      evidence suggests that the regulation of these epigenetic processes by modulatory
      factors, such as environmental enrichment, stress and hormones, substantially
      influences memory function. Recent work from our laboratory suggests that the
      ability of the sex-steroid hormone 17beta-oestradiol (E2 ) to enhance novel
      object recognition memory consolidation in young adult female mice is dependent
      on histone H3 acetylation and DNA methylation in the dorsal hippocampus. Our data
      also suggest that enzymes mediating DNA methylation and histone acetylation work
      in concert to regulate the effects of E2 on memory consolidation. These findings
      shed light on the epigenetic mechanisms that influence hormonal modulation of
      cognitive function, and may have important implications for understanding how
      hormones influence cognition in adulthood and ageing. The present review provides
      a brief overview of the literature on epigenetics and memory, describes in detail
      our findings demonstrating that epigenetic alterations regulate E2 -induced
      memory enhancement in female mice, and discusses future directions for research
      on the epigenetic regulation of E2 -induced memory enhancement. 

PMID- 24028408
TI  - Imaging of thyroid tumor angiogenesis with microbubbles targeted to vascular
      endothelial growth factor receptor type 2 in mice.
AB  - BACKGROUND: To evaluate whether Contrast Enhanced Ultrasund (CEUS) with
      microbubbles (MBs) targeted to VEGFR-2 is able to characterize in vivo the VEGFR
      2 expression in the tumor vasculature of a mouse model of thyroid cancer (Tg-TRK
      T1). METHODS: Animal protocol was approved by Institutional committee on
      Laboratory Animal Care. Contrast-enhanced ultrasound imaging with MBs targeted
      with an anti-VEGFR-2 monoclonal antibody (UCAVEGFR-2) and isotype control
      antibody (UCAIgG) was performed in 7 mice with thyroid carcinoma, 5 mice with
      hyperplasia or benign thyroid nodules and 4 mice with normal thyroid. After
      ultrasonography, the tumor samples were harvested for histological examination
      and VEGFR-2 expression was tested by immunohistochemistry. Data were reported as
      median and range. Paired non parametric Wilcoxon's test and ANOVA of Kruskal
      Wallis were used. The correlation between the contrast signal and the VEGFR-2
      expression was assessed by the Spearman coefficient. RESULTS: The Video intensity
      difference (VID) caused by backscatter of the retained UCAVEGFR-2 was
      significantly higher in mice harboring thyroid tumors compared to mice with
      normal thyroids (P < 0.01) and to mice harboring benign nodules (P < 0.01). No
      statistically significant differences of VID were observed in the group of mice
      carrying benign nodules compared to mice with normal thyroids. Moreover in
      thyroid tumors VID of retained VEGFR-2-targeted UCA was significantly higher than
      that of control UCAIgG (P <0.05). Results of immunohistochemical analysis
      confirmed VEGFR-2 overexpression. The magnitude of the molecular ultrasonographic
      signal from a VEGFR-2-targeted UCA retained by tissue correlates with VEGFR-2
      expression determined by immunohistochemistry (rho 0.793, P=0.0003). CONCLUSIONS:
      We demonstrated that CEUS with UCAVEGFR-2 might be used for in vivo non invasive
      detection and quantification of VEGFR-2 expression in thyroid cancer in mice, and
      to differentiate benign from malignant thyroid nodules.

PMID- 24028410
TI  - Fear on the move: predator hunting mode predicts variation in prey mortality and
      plasticity in prey spatial response.
AB  - Ecologists have long searched for a framework of a priori species traits to help
      predict predator-prey interactions in food webs. Empirical evidence has shown
      that predator hunting mode and predator and prey habitat domain are useful traits
      for explaining predator-prey interactions. Yet, individual experiments have yet
      to replicate predator hunting mode, calling into question whether predator
      impacts can be attributed to hunting mode or merely species identity. We tested
      the effects of spider predators with sit-and-wait, sit-and-pursue and active
      hunting modes on grasshopper habitat domain, activity and mortality in a
      grassland system. We replicated hunting mode by testing two spider predator
      species of each hunting mode on the same grasshopper prey species. We observed
      grasshoppers with and without each spider species in behavioural cages and
      measured their mortality rates, movements and habitat domains. We likewise
      measured the movements and habitat domains of spiders to characterize hunting
      modes. We found that predator hunting mode explained grasshopper mortality and
      spider and grasshopper movement activity and habitat domain size. Sit-and-wait
      spider predators covered small distances over a narrow domain space and killed
      fewer grasshoppers than sit-and-pursue and active predators, which ranged farther
      distances across broader domains and killed more grasshoppers, respectively. Prey
      adjusted their activity levels and horizontal habitat domains in response to
      predator presence and hunting mode: sedentary sit-and-wait predators with narrow
      domains caused grasshoppers to reduce activity in the same-sized domain space;
      more mobile sit-and-pursue predators with broader domains caused prey to reduce
      their activity within a contracted horizontal (but not vertical) domain space;
      and highly mobile active spiders led grasshoppers to increase their activity
      across the same domain area. All predators impacted prey activity, and sit-and
      pursue predators generated strong effects on domain size. This study demonstrates
      the validity of utilizing hunting mode and habitat domain for predicting predator
      prey interactions. Results also highlight the importance of accounting for
      flexibility in prey movement ranges as an anti-predator response rather than
      treating the domain as a static attribute. 

PMID- 24028411
TI  - Addition of nucleophiles to phosphanido derivatives of Pt(III): formation of P-C,
      P-N, and P-O bonds.
AB  - The reactivity of the dinuclear platinum(III) derivative [(R(F))2Pt(III)(MU
      PPh2)2Pt(III)(R(F))2](Pt-Pt) (R(F) = C6F5) (1) toward OH(-), N3(-), and NCO(-)
      was studied. The coordination of these nucleophiles to a metal center evolves
      with reductive coupling or reductive elimination between a bridging
      diphenylphosphanido group and OH(-), N3(-), and NCO(-) or C6F5 groups and
      formation of P-O, P-N, or P-C bonds. The addition of OH(-) to 1 evolves with a
      reductive coupling with the incoming ligand, formation of a P-O bond, and the
      synthesis of [NBu4]2[(R(F))2Pt(II)(MU-OPPh2)(MU-PPh2)Pt(II)(R(F))2] (3). The
      addition of N3(-) takes place through two ways: (a) formation of the P-N bond and
      reductive elimination of PPh2N3 yielding [NBu4]2[(R(F))2Pt(II)(MU-N3)(MU
      PPh2)Pt(II)(R(F))2] (4a) and (b) formation of the P-C bond and reductive coupling
      with one of the C6F5 groups yielding [NBu4][(R(F))2Pt(II)(MU-N3)(MU
      PPh2)Pt(II)(R(F))(PPh2R(F))] (4b). Analogous behavior was shown in the addition
      of NCO(-) to 1 which afforded [NBu4]2[(R(F))2Pt(II)(MU-NCO)(MU
      PPh2)Pt(II)(R(F))2] (5a) and [NBu4][(R(F))2Pt(II)(MU-NCO)(MU
      PPh2)Pt(II)(R(F))(PPh2R(F))] (5b). In the reaction of the trinuclear complex
      [(R(F))2Pt(III)(MU-PPh2)2Pt(III)(MU-PPh2)2Pt(II)(R(F))2](Pt(III)-Pt(III)) (2)
      with OH(-) or N3(-), the coordination of the nucleophile takes place selectively
      at the central platinum(III) center, and the PPh2/OH(-) or PPh2/N3(-) reductive
      coupling yields the trinuclear [NBu4]2[(R(F))2Pt(II)(MU-Ph2PO)(MU-PPh2)Pt(II)(MU
      PPh2)2Pt(II)(R(F))2] (6) and [NBu4][(R(F))2Pt(1)(MU3-Ph2PNPPh2)(MU-PPh2)Pt(2)(MU
      PPh2)Pt(3)(R(F))2](Pt(2)-Pt(3)) (7). Complex 7 is fluxional in solution, and an
      equilibrium consisting of Pt-Pt bond migration was ascertained by (31)P EXSY
      experiments.

PMID- 24028412
TI  - Nanoscale mechano-electronic behavior of a metalloprotein as a variable of metal
      content.
AB  - In this work, we have explored an approach to finding a correlation between the
      mechanical response of a metalloprotein against a range of applied force (by
      force curve analysis) and its electrical response under pressure stimulation (by
      current sensing atomic force spectroscopy) at the nanoscale. Iron-storage protein
      ferritin has been chosen as an experimental model system because it naturally
      contains a semiconducting iron core. This core consists of a large number of iron
      atoms and is therefore expected to exert a clear influence on the overall
      mechanical response of the protein structure. Four different ferritins
      (apoferritin, Fe(III)-ferritins containing ~750 and ~1400 iron atoms, and
      holoferritin containing ~2600 iron atoms) were chosen in order to identify any
      relation between the mechano-electronic behavior of the ferritins and their metal
      content. We report the measurement of Young's modulus values of the ferritin
      proteins as applicable in a nanoscale environment, for the first time, and show
      that these values are directly linked to the iron content of the individual
      ferritin type. The greater the iron content, the greater the Young's modulus and
      in general the slower the rate of deformation against the application of force.
      When compressed, all the four ferritins exhibited increased electronic
      conductivity. A correlation between the iron content of the ferritins and the
      current values observed at certain bias voltages could be made at higher bias
      values (beyond 0.7 V), but no such discrimination among the four compressed
      ferritins could be made at the lower voltages. We propose that only at higher
      voltages can the iron atoms that reside deeper inside the core of the ferritins
      be accessed. The iron atoms that could be situated at the inner wall of the
      protein shell appear to make a general contribution to the electronic
      conductivity of the four ferritin systems.

PMID- 24028413
TI  - Left ventricular strain examination of different aged adults with 3D speckle
      tracking echocardiography.
AB  - The purpose of this study was to identify traits of the left ventricular (LV)
      global longitudinal strain (GLS), global radial strain (GRS), global circular
      strain (GCS), and global area tracking (GAT) with three-dimensional speckle
      tracking echocardiography (3DSTE), and to determine the relationship between
      strain and age in healthy adults of different ages. A total of 153 volunteers
      were divided into young adult, middle-aged, and elderly groups, and examined with
      echocardiography to obtain general data and live two-dimensional (2D) images of
      the apical four-chamber view, which were assembled to obtain the full volume view
      of the LV. The images were then analyzed with 3DSTE software. Compared with the
      young adult and middle-aged groups, elderly adults demonstrated lower GLS, GRS,
      GCS, and GAT. Significant differences were not noted in GLS, GRS, and GCS between
      the young adult and middle-aged groups; however, the GAT of the middle-aged group
      was lower than that of the young adult group. The longitudinal strain (LS),
      radial strain (RS), and area tracking (AT) of 16 LV segments of the young adult
      group decreased gradually in level from the mitral valve to the apex, and
      increased in circular strain (CS). The LS, RS, CS, and AT of the middle-aged
      group also decreased gradually. The LS, RS, CS, and AT of the elderly people were
      highest from the mitral valve to the apex level and lowest at the papillary
      muscle. The results of this study demonstrated that LV GLS, GRS, GCS, and GAT
      decrease with age. 

PMID- 24028415
TI  - Clinical features of bilateral rhegmatogenous retinal detachments.

PMID- 24028414
TI  - Total or Partial Knee Arthroplasty Trial - TOPKAT: study protocol for a
      randomised controlled trial.
AB  - BACKGROUND: In the majority of patients with osteoarthritis of the knee the
      disease originates in the medial compartment. There are two fundamentally
      different approaches to knee replacement for patients with unicompartmental
      disease: some surgeons feel that it is always best to replace both the knee
      compartments with a total knee replacement (TKR); whereas others feel it is best
      to replace just the damaged component of the knee using a partial or
      unicompartment replacement (UKR). Both interventions are established and well
      documented procedures. Little evidence exists to prove the clinical and cost
      effectiveness of either management option. This provides an explanation for the
      high variation in treatment of choice by individual surgeons for the same knee
      pathology.The aim of the TOPKAT study will be to assess the clinical and cost
      effectiveness of TKRs compared to UKRs in patients with medial compartment
      osteoarthritis. METHODS/DESIGN: The design of the study is a single layer
      multicentre superiority type randomised controlled trial of unilateral knee
      replacement patients. Blinding will not be possible as the surgical scars for
      each procedure differ.We aim to recruit 500 patients from approximately 28
      secondary care orthopaedic units from across the UK including district general
      and teaching hospitals. Participants will be randomised to either UKR or TKR.
      Randomisation will occur using a web-based randomisation system. The study is
      pragmatic in terms of implant selection for the knee replacement operation.
      Participants will be followed up for 5 years. The primary outcome is the Oxford
      Knee Score, which will be collected via questionnaires at 2 months, 1 year and
      then annually to 5 years. Secondary outcomes will include cost-effectiveness,
      patient satisfaction and complications data. TRIAL REGISTRATION: Current
      Controlled Trials ISRCTN03013488; ClinicalTrials.gov Identifier: NCT01352247.

PMID- 24028416
TI  - Multivariate analysis of spectral data with frequency shifts: application to
      temperature dependent infrared spectra of peptides and proteins.
AB  - Changes in the amide I' IR band with temperature are widely used for elucidation
      of peptide and protein conformational transitions and folding equilibria. Since
      amide I' exhibits inherent temperature dependent frequency shifts, standard
      mixture analysis methods are not applicable. To reliably extract the true
      thermodynamic states, frequency shifts of the component spectra must be
      explicitly taken into account. For this purpose, new methods termed shifted
      multivariate spectra analysis (SMSA) and parametric SMSA (pSMSA) are developed
      and tested on sets of synthetic data as well as real experimental amide I'
      spectra for thermal unfolding of an alpha-helical peptide. SMSA uses no specific
      functional form for the transition (soft modeling), while the parametric variant
      (pSMSA) assumes a thermodynamic model (hard modeling). The implementation is
      optimized specifically for amide I' IR in that it takes advantage of known,
      linear dependence of the frequencies as well as intensities on temperature. The
      synthetic data tests demonstrate the robustness of the methods; the initial test
      parameters are recovered with a high degree of reliability, although the
      nonparameteric SMSA is subject to the rotational ambiguity. Application to the
      peptide experimental amide I' data illustrates additional complications
      encountered with the analysis of real systems, such as correction for the side
      chain spectra and interference of spectral shape changes. Nevertheless, the
      results are in excellent agreement with the independent control using circular
      dichroism (CD) data. The general applicability and limitations of the methods are
      discussed along with potential extensions. 

PMID- 24028417
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis in children.

PMID- 24028418
TI  - Full length amylin oligomer aggregation: insights from molecular dynamics
      simulations and implications for design of aggregation inhibitors.
AB  - Amyloid oligomers are considered to play essential roles in the pathogenesis of
      amyloid-related degenerative diseases including type 2 diabetes. Using an
      explicit solvent all atomic MD simulation, we explored the stability,
      conformational dynamics and association force of different single-layer models of
      the full-length wild-type and glycine mutants of amylin (pentamer) obtained from
      a recent high resolution fibril model. The RMSF profile shows enhanced
      flexibility in the disorder (Lys1-Cys7) and turn region (Ser19-Gly23), along with
      smallest fluctuation at the residues (Asn14-Phe15-Leu16-Val17-His18) of beta1
      region and (Ala25-Ile26-Leu27-Ser28-Ser29) of the beta2 region. We obtained a
      significant difference in backbone RMSD between the wild-type and the mutants,
      indicating that mutations affected the stability of the peptide. The RMSD and
      RMSF profiles indicate the edge and loop residues are the primary contributors to
      the overall conformational changes. The degree of structural similarity between
      the oligomers in the simulation and the fibril conformation is proposed as the
      possible explanation for experimentally observed shortening of the nucleation lag
      phase of amylin with oligomer seeding. On the basis of structure-stability
      findings, the beta1 and beta2 portions are optimal target for further anti
      amyloid drug design. The MM-PBSA binding energy calculation reveals the binding
      of amylin: amylin strands in single layer is dominated by contributions from van
      der Waals interactions. The non-polar solvation term is also found to be
      favorable. While the electrostatic interactions and polar solvation energy was
      found to be favorable for the interaction for the larger aggregate and
      unfavorable for the smaller aggregates. A per-residue decomposition of the
      binding free energy has been performed to identify the residues contributing most
      to the self-association free energy. Residues found in the beta-sheet regions
      were found to be key residue making the largest favorable contributions to the
      single-layer association. The result from our simulation could be used in
      rational design of new amylinomimetic agent, amylin aggregation inhibitors and
      amylin-specific biomarkers.

PMID- 24028419
TI  - Myths and misconceptions about tuberculosis transmission in Ghana.
AB  - BACKGROUND: Myths and misconceptions about TB can serve as a barrier to efforts
      at reducing stigmatisation of people infected and affected by the disease.
      Understanding such drivers of myths and misconceptions is important for improving
      information, education and communication (IEC) efforts of national control and
      preventive interventions. This study therefore assesses the influence of
      interaction of spatial, socioeconomic and demographic characteristics on myths
      and misconceptions. METHODS: Data was drawn from male (N = 4,546) and female (N =
      4,916) files of the 2008 Ghana Demographic and Health Survey. A myth and
      misconception variable was created from five-related constructs with internal
      consistency score of r = 0. 8802 for males (inter-item correlation: 0.5951) and
      for females, r = 0. 0.9312 (inter-item correlation: 0.7303). The Pearson Chi
      square was used to test the bivariate relationship between the independent
      variables and the dependent variable. Logistic regression was subsequently used
      to explore the factors determining myths and misconceptions of TB transmission.
      RESULTS: Majority of Ghanaians (males: 66.75%; females: 66.13%) did not hold
      myths and misconceptions about TB transmission. Females resident in the Upper
      East (aOR = 0.31, CI = 0.17-0.55) and Upper West (aOR = 0.41, CI = 0.24-0.69) and
      males resident in the Northern (aOR = 0.23, CI = 0.13-0.39) and the Greater Accra
      (aOR = 0.25, CI = 0.16-0.39) regions were independently associated with no
      misconceptions about TB transmission. Significant differences were also found in
      education, ethnicity and age. CONCLUSION: That spatial and other socioeconomic
      difference exists in myths and misconceptions suggest the need for spatial,
      socioeconomic and demographic segmentations in IEC on TB. This holds potentials
      for reaching out to those who are in critical need of information and education
      on the transmission processes of TB.

PMID- 24028420
TI  - Is chronic pain a disease?

PMID- 24028421
TI  - Isoconversional kinetic analysis of decomposition of nitroimidazoles: Friedman
      method vs Flynn-Wall-Ozawa method.
AB  - We have investigated the decomposition kinetics of imidazole, 2-nitroimidazole,
      and 4-nitroimidazole using TG-DTA technique under nitrogen atmosphere.
      Isoconversional methods were used for the evaluation of kinetic parameters from
      the kinetic data of different heating temperatures. The Friedman method provided
      comparably higher values of activation energy than the Flynn-Wall-Ozawa method.
      Imidazole, 2-nitroimidazole, and 4-nitroimidazole were decomposed by the
      multistep reaction mechanism evident from the nonlinear relationship of
      activation energy and the conversion rate. The NO2 elimination and nitro-nitrite
      isomerization are expected to be competitive reactions in the decomposition of 2
      nitroimidazole and 4-nitroimidazole. The present study may be helpful in
      understanding how the position of NO2 group affects the decomposition kinetics of
      substituted imidazoles. 

PMID- 24028422
TI  - Hierarchically structured manganese oxide-coated magnetic nanocomposites for the
      efficient removal of heavy metal ions from aqueous systems.
AB  - In this study, hierarchical MnO2-coated magnetic nanocomposite (Fe3O4/MnO2) was
      synthesized by a mild hydrothermal process, and its application for removing
      heavy metal ions from contaminated water systems was examined. Structural
      characterization showed that the Fe3O4 nanoparticle core was coated with
      amorphous MnO2 shell with flowerlike morphology. The as-prepared nanocomposite
      had a large surface area and high magnetic saturation value, which ensured its
      good sorption ability and convenience of separation. Fe3O4/MnO2 exhibited a
      greatly improved removal capacity toward four different heavy metals (Cd(II),
      Cu(II), Pb(II), and Zn(II)) compared to unmodified Fe3O4 nanoparticles. The
      adsorption property of Fe3O4/MnO2 was studied with Cd(II) in more detail. The
      sorption equilibrium data were well fitted to the Langmuir model, and the maximum
      adsorption capacity toward Cd(II) was 53.2 mg g(-1). Fe3O4/MnO2 retained over 80%
      of its adsorption capacity under various solution conditions that are typically
      encountered in natural waters. This nanocomposite was easily recovered and reused
      through consecutive adsorption-desorption experiments with the assistance of an
      external magnetic field. Overall, the findings propose that Fe3O4/MnO2 could be
      used as an effective recyclable adsorbent for heavy metal ions. 

PMID- 24028425
TI  - First steps in growth of a polypeptide toward beta-sheet structure.
AB  - The full conformational energy surface is examined for a molecule in which a
      dipeptide is attached to the same spacer group as another peptide chain, so as to
      model the seminal steps of beta-sheet formation. This surface is compared with
      the geometrical preferences of the isolated dipeptide to extract the
      perturbations induced by interactions with the second peptide strand. These
      interpeptide interactions remove any tendency of the dipeptide to form a C5 ring
      structure, one of its two normally stable geometries. A C7 structure, the
      preferred conformation of the isolated dipeptide, remains as the global minimum
      in the full molecule. However, the stability of this structure is highly
      dependent upon interpeptide H-bonds with the second chain. The latter forces
      include not only the usual NH...O interaction, but also a pair of CH...O H-bonds.
      The secondary minimum is also of C7 type and likewise depends in part upon CH...O
      H-bonds for its stability. The latter interactions also play a part in the
      tertiary minimum. A two-strand beta-sheet structure is not yet in evidence for
      this small model system, requiring additional peptide units to be added to each
      chain. 

PMID- 24028424
TI  - Mechanism and enantioselectivity in palladium-catalyzed conjugate addition of
      arylboronic acids to beta-substituted cyclic enones: insights from computation
      and experiment.
AB  - Enantioselective conjugate additions of arylboronic acids to beta-substituted
      cyclic enones have been previously reported from our laboratories. Air- and
      moisture-tolerant conditions were achieved with a catalyst derived in situ from
      palladium(II) trifluoroacetate and the chiral ligand (S)-t-BuPyOx. We now report
      a combined experimental and computational investigation on the mechanism, the
      nature of the active catalyst, the origins of the enantioselectivity, and the
      stereoelectronic effects of the ligand and the substrates of this transformation.
      Enantioselectivity is controlled primarily by steric repulsions between the t-Bu
      group of the chiral ligand and the alpha-methylene hydrogens of the enone
      substrate in the enantiodetermining carbopalladation step. Computations indicate
      that the reaction occurs via formation of a cationic arylpalladium(II) species,
      and subsequent carbopalladation of the enone olefin forms the key carbon-carbon
      bond. Studies of nonlinear effects and stoichiometric and catalytic reactions of
      isolated (PyOx)Pd(Ph)I complexes show that a monomeric arylpalladium-ligand
      complex is the active species in the selectivity-determining step. The addition
      of water and ammonium hexafluorophosphate synergistically increases the rate of
      the reaction, corroborating the hypothesis that a cationic palladium species is
      involved in the reaction pathway. These additives also allow the reaction to be
      performed at 40  degrees C and facilitate an expanded substrate scope. 

PMID- 24028426
TI  - Correlation between the area of high-signal intensity on SPIO-enhanced MR imaging
      and the pathologic size of sentinel node metastases in breast cancer patients
      with positive sentinel nodes.
AB  - BACKGROUND: We previously demonstrated that superparamagnetic iron oxide (SPIO)
      enhanced MR imaging is promising for the detection of metastases in sentinel
      nodes localized by CT-lymphography in patients with breast cancer. The purpose of
      this study was to determine the predictive criteria of the size of nodal
      metastases with SPIO-enhanced MR imaging in breast cancer, with histopathologic
      findings as reference standard. METHODS: This study included 150 patients with
      breast cancer. The patterns of SPIO uptake for positive sentinel nodes were
      classified into three; uniform high-signal intensity, partial high-signal
      intensity involving >=50% of the node, and partial high-signal intensity
      involving <50% of the node. Imaging results were correlated with histopathologic
      findings. RESULTS: Thirty-three pathologically positive sentinel nodes from 30
      patients were evaluated. High-signal intensity patterns that were uniform or
      involved >=50% of the node were observed in 23 nodes that contained macro
      metastases and no node that contained micro-metastases, while high-signal
      intensity patterns involving <50% of the node were observed in 2 nodes that
      contained macro-metastases and 8 nodes that contained micro-metastases. When the
      area of high-signal intensity was compared with the pathological size of the
      metastases, a pathologic >2 mm sentinel node metastases correlated with the area
      of high-signal intensity, however, a pathologic <=2 mm sentinel node metastases
      did not. CONCLUSIONS: High-signal intensity patterns that are uniform or involve
      >=50% of the node are features of nodes with macro-metastases. The area of high
      signal intensity correlated with the pathological size of metastases for nodes
      with metastases >2 mm in this series.

PMID- 24028427
TI  - Caffeic acid phenethyl ester (CAPE) protects against acute urogenital injury
      following pneumoperitoneum in the rat.
AB  - PURPOSE: Our aim is to determine the biochemical and histologic changes induced
      in the kidneys, testis and prostate on possible ischemia and reperfusion (I/R)
      injury caused by pneumoperitoneum (PNP) in a rat model and to evaluate the
      ability of protective effects of caffeic acid phenethyl ester (CAPE). METHODS:
      Twenty-eight adult male Wistar albino rats were randomly divided to one of three
      treatment groups, with seven animals in each group. Sham, laparoscopy (L), and
      laparoscopy plus CAPE (L + C) group were subjected to 60 min of PNP with 15 mmHg
      one hour before the desufflation period. Total oxidant status (TOS) and total
      antioxidant status (TAS) levels were determined in kidney, testis, and prostate.
      Kidney and testis tissues were removed to obtain a histologic score. Also,
      Johnsen scoring system was used for testicular tissue analysis. RESULTS: L group
      had significantly higher TOS and lower TAS levels on kidney and testis compared
      to the other groups. In prostate biochemical analysis, there was not any
      difference between groups. No difference was found between groups according to
      kidney and testis tissues' histologic evaluation. In evaluation of Johnsen
      scoring, L group showed significant lower score compared to the other two groups.
      CONCLUSIONS: Increased intraabdominal pressure (IAP) had an oxidative effect on
      kidney and testis but not on prostate in rats. Moreover, it could affect the
      testicular Johnsen score. All these adverse effects of IAP on both kidney and
      testis could be prevented by CAPE administration.

PMID- 24028429
TI  - The role of practical wisdom in nurse manager practice: why experience matters.
AB  - AIM: To illustrate through the interpretation of one representative nurse
      manager's narrative how the methodology of practice articulation gives language
      to the ways practical wisdom develops in leadership practice and facilitates
      learning. BACKGROUND: Patricia Benner's corpus of research has demonstrated that
      reflection on clinical narratives comes closer than other pedagogical methods to
      replicating and enhancing the experiential learning required for the development
      of practical wisdom. METHOD: Using Benner's methodology of practice articulation,
      91 nurse managers wrote and read to a peer group a narrative of their lived
      experience in the role. The groups interpreted the narratives to extract the
      skilled knowledge and ethics embedded in the practice of the nurse manager
      authors. One narrative was chosen for this paper because it is a particularly
      clear exemplar of how practical wisdom develops in nurse manager practice.
      RESULTS: Articulating and reflecting on experiential learning led to an
      understanding of how practical wisdom developed in one nurse manager's practice.
      CONCLUSION: Interpretation of the narrative of one nurse manager illustrated how
      reflection on a complex ethical dilemma was a source of character development for
      the individual and the peer group. IMPLICATIONS FOR NURSING MANAGEMENT:
      Describing and interpreting how practical wisdom develops for individual nurse
      managers can be a source of learning for the narrative author and other role
      incumbents who need to make sound decisions and take prudent action in ethically
      challenging situations.

PMID- 24028428
TI  - A comparative study of the dentate gyrus in hippocampal sclerosis in epilepsy and
      dementia.
AB  - AIMS: Hippocampal sclerosis (HS) is long-recognized in association with epilepsy
      (HSE ) and more recently in the context of cognitive decline or dementia in the
      elderly (HSD ), in some cases as a component of neurodegenerative diseases,
      including Alzheimer's disease (AD) and fronto-temporal lobe dementia (FTLD).
      There is an increased risk of seizures in AD and spontaneous epileptiform
      discharges in the dentate gyrus of transgenic AD models; epilepsy can be
      associated with an age-accelerated increase in AD-type pathology and cognitive
      decline. The convergence between these disease processes could be related to
      hippocampal pathology. HSE typically shows re-organization of both excitatory and
      inhibitory neuronal networks in the dentate gyrus, and is considered to be
      relevant to hippocampal excitability. We sought to compare the pathology of HSE
      and HSD , focusing on re-organization in the dentate gyrus. METHODS: In nine post
      mortem cases with HSE and bilateral damage, 18 HSD and 11 controls we carried out
      immunostaining for mossy fibres (dynorphin), and interneuronal networks (NPY,
      calbindin and calretinin) on sections from the mid-hippocampal body. Fibre
      sprouting (FS) or loss of expression in the dentate gyrus was semi-quantitatively
      graded from grade 0 (normal) to grade 3 (marked alteration). RESULTS:
      Significantly more re-organization was seen with all four markers in the HSE than
      HSD group (P < 0.01). Mild alterations were noted in HSD group with dynorphin (FS
      in 3 cases), calretinin (FS in 6 cases), NPY (FS in 11 cases) and calbindin (loss
      in 10 cases). In eight HSD cases, alteration was seen with more than one antibody
      but in no cases were the highest grades seen. We also noted NPY and, to a lesser
      extent, calretinin labelling of Hirano bodies in CA1 of AD cases and some older
      controls, but not in HSE . CONCLUSION: Reorganization of excitatory and
      inhibitory networks in the dentate gyrus is more typical of HSE . Subtle
      alterations in HSD may be a result of increased hippocampal excitability,
      including unrecognized seizure activity. An unexpected finding was the
      identification of NPY-positive Hirano bodies in HSD but not HSE , which may be a
      consequence of the relative vulnerabilities of interneurons in these conditions.

PMID- 24028431
TI  - Accuracy of sonographic prediction of birth weight.
AB  - Many clinicians use ultrasound estimates of fetal weight to assess fetal growth.
      This study assessed the accuracy of the Hadlock IV equation, the equation used at
      the Royal Hospital for Women, Randwick, NSW, in estimating birth weight. The
      accuracy of the Hadlock IV equation was assessed based on systematic and random
      error as well as absolute error. 709 women who underwent ultrasound examination
      within 8 weeks of delivery between January 2009-May 2011 were included. 305 women
      underwent ultrasound less than 2 weeks before delivery. The systematic, random
      and absolute errors of the Hadlock IV equation were -0.47, 27.45 and 8.52%,
      respectively. This study demonstrates that clinicians may rely on ultrasound
      estimates of fetal weight performed by well-trained staff in a tertiary
      institution within 2 weeks of delivery. The accuracy diminishes as the interval
      between testing and delivery increases. Absolute errors tended to increase with
      increasing birth weight for all ultrasound-delivery intervals. 

PMID- 24028432
TI  - Antimicrobial dressing efficacy against mature Pseudomonas aeruginosa biofilm on
      porcine skin explants.
AB  - An ex vivo porcine skin explant biofilm model that preserves key properties of
      biofilm attached to skin at different levels of maturity (0-3 days) was used to
      assess the efficacy of commercially available antimicrobial dressings and topical
      treatments. Assays were also performed on the subpopulation of antibiotic
      tolerant biofilm generated by 24 hours of pre-treatment with gentamicin (120*
      minimal inhibitory concentration) prior to agent exposure. Five types of
      antimicrobial agents (iodine, silver, polyhexamethylene biguanide, honey and
      ethanol) and four types of moisture dressings (cotton gauze, sodium
      carboxymethylcellulose fibre, calcium alginate fibre and cadexomer beads) were
      assessed. Time-release silver gel and cadexomer iodine dressings were the most
      effective in reducing mature biofilm [between 5 and 7 logarithmic (log) of 7-log
      total], whereas all other dressing formulations reduced biofilm between 0.3 and 2
      log in 24 or 72 hours with a single exposure. Similar results were found after 24
      hour exposure to silver release dressings using an in vivo pig burn wound model,
      demonstrating correlation between the ex vivo and in vivo models. Results of this
      study indicate that commonly used microbicidal wound dressings vary widely in
      their ability to kill mature biofilm and the efficacy is influenced by time of
      exposure, number of applications, moisture level and agent formulation (sustained
      release). 

PMID- 24028433
TI  - Real-time NMR monitoring of protein-folding kinetics by a recycle flow system for
      temperature jump.
AB  - An NMR method was developed that allows for real-time monitoring of reactions (on
      the order of seconds) induced by a temperature jump. In a recycle flow system,
      heating and cooling baths were integrated, with the latter inside the NMR probe.
      A refolding reaction of ribonuclease A was triggered by rapid cooling and
      monitored by a series of NMR measurements over 12 s. Data were processed by
      principal component analysis, in which a factor related to the structural change
      with an exponential rate constant of 0.2-0.7 s(-1) was successfully separated
      from factors related to baseline instability and/or noise. Temperature dependency
      of the rate constant revealed the entropy-driven formation of the transition
      state of the refolding reaction. 

PMID- 24028434
TI  - The contribution of an avian top predator to selection in prey species.
AB  - Natural selection can vary in magnitude, form and direction, yet the causes of
      selection, and of variation in selection, are poorly understood. We quantified
      the effect of a key predator (Eurasian sparrowhawks) on selection on fledging
      body mass in two bird species (blue tits and great tits). By partitioning
      selection into within- and between-brood components, we were able to separate
      individual from brood-level effects of fledging mass on predation probability and
      recruitment. In blue tits, selection on fledging mass by sparrowhawk predation
      was nonsignificant and could not explain selection to recruitment. In contrast,
      in great tits, sparrowhawk predation selected for increased fledging mass at the
      individual level and could explain 73% of individual-level selection on fledging
      mass to recruitment. Moreover, in great tits, individual-level selection on
      fledging mass was significantly stronger in years in which sparrowhawks were
      present compared to years when sparrowhawks were absent. Selection at the brood
      level was independent of sparrowhawk presence. These results provide compelling
      evidence that sparrowhawk predation acts as an important causal agent of
      selection on fledging mass in great tits but not in blue tits. Variation in
      predation pressure can therefore account for variation in selection, but specific
      patterns may not be easily generalized across species.

PMID- 24028435
TI  - Development of the scale of psychosocial factors in food allergy (SPS-FA).
AB  - BACKGROUND: Food allergy (FA) is a growing condition among children and it's
      psychological impact over the patients and their caregivers is well known,
      establishing a vicious circle that perpetuates stress levels. However,
      psychosocial factors are not commonly included in allergy treatments. Based on
      the lack of evidence of records about a scale that indicates the level of
      interaction between biopsychosocial factors in the patient-caregivers dyad for
      FA, the present research aims to develop a scale with these characteristics as a
      helpful tool to achieve a more comprehensive system of health care. METHODS: A
      preliminary 28-item scale was generated (sample N = 99). The scale was adjusted
      in contents and language after expert opinion and application on patients. A
      factor analysis was carried out selecting the items from the final scale.
      RESULTS: The final 9-item scale included three areas: impact on quality of life,
      social impact and conflicts. The scale had a good internal consistency
      (Cronbach's alpha = 0.870) and correlated significantly with anxiety and
      depression measurements. Moreover, it was able to discriminate between study
      groups (members and non-members of peer support groups) and proved construct
      validity. CONCLUSIONS: The SPS-FA is the first scale for the assessment of the
      interaction of biopsychosocial factors on FA that includes the patient-caregiver
      dyad. Its application might be relevant for future research, and it can provide
      the clinician and the researcher with a solid tool to define which type of
      psychosocial support is required to provide a more comprehensive care in FA.

PMID- 24028436
TI  - Obesity can influence children's and adolescents' airway hyperresponsiveness
      differently.
AB  - BACKGROUND: Literature is still arguing about a possible relationship between
      airway hyperresponsiveness (AHR) and body mass index (BMI). This study aimed at
      evaluating the influence of BMI on AHR and pulmonary function in children and
      adolescents that performed a methacholine test for suggestive asthma symptoms.
      METHODS: 799 consecutive children/adolescents (535 M; mean age: 15 +/- 3 yrs;
      median FEV1% predicted: 101.94% [93.46-111.95] and FEV1/FVC predicted: 91.07
      [86.17-95.38]), were considered and divided into underweight, normal, overweight
      and obese. Different AHR levels were considered as moderate/severe (PD20 <= 400
      MUg) and borderline (PD20 > 400 MUg). RESULTS: 536 children/adolescents resulted
      hyperreactive with a median PD20 of 366 MUg [IQR:168-1010.5]; 317 patients were
      affected by moderate/severe AHR, whereas 219 showed borderline
      hyperresponsiveness. Obese subjects aged > 13 years showed a lower (p = 0.026)
      median PD20 (187MUg [IQR:110-519]) compared to overweight (377 MUg [IQR:204-774])
      and normal-weight individuals' values (370.5 MUg [IQR:189-877]). On the contrary,
      median PD20 observed in obese children aged <= 13 years (761 MUg [IQR:731-1212])
      was higher (p = 0.052) compared to normal-weight children's PD20 (193 MUg [IQR:81
      542]) and to obese adolescents' values (aged > 13 years) (p = 0.019). Obesity was
      a significant AHR risk factor (OR:2.853[1.037-7.855]; p = 0.042) in
      moderate/severe AHR adolescents. Females showed a higher AHR risk (OR:1.696[1.046
      2.751] p = 0.032) compared to males. A significant relationship was found between
      BMI and functional parameters (FEV1, FVC, FEV1/FVC) only in hyperreactive
      females. CONCLUSIONS: Obesity seems to influence AHR negatively in female but not
      in male adolescents and children. In fact, AHR is higher in obese teenagers, in
      particular in those with moderate/severe hyperresponsiveness, and may be mediated
      by obesity-associated changes in baseline lung function.

PMID- 24028437
TI  - Blockage of Nrf2 suppresses the migration and invasion of esophageal squamous
      cell carcinoma cells in hypoxic microenvironment.
AB  - Nuclear factor erythroid-2-related factor 2 (Nrf2) is a critical cell protector
      by inducing phase two detoxifying and anti-oxidant enzymes in normal cells. But
      recently, numerous evidence show Nrf2 may play the same beneficial roles toward
      the cancer cells. Nrf2 is found upexpressed in lots of cancers and promote the
      proliferation and drug resistance. But studies about the role of Nrf2 in the
      metastases are few. It has been testified that the tumor cells are under hypoxic
      conditions. As an important anti-oxidant element, the expression of Nrf2 may be
      upregulated, which in turn promotes the tumor invasion and metastases in the
      hypoxic microenvironment. Our team found the expression of Nrf2 correlated with
      the lymph node metastasis of esophageal squamous cell carcinoma by pathological
      sections of esophageal carcinoma patients. Further, the mechanism beneath it was
      studied in this paper. It was hypothesized that the hypoxia microenvironment
      transformed Nrf2 a friend to a foe. First, Eca-109 cells were treated with
      different concentration of CoCl2 . Western blot and quantitative reverse
      transcription-polymerase chain reaction showed that with the increase of the
      concentration of CoCl2 , the expression levels of Nrf2 and hypoxia-inducible
      factor-1 (HIF-1) alpha were upregulated simultaneously. By analyzing the data, a
      significant correlation between Nrf2 and HIF-1 alpha in the protein levels was
      found. Further, blockage of Nrf2 mediated by shRNA suppressed the expression of
      HIF-1 alpha, hemeoxygenase-1 (HO-1), and matrix metalloproteinase 2 but enhanced
      the expression of E-cadherin. In addition, the results of wound healing and
      invasion assay-verified blockage of Nrf2 suppressed the migration and invasion.
      So it was suggested that blockage of Nrf2 repressed the migration and invasion of
      esophageal squamous cell carcinoma cells in the hypoxic microenvironment. HIF-1
      alpha might be one of the downstream genes of Nrf2 regulated through Nrf2/HO-1
      axis in the CoCl2 model. Nrf2 inhibition suppressed matrix metalloproteinase 2
      and enhanced E-cadherin partly through HIF-1 alpha way. 

PMID- 24028438
TI  - The importance of echocardiography in transcatheter aortic valve implantation.
AB  - Valvular heart diseases cause serious health problems in Turkey as well as in
      Western countries. According to a study conducted in Turkey, aortic stenosis (AS)
      is second after mitral valve disease among all valvular heart diseases. AS is
      frequently observed in elderly patients who have several cardiovascular risk
      factors and comorbidities. In symptomatic severe AS, surgical aortic valve
      replacement (AVR) is a definitive treatment. However, in elderly patients with
      left ventricular dysfunction and comorbidities, the risk of operative morbidity
      and mortality increases and outweighs the gain obtained from AVR surgery. As a
      result, almost one-third of the patients with serious AS are considered
      ineligible for surgery. Transcatheter aortic valve implantation (TAVI) is an
      effective treatment in patients with symptomatic severe AS who have high risk for
      conventional surgery. Since being performed for the first time in 2002, with a
      procedure success rate reported as 95% and a mortality rate of 5%, TAVI has
      become a promising method. Assessment of vascular anatomy, aortic annular
      diameter, and left ventricular function may be useful for the appropriate
      selection of patients and may reduce the risk of complications. Cardiac imaging
      methods including 2D and 3D echocardiography and multidetector computed
      tomography are critical during the evaluation of suitable patients for TAVI as
      well as during and after the procedure. In this review, we describe the role of
      echocardiography methods in clinical practice for TAVI procedure in its entirety,
      i.e. from patient selection to guidance during the procedure, and subsequent
      monitoring. 

PMID- 24028439
TI  - Soldier occupational load carriage: a narrative review of associated injuries.
AB  - This narrative review examines injuries sustained by soldiers undertaking
      occupational load carriage tasks. Military soldiers are required to carry
      increasingly heavier occupational loads. These loads have been found to increase
      the physiological cost to the soldier and alter their gait mechanics. Aggregated
      research findings suggest that the lower limbs are the most frequent anatomical
      site of injury associated with load carriage. While foot blisters are common,
      other prevalent lower limb injuries include stress fractures, knee and foot pain,
      and neuropathies, like digitalgia and meralgia. Shoulder neuropathies (brachial
      plexus palsy) and lower back injuries are not uncommon. Soldier occupational load
      carriage has the potential to cause injuries that impact on force generation and
      force sustainment. Through understanding the nature of these injuries targeted
      interventions, like improved physical conditioning and support to specialised
      organisations, can be employed. 

PMID- 24028440
TI  - Structure-wise discrimination of cytosine, thymine, and uracil by proteins in
      terms of their nonbonded interactions.
AB  - The molecular recognition and discrimination of very similar ligand moieties by
      proteins are important subjects in protein-ligand interaction studies.
      Specificity in the recognition of molecules is determined by the arrangement of
      protein and ligand atoms in space. The three pyrimidine bases, viz. cytosine,
      thymine, and uracil, are structurally similar, but the proteins that bind to them
      are able to discriminate them and form interactions. Since nonbonded interactions
      are responsible for molecular recognition processes in biological systems, our
      work attempts to understand some of the underlying principles of such recognition
      of pyrimidine molecular structures by proteins. The preferences of the amino acid
      residues to contact the pyrimidine bases in terms of nonbonded interactions;
      amino acid residue-ligand atom preferences; main chain and side chain atom
      contributions of amino acid residues; and solvent-accessible surface area of
      ligand atoms when forming complexes are analyzed. Our analysis shows that the
      amino acid residues, tyrosine and phenyl alanine, are highly involved in the
      pyrimidine interactions. Arginine prefers contacts with the cytosine base. The
      similarities and differences that exist between the interactions of the amino
      acid residues with each of the three pyrimidine base atoms in our analysis
      provide insights that can be exploited in designing specific inhibitors
      competitive to the ligands.

PMID- 24028441
TI  - Postoperative pain and perioperative outcomes after laparoscopic radical
      hysterectomy and abdominal radical hysterectomy in patients with early cervical
      cancer: a randomised controlled trial.
AB  - BACKGROUND: Non-randomised studies have suggested that the postoperative
      complications of (Campos LS, Limberger LF, Stein AT, Kalil AN) laparoscopic
      radical hysterectomy are similar to those in abdominal radical hysterectomy.
      However, no study evaluating postoperative pain comparing both techniques has
      been published thus far. Our objective was to compare pain intensity and other
      perioperative outcomes between laparoscopic radical hysterectomy (LRH) and
      abdominal radical hysterectomy (ARH) in early cervical cancer. METHODS: This
      single centre, randomised, controlled trial enrolled 30 cervical cancer patients
      who were clinically staged IA2 with lymph vascular invasion and IB according to
      the FIGO (International Federation of Gynaecology and Obstetrics) classification,
      and underwent LRH or ARH between late 1999 and early 2004. Postoperative pain, as
      measured by a 10-point numerical rate scale, was considered the primary endpoint.
      Postoperative pain was assessed every six hours during a patient's usual
      postoperative care. Perioperative outcomes were also registered. Both surgical
      techniques were executed by the same surgical team. Secondary outcomes included
      intraoperative and other postoperative surgicopathological factors and 5-year
      survival rates. RESULTS: IA2 patients with lymphatic vascular space invasion and
      IB cervical cancer patients were randomised to either the LRH group (16 patients)
      or the ARH group (14 patients). Four patients (25%) in the LRH group and 5
      patients (36%) in the ARH group presented with transoperative or serious
      postoperative complications. All of the transoperative complications occurred in
      the LRH group. The relative risk of presenting with complications was 0.70; CI
      95% (0.23-2.11); P = 0.694. LRH group mean pain score was significantly lower
      than ARH after 36 h of observation (P = 0.044; mean difference score: 1.42; 95%
      CI: 0.04-2.80). The survival results will be published elsewhere. CONCLUSIONS:
      LRH provided lower pain scores after 36 h of observation in this series. The
      perioperative and serious postoperative complications ratios were comparable
      between the groups. TRIAL REGISTRATION: NCT01258413.

PMID- 24028442
TI  - Early neuroendocrine disruption in hypothalamus and hippocampus: developmental
      effects including female sexual maturation and implications for endocrine
      disrupting chemical screening.
AB  - The timing of puberty has been mainly studied in females for several reasons,
      including the possible evaluation of a precise timer (i.e. menarcheal age) and
      concerns with respect to the high prevalence of precocity in females as opposed
      to males. Human evidence of altered female pubertal timing after exposure to
      endocrine disrupting chemicals (EDCs) is equivocal. Among the limiting factors,
      most studies evaluate exposure to single EDCs at the time of puberty and hardly
      assess the impact of lifelong exposure to mixtures of EDCs. Some rodent and ovine
      studies indicate a possible role of foetal and neonatal exposure to EDCs, in
      accordance with the concept of an early origin of health and disease. Such
      effects possibly involve neuroendocrine mechanisms because the hypothalamus is a
      site where homeostasis of reproduction, as well as control of energy balance, is
      programmed and regulated. In our previous studies, pulsatile gonadotrophin
      releasing hormone (GnRH) secretion control via oestrogen, glutamate and aryl
      hydrocarbon receptors was shown to be involved in the mechanism of sexual
      precocity after early postnatal exposure to the insecticide
      dichlorodiphenyltrichloroethane. Very recently, we have shown that neonatal
      exposure to the potent synthetic oestrogen diethylstilbestrol (DES) is followed
      by early or delayed puberty depending on the dose, with consistent changes in
      developmental increase of GnRH pulse frequency. Moreover, DES results in reduced
      leptin stimulation of GnRH secretion in vitro, an effect that is additive with
      prenatal food restriction. Thus, using puberty as an endpoint of the effects of
      EDC, it appears necessary to consider pre- and perinatal exposure to low doses
      and to pay attention to the other conditions of prenatal life, such as energy
      availability, keeping in mind the possibility that puberty could not only be
      advanced, but also delayed through neuroendocrine mechanisms. 

PMID- 24028443
TI  - Nonvolatile flash memory based on biologically integrated hierarchical
      nanostructures.
AB  - The first six peptides of multifunctional titanium binding peptide-1 bestowed
      recombinant L-ferritin, minT1-LF, was genetically engineered and used to
      fabricate multilayered nanoparticle architecture. The multifunctionality of minT1
      LF enables specific binding of nanoparticle-accommodated minT1-LF to the silicon
      substrate surface and wet biochemical fabrication of gate oxide layer by its
      biomineralization activity. Three-dimensional (3D) nanoparticle architecture with
      multilayered structure was fabricated by the biological layer-by-layer method and
      embedded in a metal oxide-semiconductor device structure as a charge storage node
      of a flash memory device. The 3D-integrated multilayered nanoparticle
      architecture successfully worked as a charge storage node in flash memory devices
      that exhibited improved charge storage capacity compared with that of a
      conventional monolayer structure device. 

PMID- 24028444
TI  - Primary vs secondary prophylaxis with pegfilgrastim for the reduction of febrile
      neutropenia risk in patients receiving chemotherapy for non-Hodgkin's lymphoma:
      cost-effectiveness analyses.
AB  - OBJECTIVE: Evaluate the cost-effectiveness of primary vs secondary prophylaxis
      (PP vs SP) with pegfilgrastim to reduce the risk of febrile neutropenia (FN) in
      Non-Hodgkin's Lymphoma (NHL) patients receiving myelosuppressive chemotherapy
      from a US payer perspective. METHODS: A Markov model was used to compare PP vs SP
      with pegfilgrastim in a cohort of patients receiving six cycles of
      cyclophosphamide, vincristine, doxorubicin, and prednisone (CHOP) or CHOP plus
      rituximab (CHOP-R) chemotherapy. Model inputs, including efficacy of
      pegfilgrastim in reducing risk of FN and costs, were estimated from publicly
      available sources and peer-reviewed publications. Incremental cost-effectiveness
      was evaluated in terms of net cost per life-year saved (LYS), per quality
      adjusted life-year (QALY) gained, and per FN event avoided over a lifetime
      horizon. Deterministic and probabilistic analyses were performed to assess
      sensitivity and robustness of results. RESULTS: Lifetime costs for PP were $5000
      greater than for SP; however, PP was associated with fewer FN events and more LYs
      and QALYs gained vs SP. Incremental cost-effectiveness ratios (ICERs) for PP vs
      SP for CHOP were $13,400 per FN event avoided, $29,500 per QALY gained, and
      $25,800 per LYS. CHOP-R results were similar ($15,000 per FN event avoided,
      $33,000 per QALY gained, and $28,900 per LYS). Results were most sensitive to
      baseline FN risk, cost per FN episode, and odds ratio for reduced relative dose
      intensity due to prior FN event. PP was cost-effective vs SP in 85% of
      simulations at a $50,000 per QALY threshold. LIMITATIONS: In the absence of NHL
      specific data, estimates for pegfilgrastim efficacy and relative risk reduction
      of FN were based on available data for neoadjuvant TAC in patients with breast
      cancer. Baseline risks of FN for CHOP and CHOP-R were assumed to be equivalent.
      CONCLUSIONS: PP with pegfilgrastim is cost-effective compared to SP with
      pegfilgrastim in NHL patients receiving CHOP or CHOP-R.

PMID- 24028445
TI  - Effect of hyperprolactinaemia on intra-ocular pressure.

PMID- 24028446
TI  - Novel peptide-doxorubucin conjugates for targeting breast cancer cells including
      the multidrug resistant cells.
AB  - The efficacy of chemotherapeutic doxorubucin (Dox) in cancer treatment is limited
      by two main factors, nonspecific toxicity and the emergence of tumor resistance.
      To overcome these hurdles, in this study peptide-Dox conjugates were prepared. A
      decapeptide 18-4a (NH2-WxEAAYQkFL-CONH2) [corrected] with high specificity for
      breast cancer cells and improved proteolytic stability was conjugated to Dox to
      give peptide-Dox ester (1) and amide (2) conjugates. Cell uptake studies showed
      that the conjugates were 6-10 times selective for breast cancerous cells (MCF-7
      and MDA-MB-435) over noncancerous cells (HUVECs and MCF-10A). Conjugate 1
      displayed similar toxicity as free Dox toward the breast cancerous cells and was
      about 40 times less toxic toward the noncancerous cells and 4-fold more toxic
      toward the Dox resistant MDA-MB-435-MDR cells than the free Dox. These data
      suggest that conjugate 1 can be used as a potential prodrug for improving the
      therapeutic index of Dox and potentially many other cytotoxic drugs.

PMID- 24028447
TI  - Repair of cartilage defects in arthritic tissue with differentiated human
      embryonic stem cells.
AB  - Chondrocytes have been generated in vitro from a range of progenitor cell types
      and by a number of strategies. However, achieving reconstitution of actual
      physiologically relevant, appropriately-laminated cartilage in situ that would be
      applicable to conditions, such as arthritis and cartilage degeneration remains
      elusive. This lack of success is multifactorial and includes limited cell source,
      decreased proliferation rate of mature chondrocytes, lack of maintenance of
      phenotype, reduced matrix synthesis, and poor integration with host tissue. We
      report an efficient approach for deriving mesenchymal chondroprogenitor cells
      from human embryonic stem cells. These cells generated tissue containing
      cartilage-specific matrix proteins that integrated in situ in a partial-thickness
      defect in ex vivo articular cartilage harvested from human arthritic joints.
      Given that stem cells provide a virtually inexhaustible supply of starting
      material and that our technique is easily scalable, cartilaginous tissue primed
      and grafted in this manner could be suitable for clinical translation. 

PMID- 24028449
TI  - Excited electronic state mixing in 7-azaindole. Quantitative measurements using
      the Stark effect.
AB  - Stark effect measurements of the +280 cm(-1) vibronic band at ~286 nm in the high
      resolution S1-S0 fluorescence excitation spectrum of 7-azaindole (7AI) in a
      molecular beam show that the permanent (electric) dipole moment (PDM) of the
      upper state vibrational level reached in this transition is 4.6 D, twice as large
      as the PDM of the zero-point level of the S1 state. This large difference is
      attributed to state mixing with a more polar state. EOM-CSSD calculations suggest
      that this more polar state is sigmapi* in nature and that it crosses the pipi*
      state in energy along the coordinate connecting the two potential energy minima.
      Such state mixing apparently provides more facile access to conical intersections
      with the ground state, and subsequent hydrogen atom detachment reactions, since
      independent studies by Sakota and Sekiya have shown that the N-H stretching
      frequency of 7AI is significantly reduced when it is excited to the +280 cm(-1)
      vibrational level of the S1 state. 

PMID- 24028448
TI  - Association between aldehyde dehydrogenase 2 polymorphisms and the incidence of
      diabetic retinopathy among Japanese subjects with type 2 diabetes mellitus.
AB  - BACKGROUND: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies reactive
      aldehydes in the micro- and macrovasculature. These substrates, including
      methylglyoxal and 4-hydroxynonenal formed from glucose and lipids, cause protein
      carbonylation and mitochondrial dysfunction, forming advanced glycation end
      products (AGEs). The present study aimed to confirm the association between the
      inactive ALDH2*2 allele and diabetic retinopathy (DR). METHODS: A retrospective
      longitudinal analysis was conducted, among 234 Japanese patients with type 2
      diabetes mellitus (DM) (156 males and 78 females) who had no DR signs at baseline
      and were treated for more than half a year. The ALDH2*1/*2 alleles were
      determined using a real-time TaqMan allelic discrimination assay. Multivariate
      adjusted hazard ratios (HRs) and 95% confidential intervals (CIs) for the
      cumulative incidence of the development of DR were examined using a Cox
      proportional hazard model, taking drinking habits and the serum gamma
      glutamyltransferase (GGT) level into consideration. RESULTS: The frequency of the
      ALDH2*2 allele was 22.3%. Fifty-two subjects cumulatively developed DR during the
      follow-up period of 5.5 +/- 2.5 years. The ALDH2*2 allele carriers had a
      significantly higher incidence of DR than the non-carriers (HR: 1.92; P = 0.02).
      The incidence of DR was significantly higher in the drinkers with the ALDH2*2
      allele than in those with the ALDH2*1/*1 genotype (HR: 2.61; P = 0.03), while the
      incidence of DR in the non-drinkers did not differ significantly between the
      ALDH2 genotype groups (P > 0.05). The incidence of DR was significantly higher in
      the ALDH2*2 allele carriers with a high GGT level than in the non-carriers with a
      high or low GGT level (HR: 2.45; P = 0.03; and HR: 2.63; P = 0.03, respectively).
      CONCLUSIONS: To the best of our knowledge, this is the first report of a
      significant association between the ALDH2*2 allele and the incidence of DR. These
      findings provide additional evidence that ALDH2 protects both microvasculature
      and macrovasculature against reactive aldehydes generated under conditions of
      sustained oxidative stress, although further investigations in larger cohorts are
      needed to verify the results.

PMID- 24028450
TI  - Crystal structure, phase transitions, and magnetic properties of iridium
      perovskites Sr2MIrO6 (M = Ni, Zn).
AB  - Double perovskites containing Ir(6+)/Ir(5+) with formula Sr2MIrO6 (M = Ni, Zn)
      have been synthesized under high oxygen pressure conditions. Their crystal
      structures have been studied by X-ray and neutron powder diffraction at room
      temperature (RT) and 2 K. At RT, these oxides crystallize in the monoclinic space
      group P2(1)/n with unit-cell parameters a ~ ?2a0, b ~ ?2a0, and c ~ 2a0, and beta
      ~ 90 degrees . The thermal evolution of the structure of the Ni-containing
      compound shows the presence of two phase transition in the 373-673 K interval
      following the sequence P2(1)/n -> I4/m -> Fm3m. These materials have also been
      characterized by magnetic measurements, suggesting the onset of antiferromagnetic
      interactions at T(N) = 58 and 46 K, for M = Ni, Zn, respectively. X-ray
      absorption spectroscopy sheds light on the oxidation states of M and Ir ions
      within these double perovskites.

PMID- 24028451
TI  - Atmospheric significance of water clusters and ozone-water complexes.
AB  - Ozone-water complexes O3...(H2O)n (n = 1-4) have been theoretically investigated
      using QCISD and CCSD(T) methods along with the 6-311G(2df,2p), 6-311+G(2df,2p),
      aug-cc-pVDZ, aug-cc-pVTZ, and aug-cc-pVQZ basis sets and extrapolation to CBS
      limit. For comparison, water clusters (H2O)n (n = 1-4) have also been studied at
      the same level of theory. The ozone-water complexes are held together by a
      combination of weak specific hydrogen-bonding and van der Waals interactions.
      Surprisingly, the hydrogen-bonded complexes are not necessarily the most stable
      ones. In particular, in the most stable 1:1 complex structure the main
      stabilizing factors come from van der Waals interactions. The high accuracy of
      the calculated binding energies provides a reliable basis to discuss the
      abundance of these clusters in the atmosphere. We predict concentrations up to
      9.24 * 10(15), 3.91 * 10(14), and 2.02 * 19(14) molecules.cm(-3) for water dimer,
      trimer, and tetramer in very hot and humid conditions and that the concentrations
      of these clusters would remain significant up to 10 km of altitude in the Earth's
      atmosphere. The concentration of O3...H2O is predicted to be between 1 and 2
      orders of magnitude higher than previous estimation from the literature: up to
      5.74 * 10(8) molecules.cm(-3) in very hot and humid conditions at ground level
      and up to 1.56 * 10(7) molecules.cm(-3) at 10 km of altitude of the Earth's
      atmosphere. The concentrations of the other ozone-water clusters, O3..(H2O)2,
      O3...(H2O)3, and O3...(H2O)4, are predicted to be very small or even negligible
      in the atmosphere. 

PMID- 24028452
TI  - Contributing to AJA.

PMID- 24028453
TI  - The soap maker.

PMID- 24028454
TI  - Systematic review of non-transportation rates and outcomes for older people who
      have fallen after ambulance service call-out.
AB  - AIM: To review the evidence regarding non-transported older people who have
      fallen in relation to non-transportation rates, outcomes and impact of alternate
      care pathways. METHOD: Electronic databases and reference lists of included
      studies (up to December 2011) were systematically searched. Studies were eligible
      if they included data on non-transportation rates, information on outcomes or
      alternate care pathways for older people who have fallen. RESULTS: Twelve studies
      were included. Non-transportation rates following a fall ranged from 11% to 56%.
      Up to 49% of non-transported people who have fallen had unplanned health-care
      contact within 28 days of the initial incident. Attendance by specially trained
      paramedics and individualised multifactorial interventions significantly reduced
      adverse events including subsequent falls, emergency ambulance calls, emergency
      department attendance and hospital admission. CONCLUSION: Limited but promising
      evidence shows that appropriate interventions can improve health outcomes of non
      transported older people who have fallen. Further studies are needed to explore
      alternate care pathways and promote more efficient use of health services.

PMID- 24028455
TI  - Ageing in an inconvenient paradise: the immigrant experiences of older Korean
      people in New Zealand.
AB  - AIM: The purpose of this paper is to explore the immigrant experiences of older
      Korean people and their intergenerational family relationships in the New Zealand
      context. METHODS: Data were collected from qualitative interviews with older
      people, community leaders and professionals in Christchurch and Auckland. Data
      analysis was conducted using concept mapping techniques in the cross-cultural
      context where two languages were simultaneously used. RESULTS: The findings of
      the study show that older Korean people in New Zealand were likely to face
      multiple challenges due to the combined effects of immigration and ageing in a
      new country. Some older people experienced difficulties in managing their
      immigrant lives and intergenerational relationships in the transnational family
      context in which their family members were dispersed across two or more nations.
      CONCLUSION: The immigrant experiences of older migrants might be affected by an
      'invisible' source of isolation and exclusion at familial, community, societal
      and transnational levels.

PMID- 24028456
TI  - What are older adults seeking? Factors encouraging or discouraging retirement
      village living.
AB  - AIMS: (1) To identify factors that older adults find encouraging or discouraging
      about the prospect of relocation to a retirement village; and (2) to identify
      features or facilities often associated with retirement communities that are most
      appealing to prospective residents. METHOD: Randomly selected community residents
      (n = 517), aged 55-94 years, from the Australian Capital Territory completed
      postal surveys to identify the characteristics associated with retirement
      villages that influence relocation decisions. RESULTS: The provision of outdoor
      living areas, support in maintaining independence, assisted living facilities and
      accessibility to medical facilities were identified as factors that would
      encourage relocation. Luxury services (e.g. heated swimming pools) were indicated
      as least likely to encourage relocation. Negative perceptions most influential in
      discouraging relocation reflected a fear of losing independence and privacy.
      CONCLUSIONS: Through identifying the expectations of prospective residents,
      retirement village providers may better tailor facilities to the needs of their
      target demographic.

PMID- 24028457
TI  - Epidemiology of ambulance responses to older people who have fallen in New South
      Wales, Australia.
AB  - AIM: To quantify the size and scope of the operational burden for a large
      ambulance service arising from older people who have fallen and to describe this
      population. METHODS: Retrospective analysis of ambulance records from New South
      Wales, Australia for emergency calls classified as 'falls' in the period 1 July
      2008 to 30 June 2009. RESULTS: There were 42 331 responses to people aged 65
      years or older, constituting 5.1% of total emergency workload. The median age of
      patients was 83 (interquartile range 76-87) and 62% were women. The transport
      rate was 76%. Transport to hospital was more likely during the day (odds ratio
      (OR) 1.8, 95% confidence interval (CI) 1.7-1.9) and on weekends (OR 1.06, 95%CI
      1.0-1.1). CONCLUSION: Falls by older people constitute approximately 5% of all
      emergency responses, of which one quarter are not transported to emergency
      department (ED) after paramedic assessment. Increasing the sophistication of
      ambulance dispatch processes to older people who have fallen, and continuing with
      the development of new models of care aimed at decreasing unnecessary transports
      to the EDs, should be a priority when planning ambulance service delivery for
      older people who have fallen.

PMID- 24028458
TI  - The prevalence of vitamin D deficiency and relationship with fracture risk in
      older women presenting in Australian general practice.
AB  - AIM: To investigate vitamin D status among older women and to explore
      relationships between vitamin D and fracture risk and vertebral fractures.
      METHODS: A total of 267 general practitioners recruited 2466 women aged >70 years
      with no known osteoporosis or fragility fracture. Serum 25-hydroxy vitamin D
      (25(OH)D), bone mineral density by dual-energy X-ray absorptiometry (DXA) and
      vertebral fracture on thoracolumbar X-ray were determined. RESULTS: A total of
      2368 women, median age 76 years, provided data and of these 13% were on vitamin D
      supplements. 25(OH)D levels were available for 907 (44.1%) of those not taking
      vitamin D. 88.3% of these had a level below 75 nmol/L. Serum 25(OH)D was
      negatively associated with age (P = 0.003) and body mass index (P < 0.001), and
      positively associated with lower latitude, femoral neck DXA T-score (P = 0.044)
      and being Caucasian (P < 0.001). CONCLUSIONS: The vitamin D status of community
      dwelling older Australian women is inadequate, yet the use of supplements is low.

PMID- 24028459
TI  - End-of-life care in a rehabilitation centre for older people in Australia.
AB  - AIM: To investigate processes at the end of life for patients who died in a
      subacute evaluation and management facility for older people. METHODS: A
      retrospective chart audit for patients (n = 55) who died in the previous 2 years
      was undertaken, recording a number of significant variables. RESULTS: Despite
      diagnosis of comorbid medical conditions, most participants were admitted for
      improved functioning or assessment for alternative accommodation. Consistent with
      this focus, the key contact person was most often an allied health team member.
      Not For Resuscitation order and/or power of attorney documents on admission were
      uncommon (<30%) as were referrals to palliative care specialist staff (13%),
      although an end-of-life discussion was recorded (90%) and often included as a new
      goal of care (71%). CONCLUSION: Factors likely to improve end-of-life care
      include advance care planning, earlier recognition of short prognosis and staff
      education.

PMID- 24028460
TI  - Impediments to applying the 'dignity of risk' principle in residential aged care
      services.
AB  - This discussion paper identifies four core factors currently impeding the
      application of the dignity of risk principle in residential aged care settings in
      Victoria, Australia: the fluctuating decision-making ability of residents;
      multiple participants in decision-making; discordance between espoused values and
      actions; and confusion and fear around legal responsibilities of care providers.
      Potential solutions identified include a conceptual shift in approach and
      consensus between key stakeholders, as well as more tangible solutions such as
      education and point-of-care decision support tools. 

PMID- 24028461
TI  - Transfer printing of thermoreversible ion gels for flexible electronics.
AB  - Thermally assisted transfer printing was employed to pattern thin films of high
      capacitance ion gels on polyimide, poly(ethylene terephthalate), and SiO2
      substrates. The ion gels consisted of 20 wt % block copolymer poly(styrene-b
      ethylene oxide-b-styrene and 80 wt % ionic liquid 1-ethyl-3-methylimidazolium
      bis(trifluoromethyl sulfonyl)amide. Patterning resolution was on the order of 10
      MUm. Importantly, ion gels containing the block polymer with short PS end blocks
      (3.4 kg/mol) could be transfer-printed because of thermoreversible gelation that
      enabled intimate gel-substrate contact at 100  degrees C, while gels with long PS
      blocks (11 kg/mol) were not printable at the same temperature due to poor wetting
      contact between the gel and substrates. By using printed ion gels as high
      capacitance gate insulators, electrolyte-gated thin-film transistors were
      fabricated that operated at low voltages (<1 V) with high on/off current ratios
      (~10(5)). Statistical analysis of carrier mobility, turn-on voltage, and on/off
      ratio for an array of printed transistors demonstrated the excellent
      reproducibility of the printing technique. The results show that transfer
      printing is an attractive route to pattern high-capacitance ion gels for flexible
      thin-film devices. 

PMID- 24028462
TI  - Novel Middle East respiratory syndrome and renal failure.

PMID- 24028464
TI  - Catalytic mechanism of the glycyl radical enzyme 4-hydroxyphenylacetate
      decarboxylase from continuum electrostatic and QC/MM calculations.
AB  - Using continuum electrostatics and QC/MM calculations, we investigate the
      catalytic cycle of the glycyl radical enzyme 4-hydroxyphenylacetate
      decarboxylase, an enzyme involved in the fermentative production of p-cresol from
      tyrosine in clostridia. On the basis of our calculations, we propose a five-step
      mechanism for the reaction. In the first step, the substrate 4
      hydroxyphenylacetate is activated by an unusual concerted abstraction of an
      electron and a proton. Namely, Cys503 radical abstracts an electron from the
      substrate and Glu637 abstracts a proton. Thus in total, a hydrogen atom is
      abstracted from the substrate. In the second step, the carboxylic group readily
      splits off from the phenoxy-acetate radical anion to give carbon dioxide. This
      decarboxylation step is coupled to a proton transfer from Glu637 back to the
      phenolic hydroxyl group which leads to a p-hydroxybenzyl radical. The remaining
      steps of the reaction involve a rotation of the Cys503 side chain followed by a
      proton transfer from Glu505 to Cys503 and a hydrogen atom transfer from Cys503 to
      the p-hydroxybenzyl radical to form p-cresol. The calculated mechanism agrees
      with experimental data suggesting that both Cys503 and Glu637 are essential for
      the catalytic function of 4-hydroxyphenylacetate decarboxylase and that the
      substrate requires a hydroxyl group in para-position to the acetate moiety. 

PMID- 24028463
TI  - Re-sequencing of the APOAI promoter region and the genetic association of the 
      75G > A polymorphism with increased cholesterol and low density lipoprotein
      levels among a sample of the Kuwaiti population.
AB  - BACKGROUND: APOAI, a member of the APOAI/CIII/IV/V gene cluster on chromosome
      11q23-24, encodes a major protein component of HDL that has been associated with
      serum lipid levels. The aim of this study was to determine the genetic
      association of polymorphisms in the APOAI promoter region with plasma lipid
      levels in a cohort of healthy Kuwaiti volunteers. METHODS: A 435 bp region of the
      APOAI promoter was analyzed by re-sequencing in 549 Kuwaiti samples. DNA was
      extracted from blood taken from 549 healthy Kuwaiti volunteers who had fasted for
      the previous 12 h. Univariate and multivariate analysis was used to determine
      allele association with serum lipid levels. RESULTS: The target sequence included
      a partial segment of the promoter region, 5'UTR and exon 1 located between
      nucleotides -141 to +294 upstream of the APOAI gene on chromosome 11. No novel
      single nucleotide polymorphisms (SNPs) were observed. The sequences obtained were
      deposited with the NCBI GenBank with accession number [GenBank: JX438706]. The
      allelic frequencies for the three SNPs were as follows: APOAI rs670G = 0.807;
      rs5069C = 0.964; rs1799837G = 0.997 and found to be in HWE. A significant
      association (p < 0.05) was observed for the APOAI rs670 polymorphism with
      increased serum LDL-C. Multivariate analysis showed that APOAI rs670 was an
      independent predictive factor when controlling for age, sex and BMI for both LDL
      C (OR: 1.66, p = 0.014) and TC (OR: 1.77, p = 0.006) levels. CONCLUSION: This
      study is the first to report sequence analysis of the APOAI promoter in an Arab
      population. The unexpected positive association found between the APOAI rs670
      polymorphism and increased levels of LDL-C and TC may be due to linkage
      disequilibrium with other polymorphisms in candidate and neighboring genes known
      to be associated with lipid metabolism and transport.

PMID- 24028465
TI  - Long-term improvements in oral communication skills and quality of peer relations
      in children with cochlear implants: parental testimony.
AB  - BACKGROUND: Few research studies have examined longitudinal improvements in oral
      communication skills and quality of peer relationships of children with implants.
      Moreover, although the emerging literature suggests that improvement in social
      functioning follows improvement in oral communication, it is still unknown what
      factors enhance or impede the relations between these constructs. METHODS: Based
      on parent interviews, the current study examined the long-term improvements in
      speech and oral language skills and relationships with hearing peers in 19
      implanted children. RESULTS: Results demonstrate that on average, children
      continue to improve in oral communication skills and quality of peer
      relationships even years after implantation, especially those with initial poorer
      skills. While oral communication ability and quality of peer relationships are
      strongly associated at each time point, gains in these two variables are
      associated only for some of the children. Other factors, including self
      confidence and peer acceptance, seem to moderate this relationship. Qualitative
      data are presented to illustrate these relations among variables and to assist in
      theory building. CONCLUSIONS: The results highlight the need for more specific
      examination of various developmental periods in combination with the progress of
      oral communication and peer relationships among children with implants.

PMID- 24028466
TI  - The benefits of a 5-day dysphagia intensive placement.
AB  - Finding practical dysphagia opportunities for students pre-qualification is
      challenging. Discussions with clinicians led to the development of a new
      placement model. The placement was just five days and had an accompanying
      workbook. The current study aimed to evaluate the benefits of the placement. Data
      were analysed from 40 students who attended an adult dysphagia placement and 13
      who attended a paediatric dysphagia placement. Measures included a pre and post
      self-rating questionnaire, qualitative feedback from clinical educators and
      students and a pre and post measure of knowledge using concept maps. Student self
      rating data indicated gains in experience, awareness, knowledge, clinical skills,
      competence, confidence and interest in dysphagia. Clinical educators and students
      also reported a range of benefits from this placement. Students who undertook a
      placement that focused on adult dysphagia significantly increased their knowledge
      of adult dysphagia, but this did not generalize to paediatric dysphagia. Despite
      reporting that they felt they had gained in knowledge of dysphagia, the students
      who did a paediatric dysphagia placement did not significantly increase their
      knowledge of dysphagia. The study raises a number of important considerations
      when designing placements including length, timing, intensity, how best to
      encourage generalization of knowledge, and how best to measure learning.

PMID- 24028467
TI  - Review of calls to an Australian teratogen information service regarding
      psychotropic medications over a 12-year period.
AB  - BACKGROUND: Telephone counselling services are increasingly utilised by consumers
      to obtain contemporary and confidential information about perinatal drug and
      toxin exposure. The use of such services in regard to psychotropic agents is
      unknown. AIM: To determine the frequency and types of calls to a New South Wales
      (NSW)-based telephone counselling service regarding perinatal psychotropic agent
      exposure between 2000 and 2011. METHODS: Retrospective analyses of MotherSafe
      call data between two epochs: I (2000-2005, n = 46,277) and II (2006-2011, n =
      118,587), total 164,864 calls. RESULTS: 25,698 (15.6%) calls were made about
      psychotropic agents: 16,218 (9.8%) about antidepressants, 3,145 calls (1.9%)
      about mood stabilisers/antiepileptic agents, 2,878 (1.7%) about benzodiazepines
      and 3,457 (2.1%) about antipsychotic drugs. Calls regarding psychotropic agents
      doubled in epoch II (18,231 vs 7,467, epoch I) but decreased as a proportion of
      total calls (I: 16.1% vs II: 15.4%, P < 0.001). Selective serotonin inhibitors
      (SSRIs) were the most common drugs of concern (>44% of total psychotropic calls).
      The proportion of calls regarding particular agents changed significantly between
      epochs, for example paroxetine (epoch I: 14.8% vs epoch II: 6.7% of all
      antidepressant calls, P < 0.001) and quetiapine (epoch 1: 10.6% vs epoch II:
      34.7% of all antipsychotic calls (P < 0.001). Calls from rural areas of NSW
      increased from 22.6 to 24.7% (P < 0.001). CONCLUSION: Consumer demand for
      information about the use of psychotropic agents for women of child-bearing age
      has increased considerably over the last decade, particularly in rural areas of
      Australia. This indicates a need to review current existing services,
      particularly for rural consumers.

PMID- 24028468
TI  - Vessel transformation in chronic wounds under topical negative pressure therapy:
      an immunohistochemical analysis.
AB  - The underlying physiological mechanism of topical negative pressure (TNP) therapy
      is not yet completely understood. This prospective clinical study aims to clarify
      a potential influence of TNP therapy on vessel proliferation and hypoxia in
      chronic wounds. TNP was applied on chronic wounds of 16 patients (-125 mmHg) to
      prepare them for a plastic-surgical reconstruction using free or pedicled flaps.
      Tissue biopsies were taken from the wound edge and wound bed at different time
      points. All samples were stained with haematoxylin and eosin, hypoxia-induced
      factor-1alpha and endothelial cell markers (CD31 and CD34) for the
      immunohistological analysis of inflammation, hypoxia and vessel proliferation.
      Between day 5 and day 8 of treatment, a considerable increase in blood vessel
      density could be observed, reaching a maximum of approximately 200% in contrast
      to the vessel density prior to treatment. In addition, the number of hypoxic and
      inflammatory cells was found to be increased at particular time points. This
      study demonstrates a stimulating effect on vessel proliferation under TNP
      treatment. TNP appears to support (neo-) angiogenesis and transformation of
      chronic non-healing wounds in a physiological wound healing process when combined
      with surgical debridement. This effect underlines the positive influence of TNP
      in the treatment of chronic wounds as shown by various clinical reports. 

PMID- 24028469
TI  - Seasonal phenology of interactions involving short-lived annual plants, a
      multivoltine herbivore and its endoparasitoid wasp.
AB  - Spatial-temporal realism is often missing in many studies of multitrophic
      interactions, which are conducted at a single time frame and/or involving
      interactions between insects with a single species of plant. In this scenario, an
      underlying assumption is that the host-plant species is ubiquitous throughout the
      season and that the insects always interact with it. We studied interactions
      involving three naturally occurring wild species of cruciferous plants, Brassica
      rapa, Sinapis arvensis and Brassica nigra, that exhibit different seasonal
      phenologies, and a multivoltine herbivore, the large cabbage white butterfly,
      Pieris brassicae, and its gregarious endoparasitoid wasp, Cotesia glomerata. The
      three plants have very short life cycles. In central Europe, B. rapa grows in
      early spring, S. arvensis in late spring and early summer, and B. nigra in mid to
      late summer. P. brassicae generally has three generations per year, and C.
      glomerata at least two. This means that different generations of the insects must
      find and exploit different plant species that may differ in quality and which may
      be found some distance from one another. Insects were either reared on each of
      the three plant species for three successive generations or shifted between
      generations from B. rapa to S. arvensis to B. nigra. Development time from
      neonate to pupation and pupal fresh mass were determined in P. brassicae and egg
      to-adult development time and body mass in C. glomerata. Overall, herbivores
      performed marginally better on S. arvensis and B. nigra plants than on B. rapa
      plants. Parasitoids performance was closely tailored with that of the host.
      Irrespective as to whether the insects were shifted to a new plant in successive
      generations or not, development time of P. brassicae and C. glomerata decreased
      dramatically over time. Our results show that there were some differences in
      insect development on different plant species and when transferred from one
      species to another. However, all three plants were of generally high quality in
      terms of insect performance. We discuss ecological and evolutionary constraints
      on insects that must search in new habitats for different plant species over
      successive generations.

PMID- 24028470
TI  - A multivariate view of the evolution of sexual dimorphism.
AB  - Sexual differences are often dramatic and widespread across taxa. Their
      extravagance and ubiquity can be puzzling because the common underlying genome of
      males and females is expected to impede rather than foster phenotypic divergence.
      Widespread dimorphism, despite a shared genome, may be more readily explained by
      considering the multivariate, rather than univariate, framework governing the
      evolution of sexual dimorphism. In the univariate formulation, differences in
      genetic variances and a low intersexual genetic correlation (rMF) can facilitate
      the evolution of sexual dimorphism. However, studies that have analysed sex
      specific differences in heritabilities or genetic variances do not always find
      significant differences. Furthermore, many of the reported estimates of rMF are
      very high and positive. When monomorphic heritabilities and a high rMF are
      present together, the evolution of sexual dimorphism on a trait-by-trait basis is
      severely constrained. By contrast, the multivariate formulation has greater
      generality and more flexibility. Although the number of multivariate sexual
      dimorphism studies is low, almost all support sex-specific differences in the G
      (variance-covariance) matrix; G matrices can differ with respect to size and/or
      orientation, affecting the response to selection differently between the sexes.
      Second, whereas positive values of the univariate quantity rMF only hinder
      positive changes in sexual dimorphism, positive covariances in the intersexual
      covariance B matrix can either help or hinder. Similarly, the handful of studies
      reporting B matrices indicate that it is often asymmetric, so that B can affect
      the evolution of single traits differently between the sexes. Multivariate
      approaches typically demonstrate that genetic covariances among traits can
      strongly constrain trait evolution when compared with univariate approaches. By
      contrast, in the evolution of sexual dimorphism, a multivariate view potentially
      reveals more opportunities for sexual dimorphism to evolve by considering the
      effect sex-specific selection has on sex-specific G matrices and an asymmetric B
      matrix. 

PMID- 24028471
TI  - Multiple infections, kin selection and the evolutionary epidemiology of parasite
      traits.
AB  - The coinfection of a host by several parasite strains is known to affect
      selective pressures on parasite strategies of host exploitation. I present a
      general model of coinfections that ties together kin selection models of
      virulence evolution and epidemiological models of multiple infections. I derive
      an analytical expression for the invasion fitness of a rare mutant in a
      population with an arbitrary distribution of the multiplicity of infection (MOI)
      across hosts. When a single mutation affects parasite strategies in all MOI
      classes, I show that the evolutionarily stable level of virulence depends on a
      demographic average of within-host relatedness across all host classes. This
      generalization of previous kin selection results requires that within-host
      parasite densities do not vary between hosts. When host exploitation strategies
      are allowed to vary across classes, I show that the strategy of host exploitation
      in a focal MOI class depends on the relative magnitudes of parasite reproductive
      values in the focal class and in the next. Thus, in contrast to previous
      findings, lower within-host relatedness in competitive parasite interactions can
      potentially correspond to either higher or lower levels of virulence. 

PMID- 24028472
TI  - Nectar sugar composition of European Caryophylloideae (Caryophyllaceae) in
      relation to flower length, pollination biology and phylogeny.
AB  - Floral nectar composition has been explained as an adaptation to factors that are
      either directly or indirectly related to pollinator attraction. However, it is
      often unclear whether the sugar composition is a direct adaptation to pollinator
      preferences. Firstly, the lower osmolality of sucrose solutions means that they
      evaporate more rapidly than hexose solutions, which might be one reason why
      sucrose-rich nectar is typically found in flowers with long tubes (adapted to
      long-tongued pollinators), where it is better protected from evaporation than in
      open or short-tubed flowers. Secondly, it can be assumed that temperature
      dependent evaporation is generally lower during the night than during the day so
      that selection pressure to secrete nectar with high osmolality (i.e. hexose-rich
      solutions) is relaxed for night-active flowers pollinated at night. Thirdly, the
      breeding system may affect selection pressure on nectar traits; that is, for
      pollinator-independent, self-pollinated plants, a lower selective pressure on
      nectar traits can be assumed, leading to a higher variability of nectar sugar
      composition independent of pollinator preferences, nectar accessibility and
      nectar protection. To analyse the relations between flower tube length, day vs.
      night pollination and self-pollination, the nectar sugar composition was
      investigated in 78 European Caryophylloideae (Caryophyllaceae) with different
      pollination modes (diurnal, nocturnal, self-pollination) using high-performance
      liquid chromatography (HPLC). All Caryophylleae species (Dianthus and relatives)
      were found to have nectar with more than 50% sucrose, whereas the sugar
      composition of Sileneae species (Silene and relatives) ranged from 0% to 98.2%.
      In the genus Silene, a clear dichotomous distribution of sucrose- and hexose
      dominant nectars is evident. We found a positive correlation between the flower
      tube length and sucrose content in Caryophylloideae, particularly in day
      flowering species, using both conventional analyses and phylogenetically
      independent contrasts. 

PMID- 24028473
TI  - Analysis of comorbidities and therapeutic approach for allergic rhinitis in a
      pediatric population in Spain.
AB  - BACKGROUND: Allergic rhinitis (AR) is the most common chronic disease in
      children. The main objective of this study was to analyze the comorbidities and
      therapeutic approaches for AR in a Spanish pediatric population. METHODS:
      Children aged 6 to 12 years with AR were included in an observational, cross
      sectional, multicenter study. RESULTS: 1,275 children were recruited from 271
      centers. AR was intermittent in 59.5% of cases, persistent in 40.5%, seasonal in
      60.7%, and perennial in 39.3% of patients. The most frequent comorbidities were
      conjunctivitis (53.6%), asthma (49.5%), atopic dermatitis (40%),
      rhinosinusitis(26.1%), otitis media (23.8%), and adenoid hypertrophy (17.3%).
      Overall, patients with persistent, moderate or severe, AR were more likely to
      present comobidities, except for food allergy and urticaria. The most common
      drugs used for treatment of AR were oral antihistamines(76%), nasal
      corticosteroids(49%) and a combination of both (45%). Antihistamines and nasal
      corticosteroids were used on demand (<18 days) in 38 and 41% of patients,
      respectively; for 18-30 days in 22 and 27%; for 1-3 months in 31 and 29%; and for
      more than 3 months in 8 and 3%, respectively. Eye drops were used in 32% and
      specific immunotherapy in 21% of patients. CONCLUSION: Comorbidities are frequent
      in children with AR, supporting the notion of allergy as a systemic disease.
      Severity and duration of AR were significantly associated with presence of most
      of comorbidities. The most common drugs used for AR treatment were oral
      antihistamines, followed by nasal corticosteroids and a combination of both used
      on demand.

PMID- 24028474
TI  - Cardioprotective effects of adenosine within the border and remote areas of
      myocardial infarction.
AB  - BACKGROUND: Adenosine may have beneficial effects on left ventricular function
      after myocardial infarction (MI), but the magnitude of this effect on remote and
      MI areas is controversial. We assessed the long-term effects of adenosine after
      MI using electrocardiogram-triggered 18 F-fluorodeoxyglucose positron emission
      tomography. METHODS: Wistar rats were subjected to coronary ligation and
      randomized into three groups treated daily for 2 months by NaCl (control; n = 7),
      2-chloroadenosine (CADO; n = 8) or CADO with 8-sulfophenyltheophilline, an
      antagonist of adenosine receptors (8-SPT; n = 8). RESULTS: After 2 months,
      control rats exhibited left ventricular remodelling, with increased end-diastolic
      volume and decreased ejection fraction. Left ventricular remodelling was not
      significantly inhibited by CADO. Segmental contractility, as assessed by the
      change in myocardial thickening after 2 months, was improved in CADO rats
      compared to control rats (+1.6% +/- 0.8% vs. -2.3% +/- 0.8%, p < 0.001). This
      improvement was significant in border (+5.6% +/- 0.8% vs. +1.5% +/- 0.8%, p <
      0.001) and remote (-4.0% +/- 1.0% vs. -10.4% +/- 1.3%, p < 0.001) segments, but
      absent in MI segments. Histological analyses revealed that CADO reduced fibrosis,
      cardiomyocyte hypertrophy and apoptosis. Protective effects of CADO were blunted
      by 8-SPT. CONCLUSION: Long-term administration of adenosine protects the left
      ventricle from contractile dysfunction following MI.

PMID- 24028475
TI  - Aorto-right atrial fistula at aortotomy site following surgical myectomy.

PMID- 24028476
TI  - Affect as a mediator between self-efficacy and quality of life among Chinese
      cancer survivors in China.
AB  - Previous studies have shown that self-efficacy influences cancer survivors'
      quality of life. As most of the relevant findings are based on Caucasian cancer
      survivors, whether the same relationship holds among Asian cancer patients and
      through what mechanism self-efficacy influences quality of life are unclear. This
      study examined the association between self-efficacy and quality of life among
      Chinese cancer survivors, and proposed affect (positive and negative) as a
      mediator between self-efficacy and quality of life. A sample of 238 Chinese
      cancer survivors (75% female, mean age = 55.7) were recruited from Beijing,
      China. Self-efficacy, affect (positive and negative) and quality of life were
      measured in a questionnaire package. Self-efficacy was positively associated with
      quality of life and positive affect, and negatively associated with negative
      affect. Path analyses revealed the direct effect from self-efficacy to quality of
      life and the indirect effects from self-efficacy to quality of life through
      positive affect and negative affect. The beneficial role of self-efficacy in
      Chinese cancer survivors' quality of life and the mediating role of affect in
      explaining the relationship between self-efficacy and quality of life are
      supported. Future interventions should include self-care and affect regulation
      skills training to enhance cancer survivors' self-efficacy and positive affect,
      as this could help to improve Chinese cancer survivors' quality of life. 

PMID- 24028477
TI  - Contrast-enhanced ultrasonography is a valid technique for the assessment of
      renal microvascular perfusion dysfunction in diabetic Goto-Kakizaki rats.
AB  - AIM: To evaluate the reliability of contrast-enhanced ultrasonography (CEUS) for
      the detection of renal microvascular blood perfusion in a type 2 diabetic Goto
      Kakizaki (GK) rat model. METHODS: Male GK and Wistar rats at the age of 4, 12 and
      20 weeks (n=10, respectively) were used for the study. Real-time and haemodynamic
      imaging of the renal cortex was performed using CEUS with SonoVue. Outage time
      intensity curves (TICs) were applied for the analysis of basic intensity, slope
      rates of the ascending (S1) and descending curves (S2), time to peak (TTP), half
      time of peak descending (HDT), peak intensity (PI), and total area under the
      curve (AUC). Immunohistochemical staining for endothelial cells (ECs) was
      performed using the CD34 monoclonal antibody for the quantification of
      microvessel density and distribution. RESULTS: Images of the renal cortex
      microvascular beds after injection of SonoVue in the rats were rapidly and
      clearly displayed, and it is easy to differentiate the enhanced and faded images
      of renal perfusion. The TICs of the GK rats were much wider than the controls;
      however, no significant changes in PI were found in all aged rats.
      Ultrasonographic quantitative analysis revealed a decrease in S1 and S2, and an
      increase in TTP, HDT and AUC in the 12- and 20-week-old GK rats compared with the
      controls (P<0.05). Moreover, the 20-week-old GK rats had much lower glomerular
      density and smaller distribution area of CD34-positive ECs, which was in parallel
      with more severe proteinuria, GBM thickening, glomerulosclerosis and interstitial
      vascular damages (P<0.05). Interestingly, negative correlations between AUC and
      glomerular microvessel density or distribution were detected, respectively
      (P<0.05). CONCLUSIONS: Contrast-enhanced ultrasonography is a valid technique for
      the real-time and dynamic assessment of renal cortex microvascular perfusion and
      haemodynamic characterization in GK rats.

PMID- 24028478
TI  - Accountability in research: policies and quality assurance. Guest editorial.

PMID- 24028479
TI  - Research misconduct and its federal regulation: the origin and history of the
      Office of Research Integrity--with personal views by ORI's former associate
      director for investigative oversight.
AB  - Misconduct in science and research became the subject of significant public
      attention and Congressional scrutiny beginning in the 1970s and 1980s, which led
      to public statements, policies, and finally formal federal regulations being
      promulgated by Government agency officials. The Office of Research Integrity
      (ORI) in the Department of Health and Human Services was a major and very visible
      component of this process. This article provides a detailed history of the first
      two decades of federal research misconduct regulations and of ORI's history
      (under extremely difficult and unfair challenges), including personal views by
      the former ORI chief investigator and associate director. 

PMID- 24028481
TI  - Retrospective reflections of a whistleblower: opinions on misconduct responses.
AB  - Almost 10 years ago, when I was in my fourth year of graduate school, my fellow
      graduate students discovered that our thesis advisor had engaged in misconduct by
      falsifying and fabricating data in two grant applications. We informed the
      university and my advisor resigned. This event was a turning point in my life.
      Years later, I have gathered my thoughts and reflections on the experience. I
      believe we must first prevent what misconduct we can. But unfortunately some
      misconduct will still occur and in those circumstances we must respond to protect
      those affected by the misconduct and to progress beyond the event. In so doing,
      we get the most value out of scientific research. 

PMID- 24028480
TI  - Understanding research misconduct: a comparative analysis of 120 cases of
      professional wrongdoing.
AB  - We analyzed 40 cases of falsification, fabrication, or plagiarism (FFP),
      comparing them to other types of wrongdoing in research (n=40) and medicine
      (n=40). Fifty-one variables were coded from an average of 29 news or
      investigative reports per case. Financial incentives, oversight failures, and
      seniority correlate significantly with more serious instances of FFP. However,
      most environmental variables were nearly absent from cases of FFP and none were
      more strongly present in cases of FFP than in other types of wrongdoing.
      Qualitative data suggest FFP involves thinking errors, poor coping with research
      pressures, and inadequate oversight. We offer recommendations for education,
      institutional investigations, policy, and further research.

PMID- 24028482
TI  - The emergence of the Responsible Conduct of Research (RCR) in PHS policy and
      practice.
AB  - The Responsible Conduct of Research (RCR) is now an established academic field
      taught at virtually every major American research university and generates a
      growing volume of research and pedagogical literature. Paradoxically, it is a
      field without a consensually agreed upon definition, goals, foundational
      theories, research agenda, and pedagogical methodology. It has been suggested
      that RCR as currently being taught is ineffective in preventing misconduct and
      improving the quality of research. The following short history of RCR, focused
      mainly on Federal policy and practice, explains how this curious state of affairs
      developed and persists and concludes with some suggestions for the future of RCR
      instruction. 

PMID- 24028483
TI  - Data audit as a way to prevent/contain misconduct.
AB  - Research misconduct is frequently in the media headlines. There is consensus
      among leading experts on research integrity that the prevalence of misconduct in
      research is at least 1%, and shoddy work may even go over 5%. Unfortunately,
      misconduct in research impacts all walks of life from drugs to human subject
      protections, innovations, economy, policy, and even our national security. The
      main method of detecting research misconduct depends primarily on whistleblowers.
      The current regulations are insufficient since dependence on whistleblowers
      manifests itself as an accidental hit or miss. No other endeavor in our society
      depends on such a poor system of discovery of misconduct to remedy it. Nearly a
      quarter of a century ago, I proposed data audit as a means to prevent/contain
      research misconduct. The audit has to protect the creative process and be non
      obtrusive. Data audit evaluates the degree of correspondence of published data
      with the source data. The proposed data audit does not require any changes in the
      way researchers carry out their work. 

PMID- 24028485
TI  - Promoting responsible conduct of research: a Canadian perspective.
AB  - This article compares the current Canadian and American approaches to governing
      the responsible conduct of research. The Canadian Secretariat on Responsible
      Conduct of Research acts on behalf of Canada's three federal research agencies to
      implement their Framework on Responsible Conduct of Research. It operates not on
      the basis of regulatory authority, like its U.S. counterpart, the Office of
      Research Integrity, but rather on the basis of making compliance a condition of
      eligibility for funding. Both offices are dedicated to promoting good research
      practices and to enforcing good standards of research practice. 

PMID- 24028484
TI  - A brief history of RCR education.
AB  - Responsible conduct of research (RCR) education is now common throughout the
      United States, primarily in response to federal requirements beginning with the
      National Institutes of Health in 1989. Despite this long history, RCR education
      programs remain highly disparate, often with ill-defined content, format, and
      goals, and minimal evidence for effectiveness. However because it is widely
      believed that such programs can have value, it is hoped that a review of what is
      available, and how that came to pass, will highlight what has been done well and
      where gaps still remain. 

PMID- 24028487
TI  - Assessing effort: differentiating performance and symptom validity.
AB  - The current study aimed to clarify the relationship among the constructs involved
      in neuropsychological assessment, including cognitive performance, symptom self
      report, performance validity, and symptom validity. Participants consisted of 120
      consecutively evaluated individuals from a veteran's hospital with mixed referral
      sources. Measures included the Wechsler Adult Intelligence Scale-Fourth Edition
      Full Scale IQ (WAIS-IV FSIQ), California Verbal Learning Test-Second Edition
      (CVLT-II), Trail Making Test Part B (TMT-B), Test of Memory Malingering (TOMM),
      Medical Symptom Validity Test (MSVT), WAIS-IV Reliable Digit Span (RDS), Post
      traumatic Check List-Military Version (PCL-M), MMPI-2 F scale, MMPI-2 Symptom
      Validity Scale (FBS), MMPI-2 Response Bias Scale (RBS), and the Postconcussive
      Symptom Questionnaire (PCSQ). Six different models were tested using confirmatory
      factor analysis (CFA) to determine the factor model describing the relationships
      between cognitive performance, symptom self-report, performance validity, and
      symptom validity. The strongest and most parsimonious model was a three-factor
      model in which cognitive performance, performance validity, and self-reported
      symptoms (including both standard and symptom validity measures) were separate
      factors. The findings suggest failure in one validity domain does not necessarily
      invalidate the other domain. Thus, performance validity and symptom validity
      should be evaluated separately. 

PMID- 24028488
TI  - Aspirin-induced apoptosis of yeast cells is associated with mitochondrial
      superoxide radical accumulation and NAD(P)H oxidation.
AB  - In previous studies, we observed that aspirin, a promising cancer-preventive
      agent, induces apoptosis in mitochondrial manganese superoxide dismutase (MnSOD)
      deficient Saccharomyces cerevisiae cells grown aerobically in ethanol medium. In
      this study, we show that aspirin-induced apoptosis is associated with a
      significant increase in mitochondrial and cytosolic O2 .- and oxidation of
      mitochondrial NAD(P)H. A concomitant rise in the level of cytosolic CuZnSOD
      activity failed to compensate for mitochondrial MnSOD deficiency. However, an
      observed increase in activity of Escherichia coli FeSOD targeted to the
      mitochondrial matrix of the MnSOD-deficient yeast cells, markedly decreased
      aspirin-induced accumulation of mitochondrial O2 .-, significantly increased the
      mitochondrial NAD(P)H level and rescued the apoptotic phenotype. Indeed,
      recombinant yeast cells expressing E. coli FeSOD behaved in a similar manner to
      the parent wild-type yeast cells with native mitochondrial MnSOD activity. Wild
      type cells consistently showed a decrease in mitochondrial O2 .- and an increase
      in mitochondrial NAD(P)H levels in the presence of aspirin in ethanol medium. In
      fact, in wild-type cells, our studies supported an antioxidant action of aspirin.
      Taken together, our results indicate that a pro-oxidant effect of aspirin
      occurring predominantly in cells with compromised mitochondrial redox balance may
      be enough to overcome antioxidant defences resulting in apoptosis, as observed in
      MnSOD-deficient yeast cells.

PMID- 24028489
TI  - Zebra: a web server for bioinformatic analysis of diverse protein families.
AB  - During evolution of proteins from a common ancestor, one functional property can
      be preserved while others can vary leading to functional diversity. A systematic
      study of the corresponding adaptive mutations provides a key to one of the most
      challenging problems of modern structural biology - understanding the impact of
      amino acid substitutions on protein function. The subfamily-specific positions
      (SSPs) are conserved within functional subfamilies but are different between them
      and, therefore, seem to be responsible for functional diversity in protein
      superfamilies. Consequently, a corresponding method to perform the bioinformatic
      analysis of sequence and structural data has to be implemented in the common
      laboratory practice to study the structure-function relationship in proteins and
      develop novel protein engineering strategies. This paper describes Zebra web
      server - a powerful remote platform that implements a novel bioinformatic
      analysis algorithm to study diverse protein families. It is the first application
      that provides specificity determinants at different levels of functional
      classification, therefore addressing complex functional diversity of large
      superfamilies. Statistical analysis is implemented to automatically select a set
      of highly significant SSPs to be used as hotspots for directed evolution or
      rational design experiments and analyzed studying the structure-function
      relationship. Zebra results are provided in two ways - (1) as a single all-in-one
      parsable text file and (2) as PyMol sessions with structural representation of
      SSPs. Zebra web server is available at http://biokinet.belozersky.msu.ru/zebra . 

PMID- 24028491
TI  - Differences in children and adolescents' ability of reporting two CVS-related
      visual problems.
AB  - The present study examined whether children and adolescents can correctly report
      dry eyes and blurred distance vision, two visual problems associated with
      computer vision syndrome. Participants are 913 children and adolescents aged 6
      17. They were asked to report their visual problems, including dry eyes and
      blurred distance vision, and received an eye examination, including tear film
      break-up time (TFBUT) and visual acuity (VA). Inconsistency was found between
      participants' reports of dry eyes and TFBUT results among all 913 participants as
      well as for all of four subgroups. In contrast, consistency was found between
      participants' reports of blurred distance vision and VA results among 873
      participants who had never worn glasses as well as for the four subgroups. It was
      concluded that children and adolescents are unable to report dry eyes correctly;
      however, they are able to report blurred distance vision correctly. Three
      practical implications of the findings were discussed. PRACTITIONER SUMMARY:
      Little is known about children's ability to report their visual problems, an
      issue critical to diagnosis and treatment of children's computer vision syndrome.
      This study compared children's self-reports and clinic examination results and
      found children can correctly report blurred distance vision but not dry eyes.

PMID- 24028490
TI  - O-phenyl carbamate and phenyl urea thiiranes as selective matrix
      metalloproteinase-2 inhibitors that cross the blood-brain barrier.
AB  - Brain metastasis occurs in 20-40% of cancer patients. Treatment is mostly
      palliative, and the inability of most drugs to penetrate the brain presents one
      of the greatest challenges in the development of therapeutics for brain
      metastasis. Matrix metalloproteinase-2 (MMP-2) plays important roles in invasion
      and vascularization of the central nervous system and represents a potential
      target for treatment of brain metastasis. Carbonate, O-phenyl carbamate, urea,
      and N-phenyl carbamate derivatives of SB-3CT, a selective and potent gelatinase
      inhibitor, were synthesized and evaluated. The O-phenyl carbamate and urea
      variants were selective and potent inhibitors of MMP-2. Carbamate 5b was
      metabolized to the potent gelatinase inhibitor 2, which was present at
      therapeutic concentrations in the brain. In contrast, phenyl urea 6b crossed the
      blood-brain barrier, however, higher doses would result in therapeutic brain
      concentrations. Carbamate 5b and urea 6b show potential for intervention of MMP-2
      dependent diseases such as brain metastasis. 

PMID- 24028492
TI  - A-site-ordered perovskite MnCu3V4O12 with a 12-coordinated manganese(II).
AB  - A novel cubic perovskite MnCu3V4O12 has been synthesized at a high pressure and
      high temperature of 12 GPa and 1373 K. This compound crystallizes in the A-site
      ordered perovskite structure (space group Im3) with lattice constant a =
      7.26684(10) A at room temperature. The most notable feature of this compound lies
      in the fact that the Mn(2+) ion is surrounded by 12 equidistant oxide ions to
      form a regular icosahedron; the situation of Mn(2+) is unprecedented for the
      crystal chemistry of an oxide. An anomalously large atomic displacement parameter
      U(iso)= 0.0222(8) A(2) is found for Mn(2+) at room temperature, indicating that
      the thermal oscillation of the small Mn(2+) ion in a large icosahedron is fairly
      active. Magnetic susceptibility and electric resistivity measurements reveal that
      3d electrons of Mn(2+) ions are mainly localized, while 3d electrons in Cu(2+)
      and V(4+) ions are delocalized and contribute to the metallic conduction.

PMID- 24028493
TI  - Comparison of viremia of type II porcine reproductive and respiratory syndrome
      virus in naturally infected pigs by zip nucleic acid probe-based real-time PCR.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is a RNA
      virus with high genetic variation. This virus causes significant economic losses
      in most pig-producing countries. The clinical presentation of PRRSV ranges from
      asymptomatic to devastating. In this study, we developed a sensitive and specific
      zip nucleic acid probe-based real-time PCR assay to evaluate the viremia of
      natural PRRSV-infected pigs in Taiwan. Serum samples were collected from 577 pigs
      aged 5-12 weeks. These include 444 clinically healthy pigs and 133 symptomatic
      pigs were confirmed to have porcine respiratory disease complex (PRDC). RESULTS:
      Viremia was quantified in 79 of the 444 (17.8%) clinically healthy pigs and in
      112 of the 133 (84.2%) PRDC cases. Viremias were significantly more common in
      pigs with PRDC compared with the clinically healthy pigs (P <0.0001). These
      results suggest that a high viral load is a major feature of PRRSV-affected pigs.
      CONCLUSIONS: ZNA probe-based real-time PCR can be a useful tool to diagnose
      symptomatic and asymptomatic PRRSV-infected pigs. The presence of this marker in
      a sample of animals with high PRRSV loads (>10(4.2) PRRSV genomes/MUl of serum)
      seems to indicate that it correlates with the presence of PRDC in pigs.

PMID- 24028495
TI  - Well-tempered metadynamics as a tool for characterizing multi-component,
      crystalline molecular machines.
AB  - The well-tempered, smoothly converging form of the metadynamics algorithm has
      been implemented in classical molecular dynamics simulations and used to obtain
      an estimate of the free energy surface explored by the molecular rotations in the
      plastic crystal, octafluoronaphthalene. The biased simulations explore the full
      energy surface extremely efficiently, more than 4 orders of magnitude faster than
      unbiased molecular dynamics runs. The metadynamics collective variables used have
      also been expanded to include the simultaneous orientations of three neighboring
      octafluoronaphthalene molecules. Analysis of the resultant three-dimensional free
      energy surface, which is sampled to a very high degree despite its significant
      complexity, demonstrates that there are strong correlations between the molecular
      orientations. Although this correlated motion is of limited applicability in
      terms of exploiting dynamical motion in octafluoronaphthalene, the approach used
      is extremely well suited to the investigation of the function of crystalline
      molecular machines. 

PMID- 24028494
TI  - Myosin VI contributes to maintaining epithelial barrier function.
AB  - BACKGROUND: Epithelial barrier dysfunction is associated with the pathogenesis of
      a number of immune inflammations; the etiology is not fully understood. The
      fusion of endosome/lysosome is a critical process in the degradation of endocytic
      antigens in epithelial cells. Recent reports indicate that myosin VI (myo6) is
      involved in the activities of endosomes. The present study aims to investigate
      the role of myo6 in epithelial barrier dysfunction. RESULTS: The endosome
      accumulation was observed in myo6-deficient Rmcs. More than 80% endosomes were
      fused with lysosomes in naive Rmcs while less than 30% endosomes were fused with
      lysosomes in the myo6-deficient Rmcs. The myo6-deficient Rmc monolayers showed
      high permeability to a macromolecular antigen, ovalbumin, the latter still
      conserved the antigenicity, which induced strong T cell activation. CONCLUSIONS:
      We conclude that myo6 plays a critical role in the fusion of endosome/lysosome in
      Rmc epithelial cells. Deficiency of myo6 compromises the epithelial barrier
      function.

PMID- 24028496
TI  - Glycoconjugated amphiphilic polymers via click-chemistry for the encapsulation of
      quantum dots.
AB  - Herein, we present a strategy for the glycoconjugation of nanoparticles (NPs),
      with a special focus on fluorescent quantum dots (QDs), recently described by us
      as "preassembly" approach. Therein, prior to the encapsulation of diverse
      nanoparticles by an amphiphilic poly(isoprene)-b-poly(ethylene glycol) diblock
      copolymer (PI-b-PEG), the terminal PEG appendage was modified by covalently
      attaching a carbohydrate moiety using Huisgen-type click-chemistry. Successful
      functionalization was proven by NMR spectroscopy. The terminally glycoconjugated
      polymers were subsequently used for the encapsulation of QDs in a phase transfer
      process, which fully preserved fluorescence properties. Binding of these
      nanoconstructs to the lectin Concanavalin A (Con A) was studied via surface
      plasmon resonance (SPR). Depending on the carbohydrate moiety, namely, D-manno
      heptulose, D-glucose, D-galactose, 2-deoxy-2-{[methylamino)carbonyl]amino}-D
      glucopyranose ("des(nitroso)-streptozotocin"), or D-maltose, the glycoconjugated
      QDs showed enhanced affinity constants due to multivalent binding effects. None
      of the constructs showed toxicity from 0.001 to 1 MUM (particle concentration)
      using standard WST and LDH assays on A549 cells.

PMID- 24028497
TI  - Effects of drying eggs and egg storage on hatchability and development of
      Anopheles arabiensis.
AB  - BACKGROUND: The mass rearing of insects requires a large colony from which
      individuals can be harvested for sterilization and release. Attention is given to
      larval food requirements and to handling and rearing conditions to ensure
      predictability and synchrony of development. Maximizing production requires
      optimized adult holding to ensure mating success, blood feeding and oviposition.
      Appropriate egg storage and harvesting is necessary to compensate any unpredicted
      reduction in egg production. METHODS: Anopheles arabiensis eggs were collected on
      wet filter paper in eggs cups. The eggs were cleaned and then dried over a
      suction device with adjustable speed and time. The effects of drying, storage
      time and storage condition (wet, dry and bulk with relative humidity 75 +/- 5%
      and storage temperatures of 10, 15 and 20 degrees C) on hatch rate, duration of
      larval stages (L1 to pupal stage), duration of L1 to adult emergence, survival of
      L1 to pupal stage and the survival of L1 to adult emergence were investigated.
      Post drying and post storage hatch rates were determined by counting hatched and
      unhatched eggs and were confirmed by counting the viable larvae in the rearing
      medium. RESULTS: The hatch rate of eggs dried at wind speeds of 1.0 or 1.8 m/s
      was not significantly different from the control, but eggs dried at 3.0 m/s
      resulted in very low (64%) hatchability as compared to the control (82%). Eggs
      stored at 20 degrees C and 75 +/- 5% RH in bulk in an aerated vial showed better
      survival than eggs stored in wet or dry conditions at 10 or 15 degrees C. No
      significant changes in larval duration and survival were recorded after six days
      of bulk storage. CONCLUSION: Anopheles arabiensis eggs can be stored in bulk at
      20 degrees C and 75 +/- 5% RH for six days without any decrease in hatch rate,
      and up to 9 days with no impact on larval development.

PMID- 24028498
TI  - syn-/anti-Anthradithiophene derivative isomer effects on semiconducting
      properties.
AB  - Isomerically pure syn-/anti-anthradithiophene derivatives have been developed in
      the past few years. Although anti-isomers showed higher field-effect mobilities
      than mixture of isomers have been reported, a detailed comparison of syn-isomer
      and anti-isomer molecules has not been carried out. In this study, we took newly
      synthesized pure unsubstituted syn-/anti-anthradithiophenes (ADTs) and compared
      their single crystal structures, physical properties and semiconducting behavior
      with a previously studied syn-/anti-dimethylanthradithiophenes (DMADTs). Although
      the both isomers were typical herringbone packing structures with similar
      parameters, anti-isomers involved less disordered atoms in the crystal packing.
      The results from thermal analysis, UV-vis spectra, photo luminescence spectra and
      cyclic voltammograms of syn-/anti-anthradithiophenes were nearly the in the solid
      state as well as in solution. However, field-effect transistors showed obvious
      differences with mobilities of 0.12 cm(2) V(-1) s(-1) for anti-anthradithiophene
      and 0.02 cm(2) V(-1) s(-1) for syn-anthradithiophene. Because the crystallinity
      of thin-films measured by X-ray diffraction (XRD) and atomic force microscopy
      (AFM) seems to be better in syn-isomers, the differences in transistor
      performance are likely attributed to local defects affecting intermolecular
      interactions, such as disorder in the crystal packing and charge-dipole
      interactions. 

PMID- 24028499
TI  - Resonance enhancement via imidazole substitution predicts new cation receptors.
AB  - Design and development of cation receptors represent a fascinating area of
      research, particularly in dealing with chemical and biological applications that
      require fine-tuning of cation-pi interactions. The electronic nature of a
      substituent is largely responsible for tuning the strength of cation-pi
      interaction, and recent studies have shown that substituent resonance effect
      contributes significantly to such interactions. Using substituent resonance
      effect as a key electronic factor, we have proposed new cation-pi receptors
      (1...M(+)-4...M(+); M(+) = Li(+), Na(+), K(+), NH4(+), and NMe4(+)). B3LYP/6
      311+G(d,p) density functional theory (DFT) calculations show that by using a
      strategy of resonance donation from six nitrogen atoms via three substituted
      imidazole subunits, more than 4-fold increase in cation-pi interaction energy
      (E(M)(+)) can be achieved for a single phenyl ring compared to benzene. The
      E(M)(+) (M(+) = NH4(+), NMe4(+)) of 4...M(+), wherein M(+) interacts with only
      one phenyl ring, is significantly higher than E(M)(+) of a known cation host with
      several aromatic rings (abstract figure). Our hypothesis on resonance enhancement
      of cation-pi interaction is verified using several pi-systems (5-10) containing a
      lone pair bearing six nitrogens and observed that a nitrogen lone pair attached
      to a double bond is more effective for donation than the lone pair that is
      directly attached to the benzenoid ring. Further, a convenient strategy to design
      electron rich pi-systems is provided on the basis of topographical analysis of
      molecular electrostatic potential.

PMID- 24028500
TI  - The spatial patterns of directional phenotypic selection.
AB  - Local adaptation, adaptive population divergence and speciation are often
      expected to result from populations evolving in response to spatial variation in
      selection. Yet, we lack a comprehensive understanding of the major features that
      characterise the spatial patterns of selection, namely the extent of variation
      among populations in the strength and direction of selection. Here, we analyse a
      data set of spatially replicated studies of directional phenotypic selection from
      natural populations. The data set includes 60 studies, consisting of 3937
      estimates of selection across an average of five populations. We performed meta
      analyses to explore features characterising spatial variation in directional
      selection. We found that selection tends to vary mainly in strength and less in
      direction among populations. Although differences in the direction of selection
      occur among populations they do so where selection is often weakest, which may
      limit the potential for ongoing adaptive population divergence. Overall, we also
      found that spatial variation in selection appears comparable to temporal (annual)
      variation in selection within populations; however, several deficiencies in
      available data currently complicate this comparison. We discuss future research
      needs to further advance our understanding of spatial variation in selection. 

PMID- 24028502
TI  - Prevalence of hypertension in an Iranian population.
AB  - BACKGROUND: The prevalence of HTN varies considerably worldwide. This study was
      carried out to illustrate the prevalence of hypertension in a group of Iranian
      population based on the data gathered for Iranian Multi-centric Osteoporosis
      Studies (IMOS). METHODS: This study analyzes the systolic and diastolic blood
      pressure from the IMOS, a multi-centric cross-sectional study carried out on
      apparently healthy men and women in urban areas of major Iranian cities to study
      bone health. RESULTS: Overall, 26.21% of the studied cases were estimated to be
      hypertensive; the condition was more prevalent among older males. Each year
      increase in age was associated with 1.070 higher risk of developing hypertension.
      CONCLUSION: Hypertension is quite prevalent among Iranian population and the
      prevalence of the condition is rising in the context of progressive rise in age
      and BMI.

PMID- 24028501
TI  - Endoplasmic reticulum aminopeptidase-1 alleles associated with increased risk of
      ankylosing spondylitis reduce HLA-B27 mediated presentation of multiple antigens.
AB  - Ankylosing spondylitis (AS) is a chronic systemic arthritic disease that leads to
      significant disability and loss of quality of life in the ~0.5% of the worldwide
      human population it affects. There is currently no cure for AS and mechanisms
      underlying its pathogenesis remain unclear. AS is highly genetic, with over 70%
      of the genetic risk being associated with the presence of HLA-B27 and endoplasmic
      reticulum aminopeptidase-1 (ERAP1) alleles. Furthermore, gene-gene interactions
      between HLA-B27 and ERAP1 AS risk alleles have recently been confirmed. Here, we
      demonstrate that various ERAP1 alleles can differentially mediate surface
      expression of antigens presented by HLA-B27 on human cells. Specifically, for all
      peptides tested, we found that an ERAP1 variant containing high AS risk SNPs
      reduced the amount of the peptide presented by HLA-B27, relative to low AS risk
      ERAP1 variants. These results were further validated using peptide catalysis
      assays in vitro, suggesting that high AS risk alleles have an enhanced catalytic
      activity that more rapidly destroys many HLA-B27-destined peptides, a result that
      correlated with decreased HLA-B27 presentation of the same peptides. These
      findings suggest that one mechanism underlying AS pathogenesis may involve an
      altered ability for AS patients harboring both HLA-B27 and high AS risk ERAP1
      alleles to correctly display a variety of peptides to the adaptive arm of the
      immune system, potentially exposing such individuals to higher AS risk due to
      abnormal display of pathogen or self-derived peptides by the adaptive immune
      system.

PMID- 24028503
TI  - A closer examination of atraumatic dressings for optimal healing.
AB  - The concept that undisturbed wound healing, optimised by dressing choice,
      improves wound outcomes has become a focal point of consideration when evaluating
      wound management regimens in recent years. However, little evidence exists
      related to wound contact layers and the potential detrimental effects of the
      intimate contact with the wound bed. The aim of this study was to evaluate the
      effects of atraumatic wound contact dressings on the healing of partial-thickness
      wounds in comparison to untreated air-exposed wounds. Using an in vivo porcine
      wound model the handling properties of each dressing in terms of adhesion were
      analysed. Methods of wound characterisation included histological analysis of
      granulation tissue formation and epithelialisation and this was correlated with
      various clinical observations. Differences were found between dressings in terms
      of adherence to the wound bed and surrounding skin, capacity to retain wound
      exudates and enhancement of healing. 

PMID- 24028504
TI  - Clinical patterns of lichen planopilaris in patients with vulval lichen planus.

PMID- 24028505
TI  - Understanding the parents of children with special needs: collaboration between
      health, social and education networks.
AB  - CONTEXT: In 2003, Quebec's Ministry of Health and Social Services (MSSS) and the
      Ministry of Education, Recreation and Sports (MELS) concluded the Agreement for
      the complementarity of services between the health and social services network
      and the education network. The objectives of the current investigation were to
      evaluate the implementation of this Agreement and its impact upon renewal of
      practices and services, and to investigate the consequences for children with
      special needs and their families. The specific focus of this article is to
      describe parents' perspectives regarding the impact of this Agreement upon them
      and their children. METHODS: Interviews were conducted with 56 parents of
      children with disabilities, social maladjustment or learning difficulties across
      the province of Quebec. Data were analysed using content analysis. RESULTS: Most
      parents were not directly aware of any contact between school staff and health or
      social professionals, although discussions might have been held without their
      knowledge. The intervention plans seemed to be the main vehicle through which
      some parents perceived collaboration to be occurring. For parents, the impact
      upon actual practices or collaborative work is either minimal or non-existent.
      CONCLUSION: School inclusion of children with special needs is a challenge for
      all societies. The Agreement illustrates the Quebec government's intent to
      promote an alliance between two complex networks and has the potential to greatly
      benefit children and their families. However, more concrete action is required in
      order to realize specific changes regarding work cohesion and service
      organization for these groups.

PMID- 24028506
TI  - Splice site SNPs of phospholipase PLCXD3 are significantly associated with
      variant and sporadic Creutzfeldt-Jakob disease.
AB  - BACKGROUND: Variant Creutzfeldt-Jakob disease is an infectious,
      neurodegenerative, protein-misfolding disease, of the prion disease family,
      originally acquired through ingestion of meat products contaminated with bovine
      spongiform encephalopathy (BSE). Public health concern was increased by the
      discovery of human-to-human transmission via blood transfusion. This study has
      verified a novel genetic marker linked to disease risk. METHODS: SNP imputation
      and association testing indicated those genes that had significant linkage to
      disease risk and one gene was investigated further with Sanger resequencing.
      Results from variant Creutzfeldt-Jakob disease were compared with those from
      sporadic (idiopathic) Creutzfeldt-Jakob disease and published controls. RESULTS:
      The most significant disease risk, in addition to the prion protein gene, was for
      the phosphatidylinositol-specific phospholipase C, X domain containing 3 (PLCXD3)
      gene. Sanger resequencing of CJD patients across a region of PLCXD3 with known
      variants confirmed three SNPs associated with variant and sporadic CJD.
      CONCLUSIONS: These data provide the first highly significant confirmation of SNP
      allele frequencies for a novel CJD candidate gene providing new avenues for
      investigating these neurodegenerative prion diseases. The phospholipase PLCXD3 is
      primarily expressed in the brain and is associated with lipid catabolism and
      signal transduction.

PMID- 24028508
TI  - Parental illness, attachment dimensions, and health beliefs: testing the
      cognitive-behavioural and interpersonal models of health anxiety.
AB  - The cognitive-behavioral and interpersonal models of health anxiety propose that
      parental illness could be a contributory factor to the development of health
      anxiety but through different mechanisms. The cognitive-behavioral model suggests
      that exposure to parental illness may lead to health beliefs that could increase
      health anxiety. In contrast, the interpersonal model proposes that parental
      illness may contribute to the development of an insecure attachment pattern and
      consequently health anxiety. To assess the additive value of the models, 116
      emerging adults (i.e. aged 18-25) who had a parent diagnosed with a serious
      medical illness (e.g. cancer, multiple sclerosis) completed measures of health
      anxiety, adult attachment dimensions, and health beliefs. Attachment anxiety,
      attachment avoidance, health beliefs, and death of the ill parent were
      statistically significant predictors of health anxiety. The results provide
      support for both models of health anxiety. Theoretical implications and
      directions for future research are discussed. 

PMID- 24028507
TI  - Effect of low-level laser therapy on the expression of inflammatory mediators and
      on neutrophils and macrophages in acute joint inflammation.
AB  - INTRODUCTION: Inflammation of the synovial membrane plays an important role in
      the pathophysiology of osteoarthritis (OA). The synovial tissue of patients with
      initial OA is characterized by infiltration of mononuclear cells and production
      of proinflammatory cytokines and other mediators of joint injury. The objective
      was to evaluate the effect of low-level laser therapy (LLLT) operating at 50 mW
      and 100 mW on joint inflammation in rats induced by papain, through
      histopathological analysis, differential counts of inflammatory cells
      (macrophages and neutrophils), as well as gene expression of interleukin 1-beta
      and 6 (IL-1beta and IL-6), and protein expression of tumor necrosis factor alpha
      (TNFalpha). METHODS: Male Wistar rats (n = 60) were randomly divided into four
      groups of 15 animals, namely: a negative control group; an inflammation injury
      positive control group; a 50 mW LLLT group, subjected to injury and treated with
      50 mW LLLT; and a 100 mW LLLT group, subjected to injury and treated with 100 mW
      LLLT. The animals were subject to joint inflammation (papain solution, 4%) and
      then treated with LLLT (808 nm, 4 J, 142.4 J/cm(2), spot size 0.028 for both
      groups). On the day of euthanasia, articular lavage was collected and immediately
      centrifuged; the supernatant was saved for analysis of expression of TNFalpha
      protein by enzyme-linked immunosorbent assay and expression of IL-1beta and IL-6
      mRNA by real-time polymerase chain reaction. A histologic examination of joint
      tissue was also performed. For the statistical analysis, analysis of variance
      with Tukey's post-hoc test was used for comparisons between each group. All data
      are expressed as mean values and standard deviation, with P < 0.05. RESULTS:
      Laser treatment with 50 mW was more efficient than 100 mW in reducing cellular
      inflammation, and decreased the expression of IL-1beta and IL-6. However, the 100
      mW treatment led to a higher reduction of TNFalpha compared with the 50 mW
      treatment. CONCLUSIONS: LLLT with 50 mW was more efficient in modulating
      inflammatory mediators (IL-1beta, IL-6) and inflammatory cells (macrophages and
      neutrophils), which correlated with the histology that showed a reduction in the
      inflammatory process.

PMID- 24028509
TI  - Four principles for achieving good indoor air quality.

PMID- 24028510
TI  - Limitations of climate chamber studies into thermal comfort and workers'
      performance.

PMID- 24028511
TI  - Metabolic ecology.
AB  - Ecological theory that is grounded in metabolic currencies and constraints offers
      the potential to link ecological outcomes to biophysical processes across
      multiple scales of organization. The metabolic theory of ecology (MTE) has
      emphasized the potential for metabolism to serve as a unified theory of ecology,
      while focusing primarily on the size and temperature dependence of whole-organism
      metabolic rates. Generalizing metabolic ecology requires extending beyond
      prediction and application of standardized metabolic rates to theory focused on
      how energy moves through ecological systems. A bibliometric and network analysis
      of recent metabolic ecology literature reveals a research network characterized
      by major clusters focused on MTE, foraging theory, bioenergetics, trophic status,
      and generalized patterns and predictions. This generalized research network,
      which we refer to as metabolic ecology, can be considered to include the scaling,
      temperature and stoichiometric models forming the core of MTE, as well as
      bioenergetic equations, foraging theory, life-history allocation models, consumer
      resource equations, food web theory and energy-based macroecology models that are
      frequently employed in ecological literature. We conclude with six points we
      believe to be important to the advancement and integration of metabolic ecology,
      including nomination of a second fundamental equation, complementary to the first
      fundamental equation offered by the MTE.

PMID- 24028513
TI  - Children and guns: A call to disarm.

PMID- 24028512
TI  - A robust genetic system for producing heterodimeric native and mutant cytochrome
      bc(1).
AB  - The ubihydroquinone:cytochrome c oxidoreductase, or cytochrome bc1, is central to
      the production of ATP by oxidative phosphorylation and photophosphorylation in
      many organisms. Its three-dimensional structure depicts it as a homodimer with
      each monomer composed of the Fe-S protein, cytochrome b, and cytochrome c1
      subunits. Recent genetic approaches successfully produced heterodimeric variants
      of this enzyme, providing insights into its mechanism of function. However, these
      experimental setups are inherently prone to genetic rearrangements as they carry
      repeated copies of cytochrome bc1 structural genes. Duplications present on a
      single replicon (one-plasmid system) or a double replicon (two-plasmid system)
      could yield heterogeneous populations via homologous recombination or other
      genetic events at different frequencies, especially under selective growth
      conditions. In this work, we assessed the origins and frequencies of genetic
      variations encountered in these systems and describe an improved variant of the
      two-plasmid system. We found that use of a recombination-deficient background
      (recA) minimizes spontaneous formation of co-integrant plasmids and renders the
      homologous recombination within the cytochrome b gene copies inconsequential. On
      the basis of the data, we conclude that both the newly improved RecA-deficient
      and the previously used RecA-proficient two-plasmid systems reliably produce
      native and mutant heterodimeric cytochrome bc1 variants. The two-plasmid system
      developed here might contribute to the study of "mitochondrial heteroplasmy"-like
      heterogeneous states in model bacteria (e.g., Rhodobacter species) suitable for
      bioenergetics studies. In the following paper (DOI 10.1021/bi400561e), we
      describe the use of the two-plasmid system to produce and characterize, in
      membranes and in purified states, an active heterodimeric cytochrome bc1 variant
      with unusual intermonomer electron transfer properties.

PMID- 24028514
TI  - Bilateral natal clefts in a neonate.

PMID- 24028519
TI  - Left Amyand's hernia in children: method, management and myth.

PMID- 24028520
TI  - Breast is best.

PMID- 24028521
TI  - Chest pain: virtual or pathological?

PMID- 24028523
TI  - Haemoglobin SC disease presenting as hip pain and urinary retention.

PMID- 24028524
TI  - Toy magnet ingestion and small bowel obstruction: a lesson for both
      paediatricians and surgeons.

PMID- 24028525
TI  - Double orifice mitral valve in rheumatic heart disease.
AB  - A 55-year-old female, presented to our outpatient department with complaints of
      dyspnea on exertion, NYHA grade II for 7 years, which had progressed to NYHA
      Grade III in the past 6 months. An echocardiogram done showed severe mitral
      stenosis with mitral valve fused in the middle to create an appearance of 2
      separate valves (complete bridge type) with 2 separate turbulent jets of flow
      across these valves. No other congenital anomaly was seen. Due to presence of
      severe subvalvular disease, she was sent for elective mitral valve replacement.
      This case demonstrates that a careful analysis of the subvalvular apparatus of
      the mitral valve is needed before making a decision for definitive treatment of
      this condition.

PMID- 24028526
TI  - Cyclic RGD-linked polymeric micelles for targeted delivery of platinum anticancer
      drugs to glioblastoma through the blood-brain tumor barrier.
AB  - Ligand-mediated drug delivery systems have enormous potential for improving the
      efficacy of cancer treatment. In particular, Arg-Gly-Asp peptides are promising
      ligand molecules for targeting alphavbeta3/alphavbeta5 integrins, which are
      overexpressed in angiogenic sites and tumors, such as intractable human
      glioblastoma (U87MG). We here achieved highly efficient drug delivery to U87MG
      tumors by using a platinum anticancer drug-incorporating polymeric micelle (PM)
      with cyclic Arg-Gly-Asp (cRGD) ligand molecules. Intravital confocal laser
      scanning microscopy revealed that the cRGD-linked polymeric micelles (cRGD/m)
      accumulated rapidly and had high permeability from vessels into the tumor
      parenchyma compared with the PM having nontargeted ligand, "cyclic-Arg-Ala-Asp"
      (cRAD). As both cRGD/m- and cRAD-linked polymeric micelles have similar
      characteristics, including their size, surface charge, and the amount of
      incorporated drugs, it is likely that the selective and accelerated accumulation
      of cRGD/m into tumors occurred via an active internalization pathway, possibly
      transcytosis, thereby producing significant antitumor effects in an orthotopic
      mouse model of U87MG human glioblastoma. 

PMID- 24028527
TI  - A study of the structural properties and thermal stability of human Bcl-2 by
      molecular dynamics simulations.
AB  - The anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein interacts with several
      proteins that regulate the apoptotic properties of cells. In this research, we
      conduct several all-atom molecular dynamics (MD) simulations under high
      temperature unfolding conditions, from 400 to 800 K, for 25 ns. These simulations
      were performed using a model of an engineered Bcl-2 human protein (Bcl-2
      Delta22Sigma3), which lacks 22 C-terminal residues of the transmembrane domain.
      The aim of this study is to gain insight into the structural behavior of Bcl-2
      Delta22Sigma3 by mapping the conformational movements involved in Bcl-2 stability
      and its biological function. To build a Bcl-2-Delta22Sigma3 three-dimensional
      model, the protein core was built by homology modeling and the flexible loop
      domain (FLD, residues 33-91) by ab initio methods. Further, the entire protein
      model was refined by MD simulations. Afterwards, the production MD simulations
      showed that the FLD at 400 and 500 K has several conformations reaching into the
      protein core, whereas at 600 K some of the alpha-helices were lost. At 800 K, the
      Bcl-2 core is destabilized suggesting a possible mechanism for protein unfolding,
      where the alpha helices 1 and 6 were the most stable, and a reduction in the
      number of hydrogen bonds initially occurs. In conclusion, the structural changes
      and the internal protein interactions suggest that the core and the FLD are
      crucial components of Bcl-2 in its function of regulate ng access to the
      recognition sites of kinases and caspases. 

PMID- 24028528
TI  - Patients using antifungals following laryngectomy: a qualitative study of
      community pharmacists in the North of England.
AB  - OBJECTIVE: To explore community pharmacists' understanding and opinions in
      relation to the prevention of fungal colonisation of voice prostheses amongst
      laryngectomy patients. METHOD: Semi-structured interviews were conducted on a
      purposive sample of 12 community pharmacists from the North of England.
      Interviews were undertaken until data saturation was reached and responses were
      transcribed verbatim and analysed using a thematic approach. KEY FINDINGS: Six
      themes emerged from the data analysis. These were: terminology confusion about
      laryngectomy, stoma and voice prostheses; smoking as a risk factor for the
      development of laryngeal cancer; using nystatin to prevent biofilm formation;
      counselling information related to nystatin; prescription intervention and
      additional education in relation to laryngectomy. The theme of counselling
      information related to nystatin use and additional education was a key finding:
      our data show that when dispensing nystatin to patients with a voice prosthesis,
      community pharmacists would either give no advice related to medication use or
      would give incorrect advice that may lead to premature prosthesis failure amongst
      this patient group. CONCLUSION: This study highlights that community pharmacists
      lack understanding in relation to laryngectomy and are unaware of the off-label
      doses and administration methods of the drugs (specifically nystatin) used to
      prevent fungal colonisation on voice prostheses. Additional information sources
      in the form of an educational leaflet, possibly obtained through the local
      department of speech and language therapy, would be perceived as a valuable
      resource to support community pharmacists who are required to manage these
      patients in the community.

PMID- 24028529
TI  - Automation: how much is too much?
AB  - The headlong rush to automate continues apace. The dominant question still
      remains whether we can automate, not whether we should automate. However, it is
      this latter question that is featured and considered explicitly here. The
      suggestion offered is that unlimited automation of all technical functions will
      eventually prove anathema to the fundamental quality of human life. Examples of
      tasks, pursuits and past-times that should potentially be excused from the
      automation imperative are discussed. This deliberation leads us back to the
      question of balance in the cooperation, coordination and potential conflict
      between humans and the machines they create. 

PMID- 24028530
TI  - Incidence of symbiotic dsRNA 'killer' viruses in wild and domesticated yeast.
AB  - Viruses are found in almost all organisms and physical habitats. One interesting
      example is the yeast viral 'killer system'. The virus provides the host with a
      toxin directed against strains that do not carry it, while the yeast cell enables
      its propagation. Although yeast viruses are believed to be common, they have been
      actually described only for a limited number of yeast isolates. We surveyed 136
      Saccharomyces cerevisiae and S. paradoxus strains of known origin and
      phylogenetic relatedness. Of these, 14 (c. 10%) were infected by killer viruses
      of one of the three types: K1, K2 or K28. As many as 34 strains (c. 25%) were not
      sensitive to at least one type of the killer toxin. In most cases, resistance did
      not disappear after attempts to cure the host strains from their viruses,
      suggesting that it was encoded in the host's genome. In terms of phylogeny,
      killer strains appear to be more related to each other than to nonkiller ones. No
      such tendency is observed for the phenotype of toxin resistance. Our results
      suggest that even if the killer toxins are not always present, they do play
      significant role in yeast ecology and evolution.

PMID- 24028531
TI  - Four-dimensional dose evaluation of inhomogeneous dose distributions planned for
      non-small cell lung cancer patients with lymph node involvement.

PMID- 24028532
TI  - Simultaneous stereotactic body radiation therapy of a primary non-small cell lung
      cancer and synchronous carcinoma in situ in a medically inoperable patient: case
      report.
AB  - The co-incidence of synchronous intraepithelial neoplasia and early stage
      invasive lung cancer is not a rare phenomenon. The need for curative treatment
      and the invasive potential of squamous cell pulmonary carcinoma in situ have been
      a topic of controversy. Surgical resection still remains the treatment of choice.
      Varieties of endoscopic techniques such as brachytherapy were developed as an
      alternative to surgery in selected patients. External beam radiation therapy has
      been used traditionally in combination with endobronchial brachytherapy in the
      treatment of roentgenographically occult lung cancer, and can be offered for all
      patients, but is handicapped, because these tumors are radiographically
      invisible. We report the first case of a pulmonary carcinoma in situ that was
      successfully treated with stereotactic body radiation therapy. 

PMID- 24028533
TI  - Learning a Markov Logic network for supervised gene regulatory network inference.
AB  - BACKGROUND: Gene regulatory network inference remains a challenging problem in
      systems biology despite the numerous approaches that have been proposed. When
      substantial knowledge on a gene regulatory network is already available,
      supervised network inference is appropriate. Such a method builds a binary
      classifier able to assign a class (Regulation/No regulation) to an ordered pair
      of genes. Once learnt, the pairwise classifier can be used to predict new
      regulations. In this work, we explore the framework of Markov Logic Networks
      (MLN) that combine features of probabilistic graphical models with the
      expressivity of first-order logic rules. RESULTS: We propose to learn a Markov
      Logic network, e.g. a set of weighted rules that conclude on the predicate
      "regulates", starting from a known gene regulatory network involved in the switch
      proliferation/differentiation of keratinocyte cells, a set of experimental
      transcriptomic data and various descriptions of genes all encoded into first
      order logic. As training data are unbalanced, we use asymmetric bagging to learn
      a set of MLNs. The prediction of a new regulation can then be obtained by
      averaging predictions of individual MLNs. As a side contribution, we propose
      three in silico tests to assess the performance of any pairwise classifier in
      various network inference tasks on real datasets. A first test consists of
      measuring the average performance on balanced edge prediction problem; a second
      one deals with the ability of the classifier, once enhanced by asymmetric
      bagging, to update a given network. Finally our main result concerns a third test
      that measures the ability of the method to predict regulations with a new set of
      genes. As expected, MLN, when provided with only numerical discretized gene
      expression data, does not perform as well as a pairwise SVM in terms of AUPR.
      However, when a more complete description of gene properties is provided by
      heterogeneous sources, MLN achieves the same performance as a black-box model
      such as a pairwise SVM while providing relevant insights on the predictions.
      CONCLUSIONS: The numerical studies show that MLN achieves very good predictive
      performance while opening the door to some interpretability of the decisions.
      Besides the ability to suggest new regulations, such an approach allows to cross
      validate experimental data with existing knowledge.

PMID- 24028534
TI  - Health-related quality of life of patients awaiting kidney and simultaneous
      pancreas-kidney transplants.
AB  - AIM: Patients undergoing kidney and simultaneous pancreas-kidney (SPK)
      transplants are younger and fitter than the general dialysis population.
      Intuitively these patients might have better quality of life (QOL) than the
      general dialysis population, but their QOL scores are not well characterized. The
      aim of this study was to compare QOL of patients about to undergo kidney or SPK
      transplants with Australian dialysis outcomes and practice patterns (DOPPS) data
      and multiple comorbidity and age-adjusted general population data. METHODS:
      Patients attending Westmead Hospital for transplants from August 2009 to December
      2011 were invited to complete the Kidney Disease QOL-SF(TM) 1.3 (KDQOL-SF(TM)
      1.3) questionnaire regarding their immediate pretransplant QOL. This QOL
      instrument is predictive of hospitalizations and mortality. The questionnaire was
      completed within 4 weeks of transplantation. RESULTS: Of 180 patients seen within
      4 weeks of transplantation 95 (53%) responded, with no differences from non
      responders in age, sex, comorbidities or perioperative complications. Compared
      with DOPPS, these patients had better physical function and less pain, but
      significantly lower scores for role physical (CI: -19 to -4, P=0.004) and role
      emotional (CI: -17 to -2, P=0.018). Patients undergoing SPK transplants reported
      even poorer general health, energy, social support and function. Patients had
      lower emotional and social function than people with multiple comorbidities, with
      whom they shared poor general and mental health and vitality. Scores were
      markedly lower than the general population except for bodily pain (female).
      CONCLUSION: Younger, fitter patients are more vulnerable to effects of their
      illness on social, emotional and physical interactions and may benefit from
      targeted support.

PMID- 24028536
TI  - State of hydrophobic and hydrophilic ionic liquids in aqueous solutions: are the
      ions fully dissociated?
AB  - Molecular dynamics simulations were performed for aqueous solutions of five ionic
      liquids (ILs): 1-ethyl-3-methylimidazolium ([C2mim])
      bis(trifluoromethanesulfonyl) imide ([NTf2]), 1-n-butyl-3-methylimidazolium
      ([C4mim]) [NTf2], 1-n-hexyl-3-methylimidazolium ([C6mim]) [NTf2], [C2mim]
      ethylsulfate ([C2H5SO4]), and [C2mim] chloride (Cl) to determine whether the ions
      of these ILs are associated at relatively high dilutions and whether the
      association is governed by hydrophobicity/hydrophilicity of the ILs. The adaptive
      biasing force technique was applied to calculate the potential of mean force
      (PMF) for each IL ion pair. For all of the ILs, the PMF is characterized by two
      distinct contact minima in which the ions have different relative conformations.
      The hydrophobic ILs bearing the anion [NTf2](-) exist predominantly in the
      associative state; the strength of the association of these ILs increases with
      increase in the alkyl chain length. The most hydrophilic IL [C2mim] Cl was
      determined to be almost fully dissociated at the concentration examined in the
      study. [C2mim] [C2H5SO4] showed hydration behavior that was intermediate between
      that exhibited by the ILs in which the anion is substituted with either Cl(-) or
      [NTf2](-) paired with [C2mim](+). Association constants for these ILs were also
      computed. Radial distribution functions calculated by constraining the ions at
      the contact minima showed that hydration of the anion plays the dominant role in
      determining the microscopic behavior of these ILs in aqueous solutions. 

PMID- 24028535
TI  - Structure-kinetic relationships--an overlooked parameter in hit-to-lead
      optimization: a case of cyclopentylamines as chemokine receptor 2 antagonists.
AB  - Preclinical models of inflammatory diseases (e.g., neuropathic pain, rheumatoid
      arthritis, and multiple sclerosis) have pointed to a critical role of the
      chemokine receptor 2 (CCR2) and chemokine ligand 2 (CCL2). However, one of the
      biggest problems of high-affinity inhibitors of CCR2 is their lack of efficacy in
      clinical trials. We report a new approach for the design of high-affinity and
      long-residence-time CCR2 antagonists. We developed a new competition association
      assay for CCR2, which allows us to investigate the relation of the structure of
      the ligand and its receptor residence time [i.e., structure-kinetic relationship
      (SKR)] next to a traditional structure-affinity relationship (SAR). By applying
      combined knowledge of SAR and SKR, we were able to re-evaluate the hit-to-lead
      process of cyclopentylamines as CCR2 antagonists. Affinity-based optimization
      yielded compound 1 with good binding (Ki = 6.8 nM) but very short residence time
      (2.4 min). However, when the optimization was also based on residence time, the
      hit-to-lead process yielded compound 22a, a new high-affinity CCR2 antagonist
      (3.6 nM), with a residence time of 135 min. 

PMID- 24028537
TI  - Reactions of Fe+ and FeO+ with C2H2, C2H4, and C2H6: temperature-dependent
      kinetics.
AB  - We present the first temperature-dependent rate constants and branching ratios
      for the reactions of Fe(+) and FeO(+) with C2H2, C2H4, and C2H6 from 170 to 700
      K. Fe(+) is observed to react only by association with the three hydrocarbons,
      with temperature dependencies of T(-2) to T(-3). FeO(+) reacts with C2H2 and C2H4
      at the collision rate over the temperature range, and their respective product
      branchings show similar temperature dependences. In contrast, the reaction with
      ethane is collisional at 170 K but varies as T(-0.5), while the product branching
      remains essentially flat with temperature. These variations in reactivity are
      discussed in terms of the published reactive potential surfaces. The
      effectiveness of Fe(+) as an oxygen-transfer catalyst toward the three
      hydrocarbons is also discussed. 

PMID- 24028538
TI  - Atrazine affects the circadian rhythm of Microcystis aeruginosa.
AB  - This study provides original data regarding the effects of atrazine (Atr) on the
      circadian rhythm of the cyanobacterium Microcystis aeruginosa. The results reveal
      that the circadian rhythms of the central circadian oscillator genes reached
      their peaks from 1 to 2.5 h after the light was switched on, and the circadian
      rhythms of physiologically related genes were highly synchronized with the
      central circadian oscillator genes. These circadian rhythms were consistent with
      cell growth at the physiological level. The circadian rhythms of the central
      circadian oscillator genes were altered, and their peaks disappeared or were
      delayed by the Atr treatment. Therefore, the rhythms of the physiologically
      related genes in this study also changed to synchronize the new circadian
      rhythms. And the physiological parameters were tightly correlated with the gene
      circadian rhythm in the Atr treatment, suggesting that Atr affects M. aeruginosa
      growth by possibly altering the circadian expression patterns of the clock.
      Furthermore, this influence is related to the exposure time point of Atr. Thus,
      chemicals treated in the suitable exposure time point can exert their fullest
      effects against cell growth. 

PMID- 24028539
TI  - Carbon and hydrogen stable isotope fractionation associated with the anaerobic
      degradation of propane and butane by marine sulfate-reducing bacteria.
AB  - The anaerobic degradation of propane and butane is typically initiated by
      activation via addition to fumarate. Here we investigated the mechanism of
      activation under sulfate-reducing conditions by one pure culture (strain BuS5)
      and three enrichment cultures employing stable isotope analysis. Stable isotope
      fractionation was compared for cultures incubated with or without substrate
      diffusion limitation. Bulk enrichment factors were significantly higher in mixed
      vs. static incubations. Two dimensional factors, given by the correlation of
      stable isotope fractionation of both carbon and hydrogen at their reactive
      positions (Lambda reactive position, Lambdarp), were compared to analyse the
      activation mechanisms. A characteristic reactive position isotope fractionation
      pattern was observed, distinct from aerobic degradation. Lambdarp values ranged
      from 10.5 to 11.8 for propane and from 7.8 to 9.4 for butane. Incubations of
      strain BuS5 with deuterium-labelled n-alkanes indicated that butane was activated
      solely at the subterminal C atom. In contrast, propane was activated mainly at
      the subterminal C atom but also significantly at the terminal C atoms. A
      conservative estimate suggests that about 70% of the propane activation events
      occurred at the subterminal C atom and about 30% at the terminal C atoms.

PMID- 24028540
TI  - Role of nicotinic acid and nicotinamide in nicorandil-induced ulcerations: from
      hypothesis to demonstration.
AB  - Nicorandil, a nicotinamide ester, was first reported to be involved in the
      induction of oral ulcers in 1997. Since then, many reports of single or multiple
      nicorandil-induced ulcerations (NIUs) have been reported. We hypothesised that in
      the case of high-dosage nicorandil or after an increased dosage of nicorandil,
      nicotinic acid and nicotinamide (two main metabolites of nicorandil) cannot
      appropriately merge into the endogenous pool of nicotinamide adenine
      dinucleotide/phosphate, which leads to abnormal distribution of these metabolites
      in the body. In recent or maintained trauma, nicotinamide increases blood flow at
      the edge of the raw area, inducing epithelial proliferation, while nicotinic acid
      ulcerates this epithelial formation, ultimately flooding the entire scar. We
      demonstrate, by comparison to a control patient non-exposed to nicorandil, an
      abnormal amount of nicotinic acid (*38) and nicotinamide (*11) in the ulcerated
      area in a patient with NIUs. All practitioners, especially geriatricians,
      dermatologists and surgeons, must be aware of these serious and insidious side
      effects of nicorandil. It is critical to rapidly reassess the risk-benefit ratio
      of this drug for any patient, and not only for those with diverticular diseases. 

PMID- 24028541
TI  - Cystatin C, creatinine, estimated glomerular filtration, and long-term mortality
      in stroke patients.
AB  - Renal dysfunction is associated with mortality in patients after ischemic stroke.
      Cystatin C is a potentially superior marker of renal function compared to
      creatinine and estimated glomerular filtration rate (GFR). In our observational
      cohort study, 390 Caucasian patients suffered from acute ischemic stroke (mean
      age 70.9 years; 183 women and 207 men) were included and prospectively followed
      up to maximal 56 months. Serum creatinine and cystatin C were measured at
      admission to the hospital; GFR was estimated according to CKD-EPI creatinine and
      CKD-EPI creatinine/cystatin equations. According to values of serum creatinine,
      estimated GFR and serum cystatin C patients were divided into quintiles. In the
      follow-up period, 191 (49%) patients died. For serum cystatin C and estimated GFR
      based on creatinine and cystatin C, the mortality and the hazard ratios for long
      term mortality increased from the first to the fifth quintile nearly linearly.
      The associations of serum creatinine and estimated GFR categories based on
      creatinine with long-term mortality were J-shaped. As compared with lowest
      quintile of serum cystatin C, the fifth quintile was associated with long-term
      mortality significantly also after multivariate adjustment (age, gender, initial
      stroke severity, known risk factors for stroke mortality). In contrast, in
      adjusted analysis serum creatinine and estimated GFR (CKD-EPI creatinine and CKD
      EPI creatinine/cystatin) were not associated with long-term mortality. In
      summary, serum cystatin C was independently and better associated with the risk
      of long-term mortality in patients suffering from ischemic stroke than were
      creatinine and estimated GFR using both CKD-EPI equations.

PMID- 24028542
TI  - The effect of screening doors and windows on indoor density of Anopheles
      arabiensis in south-west Ethiopia: a randomized trial.
AB  - BACKGROUND: Screening of houses might have impact on density of indoor host
      seeking Anopheles mosquitoes. A randomized trial of screening windows and doors
      with metal mesh, and closing openings on eves and walls by mud was conducted to
      assess if reduce indoor densities of biting mosquitoes. METHODS: Mosquitoes were
      collected in forty houses using Centers for Diseases Control and Prevention (CDC)
      light traps biweekly in March and April 2011. A randomization of houses into
      control and intervention groups was done based on the baseline data. Windows and
      doors of 20 houses were screened by metal mesh, and openings on the walls and
      eves closed by mud and the rest 20 houses were used as control group. Mosquitoes
      were collected biweekly in October and November 2011 from both control and
      intervention houses. A Generalized Estimating Equations (GEE) with a negative
      binomial error distribution was used to account for over dispersion of Anopheles
      arabiensis and culicine counts and repeated catches made in the same house.
      RESULTS: Screening doors and windows, and closing openings on eves and wall by
      mud reduced the overall indoor densities of An. arabiensis by 40%. The effect of
      screenings pronounced on unfed An. arabiensis by resulting 42% reduction in
      houses with interventions. The total costs for screening windows and doors, and
      to close openings on the eves and walls by mud was 7.34 USD per house.
      CONCLUSION: Screening houses reduced indoor density of An. arabiensis, and it was
      cheap and can easily incorporated into malaria vector strategies by local
      communities, but improving doors and windows fitness for screening should be
      considered during house construction to increase the efficacy of screenings.

PMID- 24028543
TI  - Fluorescent films based on molecular-gel networks and their sensing performances.
AB  - A pyrene-capped terthiophene of cholesteryl derivative (CholG-3T-Py) was
      designed, synthesized, and utilized for the fabrication of a fluorescent film.
      Unlike the commonly adopted direct-coating method, the film was fabricated by the
      physical immobilization of the fluorophore, CholG-3T-Py, onto a glass plate
      surface via preformed low-molecular-mass gelator (LMMGs)-based molecular-gel
      networks. The photophysical behavior of the film as prepared and its sensing
      performances to nitrobenzene (NB) were conducted after activation with toluene.
      It was found that the film as prepared and activated is sensitive to the presence
      of NB, and the sensing process is fully reversible. Furthermore, the effects of
      commonly found interferents, including structural analogues, raw materials, which
      are commonly used for the production of NB, and other nitroaromatics (NACs), on
      the sensing process were also tested. It was shown that only aniline and phenol
      possess slight interference. The present work not only extends the applications
      of LMMGs-based molecular gels but also provids a new approach for preparation of
      micro- and nano-structure-based fluorescent sensing films. 

PMID- 24028544
TI  - Androgen deficiency in male patients diagnosed with ANCA-associated vasculitis: a
      cause of fatigue and reduced health-related quality of life?
AB  - INTRODUCTION: Low testosterone levels in men are associated with fatigue, limited
      physical performance and reduced health-related quality of life (HRQOL); however,
      this relationship has never been assessed in patients with anti-neutrophil
      cytoplasmic antibodies (ANCA) -associated vasculitides (AAV). The aim of this
      study was to assess the prevalence of androgen deficiency and to investigate the
      role of testosterone in fatigue, limited physical condition and reduced HRQOL in
      men with AAV. METHODS: Male patients with AAV in remission were included in this
      study. Fatigue and HRQOL were assessed by the multi-dimensional fatigue inventory
      (MFI)-20 and RAND-36 questionnaires. RESULTS: Seventy male patients with a mean
      age of 59 years (SD 12) were included. Scores of almost all subscales of both
      questionnaires were significantly worse in patients compared to controls. Mean
      total testosterone and free testosterone levels were 13.8 nmol/L (SD 5.6) and 256
      pmol/L (SD 102), respectively. Androgen deficiency (defined according to
      Endocrine Society Clinical Practice Guidelines) was present in 47% of patients.
      Scores in the subscales of general health perception, physical functioning and
      reduced activity were significantly worse in patients with androgen deficiency
      compared to patients with normal androgen levels. Testosterone and age were
      predictors for the RAND-36 physical component summary in multiple linear
      regression analysis. Testosterone, age, vasculitis damage index (VDI) and C
      reactive protein (CRP) were associated with the MFI-20 subscale of general
      fatigue. CONCLUSIONS: This study showed that androgen deficiency was present in a
      substantial number of patients with AAV. Testosterone was one of the predictors
      for physical functioning and fatigue. Testosterone may play a role in fatigue,
      reduced physical performance and HRQOL in male patients with AAV.

PMID- 24028545
TI  - Relationships between flavin-containing mono-oxygenase 3 (FMO3) genotype and
      trimethylaminuria phenotype in a Japanese population.
AB  - AIM: The aim of this study was to investigate relationships between flavin
      containing mono-oxygenase 3 (FMO3) genotype and phenotype (conversion of odorous
      trimethylamine into non-odorous trimethylamine N-oxide) in a large Japanese
      cohort suffering from trimethylaminuria. METHODS: Urinary excretion of
      trimethylamine and trimethylamine N-oxide was determined for 102 volunteers with
      self-reporting symptoms of trimethylaminuria. For each we determined the sequence
      of the entire coding region, plus 1.3 kb of flanking intronic and 2.5 kb of the
      upstream region of the FMO3 gene. The affect of upstream variants on
      transcription was determined with a reporter gene assay. RESULTS: Seventy-eight
      subjects were diagnosed as suffering from trimethylaminuria, based on urinary
      excretion of <90% of total TMA as TMA N-oxide. Of these, 13 were classified as
      severe, 56 as moderate and nine as mild cases, excreting <43%, 48-70% and 73-83%
      of trimethylamine as trimethylamine N-oxide, respectively. Twenty-seven mutations
      were identified in FMO3, 15 in the coding region, of which eight abolish or
      severely impair FMO3 activity (Pro70Leu, Cys197fsX, Thr201Lys, Arg205Cys,
      Met260Val, Trp388Ter, Gln470Ter and Arg500Ter), and 12 in the upstream region.
      The mutations segregate into 19 haplotypes, including four different combinations
      of upstream mutations, each of which reduces transcriptional activity in
      comparison with the ancestral upstream sequence of FMO3. CONCLUSIONS: Comparisons
      of genotype and phenotype reveal that severe trimethylaminuria is caused by loss
      of function mutations in FMO3. For moderate and mild cases the situation is more
      complex, with most resulting from factors other than FMO3 genotype. Our results
      have implications for the diagnosis and management of the disorder.

PMID- 24028547
TI  - Hepatitis B virus reactivation after ustekinumab treatment: reply from authors.

PMID- 24028546
TI  - A multicentric randomized controlled trial on the impact of lengthening the
      interval between neoadjuvant radiochemotherapy and surgery on complete
      pathological response in rectal cancer (GRECCAR-6 trial): rationale and design.
AB  - BACKGROUND: Neoadjuvant radiochemotherapy (RCT) is now part of the armamentarium
      of cancer of the lower and middle rectum. It is recommended in current clinical
      practice prior to surgical excision if the lesion is classified T3/T4 or N+.
      Histological complete response, defined by the absence of persistent tumor cell
      invasion and lymph node (ypT0N0) after pathological examination of surgical
      specimen has been shown to be an independent prognostic factor of overall
      survival and disease-free survival. Surgical excision is usually performed
      between 6 and 8 weeks after completion of CRT and pathological complete response
      rate ranges around 12%. In retrospective studies, a lengthening of the interval
      after RCT beyond 10 weeks was found as an independent factor increasing the rate
      of pathological complete response (between 26% and 31%), with a longer disease
      free survival and without increasing the operative morbidity. The aim of the
      present study is to evaluate in 264 patients the rate of pathological complete
      response rate of rectal cancer after RCT by lengthening the time between RCT and
      surgery. METHODS/DESIGN: The current study is a multicenter randomized trial in
      two parallel groups comparing 7 and 11 weeks of delay between the end of RCT and
      cancer surgery of rectal tumors. At the end of the RCT, surgery is planified and
      randomization is performed after patient's written consent for participation. The
      histological complete response (ypT0N0) will be determined with analysis of the
      complete residual tumor and double reading by two pathologists blinded of the
      group of inclusion. Patients will be followed in clinics for 5 years after
      surgery. Participation in this trial does not change patient's management in
      terms of treatment, investigations or visits. Secondary endpoints will include
      overall and disease free survival, rate of sphincter conservation and quality of
      mesorectal excision. The number of patients needed is 264. TRIAL REGISTRATION:
      ClinicalTrial.gov: NCT01648894.

PMID- 24028548
TI  - Some recollections of Charlie Spielberger.

PMID- 24028549
TI  - Intermonomer electron transfer between the b hemes of heterodimeric cytochrome
      bc(1).
AB  - The ubihydroquinone:cytochrome c oxidoreductase, or cytochrome bc1, is a central
      component of respiratory and photosynthetic energy transduction pathways in many
      organisms. It contributes to the generation of membrane potential and proton
      gradient used for cellular energy (ATP) production. The three-dimensional
      structures of cytochrome bc1 show a homodimeric organization of its three
      catalytic subunits. The unusual architecture revived the issue of whether the
      monomers operate independently or function cooperatively during the catalytic
      cycle of the enzyme. In recent years, different genetic approaches allowed the
      successful production of heterodimeric cytochrome bc1 variants and evidenced the
      occurrence of intermonomer electron transfer between the monomers of this enzyme.
      Here we used a version of the "two-plasmid" genetic system, also described in the
      preceding paper (DOI: 10.1021/bi400560p), to study a new heterodimeric mutant
      variant of cytochrome bc1. The strain producing this heterodimeric variant
      sustained photosynthetic growth of Rhodobacter capsulatus and yielded an active
      heterodimer. Interestingly, kinetic data showed equilibration of electrons among
      the four b heme cofactors of the heterodimer, via "reverse" intermonomer electron
      transfer between the bL hemes. Both inactive homodimeric and active heterodimeric
      cytochrome bc1 variants were purified to homogeneity from the same cells, and
      purified samples were subjected to mass spectrometry analyses. The data
      unequivocally supported the idea that the cytochrome b subunits carried the
      expected mutations and their associated epitope tags. Implications of these
      findings on our interpretation of light-activated transient cytochrome b and c
      redox kinetics and the mechanism of function of a dimeric cytochrome bc1 are
      discussed with respect to the previously proposed heterodimeric Q cycle model.

PMID- 24028550
TI  - One-step assembly and targeted integration of multigene constructs assisted by
      the I-SceI meganuclease in Saccharomyces cerevisiae.
AB  - In vivo assembly of overlapping fragments by homologous recombination in
      Saccharomyces cerevisiae is a powerful method to engineer large DNA constructs.
      Whereas most in vivo assembly methods reported to date result in circular
      vectors, stable integrated constructs are often preferred for metabolic
      engineering as they are required for large-scale industrial application. The
      present study explores the potential of combining in vivo assembly of large,
      multigene expression constructs with their targeted chromosomal integration in S.
      cerevisiae. Combined assembly and targeted integration of a ten-fragment 22-kb
      construct to a single chromosomal locus was successfully achieved in a single
      transformation process, but with low efficiency (5% of the analyzed transformants
      contained the correctly assembled construct). The meganuclease I-SceI was
      therefore used to introduce a double-strand break at the targeted chromosomal
      locus, thus to facilitate integration of the assembled construct. I-SceI-assisted
      integration dramatically increased the efficiency of assembly and integration of
      the same construct to 95%. This study paves the way for the fast, efficient, and
      stable integration of large DNA constructs in S. cerevisiae chromosomes.

PMID- 24028552
TI  - Hydrophobic collapse of foldamer capsules drives picomolar-level chloride binding
      in aqueous acetonitrile solutions.
AB  - Aqueous media are competitive environments in which to perform host-guest
      chemistry, particularly when the guest is highly charged. While hydrophobic
      binding is a recognized approach to this challenge in which apolar pockets can be
      designed to recognize apolar guests in water, complementary strategies are
      required for hydrophilic anions like chloride. Here, we present evidence of such
      an alternative mechanism, used everyday by proteins yet rare for artificial
      receptors, wherein hydrophobic interactions are shown to be responsible for
      organizing and stabilizing an aryl-triazole foldamer to help extract hydrophilic
      chloride ions from increasingly aqueous solutions. Therein, a double-helical
      complex gains stability upon burial of ~80% of the pi surfaces that
      simultaneously creates a potent, solvent-excluding microenvironment for hydrogen
      bonding. The chloride's overall affinity to the duplex is substantial in 25%
      water v/v in acetonitrile (log beta2 = 12.6), and it remains strong (log beta2 =
      13.0) as the water content is increased to 50%. With the rise in predictable
      designs of abiological foldamers, this water-assisted strategy can, in principle,
      be utilized for binding other hydrophilic guests. 

PMID- 24028553
TI  - Kinetic modelling of mitochondrial translation.
AB  - Mitochondrial genome contains 13 protein coding genes, all being part of the
      oxidative phosphorylation complexes. The process of translation of these protein
      coding mRNAs in mitochondrial matrix is a good miniature model of translation in
      cytoplasm. In this work, we have simulated three phases of mitochondrial
      translation viz. initiation, elongation and termination (including ribosome
      recycling). The kinetic equations for these phases have been deduced based on the
      information available in literature. Various factors involved in the process have
      been included explicitly. Kinetic simulation was done using Octave, open source
      software. Scripts were written individually for each phase. Initiation begins
      with mitoribosome, mRNA, fMet-tRNA and initiation factors. The final product of
      the initiation script, the initiation complex, was introduced as the start point
      in the successive step, i.e. elongation. Elongation is a particular extensive
      process where the various aminoacyl-tRNAs already present in the matrix check for
      matching with the triplet codon in A-site of mitoribosome. This script consists
      of two parts: one with the time behaviour of the factors involved in the
      molecular process (using ordinary differential equation solver) and the other
      including the reading of triplet codon on the mRNA and incorporating the
      corresponding aminoacyl-tRNA, and then at each step elongating the peptide chain
      (using loops and conditions). The peptide chain thus formed in the elongation
      step (in the loops and conditions segment) was released in the termination step.
      This was followed by mitoribosome recycling where the mitoribosome reached the
      native state and was ready for the next cycle of translation.

PMID- 24028551
TI  - Contrasted evolutionary histories of two Toll-like receptors (Tlr4 and Tlr7) in
      wild rodents (MURINAE).
AB  - BACKGROUND: In vertebrates, it has been repeatedly demonstrated that genes
      encoding proteins involved in pathogen-recognition by adaptive immunity (e.g.
      MHC) are subject to intensive diversifying selection. On the other hand, the role
      and the type of selection processes shaping the evolution of innate-immunity
      genes are currently far less clear. In this study we analysed the natural
      variation and the evolutionary processes acting on two genes involved in the
      innate-immunity recognition of Microbe-Associated Molecular Patterns (MAMPs).
      RESULTS: We sequenced genes encoding Toll-like receptor 4 (Tlr4) and 7 (Tlr7),
      two of the key bacterial- and viral-sensing receptors of innate immunity, across
      23 species within the subfamily Murinae. Although we have shown that the
      phylogeny of both Tlr genes is largely congruent with the phylogeny of rodents
      based on a comparably sized non-immune sequence dataset, we also identified
      several potentially important discrepancies. The sequence analyses revealed that
      major parts of both Tlrs are evolving under strong purifying selection, likely
      due to functional constraints. Yet, also several signatures of positive selection
      have been found in both genes, with more intense signal in the bacterial-sensing
      Tlr4 than in the viral-sensing Tlr7. 92% and 100% of sites evolving under
      positive selection in Tlr4 and Tlr7, respectively, were located in the
      extracellular domain. Directly in the Ligand-Binding Region (LBR) of TLR4 we
      identified two rapidly evolving amino acid residues and one site under positive
      selection, all three likely involved in species-specific recognition of
      lipopolysaccharide of gram-negative bacteria. In contrast, all putative sites of
      LBRTLR7 involved in the detection of viral nucleic acids were highly conserved
      across rodents. Interspecific differences in the predicted 3D-structure of the
      LBR of both Tlrs were not related to phylogenetic history, while analyses of
      protein charges clearly discriminated Rattini and Murini clades. CONCLUSIONS: In
      consequence of the constraints given by the receptor protein function purifying
      selection has been a dominant force in evolution of Tlrs. Nevertheless, our
      results show that episodic diversifying parasite-mediated selection has shaped
      the present species-specific variability in rodent Tlrs. The intensity of
      diversifying selection was higher in Tlr4 than in Tlr7, presumably due to
      structural properties of their ligands.

PMID- 24028554
TI  - Exploring motivation and confidence in taking prescribed medicines in coexisting
      diseases: a qualitative study.
AB  - AIMS AND OBJECTIVES: To explore the motivation and confidence of people with
      coexisting diabetes, chronic kidney disease (CKD) and hypertension to take their
      medicines as prescribed. BACKGROUND: These comorbidities are major contributors
      to disease burden globally. Self-management of individuals with these coexisting
      diseases is much more complicated than that of those with single diseases and is
      critical for improved health outcomes. DESIGN: Motivational interviewing
      telephone calls were made with participants with coexisting diabetes, CKD and
      hypertension. METHODS: Patients aged >=18 years with diabetes, CKD and systolic
      hypertension were recruited from outpatient clinics of an Australian metropolitan
      hospital between 2008-2009. An average of four motivational interviewing
      telephone calls was made with participants (n = 39) in the intervention arm of a
      randomised controlled trial. Data were thematically analysed using the modified
      Health Belief Model as a framework. RESULTS: Participants' motivation and
      confidence in taking prescribed medicines was thwarted by complex medicine
      regimens and medical conditions. Participants wanted control over their health
      and developed various strategies to confront threats to health. The perceived
      barriers of taking recommended health action outweighed the benefits of taking
      medicines as prescribed and were primarily related to copious amounts of
      medicines. CONCLUSION: Taking multiple prescribed medicines in coexisting
      diabetes, CKD and hypertension is a perpetual vocation with major psychosocial
      effects. Participants were overwhelmed by the number of medicines that they were
      required to take. The quest for personal control of health, fear of the future
      and the role of stress and gender in chronic disease management have been
      highlighted. Participants require supportive emotional interventions to self
      manage their multiple medicines on a daily basis. RELEVANCE TO CLINICAL PRACTICE:
      Reducing the complexity of medicine regimens in coexisting diseases is paramount.
      Individualised psychosocial approaches that address the emotional needs of
      patients with regular follow-up and feedback are necessary for optimal chronic
      disease self-management.

PMID- 24028555
TI  - Spectroscopy of cold LiCa molecules formed on helium nanodroplets.
AB  - We report on the formation of mixed alkali-alkaline earth molecules (LiCa) on
      helium nanodroplets and present a comprehensive experimental and theoretical
      study of the ground and excited states of LiCa. Resonance enhanced multiphoton
      ionization time-of-flight (REMPI-TOF) spectroscopy and laser induced fluorescence
      (LIF) spectroscopy were used for the experimental investigation of LiCa from
      15000 to 25500 cm(-1). The 4(2)Sigma(+) and 3(2)Pi states show a vibrational
      structure accompanied by distinct phonon wings, which allows us to determine
      molecular parameters as well as to study the interaction of the molecule with the
      helium droplet. Higher excited states (4(2)Pi, 5(2)Sigma(+), 5(2)Pi, and
      6(2)Sigma(+)) are not vibrationally resolved and vibronic transitions start to
      overlap. The experimental spectrum is well reproduced by high-level ab initio
      calculations. By using a multireference configuration interaction (MRCI)
      approach, we calculated the 19 lowest lying potential energy curves (PECs) of the
      LiCa molecule. On the basis of these calculations, we could identify previously
      unobserved transitions. Our results demonstrate that the helium droplet isolation
      approach is a powerful method for the characterization of tailor-made alkali
      alkaline earth molecules. In this way, important contributions can be made to the
      search for optimal pathways toward the creation of ultracold alkali-alkaline
      earth ground state molecules from the corresponding atomic species. Furthermore,
      a test for PECs calculated by ab initio methods is provided. 

PMID- 24028556
TI  - Effect of Al3+ co-doping on the dopant local structure, optical properties, and
      exciton dynamics in Cu+-doped ZnSe nanocrystals.
AB  - The dopant local structure and optical properties of Cu-doped ZnSe (ZnSe:Cu) and
      Cu and Al co-doped ZnSe (ZnSe:Cu,Al) nanocrystals (NCs) were studied with an
      emphasis on understanding the impact of introducing Al as a co-dopant. Quantum
      confined NCs with zinc blende crystal structure and particle size of 6 +/- 0.6 A
      were synthesized using a wet chemical route. The local structure of the Cu
      dopant, studied by extended X-ray absorption fine structure, indicated that Cu in
      ZnSe:Cu NCs occupies a site that is neither substitutional nor interstitial and
      is adjacent to a Se vacancy. Additionally, we estimated that approximately 25 +/-
      8% of Cu was located on the surface of the NC. Al(3+) co-doping aids in Cu doping
      by accounting for the charge imbalance originated by Cu(+) doping and
      consequently reduces surface Cu doping. The Cu ions remain distorted from the
      center of the tetrahedron to one of the triangular faces. The lifetime of the
      dopant-related photoluminescence was found to increase from 550 +/- 60 to 700 +/-
      60 ns after Al co-doping. DFT calculations were used to obtain the density of
      states of a model system to help explain the optical properties and dynamics
      processes observed. This study demonstrates that co-doping using different
      cations with complementary oxidation states is an effective method to enhance
      optical properties of doped semiconductor NCs of interest for various photonics
      applications. 

PMID- 24028557
TI  - Defining soldier equipment trade space: load effects on combat marksmanship and
      perception-action coupling.
AB  - Soldier equipment compromises task performance as temporal constraints during
      critical situations and load increase inertial and interactive forces during
      movement. Methods are necessary to optimise equipment that relate task
      performance to underlying coordination and perception-action coupling. Employing
      ecological task analysis and methods from dynamical systems theory, equipment
      load and coordination was examined during two sub-tasks embedded in combat
      performance, threat discrimination and dynamic marksmanship. Perception-action
      coupling was degraded with load during threat discrimination, leading to delays
      in functional reaction time. Reduced speed and accuracy during dynamic
      marksmanship under load was related to disrupted segmental coordination and
      adaptability during postural transitions between targets. These results show how
      reduced performance under load relates to coordination changes and perception
      action coupling. These changes in functional capability are directly related to
      soldier survivability in combat. The methods employed may aid equipment design
      towards more optimised performance by modifying equipment or its distribution on
      humans. 

PMID- 24028558
TI  - Which emergency medical dispatch codes predict high prehospital nontransport
      rates in an urban community?
AB  - BACKGROUND: The Medical Priority Dispatch System (MPDS) is a commonly used
      computer-based emergency medical dispatch (EMD) system that is widely used to
      prioritize 9-1-1 calls and optimize resource allocation. There are five major
      priority classes used to dispatch 9-1-1 calls in the San Francisco System; Alpha
      codes are the lowest priority (lowest expected acuity) and Echo are the highest
      priority. OBJECTIVE: We sought to determine which MPDS dispatch codes are
      associated with high prehospital nontransport rates (NTRs). METHODS: All unique
      MPDS call categories from 2009 in a highly urbanized, two-tier advanced life
      support (ALS) system were sorted according to highest NTRs. There are many
      reasons for nontransport, such as "gone on arrival," and "patient denied
      transport." Those categories with greater than 100 annual calls were further
      evaluated. MPDS groups that included multiple categories with NTRs exceeding 25%
      were then identified and each category was analyzed. Results. EMS responded to a
      total of 81,437 calls in 2009, of which 18,851 were not transported by EMS. The
      majority of the NTRs were found among "cardiac/ respiratory arrest/death,"
      "assault/sexual assaults," "unknown problem/man down," "traffic/transportation
      accidents," and "unconscious/fainting." "Cardiac or respiratory arrest/death 
      obvious death" (9B1) had the highest overall nontransport rate, 99.25% (1/134),
      most likely due to declaration of death. "Unknown problem -man down -medical
      alert notification" had the second highest NTR, 67.22% (138/421). However, Echo
      priority codes had the highest overall nontransport rates (45.45%) and Charlie
      had the lowest (13.84%). CONCLUSIONS: The nontransport rates of individual MPDS
      categories vary considerably and should be considered in any system design. We
      identified 52 unique call categories to have a 25% or greater NTR, 18 of which
      exceeded 40%. The majority of NTRs occurred among the "cardiac/respiratory
      arrest/death," "assault/sexual assaults," "unknown problem/man down,"
      "traffic/transportation accidents," and "unconscious/fainting" categories. The
      higher the priority code within each subset (AB vs. CDE), the less likely the
      patient was to be transported. Charlie priority codes had a lower NTR than Delta,
      and Delta was lower than Echo. Charlie codes were therefore the strongest
      predictors of hospital transport, while Echo codes (highest priority) were those
      with the highest nontransport rates and were the worst predictors of hospital
      transport in the emergent subset.

PMID- 24028559
TI  - The edentulous ridge expansion (ERE) technique an experimental study in the dog.
AB  - OBJECTIVE: To compare the healing and bony crest resorption at implants installed
      conventionally or applying an edentulous ridge expansion (ERE) technique in the
      maxilla. MATERIAL AND METHODS: In six Labrador dogs, the first and second
      maxillary incisors were extracted bilaterally. In the left side of the maxilla
      (Test), the flaps were elevated and the buccal plate of the alveoli and septa was
      removed. After 3 months of healing, partial-thickness (split) flaps were
      dissected and the residual alveolar bone was exposed. In the right side of the
      maxilla, an implant was installed conventionally (Type IV; Control) while, in the
      left side, the ERE technique was adopted. Hence, an expansion of the buccal bony
      crest was obtained, and the implant was subsequently installed (Test). After 3
      months of healing, biopsies were obtained and ground sections were prepared for
      histological analyses. RESULTS: A buccal vertical resorption of the bony crest of
      2.2 +/- 1.2 mm and 1.6 +/- 0.7 mm was found at the test and control sites,
      respectively. The difference, however, did not reach statistical significance.
      The coronal level of osseointegration at the buccal aspect was located at 3.1 +/-
      1.0 mm and 2.2 +/- 0.7 mm from the implant shoulder at the test and control
      sites, respectively, the difference being statistically significant. The mean
      values of the mineralized bone-to-implant contact (MBIC%) ranged from 43% to 48%
      at the buccal and lingual sites. No differences reached statistical significance.
      CONCLUSIONS: Implants installed by applying an ERE technique may osseointegrate
      similarly to conventional implant installation. However, vertical and horizontal
      resorption of the displaced buccal bony wall occurred as well.

PMID- 24028561
TI  - Effect of 8-oxoguanine on DNA structure and deformability.
AB  - 8-Oxoguanine (oxoG) is an abundant product of oxidative DNA damage. It is removed
      by repair glycosylases, but exactly how the enzymes recognize oxoG in the large
      surplus of undamaged bases is not fully understood. The lesion may induce changes
      in the properties of naked DNA that facilitate the recognition. In this work, we
      assess the effect of oxoG on DNA structure and mechanical deformability. We
      performed extensive unrestrained, atomic resolution molecular dynamics
      simulations to parametrize a nonlocal, rigid base mechanical model of DNA. Our
      data indicate that oxoG induces unwinding of the base pair step at the 5'-side of
      the lesion. This brings the damaged DNA closer to its conformation in the initial
      complex with bacterial glycosylase MutM. The untwisting is partially caused by
      different BII substate populations and is further enhanced by the base-sugar
      repulsion within oxoG. On the other hand, our analysis shows that damaged and
      undamaged DNA have very similar harmonic stiffness. These results suggest an
      indirect readout component of the MutM-DNA initial complex formation. They also
      help one to understand the effect of oxoG on the formation of nucleosomes and
      looped gene regulatory complexes. 

PMID- 24028560
TI  - Coxiella burnetii exploits host cAMP-dependent protein kinase signalling to
      promote macrophage survival.
AB  - Intracellular bacterial pathogens often subvert apoptosis signalling to regulate
      survival of their host cell, allowing propagation of the bacterial population.
      Coxiella burnetii, the intracellular agent of human Q fever, inhibits host cell
      apoptosis through several mechanisms, including prevention of mitochondrial
      cytochrome c release, triggering of an anti-apoptotic transcriptional programme,
      and activation of pro-survival kinases. To control host cell survival, C.
      burnetii delivers effector proteins to the eukaryotic cytosol using a specialized
      Dot/Icm type IV secretion system (T4SS). Effectors are predicted to regulate
      activity of pro-survival host signalling proteins, such as Akt and cAMP-dependent
      protein kinase (PKA), to control infection. Here, we show that host PKA activity
      is required for C. burnetii inhibition of macrophage apoptosis. PKA is activated
      during infection and inhibits activity of the pro-apoptotic protein Bad via
      phosphorylation. Bad is also phosphorylated at an Akt-specific residue,
      indicating C. burnetii uses two kinases to fully inactivate Bad. Additionally,
      Bad and the tethering protein 14-3-3beta colocalize at the C. burnetii
      parasitophorous vacuole (PV) membrane during infection, an event predicted to
      alter Bad promotion of apoptosis. Inhibiting PKA activity prevents Bad
      recruitment to the PV, but the protein is retained at the membrane during
      induction of apoptosis. Finally, PKA regulatory subunit I (RI) traffics to the PV
      membrane in a T4SS-dependent manner, suggesting a C. burnetii effector(s)
      regulates PKA-dependent activities. This study is the first to demonstrate
      subversion of host PKA activity by an intracellular bacterial pathogen to prevent
      apoptosis and survive within macrophages. 

PMID- 24028562
TI  - Abdominal adiposity and caregiver recall of healthcare provider identification of
      child overweight in the United States, 2001-2010.
AB  - BACKGROUND: A minority of overweight or obese children are identified as such by
      a healthcare provider (HCP). The aim of this study was to examine characteristics
      of caregiver-reported HCP identification of overweight or obesity and whether it
      is associated with children's waist circumference (WC). METHODS: This was an
      observational study using a nationally representative sample of 14,694 children
      (2-15 years of age) from the 2001-2010 National Health and Nutrition Examination
      Survey. Proxy respondents (i.e., caregivers) for 4906 overweight or obese
      (BMI>=85th percentile) children reported whether an HCP had ever told them that
      their child was overweight. Multi-variable logistic regression analyses were used
      to examine associations between reported HCP identification of overweight and
      child sociodemographic and anthropometric characteristics. RESULTS: Over 75% of
      caregivers of overweight or obese children did not recall being notified of their
      child's weight status by an HCP, though this proportion has decreased over the
      past decade. A significant WC by weight status interaction indicated abdominal
      adiposity was positively associated with reported HCP identification for obese
      children, but not for overweight children. CONCLUSIONS: Lower levels of reported
      HCP identification were observed for overweight children, compared to obese
      children; among obese children, those with lower levels of abdominal adiposity
      were less likely to be identified as overweight by an HCP, according to
      caregivers. Reasons for this finding remain unclear. Providers may be relying on
      a child's appearance, rather than universally screening all patients for
      overweight. Additionally, a variety of parent and provider characteristics may
      influence weight-related communications and caregiver recall of such information.

PMID- 24028563
TI  - Parents and pediatric weight management attrition: experiences and
      recommendations.
AB  - BACKGROUND: One of the most frequently cited challenges faced by pediatric weight
      management programs/clinics is attrition, with many studies reporting rates
      greater than 50%. Few studies have evaluated parental perspectives on
      recommendations for weight-management treatment enhancement. The aim of this
      study was to elicit perspectives on areas for improvement, discussions with staff
      about discontinuation, and potentially modifiable aspects of attrition from
      parents who prematurely discontinued stage 3 pediatric weight management
      treatment. METHODS: This study was performed as a semistructured interview as
      part of a telephone survey assessing reasons for attrition. RESULTS: Interviews
      were performed with 147 parents of children who attended programs/clinics at 13
      children's hospitals participating in the National Association of Children's
      Hospitals and Related Institutions (now Children's Hospital Association) FOCUS on
      a Fitter Future II collaborative. The majority of parents (65%) denied talking to
      staff about their decisions to stop coming. When describing what could have been
      done to retain families, parents most frequently discussed changing logistics
      (e.g., hours and locations). Parents described changes in logistics and
      components (i.e., nutrition education, exercise, and behavior education/support)
      when asked what would work best for their family for pediatric weight management.
      CONCLUSIONS: Parental responses appeared to express frustration about flexibility
      with appointment times and treatment locations. The most frequently desired
      components were those traditionally offered by stage 3 pediatric weight
      management programs/clinics, and this may suggest a need for treatment delivery
      of these components to be more individualized. Additional discussion with
      families about their desire to discontinue treatment may provide a timely
      opportunity to address this need.

PMID- 24028564
TI  - Physical activity and screen-media-related parenting practices have different
      associations with children's objectively measured physical activity.
AB  - BACKGROUND: Children's physical activity (PA) is inversely associated with
      children's weight status. Parents may be an important influence on children's PA
      by restricting sedentary time or supporting PA. The aim of this study was to
      investigate the association of PA and screen-media-related [television (TV) and
      videogame] parenting practices with children's PA. METHODS: Secondary analyses of
      baseline data were performed from an intervention with 9- to 12-year-olds who
      received active or inactive videogames (n=83) to promote PA. Children's PA was
      assessed with 1 week of accelerometry at baseline. Parents reported their PA, TV,
      and videogame parenting practices and child's bedroom screen-media availability.
      Associations were investigated using Spearman's partial correlations and linear
      regressions. RESULTS: Although several TV and videogame parenting practices were
      significantly intercorrelated, only a few significant correlations existed
      between screen-media and PA parenting practices. In linear regression models,
      restrictive TV parenting practices were associated with greater child sedentary
      time (p=0.03) and less moderate-to-vigorous PA (MVPA; p=0.01). PA logistic
      support parenting practices were associated with greater child MVPA (p=0.03).
      Increased availability of screen-media equipment in the child's bedroom was
      associated with more sedentary time (p=0.02) and less light PA (p=0.01) and MVPA
      (p=0.05) in all three models. CONCLUSION: In this cross-sectional sample,
      restrictive screen-media and supportive PA parenting practices had opposite
      associations with children's PA. Longitudinal and experimental child PA studies
      should assess PA and screen-media parenting separately to understand how parents
      influence their child's PA behaviors and whether the child's baseline PA or
      screen media behaviors affect the parent's use of parenting practices.
      Recommendations to remove screens from children's bedrooms may also affect their
      PA.

PMID- 24028565
TI  - Controlled iontophoretic transport of huperzine A across skin in vitro and in
      vivo: effect of delivery conditions and comparison of pharmacokinetic models.
AB  - The aim of this study was to investigate constant current anodal iontophoresis of
      Huperzine A (HupA) in vitro and in vivo and hence to evaluate the feasibility of
      using electrically assisted delivery to administer therapeutic amounts of the
      drug across the skin for the treatment of Alzheimer's disease. Preliminary
      experiments were performed using porcine and human skin in vitro. Stability
      studies demonstrated that HupA was not degraded upon exposure to epidermis or
      dermis for 12 h and that it was also stable in the presence of an electric
      current (0.5 mA . cm(-2)). Passive permeation of HupA (2 mM) was minimal (1.1 +/-
      0.1 MUg . cm(-2)); iontophoresis at 0.15, 0.3, and 0.5 mA . cm(-2) produced 106-,
      134-, and 184-fold increases in its transport across the skin. Surprisingly,
      despite the use of a salt bridge to isolate the formulation compartment from the
      anodal chamber, which contained 133 mM NaCl, iontophoresis of HupA was shown to
      increase linearly with its concentration (1, 2, and 4 mM in 25 mM MES, pH 5.0)
      (r(2) = 0.99). This was attributed to the low ratio of drug to Cl- (in the skin
      and in the receiver compartment) which competed strongly to carry current, its
      depletion, and to possible competition from the zwitterionic MES. Co
      iontophoresis of acetaminophen confirmed that electromigration was the dominant
      electrotransport mechanism. Total delivery across human and porcine skin was
      found to be statistically equivalent (243.2 +/- 33.1 and 235.6 +/- 13.7 MUg . cm(
      2), respectively). Although the transport efficiency was ~ 1%, the iontophoretic
      delivery efficiency (i.e., the fraction of the drug load delivered) was extremely
      high, in the range of 46-81% depending on the current density. Cumulative
      permeation of HupA from a Carbopol gel formulation after iontophoresis for 6 h at
      0.5 mA . cm(-2) was less than that from solution (135.3 +/- 25.2 and 202.9 +/-
      5.2 MUg . cm(-2), respectively) but sufficient for therapeutic delivery.
      Pharmacokinetic parameters were determined in male Wistar rats in vivo (4 mM
      HupA; 0.5 mA . cm(-2) for 5 h with Ag/AgCl electrodes) using two-compartment
      models with either constant or time-variant input rates. A superior fit was
      obtained using the time-variant model, and the input rate in vivo was
      significantly greater than that in vitro. Based on these results and the known
      pharmacokinetics, it was estimated that therapeutic amounts of HupA could be
      delivered for the treatment of Alzheimer's disease using a reasonably sized
      patch.

PMID- 24028566
TI  - Late failure of a split-thickness skin graft in the setting of homozygous factor
      V Leiden mutation: a case report and correlative animal model from the Wound
      Etiology and Healing (WE-HEAL) study.
AB  - We present the case of a 53-year-old Caucasian male smoker with remote history of
      left lower extremity deep venous thrombosis (DVT) and a strong family history of
      thrombosis, who presented to the Center for Wound Healing at MedStar Georgetown
      University Hospital with spontaneous left leg ulceration. Prothrombotic
      evaluation showed homozygosity for the factor V Leiden (FVL) mutation.
      Therapeutic anticoagulation was commenced with warfarin (Coumadin(r)) and the
      patient underwent successful debridement and Apligraf(r) followed by split
      thickness skin graft (STSG) of two wounds. He had an uneventful postoperative
      course and on the 27th postoperative day the grafts were 95% intact. However, by
      postoperative day 41 there was 10% graft loss, and over the subsequent 2 weeks
      both grafts necrosed. On further questioning, it transpired that the patient had
      discontinued his warfarin on postoperative day 37 because he thought that it was
      no longer necessary. The patient is enrolled in the Wound Etiology and Healing
      (WE-HEAL) study, and at the time of the original graft, residual skin fragments
      from the STSG were transplanted onto a nude mouse for development of an animal
      model of wound healing. The mouse graft was successful and was harvested at
      postoperative day 87 for pathological examination. We review the mechanisms by
      which prothrombotic states, particularly FVL mutation, can contribute to skin
      graft failure and delayed wound healing. This case highlights the importance of
      considering prothrombotic conditions in patients with spontaneous leg ulcerations
      and the impact of therapeutic anticoagulation on healing. It further allows us to
      demonstrate the efficacy of the animal model in which residual fragments of STSG
      tissue are utilised for transplant onto nude mice for manipulation in the
      laboratory. 

PMID- 24028567
TI  - Predicting persistent inflammatory arthritis amongst early arthritis clinic
      patients in the UK: is musculoskeletal ultrasound required?
AB  - INTRODUCTION: Analyses of large clinical datasets from early arthritis cohorts
      permit the development of algorithms that may be used for outcome prediction in
      individual patients. The value added by routine use of musculoskeletal ultrasound
      (MSUS) in an early arthritis setting, as a component of such predictive
      algorithms, remains to be determined. METHODS: The authors undertook a
      retrospective analysis of a large, true-to-life, observational inception cohort
      of early arthritis patients in Newcastle upon Tyne, UK, which included patients
      with inflammatory arthralgia but no clinically swollen joints. A pragmatic, 10
      minute MSUS assessment protocol was developed, and applied to each of these
      patients at baseline. Logistic regression was used to develop two "risk metrics"
      that predicted the development of a persistent inflammatory arthritis (PIA), with
      or without the inclusion of MSUS parameters. RESULTS: A total of 379 enrolled
      patients were assigned definitive diagnoses after >=12 months follow-up (median
      28 months), of whom 162 (42%) developed a persistent inflammatory arthritis. A
      risk metric derived from 12 baseline clinical and serological parameters alone
      had an excellent discriminatory utility with respect to an outcome of PIA (area
      under receiver operator characteristic (ROC) curve 0.91; 95% CI 0.88 to 0.94).
      The discriminatory utility of a similar metric, which incorporated MSUS
      parameters, was not significantly superior (area under ROC curve 0.91; 95% CI
      0.89 to 0.94). Neither did this approach identify an added value of MSUS over the
      use of routine clinical parameters in an algorithm for discriminating PIA
      patients whose outcome diagnosis was rheumatoid arthritis (RA). CONCLUSIONS: MSUS
      use as a routine component of assessment in an early arthritis clinic did not add
      substantial discriminatory value to a risk metric for predicting PIA.

PMID- 24028568
TI  - Structural insights into the hydrolysis and polymorphism of methotrexate
      polyglutamate by zebrafish gamma-glutamyl hydrolase.
AB  - gamma-Glutamyl hydrolases (gammaGH) catalyze the hydrolysis of gamma-linked
      glutamate residues from the polyglutamyl of folates and antifolates, such as
      methotrexate (MTX), a widely used anticancer drug. We describe the first crystal
      structures of the endopeptidase-type gammaGH (zgammaGH) from zebrafish and the
      mutant complexes with MTX(Glu)5 and hydrolyzed MTX(Glu)1, revealing the complete
      set of key residues involved in hydrolysis as well as the substrate-binding
      subsites (-1 to +2). The side chain of Phe20 and the 6-methylpterin ring of
      MTX(Glu)5 invoke pi-pi interactions to promote distinct concerted conformational
      alterations involving ~90 degrees  rotations in the complexes with the zgammaGH
      C108A and zgammaGH-H218N mutant proteins. The structural geometries of the
      MTX(Glu)5 and hydrolyzed MTX(Glu)1 in the mutant complexes differ significantly
      from those of the previously known MTX(Glu)1, providing polymorphic information.
      Together with the structural comparison and the activity analysis, these results
      shed light on the catalytic mechanism and substrate recognition of zgammaGH and
      other gamma-glutamyl hydrolases. 

PMID- 24028569
TI  - Is IL-33 useful to detect early stage of renal failure?
AB  - IL-33 is a proinflammatory cytokine that is a member of IL-1 family. Previously
      the effect of IL-33 on kidney injury is showed in animal models. In this study,
      we searched if we can use IL-33 to show the early stage of kidney injury in
      diabetic patients. Three groups are identified: 26 patients in Group 1: Healthy
      group, that do not have any chronic diseases and not taking any medication; 42
      patients in Group 2: DM (diabetes mellitus) group without any known kidney
      disease and with normal kidney functions; 32 patients in Group 3: DM + MA
      (microalbuminuria) group that are assumed to have nephropathy. IL-33 level of DM
      patient group is greater than healthy group; also IL-33 level of DM + MA patient
      group is greater than healthy group; but there is not any difference between DM
      and DM + MA group. The increase in IL-33 levels in diabetic nephropathy is not
      associated with kidney injury but the increase could be resulting because of
      diabetes. So IL-33 cannot be used in early recognition of diabetic nephropathy.

PMID- 24028570
TI  - Culture-adapted Plasmodium falciparum isolates from UK travellers: in vitro drug
      sensitivity, clonality and drug resistance markers.
AB  - BACKGROUND: The screening of lead compounds against in vitro parasite cultures is
      an essential step in the development of novel anti-malarial drugs, but currently
      relies on laboratory parasite lines established in vitro during the last century.
      This study sought to establish in continuous culture a series of recent
      Plasmodium falciparum isolates to represent the current parasite populations in
      Africa, all of which are now exposed to artemisinin combination therapy. METHODS:
      Pre-treatment P. falciparum isolates were obtained in EDTA, and placed into
      continuous culture after sampling of DNA. One post-treatment blood sample was
      also collected for each donor to monitor parasite clonality during clearance in
      vivo. IC50 estimates were obtained for 11 anti-malarial compounds for each
      established parasite line, clonal multiplicity measured in vivo and in vitro, and
      polymorphic sites implicated in parasite sensitivity to drugs were investigated
      at the pfmdr1, pfcrt, pfdhfr, pfdhps and pfap2mu loci before and after treatment,
      and in the cultured lines. RESULTS: Plasmodium falciparum isolates from seven
      malaria patients with recent travel to three West African and two East African
      countries were successfully established in long-term culture. One of these,
      HL1211, was from a patient with recrudescent parasitaemia 14 days after a full
      course of artemether-lumefantrine. All established culture lines were shown to be
      polyclonal, reflecting the in vivo isolates from which they were derived, and at
      least two lines reliably produce gametocytes in vitro. Two lines displayed high
      chloroquine IC50 estimates, and carried the CVIET haplotype at codons 72-76,
      whereas the remaining five lines carried the CVMNK haplotype and were sensitive
      in vitro. All were sensitive to the endoperoxides dihydroartemisinin and OZ277,
      but IC50 estimates for lumefantrine varied, with the least sensitive parasites
      carrying pfmdr1 alleles encoding Asn at codon 86. CONCLUSIONS: This study
      describes the establishment in continuous culture, in vitro drug sensitivity
      testing and molecular characterization of a series of multiclonal P. falciparum
      isolates taken directly from UK malaria patients following recent travel to
      various malaria-endemic countries in Africa. These "HL" isolates are available as
      an open resource for studies of drug response, antigenic diversity and other
      aspects of parasite biology.

PMID- 24028573
TI  - Electrospun ZnO nanowire plantations in the electron transport layer for high
      efficiency inverted organic solar cells.
AB  - Inverted bulk heterojunction organic solar cells having device structure
      ITO/ZnO/poly(3-hexylthiophene) (P3HT):[6,6]-phenyl C61 butyric acid methyl ester
      (PCBM) /MoO3/Ag were fabricated with high photoelectric conversion efficiency and
      stability. Three types of devices were developed with varying electron
      transporting layer (ETL) ZnO architecture. The ETL in the first type was a sol
      gel-derived particulate film of ZnO, which in the second and third type contained
      additional ZnO nanowires of varying concentrations. The length of the ZnO
      nanowires, which were developed by the electrospinning technique, extended up to
      the bulk of the photoactive layer in the device. The devices those employed a
      higher loading of ZnO nanowires showed 20% higher photoelectric conversion
      efficiency (PCE), which mainly resulted from an enhancement in its fill factor
      (FF). Charge transport characteristic of the device were studied by transient
      photovoltage decay and charge extraction by linearly increasing voltage
      techniques. Results show that higher PCE and FF in the devices employed ZnO
      nanowire plantations resulted from improved charge collection efficiency and
      reduced recombination rate. 

PMID- 24028572
TI  - Associations between depression and different measures of obesity (BMI, WC, WHtR,
      WHR).
AB  - BACKGROUND: Growing evidence suggests that abdominal obesity is a more important
      risk factor for the prognosis of cardiovascular and metabolic diseases than BMI.
      Somatic-affective symptoms of depression have also been linked to cardiovascular
      risk. The relationship between obesity and depression, however, has remained
      contradictory. Our aim was therefore to relate body mass index (BMI) and
      different measures for abdominal obesity (waist circumference, WC, waist-to-hip
      ratio, WHR, waist-to-height ratio, WHtR) to somatic vs. cognitive-affective
      symptoms of depression. METHODS: In a cross-sectional population based study,
      data on the first N = 5000 participants enrolled in the Gutenberg Health Study
      (GHS) are reported. To analyze the relationship between depression and obesity,
      we computed linear regression models with the anthropometric measure (BMI, WC,
      WHR, WHtR) as the dependent variable and life style factors, cardiovascular risk
      factors and psychotropic medications as potential confounders of
      obesity/depression. RESULTS: We found that only the somatic, but not the
      cognitive-affective symptoms of depression are consistently positively associated
      with anthropometric measures of obesity. CONCLUSIONS: We could demonstrate that
      the somatic-affective symptoms of depression rather than the cognitive-affective
      symptoms are strongly related to anthropometric measures. This is also true for
      younger obese starting at the age of 35 years. Our results are in line with
      previous studies indicating that visceral adipose tissue plays a key role in the
      relationship between obesity, depression and cardiovascular disease.

PMID- 24028571
TI  - Brachydactyly E: isolated or as a feature of a syndrome.
AB  - Brachydactyly (BD) refers to the shortening of the hands, feet or both. There are
      different types of BD; among them, type E (BDE) is a rare type that can present
      as an isolated feature or as part of more complex syndromes, such as:
      pseudohypopthyroidism (PHP), hypertension with BD or Bilginturan BD (HTNB), BD
      with mental retardation (BDMR) or BDE with short stature, PTHLH type. Each
      syndrome has characteristic patterns of skeletal involvement. However,
      brachydactyly is not a constant feature and shows a high degree of phenotypic
      variability. In addition, there are other syndromes that can be misdiagnosed as
      brachydactyly type E, some of which will also be discussed. The objective of this
      review is to describe some of the syndromes in which BDE is present, focusing on
      clinical, biochemical and genetic characteristics as features of differential
      diagnoses, with the aim of establishing an algorithm for their differential
      diagnosis. As in our experience many of these patients are recruited at
      Endocrinology and/or Pediatric Endocrinology Services due to their short stature,
      we have focused the algorithm in those steps that could mainly help these
      professionals. 

PMID- 24028574
TI  - Biofilm development and the dynamics of preferential flow paths in porous media.
AB  - A two-dimensional pore-scale numerical model was developed to evaluate the
      dynamics of preferential flow paths in porous media caused by bioclogging. The
      liquid flow and solute transport through the pore network were coupled with a
      biofilm model including biomass attachment, growth, decay, lysis, and detachment.
      Blocking of all but one flow path was obtained under constant liquid inlet flow
      rate and biomass detachment caused by shear forces only. The stable flow path
      formed when biofilm detachment balances growth, even with biomass weakened by
      decay. However, shear forces combined with biomass lysis upon starvation could
      produce an intermittently shifting location of flow channels. Dynamic flow
      pathways may also occur when combined liquid shear and pressure forces act on the
      biofilm. In spite of repeated clogging and unclogging of interconnected pore
      spaces, the average permeability reached a quasi-constant value. Oscillations in
      the medium permeability were more pronounced for weaker biofilms. 

PMID- 24028575
TI  - Drosophila as a screening tool to study human neurodegenerative diseases.
AB  - In an aging society, research involving neurodegenerative disorders is of
      paramount importance. Over the past few years, research on Alzheimer's and
      Parkinson's diseases has made tremendous progress. Experimental studies, however,
      rely mostly on transgenic animal models, preferentially using mice. Although
      experiments on mice have enormous advantages, they also have some inherent
      limitations, some of which can be overcome by the use of Drosophila melanogaster
      as an experimental animal. Among the major advantages of using the fly is its
      small genome, which can also be modified very easily. The fact that its genome
      lends itself to diverse alterations (e. g. mutagenesis, transposons) has made the
      fly a useful organism to perform large-scale and genome-wide screening
      approaches. This has opened up an entirely new field of experimental research
      aiming to elucidate genetic interactions and screen for modifiers of disease
      processes in vivo. Here, we provide a brief overview of how flies can be used to
      analyze molecular mechanisms underlying human neurodegenerative diseases.

PMID- 24028576
TI  - Alcohols are inhibitors of Saccharomyces cerevisiae multidrug-resistance pumps
      Pdr5p and Snq2p.
AB  - The effect of alcohols on cell membrane proteins has originally been assumed to
      be mediated by their primary action on membrane lipid matrix. Many studies
      carried out later on both animal and yeast cells have revealed that ethanol and
      other alcohols inhibit the functions of various membrane channels, receptors and
      solute transport proteins, and a direct interaction of alcohols with these
      membrane proteins has been proposed. Using our fluorescence diS-C3 (3) diagnostic
      assay for multidrug-resistance pump inhibitors in a set of isogenic yeast Pdr5p
      and Snq2p mutants, we found that n-alcohols (from ethanol to hexanol) variously
      affect the activity of both pumps. Beginning with propanol, these alcohols have
      an inhibitory effect that increases with increasing length of the alcohol acyl
      chain. While ethanol does not exert any inhibitory effect at any of the
      concentration used (up to 3%), hexanol exerts a strong inhibition at 0.1%. The
      alcohol-induced inhibition of MDR pumps was detected even in cells whose membrane
      functional and structural integrity were not compromised. This supports a notion
      that the inhibitory action does not necessarily involve only changes in the lipid
      matrix of the membrane but may entail a direct interaction of the alcohols with
      the pump proteins. 

PMID- 24028577
TI  - Plasmodium falciparum Hsp70-x: a heat shock protein at the host-parasite
      interface.
AB  - Plasmodium falciparum 70 kDa heat shock proteins (PfHsp70s) are expressed at all
      stages of the pathogenic erythrocytic phase of the malaria parasite life cycle.
      There are six PfHsp70s, all of which have orthologues in other plasmodial
      species, except for PfHsp70-x which is unique to P. falciparum. This research
      highlights a number of original results obtained by a detailed bioinformatics
      analysis of the protein. Large-scale sequence analysis indicated the presence of
      an extended transit peptide sequence of PfHsp70-x which potentially directs it to
      the endoplasmic reticulum (ER). Further analysis showed that PfHsp70-x does not
      have an ER-retention sequence, suggesting that the protein transits through the
      ER and is secreted into the parasitophorous vacuole or beyond into the
      erythrocyte cytosol. These results are consistent with experimental findings.
      Next, possible interactions between PfHsp70-x and exported P. falciparum Hsp40s
      or host erythrocyte Hsp40 were interrogated by modelling and docking. Docking
      results indicated that interaction between PfHsp70-x and each of the Hsp40s,
      regardless of biological feasibility, seems equally likely. This suggests that J
      domain might not provide the specificity in the formation of unique Hsp70-Hsp40
      complexes, but that the specificity might be provided by other domains of Hsp40s.
      By studying different structural conformations of PfHsp70-x, it was shown that
      Hsp40s can only bind when PfHsp70-x is in a certain conformation. Additionally,
      this work highlighted the possible dependence of the substrate-binding domain
      residues on the orientation of the alpha-helical lid for formation of the
      substrate-binding pocket. 

PMID- 24028578
TI  - Rotational spectra of bicyclic decanes: the trans conformation of (-)-lupinine.
AB  - The conformational and structural properties of the bicyclic quinolizidine
      alkaloid (-)-lupinine have been investigated in a supersonic jet expansion using
      microwave spectroscopy. The rotational spectrum is consistent with a single
      dominant trans conformation within a double-chair skeleton, which is stabilized
      by more than 10.4 kJ mol(-1) with respect to other conformations. In the isolated
      conditions of the jet, the hydroxy methyl side chain of the molecule locks in to
      form an intramolecular O-H...N hydrogen bond to the electron lone pair at the
      nitrogen atom. Accurate rotational constants, centrifugal distortion corrections,
      and (14)N nuclear quadrupole coupling parameters are reported and compared to ab
      initio (MP2) and DFT (M06-2X) calculations. The stability of lupinine is further
      compared computationally with epilupinine and decaline in order to gauge the
      influence of intramolecular hydrogen bonding, absent in these molecules. 

PMID- 24028579
TI  - A comparison of the Well Child Clinic services in Norway and the Nurse Family
      Partnership programme in the United States.
AB  - AIM AND OBJECTIVES: To present a comparison and a discussion of the Well Child
      Clinic model in Norway and the Nurse-Family Partnership model in the United
      States. BACKGROUND: The Nurse Family Partnership programme in the United States
      is voluntary and not universal. The Well Child Clinic programme in Norway is
      voluntary but universally available for Norwegian families. As the Well Child
      Clinics are used by the vast majority of the families in Norway, it is difficult
      to determine the benefits and outcomes for the families who receive universal
      services. DESIGN: Qualitative design. METHODS: Authors reviewed the literature on
      the Norwegian Well Child Clinics and the Nurse Family Partnership programme in
      the United States and interviewed public health nurses experts on evidence-based
      home visiting programmes in Minnesota. RESULTS: The similarities between goals
      and content of the Nurse Family Partnership programme in the United States and
      the Well Child Clinic services in Norway are emphases on (1) intensive services,
      (2) a focus on behaviour, (3) the inclusion of both parents and children and (4)
      programme fidelity. The major difference in the programmes is the focus on a
      targeted population for the Nurse Family Partnership programme vs. the universal
      offer of Well Child Clinics in Norway. CONCLUSION: Norway should continue with
      universal approach to support new families. A model similar to Nurse Family
      Partnership could be developed in Norway as an addition to the existing universal
      services, as an offer to the high-risk families. RELEVANCE TO CLINICAL PRACTICE:
      Public health nursing leaders in Norway need to advocate for public health nurse
      ratios that make it possible for public health nurses to follow government
      guidelines. A model similar to Nurse Family Partnership could be developed in
      Norway as an addition to the existing universal services, as an offer to the high
      risk families.

PMID- 24028580
TI  - Interpersonal differentiation within depression diagnosis: relating interpersonal
      subgroups to symptom load and the quality of the early therapeutic alliance.
AB  - We examined interpersonal problems in psychotherapy outpatients with a principal
      diagnosis of a depressive disorder in routine care (n=361). These patients were
      compared to a normative non-clinical sample and to outpatients with other
      principal diagnoses (n=959). Furthermore, these patients were statistically
      assigned to interpersonally defined subgroups that were compared regarding
      symptoms and the quality of the early alliance. The sample of depressive patients
      reported higher levels of interpersonal problems than the normative sample and
      the sample of outpatients without a principal diagnosis of depression. Latent
      Class Analysis identified eight distinct interpersonal subgroups, which differed
      regarding self-reported symptom load and the quality of the early alliance.
      However, therapists' alliance ratings did not differentiate between the groups.
      This interpersonal differentiation within the group of patients with a principal
      diagnosis of depression may add to a personalized psychotherapy based on
      interpersonal profiles.

PMID- 24028581
TI  - Nullifying tumor efflux by prolonged endolysosome vesicles: development of low
      dose anticancer-carbon nanotube drug.
AB  - As the majority of side effects of current chemotherapies stems from toxicity due
      to excessive dosing of anticancer drugs, minimizing the amount of drug while
      maximizing drug efficacy is essential to increase the life-quality of
      chemotherapy patients. This study demonstrated that the intracellular delivery of
      amide linked doxorubicin on carbon nanotube can nullify the efflux of cancer
      cells by achieving prolonged endolysosome delivery and can induce burst release
      of doxorubicin in an acidic hydrolase environment and, ultimately, can reduce the
      amount of anticancer drug by 10-fold compared to conventional effective drug
      dose. The clearance of accumulated carbon nanotubes in the liver was observed
      after 4 weeks, and analysis of liver toxicity markers showed no significant
      changes in GOT and GPT levels and release of pro-inflammatory cytokines across
      both short- and long-term periods. 

PMID- 24028582
TI  - Large-scale pattern of genetic differentiation within African rainforest trees:
      insights on the roles of ecological gradients and past climate changes on the
      evolution of Erythrophleum spp (Fabaceae).
AB  - BACKGROUND: The evolutionary events that have shaped biodiversity patterns in the
      African rainforests are still poorly documented. Past forest fragmentation and
      ecological gradients have been advocated as important drivers of genetic
      differentiation but their respective roles remain unclear. Using nuclear
      microsatellites (nSSRs) and chloroplast non-coding sequences (pDNA), we
      characterised the spatial genetic structure of Erythrophleum (Fabaceae) forest
      trees in West and Central Africa (Guinea Region, GR). This widespread genus
      displays a wide ecological amplitude and taxonomists recognize two forest tree
      species, E. ivorense and E. suaveolens, which are difficult to distinguish in the
      field and often confused. RESULTS: Bayesian-clustering applied on nSSRs of a
      blind sample of 648 specimens identified three major gene pools showing no or
      very limited introgression. They present parapatric distributions correlated to
      rainfall gradients and forest types. One gene pool is restricted to coastal
      evergreen forests and corresponds to E. ivorense; a second one is found in
      gallery forests from the dry forest zone of West Africa and North-West Cameroon
      and corresponds to West-African E. suaveolens; the third gene pool occurs in semi
      evergreen forests and corresponds to Central African E. suaveolens. These gene
      pools have mostly unique pDNA haplotypes but they do not form reciprocally
      monophyletic clades. Nevertheless, pDNA molecular dating indicates that the
      divergence between E. ivorense and Central African E. suaveolens predates the
      Pleistocene. Further Bayesian-clustering applied within each major gene pool
      identified diffuse genetic discontinuities (minor gene pools displaying
      substantial introgression) at a latitude between 0 and 2 degrees N in Central
      Africa for both species, and at a longitude between 5 degrees  and 8 degrees E
      for E. ivorense. Moreover, we detected evidence of past population declines which
      are consistent with historical habitat fragmentation induced by Pleistocene
      climate changes. CONCLUSIONS: Overall, deep genetic differentiation (major gene
      pools) follows ecological gradients that may be at the origin of speciation,
      while diffuse differentiation (minor gene pools) are tentatively interpreted as
      the signature of past forest fragmentation induced by past climate changes.

PMID- 24028583
TI  - Multiple deletions in the polyketide synthase gene repertoire of Mycobacterium
      tuberculosis reveal functional overlap of cell envelope lipids in host-pathogen
      interactions.
AB  - Several specific lipids of the cell envelope are implicated in the pathogenesis
      of M. tuberculosis (Mtb), including phthiocerol dimycocerosates (DIM) that have
      clearly been identified as virulence factors. Others, such as trehalose-derived
      lipids, sulfolipids (SL), diacyltrehaloses (DAT) and polyacyltrehaloses (PAT),
      are believed to be essential for Mtb virulence, but the details of their role
      remain unclear. We therefore investigated the respective contribution of DIM,
      DAT/PAT and SL to tuberculosis by studying a collection of mutants, each with
      impaired production of one or several lipids. We confirmed that among those with
      a single lipid deficiency, only strains lacking DIM were affected in their
      replication in lungs and spleen of mice in comparison to the WT Mtb strain. We
      found also that the additional loss of DAT/PAT, and to a lesser extent of SL,
      increased the attenuated phenotype of the DIM-less mutant. Importantly, the loss
      of DAT/PAT and SL in a DIM-less background also affected Mtb growth in human
      monocyte-derived macrophages (hMDMs). Fluorescence microscopy revealed that
      mutants lacking DIM or DAT/PAT were localized in an acid compartment and that
      bafilomycin A1, an inhibitor of phagosome acidification, rescued the growth
      defect of these mutants. These findings provide evidence for DIM being dominant
      virulence factors that mask the functions of lipids of other families, notably
      DAT/PAT and to a lesser extent of SL, which we showed for the first time to
      contribute to Mtb virulence.

PMID- 24028584
TI  - Recovery of atrioventricular conduction after pacemaker placement following
      cardiac valvular surgery.
AB  - BACKGROUND: Atrioventricular block (AVB) occurs commonly after valve surgery, and
      permanent pacemaker (PPM) implantation is often required. However, the rate and
      time course of spontaneous recovery of AV conduction in these patients is not
      known. The goal of this study was to define the rate and risk factors for late
      high-grade AVB in patients who have PPM implantation for this indication.
      METHODS: Serial PPM or defibrillator interrogation data as well as demographic
      and operative data were reviewed from consecutive patients who had device
      implantation for AVB following valve surgery. Predictors of late AVB were
      identified with multiple regression models, and recovery of AV conduction was
      determined with Kaplan-Meier analyses. RESULTS: Among 98 patients included in the
      analysis, 58% (57/98) had evidence of late high-grade AVB, with a mean follow-up
      of 3.6 years. Of the 57 patients with late AVB after PPM implantation, 44 (77%)
      displayed pacing dependency. In multivariate analyses, persistent AVB in the
      immediate postoperative period was the only variable associated with late AVB
      (odds ratio 5.3, 95% confidence interval [2.1, 13.5], P = 0.0006). Among patients
      who recovered AV conduction within 1 month of surgery, 26% developed AVB during
      extended follow-up. CONCLUSIONS: Approximately 40% of patients who received a PPM
      for AVB after valve surgery displayed no evidence of high-grade AVB during serial
      device interrogations. However, simple baseline demographic, operative, and
      postoperative variables are not sufficiently robust for discriminating those
      patients with early postoperative AVB who will not need long-term pacing
      following valve surgery.

PMID- 24028585
TI  - Comparison of Saliva-Check Mutans and Saliva-Check IgA Mutans with the Cariogram
      for caries risk assessment.
AB  - The purpose of the study was to evaluate the combined use of two rapid,
      semiquantitative detection kits (Saliva-Check Mutans and Saliva-Check IgA Mutans)
      to assess caries risk using the Cariogram computer-based program as a reference
      method. Stimulated saliva samples were collected from 71 subjects, 20-73 yr of
      age, and the number of Streptococcus mutans per ml of saliva was measured using
      Saliva-Check Mutans. After 15 min, a red line in the test detection window
      indicated >5 * 10(5) colony-forming units (CFU) of S. mutans per ml of saliva.
      The concentration of salivary IgA in relation to the number of mutans
      streptococci was examined using the Saliva-Check IgA Mutans test kit. The
      presence or absence of a red line after 15 min indicated a high or a low
      concentration of IgA, respectively. By combining the results obtained from these
      two test systems, each patient was classified into one of four groups of low to
      high caries risk. Compared with the Cariogram data, the combined results of both
      detection kits showed that 39 (95%) of 41 subjects had a high chance of avoiding
      caries and 20 (67%) of 30 subjects had a low chance. The data suggest that the
      combination of Saliva-Check Mutans and Saliva-Check IgA Mutans could be used for
      caries risk assessment.

PMID- 24028586
TI  - Bacterial markers vs. clinical markers to predict progression of chronic
      periodontitis: a 2-yr prospective observational study.
AB  - The aim of this study was to identify sites at risk for future progression,
      during 2 yr of maintenance, in patients with chronic periodontitis (CP), based on
      longitudinal clinical and microbiological monitoring. At baseline (2003),
      clinical and microbiological features were recorded in 50 patients with CP. Two
      microbial samples were obtained from each patient (one from a clinically healthy
      site and one from a periodontitis site) and these were analyzed using DNA-DNA
      hybridization involving 25 bacterial species. After non-surgical periodontal
      therapy, clinical and microbiological re-examinations were performed at the same
      or similar sites at 2 yr (2006) and 4 yr (2008) of maintenance. Plaque, bleeding
      on probing (BoP), and the number of sites with periodontitis (>=4 mm) and severe
      periodontitis (>=6 mm) all showed a significant decrease at 2 and 4 yr of
      maintenance after non-surgical intervention. Checkerboard analysis revealed that
      various bacteria with a high colonization score (>=3) corroborated the clinical
      findings of pathology at 2003, 2006, and 2008. Different clusters of bacteria,
      not just the 'red complex', were able to predict progression of chronic
      periodontitis during 2 yr of maintenance (2006-2008). Therefore, quantified
      bacterial markers (reflecting bacterial load) and the clinical markers BoP and
      periodontal probing depth show comparable prediction of future disease condition.

PMID- 24028587
TI  - Novel PAX9 mutation associated with syndromic tooth agenesis.
AB  - Tooth agenesis is the most common anomaly of dental development. The purpose of
      the present study was to identify the causative mutation(s) in a family with a
      syndromic form of hypodontia. The male proband lacked 19 permanent teeth and
      showed defects of hair, but lacked ectodermal symptoms of skin and nails. Direct
      sequencing of the coding regions, including exon/intron boundaries of the msh
      homeobox 1 (MSX1), paired box 9 (PAX9), ectodysplasin A (EDA), and wingless-type
      MMTV integration site family, member 10 (WNT10A) genes, was carried out in
      affected family members. All identified nucleotide variations were tested in 200
      healthy individuals using high-resolution melting (HRM) curve analysis to exclude
      the possibility that they represent rare polymorphisms. A novel heterozygous
      c.59delC mutation, segregating in the autosomal-dominant model, was identified in
      the PAX9 gene of the proband and the family members studied. This one-nucleotide
      deletion, located in a highly conserved paired box sequence, resulted in a
      frameshift (p.Pro20Argfs65) and in premature termination of translation, yielding
      a truncated protein 258 amino acids shorter than the wildtype protein. No
      pathogenic mutations were found in the MSX1, EDA, and WNT10A genes. In
      conclusion, the novel PAX9 deletion might be responsible for tooth agenesis and
      trichodysplasia in the investigated family. This c.59delC mutation potentially
      leads to PAX9 transcription factor haploinsufficiency. 

PMID- 24028588
TI  - Msx1 regulates proliferation and differentiation of mouse dental mesenchymal
      cells in culture.
AB  - The homeobox, msh-like 1 (MSX1) protein is essential for cell proliferation and
      differentiation. Tooth germ development of Msx1 knockout mouse is arrested at the
      bud stage, impeding an understanding of its role beyond this stage of tooth
      development. The aims of this study were to investigate the potential role of
      MSX1 in the regulation of proliferation and differentiation of dental mesenchymal
      cells in culture, and to preliminarily explore its underlying mechanism of
      action. Tooth germs were isolated from embryonic day (E)15.5 mice. The mesenchyme
      was separated and digested into a single-cell suspension, and then cultured in
      vitro. Isolated dental mesenchymal cells were transfected with MSX1 small
      interfering RNA, and the effects on cell proliferation, cell cycle distribution,
      and the expression of bone morphogenetic protein 2 (Bmp2) and bone morphogenetic
      protein 4 (Bmp4) were studied. We also compared the expression levels of alkaline
      phosphatase (Alp), type I collagen (Col1A), osteocalcin (Ocn), runt-related
      transcription factor 2 (Runx2), dentin sialophosphoprotein (Dspp) and dentin
      matrix protein 1 (Dmp1), and mineralized nodule formation, between control and
      MSX1 siRNA-transfected groups after the induction of odontoblast differentiation.
      Knockdown of Msx1 expression was associated with decreased cell proliferation,
      prolonged time in the S phase of the cell cycle, enhanced odontoblast
      differentiation, and elevated Bmp2 and Bmp4 expression. We conclude that MSX1 may
      promote proliferation and prevent the differentiation of dental mesenchymal cells
      by the inhibition of Bmp2 and Bmp4 expression. 

PMID- 24028589
TI  - TLR2, TLR3, TLR4 and CD14 gene polymorphisms associated with oral lichen planus
      risk.
AB  - The aim of this study was to assess whether polymorphisms in toll-like receptor
      (TLR) and cluster of differentiation 14 (CD14) genes are associated with oral
      lichen planus (OLP) risk and clinical course of the disease. The study group
      consisted of 101 patients with confirmed OLP and 104 healthy blood donors without
      systemic or oral mucosal diseases. Single nucleotide polymorphisms of TLR2
      (rs3804099), TLR3 (rs3775291 and rs5743312), TLR4 (rs4986790 and rs4986791), and
      CD14 (rs2569190) genes were genotyped using real-time PCR or PCR-restriction
      fragment length polymorphism (PCR-RFLP). The rs5743312 TLR3 gene polymorphism was
      associated with increased OLP risk in comparison with the wild type genotype (OR
      = 15.984, P = 0.011). No association with OLP risk was observed for the
      polymorphisms studied in TLR2, TLR4 and CD14 genes or for the rs3775291
      polymorphism of the TLR3 gene. The polymorphisms of the TLR3 gene were in linkage
      disequilibrium (D' = 1, r(2) = 0.1). Identified haplotypes were not associated
      with the risk of OLP. The findings of the current study suggest that the TT
      genotype of the rs5743312 TLR3 gene polymorphism may play a significant role in
      the aetiology of OLP.

PMID- 24028590
TI  - Unstimulated whole salivary flow rate and anxiolytics intake are independently
      associated with oral Candida infection in patients with oral lichen planus.
AB  - Many factors have been proposed to influence oral infection with yeast. The aim
      of this study was to determine the prevalence of oral yeasts in oral lichen
      planus (OLP) patients and control subjects, and to perform a multiple logistic
      regression analysis to identify factors that influence oral Candida infection in
      OLP patients. In this cross-sectional study, 90 new patients with OLP and 90 sex-
      and age-matched control subjects with no mucosal lesions were interviewed about
      their health status, use of medication, and smoking and alcohol habits. Swab and
      unstimulated whole saliva samples were collected and salivary pH was measured. A
      positive Candida culture was more prevalent among OLP patients (48.9%) than among
      control subjects (26.7%). Candida albicans was the most frequently isolated
      species in both groups. By logistic regression analysis, unstimulated whole
      salivary flow rates of 0.11-0.24 ml min(-1) (OR = 5.90) and 0.25-0.32 ml min(-1)
      (OR = 3.51) and benzodiazepine anxiolytics intake (OR = 8.30) were independently
      associated with the presence of Candida among OLP patients. Age, denture wearing,
      levels of dentition, decreased salivary pH, antihypertensive drugs, and alcohol
      consumption were not associated with oral Candida infection in OLP patients. The
      results indicate that data on benzodiazepine anxiolytics intake and evaluation of
      unstimulated whole salivary flow rate should be considered as part of the
      clinical evaluation to identify OLP patients at risk for Candida infection.

PMID- 24028591
TI  - Neutral endopeptidase regulates neurogenic inflammatory responses induced by
      stimulation of human oral keratinocytes with bacterial lipopolysaccharide and
      nicotine.
AB  - Neutral endopeptidase (NEP) is present on various epithelial cells and
      inactivates numerous physiologically active peptides. Neutral endopeptidase may
      regulate proinflammatory signals in oral mucosal epithelium. However, the
      function of NEP in oral mucosal epithelium is unknown. The present study
      investigated the action of NEP upon proinflammatory signals on human oral
      keratinocytes and the influence of endothelin-converting enzyme (ECE)-1, an
      enzyme similar to NEP, on the functions of NEP. Oral keratinocytes were cultured
      in medium containing inflammatory inducers [lipopolysaccharide (LPS) and
      nicotine], NEP inhibitors, and ECE-1/NEP inhibitors, either alone or in
      combination. The concentrations of substance P (SP) and interleukin-1beta (IL
      1beta) were measured in the supernatant. Additionally, the concentrations of SP
      and IL-1beta were measured in the supernatant of cells incubated with LPS or
      nicotine after transfection with NEP small interfering RNA (siRNA). The
      concentrations of SP and IL-1beta were significantly increased in cells incubated
      with NEP inhibitors and, to a lesser extent, in cells incubated with ECE-1/NEP
      inhibitors, compared with controls (cells incubated with LPS or nicotine alone).
      The concentrations of SP and IL-1beta in cells transfected with NEP siRNA were
      significantly augmented compared with controls. In conclusion, the present study
      demonstrated that NEP down-regulated the levels of SP and IL-1beta produced from
      human oral keratinocytes, although ECE-1 may be partly related to the down
      regulation. 

PMID- 24028592
TI  - Increased sternocleidomastoid, but not trapezius, muscle activity in response to
      increased chewing load.
AB  - Previous findings, during chewing, that boluses of larger size and harder texture
      result in larger amplitudes of both mandibular and head-neck movements suggest a
      relationship between increased chewing load and incremental recruitment of jaw
      and neck muscles. The present report evaluated jaw (masseter and digastric) and
      neck [sternocleidomastoid (SCM) and trapezius] muscle activity during the chewing
      of test foods of different sizes and textures by 10 healthy subjects. Muscle
      activity was recorded by surface electromyography and simultaneous mandibular and
      head movements were recorded using an optoelectronic technique. Each subject
      performed continuous jaw-opening/jaw-closing movements whilst chewing small and
      large boluses of chewing gum and rubber silicone (Optosil). For jaw opening/jaw
      closing without a bolus, SCM activity was recorded for jaw opening concomitantly
      with digastric activity. During chewing, SCM activity was recorded for jaw
      closing concomitantly with masseter activity. Trapezius activity was present in
      some, but not all, cycles. For the masseter and SCM muscles, higher activity was
      seen with larger test foods, suggesting increased demand and recruitment of these
      muscles in response to an increased chewing load. This result reinforces the
      previous notion of a close functional connection between the jaw and the neck
      motor systems in jaw actions and has scientific and clinical significance for
      studying jaw function and dysfunction. 

PMID- 24028593
TI  - Volumetric changes of the nose and nasal airway 2 years after tooth-borne and
      bone-borne surgically assisted rapid maxillary expansion.
AB  - This study aimed to assess the effects of bone-borne and tooth-borne surgically
      assisted rapid maxillary expansion on the volumes of the nose and nasal airway 2
      yr after maxillary expansion. This prospective cohort study included 32 patients
      with transverse maxillary hypoplasia. Expansion was performed with a tooth-borne
      distractor (Hyrax) in 19 patients and with a bone-borne distractor [transpalatal
      distractor (TPD)] in the remaining 13. Cone beam computed tomography scans and
      three-dimensional (3D) photographs of the face were acquired before treatment and
      22 +/- 7 months later, and were used to evaluate the volumes of the nose and
      nasal airway. Nasal volume increased by 1.01 +/- 1.6% in the Hyrax group and by
      2.39 +/- 2.4% in the TPD group. Nasal airway volume increased by 9.7 +/- 5.6% in
      the Hyrax group and by 12.9 +/- 12.7% in the TPD group. Changes in the nasal
      volume and in the nasal airway volume between the pre- and post-treatment
      measurements were statistically significant, whereas differences between the
      treatment groups were not; 22 months after surgically assisted rapid maxillary
      expansion, the increases in the nasal volume and in the nasal airway volume were
      comparable between tooth-borne and bone-borne devices.

PMID- 24028594
TI  - Total fluoride intake and excretion in children up to 4 years of age living in
      fluoridated and non-fluoridated areas.
AB  - Fractional fluoride retention is important during the early years of life when
      considering the risk of development of dental fluorosis. This study aimed to
      measure fractional fluoride retention in young children. The objectives were to
      investigate the relationships between fractional fluoride retention and total
      daily fluoride intake, age, and body mass index (BMI). Twenty-nine healthy
      children, up to 4 yr of age, participated; 14 lived in a fluoridated area (0.64
      MUg ml(-1) of fluoride in drinking water) and 15 lived in a non-fluoridated area
      (0.04 MUg ml(-1) of fluoride in drinking water). The total daily fluoride intake
      of each child was calculated from the daily dietary fluoride intake and
      toothpaste ingestion (if fluoride toothpaste was used). Total daily fluoride
      excretion was measured by collecting voided urine and faeces over a 24-h period,
      and fractional fluoride retention was calculated by dividing the amount of
      fluoride retained in the body (total daily fluoride intake minus total daily
      fluoride excretion) by the total daily fluoride intake. Nine children were
      excluded from data analysis because of suspected invalid samples. Mean (range)
      fractional fluoride retention for the remaining 20 children was 0.61 (0.06-0.98).
      There were no statistically significant correlations between fractional fluoride
      retention and either age or BMI. However, fractional fluoride retention was
      correlated with total daily fluoride intake: fractional fluoride retention = 1 -
      exp (-C * total daily fluoride intake), where C = 28.75 (95% CI = 19.75-37.75).
      The wide variation in fluoride retention in young children could have important
      implications when recommendations for fluoride use are being considered.

PMID- 24028595
TI  - Can you read my pokerface? A study on sex differences in dentophobia.
AB  - Men and women with dentophobia differ in specific fear contents and underlying
      brain activity during symptom provocation. Possible sex differences concerning
      other basic emotions, such as disgust, have undergone minimal investigation.
      Therefore, we recorded the facial electromyogram from the musculus levator labii
      (as a specific disgust indicator) and the heart rate of 36 individuals with
      dentophobia (18 women and 18 men with comparable disorder severity) and of 36 non
      phobic controls (18 women and 18 men). The participants were asked to look at
      pictures showing dental treatment scenes, generally fear- and disgust-inducing,
      as well as pictures with neutral contents. Subsequently they performed an
      affective picture rating. Independently of sex, phobic subjects relative to
      controls showed heart-rate acceleration when watching pictures of dental
      treatment scenes, reflecting a fear reaction. Male and female phobic subjects did
      not differ in their verbal reports of fear and disgust experienced. However,
      phobic women showed enhanced disgust-related facial electromyographic activity to
      dental treatment scenes relative to men. This sex-specific response pattern
      points to the greater relevance of disgust for the female symptomatology of
      dentophobia, or it might also be possible that male patients more successfully
      inhibit disgust reactions during confrontation. 

PMID- 24028596
TI  - Awareness and attitudes related to dental erosive wear among 18-yr-old
      adolescents in Oslo, Norway.
AB  - The aim of the present study was to describe awareness and attitudes related to
      dental erosive wear among 18-yr-old adolescents in Oslo and to explore
      attitudinal differences between participants with and without the condition. All
      18-yr-old subjects scheduled for their routine examination at the Public Dental
      Service clinics during 2008 (n = 3,206) were invited, and 1,456 agreed to
      participate (a response rate of 45%). The data were collected using structured
      questionnaires and by clinical examination of the participants. Dental erosive
      wear was assessed using a pictorial manual - the Visual Erosion Dental
      Examination scoring system - as a guide. Overall, 88% of participants had heard
      about dental erosive wear; however, of participants with erosive lesions only 56%
      were aware of, and only 47% could recall their dentist mentioning, the condition.
      Participants with erosive wear were more likely to have low or moderate positive
      attitudes towards acidic drink consumption and to be reluctant to change. In
      multivariate analyses controlling for gender and behavioural variables, weak or
      moderate positive awareness of acidic drinks remained significantly associated
      with higher erosion risk. This study emphasizes the importance of assessment and
      understanding of awareness and attitudinal aspects in relation to dental erosive
      wear.

PMID- 24028597
TI  - Clinical trial of tooth desensitization prior to in-office bleaching.
AB  - The aim of this clinical trial was to compare tooth sensitivity during and after
      bleaching with hydrogen peroxide gel following application of GLUMA Desensitizer
      PowerGel or placebo. Forty-six subjects with sound maxillary incisors and canines
      were enrolled. Tooth shades were determined by comparison with a Vitapan Classic
      Shade guide. GLUMA Desensitizer PowerGel and placebo were randomly applied to the
      labial surfaces of the left or right anterior teeth for 1 min, which were then
      rinsed and dried. Then, Opalescence Boost PF 40% gel was applied onto labial
      enamel for 15 min. Sensitivity scores [recorded on a 10-point visual-analog scale
      (VAS)] were determined before, at 5, 10, and 15 min during, and 1, 24, 48 h and 1
      wk after, the bleaching treatment. Shades were determined postbleaching and after
      1 wk. Prebleaching application of GLUMA Desensitizer PowerGel significantly
      reduced tooth sensitivity during and after bleaching when compared with treatment
      with placebo. The whitening effects immediately and 1 wk after bleaching were
      significant when compared with the prebleaching shades. In conclusion, tooth
      pretreatment with GLUMA Desensitizer PowerGel for 1 min prior to 15 min of in
      office bleaching with 40% hydrogen peroxide gel was highly effective in reducing
      tooth sensitivity during and after bleaching.

PMID- 24028598
TI  - Detection of leachables and cytotoxicity after exposure to methacrylate- and
      epoxy-based root canal sealers in vitro.
AB  - Root canal sealing materials may have toxic potential in vitro depending on the
      cell line, cytotoxicity assay, material chemistry, and degree of polymer curing.
      The aims of the present study were to detect leaching components from epoxy- or
      methacrylate-based root canal sealers and to investigate the degree of
      cytotoxicity after exposure to extracts from these materials. Qualitative
      determination of substances released from the materials was performed by gas- and
      liquid chromatography/mass spectrometry. Submandibular salivary gland acinar cell
      death (apoptosis/necrosis) was determined using a fluorescence
      staining/microscopy technique. The major leachable monomer from the epoxy-based
      material was bisphenol-A diglycidyl ether (BADGE), whereas leachables from the
      methacrylate-based materials were mainly triethylene glycol dimethacrylate
      (TEGDMA), urethane dimethacrylate (UDMA), hydroxyethyl methacrylate (HEMA), and
      polyethyleneglycol dimethacrylate (PEGDMA). Exposure to diluted extracts of cured
      methacrylate-based materials caused a postexposure time-dependent increase in
      cell death. This effect was not demonstrated as a result of exposure to undiluted
      extract of cured epoxy-based material. Extracts of all fresh materials induced
      apoptosis significantly, but at lower dilutions of the epoxy- than the
      methacrylate-based materials. The degree of leaching, determined from the
      relative chromatogram peak heights of eluates from the methacrylate-based sealer
      materials, corresponded with the degree of cell death induced by extracts of
      these materials. 

PMID- 24028599
TI  - Influence of oxygen-inhibited layer on dentin bond strength of chemical-cured
      resin composite.
AB  - This study evaluated the influence of an oxygen-inhibited layer on the surface
      free energies of three single-step self-etch adhesives and on the bond strength
      of chemical-cured resin. Adhesives were applied to bovine dentin and light
      irradiated, and the oxygen-inhibited layer was either retained or removed.
      Surface free energies were determined by measuring the contact angles of test
      liquids placed on the cured adhesives. Dentin bond strengths of chemical-cured
      resin with and without the oxygen-inhibited layer were measured. Ultrastructural
      observation of the restorative-dentin interface was made by scanning electron
      microscopy. For all surfaces, values of the estimated surface tension component,
      Lifshitz-Van der Waals force (gammaS(LW)), were relatively constant. Values for
      the Lewis acid (gammaS(+)) component increased slightly when the oxygen-inhibited
      layer was removed, whereas those of the Lewis base (gammaS(-)) component
      decreased significantly. The bond strength of the chemical-cured resin composite
      was significantly higher in specimens without an oxygen-inhibited layer (7.6-8.0
      MPa) than in those with an oxygen-inhibited layer (4.8-5.2 MPa). Small gaps
      between adhesive and resin composite were found for the group with an oxygen
      inhibited layer. These results indicate that the absence of an oxygen-inhibited
      layer in single-step self-etch adhesives promotes higher dentin bond strength of
      the chemical-cured resin.

PMID- 24028600
TI  - Evaluation of thermal stress in hydroxyapatite film fabricated by powder jet
      deposition.
AB  - This study aimed to create a thick hydroxyapatite (HA) film on the surface of a
      human tooth via a powder jet deposition (PJD) device for dental handpieces, and
      to examine the microstructural and mechanical properties of the HA film. In
      particular, the effects of thermal stress on this film were evaluated. The HA
      film was created by blasting 3.18-MUm HA particles, calcinated at 1,200 degrees
      C, onto the enamel substrate at room temperature and atmospheric pressure. An HA
      film with an area of 3 mm * 3 mm was prepared and polished. The following HA film
      parameters were evaluated from the three-dimensional surface profile: surface
      roughness, Vickers hardness, and bonding strength before and after artificial
      aging induced by 500 cycles of thermal cycling (5-55 degrees C). The HA particles
      in the deposited film were densely packed, and the surface of the HA film was
      unchanged after thermal cycling. There were also no significant differences in
      the hardness and the bonding strength of the HA film before and after thermal
      cycling. The HA film created in this study demonstrated excellent microstructural
      and mechanical properties, even after the application of thermal stress.

PMID- 24028601
TI  - Lung ultrasonography for the diagnosis of neonatal lung disease.
AB  - Ultrasound has recently become an important method for diagnostic examination and
      monitoring of lung disease. Many lung diseases, such as respiratory distress
      syndrome, transient tachypnea of the newborn, pneumonia, atelectasis and
      pneumothorax were diagnosed by chest X-ray or CT scan in the past, but can now
      easily be diagnosed with lung ultrasound. Lung ultrasound has many advantages
      over X-ray and CT scan including accuracy, reliability, low-cost and simplicity,
      as well as the fact that ultrasound incurs no risk of radiation damage. It is
      therefore feasible and convenient to perform at the bedside in a neonatal ward.
      This review focuses on features of bedside lung ultrasound and diagnosis features
      of common lung diseases in newborn infants, culminating in suggestions for
      improving the application of ultrasound in the neonatal field.

PMID- 24028602
TI  - Parthenolide and costunolide reduce microtentacles and tumor cell attachment by
      selectively targeting detyrosinated tubulin independent from NF-kappaB
      inhibition.
AB  - INTRODUCTION: Detyrosinated tubulin, a post-translational modification of alpha
      tubulin and a hallmark of stable microtubules, has gained recent attention given
      its association with tumor progression, invasiveness, and chemoresistance. We
      also recently reported that epithelial-to-mesenchymal transition (EMT) promotes
      tubulin detyrosination through tubulin tyrosine ligase (TTL) suppression.
      Furthermore, detyrosinated tubulin-enriched membrane protrusions, termed
      microtentacles (McTN), facilitate tumor cell reattachment to endothelial layers.
      Given the induction of EMT associated with inflammation and cancer progression,
      we tested anti-inflammatory nuclear factor-kappaB (NF-kappaB) inhibitors on a
      panel of human breast carcinoma cells to examine their effects on detyrosinated
      tubulin to identify more specific tubulin-directed anti-cancer treatments.
      METHODS: Using metastatic human breast carcinoma cells MDA-MB-157, MDA-MB-436,
      and Bt-549, we measured the impact of NF-kappaB inhibitors parthenolide,
      costunolide, and resveratrol on detyrosinated tubulin using protein expression
      analysis and immunofluorescence. A luciferase reporter assay and a viability
      screen were performed to determine if the effects were associated with their NF
      kappaB inhibitory properties or were a result of apoptosis. Real-time monitoring
      of cell-substratum attachment was measured utilizing electrical impedance across
      microelectronic sensor arrays. We compared the selectivity of the NF-kappaB
      inhibitors to specifically target detyrosinated tubulin with traditional tubulin
      targeted therapeutics, paclitaxel and colchicine, throughout the study. RESULTS:
      Sesquiterpene lactones, parthenolide and costunolide, selectively decrease
      detyrosinated tubulin independent of their inhibition of NF-kappaB. Live-cell
      scoring of suspended cells treated with parthenolide and costunolide show
      reduction in the frequency of microtentacles and inhibition of reattachment.
      Structural analysis shows that parthenolide and costunolide can decrease
      detyrosinated microtubules without significantly disrupting the overall
      microtubule network or cell viability. Paclitaxel and colchicine display
      indiscriminate disruption of the microtubule network. CONCLUSIONS: Our data
      demonstrate that selective targeting of detyrosinated tubulin with parthenolide
      and costunolide can reduce McTN frequency and inhibit tumor cell reattachment.
      These actions are independent of their effects on NF-kappaB inhibition presenting
      a novel anti-cancer property and therapeutic opportunity to selectively target a
      stable subset of microtubules in circulating tumor cells to reduce metastatic
      potential with less toxicity in breast cancer patients.

PMID- 24028603
TI  - Review of the safety and efficacy of vitamin A supplementation in the treatment
      of children with severe acute malnutrition.
AB  - BACKGROUND: World Health Organization (WHO) guidelines recommend for children
      with severe acute malnutrition (SAM), high-dose vitamin A (VA) supplements be
      given on day 1 of admission, and on days 2 and 14 in the case of clinical signs
      of vitamin A deficiency (VAD). Daily low-dose VA follows, delivered in a premix
      added to F-75 and F-100. This study aimed to systematically review the evidence
      for safety and effectiveness of high-dose VA supplementation (VAS) in treatment
      of children with SAM. METHODS: A comprehensive literature review was undertaken
      for all relevant randomized controlled trials (RCT) and observational studies
      from 1950 to 2012. Studies identified for full review were evaluated using the
      Grading of Recommendations, Assessment, Development and Evaluation (GRADE)
      methodology using a set of pre-defined criteria: indirectness; inconsistency;
      imprecision; and study limitations. A quality rating of high, moderate, or low
      was then assigned to each study, and only those attaining moderate to high were
      considered in making recommendations. RESULTS: Of the 2072 abstracts screened, 38
      met criteria for full review, and 20 were rated moderate to high quality. Only
      one study replicated the WHO VA protocol in children with SAM. Indirectness was a
      critical limitation, as studies were not exclusive to children with SAM. There
      was inconsistency across trials for definitions of malnutrition, morbidities, and
      ages studied; and imprecision arising from sub-group analyses and small sample
      sizes. Evidence showed improved outcomes associated with low-dose compared to
      high-dose VAS, except in cases presenting with signs of VAD, measles, and severe
      diarrhea or shigellosis. Adverse outcomes related to respiratory infection,
      diarrhea, and growth were associated with high-dose VAS in children who were
      predominantly adequately nourished. No adverse effects of the high dose were
      found in children with SAM in the trial that replicated the WHO VA guideline.
      CONCLUSION: This is the first systematic review of the safety and efficacy of
      high-dose VAS in treatment of SAM. We recommend a low-dose VAS regimen for
      children with SAM, except in cases presenting with measles, severe diarrhea
      (shigellosis), and any indication of VAD. Further research is needed in
      exclusively malnourished children and to explore alternate delivery strategies.

PMID- 24028604
TI  - A survey study of the association between mobile phone use and daytime sleepiness
      in California high school students.
AB  - BACKGROUND: Mobile phone use is near ubiquitous in teenagers. Paralleling the
      rise in mobile phone use is an equally rapid decline in the amount of time
      teenagers are spending asleep at night. Prior research indicates that there might
      be a relationship between daytime sleepiness and nocturnal mobile phone use in
      teenagers in a variety of countries. As such, the aim of this study was to see if
      there was an association between mobile phone use, especially at night, and
      sleepiness in a group of U.S. teenagers. METHODS: A questionnaire containing an
      Epworth Sleepiness Scale (ESS) modified for use in teens and questions about
      qualitative and quantitative use of the mobile phone was completed by students
      attending Mountain View High School in Mountain View, California (n = 211).
      RESULTS: Multivariate regression analysis indicated that ESS score was
      significantly associated with being female, feeling a need to be accessible by
      mobile phone all of the time, and a past attempt to reduce mobile phone use. The
      number of daily texts or phone calls was not directly associated with ESS. Those
      individuals who felt they needed to be accessible and those who had attempted to
      reduce mobile phone use were also ones who stayed up later to use the mobile
      phone and were awakened more often at night by the mobile phone. CONCLUSIONS: The
      relationship between daytime sleepiness and mobile phone use was not directly
      related to the volume of texting but may be related to the temporal pattern of
      mobile phone use.

PMID- 24028605
TI  - Effect of glycemic control on microalbuminuria development among type 2 diabetes
      with high-normal albuminuria.
AB  - This study was aimed at revealing the factors and the interrelationships between
      factors on microalbuminuria development among type 2 diabetes (T2D) patients.
      Between 2004 and 2011, 461 T2D patients with a baseline urine albumin-to
      creatinine ratio (UACR) of <30 mg/g, and an estimated glomerular filtration rate
      (eGFR) of >60 mL/min were evaluated retrospectively. Sixty-eight (14.8%) subjects
      had developed microalbuminuria in a mean follow-up of 6.82 years. Statistical
      analysis had revealed that the higher baseline UACR (10 mg/g; sensitivity, 80.9%,
      specificity, 63.6%; AUC = 0.774) and glycohemoglobin level (HbA1c) (8%;
      sensitivity, 72.1%, specificity, 61.6%; AUC = 0.698) were the two independent
      microalbuminuria risk factors. When considering the risk of microalbuminuria, the
      data were normalized with respect to subjects with low-normal UACR (<10 mg/g) and
      HbA1c < 8%. The adjusted hazard ratio for subjects with low-normal UACR/HbA1c >
      8%, high-normal UACR/HbA1c < 8%, and high-normal UACR/HbA1c >8% were 2.59 (p =
      0.107), 6.15 (p = 0.001), and 16.96 (p < 0.001), respectively. It was determined
      that an increase of HbA1c levels (<8, 8-9, 9-10, >10%) showed a progressively
      increase of the hazard risk in baseline high-normal UACR group. But the same
      correlation was not shown in the low-normal UACR group. This study identified the
      relationships of high-normal albuminuria and glycemic control on microalbuminuria
      development among T2D patients. Glycemic control is especially beneficial for T2D
      patients with baseline high-normal UACR in preventing microalbuminuria
      development.

PMID- 24028606
TI  - Gastrointestinal tone; its genesis and contribution to the physical processes of
      digestion.
AB  - BACKGROUND: Myogenic tone has long been recognised as an important component of
      gastrointestinal motility. Recent work has clarified the cellular mechanisms that
      engender tone and the neurogenic and mechanical stimuli that modulate it but has
      also highlighted cellular and regional specialisation in these mechanisms within
      the GI tract. Smooth muscle in all segments of the gut has the capability of
      latching, i.e. can generate ongoing specific rather than tetanic tone. This is
      likely modulated by both direct and indirect input from agonists such as
      acetylcholine and mechanoreceptors, the latter originating in ICC-IM, smooth
      muscle cells or elements of the ENS. Tonic contraction can occur in the absence
      of phasic contractions or concurrent with them, and it can modulate wall
      compliance and the capacity of particular segments, thereby affecting the level
      of on-flow and mixing, both luminal and adjacent to the mucosa. PURPOSE: The
      review seeks to provide an overview of our understanding of the mechanism by
      which tone is generated and maintained, highlighting its modulation by neurogenic
      and mechanical stimuli, its mechanical consequences in the walls of the various
      segments of the gastrointestinal tract and its contribution to flow and mixing of
      contained digesta.

PMID- 24028607
TI  - Metabolite profiling driven analysis of Salsola species and their anti
      acetylcholinesterase potential.
AB  - Over 100 species of the genus Salsola are distributed in dry, arid parts of Asia,
      Europe and Africa, of which many species are recognised as antifungal,
      anticancer, antihypertensive and anthelmintic agents. Egyptian Salsola received
      scant characterisation of either its phytochemical composition or its biological
      effects. In this study, the metabolite profiles of two Salsola species viz. S.
      vermiculata and S. tetrandra were characterised in the aerial portions and root
      via ultra-performance liquid chromatography high-resolution qTOF-MS and NMR.
      Identified metabolites belonged to various classes including hydroxycinnamic acid
      conjugates, flavonoids, oxygenated fatty acids and alkaloids. Principal component
      analysis of derived biochemical profiles was also used for species and/or organs
      classification. Roots were enriched in hydroxycinnamic acid conjugates, whereas
      flavonoids were more abundant in aerial parts with kaempferol derivatives as
      major flavonoids in S. tetrandra versus quercetin in S. vermiculata. The root of
      S. vermiculata exhibited strong anti-acetylcholinesterase activity relative to
      eserine standard. 

PMID- 24028608
TI  - A prospective evaluation of the utility of the prehospital 12-lead
      electrocardiogram to change patient management in the emergency department.
AB  - OBJECTIVE: Retrospective research has shown that 19% of 12-lead prehospital
      electrocardiograms (prehospital ECGs) had clinically significant abnormalities
      that were not captured on the initial emergency department (ED) ECG and had the
      potential to change medical management. The purpose of this study was to
      prospectively determine how many prehospital ECGs had clinically significant
      abnormalities not present on the initial ED ECG and determine how many
      prehospital ECGs changed physician management. METHODS: We conducted a 3-month,
      prospective cohort study of patients who had a 12-lead prehospital ECG completed
      by EMS prior to arriving at one of two tertiary care EDs. STEMI bypass patients
      were excluded. Physicians reviewed the prehospital ECG to determine whether there
      were any clinically significant abnormalities present on the prehospital ECG not
      captured on the initial ED ECG. Physicians recorded if and how the prehospital
      ECG changed their management. RESULTS: A total of 281 patients were enrolled.
      Thirty-five (12.5%; 95% CI: 9.1%, 16.8%) prehospital ECGs showed changes that
      were not captured on the initial ED ECG (11 ST depression, 5 T-wave inversion
      [TWI], 2 ST depression and TWI, 12 arrhythmia, 2 arrhythmia with ST depression, 2
      ST elevation, 1 unknown). Fifty-two (18.5%; 95% CI: 14.4%, 23.5%) prehospital
      ECGs influenced physician management. There were 30 (10.7%) instances where
      physicians were willing to refer the patient to an inpatient service based on
      information captured on the prehospital ECG, regardless if the initial ED ECG was
      normal. CONCLUSIONS: Prehospital ECGs show clinically significant abnormalities
      that are not always captured on the initial ED ECG. Prehospital ECGs have the
      potential to change the management of patients in the ED.

PMID- 24028609
TI  - Surface passivation of efficient nanotextured black silicon solar cells using
      thermal atomic layer deposition.
AB  - Efficient nanotextured black silicon solar cells passivated by an Al2O3 layer are
      demonstrated. The broadband antireflection of the nanotextured black silicon
      solar cells was provided by fabricating vertically aligned silicon nanowire
      (SiNW) arrays on the n(+) emitter. A highly conformal Al2O3 layer was deposited
      upon the SiNW arrays by the thermal atomic layer deposition (ALD) based on the
      multiple pulses scheme. The nanotextured black silicon wafer covered with the
      Al2O3 layer exhibited a low total reflectance of ~1.5% in a broad spectrum from
      400 to 800 nm. The Al2O3 passivation layer also contributes to the suppressed
      surface recombination, which was explored in terms of the chemical and field
      effect passivation effects. An 8% increment of short-circuit current density and
      10.3% enhancement of efficiency were achieved due to the ALD Al2O3 surface
      passivation and forming gas annealing. A high efficiency up to 18.2% was realized
      in the ALD Al2O3-passivated nanotextured black silicon solar cells. 

PMID- 24028610
TI  - In-vitro prediction of bioavailability following extravascular injection of
      poorly soluble drugs: an insight into clinical failure and the role of delivery
      systems.
AB  - OBJECTIVES: To investigate the feasibility of using an in-vitro model to simulate
      the incidence of post-injection drug precipitation (PDP), and to identify the
      roles of drug properties and delivery systems in its occurrence. METHODS: A
      literature review on incomplete absorption following extravascular injection
      (subcutaneous and intramuscular) was conducted. Six model drugs in nine different
      formulations were studied for an in-vitro/in-vivo correlation. A rapid in-vitro
      dilution method using a 96-well plate was used for predicting PDP by dilution
      with a physiological buffer. New formulations based on hydroxypropyl-beta
      cyclodextrin (CD), with and without co-solvents or pH control, were developed and
      tested on the in-vitro model. KEY FINDINGS: The occurrence of precipitation
      detected from the in-vitro dilution model appeared to be correlated with clinical
      reports and animal studies. The formulation components played an important role
      in determining the potential for drug precipitation on dilution or pH
      neutralization. CD was found to reduce the tendency for precipitation. The
      addition of co-solvents may reduce the effect of CD, depending on the solvent
      used. CONCLUSIONS: The in-vitro model can be used as a cost-effective screening
      tool in injectable formulation development for safe and effective delivery of
      poorly soluble drugs. PDP can be circumvented with a well-designed formulation.

PMID- 24028611
TI  - Optimization of self-microemulsifying drug delivery system for telmisartan using
      Box-Behnken design and desirability function.
AB  - OBJECTIVES: To develop and optimize the novel self-microemulsifying drug delivery
      system (SMEDDS) formulation for enhanced water solubility and bioavailability of
      telmisartan (TMS) using the Box-Behnken design (BBD) and desirability function.
      METHOD: TMS-SMEDDS formulation consisted of the mixture of oil (Peceol),
      surfactant (Labrasol), co-surfactant (Transcutol), TMS and triethanolamine. A
      three-level BBD was applied to explore the main effect, interaction effect and
      quadratic effect of three independent variables, including the amount of Peceol
      (X1 ), Labrasol (X2 ) and Transcutol (X3 ). Determined conditions were 20 < X1  <
      40, 50 < X2  < 80 and 5 < X3  < 30. The response variables were droplet size (Y1
      ), polydispersity index (Y2 ) and dissolution percentage of TMS after 15 min (Y3
      ). KEY FINDINGS: The optimized conditions were 28.93, 80 and 28.08 (mg) for X1 ,
      X2 and X3 , respectively, and the response variables were predicted to be 159.8
      nm, 0.241 and 85.8% for Y1 , Y2 and Y3 , respectively. The actual values from the
      optimized formulation showed good agreement with predicted values. The optimized
      TMS-SMEDDS formulation showed faster drug dissolution rate and higher
      bioavailability than TMS powder. CONCLUSIONS: Our results suggest that response
      surface methodology using BBD and desirability function is a promising approach
      to understand the effect of SMEDDS variables and to optimize the formulation.

PMID- 24028612
TI  - Improved percutaneous delivery of ketoprofen using combined application of
      nanocarriers and silicon microneedles.
AB  - OBJECTIVES: The aim of our study was to evaluate the effect of designing
      ketoprofen-loaded nanosized spheres and combining them with solid silicon
      microneedles for enhanced and sustained percutaneous drug delivery. METHODS:
      Ketoprofen-loaded nanoparticles (KET-NP) were designed by modified solvent
      displacement method, using poly (D, L-lactic acid) (PDLLA). All prepared
      nanoparticles were characterised with regard to their particle size distribution,
      morphology, surface properties, thermal behaviour, drug content, drug release and
      stability. In-vitro skin permeation studies were conducted on Franz-type
      diffusion cells using porcine skin treated with ImmuPatch silicon microneedles
      (Tyndall Nation Institute, Cork, Ireland). KEY FINDINGS: The study showed that
      uniform nanospheres were prepared with high encapsulation efficiency and retained
      stable for 2 months. After an initial burst release, the PDLLA nanoparticles were
      capable of sustaining and controlling ketoprofen release that followed Korsmeyer
      Peppas kinetics. An enhanced flux of ketoprofen was observed in the skin treated
      with silicon microneedles over a prolonged period of time. CONCLUSIONS: Following
      application of silicon microneedle arrays, KET-NP were able to enhance ketoprofen
      flux and supply the porcine skin with drug over a prolonged (24 h) period of
      time. Our findings indicate that the delivery strategy described here could be
      used for the further development of effective and painless administration systems
      for sustained percutaneous delivery of ketoprofen.

PMID- 24028613
TI  - Modified-release ointment with nitroglycerin beta-cyclodextrin inclusion complex
      for treatment of anal fissures.
AB  - OBJECTIVES: The aim was to evaluate ointments for local treatment of anal
      fissures. Nitroglycerin (NTG) was complexed with beta-cyclodextrin (beta-CD) to
      provide prolonged NTG release, with the intention of decreasing systemic drug
      absorption and thus reducing side effects. METHODS: Gels, creams and anhydrous
      water-emulsifying (AWE) ointment with NTG-CD were compared with preparations
      containing uncomplexed NTG (diluted with crospovidone, NTG-cP). The in-vitro NTG
      release and ex-vivo skin absorption were studied. KEY FINDINGS: The prolonged
      release ointment with the NTG-CD complex was formulated using AWE base or w/o
      cream (20% water); release of NTG from a hydrogel was very fast with both the
      complexed and uncomplexed forms. From the AWE ointment base, 16.4% or 4.5% of the
      total NTG dose was released after 6 h when NTG-cP or NTG-CD was incorporated,
      respectively. With the complexed form, NTG absorption to the skin after a 5-h
      application was 18.1 or 11.1 MUg/g from AWE ointment or cream, respectively;
      absorption of the uncomplexed NTG was higher: 52.3 or 21.9 MUg/g from AWE
      ointment and cream, respectively. CONCLUSIONS: Complexation with beta-CD results
      in prolonged release of NTG from AWE ointment and w/o cream, which was confirmed
      by the ex-vivo skin absorption results.

PMID- 24028615
TI  - Unravelling the ultrastructure of ascending colon fluids from patients with
      ulcerative colitis by cryogenic transmission electron microscopy.
AB  - OBJECTIVES: Studies on the characterization of ascending colonic fluids are
      scarce, limited to physicochemical characterization of their composition, and
      little is known for the morphology of the produced colloidal phases. In an
      attempt to gain insights for their structure at the ultrastructural level,
      samples from the lumen of ascending colon were collected from patients with
      ulcerative colitis in remission. METHODS: After ultracentrifugation, the
      supernatants of two samples (one with high and one with low cholesterol level)
      were visualized by means of cryogenic transmission electron microscopy. KEY
      FINDINGS: In the supernatants with high cholesterol content, micellar-like
      structures, bilayer fragments, open vesicles, and uni-, bi- and trilamellar
      vesicles were abundant. In addition, crystals of cholesterol were frequently
      observed. In contrast, in the sample with low cholesterol content, oily solids,
      plates of cholesterol monohydrate and elongated structures were present. Few
      unilamellar vesicles were occasionally visualized. CONCLUSIONS: The current study
      gives direct evidence, for the first time, of the existence of 'remnants' of
      lipolytic products in the fasted ascending colon. The impact of these structures
      to colonic absorption of drugs is an open question.

PMID- 24028614
TI  - Comparative evaluation of the degree of pegylation of poly(lactic-co-glycolic
      acid) nanoparticles in enhancing central nervous system delivery of loperamide.
AB  - OBJECTIVES: In this study, we examined the relative cellular uptake of
      nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA)
      polymers with increasing degree of pegylation (PLGA-PEG) and their potential to
      deliver loperamide to the brain of a mouse. METHOD: NPs containing coumarin-6 or
      loperamide HCl were formulated using PLGA and PLGA-PEG, with PEG content of 5
      15%, by the solvent evaporation method. NPs were characterised for size, surface
      charge, morphology, encapsulation efficiency and drug release. Cellular uptake of
      coumarin-6 NPs was examined in Caco-2 monolayers using confocal microscopy and
      central nervous system (CNS) delivery of loperamide HCl from the NPs was examined
      following intranasal administration in a mouse model. KEY FINDINGS: No difference
      in NP characteristics was observed, irrespective of degree of pegylation, except
      for the surface charge which increased with increasing PEG content. PLGA-PEG NPs
      were found to have increased cellular uptake in comparison to PLGA NPs.
      Interestingly, this pattern was reflected in the CNS delivery of loperamide HCl
      in the mouse model. CONCLUSION: The results from this study show that PLGA-PEG
      NPs have the potential to act as carriers for the noninvasive administration of
      therapeutic agents to the brain and possibly across other physiological barriers.

PMID- 24028616
TI  - GPER-1 agonist G1 induces vasorelaxation through activation of epidermal growth
      factor receptor-dependent signalling pathway.
AB  - OBJECTIVES: The G protein-coupled oestrogen receptor-1 (GPER-1) agonist G1
      induces endothelium-dependent relaxation. Activation of the epidermal growth
      factor (EGF) receptor leads to transduction of signals from the plasma membrane
      for the release of nitric oxide. We tested the hypothesis that G1 induces
      endothelium-dependent vasorelaxation through activation of the EGF receptor.
      METHODS: Rat aortic rings were mounted in organ baths. After pretreatment with
      various inhibitors, aortic rings contracted with 11,9-epoxymethano-prostaglandin
      F2alpha or KCl were subjected to relaxation by G1. KEY FINDINGS: G1 induced
      endothelium-dependent vasorelaxation, which was attenuated by pretreatment with
      either L -N(omega) -nitroarginine methyl ester (L -NAME), an inhibitor of nitric
      oxide synthase, or (3aS,4R,9bR)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b
      tetrahydro-3H-cyclopenta[c]quinoline HB-EGF, heparin-binding EGF-like growth
      factor, a GPER-1 antagonist. Neither a general oestrogen receptor antagonist, ICI
      182 780, nor a selective oestrogen receptor-alpha antagonist, methyl-piperidino
      pyrazole dihydrochloride (MPP), had an effect on G1-induced vasorelaxation.
      However, pretreatment with EGF receptor blockers, AG1478 or DAPH, resulted in
      attenuated G1-induced vasorelaxation. In addition, pretreatment with Src
      inhibitor 4-amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo[3,4-d]pyrimidine, 4
      amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine or Akt inhibitor
      VIII also resulted in attenuated vascular relaxation induced by the cumulative
      addition of G1. However, neither phosphatidylinositol-3 kinase inhibitors
      LY294002 and wortmannin nor an extracellular signal-regulated kinase inhibitor
      1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene monoethanolate
      had effect on vascular relaxation induced by the cumulative addition of G1.
      CONCLUSIONS: G1 induces endothelium-dependent vasorelaxation through Src-mediated
      activation of the EGF receptor and the Akt pathway in rat aorta.

PMID- 24028617
TI  - Hepatic and gastrointestinal first-pass effects of vitexin-4"-O-glucoside in
      rats.
AB  - OBJECTIVES: This paper was to clarify the reasons of low bioavailability of
      vitexin-4"-O-glucoside (VOG) in rats via hepatic combined with gastrointestinal
      first-pass effect. METHODS: Observed the hepatic first-pass effect through the
      comparison of area under the plasma concentration-time curve from zero to
      infinity (AUC0->infinity ) of VOG in arterial plasma after femoral and portal
      vein administration (10 mg/kg), similarly, evaluated the gastrointestinal first
      pass effect after portal vein (10 mg/kg) and gastrointestinal administration (20
      mg/kg). For the study on regulatory mechanisms of cytochrome P450 3A (CYP3A) and
      P-glycoprotein (P-gp) on the bioavailability of VOG, the solution of verapamil
      hydrochloride (60 mg/kg) was instilled into intestine at 10 min before the
      infusion of VOG. KEY FINDINGS: The bioavailability of VOG after intraportal,
      intestinal as well as gastric administration was 45.1%, 8.1% and 9.8%,
      respectively. The value of AUC0->infinity for verapamil group was approximately
      1.4-fold higher than that for normal saline group, meaning that perhaps CYP3A
      participated in the metabolism of VOG or P-gp transported VOG outside.
      CONCLUSIONS: The hepatic and intestinal first-pass effect were considered to
      mostly contribute to the low bioavailability of VOG in rats, and the gastric
      first-pass effect should be neglected. Also, the contribution of CYP3A to
      metabolism and P-gp mediated efflux have played a significant role in low
      bioavailability of VOG.

PMID- 24028618
TI  - Modulation of P-glycoprotein in rat brain microvessel endothelial cells under
      oxygen glucose deprivation.
AB  - OBJECTIVES: To investigate modulation of P-glycoprotein (P-gp) in rat brain
      microvessel endothelial cells (rBMECs) under oxygen glucose deprivation (OGD).
      METHODS: The coculture of rBMECs and astrocytes was established to investigate
      the time course of P-gp, tumour necrosis factor-alpha (TNF-alpha), endothelin-1
      (ET-1), nitric oxide synthase (NOS) and protein kinase C (PKC) expression in the
      rBMECs as well as rhodamine 123 (Rh123) transendothelial transfer under OGD using
      Western blot and HPLC, respectively. The influence of pharmacological tools
      including H398, JKC-301, RES-701-1, L-NMMA, BIM and SN50 on the P-gp expression
      as well as Rh123 transendothelial transfer was evaluated at 3 h time point of
      OGD. KEY FINDINGS: Elevated P-gp, TNF-alpha, ET-1, NOS and PKC expression in the
      rBMECs, as well as increased P-gp efflux activity were observed after 2 h or more
      time of OGD. Incubation of H398 and other pharmacological tools downregulated P
      gp expression and functional activity in the rBMECs at 3 h time point of OGD.
      CONCLUSIONS: This report suggested that TNF-alpha, ET-1, NOS and PKC may mediate
      upregulation of P-gp in the rBMECs under OGD, which may be worthy of being
      referenced for the investigation of P-gp at the blood-brain barrier in the early
      period of stroke.

PMID- 24028619
TI  - In-vitro evaluation of chronic alcohol effects on expression of drug-metabolizing
      and drug-transporting proteins.
AB  - OBJECTIVES: In alcoholics without alcoholic liver disease, boosted drug
      elimination has been reported. However, mechanistic explanations for this
      phenomenon remain uncertain. In particular, data on the potential role of drug
      transporters are sparse. METHODS: Using a well-established in-vitro model for
      induction of human drug-metabolizing and drug-transporting proteins, we evaluated
      the potency of ethanol and the major fermentation side-product isopentanol to
      alter expression and function of these proteins by quantitative real-time
      polymerase chain reaction, Western blotting and flow cytometry. P-glycoprotein
      (Pgp)-inhibiting properties of ethanol and isopentanol were investigated via
      calcein extrusion assay. KEY FINDINGS: Ethanol and isopentanol significantly
      changed expression levels of drug-metabolizing and drug-transporting proteins
      that normalized within 2 weeks upon withdrawal. Cytochrome P-450 2C19 and Pgp
      were most strongly induced. Ethanol-induced Pgp at the messenger RNA (mRNA)
      (twofold to eightfold) and protein level (twofold), but not at the functional
      level. Both compounds did not inhibit Pgp. CONCLUSIONS: Ethanol is demonstrated
      to increase mRNA and protein expression of human drug transporters such as Pgp in
      vitro. Withdrawal of ethanol exposure causes return to non-induced conditions
      within weeks. Functional consequences of increased Pgp expression in alcoholics
      need to be evaluated by clinical trials applying selective Pgp substrates such as
      digoxin.

PMID- 24028620
TI  - Baicalin pharmacokinetic profile of absorption process using novel in-vitro
      model: cytochrome P450 3A4-induced Caco-2 cell monolayers combined with rat
      intestinal rinse fluids.
AB  - OBJECTIVES: This study was designed to investigate baicalin (BG) pharmacokinetic
      profile in absorption process using a new model and evaluate the potentiality as
      a new model. METHODS: The effects of BG on intestinal cytochrome P450 3A4 (CYP3A)
      protein/mRNA expression, activity and permeability glycoprotein (P-gp) were
      evaluated in CYP3A4-induced Caco-2 cell monolayers or rats. Intestinal rinse
      fluids (IF) were obtained from rat were added to modified Caco-2 monolayers. KEY
      FINDINGS: Orally administered BG (7 days pretreatment) inhibited intestinal CYP3A
      activity and protein expression. Baicalein (B) converted from BG by IF was
      detected in the upper jejunum in a portion-dependent manner. Subsequently, most
      BG were converted to B in the caecum. In modified Caco-2 monolayers, BG exhibited
      no effect on CYP3A4 activity or mRNA, whereas B and BG treated with IF inhibited
      CYP3A4 transcription and activity. CONCLUSIONS: Intestinal CYP3A was inhibited
      following oral administration of BG to rat. Correspondingly, BG-mediated CYP3A
      inhibition was shown in vitro using modified Caco-2 monolayers treated with IF.
      Hence, in-vivo intestinal absorption pharmacokinetic was reproduced in vitro. IF
      is a key determinant of intestinal absorption, and it facilitated inhibition of
      CYP3A by B, not BG.

PMID- 24028621
TI  - Evaluation for effect of hypothermia on the disposition of 4-nitrophenol in rats
      by in-vitro metabolism study and rat liver perfusion system.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of hypothermia on
      the in-vivo pharmacokinetics of 4-nitrophenol (4NP) using rat liver homogenate
      and rat liver perfusion system. METHODS: Rat liver homogenate was incubated with
      4NP, which is mainly metabolized by cytochrome P450 2E1, at 37, 34, 32 or 28
      degrees C. The Michaelis constant (Km ) and maximum elimination velocity (Vmax )
      of 4NP were calculated by a Hanes-Woolf plot. The hepatic extraction ratio (Eh )
      of 4NP was evaluated in a rat liver perfusion study at 37, 34, 32 or 28 degrees
      C. Moreover, the plasma concentration profiles of 4NP after its intravenous
      (i.v.) administration to rats were analysed by the moment theory and were
      compared with in-vitro parameters. KEY FINDINGS: While the Km of 4NP was not
      changed, the Vmax and Eh were reduced at low temperatures. The plasma
      concentrations of 4NP after its i.v. administration to rats were significantly
      increased at 28 degrees C. CONCLUSION: Changes in the pharmacokinetics of 4NP
      under hypothermic conditions were caused by alterations in Vmax and Eh . We may
      be able to predict the disposition of a drug by in-vitro studies.

PMID- 24028622
TI  - Exploring QSAR and pharmacophore mapping of structurally diverse selective matrix
      metalloproteinase-2 inhibitors.
AB  - OBJECTIVES AND METHODS: Matrix metalloproteinase-2 (MMP-2) is a potential target
      in metastases. Regression (conventional 2D QSAR) and classification (recursive
      partitioning (RP), Bayesian modelling) QSAR, pharmacophore mapping and 3D QSAR
      (comparative molecular field analysis and comparative molecular similarity
      analysis) were performed on 202 MMP-2 inhibitors. KEY FINDINGS: Quality of the
      regression models was justified by internal (Q(2) ) and external (R(2) Pred )
      cross-validation parameters. Stepwise regression was used to develop linear model
      (Q(2)  = 0.822, R(2) Pred  = 0.667). Genetic algorithm developed linear (Q(2)  =
      0.845, R(2) Pred  = 0.638) and spline model (Q(2)  = 0.882, R(2) Pred  = 0.644).
      The RP and Bayesian models showed cross-validated area under receiver operating
      characteristic curve (AUCROC _ CV ) of 0.805 and 0.979 respectively. QSAR models
      depicted importance of descriptors like five-membered rings, fractional
      positively charged surface area, lipophilocity and so on. Higher molecular volume
      was found to be detrimental. Pharmacophore mapping was performed with two tools -
      Hypogen and PHASE. Both models indicated that one hydrophobic and three hydrogen
      bond acceptor features are essential. The Pharmacophore-aligned structures were
      used for CoMFA (Q(2) of 0.586 and R(2) Pred of 0.689) and CoMSIA (Q(2) of 0.673
      and R(2) Pred of 0.758), results of which complied with the other analyses.
      CONCLUSIONS: All modelling techniques were compared to each other. The current
      study may help in designing novel MMP-2 inhibitors.

PMID- 24028623
TI  - Dietary supplementation with Salvia sahendica attenuates acetylcholinesterase
      activity and increases mitochondrial transcription factor A and antioxidant
      proteins in the hippocampus of amyloid beta-injected rats.
AB  - OBJECTIVES: We evaluated the acetylcholinesterase (AChE) inhibitory and potential
      antioxidant effects of Salvia sahendica extract to investigate whether these
      molecules are involved in learning and memory improvement in rats injected with
      fibrillar amyloid beta (Abeta) peptide in the CA1 region of their hippocampus.
      METHODS: Rats were fed with S. sahendica (100 mg/kg/day) for 1 week before Abeta
      injection. Western blot analysis and enzymatic assays were carried out 7 days
      after injections. KEY FINDINGS: Our results indicated that S. sahendica extract
      decreased AChE activity. Besides, S. sahendica prevented reduction in the level
      of nuclear respiratory factor-1 and mitochondrial transcription factor A (TFAM).
      Our data indicated the lack of sensitivity in citrate synthase and reduction in
      the activity of malate dehydrogenase in the presence of Abeta that was prevented
      with S. sahendica consumption. Pretreatment with S. sahendica extract impeded
      reduction of glutathione redox ratio, catalase and superoxide dismutase activity,
      while decreased the malondialdehyde level. CONCLUSIONS: Based on the importance
      of AChE activity inhibition and increased TFAM level in the prevention of
      cognitive impairment, the use of S. sahendica could open a new protective issue
      in therapeutic fields of neurodegenerative disease.

PMID- 24028624
TI  - Cucurbita ficifolia Bouche (Cucurbitaceae) and D-chiro-inositol modulate the
      redox state and inflammation in 3T3-L1 adipocytes.
AB  - OBJECTIVES: Cucurbita ficifolia (characterised by its D chiro inositol (DCI)
      content) and of synthetic DCI on the redox state, mRNA expression and secretions
      of proinflammatory cytokines. Additionally, we evaluated the insulin-mimetic
      action of both treatments by assessing protein kinase B (PKB) activation in 3T3
      L1 adipocytes. METHODS: Adipocytes were treated with C. ficifolia and synthetic
      DCI. The redox state was determined by spectrophotometry as changes in the
      reduced glutathione/oxidised glutathione (GSH/GSSG) ratio, glutathione peroxidase
      and glutathione reductase activities; H2 O2 levels were measured by flow
      cytometry. The mRNA expression and the protein level of cytokines were
      determinate by real-time reverse transcription polymerase chain reaction and
      enzyme-linked immunosorbent assay, respectively. The activation of PKB activation
      was detected by Western blot. KEY FINDINGS: C. ficifolia extract and synthetic
      DCI reduced oxidative stress by decreased H2 O2 levels, increased glutathione
      peroxidase activity and changes in the GSH/GSSG ratio. Furthermore, DCI decreased
      the mRNA expression and secretion of tumour necrosis factor-alpha, interleukin 6
      (IL-6) and resistin, while C. ficifolia reduced protein levels of resistin and
      increased IL-6 levels. Only DCI demonstrated insulin-mimetic action. CONCLUSIONS:
      The antioxidant and anti-inflammatory effects of C. ficifolia extract can be
      explained in part by its DCI content, which modulates the GSH/GSSG ratio and
      contributes to a reduced proinflammatory state. C. ficifolia and DCI treatments
      may reduce the disturbances caused by oxidative stress. Additionally, DCI may
      improve insulin sensitivity through its insulin-mimetic effects.

PMID- 24028625
TI  - Should we rely on the Kenward-Roger approximation when using linear mixed models
      if the groups have different distributions?
AB  - The study explores the robustness to violations of normality and sphericity of
      linear mixed models when they are used with the Kenward-Roger procedure (KR) in
      split-plot designs in which the groups have different distributions and sample
      sizes are small. The focus is on examining the effect of skewness and kurtosis.
      To this end, a Monte Carlo simulation study was carried out, involving a split
      plot design with three levels of the between-subjects grouping factor and four
      levels of the within-subjects factor. The results show that: (1) the violation of
      the sphericity assumption did not affect KR robustness when the assumption of
      normality was not fulfilled; (2) the robustness of the KR procedure decreased as
      skewness in the distributions increased, there being no strong effect of
      kurtosis; and (3) the type of pairing between kurtosis and group size was shown
      to be a relevant variable to consider when using this procedure, especially when
      pairing is positive (i.e., when the largest group is associated with the largest
      value of the kurtosis coefficient and the smallest group with its smallest
      value). The KR procedure can be a good option for analysing repeated-measures
      data when the groups have different distributions, provided the total sample
      sizes are 45 or larger and the data are not highly or extremely skewed. 

PMID- 24028626
TI  - Resolution of five-component mixture using mean centering ratio and inverse least
      squares chemometrics.
AB  - BACKGROUND: A comparative study of the use of mean centering of ratio spectra and
      inverse least squares for the resolution of paracetamol, methylparaben,
      propylparaben, chlorpheniramine maleate and pseudoephedrine hydrochloride has
      been achieved showing that the two chemometric methods provide a good example of
      the high resolving power of these techniques. Method (I) is the mean centering of
      ratio spectra which depends on using the mean centered ratio spectra in four
      successive steps that eliminates the derivative steps and therefore the signal to
      noise ratio is improved. The absorption spectra of prepared solutions were
      measured in the range of 220-280 nm. Method (II) is based on the inverse least
      squares that depend on updating developed multivariate calibration model. The
      absorption spectra of the prepared mixtures in the range 230-270 nm were
      recorded. RESULTS: The linear concentration ranges were 0-25.6, 0-15.0, 0-15.0, 0
      45.0 and 0-100.0 MUg mL-1 for paracetamol, methylparaben, propylparaben,
      chlorpheniramine maleate and pseudoephedrine hydrochloride, respectively. The
      mean recoveries for simultaneous determination were between 99.9-101.3% for the
      two methods. The two developed methods have been successfully used for prediction
      of five-component mixture in Decamol Flu syrup with good selectivity, high
      sensitivity and extremely low detection limit. CONCLUSION: No published method
      has been reported for simultaneous determination of the five components of this
      mixture so that the results of the mean centering of ratio spectra method were
      compared with those of the proposed inverse least squares method. Statistical
      comparison was performed using t-test and F-ratio at P = 0.05. There was no
      significant difference between the results.

PMID- 24028627
TI  - 7-ketocholesterol-induced caspase-mediated apoptosis in Saccharomyces cerevisiae.
AB  - The cytotoxicity of cholesterol oxidation products has been documented in several
      mammalian cell lines. It can lead to a wide range of diseases. However, the
      molecular mechanisms underlying this toxicity in vivo are scarce. The objective
      of the present study was to assess the potential toxic effects of 7
      ketocholesterol, an important cholesterol oxidation product, on Saccharomyces
      cerevisiae. Our data show for the first time that 7-ketocholesterol can induce
      dose-dependent cell death in S. cerevisiae. These results suggest that the death
      induced by this compound is apoptotic and accompanied by chromatin condensation,
      the production of ROS, and translocation of phosphatidylserine from the inner to
      the outer leaflet of the cytoplasmic membrane. We further showed that 7
      ketocholesterol-induced cell death was partially rescued after pretreatment with
      caspase inhibitor (Z-VAD-fmk). In addition, caspase deletion resulted in
      promotion of cell viability. All these results strongly indicated that 7
      ketocholesterol induces apoptosis in yeast cells through a caspase-dependent
      pathway.

PMID- 24028628
TI  - Novel potential inhibitors for adenylylsulfate reductase to control souring of
      water in oil industries.
AB  - The biogenic production of hydrogen sulfide gas by sulfate-reducing bacteria
      (SRB) causes serious economic problems for natural gas and oil industry. One of
      the key enzymes important in this biologic process is adenosine phosphosulfate
      reductase (APSr). Using virtual screening technique we have discovered 15
      compounds that are novel potential APSr inhibitors. Three of them have been
      selected for molecular docking and microbiological studies which have shown good
      inhibition of SRB in the produced water from the oil industry. 

PMID- 24028629
TI  - Saccharomyces boulardii for prevention of necrotizing enterocolitis in preterm
      infants: a randomized, controlled study.
AB  - AIM: To evaluate the efficacy of orally administered Saccharomyces boulardii (S.
      boulardii) for reducing the incidence and severity of necrotizing enterocolitis
      (NEC) in very low-birth-weight (VLBW) infants. METHODS: A prospective, randomised
      controlled trial was conducted in infants with gestational age <=32 weeks and
      birth weight <=1500 g. The study group received S. boulardii supplementation, and
      the control group did not. The primary outcomes were death or NEC (Bell's stage
      >=2), and secondary outcomes were feeding intolerance and clinical or culture
      proven sepsis. RESULTS: A total of 271 infants were enrolled in the study, 135 in
      the study group and 136 in the control group. There was no significant difference
      in the incidence of death (3.7% vs. 3.6%, 95% CI of the difference, -5.20-5.25; p
      = 1.0) or NEC (4.4% vs. 5.1%, 95% CI, -0.65-5.12; p = 1.0) between the groups.
      However, feeding intolerance and clinical sepsis were significantly lower in the
      probiotic group compared with control. CONCLUSION: Although Saccharomyces
      boulardii supplementation at a dose of 250 mg/day was not effective at reducing
      the incidence of death or NEC in VLBW infants, it improved feeding tolerance and
      reduced the risk of clinical sepsis.

PMID- 24028630
TI  - Magnitude and mechanism of charge enhancement of CH..O hydrogen bonds.
AB  - Quantum calculations find that neutral methylamines and thioethers form
      complexes, with N-methylacetamide (NMA) as proton acceptor, with binding energies
      of 2-5 kcal/mol. This interaction is magnified by a factor of 4-9, bringing the
      binding energy up to as much as 20 kcal/mol, when a CH3(+) group is added to the
      proton donor. Complexes prefer trifurcated arrangements, wherein three separate
      methyl groups donate a proton to the O acceptor. Binding energies lessen when the
      systems are immersed in solvents of increasing polarity, but the ionic complexes
      retain their favored status even in water. The binding energy is reduced when the
      methyl groups are replaced by longer alkyl chains. The proton acceptor prefers to
      associate with those CH groups that are as close as possible to the S/N center of
      the formal positive charge. A single linear CH..O hydrogen bond (H-bond) is less
      favorable than is trifurcation with three separate methyl groups. A trifurcated
      arrangement with three H atoms of the same methyl group is even less favorable.
      Various means of analysis, including NBO, SAPT, NMR, and electron density shifts,
      all identify the (+)CH..O interaction as a true H-bond. 

PMID- 24028631
TI  - Bed rest duration after sheath removal following percutaneous coronary
      interventions: a systematic review and meta-analysis.
AB  - AIMS AND OBJECTIVES: To explore the effect of bed rest duration after sheath
      removal following percutaneous coronary interventions on the incidence of
      vascular complications, back pain and urinary problems. BACKGROUND: According to
      the literature, the duration of bed rest after sheath removal following
      percutaneous coronary interventions ranges from 2-24 hours. Several studies have
      assessed the effect of duration of bed rest on vascular complications, but a
      clear final conclusion about the exact duration of bed rest has not been reached.
      DESIGN: Systematic review and meta-analysis. METHODS: Cochrane Library, MEDLINE,
      SCOPUS, CINAHL, IranMedex and IranDoc were searched. No language limitation was
      applied. RCTs that used two different periods for ambulation were included. Two
      reviewers separately assessed the quality of each included study and extracted
      the data. Dichotomous outcomes were recorded as odds ratio with 95% confidence
      interval. RESULTS: Five studies involving 1115 participants were included in the
      review. Among them, two studies had three comparison groups. The studies
      considered a variety of periods as early and late ambulation, ranging from 2-10
      hours. Totally, there were no statistically significant differences in the
      incidence of bleeding, pseudoaneurysm, arteriovenous fistula and urinary problems
      between early and late ambulation. There was a statistically significant
      reduction in the risk of haematoma formation at four to six hours of bed rest
      compared with eight hours of bed rest (odds ratio = 0.37, 95% CI: 0.15, 0.91).
      Back pain was reported in one study evaluating three hours of bed rest with an
      odds ratio of 0.45 (95% confidence interval: 0.28, 0.71) when compared with 10
      hours of bed rest. CONCLUSIONS: Early ambulation after percutaneous coronary
      interventions is safe and feasible; however, the results should be used with
      caution as the majority of included studies had methodological flaws. RELEVANCE
      TO CLINICAL PRACTICE: The results of this study suggest that patients could be
      ambulated three to four hours after sheath removal following percutaneous
      coronary interventions and early ambulation dose does not increase the risk of
      vascular complications, but it moderates back pain occurrence.

PMID- 24028632
TI  - Gender equality as a means to improve maternal and child health in Africa.
AB  - In this article we examine whether measures of gender equality, household
      decision making, and attitudes toward gender-based violence are associated with
      maternal and child health outcomes in Africa. We pooled Demographic and Health
      Surveys data from eight African countries and used multilevel logistic regression
      on two maternal health outcomes (low body mass index and facility delivery) and
      two child health outcomes (immunization status and treatment for an acute
      respiratory infection). We found protective associations between the gender
      equality measures and the outcomes studied, indicating that gender equality is a
      potential strategy to improve maternal and child health in Africa. 

PMID- 24028634
TI  - Should we test all defibrillators at the time of implantation? An unanswered
      question.

PMID- 24028633
TI  - Strong population genetic structuring in an annual fish, Nothobranchius furzeri,
      suggests multiple savannah refugia in southern Mozambique.
AB  - BACKGROUND: Intraspecific genetic variation of African fauna has been
      significantly affected by pronounced climatic fluctuations in Plio-Pleistocene,
      but, with the exception of large mammals, very limited empirical data on
      diversity of natural populations are available for savanna-dwelling animals.
      Nothobranchius furzeri is an annual fish from south-eastern Africa, inhabiting
      discrete temporary savannah pools outside main river alluvia. Their dispersal is
      limited and population processes affecting its genetic structure are likely a
      combination of those affecting terrestrial and aquatic taxa. N. furzeri is a
      model taxon in ageing research and several populations of known geographical
      origin are used in laboratory studies. Here, we analysed the genetic structure,
      diversity, historical demography and temporal patterns of divergence in natural
      populations of N. furzeri across its entire distribution range. RESULTS: Genetic
      structure and historical demography of N. furzeri were analysed using a
      combination of mitochondrial (partial cytochrome b sequences, 687 bp) and nuclear
      (13 microsatellites) markers in 693 fish from 36 populations. Genetic markers
      consistently demonstrated strong population structuring and suggested two main
      genetic groups associated with river basins. The split was dated to the Pliocene
      (>2 Mya). The northern group inhabits savannah pools across the basin of the
      intermittent river Chefu in south-western Mozambique and eastern Zimbabwe. The
      southern group (from southernmost Mozambique) is subdivided, with the River
      Limpopo forming a barrier (maximum divergence time 1 Mya). A strong habitat
      fragmentation (isolated temporary pools) is reflected in significant genetic
      structuring even between adjacent pools, with a major influence of genetic drift
      and significant isolation-by-distance. Analysis of historical demography revealed
      that the expansion of both groups is ongoing, supported by frequent founder
      effects in marginal parts of the range and evidence of secondary contact between
      Chefu and Limpopo populations. CONCLUSIONS: We demonstrated: (1) ancient (pre
      Pleistocene) divergence between the two main N. furzeri lineages, their recent
      secondary contact and lack of reproductive isolation; (2) important genetic
      structuring attributed to the fragmented nature of their environment and
      isolation-by-distance, suggesting that dispersal is limited, occurs over short
      distances and is not directly associated with river routes; (3) an apparent role
      of the River Limpopo as a barrier to dispersal and gene flow.

PMID- 24028635
TI  - Tea polyphenols as novel and potent inhibitory substances against renin activity.
AB  - Renin inhibitory activities of three tea products were investigated for the first
      time in this work. Water extracts from fermented oolong and black tea showed
      strong renin inhibitory activities. By the means of ultrafiltration, gradient
      high performance liquid chromatography and spectroscopic analysis, four active
      compounds were separated from aqueous black tea extract and identified as
      theasinensin B, theasinensin C, strictinin, and a hexose sulfate with a galloyl
      moiety, which had IC50 values of 19.33, 40.21, 311.09, and 50.16 MUM against
      renin activity, respectively. Further detection indicated that the potent
      inhibitor theasinensin B was present only in black tea, and that monomeric
      catechins did not contribute significantly to the renin inhibitory activities of
      tea products. These results revealed novel and potent tea-derived renin
      inhibitors and suggested another potential pathway for tea consumption to control
      hypertension. 

PMID- 24028636
TI  - Ex vivo dermatoscopy of scalp specimens and slides.
AB  - BACKGROUND: Correct evaluation of horizontal scalp biopsies requires accurate
      gross sectioning and embedding of the tissue. The most common issue during
      processing includes incorrect specimen bisection. OBJECTIVES: To verify if (i) ex
      vivo assessment of scalp biopsies by contact dermatoscopy can identify the
      correct plane of transverse bisection as well as (ii) if using contact
      dermatoscopy on the glass slides can be useful to control the tissue processing
      and expedite sign-out. MATERIALS AND METHODS: For the first aim, dermatoscopic
      pictures of 43 scalp biopsies were printed and shown to 10 dermatology residents
      not involved in the study, who were asked to identify and highlight the dermo
      epidermal junction. For the second aim, dermatoscopic captions of 40 horizontal
      sections were evaluated in a blinded way for the size of the specimen as well as
      the level and plane of bisection. The agreement was investigated using Cohen's
      kappa statistics. RESULTS: Ten independent observers were able to correctly
      identify the dermo-epidermal junction as a brownish wavy line in 95.3% cases. The
      Cohen's kappa statistics showed almost perfect agreement. Two independent
      pathologists agreed on the specimen size in all cases, on the specimen plane in
      39 cases and on the specimen level on 35 cases. The Cohen's kappa statistics
      showed almost complete agreement for the size and plane of bisection and
      substantial agreement for the level of section. CONCLUSION: Ex vivo dermatoscopy
      of scalp biopsies may be a new way to decrease laboratory costs and improve
      turnaround time in hair pathology as this technique optimally guides the correct
      bisection at 1-1.5 mm below the junction. Ex vivo dermatoscopy on the slides may
      expedite sign out after the initial bisection.

PMID- 24028638
TI  - Quantitative evaluation of interstitial fibrosis with Sirius Red in IgA
      nephritis.
AB  - OBJECTIVE: Tubulointerstitial fibrosis is one of the strongest independent
      predictive factors in determining the prognosis in IgA nephritis. Recently,
      software-based quantitative measurement of interstitial fibrosis with Sirius Red
      staining has entered the practice. The objective of this study was to investigate
      the prognostic value of measurement of interstitial nephritis with this method in
      IgA nephritis. METHOD: Forty-three patients diagnosed with IgA nephritis with
      renal biopsy between the years 2005 and 2009 were included in this retrospective
      observational study. The diagnostic biopsies of 37 patients were examined. Basal
      data included age, gender, creatinine level, glomerular filtration rate (GFR),
      presence of proteinuria, hypertension, glomerulosclerosis, mesangial
      proliferation, and interstitial fibrosis and fibrosis index calculated by the
      measurement of computed images of Sirius Red positive areas. Final visit included
      evaluation of development of end-stage renal disease (ESRD), and GFR (whether =
      60 mL/min or <60 mL/min). RESULTS: Numbers of patients with hypertension (75% vs.
      34.5%; p = 0.050), ESRD development (62.5% vs. 20.7%, p = 0.035), GFR <60 mL/min
      (87.5% vs. 31%; p = 0.007) were greater; and basal GFR (34.25 +/- 25.29 vs. 64.14
      +/- 35.34; p = 0.048) was lower in high-intensity interstitial fibrosis group
      (>1000 MUm2) compared to low-intensity interstitial fibrosis group (<=1000
      MUm(2)). CONCLUSION: Quantitative analysis of computed imaging of areas of Sirius
      Red positive tubulointerstitial fibrosis might serve as an effective novel method
      to determine the prognosis in IgA nephritis.

PMID- 24028639
TI  - Orthostatic responses at 4860 m in low, moderate, and high altitude residents.
AB  - This study evaluated the influence of altitude of residence on orthostatic
      responses when exposed to high altitude. Data collection took place at the Carrel
      hut (4860 m) on Chimborazo in Ecuador. After being transported to the hut by
      vehicle, 69 people volunteered for the study. A 3-min stand test (rapid change
      from supine to standing) provided an orthostatic challenge while resting heart
      rate (RHR), systolic (SBP) and diastolic (DBP) blood pressures, and arterial
      oxygen saturation (SpO2) were measured. Participants were separated into four
      groups based on altitude of residence and ethnicity: LOW (<1500 m; n=15), MOD
      (1500-3000 m, n=30), and HIGH (>3000 m, n=11) Ecuadorians, and non-Ecuadorian
      lowlanders (NE-LOW, n=13). Supine and standing RHRs were lower (p<0.05) for HIGH
      compared to other groups. Furthermore, standing increased RHR in LOW, MOD, and NE
      LOW by 11.9 +/- 5.3, 9.5 +/- 4.1, and 11.6 +/- 7.4 bpm, respectively, while HIGH
      stayed the same (0.6 bpm increase +/- 3.3). Additionally, mean arterial pressure
      decreased slightly but not significantly upon standing in all groups except HIGH.
      The difference in Spo2 among groups was not significant (p>0.05). Altitude of
      residence influences the cardiovascular responses to orthostatic stress with HIGH
      having blunted responses and greater tolerance.

PMID- 24028640
TI  - Cyclic hypobaric hypoxia improves markers of glucose metabolism in middle-aged
      men.
AB  - Chronic hypoxia increases dependence on glucose in men and increases insulin
      sensitivity in men and women. Cyclic Variations in Altitude Conditioning (CVAC)
      is a novel technology that provides exposure to rapidly fluctuating cyclic
      hypobaric hypoxia (CHH). PURPOSE: To test the hypothesis that markers of glucose
      metabolism would change with CVAC CHH, two groups of middle-aged men were exposed
      to 10 weeks (40 min/day, 3 day/week) of either CHH or sham (SH) sessions.
      METHODS: CHH subjects (age: 48 +/- 6, weight: 86 +/- 12 kg, BMI: 27.1 +/- 3,
      n=11) experienced cyclic pressures simulating altitudes ranging from sea level to
      3048 m (week 1) and progressing to 6096 m (by week 5 through week 10). SH
      subjects (age: 50 +/- 4, weight: 89 +/- 15 kg, BMI: 27.5 +/- 3, n=10) were
      exposed to slowly-fluctuating pressures up to 607 m (all subjects blinded to
      elevation). Physical function and blood markers of glucose metabolism were
      measured at baseline, 3, 6, and 10 weeks. RESULTS: Two CHH subjects were dropped
      from analysis for failure to progress past 3048 m (CHH: n=9). Weight and physical
      activity remained stable for both groups. There was a group-by-time interaction
      in fasting glucose (CHH: 96 +/- 9 to 91 +/- 7 mg/dL, SH: 94 +/- 7 to 97 +/- 9
      mg/dL, p<0.05). Reduction in plasma glucose response to oral glucose tolerance
      test [area under the curve] was greater in CHH compared to SH after 10 weeks of
      exposure (p<0.03). Neither group experienced changes in fasting insulin, insulin
      response during the OGTT, or changes in a timed walk test. CONCLUSION: Ten weeks
      of CVAC CHH exposure improves markers of glucose metabolism in middle-aged men at
      risk for metabolic syndrome.

PMID- 24028641
TI  - Mountaineering fatalities on Aconcagua: 2001-2012.
AB  - High altitude mountaineering is a dangerous endeavor due to the hypoxic hypobaric
      environment, extreme weather, and technical skills required. One of the seven
      summits, Aconcagua (6962 m) is the highest mountain outside of Asia. Its most
      popular route is nontechnical, attracting >3000 mountaineers annually. Utilizing
      data from the Servicio Medico Aconcagua (park medical service), we performed a
      retrospective descriptive analysis with the primary objective of deriving a
      fatality rate on Aconcagua from 2001 to 2012. The fatality rate on Aconcagua was
      then compared to other popular mountains. For climbers who died, we report all
      available demographic data, mechanisms of death, and circumstances surrounding
      the death. Between 2001 and 2012, 42,731 mountaineers attempted to summit
      Aconcagua. There were 33 fatalities. The fatality rate was 0.77 per 1000, or
      0.077%. The fatality rate on Aconcagua is lower than that on Everest or Denali
      but higher than that on Rainier.

PMID- 24028642
TI  - Tissue oxygenation and mitochondrial respiration under different modes of
      intermittent hypoxia.
AB  - We compared the results of five modes of intermittent hypoxia training (IHT) on
      gastrocnemius muscle Po2 and heart and liver mitochondrial respiration in rats.
      Minutes of hypoxia, %O2, and recovery minutes on air in each mode were: 1) 5,
      12%, 5; 2) 15, 12%, 15; 3) 5, 12%, 15; 4) 5, 7%, 5; and 5) 5, 7%, 15. Mode 1
      proved best in that Pmo2 dropped minimally at the end of every hypoxic bout and
      recovered quickly after each bout. One, 2, and 3 week IHT in mode 1 each
      increased tissue PO2 in both normoxic and 30 min severe hypoxic (7% O2) tests.
      Adaptation to IHT in Mode 1 caused the substrate-dependent reorganization of
      liver and heart mitochondrial energy metabolism favoring NADH-dependent oxidation
      and improving the efficiency of oxidative phosphorylation. Mitochondrial
      adaptation occurred after 14 days of IHT in liver tissue, but after 21 days in
      myocardium, and was preserved during the 3 months following IHT termination. When
      using Mode 2, positive changes were also registered, but were less pronounced.
      Other IHT modes provoked negative effects on Pmo2 levels, both during hypoxic
      periods and reoxygenation. In conclusion, the most effective IHT regimen is 5 min
      12% O2 with 5 min breaks, five cycles per day during 2 or 3 weeks depending on
      the task of IHT.

PMID- 24028644
TI  - The Hypoxia Symposium 2013.

PMID- 24028637
TI  - Bacteria and endotoxin in meconium-stained amniotic fluid at term: could intra
      amniotic infection cause meconium passage?
AB  - BACKGROUND: Meconium-stained amniotic fluid (MSAF) is a common occurrence among
      women in spontaneous labor at term, and has been associated with adverse outcomes
      in both mother and neonate. MSAF is a risk factor for microbial invasion of the
      amniotic cavity (MIAC) and preterm birth among women with preterm labor and
      intact membranes. We now report the frequency of MIAC and the presence of
      bacterial endotoxin in the amniotic fluid of patients with MSAF at term.
      MATERIALS AND METHODS: We conducted a cross-sectional study including women in
      presumed preterm labor because of uncertain dates who underwent amniocentesis,
      and were later determined to be at term (n = 108). Patients were allocated into
      two groups: (1) MSAF (n = 66) and (2) clear amniotic fluid (n = 42). The presence
      of bacteria was determined by microbiologic techniques, and endotoxin was
      detected using the Limulus amebocyte lysate (LAL) gel clot assay. Statistical
      analyses were performed to test for normality and bivariate comparisons. RESULTS:
      Bacteria were more frequently present in patients with MSAF compared to those
      with clear amniotic fluid [19.6% (13/66) versus 4.7% (2/42); p < 0.05]. The
      microorganisms were Gram-negative rods (n = 7), Ureaplasma urealyticum (n = 4),
      Gram-positive rods (n = 2) and Mycoplasma hominis (n = 1). The LAL gel clot assay
      was positive in 46.9% (31/66) of patients with MSAF, and in 4.7% (2/42) of those
      with clear amniotic fluid (p < 0.001). After heat treatment, the frequency of a
      positive LAL gel clot assay remained higher in the MSAF group [18.1% (12/66)
      versus 2.3% (1/42), p < 0.05]. Median amniotic fluid IL-6 concentration (ng/mL)
      was higher [1.3 (0.7-1.9) versus 0.6 (0.3-1.2), p = 0.04], and median amniotic
      fluid glucose concentration (mg/dL) was lower [6 (0-8.9) versus 9 (7.4-12.6), p <
      0.001] in the MSAF group, than in those with clear amniotic fluid. CONCLUSION:
      MSAF at term was associated with an increased incidence of MIAC. The index of
      suspicion for an infection-related process in postpartum women and their neonates
      should be increased in the presence of MSAF.

PMID- 24028643
TI  - A randomized trial of temazepam versus acetazolamide in high altitude sleep
      disturbance.
AB  - This study is the first comparative trial of sleep medications at high altitude.
      We performed a randomized, double-blind trial of temazepam and acetazolamide at
      an altitude of 3540 meters. 34 healthy trekkers with self-reports of high
      altitude sleep disturbance were randomized to temazepam 7.5 mg or acetazolamide
      125 mg taken at bedtime for one night. The primary outcome was sleep quality on a
      100 mm visual analog scale. Additional measurements were obtained with
      actigraphy; pulse oximetry; and questionnaire evaluation of sleep, daytime
      drowsiness, daytime sleepiness, and acute mountain sickness. Sixteen subjects
      were randomized to temazepam and 18 to acetazolamide. Sleep quality on the 100 mm
      visual analog scale was higher for temazepam (59.6, SD 20.1) than acetazolamide
      (46.2, SD 20.2; p=0.048). Temazepam also demonstrated higher subjective sleep
      quality on the Groningen Sleep Quality Scale (3.5 vs. 6.8, p=0.009) and sleep
      depth visual analog scale (60.3 vs. 41.4, p=0.028). The acetazolamide group
      reported significantly more awakenings to urinate (1.8 vs. 0.5, p=0.007). No
      difference was found with regards to mean nocturnal oxygen saturation (84.1 vs.
      84.4, p=0.57), proportion of the night spent in periodic breathing, relative
      desaturations, sleep onset latency, awakenings, wake after sleep onset, sleep
      efficiency, Stanford Sleepiness Scale scores, daytime drowsiness, or change in
      self-reported Lake Louise Acute Mountain Sickness scores. We conclude that, at
      current recommended dosing, treatment of high-altitude sleep disturbance with
      temazepam is associated with increased subjective sleep quality compared to
      acetazolamide.

PMID- 24028645
TI  - Activation of transient receptor potential vanilloid 1 decreases endothelial
      nitric oxide synthase phosphorylation at Thr497 by protein phosphatase 2B
      dependent dephosphorylation of protein kinase C.
AB  - AIMS: We investigated the effects and underlying molecular mechanism of transient
      receptor potential vanilloid 1 (TRPV1), a calcium (Ca(2+) )-permeable non
      selective cation channel, on phosphorylation of endothelial nitric oxide synthase
      (eNOS) at threonine 497 (Thr497) in bovine aortic endothelial cells (BAECs) and
      in mice. METHODS: Western blotting and immunoprecipitation were used for the
      evaluation of protein phosphorylation; protein phosphatase 2B (PP2B) activity was
      assessed by convention kit; Griess assay was for NO production; tube formation
      and Matrigel plug assay were used for angiogenesis. RESULTS: In BAECs, treatment
      with the TRPV1 ligand evodiamine decreased the phosphorylation of eNOS at Thr497,
      protein kinase Calpha (PKCalpha) at Serine 657 (Ser657) and PKCbeta2 at Ser660.
      Evodiamine increased protein phosphatase 2B (PP2B) activity and promoted the
      formation of a PP2B-PKC complex. Inhibition of TRPV1 activation by the
      pharmacological antagonists, removal of extracellular Ca(2+) or pharmacological
      inhibition of PI3K/Akt/calmodulin-dependent protein kinase II/AMP-activated
      protein kinase signalling pathway abolished the evodiamine-induced alterations in
      phosphorylation of eNOS at Thr497, PKCalpha at Ser657, PKCbeta2 at Ser660 and
      PP2B activity, as well as the formation of a PP2B-PKC complex. Inhibition of PP2B
      activation partially reduced the evodiamine-induced NO bioavailability and tube
      formation in endothelial cells (ECs) and angiogenesis in mice. Moreover,
      evodiamine decreased the phosphorylation of eNOS at Thr497, PKCalpha at Ser657
      and PKCbeta2 at Ser660 in apolipoprotein E (ApoE)-deficient mouse aortas but not
      TRPV1-deficient or ApoE/TRPV1 double-knockout mice. CONCLUSION: TRPV1 activation
      in ECs may elicit a Ca(2+) -dependent effect on PP2B-PKC signalling, which leads
      to dephosphorylation of eNOS at Thr497 in ECs and in mice.

PMID- 24028646
TI  - Effect of testosterone replacement therapy on cardiac performance and oxidative
      stress in orchidectomized rats.
AB  - AIM: To investigate the effects of testosterone on myocardial contractility,
      oxidative stress status and expression of sodium channel protein (Nav1.5) and
      inward rectifying K channels (Kir 2.x) in normal and orchidectomized (ORX) rats.
      METHODS: One hundred four rats were randomly assigned into four groups (n = 26,
      each) as follows: (i) untreated controls, (ii) testosterone treated, (iii)
      orchidectomized rats and (iv) orchidectomized, testosterone-treated rats.
      Treatments with the vehicle or testosterone were carried out for 12 weeks, three
      times per week. At the end of treatment, surface ECG, isolated heart, tissue
      oxidative stress and lipid peroxidation experiments were carried out on the
      cardiac tissues. Also, immunohistochemical examination for Nav1.5 and PCR
      detection of mRNA of Kir2.1, Kir2.2 and Kir2.4 subunits of K channels were
      carried out. RESULTS: Orchidectomy impaired cardiac contractile function
      parameters left ventricular developed pressure (LVDP) and the peaks of the
      positive and negative pressure derivatives (dP/dtmax and -dP/dtmax respectively),
      increased heart rate and prolonged QT and QTc intervals, elevated pro-oxidant
      state in rat's hearts and decreased the expression of Kir 2.1 but not Kir2.2, Kir
      2.4 and Nav1.5 channels. Exogenous testosterone administration to orchidectomized
      rats restored heart contractility and shortened QT and QTc intervals to their
      normal values, ameliorated the generated pro-oxidant state and improved the
      expression of Nav1.5 and Kir2.1, but not Kir2.2 or Kir2.4 channels. CONCLUSION:
      Testosterone improved cardiac contractility and shortened QT and QTc intervals in
      ORX rats. An effect that might be dependent of reduction in oxidative stress and
      enhancement of Kir2.1 channels but independent of Nav1.5 channel protein.

PMID- 24028647
TI  - Small bowel strictures in Crohn's disease: a quantitative investigation of
      intestinal motility using MR enterography.
AB  - BACKGROUND: Intestinal stricturing and aberrant small bowel motility are common
      complications in patients with Crohn's disease (CD) leading to significant
      morbidity. A retrospective study was performed quantifying small bowel motility
      within and upstream of strictures in CD patients using magnetic resonance
      enterography (MRE). METHODS: A total of 91 subjects with stricturing CD (mean age
      36 range 18-88) and undergoing MRE with dynamic motility imaging were identified.
      Of this cohort, 84 subjects were scanned at 1.5 T field strength with the
      remainder at 3 T. Linear regions of interest (ROI) were placed at the stricture,
      immediately upstream of the stricture, and in a proximal normal segment of bowel.
      Maximum bowel calibre (mm) and motility (Arbitrary units) at each ROI were
      calculated using previously validated software. Diameters and motility were
      compared using repeat measures anova and diameter correlated with motility score.
      In 21 subjects with follow-up MRE, ROIs were duplicated and percentage diameter
      and motility change across the two time points correlated. KEY RESULTS: Mean
      diameter within the normal, prestricture and strictured bowel was 20, 30, and 15
      mm (p < 0.001) with motility score 0.43, 0.28, and 0.15 AU, respectively (p <
      0.001). There was a negative correlation between prestricture bowel diameter and
      motility (Pearson's R = -0.47, p < 0.001). For patients with follow-up MRE, there
      was a negative correlation between percentage change in prestricture diameter and
      motility, Spearman's Rho -0.6 p = 0.007. CONCLUSIONS & INFERENCES: Quantified
      small bowel motility during MRE differs significantly between normal,
      prestricture, and strictured bowel. As prestricture bowel dilates, motility
      decreases, although this appears reversible in some.

PMID- 24028649
TI  - Supraglottic airways: the history and current state of prehospital airway
      adjuncts.
AB  - This review discusses the history, developments, benefits, and complications of
      supraglottic devices in prehospital care for adults and pediatrics. Evidence
      supporting their use as well as current controversies and developments in out-of
      hospital cardiac arrest and rapid sequence airway management is discussed.
      Devices reviewed include the Laryngeal Mask Airway, Esophageal Tracheal
      Combitube, Laryngeal Tube, I-Gel, Air-Q, Laryngeal Mask Airway Fastrach, and the
      Supraglottic Airway Laryngopharyngeal Tube (SALT).

PMID- 24028648
TI  - Lead, mercury and cadmium in umbilical cord blood and its association with
      parental epidemiological variables and birth factors.
AB  - BACKGROUND: In Spain, few studies have evaluated prenatal exposure to heavy
      metals. The objective of this study was to describe lead, mercury and cadmium
      concentrations in blood from a sample of newborn-mother-father trios, as well as
      to investigate the association between metals in cord blood and parental
      variables. We also explored the relationship between cord blood metal
      concentrations and child characteristics at birth. METHODS: Metal correlations
      among family members were assessed using Spearman Rank Correlation Coefficient.
      Linear regression was used to explore the association between parental variables
      and log-transformed cord blood lead and cord blood mercury concentrations. In the
      case of cadmium, tobit regression was used due to the existence of samples below
      the detection limit. The association between cord blood metal concentrations and
      child characteristics at birth was evaluated using linear regression. RESULTS:
      Geometric means for lead, mercury and cadmium were 14.09 MUg/L, 6.72 MUg/L and
      0.27 MUg/L in newborns; 19.80 MUg/L, 3.90 MUg/L and 0.53 MUg/L in pregnant women;
      and 33.00 MUg/L, 5.38 MUg/L and 0.49 MUg/L in men. Positive correlations were
      found between metal concentrations among members of the trio. Lead and cadmium
      concentrations were 15% and 22% higher in newborns from mothers who smoked during
      pregnancy, while mercury concentrations were 25% higher in newborns from mothers
      with greater fish intake. Cord-blood lead levels showed seasonal periodicity,
      with lower concentrations observed in winter. Cord blood cadmium concentrations
      over 0.29 MUg/L were associated with lower 1-minute and 5-minute Apgar scores.
      CONCLUSIONS: These results reinforce the need to establish biomonitoring programs
      in Spain, and provide support for tobacco smoke and fish consumption as important
      preventable sources of heavy metal exposure in newborns. Additionally, our
      findings support the hypothesis that cadmium exposure might be deleterious to
      fetal development.

PMID- 24028650
TI  - Food consumption patterns and associated factors among Vietnamese women of
      reproductive age.
AB  - BACKGROUND AND OBJECTIVES: Adequate nutrient intakes among women of reproductive
      age (WRA) are important determinants of maternal, neonatal and child health
      outcomes. However, data on dietary intake for WRA in Vietnam are lacking. This
      paper aimed to examine the adequacy and determinants of energy and macronutrient
      intakes among WRA enrolled in a study of preconceptual micronutrient
      supplementation (PRECONCEPT) being conducted in 20 rural communes in Thai Nguyen
      province, Vietnam. METHODS: Dietary intakes were determined for 4983 WRA who
      participated in the baseline survey using a previously validated 107-item (semi
      quantitative) food-frequency questionnaire that was administered by trained field
      workers. Multivariate linear and logistic regression analyses were used to
      examine factors associated with energy and macronutrient intakes. RESULTS: A
      disproportionate number of energy came from starches, primarily rice.
      Carbohydrate, fat and protein constituted 65.6%, 19.5% and 14.8% of total energy,
      respectively. Fat intake was below recommended levels in 56.5% of respondents,
      but carbohydrate intakes were above recommended level in 54.6%. Only 0.1% and
      5.2% of WRA achieved adequate intake of n-3 and n-6 long-chain polyunsaturated
      fatty acids, respectively. Multivariate linear regression revealed that low
      education, low socioeconomic status, and food insecurity were significant
      predictors of reduced total energy intake, reduced energy from protein and fat,
      and greater energy from carbohydrates. Logistic regression confirmed that
      inadequate macronutrient intake was more common among the poor, food insecure,
      and less educated. CONCLUSIONS: Imbalanced dietary intakes among underprivileged
      women reflect lack of dietary diversity. Nutrition programs should be linked with
      social development, poverty reduction, education programs and behavior change
      counseling in order to improve the nutritional status of WRA in Vietnam.

PMID- 24028652
TI  - Formation of bundle-shaped beta-NaYF4 upconversion microtubes via Ostwald
      ripening.
AB  - In this work, the uniform bundle-shaped microtubes composed of six half-pipes are
      synthesized for the first time in hydrothermal solutions via an intentional
      delayed phase transition pathway induced by Mn(2+) doping. The structural and
      kinetic factors that govern the phase and shape evolution of NaYF4 microcrystals
      have been carefully studied, and the influences of Mn(2+) to RE(3+) ratio, the
      amount of trisodium citrate, and the pH value in conjunction with the intrinsic
      character of RE(3+) ions on the phase and shape evolution are systematically
      discussed. It is found that the proper Mn(2+) to RE(3+) ratio is mainly
      responsible for delayed phase transition process and induces interior density
      gradient of solid aggregate for creating hollow bundle-shaped microtubes. While
      the amount of trisodium citrate and the pH value are the keys for the shape
      control of the NaYF4 microcrystals such as prismatic microtubes, prismatic short
      rods, thin plates, and particles. The up and downconversion emissions were
      obtained independent of whether alpha- or beta-NaYF4:Er(3+)/Yb(3+) samples doped
      with Mn(2+), but the significant tuning of output color was only obtained in cube
      NaYF4 nanoparticles rather than in hexagonal microtubes via adjusting the amount
      of Mn(2+) ions. These spectral measurements and EDX analyses indicate that the
      distribution or concentration of Mn(2+) in hexagonal phase solid solution has
      changed, which supports Ostwald ripening growth mechanism and rules out
      agglomeration or oriented attachment growth mechanism. We designed crystal growth
      mode by simply addition of dopant may provide a versatile approach for
      fabricating a wide range of hollow nano/microcrystals and thus bring us a clearer
      understanding on the interaction between the dopant reagents and the
      nano/microcrystals. 

PMID- 24028651
TI  - Induced expression and functional effects of aquaporin-1 in human leukocytes in
      sepsis.
AB  - INTRODUCTION: Gene expression profiling was performed via DNA microarrays in
      leukocytes from critically ill trauma patients nonseptic upon admission to the
      ICU, who subsequently developed either sepsis (n = 2) or severe sepsis and acute
      respiratory distress syndrome (n = 3). By comparing our results with published
      expression profiling studies in animal models of sepsis and lung injury, we found
      aquaporin-1 to be differentially expressed across all studies. Our aim was to
      determine how the water channel aquaporin-1 is involved in regulating the immune
      response in critically ill patients during infection acquired in the ICU.
      METHODS: Following the results of the initial genetic screening study, we
      prospectively followed aquaporin-1 leukocyte expression patterns in patients with
      ICU-acquired sepsis who subsequently developed septic shock (n = 16) versus
      critically ill patients who were discharged without developing sepsis (n = 13).
      We additionally determined aquaporin-1 expression upon lipopolysaccharide (LPS)
      exposure and explored functional effects of aquaporin-1 induction in
      polymorphonuclear granulocytes (PMNs). RESULTS: Leukocyte aquaporin-1 expression
      was induced at the onset of sepsis (median 1.71-fold increase; interquartile
      range: 0.99 to 2.42, P = 0.012 from baseline) and was further increased upon
      septic shock (median 3.00-fold increase; interquartile range: 1.20 to 5.40, P =
      0.023 from sepsis, Wilcoxon signed-rank test); no difference was observed between
      baseline and discharge in patients who did not develop sepsis. Stimulation of
      PMNs by LPS led to increased expression of aquaporin-1 in vitro, which could be
      abrogated by the NF-kappaB inhibitor EF-24. PMN hypotonic challenge resulted in a
      transient increase of the relative cell volume, which returned to baseline after
      600 seconds, while incubation in the presence of LPS resulted in persistently
      increased cell volume. The latter could be abolished by blocking aquaporin-1 with
      mercury and restored by incubation in beta-mercaptoethanol, which abrogated the
      action of mercury inhibition. CONCLUSIONS: Aquaporin-1 is induced in leukocytes
      of patients with ICU-acquired sepsis and exhibits higher expression in septic
      shock. This phenomenon may be due to LPS-triggered NF-kappaB activation that can
      also lead to alterations in plasma membrane permeability.

PMID- 24028653
TI  - Endogenous endophthalmitis caused by Enterococcus faecalis in a cat.
AB  - A three-year-old male neutered domestic shorthair cat was presented for loss of
      vision associated with hyperthermia, lethargy and anorexia. Ophthalmic
      examination revealed a bilateral panuveitis. Cytological examination of aqueous
      and vitreous humours was performed and revealed a suppurative inflammation
      associated with numerous cocci. Enterococcus faecalis was identified by bacterial
      culture from aqueous and vitreous humour. No primary infection site was
      identified. Active uveitis resolved after systemic antibiotic therapy, but the
      vision loss was permanent. To the authors' knowledge, this is the first reported
      case of endogenous bacterial endophthalmitis secondary to E. faecalis infection
      in a cat.

PMID- 24028655
TI  - Nanocrystal diffusion doping.
AB  - A diffusion-based synthesis of doped colloidal semiconductor nanocrystals is
      demonstrated. This approach involves thermodynamically controlled addition of
      both impurity cations and host anions to preformed seed nanocrystals under
      equilibrium conditions, rather than kinetically controlled doping during growth.
      This chemistry allows thermodynamic crystal compositions to be prepared without
      sacrificing other kinetically trapped properties such as shape, size, or
      crystallographic phase. This doping chemistry thus shares some similarities with
      cation-exchange reactions, but proceeds without the loss of host cations and
      excels at the introduction of relatively unreactive impurity ions that have not
      been previously accessible using cation exchange. Specifically, we demonstrate
      the preparation of Cd(1-x)Mn(x)Se (0 <= x <= ~0.2) nanocrystals with narrow size
      distribution, unprecedentedly high Mn(2+) content, and very large magneto-optical
      effects by diffusion of Mn(2+) into seed CdSe nanocrystals grown by hot
      injection. Controlling the solution and lattice chemical potentials of Cd(2+) and
      Mn(2+) allows Mn(2+) diffusion into the internal volumes of the CdSe nanocrystals
      with negligible Ostwald ripening, while retaining the crystallographic phase
      (wurtzite or zinc blende), shape anisotropy, and ensemble size uniformity of the
      seed nanocrystals. Experimental results for diffusion doping of other
      nanocrystals with other cations are also presented that indicate this method may
      be generalized, providing access to a variety of new doped semiconductor
      nanostructures not previously attainable by kinetic routes or cation exchange.

PMID- 24028654
TI  - Triterpenoid resinous metabolites from the genus Boswellia: pharmacological
      activities and potential species-identifying properties.
AB  - The resinous metabolites commonly known as frankincense or olibanum are produced
      by trees of the genus Boswellia and have attracted increasing popularity in
      Western countries in the last decade for their various pharmacological
      activities. This review described the pharmacological specific details mainly on
      anti-inflammatory, anti-carcinogenic, anti-bacterial and apoptosis-regulating
      activities of individual triterpenoid together with the relevant mechanism. In
      addition, species-characterizing triterpenic markers with the methods for their
      detection, bioavailability, safety and other significant properties were reviewed
      for further research. 

PMID- 24028657
TI  - Outcomes of inpatient mobilization: a literature review.
AB  - AIMS AND OBJECTIVES: To review current research evidence on the outcomes of
      mobilising hospitalised adults. BACKGROUND: Although immobility is known to cause
      functional decline or complications, inpatient ambulation emerged as the most
      often missed element of nursing care. This study is designed to review research
      studies that give evidence as to the consequences of mobilising or not mobilising
      hospitalised adult patients. DESIGN: A literature review of published peer
      reviewed empirical research was undertaken. METHODS: The electronic databases of
      MEDLINE (Ovid), CINAHL, and PubMed were accessed to search for relevant empirical
      articles, supplemented by a search of reference lists contained in retrieved
      articles and citation tracking. RESULTS: Thirty-six studies were identified for
      inclusion in the review. Four areas (study design, sample size, measurement and
      statistical analysis) were evaluated for methodological quality, and most studies
      showed strong quality. A synthesis of the findings generated four themes of the
      effects of inpatient mobilisation: (1) physical outcomes included pain, deep vein
      thrombosis, fatigue, etc.; (2) psychological outcomes included anxiety,
      depressive mood, distress, comfort and satisfaction; (3) social outcomes included
      quality of life and independence; and (4) organisational outcomes included length
      of stay, mortality and cost. CONCLUSION: Mobilising hospitalised adults brings
      benefits for not only physical functioning, but also their emotional and social
      well-being. Moreover, ambulation yields important organisational benefits. These
      benefits of mobilisation on four areas required viewing the patient in a holistic
      manner. Even though each study approached different types of patients, illnesses
      and procedures, this review showed that most inpatients would benefit from
      mobilisation and would experience optimal functions. RELEVANCE TO CLINICAL
      PRACTICE: The importance of mobilisation for positive patient outcomes highlights
      the need to develop methods to ensure that this nursing action is completed on a
      systematic basis.

PMID- 24028656
TI  - Mesenchymal stem cells control alloreactive CD8(+) CD28(-) T cells.
AB  - CD28/B7 co-stimulation blockade with belatacept prevents alloreactivity in kidney
      transplant patients. However, cells lacking CD28 are not susceptible to
      belatacept treatment. As CD8(+) CD28(-) T-cells have cytotoxic and pathogenic
      properties, we investigated whether mesenchymal stem cells (MSC) are effective in
      controlling these cells. In mixed lymphocyte reactions (MLR), MSC and belatacept
      inhibited peripheral blood mononuclear cell (PBMC) proliferation in a dose
      dependent manner. MSC at MSC/effector cell ratios of 1:160 and 1:2.5 reduced
      proliferation by 38.8 and 92.2%, respectively. Belatacept concentrations of 0.1
      MUg/ml and 10 MUg/ml suppressed proliferation by 20.7 and 80.6%, respectively.
      Both treatments in combination did not inhibit each other's function.
      Allostimulated CD8(+) CD28(-) T cells were able to proliferate and expressed the
      cytolytic and cytotoxic effector molecules granzyme B, interferon (IFN)-gamma and
      tumour necrosis factor (TNF)-alpha. While belatacept did not affect the
      proliferation of CD8(+) CD28(-) T cells, MSC reduced the percentage of CD28(-) T
      cells in the proliferating CD8(+) T cell fraction by 45.9% (P = 0.009). CD8(+)
      CD28(-) T cells as effector cells in MLR in the presence of CD4(+) T cell help
      gained CD28 expression, an effect independent of MSC. In contrast, allostimulated
      CD28(+) T cells did not lose CD28 expression in MLR-MSC co-culture, suggesting
      that MSC control pre-existing CD28(-) T cells and not newly induced CD28(-) T
      cells. In conclusion, alloreactive CD8(+) CD28(-) T cells that remain unaffected
      by belatacept treatment are inhibited by MSC. This study indicates the potential
      of an MSC-belatacept combination therapy to control alloreactivity. 

PMID- 24028658
TI  - Reactive oxygen species production induced by ethanol in Saccharomyces cerevisiae
      increases because of a dysfunctional mitochondrial iron-sulfur cluster assembly
      system.
AB  - Ethanol accumulation during fermentation contributes to the toxic effects in
      Saccharomyces cerevisiae, impairing its viability and fermentative capabilities.
      The iron-sulfur (Fe-S) cluster biogenesis is encoded by the ISC genes. Reactive
      oxygen species (ROS) generation is associated with iron release from Fe-S
      containing enzymes. We evaluated ethanol toxicity, ROS generation, antioxidant
      response and mitochondrial integrity in S. cerevisiae ISC mutants. These mutants
      showed an impaired tolerance to ethanol. ROS generation increased substantially
      when ethanol accumulated at toxic concentrations under the fermentation process.
      At the cellular and mitochondrial levels, ROS were increased in yeast treated
      with ethanol and increased to a higher level in the ssq1?, isa1?, iba57? and
      grx5? mutants - hydrogen peroxide and superoxide were the main molecules
      detected. Additionally, ethanol treatment decreased GSH/GSSG ratio and increased
      catalase activity in the ISC mutants. Examination of cytochrome c integrity
      indicated that mitochondrial apoptosis was triggered following ethanol treatment.
      The findings indicate that the mechanism of ethanol toxicity occurs via ROS
      generation dependent on ISC assembly system functionality. In addition, mutations
      in the ISC genes in S. cerevisiae contribute to the increase in ROS concentration
      at the mitochondrial and cellular level, leading to depletion of the antioxidant
      responses and finally to mitochondrial apoptosis.

PMID- 24028659
TI  - A comparison of the electromechanical properties of structurally diverse proteins
      by molecular dynamics simulation.
AB  - Proteins are subjected to electric fields both within the cell and during routine
      biochemical analysis. We have used atomistic molecular dynamics simulations to
      study conformational changes within three structurally diverse proteins subjected
      to high electric fields. At electric fields in excess of .5 V/nm, major
      structural changes were observed in all three proteins due to charge
      redistribution within the biomolecule. However, the electromechanical resilience
      was found to be highly dependent on the protein secondary structure, with alpha
      helices showing a particularly high susceptibility to deformation by the applied
      electric field. 

PMID- 24028660
TI  - Genomic prediction of trait segregation in a progeny population: a case study of
      Japanese pear (Pyrus pyrifolia).
AB  - BACKGROUND: In cross breeding, it is important to choose a good parental
      combination that has high probability of generating offspring with desired
      characteristics. This study examines a method for predicting the segregation of
      target traits in a progeny population based on genome-wide markers and phenotype
      data of parental cultivars. RESULTS: The proposed method combines segregation
      simulation and Bayesian modeling for genomic selection. Marker segregation in a
      progeny population was simulated based on parental genotypes. Posterior marker
      effects sampled via Markov Chain Monte Carlo were used to predict the segregation
      pattern of target traits. The posterior distribution of the proportion of
      progenies that fulfill selection criteria was calculated and used for determining
      a promising cross and the necessary size of the progeny population. We applied
      the proposed method to Japanese pear (Pyrus pyrifolia Nakai) data to demonstrate
      the method and to show how it works in the selection of a promising cross.
      Verification using an actual breeding population suggests that the segregation of
      target traits can be predicted with reasonable accuracy, especially in a highly
      heritable trait. The uncertainty in predictions was reflected on the posterior
      distribution of the proportion of progenies that fulfill selection criteria. A
      simulation study based on the real marker data of Japanese pear cultivars also
      suggests the potential of the method. CONCLUSIONS: The proposed method is useful
      to provide objective and quantitative criteria for choosing a parental
      combination and the breeding population size.

PMID- 24028661
TI  - Comparative outcomes of transvenous extraction of sprint fidelis and riata
      defibrillator leads: a single center experience.
AB  - INTRODUCTION: The FDA has issued class I advisories for Medtronic Sprint
      Fidelis((r)) and St. Jude Medical Riata(TM) ICD lead families. Transvenous
      Riata(TM) ICD lead extraction is typically considered higher risk than
      Fidelis((r)) extraction, based on longer duration from implant, presence of
      externalized conductors and lack of silicone backfill in the SVC and RV coils.
      However, published data comparing procedural outcomes between these leads are
      limited. METHODS: Records were reviewed for all patients undergoing transvenous
      extraction of Sprint Fidelis((r)) or Riata(TM) ICD leads at the Vanderbilt Heart
      and Vascular Institute from July 2006 to April 2013 to ascertain indication for
      extraction, procedural details, complications, and 30-day mortality. RESULTS:
      There were significant differences between those undergoing extraction of a
      Sprint Fidelis((r)) (n = 145) or Riata(TM) lead (n = 47). In the Riata(TM) group,
      device-related endocarditis was a more common indication for extraction, the mean
      duration of implant was longer, and larger excimer laser sheaths were required.
      Lead malfunction was a more common indication in the Fidelis((r)) group. There
      were no statistically significant differences in median procedure duration,
      procedural success (97.9% vs 95.7%, P = 0.41), median length of hospital stay (1
      day vs 1 day, P = 0.23), procedural complication rate (5.5% vs 10.6%, P = 0.23)
      or 30-day mortality (2.1% vs 2.1%, P = 0.98). Analyses excluding patients with
      device infection revealed similar results. CONCLUSION: Despite differences in
      baseline characteristics, this study indicates that Medtronic Sprint Fidelis((r))
      and St. Jude Riata(TM) ICD leads have similar procedural outcomes with
      transvenous lead extraction.

PMID- 24028662
TI  - Characterization of odor-active compounds in sweet-type Chinese rice wine by
      aroma extract dilution analysis with special emphasis on sotolon.
AB  - The aroma characteristics of sweet-type Chinese rice wine were studied by sensory
      analysis, aroma extract dilution analysis (AEDA), and quantitative analysis.
      Sensory evaluation demonstrated that a caramel-like note was the most distinctive
      characteristic for sweet-type Chinese rice wine. AEDA was carried out on the
      extract of a typical sweet-type Chinese rice wine sample. Thirty-nine odor-active
      regions were detected in the sample with a flavor dilution (FD) factor >=8, and
      37 of these were further identified. Among them, sotolon and 2- and 3
      methylbutanol showed the highest FD factor of 1024, followed by 2-acetyl-1
      pyrroline (tentatively identified), dimethyl trisulfide, 2-phenylethanol, and
      vanillin with a FD factor of 512. Sotolon was identified as a key aroma compound
      in Chinese rice wine for the first time. AEDA results indicated that sotolon
      (caramel-like/seasoning-like) was the potentially key contributor to the caramel
      like descriptor of sweet-type Chinese rice wine. The concentration of sotolon in
      Chinese rice wine was further quantitated by Lichrolut-EN solid-phase extraction
      coupled with microvial insert large volume injection method. The content of
      sotolon ranged from 35.93 to 526.17 MUg/L, which was above its odor threshold (9
      MUg/L) for all Chinese rice wine samples. The highest concentration of sotolon
      was found in the sweet-type Chinese rice wine, which highlighted the important
      aroma role of sotolon for this particular type of Chinese rice wine. 

PMID- 24028663
TI  - Bioavailability and immunotoxicity of silver nanoparticles to the freshwater
      mussel Elliptio complanata.
AB  - The purpose of this study was to examine the effects of Ag nanoparticles (nAg) of
      two different sizes (20 and 80 nm) and Ag(+) on the immune system of the
      freshwater mussel Elliptio complanata. Mussels were exposed to increasing
      concentrations of nAg and dissolved Ag (AgNO3) for 48 h at 15 degrees C and
      concentration of 0, 0.8, 4, or 20 MUg/L. Immunocompetence was determined by
      hemocyte viability, phagocytosis, and cell cytotoxicity. Ag tissue loadings and
      levels of metallothioneins (MT), lipid peroxidation (LPO), and labile zinc (Zn)
      were also determined. Results revealed first that 20- and 80-nm nAg readily
      formed aggregates in freshwater. Ag was detected in soft tissues with each form
      of Ag with bioconcentration factors of 20, 9, and 7 for Ag(+), 20-nm nAg, and 80
      nm nAg, respectively. Significant induction in phagocytosis and decreased cell
      cytotoxicity were observed. All forms of Ag were able to induce LPO in gills and
      digestive glands at concentrations below those from the initial fraction of
      dissolved Ag. The effects of nAg on MT levels in mussels were not discernible
      from those of dissolved Ag, but the 80-nm was 25-fold more potent than 20-nm nAg
      in inducing MT. Multivariate analysis revealed that the global responses of the
      20- and 80-nm nAg were generally similar to those of dissolved Ag. Data also
      demonstrated that nAg are bioavailable for mussels where the immune system is a
      target during early exposure to nanoparticles. 

PMID- 24028664
TI  - Jet fuel kerosene is not immunosuppressive in mice or rats following inhalation
      for 28 days.
AB  - Previous reports indicated that inhalation of JP-8 aviation turbine fuel is
      immunosuppressive. However, in some of those studies, the exposure concentrations
      were underestimated, and percent of test article as vapor or aerosol was not
      determined. Furthermore, it is unknown whether the observed effects are
      attributable to the base hydrocarbon fuel (jet fuel kerosene) or to the various
      fuel additives in jet fuels. The present studies were conducted, in compliance
      with Good Laboratory Practice (GLP) regulations, to evaluate the effects of jet
      fuel kerosene on the immune system, in conjunction with an accurate, quantitative
      characterization of the aerosol and vapor exposure concentrations. Two female
      rodent species (B6C3F1 mice and Crl:CD rats) were exposed by nose-only inhalation
      to jet fuel kerosene at targeted concentrations of 0, 500, 1000, or 2000 mg/m(3)
      for 6 h daily for 28 d. Humoral, cell-mediated, and innate immune functions were
      subsequently evaluated. No marked effects were observed in either species on body
      weights, spleen or thymus weights, the T-dependent antibody-forming cell response
      (plaque assay), or the delayed-type hypersensitivity (DTH) response. With a few
      exceptions, spleen cell numbers and phenotypes were also unaffected. Natural
      killer (NK) cell activity in mice was unaffected, while the NK assessment in rats
      was not usable due to an unusually low response in all groups. These studies
      demonstrate that inhalation of jet fuel kerosene for 28 d at levels up to 2000
      mg/m(3) did not adversely affect the functional immune responses of female mice
      and rats. 

PMID- 24028665
TI  - Agricultural exposures and stroke mortality in the Agricultural Health Study.
AB  - Exposures associated with common agricultural activities may increase risk of
      stroke. The authors evaluated associations between self-reported agricultural
      activities including pesticide use and handling of crops and stroke mortality
      among 51,603 male pesticide applicators enrolled in the Agricultural Health Study
      (AHS). Vital status was obtained through 2008. Stroke mortality was defined by
      underlying or contributing cause of death (ICD-9 430-438, ICD-10 I60-I69).
      Information regarding lifetime pesticide use, working with crops or animals,
      engagement in other agricultural activities, and potential confounders was self
      reported at enrollment. Cox proportional hazards models, with age as the time
      scale, were used to estimate hazard ratios (HR) and 95% confidence intervals (CI)
      adjusted for state of residence, smoking status, and alcohol consumption. Median
      follow-up time was 13 yr, during which 308 stroke deaths occurred. No measure of
      overall or specific pesticide use was positively associated with mortality due to
      stroke. Stroke mortality was inversely associated with handling hay, grain, or
      silage at least once each year as reported at enrollment (HR: 0.75; 95% CI: 0.58,
      0.98). There was no evidence of an association between pesticide use and stroke
      mortality. The inverse association between handling of hays and grains and stroke
      mortality may be due to (1) those engaging in such activities being healthier
      than those who did not or (2) exposure to some biological agent present in hays
      and grains. Further investigation of incident stroke, rather than stroke
      mortality, as well as stroke subtypes, is needed to determine the full role of
      agricultural exposures and stroke. 

PMID- 24028666
TI  - Mouse assay for determination of arsenic bioavailability in contaminated soils.
AB  - A mouse assay for measuring the relative bioavailability (RBA) of arsenic (As) in
      soil was developed. In this study, results are presented of RBA assays of 16
      soils, including multiple assays of the same soils, which provide a quantitative
      assessment of reproducibility of mouse assay results, as well as a comparison of
      results from the mouse assay with results from a swine and monkey assay applied
      to the same test soils. The mouse assay is highly reproducible; three repeated
      assays on the same soils yielded RBA estimates that ranged from 1 to 3% of the
      group mean. The mouse, monkey, and swine models yielded similar results for some,
      but not all, test materials. RBA estimates for identical soils (nine test soils
      and three standard reference materials [SRM]) assayed in mice and swine were
      significantly correlated (r = 0.70). Swine RBA estimates for 6 of the 12 test
      materials were higher than those from the mouse assay. RBA estimates for three
      standard reference materials (SRM) were not statistically different (mouse/swine
      ratio ranged from 0.86-1). When four test soils from the same orchard were
      assessed in the mouse, monkey, and swine assays, the mean soil As RBA were not
      statistically different. Mouse and swine models predicted similar steady state
      urinary excretion fractions (UEF) for As of 62 and 74%, respectively, during
      repeated ingestion doses of sodium arsenate, the water-soluble As form used as
      the reference in the calculation of RBA. In the mouse assay, the UEF for water
      soluble As(V) (sodium arsenate) and As(III) (sodium [meta] arsenite) were 62% and
      66%, respectively, suggesting similar absolute bioavailabilities for the two As
      species. The mouse assay can serve as a highly cost-effective alternative or
      supplement to monkey and swine assays for improving As risk assessments by
      providing site-specific assessments of RBA of As in soils.

PMID- 24028667
TI  - Effects of COREXIT dispersants on cytotoxicity parameters in a cultured human
      bronchial airway cells, BEAS-2B.
AB  - The objective of this study was to assess the cytotoxicity of COREXIT dispersants
      EC9500A, EC9527A, and EC9580A on human airway BEAS-2B epithelial cells. Cells
      were exposed to dispersants for 2 or 24 h at concentrations ranging from 0 to 300
      ppm. COREXIT EC9527 at 100 ppm produced 50% viability loss as measured by 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) at 24 h. COREXIT 9527
      at 200 ppm produced 50% cell death at 2 h and 100% at 24 h. At 300 ppm COREXIT
      9527 induced 100% cell death at 2 or 24 h. In the case of COREXIT 9500A 50% cell
      viability was noted with 200 ppm at 2 or 24 h, with a significant decrease in
      cell survival to 2% at 300 ppm. In contrast, no marked change in cell viability
      was observed in cells treated at any COREXIT 9580A concentration examined.
      Western blot analysis showed an increase in expression of LC3B, a marker of
      autophagy, in cells treated for 2 h with 300 ppm COREXIT EC9527A as well as 100
      or 300 ppm Corexit EC9500A. No marked effect on LC3B expression was observed for
      any COREXIT 9580A concentration. Apoptosis markers as measured by cleaved caspase
      3 and cleaved poly(ADP-ribose) polymerase (PARP) were detectable only in cells
      incubated with 300 ppm COREXIT EC9527A. Although all three dispersants induced
      enhanced generation of reactive oxygen species (ROS) after 2-h treatment at 300
      ppm, Western blot analysis revealed that 2-h incubation was not sufficient to
      induce a significant change in the protein expression of superoxide dismutases
      SOD1, SOD2, and SOD3. Data thus indicate exposure to certain dispersants may be
      harmful to human airway epithelial cells in a concentration-dependent manner. 

PMID- 24028668
TI  - Adiposity among children in Norway by urbanity and maternal education: a
      nationally representative study.
AB  - BACKGROUND: International research has demonstrated that rural residency is a
      risk factor for childhood adiposity. The main aim of this study was to
      investigate the urban-rural gradient in overweight and obesity and whether the
      association differed by maternal education. METHODS: Height, weight and waist
      circumference (WC) were measured in a nationally representative sample of 3166
      Norwegian eight-year-olds in 2010. Anthropometric measures were stratified by
      area of residence (urbanity) and maternal education. Risk estimates for
      overweight (including obesity) and waist-to-height ratio >=0.5 were calculated by
      log-binomial regression. RESULTS: Mean BMI and WC and risk estimates of
      overweight (including obesity) and waist-to-height ratio >=0.5 were associated
      with both urbanity and maternal education. These associations were robust after
      mutual adjustment for each other. Furthermore, there was an indication of
      interaction between urbanity and maternal education, as trends of mean BMI and WC
      increased from urban to rural residence among children of low-educated mothers (p
      = 0.01 for both BMI and WC), whereas corresponding trends for children from
      higher educational background were non-significant (p > 0.30). However, formal
      tests of the interaction term urbanity by maternal education were non-significant
      (p-value for interaction was 0.29 for BMI and 0.31 for WC). CONCLUSIONS: In this
      nationally representative study, children living rurally and children of low
      educated mothers had higher mean BMI and waist circumference than children living
      in more urban areas and children of higher educated mothers.

PMID- 24028669
TI  - More satisfied, but why? A pooled patient-level analysis of treatment
      satisfaction following the initiation of insulin glargine vs. comparators in
      insulin-naive patients with type 2 diabetes mellitus.
AB  - AIM: To assess patient-reported outcomes associated with initiating insulin
      glargine among insulin-naive patients with type 2 diabetes mellitus (T2DM).
      METHODS: This was a pooled analysis of patient-level data from Phase 3,
      randomized controlled trials evaluating once-daily insulin glargine vs.
      comparator treatment for >=24 weeks in previously insulin-naive adult patients
      with T2DM and poor glycaemic control. Eligible studies utilized strict,
      predefined insulin titration algorithms with weekly dose-adjustment to achieve
      fasting plasma glucose (FPG) levels of <=5.6 mmol/l. Treatment satisfaction was
      measured using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) change
      (c) and status (s) versions. RESULTS: A total of 1577 patients from four studies
      were included; 830 patients treated with insulin glargine and 747 with
      comparators. At week 24, DTSQc scores improved in both groups with a
      significantly higher increase in treatment satisfaction for insulin glargine vs.
      comparators (13.5 vs. 12.1; p < 0.0001). Multivariate regression analysis
      revealed that significant predictors of DTSQc improvement at week 24 were insulin
      glargine treatment (p < 0.0001), higher baseline DTSQs (p < 0.0001), and lower
      baseline body weight (p = 0.0103). Greater improvement in DTSQc at week 24 was
      significantly associated with decrease from baseline in glycosylated haemoglobin
      (p < 0.001) and FPG (p = 0.0001); a numerically more positive change in weight
      from baseline approached significance (p = 0.07). CONCLUSION: Initiation of
      insulin glargine in insulin-naive patients with T2DM is associated with greater
      improvements in treatment satisfaction than alternative interventions, with
      perceived improvements in glycaemic control and baseline weight likely to be
      important factors.

PMID- 24028670
TI  - Effects of formulating growing pig diet with increasing levels of wheat-corn
      distillers dried grains with solubles on digestible nutrient basis on growth
      performance and nutrient digestibility.
AB  - Formulating swine diets containing fibrous coproducts based on net energy (NE)
      and standardized ileal digestible amino acid (SID AA) values is recommended for
      optimizing pig performance. However, the effects of applying this approach to
      diets with increasing dietary levels of wheat-corn-derived distillers dried
      grains with soluble (wcDDGS) on pig performance have not been evaluated. Thus, 48
      pigs with an average body weight [BW] of 25.5 kg were used to determine the
      effects of increasing wcDDGS (1:1 wheat to corn ratio) content in grower diets on
      performance and apparent total tract digestibility (ATTD) of energy and
      nutrients. Pigs were housed in pens of either 2 barrows or gilts balanced for BW
      and fed 4 diets within sex for 42 days. Diets were a nutrient adequate corn
      barley-soybean meal-based diet with 0%, 10%, 20% and 30% wcDDGS, and were similar
      in calculated NE and SID AA values. Acid insoluble ash was used as the
      indigestible marker. Final BW and overall average daily gain (ADG) linearly
      decreased (p < 0.05) and feed efficiency tended to decrease (p = 0.07) with
      increased dietary wcDDGS. Overall average daily feed intake was not affected (p >
      0.10) by dietary treatment. The ATTD of dry matter and energy linearly decreased
      (p < 0.01), whereas the ATTD of neutral detergent fibre linearly increased (p <
      0.01) with increasing dietary level of wcDDGS. Increasing dietary wcDDGS content
      did not affect (p > 0.10) ATTD of Ca and P. In conclusion, increasing dietary
      wcDDGS content reduced growth performance and ATTD of energy in growing pigs.
      Thus, the risks of high dietary wcDGGS content may not be completely alleviated
      by formulating growing pig diets on the basis of NE and SID AA systems. 

PMID- 24028671
TI  - Milk cereal drink increases BMI risk at 12 and 18 months, but formula does not.
AB  - AIM: Infant feeding affects growth, obesity and life-long health. This study
      examined the impact of dietary patterns on body mass index (BMI) at 12 and 18
      months. METHODS: We followed a cohort of 2666 children recruited in 2007-2008.
      Feeding practices were obtained from parental questionnaires and anthropometric
      data collected by child health nurses. RESULTS: At 6 months, 58.3% of the infant
      were breastfed, but only 1.6% exclusively. Many had begun eating solids (91.8%),
      porridge (87.7%) or milk cereal drink (46.6%). Bottle-feeding at 4 months was not
      a risk factor for a high BMI (>1 SD) at 12 or 18 months. Milk cereal drink at six
      months increased the risk of a high BMI at 12 and 18 months, respectively (OR
      1.58, 95% CI 1.12-2.22, and 1.52, 1.07-2.17). Milk cereal drink use was increased
      by low parental education and maternal obesity and reduced by troubled sleep and
      parental group participation. CONCLUSION: Formula at 4 months did not predict a
      high BMI at 12 or 18 months. Milk cereal drink use at 6 months was a risk factor
      for a high BMI at 12 and 18 months. The choice of milk cereal drink was
      influenced by parental factors, especially educational levels.

PMID- 24028672
TI  - Isolation of tumor antigen-specific single-chain variable fragments using a
      chimeric antigen receptor bicistronic retroviral vector in a Mammalian screening
      protocol.
AB  - The clinical potential of chimeric antigen receptors in adoptive cellular therapy
      is beginning to be realized with several recent clinical trials targeting CD19
      showing promising results in advanced B cell malignancies. This increased
      efficacy corresponds with improved engineering of the chimeric receptors with the
      latest-generation receptors eliciting greater signaling and proliferation
      potential. However, the antigen-binding single-chain variable fragment (scFv)
      domain of the receptors is critical in determining the activity of the chimeric
      receptor-expressing T cells, as this determines specificity and affinity to the
      tumor antigen. In this study, we describe a mammalian T cell line screening
      protocol employing a 2A-based bicistronic retroviral vector to isolate functional
      scFvs. This approach involves expression of the scFv library in a chimeric
      antigen receptor, and is based on selection of clones capable of stimulating CD69
      upregulation in a T cell line and has a number of advantages over previously
      described methods in that the use of a 2A cassette ensures the exclusion of
      nonexpressing scFvs and the screening using a chimeric receptor in a mammalian T
      cell line ensures selection in the optimum context for therapeutic use. Proof-of
      principle experiments show that the protocol was capable of a 10(5)-fold
      enrichment of positive clones after three rounds of selection. Furthermore, an
      antigen-specific clone was successfully isolated from a partially enriched scFv
      library, confirming the strength of the protocol. This approach has the potential
      to identify novel scFvs of use in adoptive T cell therapy and, potentially, wider
      antibody-based applications.

PMID- 24028674
TI  - Organocatalytic C-H/C-H' cross-biaryl coupling: C-selective arylation of
      sulfonanilides with aromatic hydrocarbons.
AB  - The hypervalent iodine-mediated C-C selective coupling of N-methanesulfonyl
      anilides with aromatic hydrocarbons has been developed. The first organocatalytic
      oxidative cross-biaryl-coupling was achieved by the catalyst control in defining
      specific 2,2'-diiodobiphenyls for the direct C-C bond formations. 

PMID- 24028675
TI  - Does decreased mean platelet volume predict inflammation in chronic renal
      failure, dialysis, and transplanted patients?
AB  - OBJECTIVES: Increased platelet activation contributes to cardiovascular mortality
      in chronic kidney disease patients (CKD). Larger platelets are more active and
      this increased activity had been suggested as a predictive biomarker for
      cardiovascular disease. In this study, we aimed to evaluate mean platelet volume
      (MPV) as an inflammatory marker in a broadened group of CKD patients. Our study
      is unique in literature as it covers all types of CKD including renal replacement
      therapies. MATERIALS AND METHODS: 200 patients (50 renal transplanted, 50
      hemodialysis, 50 peritoneal dialysis, 50 chronic renal failure stages 3-4) were
      investigated who were between 18 and 76 years of age. The collected data included
      demographic properties, platelet count, MPV, C-reactive protein (CRP),
      erythrocyte sedimentation rate (ESR), and hemoglobin. All of the patients had at
      least 12 month of therapy of either renal replacement modality. RESULTS: The mean
      CRP value was detected statistically significantly higher in hemodialysis (HD)
      patients compared to the resting three groups of patients (p < 0.01). Mean CRP
      level was detected significantly higher in the pre-dialysis group compared to
      transplanted and peritoneal dialysis (PD) patients (p < 0.01). There is no
      statistically significant difference detected among the mean MPV values of all
      patient groups (p > 0.05). CONCLUSIONS: ESR and CRP were significantly increased
      in hemodialysis patients compared to the other groups. We did not detect a
      significant difference among MPV between the groups. ESR was detected lowest in
      transplanted patients. Transplantation is coming forward as the favorable choice
      of renal replacement therapy which decreases inflammation.

PMID- 24028676
TI  - Magnetic properties of single crystalline expanded austenite obtained by plasma
      nitriding of austenitic stainless steel single crystals.
AB  - Ferromagnetic single crystalline [100], [110], and [111]-oriented expanded
      austenite is obtained by plasma nitriding of paramagnetic 316L austenitic
      stainless steel single crystals at either 300 or 400  degrees C. After nitriding
      at 400  degrees C, the [100] direction appears to constitute the magnetic easy
      axis due to the interplay between a large lattice expansion and the expected
      decomposition of the expanded austenite, which results in Fe- and Ni-enriched
      areas. However, a complex combination of uniaxial (i.e., twofold) and biaxial
      (i.e., fourfold) in-plane magnetic anisotropies is encountered. It is suggested
      that the former is related to residual stress-induced effects while the latter is
      associated to the in-plane projections of the cubic lattice symmetry. Increasing
      the processing temperature strengthens the biaxial in-plane anisotropy in
      detriment of the uniaxial contribution, in agreement with a more homogeneous
      structure of expanded austenite with lower residual stresses. In contrast to
      polycrystalline expanded austenite, single crystalline expanded austenite
      exhibits its magnetic easy axes along basic directions. 

PMID- 24028677
TI  - Immunogenicity and safety of omalizumab in pre-filled syringes in patients with
      allergic (IgE-mediated) asthma.
AB  - BACKGROUND: Omalizumab, a humanised anti-immunoglobulin E monoclonal antibody for
      treatment of uncontrolled moderate-to-severe or severe persistent allergic
      asthma, was developed as a lyophilised powder for reconstitution. A liquid
      formulation in pre-filled syringes has now been developed. The purpose of this
      study was to assess the immunogenicity and safety of this liquid formulation.
      METHODS: In this multinational, open-label, single-arm study, patients (>=12
      years) with moderate-to-severe allergic asthma were treated for 24 weeks with the
      liquid formulation of omalizumab (75 or 150 mg in a pre-filled syringe) at 2 or 4
      week intervals. Immunogenicity was assessed by measurement of human anti
      therapeutic antibody (ATA) levels. Safety was assessed by monitoring adverse
      events (AEs), haematology, blood chemistry, urine analysis and vital signs.
      RESULTS: A total of 155 patients were enrolled in the study. No patient had a
      confirmed positive ATA test result. Most frequent individual AEs were asthma
      (17.4%), sinusitis (17.4%) and upper respiratory tract infection (11.6%).
      Fourteen patients (9.0%) had serious AEs and there was one death (not treatment
      related). There were no cases of anaphylaxis according to Sampson criteria. Most
      patients remained within normal ranges for haematology and biochemistry
      laboratory variables. CONCLUSIONS: Omalizumab in pre-filled syringes was not
      associated with immunogenicity. This novel formulation, which does not require
      reconstitution, had a safety profile consistent with the lyophilised formulation.
      A limitation of this study is that efficacy of omalizumab in the treatment of
      asthma was not specifically addressed herein. Clinicaltrials.gov identifier:
      NCT00500539.

PMID- 24028678
TI  - Treatment of cardiac arrest with rapid defibrillation by police in King County,
      Washington.
AB  - BACKGROUND: Improving survival from out-of-hospital cardiac arrest is an ongoing
      challenge for emergency medical services (EMS). Various strategies for shortening
      the time from collapse to defibrillation have been used, and one is to equip
      police officers with defibrillators. Objective. We evaluated the programmatic
      implementation of police defibrillation to determine if such a program could
      improve the process of care in a high-functioning and mature EMS system. METHODS:
      We conducted a prospective observational study of implementation of a police
      defibrillation in two police departments in King County, Washington, from March
      1, 2010 to March 31, 2012. The program was designed to dispatch police
      specifically to cases with a high suspicion of cardiac arrest, defined as a
      patient who was unconscious and not breathing normally. We included all
      nontraumatic out-of-hospital cardiac arrest events that occurred prior to EMS
      arrival and within the city limits of the two cities. We collected both EMS and
      police dispatch reports to document times of call receipt, dispatch, and arrival
      of both agencies. We obtained rhythm recordings when the automated external
      defibrillators (AEDs) were used by the police. Descriptive statistics were used
      to measure frequency of police dispatch and to compare times to treatment between
      patients with a police response and those without. RESULTS: During the study
      period there were 231 cases of cardiac arrest that occurred prior to EMS arrival
      eligible for police response in the study communities. Police were dispatched to
      124 (54%) of these cases. Of the 124, the police arrived before EMS 37 times, or
      16% of the 231 cases. Police performed CPR in 29 of these cases and applied the
      AED in 21 of them. Of the 21 cases in which the AED was applied for cardiac
      arrest, a shock was delivered on first analysis for 6 patients. Although the
      response interval between dispatch to scene arrival was similar for EMS and
      police (4.5 minutes versus 4.6 minutes respectively, p = 0.08), police were
      dispatched considerably slower than EMS (1.8 minutes versus 0.6 minutes, p <
      0.001). CONCLUSIONS: In the current programmatic implementation, police had a
      measurable but limited involvement in resuscitation. Efforts to address dispatch
      challenges may improve police involvement.

PMID- 24028679
TI  - Congruent species delineation of Tulasnella using multiple loci and methods.

PMID- 24028673
TI  - The diagnostic performance of the Mass Restricted (MR) score in the
      identification of microbial invasion of the amniotic cavity or intra-amniotic
      inflammation is not superior to amniotic fluid interleukin-6.
AB  - OBJECTIVE: Intra-amniotic infection/inflammation are major causes of spontaneous
      preterm labor and delivery. However, diagnosis of intra-amniotic infection is
      challenging because most are subclinical and amniotic fluid (AF) cultures take
      several days before results are available. Several tests have been proposed for
      the rapid diagnosis of microbial invasion of the amniotic cavity (MIAC) or intra
      amniotic inflammation. The aim of this study was to examine the diagnostic
      performance of the AF Mass Restricted (MR) score in comparison with interleukin-6
      (IL-6) and matrix metalloproteinase-8 (MMP-8) for the identification of MIAC or
      inflammation. METHODS: AF samples were collected from patients with singleton
      gestations and symptoms of preterm labor (n = 100). Intra-amniotic inflammation
      was defined as >100 white blood cells/mm(3) (WBCs) in AF; MIAC was defined as a
      positive AF culture. AF IL-6 and MMP-8 were determined using ELISA. The MR score
      was obtained using the Surface-Enhanced Laser Desorption Ionization Time of
      Flight (SELDI-TOF) mass spectrometry. Sensitivity and specificity were calculated
      and logistic regression models were fit to construct receiver-operating
      characteristic (ROC) curves for the identification of each outcome. The McNemar's
      test and paired sample non-parametric statistical techniques were used to test
      for differences in diagnostic performance metrics. RESULTS: (1) The prevalence of
      MIAC and intra-amniotic inflammation was 34% (34/100) and 40% (40/100),
      respectively; (2) there were no significant differences in sensitivity of the
      three tests under study (MR score, IL-6 or MMP-8) in the identification of either
      MIAC or intra-amniotic inflammation (using the following cutoffs: MR score >2, IL
      6 >11.4 ng/mL, and MMP-8 >23 ng/mL); (3) there was no significant difference in
      the sensitivity among the three tests for the same outcomes when the false
      positive rate was fixed at 15%; (4) the specificity for IL-6 was not
      significantly different from that of the MR score in identifying either MIAC or
      intra-amniotic inflammation when using previously reported thresholds; and (5)
      there were no significant differences in the area under the ROC curve when
      comparing the MR score, IL-6 or MMP-8 in the identification of these outcomes.
      CONCLUSIONS: IL-6 and the MR score have equivalent diagnostic performance in the
      identification of MIAC or intra-amniotic inflammation. Selection from among these
      three tests (MR score, IL-6 and MMP-8) for diagnostic purposes should be based on
      factors such as availability, reproducibility, and cost. The MR score requires a
      protein chip and a SELDI-TOF instrument which are not widely available or
      considered "state of the art". In contrast, immunoassays for IL-6 can be
      performed in the majority of clinical laboratories.

PMID- 24028680
TI  - Assessing change in the behavior of children and adolescents in youth welfare
      institutions using goal attainment scaling.
AB  - BACKGROUND: Evaluating youth welfare services is vital, both because of the
      considerable influence they have on the development of children and adolescents,
      as well as owing to the extensive financial costs involved, especially for child
      residential care. In this naturalistic study we have undertaken to evaluate
      changes in various behaviors of young people who are in youth welfare
      institutions, not only by using standardized questionnaires, but also
      specifically modified goal attainment scales (GAS). These scales were meant to
      represent the pedagogical objectives of youth welfare professionals as well as
      the individual goals of the young people in care. METHODS: Goal attainment scales
      were used to ascertain behavioral changes in 433 children and adolescents (age 6
      to 18 years) in 25 youth welfare institutions (day care and residential care) in
      Germany. Social and individual goals were rated by young people and caregivers
      together on at least two occasions. In addition, to examine potential problems of
      children and adolescents, quality of life as well as mental health and behavior
      problems were identified by the caregiver and also by the youth using a self
      report inventory. RESULTS: Many of the children and adolescents had experienced
      critical life events, problems in school, impaired quality of life, along with
      mental health and behavior problems (range: 41-87%). During their stay in day
      care or residential care institutions, children and adolescents showed some
      improvement in social goals (Cohen's d = 0.14-0.44), especially those young
      people with deficits at the beginning, and with regard to mental health and
      problem behavior (d = 0.10-0.31). For individual goals, progress was even more
      pronounced (d = 0.75). Improvements to social goals were more pronounced if
      mental health and behavior problems decreased. This link to changes in behavioral
      and emotional problems was only ascertained to a limited extent for individual
      goals. CONCLUSIONS: Young people residing in youth welfare institutions achieved
      individual and social goals and improved with regard to behavior problems. The
      applied goal attainment scales are well suited for measuring individual change in
      children and adolescents and constitute a relevant addition to established
      instruments. Furthermore, their advantages include cooperative goal setting, the
      assessment of goals by caregivers and young people, and congruence with the
      pedagogical objectives of professionals.

PMID- 24028681
TI  - Paraneoplastic stiff person syndrome associated with colon cancer misdiagnosed as
      idiopathic Parkinson's disease worsened after capecitabine therapy.
AB  - OBJECTIVES: To refresh clinical diagnostic dilemmas in patients presenting with
      symptoms resembling to those of parkinsonism, to report rare association of colon
      cancer and paraneoplastic stiff person syndrome (SPS), and to draw attention on
      the possible correlation of capecitabine therapy with worsening of paraneoplastic
      SPS. METHODS: Case report of the patient with paraneoplastic SPS due to colon
      cancer that was misdiagnosed as idiopathic Parkinson's disease (iPD), whose
      symptoms worsened after beginning adjuvant capecitabine chemotherapy. RESULTS: We
      describe a 55-year-old woman with subacute onset of symmetrical stiffness and
      rigidity of the truncal and proximal lower limb muscles that caused lower body
      bradykinesia, gait difficulties, and postural instability. Diagnose of iPD was
      made and levodopa treatment was initiated but failed to provide beneficial
      effect. Six months later, colon cancer was discovered and the patient underwent
      surgical procedure and chemotherapy with capecitabine thereafter. Aggravation of
      stiffness, rigidity, and low back pain was observed after the first chemotherapy
      cycle and capecitabine was discontinued. Furthermore, levodopa was slowly
      discontinued and low dose of diazepam was administered which resulted in partial
      resolution of the patient's symptoms. CONCLUSION: Paraneoplastic SPS is rare
      disorder with clinical features resembling those of parkinsonian syndrome and
      making the correct diagnosis remains a challenge. The diagnosis of parkinsonian
      syndrome should be re-examined if subsequent examinations discover an associated
      malignant process. Although it remains unclear whether the patients with history
      of SPS are at the greater risk for symptoms deterioration after administration of
      capecitabine, clinicians should be aware of capecitabine side effects because
      recognition and appropriate management can prevent serious adverse outcomes.

PMID- 24028682
TI  - Body temperature patterns as a predictor of hospital-acquired sepsis in afebrile
      adult intensive care unit patients: a case-control study.
AB  - INTRODUCTION: Early treatment of sepsis improves survival, but early diagnosis of
      hospital-acquired sepsis, especially in critically ill patients, is challenging.
      Evidence suggests that subtle changes in body temperature patterns may be an
      early indicator of sepsis, but data is limited. The aim of this study was to
      examine whether abnormal body temperature patterns, as identified by visual
      examination, could predict the subsequent diagnosis of sepsis in afebrile
      critically ill patients. METHODS: Retrospective case-control study of 32 septic
      and 29 non-septic patients in an adult medical and surgical ICU. Temperature
      curves for the period starting 72 hours and ending 8 hours prior to the clinical
      suspicion of sepsis (for septic patients) and for the 72-hour period prior to
      discharge from the ICU (for non-septic patients) were rated as normal or abnormal
      by seven blinded physicians. Multivariable logistic regression was used to
      compare groups in regard to maximum temperature, minimum temperature, greatest
      change in temperature in any 24-hour period, and whether the majority of
      evaluators rated the curve to be abnormal. RESULTS: Baseline characteristics of
      the groups were similar except the septic group had more trauma patients (31.3%
      vs. 6.9%, p = .02) and more patients requiring mechanical ventilation (75.0% vs.
      41.4%, p = .008). Multivariable logistic regression to control for baseline
      differences demonstrated that septic patients had significantly larger
      temperature deviations in any 24-hour period compared to control patients (1.5
      degrees C vs. 1.1 degrees C, p = .02). An abnormal temperature pattern was noted
      by a majority of the evaluators in 22 (68.8%) septic patients and 7 (24.1%)
      control patients (adjusted OR 4.43, p = .017). This resulted in a sensitivity of
      0.69 (95% CI [confidence interval] 0.50, 0.83) and specificity of 0.76 (95% CI
      0.56, 0.89) of abnormal temperature curves to predict sepsis. The median time
      from the temperature plot to the first culture was 9.40 hours (IQR [inter
      quartile range] 8.00, 18.20) and to the first dose of antibiotics was 16.90 hours
      (IQR 8.35, 34.20). CONCLUSIONS: Abnormal body temperature curves were predictive
      of the diagnosis of sepsis in afebrile critically ill patients. Analysis of
      temperature patterns, rather than absolute values, may facilitate decreased time
      to antimicrobial therapy.

PMID- 24028684
TI  - Striving for habitual well-being in noninvasive ventilation: a grounded theory
      study of chronic obstructive pulmonary disease patients with acute respiratory
      failure.
AB  - AIMS AND OBJECTIVES: To present a theoretical account of the pattern of behaviour
      in patients with acute respiratory failure due to chronic obstructive pulmonary
      disease while undergoing noninvasive ventilation in a hospital setting.
      BACKGROUND: Strong evidence supports a positive effect of noninvasive
      ventilation, but successful treatment remains a challenge. Little attention has
      been given to patient intolerance to noninvasive ventilation as a cause of
      treatment failure. A better understanding of the patients' patterns of behaviour
      during noninvasive ventilation may improve treatment success. DESIGN: A constant
      comparative classic grounded theory study was performed. METHODS: Data collection
      consisted of participant observation during the treatment of 21 patients
      undergoing noninvasive ventilation, followed by interviews with 11 of the
      patients after treatment completion. Data were collected from December 2009
      January 2012. RESULTS: A substantive theory of striving for habitual well-being
      was developed. The theory included three phases: initiation, transition and
      determination. Each phase contained a set of subcategories to indicate the
      dimensions of and variations in the participants' behaviour. CONCLUSIONS: The
      substantive theory revealed that the patients' behaviour was related to their
      breathlessness, sensation of being restrained by the mask and head gear, and the
      side effects of noninvasive ventilation. RELEVANCE TO CLINICAL PRACTICE: This
      inter-relationship should be addressed in the use of noninvasive ventilation for
      the treatment of patients with chronic obstructive pulmonary disease to achieve
      treatment success.

PMID- 24028683
TI  - Trans fatty acids exacerbate dextran sodium sulphate-induced colitis by promoting
      the up-regulation of macrophage-derived proinflammatory cytokines involved in T
      helper 17 cell polarization.
AB  - Numerous reports have shown that a diet containing large amounts of trans fatty
      acids (TFAs) is a major risk factor for metabolic disorders. Although recent
      studies have shown that TFAs promote intestinal inflammation, the underlying
      mechanisms are unknown. In this study, we examined the effects of dietary fat
      containing TFAs on dextran sodium sulphate (DSS)-induced colitis. C57 BL/6 mice
      were fed a diet containing 1.3% TFAs (mainly C16:1, C18:1, C18:2, C20:1, C20:2
      and C22:1), and then colitis was induced with 1.5% DSS. Colonic damage was
      assessed, and the mRNA levels of proinflammatory cytokines and major regulators
      of T cell differentiation were measured. The TFA diet reduced survival and
      exacerbated histological damage in mice administered DSS compared with those fed
      a TFA-free diet. The TFA diet significantly elevated interleukin (IL)-6, IL
      12p40, IL-23p19 and retinoic acid-related orphan receptor (ROR)gammat mRNA levels
      in the colons of DSS-treated animals. Moreover, IL-17A mRNA levels were elevated
      significantly by the TFA diet, with or without DSS treatment. We also examined
      the expression of proinflammatory cytokines in lipopolysaccharide (LPS)
      stimulated RAW264.7 cells and peritoneal macrophages. These cells were exposed to
      TFAs (linoelaidic acid or elaidic acid) with or without LPS and the mRNA levels
      of various cytokines were measured. IL-23p19 mRNA levels were increased
      significantly by TFAs in the absence of LPS. Cytokine expression was also higher
      in LPS-stimulated cells exposed to TFAs than in unexposed LPS-stimulated cells.
      Collectively, our results suggest that TFAs exacerbate colonic inflammation by
      promoting Th17 polarization and by up-regulating the expression of
      proinflammatory cytokines in the inflamed colonic mucosa. 

PMID- 24028685
TI  - Highlighting the role of polymer length, carbohydrate size, and nucleic acid type
      in potency of glycopolycation agents for pDNA and siRNA delivery.
AB  - While nucleic acids such as small interfering RNA (siRNA) and plasmid DNA (pDNA)
      are promising research tools and therapeutic modalities, their potential in
      medical applications is limited by a fundamental mechanistic understanding and
      inadequate efficiency. Herein, two series of carbohydrate-based polycations were
      synthesized and examined that varied in the degree of polymerization (n), one
      containing trehalose [Tr4(n) series: Tr4(23), Tr4(55), Tr4(77)] and the other
      containing beta-cyclodextrin [CD4(n) series: CD4(10), CD4(26), CD4(39), CD4(143),
      CD4(239)]. In addition, two monosaccharide models were examined for comparison
      that contain tartaramidoamine (T4) and galactaramidoamine (G4 or Glycofect)
      repeats. Delivery profiles for pDNA were compared with those obtained for siRNA
      delivery and reveal that efficacy differs significantly as a function of
      carbohydrate type, nucleic acid type and dose, polymer length, and presence of
      excess polymer in the formulation. The Tr4 polymers yielded higher efficacy for
      pDNA delivery, yet the CD4 polymers achieved higher siRNA delivery and gene down
      regulation. The T4 and Glycofect derivatives, while efficient for pDNA delivery,
      were completely ineffective for siRNA delivery. A strong polymer length and dose
      dependence on target gene knockdown was observed for all polymers tested. Also,
      free polymer in solution (uncomplexed) was demonstrated to be a key factor in
      promoting siRNA uptake and gene down-regulation. 

PMID- 24028686
TI  - Insights on pH-dependent conformational changes of mosquito odorant binding
      proteins by molecular dynamics simulations.
AB  - Chemical recognition plays an important role for the survival and reproduction of
      many insect species. Odorant binding proteins (OBPs) are the primary components
      of the insect olfactory mechanism and have been documented to play an important
      role in the host-seeking mechanism of mosquitoes. They are "transport proteins"
      believed to transport odorant molecules from the external environment to their
      respective membrane targets, the olfactory receptors. The mechanism by which this
      transport occurs in mosquitoes remains a conundrum in this field. Nevertheless,
      OBPs have proved to be amenable to conformational changes mediated by a pH change
      in other insect species. In this paper, the effect of pH on the conformational
      flexibility of mosquito OBPs is assessed computationally using molecular dynamics
      simulations of a mosquito OBP "CquiOBP1" bound to its pheromone 3OG (PDB ID:
      3OGN). Conformational twist of a loop, driven by a set of well-characterized
      changes in intramolecular interactions of the loop, is demonstrated. The
      concomitant (i) closure of what is believed to be the entrance of the binding
      pocket, (ii) expansion of what could be an exit site, and (iii) migration of the
      ligand towards this putative exit site provide preliminary insights into the
      mechanism of ligand binding and release of these proteins in mosquitoes. The
      correlation of our results with previous experimental observations based on NMR
      studies help us provide a cardinal illustration on one of the probable dynamics
      and mechanism by which certain mosquito OBPs could deliver their ligand to their
      membrane-bound receptors at specific pH conditions. 

PMID- 24028688
TI  - Dimethyl sulfoxide induces oxidative stress in the yeast Saccharomyces
      cerevisiae.
AB  - Dimethyl sulfoxide (DMSO) is used as a cryoprotectant for the preservation of
      cells, including yeast, and as a solvent for chemical compounds. We report that
      DMSO induces oxidative stress in the yeast. Saccharomyces cerevisiae wt strain EG
      103 and its mutants Deltasod1, Deltasod2, and Deltasod1 Deltasod2 were used.
      Yeast were subjected to the action of 1-14% DMSO for 1 h at 28  degrees C. DMSO
      induced a concentration-dependent inhibition of yeast growth, the effect being
      more pronounced for mutants devoid of SOD (especially Deltasod1 Deltasod2). Cell
      viability was compromised. DMSO-concentration-dependent activity loss of
      succinate dehydrogenase, a FeS enzyme sensitive to oxidative stress, was
      observed. DMSO enhanced formation of reactive oxygen species, estimated with
      dihydroethidine in a concentration-dependent manner, the effect being again more
      pronounced in mutants devoid of superoxide dismutases. The content of cellular
      glutathione was increased with increasing DMSO concentrations, which may
      represent a compensatory response. Membrane fluidity, estimated by fluorescence
      polarization of DPH, was decreased by DMSO. These results demonstrate that DMSO,
      although generally considered to be antioxidant, induces oxidative stress in
      yeast cells.

PMID- 24028687
TI  - Parallel evolution of genome structure and transcriptional landscape in the
      Epsilonproteobacteria.
AB  - BACKGROUND: Gene reshuffling, point mutations and horizontal gene transfer
      contribute to bacterial genome variation, but require the genome to rewire its
      transcriptional circuitry to ensure that inserted, mutated or reshuffled genes
      are transcribed at appropriate levels. The genomes of Epsilonproteobacteria
      display very low synteny, due to high levels of reshuffling and reorganisation of
      gene order, but still share a significant number of gene orthologs allowing
      comparison. Here we present the primary transcriptome of the pathogenic
      Epsilonproteobacterium Campylobacter jejuni, and have used this for comparative
      and predictive transcriptomics in the Epsilonproteobacteria. RESULTS:
      Differential RNA-sequencing using 454 sequencing technology was used to determine
      the primary transcriptome of C. jejuni NCTC 11168, which consists of 992
      transcription start sites (TSS), which included 29 putative non-coding and stable
      RNAs, 266 intragenic (internal) TSS, and 206 antisense TSS. Several previously
      unknown features were identified in the C. jejuni transcriptional landscape, like
      leaderless mRNAs and potential leader peptides upstream of amino acid
      biosynthesis genes. A cross-species comparison of the primary transcriptomes of
      C. jejuni and the related Epsilonproteobacterium Helicobacter pylori highlighted
      a lack of conservation of operon organisation, position of intragenic and
      antisense promoters or leaderless mRNAs. Predictive comparisons using 40 other
      Epsilonproteobacterial genomes suggests that this lack of conservation of
      transcriptional features is common to all Epsilonproteobacterial genomes, and is
      associated with the absence of genome synteny in this subdivision of the
      Proteobacteria. CONCLUSIONS: Both the genomes and transcriptomes of
      Epsilonproteobacteria are highly variable, both at the genome level by combining
      and division of multicistronic operons, but also on the gene level by generation
      or deletion of promoter sequences and 5' untranslated regions. Regulatory
      features may have evolved after these species split from a common ancestor, with
      transcriptome rewiring compensating for changes introduced by genomic reshuffling
      and horizontal gene transfer.

PMID- 24028689
TI  - Curcumin conjugated silica nanoparticles for improving bioavailability and its
      anticancer applications.
AB  - Curcumin, a yellow bioactive component of Indian spice turmeric, is known to have
      a wide spectrum of biological applications. In spite of various astounding
      therapeutic properties, it lacks in bioavailability mainly due to its poor
      solubility in water. In this work, we have conjugated curcumin with silica
      nanoparticles to improve its aqueous solubility and hence to make it more
      bioavailable. Conjugation and loading of curcumin with silica nanoparticles was
      further examined with transmission electron microscope (TEM) and
      thermogravimetric analyzer. Cytotoxicity analysis of synthesized silica:curcumin
      conjugate was studied against HeLa cell lines as well as normal fibroblast cell
      lines. This study shows that silica:curcumin conjugate has great potential for
      anticancer application. 

PMID- 24028690
TI  - Kinetics of Th17 cytokines during telbivudine therapy in patients with chronic
      hepatitis B.
AB  - Th17 cells and the secreting cytokines play an important role in the immune
      response and inflammation that is induced by hepatitis B virus (HBV). However, it
      remains not fully elucidated how the antiviral agents affect Th17 cytokines and
      signal pathway. Telbivudine therapy has been proved to inhibit HBV replication
      effectively and to improve clinical outcome of chronic hepatitis B (CHB). Thus,
      in this study, the effect of decrease in viral load and liver dysfunction
      resulting from telbivudine treatment on Th17 cells and the related cytokines IL
      17, IL-22, and IL-23 were analyzed. Peripheral blood mononuclear cells and serum
      from twenty-four CHB patients were harvested at 0, 12, 24, 36, and 48 weeks after
      initiation of telbivudine treatment. In parallel to the reduction of HBV DNA and
      normalization of serum ALT, significant declines in circulating HBV-specific Th17
      cells and IL-22 production were found during antiviral therapy. The expression of
      serum IL-22 and IL-23, but not IL-17 also decreased during therapy. Our findings
      suggest that antiviral effect of telbivudine may attribute to both direct virus
      inhibition and regulation of inflammation, which further improve the
      understanding of pathogenesis of HBV infection and develop antiviral strategy for
      controlling viral hepatitis.

PMID- 24028691
TI  - Development of a comprehensive list of criteria for evaluating consumer education
      materials on colorectal cancer screening.
AB  - BACKGROUND: Appropriate patient information materials may support the consumer's
      decision to attend or not to attend colorectal cancer (CRC) screening tests
      (fecal occult blood test and screening colonoscopy). The aim of this study was to
      develop a list of criteria to assess whether written health information materials
      on CRC screening provide balanced, unbiased, quantified, understandable, and
      evidence-based health information (EBHI) about CRC and CRC screening. METHODS:
      The list of criteria was developed based on recommendations and assessment tools
      for health information in the following steps: (1) Systematic literature search
      in 13 electronic databases (search period: 2000-2010) and completed by an
      Internet search (2) Extraction of identified criteria (3) Grouping of criteria
      into categories and domains (4) Compilation of a manual of adequate answers
      derived from systematic reviews and S3 guidelines (5) Review by external experts
      (6) Modification (7) Final discussion with external experts. RESULTS: Thirty-one
      publications on health information tools and recommendations were identified. The
      final list of criteria includes a total of 230 single criteria in three generic
      domains (formal issues, presentation and understandability, and neutrality and
      balance) and one CRC-specific domain. A multi-dimensional rating approach was
      used whenever appropriate (e.g., rating for the presence, correctness,
      presentation and level of evidence of information). Free text input was allowed
      to ensure the transparency of assessment. The answer manual proved to be
      essential to the rating process. Quantitative analyses can be made depending on
      the level and dimensions of criteria. CONCLUSIONS: This comprehensive list of
      criteria clearly has a wider range of evaluation than previous assessment tools.
      It is not intended as a final quality assessment tool, but as a first step toward
      thorough evaluation of specific information materials for their adherence to EBHI
      requirements. This criteria list may also be used to revise leaflets and to
      develop evidence-based health information on CRC screening. After adjustment for
      different procedure-specific criteria, the list of criteria can also be applied
      to other cancer screening procedures.

PMID- 24028692
TI  - Neuropharmacological lesion localization in idiopathic Horner's syndrome in
      Golden Retrievers and dogs of other breeds.
AB  - OBJECTIVE: To investigate whether idiopathic Horner's syndrome (HS) in Golden
      Retrievers is an exclusively preganglionic disorder based on denervation
      hypersensitivity pharmacological testing with phenylephrine. ANIMALS STUDIED:
      Medical records of dogs presented with HS between 2000 and 2012. Dogs presented
      with additional ocular or systemic signs were excluded. PROCEDURES: Clinical data
      examined included age, sex, duration of clinical signs, ancillary diagnostic test
      results, and time to mydriasis on topical ocular application of 1% phenylephrine.
      Lesions were diagnosed as postganglionic (mydriasis within 20 min) or
      preganglionic (mydriasis between 20 and 45 min). RESULTS: Medical records of 21
      dogs of nine different breeds were included. An etiopathogenesis for Horner's
      syndrome was determined in five dogs, none of which were Golden Retrievers. All
      diagnoses correlated with pharmacological lesion localization. Ten Golden
      Retrievers were included (eight male and two female) with a mean age of 8.5 years
      (range: 4-13). Lesion localization was diagnosed as postganglionic in eight
      (mean: 10 min [range: 6-18]) and preganglionic in two Golden Retrievers (20 and
      24 min). All cases were unilateral and had completely resolved within 15 weeks
      (range: 11-20). Recurrence was not reported in any of the patients. CONCLUSIONS:
      Idiopathic postganglionic HS was diagnosed in eight of 10 Golden Retrievers
      contradicting previous reports of a purely preganglionic localization.
      Etiopathogenesis of canine idiopathic HS remains to be determined; nevertheless,
      a vascular etiology cannot be excluded. Future studies using magnetic resonance
      angiography may aid in clarifying the pathogenesis.

PMID- 24028695
TI  - Commentary: the role of "technovigilance" in improving care in hospitals.

PMID- 24028694
TI  - Improving quality and safety of care using "technovigilance": an ethnographic
      case study of secondary use of data from an electronic prescribing and decision
      support system.
AB  - CONTEXT: "Meaningful use" of electronic health records to improve quality of care
      has remained understudied. We evaluated an approach to improving patients' safety
      and quality of care involving the secondary use of data from a hospital
      electronic prescribing and decision support system (ePDSS). METHODS: We conducted
      a case study of a large English acute care hospital with a well-established
      ePDSS. Our study was based on ethnographic observations of clinical settings (162
      hours) and meetings (28 hours), informal conversations with clinical staff,
      semistructured interviews with ten senior executives, and the collection of
      relevant documents. Our data analysis was based on the constant comparative
      method. FINDINGS: This hospital's approach to quality and safety could be
      characterized as "technovigilance." It involved treating the ePDSS as a warehouse
      of data on clinical activity and performance. The hospital converted the
      secondary data into intelligence about the performance of individuals, teams, and
      clinical services and used this as the basis of action for improvement. Through a
      combination of rapid audit, feedback to clinical teams, detailed and critical
      review of apparent omissions in executive-led meetings, a focus on personal
      professional responsibility for patients' safety and quality care, and the
      correction of organizational or systems defects, technovigilance was-based on the
      hospital's own evidence-highly effective in improving specific indicators.
      Measures such as the rate of omitted doses of medication showed marked
      improvement. As do most interventions, however, technovigilance also had
      unintended consequences. These included the risk of focusing attention on aspects
      of patient safety made visible by the system at the expense of other, less
      measurable but nonetheless important, concerns. CONCLUSIONS: The secondary use of
      electronic data can be effective for improving specific indicators of care if
      accompanied by a range of interventions to ensure proper interpretation and
      appropriate action. But care is needed to avoid unintended consequences.

PMID- 24028696
TI  - High-reliability health care: getting there from here.
AB  - CONTEXT: Despite serious and widespread efforts to improve the quality of health
      care, many patients still suffer preventable harm every day. Hospitals find
      improvement difficult to sustain, and they suffer "project fatigue" because so
      many problems need attention. No hospitals or health systems have achieved
      consistent excellence throughout their institutions. High-reliability science is
      the study of organizations in industries like commercial aviation and nuclear
      power that operate under hazardous conditions while maintaining safety levels
      that are far better than those of health care. Adapting and applying the lessons
      of this science to health care offer the promise of enabling hospitals to reach
      levels of quality and safety that are comparable to those of the best high
      reliability organizations. METHODS: We combined the Joint Commission's knowledge
      of health care organizations with knowledge from the published literature and
      from experts in high-reliability industries and leading safety scholars outside
      health care. We developed a conceptual and practical framework for assessing
      hospitals' readiness for and progress toward high reliability. By iterative
      testing with hospital leaders, we refined the framework and, for each of its
      fourteen components, defined stages of maturity through which we believe
      hospitals must pass to reach high reliability. FINDINGS: We discovered that the
      ways that high-reliability organizations generate and maintain high levels of
      safety cannot be directly applied to today's hospitals. We defined a series of
      incremental changes that hospitals should undertake to progress toward high
      reliability. These changes involve the leadership's commitment to achieving zero
      patient harm, a fully functional culture of safety throughout the organization,
      and the widespread deployment of highly effective process improvement tools.
      CONCLUSIONS: Hospitals can make substantial progress toward high reliability by
      undertaking several specific organizational change initiatives. Further research
      and practical experience will be necessary to determine the validity and
      effectiveness of this framework for high-reliability health care.

PMID- 24028698
TI  - Tragic choices and moral compromise: the ethics of allocating kidneys for
      transplantation.
AB  - CONTEXT: For almost a decade, the Kidney Transplantation Committee of the United
      Network for Organ Sharing has been striving to revise its approach to allocating
      kidneys from deceased donors for transplantation. Two fundamental values,
      equality and efficiency, are central to distributing this scarce resource. The
      prevailing approach gives primacy to equality in the temporal form of first-come,
      first-served, whereas the motivation for a new approach is to redeem efficiency
      by increasing the length of survival of transplanted kidneys and their
      recipients. But decision making about a better way of allocating kidneys
      flounders because it is constrained by the amorphous notion of "balancing"
      values. METHODS: This article develops a more fitting, productive approach to
      resolving the conflict between equality and efficiency by embedding the notion of
      compromise in the analysis of a tragic choice provided by Guido Calabresi and
      Philip Bobbitt. For Calabresi and Bobbitt, the goals of public policy with
      respect to tragic choices are to limit tragedy and to deal with the irreducible
      minimum of tragedy in the least offensive way. Satisfying the value of efficiency
      limits tragedy, and satisfying the value of equality deals with the irreducible
      minimum of tragedy in the least offensive way. But both values cannot be
      completely satisfied simultaneously. Compromise is occasioned when not all the
      several obligations that exist in a situation can be met and when neglecting some
      obligations entirely in order to fulfill others entirely is improper. Compromise
      is amalgamated with the notion of a tragic choice and then used to assess
      proposals for revising the allocation of kidneys considered by the Kidney
      Transplantation Committee. FINDINGS: Compromise takes two forms in allocating
      kidneys: it occurs within particular approaches to allocating kidneys because
      neither equality nor efficiency can be fully satisfied, and it occurs over the
      course of sequential approaches to allocating kidneys that cycle between
      preferring equality and efficiency. Ross and colleagues' Equal Opportunity
      Supplemented by Fair Innings proposal for allocating kidneys best exemplifies the
      rationality of compromise as a way of achieving the goals of making a tragic
      choice. CONCLUSIONS: The attempt to design a policy for allocating kidneys from
      deceased donors for transplantation by balancing the values of equality and
      efficiency is misguided and unhelpful. Instead policymaking should both
      incorporate compromise into discrete approaches to allocating kidneys and extend
      compromise over sequential approaches to allocating kidneys.

PMID- 24028697
TI  - Is personality associated with health care use by older adults?
AB  - CONTEXT: The patterns of health care utilization in the United States pose well
      established challenges for public policy. Although economic and sociological
      research has resulted in considerable knowledge about what influences the use of
      health services, the psychological literature in this area is underdeveloped.
      Importantly, it is not known whether personality traits are associated with older
      adults' use of acute and long-term care services. METHODS: Data were collected
      from 1,074 community-dwelling seniors participating in a Medicare demonstration.
      First they completed a self-report questionnaire measuring the "Big Five"
      personality traits: Neuroticism, Extraversion, Openness to Experience,
      Agreeableness, and Conscientiousness. During the next two years, the participants
      maintained daily journals of their use of health care services. We used
      regression models based on the Andersen behavioral model of health care
      utilization to test for associations. FINDINGS: Our hypothesis that higher
      Neuroticism would be associated with greater health care use was confirmed for
      three services-probability of any emergency department (ED) use, likelihood of
      any custodial nursing home use, and more skilled nursing facility (SNF) days for
      SNF users-but was disconfirmed for hospital days for those hospitalized. Higher
      Openness to Experience was associated with a greater likelihood of custodial home
      care use, and higher Agreeableness and lower Conscientiousness with a higher
      probability of custodial nursing home use. For users, lower Openness was
      associated with more ED visits and SNF days, and lower Conscientiousness with
      more ED visits. For many traits with significant associations, the predicted use
      was 16 to 30 percent greater for people high (low) versus low (high) in specific
      traits. CONCLUSIONS: Personality traits are associated with Medicare
      beneficiaries' use of many expensive health care services, findings that have
      implications for health services research and policy. Accordingly, person
      centered interventions, population-based translational effectiveness programs,
      and other personalized approaches that leverage the profound advances in
      personality psychology in recent decades should be considered.

PMID- 24028699
TI  - Shifting the paradigm: using HIV surveillance data as a foundation for improving
      HIV care and preventing HIV infection.
AB  - CONTEXT: Reducing HIV incidence in the United States and improving health
      outcomes for people living with HIV hinge on improving access to highly effective
      treatment and overcoming barriers to continuous treatment. Using laboratory tests
      routinely reported for HIV surveillance to monitor individuals' receipt of HIV
      care and contacting them to facilitate optimal care could help achieve these
      objectives. Historically, surveillance-based public health intervention with
      individuals for HIV control has been controversial because of concerns that risks
      to privacy and autonomy could outweigh benefits. But with the availability of
      lifesaving, transmission-interrupting treatment for HIV infection, some health
      departments have begun surveillance-based outreach to facilitate HIV medical
      care. METHODS: Guided by ethics frameworks, we explored the ethical arguments for
      changing the uses of HIV surveillance data. To identify ethical, procedural, and
      strategic considerations, we reviewed the activities of health departments that
      are using HIV surveillance data to contact persons identified as needing
      assistance with initiating or returning to care. FINDINGS: Although privacy
      concerns surrounding the uses of HIV surveillance data still exist, there are
      ethical concerns associated with not using HIV surveillance to maximize the
      benefits from HIV medical care and treatment. Early efforts to use surveillance
      data to facilitate optimal HIV medical care illustrate how the ethical burdens
      may vary depending on the local context and the specifics of implementation.
      Health departments laid the foundation for these activities by engaging
      stakeholders to gain their trust in sharing sensitive information; establishing
      or strengthening legal, policy and governance infrastructure; and developing
      communication and follow-up protocols that protect privacy. CONCLUSIONS: We
      describe a shift toward using HIV surveillance to facilitate optimal HIV care.
      Health departments should review the considerations outlined before implementing
      new uses of HIV surveillance data, and they should commit to an ongoing review of
      activities with the objective of balancing beneficence, respect for persons, and
      justice.

PMID- 24028702
TI  - Identification of the haemolytic activity of Malassezia species.
AB  - Malassezia species are part of the normal skin flora and are associated with a
      number of human and animal skin diseases. However, the mechanisms that mediate
      infection and host-fungal interactions are poorly understood. The haemolytic
      activity of several microorganisms is considered a factor that contributes to
      pathogenicity of the organism to humans and animals. This virulence factor was
      previously identified in several pathogenic fungi that cause systemic mycoses,
      such as Aspergillus and Candida. In this study, the haemolytic activity of six
      major Malassezia species, including M. furfur, M. globosa, M. pachydermatis, M.
      restricta, M. slooffiae and M. sympodialis, was investigated. The haemolytic
      activity of these species was tested on tryptone soya agar with 5% sheep blood.
      All the examined Malassezia species produced a halo zone of complete haemolysis.
      A quantitative analysis of the haemolytic activity was performed by incubating
      sheep erythrocytes with the extraction from culture of each Malassezia species.
      Interestingly, M. globosa and M. restricta showed significantly high haemolytic
      activity compared with the other Malassezia species. In addition, M. globosa also
      exhibited stable haemolytic activity after treatment at 100  degrees C and in the
      presence of some proteases, indicating that this haemolytic factor is different
      from those of other fungi. 

PMID- 24028703
TI  - A two-centre comparative evaluation of new automated assays for von Willebrand
      factor ristocetin cofactor activity and antigen.
AB  - von Willebrand disease (VWD) is caused by a quantitative and/or qualitative
      deficiency of the von Willebrand factor (VWF). The laboratory diagnosis of VWD is
      dependent on the measurement of VWF antigen (VWF:Ag) and ristocetin cofactor
      activity (VWF:RCo). The aim of this study was to undertake a two-centre
      evaluation of two new automated VWF:Ag and VWF:RCo assays systems from
      Instrumentation Laboratory (Bedford, USA). Using the two new analytical systems
      that operated with different detection principles: immunoturbidimetric (TOP500
      analyser) and chemiluminescent (AcuStar analyser), VWF:Ag and VWF:RCo levels were
      determined in samples from 171 healthy normal subjects, 80 VWD patients (16 type
      1, 58 type 2 and 6 type 3) and 7 acquired von Willebrand syndrome patients. With
      commercial lyophilized normal and pathological plasmas VWF: Ag and VWF:RCo assays
      performed on both analysers exhibited low levels of inter-assay imprecision
      (AcuStar: CV% range 3.3-6.9; TOP500: CV% range 2.6-6.3). Samples from normal
      healthy subjects (range: VWF:Ag 44.6-173.9 IU dL(-1) ; VWF:RCo 43.1-191.5 IU dL(
      1)) and patients (range: VWF:Ag <0.3-115.1 IU dL(-1) ; VWF:RCo <0.5-57.2 IU dL(
      1)) showed a good correlation between the two VWF:Ag and VWF:RCo methods (rs =
      0.92 and 0.82 respectively), with only a few inconsistent cases among the
      patients' samples evaluated. The chemiluminescent assays had a lower limit of
      detection for both VWF:Ag and VWF:RCo compared to immunoturbidimetric tests (0.3
      IU dL(-1) vs. 2.2 IU dL(-1) and 0.5 IU dL(-1) vs. 4.4 IU dL(-1) respectively).
      The TOP500 and AcuStar VWF:Ag and VWF:RCo assays were precise and compare well
      between centres, making these systems suitable for the diagnosis of VWD in non
      specialized and reference laboratories.

PMID- 24028700
TI  - How contexts and issues influence the use of policy-relevant research syntheses:
      a critical interpretive synthesis.
AB  - CONTEXT: Evidence briefs have emerged as a promising approach to synthesizing the
      best available research evidence for health system policymakers and stakeholders.
      An evidence brief may draw on systematic reviews and many other types of policy
      relevant information, including local data and studies, to describe a problem,
      options for addressing it, and key implementation considerations. We conducted a
      systematic review to examine the ways in which context- and issue-related factors
      influence the perceived usefulness of evidence briefs among their intended users.
      METHODS: We used a critical interpretive synthesis approach to review both
      empirical and nonempirical literature and to develop a model that explains how
      context and issues influence policymakers' and stakeholders' views of the utility
      of evidence briefs prepared for priority policy issues. We used a "compass"
      question to create a detailed search strategy and conducted electronic searches
      in CINAHL, EMBASE, HealthSTAR, IPSA, MEDLINE, OAIster (gray literature), ProQuest
      A&I Theses, ProQuest (Sociological Abstracts, Applied Social Sciences Index and
      Abstracts, Worldwide Political Science Abstracts, International Bibliography of
      Social Sciences, PAIS, Political Science), PsychInfo, Web of Science, and
      WilsonWeb (Social Science Abstracts). Finally, we used a grounded and
      interpretive analytic approach to synthesize the results. FINDINGS: Of the 4,461
      papers retrieved, 3,908 were excluded and 553 were assessed for "relevance," with
      137 included in the initial sample of papers to be analyzed and an additional 23
      purposively sampled to fill conceptual gaps. Several themes emerged: (1) many
      established types of "evidence" are viewed as useful content in an evidence
      brief, along with several promising formatting features; (2) contextual factors,
      particularly the institutions, interests, and values of a given context, can
      influence views of evidence briefs; (3) whether an issue is polarizing and
      whether it is salient (or not) and familiar (or not) to actors in the policy
      arena can influence views of evidence briefs prepared for that issue; (4)
      influential factors can emerge in several ways (as context driven, issue driven,
      or a result of issue-context resonance); (5) these factors work through two
      primary pathways, affecting either the users or the producers of briefs; and (6)
      these factors influence views of evidence briefs through a variety of mechanisms.
      CONCLUSIONS: Those persons funding and preparing evidence briefs need to consider
      a variety of context- and issue-related factors when deciding how to make them
      most useful in policymaking.

PMID- 24028705
TI  - Deficiency of antithrombin and protein C gene in 202 Chinese venous
      thromboembolism patients.
AB  - INTRODUCTION: Antithrombin and protein C gene deficiencies are commonly inherited
      risk factors for VTE patients. We aim to investigate the deficiency of these two
      gene in 202 Chinese patients with venous thromboembolism (VTE). METHODS:
      Antithrombin activity (AT: A) and protein C activity (PC: A) were measured in 202
      VTE patients, and for those with unexplainable low results, PCR and direct
      sequencing of the related genes were carried out. RESULTS: Deficiency levels of
      antithrombin and protein C gene were found to be 2% and 8%, respectively. AT or
      PC hereditary deficiency can be found in 10% patients with VTE. CONCLUSION:
      Protein C gene deficiency might be more prevalent than AT gene deficiency in
      Chinese VTE patients. Functional assay combined with genetic analysis is useful
      in the diagnosis of inherited defects in VTE patients.

PMID- 24028704
TI  - On the design of clone-based haplotyping.
AB  - BACKGROUND: Haplotypes are important for assessing genealogy and disease
      susceptibility of individual genomes,but are difficult to obtain with routine
      sequencing approaches. Experimental haplotype reconstruction based on assembling
      fragments of individual chromosomes is promising, but with variable yields due to
      incompletely understood parameter choices. RESULTS: We parameterize the clone
      based haplotyping problem in order to provide theoretical and empirical
      assessments of the impact of different parameters on haplotype assembly. We
      confirm the intuition that long clones help link together heterozygous variants
      and thus improve haplotype length. Furthermore, given the length of the clones,
      we address how to choose the other parameters, including number of pools, clone
      coverage and sequencing coverage, so as to maximize haplotype length. We model
      the problem theoretically and show empirically the benefits of using larger
      clones with moderate number of pools and sequencing coverage. In particular,
      using 140 kb BAC clones, we construct haplotypes for a personal genome and
      assemble haplotypes with N50 values greater than 2.6 Mb. These assembled
      haplotypes are longer and at least as accurate as haplotypes of existing clone
      based strategies, whether in vivo or in vitro. CONCLUSIONS: Our results provide
      practical guidelines for the development and design of clone-based methods to
      achieve long range, high-resolution and accurate haplotypes.

PMID- 24028706
TI  - Contribution of proteomics in the identification of novel proteins associated
      with plant growth.
AB  - The epidermis is not only the interphase between the plant and the environment
      but also a growth-limiting tissue. Understanding the initiation and regulation of
      its expansion growth is essential for addressing the need for more food and fuel.
      We used mass spectrometry to identify proteins from auxin (indole-3-acetic acid;
      IAA)-induced rapidly growing corn (Zea mays) coleoptiles to find possible
      candidates controlling this growth as well as the underlying cell wall and
      cuticle biosynthesis. Excised sections were incubated for 4 h in the absence or
      presence of IAA, protein extracted, and analyzed using LC-ESI-MS/MS. Of 86
      proteins identified, 15 showed a predicted association with cell wall/cuticle
      biosynthesis or trafficking machinery; four identifications revealed novel
      proteins of unknown function. In parallel, real-time PCR indicated that the
      steady-state mRNA levels of genes with a known or predicted role in cell-wall
      biosynthesis increase upon treatment with auxin. Importantly, genes encoding two
      of the hypothetical proteins also show higher levels of mRNA; additionally, their
      gene expression is down-regulated as coleoptile growth ceases and up-regulated in
      expanding leaves. This suggests a major role of those novel proteins in the
      regulation of processes related to cell and organ expansion and thus plant
      growth. 

PMID- 24028707
TI  - Interface-engineered resistive switching: CeO(2) nanocubes as high-performance
      memory cells.
AB  - We reported a novel and facile approach to fabricate self-assembled CeO2 nanocube
      based resistive-switching memory device. The device was found to exhibit
      excellent bipolar resistive-switching characteristics with a high resistance
      state (HRS/OFF) to low resistance state (LRS/ON) ratio of 10(4), better
      uniformity, and stability up to 480 K. The presence of oxygen vacancies and their
      role was discussed to explain the resistive-switching phenomenon in the
      fabricated devices. Further, the effect of the film thickness on carrier
      concentrations and estimated electric field strength with the switching (OFF/ON)
      ratio were also discussed. 

PMID- 24028708
TI  - Association of dialysate calcium concentration with fetuin A level and carotid
      intima-media thickness in peritoneal dialysis patients.
AB  - Serum fetuin A has been shown to be associated with the risk of vascular
      calcification and atherosclerosis, and it can predict the onset of cardiovascular
      mortality in dialysis patients. The carotid intima-media thickness (cIMT) is an
      accessible and reliable method to identify the subclinical atherosclerosis. The
      aim of this study was to investigate the relationships between dialysate calcium
      concentrations and fetuin A or cIMT in patients undergoing peritoneal dialysis
      (PD). Forty patients, newly diagnosed end-stage renal disease (ESRD) and
      undergoing peritoneal dialysis, were enrolled in the study, with a calcium
      content of the peritoneal dialysis (PD) solution of 1.25 mmol/L in 20 patients
      (low-Ca group) and 1.75 mmol/L in 20 patients (standard-Ca group). The patients
      were followed up for 12 months after the PD conducted. Serum fetuin A was
      determined using a human fetuin A enzyme-linked immunosorbent assay kit and cIMT
      was detected using ultrasonic wave. We observed no difference between two groups
      with regard to the baseline data of fetuin A, cIMT, calcium, phosphorus, calcium
      phosphorus product, high sensitivity CRP (hsCRP), parathyroid hormone (PTH), or
      lipid parameters. After 12 months follow-up, fetuin A (263.92 +/- 16.1 vs. 282.76
      +/- 21.0, p = 0.017) and calcium-phosphorus product (39.85 +/- 7.76 vs. 47.50 +/-
      6.65, p = 0.009) were obviously lower in the low-Ca group than standard-Ca group,
      the other serum parameters were not different between these two groups. Compared
      with baseline data, serum fetuin A concentration significantly reduced in low-Ca
      group ( p < 0.05). The number of patients with increased cIMT and newly occurring
      cardiovascular events in the low-Ca group were significantly reduced than
      standard-Ca group ( p < 0.05). In conclusion, our data suggest that low calcium
      dialysate treatment is associated with the decreased serum fetuin A concentration
      and serum calcium-phosphorus product, and it is associated with the reduced
      number of PD patients with increased cIMT or with newly occurring cardiovascular
      events. However, more studies with lager sample size should be performed in the
      future.

PMID- 24028709
TI  - Hematologic toxicities associated with mTOR inhibitors temsirolimus and
      everolimus in cancer patients: a systematic review and meta-analysis.
AB  - BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors, temsirolimus and
      everolimus, are currently approved for the treatment of several malignancies.
      Hematological toxicities have been reported with these drugs, but overall
      incidence and relative risk remains undefined. We perform an up-to-date meta
      analysis to determine the incidence and risk of hematologic toxicities associated
      with mTOR inhibitors. METHODS: Several databases were searched, including PubMed,
      Embase and Cochrane databases. Eligible studies included prospective phase II and
      III trials of temsirolimus and everolimus with adequate safety data profile
      reporting anemia, leucopenia, neutropenia or thrombocytopenia. Overall incidence
      rates, relative risk (RR), and 95% confidence intervals (CI) were calculated by
      using either random effects or fixed effects models according to the
      heterogeneity of included studies. RESULTS: A total of 5436 patients with a
      variety of solid tumors from 26 clinical trials were included for the meta
      analysis. The overall incidences of mTOR inhibitor associated all-grade and high
      grade hematologic toxicities were, respectively: anemia--38.8% and 7.5%;
      leucopenia--19.6% and 1.8%; neutropenia--14.9% and 5.6%; thrombocytopenia--33.1%
      and 3.6%. Compared to placebo/control arms, mTOR inhibitors were associated with
      a significantly increased risk of all-grade (RR 2.05, 95% CI: 1.52-2.77; p <
      0.001) and high-grade anemia (RR 1.57, 95% CI: 1.20-2.05; p = 0.001), all-grade
      (RR 6.03, 95% CI: 2.76-13.14; p < 0.001) and high-grade thrombocytopenia (RR
      2.73, 95% CI: 1.87-3.99; p < 0.001). Additionally, a non-significantly increased
      risk of all-grade leucopenia (RR 1.46, 95% CI: 0.66-3.23; p = 0.34) and
      neutropenia (RR 1.77, 95% CI: 0.80-3.93; p = 0.16) was observed in the mTOR
      inhibitor group, while the risk of high-grade leucopenia (RR 0.53, 95% CI: 0.31
      0.90, p = 0.019) and neutropenia (RR 0.96, 95% CI: 0.62-1.51; p = 0.87) did not
      increase. Similar results were also observed in sub-group analysis according to
      mTOR inhibitor based regimens. CONCLUSIONS: The use of mTOR inhibitors is
      associated with a significant increase in the risk of developing all-grade and
      high-grade anemia and thrombocytopenia compared with placebo/control arms.

PMID- 24028710
TI  - Development of a slide agglutination assay for detection of blastomycosis.
AB  - Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitides,
      which is endemic to eastern regions of the USA, is commonly misdiagnosed as a
      viral or bacterial infection and therefore treated improperly. Over the years,
      many immunodiagnostic assays to aid in the diagnosis of blastomycosis have been
      developed; however, a reliable assay for use in local clinics still remains
      elusive. Procedures for a slide agglutination assay for detection of antibody in
      serum from rabbits immunized with B. dermatitidis were evaluated with antigenic
      preparations from B. dermatitidis adsorbed to polystyrene microparticles. Yeast
      phase lysates from five isolates of B. dermatitides: namely ER-593 (Eagle River,
      WI, USA), ER-598 (Eagle River, WI, USA), 48938 (India), B5896 (Mt. Iron, MN,
      USA), and T-58 (TN, USA) were evaluated for their sensitivity and specificity.
      Sensitivities of the lysates ranged from 29% to 83% whereas specificities ranged
      from 13% to 100%. Lysate ER-593 provided the most promising results with a
      sensitivity of 82% and specificity of 100%. This study provides suggests that a
      simple rapid slide agglutination assay for detecting blastomycosis may be used
      for screening patients with suspected B. dermatitidis infection. 

PMID- 24028711
TI  - An evaluation of emergency medical services stroke protocols and scene times.
AB  - BACKGROUND: Acute stroke patients require immediate medical attention. Therefore,
      American Stroke Association guidelines recommend that for suspected stroke cases,
      emergency medical services (EMS) personnel spend less than 15 minutes on-scene at
      least 90% of the time. However, not all EMS providers include specific scene time
      limits in their stroke patient care protocols. OBJECTIVE: We sought to determine
      whether having a protocol with a specific scene time limit was associated with
      less time EMS spent on scene. Methods. Stroke protocols from the 100 EMS systems
      in North Carolina were collected and abstracted for scene time instructions.
      Suspected stroke events occurring in 2009 were analyzed using data from the North
      Carolina Prehospital Medical Information System. Scene time was defined as the
      time from EMS arrival at the scene to departure with the patient. Quantile
      regression was used to estimate how the 90th percentile of the scene time
      distribution varied by systems with protocol instructions limiting scene time,
      adjusting for system patient volume and metropolitan status. RESULTS: In 2009, 23
      EMS systems in North Carolina had no instructions regarding scene time; 73 had
      general instructions to minimize scene time; and 4 had a specific limit for scene
      time (i.e., 10 or 15 min). Among 9,723 eligible suspected stroke events, mean
      scene time was 15.9 minutes (standard deviation 6.9 min) and median scene time
      was 15.0 minutes (90th percentile 24.3 min). In adjusted quantile regression
      models, the estimated reduction in the 90th percentile scene time, comparing
      protocols with a specific time limit to no instructions, was 2.2 minutes (95%
      confidence interval 1.3, 3.1 min). The difference in 90th percentile scene time
      between general and absent instructions was not statistically different (0.7 min
      [95% confidence interval -0.1, 1.4 min]). CONCLUSION: Protocols with specific
      scene time limits were associated with EMS crews spending less time at the scene
      while general instructions were not. These findings suggest EMS systems can
      modestly improve scene times for stroke by specifying a time limit in their
      protocols.

PMID- 24028712
TI  - Hypoglossal nerve monitoring, a potential application of intraoperative nerve
      monitoring in head and neck surgery.
AB  - BACKGROUND: Intraoperative nerve monitoring (IONM) has many applications in
      different surgical fields. In head and neck surgery, IONM has been used to
      perform surgery of the parotid, thyroid and parathyroid glands, preserving the
      facial and recurrent nerves. However, hypoglossal nerve neuromonitoring has not
      been addressed with such relevance. MATERIAL AND METHODS: A retrospective review
      of surgeries performed on patients with special tongue and floor of mouth
      conditions was undertaken to examine the indications that prompted its use.
      Particular attention was given to the pathology, intraoperative findings and the
      final outcome of each patient. RESULTS: Four patients, aged between 6 years and
      68 years, with complex oral tongue and floor of mouth lesions were reviewed.
      Three patients were male, aged 22 years and younger, and two of these patients
      had oral tongue cancers with previous surgery. Oral tongue and neck conditions
      are challenging since the functions of the hypoglossal nerve are put at risk. The
      use of IONM technology allowed us to preserve nerve functions, speech and
      swallowing. CONCLUSIONS: Although IONM of the hypoglossal nerve is not a common
      indication in tongue and floor of mouth lesions, under special conditions its
      application can be extrapolated to challenging surgical cases, like the ones
      described.

PMID- 24028714
TI  - I2/TBHP-catalyzed chemoselective amination of indoles.
AB  - A novel I2/TBHP-mediated direct oxidative diamination reaction of indoles with
      anilines was developed. The reaction proceeded smoothly under aqueous and open
      air reaction conditions. This protocol provides a practical synthetic method for
      the synthesis of Tryptanthrin and the construction of N-C3 linked
      pyrrolidinoindolines which is the core structure of Psychotrimine. 

PMID- 24028713
TI  - Clostridium thermocellum transcriptomic profiles after exposure to furfural or
      heat stress.
AB  - BACKGROUND: The thermophilic anaerobe Clostridium thermocellum is a candidate
      consolidated bioprocessing (CBP) biocatalyst for cellulosic ethanol production.
      It is capable of both cellulose solubilization and its fermentation to produce
      lignocellulosic ethanol. Intolerance to stresses routinely encountered during
      industrial fermentations may hinder the commercial development of this organism.
      A previous C. thermocellum ethanol stress study showed that the largest
      transcriptomic response was in genes and proteins related to nitrogen uptake and
      metabolism. RESULTS: In this study, C. thermocellum was grown to mid-exponential
      phase and treated with furfural or heat to a final concentration of 3 g.L-1 or 68
      degrees C respectively to investigate general and specific physiological and
      regulatory stress responses. Samples were taken at 10, 30, 60 and 120 min post
      shock, and from untreated control fermentations, for transcriptomic analyses and
      fermentation product determinations and compared to a published dataset from an
      ethanol stress study. Urea uptake genes were induced following furfural stress,
      but not to the same extent as ethanol stress and transcription from these genes
      was largely unaffected by heat stress. The largest transcriptomic response to
      furfural stress was genes for sulfate transporter subunits and enzymes in the
      sulfate assimilatory pathway, although these genes were also affected late in the
      heat and ethanol stress responses. Lactate production was higher in furfural
      treated culture, although the lactate dehydrogenase gene was not differentially
      expressed under this condition. Other redox related genes such as a copy of the
      rex gene, a bifunctional acetaldehyde-CoA/alcohol dehydrogenase and adjacent
      genes did show lower expression after furfural stress compared to the control,
      heat and ethanol fermentation profiles. Heat stress induced expression from
      chaperone related genes and overlap was observed with the responses to the other
      stresses. This study suggests the involvement of C. thermocellum genes with
      functions in oxidative stress protection, electron transfer, detoxification,
      sulfur and nitrogen acquisition, and DNA repair mechanisms in its stress
      responses and the use of different regulatory networks to coordinate and control
      adaptation. CONCLUSIONS: This study has identified C. thermocellum gene
      regulatory motifs and aspects of physiology and gene regulation for further
      study. The nexus between future systems biology studies and recently developed
      genetic tools for C. thermocellum offers the potential for more rapid strain
      development and for broader insights into this organism's physiology and
      regulation.

PMID- 24028715
TI  - [Interpretations for expert consensus on the diagnosis and treatment of
      paroxysmal nocturnal hemoglobinuria].

PMID- 24028716
TI  - [Changes of transcription factors Bcl-6, Foxp3 and RORgammat in CD4(+) cells in
      bone marrow of immuno-related hematocytopenia].
AB  - OBJECTIVE: To evaluate the possible mechanism of transcription factors B cell
      lymphoma 6 (Bcl-6) , forkhead/winged helix transcription factor 3 (Foxp3) and
      retinoic acid related orphan receptor (RORgammat) in CD4(+) T cells for immuno
      related hematocytopenia (IRH). METHODS: CD4(+) T cells were harvested from 40 IRH
      patients, 38 aplastic anemia subjects and 25 normal controls and separated by
      magnetic activated cell sorting (MACS). Then the expressions of transcription
      factors of Foxp3, RORgamma and Bcl-6 in CD4(+) T cells were measured by real time
      fluorescent quantitative-polymerase chain reaction (QRT-PCR). RESULTS: Auto
      antibody was detected on CD34(+) cells (67.5% (27/40) ), CD15(+) cells (65.0%
      (26/40)), GlyA(+) cells (75.0% (30/40) ), auto-antibody involving three, two or
      one myeloid cell were detected in 27.5% (11/40), 52.5% (21/40), 20.0% (8/40) of
      IRH patients. Compensatory increase of Foxp3 mRNA was found in IRH (0.124 (0.073
      0.198) vs 0.071 (0.046-0.118), P < 0.05). The expression of Bcl-6 was higher
      (2.243 (0.854-4.544) vs 1.211 (0.131-2.816), P < 0.05). Compared to aplastic
      anemia, the expression of RORgammat was lower in IRH (0.133 (0.068-0.189) vs
      0.290 (0.138-0.480), P < 0.01) and the ratio of Treg/Th17 shifted to Th17 in
      patients with aplastic anemia (Foxp3/RORgammat ratio,0.500 (0.240-0.795) vs 0.975
      (0.483-1.416), P < 0.01). CONCLUSION: As one kind of bone marrow failures caused
      by autoantibody to bone marrow cells, IRH may occur due to a high expression of
      Bcl-6 in CD4(+) T cells, its immunopathogenesis is different from that of
      aplastic anemia.

PMID- 24028718
TI  - [Change and significance of Th22 cells in patients with aplastic anemia].
AB  - OBJECTIVE: To explore the proportion of Th22 cells in peripheral blood of
      patients with aplastic anemia (AA) and evaluate its significance. METHODS: From
      January 2011 to June 2012, a total of 47 AA patients were recruited and divided
      into 4 groups: severe aplastic anemia (SAA) pre-therapy (group A, n = 11), non
      severe aplastic anemia (NSAA) pre-therapy (group B, n = 12), SAA post-therapy
      (group C, n = 12), NSAA post-therapy (group D, n = 12) and healthy donor controls
      (n = 12). The proportion of Th22 cells in peripheral blood of each group was
      evaluated by flow cytometry. The cytokines interleukin-22 (IL-22), transforming
      growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) were measured by ELISA. And the level of IL-22 mRNA was
      examined by reverse transcription-PCR (RT-PCR). RESULTS: The percentage of Th22
      cells and the level of IL-22, TNF-alpha, IL-6 and IL-22 mRNA in group A (4.3% +/-
      1.4%, (57 +/- 17) ng/L, (497 +/- 123) ng/L, (323 +/- 88) ng/L, 1.65 +/- 0.51) and
      group C (2.6% +/- 0.6%, (34 +/- 10) ng/L, (314 +/- 79) ng/L, (187 +/- 45) ng/L,
      0.92 +/- 0.28) were significantly higher than that in control group (1.2% +/-
      0.3%, (19 +/- 6) ng/L, (228 +/- 50) ng/L, (134 +/- 26) ng/L, 0.47 +/- 0.09,all P
      < 0.05). The percentage of Th22 cells and the level of IL-22, TNF-alpha , IL-6
      and IL-22 mRNA in group A were higher than those in group C (all P < 0.05). NSAA
      patients had similar results. The percentage of Th22 cells and the level of IL
      22, TNF-alpha , IL-6 and IL-22 mRNA in group A were higher than those in group B
      (all P < 0.05). But the level of TGF-beta in groups A and C were significantly
      lower than that in control group ((3.4 +/- 1.1) and (5.8 +/- 1.7) vs (9.7 +/-
      2.8) ng/L, P < 0.05). And the level of TGF-beta in group A was lower than that of
      group B (P < 0.05). CONCLUSIONS: The number of Th22 cells is elevated in AA
      patients. Th22 cells may be positively correlated with the development of AA. And
      a higher level of TNF-alpha, IL-6 and a lower level of TGF-beta promote the
      differentiation of Th22 cells.

PMID- 24028717
TI  - [Telomere length and gene expression of shelterin in CD3(+) T cell of severe
      aplastic anemia patients].
AB  - OBJECTIVE: To explore the changes in telomere length and gene expression of
      complex shelterin (composed of 6 core components: TRF1, TRF2, POT1, TIN2, TPP1
      and RAP1) in severe aplastic anemia (SAA). METHODS: Bone marrow samples were
      obtained from 20 SAA patients and 10 normal controls. CD3(+)T cells were sorted
      by immunomagnetic separation. Telomere length was tested by Southern blot and the
      gene expressions of TRF1, TRF2, POT1, TIN2, TPP1 and RAP1 were detected by
      reverse transcription-PCR(RT-PCR). RESULTS: Telomeres of CD3(+)T cells were found
      significantly shorter in SAA untreated ((4.4 +/- 1.1) kb, n = 9) and recovering
      groups((5.8 +/- 1.0) kb, n = 11) than control group ((9.2 +/- 3.3) kb, P < 0.05).
      Telomere length of CD3(+)T cells shortened with TH/S decreasing (r = 0.564, P =
      0.029). The mRNA expression of POT1 decreased in untreated SAA patients
      (0.16(0.02-0.29)) and over-expressed in recovering patients (1.17(0.82-1.86), P <
      0.05). The mRNA expression of RAP1 was significantly higher in untreated patients
      (4.14 (1.93-6.92)) than that in recovering group (0.87 (0.30-1.73) ) and controls
      (0.62 (0.45-4.07) , both P < 0.05). CONCLUSION: Changes in telomere length and
      shelterin gene expression occur in CD3(+)T cells of SAA patients and may be
      correlated with disease severity.

PMID- 24028720
TI  - [Clinical features of adult patients with Eisenmenger syndrome associated with
      different types of congenital heart disease].
AB  - OBJECTIVE: To explore the clinical features and hemodynamics of adult patients
      with Eisenmenger syndrome in different types of congenital heart diseases (CHD).
      METHODS: Patients with Eisenmenger syndrome with different types of CHD diagnosed
      by right heart catheterization were enrolled from 31 clinical centers in China
      during the period from May 2007 to October 2010. Age, gender, body mass index
      (BMI), symptoms and signs, World Health Organization functional class (WHO-FC) of
      pulmonary hypertension, six-minute walk distance (6MWD) and hemodynamics were
      recorded. All the above indices were analyzed and compared. RESULTS: A total of
      224 patients with Eisenmenger syndrome with 3 kinds of CHD were enrolled,
      including atrial septal defect (n = 67), ventricular septal defect (n = 104) and
      patent ductus arteriosus (n = 53). Among them, there were 67 males (29.9%) and
      157 females (70.1%) with a mean age of (29.6 +/- 9.9) years (range: 15-63). Mean
      BMI was (19.9 +/- 4.0) kg/m(2) and mean 6MWD (371 +/- 75) m. The majority of
      patients were in WHO-FC II (n = 158, 70.5%) and III (n = 64, 28.6%).
      Electrocardiogram of 77.2% of them indicated hypertrophic right ventricle. Mean
      right atrial pressure was (8.9 +/- 5.7) mm Hg (1 mm Hg = 0.133 kPa), mean
      pulmonary arterial pressure (mPAP) (77.2 +/- 19.1) mm Hg, cardiac index (3.03 +/-
      1.35) L.min(-1) . m(-2) and pulmonary vascular resistance (PVR) (1621 +/- 887)
      dyn . s . cm(-5). CONCLUSIONS: The majority of patients with Eisenmenger syndrome
      with different types of CHD are young females and ventricular septal defect is
      the most frequent underlying cause. The deterioration of heart function in
      patients with Eisenmenger syndrome is non-parallel to mPAP and PVR in CHD.

PMID- 24028719
TI  - [Inhibitory effects of tacrolimus on effector T cells from patients with severe
      aplastic anemia].
AB  - OBJECTIVE: To explore the inhibitory effects of tacrolimus (FK506) on effector T
      cells in vitro and examine the relationship between effector T cells and clinical
      features in patients with severe aplastic anemia (SAA) to elucidate its immune
      mechanism. METHODS: The CD8(+) HLA-DR(+) cells, sorted by immunomagnetic
      separation from bone marrow mononuclear cells (BMMNC) of 16 SAA patients, were
      cultured in different concentrations of interleukin-2 (IL-2) alone or with FK506
      for 72 hours. The proliferation effect was measured with methyl thiazolyl
      tetrazolium (MTT) method. The T lymphocytes were sorted from the SAA patients by
      lymphocyte separation medium and cultured alone or with IL-2 or with FK506 or
      FK506 plus cyclosporin A (CsA) for 18 hours. The expression of tumor necrosis
      factor-beta (TNF-beta) in CD8(+) HLA-DR(+) T cells was analyzed by flow
      cytometry. The relationship between the expression of TNF-beta and the clinical
      data, including percentages of reticulocyte and lymphocytes in peripheral blood
      cell count and ratio of CD4(+) T cells and CD8(+)T cells, was also analyzed.
      RESULTS: At the concentration of IL-2 greater than or equal to 20 U/ml, the cell
      proliferation (A values, 0.538 +/- 0.142) were significantly higher than that in
      the blank culture hole (0.505 +/- 0.153) (P < 0.05). The A values significantly
      decreased (0.386 +/- 0.124) after the addition of FK506 (P < 0.05). Compared with
      control group, the expression of TNF-beta was significantly higher in IL-2 group
      (73.36% +/- 16.73% vs 66.61% +/- 16.20%, P < 0.05), significantly lower in FK506
      and FK506 plus CsA groups (P < 0.05). No significant differences existed between
      the FK506 and FK506 plus CsA groups (47.78% +/- 20.09% and 42.23% +/- 21.35%, P >
      0.05). The expression of TNF-beta in SAA was negatively correlated with the
      percentage of reticulocyte and the ratio of CD4(+) T cell and CD8(+) T cell,
      positively correlated with the percentage of lymphocyte in peripheral blood count
      (r = -0.86, -0.90, 0.77, all P < 0.05). CONCLUSIONS: IL-2 can enhance the
      proliferation and expression of TNF-beta of CD8(+)HLA-DR(+)T cells from SAA
      patients. Such an effect is inhibited by FK506. And FK506 and FK506 plus CsA have
      similar effects.

PMID- 24028721
TI  - [Clinicopathological significance of abnormal metabolism of polyunsaturated fatty
      acids in colorectal cancer tissue].
AB  - OBJECTIVE: To explore the relationship between different tissue levels of
      polyunsaturated fatty acid (PUFA) and the clinicopathologic parameters in
      colorectal carcinoma (CRC) and evaluate their prognostic significance. METHODS:
      Fresh frozen malignant tissue was obtained from 82 colorectal cancer patients at
      PLA general Hospital from December 2010 to March 2011. The immunohistochemical
      results were obtained for vascular endothelial growth factor (VEGF), P53 and Ki
      67. The relationship between the PUFA level and such clinicopathological profiles
      as age, gender, location, differentiation degree, TNM (tumor, node and
      metastasis) stage, VEGF, Ki-67 and P53 was analyzed. RESULTS: Tissue level of
      arachidonic acid (AA) in patients aged over 60 years (n = 44) was significantly
      lower than those under 60 years (n = 38) (0.12% +/- 0.06% vs 0.17% +/- 0.09%, P =
      0.045). In patients with tumor size < 5 cm (n = 42), tissue level of EPA was
      significantly higher (0.29% +/- 0.13% vs 0.20% +/- 0.14%, P = 0.030) while omega
      6/omega-3 PUFA lower (10.8 +/- 2.6 vs 13.2 +/- 6.4, P = 0.031). Significant
      statistical difference existed in tissue level of LA, AA/omega-3 PUFA in
      different differentiation degrees(P = 0.013, 0.027). Tissue level of linoleic
      acid(LA) in poorly differentiated tumor was the highest (19.9% +/- 6.3%) while
      AA/omega-3 PUFA the lowest (4.1 +/- 2.0, P < 0.05). Tissue level of LA was higher
      in VEGF-positive tumors than those in VEGF-negative counterparts(16.2% +/- 3.7%
      vs 13.9% +/- 2.7%, P = 0.009) while the ratios AA/omega-3 PUFA, AA/omega-6 PUFA,
      AA/LA in VEGF-positive tumors were lower than those in VEGF-negative counterparts
      (5.0 +/- 1.8 vs 6.7 +/- 3.3, 0.30 +/- 0.09 vs 0.34 +/- 0.09, 0.50 +/- 0.21 vs
      0.61 +/- 0.21, P = 0.004, 0.038, 0.030) . In Ki-67 negative LA was highest (22.5%
      +/- 10.1%, P = 0.048). No significant differences existed in the level of PUFA
      among the gender, the clinicopathological stage, lymph node metastasis and groups
      with differential expressions of P53 (all P > 0.05). CONCLUSIONS: The tissue
      levels of PUFA are somewhat correlated with the clinicopathologic parameters of
      CRC. And the prognosis of CRC may be evaluated through the test of PUFA.

PMID- 24028722
TI  - [Mathematical cognitive function in children with attention deficit hyperactivity
      disorder: a behavior and event-related potential study].
AB  - OBJECTIVE: To explore the mathematics cognitive function of children with
      attention deficit hyperactivity disorder and explore neural mechanisms with event
      related potential(ERP) and behaviors. METHODS: Behavior data and ERP elicited by
      performing mental calculation tasks were recorded in 27 children with ADHD and 29
      normal controls from July to October 2012 at Third Affiliated Hospital of Soochow
      University.The differences of behaviors and N2 component of ERP were compared and
      analyzed. RESULTS: The reaction time of the children with ADHD were longer than
      the control group in addition, subtraction and multiplication ((949 +/- 144) vs
      (829 +/- 166) ms, (981 +/- 129) vs (856 +/- 170) ms, (944 +/- 136) vs (825 +/-
      172) ms, all P < 0.05). While the correct rate were less than normal control in
      all three arithmetic operations (0.80% (0.72%, 0.88%) vs 0.90% (0.85%,0.96%),
      0.78% (0.64%,0.85%) vs 0.90% (0.84%,0.93%), 0.86% (0.74%,0.92%) vs
      0.93%(0.90%,0.98%), all P < 0.05). N2 component could be elicited by all subjects
      in forehead. The amplitude of N2 of children with ADHD were significantly lower
      than control group in all three arithmetic operations at left frontal (F3: (-3.5
      +/- 5.2) vs (-6.7 +/- 3.5)uV, (-3.8 +/- 4.0) vs (-7.4 +/- 4.5)uV, -5.8 (-7.6,1.6)
      vs -6.4(-10.3, -4.9) uV, all P < 0.05) and Fz ((-4.3 +/- 6.4) vs ( -7.4 +/- 4.2)
      uV, (-5.0 +/- 5.4) vs (-7.9 +/- 4.6)uV, -5.2(-9.7, -0.6) vs -7.9 (-10.5, -5.1)uV,
      all P < 0.05), the latency of ADHD group were prolonger than controls in
      subtraction operations at right and left frontal ((328 +/- 36) vs (307 +/- 27)ms,
      325 (307,354)vs 309 (280, 330)ms) and frontal electrodes ((331 +/- 35) vs (311 +/
      30) ms, all P < 0.05). In addition and multiplication operations, there was no
      significant difference in latency (all P > 0.05). CONCLUSIONS: The children with
      ADHD have weak capacities of inhibition irrelevant information and paying
      attention to control. Their deficits in mental arithmetics may be due to the
      difficulties of selecting the best strategy during cognitive tasks.

PMID- 24028723
TI  - [Expression and significance of IFN-gamma and IL-4 in the effusion and peripheral
      blood of chronic otitis media with effusion patients].
AB  - OBJECTIVE: To explore the shift of Th2/Th1 type cytokine profiles in middle ear
      and peripheral blood of chronic otitis media with effusion (COME) patients.
      METHODS: Middle ear effusions (MEEs) and peripheral bloods were collected from 30
      COME patients between April 2011 and July 2012 at Department of Otolaryngology,
      Beijing Tongren Hospital, Capital Medical University. Peripheral blood samples
      were collected from 20 healthy controls. The expressions of IFN-gamma (Th1
      cytokine) and IL-4 (Th2 cytokine) in peripheral blood and middle ear fluid were
      assessed by flow cytometry and cytometric bead array. The expression levels of
      cytokines in peripheral blood were compared between patient and control groups.
      Moreover, the levels of cytokines in the Middle ear fluid and the supernatant of
      COME patients were also compared. RESULTS: Compared to the control group, the
      level of IL-4 in peripheral blood of COME patients significantly increased (0.7%
      +/- 0.8% vs 2.4% +/- 4.5%, P < 0.05) . The ratio of IFN-gamma positive cells/IL-4
      positive cells was significantly lower in peripheral blood of COME patients than
      that of control group (17 +/- 13 vs 35 +/- 19, P < 0.05) . However, the level of
      IFN-gamma showed no significant difference between two groups (12% +/- 8% vs 13%
      +/- 8%, P > 0.05) . The levels of IL-4 and IFN-gamma in middle ear fluid and the
      supernatant of the case group showed no significant difference. CONCLUSIONS: COME
      may be a Th2 predominant disease. Th1/Th2 imbalance is probably involved in the
      pathogenesis of COME. The role of the allergic reaction in middle ear
      microenvironment remains uncertain.

PMID- 24028724
TI  - [Diagnostic value of endobronchial ultrasound-guided transbronchial needle
      aspiration in paratracheal mediastinal lesions].
AB  - OBJECTIVE: To explore the diagnostic value of endobronchial ultrasound-guided
      transbronchial needle aspiration (EBUS-TBNA) in diagnosing mediastinal lesions.
      METHODS: A total of 264 patients with mediastinal lesions on chest CT at
      Provincial Hospital Affiliated to Shandong University between January 2010 and
      April 2012 were retrospectively enrolled. Their cytopathological results were
      difficult to be assessed by conventional bronchoscopy. There were 222 cases whose
      lymph nodes long axis was >1.5 cm. Among them, 174 cases underwent TBNA alone
      (group A) and the other 48 cases EBUS-TBNA alone (group B). The remaining 42
      cases whose lymph nodes long axis was <1.5 cm belonged to group C and underwent
      TBNA (group C1) and EBUS-TBNA (group C2) sequentially as a combined procedure.
      The associations of pathologic examinations, diagnostic positive rate and
      complications were analyzed. RESULTS: Among 174 cases in group A, 154 cases were
      diagnosed with a positive diagnostic rate of 88.5%. There were 135 malignant
      lesions while 19 cases were diagnosed with benign diseases and 5 cases had
      accidental vascular injury. Among 48 cases in group B, 45 cases were diagnosed
      with a positive diagnostic rate of 93.8%. There were 33 malignant lesions while
      12 cases were diagnosed with benign diseases. Among 42 patients in group C1, 31
      cases were diagnosed by TBNA with a positive diagnostic rate of 73.8%. There were
      23 malignant lesions while 8 cases were diagnosed with benign diseases and 2
      cases had accidental vascular injury. Among 42 patients in group C2, 39 cases
      were diagnosed with a positive diagnostic rate of 92.8%. There were 30 malignant
      lesions while 9 cases had benign diseases. No difference existed in diagnostic
      positive rate between groups A and B (chi(2) = 0.621, P = 0.431) while the
      diagnostic positive rate in group A was much higher than group C1 (chi(2) =
      5.945, P = 0.015). The difference between groups B and C2 was insignificant
      (chi(2) = 0.065, P = 0.320) while there was significant difference between groups
      C1 and C2 (chi(2) = 5.486, P = 0.019). CONCLUSION: With a low complication rate,
      EBUS-TBNA can yield a higher diagnostic positive rate in diagnosing small
      mediastinal diseases than conventional TBNA.

PMID- 24028725
TI  - [Clinical characteristics and prognosis of infantile-onset glycogen storage
      disease type II in 16 Chinese patients].
AB  - OBJECTIVE: To explore the clinical characteristics and prognosis of infantile
      onset glycogen storage disease type II (GSDII) in Chinese patients. METHODS:
      Sixteen children diagnosed as infantile-onset GSDII in Shanghai Children's
      Medical Center during Jan 2005 to Dec 2012 were recruited. Their disease history,
      presenting symptom, physical signs, biochemical tests and examinations of
      electrocardiogram and echocardiography were analyzed retrospectively. Follow-up
      data on motor development and survival were also collected and analyzed
      retrospectively. RESULTS: 16 cases were diagnosed as infantile-onset GSDII (10
      males, 6 females), in which the peripheral blood levels of acidic alpha
      glucosidase were remarkably low or completely absent. All of them were
      complicated with cardiac hypertrophy and left ventricular mass index was 161-616
      g/m(2). Severe muscular weakness, hypotonia and development lag were found in all
      during the follow-up. Creatine kinase was detected in 15 patients and its level
      became significantly elevated in 14 of them. Alanine aminotransferase and
      aspartate aminotransferase were detected in 15 patients and their levels became
      significantly elevated in all of them. The median age was 3.6 (2.0-6.8) months at
      symptom onset and 6.5 (3.8-9.3) months at diagnosis. And 14 of them died during
      the follow-up and the median age at death was 9.0 (4.7-18.7) months. CONCLUSIONS:
      As a fatal disease, infantile-onset GSDIIhas the prominent clinical
      manifestations of progressive cardiac hypertrophy and muscular weakness or
      hypotonia. The clinical features and nature history of Chinese patients are
      similar as those reported in other countries. Detection of acidic alpha
      glucosidase activity in peripheral blood is an effective way of screening for
      infantile-onset GSDII.

PMID- 24028726
TI  - [Analysis of correlation between breast cancer molecular subtypes and prognosis
      of patients receiving breast-conserving therapy].
AB  - OBJECTIVE: To evaluate the effects of molecular subtypes on the prognosis of
      breast cancer patients after BCT (breast-conserving therapy). METHODS: From
      January 1999 to December 2007, a total of 699 female patients on BCT were
      analyzed retrospectively. They were grouped according to the results of
      immunohistochemistry, they were grouped as Luminal A (ER+/PR+/HER2-, Ki-67 <
      14%), Luminal B (ER+/PR+/HER2 +/- , Ki-67 > 14%), HER2 (ER-/PR-/HER2+) and triple
      negative breast cancer (TNBC) (ER-/PR-/HER2-). RESULTS: Among them, the
      recurrence rate, metastasis rate and survival rate within 5 years after BCT
      accounted for 6.0%, 6.0% and 91.8% respectively. There were statistical
      differences in metastasis rate and survival rate among patients with different
      molecular subtypes (P < 0.001), lymph node status (P < 0.001) and on chemotherapy
      or not (P < 0.001) on multivariate analysis. Though, on univariate analysis,
      different molecular subtypes had different risks for local failure (P = 0.022).
      On multivariate analysis, this difference was not statistically significant (P =
      0.081). CONCLUSION: Despite a worse prognosis of TNBC versus other subtypes, BCT
      is a viable option for selected TNBC patients.

PMID- 24028727
TI  - [Clinical and prognostic analyses of juvenile sudden sensorineural hearing loss].
AB  - OBJECTIVE: To explore the clinical profiles of juvenile sudden sensorineural
      hearing loss (JSSNHL) and examine its clinical characteristics and prognosis.
      METHODS: A retrospective review was conducted for the clinical symptoms,
      audiological characteristics, hematological indices and prognosis in JSSNHL
      during the past 2 years (from June 2008 to November 2010). All patients were
      divided into 2 groups according to age, that is group childhood (A, 0-12 years
      old) and group adolescence (B, 13-18 years old). RESULTS: JSSNHL patients were
      rarely associated with "aural fullness" symptoms. Two groups of patients with
      "tinnitus" symptom accounted for 88.2% and 89.5%. Those with "vertigo" symptom
      accounted for 47.1% and 44.4% respectively. Most patients (81.6%) showed severe
      and profound hearing loss. The most common types of audiometric curve were flat
      and total deafness. Some obvious differences existed between two groups in
      hematological indices, such as platelet count, concentrations of electrolyte
      ions, mean corpuscular volume and mean corpuscular hemoglobin. Almost half of
      them (42.1%) improved hearing level during systemic medical treatment. The
      patients of two groups showed no significant difference in efficacies. And the
      hearing enhancement degree of patients in group B was more apparent than that of
      group A. CONCLUSIONS: JSSNHL has different clinical features in different age
      groups. And the outcomes of personalized treatment regimens may be further
      improved through classification and grading.

PMID- 24028728
TI  - [Transperitoneal laparoscopic ureterolithotomy for upper ureteral calculi: a
      report of 1171 cases].
AB  - OBJECTIVE: To evaluate clinical outcomes and values of transperitoneal
      laparoscopic ureterolithotomy. METHODS: A total of 1171 patients with upper
      ureteral calculi were recruited during September 1999 to February 2012. The
      etiologies included impacted calculi (n = 1100), non-impacted calculi (n = 71),
      multiple ureteral calculi (n = 51) and combined small calculi in unilateral
      kidney (n = 139). Maximum diameter of calculi was 1.5 (0.8-2.6) cm. All patients
      underwent transperitoneal laparoscopic ureterolithotomy and double J stent was
      implanted intraoperatively. RESULTS: Two cases were converted into open
      operation. Calculi moving up into pelvis occurred in 27 cases. And 25 cases
      converted into laparoscopic pyelolithotomy and stones were removed successfully.
      Two cases received extra extracorporeal shock wave lithotripsy postoperatively.
      The remaining 1142 cases were treated successfully with an operative duration of
      56.1 (26-160) min and an estimated volume of blood loss at 45.2 (10-250) ml. The
      period of drainage tube was 3.1 (1-7) days. Postoperative hospitalization stay
      was 4.8 (3-9) days. One patient suffered urine leakage and healed at Day 6 days
      post-operation. Ten cases suffered D-J stent bladder non-arrival or retraction
      and double J stents were extracted by ureteroscopy. One case suffered paralytic
      ileus and recovered 7 days later. Another case suffered severe hematuria. No
      intestine or adjacent viscera injury was observed. The follow-up period of 827
      cases was 7.3 (24-108) months. Among 12 cases of ureteral stricture, ureteral
      dilation (n = 7) and ureteral anastomosis (n = 3) were performed. For 5 cases of
      renal atrophy, 3 underwent nephrectomy because of recurrent lumbago or persistent
      urinary infection. CONCLUSIONS: Transperitoneal laparoscopic ureterolithotomy has
      the advantages of minimal morbidity, little postoperative discomfort and high
      stone clearance rate over open surgery. It should be widely adopted for the
      patients with upper ureteral impacted calculi.

PMID- 24028729
TI  - [Management experience of acute renal failure induced by unilateral ureteral
      calculi obstruction].
AB  - OBJECTIVE: To explore the causes and treatment options of acute renal failure
      induced by unilateral ureteral calculi obstruction. METHODS: The clinical data of
      12 cases of acute renal failure induced by unilateral ureteral calculi
      obstruction between August 2008 and July 2012 were reviewed retrospectively.
      There were 5 males and 7 females with an average age of 65.7 years. Their
      clinical data and treatment options were retrospectively analyzed and summarized.
      Seven cases showed right side ureteral calculus with hydronephrosis while another
      5 presented left side ureteral calculus with hydronephrosis. Serum creatinine was
      higher than 310 umol/L in 12 cases. Anuria appeared in 4 cases for 1-7 days while
      oliguria in 8 cases for 2-10 days. High fever was present in 11 cases, the
      highest of whom was 40  degrees C. White blood cell count increased in 10 cases
      (>10*10(9)/L) and decreased in 2 cases (<4 * 10(9)/L). RESULTS: The therapeutic
      options included insertion of double J stent for internal drainage (n = 1),
      percutaneous nephrostomy for external drainage (n = 10) and open operation (n =
      1). Traditional treatments were performed to manage ureteral calculus in the
      above 11 cases with drainage. All cases had improved renal function after
      comprehensive treatment of anti-infection, antishock, rinsing stones and
      relieving obstruction. All 12 cases were treated successfully. CONCLUSIONS:
      Unilateral ureteral calculus may impair contralateral renal function and cause
      acute renal failure due to the absorption of toxin at obstructive side. The keys
      of management are eliminating toxin and relieving obstruction.

PMID- 24028730
TI  - [Subsequent retroperitoneoscopy for patients with previous ipsilateral
      retroperitoneal surgery].
AB  - OBJECTIVE: To evaluate the feasibility and clinical results of subsequent
      retroperitoneoscopic surgery for patients with previous ipsilateral
      retroperitoneal surgery through frank incision. METHODS: A total of 10 patents
      were selected for subsequent laparoscopic surgery through retroperitoneal
      approach. Among them, there were recurrent renal cysts (n = 4) including a
      history of open surgery (n = 1) and retroperitoneal surgery (n = 3) and
      nonfunctional kidneys (n = 6) including open nephropyelopolasty (n = 3),
      retroperitoneoscopic nephropyelopolasty (n = 1) and retroperitoneoscopic
      ureterolithotomy (n = 2). The mean surgical duration was (12-85) 38.6 months. All
      patients underwent retroperitoneoscopy. Decortication was performed for renal
      cysts and nephrectomy for nonfunctional kidneys. RESULTS: All operations were
      successfully performed with a mean surgical duration of 97 (40-185) minutes and a
      mean volume of blood loss 125 (20-460) ml. Among 4 cases with intraoperative
      peritoneal rupture, one case had renal cyst on ventral side. After enlargement,
      the procedure was performed through peritoneal cavity. The mean postoperative
      hospital stay was 5.6 (3-9) days. Nine patients received a mean follow-up period
      of 21.5 (3-47) months. All symptoms were relieved without any occurrence of
      postoperative complications. CONCLUSION: For patients with previous ipsilateral
      retroperitoneal surgery, retroperitoneoscopy may be feasible for properly
      selected cases.

PMID- 24028731
TI  - [Anti-fibrotic effects of angiotensin1-7 on bleomycin-induced pulmonary fibrosis
      in rats].
AB  - OBJECTIVE: To explore the anti-fibrotic effects of angiotensin (Ang) 1-7 on
      bleomycin (BLM) -induced pulmonary fibrosis in rats. METHODS: Eighteen Wistar
      male rats were randomly divided into 3 groups, including control group
      (intratracheal instillation with physiological saline and subcutaneous micro-pump
      with bi-distilled water at the rate of 0.29 ul/h), BLM group (intratracheal
      instillation with bleomycin and subcutaneous micro-pump with bi-distilled water
      at the same rate) and BLM+Ang1-7 group (intratracheal instillation with bleomycin
      and subcutaneous micro-pump with Ang1-7 at a dose of 25 ug.kg(-1) . h(-1) at the
      same rate). At Day 28, lung tissues were collected. Histological changes of lungs
      were evaluated by hematoxylin and eosin and Masson's trichrome stains. Collagen
      content of lung tissues was assessed by hydroxyprolin concentration. Then the
      products of protein and RNA were collected. And Western blot and realtime
      polymerase chain reaction (RT-PCR) were used to detect the protein or mRNA of TGF
      beta1 and alpha-collagenI. Human embryonic lung fibroblast (HFL-1) was divided
      into 5 groups: (1) control group: no stimulation; (2) AngII group: stimulation of
      AngII (10(-7)mol/L) ; (3) Ang1-7 group: stimulation of Ang1-7 (10(-7)mol/L); (4)
      Ang1-7 plus AngII group: stimulation by AngII (10(-7)mol/L) with Ang1-7 (10(
      7)mol/L) pre-treatment; (5) Ang1-7+AngII+A-779 group: stimulation by AngII and
      Ang1-7 (10(-7) mol/L) with Mas receptor inhibitor A-779 (10(-6)mol/L) pre
      treatment. Then the products of protein and RNA were collected. And QuantiGene
      and RT-PCR were used to detect the activation of TGF-beta1, and alpha-collagenI
      mRNA. RESULTS: Compared with control group, fibrosis score and hydroxyproline
      concentrations increased significantly in BLM group, but declined in BLM+Ang1-7
      group. The difference was statistically significant (P < 0.05). TGF-beta1 mRNA,
      alpha-collagenI mRNA and alpha-collagenI protein level were up-regulated by BLM
      (4.45 +/- 0.45 vs 1.00 +/- 0.20, 5.14 +/- 0.55 vs 1.00 +/- 0.08, 1.48 +/- 0.34 vs
      0.23 +/- 0.11) (all P < 0.05); while compared with BLM group, those of BLM+Ang1-7
      group were down-regulated (2.80 +/- 0.35, 3.10 +/- 0.52, 0.49 +/- 0.11) (all P <
      0.05). In vitro: TGF-beta1 mRNA and alpha-collagen I mRNA level were up-regulated
      by AngII (1.67 +/- 0.26 vs 1.00 +/- 0.10, 4.86 +/- 1.36 vs 1.46 +/- 0.54) (all P
      < 0.05); while those of AngII+Ang1-7 group were down-regulated (0.91 +/- 0.30,
      1.57 +/- 0.27) compared with AngII group (all P < 0.05); no significant
      difference existed between the AngII+Ang1-7+A-779 group (1.25 +/- 0.14, 1.29 +/-
      0.49) and AngII+Ang1-7 group (P > 0.05). CONCLUSION: Ang1-7 has anti-fibrous
      effect upon bleomycin-induced pulmonary fibrosis in rats and such an effect of
      Ang1-7 may be associated with AngII-induced expression of TGF-beta1.

PMID- 24028732
TI  - [Adenovirus-mediated combined gene therapy of interleukin-18 and interleukin-12
      for prostate cancer: an experimental study].
AB  - OBJECTIVE: To explore the therapeutic regimens of metastatic prostate cancer so
      as to provide the experimental rationales for its gene therapy. METHODS: The
      adenoviral vectors expressing cytokines interleukin-18 (IL-18) and interleukin-12
      (IL-12) were used to induce tumor regression in a C57BL/6 murine model of
      prostate cancer (n = 110). RESULTS: Adenoviral vectors could express IL-18 and IL
      12 effectively. The rates of tumorigenesis were 10/10, 10/10, 4/10, 5/10 and
      2/10, the durations of tumor growth (12.3 +/- 1.5), (12.8 +/- 1.0), (15.4 +/-
      1.3), (14.8 +/- 0.8), (24.5 +/- 2.2) days and the diameters of tumor nodule after
      inoculation 30 days (37.0 +/- 3.0), (35.0 +/- 4.6), (25.0 +/- 2.0), (27.0 +/-
      4.1) and (9.5 +/- 3.2) mm respectively in inoculation wild-type, AdLacZ, AdmIL
      18, AdhIL-12, AdmIL-18 and AdhIL-12 of RM-1 cell. Compared to the other four
      groups, AdmIL-18 and AdhIL-12 developed smaller and delayed tumors (P < 0.01).
      Intratumoral injection of Adm IL-18 and AdhIL-12 could not only regress the
      established tumors, but also reduce the number of distal lung metastases (P <
      0.01). CONCLUSION: Adenovirus-mediated delivery of IL-18 and IL-12 locally by
      intratumoral injection is highly effective in inducing specific antitumor immune
      responses.

PMID- 24028733
TI  - Local and systemic innate immune response to secondary human peritonitis.
AB  - INTRODUCTION: Our aim was to describe inflammatory cytokines response in the
      peritoneum and plasma of patients with peritonitis. We also tested the hypothesis
      that scenarios associated with worse outcome would result in different cytokine
      release patterns. Therefore, we compared cytokine responses according to the
      occurrence of septic shock, mortality, type of peritonitis and peritoneal
      microbiology. METHODS: Peritoneal and plasma cytokines (interleukin (IL) 1, tumor
      necrosis factor alpha (TNFalpha), IL-6, IL-10, and interferon gamma (IFNgamma))
      were measured in 66 patients with secondary peritonitis. RESULTS: The
      concentration ratio between peritoneal fluid and plasma cytokines varied from 5
      (2 to 21) (IFNgamma) to 1310 (145 to 3888) (IL-1). There was no correlation
      between plasma and peritoneal fluid concentration of any cytokine. In the plasma,
      TNFalpha, IL-6, IFNgamma and IL-10 were higher in patients with shock versus no
      shock and in nonsurvivors versus survivors (P <=0.03). There was no differential
      plasma release for any cytokine between community-acquired and postoperative
      peritonitis. The presence of anaerobes or Enterococcus species in peritoneal
      fluid was associated with higher plasma TNFalpha: 50 (37 to 106) versus 38 (29 to
      66) and 45 (36 to 87) versus 39 (27 to 67) pg/ml, respectively (P = 0.02). In the
      peritoneal compartment, occurrence of shock did not result in any difference in
      peritoneal cytokines. Peritoneal IL-10 was higher in patients who survived (1505
      (450 to 3130) versus 102 (9 to 710) pg/ml; P = 0.04). The presence of anaerobes
      and Enterococcus species was associated with higher peritoneal IFNgamma: 2 (1 to
      6) versus 10 (5 to 28) and 7 (2 to 39) versus 2 (1 to 6), P = 0.01 and 0.05,
      respectively). CONCLUSIONS: Peritonitis triggers an acute systemic and peritoneal
      innate immune response with a simultaneous release of pro and anti-inflammatory
      cytokines. Higher levels of all cytokines were observed in the plasma of patients
      with the most severe conditions (shock, non-survivors), but this difference was
      not reflected in their peritoneal fluid. There was always a large gradient in
      cytokine concentration between peritoneal and plasma compartments highlighting
      the importance of compartmentalization of innate immune response in peritonitis.

PMID- 24028734
TI  - Incidence of pregnancy-related discomforts and management approaches to relieve
      them among pregnant women.
AB  - AIMS AND OBJECTIVES: To determine the incidence of pregnancy-related physical
      symptoms in healthy pregnant women and their management strategies. BACKGROUND:
      In normal progression of pregnancy, many symptoms were experienced. Pregnancy
      related physical symptoms may have a negative effect on pregnant women's quality
      of life. However, pregnant women avoid taking medications from the fear that the
      medication they use may have a harmful effect on the foetus. Therefore, they
      practise nonpharmacological methods to help them manage their pregnancy-related
      physical symptoms. DESIGN: This study used a comparative and descriptive design.
      METHODS: The study population comprised of pregnant women who were visiting for
      routine check-up and/or examination in the obstetrics gynaecology outpatient
      clinics of three hospitals in Erzurum, Turkey. The data were collected via a
      questionnaire including socio-demographic items and questions to identify the
      pregnancy-related physical symptoms that they experienced and their management
      strategies. RESULTS: The top three most reported complaints were nausea-vomiting
      (87.8%), fatigue (77.9%) and breast pain-tenderness (76.2%) during the first
      trimester, whereas polyuria (79.9%, 88.4%), fatigue (75.6%, 88.4%) and heart burn
      (71.3%, 81.8%) during the second and third trimesters. Depending on the symptoms,
      the pregnant women either did nothing or took correct, incorrect or empirical
      actions to manage their problems. Data revealed that the major source of
      knowledge was based on their previous experience and that of close relatives. As
      their education level increased, the percentage of women taking scientifically
      proven action to correct the problem increased. CONCLUSIONS: Various physical
      symptoms were experienced by women in each trimester of pregnancy. The majority
      of the women did not do anything to alleviate their physical symptoms. RELEVANCE
      TO CLINICAL PRACTICE: Midwives and nurses should question the strategies used by
      pregnant women. In this way, the inappropriate and incorrect practices can be
      determined, and education on the appropriate practices can be provided.

PMID- 24028735
TI  - Birth cohort testing for hepatitis C virus: implications for clinical social
      workers in health care settings.
AB  - The Centers for Disease Control and Prevention recommends one-time hepatitis C
      virus (HCV) testing for baby boomers born between 1945-1965 in the United States.
      This public health initiative is known as birth cohort (baby boomer) testing for
      HCV. The intent of birth cohort testing is to identify and mobilize undiagnosed
      HCV-infected persons into care and treatment. Subsequently, clinical social
      workers in health care settings can anticipate a substantial increase in the
      number of HCV-infected persons presenting for care and treatment. The purpose of
      this article is to inform clinical social workers in health care settings of HCV,
      the standard of care and treatment for HCV, and clinical dilemmas associated with
      HCV patient care. Epidemiology and natural history of HCV, the standard of care
      and treatment for HCV, and etiology and management of neuropsychiatric adverse
      effects associated with patient care are discussed. 

PMID- 24028736
TI  - HIV stigma and discrimination in medical settings: stories from African women in
      New Zealand.
AB  - Recent changes in New Zealand's HIV and immigration situations have sparked a
      need to understand the experiences of HIV-positive African newcomers there. Here
      a narrative lens was brought to a previous qualitative study to harvest stories
      about discrimination in medical settings in New Zealand, told by four HIV
      positive African women. Despite describing positive experiences with specialist
      HIV providers, their accounts shed light on weaknesses within the health care
      system regarding the rights and treatment of immigrants living with HIV.
      Participants reported inappropriate use of universal precautions, violations of
      confidentiality rights, discriminatory comments about Africans or persons with
      HIV, and misinformation about HIV transmission. Interventions must include
      enforcement of The Privacy Law and consistent training and monitoring of employee
      behavior in health care organizations. 

PMID- 24028737
TI  - Implementation of health and mental health evidence-based practices in safety net
      settings.
AB  - Implementation of evidence-based practices (EBP) in health and mental health
      settings has not been as successful as anticipated. Patients in safety net
      settings have even less opportunity to receive evidence-based care. Translation
      research has been dominated by efficacy trials, which often do not translate to
      the complexity of safety net settings. Implementation research to date seems to
      focus mostly on provider and organizational contextual factors more than macro
      and patient factors crucial to outcomes in safety net settings. Focus on
      translation and adaptation of interventions to safety net settings, and use of
      qualitative methods to flesh out complex processes and involve more stakeholders
      will help give safety net patients access to state of the art care. This issue is
      important for social workers to understand due to their ethical obligation to
      advocate for social justice and access to care for vulnerable and oppressed
      populations. 

PMID- 24028738
TI  - Mild traumatic brain injury: a place for social work.
AB  - Mild traumatic brain injury (mTBI) has emerged as a significant public health
      issue. Increases in both the prevalence and awareness of this injury have
      resulted in a greater demand for mTBI-informed care. Our exploratory, qualitative
      study examines the work lives of front-line mTBI professionals. Findings suggest
      that mTBI rehabilitation work often requires substantial emotional energy given
      the impact that injury-related issues have on professionals' therapeutic work
      with clients. We suggest that social work, with a focus on the psychosocial
      implications of injury and recovery, is well-positioned to take a larger role in
      mTBI care and rehabilitation. 

PMID- 24028739
TI  - Professional competencies and training needs of professional social workers in
      integrated behavioral health in primary care.
AB  - The Affordable Care Act has led to a widespread movement to integrate behavioral
      health services into primary care settings. Integrated behavioral health (IBH)
      holds promise for treating mild to moderate psychiatric disorders in a manner
      that more fully addresses the biopsychosocial spectrum of needs of individuals
      and families in primary care, and for reducing disparities in accessing
      behavioral health care. For behavioral health practitioners, IBH requires a shift
      to a brief, outcome-driven, and team-based model of care. Despite the fact that
      social workers comprise the majority of behavioral health providers in IBH
      settings, little research has been done to assess the extent to which social
      workers are prepared for effective practice in fast-paced primary care. We
      conducted a survey of social workers (N = 84) in IBH settings to assess the
      following: (1) Key competency areas for social work practice in IBH settings and
      (2) Self-rated preparedness for effective practice in IBH settings. Online
      snowball sampling methods were used over a period of 1 month. Results indicate
      that social workers feel prepared for general practice in IBH settings, but would
      benefit from additional training in IBH-specific competency areas identified in
      the survey. Findings can help guide social work training to improve workforce
      preparedness for practice in IBH settings in the wake of health care reform. 

PMID- 24028740
TI  - Reference loci for RT-qPCR analysis of differentiating human embryonic stem
      cells.
AB  - BACKGROUND: Selecting stably expressed reference genes is essential for proper
      reverse transcription quantitative polymerase chain reaction gene expression
      analysis. However, this choice is not always straightforward. In the case of
      differentiating human embryonic stem (hES) cells, differentiation itself
      introduces changes whereby reference gene stability may be influenced. RESULTS:
      In this study, we evaluated the stability of various references during retinoic
      acid-induced (2 microM) differentiation of hES cells. Out of 12 candidate
      references, beta-2-microglobulin, ribosomal protein L13A and Alu repeats are
      found to be the most stable for this experimental set-up. CONCLUSIONS: Our
      results show that some of the commonly used reference genes are actually not
      amongst the most stable loci during hES cell differentiation promoted by retinoic
      acid. Moreover, a novel normalization strategy based on expressed Alu repeats is
      validated for use in hES cell experiments.

PMID- 24028741
TI  - The lynx effect?

PMID- 24028742
TI  - Outcome of occupational electrical injuries among French electric company
      workers: a retrospective report of 311 cases, 1996-2005.
AB  - This study reviewed records of all electrical incidents involving work-related
      injury to employees Electricite de France (EDF) from 1996 through 2005 and
      analysed data for 311 incidents. The results are compared with 1231 electrical
      incidents that occurred during 1970-1979 and 996 incidents during 1980-1989. A
      total of 311 electrical incidents were observed. The medical consequences of
      electrical incident remain severe and particularly, the current fatality rate
      (3.2%) is similar to that recorded in the 1980s (2.7%) and 1970s (3.3%). Among
      individuals with non-fatal incidents, any change has occurred in the prevalence
      of permanent functional sequelae (23.6% in the 1970s vs. 27.6% in the 1980s and
      32.5% currently). An increase in the incidence of neuropsychiatric sequelae (5.4%
      in the 1980s vs. 13% currently) has been observed and they are now the second
      most common type of sequelae after those directly related to burns. Among the
      neurological sequelae, peripheral nervous system disorders are the most common,
      as observed in the 1980s. Since the definition of post-traumatic stress disorder
      (PTSD) has changed between the two periods, we can only report that the current
      prevalence of PTSD is 7.6%. This study emphasises the need for specific
      management of neurological and psychological impairments after electrical
      injuries, including especially early recognition and initiation of effective
      treatment. 

PMID- 24028743
TI  - Postmortem analysis of cardiovascular deaths in schizophrenia: a 10-year review.
AB  - Schizophrenia is a devastating mental disorder, associated with mortality rates
      up to three times higher than those in the general population. This post-mortem
      study sought to investigate the causes of death in a consecutive series of
      schizophrenia cases, with a specific focus on cardiovascular disease and sudden
      death. A 10-year review of autopsies in schizophrenia related-cases performed at
      the Department of Forensic Medicine in Sydney, Australia was undertaken.
      Premorbid clinical and demographic information was recorded, as well as the key
      pathological findings and final cause of death. From 2003 to 2012, there were
      19,478 postmortem examinations performed of which 683 (3.5%) were deaths in
      people with a history of schizophrenia. In these cases, the mean age at death was
      51years (range 18-93years), with 43% in the 41-60year age group. Males comprised
      67% of cases. Overall, 62% of cases had a BMI>=25kg/m(2), indicating overweight
      or obese individuals. The three primary causes of death were "cardiovascular"
      (23%), "suicide" (20%), and "drug toxicity" (17%). In 11% of cases (n=72), no
      definitive cause of death was found, the so-called "unexplained" cases. In
      conclusion, patients with schizophrenia have premature mortality. The major
      contributing factors include cardiovascular diseases, suicide and drug toxicity.
      The "unexplained" and frequently sudden deaths may suggest underlying cardiac
      arrhythmias as a cause of death in a subgroup of schizophrenia patients. 

PMID- 24028744
TI  - Issues and perspectives in designing clinical trials for negative symptoms in
      schizophrenia.
AB  - A number of pharmacological agents for treating negative symptoms in
      schizophrenia are currently in development. Unresolved questions regarding the
      design of clinical trials in this area were discussed at an international meeting
      in Florence, Italy in April 2012. Participants included representatives from
      academia, the pharmaceutical industry, and the European Medicines Agency (EMA).
      Prior to the meeting, participants submitted key questions for debate and
      discussion. Responses to the questions guided the discussion during the meeting.
      The group reached agreement on a number of issues: (1) study subjects should be
      under the age of 65; (2) subjects should be excluded for symptoms of depression
      that do not overlap with negative symptoms; (3) functional measures should not be
      required as a co-primary in negative symptom trials; (4) information from
      informants should be included for ratings when available; (5) Phase 2 negative
      symptom trials should be 12weeks and 26weeks is preferred for Phase 3 trials; (6)
      prior to entry into a negative symptom study, subjects should demonstrate
      clinical stability for a period of 4 to 6months by collection of retrospective
      information; and (7) prior to entry, the stability of negative and positive
      symptoms should be confirmed prospectively for four weeks or longer. The
      participants could not reach agreement on whether predominant or prominent
      negative symptoms should be required for study subjects. 

PMID- 24028745
TI  - Estimated dopamine D2 receptor occupancy from plasma concentrations of atypical
      antipsychotics and subjective experience/drug attitude in schizophrenia: an
      analysis of the CATIE data.
AB  - OBJECTIVE: The objective of this analysis was to evaluate both cross-sectional
      and longitudinal relationships between estimated dopamine D2 receptor occupancy
      from plasma concentrations of atypical antipsychotics and subjective
      experience/drug attitude in patients with schizophrenia. METHOD: The data from
      the Clinical Antipsychotic Trials in Intervention Effectiveness (CATIE) were used
      in this analysis. The cross-sectional data included 371 patients receiving
      risperidone, olanzapine, or ziprasidone, who had completed the Drug Attitude
      Inventory (DAI-10) at six months and provided plasma antipsychotic
      concentrations. Samples were analyzed to examine the relationship between DAI-10
      total scores and estimated D2 occupancy using Spearman's rank correlations,
      followed by multiple regression analysis. In addition, to elucidate the
      relationship between changes in DAI-10 scores and estimated D2 occupancy, the
      longitudinal data from 45 patients who experienced an increase in antipsychotic
      dosage between six and 12months were analyzed. Mean peak and trough D2 occupancy
      levels were estimated from plasma antipsychotic concentrations using a population
      pharmacokinetic approach. RESULTS: A positive association was found between
      estimated D2 occupancy and DAI-10 total scores in patients receiving ziprasidone
      in the cross-sectional dataset (rs=0.395, P=0.001). In contrast, a negative
      association was found in changes in estimated D2 occupancy and DAI-10 scores
      among patients receiving olanzapine in the longitudinal dataset (rs=-0.534,
      P=0.010). No significant associations were found in patients receiving
      risperidone, or in the whole sample regarding both cross-sectional and
      longitudinal datasets. CONCLUSION: Dopamine D2 receptor occupancy may mediate
      subjective experience/drug attitude in patients with schizophrenia. The
      directionality may however differ between antipsychotics, which warrants further
      investigation.

PMID- 24028746
TI  - Moral challenges with surgical treatment of type 2 diabetes.
AB  - AIM: To review the most important moral challenges following from the widespread
      use of bariatric surgery for type 2 diabetes for patients with BMI <35kg/m(2),
      although high quality evidence for its short and long term effectiveness and
      safety is limited. METHODS: Extensive literature search to identify and analyze
      morally relevant issues. A question based method in ethics was applied to
      facilitate assessment and decision making. RESULTS: Several important moral
      issues were identified: assessing and informing about safety, patient outcomes,
      and stakeholder interests; acquiring valid informed consent; defining and
      selecting outcome measures; stigmatization and discrimination of the patient
      group, as well as providing just distribution of health care. The main sources of
      these challenges are lack of high quality evidence, disagreement on clinical
      indications and endpoints, and the disciplining of human behavior by surgical
      interventions. CONCLUSION: A lack of high quality evidence on the effect of
      bariatric surgery for the treatment of T2DM in patients with BMI<35/kg/m(2) poses
      a wide variety of moral challenges, which are important for decisions on the
      individual patient level, on the management level, and on the health policy
      making level. Strong preferences among surgeons and patients may hamper high
      quality research.

PMID- 24028747
TI  - Anti-interleukin-6 receptor antibody prevents systemic bone mass loss via
      reducing the number of osteoclast precursors in bone marrow in a collagen-induced
      arthritis model.
AB  - Systemic bone loss is a hallmark of rheumatoid arthritis (RA). Inflammatory
      cytokines such as interleukin (IL)-6 promote bone resorption by osteoclasts.
      Sphingosine-1-phosphate (S1P) controls the migration of osteoclast precursor
      cells (OCPs) between the blood and bone marrow, in part via S1P receptors (S1PR1
      and S1PR2) expressed on the surface of OCPs. OCPs (CD11b(+) Gr-1(low+med) )
      isolated from bone marrow of DBA/1J mice were stimulated with IL-6. S1P-directed
      chemotaxis of OCPs was evaluated using a transwell plate. mRNA expression of
      S1PR1 and S1PR2 was measured. DBA/1J mice were immunized with bovine type II
      collagen (days 0 and 21) and anti-mouse IL-6 receptor antibody (MR16-1) was
      administered on days 0 and/or 21. Trabecular bone volume was analysed using micro
      computed tomography. The percentage of OCPs in tibial bone marrow and S1PR1 and
      S1PR2 mRNA expression in OCPs were measured. IL-6 stimulation significantly
      decreased S1P-directed chemotaxis of OCPs. IL-6 induced S1PR2 mRNA expression,
      but not S1PR1 mRNA expression, in OCPs. Bone volume was significantly lower in
      arthritic mice than in non-arthritic control mice on day 35. Treatment of
      immunized mice with MR16-1 significantly inhibited bone loss. In MR16-1-treated
      mice, the percentage of OCPs and expression of S1PR2 mRNA was each decreased
      compared with arthritic mice on day 14, but not on day 35. IL-6 increased the
      number of OCPs in tibial bone marrow via up-regulating S1PR2, thus playing a
      crucial role in systemic bone loss induced by inflammation. 

PMID- 24028748
TI  - Pediatric anaphylaxis management in the prehospital setting.
AB  - PURPOSE: Anaphylaxis is a life-threatening systemic allergic reaction that occurs
      after contact with an allergy-causing substance. Timely administration of
      intramuscular epinephrine is the treatment of choice for controlling symptoms and
      decreasing fatalities. Our purpose was to investigate the prehospital management
      of anaphylaxis among patients receiving care in an urban tertiary care pediatric
      emergency department (PED). METHODS: We performed a retrospective chart review
      from May 2008 to January 2010 of patients 18 years or younger who received care
      in the PED for anaphylaxis. Data were extracted by one investigator and included
      demographic information, patient symptoms, past medical history, medications
      administered (including route and provider), and final disposition. RESULTS: We
      reviewed 218 cases of anaphylaxis in 202 children. Mean age of patients was 7.4
      years; 56% of patients were male. A total of 214 (98%) manifested symptoms in the
      skin/mucosal system, 68% had respiratory symptoms, 44% had gastrointestinal
      symptoms, and 2% had hypotension. Sixty-seven percent had a previous history of
      allergic reaction and 38% had a history of asthma. Seventy-six percent of the
      patients presented with anaphylaxis to food products, 8% to medications, 1% to
      stings, and 16% to unknown allergens. Reactions occurred at home or with family
      members 87% of the time, and at school 12% of the time. Only 36% of the patients
      who met criteria for anaphylaxis had epinephrine administered by emergency
      medical services (EMS). Among 26 patients with anaphylactic reactions at school,
      69% received epinephrine by the school nurse. Of the 117 patients with known
      allergies who were with their parents at the time of anaphylactic reaction, 41%
      received epinephrine. Thirteen patients were seen by a physician prior to coming
      to the PED; all received epinephrine at the physician's office. In total,
      epinephrine was given to 41% (89) of the 218 cases prior to coming to the PED.
      CONCLUSIONS: Our evaluation revealed low rates of epinephrine administration by
      EMS providers and parents/patients. Education about anaphylaxis is imperative to
      encourage earlier administration of epinephrine.

PMID- 24028749
TI  - Administration of the etonogestrel contraceptive implant on the day of
      mifepristone for medical abortion: a pilot study.
AB  - OBJECTIVE: We sought to determine satisfaction and continuation rates of the
      contraceptive implant when placed on the initial visit for first-trimester
      medical abortion. STUDY DESIGN: In this pilot study, we placed the implant within
      15 min of mifepristone administration. We assessed satisfaction with implant
      placement timing, 1-year implant continuation and abortion completion. RESULTS:
      We enrolled 20 participants. Sixteen (80%) returned for follow-up, and all had
      complete abortion. At 1 year, of 16 participants contacted, 14 (87.5%) were
      satisfied with implant insertion timing, and 14 (87.5%) continued the implant.
      CONCLUSIONS: Initiation of the contraceptive implant on the initial visit for
      medical abortion resulted in high satisfaction and continuation rates.
      IMPLICATIONS: This pilot study provides important groundwork for future larger
      studies to assess initiation of the contraceptive implant on the day of
      mifepristone for medical abortion.

PMID- 24028750
TI  - Patient viewing of the ultrasound image prior to abortion.
AB  - BACKGROUND: Little research has investigated women's interest in and factors
      associated with viewing their ultrasound image in abortion care. STUDY DESIGN:
      Using medical records for all abortion care visits in 2011 (n = 15,575) at an
      urban abortion provider, we determined the proportion of women who chose to view
      by sociodemographic and pregnancy-related characteristics. We used bivariate and
      multivariable mixed-effects logistic regression models to examine associations
      between individual-level factors and the decision to view. RESULTS: A total of
      42.6% of women chose to view. Identifying as nonwhite, being under age 25, being
      at or below the federal poverty level, and having medium or low decision
      certainty about the abortion were associated with increased odds of viewing.
      Being age 30 and over, having previously been pregnant and being more than 9
      weeks gestation were associated with decreased odds of viewing. CONCLUSIONS: Many
      women seeking abortion care want to view their ultrasound image when offered the
      opportunity.

PMID- 24028751
TI  - Potential unintended pregnancies averted and cost savings associated with a
      revised Medicaid sterilization policy.
AB  - OBJECTIVE: Medicaid sterilization policy, which includes a mandatory 30-day
      waiting period between consent and the sterilization procedure, poses significant
      logistical barriers for many women who desire publicly funded sterilization. Our
      goal was to estimate the number of unintended pregnancies and the associated
      costs resulting from unfulfilled sterilization requests due to Medicaid policy
      barriers. STUDY DESIGN: We constructed a cost-effectiveness model from the health
      care payer perspective to determine the incremental cost over a 1-year time
      horizon of the current Medicaid sterilization policy compared to a hypothetical,
      revised policy in which women who desire a postpartum sterilization would face
      significantly reduced barriers. Probability estimates for potential outcomes in
      the model were based on published sources; costs of Medicaid-funded
      sterilizations and Medicaid-covered births were based on data from the Medicaid
      Statistical Information System and The Guttmacher Institute, respectively.
      RESULTS: With the implementation of a revised Medicaid sterilization policy, we
      estimated that the number of fulfilled sterilization requests would increase by
      45%, from 53.3% of all women having their sterilization requests fulfilled to
      77.5%. Annually, this increase could potentially lead to over 29,000 unintended
      pregnancies averted and $215 million saved. CONCLUSION: A revised Medicaid
      sterilization policy could potentially honor women's reproductive decisions,
      reduce the number of unintended pregnancies and save a significant amount of
      public funds. IMPLICATION: Compared to the current federal Medicaid sterilization
      policy, a hypothetical, revised policy that reduces logistical barriers for women
      who desire publicly funded, postpartum sterilization could potentially avert over
      29,000 unintended pregnancies annually and therefore lead to cost savings of $215
      million each year.

PMID- 24028752
TI  - Detection of two biological markers of intercourse: prostate-specific antigen and
      Y-chromosomal DNA.
AB  - BACKGROUND: Although biological markers of women's exposure to semen from vaginal
      intercourse have been developed as surrogates for risk of infection or
      probability of pregnancy, data on their persistence time and clearance are
      limited. STUDY DESIGN: During 2006-2008, 52 couples were enrolled for three 14
      day cycles of abstinence from vaginal sex during which women were exposed in the
      clinic to a specific quantity (10, 100 or 1000 MUL) of their partner's semen.
      Vaginal swabs were collected before and at 1, 6, 12, 24, 48, 72 and 144 h after
      exposure for testing for prostate-specific antigen (PSA) and Y-chromosome DNA (Yc
      DNA). RESULTS: Immediately after exposure to 1000 MUL of semen, the predicted
      sensitivity of being PSA positive was 0.96; this decreased to 0.65, 0.44, 0.21
      and 0.07 at 6, 12, 24 and 48 h, respectively. Corresponding predicted sensitivity
      of being Yc DNA positive was 0.72 immediately postexposure; this increased to
      0.76 at 1 h postexposure and then decreased to 0.60 (at 6 h), 0.63 (at 12 h),
      0.49 (at 24 h), 0.21 (at 48 h), 0.17 (at 72 h) and 0.12 (at 144 h). CONCLUSIONS:
      Overall findings suggest that PSA may be more consistent as a marker of very
      recent exposure and that Yc DNA is more likely to be detected in the vagina after
      12 h postexposure compared to PSA.

PMID- 24028753
TI  - Controversies in family planning: how to manage a fractured IUD.

PMID- 24028754
TI  - Evaluation of the immune factors in the tumor environment before and after the
      treatment of cetuximab combined with chemotherapy.
AB  - BACKGROUND: The effect of chemotherapy combined with monoclonal antibodies (mAbs)
      on the immune state of the tumor environment remains unclear and controversial.
      The aim of this study is to examine the effect of chemotherapy combined with
      cetuximab (C225, an anti-EGFR mAb) on the immune state of tumor environment, and
      the correlation of that effect and the clinical efficacy. METHODS: Twelve
      patients with colorectal cancer, who received the treatment of chemotherapy
      combined with C225, were enrolled in this study. The tumor specimen of the
      primary colorectal cancer before and after treatment was obtained. The expression
      of a series of immune factors (TGF-beta1, CD8, IL-2, TNF-alpha, and VEGF) was
      measured by immunochemistry. The expression of these immune factors before and
      after treatment was compared by the Wilcoxon signed-rank test. The correlation of
      the change of immune parameter expression after treatment and clinical efficacy
      was examined by chi-square tests. The correlation of the expression of immune
      factors, clinical efficacy, and treatment number was examined by the Spearman's
      correlation analysis. RESULTS: There was no significant difference between the
      expression of TGF-beta1 before and after the treatment (P >0.05). The change of
      TGF-beta1 expression after treatment significantly correlated negatively with
      clinical efficacy (P = 0.05). As for CD8, IL-2, VEGF, and TNF-alpha, there were
      no significant differences between the expression before and after the treatment
      (P >0.05), and the change of expression after treatment also did not correlate
      significantly with clinical efficacy (P >0.05). The change of IL-2 expression
      after treatment significantly correlated negatively with treatment number
      (correlation coefficient = -0.585, P = 0.046). The change of TGF-beta1 expression
      after treatment significantly correlated negatively with clinical efficacy
      (correlation coefficient = -0.684, P = 0.014). Before treatment, the expression
      of TNF-alpha significantly correlated positively with the expression of IL-2
      (correlation coefficient = 0.629, P = 0.028). After treatment, the expression of
      TGF-beta1 significantly correlated negatively with the expression of CD8
      (correlation coefficient = -0.664, P = 0.019). CONCLUSIONS: These results
      suggested that, in the tumor environment, the change of immune factors after
      treatment of cetuximab combined with chemotherapy may be associated with clinical
      efficacy.

PMID- 24028756
TI  - Thrombin activatable fibrinolysis inhibitor in cancer patients with and without
      venous thromboembolism.

PMID- 24028755
TI  - Beta-Agonist Lung injury TrIal-2 (BALTI-2): a multicentre, randomised, double
      blind, placebo-controlled trial and economic evaluation of intravenous infusion
      of salbutamol versus placebo in patients with acute respiratory distress
      syndrome.
AB  - BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major cause of
      mortality in intensive care patients and lacks effective treatments. A previous
      randomised controlled Phase II trial suggested that an intravenous (i.v.)
      infusion of salbutamol may be beneficial, as it reduced extravascular lung water
      and plateau airway pressure. The Beta-Agonist Lung injury TrIal-2 (BALTI-2) was
      initiated to evaluate the effects of this intervention on mortality in patients
      with ARDS. OBJECTIVES: To evaluate whether or not, in patients with ARDS, an i.v.
      infusion of salbutamol given at 15 MUg/kg ideal body weight (IBW)/hour for up to
      7 days, compared with a placebo (0.9% sodium chloride) infusion, reduces 28-day
      all-cause mortality and other clinical outcomes. To evaluate salbutamol's
      clinical effectiveness and its cost-effectiveness in subgroups of patients.
      DESIGN: A multicentre, randomised, placebo-controlled trial. SETTING: Forty-six
      intensive care units (ICUs) in the UK. PARTICIPANTS: Patients were eligible if
      they (1) were intubated and mechanically ventilated patients in participating
      ICUs; (2) were within 72 hours of onset of ARDS; (3) fulfilled American-European
      Consensus Conference definition for ARDS {acute-onset, severe hypoxaemic
      respiratory failure [partial pressure of oxygen in arterial blood/fraction of
      inspired oxygen <= 26.7 kPa (200 mmHg)] and bilateral infiltrates on the chest
      radiograph in the absence of clinical evidence of left atrial hypertension}; and
      (4) were aged >= 16 years. INTERVENTIONS: Intravenous infusion of salbutamol (15
      MUg/kg IBW/hour) or placebo (0.9% saline) for up to 7 days. MAIN OUTCOME
      MEASURES: All-cause mortality 28 days after randomisation, mortality at (first)
      discharge from ICU, mortality at (first) discharge from hospital, number of
      ventilator-free days, number of organ failure-free days, mortality at 12 months
      post randomisation, side effects (tachycardia/new arrhythmia/lactic acidosis)
      sufficient to stop treatment with trial drug, health-related quality of life
      (European Quality of Life-5 Dimensions and Short Form questionnaire-12 items at 6
      and 12 months after randomisation), length of stay in critical care unit and
      length of stay in hospital. RESULTS: Forty-six ICUs recruited patients to the
      trial. A total of 326 patients were randomised; 162 were allocated to salbutamol
      and 164 to placebo. One patient in each group withdrew consent. Recruitment was
      stopped after the second interim analysis because of safety concerns. Salbutamol
      increased 28-day mortality: 55 (34%) of 161 patients died in the salbutamol group
      compared with 38 (23%) of 163 in the placebo group (risk ratio 1.47, 95%
      confidence interval 1.03 to 2.08). CONCLUSIONS: Treatment with i.v. salbutamol
      early in the course of ARDS was poorly tolerated, is unlikely to be beneficial
      and could worsen outcomes. Further trials of beta-agonists in patients with ARDS
      are unlikely to be conducted. Some questions remain, such as whether or not there
      may be benefit at a different dose or in specific populations, but any studies
      investigating these would require a very strong rationale. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN38366450. FUNDING: The National Institute for
      Health Research Health Technology Assessment programme.

PMID- 24028757
TI  - Technological innovation in the BJUI.

PMID- 24028758
TI  - Reach for the sky - tissue engineering in urology.

PMID- 24028759
TI  - Fluorodeoxyglucose positron-emission tomography (FDG PET)/computed tomography
      (CT) in bladder cancer.

PMID- 24028760
TI  - Does inflammation reduce the risk of prostate cancer?

PMID- 24028761
TI  - Minimally invasive vs open radical prostatectomy in high-risk prostate cancer:
      comparing apples and pears?

PMID- 24028762
TI  - If it's not broken - fix it.

PMID- 24028763
TI  - Comparative assessment of three standardized robotic surgery training methods.

PMID- 24028764
TI  - TOOKAD((r)) Soluble vascular-targeted photodynamic (VTP) therapy: determination
      of optimal treatment conditions and assessment of effects in patients with
      localised prostate cancer.
AB  - OBJECTIVES: To evaluate the optimal treatment conditions and effects of
      TOOKAD((r)) Soluble vascular-targeted photodynamic (VTP) therapy in patients with
      localised prostate cancer. To evaluate the safety and quality of life after
      TOOKAD((r)) Soluble VTP treatment in patients with localised prostate cancer.
      PATIENTS AND METHODS: Men (aged >18 years) diagnosed with localised prostate
      cancer, who were suitable for active surveillance, were invited to take part in
      the study. Patients who had received prior or current treatment for their cancer
      were excluded. There were two parts to the study: in part one, patients were
      assigned to one of two treatment groups based on the size of their prostates
      (patients with prostate size <60 mL would receive 4 mg/kg TOOKAD((r)) Soluble and
      patients with prostate size >=60 mL would receive 6 mg/kg TOOKAD((r)) Soluble
      both activated with 200 J/cm light). In part two, patients were assigned to one
      of two treatment groups based on predefined criteria and received either 4 or 6
      mg/kg TOOKAD((r)) Soluble and 200 or 300 J/cm light. VTP was conducted under
      general anaesthesia using TOOKAD((r)) Soluble administered intravenously and
      activated by light-diffusing fibres within the prostate via the perineum. Follow
      up was conducted for 6 months. Magnetic resonance imaging (MRI) carried out at 1
      week after VTP and transrectal prostate biopsy at 6 months were the key
      endpoints. Adverse event (AE) recording and patient-reported outcome measures
      were collected. RESULTS: In all, 86 patients were enrolled in the study and 85
      patients received treatment. Of the 85 treated patients, one patient discontinued
      (due to withdrawal of consent). At 6 months, 61/83 (74%) patients who underwent
      prostate biopsy had histopathology that was negative for prostate cancer (95%
      confidence interval (CI) 62.7-82.6%). Considering patients who received 4 mg/kg
      TOOKAD((r)) Soluble and 200 J/cm light (unilateral), which are considered optimal
      treatment parameters, 38/46 (83%) patients had histopathology from the biopsies
      that was negative for prostate cancer at 6 months (95% CI 68.6-92.2%; P < 0.001).
      The mean percentage of necrosis of the targeted prostate tissue at 7 days after
      VTP was 78% overall (83 patients) with extraprostatic necrosis reported in 76%
      (63/83) of patients. Considering patients who received 4 mg/kg TOOKAD((r))
      Soluble and 200 J/cm light (unilateral), the mean 7-day necrosis percentage was
      88% (46 patients) with extraprostatic necrosis reported in 72% (33/46) of
      patients. All occurrences of extraprostatic necrosis were considered clinically
      acceptable and none were associated with any clinical sequelae. The mean
      percentage prostate necrosis at 7 days was statistically significantly higher (P
      < 0.001) in patients treated with a therapeutic light density index (LDI) of >=1
      than those treated with a LDI of <1. The percentage of patients with negative
      biopsies at 6 months was also higher in patients treated with a therapeutic LDI
      of >=1 than those treated with a LDI of <1 (78.6% and 63.0%, respectively). In
      all, 87% (75/86) of patients reported at least one treatment-emergent AE during
      the study. Most AEs were mild or moderate in intensity and considered related to
      the technical procedures of the study. No treated patients had hypotension or
      discontinued due to AEs. Eight patients (9.3%) had serious AEs; none resulted in
      discontinuation from the study. CONCLUSIONS: Biopsy data, post-treatment dynamic
      contrast-enhancement MRI at 1 week after VTP and analysis of the safety data have
      shown that 4 mg/kg TOOKAD((r)) Soluble and 200 J/cm light are the optimal
      treatment conditions for the VTP procedure resulting in >80% of patients treated
      with this regimen having a negative biopsy at 6 months. Overall, the treatment
      was well tolerated and exhibited early signs of efficacy for minimally invasive
      focal treatment of localised prostate cancer.

PMID- 24028765
TI  - Influence of nutritional deficiency on prognosis of renal cell carcinoma (RCC).
AB  - OBJECTIVE: To evaluate the prognosis of patients with renal cell carcinoma (RCC)
      by nutritional status defined by body mass index (BMI), serum albumin and
      cholesterol. PATIENTS AND METHODS: This study retrospectively enrolled 1437
      patients who underwent radical nephrectomy (932) or partial nephrectomy (505) for
      RCC. We assigned nutritional status according to the presence of none or one
      nutritional risk factor (control group) and two or all three of the following
      nutritional risk factors (nutritional deficiency group). The nutritional factors
      and thresholds were preoperative albumin level (<3.5 g/dL), preoperative
      cholesterol level (<220 mg/dL), and preoperative BMI (<23 kg/m(2) ) RESULTS: The
      patients' mean (sd) age was 55.23 (12.41) years and BMI was 24.36 (3.17) kg/m(2)
      . The mean (sd) serum cholesterol level was 180.07 (38.24) mg/dL, and the albumin
      level was 4.2 (0.45) g/dL. In all, 141 (9.8%) patients had none of the
      nutritional deficiency criteria, 802 (55.8%) had one, 429 (29.9%) had two, and 65
      (4.5%) had all three. Clinicopathological variables, i.e. female gender, high
      tumour stage, positive lymph node metastasis, positive distant metastasis, high
      nuclear grade and non-clear cell type histopathology were associated with the
      nutritional deficiency group. In multivariate Cox analysis, nutritional
      deficiency was an independent predictor for RCC recurrence (hazard ratio [HR]
      1.39, 95% confidence interval [CI] 1.05-1.83, P = 0.020) and RCC-related
      mortality (HR 2.06, 95% CI 1.39-3.03, P < 0.001). CONCLUSION: Nutritional
      deficiency defined by BMI, serum albumin and cholesterol is an important factor
      that predicts postoperative prognosis of patients with RCC who have undergone
      radical or partial nephrectomy.

PMID- 24028766
TI  - Modulating the immune response to Bacillus Calmette-Guerin (BCG): a novel way to
      increase the immunotherapeutic effect of BCG for treatment of bladder cancer?

PMID- 24028767
TI  - Endometrial stem cell differentiation into smooth muscle cell: a novel approach
      for bladder tissue engineering in women.
AB  - OBJECTIVE: To investigate manufacturing smooth muscle cells (SMCs) for
      regenerative bladder reconstruction from differentiation of endometrial stem
      cells (EnSCs), as the recent discovery of EnSCs from the lining of women's uteri,
      opens up the possibility of using these cells for tissue engineering
      applications, such as building up natural tissue to repair prolapsed pelvic
      floors as well as building urinary bladder wall. MATERIALS AND METHODS: Human
      EnSCs that were positive for cluster of differentiation 146 (CD146), CD105 and
      CD90 were isolated and cultured in Dulbecco's modified Eagle/F12 medium
      supplemented with myogenic growth factors. The myogenic factors included:
      transforming growth factor beta, platelet-derived growth factor, hepatocyte
      growth factor and vascular endothelial growth factor. Differentiated SMCs on
      bioabsorbable polyethylene-glycol and collagen hydrogels were checked for SMC
      markers by real-time reverse-transcriptase polymerase chain reaction (RT-PCR),
      western blot (WB) and immunocytochemistry (ICC) analyses. RESULTS: Histology
      confirmed the growth of SMCs in the hydrogel matrices. The myogenic growth
      factors decreased the proliferation rate of EnSCs, but they differentiated the
      human EnSCs into SMCs more efficiently on hydrogel matrices and expressed
      specific SMC markers including alpha-smooth muscle actin, desmin, vinculin and
      calponin in RT-PCR, WB and ICC experiments. The survival rate of cultures on the
      hydrogel-coated matrices was significantly higher than uncoated cultures.
      CONCLUSIONS: Human EnSCs were successfully differentiated into SMCs, using
      hydrogels as scaffold. EnSCs may be used for autologous bladder wall regeneration
      without any immunological complications in women. Currently work is in progress
      using bioabsorbable nanocomposite materials as EnSC scaffolds for developing
      urinary bladder wall tissue.

PMID- 24028768
TI  - Detecting minimal residual disease in patients with chronic lymphocytic leukemia
      using 8-color flow cytometry protocol in routine hematological practice.
AB  - INTRODUCTION: Minimal residual disease (MRD) detection has become increasingly
      important for the assessment of therapy response in chronic lymphocytic leukemia
      (CLL). However, current MRD analysis methods, both molecular genetic and flow
      cytometric, are time-consuming and require experienced laboratory staff. METHODS:
      To reduce the demands of flow cytometric MRD detection in CLL, we have introduced
      a novel flow cytometric 8-color protocol. The MRD analysis results using this
      protocol were then compared with the commonly employed 4-color protocol and the
      molecular genetic (real-time quantitative allele-specific oligonucleotide IGH
      polymerase chain reaction; RQ-ASO IGH PCR) approach. RESULTS: Forty-two CLL
      patient samples were repeatedly analyzed after allogeneic stem cell
      transplantation (n = 20) or after fludarabine-based therapy (n = 22), and 100%
      concordance was found using both flow cytometric protocols. Furthermore, there
      was a strong correlation (r = 0.94) between flow cytometric and RQ-ASO IGH PCR
      results in MRD detection. CONCLUSION: Flow cytometry is less time-consuming, less
      financially demanding, and moreover, MRD assessment using our novel 8-color
      protocol is less complicated than the 4-color approach and molecular methods.

PMID- 24028769
TI  - Turn-on fluorescent InP nanoprobe for detection of cadmium ions with high
      selectivity and sensitivity.
AB  - We reported a "turn-on" fluorescent InP nanoprobe for detection of cadmium ions
      in hydrophobic and hydrophilic media. The method based on the turn-on
      fluorescence detection of cadmium ions has shown its high selectivity and
      sensitivity, which are independent of the pH of the tested samples. Also, this
      approach exhibits an immediate response to cadmium ions, and visualized detection
      of cadmium ions has further been demonstrated under a UV lamp. 

PMID- 24028770
TI  - PU.1 target genes undergo Tet2-coupled  demethylation and DNMT3b-mediated 
      methylation in monocyte-to-osteoclast  differentiation.
AB  - BACKGROUND: DNA methylation is a key epigenetic mechanism for driving and
      stabilizing cell-fate decisions. Local deposition and removal of DNA methylation
      are tightly coupled with transcription factor binding, although the relationship
      varies with the specific differentiation process. Conversion of monocytes to
      osteoclasts is a unique terminal differentiation process within the hematopoietic
      system. This differentiation model is relevant to autoimmune disease and cancer,
      and there is abundant knowledge on the sets of transcription factors involved.
      RESULTS: Here we focused on DNA methylation changes during osteoclastogenesis.
      Hypermethylation and hypomethylation changes took place in several thousand
      genes, including all relevant osteoclast differentiation and function categories.
      Hypomethylation occurred in association with changes in 5-hydroxymethylcytosine,
      a proposed intermediate toward demethylation. Transcription factor binding motif
      analysis revealed an over-representation of PU.1, NF-kappaB, and AP-1 (Jun/Fos)
      binding motifs in genes undergoing DNA methylation changes. Among these, only
      PU.1 motifs were significantly enriched in both hypermethylated and
      hypomethylated genes; ChIP-seq data analysis confirmed its association to both
      gene sets. Moreover, PU.1 interacts with both DNMT3b and TET2, suggesting its
      participation in driving hypermethylation and hydroxymethylation-mediated
      hypomethylation. Consistent with this, siRNA-mediated PU.1 knockdown in primary
      monocytes impaired the acquisition of DNA methylation and expression changes, and
      reduced the association of TET2 and DNMT3b at PU.1 targets during osteoclast
      differentiation. CONCLUSIONS: The work described here identifies key changes in
      DNA methylation during monocyte-to-osteoclast differentiation and reveals novel
      roles for PU.1 in this process.

PMID- 24028771
TI  - Characteristics and outcomes of culture-negative versus culture-positive severe
      sepsis.
AB  - INTRODUCTION: Culture-negative sepsis is a common but relatively understudied
      condition. The aim of this study was to compare the characteristics and outcomes
      of culture-negative versus culture-positive severe sepsis. METHODS: This was a
      prospective observational cohort study of 1001 patients who were admitted to the
      medical intensive care unit (ICU) of a university hospital from 2004 to 2009 with
      severe sepsis. Patients with documented fungal, viral, and parasitic infections
      were excluded. RESULTS: There were 415 culture-negative patients (41.5%) and 586
      culture-positive patients (58.5%). Gram-positive bacteria were isolated in 257
      patients, and gram-negative bacteria in 390 patients. Culture-negative patients
      were more often women and had fewer comorbidities, less tachycardia, higher blood
      pressure, lower procalcitonin levels, lower Acute Physiology and Chronic Health
      Evaluation II (median 25.0 (interquartile range 19.0 to 32.0) versus 27.0 (21.0
      to 33.0), P = 0.001) and Sequential Organ Failure Assessment scores, less
      cardiovascular, central nervous system, and coagulation failures, and less need
      for vasoactive agents than culture-positive patients. The lungs were a more
      common site of infection, while urinary tract, soft tissue and skin infections,
      infective endocarditis and primary bacteremia were less common in culture
      negative than in culture-positive patients. Culture-negative patients had a
      shorter duration of hospital stay (12 days (7.0 to 21.0) versus 15.0 (7.0
      to27.0), P = 0.02) and lower ICU mortality than culture-positive patients.
      Hospital mortality was lower in the culture-negative group (35.9%) than in the
      culture-positive group (44.0%, P = 0.01), the culture-positive subgroup, which
      received early appropriate antibiotics (41.9%, P = 0.11), and the culture
      positive subgroup, which did not (55.5%, P < 0.001). After adjusting for
      covariates, culture positivity was not independently associated with mortality on
      multivariable analysis. CONCLUSIONS: Significant differences between culture
      negative and culture-positive sepsis are identified, with the former group having
      fewer comorbidities, milder severity of illness, shorter hospitalizations, and
      lower mortality.

PMID- 24028772
TI  - Factor VIII concentrate infusion in patients with haemophilia results in
      decreased von Willebrand factor and ADAMTS-13 activity.
AB  - The effects of coagulation factor concentrate infusion on restoring secondary
      haemostasis in patients with haemophilia are obvious. It is not known whether
      coagulation factor concentrate infusion affects primary haemostasis or induces an
      acute inflammatory response. In this study, the influence of a factor VIII
      (FVIII) concentrate bolus infusion on platelet activation and responsiveness,
      endothelial activation, and inflammation in adult patients with severe
      haemophilia A was assessed. VWF showed a mild, but significant decrease 15 min
      after FVIII infusion (85.02 IU dL(-1)) vs. before infusion (92.04 IU dL(-1) ; P =
      0.017), while ADAMTS-13 levels also show a mild but significant decrease from
      66.1 ng mL(-1) before infusion, to 53.9 ng mL(-1) (P = 0.012) 15 min after and
      50.8 ng mL(-1) (P = 0.050) 60 min after infusion. Platelet P-selectin expression
      decreased 15 min (33.3 AU) and 60 min (38.7 AU) after infusion compared to before
      infusion (41.3 AU; P = 0.018 and 0.036). In conclusion, a single infusion of a
      high dose FVIII concentrate in haemophilia A patients may influence primary
      haemostasis by decreasing VWF, ADAMTS-13 and the number of circulating activated
      platelets. These effects possibly occur as a consequence of binding of the
      infused FVIII to VWF, influencing its processing. When treating severe
      haemophilia A patients with coagulation concentrate infusion, one should realize
      this does not merely correct FVIII levels but also may influence primary
      haemostasis.

PMID- 24028773
TI  - Death receptor 6 is epigenetically silenced by histone deacetylation in
      endometriosis and promotes the pathogenesis of endometriosis.
AB  - PROBLEM: The purpose of this study is to evaluate the involvement of death
      receptor (DR) 6 in the pathogenesis of endometriosis. METHODS OF STUDY:
      Endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells
      (NESCs) were isolated from ovarian endometriotic tissues and the eutopic
      endometrial tissues, respectively. The effect of valproic acid (VPA) on the DR6
      expression in ECSCs was examined. The roles of DR6 in NESC proliferation and
      apoptosis were investigated with DR6 siRNA transfection. The distribution of DR6
      protein in ovarian endometriotic tissues and normal proliferative-phase
      endometrium was examined by immunohistochemistry. The expression of DR6 mRNA and
      protein in ECSCs and NESCs was also examined. RESULTS: Death receptor 6
      expression was attenuated in ECSCs and in endometriotic tissues, and its
      expression was upregulated by VPA stimulation. VPA treatment resulted in an
      accumulation of acetylated histone H4 in the promoter region of the DR6 gene. DR6
      knockdown directed the stimulation of cell proliferation and the resistance to
      apoptosis in NESCs. CONCLUSION: The present findings suggested that DR6 is
      involved in the pathogenesis of endometriosis by creating the proliferative and
      anti-apoptotic characteristics of endometriosis. The results also suggest that
      histone deacetylase inhibitors are promising agents for the treatment of
      endometriosis.

PMID- 24028774
TI  - Dynamic compression plate (DCP) fixation of propagating medial condylar fractures
      of the third metacarpal/metatarsal bone in 30 racehorses: retrospective analysis
      (1990-2005).
AB  - REASONS FOR PERFORMING STUDY: An in-depth review of dynamic compression plate
      (DCP) fixation of propagating medial condyle fractures of the third metacarpus or
      metatarsus has not been previously reported. OBJECTIVES: To describe the
      technique, evaluate short-term outcome and long-term race performance of
      racehorses that underwent DCP fixation for repair of propagating or spiralling
      medial condylar fractures of the third metacarpal (McIII) or metatarsal (MtIII)
      bone. STUDY DESIGN: Retrospective case series. METHODS: The surgical case records
      of 30 horses with propagating fractures of the medial condyle of McIII or MtIII
      were reviewed. Medical information included: age, breed, sex, presentation, how
      injury occurred (racing or training), surgical treatment and post operative
      complications. Racing information included: starts, top 3 placing and career
      earnings. RESULTS: Long propagating fractures of the medial condyle of Mc/tIII
      were identified in 23 Thoroughbred (TB) and 7 Standardbred (STB) racehorses. The
      fracture spiralled proximally in 22 of 30 cases (73%). Standardbreds had a higher
      propensity for hindlimb involvement (71%), whereas TBs tended to have more front
      limb involvement (61%). Twelve of 30 (40%) horses raced post surgery. Career
      earnings were significantly lower for TB horses with medial condylar fractures;
      $34,916 when compared with the national average of $60,841 (P<=0.03). Overall,
      horses having DCP fixation for medial condylar fractures had less starts post
      surgery (3.1 TBs and 5.8 STBs) compared with the national average (7 TBs and 17.3
      STBs) and decreased lifetime starts 13.4 (TBs) compared with 17.3 nationally.
      CONCLUSIONS: Propagating medial condyle fractures can be repaired with plate
      fixation to potentially lessen the risk of catastrophic fracture destabilisation
      and return to racing can be expected in 40% of horses. Further prospective
      studies are warranted comparing lag screw fixation with DCP fixation for repair
      of severe medial condylar fractures of the metacarpus/metatarsus.

PMID- 24028775
TI  - Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma".
AB  - This first German evidence-based guideline for cutaneous melanoma was developed
      under the auspices of the German Dermatological Society (DDG) and the
      Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German
      Guideline Program in Oncology. The recommendations are based on a systematic
      literature search, and on the consensus of 32 medical societies, working groups
      and patient representatives. This guideline contains recommendations concerning
      diagnosis, therapy and follow-up of melanoma. The diagnosis of primary melanoma
      based on clinical features and dermoscopic criteria. It is confirmed by
      histopathologic examination after complete excision with a small margin. For the
      staging of melanoma, the AJCC classification of 2009 is used. The definitive
      excision margins are 0.5 cm for in situ melanomas, 1 cm for melanomas with up to
      2 mm tumor thickness and 2 cm for thicker melanomas, they are reached in a
      secondary excision. From 1 mm tumor thickness, sentinel lymph node biopsy is
      recommended. For stages II and III, adjuvant therapy with interferon-alpha should
      be considered after careful analysis of the benefits and possible risks. In the
      stage of locoregional metastasis surgical treatment with complete lymphadenectomy
      is the treatment of choice. In the presence of distant metastasis mutational
      screening should be performed for BRAF mutation, and eventually for CKIT and NRAS
      mutations. In the presence of mutations in case of inoperable metastases targeted
      therapies should be applied. Furthermore, in addition to standard chemotherapies,
      new immunotherapies such as the CTLA-4 antibody ipilimumab are available. Regular
      follow-up examinations are recommended for a period of 10 years, with an
      intensified schedule for the first three years.

PMID- 24028777
TI  - Reproducibility of lactate markers during 4 and 8 min stage incremental running:
      a pilot study.
AB  - OBJECTIVES: This study examined the reproducibility of speed corresponding to
      specific lactate markers during incremental treadmill running of normal and
      prolonged stage durations. DESIGN: Nineteen healthy participants (14 male, 5
      female) performed repeated, incremental treadmill running trials of 4 and 8 min
      stages on separate days to examine the test-retest reproducibility of speed at
      lactate markers. Two trials were completed for each duration in a randomised
      order. METHODS: Fingertip blood samples drawn upon stage completion were analysed
      for plasma lactate, then used to determine running speed at: 2.0, 3.5, and 4.0
      mmol l(-1) fixed blood lactate accumulations (FBLA), a 1 mmol l(-1) rise from
      baseline, and the markers: the deviation maximum (Dmax), the Dmax of the second
      curve derivative (D2L(max)), the lactate threshold (LT) and log-log LT. RESULTS:
      The 2.0 mmol l(-1) FBLA reported the lowest mean bias between 4 min trials (-0.06
      km h(-1)), with the narrowest limits of agreement (LoA) (-1.78 to 1.66 km h(-1)).
      The Dmax had the second lowest bias (0.14 km h(-1)), D2L(max) the second
      narrowest LoA (-1.93 to 2.90 km h(-1)). For 8 min stages, the 1 mmol l(-1) rise
      demonstrated, low mean bias (-0.13 km h(-1)) and narrowest LoA (-1.22 to 0.97 km
      h(-1)) between trials. CONCLUSIONS: This preliminary report suggests the
      reproducibility of running speed at lactate summary markers is influenced by
      stage duration for incremental treadmill running. Varied marker reproducibility
      between 4 and 8 min stages indicates different blood lactate response, and
      therefore workload calculation, according to stage length. Consideration of
      marker construct is recommended.

PMID- 24028778
TI  - Contraception knowledge and attitudes: truths and myths among African Australian
      teenage mothers in Greater Melbourne, Australia.
AB  - AIMS AND OBJECTIVES: To discuss the contraception knowledge, attitudes and
      beliefs of African Australian teenagers and women with a refugee background in
      Melbourne. BACKGROUND: The numbers of African Australian persons continue to
      increase, with a significant proportion being refugee women and children.
      Attitudes and behaviours towards contraception in this group continue to be
      influenced by culture, family and beliefs. DESIGN: This study is based on
      qualitative research that was underpinned by intersectionality theory, cultural
      competency and phenomenology. PARTICIPANTS: Sixteen teenagers and women who had
      experienced teenage pregnancy in Greater Melbourne, Australia, were interviewed.
      METHODS: In-depth interviews were conducted with the sixteen African Australian
      teenagers and women. Following data collection, data were transcribed verbatim,
      and coded, and key themes identified and analysed using thematic analysis.
      RESULTS: Knowledge of contraception among this group of migrants was low and
      filled with myths. Attitudes towards contraception use were insufficient and
      influenced by beliefs and external factors such as partner, family and community
      attitudes towards contraception. Migration status and other instabilities in the
      lives of these participants all intersected to shape their health beliefs and
      contraception decision-making. CONCLUSIONS: Refugee teenage mothers' knowledge of
      contraception was low and their attitude towards contraceptive use was poor.
      Myths and external factors continued to influence teenagers' and women's
      attitudes towards contraceptives. The events and life experiences of African
      Australian teenagers/women, culture, and family and community influences should
      be taken into consideration when providing healthcare services and sexual health
      education to this migrant group. RELEVANCE TO CLINICAL PRACTICE: Service
      providers should consider the multiple intersections in the lives of these women
      when delivering healthcare services and information to them.

PMID- 24028779
TI  - [Hemostatic absorbable gel matrix for severe post-traumatic epistaxis].
AB  - INTRODUCTION: The management of traumatic epistaxis is an important issue for
      maxillofacial trauma patients, because of their frequency and severity. We
      assessed a single use sterile hemostatic gel matrix (surgiflo(c) [SF], Floseal
      (c) [FS]) available for this indication. MATERIALS AND METHODS: Ten patients were
      managed between 2008 and 2012 by the same surgeon. The following data was
      documented for each patient: gender, age, mechanism of trauma or type of surgery,
      characteristics of epistaxis, the various hemostatic techniques used before using
      SF, and its effectiveness. The primary endpoint was SF effectiveness compared
      with usual techniques. The secondary endpoint was the evaluation of patient
      comfort compared to other hemostatic methods, using a visual analogue scale
      (VAS). RESULTS: In nine out of ten cases, epistaxis was controlled after
      endonasal instillation of SF after failure of wicking, or double balloon catheter
      in first line treatment, or use of SF directly as first line treatment. The mean
      post procedure VAS was: 7/10 for wicking (eight patients), 9.3/10 for the double
      balloon catheter (three patients), 3.2/10 for SF (ten patients). DISCUSSION: Our
      study highlights the effectiveness of hemostatic gel matrix in the management of
      post-traumatic epistaxis compared to usual methods. It also pointed out better
      patient comfort. A prospective comparative study on a larger cohort of patient
      would support the legitimacy of SF as first-line treatment for severe
      posttraumatic epistaxis.

PMID- 24028780
TI  - Cytotoxic effects of Eryngium kotschyi and Eryngium maritimum on Hep2, HepG2,
      Vero and U138 MG cell lines.
AB  - CONTEXT: Eryngium maritimum L. and the endemic Eryngium kotschyi Boiss. of the
      Apiaceae family are used for antiinflammatory, antivenom, antinociceptive and
      diuretic purposes in folk medicine in Turkey. OBJECTIVE: This study investigated
      the cytotoxic effects of the plant extracts belonging to Eryngium L. genus on
      various cell lines. MATERIALS AND METHODS: Cytotoxic activites of the lyophilized
      aqueous aereal and root parts of the plant extracts on human hepatocellular
      carcinoma (HepG2), human laryngeal epidermoid carcinoma (Hep2), human glioma
      (U138-MG) and African green monkey kidney epithelial (Vero) cell lines at 8.33
      266.62 ug/ml concentrations were analyzed by lactate dehydrogenase (LDH) leakage
      and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) cell
      viability assays. RESULTS: Inhibitory concentration 50 (IC50) values were found
      <100 ug/ml in most cases varying around 16.33-125.66 ug/ml. IC50 values for E.
      kostchyi and E. maritimum root parts on Hep2 cells (32.86 and 30.25 ug/ml,
      respectively), E. kotschyi aereal, E. maritimum aereal and root parts on HepG2
      cells (31.75, 32.42 and 35.01 ug/ml, respectively) by MTT assay were found to be
      close to the US National Cancer Institute (NCI) recommendations (IC50 < 30 ug/ml)
      to define the antivity aganist cancer cells. The lowest IC50 values according to
      the LDH method were observed in Hep2 cells and the highest in U138-MG cells. Root
      parts were found to be more toxic than aereal parts for both plants in both
      methods in general. DISCUSSION AND CONCLUSION: Both plant extracts exerted
      cytotoxic activity aganist Hep2 and HepG2 cells, with low IC50 values defining
      their promising anticancer property according to NCI; however, further analysis
      are needed to confirm their activity.

PMID- 24028782
TI  - Myths, beliefs and fragrance allergy.

PMID- 24028783
TI  - Is 500 ppm a better concentration than 200 ppm for diagnosing contact allergy to
      methylisothiazolinone?

PMID- 24028781
TI  - VprBP (DCAF1): a promiscuous substrate recognition subunit that incorporates into
      both RING-family CRL4 and HECT-family EDD/UBR5 E3 ubiquitin ligases.
AB  - The terminal step in the ubiquitin modification system relies on an E3 ubiquitin
      ligase to facilitate transfer of ubiquitin to a protein substrate. The substrate
      recognition and ubiquitin transfer activities of the E3 ligase may be mediated by
      a single polypeptide or may rely on separate subunits. The latter organization is
      particularly prevalent among members of largest class of E3 ligases, the RING
      family, although examples of this type of arrangement have also been reported
      among members of the smaller HECT family of E3 ligases. This review describes
      recent discoveries that reveal the surprising and distinctive ability of VprBP
      (DCAF1) to serve as a substrate recognition subunit for a member of both major
      classes of E3 ligase, the RING-type CRL4 ligase and the HECT-type EDD/UBR5
      ligase. The cellular processes normally regulated by VprBP-associated E3 ligases,
      and their targeting and subversion by viral accessory proteins are also
      discussed. Taken together, these studies provide important insights and raise
      interesting new questions regarding the mechanisms that regulate or subvert VprBP
      function in the context of both the CRL4 and EDD/UBR5 E3 ligases. 

PMID- 24028784
TI  - Methylisothiazolinone in paint forces a patient out of her apartment.

PMID- 24028785
TI  - Decrease in nickel allergy in women after the second EU nickel directive.

PMID- 24028786
TI  - Contact allergy to two synthetic plastics in an orthopaedic engineer.

PMID- 24028787
TI  - Historians are from Venus, ecologists are from Mars.

PMID- 24028788
TI  - Inadvertent hypercapnia associated with anaesthesia breathing system malfunction
      in two horses.

PMID- 24028789
TI  - Initial performance evaluation of the UniCel(r) DxH slide maker/stainer
      Coulter(r) cellular analysis system.
AB  - INTRODUCTION: Despite the advancements in instrumentation within hematology
      laboratories, there is still a need for review of a peripheral blood film (PBF).
      For a thorough PBF evaluation, it is critical that a well spread and stained film
      is available. METHODS: In this study, we evaluated an automatic slide
      maker/stainer (DxH-SMS, Beckman Coulter) compared with manually prepared blood
      films on 124 normal and abnormal samples. The primary goal of the study was to
      determine whether or not the DxH-SMS was able to consistently and reproducibly
      prepare and stain blood films of exemplary quality, without carryover between
      specimens. Additionally, repeatability of white blood cell distribution,
      comparability of morphology to reference methodologies, and grading of acceptance
      criteria outlined in the CLSI document H20-A2 were assessed. RESULTS: Carryover
      was not an issue and repeatability was within expected limits. There was
      excellent agreement of the 5-part differential between the automated blood films
      made by the DxH-SMS compared with the manually prepared reference blood film.
      There was no difference in identification and enumeration of blasts, variant
      lymphocytes, or nucleated red blood cells (P < 0.05). Red cell morphology showed
      excellent agreement. CONCLUSION: Blood films prepared by the DxH-SMS are of
      excellent quality, reproducible, and compare well with manually prepared slides.
      Introduction to our laboratory has improved and standardized slide quality.

PMID- 24028790
TI  - Addressing chronic and complex conditions: what evidence is there regarding the
      role primary healthcare nurses can play?
AB  - Primary healthcare services in Australia need to respond to the needs of an
      ageing population and the rising prevalence of chronic and complex conditions in
      that population. This paper reports on the results of a comprehensive Australian
      and international literature review on nurse-led and nurse-involved primary
      healthcare interventions with a particular focus on those serving people with
      chronic and complex conditions and hard to reach populations. The key question
      this review addresses is: what role can nurses play in primary healthcare to
      manage people with chronic and complex conditions? International evidence
      demonstrates that nurses working in primary care provide effective care, have
      high patient satisfaction and patients are more likely to comply with nurse
      instructions than general practitioner instructions. Nurses can provide care
      equivalent to doctors within their scope of practice but have longer
      consultations. Lifestyle interventions provided by nurses have been shown to be
      effective for cardiac care, diabetes care, smoking cessation and obesity. The
      nursing workforce can provide appropriate, cost-effective and high-quality
      primary healthcare within their scope of practice. 

PMID- 24028791
TI  - Vector control measures failed to affect genetic structure of Aedes aegypti in a
      sentinel metropolitan area of Brazil.
AB  - In order to evaluate subpopulation differentiation, effective population size
      (Ne) and evidence for population bottlenecks at various geographic levels, Aedes
      aegypti larvae were collected longitudinally from 2007 to 2009 from four areas in
      the city of Salvador, Brazil. The DNA from each larva was isolated and genotyped
      with five independent microsatellite markers. FST and Jost's D revealed
      significant population structuring (P<0.05) at the municipal and regional levels,
      while only RST was able to detect genetic differentiation at the level of strata
      within these areas. Ne analysis from longitudinal data did not show any evidence
      of significant change in population structure. The census population measured by
      the house index, however, showed a significant trend toward decrease in these
      areas. Active vector control measures did contribute to vector reduction, but
      this was not enough to decrease A. aegypti population genetic diversity in
      Salvador. The understanding of A. aegypti population dynamics may be helpful for
      planning and evaluation of control measures to make them more effective. 

PMID- 24028792
TI  - Effects of thyroid status on NEI concentration in specific brain areas related to
      reproduction during the estrous cycle.
AB  - We previously showed that short-term hypo- and hyperthyroidism induce changes in
      neuropeptide glutamic-acid-isoleucine-amide (NEI) concentrations in discrete
      brain areas in male rats. To investigate the possible effects of hypo- and
      hyperthyroidism on NEI concentrations mainly in hypothalamic areas related to
      reproduction and behavior, female rats were sacrificed at different days of the
      estrous cycle. Circulating luteinizing hormone (LH), estradiol and progesterone
      concentrations were measured in control, hypothyroid (hypoT, treated with PTU
      during 7-9 days) and hyperthyroid (hyperT, l-T4 during 4-7 days) animals. Both
      treatments blunted the LH surge. Hypo- and hyperthyroidism increased estradiol
      concentrations during proestrus afternoon (P-PM), although hypoT rats showed
      lower values compared to control during proestrus morning (P-AM). Progesterone
      levels were higher in all groups at P-PM and in the hyperT during diestrus
      morning (D2). NEI concentrations were lower in hypoT rats during the estrous
      cycle except in estrus (E) in the peduncular part of the lateral hypothalamus
      (PLH). They were also reduced by both treatments in the perifornical part of the
      lateral hypothalamus (PeFLH) during P-PM. Hypothyroidism led to higher NEI
      concentrations during P-PM in the organum vasculosum of the lamina terminalis and
      anteroventral periventricular nucleus (OVLT+AVPV). The present results indicate
      that NEI concentration is regulated in a complex manner by hypo- and
      hyperthyroidism in the different areas studied, suggesting a correlation between
      NEI values and the variations of gonadal steroid levels during estrous cycle.
      These changes could be, in part, responsible for the alterations observed in the
      hypothalamic-pituitary-gonadal axis in these pathologies. 

PMID- 24028794
TI  - Cuticular drusen: stars in the sky.
AB  - Cuticular drusen is a specific clinical subtype of age-related macular
      degeneration (AMD). This subtype of AMD has an earlier age at onset, a stronger
      familial component, and genetic factors play a more prominent role in its
      development than in the general AMD population. In this review, we describe the
      clinical characteristics and differential diagnosis of cuticular drusen, as well
      as systemic associations including membranoproliferative glomerulonephritis type
      II. We discuss recent genetic and pathophysiological insights, and future
      therapeutic perspectives are highlighted. 

PMID- 24028793
TI  - BAIT: Organizing genomes and mapping rearrangements in single cells.
AB  - Strand-seq is a single-cell sequencing technique to finely map sister chromatid
      exchanges (SCEs) and other rearrangements. To analyze these data, we introduce
      BAIT, software which assigns templates and identifies and localizes SCEs. We
      demonstrate BAIT can refine completed reference assemblies, identifying
      approximately 21 Mb of incorrectly oriented fragments and placing over half (2.6
      Mb) of the orphan fragments in mm10/GRCm38. BAIT also stratifies scaffold-stage
      assemblies, potentially accelerating the assembling and finishing of reference
      genomes. BAIT is available at http://sourceforge.net/projects/bait/. 

PMID- 24028796
TI  - Thymic stromal lymphopoietin suppresses the apoptosis of decidual gamma-delta T
      cells via regulation of the signal transduction and activation of transcription
      3/caspase-3 signaling pathway.
AB  - PROBLEM: To investigate whether thymic stromal lymphopoietin (TSLP) regulates the
      apoptosis of decidual gammadelta T cells and to elucidate the mechanism. METHOD
      OF STUDY: Primary human decidual gammadelta T cells were treated with TSLP only
      or TSLP combined with different signaling inhibitors (STAT3, STAT5, AKT, and
      ERK). The levels of signal transduction and activation of transcription 3 (STAT3)
      tyrosine phosphorylation and caspase3 expression were determined using Western
      blot analysis, and the apoptosis of decidual gammadelta T cells was analyzed by
      flow cytometry. RESULTS: The proportions of gammadelta T cells in the peripheral
      circulation and in decidual CD3(+) cell population in women with normal pregnancy
      were higher than the proportions of gammadelta T cells in either non-pregnant
      control or miscarriage. Decidual gammadelta T cells co-expressed the TSLP
      receptors (TSLPR) and IL-7Ralpha, and the expression of TSLPR in decidual
      gammadelta T cells was higher than that in decidual CD8(+) and CD4(+) T cells.
      Treatment with TSLP significantly suppressed the apoptosis of decidual gammadelta
      T cells and enhanced STAT3 phosphorylation. Moreover, STAT3, and not other
      inhibitors, completely abrogated the anti-apoptotic effect and expression of
      caspase3 in decidual gammadelta T cells induced by recombinant human TSLP.
      CONCLUSION: These results suggest that TSLP may down-regulate caspase3 expression
      through activation of the STAT3 pathway, thereby suppressing the apoptosis of
      decidual gammadelta T cells.

PMID- 24028795
TI  - Prospective neurochemical characterization of child offspring of parents with
      bipolar disorder.
AB  - We wished to determine whether decreases in N-acetyl aspartate (NAA) and
      increases in myoinositol (mI) concentrations as a ratio of creatine (Cr) occurred
      in the dorsolateral prefrontal cortex (DLPFC) of pediatric offspring of parents
      with bipolar disorder (BD) and a healthy comparison group (HC) over a 5-year
      period using proton magnetic resonance spectroscopy ((1)H-MRS). Paticipants
      comprised 64 offspring (9-18 years old) of parents with BD (36 with established
      BD, and 28 offspring with symptoms subsyndromal to mania) and 28 HCs, who were
      examined for group differences in NAA/Cr and mI/Cr in the DLPFC at baseline and
      follow-up at either 8, 10, 12, 52, 104, 156, 208, or 260 weeks. No significant
      group differences were found in metabolite concentrations at baseline or over
      time. At baseline, BD offspring had trends for higher mI/Cr concentrations in the
      right DLPFC than the HC group. mI/Cr concentrations increased with age, but no
      statistically significant group differences were found between groups on follow
      up. It may be the case that with intervention youth at risk for BD are
      normalizing otherwise potentially aberrant neurochemical trajectories in the
      DLPFC. A longer period of follow-up may be required before observing any group
      differences. 

PMID- 24028797
TI  - Fractional dynamical model for the generation of ECG like signals from filtered
      coupled Van-der Pol oscillators.
AB  - In this paper, an incommensurate fractional order (FO) model has been proposed to
      generate ECG like waveforms. Earlier investigation of ECG like waveform
      generation is based on two identical Van-der Pol (VdP) family of oscillators,
      which are coupled by time delays and gains. In this paper, we suitably modify the
      three state equations corresponding to the nonlinear cross-product of states,
      time delay coupling of the two oscillators and low-pass filtering, using the
      concept of fractional derivatives. Our results show that a wide variety of ECG
      like waveforms can be simulated from the proposed generalized models,
      characterizing heart conditions under different physiological conditions. Such
      generalization of the modelling of ECG waveforms may be useful to understand the
      physiological process behind ECG signal generation in normal and abnormal heart
      conditions. Along with the proposed FO models, an optimization based approach is
      also presented to estimate the VdP oscillator parameters for representing a
      realistic ECG like signal. 

PMID- 24028798
TI  - An automatic algorithm for the detection of Trypanosoma cruzi parasites in blood
      sample images.
AB  - Chagas disease is a tropical parasitic disease caused by the flagellate protozoan
      Trypanosoma cruzi (T. cruzi) and currently affecting large portions of the
      Americas. One of the standard laboratory methods to determine the presence of the
      parasite is by direct visualization in blood smears stained with some colorant.
      This method is time-consuming, requires trained microscopists and is prone to
      human mistakes. In this article we propose a novel algorithm for the automatic
      detection of T. cruzi parasites, in microscope digital images obtained from
      peripheral blood smears treated with Wright's stain. Our algorithm achieved a
      sensitivity of 0.98 and specificity of 0.85 when evaluated against a dataset of
      120 test images. Experimental results show the versatility of the method for
      parasitemia determination. 

PMID- 24028799
TI  - The safety of UK video telemetry units: results of a national service evaluation.
AB  - PURPOSE: To assess patient safety during seizures occurring on UK video telemetry
      units and identify factors in unit infrastructure which may improve safety with
      the intention of producing national guidelines. METHODS: A prospective
      multicentre national service evaluation of the occurrence of adverse events and
      level of nurse attendance during seizures occurring on video telemetry units was
      performed. Data from 272 seizures from 27 video telemetry units across the UK
      were analysed. RESULTS: Adverse events occurred in 12% of seizures: 7% were
      physical events such as falls or respiratory compromise and 5% were unnoticed
      seizures. Nursing staff did not attend the patients in 44% of seizures and
      attendance was delayed beyond 30s in a further 29%. Only 27% of seizures were
      attended by a Healthcare Professional within half a minute. The most important
      factor shown to improve timely attendance of patients during seizures was the
      presence of a nurse dedicated to the telemetry bed(s). The site of the telemetry
      bed (bay or cubicle) and method of observation (direct or indirect) was less
      important. An optimal nurse-to-patient ratio was difficult to identify but the
      study suggests that a ratio of at least 1 nurse to 4 patients is appropriate.
      CONCLUSION: The results provide an evidence base for the production of national
      standards and guidelines for surveillance of patients during video telemetry to
      improve patient safety.

PMID- 24028800
TI  - Relationships between trace element concentrations in chorionic tissue of
      placenta and umbilical cord tissue: potential use as indicators for prenatal
      exposure.
AB  - The role of the placenta was assessed by comparing the profiles of methylmercury
      (MeHg), inorganic mercury (I-Hg), lead (Pb), cadmium (Cd), selenium (Se), zinc
      (Zn), and copper (Cu) in freeze-dried chorionic tissue of the placenta and
      umbilical cord tissue. The significance of the placenta and cord tissue as
      predictors of prenatal exposure to these trace elements in pregnant women and
      newborns was also examined by comparing the element profiles among placenta and
      cord tissue, and maternal and cord blood red blood cells (RBCs). The samples were
      collected from 48 mother-child pairs at birth in the general population of
      Japanese. The concentrations of all elements, except for MeHg, were significantly
      higher in placenta than in cord tissue. In particular, the Cd showed the highest
      placenta vs. cord tissue ratio (59:1), followed by I-Hg (2.4:1), indicating that
      the placental barrier works most strongly against Cd among the examined toxic
      elements. Contrary to the other elements, the MeHg concentration in cord tissue
      was significantly higher (1.6 times) than that in placenta, indicating its
      exceptionally high placental transfer. The MeHg in placenta showed significant
      correlations with total mercury (T-Hg) in maternal and cord RBCs (rs=0.80 and
      0.91, respectively). The MeHg in cord tissue also showed significant correlations
      with T-Hg in maternal and cord RBCs (rs=0.75 and 0.85, respectively). Therefore,
      both placenta and cord tissue are useful for predicting maternal and fetal
      exposure to MeHg. The Se concentration in placenta showed significant but
      moderate correlations with that in maternal and cord RBCs (rs=0.38 and 0.57,
      respectively). The Pb, Zn, and Cu concentrations in placenta and cord tissue
      showed no significant correlations with those in maternal and cord RBCs. As an
      exception, the Cd concentration in placenta showed a moderate but significant
      correlation (rs=0.41) with that in maternal RBCs, suggesting that the placenta is
      useful for predicting maternal exposure to Cd during gestation. 

PMID- 24028803
TI  - Guest editorial.

PMID- 24028802
TI  - Efficacy of ketamine hydrochloride administered as a basilar sesamoid nerve block
      in alleviating foot pain in horses caused by natural disease.
AB  - REASONS FOR PERFORMING STUDY: A local anaesthetic agent capable of temporarily
      resolving lameness after being administered perineurally would be helpful because
      rapid return of lameness would allow for other analgesic techniques to be
      performed within a short period of time. OBJECTIVES: To determine if a 3%
      solution of ketamine hydrochloride (HCl), administered around the palmar nerves
      at the level of the base of the proximal sesamoid bones, can improve naturally
      occurring lameness that can be improved or abolished with a basilar sesamoid
      nerve block performed using lidocaine HCl and to compare the change in gait
      produced using lidocaine to the change in gait produced using ketamine by using
      objective lameness assessment. STUDY DESIGN: Experimental trial using research
      horses with naturally occurring lameness. METHODS: Seven horses, chronically lame
      on a thoracic limb, were chosen for the study. A wireless, inertial, sensor
      based, motion analysis system was used to evaluate lameness before and after
      administration of 2% lidocaine and later, before and after administration of 3%
      ketamine over the palmar digital nerves at the base of the proximal sesamoid
      bones (a basilar sesamoid nerve block) at 5 min intervals for 30 min. Lameness
      scores obtained before and after administration of lidocaine and ketamine HCl
      were compared using repeated measures analysis. RESULTS: Gait significantly
      improved after basilar sesamoid nerve blocks using 2% lidocaine, but gait did not
      significantly improve after performing the same nerve block using 3% ketamine
      HCl. CONCLUSIONS: Ketamine (3%) administered perineurally for regional
      anaesthesia of the digit does not desensitise the digit to the same extent as
      does lidocaine and thus 3% ketamine appears to have no value as a local
      anaesthetic agent for diagnostic regional anaesthesia.

PMID- 24028801
TI  - Low frequency repetitive transcranial magnetic stimulation of the left
      dorsolateral prefrontal cortex transiently increases cue-induced craving for
      methamphetamine: a preliminary study.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) can temporarily
      interrupt or facilitate activity in a focal brain region. Several lines of
      evidence suggest that rTMS of the dorsolateral prefrontal cortex (DLPFC) can
      affect processes involved in drug addiction. We hypothesized that a single
      session of low-frequency rTMS of the left DLPFC would modulate cue-induced
      craving for methamphetamine (MA) when compared to a sham rTMS session. METHODS:
      In this single-blind, sham-controlled crossover study, 10 non-treatment seeking
      MA-dependent users and 8 healthy controls were randomized to receive 15 min of
      sham and real (1 Hz) DLPFC rTMS in two experimental sessions separated by 1h.
      During each rTMS session, participants were exposed to blocks of neutral cues and
      MA-associated cues. Participants rated their craving after each cue block.
      RESULTS: In MA users, real rTMS over the left DLPFC increased self-reported
      craving as compared to sham stimulation (17.86 +/- 1.46 vs. 24.85 +/- 1.57,
      p=0.001). rTMS had no effect on craving in healthy controls. One Hertz rTMS of
      the left DLPFC was safe and tolerable for all participants. CONCLUSIONS: Low
      frequency rTMS of the left DLPFC transiently increased cue-induced craving in MA
      participants. These preliminary results suggest that 1 Hz rTMS of the left DLPFC
      may increase craving by inhibiting the prefrontal cortex or indirectly activating
      subcortical regions involved in craving.

PMID- 24028804
TI  - Effect of nanosilica and silicon sources on plant growth promoting rhizobacteria,
      soil nutrients and maize seed germination.
AB  - The study was aimed at evaluating the effect of nanosilica and different sources
      of silicon on soil properties, total bacterial population and maize seed
      germination. Nanosilica was synthesised using rice husk and characterised. Silica
      powder was amorphous (50 nm) with >99.9% purity. Sodium silicate treated soil
      inhibited plant growth promoting rhizobacteria in contrast to nanosilica and
      other bulk sources. Surface property and effect of soil nutrient content of
      nanosilica treatment were improved. Colony forming unit (CFU) was doubled in the
      presence of nanosilica from 4 * 105 CFU (control) to 8 * 105 CFU per gram of
      soil. The silica and protein content of bacterial biomass clearly showed an
      increase in uptake of silica with an increase in nanosilica concentration.
      Nanosilica promoted seed germination percentage (100%) in maize than conventional
      Si sources. These studies show that nanosilica has favourable effect on
      beneficial bacterial population and nutrient value of soil. 

PMID- 24028805
TI  - Evaluation of therapeutic potential of nanosilver particles synthesised using
      aloin in experimental murine mastitis model.
AB  - Nanobiotechnology is an emerging biological branch of nanotechnology. Application
      of nanoparticles with specific size and shape in biology has already shown
      unforeseen and interesting results. A study was conducted to evaluate the
      therapeutic potential of phytogenically derived aloin mediated nanosilver
      particles (AAgNPs), prepared by reduction of silver nitrate with aloin, in
      Staphylococcus aureus induced murine mastitis. A total of 40 female mice were
      divided into five groups of eight animals each. Group I served as lactating
      control, groups II-V were inoculated with 20 MUl of 24 h broth culture of S.
      aureus containing 4.0 * 105 cfu/quarter under ketamine anaesthesia. After 6 h
      post inoculation, groups III and IV received 20 MUl of aloin nanosilver (AAgNPs)
      through intramammary and intraperitoneal routes, respectively. Group V received
      antibiotic cefepime at 1 mg/kg body weight through the intra-peritoneal route.
      After 18 h post-treatment, serum C reactive protein, weights of mammary glands,
      mammary gland bacterial load, thiobarbituric acid reactive substances content,
      reduced glutathione content, superoxide dismutase activity and catalase activity
      and histopathology were determined. The compound showed a minimum inhibitory
      concentration of 21.8 ng/ml against S. aureus. Significant reduction (98%) in
      poly-morpho nuclear cell infiltration was observed with AAgNPs than antibiotic
      (50%). 

PMID- 24028806
TI  - Biosynthesis of silver nanoparticles by the seed extract of Strychnos potatorum:
      a natural phytocoagulant.
AB  - In this study, facile and ecofriendly methods have been developed for the
      biosynthesis of silver nanoparticles from silver nitrate using the seed extract
      of Strychnos potatorum, a natural phytocoagulant. The effect of room temperature
      stirring, water bath heating and autoclaving on nanoparticle synthesis was
      studied. The water soluble compounds in the extract serve as reducing and
      stabilising agents. Analytical techniques such as UV-visible spectroscopy,
      transmission electron microscopy (TEM) and X-ray diffraction were used to
      characterise the synthesised nanoparticles. By tuning the reaction conditions,
      size controlled spherical nanoparticles of around 14.1 +/- 4.8 nm were generated.
      The face centred cubic crystalline structure of the nanoparticles is confirmed
      from the observed peaks corresponding to (111), (200), (220) and (311) planes in
      the XRD pattern, concentric rings with intermittent bright dots in selected-area
      electron diffraction patterns and clear lattice fringes in high-resolution TEM
      images. With Fourier transform infrared spectroscopy and Raman spectroscopy, a
      probable mechanism involved in the reduction and stabilisation of nanoparticles
      has been investigated. As the silver nanoparticles are encapsulated with
      functional groups, they can be easily integrated for various biomedical
      applications. 

PMID- 24028807
TI  - Biogenic synthesis of nanostructured iron compounds: applications and
      perspectives.
AB  - 'Green nanotechnology' has attracted increasing attention in recent years because
      of the possibility to reduce and/or eliminate toxic substances. Indeed, biogenic
      syntheses of nanomaterials, such as nanoparticles (NPs), are considered economic
      and valuable alternatives for the production of metallic NPs for diverse
      applications. Recent studies have revealed that the development of eco-friendly
      technologies in material science is under extensive investigation in the field of
      nanobiotechnology. Considering this scenario, this review highlights the recent
      advances in the biogenic syntheses of metallic iron, iron sulphides and iron
      oxide NPs for a wide range of applications. Moreover, this review also discusses
      the medical, environmental and technological applications of biogenically
      synthesised NPs, and the challenges to be faced to optimise the eco-friendly
      production of these important nanomaterials. 

PMID- 24028808
TI  - Immobilisation of lipase on the surface of magnetic nanoparticles and non-porous
      glass beads for regioselective acetylation of prednisolone.
AB  - Magnetic nanoparticles (MNPs) were prepared by co-precipitation of Fe+3/Fe+2
      (2:1; molar ratio) with a mean size of 40 +/- 5 nm. Scanning electron microscopy,
      dynamic light scattering, X-ray diffraction, vibrating sample magnetometer and
      thermogravimetric analysis were used to characterise the MNPs. The MNPs and also
      hydroxylated nonporous glass beads were similarly functionalised with the aid of
      glutaraldehyde to be cross-linked to lipase originated from Thermomyces
      lanuginosus (TLL). The yield and efficiency for immobilised lipase on the MNPs
      were calculated as 72 +/- 2.4 and 63 +/- 3.5%, whereas a yield and efficiency of
      60 +/- 2.1 and 55 +/- 4.1%, respectively, were measured for the corresponding
      parameters of the immobilised enzyme on the glass beads. When the immobilised TLL
      was compared with its free form, Michaelis-Menten kinetics indicated an
      insignificant change in the Michaelis constant (Km) and a drastic decrease in the
      maximum substrate conversion rate (Vmax). The immobilised TLL and six other
      commercial lipases were then checked for regioselective acetylation of
      prednisolone. The highest and lowest yields of the product were observed for
      Novozym 435 and immobilised TLL on the glass beads, respectively. Immobilised TLL
      retained its bioacetylation activity of prednisolone in five successive catalytic
      processes.

PMID- 24028809
TI  - Biological synthesis of metallic nanoparticles using algae.
AB  - The increasing demand and limited natural resources of noble metals make its
      recovery from dilute industrial wastes attractive, especially when using
      environmentally friendly methods. Nowadays, the high impact that nanotechnology
      is having in both science and society offers new research possibilities. Gold and
      silver nanoparticles were biosynthesised by a simple method using different algae
      as reducing agent. The authors explored the application of dead algae in an eco
      friendly procedure. The nanoparticle formation was followed by UV-vis absorption
      spectroscopy and transmission electron microscopy. The functional groups involved
      in the bioreduction were studied by Fourier transform infrared spectroscopy. 

PMID- 24028810
TI  - Plants as potential synthesiser of precious metal nanoparticles: progress and
      prospects.
AB  - The synthesis of metal nanoparticles is an active area of research in the field
      of nanotechnology. A variety of chemical and physical methods are used for
      synthesis of nanoparticles. However, these methods suffer from many drawbacks
      including use of toxic solvents, high energy consumption, hazardous by products
      etc. Hence, there is an essential need to develop environment-friendly methods
      for synthesis of metal nanoparticles. A promising approach to overcome this need
      is to harness the biological sources for synthesis of metal nanoparticles. Over
      the past several years, plants and their different products have come up as a low
      cost, energy-efficient and non-toxic approach for synthesis of metal
      nanoparticles. In the present review, the authors provide an overview of various
      reports of the synthesis of metal nanoparticles by plants, the progress and
      future prospects of this field. 

PMID- 24028811
TI  - [Lyme arthritis in children: a diagnostic trap].
AB  - Lyme disease incidence is diverse in France. It is rare in many regions but very
      frequent in Central and Eastern France. Arthritis is a late manifestation of Lyme
      disease. In children, the clinical and biological picture often resembles that of
      septic arthritis and juvenile rheumatoid arthritis, which are more frequent. This
      explains why diagnosis may be delayed, especially when patient lives in a region
      of low incidence. We report the case of an 8-year old girl with knee arthritis
      treated as septic arthritis in a region where Lyme disease is rare. Six days
      later, clinical and biological worsening suggested that the diagnosis had to be
      reconsidered. Lyme arthritis was confirmed by serology. Treatment was adapted and
      the progression was positive. This case reminds us that, in children, Lyme
      arthritis may look alike septic arthritis or juvenile rheumatoid arthritis and
      must be considered as a possible diagnosis, even in low-incidence areas. 

PMID- 24028812
TI  - Low-toxicity treatment for colorectal cancer in elderly people.

PMID- 24028814
TI  - The stratification of gastric cancer risk in Latin America.

PMID- 24028813
TI  - Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with
      previously untreated metastatic colorectal cancer (AVEX): an open-label,
      randomised phase 3 trial.
AB  - BACKGROUND: Elderly patients are often under-represented in clinical trials of
      metastatic colorectal cancer. We aimed to assess the efficacy and safety of
      bevacizumab plus capecitabine compared with capecitabine alone in elderly
      patients with metastatic colorectal cancer. METHODS: For this open-label,
      randomised phase 3 trial, patients aged 70 years and older with previously
      untreated, unresectable, metastatic colorectal cancer, who were not deemed to be
      candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were
      randomly assigned in a 1:1 ratio via an interactive voice-response system,
      stratified by performance status and geographical region. Treatment consisted of
      capecitabine (1000 mg/m(2) orally twice a day on days 1-14) alone or with
      bevacizumab (7.5 mg/kg intravenously on day 1), given every 3 weeks until disease
      progression, unacceptable toxic effects, or withdrawal of consent. Efficacy
      analyses were based on the intention-to-treat population. The primary endpoint
      was progression-free survival. The trial is registered with ClinicalTrials.gov,
      number NCT00484939. FINDINGS: From July 9, 2007, to Dec 14, 2010, 280 patients
      with a median age of 76 years (range 70-87) were recruited from 40 sites across
      ten countries. Patients were randomly assigned to receive either bevacizumab plus
      capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was
      significantly longer with bevacizumab and capecitabine than with capecitabine
      alone (median 9.1 months [95% CI 7.3-11.4] vs 5.1 months [4.2-6.3]; hazard ratio
      0.53 [0.41-0.69]; p<0.0001). Treatment-related adverse events of grade 3 or worse
      occurred in 53 (40%) patients in the combination group and 30 (22%) in the
      capecitabine group, and treatment-related serious adverse events in 19 (14%) and
      11 (8%) patients. The most common grade 3 or worse adverse events of special
      interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16%] vs
      nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events
      (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the
      combination group and four in the capecitabine group. The most common any-grade
      adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs
      nine [7%]). INTERPRETATION: The combination of bevacizumab and capecitabine is an
      effective and well-tolerated regimen for elderly patients with metastatic
      colorectal cancer. FUNDING: F Hoffmann-La Roche.

PMID- 24028815
TI  - Timing of fusion of the ischiopubic ramus from dry bone observations.
AB  - There is little information about the age at which the ischiopubic ramus fuses
      derived from dry bone observations. This study documents the age ranges for union
      of the ischiopubic ramus in a sample of 148 known sex and age skeletons from
      Portugal, with ages ranging from birth to 20 years, using a three-stage scheme.
      The oldest female with an unfused ramus is 11 years old and the oldest male is 8
      years old. The youngest male with a completely fused ramus is 7 years old, and
      the youngest female is 5 years old. Despite the relatively large sample size,
      partial fusion was a rare event to record as only two individuals were at this
      stage and these seemed relatively older than expected (12 and 14 years of age).
      The likely age interval for partial union of the ramus was subsequently estimated
      from logistic regression, for both sexes separated and combined. In the sex
      pooled sample, the inter-quartile range (25th-75th percentile) for the median age
      of fusion is 7-11 years and the 10th-90th percentile range is 4-15 years. The
      scarcity of data on the age of ischiopubic fusion may be related to biases in the
      sample or to fusion occurring rapidly in this anatomical location. Additional
      studies may be required to assess the accuracy of the ages reported here, but at
      present this study provides the most comprehensive assessment of timing of fusion
      at the ischiopubic ramus from observations of dry bone specimens.

PMID- 24028816
TI  - Subsistence strategy changes: the evidence of entheseal changes.
AB  - Changes in subsistence strategy have caused some of the profoundest changes to
      the structure and health of humans. This study aims to test whether these changes
      have reduced work-load as assessed by entheseal changes. Entheseal changes,
      formerly called musculoskeletal stress markers, are thought to reflect muscle
      usage throughout life, although it is widely agreed that they have a
      multifactorial origin. This paper uses a meta-analysis of comparable published
      data to plot trends in time by muscle, enthesis type and sex. The results show
      that agriculturalists have the lowest scores for entheseal changes, with hunte
      gatherers next highest and those working in industry the highest. These findings
      are the same for males and females, for most muscles and muscle groups. However,
      entheseal changes are highly correlated with increased age and the age
      distributions of the samples analysed could not be compared. It is, therefore,
      possible that differences in age distribution of the samples are one of the
      reasons for this finding. Recommendations are provided to reduce this and other
      limitations for future meta-analyses.

PMID- 24028817
TI  - Cortical bone thickness can adapt locally to muscular loading while changing with
      age.
AB  - Mechanical loading of muscle action is concentrated at muscle attachment sites;
      thus there may be a potential for site-specific variation in cortical bone
      thickness. Humeri from an early 20th-century Finnish (Helsinki) and two medieval
      English (Newcastle, Blackgate and York, Barbican) populations were subjected to
      pQCT scanning to calculate site-specific cross-sectional cortical bone area (CA)
      for four locations and to measure cortical thickness at muscle attachment sites
      and non-attachment sites. We found that CA at 80% of humerus length was
      significantly reduced compared to more distal cross-sections, which can be due to
      reduced stresses at the proximal shaft. The principal direction of loading at 80%
      humerus length was towards mediolateral plane, likely due to fixing the humerus
      close to the torso. At 35% the main direction of loading was towards
      anteroposterior plane, reflecting elbow flexing forces. The principal direction
      of loading varied between populations, sides and sexes at 50% humerus length due
      to preference between elbow and shoulder joint; thus this location might be
      useful when trying to infer differences in activity. These changes are likely due
      to overall shaft adaptation to forces acting at the humerus. In addition, we
      found a potential for site-specific variation in cortical thickness; cortical
      bone at muscle attachment sites was significantly thicker compared to non
      attachment sites. Lastly, CA at 35% of humerus length and cortical thickness at
      non-attachment sites decreased with age. These results underline the importance
      of muscle loading for bone mass preservation as well as indicate that a site
      specific variation of bone mass is possible.

PMID- 24028818
TI  - Systemic use of non-biologic agents in orofacial diseases: other immunomodulatory
      agents.
AB  - Systemic non-biologic agents have long been in clinical use in medicine--often
      with considerable efficacy, albeit with some adverse effects--as with all
      medications. With the advent of biologic agents, all of which currently are
      restricted to systemic use, there is a growing need to ensure which agents have
      the better therapeutic ratio. The non-biologic agents (NBAs) include a range of
      agents, most importantly the corticosteroids (steroids). Previous articles by us
      in this series have discussed systemic use of corticosteroids and purine
      synthesis inhibitors; the other immunomodulating agents (calcineurin inhibitors,
      thalidomide, dapsone, colchicine and cyclophosphamide) are reviewed in this final
      article.

PMID- 24028819
TI  - [Update on the use of PET radiopharmaceuticals in inflammatory disease].
AB  - The use of molecular imaging with PET/CT technology using different radiotracers,
      especially the (18)F-FDG is currently spreading beyond the area of oncology, the
      most interest being placed on inflammatory and infectious diseases. This article
      presents a review of its contribution in different inflammatory conditions in the
      context of structural and conventional nuclear medicine imaging. Special emphasis
      is placed on the more significant diseases such as large-vessel vasculitis,
      sarcoidosis, rheumatoid arthritis and inflammatory bowel disease and the study of
      the atheroma plaque. 

PMID- 24028820
TI  - Lipopolysaccharide neutralization by a novel peptide derived from phosvitin.
AB  - Lipopolysaccharide (LPS), also known as endotoxin, is the primary trigger of
      sepsis, which is associated with high mortality in patients. No therapeutic
      agents are currently efficacious enough to protect patients from sepsis
      characterized by LPS-mediated tissue damage and organ failure. Previously, a
      phosvitin-derived peptide, Pt5, which consists of the C-terminal 55 residues of
      zebrafish phosvitin, has been shown to function as an antibacterial agent. In
      this study, we have generated six mutants by site-directed mutagenesis based on
      the sequence of Pt5, and found that one of the six mutants, Pt5e, showed the
      strongest bactericidal activities against Escherichia coli and Staphylococcus
      aureus. We then demonstrated that Pt5e was able to bind to LPS and lipoteichoic
      acid (LTA). More importantly, we showed that Pt5e significantly inhibited LPS
      induced tumor-necrosis factor (TNF)-alpha and interleukin (IL)-1beta release from
      murine RAW264.7 cells and considerably reduced serum TNF-alpha and IL-1beta
      levels in mice. Additionally, Pt5e protected the liver from damage by LPS, and
      remarkably promoted the survival rate of the endotoxemia mice. Furthermore, Pt5e
      displayed no cytotoxicity to murine RAW264.7 macrophages and no hemolytic
      activity toward human red blood cells. These data together indicate that Pt5e is
      an endotoxin-neutralizing agent with a therapeutic potential in clinical
      treatment of LPS-induced sepsis. 

PMID- 24028821
TI  - FoxO regulates expression of ABCA6, an intracellular ATP-binding-cassette
      transporter responsive to cholesterol.
AB  - ATP-binding-cassette (ABC) proteins have been recognized as key players in
      cellular physiological transport processes. ABC transporter A6 (ABCA6) is a
      member of the ABC subfamily A. Although it was cloned more than 10 years ago, its
      expression regulation, subcellular localization, and physiologic function remain
      largely unknown. We here demonstrated that expression of ABCA6 was Forkhead box O
      (FoxO)-dependent in human endothelial cell line EA.hy926 and human umbilical vein
      endothelial cells. Two functional FoxO-responsive elements were identified in
      ABCA6 promoter and characterized in detail. ABCA6 mRNA was suppressed by insulin
      like growth factor-1 which stimulates the phosphorylation and inactivation of
      FoxOs while inhibitor of phosphatidylinositol 3-kinase had the opposite effect.
      By immunofluorescence and confocal microscopy, ABCA6 protein is localized
      primarily in an intracellular compartment, likely representing the Golgi
      apparatus. ABCA6 mRNA was demonstrated to be responsive to cholesterol loading as
      well as 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors in human
      endothelial cells. Our data provide evidence for an essential role of FoxO
      proteins in the transcription of ABCA6 in human vascular endothelial cells. Based
      on its cholesterol responsiveness, a potential involvement of ABCA6 in
      intracellular lipid transport processes may be anticipated. 

PMID- 24028822
TI  - Growth factor gene expression profiles of bone morphogenetic protein-2-treated
      human adipose stem cells seeded on calcium phosphate scaffolds in vitro.
AB  - The secretome of stem cells strongly determines the outcome of tissue engineering
      strategies. We investigated how the secretome of human adipose stem cells (hASCs)
      can be affected by substrate, BMP-2 treatment, and degree of differentiation. We
      hypothesized that as differentiation progresses, hASCs produce increasingly more
      gene products associated with processes such as angiogenesis and bone remodeling.
      Human ASCs were treated for 15 min with BMP-2 (10 ng/ml) to enhance osteogenic
      differentiation, or with vehicle. Subsequently, hASCs were seeded on plastic or
      on biphasic calcium phosphate (BCP) consisting of 60% hydroxyapatite and 40% beta
      tricalcium phosphate. A PCR array for ~150 trophic factors and differentiation
      related genes was performed at day 21 of culture. A limited set of factors was
      quantified by qPCR at days 0, 4, 14 and 21, and/or ELISA at day 21. Compared to
      plastic, BCP-cultured hASCs showed >=2-fold higher expression of ~20 factors,
      e.g. cytokines such as IL-6, growth factors such as FGF7 and adhesion molecules
      such as VCAM1. Expression of another ~50 genes was decreased >=2-fold on BCP vs.
      plastic, even though hASCs differentiate better on BCP than on plastic. BMP-2
      treatment increased the expression of ~30 factors by hASCs seeded on BCP, while
      it decreased the expression of only PGF, PPARG and PTN. Substrate affected hASC
      secretion of Activin A and seemed to affect P1NP release. No clear association
      between hASC osteogenic differentiation and growth factor expression pattern was
      observed. Considering our observed lack of association between the degree of
      differentiation and the expression of factors associated with angiogenesis and
      bone remodeling by hASCs, future bone regeneration studies should focus more on
      systematically orchestrating the secretome of stem cells, rather than on inducing
      osteogenic differentiation of stem cells only. Short incubation with BMP-2 may be
      a promising treatment to enhance both osteogenic differentiation and
      environmental modulation.

PMID- 24028823
TI  - Human mitochondrial NDUFS3 protein bearing Leigh syndrome mutation is more prone
      to aggregation than its wild-type.
AB  - NDUFS3 is an integral subunit of the Q module of the mitochondrial respiratory
      Complex-I. The combined mutation (T145I + R199W) in the subunit is reported to
      cause optic atrophy and Leigh syndrome accompanied by severe Complex-I
      deficiency. In the present study, we have cloned and overexpressed the human
      NDUFS3 subunit and its double mutant in a soluble form in Escherichia coli. The
      wild-type (w-t) and mutant proteins were purified to homogeneity through a serial
      two-step chromatographic purification procedure of anion exchange followed by
      size exclusion chromatography. The integrity and purity of the purified proteins
      was confirmed by Western blot analysis and MALDI-TOF/TOF. The conformational
      transitions of the purified subunits were studied through steady state as well as
      time resolved fluorescence and CD spectroscopy under various denaturing
      conditions. The mutant protein showed altered polarity around tryptophan
      residues, changed quenching parameters and also noticeably altered secondary and
      tertiary structure compared to the w-t protein. Mutant also exhibited a higher
      tendency than the w-t protein for aggregation which was examined using
      fluorescent (Thioflavin-T) and spectroscopic (Congo red) dye binding techniques.
      The pH stability of the w-t and mutant proteins varied at extreme acidic pH and
      the molten globule like structure of w-t at pH1 was absent in case of the mutant
      protein. Both the w-t and mutant proteins showed multi-step thermal and Gdn-HCl
      induced unfolding. Thus, the results provide insight into the alterations of
      NDUFS3 protein structure caused by the mutations, affecting the overall integrity
      of the protein and finally leading to disruption of Complex-I assembly.

PMID- 24028824
TI  - Phased searching with NEAT in a time-scaled framework: experiments on a computer
      aided detection system for lung nodules.
AB  - OBJECTIVE: In the field of computer-aided detection (CAD) systems for lung
      nodules in computed tomography (CT) scans, many image features are presented and
      many artificial neural network (ANN) classifiers with various structural
      topologies are analyzed; frequently, the classifier topologies are selected by
      trial-and-error experiments. To avoid these trial and error approaches, we
      present a novel classifier that evolves ANNs using genetic algorithms, called
      "Phased Searching with NEAT in a Time or Generation-Scaled Framework",
      integrating feature selection with the classification task. METHODS AND
      MATERIALS: We analyzed our method's performance on 360 CT scans from the public
      Lung Image Database Consortium database. We compare our method's performance with
      other more-established classifiers, namely regular NEAT, Feature-Deselective NEAT
      (FD-NEAT), fixed-topology ANNs, and support vector machines (SVMs) using ten-fold
      cross-validation experiments of all 360 scans. RESULTS: The results show that the
      proposed "Phased Searching" method performs better and faster than regular NEAT,
      better than FD-NEAT, and achieves sensitivities at 3 and 4 false positives (FP)
      per scan that are comparable with the fixed-topology ANN and SVM classifiers, but
      with fewer input features. It achieves a detection sensitivity of 83.0+/-9.7%
      with an average of 4FP/scan, for nodules with a diameter greater than or equal to
      3mm. It also evolves networks with shorter evolution times and with lower
      complexities than regular NEAT (p=0.026 and p<0.001, respectively). Analysis on
      the average and best network complexities evolved by regular NEAT and by our
      approach shows that our approach searches for good solutions in lower dimensional
      search spaces, and evolves networks without superfluous structure. CONCLUSIONS:
      We have presented a novel approach that combines feature selection with the
      evolution of ANN topology and weights. Compared with the original threshold-based
      Phased Searching method of Green, our method requires fewer parameters and
      converges to the optimal network complexity required for the classification task
      at hand. The results of the ten-fold cross-validation experiments also show that
      our proposed CAD system for lung nodule detection performs well with respect to
      other methods in the literature.

PMID- 24028825
TI  - New predictive marker for hemodialysis vascular access dysfunction.
AB  - To examine the relationship between intra-access pressures and vascular stenosis,
      we measured the total (pT ) and static (pS ) pressures and the severity of
      stenosis before and after percutaneous transluminal angioplasty (PTA). The
      dynamic pressure (?p) and static intra-access pressure ratios (SIAPR) were
      calculated. We analyzed the clinical correlation of ?p and SIAPR with the
      severity and location of stenosis, and searched potential predictive factors for
      the severity of stenosis using multivariate regression. While SIAPR was
      significantly decreased only in outflow stenosis after PTA (p < 0.0001), ?p was
      significantly increased in both inflow and in outflow stenosis (p < 0.05). SIAPR
      was negatively correlated with the severity of stenosis only in outflow stenosis
      (p < 0.0001), and ?p was significantly correlated with both inflow and outflow
      stenosis (p < 0.05). ?p was an independent predictor for the severity of stenosis
      in both inflow and outflow stenosis (p < 0.05). Thus, our study suggests that ?p
      may be more clinically useful than SIAPR not only in detecting access stenosis
      regardless of its location, but also providing information about the severity of
      stenosis. 

PMID- 24028827
TI  - Membrane channels as integrators of G-protein-mediated signaling.
AB  - A variety of extracellular stimuli regulate cellular responses via membrane
      receptors. A well-known group of seven-transmembrane domain-containing proteins
      referred to as G protein-coupled receptors, directly couple with the
      intracellular GTP-binding proteins (G proteins) across cell membranes and trigger
      various cellular responses by regulating the activity of several enzymes as well
      as ion channels. Many specific populations of ion channels are directly
      controlled by G proteins; however, indirect modulation of some channels by G
      protein-dependent phosphorylation events and lipid metabolism is also observed. G
      protein-mediated diverse modifications affect the ion channel activities and
      spatio-temporally regulate membrane potentials as well as of intracellular Ca(2+)
      concentrations in both excitatory and non-excitatory cells. This article is part
      of a Special Issue entitled: Reciprocal influences between cell cytoskeleton and
      membrane channels, receptors and transporters. Guest Editor: Jean Claude Herve. 

PMID- 24028826
TI  - Long-term outcomes of internet-based self-management support in adults with
      asthma: randomized controlled trial.
AB  - BACKGROUND: Long-term asthma management falls short of the goals set by
      international guidelines. The Internet is proposed as an attractive medium to
      support guided self-management in asthma. Recently, in a multicenter, pragmatic
      randomized controlled parallel trial with a follow-up period of 1 year, patients
      were allocated Internet-based self-management (IBSM) support (Internet group
      [IG]) or usual care (UC) alone. IBSM support was automatically terminated after
      12 months of follow-up. In this study, IBSM support has been demonstrated to
      improve asthma-related quality of life, asthma control, lung function, and the
      number of symptom-free days as compared to UC. IBSM support was based on known
      key components for effective self-management and included weekly asthma control
      monitoring and treatment advice, online and group education, and communication
      (both online and offline) with a respiratory nurse. OBJECTIVE: The objective of
      the study was to assess the long-term effects of providing patients 1 year of
      IBSM support as compared to UC alone. METHODS: Two hundred adults with physician
      diagnosed asthma (3 or more months of inhaled corticosteroids prescribed in the
      past year) from 37 general practices and 1 academic outpatient department who
      previously participated were invited by letter for additional follow-up at 1.5
      years after finishing the study. The Asthma Control Questionnaire (ACQ) and the
      Asthma Quality of Life Questionnaire (AQLQ) were completed by 107 participants
      (60 UC participants and 47 IG participants). A minimal clinical important
      difference in both questionnaires is 0.5 on a 7-point scale. RESULTS: At 30
      months after baseline, a sustained and significant difference in terms of asthma
      related quality of life of 0.29 (95% CI 0.01-0.57) and asthma control of -0.33
      (95% CI -0.61 to -0.05) was found in favor of the IBSM group. No such differences
      were found for inhaled corticosteroid dosage or for lung function, measured as
      forced expiratory volume in 1 second. CONCLUSIONS: Improvements in asthma-related
      quality of life and asthma control were sustained in patients who received IBSM
      support for 1 year, even up to 1.5 years after terminating support. Future
      research should be focused on implementation of IBSM on a wider scale within
      routine asthma care. TRIAL REGISTRATION: International Standard Randomized
      Controlled Trial Number (ISRCTN): 79864465; http://www.controlled
      trials.com/ISRCTN79864465 (Archived by WebCite at
      http://www.webcitation.org/6J4VHhPk4).

PMID- 24028828
TI  - Red scrotum syndrome: idiopathic neurovascular phenomenon or steroid addiction?
AB  - BACKGROUND: Red scrotum syndrome (RSS) is not infrequent but is often
      misdiagnosed or underdiagnosed, and seldom reported. The exact etiopathogeneis is
      still unknown but it almost always follows the prolonged application of topical
      corticosteroids and is characterised by persistent erythema of the scrotum,
      associated with severe itching, hyperalgesia and a burning sensation. OBJECTIVE:
      To evaluate the clinicoepidemiological profile and assess the efficacy of various
      treatment modalities in addition to corticosteroid abstinence in the treatment of
      RSS. METHODS: Twelve patients with RSS, who presented to us during 2010 and 2011,
      were identified, and various aspects of their illness and treatment were studied.
      Patch testing was performed in all patients. A skin biopsy was done in seven
      patients. RESULTS: The average age of the patients was 45.83 years (26-62 years).
      The average duration of illness or the duration of topical steroid use was 27.41
      months (6-56 months). Psychiatric comorbidities were seen in 9 (75%) out of 12
      patients. Histopathology revealed features resembling erythematotelengiectatic
      rosacea in four of the biopsied patients. Patch test results were negative. All
      patients reported improvement of their symptoms within 4 weeks of starting
      doxycycline with amitriptyline or pregabalin; the treatment had to be continued
      for 3-4 months. CONCLUSIONS: RSS appears to be a manifestation of corticosteroid
      misuse rather than a primary disease. We suggest that RSS is a rosacea-like
      dermatosis or steroid-induced rebound vasodilation based on clinical and
      histopathological features. Our patients responded to cessation of steroids and
      doxycycline in combination with amitryptaline or pregabalin.

PMID- 24028829
TI  - Contribution of the ear and the flag leaf to grain filling in durum wheat
      inferred from the carbon isotope signature: genotypic and growing conditions
      effects.
AB  - The ear, together with the flag leaf, is believed to play a major role as a
      source of assimilates during grain filling in C3 cereals. However, the intrusive
      nature of most of the available methodologies prevents reaching conclusive
      results in this regard. This study compares the carbon isotope composition
      (delta(13)C) in its natural abundance in the water-soluble fractions of the flag
      leaf blade and the ear with the delta(13)C of mature kernels to assess the
      relative contribution of both organs to grain filling in durum wheat (Triticum
      turgidum L. var. durum). The relative contribution of the ear was higher in
      landraces compared to modern cultivars, as well as in response to nitrogen
      fertilization and water stress. Such genotypic and environmentally driven
      differences were associated with changes in harvest index (HI), with the relative
      contribution of the ear being negatively associated with HI. In the case of the
      genotypic differences, the lower relative contribution of the ear in modern
      cultivars compared with landraces is probably associated with the appearance in
      the former of a certain amount of source limitation driven by a higher HI. In
      fact, the relative contribution of the ear was far more responsive to changes in
      HI in modern cultivars compared with landraces.

PMID- 24028830
TI  - JPN editorial guidance on the submission of student papers.

PMID- 24028831
TI  - An ethnographic study of HIV/AIDS among Ayoreo sex workers: cultural factors and
      risk perception.
AB  - AIMS AND OBJECTIVES: To describe and understand Ayoreo sex workers' perceptions
      of HIV/AIDS and to identify factors that may affect the prevention of risk
      behaviours. BACKGROUND: According to recent HIV/AIDS incidence reports, being
      female, indigenous and a sex worker means belonging to a maximum-risk group, left
      in the background in terms of strategies for the fight against HIV. Although
      there has been research into intervention models in these populations, it is
      important to detail the perceptions of the problem from the perspective of sex
      workers from the affected ethnic groups. DESIGN: This study used an ethnographic
      methodology that included participant observation and semi-structured interviews.
      METHODS: The research was conducted in two phases. First, participant observation
      was chosen to access and observe the behaviour of Ayoreo sex workers. The second
      phase was a semi-structured interview with sex workers and key informants. The
      interviews, together with the field notes, were transcribed and analysed,
      following inductive strategies to find emerging themes. RESULTS: Here, we present
      the results related to four emerging themes: the cultural acceptance of sex work
      as a useful economic activity; the lack of concern for sexually transmitted
      illnesses and the stigmatisation of people who are HIV seropositive; external
      factors that increase vulnerability such as difficulties in using a condom; and
      conflictive and unbalanced relationships between the Ayoreo people and the health
      system and health professionals. CONCLUSIONS: The health- and sexual reproduction
      related culture, the knowledge and attitudes of sex workers, external factors,
      and relationships with the health system and health professionals continue to
      place Ayoreo sex workers in high-risk conditions in relation to sexually
      transmitted diseases and HIV/AIDS. RELEVANCE TO CLINICAL PRACTICE: Employing
      cultural care as its base, nursing could develop programmes and interventions
      culturally adapted for the prevention of disease and the promotion of health in
      these populations.

PMID- 24028832
TI  - The health and welfare of rural and urban cancer survivors in Missouri.
AB  - INTRODUCTION: An estimated 2.8 million cancer survivors reside in rural areas in
      the United States. We compared the risk behaviors, psychosocial factors, health
      outcomes, quality of life, and follow-up care of rural and urban cancer survivors
      in Missouri. METHODS: We used 2009-2010 Missouri Behavioral Risk Factor
      Surveillance System data to examine various health outcomes, behaviors, and
      psychosocial factors among rural and urban cancer survivors and their respective
      rural and urban counterparts without a cancer history. Cancer survivors also were
      asked about receipt of survivorship care plan components. Sociodemographic
      factors, access to medical care, and chronic conditions were examined as
      potential explanatory factors for differences among the 4 groups. RESULTS: An
      estimated 9.4% of rural and 7.9% of urban Missourians aged 18 years or older
      reported a cancer history. Rural survivors reported the highest rates of poor
      self-reported health, physical distress, and activity limitation; however
      differences between rural and urban survivors were attributable largely to
      sociodemographic differences. Both rural and urban cancer survivors reported more
      fatigue than their respective counterparts without a cancer history. Rural
      survivors also were less likely to meet Centers for Disease Control and
      Prevention recommendations for physical activity than their rural controls. The
      prevalence of smoking among rural survivors was higher than among urban
      survivors. Only 62% of rural survivors versus 78% of urban survivors reported
      receiving advice about cancer follow-up care. CONCLUSION: Rural cancer survivors
      face many health challenges. Interventions to improve quality of life and health
      behaviors should be adapted to meet the needs of rural cancer survivors.

PMID- 24028833
TI  - Factors associated with exposure to antismoking information among adults in
      Vietnam, Global Adult Tobacco Survey, 2010.
AB  - INTRODUCTION: The media play a critical role in tobacco control. Knowledge about
      the exposure of a population to antismoking information can provide information
      for planning communication activities in tobacco control. We examined exposure to
      antismoking information associated with socioeconomic and demographic factors
      among adults (>=15 years) in Vietnam. METHODS: The Global Adult Tobacco Survey
      (GATS) is a nationally representative household survey of noninstitutionalized
      men and women aged 15 years or older and was conducted in Vietnam in 2010 (N =
      9,925). We used GATS data on exposure to sources of antismoking information and
      analyzed associations among socioeconomic and demographic groups. RESULTS: An
      estimated 91.6% of the adult population was exposed to at least 1 source of
      antismoking information, and the mean number of sources of exposure was 3.7.
      Compared with their counterparts, respondents who were older, had higher
      education levels, higher economic status, and higher knowledge levels about the
      health consequences of smoking were more likely to be exposed to any source of
      antismoking information and to more informational sources. The most common source
      of exposure was television (85.9%). Respondents of higher social class
      (education, occupation, wealth) had more exposure through modern media sources
      (television), and respondents of lower social class were exposed to more
      traditional sources such as radio or loudspeakers. CONCLUSION: Exposure to at
      least 1 source of antismoking information is high in Vietnam, and the number and
      type of source varied by sociodemographic group. Use of multiple communication
      channels is recommended to reinforce antismoking messages and to reach different
      groups in the population.

PMID- 24028834
TI  - Office-based physical activity and nutrition intervention: barriers, enablers,
      and preferred strategies for workplace obesity prevention, Perth, Western
      Australia, 2012.
AB  - INTRODUCTION: Workplace health promotion programs to prevent overweight and
      obesity in office-based employees should be evidence-based and comprehensive and
      should consider behavioral, social, organizational, and environmental factors.
      The objective of this study was to identify barriers to and enablers of physical
      activity and nutrition as well as intervention strategies for health promotion in
      office-based workplaces in the Perth, Western Australia, metropolitan area in
      2012. METHODS: We conducted an online survey of 111 employees from 55
      organizations. The online survey investigated demographics, individual and
      workplace characteristics, barriers and enablers, intervention-strategy
      preferences, and physical activity and nutrition behaviors. We used chi(2) and
      Mann-Whitney U statistics to test for differences between age and sex groups for
      barriers and enablers, intervention-strategy preferences, and physical activity
      and nutrition behaviors. Stepwise multiple regression analysis determined factors
      that affect physical activity and nutrition behaviors. RESULTS: We identified
      several factors that affected physical activity and nutrition behaviors,
      including the most common barriers ("too tired" and "access to unhealthy food")
      and enablers ("enjoy physical activity" and "nutrition knowledge"). Intervention
      strategy preferences demonstrated employee support for health promotion in the
      workplace. CONCLUSION: The findings provide useful insights into employees'
      preferences for interventions; they can be used to develop comprehensive programs
      for evidence-based workplace health promotion that consider environmental and
      policy influences as well as the individual.

PMID- 24028835
TI  - A structured management approach to implementation of health promotion
      interventions in Head Start.
AB  - Improving the health and health literacy of low-income families is a national
      public health priority in the United States. The federal Head Start program
      provides a national infrastructure for implementation of health promotion
      interventions for young children and their families. The Health Care Institute
      (HCI) at the Anderson School of Management at the University of California, Los
      Angeles, developed a structured approach to health promotion training for Head
      Start grantees using business management principles. This article describes the
      HCI approach and provides examples of implemented programs and selected outcomes,
      including knowledge and behavior changes among Head Start staff and families.
      This prevention-focused training platform has reached 60,000 Head Start families
      in the United States since its inception in 2001. HCI has demonstrated consistent
      outcomes in diverse settings and cultures, suggesting both scalability and
      sustainability. 

PMID- 24028836
TI  - Recovery of left ventricular and left atrial mechanics in various entities of
      aortic stenosis 12 months after TAVI.
AB  - BACKGROUND: Transcatheter aortic valve implantation (TAVI) has been shown to
      improve prognosis of high-risk patients. Data, however, concerning the impact of
      TAVI on regional and global left atrial (LA) and left ventricular (LV) mechanics
      in varying entities of severe aortic stenosis (AS) are sparse, particularly in
      patients with paradoxical low-flow (PLF) AS or with reduced LV ejection fraction
      (LVEF). This study evaluated the effects of TAVI on LA and LV mechanics in
      varying entities of AS 12 months after implantation. METHODS AND RESULTS: A total
      of 54 consecutive patients with severe AS (24 with a normal LVEF and normal flow,
      16 with PLF, and 14 with a reduced LVEF) were included. Speckle tracking
      echocardiography was performed before and 12 months after TAVI to determine LV
      global and regional longitudinal deformation as well as LA function (reservoir
      function, conduit phase, and active contraction). In all the three entities of
      AS, there was a significant improvement in global and regional LV longitudinal
      function (average global longitudinal strain: -14.1 +/- 3.9% at baseline vs. 
      16.5 +/- 4.0% after TAVI, P < 0.001). Interestingly, the beneficial effects were
      most pronounced in patients with PLF (-14.0 +/- 2.9 vs. -17.0 +/- 4.4%, P <
      0.031). Moreover, the atrial reservoir and conduit function recovered
      significantly after TAVI in all patients. CONCLUSION: In conclusion, regardless
      of the underlying AS entity, TAVI improves global and regional LV and LA
      mechanics within 12 months.

PMID- 24028837
TI  - Imaging-based right-atrial anatomy by computed tomography, magnetic resonance
      imaging, and three-dimensional transoesophageal echocardiography: correlations
      with anatomic specimens.
AB  - Nowadays computed tomography, cardiac magnetic resonance imaging, and
      tridimensional transoesophageal echocardiography provide anatomic images of right
      atrial structures with an impressive richness of anatomical details. It is
      therefore surprising that these techniques are not routinely used as
      complementary tools in teaching anatomy. This review aims to fill this gap
      showing the normal anatomy of right atrium as displayed by these sophisticated
      imaging techniques. A better understanding of right-atrial anatomy is crucial for
      the treatment of primary right-atrium electrical disorders as well as for
      catheter-based interventions for structural heart disease. The success of these
      procedures is, in fact, related to an accurate anatomical pre-procedural
      assessment. In this review, we describe the normal anatomy and variants of those
      right-atrial structures relevant for both ablationists and interventionalists. 

PMID- 24028838
TI  - Clinical relevance of drug efflux pumps in the gut.
AB  - Important export pumps expressed in the apical membrane of enterocytes are P
      glycoprotein (P-gp), breast cancer resistance protein (BCRP) and multidrug
      resistance protein 2 (MRP2). They are believed to be a crucial part of the
      bodies' defense mechanisms against potentially toxic, orally administered
      xenobiotics. In particular P-gp and BCRP also limit the bioavailability of drugs.
      Inhibition of these intestinal export pumps by concomitantly administered drugs
      leads to increased plasma concentrations, whereas induction can reduce absorption
      of the substrate drugs and decrease plasma concentrations. The role of
      polymorphisms in genes encoding for these transporters will also be discussed.
      Taken together this review will focus on the role of intestinal export pumps
      using selected examples from clinical studies in humans. 

PMID- 24028839
TI  - Fas/FasL pathway participates in resolution of mucosal inflammatory response
      early during HSV-2 infection.
AB  - Apoptotic cell death is critical for maintaining integrity of the epithelia as
      well as for removal of the virus infected cells. We assessed the role of Fas/FasL
      dependent pathway in apoptosis of genital epithelium during HSV-2 infection using
      a murine model of HSV-2 infection applied to C57BL6, MRL-Fas(lpr)/J (Fas-/-) and
      C3-Fasl(gld)/J (FasL-/-) mice and an in vitro model of HSV-2 infection in
      monocyte RAW 264.7 and keratinocyte 291.03C cell cultures and peritoneal
      macrophages. In contrast to keratinocyte in vitro cultures, HSV-2 infection of
      the monocytic cell cultures led to early induction of apoptosis. HSV-2 infection
      of peritoneal macrophages isolated from Fas- and FasL-deficient mice showed
      decreased activation of apoptosis, which could be further blocked by caspase-9
      inhibitor. Infection of Fas and FasL-deficient mice increased the percentage of
      apoptotic cells and activation of caspase-9 in the vaginal tissue in comparison
      to C57BL6 wild type strain. Furthermore, Fas and FasL-deficient mice showed
      increased infiltration of neutrophiles in the vaginal mucosal epithelium at 3 and
      7 day of infection in contrast to HSV-2 infected wild-type mice. Our results show
      that while the Fas/FasL pathway during HSV-2 infection of the vaginal epithelium
      plays an important role in controlling early local inflammatory response,
      mitochondrial apoptotic pathway also becomes activated by the inflammatory
      reaction. 

PMID- 24028840
TI  - Carboxypeptidase N-deficient mice present with polymorphic disease phenotypes on
      induction of experimental autoimmune encephalomyelitis.
AB  - Carboxypeptidase N (CPN) is a member of the carboxypeptidase family of enzymes
      that cleave carboxy-terminal lysine and arginine residues from a large number of
      biologically active peptides and proteins. These enzymes are best known for their
      roles in modulating the activity of kinins, complement anaphylatoxins and
      coagulation proteins. Although CPN makes important contributions to acute
      inflammatory events, little is known about its role in autoimmune disease. In
      this study we used CPN(-/-) mice in experimental autoimmune encephalomyelitis
      (EAE), the animal model for multiple sclerosis. Unexpectedly, we observed several
      EAE disease phenotypes in CPN(-/-) mice compared to wild type mice. The majority
      of CPN(-/-) mice died within five to seven days after disease induction, before
      displaying clinical signs of disease. The remaining mice presented with either
      mild EAE or did not develop EAE. In addition, CPN(-/-) mice injected with
      complete or incomplete Freund's adjuvant died within the same time frame and in
      similar numbers as those induced for EAE. Overall, the course of EAE in CPN(-/-)
      mice was significantly delayed and attenuated compared to wild type mice. Spinal
      cord histopathology in CPN(-/-) mice revealed meningeal, but not parenchymal
      leukocyte infiltration, and minimal demyelination. Our results indicate that CPN
      plays an important role in EAE development and progression and suggests that
      multiple CPN ligands contribute to the disease phenotypes we observed. 

PMID- 24028841
TI  - A case-control study to assess the urinary pneumococcal antigen test in childhood
      pneumonia.

PMID- 24028842
TI  - The effect of a medical clown on pain during intravenous access in the pediatric
      emergency department: a randomized prospective pilot study.
AB  - BACKGROUND: We report the effect of the presence of a medical clown during
      insertion of an intravenous catheter during their emergency department visit.
      METHODS: Prospectively randomized to either the presence or absence of a male
      medical clown during the procedure. Pain was assessed using the Faces Pain Scale
      Revised in children 4 to 7 years old, and visual analog scales in children 8
      years and older. Parental situational anxiety was recorded using the State-Trait
      Anxiety Inventory after the procedure. RESULTS: The presence of a medical clown
      during a painful procedure in the pediatric emergency department tended to
      improve pain scores in children younger than 7 years. Parental situational
      anxiety was significantly reduced in parents of children older than 8 years (P =
      .02). CONCLUSION: Therapeutic clowns are useful for diminishing pain and anxiety
      during painful procedures being performed on children in the emergency
      department.

PMID- 24028843
TI  - Fluid intake history and counseling in pediatric outpatients.
AB  - OBJECTIVE: To determine if (a) during well visits physicians are discussing 6
      common fluids and (b) if there is any association between fluid discussion and
      patient age, gender, or body mass index. METHODS: We performed a retrospective
      chart review of 500 pediatric well visits. We analyzed the relationships between
      history and/or counseling on fluid intake and patient age, gender, and body mass
      index percentile using logistic regression and likelihood ratio chi-square
      testing. RESULTS: Caffeinated beverages were discussed more with overweight/obese
      patients compared with normal weight patients. Juice, caffeinated, and carbonated
      beverages were all discussed more with obese patients compared with overweight
      patients. Water, carbonated, and caffeinated beverages were discussed more with
      older patients, and milk with younger patients. Juice was discussed more with
      female patients. CONCLUSION: Pediatricians discuss high-calorie fluids more
      frequently with obese children but not more frequently with overweight children,
      which may be an optimal time to prevent obesity.

PMID- 24028844
TI  - Selective acquisition and retention of genomic sequences by Pack-Mutator-like
      elements based on guanine-cytosine content and the breadth of expression.
AB  - The process of gene duplication followed by sequence and functional divergence is
      important for the generation of new genes. Pack-MULEs, nonautonomous Mutator-like
      elements (MULEs) that carry genic sequence(s), are potentially involved in
      generating new open reading frames and regulating parental gene expression. These
      elements are identified in many plant genomes and are most abundant in rice
      (Oryza sativa). Despite the abundance of Pack-MULEs, the mechanism by which
      parental genes are captured by Pack-MULEs remains largely unknown. In this study,
      we identified all MULEs in rice and examined factors likely important for
      sequence acquisition. Terminal inverted repeat MULEs are the predominant MULE
      type and account for the majority of the Pack-MULEs. In addition to genic
      sequences, rice MULEs capture guanine-cytosine (GC)-rich intergenic sequences,
      albeit at a much lower frequency. MULEs carrying nontransposon sequences have
      longer terminal inverted repeats and higher GC content in terminal and
      subterminal regions. An overrepresentation of genes with known functions and
      genes with orthologs among parental genes of Pack-MULEs is observed in rice,
      maize (Zea mays), and Arabidopsis (Arabidopsis thaliana), suggesting preferential
      acquisition for bona fide genes by these elements. Pack-MULEs selectively
      acquire/retain parental sequences through a combined effect of GC content and
      breadth of expression, with GC content playing a stronger role. Increased GC
      content and number of tissues with detectable expression result in higher chances
      of a gene being acquired by Pack-MULEs. Such selective acquisition/retention
      provides these elements greater chances of carrying functional sequences that may
      provide new genetic resources for the evolution of new genes or the modification
      of existing genes. 

PMID- 24028845
TI  - Vacuolar transport of abscisic acid glucosyl ester is mediated by ATP-binding
      cassette and proton-antiport mechanisms in Arabidopsis.
AB  - Abscisic acid (ABA) is a key plant hormone involved in diverse physiological and
      developmental processes, including abiotic stress responses and the regulation of
      stomatal aperture and seed germination. Abscisic acid glucosyl ester (ABA-GE) is
      a hydrolyzable ABA conjugate that accumulates in the vacuole and presumably also
      in the endoplasmic reticulum. Deconjugation of ABA-GE by the endoplasmic
      reticulum and vacuolar beta-glucosidases allows the rapid formation of free ABA
      in response to abiotic stress conditions such as dehydration and salt stress. ABA
      GE further contributes to the maintenance of ABA homeostasis, as it is the major
      ABA catabolite exported from the cytosol. In this work, we identified that the
      import of ABA-GE into vacuoles isolated from Arabidopsis (Arabidopsis thaliana)
      mesophyll cells is mediated by two distinct membrane transport mechanisms: proton
      gradient-driven and ATP-binding cassette (ABC) transporters. Both systems have
      similar Km values of approximately 1 mm. According to our estimations, this low
      affinity appears nevertheless to be sufficient for the continuous vacuolar
      sequestration of ABA-GE produced in the cytosol. We further demonstrate that two
      tested multispecific vacuolar ABCC-type ABC transporters from Arabidopsis exhibit
      ABA-GE transport activity when expressed in yeast (Saccharomyces cerevisiae),
      which also supports the involvement of ABC transporters in ABA-GE uptake. Our
      findings suggest that the vacuolar ABA-GE uptake is not mediated by specific, but
      rather by several, possibly multispecific, transporters that are involved in the
      general vacuolar sequestration of conjugated metabolites. 

PMID- 24028847
TI  - Tradition.

PMID- 24028846
TI  - Overexpression of the vacuolar sugar carrier AtSWEET16 modifies germination,
      growth, and stress tolerance in Arabidopsis.
AB  - Here, we report that SUGARS WILL EVENTUALLY BE EXPORTED TRANSPORTER (SWEET16)
      from Arabidopsis (Arabidopsis thaliana) is a vacuole-located carrier,
      transporting glucose (Glc), fructose (Fru), and sucrose (Suc) after heterologous
      expression in Xenopus laevis oocytes. The SWEET16 gene, similar to the homologs
      gene SWEET17, is mainly expressed in vascular parenchyma cells. Application of
      Glc, Fru, or Suc, as well as cold, osmotic stress, or low nitrogen, provoke the
      down-regulation of SWEET16 messenger RNA accumulation. SWEET16 overexpressors
      (35SPro:SWEET16) showed a number of peculiarities related to differences in sugar
      accumulation, such as less Glc, Fru, and Suc at the end of the night. Under cold
      stress, 35SPro:SWEET16 plants are unable to accumulate Fru, while under nitrogen
      starvation, both Glc and Fru, but not Suc, were less abundant. These changes of
      individual sugars indicate that the consequences of an increased SWEET16 activity
      are dependent upon the type of external stimulus. Remarkably, 35SPro:SWEET16
      lines showed improved germination and increased freezing tolerance. The latter
      observation, in combination with the modified sugar levels, points to a superior
      function of Glc and Suc for frost tolerance. 35SPro:SWEET16 plants exhibited
      increased growth efficiency when cultivated on soil and showed improved nitrogen
      use efficiency when nitrate was sufficiently available, while under conditions of
      limiting nitrogen, wild-type biomasses were higher than those of 35SPro:SWEET16
      plants. Our results identify SWEET16 as a vacuolar sugar facilitator, demonstrate
      the substantial impact of SWEET16 overexpression on various critical plant
      traits, and imply that SWEET16 activity must be tightly regulated to allow
      optimal Arabidopsis development under nonfavorable conditions. 

PMID- 24028848
TI  - Avoidance of affective pain stimuli predicts chronicity in patients with acute
      low back pain.
AB  - This prospective study of acute and sub-acute low back pain (LBP) patients was
      conducted to assess whether attentional biases predicted chronic pain status 3
      and 6 months later. The attentional biases of 100 LBP patients were assessed
      within 3 months of developing pain and 6 months later. Participants also
      completed measures associated with outcome at 3 assessment points: baseline, 3
      and 6 months later. Current pain status was assessed at follow-ups. Patients were
      classified as those that met standard criteria for chronic pain or those who did
      not (i.e., the comparison group). At baseline, participants demonstrated a bias
      toward sensory pain words. However, biases toward sensory pain words did not
      differentiate those who subsequently developed chronic pain and those who did not
      at either follow-up. The same bias was observed 6 months later, but again it
      failed to distinguish between the chronic pain and comparison groups. However,
      subjects who developed chronic pain at both 3 (n=22) and 6 (n=21) months
      demonstrated biases away from affective pain words at baseline but not 6 months
      later, in comparison to other participants. These results remained significant in
      multivariate analyses. These findings are consistent with patterns observed in
      the previous research, and suggest that avoidance of emotionally laden pain
      related stimuli (i.e., affective pain words) is associated with negative outcomes
      for LBP patients in the acute and sub-acute phase. This research suggests that
      attentional biases in relation to pain-related stimuli are important for the
      development of chronic pain, but are more complex than initially thought.

PMID- 24028849
TI  - Beta-casein and its complexes with chitosan as nanovehicles for delivery of a
      platinum anticancer drug.
AB  - The clinical application of platinum-based anticancer drugs is greatly limited by
      severe toxicity. Drug-delivery systems are much sought after to improve the
      efficacy and applicability of these drugs. Here, we describe a new drug-delivery
      system comprising a novel platinum complex (bipyridine morpholine dithiocarbamate
      Pt(II) nitrate) within nanoparticles composed of beta-casein (beta-CN) and
      chitosan (CS). The influence of pH on the formation of a colloidally-stable
      nanocarrier system composed of Pt complex-loaded beta-CN and chitosan
      nanoparticles was investigated using UV-vis spectrometry, dynamic light
      scattering (DLS) and scanning electron microscopy (SEM). The particles of Pt
      complex-loaded beta-casein-chitosan formed were stable and soluble in the pH
      range 5.7-6.2. Hence, the optimal pH for complex formation is between the pI of
      casein (5.3) and the pKa of chitosan (6.5). DLS data showed that, at both pH
      values of 5.7 and 6.2, the particles formed had sizes between 200 and 300nm.
      However, the optimum pH for particle formation was pH 5.7. At this pH, the zeta
      potential values of nanoparticles were positive and the particles were stable.
      SEM analysis confirmed the formation of nanoparticles with good colloidal
      stability and an average particle size of 200nm. The cytotoxicity of both free
      and encapsulated Pt complex was evaluated on colorectal carcinoma HCT116 cells.
      The results obtained indicated that both the cytotoxicity and cellular uptake of
      platinum were enhanced by its entrapment in beta-CN-CS nanovehicles. These
      findings suggest that this novel drug-delivery system enables drugs to be
      thermodynamically stable in aqueous solutions and is potentially useful for
      targeted oral-delivery applications. 

PMID- 24028850
TI  - Binding study of novel anti-diabetic pyrimidine fused heterocycles to beta
      lactoglobulin as a carrier protein.
AB  - Bovine milk beta-lactoglobulin (beta-LG) demonstrates significant resistance
      against both gastric- and simulated duodenal digestions. Therefore, it seems a
      realistic protein candidate for safe delivery and protection of particularly pH
      sensitive drugs in stomach. Recently, pyrimidine fused heterocycles (PFHs)
      revealed inhibitory properties against alpha-glucosidase (alpha-Gls) which is an
      important target enzyme for those drugs playing significant role in treatment of
      type-II diabetes and HIV/AIDS infection. The delivery of these compounds to small
      intestine where the enzyme plays its biological function is of great importance.
      Therefore, in this work the interaction of PFH compounds with beta-LG, as a
      carrier protein has been investigated. Fluorescence, circular dichroism (CD) and
      UV-vis spectroscopic studies were used to examine the binding parameters and
      binding modes of the interaction. Moreover, the effects of PFH complexation on
      the secondary structures of beta-LG were studied. All of these compounds
      significantly quenched the fluorescence intensity of beta-LG due to a ground
      state complex formation. The binding and thermodynamic parameters were
      calculated. While hydrophobic interactions were proved to play significant role
      in the interaction of L1, L2 and L3, hydrogen bonding was shown to be important
      in the complexation of L4. The secondary structures of beta-LG were preserved
      upon interaction of these synthetic compounds. Based on the achieved results,
      these potentially therapeutic agents can significantly bind to beta-LG.
      Consequently, this protein might be useful for delivery of PFH compounds to small
      intestine where representing their potential ability to inhibit alpha-Gls and to
      reduce the postprandial hyperglycemia in diabetic patients. 

PMID- 24028851
TI  - Synthesis and characterization of jacalin-gold nanoparticles conjugates as
      specific markers for cancer cells.
AB  - New nanobiocomposites that combine nanoparticles and biomolecules have been shown
      very relevant for medical applications. Recently, cancer diagnostics and
      treatment have benefited from the development of nanobiocomposites, in which
      metallic or magnetic nanoparticles are conjugated with specific biomolecules for
      selective cell uptake. Despite recent advances in this area, the biomedical
      applications of these materials are still limited by the low efficiency of
      functionalization, low stability, among other factors. In this study, we report
      the synthesis of jacalin-conjugated gold nanoparticles, a nanoconjugate with
      potential application in medical areas, especially for cancer diagnosis. Jacalin
      is a lectin protein and it was employed due to its ability to recognize the
      Galbeta1-3GalNAc disaccharide, which is highly expressed in tumor cells. Gold
      nanoparticles (AuNPs) were synthesized in the presence of generation 4
      polyamidoamine dendrimer (PAMAM G4) and conjugated with fluorescein
      isothiocyanate (FITC)-labeled jacalin. The AuNPs/jacalin nanoconjugates were
      characterized by transmission electron microscopy (TEM), dynamic light scattering
      (DLS) and vibrational spectroscopy (FTIR). We also performed an investigation
      using isothermal titration calorimetry (ITC) and fluorescence quenching
      measurements to understand the interactions occurring between the AuNPs and
      jacalin, which revealed that the nanoconjugate formation is driven by an entropic
      process with good affinity. Furthermore, in vitro tests revealed that the
      AuNPs/jacalin-FITC nanoconjugates exhibited higher affinity for leukemic K562
      cells than for healthy mononuclear blood cells, which could be useful for
      biomedical applications, including cancer cells imaging. 

PMID- 24028852
TI  - Mechanism of action of the levonorgestrel-releasing intrauterine system in the
      treatment of heavy menstrual bleeding.
AB  - OBJECTIVE: To assess the efficacy and adverse effects, and reveal the effective
      pathway of the levonorgestrel-releasing intrauterine system (LNG-IUS) in the
      treatment of heavy menstrual bleeding. METHODS: In a prospective single-center
      study in Istanbul, Turkey, the LNG-IUS was inserted in 60 patients diagnosed with
      heavy menstrual bleeding between January 2008 and June 2010. Menstrual bleeding
      pattern, coagulation parameters, uterine arterial blood flow, endometrial
      thickness, and uterine and ovarian volumes were assessed pre-insertion, and at 6
      and 12months. RESULTS: Forty-nine women completed the study. When compared with
      pre-insertion values, the LNG-IUS led to improvements in hemoglobin and marked
      decreases in visual bleeding scores, endometrial thickness, and fibrinogen levels
      (P<0.001); platelet count, international normalized ratio, prothrombin time,
      activated partial thromboplastin time, and uterine volume also decreased
      (P<0.05). No significant change in ovarian volumes, or uterine artery resistive
      and pulsatility indices was observed at 6 or 12months compared with pre-insertion
      values. CONCLUSION: The decline in menstrual blood loss among LNG-IUS users was
      associated with local progestogenic effects and aggravation of intrinsic and
      extrinsic coagulation pathways. Although the LNG-IUS is a highly effective method
      for treating heavy menstrual bleeding, care must be taken when a patient has
      thromboembolic risk factors.

PMID- 24028853
TI  - Current obstetric practices: Are we on the right track?

PMID- 24028854
TI  - The effect of dissolved organic matter (DOM) on sodium transport and nitrogenous
      waste excretion of the freshwater cladoceran (Daphnia magna) at circumneutral and
      low pH.
AB  - Dissolved organic matter (DOM), a heterogeneous substance found in all natural
      waters, has many documented abiotic roles, but recently, several possible direct
      influences of DOM on organism physiology have been reported. However, most
      studies have been carried out with a limited number of natural DOM isolates or
      were restricted to the use of commercial or artificial humic substances. We
      therefore employed three previously characterized, chemically-distinct natural
      DOMs, as well as a commercially available humic acid (Aldrich, AHA), at
      circumneutral (7-8) and acidic pH (~5), to examine DOM effects on whole-body
      Na(+) concentration, unidirectional influx and efflux rates of Na(+), and ammonia
      and urea excretion rates in Daphnia magna. Whole-body Na(+) concentration, Na(+)
      influx, and Na(+) efflux rates were all unaffected regardless of pH, suggesting
      no influence of the various natural DOMs on active uptake and passive diffusion
      of Na(+) in this organism. Ammonia and urea excretion rates were both increased
      by low pH. Ammonia excretion rates were reduced at circumneutral pH by the most
      highly colored, allochthonous DOM, and at low pH by all three natural DOMs, as
      well as by the commercial AHA. Urea excretion rates were not influenced by the
      presence of the various DOMs in circumneutral solutions, but were attenuated by
      the presence of two allochthonous DOM sources (isolated from Bannister Lake and
      Luther Marsh) at acidic pH. The observed reductions may be attributed partially
      to the higher buffering capacities of natural DOM sources, as well as their
      ability to interact with biological membranes as estimated by a new measure
      calculated from their acid-base titration characteristics, the Proton Binding
      Index (PBI). 

PMID- 24028855
TI  - Effect of pharmaceuticals exposure on acetylcholinesterase (AchE) activity and on
      the expression of AchE gene in the monogonont rotifer, Brachionus koreanus.
AB  - Pharmaceuticals are widely used in human and veterinary medicine. However, they
      are emerging as a significant contaminant in aquatic environments through
      wastewater. Due to the persistent and accumulated properties of pharmaceuticals
      via the food web, their potential harmful effects on aquatic animals are a great
      concern. In this study, we investigated the effects of six pharmaceuticals:
      acetaminophen, ATP; atenolol, ATN; carbamazepine, CBZ; oxytetracycline, OTC;
      sulfamethoxazole, SMX; and trimethoprim, TMP on acetylcholinesterase (AChE; EC
      3.1.1.7) activity and its transcript expression with chlorpyrifos (as a positive
      control) in the monogonont rotifer, Brachionus koreanus. ATP, CBZ, and TMP
      exposure also remarkably inhibited Bk-AChE activity at 100 MUg/L (24 h) and 1000
      MUg/L (12 h and 24 h). ATP, CBZ, and TMP exposure showed a significant decrease
      in the Bk-AChE mRNA level in a concentration-dependent manner. However, in the
      case of OTC and SMX, a slight decrease in Bk-AChE mRNA expression was found but
      only at the highest concentration. The time-course experiments showed that ATP
      positively induced Bk-AChE mRNA 12 h after exposure at both 100 and 1000 MUg/L,
      while the Bk-AChE mRNA expression was significantly downregulated over 6 to 24 h
      after exposure to 1000 MUg/L of CBZ, OTC, SMX, and TMP. Our findings suggest that
      Bk-AChE would be a useful biomarker for risk assessment of pharmaceutical
      compounds as an early signal of their toxicity in aquatic environments.
      Particularly, ATP, CBZ, and TMP may have a toxic cholinergic effect on rotifer B.
      koreanus by inhibiting AChE activity.

PMID- 24028856
TI  - Intrapancreatic ganglia neurons receive projection fibers from melanocortin-4
      receptor-expressing neurons in the dorsal motor nucleus of the vagus nerve of the
      mouse.
AB  - Melanocortin-4 receptor (MC4R)-expressing neurons are widely distributed in the
      central nervous system and play a crucial role in a variety of physiological
      functions including energy and glucose/insulin homeostasis. However, their neural
      pathways remain to be elucidated. In the present study, we examined a possible
      pathway from MC4R-expressing neurons in the dorsal motor nucleus of the vagus
      nerve (DMV) to the intrapancreatic ganglia using transgenic mice that express
      green fluorescent protein (GFP) under the control of the MC4R-promoter. Using
      immunofluorescence labeling, we demonstrated that GFP-immunoreactive (ir) nerve
      fibers were distributed in the intrapancreatic ganglia closely associated with
      the islets as well as among the acini. These GFP-ir fibers with bouton-like
      varicosities were frequently observed to surround ganglion cells immunoreactive
      for vasoactive intestinal polypeptide, a marker for postganglionic
      parasympathetic neurons. Using the pre-embedding immunoperoxidase method, we
      clearly showed that GFP-ir terminals formed synapses predominantly with dendrites
      and additionally with somata of the ganglion cells. Moreover, bilateral
      subdiaphragmatic vagotomy caused a marked loss of GFP immunoreactivity in the
      pancreas. Using a combination of retrograde tracing and immunohistochemistry, we
      finally demonstrated that nearly half of the pancreas-projecting DMV neurons were
      immunoreactive for GFP. These results suggest that MC4R-expressing DMV neurons
      may participate in the regulation of glucose/insulin homeostasis through their
      projections to the intrapancreatic ganglia. 

PMID- 24028857
TI  - Association of indoor dampness and molds with rhinitis risk: a systematic review
      and meta-analysis.
AB  - BACKGROUND: A substantial proportion of the world's population is exposed to
      indoor dampness-related exposures. Since the 1990s, studies have assessed the
      relation between indoor dampness and mold and rhinitis, but the evidence has been
      inconclusive. No previous meta-analysis has been reported on this topic.
      OBJECTIVE: We conducted a systematic review and meta-analysis of studies on the
      relations between indoor dampness and mold and the risk of different types of
      rhinitis and investigated whether these relations differ according to the type of
      exposure. METHODS: A systematic search of the Ovid MEDLINE and EMBASE databases
      was conducted (1950 through August 2012), and reference lists of relevant
      articles were reviewed. Cross-sectional, case-control, and cohort studies in
      children or adults were selected according to a priori criteria and evaluated by
      3 authors independently. RESULTS: Thirty-one studies on rhinitis, allergic
      rhinitis (AR), or rhinoconjunctivitis were included. In meta-analyses the largest
      risk was observed in relation to mold odor (rhinitis: 2.18 [95% CI, 1.76-2.71];
      AR: 1.87 [95% CI, 0.95-3.68]). The risk related to visible mold was also
      consistently increased (rhinitis: 1.82 [95% CI, 1.56-2.12]; AR: 1.51 [95% CI,
      1.39-1.64]; rhinoconjunctivitis: 1.66 [95% CI, 1.27-2.18]). In addition, exposure
      to dampness was related to increased risk of all types of rhinitis. CONCLUSION:
      This meta-analysis provides new evidence that dampness and molds at home are
      determinants of rhinitis and its subcategories. The associations were strongest
      with mold odor, suggesting the importance of microbial causal agents. Our results
      provide evidence that justifies prevention and remediation of indoor dampness and
      mold problems, and such actions are likely to reduce rhinitis.

PMID- 24028858
TI  - Reduced breast cancer incidence in women treated with subcutaneous testosterone,
      or testosterone with anastrozole: a prospective, observational study.
AB  - OBJECTIVES: There is evidence that androgens are breast protective and that
      testosterone therapy treats many symptoms of hormone deficiency in both pre and
      postmenopausal patients. However, unlike estrogen and progestins, there is a
      paucity of data regarding the incidence of breast cancer in women treated with
      testosterone therapy. This study was designed to investigate the incidence of
      breast cancer in women treated with subcutaneous testosterone therapy in the
      absence of systemic estrogen therapy. STUDY DESIGN: This is a 5-year interim
      analysis of a 10-year, prospective, observational, IRB approved study
      investigating the incidence of breast cancer in women presenting with symptoms of
      hormone deficiency treated with subcutaneous testosterone (T) implants or, T
      combined with the aromatase inhibitor anastrozole (A), i.e., T+A implants. Breast
      cancer incidence was compared with that of historical controls reported in the
      literature, age specific Surveillance Epidemiology and End Results (SEER)
      incidence rates, and a representative, similar age group of our patients used as
      a 'control' group. The effect of adherence to T therapy was also evaluated.
      RESULTS: Since March 2008, 1268 pre and post menopausal women have been enrolled
      in the study and eligible for analysis. As of March 2013, there have been 8 cases
      of invasive breast cancer diagnosed in 5642 person-years of follow up for an
      incidence of 142 cases per 100000 person-years, substantially less than the age
      specific SEER incidence rates (293/100000), placebo arm of Women's Health
      Initiative Study (300/100000), never users of hormone therapy from the Million
      Women Study (325/100000) and our control group (390/100000). Unlike adherence to
      estrogen therapy, adherence to T therapy further decreased the incidence of
      breast cancer (73/100000). CONCLUSION: T and/or T+A, delivered subcutaneously as
      a pellet implant, reduced the incidence of breast cancer in pre and
      postmenopausal women. Evidence supports that breast cancer is preventable by
      maintaining a T to estrogen ratio in favor of T and, in particular, by the use of
      continuous T or, when indicated, T+A. This hormone therapy should be further
      investigated for the prevention and treatment of breast cancer.

PMID- 24028859
TI  - Association of gonial angle with morphology and bone mineral content of the body
      of the adult human mandible with complete permanent dentition.
AB  - We investigated the differences between 2 gonial angle (GA) size groups with
      respect to the morphometry and quantitative bone mineral content (QBMC) of
      mandibles with all teeth erupted and normal occlusion. We used 19 dried mandibles
      that were obtained from an Indian population and stored in our department. These
      mandibles were at Hellman's developmental dental stage VA and were divided into
      low gonial angle (LGA) (GA <= 120 degrees ; 8 specimens; 16 sides) and high
      gonial angle (HGA) (GA >= 125 degrees ; 11 specimens; 22 sides) groups. After
      lateral radiography of the mandibles using a titanium step wedge, linear
      measurements and the QBMC were determined, on hard copies and digital images,
      respectively. The age and sex of the cadavers to which the specimens belonged
      were unknown. The mandibular cortical width (MCW) and the antegonial notch depth
      of the LGA group were significantly larger than those of the HGA group. No
      significant difference was found in the distribution of the 3 categories of
      mandibular cortical index (MCI) or in cortical and trabecular bone mineral
      contents (CBMC and TBMC). The GA size was negatively and moderately associated
      with the MCW and the mandibular cortical width on the point AG (MCWAG), but was
      not significantly associated with either variable for CBMC and TBMC. These
      results suggested that the GA size of these stage-VA mandibles influenced changes
      in the width of inferior cortex and morphology of antegonial notch. The GA size
      did not influence QBMC under the mental foramen of the mandible and had negative
      associations with the MCW and MCWAG.

PMID- 24028860
TI  - Functional differentiation of the human lumbar perivertebral musculature
      revisited by means of muscle fibre type composition.
AB  - Human back muscles have been classified as local stabilizers, global stabilizers
      and global mobilizers. This concept is supported by the distribution of slow and
      fast muscle fibres in quadrupedal mammals, but has not been evaluated for humans
      because detailed information on the fibre type composition of their perivertebral
      musculature is rare. Moreover, such information is derived from spot samples,
      which are assumed to be representative for the respective muscle. In accordance
      with the proposed classification, numerous studies in animals indicate great
      differences in the fibre distribution within and among the muscles due to fibre
      type regionalization. The aims of this study were to (1) qualitatively explore
      the applicability of the proposed functional classification for human back
      muscles by studying their fibre type composition and (2) evaluate the
      representativeness of spot sampling techniques. For this, the fibre type
      distribution of the whole lumbar perivertebral musculature of two male cadavers
      was investigated three-dimensionally using immunohistochemistry. Despite great
      local variations (e.g., among fascicles), all muscles were composed of about 50%
      slow and 50% fast fibres. Thus, contradicting the concepts of lumbar muscle
      function, no functional differentiation of the muscles was observed in our study
      of the muscle contractile properties. The great similarity in fibre composition
      among the muscles equips each muscle equally well for a broad range of tasks and
      therefore has the potential to allow for great functional versatility of the
      human back musculature. Spot samples do not prove to be representative for the
      whole muscle. The great intraspecific variability observed previously in single
      spot samples is potentially misleading.

PMID- 24028861
TI  - Photo-conversion of CO2 using titanium dioxide: enhancements by plasmonic and co
      catalytic nanoparticles.
AB  - Converting carbon dioxide (CO2) to hydrocarbons that can be used as fuels is
      beneficial from both environmental and economic points of view. In this study,
      nanoparticles are designed to enhance the photoreduction of CO2 on a titanium
      dioxide (TiO2) catalyst. An increase in catalytic activity is reported when
      silver (Ag), platinum (Pt) or bimetallic Ag-Pt and core-shell Ag@silica (SiO2)
      nanoparticles are used with the TiO2 semiconductor catalyst. Nanoparticles with
      different elemental composition or geometrical structure facilitate successive
      photo-excitation steps-generation, transport, storage and interfacial transfer of
      electrons and holes. Results show that while the addition of either type of
      nanoparticles augments product formation rates, bimetallic co-catalysts improve
      product selectivity. When both bimetallic co-catalysts and Ag@SiO2 nanoparticles
      are used in combination, product yields are enhanced more than seven fold in
      comparison to native TiO2 and high selectivity for methane (CH4) is observed.
      When the bimetallic Ag-Pt co-catalysts are tuned, a selectivity of CH4 of
      approximately 80%, as compared to 20% with only TiO2, can be achieved. 

PMID- 24028862
TI  - Divergence of repetitive DNA sequences in the heterochromatin of medaka fishes:
      Molecular cytogenetic characterization of constitutive heterochromatin in two
      medaka species: Oryzias hubbsi and O. celebensis (Adrianichthyidae,
      Beloniformes).
AB  - The large biarmed chromosomes of Oryzias celebensis [2n = 36, fundamental arm
      number (FN) = 48] are considered to have resulted from fusions of acrocentric
      chromosomes in the ancestral karyotype of Oryzias, which is retained in O. hubbsi
      (2n = 48, FN = 48). To understand the molecular evolution of heterochromatin
      associated with karyotype reorganization in medaka fishes, we cloned 3 and 6
      novel families of heterochromatin-related repetitive DNA sequences from O. hubbsi
      and O. celebensis, respectively, and characterized them using molecular
      cytogenetics. Two AT-rich repetitive sequences isolated from the genomic DNA of
      O. hubbsi, a 164-bp satellite DNA (OHU-RsaI-Scen) and a 177-bp telomere-specific
      repeat (OHU-RsaI-Stelo), were shown to be major components of the constitutive
      heterochromatin of centromeres and telomeres, respectively. A GC-rich 326-bp
      sequence, named OHU-AluI-M1, was colocalized with the 18S-28S ribosomal RNA gene
      cluster to a single autosomal pair of chromosomes and the W chromosome. In O.
      celebensis, 2 major satellite DNA sequences (the AT-rich 157-bp OCE-AluI-Scen
      sequence and the 186-bp OCE-HinfI-Scen sequence) were identified in the
      centromeric regions of almost all chromosomes. The 197-bp OCE-HinfI-S6 sequence
      was located in the centromeric and distal and/or interstitial heterochromatin of
      almost all chromosomes, and the 191-bp OCE-HinfI-S8 sequence was located in 6
      pairs of chromosomes. Constitutive heterochromatin on the short arm of large
      submetacentric chromosome 5 was composed of at least 3 different repetitive
      sequences: the 171-bp OCE-AluI-S18 sequence, the 197-bp OCE-HinfI-S6 sequence and
      the 172-bp OCE-HinfI-S11 sequence. All families of repeated sequences showed no
      nucleotide sequence similarity with each other and high species-specificity among
      7 different species. These results suggest that the heterochromatin of O. hubbsi
      and O. celebensis consists of various types of repetitive sequence and that the
      sequences evolved independently and were then amplified site-specifically in each
      lineage after karyotype reorganization occurred in the ancestral karyotype.

PMID- 24028864
TI  - One confirmed and one suspected case of pharyngeal gonorrhoea treatment failure
      following 500mg ceftriaxone in Sydney, Australia.
AB  - Emerging antimicrobial resistance within Neisseria gonorrhoeae (NG) is a
      significant global public health threat. Detection and investigation of treatment
      failures is a crucial component of the World Health Organisation's response to
      this challenge. We report the cases of two homosexual men, both treated for
      pharyngeal NG with 500mg intramuscular ceftriaxone, in whom a test of cure 1 week
      after treatment showed persisting infection. Both men denied further sexual
      activity. In the first case, treatment failure was confirmed, since the isolates
      before and after treatment were identical by auxotype, antibiogram, multilocus
      sequence type (MLST) and multi-antigen sequence type (NG-MAST). In the second
      case, the MLSTs before and after treatment were identical, but NG-MAST results
      were similar but not indistinguishable. These cases underline the importance of
      test-of-cure and molecular investigations in identifying treatment failure, but
      also highlight the complexity of distinguishing treatment failure from
      reinfection when relying on highly variable molecular targets that may be subject
      to drug pressure. 

PMID- 24028863
TI  - Anti-plasmodial activity of aroylhydrazone and thiosemicarbazone iron chelators:
      effect on erythrocyte membrane integrity, parasite development and the
      intracellular labile iron pool.
AB  - Iron chelators inhibit the growth of the malaria parasite, Plasmodium falciparum,
      in culture and in animal and human studies. We previously reported the anti
      plasmodial activity of the chelators, 2-hydroxy-1-naphthylaldehyde isonicotinoyl
      hydrazone (311), 2-hydroxy-1-naphthylaldehyde 4-methyl-3-thiosemicarbazone
      (N4mT), and 2-hydroxy-1-naphthylaldehyde 4-phenyl-3-thiosemicarbazone (N4pT). In
      fact, these ligands showed greater growth inhibition of chloroquine-sensitive
      (3D7) and chloroquine-resistant (7G8) strains of P. falciparum in culture
      compared to desferrioxamine (DFO). The present study examined the effects of 311,
      N4mT and N4pT on erythrocyte membrane integrity and asexual parasite development.
      While the characteristic biconcave disk shape of the erythrocytes was unaffected,
      the chelators caused very slight hemolysis at IC50 values that inhibited parasite
      growth. The chelators 311, N4mT and N4pT affected all stages of the intra
      erythrocytic development cycle (IDC) of P. falciparum in culture. However, while
      these ligands primarily affected the ring-stage, DFO inhibited primarily
      trophozoite and schizont-stages. Ring, trophozoite and schizont-stages of the IDC
      were inhibited by significantly lower concentrations of 311, N4mT, and N4pT
      (IC50=4.45+/-1.70, 10.30+/-4.40, and 3.64+/-2.00MUM, respectively) than DFO
      (IC50=23.43+/-3.40MUM). Complexation of 311, N4mT and N4pT with iron reduced
      their anti-plasmodial activity. Estimation of the intracellular labile iron pool
      (LIP) in erythrocytes showed that the chelation efficacy of 311, N4mT and N4pT
      corresponded to their anti-plasmodial activities, suggesting that the LIP may be
      a potential source of non-heme iron for parasite metabolism within the
      erythrocyte. This study has implications for malaria chemotherapy that
      specifically disrupts parasite iron utilization. 

PMID- 24028865
TI  - Impact of the cellular prion protein on amyloid-beta and 3PO-tau processing.
AB  - Previous studies indicate an important role for the cellular prion protein
      (PrP(C)) in the development of Alzheimer's disease (AD) pathology. In the present
      study, we analyzed the involvement of PrP(C) in different pathological mechanisms
      underlying AD: the processing of the amyloid-beta protein precursor (AbetaPP) and
      its interaction with AbetaPP, tau, and different phosphorylated forms of the tau
      protein (p-tau). The effect of PrP(C) on tau expression was investigated in
      various cellular compartments using a HEK293 cell model expressing a tau mutant
      (3PO-tau) or wild type (WT)-tau. We could show that PrP(C) reduces AbetaPP
      cleavage, leading to decreased levels of Abeta40 and sAbetaPP without changing
      the protein expression of AbetaPP, beta-secretase, or gamma-secretase. Tau and
      its phosphorylated forms were identified as interactions partners for PrP(C),
      raising the question as to whether PrP(C) might also be involved in tau
      pathology. Overexpression of PrP(C) in PRNP and 3PO-tau transfected cells
      resulted in a reduction of 3PO-tau and p-tau as well as a decrease of 3PO-tau
      related toxicity. In addition, we used the transgenic PrP(C) knockout (Prnp0/0)
      mouse line to study the dynamics of tau phosphorylation, an important
      pathological hallmark in the pathogenesis of AD in vivo. There, an effect of
      PrP(C) on tau expression could be observed under oxidative stress conditions but
      not during aging. In summary, we provide further evidence for interactions of
      PrP(C) with proteins that are known to be the key players in AD pathogenesis. We
      identified tau and its phosphorylated forms as potential PrP-interactors and
      report a novel protective function of PrP(C) in AD-like tau pathology.

PMID- 24028866
TI  - Serum folate, homocysteine, brain atrophy, and auto-CM system: The Treviso
      Dementia (TREDEM) study.
AB  - BACKGROUND: The role of folate and homocysteine in brain atrophy associated with
      Alzheimer's disease is not completely understood. OBJECTIVE: The aim of this
      study was to investigate the relationships between serum folate and homocysteine
      levels and the degree of cortical-subcortical and hippocampal atrophy in a first
      relatively preliminary sample of the Treviso Dementia (TREDEM) study using a
      potent data mining method. METHODS: Physiological data, biochemical parameters,
      clinical assessment data, brain atrophy severity assessed with CT scans, and
      neuropsycological and disability data were assessed in a group of 232 outpatients
      (93 men and 139 women, aged 40.2-100 years) enrolled in the TREDEM study carried
      out in Treviso (Italy). A semantic connectivity map obtained through the Auto-CM
      system, a fourth generation artificial neural network (ANN), was used to offer
      some insight regarding the complex biological connections between the studied
      variables and the degree of brain atrophy. RESULTS: Close associations between
      low serum folate levels and severe cortical-subcortical atrophy along with severe
      hippocampal atrophy measured by the width of the temporal horns of lateral
      ventricles were found. We also showed an association between high homocysteine
      levels and severe cortical-subcortical and hippocampal atrophy. CONCLUSION: The
      role of folate, which is inversely associated with the severity of brain atrophy,
      was confirmed. Our results also confirm the association between high homocysteine
      levels and severe cortical-subcortical and hippocampal atrophy. Auto-CM ANN is
      able to highlight associations sometimes visible only in longitudinal studies
      through intelligent data mining of a cross-sectional study.

PMID- 24028867
TI  - Endogenous tau aggregates in oligodendrocytes of rTg4510 mice induced by human
      P301L tau.
AB  - Tau belongs to the microtubule-associated family of proteins that maintain
      cytoskeletal structure by regulating microtubule dynamics. In certain
      neurodegenerative diseases termed tauopathies, tau is abnormally phosphorylated
      and accumulates as filamentous inclusions. Transgenic mouse models that
      overexpress human tau have been widely used to investigate tau pathogenesis.
      Although many studies have attempted to elucidate the pathological function of
      transgenic human tau, it remains unknown whether endogenous mouse tau is involved
      in disease progression. Here we generated an mTau antibody that selectively
      recognizes mouse and rat tau, but not human tau. In rTg4510 tau transgenic mice,
      we identified a higher molecular weight mouse tau (~60-kDa) in sarkosyl-insoluble
      fractions. mTau antibody started to recognize intracellular aggregates and thread
      like structures in 4- to 6-month-old rTg4510 mice. Tau inclusions appeared
      earlier, being detected in 2.5-month-old rTg4510 mice with MC1 antibody.
      Immunoelectron microscopy confirmed the presence of filamentous aggregates of
      mouse tau, which were abundant in oligodendrocytes but rare in neurons. Mouse tau
      inclusions in oligodendrocytes were confirmed by double-labeling with an
      oligodendrocyte marker. Our data indicate that mouse tau has potential
      aggregation properties in neurons and non-neurons. The mTau antibody will be
      useful for investigating the role of mouse tau in mouse models of tauopathy.

PMID- 24028868
TI  - Blood plasma IgG Fc glycans are significantly altered in Alzheimer's disease and
      progressive mild cognitive impairment.
AB  - Blood-based anti-amyloid-beta (Abeta) immunoglobulins (IgGs) and peripheral
      inflammation are factors correlating with development of Alzheimer's disease
      (AD). IgG functionality can drastically change from anti- to pro-inflammatory via
      alterations in the IgG-Fc N-glycan structure. Herein, we tested if IgG-Fc
      glycosylation in plasma is indeed altered during the development of AD. Samples
      from age-matched subjects of 23 controls, 58 patients with stable mild cognitive
      impairment (SMCI), 34 patients with progressive (P)MCI, and 31 patients with AD
      were investigated. Label-free shotgun proteomics was applied without glycoprotein
      enrichment. Glycans on peptides EEQYNSTYR (IgG1) and EEQFNSTFR (IgG2) were
      quantified, and their abundances were normalized to total IgGn glycoform
      abundance. Univariate and multivariate statistics were employed to investigate
      the correlations between the patients groups and the abundances of the IgG
      glycoforms as well as those of inflammatory mediating proteins. Significant
      differences (p <= 0.05) were found, with a lower abundance of complex
      galactosylated and sialylated forms in AD. For females, a decline in glycoform
      complexity correlated with disease progress but an inverse change was found in
      males prior to the onset of AD. Principal component analysis (PCA; Males:
      R(2)X(cum) = 0.65, Q(2)(cum) = 0.34; Females: R(2)X(cum) = 0.62, Q(2)(cum) =
      0.36), confirmed the gender similarities (for controls, SMCI and AD) as well as
      differences (for PMCI), and showed a close correlation between pro-inflammatory
      protein markers, AD, female PMCI, and truncated IgG-Fc glycans. The differences
      observed between genders prior to the onset of AD may indicate a lower ability in
      females to suppress peripheral inflammation, which may lead to exacerbated
      disease progression.

PMID- 24028869
TI  - Temperature-induced lipocalin (TIL) is translocated under salt stress and
      protects chloroplasts from ion toxicity.
AB  - Temperature-induced lipocalins (TIL) have been invoked in the defense from heat,
      cold and oxidative stress. Here we document a function of TIL for basal
      protection from salinity stress. Heterologous expression of TIL from the salt
      resistant poplar Populus euphratica did not rescue growth but prevented
      chlorophyll b destruction in salt-exposed Arabidopsis thaliana. The protein was
      localized to the plasma membrane but was re-translocated to the symplast under
      salt stress. The A. thaliana knock out and knock down lines Attil1-1 and Attil1-2
      showed stronger stress symptoms and stronger chlorophyll b degradation than the
      wildtype (WT) under excess salinity. They accumulated more chloride and sodium in
      chloroplasts than the WT. Chloroplast chloride accumulation was found even in the
      absence of salt stress. Since lipocalins are known to bind regulatory fatty acids
      of channel proteins as well as iron, we suggest that the salt-induced trafficking
      of TIL may be required for protection of chloroplasts by affecting ion
      homeostasis. 

PMID- 24028870
TI  - Prediction of conversion from mild cognitive impairment to Alzheimer disease
      based on bayesian data mining with ensemble learning.
AB  - Prediction of disease progress is of great importance to Alzheimer disease (AD)
      researchers and clinicians. Previous attempts at constructing predictive models
      have been hindered by undersampling, and restriction to linear associations among
      variables, among other problems. To address these problems, we propose a novel
      Bayesian data-mining method called Bayesian Outcome Prediction with Ensemble
      Learning (BOPEL). BOPEL uses a Bayesian-network representation with boosting, to
      allow the detection of nonlinear multivariate associations, and incorporates
      resampling-based feature selection to prevent over-fitting caused by
      undersampling. We demonstrate the use of this approach in predicting conversion
      to AD in individuals with mild cognitive impairment (MCI), based on structural
      magnetic-resonance and magnetic-resonance- spectroscopy data. This study includes
      26 subjects with amnestic MCI: the converter group (n = 8) met MCI criteria at
      baseline, but converted to AD within five years, whereas the non-converter group
      (n = 18) met MCI criteria at baseline and at follow-up. We found that BOPEL
      accurately differentiates MCI converters from non-converters, based on the
      baseline volumes of the left hippocampus, the banks of the right superior
      temporal sulcus, the right entorhinal cortex, the left lingual gyrus, and the
      rostral aspect of the left middle frontal gyrus. Prediction accuracy was 0.81,
      sensitivity was 0.63 and specificity was 0.89. We validated the generated
      predictive model with an independent data set constructed from the Alzheimer
      Disease Neuroimaging Initiative database, and again found high predictive
      accuracy (0.75). 

PMID- 24028871
TI  - Multiple Sclerosis Lesions in the Brain: Computer-Assisted Assessment of Lesion
      Load Dynamics on 3D FLAIR MR Images.
AB  - The detection and monitoring of brain lesions caused by multiple sclerosis is
      commonly performed with the use of magnetic resonance imaging. Analysis of a
      large number of images is a time-consuming challenge to the neuroradiologist,
      that can be accelerated with the assistance of computer-detection software. In 98
      baseline and follow-up brain magnetic resonance studies from 88 patients with a
      diagnosis of multiple sclerosis, we employed locally developed lesion-detection
      software to assess temporal change in the load of brain lesions and compared its
      results to routine clinical reports. Analyzing the differences between the follow
      up study and the baseline study, the software displays the results in the form of
      a scrollable axial volume, with the changed lesions highlighted in different
      colors and superimposed on the baseline reference scan. Disagreements between the
      software and the clinical readers in the detection of changed lesions were
      observed only in 11 (11.2%) cases, and the difference did not reach statistical
      significance (p=0.07). The mean interpretation time with assistance of the
      software was 2.7+/-2.2 minutes. We conclude that the performance of the software
      assisted interpretation in the analysis of change over time in multiple sclerosis
      brain lesions is comparable to the performance of clinical readers, with a
      possibly shorter assessment time. Our study demonstrates the potential of
      including lesion-detection software in the workflow of neuroradiology practice. 

PMID- 24028872
TI  - Early diffusion-weighted imaging findings in hypoxic-anoxic injury. A case series
      and review of the literature.
AB  - Anoxic brain injury can lead to death or permanent neurological defects involving
      memory, personality, vision, and language. It is well established that magnetic
      resonance imaging (MRI), specifically diffusion-weighted imaging (DWI), allows
      for earlier and more accurate diagnosis than computed tomography for this type of
      insult. Here we describe three cases of diffuse cerebral anoxia in which
      conventional MRI in the early subacute phase demonstrated near normal findings
      and abnormalities were most evident on DWI and apparent diffusion coefficient
      maps. The cases presented are unique and instructive as these abnormalities could
      be mistakenly interpreted as normal due to their uniform and symmetric
      appearance. 

PMID- 24028873
TI  - Fabry disease presenting with multiple hemorrhagic cerebral infarction. A case
      report.
AB  - We describe a 57-year-old woman, a heterozygote for Fabry disease who had
      multiple hemorrhagic cerebral infarctions. Her clinical course and radiological
      findings suggested cardiogenic cerebral embolus, but distinction from multiple
      cerebral infarction associated with Fabry disease seemed necessary. Our present
      case is reported with reference to the literature to introduce various types of
      stroke, which can develop in patients with Fabry disease. 

PMID- 24028874
TI  - Early appearance of diffusion-weighted hyperintensities in aphasic status
      epilepticus. A case report.
AB  - Partial status epilepticus rarely manifests mainly with global aphasia. It
      usually results in diffusion-weighted imaging (DWI) abnormalities after prolonged
      seizures. We discuss the magnetic resonance imaging (MRI) findings in a patient
      with aphasic status epilepticus. MRI showed diffusion restriction four hours
      after onset of symptoms. We summarize previously reported brain imaging findings
      in status epilepticus and discuss the purported mechanism behind these changes.
      Findings in our patient, similar to few others described in the literature,
      suggest that cortical DWI hyperintensities can occur shortly following aphasic
      status epilepticus. 

PMID- 24028875
TI  - Spontaneous regression of dilated virchow-robin spaces. A case report.
AB  - We describe a 28-year-old woman with a dilated perivascular spaces in the right
      pre-rolandic district. The purpose of this article is to provide an in-depth
      overview of the MR imaging features of VR spaces and to describe magnetic
      resonance imaging evidence of complete regression of dilated perivascular spaces
      (2). 

PMID- 24028876
TI  - Cerebral thromboembolism: value of susceptibility-weighted imaging in the initial
      diagnosis of acute infarction.
AB  - Susceptibility-weighted imaging (SWI) is commonly used to diagnose cerebral
      hemorrhage, calcification, and other T2* lesions. Its role in the detection of
      cerebral thromboemboli has been suggested for emboli of the anterior division of
      the middle cerebral artery (MCA). The purpose of our study was to determine SWI's
      accuracy and sensitivity in detection of all sites of cerebral thromboemboli, not
      just MCA emboli. Two neuroradiologists retrospectively reviewed consecutive MRI
      brain examinations with SWI for cerebral thromboemboli in 100 patients with
      clinical suspicion for stroke determined by the NIH Stroke Scale (NIHSS) score.
      FLAIR, MRA, CT, and catheter angiography were reviewed for thromboemboli in the
      same patients. Thromboembolic sites included: the internal carotid artery (ICA)
      terminus, anterior MCA, posterior MCA, any other cerebral artery, or if not
      present. The exclusion criteria included: no magnetic resonance angiogram (MRA)
      or catheter angiogram for comparison, lack of restricted diffusion, lacunar
      infarcts, and the presence of massive hemorrhage. The accuracy, sensitivity, and
      specificity of each imaging modality were determined. Twenty-four patients were
      excluded based on the aforementioned criteria. Cerebral thromboemboli were
      identified in 35 of the remaining 76 patients. Of the 35 patients with
      thromboemboli, 30 were identified on SWI. FLAIR detected 22/35 emboli, MRA 30/33,
      CT 18/35, and catheter angiography 12/12. The accuracies for SWI, FLAIR, and CT
      were 97%, 84%, and 74%, respectively. The sensitivities for SWI, FLAIR, and CT
      were 85%, 61%, and 52%, respectively. The specificities for SWI, FLAIR, and CT
      were 100%, 98%, and 93%, respectively. There is an adjunctive role of SWI to
      identify cerebral thromboemboli in patients with acute infarction. SWI is
      superior to FLAIR and CT, and complementary to MRA and catheter angiography in
      emboli detection. This study supports SWI detection of MCA emboli, but also
      emphasizes its utility in emboli detection of other arteries based on a high
      accuracy and sensitivity. 

PMID- 24028877
TI  - High-Grade Cerebral Glioma Characterization: Usefulness of MR Spectroscopy and
      Perfusion Imaging Associated Evaluation.
AB  - The aim of our study was to evaluate if both spectroscopy and perfusion magnetic
      resonance (MR) imaging are necessary to differentiate high grade gliomas from low
      grade tumour, or if only one of these techniques is sufficient. Sixty-five
      patients with cerebral glioma were retrospectively evaluated. All patients were
      studied both with spectroscopy and perfusion imaging. In 43 cases histological
      examination showed a high grade glioma while a low grade glioma was found in 22
      patients. For every patient spectroscopic maximum Cho/NAA ratio and lactate
      presence was established maximum relative CBV value was evaluated by perfusion
      MR. Both for Cho/NAA and rCBV threshold values were obtained by means of ROC
      curves. Then diagnostic sensitivity and specificity for high grade gliomas
      identification was evaluated for spectroscopic data only (Cho/NAA and lactate
      presence that was considered a high grade glioma marker), for perfusional data
      only (rCBV) and finally for both spectroscopic and perfusional data together.
      Sensitivity was significantly highest evaluating both spectroscopic and
      perfusional data together (89.7%) in comparison with spectroscopy (74.4%) or
      perfusion (79.4%) alone. Instead specificity was slightly lower with all data
      (91.7%) in comparison with spectroscopy (95.8%) and perfusion (95.8%) alone. In
      conclusion, to characterize high grade gliomas it is more useful to evaluate
      spectroscopic and perfusional data together with respect only one of these
      techniques alone. 

PMID- 24028878
TI  - Brain Metastases from Different Primary Carcinomas: an Evaluation of DSC MRI
      Measurements.
AB  - This study evaluated the roles of different dynamic susceptibility contrast
      magnetic imaging (DSC MRI) measurements in discriminating between brain
      metastases derived from four common primary carcinomas. Thirty-seven patients
      with brain metastases were enrolled. Relative cerebral blood volume (rCBV),
      cerebral blood flow (rCBF) and relative mean transit time (rMTT) in both tumor
      and peritumoral edema were measured. Metastases were grouped by their primary
      tumor (lung, gastrointestinal, breast and renal cell carcinoma). DSC MRI
      measurements were compared between groups. Mean rCBV, rCBF, rMTT in tumor and
      peritumoral edema of all brain metastases (n=37) were 2.79 +/- 1.73, 2.56 +/-
      2.11, 1.21 +/- 0.48 and 1.05 +/- 0.53, 0.86 +/- 0.40, 1.99 +/- 0.41,
      respectively. The tumoral rCBV (5.26 +/- 1.89) and rCBF (5.32 +/- 3.28) of renal
      metastases were greater than those of the other three metastases (P<0.05). The
      tumoral rMTT (1.58 +/- 0.77) of breast metastases was statistically greater than
      that (0.96 +/- 0.31) of gastrointestinal metastases (P=0.013). No statistical
      difference was found between peritumoral rCBV, rCBF and rMTT (P>0.05). Evaluating
      various DSC MRI measurements can provide complementary hemodynamic information on
      brain metastases. The tumoral rCBV, rCBF and likely rMTT can help discriminate
      between brain metastases originating from different primary carcinomas. The
      peritumoral DSC MRI measurements had limited value in discriminating between
      brain metastases. 

PMID- 24028879
TI  - Congenital X-linked Stapes Gusher Syndrome in an Infant. A Case Report.
AB  - Congenital X-linked deafness with stapes gusher is a rare, but well-known
      clinical entity with characteristic radiological features. Recognition of these
      findings is important as it changes the treatment course and precludes
      stapedectomy, which if done can lead to stapes gusher in these patients. We
      present the case of a nine-month-old male infant with hearing loss. CT scan
      showed typical radiological features of X-linked stapes gusher syndrome. In
      addition, the superior semicircular canals appeared dehiscent which could be due
      to immature ossification or less likely due to defective development as part of
      the disease. To the best of our knowledge this is the youngest patient
      prospectively identified by imaging in the English medical literature. 

PMID- 24028880
TI  - Childhood Ataxia with Cerebral Hypomyelination Syndrome: a Variant of Patient
      with Early Childhood Onset Related to EIF2B3 Mutation. A Case Report.
AB  - Childhood ataxia with central nervous system hypomyelination (CACH) syndrome is
      an autosomal recessive transmitted leukodystrophy characterised by early
      childhood onset and acute deterioration following febrile illnesses or head
      trauma. We describe the case of a child with early onset of CACH syndrome. He
      presented with cerebellar ataxia beginning around two years of age with mild
      mental retardation. MRI showed diffuse white matter signal changes with thinning
      of the corpus callosum. 

PMID- 24028881
TI  - Leukocoria in a child with sturge-weber syndrome.
AB  - A five-year-old girl with Sturge-Weber syndrome (SWS) presented with unilateral
      leukocoria. Imaging excluded retinoblastoma and revealed a choroidal hemangioma,
      a non-traumatic vitreous hemorrhage and a cataract. To the best of our knowledge,
      this is the first case report in the radiologic literature of these
      ophthalmologic findings presenting together and conditioning leukocoria in the
      setting of SWS. We discuss possible mechanisms and review the literature,
      emphasizing the role of neuroimaging in pediatric patients with SWS and
      ophthalmologic complaints. 

PMID- 24028882
TI  - Unilateral Basal Ganglia Infarcts: a Red Flag for Ipsilateral Cranio-Cervical
      Arterial Occlusive Disease. A Report on Two Children with Moya-moya Disease.
AB  - Steno-occlusive disease of the internal carotid arteries and/or the circle of
      Willis with development of collateral perforator vessels attempting to supply
      under-perfused parenchyma are the basis for moya-moya phenomenon with the classic
      "puff of smoke" appearance on cerebral angiogram. We describe two cases of moya
      moya with unilateral macroangiopathy of the internal carotid artery and
      ipsilateral middle cerebral artery in two 11-year-old girls: a Down's syndrome
      patient, and a second idiopathic patient. The arteriopathy in our cases differs
      from typical or classically described moya-moya disease in that it was
      exclusively unilateral rather than symmetric and bilateral. The association of
      predominant deep grey matter (basal ganglia) strokes in children with coexisting
      ipsilateral parainsular infarcts, as in our cases, is potentially a red flag for
      ipsilateral macroangiopathy. 

PMID- 24028883
TI  - A Simple and Fast Method of 3D Registration and Statistical Landmark Localization
      for Sparse Multi-Modal/Time-Series Neuroimages Based on Cortex Ellipse Fitting.
AB  - Existing methods of neuroimage registration typically require high quality scans
      and are time-consuming. We propose a simple and fast method which allows intra
      patient multi-modal and time-series neuroimage registration as well as landmark
      identification (including commissures and superior/inferior brain landmarks) for
      sparse data. The method is based on elliptical approximation of the brain
      cortical surface in the vicinity of the midsagittal plane (MSP). Scan
      registration is performed by a 3D affine transformation based on parameters of
      the cortex elliptical fit and by aligning the MSPs. The landmarks are computed
      using a statistical localization method based on analysis of 53 structural scans
      without detectable pathology. The method is illustrated for multi-modal
      registration, analysis of hemorrhagic stroke time series, and ischemic stroke
      follow ups, as well as for localization of hardly visible or not discernible
      landmarks in sparse neuroimages. The method also enables a statistical
      localization of landmarks in sparse morphological/non-morphological images, where
      landmark points may be invisible. 

PMID- 24028884
TI  - Atlas-Based Classification of Hyperintense Regions from MR Diffusion-Weighted
      Images of the Brain: Preliminary Results.
AB  - The study of subjects with acquired brain damage in a specific location is
      important in exploring human brain function. Description of lesion locations
      within and across subjects is a crucial methodological component that usually
      involves the distinction of normal from damaged tissue (lesion segmentation) in
      relation to lesion locations in terms of a standard anatomical reference space
      (lesion mapping). Our study provides an atlas-based, computer-aided methodology
      for classification of hyperintense regions on diffusion-weighted images of the
      brain, representing either ischemic lesions or susceptibility artifacts. We
      applied a leave-one-out method of cross-validation that computed probabilistic
      atlases of true lesions and artifacts, based on training data. Our approach
      accurately classifies lesions and artifacts, but leaves a significant number of
      regions unclassified, due to the relatively small number of training samples. An
      initial segmentation step based on a larger sample of data sets is required to
      automate discrimination of lesions and artifacts. 

PMID- 24028885
TI  - Presurgical Identification of the Central Sulcus Using GE EPI Sequences in
      Combination with 3D Reconstruction is a Useful and Easy Technique for Functional
      Identification of the Sensorimotor Cortex.
AB  - Functional magnetic resonance imaging (fMRI) is a noninvasive neuroimaging
      technique that enables the visualization of vascular changes originating in the
      cortex on the execution of a simple motor task. We aimed to assess the usefulness
      of sensorimotor fMRI using echo-planar imaging (EPI) techniques and assess its
      clinical usefulness in the identification of the central sulcus. We studied 32
      candidates for neurosurgery who had centrally located space-occupying lesions
      with fMRI using EPI images with blood oxygen level-dependent (BOLD) gradient-echo
      (GE) sequences acquired on a 1.5T scanner while patients repeatedly opened and
      closed their hands. Statistical activation images (t images) corresponding to the
      movements of the right and left hands were compared using cancellation analysis.
      Three-dimensional reconstruction of the cranium and brain of each patient showed
      the relative position of the expansive lesion and of non-damaged cortical tissue.
      Reproducible and selective functional sensorimotor activation was observed in 32
      patients. Validation was carried out by intraoperative mapping in 19 patients.
      Based on intraoperative confirmation data we assumed that functional MR imaging
      (fMRI) is a valid method for identifying the motor cortex. Nevertheless, a
      limitation to our study is that not all the patients received invasive cortical
      stimulation. It is also relevant to indicate that fMRI and intraoperative
      procedures coincide in the sulcus identified as the sensorimotor cortex.
      Neurological examination did not reveal postoperative motor/sensitive
      deterioration in the remaining patients. fMRI using GE EPI sequences in
      combination with three-dimensional reconstruction is a useful and easy technique
      for functional identification of the sensorimotor cortex. 

PMID- 24028886
TI  - Endovascular management of direct carotid-cavernous sinus fistulas.
AB  - To evaluate the single-centre experience with endovascular management of direct
      carotid-cavernous sinus fistulas (DCCF). Between November 2008 and November 2010,
      a total of 14 patients (11 males) with direct carotid-cavernous sinus fistula
      underwent 16 transarterial treatment sessions. The patient files and angiograms
      were analysed retrospectively. Clinical signs and symptoms included exophthalmos
      [n=12, (85.7%)], pulsatile tinnitus [n=9, (64.3%)], cranial nerve III or VI palsy
      [n=2, (14.3%)], and impaired vision [n=1, (7.1%)]. Angiography revealed in
      addition cortical drainage in five patients (35.7%). Transarterial embolization
      was performed using detachable balloon in nine sessions (56.2%), detachable coils
      in three sessions (18.8%) and a combination with Onyx in four sessions (25%).
      Complete interruption of the arteriovenous shunt was achieved in all patients.
      There was a tendency for ocular pressure-related symptoms to resolve rapidly,
      while cranial nerve palsy and diplopia improved slowly (7.1%) or did not change
      (7.1%). The patient with visual impairment recovered within the first two weeks
      after endovascular treatment. After complete interruption of the arteriovenous
      shunt, two (12.5%) recurrences were observed in balloon treatment and retreatment
      was given. Transarterial management is a highly efficient and safe treatment in
      DCCFs. In the majority of patients a significant and permanent improvement in
      clinical signs and symptoms can be achieved. 

PMID- 24028887
TI  - Letter to the editor.

PMID- 24028888
TI  - Endoscopic ultrasound-guided fine needle aspiration as a diagnostic and staging
      tool for rectal and perirectal lesions-an institutional experience.
AB  - The role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in
      evaluating lesions adjacent to the upper gastrointestinal tract wall is well
      established. However, this tool is underused in evaluating rectal and perirectal
      lesions, possibly due to insufficient experience and underrecognized value of
      this procedure. In this study, we report our institutional experience with EUS
      FNA as a diagnostic and staging tool for rectal and perirectal lesions. A
      retrospective chart review was performed and a cohort of 38 patients who
      underwent rectal EUS-FNA (41 specimens) at our institution between January 2002
      and July 2012 was retrieved. The cytology diagnoses were compared with the
      concurrent or follow-up histologic and clinical diagnoses. Among the total 41
      cases, rectal EUS-FNA was performed as a diagnostic procedure in 22 (54%) and a
      staging procedure in 19 (46%) cases. On cytology examination, 18 cases (44%) were
      diagnosed as malignant; 1 (2%), as atypical/suspicious for malignancy; 3 (7%), as
      benign neoplastic; 13 (32%), as nonneoplastic; and 6 (15%), as nondiagnostic
      cases. Concurrent or follow-up histologic diagnoses were available in 20 cases
      (48%), 19 of them had concordant cytological/histologic findings (10 benign, 9
      malignant). One perirectal lymph node with negative cytology diagnosis was found
      to be positive on histologic examination, probably due to sampling error on
      cytology. The sensitivity and specificity of EUS-FNA for detecting malignant
      rectal/perirectal lesions in this study were 91% and 100%, respectively.
      Endoscopic ultrasound-guided fine needle aspiration is a useful diagnostic tool
      for rectal/perirectal lesions; it confirms or excludes malignancy for lesions
      with high or low clinical suspicions. It serves as a reliable staging method to
      identify patients for proper clinical management.

PMID- 24028889
TI  - Mapping 'partially resistant', 'fully resistant', and 'super resistant' malaria.
AB  - Sulfadoxine-pyrimethamine (SP) is used throughout Africa for intermittent
      preventive treatment (IPT) of malaria, but resistance threatens its efficacy. We
      found marked regional differences in the genotypes responsible for SP resistance
      when mapping recent surveys of dihydrofolate reductase (dhfr) and dihydropteroate
      synthase (dhps) mutations. In West Africa, a 'partially resistant' combination of
      dhfr N51I, N59R, and S108N with dhps A437G predominates, whereas in East Africa
      the 'fully resistant' combination of dhfr N51I, N59R, and S108N with dhps
      A437G+K540E is found. There are three East African foci where 'fully resistant'
      populations have additionally acquired dhps 581G and/or dhfr 164L to become
      'super resistant'. SP-IPT in infants and pregnant women is reported to have
      failed in super resistant areas prompting review of SP-IPT use in affected areas.

PMID- 24028891
TI  - Epigenetic consequences of a changing human diet.
AB  - The human diet has undergone profound changes over recent generations and this
      trend is likely to accelerate in the 21st century. Innovations in food
      technology, new ways of producing and processing foods and the increasing use of
      artificial vitamins and novel ingredients are changing the human diet in ways
      that our dietary monitoring systems struggle to keep pace with. There is a
      growing awareness of the importance of diet, but little understanding of how
      these changes may affect the health of current and future generations. Epigenetic
      programming, and specifically the persistence of functional epigenetic states
      following nutritional exposure, is particularly relevant to the issue of dietary
      change. Epigenetics is emerging as perhaps the most important mechanism through
      which diet and nutrition can directly influence the genome and there is now
      considerable evidence for nutritional epigenetic programming of health and the
      response to diet itself. A number of nutrients and food components that are
      changing in the human diet have been shown to produce epigenetic states that are
      stable across different timescales. We need to better understand the nutritional
      programming of epigenetic states, the persistence of these marks in time and
      their effect on biological function and the response to diet.

PMID- 24028890
TI  - Initial development of a temporal-envelope-preserving nonlinear hearing aid
      prescription using a genetic algorithm.
AB  - Most hearing aid prescriptions focus on the optimization of a metric derived from
      the long-term average spectrum of speech, and do not consider how the prescribed
      values might distort the temporal envelope shape. A growing body of evidence
      suggests that such distortions can lead to systematic errors in speech
      perception, and therefore hearing aid prescriptions might benefit by including
      preservation of the temporal envelope shape in their rationale. To begin to
      explore this possibility, we designed a genetic algorithm (GA) to find the
      multiband compression settings that preserve the shape of the original temporal
      envelope while placing that envelope in the listener's audiometric dynamic range.
      The resulting prescription had a low compression threshold, short attack and
      release times, and a combination of compression ratio and gain that placed the
      output signal within the listener's audiometric dynamic range. Initial behavioral
      tests of individuals with impaired hearing revealed no difference in speech-in
      noise perception between the GA and the NAL-NL2 prescription. However, gap
      detection performance was superior with the GA in comparison to NAL-NL2. Overall,
      this work is a proof of concept that consideration of temporal envelope
      distortions can be incorporated into hearing aid prescriptions. 

PMID- 24028892
TI  - On the derivation of a tensor to calculate six degree-of-freedom, musculotendon
      joint stiffness: implications for stability and impedance analyses.
AB  - Major joints, such as the knee, shoulder, and spine, can buckle along the
      translational degrees-of-freedom (DoF), causing injury to ligaments and other
      passive tissues. Despite this, stability and impedance analyses have focused
      primarily on the rotational DoF. As such, mathematical models quantifying
      musculotendon translational stiffnesses remain limited and, to our knowledge,
      there are no published works that explicitly describes the interactions between
      DoF. Using an energy approach, we derived a six DoF stiffness tensor and provided
      the necessary equations needed to quantify the musculotendon stiffness of any
      joint. Using a knee model, we then compared the derived stiffness tensor against
      two commonly used measures: one that excludes translational DoF and another that
      excludes interactions between DoF. We found that both of these measures had large
      over-estimations of stiffness, particularly for the rotational DoF, compared to
      our derived tensor. These findings indicate that previous analyses may have found
      rotational DoF to be stable when they were unstable. 

PMID- 24028894
TI  - Combination of siRNA-directed Kras oncogene silencing and arsenic-induced
      apoptosis using a nanomedicine strategy for the effective treatment of pancreatic
      cancer.
AB  - The synergetic inhibitory effects on human pancreatic cancer by nanoparticle
      mediated siRNA and arsenic therapy were investigated both in vitro and in vivo.
      Poly(ethylene glycol)-block-poly(L-lysine) were prepared to form siRNA-complexed
      polyplex and poly(ethylene glycol)-block-poly(DL-lactide) were prepared to form
      arsenic-encapsulated vesicle, respectively. Down-regulation of the mutant Kras
      gene by siRNA caused defective abilities of proliferation, clonal formation,
      migration, and invasion of pancreatic cancer cells, as well as cell cycle arrest
      at the G0/G1 phase, which substantially enhanced the apoptosis-inducing effect of
      arsenic administration. Consequently, co-administration of the two nanomedicines
      encapsulating siRNA or arsenic showed ideal tumor growth inhibition both in vitro
      and in vivo as a result of synergistic effect of the siRNA-directed Kras oncogene
      silencing and arsenic-induced cell apoptosis. These results suggest that the
      combination of mutant Kras gene silencing and arsenic therapy using nanoparticle
      mediated delivery strategy is promising for pancreatic cancer treatment. FROM THE
      CLINICAL EDITOR: Treatment of pancreatic cancer remains a major challenge. These
      authors demonstrate a method that combines a siRNA-based Kras silencing with
      arsenic delivery to pancreatic cancer cells using nanoparticles, resulting in
      enhanced apoptosis induction in the treated cells.

PMID- 24028893
TI  - Enhanced tumor delivery and antitumor activity in vivo of liposomal doxorubicin
      modified with MCF-7-specific phage fusion protein.
AB  - A novel strategy to improve the therapeutic index of chemotherapy has been
      developed by the integration of nanotechnology with phage technique. The
      objective of this study was to combine phage display, identifying tumor-targeting
      ligands, with a liposomal nanocarrier for targeted delivery of doxorubicin.
      Following the proof of concept in cell-based experiments, this study focused on
      in vivo assessment of antitumor activity and potential side-effects of phage
      fusion protein-modified liposomal doxorubicin. MCF-7-targeted phage-Doxil
      treatments led to greater tumor remission and faster onset of antitumor activity
      than the treatments with non-targeted formulations. The enhanced anticancer
      effect induced by the targeted phage-Doxil correlated with an improved tumor
      accumulation of doxorubicin. Tumor sections consistently revealed enhanced
      apoptosis, reduced proliferation activity and extensive necrosis. Phage-Doxil
      treated mice did not show any sign of hepatotoxicity and maintained overall
      health. Therefore, MCF-7-targeted phage-Doxil seems to be an active and tolerable
      chemotherapy for breast cancer treatment. FROM THE CLINICAL EDITOR: The authors
      of this study successfully combined phage display with a liposomal nanocarrier
      for targeted delivery of doxorubicin using MCF-7-targeted phage-Doxil
      nanocarriers in a rodent model. The method demonstrated improved efficiency and
      reduced hepatotoxicity, paving the way to future clinical trials addressing
      breast cancer.

PMID- 24028895
TI  - Ectopic calcification: importance of common nanoparticle scaffolds containing
      oxidized acidic lipids.
AB  - The term nanobacteria, sometimes referred to as nanobacteria-like particles
      (NLPs), is presently recognized as a misnomer for inert calcified nanoparticles.
      However, misinterpretation of its propagation as a living organism still
      continues. Ultrastructural and elemental analyses, combining immuno-electron
      microscopy with an original NLP isolate (P-17) derived from urinary stones, and
      an IgM monoclonal antibody (CL-15) raised against P-17 have now revealed that,
      oxidized lipids with acidified functional groups were key elements in NLP
      propagation. Lamellar structures composed of acidic/oxidized lipids provided
      structural scaffolds for carbonate apatite crystals. During in vitro culture,
      lipid peroxidation induced by gamma-irradiation of FBS was a major cause of
      accelerated NLP propagation. In pathological tissue samples from hyperlipidemic
      atherosclerosis-prone mice, CL-15 co-localized with fatty plaques, macrophage
      infiltrates and osteocalcin staining of aortic valve lesions. These observations
      indicate that naturally occurring NLP composed of mineralo-oxidized lipids
      complexes are generated as by-products rather than etiological agents of chronic
      inflammation. FROM THE CLINICAL EDITOR: The term "nanobacteria-like particles
      (NLPs)" is presently recognized as a misnomer for inert calcified nanoparticles
      as opposed to living organisms. This study convincingly demonstrates that
      naturally occurring NLPs composed of mineralo-oxidized lipid complexes are
      generated as by-products rather than etiological agents of chronic inflammation.

PMID- 24028897
TI  - Genomic analyses of the Formosan harvest mouse (Micromys minutus) and comparisons
      to the brown Norway rat (Rattus norvegicus) and the house mouse (Mus musculus).
AB  - The harvest mouse, Micromys minutus (MMIN), has a very wide range of distribution
      (from the British Isles across the Euroasian continent to Japan and Taiwan). We
      studied an isolated population of MMIN in Taiwan, which is at the southeastern
      margin of the species' geographic distribution, and compared its genetic
      complement with those of the same species previously reported from other
      geographic locations and with two model rodent species, the house mouse (Mus
      musculus) and the brown Norway rat (Rattus norvegicus). The diploid number (2N)
      of MMIN was 68, consistent with that reported for other populations. However,
      variations were noted in the fundamental number (FN) and the shape and banding
      patterns of the individual chromosomes among populations. The FN of MMIN was
      estimated to be 72, including 2 bi-armed autosomes, 31 one-armed autosomes, and
      one pair of one-armed sex chromosomes. Here, we propose the first ideogram for
      MMIN. C-banding, Ag-NOR, and the locations of 18S rRNA gene sequences (MMIN
      chromosomes no. 10, 14, 19, 29, 31, 33, and X) mapped by fluorescence in situ
      hybridization (FISH) are also reported. Additionally, we compared the 18S rDNA
      sequences and performed cross-species X chromosome painting (FISH) for M.
      minutus, M. musculus, and R. norvegicus. The results indicate that both genetic
      elements are rather conserved across species. Thus, implications for the
      phylogenetic position of Micromys were limited.

PMID- 24028898
TI  - Low rates of automatic reporting of estimated glomerular filtration rate in
      Southern Brazilian laboratories.
AB  - OBJECTIVES: The aim of this study was to evaluate the rate of eGFR reporting in
      Southern Brazilian laboratories. DESIGN AND METHODS: The eGFR automatic
      reporting, as assessed by Modification of Diet in Renal Disease (MDRD) and/or
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based
      equations, was evaluated in a representative cross-sectional sample. A
      standardized questionnaire to obtain this information was given out by mail or
      email. RESULTS: Five-hundred fifty laboratories, evenly distributed in the
      different state regions, completed the questionnaire. The eGFR was automatically
      reported by 54 (9.8%) laboratories, and the MDRD was the most commonly used
      equation (94.5%). The Jaffe methods were the most employed technique (94%) to
      measure serum creatinine. CONCLUSION: The automatic eGFR reporting rate was
      unacceptably low, emphasizing the crucial role of educating medical teams and
      laboratories on the importance of having these tools available to optimize
      detection of renal disease and proper treatment.

PMID- 24028899
TI  - Glomerular filtration rate as a determinant of free light chains in renal
      transplantation.
AB  - BACKGROUND: Transplant patients have an increased incidence of
      lymphoproliferative disorders. The development of a sensitive immunoassay for
      serum free light chain (sFLC) determination has improved the diagnosis of
      monoclonal gammapathy. However, metabolism of FLC largely depends on renal
      function which could lead to misinterpretation of results. The aim of this study
      was to assess polyclonal FLC in kidney transplant recipients in relation to
      markers of renal function. MATERIALS AND METHODS: 97 renal transplant patients
      (median transplantation follow-up of 2.2 years) were included in this study.
      Kappa FLC, lambda FLC and cystatin C were measured by particle-enhanced
      turbidimetric immunoassay (PETIA) using kits from a Binding Site (Birmingham, UK)
      SPAPLUS((r)) analyzer. Glomerular filtration rate was measured using urinary
      clearance of (99m)Tc-DTPA and estimated using CKD-EPI creatinine 2009, CKD-EPI
      cystatin C 2012 and CKD-EPI creatinine-cystatin C 2012. RESULTS: Serum kappa FLC
      was 22.38 [6.39-68.91] mg/L and serum lambda FLC was 15.66 [7.29-50.81] mg/L.
      Both levels of kappa and lambda were correlated with renal function. Median
      kappa/lambda ratio was 1.34 [0.57 to 2.67] leaving 19.6% of renal transplant
      patients outside the normal reference range [0.26-1.65]. However, using a
      reference interval normalized by renal function [0.37-3.1], none of our patients
      was classified as abnormal. CONCLUSION: kappa/lambda ratio should be cautiously
      analyzed in renal transplantation and renal function, estimated by
      creatinine/cystatin C equations should be taken into account.

PMID- 24028896
TI  - Recent development of silica nanoparticles as delivery vectors for cancer imaging
      and therapy.
AB  - In spite of significant advances in early detection and combined treatments, a
      number of cancers are often diagnosed at advanced stages and thereby carry a poor
      prognosis. Developing novel prognostic biomarkers and targeted therapies may
      offer alternatives for cancer diagnosis and treatment. Recent rapid development
      of nanomaterials, such as silica based nanoparticles (SiNPs), can just render
      such a promise. In this article, we attempt to summarize the recent progress of
      SiNPs in tumor research as a novel delivery vector. SiNP-assisted imaging
      techniques are used in cancer diagnosis both in vitro and in vivo. Meanwhile,
      SiNP-mediated drug delivery can efficiently treat tumor by carrying
      chemotherapeutic agents, photosensitizers, photothermal agents, siRNA, and gene
      therapeutic agents. Finally, SiNPs that contain at least two different functional
      agents may be more powerful for both tumor imaging and therapy. FROM THE CLINICAL
      EDITOR: This paper summarizes recent progress on the field of silica
      nanoparticles research as novel delivery vectors for cancer-specific imaging as
      well as drug delivery of chemotherapeutics, photosensitizers, photothermal
      agents, siRNA, and gene therapy agents.

PMID- 24028900
TI  - Water bath hyperthermia reduces stemness of colon cancer cells.
AB  - OBJECTIVES: Researchers have proposed that cancer stem cells (CSCs) are the
      driving force of tumorigenesis, recurrence, and metastases, contributing to the
      failure of some cancer treatments. Water bath hyperthermia, a novel treatment for
      cancer, can be highly effective when combined with chemotherapy, radiotherapy, or
      immunotherapy. Side population (SP) cells are part of a subpopulation of cells
      that have stem cell-like characteristics. In preliminary experiments, we
      discovered a decrease in SP cells in heat-treated colon cancer cells, which
      encouraged us to investigate whether hyperthermia had in fact played a role in
      regulating the stemness of colon cancer cells. DESIGN AND METHODS: We determined
      the number of SP cells and CD133-positive cells using flow cytometry; surveyed
      the expression of stemness-related genes and proteins by using quantitative
      reverse transcriptase-polymerase chain reaction and Western blot analysis,
      respectively; and evaluated tumor formation ability by using the tumor sphere
      formation assay. RESULTS: We found that water bath hyperthermia at 40  degrees C
      results in a decreased percentage of SP cells (i.e. decreased from 0.6% to 0.0%
      and 1.1% to 0.1% among heat-treated HCT116 cells and SW620 cell respectively) and
      CD133-positive cells (i.e. decreased from 25.1 +/- 1.2% to 18.7 +/- 1.3% and 33.6
      +/- 3.2% to 23.5 +/- 2.5% among heat-treated HCT116 cells and SW620 cell
      separately), weakens stem cell self-renewal properties (i.e., tumor colony
      formation ability), and downregulates the expression of stem-like cellular
      markers in colon cancer cells. CONCLUSIONS: All the findings indicate that
      hyperthermia has an important effect on the stemness of colon cancer cells.

PMID- 24028901
TI  - Impaired paraoxonase-1 status in obese children. Relationships with insulin
      resistance and metabolic syndrome.
AB  - OBJECTIVES: To investigate the relationships between serum paraoxonase-1 (PON1),
      insulin resistance, and metabolic syndrome (MetS) in childhood obesity. DESIGN
      AND METHODS: We studied 110 obese children and 36 non-obese children with a
      similar gender and age distribution. We measured serum PON1 activity against 5
      thiobutyl butyrolactone (TBBLase) and against paraoxon (paraoxonase). PON1
      concentration was measured separately as were the levels of several standard
      metabolic variables. The homeostasis model assessment (HOMA) index was calculated
      as an estimate of insulin resistance. RESULTS: TBBLase was significantly
      decreased in obese children (P=0.008), while paraoxonase activity and PON1
      concentrations showed non-significant trends towards decrease and increase,
      respectively (P=0.054 and P=0.060). TBBLase and paraoxonase specific activities
      were significantly decreased (P=0.004 and P=0.018, respectively). TBBLase
      specific activity was inversely associated with BMI, percentage body fat,
      insulin, HOMA, triglycerides, and C-reactive protein, and directly associated
      with HDL-cholesterol. Paraoxonase specific activity showed similar associations
      with BMI, percentage fat, HDL-cholesterol, and C-reactive protein. Obese children
      with MetS had lower TBBLase activities than obese children without MetS
      (P=0.018). Linear regression analyses showed that TBBLase was independently
      associated with HDL-cholesterol, BMI, percentage body fat and PON155
      polymorphism, but paraoxonase activity was associated only with PON1192
      polymorphism. CONCLUSIONS: Our results suggest that PON1 may play a role in the
      onset and development of metabolic alterations in childhood obesity leading to
      diabetes and cardiovascular disease later in life. However, being derived from
      statistical association study, this finding cannot be seen as showing cause
      effect.

PMID- 24028902
TI  - Spectrophotometric quantification of total urinary porphyrins as a screening test
      for porphyrias: threshold value revisited.
AB  - OBJECTIVES: The quantification of total urinary porphyrins based on
      spectrophotometry or spectrofluorimetry is a key screening test in cutaneous or
      mixed porphyria, performed before the quantitative fractionation of porphyrin
      isomers by chromatography. The aim of the present study was to determine the best
      threshold value for a spectrophotometric screening test and to estimate its
      diagnostic performances. DESIGN AND METHODS: Data from samples sent to the
      laboratory between January 2006 and July 2013 from patients with a suspicion of
      cutaneous or mixed porphyria were retrospectively collected. The final diagnosis
      was based on the clinical presentation and biochemical results performed on
      appropriate specimens. Control samples were obtained from 91 non-porphyria
      patients and 58 healthy individuals and patient samples were obtained from 38
      patients with symptomatic porphyria. The sensitivity and specificity of the
      spectrophotometric screening test were calculated at different cutoff values
      expressed in nmol/L and nmol/mmol creatinine using receiver operator curves.
      RESULTS AND CONCLUSION: A threshold of 18.8nmol/mmol creatinine was considered as
      the best cutoff value for the screening test, achieving a sensitivity of 100% and
      a specificity of 93.2%.

PMID- 24028903
TI  - Optimization of an HPLC method for phenylalanine and tyrosine quantization in
      dried blood spot.
AB  - OBJECTIVES: Patients affected by Phenylketonuria (PKU) require lifelong
      management based on phenylalanine (Phe) and tyrosine (Tyr) restricted intake or
      tetrahydrobiopterin (BH4) administration. Frequent monitoring of blood
      concentration of both amino acids during treatment is the key point for
      clinicians to achieve the best long-term neuropsychological outcome. RESULTS: The
      present study develops and validates a rapid and simple method for Phe and Tyr
      quantization in dried blood spot (DBS) since this specimen has the advantage of
      being low invasive, easily withdrawn even at home and stable if mail-delivered.
      The validation studies showed the robustness of the method. CONCLUSIONS: Serum
      and DBS samples from PKU patients were analyzed and compared, finding a good
      correlation of Phe and Tyr concentrations between the two different matrixes.

PMID- 24028904
TI  - QTLs influencing IGF-1 levels in a LOU/CxFischer 344F2 rat population. Tracks
      towards the metabolic theory of Ageing.
AB  - OBJECTIVE: Since a reduction of the insulin/IGF-1 signaling cascade extends life
      span in many species and IGF-1 signaling might partly mediate the effects of
      caloric restriction (CR), an experimental intervention for increasing longevity,
      the purpose of the present study was to use quantitative trait loci (QTL)
      analysis, an unbiased genetic approach, to identify particular regions of the
      genome influencing plasma IGF-1 levels in an F2 intercross between F344 and LOU/C
      rats; the latter being an inbred strain of Wistar origin, considered as a model
      of healthy aging since it resists to age (and diet)-induced obesity. DESIGN: F1
      hybrids were obtained by crossbreeding LOU/C with F344 rats, and then F1 were
      bred inter se to obtain the F2 population, of which 93 males and 94 females were
      studied. Total plasma IGF-1 levels were determined by radioimmunoassay. A genome
      scan of the F2 population was made with 100 microsatellite markers) selected for
      their polymorphism between LOU/C and F344 strains (and by covering evenly the
      whole genome. RESULTS: By simple interval mapping sex-dependent QTLs were found
      on chromosome 17 in males and on chromosome 18 in females. By multiple interval
      mapping, additional QTLs were found on chromosomes 1, 4, 5, 6, 12, 15 and 19 in
      males and on chromosomes 3, 5, 6, 12 and 17 in females. Only the markers D1Rat196
      and D12Mgh5 were found in both males and females. The majority of QTLs
      corresponded to metabolic syndrome (cardiac function: n = 45 (30%),
      obesity/diabetes: n = 22 (15%), inflammation: n = 19 (13%) and only a limited
      number to body weight: n = 13 (9%), proliferation (n = 10 (7%) or ossification: n
      = 7 (5%). Ninety-six candidate genes were located on the different QTLs. A
      significant proportion of these genes are connected to IGF-1 production and
      receptor pathways (n = 18) or metabolic syndrome (n = 11). CONCLUSIONS:
      Subsequent studies are necessary to determine whether the genetic networks
      underscored are also involved in age-associated obesity, diabetes and
      inflammation as well as cardiovascular impairments.

PMID- 24028905
TI  - Allergen immobilisation and signal amplification by quantum dots for use in a
      biosensor assay of IgE in serum.
AB  - The production of biosensors for point of care diagnostics usually requires the
      immobilisation and storage of protein (for example, antigen or antibody) on a
      sensor surface, in a manner that retains a high degree of activity and low levels
      of non-specific binding. These characteristics have been assessed for polymer
      immobilised antigens (allergens) using an IgG binding assay and demonstrated
      further by assay with serum containing reactive IgEs. The activity of allergens
      immobilised on sensor chips using copoly(DMA-NAS-MAPS) and a spotting technique,
      as well as the specificity of their binding interactions with cognate
      immunoglobulins was assessed using Dual Polarisation Interferometry (DPI). The
      data obtained indicate that the allergens studied remain stable over long periods
      of time (at least 114 days). This performance compared favourably with other
      immobilisation methods. Allergen coated chips were tested in an anti-casein IgE
      assay using human serum from allergic and non-allergic donors. Detection of both
      total Ig and specific IgE was demonstrated using a secondary anti-IgE antibody.
      Furthermore, optical signal enhancement with streptavidin conjugated quantum dots
      was shown to yield responses for samples below 0.84 ng/mL (0.35 KU/L) of IgE,
      which overlap with the industrial quasi-standard ImmunoCAP((r)) and is the
      clinically relevant threshold used to classify serum samples from allergic
      individuals.

PMID- 24028906
TI  - Additive effects of childhood abuse and cannabis abuse on clinical expressions of
      bipolar disorders.
AB  - BACKGROUND: Previous studies of bipolar disorders indicate that childhood abuse
      and substance abuse are associated with the disorder. Whether both influence the
      clinical picture, or if one is mediating the association of the other, has not
      previously been investigated. METHOD: A total of 587 patients with bipolar
      disorders were recruited from Norway and France. A history of childhood abuse was
      obtained using the Childhood Trauma Questionnaire. Diagnosis and clinical
      variables, including substance abuse, were based on structured clinical
      interviews (Structured Clinical Interview for DSM-IV Axis I disorders or French
      version of the Diagnostic Interview for Genetic Studies). RESULTS: Cannabis abuse
      was significantly associated with childhood abuse, specifically emotional and
      sexual abuse (chi 2 = 8.63, p = 0.003 and chi 2 = 7.55, p = 0.006, respectively).
      Cannabis abuse was significantly associated with earlier onset of the illness (z
      = -4.17, p < 0.001), lifetime history of at least one suicide attempt (chi 2 =
      11.16, p = 0.001) and a trend for rapid cycling (chi 2 = 3.45, p = 0.06). Alcohol
      dependence was associated with suicide attempt (chi 2 = 10.28, p = 0.001), but
      not with age at onset or rapid cycling. After correcting for possible confounders
      and multiple testing, a trend was observed for an interaction between cannabis
      abuse and childhood abuse and suicide attempt (logistic regression: r 2 = 0.06, p
      = 0.039). Significant additive effects were also observed between cannabis abuse
      and childhood abuse on earlier age at onset (p < 0.001), increased rapid cycling
      and suicide attempt (logistic regression: r 2 = 0.03-0.04, p < 0.001). No
      mediation effects were observed; childhood abuse and cannabis abuse were
      independently associated with the disorder. CONCLUSIONS: Our study is the first
      to demonstrate significant additive effects, but no mediation effects, between
      childhood abuse and cannabis abuse on increased clinical expressions of bipolar
      disorders.

PMID- 24028907
TI  - Livedoid vasculopathy: an in-depth analysis using a modified Delphi approach.
AB  - Livedoid vasculopathy (LV) is a noninflammatory thrombotic condition presenting
      in a primary idiopathic or secondary subtype associated with abnormal coagulation
      factors. Different from atrophie blanche (AB), which is a clinical manifestation
      of certain scars, LV may have AB in combination with recurrent livedo reticularis
      with chronic and painful skin ulcers particularly around the ankle region, and at
      the back of the feet. Histology is characterized by segmental hyalinizing changes
      at the subintimal region of small dermal vessels with thrombotic occlusions. LV
      skin ulcers resolve with stellate, porcelain-white scars that need to be
      distinguished from similar changes seen with venous insufficiency. "Atrophie
      blanche" was originally used synonymously with "livedoid vasculopathy." AB
      describes spontaneously occurring porcelain-white skin areas with red dots that
      typically occur in the context of skin changes attributed to chronic venous
      insufficiency. The 2 forms of AB--(1) the LV-AB complex and (2) AB in the context
      of chronic venous insufficiency--are unrelated and require separate diagnostic
      and therapeutic approaches. Using a modified Delphi method, we have developed an
      international consensus document on the diagnosis and management of LV.
      Individual sections of this document provide advice on diagnosis and management
      of LV.

PMID- 24028908
TI  - Low-dose brain computer tomography sensitivity: a comparative study with a
      conventional technique.
AB  - A comparative study between brain conventional computed tomography (CT)
      examinations and low-dose examinations was performed. The aim of the work was to
      show if a low-dose technique can be used instead of a standard one. Forty
      patients with 51 brain lesions were studied with both techniques. The low-dose
      technique was optimized with mAs reduction to obtain a 25% dose reduction
      compared to standard acquisitions. Even if images have a poor signal-to-noise
      ratio, the low-dose technique visualized all the lesions disclosed by
      conventional examination except three chronic vascular lacunar infarcts. In
      conclusion, the low-dose technique can be adopted instead conventional CT scans
      in selected cases. 

PMID- 24028909
TI  - Diagnostic Ability of Fluid-Attenuated Inversion Recovery MR Imaging to Detect
      Remnant or Recurrent Meningiomas after Resection.
AB  - It has been suggested that a difference in signal intensity (SI) between the
      resection cavity and normal cerebrospinal fluid (CSF) on fluid-attenuated
      inversion recovery (FLAIR) magnetic resonance imaging (MRI) in partially resected
      gliomas indicates subsequent or coincident tumor progression. We considered that
      this would hold true for resected meningiomas as well. Hence, we aimed to assess
      whether or not such a difference in the SI during the follow-up evaluation helps
      predict residual or recurrent tumor in resected meningiomas. We evaluated 63
      patients with resected meningiomas. The SI within the resection cavity observed
      on FLAIR images was qualitatively and quantitatively assessed during follow-up.
      Qualitative analysis comprised visual comparison of the SI in the resection
      cavity with that of normal CSF by neuroradiologists. The SI in the resection
      cavity was quantitatively assessed by region of interest (ROI) analysis and
      normalized against the background noise and CSF SI. Normalized SI recorded during
      follow-up was compared with that recorded immediately after resection. Tumor
      progression was defined as a 20% or greater increase in the diameter of the
      longest residual or recurrent meningioma (Response Evaluation Criteria in Solid
      Tumors). The sensitivity and specificity of the elevated SI in the resection
      cavity for indicating residual or recurrent tumor were calculated. Qualitative
      analysis by FLAIR MRI showed that patients with remnant tumor following surgery
      had a prolonged SI increase in the resection cavity. Further, SI increase could
      not always be observed before recurrence, and both SI increase and regrowth
      remnant/recurrence could be detected in the same MRI examination. In resected
      meningiomas, leakage of tumor elements into the resection cavity, presumably
      tumor cells, manifests as an SI increase on FLAIR images and indicates residual
      or recurrent tumor. However, unlike the previous reports on partially resected
      gliomas, we concluded that the SI change does not always precede tumor
      progression or recurrence. 

PMID- 24028910
TI  - Radiological findings in gliosarcoma. A single institution experience.
AB  - Gliosarcomas are rare tumors with a poor prognosis composed of intermingled
      malignant glial and sarcoma elements with an estimated incidence of 1.8-8.0% of
      all malignant astrocytic neoplasms. We aimed to review the imaging findings in
      eight patients with gliosarcoma who were treated in our center between 2002 and
      2010. The diagnosis was confirmed by morphological and immunohistochemical
      stains. This study, to the best of our knowledge, is the largest describing the
      imaging manifestations of this tumor. Although our study revealed no unique
      radiological features for gliosarcoma, it is important to note that they all
      demonstrated either dural or ependymal involvement or both. Calcification,
      hemorrhage or cystic components are described with a tendency for a ring
      enhancement pattern. Interestingly pre-existing benign looking lesions and
      associated remotely located small meningiomas are also described. 

PMID- 24028911
TI  - Xanthogranuloma of the sellar region. A case report.
AB  - Xanthogranuloma of the sellar region is a rare tumor. We describe a 41-year-old
      man complaining of several years of headache and passing out. Physical
      examination revealed absence of pubic and axillary hair while laboratory analysis
      showed panhypopituitarism. Magnetic resonance imaging showed a partially
      calcified slightly enhancing intrasellar mass with suprasellar extension which
      was slightly hyperintense on T1 images and hypointense on T2 images. Complete
      resection of the tumor mass using trans-sphenoidal approach was performed. On
      histopathologic analysis, there was a combination of fibrous scar tissue with
      chronic inflammation, highlighted by CD45 immunostaining, and extensively
      calcified necrotic debris, including cholesterol crystals consistent with a
      diagnosis of xanthogranuloma. 

PMID- 24028912
TI  - Cervical chordoma. A case report and differential diagnosis.
AB  - Chordomas are rare and aggressive tumors derived from notochordal remnants,
      usually arising in the axial skeleton. The most frequently reported anatomic
      distribution of chordoma is 50% sacral, 35% spheno-occipital and 15% spinal. We
      describe the case of an elderly lady presenting with progressive dysphagia,
      headache and neck pain. We found an expansile mass extending from C1 to C3. While
      running the diagnostic plan we considered a variety of lesions possibly involving
      the cervical spine. Biopsy revealed the mass was a chordoma. 

PMID- 24028913
TI  - Primary Skull Osteosarcoma: MDCT Evaluation and Histopathological Correlation in
      Two Cases.
AB  - Osteosarcomas are typically long bone tumors and rarely affect the skull, with
      most articles reporting single cases. As elsewhere in the body, these lesions may
      be classified as primary or secondary, chiefly post-Paget and post-radiation
      therapy. We describe two cases of primary osteosarcoma of skull one presenting
      with cerebellar symptoms and another with giant skull swelling. Complete
      evaluation with 64 slice CT and histopathological correlation was carried out. 

PMID- 24028914
TI  - Brain fat embolism. A report of two cases and a brief review of neuroimaging
      findings.
AB  - Fat embolism syndrome [FES] is an uncommon but serious complication of traumatic
      injures, which can follow a wide range of other surgical and medical conditions
      and can manifest with a collection of respiratory, hematological, neurological
      and cutaneous symptoms. FES should be suspected in all cases of traumatic injures
      with altered mental status following a period of normal neurological function,
      especially after orthopedic fixation of long bone fractures. Neurological
      symptoms must not be related to the initial trauma. The objective of this study
      was to describe the characteristics of FES and to correlate the neuroradiological
      findings with the clinical symptoms and the outcome of two cases of cerebral FES
      which occurred in two young men after bone fractures of the extremities without
      cranial traumatism. Both patients were studied by brain computed tomography (CT)
      and by brain magnetic resonance (MR). While Cerebral CT was inadequate to the
      diagnosis, Cerebral MR, performed 48 hours after injury, showed several focal
      areas of pathological signal in the white matter of the subcortical,
      periventricular and centrum semiovale regions, as well as in the basal ganglia
      and cerebellum. The neuroradiological findings of the two patients were compared
      with their clinical symptoms and outcome. The patient with the worst prognosis
      showed more lesions on MR and a restricted diffusion on DWI-MR, due to cytotoxic
      edema, whereas the patient with the better outcome showed lesions due to
      vasogenetic edema without any restricted diffusion. Cerebral MR and DW-MR are
      sensitive indicators for the early diagnosis of FES and can give a vast amount of
      information on the prognosis and future outcome. 

PMID- 24028915
TI  - An uncommon manifestation of a common tropical disease: disseminated
      cysticercosis.
AB  - Disseminated cysticercosis is a rare form of cysticercosis in which the
      cysticerci spread throughout the body. We describe the case of a seven-year-old
      child with disseminated cysticercosis. He presented with a one month history of
      swelling of the whole body, unable to walk for one month and swelling of both
      eyes for 20 days. After extensive investigation from superficial musculoskeletal
      ultrasound B-scan of eye, brain computed tomography, brain magnetic resonance
      imaging (MRI), whole body MRI and pathologic biopsy, the child was diagnosed as
      having cysticercosis involving the brain, retina and skeletal muscles throughout
      the whole body. 

PMID- 24028916
TI  - Stable neurocutaneous melanosis in a ten-year-old boy with controlled partial
      complex seizures. A case report.
AB  - Neurocutaneous melanosis (NCM) is a rare neuroectodermal dysplasia that includes
      both central nervous system (CNS) and integumentary melanocytic abnormalities.
      NCM can present with varied clinical and imaging findings, classically presenting
      with large melanocytic nevi involving the posterior axial trunk region. We
      describe a case with predominant small non-scalp and non posterior axial-trunk
      nevi, which nevertheless demonstrated typical CNS imaging findings. Our case
      clinically presented with epilepsy that was controlled by medical treatment. The
      patient also demonstrated motor developmental delay, and an otherwise stable
      course. 

PMID- 24028917
TI  - Selective occipital artery sonography for dural arteriovenous fistulas. A case
      report.
AB  - Carotid duplex sonography is a useful method for evaluation of dural
      arteriovenous fistulas. The resistance index of the external carotid artery has
      been reported to correlate with the efficacy of treatment and recurrence or
      aggravation of dural arteriovenous fistulas. Herein, we describe a case of dural
      arteriovenous fistulas mainly supplied by the occipital artery and show that the
      resistance index of the occipital artery was more sensitive than that of the
      external carotid artery. To the best of our knowledge, this is the first report
      to describe the feasibility of occipital artery detection by carotid duplex
      sonography and clinical application of the resistance index of the occipital
      artery for dural arteriovenous fistulas. 

PMID- 24028918
TI  - Spinal subarachnoid hemorrhage mimicking an acute abdomen.
AB  - A 39-year-old woman with a history of systemic lupus erythematosum developed an
      acute abdomen. An intestinal ischemia was suspected and an exploratory laparotomy
      was performed. No abnormalities were found during surgery and five days later the
      patient was transferred to our institution. On admission, the patient presented a
      distended abdomen and paraparesis. The spinal tap showed hemorrhagic CSF and the
      MRI a subacute subarachnoid hemorrhage (SAH) of the dorsal-lumbar spine. Two days
      later, the patient suffered an episode of sudden headache. The CT scan revealed
      an acute SAH at the posterior fossa and digital subtraction angiography a
      dissection of the right V4 segment. Spinal subarachnoid hemorrhage is a rare
      syndrome particularly when associated with dissecting aneurysms of the
      intracranial segment of the vertebral artery. SSAH should be considered early in
      the differential diagnosis of any case with sudden back or abdominal pain of
      unknown etiology, even in the absence of neurological deficits. 

PMID- 24028919
TI  - Early encephalic toxicity after inadvertent intrathecal injection of low osmolar
      contrast medium.
AB  - Only nonionic contrast media are allowed for intrathecal use because of their
      lower neurotoxicity. In case of inadvertent intrathecal administration of an
      ionic contrast medium, the typical following syndrome is called ascending tonic
      clonic seizure syndrome. We describe the case of a 61-year-old woman with low
      back pain who underwent myelography. Ioxaglate, a water-soluble ionic low osmolar
      contrast medium was accidentally injected intrathecally. She first presented
      encephalic signs of neurotoxicity, followed by opisthotonic spasms and
      respiratory distress. In our case, ioxaglate is a low osmolar agent, leading to
      early encephalic toxicity (preceding medullary signs), because of its cephalic
      migration. The patient was successfully treated by sedation, anticonvulsant
      therapy and fluid hydration. Intrathecal administration of an ionic contrast
      medium is clearly contraindicated. In case of inadvertent injection of a low
      osmolar product, encephalic signs are seen first. 

PMID- 24028920
TI  - Spontaneous ruptured cavernous aneurysm treated by stenting and embolization in a
      young patient. A case report and literature review.
AB  - We describe a case of endovascular management of a ruptured aneurysm of the
      intracavernous portion of the left internal carotid artery with sphenoid
      extension. The exclusive use of coils to embolize the aneurysm in acute and young
      patients offers the advantage of avoiding both pre-implant antiplatelet therapy
      and long-term anticoagulant therapy required after stent or vascular plug
      placement, but it is complicated by the non-negligible risk of recurrence.
      Indeed, the only secure method to treat ruptured aneurysms of the intracavernous
      portion of the internal carotid artery is to use coils in the first stage to stop
      the haemorrhage without antiplatelet therapy and to use stents in the second
      narrow stage to prevent revascularization. 

PMID- 24028921
TI  - Coils and onyx embolization of traumatic carotid-cavernous fistula caused by an
      intradural internal carotid artery pseudoaneurysm.
AB  - A rare case of traumatic carotid-cavernous fistula caused by an intradural
      internal carotid artery pseudoaneurysm arising from the intradural internal
      carotid artery is described. The presentation was similar to that of carotid
      cavernous fistulae, with ocular pain, chemosis and proptosis being the common
      symptoms. The patient was successfully treated by transarterial coil and Onyx-34
      embolization. A 40-year-old man presented with severe injury, including multiple
      fractures of ribs, clavicle scapula and blind left eye. He gradually recovered
      and was discharged after intensive treatment in a local hospital. But about 70
      days after discharge, his left eye became gradually chemotic and he felt a
      pulsatile bruit in his left ear. A CT scan and DSA confirmed a large intradural
      pseudoaneurysm and the associated carotid-cavernous fistula. Angiography revealed
      a fistula between the intradural aneurysm and the cavernous sinus. The origin of
      the aneurysm was above the posterior communicating artery. The aneurysm was
      successfully obliterated with detachable coils and Onyx-34 with the protection of
      a Hyperglide balloon. Subsequent studies demonstrated no flow through the fistula
      and good opacification of the ipsilateral internal cerebral artery
      system.Intradural pseudoaneurysm associated with carotid-cavernous fistula is a
      rare sequel of trauma. It may be treated successfully with the use of
      transarterial coil and Onyx embolization. 

PMID- 24028922
TI  - Ipsilateral stroke with uncrossed pyramidal tracts and underlying right internal
      carotid artery stenosis treated with percutaneous transluminal angioplasty and
      stenting. A rare case report and review of the literature.
AB  - We present a unique case of ipsilateral stroke in a 55-year-old right-handed
      hypertensive man with proven uncrossed pyramidal tract demonstrated by
      tractography. Diffusion-weighted imaging disclosed small acute ischemic infarcts
      in the right corona radiata with MR angiography showing narrowing of the right
      internal carotid artery. Significant carotid stenosis of right internal carotid
      artery (ICA) was detected on digital subtraction angiography as the underlying
      cause and subsequently treated with percutananeous transluminal angioplasty and
      stenting with good outcome. The presence of uncrossed pyramidal tract was
      confirmed by diffusion tensor imaging tractography. To our knowledge there are
      few reports of ipsilateral stroke with proven uncrossed pyramidal tracts
      described in the literature. This is the first documented report of ipsilateral
      stroke with uncrossed fibre tracts due to underlying critical stenosis of the ICA
      treated successfully with a good recovery. 

PMID- 24028923
TI  - Passing the thrombus in endovascular treatment of acute ischemic stroke: do we
      penetrate the thrombus?
AB  - Mechanical thrombectomy is increasingly applied during the treatment of acute
      stroke. Various devices have been advocated with different sites of force effect
      at the thrombus. The purpose of this study was to evaluate the angiographic route
      of passing systematically and therefore to assess the site of deployment of
      mechanical devices in correlation to the thrombus in interventional stroke
      treatment. Twenty-one consecutive patients with endovascular treatment for acute
      ischemic stroke with 26 passing procedures were evaluated prospectively.
      Occlusion site was the M1-segment in 17 cases (65.4%), ICA termination in five
      cases (19.2%), M2-segment in two cases (7.7%), the A2-segment in one case (3.8%)
      and basilar artery in one case (3.8%). On angiographic images the microwire and
      microcatheter passage was evaluated by illustrating the entry point and course
      across the occlusion site in relation to the thrombus in different projections
      and in correlation to the recanalisation result. Results were correlated to the
      origin of the thrombi according to the TOAST criteria. In all cases the point of
      entry to the occlusion site was delineated laterally to the thrombus in at least
      one projection. The course of the wire across the occluded segment in relation to
      the thrombus was found to be laterally in 22 procedures (84.6%). In the majority
      of M1-occlusions (12/17, 70.6%) the passage was found in the cranial aspect of
      the thrombus. In four procedures (15.4%) angiograms in different projections did
      not unequivocally confirm a passage laterally to the thrombus. The route of
      passing the thrombus was independent of thrombus origin according to the TOAST
      criteria. In the majority of cases the complete route of passing the occlusion
      site was visualized angiographically. Entrance of the microwire and microcatheter
      at proximal surface of the thrombus takes place laterally to the thrombus and
      accordingly the passage takes place between the thrombus and the vessel wall
      independent of thrombus origin. A penetration of the thrombus was not observed.
      This route of passing has implications on deployment and transmission of force in
      relation to the thrombus in mechanical approaches and consequently on the
      development of retrieval devices. 

PMID- 24028924
TI  - Spontaneous recanalization of the occluded internal carotid artery. A report of
      two cases.
AB  - Spontaneous recanalization of the occluded internal carotid artery (ICA) is more
      frequent than is generally believed. The timing of spontaneous recanalization
      remains unclear but it may occur as either an early or a late event. The aim of
      this case report is to emphasize the importance of spontaneous recanalization and
      its consequences. From September 2008 to November 2010 we prospectively followed
      patients with old ICA occlusion. The diagnoses of an occlusion were based on
      duplex scan findings and were confirmed by CT angiography and digital subtraction
      angiography (DSA). ICA occlusions secondary to dissection, inflammatory process,
      like fibromuscular dysplasia, previous stenting or endarterectomy and trauma,
      were excluded from the study. All patients had a scheduled carotid duplex scan
      every six months. Overall 65 patients were enrolled. Two patients showed evidence
      of spontaneous recanalization. A 55-year-old man with a known history of
      transient ischemic attack had occlusion in the left side ICA. He presented with
      another TIA eight months later. Investigations showed evidence of rcanalization
      of occluded ICA. This artery underwent uneventful stenting. In another patient
      recanalization was heralded by global aphasia and right side hemiplegia. He was a
      70-year-old man with a history of recurrent TIA. Carotid duplex scan and DSA
      showed recanalization of the occluded left ICA accompanied by occlusion of the
      ipsilateral middle cerebral artery. He remained profoundly disabled with severe
      neurological deficits. In conclusion, spontaneous recanalization of the occluded
      internal carotid artery is a potentially complicated event that may lead to
      severe neurological disability. 

PMID- 24028926
TI  - Self-catalyzed MBE grown GaAs/GaAs(x)Sb(1-x) core-shell nanowires in ZB and WZ
      crystal structures.
AB  - We have investigated the growth of self-catalyzed GaAs/GaAs(x)Sb(1-x) core-shell
      nanowires directly on Si(111) substrates by molecular beam epitaxy. The
      compositions of the GaAs(x)Sb(1-x) shells are tuned in a wide range where the Sb
      content is varied from 10 to ~70%, covering the miscibility gap. In addition, the
      GaAs(x)Sb(1-x) shells are grown on both zinc blende (ZB) and wurtzite (WZ)
      crystal structures. Morphological and structural characterizations of the grown
      nanowires indicate successful transfer of the GaAs core crystal structure to the
      GaAs(x)Sb(1-x) shells for both ZB and WZ nanowires, with slower shell growth rate
      on the WZ segments.

PMID- 24028925
TI  - The significance of alpha-synuclein, amyloid-beta and tau pathologies in
      Parkinson's disease progression and related dementia.
AB  - BACKGROUND: Dementia is one of the milestones of advanced Parkinson's disease
      (PD), with its neuropathological substrate still being a matter of debate,
      particularly regarding its potential mechanistic implications. OBJECTIVE: The aim
      of this study was to review the relative importance of Lewy-related alpha
      synuclein and Alzheimer's tau and amyloid-beta (Abeta) pathologies in disease
      progression and dementia in PD. METHODS: We reviewed studies conducted at the
      Queen Square Brain Bank, Institute of Neurology, University College London, using
      large PD cohorts. RESULTS: Cortical Lewy- and Alzheimer-type pathologies are
      associated with milestones of poorer prognosis and with non-tremor predominance,
      which have been, in turn, linked to dementia. The combination of these
      pathologies is the most robust neuropathological substrate of PD-related
      dementia, with cortical Abeta burden determining a faster progression to
      dementia. CONCLUSION: The shared relevance of these pathologies in PD progression
      and dementia is in line with experimental data suggesting synergism between alpha
      synuclein, tau and Abeta and with studies testing these proteins as disease
      biomarkers, hence favouring the eventual testing of therapeutic strategies
      targeting these proteins in PD.

PMID- 24028927
TI  - Parkinsonian features in a case of pellagra: a historical report.
AB  - Pellagra is a complex systemic disease resulting from inadequate dietary intake
      of coenzyme precursors nicotinamide and tryptophan. Improved nutritional habits
      in most developed economies have led to a decrease in clinicians' and
      researchers' attention to this condition and its pathophysiological bases,
      although new cases of pellagra have recently been identified in association with
      alcohol abuse and HIV infection in Western countries. Pellagra is characterized
      by a complex clinical picture, which can include neuropsychiatric symptoms and
      Parkinsonian features. Interestingly, pellagra and Parkinson's disease could
      share some basic pathophysiological mechanisms at the level of nicotinamide
      metabolism, resulting in mitochondrial dysfunction and alterations in
      dopaminergic pathways. Both neuropsychiatric and motor symptoms were mentioned in
      historical reports of pellagra cohorts. Here we present the English translation
      of the first detailed description of an original case of pellagra with
      Parkinsonian features, documented in a clinical note by Dr Giuseppe Paravicini
      one century ago. 

PMID- 24028928
TI  - Postgraduate education in internal medicine in Europe.
AB  - BACKGROUND: Limited information exists on the framework and content of
      postgraduate education in internal medicine in Europe. This report describes the
      results of a survey of postgraduate training in internal medicine in the European
      countries. METHODS: Two online questionnaire-based surveys were carried out by
      the European Board of Internal Medicine, one on the practice of internists and
      the other on postgraduate training in internal medicine. The national internal
      medicine societies of all 30 member countries of the European Federation of
      Internal Medicine were invited to participate. The responses were reviewed by
      internal medicine residents from the respective countries and summaries of the
      data were sent to the national societies for approval. Descriptive analysis of
      the data on postgraduate training in internal medicine was performed. RESULTS:
      Twenty-seven countries (90%) completed the questionnaire and approved their
      datasets. The length of training ranged from four to six years and was commonly
      five years. The majority of countries offered training in internal medicine and a
      subspecialty. A common trunk of internal medicine was frequently a component of
      subspecialty training programmes. Hospital inpatient service was the predominant
      setting used for training. A final certifying examination was in place in 14
      countries. CONCLUSION: Although some similarities exists, there appear to be
      significant differences in the organisation, content and governance of
      postgraduate training in internal medicine between the European countries. Our
      findings will prove invaluable for harmonisation of training and qualification in
      internal medicine in Europe.

PMID- 24028929
TI  - The practice of internal medicine in Europe: organisation, clinical conditions
      and procedures.
AB  - BACKGROUND: Current information on the role of internists in the European
      countries is scarce. This report describes the results of a survey of the
      practice of internists in Europe. METHODS: Two online questionnaire-based surveys
      were carried out by the European Board of Internal Medicine, one on the practice
      of internists and the other on postgraduate training in internal medicine. The
      national internal medicine societies of all 30 member countries of the European
      Federation of Internal Medicine were invited to participate. The responses were
      reviewed by internal medicine trainees from the respective countries and
      summaries of the data were sent to the national societies for approval.
      Descriptive analysis of the data on the practice of internists was carried out.
      RESULTS: Twenty-seven countries (90%) completed the questionnaire and approved
      their datasets. In 8 European countries, most internists practised internal
      medicine alone and in 7 countries at least half of physicians practised internal
      medicine together with a subspecialty. Internal medicine was considered a
      hospital-based specialty in most countries. The majority of selected presenting
      problems and diagnoses were rated as commonly encountered in all countries. More
      variability between countries was observed in the performance of diagnostic and
      therapeutic procedures. CONCLUSION: Many similarities exist in the practice of
      internal medicine between the European countries, while some differences are
      present that likely reflect the variable impact of subspecialisation. The results
      of the survey should prove valuable for the definition of specific competencies
      and development of a common curriculum for internal medicine at the European
      level.

PMID- 24028930
TI  - Extrapulmonary tuberculosis: 7 year-experience of a tertiary center in Istanbul.
AB  - BACKGROUND: Although a decreasing trend of tuberculosis (TB) was reported in
      Turkey, higher proportion of extrapulmonary tuberculosis (EPT) was revealed.
      MATERIAL AND METHODS: In this retrospective study, clinical and laboratory data
      of 141 EPT patients were evaluated for a seven-year period by using descriptive
      statistics, and parametric and non-parametric tests where appropriate. RESULTS:
      The most frequent types of EPT were meningeal TB (23%) and TB lymphadenitis
      (21%), respectively. Other types of EPT were skeletal, miliary, peritoneal,
      abscess, genitourinarial, cutaneous and gastrointestinal involvement which ranged
      between 18% and 1%. Mean age was 42 and female/male ratio was almost equal. All
      patients were born in Turkey. Although all of them were permanent residents of
      Istanbul, 73% of the patients came from East and Southeast Region of Turkey. For
      the patients, being older than 40 years old (p<0.01), having miliary TB (p<0.05)
      and high CRP levels (p<0.05) were found to be associated with mortality.
      CONCLUSIONS: EPT still remains as a significant morbidity and mortality reason in
      lower income populations and developing countries. In our study, although all
      patients were residents of Istanbul approximately two thirds of them have
      migrated from East and Southeast parts of the country. The relatively high
      prevalence of tuberculosis cases in Istanbul may be due to the permanent
      migration from other parts of the country. Early diagnosis and initiation of
      appropriate treatment are the keys for reducing morbidity and mortality in
      patients with EPT, particularly in the cases of older ages.

PMID- 24028931
TI  - Cerebral arterial infarction in inflammatory bowel diseases.
AB  - It has been estimated that up to 10% of hypercoagulable state manifestations in
      patients with inflammatory bowel disease (IBD) are ischemic strokes. The
      literature search through MEDLINE and EMBASE highlighted 33 case reports of IBD
      patients complicated with cerebral arterial infarction during the course of their
      disease. Most of these patients presented with either left or right sided
      hemiparesis on admission, while the most common site of arterial infarction was
      either the right or the left middle cerebral artery. Thrombocytosis and anemia
      were the most commonly observed potential risk factors for stroke in the
      laboratory analysis. Other coagulation abnormalities, hereditary thrombotic
      mutations, hyperhomocysteinemia, hyperlipidemia, structural cardiac
      abnormalities, endocarditis and cerebral artery vasculitis have also been
      reported in some of the cases that were reviewed. Even though many of these
      findings are commonly observed in IBD patients, literature data is still
      controversial about their causal relationship to ischemic stroke. Similarly,
      there is also lack of steady evidence and official guidelines for stroke
      management in both children and adults with IBD comorbidity. Finally, an
      algorithm based on both the American Heart Association and European Stroke
      Organization guidelines for stroke management and prevention in the general
      population, is presented as a reference point for the treatment of IBD patients
      who are complicated by an ischemic cerebral event. 

PMID- 24028932
TI  - Strong cation exchange chiral stationary phase--a comparative study in high
      performance liquid chromatography and subcritical fluid chromatography.
AB  - The performance of a strong cation exchange-type (SCX) chiral stationary phase
      (CSP) was evaluated with subcritical fluid chromatography (subFC) and high
      performance liquid chromatography (HPLC). The chromatographic conditions in subFC
      were optimized by changing the amount of polar organic modifier, concentration of
      a basic additive in the modifier, system pressure and temperature. In this way
      the concentration of in situ formed transient ionic species could be varied. The
      gradual change of the concentration of the transient buffer, i.e. gradient
      elution conditions in subFC, was found beneficial for separation of a mixture of
      racemic compounds. The strength and amount of the in situ formed buffer was
      estimated on the basis of comparative experiments in subSFC and HPLC. 

PMID- 24028933
TI  - Quantification of ethylenediamine-N,N'-bis(hydroxysulfophenylacetic) acid
      regioisomers and structural characterisation of its related polycondensation
      products by porous graphitic carbon high-performance liquid chromatography
      coupled to electrospray tandem mass spectrometry.
AB  - Among the commercial ethylenediamine-N,N'-bis(2-hydroxy)phenylacetic
      acid/iron(III) derivatives, ethylenediamine-N,N'-bis(2-hydroxy-5
      sulphophenylacetic) acid/iron(III) (EDDHSA/Fe) represents one of the promising
      chelates for the treatment of chlorotic plants. Industrial synthesis of EDDHSA/Fe
      leads to relevant amounts of o,o-EDDHSA condensation products (o,o-EDDHSAcps) and
      other secondary products that might have important relevance from the agronomic
      point of view. However, their chemical structures have remained unknown to date.
      Analysis of iron complexes by ion-pair reversed-phase chromatography, coupled
      with electrospray tandem mass spectrometry revealed the presence of the meso-o,o
      EDDHSA/Fe, rac-o,o-EDDHSA/Fe, o,p-EDDHSA/Fe regioisomers, the hydroxyl derivative
      of o,o-EDDHSA/Fe, and the three main EDDHSA condensation products chelating the
      iron(III) (EDDHSAcps/nFe). However, the chromatographic peaks of EDDHSAcps/Fe are
      not well resolved due to the large numbers of stereoisomers and the poor
      efficiency of the ion-pair reversed-phase separation method. An alternative
      chromatographic method is based on porous graphitic carbon (PGC) separation after
      pre-column decomplexation of the chelates with trifluoracetic acid, which was
      developed to allow detection of EDDHSA stereo/regioisomers, EDDHSAcps, and low
      molecular-weight by-products. This extensive PGC-HPLC-ESI-MS/MS investigation
      provides quantitative determination of meso-o,o-EDDHSA, rac-o,o-EDDHSA and o,p
      EDDHSA, in addition to characterisation of EDDHSAcps and the low-molecular-weight
      by-products. PGC separation coupled to a triple quadrupole ESI-MS detector
      allowed characterisation of free ligands using collision-induced dissociation
      experiments in positive and negative ionisation mode, providing comparative
      evaluation of EDDHSAcps in three commercial samples. For detection, the PGC-HPLC
      ESI-MS/MS is the best method according to the limit of quantification and limit
      of detection (picomolar and sub-picomolar detection, respectively) for
      determination of meso-EDDHSA and rac-o,o-EDDHSA. Synthesis, purification and
      quantification of o,o-EDDHSA and o,p-EDDHSA by (1)H-nuclear magnetic resonance
      are also reported. 

PMID- 24028934
TI  - Detection and quantification of ionophore antibiotics in runoff, soil and poultry
      litter.
AB  - Ionophore antibiotics (IPAs) are widely used as coccidiostats in poultry and
      other livestock industries to promote growth and prevent infections. Because most
      of the ingested IPAs are excreted in poultry litter, which is primarily applied
      as grassland fertilizer, a significant amount of IPAs can be released into the
      litter-soil-water environment. A robust analytical method has been developed to
      quantify IPAs (monensin (MON), salinomycin (SAL) and narasin (NAR)) in complex
      environmental compartments including surface runoff, soil and poultry litter,
      with success to minimize matrix interference. The method for water samples
      involves solid-phase extraction (SPE) followed by liquid-liquid extraction (LLE)
      post-clean up steps. The method for solid samples involves bi-solvent LLE. IPAs
      were detected by HPLC-MS, with optimized parameters to achieve the highest
      sensitivity. Nigericin (NIG), an IPA not used in livestock industry, is
      successfully applied and validated as a surrogate standard. The method recoveries
      were at 92-95% and 81-85% in runoff samples from unfertilized and litter
      fertilized fields, respectively. For solids, the method recoveries were at 93-99%
      in soils, and 79-83% in poultry litter samples. SAL was detected at up to 22mg/kg
      and MON and NAR at up to 4mg/kg in broiler litter from different farms. Up to
      183MUg/kg of MON was detected in litter-fertilized soils. All three IPAs were
      detected in the rainfall runoff from litter-fertilized lands at concentrations up
      to 9MUg/L. 

PMID- 24028935
TI  - Human C-reactive protein induces endothelial dysfunction in biobreeding diabetic
      rats.
AB  - OBJECTIVE: C-reactive protein (CRP) levels in diabetes predict cardiovascular
      events. Also, human CRP (hCRP) exacerbated the proinflammatory, pro-oxidant and
      procoagulant states in a spontaneous model of type 1 diabetes mellitus (T1DM),
      the biobreeding (BB) rat. Since there is a paucity of data examining the role of
      CRP on endothelial dysfunction in animal models of diabetes, we tested this
      hypothesis in the diabetic BB rat. METHODS: Diabetic BB rats (n = 4 per group)
      were injected with human serum albumin (HSA) or hCRP [hCRP = 20 mg/kg body
      weight; intraperitoneal (IP)] for three consecutive days. The rats were
      euthanized on day 4. Biomarkers that were assayed included endothelin-1 (ET-1),
      soluble intracellular adhesion molecule-1 (sICAM-1), Von Willebrand factor (vWF)
      and 6-keto prostaglandin F1-alpha (6-keto PGF1-alpha) in plasma. RESULTS: hCRP
      administration resulted in a significant increase in plasma levels. Furthermore,
      hCRP-treated rats had significantly increased circulating levels of ET-1 (1.12 +/
      0.6 pg/mL versus 0.4 +/- 0.21 pg/mL), vWF (45 +/- 2.4 ng/mL versus 34 +/- 7
      ng/mL) and sICAM-1 (41 +/- 3 ng/mL versus 34 +/- 3.4 ng/mL) compared to HSA
      treated rats (p < 0.05). There was no significant effect on 6-keto PGF1-alpha
      levels. CONCLUSION: Hence, in this preliminary report, we make the novel
      observation that hCRP induces endothelial dysfunction in a spontaneous model of
      T1DM, and this could have implications for the vascular complications in
      diabetics.

PMID- 24028936
TI  - The role of social participation in municipal-level health systems: the case of
      Palencia, Guatemala.
AB  - BACKGROUND: Social participation has been recognized as an important public
      health policy since the declaration of Alma-Ata presented it as one of the
      pillars of primary health care in 1978. Since then, there have been many
      adaptations to the original policy but participation in health is still seen as a
      means to make the health system more responsive to local health needs and as a
      way to bring the health sector and the community closer together. OBJECTIVE: To
      explore the role that social participation has in a municipal-level health system
      in Guatemala in order to inform future policies and programs. DESIGN: Documentary
      analysis was used to study the context of participation in Guatemala. To do this,
      written records and accounts of Guatemalan history during the 20th century were
      reviewed. The fieldwork was carried out over 8 months and three field visits were
      conducted between early January of 2009 and late March of 2010. A total of 38 in
      depth interviews with regional health authorities, district health authorities,
      community representatives, and community health workers (CHWs) were conducted.
      Data were analyzed using thematic analysis. RESULTS: Guatemala's armed civil
      struggle was framed in the cold war and the fight against communism. Locally, the
      war was fed by the growing social, political, and ethnic inequalities that
      existed in the country. The process of reconstructing the country's social fabric
      started with the signing of the peace agreements of 1996, and continued with the
      passing of the 2002 legal framework designed to promote decentralization through
      social participation. Today, Guatemala is a post-war society that is trying to
      foster participation in a context full of challenges for the population and for
      the institutions that promote it. In the municipality of Palencia, there are
      three different spaces for participation in health: the municipal-level health
      commission, in community-level social development councils, and in the CHW
      program. Each of these spaces has participants with specific roles and processes.
      CONCLUSIONS: True participation and collaboration among can only be attained
      through the promotion and creation of meaningful partnerships between
      institutional stakeholders and community leaders, as well as with other
      stakeholders working at the community level. For this to happen, more structured
      support for the participation process in the form of clear policies, funding and
      capacity building is needed.

PMID- 24028937
TI  - Factors associated with attrition, mortality, and loss to follow up after
      antiretroviral therapy initiation: data from an HIV cohort study in India.
AB  - BACKGROUND: Studies from sub-Saharan Africa have shown high incidence of
      attrition due to mortality or loss to follow-up (LTFU) after initiating
      antiretroviral therapy (ART). India is the third largest country in the world in
      terms of HIV infected people, but predictors of attrition after ART initiation
      are not well known. DESIGN: We describe factors associated with attrition,
      mortality, and LTFU in 3,159 HIV infected patients who initiated ART between 1
      January 2007 and 4 November 2011 in an HIV cohort study in India. The study
      included 6,852 person-years with a mean follow-up of 2.17 years. RESULTS: After 5
      years of follow-up, the estimated cumulative incidence of attrition was 37.7%.
      There was no significant difference between attrition due to mortality and
      attrition due to LTFU. Having CD4 counts <100 cells/ul and being homeless
      [adjusted hazard ratio (aHR) 3.1, 95% confidence interval (CI) 2.6-3.8] were
      associated with a higher risk of attrition, and female gender (aHR 0.64, 95% CI
      0.6-0.8) was associated with a reduced risk of attrition. Living near a town (aHR
      0.82, 95% CI 0.7-0.999) was associated with a reduced risk of mortality. Being
      single (aHR 1.6, 95% CI 1.2-2.3), illiteracy (aHR 1.3, 95% CI 1.1-1.6), and age
      <25 years (aHR 1.3, 95% CI 1-1.8) were associated with an increased risk of LTFU.
      Although the cumulative incidence of attrition in patients diagnosed with
      tuberculosis after ART initiation was 47.4%, patients who started anti
      tuberculous treatment before ART had similar attrition to patients without
      tuberculosis (36 vs. 35.2%, P=0.19) after four years of follow-up. CONCLUSIONS:
      In this cohort study, the attrition was similar to the one found in sub-Saharan
      Africa. Earlier initiation of ART, improving the diagnosis of tuberculosis before
      initiating ART, and giving more support to those patients at higher risk of
      attrition could potentially reduce the mortality and LTFU after ART initiation.

PMID- 24028938
TI  - A multi-layered governance framework for incorporating social science insights
      into adapting to the health impacts of climate change.
AB  - BACKGROUND: Addressing climate change and its associated effects is a multi
      dimensional and ongoing challenge. This includes recognizing that climate change
      will affect the health and wellbeing of all populations over short and longer
      terms, albeit in varied ways and intensities. That recognition has drawn
      attention to the need to take adaptive actions to lessen adverse impacts over the
      next few decades from unavoidable climate change, particularly in developing
      country settings. A range of sectors is responsible for appropriate adaptive
      policies and measures to address the health risks of climate change, including
      health services, water and sanitation, trade, agriculture, disaster management,
      and development. OBJECTIVES: To broaden the framing of governance and decision
      making processes by using innovative methods and assessments to illustrate the
      multi-sectoral nature of health-related adaptation to climate change. This is a
      shift from sector-specific to multi-level systems encompassing sectors and
      actors, across temporal and spatial scales. DESIGN: A review and synthesis of the
      current knowledge in the areas of health and climate change adaptation governance
      and decision-making processes. RESULTS: A novel framework is presented that
      incorporates social science insights into the formulation and implementation of
      adaptation activities and policies to lessen the health risks posed by climate
      change. CONCLUSION: Clarification of the roles that different sectors,
      organizations, and individuals occupy in relation to the development of health
      related adaptation strategies will facilitate the inclusion of health and
      wellbeing within multi-sector adaptation policies, thereby strengthening the
      overall set of responses to minimize the adverse health effects of climate
      change.

PMID- 24028939
TI  - The alpha2-adrenoceptors mediating inhibition of the vasopressor sympathetic
      outflow in pithed rats: pharmacological correlation with alpha2A, alpha2B and
      alpha2C subtypes.
AB  - alpha2-Adrenoceptors were first described as presynaptic receptors inhibiting the
      release of various transmitters from neurons in the central and peripheral
      nervous systems. In vitro studies have confirmed that alpha2A, alpha2B and
      alpha2C subtypes inhibited noradrenaline release from postganglionic sympathetic
      neurons but no study has been reported their involvement in the vasopressor
      sympathetic outflow in vivo. Thus, this study analysed the subtype(s) involved in
      the inhibition produced by the alpha2-adrenoceptor agonist, B-HT 933, on the
      vasopressor sympathetic outflow. Male Wistar pithed rats were pre-treated with
      i.v. bolus injections of gallamine (25mg/kg) and desipramine (50 ug/kg) and
      prepared to stimulate the vasopressor sympathetic outflow (T7-T9) or to receive
      i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or exogenous
      noradrenaline produced, respectively, frequency-dependent and dose-dependent
      vasopressor responses. I.v. continuous infusion of B-HT 933 (30 MUg/kg min)
      failed to modify the vasopressor responses to exogenous noradrenaline and
      inhibited those induced by preganglionic stimulation of the vasopressor
      sympathetic outflow at all frequencies of stimulation (0.03-3 Hz). The sympatho
      inhibition elicited by B-HT 933 was: (i) unaffected by vehicles (1 ml/kg); (ii)
      partially antagonised by BRL44408 (300 MUg/kg; alpha2A), imiloxan (3000 MUg/kg;
      alpha2B) and/or JP-1302 (300 MUg/kg; alpha2C) given separately; and (iii)
      completely blocked by rauwolscine (300 MUg/kg) or the combination of BRL44408
      (300 MUg/kg)+imiloxan (3000 MUg/kg)+JP-1302 (300 MUg/kg). The above doses of
      antagonists did not modify per se the sympathetically-induced vasopressor
      responses. These results suggest that the vasopressor sympatho-inhibition to B-HT
      933 is primarily mediated by activation of alpha2A/2B/2C-adrenoceptors in pithed
      rats.

PMID- 24028940
TI  - Galangin inhibits proliferation of HepG2 cells by activating AMPK via increasing
      the AMP/TAN ratio in a LKB1-independent manner.
AB  - Galangin, a flavonol derived from Alpinia officinarum Hance and used as food
      additives in southern China, induces apoptosis and autophagy to suppress the
      proliferation of HepG2 cells. In this study, we demonstrated that galangin
      induced autophagy by increasing the ratio of AMP/TAN in HepG2 cells. It
      stimulated the phosphorylation of adenosine monophosphate-activated protein
      kinase (AMPK) and LKB1, but inhibited the phosphorylation of AKT and mTOR.
      Inhibition of AMPK activation suppressed the dephosphorylation of mTOR to block
      galangin-induced autophagy. AMPK activation by galangin appeared to be
      independent of the LKB1 signaling pathway because the down-regulation of LKB1 by
      its siRNA failed to affect galangin-induced autophagy. Collectively, the findings
      demonstrated a novel mechanism of how galangin induces autophagy via activating
      AMPK in a LKB1- independent manner. The induction of autophagy can thus reflect
      the anti-proliferation effect of galangin in HCC cells. 

PMID- 24028943
TI  - Citation opportunity cost of the high impact factor obsession.

PMID- 24028941
TI  - Design and conduct of 'Xtreme Alps': a double-blind, randomised controlled study
      of the effects of dietary nitrate supplementation on acclimatisation to high
      altitude.
AB  - The study of healthy human volunteers ascending to high altitude provides a
      robust model of the complex physiological interplay that emulates human
      adaptation to hypoxaemia in clinical conditions. Nitric oxide (NO) metabolism may
      play an important role in both adaptation to high altitude and response to
      hypoxaemia during critical illness at sea level. Circulating nitrate and nitrite
      concentrations can be augmented by dietary supplementation and this is associated
      with improved exercise performance and mitochondrial efficiency. We hypothesised
      that the administration of a dietary substance (beetroot juice) rich in nitrate
      would improve oxygen efficiency during exercise at high altitude by enhancing
      tissue microcirculatory blood flow and oxygenation. Furthermore, nitrate
      supplementation would lead to measurable increases in NO bioactivity throughout
      the body. This methodological manuscript describes the design and conduct of the
      'Xtreme Alps' expedition, a double-blind randomised controlled trial
      investigating the effects of dietary nitrate supplementation on acclimatisation
      to hypobaric hypoxia at high altitude in healthy human volunteers. The primary
      outcome measure was the change in oxygen efficiency during exercise at high
      altitude between participants allocated to receive nitrate supplementation and
      those receiving a placebo. A number of secondary measures were recorded,
      including exercise capacity, peripheral and microcirculatory blood flow and
      tissue oxygenation. Results from this study will further elucidate the role of NO
      in adaption to hypoxaemia and guide clinical trials in critically ill patients.
      Improved understanding of hypoxaemia in critical illness may provide new
      therapeutic avenues for interventions that will improve survival in critically
      ill patients. 

PMID- 24028944
TI  - Gemmata obscuriglobus.

PMID- 24028942
TI  - Family, community and clinic collaboration to treat overweight and obese
      children: Stanford GOALS-A randomized controlled trial of a three-year, multi
      component, multi-level, multi-setting intervention.
AB  - OBJECTIVE: To test the effects of a three-year, community-based, multi-component,
      multi-level, multi-setting (MMM) approach for treating overweight and obese
      children. DESIGN: Two-arm, parallel group, randomized controlled trial with
      measures at baseline, 12, 24, and 36 months after randomization. PARTICIPANTS:
      Seven through eleven year old, overweight and obese children (BMI >= 85th
      percentile) and their parents/caregivers recruited from community locations in
      low-income, primarily Latino neighborhoods in Northern California. INTERVENTIONS:
      Families are randomized to the MMM intervention versus a community health
      education active-placebo comparison intervention. Interventions last for three
      years for each participant. The MMM intervention includes a community-based after
      school team sports program designed specifically for overweight and obese
      children, a home-based family intervention to reduce screen time, alter the home
      food/eating environment, and promote self-regulatory skills for eating and
      activity behavior change, and a primary care behavioral counseling intervention
      linked to the community and home interventions. The active-placebo comparison
      intervention includes semi-annual health education home visits, monthly health
      education newsletters for children and for parents/guardians, and a series of
      community-based health education events for families. MAIN OUTCOME MEASURE: Body
      mass index trajectory over the three-year study. Secondary outcome measures
      include waist circumference, triceps skinfold thickness, accelerometer-measured
      physical activity, 24-hour dietary recalls, screen time and other sedentary
      behaviors, blood pressure, fasting lipids, glucose, insulin, hemoglobin A1c, C
      reactive protein, alanine aminotransferase, and psychosocial measures.
      CONCLUSIONS: The Stanford GOALS trial is testing the efficacy of a novel
      community-based multi-component, multi-level, multi-setting treatment for
      childhood overweight and obesity in low-income, Latino families.

PMID- 24028945
TI  - Practicing memory retrieval improves long-term retention in rats.
AB  - The view that the human mind is a repository of stored items dates at least to
      Aristotle and Plato and continues to dominate investigations of human memory.
      This view fits with our intuitions that we study information as the optimal
      method to store information in memory and that retrieval of information functions
      only to assess what information was previously stored. Yet modern research on
      human memory suggests that retrieving information during a test facilitates later
      memory of that information. Because human memory is intertwined with language, it
      is difficult to resist the conclusion that language is essential for this key
      aspect of human cognition. Here we show that practising memory retrieval improves
      long-term retention in a nonhuman species. We report evidence that rats' long
      term memory performance is enhanced if they had previously retrieved specific
      items stored in memory.

PMID- 24028946
TI  - Visual sensory networks and effective information transfer in animal groups.
AB  - Social transmission of information is vital for many group-living animals,
      allowing coordination of motion and effective response to complex environments.
      Revealing the interaction networks underlying information flow within these
      groups is a central challenge. Previous work has modeled interactions between
      individuals based directly on their relative spatial positions: each individual
      is considered to interact with all neighbors within a fixed distance (metric
      range), a fixed number of nearest neighbors (topological range), a 'shell' of
      near neighbors (Voronoi range), or some combination (Figure 1A). However,
      conclusive evidence to support these assumptions is lacking. Here, we employ a
      novel approach that considers individual movement decisions to be based
      explicitly on the sensory information available to the organism. In other words,
      we consider that while spatial relations do inform interactions between
      individuals, they do so indirectly, through individuals' detection of sensory
      cues. We reconstruct computationally the visual field of each individual
      throughout experiments designed to investigate information propagation within
      fish schools (golden shiners, Notemigonus crysoleucas). Explicitly considering
      visual sensing allows us to more accurately predict the propagation of behavioral
      change in these groups during leadership events. Furthermore, we find that
      structural properties of visual interaction networks differ markedly from those
      of metric and topological counterparts, suggesting that previous assumptions may
      not appropriately reflect information flow in animal groups.

PMID- 24028947
TI  - Active vision: microsaccades direct the eye to where it matters most.
AB  - Even in the most sensitive part of human retina, the fovea, perception is not
      uniform. To compensate for such non-uniformity, tiny fixational microsaccades
      direct the optimal foveal locus to relevant parts of the fixated scene, similarly
      to larger exploratory saccades but on a miniature scale.

PMID- 24028948
TI  - Carnivorous plants: trapping, digesting and absorbing all in one.
AB  - The Venus flytrap digests and absorbs its prey, but how does it coordinate
      digestion and absorption to maximise the efficiency of this highly evolved
      mechanism? A new study that combines direct recordings from cells within the trap
      along with molecular characterization of nutrient transport reveals a complex and
      coordinated suite of mechanisms that underlie this elegant process.

PMID- 24028949
TI  - Speed control: spinal interneurons with crossed purposes.
AB  - A recent study has revealed that different populations of commissural spinal
      interneurons ensure limb alternation at different speeds of locomotion. 

PMID- 24028950
TI  - Active vision: adapting how to look.
AB  - A new study has found that artificial occlusion of central vision leads to rapid
      emergence, and long-term maintenance of a new preferred retinal locus of
      fixation. These findings have important implications for the understanding of
      visual and oculomotor plasticity as well as for the development of rehabilitation
      techniques. 

PMID- 24028951
TI  - Neuronal development: SAD kinases make happy axons.
AB  - The polarity proteins LKB1 and SAD-A/B are key regulators of axon specification
      in the developing cerebral cortex. Recent studies now show that this mechanism
      cannot be generalized to other classes of neurons: instead, SAD-A/B functions
      downstream of neurotrophin signaling in sensory neurons to mediate a later stage
      of axon development - arborization in the target field.

PMID- 24028952
TI  - Evolution: a bacterially mediated swap meet for adaptive traits.
AB  - New research suggests that secondary bacterial symbionts in insects act as a
      mechanism for horizontal genetic exchange among hosts, facilitating adaptation to
      new ecological niches.

PMID- 24028953
TI  - Recognition memory: an old idea given new life.
AB  - A new study combining behavioral and physiological approaches has given new life
      to the old idea that the hippocampus is critically involved in familiarity-based
      recognition memory. 

PMID- 24028954
TI  - A biological perspective on memory.

PMID- 24028955
TI  - Cultural memory.
AB  - Humans have a form of externalised memory. They are able to transmit information
      across generations in the form of learned cultural traditions and preserve this
      knowledge in artefacts. How this capability evolved from the simpler traditions
      of other animals is an active area of research. 

PMID- 24028956
TI  - The biochemistry of memory.
AB  - Almost fifty years ago, Julius Adler initiated a program of research to gain
      insights into the basic biochemistry of intelligent behavior by studying the
      molecular mechanisms that underlie the chemotactic responses of Escherichia coli.
      All living organisms share elements of a common biochemistry for metabolism,
      growth and heredity - why not intelligence? Neurobiologists have demonstrated
      that this is the case for nervous systems in animals ranging from worms to man.
      Motile unicellular organisms such as E. coli exhibit rudimentary behaviors that
      can be loosely described in terms of cognitive phenomena such as memory and
      learning. Adler's initiative at least raised the prospect that, because of the
      numerous experimental advantages provided by E. coli, it would be the first
      organism whose behavior could be understood at molecular resolution. 

PMID- 24028957
TI  - Memory reconsolidation.
AB  - The formation, storage and use of memories is critical for normal adaptive
      functioning, including the execution of goal-directed behavior, thinking, problem
      solving and decision-making, and is at the center of a variety of cognitive,
      addictive, mood, anxiety, and developmental disorders. Memory also significantly
      contributes to the shaping of human personality and character, and to social
      interactions. Hence, understanding how memories are formed, stored, retrieved,
      modified, updated and used potentially impacts many areas in human life,
      including mental health. 

PMID- 24028958
TI  - Prospective memory.

PMID- 24028959
TI  - Shocking revelations and saccharin sweetness in the study of Drosophila olfactory
      memory.
AB  - It is now almost forty years since the first description of learning in the fruit
      fly Drosophila melanogaster. Various incarnations of the classic mutagenesis
      approach envisaged in the early days have provided around one hundred learning
      defective mutant fly strains. Recent technological advances permit temporal
      control of neural function in the behaving fly. These approaches have radically
      changed experiments in the field and have provided a neural circuit perspective
      of memory formation, consolidation and retrieval. Combining neural perturbations
      with more classical mutant intervention allows investigators to interrogate the
      molecular and cellular processes of memory within the defined neural circuits.
      Here, we summarize some of the progress made in the last ten years that indicates
      a remarkable conservation of the neural mechanisms of memory formation between
      flies and mammals. We emphasize that considering an ethologically-relevant
      viewpoint might provide additional experimental power in studies of Drosophila
      memory.

PMID- 24028960
TI  - Interplay of hippocampus and prefrontal cortex in memory.
AB  - Recent studies on the hippocampus and the prefrontal cortex have considerably
      advanced our understanding of the distinct roles of these brain areas in the
      encoding and retrieval of memories, and of how they interact in the prolonged
      process by which new memories are consolidated into our permanent storehouse of
      knowledge. These studies have led to a new model of how the hippocampus forms and
      replays memories and how the prefrontal cortex engages representations of the
      meaningful contexts in which related memories occur, as well as how these areas
      interact during memory retrieval. Furthermore, they have provided new insights
      into how interactions between the hippocampus and prefrontal cortex support the
      assimilation of new memories into pre-existing networks of knowledge, called
      schemas, and how schemas are modified in this process as the foundation of memory
      consolidation. 

PMID- 24028962
TI  - Spatial memory in insect navigation.
AB  - A wide variety of insects use spatial memories in behaviours like holding a
      position in air or flowing water, in returning to a place of safety, and in
      foraging. The Hymenoptera, in particular, have evolved life-histories requiring
      reliable spatial memories to support the task of provisioning their young.
      Behavioural experiments, primarily on social bees and ants, reveal the mechanisms
      by which these memories are employed for guidance to spatial goals and suggest
      how the memories, and the processing streams that use them, may be organized. We
      discuss three types of memory-based guidance which, together, can explain a large
      part of observed insect spatial behaviour. Two of these, alignment image-matching
      and positional image-matching, are based on an insect's remembered views of its
      surroundings: The first uses views to keep to a familiar heading and the second
      to head towards a familiar place. The third type of guidance is based on a
      process of path integration by which an insect monitors its distance and
      direction from its nest through odometric and compass information. To a large
      degree, these guidance mechanisms appear to involve modular computational
      systems. We discuss the lack of evidence for cognitive maps in insects, and in
      particular the evidence against a map based on path integration, in which view
      based and path integration memories might be combined. We suggest instead that
      insects have a collective of separate guidance systems, which cooperate and train
      each other, and together provide reliable guidance over a range of conditions. 

PMID- 24028961
TI  - Sleep, plasticity and memory from molecules to whole-brain networks.
AB  - Despite the ubiquity of sleep across phylogeny, its function remains elusive. In
      this review, we consider one compelling candidate: brain plasticity associated
      with memory processing. Focusing largely on hippocampus-dependent memory in
      rodents and humans, we describe molecular, cellular, network, whole-brain and
      behavioral evidence establishing a role for sleep both in preparation for initial
      memory encoding, and in the subsequent offline consolidation of memory. Sleep and
      sleep deprivation bidirectionally alter molecular signaling pathways that
      regulate synaptic strength and control plasticity-related gene transcription and
      protein translation. At the cellular level, sleep deprivation impairs cellular
      excitability necessary for inducing synaptic potentiation and accelerates the
      decay of long-lasting forms of synaptic plasticity. In contrast, rapid eye
      movement (REM) and non-rapid eye movement (NREM) sleep enhance previously induced
      synaptic potentiation, although synaptic de-potentiation during sleep has also
      been observed. Beyond single cell dynamics, large-scale cell ensembles express
      coordinated replay of prior learning-related firing patterns during subsequent
      NREM sleep. At the whole-brain level, somewhat analogous learning-associated
      hippocampal (re)activation during NREM sleep has been reported in humans.
      Moreover, the same cortical NREM oscillations associated with replay in rodents
      also promote human hippocampal memory consolidation, and this process can be
      manipulated using exogenous reactivation cues during sleep. Mirroring molecular
      findings in rodents, specific NREM sleep oscillations before encoding refresh
      human hippocampal learning capacity, while deprivation of sleep conversely
      impairs subsequent hippocampal activity and associated encoding. Together, these
      cross-descriptive level findings demonstrate that the unique neurobiology of
      sleep exerts powerful effects on molecular, cellular and network mechanisms of
      plasticity that govern both initial learning and subsequent long-term memory
      consolidation.

PMID- 24028963
TI  - Episodic memory in nonhuman animals.
AB  - Episodic memories differ from other types of memory because they represent
      aspects of the past not present in other memories, such as the time, place, or
      social context in which the memories were formed. Focus on phenomenal experience
      in human memory, such as the sense of 'having been there', has resulted in
      conceptualizations of episodic memory that are difficult or impossible to apply
      to nonhuman species. It is therefore a significant challenge for investigators to
      agree on objective behavioral criteria that can be applied in nonhuman animals
      and still capture features of memory thought to be critical in humans. Some
      investigators have attempted to use neurobiological parallels to bridge this gap;
      however, defining memory types on the basis of the brain structures involved
      rather than on identified cognitive mechanisms risks missing crucial functional
      aspects of episodic memory, which are ultimately behavioral. The most productive
      way forward is likely a combination of neurobiology and sophisticated cognitive
      testing that identifies the mental representations present in episodic memory.
      Investigators that have refined their approach from asking the naive question "do
      nonhuman animals have episodic memory" to instead asking "what aspects of
      episodic memory are shared by humans and nonhumans" are making progress.

PMID- 24028964
TI  - Remembering the prolonged cold of winter.
AB  - Plants have to cope with constantly changing conditions and need to respond to
      environmental stresses and seasonal changes in temperature and photoperiod.
      Alignment of their development with particular seasons requires memory mechanisms
      and an ability to integrate noisy temperature signals over long time scales. An
      increasingly well understood example of how seasonal changes influence
      development is vernalization, the acceleration of flowering by prolonged cold.
      Vernalization has been dissected in Arabidopsis thaliana and shown to involve a
      Polycomb-based epigenetic memory system. This minireview summarizes our current
      understanding of this mechanism and its modulation through adaptation. A key
      concept that has emerged is that cell-autonomous switching between epigenetic
      states can provide the basis for quantitative accumulation of environmental
      memory.

PMID- 24028965
TI  - Building synthetic memory.
AB  - Cellular memory - conversion of a transient signal into a sustained response - is
      a common feature of biological systems. Synthetic biologists aim to understand
      and re-engineer such systems in a reliable and predictable manner. Synthetic
      memory circuits have been designed and built in vitro and in vivo based on
      diverse mechanisms, such as oligonucleotide hybridization, recombination,
      transcription, phosphorylation, and RNA editing. Thus far, building these
      circuits has helped us explore the basic principles required for stable memory
      and ask novel biological questions. Here we discuss strategies for building
      synthetic memory circuits, their use as research tools, and future applications
      of these devices in medicine and industry.

PMID- 24028967
TI  - Histopathological and immunohistochemical profile in anaplastic gangliogliomas.
AB  - BACKGROUND: The anaplastic ganglioglioma (AG) is the high-grade counterpart of
      ganglioglioma, a rare mixed tumor composed of neuronal/ganglion and glial cells.
      MATERIALS AND METHODS: We describe the histopathology and immunohistochemistry in
      7 cases of AG and correlate them with the clinical and radiological features.
      RESULTS: Our AG patients correspond to 2.5% of the central nervous system tumor
      patients evaluated in our institution. The mean age at presentation was 25.7
      years, with a male predominance. The most common clinical presentation was
      generalized tonic-clonic seizures (3/7 cases), in correlation with frequent
      cortical/subcortical location (6/7 cases). Histopathologically, all our cases
      showed high-grade features in glial (glial fibrillary acid protein-positive) and
      neuron-ganglion cells (synaptophysin, PGP-9.5, neurofilament, NSE and CD56
      positive), as well as moderate cellularity, frequent mitotic figures and a Ki-67
      labeling index >5%. All our patients had poor survival. CONCLUSION: We found that
      a typical histopathological and immunohistochemical profile is constant and can
      be useful in early diagnosis of these aggressive neoplasms.

PMID- 24028966
TI  - Evidence for natural killer cell memory.
AB  - Natural killer (NK) cells are generally considered to be part of the innate
      immune system. Over the past few years, however, evidence has accumulated
      suggesting that NK cells have certain features that are characteristic of the
      adaptive immune system. NK cells reportedly respond in an antigen-specific manner
      to a variety of small molecules and certain viruses, and mediate enhanced
      responses to these antigens upon secondary exposure. In infections with mouse
      cytomegalovirus (MCMV), MCMV-specific NK cells undergo clonal expansion, and
      display increased effector function after the resolution of the infection. In
      addition, inflammatory conditions resulting from exposure to certain cytokines
      seem to promote prolonged effector function in NK cells in an antigen-non
      specific fashion. Taken together, these studies reveal new aspects of NK biology,
      and suggest that NK cells, like T and B cells, may carry out memory responses and
      may also exhibit greater capacity to distinguish antigens than was previously
      recognized. 

PMID- 24028968
TI  - Antioxidant and anti-inflammatory flavonol glucuronides from Polygonum aviculare
      L.
AB  - A series of 11 flavonol glucuronides were isolated from the herb of Polygonum
      aviculare L. (Ph.Eur) of which 8 were reported for the first time from the
      Polygonum species. Three acetylated kaempferol and isorhamnetin glucuronides were
      isolated from a natural source for the first time. All compounds, including the
      new ones, were characterized using 1D and 2D NMR spectra as well as high
      resolution mass spectrometry. The influence of all isolated compounds on the
      production of reactive oxygen species, as well as on elastase release by human
      neutrophils, was evaluated in in vitro studies. The results showed that all
      investigated compounds at physiologically achievable concentrations within the
      range of 0.5-10 MUM significantly inhibited the production of reactive oxygen
      species as well as elastase release in human neutrophils model and should be
      considered as responsible for anti-inflammatory activity of the P. aviculare
      herb. The chemotaxonomic value of isolated compounds was also discussed.

PMID- 24028969
TI  - Monoterpenes with antibacterial activities from a Cameroonian medicinal plant
      Canthium Multiflorum (Rubiaceae).
AB  - Investigation of the crude extract obtained from the aerial parts of Canthium
      multiflorum led to the isolation of a new iridoid (1) together with twelve known
      compounds. The structures of these compounds were elucidated by interpretation of
      1D and 2D NMR spectroscopic data, accurate mass measurements and comparison with
      analytical data of previously known analogues. Most of the isolated compounds
      have been reported for the first time from C. multiflorium. The antimicrobial
      activities of the isolated compounds were evaluated on five different bacterial
      strains using agar diffusion technique. The Gram-positive bacterium
      Staphylococcus aureus subsp. aureus (DSM 799), and the Gram-negative bacteria
      Actinobacter calco-aceticus (DSM 30006), Serratia plymuthica (DSM 4540),
      Pseudomonas stutzeri (DSM 4166) and Escherichia coli (DSM 1116) were employed for
      this purpose. The new iridoid, named 6-oxo-genipin (1), demonstrated significant
      inhibitory activity against all microbial strains tested, especially the pathogen
      Staphylococcus aureus. In addition, the compounds 3, 4 and 9 exhibited
      antiplasmodial activity against Plasmodium falciparum strain K1 and weak
      cytotoxicity against L6 cell lines. 

PMID- 24028970
TI  - Chemical constituents of Aloe barbadensis Miller and their inhibitory effects on
      phosphodiesterase-4D.
AB  - Aloe barbadensis Mill has been used as food and medicine for a long time. In
      order to investigate the chemical constituents of A. barbadensis and their
      inhibitory activities towards phosphodiesterase-4D (PDE4D), 70% methanol extract
      of the dried A. barbadensis powder was employed. Phytochemical investigation has
      led to the isolation of three new chromones, 5-(hydroxymethyl)-7-methoxy-2
      methylchromone (4), 5-((4E)-2'-oxo-pentenyl)-2-hydroxymethylchromone (6), and 7
      hydroxy-5-(hydroxymethyl)-2-methylchromone (7), together with eighteen known
      compounds. Their chemical structures were determined based on spectroscopic
      methods including UV, IR, 1D and 2D NMR, and HRMS spectrometry. In addition,
      their inhibition against PDE4D was evaluated using tritium-labeled adenosine
      3',5'-cyclic monophosphate ((3)H-cAMP) as the substrate. Inhibition was
      calculated by the variation of radioactivity after the reaction, and compounds 1
      4, 10, and 21 exhibited certain inhibitory activities towards PDE4D, which can
      provide an explanation why A. barbadensis can serve as anti-inflammatory agents. 

PMID- 24028971
TI  - MiR-9 reduces human acyl-coenzyme A:cholesterol acyltransferase-1 to decrease THP
      1 macrophage-derived foam cell formation.
AB  - MicroRNAs (miRNAs) post-transcriptionally regulate gene expression by targeting
      mRNAs and control a wide range of biological functions. Recent studies have
      indicated that miRNAs can regulate lipid and cholesterol metabolism in mammals.
      Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is a key enzyme in cellular
      cholesterol metabolism. The accumulated cholesteryl esters are mainly synthesized
      by ACAT1 during the formation of foam cell, a hallmark of early atherosclerotic
      lesions. Here, we revealed that miR-9 could target the 3'-untranslated region of
      human ACAT1 mRNA, specifically reduce human ACAT1 or reporter firefly luciferase
      (Fluc) proteins but not their mRNAs in different human cell lines, and
      functionally decrease the formation of foam cells from THP-1-derived macrophages.
      Our findings suggest that miR-9 might be an important regulator in cellular
      cholesterol homeostasis and decrease the formation of foam cells in vivo by
      reducing ACAT1 proteins. 

PMID- 24028972
TI  - Over-expression of fibroblast activation protein alpha increases tumor growth in
      xenografts of ovarian cancer cells.
AB  - Fibroblast activation protein alpha (FAPalpha) is a 95-kDa serine protease of
      post-prolyl peptidase family on cell surface. FAPalpha is widely expressed in
      tumor microenvironment. The wide spread association of FAPalpha expression with
      cancer suggests that it has important functions in the disease. However, the
      nature of FAPalpha's roles in cancer cell activity is not well-determined. It has
      been showed that FAPalpha silencing in SKOV3 cells induces ovarian tumors but
      significantly reduces tumor growth in a xenograft mouse model. To further
      determine the role of FAPalpha in epithelial ovarian cancer cells, SKOV3-FAPalpha
      and HO8910-FAPalpha cell lines, which over-expressed FAPalpha stably, were
      constructed and then their biological behaviors were investigated. It was found
      that FAPalpha promoted ovarian cancer cell proliferation, drug resistance,
      invasiveness, and migration in vitro. Immunochemistry assay showed that FAPalpha
      significantly facilitated tumor growth in xenograft tumor tissues. These results
      suggested that FAPalpha might directly promote tumor growth and invasiveness in
      ovarian cancer cells. 

PMID- 24028973
TI  - Common descent of B chromosomes in two species of the fish genus Prochilodus
      (Characiformes, Prochilodontidae).
AB  - To ascertain the origin of B chromosomes in 2 fish species of the genus
      Prochilodus, i.e. P. lineatus and P. nigricans, we microdissected them and
      generated B-specific DNA probes. These probes were used to perform chromosome
      painting in both species and in 3 further ones belonging to the same genus (P.
      argenteus, P. brevis and P. costatus). Both probes hybridized with the B
      chromosomes in P. lineatus and P. nigricans, but with none of the chromosomes in
      the 5 species. This indicates that the B chromosomes have low similarity with
      DNAs located in the A chromosomes and suggests the possibility that the B
      chromosomes in the 2 species have a common origin. The most parsimonious
      explanation would imply intergeneric hybridization in an ancestor of P. lineatus
      and P. nigricans yielding the B chromosome as a byproduct, which remained in
      these 2 species after their phylogenetic origin, but was perhaps lost in other
      Prochilodus species. This hypothesis predicts that B chromosomes are old genomic
      elements in this genus, and this could be tested once a species from a relative
      genus would be found showing homology of its A chromosomes with the B-probes
      employed here, through a comparison of B chromosome DNA sequences with those in
      the A chromosomes of this other species.

PMID- 24028975
TI  - Development of hospital disaster resilience: conceptual framework and potential
      measurement.
AB  - OBJECTIVE: Despite 'hospital resilience' gaining prominence in recent years, it
      remains poorly defined. This article aims to define hospital resilience, build a
      preliminary conceptual framework and highlight possible approaches to
      measurement. METHODS: Searches were conducted of the commonly used health
      databases to identify relevant literature and reports. Search terms included
      'resilience and framework or model' or 'evaluation or assess or measure and
      hospital and disaster or emergency or mass casualty and resilience or capacity or
      preparedness or response or safety'. Articles were retrieved that focussed on
      disaster resilience frameworks and the evaluation of various hospital capacities.
      RESULT: A total of 1480 potentially eligible publications were retrieved
      initially but the final analysis was conducted on 47 articles, which appeared to
      contribute to the study objectives. Four disaster resilience frameworks and 11
      evaluation instruments of hospital disaster capacity were included. DISCUSSION
      AND CONCLUSION: Hospital resilience is a comprehensive concept derived from
      existing disaster resilience frameworks. It has four key domains: hospital
      safety; disaster preparedness and resources; continuity of essential medical
      services; recovery and adaptation. These domains were categorised according to
      four criteria, namely, robustness, redundancy, resourcefulness and rapidity. A
      conceptual understanding of hospital resilience is essential for an intellectual
      basis for an integrated approach to system development. This article (1) defines
      hospital resilience; (2) constructs conceptual framework (including key domains);
      (3) proposes comprehensive measures for possible inclusion in an evaluation
      instrument; and (4) develops a matrix of critical issues to enhance hospital
      resilience to cope with future disasters.

PMID- 24028974
TI  - Longitudinal associations between childhood and adulthood externalizing and
      internalizing psychopathology and adolescent substance use.
AB  - BACKGROUND: Emotional and behavioral problems are commonly associated with
      substance use in adolescence but it is unclear whether substance use precedes or
      follows mental health problems. The aim was to investigate longitudinal
      associations between externalizing and internalizing psychopathology and
      substance use in a prospective population study design. METHOD: The sample was
      the Northern Finland Birth Cohort 1986 Study (NFBC 1986; n = 6349; 3103 males).
      Externalizing and internalizing mental health problems were assessed at age 8
      years (Rutter scales), substance use and externalizing and internalizing problems
      [Youth Self-Report (YSR)] at age 15-16 years, and hospital diagnoses for
      internalizing disorders (age 25) and criminal offences (age 20) from nationwide
      registers in adulthood. RESULTS: Externalizing problems at age 8 were associated
      with later substance use. After adjustment for sociodemographic factors, parental
      alcohol use and psychiatric disorders, and earlier externalizing and
      internalizing problems, substance use predicted criminality, especially among
      males, with the highest odds ratio (OR) for cannabis use [adjusted OR 6.2, 95%
      confidence interval (CI) 3.1-12.7]. Early internalizing problems were not a risk
      for later substance use. Female adolescent cannabis (OR 3.2, 95% CI 1.4-7.3) and
      alcohol (OR 2.1, 95% CI 1.1-4.2) use predicted internalizing disorders in
      adulthood. CONCLUSIONS: Externalizing problems precede adolescent substance use
      in both genders, whereas, among boys, substance use also precedes criminal
      offences. Internalizing problems may follow substance use in females. These
      associations were robust even when taking into account previous mental health
      problems.

PMID- 24028976
TI  - Fluid on the chest.

PMID- 24028977
TI  - Intraoperative inflation of laryngocele with LMA.
AB  - OBJECTIVES: Laryngoceles are pathologic air filled dilations of the laryngeal
      ventricle. They are most often benign and incidental findings. Resection may be
      necessary in the setting of infection, airway obstruction, dysphagia, and
      phonatory disturbances. External laryngoceles are almost universally treated with
      open resection via a lateral or midline cervical approach. Care must be taken to
      resect the laryngocele in its entirety to avoid recurrence. In cases of recurrent
      infection, normal surgical planes are often fibrosed and obscured increasing the
      risk of neurovascular sacrifice and functional losses. METHODS: We are reporting
      a case of recurrent infections in a large, palpable external laryngocele. During
      resection the patient was ventilated using an endotracheal tube (ETT).
      Additionally, a laryngeal mask airway (LMA) was inserted posterior to the ETT,
      resting in the hypopharynx and attached to a Jackson Rees circuit. Air was passed
      through the LMA to inflate the laryngocele and better define its borders. The LMA
      was also used to identify the root of the laryngocele in the paraglottic space
      and ensure its airtight closure. RESULTS: The LMA assisted our dissection and
      helped progress the surgery safely in a fibrosed surgical field. We have not seen
      this method described previously. The patient continues to be free of recurrence
      2 years after surgery. CONCLUSION: While in most cases, with careful surgical
      technique, even a fibrotic and scarred laryngocele can be excised in its entirety
      without neurovascular sacrifice. In some cases where this may be difficult with a
      traditional approach, we offer the intra-operative trumpet maneuver as a viable
      method of better delineating the borders of a laryngocele.

PMID- 24028979
TI  - A Brain Parenchyma Model-Based Segmentation of Intraventricular and Intracerebral
      Haemorrhage in CT Scans.
AB  - Accurate quantification of haemorrhage volume in a computed tomography (CT) scan
      is critical in the management and treatment planning of intraventricular (IVH)
      and intracerebral haemorrhage (ICH). Manual and semi-automatic methods are
      laborious and time-consuming limiting their applicability to small data sets. In
      clinical trials measurements are done at different locations and on a large
      number of data; an accurate, consistent and automatic method is preferred. A fast
      and efficient method based on texture energy for identification and segmentation
      of hemorrhagic regions in the CT scans is proposed. The data set for the study
      was obtained from CLEAR-IVH clinical trial phase III (41 patients' 201 sequential
      CT scans from ten different hospitals, slice thickness 2.5-10 mm and from
      different scanners). The DICOM data were windowed, skull stripped, convolved with
      textural energy masks and segmented using a hybrid method (a combination of
      thresholding and fuzzy c-means). Artifacts were removed by statistical analysis
      and morphological processing. Segmentation results were compared with the ground
      truth. Descriptive statistics, Dice statistical index (DSI), Bland-Altman and
      mean difference analysis were carried out. The median sensitivity, specificity
      and DSI for slice identification and haemorrhage segmentation were 86.25%, 100%,
      0.9254 and 84.90%, 99.94%, 0.8710, respectively. The algorithm takes about one
      minute to process a scan in MATLAB((r)). A hybrid method-based volumetry of
      haemorrhage in CT is reliable, observer independent, efficient, reduces the time
      and labour. It also generates quantitative data that is important for precise
      therapeutic decision-making. 

PMID- 24028978
TI  - Enlarged vestibular aqueduct syndrome mimicking otosclerosis in adults.
AB  - INTRODUCTION: An enlarged vestibular aqueduct (EVA) results in hearing loss which
      is often progressive and heterogenous, the long-term natural history of which is
      not well understood. Patients born before the era of newborn hearing screening
      can present as adults with previously undiagnosed EVA. METHODS: A retrospective
      chart review of patients seen at a tertiary adult academic otologic clinic from
      2004 to 2012 were reviewed and cases of EVA were identified. RESULTS: Adult EVA
      was found to present with a mixed progressive hearing loss with absent stapedial
      reflexes. CONCLUSION: Enlarged vestibular aqueduct abnormality can present in
      adulthood and mimic other more common pathology such as otosclerosis.

PMID- 24028980
TI  - Optimization of Pulse Sequences for Lactate Detection and Its Diagnostic Value in
      Acute Cerebral Infarction Using (1)H MR Spectroscopy.
AB  - Cerebral infarction will cause ischemic encephalopathy and lactate accumulation
      in the brain in acute cerebral infarction. This study investigated the
      optimization of pulse sequences for lactate detection and its diagnostic value in
      acute cerebral infarction using proton MR spectroscopy ((1)H MRS). The studies
      were performed on a phantom and on 17 patients with acute cerebral infarction.
      Examinations were performed with a GE 1.5T MRI system (Signa). The spectra were
      obtained using both PRESS and STEAM sequences. The spectra were processed using a
      GE Advantage workstation (ADW 4.3). Moreover, the optimal sequence combined with
      other sequences, including conventional MRI sequences and MR DWI, were used to
      acquire proton MRI data for 17 patients with acute cerebral infarction and 20
      healthy volunteers. The maximum lactate peaks using TE=135 ms were down doublet
      whereas the peaks using 270 ms were up doublet. Lactate peaks were ascending in
      17 patients with cerebral infarction. Optimized (1)H MRS sequences are useful for
      better detection of lactate in acute cerebral infarction. 

PMID- 24028981
TI  - FMRI activation with an "affective speech" paradigm in vegetative and minimally
      conscious States: applicability and prognostic value.
AB  - Vegetative state (VS) and minimally conscious state (MCS) are considered
      different clinical entities but their differential diagnosis remains challenging.
      Some VS patients can show an MCS-like activation in functional magnetic resonance
      imaging (fMRI) studies that seems to predict recovery from VS. We studied fMRI
      activation with an affective speech paradigm in a cohort of non-communicative
      brain-injured individuals consecutively admitted to a post-acute
      neurorehabilitation facility in five years. Among 93 eligible subjects, 65 met
      the clinical criteria for VS and 28 for MCS. Because of exclusion criteria,
      activation studies were performed in only 30 cases out of 93 and analysed in only
      24 (about 1/4 of the eligible cases): 19 VS and five MCS patients. The passive
      acoustic stimulus consisted in a familiar voice narrating a significant episode
      in the patient's life, administered by nonmagnetic earphones. All the MCS
      patients showed an activation spread to secondary associative cortices but also
      52.7% of the VS patients displayed an "atypical" large-scale activation pattern.
      Regarding the clinical outcome, 80% of the patients with large-scale network
      activation (LSNA) had some recovery of consciousness. Our results confirm that
      the VS patients with LSNA at fMRI study have potential for further recovery of
      consciousness, whereas no patient without activation or only typical activation
      improved. fMRI study with an affective speech paradigm, when applicable, seems to
      have a valuable prognostic value in VS patients, even if there are major
      limitations in terms of applicability. 

PMID- 24028982
TI  - Quantitative evaluation of changes in the selected white matter tracts using
      diffusion tensor imaging in patients with Alzheimer's disease and mild cognitive
      impairment.
AB  - This study evaluated the damage to the extensive range of white matter tracts in
      patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI).
      Thirty-four patients with AD (mean age 71.5 yrs, MMSE 17.6), 23 patients with MCI
      (mean age 66 yrs, MMSE 27.4) and 15 normal controls (mean age 69 yrs, MMSE 29.8)
      were enrolled. Diffusion tensor imaging (DTI) was performed in 25 directions on
      1.5 T MR scanner. Fractional anisotropy (FA) values were obtained with a small
      ROI method in several association tracts including posterior cingulum fibers, in
      commissural tracts (genu and splenium of corpus callosum) and projection tracts
      (middle cerebellar peduncles and posterior limbs of internal capsules). In MCI
      significant reductions of FA were found in the inferior longitudinal fascicles,
      left superior longitudinal fascicle and posterior cingulum fibers compared to
      normal controls. In AD significantly decreased FA values were detected in the
      same fascicles as in MCI and additionally in inferior fronto-occipital tracts and
      commissural tracts. In both AD and MCI the most severe changes were found within
      posterior cingulum fibers. No abnormalities were detected in projection tracts in
      both groups. Accuracy of DTI in detecting AD and MCI reached 0.95 and 0.79,
      respectively. FA measurements strongly correlated with neuropsychological tests.
      DTI is capable of depicting microstructural changes within white matter fiber
      tracts in dementia and may aid the differential diagnosis of AD and MCI. 

PMID- 24028983
TI  - Neuroimaging assessment of spasticity developed after acquired brain injuries and
      multiple sclerosis.
AB  - This study evaluated whether different imaging techniques correlate with specific
      variables routinely used to grade the types and complexities of patient
      conditions in neurorehabilitation services and their clinical outcomes, and if
      there are radiological patterns, topography or distribution of the lesions
      correlated to spasticity. The cohort studied included 75 patients, 38 patients
      with multiple sclerosis (MS) and 37 patients with acquired brain injuries (ABI)
      referred to the neurorehabilitation department from April 2009 to March 2010.
      Data included age, gender, diagnoses, complications, spasticity, length of stay,
      Rehabilitation Complexity Scale (RCS) and Northwick Park Dependency (NPDS) scores
      on admission and discharge. Forward stepwise multiple regressions were performed
      considering Spasticity as dependent and considering NPDS, RCS on admission and
      discharge, age, gender and length of stay as independent variables. Standardized
      intra-axial lesions in those with spasticity were fused with standardized axial
      DTIs from normal controls obtained under 3 T and 1.5 T MRI scanners. Spasticity
      was present in 36 patients. Regression was found between spasticity and all the
      other variables with r = 0.42, r(2) = 0.17, adjr(2) = 0.12(r), F(4,66) = 3.53, p
      < 0.01. Residuals were acceptable. If the same is calculated excluding MS
      patients the results are higher with: r = 0.59, r(2) = 0.35, adjr(2) = 0.30,
      F(2,27) = 7.1885, p < 0.003. In MS subjects, spasticity appeared if lesions
      affected pyramidal tracts, callosal radiations extensively or brainstem. Those
      with ABI did develop spasticity if the lesion involved the internal capsules,
      pericommissural areas, optochiasmatic cistern or brainstem. Findings suggest that
      NPDSa and discharge and RCSd are higher in those developing spasticity. No
      obvious correlation between spasticity and RCSa was found. Subjects with MS are
      more likely to develop spasticity especially if the lesions are numerous and
      affect the corticospinal tracts, callosal radiations extensively or brainstem. In
      patients with ABI lesions affecting pyramidal tracts, pericommissural areas and
      optochiasmatic cisterns seem more likely to develop spasticity. 

PMID- 24028984
TI  - Transient Brain Lesions in Neuro-Behcet's Disease without Systemic Involvement.
AB  - In neuro-Behcet's disease nervous involvement may occasionally precede somatic
      manifestations, making the diagnosis challenging. The reported case showed only a
      neurologic onset with relapsing-remitting form, transient brain MRI abnormalities
      and late appearance of typical muco-cutaneous lesions, thereby delaying the
      correct diagnosis and appropriate treatment. MRI revealed cerebral alterations
      mimicking demyelinating disease, but lesions rapidly disappeared on close follow
      up scans indicating vasogenic edema. Being aware of this atypical presentation
      and recognizing these transient abnormalities may be useful for a prompt
      diagnosis. 

PMID- 24028985
TI  - Anaplastic ganglioglioma of the brainstem in an adult.
AB  - Gangliogliomas are neoplasms with neuronal and glial components. The most common
      location is the temporal lobe and for that reason those patients have seizures as
      the major complaint. Gangliogliomas with anaplastic features are uncommon. A 33
      year-old man presented with a two-year history of progressively worsening right
      sided weakness and contractures. Physical examination demonstrated right-sided
      weakness and contractures involving the upper and lower extremities. Magnetic
      resonance demonstrated multiple nodules involving the tegmental pons with a small
      projection into the prepontine cistern on the left, midbrain tegmentum on the
      left in the subthalamic region. The patient was studied by MRI on T1WI, T2WI,
      FLAIR, DWI, and magnetic resonance spectroscopy. He underwent a craniotomy and
      biopsy of the mass. Histological examination of the specimen revealed glial
      proliferation. Based on these findings the pathologic diagnosis was anaplastic
      ganglioglioma. Only one previous report of an anaplastic astrocytoma in the
      cerebello-pontine angle in an adult has been published. In children three cases
      were reported, only one with magnetic resonance. Our case showed multiple nodular
      structures hypointense on T1 and hyperintense on T2 and FLAIR with enhancement on
      T1 after injection of paramagnetic contrast. Only in this contribution T2 value
      were diffusion-weighted and ADC characteristics and (1)H spectroscopy analyzed. 

PMID- 24028986
TI  - Magnetic resonance imaging of cerebellar liponeurocytoma. A case report and
      review of the literature.
AB  - Cerebellar liponeurocytoma is a rare benign neuroepithelial tumour. We describe
      the case of a 50-year-old man presenting with signs of increased intracranial
      pressure and cerebellar dysfunction. Magnetic resonance imaging showed a
      heterogeneous, well-circumscribed cerebellar mass with a predominant adipose
      content. Diffusion-weighted imaging showed an isointense mass with a hyperintense
      rim. Craniotomy demonstrated a soft grey mass with intratumoral bright patchy
      yellow areas. Histological and immunohistochemical findings indicated an advanced
      neuronal, glial and focal lipomatous differentiation with a low level of mitotic
      activity. 

PMID- 24028987
TI  - Surgical management and role of medical therapy in ruptured aneurysmal
      neurocysticercosis. A case report and review of the literature.
AB  - We describe the case of an 80-year-old Hispanic male with an acute subarachnoid
      hemorrhage (SAH) due to an inflammatory middle cerebral artery (MCA) aneurysm
      rupture. Two years prior to this episode, the patient had undergone a resection
      of a left intracranial neurocysticercosis lesion. A current CT, CTA and MRI
      showed significant SAH, a left MCA aneurysm and a cystic lesion compatible with
      neurocysticercosis. Intraoperatively, this aneurysm was found to be adjacent to a
      neurocysticercosis cyst, a diagnosis confirmed by surgical pathology. Only a few
      cases of subarachnoid hemorrhage due to an inflammatory brain aneurysm have been
      reported. Due to the associated higher incidence of intraoperative rupture and
      difficulty clipping, our paper highlights the importance of considering an
      inflammatory origin in patients with a history of neurocysticercosis and
      subarachnoid hemorrhage. This is the oldest patient on record reported for this
      diagnosis and surgery. 

PMID- 24028988
TI  - Analysis of corpus callosum diffusion tensor imaging parameters in infants.
AB  - Radial diffusivity is a diffusion tensor imaging (DTI) metric that has received
      increased attention in recent studies as a parameter that may better reflect
      myelination than the more commonly-used fractional anisotropy (FA). This study
      compared rates of radial diffusivity decrease against FA increase and axial
      diffusivity decrease on DTI maps in the corpus callosum of normal infants during
      the first postnatal year. Fifty-three normal infants (range: 0-52 weeks adjusted
      for gestational age) underwent six-direction DTI on a 1.5 Tesla scanner (b= 1,000
      s/mm(2), one excitation). A single individual placed regions of interest on FA
      maps in the genu 1) and radial diffusivity (i.e., lambda and splenium to obtain
      axial (i.e., 3)/2]), FA and ADC. We calculated mean and median values for FA,
      lambda 2+lambda[ ADC, radial diffusivity and axial diffusivity in each of four 13
      week epochs and measured the percent change over the first year of life. Within
      the genu, radial diffusivity decreased 36%, FA increased 25%, ADC decreased 22%
      and axial diffusivity decreased 10%. Within the splenium, radial diffusivity
      decreased 53%, FA increased 43%, ADC decreased 38%, and axial diffusivity
      decreased 23%. For both genu and splenium, the greatest difference was seen in
      radial diffusivity values, followed in order by FA, ADC and axial diffusivity.
      Furthermore, decreases in radial diffusivity were on the order of two to
      threefold greater than those in axial diffusivity. The high rate of radial
      diffusivity decrease compared to axial diffusivity decrease is consistent with
      myelination. Decreases in radial diffusivity were greater than increases in FA
      values. This finding is further support of the concept that radial diffusivity
      and FA values represent two different types of microstructural change during
      development of white matter. 

PMID- 24028989
TI  - Association of pulsatility index in the middle cerebral artery with intelligence
      quotient in children with sickle cell disease.
AB  - The aim of this study was to explore whether intellectual performance in children
      with Sickle Cell Disease and with low risk of stroke as determined with
      conventional transcranial Doppler ultrasonography (TCD) criteria was associated
      with hemodynamic parameters in imaging TCD, when controlling for hematological
      and socio-economical variables and presence of silent infarcts. We performed
      neuropsychological testing with Kaufman Brief Intelligence Test (K-BIT-IQ) and
      imaging TCD examinations to measure blood flow velocities and pulsatility indexes
      (PI) in the middle cerebral arteries (MCA) In 46 children with homozygous HbSS
      (mean age 108+/-34 months, range limits: 47-166 months; 24 females), without a
      history of stroke or transient ischemic attack, with no stenosis on magnetic
      resonance angiography and with velocities below 170 cm/s in screening
      conventional TCD. Mean K-BIT IQ Composite and Vocabulary scores (91+/-13 and 86+/
      14 respectively) were significantly below the average scores of 100 for the age
      matched population (one sample t-test=5.21, p<0.001). Using univariate and
      multivariate regression models, we found that lower PI in the right MCA was
      associated with lower K-BIT-IQ Composite and Vocabulary scores. Furthermore, we
      found that interhemispheric differences in PIs were even more strongly associated
      with neuropsychological performance, whereas flow velocities were not associated
      with the K-BIT-IQ score. Using a model of chronic anemia, we found that cognitive
      functioning was associated with cerebral hemodynamics. 

PMID- 24028990
TI  - Duplicated pituitary gland and odontoid process. A case report.
AB  - The development of the pituitary gland is not well understood, but duplication of
      the gland, a rare embryonic anomaly, may shed some light on the process. Since
      1880 only about 40 cases have been described. A 56-year-old woman complained of
      chronic bilateral upper extremity paresthesia and numbness along her first three
      fingers relieved by rest and exacerbated by increased activity. Magnetic
      resonance imaging of her head and neck showed an incidental discovery of a
      duplication of the pituitary infundibulum and pituitary fossa. Computed
      tomography of the neck showed congenital fusion of C2 with C3, C4 with C5, C1
      with the occipital bone, and a duplication of the odontoid process. Her physical
      examination and all laboratory data were negative. Only seven patients with a
      pituitary duplication have ever survived beyond puberty. While all of these
      patients had normal mental capabilities, they also all had obvious craniofacial
      malformations. Unlike our patient, all other reported cases of duplicated
      pituitaries have been associated with abnormalities of the face or brain.
      Previously proposed theories for duplicated pituitary glands include failed
      twinning, teratogens, and an extreme form of the median cleft face syndrome. We
      feel that the cleft theory developed by Morton et al. best describes the cause of
      our patient's malformations. Such anomalous presentations will improve our
      understanding of how the pituitary gland develops and the order in which cranial
      structures develop to cause these cranial malformations. 

PMID- 24028991
TI  - Cocaine-induced vasospasm causing spinal cord transient ischemia.
AB  - A 25-year-old woman developed a spinal cord infarction leading to quadriplegia
      and respiratory insufficiency after consuming cocaine and vodka for several days.
      Within five months, she regained full motor and respiratory function. A
      literature review revealed 11 cases of cocaine-induced spinal cord infarction. A
      complete recovery from quadriplegia and respiratory failure following cocaine
      abuse has never been reported to date. The value of diffusion-weighted imaging in
      cocaine-induced spinal cord infarction is here presented and discussed. The
      literature proposes several mechanisms for cocaine-induced infarction including
      vasospasm, arteritis, and thrombosis. In this case, the imaging studies and the
      full recovery suggest that the spinal cord ischemia was secondary to a transient
      vasospasm of the anterior spinal artery. 

PMID- 24028992
TI  - An occult spinal neurenteric cyst associated with congenital hemivertebrae. A
      case report.
AB  - We describe a case of an occult spinal neurenteric cyst associated with
      congenital hemivertebrae. Different intraspinal anomalies, such as neurenteric
      cysts (representing 0.3 to 0.5 % of all spinal tumors) have been reported in
      association with congenital hemivertebrae. Indeed, although CT is the best
      examination to study vertebral anomalies, MRI should be performed in order to
      exclude a more complex dysraphic condition. 

PMID- 24028993
TI  - A rare differential diagnosis for cause of proptosis: skull plasmacytoma.
AB  - True solitary plasmacytoma of the skull without signs of systemic myelomatosis is
      very rare as is orbital involvement. It can be part of generalized disease
      (multiple myeloma) or localized disease, presenting as orbital tumor. We describe
      a case of solitary osseous plasmacytoma of the orbit. This 40-year-old man
      presented with a four month history of proptosis of the left eye, swelling in the
      left orbito-temporal region with a mild decrease in visual acuity. Multidetector
      row computed tomography scan showed a geographic osteolytic, well-demarcated
      lesion involving the greater wing of the sphenoid bone showing homogeneous
      contrast enhancement with extra-axial extension to the middle and anterior
      cranial fossa extension with extraconal extension into the orbit at the right
      side. Fine needle and later biopsy of the lesion revealed plasmacytoma. 

PMID- 24028994
TI  - Errata Corrige: The Neuroradiology Journal 25: 17-21, 2012. Multiple Sclerosis
      Lesions in the Brain: Computer-Assisted Assessment of Lesion Load Dynamics on 3D
      FLAIR MR Images.
AB  - The detection and monitoring of brain lesions caused by multiple sclerosis is
      commonly performed with the use of magnetic resonance imaging. Analysis of a
      large number of images is a time-consuming challenge to the neuroradiologist,
      that can be accelerated with the assistance of computer-detection software. In 98
      baseline and follow-up brain magnetic resonance studies from 88 patients with a
      diagnosis of multiple sclerosis, we employed locally developed lesion-detection
      software to assess temporal change in the load of brain lesions and compared its
      results to routine clinical reports. Analyzing the differences between the follow
      up study and the baseline study, the software displays the results in the form of
      a scrollable axial volume, with the changed lesions highlighted in different
      colors and superimposed on the baseline reference scan. Although disagreements
      between the software and the clinical readers in the detection of changed lesions
      were observed only in 12 (12.2%) cases, the difference reached statistical
      significance (p=0.04). The mean interpretation time with assistance of the
      software was 2.7+/-2.2 minutes. We conclude that the performance of the software
      assisted interpretation in the analysis of change over time in multiple sclerosis
      brain lesions is different from the performance of clinical readers, with a
      possibly shorter assessment time. The software detected more changes from
      baseline than clinical readers, suggesting a higher sensitivity, which will have
      to be confirmed on further analysis. 

PMID- 24028995
TI  - Ventral and dorsal pathways of speech perception: an intracerebral ERP study.
AB  - Recent theory of physiology of language suggests a dual stream dorsal/ventral
      organization of speech perception. Using intra-cerebral Event-related potentials
      (ERPs) during pre-surgical assessment of twelve drug-resistant epileptic
      patients, we aimed to single out electrophysiological patterns during both
      lexical-semantic and phonological monitoring tasks involving ventral and dorsal
      regions respectively. Phonological information processing predominantly occurred
      in the left supra-marginal gyrus (dorsal stream) and lexico-semantic information
      occurred in anterior/middle temporal and fusiform gyri (ventral stream). Similar
      latencies were identified in response to phonological and lexico-semantic tasks,
      suggesting parallel processing. Typical ERP components were strongly left
      lateralized since no evoked responses were recorded in homologous right
      structures. Finally, ERP patterns suggested the inferior frontal gyrus as the
      likely final common pathway of both dorsal and ventral streams. These results
      brought out detailed evidence of the spatial-temporal information processing in
      the dual pathways involved in speech perception. 

PMID- 24028996
TI  - Quantitative localization of premature ventricular contractions using myocardial
      activation ECGI from the standard 12-lead electrocardiogram.
AB  - BACKGROUND: The precise localization of the site of origin of a premature
      ventricular contractions (PVC) prior to ablation would facilitate the planning
      and execution of the electrophysiological procedure. Current electrocardiographic
      imaging (ECGI) techniques require body surface maps, a costly and complex
      procedure, that requires as many as 256 leads to localize the PVC origin. We
      developed and tested a novel myocardial activation based ECGI technique utilizing
      the readily available 12-lead ECG to localize the PVC origin. METHODS: The major
      components of the 12-lead ECGI method are: the source model, proximity effect and
      spatial orientation, volume conductor, and patient specific model of the heart,
      lungs, and thorax as derived from magnetic resonance imaging (MRI). For the PVC
      origin localization, the fastest route algorithm is used on patient specific
      models created by newly developed morphing software. PVC localization by the 12
      lead ECGI was correlated to the site of successful ablation. RESULTS: Seven
      patients that underwent electrophysiological mapping and ablation of PVCs were
      studied. All patients (7/7) had accurate prediction of the PVC origin. However in
      two patients, no specific MRI was used for localization that resulted in an
      incorrect switch between the RV free wall and septum of the RVOT. With patient
      specific models, these latter two cases would likely be localized correctly.
      CONCLUSIONS: This feasibility study of a novel myocardial activation-based ECGI
      using only the standard 12-lead ECG shows promise to localize the origin of PVC.
      This ECGI method yields activation estimates of isochrones on both ventricles
      from which the PVC origin location is derived. This method has the capability to
      localize the PVC from any part of the ventricular endocardium, intra-myocardium
      or epicardium.

PMID- 24028997
TI  - Electrocardiogram lead-specific QRS attenuation in an atypical midventricular
      case of Takotsubo syndrome.

PMID- 24028998
TI  - Prognostic value of average T-wave alternans and QT variability for cardiac
      events in MADIT-II patients.
AB  - BACKGROUND: Identifying which patients might benefit the most from ICD therapy
      remains challenging. We hypothesize that increased T-wave alternans (TWA) and QT
      variability (QTV) provide complementary information for predicting appropriate
      ICD therapy in patients with previous myocardial infarction and reduced ejection
      fraction. METHODS: We analyzed 10-min resting ECGs from MADIT-II patients with
      baseline heart rate >80 beats/min. TWA indices IAA and IAA90 were computed with
      the multilead Laplacian Likelihood ratio method. QTV indices QTVN and QTVI were
      measured using a standard approach. Cox proportional hazard models were adjusted
      considering appropriate ICD therapy and sudden cardiac death (SCD) as endpoints.
      RESULTS: TWA and QTV were measured in 175 patients. Neither QTV nor TWA predicted
      SCD. Appropriate ICD therapy was predicted by combining IAA90 and QTVN after
      adjusting for relevant correlates. CONCLUSION: Increased TWA and QTV are
      independent predictors of appropriate ICD therapy in MADIT-II patients with
      elevated heart rate at baseline.

PMID- 24028999
TI  - Prinzmetal angina attacks with emphasis on ventricular arrythmias.

PMID- 24029000
TI  - Incidence of tuberculosis among anti-tumor necrosis factor users in patients with
      a previous history of tuberculosis.
AB  - BACKGROUND: We aimed to investigate the results of anti-tumor necrosis factor
      (TNF) therapy in patients with a previous history of tuberculosis (TB). METHODS:
      A total of 101 patients with a previous history of TB receiving TNF antagonists
      between December 2004 and September 2012 at the Asan Medical Center in South
      Korea were retrospectively analyzed. RESULTS: The mean age of the 101 subjects
      was 40.4 +/- 16.0 years and 51 patients (50.5%) were male. The underlying immune
      mediated inflammatory diseases (IMIDs) were Crohn's disease in 55 (54.5%),
      rheumatoid arthritis in 27 (26.7%), and ankylosing spondylitis in 13 (12.9%)
      patients. Chest radiography findings were suggestive of previous TB lesions in 33
      (32.7%) patients. The rates of positivity in the tuberculin skin test and
      interferon-gamma release assay were 21.8% (22/101) and 44.6% (45/101),
      respectively. Latent TB infection (LTBI) treatment was initiated in 11 subjects
      (10.9%) based on previous inappropriate anti-TB treatments (n = 10) or recent TB
      contact history (n = 1), irrespective of the LTBI test results. The median follow
      up duration after the initiation of TNF antagonist therapy was 31.5 months.
      Active TB developed, six years after the initiation of TNF antagonist, in one
      patient (1.0%) who had not received LTBI treatment. The incidence rate of TB was
      calculated at 336 per 100,000 person-year (PY). CONCLUSIONS: Patients with IMIDs
      who have a previous history of TB can be treated with TNF antagonists with an
      acceptable incidence of TB, if LTBI treatment is performed based on clinical
      judgments including the adequacy of previous anti-TB treatment and recent contact
      history.

PMID- 24029001
TI  - Receptor for advanced glycation end-products (RAGE) activates divergent signaling
      pathways to augment neurite outgrowth of adult sensory neurons.
AB  - BACKGROUND: The receptor for advanced glycation end-products (RAGE) is implicated
      in neuronal differentiation during embryogenesis and in regulation of peripheral
      nerve regeneration. However, the role of RAGE ligands and the signaling pathways
      utilized by activated RAGE in mediating axon regeneration in adult neurons remain
      unknown. We tested the hypothesis that RAGE signaling modulated neurotrophin
      induced neurite outgrowth in cultured adult sensory neurons. RESULTS: Dorsal root
      ganglia (DRG) neurons from adult rats in vitro were exposed to specific RAGE
      ligands, signal transduction inhibitors and function blocking anti-RAGE IgG to
      assess their impact on neurite outgrowth. RAGE ligands including human glycated
      albumin (HGA), S100 calcium binding protein (S100B) and high mobility group 1
      protein (HMGB1; alternatively termed amphoterin) in the presence of neurotrophins
      elevated neurite outgrowth 2-fold (p<0.05). shRNA to RAGE or anti-RAGE IgG
      blockade of RAGE inhibited neurite outgrowth by 40-90% (p<0.05). Western blotting
      and gene reporter analysis showed RAGE ligands activated NF-kappaB, JAK-STAT and
      ERK pathways. RAGE ligand induction of neurite outgrowth was blocked by
      inhibition of NF-kappaB, JAK-STAT or ERK pathways revealing the necessity for
      combined activation for optimal growth. RAGE ligands rapidly elevated NF-kappaB
      p65 expression in the cytoplasm while triggering translocation of NF-kappaB p50
      to the nucleus. shRNA blockade of p50 demonstrated that translocation of p50 to
      the nucleus was implicated in driving axonal outgrowth. CONCLUSIONS: RAGE
      signaling is a complex mediator of neurotrophin-dependent neurite outgrowth,
      operating through divergent but partly inter-dependent pathways.

PMID- 24029003
TI  - Modulating mGluR5 and 5-HT1A/1B receptors to treat l-DOPA-induced dyskinesia:
      effects of combined treatment and possible mechanisms of action.
AB  - l-DOPA-induced dyskinesia (LID) is a major complication of the pharmacotherapy of
      Parkinson's disease. Emerging approaches to the treatment of LID include negative
      modulation of metabotropic glutamate receptor type 5 (mGluR5) and positive
      modulation of serotonin receptors 5-HT1A/1B. We set out to compare the efficacy
      of these two approaches in alleviating the dyskinesias induced by either l-DOPA
      or a D1 receptor agonist. Rats with unilateral 6-OHDA lesions were treated
      chronically with either l-DOPA or the selective D1-class receptor agonist
      SKF38393 to induce abnormal involuntary movements (AIMs). Rats with stable AIM
      scores received challenge doses of the mGluR5 antagonist, MTEP (2.5 and 5mg/kg),
      or the 5-HT1A/1B agonists 8-OH-DPAT/CP94253 (0.035/0.75 and 0.05/1.0mg/kg).
      Treatments were given either alone or in combination. In agreement with previous
      studies, 5mg/kg MTEP and 0.05/1.0mg/kg 8-OH-DPAT/CP94253 significantly reduced l
      DOPA-induced AIM scores. The two treatments in combination achieved a
      significantly greater effect than each treatment alone. Moreover, a significant
      attenuation of l-DOPA-induced AIM scores was achieved when combining doses of
      MTEP (2.5mg/kg) and 8-OH-DPAT/CP94253 (0.035/0.75mg/kg) that did not have a
      significant effect if given alone. SKF38393-induced AIM scores were reduced by
      MTEP at both doses tested, but not by 8-OH-DPAT/CP94253. The differential
      efficacy of MTEP and 8-OH-DPAT/CP94253 in reducing l-DOPA- versus SKF38393
      induced dyskinesia indicates that these treatments have different mechanisms of
      action. This contention is supported by the efficacy of subthreshold doses of
      these compounds in reducing l-DOPA-induced AIMs. Combining negative modulators of
      mGluR5 with positive modulators of 5-HT1A/1B receptors may therefore achieve
      greater than additive antidyskinetic effects and reduce the dose requirement for
      these drugs in Parkinson's disease. 

PMID- 24029002
TI  - Presenilins regulate the cellular activity of ryanodine receptors differentially
      through isotype-specific N-terminal cysteines.
AB  - Presenilins (PS), endoplasmic reticulum (ER) transmembrane proteins, form the
      catalytic core of gamma-secretase, an amyloid precursor protein processing
      enzyme. Mutations in PS lead to Alzheimer's disease (AD) by altering gamma
      secretase activity to generate pathologic amyloid beta and amyloid plaques in the
      brain. Here, we identified a novel mechanism where binding of a soluble,
      cytosolic N-terminal domain fragment (NTF) of PS to intracellular Ca(2+) release
      channels, ryanodine receptors (RyR), controls Ca(2+) release from the ER. While
      PS1NTF decreased total RyR-mediated Ca(2+) release, PS2NTF had no effect at
      physiological Ca(2+) concentrations. This differential function and isotype
      specificity is due to four cysteines absent in PS1NTF, present, however, in
      PS2NTF. Site-directed mutagenesis targeting these cysteines converted PS1NTF to
      PS2NTF function and vice versa, indicating differential RyR binding. This novel
      mechanism of intracellular Ca(2+) regulation through the PS-RyR interaction
      represents a novel target for AD drug development and the treatment of other
      neurodegenerative disorders that critically depend on RyR and PS signaling. 

PMID- 24029004
TI  - Ictal kissing behavior: neurological and psychodynamic overview.
AB  - This study is based on the psychodynamic and neurological analysis of three
      Turkish patients who displayed ictal kissing automatism during their seizures. To
      unveil the probable underlying causes of their kissing behaviors, all patients
      underwent psychiatric interviews after being evaluated by ictal video-EEG
      recordings. The group consisted of two females (ages 35 and 29) and one male (age
      26). In addition to prominent oral automatisms, each patient also displayed
      behaviors of kissing or blowing kisses to individuals at close proximity.
      Seizures were related to the right temporal lobe in two patients and the left
      temporal lobe in one patient. Magnetic resonance imaging showed mesial temporal
      sclerosis in two of the patients (one left, one right) and was normal in one.
      According to the DSM-IV-TR criteria, each of the three patients also suffered
      from major depression, while the psychodynamic interviews revealed traumatic
      childhood histories and intense unfulfilled affective needs. 

PMID- 24029005
TI  - Robot-aided neurorehabilitation in sub-acute and chronic stroke: does spontaneous
      recovery have a limited impact on outcome?
AB  - BACKGROUND: Robotic neurorehabilitation, thanks to high dosage/intensity training
      protocols, has the potential for a greater impact on impairment. OBJECTIVE: We
      aimed to analyze how time since the acute event may influence the motor recovery
      process during robot-assisted rehabilitation of the upper limb. METHODS: A total
      of 41 patients after stroke were enrolled: 20 in subacute phase, i.e. <= 6 months
      elapsed since their unilateral cerebrovascular accident (CVA), and 21 at chronic
      stage, i.e. > 6 months since CVA. All subjects underwent 30 minutes of robot
      aided rehabilitation twice a day, 5 days a week for at least three weeks of
      training. Patients were evaluated at the start and end of treatment using the
      Fugl-Meyer and Modified Ashworth clinical scales and by a set of robot measured
      kinematic parameters. The time interval from stroke was considered as a grouping
      factor to analyze its impact on time course of recovery. RESULTS: After training
      both groups significantly improved their impairment (F = 44.25, p < 0.001) but
      sub-acute patients showed a greater improvement on the Fugl-Meyer scale than
      chronic patients. The time course of recovery of the kinematic variables showed
      higher time constants of motor improvement in the sub-acute than chronic group,
      but they were one order lower than spontaneous recovery time constants.
      CONCLUSIONS: Spontaneous recovery seems to have a limited impact on the
      improvement of sub-acute patients, most of their changes being likely due to re
      learning during rehabilitation. In addition, a longer recovery time was required
      to maximize outcome in sub-acute than in chronic patients.

PMID- 24029006
TI  - Effects of non-paretic arm exercises using a tubing band on abdominal muscle
      activity in stroke patients.
AB  - BACKGROUND: Abdominal strengthening exercises are important for stroke patients;
      however, there is a lack of research on therapeutic exercises for increasing
      abdominal muscle activity in stroke patients. OBJECTIVE: We investigated the
      effects of non-paretic arm exercises using a tubing band on abdominal muscle
      activity in stroke patients. METHODS: In total, 18 hemiplegic subjects (13 males,
      5 females) were recruited. All subjects performed non-paretic arm exercises
      involving three different shoulder movements (extension, flexion, and horizontal
      abduction) using an elastic tubing band. Surface electromyography (EMG) signals
      were recorded from the rectus abdominis (RA), external oblique (EO), and internal
      oblique (IO) muscles bilaterally during non-paretic arm exercises. RESULTS: EMG
      activities of abdominal muscles during non-paretic arm extension and horizontal
      abduction were increased significantly versus shoulder flexion when subjects
      performed the arm exercise in a seated position. Muscle activity of the EO was
      significantly greater in the paretic than the non-paretic side during non-paretic
      arm extension and horizontal abduction. CONCLUSIONS: We suggest that non-paretic
      arm extension and horizontal abduction exercises using an elastic tubing band may
      be effective in increasing abdominal muscle activity.

PMID- 24029007
TI  - Effects of emotional valence and three-dimensionality of visual stimuli on brain
      activation: an fMRI study.
AB  - BACKGROUND: Examining changes in brain activation linked with emotion-inducing
      stimuli is essential to the study of emotions. Due to the ecological potential of
      techniques such as virtual reality (VR), inspection of whether brain activation
      in response to emotional stimuli can be modulated by the three-dimensional (3D)
      properties of the images is important. OBJECTIVE: The current study sought to
      test whether the activation of brain areas involved in the emotional processing
      of scenarios of different valences can be modulated by 3D. Therefore, the focus
      was made on the interaction effect between emotion-inducing stimuli of different
      emotional valences (pleasant, unpleasant and neutral valences) and visualization
      types (2D, 3D). However, main effects were also analyzed. METHODS: The effect of
      emotional valence and visualization types and their interaction were analyzed
      through a 3 * 2 repeated measures ANOVA. Post-hoc t-tests were performed under a
      ROI-analysis approach. RESULTS: The results show increased brain activation for
      the 3D affective-inducing stimuli in comparison with the same stimuli in 2D
      scenarios, mostly in cortical and subcortical regions that are related to
      emotional processing, in addition to visual processing regions. CONCLUSIONS: This
      study has the potential of clarify brain mechanisms involved in the processing of
      emotional stimuli (scenarios' valence) and their interaction with three
      dimensionality.

PMID- 24029009
TI  - A telerehabilitation program by virtual reality-video games improves balance and
      postural control in multiple sclerosis patients.
AB  - BACKGROUND: Balance and postural control (PC) disorders are frequent motor
      disorder symptoms associated with multiple sclerosis (MS). OBJECTIVE: To
      demonstrate the potential improvements in balance and PC among patients with MS
      who complete a virtual reality telerehabilitation program that represents a
      feasible alternative to physical therapy for situations in which conventional
      treatment is not available. METHODS: 50 patients was recruited. Control group (n
      = 25) received physiotherapy treatment twice a week (40 min per session).
      Experimental group (n = 25) received telerehabilitation treatment using the Xbox
      360(r) console monitored via videoconference. Experimental group attended 40
      sessions, four sessions per week (20 min per session). The treatment schedule
      lasted 10 weeks for both groups. A computerised dynamic posturography and
      clinical outcomes (Berg Balance and Tinettti scales) were used at baseline and at
      the end of the treatment. RESULTS: Results showed an improvement over general
      balance in both groups. Visual preference, the contribution of vestibular
      information, mean response time and Tinetti test yielded significant differences
      in the experimental group. An ANOVA revealed significant between-group post
      treatment differences in the composite equilibrium score, Berg and Tinetti scales
      in the experimental group. CONCLUSION: We suggest that our virtual reality
      program enables anticipatory PC and response mechanisms and might serve as a
      successful therapeutic alternative in situations in which conventional therapy is
      not readily available.

PMID- 24029010
TI  - Action observation training for functional activities after stroke: a pilot
      randomized controlled trial.
AB  - OBJECTIVE: The objective of this study was to compare the effects of action
      observation training and motor imagery training on recovery from chronic stroke.
      METHODS: Thirty patients who were more than six months post stroke participated
      in this study and were randomly allocated to three groups. The action observation
      training group practiced additional action observation training for five 30
      minute sessions over a four-week period. The motor imagery training group
      practiced additional motor imagery training for five 30-minute sessions over a
      four-week period. The following clinical measures were used for assessment of
      dynamic balance and gait abilities: Timed Up and Go Test, Functional Reaching
      Test, Walking Ability Questionnaire, and Functional Ambulation Category.
      Spatiotemporal gait parameters were also collected using a GAITRite system.
      RESULT: Compared with the physical training group, the action observation
      training group showed significant improvement in the Timed Up and Go test, gait
      speed, cadence, and single limb support of the affected side. No significant
      differences in any of the outcome measures were observed between the action
      observation training group and the motor imagery training group. CONCLUSION:
      Action observation training and motor imagery training results in improvement of
      dynamic balance and gait ability. These results suggest the feasibility and
      suitability of action observation training for patients with chronic stroke.

PMID- 24029011
TI  - BN-coated Ca(1-x)Sr(x)S:Eu solid-solution nanowires with tunable red light
      emission.
AB  - We report on the controlled growth of novel BN-coated Ca(1-x)Sr(x)S:Eu nanowires
      via a solid-liquid-solid process. The Ca(1-x)Sr(x)S solid solution forms as one
      dimensional nanowires and has been coated with homogeneous protective BN
      nanolayers. The structure and luminescence properties of this new nanocomposite
      have been systematically investigated. High-spatial-resolution
      cathodoluminescence investigations reveal that effective red color tuning has
      been achieved by tailoring the composition of the Ca(1-x)Sr(x)S nanowires.
      Moreover, codoping of Ce(3+) and Eu(2+) in the CaS nanowire can induce energy
      transfer in the matrix and make it possible to obtain enhanced orange color in
      the nanowires. The BN-coated Ca(1-x)Sr(x)S:Eu solid-solution nanowires are
      envisaged to be valuable red-emitting nanophosphors and useful in advanced
      nanodevices and white LEDs.

PMID- 24029012
TI  - Enzymes involved in l-lactate metabolism in humans.
AB  - l-lactate formation occurs via the reduction of pyruvate catalyzed by lactate
      dehydrogenase. l-lactate removal takes place via its oxidation into pyruvate,
      which may be oxidized or converted into glucose. Pyruvate oxidation involves the
      cooperative effort of pyruvate dehydrogenase, the tricarboxylic acid cycle, and
      the mitochondrial respiratory chain. Enzymes of the gluconeogenesis pathway
      sequentially convert pyruvate into glucose. In addition, pyruvate may undergo
      reversible transamination to alanine by alanine aminotransferase. Enzymes
      involved in l-lactate metabolism are crucial to diabetes pathophysiology and
      therapy. Elevated plasma alanine aminotransferase concentration has been
      associated with insulin resistance. Polymorphisms in the G6PC2 gene have been
      associated with fasting glucose concentration and insulin secretion. In diabetes
      patients, pyruvate dehydrogenase is down-regulated and the activity of pyruvate
      carboxylase is diminished in the pancreatic islets. Inhibitors of fructose 1,6
      bisphosphatase are being investigated as potential therapy for type 2 diabetes.
      In addition, enzymes implicated in l-lactate metabolism have revealed to be
      important in cancer cell homeostasis. Many human tumors have higher LDH5 levels
      than normal tissues. The LDHC gene is expressed in a broad range of tumors. The
      activation of PDH is a potential mediator in the body response that protects
      against cancer and PDH activation has been observed to reduce glioblastoma
      growth. The expression of PDK1 may serve as a biomarker of poor prognosis in
      gastric cancer. Mitochondrial DNA mutations have been detected in a number of
      human cancers. Genes encoding succinate dehydrogenase have tumor suppressor
      functions and consequently mutations in these genes may cause a variety of
      tumors. 

PMID- 24029013
TI  - Diagnosis, risk factors, predisposing factors, and predictive models of delirium.

PMID- 24029014
TI  - White-matter hyperintensities predict delirium after cardiac surgery.
AB  - OBJECTIVES: Postoperative delirium is a common psychiatric disorder among
      patients who undergo cardiac surgery. Although several studies have investigated
      risk factors for delirium after cardiac surgery, the association between delirium
      and cerebral white-matter hyperintensities (WMH) on magnetic resonance (MR)
      imaging has not been previously studied. The aim of this study was to identify
      general risk factors for delirium, as well as to examine the specific
      relationship between WMH and delirium. DESIGN: Retrospective chart review.
      SETTING: University hospital. PARTICIPANTS: A total of 130 patients who underwent
      cardiac surgery. MEASUREMENTS: Variables recorded included patient demographics,
      comorbidities, mental health, laboratory data, surgical information, and
      cerebrovascular disease. The presence of WMH was assessed using MR images. Two
      groups of patients were compared (patients with and without delirium) using both
      univariate and multiple logistic analyses. RESULTS: Delirium occurred in 18
      patients (13.8%) and patients with delirium were significantly older than
      patients who did not develop delirium. The prevalence of severe WMH (Fazekas
      score = 3) was significantly higher in patients with delirium. Three independent
      predictors of delirium were identified: abnormal creatinine (odds ratio [OR]:
      4.5; 95% confidence interval [CI]: 1.4-13.9), severe WMH (OR: 3.9; 95% CI: 1.2
      12.5), and duration of surgery (OR: 1.4; 95% CI: 1.0-1.8). CONCLUSIONS: The
      results of this study suggest that white-matter abnormality is one of the most
      important risk factors for development of delirium after cardiac surgery. These
      factors can be used for prediction and prevention of delirium following cardiac
      surgery.

PMID- 24029015
TI  - Role and outcomes of community health workers in HIV care in sub-Saharan Africa:
      a systematic review.
AB  - INTRODUCTION: The provision of HIV treatment and care in sub-Saharan Africa faces
      multiple challenges, including weak health systems and attrition of trained
      health workers. One potential response to overcome these challenges has been to
      engage community health workers (CHWs). METHODOLOGY: A systematic literature
      search for quantitative and qualitative studies describing the role and outcomes
      of CHWs in HIV care between inception and December 2012 in sub-Saharan Africa was
      performed in the following databases: PubMed, PsychINFO, Embase, Web of Science,
      JSTOR, WHOLIS, Google Scholar and SAGE journals online. Bibliographies of
      included articles were also searched. A narrative synthesis approach was used to
      analyze common emerging themes on the role and outcomes of CHWs in HIV care in
      sub-Saharan Africa. RESULTS: In total, 21 studies met the inclusion criteria,
      documenting a range of tasks performed by CHWs. These included patient support
      (counselling, home-based care, education, adherence support and livelihood
      support) and health service support (screening, referral and health service
      organization and surveillance). CHWs were reported to enhance the reach, uptake
      and quality of HIV services, as well as the dignity, quality of life and
      retention in care of people living with HIV. The presence of CHWs in clinics was
      reported to reduce waiting times, streamline patient flow and reduce the workload
      of health workers. Clinical outcomes appeared not to be compromised, with no
      differences in virologic failure and mortality comparing patients under community
      based and those under facility-based care. Despite these benefits, CHWs faced
      challenges related to lack of recognition, remuneration and involvement in
      decision making. CONCLUSIONS: CHWs can clearly contribute to HIV services
      delivery and strengthen human resource capacity in sub-Saharan Africa. For their
      contribution to be sustained, CHWs need to be recognized, remunerated and
      integrated in wider health systems. Further research focusing on comparative
      costs of CHW interventions and successful models for mainstreaming CHWs into
      wider health systems is needed.

PMID- 24029016
TI  - Trial frequency effects in human temporal bisection: implications for theories of
      timing.
AB  - To contrast the classic version of the Scalar Expectancy Theory (SET) with the
      Behavioral Economic Model (BEM), we examined the effects of trial frequency on
      human temporal judgments. Mathematical analysis showed that, in a temporal
      bisection task, SET predicts that participants should show almost exclusive
      preference for the response associated with the most frequent duration, whereas
      BEM predicts that, even though participants will be biased, they will still
      display temporal control. Participants learned to emit one response (R[S]) after
      a 1.0-s stimulus and another (R[L]) after a 1.5-s stimulus. Then the effects of
      varying the frequencies of the 1.0-s and 1.5-s stimuli were assessed. Results
      were more consistent with BEM than with SET. Overall, this research illustrates
      how the impact of non-temporal factors on temporal discrimination may help us to
      contrast associative models such as BEM with cognitive models such as SET.
      Deciding between these two classes of models has important implications regarding
      the relations between associative learning and timing. This article is part of a
      Special Issue entitled: Associative and Temporal Learning.

PMID- 24029017
TI  - Involvement of protein IF2 N domain in ribosomal subunit joining revealed from
      architecture and function of the full-length initiation factor.
AB  - Translation initiation factor 2 (IF2) promotes 30S initiation complex (IC)
      formation and 50S subunit joining, which produces the 70S IC. The architecture of
      full-length IF2, determined by small angle X-ray diffraction and cryo electron
      microscopy, reveals a more extended conformation of IF2 in solution and on the
      ribosome than in the crystal. The N-terminal domain is only partially visible in
      the 30S IC, but in the 70S IC, it stabilizes interactions between IF2 and the
      L7/L12 stalk of the 50S, and on its deletion, proper N-formyl-methionyl(fMet)
      tRNA(fMet) positioning and efficient transpeptidation are affected. Accordingly,
      fast kinetics and single-molecule fluorescence data indicate that the N terminus
      promotes 70S IC formation by stabilizing the productive sampling of the 50S
      subunit during 30S IC joining. Together, our data highlight the dynamics of IF2
      dependent ribosomal subunit joining and the role played by the N terminus of IF2
      in this process. 

PMID- 24029018
TI  - Initiation factor 2 crystal structure reveals a different domain organization
      from eukaryotic initiation factor 5B and mechanism among translational GTPases.
AB  - The initiation of protein synthesis uses initiation factor 2 (IF2) in prokaryotes
      and a related protein named eukaryotic initiation factor 5B (eIF5B) in
      eukaryotes. IF2 is a GTPase that positions the initiator tRNA on the 30S
      ribosomal initiation complex and stimulates its assembly to the 50S ribosomal
      subunit to make the 70S ribosome. The 3.1-A resolution X-ray crystal structures
      of the full-length Thermus thermophilus apo IF2 and its complex with GDP
      presented here exhibit two different conformations (all of its domains except C2
      domain are visible). Unlike all other translational GTPases, IF2 does not have an
      effecter domain that stably contacts the switch II region of the GTPase domain.
      The domain organization of IF2 is inconsistent with the "articulated lever"
      mechanism of communication between the GTPase and initiator tRNA binding domains
      that has been proposed for eIF5B. Previous cryo-electron microscopy
      reconstructions, NMR experiments, and this structure show that IF2 transitions
      from being flexible in solution to an extended conformation when interacting with
      ribosomal complexes. 

PMID- 24029019
TI  - Reverse engineering the cognitive brain.

PMID- 24029020
TI  - How humans stand out in frontal lobe scaling.

PMID- 24029021
TI  - Osteoporotic fractures and persistent non-fusion of the hand epiphyses caused by
      empty sella syndrome in an adult: a case report.
AB  - We report a case of primary empty sella syndrome (ESS) resulting in osteoporotic
      fractures and persistent non-fusion of the hand epiphyses, and discuss the
      potential pathogenesis of this disease. A 41-year-old man presented with pain in
      the right hand and back after a fall. X-radiographs revealed persistent epiphyses
      and severe osteoporosis. Serum phosphorus and prolactin levels were above normal
      levels, and free triiodothyronine, free thyroxine and testosterone levels were
      below normal limits. Magnetic resonance imaging of the head revealed empty sella.
      A lumbar bone mineral density examination indicated severe osteoporosis. ESS
      caused a systemic hormone disorder in this patient, resulting in osteoporotic
      fractures and persistent non-fusion of the hand epiphyses. Possible causes of
      this anomaly are chronic or congenital abnormities of the pituitary gland. 

PMID- 24029022
TI  - Comparison between ultrasound-guided sciatic-femoral nerve block and unilateral
      spinal anaesthesia for outpatient knee arthroscopy.
AB  - OBJECTIVE: To compare unilateral spinal anaesthesia (USA) and ultrasound-guided
      combined sciatic-femoral nerve block (USFB) in ambulatory arthroscopic knee
      surgeries in terms of haemodynamic stability, nerve block quality, bladder
      function, adverse events and time-to-readiness for discharge (TRD). METHODS:
      Patients undergoing ambulatory arthroscopic knee surgery were randomly assigned
      to one of two groups. The USA group received 2 ml (10 mg) of 0.5% levobupivacaine
      and the USFB group received a 25 ml mixture consisting of 10 ml of 2.0%
      lidocaine, 10 ml of 0.5% levobupivacaine and 5 ml of saline (15 ml for the
      femoral and 10 ml for the sciatic nerve block). Preparation time (PT), surgical
      anaesthesia time (SAT), operation time, total anaesthesia time, time-to-first
      spontaneous urination, time-to-first analgesia, TRD, adverse events and patient
      satisfaction were recorded. RESULTS: A total of 40 patients were enrolled in the
      study (n = 20 per group). PT, SAT, total anaesthesia time and time-to-first
      analgesia were significantly shorter in the USA group than the USFB group; time
      to-first spontaneous urination and TRD were significantly longer in the USA group
      than the USFB group. CONCLUSIONS: USFB provided sufficient duration of sensory
      blockade and it reduced the TRD and the rate of adverse events.

PMID- 24029023
TI  - Respiratory morbidity of preterm infants of less than 33 weeks gestation without
      bronchopulmonary dysplasia: a 12-month follow-up of the CASTOR study cohort.
AB  - The aim of this study was to describe the incidence and risk factors for
      respiratory morbidity during the 12-month period following the first respiratory
      syncytial virus (RSV) season in 242 preterm infants [<33 weeks gestational age
      (GA)] without bronchopulmonary dysplasia and 201 full-term infants (39-41 weeks
      GA) from the French CASTOR study cohort. Preterm infants had increased
      respiratory morbidity during the follow-up period compared to full-terms; they
      were more likely to have wheezing (21% vs. 11%, P = 0.007) and recurrent wheezing
      episodes (4% vs. 1%, P = 0.049). The 17 infants (14 preterms, three full-terms)
      who had been hospitalized for RSV-confirmed bronchiolitis during their first RSV
      season had significantly more wheezing episodes during the follow-up period than
      subjects who had not been hospitalized for RSV-confirmed bronchiolitis (odds
      ratio 4.72, 95% confidence interval 1.71-13.08, P = 0.003). Male gender, birth
      weight <3330 g and hospitalization for RSV bronchiolitis during the infant's
      first RSV season were independent risk factors for the development of wheezing
      episodes during the subsequent 12-month follow-up period.

PMID- 24029024
TI  - Antifungal properties of gliadin films incorporating cinnamaldehyde and
      application in active food packaging of bread and cheese spread foodstuffs.
AB  - Gliadin films incorporating 1.5, 3 and 5% cinnamaldehyde (g/100g protein) were
      tested against food-spoilage fungi Penicillium expansum and Aspergillus niger in
      vitro, and were employed in an active food packaging system for sliced bread and
      cheese spread. Gliadin films incorporating cinnamaldehyde were highly effective
      against fungal growth. P. expansum and A. niger were completely inhibited after
      storage in vitro for 10 days in the presence of films incorporating 3%
      cinnamaldehyde. Indeed 1.5% cinnamaldehyde was sufficient in the case of P.
      expansum. The amount of cinnamaldehyde retained in films after storage for 45
      days at 20  degrees C and 0% RH was also sufficient in most cases to prevent
      fungal growth in vitro. Active food packaging with gliadin films incorporating 5%
      cinnamaldehyde increased the shelf-life of both sliced bread and cheese spread.
      Mold growth was observed on sliced bread after 27 days of storage at 23  degrees
      C with active packaging, whereas in the control bread packaged without the active
      film fungal growth appeared around the fourth day. In the cheese spread, no fungi
      were observed after 26 days of storage at 4  degrees C when the product was
      packaged with the active film. However, growth of fungi was observed in control
      packaged cheese after 16 days of storage. This work demonstrates a noteworthy
      potential of these novel bioplastics incorporating natural antimicrobial
      compounds as innovative solutions to be used in active food packaging to extend
      shelf-life of food products.

PMID- 24029025
TI  - Microbiological quality of selected street food items vended by school-based
      street food vendors in Dhaka, Bangladesh.
AB  - A cross sectional study was conducted to assess the microbiological quality of
      local food items vended by the school-based street food vendors in Dhaka City. A
      total of 80 schools from 19 school-zones of Dhaka City and its outskirts were
      chosen for the study. A total of 110 food samples, one each from 110 school-based
      street food vendors, were collected for laboratory analysis. Face to face
      interviews were conducted with the food vendors using a pre-tested questionnaire.
      The food samples were analyzed for coliform counts in the Public Health
      Laboratory, Institute of Public Health, Dhaka, which is a national level central
      food testing laboratory in Bangladesh. Microbiological criteria recommended by
      the International Commission on Microbiological Specifications for Foods (ICMSF)
      were considered to classify food samples as 'satisfactory' (total coliforms <100
      per g or ml) and 'unsatisfactory' (total coliforms >= 100 per g or ml).
      Multivariable logistic regression was used to explore the association of selected
      socio-demographic characteristics of school-based street food vendors with the
      presence of unsatisfactory levels of coliforms in their food items. Of the 110
      school-based street food samples analyzed in the laboratory, 44% were
      unsatisfactory. Among different items of street vended foods, 54% of sliced
      fruits samples, 59% of jhalmuri samples, 29% of chotpotis samples, 53% of
      vajavuji samples, and all (100%) sharbat samples were unsatisfactory, while all
      samples from achar (100%) and ice cream (100%) were found to be satisfactory.
      Logistic regression models showed that the food samples collected from the
      vendors belonging to the age group '15-24 years' and the vendors possessing an
      educational status higher than primary level were less likely to be
      unsatisfactory, while the food samples collected from the vendors having a daily
      income of more than 200 Bangladeshi Taka (equivalent to 3.00 USD) were more
      likely to be unsatisfactory. Our study findings reflected poor microbiological
      quality for a considerable proportion of the school-based street vended foods
      indicating a health threat to the school children of Dhaka City.

PMID- 24029026
TI  - Virus transfer proportions between gloved fingertips, soft berries, and lettuce,
      and associated health risks.
AB  - Multiple outbreaks of human norovirus (hNoV) have been associated with fresh
      produce, such as soft berries and lettuce. Even though food handlers are
      considered an important source for the introduction of hNoV into food chains,
      their contribution to public health risks associated with hNoV remains unknown.
      To assess to which extent food handlers contribute to the introduction and spread
      of hNoV in fresh produce chains quantitative virus transfer data are needed. We
      estimated transfer proportions of hNoV GI.4, GII.4, murine norovirus (MNV-1), a
      culturable surrogate of hNoV, and human adenovirus (hAdV-2), a human pathogen
      proposed as an indicator for human faecal pollution, between gloved fingertips
      and raspberries, strawberries, and lettuce, by quantitative RT-PCR and cell
      culture if applicable. Virus transfer proportions were corrected for virus-matrix
      specific recoveries, and variability and uncertainty of the parameters were
      estimated. Virus transfer from gloves to soft berries was generally lower as
      compared to lettuce, with mean transfer proportions ranging between 0.1 to 2.3%
      and 9 to 10% for infectious MNV-1 and hAdV-2, respectively. Transfer from produce
      to glove was mostly greater than transfer from glove to produce, adding to the
      likelihood of virus transfer due to cross contamination from contaminated produce
      via food handlers. HNoV GI.4 and hNoV GII.4 showed no significant difference
      between their mean transfer proportions. Using the estimated transfer
      proportions, we studied the impact of low and high transfer proportions on the
      public health risk, based on a scenario in which a food handler picked
      raspberries with contaminated fingertips. Given the made assumptions, we could
      show that for a pathogen as infectious as hNoV, low transfer proportions may pose
      a greater public health risk than high transfer proportions, due to a greater
      viral spread. We demonstrated the potential of food handlers in spreading hNoV in
      food chains, showing that prevention of virus contamination on food handlers'
      hands is crucial for food safety. Nevertheless, complete prevention of virus
      contamination on fresh produce cannot be achieved in reality, and reliable and
      effective intervention measures are consequently required. We estimated that,
      especially for low transfer proportions, a robust one log10-unit reduction of
      infectious hNoV on contaminated produce, and on food handlers' hands, could lower
      the public health risk substantially. Using the obtained data in quantitative
      risk assessment will aid in elucidating the contribution of food handlers in hNoV
      transmission. 

PMID- 24029027
TI  - Fermentation characteristics of yeasts isolated from traditionally fermented
      masau (Ziziphus mauritiana) fruits.
AB  - Yeast strains were characterized to select potential starter cultures for the
      production of masau fermented beverages. The yeast species originally isolated
      from Ziziphus mauritiana (masau) fruits and their traditionally fermented fruit
      pulp in Zimbabwe were examined for their ability to ferment glucose and fructose
      using standard broth under aerated and non-aerated conditions. Most Saccharomyces
      cerevisiae strains were superior to other species in ethanol production. The best
      ethanol producing S. cerevisiae strains, and strains of the species Pichia
      kudriavzevii, Pichia fabianii and Saccharomycopsis fibuligera were tested for
      production of flavor compounds during fermentation of masau fruit juice.
      Significant differences in the production of ethanol and other volatile compounds
      during fermentation of masau juice were observed among and within the four tested
      species. Alcohols and esters were the major volatiles detected in the fermented
      juice. Trace amounts of organic acids and carbonyl compounds were detected. Ethyl
      hexanoate and ethyl octanoate were produced in highest amounts as compared to the
      other volatile compounds. S. cerevisiae strains produced higher amounts of
      ethanol and flavor compounds as compared to the other species, especially fatty
      acid ethyl esters that provide the major aroma impact of freshly fermented wines.
      The developed library of characteristics can help in the design of mixtures of
      strains to obtain a specific melange of product functionalities. 

PMID- 24029028
TI  - A quantitative microbiological exposure assessment model for Bacillus cereus in
      REPFEDs.
AB  - One of the pathogens of concern in refrigerated and processed foods of extended
      durability (REPFED) is psychrotrophic Bacillus cereus, because of its ability to
      survive pasteurisation and grow at low temperatures. In this study a quantitative
      microbiological exposure assessment (QMEA) of psychrotrophic B. cereus in REPFEDs
      is presented. The goal is to quantify (i) the prevalence and concentration of B.
      cereus during production and shelf life, (ii) the number of packages with
      potential emetic toxin formation and (iii) the impact of different processing
      steps and consumer behaviour on the exposure to B. cereus from REPFEDs. The QMEA
      comprises the entire production and distribution process, from raw materials over
      pasteurisation and up to the moment it is consumed or discarded. To model this
      process the modular process risk model (MPRM) was used (Nauta, 2002). The product
      life was divided into nine modules, each module corresponding to a basic process:
      (1) raw material contamination, (2) cross contamination during handling, (3)
      inactivation during preparation, (4) growth during intermediate storage, (5)
      partitioning of batches in portions, (6) mixing portions to create the product,
      (7) recontamination during assembly and packaging, (8) inactivation during
      pasteurisation and (9) growth during shelf life. Each of the modules was modelled
      and built using a combination of newly gathered and literature data, predictive
      models and expert opinions. Units (batch/portion/package) with a B. cereus
      concentration of 10(5)CFU/g or more were considered 'risky' units. Results show
      that the main drivers of variability and uncertainty are consumer behaviour,
      strain variability and modelling error. The prevalence of B. cereus in the final
      products is estimated at 48.6% (+/-0.01%) and the number of packs with too high
      B. cereus counts at the moment of consumption is estimated at 4750 packs per
      million (0.48%). Cold storage at retail and consumer level is vital in limiting
      the exposure. Four key points were identified (i) raw material contamination,
      (ii) recontamination during packaging, (iii) reduction during pasteurisation and
      cooking and (iv) cold storage at retail and consumer level. 

PMID- 24029029
TI  - Effects of acupuncture on the symptoms of anxiety and depression caused by
      premenstrual dysphoric disorder.
AB  - OBJECTIVE: The objective of this investigation was to evaluate the effects of
      acupuncture and sham acupuncture on the symptoms of anxiety and depression
      brought on by premenstrual dysphoric disorder (PMDD). METHODS: In a single-blind
      randomised clinical trial, 30 volunteers with PMDD were assigned alternately to
      group 1 (acupuncture) or group 2 (sham acupuncture), and completed an evaluation
      of symptoms of anxiety and depression using the Hamilton Anxiety (HAM-A) and
      Hamilton Depression (HAM-D) Rating Scales. The procedure was performed twice a
      week for two menstrual cycles, for a total of 16 attendances for each
      participant. RESULTS: Before the intervention the mean HAM-A and HAM-D scores did
      not differ between groups. Following the intervention symptoms of anxiety and
      depression were reduced in both groups; however, the improvement was significant
      in group 1 compared to group 2, as shown by a mean reduction in HAM-A scores of
      58.9% in group 1 and 21.2% in group 2 (p<0.001). The reduction in the mean HAM-D
      scores was 52.0% in group 1 and 19.6% in group 2, resulting in a significant
      difference (p=0.012). CONCLUSIONS: The results suggest that acupuncture could be
      another treatment option for PMDD patients.

PMID- 24029030
TI  - A high incidence of adjacent-1 meiotic segregation pattern, revealed by
      multicolor sperm FISH, in a carrier boar of a new reciprocal translocation
      t(6;16)(p13;q23).
AB  - Reciprocal translocations pose a serious problem in pig breeding due to the
      reduced fertility of the carriers. This paper presents a new reciprocal
      translocation in a phenotypically normal, but hypoprolific (20% reduction) boar.
      Chromosome banding as well as the FISH technique with the use of BAC and
      telomeric probes was applied for a detailed characterization of this chromosome
      rearrangement. The karyotype of the studied boar was described as
      38,XY,t(6;16)(p13;q23). The meiotic segregation of the quadrivalent was studied
      in 1,071 sperms by multicolor FISH. The most frequent segregation patterns were
      alternate (47.5%) and adjacent 1 (41.9%), while adjacent 2 and 3:1 were less
      frequent at 1.2 and 9.2%, respectively. Surprisingly, the frequency of the
      adjacent-1 segregation appeared to be relatively high, when compared with human
      and pig reciprocal translocations studied by sperm FISH. Our study, along with a
      review of the literature, shows that a reduction of fertility in the carriers and
      the incidence of different segregation patterns of the quadrivalent may vary
      within a broad range, and both aspects seem to be unrelated. A need for
      obligatory karyotype screening programs of artificial insemination boars is
      emphasized.

PMID- 24029031
TI  - Influenza A H1N1 Related Acute Necrotizing Encephalopathy: Radiological Findings
      in Adulthood.
AB  - In 2009 a novel swine-origin Influenza A H1N1 virus was identified in Mexico and
      Southern California. Since it was first recognized, neurological complications
      including acute necrotizing encephalopathy (ANE) have been globally documented in
      association with this viral infection. ANE is mostly known to occur in the
      paediatric population. We describe a fatal case of ANE in a previously healthy 40
      year-old man infected with influenza A H1N1 virus presenting with severe
      neurologic decline. Computed tomography (CT) scan and magnetic resonance imaging
      (MRI) findings were consistent with ANE. CT and MR findings typically documented
      in paediatric cases of ANE - including bilateral thalamic necrosis with petechial
      hemorrhage - have been seldom described in adulthood. 

PMID- 24029032
TI  - Sickle cell disease in children: accuracy of imaging transcranial Doppler
      ultrasonography in detection of intracranial arterial stenosis.
AB  - This study aimed to determine the accuracy of imaging transcranial Doppler
      sonography in detection of intracranial arterial stenosis in children with sickle
      cell disease using three-dimensional MR angiography as a reference standard.
      Sixty-one children (mean age 102+/-39 months, 30 males), who had no history of
      overt stroke, and were classified as at lowest risk of stroke by mean flow
      velocity criterion <170 cm/s, underwent conventional and imaging transcranial
      Doppler ultrasonographic examinations. We employed the area under the receiver
      operating characteristic curve (AUC) to determine the accuracy of flow velocity
      measurements obtained with imaging ultrasonography with and without correction
      for the angle of insonation as well as with conventional ultrasonography. We also
      established the most efficacious velocity thresholds for detection of the
      stenosis. We found ten intracranial stenoses in six patients on MR angiography,
      but we calculated AUC only for detection of stenosis (n=6) of the left
      intracranial internal carotid artery. The accuracy of flow velocity with angle
      correction was lower than the accuracy of velocity without angle correction
      (AUC=0.73, 95% CI, 0.53-0.93 versus AUC=0.87, 95% CI, 0.74-1.00; p=0.017). The
      accuracy of flow velocity obtained with conventional ultrasonography (AUC=0.82,
      95% CI, 0.67-0.97) was not different from the accuracy of flow velocities
      obtained with imaging ultrasonography. We found that the threshold of 165 cm/s of
      mean velocity without angle correction is associated with highest efficiency for
      imaging (92%) and conventional ultrasonography (90%). Velocity measurements
      without angle-correction provide good accuracy in detection of stenosis of the
      terminal internal carotid artery, whereas angle-corrected velocities have lower
      accuracy. 

PMID- 24029033
TI  - Cerebral fat embolism detection with susceptibility-weighted images in sickle
      cell disease.
AB  - Cerebral fat embolism is a known but feared complication of sickle cell disease,
      which leads to significant morbidity. Although trauma-related fat embolism is
      more frequent and its diagnosis is straightforward, fat embolism secondary to
      bone infarcts after vaso-occlusive events can be unrecognized. Lack of criteria
      make the clinical diagnosis of sickle cell disease related fat embolism
      challenging. The neuroimaging findings are helpful to support the clinical
      diagnosis. Magnetic resonance imaging findings of fat embolism have been
      described including those seen on susceptibility-weighted imaging. Even though
      susceptibility-weighted imaging has been used for the diagnosis of cerebral fat
      embolism due to trauma, to the best of our knowledge its use has not been
      described in patients with sickle cell disease. We report an uncommon case of a
      60-year-old woman with sickle cell disease who developed cerebral fat embolism
      and in which the findings on susceptibility-weighted imaging were characteristic
      and established the diagnosis. 

PMID- 24029034
TI  - Giant dilatations of virchow-robin spaces in the midbrain. MRI aspects and review
      of the literature.
AB  - Virchow-Robin spaces are lesions often seen in the brain parenchyma but their
      etiopathogenesis remains unsettled. Giant Virchow-Robin spaces placed in the
      midbrain are extremely rare. We describe three patients with a diagnosis of giant
      Virchow-Robin spaces in the midbrain, and their clinical and radiologic findings.
      We reviewed the literature in terms of the etiopathology, anatomic and radiologic
      appearance and differential diagnosis of the giant Virchow-Robin spaces. The
      diagno-stic role of the high Tesla magnetic resonance devices and new sequences
      techniques such as three dimensional isotropic acquisition and diffusion tensor
      imaging were also evaluated in this case series. 

PMID- 24029035
TI  - Multiple intracranial meningiomas and cavernous hemangiomas.
AB  - Intracerebral meningiomas and cavernous hemangiomas (hemangiomas, cavernomas) are
      entities frequently encountered by neuroradiologists and neurosurgeons. Even
      multiple tumors can often be observed in patients with certain congenital
      conditions, eg. multiple meningiomas in neurofibromatosis type 2 or multiple
      cavernous hemangiomas in familial cavernous malformations. However, there are
      only very few reported cases of concurrent meningiomas and cavernous hemangiomas,
      all but one related to prior radiotherapy. We describe the second case of
      concurrent multiple meningiomas and cavernous hemangiomas occurring de novo
      without a history of radiation. 

PMID- 24029036
TI  - Intracranial calcifications. A pictorial review.
AB  - Brain calcifications are a common radiographic finding. The pathogenesis is
      diverse and ranges from benign physiological calcifications to a variety of
      pathological disorders. Whereas certain calcifications are considered an
      incidental finding, their presence can sometimes be crucial in making a specific
      diagnosis. Several pathological conditions affecting the brain parenchyma are
      associated with calcifications and their recognition and location might help in
      narrowing the differential. Knowledge of physiological calcifications is
      essential to avoid misinterpretation. This review illustrates a broad spectrum of
      CNS disorders associated with calcifications, and tries to highlight the salient
      radiological findings. 

PMID- 24029037
TI  - Calcifying Pseudoneoplasm of the Neuraxis. Two Case Reports and Review of CT and
      MR Findings.
AB  - Calcifying pseudoneoplasm is rarely encountered along the neuraxis, and only few
      cases have been reported to involve the spine. Its exact pathogenesis is unknown,
      and has been regarded as an unusual reactive process which must be differentiated
      from infection or malignancy. This rare entity carries a good prognosis after
      surgical resection. We report on the computed tomography and magnetic resonance
      imaging and diffusion-weighted features of calcifying pseudoneoplasm of the spine
      by describing two patients with involvement of the craniocervical junction, and
      thoracic spine. 

PMID- 24029038
TI  - Intraosseous tumors of the skull. A pictorial review.
AB  - Radiologists often encounter intraosseous tumors of the calvarium. Compared with
      parenchymal lesions, information is limited. In this review, we list the
      calvarial tumors and correlate the radiologic appearance with the pathologic
      findings. We discuss primary intraosseous tumors and tumor secondary to systemic
      disease as well as metastatic malignant tumor. Differentiation between primary
      tumors and tumors secondary to systemic disease can be difficult. Physicians
      should explore the systematic disease. In the case of primary tumors, it is
      important to verify any soft-tissue component since this is an important
      differential diagnostic feature with the potential for malignant transformation. 

PMID- 24029039
TI  - Endovascular treatment of intractable bleeding from a traumatic pseudoaneurysm of
      the internal maxillary artery.
AB  - Traumatic pseudoaneurysms of the internal maxillary artery (IMA) are rare and
      difficult to treat. A 58-year-old man with a traumatic pseudoaneurysm of the IMA
      presented with intractable nasal and oral hemorrhage during dual antiplatelet
      therapy. Transcatheter artery embolization with N-butyl cyanoacrylate (NBCA)
      completely occluded the pseudoaneurysm. Transcatheter artery embolization with
      NBCA is a feasible and effective treatment because of its shorter treatment time
      and lower incidence of recurrence. 

PMID- 24029040
TI  - Paget's Disease. A Case Report.
AB  - Paget's disease (PD) is a common focal progressive osteometabolic disorder
      characterised by a disturbance in bone modelling and remodelling, because of an
      increase in osteoblastic and osteoclastic activity. It is a condition of unknown
      aetiology affecting approximately 3% of the population over 40 years of age and,
      approximately 10% of those over the age of 85 years. It is most common in
      Northern Europe and Australia and is rare in Asia and Africa. We describe the
      case of a 71-year-old man diagnosed with PD confined to the sacrum. After
      laboratory test, an imaging study with radiography, scintigraphy, computed
      tomography (CT) and magnetic resonance imaging (MRI) was performed disclosing
      findings compatible with Paget's disease in middle pathologic phase. The
      diagnosis was confirmed at biopsy. The structural modification of the sacrum with
      spongiosa rarefaction, thickening of bone and intact bone cortical, confirmed by
      CT, are tipical of an intermediate phase of PD. This was also supported by signal
      MRI changes showing substitution of the red by the fat medulla, visualized by FS
      sequences. Once the treatment for the bone disease was established, the patient
      no longer complained of pain. Special attention should be paid to male and
      elderly patients with pain in the lumbar spine because of the potential risk
      cancer development (21). The radiologist must be attentive to the possible
      presentations and complications of PD, even in uncommon sites, trying whenever
      possible to correlate the radiological features with the patient's clinical
      symptoms. 

PMID- 24029041
TI  - Pulmonary embolism caused by cement leakage during percutaneous vertebroplasty. A
      case report of successful conservative management.
AB  - Percutaneous vertebroplasty (PV) is considered a minimally invasive procedure,
      yet cement leakage into the circulation may result in serious complications.
      Here, we are reporting a case of pulmonary embolism following PV for treatment of
      osteoporotic compression vertebral fracture. 

PMID- 24029042
TI  - Letter to the Editor. Congenital X-linked Stapes Gusher Syndrome.
AB  - X-Linked sensorineuronal hearing loss (SNHL) is a rare but recognized cause of
      bilateral SNHL associated with CSF gusher. We report a case presenting a varied
      imaging spectrum and clinical scenario of a one year old boy with unilateral
      profound hearing loss and recurrent meningitis due to spontaneous oval window
      gusher. Imaging showed a unilateral abnormality, with the fistula leaking from
      the oval window into the middle ear cleft. 

PMID- 24029043
TI  - A matched-cohort study of pediatric head injuries: collecting data to inform an
      evidence-based triage assessment.
AB  - Triage nurses are the "first stop" for patients who present to the emergency
      department for care. The assessment of pediatric head injuries is especially
      challenging because signs and symptoms of head trauma in children do not
      correlate well with the risk of closed head injury (CHI). METHODS: A
      retrospective matched cohort study was conducted to compare 2 groups of patients
      who presented to a pediatric emergency department for evaluation of a head
      injury: a CHI-positive cohort and a CHI-negative cohort as identified by computed
      tomography scan. The purpose of the chart review was to collect specific
      information from both cohorts which could be used to inform a nurse-driven
      pediatric head injury assessment tool. RESULTS: The younger the child, the more
      likely they were to be asymptomatic. Scalp hematomas in infants <3 months were
      associated with CHI even if the infants were otherwise asymptomatic. Injuries to
      the temporal-parietal region were associated with CHI at every age. Frequency of
      caregiver report of loss of consciousness (LOC) was almost identical in both
      cohorts. Children in every age category sustained CHIs as the result of minor
      falls based on standard age-related fall criteria. DISCUSSION: The infants and
      children at highest risk for CHI are often the most difficult to assess. The
      results of this study reinforce the need for a nurse-driven, evidence-based risk
      scoring system that could be used to aid with early identification of infants and
      children who are at high risk for CHI.

PMID- 24029044
TI  - Focus on forensic nursing education.

PMID- 24029046
TI  - Comparative study of the efficacy of allogeneic hematopoietic stem cell
      transplantation from human leukocyte antigen-haploidentical related and unrelated
      donors in the treatment of leukemia.
AB  - AIMS: To compare the efficacy of hematopoietic stem cell transplantation (HSCT)
      from human leukocyte antigen (HLA)-haploidentical related donors (RD) and
      unrelated donors (URD) in the treatment of leukemia. METHODS: Ninety-three
      leukemia patients underwent allogeneic HSCT were divided into two groups: 51
      cases of RD-HSCT and 42 cases of URD-HSCT. In the RD-HSCT group, a
      preconditioning regimen with fludarabine (Flu) + busulfan (Bu) + cytosine
      arabinoside (Ara-C) was used in 42 patients and total body irradiation (TBI) +
      Flu + Ara-C was used in the remaining 9. RESULTS: In the URD-HSCT group, a
      modified preconditioning regimen with Bu + cyclophosphamide was used in 35
      patients, while the other 7 patients underwent treatment with TBI + Flu. After
      transplantation, the occurrence rate of grade II-IV acute graft-versus-host
      disease (GVHD) was 46.0 and 51.2% in the two groups. Likewise, the rate of
      chronic GVHD was 46.0 and 63.4%, respectively. No significant differences in the
      occurrence of acute and chronic GVHD were detected between the two groups. The
      differences in early-stage infection rate after transplantation, recurrence rate,
      3-year survival rate, and disease-free survival rate between the two groups were
      not significant. CONCLUSION: HLA-haploidentical RD-HSCT with enhanced
      preconditioning and administration of immunosuppressants showed a clinical
      efficacy similar to that of URD-HSCT against leukemia, without the risk of
      increased infection and GVHD.

PMID- 24029045
TI  - Parental tobacco screening and counseling in the pediatric emergency department:
      practitioners' attitudes, perceived barriers, and suggestions for implementation
      and maintenance.
AB  - INTRODUCTION: The pediatric emergency department (PED) is a venue that underuses
      parental tobacco screening and brief cessation counseling. We sought to explore
      PED practitioners' attitudes and perceived barriers regarding the implementation
      and adoption of tobacco screening/cessation counseling of parental smokers in the
      PED setting, as well as to solicit suggestions for improving the sustainability
      and maintenance of such practices. METHODS: We conducted an exploratory,
      qualitative study of a convenience sample of PED practitioners using the RE-AIM
      (reach, effectiveness, adoption, implementation, and maintenance) framework.
      Individual, focused interviews were conducted to determine factors that would
      maximize the implementation and maintenance of parental tobacco screening and
      intervention counseling as standard PED practice. RESULTS: Thirty interviews were
      conducted from which relevant data, patterns, and themes were identified. Reach
      factors included targeting parental smokers with children with respiratory
      diseases, having adequate training of practitioners, and providing "prearranged"
      counseling packages. Effectiveness factors included practitioner desire for
      outcome data about intervention effectiveness (eg, changes in children's
      secondhand smoke exposure and parental quit rates). Solutions to increase
      intervention adoption included quick electronic health record prompts and the
      provision of onsite tobacco cessation experts. Implementation suggestions
      emphasized the importance of financial support and the alignment of tobacco
      screening/counseling with strategic plans. Maintenance factors included
      institutional and technical support, as well as the importance of intervention
      "champions" in the PED. DISCUSSION: By highlighting important viewpoints of
      practitioners regarding tobacco screening and counseling, the findings can help
      guide and direct the development and evaluation of sustainable interventions to
      facilitate tobacco use treatment in the PED.

PMID- 24029048
TI  - Real-time wireless compliance monitoring system using calendar-type pill
      organizer.
AB  - BACKGROUND: Accurate information about patients' use of medication is crucially
      important for medical treatment. Real-time information can prevent treatment
      failure resulting from medication delays or failures. OBJECTIVE: In this study, a
      compliance-monitoring system is developed for physicians to ascertain their
      patients' drug-taking behaviors at home in real time. Its operation is then
      evaluated. METHODS: The authors produced a device that uses wireless
      communication to notify a physician that drugs are taken out of a package by a
      patient. The device has sensors to detect the package opening. A wireless module
      is installed in a drug-containing calendar-type pill organizer. RESULTS:
      Experimental trials confirmed that a physician can monitor the kind and number of
      drugs removed from the package on a real-time basis. Furthermore, a practical
      system can be produced by measuring the distance and consumption current of the
      produced device, which allows wireless communication. CONCLUSIONS: This system
      enables a doctor to intervene immediately when any compliance lapse occurs,
      thereby preventing treatment failure caused by delayed response.

PMID- 24029049
TI  - Academic Radiology in 2020: articles based on the 2012 AUR Carestream Innovations
      in Academic Radiology Course.

PMID- 24029050
TI  - Balancing the three missions and the impact on academic radiology.
AB  - The three missions of academic radiology compete with one another for time and
      funding. Revenue for the clinical mission often subsidizes education and
      research. Given the internal and external drivers/pressures on health care and,
      more particularly, on academic health centers, the current model is
      unsustainable. Trends seen in other industries are entering academic health care.
      The radiology department of the future will need to be more efficient with
      increasingly fewer resources while meeting its missions at higher levels of
      expectation. 

PMID- 24029052
TI  - Impact of Patient Protection and Affordable Care Act on academic radiology
      departments' clinical, research, and education missions.
AB  - The Patient Protection and Affordable Care Act (ACA) generated significant media
      attention since its inception. When the law was approved in 2010, the U.S. health
      care system began facing multiple changes to adapt and to incorporate measures to
      meet the new requirements. These mandatory changes will be challenging for
      academic radiology departments (ARDs) since they will need to promote a shift
      from a volume-focused to a value-focused practice. This will affect all
      components of the mission of ARDs, including clinical practice, education, and
      research. A unique key element to success in this transition is to focus on both
      quality and safety, thus improving the value of radiology in the post-ACA era.
      Given the changes ARDs will face during the implementation of ACA, suggestions
      are provided on how to adapt ARDs to this new environment. 

PMID- 24029051
TI  - Imaging informatics: essential tools for the delivery of imaging services.
AB  - There are rapid changes occurring in the health care environment. Radiologists
      face new challenges but also new opportunities. The purpose of this report is to
      review how new informatics tools and developments can help the radiologist
      respond to the drive for safety, quality, and efficiency. These tools will be of
      assistance in conducting research and education. They not only provide greater
      efficiency in traditional operations but also open new pathways for the delivery
      of new services and imaging technologies. Our future as a specialty is dependent
      on integrating these informatics solutions into our daily practice. 

PMID- 24029053
TI  - The significance of alteration 2-[fluorine-18]fluoro-2-deoxy-(D)-glucose uptake
      in the liver and skeletal muscles of patients with hyperthyroidism.
AB  - RATIONALE AND OBJECTIVES: Hyperthyroidism leads to an enhanced demand for
      glucose. The hypothesis of the study is that 2-[fluorine-18]fluoro-2-deoxy-d
      glucose (FDG) positron emission tomography (PET) can demonstrate the alteration
      of systemic glucose metabolism in hyperthyroidism patients by measuring the FDG
      standard uptake value (SUV) in liver and skeletal muscle. MATERIALS AND METHODS:
      Forty-eight active hyperthyroidism patients and 30 control participants were
      recruited for the study. The intensity of FDG uptake in the liver and thigh
      muscles was graded subjectively, comprising three groups: group I, higher FDG
      uptake in the liver; group II, equal FDG uptake in the liver and muscles; and
      group III, higher FDG uptake in the muscles. Ten subjects with FDG PET scans at
      hyperthyroid and euthyroid status were analyzed. Serum levels of thyroxine (T4)
      and triiodothyronine (T3) correlated to the SUVs of the liver and muscles.
      RESULTS: Forty-one patients (41/48, 85.4%) showed symmetrically increased FDG
      uptake in the muscles (22 in group I, 9 in group II, and 17 in group III). Group
      I patients were significantly older than group II (P = .02) and group III (P =
      .001) patients. The correlation coefficient between the serum T3, T4, and SUV
      levels in the muscles was significant (r = 0.47-0.77, P < .01), particularly in
      liver and muscle FDG uptake between hyperthyroid and euthyroid states. In the 30
      control subjects, there was normal physiological FDG uptake in the liver and
      muscles. CONCLUSION: In PET scans showing a pattern of decreased liver and
      increased skeletal muscle FDG uptake in hyperthyroidism patients, this change of
      FDG distribution is correspondence to the severity of hyperthyroidism status.

PMID- 24029054
TI  - Regional alveolar partial pressure of oxygen measurement with parallel
      accelerated hyperpolarized gas MRI.
AB  - RATIONALE AND OBJECTIVES: Alveolar oxygen tension (Pao2) is sensitive to the
      interplay between local ventilation, perfusion, and alveolar-capillary membrane
      permeability, and thus reflects physiologic heterogeneity of healthy and diseased
      lung function. Several hyperpolarized helium ((3)He) magnetic resonance imaging
      (MRI)-based Pao2 mapping techniques have been reported, and considerable effort
      has gone toward reducing Pao2 measurement error. We present a new Pao2 imaging
      scheme, using parallel accelerated MRI, which significantly reduces measurement
      error. MATERIALS AND METHODS: The proposed Pao2 mapping scheme was computer
      simulated and was tested on both phantoms and five human subjects. Where
      possible, correspondence between actual local oxygen concentration and derived
      values was assessed for both bias (deviation from the true mean) and imaging
      artifact (deviation from the true spatial distribution). RESULTS: Phantom
      experiments demonstrated a significantly reduced coefficient of variation using
      the accelerated scheme. Simulation results support this observation and predict
      that correspondence between the true spatial distribution and the derived map is
      always superior using the accelerated scheme, although the improvement becomes
      less significant as the signal-to-noise ratio increases. Paired measurements in
      the human subjects, comparing accelerated and fully sampled schemes, show a
      reduced Pao2 distribution width for 41 of 46 slices. CONCLUSION: In contrast to
      proton MRI, acceleration of hyperpolarized imaging has no signal-to-noise
      penalty; its use in Pao2 measurement is therefore always beneficial. Comparison
      of multiple schemes shows that the benefit arises from a longer time-base during
      which oxygen-induced depolarization modifies the signal strength. Demonstration
      of the accelerated technique in human studies shows the feasibility of the method
      and suggests that measurement error is reduced here as well, particularly at low
      signal-to-noise levels.

PMID- 24029055
TI  - Effect of high-pitch dual-source CT to compensate motion artifacts: a phantom
      study.
AB  - RATIONALE AND OBJECTIVES: To evaluate the potential of high-pitch, dual-source
      computed tomography (DSCT) for compensation of motion artifacts. MATERIALS AND
      METHODS: Motion artifacts were created using a moving chest/cardiac phantom with
      integrated stents at different velocities (from 0 to 4-6 cm/s) parallel (z
      direction), transverse (x direction), and diagonal (x and z direction combined)
      to the scanning direction using standard-pitch (SP) (pitch = 1) and high-pitch
      (HP) (pitch = 3.2) 128-detector DSCT (Siemens, Healthcare, Forchheim, Germany).
      The scanning parameters were (SP/HP): tube voltage, 120 kV/120 kV; effective tube
      current time product, 300 mAs/500 mAs; and a pitch of 1/3.2. Motion artifacts
      were analyzed in terms of subjective image quality and object distortion. Image
      quality was rated by two blinded, independent observers using a 4-point scoring
      system (1, excellent; 2, good with minor object distortion or blurring; 3,
      diagnostically partially not acceptable; and 4, diagnostically not acceptable
      image quality). Object distortion was assessed by the measured changes of the
      object's outer diameter (x) and length (z) and a corresponding calculated
      distortion vector (d) (d = ?(x(2) + z(2))). RESULTS: The interobserver agreement
      was excellent (k = 0.91). Image quality using SP was diagnostically not
      acceptable with any motion in x direction (scores 3 and 4), in contrast to HP
      DSCT where it remained diagnostic up to 2 cm/s (scores 1 and 2). For motion in
      the z direction only, image quality remained diagnostic for SP and HP DSCT
      (scores 1 and 2). Changes of the object's diameter (x), length (z), and
      distortion vectors (d) were significantly greater with SP (overall: x = 1.9 cm +/
      1.7 cm, z = 0.6 cm +/- 0.8 cm, and d = 1.4 cm +/- 1.5 cm) compared to HP DSCT
      (overall: x = 0.1 cm +/- 0.1 cm, z = 0.0 cm +/- 0.1 cm, and d = 0.1 cm +/- 0.1
      cm; each P < .05). CONCLUSION: High-pitch DSCT significantly decreases motion
      artifacts in various directions and improves image quality.

PMID- 24029056
TI  - A comparative analysis of water-soluble and blood-pool contrast agents for in
      vivo vascular imaging with micro-CT.
AB  - RATIONALE AND OBJECTIVES: In recent years, micro-computed tomography (micro-CT)
      has emerged as a high-resolution modality for vascular exploration in vivo.
      Several x-ray contrast agents for in vivo imaging are on the market and are based
      on different formulations. The objective of this study was to compare contrast
      related and pharmacokinetic properties of a water-soluble compound containing
      iomeprol (Iomeron 400) and blood-pool agents (eXIA160XL, AuroVist 15 nm, and
      ExiTron nano 12000) for the identification of suitable in vivo vascular imaging
      applications. MATERIALS AND METHODS: Forty-four healthy C57BL/6J mice were used
      in this study. Iomeprol was administered with a continuous infusion protocol; the
      other agents as a bolus. Anatomical micro-CT was applied at the head, neck, and
      lower hind limb before (baseline) and immediately after contrast injection, and
      used to quantify contrast-related properties of the agents. Dynamic micro-CT was
      applied at the same regions to characterize the agents pharmacokinetics. RESULTS:
      All contrast media revealed safe, except for eXIA160XL, which caused death in
      four of eight tested animals and was therefore excluded early from the study.
      AuroVist 15 nm provided the highest attenuation (2.33/mm) as compared to iomeprol
      (1.97/mm) and ExiTron nano 12000 (1.58/mm) and a maximum temporal variation of
      contrast of 20% after 30 minutes, but the appearance of a dark skin staining did
      not allow multiple injections of the agent. Iomeprol passively diffused across
      capillary membranes, and after 30 minutes doubled the tissue contrast with
      respect to its initial levels. ExiTron nano 12000 revealed temporal variations of
      contrast below 10% and significantly reduced clearance rates after the third
      consecutive injection. CONCLUSION: AuroVist 15 nm is best suited for anatomical
      investigation of the vascular network, while the high extravasation levels of
      iomeprol can be exploited for perfusion analysis. ExiTron nano 12000 is indicated
      for use in longitudinal monitoring with repeated injections.

PMID- 24029057
TI  - Evaluation of a novel macromolecular cascade-polymer contrast medium for dynamic
      contrast-enhanced MRI monitoring of antiangiogenic bevacizumab therapy in a human
      melanoma model.
AB  - RATIONALE AND OBJECTIVES: To assess the applicability of a novel macromolecular
      polyethylene glycol (PEG)-core gadolinium contrast agent for monitoring early
      antiangiogenic effects of bevacizumab using dynamic contrast-enhanced (DCE)
      magnetic resonance imaging (MRI). MATERIALS AND METHODS: Athymic rats (n = 26)
      implanted with subcutaneous human melanoma xenografts underwent DCE-MRI at 2.0 T
      using two different macromolecular contrast agents. The PEG core cascade polymer
      PEG12,000-Gen4-(Gd-DOTA)16, designed for clinical development, was compared to
      the prototype, animal-only, macromolecular contrast medium (MMCM) albumin-(Gd
      DTPA)35. The treatment (n = 13) and control (n = 13) group was imaged at baseline
      and 24 hours after a single dose of bevacizumab (1 mg) or saline to
      quantitatively assess the endothelial-surface permeability constant (K(PS),
      MUL?min?100 cm(3)) and the fractional plasma volume (fPV,%), using a two
      compartment kinetic model. RESULTS: Mean K(PS) values, assessed with PEG12,000
      Gen4-(Gd-DOTA)16, declined significantly (P < .05) from 29.5 +/- 10 MUL?min?100
      cm(3) to 10.4 +/- 7.8 MUL?min?100 cm(3) by 24 hours after a single dose of
      bevacizumab. In parallel, K(PS) values quantified using the prototype MMCM
      albumin-(Gd-DTPA)35 showed an analogous, significant decline (P < .05) in the
      therapy group. No significant effects were detected on tumor vascularity or on
      microcirculatory parameters in the control group between the baseline and the
      follow-up scan at 24 hours. CONCLUSION: DCE-MRI enhanced with the novel MMCM
      PEG12,000-Gen4-(Gd-DOTA)16 was able to monitor the effects of bevacizumab on
      melanoma xenografts within 24 hours of a single application, validated by the
      prototype, animal-only albumin-(Gd-DTPA)35. PEG12,000-Gen4-(Gd-DOTA)16 may be a
      promising candidate for further clinical development as a macromolecular blood
      pool contrast MRI agent.

PMID- 24029058
TI  - Detecting radiation-induced injury using rapid 3D variogram analysis of CT images
      of rat lungs.
AB  - RATIONALE AND OBJECTIVES: To investigate the ability of variogram analysis of
      octree-decomposed computed tomography (CT) images and volume change maps to
      detect radiation-induced damage in rat lungs. MATERIALS AND METHODS: The lungs of
      female Sprague-Dawley rats were exposed to one of five absorbed doses (0, 6, 9,
      12, or 15 Gy) of gamma radiation from a Co-60 source. At 6 months postexposure,
      pulmonary function tests were performed and four-dimensional (4D) CT images were
      acquired using a respiratory-gated microCT scanner. Volume change maps were then
      calculated from the 4DCT images. Octree decomposition was performed on CT images
      and volume change maps, and variogram analysis was applied to the decomposed
      images. Correlations of measured parameters with dose were evaluated. RESULTS:
      The effects of irradiation were not detectable from measured parameters,
      indicating only mild lung damage. Additionally, there were no significant
      correlations of pulmonary function results or CT densitometry with radiation
      dose. However, the variogram analysis did detect a significant correlation with
      dose in both the CT images (r = -0.57, P = .003) and the volume change maps (r = 
      0.53, P = .008). CONCLUSION: This is the first study to use variogram analysis of
      lung images to assess pulmonary damage in a model of radiation injury. Results
      show that this approach is more sensitive to detecting radiation damage than
      conventional measures such as pulmonary function tests or CT densitometry.

PMID- 24029059
TI  - Online training on the safe use of fluoroscopy can result in a significant
      decrease in patient dose.
AB  - RATIONALE AND OBJECTIVES: Concerns over medical radiation exposure have received
      national press in recent years, and training in the appropriate use of radiation
      has become an essential component of every radiology residency program.
      Appropriate training is particularly important in fluoroscopy because it is
      commonly used by inexperienced radiology residents and has the potential to
      impart relatively high patient radiation doses. In an effort to minimize the
      radiation doses received by patients, our institution has recently initiated an
      online training program in the safe use of fluoroscopy. This course is required
      and must be completed by new radiology residents before their first fluoroscopy
      rotation. The goal of this study was to determine if the use of an online course
      in the safe use of fluoroscopy could result in decreased patient dose without
      affecting diagnostic quality. MATERIALS AND METHODS: Four years of retrospective
      procedural data for residents performing gastrointestinal and genitourinary
      fluoroscopic procedures without specialized training were reviewed. Incoming
      residents took an American Medical Association-accredited online training program
      in the safe use of fluoroscopy the week before their first fluoroscopy rotation.
      Patient dose and diagnostic quality data, inferred from the frequency of
      attending physician intervention necessary to complete the procedure, were
      collected for all exams performed by the new group of residents after completion
      of the training course. This was then compared to data from prior classes and
      stratified by procedure type. RESULTS: Statistically significant reductions in
      both average fluoroscopy time (FT) or dose-area-product (DAP) were found for many
      of the fluoroscopic procedures performed by residents who participated in the
      online fluoroscopy training program. Specifically, statistically significant
      reductions in FT for barium enema, cystogram, defecogram, and esophagram
      procedures (P < .001) were found. Esophagram and upper gastrointestinal studies
      were completed with a significantly lower DAP (P < .001). The average reduction
      in DAP across all procedures performed by first-year residents was 38%, whereas
      the average reduction in FT was 25%. Based on a review of data from all
      procedures performed, there was no statistically significant loss in diagnostic
      quality. CONCLUSION: An online training program can be effectively used to
      provide radiation safety instruction immediately before the start of a resident's
      fluoroscopy rotation, decreasing patient dose without affecting diagnostic
      quality.

PMID- 24029060
TI  - The role of ultrasonography in the evaluation of abdominal fat: analysis of
      technical and methodological issues.
AB  - RATIONALE AND OBJECTIVES: Ultrasonography (US) is becoming popular for the
      assessment of adiposity, but no one has studied this tool in the light of its
      potential limitations. Our purpose was to investigate the impact of technical
      conditions on the evaluation of abdominal fat by US. MATERIALS AND METHODS: Forty
      five healthy males and 45 healthy females were consecutively enrolled in the
      study, randomly assigned to three groups equally distributed by sex, and examined
      accordingly to three technical points: fasting state (before and after meal [A]),
      breathing (expiration and inspiration [B]), and US equipment from different
      generations: 2003 and 1998 (C). Two blinded radiologists performed US in the
      these opposite conditions, acquiring five parameters representative of
      subcutaneous and visceral adiposity in two times. Student's t-test and Lin's
      correlation coefficient were used for statistical analysis to assess differences
      in the measures as well as in inter- and intra-observer agreements. RESULTS: The
      maximum and the only statistically significant changes were observed for intra
      abdominal fat thickness regarding fasting state and breathing (Delta% = 24.1 +/-
      21.3 and Delta% = 9.2 +/- 20.4, respectively; P < .0001). Reproducibility and
      repeatability, especially for visceral fat, were proved more stable in the
      following conditions: fasting state, expiration, and newer machine (2003).
      CONCLUSION: This article provides essential information and "range of confidence"
      for variations that can be expected from using different conditions in the
      measurement of abdominal adiposity by US to be carefully addressed as well as
      considered by US users and by researchers involving this technique in the field
      of body composition.

PMID- 24029062
TI  - Removal of comfort pads underneath babies: a method of reducing radiation
      exposure to neonates.
AB  - RATIONALE AND OBJECTIVES: The recent increasing utilization of imaging has
      increased the population exposure to ionizing radiation. With increasing
      knowledge of the potential harm of radiation exposure, efforts should be made to
      minimize patient radiation whenever possible, especially in young children. The
      purpose of this study was to use the exposure index (EI) standard to assess the
      potential for reducing radiation dose to babies by removing a soft comfort pad,
      often placed underneath the baby. The pad is located between the baby and the
      image detector plate. As such it absorbs x-rays that have already passed through
      the baby but have not yet reached the imaging detector plate. MATERIALS AND
      METHODS: Using a thoracic infant phantom and fixed exposure factors, we measured
      the percentage of the radiation exiting a neonatal chest phantom that was
      absorbed/attenuated by the comfort pad, before it hit the detector to create the
      image. We studied comfort pads of 4 different thicknesses, ranging from 0.5" to
      8". RESULTS: Radiation beam attenuation, ranging from 12% to 72.1%, was found
      with all comfort pads, with increased x-ray beam attenuation occurring with
      increasing pad thickness. CONCLUSIONS: The study shows that comfort pads cause a
      high attenuation of the radiation beam, after it exits the chest phantom. As
      such, removal of the pads prior to radiographic exposure of babies is a method of
      potentially reducing patient radiation exposure in the newborn nursery.

PMID- 24029061
TI  - Reduced Insular Glutamine and N-acetylaspartate in systemic lupus erythematosus:
      a single-voxel (1)H-MR spectroscopy study.
AB  - RATIONALE AND OBJECTIVES: To investigate for differences in metabolic
      concentrations and ratios between patients with systemic lupus erythematosus
      (SLE) without (group SLE) and those with neurological symptoms (group NPSLE)
      compared to a healthy control (group HC) in three normal-appearing brain regions:
      the frontal white matter, right insula (RI), and occipital gray matter and
      whether changes in any of the metabolites or metabolic ratios are correlated to
      disease activity and other clinical parameters. MATERIALS AND METHODS: Twenty
      patients with SLE (18 women and 2 men, age range 23.4-64.6 years, mean age 43.9
      years), 23 NPSLE patients (23 women, age range 23.7-69.8 years, mean age 42.4
      years), and 21 HC (19 women and 2 men, age range 21.0-65.7 years, mean age 43.4
      years) were included. All subjects had conventional brain magnetic resonance
      imaging and (1)H single-voxel spectroscopy, clinical assessment, and laboratory
      testing. RESULTS: NPSLE patients had significantly reduced N-acetylaspartate
      (NAA)/creatine compared to HC (P = .02) and SLE patients (P = .01) in the RI.
      Lower glutamine/creatine levels were also detected in RI in both patient groups
      and in frontal white matter in NPSLE patients compared to HC (P = .01, P = .02).
      NAA/Cr ratio in the RI was significantly negatively correlated with the Systemic
      Lupus Erythematosus Disease Activity Index (r = -0.41; P = .008), and patients
      with active SLE symptoms also had a trend toward lower NAA/creatine ratios (1.02
      vs 1.12; P = .07). CONCLUSIONS: The present data support previous findings of
      abnormal metabolic changes in normal-appearing regions in the brain of both SLE
      and NPSLE patients and raise the possibility that especially NAA, glutamine, and
      glutamate may be additional biomarkers for cerebral disease activity in SLE
      patients as these early metabolic changes occur in the brain of SLE patients
      before neurologic and imaging manifestations become apparent.

PMID- 24029063
TI  - A novel analysis algorithm for potential quantitative assessment of myocardial
      computed tomography perfusion.
AB  - RATIONALE AND OBJECTIVES: Cardiac computed tomography (CT) has emerged as a
      robust modality for imaging coronary stenosis and has recently been used to
      evaluate myocardial abnormalities such as ischemic perfusion defects and
      infarction. We developed a new image analysis algorithm for the semiautomatic and
      quantitative assessment of myocardial perfusion by CT. MATERIALS AND METHODS: The
      algorithm semiautomatically segments two-dimensional short-axis reformatted DICOM
      images of the left ventricle into regions of interest (ROIs) in accordance with
      American Heart Association (AHA) standards and is capable of creating nine
      further ROI subsegments. This includes separate endocardial, mid-ventricle, and
      epicardial layers. Image intensity values (Hounsfield unit) and relative
      myocardial thickness are quantitatively reported for each ROI and segment.
      RESULTS: The algorithm allows comparison of the HU values at the same ROI
      locations between rest and stress. The reproducibility is very good; ICC 0.89 for
      rest images, 0.83 for stress images. The mean time for generating ROIs for the
      entire heart was 11 minutes versus 22 minutes for manual tracing. CONCLUSION: The
      algorithm reports parameters relevant for evaluation of stress perfusion CT
      studies and will allow more accurate and reproducible analysis in cardiac CT
      research.

PMID- 24029064
TI  - Implementation and outcomes of a resident-led physics curriculum with integration
      of the RSNA/AAPM physics modules.
AB  - RATIONALE AND OBJECTIVES: With the impending integration of clinically relevant
      physics into the new American Board of Radiology Core exam, diagnostic radiology
      residency programs are faced with the challenge of how best to adapt the teaching
      of radiologic physics to residents. We present a novel resident-led physics
      curriculum that replaces the traditional didactic structure used in previous
      years. The hypothesis is that a self-teaching curriculum will facilitate greater
      retention of core physics concepts and foster a mentality of independent
      learning. We present both the implementation of this new curriculum and the
      initial outcomes. MATERIALS AND METHODS: A 2-year resident-led physics curriculum
      was designed and implemented, with integration of the Radiological Society of
      North America/American Association of Physicists in Medicine online Physics
      Modules. A preimplementation survey was completed by residents to assess opinions
      on the previous lecture-based didactic curriculum. A postimplementation survey
      was then administered six months into the new resident-led curriculum. DXIT
      Physics percentile scores were compared before and after the curriculum change.
      The outcomes analysis of this study was approved by the University of Pittsburgh
      Institutional Review Board and issued IRB approval #PRO13050022. RESULTS: Average
      Physics DXIT percentile scores improved by 24.1% after the implementation of the
      resident-led curriculum. Results from the postimplementation survey reveal that
      36% of residents think the change was a "Significant Improvement" in physics
      education. Also, 50% of responses have rated the new curriculum as "Moderately"
      effective, and an additional 13% of responses have rated the curriculum as "Very
      to-Extremely" effective in teaching physics. CONCLUSIONS: Compared to our prior
      lecture-based physics curriculum, the change to a resident-led physics
      curriculum, to teach clinically relevant physics concepts to radiology residents,
      has been both effective and well received.

PMID- 24029065
TI  - Making education effective and fun: stations-based approach to teaching radiology
      and anatomy to third-year medical students.
AB  - RATIONALE AND OBJECTIVES: A hands-on stations-based approach to teaching anatomy
      to third-year medical students is used at Boston University. The goal of our
      study was to demonstrate that such an interactive, team-based approach to
      teaching anatomy would be well received and be helpful in recall, comprehension,
      and reinforcement of anatomy learned in the first year of medical school.
      MATERIALS AND METHODS: Each radiology-anatomy correlation lab was focused on one
      particular anatomic part, such as skull base, pelvis, coronary anatomy, etc. Four
      stations, including a three-dimensional model, computer, ultrasound, and posters,
      were created for each lab. Informed consent was obtained before online survey
      dissemination to assess the effectiveness and quality of radiology-anatomy
      correlation lab. This study was approved by our institutional institutional
      review board, and data were analyzed using a chi(2) test. RESULTS: Survey data
      were collected from February 2010 through March 2012. The response rate was
      33.5%. Overall, the highest percentage of students (46%) found the three
      dimensional model station to be the most valuable. The computer station was most
      helpful in recall of the anatomic principles from the first year of medical
      school. Regarding the quality of the anatomy lab, less than 2% of the students
      thought that the images were of poor quality or the material presented was not
      clinically relevant. DISCUSSION: Our results indicate that an interactive, team
      based approach to teaching anatomy was well received by the medical students. It
      was engaging and students were able to benefit from it in multiple ways.

PMID- 24029066
TI  - Inherent limitations of multiple-choice testing.

PMID- 24029067
TI  - Radiology grows ahead in a second century.

PMID- 24029068
TI  - Peptides presented by HLA class I molecules in the human thymus.
AB  - The thymus is the organ in which T lymphocytes mature. Thymocytes undergo
      exhaustive selection processes that require interactions between the TCRs and
      peptide-HLA complexes on thymus antigen-presenting cells. The thymic peptide
      repertoire associated with HLA molecules must mirror the peptidome that mature T
      cells will encounter at the periphery, including peptides that arise from tissue
      restricted antigens. The transcriptome of specific thymus cell populations has
      been widely studied, but there are no data on the HLA-I peptidome of the human
      thymus. Here, we describe the HLA-I-bound peptide repertoire from thymus samples,
      showing that it is mostly composed of high-affinity ligands from cytosolic and
      nuclear proteins. Several proteins generated more than one peptide, and some
      redundant peptides were found in different samples, suggesting the existence of
      antigen immunodominance during the processes that lead to central tolerance.
      Three HLA-I ligands were found to be derived from proteins expressed by stromal
      cells, including one from the protein TBATA (or SPATIAL), which is present in the
      thymus, brain and testis. The expression of TBATA in medullary thymic epithelial
      cells has been reported to be AIRE dependent. Thus, this report describes the
      first identification of a thymus HLA-I natural ligand derived from an AIRE
      dependent protein with restricted tissue expression. BIOLOGICAL SIGNIFICANCE: We
      present the first description of the HLA-I-bound peptide repertoire from ex vivo
      thymus samples. This repertoire is composed of standard ligands from cytosolic
      and nuclear proteins. Some peptides seem to be dominantly presented to thymocytes
      in the thymus. Most importantly, some HLA-I associated ligands derived from
      proteins expressed by stromal cells, including one peptide, restricted by HLA
      A*31:01, arising from an AIRE-dependent protein with restricted tissue
      expression.

PMID- 24029070
TI  - Zinc regulation of transcriptional activity during retinoic acid-induced neuronal
      differentiation.
AB  - Zinc deficiency impairs the proliferation and differentiation of stem cells in
      the central nervous system that participate in neurogenesis. To examine the
      molecular mechanisms responsible for the role of this essential nutrient in
      neuronal precursor cells and neuronal differentiation, we identified zinc
      dependent changes in the DNA-binding activity of zinc finger proteins and other
      transcription factors in proliferating human Ntera-2 neuronal precursor cells
      undergoing retinoic acid-stimulated differentiation into a neuronal phenotype. We
      found that zinc deficiency altered binding activity of 28 transcription factors
      including retinoid X receptor (RXR) known to participate in neuronal
      differentiation. Alterations in zinc finger transcription factor activity were
      not simply the result of removal of zinc from these proteins during zinc
      deficiency, as the activity of other zinc-binding transcription factors such as
      the glucocorticoid receptor was increased by as much as twofold over zinc
      adequate conditions, and nonzinc-binding transcription factors such as nuclear
      factor-1 and heat shock transcription factor-1 were increased by as much as
      fourfold over control. Western analysis did not detect significant decreases in
      total RXR protein abundance in neuronal precursors, suggesting that the decrease
      in DNA-binding activity was not simply the result of a reduction in RXR levels in
      neuronal precursor cells. Rather, use of a reporter gene construct containing
      retinoic acid response elements upstream from a luciferase coding sequence
      revealed that zinc deficiency results in decreased transcriptional activity of
      RXR and reductions in retinoic acid-mediated gene transcription during neuronal
      differentiation. These results show that zinc deficiency has implications for
      both developmental and adult neurogenesis. 

PMID- 24029071
TI  - Bacteriophage T5 encodes a homolog of the eukaryotic transcription coactivator
      PC4 implicated in recombination-dependent DNA replication.
AB  - The RNA polymerase II cofactor PC4 globally regulates transcription of protein
      encoding genes through interactions with unwinding DNA, the basal transcription
      machinery and transcription activators. Here, we report the surprising
      identification of PC4 homologs in all sequenced representatives of the T5 family
      of bacteriophages, as well as in an archaeon and seven phyla of eubacteria. We
      have solved the crystal structure of the full-length T5 protein at 1.9A,
      revealing a striking resemblance to the characteristic single-stranded DNA
      (ssDNA)-binding core domain of PC4. Intriguing novel structural features include
      a potential regulatory region at the N-terminus and a C-terminal extension of the
      homodimerisation interface. The genome organisation of T5-related bacteriophages
      points at involvement of the PC4 homolog in recombination-dependent DNA
      replication, strongly suggesting that the protein corresponds to the hitherto
      elusive replicative ssDNA-binding protein of the T5 family. Our findings imply
      that PC4-like factors intervene in multiple unwinding-related processes by acting
      as versatile modifiers of nucleic acid conformation and raise the possibility
      that the eukaryotic transcription coactivator derives from ancestral DNA
      replication, recombination and repair factors. 

PMID- 24029072
TI  - Risk factors for sporadic domestically acquired Salmonella serovar Enteritidis
      infections: a case-control study in Ontario, Canada, 2011.
AB  - In Ontario, Canada, the number of Salmonella Enteritidis (SE) cases increased
      over the years 2005-2010. A population-based case-control study was undertaken
      from January to August 2011 for the purpose of identifying risk factors for
      acquiring illness due to SE within Ontario. A total of 199 cases and 241 controls
      were enrolled. After adjustment for confounders, consuming any poultry meat
      [adjusted odds ratio (aOR) 2.24, 95% confidence interval (CI) 1.31-3.83],
      processed chicken (aOR 3.32, 95% CI 1.26-8.76) and not washing hands following
      handling of raw eggs (OR 2.82, 95% CI 1.48-5.37) were significantly associated
      with SE infection. The population attributable fraction was 46% for any poultry
      meat consumption and 10% for processed chicken. Poultry meat continues to be
      identified as a risk factor for SE illness. Control of SE at source, as well as
      proper food handling practices, are required to reduce the number of SE cases.

PMID- 24029069
TI  - Recent advances in understanding the anti-diabetic actions of dietary flavonoids.
AB  - Flavonoids are polyphenolic compounds that are abundant in fruits and vegetables,
      and increasing evidence demonstrates a positive relationship between consumption
      of flavonoid-rich foods and disease prevention. Epidemiological, in vitro and
      animal studies support the beneficial effects of dietary flavonoids on glucose
      and lipid homeostasis. It is encouraging that the beneficial effects of some
      flavonoids are at physiological concentrations and comparable to clinically-used
      anti-diabetic drugs; however, clinical research in this field and studies on the
      anti-diabetic effects of flavonoid metabolites are limited. Flavonoids act on
      various molecular targets and regulate different signaling pathways in pancreatic
      beta-cells, hepatocytes, adipocytes and skeletal myofibers. Flavonoids may exert
      beneficial effects in diabetes by (i) enhancing insulin secretion and reducing
      apoptosis and promoting proliferation of pancreatic beta-cells; (ii) improving
      hyperglycemia through regulation of glucose metabolism in hepatocytes; (iii)
      reducing insulin resistance, inflammation and oxidative stress in muscle and fat
      and (iv) increasing glucose uptake in skeletal muscle and white adipose tissue.
      This review highlights recent findings on the anti-diabetic effects of dietary
      flavonoids, including flavan-3-ols, flavanones, flavonols, anthocyanidins,
      flavones and isoflavones, with particular emphasis on the studies that
      investigated the cellular and molecular mechanisms involved in the beneficial
      effects of the compounds. 

PMID- 24029074
TI  - On the value of probability for evaluating results of comparative pattern
      analyses.
AB  - This letter to the Editor comments on the article Practical relevance of pattern
      uniqueness in forensic science by P.T. Jayaprakash (Forensic Science
      International, in press). 

PMID- 24029073
TI  - Understanding the role of NRF2-regulated miRNAs in human malignancies.
AB  - Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a key transcription factor
      that regulates the expression of over a hundred cytoprotective and antioxidant
      genes that provide cellular protection from reactive oxygen species. Chemotherapy
      resistance in several cancers has been linked to dysregulation of the NRF2
      signalling pathway, moreover there is growing evidence that NRF2 may contribute
      to tumorigenesis. MicroRNA (miRNA) are small non-coding RNA sequences that post
      transcriptionally regulate mRNA sequences. In cancer pathogenesis, aberrantly
      expressed miRNAs can act as either tumor suppressor or oncogenic miRNA. Recent
      evidence has been described that identifies a number of miRNA that can be
      regulated by NRF2. This review outlines the importance of NRF2 in regulating
      miRNA, and the functional role this may have in the tumorigenesis of human
      malignancies and their chemotherapy resistance. 

PMID- 24029075
TI  - Effect of drought and combined drought and heat stress on polyamine metabolism in
      proline-over-producing tobacco plants.
AB  - The roles of proline and polyamines (PAs) in the drought stress responses of
      tobacco plants were investigated by comparing the responses to drought alone and
      drought in combination with heat in the upper and lower leaves and roots of wild
      type tobacco plants and transformants that constitutively over-express a modified
      gene for the proline biosynthetic enzyme Delta1-pyrroline-5-carboxylate
      synthetase (P5CSF129A; EC 2.7.2.11/1.2.1.41). In both genotypes, drought stress
      coincided with a decrease in relative water content (RWC) that was much less
      severe in the upper leaves than elsewhere in the plant. The drought also
      increased proline levels in both genotypes. A brief period of heat stress (2 h at
      40  degrees C) at the end of the drought period did not significantly influence
      the proline levels in the upper leaves and roots but caused a further increase in
      the lower leaves of both genotypes. The rate at which these elevated proline
      levels returned to normal during the post-stress recovery period was slower in
      the transformants and plants that had been subjected to the combined stress. In
      both genotypes, drought stress significantly reduced the levels of spermidine
      (Spd) and putrescine (Put) in the leaves and roots relative to those for
      controls, and increased the levels of spermine (Spm) and diaminopropane (Dap,
      formed by the oxidative deamination of Spd and Spm). Spd levels may have declined
      due to its consumption in Spm biosynthesis and/or oxidation by polyamine oxidase
      (PAO; EC 1.5.3.11) to form Dap, which became more abundant during drought stress.
      During the rewatering period, the plants' Put and Spd levels recovered quickly
      and the activity of the PA biosynthesis enzymes in their leaves and roots
      increased substantially; this increase was more pronounced in transformants than
      WT plants. The high levels of Spm observed in drought stressed plants persisted
      even after the 24 h recovery and rewatering phase. The malondialdehyde (MDA)
      contents of the lower leaves of WTs increased substantially during the drought
      stress period; a less pronounced increase occurred in the transformants and after
      the application of the combined stress. After the post-stress recovery period,
      the MDA contents in the leaves of both genotypes were higher than those in the
      corresponding controls. The MDA contents of the upper leaves in plants of both
      genotypes remained relatively constant throughout, indicating that these leaves
      are preferentially protected against the adverse effects of oxidative stress and
      demonstrating the efficiency of the plants' induced antioxidative defense
      mechanisms. 

PMID- 24029076
TI  - A critical functional missense mutation (H173R) in the bovine PROP1 gene
      significantly affects growth traits in cattle.
AB  - The PROP1 protein, encoded by the prophet of Pit-1 (PROP1) gene, exhibits both
      DNA-binding and transcriptional activation abilities. Its expression leads to the
      ontogenesis of growth hormone (GH), prolactin (PRL), thyroid-stimulating hormone
      (TSH), and pituitary hormone. The missense mutation H173R in PROP1 may result in
      deficiencies of GH, PRL, TSH, and Pit-1, thereby affecting growth traits. The
      objective of this study was to characterize the H173R mutation within the PROP1
      gene and examine its associations with growth traits in cattle. Accordingly, the
      H173R mutation was genotyped in 1207 cows belonging to five Chinese native
      breeds. Three genotypes were identified among the specimens, with genotype AA
      being the major one. Consequently, the "G" allele was the minor allele.
      Association testing revealed that the H173R mutation was significantly associated
      with body weight, average daily weight gain and physical parameters in the
      analyzed breeds. Interestingly, the cows with genotype AG and/or AA had superior
      growth traits compared with those expressing the GG genotype, in all tested
      breeds. These findings revealed that the "A" allele had positive effects on
      growth traits, which was consistent with the increasing binding ability and
      enhanced activation capacity associated with the bovine isoform PROP1-173H,
      representing the "A" allele. Therefore, the H173R mutation can be considered as a
      DNA marker for selecting individuals with superior growth traits, thereby
      contributing to research on breeding and genetics in the beef industry. 

PMID- 24029077
TI  - Mowat-Wilson syndrome detected by using high resolution microarray.
AB  - Individuals with Mowat-Wilson syndrome (MWS; OMIM#235730) have characteristic
      facial features, a variety of congenital anomalies such as Hirschsprung disease,
      and intellectual disabilities caused by mutation or deletion of ZEB2 gene. This
      deletion or cytogenetic abnormality has been reported primarily from Europe,
      Australia and the United States, but not in Korea. Here we report a patient with
      characteristic facial features of MWS, developmental delay and spasticity. High
      resolution microarray analysis revealed 0.9 Mb deletion of 2q22.3 involving two
      genes: ZEB2 and GTDC1. This case shows the important role of high resolution
      microarray in patients with unexplained psychomotor retardation and/or facial
      dysmorphism. Knowledge about the most striking clinical signs and implementation
      of effective molecular tests like microarray could significantly increase the
      detection rate of new cases of MWS in Korea. This is the first reported case of
      MWS in Korea.

PMID- 24029078
TI  - A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial
      seizures in infancy.
AB  - We performed analysis of KCNT1 in two unrelated patients with malignant migrating
      partial seizures in infancy. Both patients had intractable focal seizures since
      two months of age. Their seizures were characterized by a shift of epileptic
      focus during a single seizure and were resistant to most antiepileptic drugs but
      responded to vagus nerve stimulation in one and clorazepate in the other.
      Bidirectional sequencing for KCNT1 was analyzed by standard Sanger sequencing
      method. A de novo c.862G>A (p.Gly288Ser) missense mutation was identified at the
      pore region of KCNT1 channel in both patients, whereas all KCNT1 mutations in the
      previous reports were identified mostly in the intracellular C-terminal region.
      Computational analysis suggested possible changes in the molecular structure and
      the ion channel property induced by the Gly288Ser mutation. Because the G-to-A
      transition was located at CG dinucleotide sequences as previously reported for
      KCNT1 mutations, the recurrent occurrence of de novo KCNT1 mutations indicated
      the hot spots of these locations. 

PMID- 24029079
TI  - Cloning of the Lentinula edodes B mating-type locus and identification of the
      genetic structure controlling B mating.
AB  - During the life cycle of heterothallic tetrapolar Agaricomycetes such as
      Lentinula edodes (Berk.) Pegler, the mating type system, composed of unlinked A
      and B loci, plays a vital role in controlling sexual development and resulting
      formation of the fruit body. L. edodes is produced worldwide for consumption and
      medicinal purposes, and understanding its sexual development is therefore of
      great importance. A considerable amount of mating type factors has been indicated
      over the past decades but few genes have actually been identified, and no
      complete genetic structures of L. edodes B mating-type loci are available. In
      this study, we cloned the matB regions from two mating compatible L. edodes
      strains, 939P26 and 939P42. Four pheromone receptors were identified on each new
      matB region, together with three and four pheromone precursor genes in the
      respective strains. Gene polymorphism, phylogenetic analysis and distribution of
      pheromone receptors and pheromone precursors clearly indicate a bipartite matB
      locus, each sublocus containing a pheromone receptor and one or two pheromone
      precursors. Detailed sequence comparisons of genetic structures between the matB
      regions of strains 939P42, 939P26 and a previously reported strain SUP2 further
      supported this model and allowed identification of the B mating type subloci
      borders. Mating studies confirmed the control of B mating by the identified
      pheromone receptors and pheromones in L. edodes.

PMID- 24029081
TI  - Optical absorption and emission of alpha-Sn nanocrystals from first principles.
AB  - We investigate the optical properties of hydrogenated alpha-Sn nanocrystals up to
      diameters of 3.6 nm in the framework of an ab initio pseudopotential method
      including spin-orbit interaction (SOI) and the repeated supercell approximation.
      The fundamental absorption and emission edges are determined including
      quasiparticle effects and electron-hole interaction. The atomic geometries in the
      ground and excited electronic states follow from total energy optimization. We
      discuss the oscillator strengths of the optical absorption near the fundamental
      gaps for the most important transitions. We demonstrate that the spectra can only
      be correctly described including SOI. The strongly size-dependent Stokes shifts
      between optical absorption and emission are shown to be mainly a consequence of
      the different atomic geometries.

PMID- 24029080
TI  - Functional analysis and tissue-differential expression of four FAD2 genes in
      amphidiploid Brassica napus derived from Brassica rapa and Brassica oleracea.
AB  - Fatty acid desaturase 2 (FAD2), which resides in the endoplasmic reticulum (ER),
      plays a crucial role in producing linoleic acid (18:2) through catalyzing the
      desaturation of oleic acid (18:1) by double bond formation at the delta 12
      position. FAD2 catalyzes the first step needed for the production of
      polyunsaturated fatty acids found in the glycerolipids of cell membranes and the
      triacylglycerols in seeds. In this study, four FAD2 genes from amphidiploid
      Brassica napus genome were isolated by PCR amplification, with their enzymatic
      functions predicted by sequence analysis of the cDNAs. Fatty acid analysis of
      budding yeast transformed with each of the FAD2 genes showed that whereas BnFAD2
      1, BnFAD2-2, and BnFAD2-4 are functional enzymes, and BnFAD2-3 is nonfunctional.
      The four FAD2 genes of B. napus originated from synthetic hybridization of its
      diploid progenitors Brassica rapa and Brassica oleracea, each of which has two
      FAD2 genes identical to those of B. napus. The BnFAD2-3 gene of B. napus, a
      nonfunctional pseudogene mutated by multiple nucleotide deletions and insertions,
      was inherited from B. rapa. All BnFAD2 isozymes except BnFAD2-3 localized to the
      ER. Nonfunctional BnFAD2-3 localized to the nucleus and chloroplasts. Four BnFAD2
      genes can be classified on the basis of their expression patterns. 

PMID- 24029082
TI  - Infant mortality: a call to action overcoming health disparities in the United
      States.
AB  - Among all of the industrialized countries, the United States has the highest
      infant mortality rate. Racial and ethnic disparities continue to plague the
      United States with a disproportionally high rate of infant death. Furthermore,
      racial disparities among infant and neonatal mortality rates remain a chronic
      health problem in the United States. These risks are based on the geographical
      variations in mortality and disparities among differences in maternal risk
      characteristics, low birth weights, and lack of access to health care. 

PMID- 24029083
TI  - Susceptibility-weighted imaging, an additional tool to diagnose brain death:
      initial experience.
AB  - We describe findings suggestive of brain death on susceptibility-weighted
      imaging. We retrospectively reviewed brain magnetic resonance (MR) images of 15
      patients who had cardiac arrest and found four cases with evidence of brain
      death. We then reviewed susceptibility-weighted imaging (SWI) findings on these
      cases. SWI images in the four cases with brain death showed deoxygenated blood in
      intracranial arteries. This preliminary result suggests that SWI may be used to
      diagnose brain death. 

PMID- 24029084
TI  - Vertebral and Basilar Arteries: Transcranial Color-Coded Duplex Ultrasonography
      versus Conventional TCD in Detection of Narrowings.
AB  - We prospectively compared the accuracies of conventional transcranial Doppler
      ultrasound (TCD) and transcranial color-coded duplex sonography (TCCS) in the
      diagnosis of narrowing of the basilar (BA) and vertebral arteries (VA). Fifty-six
      consecutive patients (mean age 55.8 years; 34 women) after subarachnoid
      hemorrhage (n=46), stroke or transient ischemic attack (n=5), and for other
      reasons (n=5) underwent on the same day TCD, TCCS and the intra-arterial digital
      subtraction angiography (DSA) - the reference standard. The accuracy of peak
      systolic (VPS), mean (VM), and end-diastolic velocities (VED) in detection of any
      arterial narrowing was estimated using the receiver operator characteristic (ROC)
      curve methodology and the total area (Az) under the curve. Accuracy of TCCS in
      detection of VA narrowing based on VPS and VM measurements was significantly
      higher than accuracy of TCD (Az=0.65 for VPS and Az=0.62 for VM versus Az=0.51
      and Az=0.50, respectively, p<0.05 for both). Accuracy of TCCS in detection of BA
      narrowing was also higher than accuracy of TCD based on VPS measurements (Az=0.69
      versus Az=0.50, respectively), with a trend toward significant difference,
      p=0.085. The accuracy of TCCS is superior to accuracy of TCD in detection of
      narrowings of vertebral and basilar arteries, thus TCCS should be preferred in
      routine clinical practice. 

PMID- 24029085
TI  - Imaging characteristics of cavernous sinus cavernous hemangiomas.
AB  - Cavernous hemangiomas occur rarely in the cavernous sinus and are difficult to
      diagnose preoperatively. The imaging of these lesions resembles other benign
      paracavernous lesions such as schwannomas and meningiomas. Profuse intraoperative
      bleeding may be encountered during surgical resection of these lesions. A
      preoperative diagnosis is therefore important to alert the surgeon. We report on
      the imaging characteristics of two different histopathological types of cavernous
      sinus cavernous hemangiomas and the use of contrast-enhanced MRI, diffusion
      weighted MRI and magnetic resonance spectroscopy in the differential diagnosis of
      these lesions. 

PMID- 24029086
TI  - Cerebral amyloid angiopathy.
AB  - The aim of this report was to describe the case of an elderly patient with
      cerebral amyloid angiopathy and associated dementia who presented with new onset
      symptomatology compatible with an acute cerebrovascular event. Computed
      tomography scanning was suggestive of an incipient ischemic cerebrovascular
      event. Magnetic resonance imaging was requested due to the presence of small
      hyperdense lesions on CT, and revealed multiple diffuse hypodense parenchymal
      lesions with hemosiderin deposits, indicative of cerebral amyloid angiopathy.
      Diagnosis of the underlying pathology is of importance, as aspirin use, and
      antiplatelet use in general, may in these patients be associated with microbleed
      burden. 

PMID- 24029087
TI  - An Atypical Case of Chiari II Malformation Mimicking Partial
      Rhombencephalosynapsis.
AB  - Partial rhombencephalosynapsis in the presence of Chiari II malformation has been
      proposed as a "new abnormality of the hindbrain and spine". We describe a case of
      Chiari II malformation with imaging features mimicking partial
      rhombencephalosynapsis. Our case demonstrates how the imaging findings of Chiari
      II malformation can be confused with the above entity and highlights the
      differentiating features to help radiologists make an accurate diagnosis. 

PMID- 24029088
TI  - Endovascular treatment of A1 aneurysms. A series of five cases with a brief
      literature review.
AB  - Aneurysms of the A1 segment of the anterior cerebral artery are rare and
      represent less than 1% of intracranial aneurysms. There are few reports available
      in the literature describing the role of endovascular management of these rare
      aneurysms. In the present series we describe five patients with A1 aneurysms
      presenting at our institution with various clinical presentations, treated
      successfully by endovascular method with a good clinical outcome. From January
      2008 to July 2011, five patients (two males and three females) with A1 aneurysms
      were treated by endovascular means. Four of the patients presented with
      subarachnoid hemorrhage due to rupture of the A1 aneurysm and one patient
      presented with symptoms of mass effect in the form of headache and
      ophthalmoplegia. The age group ranges from eight to 52 years with a mean age of
      34.2 years. Four of the patients were treated by coiling without any assisted
      technique whereas one patient who had a dissecting fusiform aneurysm was treated
      with stent-assisted coiling. Technical success was achieved in all the
      patients.We did not encounter any procedure-related complications in any of our
      cases. All the patients had an uneventful course with good clinical outcome.
      Angiographic follow-up was available in four patients (80%). Endovascular
      treatment of this rare group of aneurysms is an effective and safe treatment
      modality, however large series are required to support our findings. 

PMID- 24029089
TI  - Complications caused by cerebral arteriovenous malformation embolization.
AB  - We describe the complications of endovascular embolization for cerebral
      arteriovenous malformations (AVMs). 164 consecutive patients with AVMs treated by
      endovascular embolization between 1998 and 2003 were retrospectively reviewed.
      Over a five-year period, 292 embolization procedures were performed in 164
      patients with embolization as the primary treatment modality (n=126) or as an
      adjunct to surgery (n =14) or radiosurgery (n=24). There were a total of 15 (9.1%
      per patient, 5.1% per procedure) complications in this series, of which 14 were
      clinically significant (8.5% of patients, 4.8% per procedure), and one was a
      technical complication (0.6% of patients, 0.3% per procedure). Excellent or good
      outcomes (Glasgow Outcome Scale >= 4) were observed in 136 (82.9%) patients at
      discharge. Neurological deficits (Glasgow Outcome Scale 1-4) as a direct result
      of embolization were 7.3% at discharge. In a single-center, retrospective,
      nonrandomized study, 82.9% of patients had excellent or good outcomes at
      discharge after AVM embolization, with a complication rate of 5.1%. 

PMID- 24029090
TI  - A single center experience of stenting in symptomatic intracranial
      atherosclerosis.
AB  - Atherosclerotic intracranial arterial stenosis is an important cause of stroke
      that is increasingly being treated with percutaneous transluminal angioplasty and
      stenting (PTAS) to prevent recurrent stroke. However, PTAS has been compared with
      medical management in a randomized trial (SAMMPRIS), where aggressive medical
      management was superior to PTAS with the use of the Wingspan stent system,
      however in our experience we have had good results and have experienced no
      complications with this therapy. In a retrospective, single-center study we
      enrolled seven consecutive patients with a symptomatic angiographically proven
      atherosclerotic intracranial arterial stenosis of the anterior and posterior
      circulation. All cases received adjuvant therapy (aspirin and clopidogrel or
      ticlopidine) before and after deployment of the device. The procedures were
      performed with the patient under general anesthesia. We use the Wingspan stent
      system. The occlusion site was middle cerebral artery (MCA) in three patients,
      proximal internal carotid artery (ICA) in one patient and vertebrobasilar artery
      in three patients. Primary interventional successful revascularization was
      achieved in all cases. Four patients had no residual stenosis, and the other
      three had 20%, 30% and 40% residual stenosis (Table 1). All patients showed a
      clinical improvement after stent deployment. No peri-interventional events or
      neurologic complications occurred directly related to the technique. Patency rate
      was 100% at the last examination in six cases, one case had a pre-occlusive
      stenosis, requiring angioplasty. No patients died during the follow-up period,
      and 100% of patients showed good functional outcome at three months (modified
      Rankin Scale score <= 2). Although the SAMMPRIS study showed that aggressive
      medical management was superior to PTAS, our results suggest that intracranial
      stenting is safe and effective, probably due to an extraordinary selection of
      candidates and to an exquisite technique. 

PMID- 24029091
TI  - Traumatic dissecting posterior cerebral artery aneurysm. A case report and review
      of the literature.
AB  - Dissecting posterior cerebral artery (PCA) aneurysms are among rare
      cerebrovascular malformations accounting for 2% to 6% of all aneurysms. Herein we
      describe a case of pediatric dissecting aneurysm located in the PCA with
      documentation of aneurysm development. In addition, we discuss its treatment with
      a new therapeutic method involving glue injection. 

PMID- 24029092
TI  - A rare case of intracranial rosai-dorfman disease mimicking multiple meningiomas.
      A case report and review of the literature.
AB  - Rosai-Dorfman disease (RDD) was firstly described in 1969 as a benign
      proliferative disorder of histiocytes with systemic symptoms and lymphadenopathy.
      This disease is of uncertain pathogenesis and mostly occurs in children and young
      adults. The typical clinical features of RDD include bilateral painless cervical
      lymphadenopathy, but extranodal involvement may also be present. The most common
      extranodal sites include organs such as the respiratory tract, skin, nasal
      cavity, orbit and bone. Isolated central nervous system (CNS) manifestations are
      extremely rare. In case of CNS involvement, the commonest imaging findings are
      dural-based extra-axial enhancing masses. We describe a case of intracranial RDD
      mimicking multiple meningiomas both clinically and radiologically in a 57-year
      old man presenting with a six-year history of progressive right visual and
      hearing loss and tinnitus. In cases of multiple extra-axial lesions it is worth
      bearing in mind the possible differential diagnosis for intracranial RDD and
      eventually propose to the patient further investigations. 

PMID- 24029093
TI  - Magnetic Resonance Spectroscopy for Differentiating Pseudo-Progression from True
      Progression in GBM on Concurrent Chemoradiotherapy.
AB  - Neoadjuvant chemo-radiation therapy including temozolomide is commonly used for
      the treatment of gliomas. However, increased lesion size and contrast enhancement
      are frequently observed following this therapy and this appearance is termed as
      'pseudo-progression'. Since conventional imaging is unable to differentiate
      pseudo-progression from tumour recurrence, we evaluated the utility of MR
      spectroscopy (MRS) to differentiate these two pathological entities. Longitudinal
      MRI and MRS studies prior to and within four months post chemo-radiation therapy
      including diffusion-weighted imaging and single voxel spectroscopy (short and
      intermediate echo) were performed in 62 glioblastoma (GBM) patients undergoing
      chemo-radiation therapy. Clinical follow-up demonstrated four cases of pseudo
      progression. In this study, results from these four cases and a known case of
      tumour recurrence are reported. Metabolite ratios and presence or absence of
      lipids at 1.3 ppm were used to differentiate between pseudo-progression and
      tumour recurrence. All four cases of pseudo-progression demonstrated elevated
      lipid signals on MRS. Additionally, an absence of choline or a low choline/NAA
      ratio was also observed. In comparison, the patient with tumour recurrence showed
      lower lipid signals and a high choline/NAA ratio. The presence of elevated lipid
      signals along with low choline/NAA ratios can aid in differentiation of pseudo
      progression from tumour recurrence. 

PMID- 24029094
TI  - Leiomyosarcoma leptomeningeal brain metastases.
AB  - Brain metastases from soft tissue sarcomas (STS) occur late and relatively
      rarely, most commonly after lung metastases have developed. Furthermore, they are
      most commonly intraparenchymal in distribution. We describe two cases of
      histologically confirmed intracranial metastatic soft tissue leiomyosarcomas. In
      both cases all the nodular metastases measuring 10 mm in diameter or less could
      be easily detected in the leptomeningeal spaces by MRI. However, as the lesion
      enlarges it is difficult to recognize the site of origin, and the mass appears
      and behaves as intra-axial. Lesions located in the leptomeningeal spaces and in
      the perivascular space can be extremely small, which makes their detection
      problematic. For this reason we believe that in this context, MRI global
      gadolinium enhanced imaging using contiguous 1 mm slice thickness acquisition (TR
      23 ms,TE 8 ms 512*512 matrix) is preferable, since the patient's management may
      vary depending on the multiplicity and location of the lesions. 

PMID- 24029095
TI  - Spontaneous regression of syringomyelia in a young patient with Chiari type I
      malformation.
AB  - Syringomyelia is a disorder in which a cyst or cavity forms within the spinal
      cord. This cyst, called syrinx, can expand and elongate over time, destroying the
      spinal cord. We describe the case of a young patient with partial spontaneous
      regression of syringomyelia in Chiari I malformation, confirmed by magnetic
      resonance imaging three years after the diagnosis. During this period the patient
      did not experience any clinical symptoms. Although described in literature,
      spontaneous regression is an unusual event and very few cases have been reported.
      This case report supports the belief that conservative management together with
      both clinical and imaging periodic controls should be preferred in stable mild
      symptomatic patients. 

PMID- 24029096
TI  - Imaging of cervical extradural en-plaque meningioma. A case report.
AB  - Meningioma is one of the most common spinal extramedullary tumors, largely
      intradural. An extradural localization is possible but less frequent. There are
      two morphologically different types of meningioma: one is round, and the other is
      the "en-plaque" form, that grows along the dura mater like a sheet. The "en
      plaque" form, is unusual. We report on an unusual case of epidural and
      extraspinal "en-plaque" meningioma, describing the MRI and CT features and
      discussing the possible principal differential diagnosis (neurolymphomatosis,
      plexiform neurofibromas/schwannomas and metastasis). 

PMID- 24029097
TI  - Imaging characteristics of primary spinal primitive neuroectodermal tumors. A
      report of five cases and literature review.
AB  - Primary spinal primitive neuroectodermal tumors (PNETs) are rare and classified
      into peripheral and central types because the treatment strategy and outcome are
      different. This study describes five cases of primary spinal peripheral type
      PNETs. Magnetic resonance imaging showed large extradural masses in the cervical
      and thoracic spine with bony invasion and paraspinal extension in four cases and
      a transdural mass in the sacral spinal canal in one case. We also briefly
      summarize the imaging characteristics of 36 peripheral type and six central type
      primary spinal PNETs in the literature. 

PMID- 24029098
TI  - MRI features of spinal solitary fibrous tumors. A report of two cases and
      literature review.
AB  - Spinal solitary fibrous tumors (SFT) are very rare neoplasms occurring in the
      spinal canal, with only 38 cases reported in ten years since the first
      description. We describe two cases of SFT of the spine and review 33 well
      documented cases in the literature to define distinctive radiological and
      surgical features raising the suspicion of a spinal SFT before histological
      verification. A 67-year-old man with cervical myeloradiculopathy had a large
      extramedullary tumor of the cervical spinal canal extending from C4 to C7. On MRI
      the tumor was isointense on T1-sequences and hypointense on T2-sequences, and had
      marked contrast enhancement. At surgery, the tumor was intradural extramedullary,
      with no dural or root attachment, but it was adherent to the cord. Complete tumor
      removal was achieved with good outcome. A 75-year-old man with progressive
      thoracic myelopathy had an intramedullary tumor at C6 and C7 level, which was
      hypointense on T1- and T2-weighted images of MRI. At surgery, the tumor was
      intramedullary and strongly adherent to the cord; it was successfully removed.
      Both tumors were composed of elongated cells with a collagen-matrix background.
      Immunohistochemical staining was positive for vimentin, CD34, and bcl-2, and
      negative for EMA and S-100 protein. A careful analysis of our own and the other
      reported cases of spinal SFTs may disclose some peculiar features of this rare
      tumor. A spinal intramedullary or extramedullary tumor, hypointense on T2
      weighted images of MRI, which intraoperatively shows hard consistency, scarce
      vascularization, no nerve root involvement, no or weak dural attachment, absence
      of arachnoidal interface, and adherence to the spinal cord may suggest the
      diagnosis of SFT. 

PMID- 24029099
TI  - Spontaneous migration of a redundant nerve root accompanied by absorption of
      lumbar disk herniation. A case report.
AB  - A redundant nerve root is defined as a large, elongated and tortuous nerve root
      commonly associated with severe lumbar spinal canal stenosis. Elongation of nerve
      roots as a result of mechanical trapping at stenotic level is assumed to be a
      possible mechanism. Here we present a case in a patient who showed a redundant
      nerve root above the level of a lumbar canal stenosis caused by disk herniation
      and redundancy spontaneously migrating to a lower lumbar stenosis level
      accompanied by absorption of the herniated disk as shown by magnetic resonance
      imaging (MRI). A 67-year-old Japanese woman presented with bilateral thigh/leg
      pain and intermittent claudication. A midsagittal T2-weighted MR image of the
      lumbar spine revealed severe spinal canal stenosis at the L3-4 and L4-5 levels.
      At the L3-4 level, central disk herniation compressed the dural tube. An MR image
      revealed redundant nerve roots just cranial to the severely compressed L3-4
      level. A follow-up MRI study revealed regression of disk herniation at the L3-4
      level. In contrast, there was no significant change of the stenosis at the L4-5
      level. Sagittal T2-weighted MR imaging at follow-up revealed redundant nerve
      roots just cranial to the L4-5 level, whereas the redundant nerve roots cranial
      to the L3-4 level had disappeared. The MRI findings of the present case support
      the "squeeze" hypothesis as causative of redundant nerve roots. 

PMID- 24029100
TI  - Spinal gout: a great mimicker. A case report and literature review.
AB  - Spinal gout is not as rare as was previously thought and mimics heterogeneous
      spinal conditions such as rheumatoid, septic, seronegative arthropathies and
      primary or secondary neoplasms. Imaging findings are nonspecific and usually
      manifest late. In clinical settings, suspicious for spinal gout, needle biopsy
      may help for further characterization. A 57-year-old man with no significant past
      medical history presented in the emergency department with severe non radiating
      low back pain of one week duration. His laboratory tests were significant for
      uric acid of 642 MUmol/L, erythrocyte sedimentation rate 93 mm/hour, and C
      reactive protein 8.3 mg/dl. The lumbar spine MRI showed nonspecific acute
      inflammatory extensive lumbar facet arthropathy and soft tissue enhancement. The
      radiological and clinical information was insufficient to differentiate among
      septic arthritis, rheumatoid arthritis, seronegative arthropathy or gout. A
      lumbar facet fluoroscopy-fluoroscopic CT-guided needle biopsy was performed. The
      biopsy demonstrated negative birefringent crystals consistent with gout. Although
      the spinal gout is not rare, few case reports describe the role of needle biopsy
      and mimics. We present a comparative review of limited reports addressing the
      role of needle biopsy in mimics of spinal gout. 

PMID- 24029101
TI  - Shrinkage stress development in dental composites--an analytical treatment.
AB  - OBJECTIVES: The aim of this paper is to develop a comprehensive mathematical
      model for shrinkage stress development in dental composites that can account for
      the combined effect of material properties, specimen geometry and external
      constraints. METHODS: A viscoelastic model that includes the composite's elastic,
      creep and shrinkage strains, and their interaction with the sample's dimensions
      and the external constraint is developed. The model contains two dimensionless
      parameters. The first one represents the compliance of the external constraint
      relative to that of the composite sample, and the second controls the rate of
      shrinkage stress decay through creep. The resulting differential equation is
      solved for two special cases: zero compliance and zero creep. Predictions for
      shrinkage stress measurements are then made using the analytical solutions for
      instruments with different compliances, samples with different thicknesses and
      composites with different filler fractions. RESULTS: The model correctly predicts
      how shrinkage stress increases with time, its dependence on the interaction
      between the entire system's compliance and the material properties, and the
      effect of the filler fraction on its maximum value. Comparisons with reported
      shrinkage stress measurements have provided very good agreement between theory
      and experiments. SIGNIFICANCE: The results provided by the model can help to
      resolve most, if not all, of the seemingly conflicting experimental observations
      reported in the literature. They can also provide some useful guidelines for
      optimizing the mechanical performance of dental composite restorations. The
      compliance ratio, a new parameter derived from the model, represents a fuller
      description of the constraints of the system.

PMID- 24029103
TI  - Fit to be tied.

PMID- 24029102
TI  - Lesser accidental arterial catheter removal with the femoral access than with the
      cubital, dorsalis pedis and brachial arterial accesses.

PMID- 24029104
TI  - Seclusion room vs. physical restraint in an adolescent inpatient setting:
      patients' attitudes.
AB  - BACKGROUND: The use of physical restraints or a seclusion room for the treatment
      of adolescents in a psychiatric inpatient setting raises ethical dilemmas. We
      investigated the attitudes of adolescents towards these two means of confinement.
      METHOD: We used a structured questionnaire to collect data on the attitudes of 50
      adolescent patients, hospitalized in a closed psychiatric ward, towards the use
      of physical restraint versus a seclusion room. RESULTS: Seventy per cent of the
      participants in the study preferred seclusion in the seclusion room over bed
      restraint, whereas 22% preferred physical restraint. Eighty-two percent described
      seclusion in the seclusion room as less frightening than restraint. Seventy-four
      per cent reported that seclusion in the seclusion room improved their mental
      state to a larger extent than restraint. The inpatient adolescents reported
      feeling the time they needed to reach a state of calm was shorter when they were
      confined to the seclusion room than when they were physically restrained
      (p>.001). CONCLUSIONS: The use of a seclusion room may be preferable compared to
      physical restraint for inpatient adolescents.

PMID- 24029105
TI  - Commentary: can seclusion and restraint be person-centered?

PMID- 24029106
TI  - Voting of hospitalized and ambulatory patients with mental disorders in
      parliamentary elections.
AB  - The authors examined the voting rate among psychiatric inpatients and the voting
      rate of outpatients, in relation to the severity of their illness. On election
      day the number of inpatients that voted was recorded in one psychiatric hospital
      in Israel. For two weeks following the elections outpatients were asked if they
      voted: 100/271 (36.9%) inpatients and 131/181(72.4%) ambulatory patients voted;
      53.8% of the inpatients and 4.7% of the ambulatory patients could not vote
      because they had no identity cards. Ambulatory patients with no prior
      hospitalizations had the highest voting rates. The most common reason for not
      voting among inpatients in Israel is lack of identity cards.

PMID- 24029107
TI  - Dissociative symptoms as a consequence of traumatic experiences: the long-term
      effects of childhood sexual abuse.
AB  - BACKGROUND: The purpose of this study was to assess the prevalence of
      dissociative symptoms and post-traumatic experiences in an ambulatory setting.
      METHOD: The study was conducted in the ambulatory outpatient clinic of the
      Beersheva Mental Health Center. Over a period of six months new patients over 18
      years of age were asked to participate in this survey. Patients completed
      questionnaires including the Dissociative experience Scale, trauma History
      Questionnaire, impact of event Scale, and Post-traumatic Diagnostic Scale.
      RESULTS: A total of 505 patients were enrolled in the study, and 456 completed
      questionnaires were analyzed. of these, 442 (97%) participants reported at least
      one traumatic event during their lifetime. the traumatic events were experienced
      as meaningful and severe at the time of occurrence. the effects of sexual and
      childhood emotional abuse remained very intense throughout the victim's life and
      were viewed as powerful, significant experiences. on the other hand, traumatic
      experiences such as natural disasters and battle trauma were associated with
      longterm effects of relatively low intensity. CONCLUSIONS: The presence of
      undiagnosed posttraumatic stress disorder (PtSD) among patients in outpatient
      mental health clinics suggests that screening and diagnostic procedures for this
      condition be more carefully defined. our most important finding is the large
      impact of childhood trauma, especially sexual abuse, on later life. thus the
      prevention, early detection and treatment of child abuse in preventing long term
      psychopathology must be emphasized.

PMID- 24029108
TI  - Initial validation of the Russian version of the World Mental Health Structured
      Clinical Interview for DSM-IV.
AB  - BACKGROUND: The Structured Clinical Interview for DSMIV (SCID) is a highly
      reliable diagnostic instrument used worldwide. However, there is little data as
      to its reliability and validity outside of the U.S. OBJECTIVE: To create a
      Russian version of the World Mental Health (WMH) SCID and to test its validity
      among Russian Jewish emigres in the U.S. METHOD: The author, a bilingual Board
      Certified psychiatrist who has been trained in the application of the original
      English SCID and WMH SCID, supervised the translation and adaptation of the WMH
      SCID into Russian. A convenience sample, consisting of 35 subjects, was
      interviewed by two clinicians trained by the author, yielding 54 diagnoses. All
      interviews were audio taped and blindly reviewed by the author, who served as the
      gold standard. RESULTS: 32 subjects met criteria for one or more of 11 DSMIV
      depressive and anxiety disorder diagnoses. There was very good inter-rater
      agreement; median kappa was 0.75; seven disorders had kappas ranging from .65
      (Depressive Disorder Not Otherwise Specified) to 1.0 (dysthymia and agoraphobia).
      Sensitivity was 88.9% and specificity was 77.1 %, compared to the "gold standard"
      diagnosis. CONCLUSION: Initial data suggest that the Russian version of the WMH
      SCID is a valid instrument.

PMID- 24029109
TI  - Epigenetic transmission of Holocaust trauma: can nightmares be inherited?
AB  - The Holocaust left its visible and invisible marks not only on the survivors, but
      also on their children. Instead of numbers tattooed on their forearms, however,
      they may have been marked epigenetically with a chemical coating upon their
      chromosomes, which would represent a kind of biological memory of what the
      parents experienced. as a result, some suffer from a general vulnerability to
      stress while others are more resilient. Previous research assumed that such
      transmission was caused by environmental factors, such as the parents'
      childrearing behavior. New research, however, indicates that these
      transgenerational effects may have been also (epi) genetically transmitted to
      their children. Integrating both hereditary and environmental factors,
      epigenetics adds a new and more comprehensive psychobiological dimension to the
      explanation of transgenerational transmission of trauma. Specifically,
      epigenetics may explain why latent transmission becomes manifest under stress. a
      general theoretical overview of epigenetics and its relevance to research on
      trauma transmission is presented.

PMID- 24029110
TI  - Changes in heart rate variability before and after ECT in the treatment of
      resistant major depressive disorder.
AB  - BACKGROUND: In this study, we aimed to evaluate the effects of electroconvulsive
      therapy (ECT) on cardiac autonomic functions (CAF) in patients with major
      depressive disorder (MDD) using heart rate variability (HRV) analysis. METHOD:
      Fourteen men joined the study. Nine ECTs were administered. Holter monitoring was
      performed before treatment and at the end of the first, third and sixth weeks of
      the treatment. The Hamilton Depression Rating Scale (HAM-D) was used to assess
      symptom severity. RESULTS: Seven patients responded to ECT. There was a change of
      2-hour resting HF, pNN50 and RMSSD scores between week 0 and week 6. This change
      was not significant after week 1 and week 3. HRV values did not differ when we
      grouped the patients as responders and non-responders to ECT except the 2-hour
      resting HF value of responders between week 0 and week 6 and the 24-hour HF value
      of non-responders between week 1 and week 6. All observed changes showed a
      decrease in parameters. Overall, the LF/HF ratio did not change significantly in
      either analysis. HRV values did not correlate with HAM-D scores and no relation
      was found between treatment response and HRV analysis. After Benferroni
      adjustment none of the changes were found statistically significant. LIMITATIONS:
      The limitations of the study are the small sample size and the absence of healthy
      controls. CONCLUSIONS: A consistent change in HRV was not observed in response to
      ECT in patients with MDD. Accepting the HRV as a promising surrogate marker of
      autonomic activity, ECT does not cause a significant change in nine male
      treatment resistant MDD patients cardiac autonomic functions.

PMID- 24029111
TI  - Correlates of physical activity with intrusive thoughts, worry and impulsivity in
      adults with attention deficit/hyperactivity disorder: a cross-sectional pilot
      study.
AB  - BACKGROUND: Physical exercise is known to produce numerous psychological
      beneficial effects in healthy and clinical populations. Nevertheless, little is
      known about the relationship between exercise and ADhD symptoms, let alone among
      adults with ADhD. this study examines the association between exercise and three
      ADhD symptoms: (1) behavioral impulsivity; (2) intrusive unwanted thoughts and
      (3) worry. the latter two are cognitive facets of anxiety, a prominent symptom of
      ADhD. METHODS: Physical activity was measured using a selfreport questionnaire.
      thirty participants with a diagnosis of ADhD were divided into two groups:
      Participants engaging in frequent aerobic activity ("high activity" group), and
      participants engaging in non-frequent physical activity ("low activity" group).
      RESULTS: Adults with ADhD engaging in frequent aerobic physical activity report
      significantly less behavioral impulsivity and experience significantly less
      worrisome and intrusive thoughts. CONCLUSIONS: Our results reflect an association
      between physical activity and reduced symptoms of impulsivity and intrusive and
      worrisome thoughts in an adult ADhD sample. the results of this pilot study may
      encourage further investigations emphasizing the causal link between physical
      activity and ADhD symptoms. Suggested underlying neurobiological mechanisms,
      clinical implications and limitations are discussed.

PMID- 24029112
TI  - Analysis of quality of life and anxiety in patients with different forms of
      epilepsy.
AB  - BACKGROUND: Anxiety symptoms may have significant implications on the quality of
      life of patients with epilepsy. The aim of our research is a comparative analysis
      of the quality of life, i.e., of the level of disability in patients with
      different forms of epilepsy. METHOD: In this cross-sectional study, the sample
      consisted of three groups of 30 patients each--with recently diagnosed
      generalized epilepsy, temporal and extratemporal epilepsy. the anxiety level in
      these groups was compared with the control group of 30 healthy subjects. Beck
      anxiety inventory (Bai) was used for assessment of anxiety. level of functional
      disability due to anxiety was measured according to the Sheehan Disability Scale
      (SDS). RESULTS: Patients with extratemporal epilepsy had the greatest level of
      functional disability, while patients with generalized epilepsies had the lowest
      average of scores on the Sheehan scale. the correlation between the Bai and the
      SDS was highly statistically significant. CONCLUSIONS: Our results clearly
      indicate the need for a broader concept of therapy--neurological (antiepileptic
      therapy) and psychiatric (pharmaco-, psycho- and social therapy) when it comes to
      anxiety in patients with epilepsy.

PMID- 24029113
TI  - Recalling the threat: dental anxiety in patients waiting for dental surgery.
AB  - OBJECTIVE: The tendency of patients with high levels of anxiety to easily recall
      threatening stimuli has not been examined in relation to dental anxiety. The
      current study was aimed to examine the effect of pre-treatment anxiety levels and
      of information given prior to dentistry surgical procedures on free recall of
      threatening words. METHODS: Forty-two subjects attending a private dental clinic
      were recruited. While awaiting root-canal treatment or tooth extraction, patients
      were asked to proofread a list of 32 words, which contained mental and physical
      threat-related words, as well as positive and neutral words. only half of the
      subjects received information on the forthcoming surgical procedure. Pre
      treatment anxiety levels using the dental anxiety Scale (daS) and word recall
      were evaluated. RESULTS: Only subjects with high dental anxiety (above median
      score) recalled more mental and physical threat related words, than positive
      words. Moreover, the dental anxiety score as a continuous variable predicted the
      mean number of mental threat-related words recalled. no significant differences
      were noted between those who did or did not receive information prior to the
      surgical procedures, on the recall of the four types of words. CONCLUSIONS:
      Similar to other anxiety disorders, patients with dental anxiety display a
      tendency for free recall of threatening stimuli presented to them before a
      threatening event. Preliminary information given prior to dentistry surgical
      procedures does not decrease anxiety. Suggestions for intervention in the
      dentist's clinic are given.

PMID- 24029114
TI  - Cultural psychiatry in Tel Aviv: how relevant!
AB  - The First Mediterranean Conference on Cultural Psychiatry took place in Tel Aviv,
      Israel. This conference was a great success. With about 200 participants, mostly
      from Israel but with also 46 participants coming from 13 other countries:
      Mediterranean countries, Europe, North America and Australia. It contained three
      intensive days of plenary lectures and symposia, and a very impressive film,
      "Waltz with Bashir". The proceedings included 88 lectures, and there were 8
      posters, which meant that nearly half of the attending persons were giving a
      lecture, as is always the case in real scientific conferences. Four parallel
      programs were running at the same time, which made it very difficult to choose
      which to attend. Inevitably, this report reflects only a part of the conference. 

PMID- 24029115
TI  - HIV-derived lentiviral particles promote T-cell independent activation and
      differentiation of naive cognate conventional B2-cells in vitro.
AB  - In animal models, lentiviral particles (LP) were shown to be promising HIV
      vaccine candidates. Since little is known about the direct impact of LP on
      antigen-specific B cells, we incorporated Hen Egg Lysozyme (HEL) into LP (HEL-LP)
      derived from HIV to study their effect on HEL-specific, B cell receptor
      transgenic B-cells (HEL(+)B-cells) in vitro. We observed preferential binding of
      HEL-LP to HEL(+)B-cells and their efficient internalization. HEL-LP were able to
      effectively cross-link B-cell receptors as indicated by the loss of surface
      CD62L. In the absence of CD4(+) T-cells, other activation events induced by LP in
      cognate naive B-cells included increased expression of activation and co
      stimulatory molecules as well as an enhanced proliferative response.
      Additionally, the B-cell phenotype shifted toward a germinal center pattern with
      further differentiation into memory and IgG3- and IgA-producing cells. The
      observed CD4(+) T-cell independent activation and differentiation may be due to
      LP-induced expression of CD40L by a subset of cognate B-cells. Thus, even in the
      absence of CD4(+) T-cells LP provide strong direct activation signals to cognate
      naive B-cells, which may contribute to the strong humoral immune responses
      observed after LP immunization. 

PMID- 24029116
TI  - Adolescents and vaccines in the western world.
AB  - Recent data have shown that the immune protection evoked by vaccines given in the
      first years of life progressively weakens, and that this is associated with a
      higher than expected incidence of vaccine-preventable diseases in adolescents and
      young adults. Furthermore, the greater circulation of pathogens among adolescents
      and young adults leads to a high risk of infection in unvaccinated or not fully
      vaccinated younger children. These findings, together with the availability of
      vaccines specifically developed to prevent infections that typically occur during
      adolescence, have induced a number of experts to suggest radical changes in the
      immunisation schedules usually recommended by health authorities. The most
      important of these relate pertussis, meningococcal and human papillomavirus
      vaccines but, although they are based on unexceptionable scientific premises, the
      suggestions have been only slowly and partially received in most countries, even
      in those in which vaccination programmes are usually adequately implemented and
      monitored. Adolescence is a particular period of life characterised by changes in
      intellectual, moral, physical, emotional and psychological development. All of
      these can have a considerable impact on compliance with immunisation schedules
      because the approach to any preventive method no longer entirely depends on
      parents' and pediatricians' judgements as in the first years of life but is the
      consequence of a more complex process involving the adolescents' thoughts and
      opinions, their relationships with their parents, friends and physicians, and the
      information they receive from the mass media. Every effort should be made to
      overcome the barriers to adolescent immunisation, including those arising from
      the adolescents themselves. 

PMID- 24029117
TI  - "HPV? Never heard of it!": a systematic review of girls' and parents' information
      needs, views and preferences about human papillomavirus vaccination.
AB  - BACKGROUND AND OBJECTIVE: Two human papillomavirus vaccines were licenced in
      2006/2007 for cervical cancer prevention. National vaccination programmes for
      schoolgirls were subsequently introduced in some European countries, North
      America and Australia. To understand factors influencing vaccine uptake and to
      inform the development of appropriate UK educational materials, we aimed to
      synthesise evidence of girls' and parents' information needs, views and
      preferences regarding HPV vaccination. DESIGN: Systematic review and mixed method
      synthesis of qualitative and survey data. DATA SOURCES: Twelve electronic
      databases; bibliographies of included studies 1980 to August 2011. REVIEW
      METHODS: Two reviewers independently screened papers and appraised study quality.
      Studies were synthesised collaboratively using framework methods for qualitative
      data, and survey results integrated where they supported, contrasted or added to
      the themes identified. RESULTS: Twenty-eight qualitative studies and 44 surveys
      were included. Where vaccination was offered, uptake was high. Intention to
      decline was related to a preference for vaccinating later to avoid appearing to
      condone early sexual activity, concerns about vaccine safety and low perception
      of risk of HPV infection. Knowledge was poor and there were many misconceptions;
      participants tried to assess the potential benefits and harms of vaccination but
      struggled to interpret limited information about HPV in the context of existing
      knowledge about sexually transmitted infections and cancer. Conclusion Many girls
      and their parents have limited understanding to an extent that impinges on their
      ability to make informed choices about HPV vaccination and could impact on future
      uptake of cervical screening. This is a considerable challenge to those who
      design and provide information, but getting the messages right for this programme
      could help in developing patient information about other HPV related cancers.

PMID- 24029118
TI  - Chronic neutrophilic leukaemia.

PMID- 24029119
TI  - Endings and beginnings at JNCCN.

PMID- 24029120
TI  - EGFR-mutated lung cancer with T790M-acquired resistance in the brain and
      histologic transformation in the lung.
AB  - This case report describes the rare occurrence of a T790M resistance mutation
      found in a central nervous system (CNS) parenchymal metastasis. A concomitant
      squamous histology transformation in a lung non-T790M-resistant metastasis is
      also described. The authors hypothesize that this CNS resistance and histology
      transformation may have resulted from intermittent use of erlotinib treatment.
      This case report emphasizes the complexities of using erlotinib in the induction
      setting. 

PMID- 24029121
TI  - Acute myeloid leukemia, version 2.2013.
AB  - These NCCN Guidelines Insights summarize several key updates to the NCCN
      Guidelines for Acute Myeloid Leukemia and discuss the clinical evidence that
      support the recommendations. The updates described in this article focus on the
      acute promyelocytic leukemia (APL) section, featuring recommendations for
      additional induction/consolidation regimens in patients with low- or intermediate
      risk APL, and providing guidance on maintenance strategies for APL. 

PMID- 24029122
TI  - Breast cancer in adolescents and young adults: a review with a focus on biology.
AB  - Breast cancer is a substantial contributor to adolescent and young adult (AYA)
      malignancies, defined as a diagnosis of cancer between the ages of 15 and 39. In
      the United States, 6.6% of breast cancer cases are diagnosed among women younger
      than 40 years. When breast cancer occurs in AYAs, it typically has a worse
      prognosis and more-aggressive phenotype; higher proportions of high-grade and
      later-stage tumors; lower estrogen receptor positivity; and, in some studies,
      higher expression of HER2. Age-specific differences in the biology of AYA breast
      cancer have been explored in large-scale genomic studies with mixed results.
      Although some studies suggest that AYA breast cancer has a unique biology, others
      have shown that its aggressive nature is the result of higher frequencies of
      aggressive breast cancer subtypes among younger patients. More recently, stromal
      related gene signatures have shown prognostic significance in AYA breast cancer,
      suggesting that differences in microenvironment may account for age-specific
      differences in breast cancer behavior. Although general principles for selecting
      cytotoxic and targeted agents are similar between AYAs and the general breast
      cancer population, endocrine therapy choices in the adjuvant and metastatic
      settings vary by pre- and postmenopausal status. The role of ovarian suppression
      remains controversial and is reviewed. The AYA population is a unique group of
      patients who need individualized care, including considerations of hereditary
      breast cancer predispositions, future fertility, and the effect of therapy on
      immediate and long-term quality of life, all of which require coordinated
      multidisciplinary care. This article addresses the epidemiology, genetics, and
      management of breast cancer in AYA women and highlights unique medical issues
      important to this population. 

PMID- 24029123
TI  - A time study of cancer genetic counselors using a genetic counselor-only patient
      care model versus a traditional combined genetic counselor plus medical
      geneticist care model.
AB  - Analyses of time-based effort have determined that clinical genetic services are
      labor-intensive, although these data derive primarily from studying geneticists'
      efforts in the pediatric model. No studies have investigated the time and patient
      care activities of cancer genetic counselors (GCs) in traditional clinics with a
      medical geneticist (GC/MD) compared with genetic counselor-only (GCO)
      appointments. In this study, 6 GCs prospectively tracked time spent in patient
      care activities in both clinical settings. The authors found that overall, GCs'
      time spent per patient was lower for GCO versus GC/MD visits. No differences were
      seen in time spent on results disclosure, but differences were noted in case
      preparation, face-to-face, and follow-up times. Furthermore, no differences were
      seen in number of case preparation activities or topics covered during a session.
      These data suggest that GCO visits result in better use of GCs' time, without a
      trade-off in number of patient-related activities. 

PMID- 24029124
TI  - Study using the NCCN guidelines for palliative care to screen patients for
      palliative care needs and referral to palliative care specialists.
AB  - The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for
      Palliative Care recommend screening all patients for palliative care (PC) needs
      and to call a PC consult when referral criteria are met. The goal of this pilot
      project was to evaluate the feasibility of implementing the screening and
      referral components of the NCCN Guidelines for Palliative Care in patients
      admitted to the Gastrointestinal Oncology Service (GIOS) at a comprehensive
      cancer center (CCC). Floor nurses performed the initial screening of all patients
      admitted to the 2 teams-Team A and Team B-of the GIOS on one floor of Memorial
      Hospital for 3 months. In addition, only the patients admitted to Team A were
      evaluated according to the referral criteria, triggering a PC consult if results
      were positive. Nurses were surveyed regarding satisfaction with and the
      acceptability of screening. During the study period, 229 (90%) total admissions
      were screened, with 169 (73%) having positive results. Of the Team A admissions,
      72 (64%) met the referral criteria. More consults occurred for patients in Team A
      (47 vs 15; P=.001). In 30% of the referral criteria-triggered consults, the PC
      needs were manageable by the primary team. Nurses reported screening to be easy
      and quick (<5 minutes per patient) but only somewhat helpful. Being unfamiliar
      with many patients and families, floor nurses often felt unable to screen them
      accurately for some issues. In conclusion, screening was feasible, increasing
      access to PC, but accuracy and usefulness are concerns. With a consult indicated
      in 64% patients, yet with 30% being manageable by the primary team, the current
      criteria may be too sensitive for the inpatient environment of a CCC. More
      evaluation is needed before widespread implementation can be recommended. 

PMID- 24029125
TI  - Therapeutic delays lead to worse survival among patients with hepatocellular
      carcinoma.
AB  - Although prior studies have shown underuse of appropriate therapy in patients
      with hepatocellular carcinoma (HCC), no studies to date have assessed the
      prevalence and clinical impact of therapeutic delays among patients with HCC. The
      goal of this study was to characterize and identify factors associated with
      underuse and delays in treatment of these patients. A retrospective cohort study
      was conducted of patients with cirrhosis diagnosed with HCC at a large urban
      safety net hospital between January 2005 and June 2012. Dates for HCC diagnosis
      and any treatments were recorded. Univariate and multivariate analysis was used
      to determine factors associated with treatment underuse and delayed treatment,
      which was defined as time from diagnosis to treatment exceeding 3 months. The
      authors identified 267 treatment-eligible patients with HCC, of whom only 62%
      received HCC therapy. On multivariate analysis, tumor stage (odds ratio [OR],
      0.48; 95% CI, 0.36-0.65), Child-Pugh class (OR, 0.49; 95% CI, 0.28-0.84), and
      black race (OR, 0.55; 95% CI, 0.31-0.99) were associated with lower rates of
      treatment use. The median time to treatment was 1.7 months, with 31% of patients
      experiencing delayed treatment. Delayed treatment was associated with the
      presence of ascites (hazard ratio [HR], 2.8; 95% CI, 1.3-6.1) and current
      treatment with transarterial chemoembolization (HR, 4.8; 95% CI, 1.8-12.5). After
      adjusting for tumor stage and Child-Pugh class, treatment underuse (HR, 0.33; 95%
      CI, 0.24-0.46) and delayed treatment (HR, 0.50; 95% CI, 0.30-0.84) were both
      associated with significantly worse survival. Results showed that, in addition to
      one-third of patients not receiving HCC-directed therapy, another 30% experienced
      significant therapeutic delays, leading to worse survival. 

PMID- 24029127
TI  - Clinical discussion and review of the management of brain metastases.
AB  - Brain metastases are common in patients with cancer and are associated with a
      poor prognosis. Optimal treatment requires an integrative multidisciplinary
      approach, and therapeutic options may include stereotactic radiosurgery, whole
      brain radiation therapy, surgical resection, chemotherapy, and targeted agents.
      The goals of therapy are to prolong survival, preserve neurologic function, and
      palliate symptoms. This article outlines the various therapeutic modalities,
      factors that guide treatment decisions, and medical management of frequently
      encountered complications of brain metastases. 

PMID- 24029128
TI  - Controversies in the treatment of elderly patients with newly diagnosed
      glioblastoma.
AB  - Approximately half of all patients with glioblastoma are older than 65 years and
      nearly one-quarter are older than 70 years, with a rising incidence of this
      disease in the elderly population. The life expectancy of elderly patients with
      glioblastoma is significantly shorter than in younger patients. Potential
      explanations for this abbreviated survival include differences in tumor biology,
      reduced use of therapies, enhanced toxicity of treatment, or diminished efficacy
      of available therapies with increasing age. The current standard treatment of
      newly diagnosed, protocol-eligible, nonelderly patients with glioblastoma is
      based on the randomized prospective EORTC/NCIC study that included patients aged
      18 to 70 years with a performance status of ECOG 0 to 2. Limited single
      institution retrospective series suggest that clinically fit elderly patients may
      benefit from a similar treatment regimen. However, no randomized trial has been
      performed in the elderly population using this regimen. Available prospective
      randomized clinical trials in the elderly population with glioblastoma have shown
      that radiotherapy is superior to supportive care only, that single-modality
      hypofractionated radiotherapy (reduced dose and shorter treatment schedule) is an
      alternative to single-modality standard fractionated radiotherapy, and that
      single-agent temozolomide is equivalent to radiotherapy alone. This article
      summarizes published data of current patterns of care in elderly patients and
      reviews published evidence as it pertains to the benefit of different treatment
      modalities in elderly patients with glioblastoma. Notwithstanding the previously
      mentioned randomized trials, the optimal treatment of elderly patients with
      glioblastoma remains controversial. 

PMID- 24029129
TI  - Evolving policy issues in oncology: revisiting biosimilars and molecular testing.

PMID- 24029131
TI  - NCCN Guidelines(R) Updates.

PMID- 24029126
TI  - Central nervous system cancers.
AB  - Primary and metastatic tumors of the central nervous system are a heterogeneous
      group of neoplasms with varied outcomes and management strategies. Recently,
      improved survival observed in 2 randomized clinical trials established combined
      chemotherapy and radiation as the new standard for treating patients with pure or
      mixed anaplastic oligodendroglioma harboring the 1p/19q codeletion. For
      metastatic disease, increasing evidence supports the efficacy of stereotactic
      radiosurgery in treating patients with multiple metastatic lesions but low
      overall tumor volume. These guidelines provide recommendations on the diagnosis
      and management of this group of diseases based on clinical evidence and panel
      consensus. This version includes expert advice on the management of low-grade
      infiltrative astrocytomas, oligodendrogliomas, anaplastic gliomas, glioblastomas,
      medulloblastomas, supratentorial primitive neuroectodermal tumors, and brain
      metastases. The full online version, available at NCCN. org, contains
      recommendations on additional subtypes. 

PMID- 24029132
TI  - After repeated division, bone marrow stromal cells express inhibitory factors
      with osteogenic capabilities, and EphA5 is a primary candidate.
AB  - The differentiation capability of human bone marrow stromal cells (hBMSCs) is
      thought to deteriorate over multiple doubling processes. To clarify the
      deterioration mechanisms, the multilineage differentiation capabilities of short-
      and long-term passaged BMSCs were compared. Predictably, long-term passaged BMSCs
      showed reduced differentiation capacities compared to short-term passaged cells.
      Furthermore, a non-human primate heterotopic bone formation model demonstrated
      that long-term passaged BMSCs have bone formation capabilities but also exert
      inhibitory effects on bone formation. This finding indicated that long-term
      passaged BMSCs express higher levels of inhibitory factors than short-term
      passaged BMSCs do. Co-culture assays of short- and long-term passaged BMSCs
      suggested that the inhibitory signals required cell-cell contact and would
      therefore be expressed on the cell membrane. A microarray analysis of BMSCs
      identified ephrin type-A receptor 5 (EphA5) as an inhibitory factor candidate.
      Quantitative PCR revealed that among all members of the ephrin and Eph receptor
      families, only the expression of EphA5 was increased by BMSC proliferation. A
      gene knockdown analysis using siRNAs demonstrated that knockdown of EphA5 gene
      expression in long-term passaged BMSCs led to an increase in ALP mRNA expression.
      These results indicate that EphA5 may be a negative regulator of bone formation.
      A better understanding of the roles of the ephrin and Eph receptor families in
      hBMSCs may lead to alternative approaches for manipulating hBMSC fate. In
      addition, this avenue of discovery may provide new therapeutic targets and
      quality-control markers of the osteogenic differentiation capabilities of hBMSCs.

PMID- 24029133
TI  - Moving forward after YODA.

PMID- 24029134
TI  - When money talks.

PMID- 24029135
TI  - Black, white, or gray: how different (or similar) are YODA and the The Spine
      Journal reviews of BMP-2?

PMID- 24029136
TI  - Appropriate use of satisfaction scores in spine care.

PMID- 24029137
TI  - Reduction of surgical site infection in spine surgery: an opportunity for quality
      improvement and cost reduction.

PMID- 24029138
TI  - Clinical sequelae after rhBMP-2 use in a minimally invasive transforaminal lumbar
      interbody fusion.
AB  - BACKGROUND CONTEXT: Recent reports of postoperative radiculitis, bone osteolysis,
      and symptomatic ectopic bone formation after recombinant human bone morphogenetic
      protein-2 (rhBMP-2) use in transforaminal lumbar interbody fusions (TLIFs) are a
      cause for concern. PURPOSE: To determine the clinical and radiographic
      complications associated with BMP utilization in a minimally invasive
      transforaminal lumbar interbody fusion (MIS-TLIF) environment. STUDY
      DESIGN/SETTING: Retrospective clinical case series at a single institution.
      PATIENT SAMPLE: Five hundred seventy-three consecutive patients undergoing an MIS
      TLIF. OUTCOME MEASURES: Reoperation rates and total costs associated with
      complications of rhBMP-2 use and pseudarthrosis. METHODS: A retrospective review
      of 610 consecutive patients undergoing an MIS-TLIF (2007-2010) by a single
      surgeon at our institution was performed (mean age 48.7 years, range 26-82
      years). All patients underwent an MIS laminectomy with bilateral facetectomy,
      single TLIF cage, unilateral pedicle screw fixation, and 12 mg (large kit) or 4.2
      mg (small kit) of rhBMP-2. The BMP-2 collagen-soaked sponge was placed anteriorly
      in the disc space, followed by local bone graft, and then the cage was filled
      only with local bone and no BMP-2. Patients were evaluated at 6 months and 1 year
      with computed tomography (CT) scan. Those demonstrating neuroforaminal bone
      growth, osteolysis/cage migration, or pseudarthrosis were reviewed, and cost data
      including direct cost/procedure for both index and revision surgeries were
      collected. RESULTS: Of the 573 patients, 10 (1.7%) underwent 15 additional
      procedures based on recalcitrant radiculopathy and CT evidence of neuroforaminal
      bone growth, vertebral body osteolysis, and/or cage migration. Thirty-nine
      patients (6.8%) underwent reoperation for clinically symptomatic pseudarthrosis.
      Bone overgrowth was associated with nerve impingement and radiculopathy in all 10
      patients (small kit, n=9; large kit, n=1). Osteolysis and cage migration occurred
      in 2 (20%) of these same 10 patients. Average total costs were calculated per
      procedure ($19,224), and the costs for reoperation equaled $14,785 per encounter
      for neuroforaminal bone growth and $20,267 for pseudarthrosis. CONCLUSIONS:
      Symptomatic ectopic bone formation, vertebral osteolysis, and pseudarthrosis are
      recognized complications with the use of rhBMP-2 in MIS-TLIFs. Potential causes
      include improper dosage and a closed space that prevents the egress of the
      postoperative BMP-2 fluid collection. Management of these complications has a
      substantial cost for the patient and the surgeon and needs to be considered with
      the off-label use of rhBMP-2.

PMID- 24029139
TI  - Assessment of patient's pain-related behavior at physical examination may allow
      diagnosis of recent osteoporotic vertebral fracture.
AB  - BACKGROUND CONTEXT: Although innumerable studies have analyzed the multiple
      aspects of osteoporotic vertebral fractures, no study has focused on the clinical
      features related to spine pain in patients with recent osteoporotic vertebral
      compression fractures (VCFs). PURPOSE: To determine whether the assessment of
      pain-related behavior (P-RB) of patients with osteoporotic VCFs of recent onset
      may allow the fracture to be strongly suspected, or even diagnosed, at physical
      examination. STUDY DESIGN: Pain-related behavior of elderly patients attending an
      outpatient spine clinic was evaluated on the basis of six consecutive movements
      made on the examining table. PATIENT SAMPLE: Fifty-six patients complaining only
      of lumbar or thoracic pain. The fractured patients (FPs), representing the
      fracture group (FG), were the 19 who had a recent VCF, whereas the control group
      (CG) consisted of the remaining 37 patients. METHODS: Assessment of P-RB was
      based on six parameters: grimacing, sighing, clenching or blocking eyelids,
      gaping or strongly tightening the lips, need for help to take positions, and
      extreme difficulty to turn in the prone position. A score of 1 or a decimal was
      assigned to each parameter, the final score to each patient being 0 to 6. Three
      types of injury, acute (I), subacute (II), or chronic (III), were identified on
      the basis of the time elapsed from the probable occurrence of the fracture. The
      diagnosis of recent fracture was based on magnetic resonance images. Patients
      were videotaped during their movements. An examiner, unaware of the clinical
      history and diagnosis, gave a P-RB score to all patients and indicated whether
      they had to be placed in FG or CG, and also their presumable type of fracture.
      Subsequently, a DVD with the videotapes of all patients was given to three
      independent examiners, not specifically expert of spine conditions, who were
      asked to make the same evaluations as the first examiner. RESULTS: The mean
      scores for P-RB given by the first examiner were 4.6 to FG and 0.7 to CG (p<.01).
      He identified as FPs 89% of those who were in FG. The type of fracture was
      indicated correctly in 88% of patients identified as FPs. The mean scores for the
      three types of fracture ranged from 5.4 (Type I) to 3.3 (Type III) (p<.001). The
      mean scores for P-RB given by the independent examiners to FG and CG were similar
      to those of the first examiner. The rates of correctness in identifying the type
      of fracture in patients indicated as FPs varied from 87% to 80%. The mean scores
      assigned to the patients included in the three types of fracture ranged from 5.4
      to 2.8. CONCLUSIONS: Pain-related behavior evaluation of patients with
      osteoporotic VCF during their movements on the examining table may allow to
      suspect, or even diagnose, the presence of a fracture, particularly in the
      initial 4 to 6 weeks after the occurrence. Even orthopedic surgeons not
      particularly familiar with spine care may be able to suspect the injury during
      physical examination.

PMID- 24029140
TI  - 228Ra/226Ra ratio and 7Be concentration in the Sea of Japan as indicators for
      water transport: comparison with migration pattern of Fukushima Dai-ichi NPP
      derived 134Cs and 137Cs.
AB  - To assess the migration patterns of radiocesium emitted from the Fukushima Dai
      ichi Nuclear Power Plant (FDNPP), we analyzed (228)Ra/(226)Ra ratios and (7)Be
      concentrations and compared them with (134)Cs and (137)Cs concentrations in
      seawater samples collected within the Sea of Japan before and after the FDNPP
      accident (i.e., during the period 2007-2012) using low-background gamma
      spectrometry. The (228)Ra/(226)Ra ratios in surface waters exhibited lateral and
      seasonal variations, reflecting the flow patterns of surface water. This
      indicates the transport patterns of the FDNPP-derived radiocesium by surface
      water. Cosmogenic (7)Be (half-life: 53.3 d) exhibited markedly high
      concentrations (5-10 mBq/L) at depths shallower than 50 m, with concentrations
      decreasing steeply (0.2-2 mBq/L) at depths of 50-250 m. The distribution of (7)Be
      concentrations suggests that the downward delivery of the FDNPP-derived
      radiocesium to below 50 m depth was negligible for a few months prior to its
      removal from the Sea of Japan.

PMID- 24029141
TI  - [Cubital tunnel syndrome: a retrospective review of 55 subcutaneous
      transpositions with minimum 3-year follow-up].
AB  - The surgical management of the cubital tunnel syndrome has no strict rules to
      follow. Surgical treatments are various, but none of them has been shown to be
      superior to the others. This retrospective study presents the clinical results in
      73 patients who underwent an anterior subcutaneous transposition of the ulnar
      nerve, between January 2000 and January 2010, with a minimum 3-year follow-up.
      Fifty-five patients were assessed with an average follow-up of 65.7 months.
      McGowan grading system as modified by Goldberg was used to analyse clinical
      results, preoperatively and at follow-up. The DASH score was used to assess
      physical function. The average preoperative evolution of symptoms was 16.7
      months, and mean period to resolution was 4.7 months. The grade in McGowan
      grading system as modified by Goldberg significatively improved at follow-up
      (P=0.0002). Only five patients kept paresthesia. The mean postoperative DASH
      score was 7.27/100. The satisfaction rate was 96%, and all the patients except
      one returned back to their occupation. There was neither infection nor complex
      regional pain syndrome. The anterior subcutaneous transposition leads to very
      good clinical results, satisfaction and physical function. It is an effective
      surgical method, without complication in our study, which gives long-term
      results. 

PMID- 24029143
TI  - beta-Arrestins 1 and 2 are critical regulators of inflammation.
AB  - beta-Arrestins 1 and 2 couple to seven trans-membrane receptors and regulate G
      protein-dependent signaling, receptor endocytosis and ubiquitylation. Recent
      studies have uncovered several unanticipated functions of beta-arrestins,
      suggesting that the role of beta-arrestins in cell signaling is much broader than
      originally thought. It is now recognized that beta-arrestins can transduce
      receptor signaling independent of G proteins. The expression of beta-arrestins is
      differentially regulated in immune cells and tissues in response to specific
      inflammatory stimuli, and beta-arrestins are critical regulators of the
      inflammatory response. This review will focus on beta-arrestins in immune cells
      and the impact of altered expression on the pathogenesis of specific inflammatory
      diseases. Understanding the role of beta-arrestins in inflammation may lead to
      new strategies to treat inflammatory diseases, such as sepsis, rheumatoid
      arthritis, asthma, multiple sclerosis, inflammatory bowel disease and
      atherosclerosis. 

PMID- 24029142
TI  - Induction of homologous recombination following in utero exposure to DNA-damaging
      agents.
AB  - Much of our understanding of homologous recombination, as well as the development
      of the working models for these processes, has been derived from extensive work
      in model organisms, such as yeast and fruit flies, and mammalian systems by
      studying the repair of induced double strand breaks or repair following exposure
      to genotoxic agents in vitro. We therefore set out to expand this in vitro work
      to ask whether DNA-damaging agents with varying modes of action could induce
      somatic change in an in vivo mouse model of homologous recombination. We exposed
      pregnant dams to DNA-damaging agents, conferring a variety of lesions at a
      specific time in embryo development. To monitor homologous recombination
      frequency, we used the well-established retinal pigment epithelium pink-eyed
      unstable assay. Homologous recombination resulting in the deletion of a
      duplicated 70 kb fragment in the coding region of the Oca2 gene renders this gene
      functional and can be visualized as a pigmented eyespot in the retinal pigment
      epithelium. We observed an increased frequency of pigmented eyespots in resultant
      litters following exposure to cisplatin, methyl methanesulfonate, ethyl
      methanesulfonate, 3-aminobenzamide, bleomycin, and etoposide with a contrasting
      decrease in the frequency of detectable reversion events following camptothecin
      and hydroxyurea exposure. The somatic genomic rearrangements that result from
      such a wide variety of differently acting damaging agents implies long-term
      potential effects from even short-term in utero exposures.

PMID- 24029144
TI  - Identification and functional characterization of a new IL-1 family member, IL
      1Fm2, in most evolutionarily advanced fish.
AB  - The IL-1 family consists of 11 members that play an important role as key
      mediators in inflammation and immunity. Here, we report the identification of a
      new member of the IL-1 family (IL-1Fm2) that is present in species belonging to
      the most evolutionarily advanced group of teleost fish (Series Percomorpha),
      including Perciformes, Beloniformes, Gasterosteiformes, Cyprinodontiformes and
      Pleuronectiformes. However, IL-1Fm2 seems to be absent in Tetraodontiformes,
      which also belong to the Percomorpha. The expression pattern of gilthead seabream
      IL-1Fm2 revealed that although it was hardly induced by PAMPs, the combination of
      PAMPs and recombinant IL-1Fm2 synergistically induced its expression in
      macrophages and granulocytes. In addition, recombinant IL-1Fm2 was able to
      activate the respiratory burst of seabream phagocytes and to synergistically
      induce the expression of IL-1beta, TNF-alpha, IL-8 and IL-10 when combined with
      PAMPs. Finally, although gilthead seabream IL-1Fm2 did not show a conserved
      caspase-1 processing site, macrophages processed IL-1Fm2 before being released.
      However, both pan-caspase and caspase-1 inhibitors failed to inhibit the
      processing and release of IL-1Fm2. These results demonstrate an important role of
      IL-1Fm2 in the regulation of fish immune responses, shed light on the evolution
      of the IL-1 family in vertebrates and point to the complexity of this cytokine
      family. 

PMID- 24029146
TI  - Nerve damage in leprosy: a continuing challenge to scientists, clinicians and
      service providers.
AB  - This review focuses on nerve damage in leprosy. We present evidence to support
      the argument that leprosy is best seen as a chronic neurological condition rather
      than a simple skin disease. Nerve damage affects small dermal nerves and
      peripheral nerve trunks. Perineural inflammation is a characteristic and hallmark
      of early leprosy. T cell-mediated inflammation is the main pathological process
      in leprosy nerve damage. The level of nerve damage in leprosy is high with up to
      60% of multibacillary patients having clinically apparent nerve damage at the
      time of diagnosis; 30% of patents may develop further nerve damage during
      treatment and 10% may develop new nerve damage after drug treatment. Since the
      nerve damage is immune mediated, the antibiotics used to treat Mycobacterium
      leprae infection have little effect on the accompanying nerve damage. This
      requires treatment with immunosuppressants to stop the inflammation. Treatment of
      nerve damage with steroids can be effective but about 50% of patients relapse and
      require a further course of steroids. Research is needed to refine steroid
      regimens to be used and define appropriate alternatives. Neuropathic pain is now
      being recognised as another late complication for leprosy patients. There are
      also service challenges relating to how best to identify patients who need
      steroid treatment and how to manage patients with established neuropathy who may
      require health services for many years. 

PMID- 24029147
TI  - Cytomegalovirus retinitis associated with HIV in resource-constrained settings:
      systematic screening and case detection.
AB  - Although cytomegalovirus (CMV) can cause a wide spectrum of multi-system
      disorders in HIV-infected patients, retinal disease is by far the most common
      clinical manifestation and may lead to blindness if untreated. We discuss the
      rationale for systematic case detection for CMV retinitis (CMVR) within the HIV
      affected population, focusing particularly on resource-limited settings. The gold
      standard for detection of CMVR is indirect ophthalmoscopy performed by a trained
      ophthalmologist. However this is generally not feasible in resource-constrained
      settings. Alternative methods include fundus photography or the use of laboratory
      techniques to detect CMV infection. Training and deployment of non-ophthalmic
      personnel to detect CMVR by ophthalmoscopy or with novel strategies may be a
      paradigm shift that needs to occur in order to provide effective systematic case
      detection for those at risk of CMVR in resource-constrained settings. Further
      research is needed to determine the diagnostic accuracy and operational
      feasibility of different strategies in resource-limited settings. 

PMID- 24029145
TI  - Pioglitazone reduces inflammation through inhibition of NF-kappaB in
      polymicrobial sepsis.
AB  - The insulin sensitizing thiazolidinedione drugs, rosiglitazone and pioglitazone
      are specific peroxisome proliferator-activated receptor-gamma agonists and reduce
      pro-inflammatory responses in patients with type 2 diabetes and coronary artery
      disease, and may be beneficial in sepsis. Sepsis was induced in 8-10-wk-old
      C57BL/6 mice by cecal ligation and puncture (CLP) with a 22 -g double puncture
      technique. Mice received an i.p. injection of vehicle (DMSO:PBS) or pioglitazone
      (20 mg/kg) at 1 h and 6 h after CLP, and were sacrificed at various time points.
      In sepsis, vehicle-treated mice had hypoglycemia, increased lung injury and
      increased lung neutrophil infiltration. Pro-inflammatory plasma cytokines were
      increased, but the plasma adipokine, adiponectin, was decreased in vehicle
      treated septic mice. This corresponded with inhibitor kappaB (IkappaBalpha)
      protein degradation and an increase in NF-kappaB activity in lung. Pioglitazone
      treatment improved plasma Glc and adiponectin levels, and decreased pro
      inflammatory cytokines. Lung IkappaBalpha protein expression increased and
      corresponded with a decrease in NF-kappaB activity in the lung from pioglitazone
      treated mice. Pioglitazone reduces the inflammatory response in polymicrobial
      sepsis in part through inhibition of NF-kappaB and may be a novel therapy in
      sepsis. 

PMID- 24029148
TI  - Household social determinants of ascariasis and trichuriasis in North Central
      Venezuela.
AB  - Ascariasis and trichuriasis are highly prevalent parasitoses in tropical
      countries caused by Ascaris lumbricoides and Trichuris trichiura, respectively.
      Their prevalence is associated with poor sanitation and hygiene, among other
      biological and social factors. In this study, the associations of household
      social determinants with these soil-transmitted helminthiases in North Central
      Venezuela was assessed in the context of a National Study on Human Growth and
      Development (SENACREDH). This was a probabilistic, stratified, cross-sectional
      survey with a sample of 3388 individuals that weighted represents 4 675 433
      inhabitants from the region. The prevalence of ascariasis and trichuriasis was
      3.73% and 1.13%, respectively. In the univariate and multivariate analyses, these
      prevalences were significantly higher in those living in vulnerable houses
      [adjusted OR (AOR) = 1.479, 95% CI 1.428-1.532; and AOR = 10.519, 95% CI 9.971
      11.097, respectively], houses located in rural areas (AOR = 2.067, 95% CI 2.035
      2.101; and AOR = 1.918, 95% CI 1.868-1.970, respectively) and houses with a soil
      floor (AOR = 5.027, 95% CI 4.895-5.162; and AOR = 5.190, 95% CI 4.944-5.448,
      respectively), among other factors. People living in rural households with
      inappropriate building materials, insufficient basic public services such as
      water and waste disposal, and surrounding disease-prone environments are at
      higher risk of acquiring A. lumbricoides and T. trichiura infections. 

PMID- 24029149
TI  - Effects of the SATZ teacher-led school HIV prevention programmes on adolescent
      sexual behaviour: cluster randomised controlled trials in three sub-Saharan
      African sites.
AB  - In this study, the effects on young adolescent sexual risk behaviour of teacher
      led school HIV prevention programmes were examined in two sites in South Africa
      (Cape Town and Mankweng) and one site in Tanzania (Dar es Salaam). In Cape Town,
      Dar es Salaam and Mankweng, 26, 24 and 30 schools, respectively, were randomly
      allocated to intervention or comparison groups. Primary outcomes were delayed
      sexual debut and condom use among adolescents aged 12-14 years (grade 8 in South
      Africa and grades 5 and 6 in Tanzania). In total, 5352, 4197 and 2590 students
      participated at baseline in 2004 in Cape Town, Dar es Salaam and Mankweng,
      respectively, and 73% (n = 3926), 88% (n = 3693) and 83% (n = 2142) were retained
      12-15 months later. At baseline, 13% (n = 224), 5% (n = 100) and 17% (n = 164)
      had had their sexual debut, and 44% (n = 122), 20% (n = 17) and 37% (n = 57) of
      these used a condom at last sex, respectively. In Dar es Salaam, students in the
      intervention were less likely to have their sexual debut during the study (OR
      0.65, 95% CI 0.48-0.87). In Cape Town and Mankweng, the intervention had no
      impact. The current interventions were effective at delaying sexual debut in Dar
      es Salaam but not in South Africa, where they need to be supplemented with
      programmes to change the environment in which adolescents make decisions about
      sexual behaviour. 

PMID- 24029150
TI  - Treatment costs of Mycobacterium ulcerans in the antibiotic era.
AB  - Mycobacterium ulcerans infection results in significant disfiguring morbidity,
      and treatment is expensive. To estimate the cost of treatment in the antibiotic
      era, a retrospective study of 71 patients diagnosed and treated for M. ulcerans
      in the Bellarine Peninsula (Victoria, Australia) between 1998 and 2006 was
      performed. Patients were categorised into minor single episode infection, major
      single episode infection and recurrent disease. Data were collected on each
      treatment cost component. To determine the change from costs in the pre
      antibiotic era, mean direct costs were compared with those from a study in a
      nearby region between 1991 and 1998. All costs were in Australian dollars in 2006
      2007 prices. The mean overall cost was $6181 per episode, with the highest cost
      components being hospitalisation (mean $3977; 63%) and surgeon fees ($949; 12%).
      Treatment costs per episode increased significantly from minor infection ($2235)
      to major infection ($6338) to recurrent disease ($13 372). Compared with the pre
      antibiotic era, costs have significantly decreased, with a 52% reduction in
      overall cost per episode, driven mainly by a reduction in hospitalisation costs.
      Therefore, earlier diagnosis and treatment of M. ulcerans, including the use of
      outpatient-based oral antibiotic regimens, has the potential to reduce the cost
      of treatment. 

PMID- 24029151
TI  - Full-term newborns with congenital microcephaly and macrocephaly in Southwest
      Nigeria.
AB  - This retrospective cohort study set out to determine perinatal and maternal
      factors associated with full-term (>=37 weeks) newborns with abnormal head sizes
      at birth in Lagos, Nigeria. Age and gender specific head circumference was
      determined with the current Child Growth Standards of the World Health
      Organization while maternal and infant factors independently associated with
      microcephaly (z-score < -2) and macrocephaly (z-score >2) were explored using
      multinomial logistic regression. Of the 3196 infants enrolled, 340 (10.6%) were
      microcephalic underpinned by suspected cytomegalovirus (CMV) infection while 74
      (2.3%) were macrocephalic. Compared with normocephalic newborns, microcephalic
      infants were more likely to be growth restricted in-utero (OR: 10.89; 95% CI:
      7.86-15.08); underweight (OR: 18.61; 95% CI: 13.28-26.07); stunted (OR: 15.45;
      95% CI: 11.70-20.40); and wasted (OR: 3.64; 95% CI: 2.52-5.27); as well as having
      an increased risk of unconjugated hyperbilirubinaemia but unlikely to be
      associated with prolonged/obstructed labour (OR: 0.49; 95% CI: 0.31-0.78). In
      contrast, macrocephalic infants were likely to be delivered by emergency
      caesarean section (OR: 2.32; 95% CI: 1.33-4.04) and at greater risk of neonatal
      sepsis (OR: 4.12; 95% CI: 1.68-10.40). Risk of sepsis in macrocephalic infants
      was more than two-fold compared with microcephalic infants but not statistically
      significant (p = 0.066). In conclusion, improved fetal growth monitoring, early
      nutritional intervention and management of perinatal infections are likely to
      curtail the burden of congenital microcephaly and macrocephaly in resource-poor
      settings. The underpinnings of unconjugated hyperbilirubinaemia in microcephalic
      infants in this CMV hyper-endemic population merit further investigation. 

PMID- 24029152
TI  - The Maoist insurgency (1996-2006) and child health indicators in Nepal.
AB  - The association of conflict and child health indicators in Nepal was examined for
      the period of the Communist Party of Nepal-Maoist (CPN-Maoist) insurgency (1996
      2006). National and subregional trends in neonatal protection against tetanus,
      measles and diphtheria-pertussis-tetanus (DPT) vaccine coverage, infant
      mortality, under-5 mortality, and proportion of underweight or stunted children
      were examined. During the period of the insurgency there were overall
      improvements in vaccination coverage; however, measles vaccine and DPT coverage
      remained static during several years of conflict. A decline in infant and under-5
      mortality rates occurred: however, there were smaller improvements in stunting
      and underweight children. Improvements in health indicators from the Mid-western
      Hill subregion of the country, an area that was consistently conflict-affected,
      were less than those achieved nationally or by the less-affected Eastern Hill
      subregion. In comparison with Bangladesh and India, improvements in Nepal were
      the same or better, except for stunting and underweight children. Health
      interventions that are more easily delivered, such as vaccination, showed
      improvements, although the changes were less in a region of high conflict.
      Improvements in child nutrition indicators that necessitate multiple, coordinated
      interventions and access to at-risk populations over time as well as ongoing food
      security were not as successful. Continued commitment to development of systems
      for delivery of child health is important to gain improvements across all
      childhood health indicators. 

PMID- 24029153
TI  - A qualitative study exploring delayed diagnosis and stigmatisation of
      tuberculosis amongst women in Uganda.
AB  - A qualitative study was undertaken to attempt to understand reasons for the
      delayed diagnosis of tuberculosis (TB) amongst Ugandan women and to describe the
      nature of TB stigma and its effects in Uganda. Twelve women were interviewed.
      Participants were selected on the basis that they had smear-positive TB and had
      delayed consulting healthcare services for >=30 days. Semi-structured interviews
      were conducted and analysed using thematic content analysis. The study showed
      that the main reason for delayed diagnosis amongst women interviewed was a lack
      of recognition of symptoms. This may be due to low levels of TB awareness in the
      community. The study also showed that TB is stigmatised in Uganda, mainly due to
      associations with HIV. Many participants believed that TB only exists with HIV
      and that TB causes HIV tests to appear negative even for HIV-infected people.
      Health education programmes would be helpful to improve the understanding of TB
      and to combat harmful beliefs about TB and HIV in the community. 

PMID- 24029154
TI  - Diagnosis and treatment of malaria by health care providers: findings from a post
      conflict district in Sri Lanka.
AB  - This study determines whether 72 health care providers in a previously conflict
      affected district in Sri Lanka adhere to the recommendations of the Anti Malaria
      Campaign with regard to diagnosis, prescribing antimalarials and reporting of a
      positive case. All patients suspected of clinically having malaria are being
      referred for laboratory confirmation, indicating that presumptive treatment is
      not practiced. The knowledge amongst health care providers regarding accurate
      management and reporting of a malaria positive case needs to be improved. 

PMID- 24029155
TI  - Comment on: Promotion of malaria home-based treatment in Africa: the dangers of
      creating a second health system.

PMID- 24029156
TI  - Planes formed with four intron-positions in tertiary structures of retinol
      binding protein and calpain domain VI.
AB  - Eukaryotic genes have intervening sequences, introns, in their coding regions.
      Since introns are spliced out from m-RNA before translation, they are considered
      to have no effect on the protein structure. Here, we report a novel relationship
      between introns and the tertiary structures of retinol binding protein and
      calpain domain VI. We identified "intron-positions" as amino acid residues on
      which or just after which introns are found in their corresponding nucleotide
      sequences, and then found that four intron-positions form a plane. We also found
      that the four intron-positions of retinol-binding protein encloses its ligand
      retinol. The tertiary structure of calpain domain VI changes after Ca(2+)
      binding, and the four intron-positions form a plane that includes its ligand
      calpastatin. To evaluate the statistical significance of the planarity, we
      calculated the mean distance of each intron-position from the plane defined by
      the other three intron-positions, and showed that it is significantly smaller
      than the one calculated for randomly generated locations based on exon size
      distribution. On the basis of this finding, we discuss the evolution of retinol
      binding protein and the origin of introns. 

PMID- 24029157
TI  - Can we heal Chagas infection?
AB  - We present a model for the parasite-antibody dynamical competition between
      Trypanosoma rangeli and its antibodies during the acute phase of an infection in
      a mammal host. The model reproduces experimental data from murine models found in
      the literature and allows us to demonstrate that a preinfection with T. rangeli
      induces a temporary protective effect against Chagas disease. As the mammal
      immune system is able to eliminate a single T. rangeli infection, the host high
      antibody levels, needed to resist the Chagas infection, are reduced with time,
      returning the system to the initial healthy state. Our results suggest that a
      preinfection with T. rangeli could be used to reduce the in-house vectorial
      parasitemia through repeated vaccination of domestic animals. 

PMID- 24029158
TI  - Kinetic characterization of on-chip DNA ligation on dendron-coated surfaces with
      nanoscaled lateral spacings.
AB  - We analyzed the enzymatic profiles of on-chip DNA ligation as we controlled the
      lateral spacing of surface-immobilized DNA substrates using dendron molecules
      with different sizes at the nanoscale. Enzymatic on-chip DNA ligation was
      performed on the dendron-coated surface within 20 min with no need for post
      ligation gel electrophoresis. The enzymatic DNA repair was assessed by the
      fluorescence intensity at the repaired DNA duplex after thermally dissociating
      the unligated Cy3-labeled DNA from the DNA duplex, in which the Cy3-labeled DNA
      was hybridized prior to the on-chip DNA ligation. The rate of the nick-sealing
      reaction on the 27-acid dendron surface was 3-fold higher than that on the 9-acid
      dendron surface, suggesting that the wider lateral spacing determined by the
      larger dendron molecule could facilitate the access of DNA ligase to the nick
      site. The performance of on-chip DNA ligation was dropped to 10% and 3% when the
      nick was replaced by one- and two-nucleotide-long gaps, respectively. The 5'
      terminal phosphorylation of DNA strands by polynucleotide kinase and the on-chip
      DNA cleavage by endonucleases were also quantitatively monitored throughout the
      on-chip DNA ligation on the dendron-coated surface. A better understanding of the
      enzymatic kinetics of on-chip DNA ligation will contribute to a more reliable
      performance of various on-chip DNA ligation-based assays.

PMID- 24029159
TI  - Seroprevalence of Sindbis virus and associated risk factors in northern Sweden.
AB  - Mosquito-borne Sindbis virus (SINV) cause disease characterized by rash, fever
      and arthritis which often leads to long-lasting arthralgia. To determine the
      seroprevalence of SINV and associated risk factors in northern Sweden, a randomly
      selected population aged between 25 and 74 years were invited to join the MONICA
      study. Serum from 1611 samples were analysed for specific IgG antibodies.
      Overall, 2.9% had IgG against SINV. More men (3.7%) than women (2.0%) were SINV
      seropositive (P = 0.047) and it was more common in subjects with a lower
      educational level (P = 0.013) and living in small, rural communities (P < 0.001).
      Seropositivity was associated with higher waist circumference (P = 0.1), elevated
      diastolic blood pressure (P = 0.037), and history of a previous stroke (P =
      0.011). In a multiple logistic regression analysis, adjusting for known risk
      factors for stroke, seropositivity for SINV was an independent predictor of
      having had a stroke (odds ratio 4.3, 95% confidence interval 1.4-13.0, P =
      0.011).

PMID- 24029160
TI  - Portosystemic pressure reduction achieved with TIPPS and impact of portosystemic
      collaterals for the prediction of the portosystemic-pressure gradient in
      cirrhotic patients.
AB  - PURPOSE: The portosystemic pressure gradient is an important factor defining
      prognosis in hepatic disease. However, noninvasive prediction of the gradient and
      the possible reduction by establishment of a TIPSS is challenging. A cohort of
      patients receiving TIPSS was evaluated with regard to imaging features of
      collaterals in cross-sectional imaging and the achievable reduction of the
      pressure gradient by establishment of a TIPSS. METHODS: In this study 70
      consecutive patients with cirrhotic liver disease were retrospectively evaluated.
      Patients received either CT or MR imaging before invasive pressure measurement
      during TIPSS procedure. Images were evaluated with regard to esophageal and
      fundus varices, splenorenal collaterals, short gastric vein and paraumbilical
      vein. Results were correlated with Child stage, portosystemic pressure gradient
      and post-TIPSS reduction of the pressure gradient. RESULTS: In 55 of the 70
      patients TIPSS reduced the pressure gradient to less than 12 mmHg. The pre
      interventional pressure and the pressure reduction were not significantly
      different between Child stages. Imaging features of varices and portosystemic
      collaterals did not show significant differences. The only parameter with a
      significant predictive value for the reduction of the pressure gradient was the
      pre-TIPSS pressure gradient (r = 0.8, p<0.001). CONCLUSIONS: TIPSS allows a
      reliable reduction of the pressure gradient even at high pre-interventional
      pressure levels and a high collateral presence. In patients receiving TIPSS the
      presence and the characteristics of the collateral vessels seem to be too
      variable to draw reliable conclusions concerning the portosystemic pressure
      gradient.

PMID- 24029161
TI  - Perfusion characteristics of parotid gland tumors evaluated by contrast-enhanced
      ultrasound.
AB  - PURPOSE: Contrast enhanced ultrasound (CE-US) is a promising imaging modality for
      non-invasive analysis of parotid gland lesions because their vascularisation
      differs from normal gland tissue. This clinical study should further investigate
      CE-US as a diagnostic tool for parotid gland tumors. MATERIALS AND METHODS: 39
      patients underwent CE-US measurements after intravenous application of a contrast
      agent (SonoVue, Bracco, Italy) before surgical tumor resection. Time-intensity
      curves gradients were calculated and parameters of intratumoral microcirculation
      were analysed. The vascularisation parameters were compared among the different
      tumor entities as defined per definitive histological diagnosis. RESULTS:
      Histological analyses revealed 17 pleomorphic adenoma, 15 cystadenolymphoma and 7
      malignoma. A significant difference of area below intensity time curve (AUC) and
      mean transit time (MTT) was measured in the malignant lesions compared to benign
      tumors (p<0.05). A significant difference of AUC and maximum of signal increase
      (DeltaSImax) for pleomorphic adenoma versus cystadenolymphoma was found (p<0.05).
      CONCLUSION: CE-US seems to be a quantitative and independent method for the
      assessment of malign and benign parotid gland tumors. Further studies and
      clinical experience will have to validate this method as a reliable diagnostic
      tool that facilitates preoperative planning.

PMID- 24029163
TI  - Resting heart rate and the association of physical fitness with carotid artery
      stiffness.
AB  - BACKGROUND: Physical fitness is known to influence arterial stiffness. Resting
      heart rate is reduced by exercise and positively associated with arterial
      stiffness. This study aimed to investigate the role of resting heart rate in the
      relationship of physical fitness with arterial stiffness. METHODS: Subjects were
      2,328 young adults from the Childhood Determinants of Adult Health study.
      Cardiorespiratory fitness was estimated as physical work capacity at a heart rate
      of 170 bpm. Muscular strength was estimated by hand-grip (both sides), shoulder
      (pull and push), and leg strength. Arterial stiffness was measured using carotid
      ultrasound. RESULTS: Arterial stiffness was negatively associated with
      cardiorespiratory fitness (men P < 0.001; women P = 0.002), and positively
      associated with muscular strength in women (P = 0.002) but not in men. Resting
      heart rate was positively associated with arterial stiffness (P < 0.001 both men
      and women). Adjustment for resting heart rate reduced the inverse association of
      arterial stiffness with cardiorespiratory fitness by 93.7% (men) and 67.6%
      (women) but substantially increased the positive association of arterial
      stiffness with muscular strength among women and revealed a positive association
      of arterial stiffness with muscular strength among men. These findings were
      independent of body size, blood pressure, biochemical markers, socioeconomic
      status, smoking, and alcohol consumption. CONCLUSIONS: Our findings attribute a
      key intermediary role for resting heart rate in the relationship between fitness
      and arterial stiffness, whereby higher cardiorespiratory fitness may reduce
      arterial stiffness mainly through resting heart rate, and higher muscular
      strength might have deleterious effects on arterial stiffness that are partially
      offset by lower resting heart rate.

PMID- 24029162
TI  - Body mass index modulates blood pressure heritability: the Family Blood Pressure
      Program.
AB  - BACKGROUND: Candidate gene and twin studies suggest that interactions between
      body mass index (BMI) and genes contribute to the variability of blood pressure
      (BP). To determine whether there is evidence for gene-BMI interactions, we
      investigated the modulation of BP heritability by BMI using 4,153 blacks, 1,538
      Asians, 4,013 whites, and 2,199 Hispanic Americans from the Family Blood Pressure
      Program. METHODS: To capture the BP heritability dependence on BMI, we employed a
      generalized variance components model incorporating linear and Gaussian
      interactions between BMI and the genetic component. Within each race and network
      subgroup, we used the Akaike information criterion and likelihood ratio test to
      select the appropriate interaction function for each BP trait (systolic BP (SBP),
      diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)) and
      determine interaction significance, respectively. RESULTS: BP heritabilities were
      significantly modified by BMI in the GenNet and SAPPHIRe Networks, which
      contained the youngest and least-obese participants, respectively. GenNet Whites
      had unimodal SBP, MAP, and PP heritabilities that peaked between BMI values of 33
      and 37kg/m(2). The SBP and MAP heritabilities in GenNet Hispanic Americans, as
      well as the PP heritability in GenNet blacks, were increasing functions of BMI.
      The DBP and SBP heritabilities in the SAPPHIRe Chinese and Japanese,
      respectively, were decreasing functions of BMI. CONCLUSIONS: BP heritability
      differed by BMI in the youngest and least-obese networks, although the shape of
      this dependence differed by race. Use of nonlinear gene-BMI interactions may
      enhance BP gene discovery efforts in individuals of European ancestry.

PMID- 24029164
TI  - Is pulse pressure an independent risk factor for incident acute coronary heart
      disease events? The REGARDS study.
AB  - BACKGROUND: Increased attention has been given to pulse pressure (PP) as a
      potential independent risk factor for cardiovascular disease (CVD). We examined
      the relationship between the three indices of blood pressure consisting of
      systolic blood pressure (SBP), diastolic blood pressure (DBP), and PP (= SBP -
      DBP), respectively, and incident acute coronary heart disease (CHD). METHODS:
      Participants in the REasons for Geographic And Racial Differences in Stroke
      (REGARDS) Study, a national cohort study of 30,239 black and white participants >
      45 years of age, were enrolled between 2003 and 2007. The participants' SBP, DBP,
      and PP values were separated into the four groups of < 45mm Hg, 45-54.9mm Hg, 55
      64.9mm Hg, and >= 65mm Hg, and were analyzed on a groupwise basis. Reported CHD
      events were confirmed by expert adjudication. Cox proportional hazards models
      were used to examine the association of incident CHD (first acute CHD event) for
      the four groups of BP measurements with multivariate-adjusted sociodemographic
      and clinical risk factors. RESULTS: Analyses were done for 22,909 men and women
      (40.4% black, 44.6% male) >= 45 years of age (mean age = 64.7+/-9.4 years)
      without prevalent CHD at baseline. Associations were found for 681 CHD events,
      over a mean 3.4 years of follow-up (maximum 6 years), with each unadjusted PP
      group (hazard ratio [HR] with 95% confidence limits for PP of 45-54.9mm Hg, 55
      64.9mm Hg, and >= 65mm Hg, respectively, of 3.82, 3.08, and 4.73 as compared with
      PP < 45mm Hg; P < 0.0001 for linear trend), and this persisted after full
      adjustment, including that for SBP (1.50, 1.08, 2.09; P trend < 0.01). Subgroup
      analyses showed no statistically significant differences across age, race, or
      region of the country, but did suggest the possibility that men were more
      sensitive to PP than were women. CONCLUSIONS: Pulse pressure is positively and
      independently (particularly so with regard to independence from SBP) associated
      with incident CHD, and there were no significant racial or regional differences
      in this association.

PMID- 24029165
TI  - Electronic cigarettes for smoking cessation: a randomised controlled trial.
AB  - BACKGROUND: Electronic cigarettes (e-cigarettes) can deliver nicotine and
      mitigate tobacco withdrawal and are used by many smokers to assist quit attempts.
      We investigated whether e-cigarettes are more effective than nicotine patches at
      helping smokers to quit. METHODS: We did this pragmatic randomised-controlled
      superiority trial in Auckland, New Zealand, between Sept 6, 2011, and July 5,
      2013. Adult (>=18 years) smokers wanting to quit were randomised (with
      computerised block randomisation, block size nine, stratified by ethnicity
      [Maori; Pacific; or non-Maori, non-Pacific], sex [men or women], and level of
      nicotine dependence [>5 or <=5 Fagerstrom test for nicotine dependence]) in a
      4:4:1 ratio to 16 mg nicotine e-cigarettes, nicotine patches (21 mg patch, one
      daily), or placebo e-cigarettes (no nicotine), from 1 week before until 12 weeks
      after quit day, with low intensity behavioural support via voluntary telephone
      counselling. The primary outcome was biochemically verified continuous abstinence
      at 6 months (exhaled breath carbon monoxide measurement <10 ppm). Primary
      analysis was by intention to treat. This trial is registered with the Australian
      New Zealand Clinical Trials Registry, number ACTRN12610000866000. FINDINGS: 657
      people were randomised (289 to nicotine e-cigarettes, 295 to patches, and 73 to
      placebo e-cigarettes) and were included in the intention-to-treat analysis. At 6
      months, verified abstinence was 7.3% (21 of 289) with nicotine e-cigarettes, 5.8%
      (17 of 295) with patches, and 4.1% (three of 73) with placebo e-cigarettes (risk
      difference for nicotine e-cigarette vs patches 1.51 [95% CI -2.49 to 5.51]; for
      nicotine e-cigarettes vs placebo e-cigarettes 3.16 [95% CI -2.29 to 8.61]).
      Achievement of abstinence was substantially lower than we anticipated for the
      power calculation, thus we had insufficient statistical power to conclude
      superiority of nicotine e-cigarettes to patches or to placebo e-cigarettes. We
      identified no significant differences in adverse events, with 137 events in the
      nicotine e-cigarettes group, 119 events in the patches group, and 36 events in
      the placebo e-cigarettes group. We noted no evidence of an association between
      adverse events and study product. INTERPRETATION: E-cigarettes, with or without
      nicotine, were modestly effective at helping smokers to quit, with similar
      achievement of abstinence as with nicotine patches, and few adverse events.
      Uncertainty exists about the place of e-cigarettes in tobacco control, and more
      research is urgently needed to clearly establish their overall benefits and harms
      at both individual and population levels. FUNDING: Health Research Council of New
      Zealand.

PMID- 24029166
TI  - Effect of the first federally funded US antismoking national media campaign.
AB  - BACKGROUND: Every year, smoking kills more than 5 million people globally,
      including 440,000 people in the USA, where the long-term decline in smoking
      prevalence has slowed. The US Centers for Disease Control and Prevention (CDC)
      delivered a national, 3-month antismoking campaign called Tips From Former
      Smokers (Tips) that started in March, 2012, in which hard-hitting, emotionally
      evocative television advertising was featured, depicting smoking-related
      suffering in real people. We aimed to assess the effects of the Tips campaign.
      METHODS: We undertook baseline and follow-up surveys of nationally representative
      cohorts of adult smokers and non-smokers. The national effect of the Tips
      campaign was estimated by applying rates of change in the cohort before and after
      the campaign to US census data. FINDINGS: 3051 smokers and 2220 non-smokers
      completed baseline and follow-up assessments. 2395 (78%) smokers and 1632 (74%)
      non-smokers recalled seeing at least one Tips advertisement on television during
      the 3-month campaign. Quit attempts among smokers rose from 31.1% (95% CI 30.3
      31.9) at baseline to 34.8% (34.0-35.7) at follow-up, a 12% relative increase. The
      prevalence of abstinence at follow-up among smokers who made a quit attempt was
      13.4% (95% CI 9.7-17.2). Nationally, an estimated 1.64 million additional smokers
      made a quit attempt, and 220,000 (95% CI 159,000-282,000) remained abstinent at
      follow-up. Recommendations by non-smokers to quit grew from 2.6% at baseline to
      5.1% at follow-up, and the prevalence of people talking with friends and family
      about the dangers of smoking rose from 31.9% (95% CI 31.3-32.5) to 35.2% (34.6
      35.9), resulting in an estimated 4.7 million additional non-smokers recommending
      cessation services and more than 6 million talking about the dangers of smoking.
      INTERPRETATION: The high-exposure Tips media campaign was effective at increasing
      population-level quit attempts. The growth in smokers who quit and became
      sustained quitters could have added from a third to almost half a million quality
      adjusted life-years to the US population. Expanded implementation of similar
      campaigns globally could accelerate progress on the WHO Framework Convention on
      Tobacco Control and reduce smoking prevalence globally. FUNDING: CDC, US
      Department of Health and Human Services.

PMID- 24029167
TI  - Effects of a short-term mass-media campaign against smoking.

PMID- 24029168
TI  - Electronic cigarettes for smoking cessation.

PMID- 24029169
TI  - Haemoproteus syrnii in Strix aluco from France: morphology, stages of sporogony
      in a hippoboscid fly, molecular characterization and discussion on the
      identification of Haemoproteus species.
AB  - In France, Haemoproteus syrnii is frequently found in the Tawny Owl, Strix aluco.
      Additional and complementary features of this species, and in particular the
      characteristics of volutin, are presented. The authors consider the volutin
      granules as constant in a given species, and discuss their taxonomic value. These
      cytoplasmic inclusions appear early during the first stages of development of the
      gametocytes as an initial granule which multiplies as the parasite develops. They
      were reported in some species of Haemoproteus but are seldom considered as a
      specific character and described with precision. Sporogony from ookinete to
      apparently mature sporozoites appears to take place in a pupiparous hippoboscid
      (Ornithomyia sp.). One specimen was crushed between two slides and stained with
      Giemsa. Gametocytes of H. syrnii, many ookinetes, an immature oocyst and mature
      sporozoites were observed spread all over the smear. This would allow classifying
      this species in the Haemoproteus subgenus. We provide associated molecular data
      derived from the cyt b and cox 1 gene from this parasite. We discuss the problems
      of multiple infections and the difficulties in identifying Haemoproteus species
      and in deriving conclusions from sequences deposited in databases. 

PMID- 24029170
TI  - Chitosan/o-carboxymethyl chitosan nanoparticles for efficient and safe oral
      anticancer drug delivery: in vitro and in vivo evaluation.
AB  - The present study investigated the ability of a polyelectrolyte complex (CS/CMCS
      NPs), composed of chitosan (CS) and o-carboxymeymethy chitosan (CMCS) as a pH
      responsive carrier for oral delivery of doxorubicin hydrochloride (DOX). The
      obtained CS/CMCS-NPs were characterized for various parameters including
      morphology, particle size, zeta potential, entrapment efficiency and stability
      under the simulated GI tract conditions. The pH responsive stability of the DOX
      loaded CS/CMCS nanoparticles (DOX:CS/CMCS-NPs) determined the drug release rate,
      which was lower in acidic pH than the neutral. Ex vivo intestinal adhesion and
      permeation indicated DOX:CS/CMCS-NGs were able to enhance absorption of DOX
      throughout the entire small intestine, especially in jejunum and ileum. Oral
      administration of DOX:CS/CMCS-NPs was effective to deliver DOX into blood, giving
      an absolute bioavailability of 42%. The tissue distribution and toxicity of
      DOX:CS/CMCS-NPs in rats showed low level of DOX in heart and kidney, and
      obviously decreased cardiac and renal toxicities. These results indicated CS/CMCS
      NPs were highly efficient and safe as an oral delivery system for DOX. 

PMID- 24029171
TI  - Transungual delivery of ketoconazole using novel lacquer formulation.
AB  - Onychomycosis, a common fungal infection of the nail, can have a substantial
      impact on quality of life. The success of topical therapy for onychomycosis
      depends on effective penetration, which can be enhanced using an appropriate
      delivery method. This study evaluated the effectiveness of a novel topical
      lacquer on enhancing [(14)C]-ketoconazole penetration by comparing nail
      absorption, nail distribution, and nail penetration of [(14)C]-ketoconazole
      dissolved in the novel lacquer versus a commercial ketoconazole cream. Using the
      in vitro finite dose model, the formulations were applied daily to human nail
      plates for 7 days. Drug absorption was measured by monitoring rate of appearance
      in each nail layer and the supporting bed. After the multiple day treatment,
      cumulative concentrations of ketoconazole formulated in novel lacquer in the deep
      nail layer and the nail bed were significantly greater than cumulative
      concentrations of commercial ketoconazole (p<0.05), as well as several orders of
      magnitude greater than the minimal inhibitory concentration (MIC) deemed
      necessary to inhibit the growth of causative dermatophytic and yeast species.
      These results suggest that this novel ketoconazole lacquer has the potential to
      be an effective topical treatment for onychomycosis. 

PMID- 24029172
TI  - [Operational tolerance in liver transplantation is more frequent than expected
      and increases with time after the intervention].

PMID- 24029173
TI  - [Synchronic MALT lymphoma and carcinoid tumor of the ileum].

PMID- 24029174
TI  - [Infliximab in the treatment of refractory gastroduodenal Crohn's disease].

PMID- 24029176
TI  - Practical Aspects of Shortening Acquisition Time in Brain MR Susceptibility
      Weighted Imaging.
AB  - Magnetic resonance susceptibility-weighted imaging (SWI), a novel 3D gradient
      echo MRI sequence exploiting phase and magnitude data for post-processing, is
      able to detect blood, iron, calcification and deoxygenated hemoglobin content for
      brain. SWI has been widely used to evaluate cerebral vascular disorders, trauma,
      multiple sclerosis, and tumors. We have also used SWI to evaluate acute stroke
      patients to identify thrombosis and possible penumbra. The acquisition was too
      long for examining acute stroke patients due to motion from agitation and mental
      changes. We have altered the parameters of phase resolution, voxel size, matrix
      size and partial Fourier to shorten the acquisition time to improve the
      diagnostic quality of SWI for acute stroke patients. The result was to reduce the
      acquisition time from 3:46 min to 2:14 min thereby providing a helpful tool in
      screening stroke patients. 

PMID- 24029175
TI  - MRI findings in low grade tumours associated with focal cortical dysplasia.
AB  - Magnetic resonance imaging (MRI) is mandatory to identify the epileptogenic zone
      in refractory temporal lobe epilepsy (TLE). The correct identification of lesions
      is essential to obtain good post-surgery seizure control. Low grade tumours (LGT)
      and focal cortical dysplasia (FCD) are common findings in symptomatic TLE, and
      frequently coexist. The aim of this study was to identify the MRI characteristics
      in the diagnosis of FCD associated with LGT. We analyzed 24 subjects with TLE who
      underwent tailored surgery. They all had LGTs. Two expert neuroradiologists
      analyzed the imaging data and compared them with histological results,
      hypothesizing the causes of diagnostic errors in the identification of FCD. We
      selected three exemplary cases to report the most important causes of errors. In
      the diagnosis of FCD we reported false positives and false negatives due to
      different causes. An incomplete MRI protocol, the large dimensions of the tumour,
      infiltration and related oedema were the most important factors limiting MRI
      accuracy. MRI can be limited by an incomplete protocol. In addition, the presence
      of an LGT may limit the neuroradiological diagnosis of FCD in the temporal lobe.
      Advanced MRI techniques could help reveal subtle lesions that eluded a previous
      imaging inspection. 

PMID- 24029177
TI  - Diffusion-Weighted Imaging of the Early Phase of Wallerian Degeneration. A Report
      of two Pediatric Cases and Literature Review.
AB  - Wallerian degeneration (WD) affects axons and their myelin sheaths distally from
      the site of injury of the axon and/or body of the neuron. There is limited
      knowledge about brain injuries in newborns, mostly because non-invasive imaging
      sensitive enough to detect subtle changes was not available. Diffusion-weighted
      magnetic resonance (MR) imaging (DWI) is sensitive in the detection of early
      injury to the corticospinal tracts (CST) before the occurrence of WD in distal
      segments. We describe the cases of 14- and seven-day-old newborns in whom MR
      imaging revealed vascular injury in the territory supplied by the middle cerebral
      artery, and early development of WD. We performed DWI and faced an unexpected
      finding because DWI hyperintensities were at the same time hyperintense on T2
      weighted images. Hyperintense structures on DWI are supposed to reflect pre
      Wallerian injured tissue, which should not be visible on standard MR sequences,
      while their T2- signal indicated the third, late subacute phase of WD. It seems
      that time-related stages of WD observed in adults do not necessarily apply to the
      immature brain of newborns/infants as reflected by differences in signal
      intensity in various MR sequences. DWI hyperintensity in CST below infarct should
      not be mistaken for new ischemic foci. 

PMID- 24029178
TI  - Guillain-barre syndrome associated with acute onset bilateral facial nerve
      palsies. A case report and literature review.
AB  - Guillain-Barre syndrome is a post infectious, immune-mediated disease with
      cranial nerve involvement observed in 45-75% of patients. Bilateral facial nerve
      palsy is rather uncommon and occurs in 0.3% to 2% of all facial palsies. We
      describe a rare case of a 29-year-old man with bilateral facial palsy caused by a
      Guillain-Barre syndrome with an unusual onset and progression of neurological
      symptoms. Neuroradiological findings in our patient are described and compared
      with data from literature on bilateral facial palsies to make differential
      diagnosis easier for neuroradiologists. 

PMID- 24029179
TI  - Cortical Laminar Necrosis and CT Negative Hemorrhage in Posterior Reversible
      Encephalopathy Syndrome. A Case Report.
AB  - Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiologic
      condition that typically demonstrates symmetric occipitoparietal vasogenic edema
      on CT and MR imaging. The vasogenic edema typically resolves over a period of
      days to weeks if the underlying hemodynamic abnormality is promptly corrected.
      Less commonly, PRES may be complicated by hemorrhage or cytotoxic edema that
      restricts diffusion and usually involves the cerebral cortex. Cortical laminar
      necrosis (CLN) is a sequela of cerebral energy depletion, resulting in selective
      necrosis of the most metabolically active cortical layers. Cortical hemorrhage is
      an atypical feature of CLN. We present a unique PRES case with imaging features
      of both CLN and CT negative hemorrhage. CLN with CT negative hemorrhage in the
      setting of PRES has not been previously reported to the best of our knowledge. 

PMID- 24029180
TI  - Challenging pyogenic cerebral abscess complicated by subdural empyema. A case
      report.
AB  - Brain abscesses develop in response to a parenchymal infection with pyogenic
      bacteria, beginning as a localized area of cerebritis and evolving into a
      suppurative lesion surrounded by a well-vascularized fibrotic capsule. The
      leading etiologic agents of brain abscess are the streptococcal strains and S.
      aureus. Abscesses may also be secondary to fungal or parasitic organisms. Brain
      abscess represents a significant medical problem, accounting for one in every
      10,000 hospital admissions in the United States, and remains a serious situation
      despite recent advances made in detection and therapy. These lesions often
      produce complex clinical and radiologic findings and require prompt recognition
      and treatment to avoid a fatal neurologic outcome. Subdural empyema represents an
      important type of intracranial suppurative infectious-inflammatory disorder.
      Clinically, these patients initially have signs and symptoms of meningitis, but
      this course might be complicated later by the development of seizures and focal
      neurologic signs. 

PMID- 24029181
TI  - A rare case of intraosseous lipoma involving the sphenoclival region.
AB  - We describe the case of a 23-year-old man whose CT scan revealed a hypodense
      lesion reshaping the superior and middle third of the clivus and partially
      invading the sphenoidal sinus. MRI showed an irregular-shaped lesion occupying
      the body of the sphenoid bone, involving the superior and middle third of the
      clivus and sprouting into the sphenoid sinus. The lesion was hyperintense on T1-
      and T2-weighted sequences with a thin peripheral rim of hypointensity, without
      enhancement after i.v. gadolinium injection. The pathology report confirmed an
      intraosseus lipoma. Intraosseous lipomas involving the spheno-clival region are
      extremely rare. CT and MRI scan interpretation can be troublesome but this rare
      pathology has to be considered in the differential diagnosis. 

PMID- 24029182
TI  - Pediatric inflammatory diseases. Part I: multiple sclerosis.
AB  - Multiple sclerosis (MS) is an inflammatory CNS disease characterized by
      multifocal areas of demyelination; usually it arises in young adults, but can
      also occur in children (under the age of 10) and adolescents (under the age of
      18). As in adult, pediatric MS (PMS) diagnosis is based on the demonstration of
      multiple demyelination episodes separated in time and spaces. Diagnostic criteria
      realized for childhood are similar to those employed for adults. Although
      clinical and imaging features of PMS can be similar to those of adults, the
      disease is often characterized by a more aggressive course and atypical imaging
      findings, with giant and pseudotumoral plaques. Differential diagnosis between
      PMS and ADEM could be difficult: clinical findings and MRI are necessary;
      sometimes MRI follow-up is required for definitive diagnosis. 

PMID- 24029183
TI  - Endovascular treatment of a giant dissecting aneurysm of the posterior cerebral
      artery. A case report and literature review.
AB  - We describe the case of a 60-year-old man who presented with a giant dissecting
      aneurysm of the left P2 segment. Intracranial dissecting aneurysms often occur in
      the vertebrobasilar system, but rarely involve the posterior cerebral artery
      (PCA). PCA aneurysms tend to have some peculiar features and therefore may be
      considered a separate entity, even from the vertebrobasilar aneurysms. The
      patient was treated by endovascular occlusion of both parent vessel and the
      aneurysm, and he tolerated the procedure well with a complete resolution of
      clinical deficit, following volume reduction of the aneurysm. This paper presents
      additional evidence to literature reports suggesting that endovascular parent
      artery occlusion with coils is an effective and well-tolerated treatment for
      distal PCA aneurysms. Our review contributes to collect data regarding the
      incidence of recurrence as a measure of long-term efficacy of this therapeutic
      approach. 

PMID- 24029184
TI  - Pediatric Inflammatory Diseases. Part II: Acute Post-Infectious Immune Disorders.
AB  - Acute post-infectious immune disorders include Acute Disseminated
      Encephalomyelitis (ADEM) and its variants such as Acute Hemorrhagic
      Encephalomyelitis (AHEM), acute necrotizing hemorrhagic leukoencephalitis (ANHLE)
      of Weston Hurst, multiphasic and recurrent ADEM. Acute Necrotizing Encephalopathy
      of Childhood (ANE or ANEC) represents a dramatic event, consequent to viral
      infections, especially Influenza-A, and is now considered different from ADEM.
      ADEM and variants are classically described as uniphasic syndrome occurring in
      association with an immunization or vaccination (postvaccine encephalomyelitis)
      or systemic viral infection (parainfectious encephalomyelitis). However,
      multiphasic forms are not rare. Pathologically, there is perivascular
      inflammation, edema, and demyelination within the CNS. Clinical features are
      focal or multifocal neurologic disorder following exposure to virus or receipt of
      vaccine. The onset of the CNS disorder is usually rapid and include
      encephalopathy ranging from lethargy to coma, seizures, and focal and multifocal
      signs reflecting cerebral and spinal cord involvement. The mortality rate is
      estimated at 10 to 30 percent, with complete recovery rates of 50 percent cited.
      Poor prognosis is correlated with severity and abruptness of onset of the
      clinical syndrome. Multifocal CNS lesions are generally evident on MRI that can
      be similar from those observed in MS. 

PMID- 24029185
TI  - Pediatric Inflammatory Diseases. Part III: Small Vessels Vasculitis.
AB  - Central nervous system (CNS) vasculitis can affect both adults and children, but
      some of these occur almost exclusively in childhood. In children may develop as a
      primary condition or secondary to an underlying systemic disease. Cerebral
      vasculitis can be classified on the basis of the diameter of the involved
      vessels, although there is no univocal consensus. The diagnosis of CNS vasculitis
      is particularly difficult because the available investigative modalities have
      limited sensitivities and specificities. The most helpful diagnostic tests
      include cerebrospinal fluid analysis, MRI (MR angiography/venography (MRA/MRV) of
      the brain, and angiography. However, brain biopsy may be required to diagnose
      small vessel vasculitis in order to make differential diagnosis with a wide range
      of conditions, such as degenerative vasculopathies, embolic diseases, or
      coagulation disorders. This paper discusses on current understanding of most
      frequent primary and secondary central nervous system vasculitis in children in
      which are involved small vessel. 

PMID- 24029186
TI  - Pediatric Inflammatory Diseases. Part IV: Miscellaneous, Reye, PRES, Sarcoidosis.
AB  - Some rare neurological diseases affecting children have no well defined etiology
      and pathogenetic mechanisms. In this article diseases like Reye syndrome, Behcet
      disease, pediatric neurosarcoidosis, Posterior Reversible Encephalopathy Syndrome
      are described. Some of the main neuroradiological differential aspects are also
      critically considered. Reye syndrome is characterized by symmetric thalamic,
      white matter and basal ganglia lesions, in children with recent history of
      salycilates or immunosuppressive drugs intake. The most typical MRI feature of
      neurosarcoidosis is basilar meningeal thickening and enhancement with
      intraparenchymal enhancing nodules and white matter focal abnormalities. The
      classical distribution of lesions helps differential diagnosis with infectious
      meningoencephalitis. Differential diagnosis with relapsing-remitting multiple
      sclerosis his helped by the evidence of meningeal abnormalities. Neuro-Behcet is
      characterized by mesodiencephalic lesions in children with encephalopathy and
      coexistence of oral and genital ulcers and ocular abnormalities. PRES can be
      differentiated from vasculitis for the typical posterior white matter involvement
      and the different clinical features. 

PMID- 24029187
TI  - Basilar artery hypoplasia.
AB  - A rare case of segmental hypoplasia of the basilar artery is described in a 49
      year-old man with transient vertebrobasilar ischemia, explored by magnetic
      resonance imaging (MRI) and digital angiography (DA). The embryology, clinical
      relevance and magnetic resonance findings of this arterial anomaly are discussed,
      with a review of six previously reported cases. Segmental aplasia was suggested
      in our case by magnetic resonance, and subsequently confirmed not only by time-of
      flight magnetic resonance, but also by DA. Only ultrathin-slice T2-weighted
      images revealed the real finding of basilar artery hypoplasia. This sequence, not
      employed in previously reported cases, is mandatory to allow a clear differential
      diagnosis between basilar artery aplasia and hypoplasia. 

PMID- 24029188
TI  - Large capillary telangiectasia and developmental venous anomaly of the Basal
      Ganglia: an unusual finding.
AB  - Brain capillary telangiectasias are small, benign, asymptomatic, angiographically
      occult lesions that are incidentally discovered either at autopsy or on MR
      imaging in most cases. They are commonly located in the pons and can be
      associated with other vascular malformations. We describe a case of an unusually
      large capillary telangiectasia associated with a developmental venous anomaly
      involving the basal ganglia in a young woman, in which MR serial imaging
      suggested the diagnosis and avoided an unnecessary stereotaxic biopsy. 

PMID- 24029189
TI  - Progressive AVM Thrombosis after Onyx Embolization with Angiographic Cure.
AB  - Intracranial arteriovenous malformations (AVMs) have a cumulative risk of
      hemorrhage and refractory seizures. Pre-surgical Onyx embolization of cerebral
      AVMs improves clinical outcome. A 45-year-old man with a history of seizures was
      diagnosed with a Spetzler-Martin grade 4 AVM in the right occipital lobe. As per
      initial assessment, three to four sessions were required for adequate
      devascularization of the AVM before offering either surgery or gamma knife
      treatment. We achieved 10% and 70% devascularization in the first and second
      stage Onyx18 embolization respectively. Subsequent bilateral internal carotid,
      external carotid, vertebral and right posterior cerebral artery superselective
      angiography performed six weeks after the second stage of embolization
      demonstrated unexpected complete angiographic cure of the AVM. 

PMID- 24029190
TI  - Magnetic resonance imaging in neuronal ceroid lipofuscinosis and its subtypes.
AB  - Studies on magnetic resonance imaging (MRI) observations in neuronal ceroid
      lipofuscinosis (NCL) are few and far between. We evaluated the MRI
      characteristics of patients with NCL and its subtypes. Forty-three out of 68
      patients with ultrastructurally confirmed NCL (M:F=46:22; age at evaluation:
      6.3+/-5.2 years) underwent brain MRI evaluation (1998-2010). The demography,
      phenotype and subtypes of NCL (n=43) [infantile (I-NCL): 5; late infantile (LI
      NCL): 26; Juvenile (J-NCL): 11; adult (A-NCL): 1] were recorded. MRI (brain) was
      carried out using standard sequences in all. Brain atrophy and signal alterations
      were assessed visually. Brain MRI was abnormal in all 43 patients - diffuse
      cerebral atrophy (100%), cerebellar atrophy (40%), cerebral leucoencephalopathy
      (65%) and thalamic T2W-hypointensity (33%). Diffuse cerebral atrophy was noted
      in: I-NCL (100%), LI-NCL (62%), J-NCL (36%) and A-NCL (100%) [p=0.05]. Cerebellar
      atrophy was present in: LI-NCL (42%) and J-NCL (55%). Leucoencephalopathy was
      observed in: I- NCL (100%), LI-NCL (65%), J-NCL (45%) and A-NCL (100%)). Thalamic
      T2W-hypointensity was most frequent in I-NCL (80%) followed by J-NCL (36%) and LI
      NCL (23%). This is the largest study of its kind. The presence of
      cerebellar/cerebral atrophy, leucoencephalopathy and thalamic T2W-hypointensity
      in an appropriate clinical setting might provide clues to the diagnosis of NCL:
      leucoencephalopathy and thalamic hypointensity (T2W) were noted more frequently
      in I-NCL, periventricular and parieto-occipital hyperintensities in LI-NCL, and
      cerebellar atrophy in J-NCL. 

PMID- 24029191
TI  - Viper envenomation and cerebral venous thrombosis.

PMID- 24029192
TI  - Current status of multidrug resistant tuberculosis in a tertiary care hospital of
      East Delhi.
AB  - BACKGROUND AND OBJECTIVE: Multidrug resistant tuberculosis (MDR-TB) is caused by
      infection due to Mycobacterium tuberculosis which is resistant to both isoniazid
      (INH) and rifampicin (RIF). It is caused by selection of resistant mutant strains
      due to inadequate treatment and poor compliance. MDR-TB is a major public health
      problem as the treatment is complicated, cure rates are well below those for drug
      susceptible tuberculosis and patient remains infectious for months despite
      receiving the best available therapy. The drug susceptibility pattern of M.
      tuberculosis is essential for proper control of MDR-TB in every health care
      setting, hence the study was initiated with the aim of studying the prevalence of
      MDR-TB in patients attending a tertiary care hospital in east Delhi. MATERIALS
      AND METHODS: Five hundred and forty-three pulmonary and extrapulmonary samples
      from suspected cases of tuberculosis received in the mycobacteriology laboratory
      from November 2009 through October 2010 were investigated for M. tuberculosis.
      All the samples were subjected to direct microscopic examination for
      demonstration of acid fast bacilli followed by culture on Lowenstein-Jensen (LJ)
      medium to isolate M. tuberculosis. Identification was done by conventional
      biochemical methods. Drug susceptibility of isolated M. tuberculosis strains was
      done by conventional 1% proportion method followed by sequencing of RIF resistant
      isolates to detect mutations to confirm resistance. RESULTS AND CONCLUSIONS: M.
      tuberculosis was isolated from 75 out of 543 suspected cases of
      pulmonary/extrapulmonary TB. Three of the total 75 M. tuberculosis isolates (4%)
      showed resistance to any one of the first line drugs. Prevalence of MDR-TB was
      1.3%. The sequencing of single MDR strain showed mutations at codons 516, 517,
      and 518. Amplification of rpoB and sequential analysis of the amplicon is a
      better way of detection of mutation and the evidence of new mutation in this
      study indicate that mutations continue to arise, probably due to the ability of
      M. tuberculosis to adapt to drug exposure.

PMID- 24029193
TI  - Eschar in scrub typhus: a valuable clue to the diagnosis.
AB  - BACKGROUND: Scrub typhus is an acute febrile illness widely prevalent in the
      'tsutsugamushi triangle' region of the world. Clinical features include fever,
      myalgia, headache, rash, and a pathognomonic eschar. An eschar is formed by the
      bite of chigger mite that inoculates the causative agent of Scrub typhus Orientia
      tsutsugamushi. The aim of this study is to determine the most common sites of
      eschars over the bodies of patients with Scrub typhus. MATERIALS AND METHODS: In
      a retrospective analysis, we examined a total of 418 patients who presented to
      Christian Medical College, Vellore between 2009 and 2012 with an acute febrile
      illness and an eschar on clinical examination and confirmed to have scrub typhus
      with a positive Scrub typhus IgM ELISA test. We studied the distribution of
      eschars over the bodies of 418 patients with Scrub typhus. RESULTS: There was a
      significant difference in the distribution of eschars between males and females
      with a preponderance of the chest and abdomen (42.3%) among females and the
      axilla, groin and genitalia (55.8%) in males. Some unusual sites of an eschar
      were the cheek, ear lobe and dorsum of the feet. CONCLUSION: The eschar is the
      most useful diagnostic clue in patients with acute febrile illness in areas
      endemic for Scrub typhus and therefore should be thoroughly examined for its
      presence especially over the covered areas such as the groin, genitalia, infra
      mammary area and axilla.

PMID- 24029194
TI  - Rapid detection of drug resistance and mutational patterns of extensively drug
      resistant strains by a novel GenoType(r) MTBDRsl assay.
AB  - BACKGROUND: The emergence of extensively drug-resistant tuberculosis (XDR-TB) is
      a major concern in the India. The burden of XDR-TB is increasing due to
      inadequate monitoring, lack of proper diagnosis, and treatment. The GenoType (r)
      Mycobacterium tuberculosis drug resistance second line (MTBDRsl) assay is a novel
      line probe assay used for the rapid detection of mutational patterns conferring
      resistance to XDR-TB. AIM: The aim of this study was to study the rapid detection
      of drug resistance and mutational patterns of the XDR-TB by a novel GenoType (r)
      MTBDRsl assay. MATERIALS AND METHODS: We evaluated 98 multidrug-resistant (MDR)
      M. tuberculosis isolates for second line drugs susceptibility testing by 1%
      proportion method (BacT/ALERT 3D system) and GenoType (r) MTBDRsl assay for rapid
      detection of conferring drug resistance to XDR-TB. RESULTS: A total of seven
      (17.4%) were identified as XDR-TB by using standard phenotypic method. The
      concordance between phenotypic and GenoType (r) MTBDRsl assay was 91.7-100% for
      different antibiotics. The sensitivity and specificity of the MTBDRsl assay were
      100% and 100% for aminoglycosides; 100% and 100% for fluoroquinolones; 91.7% and
      100% for ethambutol. The most frequent mutations and patterns were gyrA MUT1
      (A90V) in seven (41.2%) and gyrA + WT1-3 + MUT1 in four (23.5%); rrs MUT1
      (A1401G) in 11 (64.7%), and rrs WT1-2 + MUT1 in eight (47.1%); and embB MUT1B
      (M306V) in 11 (64.7%) strains. CONCLUSIONS: These data suggest that the GenoType
      (r) MTBDRsl assay is rapid, novel test for detection of resistance to second line
      anti-tubercular drugs. This assay provides additional information about the
      frequency and mutational patterns responsible for XDR-TB resistance.

PMID- 24029195
TI  - Course of insight in manic episode.
AB  - BACKGROUND: Insight is an important factor associated with non compliance and
      poor outcome. Poor level of insight has been described as a characteristic in
      patients with acute bipolar disorder with more unawareness in social consequences
      with increasing severity in manic episode. AIM: Main aim of study was to see the
      baseline and longitudinal relationship between dimensions of insight with
      improvement in psychopathology. SETTING AND DESIGN: Forty four patients diagnosed
      with mania, were selected from an inpatient setting at Institute of Mental Health
      and Hospital, Agra with mean age of 31.07(+/-9.00) years. They were assessed at
      base line and were followed up weekly or psychopathology and insight. MATERIALS
      AND METHODS: The Young's mania rating scale for psychopathology and insight was
      assessed on three dimensions of SUMD. RESULTS: Twenty five patients eventually
      completed the study. There was a positive correlation with global insight and
      with psychopathology consistent in longitudinal follow-up (P<0.05), but not
      correlating for awareness for achieved effect of medication and social
      consequences. Linear regression showed a positive relationship at the first and
      second week of assessment of SUMD and YMRS scores (P=0.001; 0.019). CONCLUSION:
      Improvement in insight is graded in a manic episode as compared to
      psychopathology. There is slower improvement in awareness of social consequences
      of mental disorder. It means that improvement in psychopathology may not
      necessarily indicate remission and need further supervision to improve insight
      and hence monitoring.

PMID- 24029197
TI  - Drug resistant tuberculosis: a diagnostic challenge.
AB  - Tuberculosis (TB) is responsible for 1.4 million deaths annually. Wide-spread
      misuse of anti-tubercular drugs over three decades has resulted in emergence of
      drug resistant TB including multidrug-resistant TB and extensively drug-resistant
      TB globally. Accurate and rapid diagnosis of drug-resistant TB is one of the
      paramount importance for instituting appropriate clinical management and
      infection control measures. The present article provides an overview of the
      various diagnostic options available for drug resistant TB, by searching PubMed
      for recent articles. Rapid phenotypic tests still requires days to weeks to
      obtain final results, requiring biosafety and quality control measures. For newly
      developed molecular methods, infrastructure, training and quality assurance
      should be followed. Successful control of drug resistant TB globally will depend
      upon strengthening TB control programs, wider access to rapid diagnosis and
      provision of effective treatment. Therefore, political and fund provider
      commitment is essential to curb the spread of drug resistant TB. 

PMID- 24029196
TI  - Candidemia in intensive care unit patients: a one year study from a tertiary care
      center in South India.
AB  - BACKGROUND: The occurrence of candidemia is on a rise worldwide. Non-albicans
      Candida species have emerged as major causes of candidemia in many countries.
      Added to it is the problem of antifungal resistance in Candida isolates.
      OBJECTIVES: To find out the prevalence of candidemia in our intensive care unit
      (ICU) setup along with the antifungal susceptibility pattern of Candida isolates
      and various risk factors associated with candidemia. MATERIALS AND METHODS: All
      Candida isolates from blood stream infections of ICU patients were included in
      the 1 year study period (November 2008-October 2009). The isolates were speciated
      using various phenotypic tests. Antifungal susceptibility testing was done by
      disk diffusion methods according to Clinical and Laboratory Standards Institute
      guidelines and also using CANDIFAST. Various risk factors associated with the
      development of candidemia were looked into. RESULTS: A total of 39 Candida
      isolates were isolated during the study period of 1 year (prevalence of 0.65%).
      Candida tropicalis (74.35%) was the most common isolate followed by Candida
      albicans, Candida parapsilosis, Candida krusei and Candida glabrata. All the 39
      Candida isolates (100%) were sensitive to amphotericin B while 12 isolates
      (30.8%) were resistant to fluconazole. The risk factors commonly associated with
      candidemia patients were long term antibiotic therapy (64.1%), use of central
      venous catheters (56.4%), urinary catheters (53.9%), steroid therapy (35.9%) and
      diabetes mellitus (33.3%). CONCLUSION: Candidemia is emerging as a significant
      problem in hospitalized patients, especially in ICU setups. Non-albicans Candida
      species are the major cause of candidemia as found in our study and few other
      studies in India. Multicentric studies involving many hospitals are required to
      know the true prevalence of candidemia and the status of antifungal drug
      resistance among Candida isolates in our country.

PMID- 24029198
TI  - Global patterns of seasonal variation in gastrointestinal diseases.
AB  - OBJECTIVES: This study reviewed previous studies to explore the global patterns
      of seasonal variation in gastrointestinal diseases. STUDY DESIGN AND METHODS: A
      series of systematic literature reviews were undertaken to identify studies
      reporting seasonal and monthly data on clinical onset or relapse of
      gastrointestinal diseases (Acute pancreatitis, inflammatory bowel disease, Peptic
      ulcer diseases (PUD), gastroesophageal reflux disease, colon cancer and colonic
      diverticulitis). Thirty-two primary studies (published 1970-2012) from 17
      countries were identified. RESULTS: Upon review of the evidence, it appears that
      the seasonal peaks of PUD are most prominent in colder months while the peak of
      incidence rate of Crohn diseases in most of the countries subjects were found
      during the spring and summer seasons. Seasonal trend in the onset of acute
      pancreatitis exhibits a summer peak in some countries. There were no clearly
      seasonal peaks noted for the ulcerative colitis. CONCLUSIONS: Future experimental
      and observational studies should consider how the environmental factors
      (infection, cold, air pollution etc.) or other triggers (dietary habit, alcohol
      consumption) promotes or hinders such diseases.

PMID- 24029199
TI  - Colistin: re-emergence of the 'forgotten' antimicrobial agent.
AB  - The treatment of the emerging multidrug resistant (MDR) gram-negative organisms
      is a challenge. The development of newer antibiotics has recently slowed down.
      This has led to the re-emergence of the 'old forgotten' antibiotic "Colistin",
      whose use had almost stopped (after 1970's) due to the high incidence of
      nephrotoxicity and neurotoxicity. Colistin (polymyxin E) is a polypeptide
      antibiotic belonging to polymyxin group of antibiotics with activity mainly
      against the gram-negative organisms. Use of colistin has been increasing in the
      recent past and newer studies have shown lesser toxicity and good efficacy.
      Colistin acts on the bacterial cell membrane resulting in increased cell
      permeability and cell lysis. Colistin can be administered orally, topically, by
      inhalational route, intramuscularly, intrathecally, and also intravenously.
      Parenteral Colistin (in the form of colistimethate sodium) has been used to treat
      ventilator-associated pneumonia (VAP) and bacteremia caused by MDR bacteria such
      as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii.
      Inhaled Colistin is used for treating pneumonia/VAP due to MDR gram-negative
      organisms and also used prophylactically in patients with cystic fibrosis. This
      manuscript is a brief review of Colistin and its clinical applications in the
      pediatric population. 

PMID- 24029200
TI  - Hoover's sign.

PMID- 24029201
TI  - Lornoxicam-induced hair loss: an unusual case.
AB  - A patient started on 8 mg lornoxicam twice daily for pain in the hips developed
      acute-onset scalp hair loss. History and clinical examination revealed no evident
      abnormalities. Temporal association of the onset of hair loss with the use of
      lornoxicam, inability to explain hair loss by alternate causes, possibility of
      hair loss with lornoxicam and resolution on dechallenge placed this reaction as a
      probable adverse reaction to lornoxicam. 

PMID- 24029202
TI  - Vesico-cutaneous fistula to the hip: a case report and review of the literature.
AB  - A 37-year-old woman with a vesico-cutaneous hip fistula was admitted to our
      department. The bladder fistula had formed after repeated hip infections. The
      fistula was completely resected and the bladder was repaired using a tension-free
      closure and indwelling catheter for 2 weeks. Vesico-cutaneous fistulae are very
      rare, and their causes can be complex. 

PMID- 24029203
TI  - Primary tracheobronchial amyloidosis: coronal CT scan may provide clues for early
      diagnosis.
AB  - Primary tracheobronchial amyloidosis (PTBA) is a localized form of amyloidosis.
      The clinical signs of this condition are non-specific and diagnosis before
      bronchoscopic examination with multiple biopsies is uncommon. We present three
      cases of PTBA and compare findings between the thoracic imaging and fiberoptic
      bronchoscopy. Radiographic findings often had uncharacteristic features. The
      relatively specific coronal section CT preceded findings in transverse sections,
      and showed an irregular mucosal surface with diffuse prominent nodes and/or
      calcification of the tracheobronchus, which we called the "wavy path sign". In
      conclusion, coronal CT scan can provide ample clues for the early diagnosis of
      PTBA. 

PMID- 24029204
TI  - Development of post-kala-azar dermal leishmaniasis in AmBisome treated visceral
      leishmaniasis: a possible challenge to elimination program in India.
AB  - We report two cases, one male (33 years) and a female (14 years), that developed
      Post-Kala-azar Dermal Leishmaniasis (PKDL) after successful treatment for
      visceral leishmaniasis (VL) or Kala-azar with AmBisome, the lipid complex of
      Amphotericin B. Both cases presented with hypo-pigmented macular lesions all over
      the body. The patients responded well to AmBisome after treatment with three
      courses. This first ever case report from India indicates that possibly there is
      no effective drug for VL until date, which can prevent post-treatment development
      of PKDL. 

PMID- 24029205
TI  - Thyroid storm presenting as congestive heart failure and protein-S deficiency
      induced biventricular and internal jugular venous thrombii.
AB  - The thyroid storm is a medical emergency characterized by decompensation of one
      or more organ systems. Associated cardiac involvement carries poor prognosis.
      Early recognition and appropriate management of life-threatening thyrotoxicosis
      is vital to prevent the high morbidity and mortality that may accompany this
      disorder. We report a young lady presenting with thyroid storm presenting as
      acute heart failure with biventricular and bilateral internal jugular venous
      thrombi. In addition, she also had thyrotoxicosis-induced transient protein-S
      deficiency which recovered following remission. 

PMID- 24029206
TI  - Intraparenchymal pericatheter cyst following disconnection of
      ventriculoperitoneal shunt system.
AB  - Ventriculoperitoneal (VP) shunt is one of the most commonly performed procedures
      in neurosurgery, but it is also the procedure, which is most prone to
      complications. Spread of cerebrospinal fluid (CSF) into the brain parenchyma is a
      rare complication of VP shunt and can take the form of CSF edema or a
      porencephalic cyst. We describe a case of a 11/2-year-old child who presented to
      us with seizures. Computed tomography scan revealed pericatheter porencephalic
      cyst. Surgical exploration revealed a disconnected VP shunt system. Patient was
      neurologically observed after shunt extraction. He was seizure free and
      radiological follow-up showed resolution of cyst. Ours is the first case to
      document the presence of pericatheter cyst following complete disconnection of
      shunt system. Though shunt revision is the accepted treatment modality, careful
      neurological observation can be done after shunt removal especially in
      asymptomatic cases with compensated hydrocephalus. 

PMID- 24029207
TI  - A patient of Russell's viper envenomation presenting with cortical venous
      thrombosis: an extremely uncommon presentation.

PMID- 24029208
TI  - The fish malodor syndrome: a new indication for gastric bypass surgery?

PMID- 24029209
TI  - Great toe gouty tophus-like lesion revealing extensive tendon xanthomatosis in a
      asymptomatic hyperuricemic patient.

PMID- 24029210
TI  - Reversible acute myocardial injury following alcohol bingeing.

PMID- 24029211
TI  - Challenges in the diagnosis and treatment of a case of acute intermittent
      porphyria in India.

PMID- 24029212
TI  - Bilateral putaminal hemorrhagic necrosis with rapid recovery of sensorium in a
      patient with methanol intoxication.

PMID- 24029213
TI  - Imatinib induced pyoderma gangrenosum.

PMID- 24029214
TI  - Acute onset myopia as a presenting feature of systemic lupus erythematosus.

PMID- 24029215
TI  - Black bone marrow aspirate.

PMID- 24029216
TI  - Acute reversible toxic leukoencephalopathy - a different entity.

PMID- 24029217
TI  - Soy milk toxicity: cause for concern.

PMID- 24029218
TI  - Road safety development in Europe: a decade of changes (2001-2010).
AB  - To evaluate the road safety development of a country over time, the percentage
      change in the number of road fatalities is traditionally the main indicator.
      However, simply considering the reduction in the road fatalities may not
      correctly reflect the real improvement in road safety because the transport
      circumstances of a country underlying the road fatalities also change every year.
      In this study, we present a new way for measuring the road safety performance
      change over time, which is to use the technique of data envelopment analysis
      (DEA) and the Malmquist productivity index. In doing so, we can not only focus on
      the evolution of road safety final outcomes within a given period, but also take
      the changes of different measures of exposure in the same period into account. In
      the application, the DEA-based Malmquist productivity index (DEA-MI) is used to
      measure the extent to which the EU countries have improved their road safety
      performance over the period 2001-2010. More objective and insightful results are
      obtained compared to the ones based on the traditional indicator. The results
      show considerable road safety progress in most of the Member States during these
      ten years, and the fatality risk rather than the fatality number on Europe's
      roads has actually been reduced by approximately half. However, the situation
      differed considerably from country to country. The decomposition of the DEA-MI
      into 'efficiency change' and 'technical change' further reveals that the bulk of
      the improvement during the last decade was attained through the adoption of
      productivity-enhancing new technologies throughout the road transport sector in
      Europe, rather than through the relatively underperforming countries catching up
      with those best-performing ones. 

PMID- 24029219
TI  - Very small cerebellar infarcts: integration of recent insights into a functional
      topographic classification.
AB  - BACKGROUND: Very small cerebellar infarcts (diameter <2 cm) are a frequent
      finding on MRI. With an increasing scientific interest in cerebral microinfarcts,
      very small infarcts in the cerebellum deserve more of our attention as well. The
      goal of the present article was to review infarct terminology and mechanisms, as
      well as to critically appraise the current classification system for very small
      cerebellar infarcts. METHODS: A search strategy was designed to identify all
      relevant studies on very small cerebellar infarcts in the English language. This
      search was restricted to papers published up to February 21, 2013. Studies were
      initially identified from the MEDLINE/PubMed database using the search terms
      'small cerebellar infarct', 'lacunar infarct', 'microinfarct', 'end zone
      infarct', 'border zone infarct', 'watershed infarct', 'territorial infarct', and
      'nonterritorial infarct'. Furthermore, a similar search strategy was directed to
      identify all relevant articles on (descriptive and functional) neuroanatomy and
      neuroimaging of the cerebellum. RESULTS: Very small cerebellar infarcts have been
      referred to as lacunar infarcts, as junctional, border zone or watershed
      infarcts, as nonterritorial infarcts, as very small territorial or end zone
      infarcts, or simply as (very) small cerebellar infarcts. Since the original
      clinicoradiological study on these small infarcts, the classification into border
      zones remains in common use. This classification is based upon the assumption
      that these infarcts occur secondary to low flow in between arterial perfusion
      territories, where flow is believed to be the lowest. Later studies, however,
      have suggested occlusion of small (end-) arteries as a prerequisite for the
      pathogenesis of even small cerebellar infarcts, with low flow merely as a
      potential contributor. Therefore, it is likely that infarcts may as well occur in
      a nonborder zone distribution. Moreover, the classification into border zones may
      be considered unreliable since the location of border zones is highly variable
      among individuals and is not known in a particular patient. Recently, a
      functional topographic organization has been found in the cerebellum with
      evidence for a motor-nonmotor dichotomy between the anterior and posterior lobe.
      Since the cerebellar lobes can be easily and reliably distinguished with both CT
      and MRI, we recommend the classification of very small cerebellar infarcts
      according to topographic location. CONCLUSION: There are several fundamental
      concerns with the current classification of very small cerebellar infarcts
      according to border zones, which we would like to overcome by recommending a new
      classification system based on topography. This will allow for a reliable and
      reproducible way of classifying very small cerebellar infarcts and is expected to
      improve clinicoradiological correlation.

PMID- 24029220
TI  - Pulmonary exacerbations in CF patients with early lung disease.
AB  - BACKGROUND: Current definitions of pulmonary exacerbation (PE) in cystic fibrosis
      are based on studies in participants with significant lung disease and may not
      reflect the spectrum of findings observed in younger patients with early lung
      disease. METHODS: We used data from a recent trial assessing the efficacy of
      azithromycin in children to study signs and symptoms associated with PEs and
      related changes in lung function and weight. RESULTS: While increased cough was
      present in all PEs, acute weight loss and reduction in oxygen saturation were not
      observed. Changes in lung function did not differ between subjects who did
      experience a PE and those who were exacerbation-free. CONCLUSIONS: Cough was the
      predominant symptom in CF patients with early lung disease experiencing a PE.
      There was no significant difference in mean 6-month change in lung function or
      weight among subjects with one or more exacerbations and those without an
      exacerbation.

PMID- 24029221
TI  - Drop-out from addiction treatment: a systematic review of risk factors.
AB  - Completion of addiction treatment is one of the most consistent factors
      associated with a favorable treatment outcome. Unfortunately, it is more common
      for a patient to drop-out of addiction treatment than to complete the treatment.
      To prevent drop-out, risk factors must be identified. This box-score review
      focuses on studies investigating the risk factors associated with drop-out from
      addiction treatment published in peer-reviewed journals from 1992 to 2013. A
      total of 122 studies involving 199,331 participants met the inclusion criteria.
      Contrary to recommendations from previous reviews, 91% of the included studies
      focused primarily on enduring patient factors, mainly demographics. The most
      consistent risk factors across the different study designs, samples, and
      measurement methods were cognitive deficits, low treatment alliance, personality
      disorder, and younger age. With the exception of younger age, none of the
      demographic factors emerged as consistent risk factors. Further research on the
      relationship between simple demographic factors and drop-out risk is of limited
      value. However, little is known about the potential risk factors related to
      treatment programs and to the treatment processes. Based on the review, clinical
      recommendations include assessing cognitive functioning and personality disorders
      at baseline and continuous monitoring of treatment alliance. 

PMID- 24029222
TI  - Why proteasome inhibitors cannot ERADicate multiple myeloma.
AB  - Proteasome inhibitors are key parts of our armamentarium against multiple
      myeloma, but the disease can become resistant through poorly defined mechanisms.
      In this issue of Cancer Cell, Leung-Hagesteijn and colleagues describe XBP1s(-)
      subpopulations of tumor cells that are resistant to bortezomib and may account
      for therapeutic failures in the clinic. 

PMID- 24029223
TI  - RASAL2: wrestling in the combat of Ras activation.
AB  - Oncogenic activation of Ras proteins due to missense mutations is frequently
      detected in human cancers but rarely in breast cancer. In this issue of Cancer
      Cell, McLaughlin and colleagues report that ablation of the GasGAP gene, RASAL2,
      is an alternative mechanism by which Ras becomes activated in breast cancer. 

PMID- 24029224
TI  - It takes a CAD to kill a tumor cell with a LMP.
AB  - Cancer cells display lysosome hypertrophy, secreting lysosomal hydrolases for
      tumor progression. Hypertrophy renders lysosomes fragile, increasing lysosomal
      membrane permeabilization (LMP) tendency. In this issue of Cancer Cell, Petersen
      and colleagues show that lysosomal sphingomyelin content determines LMP and
      cationic drugs displace acid sphingomyelinase from lysosomal membranes,
      increasing tumor LMP and death. 

PMID- 24029225
TI  - A Bach2 link between pre-B cell receptor checkpoint and pre-B cell ALL.
AB  - Bach2 is a transcription factor required for affinity maturation of B cells. A
      recent study reveals, quite unexpectedly, that Bach2 also plays a key role in the
      pre-B cell receptor checkpoint and functions as a tumor suppressor in pre-B cell
      acute lymphocytic leukemia. 

PMID- 24029226
TI  - Mechanisms of targeted therapy resistance take a de-TOR.
AB  - The effectiveness of cancer therapeutics targeting signal transduction pathways
      is comprised of a diversity of mechanisms that drive de novo or acquired
      resistance. Two recent studies identify mTOR activation as a point of convergence
      of mechanisms that cause resistance to inhibitors of the Raf-MEK-ERK and PI3K
      signaling. 

PMID- 24029227
TI  - Comment on "Platelet-derived nucleotides promote tumor cell transendothelial
      migration and metastasis via P2Y2 receptor" by Schumacher et al.

PMID- 24029228
TI  - Response to Harper et al.

PMID- 24029229
TI  - Xbp1s-negative tumor B cells and pre-plasmablasts mediate therapeutic proteasome
      inhibitor resistance in multiple myeloma.
AB  - Proteasome inhibitor (PI) resistance mechanisms in multiple myeloma (MM) remain
      controversial. We report the existence of a progenitor organization in primary MM
      that recapitulates maturation stages between B cells and plasma cells and that
      contributes to clinical PI resistance. Xbp1s(-) tumor B cells and pre
      plasmablasts survive therapeutic PI, preventing cure, while maturation arrest of
      MM before the plasmablast stage enables progressive disease on PI treatment.
      Mechanistically, suppression of Xbp1s in MM is shown to induce bortezomib
      resistance via de-commitment to plasma cell maturation and immunoglobulin
      production, diminishing endoplasmic reticulum (ER) front-loading and cytotoxic
      susceptibility to PI-induced inhibition of ER-associated degradation. These
      results reveal the tumor progenitor structure in MM and highlight its role in
      therapeutic failure.

PMID- 24029230
TI  - Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid
      malignancies in mice mimicking human diseases with monosomy 7.
AB  - Monosomy 7 and interstitial deletion of 7q (-7/7q-) are well-recognized nonrandom
      chromosomal abnormalities frequently found among patients with myelodysplastic
      syndromes (MDSs) and myeloid leukemias. We previously identified candidate
      myeloid tumor suppressor genes (SAMD9, SAMD9-like = SAMD9L, and Miki) in the
      7q21.3 subband. We established SAMD9L-deficient mice and found that SAMD9L(+/-)
      mice as well as SAMD9L(-/-) mice develop myeloid diseases resembling human
      diseases associated with -7/7q-. SAMD9L-deficient hematopoietic stem cells showed
      enhanced colony formation potential and in vivo reconstitution ability. SAMD9L
      localizes in early endosomes. SAMD9L-deficient cells showed delays in homotypic
      endosome fusion, resulting in persistence of ligand-bound cytokine receptors.
      These findings suggest that haploinsufficiency of SAMD9L and/or SAMD9 gene(s)
      contributes to myeloid transformation.

PMID- 24029231
TI  - p53 acts as a safeguard of translational control by regulating fibrillarin and
      rRNA methylation in cancer.
AB  - Ribosomes are specialized entities that participate in regulation of gene
      expression through their rRNAs carrying ribozyme activity. Ribosome biogenesis is
      overactivated in p53-inactivated cancer cells, although involvement of p53 on
      ribosome quality is unknown. Here, we show that p53 represses expression of the
      rRNA methyl-transferase fibrillarin (FBL) by binding directly to FBL. High levels
      of FBL are accompanied by modifications of the rRNA methylation pattern,
      impairment of translational fidelity, and an increase of internal ribosome entry
      site (IRES)-dependent translation initiation of key cancer genes. FBL
      overexpression contributes to tumorigenesis and is associated with poor survival
      in patients with breast cancer. Thus, p53 acts as a safeguard of protein
      synthesis by regulating FBL and the subsequent quality and intrinsic activity of
      ribosomes. 

PMID- 24029232
TI  - Protein kinase C alpha is a central signaling node and therapeutic target for
      breast cancer stem cells.
AB  - The epithelial-mesenchymal transition program becomes activated during malignant
      progression and can enrich for cancer stem cells (CSCs). We report that
      inhibition of protein kinase C alpha (PKCalpha) specifically targets CSCs but has
      little effect on non-CSCs. The formation of CSCs from non-stem cells involves a
      shift from EGFR to PDGFR signaling and results in the PKCalpha-dependent
      activation of FRA1. We identified an AP-1 molecular switch in which c-FOS and
      FRA1 are preferentially utilized in non-CSCs and CSCs, respectively. PKCalpha and
      FRA1 expression is associated with the aggressive triple-negative breast cancers,
      and the depletion of FRA1 results in a mesenchymal-epithelial transition. Hence,
      identifying molecular features that shift between cell states can be exploited to
      target signaling components critical to CSCs. 

PMID- 24029233
TI  - The RasGAP gene, RASAL2, is a tumor and metastasis suppressor.
AB  - RAS genes are commonly mutated in cancer; however, RAS mutations are rare in
      breast cancer, despite frequent hyperactivation of Ras and ERK. Here, we report
      that the RasGAP gene, RASAL2, functions as a tumor and metastasis suppressor.
      RASAL2 is mutated or suppressed in human breast cancer, and RASAL2 ablation
      promotes tumor growth, progression, and metastasis in mouse models. In human
      breast cancer, RASAL2 loss is associated with metastatic disease; low RASAL2
      levels correlate with recurrence of luminal B tumors; and RASAL2 ablation
      promotes metastasis of luminal mouse tumors. Additional data reveal a broader
      role for RASAL2 inactivation in other tumor types. These studies highlight the
      expanding role of RasGAPs and reveal an alternative mechanism of activating Ras
      in cancer. 

PMID- 24029234
TI  - Transformation-associated changes in sphingolipid metabolism sensitize cells to
      lysosomal cell death induced by inhibitors of acid sphingomyelinase.
AB  - Lysosomal membrane permeabilization and subsequent cell death may prove useful in
      cancer treatment, provided that cancer cell lysosomes can be specifically
      targeted. Here, we identify acid sphingomyelinase (ASM) inhibition as a selective
      means to destabilize cancer cell lysosomes. Lysosome-destabilizing experimental
      anticancer agent siramesine inhibits ASM by interfering with the binding of ASM
      to its essential lysosomal cofactor, bis(monoacylglycero)phosphate. Like
      siramesine, several clinically relevant ASM inhibitors trigger cancer-specific
      lysosomal cell death, reduce tumor growth in vivo, and revert multidrug
      resistance. Their cancer selectivity is associated with transformation-associated
      reduction in ASM expression and subsequent failure to maintain sphingomyelin
      hydrolysis during drug exposure. Taken together, these data identify ASM as an
      attractive target for cancer therapy.

PMID- 24029235
TI  - SnapShot: Prostate cancer.

PMID- 24029236
TI  - Predominant loss of glutamatergic terminal markers in a beta-amyloid peptide
      model of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is characterized phenotypically by memory impairment,
      neurochemically by accumulation of beta-amyloid peptide (such as Abeta1-42) and
      morphologically by an initial loss of nerve terminals in cortical and hippocampal
      regions. However, it is not known what nerve terminals are mostly affected in
      early AD. We now used a mouse model of AD, based on the intra-cerebral
      administration of soluble Abeta1-42, that leads to memory impairment and loss of
      nerve terminal markers within 2 weeks, to investigate which type of hippocampal
      nerve terminals was mostly affected in the hippocampus. Western blot analysis
      revealed a decrease of the density of vesicular glutamate transporters type 1
      (vGluT1, a marker of glutamatergic terminals; -20.1 +/- 3.6%) and of vesicular
      acetylcholine transporters (vAChT, a marker of cholinergic terminals; -27.2 +/-
      0.9%) but not of vesicular GABA transporters (vGAT, a marker of GABAergic
      terminals) in the hippocampus of Abeta-injected mice. Immunocytochemical analysis
      of single hippocampal nerve terminals revealed that the decrease of the density
      of vGluT1 reflects a reduction of the number of vGluT1-immunopositive nerve
      terminals (-10.6 +/- 3.6%), while no significant changes in the number of vAChT-
      or vGAT-immunopositive nerve terminals were observed. This pilot study shows
      that, in this Abeta-based model of AD, there is an asymmetric loss of different
      synaptic markers with a predominant susceptibility of glutamatergic synapses.
      This article is part of the Special Issue entitled 'The Synaptic Basis of
      Neurodegenerative Disorders'. 

PMID- 24029237
TI  - A new clinical variant of the post-malaria neurological syndrome.
AB  - Post-malaria neurological syndrome (PMNS) is an uncommon, monophasic illness that
      occurs within two months following recovery from Plasmodium falciparum (Pf)
      malaria. Clinical manifestations of PMNS are variable, but published cases
      uniformly feature neurological and/or psychiatric symptoms without long tract
      signs. We describe a case of severe brainstem and spinal cord inflammation with
      paraplegia and sphincter involvement in a 48 year old woman following recovery
      from a Pf malarial illness. We propose that this case represents a previously
      unreported form of PMNS, which has features that distinguish it from acute
      disseminated encephalomyelitis, and that the recognised clinical spectrum of PMNS
      should be extended to include brainstem and spinal cord inflammation.

PMID- 24029239
TI  - Quantitative assessment of Pdx1 promoter activity in vivo using a secreted
      luciferase reporter system.
AB  - The luciferase reporter system is useful for the assessment of various biological
      processes in vivo. The transcription factor pancreatic and duodenal homeobox 1
      (Pdx1) is critical for the formation and the function of pancreatic beta-cells. A
      novel reporter system using secreted Gaussia princeps luciferase (GLuc) under the
      control of a Pdx1 promoter was generated and activated in rat and mouse beta-cell
      lines. This Pdx1-GLuc construct was used as a transgene for the generation of
      reporter mice to monitor Pdx1 promoter activity in vivo via the measurement of
      secreted GLuc activity in a small aliquot of blood. Significantly increased
      plasma GLuc activity was observed in Pdx1-GLuc mice. Analysis of Pdx1-GLuc mice
      by bioluminescence imaging, GLuc reporter assays using homogenates of various
      organs, and immunohistochemistry revealed that GLuc expression and activity were
      exponentially higher in pancreatic beta-cells than in pancreatic non-beta-cells,
      the duodenum, and other organs. In addition, GLuc activity secreted into the
      culture medium from islets isolated from Pdx1-GLuc mice correlated with the
      number of islets. The transplantation of Pdx1-GLuc islets into severe combined
      immunodeficiency mice elevated their plasma GLuc activity. Conversely, a partial
      pancreatectomy in Pdx1-GLuc mice reduced plasma GLuc activity. These results
      suggest that a secreted luciferase reporter system in vivo enables not only the
      monitoring of promoter activity but also a quantitative and minimally invasive
      assessment of physiological and pathological changes in small cell masses, such
      as pancreatic beta-cells. 

PMID- 24029238
TI  - Pancreatic duct ligation after almost complete beta-cell loss: exocrine
      regeneration but no evidence of beta-cell regeneration.
AB  - There has been great interest in the extent of beta-cell regeneration after
      pancreatic duct ligation (PDL) and whether alpha- to beta-cell conversion might
      account for beta-cell regeneration after near-complete beta-cell loss. To assess
      these questions, we established a PDL-model in adult male rats after almost
      complete beta-cell depletion achieved by giving a single high dose of
      streptozocin (STZ) in the fasted state. Because of the resultant severe diabetes,
      rats were given islet cell transplants to allow long-term follow-up. Although
      animals were followed up to 10 months, there was no meaningful beta-cell
      regeneration, be it through replication, neogenesis, or alpha- to beta-cell
      conversion. In contrast, the acinar cell compartment underwent massive changes
      with first severe acinar degeneration upon PDL injury followed by the appearance
      of pancreatic adipocytes, and finally near-complete reappearance of acini. We
      conclude that beta-cells and acinar cells, although originating from the same
      precursors during development, have very distinct regenerative potentials in our
      PDL model in adult rats. 

PMID- 24029240
TI  - Comparative inhibition of the GH/IGF-I axis obtained with either the targeted
      secretion inhibitor SXN101959 or the somatostatin analog octreotide in growing
      male rats.
AB  - Abnormally high GH/IGF-I levels, most often caused by adenomas arising from
      pituitary somatotrophs, generate deleterious effects. We recently described a
      targeted secretion inhibitor (SXN101742) comprising a GHRH domain and the
      endopeptidase domain of botulinum toxin serotype D (GHRH-light chain
      endopeptidase type D domain [LC/D] associated to a heavy chain translocation
      domain [HN]) able to down-regulate the GH/IGF-I axis. In the present study, we
      compared the effect of a single iv bolus of a related molecule developed for
      clinical studies (SXN101959, 1 mg/kg) with a sc infusion of the somatostatin
      analog octreotide (SMS201-995, 10 MUg/kg . h) to lower GH/IGF-I activity in
      growing male rats. Ten days after administration of SXN101959 or initiation of
      the octreotide infusion, body and pituitary weights, body length, GH peaks, and
      IGF-I production were reduced by both treatments but to a greater extent with
      SXN101959. In contrast to unaltered GH gene expression and increased GH storage
      in pituitaries from octreotide-treated rats, the inhibition of GH secretion was
      associated with a collapse of both GH mRNA and protein level in pituitaries from
      SXN101959-treated rats, in line with a specific decrease in hypothalamic GHRH
      production, not observed with octreotide. SXN101959 did not induce major
      apoptotic events in anterior pituitary and exhibited a reversible mode of action
      with full recovery of somatotroph cell functionality 30 days after treatment.
      Octreotide infusion permanently decreased ghrelin levels, whereas SXN101959 only
      transiently attenuated ghrelinemia. Both treatments limited bone mass acquisition
      and altered specifically tissues development. In conclusion, SXN101959 exerts a
      powerful and reversible inhibitory action on the somatotropic axis. Specific
      features of SXN101959, including long duration of action coupled to a strong
      inhibition of pituitary GH synthesis, represent advantages when treating
      overproduction of GH.

PMID- 24029241
TI  - Effects of antenatal synthetic glucocorticoid on glucocorticoid receptor binding,
      DNA methylation, and genome-wide mRNA levels in the fetal male hippocampus.
AB  - The endogenous glucocorticoid (GC) surge in late gestation plays a vital role in
      maturation of several organ systems. For this reason, pregnant women at risk of
      preterm labor are administered synthetic glucocorticoids (sGCs) to promote fetal
      lung development. Animal studies have shown that fetal sGC exposure can cause
      life-long changes in endocrine and metabolic function. We have previously shown
      that antenatal sGC treatment is associated with alterations in global DNA
      methylation and modifications to the hippocampal methylome and acetylome. In this
      study, we hypothesized that: 1) there are changes in the transcriptional
      landscape of the fetal hippocampus in late gestation, associated with the
      endogenous cortisol surge; 2) fetal sGC exposure alters genome-wide transcription
      in the hippocampus; and 3) these changes in transcription are associated with
      modified glucocorticoid receptor (GR) DNA binding and DNA methylation. sGC was
      administered as 2 courses on gestational days (GD) 40, 41, 50, and 51, and the
      hippocampi of fetal guinea pigs were examined before (GD52) and after (GD65) the
      endogenous cortisol surge (Term ~GD67). We also analyzed fetal hippocampi 24
      hours and 14 days following maternal sGC injections (n = 3-4/group). Genome-wide
      modification of transcription and GR DNA binding occurred in late gestation, in
      parallel with the normal GC surge. Further, sGC exposure had a substantial impact
      on the hippocampal transcriptome, GR-DNA binding, and DNA methylation at 24 hours
      and 14 days following the final sGC treatment. These data support the hypothesis
      that GC exposure in late gestation plays a significant role in modifying the
      transcriptional and epigenetic landscape of the developing fetal hippocampus and
      that substantial effects are evident for at least 2 weeks after sGC exposure. 

PMID- 24029242
TI  - Completely humanizing prolactin rescues infertility in prolactin knockout mice
      and leads to human prolactin expression in extrapituitary mouse tissues.
AB  - A variety of fundamental differences have evolved in the physiology of the human
      and rodent prolactin (PRL) systems. The PRL gene in humans and other primates
      contains an alternative promoter, 5.8 kbp upstream of the pituitary transcription
      start site, which drives expression of PRL in "extrapituitary" tissues, where PRL
      is believed to exert local, or paracrine, actions. Several of these
      extrapituitary PRL tissues serve a reproductive function (eg, mammary gland,
      decidua, prostate, etc), consistent with the hypothesis that local PRL production
      may be involved in, and required for, normal reproductive physiology in primates.
      Rodent research models have generated significant findings regarding the role of
      PRL in reproduction. Specifically, disruption (knockout) of either the PRL gene
      or its receptor causes profound female reproductive defects at several levels
      (ovaries, preimplantation endometrium, mammary glands). However, the rodent PRL
      gene differs significantly from the human, most notably lacking the alternative
      promoter. Understanding of the physiological regulation and function of
      extrapituitary PRL has been limited by the absence of a readily accessible
      experimental model, because the rodent PRL gene does not contain the alternative
      promoter. To overcome these limitations, we have generated mice that have been
      "humanized" with regard to the structural gene and tissue expression of PRL.
      Here, we present the characterization of these animals, demonstrating that the
      human PRL transgene is responsive to known physiological regulators both in vitro
      and in vivo. More importantly, the expression of the human PRL transgene is able
      to rescue the reproductive defects observed in mouse PRL knockout (mPRL(-))
      females, validating their usefulness in studying the function or regulation of
      this hormone in a manner that is relevant to human physiology. 

PMID- 24029243
TI  - Mct8-deficient mice have increased energy expenditure and reduced fat mass that
      is abrogated by normalization of serum T3 levels.
AB  - Children with monocarboxylate transporter 8 (MCT8) deficiency lose weight, even
      when adequately nourished. Changes in serum markers of thyroid hormone (TH)
      action compatible with thyrotoxicosis suggested that this might be due to T3
      excess in peripheral tissues. Mct8-deficient mice (Mct8KO) replicate the human
      thyroid phenotype and are thus suitable for metabolic studies so far unavailable
      in humans. In the current work, compared with wild-type (Wt) mice, Mct8KO mice
      were leaner due to reduced fat mass. They tended to use more carbohydrates and
      fewer lipids during the dark phase. Mct8KO mice had increased total energy
      expenditure (TEE) and food and water intake, with normal total activity,
      indicating hypermetabolism. To determine whether this is due to the high serum
      T3, we studied mice deficient in both Mct8 and deiodinase 1 (Mct8D1KO) with serum
      T3 similar to Wt mice and Wt mice given L-T3 to raise their serum T3 to the level
      of Mct8KO mice. Contrary to Mct8KO, Mct8D1KO mice had similar fat mass, TEE, and
      food intake as their D1KO littermates, whereas T3-treated Wt mice showed
      increased food intake and TEE, similar to Mct8KO mice. In skeletal muscle, Mct8KO
      mice had increased T3 content and TH action and increased glucose metabolism,
      which improved in Mct8D1KO mice. These studies indicate that the high serum T3 in
      MCT8 deficiency increases the TEE and fails to maintain weight despite adequate
      calorie intake. This is mediated by tissues that are not predominantly MCT8
      dependent for TH transport, including skeletal muscle. Normalizing serum T3 level
      by deleting deiodinase 1 corrects body composition and the metabolic alterations
      caused by the MCT8 deficiency. 

PMID- 24029244
TI  - Neuroinflammation and central nervous system regeneration in vertebrates.
AB  - Injuries in the central nervous system (CNS) are one of the leading causes of
      mortality or persistent disabilities in humans. One of the reasons why humans
      cannot recover from neuronal loss is the limited regenerative capacity of their
      CNS. By contrast, non-mammalian vertebrates exhibit widespread regeneration in
      diverse tissues including the CNS. Understanding those mechanisms activated
      during regeneration may improve the regenerative outcome in the severed mammalian
      CNS. Of those mechanisms, recent evidence suggests that inflammation may be
      important in regeneration. In this review we compare the different events
      following acute CNS injury in mammals and non-mammalian vertebrates. We also
      discuss the involvement of the immune response in initiating regenerative
      programs and how immune cells and neural stem/progenitor cells (NSPCs)
      communicate. 

PMID- 24029245
TI  - Factors predicting late recurrence for estrogen receptor-positive breast cancer.
AB  - BACKGROUND: Adjuvant endocrine therapy beyond 5 years reduces recurrence in
      patients with estrogen receptor-positive breast cancer. We have previously shown
      that immunohistochemical markers (IHC4) and two gene expression profile tests
      (recurrence score [RS] and PAM50 risk of recurrence [ROR]) are associated with
      time to distant recurrence, and we have now assessed the value of each of these
      scores and routine clinical variables for predicting outcome, specifically in
      years 5 to 10. METHODS: We used univariate and multivariable proportional hazards
      models to determine the prognostic value of all variables and scores (IHC4, RS,
      ROR) for distant recurrence, separately in years 0 to 5 and specifically for
      years 5 to 10 for all patients. All statistical tests were two-sided. RESULTS:
      Nodal status and tumor size were at least as strong in years 5 to 10 as in years
      0 to 5 (nodal status, years 5-10: chi2 = 21.72 vs years 0-5: chi2 = 11.08, both P
      < .001; tumor size, years 5-10: chi2 = 10.52 vs years 0-5: chi2 = 10.82, both P =
      .001). Ki67 and the overall IHC4 score were the only statistically significant
      biomarkers related to distant recurrence univariablely in the 5 to 10 year period
      (chi2 = 8.67, chi2 = 13.22, respectively). The ROR score was the strongest
      molecular prognostic factor in the late follow-up period (chi2 = 16.29; P <
      .001), whereas IHC4 (chi2 = 7.41) and RS (chi2 = 5.55) were only weakly
      prognostic in this period. Similar results were seen for all subgroups and for
      all recurrences. CONCLUSIONS: None of the IHC4 markers provided statistically
      significant prognostic information in years 5 to 10, except for nodal status and
      tumor size. ROR gave the strongest prognostic information in years 5 to 10. These
      results may help select patients who could benefit most from hormonal therapy
      beyond 5 years of treatment.

PMID- 24029246
TI  - Explanatory models of somatoform disorder patients attending a psychiatry
      outpatient clinic: a study from North India.
AB  - BACKGROUND: The symptoms of somatoform disorders are very distressing to the
      sufferer as well as pose significant burden on the health-care delivery system.
      Although the nature of symptoms is physical, the underlying mechanisms are not
      clearly understood. OBJECTIVE: The purpose of this study was to assess the
      explanatory models of patients with somatoform disorders presenting to a tertiary
      care hospital in Northern India. METHOD: A total of 99 consecutive adult patients
      (>= 18 years) with diagnosis of somatoform disorders according to the
      International Classification of Diseases-10th Revision (ICD-10) were evaluated
      for their explanatory models using the causal models section of Explanatory Model
      Interview Catalogue (EMIC). RESULTS: The mean age of the study sample was 36.52
      years, and the mean duration of illness was 59.39 +/- 57.68 months. The most
      common clinical diagnosis was that of persistent somatoform pain disorder. The
      most common explanations given belonged to the category of psychological factors
      (68.7%) followed by weakness (67.7%), social causes (51%) and karma-deed-heredity
      (53.5%) category. The mean number of etiological categories reported were 2.6
      (standard deviation (SD) = 1.7). Among the various specific causes, the commonly
      reported explanations by one half of the sample in decreasing order were general
      weakness (63.6%), mind-thoughts-worry category (59.6%) and loneliness (53.5%).
      The mean number of specific etiologies was 4.9 (SD = 3.83). CONCLUSION: Most of
      the patients with somatoform disorder attribute their symptoms to psychological
      factors. It also becomes imperative to understand the physical symptoms in
      somatoform disorders from the sociocultural aspects of patients.

PMID- 24029247
TI  - Impact of personality temperaments and characters on academic performance and
      specialty selection among a group of Egyptian medical graduates.
AB  - BACKGROUND: The relationship between personality temperaments, academic
      achievement and specialty interest is important because of its implications in
      career counseling. AIM: To assess the effect of personality on academic
      performance and career selection and to study the impact of some sociodemographic
      factors on academic achievement and career choice of medical graduates.
      METHODOLOGY: A total of 436 medical graduates of Ain Shams medical school were
      approached, out of which 331 participated. They were given a sociodemographic
      questionnaire, and the Temperament and Character Inventory-Revised (TCI-R; 240)
      for personality construct; they had to answer questions about academic
      achievement, ranking, scores and choice of medical specialty. RESULTS: Novelty
      seeking (NS1, NS2 and NS3) and self-transcendence (ST1 and ST2) were correlated
      with graduation ranking, (r = .2, p = .00; r = .15, p = .009; r = .16, p = .005;
      r = .12, p = .003; r = .14, p = .02; r = .17, p = .004; r = .13, p = .03,
      respectively), that is, lower NS and ST had better academic outcome. Only high
      school score was associated with better achievement (p = .00). In specialty
      selection, females were significantly overrepresented in pediatrics and clinical
      pathology, whereas males were significantly predominating surgical specialties
      except for obstetrics and gynecology (p = .00). Students choosing patient
      centered specialties had higher reward dependence (RD), persistence (PS) and
      cooperativeness (C); those choosing clinical pathology had highest harm avoidance
      (HA), whereas those choosing radiology had lowest HA and those choosing surgery
      had significantly higher self-directedness (SD3). CONCLUSION: Personality impacts
      academic achievement and specialty choice with other factors as gender and
      previous scholastic performance.

PMID- 24029249
TI  - Ethnomedicinal plants used for treating epilepsy by indigenous communities of sub
      Himalayan region of Uttarakhand, India.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Although many plants are claimed to possess
      anticonvulsant/antiepileptic (AC/AE) properties, but there is very little
      information available about plants used by various ethnic communities in
      different parts of India to treat epilepsy, one of the most common disorders of
      central nervous system (CNS); this communication provides significant
      ethnomedicinal information on the plants used by indigenous communities: Bhoxa,
      Tharu and nomadic Gujjars of sub-Himalayan region, Uttarakhand, India to treat
      epilepsy, so that it could be used as a baseline data for studying chemical
      constituents and biological activities of these promising plants. AIMS OF THE
      STUDY: To record herbal preparations used by the presently studied communities
      for treating epilepsy and discuss AC/AE properties of the recorded plants.
      RESEARCH STRATEGY AND METHODS: Ninety one traditional healers (29 Bhoxa, 35 Tharu
      and 27 nomadic Gujjars) in sub-Himalayan region of Uttarakhand, India were
      interviewed to collect information on herbal preparations used by them for
      treating epilepsy. For each recorded species the use value (UV) and fidelity
      level (FL) was calculated. RESULTS: A total of 24 plants belonging to 24 genera
      and 22 families were used by the presently studied communities in 26 formulations
      to treat epilepsy. According to FL and UV values, most preferred species for the
      treatment of epilepsy by Bhoxa community are Ricinus communis L. and Datura
      stramonium L.; by nomadic Gujjar community are Martynia annua L., Bacopa monnieri
      (L.) Wettst. and Ricinus communis L.; and by Tharu community are Allium sativum
      L., Asparagus racemosus Willd. and Achyranthes aspera L. Eight plants viz.,
      Allium sativum L., Boerhavia diffusa L., Cassia fistula L., Clerodendrum viscosum
      Vent., Datura stramonium L., Inula cappa DC., Oroxylum indicum (L.) Kurz and
      Pavetta indica L. recorded in the present survey have been reported for the first
      time in treatment of epilepsy by these indigenous communities in India. Five out
      of these eight newly reported plants viz., Cassia fistula L., Clerodendrum
      viscosum Vent., Inula cappa DC., Oroxylum indicum (L.) Kurz and Pavetta indica L.
      have not been pharmacologically evaluated yet for their possible AC/AE
      properties. CONCLUSIONS: Detailed research on the listed plants and their
      derivatives may be undertaken to provide new alternative treatments and
      therapeutic uses for epilepsy or other diseases of CNS. We hope that this article
      will stimulate further investigations into natural products for new AC/AE agents
      from the recorded ethnomedicinal plants.

PMID- 24029248
TI  - Precursors of adolescent substance use from early childhood and early
      adolescence: testing a developmental cascade model.
AB  - This study examined developmentally salient risk and protective factors of
      adolescent substance use assessed during early childhood and early adolescence
      using a sample of 310 low-income boys. Child problem behavior and proximal family
      risk and protective factors (i.e., parenting and maternal depression) during
      early childhood, as well as child and family factors and peer deviant behavior
      during adolescence, were explored as potential precursors to later substance use
      during adolescence using structural equation modeling. Results revealed that
      early childhood risk and protective factors (i.e., child externalizing problems,
      mothers' depressive symptomatology, and nurturant parenting) were indirectly
      related to substance use at the age of 17 via risk and protective factors during
      early and middle adolescence (i.e., parental knowledge and externalizing
      problems). The implications of these findings for early prevention and
      intervention are discussed. 

PMID- 24029250
TI  - SDF7, a group of Scoparia dulcis Linn. derived flavonoid compounds, stimulates
      glucose uptake and regulates adipocytokines in 3T3-F442a adipocytes.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Adipocytes are major tissues involved in glucose
      uptake second to skeletal muscle and act as the main adipocytokines mediator that
      regulates glucose uptake mechanism and cellular differentiation. The objective of
      this study were to examine the effect of the SDF7, which is a fraction consists
      of four flavonoid compounds (quercetin: p-coumaric acid: luteolin: apigenin=8:
      26: 1: 3) from Scoparia dulcis Linn., on stimulating the downstream components of
      insulin signalling and the adipocytokines expression on different cellular
      fractions of 3T3-F442a adipocytes. MATERIAL AND METHODS: Morphology and lipid
      accumulation of differentiated 3T3-F442a adipocytes by 100 nM insulin treated
      with different concentrations of SDF7 and rosiglitazone were examined followed by
      the evaluation of glucose uptake activity expressions of insulin signalling
      downstream components (IRS-1, PI3-kinase, PKB, PKC, TC10 and GLUT4) from four
      cellular fractions (plasma membrane, cytosol, high density microsome and low
      density microsome). Next, the expression level of adipocytokines (TNF-alpha,
      adiponectin and leptin) and immunoblotting of treated 3T3-F442 adipocytes was
      determined at 30 min and 480 min. Glucose transporter 4 (GLUT4) translocation of
      3T3-F442a adipocytes membrane was also determined. Lastly, mRNA expression of
      adiponectin and PPAR-gamma of 3T3-F442a adipocytes were induced and compared with
      basal concentration. RESULTS: It was found that SDF7 was able to induce
      adipocytes differentiation with great extends of morphological changes, lipid
      synthesis and lipid stimulation in vitro. SDF7 stimulation of glucose transport
      on 3T3-F442a adipocytes are found to be dose independent, time-dependent and
      plasma membrane GLUT4 expression-dependent. Moreover, SDF7 are observed to be
      able to suppress TNF-alpha and leptin expressions that were mediated by 3T3-F442a
      adipocytes, while stimulated adiponectin secretion on the cells. There was a
      significant expression (p<0.01) of protein kinase C and small G protein TC10 on
      3T3-F442a adipocytes upon treatment with SDF7 as compared to the control. SDF7
      was also found to be effective in stimulating adiponectin and PPAR-gamma mRNA
      upregulation at 50 ug/ml. CONCLUSION: SDF7 exhibited good lipogenesis,
      adiponectinesis and glucose uptake stimulatory properties on 3T3-F442a
      adipocytes.

PMID- 24029251
TI  - Local electron beam excitation and substrate effect on the plasmonic response of
      single gold nanostars.
AB  - We performed cathodoluminescence (CL) spectroscopy and imaging in a high
      resolution scanning electron microscope to locally and selectively excite and
      investigate the plasmonic properties of a multi-branched gold nanostar on a
      silicon substrate. This method allows us to map the local density of optical
      states from the nanostar with a spatial resolution down to a few nanometers. We
      resolve, both in the spatial and spectral domain, different plasmon modes
      associated with the nanostar. Finite-difference time-domain (FDTD) numerical
      simulations are performed to support the experimental observations. We
      investigate the effect of the substrate on the plasmonic properties of these
      complex-shaped nanostars. The powerful CL-FDTD combination helps us to understand
      the effect of the substrate on the plasmonic response of branched nanoparticles. 

PMID- 24029252
TI  - New-onset diabetes after transplantation--role of oral glucose tolerance test for
      diagnosis and study of risk factors.
AB  - To determine the role of the oral glucose tolerance test in the early detection
      of new-onset diabetes after transplantation (NODAT) and to compare the various
      risk factors and insulin kinetics in the transplant patients, we studied 41 live
      related renal allograft recipients who were not diabetic before transplantation.
      Immunosuppression included triple drug therapy (cyclosporine, azathioprine and
      steroids) and rejection episodes were treated with methyl prednisolone (30 mg/kg
      IV * 3 days). All the study patients were subjected to an oral glucose tolerance
      test (OGTT) at Day 90 post-transplant and classified as having normal glucose
      tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT)
      and NODAT as per the World Health Organization guidelines. Insulin levels were
      also determined at 0, 1/2 hour, 1 hour and 2 hours during OGTT. NODAT was noted
      in 29.2% of the study patients, IFG in 4.8% of the study patients and NGT in
      65.8% of the study patients. All the groups had normal fasting plasma glucose,
      but higher than normal insulin levels, suggesting insulin resistance. The
      patients with overt NODAT had, in addition, low fasting insulin (insulin
      secretory defect). OGTT may be used for the early detection of NODAT. Although
      insulin resistance is detected in the majority of post-transplant patients, NODAT
      also reveals also an insulin secretory defect. 

PMID- 24029253
TI  - Characteristics and prognosis of lymphoproliferative disorders post-renal
      transplantation in living versus deceased donor allograft recipients.
AB  - In this study, we compared the features and prognosis of post-transplantation
      lymphoproliferative disorders (PTLD) occurring in living donor recipients with
      those of deceased donor kidney transplant patients. A comprehensive search was
      performed for finding studies reporting data of PTLD in living and deceased donor
      renal recipients in the Pubmed and Google scholar search engines. Finally,
      international data from 14 different studies were included in the analysis.
      Overall, 122 renal recipients with PTLD were entered into this analysis. Chi
      square test showed that renal recipients from living donors significantly less
      frequently represented any remission episodes during the course of their disease
      (41% vs. 63%, respectively; P = 0.05). Living donor renal recipients were
      significantly more likely to develop metastasis in comparison with deceased donor
      recipients (64% vs. 23%, respectively; P = 0.035). Histopathological evaluations
      were comparable between the two patient groups. Survival analysis did not show
      any difference between the patient groups, even when patients were adjusted for
      the type of immuno-suppression. The mortality rate of the transplant patients
      with PTLD was 55.3% and the 1- and 5-year patients survival rates were 50% and
      37%, respectively, for the deceased donor renal recipients compared with 60% and
      34%, respectively, for the living donors group. We conclude that living donor
      kidney transplant recipients who develop PTLD have a higher rate of metastasis
      and a lower rate of remission episodes. Further prospective studies with a large
      patient population are needed to confirm our results. 

PMID- 24029254
TI  - Safety and efficacy of everolimus in chronic allograft nephropathy.
AB  - Chronic allograft nephropathy (CAN) is a major cause of late kidney allograft
      loss. Everolimus, a novel proliferation signal inhibitor, ameliorates CAN by its
      antiproliferative or apoptosis-enhancing effects. This study aims to evaluate the
      safety and efficacy of everolimus in renal transplant recipients with calcineurin
      inhibitor (CNI) withdrawal either due to CAN or cal-cineurin inhibitor toxicity
      (CNIT). A total 21 patients with CAN or CNIT converted from CNI to everolimus
      were prospectively studied from 2006 to 2009. There were 19 males and two
      females, with a mean age of 32.9 +/- 10.7 years. Eight patients had chronic
      interstitial nephritis, three had diabetes mellitus, nine had end-stage renal
      disease and one had focal segmental glomerulosclerosis as native kidney disease.
      The mean duration of dialysis was 10.7 +/- 7 months. 57.2% of the patients had
      CAN and 42.8% had CNIT. Everolimus was started within six months of post
      transplantation in six patients, within 6-12 months in two patients, within 1-2
      years in four patients and after more than 2 years in nine patients. The mean
      dose at first month was 1.25 mg/day, at six month was 1.028 +/- 0.3 mg/day and at
      12 th month was 0.97 +/- 0.2 mg/day, with a mean trough level of 6.35 +/- 3
      ng/dL, 5.18 +/- 3 ng/dL and 6.43 +/- 1.7 ng/dL, respectively. At the 12 th month,
      serum creatinine declined from 2.07 +/- 0.58 mg/dL to 1.65 +/- 0.81 mg/dL. The
      mean calculated glomerular filtration rate improved from 40.85 +/- 8.8 mL/min to
      56.84 +/- 11.4 mL/min. No major side-effects were observed. Everolimus along with
      mycophenolate mofetil or azathioprine and prednisolone as a maintenance
      immunosuppressive therapy was found to be effective and safe in patients with
      CNIs withdrawal either due to CAN or CNIT. 

PMID- 24029255
TI  - Effect of chronic hepatitis C virus infection on bone mineral density in
      pediatric renal transplant recipients.
AB  - Previous studies have suggested that loss of bone mineral density (BMD)
      frequently occurs in patients with chronic viral liver disease, presenting with
      histologically proven liver cirrhosis. However, little is known about the
      occurrence of bone disease in non-cirrhotic patients with chronic hepatitis C
      virus (HCV) infection. Furthermore, to the best of our knowledge, such an effect
      has never been studied in pediatric renal transplant recipients. The aim of this
      study was to assess the impact of HCV infection on BMD in pediatric renal
      transplant patients. We performed a cross-sectional study to assess BMD and HCV
      in 83 patients who received living renal allotransplants in the Mansoura Urology
      and Nephrology Center between 1983 and 2005. The mean age of the study patients
      at transplantation was 13.4 +/- 2.9 years; there were 53 males (63.9%) and 30
      females (36.1%). BMD was studied using dual energy X-ray absorptiometry at
      various time intervals up to 16 years after transplantation (mean duration after
      transplantation was 48 +/- 34 months, range 12- 192 months). Thirty-three
      patients tested positive for HCV-RNA (positive group) and 50 patients were
      negative (negative group), and we compared the BMD between the two groups. Before
      transplantation, 58 patients (69.9%) were on maintenance hemodialysis, four
      (4.8%) were on peritoneal dialysis and 21 (25.3%) were pre-emptive. Among the HCV
      positive group, six patients (18.2%) had osteoporosis, 17 (51.5%) had osteopenia
      and ten (30.3%) had normal BMD. In the HCV-negative group, ten patients (20.0%)
      had osteoporosis, 24 (48.0%) had osteopenia and 16 (32.0%) had normal BMD. The
      difference was not significant between the two groups (P = 0.9). Also, there was
      no significant difference in the serum creatinine, calcium, phosphorus and
      parathormone levels between the two groups. Our results suggest that chronic HCV
      infection does not pose a risk for low BMD in pediatric renal transplant
      recipients. 

PMID- 24029256
TI  - Progressive pulmonary hypertension: another criterion for expeditious renal
      transplantation.
AB  - The aim of this retrospective study was to compare the prevalence of pulmonary
      hypertension in a cohort of patients with end-stage renal disease (ESRD) prior to
      and following renal transplantation and to identify the possible risk factors. Of
      the 425 renal transplantations performed between 2001 and 2007, Doppler
      echocardiographic findings were available in 124. The echocardiographic data,
      collected both pre- and post-transplant, included the pulmonary artery pressure
      (PAP), ejection fraction and left ventricular hypertrophy. The data analyzed
      included age, gender, hypertension, diabetes, smoking status, along with blood
      urea, creatinine, glomerular filtration rate, hemoglobin, hemodialysis duration,
      urine albumin, arterio-venous access and body mass index (BMI). Chi-square test
      was used for discrete variables and ANOVA was used for continuous variables. Of
      the patients studied, males comprised 72%; the mean age was 43.3 +/- 13.02 years;
      87% were hypertensive, 30% were diabetic and 4% were smokers. Statistical
      analysis revealed a significant reduction of the PAP, irrespective of its
      severity, following renal transplantation (P <0.05). The PAP had no significant
      correlation with any of the parameters analyzed, with the exception of BMI (P
      <0.05). Our study suggests that the PAP gets reduced in patients with ESRD after
      renal transplantation. 

PMID- 24029257
TI  - Relation of middle molecules levels and oxidative stress to erythropoietin
      requirements in high-flux versus low-flux hemodialysis.
AB  - The objective of this study is to investigate the serum beta-2-microglobulin
      (B2MG) and advanced oxidation protein products (AOPP) as middle molecule uremic
      toxins and protein carbonyl (PCO) as oxidative stress marker in uremic patients
      undergoing high-flux versus low-flux hemodialysis (HD) and to correlate their
      levels to the erythropoietin requirements for those patients. Twenty patients on
      chronic low-flux HD were recruited in the study. At the start of the study, all
      patients underwent high-flux HD for eight weeks, followed by low-flux HD for two
      weeks as a washout period. The patients were then subjected to another eight
      weeks of low-flux HD. Blood samples were obtained at the beginning and at the end
      of the high-flux period and the low-flux period. The mean erythropoietin dose for
      patients using high-flux HD was significantly lower than that for low-flux HD (P
      = 0.0062). Post-high flux, the B2MG and PCO levels were significantly lower than
      the pre-high-flux levels (P = 0.026 and 0.0005, respectively), but no significant
      change was observed in AOPP (P = 0.68). Post-low flux, the B2MG, AOPP and PCO
      were significantly higher than the pre-low-flux levels (P = 0.0002, 0.021 and
      <0.0001, respectively). Post-low flux, the B2MG and PCO were significantly higher
      than the post-high-flux levels (P <0.0001), but no significant difference was
      observed in AOPP (P = 0.11). High-flux HD results in reduction of some of the
      middle molecule toxins and PCO levels better than low-flux HD, and is associated
      with a better response to erythropoietin. 

PMID- 24029258
TI  - Clinical presentation and etiology of osteomalacia/rickets in adolescents.
AB  - This study was conducted to determine the causes and clinical presentations of
      osteomalacia/rickets in adolescents seen at the King Abdulaziz Medical City
      (KAMC), Riyadh. Because osteomalacia and rickets constitute the same entity, the
      term osteomalacia will be used for future discussion. A retrospective file review
      was performed on all adolescents (10-16 years) with osteomalacia, defined as
      alkaline phosphatase levels >=500 IU/L, seen at the KAMC, Riyadh, from 2000 to
      2006. We recorded the signs and symptoms, dietary history and amount of sun
      exposure at presentation. A total of 135 patients were found to fit the inclusion
      criteria for the study. Of them, 57 had nutritional causes, with a mean age of
      13.2 years, and included 32 females. At diagnosis, 22 patients were found to have
      bone pain, 10 had bone deformities, eight had pathological fractures and 17 were
      asymptomatic. Secondary causes for osteomalacia were found in 59 cases who had
      liver and renal disease and in 19 other patients who were on medications such as
      anticonvulsants and steroids, which are known to cause osteomalacia. Our study
      indicates that osteomalacia is a significant health burden that deserves special
      attention. Bone pain is the most common presenting symptom at diagnosis. Because
      of the high risk of osteomalacia associated with the use of anticonvulsants and
      steroids, it is advised that all patients on these drugs should be routinely
      screened for secondary osteomalacia. 

PMID- 24029259
TI  - Peritubular capillaries and renal function in pediatric idiopathic nephrotic
      syndrome.
AB  - Nephrotic syndrome (NS) is a common renal disorder with significant tubulo
      interstitial damage due to the combined effects of proteinuria and obstruction of
      efferent blood flow. Peritubular capillary (PTC) loss has also been correlated
      with interstitial fibrosis. This study included 30 pediatric cases of idiopathic
      NS. Clinical details, including biochemical parameters, were recorded and renal
      biopsy slides were reviewed for histological features. PTCs were highlighted
      using anti-CD34 antibody and quantified with the help of image analysis software.
      Postmortem kidney biopsies from seven children were taken as controls for
      quantification of PTCs and interstitial fibrosis. Wherever possible, as
      ultrastructural examination of the renal biopsy was performed. Appropriate
      statistical methods were applied. Patients with minimal change disease (MCD) had
      lower serum creatinine as compared with those with focal and segmental
      glomerulosclerosis (FSGS). Similarly, tubular atrophy and interstitial fibrosis
      were significantly lower in MCD than in FSGS. PTC density was lower in all groups
      of NS as compared with the controls. Biopsies with FSGS had a lower PTC density
      compared with both MCD and mesangioproliferative glomerulonephritis. PTC density
      showed a negative correlation with serum creatinine and degree of proteinuria.
      PTC loss appears to play an important role in the development of renal biopsy
      changes in pediatric NS. This aspect of the renal vasculature requires further
      study in idiopathic NS. 

PMID- 24029260
TI  - Incidence and clinical outcome of renal amyloidosis: a retrospective study.
AB  - The kidneys are affected in almost all patients with amyloid A in secondary
      amyloidosis (AA) amyloidosis but less frequently in immunoglobulin light chains
      in primary systemic amyloidosis (AL) amyloidosis. In this study, we present the
      incidence, etiology, clinical manifestations, biochemical features and clinical
      course of renal amyloidosis. We conducted a retrospective study on a group of 40
      cases with renal biopsy-proven amyloidosis. They constituted 2.5% of the total
      cases of renal biopsies performed in the Theodor Bilharz Research Institute,
      Cairo, Egypt, during the period from February 2003 to May 2009. The mean age (30
      males, ten females) was 36.51 +/- 10.32 years. Thirty-two of the cases had
      secondary AA amyloidosis and eight cases had primary AL amyloidosis. The causes
      of secondary amyloidosis were as follows: 12 (30%) familial Mediterranean fever
      (FMF), eight (20%) pulmonary tuberculosis, four (10%) chronic osteomyelitis, four
      (10%) bronchiectasis, three (7%) rheumatoid arthritis and one (2%) rheumatic
      heart disease. The eight cases of primary AL amyloidosis comprised of five cases
      that were associated with myloma (13%) and three (8%) cases that were idiopathic.
      Among the 23 patients with AA amyloidosis, after six months of treatment with
      colchicine, the proteinuria improved, serum albumin level increased and edema
      disappeared in 13 patients. In four cases of AA amyloidosis who were clinically
      and biochemically normal after cholchicine therapy, a second renal biopsy
      disclosed decreased amyloid deposition compared with the first biopsy. In the
      three renal transplanted patients who had amyloidosis secondary to FMF and were
      treated with colchicines, AA amyloidosis did not recur in the transplanted
      kidney. It might be possible that in AL amyloidosis, treatment with methotrexate,
      melphalan and prednisolone may improve survival. The incidence of renal
      amyloidosis is increasing and colchicine can be used in secondary amyloidosis as
      it may have an effect on reducing the production of the amyloid precursor
      proteins and in reducing proteinuria. 

PMID- 24029261
TI  - Role of expression of endothelin-1 and angiotensin-II and hypoxia-inducible
      factor-1alpha in the kidney tissues of patients with diabetic nephropathy.
AB  - The objective of this study was to detect the expression of Angiotensin-II (Ang
      II), Hypoxia-inducible factor-1alpha (HIF-1alpha) and Endothelin-1 (ET-1) in the
      kidneys of patients with diabetic nephropathy (DN) and to investigate their
      relationship with renal interstitial fibrosis (RIF). A total of 47 paraffin
      specimens of patients with DN and six controls were enrolled in this study, and
      all were diagnosed by histopathology. We studied the expressions of Ang-II, HIF
      1alpha and ET-1 by immuno-histochemical staining and the level of RIF by Masson
      staining. The following results were found: (a) RIF existed in the kidneys of
      patients with DN, (b) the expressions of Ang-II, HIF-1alpha and ET-1 were lower
      in the control group but increased significantly in the DN group, (c) the
      expression of Ang-II, HIF-1alpha and ET-1 in tubular epithelial cells directly
      correlated with RIF (r s = 0.659, 0.633, 0.716, P <0.01) and (d) the expression
      of Ang-II, ET-1 and HIF-1alpha in the kidneys of patients with DN positively
      correlated with serum creatinine (Scr) levels (r s = 0.391, 0.594, 0.531, P
      <0.01) but they did not correlate with the 24-h urinary protein, blood glucose
      and serum albumin levels. These results provide new insights suggesting that over
      expression of Ang-II, HIF-1alpha and ET-1 promote the progression of RIF in DN.
      Thus, targeting reduction in the expression of Ang-II, HIF-1alpha and ET-1 can
      delay RIF in DN. Further studies are needed to validate this observation. 

PMID- 24029262
TI  - A kink in transplantation: a rare cause of early graft dysfunction.
AB  - Kink of the transplant renal artery is a rare yet correctable cause of early
      graft dysfunction. We describe a 35-year-old male patient with end-stage renal
      disease who underwent live, related renal transplantation with end-to-side
      anastomosis of the graft vessels with the external iliac vessels. He had oliguria
      and uncontrolled hypertension in the post-operative course and was found to have
      a parvus tardus waveform on Doppler ultrasound and an acute angled kink of the
      renal artery on angiography. After failure of initial attempts at per cutaneous
      transluminal renal angioplasty, the patient was re-explored and the graft renal
      artery was anastomosed with the internal iliac artery. The patient had a steady
      recovery and was discharged with a good renal function. A kinking of the renal
      artery should be excluded when early graft dysfunction is associated with a
      parvus tardus waveform. 

PMID- 24029263
TI  - Combined liver and kidney transplantation in primary hyperoxaluria: a report of
      three cases and review of the literature.
AB  - Primary hyperoxaluria type-1 (PH-1) is a rare autosomal recessive metabolic
      disorder leading to excessive oxalate production, deposition of calcium oxalate
      crystals in the kidney, nephrocalcinosis, progressive renal failure and systemic
      deposition of oxalate (oxalosis). Combined liver and kidney transplantation
      (LKT), which has been accepted as the treatment of choice for PH-1, has
      considerably improved patient and graft survival. Herein, we report our
      experience of three children with PH-1 who underwent combined LKT, with a review
      of the literature. 

PMID- 24029264
TI  - Late response to rituximab in a dialysis patient with severe lupus nephritis.
AB  - Although recently completed controlled trials failed to demonstrate a significant
      effect of rituximab on the clinical outcome in non-renal and renal lupus, there
      is growing evidence from case reports and open-label trials that the use of this
      medication is successful in certain subgroups of patients including refractory
      cases and helps in reducing the dose of steroids. We present a 26-year-old female
      who failed to respond to a long-course treatment with prednisolone,
      cyclophosphamide, mycophenolate mofetil and azathioprine and who went on to
      develop end-stage renal disease requiring commencement of regular maintenance
      hemodialysis. Ten days before starting dialysis, she was given rituximab, and a
      second dose was given 17 days after starting dialysis. After 7 months on
      dialysis, the patient began to regain kidney function and is now off dialysis for
      11 months. To the best of our knowledge, this is the first case report of a lupus
      patient on dialysis treated with rituximab in whom dialysis could be stopped and
      who remained off this therapy up till now, after an observation period of 1 year.

PMID- 24029265
TI  - Ergotamine-induced acute tubulo-interstitial nephritis.
AB  - Ergotamine has been used for the treatment of migraine for many years, and its
      use in adults is considered to be safe and effective. In this report, we present
      a 22-year-old female patient, a known case of migraine, who was on ergotamine
      tartrate and presented with hypertension and renal failure. Renal biopsy
      indicated features of acute tubulo-interstitital nephritis. 

PMID- 24029266
TI  - Ureterocele containing a stone in a duplex system.
AB  - The formation of calcified stone in the ureterocele, a frequent event in adults,
      is very uncommon in a pediatric age. We present a case of a ureterocele
      containing a calcified stone in an 8-year-old girl. The diagnosis was made with
      radiological investigations (intravenous pyelogram, ultrasonography and,
      eventually, voiding cystourethrogram). Meatostomy and calculus extraction, or
      open surgery in more complicated cases, are the treatments of choice. 

PMID- 24029267
TI  - Primary renal carcinoid tumor.
AB  - Primary renal carcinoid tumor is extremely rare and, therefore, its pathogenesis
      and prognosis is not well known. We report a primary renal carcinoid in a 26-year
      old man treated by radical nephrectomy. 

PMID- 24029268
TI  - Extragenitourinary retroperitoneal primary hydatid cyst: a rare cause of
      bilateral lower ureteric obstruction and unilateral limb edema.
AB  - Hydatid cyst is an endemic disease in our country. Most commonly, it occurs in
      the liver and lungs. Bilateral hydroureteronephrosis is one of the rare
      presentations of hydatid disease. Herein, we are reporting an unusual case of
      hydatid disease where the primary mode of presentation was external iliac vein
      compression with chronic renal failure because of bilateral ureteric involvement.
      The patient was treated with bilateral double-J stenting to improve the renal
      function and operated later for removal of hydatid cyst under albendazole drug
      treatment. 

PMID- 24029269
TI  - Therapeutic effect of oral nicotinamide on refractory uremic pruritus: a
      randomized, double-blind study.
AB  - To determine the efficacy of oral nicotinamide with placebo to ameliorate uremic
      pruritus (UP), we conducted a prospective, randomized, double-blind, 4-week study
      in 50 chronic kidney disease patients with refractory UP. The patients were
      randomly allocated to nicotinamide tablet 500 mg twice/day or placebo. All anti
      pruritic agents were discontinued at least two weeks before the study. All the
      patients completed the period of the study and their severity of pruritus was
      evaluated before the start of the study and at the end of each week for four
      weeks by using a traditional Visual Analogue Scale and a modified questionnaire
      method (pruritus score). The average pruritus score before administration of oral
      nicotinamide in the study group and that in the placebo group was 2.96 +/- 0.45
      and 2.72 +/- 0.37, respectively. In the nicotinamide group, the average score of
      pruritus gradually reduced to 1.29 +/- 1.08 and in the placebo group it gradually
      decreased to 1.52 +/- 1.61 at the end of the fourth week. There was no
      significant difference between the reductions of pruritus in both groups, but the
      interaction effect using a linear mixed model was significant between drug and
      time (P <0.026). We conclude that increasing the time of application of
      nicotinamide sodium to more than four weeks may be more effective than placebo in
      reducing itching in uremic patients. 

PMID- 24029270
TI  - Finding new HLA-C alleles is useful for the success of bone marrow
      transplantation.

PMID- 24029271
TI  - Mycobacterium fortuitum peritonitis in a patient receiving continuous ambulatory
      peritoneal dialysis.

PMID- 24029272
TI  - Depressive disorders in Moroccan chronic hemodialysis patients.

PMID- 24029273
TI  - The routine use of urine cytology in initial assessment in a one stop hematuria
      clinic: the controversy continues, but can it be resolved?

PMID- 24029274
TI  - Earthquake: post-crisis renal failure.

PMID- 24029275
TI  - Primary infantile hyperoxaluria: a rare cause of acute renal failure.

PMID- 24029276
TI  - Solubility of melamine crystal in different pH conditions: clinical implication
      for management of melamine intoxication.

PMID- 24029277
TI  - Comparison of urinary citrate excretion between patients with nephrolithiasis and
      healthy volunteers.

PMID- 24029278
TI  - Prevalence of renal disease in Nigerian children infected with the human
      immunodeficiency virus and on highly active anti-retroviral therapy.

PMID- 24029279
TI  - Metanephric adenoma: a case report and review of the literature.

PMID- 24029280
TI  - Pediatric versus adult kidney transplantation activity in Arab countries.
AB  - The objective of this study was to evaluate the current activity of pediatric
      versus adult kidney transplantation activity in the Arab world. A questionnaire
      was mailed to all kidney transplant centers in Arab countries to collect data on
      the kidney transplant activity in a recent single year. Three thousand three
      hundred and nine kidney transplants were performed in one year, with a transplant
      rate of 9.5 per million populations (PMP); 298 were performed for children with a
      pediatric kidney transplant (PKT) rate of 0.87 PMP, which is much lower than that
      of developed countries where it mostly ranges from 5 to 10. The pediatric share
      of all transplants is 9%, which is twice as high as that of European children.
      Kidney transplant programs in most Arab countries rely exclusively on living
      donors as there is a severe shortage of deceased donors. 93.5% of all
      transplants, combined adult and pediatric, were from living donors. Deceased
      transplant activity in Arab countries accounts for 14-31% of all transplants in
      the three countries with deceased donor programs. Of the 212 adult and pediatric
      transplants that were performed from deceased donors in eight countries, only 29
      cases were for pediatric recipients. Deceased PKT is available in the Kingdom of
      Saudi Arabia (KSA), Tunisia and Kuwait. Surprisingly, the PKT share was not
      better in the countries with higher overall kidney transplant rate and or in
      those where deceased transplant was available. PKT is still inactive in most Arab
      countries and mostly relies on living donors. The lack of well-developed deceased
      donor programs is the main issue to be addressed. 

PMID- 24029281
TI  - Allograft biopsy in kidney transplant recipients in the medical city of Baghdad.
AB  - To determine the safety and efficacy of the practice of renal allograft biopsy
      and verify its impact on the management of kidney transplant patients presenting
      with graft dysfunction, we studied 50 renal allograft biopsies of 47 adult
      patients (38% males, mean age 32.4 +/- 11 years) performed in the medical city
      complex from November 2008 to April 2011. All the biopsies were performed with a
      guidance of ultrasound. The procedure, complications, histological diagnoses and
      impact of the biopsy data on patients' management were recorded. Thirty percent
      of the biopsies were performed in the first 12 months post-transplantation and
      24% were performed after the 60 th month. Adequate biopsy was achieved in 76% of
      the patients, with a 96% safety rate. Acute rejection was diagnosed in 38% of the
      biopsies and chronic allograft nephropathy in 38%, and they were the most common
      histological patterns in the study. The results of allograft biopsies positively
      impacted the management strategy in all study groups. Renal allograft biopsy was
      a useful and a relatively safe tool for the diagnosis of acute and chronic graft
      dysfunction in our experience. 

PMID- 24029282
TI  - Barriers to kidney transplantation among adult Sudanese patients on maintenance
      hemodialysis in dialysis units in Khartoum State.
AB  - Kidney transplantation remains the preferred modality of treatment for patients
      with end-stage renal disease. In Sudan, kidney transplantation accounted for 28%
      of the total provided renal replacement therapies. A cross-sectional, hospital
      based study was conducted in hemodialysis (HD) units in Khartoum State during the
      period from September 2010 to January 2011. It aimed to determine the main
      reasons for the currently low renal transplantation rate. Data were obtained by
      direct interviewing using a specifically pre-coded and pre-tested questionnaire
      following a pilot study. A total of 462 adult HD patients were randomly selected
      from the various HD units in Khartoum State; these patients accounted for 16.9%
      of the total HD population in Khartoum State. The mean age of the study patients
      was 48.5 +/- 23.6 years and 312 (67.5%) were males. Upon interviewing, only 316
      patients (68.4%) said that they had been counseled for kidney transplantation.
      One hundred and twenty-two patients (26.4%) were on the active transplant list;
      of these, 50% preferred to have their kidney transplantation performed abroad,
      mostly due to the availability of commercial transplantation and/or a presumed
      better outcome. The low renal transplantation rate was due to financial
      constraints in 112 patients (24.2%), lack of medical fitness in 97 patients (21%)
      and absence of a suitable kidney donor in 92 patients (20%), while 56 patients
      (12%) were still having misperceptions regarding transplantation and preferred to
      continue on dialysis. To improve the kidney transplantation rate in Khartoum
      State, the Sudan program for organ transplantation is expected to take more
      initiatives to promote and improve the outcome of kidney transplants inside the
      country and, accordingly, regain the patients' confidence on the health system. 

PMID- 24029283
TI  - Patterns of childhood nephrotic syndrome in Aljouf region, Saudi Arabia.
AB  - To determine the patterns in children with nephrotic syndrome (NS) in our region,
      we retrospectively studied 25 nephrotic patients evaluated and followed-up in the
      hospitals of the Aljouf region in Saudi Arabia. The male to female ratio was 2:1.
      The incidence of idiopathic NS was two to six cases per 100,000 children/year,
      while the prevalence was 12 cases per 100,000 children. Five patients presented
      with hypertension, seven (28%) with respiratory tract infection, three (12%) with
      tender abdomen, two (8%) with gross hematuria, one (4%) with thrombosis of renal
      veins with seizure and shock and the remaining seven presented to the hospital
      without complications. Twenty-three (92%) patients were sensitive to the first
      steroid course and two (8%) patients were steroid resistant, and both of them
      proved to have focal segmental glomerulosclerosis (FSGS) on biopsy. Of those who
      responded, six (24%) patients remained in remission, while 17 (68%) patients
      became steroid dependant. Of those who were diagnosed as steroid dependent, three
      patients were biopsied and one of them was diagnosed as FSGS, while the remaining
      two had minimal change glomerulonephritis. Regarding steroid-dependent patient
      relapses, seven (41%) patients showed infrequent relapses and ten (59%) patients
      had frequent relapses. We conclude that the patterns of NS and the response to
      treatment observed in this study did not differ significantly from studies from
      other places in the world. 

PMID- 24029284
TI  - Idiopathic urolithiasis in Tunisian children: a report of 134 cases.
AB  - We evaluated the metabolic and the nutritional aspects of 134 urolithiasis
      children in order to outline the characteristics of idiopathic urolithiasis in
      children. This prospective study group of 134 children (56 females, 78 males)
      with renal calculi was evaluated. The age range of the patients was six months to
      16 years. A dietary survey was performed on every child. All patients were
      investigated with respect to stone localization and serum and urine risk factors.
      Statistical analysis of data was carried out using software SPSS 11.0 for
      Windows. Hypercalciuria was the most common risk factor detected in this group
      (28.3%). A decrease of water intake was noted in all age groups, especially in
      the rural area (549.6 mL/day vs. 1150.6 mL/day), and there was an increase in
      animal protein intake in 17 cases (mean: 1.9 g/kg). In addition, increased intake
      of starchy foods and food with high oxalate content (sorgum) were detected in the
      ten to 16 years age group (51%) of our study. Calcium oxalate monohydrate
      represents the principal component of idiopathic stone (58.2%), which is more
      frequent in children (68%) than in infants (51.7%) (P <0.02). The major etiology
      of idiopathic urolithiasis highlights the influence of dietary habit in stone
      formers in our country. The increased occurrence of calcium oxalate stones in
      school age children confirms the change in the etiology of urolithiasis according
      to age. 

PMID- 24029285
TI  - Characteristics of atheromatous renovascular disease in Dubai: a single-center
      experience.
AB  - To determine the characteristics of atherosclerotic renal artery stenosis (ARAS)
      in a cohort of patients who attended the Nephrology Department of NMC Specialty
      Hospital in Dubai from 2006 through 2010, including their clinical and
      investigational features and their response to various remedial modalities, we
      studied 20 patients with a diagnosis of ARAS based on magnetic resonance
      angiography. Three (15%) patients developed acute renal failure (ARF) after the
      initiation of angiotensin converting enzyme inhibitors or angiotensin II receptor
      blockers and 13 (65%) patients presented with chronic kidney disease (CKD) of
      either ischemic nephropathy or nephroangiosclerosis etiology. Four (20%) patients
      presented with resistant arterial hypertension (RAH). Plasma renin activity was
      elevated in all the patients. Fifteen (75%) patients were diabetics. We conclude
      that CKD was the main presentation of ARAS followed by RAH and ARF in our study.
      Diabetes Mellitus was the main risk factor for ARAS found in our study. 

PMID- 24029286
TI  - Epidemiological patterns of chronic kidney disease in black African elders: a
      retrospective study in West Africa.
AB  - Chronic kidney disease (CKD) is frequently described in elders. This study
      describes the epidemiological patterns of patients >=60 years old admitted in our
      department during one year. The prevalence of CKD was 10.8% (60/552). The mean
      age of the patients was 70.5 years (60-84 years) and the sex ratio (male:female)
      was 1.08. The mean serum creatinine level was 7.10 mg/dL (1.31-25.0 mg/dL) and
      more than two-third of the patients presented CKD stage 4-5. Causes of CKD were
      dominated by hypertension (30%) and diabetes (25%). Prevalence of inpatients aged
      60-69 years old was higher than in those >=80 years old but lower than that in
      patients aged 70-79 years. At admission, 83.3% of the patients were hypertensive,
      75% were anemic and 13% presented proteinuria. The main co-morbidities associated
      with CKD were neoplasms (17% of cases), chronic heart disease (15% of cases) and
      pneumonia (15% of cases). Furosemide was prescribed in 55% of the patients,
      calcium channel blockers in 23% of the patients and ACE inhibitors in 20% of the
      patients. Renal replacement therapy was not performed for any patient. Evolution
      was favorable in the majority of patients (77%), but 23% died mainly because of
      uremia and infections. 

PMID- 24029287
TI  - Tumor-penetrating peptide functionalization enhances the anti-glioblastoma effect
      of doxorubicin liposomes.
AB  - The targeted therapeutic effect of nano drug delivery system for glioblastoma has
      been hampered by the weak enhanced permeability and retention (EPR) effect of
      glioblastoma and the low delivering efficiency of NDDS in glioblastoma tissue. In
      this study, a tumor-penetrating peptide (RGERPPR), the specific ligand of
      neuropilin-1 overexpressed on glioblastoma and endothelial cells, was used as a
      targeting moiety to enhance the anti-glioblastoma effect of doxorubicin
      liposomes. Firstly, RGERPPR-PEG-DSPE was synthesized and used to prepare the
      RGERPPR peptide-functionalized liposomes (RGE-LS), which showed vesicle sizes of
      around 90 nm and narrow size distributions. The cellular uptake and in vivo near
      infrared fluorescence imaging test displayed that RGE-LS exhibited increased
      uptake by glioblastoma cells and intracranial glioblastoma tissues. The
      cytotoxicity assay and anti-glioblastoma study proved that RGERPPR
      functionalization significantly enhanced the in vitro inhibitory effect of
      doxorubicin liposomes on glioblastoma cells and prolonged the median survival
      time of nude mice bearing intracranial glioblastoma. Finally, the
      immunofluorescence analysis evidenced that RGE-LS were able to penetrate through
      tumor vessels and stroma and deep into the whole tumor tissue. The results
      indicated that tumor-penetrating peptide functionalization is an effective
      strategy for enhancing the anti-glioblastoma effect of doxorubicin liposomes.

PMID- 24029288
TI  - Environmental estrogens in an urban aquatic ecosystem: II. Biological effects.
AB  - Urban aquatic ecosystems are often overlooked in toxicological studies even
      though they serve many ecosystem functions and sustain fish populations despite
      large-scale habitat alterations. However, urban fish populations are likely
      exposed to a broad range of stressors, including environmental estrogens (EEs)
      that may affect anatomy, physiology and reproduction of exposed fish. Although
      significant progress has been made in establishing ecological consequences of EE
      exposure, these studies have focused largely on hydrologically simple systems
      that lack the complexity of urban aquatic environments. Therefore, the objective
      of this study was to assess the occurrence and biological effects of EEs across a
      large urbanized aquatic ecosystem. A multi-pronged study design was employed
      relying on quantitative determination of select EEs by liquid chromatography
      tandem mass spectrometry and repeated biological monitoring of wild-caught and
      caged fish for indications of endocrine disruption. Over three years, EEs were
      measured in aqueous samples (n=42 samples) and biological effects assessed in
      >1200 male fish across the 2000km(2) aquatic ecosystems of the Greater
      Metropolitan Area of Chicago, IL. Our study demonstrated that in addition to
      water reclamation plant (WRP) effluents, non-WRP sources contribute significant
      EE loads to the aquatic ecosystem. While resident and caged male fish responded
      with the induction of the egg-yolk protein vitellogenin, an indicator of EE
      exposure, neither resident nor caged sunfish exhibited prevalent
      histopathological changes to their reproductive organs (i.e., intersex) that have
      been reported in other studies. Vitellogenin induction was greater in spring than
      the fall and was not correlated with body condition factor, gonadosomatic index
      or hepatosomatic index. Exposure effects were not correlated with sites
      downstream of treated effluent discharge further affirming the complexity of
      sources and effects of EEs in urban aquatic ecosystems. 

PMID- 24029289
TI  - [Thrombosis risk during pregnancy after history of cerebral venous thrombosis].
AB  - INTRODUCTION: Few data have been published about the prognosis of a pregnancy
      following an episode of venous cerebral thrombosis (CVT), and far less about
      preventive strategy. METHODS: This is a retrospective study of a case series of
      11 pregnancies in six women who had previously presented a CVT. RESULTS: The
      first pregnancies after CVT occurred on average 58 months later. Prevention with
      aspirin or heparin was administered in ten cases during pregnancy, and in all the
      cases with heparin in postpartum. No recurrence of CVT was observed. A minor
      pulmonary embolism was diagnosed in postpartum in one case. CONCLUSION: Prognosis
      of a pregnancy after a CVT seems to be favourable if a sufficient delay after CVT
      is respected. Although no results of controlled trials are available, prophylaxis
      with heparin is probably reasonable as benefit seems higher than risks and is
      strongly advised during the postpartum period.

PMID- 24029290
TI  - [How to read a meta-analysis?].
AB  - Meta-analysis is aimed at assessing an exhaustive, unbiased, reproducible,
      quantified and accurate synthesis of a research problem. It is sustained by a
      systematic review of the literature and has statistical particularities. Sources
      of error and bias are numerous. In this paper, we describe them following the
      methodology steps of a well-conducted meta-analysis. Causes of divergent
      conclusions of meta-analyses are described and illustrated with the example of
      cancer risk assessment in TNF inhibitor-treated rheumatoid arthritis patients.
      Eventually, this article provides key-points to help readers to detect sources of
      error and bias in meta-analyses. 

PMID- 24029291
TI  - Effect of inhaled tacrolimus on ischemia reperfusion injury in rat lung
      transplant model.
AB  - OBJECTIVE: Systemic tacrolimus therapy has been shown to protect against lung
      ischemia-reperfusion injury in animal models. We sought to investigate on a
      functional and cellular level if inhaled nanoparticle tacrolimus administered to
      the donor lung before procurement could similarly attenuate ischemia-reperfusion
      injury after lung transplant. METHODS: An isogenic orthotopic rat model of single
      left lung transplant was used. Donor animals were pretreated with inhaled
      tacrolimus (treatment group) or inhaled lactose (controls) before lung
      procurement. Lung grafts were subjected to 3 hours of cold ischemia followed by 4
      hours of reperfusion after graft implantation. Recipient animal arterial blood
      gas measurement and isograft wet to dry weight ratios were obtained. Macrophage,
      neutrophil, and T-cell accumulation and activation in lung isografts, including
      gammadelta T-cell, T-helper, and cytotoxic T-cell subtypes were analyzed by flow
      cytometry. Tacrolimus levels were measured in the lung isograft using liquid
      chromatography/mass spectrometry. Isograft cytokine levels were measured with
      commercial enzyme-linked immunosorbent assay and microbead array kits. RESULTS:
      Oxygenation in treatment group animals was significantly higher than in controls.
      The presence of macrophages, neutrophils, and all T-cell subtypes in the
      isografts as well as isograft levels of inflammatory cytokines were all less in
      the treatment group versus controls, although no single variable achieved
      statistical significance. CONCLUSIONS: Inhaled nanoparticle tacrolimus treatment
      of lung donors is associated with an attenuation of ischemia-reperfusion injury
      on a functional and cellular level in lung transplant.

PMID- 24029293
TI  - Development of a life-threatening mediastinal hematoma from a ruptured bronchial
      artery aneurysm.

PMID- 24029294
TI  - Predictors of late aortic events after Stanford type B acute aortic dissection.
AB  - OBJECTIVE: Patients with Stanford type B acute aortic dissection usually receive
      medical treatment during the acute phase. The present study aimed to elucidate
      the factors predicting late aortic events in patients treated conservatively for
      acute type B dissections. METHODS: From March 1991 to March 2011, 117 patients
      were enrolled in the present study, with a mean follow-up period of 5.1 +/- 4.1
      years. The patients were divided into 4 groups according to their false lumen
      status at onset: group F, fully open (n = 26, 22.2%); group P, partially
      thrombosed (n = 23, 19.6%); group U, ulcer-like projections (n = 22, 18.9%); and
      group T, completely thrombosed (n = 46, 39.3%). RESULTS: Long-term survival did
      not significantly differ among the groups. The Kaplan-Meier event-free rate curve
      showed that aortic events occurred less frequently in group T than in the other 3
      groups; the 5-year event-free rate was 65.4%, 58.8%, 36.1%, and 95.7% for groups
      F, P, U, and T, respectively. Cox regression analysis showed that the presence of
      ulcer-like projections (P = .016) and a maximum aortic diameter of >= 40 mm (P =
      .003) were predictors of late aortic events. CONCLUSIONS: When patients have a
      maximum aortic diameter of >=40 mm or ulcer-like projections at onset, early
      surgical intervention should be considered to prevent positive remodeling of the
      aorta.

PMID- 24029295
TI  - Direct access compared with referred physical therapy episodes of care: a
      systematic review.
AB  - BACKGROUND: Evidence suggests that physical therapy through direct access may
      help decrease costs and improve patient outcomes compared with physical therapy
      by physician referral. PURPOSE: The purpose of this study was to conduct a
      systematic review of the literature on patients with musculoskeletal injuries and
      compare health care costs and patient outcomes in episodes of physical therapy by
      direct access compared with referred physical therapy. DATA SOURCES: Ovid
      MEDLINE, CINAHL (EBSCO), Web of Science, and PEDro were searched using terms
      related to physical therapy and direct access. Included articles were hand
      searched for additional references. STUDY SELECTION: Included studies compared
      data from physical therapy by direct access with physical therapy by physician
      referral, studying cost, outcomes, or harm. The studies were appraised using the
      Centre for Evidence-Based Medicine (CEBM) levels of evidence criteria and
      assigned a methodological score. DATA EXTRACTION: Of the 1,501 articles that were
      screened, 8 articles at levels 3 to 4 on the CEBM scale were included. There were
      statistically significant and clinically meaningful findings across studies that
      satisfaction and outcomes were superior, and numbers of physical therapy visits,
      imaging ordered, medications prescribed, and additional non-physical therapy
      appointments were less in cohorts receiving physical therapy by direct access
      compared with referred episodes of care. There was no evidence for harm. DATA
      SYNTHESIS: There is evidence across level 3 and 4 studies (grade B to C CEBM
      level of recommendation) that physical therapy by direct access compared with
      referred episodes of care is associated with improved patient outcomes and
      decreased costs. LIMITATIONS: Primary limitations were lack of group
      randomization, potential for selection bias, and limited generalizability.
      CONCLUSIONS: Physical therapy by way of direct access may contain health care
      costs and promote high-quality health care. Third-party payers should consider
      paying for physical therapy by direct access to decrease health care costs and
      incentivize optimal patient outcomes.

PMID- 24029296
TI  - Reliability of a progressive maximal cycle ergometer test to assess peak oxygen
      uptake in children with mild to moderate cerebral palsy.
AB  - BACKGROUND: Rehabilitation research in children with cerebral palsy (CP) is
      increasingly addressing cardiorespiratory fitness testing. However, evidence on
      the reliability of peak oxygen uptake (Vo2peak) measurements, considered the best
      indicator of aerobic fitness, is not available in this population. OBJECTIVE: The
      objective of this study was to establish the reliability of a progressive maximal
      cycle ergometer test when assessing Vo2peak in children with mild to moderate CP.
      DESIGN: Repeated measures were used to assess test-retest reliability. METHODS:
      Eligible participants were ambulant, 6 to 14 years of age, and classified as
      level I, II, or III according to the Gross Motor Function Classification System
      (GMFCS). Two progressive maximal cycle ergometer tests were conducted (separated
      by 3 weeks), with the workload increasing every minute in steps of 3 to 11 W,
      dependent on height and GMFCS level. Reliability was determined by means of the
      intraclass correlation coefficient (ICC [2,1]) and smallest detectable change
      (SDC). RESULTS: Twenty-one children participated (GMFCS I: n=4; GMFCS II: n=12;
      and GMFCS III: n=5). Sixteen of them (9 boys, 7 girls; GMFCS I: n=3; GMFCS II:
      n=11; and GMFCS III: n=2) performed 2 successful tests, separated by 9.5 days on
      average. Reliability for Vo2peak was excellent (ICC=.94, 95% confidence
      interval=.83-.98). The SDC was 5.72 mL/kg/min, reflecting 14.6% of the mean.
      LIMITATIONS: The small sample size did not allow separate analysis of reliability
      per GMFCS level. CONCLUSIONS: In children with CP of GMFCS levels I and II, a
      progressive maximal cycle ergometer test to assess Vo2peak is reliable and has
      the potential to detect change in cardiorespiratory fitness over time. Further
      study is needed to establish the reliability of Vo2peak in children of GMFCS
      level III.

PMID- 24029297
TI  - Development and validation of the computer-administered animated activity
      questionnaire to measure physical functioning of patients with hip or knee
      osteoarthritis.
AB  - BACKGROUND: Physical functioning of patients with hip or knee osteoarthritis is
      measured by self-report questionnaires and performance-based tests. However,
      performance-based tests often are not feasible. OBJECTIVE: The aim of this study
      was to develop a computer-administered questionnaire (ie, the Animated Activity
      Questionnaire [AAQ]) to measure physical functioning in patients with hip or knee
      OA. By showing animations of activities, the influence of the patient's own
      reference frame is minimized. The AAQ measures the same aspects of physical
      functioning as performance-based tests do. DESIGN: This was a development and
      preliminary validation (cross-sectional) study. METHODS: A pilot version of the
      AAQ was developed using motion capture to analyze the movement of a person
      performing 7 daily activities. Different animations of the same activity were
      made with 2 to 5 levels of difficulty. For each activity, participants were asked
      to choose one animation that best corresponds to their own way of performing the
      activity. A preliminary validation study was performed to compare the AAQ with
      validated self-report questionnaires (Knee Injury and Osteoarthritis Outcome
      Score, Hip Disability and Osteoarthritis Outcome Score, and questionnaires on
      walking, stair climbing, and rising and sitting down) and performance-based tests
      (walking, Timed "Up & Go" Test, Timed Stair Test) in 33 patients with hip or knee
      osteoarthritis. RESULTS: As expected, the AAQ showed a correlation above .70
      (.79, 95% confidence interval=.61-.89) with the total score of the performance
      based tests. On the subscore level, the results were partly as expected. Fifty
      eight percent of the participants preferred the AAQ over self-report
      questionnaires and performance-based tests. LIMITATIONS: The findings need to be
      replicated in larger samples of patients because the sample size of the study was
      rather small. CONCLUSION: The AAQ might be a good alternative for measuring
      physical functioning of patients with hip or knee osteoarthritis. The AAQ can
      easily be adapted for use in other patient populations. However, further
      development and validation are needed.

PMID- 24029298
TI  - Exposure to therapy of older patients with trauma and factors that influence
      provision of therapy.
AB  - BACKGROUND: Rehabilitation as soon as possible after trauma decreases sedentary
      behavior, deconditioning, length of stay, and risk of rehospitalization.
      OBJECTIVE: The study objectives were to describe exposure of older patients with
      trauma to rehabilitation and to explore factors associated with the number and
      initiation of therapy sessions. DESIGN: This was a retrospective study of data
      from electronic medical records. METHODS: Randomly selected older patients with
      trauma were described with regard to demographics, trauma diagnoses,
      comorbidities, preadmission function, and exposure to therapy. Regression
      analyses explored factors associated with number of therapy sessions and days
      until therapy was ordered and completed. RESULTS: Records for 137 patients were
      randomly selected from records for 1,387 eligible patients who had trauma and
      were admitted over a 2-year period to a level I trauma center. The 137 patients
      received 303 therapy sessions. The sample included 63 men (46%) and 74 women
      (54%) who were 78 (SD=10) years of age; most patients were white (n=115 [84%]).
      All patients had orders for therapy, although 3 patients (2%) were never seen. An
      increase in comorbidities was associated with an increase in therapy sessions, a
      decrease in the number of days until an order was written, but an increase in the
      number of days from admission to evaluation. Injury severity was associated with
      a decrease in the number of days from admission to an order being written. A
      postponed or canceled therapy session was associated with increases in the number
      of days from admission to evaluation and in the number of days from an order
      being written to evaluation. LIMITATIONS: This study was a retrospective review
      of a small sample with subjective measures and several dichotomous variables.
      CONCLUSIONS: Increased injury severity, increased numbers of comorbidities, and
      postponed or canceled therapy sessions were associated with decreased time from
      admission to therapy orders, increased time from admission and orders to
      evaluation, and increased number of therapy sessions.

PMID- 24029300
TI  - Physical therapist-delivered cognitive-behavioral therapy: a qualitative study of
      physical therapists' perceptions and experiences.
AB  - BACKGROUND: The importance of the biopsychosocial model in assessment and
      management of chronic musculoskeletal conditions is recognized. Physical
      therapists have been encouraged to develop psychologically informed practice.
      Little is known about the process of physical therapists' learning and delivering
      of psychological interventions within the practice context. OBJECTIVE: The aim of
      this study was to investigate physical therapists' experiences and perspectives
      of a cognitive-behavioral-informed training and intervention process as part of a
      randomized controlled trial (RCT) involving adults with painful knee
      osteoarthritis. DESIGN: A qualitative design was used. Participants were physical
      therapists trained to deliver pain coping skills training (PCST). METHODS: Eight
      physical therapists trained to deliver PCST were interviewed by telephone at 4
      time points during the 12-month RCT period. Interviews were audiorecorded,
      transcribed verbatim into computer-readable files, and analyzed using Framework
      Analysis. RESULTS: Thematic categories identified were: training, experience
      delivering PCST, impact on general clinical practice, and perspectives on PCST
      and physical therapist practice. Physical therapists reported positive
      experiences with PCST and program delivery. They thought that their participation
      in the RCT had enhanced their general practice. Although some components of the
      PCST program were familiar, the therapists found delivering the program was quite
      different from regular practice. Physical therapists believed the PCST program, a
      3- to 4-day workshop followed by formal mentoring and performance feedback from a
      psychologist for 3 to 6 months and during the RCT, was critical to their ability
      to effectively deliver the PCST intervention. They identified a number of
      challenges in delivering PCST in their normal practice. CONCLUSION: Physical
      therapists can be trained to confidently deliver a PCST program. The physical
      therapists in this study believed that training enhanced their clinical practice.
      Comprehensive training and mentoring by psychologists was crucial to ensure
      treatment fidelity.

PMID- 24029299
TI  - Adherence to accelerometry measurement of community ambulation poststroke.
AB  - BACKGROUND: The step activity monitor (SAM) quantifies steps taken in the home
      and community by patient populations. Although the SAM has been used to study
      individuals after stroke, adherence to the use of SAMs has not been addressed.
      Participants' adherence to wearing the monitor is critical for obtaining accurate
      assessments. OBJECTIVE: The purpose of this study was to determine the rate of
      and predictors for inferred adherence to the use of the SAM after stroke. DESIGN:
      A cross-sectional design was used. METHODS: Community-dwelling individuals
      (n=408) 2 months after stroke with moderate-to-severe gait impairment (gait speed
      of <=0.8 m/s) were studied. Step activity was assessed for 2 days with the SAM.
      Inferred adherence was established in 3 periods: 6:00 am to 12:00 pm, 12:01 pm to
      6:00 pm, and 6:01 pm to 12:00 am. Adherence was defined as activity recorded in
      all 3 periods. The percentage of participant adherence for the first day, second
      day, both days, and either day was calculated. Demographic and clinical
      characteristics of adherers and nonadherers were compared. Independent adherence
      predictors were identified by means of stepwise logistic regression. RESULTS:
      Inferred adherence rates for the first day, second day, both days, and either day
      were 68%, 61%, 53%, and 76%, respectively. Upper and lower extremity impairment,
      balance control, and endurance were significantly different between adherers and
      nonadherers. On the other hand, older age, greater balance self-efficacy, and
      better walking endurance were significant predictors of adherence. LIMITATIONS:
      Participants were individuals with subacute stroke. Therefore, the findings of
      this study may not be generalized to individuals during the acute and chronic
      phases of stroke recovery. CONCLUSIONS: Strategies to improve adherence are
      needed when collecting data for more than 1 day and in samples with younger
      individuals and those with low levels of balance self-efficacy and walking
      endurance.

PMID- 24029301
TI  - Relative and absolute reliability of a vertical numerical pain rating scale
      supplemented with a faces pain scale after stroke.
AB  - BACKGROUND: Pain is a serious adverse complication after stroke. The combination
      of a vertical numerical pain rating scale (NPRS) and a faces pain scale (FPS) has
      been advocated to measure pain after stroke. OBJECTIVE: This study was conducted
      to investigate whether an NPRS supplemented with an FPS (NPRS-FPS) would show
      good test-retest reliability in people with stroke. The relative and absolute
      reliability of the NPRS-FPS were examined. DESIGN: A test-retest design was used
      for this study. METHODS: Fifty people (>3 months after stroke) participating in
      an outpatient occupational therapy program were recruited through medical centers
      to rate current pain intensity twice, at a 1-week interval, with the NPRS-FPS (on
      a scale from 0 to 10). The relative reliability of the NPRS-FPS was analyzed with
      the intraclass correlation coefficient for determining the degree of consistency
      and agreement between 2 measures. The standard error of measurement, the smallest
      real difference, and Bland-Altman limits of agreement were the absolute
      reliability indexes used to quantify measurement errors and determine systematic
      biases of repeated measurements. RESULTS: The relative reliability of the NPRS
      FPS was substantial (intraclass correlation coefficient=.82). The standard error
      of measurement and the smallest real difference at the 90% confidence interval of
      the NPRS-FPS were 0.81 and 1.87, respectively. The Bland-Altman analyses revealed
      no significant systematic bias between repeated measurements for the NPRS-FPS.
      The range of the limits of agreement for the NPRS-FPS was narrow (-2.50 to 1.90),
      indicating a high level of stability and little variation over time. LIMITATIONS:
      The pain intensity of the participants ranged from no pain to a moderate level of
      pain. CONCLUSIONS: These findings suggest that the NPRS-FPS is a reliable measure
      of pain in people with stroke, with good relative and absolute reliability.

PMID- 24029302
TI  - Physical activity and sedentary behaviors in people with stroke living in the
      community: a systematic review.
AB  - BACKGROUND: Regular physical activity is vital for cardiovascular health. Time
      spent in sedentary behaviors (eg, sitting, lying down) also is an independent
      risk factor for cardiovascular disease. The pattern in which sedentary time is
      accumulated is important-with prolonged periods of sitting time being
      particularly deleterious. People with stroke are at high risk for cardiovascular
      disease, including recurrent stroke. PURPOSE: This systematic review aimed to
      update current knowledge of physical activity and sedentary behaviors among
      people with stroke living in the community. A secondary aim was to investigate
      factors associated with physical activity levels. DATA SOURCES: The data sources
      used were MEDLINE, Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), Allied and Complimentary Medicine Database (AMED), EMBASE, and the
      Cochrane Library. STUDY SELECTION: Studies involving people with stroke living in
      the community and utilizing objective measures of physical activity or sedentary
      behaviors were included. DATA EXTRACTION: Data were extracted by one reviewer and
      checked for accuracy by a second person. DATA SYNTHESIS: Twenty-six studies,
      involving 983 participants, were included. The most common measure of activity
      was steps per day (22 studies), which was consistently reported as less than half
      of age-matched normative values. Only 4 studies reported on sedentary time
      specifically. No studies described the pattern by which sedentary behaviors were
      accumulated across the day. Walking ability, balance, and degree of physical
      fitness were positively associated with higher levels of physical activity.
      LIMITATIONS: This review included only studies of people living in the community
      after stroke who were able to walk, and the majority of included participants
      were aged between 65 and 75 years of age. CONCLUSIONS: Little is known about the
      time people with stroke spend being sedentary each day or the pattern in which
      sedentary time is accumulated. Studies using objective, reliable, and valid
      measures of sedentary time are needed to further investigate the effects of
      sedentary time on the health of people with stroke.

PMID- 24029303
TI  - Secondary prevention of new vascular events with lifestyle intervention in
      patients with noncardioembolic mild ischemic stroke: a single-center randomized
      controlled trial.
AB  - BACKGROUND: Lifestyle modification is associated with a substantially decreased
      risk of cardiovascular events. However, the role of lifestyle intervention for
      secondary prevention in patients with noncardioembolic ischemic stroke is
      inadequately defined. We assessed the hypothesis that lifestyle intervention can
      reduce the onset of new vascular events in patients with noncardioembolic mild
      ischemic stroke. METHODS: We conducted an observer-blind randomized controlled
      trial that enrolled 70 patients (48 men, mean age 63.5 years) with acute
      noncardioembolic mild ischemic stroke. The patients were allocated in equal
      numbers to a lifestyle intervention group or a control group. We performed
      lifestyle interventions, which comprised exercise training, salt restriction and
      nutrition advice for 24 weeks. Then all patients were prospectively followed up
      for occurrence of the primary endpoints, including hospitalization due to stroke
      recurrence and the onset of other vascular events. We also evaluated systolic
      blood pressure (SBP) at the clinic and at home, low-density lipoprotein
      cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hemoglobin A1c
      (HbA1c) and high-sensitivity C-reactive protein (hs-CRP) to compare the efficacy
      of the lifestyle interventions. RESULTS: This trial was terminated earlier than
      expected because of the prespecified early stopping rule for efficacy. After the
      24-week intervention period, the intervention group showed a significant increase
      in daily physical activity and a significant decrease in salt intake (physical
      activity, p = 0.012; salt intake, p < 0.001), with a significant difference
      between the randomized groups (physical activity, p < 0.001; salt intake, p =
      0.018). Similarly, blood pressure was decreased and the HDL-C levels were
      increased in the intervention group (SBP, p < 0.001; HDL-C, p = 0.018), with
      significant differences between the randomized groups (SBP, p < 0.001; HDL-C, p =
      0.022). In contrast, LDL-C, HbA1c and hs-CRP tended to decrease in the
      intervention group, but this decrease did not achieve significance. After a
      median follow-up period of 2.9 years, 12 patients allocated to the control group
      and 1 patient in the lifestyle intervention group experienced at least 1 vascular
      event. A sequential plans analysis indicated the superiority of the lifestyle
      intervention in interim analysis. Kaplan-Meier survival curves after the log-rank
      test showed a significant prognostic difference between the randomized groups (p
      = 0.005). CONCLUSIONS: Lifestyle intervention with appropriate medication is
      beneficial for reducing the incidence of new vascular events and improving
      vascular risk factors in patients with noncardioembolic mild ischemic stroke.

PMID- 24029304
TI  - A randomized wait-list controlled pilot study of dialectical behaviour therapy
      guided self-help for binge eating disorder.
AB  - This study examined the efficacy of guided self-help based on dialectical
      behaviour therapy (DBTgsh) for binge eating disorder (BED). Individuals (88.3%
      female; mean 42.8 years) were randomized to DBTgsh (n=30) or wait-list (WL;
      n=30). DBTgsh participants received an orientation, DBT manual, and six 20-min
      support calls over 13 weeks. All participants were assessed pre- and post
      treatment using interview and self-report; also, DBTgsh participants were re
      assessed six months post-treatment. At treatment end, DBTgsh participants
      reported significantly fewer past-month binge eating episodes than WL
      participants (6.0 versus 14.4) and significantly greater rates of abstinence from
      binge eating (40.0% versus 3.3%). At six-month follow-up, DBTgsh participants
      reported significantly improved quality of life and reduced ED psychopathology
      compared to baseline scores. In addition, most improvements in the DBTgsh group
      were maintained, although binge eating abstinence rates decreased to 30%. These
      preliminary positive findings indicate that DBTgsh may offer an effective, low
      intensity treatment option for BED.

PMID- 24029305
TI  - Re: Ipsilateral adrenalectomy at the time of radical nephrectomy impacts overall
      survival.

PMID- 24029306
TI  - Re: Long-term oncologic outcomes after radiofrequency ablation for T1 renal cell
      carcinoma.

PMID- 24029307
TI  - Re: Standardized analysis of frequency and severity of complications after robot
      assisted radical cystectomy.

PMID- 24029308
TI  - Re: Transperineal template-guided saturation biopsy using a modified technique:
      outcome of 270 cases requiring repeat prostate biopsy.

PMID- 24029309
TI  - Re: Validation of a cell-cycle progression gene panel to improve risk
      stratification in a contemporary prostatectomy cohort.

PMID- 24029310
TI  - Re: Use of testosterone replacement therapy in the United States and its effect
      on subsequent prostate cancer outcomes.

PMID- 24029311
TI  - Re: Effect of age, tumor risk, and comorbidity on competing risks for survival in
      a U.S. population-based cohort of men with prostate cancer.

PMID- 24029312
TI  - Re: Mortality after radical prostatectomy or external beam radiotherapy for
      localized prostate cancer.

PMID- 24029313
TI  - Re: Very distal apical prostate tumours: identification on multiparametric MRI at
      3 Tesla.

PMID- 24029314
TI  - Re: Validation of the European Society of Urogenital Radiology scoring system for
      prostate cancer diagnosis on multiparametric magnetic resonance imaging in a
      cohort of repeat biopsy patients.

PMID- 24029315
TI  - Re: Tumour characteristics, oncological and functional outcomes in patients aged
      >= 70 years undergoing radical prostatectomy.

PMID- 24029316
TI  - Re: Predictors of immediate continence following robot-assisted radical
      prostatectomy.

PMID- 24029317
TI  - Re: Certificate of need regulations and the diffusion of intensity-modulated
      radiotherapy.

PMID- 24029318
TI  - Re: Prostate cancer screening in men ages 75 and older fell by 8 percentage
      points after Task Force recommendation.

PMID- 24029319
TI  - Re: An alternative treatment regimen of advanced seminoma with carboplatin,
      etoposide, and bleomycin instead of cisplatin-based therapy.

PMID- 24029320
TI  - Re: Decision aids: when 'nudging' patients to make a particular choice is more
      ethical than balanced, nondirective content.

PMID- 24029321
TI  - Re: Nitrofurantoin-induced lung disease and prophylaxis of urinary tract
      infections.

PMID- 24029322
TI  - Re: Genomic diversity and fitness of E. coli strains recovered from the
      intestinal and urinary tracts of women with recurrent urinary tract infection.

PMID- 24029323
TI  - Re: Similarity and divergence of phylogenies, antimicrobial susceptibilities, and
      virulence factor profiles of Escherichia coli isolates causing recurrent urinary
      tract infections that persist or result from reinfection.

PMID- 24029324
TI  - Re: Urinary tract infection in male veterans: treatment patterns and outcomes.

PMID- 24029325
TI  - Re: The role of Oxalobacter formigenes colonization in calcium oxalate stone
      disease.

PMID- 24029326
TI  - Re: Ascorbic acid supplements and kidney stone incidence among men: a prospective
      study.

PMID- 24029329
TI  - Re: The role of interventional radiology in urologic tract trauma.

PMID- 24029330
TI  - Re: Application of Yang-Monti principle in ileal ureter substitution: is it a
      beneficial modification?

PMID- 24029331
TI  - Re: Thirty-day outcomes support implementation of a surgical safety checklist.

PMID- 24029332
TI  - Re: Relationship between occurrence of surgical complications and hospital
      finances.

PMID- 24029333
TI  - Re: Persistence with prescribed antimuscarinic therapy for overactive bladder: a
      UK experience.

PMID- 24029334
TI  - Re: When are urodynamics indicated in patients with stress urinary incontinence?

PMID- 24029335
TI  - Re: Menopausal hormone therapy for the primary prevention of chronic conditions:
      a systematic review to update the U.S. Preventive Services Task Force
      recommendations.

PMID- 24029336
TI  - Re: Effect of physical training on urinary incontinence: a randomized parallel
      group trial in nursing homes.

PMID- 24029337
TI  - Re: Chronic urinary retention in men: how we define it, and how does it affect
      treatment outcome.

PMID- 24029338
TI  - Re: Transurethral laser surgery for benign prostate hyperplasia in octogenarians:
      safety and outcomes.

PMID- 24029339
TI  - Re: Success rates, quality of life, and feasibility of sacral nerve stimulation
      in elderly patients: 1-year follow-up.

PMID- 24029340
TI  - Re: Association between physical activity, lower urinary tract symptoms (LUTS)
      and prostate volume.

PMID- 24029341
TI  - Re: Debilitating lower urinary tract symptoms in the post-renal transplant
      population can be predicted pretransplantation.

PMID- 24029342
TI  - Re: Testosterone replacement therapy and prostate health.

PMID- 24029343
TI  - Re: Quantification of the early risk of death in elderly kidney transplant
      recipients.

PMID- 24029344
TI  - Re: Renal transplantation after ex vivo normothermic perfusion: the first
      clinical study.

PMID- 24029345
TI  - Re: Comparative effectiveness and safety of oral phosphodiesterase type 5
      inhibitors for erectile dysfunction: a systematic review and network meta
      analysis.

PMID- 24029350
TI  - Re: In vitro fertilization and risk of breast and gynecologic cancers: a
      retrospective cohort study within the Israeli Maccabi Healthcare Services.

PMID- 24029351
TI  - Re: Preservation of sexual function with the prostatic urethral lift: a novel
      treatment for lower urinary tract symptoms secondary to benign prostatic
      hyperplasia.

PMID- 24029352
TI  - Re: Smoking and infertility: a committee opinion.

PMID- 24029353
TI  - Re: Vasopressin effectively suppresses male fertility.

PMID- 24029354
TI  - Re: Semen analysis in adolescent cancer patients prior to bone marrow
      transplantation: when is it too late for fertility preservation?

PMID- 24029356
TI  - Re: Quality assessment of economic analyses in pediatric urology.

PMID- 24029357
TI  - Re: Factors that predict the spontaneous passage of ureteric stones in children.

PMID- 24029358
TI  - Re: Predictive power of objectivation of phimosis grade on outcomes of topical
      0.1% betamethasone treatment of phimosis.

PMID- 24029359
TI  - Re: Circumcision policy statement.

PMID- 24029360
TI  - Re: Shrinkage of experimental benign prostatic hyperplasia and reduction of
      prostatic cell volume by a gastrin-releasing peptide antagonist.

PMID- 24029361
TI  - Re: Down-regulation of CatSper1 channel in epididymal spermatozoa contributes to
      the pathogenesis of asthenozoospermia, whereas up-regulation of the Channel by
      Sheng-Jing-San treatment improves the sperm motility of asthenozoospermia in
      rats.

PMID- 24029362
TI  - Re: Downregulation of Ral GTPase-activating protein promotes tumor invasion and
      metastasis of bladder cancer.

PMID- 24029363
TI  - Re: Uromodulin upregulates TRPV5 by impairing caveolin-mediated endocytosis.

PMID- 24029364
TI  - Plasma proANP and SDMA and microRNAs are associated with chronic mitral
      regurgitation in a pig model.
AB  - OBJECTIVE: NON-ISCHEMIC MITRAL REGURGITATION (MR) IS PRIMARILY CAUSED BY
      MYXOMATOUS MITRAL VALVE (MV) DISEASE LEADING TO ADAPTIVE REMODELING, ENLARGEMENT,
      AND DYSFUNCTION OF THE LEFT VENTRICLE. THE AIM OF THIS STUDY WAS TO EXAMINE THE
      REGULATION OF PLASMA MARKERS AND SEVERAL CARDIAC KEY GENES IN A NOVEL PORCINE
      MODEL OF NON-ISCHEMIC MR. METHODS AND RESULTS: Twenty-eight production pigs (Sus
      scrofa) were randomized to experimental MR or sham surgery controls. MR was
      induced by external suture(s) through the posterior MV leaflet and quantified
      using echocardiography. The experimental group was subdivided into mild MR (mMR,
      MR=20-50%, n=10) and moderate/severe MR (sMR, MR >50%, n=6) and compared with
      controls (CON, MR <=10%, n=12). Eight weeks postoperatively, follow-up
      examinations were performed followed by killing. Circulating concentrations of
      pro-atrial natriuretic peptide (proANP), l-arginine, asymmetric dimethylarginine,
      and symmetric dimethylarginine (SDMA) were measured. MV, anterior papillary
      muscle, and left ventricular free wall tissues were collected to quantify mRNA
      expression of eNOS (NOS3), iNOS (NOS2), MMP9, MMP14, ANP (NPPA), BNP (NPPB), and
      TGFB1, 2, and 3 and five microRNAs by quantitative real-time PCR. Pigs with sMR
      displayed markedly increased plasma proANP and SDMA concentrations compared with
      both controls and mMR (P<0.05). The expression of all genes examined differed
      significantly between the three localizations in the heart. miR-21 and miR-133a
      were differently expressed among the experimental groups (P<0.05). CONCLUSIONS:
      Plasma proANP and SDMA levels and tissue expression of miR-21 and miR-133a are
      associated with severity of chronic MR in an experimental porcine model.

PMID- 24029365
TI  - Molecular modeling of enzyme attachment on AFM probes.
AB  - The immobilization of enzymes on atomic force microscope tip (AFM tip) surface is
      a crucial step in the development of nanobiosensors to be used in detection
      process. In this work, an atomistic modeling of the attachment of the acetyl
      coenzyme A carboxylase (ACC enzyme) on a functionalized AFM tip surface is
      proposed. Using electrostatic considerations, suitable enzyme-surface
      orientations with the active sites of the ACC enzyme available for interactions
      with bulk molecules were found. A 50 ns molecular dynamics trajectory in aqueous
      solution was obtained and surface contact area, hydrogen bonding and protein
      stability were analyzed. The enzyme-surface model proposed here with minor
      adjustment can be applied to study antigen-antibody interactions as well as
      enzyme immobilization on silica for chromatography applications.

PMID- 24029366
TI  - Treatment with intravenous immunoglobulins in systemic lupus erythematosus: a
      series of 52 patients from a single centre.
AB  - OBJECTIVES: Some studies have shown efficacy of intravenous immunoglobulin (IVIG)
      in the treatment of systemic lupus erythematosus (SLE) but its use still lacks of
      confirmation in large cohorts. METHODS: This observational, retrospective, single
      centre clinical study included 52 SLE patients who received at least one cycle of
      IVIG (400 mg/kg/day for 5 days) from January 2001 to February 2011. Twenty-seven
      SLE patients were treated with IVIG for active disease and concomitant infection,
      while 26 received the IVIG as resistant to standard therapy. The indications for
      IVIG in the SLE patients were mainly cutaneous, haematological, neuropsychiatric
      and heart involvements. RESULTS: In patients with active disease and concomitant
      infections, the response to IVIG treatment was a complete remission (n=9),
      partial remission (n=8), and no response (n=8). We recorded any response (total
      or partial) in 17 out of 27 patients (62.96%). In patients with active disease
      refractory to standard therapy, the response to IVIG treatment was a complete
      remission (n=6), partial remission (n=12), and no response (n=8). We recorded any
      response (total or partial) in 18 out of 26 patients (69.23%). Seven of these
      patients relapsed after a mean time of 8.9 months (3-23 months). CONCLUSIONS: In
      a long-term study in the largest published cohort of SLE patients, IVIG was found
      to be effective in selected manifestations such as haematological and cardiac
      involvement or when other therapeutic approaches are not available, such as in
      patients with active disease and concomitant infection.

PMID- 24029367
TI  - CMR and LV noncompaction: does it matter how we measure trabeculations?

PMID- 24029369
TI  - Multimodality imaging, the wave of the future: multidiscipline attack on a
      complex disease.

PMID- 24029368
TI  - Libman-Sacks endocarditis and embolic cerebrovascular disease.
AB  - OBJECTIVES: The aim of this study was to determine whether Libman-Sacks
      endocarditis is a pathogenic factor for cerebrovascular disease (CVD) in systemic
      lupus erythematosus (SLE). BACKGROUND: A cardioembolic pathogenesis of SLE CVD
      manifested as: 1) neuropsychiatric systemic lupus erythematosus (NPSLE),
      including stroke and transient ischemic attacks (TIA); 2) neurocognitive
      dysfunction; and 3) magnetic resonance imaging of focal brain lesions has not
      been established. METHODS: A 6-year study of 30 patients with acute NPSLE (27
      women, 38 +/- 12 years of age), 46 age- and sex-matched SLE controls without
      NPSLE (42 women, 36 +/- 12 years of age), and 26 age- and sex-matched healthy
      controls (22 women, 34 +/- 11 years of age) who underwent clinical and laboratory
      evaluations, transesophageal echocardiography, carotid duplex ultrasound,
      transcranial Doppler ultrasound, neurocognitive testing, and brain magnetic
      resonance imaging/magnetic resonance angiography. Patients with NPSLE were re
      evaluated after 4.5 months of therapy. All patients were followed clinically for
      a median of 52 months. RESULTS: Libman-Sacks vegetations (87%),
      cerebromicroembolism (27% with 2.5 times more events per hour), neurocognitive
      dysfunction (60%), and cerebral infarcts (47%) were more common in NPSLE than in
      SLE (28%, 20%, 33%, and 0%) and healthy controls (8%, 0%, 4%, and 0%,
      respectively) (all p <= 0.009). Patients with vegetations had 3 times more
      cerebromicroemboli per hour, lower cerebral blood flow, more strokes/TIA and
      overall NPSLE events, neurocognitive dysfunction, cerebral infarcts, and brain
      lesion load than those without (all p <= 0.01). Libman-Sacks vegetations were
      independent risk factors of NPSLE (odds ratio [OR]: 13.4; p < 0.001),
      neurocognitive dysfunction (OR: 8.0; p = 0.01), brain lesions (OR: 5.6; p =
      0.004), and all 3 outcomes combined (OR: 7.5; p < 0.001). Follow-up re
      evaluations in 18 of 23 (78%) surviving patients with NPSLE demonstrated
      improvement of vegetations, microembolism, brain perfusion, neurocognitive
      dysfunction, and lesion load (all p <= 0.04). Finally, patients with vegetations
      had reduced event-free survival time to stroke/TIA, cognitive disability, or
      death (p = 0.007). CONCLUSIONS: The presence of Libman-Sacks endocarditis in
      patients with SLE was associated with a higher risk for embolic CVD. This
      suggests that Libman-Sacks endocarditis may be a source of cerebral emboli.

PMID- 24029370
TI  - Clinical utility and prognostic value of appropriateness criteria in stress
      echocardiography for the evaluation of valvular heart disease.
AB  - We examined the prognostic value of stress echocardiography appropriateness
      criteria for evaluation of valvular heart disease in 100 consecutive patients. Of
      the studies, 49%, 36%, and 15% were classified as appropriate, uncertain, and
      inappropriate, respectively. Over a median of 12.6 months, 24 events (12 deaths
      and 12 heart failure admissions) occurred. The 12-month event-free survival was
      significantly reduced in patients with appropriate or uncertain studies compared
      with patients with inappropriate studies (p = 0.04 and p = 0.005, respectively).
      There was no survival difference between patients with an appropriate or
      uncertain indication (p = 0.1). The only independent predictors of events were a
      positive stress echocardiogram (hazard ratio: 15.5, p < 0.0001) and left
      ventricular ejection fraction (hazard ratio: 0.95, p = 0.02). The appropriateness
      criteria for evaluation of valvular heart disease provide the ability to
      differentiate between patients at high- (appropriate group) and low-
      (inappropriate group) risk of cardiac events. Reclassification of the uncertain
      group may improve the differential value of these criteria.

PMID- 24029371
TI  - Cardiac imaging and stress testing asymptomatic athletes to identify those at
      risk of sudden cardiac death.
AB  - Sudden cardiac death in young athletes is rare but tragic. The cardiology
      community is faced with the challenge of providing a sensible strategy for the
      prevention of SCD while simultaneously reaffirming that the benefits of regular
      exercise far outweigh potential risks. At present, there is a broad range of
      screening recommendations dependent upon country, sporting discipline, and
      competition level. While much recent debate has focused on the efficacy of
      screening with electrocardiography, a number of sporting bodies also mandate the
      inclusion of exercise testing and echocardiography in screening protocols.
      Cardiac magnetic resonance imaging, coronary calcium scoring and computed
      tomography coronary angiography have also been promoted as potentially valuable
      screening tools for competitive athletes. This review will examine the
      controversial topic of utilizing cardiac imaging for athlete pre-participation
      screening. Specifically, the limitations of screening for relatively rare
      disorders using imaging tools with uncertain or imperfect accuracy will be
      addressed. Current evidence suggests that the accuracy of all cardiac imaging
      modalities is insufficient to justify their use as primary screening modalities
      in athletes. Atypical findings such as marked cardiac dilation, reduced
      deformation, or small patches of delayed gadolinium enhancement may be commonly
      encountered in well-trained athletes, but, at present, the prognostic
      significance of such findings is unknown. Resulting uncertainty for the clinician
      and athlete has the potential for psychological stress, further testing, and
      unnecessary exclusions from competition. However, these concerns must not be
      confused with the extremely useful applications of cardiac imaging for the
      assessment of athletes with symptoms, an abnormal electrocardiogram or a positive
      family history. As modern imaging further enhances our understanding of the
      spectrum of athlete's heart, its role may expand from the assessment of athletes
      with suspected disease to being part of comprehensive pre-participation screening
      in apparently healthy athletes. 

PMID- 24029372
TI  - CT angiography and 18F-FDG-PET fusion imaging for prosthetic heart valve
      endocarditis.

PMID- 24029373
TI  - Predicting impending rupture of the ascending aorta with bicuspid aortic valve:
      spatiotemporal flow and wall shear stress.

PMID- 24029374
TI  - Adding or selecting imaging modalities for incremental diagnosis: a case study of
      18FDG PET/CT in prosthetic valve endocarditis.

PMID- 24029375
TI  - Multimodality imaging: opportunities and challenges.

PMID- 24029376
TI  - Intraoperative electrical stimulation of language switching in two bilingual
      patients.
AB  - BACKGROUND: Language switching (LS) is an important phenomena usually observed in
      some bilingual communities. The ability to switch languages is a very fast,
      efficient and flexible process, being a fundamental aspect of bilingual efficient
      language communication. The aim of the present study was to characterize the
      specific role of non-language specific prefrontal regions in the neural network
      involved in LS in bilingual patients, during awake brain surgery and using
      electrical stimulation mapping (ESM). METHODS: In order to identify the neural
      regions involved in LS we used, a new specific ESM protocol in two patients
      undergoing awake brain surgery. Besides, functional magnetic resonance imaging
      (fMRI), neuropsychological testing and the assessment of daily conversational LS
      patterns post-surgery were used as complementary imaging and behavioral
      assessments. RESULTS: The outcome of the multimodal ESM-fMRI neuroimaging
      comparison in both patients pointed out to the crucial involvement of the
      inferior and middle frontal cortices in LS. CONCLUSIONS: The present results add
      to previous findings highlighting the important role of non-language specific
      frontal structures in regulating LS. The new protocol developed here might allow
      neurosurgeons to plan ahead for surgical intervention in multilingual patients to
      ensure the preservation of regions involved in LS and therefore the prevention of
      pathological language mixing after intervention.

PMID- 24029377
TI  - Overlapping neural circuitry for narrative comprehension and proficient reading
      in children and adolescents.
AB  - Narrative comprehension is a perinatal linguistic ability which is more intuitive
      than reading activity. Whether there are specific shared brain regions for
      narrative comprehension and reading that are tuned to reading proficiency, even
      before reading is acquired, is the question of the current study. We acquired
      fMRI data during a narrative comprehension task at two age points, when children
      are age 5-7 (K-2nd grade) and later when the same children were age 11 (5th-7th
      grade). We then examined correlations between this fMRI data and reading and
      reading comprehension scores from the same children at age 11. We found that
      greater frontal and supramarginal gyrus (BA 40) activation in narrative
      comprehension at the age of 5-7 years old was associated with better word reading
      and reading comprehension scores at the age of 11. A shift towards temporal and
      occipital activation was found when correlating their narrative comprehension
      functional data at age 11, with reading scores at the same age point. We suggest
      that increased reliance on executive functions and auditory-visual networks when
      listening to stories before reading is acquired, facilitates reading proficiency
      in older age and may be a biomarker for future reading ability. Children, who
      rely on use of imagination/visualization as well as auditory processing for
      narrative comprehension when they reach age 11, also show greater reading
      abilities. Understanding concordant neural pathways supporting auditory narrative
      and reading comprehension might be guide for development of effective tools for
      reading intervention programs. 

PMID- 24029378
TI  - Symmetry detection in typically and atypically speech lateralized individuals: a
      visual half-field study.
AB  - Visuospatial functions are typically lateralized to the right cerebral
      hemisphere, giving rise to a left visual field advantage in visual half-field
      tasks. In a first study we investigated whether this is also true for symmetry
      detection off fixation. Twenty right-handed participants with left hemisphere
      speech dominance took part in a visual half-field experiment requiring them to
      judge the symmetry of 2-dimensional figures made by joining rectangles in
      symmetrical or asymmetrical ways. As expected, a significant left visual field
      advantage was observed for the symmetrical figures. In a second study, we
      replicated the study with 37 left-handed participants and left hemisphere speech
      dominance. We again found a left visual field advantage. Finally, in a third
      study, we included 17 participants with known right hemisphere dominance for
      speech (speech dominance had been identified with fMRI in an earlier study; Van
      der Haegen, Cai, Seurinck, & Brysbaert, 2011). Around half of these individuals
      showed a reversed pattern, i.e. a right visual half-field advantage for symmetric
      figures while the other half replicated the left visual-field advantage. These
      findings suggest that symmetry detection is indeed a cognitive function
      lateralized to the right hemisphere for the majority of the population. The data
      of the participants with atypical speech dominance are more in line with the idea
      that language and visuospatial functions are lateralized in opposite brain
      hemispheres than with the idea that different functions lateralize independently,
      although there seems to be more variability in this group. 

PMID- 24029379
TI  - Use of oral budesonide in the management of protein-losing enteropathy due to
      restrictive cardiomyopathy.
AB  - A 7-year-old male patient who had abdominal swelling and eyelid oedema was
      diagnosed with restrictive cardiomyopathy. His serum albumin level was 2.3 g/dl.
      Protein-losing enteropathy due to restrictive cardiomyopathy was diagnosed and
      oral budesonide was started. His serum albumin level began to rise and ascites
      and peripheric oedema disappeared. The patient underwent a successful cardiac
      transplantation and budesonide was stopped. After the heart transplantation, the
      albumin level decreased to 2.3 g/dl, and therefore it was restarted. When the
      serum albumin level increased, the budesonide dose was tapered and stopped in 1
      month. Budesonide may be an effective drug in patients with protein-losing
      enteropathy due to heart failure. 

PMID- 24029380
TI  - Preserving the Q-factors of ZnO nanoresonators via polar surface reconstruction.
AB  - We perform molecular dynamics simulations to investigate the effect of polar
      surfaces on the quality (Q)-factors of zinc oxide (ZnO) nanowire-based
      nanoresonators. We find that the Q-factors in ZnO nanoresonators with free polar
      (0001) surfaces are about one order of magnitude higher than in nanoresonators
      that have been stabilized with reduced charges on the polar (0001) surfaces. From
      normal mode analysis, we show that the higher Q-factor is due to a shell-like
      reconstruction that occurs for the free polar surfaces. This shell-like
      reconstruction suppresses twisting motion in the nanowires such that the mixing
      of other modes with the resonant mode of oscillation is minimized, and leads to
      substantially higher Q-factors in ZnO nanoresonators with free polar surfaces. 

PMID- 24029381
TI  - Bioactive components of velvet antlers and their pharmacological properties.
AB  - Velvet antler is one of the most important animal medicines, and has been used
      with a variety of functions, such as anti-fatigue, tissue repair and health
      promotion. In the past few years, the investigation on chemical compositions,
      bioactive components, and pharmacological effects has been performed, which
      demonstrates that velvet antlers could be used as an important health-promoting
      tonic with great nutritional and medicinal values. This review focuses on the
      recent advance in studying the bioactive components of velvet antlers. 

PMID- 24029382
TI  - Fusobacterium spp. and colorectal cancer: cause or consequence?
AB  - Although increasing evidence suggests a relationship between bacterial dysbiosis
      and colorectal cancer (CRC), few studies have identified specific microbial
      etiologic factors. Recent studies have implicated overabundance of Fusobacterium
      in association with colorectal adenomas and cancer. Two articles published in
      Cell Host & Microbe provide insights into the Fusobacterium-CRC relationship. 

PMID- 24029384
TI  - Safety of 20-gauge transconjunctival sutureless vitrectomy.
AB  - PURPOSE: To study the safety of 20-gauge transconjunctival sutureless vitrectomy.
      METHODS: Clinical data of patients who underwent 20-gauge transconjunctival
      sutureless vitrectomy for the first time, for various disorders, were reviewed
      retrospectively. The main outcome measures were the number of sclerotomies
      requiring suturing as well as the intra- and postoperative complications.
      RESULTS: A total of 179 operations were performed. Indications for vitrectomy
      included 68 idiopathic epiretinal membranes, 26 macular holes, 23 phakic and 16
      pseudophakic retinal detachments, and 46 various other, less common etiologies.
      Of these 179 operations, 166 (93%) were sutureless. Of the 537 sclerotomies
      created, 25 (5%) received a single transconjunctival-scleral suture.
      Intraoperative complications included premature dislodging of the cannulas in 2
      sclerotomies and an iatrogenic horseshoe tear at 1 sclerotomy site. Postoperative
      complications comprised transient hypotony in 14 cases, subconjunctival gas in 2
      cases, and choroidal effusion in 1 case. No serious complications (such as
      endophthalmitis) were observed. CONCLUSION: 20-gauge transconjunctival sutureless
      vitrectomy can be considered safe, as the intra- and postoperative complications
      observed are neither numerous nor significant. Sclerotomies appear to be safe and
      relatively easy to perform, without compromising the advantages of sutureless
      surgery.

PMID- 24029383
TI  - Nrf2 is essential for the expression of lipocalin-prostaglandin D synthase
      induced by prostaglandin D2.
AB  - Nrf2 is a transcription factor that protects against inflammatory diseases, but
      the underlying mechanism of this effect remains unclear. Here, we report that
      Nrf2 uses lipocalin-prostaglandin D synthase (L-PGDS) as a mechanism for
      suppressing inflammation. Exogenously added prostaglandin D2 (PGD2) induced L
      PGDS expression in bone-marrow-derived macrophages (BMDMs), suggesting a positive
      feedback loop between L-PGDS expression and PGD2. Unlike lipopolysaccharide (LPS)
      induced L-PGDS expression, PGD2-mediated expression was independent of MAPK,
      PU.1, or TLR4. Sequence analysis located a putative Nrf2 binding site in the
      murine L-PGDS promoter, to which Nrf2 bound when treated with PGD2. Chemical
      activation, or overexpression, of Nrf2 was sufficient to induce L-PGDS expression
      in macrophages, BMDMs, or lungs of Nrf2-knockout (KO) mice, but treatment with
      PGD2 failed to do so, suggesting a pivotal role for Nrf2 in the expression of L
      PGDS. Consistent with this, expression of Nrf2 in the lungs of Nrf2-KO mice was
      sufficient to induce the expression of L-PGDS and to reduce neutrophilic lung
      inflammation elicited by LPS. Furthermore, expression of L-PGDS in mouse lungs
      decreased neutrophilic infiltration, ameliorating lung inflammation in mice.
      Together, our results show that Nrf2, activated by PGD2, induced L-PGDS
      expression, resulting in decreased inflammation. We suggest that the positive
      feedback induction of L-PGDS by PGD2 is part of the mechanism by which Nrf2
      regulates inflammation. 

PMID- 24029385
TI  - Liver-specific microRNAs as biomarkers of nanomaterial-induced liver damage.
AB  - Although nanomaterials are being used in various fields, their safety is not yet
      sufficiently understood. We have been attempting to establish a nanomaterials
      safety-assessment system by using biomarkers to predict nanomaterial-induced
      adverse biological effects. Here, we focused on microRNAs (miRNAs) because of
      their tissue-specific expression and high degree of stability in the blood. We
      previously showed that high intravenous doses of silica nanoparticles of 70 nm
      diameter (nSP70) induced liver damage in mice. In this study, we compared the
      effectiveness of serum levels of liver-specific or -enriched miRNAs (miR-122, miR
      192, and miR-194) with that of conventional hepatic biomarkers (alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST)) as biomarkers for
      nSP70. After mice had been treated with nSP70, their serum miRNAs levels were
      measured by using quantitative RT-PCR. Serum levels of miR-122 in nSP70-treated
      mice were the highest among the three miRNAs. The sensitivity of miR-122 for
      liver damage was at least as good as those of ALT and AST. Like ALT and AST, miR
      122 may be a useful biomarker of nSP70. We believe that these findings will help
      in the establishment of a nanomaterials safety-assessment system.

PMID- 24029386
TI  - Validation of a method to assess range of motion of the cervical spine using a
      tape measure.
AB  - OBJECTIVE: The purposes of this study were to validate a tape measure method for
      measuring cervical spine range of motion compared with a universal goniometer in
      all planes of motion and to derive equations to convert a linear measurement to
      an angular distance. METHODS: Participants were healthy volunteers. Measurements
      of flexion/extension, rotation, and lateral flexion were made with the universal
      goniometer and tape measure, in the neutral position, extreme of motion, and 2
      positions between. Measurements from the 2 techniques were compared with Pearson
      correlation coefficient and simple linear regression to determine R(2), the
      regression coefficient and the regression equation. Reliability was assessed
      using the intraclass correlation coefficient. RESULTS: There were 40 participants
      with a mean age of 30.5 (SD, 9.1) years. Goniometer measurements had good to
      excellent correlation with both absolute and percentage change in tape
      measurement (correlation coefficients, 0.74-0.94 and 0.75-0.91, respectively).
      Correlation was highest for flexion and extension, lowest for rotation and
      lateral flexion. The amount of variability in the data explained by the linear
      regression models (R(2)) varied from 55% to 89%. Intraclass correlation
      coefficient ranged from 0.44 to 0.69 and 0.38 to 0.59 for intrarater and
      interrater reliability, respectively. Reliability was greatest for flexion and
      extension, lowest for rotation and lateral flexion. CONCLUSION: This study
      demonstrated that tape measurements correlated well with a universal goniometer.
      The tape measure may be useful for measuring cervical spine range of motion where
      availability, simplicity, and low cost are important considerations such as with
      conduct of research or patient management.

PMID- 24029387
TI  - Frequency of discordance between facet joint activity on technetium Tc99m
      methylene diphosphonate SPECT/CT and selection for percutaneous treatment at a
      large multispecialty institution.
AB  - BACKGROUND AND PURPOSE: The clinical impact of facet joint bone scan activity is
      not fully understood. The hypothesis of this study is that facet joints targeted
      for percutaneous treatment in clinical practice differ from those with reported
      activity on technetium Tc99m methylene diphosphonate SPECT/CT. MATERIALS AND
      METHODS: All patients with a technetium Tc99m methylene diphosphonate SPECT/CT
      scan of the lumbar or cervical spine who underwent subsequent percutaneous facet
      joint steroid injection or comparative medial branch blocks at our institution
      between January 1, 2008, and February 19, 2013, were identified. Facet joints
      with increased activity were compared with those treated. A chart review
      characterized the clinical reasons for treatment discrepancies. RESULTS: Of 74
      patients meeting inclusion criteria, 52 (70%) had discrepant imaging findings and
      treatment selection of at least 1 facet joint, whereas 34 patients (46%) had a
      side (right vs left) discrepancy. Only 92 (70%) of 132 facet joints with
      increased activity were treated, whereas 103 (53%) of 195 of treated facet joints
      did not have increased activity. The most commonly documented clinical rationale
      for discrepancy was facet joint activity that was not thought to correlate with
      clinical findings, cited in 18 (35%) of 52 patients. CONCLUSIONS: Facet joints
      undergoing targeted percutaneous treatment were frequently discordant with those
      demonstrating increased technetium Tc99m methylene diphosphonate activity
      identified by SPECT/CT at our institution, in many cases because the active facet
      joint(s) did not correlate with clinical findings. Further prospective double
      blinded investigations of the clinical significance of facet joint activity by
      use of technetium Tc99m methylene diphosphonate SPECT/CT and comparative medial
      branch blocks are needed.

PMID- 24029388
TI  - Multivariate classification of blood oxygen level-dependent FMRI data with
      diagnostic intention: a clinical perspective.
AB  - SUMMARY: There has been a recent upsurge of reports about applications of pattern
      recognition techniques from the field of machine learning to functional MR
      imaging data as a diagnostic tool for systemic brain disease or psychiatric
      disorders. Entities studied include depression, schizophrenia, attention deficit
      hyperactivity disorder, and neurodegenerative disorders like Alzheimer dementia.
      We review these recent studies which-despite the optimism from some articles
      predominantly constitute explorative efforts at the proof-of-concept level. There
      is some evidence that, in particular, support vector machines seem to be
      promising. However, the field is still far from real clinical application, and
      much work has to be done regarding data preprocessing, model optimization, and
      validation. Reporting standards are proposed to facilitate future meta-analyses
      or systematic reviews.

PMID- 24029389
TI  - A meta-analysis on the diagnostic performance of (18)F-FDG and (11)C-methionine
      PET for differentiating brain tumors.
AB  - SUMMARY: (18)F-FDG-PET has been widely used in patients with brain tumors.
      However, the reported sensitivity and specificity of (18)F-FDG-PET for brain
      tumor differentiation varied greatly. We performed this meta-analysis to
      systematically assess the diagnostic performance of (18)F-FDG-PET in
      differentiating brain tumors. The diagnostic performance of (11)C-methionine PET
      was assessed for comparison. Relevant studies were searched in PubMed/MEDLINE,
      Scopus, and China National Knowledge Infrastructure (until February 2013). The
      methodologic quality of eligible studies was evaluated, and a meta-analysis was
      performed to obtain the combined diagnostic performance of (18)F-FDG and (11)C
      methionine PET with a bivariate model. Thirty eligible studies, including 5
      studies with both (18)F-FDG and (11)C-methionine PET data were enrolled. Pooled
      sensitivity, pooled specificity, and area under the receiver operating
      characteristic curve of (18)F-FDG-PET (n = 24) for differentiating brain tumors
      were 0.71 (95% CI, 0.63-0.78), 0.77 (95% CI, 0.67-0.85), and 0.80. Heterogeneity
      was found among (18)F-FDG studies. Subsequent subgroup analysis revealed that the
      disease status was a statistically significant source of the heterogeneity and
      that the sensitivity in the patients with recurrent brain tumor was markedly
      higher than those with suspected primary brain tumors. Pooled sensitivity, pooled
      specificity, and area under the receiver operating characteristic of (11)C
      methionine PET (n = 11) were 0.91 (95% CI, 0.85-0.94), 0.86 (95% CI, 0.78-0.92),
      and 0.94. No significant statistical heterogeneity was found among (11)C
      methionine studies. This meta-analysis suggested that (18)F-FDG-PET has limited
      diagnostic performance in brain tumor differentiation, though its performance may
      vary according to the status of brain tumor, whereas (11)C-methionine PET has
      excellent diagnostic accuracy in brain tumor differentiation.

PMID- 24029390
TI  - Volumetric assessment of optic nerve sheath and hypophysis in idiopathic
      intracranial hypertension.
AB  - BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is a headache
      syndrome characterized by increased CSF pressure. Compression of the hypophysis
      and distension of the optic nerve sheath are reliable imaging signs. The purpose
      of the study was to validate, in patients with idiopathic intracranial
      hypertension, MR imaging-based volumetric measurements of the optic nerve sheath
      and hypophysis as an objective observation method for more accurate diagnosis and
      posttreatment follow-up. MATERIALS AND METHODS: Twenty-three patients with
      idiopathic intracranial hypertension as well as age-, sex-, and body mass index
      matched controls underwent volumetric measurements of the optic nerve, optic
      nerve sheath, and hypophysis on high-resolution T2-weighted MR images by using a
      7-cm surface coil, followed by correlation with CSF opening pressures and
      clinical symptom scores of visual disturbances and headache. RESULTS: Mean values
      of optic nerve sheath (341.86 +/- 163.69 mm(3) versus 127.56 +/- 53.17 mm(3), P <
      .001) and hypophysis volumes (554.59 +/- 142.82 mm(3) versus 686.60 +/- 137.84
      mm(3), P < .05) differed significantly between healthy and diseased subjects. No
      significant differences between mean optic nerve volumes were observed. Receiver
      operating characteristic analysis showed optic nerve sheath volumes of >201.30
      mm(3) (sensitivity, 86.96%; specificity, 91.30%) and hypophysis volumes of
      <611.21 mm(3) (sensitivity, 78.26%; specificity, 69.57%) to be indicative of
      idiopathic intracranial hypertension diagnosis. In patients with idiopathic
      intracranial hypertension, no correlations were found between optic nerve sheath
      and hypophysis volumes and CSF opening pressures or clinical scores of visual
      disturbances and headache. CONCLUSIONS: Semiautomated volumetric measurement of
      optic nerve sheath and hypophysis has the potential to more accurately diagnose
      and follow patients with idiopathic intracranial hypertension.

PMID- 24029391
TI  - Fractional change in apparent diffusion coefficient as an imaging biomarker for
      predicting treatment response in head and neck cancer treated with
      chemoradiotherapy.
AB  - BACKGROUND AND PURPOSE: ADC provides a measure of water molecule diffusion in
      tissue. The aim of this study was to evaluate whether the fractional change in
      ADC during therapy can be used as a valid predictive indicator of treatment
      response in head and neck squamous cell carcinoma treated with chemoradiotherapy.
      MATERIALS AND METHODS: Forty patients underwent DWI at pretreatment and 3 weeks
      after the start of treatment. The pretreatment ADC, fractional change in ADC,
      tumor regression rate, and other clinical variables were compared with
      locoregional control and locoregional failure and were analyzed by using logistic
      regression analysis and receiver operating characteristic analysis. Furthermore,
      progression-free survival curves divided by the corresponding threshold value
      were compared by means of the log-rank test. RESULTS: The fractional change in
      ADCprimary, the fractional change in ADCnode, primary tumor volume, nodal volume,
      tumor regression ratenode, N stage, and tumor location revealed significant
      differences between locoregional failure and locoregional control (P < .05). In
      univariate analysis, the fractional change in ADCprimary, fractional change in
      ADCnode, tumor regression ratenode, N stage, and tumor location showed
      significant association with locoregional control (P < .05). In multivariate
      analysis, however, only the fractional change in ADCprimary was identified as a
      significant and independent predictor of locoregional control (P = .04). A
      threshold fractional change in ADCprimary of 0.24 revealed a sensitivity of 100%,
      specificity of 78.7%, and overall accuracy of 84.8% for the prediction of
      locoregional control. Progression-free survival of the 2 groups divided by the
      fractional change in ADCprimary at 0.24 showed a significant difference (P <
      .05). CONCLUSIONS: The results suggest that the fractional change in ADCprimary
      is a valid imaging biomarker for predicting treatment response in head and neck
      squamous cell carcinoma treated with chemoradiotherapy.

PMID- 24029392
TI  - Complications of endovascular treatment for acute stroke in the SWIFT trial with
      solitaire and Merci devices.
AB  - BACKGROUND AND PURPOSE: Treatment of patients with ischemic stroke after
      endovascular treatment requires in-depth knowledge of complications. The goal of
      this study was to make endovascular treatment for acute ischemic stroke safer
      through an in-depth review of the major periprocedural complications observed in
      the Solitaire FR With Intention for Thrombectomy (SWIFT) trial. MATERIALS AND
      METHODS: The SWIFT data base was searched for major peri-procedural complications
      defined as symptomatic intracranial hemorrhage within 36 hours, SAH, air emboli,
      vessel dissection, major groin complications, and emboli to new vascular
      territories. RESULTS: Major peri-procedural complications occurred in 18 of 144
      patients (12.5%) as follows: symptomatic intracranial hemorrhage, 4.9%; air
      emboli, 1.4%; vessel dissection, 4.2%; major groin complications, 2.8%; and
      emboli to new vascular territories, 0.7%. Rates of symptomatic intracranial
      bleeding by subtype were PH1, 0.7%; PH2, 0.7% (PH1 indicates hematoma within
      ischemic field with some mild space-occupying effect but involving <= 30% of the
      infarcted area; PH2, hematoma within ischemic field with space-occupying effect
      involving >30% of the infarcted area); intracranial hemorrhage remote from
      ischemic zone, 0%; intraventricular hemorrhage, 0.7%; and SAH, 3.5%. We did not
      observe any statistically significant associations of peri-procedural
      complications with age; type of treatment center; duration of stroke symptoms;
      NIHSS score, IV thrombolytics, atrial fibrillation, site of vessel occlusion;
      rescue therapy administered after endovascular treatment; or device. Comparing
      the Merci with the Solitaire FR retrieval device, we observed symptomatic
      cerebral hemorrhage (10.9% versus 1.1%; P = .013); symptomatic SAH (7.3% versus
      1.1%; P = .07), air emboli (1.8% versus 1.1%; P = 1.0), emboli to new vascular
      territories (1.8% versus 0%; P = .38), vessel dissection (1.8% versus 4.5%; P =
      .65), and major groin complications (3.6% versus 7.9%; P = .48). Angiographic
      vasospasm was common but without clinical sequelae. CONCLUSIONS: Understanding of
      procedural complications is important for treatment of patients with stroke after
      endovascular treatment. We observed fewer endovascular complications with the
      Solitaire FR device treatment compared with Merci device treatment, particularly
      symptomatic cerebral hemorrhage.

PMID- 24029393
TI  - CFD: computational fluid dynamics or confounding factor dissemination? The role
      of hemodynamics in intracranial aneurysm rupture risk assessment.
AB  - Image-based computational fluid dynamics holds a prominent position in the
      evaluation of intracranial aneurysms, especially as a promising tool to stratify
      rupture risk. Current computational fluid dynamics findings correlating both high
      and low wall shear stress with intracranial aneurysm growth and rupture puzzle
      researchers and clinicians alike. These conflicting findings may stem from
      inconsistent parameter definitions, small datasets, and intrinsic complexities in
      intracranial aneurysm growth and rupture. In Part 1 of this 2-part review, we
      proposed a unifying hypothesis: both high and low wall shear stress drive
      intracranial aneurysm growth and rupture through mural cell-mediated and
      inflammatory cell-mediated destructive remodeling pathways, respectively. In the
      present report, Part 2, we delineate different wall shear stress parameter
      definitions and survey recent computational fluid dynamics studies, in light of
      this mechanistic heterogeneity. In the future, we expect that larger datasets,
      better analyses, and increased understanding of hemodynamic-biologic mechanisms
      will lead to more accurate predictive models for intracranial aneurysm risk
      assessment from computational fluid dynamics.

PMID- 24029394
TI  - Local or systemic treatment for New World cutaneous leishmaniasis? Re-evaluating
      the evidence for the risk of mucosal leishmaniasis.
AB  - This review addresses the question of whether the risk of developing mucosal
      leishmaniasis (ML) warrants systemic treatment in all patients with New World
      cutaneous leishmaniasis (CL) or whether local treatment might be an acceptable
      alternative. The risk of patients with New World CL developing ML after the
      initial infection has been the main argument for systemic treatment. However,
      this statement needs re-evaluation and consideration of all the available data.
      The putative benefit of preventing ML should outweigh the toxicity of systemic
      antileishmanial therapy. To assess the need for and risk of systemic treatment
      the following factors were reviewed: the incidence and prevalence of ML in
      endemic populations and in travellers; the severity of mucosal lesions; the
      efficacy of current options to treat ML; the toxicity and, to a lesser extent,
      the costs of systemic treatment; the risk of developing ML after local treatment;
      and the strengths and limitations of current estimates of the risk of developing
      ML in different situations. Local treatment might be considered as a valuable
      treatment option for travellers suffering from New World CL, provided that there
      are no risk factors for developing ML such as multiple lesions, big lesions (>4
      cm(2)), localisation of the lesion on the head or neck, immunosuppression or
      acquisition of infection in the high Andean countries, notably Bolivia.

PMID- 24029395
TI  - Changes in knowledge and practices related to taeniasis/cysticercosis after
      health education in a south Indian community.
AB  - A health education programme for taeniasis/cysticercosis was implemented and
      evaluated among schoolchildren and the general community in a rural block in
      southern India, an area that is endemic for cysticercosis. The baseline survey
      among 831 participants from three randomly selected villages showed poor
      knowledge regarding the spread of taeniasis and neurocysticercosis. There was
      also a lack of adequate hygiene and sanitation practices. Health education was
      given in these villages and in the schools located in these villages regarding
      the lifecycle of the pork tapeworm, spread of taeniasis and cysticercosis, and
      prevention of these conditions. The post-intervention test conducted 6 months
      later among 1060 participants revealed a 46% increase in the overall score of
      knowledge and practices. Awareness about the mode of spread of taeniasis and
      cysticercosis improved by almost 3 times and the reported practice of washing
      hands with soap and water before eating improved by 4.8 times and after using the
      toilet by 3.6 times. One person who reported the passage of tapeworm segments was
      confirmed to be a carrier of Taenia solium and was treated. The health education
      given on prevention of taeniasis and cysticercosis was useful in improving the
      knowledge and practices of the community and also in diagnosing taeniasis through
      self-reporting.

PMID- 24029396
TI  - Feasibility and benefits of scaling up antiretroviral treatment provision with
      the 2010 WHO antiretroviral therapy guidelines in rural Lesotho.
AB  - The latest WHO guidelines (2010) for antiretroviral therapy (ART) in adults and
      adolescents recommend that countries should progressively reduce the use of
      stavudine in favour of tenofovir or zidovudine and that ART initiation commence
      at an earlier CD4 threshold of <350 cell/mm(3). In Lesotho, a high-burden,
      resource-limited setting, these two changes had been recommended since late 2007.
      A number of practical steps were taken to support implementation of Lesotho's
      national ART guidelines at the program level including: development of guidelines
      tailored to nurses working in primary care settings; training and clinical
      mentorship of different levels of health care workers; laboratory support;
      pharmacy support; and monitoring and evaluation. Clinical and programmatic
      benefits included decreased mortality, toxicity, and simplified patient
      management that was supportive of the decentralized, nurse-led model of care.
      This experience demonstrates that, despite limited resources, it was feasible to
      provide a standard of care similar to that of western guidelines and that these
      changes were supportive of simplified patient management.

PMID- 24029397
TI  - Strategies developed and implemented by women's groups to improve mother and
      infant health and reduce mortality in rural Malawi.
AB  - We evaluated the strategies to tackle maternal and infant health problems
      developed by women's groups in rural Malawi. Quantitative data were analyzed on
      strategies developed by 184 groups at two of the meetings in the community action
      cycle (attended by 3365 and 3047 women). Data on strategies implemented was
      collected through a survey of the 197 groups active in January 2010. Qualitative
      data on the identification and implementation of strategies was collected through
      17 focus group discussions and 12 interviews with men and women. To address the
      maternal and child health problems identified the five most common strategies
      identified were: health education sessions, bicycle ambulances, training of
      traditional birth attendants, wetland vegetable garden (dimba garden) cultivation
      and distribution of insecticide treated bednets (ITNs). The five most common
      strategies actually implemented were: dimba garden cultivation, health education
      sessions, ITN distribution, health programme radio listening clubs and clearing
      house surroundings. The rationale behind the strategies and the factors
      facilitating and hindering implementation are presented. The potential impact of
      the strategies on health is discussed. Women's groups help communities to take
      control of their health issues and have the potential to reduce neonatal, infant
      and maternal mortality and morbidity in the longer term.

PMID- 24029398
TI  - Patient perspectives on opt-out HIV screening in a Guyanese emergency department.
AB  - In 2007, the WHO recommended that healthcare providers in areas of a generalised
      HIV epidemic perform HIV testing on all adults and adolescents presenting for
      healthcare. Studies regarding patient acceptability of opt-out testing, however,
      have reported wide variation in acceptance rates. This study examines patient
      reported acceptability of such testing at the emergency department (ED) of
      Georgetown Public Hospital Corporation, the largest public hospital in Guyana. In
      June 2010, a convenience sample of 343 non-critical adult patients who presented
      to the ED were interviewed regarding potential acceptance of opt-out HIV testing,
      with 75.5% (95% CI 70.5-80.0%) stating they would accept testing should it be
      implemented in the ED. Of 12 patient characteristics, 3 had significant
      differences in acceptance rates on multivariate analysis: age; gender; and
      previous HIV testing. In this study, potential reasons for declining testing were
      also examined. The highest percentage of patient agreement was with the
      statements 'I have had an HIV test recently enough' (84%, 95% CI 74.0-91.4%) and
      'I am not at risk for HIV/AIDS' (83%, 95% CI 73.0-90.4%). The results of this
      study indicate that the majority of patients in this setting would accept opt-out
      HIV testing, although some still had concerns regarding testing. Opt-out testing
      in the ED has the potential to facilitate national goals for increased testing
      and diagnosis.

PMID- 24029399
TI  - Location and vocation: why some government doctors stay on in rural Chhattisgarh,
      India.
AB  - We conducted a qualitative research study in Chhattisgarh State, India, to
      explore why some qualified medical practitioners decide to stay on in government
      rural service. The fieldwork consisted of in-depth interviews with 37
      practitioners who had an established record of rural service, and data were
      analyzed using the 'framework' approach for applied policy research. Study
      participants cited complexes of reasons for staying on, including geographical
      and ethnic (tribal) affinities, rural upbringing, availability of schools,
      personal values of service, professional interests, co-location with spouses, and
      relations with co-workers. Extrinsic (environmental) and intrinsic (personal)
      factors both play a part in determining the decisions of doctors to stay on, and
      are interdependent. Some doctors were influenced to remain by the close
      relationships they had developed with local communities and their acclimatisation
      over time to rural life. The policy imperative of rural workforce adequacy may be
      served less by choosing one retention strategy over another than by developing
      multi-dimensional solutions focused simultaneously on identifying and
      incentivising rural practitioners with appropriate characteristics, and on
      creating external conditions for their improved performance and welfare. Further,
      in a low-income setting such as India, questions of rural workforce adequacy
      cannot be addressed in isolation, but need to be tackled as part of broad agenda
      of social development that include strengthening public service systems and
      empowering communities.

PMID- 24029400
TI  - Attitudes of married men to the use of vaginal microbicides by their female
      partners in Pune, India.
AB  - The availability of female-initiated HIV prevention options does not necessarily
      lead to their uptake. We investigated if married men were willing to support open
      or covert use of microbicides by their spouses in Pune, India. Data was collected
      using an interview-administered questionnaire from 151 consenting married men
      with a mean age of 34 years. Logistic regression analysis was used to examine the
      relationships between sociodemographic and behavioural factors. One hundred and
      thirty-seven men (71.5%) were educated and 146 men (96.7%) were employed. Men
      aged <34 years were eight times (p=0.024) and those in a harmonious relationship
      were seven times (p=0.008) more willing to use microbicides compared with men
      aged >=34 years and men in less harmonious relationships, respectively. Men
      practicing high-risk sexual behaviour were twice (p=0.049) and men with a history
      of using contraceptives were three times (p=0.05) more likely to support the
      covert use of microbicides compared with those reporting no or low-risk sexual
      behaviour and those who had never used contraceptives, respectively. This
      suggests that sociodemographic and behavioural factors relating to men as well as
      women should be considered when developing and marketing microbicides.

PMID- 24029401
TI  - Is areca innocent? The effect of areca (betel) nut chewing in a population of
      pregnant women on the Thai-Myanmar border.
AB  - Eight manuscripts have specifically examined the effects of areca (betel) nut use
      in pregnant women, seven of which have documented adverse effects on birth
      weight, newborn neurological status, gender ratio and pregnancy outcomes such as
      anaemia and miscarriage following areca nut use during pregnancy. A retrospective
      cohort analysis of migrant and refugee pregnant women attending antenatal clinics
      along the Thai-Myanmar border (July 1997 to November 2006) was conducted to
      examine the adverse effects of areca nut use routinely recorded on enrolment. Of
      7685 women, 2284 (29.7%) never used areca or smoked (cheroots), 2484 (32.3%) only
      used areca, 438 (5.7%) only smoked cheroots and 2479 (32.3%) used both areca and
      cheroots. Pieces of ripe areca nut in a leaf with lime, without tobacco, were
      used particularly among older multigravid women. Adverse pregnancy effects were
      not observed in areca nut users compared with non-users. Smoking, but not areca
      nut use, had a dose-related effect on miscarriage. Areca nut use in conjunction
      with smoking reduced the adverse effects of smoking on birth weight, further
      supporting a lack of effect of areca nut. Areca (betel) nut-related adverse
      pregnancy outcomes were not observed in this population, whereas smoking was
      clearly harmful. Differences from previous reports may result from the amount or
      types of areca nut, or quid content, consumed between countries. Smoking, but not
      areca nut, reduction is likely to improve pregnancy outcomes on the Thai-Myanmar
      border.

PMID- 24029402
TI  - Community-based study on knowledge, attitudes and perception of rabies in
      Gelephu, south-central Bhutan.
AB  - Community knowledge, attitudes and practices are important both for prevention of
      human deaths due to rabies and for control of the disease in animals. This study
      was a cross-sectional survey investigating the level of community knowledge as
      well as attitudes and perceptions about rabies in Gelephu, south-central Bhutan,
      a region endemic for rabies. A total of 615 household respondents were
      interviewed, of which 224 (36%) were male and 391 (64%) were female. The majority
      of respondents had a high level of knowledge, attitudes and perception of rabies
      and had a positive attitude towards the prevention and control of rabies.
      Multivariate logistic regression modelling showed that better knowledge of rabies
      was predicted by gender, educational level and dog ownership status of
      respondents, whilst health-seeking behaviour of animal bite injuries was
      predicted by dog ownership status, presence of children in the household and
      occupation of the respondents. The majority of respondents believed that stray
      dogs are a problem in the community and felt that it was important to control the
      dog population in Gelephu. These findings also indicate that there exists a
      knowledge gap about rabies in the community that could be improved by creating an
      awareness education programme.

PMID- 24029403
TI  - Evaluation of a demonstration primary health care project in rural Guatemala: the
      influence of predisposing, enabling and need factors on immunization coverage,
      equitable use of health care services and application of treatment guidelines.
AB  - In high- and low-resource settings, care is often provided inequitably, with more
      and higher-quality services being offered to those who need them less. We
      evaluated the influence of predisposing, enabling and need characteristics on
      immunization coverage and use of health services in a population-based primary
      health care model called the Inclusive Health Model in rural Guatemala. We also
      analyzed providers' application of treatment guidelines for children with
      pneumonia. A longitudinal cohort design was used from 2006 to 2009 to analyze
      data from the model's two demonstration sites. We found a significant positive
      association between families' health risk level and their use of health care
      services, with the model providing more services to those with greater need.
      Services are not provided differentially for those families with a higher or
      lower wealth level or selected sociodemographic characteristics. Distance from a
      clinic is significantly associated with lower service use, but this constraint
      decreases with time. Implementation of treatment guidelines does not vary with
      different provider characteristics. The Inclusive Health Care model's aim of
      offering care equitably to families living in its catchment area is reflected in
      these findings. This study offers an approach and conceptual model for tracking
      equity in service delivery that may be applicable in other settings.

PMID- 24029404
TI  - Diagnostic gap in Bovine viral diarrhea virus serology during the periparturient
      period in cattle.
AB  - Detection of antibodies against Bovine viral diarrhea virus (BVDV) in serum and
      milk by enzyme-linked immunosorbent assay (ELISA) is a crucial part of all
      ongoing national schemes to eradicate this important cattle pathogen. Serum and
      milk are regarded as equally suited for antibody measurement. However, when
      retesting a seropositive cow 1 day after calving, the serum was negative in 6 out
      of 9 different ELISAs. To further investigate this diagnostic gap around
      parturition, pre- and postcalving serum and milk samples of 5 cows were analyzed
      by BVDV antibody ELISA and serum neutralization test (SNT). By ELISA, 3 out of
      the 5 animals showed a diagnostic gap in the serum for up to 12 days around
      calving but all animals remained positive in SNT. In milk, the ELISA was strongly
      positive after birth but antibody levels decreased considerably within the next
      few days. Because of the immunoglobulin G (IgG)1-specific transport of serum
      antibodies into the mammary gland for colostrum production, the IgG subclass
      specificity of the total and the BVDV-specific antibodies were determined.
      Although all 5 animals showed a clear decrease in the total and BVDV-specific
      IgG1 antibody levels at parturition, the precalving IgG1-to-IgG2 ratios of the
      BVDV-specific antibodies were considerably lower in animals that showed the
      diagnostic gap. Results showed that BVDV seropositive cows may become "false"
      negative in several ELISAs in the periparturient period and suggest that the
      occurrence of this diagnostic gap is influenced by the BVDV-specific IgG subclass
      response of the individual animal. 

PMID- 24029405
TI  - Merogonic stages of Theileria cervi in mule deer (Odocoileus hemionus).
AB  - In February 2012, 12 farmed mule deer (Odocoileus hemionus) were moved from a
      facility in southwestern Oklahoma to a facility in southeastern Oklahoma that
      housed 100 farmed white-tailed deer (Odocoileus virginianus). Between the third
      and fifth weeks, 9 of the 12 mule deer had died, 4 of which were submitted for
      necropsy. The deer were heavily infested with Amblyomma americanum (lone star
      ticks). Hematologic data from 1 deer revealed severe anemia, leukocytosis, and
      intraerythrocytic hemoparasites consistent with Theileria spp. Microscopically,
      the liver, lymph nodes, and spleen contained multifocally distributed, enlarged
      monocytic cells whose cytoplasm was replaced by developing meronts in various
      stages of merogony. It appears that, upon arrival, the Theileria cervi-naive mule
      deer became infested with large numbers of Theileria-infected lone star ticks
      leading to massive exposure of the mule deer to sporozoites of the protozoan,
      resulting in an acute hemolytic crisis and fatalities. The merogonic stages of T.
      cervi are also described. The lack of earlier reports of merogony may be due to
      the fact that only a single, short-lived, merogonic cycle follows exposure to
      sporozoites and thus merogonic stages are demonstrable for only a short period.
      Polymerase chain reaction testing of paraffin-embedded tissue yielded a 507-bp
      amplicon sequence that was 100% identical with the sequence of T. cervi
      previously reported from white-tailed deer in Oklahoma and from elk in Wisconsin
      and Indiana. 

PMID- 24029406
TI  - Resolution by recombination: breaking up Solanum pennellii introgressions.
AB  - Quantitative trait locus (QTL) genetics retains an important role in the study of
      biological and agronomic processes; however, its genetic resolution is often
      comparatively low. Community-based strategies are thus required to address this
      issue. Here we detail such a strategy wherein the widely used Solanum pennellii
      introgression lines (ILs) in the genetic background of the cultivated tomato
      (Solanum lycopersicum) are broken up into molecular marker-defined sublines as a
      community resource for map-based cloning. 

PMID- 24029407
TI  - Replica exchange molecular dynamics simulations of an alpha/beta-type small acid
      soluble protein (SASP).
AB  - Small acid soluble proteins (SASPs) of alpha/beta-type play a major role in the
      resistance of spore DNAs to external assaults. It has been found that alpha/beta
      type SASP exhibits intrinsic disorder on isolation, but it acquires a defined
      native state upon binding to DNA. This disorder to order transition is not yet
      understood. Other questions related to the role of the thermodynamics and
      structure of the individual protein in the complex formation remain elusive.
      Characterization of the unbound state of alpha/beta-type SASP in experiments
      could be a challenging problem because of the heterogeneous nature of the
      ensemble. Here, computer simulations can help gain more insights into the unbound
      state of alpha/beta-type SASP. In the present work, by using replica exchange
      molecular dynamics (REMD), we simulated an alpha/beta-type SASP on isolation with
      an implicit solvent. We found that alpha/beta-type SASP undergoes a continuous
      phase transition with a small free energy barrier, a common feature of
      intrinsically disordered proteins (IDPs). Additionally, we detected the presence
      of residual alpha-helical structures at local level and a high degree of
      plasticity in the chain which can contribute to the fast disorder to order
      transition by reducing the fly-casting mechanism. 

PMID- 24029409
TI  - Are conjugated linolenic acid isomers an alternative to conjugated linoleic acid
      isomers in obesity prevention?
AB  - Despite its benefits, conjugated linoleic acid (CLA) may cause side effects after
      long-term administration. Because of this and the controversial efficacy of CLA
      in humans, alternative biomolecules that may be used as functional ingredients
      have been studied in recent years. Thus, conjugated linolenic acid (CLNA) has
      been reported to be a potential anti-obesity molecule which may have additional
      positive effects related to obesity. According to the results reported in
      obesity, CLNA needs to be given at higher doses than CLA to be effective.
      However, because of the few studies conducted so far, it is still difficult to
      reach clear conclusions about the potential use of these CLNAs in obesity and its
      related changes (insulin resistance, dyslipidemia, or inflammation).

PMID- 24029408
TI  - First-in-human evaluation of genetically attenuated Plasmodium falciparum
      sporozoites administered by bite of Anopheles mosquitoes to adult volunteers.
AB  - BACKGROUND: Immunization with genetically engineered, attenuated malaria
      parasites (GAP) that arrest during liver infection confers sterile protection in
      mouse malaria models. A first generation Plasmodium falciparum GAP (Pf p52(
      )/p36(-) GAP) was previously generated by deletion of two pre-erythrocytic stage
      expressed genes (P52 and P36) in the NF54 strain. METHODS: A first-in-human,
      proof-of-concept, safety and immunogenicity clinical trial in six human
      volunteers was conducted. Exposure consisted of delivery of Pf p52(-)/p36(-) GAP
      sporozoites via infected Anopheles mosquito bite with a five-bite/volunteer
      exposure followed by an approximately 200-bite exposure/volunteer one month
      later. RESULTS: The exposures were well tolerated with mild to moderate local and
      systemic reactions. All volunteers remained blood stage negative after low dose
      exposure. Five volunteers remained blood stage negative after high dose exposure.
      One volunteer developed peripheral parasitemia twelve days after high dose
      exposure. Together the findings indicate that Pf p52(-)/p36(-) GAP was severely
      but not completely attenuated. All six volunteers developed antibodies to CSP.
      Furthermore, IFN-gamma responses to whole sporozoites and multiple antigens were
      elicited in 5 of 6 volunteers, with both CD4 and CD8 cell cytokine production
      detected. CONCLUSION: Severe attenuation and favorable immune responses following
      administration of a first generation Pf p52(-)/p36(-) GAP suggests that further
      development of live-attenuated strains using genetic engineering should be
      pursued.

PMID- 24029410
TI  - Are antidepressants effective in quality of life improvement among children and
      adolescents? A systematic review.
AB  - There is some evidence indicating that psychotropic medications might lead to
      health-related quality of life (QOL) improvements among children and adolescents
      with psychiatric disorders. The aim of this systematic review is to assess
      evidence regarding whether antidepressant treatment improves QOL among children
      and adolescents with depressive or anxiety disorders. A comprehensive search
      resulted in 5 clinical trials to be included in this review: 4 trials with major
      depressive disorder (MDD) and 1 trial with social anxiety disorder (SAD). In one
      MDD trial, fluoxetine combined with cognitive behavior therapy (CBT)
      significantly improved QOL compared to fluoxetine or CBT alone (effect sizes were
      0.53 and 0.69, respectively). In 2 combined trials, sertraline alone
      significantly improved QOL among adolescents with MDD (effect size was 0.29), but
      not among children with MDD. Essentially, it was observed that antidepressants in
      these trials had minor positive effects on QOL improvement, which were lower than
      their potential to improve depressive symptoms. Although fluoxetine with CBT or
      sertraline monotherapy were shown to have some potential to improve QOL, this
      systematic review found inconclusive evidence that antidepressant treatments
      improve QOL among children and adolescents with depressive or anxiety disorders.
      More research is required, considering that QOL is currently under-evaluated in
      clinical trials with antidepressants among children and adolescents and available
      trials have limited methodological quality when reporting QOL data. 

PMID- 24029411
TI  - Maintenance therapy for acne vulgaris: efficacy of a 12-month treatment with
      adapalene-benzoyl peroxide after oral isotretinoin and a review of the
      literature.
AB  - BACKGROUND: The correct therapeutic management of acne should include a
      maintenance therapy with topical retinoids to prevent recurrences after
      discontinuing a successful treatment. OBJECTIVE: To investigate the efficacy of a
      12-month maintenance treatment with adapalene 0.1% and benzoyl peroxide (BPO)
      2.5% fixed combination gel to control acne relapse after treatment with oral
      isotretinoin (OI). METHODS: The study consisted of 2 phases, namely an active
      treatment phase (AP) and a maintenance phase (MP). In the AP, 70 consecutive
      patients with moderate to severe acne were treated with OI until acne remission.
      Then, patients entered the MP and were treated with adapalene-BPO fixed
      combination once daily for 12 months. The primary efficacy parameter was the
      relapse rate during MP. RESULTS: Sixty-eight patients completed the study.
      Relapse occurred in 2 patients (2.94%). CONCLUSIONS: Comparing our findings with
      published data, the association of a topical retinoid and BPO seems to provide
      favorable evidence for this combination as maintenance therapy.

PMID- 24029412
TI  - Cognitive patterns in relation to biomarkers of cerebrovascular disease and
      vascular risk factors.
AB  - BACKGROUND: Risk factors for vascular cognitive impairment (VCI) are the same as
      traditional risk factors for cerebrovascular disease (CVD). Early identification
      of subjects at higher risk of VCI is important for the development of effective
      preventive strategies. In addition to traditional vascular risk factors (VRF),
      circulating biomarkers have emerged as potential tools for early diagnoses, as
      they could provide in vivo measures of the underlying pathophysiology. While VRF
      have been consistently linked to a VCI profile (i.e., deficits in executive
      functions and processing speed), the cognitive correlates of CVD biomarkers
      remain unclear. In this population-based study, the aim was to study and compare
      cognitive patterns in relation to VRF and circulating biomarkers of CVD. METHODS:
      The Barcelona-AsIA Neuropsychology Study included 747 subjects older than 50,
      without a prior history of stroke or coronary disease and with a moderate to high
      vascular risk (mean age, 66 years; 34.1% women). Three cognitive domains were
      derived from factoral analysis: visuospatial skills/speed, verbal memory and
      verbal fluency. Multiple linear regression was used to assess relationships
      between cognitive performance (multiple domains) and a panel of circulating
      biomarkers, including indicators of inflammation, C-reactive protein (CRP) and
      resistin, endothelial dysfunction, asymmetric dimethylarginine (ADMA),
      thrombosis, plasminogen activator inhibitor 1 (PAI-1), as well as traditional
      VRF, metabolic syndrome and insulin resistance (homeostatic model assessment for
      insulin resistance index). Analyses were adjusted for age, gender, years of
      education and depressive symptoms. RESULTS: Traditional VRF were related to lower
      performance in verbal fluency, insulin resistance accounted for lower performance
      in visuospatial skills/speed and the metabolic syndrome predicted lower
      performance in both cognitive domains. From the biomarkers of CVD, CRP was
      negatively related to verbal fluency performance and increasing ADMA levels were
      associated with lower performance in verbal memory. Resistin and PAI-1 did not
      relate to cognitive function performance. CONCLUSION: Vascular risk factors, and
      markers of inflammation and endothelial dysfunction predicted lower performance
      in several cognitive domains. Specifically, cognitive functions associated with
      CRP are typically affected in VCI and overlap those related to VRF. ADMA
      indicated a dissociation in the cognitive profile involving verbal memory. These
      findings suggest that inflammation and endothelial dysfunction might play a role
      in the predementia cognitive impairment stages.

PMID- 24029413
TI  - Hierarchical visible-light-response Ag/AgCl@TiO2 plasmonic photocatalysts for
      organic dye degradation.
AB  - A plasmonic photocatalyst of Ag/AgCl@TiO2 nanoparticles (NPs) was directly
      prepared by a one-step sonochemical method. Both Ag NPs and AgCl were co
      deposited on TiO2 NPs to form Ag@TiO2 and Ag/AgCl@TiO2 using the method. Due to
      the localized surface plasmonic effects of Ag NPs, the visible-light absorbance
      of the Ag/AgCl@TiO2 photocatalyst was dramatically increased and the
      photocatalytic activity to decompose Rhodamine B was much improved under visible
      light. In addition, due to the advantages of the sonochemical approach, only a
      very small amount of Ag is required to obtain a high photocatalytic activity in
      the plasmonic catalyst. The mechanism for the enhancement of the visible-light
      driven photocatalytic activities was also analyzed. 

PMID- 24029414
TI  - National study of chronic disease self-management: six-month outcome findings.
AB  - OBJECTIVE: To investigate how the Chronic Disease Self-Management Program (CDSMP)
      changes health outcomes, lifestyle behaviors, and health care service utilization
      over a 6 month period. METHOD: The participants were 1,170 adults enrolled in the
      National Study of CDSMP in 2010-2012 (M age=65.4 years). Six-month assessments
      were available for 903 participants. Linear mixed models and generalized linear
      mixed models were used to assess the changes between baseline and 6-month
      assessment for primary and secondary outcomes among CDSMP participants. RESULTS:
      Social/role activities limitations, depression, and communication with physicians
      improved significantly from baseline to 6-month follow-up. Study participants
      reported significant improvements in more physical activity and less emergency
      room (ER) visits and hospitalization during that period. DISCUSSION: Nationally,
      CDSMP not only improves health outcomes and lifestyle behaviors but also
      decreases costly ER visits and hospitalization. Geriatricians and other primary
      care providers should be encouraged to refer patients with chronic conditions to
      such self-management programs.

PMID- 24029415
TI  - Identification of a strong contamination source for graphene in vacuum systems.
AB  - To minimize parasitic doping effects caused by uncontrolled material adsorption,
      graphene is often investigated under vacuum. Here we report an entirely
      unexpected phenomenon occurring in vacuum systems, namely strong n-doping of
      graphene due to chemical species generated by common ion high-vacuum gauges. The
      effect-reversible upon exposing graphene to air-is significant, as doping rates
      can largely exceed 10(12) cm(-2) h(-1), depending on pressure and the relative
      position of the gauge and the graphene device. It is important to be aware of
      this phenomenon, as its basic manifestation can be mistakenly interpreted as
      vacuum-induced desorption of p-dopants.

PMID- 24029416
TI  - The quality of life in Chinese patients with systemic lupus erythematosus is
      associated with disease activity and psychiatric disorders: a path analysis.
AB  - OBJECTIVES: To identify the socioeconomic status, disease activity and
      psychiatric disorders that contribute to the health-related quality of life
      (HRQOL) in systemic lupus erythematosus (SLE) patients. METHODS: Data were
      collected from 170 SLE patients and 210 healthy individuals. All of the patients
      fulfilled the criteria for the classification of SLE and underwent disease
      activity assessment according to the SLE disease activity index (SLEDAI). Self
      rated scales for anxiety (SAS) and depression (SDS) were used to evaluate the
      levels of anxiety and depression. The patients' general health status was
      measured using the Short Form (SF)-36 questionnaire. To provide greater clarity
      regarding the determinants of HRQOL, path analysis was used to explore the
      relationships between the various predictors and the health-related quality of
      life (HRQoL). RESULTS: SLE patients who have depression and anxiety are more
      likely to have a lower quality of life compared to those who are not depressed
      (r=-0.735, p<0.01; r=-0.684, p<0.01). All of the variables were significantly
      correlated with depression except age, gender and marital status. Education was
      negatively correlated with disease activity (r=-0.272, p<0.05) and anxiety (r=
      0.312, p<0.01). Disease activity was positively correlated with anxiety (r=0.198,
      p<0.05). In addition, work status also correlated with anxiety (r=-0.294,
      p<0.01). A path-analytic models analysis suggested that the main influencing
      factors of HRQoL are the following: depression, anxiety, education level,
      income/family, disease activity, age, and work status. A chi2 test (chi215=17.71,
      p=0.28>0.05) indicated that the path analysis model had an adequate goodness of
      fit value. Depression (beta=-0.616, p<0.05) contributed the most to HRQOL.
      Depression, anxiety and disease activity contributed to HRQoL both directly and
      indirectly through other factors. Socioeconomic factors such as education,
      income/family and work status, however, did not contribute directly to HRQoL.
      CONCLUSIONS: HRQoL in SLE is influenced by disease activity and psychiatric
      disorders. Socioeconomic status has no direct influence on the quality of life of
      lupus patients, while disease activity has a direct impact on the quality of
      life. Anxiety and depression were significant predictors of poor HRQoL.
      Understanding how these factors are inter-related may help clinicians focus their
      assessments and develop strategies to improve the HRQoL of lupus patients.

PMID- 24029417
TI  - Preclinical evaluation of a new liposomal formulation of cisplatin, lipoplatin,
      to treat cisplatin-resistant cervical cancer.
AB  - OBJECTIVE: Cisplatin-based chemotherapy has been shown to improve survival in
      cervical cancer; however, treatment is associated with tumor resistance and
      significant toxicity. Lipoplatin is a new liposomal formulation of cisplatin,
      developed to reduce cisplatin toxicity, to improve drug accumulation at tumor
      sites and to overcome drug resistance. The aim of this study is to analyze the
      antitumoral activity of lipoplatin against cisplatin-resistant cervical cancer
      cells and to investigate its mechanism of action. METHODS: The activity and
      mechanism of action of lipoplatin were studied in the ME-180 cervical cancer cell
      line and its cisplatin-resistant clone R-ME-180 and HeLa cells using cell
      proliferation assays, flow cytometry, ELISA assay, cell migration, spheroids and
      tumor xenograft. RESULTS: We demonstrated that lipoplatin exhibited a potent
      antitumoral activity on HeLa, ME-180 cells and its cisplatin-resistant clone R-ME
      180. Lipoplatin inhibited cell proliferation in a dose-dependent manner and was
      more active than the reference drug cisplatin in R-ME-180 cells and induced
      apoptosis, as evaluated by Annexin-V staining and DNA fragmentation, caspases 9
      and 3 activation, Bcl-2, and Bcl-xL down-regulation, but Bax up-regulation
      inhibited thioredoxin reductase (TrxR) enzymatic activity and increased reactive
      oxygen species (ROS) accumulation; reduced EGFR expression and inhibited both
      migration and invasion. R-ME-180, but not ME-180 cells, generated three
      dimensional (3D)-multicellular spheroids expressing the cancer stem cell marker
      ALDH. The ability of R-ME-180 cells to form spheroids in vitro and tumors in nude
      mice was also remarkably decreased by lipoplatin. CONCLUSIONS: Overall, our
      results suggest that lipoplatin has potential for the treatment of cisplatin
      resistant cervical cancer.

PMID- 24029418
TI  - Clinical outcomes following 3D image-guided brachytherapy for vaginal recurrence
      of endometrial cancer.
AB  - PURPOSE: To evaluate clinical outcomes for women with recurrent endometrial
      cancer treated with 3D image-guided brachytherapy METHODS AND MATERIALS: 44
      women, of whom 13 had received prior RT, received salvage RT for vaginal
      recurrence from 9/03 to 8/11. HDR or LDR interstitial brachytherapy was performed
      under MR or CT guidance in 35 patients (80%); 9 (20%) had CT-guided HDR cylinder
      brachytherapy. The median cumulative dose in EQD2 was 75.5 Gy. Actuarial
      estimates of local failure (LF), disease-free (DFS) and overall survival (OS)
      were calculated by Kaplan-Meier. RESULTS: Histologic subtypes were endometrioid
      (EAC, 33), papillary serous/clear cell (UPSC/CC, 5) and carcinosarcoma (CS, 6).
      The 2-year DFS/OS rates were 75%/89% for EAC and 11%/24% for UPSC/CC/CS (both
      p<0.01). On MVA, high tumor grade was associated with recurrence (HR 3.2 for
      grade 2, 9.6 for grade 3, p<0.01). The LF rate at 2 years was 4% for patients
      without versus 39% for those with prior RT (p=0.1). Patients who had prior RT
      received lower cumulative doses at recurrence (66.5 Gy vs. 74.4 Gy, p<0.01). The
      2-year DFS/OS rates with and without prior RT were 26%/55% and 72%/80% (both
      p=0.1). Four patients (9%) experienced grade 3 late toxicity, including 3 of 13
      (23%) in the re-irradiation setting and 1 of 31 (3%) with no prior radiotherapy.
      DISCUSSION: 3D image-guided brachytherapy results in excellent local control for
      women with recurrent endometrial cancer, particularly with cumulative EQD2 doses
      greater than 70 Gy. Successful salvage of vaginal recurrence is related to tumor
      grade and histologic subtype.

PMID- 24029419
TI  - Stress granules and cell signaling: more than just a passing phase?
AB  - Stress granules (SGs) contain translationally-stalled mRNAs, associated
      preinitiation factors, and specific RNA-binding proteins. In addition, many
      signaling proteins are recruited to SGs and/or influence their assembly, which is
      transient, lasting only until the cells adapt to stress or die. Beyond their role
      as mRNA triage centers, we posit that SGs constitute RNA-centric signaling hubs
      analogous to classical multiprotein signaling domains such as transmembrane
      receptor complexes. As signaling centers, SG formation communicates a 'state of
      emergency', and their transient existence alters multiple signaling pathways by
      intercepting and sequestering signaling components. SG assembly and downstream
      signaling functions may require a cytosolic phase transition facilitated by
      intrinsically disordered, aggregation-prone protein regions shared by RNA-binding
      and signaling proteins. 

PMID- 24029421
TI  - Prediction of outcomes in crescentic IgA nephropathy in a multicenter cohort
      study.
AB  - Crescentic IgA nephropathy (IgAN), defined as >50% crescentic glomeruli on kidney
      biopsy, is one of the most common causes of rapidly progressive GN. However, few
      studies have characterized this condition. To identify risk factors and develop a
      prediction model, we assessed data from patients >= 14 years old with crescentic
      IgAN who were followed >= 12 months. The discovery cohort comprised 52 patients
      from one kidney center, and the validation cohort comprised 61 patients from
      multiple centers. At biopsy, the mean serum creatinine (SCr) level +/- SD was 4.3
      +/- 3.4 mg/dl, and the mean percentage of crescents was 66.4%+/- 15.8%. The
      kidney survival rates at years 1, 3, and 5 after biopsy were 57.4%+/- 4.7%,
      45.8%+/- 5.1%, and 30.4%+/- 6.6%, respectively. Multivariate Cox regression
      revealed initial SCr as the only independent risk factor for ESRD (hazard ratio
      [HR], 1.32; 95% confidence interval [CI], 1.10 to 1.57; P=0.002). Notably, the
      percentage of crescents did not associate independently with ESRD. Logistic
      regression showed that the risk of ESRD at 1 year after biopsy increased rapidly
      at SCr>2.7 mg/dl and reached 90% at SCr>6.8 mg/dl (specificity=98.5%,
      sensitivity=64.6% for combined cohorts). In both cohorts, patients with SCr>6.8
      mg/dl were less likely to recover from dialysis. Analyses in additional cohorts
      revealed a similar association between initial SCr and ESRD in patients with
      antiglomerular basement membrane disease but not ANCA-associated systemic
      vasculitis. In conclusion, crescentic IgAN has a poor prognosis, and initial SCr
      concentration may predict kidney failure in patients with this disease.

PMID- 24029422
TI  - Downregulation of microRNA-30 facilitates podocyte injury and is prevented by
      glucocorticoids.
AB  - MicroRNAs (miRNAs) are essential for podocyte homeostasis, and the miR-30 family
      may be responsible for this action. However, the exact roles and clinical
      relevance of miR-30s remain unknown. In this study, we examined the expression of
      the miR-30 family in the podocytes of patients with FSGS and found that all
      members are downregulated. Treating cultured human podocytes with TGF-beta, LPS,
      or puromycin aminonucleoside (PAN) also downregulated the miR-30 family. Podocyte
      cytoskeletal damage and apoptosis caused by treatment with TGF-beta or PAN were
      ameliorated by exogenous miR-30 expression and aggravated by miR-30 knockdown.
      Moreover, we found that miR-30s exert their protective roles by direct inhibition
      of Notch1 and p53, which mediate podocyte injury. In rats, treatment with PAN
      substantially downregulated podocyte miR-30s and induced proteinuria and podocyte
      injury; however, transfer of exogenous miR-30a to podocytes of PAN-treated rats
      ameliorated proteinuria and podocyte injury and reduced Notch1 activation.
      Finally, we demonstrated that glucocorticoid treatment maintains miR-30
      expression in cultured podocytes treated with TGF-beta, LPS, or PAN and in the
      podocytes of PAN-treated rats. Glucocorticoid-sustained miR-30 expression
      associated with reduced Notch1 activation and alleviated podocyte damage. Taken
      together, these findings demonstrate that miR-30s protect podocytes by targeting
      Notch1 and p53 and that the loss of miR-30s facilitates podocyte injury. In
      addition, sustained miR-30 expression may be a novel mechanism underlying the
      therapeutic effectiveness of glucocorticoids in treating podocytopathy. 

PMID- 24029423
TI  - Patient-specific prediction of ESRD after liver transplantation.
AB  - Incident ESRD after liver transplantation (LT) is associated with high post
      transplant mortality. We constructed and validated a continuous renal risk index
      (RRI) to predict post-LT ESRD. Data for 43,514 adult recipients of deceased donor
      LT alone (February 28, 2002 to December 31, 2010) were linked from the Scientific
      Registry of Transplant Recipients and the Centers for Medicare and Medicaid
      Services ESRD Program. An adjusted Cox regression model of time to post-LT ESRD
      was fitted, and the resulting equation was used to calculate an RRI for each LT
      recipient. The RRI included 14 recipient factors: age, African-American race,
      hepatitis C, cholestatic disease, body mass index >= 35, pre-LT diabetes, ln
      creatinine for recipients not on dialysis, ln albumin, ln bilirubin, serum
      sodium<134 mEq/L, status-1, previous LT, transjugular intrahepatic portosystemic
      shunt, and acute dialysis at LT. This RRI was validated and had a C statistic of
      0.76 (95% confidence interval, 0.75 to 0.78). Higher RRI associated significantly
      with higher 5-year cumulative incidence of ESRD and post-transplant mortality. In
      conclusion, the RRI constructed in this study quantifies the risk of post-LT ESRD
      and is applicable to all LT alone recipients. This new validated measure may
      serve as an important prognostic tool in ameliorating post-LT ESRD risk and
      improve survival by informing post-LT patient management strategies.

PMID- 24029424
TI  - Proteome-wide measurement of protein half-lives and translation rates in
      vasopressin-sensitive collecting duct cells.
AB  - Vasopressin regulates water excretion, in part, by controlling the abundances of
      the water channel aquaporin-2 (AQP2) protein and regulatory proteins in the renal
      collecting duct. To determine whether vasopressin-induced alterations in protein
      abundance result from modulation of protein production, protein degradation, or
      both, we used protein mass spectrometry with dynamic stable isotope labeling in
      cell culture to achieve a proteome-wide determination of protein half-lives and
      relative translation rates in mpkCCD cells. Measurements were made at steady
      state in the absence or presence of the vasopressin analog, desmopressin (dDAVP).
      Desmopressin altered the translation rate rather than the stability of most
      responding proteins, but it significantly increased both the translation rate and
      the half-life of AQP2. In addition, proteins associated with vasopressin action,
      including Mal2, Akap12, gelsolin, myosin light chain kinase, annexin-2, and
      Hsp70, manifested altered translation rates. Interestingly, desmopressin
      increased the translation of seven glutathione S-transferase proteins and
      enhanced protein S-glutathionylation, uncovering a previously unexplored
      vasopressin-induced post-translational modification. Additional bioinformatic
      analysis of the mpkCCD proteome indicated a correlation between protein function
      and protein half-life. In particular, processes that are rapidly regulated, such
      as transcription, endocytosis, cell cycle regulation, and ubiquitylation are
      associated with proteins with especially short half-lives. These data extend our
      understanding of the mechanisms underlying vasopressin signaling and provide a
      broad resource for additional investigation of collecting duct function
      (http://helixweb.nih.gov/ESBL/Database/ProteinHalfLives/index.html). 

PMID- 24029425
TI  - Diabetic nephropathy: is ESRD its only heritable phenotype?

PMID- 24029420
TI  - Common variants in Mendelian kidney disease genes and their association with
      renal function.
AB  - Many common genetic variants identified by genome-wide association studies for
      complex traits map to genes previously linked to rare inherited Mendelian
      disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs)
      in genes responsible for Mendelian diseases with kidney phenotypes has not been
      performed. We thus developed a comprehensive database of genes for Mendelian
      kidney conditions and evaluated the association between common genetic variants
      within these genes and kidney function in the general population. Using the
      Online Mendelian Inheritance in Man database, we identified 731 unique disease
      entries related to specific renal search terms and confirmed a kidney phenotype
      in 218 of these entries, corresponding to mutations in 258 genes. We interrogated
      common SNPs (minor allele frequency >5%) within these genes for association with
      the estimated GFR in 74,354 European-ancestry participants from the CKDGen
      Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at
      TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in
      a stage 2 meta-analysis performed in 56,246 additional independent individuals,
      indicating that these common SNPs are not associated with estimated GFR. The
      effect of less common or rare variants in these genes on kidney function in the
      general population and disease-specific cohorts requires further research. 

PMID- 24029426
TI  - Long-term outcomes in idiopathic membranous nephropathy using a restrictive
      treatment strategy.
AB  - Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines
      recommend limiting the use of immunosuppressive drugs in idiopathic membranous
      nephropathy to patients at the highest risk of kidney failure. However,
      recommendations are based on natural history rather than direct assessment of a
      restrictive treatment strategy. Here, we describe the long-term outcomes of
      treating a large cohort of patients with idiopathic membranous nephropathy
      according to a restrictive treatment policy. We analyzed data for 254 patients
      who visited our outpatient clinic between 1995 and 2009. All patients were
      treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor
      blockers. Immunosuppressive therapy was recommended in cases of deteriorating
      renal function or untreatable nephrotic syndrome. Primary outcomes for the
      present study were renal replacement therapy and death. Secondary outcomes
      included adverse events during follow-up and remission of proteinuria. In total,
      124 patients (49%) received immunosuppressive therapy, which predominantly
      consisted of cyclophosphamide combined with steroids. Ten-year cumulative
      incidence rates were 3% for renal replacement therapy and 10% for death. Partial
      remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively;
      complete remission rates were 5%, 24%, and 38% at 1, 3, and 5 years,
      respectively. A serious adverse event occurred in 23% of all patients. The most
      notable complications were infections (17%), leukopenia (18%), cardiovascular
      events (13%), and malignancies (8%). In conclusion, the use of a restrictive
      treatment strategy in this cohort of patients with idiopathic membranous
      nephropathy yielded favorable outcomes while limiting the number of patients
      exposed to toxic drugs. These results support current KDIGO guidelines. 

PMID- 24029428
TI  - Comprehensive genetic analysis of complement and coagulation genes in atypical
      hemolytic uremic syndrome.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy caused
      by uncontrolled activation of the alternative pathway of complement at the cell
      surface level that leads to microangiopathic hemolytic anemia, thrombocytopenia,
      and acute kidney failure. In approximately one half of affected patients,
      pathogenic loss-of-function variants in regulators of complement or gain-of
      function variants in effectors of complement are identified, clearly implicating
      complement in aHUS. However, there are strong lines of evidence supporting the
      presence of additional genetic contributions to this disease. To identify novel
      aHUS-associated genes, we completed a comprehensive screen of the complement and
      coagulation pathways in 36 patients with sporadic aHUS using targeted genomic
      enrichment and massively parallel sequencing. After variant calling, quality
      control, and hard filtering, we identified 84 reported or novel nonsynonymous
      variants, 22 of which have been previously associated with disease. Using
      computational prediction methods, 20 of the remaining 62 variants were predicted
      to be deleterious. Consistent with published data, nearly one half of these 42
      variants (19; 45%) were found in genes implicated in the pathogenesis of aHUS.
      Several genes in the coagulation pathway were also identified as important in the
      pathogenesis of aHUS. PLG, in particular, carried more pathogenic variants than
      any other coagulation gene, including three known plasminogen deficiency
      mutations and a predicted pathogenic variant. These data suggest that mutation
      screening in patients with aHUS should be broadened to include genes in the
      coagulation pathway. 

PMID- 24029429
TI  - Individualized anemia management reduces hemoglobin variability in hemodialysis
      patients.
AB  - One-size-fits-all protocol-based approaches to anemia management with
      erythropoiesis-stimulating agents (ESAs) may result in undesired patterns of
      hemoglobin variability. In this single-center, double-blind, randomized
      controlled trial, we tested the hypothesis that individualized dosing of ESA
      improves hemoglobin variability over a standard population-based approach. We
      enrolled 62 hemodialysis patients and followed them over a 12-month period.
      Patients were randomly assigned to receive ESA doses guided by the Smart Anemia
      Manager algorithm (treatment) or by a standard protocol (control). Dose
      recommendations, performed on a monthly basis, were validated by an expert
      physician anemia manager. The primary outcome was the percentage of hemoglobin
      concentrations between 10 and 12 g/dl over the follow-up period. A total of 258
      of 356 (72.5%) hemoglobin concentrations were between 10 and 12 g/dl in the
      treatment group, compared with 208 of 336 (61.9%) in the control group; 42
      (11.8%) hemoglobin concentrations were <10 g/dl in the treatment group compared
      with 88 (24.7%) in the control group; and 56 (15.7%) hemoglobin concentrations
      were >12 g/dl in the treatment group compared with 46 (13.4%) in the control
      group. The median ESA dosage per patient was 2000 IU/wk in both groups. Five
      participants received 6 transfusions (21 U) in the treatment group, compared with
      8 participants and 13 transfusions (31 U) in the control group. These results
      suggest that individualized ESA dosing decreases total hemoglobin variability
      compared with a population protocol-based approach. As hemoglobin levels are
      declining in hemodialysis patients, decreasing hemoglobin variability may help
      reduce the risk of transfusions in this population. 

PMID- 24029430
TI  - The WHI ten year's later: an epidemiologist's view.
AB  - The Women's Health Initiative (WHI) clinical trials generated definitive answers
      to the specific questions they were designed to answer. Menopausal hormone
      therapy in the form of oral conjugated equine estrogens (CEE) alone or CEE plus
      medroxyprogesterone acetate (CEE+MPA) should not be used for primary prevention
      of chronic diseases among postmenopausal women because the risks outweigh the
      benefits. Before the WHI clinical trials were stopped early and those results
      were announced, there was a general, although not universal, consensus in the
      scientific literature and public at large that menopausal hormone therapy's
      benefits outweighed its risks. In the ten years since the surprising early
      termination of those two WHI clinical trials, substantial discussion, critique,
      reanalysis, and opinion has been offered to reconcile the differences between the
      WHI clinical trial results and a diverse set of a priori and a posteriori
      expectations. Some of that assessment has focused on epidemiologic studies, which
      had provided much of the data on which the original decision to launch the WHI
      trials was based. This review discusses a number of potential lessons that
      current and future epidemiology could take from the WHI. Epidemiologic
      observational studies should more often emulate the big-picture perspective of
      randomized clinical trials. Even apparently conflicting epidemiologic study
      observations and clinical trial results may have similar underlying data.
      Creative use of both intervention and observational study designs and data, for
      both menopausal hormone therapy and other important exposures, is essential to
      generating the research, clinical, and translational findings that advance public
      health. This article is part of a Special Issue entitled 'Menopause'. 

PMID- 24029431
TI  - Validity of the Patient Health Questionnaire (PHQ)-9 and PHQ-2 in general
      internal medicine primary care at a Japanese rural hospital: a cross-sectional
      study.
AB  - OBJECTIVE: Two depression screening tools, Patient Health Questionnaire (PHQ)-9
      and PHQ-2, have not had their validity examined in general internal medicine
      settings in Japan. We examined the validity of these screening tools. METHODS: A
      total of 598 outpatients of an internal medicine clinic in a rural general
      hospital were enrolled consecutively and stratified by PHQ-9 score. Seventy-five
      patients randomly selected and 29 patients whose results from the PHQ-9 were
      considered to be positive for depressive disorder were then interviewed with a
      semistructured interview, the Mini International Neuropsychiatric Interview. We
      calculated diagnostic accuracy of the PHQ-9 and PHQ-2 to detect major depression
      and that of the suicidality item of the PHQ-9 to detect suicidality using
      sampling weights with multiple imputations. RESULTS: Sensitivity and specificity
      for depression were 0.86 and 0.85, respectively, for the PHQ-9 with cutoff points
      of 4/5, and 0.77 and 0.95, respectively, for the PHQ-2 with cutoff points of 2/3.
      Sensitivity and specificity of the suicidality item of the PHQ-9 were 0.70 and
      0.97, respectively. CONCLUSION: In internal medicine clinics in Japanese rural
      hospitals, the PHQ-2 with an optimal cutoff point for each setting plus the
      suicidality item of the PHQ-9 can be recommended to detect depression without
      missing suicidality.

PMID- 24029432
TI  - Tigecycline in the management of osteomyelitis: a case series from the bone and
      joint infection (BAJIO) database.
AB  - Tigecycline is approved for cutaneous infections, intra-abdominal infections, and
      community-acquired pneumonia. However, pharmacokinetic data suggest therapeutic
      concentrations in additional sites, such as bone, despite exiguous clinical data
      supporting such use. Thus, the objective of this study was to analyze patients
      with osteomyelitis treated with tigecycline to ascertain its utility in this
      malady. Our database of osteomyelitis patients was surveyed for instances treated
      with tigecycline. Cases were evaluated in terms of adverse events and clinical
      success. Nineteen patients received tigecycline for osteomyelitis. Thirteen met
      criteria for evaluation of the primary endpoint of clinical success. The most
      common dose employed was 50 mg twice daily. Adverse events, however, were not
      statistically more likely with 100 mg administered once daily. Eleven patients
      (85%) achieved clinical success. Thus, congruent with pharmacokinetic data,
      tigecycline appeared efficacious for osteomyelitis in the majority of patients
      who received it. Adverse events were not correlated with dosing strategy. 

PMID- 24029433
TI  - In vitro efficacy of fosfomycin-based combinations against clinical vancomycin
      resistant Enterococcus isolates.
AB  - Vancomycin-resistant (VR) enterococci (VRE) are increasingly important nosocomial
      pathogens, commonly causing catheter-related urinary tract infections or vascular
      catheter-related bloodstream infections. In this study, 10 Enterococcus faecium
      and 9 Enterococcus faecalis different pulsed-field gel electrophoresis genome
      type VR clinical isolates were detected. The potential role of fosfomycin-based
      combination regimens for biofilm-related VRE infection is in vitro evaluated.
      Anti-VRE activities of fosfomycin, ampicillin, linezolid, minocycline,
      rifampicin, tigecycline, teicoplanin, vancomycin alone, or fosfomycin-based
      combinations were studied by time-kill method and a biofilm model. Of the
      fosfomycin-based combinations, a synergistic effect was particularly noted for
      teicoplanin against 89% of the VR E. faecalis isolates. In a biofilm model, only
      linezolid alone was able to reduce the bacterial loads, and the use of fosfomycin
      based combinations, excluding rifampicin (40%), failed to enhance antibacterial
      activity against VR E. faecium. For E. faecalis, an inhibitory effect was evident
      using ampicillin alone or fosfomycin plus rifampicin (100%), tigecycline (56%),
      or teicoplanin (44%). However, an antagonistic effect was found for ampicillin
      plus fosfomycin against 2 of 3 of the VR E. faecalis isolates. The antibacterial
      activities of the drugs tested against VRE in vitro varied by species. Ampicillin
      exhibited potential activity against planktonic- and biofilm-embedded VR E.
      faecalis. Fosfomycin-based combinations may have enhanced antibacterial effects
      against VRE even in the biofilm model, and this observation warrants further
      clinical studies. 

PMID- 24029434
TI  - Characteristics of co-infections by HCV and HBV among Brazilian patients infected
      by HIV-1 and/or HTLV-1.
AB  - BACKGROUND: The human retroviruses HIV-1 and HTLV-1 share the routes of infection
      with hepatitis viruses B and C. Co-infection by these agents are a common event,
      but we have scarce knowledge on co-infection by two or more of these agents.
      OBJECTIVE: To evaluate the characteristics and risk factors for co-infections by
      HBV and HCV in patients infected by HIV-1 or/and HTLV-1, in Salvador, Brazil.
      METHODS: In a case-control study we evaluated patients followed in the AIDS and
      HTLV clinics of Federal University of Bahia Hospital. Clinical and
      epidemiological characteristics were reviewed, and patients were tested for the
      presence of serological markers of HBV and HCV infections. HCV-infected patients
      were tested by PCR to evaluate the presence of viremia. RESULTS: A total of 200
      HIV-1, 213 HTLV-1-infected, and 38 HIV-HTLV-co-infected individuals were
      included. HIV-infected patients were more likely to have had more sexual partners
      in the lifetime than other patients' groups. HIV-HTLV-co-infected subjects were
      predominantly male. Patients infected by HTLV or co-infected had a significantly
      higher frequency of previous syphilis or gonorrhea, while HIV infection was
      mainly associated with HPV infection. Co-infection was significantly associated
      to intravenous drug use (IVDU). HBV and/or HCV markers were more frequently found
      among co-infected patients. HBV markers were more frequently detected among HIV
      infected patients, while HCV was clearly associated with IVDU across all groups.
      AgHBs was strongly associated with co-infection by HIV-HTLV (OR=22.03, 95% CI:
      2.69-469.7), as well as confirmed HCV infection (p=0.001). Concomitant HCV and
      HBV infection was also associated with retroviral co-infection. Patients infected
      by HTLV-1 had a lower chance of detectable HCV viremia (OR=0.04, 95% CI: 0.002
      0.85). CONCLUSIONS: Infection by HCV and/or HBV is frequent among patients
      presenting retroviral infection, but risk factors and prevalence for each
      infection are distinct for each agent. Retroviral co-infection increases the risk
      of a positive AgHBs, but HTLV-1 infection seems to increase the likelihood of HCV
      spontaneous clearance.

PMID- 24029435
TI  - Incidence rate of modifying or discontinuing first combined antiretroviral
      therapy regimen due to toxicity during the first year of treatment stratified by
      age.
AB  - Toxicity is the most frequently reported reason for modifying or discontinuing
      the first combined antiretroviral therapy regimens, and it can cause significant
      morbidity, poor quality of life and also can be an important barrier to
      adherence, ultimately resulting in treatment failure and viral resistance.
      Elderly patients with HIV/AIDS (>= 50 years) may have a different profile in
      terms of treatment modification due to higher incidence of comorbidities and
      polypharmacy. The aim of this study was to describe the incidence of modifying or
      discontinuing first combined antiretroviral therapy regimen due to toxicity (TOX
      MOD) during the first year of treatment at the IPEC - FIOCRUZ HIV/AIDS cohort,
      Rio de Janeiro, Brazil, stratified by age. Demographic, clinical and treatment
      characteristics from antiretroviral-naive patients who first received combined
      antiretroviral therapy between Jan/1996 and Dec/2010 were collected. Incidence
      rate and confidence interval of each event were estimated using quasipoisson
      model. To estimate hazard ratio (HR) of TOX-MOD during the first year of combined
      antiretroviral therapy Cox's proportional hazards regression was applied.
      Overall, 1558 patients were included; 957 (61.4%), 420 (27.0%) and 181 (11.6%)
      were aged <40, 40-49, and >= 50 years, respectively. 239 (15.3%) events that led
      to any modifying or discontinuing within the first year of treatment were
      observed; 228 (95.4%) of these were TOX-MOD, corresponding to an incidence rate
      of 16.6/100 PY (95% CI: 14.6-18.9). The most frequent TOX-MOD during first
      combined antiretroviral therapy regimen were hematologic (59; 26.3%), central
      nervous system (47; 20.9%), rash (42; 19.1%) and gastrointestinal (GI) (38;
      16.7%). In multivariate analysis, incidence ratio of TOX-MOD during the first
      year of combined antiretroviral therapy progressively increases with age, albeit
      not reaching statistical significance. This profile was maintained after
      adjusting the model for sex, combined antiretroviral therapy regimen and year of
      combined antiretroviral therapy initiation. These results are important because
      not only patients are living longer and aging with HIV, but also new diagnoses
      are being made among the elderly. Prospective studies are needed to evaluate the
      safety profile of first line combined antiretroviral therapy on elderly
      individuals, especially in resource-limited countries, where initial regimens are
      mostly NNRTI-based.

PMID- 24029436
TI  - Epidemiology of septic arthritis of the knee at Hospital das Clinicas,
      Universidade de Sao Paulo.
AB  - BACKGROUND: Septic arthritis is an infrequent disease although very important due
      to the possibility of disastrous outcomes if treatment is not adequately
      established. Adequate information concerning the epidemiology of septic arthritis
      is still lacking due to the uncommon nature of the disease as well as the
      struggle to establish a correct case-definition. OBJECTIVE: To epidemiologically
      characterize the population seen at Hospital das Clinicas, University of Sao
      Paulo with a diagnosis of septic arthritis between 2006 and 2011. METHODS: Sixty
      one patients diagnosed with septic arthritis of the knee between 2006 and 2011
      were retrospectively evaluated. The patients' clinical and epidemiological
      characteristics, the microorganisms that caused the infection and the patients'
      treatment and evolution were analyzed. RESULTS: Septic arthritis of the knee was
      more common among men, with distribution across a variety of age ranges. Most
      diagnoses were made through positive synovial fluid cultures. The most prevalent
      clinical comorbidities were systemic arterial hypertension and diabetes mellitus,
      and the most commonly reported joint disease was osteoarthritis. Staphylococcus
      aureus was the prevailing pathogen. Fever was present in 36% of the cases. All
      patients presented elevation in inflammatory tests. Gram staining was positive in
      only 50.8% of the synovial fluid samples analyzed. Six patients presented
      complications and unfavorable evolution of their condition. CONCLUSION: S. aureus
      is still the most common pathogen in acute knee infections in our environment.
      Gram staining, absence of fever and normal leukocyte count cannot be used to rule
      out septic arthritis.

PMID- 24029427
TI  - Chromosome 2q31.1 associates with ESRD in women with type 1 diabetes.
AB  - Sex and genetic variation influence the risk of developing diabetic nephropathy
      and ESRD in patients with type 1 diabetes. We performed a genome-wide association
      study in a cohort of 3652 patients from the Finnish Diabetic Nephropathy
      (FinnDiane) Study with type 1 diabetes to determine whether sex-specific genetic
      risk factors for ESRD exist. A common variant, rs4972593 on chromosome 2q31.1,
      was associated with ESRD in women (P<5*10(-8)) but not in men (P=0.77). This
      association was replicated in the meta-analysis of three independent type 1
      diabetes cohorts (P=0.02) and remained significant for women (P<5*10(-8); odds
      ratio, 1.81 [95% confidence interval, 1.47 to 2.24]) upon combined meta-analysis
      of the discovery and replication cohorts. rs4972593 is located between the genes
      that code for the Sp3 transcription factor, which interacts directly with
      estrogen receptor alpha and regulates the expression of genes linked to
      glomerular function and the pathogenesis of nephropathy, and the CDCA7
      transcription factor, which regulates cell proliferation. Further examination
      revealed potential transcription factor-binding sites within rs4972593 and
      predicted eight estrogen-responsive elements within 5 kb of this locus. Moreover,
      we found sex-specific differences in the glomerular expression levels of SP3
      (P=0.004). Overall, these results suggest that rs4972593 is a sex-specific
      genetic variant associated with ESRD in patients with type 1 diabetes and may
      underlie the sex-specific protection against ESRD. 

PMID- 24029437
TI  - Promotion of hand hygiene strengthening initiative in a Nigerian teaching
      hospital: implication for improved patient safety in low-income health
      facilities.
AB  - BACKGROUND: Health care-associated infection remains a significant hazard for
      hospitalized patients. Hand hygiene is a fundamental action for ensuring patient
      safety. OBJECTIVE: To promote adoption of World Health Organization Hand Hygiene
      Guidelines to enhance compliance among doctors and nurses and improve patient
      safety. METHODS: The study design was a cross sectional intervention in a Federal
      Teaching Hospital South-eastern Nigeria. Interventions involved
      training/education; introduction of hand rub; and hand hygiene reminders. The
      impact of interventions and hand hygiene compliance were evaluated using World
      Health Organization direct observation technique. RESULTS: The post-intervention
      hand hygiene compliance rate was 65.3%. Hand hygiene indications showed highest
      compliance rate 'after body fluid exposure' (75.3%) and 'after touching a
      patient' (73.6%) while the least compliance rate was recorded 'before touching a
      patient' (58.0%). Hand hygiene compliance rate was significantly higher among
      nurses (72.9%) compared to doctors (59.7%) (chi(2)=23.8, p<0.05). Hand hygiene
      indication with significantly higher compliance rate was "before clean/aseptic
      procedure" (84.4%) (chi(2)=80.74, p<0.05). Out of the 815 hand hygiene practices
      recorded 550 (67.5%) were hand rub action. CONCLUSIONS: hand hygiene campaigns
      using the World Health Organization tools and methodology can be successfully
      executed in a tertiary health facility of a low-income setting with far reaching
      improvements in compliance.

PMID- 24029438
TI  - The association of HLA-DRB1 alleles and drug use with HIV infection in a Chinese
      Han Cohort.
AB  - OBJECTIVE: To investigate the relationship between the polymorphism of human
      leukocyte antigen (HLA)-DRB1 and the susceptibility and repellency of drug use
      combined with HIV infection in Chinese. METHODS: A total of 213 unrelated healthy
      people, 41 HIV-infected drug users, 24 HIV-uninfected drug users, and 64 HIV
      infected non-drug users were recruited. Their HLA-DRB1 allele frequencies were
      analyzed by PCR-SSP and allele distribution was analyzed. RESULTS: Compared with
      healthy controls, in drug users, the frequencies of HLA-DRB1 *0401-041, *1001
      were significantly higher; in HIV-infected patients, the frequencies of HLA-DRB1
      *0101-0103, *0401-0411, *1001 were significantly higher, while the frequencies of
      DRB1 *1501-1502, *1101-1105, *1301-1302, DRB4, DRB5 were significantly lower; in
      HIV-infected drug users, the frequencies of HLA-DRB1 *0101-0103, *0401-0411,
      *0801-0806, *1001, *1401/1404/1405 were significantly higher, while the
      frequencies of DRB1 *1301/1302, 1501-1502, DRB5 were significantly lower.
      CONCLUSION: There is close relationship between the polymorphism of HLA-DRB1
      alleles and drug use with HIV infection, which plays an important role in
      elucidating the pathogenesis and providing the basis for therapeutics and
      prophylaxis of patients with drug use and HIV infection.

PMID- 24029439
TI  - A simple, rapid and economic method for detecting multidrug-resistant
      tuberculosis.
AB  - OBJECTIVE: To evaluate multiplex allele specific polymerase chain reaction as a
      rapid molecular tool for detecting multidrug-resistant tuberculosis. METHODS:
      Based on drug susceptibility testing, 103 isolates were multidrug-resistant
      tuberculosis and 45 isolates were sensitive to isonicotinylhydrazine and
      rifampin. Primers were designed to target five mutations hotspots that confer
      resistance to the first-line drugs isoniazid and rifampin, and multiplex allele
      specific polymerase chain reaction was performed. Whole-genome sequencing
      confirmed drug resistance mutations identified by multiplex allele specific
      polymerase chain reaction. RESULTS: DNA sequencing revealed that 68.9% of
      multidrug-resistant strains have point mutations at codon 315 of the katG gene,
      19.8% within the mabA-inhA promoter, and 98.0% at three hotspots within rpoB.
      Multiplex allele specific polymerase chain reaction detected each of these five
      mutations, yielding 82.3% sensitivity and 100% specificity for isoniazid
      resistance, and 97.9% sensitivity and 100% specificity for rifampin resistance as
      compared to drug susceptibility testing. CONCLUSIONS: The results show that
      multiplex allele specific polymerase chain reaction is an inexpensive and
      practical method for rapid detection of multidrug-resistant tuberculosis in
      developing countries.

PMID- 24029440
TI  - Governing patient safety: lessons learned from a mixed methods evaluation of
      implementing a ward-level medication safety scorecard in two English NHS
      hospitals.
AB  - BACKGROUND: Relatively little is known about how scorecards presenting
      performance indicators influence medication safety. We evaluated the effects of
      implementing a ward-level medication safety scorecard piloted in two English NHS
      hospitals and factors influencing these. METHODS: We used a mixed methods,
      controlled before and after design. At baseline, wards were audited on medication
      safety indicators; during the 'feedback' phase scorecard results were presented
      to intervention wards on a weekly basis over 7 weeks. We interviewed 49 staff,
      including clinicians and managers, about scorecard implementation. RESULTS: At
      baseline, 18.7% of patients (total n=630) had incomplete allergy documentation;
      53.4% of patients (n=574) experienced a drug omission in the preceding 24 h;
      22.5% of omitted doses were classified as 'critical'; 22.1% of patients (n=482)
      either had ID wristbands not reflecting their allergy status or no ID wristband;
      and 45.3% of patients (n=237) had drugs that were either unlabelled or labelled
      for another patient in their drug lockers. The quantitative analysis found no
      significant improvement in intervention wards following scorecard feedback.
      Interviews suggested staff were interested in scorecard feedback and described
      process and culture changes. Factors influencing scorecard implementation
      included 'normalisation' of errors, study duration, ward leadership, capacity to
      engage and learning preferences. DISCUSSION: Presenting evidence-based
      performance indicators may potentially influence staff behaviour. Several
      practical and cultural factors may limit feedback effectiveness and should be
      considered when developing improvement interventions. Quality scorecards should
      be designed with care, attending to evidence of indicators' effectiveness and how
      indicators and overall scorecard composition fit the intended audience.

PMID- 24029441
TI  - Correlation of antibiotic prophylaxis and difficulty of extraction with
      postoperative inflammatory complications in the lower third molar surgery.
AB  - Our aim was to investigate the correlation among antibiotic prophylaxis,
      difficulty of extraction, and postoperative complications in the removal of lower
      3rd molars. A total of 1222 such extractions in 890 patients between January 2010
      and January 2012 were analysed retrospectively. The difficulty of extraction
      measured by Pederson's index, antibiotic prophylaxis with cefditoren, and
      postoperative complications were recorded. The difficulty of extraction was
      significantly associated with postoperative complications (p=0.03). There were no
      significant associations between antibiotic prophylaxis and postoperative
      complications in groups of equal difficulty ("easy" group (class I) p=1.00;
      "moderate" group (class II) p=1.00; and "difficult" group (class III) p=0.65).
      There was a small but insignificant increase in the number of dry sockets and
      infections in class III cases. In conclusion, this study provides further
      evidence that antibiotic prophylaxis for the prevention of postoperative
      inflammatory complications is unnecessary for extraction of 3rd molars.

PMID- 24029442
TI  - Toxicology screening in oral and maxillofacial trauma patients.
AB  - The role of alcohol in facial trauma is recognised but we know of no research on
      the possible contribution made by the use of illicit drugs in patients with
      facial injuries, or the interactions that may occur during anaesthesia. We aimed
      to find out whether illegal drugs were identified in the urine of patients with
      maxillofacial injuries, what substances were present, and whether patients were
      willing to disclose use of drugs at the time of injury. Over a 12-month period we
      prospectively studied consecutive patients with facial injuries who were referred
      by accident and emergency (A&E) to the department of oral and maxillofacial
      surgery (OMFS) for inpatient assessment and treatment within 24 h of injury.
      Anonymised data on patients were obtained from questionnaires that were linked to
      a urine sample provided on admission. Results were obtained using immunoassay and
      gas chromatography with mass spectrometry. A total of 105 patients with facial
      injuries were eligible and 95 (90%) provided a urine sample and completed the
      questionnaire; 2 samples were of insufficient volume and were discarded before
      analysis. Twelve patients (13%) admitted using drugs at the time of injury but 44
      (47%) samples tested positive for illegal drugs; fewer showed the presence of
      alcohol (n=37; 40%). Use of drugs, although often denied, is widespread among
      patients with facial injuries. It is important to consider the role that drugs
      have in patients who present with traumatic injuries, the interactions misused
      drugs may have with anaesthesia, and any possible benefits that targeted
      prevention strategies would have in this group.

PMID- 24029443
TI  - Reply to Dr. Papamichael et al.'s letter.

PMID- 24029444
TI  - Incidence and risk factors for medical complications and 30-day end points after
      carotid artery stenting.
AB  - With the extensive use of carotid artery stenting (CAS) surgeries, scholars are
      paying more attention to the safety and efficiency of CAS. Our study aims to
      analyze the clinical efficiency, safety, and technical feasibility of CAS surgery
      in the treatment of carotid artery stenosis. A total of 379 cases of CAS were
      collected and retrospectively analyzed. The outcomes were summarized according to
      decrease in stenosis extent, incidence of early complications after procedure, 30
      day end point events, and the follow-up data. Logistic regression was employed to
      analyze the correlations between risk factors and complications within 30 days
      and 30-day end points of stroke, myocardial infarctions (MIs), and mortality. The
      average extent of stenosis reduced from preoperative (81% +/- 17%) to
      postoperative (26% +/- 17%). In all, 53 patients had 72 medical complications,
      including 6 (1.58%) cerebral hemorrhage, 7 (1.85%) cerebral infarction, 5 (1.32%)
      transient ischemic attack (TIA), 5 (1.32%) heart failure, 10 (2.63%) symptomatic
      hypertension, 21 (5.54%) symptomatic hypotension, 10 (2.63%) symptomatic
      bradycardia, and 8 other complications; 15 patients had at least 2 complications.
      Advanced age, diabetes, and heart failure were associated with the high incidence
      of early complications (P < .05). Asymptomatic stenosis (odds ratio [OR] = 0.39,
      95% confidence interval [CI]: 0.131-1.131, P = .0426) and diabetes (OR = 3.38,
      95% CI: 1.340-8.574, P = .0099) were correlated with the incidence of 30-day end
      point events. Diabetes and symptomatic stenosis are independent risk factors for
      30-day end point events of CAS. Advanced age, hypertension, and vascular unstable
      plaque will increase the risk of postoperative complications. 

PMID- 24029445
TI  - Understanding cognitive deficits in Alzheimer's disease based on neuroimaging
      findings.
AB  - Brain amyloid can be measured using positron emission tomography (PET). There are
      mixed reports regarding whether amyloid measures are correlated with measures of
      cognition (in particular memory), depending on the cohorts and cognitive domains
      assessed. In Alzheimer's disease (AD) patients and those at heightened risk for
      AD, cognitive performance may be related to the level and extent of classical AD
      pathology (amyloid plaques and neurofibrillary angles), but it is also influenced
      by neurodegeneration, neurocognitive reserve, and vascular health. We discuss
      what recent neuroimaging research has discovered about cognitive deficits in AD
      and offer suggestions for future research. 

PMID- 24029447
TI  - Influence of weaning timing advice and associated weaning behaviours in a survey
      of black and minority ethnic groups in the UK.
AB  - OBJECTIVE: To assess understanding of the Department of Health weaning guidelines
      and weaning influences in a self-selected sample of black and minority ethnic
      (BME) parents, residing in London. DESIGN: A face-to-face, questionnaire
      facilitated survey among Black African, Black Caribbean and South Asian parents.
      SETTING: An opportunistic sample of parents was recruited from Sure Start
      centres, churches and play groups across key London boroughs. SUBJECTS: Three
      hundred and forty-nine interviews were included; 107 Black African, fifty-four
      Black Caribbean, 120 South Asian and sixty-four of Black mixed-race ethnicity.
      RESULTS: Fifty-two per cent of Black and 66 % of South Asian parents had accurate
      understanding of the guidelines. Inaccurate knowledge of the guidelines was
      associated with weaning before 17 weeks (P < 0.001); 36 % of Black Africans and
      31 % of Black Caribbeans were weaned before 4 months compared with 16 % of South
      Asians. All BME groups were most influenced by weaning information from the
      previous generations of mothers in their families, which was associated with
      earlier weaning (21.5 (SD 6.5) v. 24.1 (SD 4.2) weeks; F(2,328) = 5.79, P =
      0.003), and less so by professional infant feeding advice, which was associated
      with a later weaning age (23.7 (SD 5.1) v. 20.7 (SD 5.7) weeks; F(1,344) = 34.7,
      P < 0.001). CONCLUSIONS: Lack of awareness of the Department of Health weaning
      guidelines is common among these BME populations, whose weaning behaviour is
      strongly influenced by informal advice. Further research is necessary to
      elucidate the influences on weaning in these populations and to facilitate the
      development of infant feeding support which is salient for BME groups in the UK.

PMID- 24029448
TI  - [Irritable bowel syndrome, celiac disease and gluten].
AB  - For many years irritable bowel syndrome (IBS) and celiac disease (CD) have been
      considered 2 completely separate entities, with CD being clearly related to a
      permanent gluten intolerance and IBS having no relation with gluten ingestion.
      However IBS and CD symptoms may be indistinguishable, especially when diarrhea,
      bloating or abdominal pain predominate. In the last decade several studies have
      shown that the separation between CD and IBS is not so clear. Thus, some patients
      who have been diagnosed of IBS suffer in fact from CD. In addition, it seems that
      there is a group of patients who, without having CD, suffer gluten intolerance
      that cause them digestive symptoms similar to those of IBS. Gluten sensitivity is
      defined as the spectrum of morphological, immunological and functional
      abnormalities that respond to a gluten-free diet. This concept includes
      histological, immunological and clinical manifestations in the absence of evident
      morphological abnormalities. Therefore, it is mandatory to establish in a
      scientific way in which patients a gluten-free diet will be beneficial as well as
      when this is not justified. 

PMID- 24029449
TI  - [A 40-year-old woman with headache and diplopia].

PMID- 24029450
TI  - [Asthma: therapeutic update].

PMID- 24029451
TI  - [Lung transplantation in pulmonary fibrosis and other interstitial lung
      diseases].
AB  - BACKGROUND AND OBJECTIVE: Interstitial lung disease (ILD) is the second
      indication for lung transplantation (LT) after emphysema. The aim of this study
      is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona,
      Spain). PATIENTS AND METHODS: We retrospectively studied 150 patients, 87 (58%)
      men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One
      hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral
      lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual
      interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%)
      unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the
      functional results, complications and survival. RESULTS: The actuarial survival
      was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes
      of death included early graft dysfunction and development of chronic rejection in
      the form of bronchiolitis obliterans (BOS). The mean postoperative increase in
      forced vital capacity and forced expiratory volume in the first second (FEV1) was
      similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months.
      Sixteen percent of patients returned to work. At some point during the evolution,
      proven acute rejection was diagnosed histologically in 53 (35%) patients. The
      prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5
      years. CONCLUSIONS: LT is the best treatment option currently available for ILD,
      in which medical treatment has failed.

PMID- 24029452
TI  - [Legionellosis in children and new transmission sources].

PMID- 24029453
TI  - [Heterochromia iridis, congenital deafness and skin pigmentary abnormalities:
      Waardenburg syndrome].

PMID- 24029446
TI  - Bridging animal and human models of exercise-induced brain plasticity.
AB  - Significant progress has been made in understanding the neurobiological
      mechanisms through which exercise protects and restores the brain. In this
      feature review, we integrate animal and human research, examining physical
      activity effects across multiple levels of description (neurons up to inter
      regional pathways). We evaluate the influence of exercise on hippocampal
      structure and function, addressing common themes such as spatial memory and
      pattern separation, brain structure and plasticity, neurotrophic factors, and
      vasculature. Areas of research focused more within species, such as hippocampal
      neurogenesis in rodents, also provide crucial insight into the protective role of
      physical activity. Overall, converging evidence suggests exercise benefits brain
      function and cognition across the mammalian lifespan, which may translate into
      reduced risk for Alzheimer's disease (AD) in humans. 

PMID- 24029454
TI  - Interstitial pneumonia associated with linear immunoglobulin A/immunoglobulin G
      bullous dermatosis.
AB  - A 76-year-old man with interstitial lung disease was admitted to our institution
      after developing persistent dyspnea upon effort. He also had a relapse of bullous
      eruptions on the skin of the trunk and extremities, previously diagnosed as
      vesicular pemphigoid. Direct immunofluorescence of a skin biopsy specimen using
      fluorescence microscopy showed the linear deposition of immunglobulin A (IgA),
      IgG and C3 along the basement membrane. These findings indicated a definitive
      diagnosis of linear IgA/IgG bullous dermatosis. Chest computed tomography,
      bronchoalveolar lavage and transbronchial lung biopsy findings suggested
      nonspecific interstitial pneumonia. Direct immunofluorescence of the lung biopsy
      specimens using fluorescence microscopy also showed a deposition of IgA, IgG and
      C3 along the epithelial cell membranes and basement membranes of the bronchioles
      and alveoli. Lung disorders associated with linear IgA/IgG bullous dermatosis are
      extremely rare and, to our knowledge, this is the first report of such a case of
      interstitial pneumonia. 

PMID- 24029455
TI  - Raman spectroscopy of self-catalyzed GaAs(1-x)Sb(x) nanowires grown on silicon.
AB  - Thanks to their wide band structure tunability, GaAs(1-x)Sb(x) nanowires provide
      exciting perspectives in optoelectronic and energy harvesting applications. The
      control of composition and strain of these ternary alloys is crucial in the
      determination of their optical and electronic properties. Raman scattering
      provides information on the vibrational properties of materials, which can be
      related to the composition and strain. We present a systematic study of the
      vibrational properties of GaAs(1-x)Sb(x) nanowires for Sb contents from 0 to 44%,
      as determined by energy-dispersive x-ray analyses. We find that optical phonons
      red-shift with increasing Sb content. We explain the shift by alloying effects,
      including mass disorder, dielectric changes and ionic plasmon coupling. The
      influence of Sb on the surface optical modes is addressed. Finally, we compare
      the luminescence yield between GaAs and GaAs(1-x)Sb(x), which can be related to a
      lower surface recombination rate. This work provides a reference for the study of
      ternary alloys in the form of nanowires, and demonstrates the tunability and high
      material quality of gold-free ternary antimonide nanowires directly grown on
      silicon.

PMID- 24029456
TI  - Delays in diagnosis and treatment of breast cancer: a multinational analysis.
AB  - BACKGROUND: Reducing treatment delay improves outcomes in breast cancer. The aim
      of this study was to determine factors influencing patient- and system-related
      delays in commencing breast cancer treatment in different countries. METHODS: A
      total of 6588 female breast cancer patients from 12 countries were surveyed.
      Total delay time was determined as the sum of the patient-related delay time
      (time between onset of the first symptoms and the first medical visit) and system
      related delay time (time between the first medical visit and the start of
      therapy). RESULTS: The average patient-related delay time and total delay time
      were 4.7 (range: 3.4-6.2) weeks and 14.4 (range: 11.5-29.4) weeks, respectively.
      Longer patient-related delay times were associated with distrust and disregard,
      and shorter patient-related delay times were associated with fear of breast
      cancer, practicing self-examination, higher education level, being employed,
      having support from friends and family and living in big cities. The average
      system-related delay time was 11.1 (range: 8.3-24.7) weeks. Cancer diagnosis made
      by an oncologist versus another physician, higher education level, older age,
      family history of female cancers and having a breast lump as the first cancer
      sign were associated with shorter system-related delay times. Longer patient
      related delay times and higher levels of distrust and disregard were predictors
      of longer system-related delay times. CONCLUSIONS: The delay in diagnosis and
      treatment of breast cancer remains a serious problem. Several psychological and
      behavioural patient attributes strongly determine both patient-related delay time
      and system-related delay time, but their strength is different in particular
      countries.

PMID- 24029457
TI  - The impact of the HDI on the association of psychosocial work demands with
      sickness absence and presenteeism.
AB  - BACKGROUND: The purpose of this study was to determine whether psychosocial work
      demands have a different impact on sickness absence and presenteeism in countries
      with a high vs. countries with a low Human Development Index (HDI). METHODS: This
      article is based on an analysis of the fifth European Working Conditions Survey.
      We investigated single items as well as complex constructs and indices. Sickness
      absence and presenteeism were measured as outcome variables. Following the model
      of Karasek and Theorell, we measured the HDI at the macro level and psychosocial
      job demands at the micro level as independent variables. RESULTS: The
      multivariate multilevel analysis reveals a significant association between the
      HDI and the number of days recorded for sickness absence. In countries with a
      higher HDI, people report a lower number of days with sickness absence. Higher
      psychosocial job demands are associated with poorer health. There are significant
      cross-level interaction effects between psychosocial job demands and the HDI for
      these associations. Psychosocial job demands are stronger associated with
      sickness absence and presenteeism in high-HDI than in low-HDI countries.
      CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH: We argue that Public Health
      Actions that are connected to work characteristics need to take into
      consideration the level of HDI of the countries. In low- and high-HDI countries,
      different actions could be necessary to reach the needs of the working
      population.

PMID- 24029458
TI  - Social and immigration factors in intimate partner violence among Ecuadorians,
      Moroccans and Romanians living in Spain.
AB  - BACKGROUND: Intimate partner violence (IPV) against women occurs in all
      countries, all cultures and at every level of society; however, some populations
      may be at greater risk than others. The aim of this study was to explore IPV
      prevalence among Ecuadorian, Moroccan and Romanian immigrant women living in
      Spain and its possible association with their personal, family, social support
      and immigration status characteristics. METHODS: Cross-sectional study of 1607
      adult immigrant women residing in Barcelona, Madrid and Valencia (2011).
      Prevalence rates and adjusted odds ratios (AORs) were calculated, with current
      IPV being the outcome. Different women's personal (demographic), family, social
      support and immigration status characteristics were considered as explicative and
      control variables. All analyses were separated by women's country of origin.
      RESULTS: Current IPV prevalence was 15.57% in Ecuadorians, 10.91% in Moroccans
      and 8.58% in Romanians. Some common IPV factors were found, such as being
      separated and/or divorced. In Romanians, IPV was also associated with lack of
      social support [AOR 5.96 (1.39-25.62)] and low religious involvement [AOR 2.17
      (1.06-4.43)]. The likelihood of current IPV was lower among women without
      children or other dependents in this subgroup [AOR 0.29 (0.093-0.92)].
      CONCLUSION: The IPV prevalence rates obtained for Moroccan, Romanian and
      Ecuadorian women residing in Spain were similar. Whereas the likelihood of IPV
      appeared to be relatively evenly distributed among Moroccan and Ecuadorian women,
      it was higher among Romanian women in socially vulnerable situations related to
      family responsibilities and the lack of support networks. The importance of
      intervention in the process of separation and divorce was common to all women.

PMID- 24029459
TI  - Sonolytic degradation of butyric acid in aqueous solutions.
AB  - The sonolytic degradation of butyric acid was investigated in an ultrasonic
      reactor emitting waves at 850 kHz. The effects of the ultrasonic power, the
      initial concentration of butyric acid, and the addition of H2O2 were studied on
      the degradation of butyric acid. In the sonication of butyric acid, degradation
      degrees as high as 31.5% could be achieved at a power of 31 W, at an initial
      concentration of 2.8 mM butyric acid with the addition of 0.34 M H2O2 for a
      sonication time of 5 h. The degradation of butyric acid increased with
      irradiation time, indicating first order kinetics. 

PMID- 24029460
TI  - The removal of amoxicillin from wastewater using organobentonite.
AB  - Organobentonites used as absorbents to remove amoxicillin from wastewater have
      been investigated here because they are effective in removing organic pollutants.
      It is evident that bentonite modified with hexadecyl trimethyl ammonium (DK1) can
      effectively remove amoxicillin from aqueous solution. Batch experiments showed
      that the adsorption of amoxicillin onto DK1 fitted well to a pseudo second-order
      kinetic model with corresponding rate constants (0.0187 g/mg min at 20  degrees
      C). The Langmuir isotherm provided the highest adsorption capacity (26.18 mg/g at
      20  degrees C). Our thermodynamic study suggested that the adsorption of
      amoxicillin onto DK1 was physisorptive and endothermic in nature. Furthermore DK1
      was characterized by scanning electronic microscopy (SEM), Specific Surface Area
      (SSA), X-ray powder diffraction (XRD) and Fourier Transform Infrared (FTIR)
      spectrometer. These characterizations provided evidence of the morphological
      properties and how well the adsorption process performed. An adsorption mechanism
      including both ion-exchange and partition was proposed. Finally, DK1 was used to
      remove amoxicillin from wastewaters and the results showed 81.9% and 87.5% of
      amoxicillin was removed at 19.0 mg/L and 2.0 mg/L, respectively. 

PMID- 24029461
TI  - The effects of low impact development on urban flooding under different rainfall
      characteristics.
AB  - Low impact development (LID) is generally regarded as a more sustainable solution
      for urban stormwater management than conventional urban drainage systems.
      However, its effects on urban flooding at a scale of urban drainage systems have
      not been fully understood particularly when different rainfall characteristics
      are considered. In this paper, using an urbanizing catchment in China as a case
      study, the effects of three LID techniques (swale, permeable pavement and green
      roof) on urban flooding are analyzed and compared with the conventional drainage
      system design. A range of storm events with different rainfall amounts, durations
      and locations of peak intensity are considered for holistic assessment of the LID
      techniques. The effects are measured by the total flood volume reduction during a
      storm event compared to the conventional drainage system design. The results
      obtained indicate that all three LID scenarios are more effective in flood
      reduction during heavier and shorter storm events. Their performance, however,
      varies significantly according to the location of peak intensity. That is, swales
      perform best during a storm event with an early peak, permeable pavements perform
      best with a middle peak, and green roofs perform best with a late peak,
      respectively. The trends of flood reduction can be explained using a newly
      proposed water balance method, i.e., by comparing the effective storage depth of
      the LID designs with the accumulative rainfall amounts at the beginning and end
      of flooding in the conventional drainage system. This paper provides an insight
      into the performance of LID designs under different rainfall characteristics,
      which is essential for effective urban flood management. 

PMID- 24029462
TI  - pi and pi + sigma plasmon localization in single-walled carbon nanotube meta
      materials.
AB  - We have investigated the plasmon excitations and interband transitions in nematic
      nanotube meta-materials with different nanotube mean diameters. While the
      characteristic optical low-energy transitions give testimony to the differing
      mean diameters, the full momentum resolved pi as well as pi + sigma plasmon
      response of the meta-materials is found to be entirely invariant with the
      nanotube diameters 1 nm < d < 2 nm. We hence demonstrate that plasmons on single
      walled carbon nanotubes are fully channeled to be one dimensional in the typical
      range of nanotube diameters. The internal morphology of the meta-material offers
      a knob to uniformly tune the plasmon resonances.

PMID- 24029463
TI  - Risk prediction of subsequent early stroke in patients with transient ischemic
      attacks.
AB  - BACKGROUND: Prognostic clinical scores (ABCD2 and ABCD3-I), as well as specific
      clinical signs and symptoms (e.g. fluctuations) have been used to predict early
      stroke risk in patients admitted to hospital after transient ischemic attacks
      (TIAs). We compared the utility of these scores and signs for prognosis and
      outcome. METHODS: 235 patients with TIAs admitted to our Comprehensive Stroke
      Center entered the study. Patients were monitored over 3 days with detailed brain
      imaging [diffusion-weighted imaging (DWI) was performed either directly on
      admission or within 24 h from admission and was repeated in cases of stroke
      recurrence], vascular ultrasound imaging, repeated neurological scoring and
      continuous ECG monitoring. Duration, fluctuation of symptoms, clinical patterns
      of initial signs and/or symptoms as well as general patient characteristics and
      stroke risk factors, including atrial fibrillation (AF), were analyzed and
      recorded in our stroke databank. Fluctuation of symptoms was defined as the
      complete remitting and relapsing of TIA symptoms for >=2 times in the acute phase
      within the first 24 h. This differs from the 'dual TIA' definition of the ABCD3-I
      score, which is defined as 'an earlier TIA within 7 days of the index event'.
      ABCD2 and ABCD3-I scores were calculated and the patients were placed into three
      categories: 'low', 'moderate' and 'high' risk for every score. Risk associations
      were assessed by the chi(2) test and the phi-coefficient. RESULTS: Out of 235
      patients, 17 patients (7.2%) experienced an early stroke during hospitalization
      (mean duration 7.4 +/- 2.7 days). ABCD2 scores failed to predict early stroke (p
      = 0.544). ABCD3-I scores correlated better with early stroke recurrences (p =
      0.021). Positive DWI findings (6/17; 35.3%), presence of carotid stenosis (3/17;
      17.6%) or AF (1/17; 5.9%) alone failed to predict early stroke. Fluctuations of
      symptoms, however, showed a significant prediction for early stroke after TIA:
      13/17 (76.5%) patients (p < 0.001). The combination of symptom fluctuation and MR
      DWI-positive findings (4/17; 23.5%) also turned out to be statistically
      significant in this regard (p = 0.003), while the combination of symptom
      fluctuations with carotid stenosis >=50% did not (p = 0.151). Combining
      fluctuations with carotid stenosis and DWI-positive findings did not improve the
      result (p = 0.029). CONCLUSIONS: While the ABCD3-I score is indeed very useful,
      symptom fluctuations seem to be the best available and an easily accessible and
      applicable parameter for individual prediction of a high early stroke risk after
      TIAs.

PMID- 24029464
TI  - Anticonvulsant and sedative effects of paederosidic acid isolated from Paederia
      scandens (Lour.) Merrill. in mice and rats.
AB  - This study was designed to evaluate the anticonvulsant and sedative effects of
      paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and
      rats. In the present study, anticonvulsant activities of paederosidic acid were
      evaluated by maximal electroshock and pentylenetetrazole-induced seizures in male
      mice. Then, pentobarbital sodium-induced sleeping time and locomotor activity
      tests in mice were used to evaluate the sedative effects of paederosidic acid.
      Finally, the mechanism of paederosidic acid was explored by evaluating the
      contents of Glu and GABA in the brain, and Western blot was used to measure GAD65
      expression in the mouse brain. Paederosidic acid (5, 10, 20, and 40 mg/kg, ip)
      had significant anticonvulsant and sedative effects. Moreover, paederosidic acid
      increased brain gamma-aminobutyric acid and decreased glutamic acid in the brain,
      and it up-regulated expressions of GAD 65. In conclusion, our results suggest
      that paederosidic acid may be a promising future therapeutic agent for treatment
      of epilepsy.

PMID- 24029466
TI  - Sorting of a HaloTag protein that has only a signal peptide sequence into
      exocrine secretory granules without protein aggregation.
AB  - The mechanism involved in the sorting and accumulation of secretory cargo
      proteins, such as amylase, into secretory granules of exocrine cells remains to
      be solved. To clarify that sorting mechanism, we expressed a reporter protein
      HaloTag fused with partial sequences of salivary amylase protein in primary
      cultured parotid acinar cells. We found that a HaloTag protein fused with only
      the signal peptide sequence (Met(1)-Ala(25)) of amylase, termed SS25H,
      colocalized well with endogenous amylase, which was confirmed by
      immunofluorescence microscopy. Percoll-density gradient centrifugation of
      secretory granule fractions shows that the distributions of amylase and SS25H
      were similar. These results suggest that SS25H is transported to secretory
      granules and is not discriminated from endogenous amylase by the machinery that
      functions to remove proteins other than granule cargo from immature granules.
      Another reporter protein, DsRed2, that has the same signal peptide sequence also
      colocalized with amylase, suggesting that the sorting to secretory granules is
      not dependent on a characteristic of the HaloTag protein. Whereas Blue Native
      PAGE demonstrates that endogenous amylase forms a high-molecular-weight complex,
      SS25H does not participate in the complex and does not form self-aggregates.
      Nevertheless, SS25H was released from cells by the addition of a beta-adrenergic
      agonist, isoproterenol, which also induces amylase secretion. These results
      indicate that addition of the signal peptide sequence, which is necessary for the
      translocation in the endoplasmic reticulum, is sufficient for the transportation
      and storage of cargo proteins in secretory granules of exocrine cells.

PMID- 24029465
TI  - Reduced colonic microbial diversity is associated with colitis in NHE3-deficient
      mice.
AB  - Chronic inflammation and enteric infections are frequently associated with
      epithelial Na(+)/H(+) exchange (NHE) inhibition. Alterations in electrolyte
      transport and in mucosal pH associated with inflammation may represent a key
      mechanism leading to changes in the intestinal microbial composition. NHE3
      expression is essential for the maintenance of the epithelial barrier function.
      NHE3(-/-) mice develop spontaneous distal chronic colitis and are highly
      susceptible to dextran sulfate (DSS)-induced mucosal injury. Spontaneous colitis
      is reduced with broad-spectrum antibiotics treatment, thus highlighting the
      importance of the microbiota composition in NHE3 deficiency-mediated colitis. We
      herein characterized the colonic microbiome of wild-type (WT) and NHE3(-/-) mice
      housed in a conventional environment using 454 pyrosequencing. We demonstrated a
      significant decrease in the phylogenetic diversity of the luminal and mucosal
      microbiota of conventional NHE3(-/-) mice compared with WT. Rederivation of NHE3(
      /-) mice from conventional to a barrier facility eliminated the signs of colitis
      and decreased DSS susceptibility. Reintroduction of the conventional microflora
      into WT and NHE3(-/-) mice from the barrier facility resulted in the restoration
      of the symptoms initially described in the conventional environment.
      Interestingly, qPCR analysis of the microbiota composition in mice kept in the
      barrier facility compared with reconventionalized mice showed a significant
      reduction of Clostridia classes IV and XIVa. Therefore, the gut microbiome plays
      a prominent role in the pathogenesis of colitis in NHE3(-/-) mice, and,
      reciprocally, NHE3 also plays a critical role in shaping the gut microbiota. NHE3
      deficiency may be a critical contributor to dysbiosis observed in patients with
      inflammatory bowel disease.

PMID- 24029467
TI  - Characteristics of Vdelta1(+) and Vdelta2(+) gammadelta T cell subsets in acute
      liver allograft rejection.
AB  - BACKGROUND: To investigate the characteristics of gammadelta T cells as well as
      the Vdelta1(+) and Vdelta2(+) subsets in the peripheral blood in liver allograft
      recipients. METHODS: Sixty-three liver transplant recipients were enrolled in
      this study: 26 cases with acute allograft rejection (Gr-AR), and 37 cases with
      stable allograft liver function (Gr-SF). The frequencies of gammadelta T cells,
      the Vdelta1(+) and Vdelta2(+) subsets, and interleukin (IL)-10-producing
      Vdelta1(+) gammadelta T cells in the peripheral blood were analyzed by flow
      cytometry. The relationship between liver function parameters and the
      Vdelta1(+)/Vdelta2(+) ratio was analyzed. RESULTS: The frequency of the
      Vdelta1(+) subset and the Vdelta1(+)/Vdelta2(+) ratio in Gr-SF was significantly
      higher than that in Gr-AR; in contrast, the frequency of the Vdelta2(+) subset in
      Gr-SF was markedly lower than that in Gr-AR. In addition, there was no
      significant difference in the frequency of gammadelta T cells between the Gr-AR
      and Gr-SF groups. Moreover, there was a significant negative correlation between
      the Vdelta1(+)/Vdelta2(+) ratio with the levels of alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST) in Gr-AR. CONCLUSIONS: Vdelta1(+) gammadelta
      T cells may have a potential role in maintaining stable graft liver function, and
      Vdelta2(+) gammadelta T cells may be associated with liver allograft rejection.
      The Vdelta1(+)/Vdelta2(+) ratio could serve as a prognostic marker for acute
      rejection after liver transplantation.

PMID- 24029468
TI  - The use of pneumatic tourniquets is safe in Asians undergoing total knee
      arthroplasty without anticoagulation.
AB  - BACKGROUND: There has always been controversy surrounding the use of pneumatic
      tourniquets in total knee arthroplasty (TKA) as they have been implicated in
      venous thromboembolic events (VTE). We aimed to evaluate the incidence of
      clinically significant VTE in Asians who underwent conventional TKA under
      tourniquet throughout the duration of surgery, without post-operative chemical
      VTE prophylaxis, but using post-operative pneumatic compression devices. METHODS:
      Five hundred and thirty-one patients of a single surgeon who underwent elective
      total knee arthroplasty were retrospectively reviewed. All patients had a
      tourniquet applied to the operated limb. None of the patients received
      chemoprophylaxis against VTE. Post-operatively, only symptomatic patients were
      referred for ultrasonography. The patients were then stratified according to the
      tourniquet time: <60, 61 to 90, 91 to 120, and >120 min. The overall incidence as
      well as the incidence of venous thromboembolic events for each group was then
      calculated. RESULTS: Of the 531 patients reviewed, 3 patients suffered from deep
      venous thrombosis (DVT) while 1 patient developed a fatal pulmonary embolism
      (PE). Hence, the overall incidence of clinically significant VTE was 0.75%. The 3
      patients with DVT had tourniquet time of 61 to 90 min while the patient with PE
      had a tourniquet time of more than 120 min. CONCLUSION: With a low overall
      incidence of VTE, the use of tourniquet in Asians during conventional total knee
      arthroplasty appears safe when post-operative pneumatic compression devices are
      used instead of chemical VTE prophylaxis. However, the risk of VTE seems to
      increase with a tourniquet time of more than 60 min. LEVEL OF EVIDENCE:
      Therapeutic studies, level III.

PMID- 24029469
TI  - Open access: is the scientific quality of biomedical publications threatened?

PMID- 24029470
TI  - Effects of auto-servo ventilation on patients with sleep-disordered breathing,
      stable systolic heart failure and concomitant diastolic dysfunction: subanalysis
      of a randomized controlled trial.
AB  - BACKGROUND: Systolic heart failure (HF) is frequently accompanied by diastolic
      dysfunction and sleep-disordered breathing (SDB). OBJECTIVES: The objective of
      this subset analysis was to determine effect sizes of auto-servo ventilation (ASV
      and biphasic positive airway pressure ASV) on echocardiographic measures of
      diastolic function in patients with systolic HF and SDB. METHODS: Thirty-two
      patients with stable systolic HF, concomitant diastolic dysfunction [age 66 +/- 9
      years old, left ventricular (LV) ejection fraction: 30 +/- 7% and New York Heart
      Association class II: 72%] and SDB (apnea-hypopnea index, AHI: 48 +/- 19/h; 53%
      had predominantly obstructive sleep apnea) receiving either ASV (n = 19) or
      optimal medical treatment (control, n = 13) were analyzed in a randomized
      controlled clinical trial. Polysomnographic and echocardiographic measurements
      were obtained at baseline and after 12 weeks. RESULTS: AHI significantly improved
      in the ASV group compared to the control group (-39 +/- 18 vs. -0.2 +/- 13.2/h, p
      < 0.001). At baseline, 24 (75%) patients had impaired LV relaxation, and 8 (25%)
      had a pseudo-normalized filling pattern. At the 12-week control visit, diastolic
      function assessed by the isovolumetric relaxation time (-10.3 +/- 26.1 vs. 9.3 +/
      49.1, p = 0.48) and deceleration time (-43.9 +/- 88.8 vs. 12.4 +/- 68.8, p =
      0.40) tended to improve after ASV treatment, but did not reach statistical
      significance. Likewise, the proportion of patients whose diastolic dysfunction
      improved was nonsignificantly higher in the ASV than in the control group,
      respectively (37 vs. 15%, p = 0.25). CONCLUSIONS: ASV treatment efficiently
      abolishes SDB in patients with stable systolic HF and concomitant diastolic
      dysfunction, and was associated with a statistically nonsignificant improvement
      in measures of diastolic dysfunction. Thus, these data provide estimates of
      effect size and justify the evaluation of the effects of ASV on diastolic
      function in larger randomized controlled trials.

PMID- 24029472
TI  - [The emphasis of immune homeostasis in the treatment of the patients with
      myasthenia gravis].

PMID- 24029471
TI  - Differential immunoregulation in successful oocyte donation pregnancies compared
      with naturally conceived pregnancies.
AB  - In oocyte donation (OD) pregnancies, there is a higher level of antigenic
      dissimilarity between mother and fetus compared with naturally conceived (NC)
      pregnancies. We hypothesize that a higher degree and/or a different type of
      immunoregulation is necessary to maintain an uncomplicated OD pregnancy.
      Different immunological aspects of successful OD pregnancies (n=28) were compared
      with those of NC pregnancies (n=51), and non-donor IVF (n=20) pregnancies.
      Maternal peripheral blood mononuclear cells (mPBMCs) were characterized by flow
      cytometry; the outcome correlated with the number of mother-child HLA mismatches.
      The fetus-specific alloreactivity of mPBMCs was measured in a mixed lymphocyte
      reaction. The percentages of CD4(+)CD25(bright) and CD4(+)CD25(dim) cells were
      higher in mPBMCs of OD and IVF pregnancies compared with NC pregnancies. The
      percentage of CD4(+)CD25(dim) cells in mPBMCs of OD pregnancies correlated
      positively with the number of HLA mismatches. Functional studies showed a lower
      proliferative response to umbilical cord blood by mPBMCs in OD pregnancies. In
      conclusion, we found a higher degree of peripheral immunoregulation in OD and IVF
      pregnancies compared with NC pregnancies. A higher number of HLA mismatches in
      successful OD pregnancies leads to increased percentages of activated T cells in
      peripheral blood, but not to a higher alloreactivity to the fetus. These studies
      show that immunoregulation in OD pregnancy is different from that in NC
      pregnancies. The antigenic dissimilarity in OD pregnancies may play a role in the
      pathophysiology of preeclampsia. 

PMID- 24029473
TI  - [Fluoroquinolone associated myasthenia gravis exacerbation: clinical analysis of
      9 cases].
AB  - OBJECTIVE: To explore the characteristics of acute exacerbations of myasthenia
      gravis after fluoroquinolone exposure. METHODS: Gender, age, prior type, absolute
      score, concurrent disease, precipitated disease, use of antibiotic,
      onset/symptom/degree of exacerbation, therapeutic measures and prognosis at Month
      1 were retrospectively analyzed for 9 patients after fluoroquinolone systemic
      exposure. RESULTS: Ciprofloxacin (n = 4), levofloxacin (n = 1) and moxifloxacin
      (n = 4) exposure resulted in myasthenia gravis exacerbation. Myasthenia gravis
      exacerbations developed at 15 minutes to 4 days post-exposure. And the clinical
      scores of quantitative myasthenia gravis (QMG) increased by an average of 10. The
      main syndromes included dyspnea, diplopia, ptosis and dysphagia. All patients
      improved upon the withdrawal of fluoroquinolone in conjunctions with other
      interventions. CONCLUSION: Fluoroquinolone exposure may result in myasthenia
      gravis exacerbations in patients with underlying diseases. Healthcare
      professionals should be aware of this serious drug-disease association.

PMID- 24029474
TI  - [Changes of serum bilirubin and uric acid in patients with myasthenia gravis].
AB  - OBJECTIVE: To explore the correlations of serum total bilirubin (TBIL), direct
      bilirubin (DBIL), indirect bilirubin (IBIL) and uric acid (UA) with myasthenia
      gravis (MG). METHODS: A total of 131 MG patients were selected as MG group and
      176 healthy cases as control group. They were enrolled from the Department of
      Neurology, First Affiliated Hospital, Anhui Medical University between January
      2010 and December 2012. And the controls were recruited from a health check-up
      center. The total serum BIL and UA concentrations were measured by an enzymatic
      method. All MG patients underwent thymus computed tomography (CT) scanning.
      RESULTS: The serum levels of TBIL, IBIL and UA in patients with MG ((11.0 +/-
      0.4, 7.4 +/- 0.3, 270 +/- 70) umol/L) were significantly lower than those in
      healthy control group ((13.0 +/- 0.4, 9.6 +/- 0.3, 301 +/- 60) umol/L) (P <
      0.01). Moreover, these results were consistent when the male and female cohorts
      were investigated separately. In MG group, females had significantly lower serum
      TBIL, IBIL and UA levels ( (10.1 +/- 3.7, 6.7 +/- 2.7, 242 +/- 68) umol/L) than
      males ((12.2 +/- 5.5, 8.4 +/- 4.2, 288 +/- 73) umol/L) (P < 0.05-0.01). However,
      no difference existed when comparing different grades of MG patients according to
      the modified Osserman classification. Also no significant difference existed
      between MG patients with thymic abnormalities and those without. In comparison
      with the subjects in the reference group (total bilirubin >= 11.4 umol/L, UA >=
      279 umol/L), the odds ratio (95% CI) for MG patients in the lower tertile (total
      bilirubin < 11.4 umol/L, UA < 279 umol/L) were 1.98 (1.20-3.29) and 2.22 (1.29
      3.82) respectively after multivariable adjustment. Serum level of TBIL and UA had
      positive correlations with creatinine as indicated by Pearson correlation
      analysis (r = 0.151, P = 0.008; r = 0.301, P = 0.000). Meanwhile, serum level of
      UA had a negative correlation with high density lipoprotein-cholesterol (r = 
      0.347, P = 0.000) . CONCLUSION: Decreased serum levels of BIL and UA are closely
      correlated with MG. As a replacement therapy, administration of BIL and UA or
      theirs precursors may offer benefits to the MG patients.

PMID- 24029475
TI  - [Experimental autoimmune model of muscle-specific kinase specific myasthenia
      gravis in rats].
AB  - OBJECTIVE: To establish the experimental autoimmune Lewis rat model of myasthenia
      gravis (EAMG) specific for muscle-specific kinase (MuSK). METHODS: Lewis rats
      were immunized subcutaneously with a single injection of 200 ul of MuSK (50/100
      ug) emulsified in complete Freund's adjuvant (CFA). And MuSK was expressed
      according to the murine gene of MuSK (AY360453). Control rats were immunized with
      CFA alone. All rats were observed every other day in a blinded fashion for
      fatigue characteristics. The clinical symptoms were graded between 0 and 3. And
      the clinical scores were recorded. The serum levels of anti-MuSK IgG at Days 7
      and 57 were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: The
      clinical symptoms of myasthenia gravis (MG) appeared at Day 16 and peaked at Days
      18-22. The serum levels of anti-MuSK IgG were markedly elevated in the
      experimental groups compared with the control group. CONCLUSION: EAMG induced by
      MuSK is successfully established in rats. And this animal model may help us
      elucidate the pathogenesis of anti-MuSK myasthenia (AMM) and discover new drug
      therapy in the future.

PMID- 24029476
TI  - [Anesthetic management for pediatric congenital laryngomalacia].
AB  - OBJECTIVE: To explore our experience of anesthetic management for pediatric
      congenital laryngomalacia operation. METHODS: A total of 27 pediatric patients
      with congenital laryngomalacia were treated at our hospital between December 2010
      and November 2012. All patients were anesthetized by intravenous anesthesia of
      propofol-remifentanil and spontaneous breathing. Oxygen was insufflated at a rate
      of 4 L/min through an endotracheal tube near glottis. Propofol was set at a
      constant rate of 100 ug . kg(-1) . min(-1). The initial dose of remifentanil at
      0.05 ug.kg(-1).min(-1) was adjusted in 0.05 ug.kg(-1).min(-1) increments to
      titrate a 50% reduction in baseline respiratory rate. Heart rate (HR), mean
      arterial pressure, pulse oxygen saturation (SpO2), respiratory rate (RR),
      operation time, anesthesia time and remifentanil rate were recorded. Adverse
      events and interventions were also examined. RESULTS: Comparison with induction
      of anesthesia, HR and RR changed significantly intraoperatively (P < 0.05). MAP,
      SpO2 were no significantly change during operation (P > 0.05). The induction time
      was 9-12 min and the highest remifentanil rate stood at (0.18 +/- 0.03) ug.kg(
      1).min(-1). Body movements occurred in 3 (11%) patients and a bolus of propofol
      was administered. Desaturation below 95% occurred in 2 (7%) patients in which
      interventions were offered by decreasing the remifentanil infusion rate. No
      complications such as cough, hypoxemia, laryngospasm or bronchospasm, nausea or
      vomiting, arrhythmia were observed. CONCLUSION: Key points of anesthetic
      management for pediatric congenital laryngomalacia include sufficient
      preoperative evaluation, spontaneous respiration anesthesia technique with total
      intravenous anesthesia, suitable anesthesia depth and intensive intraoperative
      monitoring.

PMID- 24029477
TI  - [Value of dynamic arterial elastance in the predication of arterial pressure
      response to volume loading in shock patients].
AB  - OBJECTIVE: To explore the value of dynamic arterial elastance (Eadyn) in the
      predication of arterial pressure response to volume loading in shock patients.
      METHODS: A total of 32 patients with pulse indicator continuous cardiac output
      (PICCO) monitoring at our intensive care unit from January 2011 to December 2012
      were retrospectively studied. The decision of fluid replacement was based upon
      the presence of shock (mean arterial pressure (MAP) <= 65 mm Hg, systolic
      arterial pressure <90 mm Hg or a decrease of 40 mm Hg from baseline) and
      preserved volume responsiveness condition with a stroke volume variation (SVV)
      value >= 10%. According to the MAP increase after volume loading, they were
      classified into MAP responders (>= 15%) and MAP nonresponders (<15%)
      respectively. The goal was to investigate the influencing factors of the changes
      of MAP after volume loading and predict the arterial pressure response to volume
      loading. RESULTS: Significantly different between MAP responders and MAP
      nonresponders, baseline Eadyn was an effective predictor of MAP increase after
      volume loading. The area under the ROC curve was 0.95 for the prediction of
      volume loading on MAP for Eadyn at baseline (P < 0.01). A baseline Eadyn value
      >0.85 predicted a MAP increase after volume administration with a sensitivity of
      89.5% and a specificity of 92.3%. CONCLUSION: Baseline Eadyn may predict
      accurately arterial pressure response in MAP to volume loading in shock patients.

PMID- 24029478
TI  - [Effects of posterior tibial slope on non-contact anterior cruciate ligament
      rupture and stability of anterior cruciate ligament rupture knee].
AB  - OBJECTIVE: To retrospectively explore the correlation between anterior cruciate
      ligament (ACL)-ruptured knees, stability of ACL-rupture knee and posterior tibial
      slope (PTS). METHODS: From January 2008 to October 2012, 150 knees with ACL
      rupture underwent arthroscopic surgery for ACL reconstruction. A control group
      was established for subjects undergoing arthroscopic surgery without ACL rupture
      during the same period. PTS was measured on a digitalized lateral radiograph.
      Lachman and mechanized pivot shift tests were performed for assessing the
      stability of knee. RESULTS: There was significant difference (P = 0.007) in PTS
      angle between the patients with ACL rupture (9.5 +/- 2.2 degrees) and the control
      group (6.6 +/- 1.8 degrees). Only among females, increased slope of tibial
      plateau had effect on the Lachman test. There was a higher positive rate of pivot
      shift test in patients of increased posterior slope in the ACL rupture group.
      CONCLUSION: Increased posterior tibial slope (>6.6) appears to contribute to non
      contact ACL injuries in females. And the changes of tibial slope have no effect
      upon the Lachman test. However, large changes in tibial slope affect pivot shift.

PMID- 24029479
TI  - [Study of cortical thinning in the patients with type 2 diabetes mellitus and the
      recovering effect of the insulin therapy].
AB  - OBJECTIVE: To explore the cortical thickness changes in the patients with type 2
      diabetes mellitus and the effects of the insulin therapy on the brain using whole
      brain cortical thickness mapping. METHODS: High resolution three-dimensional T1
      weighted fast spoiled gradient recalled echo MRI images were obtained from 11
      normal controls and 11 patients with type II diabetes at baseline level (before
      insulin therapy) and follow-up level (after insulin therapy for 1 year). The
      whole brain cortical thickness map was calculated by the closest point
      methods.The cortical thickness of each brain region was calculated using the
      automatic region of interest. The paired t test was performed for the mean
      cortical thickness. RESULTS: The mean cortical thickness of bilateral hemisphere
      and whole brain was decreased in the patients with type 2 diabetes mellitus
      compared with normal controls (P < 0.05).After insulin therapy 1 year, the mean
      cortical thickness of right hemisphere and whole brain at follow-up was
      significantly increased compared with that at baseline (P < 0.05), and the mean
      cortical thickness of left hemisphere showed no significant difference between
      baseline and follow-up (P > 0.05). Mean cortical thickness over each brain region
      demonstrated that increased cortical thickness were mainly located in the left
      medial orbitofrontal gyrus, bilateral pars opercularis, right supramarginal
      gyrus, right lateral occipital gyrus, left calcarine gyrus, right fusiform gyrus,
      bilateral inferior temporal gyri, middle temporal gyri, left caudal anterior
      cingulate, bilateral entorhinal cortex, left parahippocampal cortex, right
      insular lobe and right rostral anterior cingulate. CONCLUSION: Cortical thinning
      was investigated in the patients with type 2 diabetes mellitus compared with
      normal controls, and wide cortical thickening was demonstrated after insulin
      therapy for 1 years.The precise mechanism should be further explored.

PMID- 24029480
TI  - [Application value of multiple phase subtraction imaging of dynamic contrast
      enhanced magnetic resonance imaging in common breast tumor].
AB  - OBJECTIVE: To evaluate the application value of multiple phase subtraction
      imaging of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in
      common breast tumor. METHODS: All radiographic and MRI data of 72 patients with
      histological proved common breast tumor were analyzed retrospectively. Prior to
      an injection of gadolinium-diethylenetriaminepentaacetate (GD-DTPA), 3D mask
      scans were performed. Then 9 consecutive phases of imaging were acquired. After
      the drawing of time-signal intensity curve, he first and second phases were
      selected to perform subtraction with the mask, rebuild 3D maximum intensity
      projection and analyze the application value of subtracted and 3D maximum
      intensity projection (MIP) reformation images. Chi-square test was used for the
      analyses of benign and malignant breast tumors. RESULTS: There were 83 lesions in
      72 patients. Among 18 cases of fibro adenoma, 23 lesions had no tumor vessel. For
      the detecting ratio of lesions, the first and second phase subtraction imaging
      had no statistics difference. Only one intraductal papilloma with ductal
      carcinoma in situ (DCIS) had tumor vessel in 4 intraductal papilloma patients.
      Among 5 DCIS cases, one of them had small curved tumor vessel. And 51 lesions
      were found in 45 infiltrating ductal carcinoma (IDC) cases. Tumor vessels could
      be seen in all IDC cases. And 37 cases had multiple tumor vessels while 8 cases
      had single tumor vessel. When the first phase was used for subtraction, 36
      lesions were found. On the other hand, 51 lesions were found in the second phase
      subtraction. There were significant differences between them. CONCLUSION: No
      significant differences exist in benign breast tumor on differential phase
      subtraction images of DCE-MRI, but there are significant differences in malignant
      breast tumor. It is very important to detect the lesions and show the tumor
      vessels by rebuilding multiple phase subtraction.

PMID- 24029481
TI  - [Surgical treatment and prognostic analyses of bronchopulmonary carcinoid
      tumors].
AB  - OBJECTIVE: To explore the surgical treatment and prognostic factors of
      bronchopulmonary carcinoid tumors (BPC). METHODS: The clinical data of 65
      patients undergoing surgery for BPC from May 1999 to December 2007 were reviewed
      retrospectively. The predictors of univariate and multivariate analyses included
      gender, age, smoking history, pathological type and tumor stage. RESULTS: The
      procedures included segmentectomy (n = 1), lobectomy (n = 36), bilobectomy (n =
      6), sleeve resection (n = 4), pneumonectomy (n = 11), carinal resection (n = 2),
      bronchoplastic resection (n = 4) and exploratory thoracotomy (n = 1). The 1- , 3-
      and 5-year overall survival rates were 86.2%, 73.8% and 64.6% respectively.
      Univariate analysis showed that gender (P = 0.029), age (P = 0.003), smoking
      history (P = 0.039), pathological type (P < 0.01), tumor stage (P < 0.01),
      postoperative radiochemotherapy (P < 0.01), lymph node metastasis (P < 0.01) and
      surgical type (P = 0.042) were prognostic factors. And multivariate analysis
      revealed that pathological type (P = 0.019) and lymph node metastasis (P < 0.01)
      were independent prognostic factors. CONCLUSION: Surgery remains a first-choice
      for BPC. The major resection procedure is anatomical lobectomy or pneumonectomy.
      Both pathological type and lymph node metastasis are independent prognostic
      factors.

PMID- 24029482
TI  - [Analysis of cardiopulmonary bypass diluted autologous blood transfusion: a
      report of 5000 cases].
AB  - OBJECTIVE: To explore the clinical application and experience of cardiopulmonary
      bypass (CPB) diluted autologous transfusion so as to provide clinical rationales
      for blood conservation. METHODS: At Department of Cardiothoracic Surgery, First
      Affiliated Hospital, Zhengzhou University, the clinical data were reviewed for
      5000 CPB surgical patients without banked blood from September 1996 to March 2012
      to analyze the clinical application of autologous blood transfusion and summarize
      the experience of depth hemodilution. No significant changes occurred in blood
      pressure, central venous pressure or heart rate after blood collection. The
      values of blood gases stayed within the normal perioperative range. The collected
      blood and all the remaining blood in CPB machine were reinfused to bring the
      postoperative level of Hb to over 90 g/L. Only 129 cases on a second thoracotomy
      for hemostasis required banked blood transfusion because of hemogloblin (Hb)
      under 70 g/L. RESULTS: Hb, hematocrit (Hct), pH, base excess (BE), lactate (Lac),
      cerebral oxygen saturation (rSO2) and arterial oxygen saturation (SaO2) indicated
      a statistically significant during CPB compared with pre-anesthetic (P < 0.05).
      The remaining indicators stayed within the normal perioperative range except for
      Hb and Hct. There were 146 cases of deaths. And the causes were postoperative low
      cardiac output (n = 34), cerebrovascular accident (n = 48), malignant arrhythmias
      (n = 28) and lung infection and multiple organ dysfunction (n = 36). The case
      fatality rate was merely 2.92%. All survivors recovered well and no heart, brain,
      kidney or other complications occurred. CONCLUSION: Hct 15%-19% depth of
      hemodilution with proper cooling and anesthetic management during cardiopulmonary
      bypass is both safe and feasible. And neutralization heparinemia in stored blood
      before CPB by protamine is one of the effective methods of blood conservation.

PMID- 24029483
TI  - [Pelvic retroperitoneal tumors: clinical analysis of 16 cases].
AB  - OBJECTIVE: To explore the diagnostic rationales for pelvic retroperitoneal tumors
      and summarize their therapeutic regimens. METHODS: A total of 16 retroperitoneal
      tumor patients were recruited. And their general information, previous medical
      history, physical examinations, auxiliary tests, surgical findings and
      postoperative pathological results were analyzed. RESULTS: Two cases were
      diagnosed through preoperative magnetic resonance imaging (MRI) while others
      found intraoperatively. Complete tumor resection was performed in all except for
      one case. Postoperative pathological examinations revealed 10 benign cases. And
      there was one case of pelvic endometriosis (mild cytologic atypia). Five cases
      were malignant. The operation duration was 1.45-8.5 hours and peri-operative
      bleeding volume 50-5000 ml. Among them, 12 patients had heavy adhesion in pelvic
      cavity, 7 cases underwent operations collaboratively with related departments
      because of surgical difficulties and vascular injury and bladder rupture occurred
      in 1 case. During the follow-ups, one case was lost, two patients died from
      disease recurrence and another one had a postoperative relapse at Month 4. The
      other 12 cases recovered well and had no recurrence. CONCLUSION: Surgery remains
      a key for retroperitoneal tumors. With a low diagnostic rate, they are often
      found surprisingly intraoperatively. Because of surgical difficulties and
      frequent complications, multi-departmental collaboration is necessary.
      Preoperative correct diagnosis and adequate preoperative preparation are
      essential. And MRI is an effective auxiliary examination.

PMID- 24029484
TI  - [Effects of tempol on white matter lesions and cognitive impairment in a rat
      model of chronic cerebral hypoperfusion].
AB  - OBJECTIVE: To assess the neuroprotective effect of Tempol, an antioxidant acting
      as a superoxide dismutase mimic, on white matter lesions and cognitive impairment
      in rats with chronic cerebral hypoperfusion. METHODS: Chronic cerebral ischemia
      was induced by permanent occlusion of bilateral common carotid arteries (2-VO) in
      male Wistar rats. The animals were divided into sham operation, saline-treated,
      Tempol (8 mg/kg) and Tempol (30 mg/kg) groups (n = 15 each). Performance of
      Morris water maze task and Western blot for myelin basic protein (MBP), amyloid
      precursor protein (APP) and 4-hydroxy-2-nonenal (HNE) modified proteins were
      analyzed at 6 weeks post-hypoperfusion. RESULTS: Tempol reduced the escape
      latency of Morris water maze post-hypoperfusion in comparison with the saline
      treated rats (P < 0.05). The mean relative optical density of MBP in the white
      matter was significantly higher in Tempol (8 mg/kg) group (0.82 +/- 0.17) and
      Tempol (30 mg/kg) group (0.91 +/- 0.15) than saline-treated group (0.44 +/- 0.13,
      all P < 0.01). The mean relative optical density of APP in white matter was
      significantly lower in Tempol (8 mg/kg) group (0.55 +/- 0.13) and Tempol (30
      mg/kg) group (0.46 +/- 0.15) than saline-treated group (0.96 +/- 0.19, all P <
      0.01). The mean relative optical density of HNE-modified protein in white matter
      was significantly lower in Tempol (8 mg/kg) group (0.20 +/- 0.035) and Tempol (30
      mg/kg) group (0.18 +/- 0.031) than saline-treated group (0.29 +/- 0.039, all P <
      0.01). CONCLUSION: Tempol ameliorates cognitive impairment by preventing white
      matter lesions induced by chronic cerebral hypoperfusion in rats. And it may
      protect white matter lesions in hypoperfused rats through reducing the formation
      of lipid peroxidation.

PMID- 24029485
TI  - [Experimental study of repairing femoral bone defects with nHA/RHLC/PLA scaffold
      composite with endothelial cells and osteoblasts in canines].
AB  - OBJECTIVE: To explore whether a tissue-engineered construct composed of
      autogenous endothelial cells, osteoblasts and a new bioresorbable nano
      hydroxyapatite/recombinant human-like collagen/polylactic acid (nHA/RHLC/PLA)
      would enhance bone regeneration and repair femoral head defects in canine models.
      METHODS: The bone marrow stem cells (BMSCs) were isolated from bone marrow of
      canine ilium and cultured in Dulbecco's modified eagle medium:nutrient mixture F
      12 culture media for 1 week and the second-generation BMSCs were further induced
      by osteogenic medium (1*10(-8) mol/L dexamethasone, 10 mmol/L B-sodium
      glycerophosphate and 50 ug/ml vitamin C) and by endothelial cell grow medium
      (vascular endothelial growth factor and basic fibroblast growth factor) for 14
      days in vitro. Thus BMSCs were induced into ECs and OBs. After the second
      passage, cells were digested and collected.And cell density was adjusted to
      1.0*10(6)/ml.The cells and nHA/RHLC/PLA scaffold were co-cultured for 2-4 hours
      then nHA/RHLC/PLA scaffold composites prepared. Cavity defects of 8 mm in
      diameter and 10 mm in height were made in femoral heads.The nHA/RHLC/PLA scaffold
      composited with ECs and osteoblasts (OBs) (group A) and composited with OBs
      (group B) were inserted into different defects while cell-free nHA/RHLC/PLA
      scaffold served as controls (group C). New bone formation and defect repair were
      evaluated at 3 and 6 months by radiographic examination, histology and bone
      histomorphometry. RESULTS: New bone formation was evident as early as 3 months in
      groups A, B and C.At 6 months, abundant bone tissue within defects was observed
      in group A. The control animals with cell-free scaffold showed less bone
      formation at both timepoints.The scaffold of nHA/RHLC/PLA was degraded and
      absorbed gradually with the formation of new bone tissues.Histology and bone
      histomorphometry further revealed significantly increased trabecular bones in
      group A compared with groups B and C at 6 months postimplantation (P < 0.01).
      CONCLUSION: More abundant new bone tissue may be found in the bone defect areas
      implanted with osteoblast-endotheliocyte composite than osteoblasts composite and
      scaffold materials only.ECs and osteoblasts derived from BMSC are ideal seed
      cells for repairing femoral head defects.

PMID- 24029486
TI  - [Inhibition of GRP78 expression reverses cisplatin resistance in human ovarian
      cancer].
AB  - OBJECTIVE: To explore the effects of GRP78 suppression on the sensitivity to
      cisplatin and elucidate the role and mechanism of GRP78 in ovarian cancer
      cisplatin resistance. METHODS: The GRP78 siRNA expression plasmid was constructed
      to suppress GRP78 expression. Cell viability was detected by methyl thiazolyl
      tetrazolium (MTT) assay. Endoplasmic reticulum stress-related apoptosis related
      protein expressions were detected by reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blot. And cell apoptosis was detected by flow
      cytometry. RESULTS: The expressions of GRP78, CHOP and cleaved-caspase 4 were
      induced significantly by cisplatin (6 mg/L) in SKOV3 cells. And the expression of
      GRP78 was induced significantly by cisplatin in SKOV3/DDP cells. But the
      expressions of CHOP and cleaved-caspase 4 showed no significant difference.
      Inhibition of GRP78 expression and cisplatin combined treatment significantly
      increased the expressions of cleaved-caspase 4 and cleaved-caspase 3 in SKOV3/DDP
      cells. Inhibition of GRP78 expression reduced the cisplatin-induced up
      regulations of p-Akt and p-mTOR and induced XBP1 mRNA shear expression and CHOP
      mRNA expression. CONCLUSION: Inhibition of GRP78 expression reverses cisplatin
      resistance in SKOV3/DDP cells. The mechanism may be through the activity of
      Akt/mTOR signaling pathway, CHOP expression levels and caspase activity.

PMID- 24029487
TI  - [Modulation of RhoA/Rho kinase on migration, invasion and proliferation of
      fibroblast like synoviocytes from patients with rheumatoid arthritis].
AB  - OBJECTIVE: To evaluate the modulation of RhoA/Rho kinase (ROCK), a small Rho
      GTPase, on migration, invasion and proliferation of fibroblast like synoviocytes
      (FLS) from rheumatoid arthritis (RA) patients. METHODS: RA FLS were collected
      from active RA patients. And 10% fetal bovine serum (FBS) and interleukin-1beta
      (IL-1beta) were used as stimuli in migration and proliferation experiments
      respectively. RhoA activity was measured by pull down assay while ROCK activity
      by Western blot. FLS migration and invasion in vitro were measured by the
      Transwell chamber method. And thiazolyl blue tetrazolium bromide (MTT) test was
      used to detect cell proliferation. RESULTS: There were increased activities of
      RhoA and ROCK in ex vivo FLS from RA versus OA patients and healthy control. The
      migrated cell number of FBS-induced, C3-treated and Y27632-treated groups was 85
      +/- 14, 51 +/- 15 and 42 +/- 11 respectively. The Matrigel invading cell number
      of 3 groups was 64 +/- 13, 39 +/- 12 and 26 +/- 9 respectively. Statistical
      differences existed in cell number between FBS-induced, C3-treated or Y27632
      treated group (P < 0.05) in above migration and invasion experiments. Inhibition
      of RhoA and ROCK activity also suppressed the cytoskeletal reorganization and
      proliferation of RA FLS. CONCLUSION: Increased RhoA/ROCK activity may contribute
      to abnormal migration, invasion and proliferation of RA FLS. Thus inhibition of
      ROCK activity may be a new therapeutic target for RA.

PMID- 24029488
TI  - Encapsulation of simvastatin in PLGA microspheres loaded into hydrogel loaded BCP
      porous spongy scaffold as a controlled drug delivery system for bone tissue
      regeneration.
AB  - The main objective of this study was to fabricate a controlled drug delivery
      which is simultaneously effective for bone regeneration. We have encapsulated
      simvastatin, which enhances osteoblastic activity, in the poly (lactic-co
      glycolic acid) microspheres. Loading of these microspheres inside the spongy
      scaffold of biphasic calcium phosphate with the help of Gelatin (Gel) hydrogel
      controls the delivery of the drug, and ensures a more favorable drug release
      profile. As a result, some significant benefits have been achieved, such as
      higher mechanical strength, excellent biocompatibility in in vitro experiments.
      For determining the characteristics of the composite scaffold, several analysis,
      such as scanning electron microscope, EDX, X-ray diffraction, FT-IR, and porosity
      were carried out. The in vitro drug release profile clearly indicates that
      simvastatin release from the microsphere was more controlled and prolonged after
      loading in the scaffold. Biocompatibility was certainly higher for the final
      composite scaffold compared to drug unloaded scaffold, as assessed through MTT
      assay and Confocal imaging with MC3T3-E1 pre-osteoblast cells. Cell attachment
      and proliferation were certainly higher in the presence of drug loaded
      microspheres. Bone remodeling gene and protein expression were observed by real
      time polymerase chain reaction and Western blot respectively. Simvastatin loaded
      scaffold exhibited the best results in every determination which was carried out.

PMID- 24029489
TI  - Drug-eluting cements for hard tissue repair: a comparative study using vancomycin
      and RNPA1000 to inhibit growth of Staphylococcus aureus.
AB  - Bone cement used in orthopaedic applications can become colonized with bacterial
      biofilms, resulting in severe medical complications. Consequently, bone cements
      are often loaded with antibiotics in an effort to prevent bacterial colonization.
      However, current formulations may not release antibiotics into the environment at
      sufficient and sustained concentrations required to impede bacterial growth or
      may be incompatible with antibiotics that are effective against the colonizing
      organism. Thus, new cement formulation options are needed. This report describes
      the performance of a novel SiO2-TiO2-ZnO-CaO-SrO-based glass polyalkenoate cement
      as a carrier of antimicrobials active against Staphylococcus aureus, the
      predominant cause of orthopaedic biofilm-associated infections. The antibiotic
      vancomycin and a novel Staphylococcus aureus RnpA inhibitor under pre-clinical
      development, RNPA1000, were included in these studies. Rheological testing
      characterized the workability of the glass polyalkenoate cement over a range of
      powder-to-liquid ratios and polyacrylic acid concentrations and revealed that the
      most suitable powder-to-liquid ratio was 2/1.25 with 40 wt% polyacrylic acid.
      Loading glass polyalkenoate cement with either 20-30% RNPA1000 or vancomycin
      prevented bacterial growth. However, longer incubations allowed for
      Staphylococcus aureus colonies to form near the vancomycin-infused cement,
      indicating that vancomycin may not be suitable for long-term biofilm inhibition
      in comparison to RNPA1000. Scanning electron microscopy and energy-dispersive X
      ray analyses confirmed successful incorporation RNPA1000 into the cement matrix
      and were indicative of its slow release. These studies establish a drug-eluting
      formulation of glass polyalkenoate cement with great potential in orthopaedic
      implants that incorporates known antibiotics as well as RNPA1000 to prevent
      growth of the dangerous pathogen Staphylococcus aureus.

PMID- 24029490
TI  - Novel avian-origin influenza A (H7N9) virus attaches to epithelium in both upper
      and lower respiratory tract of humans.
AB  - Influenza A viruses from animal reservoirs have the capacity to adapt to humans
      and cause influenza pandemics. The occurrence of an influenza pandemic requires
      efficient virus transmission among humans, which is associated with virus
      attachment to the upper respiratory tract. Pandemic severity depends on virus
      ability to cause pneumonia, which is associated with virus attachment to the
      lower respiratory tract. Recently, a novel avian-origin H7N9 influenza A virus
      with unknown pandemic potential emerged in humans. We determined the pattern of
      attachment of two genetically engineered viruses containing the hemagglutinin of
      either influenza virus A/Shanghai/1/13 or A/Anhui/1/13 to formalin-fixed human
      respiratory tract tissues using histochemical analysis. Our results show that the
      emerging H7N9 virus attached moderately or abundantly to both upper and lower
      respiratory tract, a pattern not seen before for avian influenza A viruses. With
      the caveat that virus attachment is only the first step in the virus replication
      cycle, these results suggest that the emerging H7N9 virus has the potential both
      to transmit efficiently among humans and to cause severe pneumonia. 

PMID- 24029492
TI  - Fractionation in normal tissues: the (alpha/beta)eff concept can account for dose
      heterogeneity and volume effects.
AB  - The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely
      used in external-beam radiotherapy to derive a new tumour dose prescription such
      that there is normal-tissue (NT) iso-effect when changing the fraction size
      and/or number. However, as conventionally applied, the WIF is invalid unless the
      normal-tissue response is solely determined by the tumour dose. We propose a
      generalized WIF (gWIF) which retains the tumour prescription dose, but replaces
      the intrinsic fractionation sensitivity measure (alpha/beta) by a new concept,
      the normal-tissue effective fractionation sensitivity, [Formula: see text], which
      takes into account both the dose heterogeneity in, and the volume effect of, the
      late-responding normal-tissue in question. Closed-form analytical expressions for
      [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i)
      uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter
      n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose
      distributions and arbitrary n, a numerical solution for [Formula: see text]
      exhibits a weak dependence on the number of fractions. As n is increased,
      [Formula: see text] increases from its intrinsic value at n = 0 (100% serial
      normal-tissue) to values close to or even exceeding the tumour (alpha/beta) at n
      = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text]
      corresponding to the most conformal dose distributions. Applications of this new
      concept to inverse planning and to highly conformal modalities are discussed, as
      is the effect of possible deviations from LQ behaviour at large fraction sizes. 

PMID- 24029491
TI  - Establishing polar identity in gram-negative rods.
AB  - In rod shaped bacteria, numerous cellular components are targeted to the cell
      poles, and such localization is often important for optimal function. In
      particular, recognition of poles is often linked to division site selection,
      chromosome segregation, chemotactic signaling, and motility. Recent advances in
      understanding polarity include identification of a Vibrio cholerae protein that
      mediates polar localization of a chromosome origin and chemotaxis clusters, as
      well as a downstream protein that contributes solely to localization of
      chemotaxis proteins. In Caulobacter crescentus, the molecular mechanisms by which
      polar determinants and effectors are localized, and the key roles for nucleotide
      dependent switches, have been defined. Finally, roles for, and interactions
      between, factors that mediate environmentally determined polarity in Myxococcus
      xanthus have recently been characterized. 

PMID- 24029493
TI  - Long QT interval in a patient after out-of-hospital cardiac arrest with
      hypocalcaemia, undergoing therapeutic hypothermia.
AB  - A 53-year-old woman was hospitalized after out-of-hospital cardiac arrest due to
      ventricular fibrillation. Initial electrocardioagram showed sinus rhythm of 117
      beats per minute, 452 ms QTc interval, ST-segment depression up to 1 mm in V(2)
      V(6), and ST-elevation in lead aVR. Patient was treated with primary coronary
      angioplasty and therapeutic hypothermia, during which QTc interval prolonged up
      to 616 ms and Osborn wave was seen in lead V(4), along with elevation of ST
      segment in I, II, III, aVF, V(5) and V(6); negative T waves in I, II, aVL, aVF,
      and V(2)-V(6). Laboratory test results showed hypocalcaemia. After rewarming and
      ion correction QT abnormalities resolved.

PMID- 24029494
TI  - The characteristics and prognostic predictors of unplanned hospital admission
      within 72 hours after ED discharge.
AB  - OBJECTIVES: The aims of this study were (1) to identify the characteristics of
      patients who return to the emergency department (ED) within 72 hours and are
      admitted to the hospital and (2) to identify the characteristics and predictors
      of in-hospital mortality subgroup. METHODS: This study was conducted in a
      tertiary teaching hospital to identify characteristics of adult nontraumatic
      revisit-admission patients from January 1 to December 31, 2011. Demographic data,
      cause of revisit, and the underlying diseases as well as the in-hospital
      complications were reviewed. RESULTS: Of the 72188 ED discharged patients, 690
      revisit-admission patients were enrolled. The top 3 disease classifications were
      infection (38.7%), neurology (11.3%), and gastroenterology (11.2%). The etiology
      of the revisit included recurrent symptoms (72%), disease complications (15.8%),
      and inadequate diagnosis (12.1%). A total of 150 patients (21.7%) had
      complications, including receiving operation (17.2%), intensive care unit
      admission (4.2%), and cardiovascular conditions (2.5%). Forty-nine patients
      (7.1%) died during hospitalization owing to sepsis (57.1%), malignancy (34.7%),
      cardiogenic diseases (4.1%), and cerebrovascular conditions (4.1%). The
      nonsurvival group was older (64.1 +/- 15.3 vs 55.7 +/- 17.8; P < .001), had more
      patients with a diagnosis of moderate to severe liver disease (18.4% vs 4.8%; P <
      .001), malignancy (69.3% vs 20.1%; P < .001), and metastatic solid tumor (38.8%
      vs 6.2%; P < .001). CONCLUSIONS: Age and diagnosis with malignancy, metastatic
      tumors, or moderate-to-severe liver disease were predictors of in-hospital
      mortality among 72-hour revisit-admission patients.

PMID- 24029495
TI  - Clinical practice guidelines for the treatment of invasive Aspergillus infections
      in adults in the Middle East region: Expert panel recommendations.
AB  - The incidence of invasive Aspergillus infections in the Middle East continues to
      rise with the increase in the number of immunocompromised patients, and carries
      significant morbidity and mortality. A panel of experts analysed the evidence
      from the most recent international guidelines and relevant published literature
      to reach consensus and develop clear clinical practice guidelines to aid
      diagnosis and treatment of invasive Aspergillus infections in the Middle East.
      Disease-specific recommendations were provided for the management of invasive
      aspergillosis. The expert panel acknowledged that these guidelines should be
      followed as closely as possible but used alongside clinical judgement.

PMID- 24029496
TI  - [Management of chronic refractory neuropathic pain using posterior cord
      stimulation in a patient with congenital spondyloptosis].

PMID- 24029497
TI  - Cantharidin-mediated ultrastructural and biochemical changes in mitochondria lead
      to apoptosis and necrosis in murine Dalton's lymphoma.
AB  - Cantharidin, a type of terpenoid, is the blistering agent of blister beetles
      frequently used in traditional medicine. The isolation and anticancer activity of
      cantharidin from blister beetles, Mylabris cichorii has been recently reported by
      us. This study deals with changes in mitochondrial structure and function and
      understanding their significance in the underlying mechanism(s) in cantharidin
      mediated antitumor effects in Dalton's lymphoma (DL) bearing mice. Cantharidin
      treatment caused the appearance of abnormal mitochondrial features which included
      roundish mitochondria with thickened membranes, irregularity in cristae, and
      appearance of small and large size vacuoles in mitochondria of DL cells.
      Cantharidin treatment resulted in a decrease in mitochondrial reduced
      glutathione, succinate dehydrogenase activity, mitochondrial membrane potential,
      and induced apoptosis and necrosis in DL cells. The decrease/release of
      mitochondrial cytochrome c were also observed after cantharidin treatment. Flow
      cytometry-based cell cycle analysis showed a time-dependent accumulation of the
      sub-G0 population of DL cells, thus, confirming the involvement of apoptosis in
      tumor cells in cantharidin-mediated antitumor activity. These finding signify
      that the apoptosis induced by cantharidin in DL cells should involve
      mitochondrial-dependent pathways. It is suggested that these cantharidin-mediated
      changes in mitochondria may play a crucial role in its antitumor activity. 

PMID- 24029498
TI  - Getting bums out of seats.

PMID- 24029500
TI  - Learning to change: coming updates to the CFPC Mainpro(r) program.

PMID- 24029501
TI  - Challenges for rural communities in recruiting and retaining physicians: a
      fictional tale helps examine the issues.

PMID- 24029502
TI  - Generalism: the princess and the pea.

PMID- 24029503
TI  - Adverse health effects of industrial wind turbines.

PMID- 24029505
TI  - Recommendations on screening for high blood pressure in Canadian adults.
AB  - OBJECTIVE: To provide recommendations on screening for hypertension in adults
      aged 18 years and older without previously diagnosed hypertension. QUALITY OF
      EVIDENCE: Evidence was found through a systematic search of MEDLINE, EMBASE, and
      the Cochrane Database of Systematic Reviews (EBM Reviews), from January 1985 to
      September 2011. Study types were limited to randomized controlled trials,
      systematic reviews, and observational studies with control groups. MAIN MESSAGE:
      Three strong recommendations were made based on moderate-quality evidence. It is
      recommended that blood pressure measurement occur at all appropriate primary care
      visits, according to the current techniques described in the Canadian
      Hypertension Education Program recommendations for office and ambulatory blood
      pressure measurement. The Canadian Hypertension Education Program criteria for
      assessment and diagnosis of hypertension should be applied for people found to
      have elevated blood pressure. CONCLUSION: After review of the most recent
      evidence, the Canadian Task Force on Preventive Health Care continues to
      recommend blood pressure measurement during regular physician visits.

PMID- 24029506
TI  - Long-term sequelae of electrical injury.
AB  - OBJECTIVE: To summarize the current evidence-based knowledge about the long-term
      sequelae of injuries from electrical current. QUALITY OF EVIDENCE: MEDLINE was
      searched for English-language articles published in the past 20 years using the
      following search terms: electrical, injuries, wound, trauma, accident, sequelae,
      long-term, follow-up, and aftereffects. For obvious reasons, it is unethical to
      randomly study electrical injury in controlled clinical trials. By necessity,
      this topic is addressed in less-rigorous observational and retrospective work and
      case studies. Therefore, the strength of the literature pertaining to the long
      term sequelae of electrical injury is impaired by the necessity of retrospective
      methods and case studies that typically describe small cohorts. MAIN MESSAGE:
      There are 2 possible consequences of electrical injury: the person either
      survives or dies. For those who survive electrical injury, the immediate
      consequences are usually obvious and often require extensive medical
      intervention. The long-term sequelae of the electrical injury might be more
      subtle, pervasive, and less well defined, but can include neurologic,
      psychological, and physical symptoms. In the field of compensation medicine,
      determining causation and attributing outcome to an injury that might not result
      in objective clinical findings becomes a considerable challenge. CONCLUSION: The
      appearance of these consequences of electrical injury might be substantially
      delayed, with onset 1 to 5 or more years after the electrical injury. This poses
      a problem for patients and health care workers, making it hard to ascribe
      symptoms to a remote injury when they might not arise until well after the
      incident event.

PMID- 24029507
TI  - Antidepressant use during pregnancy: navigating the sea of information.
AB  - QUESTION: When some of my patients who are taking antidepressants learn they are
      pregnant, they become anxious and confront me with the following statement: "I
      need this medication, but have heard so many conflicting stories from my friends
      and on the Internet and in the media that I am not sure if I should continue
      taking it." How do I advise them, as I have also seen conflicting evidence in the
      scientific literature? ANSWER: To date, antidepressants are the most studied
      drugs during pregnancy, with more than 30 000 outcomes examining increased risks
      of adverse effects on exposed infants. The results of the studies can appear to
      be conflicting owing to differing interpretation of statistical analysis and
      subsequent knowledge transfer and translation of the information. However, there
      does not appear to be a clinically significant increased risk of any of the
      adverse outcomes reported in peer-reviewed published studies that would preclude
      a woman from taking a needed antidepressant during pregnancy.

PMID- 24029508
TI  - Caffeinated energy drinks in children.
AB  - QUESTION: A 14-year-old boy came to my office to discuss his frequent consumption
      of energy drinks to enhance his performance at school and while playing soccer.
      What is the recommended use of energy drinks in children and is there any harm in
      consuming them? ANSWER: Energy drinks are beverages with a high concentration of
      caffeine and additional stimulants. They are sold in numerous places and are
      easily accessed by children, adolescents, and young adults. Many reports warn
      about potential adverse effects associated with their consumption, especially in
      combination with alcohol among adolescents, and in combination with stimulant
      medications among children treated for attention deficit hyperactivity disorder.
      Children and adolescents should avoid energy drinks, and health care providers
      should educate youth and their parents about the risks of caffeinated drinks.

PMID- 24029509
TI  - Seizures in palliative care.

PMID- 24029510
TI  - Probiotics for the prevention of Clostridium difficile.

PMID- 24029511
TI  - Dapsone-induced methemoglobinemia: case of the blue lady.

PMID- 24029512
TI  - Pneumatic otoscopy.

PMID- 24029513
TI  - Dermacase. Can you identify this condition? Bullous pemphigoid.

PMID- 24029514
TI  - Physical Activity Line: effective knowledge translation of evidence-based best
      practice in the real-world setting.

PMID- 24029516
TI  - Third time's the charm.

PMID- 24029515
TI  - Use and teaching of pneumatic otoscopy in a family medicine residency program.
AB  - OBJECTIVE: To determine to what extent FPs teach and use pneumatic otoscopy and
      to identify the chief influences on this behaviour. DESIGN: Mixed-methods
      descriptive study conducted between March and May 2011. SETTING: The family
      medicine residency program at Laval University in Quebec city, Que. PARTICIPANTS:
      Directors of the family medicine teaching units (FMTUs), teachers, and residents.
      METHODS: We used questionnaires to assess the availability of pneumatic otoscopy
      equipment in 12 FMTUs, current behaviour and behavioural intention among
      physicians (residents and teachers) to use or teach pneumatic otoscopy, and
      facilitators and barriers to these practices. We also conducted 2 focus groups to
      further explore the facilitators of and barriers to using pneumatic otoscopy. We
      used descriptive statistics for quantitative data, transcribed the qualitative
      material, and performed content analysis. MAIN FINDINGS: Eight of the 12 FMTUs
      reported having pneumatic otoscopy equipment. Four had it in all of their
      consulting rooms, and 2 formally taught it. Nine (4%) of 211 physicians reported
      regular use of pneumatic otoscopy. Mean (SD) intention to teach or use pneumatic
      otoscopy during the next year was low (2.4 [1.0] out of 5). Teachers identified
      improved diagnostic accuracy as the main facilitator both for use and for
      teaching, while residents identified recommendation by practice guidelines as the
      main facilitator for use. All physicians reported lack of availability of
      equipment as the main barrier to use. The main barrier to teaching pneumatic
      otoscopy reported by teachers was that they did not use it themselves. In focus
      groups, themes of consequences, capabilities, and socioprofessional influences
      were most dominant. Residents clearly identified role modeling by teachers as
      facilitating the use of pneumatic otoscopy. CONCLUSION: Pneumatic otoscopy is
      minimally used and taught in the family medicine residency program studied.
      Interventions to increase its use should target identified underlying beliefs and
      facilitators of and barriers to its use and teaching.

PMID- 24029519
TI  - Teaching the essence of family medicine.

PMID- 24029518
TI  - Participatory health research: celebrating smoke-free homes.
AB  - For community engagement to be successful, the interests of the community must be
      taken into account and researchers must become facilitators. Patience is
      required. Meaningful and sustainable relationships that have been developed over
      time promote mutual learning and capacity building among the partners (Elders,
      community members, health care providers, and researchers). In addition,
      community engagement leads to the sharing of available resources (eg, human,
      time, and financial) and to a sustained commitment by the partners. This mutual
      commitment makes future projects easier to develop and complete. Thus, authentic
      transformative health development, informed by participatory health research,
      becomes an ongoing process.

PMID- 24029522
TI  - Mainpro(r): from improvement of knowledge to improvement of performance.

PMID- 24029527
TI  - Shifting into third gear: current options and controversies in third-year
      postgraduate family medicine programs in Canada.
AB  - OBJECTIVE: To summarize current options for postgraduate third-year programs in
      family medicine in Canada and compile current controversies about the expanding
      number of programs available and the trend toward subspecialization in family
      medicine. DESIGN: A literature search was conducted by the Regina Qu'Appelle
      Health Region Library research staff for Canadian family medicine fellowships and
      residency programs using MEDLINE, PubMed, and the Cumulative Index to Nursing and
      Allied Health Literature from the beginning of 2005 to September 1, 2011. All
      available websites for programs offering third-year options were reviewed.
      SETTING: Canadian family medicine residency programs. METHODS: A list of current
      third-year residency programs was generated from the Canadian Post-MD Education
      Registry. In addition, the current Canadian Resident Matching Service website was
      reviewed, along with every program-specific website, for current third-year
      programs offered. MAIN FINDINGS: More than 30 different options for third-year
      residency programs are available, including a number of community-influenced and
      resident-directed enhanced-skills programs. In 2010 to 2011 there were 237
      postgraduate third-year family medicine residents compared with 128 in 2010 to
      2011, an increase of 109 positions. CONCLUSION: Controversies over the benefits
      to the patient population, the practice patterns of third-year residency
      graduates, and the influence of a subspecialty trend against a stated goal of
      comprehensive family medicine continue to exist, while the number of available
      third-year residency options continues to expand.

PMID- 24029528
TI  - Collaboration between family physicians and community pharmacists: opinions of
      graduates in family medicine.
AB  - OBJECTIVE: To ascertain the opinions of graduating family physicians about
      collaboration between family physicians and community pharmacists. DESIGN:
      Anonymous online survey. SETTING: Two French-Canadian university family medicine
      residency programs. PARTICIPANTS: The 2010 and 2011 graduating family physicians
      (N = 343) from the University of Montreal and Laval University in Quebec. MAIN
      OUTCOME MEASURES: Content of written prescriptions; frequency of and reasons for
      consultations with community pharmacists; and graduates' perceptions of sharing
      professional responsibilities with community pharmacists. RESULTS: The response
      rate was 54.2%. Overall, graduates were open to collaborating actively with
      community pharmacists. For example, at least 60% of graduates reported that it
      was important to write on prescriptions about any changes to patients' medication
      and creatinine clearance. Most graduates responded positively to sharing
      responsibility for the adjustment of treatment of patients with certain chronic
      conditions (88.3% for anticoagulation, 64.7% for hypercholesterolemia, 61.2% for
      hypertension, and 60.6% for diabetes) and for the initiation of treatment of
      minor conditions according to a collective prescription (80.6% for traveler's
      diarrhea, 74.1% for juvenile acne, and 73.6% for allergic rhinitis). However,
      such interprofessional collaboration requires that each professional group
      continues to adapt to its roles and responsibilities. CONCLUSION: Family medicine
      graduates are open to actively collaborating with community pharmacists, but they
      have some reservations regarding sharing certain responsibilities. As
      collaborative practices are changing, graduates' opinions should be documented
      once they are actually practising.

PMID- 24029529
TI  - Residents as teachers: survey of Canadian family medicine residents.
AB  - OBJECTIVE: To examine Canadian family medicine residents' perspectives
      surrounding teaching opportunities and mentorship in teaching. DESIGN: A 16
      question online survey. SETTING: Canadian family medicine residency programs.
      PARTICIPANTS: Between May and June 2011, all first- and second-year family
      medicine residents registered in 1 of the 17 Canadian residency programs as of
      September 2010 were invited to participate. A total of 568 of 2266 residents
      responded. MAIN OUTCOME MEASURES: Demographic characteristics, teaching
      opportunities during residency, and resident perceptions about teaching. RESULTS:
      A total of 77.7% of family medicine residents indicated that they were either
      interested or highly interested in teaching as part of their future careers, and
      78.9% of family medicine residents had had opportunities to teach in various
      settings. However, only 60.1% of respondents were aware of programs within
      residency intended to support residents as teachers, and 33.0% of residents had
      been observed during teaching encounters. CONCLUSION: It appears that most
      Canadian family medicine residents have the opportunity to teach during their
      residency training. Many are interested in integrating teaching as part of their
      future career goals. Family medicine residencies should strongly consider
      programs to support and further develop resident teaching skills.

PMID- 24029530
TI  - Knowledge of CanMEDS-Family Medicine roles: survey of Canadian family medicine
      residents.
AB  - OBJECTIVE: This study evaluates the self-perceived awareness of the new CanMEDS
      Family Medicine (CanMEDS-FM) roles by family medicine residents. DESIGN: A 22
      question online survey. SETTING: Canadian family medicine residency programs.
      PARTICIPANTS: All residents enrolled in a Canadian family medicine residency as
      of September 2010 received the survey between May and June 2011. A total of 568
      residents participated. MAIN OUTCOME MEASURES: Survey respondents indicated their
      awareness of, their exposure to, and the perceived importance of the CanMEDS-FM
      roles. RESULTS: The survey response rate was 25.1%. In total, 88.9% (463 of 521)
      of family medicine residents were aware of the CanMEDS-FM roles; there was no
      statistically significant difference in awareness between first- and second-year
      residents. Family medicine expert and communicator were most frequently chosen as
      the most important CanMEDS-FM roles, while manager and scholar were selected the
      least often. Overall, 76.4% of family medicine residents thought that their core
      family medicine teaching was guided by CanMEDS-FM, while 41.8% thought the same
      about off-service rotations. CONCLUSION: It appears that most family medicine
      residents are aware of the CanMEDS-FM roles. While core family medicine training
      and evaluation seem to be grounded in CanMEDS-FM, residency program directors
      should endeavour to ensure that the same principles apply during off-service
      rotations.

PMID- 24029532
TI  - Degradation of naproxen by UV, VUV photolysis and their combination.
AB  - Naproxen is a widely used nonsteroidal anti-inflammatory drug. Recently, this
      medicine was detected both in natural waters (up to 1.5 MUg L(-1)) and in sewage
      treatment plant effluents (up to 5.2 MUg L(-1)). Moreover, naproxen is only
      partly eliminated by classical processes used in sewage treatment plants.
      Therefore, its degradation is of utmost interest. Advanced oxidation processes
      proved to be the most suitable methods for the elimination of persistent organic
      contaminants. In this work ultraviolet (UV, 254 nm), vacuum ultraviolet
      photolysis (VUV, 172 nm) and their combination (UV/VUV, 254/185 nm) were
      investigated. The efficiency of the methods increased in the following order: UV
      < VUV < UV/VUV photolysis. However, VUV irradiation was found to mineralize the
      contaminant molecule most effectively. The chemical structures of three out of
      four aromatic by-products and of some aliphatic carboxylic acids were presumed.
      The effects of dissolved O2 and the initial concentration of naproxen on the
      degradation were also investigated.

PMID- 24029534
TI  - Developing a reporting guideline for social and psychological intervention
      trials.
AB  - Social and psychological interventions are often complex. Understanding
      randomised controlled trials (RCTs) of these complex interventions requires a
      detailed description of the interventions tested and the methods used to evaluate
      them. However, RCT reports often omit, or inadequately report, this information.
      Incomplete and inaccurate reporting hinders the optimal use of research, wastes
      resources and fails to meet ethical obligations to research participants and
      consumers. In this paper, we explain how reporting guidelines have improved the
      quality of reports in medicine, and describe the ongoing development of a new
      reporting guideline for RCTs: CONSORT-SPI (an extension for social and
      psychological interventions). We invite readers to participate in the project by
      visiting our website, in order to help us reach the best-informed consensus on
      these guidelines (http://tinyurl.com/CONSORT-study). 

PMID- 24029533
TI  - HIF-dependent regulation of AKAP12 (gravin) in the control of human vascular
      endothelial function.
AB  - Hypoxia has been widely implicated in many pathological conditions, including
      those associated with inflammation and tumorigenesis. A number of recent studies
      have implicated hypoxia in the control of vasculogenesis and permeability, the
      basis for which is not fully understood. Here we examine the transcriptional
      regulation of angiogenesis and permeability by hypoxia in endothelial cells.
      Guided by a global profiling approach in cultured endothelial cells, these
      studies revealed the selective induction of human gravin (protein kinase A
      anchoring protein 12) by hypoxia. Analysis of the cloned gravin promoter
      identified a functional hypoxia-responsive region including 2 binding sites for
      hypoxia-inducible factor (HIF). Site-directed mutagenesis identified the most
      distal HIF-binding site as essential for the induction of gravin by hypoxia.
      Further studies examining gravin gain and loss of function confirmed strong
      dependence of gravin in control of microvascular endothelial tube formation,
      wherein gravin functions as a "braking" system for angiogenesis. Additional
      studies in confluent endothelia revealed that gravin functionally couples to
      control endothelial barrier function in response to protein kinase A (PKA)
      agonists. Taken together, these results demonstrate transcriptional coordination
      of gravin by HIF-1alpha and amplified PKA-dependent endothelial responses. These
      findings provide an important link between hypoxia and metabolic conditions
      associated with inflammation and angiogenesis.

PMID- 24029535
TI  - Effects of combined pharmacotherapy and psychotherapy for improving work
      functioning in major depressive disorder.
AB  - BACKGROUND: Major depressive disorder is associated with significant impairment
      in occupational functioning and reduced productivity, which represents a large
      part of the overall burden of depression. AIMS: To examine symptom-based and work
      functioning outcomes with combined pharmacotherapy and psychotherapy treatment of
      major depressive disorder. METHOD: Employed patients with a DSM-IV diagnosis of
      major depressive disorder were treated with escitalopram 10-20 mg/day and
      randomised to: (a) telephone-administered cognitive-behavioural therapy
      (telephone CBT) (n = 48); or (b) adherence-reminder telephone calls (n = 51).
      Outcomes included the Montgomery-Asberg Depression Rating Scale (MADRS),
      administered by masked evaluators via telephone, and self-rated work functioning
      scales completed online. (Registered at clinicaltrials.gov: NCT00702598.)
      RESULTS: After 12 weeks, there were no significant between-group differences in
      change in MADRS score or in response/remission rates. However, participants in
      the telephone-CBT group had significantly greater improvement on some measures of
      work functioning than the escitalopram-alone group. CONCLUSIONS: Combined
      treatment with escitalopram and telephone-administered CBT significantly improved
      some self-reported work functioning outcomes, but not symptom-based outcomes,
      compared with escitalopram alone.

PMID- 24029537
TI  - Mental disorders, disability and treatment gap in a protracted refugee setting.
AB  - BACKGROUND: Studies have shown high levels of distress and mental disorder among
      people living in refugee camps, yet none has confirmed diagnosis through clinical
      reappraisal. AIMS: To estimate the prevalence of mental disorders, related
      disability and treatment gap in adult refugees living in the Burj el-Barajneh
      camp. METHOD: Randomly selected participants were screened by household
      representative (n = 748) and individual (n = 315) interviews; clinical
      reappraisal was performed on a subset (n = 194) of 326 selected participants.
      Weighted prevalence estimates and 95% confidence intervals were calculated.
      RESULTS: The prevalence of current mental disorders was 19.4% (95% CI 12.6-26.2);
      depression was the most common diagnosis (8.3%, 95% CI 4.4-12.2) and multiple
      diagnoses were common (42%) among the 88 persons with mental disorder. Lifetime
      prevalence of psychosis was 3.3% (95% CI 1.0-5.5). Mental disorders were
      associated with moderate to severe dysfunction (odds ratio = 8.8, 95% CI 4.5
      17.4). The treatment gap was 96% (95% CI 92-100). CONCLUSIONS: A range of mental
      disorders and associated disability are common in this long-term refugee setting.
      Combined with an important treatment gap, findings support the current consensus
      based policy to prioritise availability of mental health treatment in refugee
      camps, especially for the most severe and disabling conditions.

PMID- 24029536
TI  - Cost-effectiveness of injectable opioid treatment v. oral methadone for chronic
      heroin addiction.
AB  - BACKGROUND: Despite evidence of the effectiveness of injectable opioid treatment
      compared with oral methadone for chronic heroin addiction, the additional cost of
      injectable treatment is considerable, and cost-effectiveness uncertain. AIMS: To
      compare the cost-effectiveness of supervised injectable heroin and injectable
      methadone with optimised oral methadone for chronic refractory heroin addiction.
      METHOD: Multisite, open-label, randomised controlled trial. Outcomes were
      assessed in terms of quality-adjusted life-years (QALYs). Economic perspective
      included health, social services and criminal justice resources. RESULTS:
      Intervention costs over 26 weeks were significantly higher for injectable heroin
      (mean L8995 v. L4674 injectable methadone and L2596 oral methadone; P<0.0001).
      Costs overall were highest for oral methadone (mean L15 805 v. L13 410 injectable
      methadone and L10 945 injectable heroin; P = n.s.) due to higher costs of
      criminal activity. In cost-effectiveness analysis, oral methadone was dominated
      by injectable heroin and injectable methadone (more expensive and less
      effective). At willingness to pay of L30 000 per QALY, there is a higher
      probability of injectable methadone being more cost-effective (80%) than
      injectable heroin. CONCLUSIONS: Injectable opioid treatments are more cost
      effective than optimised oral methadone for chronic refractory heroin addiction.
      The choice between supervised injectable heroin and injectable methadone is less
      clear. There is currently evidence to suggest superior effectiveness of
      injectable heroin but at a cost that policy makers may find unacceptable. Future
      research should consider the use of decision analytic techniques to model
      expected costs and benefits of the treatments over the longer term.

PMID- 24029538
TI  - Impact of patient involvement in mental health research: longitudinal study.
AB  - BACKGROUND: It is deemed good practice to involve patients routinely in research
      but no study has investigated the practical benefits, particularly to successful
      recruitment. AIMS: To identify whether patient involvement is associated with
      study success. METHOD: All studies listed on the Mental Health Research Network
      (MHRN) portfolio database (n = 374) were interrogated using logistic regression,
      ANOVA and Pearson's correlation to identify associations with study
      characteristics, funding bodies and recruitment success. RESULTS: Patient
      involvement increased over time although in some areas of research it was
      limited. Some funders, especially the National Institute for Health Research
      (NIHR), had more associated patient involvement than others. Studies that
      involved patients to a greater extent were more likely to have achieved
      recruitment targets (chi(2) = 4.58, P<0.05), defined as reaching at least 90% of
      the target. CONCLUSIONS: This is the first time associations with study success
      have been identified for patient involvement. Researchers might now consider ways
      to involve patients more comprehensively as this is associated with study
      success. Further research is needed to explore this finding.

PMID- 24029539
TI  - Comparison of short- and long-term dynamic group psychotherapy: randomised
      clinical trial.
AB  - BACKGROUND: There are no randomised clinical trials comparing the outcomes of
      short- with long-term psychodynamic group psychotherapy. AIMS: To compare
      differences in outcome during and after short- and long-term group psychotherapy.
      METHOD: In total, 167 out-patients with mood, anxiety and personality disorders
      were randomised to short- or long-term group therapy (20 or 80 weekly, 90 min
      sessions). Outcome measures were: symptoms (Symptom Checklist 90 - Revised),
      interpersonal problems (Inventory of Interpersonal Problems - Circumplex) and
      psychosocial functioning (Global Assessment of Functioning (GAF) split version:
      GAF-Symptom and GAF-Function). Change over the 3-year study period was assessed
      using linear mixed models. The study was registered in clinicalTrials.gov as
      NCT00521417. RESULTS: Patients in both groups made significant gains. A
      significantly larger symptomatic change over time was found for long-term
      compared with short-term therapy, but no significant differences were detected
      for the three remaining outcome variables. There was a higher number of premature
      terminations in the long-term (33.3%) compared with the short-term group (8.6%).
      CONCLUSIONS: Short- and long-term therapy seem equally effective for typical out
      patients seeking group psychotherapy, except for symptomatic distress.

PMID- 24029540
TI  - A slightly high-normal glucose level is associated with increased arterial
      stiffness in Japanese community-dwelling persons with pre-diabetes.
AB  - Impaired fasting glucose (IFG) in diabetes is a risk factor for arterial
      stiffness and cardiovascular disease (CVD), but the impact of a slightly high
      normal glucose level remains controversial. We investigated whether slightly high
      normal fasting plasma glucose (FPG) was independently associated with arterial
      stiffness in non-diabetic community-dwelling persons. We recruited 114 men aged
      69 +/- 9 years (range 40-89) and 208 women aged 68 +/- 7 years (range 36-84)
      during their annual health examination in a single community. Arterial stiffness
      was evaluated by the mean of the right and left brachial-ankle pulse wave
      velocity (ba-PWV). Age-adjusted ba-PWV increased significantly from the lowest to
      the highest FPG group (p < 0.001). Multiple linear regression analyses for ba-PWV
      revealed that FPG levels (beta=0.154, p < 0.001) were independently and
      significantly associated with ba-PWV. The multivariate-adjusted ba-PWV value of
      the high-normal glucose group (Group 3: 95-100 mg/dL) was significantly higher
      than that of the lowest normal glucose group (Group 1: 52-89 mg/dL) (p=0.021),
      and the ba-PWV value in the IFG group (Group 4: 101-125 mg/dL) was significantly
      higher than those of the normal glucose groups (Group 1: <90 mg/dL; Group 2: 90
      94 mg/dL) (p<0.001 and p=0.009, respectively). Slightly high-normal glucose
      levels were associated with arterial stiffness in Japanese community-dwelling
      persons.

PMID- 24029541
TI  - Single aortic clamping in coronary artery bypass surgery reduces cerebral
      embolism and improves neurocognitive outcomes.
AB  - Aortic manipulation releases embolic material, thereby enhancing the probability
      of adverse neurologic outcomes following coronary artery bypass grafting (CABG).
      We prospectively evaluated 59 patients undergoing CABG. Patients in the single
      (SC, n = 37) and multiple clamp (MC, n = 22) groups were comparable in relation
      to age and operative risk (p > 0.05). Neurocognitive evaluation consisted of the
      Auditory Verbal Learning Test (AVLT), Color Trails Test A, the Grooved Pegboard
      test and the Mini-Mental State Examination. Data acquisition was performed
      preoperatively, early postoperatively and at the 4-month follow-up.
      Intraoperative transcranial Doppler (TCD) monitoring was used to quantify the
      embolic load in relation to different aortic clamping strategies. Preoperative
      neurocognitive results were similar between the groups (p > 0.05). The incidence
      of postoperative delirium was greater in the MC group but this failed to reach
      statistical significance (23% vs 8%, p = 0.14). SC patients had fewer
      embolization signals (270 +/- 181 vs 465 +/- 160, p < 0.0001). Early
      postoperative neurocognitive results were depressed in comparison to preoperative
      values in both groups (p < 0.05 for multiple comparisons). The magnitude of this
      cognitive depression was greater in the MC group (p < 0.05 for multiple
      comparisons). Preoperative levels of neurocognition were restored at follow-up in
      the SC group in all tests except the AVLT. A trend towards improvements in
      neurocognitive performances at follow-up was also observed in the MC group.
      Residual attention, motor skill and memory deficits were, however, documented
      with multiple tests. In conclusion, the embolic burden was significantly lower in
      the SC group. This TCD imaging outcome translated into fewer early cognition
      deficits and superior late restoration of function.

PMID- 24029542
TI  - Warfarin pharmacogenetics: a controlled dose-response study in healthy subjects.
AB  - The aim of this study was to determine how genetic variants contribute to
      warfarin dosing variability when non-genetic factors are controlled. Thirty
      healthy subjects were subjected to a warfarin dosing algorithm with daily
      international normalized ratio (INR) measurements to INR >= 2.0, then off
      warfarin to INR <= 1.2. The primary outcome was the cumulative dose required to
      achieve INR >= 2.0 for 2 consecutive days. CYP2C9 (p=0.004) and VKORC1 (p=0.02)
      variant carriers required lower cumulative doses, and CYP4F2 carriers required
      higher doses (p=0.04). Subjects with variants in both CYP2C9 and VKORC1 required
      fewer days to reach INR >= 2.0 than wild-type subjects or those with variants in
      CYP2C9 or VKORC1 (p=0.01). Genetic contribution to dose variability (~62%) was
      greater than previously reported, suggesting that uncontrolled clinical variables
      influence the effect of these variants. In conclusion, genotype-guided warfarin
      dosing algorithms may rely more on genetic variables in healthier individuals
      than in patients with clinical confounders.

PMID- 24029543
TI  - The prognosis of functional (psychogenic) motor symptoms: a systematic review.
AB  - BACKGROUND: The prognosis of functional (or psychogenic) motor symptoms (weakness
      and movement disorder) has not been systematically reviewed. METHODS: We
      systematically reviewed PubMed for all studies of eight or more patients with
      functional motor symptoms reporting follow-up data longer than 6 months
      (excluding studies reporting specific treatments). We recorded symptom duration,
      physical and psychiatric comorbidity, disability, occupational functioning at
      follow-up and prognostic factors. RESULTS: 24 studies were included. There was
      heterogeneity regarding study size (number of patients (n)=10 491), follow-up
      duration clinical setting and data availability. Most studies (n=15) were
      retrospective. Reported symptom outcome was highly variable. Mean weighted follow
      up duration was 7.4 years (in 13 studies where data was extractable). The mean
      percentage of patients same or worse at follow-up for all studies was 39%, range
      10% to 90%, n=1134. Levels of physical disability and psychological comorbidity
      at follow-up were high. Short duration of symptoms, early diagnosis and high
      satisfaction with care predicted positive outcome in two studies. Gender had no
      effect. Delayed diagnosis and personality disorder were negatively correlated
      with outcome. Prognostic factors that varied between studies included age,
      comorbid anxiety and depression, IQ, educational status, marital status and
      pending litigation. CONCLUSIONS: Existing follow-up studies of functional motor
      symptoms give us some insights regarding outcome and prognostic factors but are
      limited by their largely retrospective and selective nature. Overall, prognosis
      appears unfavourable. The severity and chronicity of functional motor symptoms
      argues for larger prospective studies including multiple prognostic factors at
      baseline in order to better understand their natural history.

PMID- 24029544
TI  - What is the prototype of familial amyloid polyneuropathy?

PMID- 24029545
TI  - Depression in glioma: a primer for clinicians and researchers.
AB  - Depression is one of the leading causes of global disability, and a considerable
      hidden morbidity among patients with glioma. In this narrative review, we
      summarise what is currently known about depression in glioma, the main unanswered
      questions and the types of studies that should be prioritised in order to find
      out. We conclude by calling for a prospective Phase II study of antidepressants
      in depressed glioma patients, to test methodologies for a multicentre randomised
      controlled trial. 

PMID- 24029547
TI  - External validation of the DRAGON score in an elderly Spanish population:
      prediction of stroke prognosis after IV thrombolysis.
AB  - BACKGROUND: Intravenous (i.v.) thrombolysis within 4.5 h of symptom onset has
      proven efficacy in acute ischemic stroke treatment, although half of all outcomes
      are unfavorable. The recently published DRAGON score aims to predict the 3-month
      outcome in stroke patients who have received i.v. alteplase. The purpose of this
      study was an external validation of the results of the DRAGON score in a Spanish
      cohort. METHODS: Patients with acute stroke treated with alteplase were
      prospectively registered in our BasicMar database. We collected demographic
      characteristics, vascular risk factors, the time from stroke onset to treatment,
      baseline serum glucose levels and stroke severity for this population. We then
      reviewed hyperdense cerebral artery signs and signs of early infarct on the
      admission CT scan. We calculated the DRAGON score and used the developers' 3
      month prognosis categories: good [modified Rankin Scale score (mRS) 0-2], poor
      (mRS 3-6) and miserable (mRS 5-6) outcome. Discrimination was tested using the
      area under the receiver operator curve (AUC-ROC). Calibration was assessed by the
      Hosmer-Lemeshow test. RESULTS: Our final cohort of 297 patients was older (median
      age 74 years, IQR 65-80) and had more risk factors and severe strokes [median
      National Institutes of Health Stroke Scale (NIHSS) points 13, IQR 7-19] than the
      original study population. Poor prognosis was observed in 143 (48.1%) patients.
      Higher DRAGON scores were associated with a higher risk of poor prognosis. None
      of our treated stroke patients with a DRAGON score >=8 at admission experienced a
      favorable outcome after 3 months. All DRAGON variables were significantly
      associated with a worse outcome in the multivariate analysis except for onset-to
      treatment time (p = 0.334). Discrimination to predict poor prognosis was very
      good (AUC-ROC 0.84) and the score had good Hosmer-Lemeshow calibration (p =
      0.84). CONCLUSIONS: The DRAGON score is easy to perform and offers a rapid,
      reliable prediction of poor prognosis in acute-stroke patients treated with
      alteplase. This study replicates the original results in a different population.

PMID- 24029549
TI  - Bullying and self-esteem in adolescents from public schools.
AB  - OBJECTIVES: To perform a situational analysis of bullying and self-esteem in
      municipal school units, by estimating the prevalence of bullying, according to
      gender, age, and role in bullying situations; and to identify the level of self
      esteem of students by gender and role in bullying situations and correlate with
      the involvement in bullying situations. METHODS: This was a cross-sectional study
      with 237 students in the ninth grade of middle school from public schools
      participating in the School Health Program in the city of Olinda (PE). The
      questionnaire used in the study was divided into three blocks: a sociodemographic
      block; a block on bullying, validated by Freire, Simao, and Ferreira (2006); and
      a block to assess self-esteem, by Rosenberg (1989). RESULTS: The prevalence of
      bullying was 67.5%. The study population consisted of adolescents, mostly female
      (56.4%), aged 15-19 years (51.3%), of black ethnicity (69.1%). Most students
      lived with four or more people (79.7%) in their family-owned homes (83.8%), which
      had five or more rooms (79.1%). Observing bullying or being bullied were the most
      often reported situations (59.9% and 48.9%, respectively); when the roles of
      bullying are associated with self-esteem in relation to gender, it was observed
      that in the group of victims/aggressors and aggressors (p = 0.006 and 0.044,
      respectively), males had higher statistically significant self-esteem scores when
      compared to females. CONCLUSION: The findings indicate a large number of students
      involved in the several roles of bullying, identifying an association between
      these characteristics and sex/gender and self-esteem of those involved. The
      present study has identified the need for further studies on the nature of the
      event.

PMID- 24029548
TI  - Distinct phenotypes in zebrafish models of human startle disease.
AB  - Startle disease is an inherited neurological disorder that causes affected
      individuals to suffer noise- or touch-induced non-epileptic seizures, excessive
      muscle stiffness and neonatal apnea episodes. Mutations known to cause startle
      disease have been identified in glycine receptor subunit (GLRA1 and GLRB) and
      glycine transporter (SLC6A5) genes, which serve essential functions at
      glycinergic synapses. Despite the significant successes in identifying startle
      disease mutations, many idiopathic cases remain unresolved. Exome sequencing in
      these individuals will identify new candidate genes. To validate these candidate
      disease genes, zebrafish is an ideal choice due to rapid knockdown strategies,
      accessible embryonic stages, and stereotyped behaviors. The only existing
      zebrafish model of startle disease, bandoneon (beo), harbors point mutations in
      glrbb (one of two zebrafish orthologs of human GLRB) that cause compromised
      glycinergic transmission and touch-induced bilateral muscle contractions. In
      order to further develop zebrafish as a model for startle disease, we sought to
      identify common phenotypic outcomes of knocking down zebrafish orthologs of two
      known startle disease genes, GLRA1 and GLRB, using splice site-targeted
      morpholinos. Although both morphants were expected to result in phenotypes
      similar to the zebrafish beo mutant, our direct comparison demonstrated that
      while both glra1 and glrbb morphants exhibited embryonic spasticity, only glrbb
      morphants exhibited bilateral contractions characteristic of beo mutants.
      Likewise, zebrafish over-expressing a dominant startle disease mutation (GlyR
      alpha1(R271Q)) exhibited spasticity but not bilateral contractions. Since GlyR
      betab can interact with GlyR alpha subunits 2-4 in addition to GlyR alpha1, loss
      of the GlyR betab subunit may produce more severe phenotypes by affecting
      multiple GlyR subtypes. Indeed, immunohistochemistry of glra1 morphants suggests
      that in zebrafish, alternate GlyR alpha subunits can compensate for the loss of
      the GlyR alpha1 subunit. To address the potential for interplay among GlyR
      subunits during development, we quantified the expression time-course for genes
      known to be critical to glycinergic synapse function. We found that GlyR alpha2,
      alpha3 and alpha4a are expressed in the correct temporal pattern and could
      compensate for the loss of the GlyR alpha1 subunit. Based on our findings, future
      studies that aim to model candidate startle disease genes in zebrafish should
      include measures of spasticity and synaptic development.

PMID- 24029550
TI  - Respiratory syncytial virus infection as a cause of hospitalization in population
      under 1 year in Colombia.
AB  - OBJECTIVE: to determine the frequency, complications and seasonality at which
      respiratory syncytial virus (RSV) infection of the lower respiratory tract causes
      hospitalization in infants of age 1 year or less in 6 cities of Colombia.
      METHODS: one-year prospective multicentric observational study that included 717
      patients presenting to the emergency department with respiratory symptoms in 6
      cities of Colombia. Hospitalized children were tested for RSV with an
      immunofluorescence rapid test in nasopharyngeal secretions. Descriptive and
      statistical analyses of the population were conducted. RESULTS: the study
      population included 717 patients with a mean age of 3.6 months (SD 3.25), 4:3
      male: female ratio and a positive RSV LRTI prevalence of 30.0% (216 infants/City,
      range 26.0 - 49.0%). Risk factors for RSV LRTI were found in 8.2% of the
      population, of which 28.8% were RSV positive. RSV positive and negative groups
      were compared using a two-tailed t test with 95.0%CI, p < 0.05. No statistically
      significant differences were found. All cities presented specific year trimesters
      in the occurrence of RSV LRTI. CONCLUSIONS: the RSV caused 1 in 3 LRTI
      hospitalizations in the population, with an incidence of 30.0%. This confirms a
      continuous circulation of RSV in Colombia varying by geographic location.

PMID- 24029546
TI  - Placebo-controlled trial of oral laquinimod in multiple sclerosis: MRI evidence
      of an effect on brain tissue damage.
AB  - OBJECTIVE: In Assessment of OraL Laquinimod in PrEventing ProGRession in Multiple
      SclerOsis (ALLEGRO), a phase III study in relapsing-remitting multiple sclerosis
      (RRMS), oral laquinimod slowed disability and brain atrophy progression,
      suggesting laquinimod may reduce tissue damage in MS. MRI techniques sensitive to
      the most destructive aspects of the disease were used to further investigate
      laquinimod's potential effects on inflammation and neurodegeneration. METHODS:
      1106 RRMS patients were randomised 1:1 to receive once-daily oral laquinimod (0.6
      mg) or placebo for 24 months. White matter (WM), grey matter (GM) and thalamic
      fractions were derived at months 0, 12 and 24. Also assessed were evolution of
      gadolinium-enhancing and/or new T2 lesions into permanent black holes (PBH);
      magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT), WM,
      GM and T2 lesions; and N-acetylaspartate/creatine (NAA/Cr) levels in WM. RESULTS:
      Compared with placebo, laquinimod-treated patients showed lower rates of WM at
      months 12 and 24 (p=0.004 and p=0.035) and GM (p=0.004) atrophy at month 12 and a
      trend for less GM atrophy at month 24 (p=0.078). Laquinimod also slowed thalamic
      atrophy at month 12 (p=0.005) and month 24 (p=0.003) and reduced the number of
      PBH at 12 and 24 months evolving from active lesions (all p<0.05). By month 24,
      MTR decreased significantly in NABT (p=0.015), WM (p=0.011) and GM (p=0.034) in
      placebo-treated patients, but not in laquinimod-treated patients. WM NAA/Cr
      tended to increase with laquinimod and decrease with placebo at 24 months
      (p=0.179). CONCLUSIONS: Oral laquinimod may reduce (at least in the initial phase
      of treatment) some of the more destructive pathological processes in RRMS
      patients. TRIAL REGISTRATION: The ALLEGRO trial identifier number with
      clinicaltrials.gov is NCT00509145.

PMID- 24029551
TI  - Association of breakfast intake with cardiometabolic risk factors.
AB  - OBJECTIVE: this study aimed to evaluate the association of breakfast intake with
      cardiometabolic risk factors in a nationally-representative sample of Iranian
      pediatrics. METHODS: the study participants considered of 5,625 school students
      aged 10-18 years, studied in the third survey of the national school-based
      surveillance system (CASPIAN-III). They were classified into three groups based
      on the number of days they ate breakfast: "regular breakfast eater" (6
      7days/week), "often breakfast eater" (3-5days/week), and "seldom breakfast eater"
      (0-2 days/week). Metabolic syndrome (MetS) was defined based on the Adult
      Treatment Panel III (ATP III) criteria modified for the pediatric age group.
      Moreover, high total cholesterol, high low-density lipoprotein cholesterol (LDL
      C) and generalized obesity were included as other cardiometabolic risk factors.
      Multiple logistic regression analyses were used to evaluate the association
      between the breakfast intake category and cardiometabolic risk factors. RESULTS:
      the number of subjects classified as "regular", "often" and "seldom" breakfast
      eaters were 2,653(47.3%), 1,327(23.7%) and 1,624(29.0%), respectively. The
      average of triglycerides (TG), LDL-C, systolic blood pressure (SBP) and body mass
      index (BMI) were higher in the "seldom breakfast eater" group (P for
      trend<0.001), whereas the mean of high-density lipoprotein cholesterol (HDL-C)
      was lower in this group than their other counterparts. Seldom breakfast eaters
      had an increased risk of obesity, elevated TG and LDL-C, as well as low HDL-C
      compared to "regular breakfast eaters". The risk of MetS was significantly
      increased in subjects who seldom ate breakfast (OR 1.96, 95% CI 1.18-3.27).
      CONCLUSIONS: skipping breakfast is associated with increased risk of MetS and
      other cardiometabooic factors in children and adolescents. Promoting the benefit
      of eating breakfast could be a simple and important implication to prevent these
      risk factors.

PMID- 24029552
TI  - A correlative study of hydrogen peroxide accumulation after mercury or copper
      treatment observed in root nodules of Medicago truncatula under light, confocal
      and electron microscopy.
AB  - Heavy metal stress affects both, nodulation and nitrogen fixation of legumes.
      Mercury triggers disturbances in cellular structure and metabolism but its
      influence on ROS generation is poorly understood. Copper is redox active metal
      which in opposition to mercury is an essential micronutrient for plants. Excess
      of copper is cytotoxic, as it participates in ROS generation via Fenton-type
      reaction. The present work describes changes in hydrogen peroxide (H2O2)
      accumulation in response to monthly stress caused by mercury (6 mg/L HgCl2) or
      copper (60 mg/L CuCl2) in root nodules. H2O2 accumulation viewed with a light
      microscopy was detected by the use of diaminobenzidine (DAB). 2',7'
      Dichlorofluorescein diacetate (H2DCF-DA) was used as a probe for the
      intracellular localization of H2O2 with a confocal laser scanning system. H2O2
      detection under transmission electron microscopy was performed by the use of
      cerium method. Histochemical localization and light and confocal microscopy
      investigations revealed that under Hg or Cu treatments distinct amount of H2O2
      accumulated mainly in the interzone and nitrogen-fixing zone. Under normal
      conditions H2O2 accumulated predominantly in the interzone. Electron microscopy
      observations showed H2O2 accumulation under Hg or Cu- treatments around
      peribacteroid membranes of mature symbiosomes located within nitrogen-fixing
      zone. It should be underlined that under normal conditions H2O2 was not detected
      at the peribacteroid membranes. The main result of our observations is increased
      accumulation of H2O2 in response to mercury and copper treatments at the
      peribacteroidal membranes, to our knowledge shown for the first time. Therefore,
      our results revealed that an overproduction of H2O2 in response to copper or
      mercury-treatment may account for lowering of nitrogen fixation rates in heavy
      metal affected root nodules.

PMID- 24029553
TI  - Quantification of the 5-lipoxygenase inhibitor zileuton in human plasma using
      high performance liquid chromatography-tandem mass spectrometry.
AB  - Zileuton is an orally active, selective inhibitor of 5-lipoxygenase, which
      catalyzes the first step in the conversion of arachadonic acid into leukotrienes.
      Given the important role of leukotrienes in inflammation and cell signaling,
      multiple studies have investigated the efficacy of zileuton in the treatment of
      human disease. Examples of disease targets include asthma, ulcerative colitis,
      rheumatoid arthritis, and more recently, acne, ischemic/reperfusion injury,
      inflammatory pain, and sickle cell anemia. Zileuton is currently approved for the
      prophylaxis and chronic treatment of asthma. We report the development and
      validation of a sensitive and specific liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) assay for the quantification of zileuton in human EDTA
      plasma. The range of reliable response was 3.05-20,000ng/mL in human plasma. The
      calibration curves had a correlation coefficient of r(2)>0.99. The intra-day
      precision was 3.4-5.3%. The inter-day precision ranged from 4.5% to 7.3% and
      inter-day accuracy from 100% to 107%. No matrix interferences, ion
      suppression/enhancement, or carry-over was observed. The assay met all predefined
      acceptance criteria and was subsequently employed to measure plasma zileuton
      concentrations in a clinical trial. 

PMID- 24029554
TI  - Determination of Prostaglandin E1 in dog plasma using liquid chromatography
      tandem mass spectrometry and its application to a pharmacokinetic study.
AB  - The determination of Prostaglandin (PG) E1 in plasma is challenged by its low
      concentration (pg/mL) and endogenous interference. An LC-MS/MS method for the
      determination of PGE1 in dog plasma has been developed and validated. Plasma
      being sampled at 4 degrees C and treated with indomethacin effectively inhibited
      interferents synthesized post-sampling. Samples were subjected to one-step
      extraction and separated by reversed phase HPLC with a short cycle time of 3min.
      An LLOQ of 10pg/mL was achieved with 500MUl plasma. The method was applied to a
      pharmacokinetic study in beagle dogs involving an intravenous infusion of
      3.2MUg/kg PGE1. The half-life was recovered at 7min. The simple, sensitive and
      rapid method was suitable to be applied to pharmacokinetic studies of PGE1 at
      clinically relevant doses. 

PMID- 24029555
TI  - Global gas chromatography/time-of-flight mass spectrometry (GC/TOFMS)-based
      metabonomic profiling of lyophilized human feces.
AB  - Gas chromatography mass spectrometry (GC/MS)-based fecal metabonomics represents
      a powerful systems biology approach for elucidating metabolic biomarkers of lower
      gastrointestinal tract (GIT) diseases. Unlike metabolic profiling of fecal water,
      the profiling of complete fecal material remains under-explored. Here, a gas
      chromatography/time-of-flight mass spectrometry (GC/TOFMS) method was developed
      and validated for the global metabonomic profiling of human feces. Fecal and
      fecal water metabotypes were also profiled and compared. Additionally, the
      unclear influence of blood in stool on the fecal metabotype was investigated
      unprecedentedly. Eighty milligram of lyophilized feces was ultrasonicated with
      1mL of methanol:water (8:2) for 30min, followed by centrifugation, drying of
      supernatant, oximation and trimethylsilylation for 45min. Lyophilized feces
      demonstrated a more comprehensive metabolic coverage than fecal water, based on
      the number of chromatographic peaks. Principal component analysis (PCA) indicated
      occult blood (1mgHb/g feces) exerted a negligible effect on the fecal metabotype.
      Conversely, a unique metabotype related to feces spiked with gross blood
      (100mgHb/g feces) was revealed (PCA, R(2)X=0.837, Q(2)=0.794), confirming the
      potential confounding effect of gross GIT bleeding on the fecal metabotype. This
      pertinent finding highlights the importance of prudent interpretation of fecal
      metabonomic data, particularly in GIT diseases where bleeding is prevalent. 

PMID- 24029557
TI  - Muscle strength and physical activity are associated with self-rated health in an
      adult Danish population.
AB  - OBJECTIVE: To describe associations of muscle strength, physical activity and
      self-rated health. METHOD: Isometric muscle strength by maximal handgrip strength
      (HGS) or muscle strength by 30s repeated chair stand test (30s-CS) was combined
      with leisure time physical activity. Using logistic regression odds ratio was
      calculated for good self-rated health according to the combined associations
      among 16,539 participants (59.7% women), mean age 51.9 (SD: 13.8) years, from a
      cross-sectional study in Denmark 2007-2008. RESULTS: Good self-rated health was
      positively associated with higher levels of physical activity and greater muscle
      strength. Regarding HGS the highest OR for good self-rated health was in the
      moderate/vigorous physically active participants with high HGS (OR=6.84, 95% CI:
      4.85-9.65 and OR=7.34, 95% CI: 5.42-9.96 for men and women, respectively).
      Similarly the highest OR for good self-rated health was in the moderate/vigorous
      physically active participants with high scores in the 30s-CS test (6.06, 95% CI:
      4.32-8.50 and 13.38, 95% CI: 9.59-18.67 for men and women, respectively). The
      reference groups were sedentary participants with low strength (HGS or 30s-CS).
      CONCLUSION: The combined score for physical activity level with either HGS or 30s
      CS was strongly positively associated with self-related health.

PMID- 24029556
TI  - Uptake and positive predictive value of fecal occult blood tests: A randomized
      controlled trial.
AB  - OBJECTIVE: The aim of this study is to compare the uptake of three mailed high
      sensitivity fecal occult blood tests (FOBTs). METHODS: We conducted a parallel 3
      arm randomized controlled trial in an integrated healthcare delivery system in
      Washington State. From January 2010 through February 2011, automated data were
      used to identify potentially eligible patients aged 50-74 due for colorectal
      cancer screening. Participants were mailed one of three FOBT kits (1-sample OC
      Auto(r) fecal immunochemical test [FIT], 2-sample InSure(r) FIT, or 3-sample
      guaiac Hemoccult SENSA(r)), instructions, and a postage-paid return envelope. We
      performed a modified intent-to-treat analysis with return of any FOBT within 6
      months of randomization as the primary outcome. RESULTS: Of the 9922 people
      invited, 2873 returned surveys, 2263 were randomized, and 2234 were analyzed.
      FOBTs were returned by 1431 participants. At 6 months post-randomization, the
      proportions screened by any FOBT were 0.69 (95% confidence interval [CI] 0.66
      0.72) for the OC-Auto arm, 0.64 (95% CI: 0.61-0.68) for the InSure arm, and 0.61
      (95% CI: 0.58-0.65) for the Hemoccult SENSA arm (P<0.001 for any difference).
      Pairwise comparisons showed significant differences between the OC-Auto group and
      each of the other groups after correction for multiple comparisons. CONCLUSION:
      Uptake of mailed FOBT kits varies by kit type.

PMID- 24029558
TI  - Association between documented family history of cancer and screening for breast
      and colorectal cancer.
AB  - BACKGROUND: Previous research on ascertainment of cancer family history and
      cancer screening has been conducted in urban settings. PURPOSE: To examine
      whether documented family history of breast or colorectal cancer is associated
      with breast or colorectal cancer screening. METHODS: Medical record reviews were
      conducted on 3433 patients aged 55 and older from four primary care practices in
      two rural Oregon communities. Data collected included patient demographic and
      risk information, including any documentation of family history of breast or
      colorectal cancer, and receipt of screening for these cancers. RESULTS: A
      positive breast cancer family history was associated with an increased likelihood
      of being up-to-date for mammography screening (OR 2.09, 95% CI 1.45-3.00 relative
      to a recorded negative history). A positive family history for colorectal cancer
      was associated with an increased likelihood of being up-to-date with colorectal
      cancer screening according to U.S. Preventive Services Task Force low risk
      guidelines for males (OR 2.89, 95% CI 1.15-7.29) and females (OR 2.47, 95% CI
      1.32-4.64) relative to a recorded negative family history. The absence of any
      recorded family cancer history was associated with a decreased likelihood of
      being up-to-date for mammography screening (OR 0.70, 95% CI 0.56-0.88 relative to
      recorded negative history) or for colorectal cancer screening (OR 0.75, 95% CI
      0.60-0.96 in females, OR 0.68, 95% CI 0.53-0.88 in males relative to recorded
      negative history). CONCLUSION: Further research is needed to determine if
      establishing routines to document family history of cancer would improve
      appropriate use of cancer screening.

PMID- 24029559
TI  - School-based mindfulness instruction for urban male youth: a small randomized
      controlled trial.
AB  - OBJECTIVES: Mindfulness-based stress reduction (MBSR) has been shown to improve
      mental health and reduce stress in a variety of adult populations. Here, we
      explore the effects of a school-based MBSR program for young urban males.
      PARTICIPANTS AND METHODS: In fall 2009, 7th and 8th graders at a small school for
      low-income urban boys were randomly assigned to 12-session programs of MBSR or
      health education (Healthy Topics-HT). Data were collected at baseline, post
      program, and three-month follow-up on psychological functioning; sleep; and
      salivary cortisol, a physiologic measure of stress. RESULTS: Forty-one (22 MBSR
      and 19 HT) of the 42 eligible boys participated, of whom 95% were African
      American, with a mean age of 12.5 years. Following the programs, MBSR boys had
      less anxiety (p=0.01), less rumination (p=0.02), and showed a trend for less
      negative coping (p=0.06) than HT boys. Comparing baseline with post-program,
      cortisol levels increased during the academic terms for HT participants at a
      trend level (p=0.07) but remained constant for MBSR participants (p=0.33).
      CONCLUSIONS: In this study, MBSR participants showed less anxiety, improved
      coping, and a possible attenuation of cortisol response to academic stress, when
      compared with HT participants. These results suggest that MBSR improves
      psychological functioning among urban male youth.

PMID- 24029560
TI  - Physical activity-friendly neighbourhood among older adults from a medium size
      urban setting in Southern Europe.
AB  - OBJECTIVE: In this cross-sectional study, we examined the relationship between
      socio-environmental characteristics of neighborhood of residence and the
      frequency of leisure-time physical activity (LTPA) among older adults from Porto
      (Portugal). METHOD: Data from EpiPorto - a prospective adult cohort study from
      Porto (Portugal) - were used. Only adults aged >= 65 at baseline (1999-2003) were
      included (n=580). We used a Geographic Information System to objectively measure
      the neighborhood characteristics and Generalized Additive Models to estimate
      their effect on participation in LTPA (none vs. some reported) and frequency of
      LTPA (min/day). RESULTS: 62% of the participants reported no LTPA. Active elderly
      spent on average 38 (women) and 67 (men) minutes per day exercising. Neighborhood
      characteristics were unrelated to whether older people exercised or not. However,
      among active individuals, distance to the nearest destination (beta=-0.154,
      p=0.016), in women, and distance to the nearest park, in men (-0.030, 0.050),
      were predictors of LTPA frequency. CONCLUSION: There was almost no association
      between neighborhood characteristics and whether older adults engaged in LTPA or
      not, but among those that did engage, neighborhood characteristics were
      associated with increased frequency of LTPA. The promotion of well distributed
      destinations and parks might improve physical activity levels among the elderly.

PMID- 24029561
TI  - Longitudinal changes in clinical outcomes in older patients with asthma, COPD and
      asthma-COPD overlap syndrome.
AB  - BACKGROUND: The progression of obstructive airway diseases (OADs) including
      asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap
      syndrome in older adults is not well understood. OBJECTIVE: To examine the
      prognosis of OADs and to identify potential determinants for longitudinal changes
      in clinical outcomes. METHODS: We consecutively recruited 99 older adults (>55
      years) with OADs who underwent a multidimensional assessment at baseline and 4
      years which involved spirometry, 6-min walk distance (6MWD), assessments of
      health status (Saint George's Respiratory Questionnaire, SGRQ), comorbidity, and
      serum and sputum biomarkers. All-cause mortality and respiratory hospitalisation
      during the follow-up period were recorded. Clinical outcomes were compared
      between basal and final visits, and changes in clinical outcomes were compared
      among asthma, COPD and asthma-COPD overlap groups. Associations between clinical
      parameters, biomarkers and prognosis were examined. RESULTS: After a median
      follow-up of 4.2 years, outcome data were available for 75 (75.8%) patients.
      There were 16 (16.2%) deaths. The BODE index predicted all-cause mortality in
      older people with OADs. While spirometry, 6MWD and SGRQ deteriorated
      significantly over the 4 years, there was significant heterogeneity in the
      longitudinal changes in these clinical outcomes. Participants with COPD had a
      significant decline in FEV1 (p = 0.003), SGRQ (p = 0.030) and 6MWD [decline of
      75.5 (93.4) m, p = 0.024]. The change in 6MWD was lower in the asthma-COPD
      overlap group. Airflow reversibility was associated with a reduced decline in
      6MWD. CONCLUSION: COPD patients had a poor prognosis compared with asthma and
      asthma-COPD overlap patients. The BODE index is a useful prognostic indicator in
      older adults with OADs. Both airway disease diagnosis and BODE index warrant
      specific attention in clinical practice.

PMID- 24029562
TI  - Solution processable multi-channel ZnO nanowire field-effect transistors with
      organic gate dielectric.
AB  - The present work focuses on nanowire (NW) applications as semiconducting elements
      in solution processable field-effect transistors (FETs) targeting large-area low
      cost electronics. We address one of the main challenges related to NW deposition
      and alignment by using dielectrophoresis (DEP) to select multiple ZnO nanowires
      with the correct length, and to attract, orientate and position them in
      predefined substrate locations. High-performance top-gate ZnO NW FETs are
      demonstrated on glass substrates with organic gate dielectric layers and surround
      source-drain contacts. Such devices are hybrids, in which inorganic multiple
      single-crystal ZnO NWs and organic gate dielectric are synergic in a single
      system. Current-voltage (I-V) measurements of a representative hybrid device
      demonstrate excellent device performance with high on/off ratio of ~10(7), steep
      subthreshold swing (s-s) of ~400 mV/dec and high electron mobility of ~35 cm(2)
      V(-1) s(-1) in N2 ambient. Stable device operation is demonstrated after 3 months
      of air exposure, where similar device parameters are extracted including on/off
      ratio of ~4 * 10(6), s-s ~500 mV/dec and field-effect mobility of ~28 cm(2) V(-1)
      s(-1). These results demonstrate that DEP can be used to assemble multiples of
      NWs from solvent formulations to enable low-temperature hybrid transistor
      fabrication for large-area inexpensive electronics.

PMID- 24029563
TI  - [The transformation of the basic mode for cancer treatment-from destructive
      strategy to constructive strategy].

PMID- 24029564
TI  - [The compared study in detecting the recurrence and metastases of breast cancer
      patients post treatment between (18)F-FDG PET/CT and conventional workup].
AB  - OBJECTIVE: This study is to investigate the clinical role of (18)F-FDG PET/CT in
      detecting the recurrence and metastases of patients with breast cancer post
      treatment, compared to the conventional imaging technology, such as CT, MRI, and
      ultrasound. METHODS: The reports of FDG PET/CT whole body scans and conventional
      imaging technology, such as CT, MRI, and ultrasound, performed from Jan to Aug
      2011 on 70 patients with breast cancer post treatment were retrospectively
      reviewed.The accuracy, sensitivity, specificity, positive predictive value (PPV)
      and negative predictive value (NPV) of 2 groups in detecting the recurrence and
      metastases were calculated and compared. RESULTS: The accuracy, sensitivity,
      specificity, PPV and NPV of FDG PET/CT were 84.3%, 95.6%, 64.0%, 82.7% and
      88.9%.The conventional imaging technology was 70.0%, 68.9%, 72.0%, 81.6% and
      56.3% respectively.FDG PET/CT had altered the medical management of 20% of
      patients and detected 3 second primary malignancies. CONCLUSION: FDG PET/CT is
      superior to conventional imaging in detecting the recurrence and metastases of
      patients with breast cancer post therapy.

PMID- 24029565
TI  - [Preoperative evaluation of vascular involvement and general resectability of
      pancreatic carcinoma by using 64-slice spiral computed tomographical
      angiography].
AB  - OBJECTIVE: To assess for preoperative evaluation of 64-slice spiral computed
      tomographical angiography (64-SCTA) to predict vascular involvement and general
      resectability of pancreatic malignant tumors. METHODS: The material of 64-SCTA in
      34 cases were retrospectively analyzed. Preoperative imaging findings were
      correlated with intraoperative and histopathologic results. RESULTS: For the
      arterial tumor invasion based on 64-SCTA findings, 1 grade was in 8 cases; 2
      grade, 6 cases; 3 grade, 8 cases; 4 grade, 10 cases;5 grade, 2 cases.Regarding
      respectability, the sensitivity, specificity, accuracy, positive predictive value
      (PPV), negative predictive value (NPV) were 92.9%, 95.0%,94.1%, 92.9%, 95.0%.
      Kappa value was 0.879 (P < 0.01). Receiver operator characteristic (ROC) analysis
      revealed an area under the curve (AUC) of 0.943 (P < 0.01). For the venous tumor
      infiltration, 1 grade was in 0 case; 2 grade, 6 cases; 3 grade, 6 cases; 4 grade,
      13 cases; 5 grade, 9 cases. Regarding respectability, these values for those
      tumors with vein invasion were 78.6%, 95.0%, 88.2%, 91.7%, 86.4%. Kappa value was
      0.752 (P < 0.01). ROC analysis showed an AUC of 0.927 (P < 0.01). CONCLUSION: 64
      SCTA can provide reliable information for vascular involvement and general
      resectability of pancreatic malignant tumors. 64-SCTA has high value in clinical
      application.

PMID- 24029566
TI  - [Noninvasive imaging of vulnerable plaques and thromboses with PET/CT complex
      imaging technique].
AB  - OBJECTIVE: To investigate the feasibility of identifying the vulnerable plaque
      and predicting plague rupture and thrombus using by positron emission
      tomography/computed tomography angiography (PET/CTA). METHODS: Twenty-eight male
      New Zealand white rabbits were fed with hyper-lipid diet for 2 weeks before the
      balloon injury of the abdominal aorta.Then these rabbit were intermittently fed
      with hyper-lipid diet for 14 weeks, in order to trigger pharmaceutic the plague
      rupture and thrombus. PET/CTA scans of abdominal aorta were performed before and
      after the drug triggering, FDG uptake (standardized uptake value, SUV) was
      measured. Rabbits were euthanized to obtain data of pathology and histology. The
      parameters obtained by PET/CTA, pathology and histology were compared and the
      correlations were performed. RESULTS: The thrombosis was identified in 13 of 20
      rabbits.Before the drug triggering, (18)F-FDG mean standardized uptake value
      (SUVmean) was higher in thrombotic arterial segments (defined as vulnerable
      plaque) (1.10 +/- 0.19 vs 0.77 +/- 0.11,P = 0.000); after the drug triggering,
      SUVmean was higher in thrombotic arterial segments, too (1.15 +/- 0.26 vs 0.85 +/
      0.17, P = 0.000). We use the ROC curve for SUVmean to predict plaque rupture and
      thrombosis. The area under the curve (AUC) was 0.898 (P = 0.000). The cutoff
      value was 0.882. CONCLUSIONS: Our findings indicated that (18)F-FDG PET/CTA, as a
      noninvasive imaging method, could be used to identify vulnerable plaques and
      predict thrombosis events.

PMID- 24029567
TI  - [The characteristics of high density lipoprotein cholesterol and the relationship
      between high density lipoprotein cholesterol and the severity of coronary artery
      lesions in young men with acute myocardial infarction].
AB  - OBJECTIVE: To investigate the characteristics of high density lipoprotein
      cholesterol and the relationship between high density lipoprotein cholesterol and
      the severity of coronary artery lesions in young men with acute myocardial
      infarction (AMI). METHODS: We retrospectively studied 278 young men with acute
      myocardial infarction and compared with 208 non-CHD young men, 137 old men with
      AMI. All patients were admitted to hospital from Jan 2009 to Dec 2011 and
      undergone coronary angiography, and the clinic and coronary angiographic features
      were assessed.According to the result of coronary angiography, the patients were
      divided into three groups:the single, double and triple vessel lesions. The
      relation between systolic body mass index (BMI), hemoglobin (Hb), serum uric acid
      (UA), total cholesterol(TC), triglyceride (TG), high density lipoprotein
      cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), smoking
      history, essential hypertension, type 2 diabetes mellitus, familial history of
      early coronary artery disease with acute myocardial infarction and severity of
      coronary artery disease are observed.And observe the characteristics of HDL-C in
      the obesity group and the smoking group in young men based on body mass index and
      smoking history. RESULTS: (1) In young men with AMI group, the HDL-C levels was
      significantly lower than those in non-CHD young men group((1.00 +/- 0.28) mmol/L
      vs (1.05 +/- 0.23) mmol/L, P < 0.05).In young men with AMI group, the HDL-C
      levels was significantly lower than those in old men group with AMI ((1.00 +/-
      0.28) mmol/L vs (1.07 +/- 0.30) mmol/L, P < 0.05);the HDL-C level in young AMI
      men with smoking history was significantly lower than those in young AMI men
      without smoking history ((0.98 +/- 0.25) mmol/L vs (1.09 +/- 0.40) mmol/L, P <
      0.05);the HDL-C level in normal weight group is significantly higher than those
      in overweight and obesity groups in young AMI men ((1.30 +/- 0.55) mmol/L vs
      (0.99 +/- 0.22) mmol/L, (0.98 +/- 0.29) mmol/L, P < 0.05). (2)The HDL-C level in
      the single lesions group was significantly lower than those in the double and
      triple vessel lesions groups ((1.06 +/- 0.29) mmol/L vs (0.92 +/- 0.20) mmol/L,
      (0.91 +/- 0.26) mmol/L, P < 0.05). (3) Applying Logistic regression analysis,
      type 2 diabetes mellitus (OR = 35.784), essential hypertension (OR = 7.782),
      familial history of early coronary artery disease (OR = 4.613), low density
      lipoprotein cholesterol (OR = 2.496), smoking history (OR = 2.241), hemoglobin
      (OR = 1.042) and serum uric acid (OR = 1.005) are independent risk factors (P <
      0.05) for young men with AMI, while high density lipoprotein cholesterol (OR =
      0.147, P < 0.05) is a protective factor; low density lipoprotein cholesterol (OR
      = 2.095) and essential hypertension (OR = 1.042) are independent risk factors (P
      < 0.05) for young men with multiple vessel lesions in AMI, while high density
      lipoprotein cholesterol (OR = 0.071, P < 0.05) is a protective factor.
      CONCLUSION: High density lipoprotein cholesterol are protective factors for young
      men with AMI and multiple vessel lesions in young men with AMI.

PMID- 24029568
TI  - [Pathogenic factors and prognosis of non cardiac inpatients with acute myocardial
      infarction].
AB  - OBJECTIVE: To collect the clinical data of non-cardiac inpatients with coronary
      heart disease risk factors and analyze the pathogenic factors and prognosis
      features of these inpatients with acute myocardial infarction. METHODS:
      Retrospective analyses were performed for 650 cases of consecutive non-cardiac
      inpatients with coronary heart disease risk factors at Tianjin Union Medical
      Center between January 2009 and January 2012.They were divided into non
      myocardial infarction (UnAMI, n = 551) and myocardial infarction groups (AMI, n =
      99). Firstly the method of single factor analysis was employed to screen some
      significant influencing factors of acute myocardial infarction.Secondly
      multivariate Logistic regression analysis was performed to analyze the risk
      factors associated with the onset of AMI. Also the cardiovascular death event
      rates during hospitalization were compared between two groups. Cox regression
      analysis was performed to analyze independent risk factors for cardiovascular
      death of two group during hospitalization. RESULTS: (1) The significant
      influencing factors of AMI included total cholesterol (TC), low-density
      lipoprotein (LDL), advanced age, discontinuation of antiplatelet drug, recent
      episodes of angina above II grade, arrhythmia, 5 years of PCI or CABG history,
      blood glucose control or not, cardiac dysfunction (NYHA II-IV), dehydration,
      severe inflammatory response, infection, peroperative period, emergency operation
      and without cardiological consultation. (2) Multivariate Logistic regression
      analysis showed that LDL (OR (odds ratio): 2.047, 95% CI (confidence interval):
      1.066-3.930, P = 0.031), discontinuation of antiplatelet drug therapy (OR:15.213,
      95% CI: 5.746-40.281, P = 0.000), recent episodes of angina above II grade (OR:
      1.990, 95%CI: 1.155-3.430, P = 0.013), glucose non-control (OR: 2.991, 95%
      CI:1.485-6.026, P = 0.002), advanced age (OR: 2.499, 95% CI: 1.299-4.808, P =
      0.006), severe inflammation (OR:4.425, 95% CI: 2.984-6.561, P = 0.000), infection
      (OR:2.405, 95% CI: 1.058-5.464, P = 0.036), emergency operation (OR:4.365, 95%
      CI: 1.580-12.060, P = 0.004) were all AMI-related occurring factors. And
      cardiologic consultation (OR: 0.011, 95% CI:0.003-0.040, P = 0.000) was a
      favorable factors to reduce AMI; (3) AMI group during hospitalization for
      cardiovascular death event rate was higher than the UnAMI group; (4) Advanced age
      (beta = 0.776, OR = 0.460, 95% CI: 0.217-0.974, P = 0.042) and without
      consultation of cardiology department (beta = 1.366, OR = 3.918, 95% CI: 1.549
      9.912, P = 0.004) were cardiovascular death independent risk factors. CONCLUSION:
      (1) Non cardiac inpatients during hospitalization LDL, discontinuation
      antiplatelet drug therapy, recent episodes of angina above II grade, blood sugar
      non-control, advanced age, severe inflammatory response, infection and without
      cardiologic consultations were significant risk factors for AMI. (2) The
      treatment of Department of Cardiology specialist for non cardiac inpatients with
      coronary heart disease risk factors to improve the prognosis of them.

PMID- 24029569
TI  - [Effects of thoracic endovascular repair in patients of type B aortic
      dissection].
AB  - OBJECTIVE: To retrospectively evaluate early and mid-term results of thoracic
      endovascular repair (TEVAR) of type B aortic dissection by the second generation
      of stent graft. METHODS: From January 2009 to January 2013, 383 acute, 43 sub
      acute and 152 chronic patients with type B aortic dissection underwent TEVAR in
      our aortic center. The mean follow-up period was (27 +/- 14) months. All clinical
      data were analyzed with SPSS 17.0. RESULTS: The 30-day mortality and morbidity
      were 0.35% and 1.2% respectively. The mid-term mortality and morbidity were 0.35%
      and 5.5%. Serious complications included retrograde type A dissection (n = 3),
      new tear at the distal end of stent (n = 26), endoleak (n = 3) and paraplegia (n
      = 0). The retreatment rate was 5.2% ( 6 patients were transformed to open
      operation and 24 patients underwent re-intervention). CONCLUSIONS: The early and
      mid-term results of thoracic endovascular repair (TEVAR) of type B aortic
      dissection by the second generation of stent graft showed lower mortality, no
      paraplegia and significant reduced endoleaks in comparison with the first
      generation stent graft. The new distal tear caused by the stent graft became the
      major complication. The design of the stent graft still need improvement.

PMID- 24029570
TI  - [Correlations between serum hypoxia inducible factor-1alpha, vascular endothelial
      growth factor and computed tomography perfusion imaging at pre-and post-TACE in
      patients with primary hepatic carcinoma].
AB  - OBJECTIVE: To explore the correlations between the serum levels of hypoxia
      inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF)
      and computed tomography (CT) perfusion parameters at pre- and post-transcatheter
      arterial chemoembolization (TACE) in patients with primary hepatic carcinoma
      (PHC). METHODS: A total of 22 PHC patients were recruited.Their serum levels of
      HIF-1alpha and VEGF were measured and CT perfusion imaging (CTPI) was performed
      at Day 1 pre- and Days 32-40 post-TACE to compare and analyze the relevance of
      the changes of serum levels of HIF-1alpha, VEGF, tumor's hepatic artery perfusion
      (HAP), portal vein perfusion (PVP) and hepatic artery perfusion index (HPI) at
      pre- and post-TACE. RESULTS: They were divided into stable and tumor
      residual/recurrent groups according to the efficacy of TACE. No significant
      differences existed between two groups with respects to serum levels of HIF
      1alpha, VEGF, tumor's HAP, PVP and HPI pre-TACE. The serum levels of HIF-1alpha
      and VEGF decreased in stable group and there was significant difference in serum
      level of VEGF at Days 32-40 post-TACE (P < 0.05). There was no perfusion signal
      of HAP or PVP in tumor tissue.The serum levels of HIF-1alpha and VEGF were
      significantly higher while HAP and HPI were significantly lower than that pre
      TACE in tumor residual/recurrent group and had statistical significance (P <
      0.05), but PVP had no change.Positive correlations existed between serum levels
      of HIF-1alpha, VEGF and tumor's HAP, HPI at 32-40 days post-TACE. CONCLUSION:
      Serum levels of HIF-1alpha and VEGF may indirectly reflect the status of
      neovascularization and CTPI acts as the intuitive and quantitative responses of
      hemodynamic changes at post-TACE.Positive correlations exist between serum levels
      of HIF-1alpha, VEGF, HAP and HPI. In short, a combination of serum levels of HIF
      1alpha, VEGF and CTPI contributes to the efficacy evaluation of TACE and has
      great reference significance of determining timing of a second therapy.

PMID- 24029571
TI  - [Metastatic characteristics of lymph node in supraclavicular zone and
      radiotherapy target volume for limited-stage small cell lung cancer].
AB  - OBJECTIVE: To explore the reasonable radiotherapy range by analyzing the
      characteristics of supraclavicular lymph node metastasis in limited-stage small
      cell lung cancer (LS-SCLC). METHODS: From January 2005 to December 2011, patients
      of LS-SCLC were reviewed. Supraclavicular zone was further divided into five
      subgroups including para-recurrent laryngeal nerve (region I and region II ),
      para-internal jugular vein (region III ), supraclavicular region (region IV), as
      well as the other regions except for the mentioned above (region V). The
      characteristics of the lymph nodes in each region were analyzed. RESULTS: The
      supraclavicular lymph node metastasis was found in 60 patients, with a positive
      rate of 34.5%. In multivariate Logistic regression analysis,intra-thoracic lymph
      node metastasis in the lymph node stations of level 2 and 3 were found to be the
      risk factors of supraclavicular lymph node metastasis (P = 0.006,P = 0.000). Our
      data suggests that the frequencies of metastasis in region I and III were much
      higher than those in the other areas.Among the sixty patients with
      supraclavicular lymph node metastasis, 95.0% were found at region I or III while
      the incidence of skip metastasis was only 5.0%. CONCLUSIONS: It is advisable to
      contain the bilateral supraclavicular nodes in patients with mediastinal lymph
      nodes metastasis to the level 2 or 3 for elective radiation target volume.The
      clinical target volume (CTV) exterior margin containing the outer margin of
      internal jugular vein may be suitable.

PMID- 24029572
TI  - [Comparative a nimble of monitoring indicator, explore the superiority about
      Supreme dual-chamber laryngeal mask used for cesarean section anesthesia].
AB  - OBJECTIVE: Explore the feasibility and superiority about Supreme double-lumen
      laryngeal mask airway for cesarean section anesthesia. METHODS: From March 2011
      to March 2012, a total of 300 patients with American Society of Anesthesiologists
      (ASA) I or II foot of cesarean section in full-term pregnant women for the first
      time production of Quanzhou Women's and Children's Hospital were recruited,
      authenticated by Hospital Ethics Committee, they were randomly divided into three
      groups (Random number table), dual-chamber in the LMA group (A group of 100
      cases), tracheal intubation group (B group of 100 cases) and spinal anesthesia
      group (C group of 100 cases). ECG, SpO2, MAP, heart rate, Narcotrend and Apgar
      scores were observed. RESULTS: Before and after the LMA group inserted laryngeal
      mask HR,MAP no significant change in the performance of Narcotrend value remained
      at the level of anesthesia, intubation before and after HR, MAP significantly
      increased performance of Narcotrend values significantly increased, both compared
      to the obvious statistical difference (P < 0.05). The ventilation indicators of
      two groups compared to no significant difference (P > 0.05). LMA group cover
      required intubation time was significantly shorter than the time required for
      intubation of endotracheal intubation group (P < 0.01). Three groups of patient
      administration to the fetus at all times is in 5-10 min.Three groups similar to
      the Apgar score was no significant difference (P > 0.05). CONCLUSION: The dual
      chamber laryngeal mask airway for caesarean section anesthesia, fetal Apgar
      scores, feasibility, and its operation is easy, safe and comfortable anesthesia,
      compared tracheal intubation has obvious superiority.

PMID- 24029573
TI  - [Intraoperative decisions and surgical efficacies of trigeminal neuralgia
      responsible vessels].
AB  - OBJECTIVE: To explore the types of primary trigeminal neuralgia (TN) responsible
      vessels and curative efficacies of microscopic vascular decompression (MVD).
      METHODS: A total of 162 primary TN patients underwent MVD from August 2004 to the
      present at our hospital.Their clinical data were collected and analyzed. There
      were 69 males and 93 females with an age range of 22-88 years. RESULTS: The most
      common responsible vessels were superior cerebellar artery (n = 65, 40.12%),
      anteroinferior cerebellar artery (n = 45, 27.78%), multiple vessels (n = 26,
      16.05%), posteroinferior cerebellar artery (n = 16, 9.88%), veins (n = 6, 3.70%)
      and vertebral artery (n = 4, 2.47%). And the pressure points were at the root of
      trigeminal nerve (n = 139, 85.80%), distal part (n = 16, 9.88%) and root and
      distal part (n = 7, 4.32%). Postoperatively pain disappeared in all patients
      (including one case on second surgery). Postoperative follow-ups were conducted
      for 132 cases.Two cases recurred over 8 years and the recurrence rate was 1.52%.
      CONCLUSION: MVD is preferred method for primary TN non-responsive to
      pharmacotherapy. Identification and treatment of responsible vessels remain a
      key. Venous and distal pressure points should be taken care.

PMID- 24029574
TI  - [Magnetic resonance staging accuracy for endometrial carcinoma based on different
      FIGO staging systems].
AB  - OBJECTIVE: To evaluate MR accuracy for staging endometrial carcinoma with
      different FIGO staging systems. METHODS: Between August 2006 and July 2010, 95
      women underwent surgery for endometrial carcinoma.In each patient, endometrial
      carcinoma was staged with magnetic resonance (MR) findings based on the old FIGO
      staging system and then repeated according to the new FIGO staging system for
      comparisons.Histopathologic findings were used as a golden standard to compare
      the sensitivity, specificity, accuracy, positive predictive value and negative
      predictive value. RESULTS: The accuracy of MRI in the staging of endometrial
      carcinoma stageI, II and III with the old FIGO staging system were 83.2%, 86.3%
      and 92.6% versus 88.4%, 96.8% and 91.6% respectively with the new FIGO staging
      criteria.According the old FIGO staging system, the sensitivity of stage IA, IB
      and IC were 51.8%, 76.5% and 50.0% and the specificity 85.3% , 55.7% and 95.4%
      respectively; the sensitivity of stage IIA and IIB were merely 12.5% and 20.0%
      and the specificity 97.7% and 100.0%.With the new FIGO staging criteria, the
      above indices were 97.1%, 55.6%, 57.7%, 95.3%, 40.0% and 100.0% respectively.
      CONCLUSION: With new FIGO staging system versus the old one, the accuracy of MR
      imaging in the preoperative staging of endometrial carcinoma increases.

PMID- 24029575
TI  - [The role of SHH pathway in PDGF-induced VSMC proliferation].
AB  - OBJECTIVE: To discuss the role of sonic hedgehog (SHH) pathway in PDGF-induced
      vascular smooth muscle cell proliferation. METHOD: Human vein VSMC were cultured
      in vitro. Laser confocal microscopy and Western blot were used to detect the
      expression of SHH pathway related proteins. The cell proliferation was evaluated
      by Ki-67 staining and BrdU incorporation after treatment by siRNA of Gli2 or shh
      pathway inhibitor cyclopamine. RESULTS: The results of laser confocal microscopy
      and Western blot showed that SHH pathway protein which including shh, Patched1
      and Gli2 were activated in the PDGF-induced VSMC proliferation.BrdU incorporation
      assay and Ki-67 staining showed that the cell proliferation which induced by PDGF
      was inhibited by Gli2-siRNA and cyclopamine which can both block SHH pathway.
      CONCLUSION: SHH pathway play an important role in PDGF-induced VSMC
      proliferation.

PMID- 24029576
TI  - [Osteogenetic capacity of cross-linked adjustable anti-tuberculosis drug
      sustained-release artificial composite].
AB  - OBJECTIVE: To explore the osteogenetic capacity of cross-linked adjustable anti
      tuberculosis drug sustained-release artificial composite (TPB/SA-RFP/PLA).
      METHODS: The model of femur bone defect was established in rabbits.TPB/SA-RFP/PLA
      complex was implanted into defect parts in the experimental group while
      TPB/SA/PLA in the blank control group. At Weeks 4, 8 and 12, gross specimens
      received radiographic, histological and immunohistochemical examinations to
      determine the osteogenetic performance of TPB/SA-RFP/PLA. RESULTS: As compared
      with the control group, TPB/SA-RFP/PLA complex had excellent osteogenic
      capacities while the TPB/SA/PLA group had no obvious osteogenic difference. Lane
      sandhu histological and radiographic ratings demonstrated significant difference
      between TPB/SA-RFP/PLA (8.3 +/- 0.3) and blank groups (2.2 +/- 0.4) (P < 0.05).
      And TPB/SA/PLA showed no significant intragroup significance (P > 0.05). Two
      groups immunohistochemical Alkaline phosphatase was strongly positive in two test
      groups and weakly positive in the control group. CONCLUSION: TPB/ SA-RFP/PLA has
      excellent profiles of bone conductivity and regeneration.And the incorporation of
      rifampin does not affect its osteogenetic capacity.

PMID- 24029577
TI  - [Inhibitory effects of human umbilical cord-derived mesenchymal stem cells on
      proliferation of peripheral blood mononuclear cells from spondyloarthritis
      patients].
AB  - OBJECTIVE: To explore the inhibitory effects of human umbilical cord-derived
      mesenchymal stem cells (hUCMSC) on the proliferation of peripheral blood
      mononuclear cells (PBMC) from spondyloarthritis (SpA) patients. METHODS: A total
      of 12 SpA patients at Chinese PLA General Hospital were recruited from May 2012
      to October 2012. Information on demographic characteristics, disease and
      functional activity was collected. Isolated PBMC were stimulated by
      phytohemagglutinin (PHA, 1 ug/ml) in the presence or absence of hUCMSC.The
      proliferation of hUCMSC was suppressed by irradiation with Co60 (30 Gy) before co
      culturing with PBMC. The proliferation of PBMC was determined by Cell Counting
      Kit-8 (CCK-8). Cell cycle profiles of PBMC were analyzed by flow cytometry. The
      association of inhibitory effect of hUCMSC with the disease and functional
      activity of SpA patients was examined. RESULTS: After coculturing with hUCMSC by
      cell-to-cell contact for 5 days, the proliferation of PBMC stimulated by PHA (1
      ug/ml) was significantly inhibited by hUCMSC in a dose-dependent manner.The
      inhibition rate of the proliferation of PBMC cocultured with hUCMSC by cell-to
      cell contact was higher than that by Transwell culture (57% +/- 17% vs 32% +/-
      12%, P < 0.01). Compared to PBMC cultured alone, a larger number of PBMC
      cocultured with hUCMSC were in phase G1 (86% +/- 3% vs 68% +/- 5%, P < 0.01)
      while a lower number of cells in phases S and G2 (8% +/- 3% vs 26% +/- 5%, P <
      0.01). No association was found between the inhibitory effect of hUCMSC and the
      disease and functional activity. CONCLUSION: The proliferation of PBMC from SpA
      patients may be inhibited by hUCMSC. And hUCMSC have therapeutic potentials for
      SpA patients.

PMID- 24029578
TI  - [Experimental study of tendon graft fixation in anterior cruciate ligament
      reconstruction with cortical press-fit bolt in rabbits].
AB  - OBJECTIVE: To explore the histological outcomes of tendon-bone healing in
      anterior cruciate ligament (ACL) reconstruction with cortical press-fit bolt
      (CPB). METHODS: Twenty-four healthy female or male New Zealand White rabbits (2-3
      months old) underwent bilateral ACL reconstruction with extensor digitorum longus
      tendon. A random method was used to decide one knee would receive the routine ACL
      reconstruction (control group) and another cortical press-fit bolt fixation
      (experimental group). After general anesthesia, extensor digitorum longus tendon
      was harvested and ACL reconstruction performed. All animals were sacrificed at 4,
      8 and 12 weeks postoperation. Radiological and histological examinations were
      made at each timepoint. The specimens were stained with different methods to
      observe the pathological changes of tendon graft, bone tunnel and cortical press
      fit bolt. RESULTS: More revascularization and massive new bone were found in
      tendon-bone junction of experimental group at 4, 8 and 12 weeks postoperation.
      The circum-graft new vessel proportion of the experimental and control groups
      were 0.48 +/- 0.12 and 0.26 +/- 0.05 respectively (P < 0.05). In the experimental
      group, more cartilage cells were present in tendon-bone junction at 12 weeks and
      the circum-graft new bone areas in two groups were 0.41 +/- 0.11 and 0.21 +/-
      0.10 mm(2) respectively (P < 0.05). CONCLUSION: Cortical press-fit blot may
      improve tendon-bone healing after ACL reconstruction in rabbits. The application
      prospects of this procedure are promising.

PMID- 24029579
TI  - [Expression of cation-chloride cotransporters KCC2 and NKCC1 in brainstem of para
      chlorophenylalanine-induced acute insomnia rats].
AB  - OBJECTIVE: To explore the possible roles of KCC2 and NKCC1 in the pathological
      mechanism of acute insomnia in rats. METHODS: A total of 18 Sprague-Dawley rats
      were randomly selected into model, interference and normal control groups.The
      expressions of KCC2 and NKCC1 in brainstem were detected by reverse transcription
      polymerase chain reaction (RT-PCR) and Western blot.The concentration of
      intracellular Cl(-) ([Cl(-)]i) in brainstem was detected by fluorescence probe
      MQAE with laser confocal microscopy. RESULTS: (1) Comparing with the control
      group, both KCC2 mRNA and protein expression were down-regulated in the model and
      interference groups (mRNA:0.196 +/- 0.021 vs 0.939 +/- 0.109, P < 0.05; 0.485 +/-
      0.026 vs 0.939 +/- 0.109, P < 0.05; protein expression:0.363 +/- 0.058 vs 0.967
      +/- 0.155, P < 0.05; 0.663 +/- 0.106 vs 0.967 +/- 0.155, P < 0.05).However they
      became up-regulated in the interference group versus the model group (mRNA: 0.485
      +/- 0.026 vs 0.196 +/- 0.021, P < 0.05; protein expression:0.663 +/- 0.106 vs
      0.363 +/- 0.058, P < 0.05). (2) Comparing with the control group, both NKCC1 mRNA
      and protein expression in the model group were slightly up-regulated.But
      statistical difference was insignificant (mRNA: 0.344 +/- 0.026 vs 0.320 +/-
      0.019, P > 0.05; protein expression:0.244 +/- 0.010 vs 0.230 +/- 0.021, P >
      0.05).There was down-regulation in the interference group versus the model and
      control groups (mRNA: 0.066 +/- 0.031 vs 0.320 +/- 0.019, P < 0.05; 0.066 +/-
      0.031 vs 0.344 +/- 0.026, P < 0.05; protein expression:0.131 +/- 0.012 vs 0.230
      +/- 0.021, P < 0.05; 0.131 +/- 0.012 vs 0.244 +/- 0.010, P < 0.05). (3) Comparing
      with the control group, [Cl(-)]i became up-regulated in the model group (0.0315
      +/- 0.0039 vs 0.0164 +/- 0.0019, P < 0.05).It was down-regulated in the
      interference group versus the model group (0.0182 +/- 0.0013 vs 0.0315 +/-
      0.0039, P < 0.05), but higher than control group without statistical difference
      (0.0182 +/- 0.0013 vs 0.0164 +/- 0.0019, P > 0.05). CONCLUSION: The down
      regulation of KCC2 and rise of [Cl(-)]i in brainstem may participate in the
      pathological mechanism of acute insomnia in rats. And the mechanism of sedative
      hypnotic diazepam may be operate through an up-regulation of KCC2, a down
      regulation of NKCC1 and decreased [Cl(-)]i.

PMID- 24029581
TI  - Using a 'talk' model of shared decision making to propose an observation-based
      measure: Observer OPTION 5 Item.
AB  - OBJECTIVE: To propose a revised Observer OPTION measure of shared decision
      making. METHODS: We analyzed published models to identify the core components of
      a parsimonious conceptual framework of shared decision making. By using this
      framework, we developed a revised measure combining data from an observational
      study of clinical practice in Canada with our experience of using Observer
      OPTION(12 Item). RESULTS: Our conceptual framework for shared decision making
      composed of justifying deliberative work, followed by the steps of describing
      options, information exchange, preference elicitation, and preference
      integration. By excluding items in Observer OPTION(12 Item) that were seldom
      observed or not aligned to a robust construct, we propose Observer OPTION(5
      Item). CONCLUSION: Although widely used, Observer OPTION(12 Item) did not give
      sufficient attention to preference elicitation and integration, and included
      items that were not specific to a core construct of shared decision making. We
      attempted to remedy these shortcomings by proposing a shorter, more focused
      measure. PRACTICE IMPLICATIONS: Observer OPTION(5 Item) requires evaluation; we
      hope that it will be useful as both a research tool and as a formative measure of
      clinical practice.

PMID- 24029580
TI  - Mimicry epitope from Ehrlichia canis for interphotoreceptor retinoid-binding
      protein 201-216 prevents autoimmune uveoretinitis by acting as altered peptide
      ligand.
AB  - We report here identification of novel mimicry epitopes for interphotoreceptor
      retinoid-binding protein (IRBP) 201-216, a candidate ocular antigen that causes
      experimental autoimmune uveoretinitis (EAU) in A/J mice. One mimicry epitope from
      Ehrlichia canis (EHC), designated EHC 44-59, induced cross-reactive T cells for
      IRBP 201-216 capable of producing T helper (Th)1 and Th17 cytokines, but failed
      to induce EAU in A/J mice. In addition, animals first primed with suboptimal
      doses of IRBP 201-216 and subsequently immunized with EHC 44-59 did not develop
      EAU; rather, the mimicry epitope prevented the disease induced by IRBP 201-216.
      However, alteration in the composition of EHC 44-59 by substituting alanine with
      valine at position 49, similar to the composition of IRBP 201-216, enabled the
      mimicry epitope to acquire uveitogenicity. The data provide new insights as to
      how microbes containing mimicry sequences for retinal antigens can prevent ocular
      inflammation by acting as naturally occurring altered peptide ligands. 

PMID- 24029582
TI  - Self-management support needs of patients with chronic illness: do needs for
      support differ according to the course of illness?
AB  - OBJECTIVE: To determine whether chronically ill patients' needs for self
      management support depend on their course of illness. METHODS: Cross-sectional
      and longitudinal linear regression analyses were conducted using data from 1300
      patients with chronic disease(s) who participated in a nationwide Dutch panel
      study. Self-management support needs were assessed by the Patient Assessment of
      Self-management Tasks questionnaire (PAST). Course of illness was operationalized
      as: illness duration, patients' perception of the course of illness and changes
      in self-rated general health (RAND-36). RESULTS: Self-management support needs
      are not related to illness duration. Patients who perceive their illness as
      episodic and/or progressively deteriorating have greater self-management support
      needs than patients who perceive their illness as stable. Deterioration of self
      rated health is related to increased support needs. The effect of the course of
      illness on support needs depends on the type of self-management activities.
      CONCLUSION: How chronically ill patients perceive the course of illness and
      actual changes in self-rated health are predictive for their need for support for
      self-management activities. Illness duration is not. PRACTICE IMPLICATIONS:
      Helping patients to self-manage should not be confined to the first years after
      diagnosis. Healthcare providers should be alert to patients' own perceptions of
      their course of illness and health status.

PMID- 24029583
TI  - Marvin: an anatomical phantom for dosimetric evaluation of complex radiotherapy
      of the head and neck.
AB  - We report on the design of Marvin, a Model Anatomy for Radiotherapy Verification
      and audit In the head and Neck and present results demonstrating its use in the
      development of the Elekta volumetric modulated arc therapy (VMAT) technique at
      the Christie, and in the audit of TomoTherapy and Varian RapidArc at other
      institutions. The geometry of Marvin was generated from CT datasets of eight male
      and female patients lying in the treatment position, with removable
      inhomogeneities modelling the sinuses and mandible. A modular system allows the
      phantom to be used with a range of detectors, with the locations of the modules
      being based on an analysis of a range of typical treatment plans (27 in total)
      which were mapped onto the phantom geometry. Results demonstrate the use of
      Gafchromic EBT2/EBT3 film for measurement of relative dose in a plane through the
      target and organs-at-risk, and the use of a small-volume ionization chamber for
      measurement of absolute dose in the target and spinal cord. Measurements made
      during the development of the head and neck VMAT protocol at the Christie
      quantified the improvement in plan delivery resulting from the installation of
      the Elekta Integrity upgrade (which permits an effectively continuously variable
      dose rate), with plans delivered before and after the upgrade having 88.5 +/-
      9.4% and 98.0 +/- 2.2% respectively of points passing a gamma analysis (at 4%, 4
      mm, global). Audits of TomoTherapy and Varian RapidArc neck techniques at other
      institutions showed a similar quality of plan delivery as for post-Integrity
      Elekta VMAT: film measurements for both techniques had >99% of points passing a
      gamma analysis at the clinical criteria of 4%, 4 mm, global, and >95% of points
      passing at tighter criteria of 3%, 3 mm, global; and absolute dose measurements
      in the PTV and spinal cord were within 1.5% and 3.5% of the planned doses
      respectively for both techniques. The results demonstrate that Marvin is an
      efficient and effective means of assessing the quality of delivery of complex
      radiotherapy in the head and neck, and is a useful tool to assist development and
      audit of these techniques. 

PMID- 24029584
TI  - Correction of malformative patellar instability in patients with nail-patella
      syndrome: a case report and review of the literature.
AB  - Nail-patella syndrome (NPS) or hereditary onycho-osteodysplasia is a relatively
      rare autosomal dominant disorder with the classic tetrad of fingernail
      abnormalities, hypoplastic patellae, radial head dislocation and iliac horns. The
      anatomic abnormalities in NPS often lead to subluxation or dislocation of the
      patellaeca causing knee instability and pain. Although most existing literature
      regarding the knee manifestation of this syndrome has focused on the clinically
      and radiological changes, only a few articles discussed the surgical treatment.
      This study reports the clinical, radiological and arthroscopical findings and a
      24-month follow-up after operative stabilisation considering the underlying
      pathomorphology of malformative patellar instability in an 11-year-old girl. The
      findings of this study confirm the unique pathology of NPS with a synovial band
      preventing the engagement of the patella into the trochlear groove. NPS is a rare
      disorder and has to be considered in cases with untypical patella dislocation.
      The underlying pathology differs completely from patients with patellofemoral
      instability. The aim of orthopaedic surgery should be correction of the
      underlying pathology with resection of the synovial band and an additional
      realignment of the patella by recentering of the quadriceps muscle. Considering
      the underlying pathology good clinical results can be expected. 

PMID- 24029585
TI  - Fractures of the distal humerus operated on using the Lambda(r) plate: report of
      75 cases at 9.5 years follow-up.
AB  - INTRODUCTION: The study sought to assess the functional results and complications
      of osteosynthesis using the Lambda((r)) plate (Zimmer, Etupes, France) in
      treating fracture of the distal extremity of the humerus. MATERIALS AND METHODS:
      The initial series comprised 115 patients (116 fractures), treated between 1992
      and 2008. Forty-one (mainly foreigners) were lost to follow-up. The final series
      thus comprised 74 patients (75 fractures): 44 female and 30 male, with a mean age
      of 46+/-23 years (range, 16-95 years), 22 (29%) being aged 65 years or over.
      According to AO classification, 22 of the fractures of the distal extremity of
      the humerus (29%) were diaphyseal-metaphyseal, corresponding to a particular
      grade of type A2, 12 (16%) were type A2 or A3, six (8%) type B, and 35 (47%) type
      C. Eight were open fractures: seven grade 1 and one grade IIa on Gustilo's
      classification. The Lambda((r)) plate is an inverted Y shape, with a stem of up
      to ten holes and sectile arms that can be remodeled to adapt perfectly to the
      type of fracture and the shape of the distal end of the humerus. A posterior
      approach was used in all cases: in 26 cases, an extra-articular transolecranal
      approach and otherwise a transtricipital approach, either vertical for diaphyseal
      metaphyseal fracture or inverted V for type-C fracture. RESULTS: Mean follow-up
      was 115+/-64 months (range, 24-227 months). There were no cases of infection, non
      union of olecranial osteotomy or disassembly of the internal fixation; there was,
      on the other hand, one case of non-union of the lateral condyle and one of the
      distal extremity of the humerus, two cases of dysesthesia in the ulnar nerve
      territory and one in the radial nerve territory (following preoperative
      paralysis), and four cases of stiffness requiring surgical arthrolysis between 6
      and 12 months postoperatively. At follow-up, mean active elbow flexion was 133
      degrees +/-13 degrees  (range, 90 degrees -150 degrees ) and active extension -12
      degrees +/-14 degrees  (range, -45 degrees -0 degrees ). Mean elbow flexion range
      of motion exceeded 100 degrees  in 58 patients (77%), was between 50 degrees  and
      100 degrees  in 16 (21%) and was less than 50 degrees  in one. Mean Mayo Elbow
      Performance Score (MEPS) was 97+/-7 points (range, 40-100), and mean Quick DASH
      Score (converted as a score out of 100) was 10+/-18 (range, 0-54). There were 67
      excellent results (MEPS, 90-100 points), five good (75-89), two moderate and one
      poor. The 35 type-C fractures displayed no significant differences from the
      series as a whole (P=1.24 for MEPS). CONCLUSION: Osteosynthesis using the
      Lambda((r)) plate gave excellent medium-term results in terms of both fixation
      stability and recovery of elbow function after fracture of the distal extremity
      of the humerus, even in elderly osteoporotic patients. LEVEL OF EVIDENCE: Level
      IV: retrospective study.

PMID- 24029586
TI  - Primary-care physicians' patient referral patterns to private versus public
      hospitals for orthopaedic or trauma surgery-- French Sentinels(r) database, 1997
      2011.
AB  - BACKGROUND: In France, primary-care physicians referring patients for admission
      can choose between public and private hospitals. The factors that govern their
      choices are unknown. METHODS: Among all patient admissions reported from 1997 to
      2011 by primary-care physicians participating in the Sentinels((r)) network, we
      identified those due to orthopaedic conditions or trauma. We then identified the
      factors associated with referral to a private hospital rather than to a public
      hospital. RESULTS: Of 45,960 admissions reported to Sentinels((r)) in 1997-2011,
      2794 (6.1%) were for orthopaedic/trauma care. The main reasons for admission were
      hip fractures (27.5%), elective orthopaedic surgery (15.5%), fractures of the
      humerus (5.9%), wrist fractures (5.4%), soft-tissue lesions of the forearm or
      hand (5.0%), and spinal injuries (4.5%). Private hospitals were chosen more often
      for orthopaedic/trauma patients than for patients with other conditions (40% vs.
      21.6% of cases, P<0.0001). When fracture of the humerus was used as the
      reference, referral to private hospitals was significantly more common for
      elective surgery (odds ratio, 3.30 [2.02-5.40]) and hip fracture (odds ratio,
      1.50 [1.03-2.18]) and significantly less common for spinal injuries (odds ratio,
      0.35 [0.19-0.66]). Other factors associated with referral to private hospitals
      were patient age, admission decision during an office visit or in a non-emergent
      setting, and admission decision made by the patient's usual physician.
      CONCLUSION: Specific factors seem to govern decisions by primary-care physicians
      to refer orthopaedic/trauma patients to private vs. public hospitals. Identical
      pricing scales for private and public hospitals will be implemented soon in
      France, a change that requires further analyses. LEVEL OF EVIDENCE: Level IV.

PMID- 24029587
TI  - Can physics help to explain embryonic development? An overview.
AB  - Recent technical advances including digital imaging and particle image
      velocimetry can be used to extract the full range of embryonic movements that
      constitute the instantaneous 'morphogenetic fields' of a developing animal. The
      final shape of the animal results from the sum over time (integral) of the
      movements that make up the velocity fields of all the tissue constituents. In
      vivo microscopy can be used to capture the details of vertebrate development at
      the earliest embryonic stages. The movements thus observed can be quantitatively
      compared to physical models that provide velocity fields based on simple
      hypotheses about the nature of living matter (a visco-elastic gel). This approach
      has cast new light on the interpretation of embryonic movement, folding, and
      organisation. It has established that several major discontinuities in
      development are simple physical changes in boundary conditions. In other words,
      with no change in biology, the physical consequences of collisions between folds
      largely explain the morphogenesis of the major structures (such as the head).
      Other discontinuities result from changes in physical conditions, such as
      bifurcations (changes in physical behaviour beyond specific yield points). For
      instance, beyond a certain level of stress, a tissue folds, without any new gene
      being involved. An understanding of the physical features of movement provides
      insights into the levers that drive evolution; the origin of animals is seen more
      clearly when viewed under the light of the fundamental physical laws (Newton's
      principle, action-reaction law, changes in symmetry breaking scale). This article
      describes the genesis of a vertebrate embryo from the shapeless stage (round mass
      of tissue) to the development of a small, elongated, bilaterally symmetric
      structure containing vertebral precursors, hip and shoulder enlarges, and a head.

PMID- 24029588
TI  - Skin preparation before hip replacement in emergency setting versus elective
      scheduled arthroplasty: bacteriological comparative analysis.
AB  - INTRODUCTION: Hip arthroplasty needs to be performed in an emergency setting
      after intracapsular femur neck fracture, whereas pain makes preoperative skin
      preparation of the limb difficult and it may therefore be incomplete. To date no
      study has analyzed the patient's skin bacteriological status in these surgical
      conditions. HYPOTHESIS: The skin's bacterial flora is quantitatively and
      qualitatively different in the trauma context compared to an elective scheduled
      arthroplasty for chronic hip disease. MATERIALS AND METHODS: Two groups of
      patients, undergoing hip arthroplasty and having the same preparation at the time
      of surgery but different skin preparation procedures the day before and the day
      of surgery, were prospectively compared: 30 patients operated on in an emergency
      setting for fracture (group A) had no skin preparation and 32 patients operated
      on in scheduled surgery (group B). Group A had no skin disinfection before going
      into surgery, whereas group B followed a predefined protocol the day before
      surgery. Skin samples were taken on gelose at three different stages of skin
      preparation at the time of surgery (before and after detersive cleaning, and at
      the end of the surgery) and on two sites (inguinal and greater trochanter). The
      bacteriological analysis took place after 48 hours of incubation. RESULTS: Before
      detersive cleaning, group A had 3.6 times more bacteria than group B in the
      trochanter region and 2.7 times more in the inguinal area. After detersive
      cleaning, the contamination rate in the trochanter area was similar in both
      groups (group A: 10%; group B: 12.5%), but different in the inguinal region
      (group A: 33%; group B: 3%; P=0.002). At the end of the surgery, no difference
      was identified. Coagulase-negative Staphylococcus and Bacillus cereus accounted
      for 44% and 37%, respectively, of the bacteria isolated. In addition, the
      frequency of pathogenic non-saprotrophic bacteria was higher in group A (38%)
      compared to group B (6%). At a mean follow-up of 9.7 months (range: 8-11 months),
      no infection of the surgical site was identified. CONCLUSION: The dermal flora is
      more abundant and different when the patient is managed in an emergency context.
      Although effective in the trochanter area, cutaneous detersive cleaning in the
      operating room is insufficient in the inguinal area and the frequency of
      pathogenic bacteria warrants identical rigor in preoperative preparation in all
      situations. LEVEL OF EVIDENCE: III. Prospective case - control study.

PMID- 24029590
TI  - Microvascular architecture of mouse urinary bladder described with vascular
      corrosion casting, light microscopy, SEM, and TEM.
AB  - The urinary bladder is a unique organ in that its normal function is storage and
      release of urine, and vasculature in its wall exhibits specialized features
      designed to accommodate changes in pressure with emptying and filling. Although
      we have previously described the fine details of the microvasculature of the
      urinary bladder of the rabbit and dog, information on the fine details of the
      microvasculature of the mouse bladder were deemed to be of value because of the
      increasing use of this species in developing genetic models for studying human
      disorders. The present study shows that many of the special features of the
      microvasculature of the mouse urinary bladder are similar to those described in
      the rabbit and dog, including vessel coiling, abundant collateral circulation,
      arterial sphincters, and a dense mucosal capillary plexus. 

PMID- 24029591
TI  - Lymphangiogenesis and lymphatic function in periodontal disease.
AB  - Lymphatic vessels return extravasated fluid, proteins, and cells back into the
      circulation and are important in immune cell trafficking. In the gingiva,
      lymphatic vessels are located in the lamina propria and travel over the external
      surface of the alveolar bone. The gingival lymphatics are important for fluid
      drainage, since lack of lymphatics has been shown to increase interstitial fluid
      pressure and fluid volume. Maintenance of gingival lymphatic vessels requires
      continuous signaling by the growth factors VEGF-C and -D via their receptor VEGFR
      3. The growth factors are expressed in the gingival epithelium and also in immune
      cells in the lamina propria. VEGF-C seems to be crucial for lymphangiogenesis
      induced during periodontal disease development. The lymphatic vessels protect
      against periodontitis in mice, probably by clearing bacteria and bacterial
      products and by promoting humoral immune responses. Down-regulation of CCL21, a
      ligand important for dendritic cell migration, has been demonstrated in
      lymphatics from patients with periodontitis. High enzymatic activity in the
      gingiva of these patients may also contribute to impaired lymphatic function, due
      to the loss of structural components in the interstitium influencing lymphatic
      function. So far, knowledge is limited in this field because of the dearth of
      studies on the role of lymphatic vessels in periodontal disease.

PMID- 24029592
TI  - The gap between trial data and clinical practice -- an analysis of case reports
      on bleeding complications occurring under dabigatran and rivaroxaban
      anticoagulation.
AB  - BACKGROUND: The novel direct oral anticoagulants (NOA), dabigatran (a thrombin
      inhibitor), rivaroxaban and apixaban (factor Xa inhibitors) have shown at least
      noninferiority compared to warfarin concerning the prevention of stroke and
      systemic embolism as well as the risk of hemorrhagic complications in large phase
      III trials in patients with atrial fibrillation (AF). These results have been
      obtained under regular monitoring of side effects and reinforcement of medication
      adherence in carefully controlled clinical trials. To what extent they translate
      into clinical practice is a matter of ongoing research. While postmarketing
      registers, most prominently the GLORIA-AF registry, are currently recruiting and
      will not report data for several years, we aimed at extracting risk factors for
      hemorrhagic complications under NOA from all available case reports and single
      case series published to date. METHODS: To identify risk factors which increase
      the risk of hemorrhage under NOA, we performed a PubMed search for both
      dabigatran and rivaroxaban, as well as three search terms for hemorrhagic
      complications. The cases of hemorrhagic complications were analyzed for the
      presence of the following four factors: 'prescriber errors', 'unfavorable
      comedications', 'renal impairment' and 'prescription of NOA in the frail
      elderly'. RESULTS AND DISCUSSION: We found a discrepancy in the frequency of case
      reports on hemorrhagic complications to the disadvantage of dabigatran which can
      hardly be attributed to the earlier marketing time of dabigatran alone. As risk
      factors, we identified prescriber errors, impaired renal function, comedication
      with antiplatelet drugs or p-glycoprotein inhibitors, old age and low body
      weight. Strikingly, the majority of the bleeding complications reported in this
      compilation of case reports showed at least one and in most cases several risk
      factors. CONCLUSIONS: We should, therefore, carefully select our patients for
      treatment with the NOA with an emphasis on age, body weight, renal function and
      comedications and follow them faithfully concerning their medication adherence
      and eventual side effects.

PMID- 24029589
TI  - The E1 proteins.
AB  - E1, an ATP-dependent DNA helicase, is the only enzyme encoded by papillomaviruses
      (PVs). It is essential for replication and amplification of the viral episome in
      the nucleus of infected cells. To do so, E1 assembles into a double-hexamer at
      the viral origin, unwinds DNA at the origin and ahead of the replication fork and
      interacts with cellular DNA replication factors. Biochemical and structural
      studies have revealed the assembly pathway of E1 at the origin and how the enzyme
      unwinds DNA using a spiral escalator mechanism. E1 is tightly regulated in vivo,
      in particular by post-translational modifications that restrict its accumulation
      in the nucleus. Here we review how different functional domains of E1 orchestrate
      viral DNA replication, with an emphasis on their interactions with substrate DNA,
      host DNA replication factors and modifying enzymes. These studies have made E1
      one of the best characterized helicases and provided unique insights on how PVs
      usurp different host-cell machineries to replicate and amplify their genome in a
      tightly controlled manner. 

PMID- 24029593
TI  - A tetrahydroisoquinoline alkaloid THI-28 reduces LPS-induced HMGB1 and diminishes
      organ injury in septic mice through p38 and PI3K/Nrf2/HO-1 signals.
AB  - We investigated whether THI-28 [1-4-(hydroxyphenylethyl)-6,7-dihydroxy-1,2,3,4
      tetrahydroisoquinoline] inhibits release of high mobility group box 1 (HMGB1), a
      late phase cytokine of sepsis, in lipopolysaccharide (LPS)-stimulated RAW264.7
      cells through heme oxygenase (HO)-1 induction so that it shows beneficial effects
      in the cecal ligation and puncture (CLP)-induced septic mouse model. Silencing of
      target genes (HO-1, Nrf-2) or pharmacological signal inhibitors was exploited to
      investigate the HO-1 induction by THI-28. The dependency of HO-1 by THI-28 on
      survival rate and circulating HMGB1 level was tested in CLP-induced septic mice.
      Results showed that a time- and concentration-dependent HO-1 induction by THI-28
      was significantly reduced by transfection with siNrf2 RNA. The reduction of
      iNOS/NO and HMGB1 expression by THI-28 was significantly reversed by silencing HO
      1 RNA or treatment with SB203580, a p38 MAPK inhibitor, or LY294002, a PI3K
      inhibitor in LPS-activated cells. Decreasing p-IkappaBalpha by THI-28 resulted in
      inhibition of NF-kappaB activity which was reversed by silencing HO-1 RNA in LPS
      activated cells. Most importantly, increased survival and reduction of liver and
      kidney injury and circulating HMGB1 levels by THI-28 in CLP-mice were reversed by
      ZnPPIX, HO-1 inhibitor. Taken together, these findings suggest that the novel
      compound THI-28 induces the expression of HO-1 by activating the PI3K and p38
      MAPK pathways and suppressed HMGB1 and iNOS production in LPS-treated macrophages
      and septic mice, which may be useful in treating organ injury due to sepsis. 

PMID- 24029594
TI  - Poly(I:C) exhibits an anti-cancer effect in human gastric adenocarcinoma cells
      which is dependent on RLRs.
AB  - Poly(I:C), an agonist of TLR3 and RLRs, has been used as an immune adjuvant in
      clinical trials for many years. Although it has been found to trigger apoptosis
      in a variety of cancers, its mechanisms in human gastric adenocarcinoma is
      unclear. The purpose of this study was to assess the effect of poly(I:C) on human
      gastric adenocarcinoma cells. Our observations showed that intracellular delivery
      of poly(I:C) by liposomes had a pro-apoptotic effect in vitro, and significantly
      inhibited xenograft growth of human gastric adenocarcinoma in nude mice. Further
      investigations indicated that RLRs, as intrinsic RNA sensors, contributed to the
      poly(I:C)-triggered apoptotic effect through upregulation of RIG-I, MDA-5, and
      most significantly, LGP2, accompanied by increased expression of Bcl-2 family
      members. Conversely, this apoptotic effect was greatly reduced by silencing RIG
      I, MDA-5, or LGP2. Although LGP2 is considered an innate immune negative
      regulator of RIG-I and MDA-5, it exhibited a positive regulatory effect on
      poly(I:C)-induced apoptosis in human gastric adenocarcinoma cells. These findings
      suggested that poly(I:C) may be a promising chemotherapeutic agent against human
      gastric adenocarcinoma. 

PMID- 24029595
TI  - The tryptophan metabolite 3-hydroxyanthranilic acid suppresses T cell responses
      by inhibiting dendritic cell activation.
AB  - The generation of tryptophan (Trp) metabolites by indoleamine 2,3-dioxygenase
      (IDO) is an effective mechanism for T cell suppression. However, the effect of
      Trp metabolites on dendritic cells (DCs) remains unclear. Here, we investigated
      whether the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) directly
      inhibits DC activation and is responsible for T cell suppression. We found that 3
      HAA treatment significantly reduced IL-12, IL-6, and TNF-alpha production in bone
      marrow-derived DCs (BMDCs) stimulated with LPS. Maturation markers CD40, CD80,
      CD86, and I-A were also significantly reduced. Moreover, treatment with 3-HAA
      decreased the ability of DCs to stimulate T cell activation and differentiation
      in vitro and in vivo. Finally, we observed that phospho-JNK and phospho-38 levels
      were reduced in 3-HAA-treated DC2.4 cells and BMDCs. These results suggest that
      the tryptophan metabolite 3-HAA suppresses T cell responses by inhibiting DC
      activation. 

PMID- 24029596
TI  - Pain and bleeding pattern related to levonorgestrel intrauterine system (LNG-IUS)
      insertion.
AB  - OBJECTIVE: To investigate whether the pattern or pain or bleeding during
      levonorgestrel intrauterine system (LNG-IUS) insertion and in the first 6 weeks
      thereafter is altered by LNG-IUS malposition. STUDY DESIGN: Prospective cohort of
      413 women undergoing LNG-IUS insertion or replacement. A first questionnaire on
      pain perception was completed by the women immediately after insertion. In a
      second questionnaire the women were asked to record pain in the 3 days following
      insertion and both pain and bleeding from 4 to 6 weeks after insertion. Six weeks
      after insertion a 2D- and 3D-ultrasound examination was performed to evaluate the
      position of the LNG-IUS and of the uterus. RESULTS: Parity was inversely related
      to pain at insertion, in the first 3 days and at 4-6 weeks. LNG-IUS insertion was
      less painful in the postpartum period. Women who had had a LNG-IUS as prior
      contraceptive method reported a higher percentage of amenorrhea at 4-6 weeks. The
      position of the LNG-IUS or of the uterus did not influence the pain scores or the
      bleeding pattern. The fact that the LNG-IUS arms appeared embedded in the uterine
      wall on coronal 3D-volume reconstruction did not influence pain or the bleeding
      pattern. CONCLUSIONS: Because neither pain nor bleeding is a reliable predictor
      of LNG-IUS position, we suggest an ultrasound examination to confirm correct LNG
      IUS placement in all patients at about 6 weeks after insertion.

PMID- 24029597
TI  - Highly specific separation for antitumor Spiropreussione A from endophytic fungal
      [Preussia sp.] fermentation broth by one-step macroporous resins AB-8 treatment.
AB  - It is attractive to pharmaceutical works to seek useful material from endophytic
      fungi. Spiropreussione A (SA) which is isolated from endophytic fungus Preussia
      sp. is a novel anti-tumor product. Since previous preparation method cannot
      provide enough SA, and considering the large volume of broth and low
      concentration of the target product, macroporous resins were introduced to
      separate SA in our study. Four kinds of macroporous resins ADS-8, H103, X-5 and
      AB-8 were applied for separating SA, and AB-8 was selected as the optimal resin
      according to its performances through static and dynamic measurements. HPLC was
      used to analyze SA in all samples. Under optimal conditions, the specific SA
      adsorption capacity of AB-8 resin was 15.23mg/g, and the purity increased by 2.5
      fold from 35.0% in broth to 90.0% in eluent with 70.0% recovery yield by a one
      step treatment. Conclusively, our study achieved the goal of separating and
      purifying SA in high efficiency, and offered references for further fermentation
      works. 

PMID- 24029598
TI  - Automating annotation of information-giving for analysis of clinical
      conversation.
AB  - OBJECTIVE: Coding of clinical communication for fine-grained features such as
      speech acts has produced a substantial literature. However, annotation by humans
      is laborious and expensive, limiting application of these methods. We aimed to
      show that through machine learning, computers could code certain categories of
      speech acts with sufficient reliability to make useful distinctions among
      clinical encounters. MATERIALS AND METHODS: The data were transcripts of 415
      routine outpatient visits of HIV patients which had previously been coded for
      speech acts using the Generalized Medical Interaction Analysis System (GMIAS); 50
      had also been coded for larger scale features using the Comprehensive Analysis of
      the Structure of Encounters System (CASES). We aggregated selected speech acts
      into information-giving and requesting, then trained the machine to automatically
      annotate using logistic regression classification. We evaluated reliability by
      per-speech act accuracy. We used multiple regression to predict patient reports
      of communication quality from post-visit surveys using the patient and provider
      information-giving to information-requesting ratio (briefly, information-giving
      ratio) and patient gender. RESULTS: Automated coding produces moderate
      reliability with human coding (accuracy 71.2%, kappa=0.57), with high correlation
      between machine and human prediction of the information-giving ratio (r=0.96).
      The regression significantly predicted four of five patient-reported measures of
      communication quality (r=0.263-0.344). DISCUSSION: The information-giving ratio
      is a useful and intuitive measure for predicting patient perception of provider
      patient communication quality. These predictions can be made with automated
      annotation, which is a practical option for studying large collections of
      clinical encounters with objectivity, consistency, and low cost, providing
      greater opportunity for training and reflection for care providers.

PMID- 24029600
TI  - Cerebrospinal fluid tau levels predict prognosis in non-inherited frontotemporal
      dementia.
AB  - BACKGROUND: The course of frontotemporal dementia (FTD) is heterogeneous and no
      predictors of survival are currently available. Cerebrospinal fluid (CSF) tau
      dosage has been demonstrated to be useful in predicting outcome over time in a
      number of neurological disorders. OBJECTIVE: To assess CSF tau levels in FTD and
      to evaluate their prognostic value. METHODS: Seventy-seven FTD patients with no
      mutations in known causative genes were consecutively enrolled, and CSF tau and
      phospho-tau levels analysed. Each patient was reassessed over time, and survival
      (i.e. death/bedridden and otherwise) was evaluated. The survival analysis was
      carried out by Cox proportional hazards regression models. RESULTS: Patients with
      high CSF tau levels (>=400 pg/ml) had shorter survival than those with low CSF
      tau levels [hazard ratio (HR) = 3.406; 95% CI: 1.151-10.077; Wald chi(2) = 4.902;
      d.f. = 1; p = 0.027]. The association between tau levels and survival probability
      was confirmed after adjusting for age, gender, clinical phenotype and FTD
      clinical dementia rating at enrolment (HR = 3.769; 95% CI: 1.143-12.433; Wald
      chi(2) = 4.748; d.f. = 1; p = 0.029). Neither demographic or clinical
      characteristics nor CSF phospho-tau levels or apolipoprotein E genotype were
      significantly associated with prognosis. CONCLUSIONS: This study argues that CSF
      tau levels may be considered in FTD to predict patients' outcome. Establishing in
      vivo prognostic biomarkers is mandatory to define homogeneous groups for
      inclusion in future clinical trials and to monitor the effectiveness of future
      therapeutic approaches.

PMID- 24029599
TI  - Use of IndiGO individualized clinical guidelines in primary care.
AB  - OBJECTIVE: To determine if IndiGO individualized clinical guidelines could be
      implemented in routine practice and assess their effects on care and care
      experience. METHODS: Matched comparison observational design. IndiGO
      individualized guidelines, based on a biomathematical simulation model, were used
      in shared decision-making. Physicians and patients viewed risk estimates and
      tailored recommendations in a dynamic user interface and discussed them for 5-10
      min. Outcome measures were prescribing and dispensing of IndiGO-recommended
      medications, changes in physiological markers and predicted 5-year risk of heart
      attack and stroke, and physician and patient perceptions. RESULTS: 489 patients
      using IndiGO were 4.9 times more likely to receive a statin prescription than
      were matched usual care controls (p=0.015). No effect was observed on prescribing
      of antihypertensive medications, but IndiGO-using patients were more likely to
      pick up at least one dispensing (p<0.05). No significant changes were observed in
      blood pressure or serum lipid levels. Predicted risk of heart attack or stroke
      decreased 1.6% among patients using IndiGO versus 1.0% among matched controls
      (p<0.01). Physician and patient experiences were positive to neutral.
      LIMITATIONS: We could not assess the separate effects of individualized
      guidelines, user interface, and physician-patient discussions. Patient selection
      could have influenced results. The measure of risk reduction was not independent
      of the individualized guidelines. CONCLUSIONS: IndiGO individualized clinical
      guidelines were successfully implemented in primary care and were associated with
      increases in the use of cardioprotective medications and reduction in the
      predicted risk of adverse events, suggesting that a larger trial could be
      warranted.

PMID- 24029602
TI  - Targeting the PD1/PD-L1 axis in melanoma: biological rationale, clinical
      challenges and opportunities.
AB  - A dynamic interplay exists between host and tumor, and the ability of the tumor
      to evade immune recognition often determines the clinical course of the disease.
      Significant enthusiasm currently exists for a new immunotherapeutic strategy: the
      use of immunomodulatory monoclonal antibodies that directly enhance the function
      of components of the anti-tumor immune response such as T cells, or block
      immunologic checkpoints that would otherwise restrain effective anti-tumor
      immunity. This strategy is based on the evidence that development of cancer is
      facilitated by the dis-regulation and exploitation of otherwise physiological
      pathways that, under normal circumstances, down-regulate immune activation and
      maintain tolerance to self. Among these pathways an important role is covered by
      the Programmed death-1 (PD-1)/PD-Ligand (L) 1 axis. An emerging concept in cancer
      immunology is that inhibitory ligands such as PD-L1 are induced in response to
      immune attack, a mechanism termed "adaptive resistance". This potential mechanism
      of immune resistance by tumors suggests that therapy directed at blocking the
      interaction between PD-1 and PD-L1 might synergize with other treatments that
      enhance endogenous antitumor immunity. The anti-PD-1 strategy can be effective in
      several solid tumors such as renal cell carcinoma (RCC) or non-small cell lung
      cancer (NSCLC), however in this review we summarize the biological role of PD
      1/PD-L1 on cancer by focusing our attention in the biological rationale, clinical
      challenges and opportunities to target the PD-1/PD-L1 axis in melanoma.

PMID- 24029601
TI  - The association of parity with osteoarthritis and knee replacement in the
      multicenter osteoarthritis study.
AB  - OBJECTIVE: We evaluated the association of parity to both risk of knee
      replacement (KR) and knee osteoarthritis (OA). DESIGN: The NIH-funded Multicenter
      Osteoarthritis Study (MOST) is a longitudinal observational study of persons age
      50-79 years with either symptomatic knee OA or at elevated risk of disease.
      Baseline and 30-month knee radiographic OA (ROA) was defined as Kellgren/Lawrence
      (K/L) grade >=2 or KR. Women were grouped based by number of births: 0; 1
      (reference group); 2; 3; 4; and 5 or more. We examined the relation of parity to
      the incidence over 30 months of ROA and KR using a Poisson regression model.
      Generalized estimating equations (GEE) were used to control for correlation
      between two knees within a subject. We adjusted for age, BMI, race, education,
      occupation, baseline estrogen use, clinical site, injury, and for KR analyses
      WOMAC pain and use of pain medication. RESULTS: Among 1618 women who reported
      parity information, mean age was 62.6 years, mean BMI 30.7 kg/m(2), mean WOMAC
      pain subscale score 3.7 at baseline. There were 115 KRs and 134 cases of incident
      knee ROA over 30 months. The relative risk of incident KR was 2.7 times as high
      (95% CI: 1.0, 7.3) and relative risk of incident knee ROA was 2.6 times as high
      (95% CI: 1.2, 5.3) among women with five to 12 children compared with those with
      one birth. CONCLUSION: Parity in women at risk for OA is associated with both
      incident ROA and KR, particularly for those with more than four children.

PMID- 24029603
TI  - Biomarkers in bladder cancer: translational and clinical implications.
AB  - Bladder cancer is associated with high recurrence and mortality rates. These
      tumors show vast heterogeneity reflected by diverse morphologic manifestations
      and various molecular alterations associated with these disease phenotypes.
      Biomarkers that prospectively evaluate disease aggressiveness, progression risk,
      probability of recurrence and overall prognosis would improve patient care.
      Integration of molecular markers with conventional pathologic staging of bladder
      cancers may refine clinical decision making for the selection of adjuvant and
      salvage therapy. In the past decade, numerous bladder cancer biomarkers have been
      identified, including various tumor suppressor genes, oncogenes, growth factors,
      growth factor receptors, hormone receptors, proliferation and apoptosis markers,
      cell adhesion molecules, stromal factors, and oncoproteins. Recognition of two
      distinct pathways for urothelial carcinogenesis represents a major advance in the
      understanding and management of this disease. Nomograms for combining results
      from multiple biomarkers have been proposed to increase the accuracy of clinical
      predictions. The scope of this review is to summarize the major biomarker
      findings that may have translational and clinical implications.

PMID- 24029604
TI  - Oxaliplatin induced-neuropathy in digestive tumors.
AB  - Oxaliplatin is one of the main drugs used in digestive tumors treatment.
      Peripheral neuropathy is a well-recognized dose-limiting toxicity of OXL. Two
      types of neuropathy have been described with this agent: acute or transient and
      chronic or persistent, with different etiology, clinical manifestations and
      prognosis. This paper is an exhaustive review about the main aspects of
      oxaliplatin induced peripheral neuropathy, focus in clinical features, treatment,
      prevention strategies and future approach.

PMID- 24029606
TI  - High field breakdown characteristics of carbon nanotube thin film transistors.
AB  - The high field properties of carbon nanotube (CNT) network thin film transistors
      (CN-TFTs) are important for their practical operation, and for understanding
      their reliability. Using a combination of experimental and computational
      techniques we show how the channel geometry (length L(C) and width W(C)) and
      network morphology (average CNT length L(t) and alignment angle distribution
      theta) affect heat dissipation and high field breakdown in such devices. The
      results suggest that when WC >= L(t), the breakdown voltage remains independent
      of W(C) but varies linearly with L(C). The breakdown power varies almost linearly
      with both W(C) and L(C) when WC >> L(t). We also find that the breakdown power is
      more susceptible to the variability in the network morphology compared to the
      breakdown voltage. The analysis offers new insight into the tunable heat
      dissipation and thermal reliability of CN-TFTs, which can be significantly
      improved through optimization of the network morphology and device geometry.

PMID- 24029605
TI  - Interleukin-6: an angiogenic target in solid tumours.
AB  - During the past decade, incorporating anti-angiogenic agents into the therapeutic
      management of a myriad of malignancies has in certain cases made a significant
      impact on survival. However, the development of resistance to these drugs is
      inevitable and swift disease progression on their cessation often ensues. Hence,
      there is a drive to devise strategies that aim to enhance response to anti
      angiogenic therapies by combining them with other targeted agents that facilitate
      evasion from resistance. The pleiotropic cytokine, interleukin-6 (IL-6), exerts
      pro-angiogenic effects in the tumour microenvironment of several solid
      malignancies and there is emerging evidence that reveals significant
      relationships between IL-6 signalling and treatment failure with antibodies
      directed against vascular endothelial growth factor (VEGF). This review
      summarises the role of IL-6 in pivotal angiogenic processes and
      preclinical/clinical research to support the future introduction of anti-IL-6
      therapies to be utilised either in combination with other anti-angiogenic drugs
      or as a salvage therapy for patients with diseases that become refractory to
      these approaches.

PMID- 24029607
TI  - Prosthetic soft tissue management following two periimplant graft failures: a
      clinical report.
AB  - A 53-year-old man experienced 2 soft tissue graft failures resulting in sizable
      hard and soft tissue defects in the esthetic zone following implant placement. A
      third connective tissue graft surgery was successful in repairing the defect and
      significantly improving soft tissue quality. A screw-retained, interim implant
      prosthesis was instrumental in gradually shaping the soft tissue over the course
      of the 3 surgeries. The interim prosthesis was modified numerous times to achieve
      a balance of esthetics, surgical protection, and gingival contours. The initial
      form of the prosthesis was designed to protect the surgical site and allow space
      for postsurgical edema. In its final form, the tissue side of the interim
      prosthesis pontic was designed to mimic the cross-sectional profile of a natural
      central incisor root but modified to deliver gentle pressure until maximum
      papilla height was achieved. The definitive restoration was fabricated to mimic
      the final design of the interim restoration and gingival architecture. 

PMID- 24029608
TI  - Annual Review of selected dental literature: report of the Committee on
      Scientific Investigation of the American Academy of Restorative Dentistry.

PMID- 24029609
TI  - Width ratios in the anterior maxillary region in a Hungarian population: addition
      to the golden proportion debate.
AB  - STATEMENT OF PROBLEM: In the last 2 decades, several studies have questioned the
      application of the rule of golden proportion in dentistry. PURPOSE: The purpose
      of this study was to test the rule of golden proportion for the maxillary
      anterior region in a population of young, healthy people with excellent oral
      hygiene at the Faculty of Dentistry of the University of Szeged. MATERIAL AND
      METHODS: One hundred and nine participants (36 male, 73 female) were examined, 41
      of whom had previously worn orthodontic appliances. A Canon 450D camera, Canon
      100 mm Macro lens, and a Sigma 140 DG ring flash were used for digital
      documentation. The accreditation photography protocol of the American Academy of
      Cosmetic Dentistry was applied to standardize the images. The width of the teeth
      from the frontal view was measured digitally. Tooth dimension data were collected
      and the Mann-Whitney U test was performed (alpha=.05). RESULTS: The relative
      width of the central incisors, lateral incisors, and canines was 1.6:1:0.85 on
      both sides. The ratios were not influenced by either sex or previous orthodontic
      treatment. CONCLUSIONS: The results demonstrated that, because of the difference
      in canines in this population, the golden proportion in its original form was not
      valid for the maxillary anterior region. Orthodontic treatment does not change
      the dentition toward the golden proportion. The results suggest that the rule of
      golden proportion should not be used for treatment planning without observing
      individual modifying factors.

PMID- 24029610
TI  - Effect of luting agents on the tensile bond strength of glass fiber posts: An in
      vitro study.
AB  - STATEMENT OF PROBLEM: Fiber posts can fail because of loss of retention; and it
      is unknown which luting agent provides the highest bond strength. PURPOSE: The
      purpose of this study was to investigate the tensile bond strength of glass fiber
      posts luted to premolar teeth with 6 resin composite luting agents. MATERIAL AND
      METHODS: Ninety-six single-rooted extracted human mandibular premolars were
      sectioned 2 mm coronal to the most incisal point of the cementoenamel junction.
      Root canals were instrumented and obturated with laterally condensed gutta percha
      and root canal sealer (AH26). Gutta percha was removed from the canals to a depth
      of 8 mm and diameter post spaces with a 1.5 mm were prepared. The specimens were
      divided into the following 6 groups according to the luting agent used (n=16):
      Group V, Variolink II; Group A, RelyX ARC; Group N, Multilink N; Group U, RelyX
      Unicem; Group P, ParaCore; Group F, MultiCore Flow. Each specimen was secured in
      a universal testing machine and a separating load was applied at a rate of 0.5
      mm/min. The forces required to dislodge the posts were recorded. A 1-way analysis
      of variance (ANOVA) was applied to the mean retentive strengths of various cement
      materials (alpha=.05). RESULTS: Significant differences were recorded among the 6
      cement types (P<.001). Three materials provided statistically equivalent mean
      bond strengths (RelyX Unicem, Paracore, and MultiCore Flow) that were
      significantly greater than for the other 3 materials. CONCLUSIONS: Fiber posts
      luted with RelyX Unicem, Paracore, and MultiCore Flow demonstrated significantly
      higher bond strengths.

PMID- 24029611
TI  - Complex mandibular reconstruction after a partial mandibulectomy with a fibula
      free graft: a clinical report.
AB  - This report describes the surgical and prosthetic reconstruction of a partial
      mandibular resection due to an osteomyelitic variant with a free fibula
      microvascular graft, dental implant placement, and reconstruction with a computer
      aided design/computer-aided manufacturing (CAD/CAM) partial fixed dental
      prosthesis. A team composed of a prosthodontist, oral and maxillofacial surgeon,
      and otolaryngologist was required to treat and restore the patient to near normal
      comfort and function. 

PMID- 24029612
TI  - A two-step (altered cast) impression technique in the prosthetic rehabilitation
      of a patient after a maxillectomy: a clinical report.
AB  - This clinical report describes the prosthetic rehabilitation complicated by
      trismus (as a consequence of surgery and radiation therapy) of a patient with an
      acquired maxillary defect, after surgical removal of the right maxillary sinus
      tumor. The patient was restored with a partial removable dental prosthesis with a
      hollow bulb obturator to obtain orofacial rehabilitation and defect obturation.
      Precise obturation requires an accurate impression of the resection defect. A 2
      step impression was performed because of trismus. A primary maxillary impression
      was made with an irreversible hydrocolloid, while a secondary (altered cast)
      impression was made with a silicone material by using the obturator cast
      framework as a tray. In that way an altered cast was produced. Subsequently, an
      obturator prosthesis was processed with a conventional technique. 

PMID- 24029613
TI  - A modified surgical template with dual function.

PMID- 24029614
TI  - Quick and effective custom tray for a feeding obturator.

PMID- 24029615
TI  - Spiritual background and its association with the medical decision of, DNR at
      terminal life stages.
AB  - In recent years personal and clinical dilemmas relating to terminally ill patient
      care medical, decisions have increased significantly. Although understanding the
      patient's medical, nursing and, social background is important, a comprehensive
      appraisal essential for treating the "whole patient" is, incomplete without a
      spirituality assessment. Religious beliefs and practices affect medical and
      health, care decisions and require recognition as a dynamic in coping with
      suffering, loss, life, and death. Taking a spiritual background obtains
      information that is meaningful to the patient's life and may, influence the
      medical decision-making relating to health. A study was undertaken to determine,
      whether assessing the spiritual background influences medical decisions-making
      regarding the use of, DNR. The target population was 46 family-member caregivers
      of non-communicative patients in the Herzog, Hospital Skilled Nursing ward
      located in Jerusalem. The spiritual assessment questionnaire was the, acronym
      FICA (faith, importance, community and addressing). Two-thirds of the families
      were opposed to a determination utilizing do not resuscitate (DNR). Multivariate,
      analysis of the findings found that only religious affiliation was statistically
      significant (p=0.003). The doctors recommend DNR in 67% of the cases while the
      family caregiver accepted this decision in, only 33% of the cases. The hypothesis
      was verified. People who are perceived as being religious or as being greatly
      influenced, by faith/spirituality opposed the recommendation implementing DNR.
      Obtaining a spiritual background assists the physician to understand the patient
      or family spirituality, facilitates sensitivity to value frameworks and
      preferences in making medical and health-related, decisions. 

PMID- 24029616
TI  - Hypertrophic olivary degeneration after pontine hemorrhage: a cause of delayed
      neurological deterioration.

PMID- 24029617
TI  - A validated stability-indicative UPLC method for nilotinib hydrochloride for the
      determination of process-related and degradation impurities.
AB  - A novel stability-indicating ultra performance liquid chromatographic (UPLC)
      method has been developed for quantitative determination of nilotinib
      hydrochloride in active pharmaceutical ingredients along with four impurities
      (imp-1, imp-2, imp-3 and imp-4). The method is applicable to the quantification
      of related compounds and assay of nilotinib hydrochloride drug. Efficient
      chromatographic separation was achieved on a Shim-pack XR-ODS II, 75 * 3.0 mm,
      1.8-um column with a gradient mobile phase combination. Quantification was
      carried at 260 nm at a flow rate of 0.6 mL min(-1). Stress degradation conditions
      were established for nilotinib hydrochloride by subjecting it to acid, base,
      oxidation, humidity, thermal and photolysis. The stress samples were assayed
      against a qualified reference standard and the mass balance was found close to
      97.0%. The developed UPLC method was validated according to the present
      International Conference on Harmonisation guidelines for specificity, detection
      limit, quantitation limit, linearity, accuracy, precision, intermediate precision
      and robustness. The resolution between nilotinib hydrochloride and four potential
      impurities is found to be >2.0. Regression analysis shows as r value (correlation
      coefficient) of >0.999 for nilotinib hydrochloride and four potential impurities.

PMID- 24029618
TI  - An improved liquid chromatography-tandem mass spectrometric method to quantify
      formoterol in human urine.
AB  - Formoterol is a new threshold substance in the prohibited list 2012 according to
      World Anti-Doping Agency. Extracted by ethyl acetate using formoterol-D6 as
      internal standard, formoterol underwent a constant flow rate gradient elution
      separation in reversed-phase liquid chromatography. Subsequently, mass
      spectrometry analysis was conducted by tandem mass spectrometry in the multiple
      reaction monitoring mode. According to the proposed method, a calibration curve
      was constructed in the range of 0.2-500 ng/mL (r(2) = 1) with a limit of
      quantification 0.2 ng/mL. The mean extracted recovery assessed at three different
      concentrations (1, 30 and 100 ng/mL) was more than 80%. The method was validated
      by the analysis of three quality control samples from World Association of Anti
      Doping Scientists. In conclusion, the developed and validated method was
      sensitive, accurate and precise for the quantification of formoterol in human
      urine for doping control purposes. 

PMID- 24029619
TI  - Separation rule of oleanane and ursane pentacyclic triterpenoids isomers from
      nature plants by coordination chromatography.
AB  - Many of oleanolic and ursolic pentacyclic triterpenoid isomers generally coexist.
      There is a small difference in their structures. Based on coordination
      chromatography theory, a reversed-phase high-performance thin-layer
      chromatography (HPLC) method has been investigated for improving the isomers'
      resolution by adding suitable agents in mobile phase, and the separation rule was
      summarized. With the calculation analysis, the space sizes of isomers were in the
      range of 3.77-5.65 A. The total minimum energy in the inclusion of guest and beta
      CD had the biggest reduction, compared with the energy in the simple mixture of
      guest and beta-CD (such as "asiaticoside-B" and "beta-CD," from 196.4406 to
      95.0670 kJ mol(-1)). So, beta-CD (the cavity space size is in the range of 6.00
      6.50 A) and its derivatives were selected as the suitable agents. The experiment
      results showed that the resolution might be improved by adding the hydrophilic
      beta-CD derivatives in mobile phase, such as Glu-beta-CD, when the isomer
      structures carry big hydrophilic groups. 

PMID- 24029620
TI  - Segmentation of dynamic PET images with kinetic spectral clustering.
AB  - Segmentation is often required for the analysis of dynamic positron emission
      tomography (PET) images. However, noise and low spatial resolution make it a
      difficult task and several supervised and unsupervised methods have been proposed
      in the literature to perform the segmentation based on semi-automatic clustering
      of the time activity curves of voxels. In this paper we propose a new method
      based on spectral clustering that does not require any prior information on the
      shape of clusters in the space in which they are identified. In our approach, the
      p-dimensional data, where p is the number of time frames, is first mapped into a
      high dimensional space and then clustering is performed in a low-dimensional
      space of the Laplacian matrix. An estimation of the bounds for the scale
      parameter involved in the spectral clustering is derived. The method is assessed
      using dynamic brain PET images simulated with GATE and results on real images are
      presented. We demonstrate the usefulness of the method and its superior
      performance over three other clustering methods from the literature. The proposed
      approach appears as a promising pre-processing tool before parametric map
      calculation or ROI-based quantification tasks. 

PMID- 24029621
TI  - Slow sinus heart rate as a potential predictive factor of paroxysmal atrial
      fibrillation in stroke patients.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (PAF) is a strong independent risk
      factor for ischemic stroke and is also associated with stroke severity and
      mortality. However, the detection rate of PAF in patients with ischemic stroke is
      limited because they are often asymptomatic or present with sinus rhythm on
      electrocardiograms (ECGs). In the present study, we aimed to identify predictors
      of PAF in stroke patients by continuous ECG monitoring of the heart rate in sinus
      rhythm. METHODS: We enrolled 741 consecutive patients with acute symptomatic
      ischemic stroke who were admitted to our hospital. Exclusion criteria were the
      following: (1) patients with persistent AF, (2) cardiac pacemaker users and (3)
      incomplete clinical investigations. Each patient was subject to 24-hour Holter
      ECG, cardiac monitoring by inpatient telemetry and routine transthoracic
      echocardiography. The minimum and mean sinus heart rates (SHRs) on 24-hour Holter
      ECGs were recorded. The presence of PAF was judged on the basis of previous
      history and cardiac studies during hospitalization. Clinical characteristics of
      the patients with and without PAF were compared, and multiple logistic regression
      analysis was performed to identify the predictors of PAF. RESULTS: Of all
      enrolled patients, 606 (mean age 68.2 years, 63.4% male) were eligible for
      analysis, and the presence of PAF was confirmed in 116 subjects (19.1%). In the
      univariate analysis, the patients with and without PAF showed significant
      differences in age (74.3 vs. 66.7 years, p < 0.001), dyslipidemia (32.8 vs.
      50.4%, p = 0.001), chronic heart failure (16.4 vs. 4.7%, p < 0.001), admission
      National Institute of Health Stroke Scale score (8.5 vs. 6, p < 0.001) and
      absence of vascular etiology (80.2 vs. 54.1%, p < 0.001). Furthermore, the
      minimum and mean SHRs were slower in the patients with than in those without PAF
      (46.5 vs. 54.0 bpm, p < 0.001 and 70.7 vs. 73.8 bpm, p = 0.009, respectively). In
      501 (82.7%) out of 606 patients, minimum SHRs were detected at night (from 9:00
      p.m. to 7:00 a.m.). A minimum SHR was an independent predictive factor of PAF in
      the multivariate analysis (odds ratio 1.08, 95% confidence interval 1.05 - 1.12,
      p < 0.001). CONCLUSIONS: A slow SHR on monitoring ECG is a potential predictive
      factor of PAF in patients with ischemic stroke.

PMID- 24029622
TI  - Using prize-based incentives to enhance daily interactive voice response (IVR)
      compliance: a feasibility study.
AB  - This study examined the feasibility of a prize-based contingency-management (CM)
      approach to encourage interactive voice response (IVR) compliance in a cocaine
      treatment study and explored the association between IVR call rate and outcome
      during a cocaine abstinence-induction trial. Subjects called into the IVR system
      daily to complete a brief interview assessing cocaine use for the past 24hours.
      One group earned $1 for each call; the other earned one draw per call from a
      "prize bowl" with a range of awards. Abstinence was rewarded according to a high
      value voucher incentive schedule, which was the same for both groups, and
      confirmed by thrice-weekly urine testing at clinic visits. Odds of calling were
      4.7 times greater (95% CI: 1.23, 17.91) in the prize-CM group than in the fixed
      dollar CM group. In addition, the percentage of IVR calls was significantly
      associated with abstinence achievement, chi(2) (1)=5.147, p<.023. The use of
      prize-based CM to increase the use of IVR is feasible and deserves examination as
      an innovation for helping participants engage in treatment. 

PMID- 24029623
TI  - Translating SBIRT to public school settings: an initial test of feasibility.
AB  - Public schools are not traditional locations where screening, brief motivational
      counseling intervention and referral to treatment (SBIRT) are provided. This
      translational research study aimed to test the feasibility of conducting SBIRT in
      two urban New York schools and to examine its economic sustainability. In Spring
      2012, 248 students were screened during non-academic classes: 42% of them (n=105)
      reported substance use (versus 28% reported in school-wide, paper anonymous
      survey). All but one of the positively screened students voluntarily accepted one
      or more brief intervention sessions and two students were referred to treatment.
      This school-based SBIRT model did not interfere with academic activities, was
      feasible to implement, and was attractive to students, teachers and
      administration. The data offer clear indication that further effectiveness
      testing is warranted and potentially valuable, however the sustainability of this
      model was not supported due to our lack of obtaining insurance information,
      authorization and reimbursement. 

PMID- 24029624
TI  - Short-term efficacy of nicotine replacement therapy for smoking cessation in
      adolescents: a randomized controlled trial.
AB  - The aim of this randomized, double-blind placebo-controlled clinical trial is to
      test the efficacy and safety of nicotine replacement therapy (NRT) in promoting
      end-of-treatment abstinence among adolescents and whether this relation is
      moderated by medication compliance. Participants (N=257, age: 16.7+/-1.13 years)
      attended an information meeting followed by a 6- or 9-week treatment. Self
      reported smoking cessation, compliance, and side effects were measured by means
      of online questionnaires. Intent-to-treat analyses showed that independent of
      compliance, NRT is effective in promoting abstinence rates after 2 weeks
      (OR=2.02, 95% CI=1.11-3.69), but not end-of-treatment abstinence. However, end-of
      treatment abstinence rates significantly increased in high-compliant (OR=1.09,
      95% CI=1.01-1.17) and not in low-compliant participants. No serious adverse
      events were found. Future research is warranted to disentangle the process
      involving the decrease in abstinence rates and compliance rates from the third
      week after the quit date onwards.

PMID- 24029626
TI  - Causes of a nationwide rubella outbreak in Japan, 2012-2013.

PMID- 24029625
TI  - Development of a personalized bidirectional text messaging tool for HIV adherence
      assessment and intervention among substance abusers.
AB  - We describe the development of a two-way text messaging intervention tool for
      substance users who are non-adherent with HIV medications, and examine message
      flow data for feasibility and acceptability. The assessment and intervention
      tool, TxText, is fully automated, sending participants mood, substance use, and
      medication adherence queries by text message. Participants respond, the tool
      recognizes the category of response, and sends the personalized intervention
      message that participants designed in return. In 10months, the tool sent 16,547
      messages (half initial, half follow-up) to 31 participants assigned to the TxText
      condition, who sent 6711 messages in response to the initial messages. Response
      rates to substance use (n=2370), medication (n=2918) and mood (n=4639) queries
      were 67, 69, and 64%, respectively. Responses indicating medication adherence,
      abstinence from substances, and good moods were more common than negative
      responses. The TxText tool can send messages daily over a 3month period, receive
      responses, and decode them to deliver personalized affirming or intervention
      messages. While we await the outcomes of a pilot randomized trial, the process
      analysis shows that TxText is acceptable and feasible for substance abusers with
      HIV, and may serve as a complement to HIV medical care. 

PMID- 24029627
TI  - Prefibrillar tau oligomers in mild cognitive impairment and Alzheimer's disease.
AB  - BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder
      characterized by the accumulation of extracellular amyloid-beta peptide and
      intracellular tau. Here, we review data suggesting that prefibrillar tau
      oligomers mediate cognitive decline early in the disease. OBJECTIVE: It was our
      aim to study the presence of tau-positive pretangle neurons and correlate
      findings with cognitive test scores. METHODS: Pretangle antibodies (TOC1 and
      pS422) were applied to tissue containing cholinergic basal forebrain neurons from
      people who died with a premortem clinical diagnosis of no cognitive impairment,
      mild cognitive impairment and AD. RESULTS: Data lend support to the concept that
      tau oligomers are the toxic form of tau, that non-fibillar tau relates to
      cognitive dysfunction and that the earliest pretangle pathology occurs in
      neuritic processes. CONCLUSIONS: Clinicopathological findings highlight the
      importance of studying tau modifications in neuronal soma and neuritic processes,
      which may be the earliest pathological lesions that correlate with cognitive
      status.

PMID- 24029628
TI  - Pattern and predictors of volumetric change of parotid glands during intensity
      modulated radiotherapy.
AB  - OBJECTIVE: To describe the pattern and predictors of volumetric change of parotid
      glands during intensity modulated radiotherapy (IMRT) for oropharyngeal cancer.
      METHODS: A cohort of patients undergoing weekly CT scans during dose-painted IMRT
      was considered. The parotid glands were contoured at the time of treatment
      planning (baseline) and on all subsequent scans. For a given patient, the parotid
      glands were labelled as higher (H) and lower (L), based on the mean dose at
      planning. The volume of each gland was determined for each scan and the percent
      change from baseline computed. Data were fit to both linear and quadratic
      functions. The role of selected covariates was assessed with both logistic
      regression and pair-wise comparison between the sides. The analyses were
      performed considering the whole treatment duration or each separate half.
      RESULTS: 85 patients, 170 glands and 565 scans were analysed. For all parotids
      except one, the quadratic function provided a better fit than the linear one.
      Moreover, according to both the logistic regression and pair-wise comparison, the
      cumulative mean dose of radiation is independently correlated with the parotid
      shrinkage during the first but not the second half of the treatment. Conversely,
      age and weight loss are predictors of relative parotid shrinkage during the
      entire course of the treatment. CONCLUSION: Parotid gland shrinkage during IMRT
      is not linear. Age, weight loss and radiation dose independently predict parotid
      shrinkage during a course of IMRT. ADVANCES IN KNOWLEDGE: The present study adds
      to the pathophysiology of parotid shrinkage during radiotherapy.

PMID- 24029629
TI  - Dynamic contrast-enhanced CT in suspected lung cancer: quantitative results.
AB  - OBJECTIVES: To examine whether dynamic contrast-enhanced CT (DCE-CT) could be
      used to characterise and safely distinguish between malignant and benign lung
      tumours in patients with suspected lung cancer. METHODS: Using a quantitative
      approach to DCE-CT, two separate sets of regions of interest (ROIs) in tissues
      were placed in each tumour: large ROIs over the entire tumour and small ROIs over
      the maximally perfused parts of the tumour. Using mathematical modelling
      techniques and dedicated perfusion software, this yielded a plethora of results.
      RESULTS: First, because of their non-normal distribution, DCE-CT measurements
      must be analysed using log scale data transformation. Second, there were highly
      significant differences between large ROI and small ROI measurements (p<0.001).
      Thus, the ROI method used in a given study should always be specified in advance.
      Third, neither quantitative parameters (blood flow and blood volume) nor semi
      quantitative parameters (peak enhancement) could be used to distinguish between
      malignant and benign tumours. This was irrespective of the method of
      quantification used for large ROIs (0.13<p<0.76) and small ROIs (0.084<p<0.31).
      Fourth, although there were no indications of systematic reproducibility bias,
      the 95% limits of agreement were so broad that the risk of disagreement between
      the measurements could affect the clinical use of the measurements. This lack of
      reproducibility should be addressed. CONCLUSION AND ADVANCES IN KNOWLEDGE: A
      quantitative approach to DCE-CT is not a clinically usable method for
      characterising lung tumours.

PMID- 24029630
TI  - The features of breast lymphoma on MRI.
AB  - OBJECTIVE: To investigate the morphological features of breast lymphoma (BL) on
      MRI. METHODS: MRI features of 20 patients with BL (12 primary and 8 secondary)
      were reviewed according to Breast Imaging-Reporting and Data System categories.
      RESULTS: 19 cases were unilateral and 1 was bilateral. According to the enhanced
      images, of the 20 cases, BL presented as a mass in 11 (55%), as an enhancement
      with no mass effect in 7 (35%) and as a mass and mixed enhancement with no mass
      effect in 2 (10%). There were 38 masses and 44 lesions with no mass effect in our
      study. All lesions showed mild heterogeneous internal enhancement. For lesions
      with mass effect, the margins were smooth in 32% (12/38) and irregular in 68%
      (26/38); and the shape was oval in 87% (32/38). Kinetic curve assessment (13
      cases, 38 lesions) revealed that the average initial rise rate was 104%. The type
      II enhancement curve appeared in 55% (21/38) of lesions. No significant
      differences between the primary and secondary BL were observed for any of the MRI
      features. CONCLUSION: BL mostly appeared oval with irregular margins showing mild
      heterogeneous internal enhancement and/or as enhanced lesions with no mass effect
      with mild heterogeneous internal enhancement. ADVANCES IN KNOWLEDGE: Some special
      features on MRI are useful for the diagnosis of BL.

PMID- 24029631
TI  - Estimation of percentage breast tissue density: comparison between digital
      mammography (2D full field digital mammography) and digital breast tomosynthesis
      according to different BI-RADS categories.
AB  - OBJECTIVE: To compare breast density estimated from two-dimensional full-field
      digital mammography (2D FFDM) and from digital breast tomosynthesis (DBT)
      according to different Breast Imaging-Reporting and Data System (BI-RADS)
      categories, using automated software. METHODS: Institutional review board
      approval and written informed patient consent were obtained. DBT and 2D FFDM were
      performed in the same patients to allow within-patient comparison. A total of 160
      consecutive patients (mean age: 50+/-14 years; mean body mass index: 22+/-3) were
      included to create paired data sets of 40 patients for each BI-RADS category.
      Automatic software (MedDensity((c)), developed by Giulio Tagliafico) was used to
      compare the percentage breast density between DBT and 2D FFDM. The estimated
      breast percentage density obtained using DBT and 2D FFDM was examined for
      correlation with the radiologists' visual BI-RADS density classification.
      RESULTS: The 2D FFDM differed from DBT by 16.0% in BI-RADS Category 1, by 11.9%
      in Category 2, by 3.5% in Category 3 and by 18.1% in Category 4. These
      differences were highly significant (p<0.0001). There was a good correlation
      between the BI-RADS categories and the density evaluated using 2D FFDM and DBT
      (r=0.56, p<0.01 and r=0.48, p<0.01, respectively). CONCLUSION: Using DBT, breast
      density values were lower than those obtained using 2D FFDM, with a non-linear
      relationship across the BI-RADS categories. These data are relevant for clinical
      practice and research studies using density in determining the risk. ADVANCES IN
      KNOWLEDGE: On DBT, breast density values were lower than with 2D FFDM, with a non
      linear relationship across the classical BI-RADS categories.

PMID- 24029632
TI  - Influence of chronic hyperglycemia on cerebral microvascular remodeling: an in
      vivo study using perfusion computed tomography in acute ischemic stroke patients.
AB  - BACKGROUND AND PURPOSE: To investigate the effect of chronic hyperglycemia on
      cerebral microvascular remodeling using perfusion computed tomography. METHODS:
      We retrospectively identified 26 patients from our registry of 2453 patients who
      underwent a perfusion computed tomographic study and had their hemoglobin A1c
      (HbA1c) measured. These 26 patients were divided into 2 groups: those with
      HbA1c>6.5% (n=15) and those with HbA1c<=6.5% (n=11). Perfusion computed
      tomographic studies were processed using a delay-corrected, deconvolution-based
      software. Perfusion computed tomographic values were compared between the 2
      patient groups, including mean transit time, which relates to the cerebral
      capillary architecture and length. RESULTS: Mean transit time values in the
      nonischemic cerebral hemisphere were significantly longer in the patients with
      HbA1c>6.5% (P=0.033), especially in the white matter (P=0.005). Significant
      correlation (R=0.469; P=0.016) between mean transit time and HbA1c level was
      observed. CONCLUSIONS: Our results from a small sample suggest that chronic
      hyperglycemia may be associated with cerebral microvascular remodeling in humans.
      Additional prospective studies with larger sample size are required to confirm
      this observation.

PMID- 24029633
TI  - Obstacles and solutions in the implementation of telestroke: billing, licensing,
      and legislation.

PMID- 24029634
TI  - Ancel Keys Lecture: Adventures (and misadventures) in understanding (and
      reducing) disparities in stroke mortality.

PMID- 24029636
TI  - Rapid-thermal-annealing surface treatment for restoring the intrinsic properties
      of graphene field-effect transistors.
AB  - Graphene field-effect transistors (GFETs) were fabricated by photolithography and
      lift-off processes, and subsequently heated in a rapid-thermal-annealing (RTA)
      apparatus at temperatures (T(A)) from 200 to 400  degrees C for 10 min under
      nitrogen to eliminate the residues adsorbed on the graphene during the GFET
      fabrication processes. Raman-scattering, current-voltage (I-V), and sheet
      resistance measurements showed that, after annealing at 250  degrees C, graphene
      in GFETs regained its intrinsic properties, such as very small intensity ratios
      of D to G and G to 2D Raman bands, a symmetric I-V curve with respect to ~0 V,
      and very low sheet resistance. Atomic force microscopy images and height profiles
      also showed that the surface roughness of graphene was almost minimized at T(A) =
      250  degrees C. By annealing at 250  degrees C, the electron and hole mobilities
      reached their maxima of 4587 and 4605 cm(2) V(-1) s(-1), respectively, the
      highest ever reported for chemical-vapor-deposition-grown graphene. Annealing was
      also performed under vacuum or hydrogen, but this was not so effective as under
      nitrogen. These results suggest that the RTA technique is very useful for
      eliminating the surface residues of graphene in GFETs, in that it employs a
      relatively low thermal budget of 250  degrees C and 10 min.

PMID- 24029635
TI  - FTY720 ameliorates acute ischemic stroke in mice by reducing thrombo-inflammation
      but not by direct neuroprotection.
AB  - BACKGROUND AND PURPOSE: Lymphocytes are important players in the pathophysiology
      of acute ischemic stroke. The interaction of lymphocytes with endothelial cells
      and platelets, termed thrombo-inflammation, fosters microvascular dysfunction and
      secondary infarct growth. FTY720, a sphingosine-1-phosphate receptor modulator,
      blocks the egress of lymphocytes from lymphoid organs and has been shown to
      reduce ischemic neurodegeneration; however, the underlying mechanisms are
      unclear. We investigated the mode of FTY720 action in models of cerebral
      ischemia. METHODS: Transient middle cerebral artery occlusion (tMCAO) was induced
      in wild-type and lymphocyte-deficient Rag1(-/-) mice treated with FTY720 (1
      mg/kg) or vehicle immediately before reperfusion. Stroke outcome was assessed 24
      hours later. Immune cells in the blood and brain were counted by flow cytometry.
      The integrity of the blood-brain barrier was analyzed using Evans Blue dye.
      Thrombus formation was determined by immunohistochemistry and Western blot, and
      was correlated with cerebral perfusion. RESULTS: FTY720 significantly reduced
      stroke size and improved functional outcome in wild-type mice on day 1 and day 3
      after transient middle cerebral artery occlusion. This protective effect was lost
      in lymphocyte-deficient Rag1(-/-) mice and in cultured neurons subjected to
      hypoxia. Less lymphocytes were present in the cerebral vasculature of FTY720
      treated wild-type mice, which in turn reduced thrombosis and increased cerebral
      perfusion. In contrast, FTY720 was unable to prevent blood-brain barrier
      breakdown and transendothelial immune cell trafficking after transient middle
      cerebral artery occlusion. CONCLUSIONS: Induction of lymphocytopenia and
      concomitant reduction of microvascular thrombosis are key modes of FTY720 action
      in stroke. In contrast, our findings in Rag1(-/-) mice and cultured neurons argue
      against direct neuroprotective effects of FTY720.

PMID- 24029637
TI  - Diclofenac removal in urine using strong-base anion exchange polymer resins.
AB  - One of the major sources of pharmaceuticals in the environment is wastewater
      effluent of which human urine contributes the majority of pharmaceuticals. Urine
      source separation has the potential to isolate pharmaceuticals at a higher
      concentration for efficient removal as well as produce a nutrient byproduct. This
      research investigated the efficacy of using strong-base anion exchange polymer
      resins to remove the widely detected and abundant pharmaceutical, diclofenac,
      from synthetic human urine under fresh and ureolyzed conditions. The majority of
      experiments were conducted using a strong-base, macroporous, polystyrene resin
      (Purolite A520E). Ion-exchange followed a two-step removal rate with rapid
      removal in 1 h and equilibrium removal in 24 h. Diclofenac removal was >90% at a
      resin dose of 8 mL/L in both fresh and ureolyzed urine. Sorption of diclofenac
      onto A520E resin was concurrent with desorption of an equivalent amount of
      chloride, which indicates the ion-exchange mechanism is occurring. The presence
      of competing ions such as phosphate and citrate did not significantly impact
      diclofenac removal. Comparisons of three polystyrene resins (A520E, Dowex 22,
      Dowex Marathon 11) as well as one polyacrylic resin (IRA958) were conducted to
      determine the major interactions between anion exchange resin and diclofenac. The
      results showed that polystyrene resins provide the highest level of diclofenac
      removal due to electrostatic interactions between quaternary ammonium functional
      groups of resin and carboxylic acid of diclofenac and non-electrostatic
      interactions between resin matrix and benzene rings of diclofenac. Diclofenac was
      effectively desorbed from A520E resin using a regeneration solution that
      contained 4.5% (m/m) NaCl in an equal-volume mixture of methanol and water. The
      greater regeneration efficiency of the NaCl/methanol-water mixture over the
      aqueous NaCl solution supports the importance of non-electrostatic interactions
      between resin matrix and benzene rings of diclofenac. Experiments with
      ketoprofen, in addition to diclofenac, suggest that polystyrene anion exchange
      resins can be used to selectively remove other acidic pharmaceuticals from urine.

PMID- 24029638
TI  - A specific genomic organization and a novel promoter sequence for both ZP2 and
      ZP3 gene expressions in the Pingxiang red transparent crucian carp, Carassius
      auratus var. pingxiangnensis.
AB  - We cloned the full-length cDNA of ZP2 from Carassius auratus var. Pingxiangnensis
      (CaP_ZP2) and identified a cluster of three ZP genes through its DNA walker.
      These three genes, CaP_ZP3.1, CaP_ZP2 and CaP_ZP3.2 were located within a
      10,855bp region and each comprised of eight exons spanning 1348bp, 1638bp and
      1348bp, respectively. Protein bands of egg membrane between 40 and 70kDa were in
      concordance with the deduced amino acid of these three CaP_ZP genes cDNA and with
      their molecular mass. This is the first report that two CaP_ZP3 genes were
      separated by CaP_ZP2 gene. A novel sequence of 1097bp, located between CaP_ZP2
      and CaP_ZP3.2, was inserted into the modified pAcGFP1-1 vector in the forward and
      reverse directions. Results showed that individual sequence served as promoters
      utilizing common regulatory elements in the forward and reverse directions for
      both CaP_ZP2 and CaP_ZP3.2 gene expressions. In situ hybridization against
      CaP_ZP2 confirmed that a strong positive signal was detected in the early
      development oocytes. Similarly, real-time PCR results also showed that CaP_ZP2
      transcription increased mainly in a 4-8month ovary, but was decreased
      dramatically in a 9-12month ovary. 

PMID- 24029639
TI  - Rapid progression of unilateral moyamoya disease in a patient with a family
      history and an RNF213 risk variant.

PMID- 24029640
TI  - Volume-based parameters measured by using FDG PET/CT in patients with stage I
      NSCLC treated with stereotactic body radiation therapy: prognostic value.
AB  - PURPOSE: To evaluate the prognostic importance and predictive performance of
      volume-based parameters of fluorine 18 fluorodeoxyglucose (FDG) positron emission
      tomography (PET)/computed tomography (CT) in patients with stage I non-small cell
      lung cancer (NSCLC) after stereotactic body radiation therapy (SBRT). MATERIALS
      AND METHODS: This study had institutional review board approval. All patients
      gave written informed consent for SBRT as well as for future anonymous use of
      clinical data. Data in 88 patients with stage I NSCLC (68 patients with T1N0M0
      disease and 20 with T2aN0M0 disease) who had undergone FDG PET/CT and then SBRT
      were retrospectively evaluated. Seventy-seven tumors were histopathologically
      proved (48 adenocarcinomas, 24 squamous cell carcinomas, and five unspecified non
      small cell carcinomas), and the remaining 11 tumors were diagnosed clinically
      without histopathologic diagnosis. Maximum standardized uptake value (SUVmax),
      metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were analyzed.
      The MTV of the primary tumor was calculated as all voxels with an SUV of 2.5 or
      greater within the isocontour line, while TLG was calculated as MTV multiplied by
      the average SUV, by using fixed thresholds of either 50% (TLG50) or 60% (TLG60)
      of the maximum intratumoral FDG activity. The prognostic importance of PET
      parameters and other clinicopathologic variables (age, sex, tumor size, tumor
      location [peripheral or central], and biologically effective dose) was assessed
      by using Cox proportional hazards regression analysis of overall survival (OS)
      and disease-free survival (DFS) for both univariate and multiple-variable
      analyses. RESULTS: The median follow-up period was 33 months. At 3 years, OS and
      DFS were 70.0% and 49.7%, respectively. In the univariate analyses, SUVmax (P =
      .001), MTV (P = .002), TLG50 (P = .001), and TLG60 (P < .001) were found to be
      significantly associated with DFS. In multiple variable analysis, these
      parameters were also significantly associated with DFS (P = .011 for SUVmax, P =
      .010 for MTV, P = .004 for TLG50, and P = .005 for TLG60). Only volumetric
      parameters (MTV, TLG50, and TLG60) were significant indicators of DFS in patients
      with tumors larger than 3 cm. CONCLUSION: SUVmax, MTV, and TLG at FDG PET/CT have
      a prognostic role for patients with NSCLC treated with SBRT. When tumors are
      larger than 3 cm, only MTV and TLG are predictive of DFS.

PMID- 24029641
TI  - Invasive breast carcinoma: influence of prognosis and patient-related factors on
      kinetic MR imaging characteristics.
AB  - PURPOSE: To retrospectively compare the kinetic magnetic resonance (MR) imaging
      characteristics of invasive breast carcinomas with both prognostic tumoral and
      patient-related parameters. MATERIALS AND METHODS: This HIPAA-compliant
      retrospective study was approved by the institutional review board, and informed
      consent was waived. From January 2008 to January 2011, 273 consecutive women
      (mean age, 55 years; range, 23-83 years) with invasive breast cancers who had
      undergone MR imaging were selected. The kinetic curves were retrospectively
      classified according to the Breast Imaging Reporting and Data System lexicon.
      Initial enhancement and maximal enhancement percentages, time to peak
      enhancement, and the signal enhancement ratio were calculated for each lesion.
      Kinetic characteristics were compared according to tumoral parameters (size,
      pathologic type, grade, hormone receptor status, and c-erbB-2 status) and patient
      parameters (menopausal status, personal history of breast carcinoma) by means of
      univariate and then multivariate analysis by using false-discovery-rate
      statistics. RESULTS: Lesions in menopausal patients exhibited less suspicious
      quantitative and qualitative characteristics than lesions in nonmenopausal
      patients. There was an independent association between the kinetic
      characteristics and menopausal status, with an odds ratio of 2.94 for the lack of
      rapid initial contrast material uptake and of 2.38 for the lack of washout in
      menopausal patients as compared with nonmenopausal patients. The odds ratio was
      4.00 for not having rapid initial contrast material uptake in patients with a
      personal history of ipsilateral breast cancer. CONCLUSION: Kinetic data in
      invasive breast cancer are associated with the patient's menopausal status, with
      a typical kinetic pattern of malignancy being less common in menopausal patients.

PMID- 24029642
TI  - Quality of reporting noninferiority/similarity in research studies of diagnostic
      imaging.
AB  - PURPOSE: To evaluate the quality of reporting noninferiority/similarity in
      research studies of diagnostic imaging. MATERIALS AND METHODS: All 661 original
      research articles published in Radiology and European Radiology in 2012 were hand
      searched to find original studies of diagnostic imaging that included a claim of
      noninferiority/similarity as a study conclusion. A separate MEDLINE search was
      performed to identify original studies of diagnostic imaging designed as
      noninferiority studies, defined as studies at least embodying noninferiority
      margin, published in English between April 2007 and December 2012. Thirty-eight
      articles in the first category and 30 in the second category reporting a total of
      31 noninferiority studies were finally collected after screening for eligibility.
      The quality of the reported analytic methodology was evaluated largely according
      to the extended Consolidated Standards of Reporting Trials, or CONSORT, statement
      to cover noninferiority studies. In the 31 designated noninferiority studies, the
      authors evaluated the following key areas of compliance required for proper
      reporting: noninferiority margin defined and justification provided, sample size
      calculated according to noninferiority methodology, and use of proper statistical
      analysis. RESULTS: Of the 38 studies concluding noninferiority/similarity, one
      study (3%) used proper analytic method. Twenty-nine of the 38 studies (76%), 28
      of which also omitted sample size estimation, claimed noninferiority/similarity
      for P >= .05 from conventional two-sided superiority testing. Of the 31
      designated noninferiority studies, seven (23%) fulfilled the requirements for
      proper reporting. Justification for noninferiority margin was provided in 15 of
      the 31 studies (48%). Proper sample size estimation was done in 14 of the 31
      studies (45%). CONCLUSION: The quality of reporting noninferiority/similarity in
      recently published research studies of diagnostic imaging was deficient.

PMID- 24029643
TI  - Increased number of microinfarcts in Alzheimer disease at 7-T MR imaging.
AB  - PURPOSE: To assess the prevalence and number of cortical microinfarcts in
      patients with Alzheimer disease (AD) by using a 7-T magnetic resonance (MR)
      imaging system, to assess the independent association of cortical microinfarcts
      with cognitive dysfunction, and to investigate potential confounding effects of
      the coexisting presence of cerebral amyloid angiopathy (CAA). MATERIALS AND
      METHODS: The local institutional review board approved this study. In all cases,
      informed consent was obtained. High-spatial-resolution fluid-attenuated inversion
      recovery and T2*-weighted images were acquired in 14 AD patients and 18 control
      subjects to assess the presence of microinfarcts and microbleeds. Presence of CAA
      was assessed according to the Boston criteria. Image analysis was performed
      independently by two reviewers. Mann-Whitney U test was performed to assess
      differences in number of microinfarcts between groups. Negative binomial
      regression models were used to assess the association between diagnosis of AD and
      diagnosis of CAA and number of microinfarcts, between diagnosis of AD and number
      of microbleeds and number of microinfarcts, and between cognitive function and
      number of microinfarcts, all corrected for age and sex. RESULTS: Interobserver
      agreement was excellent for detecting microinfarcts (kappa = 0.91) (P < .001).
      Patients with AD demonstrated higher number (P = .005) of microinfarcts (mean,
      7.2) compared with control subjects (mean, 1.8). Negative binomial regression
      models showed an independent association between AD and number of microinfarcts
      (P = .006) and a trend for CAA and microinfarcts (P = .052). A negative
      correlation was found between cognitive function and the number of microinfarcts
      (P = .009). CONCLUSION: Patients with AD show more microinfarcts than do control
      subjects, the number of microinfarcts correlates with global cognitive
      performance, and the presence of microinfarcts was mainly AD rather than CAA
      related.

PMID- 24029644
TI  - Two-view versus single-view shear-wave elastography: comparison of observer
      performance in differentiating benign from malignant breast masses.
AB  - PURPOSE: To determine whether two-view shear-wave elastography (SWE) improves the
      performance of radiologists in differentiating benign from malignant breast
      masses compared with single-view SWE. MATERIALS AND METHODS: This prospective
      study was conducted with institutional review board approval, and written
      informed consent was obtained. B-mode ultrasonographic (US) and orthogonal SWE
      images were obtained for 219 breast masses (136 benign and 83 malignant; mean
      size, 14.8 mm) in 219 consecutive women (mean age, 47.9 years; range, 20-78
      years). Five blinded radiologists independently assessed the likelihood of
      malignancy for three data sets: B-mode US alone, B-mode US and single-view SWE,
      and B-mode US and two-view SWE. Interobserver agreement regarding Breast Imaging
      Reporting and Data System (BI-RADS) category and the area under the receiver
      operating characteristic curve (AUC) of each data set were compared. RESULTS:
      Interobserver agreement was moderate (kappa = 0.560 +/- 0.015 [standard error of
      the mean]) for BI-RADS category assessment with B-mode US alone. When SWE was
      added to B-mode US, five readers showed substantial interobserver agreement
      (kappa = 0.629 +/- 0.017 for single-view SWE; kappa = 0.651 +/- 0.014 for two
      view SWE). The mean AUC of B-mode US was 0.870 (range, 0.855-0.884). The AUC of B
      mode US and two-view SWE (average, 0.928; range, 0.904-0.941) was higher than
      that of B-mode US and single-view SWE (average, 0.900; range, 0.890-0.920), with
      statistically significant differences for three readers (P <= .003). CONCLUSION:
      The performance of radiologists in differentiating benign from malignant breast
      masses was improved when B-mode US was combined with two-view SWE compared with
      that when B-mode US was combined with single-view SWE.

PMID- 24029645
TI  - Radiogenomics of clear cell renal cell carcinoma: associations between CT imaging
      features and mutations.
AB  - PURPOSE: To investigate associations between computed tomographic (CT) features
      of clear cell renal cell carcinoma (RCC) and mutations in VHL, PBRM1, SETD2,
      KDM5C, or BAP1 genes. MATERIALS AND METHODS: The institutional review board
      approved this retrospective, hypothesis-generating study of 233 patients with
      clear cell RCC and waived the informed consent requirement. The study was HIPAA
      compliant. Three radiologists independently reviewed pretreatment CT images of
      all clear cell RCCs without knowledge of their genomic profile. One radiologist
      measured largest diameter and enhancement parameters of each clear cell RCC.
      Associations between CT features and mutations in VHL, PBRM1, SETD2, KDM5C, and
      BAP1 genes were tested by using the Fisher exact test. Associations between
      mutations and size and enhancement were assessed by using the independent t test.
      Interreader agreement was calculated by using the Fleiss kappa. RESULTS: Mutation
      frequencies among clear cell RCCs were as follows: VHL, 53.2% (124 of 233);
      PBRM1, 28.8% (67 of 233); SETD2, 7.3% (17 of 233); KDM5C, 6.9% (16 of 233); and
      BAP1, 6.0% (14 of 233). Mutations of VHL were significantly associated with well
      defined tumor margins (P = .013), nodular tumor enhancement (P = .021), and gross
      appearance of intratumoral vascularity (P = .018). Mutations of KDM5C and BAP1
      were significantly associated with evidence of renal vein invasion (P = .022 and
      .046, respectively). The genotype of solid clear cell RCC differed significantly
      from the genotype of multicystic clear cell RCC. While mutations of SETD2, KDM5C,
      and BAP1 were absent in multicystic clear cell RCC, mutations of VHL (P = .016)
      and PBRM1 (P = .017) were significantly more common among solid clear cell RCC.
      Interreader agreement for CT feature assessments ranged from substantial to
      excellent (kappa = 0.791-0.912). CONCLUSION: This preliminary radiogenomics
      analysis of clear cell RCC revealed associations between CT features and
      underlying mutations that warrant further investigation and validation.

PMID- 24029646
TI  - MR selective flow-tracking cartography: a postprocessing procedure applied to
      four-dimensional flow MR imaging for complete characterization of cranial dural
      arteriovenous fistulas.
AB  - PURPOSE: To assess the feasibility of a selective flow-tracking cartographic
      procedure applied to four-dimensional (4D) flow imaging and to demonstrate its
      usefulness in the characterization of dural arteriovenous fistulas (DAVFs).
      MATERIALS AND METHODS: Institutional review board approval was obtained, and all
      patients provided written informed consent. Eight patients (nine DAVFs) underwent
      3.0-T magnetic resonance (MR) imaging and digital subtraction angiography (DSA).
      Imaging examinations were performed within 24 hours of each other. 4D flow MR
      imaging was performed by using a 4D radial phase-contrast vastly undersampled
      isotropic projection reconstruction pulse sequence with an isotropic spatial
      resolution of 0.86 mm (5 minutes 35 seconds). Two radiologists independently
      reviewed images from MR flow-tracking cartography and reported the location of
      arterial feeder vessels and the venous drainage type and classified DAVFs
      according to the risk of rupture (Cognard classification). These results were
      compared with those at DSA. Quadratic weighted kappa statistics with their 95%
      confidence intervals (CIs) were used to test intermodality agreement in the
      identification of arterial feeder vessels, draining veins, and Cognard
      classification. RESULTS: Interreader agreement for shunt location on MR images
      was perfect (kappa = 1), with good-to-excellent interreader agreement for
      arterial feeder vessel identification (kappa = 0.97; 95% CI = 0.92, 1.0), and
      matched in all cases with shunt location defined at DSA. There was good-to
      excellent agreement between MR cartography and DSA in the definition of the main
      feeding arteries (kappa = 0.92; 95% CI = 0.83, 1.0), presence of retrograde flow
      in dural sinuses (kappa = 1), presence of retrograde cortical venous drainage
      (kappa = 1), presence of venous ectasia (kappa = 1), and final Cognard
      classification of DAVFs (kappa = 1, standard error = 0.35). CONCLUSION: MR
      selective flow-tracking cartography enabled the noninvasive characterization of
      cranial DAVFs.

PMID- 24029647
TI  - Carpet lesions detected at CT colonography: clinical, imaging, and pathologic
      features.
AB  - PURPOSE: To describe carpet lesions (laterally spreading tumors >= 3 cm) detected
      at computed tomographic (CT) colonography, including their clinical, imaging, and
      pathologic features. MATERIALS AND METHODS: The imaging reports for 9152
      consecutive adults undergoing initial CT colonography at a tertiary center were
      reviewed in this HIPAA-compliant, institutional review board-approved
      retrospective study to identify all potential carpet lesions detected at CT
      colonography. Carpet lesions were defined as morphologically flat, laterally
      spreading tumors 3 cm or larger. For those patients with neoplastic carpet
      lesions, CT colonography studies were analyzed to determine maximal lesion width
      and height, oral contrast material coating, segmental location, and computer
      aided detection (CAD) findings. Demographic data and details of clinical
      treatment in these patients were reviewed. RESULTS: Eighteen carpet lesions in 18
      patients (0.2%; mean age, 67.1 years; eight men, 10 women) were identified and
      were subsequently confirmed at colonoscopy and pathologic examination among 20
      potential flat masses (>=3 cm) prospectively identified at CT colonography (there
      were two nonneoplastic rectal false-positive findings). No additional neoplastic
      carpet lesions were found in the cohort undergoing colonoscopy after CT
      colonography and/or surgery (there were no false-negatives). Mean lesion width
      was 46.5 mm (range, 30-80 mm); mean lesion height was 7.9 mm (range, 4-14 mm).
      Surface retention of oral contrast material was noted in all 18 cases. All but
      two lesions were located in the distal rectosigmoid or proximal right colon. At
      CAD, 17 (94.4%) lesions were detected (mean, 6.2 CAD marks per lesion). Sixteen
      lesions (88.9%) demonstrated advanced histologic features, including a villous
      component (n = 11), high-grade dysplasia (n = 4), and invasive cancer (n = 5).
      Sixteen patients (88.9%) required surgical treatment for complete excision.
      CONCLUSION: CT colonography can effectively depict carpet lesions. Common
      features in this series included older patient age, rectal or cecal location,
      surface coating with oral contrast material, multiple CAD hits, advanced yet
      typically benign histologic features, and surgical treatment.

PMID- 24029648
TI  - How influential is the duration of contrast material bolus injection in perfusion
      CT? evaluation in a swine model.
AB  - PURPOSE: To analyze the effect of the duration of contrast material bolus
      injection on perfusion values in a swine model by using the maximum slope method.
      MATERIALS AND METHODS: This study was approved by the institutional animal care
      committee. Twenty pigs (weight range, 63-77 kg) underwent dynamic volume computed
      tomography (CT) of the kidneys during suspended respiration. Before the CT
      examination, a miniature cuff-shaped ultrasonographic flow probe encircling the
      right renal artery was surgically implanted in each pig to obtain true perfusion
      values. Two sequential perfusion CT series were performed in 30 seconds, each
      comprising 30 volumes with identical parameters (100 kV, 200 mAs, 0.5 sec
      rotation time). The duration of contrast material bolus (0.5 mL/kg of body
      weight) was 3.8 seconds in the first series (short bolus series) and 11.5 seconds
      in the second series (long bolus series), and the injection flow rate was adapted
      accordingly. In each pig, cortical kidney volume was determined by using the
      volume with the highest cortical enhancement. CT perfusion values were calculated
      for both series by using the maximum slope method and were statistically compared
      and correlated with the true perfusion values from the flow probe by using linear
      regression analysis. RESULTS: Mean true perfusion and CT perfusion values (in
      minutes(-1)) for the short bolus series were 1.95 and 2.03, respectively (P =
      .22), and for the long bolus series, they were 2.02 and 1.92, respectively (P =
      .12). CT perfusion showed very good correlation with true perfusion in both the
      short (slope, 1.01; 95% confidence interval: 0.91, 1.11) and long (slope, 0.92;
      95% confidence interval: 0.78, 1.04) series. On the basis of the regression
      analysis, CT perfusion values in the short bolus series were overestimated by 1%
      and those in the long bolus series were underestimated by 8%. CONCLUSION:
      Duration of contrast material bolus injection does not influence CT perfusion
      values substantially. The longer, clinically preferred intravenous injection
      scheme is sufficiently accurate for CT perfusion.

PMID- 24029649
TI  - Increased unenhanced bowel-wall attenuation at multidetector CT is highly
      specific of ischemia complicating small-bowel obstruction.
AB  - PURPOSE: To evaluate performance of increased bowel-wall attenuation on
      unenhanced 64-section multidetector computed tomographic (CT) images for
      diagnosing bowel-wall ischemia in patients with mechanical small-bowel
      obstruction (SBO) and to evaluate the diagnostic accuracy of multidetector CT in
      detecting small-bowel ischemia complicating SBO, with surgical and
      histopathologic findings as reference standard. MATERIALS AND METHODS: The local
      institutional review board approved this retrospective study; informed consent
      requirement was waived. In 44 patients (10 men, 34 women; age range, 30-100
      years) who were admitted because they were suspected of having SBO and treated
      surgically within the next 7 days, 45 multidetector CT scans were retrospectively
      reviewed. Two gastrointestinal radiologists performed independent blinded reviews
      of images to identify specific signs of ischemia; disagreements were resolved in
      consensus with a third gastrointestinal radiologist. Results were compared with
      both findings in prospective radiology reports and surgical and histopathologic
      findings. Fisher exact and chi(2) tests were used to assess associations between
      CT signs and ischemia, and the kappa statistic was used to assess interobserver
      agreement. RESULTS: In 19 of 45 (42%) multidetector CT scans, ischemia was
      confirmed at surgery and/or histopathologic examination. Increased bowel-wall
      attenuation on unenhanced images was significantly associated with ischemia (P <
      .0001); in this highly selected population, this sign had a 100% (24 of 24)
      specificity and a 56% (10 of 18) sensitivity. Sensitivity and specificity of
      multidetector CT for ischemia were 63% (12 of 19) and 92% (24 of 26),
      respectively, for the prospective reports and 84% (16 of 19) and 96% (25 of 26),
      respectively, for the consensus review. Decreased segmental bowel-wall
      enhancement was the most accurate 64-section multidetector CT sign for diagnosing
      ischemia (sensitivity, 78% [14 of 18]; specificity, 96% [24 of 25]; P < .0001).
      The small-bowel feces sign was significantly associated with ischemia (P =
      .0308). CONCLUSION: Increased bowel-wall attenuation on unenhanced 64-section
      multidetector CT images is a specific sign for ischemia complicating SBO.
      Diagnostic accuracy of 64-section multidetector CT for ischemia associated with
      SBO was excellent.

PMID- 24029650
TI  - Effect of weight and maturation on busulfan clearance in infants and small
      children undergoing hematopoietic cell transplantation.
AB  - Little information is currently available regarding the pharmacokinetics (PK) of
      busulfan in infants and small children to help guide decisions for safe and
      efficacious drug therapy. The objective of this study was to develop an algorithm
      for individualized dosing of i.v. busulfan in infants and children weighing <=12
      kg, that would achieve targeted exposure with the first dose of busulfan.
      Population PK modeling was conducted using intensive time-concentration data
      collected through the routine therapeutic drug monitoring of busulfan in 149
      patients from 8 centers. Busulfan PK was well described by a 1-compartment base
      model with linear elimination. The important clinical covariates affecting
      busulfan PK were actual body weight and age. Based on our model, the predicted
      clearance of busulfan increases approximately 1.7-fold between 6 weeks to 2 years
      of life. For infants age <5 months, the model-predicted doses (mg/kg) required to
      achieve a therapeutic concentration at steady state of 600-900 ng/mL (area under
      the curve range, 900-1350 MUM.min) were much lower compared with standard
      busulfan doses of 1.1 mg/kg. These results could help guide clinicians and inform
      better dosing decisions for busulfan in young infants and small children
      undergoing hematopoietic cell transplantation. 

PMID- 24029651
TI  - Temporal trends, clinical characteristics, and outcomes of histoplasmosis in a
      tertiary care center in Kentucky, 2000 to 2009.
AB  - The impact of highly active antiretroviral therapy (HAART) on the epidemiology of
      AIDS-associated histoplasmosis in the past decade is poorly defined. Among 100
      patients with histoplasmosis in an endemic region between 2000 and 2009, 42
      patients were immunocompetent, 32 were infected with HIV, and 26 were non-HIV
      immunocompromised patients. The percentage with HIV decreased 67% in 2000-2001 to
      18% in 2008-2009 (P = .004), while the proportion of non-HIV immunocompromised
      patients increased, 8% to 41% (P = .14). Histoplasma antigen was the most
      sensitive test (73%), whereas potassium hydroxide examination of clinical
      specimens was the least sensitive test (33%) in all 3 groups. Bronchoalveloar
      fluid culture (74%) had the highest yield among the cultures. The relapse rate
      was higher in HIV-infected patients compared to the other 2 groups (P = .04). The
      epidemiology of histoplasmosis in our endemic area has changed during the era of
      HAART. Organ transplantation and increasing use of immunosuppressive agents for
      chronic inflammatory conditions in non-HIV patients now account for most of the
      cases of histoplasmosis. 

PMID- 24029652
TI  - The role of radionuclide imaging in epilepsy, part 2: epilepsy syndromes.
AB  - PET and SPECT can play an important role in the evaluation of various epileptic
      syndromes, particularly those with unknown causes, by revealing various
      underlying abnormalities that may not be fully appreciated from MR imaging
      studies. In some cases, PET and SPECT provide crucial data that guide surgical
      resections of the epileptogenic zone for medically refractory epilepsy. In other
      cases, these neuroimaging modalities preclude a surgical option and can guide
      genetic studies. Longitudinal PET and SPECT studies may increase our
      understanding of the etiopathogenesis of epilepsy syndromes and provide a clearer
      picture of the natural history of neurologic progression. 

PMID- 24029653
TI  - The potential for low-dose functional studies in maternal-fetal medicine using
      PET/MR imaging.

PMID- 24029654
TI  - Reply: Prognostic implications of imaging-based bone marrow assessment in
      lymphoma: 18F-FDG PET, MR imaging, or 18F-FDG PET/MR imaging?

PMID- 24029655
TI  - Applying PET to broaden the diagnostic utility of the clinically validated CA19.9
      serum biomarker for oncology.
AB  - Despite their considerable advantages, many circulating biomarkers have well
      documented limitations. One prominent shortcoming in oncology is a high frequency
      of false-positive indications for malignant disease in upfront diagnosis. Because
      one common cause of false positivism is biomarker production from benign
      disorders in unrelated host tissues, we hypothesized that probing the sites of
      biomarker secretion with an imaging tool could be a broadly useful strategy to
      deconvolute the meaning of foreboding but inconclusive circulating biomarker
      levels. METHODS: In preparation to address this hypothesis clinically, we
      developed (89)Zr-5B1, a fully human, antibody-based radiotracer targeting tumor
      associated CA19.9 in the preclinical setting. RESULTS: (89)Zr-5B1 localized to
      multiple tumor models representing diseases with undetectable and
      supraphysiologic serum CA19.9 levels. Among these, (89)Zr-5B1 detected orthotopic
      models of pancreatic ductal adenocarcinoma, an elusive cancer for which the serum
      assay is measured in humans but with limited specificity in part because of the
      frequency of CA19.9 secretion from benign hepatic pathologies. CONCLUSION: In
      this report, a general strategy to supplement some of the shortcomings of
      otherwise highly useful circulating biomarkers with immunoPET is described. To
      expedite the clinical validation of this model, a human monoclonal antibody to
      CA19.9 (a highly visible but partially flawed serum biomarker for several
      cancers) was radiolabeled and evaluated, and the compelling preclinical evidence
      suggests that the radiotracer may enhance the fidelity of diagnosis and staging
      of pancreatic ductal adenocarcinoma, a notoriously occult cancer.

PMID- 24029656
TI  - 64Cu-DOTA-trastuzumab PET imaging in patients with HER2-positive breast cancer.
AB  - The purpose of this study was to determine the safety, distribution, internal
      dosimetry, and initial human epidermal growth factor receptor 2 (HER2)-positive
      tumor images of (64)Cu-DOTA-trastuzumab in humans. METHODS: PET was performed on
      6 patients with primary or metastatic HER2-positive breast cancer at 1, 24, and
      48 h after injection of approximately 130 MBq of the probe (64)Cu-DOTA
      trastuzumab. Radioactivity data were collected from the blood, urine, and normal
      tissue samples of these 6 patients, and the multiorgan biodistribution and
      internal dosimetry of the probe were evaluated. Safety data were collected for
      all the patients after the administration of (64)Cu-DOTA-trastuzumab and during
      the 1-wk follow-up period. RESULTS: According to our results, the best timing for
      the assessment of (64)Cu-DOTA-trastuzumab uptake by the tumor was 48 h after
      injection. Radiation exposure during (64)Cu-DOTA-trastuzumab PET was equivalent
      to that during conventional (18)F-FDG PET. The radioactivity in the blood was
      high, but uptake of (64)Cu-DOTA-trastuzumab in normal tissues was low. In 2
      patients, (64)Cu-DOTA-trastuzumab PET showed brain metastases, indicative of
      blood-brain barrier disruptions. In 3 patients, (64)Cu-DOTA-trastuzumab PET
      imaging also revealed primary breast tumors at the lesion sites initially
      identified by CT. CONCLUSION: The findings of this study indicated that (64)Cu
      DOTA-trastuzumab PET is feasible for the identification of HER2-positive lesions
      in patients with primary and metastatic breast cancer. The dosimetry and
      pharmacologic safety results were acceptable at the dose required for adequate
      PET imaging.

PMID- 24029657
TI  - Imaging VCAM-1 as an indicator of treatment efficacy in metastatic ovarian
      cancer.
AB  - The inability to successfully treat women with ovarian cancer is due in large
      part to the advanced stage of disease at diagnosis, the development of platinum
      resistance, and the lack of sensitive methods to monitor tumor progression and
      response to treatment. Vascular cell adhesion molecule-1 (VCAM-1) is expressed on
      the mesothelium of ovarian cancer patients. We investigated VCAM-1 expression as
      a marker of peritoneal metastasis and tumor response to platinum-based
      chemotherapy. METHODS: Peritoneal or omental biopsies obtained from women
      diagnosed with stage I, stage II, or stage III/IV ovarian cancer were evaluated
      by immunohistochemistry. The effects of carboplatin on mesothelial VCAM-1
      expression were determined in cultured cells by Western blot. Radiolabeled VCAM-1
      specific peptide imaging probes and SPECT were used in a mouse model of ovarian
      cancer peritoneal metastasis to identify VCAM-1 as a viable imaging target.
      RESULTS: VCAM-1 expression correlated with tumor stage. All specimens from stage
      I patients were negative, whereas 29% of stage II patients and 73% of stage
      III/IV patients were positive. Although most women with advanced stage disease
      expressed VCAM-1, the incidence of expression was reduced among women who
      received neoadjuvant chemotherapy, suggesting a role for chemotherapy in
      regulating VCAM-1 expression. Treatment of mesothelial cells in culture with
      carboplatin resulted in a transient decrease in VCAM-1 expression 4 h after
      treatment that returned to baseline within 16-24 h. In vivo imaging of VCAM-1
      also demonstrated an acute decrease in expression 4 h after carboplatin
      administration that recovered within 48 h in mice harboring platinum-resistant
      tumors. Chronic VCAM-1 expression reflected the effect of platinum-based
      treatment on tumor burden. Specifically, carboplatin treatment of mice with
      platinum-sensitive tumors showed reduced VCAM-1 expression, which correlated with
      reduced tumor burden; mice with platinum-resistant tumors retained elevated VCAM
      1 expression and tumor burden after treatment. CONCLUSION: Clinically relevant
      VCAM-1-specific imaging probes identify VCAM-1 expression as an indicator of
      ovarian cancer peritoneal metastasis and therapeutic response to platinum-based
      agents. These observations support testing the utility of VCAM-1 imaging probes
      to monitor treatment response in ovarian cancer patients, thus providing the
      potential to improve management of women with this disease.

PMID- 24029658
TI  - Circulating species of matrix Gla protein and the risk of vascular calcification
      in healthy women.

PMID- 24029659
TI  - Arterial elastance and its impact on intrinsic right ventricular function in
      palliated hypoplastic left heart syndrome.
AB  - BACKGROUND: Systemic right ventricular (RV) function is a major determinant of
      long-term outcome in patients with palliated hypoplastic left heart syndrome
      (HLHS). Abnormal elastic properties of the reconstructed aorta may negatively
      impact on ventricular function. We therefore aimed to assess arterial elastance
      and its relationship to systemic RV function in these patients. METHODS: Fifty
      six HLHS patients (median age 5.4 years; range 2.9-14.2 years) were studied at a
      median of 2.6 years (range 0.8-12.7 years) after completion of the Fontan
      circulation with the pressure-volume conductance system. RESULTS: Arterial
      elastance (Ea) was abnormally high and correlated inversely with RV ejection
      fraction (r=-0.42, P=0.001). However, end systolic elastance (Ees) - a load
      independent measure of intrinsic systolic ventricular function - and more so end
      diastolic stiffness (Eed) were positively correlated with Ea (Ees vs. Ea: r=0.44,
      P=0.001: Eed vs. Ea: r=0.62, P<0.0001). Patients who were treated for significant
      aortic arch obstruction after surgical palliation showed higher Ea and Eed even
      four years after successful treatment compared to the remainder of the group (Ea:
      3.4 +/- 1.2 vs. 2.8 +/- 1.0 mmHg/ml, P=0.04 and Eed: 0.67 +/- 0.44 vs. 0.45 +/-
      0.3 mmHg/ml, P=0.04). CONCLUSIONS: Arterial elastance is abnormally high in
      palliated HLHS patients and negatively impacts on ejection fraction but not on
      intrinsic systolic RV function early after completion of the Fontan circulation.
      Increased arterial elastance, however, is associated with increased RV diastolic
      stiffness with potential adverse effects on long-term outcome. Furthermore,
      arterial elastance and diastolic stiffness are particularly high in patients who
      needed treatment for aortic arch obstruction.

PMID- 24029660
TI  - Decreased serum brain-derived neurotrophic factor levels are correlated with
      exercise intolerance in patients with heart failure.

PMID- 24029661
TI  - Vascular endothelial growth factor blockade prevents the beneficial effects of
      beta-blocker therapy on cardiac function, angiogenesis, and remodeling in heart
      failure.
AB  - BACKGROUND: Impaired angiogenesis in the post-myocardial infarction heart
      contributes to the progression to heart failure. The inhibition of vascular
      endothelial growth factor (VEGF) signaling has been shown to be crucial for the
      transition from compensatory hypertrophy to cardiac failure. Importantly, beta
      adrenergic receptor blocker therapy has been also shown to improve myocardial
      perfusion by enhancing neoangiogenesis in the failing heart. METHODS AND RESULTS:
      Eight weeks from surgically induced myocardial infarction, heart failure rats
      were randomized to receive bisoprolol (B) or vehicle. At the end of a 10-week
      treatment period, echocardiography revealed reduced cardiac diameters and
      improved cardiac function in B-treated compared with vehicle-treated rats.
      Moreover, B treatment was associated with increased cardiac angiogenesis and in
      vivo coronary perfusion and reduced cardiac fibrosis. Importantly, 2 weeks after
      B treatment was started, increased cardiac VEGF expression and Akt and
      endothelial NO synthase activation were observed by comparing B-treated with drug
      untreated failing hearts. To test whether the proangiogenic effects of B act via
      activation of VEGF pathway, rats were intravenously injected with adenoviral
      vector encoding a decoy VEGF receptor (Ad-Flk) or a control adenovirus (Ad-C), at
      the start of the treatment with B. After 10 weeks, histological analysis revealed
      reduced capillary and coronary perfusion in B-treated plus Ad-Flk rats compared
      with B-treated plus Ad-C rats. Moreover, VEGF inhibition counteracted the
      positive effects of B on cardiac function and remodeling. CONCLUSIONS: beta
      Blockade promotes cardiac angiogenesis in heart failure via activation of VEGF
      signaling pathway. beta-Blocker-induced enhancement of cardiac angiogenesis is
      essential for the favorable effects of this therapy on cardiac function and
      remodeling.

PMID- 24029662
TI  - Human leukocyte antigen B distribution in HIV discordant cohort from India.
AB  - Limited reports are available on association of HLA-B with HIV infection from
      India, a home to the third largest population of HIV infected people in the
      world. This emphasizes the need to have more information specifically the genetic
      constitution of HIV serodiscordant couples (DCs), where one spouse is
      seropositive (HSP) while the other remains seronegative (HSN) even after repeated
      exposure. Hence, aim of this study was to document association of HLA-B with HIV
      infection in DCs living in Mumbai, India. A cohort was designed to enroll DCs
      attending the ICTC/Shakti Clinic of KEM Hospital, Mumbai. A group of unexposed
      volunteers were also enrolled as healthy controls (HC). HLA-B alleles were typed
      using sequence-specific oligonucleotide probes. Allele frequency comparison was
      done using 2*2 contingency tables. Results were considered significant, when
      p<0.05 with two-tailed Fisher's exact test. At HLA-B locus, the frequencies of
      HLA-B*40;-B*35;-B*07;-B*15;-B*51;-B*44;-B*52;-B*37 and -B*57 were found in
      decreasing order in the population. Frequency of HLA-B*35 allele was
      significantly higher (HSP vs HSN; p<0.02 and HSP vs HC; p<0.04) in HSP. HLA-B*40
      (HSN vs HSP; p<0.01 and HC vs HSP; p<0.01) and HLA-B*18 (HSN vs HSP; p<0.02) were
      significantly associated with HSN. Both HSN and HC had similar HLA-B*35 and -B*40
      allele frequency. HLA-B*57 allele was observed in 15 individuals (3.69%).
      However, HLA-B*57:01 which is known to be associated with adverse reactions
      against Abacavir was observed in 7 of them. HLA-B*39 was observed exclusively in
      HSP. Our observation in DCs confirmed the association of HLA-B*35 with
      susceptibility while HLA-B*40 (specifically *B40:06), -B*18 with protection.
      These identified alleles can be used as possible marker associated with HIV
      transmission. In India, HLA screening is not carried out before initiation of HIV
      treatment. However, the presence of HLA-B*57:01 in the population emphasizes the
      importance of such screening to predict/avoid Abacavir hypersensitivity. 

PMID- 24029663
TI  - Reversible expression of CD138 on mature follicular B cells is downregulated by
      IL-4.
AB  - CD138, known as a marker of plasma cells, was reported to be expressed to an
      intermediate level in the murine bone marrow precursor B cells. Here an
      intermediate level of CD138 expression was also noted in a subpopulation of
      splenic follicular B cells, which were distinguishable from CD138(high) plasma
      cells, whereas the majority of transitional or marginal zone B cells did not
      express CD138. These CD138(int) B cells were IgM(low)IgD(high) mature B cells,
      located within follicular B cell zone, and expressed a lower level of CD21 than
      CD138(-) follicular B cells. During in vitro culture of splenic cells, the
      proportion of CD138(int) B cells increased, which was noticeably reversed by the
      addition of IL-4 to the culture. The experiments with sorted CD138(int) cells
      showed that IL-4-mediated regulation of the CD138 expression was B cell-intrinsic
      and independent of in vitro B cell death. Our results demonstrate that mouse
      CD138(int) B cells characterize a subpopulation of IgM(low)IgD(high) mature
      follicular B cells. The CD138 expression on follicular B cells may represent a
      reversible status, reflecting a dynamic state probably influenced by IL-4. 

PMID- 24029664
TI  - Supraglottic laryngeal tumor microenvironmental factors facilitate STAT3
      dependent pro-tumorigenic switch in tumor associated macrophages to render utmost
      immune evasion.
AB  - Content of tumor microenvironment (TME) is varied greatly among different types
      of laryngeal tumors, namely, supraglottic, glottic and subglottic tumors. These
      three different TMEs shape infiltrating monocytes/macrophages toward M2 genotypes
      in variable degrees. Results obtained from in vitro studies demonstrated extent
      of expression of M2 phenotypic features on macrophages was maximum after their
      exposure to supraglottic laryngeal tumor cell lysates (SLTCL) than glottic or
      subglottic lysates. Moreover, M2 macrophages generated under influence of SLTCL
      show less nitric oxide production, greater IL-10: IL-12 ratio and poor antigen
      presentation. Co-culture of such M2 macrophages with T cells from healthy donors
      resulted decreased activation of T cells and T cell mediated tumor cell
      cytotoxicity, than, glottic or subglottic. SLTCL mediated macrophage polarization
      is STAT3 dependent and might be one of the major factors for severe immune
      paralysis leading to poor prognosis of supraglottic laryngeal tumor bearer
      following standard treatment. 

PMID- 24029666
TI  - Disease-related surgery in patients with distant metastatic breast cancer.
AB  - INTRODUCTION: This study evaluates the frequency of and indications for disease
      related surgical procedures in the palliative breast cancer (BC) situation.
      PATIENTS & METHODS: Based on a cohort of women who were treated for newly
      diagnosed BC during a 20-year period (1990-2009), we analyzed 340 patients who
      developed distant metastatic disease (DMD) until 2011 and died (i.e. still
      ongoing palliative disease courses were not included). RESULTS: One hundred and
      twenty-seven surgical procedures were performed in 100 patients (29.4% of all
      patients with metastatic disease). The most common site for surgery was breast (n
      = 60, 47.2%). The primary tumor was removed at first diagnosis of DMD in 43
      patients (33.9%); sixteen operations (12.6%) were performed for local recurrence.
      In 37 patients, 50 surgical procedures (39.4%) were necessary to stabilize
      osseous structures due to metastases. Procedures were rarely performed on other
      common metastatic sites: lung: n = 1 (0.8%); liver: n = 1 (0.8%), brain: n = 4
      (3.1%). When excluding surgery for primary breast tumors at initial diagnosis of
      DMD from analysis, 34 of 84 surgeries (40.4%) were performed in the first third
      of survival follow-up (i.e. period of metastatic disease survival); operations in
      the last two-thirds each totaled 29.8% (n = 25). The median survival after
      surgery was 16 months (range: 0.5-89 months). CONCLUSIONS: In a cohort of BC
      patients who had primary or developed secondary DMD, nearly one third of the
      patients received disease-related surgical procedures during their palliative
      disease course. This high rate of operations shows that surgery has a clearly
      established role in the palliative therapy concept.

PMID- 24029667
TI  - Post-traumatic stress disorder in patients 3 years after aneurysmal subarachnoid
      haemorrhage.
AB  - BACKGROUND: Subarachnoid haemorrhage (SAH) from a ruptured intracranial aneurysm
      accounts for approximately 5% of all strokes. Post-traumatic stress disorder
      (PTSD) is common in the early phase after recovery from aneurysmal SAH. The aim
      of our study was to examine the prevalence of PTSD 3 years after SAH, its
      predictors, and relationship with health-related quality of life (HRQoL) in
      patients living independently in the community. METHODS: From a prospectively
      collected cohort of 143 patients with aneurysmal SAH who visited our outpatient
      clinic 3 months after SAH, 94 patients (65.7%) completed a mailed questionnaire 3
      years after SAH. We assessed PTSD with the Impact of Event Scale and HRQoL with
      the Stroke-Specific Quality of Life Scale (SS-QoL). The chi(2) and t tests were
      used to investigate if patients who returned the questionnaires were different
      from those who did not reply. Non-parametric tests (chi(2) and Mann-Whitney
      tests) were used to test for differences between patients with and without PTSD.
      Relative risks and 95% confidence intervals were calculated. RESULTS: No relevant
      differences in demographic (age, sex, education) or SAH characteristics (clinical
      condition on admission, complication, location of aneurysm, Glasgow Outcome Scale
      score at 3 months) were seen between participants and drop-outs. In 24 patients
      (26%), Impact of Event Scale scores indicated PTSD. Passive coping style
      (relative risk, 5.7; 95% confidence interval, 2.1-15.3), but none of the
      demographic or SAH-related factors, predicted PTSD. The mean SS-QoL total score
      was 4.2 (SD 1.1), indicative of a relatively satisfactory HRQoL. PTSD was
      associated with lower HRQoL (p < 0.001), a mean SS-QoL score of 4.4 (SD 1.0)
      without PTSD, and a mean SS-QoL score of 3.5 (SD 1.1) with PTSD. CONCLUSIONS:
      Even 3 years after SAH, 1 out of 4 patients had PTSD, which was associated with
      reduced HRQoL. Passive coping style was the most important predictor. There is a
      need to organize SAH care with more attention to and treatment of PTSD.
      Strategies shown to reduce PTSD in other conditions should be tested for
      effectiveness in SAH patients.

PMID- 24029665
TI  - Significant association of TNFalpha and IL-6 gene with male infertility--an
      explorative study in Indian populations of Uttar Pradesh.
AB  - In this study were aimed to identify the association of SNPs candidate genes of
      TNF-alpha and IL-6 with hormones levels and sperm cells death in infertile
      subjects of Uttar Pradesh population in North India. The study population
      comprised, fertile donor (control group) and infertile group patients i.e.
      normozoospermic (idiopathic unexplained), oligozoospermic and asthenozoospermic
      groups, with 260 subjects in each group. Subjects were selected from the
      Departments of Urology, K.G's Medical University and Urology, SGPGIMS, Lucknow,
      India. The allele-specific polymerase chain reaction (PCR) and PCR-RFLP were used
      to investigate the substitution of the guanine (G)-to-adenosine (A) at position
      308 and guanine (G)-to-cytosine (C) at position-174 in the promoter regions of
      the TNF-alpha and IL-6 genes, respectively. Further their relation to male
      fertility and sperm function were also investigated. It was found that the
      substitution levels from G to A and from G to C in the TNF-alpha and IL-6 genes,
      respectively, were significantly higher in the infertile subjects as compared to
      that of control group. The apoptosis and necrosis levels were also higher in
      oligozoospermic and asthenozoospermic infertile subjects. Further it was found to
      be associated with increased level of reactive oxygen species as observed in
      oligozoospermic and asthenozoospermic subjects. However, a significant decrease
      in testosterone and luteinizing hormone with increased prolactin and follicle
      stimulating hormones was observed in infertile subjects. The study populations
      indicating a strong association between TNF-alpha G-308A and IL-6 G-174C
      substitution with infertile men which is further supported by allele and genotype
      meta-analysis and thus established it as a risk factor. 

PMID- 24029668
TI  - Why children are not vaccinated: a review of the grey literature.
AB  - In collaboration with WHO, IMMUNIZATION basics analyzed 126 documents from the
      global grey literature to identify reasons why eligible children had incomplete
      or no vaccinations. The main reasons for under-vaccination were related to
      immunization services and to parental knowledge and attitudes. The most
      frequently cited factors were: access to services, health staff attitudes and
      practices, reliability of services, false contraindications, parents' practical
      knowledge of vaccination, fear of side effects, conflicting priorities and
      parental beliefs. Some family demographic characteristics were strong, but
      underlying, risk factors for under-vaccination. Studies must be well designed to
      capture a complete picture of the simultaneous causes of under-vaccination and to
      avoid biased results. Although the grey literature contains studies of varying
      quality, it includes many well-designed studies. Every immunization program
      should strive to provide quality services that are accessible, convenient,
      reliable, friendly, affordable and acceptable, and should solicit feedback from
      families and community leaders. Every program should monitor missed and under
      vaccinated children and assess and address the causes. Although global reviews,
      such as this one, can play a useful role in identifying key questions for local
      study, local enquiry and follow-up remain essential.

PMID- 24029669
TI  - Treatment outcomes in a cohort of patients with chronic hepatitis B and human
      immunodeficiency virus co-infection in Mumbai, India.
AB  - Treatment experiences with patients co-infected with human immunodeficiency virus
      (HIV) and hepatitis B virus (HBV) in resource-limited settings remain poorly
      documented. This study aimed to evaluate the treatment outcomes in a cohort of
      HIV/HBV co-infected individuals receiving tenofovir/lamivudine (TDF/3TC)-based
      antiretroviral therapy (ART) in a programmatic setting in Mumbai, India.
      Additionally, a cross-sectional laboratory study was carried out measuring
      serologic and virologic parameters. A total of 57 patients who received TDF/3TC
      were included in the study. Of these, 52 (91%) were male and the mean age was
      38.7 years. The median follow-up period was 16.8 months (IQR:7.9-37.9). Forty
      three patients were included in the cross-sectional laboratory study, of whom 38
      (67%) were HBeAg(+) positive. Four patients had serum HBsAg conversion to
      negative and had developed anti-HBs-antibodies. HBV-DNA became undetectable (<1.3
      log10 copies/ml or <20 IU/ml) in 35.5% and 75% of the HBeAg(+) and HBeAg(-)
      patients, respectively. Overall, 46.5% of patients had undetectable HBV-DNA and
      90.7% had adequately suppressed HBV-DNA (<3.3 log10 copies/ml or <2000 IU/ml).
      The median reduction in serum HBV-DNA was 6 log10 copies/ml. In 29 patients (63%)
      HIV viral load was undetectable. Outcomes included seven (12%) deaths, four (7%)
      lost to follow-up, one (2%) transferred out and 45 (79%) alive and on treatment.
      In conclusion, good treatment outcomes were achieved in a cohort of HIV/HBV co
      infected patients in India. In regions with a high HIV/HBV burden, all HIV
      infected individuals should be tested for chronic hepatitis B. A TDF/3TC-backbone
      could be considered as first-line standardized ART regimen in these settings.

PMID- 24029670
TI  - The burden of hypertension and its risk factors in Malawi: nationwide population
      based STEPS survey.
AB  - Hypertension is the most common cause of cardiovascular diseases, accounting for
      at least half of haemorrhagic and ischaemic strokes, heart failure and renal
      failure in sub-Saharan Africa. However, population-based data to inform policies
      are scarce. Using the WHO STEPwise approach to chronic disease risk factor
      surveillance, a population-based nationwide survey was conducted on participants
      aged 25-64 years in Malawi. Detailed findings on the burden of hypertension are
      presented in this paper. Blood pressure (BP) was measured in 3727 participants.
      The age-standardised prevalence of hypertension (BP >=140/90 mmHg) was 33.2% (95%
      CI 30.9-35.6%). Hypertension was more frequent in males than females (36.9% vs
      29.9%), alcohol drinkers than non-drinkers (40.9% vs 31.6%), overweight than non
      overweight (41.5% vs 30.7%) and increased with increasing age (21.4% in 25-34
      years old vs 59.2% in 55-64 years old). Three-quarters of the participants said
      they never had their BP measured before and 94.9% of those with hypertension said
      they were not aware that they had such a medical problem. High prevalence of
      hypertension and its risk factors calls 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- 24029671
TI  - Four years of experience with antiretroviral therapy in adult patients in
      Karachi, Sindh, Pakistan.
AB  - The Sindh AIDS Control Program (SACP) in Pakistan began dispensing combination
      antiretroviral therapy (ART) in May 2006 in Karachi. This study aimed to assess
      the management and outcomes of ART-treated patients. Data were extracted from
      medical records of adult patients registered with the SACP who received ART
      between May 2006 and May 2010. In total, 300 patients received ART, of whom 77.7%
      were men. The median CD4 cell count at the time of joining the SACP was 130
      cells/mm(3). ART was nevirapine-based in 69.1% of cases and was correctly
      prescribed in 97.3%. Of 257 patients who received >=1 month of ART, >90% were
      regular with their medications and appointments. Of the 300 patients, 70 (23.3%)
      had HIV-related deaths and 4 (1.3%) had non-HIV-related deaths, whereas 32
      (10.7%) transferred out and 16 (5.3%) stopped attending the clinic and could not
      be traced. Estimated survival in the first 6 months stratified by initial CD4
      lymphocyte count >=50 cells/mm(3) and <50 cells/mm(3) was 85.8% (95% CI 80.8
      90.0%) and 52.2% (95% CI 40.9-63.1%), respectively. Viral suppression was
      achieved in 95.4% of those who survived beyond 3 months of starting ART. ART can
      be managed adequately with excellent patient adherence and satisfactory clinical
      outcomes in a resource-limited setting.

PMID- 24029672
TI  - Patient referral patterns by family doctors and to selected specialists in
      Tajikistan.
AB  - Referral rates are a key measure for the functioning of a healthcare system. The
      objective of this study was to assess referral patterns from family doctors (FD)
      and selected specialists to other specialists and hospitals in two rayons
      (districts) of Tajikistan. Quantitative data on referral decisions and self
      referral was collected among FDs and selected specialists over a 10-workday
      period in 2008. For comparison, the collected information was contrasted to
      routinely recorded data and figures from the national health information system
      (HIS). The mean referral rate of FDs was 20.0% while the referral rate according
      to the HIS was 4.5%. In one rayon, the majority of the referred patients were
      sent to hospitals (65.6%) while in the other rayon, 65.9% were advised to see a
      specialist. Technical diagnostic tests not available at the primary healthcare
      level triggered the majority of all referrals. A need for diagnosis and treatment
      by specialists accounted for 19.2% of the referrals. Self-referral was common
      among patients seen by ophthalmologists and otorhinolaryngologists (76.0%). We
      conclude that referral rates among Tajik FD patients are high and self-referral
      of patients to a specialist is the norm. The routine HIS fails to provide
      accurate data.

PMID- 24029673
TI  - Impact of a customized peer-facilitators training program related to sexual
      health intervention.
AB  - This study aimed to develop and implement a customized training program related
      to the delivery of an integrated human immunodeficiency virus - sexually
      transmitted infections (HIV-STI) risk reduction intervention for peer
      facilitators and to evaluate its immediate outcome including changes in trainee
      knowledge, attitudes, and self-reported competence and confidence. We developed
      and delivered a structured training program and materials about HIV and STI
      prevention in a university setting. The training was offered to candidate
      facilitators who were planned to be involved in a larger project, known as
      Integrated HIV-STI Risk Reduction Program. Ten candidate facilitators
      participated in the training program and completed both the pretest and posttest
      survey questionnaire. The data were analyzed using SPSS version 17.0 software
      package and Wilcoxon signed rank test was applied to assess the impact of the
      training program. Overall, the trainees' performance in HIV-related and STI
      knowledge, attitude and stigma scores had significantly increased compared to the
      baseline. The median scores for HIV and STI knowledge after the training
      significantly increased from 22.0 to 30.5 (p=0.007) and 8.0 to 9.5 (p=0.005),
      respectively, whereas the median score on the positive attitude towards HIV and
      STI prevention rose from 39.0 to 57.0 (p=0.011). Upon completion of the program,
      80-100% of the trainees believed that they were competent and confident in
      performing most of the designed sexual health intervention activities. This
      preliminary study suggests that a customized on-site training program on sexual
      health intervention could significantly improve their knowledge, attitude and
      practice related to HIV-STI prevention.

PMID- 24029674
TI  - Fee or free? Trading equity for quality of care for primary health care in Papua
      New Guinea.
AB  - Fee charging is common at primary health facilities in Papua New Guinea (PNG) and
      is poorly regulated. To understand the extent of user fees and their implications
      on access and service delivery, structured interviews with staff and users at 44
      primary health facilities were conducted across seven provinces of PNG.
      Facilities were stratified by management (government or non-government) and
      accessibility (easy or difficult) and were then randomly selected. Staff at 37
      (84%) of the 44 facilities reported charging user fees for at least some goods
      and services both at church- and government-run facilities. Twenty-one percent of
      all exit survey respondents said user fees had prevented them attending a health
      facility on at least one occasion. Almost one-third of facilities were in
      contradiction of national health policies, charging for deliveries and domestic
      violence injuries. Moreover, 33 of the 37 facilities charging user fees reported
      that revenue raised was used to cover operational costs of running health
      facilities meant to be funded by other sources. Whilst fee revenue reportedly
      provided valuable additional funding to increase capacity for service delivery,
      fees caused a barrier to access for some and exemptions were inconsistently
      applied, often in contradiction with national health policy.

PMID- 24029675
TI  - Pre-hospital care seeking behaviour for childhood acute respiratory infections in
      south-western Nigeria.
AB  - WHO/UNICEF currently recommend that childhood malaria and pneumonia be managed
      together in the community; most African countries are in the process of
      developing this policy. We conducted a cross-sectional study to determine
      maternal awareness of general danger signs of childhood illnesses and the
      prevalence, determinants and sources of pre-hospital treatment by mothers during
      their child's acute respiratory illness in a poor urban community in south
      western Nigeria. A total of 226 mothers were interviewed. Only 4.9% of the
      mothers were aware of the two pneumonia symptoms: difficult breathing and fast
      breathing. About 75% of the children were given pre-hospital medication at home
      and only 16.5% of them received the drugs within 24 hour of symptom recognition.
      Drug shops/patent medicine vendors (PMVs; 70.6%) were the most common source of
      care. Wishing to try home management first (46.6%); waiting for the child to
      improve (14.4%) and lack of money (31.6%) delayed care-seeking. Older maternal
      age (aOR 2.3; 95% CI 1.2-4.4) and having a child with cough and difficult and/or
      fast breathing (aOR 2.3; 95% CI 1.1-5.2) were positive predictors of pre-hospital
      treatment. Maternal education and adequately equipping PMVs could improve prompt
      access to integrated community-based child health services in Nigeria.

PMID- 24029676
TI  - Injection safety assessments in two Chinese provinces, 2001-2009: progress and
      remaining challenges.
AB  - In 2009, an assessment of injection practices in Fumeng County (Liaoning
      Province) and Wulong County (Chongqing Municipality) (random sample of 29
      hospitals, 40 village clinics and 400 villagers) was conducted and the results
      were compared with a prior 2001 assessment (same area, same WHO assessment tool).
      In 2009, all facilities in Fumeng and Wulong used new, disposable syringes
      compared with 34% in both counties in 2001. Moreover, 59% (95% CI 37-80%) and 74%
      (95% CI 55-94%) of providers in Fumeng and Wulong, respectively, collected used
      sharps safely compared with 33% (95% CI 20-45%) and 36% (95% CI 20-53%) in 2001.
      In Fumeng and Wulong, respectively, 5% (95% CI 0-15%) and 50% (95% CI 25-76%) of
      facilities discarded injection devices in the regular trash compared with 7% (95%
      CI 2-12%) and 64% (95% CI 47-80%) in 2001. Between 2001 and 2009, the annual
      average number of injections per person increased from 1.8 to 6.3 (95% CI 4.5
      8.1) in Fumeng and was stable [3.4 and 3.1 (95% CI 1.9-4.3)] in Wulong. Overall,
      between 2001 and 2009, sterilisable injection devices disappeared and disposal
      practices improved. However, unsafe practices persisted, which should be
      improved. Use of injections to administer medications may be increasing and must
      be reduced.

PMID- 24029677
TI  - Is the existing knowledge and skills of health workers regarding eye care in
      children sufficient to meet needs?
AB  - Although uncommon, childhood blindness is a major contributor to blind-person
      years in Africa. Children with vision-related problems need urgent referral, but
      existing evidence suggests that there is delay in presentation. A pilot study in
      a random selection of government dispensaries in two districts of Kilimanjaro
      Region, Tanzania, was conducted to assess the knowledge and skills of primary
      healthcare workers regarding eye care needs of children. Questionnaires were
      administered to 16 healthcare workers, and in-depth interviews were conducted
      with 9 health workers and 2 key informants. Overall, 88% of workers recognised
      cataract in a picture, 63% knew that it required surgery but only 50% realised
      surgery was urgent. Only 38% recognised squint as needing referral and none
      considered this urgent. Moreover, 38% could correctly suggest a cause of a large
      corneal scar and 44% of workers believed that children with albinism need to
      attend schools for the blind. Poor knowledge of referral and treatment guidelines
      are likely due to a number of factors, including inadequate training and the
      rarity of childhood blindness. Primary eye care manuals should be reviewed to
      ensure that information regarding childhood blindness is adequate and
      appropriate. Referral pathways should also be revised.

PMID- 24029678
TI  - Considerations in the selection of healthcare providers for mothers and children
      in Bo, Sierra Leone: reputation, cost and location.
AB  - The factors that influence the selection of a healthcare provider once the
      decision to seek care has been made can be summarized using a triad of cost,
      location and reputation. The goal of this study was to identify which of these
      factors is the primary consideration when women in urban Bo, Sierra Leone, select
      a healthcare provider for themselves or their children. We interviewed 1091
      mothers during a household census of two neighbourhoods of Bo in April 2010.
      Reputation was the top consideration for about half of the women, cost was the
      second most common priority, and the location of the healthcare facility was the
      primary consideration for less than 7% of the participants. The majority of women
      said they would select a new provider if cost was not a barrier. Socioeconomic
      characteristics were not significant predictors of whether cost, location or
      reputation was selected as the highest-ranked consideration. This evidence for
      the importance of reputation in healthcare decision-making even in low-resource
      areas highlights the need for health systems to address issues of quality and
      responsiveness, and not just cost, in order to increase access to and utilization
      of health services.

PMID- 24029679
TI  - Health-seeking behaviour for febrile illness in malaria-endemic Kolasib district,
      Mizoram, India.
AB  - Early diagnosis and complete treatment (EDCT) is an important strategy for
      malaria control in India's National Vector Borne Disease Control Programme. The
      success of this strategy is closely linked to people's health-seeking behaviour.
      A study was conducted to determine the treatment-seeking behaviour of suspected
      malaria patients in Kolasib, a highly malaria-endemic district in Mizoram, India.
      Approximately one-third of the 540 fever patients interviewed sought initial
      treatment from public health facilities, whilst the majority either took self
      treatment or purchased medicines from private pharmacies. Approximately 20% of
      patients sought treatment after 48 h of fever onset. Patients aged >14 years and
      those who had an income >=Rs 5000 (US$104) were more likely to receive treatment
      from non-governmental health facilities. Patients aged >14 years and those
      residing in difficult locations were more likely to take treatment after 48 h of
      fever. To improve implementation of the EDCT strategy, it is necessary to conduct
      health education campaigns in the district (i) about seeking early treatment from
      public health facilities, including the fever treatment depots established in all
      villages, and (ii) discouraging the practice of self-treatment.

PMID- 24029680
TI  - What proportion of patients diagnosed with TB and started on treatment in
      Manicaland Province, Zimbabwe, are registered?
AB  - A retrospective record review was carried out in selected districts in Manicaland
      Province, Zimbabwe, to compare the number of patients diagnosed and started on
      anti-TB treatment with the number listed in the TB register. There were 574
      patients (290 females) diagnosed and treated for TB during the first 6 months of
      2010, of whom 248 (43%) were not registered. Not being registered was associated
      with attending a rural hospital. An unacceptably high proportion of patients
      diagnosed and treated for TB were not being registered and were therefore not
      reported to national authorities or the WHO. The registration process in Zimbabwe
      requires review.

PMID- 24029681
TI  - The return of unexpected research results in a biobank study and referral to
      health care for heritable long QT syndrome.
AB  - BACKGROUND: In this study, we examined how biobank study participants, who were
      found to have long QT syndrome (LQTS), a potentially life-threatening but
      treatable cardiac arrhythmia condition, experienced the process of disclosure of
      unexpected results and referral to health care. METHODS: All 27 subjects with a
      LQTS mutation finding were asked to complete a questionnaire. Four participants
      did not uptake the re-testing and 5 others did not respond to the questionnaire.
      We received 17 questionnaires from 6 males and 11 females, aged 46-82; 5 of them
      were also willing to participate in qualitative interviews. RESULTS: Of the
      respondents, 16/17 had experienced the process of receiving the results as
      positive and useful, especially if they had had symptoms. One respondent
      experienced the process negatively due to concerns related to informing her
      children. All respondents felt that genetic results should be reported back to
      the participants, while 2 indicated that this should occur only in the case of
      treatable conditions. Respondents had informed all of their children about the
      genetic condition, except 2 minors. CONCLUSIONS: The respondents from a
      population biobank study who were informed about an unexpected genetic finding
      evaluated this process as mainly positive. They considered that delivering
      genetic information about a life-threatening but actionable condition has more
      beneficial than adverse consequences. The feedback policy for biobanks should
      include how and who is informed, advise treatment or care pathways for actionable
      findings, and it should also include suitable options for those who do not want
      to know about such findings.

PMID- 24029683
TI  - Driving factors of influenza transmission in the Netherlands.
AB  - Influenza epidemics in temperate regions show a characteristic seasonal pattern
      with peak incidence occurring in winter. Previous research has shown that low
      absolute humidity and school holidays can both affect influenza transmission.
      During an epidemic, transmission is strongly influenced by the depletion of
      susceptibles (i.e., increase in the number of those immune). To assess how much
      variability in influenza transmission intensity is due to each of these driving
      factors, we used a long time series of the number of weekly visits to general
      practitioners for influenzalike illness in the Netherlands from 1970-2011 and
      transformed this into a time series of weekly influenza reproduction numbers,
      which are a measure of transmission intensity. We used statistical regression
      techniques to quantify how the reproduction numbers were affected by each driving
      factor. We found a clear ranking of importance of driving factors in explaining
      the variation in transmission intensity. Most of the variation (30%) was
      explained by the depletion of susceptibles during the season, 27% was explained
      by between-season effects, and 3% was explained by absolute humidity. School
      holidays at the Christmas period did not have a statistically significant effect
      on influenza transmission. Although the influence of absolute humidity was small,
      its seasonal fluctuations may determine when sustained influenza transmission is
      possible and may thus drive influenza seasonality.

PMID- 24029682
TI  - Noise propagation in resolution modeled PET imaging and its impact on
      detectability.
AB  - Positron emission tomography imaging is affected by a number of resolution
      degrading phenomena, including positron range, photon non-collinearity and inter
      crystal blurring. An approach to this issue is to model some or all of these
      effects within the image reconstruction task, referred to as resolution modeling
      (RM). This approach is commonly observed to yield images of higher resolution and
      subsequently contrast, and can be thought of as improving the modulation transfer
      function. Nonetheless, RM can substantially alter the noise distribution. In this
      work, we utilize noise propagation models in order to accurately characterize the
      noise texture of reconstructed images in the presence of RM. Furthermore we
      consider the task of lesion or defect detection, which is highly determined by
      the noise distribution as quantified using the noise power spectrum. Ultimately,
      we use this framework to demonstrate why conventional trade-off analyses (e.g.
      contrast versus noise, using simplistic noise metrics) do not provide a complete
      picture of the impact of RM and that improved performance of RM according to such
      analyses does not necessarily translate to the superiority of RM in detection
      task performance. 

PMID- 24029684
TI  - Is obesity associated with a decline in intelligence quotient during the first
      half of the life course?
AB  - Cross-sectional studies have found that obesity is associated with low
      intellectual ability and neuroimaging abnormalities in adolescence and adulthood.
      Some have interpreted these associations to suggest that obesity causes
      intellectual decline in the first half of the life course. We analyzed data from
      a prospective longitudinal study to test whether becoming obese was associated
      with intellectual decline from childhood to midlife. We used data from the
      ongoing Dunedin Multidisciplinary Health and Development Study, a population
      representative birth cohort study of 1,037 children in New Zealand who were
      followed prospectively from birth (1972-1973) through their fourth decade of life
      with a 95% retention rate. Intelligence quotient (IQ) was measured in childhood
      and adulthood. Anthropometric measurements were taken at birth and at 12
      subsequent in-person assessments. As expected, cohort members who became obese
      had lower adulthood IQ scores. However, obese cohort members exhibited no excess
      decline in IQ. Instead, these cohort members had lower IQ scores since childhood.
      This pattern remained consistent when we accounted for children's birth weights
      and growth during the first years of life, as well as for childhood-onset
      obesity. Lower IQ scores among children who later developed obesity were present
      as early as 3 years of age. We observed no evidence that obesity contributed to a
      decline in IQ, even among obese individuals who displayed evidence of the
      metabolic syndrome and/or elevated systemic inflammation.

PMID- 24029685
TI  - Molecular epidemiology of norovirus infections in symptomatic and asymptomatic
      children from Bobo Dioulasso, Burkina Faso.
AB  - BACKGROUND: Noroviruses (NoV) are a leading cause of gastroenteritis worldwide.
      Few epidemiological data regarding the NoV strains circulating in African
      countries are available. OBJECTIVES: To determine the prevalence of NoV in Bobo
      Dioulasso (Burkina Faso) in both symptomatic and asymptomatic gastroenteritis
      patients. STUDY DESIGN: Patients both with and without gastro-intestinal
      disorders were selected. Clinical and epidemiological data, as well as stool
      samples, were collected through March to April 2011. NoV molecular detection
      (genogrouping and genotyping) and viral load quantification were also performed
      for all samples. RESULTS: NoV were detected in 22.2% of the 418 collected stool
      samples (21.2% and 24.8% from the 293 symptomatic patients (SP) and the 125
      asymptomatic patients (ASP) respectively). Genogroup (G) distribution was 7.5%,
      10.2% and 3.4% for GI, GII and both GI/GII respectively among SP and 12.0%, 11.2%
      and 1.6% for GI, GII and both GI/GII, respectively, among ASP. Average viral load
      values were higher in SP than in ASP for GI (p = 0.03) but not for GII.
      Phylogenic analysis showed a high degree of genotype diversity in SP and ASP. One
      recombinant GII.7/GII.6 sequence was, to the best of our knowledge, detected for
      the first time. CONCLUSIONS: This study enabled identification of the specific
      molecular epidemiology of NoV strains circulating in a representative country in
      Eastern Africa, and additionally showed that ASP could play an important
      "reservoir" role. A high strain diversity was detected with a surprisingly high
      proportion of NoV GI compared to the common genotypes usually reported in
      comparable epidemiological studies.

PMID- 24029686
TI  - Performance of an alternative HIV diagnostic algorithm using the ARCHITECT HIV
      Ag/Ab Combo assay and potential utility of sample-to-cutoff ratio to discriminate
      primary from established infection.
AB  - BACKGROUND: The ARCHITECT HIV Ag/Ab Combo assay has a wide dynamic range for
      determining the sample-to-cutoff ratio (S/CO) values compared to other diagnostic
      HIV antibody assays. OBJECTIVES: Determine the performance of an HIV testing
      algorithm that uses the ARCHITECT combo assay in the clinical setting and explore
      the utility of the signal-to-cutoff (S/CO) ratio to predict acute HIV-1 infection
      status. STUDY DESIGN: A retrospective analysis of clinical samples from a
      hospital and referral population screened for HIV-1 infection between May 2011
      and March 2013. Repeatedly reactive samples were tested using the Multispot HIV
      1/HIV-2 rapid test and depending on that result, confirmatory orthogonal testing
      used the Western blot (WB) for HIV-1, Immunoblot for HIV-2 and nucleic acid
      amplification testing (NAAT) for HIV RNA. RESULTS: A total of 21,317 test results
      were evaluated of which 509 were ARCHITECT repeatedly reactive; of these, 422
      were Multispot-reactive only for HIV-1 (413 WB-positive; 9 indeterminate), 4 were
      Multispot-reactive for both HIV-1 and HIV-2 (one HIV-2 immunoblot-positive with
      17 HIV-2 RNA copies/mL) and 83 were Multispot-non-reactive of which 15 were HIV-1
      RNA positive and represented acute HIV-1 infection. There was an association
      among the ARCHITECT S/CO (median; IQR) values for antibody-negative (0.14; 0.11
      0.16), acute infection (33; 2.1-76) and established HIV-1 infection (794; 494
      1,029) (Kruskal-Wallis, p<0.0001). CONCLUSIONS: The ARCHITECT combo assay with
      Multispot confirmation and reserved use of HIV-1 WB, HIV-2 Immunoblot and HIV
      NAAT for Multispot dual HIV-1/2 infection, and NAAT alone for Multispot-negative
      specimens, had a suitable test performance for detecting acute and established
      HIV infection.

PMID- 24029687
TI  - TGF-beta signaling in stromal cells acts upstream of FGF-10 to regulate
      epithelial stem cell growth in the adult lung.
AB  - Tissue resident mesenchymal stromal cells (MSCs) contribute to tissue
      regeneration through various mechanisms, including the secretion of trophic
      factors that act directly on epithelial stem cells to promote epithelialization.
      However, MSCs in tissues constitute a heterogeneous population of stromal cells
      and different subtypes may have different functions. In this study we show that
      CD166(neg) and CD166(pos) lung stromal cells have different proliferative and
      differentiative potential. CD166(neg) lung stromal cells exhibit high
      proliferative potential with the capacity to differentiate along the
      lipofibroblastic and myofibroblastic lineages, whereas CD166(pos) lung stromal
      cells have limited proliferative potential and are committed to the
      myofibroblastic lineage. Moreover, we show that CD166(pos) lung stromal cells do
      not share the same epithelial-supportive capacity as their CD166(neg)
      counterparts, which support the growth of lung epithelial stem cell (EpiSPC)
      colonies in vitro. In addition, ex vivo expansion of lung stromal cells also
      resulted in the loss of epithelial-supportive capacity, which could be reinstated
      by inhibition of the TGF-beta signaling pathway. We show that epithelial
      supportive capacity correlated with the level of FGF-10 expression and the
      reactivation of several lung development-associated genes. In summary, these
      studies suggest that TGF-beta signaling in stromal cells acts upstream of FGF-10
      to regulate epithelial stem cell growth in the adult lung. 

PMID- 24029688
TI  - Vertically integrated (Ga, In)N nanostructures for future single photon emitters
      operating in the telecommunication wavelength range.
AB  - Important technological steps are discussed and realized for future room
      temperature operation of III-nitride single photon emitters. First, the growth
      technology of positioned single pyramidal InN nanostructures capped by Mg-doped
      GaN is presented. The optimization of their optical characteristics towards
      narrowband emission in the telecommunication wavelength range is demonstrated. In
      addition, a device concept and technology was developed so that the
      nanostructures became singularly addressable. It was found that the nanopyramids
      emit in the telecommunication wavelength range if their size is chosen
      appropriately. A p-GaN contacting layer was successfully produced as a cap to the
      InN pyramids and the top p-contact was achievable using an intrinsically
      conductive polymer PEDOT:PSS, allowing a 25% increase in light transmittance
      compared to standard Ni/Au contact technology. Single nanopyramids were
      successfully integrated into a high-frequency device layout. These decisive
      technology steps provide a promising route to electrically driven and room
      temperature operating InN based single photon emitters in the telecommunication
      wavelength range. 

PMID- 24029689
TI  - Parkin plays a role in sporadic Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a chronic progressive neurologic
      disorder, which affects approximately one million men and women in the US alone.
      PD represents a heterogeneous disorder with common clinical manifestations and,
      for the most part, common neuropathological findings. OBJECTIVE: This short
      article reviews the role of the ubiquitin E3 ligase in sporadic PD. METHODS: The
      role of parkin in sporadic PD was reviewed by querying PubMed. RESULTS: Parkin is
      inactivated in sporadic PD via S-nitrosylation, oxidative and dopaminergic
      stress, and phosphorylation by the stress-activated kinase c-Abl, leading to the
      accumulation of AIMP2 and PARIS (ZNF746). CONCLUSION: Strategies aimed at
      maintaining parkin in a catalytically active state or interfering with the
      toxicity of AIMP2 and PARIS (ZNF746) offer new therapeutic opportunities.

PMID- 24029690
TI  - Risk assessment of manufacturing equipment surfaces contaminated with DDTs and
      dicofol.
AB  - Decommissioning of manufacturing plant in the chemical industry includes
      inspection of the surfaces of production equipment for potential contamination
      and associated health risks. In the present study wipe-samples were taken from
      the surfaces of dicofol manufacturing equipment at a chemical factory in north
      China and analyzed for chemicals of concern (COCs). Occupational hygiene
      assessment was conducted to assess the risks to demolition workers and health
      risk assessment was performed to evaluate the risks to demolition and general
      industrial workers. The concentrations of COCs on the equipment surfaces were
      found to be 0.54-3.75 * 10(4)mg DDTs m(-2) and 0.15-4.38 * 10(3)mg dicofolm(-2).
      The average concentration of p,p'-DDT does not represent an unacceptable risk to
      the demolition workers using occupational hygiene assessment. Under the
      industrial scenario the carcinogenic risks of COCs ranged from 2.28 * 10(-7) to
      1.79 * 10(-2) for p,p'-DDT, 6.18 * 10(-7) to 3.04 * 10(-3) for p,p'-DDD and 1.89
      * 10(-6) to 0.16 for p,p'-DDE. The non-carcinogenic hazard indices ranged from
      3.86 * 10(-3) to 3.03 * 10(2) for p,p'-DDT and 1.16 * 10(-3) to 33.94 for
      dicofol. Both carcinogenic risk and hazard index of COCs under the industrial
      scenario were higher than under the demolition scenario. Oral ingestion and
      dermal contact were the major pathways and accounted for >88% of the total
      exposure of COCs. Parameter sensitivity analysis shows that equipment surface
      concentration (Cs), frequency of contact with surface (EV), fraction of dust
      transferred from surface to skin (FTss) and exposure frequency (EF) were the most
      sensitive parameters and these should be acquired on a site-specific basis. The
      accuracy of the risk assessment was controlled largely by the variation in the
      sensitive parameters and the uncertainty of the exposure model for the inhalation
      pathway.

PMID- 24029691
TI  - Aggregation and disaggregation of ZnO nanoparticles: influence of pH and
      adsorption of Suwannee River humic acid.
AB  - The surface charge and average size of manufactured ZnO nanoparticles (NPs) were
      studied as a function of pH to understand the aggregation behavior and importance
      of the electrostatic interactions in solution. The interactions between ZnO and
      Suwannee River humic acid (SRHA) were then investigated under a range of
      environmentally relevant conditions with the ZnO nanoparticles pHPZC as the point
      of reference. The anionic charges carried by aquatic humic substances were found
      to play a major role in the aggregation and disaggregation of ZnO nanoparticles.
      At low concentrations of SRHA (<0.05 mg/L) and below the pHPZC, anionic SRHA was
      rapidly adsorbed onto the positively charged ZnO NPs hence promoting aggregation.
      With similar SHRA concentrations, at pHPZC, SRHA was able to control the
      suspension behavior of the ZnO and promote partial disaggregation in small
      volumes. This was more distinguishable when the pH was greater than pHPZC as SRHA
      formed a surface coating on the ZnO nanoparticles and enhanced stability via
      electrostatic and steric interactions. In most cases, the NP coating by SRHA
      induced disaggregation behavior in the ZnO nanoparticles and decreased the
      aggregate size in parallel to increasing SRHA concentrations. Results also
      suggest that environmental aquatic concentration ranges of humic acids largely
      modify the stability of aggregated or dispersed ZnO nanoparticles.

PMID- 24029692
TI  - A survey of emerging contaminants in the estuarine receiving environment around
      Auckland, New Zealand.
AB  - Increasing urbanisation in the future will put mounting stresses on the receiving
      environments around those urban centres due to increased sedimentation and
      contaminant runoff. Emerging contaminants (ECs) are an extensive array of
      chemicals and many are not under regulatory action. Within New Zealand likely
      future pressures from ECs will be in both urban centres and rural areas due to
      intensive agriculture, although at present there is a lack of information on the
      state of the environment in both sectors. This study was initiated to gauge the
      distribution of ECs in the urban environment by measuring concentrations of flame
      retardants, plasticisers, alkylphenols, herbicides and pesticides, steroid
      oestrogens, pharmaceuticals and heavy metals in sediment from 13 estuarine sites
      around Auckland, New Zealand's biggest city. Total polybrominated diphenyl ether
      (PBDE) flame retardant concentrations ((7)SigmaPBDE) ranged from 0.55 to 573 ng/g
      (dw). The phthalate plasticiser di(2-ethylhexyl)phthalate (DEHP) was measured at
      up to 11,500 ng/g from one site. Nonylphenol (NP) was found at up to 32,000 ng/g
      at one site adjacent to the city's major wastewater treatment plant (WWTP).
      However, median concentrations of NP were 153 ng/g, suggesting this site was not
      representative of the region. Nonylphenol mono- and di-ethoxylates (NPEO1,2) had
      highest concentrations (1600 ng/g) at a marina. Highest glyphosate concentrations
      (up to 950 ng/g) were observed at residential sites. Steroid oestrogens were
      detected at extremely low concentrations (maximum 2.2 ng/g), while all other
      pesticides or herbicides were not detected at any sites. Multi-residue analysis
      of 46 pharmaceuticals showed presence of 21 compounds at one or more sites, with
      average concentrations ranging from 0.16 to 7.66 ng/g. Generally, environmental
      concentrations of ECs were similar to those reported world-wide. However,
      comparisons for pharmaceuticals were problematic, due to very few studies on
      pharmaceutical concentrations in estuarine sediments, with most focussed on
      sewage and stream water phases.

PMID- 24029693
TI  - Municipal gravity sewers: an unrecognised source of nitrous oxide.
AB  - Nitrous oxide (N2O) is a primary ozone-depleting substance and powerful
      greenhouse gas. N2O emissions from secondary-level wastewater treatment processes
      are relatively well understood as a result of intensive international research
      effort in recent times, yet little information exists to date on the role of
      sewers in wastewater management chain N2O dynamics. Here we provide the first
      detailed assessment of N2O levels in the untreated influent (i.e. sewer network
      effluent) of three large Australian metropolitan wastewater treatment plants.
      Contrary to current international (IPCC) guidance, results show gravity sewers to
      be a likely source of N2O. Results from the monitoring program revealed hydraulic
      flow rate as a strong driver for N2O generation in gravity sewers, with microbial
      processes (nitrification and possibly denitrification) implicated as the main
      processes responsible for its production. Results were also used to develop a
      presumptive emission factor for N2O in the context of municipal gravity sewers.
      Considering the discrepancy with current IPCC Guidelines, further work is
      warranted to assess the scale and dynamics of N2O production in sewers elsewhere.

PMID- 24029694
TI  - Quantitative evaluation of lake eutrophication responses under alternative water
      diversion scenarios: a water quality modeling based statistical analysis
      approach.
AB  - China is confronting the challenge of accelerated lake eutrophication, where Lake
      Dianchi is considered as the most serious one. Eutrophication control for Lake
      Dianchi began in the mid-1980s. However, decision makers have been puzzled by the
      lack of visible water quality response to past efforts given the tremendous
      investment. Therefore, decision makers desperately need a scientifically sound
      way to quantitatively evaluate the response of lake water quality to proposed
      management measures and engineering works. We used a water quality modeling based
      scenario analysis approach to quantitatively evaluate the eutrophication
      responses of Lake Dianchi to an under-construction water diversion project. The
      primary analytic framework was built on a three-dimensional hydrodynamic,
      nutrient fate and transport, as well as algae dynamics model, which has
      previously been calibrated and validated using historical data. We designed 16
      scenarios to analyze the water quality effects of three driving forces, including
      watershed nutrient loading, variations in diverted inflow water, and lake water
      level. A two-step statistical analysis consisting of an orthogonal test analysis
      and linear regression was then conducted to distinguish the contributions of
      various driving forces to lake water quality. The analysis results show that (a)
      the different ways of managing the diversion projects would result in different
      water quality response in Lake Dianchi, though the differences do not appear to
      be significant; (b) the maximum reduction in annual average and peak Chl-a
      concentration from the various ways of diversion project operation are
      respectively 11% and 5%; (c) a combined 66% watershed load reduction and water
      diversion can eliminate the lake hypoxia volume percentage from the existing
      6.82% to 3.00%; and (d) the water diversion will decrease the occurrence of algal
      blooms, and the effect of algae reduction can be enhanced if diverted water are
      seasonally allocated such that wet season has more flows. 

PMID- 24029696
TI  - Chronic kidney disease and nonalcoholic Fatty liver disease proven by transient
      elastography.
AB  - BACKGROUND/AIM: Preliminary data suggest an association between chronic kidney
      disease (CKD) and non-alcoholic fatty liver disease (NAFLD). The aim of this
      study was to further investigate the association between NAFLD and decreased
      kidney function. METHODS: A total of 62 patients with CKD were enrolled in the
      study. Liver stiffness was used to detect liver fibrosis and CAP (controlled
      attenuation parameter) was used to detect and quantify liver steatosis
      (Fibroscan(r)). NAFLD was defined by CAP values >=238 dB.m(-1). RESULTS: CKD
      stage III was present in 29 patients (46.8%) and CKD stage IV in 33 patients
      (53.2%). Out of 62 CKD patients 53 (85.5%) had NAFLD and of these 14/53 patients
      (26.4%) had also liver stiffness >7 kPa. The severity of liver steatosis was
      positively correlated with serum creatinine (r=0.399;p<0.01) and CRP (r=0.261;
      p<0.05) and negatively correlated with eGFR (r=-0.413; p<0.01) and serum iron
      concentration (r=-0.365; p<0.01). CONCLUSION: The results suggest a high
      prevalence of NAFLD in CKD patients. The severity of liver steatosis is
      negatively correlated with kidney function. The study documents the value of
      ultrasonographic elastography as an effective non-invasive screening method for
      the diagnosis of NAFLD.

PMID- 24029695
TI  - Proteome of Rhipicephalus sanguineus tick saliva induced by the secretagogues
      pilocarpine and dopamine.
AB  - One dimensional gel electrophoresis was used to separate proteins from the saliva
      of Rhipicephalus sanguineus female ticks fed on rabbits. Gel slices were
      subjected to tryptic digestion and analyzed by reversed-phase HPLC followed by
      MS/MS analysis. The data were compared to a database of salivary proteins of the
      same tick and to the predicted proteins of the host. Saliva was obtained by
      either pilocarpine or dopamine stimulation of partially fed ticks.
      Electrophoretic separations of both yielded products that were identified by mass
      spectrometry, although the pilocarpine-derived sample was of much better quality.
      The majority of identified proteins were of rabbit origin, indicating the
      recycling of the host proteins in the tick saliva, including hemoglobin, albumin,
      haptoglobin, transferring, and a plasma serpin. The few proteins found that were
      previously associated with parasitism and blood feeding include 2 glycine-rich,
      cement-like proteins, 2 lipocalins, and a thyropin protease inhibitor. Among
      other of the 19 tick proteins identified, albeit with undefined roles, were SPARC
      and cyclophilin A. This catalog provides a resource that can be mined for
      secreted molecules that play a role in tick-host interactions. 

PMID- 24029697
TI  - Involvement of NR1, NR2A different expression in brain regions in anxiety-like
      behavior of prenatally stressed offspring.
AB  - Prenatal stress (PS) has been shown to be associated with anxiety. However, the
      underlying neurological mechanisms are not well understood. To determine the
      effects of PS on anxiety-like behavior in the adult offspring, we evaluated
      anxiety-like behavior using open field test (OFT) and elevated plus maze (EPM) in
      the 3-month offspring. Both male and female offspring showed a significant
      reduction of crossing counts in the center, total crossing counts, rearing counts
      and time spent in the center in the OFT, and only male offspring showed a
      decreased percentage of open-arm entries and open-arm time in open arms in the
      EPM. Additionally, expression of NR1 and NR2A subunit of N-methyl-D-aspartate
      receptor (NMDAR) in the hippocampus (HIP), prefrontal cortex (PFC) and striatum
      (STR) was studied. Our results showed that PS reduced NR1 and NR2A expression in
      the HIP, NR2A expression in the PFC and STR in the offspring. The altered NR1 and
      NR2A could have potential impact on anxiety-like behavior in the adult offspring
      exposed to PS.

PMID- 24029698
TI  - Phase-locked hippocampal theta-band responses are related to discriminative
      eyeblink conditioned responding.
AB  - Hippocampal electrophysiological oscillatory activity is undoubtedly related to
      learning and memory. The relative power of spontaneously occurring hippocampal
      theta (~4-8 Hz) oscillations predicts how fast and how well an animal will learn:
      more theta predicts faster acquisition of the conditioned response in eyeblink
      conditioning in both rats and rabbits. Here, our aim was to study how hippocampal
      theta-band responses to conditioned stimuli elicited during very-long delay
      discrimination eyeblink conditioning relate to the accompanying conditioned
      behavior. We trained adult male New Zealand White rabbits using 1500-ms auditory
      stimuli as conditioned stimuli and a 100-ms airpuff as an unconditioned stimulus.
      The reinforced conditioned stimulus overlapped and co-terminated with the
      unconditioned stimulus whereas the non-reinforced conditioned stimulus was always
      presented alone. Consistent with previous results, hippocampal theta-band
      responses to the conditioned stimuli diminished in amplitude across training.
      Interestingly, hippocampal theta-band responses were most consistently time
      locked when a well-trained animal failed to suppress behavioral learned responses
      to the non-reinforced conditioned stimulus. We suggest that phase-locking of
      hippocampal theta-band oscillations in response to external stimuli reflects
      retrieval of the dominant memory trace (adaptive or not) along with initiating
      the most prominent action scheme related to that memory trace.

PMID- 24029700
TI  - Paradoxical enhancement of fear expression and extinction deficits in mice
      resilient to social defeat.
AB  - The exposure to stress has been associated with increased depressive and anxiety
      symptoms, yet not all individuals respond negatively to the experience of stress.
      Recent rodent social defeat models demonstrate similar individual differences in
      response to social stress. In particular, mice subjected to chronic social defeat
      have been characterized as being either "susceptible" or "resilient" by the level
      of social interaction following social defeat. Susceptibility is associated with
      lasting social avoidance as well as increased anxiety-like behavior, and
      depressive-like symptoms. Resilient animals, however, do not show social
      avoidance or increased depressive-like symptoms, but retain increased anxiety
      like behavior. Thus, it is unclear what "resilience" as measured by social
      interaction represents in terms of an overall behavioral and physiological
      phenotype. Here, we use an acute social defeat procedure, which produces distinct
      behavioral phenotypes in social interaction with no apparent changes in anxiety
      like behavior. Susceptible mice display lasting social avoidance, whereas
      resilient mice display normal social interaction. Susceptible mice also displayed
      deficits in fear extinction retention but had normal within-session extinction.
      Paradoxically, resilience was associated with enhanced fear expression, and
      severe deficits in fear extinction and extinction retention beyond that observed
      in susceptible mice. These effects in resilient mice were only apparent after the
      experience of social stress and were not due to impaired behavioral flexibility.
      These data suggest that mechanisms controlling resilience to acute social defeat
      as characterized by social interaction leave animals vulnerable to maladaptive
      fear behavior. 

PMID- 24029701
TI  - Reversible cerebral vasoconstriction syndrome after chewing khat leaves.

PMID- 24029699
TI  - Functional imaging of implicit marijuana associations during performance on an
      Implicit Association Test (IAT).
AB  - This research evaluated the neural correlates of implicit associative memory
      processes (habit-based processes) through the imaging (fMRI) of a marijuana
      Implicit Association Test. Drug-related associative memory effects have been
      shown to consistently predict level of drug use. To observe differences in neural
      activity of associative memory effects, this study compared 13 heavy marijuana
      users and 15 non-using controls, ranging in age from 18 to 25, during performance
      of a marijuana Implicit Association Test (IAT). Group by condition interactions
      in the putamen, caudate, and right inferior frontal gyrus were observed. Relative
      to non-users, marijuana users showed greater bilateral activity in the dorsal
      striatum (caudate and putamen) during compatible trials focused on perceived
      positive outcomes of use. Alternatively, relative to the marijuana-using group,
      the non-users showed greater activity in the right inferior frontal gyrus during
      incompatible trials, which require more effortful processing of information.
      Further, relative to fixation, heavy users showed bilateral activity in the
      caudate and putamen, hippocampus and some frontal regions during compatible
      trials and no significant activity during incompatible trials. The non-using
      group showed greater activity in frontal regions during incompatible trials
      relative to fixation and no significant activity during compatible trials. These
      findings are consistent with a dual process framework of appetitive behaviors
      proposing that (1) implicit associations underlying habit are mediated through
      neural circuitry dependent on the striatum, and (2) deliberative/controlled
      behaviors are mediated through circuitry more dependent on the prefrontal cortex.

PMID- 24029702
TI  - Revisiting the role of GCNF in embryonic development.
AB  - GCNF (NR6A1) is essential for embryonic development. GCNF belongs to the nuclear
      receptor (NR) gene family, it is distantly related to other NRs and is the only
      member of subfamily 6. As the ligand for GCNF has not been identified, GCNF is
      designated an orphan nuclear receptor. GCNF has been found to be a
      transcriptional repressor, through specific binding to DR0 response elements,
      which is found in the Oct4 proximal promoter for example. GCNF is expressed
      widely in early mouse embryos, and later in the developing nervous system. GCNF
      knockout mouse embryos die around E10.5. GCNF is required for the restriction of
      Oct4 expression to primordial germ cells after gastrulation. GCNF is expressed in
      ES/EC cells and during their differentiation, and has been reported to be
      required for pluripotency gene repression during retinoic acid (RA)-induced mES
      cell differentiation. GCNF can interact with DNA methylation proteins, and is
      suggested to recruit DNA methylation complexes to repress and silence Oct4
      expression. Nuclear receptor regulation in embryonic development is a complex
      process, as different nuclear receptors have overlapping and distinct functions.
      In-depth exploration of GCNF function and mechanism of action will help to
      comprehensively understand the nuclear receptor regulation in embryonic
      development. 

PMID- 24029703
TI  - Modelling the expected rate of laboratory biosafety breakdowns involving
      rinderpest virus in the post-eradication era.
AB  - Now that we are in the rinderpest post-eradication era, attention is focused on
      the risk of re-introduction. A semi-quantitative risk assessment identified
      accidental use of rinderpest virus in laboratories as the most likely cause of re
      introduction. However there is little data available on the rates of laboratory
      biosafety breakdowns in general. In addition, any predictions based on past
      events are subject to various uncertainties. The aims of this study were
      therefore to investigate the potential usefulness of historical data for
      predicting the future risk of rinderpest release via laboratory biosafety
      breakdowns, and to investigate the impacts of the various uncertainties on these
      predictions. Data were collected using a worldwide online survey of laboratories,
      a structured search of ProMED reports and discussion with experts. A stochastic
      model was constructed to predict the number of laboratory biosafety breakdowns
      involving rinderpest that will occur over the next 10 years, based on: (1) the
      historical rate of biosafety breakdowns; and (2) the change in the number of
      laboratories that will have rinderpest virus in the next 10 years compared to
      historically. The search identified five breakdowns, all of which occurred during
      1970-2000 and all of which were identified via discussions with experts. Assuming
      that our search for historical events had a sensitivity of over 60% and there has
      been at least a 40% reduction in the underlying risk (attributable to decreased
      laboratory activity post eradication) the most likely number of biosafety events
      worldwide was estimated to be zero over a 10 year period. However, the risk of at
      least one biosafety breakdown remains greater than 1 in 10,000 unless the
      sensitivity was at least 99% or the number of laboratories has decreased by at
      least 99% (based on 2000-2010 during which there were no biosafety breakdowns). 

PMID- 24029704
TI  - CDX2 may be a useful marker to distinguish primary ovarian carcinoid from
      gastrointestinal metastatic carcinoids to the ovary.
AB  - Primary ovarian carcinoids and metastatic tumors share similar morphologic
      features. Metastatic carcinoids must be excluded from primary ones for prognostic
      and therapeutic reasons. Gastrointestinal neuroendocrine (carcinoid) tumors are
      much more common with the majority arising from small intestine and appendix. The
      aim of this study is to evaluate the role of immunohistochemistry for CDX2 in
      differentiating primary ovarian from metastatic carcinoids of primary
      gastrointestinal origin. Thirty primary pure ovarian carcinoids, 16 primary
      ovarian carcinoids arising in association with benign teratomas, 10 ovarian
      carcinoids metastatic from primary gastrointestinal tract and 70 gastrointestinal
      neuroendocrine tumors were studied for the expression of CDX2 by
      immunohistochemistry. CDX2 expression revealed that 40 (57.1%) of 70 cases of
      gastrointestinal carcinoids and 9 (90%) of 10 ovarian metastatic carcinoids
      showed positive nuclear staining (diffuse or focal). On the other hand, 3 (18.8%)
      of 16 primary carcinoids with teratomatous elements showed weak positivity. Among
      the 70 gastrointestinal carcinoids, CDX2 was positive in 38 (90.5%) of 42 cases
      in the duodenum, small intestine, appendix, and only in 2 (11.8%) of 17 cases of
      colorectal carcinoids and none of the 11 cases in the stomach. It is concluded
      that CDX2 may be a useful marker to distinguish primary ovarian carcinoid from
      metastasis from small intestinal and appendiceal neuroendocrine tumors. 

PMID- 24029705
TI  - Immunohistochemical analysis of chromogranin A and p53 expressions in ulcerative
      colitis-associated neoplasia: neuroendocrine differentiation as an early event in
      the colitis-neoplasia sequence.
AB  - Pancellular dysplasia involving neuroendocrine cells has been shown to be
      comparatively rare but crucially implicated in the development of neuroendocrine
      tumors in ulcerative colitis (UC). We attempted to clarify the prevalence of
      chromogranin A expression as a marker of neuroendocrine differentiation in UC
      associated neoplasia by immunohistochemical analyses of 26 lesions of low-grade
      dysplasia (LGD), 32 high-grade dysplasias (HGDs) and 27 invasive cancers (INVs),
      along with p53 expression. We additionally assessed the utility of these proteins
      for differential diagnosis between LGD and HGD. Chromogranin A was considered
      positive when immunoreactive cells were more than 5% of neoplastic lesions, and
      the positivity tended to be higher in HGDs (57.7%) or INVs (46.7%) than LGDs
      (32.0%). Focal or diffuse nuclear staining for p53 was defined as positive. The
      positive rate for p53 was also higher in HGDs (59.4%; P = 0.037) or INVs (59.3%)
      than LGDs (30.8%). A similar trend was found in co-positivity for both proteins
      (HGDs, 30.7%/INVs, 26.7% versus LGDs, 12.0%). No positivity for both proteins was
      identified in the non-neoplastic mucosa. The combination of the two proteins
      improved the sensitivity (66.7%), specificity (80.0%), positive predictive value
      (72.7%) and negative predictive value (75.0%) for HGD as compared to p53 alone
      (sensitivity, 57.7%; specificity 68.0%; positive predictive value, 65.2%;
      negative predictive value, 60.7%). In conclusion, we show here that
      neuroendocrine differentiation is relatively common and represents an early event
      in the UC-neoplasia pathway in which p53 and chromogranin A are coordinately up
      regulated. Immunohistochemical assessment of their expression might provide a
      useful adjunct tool for grading dysplasia in UC. 

PMID- 24029706
TI  - Clinicopathologic features of ductal carcinoma in situ in young women with an
      emphasis on molecular subtype.
AB  - Young women with ductal carcinoma in situ treated by breast-conserving therapy
      have a higher recurrence rate than do older women, and a younger age at diagnosis
      is associated with worse overall survival after recurrence. This study explores
      the clinical, pathologic, and immunohistochemical characteristics of ductal
      carcinoma in situ lesions diagnosed in women 40 years and younger with a focus on
      molecular subtypes to elucidate features that may contribute to the purported
      worse outcome for this patient population. Forty-one patients diagnosed with
      ductal carcinoma in situ at age 40 years and younger were identified over a 10
      year period; 31 cases were used to construct tissue microarrays. The microarrays
      were labeled with antibodies to estrogen receptor, progesterone receptor, HER2,
      Ki-67, CK5/6, epidermal growth factor receptor, and p53 and subsequently
      classified as luminal A, luminal B, HER2, basal-like, or unclassifiable triple
      negative. All patients had high-grade (73.2%) or intermediate-grade (26.8%)
      ductal carcinoma in situ. The molecular subtype breakdown was 61.3% luminal A,
      22.6% luminal B, 13% HER2, and 3.1% unclassifiable triple negative. The mean Ki
      67 by subtype was 4.2%, 14%, 9.5%, and 50%, respectively. Mastectomy was
      performed in 33 patients (80%). Eight patients (20%) underwent excisional biopsy
      without subsequent mastectomy. In addition to a predominance of high-grade
      lesions, young patients had a high proportion of luminal B subtype, which may
      contribute to an increased rate of local recurrence in this population. A larger
      series is necessary to confirm the impact that the molecular subtypes of ductal
      carcinoma in situ in younger patients might have on outcome. 

PMID- 24029707
TI  - Immunohistochemical and molecular characterization of clear cell carcinoma of the
      lung.
AB  - The diagnostic entity of clear cell carcinoma of the lung (CCCL) is
      controversial, with many investigators arguing against its inclusion in the World
      Health Organization classification of lung carcinoma. Because of its rarity and
      questions regarding its histogenesis, I studied 3 groups of carcinomas with
      immunohistochemical and molecular assays, including 6 cases of CCCL, 7 cases of
      adenocarcinoma with clear cell change, and 11 cases of squamous carcinomas with
      prominent clear cell change. CCCL tended to be present in older individuals with
      an adenocarcinoma immunophenotype (cytokeratin 7 and TTF1 positivity). Molecular
      analysis by Sanger sequencing revealed KRAS mutations in 5 of 6 cases of CCCL, 2
      of 7 adenocarcinomas with clear cell change, and 2 of 11 squamous carcinomas with
      clear cell change. Although perhaps not a distinct pathologic entity, in this
      pilot study, CCCL has an immunophenotype similar to solid-type adenocarcinoma
      with clear cell change and displays more frequent and unusual KRAS mutations than
      expected in most adenocarcinomas of the lung. 

PMID- 24029708
TI  - Observer variability in the histopathologic diagnosis of microscopic colitis and
      subgroups.
AB  - The diagnosis of microscopic colitis (MC) is based on histologic findings and
      includes collagenous colitis (CC) and lymphocytic colitis (LC). Incomplete MC
      (MCi) denotes patients with chronic diarrhea and a normal endoscopy and
      morphological changes that do not completely meet the histologic criteria of LC
      or CC. The aim of this study was to investigate the intraobserver and
      interobserver agreement on the MC subtypes of CC, LC, and MCi and the ability to
      discriminate MCi from normal and inflammatory bowel disease/nonspecific reactive
      changes. A single hematoxylin and eosin-stained specimen from biopsies of the
      following 5 groups were randomly selected and blinded: CC, LC, MCi, inflammatory
      bowel disease, and normal. Three pathologists independently reviewed the
      specimens. The specimens were relabeled and reinterpreted 4 months later.
      Intraobserver and interobserver agreement was evaluated by kappa statistics.
      kappa values for intraobserver agreement were good for 5 diagnostic groups
      varying from 0.70 to 0.83 and very good when simplifying to only 3 diagnostic
      groups varying from 0.88 to 0.96, separating MC/MCi from non-MC. kappa values for
      interobserver agreement varied from 0.60 to 0.75 for 5 diagnostic groups and 0.81
      to 0.89 for 3 diagnostic groups. The study shows that the intraobserver and
      interobserver agreement is high for discriminating between MC/MCi and non-MC,
      whereas the ability to discriminate MCi from CC and LC is lower. A revision and
      consensus on the histologic criteria of the MC subtypes seem warranted. 

PMID- 24029709
TI  - B cells in classical Hodgkin lymphoma are important actors rather than bystanders
      in the local immune reaction.
AB  - Recent studies, largely focusing on cellular immunity, have demonstrated that the
      composition of the abundant inflammatory background of Hodgkin lymphoma may
      affect outcome. This investigation aimed to characterize the potential role of
      infiltrating B cells and follicular dendritic cell networks in classical Hodgkin
      lymphoma (cHL) to better assess the role of components of humoral immunity. One
      hundred two cHL biopsies were investigated by immunohistochemistry with
      antibodies specific for CD20, CD138, activation-induced cytidine deaminase, and
      CD21 to characterize B cell distribution and follicular structures. To further
      subclassify B cells, analyses of tissue microarrays were performed investigating
      the expression of Mum1, Bcl6, IgD, IgG, IgG4, IgM, T-bet, CD38, CD5, and CD10.
      For evaluation a computer assisted quantification method was compared with a
      scoring system. Survival analysis and correlation analysis were performed. The B
      cell infiltrate was dominated by CD20+ B cells, followed by plasma cells, whereas
      only few AID+ cells were observed. High numbers of CD21+ follicular dendritic
      cell networks, CD20+ B cells, IgM+ cells, CD20+ aggregates, and Bcl6+ cells were
      associated with a better outcome of cHL patients, whereas Pax5+/CD38+ cells had
      an adverse prognostic impact. Other parameters showed no influence on survival.
      Our findings suggest that a complex network of B cells is present in the
      microenvironment of cHL and that B cells might actively contribute to a local
      anti- as well as pro-tumoral immune response. This indicates that the network of
      B cells in tumors is probably just as diverse as the T cellular infiltrate and
      probably functionally as heterogenous. 

PMID- 24029710
TI  - Mammaglobin and S-100 immunoreactivity in salivary gland carcinomas other than
      mammary analogue secretory carcinoma.
AB  - Mammary analogue secretory carcinoma (MASC) is a recently described salivary
      gland tumor that has morphologic features similar to secretory carcinoma of the
      breast and that also harbors the same ETV6 translocation. Diffuse mammaglobin and
      S-100 immunoreactivity are used to differentiate MASC from its morphologic
      mimics, especially acinic cell carcinoma and adenocarcinoma, not otherwise
      specified. However, the combination of mammaglobin and S-100 immunoreactivity has
      not been well studied in other types of salivary gland carcinomas that may have
      focal areas reminiscent of MASC. Here we evaluated mammaglobin and S-100
      immunoreactivity in 15 cases each of polymorphous low-grade adenocarcinoma,
      adenoid cystic carcinoma and mucoepidermoid carcinoma, and also in 2 cases of
      adenocarcinoma, not otherwise specified, and 1 mucinous adenocarcinoma. Cases
      with significant co-expression of mammaglobin and S-100 (moderate or strong
      immunoreactivity in >25% of tumor cells) were further analyzed by fluorescence in
      situ hybridization using the ETV6 (12p13) break-apart probe. Nine cases (60%) of
      polymorphous low-grade adenocarcinoma and two (13.3%) of adenoid cystic carcinoma
      met the criteria for significant co-expression of mammaglobin and S-100. All were
      negative for the ETV6 translocation by fluorescence in situ hybridization.
      Although mammaglobin and S-100 positivity was seen in the majority of
      polymorphous low-grade adenocarcinomas and a minority of adenoid cystic
      carcinomas, none were positive for the ETV6 translocation characteristic of MASC.
      This indicates a need for caution in the use of immunohistochemistry for
      diagnosing MASC, especially in the absence of cytogenetic confirmation. 

PMID- 24029711
TI  - Utility of ProEx C in the histologic evaluation of the neoplastic and
      nonneoplastic urothelial lesions.
AB  - ProEx C is an antibody cocktail targeting the expression of topoisomerase IIalpha
      and minichromosome maintenance protein 2. ProEx C staining is being used mainly
      to assist in diagnoses of dysplasia in gynecological specimens. This study was
      designed to determine the utility of ProEx C in assessing the urothelial lesions.
      Sixty-four patient specimens were divided into 5 groups: group I, 22 benign;
      group II, 13 low-grade noninvasive papillary urothelial carcinoma; group III, 10
      high-grade urothelial carcinoma in situ (flat lesion); and group IV, 19 high
      grade noninvasive papillary and invasive urothelial carcinomas. ProEx C reactions
      were scored in basal, parabasal, intermediate, and superficial cell layers. A
      sample was recorded as positive when nuclear staining was seen in the cells of
      the intermediate and/or superficial layers. Of 22 cases in group I, 21 were
      negative for ProEx C with a specificity of 95%. Of 13 cases in group II, 11 had
      positive results with sensitivity of 85%. All cases in groups III and IV had
      positive staining pattern with ProEx C with a sensitivity of 100%. In this study,
      ProEx C stain had an overall 95% sensitivity and specificity with positive and
      negative predictive values of 98% and 91%, respectively, for detection of
      urothelial carcinoma. We conclude that ProEx C is effective in differentiating
      carcinoma in situ and benign urothelial lesions. It also resolves issues in low-
      versus high-grade papillary urothelial carcinomas. To our knowledge, this is the
      first publication on the diagnostic application of ProEx C in histopathology of
      the urothelial lesions. 

PMID- 24029712
TI  - Circulating markers of endothelial dysfunction and platelet activation in
      patients with severe symptomatic cerebral small vessel disease.
AB  - BACKGROUND: Small deep infarcts (SDI), also called lacunar infarcts, resulting
      from the occlusion of deep branch arteries, account for 25% of ischemic strokes.
      The physiopathology of the disease remains largely unknown. However, evidence
      about the role of endothelial dysfunction has emerged. Whereas chronic platelet
      activation is of major importance in acute thrombosis of large atherosclerotic
      arteries, its role in SDI remains unclear. Frequently associated risk factors are
      hypertension and diabetes mellitus. The aim of this study was to determine
      platelet and endothelial activation in patients with recent SDI in comparison to
      population-based control subjects matched for age, sex and vascular risk factors.
      METHODS: Platelet activation markers (activated glycoprotein IIb/IIIa, P-selectin
      and platelet microparticles), shear-induced platelet aggregation (SIPA) studied
      in the SIPAgreg device at 4,000 s(-1), endothelial activation markers [including
      von Willebrand factor (vWF) antigen and homocysteine] and high-sensitivity C
      reactive protein (hsCRP) were measured in 74 consecutive patients with recent
      SDI, in whom detectable large artery atherosclerosis or cardiac embolism had been
      ruled out. Blood samples were collected 1 and 3 months after symptom onset. These
      factors were also measured in 74 population-based controls with no stroke history
      and matched for age, sex, hypertension and diabetes. RESULTS: One month after
      symptom onset, the patients had similar levels of platelet activation to matched
      controls (p > 0.40 for all comparisons). In contrast, endothelial activation
      parameters were increased in patients in comparison to controls (vWF: p = 0.002
      and homocysteinemia/creatinemia: p = 0.025). The level of hsCRP was slightly
      increased in patients compared to controls (p = 0.059). At 3 months, we observed
      a significant decrease in vWF and hsCRP levels in patients (median change in vWF
      = 10%, p = 0.004; median change in hsCRP = 0.4 mg/l, p = 0.02). Homocysteine
      levels and all platelet parameters remained unchanged at this time compared to at
      1 month. CONCLUSIONS: Our results confirm that chronic platelet activation, when
      compared to controls matched for age, sex and vascular risk factors, did not seem
      to play a central role in the pathophysiology of lacunar stroke. In contrast, we
      found markers of endothelial dysfunction, the role of which in the occurrence of
      lacunar infarction has still to be clarified in further studies.

PMID- 24029713
TI  - A molecular study of tick-borne haemoprotozoan parasites (Theileria and Babesia)
      in small ruminants in Northern Tunisia.
AB  - In this study, the frequency of Theileria and Babesia species in sheep and goats
      was assessed via reverse line blotting (RLB). A total of 263 apparently healthy
      sheep and goats, from 16 randomly selected flocks located in 9 localities
      situated in 3 bioclimatic zones in Tunisia, were investigated for the blood
      protozoans. RLB hybridization with polymerase chain reaction detected only
      Theileria ovis in sheep and goats, accounting for 22.4% (95% confidence interval
      [CI]: 17.6-27.1%) positive samples. The infection rate in sheep (28.1%; 95% CI:
      23.8-32.3%) was higher than in goats (4.7%; 95% CI: -10.9 to 20.4%). Neither
      Babesia nor mixed infections were detected. Only two Ixodid tick species
      (Rhipicephalus turanicus and Rhipicephalus bursa) were collected from the
      examined sheep and goats in 5 localities. R. turanicus was the dominant species
      (95.5%) collected mainly in the humid zone, while apparently rare in the sub
      humid zone. R. bursa was the only species collected in the semi-arid area. RLB
      analysis identified six different piroplasms in ticks, with an overall prevalence
      of 31.5% (95% CI: 28.1-34.9%). Twenty percent (95% CI: 14.4-25.5%) of the
      collected ticks tested positive for Theileria spp., 3% (95% CI: -5.6 to 11.6%)
      for Babesia spp. and 0.9% (95% CI: -8.1 to 9.9%) of the ticks harbored both
      genera; several of these species are not known to occur in small ruminants. This
      is the first report on the detection of Theileria and Babesia species DNA in
      small ruminants and ticks in Tunisia.

PMID- 24029714
TI  - Hd86 mRNA expression profile in Hyalomma scupense life stages, could it
      contribute to explain anti-tick vaccine effect discrepancy between adult and
      immature instars?
AB  - Bm86 midgut protein has been used in order to control ticks of the Hyalomma
      genus. Previous studies demonstrated the inefficacity of this antigen in the
      control of Hyalomma scupense, whereas recombinant Hd86 antigen, the Bm86 ortholog
      in H. scupense produced in Pichia pastoris, was protective against larval H.
      scupense tick stage infestations but ineffective in the control of the adult
      stage. One possible explanation for this result is the variation in Hd86
      expression levels between these two developmental stages. To test this
      hypothesis, Hd86 mRNA levels were characterized in H. scupense developmental
      stages. The expression profile of Hd86 demonstrated a significant variation
      between tick life stages and showed a significant reduction in the number of
      transcripts during feeding and, particularly after molting to adults. The most
      interesting result was noted after molting of engorged nymphs in unfed adults
      where the expression levels decreased significantly by 12.78 (10.77-17.39)
      (p<0.001) and 9.25 (5.77-15.72)-fold (p<0.001) in unfed males and unfed females,
      respectively. Comparing unfed nymphs to unfed adult ticks, the Hd86 expression
      levels decreased by 13.82 (5.39-24.45) (p=0.035) and 9.93 (2.87-22.08)-fold
      (p=0.038) in males and females respectively. Lower Hd86 mRNA levels in adult
      ticks should result in lower protein levels and thus less antibody-antigen
      interactions necessary for vaccine efficacy in ticks fed on vaccinated animals.
      Thus, the observed differences in Hd86 expression profile between immature and
      adult stages might explain, in part, the discrepancy of the Hd86 vaccine efficacy
      against these two life stages of H. scupense.

PMID- 24029715
TI  - Molecular and parasitological detection of Trypanosoma evansi in Camels in
      Ismailia, Egypt.
AB  - Trypanosoma evansi (T. evansi) is an endemic disease of camels and other domestic
      animals in Egypt. This study aimed to determine the prevalence of clinical and
      sub-clinical T. evansi infection among camels in Ismailia, Egypt, as well as
      survey their owners for T. evansi infection. The diagnostic sensitivity of three
      different PCR assays for detection of T. evansi in blood samples was evaluated.
      Blood samples were collected from 100 camels and 20 of their owners in the
      Ismailia governorate. Results revealed that the percentage of infected of camels
      with T. evansi vary with the detection method, ranging from 10% to 46% by PCR
      compared to 12% by microscopic examination of stained blood smears. Targeting the
      highly repeated sequence of mini-chromosome satellite DNA (TBR1/2 primer set) was
      more often seen in the PCR method (46% positive) compared to targeting ITS 1 (16%
      positive) or RoTat 1.2 VSG (10% positive) sequences. A partial sequence of RoTat
      1.2 VSG gene was identical to the T. evansi sequences reported from India and
      Kenya, but varied similarity was seen when aligned with Egyptian T. evansi
      sequences. None of the camel owners were positive for T. evansi by microscopic
      examination of stained blood smears or PCR assays. PCR assay based on TBR sets is
      useful in the diagnosis and control disease and reducing economic losses. 

PMID- 24029716
TI  - Fish-borne trematodes in cultured Nile tilapia (Oreochromis niloticus) and wild
      caught fish from Thailand.
AB  - Fish-borne zoonotic trematode (FZT) infections affect the health of more than 18
      million people around the world, particularly in Asian countries. Nile tilapia
      (Oreochromis niloticus) is a white meat fish that has an increasing national and
      international market. The objective of this study was to determine the prevalence
      of FZT metacercarial infections in Nile tilapia from cage and pond aquaculture
      systems and in wild-caught fish from Suphan Buri, Nakhon Pathom and Chachoengsao
      provinces, Thailand. Fish were collected from four cages in Suphan Buri and four
      ponds in Nakhon Pathom provinces between September-October 2011 and April-May
      2012 and wild-caught fish were collected in May 2012. All fish were examined for
      metacercariae by a pepsin digestion and metacercariae identified using
      morphological and molecular methods. During the first sampling of tilapia the
      prevalence of metacercariae in cage culture fish were 2.5% and 10% in pond
      culture fish. During the second sampling, metacercariae was found in 2.0% of
      tilapia from cage and none from the ponds. Of the 150 wild-caught fish, a total
      of 80 (53.3%) were found to be infected with metacercariae, mostly the zoonotic
      species Stellantchasmus falcatus, Haplorchis pumilio and Procerovum varium. The
      results revealed a low risk for FZT in Nile tilapia cultured in cage and pond
      aquaculture systems. However, the high prevalence of FZT in wild-caught fish
      indicates a high potential for spillover from wild reservoir hosts and
      underscores the need for vigilance and good management practices by the
      aquaculture sector. 

PMID- 24029717
TI  - The use of combined anteversion in total hip arthroplasty for patients with
      developmental dysplasia of the hip.
AB  - The combined anteversion technique has been proposed recently and proved to be an
      applicable technique in general THA. The corresponding author routinely applied
      this approach to DDH patients in clinical practice. The current study aimed to
      provide clinical evidence for this approach. We studied 35 DDH patients (47
      hips). Every patient underwent pelvic CT scans before and after surgery and the
      HHs was recorded. The data indicate a high accuracy of controlling components
      orientation and satisfactory clinical outcomes. Using this approach, we reduced
      dislocation risk and got better impingement free range of motion. Therefore, we
      conclude that combined anteversion is effective for DDH patients who receive a
      THA. This approach could guarantee stable and functioning joints for DDH patients
      receiving THA. 

PMID- 24029718
TI  - Medium-term results of cementation of a highly cross-linked polyethylene liner
      into a well-fixed acetabular shell in revision hip arthroplasty.
AB  - The present study was undertaken to document outcomes of cementation of a highly
      cross-linked polyethylene (PE) liner into a well-fixed acetabular metal shell in
      36 hips. All operations were performed by a single surgeon using only one type of
      liner. Patients were followed for a mean of 6.1 years (range, 3-8 years). Mean
      Harris hip score improved from 58 points preoperatively to 91 points
      postoperatively. There were no cases of PE liner dislodgement or progressive
      osteolysis. 1 hip (2.8%) required revision surgery for acetabular cup loosening
      with greater trochanteric fracture. Complications included 1 peroneal nerve palsy
      and 1 dislocation. The results of this study and previous reports demonstrated
      that cementation of highly cross-linked PE liner into well-fixed metal shell
      could provide good midterm durability.

PMID- 24029719
TI  - Unpressurised cement acetabular liner (UCAL)--an additional technique for
      enhancing hip spacer performance.
AB  - First stage revision of an infected hip can be a complex procedure. Effective
      infection control may dictate leaving a skeletalised hip with bony defects.
      Decisions must be made to adapt to the intra-operative findings. It is important
      that the surgeon has many options to deal with the many potential challenges. The
      ideal spacer preserves the remaining bone stock but also allows articulation, is
      stable in doing so, delivers antibiotics locally, is resistant to breakage and is
      easily removed. Current spacer options struggle to achieve all of these goals.
      The use of an unpressurised cement acetabular liner (UCAL) is an additional
      option, which bestows a number of advantages. We describe two cases, which
      illustrate this. 

PMID- 24029720
TI  - Age as an independent risk factor for postoperative morbidity and mortality after
      total joint arthroplasty in patients 90 years of age or older.
AB  - The population of patients over 90 years of age has experienced the fastest
      growth in recent years. The number of primary total joint arthroplasties (TJA)
      has also been increasing. Our objectives were to examine in-hospital morbidity,
      mortality and resource consumption following primary TJA in patients older than
      89 years at the national level. Nationwide Inpatient Sample was used to identify
      8,340,167 patients who underwent TJA between 1993 and 2008, 58,355 (0.7%) were 90
      years of age or older. Older patients were at higher risk of developing cardiac
      (OR 2.5; 95% CI 2.4-2.6), neurological (OR 2.1; 95% CI 1.8-2.4), respiratory
      complications and higher risk of mortality (OR 11.5; 95% CI 10.93-12.1) after
      controlling for baseline comorbidities. Age is an independent risk factor for
      postoperative complications and mortality. Our data can be used to educate
      patients on the risks before undergoing primary TJA and aid physicians in
      assessing and adjusting perioperative risk.

PMID- 24029721
TI  - Improved efficiency of multi-criteria IMPT treatment planning using iterative
      resampling of randomly placed pencil beams.
AB  - This study investigates whether 'pencil beam resampling', i.e. iterative
      selection and weight optimization of randomly placed pencil beams (PBs), reduces
      optimization time and improves plan quality for multi-criteria optimization in
      intensity-modulated proton therapy, compared with traditional modes in which PBs
      are distributed over a regular grid. Resampling consisted of repeatedly
      performing: (1) random selection of candidate PBs from a very fine grid, (2)
      inverse multi-criteria optimization, and (3) exclusion of low-weight PBs. The
      newly selected candidate PBs were added to the PBs in the existing solution,
      causing the solution to improve with each iteration. Resampling and traditional
      regular grid planning were implemented into our in-house developed multi-criteria
      treatment planning system 'Erasmus iCycle'. The system optimizes objectives
      successively according to their priorities as defined in the so-called 'wish
      list'. For five head-and-neck cancer patients and two PB widths (3 and 6 mm sigma
      at 230 MeV), treatment plans were generated using: (1) resampling, (2)
      anisotropic regular grids and (3) isotropic regular grids, while using varying
      sample sizes (resampling) or grid spacings (regular grid). We assessed
      differences in optimization time (for comparable plan quality) and in plan
      quality parameters (for comparable optimization time). Resampling reduced
      optimization time by a factor of 2.8 and 5.6 on average (7.8 and 17.0 at maximum)
      compared with the use of anisotropic and isotropic grids, respectively. Doses to
      organs-at-risk were generally reduced when using resampling, with median dose
      reductions ranging from 0.0 to 3.0 Gy (maximum: 14.3 Gy, relative: 0%-42%)
      compared with anisotropic grids and from -0.3 to 2.6 Gy (maximum: 11.4 Gy,
      relative: -4%-19%) compared with isotropic grids. Resampling was especially
      effective when using thin PBs (3 mm sigma). Resampling plans contained on average
      fewer PBs, energy layers and protons than anisotropic grid plans and more energy
      layers and protons than isotropic grid plans. In conclusion, resampling resulted
      in improved plan quality and in considerable optimization time reduction compared
      with traditional regular grid planning. 

PMID- 24029722
TI  - Effect of liquid-handling accuracy on assay performance.
AB  - This study illustrates how optimization of both liquid-handling accuracy and
      precision is critical to assay performance. The study was designed to examine (1)
      liquid-handling performance and (2) the effect of liquid-handling variability on
      two types of in vitro biochemical assays by making small but deliberate changes
      to assay volume delivery. Specifically, protein binding (streptavidin) and enzyme
      (alpha-galactosidase) assays were investigated by determining the effect of assay
      volume for each assay component. The concomitant effect of the liquid-handling
      variability was then measured via inhibitor potency and assay performance
      characteristics such as Z-factor, signal-to-background, and variability. It was
      found that small changes in assay component volumes were indeed measurable by
      potency (IC50) but not necessarily by assay variability (Z-factor). In fact, this
      study demonstrates how a miscalibrated liquid handler can lead to erroneous data.

PMID- 24029723
TI  - Factors associated with meniscus repair in patients undergoing anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: Meniscus injuries are common in patients with anterior cruciate
      ligament (ACL) tears. Patient demographics, surgeon characteristics, and
      concurrent diagnostic factors affecting the prevalence of meniscus repairs in
      patients undergoing ACL reconstruction (ACLR) by community-based orthopaedic
      surgeons have not been fully studied. HYPOTHESIS: Patient (age, sex, race, and
      body mass index [BMI]), surgeon (sports medicine fellowship training status and
      case volume), and injury characteristics (1 or both menisci injured, injury
      location, and concurrent cartilage injury) and surgical venue (case volume) are
      associated with a higher likelihood of meniscus repair. STUDY DESIGN: Cross
      sectional study; Level of evidence, 3. METHODS: A cross-sectional study using
      data from a large community-based ACLR registry was performed. Patients with a
      meniscus injury and primary ACLR between February 2005 and June 2010 were
      included in the study. Meniscus repair rates by patient, surgeon, and injury
      characteristics were described. Associations were evaluated using generalized
      linear models. RESULTS: During the study period, 5712 primary ACLRs with a
      meniscus tear diagnosis were registered. There was 1 torn meniscus in 4248
      (74.4%) patients, and both menisci were torn in 1464 (25.6%) patients. Medial
      meniscus tears were repaired in 1192 (31.2%) of 3818 cases; the remaining 2626
      (68.8%) tears were not repaired, underwent alternative treatment (meniscectomy,
      trephination, rasped), or were left in situ. Lateral meniscus tears were repaired
      in 893 (26.6%) of 3358 cases; the remaining 2465 (73.4%) tears underwent
      alternative treatment or were left in situ. Adjusted models showed that younger
      patient age (P < .001), lower patient BMI (P < .001), surgeon's sports medicine
      fellowship training (P < .001), higher surgeon case volume (P < .001), higher
      surgical venue volume (P = .019), and medial meniscus tears (P < .001) were all
      associated with a higher likelihood of a meniscus repair. CONCLUSION: Younger
      patient age, lower patient BMI, surgeon's sports medicine fellowship training,
      higher surgeon case volume, and higher site volume are associated with a higher
      likelihood of a meniscus repair in patients undergoing primary ACLR in a large
      cohort from a community-based ACLR registry.

PMID- 24029724
TI  - Early multimodal rehabilitation following lumbar disc surgery: a randomised
      clinical trial comparing the effects of two exercise programmes on clinical
      outcome and lumbar multifidus muscle function.
AB  - BACKGROUND: The optimal components of postoperative exercise programmes following
      single-level lumbar discectomy have not been identified. Facilitating lumbar
      multifidus (LM) function after discectomy may improve postoperative recovery. The
      aim of this study was to compare the clinical and muscle function outcomes of
      patients randomised to receive early multimodal rehabilitation following lumbar
      discectomy consisting of exercises targeting specific trunk muscles including the
      LM or general trunk exercises. METHODS: We included participants aged 18 to 60
      years who were scheduled to undergo single-level lumbar discectomy. After two
      postoperative weeks, participants were randomly assigned to receive an 8-week
      multimodal exercise programme including either general or specific trunk
      exercises. The primary outcome was pain-related disability (Oswestry Index).
      Secondary outcomes included low back and leg pain intensity (0-10 numeric pain
      rating scale), global change, sciatica frequency, sciatica bothersomeness and LM
      function measured with real-time ultrasound imaging. Treatment effects 10 weeks
      and 6 months after surgery were estimated with linear mixed models. RESULTS: 61
      participants were randomised to receive a general trunk (n=32) or specific (n=29)
      exercise programme. There were no between-group differences in clinical or muscle
      function outcomes. Participants in both groups experienced improvements in most
      outcome measures. CONCLUSIONS: Following lumbar discectomy, multimodal
      rehabilitation programmes comprising specific or general trunk exercises have
      similar effects on clinical and muscle function outcomes. Local factors such as
      the individual patient characteristics identified by specific assessment
      findings, clinician expertise and patient preferences should direct therapy
      selection when considering the types of exercises tested in this trial for
      inclusion in rehabilitation programmes following lumbar disc surgery.

PMID- 24029725
TI  - Entering markets and bodies: increasing levels of the novel plasticizer
      Hexamoll(r) DINCH(r) in 24 h urine samples from the German Environmental Specimen
      Bank.
AB  - DINCH (diisononylcyclohexane-1,2-dicarboxylate) was introduced into the world
      market in 2002 as a non-aromatic plasticizer and phthalate substitute. We
      analyzed 300 urine samples (24 h voids) of the German Environmental Specimen Bank
      (ESB for Human tissues, ESB Hum) for specific DINCH metabolites by on-line HPLC
      MS/MS with isotope dilution quantification. Urine samples of the ESB Hum were
      from the years 1999, 2003, 2006, 2009 and 2012, chosen to investigate the
      appearance and a possible trend of DINCH exposure since its market introduction.
      No DINCH metabolites were detected in the 1999 and 2003 samples. From 2006 on,
      the percentage of samples with DINCH metabolites above the LOQ increased
      significantly over the years (7% in 2006, 43% in 2009 and 98% in 2012). The
      cyclohexane-1,2-dicarboxylic acid-mono(hydroxy-isononyl) ester (OH-MINCH) was the
      predominant metabolite. Median (and 95th percentile) concentrations (in MUg/l)
      increased from <LOQ (0.09) in 2006, to <LOQ (1.02) in 2009 to 0.39 (2.09) in
      2012. All oxidized DINCH metabolites (OH-MINCH, cx-MINCH, oxo-MINCH) correlated
      strongly among each other (rho>0.75, p<0.001). The median (95th percentile) DINCH
      intake in 2012 was calculated to be 0.14 (1.07)MUg/kg body weight/day which is
      considerably below daily intakes currently deemed tolerable. DINCH is regarded to
      have a preferred toxicological profile over certain anti-androgenic phthalates.
      The continuation of DINCH measurements in the ESB Hum and other human
      biomonitoring studies like the German Environmental Survey (GerES) allows
      tracking the development of DINCH body burdens, the distribution of exposure
      levels and daily intakes, providing basic data for future toxicological
      assessment and further epidemiological studies.

PMID- 24029726
TI  - Overlap in prevalence between various types of environmental intolerance.
AB  - Environmental intolerance (EI) is characterized by attribution of several,
      multisystem symptoms to specific environmental exposures, such as exposure to
      odorous/pungent chemicals, certain buildings, electromagnetic fields (EMFs) and
      everyday sounds. The symptoms are medically unexplained, non-specific and the
      symptoms overlap between different types of EI. To approach the issue of
      underlying mechanisms the matter of overlap in prevalence between intolerances
      can provide valuable information. The aim of the study was to examine if the
      overlap between intolerance to odorous/pungent chemicals, certain buildings, EMFs
      and sounds is larger than the expected overlap if no association would exist
      between them. The study was using cross-sectional data from the Vasterbotten
      Environmental Health Study in Sweden; a large questionnaire-based survey. 8520
      adults (18-79 years) were randomly selected after stratification for age and sex,
      of whom 3406 (40%) participated. Individuals with the four types of intolerance
      were identified either through self-report, or by having been physician-diagnosed
      with a specific EI. The overlaps between the four EIs were greater than
      predictions based on coincidence for both self-reported and diagnosed cases
      (except for the overlap between diagnosed intolerance to sounds and EMFs). The
      results raise the question whether different types of EI share similar underlying
      mechanisms, or at least that the sufferers of EI share some predisposition to
      acquire the conditions. 

PMID- 24029728
TI  - Large-scale fabrication and luminescence properties of GaN nanostructures by a
      soft UV-curing nanoimprint lithography.
AB  - GaN nanorods with a period of 400 nm and diameter of 200 nm, and nano-gratings
      with a period of 400 nm and gap width of 100 nm are fabricated on wafers by a
      soft UV-curing nanoimprint lithography. These nanostructures show high
      periodicity and good morphology. The photoluminescence (PL) spectra exhibit that
      the integral PL intensity of GaN nanorods is enhanced as much as 2.5 times,
      compared to that of as-grown GaN films. According to finite-difference time
      domain simulations and cathodoluminescence mappings, it is concluded that the
      enhancement for nanorods is due to the improvements of both spontaneous emission
      rate and light extraction efficiency caused by periodic GaN structures on the
      surface. By identifying the Raman shift of E1(TO) and E2(H) modes of GaN films
      with nano-gratings and nanorods, the normal-plane strain epsilon(zz) is
      determined. The PL emission energy is found to be proportional to the
      epsilon(zz), whose linear proportionality factor is calculated to be -27 meV GPa(
      1).

PMID- 24029727
TI  - Tau immunotherapy and imaging.
AB  - Disappointing findings from recent phase III trials on amyloid-beta (Abeta)
      immunotherapy for Alzheimer's disease (AD) have shifted the focus of such
      treatments to the tau protein. As tau pathology correlates better with the degree
      of dementia than Abeta plaque burden, it is a more attractive target once
      cognitive impairments are evident, while Abeta therapies may be better suited for
      the presymptomatic phase of the disease. Over 12 years ago, we initiated a tau
      immunotherapy program, seeking to alleviate the functional impairments associated
      with tau lesions in tauopathies. We have reported that various active and passive
      tau immunizations diminish tau pathology and improve function, including
      cognition, in different mouse models. Both extra- and intracellular pathways are
      likely involved. The antibodies may block the spread of tau pathology via
      microglial phagocytosis of the antibody-tau complex and facilitate lysosomal tau
      clearance in neurons after endosomal uptake. We have observed such antibody
      internalization following intracarotid injection in mice and in various culture
      models. These include brain slices and primary neurons from tangle mice as well
      as human neuroblastoma cell lines. Antibody targeting of different intracellular
      protein aggregates, including alpha-synuclein, Abeta and superoxide dismutase has
      been reported by others. Now, several laboratories have confirmed and extended
      our findings using various active and passive tau immunizations in different
      models, thereby clearly establishing the feasibility of this approach for
      clinical trials. We are also working on imaging approaches to monitor tau
      pathology, its consequences and the efficacy of treatments. Dire need exists for
      such diagnostic methods for tauopathies. Overall, therapies and diagnostic tools
      targeting tau pathology have a great potential for AD and other tauopathies.

PMID- 24029729
TI  - Hyperthyroid monkeys: a nonhuman primate model of experimental Graves' disease.
AB  - Graves' disease (GD) is a common organ-specific autoimmune disease with the
      prevalence between 0.5 and 2% in women. Several lines of evidence indicate that
      the shed A-subunit rather than the full-length thyrotropin receptor (TSHR) is the
      autoantigen that triggers autoimmunity and leads to hyperthyroidism. We have for
      the first time induced GD in female rhesus monkeys, which exhibit greater
      similarity to patients with GD than previous rodent models. After final
      immunization, the monkeys injected with adenovirus expressing the A-subunit of
      TSHR (A-sub-Ad) showed some characteristics of GD. When compared with controls,
      all the test monkeys had significantly higher TSHR antibody levels, half of them
      had increased total thyroxine (T4) and free T4, and 50% developed goiter. To
      better understand the underlying mechanisms, quantitative studies on
      subpopulations of CD4+T helper cells were carried out. The data indicated that
      this GD model involved a mixed Th1 and Th2 response. Declined Treg proportions
      and increased Th17:Treg ratio are also observed. Our rhesus monkey model
      successfully mimicked GD in humans in many aspects. It would be a useful tool for
      furthering our understanding of the pathogenesis of GD and would potentially
      shorten the distance toward the prevention and treatment of this disease in
      human.

PMID- 24029730
TI  - Chronic inflammation exacerbates glucose metabolism disorders in C57BL/6J mice
      fed with high-fat diet.
AB  - Inflammatory stress is closely related to metabolic disease and insulin
      resistance. The precise cellular mechanism linking obesity and diabetes is
      largely unknown, but about 14-20% of obese individuals develop diabetes. In this
      study, we investigated whether chronic inflammation exacerbated glucose
      metabolism disorder by impairing beta cell function in high-fat diet (HFD)-fed
      C57BL/6J mice. We used s.c. casein injection to induce chronic inflammation in
      HFD-fed C57BL/6J mice; 14 weeks on a HFD resulted in weight gain, hyperlipidemia,
      and low insulin sensitivity in these mice which nevertheless had normal blood
      glucose and serum inflammatory cytokines levels. Casein injection in the
      background of HFD elevated serum tumor necrosis factor alpha (TNFalpha) and serum
      amyloid A levels and increased TNFalpha and MCP1 expression in the adipose
      tissue, liver, and muscle of HFD-fed mice. Chronic inflammation induced by casein
      injection further decreased insulin sensitivity and insulin signaling, resulting
      in insulin deficiency and hyperglycemia in these mice. Islet mass and insulin
      content were markedly increased in HFD mice. However, in contrast with HFD-fed
      alone, chronic inflammation in HFD-fed mice decreased both islet mass and insulin
      content, reduced the genetic expression of insulin synthesis and secretion, and
      increased beta cell apoptosis. We conclude that chronic inflammation exacerbated
      glucose metabolism disorders by impairing beta cell function in HFD-fed C57BL/6J
      mice, suggesting that this mechanism may operate in obese individuals with
      chronic inflammation, making them prone to hyperglycemia. 

PMID- 24029731
TI  - Focal cortical subarachnoid hemorrhage revealed by recurrent paresthesias: a
      clinico-radiological syndrome strongly associated with cerebral amyloid
      angiopathy.
AB  - BACKGROUND: Focal subarachnoid hemorrhage (SAH) is often revealed by transient
      and recurrent focal neurological episodes. This cause is important to identify
      because it carries a high risk of intracerebral hemorrhage (ICH). We report the
      clinical, imaging and prognostic data of 17 patients with focal SAH revealed by
      short episodes of paresthesias mimicking transient ischemic attacks. METHODS: The
      medical records and imaging data of patients with focal acute SAH at the cerebral
      convexity and at least one episode of focal paresthesia having attended the
      Neurology Department of Caen University Hospital in the last 10 years were
      retrospectively reviewed. Hemorrhagic lesions, ischemic lesions, cerebral
      microbleeds (CMBs), superficial siderosis, white matter changes (leukoaraiosis)
      and modified Boston criteria for cerebral amyloid angiopathy (CAA) were assessed.
      All patients or relatives were contacted after a median delay of 16 months in
      order to seek for new events (death, stroke, recurrent focal symptoms, ICH and
      dementia) that occurred since hospital discharge. RESULTS: Seventeen patients (12
      men) aged 69-96 years were identified. All but 1 had multiple, repeated,
      stereotyped and brief attacks of paresthesias, associated in some of them with
      motor and/or speech difficulties, but only 1 had a headache. SAHs were seen on CT
      scans in 15/17 patients and on T2* gradient-echo magnetic resonance imaging (MRI)
      in all patients. They were multiple SAHs in 14/17 patients, including at least 1
      SAH in the central or pre- or postcentral sulcus contralateral to the symptoms in
      all patients. Five patients had punctate cortical hyperintensities on diffusion
      weighted MRI. Eleven patients had CMBs, and 4 of them had more than 5 CMBs. Seven
      patients met the modified Boston criteria for probable and 10 for possible CAA.
      At follow-up, 5 patients had a subsequent ICH, 4 of whom had received
      antithrombotic treatments. Five patients died (1 from ICH). Six patients
      developed dementia. CONCLUSION: The combination of transient, repeated and
      stereotyped attacks of unilateral paresthesias with a contralateral sulcal SAH
      seems to preferentially occur in elderly people and is often indicative of CAA.

PMID- 24029732
TI  - Worms from the Arctic are better adapted to freezing and high salinity than worms
      from temperate regions: oxidative stress responses in Enchytraeus albidus.
AB  - Enchytraeus albidus is a freeze-tolerant enchytraeid found in diverse habitats,
      from supra-littoral to terrestrial, and spanning temperate to arctic regions.
      Thus, this worm is often exposed to sub-zero temperatures and fluctuating
      salinity regimes that can lead to physiological stress. We therefore studied the
      oxidative stress by measuring lipid peroxidation, anti-oxidant defenses and
      neurotransmission activity in E. albidus from arctic (Greenland) and temperate
      (Germany) regions during a short-term exposure to saline conditions (0, 15, 35
      and 500/00 NaCl) and low temperatures (+2, -2 and -5  degrees C). Various
      enzymatic and non-enzymatic oxidative stress markers were analyzed. Results have
      shown that both salt and freezing caused oxidative stress in E. albidus,
      particularly from Germany, as confirmed by catalase, glutathione-S-transferase
      and superoxide dismutase activities and lipid peroxidation levels.
      Neurotransmission (as judged from acetylcholinesterase activity) was reduced by
      saline conditions at +2  degrees C, but stimulated at -2 and -5  degrees C. Worms
      from Greenland had relatively higher and more stable levels of antioxidants than
      worms from Germany, reflecting their higher tolerance of freezing and saline
      conditions.

PMID- 24029733
TI  - Conversion of ICRP male reference phantom to polygon-surface phantom.
AB  - The International Commission on Radiological Protection (ICRP) reference
      phantoms, developed based on computed tomography images of human bodies, provide
      much more realism of human anatomy than the previously used MIRD5 (Medical
      Internal Radiation Dose) mathematical phantoms. It has been, however, realized
      that the ICRP reference phantoms have some critical limitations showing a
      considerable amount of holes for the skin and wall organs mainly due to the
      nature of voxels of which the phantoms are made, especially due to their low
      voxel resolutions. To address this problem, we are planning to develop the
      polygon-surface version of ICRP reference phantoms by directly converting the
      ICRP reference phantoms (voxel phantoms) to polygon-surface phantoms. The
      objective of this preliminary study is to see if it is indeed possible to
      construct the high-quality polygon-surface phantoms based on the ICRP reference
      phantoms maintaining identical organ morphology and also to identify any
      potential issues, and technologies to address these issues, in advance. For this
      purpose, in the present study, the ICRP reference male phantom was roughly
      converted to a polygon-surface phantom. Then, the constructed phantom was
      implemented in Geant4, Monte Carlo particle transport code, for dose
      calculations, and the calculated dose values were compared with those of the
      original ICRP reference phantom to see how much the calculated dose values are
      sensitive to the accuracy of the conversion process. The results of the present
      study show that it is certainly possible to convert the ICRP reference phantoms
      to surface phantoms with enough accuracy. In spite of using relatively less
      resources (<2 man-months), we were able to construct the polygon-surface phantom
      with the organ masses perfectly matching the ICRP reference values. The analysis
      of the calculated dose values also implies that the dose values are indeed not
      very sensitive to the detailed morphology of the organ models in the phantom for
      highly penetrating radiations such as photons and neutrons. The results of the
      electron beams, on the other hand, show that the dose values of the polygon
      surface phantom are higher by a factor of 2-5 times than those of the ICRP
      reference phantom for the skin and wall organs which have large holes due to low
      voxel resolution. The results demonstrate that the ICRP reference phantom could
      provide significantly unreasonable dose values to thin or wall organs especially
      for weakly penetrating radiations. Therefore, when compared to the original ICRP
      reference phantoms, it is believed that the polygon-surface version of ICRP
      reference phantoms properly developed will not only provide the same or similar
      dose values (say, difference <5 or 10%) for highly penetrating radiations, but
      also provide correct dose values for the weakly penetrating radiations such as
      electrons and other charged particles. 

PMID- 24029734
TI  - High throughput sequencing methods and analysis for microbiome research.
AB  - High-throughput sequencing technology is rapidly improving in quality, speed and
      cost. It is therefore becoming more widely used to study whole communities of
      prokaryotes in many niches. This review discusses these techniques, including
      nucleic acid extraction from different environments, sample preparation and high
      throughput sequencing platforms. We also discuss commonly used and recently
      developed bioinformatic tools applied to microbiomes, including analyzing
      amplicon sequences, metagenome shotgun sequences and metatranscriptome sequences.
      This field is relatively new and rapidly evolving, thus we hope that this review
      will provide a baseline for understanding these methods of microbiome analyses.
      Additionally, we seek to stimulate others to solve the many problems that still
      exist with the sensitivity, specificity and interpretation of high throughput
      microbiome sequence analysis. 

PMID- 24029735
TI  - Changes in bone mineral density over a 2-year period in HIV-1-infected men under
      combined antiretroviral therapy with osteopenia.
AB  - OBJECTIVE: Although osteopenia is common in HIV-infected patients, there is by
      now limited data on the evolution of bone mineral density in this population. We
      aimed to evaluate the course of osteopenia over a 2-year period in HIV-1-infected
      men, and to identify risk factors for abnormal bone mineral density (BMD)
      decline. METHODS: HIV-1-infected men on combined antiretroviral therapy (cART)
      screened in the ANRS 120 Fosivir trial, diagnosed with low BMD (-2.5 <=T-score <
      1), not receiving antiosteoporotic agents, with sequential dual-energy-X ray
      absorptiometry (DXA) available at baseline were eligible for this study and had a
      second DXA performed between months 24 and 36. RESULTS: We enrolled 94 men with a
      median age of 46 years [interquartile range (IQR), 41-53], BMI 22 kg/m2 (21-25)
      and a CD4 cell nadir of 164/MUl (69-261). They were receiving cART for a median
      of 7.5 years (5.8-9.5). Over a median interval of 2.6 years (2.3-2.9) between the
      two DXA tests, the mean change in BMD was -0.5 +/- 1.7% per year (P = 0.010) at
      the lumbar spine and -0.4 +/- 1.8% per year (P = 0.033) at the hip. BMD fell by
      more than the smallest detectable difference (SDD) in, respectively, 25.5 and
      27.7% of patients at the lumbar spine and hip. Tenofovir (TDF) exposure was
      independently associated with a larger decline in BMD at both sites [lumbar
      spine, OR = 2.4 (1.2-4.9); hip, OR = 2.8 (1.3-5.9)]. CONCLUSION: Although
      osteopenia overall modestly changes over 2 years in long-term cART-treated
      patients, a quarter of patients experienced a significant loss (>1 SDD)
      associated with TDF exposure.

PMID- 24029736
TI  - Antiviral treatments over cell-to-cell infection: is it just a matter of dose?

PMID- 24029737
TI  - Generalizability and scalability of HIV 'treatment as prevention'.

PMID- 24029738
TI  - Have the explosive HIV epidemics in sub-Saharan Africa been driven by higher
      community viral load?

PMID- 24029739
TI  - Have the explosive HIV epidemics in Sub-Saharan Africa been driven by higher
      community viral load?

PMID- 24029740
TI  - Evaluating the use of pairwise dissimilarity metrics in paleoanthropology.
AB  - Questions of alpha taxonomy are best addressed by comparing unknown specimens to
      samples of the taxa to which they might belong. However, analysis of the hominin
      fossil record is riddled with methods that claim to evaluate whether pairs of
      individual fossils belong to the same species. Two such methods, log sem and the
      related STET method, have been introduced and used in studies of fossil hominins.
      Both methods attempt to quantify morphological dissimilarity for a pair of
      fossils and then evaluate a null hypothesis of conspecificity using the
      assumption that pairs of fossils that fall beneath a predefined dissimilarity
      threshold are likely to belong to the same species, whereas pairs of fossils
      above that threshold are likely to belong to different species. In this
      contribution, we address (1) whether these particular methods do what they claim
      to do, and (2) whether such approaches can ever reliably address the question of
      conspecificity. We show that log sem and STET do not reliably measure deviations
      from shape similarity, and that values of these measures for any pair of fossils
      are highly dependent upon the number of variables compared. To address these
      issues we develop a measure of shape dissimilarity, the Standard Deviation of
      Logged Ratios (sLR). We suggest that while pairwise dissimilarity metrics that
      accurately measure deviations from isometry (e.g., sLR) may be useful for
      addressing some questions that relate to morphological variation, no pairwise
      method can reliably answer the question of whether two fossils are conspecific. 

PMID- 24029741
TI  - Primary biliary cirrhosis: is there still a place for histological evaluation?

PMID- 24029744
TI  - Targeting protease activated receptor-1 with P1pal-12 limits bleomycin-induced
      pulmonary fibrosis.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis is the most devastating fibrotic
      diffuse parenchymal lung disease which remains refractory to pharmacological
      therapies. Therefore, novel treatments are urgently required. Protease-activated
      receptor (PAR)-1 is a G-protein-coupled receptor that mediates critical
      signalling pathways in pathology and physiology. Bleomycin-induced lung fibrosis
      has been shown to be diminished in PAR-1-deficient mice. The purpose of this
      study is to investigate whether pharmacological PAR-1 inhibition is a potential
      therapeutic option to combat pulmonary fibrosis. METHODS: Pulmonary fibrosis was
      induced by intranasal instillation of bleomycin into wild-type mice with or
      without a specific PAR-1 antagonist (ie, P1pal-12, a pepducin that blocks the PAR
      1/G-protein interaction). Fibrosis was assessed by hydroxyproline analysis,
      immunohistochemistry, quantitative PCR and western blot for fibrotic markers
      expression. RESULTS: We first show that P1pal-12 effectively inhibits PAR-1
      induced profibrotic responses in fibroblasts. Next, we show that once daily
      treatment with 0.5, 2.5 or 10 mg/kg P1pal-12 reduced the severity and extent of
      fibrotic lesions in a dose-dependent manner. These findings correlated with
      significant decreases in fibronectin, collagen and alpha smooth muscle actin
      expression at the mRNA and protein level in treated mice. To further establish
      the potential clinical applicability of PAR-1 inhibition, we analysed fibrosis in
      mice treated with P1pal-12 1 or 7 days after bleomycin instillation.
      Interestingly, when administered 7 days after the induction of fibrosis, P1pal-12
      was as effective in limiting the development of pulmonary fibrosis as when
      administration was started before bleomycin instillation. CONCLUSIONS: Overall,
      targeting PAR-1 may be a promising treatment for pulmonary fibrosis.

PMID- 24029743
TI  - Design of the Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS).
AB  - Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a
      multicentre observational study of chronic obstructive pulmonary disease (COPD)
      designed to guide future development of therapies for COPD by providing robust
      criteria for subclassifying COPD participants into groups most likely to benefit
      from a given therapy during a clinical trial, and identifying
      biomarkers/phenotypes that can be used as intermediate outcomes to reliably
      predict clinical benefit during therapeutic trials. The goal is to enrol 3200
      participants in four strata. Participants undergo a baseline visit and three
      annual follow-up examinations, with quarterly telephone calls. Adjudication of
      exacerbations and mortality will be undertaken. 

PMID- 24029745
TI  - Cyclical caspofungin for chronic pulmonary aspergillosis in sarcoidosis.
AB  - In sarcoidosis, chronic pulmonary aspergillosis (CPA) may be associated with
      significant morbidity, and treatment failure rates are often high, even with
      newer triazole antifungal agents. We report a treatment regimen of cyclical
      caspofungin infusions in 10 patients with sarcoidosis and worsening CPA despite
      oral triazoles. 

PMID- 24029746
TI  - In vivo and in vitro effects of secondary metabolites against Xanthomonas
      campestris pv. campestris.
AB  - Brassica rapa is a crucifer that is grown worldwide, mainly as a vegetable. The
      quality of B. rapa crops is highly affected by the disease caused by the bacteria
      Xanthomonas campestris pv. campestris (Xcc). Glucosinolates and phenolic
      compounds can confer resistance to Brassica crops against pests and diseases, but
      few works have been done to evaluate their role in Xcc resistance. The objectives
      of this work were: (1) to evaluate the in vivo and in vitro antibacterial effect
      of gluconapin, its isothiocyanate and the methanolic extracts of B. rapa against
      the type 4 of Xcc, and (2) to test if there is induced resistance mediated by
      glucosinolates or phenolic compounds in two varieties of B. rapa. Gluconapin and
      its ITC varieties had an antibacterial effect on the development of Xanthomonas
      and this effect was strongly dependent on the concentration applied. Methanolic
      extracts from B. rapa, containing glucosinolates and phenolic compounds,
      inhibited the growth of these bacteria. Concentration of gluconapin is higher in
      resistant plants than in the susceptible ones and there is an induction of
      gluconapin, some flavonoids and sinapic acid 48 to 72 h after inoculation.
      Gluconapin plays a role in the constitutive resistance to Xcc, while gluconapin,
      some flavonoids and hydroxycinnamic acids are induced by a Xcc infection but it
      is not clear if this induction confers resistance to this disease. 

PMID- 24029747
TI  - An efficient synthesis of enantiopure (R)-heteroarylpyrimidine analogs.
AB  - An efficient synthesis of enantiopure (R)-heteroarylpyrimidine analogs is
      described here, which involves introduction of a chiral group, formation and
      separation of diasteroisomers and final transformation of an amide to an ester.
      The absolute configuration of the enantiopure HAPs is confirmed by X-ray analysis
      of their intermediates. 

PMID- 24029749
TI  - Abstracts of the 2013 Annual Meeting of the Society for Technology in Anesthesia
      (STA). January 9-12, 2013. Scottsdale, Arizona, USA.

PMID- 24029748
TI  - Metal complexes of quinolone antibiotics and their applications: an update.
AB  - Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and
      excellent bioavailability. Due to the chemical functions found on their nucleus
      (a carboxylic acid function at the 3-position, and in most cases a basic
      piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl
      oxygen atom at the 4-position) quinolones bind metal ions forming complexes in
      which they can act as bidentate, as unidentate and as bridging ligand,
      respectively. In the polymeric complexes in solid state, multiple modes of
      coordination are simultaneously possible. In strongly acidic conditions,
      quinolone molecules possessing a basic side nucleus are protonated and appear as
      cations in the ionic complexes. Interaction with metal ions has some important
      consequences for the solubility, pharmacokinetics and bioavailability of
      quinolones, and is also involved in the mechanism of action of these bactericidal
      agents. Many metal complexes with equal or enhanced antimicrobial activity
      compared to the parent quinolones were obtained. New strategies in the design of
      metal complexes of quinolones have led to compounds with anticancer activity.
      Analytical applications of complexation with metal ions were oriented toward two
      main directions: determination of quinolones based on complexation with metal
      ions or, reversely, determination of metal ions based on complexation with
      quinolones. 

PMID- 24029750
TI  - Aplastic anemia secondary to azathioprine in systemic lupus erythematosus: report
      of a case with normal thiopurine S-methyltransferase enzyme activity and review
      of the literature.
AB  - Azathioprine-induced aplastic anemia and fatal myelosuppression is a rare
      occurrence in patients with systemic lupus erythematosus (SLE). We report a case
      of a 53-year-old female with a normal thiopurine S-methyltransferase (TPMT) level
      who developed aplastic anemia within 4 weeks of azathioprine initiation,
      resulting in death. Physicians should be vigilant in monitoring routine blood
      work when administering azathioprine, a relatively common drug, in patients with
      SLE. 

PMID- 24029751
TI  - Review and perspectives on pharmacological vitreolysis.
AB  - The vitreous is involved in multiple diseases when an incomplete posterior
      vitreous detachment (PVD) occurs. An incomplete PVD can lead to several
      pathological conditions. Such visually threatening conditions are traditionally
      of exclusive surgical interest. In contrast, pharmacological vitreolysis is the
      effort to reduce or eliminate the pathogenetic role of the vitreous solely by
      means of drug delivery. Here we aim to review and summarize the evidence
      available to date about this challenging new approach.

PMID- 24029752
TI  - Design parameters for voltage-controllable directed assembly of single
      nanoparticles.
AB  - Techniques to reliably pick-and-place single nanoparticles into functional
      assemblies are required to incorporate exotic nanoparticles into standard
      electronic circuits. In this paper we explore the use of electric fields to drive
      and direct the assembly process, which has the advantage of being able to control
      the nano-assembly process at the single nanoparticle level. To achieve this, we
      design an electrostatic gating system, thus enabling a voltage-controllable
      nanoparticle picking technique. Simulating this system with the nonlinear Poisson
      Boltzmann equation, we can successfully characterize the parameters required for
      single particle placement, the key being single particle selectivity, in effect
      designing a system that can achieve this controllably. We then present the
      optimum design parameters required for successful single nanoparticle placement
      at ambient temperature, an important requirement for nanomanufacturing processes.

PMID- 24029753
TI  - Complete Genome Sequence of SfII, a Serotype-Converting Bacteriophage of the
      Highly Prevalent Shigella flexneri Serotype 2a.
AB  - SfII is a serotype-converting temperate bacteriophage of the highly prevalent
      Shigella flexneri serotype 2a. We isolated the SfII phage from a wild-type strain
      of S. flexneri serotype 2a. Here, we present the complete genome sequence of this
      phage. 

PMID- 24029754
TI  - Genome Sequence of the Melanin-Producing Extremophile Aeromonas salmonicida
      subsp. pectinolytica Strain 34melT.
AB  - The genome of Aeromonas salmonicida subsp. pectinolytica strain 34mel(T),
      isolated from a heavily polluted river, contains several genomic islands and
      putative virulence genes. The identification of genes involved in resistance to
      different kinds of stress sheds light on the mechanisms used by this strain to
      thrive in an extreme environment. 

PMID- 24029755
TI  - Draft Genome Sequence of the Cellulolytic Bacterium Clostridium papyrosolvens C7
      (ATCC 700395).
AB  - We report the draft genome sequence of the cellulose-degrading bacterium
      Clostridium papyrosolvens C7, originally isolated from mud collected below a
      freshwater pond in Massachusetts. This Gram-positive bacterium grows in a
      mesophilic anaerobic environment with filter paper as the only carbon source, and
      it has a simple cellulosome system with multiple carbohydrate-degrading enzymes. 

PMID- 24029756
TI  - Draft Genome Sequence of Thermoanaerobacter sp. Strain A7A, Reconstructed from a
      Metagenome Obtained from a High-Temperature Hydrocarbon Reservoir in the Bass
      Strait, Australia.
AB  - The draft genome sequence of Thermoanaerobacter sp. strain A7A was reconstructed
      from a metagenome of a microbial consortium obtained from the Tuna oil field in
      the Gippsland Basin, Australia. The organism is a strict anaerobe that is
      predicted to ferment a range of simple sugars and undertake sulfur reduction. 

PMID- 24029757
TI  - Complete Genome Sequence of Staphylococcus aureus Tager 104, a Sequence Type 49
      Ancestor.
AB  - We report here the complete genome sequence of Staphylococcus aureus Tager 104,
      originally isolated from a cutaneous abscess in 1947 by Morris Tager. Sequence
      typing of the strain revealed its membership in sequence type 49 (ST49), a
      previously unknown multilocus sequence type (MLST) in clinical samples. 

PMID- 24029758
TI  - Draft Genome Sequence of Bacillus pumilus CCMA-560, Isolated from an Oil
      Contaminated Mangrove Swamp.
AB  - Bacillus pumilus strain CCMA-560 was isolated from an oil-contaminated mangrove
      swamp and was shown to produce biosurfactants. The strain appears to be capable
      of degrading some plant cell wall-related compounds, including hemicelluose and
      pectin. Genes for biopolymer export and polysaccharide intercellular adhesin
      synthesis were also annotated. 

PMID- 24029759
TI  - Draft Genome Sequence of Ammonia-Producing Aeromonas sp. MDS8 Strain MCC2167 from
      Sludge of a Dairy Effluent Treatment Plant.
AB  - The draft genome sequence of an amylase-, protease-, lipase-, oxidase-, and
      catalase-producing Gram-negative bacillus (Aeromonas sp. MDS8 strain MCC2167)
      with the ability to produce ammonia during 16 h of growth at 37 degrees C,
      isolated from dairy sludge, with a size of 4,841,753 bp and a G+C content of
      63.1%, is reported here. 

PMID- 24029760
TI  - Chromosome Sequence of Borrelia miyamotoi, an Uncultivable Tick-Borne Agent of
      Human Infection.
AB  - Borrelia miyamotoi is a newly recognized agent of human disease. B. miyamotoi
      strain LB-2001, an isolate from the tick Ixodes scapularis, was propagated in
      mice. The sequence of the chromosome was determined by next-generation sequencing
      of DNA isolated from whole blood. The sequence established that B. miyamotoi is a
      relapsing fever group species. 

PMID- 24029761
TI  - Genome Sequence of Novosphingobium lindaniclasticum LE124T, Isolated from a
      Hexachlorocyclohexane Dumpsite.
AB  - Novosphingobium lindaniclasticum LE124(T) is a hexachlorocyclohexane (HCH)
      degrading bacterium isolated from a high-dosage-point HCH dumpsite (450 mg HCH/g
      soil) located in Lucknow, India (27 degrees 00'N and 81 degrees 09'E). Here, we
      present the annotated draft genome sequence of strain LE124(T), which has an
      estimated size of 4.86 Mb and is comprised of 4,566 coding sequences. 

PMID- 24029762
TI  - Genome Sequence of the Bacterium Bifidobacterium longum Strain CMCC P0001, a
      Probiotic Strain Used for Treating Gastrointestinal Disease.
AB  - Bifidobacterium longum subsp. longum CMCC P0001, a standard probiotic strain in
      China, has been widely used in clinical medicine for more than 20 years. Here we
      report the genome features of B. longum strain CMCC P0001. 

PMID- 24029763
TI  - Draft Genome Sequence of Sphingobium quisquiliarum Strain P25T, a Novel
      Hexachlorocyclohexane (HCH)-Degrading Bacterium Isolated from an HCH Dumpsite.
AB  - Here, we report the draft genome sequence (4.2 Mb) of Sphingobium quisquiliarum
      strain P25(T), a natural lin (genes involved in degradation of
      hexachlorocyclohexane [HCH] isomers) variant genotype, isolated from a heavily
      contaminated (450 mg HCH/g of soil) HCH dumpsite. 

PMID- 24029764
TI  - Complete Genomic Sequence of "Thermofilum adornatus" Strain 1910bT, a
      Hyperthermophilic Anaerobic Organotrophic Crenarchaeon.
AB  - The complete genomic sequence of a novel hyperthermophilic crenarchaeon, strain
      1910b(T), was determined. The genome comprises a 1,750,259-bp circular chromosome
      containing single copies of 3 rRNA genes, 43 tRNA genes, and 1,896 protein-coding
      sequences. In silico genome-genome hybridization suggests the proposal of a novel
      species, "Thermofilum adornatus" strain 1910b(T). 

PMID- 24029765
TI  - Complete genome sequences of two bovine viral diarrhea viruses isolated from
      brain tissues of nonambulatory (downer) cattle.
AB  - Here, we report the complete genome sequences of two bovine viral diarrhea
      viruses (BVDVs) (strains 11F011 and 12F004) isolated from brain tissues from
      nonambulatory (downer) cattle. The complete genomes of strains 11F011 and 12F004
      contain 12,287 nucleotides (nt) with a single large open reading frame and 12,301
      nt with a single large open reading frame, respectively. Phylogenetic analysis
      indicated that these strains belong to the BVDV-2a and -1b genotypes,
      respectively. 

PMID- 24029766
TI  - First Insights into the Genome of the Gram-Negative, Endospore-Forming Organism
      Sporomusa ovata Strain H1 DSM 2662.
AB  - The genome of Sporomusa ovata strain H1 DSM 2662, an anaerobic, Gram-negative
      endospore-forming bacterium, was sequenced. S. ovata uses N-methyl compounds,
      primary alcohols, fatty acids, and H2 and CO2 as energy and carbon sources to
      produce acetate. The genome harbors one chromosome, which encodes proteins
      typical for sporulation. 

PMID- 24029767
TI  - Draft Genome Sequence of Entomopathogenic Bacterium Photorhabdus temperata Strain
      M1021, Isolated from Nematodes.
AB  - Photorhabdus temperata strain M1021 is an entomopathogenic bacterium belonging to
      the family Enterobacteriaceae and is symbiotically associated with nematodes. The
      draft genome sequence of P. temperata strain M1021 consists of 5,598,253 bp with
      a G+C content of 43.7%, and it has 6,120 protein-coding genes. 

PMID- 24029776
TI  - Urothelial differentiation of human umbilical cord-derived mesenchymal stromal
      cells in vitro.
AB  - Human umbilical cord-derived mesenchymal stromal cells (hUCMSCs) are the most
      primitive of those isolated from other post-natal tissue source. The hUCMSCs
      possess the capability of differentiating along multi-lineage. This study aimed
      to investigate whether hUCMSCs can differentiate into urothelium-like cells. The
      hUCMSCs were isolated from fresh human umbilical cord postpartum and expanded at
      least to passage 3 in vitro. Subsequently, they were cultured with conditioned
      medium from urothelial cells (UC-CM) supplemented with 20 ng/ml exogenous
      epidermal growth factor (EGF). Urothelial cell specific marker uroplakin II
      (UPII) and cytokeratins were evaluated by reverse transcriptase-polymerase chain
      reaction (RT-PCR) and immunofluorescence technology. During culture, hUCMSCs
      started to express UPII and cytokeratins weakly at 7 days and were significantly
      up-regulated at 2 weeks post-induction. Additionally, morphology of hUCMSCs
      changed from spindle-shape to a polygonal epithelial-shape similar to that of
      urothelial cells after 7 days. The study results indicated that hUCMSCs can
      differentiate into urothelium-like cells in a defined micro-environment in vitro
      constituted by UC-CM and exogenous EGF. 

PMID- 24029777
TI  - A retrospective study of gemcitabine and cisplatin combination therapy as second
      line treatment for advanced biliary tract cancer.
AB  - BACKGROUND: To evaluate the treatment outcome of gemcitabine and cisplatin
      combination therapy as second-line treatment for advanced biliary tract cancer.
      PATIENTS AND METHODS: Patients with advanced biliary tract cancer who were
      refractory to gemcitabine-based first-line chemotherapy were treated with
      gemcitabine and cisplatin combination therapy. Gemcitabine (1,000 mg/m(2)) and
      cisplatin (25 mg/m(2)) were administered intravenously on days 1 and 8, repeated
      every 3 weeks. RESULTS: Sixty patients were included. The tumor response and
      disease control rates were 1.7 and 58.3%, respectively. The median overall
      survival and time to progression were 6.7 months (95% CI 4.9-8.1) and 3.5 months
      (95% CI 2.5-5.0), respectively. Grade 3/4 toxicities included leucopenia (20%),
      neutropenia (25%), anemia (23%), thrombocytopenia (17%), nausea (2%), anorexia
      (2%), and liver dysfunction (2%). CONCLUSIONS: Gemcitabine and cisplatin
      combination therapy showed moderate efficacy and safety as second-line treatment
      for advanced biliary tract cancer that is refractory to gemcitabine-based first
      line chemotherapy.

PMID- 24029779
TI  - Enhanced power output of an electrospun PVDF/MWCNTs-based nanogenerator by tuning
      its conductivity.
AB  - PVDF nanofibre-based piezoelectric nanogenerators are directly prepared via
      electrospinning without any post-poling treatment. The effect of the addition of
      multi-walled carbon nanotubes (MWCNTs) on the fibre diameter, mechanical
      properties, beta-phase composition, surface and volume conductivities, output
      voltage and output power are investigated. Increased surface conductivity of the
      poly-vinylidene fluoride (PVDF) nanofibre mats, which plays an important role in
      the enhancement of output power, is first found by the addition of an appropriate
      amount of MWCNTs. The maximum generated piezo-voltage exhibited by PVDF nanofibre
      mats in the presence of 5 wt% MWCNTs is as high as 6 V, while the average
      capacitor charging power is 81.8 nW, increases of 200% and 44.8%, respectively,
      compared with bare PVDF nanofibre mats.

PMID- 24029778
TI  - The role of oxidants and reactive nitrogen species in irritable bowel syndrome: a
      potential etiological explanation.
AB  - BACKGROUND: The aim of this study was to evaluate the plasma concentrations of
      malondialdehyde (MDA) and nitric oxide (NO) and the plasma activities of oxidant
      and antioxidant enzymes in patients with IBS. MATERIAL/METHODS: A total of 36
      patients with IBS were included in the study. Thirty-five healthy subjects were
      selected to form the control group. Superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GSH-Px), xanthine oxidase (XO), adenosine deaminase (AD)
      activities, and malondialdehyde (MDA) and nitric oxide (NO) concentrations were
      studied in the serum samples of all patients and controls. RESULTS: Plasma XO and
      AD activities, and MDA and NO concentrations were significantly higher in IBS
      patients than in controls. The SOD, CAT, and GSH-Px activities in the serum of
      patients with IBS were significantly lower than that of controls. CONCLUSIONS:
      These results suggest that lipid peroxidation and alterations in the oxidant
      antioxidant enzymatic system may play a role in the pathogenesis of IBS.
      Increased lipid peroxidation in IBS may be related to an increase in NO level and
      XO activity and a decrease in antioxidant enzymes activities. In addition,
      increased AD activity may have a role in immunological changes of IBS patients.

PMID- 24029780
TI  - Risk of stroke with thiazolidinediones: a ten-year nationwide population-based
      cohort study.
AB  - BACKGROUND: Thiazolidinediones (TZDs) - rosiglitazone and pioglitazone - a class
      of insulin sensitizer for treating type 2 diabetes, have been reported to exhibit
      neuroprotective effects in preclinical studies and have good effects in the
      control of blood sugar for diabetic patients with insulin resistance. However,
      clinical trials and observational studies have raised the possibility of higher
      stroke risk in patients treated with rosiglitazone. Whether pioglitazone poses
      similar stroke risk remains uncertain. Most of the studies on cardiovascular
      effects of TZDs were based on studies in the USA and Europe. The present study
      aimed to compare the stroke risk among diabetic patients on TZD to those on non
      TZD medications in an Asian population. METHODS: The study cohort included 15,981
      patients with a diagnosis of diabetes without prior stroke, acute myocardial
      infarction (AMI) or heart failure who were followed from 2001 to 2010. Patients
      were classified by their prescriptions into rosiglitazone, pioglitazone and non
      TZD groups. The study end points included ischemic and hemorrhagic stroke. In
      view of the reported association of heart failure and AMI with rosiglitazone,
      these 2 end points were also included in the present study. Cox hazard
      proportional models were used to estimate the risk of developing the end points.
      Likelihood ratio test was used to examine the age-drug interactions. Dose
      response effects were evaluated by comparing the incidence rates among patients
      with different cumulative exposures to TZD. RESULTS: During the 10-year follow
      up, the rosiglitazone group showed significantly higher risk of ischemic stroke
      (multivariate adjusted hazard ratio, HR = 1.39; 95% confidence interval, CI =
      1.16-1.66) and heart failure (HR = 1.59; 95% CI = 1.18-2.14) than the non-TZD
      group. The pioglitazone group did not show significant difference from the non
      TZD group in ischemic stroke (HR = 0.97; 95% CI = 0.75-1.26) and heart failure
      (HR = 0.94; 95% CI = 0.59-1.50). The results also showed a significant dose
      dependent effect of higher risk of ischemic stroke with increasing dosage of
      rosiglitazone, while there was no increased risk at any level of pioglitazone
      dosage. CONCLUSIONS: This population-based cohort study shows that rosiglitazone
      imposes a higher risk of developing stroke or heart failure in this Asian patient
      population, suggesting the adverse side effects of rosiglitazone across ethnic
      boundaries. Pioglitazone, on the other hand, does not increase cardiovascular or
      stroke risk compared to the non-TZD group among diabetic patients without a
      history of macrovascular disease.

PMID- 24029781
TI  - Importance of systematic reviews and meta-analyses in pediatric nutrition.
AB  - To address information overload, systematic methods have been developed to
      identify, assess, and synthesize information. This chapter provides an overview
      of the basic principles of systematic review and meta-analysis of randomized
      controlled trials, which are considered to be the best study design for answering
      questions about the effectiveness of an intervention. It also discusses the
      problems and limitations of using a meta-analytical approach. As the number of
      systematic reviews and meta-analyses is increasing rapidly, also in the field of
      pediatric nutrition, it is essential that the strengths as well as the
      limitations and caveats of this approach are well understood. 

PMID- 24029782
TI  - Strengths and weaknesses of observational nutritional studies.
AB  - Observational studies, which are often performed, play a meaningful role in
      nutritional research. They provide the best answers to questions regarding
      prevalence, prognosis, diagnosis, and treatment harms. Moreover, they generate
      hypotheses and prompt further, adequately designed research. However, despite
      their many advantages, observational nutritional studies have important
      limitations. These are factors that are strictly bound to the specific study
      design, nutrition-related, or performance-quality dependent. Potential advantages
      and disadvantages determine each study's strengths and weaknesses. Thus,
      knowledge of these advantages and disadvantages is crucial for proper planning,
      satisfactory study performance, and reasonable interpretation of the results. 

PMID- 24029783
TI  - Scientific standards for human intervention trials evaluating health benefits of
      foods, and their application to infants, children and adolescents.
AB  - Associations between the consumption of particular foods and health outcomes may
      be indicated by observational studies. However, intervention trials that evaluate
      the health benefits of foods provide the strongest evidence to support dietary
      recommendations for health. Thus, it is important that these trials are carried
      out safely, and to high scientific standards. Accepted standards for the
      reporting of the health benefits of pharmaceutical and other medical
      interventions have been provided by the Consolidated Standards of Reporting
      Trials (CONSORT) statement. However, there are no generally accepted standards
      for trials to evaluate the health benefits of foods. Trials with foods differ
      from medical trials in issues related to safety, ethics, research governance and
      practical implementation. Furthermore, these important issues can deter the
      conduct of both medical and nutrition trials in infants, children and
      adolescents. This paper provides standards for the planning, design, conduct,
      statistical analysis and interpretation of human intervention trials to evaluate
      the health benefits of foods that are based on the CONSORT guidelines, and
      outlines the key issues that need to be addressed in trials in participants in
      the paediatric age range. 

PMID- 24029784
TI  - Early nutrition and health: short- and long-term outcomes.
AB  - Maternal diet, nutritional status during pregnancy, and the early diet of the
      offspring play an important role in later health. The short- and long-term
      outcomes of early nutrition have been extensively studied in recent decades. One
      of the most commonly investigated nutritional interventions is breastfeeding,
      which is associated with a number of positive short- and long-term outcomes. A
      short-term effect of breastfeeding is reduced morbidity and mortality in children
      from poor living conditions and in preterm infants. Breastfeeding is associated
      with better cognitive development and also has a long-term protective effect on
      obesity risk, prevalence of type 2 diabetes, and a lowering effect on blood
      pressure. Selected nutrients have undergone extensive investigation to show their
      role in disease prevention or improved development, e.g. protein intake in
      infancy seems to be associated with a later risk of obesity or docosahexaenoic
      acid supplementation has a positive impact on cognitive function. Another
      consideration is the fast catch-up growth in small for gestational age infants as
      an important factor associated with adult risk of cardiovascular problems. On the
      other hand, high protein and energy intake seems to be positively associated with
      some indicators of cognitive development. Most of the evidence comes from
      observational studies that cannot exclude potential confounders. Animal studies
      demonstrate causality but should not be directly extrapolated to humans. The
      number of randomized controlled studies is increasing but long-term follow-ups
      are necessary to obtain convincing results. The majority of these trials compare
      different infant formula compositions and macro- or micronutrient
      supplementation. One of the major questions is to define a critical (or
      opportunity) window and a mechanism of nutritional influence on several health
      outcomes. 

PMID- 24029785
TI  - Probiotics, prebiotics, and dietary fiber in the management of functional
      gastrointestinal disorders.
AB  - At best, currently available therapies provide symptomatic relief from functional
      gastrointestinal disorders (FGD). No existing therapy, however, can influence the
      natural course of any of these disorders, prompting interest in new and safe
      treatment options. This paper summarizes the clinical evidence from randomized
      controlled trials (RCTs) and their meta-analyses of the effectiveness of
      probiotics, prebiotics, and dietary fiber in the treatment of FGD in the
      pediatric population. While it is too soon to recommend the routine use of any
      probiotics for treating FGD, some of these therapeutic options can provide a
      health benefit to patients, and therefore can be discussed with patients and/or
      caregivers. Lactobacillus reuteri DSM 17938 has consistently improved symptoms of
      infantile colic. The use of Lactobacillus GG moderately increased treatment
      success in children with abdominal pain-related FGD, particularly among children
      with irritable bowel syndrome. Also, data from one trial suggest that VSL#3 seems
      to be effective in ameliorating symptoms and improving the quality of life of
      children affected by irritable bowel syndrome. L. reuteri DSM 17938 may help
      infants with constipation. Limited evidence suggests that administration of a
      fiber supplement is more effective than placebo for the treatment of childhood
      constipation. 

PMID- 24029786
TI  - Growing-up milk: a necessity or marketing?
AB  - Growing-up milk (GUM) products intended for children between 1 and 3 years of age
      are increasingly being introduced into the diets of young children. Although not
      a necessity for adequate nutrition of that age group, they can compensate for
      nutritional deficiencies which may occur in the transition phase of infant
      nutrition to family food, particularly when bad dietary patterns prevail in the
      family. For that purpose, GUM should be composed to decrease the overall protein
      intake which tends to be higher than the reference values for that age. This can
      be achieved by diluting fat-reduced cow's milk to a protein level comparable to
      infant or follow-on formulae and by partially replacing cow's milk fat with
      appropriate vegetable oils to increase the content of essential fatty acids and
      possibly by adding long-chain polyunsaturated fatty acids, docosahexaenoic and
      arachidonic acids whilst preserving the content of some minerals (such as calcium
      and phosphorus) and vitamins (B2 and B12) well represented in cow's milk. The
      content of iron, iodine, zinc and the vitamins A and D should be the same as in a
      follow-on formula. Based on available evidence, GUM should not be promoted as a
      necessity in the nutrition of young children. 

PMID- 24029787
TI  - Cow's milk and goat's milk.
AB  - Cow's milk is increasingly suggested to play a role in the development of chronic
      degenerative, non-communicable disorders whereas goat's milk is advocated as
      having several health benefits. Cow's milk is a rich and cheap source of protein
      and calcium, and a valuable food for bone health. Despite their high content in
      saturated fats, consumption of full-fat dairy products does not seem to cause
      significant changes in cardiovascular disease risk variables. Early introduction
      of cow's milk is a strong negative determinant of iron status. Unmodified cow's
      milk does not meet nutritional requirements of infants although it is acceptable
      to add small volumes of cow's milk to complementary foods. Cow's milk protein
      allergy has a prevalence ranging from 2 to 7%, and the age of recovery is usually
      around 2-3 years. The evidence linking cow's milk intake to a later risk of type
      1 diabetes or chronic degenerative, non-communicable disorders (obesity,
      metabolic syndrome, type 2 diabetes, hypertension) is not convincing. Milk
      probably protects against colorectal cancer, diets high in calcium are a probable
      cause of prostate cancer, and there is limited evidence suggesting that high
      consumption of milk and dairy products increases the risk for prostate cancer.
      There is no evidence to support the use of a cow's milk-free diet as a primary
      treatment for individuals with autistic spectrum disorders. Unmodified goat's
      milk is not suitable for infants because of the high protein and minerals content
      and of a low folate content. Goat's milk has no clear nutritional advantage over
      cow's milk and is not less allergenic. The European Food Safety Authority
      recently stated that proteins from goat's milk can be suitable as a protein
      source for infant and follow-on formula, provided the final product complies with
      the compositional criteria laid down in Directive 2006/141/EC. 

PMID- 24029788
TI  - The timing of introduction of complementary foods and later health.
AB  - Complementary food is needed when human milk (or infant formula) alone is no
      longer sufficient for nutritional reasons. The timing of introduction needs to be
      determined on an individual basis although 6 months of exclusive breastfeeding
      can be recommended for most healthy term infants. Solid foods are intended to
      'complement' ongoing breastfeeding with those dietary items whose intake has
      become marginal or insufficient. Both breastfeeding and complementary feeding can
      have direct or later consequences on health. Possible short-term health effects
      concern growth velocity and infections while possible long-term effects may
      relate to obesity, cardiovascular disease, autoimmunity (celiac disease and type
      1 diabetes) and atopic disorders. For most of these it is impossible on the basis
      of the available evidence to conclude on the age when risks related to the start
      of complementary feeding are lowest or highest, with the possible exception of
      infections and early growth velocity. For undesirable health consequences, whilst
      potential mechanisms are recognized, the evidence from mostly observational
      studies is insufficient and requires more and prospective research. While the 6
      month goal is desirable, introduction of suitable complementary food after 4
      completed months with ongoing breastfeeding can be considered without adverse
      health consequences for infants living in affluent countries. Even less evidence
      on the consequences of the timing of complementary food introduction is available
      for formula-fed infants. 

PMID- 24029789
TI  - Dietary interventions for primary allergy prevention--what is the evidence?
AB  - Allergen exposure in the early postnatal life of an infant with a genetic
      predisposition for allergy is regarded as at least one essential risk factor for
      later development of allergic diseases. The most important allergen exposure in
      early life derives from the early nutrition of the baby. Thus, intervention based
      on the concept of reducing the allergen load in the diet is one approach for
      primary allergy prevention in children at risk. This includes breastfeeding,
      allergen-reduced diet of the pregnant and lactating mother, cow milk protein
      hydrolysate infant formulas (= hypoallergenic infant formula or HA formulas) and
      time of introduction of complementary food. Data on breastfeeding regarding
      allergy prevention are inconsistent: preventive with regard to atopic eczema and
      cow milk allergy in the first 2 years, but contradictory regarding wheezing
      beyond the first years of life. Allergen-reduced diet of the pregnant mother is
      not recommended because there is no evidence for a preventive benefit, but
      instead for unwanted effects on the child's intrauterine development. Data on a
      restrictive diet during lactation are also inconsistent. If breastfeeding is
      insufficient in the first 4-6 months, both partially and extensively hydrolyzed
      formulas have been successfully used to reduce the risk for atopic eczema, but
      not for asthma or allergic rhinitis, until school age. However, from the
      available data it is suggested that the preventive potential of a formula is not
      only dependent on the degree of hydrolyzation and the protein source, but also
      from other factors like the process of manufacturing the formula. Recommendations
      for a certain formula should therefore be based on its proven efficacy in
      controlled clinical trials. For all healthy children with and without risk for
      allergy, more recent findings support complementary food introduction in the 5th
      and 6th months--independent of the kind of milk feeding--according to the
      nutritional needs and abilities of a baby. Delayed introduction of complementary
      food beyond the 6th month is no longer recommended.

PMID- 24029790
TI  - Vitamin and mineral supplementation of term infants: are they necessary?
AB  - This chapter examines the evidence behind the need or not to routinely administer
      multivitamin and/or mineral preparations to term infants. We reviewed the
      recommended dietary allowances (RDAs) of vitamins and minerals during the first
      year of life and examined whether standard nutritional options, i.e. human milk
      or infant formulae consistent with major international guidelines, satisfy these
      requirements. We found that RDA cannot adequately be met by either human milk or
      standard formulas for most vitamins and minerals. We suggest that RDAs are widely
      overestimated. A particular emphasis is placed on vitamin D and iron, where
      supplements are needed, and on iodine and vitamin B12, where supplements may be
      needed depending upon the circumstances. 

PMID- 24029791
TI  - Enteral nutrition.
AB  - Enteral nutrition (EN) is defined as the delivery of nutrients beyond the
      oesophagus via feeding tubes, and the oral intake of dietary foods for special
      medical purposes. It should be provided in patients with at least a partially
      functioning gut, whose energy and nutrient needs cannot be met by a regular food
      intake. Further indications are when the liquid diet is used as a treatment of
      the disease, and when a feeding time in the disabled child is excessively
      prolonged. Advantages of enteral intake over parenteral nutrition are well
      recognized, however there are clinical settings such as intensive care units
      where nutritional needs can often be met only by their combination despite the
      functioning gut. For the majority of paediatric patients on EN, age-adapted
      standard polymeric formula enriched with fibres is an appropriate choice. There
      is also a wide array of different disease-adapted enteral formulations that may
      be beneficial in certain clinical conditions, however for most of them, results
      of controlled studies are either missing or do not support the claims. For the
      delivery of EN, both the stomach and intermittent feeding mode are more
      physiological; continuous mode is reserved for patients with severely diseased
      gut, postpyloric feeding is indicated in patients with the high risk of tracheal
      aspiration, and feeding over gastrostomy is preferable if the anticipated
      duration of EN is exceeding 4-6 weeks. Although EN is a well-established and
      effective feeding method, it may be poorly tolerated and associated with numerous
      complications. To minimize the risks, development of procedural protocols with
      regular quality controls and audits, and monitoring by a dedicated nutrition
      support team are recommended. 

PMID- 24029792
TI  - Celiac disease--prevention strategies through early infant nutrition.
AB  - Celiac disease (CD) is an immune-mediated disease of considerable incidence,
      which negatively influences the quality of life of affected individuals and their
      families. The only currently available treatment is a lifelong gluten-free diet.
      Possible prevention strategies for CD focus on early infant feeding practices,
      namely breastfeeding and the time and mode of gluten introduction into the
      infant's diet. A systematic review of available data suggested that the risk of
      developing CD may be decreased by breastfeeding and breastfeeding at the time of
      gluten introduction. It is not clear whether this strategy prevents the disease
      or only delays the onset of symptoms. Gluten introduction should not be done
      earlier than at 4 months of age and not later than 7 months of age since both
      early and late introduction of gluten have been shown to increase the risk of CD.
      A large randomized controlled trial is being conducted in 10 European countries
      to clarify whether breastfeeding and early gluten introduction are effective in
      preventing CD in genetically susceptible individuals. 

PMID- 24029793
TI  - Interventions for treating obesity in children.
AB  - Childhood obesity remains an important public health concern and prevention
      programmes should be the priority in order to decrease the prevalence of obesity.
      The aim of this review is to summarize the most effective types of intervention
      for treating obesity in children and adolescents. A number of identified
      strategies used to treat childhood obesity range from lifestyle approaches,
      pharmacotherapy to surgical intervention. Dietary treatment of obese children and
      adolescents should aim to ensure adequate growth and development by reducing
      excessive fat mass accumulation, avoiding loss of lean body mass, improving well
      being and self-esteem, and preventing cyclical weight regain. Management
      protocols involve behaviour modifications, family support, and lifestyle changes
      which are difficult to put into practice and may require multidisciplinary
      professional teams. The cornerstone of weight loss programmes is to achieve a
      negative energy balance. There is evidence that dietary interventions are more
      effective in achieving weight loss when combined with other strategies, such as
      increasing physical activity levels and/or psychological interventions to promote
      behavioural changes. Psychological interventions have been employed in an effort
      to achieve long-term maintenance of behavioural change. Childhood obesity
      treatments should involve a combination of lifestyle changes including strategies
      to reduce energy intake, increase physical activity, reduce sedentary activities,
      facilitate family involvement and change behaviours associated with eating and
      physical activity. However, drug therapy in obese children must not be used as
      isolated treatment but as complementary to the traditional treatments of diet,
      physical activity and lifestyle changes. Besides, surgical procedures have been
      used to treat severe morbid obesity in children and adolescents when more
      conservative treatments have proven to be inadequate. 

PMID- 24029795
TI  - Evidence-based research in pediatric nutrition. Preface.

PMID- 24029796
TI  - Patterns of initial antibiotic therapy for community-acquired pneumonia in U.S.
      hospitals, 2000 to 2009.
AB  - BACKGROUND: Although clinical guidelines for management of community-acquired
      pneumonia (CAP) in non-intensive care unit ("non-ICU") hospitalized patients have
      changed substantially over the last decade, it is unknown how treatment of this
      disease has evolved over this period. METHODS: Using data from >100 U.S.
      hospitals, we identified all adults (aged >=18 years) hospitalized for CAP
      between January 1, 2000, and June 30, 2009 ("study period"). We excluded patients
      admitted to ICU <24 hours of admission, those not starting antibiotics <24 hours
      of admission, those not receiving antibiotics for >=48 hours (if alive), and
      those with probable healthcare-associated pneumonia. We defined "initial therapy"
      as all parenteral antibiotics received <=24 hours of admission, and we examined
      changes in such therapy over the study period. The statistical significance of
      changes in initial therapy was ascertained using 2-tailed chi tests. RESULTS: We
      identified 40,392 patients who met all selection criteria. In 2000, the most
      frequently used initial regimens were levofloxacin (24.0% of all such
      admissions), ceftriaxone (9.0%), cefotaxime (7.3%), ceftriaxone plus levofloxacin
      (3.2%) and azithromycin plus cefotaxime (3.0%); in 2009, they were ceftriaxone
      plus azithromycin (18.5%), levofloxacin (12.7%), ceftriaxone (6.6%), moxifloxacin
      (4.7%) and ceftriaxone + levofloxacin (3.2%). Use of single-agent regimens
      declined between 2000 and 2009 (from 48.2%-30.0%); use of vancomycin almost
      doubled (13.1%-23.3%). All findings were statistically significant (P < 0.01).
      CONCLUSIONS: Initial antibiotic therapy for non-ICU CAP has changed substantially
      in the United States over the past decade, in line with evidence of widespread
      antibiotic resistance, evolving treatment guidelines and, most recently, quality
      improvement initiatives that tie hospital payments to guideline-based care.

PMID- 24029797
TI  - In silico analyses reveal nuclear asymmetry of spongiocytes and compact cells of
      adrenocorticotrophic hormone-independent macronodular adrenocortical hyperplasia.
AB  - BACKGROUND: Little information is available about the risk of progression of
      seemingly benign adrenocortical hyperplasias to carcinomatous conditions. Using
      in silico approaches of digitally archived tissue sections, the nuclear
      morphometric parameters were compared to assess nuclear asymmetry as an index for
      nuclear atypia. METHODS: Four groups of nuclei were used for the current study:
      spongiocytes and compact cells obtained from adrenocorticotropic hormone (ACTH)
      independent macronodular hyperplasia, which were hypothesized to be high risk for
      nuclear asymmetry, and primary pigmented nodular adrenocortical disease and
      micronodular adrenocortical hyperplasia samples were used as internal controls.
      RESULTS: Analyses reveal high nuclear irregularity index of spongiocytes and
      shape factor abnormalities of both spongiocytes and compact cells of ACTH
      independent macronodular adrenal hyperplasia compared with the other 2 groups
      (high F values and very low P values after analyses of variances), thus
      confirming the hypothesis that ACTH-independent macronodular adrenal hyperplasia
      present with subtle morphometric features of nuclear atypia. CONCLUSIONS: This
      probably puts this class of adrenocortical tumors at risk of dysplastic
      progression, and more studies are needed to test the hypothesis.

PMID- 24029798
TI  - Mood symptoms in children and adolescents with autism spectrum disorders.
AB  - Asperger Syndrome (AS) and High Functioning Autism (HFA) are psychiatric
      conditions belonging to the Autistic Spectrum Disorders (ASDs), characterized by
      social dysfunction and focused interest, in the absence of mental retardation.
      Previous reports suggest that AS/HFA may be associated with important psychiatric
      comorbidities. Among the psychiatric internalizing disorders, depression and
      anxiety are probably the most common disorders. The aim of this study is to
      evaluate the prevalence of mood disorders and identifying peculiar clinical
      features in subjects suffering from AS and HFA. 30 male patients with AS/HFA, 30
      male patients affected by Major Depression (MD) and 35 male Typically Developing
      (TD) comparison were assessed with the CDI and the CDRS-R. Participants' parents
      were invited to complete the CBCL and the P-YMRS. Moreover, the CGAS was rated by
      the clinicians. The evaluation of depressive symptoms showed that AS/HFA group
      reported higher depressive symptoms, as showed by CDI total, CBCL internalizing
      and CDRS-R total, compared to the TD group. No significant difference of
      depressive symptoms was found between the AS/HFA and the MD group, with the
      exception of CDRS-R total score. Moreover, linear regression analysis in the
      AS/HFA group between CGAS and depressive symptoms revealed that a higher level of
      depressive symptoms increased the risk of poorer global functioning. These
      results suggest that the depressive symptoms in AS/HFA patients may be associated
      with poorer global functioning, with a consequent impairment in their
      psychological profile and social adjustment, and should alert clinicians to the
      importance of assessing mood disorders in order to choose the appropriate
      treatment. 

PMID- 24029799
TI  - Prospective study on risk factors for falling in elderly persons with mild to
      moderate intellectual disabilities.
AB  - Elderly persons with intellectual disabilities (ID) are at increased risk for
      falls and fall-related injuries. Although there has been extensive research on
      risk factors for falling in the general elderly population, research on this
      topic in persons with ID is rather sparse. This is the first study to prospective
      investigate risk factors for falling among elderly persons with mild to moderate
      ID. Seventy-eight ambulatory persons with mild to moderate ID (mean age 62.8 +/-
      7.6 years; 44 (56%) men; 34 (44%) mild ID) participated in this study. This
      longitudinal cohort study involved extensive baseline assessments, followed by a
      one-year follow-up on fall incidents. Falls occurred in 46% of the participants
      and the fall rate was 1.00 falls per person per year. The most important risk
      factors for falling in elderly persons with mild to moderate ID were (mild)
      severity of ID, (high) physical activity, (good) visuo-motor capacity, (good)
      attentional focus and (high) hyperactivity-impulsiveness, which together
      explained 56% of the fall risk. This pattern of risk factors identified suggests
      a complex interplay of personal and environmental factors in the aetiology of
      falls in elderly persons with ID. We recommend further research on the
      development of multifactorial screening procedures and individually tailored
      interventions to prevent falling in persons with ID.

PMID- 24029800
TI  - Reduction in primary genu recurvatum gait after aponeurotic calf muscle
      lengthening during multilevel surgery.
AB  - Knee hyperextension (genu recurvatum, GR) is often seen in children with
      bilateral spastic cerebral palsy (CP). Primary GR appears essential without
      previous treatment. As equinus deformity is suspected to be one of the main
      factors evoking primary GR, the purpose of this study was to determine whether
      lengthening the calf muscles to decrease equinus would decrease coexisting GR in
      children with bilateral spastic CP. In a retrospective study, 19 CP patients with
      primary GR (mean age: 9.4 years, 13 male, 6 female, 26 involved limbs) in whom an
      aponeurotic calf muscle lengthening procedure was performed during single-event
      multilevel surgery were included and investigated using three-dimensional gait
      analysis before and at a mean follow-up of 14 months after the procedure
      according to a standardized protocol. After calf muscle lengthening, a
      significant improvement in ankle dorsiflexion (9.5 degrees ) and a significant
      reduction (10.5 degrees ) in knee hyperextension (p<0.001) were found during mid
      stance of the gait cycle. Six limbs (23%) showed no improvement concerning knee
      hyperextension and were designated as nonresponders. In these patients no
      significant improvement in ankle dorsiflexion was found after surgery either.
      Improvement in ankle dorsiflexion and reduction in knee hyperextension in stance
      phase correlated significantly (r=0.46; p=0.019). These findings indicate that
      equinus deformity is a Major underlying factor in Primary GR and that calf muscle
      lengthening can effectively reduce GR in patients with CP.

PMID- 24029801
TI  - Prevalence of disabled people involved in Spanish Civil Guard's police activity.
AB  - Improving interventions with victims and offenders with disabilities requires
      analysis of the degree of prevalence of crimes in which these people are
      involved. For this purpose, data regarding interventions made by the Spanish
      Civil Guard between 2008 and 2010, in which 2099 people had some kind of
      disability, have been collected and analyzed, with particular regard to criminal
      offenses (felonies and/or misdemeanors). In this study, the relationship between
      the types of disability a person has and other variables like their connection to
      the incident, their gender, age, the relationship between victim and perpetrator,
      and the time and place of the events were all taken into consideration. The
      results show that most of the victims with disabilities served by the Spanish
      Civil Guard were male. The interventions were mainly aid and rescues. Criminal
      offenses were only 20% of the events. 

PMID- 24029802
TI  - Students' and teachers' perceptions of aggressive behaviour in adolescents with
      intellectual disability and typically developing adolescents.
AB  - This study investigated aggressive behaviour in Serbian adolescents with
      intellectual disability (ID) compared to typically developing peers. The sample
      consisted of both male and female adolescents aged 12-18 years. One hundred of
      the adolescents had ID, and 348 adolescents did not have ID. The adolescents were
      asked to complete the Reactive-Proactive Aggression Questionnaire (RPQ), and
      their teachers provided ratings of aggression for the adolescents using the
      Children's Scale of Hostility and Aggression: Reactive-Proactive (C-SHARP).
      Results indicated that adolescents reported a higher prevalence of aggressive
      behaviour than their teachers. Reactive aggression was more prevalent than
      proactive aggression in both subsamples. In the subsample of adolescents with ID,
      there were no sex or age differences for aggression. However, in the normative
      subsample, boys and older adolescents scored significantly higher on aggression.
      According to adolescent self-reports the prevalence of aggression was higher in
      adolescents without ID, while teachers perceived aggressive behaviour to be more
      prevalent in adolescents with ID. Scientific and practical implications are
      discussed. 

PMID- 24029803
TI  - Narrative spoken language skills in severely hearing impaired school-aged
      children with cochlear implants.
AB  - Cochlear implants have a significant positive effect on spoken language
      development in severely hearing impaired children. Previous work in this
      population has focused mostly on the emergence of early-developing language
      skills, such as vocabulary. The current study aims at comparing narratives, which
      are more complex and later-developing spoken language skills, of a contemporary
      group of profoundly deaf school-aged children using cochlear implants (n=66,
      median age=8 years 3 months) with matched normal hearing peers. Results show that
      children with cochlear implants demonstrate good results on quantity and
      coherence of the utterances, but problematic outcomes on quality, content and
      efficiency of retold stories. However, for a subgroup (n=20, median age=8 years 1
      month) of deaf children without additional disabilities who receive cochlear
      implantation before the age of 2 years, use two implants, and are raised with one
      spoken language, age-adequate spoken narrative skills at school-age are feasible.
      This is the first study to set the goals regarding spoken narrative skills for
      deaf children using cochlear implants. 

PMID- 24029804
TI  - A psychometric study of the Bayley Scales of Infant and Toddler Development - 3rd
      Edition for term and preterm Taiwanese infants.
AB  - The Bayley Scales of Infant and Toddler Development - 3rd Edition (Bayley-III)
      was updated to enhance its usefulness for contemporary child developmental
      assessment. However, recent data in Western countries have implicated the
      overestimation of child development by the new instrument. This study aimed to
      investigate the psychometric features of the Bayley-III for term and preterm
      infants in Taiwan. Forty-seven term infants and 167 preterm infants were
      prospectively examined with the Bayley Scales of Infant Development - 2nd Edition
      (BSID-II) and the Bayley-III at 6, 12, 18, and 24 months of age (corrected for
      prematurity). The psychometric properties examined included reliability,
      construct validity, and known-group validity. The intra- and inter-rater
      reliabilities of the Bayley-III were good to excellent. The correlations between
      the BSID-II and Bayley-III raw scores were good to excellent for the cognitive
      and motor items and low to excellent for the language items. Term infants
      achieved higher composite scores than preterm infants on all of the Bayley-III
      scales (p<0.05). However, their rates of developmental delay were lower than the
      previously established prevalence estimates. The Bayley-III cut-off composite
      score was adjusted 10-20, 1-13, and 12-24 points higher than 70 for optimal
      prediction of cognitive, language, and motor delay, respectively, as defined by
      the BSID-II index score<70. The Bayley-III is a reliable instrument that extends
      its previous edition, especially in early language assessment. However, the
      upward adjustment of its cut-off score is recommended for the accurate
      identification of developmental delay in term and preterm Taiwanese infants.

PMID- 24029805
TI  - Work engagement and job burnout within the disability support worker population.
AB  - The aim of this study was to explore work engagement and job burnout within the
      disability support worker (DSW) population, using the job demands-resources (JD
      R) model as a guiding theory. The research measured a set of work-related demands
      and resources related to working within the disability sector in order to assess
      which demands/resources account for a significant portion of unique variance when
      used to model DSW engagement and burnout. This study sampled 258 DSWs from across
      Australia who completed an online or paper questionnaire that included measures
      of engagement, burnout and the demands/resources of interest. With regard to
      demands, role ambiguity was significantly associated with the three engagement
      scores and the three burnout scores. It also accounted for the most unique
      variance in the three engagement scores (vigour [VI], dedication [DE] and
      absorption [AB]), and the personal accomplishment (PA) burnout score. With regard
      to resources, job feedback was significantly associated with two of the
      engagement scores (VI and DE) and all three burnout scores. It accounted for the
      most unique variance in VI and DE, and PA. In conclusion, this research adds to
      the existing disability workforce literature as it represents one of the first
      comprehensive investigations of work engagement within this population. Improved
      job descriptions, on-the-job feedback and the creation of specialist support
      workers are offered as recommendations to improve the psychosocial health of
      DSWs. 

PMID- 24029806
TI  - The relationship between awareness of intellectual disability, causal and
      intervention beliefs and social distance in Kuwait and the UK.
AB  - Evidence on lay beliefs and stigma associated with intellectual disability in an
      Arab context is almost non-existent. This study examined awareness of
      intellectual disability, causal and intervention beliefs and social distance in
      Kuwait. These were compared to a UK sample to examine differences in lay
      conceptions across cultures. 537 university students in Kuwait and 571 students
      in the UK completed a web-based survey asking them to respond to a diagnostically
      unlabelled vignette of a man presenting with symptoms of mild intellectual
      disability. They rated their agreement with 22 causal items as possible causes
      for the difficulties depicted in the vignette, the perceived helpfulness of 22
      interventions, and four social distance items using a 7-point Likert scale. Only
      8% of Kuwait students, yet 33% of UK students identified possible intellectual
      disability in the vignette. Medium to large differences between the two samples
      were observed on seven of the causal items, and 10 of the intervention items.
      Against predictions, social distance did not differ. Causal beliefs mediated the
      relationship between recognition of intellectual disability and social distance,
      but their mediating role differed by sample. The findings are discussed in
      relation to cultural practices and values, and in relation to attribution theory.
      In view of the apparent positive effect of awareness of the symptoms of
      intellectual disability on social distance, both directly and through the
      mediating effects of causal beliefs, promoting increased awareness of
      intellectual disability and inclusive practices should be a priority,
      particularly in countries such as Kuwait where it appears to be low. 

PMID- 24029807
TI  - The effect of different stimulus attributes on the attentional performance of
      children with attention deficit/hyperactivity disorder and dyslexia.
AB  - While teachers have traditionally used the interesting objects to increase
      student attention in the classroom, evidence supporting the effectiveness of this
      method is lacking. The present study investigated the influence of different
      stimulus attributes for typical developing students and for students with
      attention deficit/hyperactivity disorder (ADHD) and dyslexia. Thirty children
      with ADHD, 30 children with dyslexia, and 30 typical developing students were
      tested using a measuring tool that was constructed by the authors to assess their
      sustained attention and selective attention on the geometric-figure assessment
      and the interesting-figure assessment. The geometric-figure assessment included a
      square, circle, trapezium, and triangle; and the interesting-figure assessment
      included a house, cat, hand, and tree. While the typical developing group showed
      better selective attention on the geometric-figure assessment, there was no
      difference between the dyslexic group and the ADHD group with respect to
      selective attention. Furthermore, the typical developing and dyslexic groups did
      not differ in the geometric-figure assessment in sustained attention and were
      both better in this area than the ADHD group. In the interesting-figure
      assessment, the typical developing and dyslexic groups performed similarly in
      sustained attention, but selective attention of the dyslexic group improved more
      than the ADHD group, similar to the typical developing group. Both selective
      attention of the dyslexic group and sustained attention of the ADHD group showed
      positive significant differences in the interesting-figure assessment, but
      sustained attention of the dyslexic group and selective attention of the ADHD
      group showed little difference in the interesting-figure assessment.
      Surprisingly, the typical developing group did not show any significant
      difference in the interesting-figure assessment, possibly because they had
      previously demonstrated a ceiling effect in the geometric-figure assessment. 

PMID- 24029808
TI  - Body mass index, dietary intake and feeding problems of Turkish children with
      autism spectrum disorder (ASD).
AB  - The body mass index of 164 children (aged 4-18 years) attending four autism
      rehabilitation centers in Istanbul, Turkey, was determined and assessed using the
      BMI-for-age percentile charts by the World Health Organization (WHO). The mean
      intake of energy and nutrients of 115 children were calculated using three-day
      food records. The feeding assessment surveys filled in by the parents/caregivers
      indicated that the major feeding problem among children was food selectivity. The
      majority of the children were overweight or obese (58.5%). A total of 11% of
      children were found to be severely thin and thin. The calcium, zinc, vitamin B6
      and folate intake of the majority of children were inadequate. The salt
      consumption in all age groups and cholesterol intake in normal, overweight and
      obese children were high. 

PMID- 24029809
TI  - Sleep problems and language development in toddlers with Williams syndrome.
AB  - Sleep and related maternal beliefs were assessed in a narrow age range of 18
      children with Williams syndrome (WS) and 18 typically developing (TD) children.
      WS is a rare genetic disorder characterised by a complex physical, cognitive and
      behavioural phenotype. High prevalence of sleep difficulties in older children
      and adults with WS have been reported. Parents completed 6 questionnaires: the
      Brief Infant Sleep Questionnaire, Infant Sleep Vignettes Interpretation Scale,
      Pittsburgh Sleep Quality Index of Parents, Child Behaviour Checklist, MacArthur
      Communicative Development Inventory for Infants - Words and Gestures, and the
      Major (ICD-10) Depression Inventory. Compared to TD children, those with WS had
      shorter night sleep, more night wakings and wakefulness according to parental
      report. Regression analyses revealed that a proportion of the variance in
      language development scores in WS children could be explained by night sleep
      duration. Compared to control parents, the mothers of the WS group were more
      likely to describe their child's sleep as problematic and had higher rates of
      involvement with child sleep, yet they had a lesser tendency to interpret sleep
      problems as signs of distress and a greater tendency to emphasise limit setting.
      Approximately half of both groups of mothers experienced poor sleep quality. This
      was also related to maternal mood, and night wakefulness in the children with WS.
      This is the first study to quantify sleep difficulties in young children with WS
      in a narrow age range using maternal report. The possible negative effects on
      maternal sleep and mood, and the link between night sleep and language
      development in young children with WS, requires further detailed investigation. 

PMID- 24029810
TI  - Feasibility of multimodal 3D neuroimaging to guide implantation of intracranial
      EEG electrodes.
AB  - BACKGROUND: Since intracranial electrode implantation has limited spatial
      sampling and carries significant risk, placement has to be effective and
      efficient. Structural and functional imaging of several different modalities
      contributes to localising the seizure onset zone (SoZ) and eloquent cortex. There
      is a need to summarise and present this information throughout the pre/intra/post
      surgical course. METHODS: We developed and implemented a multimodal 3D
      neuroimaging (M3N) pipeline to guide implantation of intracranial EEG (icEEG)
      electrodes. We report the implementation of the pipeline for operative planning
      and a description of its use in clinical decision-making. RESULTS: The results of
      intraoperative application of the M3N pipeline demonstrated clinical benefits in
      all 15 implantation surgeries assessed. The M3N software was used to simulate
      placement of intracranial electrodes in 2 cases. The key benefits of using the
      M3N pipeline are illustrated in 3 representative case reports. CONCLUSION: We
      have demonstrated feasibility of the developed intraoperative M3N pipeline which
      serves as a prototype for clinical implementation. Further validity studies with
      larger sample groups are required to determine the utility of M3N in routine
      surgical practice.

PMID- 24029811
TI  - Horizontal transfer of DNA from the mitochondrial to the plastid genome and its
      subsequent evolution in milkweeds (apocynaceae).
AB  - Horizontal gene transfer (HGT) of DNA from the plastid to the nuclear and
      mitochondrial genomes of higher plants is a common phenomenon; however, plastid
      genomes (plastomes) are highly conserved and have generally been regarded as
      impervious to HGT. We sequenced the 158 kb plastome and the 690 kb mitochondrial
      genome of common milkweed (Asclepias syriaca [Apocynaceae]) and found evidence of
      intracellular HGT for a 2.4-kb segment of mitochondrial DNA to the rps2-rpoC2
      intergenic spacer of the plastome. The transferred region contains an rpl2
      pseudogene and is flanked by plastid sequence in the mitochondrial genome,
      including an rpoC2 pseudogene, which likely provided the mechanism for HGT back
      to the plastome through double-strand break repair involving homologous
      recombination. The plastome insertion is restricted to tribe Asclepiadeae of
      subfamily Asclepiadoideae, whereas the mitochondrial rpoC2 pseudogene is present
      throughout the subfamily, which confirms that the plastid to mitochondrial HGT
      event preceded the HGT to the plastome. Although the plastome insertion has been
      maintained in all lineages of Asclepiadoideae, it shows minimal evidence of
      transcription in A. syriaca and is likely nonfunctional. Furthermore, we found
      recent gene conversion of the mitochondrial rpoC2 pseudogene in Asclepias by the
      plastid gene, which reflects continued interaction of these genomes. 

PMID- 24029812
TI  - Feeling supported and abandoned: mixed messages from attendance at a rural
      community cardiac rehabilitation program in Australia.
AB  - PURPOSE: In 2010, the Healthy Heart (HH) community-based cardiac rehabilitation
      program was offered at Latrobe Community Health Service in rural Victoria,
      Australia. The 8-week program, based on National Heart Foundation guidelines,
      consisted of exercise sessions; health education on diet, stress, and smoking
      cessation; and behavioral change strategies. Participants were also informed
      about local community exercise opportunities. A program evaluation was conducted
      in 2011 to assess whether the content of the program was meeting the needs of
      participants and to identify what suggestions they had for improvement. METHODS:
      Eighteen patients had completed the HH program in 2010. Eight of these
      participants, 7 men and 1 woman, volunteered to take part in a focus group.
      Conventional content analysis was used to identify and group the common themes
      that emerged from the focus group discussions. RESULTS: Three themes were
      identified that reflected the participant experiences of attending the HH
      program. The first, "recovering confidence," described participant responses to
      the content of the sessions. The second, "putting it into practice," referred to
      their comments about taking responsibility for making lifestyle changes. The
      third, "feeling abandoned," emerged from the reported difficulty participants
      expressed about maintaining motivation for change after program completion.
      CONCLUSION: Participants rated the HH program as very successful by objective
      measures. However, they reported struggling to maintain self-management
      strategies postprogram. There is clearly a need to develop strategies that
      support cardiac rehabilitation participants over the longer-term.

PMID- 24029813
TI  - Adherence to a maintenance exercise program 1 year after pulmonary
      rehabilitation: what are the predictors of dropout?
AB  - PURPOSE: To evaluate adherence to a maintenance exercise program in patients with
      chronic obstructive pulmonary disease (COPD) and explore predictors for
      adherence. METHODS: Seventy patients with COPD were referred to a home-care
      maintenance exercise program after completing pulmonary rehabilitation (PR) in
      the rehabilitation center. Adherence (yes/no) to the maintenance program was
      assessed by a self-reported questionnaire, where adherence was defined as
      attending the maintenance program 1 year after PR. Early dropouts received a self
      reported questionnaire after 6 months and the remaining patients after 12 months.
      Lung function, exercise capacity, exercise self-efficacy, illness perceptions,
      health-related quality of life, levels of anxiety and depression, duration of PR,
      and the number of exacerbations were studied as possible predictors of adherence.
      RESULTS: Ten patients died or were lost to followup. Of the remaining 60
      patients, 73.3% and 63.3% were adherent to the maintenance exercise program after
      6 and 12 months, respectively. Forced expiratory volume in 1 second (FEV1) (P =
      .021), Hospital Anxiety and Depression Scale depression score (P = .025), and
      duration of PR (P = .018) were significant predictors of adherence to the
      maintenance program. CONCLUSION: Adherence to the maintenance exercise program
      included a 36.7% drop-out rate during the first year after completing PR.
      Experiencing exacerbations was the most reported reason for dropout. Poorer lung
      function, shorter initial PR course measured by reviewing patient records, and
      higher level of depressive symptoms were predictive of drop-out to the
      maintenance program. Adherence to the maintenance program needs to be improved
      for patients with lower FEV1, with signs of depression, or with a shorter initial
      PR course.

PMID- 24029814
TI  - Human health risks associated with dietary exposure to persistent organic
      pollutants (POPs) in river water in Korea.
AB  - Because of their persistence, bioaccumulation tendency, and toxicity,
      organochlorine pesticides (OCPs) were banned several decades ago. However, they
      are still detected in natural water and pose a serious risk to human health and
      the environment. In the present study, seven OCPs were measured in river water
      collected from 28 sampling sites between 2010 and 2011 in the Yeongsan (YS) and
      Seomjin (SJ) Rivers, Korea. Gas chromatography/high-resolution mass spectrometry
      (HRMS) was used for the chemical analysis. The potential health risks of
      consuming OCPs in fish were assessed in the monitoring region (YS and SJ River
      basins) by measuring the residual level of OCPs. The human health risks were
      characterized by considering both the exposure level and the corresponding cancer
      slope factors; we incorporated both deterministic and probabilistic approaches.
      The risks were calculated using the probabilistic Maximum Likelihood Estimation
      (MLE) method. Risk uncertainty and sensitivity were calculated by performing a
      Monte Carlo analysis. Of the six OCPs, dieldrin, heptachlor epoxide, and
      hexachlorobenzene exceeded the acceptable risk level in the heavy and light fish
      consumer groups. The cancer risks associated with these OCPs were 2.99*10(-6),
      5.81*10(-6) and 3.72*10(-6), respectively, using the deterministic approach and
      1.64*10(-5), 3.36*10(-2) and 5.52*10(-5), respectively, at the 95th percentile
      using the probabilistic approach. Because there is a high cancer risk associated
      with these three OCPs, individuals who consume large amounts of freshwater fish
      may be subject to a high risk of cancer. However, the calculations may have over-
      or underestimated the risk because of the uncertainty of the environmental
      concentration and fish intake rate or the use of left-censored monitoring data.

PMID- 24029815
TI  - Transcatheter renal ablation with absolute alcohol for resistant hypertension.

PMID- 24029817
TI  - Expression analysis and enzymatic characterization of phospholipase Cdelta4 from
      olive flounder (Paralichthys olivaceus).
AB  - Phospholipase Cdelta4 (PLCdelta4) plays a significant role in cell proliferation,
      tumorigenesis, and in an early stage of fertilization. Despite the
      characterization of the mammalian PLCdelta4, extensive study in aquatic organisms
      has not been carried out so far. Here, we performed the molecular and biochemical
      characterization of flatfish Paralichthys olivaceus PLCdelta4 (PoPLCdelta4) to
      understand its enzymatic properties and physiological functions. The olive
      flounder PLCdelta4 cDNA has an open reading frame (ORF) of 2,268 bp, and encodes
      a 755 amino acid polypeptide with a predicted molecular weight of 86 kDa. All the
      characteristic domains found in mammalian PLCdelta isoforms (PH domain, EF hands,
      an X-Y catalytic region, and a C2 domain) were found to be present in
      PoPLCdelta4. The mRNA expression analysis of PoPLCdelta4 showed that PoPLCdelta4
      is predominantly expressed in the brain, eye and heart tissues. Like other
      mammalian PLCdelta proteins, the enzyme activity of recombinant PoPLCdelta4 to
      phosphatidylinositol-4,5-bis-phosphate (PIP2) was noted to be concentration- and
      Ca(2+)-dependent. The structural features and biochemical characteristics of
      PoPLCdelta4 were found to be similar to those of mammalian PLCdelta4. This is the
      first demonstration of the expression analysis and enzymatic characterization of
      piscine PLCdelta4.

PMID- 24029818
TI  - Temporal changes in K-ras mutant fraction in lung tissue of big blue B6C3F1 mice
      exposed to ethylene oxide.
AB  - Ethylene oxide (EO) is a genotoxicant and a mouse lung carcinogen, but whether EO
      is carcinogenic through a mutagenic mode of action remains unclear. To
      investigate this question, 8-week-old male Big Blue B6C3F1 mice (10 mice/group)
      were exposed to EO by inhalation-6 h/day, 5 days/week for 4 weeks (0, 10, 50,
      100, or 200 ppm EO) and 8 or 12 weeks (0, 100, or 200 ppm EO). Lung DNA samples
      were analyzed for levels of 3 K-ras codon 12 mutations (GGT->GAT, GGT->GTT, and
      GGT->TGT) using ACB-PCR. No measureable level of K-ras codon 12 TGT mutation was
      detected (ie, all lung mutant fractions [MFs] <= 10-5). Four weeks of inhalation
      of 100 ppm EO caused a significant increase in K-ras codon 12 GGT->GTT MF
      relative to controls, whereas 50, 100, and 200 ppm EO caused significant
      increases in K-ras codon 12 GGT->GAT MF. In addition, significant inverse
      correlations were observed between K-ras codon 12 GGT->GTT MF and cII mutant
      frequency in the lungs of the same mice exposed to 50, 100, or 200 ppm EO for 4
      weeks. Surprisingly, 8 weeks of exposure to 100 and 200 ppm EO caused significant
      decreases in K-ras MFs relative to controls. Thus, the changes in K-ras MF as a
      function of cumulative EO dose were nonmonotonic and were consistent with EO
      causing early amplification of preexisting K-ras mutations, rather than induction
      of K-ras mutation through genotoxicity at codon 12. The possibility that these
      changes reflect K-ras mutant cell selection under varying degrees of oxidative
      stress is discussed.

PMID- 24029819
TI  - Disorder strongly enhances Auger recombination in conductive quantum-dot solids.
AB  - Auger recombination (AR) can be an important loss mechanism for optoelectronic
      devices, but it is typically not very efficient at low excitation densities. Here
      we show that in conductive quantum-dot solids, AR is the dominant charge carrier
      decay path even at excitation densities as low as 10-3 per quantum dot, and that
      AR becomes faster as the charge carrier mobility increases. Monte Carlo
      simulations reveal that this efficient AR results from charge carrier
      congregation in 'Auger hot spots': lower-energy sites that are present because of
      energy disorder. Disorder-enhanced AR is a general effect that is expected to be
      active in all disordered materials. The observed efficient AR is an issue of
      concern for devices that work at charge carrier densities in excess of ~10-3
      charge carriers per quantum dot. At the same time, efficient carrier congregation
      could be exploited for fast optical switching or to achieve optical gain in the
      near infrared.

PMID- 24029820
TI  - Constructing "proper" ROCs from ordinal response data using weighted power
      functions.
AB  - BACKGROUND: Receiver operating characteristic (ROC) analysis is the standard
      method for describing the accuracy of diagnostic systems where the decision task
      involves distinguishing between 2 mutually exclusive possibilities. The popular
      binormal curve-fitting model usually produces ROCs that are improper in that they
      do not have the ever-decreasing slope required by signal detection theory. Not
      infrequently, binormal ROCs have visible hooks that falsely imply worse-than
      chance diagnostic differentiation where the curve lies below the no-information
      diagonal. In this article, we present and evaluate a 2-parameter, weighted power
      function (WPF) model that always results in a proper ROC curve with a positive,
      monotonically decreasing slope. METHODS: We used a computer simulation study to
      compare results from binormal and WPF models. RESULTS: The WPF model produces ROC
      curves that are less biased and closer to the true values than are curves
      obtained using the binormal model. The better performance of the WPF model
      follows from its design constraint as a necessarily proper ROC. CONCLUSIONS: The
      WPF model fits a broader variety of data sets than previously published power
      function models while maintaining straightforward relationships among the
      original decision variable, specific operating points, ROC curve contours, and
      model parameters. Compared with other proper ROC models, the WPF model is
      distinctive in its simplicity, and it avoids the flaws of the conventional
      binormal ROC model.

PMID- 24029821
TI  - Remote distractor effects and saccadic inhibition: spatial and temporal
      modulation.
AB  - The onset of a visual distractor remote from a saccade target is known to
      increase saccade latency (the remote distractor effect [RDE]). In addition,
      distractors may also selectively inhibit saccades that would be initiated about
      90 ms after distractor onset (termed saccadic inhibition [SI]). Recently, it has
      been proposed that the transitory inhibition of saccades (SI) may underlie the
      increase in mean latency (RDE). In a first experiment, the distractor
      eccentricity was manipulated, and a robust RDE that was strongly modulated by
      distractor eccentricity was observed. However, the underlying latency
      distributions did not reveal clear evidence of SI. A second experiment
      manipulated distractor spatial location and the timing of the distractor onset in
      relation to the target. An RDE was again observed with remote distractors away
      from the target axis and under conditions with early-onset distractors that would
      be unlikely to produce SI, whereas later distractor onsets produced an RDE along
      with some evidence of an SI effect. A third experiment using a mixed block of
      target-distractor stimulus-onset asynchronies (SOAs) revealed an RDE that varied
      with both distractor eccentricity and SOA and changes to latency distributions
      consistent with the timing of SI. We argue that the notion that SI underpins the
      RDE is similar to the earlier argument that express saccades underlie the
      fixation offset (gap) effect and that changes in mean latency and to the shape of
      the underlying latency distributions following a visual onset may involve more
      than one inhibitory process. 

PMID- 24029822
TI  - Does linear separability really matter? Complex visual search is explained by
      simple search.
AB  - Visual search in real life involves complex displays with a target among multiple
      types of distracters, but in the laboratory, it is often tested using simple
      displays with identical distracters. Can complex search be understood in terms of
      simple searches? This link may not be straightforward if complex search has
      emergent properties. One such property is linear separability, whereby search is
      hard when a target cannot be separated from its distracters using a single linear
      boundary. However, evidence in favor of linear separability is based on testing
      stimulus configurations in an external parametric space that need not be related
      to their true perceptual representation. We therefore set out to assess whether
      linear separability influences complex search at all. Our null hypothesis was
      that complex search performance depends only on classical factors such as target
      distracter similarity and distracter homogeneity, which we measured using simple
      searches. Across three experiments involving a variety of artificial and natural
      objects, differences between linearly separable and nonseparable searches were
      explained using target-distracter similarity and distracter heterogeneity.
      Further, simple searches accurately predicted complex search regardless of linear
      separability (r = 0.91). Our results show that complex search is explained by
      simple search, refuting the widely held belief that linear separability
      influences visual search. 

PMID- 24029823
TI  - Defects activated photoluminescence in two-dimensional semiconductors: interplay
      between bound, charged, and free excitons.
AB  - Point defects in semiconductors can trap free charge carriers and localize
      excitons. The interaction between these defects and charge carriers becomes
      stronger at reduced dimensionalities, and is expected to greatly influence
      physical properties of the hosting material. We investigated effects of anion
      vacancies in monolayer transition metal dichalcogenides as two-dimensional (2D)
      semiconductors where the vacancies density is controlled by alpha-particle
      irradiation or thermal-annealing. We found a new, sub-bandgap emission peak as
      well as increase in overall photoluminescence intensity as a result of the
      vacancy generation. Interestingly, these effects are absent when measured in
      vacuum. We conclude that in opposite to conventional wisdom, optical quality at
      room temperature cannot be used as criteria to assess crystal quality of the 2D
      semiconductors. Our results not only shed light on defect and exciton physics of
      2D semiconductors, but also offer a new route toward tailoring optical properties
      of 2D semiconductors by defect engineering. 

PMID- 24029824
TI  - Stimuli-responsive hydrogel patterns for smart microfluidics and microarrays.
AB  - In this review, we highlight the properties, functions and applications of
      stimuli-responsive hydrogel patterns in bioanalytical applications. Stimuli
      responsive hydrogel patterns can be realized by well-established micro- and
      nanofabrication technologies such as photolithography and micromolding, and are
      currently adopted as active components for manipulation of flow and biosamples in
      microchannel and microarray systems. We overview the properties of stimuli
      responsive hydrogel materials and their fabrication methods along with some
      representative examples in microfluidics and microarrays. 

PMID- 24029825
TI  - The capsular warning syndrome reconsidered.

PMID- 24029826
TI  - Dermal histomorphology in post-bariatric patients: bilopancreatic diversion
      versus gastric bypass: reply.

PMID- 24029827
TI  - Oxo-carboxylato-molybdenum(VI) complexes possessing dithiolene ligands related to
      the active site of type II DMSOR family molybdoenzymes.
AB  - Spectroscopic and kinetic studies indicate that oxo-carboxylato-molybdenum(VI)
      bis-dithiolene complexes, (Mo(VI)O(p-X-OBz)L2), have been generated at low
      temperature as active site structural models for the type II class of
      pyranopterin molybdenum DMSOR family enzymes. A DFT analysis of low energy charge
      transfer bands shows that these complexes possess a Mo-S(dithiolene) pi-bonding
      interaction between the Mo(d(xy)) redox active molecular orbital and a cis
      S(p(z)) donor orbital located on one of the dithiolene ligands.

PMID- 24029832
TI  - Novel compound heterozygous mutations resulting in cone dystrophy with
      supernormal rod response.

PMID- 24029833
TI  - Inter and intra-rater reliability of mobile device goniometer in measuring lumbar
      flexion range of motion.
AB  - BACKGROUND: Evaluation of range of motion (ROM) is integral part of assessment of
      musculoskeletal system. This is required in health fitness and pathological
      conditions; also it is used as an objective outcome measure. Several methods are
      described to check spinal flexion range of motion. Different methods for
      measuring spine ranges have their advantages and disadvantages. Hence, a new
      device was introduced in this study using the method of dual inclinometer to
      measure lumbar spine flexion range of motion (ROM). OBJECTIVES: To determine
      Intra and Inter-rater reliability of mobile device goniometer in measuring lumbar
      flexion range of motion. METHOD: iPod mobile device with goniometer software was
      used. The part being measure i.e the back of the subject was suitably exposed.
      Subject was standing with feet shoulder width apart. Spinous process of second
      sacral vertebra S2 and T12 were located, these were used as the reference points
      and readings were taken. Three readings were taken for each: inter-rater
      reliability as well as the intra-rater reliability. Sufficient rest was given
      between each flexion movement. RESULTS: Intra-rater reliability using ICC was
      r=0.920 and inter-rater r=0.812 at CI 95%. Validity r=0.95. CONCLUSION: Mobile
      device goniometer has high intra-rater reliability. The inter-rater reliability
      was moderate. This device can be used to assess range of motion of spine flexion,
      representing uni-planar movement.

PMID- 24029834
TI  - Highly sensitive protein detection based on a novel probe with catalytic activity
      combined with a signal amplification strategy: assay of MDM2 for cancer staging.
AB  - A novel probe with catalytic activity is used for highly sensitive MDM2
      detection. 

PMID- 24029835
TI  - Social amoeba farmers carry defensive symbionts to protect and privatize their
      crops.
AB  - Agricultural crops are investments that can be exploited by others. Farmer clones
      of the social amoeba Dictyostelium discoideum carry bacteria to seed out new food
      populations but they also carry other non-food bacteria such as Burkholderia spp.
      Here we demonstrate that these farmer-carried Burkholderia inhibit the growth of
      non-farmer D. discoideum clones that could exploit the farmers' crops. Using
      supernatants, we show that inhibition is due to molecules secreted by
      Burkholderia. When farmer and non-farmer amoebae are mixed together at various
      frequencies and allowed to complete the social stage, the ability of non-farmers
      to produce spores falls off rapidly with an increase in the percentage of farmers
      and their defensive symbionts. Conversely, farmer spore production is unaffected
      by the frequency of non-farmers. Our results suggest that successful farming is a
      complex evolutionary adaptation because it requires additional strategies, such
      as recruiting third parties, to effectively defend and privatize crops. 

PMID- 24029836
TI  - Global mental health: a sustainable post Millennium Development Goal?

PMID- 24029837
TI  - Maternal depression in low- and middle-income countries.
AB  - Maternal depression is an enormous, neglected public health problem in low- and
      middle-income countries (LAMICs). Evidence is accumulating to guide intervention,
      focused on integrating mental health care into routine maternal and child health
      care through a task sharing approach. Key questions around the 'who, what, when,
      where and how?' of intervention will be discussed in relation to the existing
      evidence base. A great deal of attention is now being paid to maternal health in
      LAMICs. By seizing this opportunity to also attend to maternal mental health
      care, important public health gains can be made for both the mother and her
      children. 

PMID- 24029838
TI  - Stigma and discrimination as a barrier to mental health service utilization in
      India.
AB  - Stigma towards, and discrimination against, people with mental disorders is an
      important barrier to mental health service utilization in India. It contributes
      to delays in seeking care, impedes timely diagnosis and treatment for mental
      disorders, serves as an impediment to recovery and rehabilitation, and ultimately
      reduces the opportunity for fuller participation in life. In India there is a
      need to generate evidence base for context specific interventions that will
      address negative attitudes towards people with mental disorders and ensure
      implementation of these interventions by involving users, care-givers, community
      health workers and mental health service providers. 

PMID- 24029839
TI  - Mental health in humanitarian settings: shifting focus to care systems.
AB  - Mental health in low- and middle income countries has received increasing
      attention. This attention has shifted focus, roughly moving from demonstrating
      the burden of mental health problems, to establishing an evidence base for
      interventions, to thinking about care delivery frameworks. This paper reviews
      these trends specifically for humanitarian settings and discusses lessons
      learned. Notably, that mental health assessments need to go beyond measuring the
      impact of traumatic events on circumscribed psychiatric disorders; that evidence
      for effectiveness of interventions is still too weak and its focus too limited;
      and that development of service delivery in the context of instable community and
      health systems should be an area of key priority. 

PMID- 24029840
TI  - Mental health services development in Latin America and the Caribbean:
      achievements, barriers and facilitating factors.
AB  - Mental health services reforms in Latin America and the Caribbean in the last 20
      years have led to a significant improvement of mental health services. They also
      contributed to the development of new evidence that may help the implementation
      of future reforms. These advances, however, were clearly insufficient to respond
      to the huge challenges countries of Latin American and the Caribbean face to
      improve mental health services. Insufficient funding, one of the most important
      barriers to mental health services development found in most countries, was
      related to the absence of a strong consensus among all stakeholders and the
      weakness of user and family associations. Other barriers were the lack of
      technical capacity of the coordination unit responsible for development of
      services in the ministries of health, resistance from professionals towards
      changing to new models of care and lack of human resources. Transition to
      democracy in some countries and natural disasters proved to be windows of
      opportunity for mental health services reform. Facilitating factors included
      alliance with the human rights defence movement, development of research capacity
      in Latin American and the Caribbean countries, and international cooperation. 

PMID- 24029841
TI  - Forced migration and mental health: prolonged internal displacement, return
      migration and resilience.
AB  - Forced internal displacement has been rising steadily, mainly due to conflict.
      Many internally displaced people (IDP) experience prolonged displacement. Global
      research evidence suggests that many of these IDP are at high risk for developing
      mental disorders, adding weight to the global burden of disease. However,
      individual and community resilience may act as protective factors. Return
      migration may be an option for some IDP populations, especially when conflicts
      end, although return migration may itself be associated with worse mental health.
      Limited evidence is available on effects of resettlement or return migration
      following prolonged forced internal displacement on mental health. Also, the role
      of resilience factors remains to be clarified following situations of prolonged
      displacement. The public health impact of internal displacement is not clearly
      understood. Epidemiological and interventional research in IDP mental health
      needs to look beyond medicalised models and encompass broader social and cultural
      aspects. The resilience factor should be integrated and explored more in mental
      health research among IDP and a clearly focused multidisciplinary approach is
      advocated. 

PMID- 24029842
TI  - Collaborative care for depression: a literature review and a model for
      implementation in developing countries.
AB  - Depression will soon be the leading cause of disability in developing countries
      but effective treatments are not widely available. There is compelling evidence
      for the effectiveness and cost-effectiveness of the multicondition collaborative
      care (MCC) model for depression in developing and developed countries. In the MCC
      model integrated care for depression is provided along with care for different
      non-communicable disorders. MCC has been shown to reduce hyperglycaemia and
      hyperlipidaemia and can lead to depression-free days when integrated care for
      depression and diabetes is provided. However, due to limited resources, it is not
      possible to make this effective model of care available at the population level.
      It is suggested that a public health intervention based on the MCC model can lead
      to better care for depression in developing countries. A public health programme
      of MCC which provides treatment for depression, diabetes and hypertension in a
      collaborative care programme will be a cost-effective way of providing treatment
      for depression in developing countries. This will cater for the leading cause of
      disability (unipolar depression) and the leading projected causes of mortality
      (ischaemic heart disease and cerebrovascular disease) in low-income and middle
      income countries. 

PMID- 24029843
TI  - Intimate partner violence and perinatal common mental disorders among women in
      rural Vietnam.
AB  - INTRODUCTION: Intimate partner violence against women (IPV) is regarded
      increasingly as a public health problem worldwide. The overall aim of this study
      was to examine the associations between different exposures to IPV and women's
      mental health during pregnancy and after childbirth in rural Vietnam. METHODS:
      This was a secondary analysis of data generated in a community-based longitudinal
      investigation in which a cohort of pregnant women were recruited and followed
      until 6 months after childbirth. Different forms of IPV were measured by the
      Intimate Partner Violence section of the WHO Multi-Country Study on Women's
      Health and Domestic Violence Against Women questionnaire. The Edinburgh Postnatal
      Depression Scale-Vietnam Validation was used to assess symptoms of the common
      perinatal mental disorders of depression and anxiety (CPMD). RESULTS: Overall,
      497 women were recruited and complete data were available from 417 (83.9%).
      Exposure to either lifetime or perinatal IPV including emotional abuse, physical
      violence and sexual violence was associated with increased CPMD symptoms
      (adjusted odds ratio, OR, ranges 1.3-14.3) and suicidal thoughts (OR ranges 4.7
      6.1) in women during pregnancy and after childbirth. Experiencing more than one
      form of IPV increased the magnitude of the association between IPV and CPMD
      symptoms and thoughts of suicide. CONCLUSION: It is clearly essential in this and
      other resource-constrained settings to address emotional, physical and sexual
      violence perpetrated by an intimate partner in any strategies to reduce the risk
      of perinatal mental health problems in women.

PMID- 24029844
TI  - Understanding the local context for the application of global mental health: a
      rural South African experience.
AB  - BACKGROUND: The global mental health movement has supplied ample evidence of
      treatment gaps for mental health care in low and middle-income countries. It is
      also clear that substantial progress has been made in developing an evidence base
      for innovative treatments which have been shown to work. It is only through rich
      and detailed understandings of local contexts and individual experiences that the
      challenges global mental health faces can be fully appreciated. METHODS: In this
      article, we use a single, qualitative case study from one context and of one
      family affected by mental disorder. This is to elucidate core issues which we
      regard as key to further developments in the global mental health agenda.
      RESULTS: Core issues are poor mental health literacy, transport and lack of
      outreach, limitations of formal health care, challenges at the interface with
      indigenous health care and lack of follow-up and rehabilitation. CONCLUSION: We
      propose shifting the focus of mental health care from cure to promotion and
      prevention, using an interdisciplinary team of lay and trained health workers
      from the professional, folk and popular sectors. The challenges are complex, as
      this small study shows, but it is only by looking closely at local conditions
      that it is possible to develop interventions which are contextually appropriate
      and make optimal use of local resources.

PMID- 24029845
TI  - Outcomes of the mental health and development model in rural Kenya: a 2-year
      prospective cohort intervention study.
AB  - BACKGROUND: The aim of this study was to evaluate outcomes for participants in
      BasicNeeds' Mental Health and Development programme in rural Kenya. METHODS: All
      new entrants to the programme in the Meru South and Nyeri North districts were
      enrolled in the study over a 3-month period (n = 203). Assessments of mental
      health, functioning, economic status and quality of life were conducted at
      baseline and at 1-year and 2-year follow up, using a single group cohort design.
      RESULTS: Over the 2 years there were significant improvements in scores on the
      General Health Questionnaire (21.5 [95% CI: 20.2-22.8] to 6 [95% CI: 4.8-7.2] p <
      0.01), Global Assessment of Functioning scale (78 [95% CI: 75.5-80.3] to 94 [95%
      CI: 90.7-97.3] p < 0.01), summed WHO Quality of Life-Brief scale (39.5 [95% CI:
      38.6-40.4] to 57.2 [95% CI: 56.2-58.3] p < 0.01) and the proportion who were
      engaged in either income generation or productive work (45.3-64.0%, p < 0.01).
      CONCLUSIONS: The mental health and development model shows improvements in mental
      health, functioning, income generation and quality of life among people living
      with severe mental illness in rural Kenya. The findings demonstrate the
      feasibility and benefits of integrating mental health and poverty alleviation
      components in mental health care in Africa.

PMID- 24029846
TI  - Care-seeking behaviour among individuals with TB symptoms in Jogjakarta Province,
      Indonesia: a community-based study.
AB  - BACKGROUND: Care-seeking behaviour of individuals with TB symptoms is a critical
      factor in early detection and treatment. Thorough understanding of determinants
      of the care-seeking process helps TB programme managers to improve TB case
      finding. The aim of this study was to assess determinants of care-seeking
      behaviour among patients with suspected TB at the population level. METHODS: A
      cross-sectional survey was conducted among adults with cough for >2 weeks. Data
      on sociodemographics, onset of TB symptoms, TB knowledge, health facility visited
      and duration of each visit were collected. RESULTS: Of the 746 respondents
      interviewed, approximately 10% had not yet sought care. Of those who sought care,
      less than one-half presented directly to medical healthcare providers. Being
      female and having multiple symptoms were associated with care-seeking action. The
      duration of patient delay (i.e. time between onset of symptoms and visiting a
      health provider) was relatively short, which may be due to the availability of an
      extended network of healthcare providers in Jogjakarta Province. Being male, a
      student or self-employed were associated with longer delay in presentation.
      CONCLUSIONS: Patient delay was relatively short. Efforts need to be focused on
      encouraging individuals with suspected TB to seek appropriate services through
      health education and quality improvement of health providers.

PMID- 24029847
TI  - Price discrimination in essential medicines: evidence from International Drug
      Price Indicator Guide data.
AB  - BACKGROUND: Few data are available on what donors, governments and other
      implementing organisations pay for the medicines they procure. To partly address
      this shortcoming, we analyse transactions of pharmaceuticals on the WHO's
      essential medicines list. Our objective was to identify the determinants of
      prices paid for these drugs. METHODS: We used data from the 2008 version of the
      International Drug Price Indicator Guide. We normalised transactions by
      representing their value as a 'price per daily dose'. We used a mixed-effects
      regression model to quantify the impact of observable characteristics on prices
      paid. RESULTS: We present evidence of first-degree price discrimination in the
      market for essential medicines. We find that as a country's per capita wealth
      doubles, prices paid for the same pharmaceutical increase by 33%. CONCLUSIONS:
      These data indicate that purchasing agents from wealthier countries pay more for
      essential medicines, all factors constant. This behaviour is not a form of
      development assistance for health but rather is indicative of inefficient markets
      in which buyers' lack of information enables suppliers to charge higher prices
      than they could otherwise.

PMID- 24029848
TI  - Correlates of lower comprehension of informed consent among participants enrolled
      in a cohort study in Pune, India.
AB  - BACKGROUND: Optimum comprehension of informed consent by research participants is
      essential yet challenging. This study explored correlates of lower comprehension
      of informed consent among 1334 participants of a cohort study aimed at estimating
      HIV incidence in Pune, India. METHODS: As part of the informed consent process, a
      structured comprehension tool was administered to study participants.
      Participants scoring >=90% were categorised into the 'optimal comprehension
      group', whilst those scoring 80-89% were categorised into the 'lower
      comprehension group'. Data were analysed to identify sociodemographic and
      behavioural correlates of lower consent comprehension. RESULTS: The mean +/- SD
      comprehension score was 94.4 +/- 5.00%. Information pertaining to study-related
      risks was not comprehended by 61.7% of participants. HIV-negative men (adjusted
      OR [AOR] = 4.36, 95% CI 1.71-11.05) or HIV-negative women (AOR = 13.54, 95% CI
      6.42-28.55), illiteracy (AOR= 1.65, 95% CI 1.19-2.30), those with a history of
      multiple partners (AOR = 1.73, 95% CI 1.12-2.66) and those never using condoms
      (AOR = 1.35, 95% CI 1.01-1.82) were more likely to have lower consent
      comprehension. CONCLUSIONS: We recommend exploration of domains of lower consent
      comprehension using a validated consent comprehension tool. Improved education in
      these specific domains would optimise consent comprehension among research
      participants.

PMID- 24029849
TI  - Addressing gender inequity in HIV care in rural Lesotho: the 'Male Initiative'.
AB  - BACKGROUND: Lesotho is a nation in Southern Africa with an HIV prevalence of 25%.
      Males are less likely to access HIV services and there is a need for strategies
      to improve male participation in HIV care. This paper describes the development
      and implementation of the Male Initiative to increase male participation in HIV
      services. METHODS: A combination of qualitative and quantitative methods were
      used to describe the components, process, organization, participation and
      potential impact of the Male Initiative. RESULTS: The Male Initiative was
      developed in partnership with local village chiefs, traditional healers and
      spiritual leaders. It used the traditional male meeting structure known as the
      Pitso-ea-banna to deliver messages about HIV care. 1311 men participated in five
      Male Initiative meetings over a 30 month period from June 2006-31 December, 2008.
      Male enrollment increased from 32% in 2006 to 36.8% in 2008, a trend which
      approached statistical significance (p = 0.07) and suggests potential
      programmatic impact that merits further study. CONCLUSION: Gender inequalities in
      enrollment in HIV care can be addressed through programs developed in partnership
      with local leaders and delivered in culturally accepted settings.

PMID- 24029850
TI  - Neglected tropical diseases: comparison of the costs of integrated and vertical
      preventive chemotherapy treatment in Niger.
AB  - BACKGROUND: This study presents evidence on the cost of integrated preventive
      chemotherapy treatment (PCT) to control trachoma, schistosomiasis, lymphatic
      filariasis and soil-transmitted helminthiasis (STH) in Niger. Integrated PCT
      costs are compared with the costs of vertical PCT control. METHODS: Data were
      analysed for the integrated PCT of 2008 and 2009 in six districts. Receipts,
      treatment registers, coverage forms and drug registers provided cost and
      treatment information. Economic costs of the time spent on campaign activities by
      government staff was derived from a survey of 56 staff. Integrated control costs
      were compared with vertical programmes undertaken in 2005 using 2009 constant
      prices. RESULTS: The average economic cost of integrated PCT was
      US$0.19/treatment excluding drugs (US$0.38 for a district with two drug
      treatments). The average financial cost was US$0.09/treatment (US$0.18 for a
      district with two drug treatments).The average financial cost of vertical
      treatment was US$0.167 for trachoma, US$0.10 for schistosomiasis and STH and
      US$0.075 for lymphatic filariasis. The integrated programme had savings of 16%
      and 21% in programme costs in 2008 and 2009, respectively, compared with the
      vertical programmes. CONCLUSION: Further work is needed to forecast the
      effectiveness of alternative long-term integrated treatment strategies for
      control and/or elimination of neglected tropical diseases.

PMID- 24029851
TI  - The distinct effects of lipid emulsions used for "lipid resuscitation" on gating
      and bupivacaine-induced inhibition of the cardiac sodium channel Nav1.5.
AB  - BACKGROUND: Systemic administration of lipid emulsions is an established
      treatment for local anesthetic intoxication. However, it is unclear by which
      mechanisms lipids achieve this function. The high cardiac toxicity of the
      lipophilic local anesthetic bupivacaine probably results from a long-lasting
      inhibition of the cardiac Na channel Nav1.5. In this study, we sought to
      determine whether lipid emulsions functionally interact with Nav1.5 or counteract
      inhibition by bupivacaine. METHODS: Human embryonic kidney cells expressing human
      Nav1.5 were investigated by whole-cell patch clamp. The effects of Intralipid(r)
      and Lipofundin(r) were explored on functional properties and on bupivacaine
      induced inhibition. RESULTS: Intralipid and Lipofundin did not affect the voltage
      dependency of activation, but induced a small hyperpolarizing shift of the steady
      state fast inactivation and impaired the recovery from fast inactivation.
      Lipofundin, but not Intralipid, induced a concentration-dependent but voltage
      independent tonic block (42% +/- 4% by 3% Lipofundin). The half-maximal
      inhibitory concentration (IC50) values for tonic block by bupivacaine (50 +/- 4
      uM) were significantly increased when lipids were coapplied (5% Intralipid: 196
      +/- 22 uM and 5% Lipofundin: 103 +/- 8 uM). Use-dependent block by bupivacaine at
      10 Hz was also reduced by both lipid emulsions. Moreover, the recovery of
      inactivated channels from bupivacaine-induced block was faster in the presence of
      lipids. CONCLUSIONS: Our data indicate that lipid emulsions reduce rather than
      increase availability of Nav1.5. However, both Intralipid and Lipofundin partly
      relieve Nav1.5 from block by bupivacaine. These effects are likely to involve not
      only a direct interaction of lipids with Nav1.5 but also the ability of lipid
      emulsions to absorb bupivacaine and thus reduce its effective concentration.

PMID- 24029852
TI  - Correspondence by Charles T. Jackson containing the earliest known illustrations
      of a Morton ether inhaler.
AB  - A letter, dated December 1, 1846, from Charles T. Jackson, MD, to Josiah D.
      Whitney contains a previously unreported description of a Morton ether inhaler
      and the only known contemporaneous hand-drawn illustrations of this type of ether
      inhaler. This letter and 2 other known letters on ether anesthesia were probably
      carried from Boston, MA, to Liverpool, United Kingdom, on the same paddle steamer
      (Acadia) that carried the well-known letter from Jacob Bigelow, MD, to Francis
      Boott, MD. 

PMID- 24029853
TI  - It's still plagiarism.

PMID- 24029854
TI  - A comparison between the Bonfils Intubation Fiberscope and McCoy laryngoscope for
      tracheal intubation in patients with a simulated difficult airway.
AB  - BACKGROUND: The Bonfils Intubation Fibrescope (Bonfils) and the McCoy
      laryngoscope (McCoy) are airway devices designed to assist tracheal intubation in
      difficult cases. Individually, both the Bonfils and McCoy have demonstrated
      superiority to the Macintosh laryngoscope in a simulated difficult airway. In
      this study, we compared the Bonfils with the McCoy laryngoscope in patients whose
      tracheal intubation had been intentionally hindered. Our primary hypothesis was
      that there is a significant difference in the rate of success for tracheal
      intubation when using the Bonfils or McCoy laryngoscope in patients with an
      intentionally hindered airway. METHODS: Patients undergoing elective surgery and
      requiring general anesthesia and endotracheal intubation were randomized to have
      intubation performed with either the Bonfils or McCoy laryngoscope. All patients
      were fitted with a hard cervical collar to simulate a difficult airway. Data
      collected included the success rate of endotracheal intubation, the time taken
      for intubation, the number of attempts required, the use of further aids to
      intubation, hemodynamic variables, and the incidence of adverse events. The
      primary end point was the relative rate of successful tracheal intubation.
      Categorical outcome measures were compared using the chi test, or Fisher exact
      test where appropriate, and the Mann-Whitney U test or unpaired Student t test
      where data were continuous. For the nonnormally distributed data, log
      transformation was adopted, and t test was performed if normalcy was achieved.
      RESULTS: Sixty adult patients were recruited and randomized into 2 groups of 30
      patients each. There was no difference in the rate of successful intubation
      between groups (95% confidence interval [CI], -11.6% to 11.6%), with a 100%
      success rate achieved in both groups. We found no statistically significant
      differences between groups in the time taken for intubation (P = 0.32, 95% CI,
      0.90-1.41) and percentage of single attempts (P = 0.47, 95% CI, -30.3% to 9.7%).
      However, further aids to intubation were required more frequently when using the
      McCoy laryngoscope (P < 0.001, 95% CI, 0.17-0.46), with 18 patients in the McCoy
      group requiring the use of an elastic bougie, and no patients in the Bonfils
      group requiring any aids. There were no significant differences found in the
      rates of adverse events. CONCLUSIONS: In the hands of trained operators, there
      appears to be no clinically significant difference in success, time to
      intubation, or adverse outcomes, when comparing the Bonfils with the McCoy
      laryngoscope, in the setting of a simulated difficult airway. The choice to use
      either device should remain based on appropriate patient selection, available
      aids, individual operator's experience, and economic circumstances.

PMID- 24029855
TI  - The use of cognitive aids during emergencies in anesthesia: a review of the
      literature.
AB  - Cognitive aids are prompts designed to help users complete a task or series of
      tasks. They may take the form of posters, flowcharts, checklists, or even
      mnemonics. It has been suggested that the use of cognitive aids improves
      performance and patient outcomes during anesthetic emergencies; however, a
      systematic assessment of the evidence is lacking. The aim of this literature
      review was to determine (1) whether cognitive aids improve performance of
      individuals and teams and (2) whether recommendations can be made for future
      cognitive aid design, testing, and implementation. Medical, nursing, and
      psychology databases were searched using broad criteria to find cognitive aids
      that have been reported in the literature for use in anesthetic emergencies. The
      reference lists of the articles selected for review were also screened to
      identify additional studies. Selected articles that described the evaluation of
      cognitive aids used in anesthetic emergencies were reviewed to determine how the
      content of the aid was derived, how the design was evaluated, and the success of
      the aid in improving technical and team performance. The search yielded 22
      cognitive aids developed to support clinicians during anesthetic emergencies that
      had been evaluated in 23 studies. Ten studies using simulation suggested that
      technical performance improves with the use of cognitive aids in some anesthetic
      emergencies such as malignant hyperthermia, cardiopulmonary resuscitation, and
      airway management. However, in 3 of the simulator-based evaluations, participants
      had either no improvement or took longer to diagnose and treat and made more
      incorrect diagnoses. Four studies investigated the effect of the aids on teamwork
      with differing conclusions. One study suggested improved participants'
      coordination patterns and one found aids improved their decision-making scores,
      but 2 other studies indicated that there was no improvement and even provided
      evidence of reduced levels of team communication when teams used a cognitive aid
      in simulated conditions. The designs of cognitive aids were rarely considered.
      Education may compensate for a poorly designed aid, but only by ingraining
      correct actions for situations in which the aid provides little or no guidance.
      Cognitive aids should continue to be developed from established clinical
      guidelines where guidelines exist. They would also benefit from more extensive
      simulation-based usability testing before use. Further evidence is required to
      explore the effects of cognitive aids in anesthetic emergencies, how they affect
      team function, and their design considerations. 

PMID- 24029856
TI  - Is dilutional coagulopathy induced by different colloids reversible by
      replacement of fibrinogen and factor XIII concentrates?
AB  - BACKGROUND: In this in vitro trial, we assessed the effect on blood coagulation
      of 60% dilution with different colloids and investigated reversibility by
      replacement of factor XIII (F XIII), fibrinogen, and the combination of
      fibrinogen and F XIII. METHODS: Using the blood of 12 volunteers, the following
      measurements were performed at baseline and after 60% dilution with (hydroxyethyl
      starch solutions) HES 130/0.42, gelatin, or balanced gelatin solution: blood gas
      analyses, coagulation factor concentrations (F I, F II, F VII, F VIII, F XIII),
      impedance aggregometry (Multiplate(r)), and rotational thromboelastometry
      (ROTEM). Then F XIII and fibrinogen as well as a combination of both were added,
      in concentrations corresponding to 6 g fibrinogen and 1250 IU F XIII in adults.
      ROTEM measurements and determination of factor concentrations were again
      performed. RESULTS: Colloid dilution led to a significant reduction of fibrinogen
      polymerization, especially with HES. Platelet function was impaired by all
      colloids, with gelatin having a significantly greater effect (area under the
      curve, collagen Test, P <= 0.008) than HES and balanced gelatin solution. The
      substitution of F XIII only did not improve clot formation. Substitution of
      fibrinogen improved the polymerization of fibrinogen in dilutions with gelatin
      and balanced gelatin solution (P = 0.002), whereas HES-induced coagulopathy could
      not be corrected. The combination of fibrinogen and F XIII showed a better effect
      than the addition of fibrinogen only for certain variables. CONCLUSION:
      Coagulation and platelet function are impaired by all 3 colloids. However, in
      vitro gelatin-induced coagulopathy was significantly more reversible than HES
      induced coagulopathy.

PMID- 24029857
TI  - Percutaneous closure of an incompetent aortic valve using an occluder device in a
      patient with left ventricular assist device.

PMID- 24029858
TI  - Cesarean delivery in the hybrid operating suite: a promising new location for
      high-risk obstetric procedures.
AB  - BACKGROUND: The increasing cesarean delivery rate and attendant placental
      implantation abnormalities, coupled with increasing general medical complexity in
      the obstetric population, has driven innovation to optimize the care of high-risk
      parturients during delivery. Novel and multidisciplinary approaches and locations
      may enhance the options available for care. METHODS: We reviewed the records of
      all 11 patients who underwent cesarean delivery in our hybrid operating suite
      between December 2007 and March 2013 and describe the high-risk cesarean
      deliveries. RESULTS: The most common indication for the use of the hybrid
      operating suite was an increased risk of hemorrhage, most commonly due to
      abnormal placental implantation. Other indications included cardiovascular
      disease and intracranial pathology. CONCLUSION: The hybrid operating suite may be
      an alternative location for obstetric delivery, and our experience suggests that
      this environment may prove advantageous for patients with a variety of comorbid
      conditions.

PMID- 24029859
TI  - Lower extremity performance following ACL rehabilitation in the KANON-trial:
      impact of reconstruction and predictive value at 2 and 5 years.
AB  - BACKGROUND: The additional effect of anterior cruciate ligament (ACL)
      reconstruction on muscle strength and physical performance after a structured
      exercise programme is not well understood. OBJECTIVES: To investigate and compare
      muscle strength and physical performance test results after a structured exercise
      programme, in young active adults with acute ACL injury, between those treated
      with and without ACL reconstruction (ACLR) and to evaluate these test results as
      predictors of clinical outcomes 2 and 5 years after injury. STUDY DESIGN:
      Prospective cohort study. METHODS: In a treatment randomised controlled trial of
      acute ACL injury (the KANON-study), 87/121 young active adults underwent two
      muscle strength tests and five physical performance tests after a structured
      exercise programme (median 37 (IQR 24) weeks after injury). Results were
      presented and compared as limb symmetry indices (LSI); endpoints in predictive
      analyses were having a delayed ACLR over the first 5 years and self-reported knee
      function (Knee injury and Osteoarthritis Outcome Score; KOOS4) at 2 and 5 years.
      RESULTS: Overall, 74-95% of patients had LSI>=90% in the individual tests, with
      no difference between treatment groups (p=0.08-0.92). Results of the one-leg rise
      tests predicted KOOS4 at 2 and 5 years (R2=0.25 and 0.24, p=0.001 and 0.002) and
      vertical hop results predicted having a delayed ACLR over a 5-year course after
      injury (p=0.048) in those starting with exercise alone (n=21). CONCLUSIONS: After
      an acute ACL tear, the majority of young active adults regain physical
      performance and muscle strength after a structured exercise programme, with or
      without surgical reconstruction. Poor physical performance at the end of
      rehabilitation predicted worse patient-reported outcomes at 2 and 5 years
      regardless of treatment. REGISTRATION NUMBER: ISRCTN84752559.

PMID- 24029862
TI  - Obesity and vascular disease: From bench to bedside.
AB  - N/A.

PMID- 24029861
TI  - A narrow-band ultraviolet B course improves vitamin D balance and alters
      cutaneous CYP27A1 and CYP27B1 mRNA expression levels in haemodialysis patients
      supplemented with oral vitamin D.
AB  - BACKGROUND/AIMS: Chronic kidney disease (CKD) patients on dialysis are prone to
      vitamin D insufficiency despite oral vitamin D supplementation. Here, we studied
      whether narrow-band ultraviolet B (NB-UVB) exposures improve vitamin D balance.
      METHODS: 14 haemodialysis patients and 15 healthy subjects receiving oral
      cholecalciferol 20 ug daily got nine NB-UVB exposures on the entire body. Serum
      25-hydroxyvitamin D (25(OH)D) was measured by radioimmunoassay. Cutaneous mRNA
      expression levels of CYP27A1 and CYP27B1, two enzymes required for hydroxylation
      of vitamin D into its active metabolite, were also measured. RESULTS: The
      baseline serum 25(OH)D concentration was 57.6 +/- 18.2 nmol/l in the CKD patients
      and 74.3 +/- 14.8 nmol/l in the healthy subjects. The NB-UVB course increased
      serum 25(OH)D by 14.0 nmol/l (95% CI 8.7-19.5) and 17.0 nmol/l (CI 13.7-20.2),
      respectively. At baseline the CKD patients showed significantly increased CYP27B1
      levels compared to the healthy subjects. CONCLUSIONS: A short NB-UVB course is an
      efficient way to improve vitamin D balance in CKD patients on dialysis who are
      receiving oral vitamin D supplementation. The increased cutaneous CYP27B1 levels
      in the CKD patients suggest that the loss of renal activity of this enzyme is at
      least partially compensated for by the skin.

PMID- 24029863
TI  - European Society of Hypertension position paper on ambulatory blood pressure
      monitoring.
AB  - Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both
      clinical practice and hypertension research. Although there are many guidelines
      that emphasize the indications for ABPM, there is no comprehensive guideline
      dealing with all aspects of the technique. It was agreed at a consensus meeting
      on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive
      position paper on the scientific evidence for ABPM.This position paper considers
      the historical background, the advantages and limitations of ABPM, the threshold
      levels for practice, and the cost-effectiveness of the technique. It examines the
      need for selecting an appropriate device, the accuracy of devices, the additional
      information and indices that ABPM devices may provide, and the software
      requirements.At a practical level, the paper details the requirements for using
      ABPM in clinical practice, editing considerations, the number of measurements
      required, and the circumstances, such as obesity and arrhythmias, when particular
      care needs to be taken when using ABPM.The clinical indications for ABPM, among
      which white-coat phenomena, masked hypertension, and nocturnal hypertension
      appear to be prominent, are outlined in detail along with special considerations
      that apply in certain clinical circumstances, such as childhood, the elderly and
      pregnancy, and in cardiovascular illness, examples being stroke and chronic renal
      disease, and the place of home measurement of blood pressure in relation to ABPM
      is appraised.The role of ABPM in research circumstances, such as pharmacological
      trials and in the prediction of outcome in epidemiological studies is examined
      and finally the implementation of ABPM in practice is considered in relation to
      the issue of reimbursement in different countries, the provision of the technique
      by primary care practices, hospital clinics and pharmacies, and the growing role
      of registries of ABPM in many countries. 

PMID- 24029864
TI  - Prognostic impact of clinic and ambulatory blood pressure components in high-risk
      type 2 diabetic patients: the Rio de Janeiro Type 2 Diabetes Cohort Study.
AB  - BACKGROUND: The prognostic importance of tight clinic blood pressure (BP) control
      is controversial in diabetic patients. The objective was to investigate the
      prognostic impact of clinic and ambulatory BPs for cardiovascular morbidity and
      mortality in type 2 diabetes. METHODS: In a prospective cohort study, 565 type 2
      diabetic patients had clinical, laboratory and ambulatory BP monitoring (ABPM)
      data obtained at baseline and during follow-up. The primary endpoints were a
      composite of fatal and nonfatal cardiovascular events and all-cause mortality.
      Multivariable Cox survival and splines regression analyses assessed associations
      between each BP component [SBP, DBP and pulse pressure (PP)] and the endpoints.
      RESULTS: After a median follow-up of 5.75 years, 88 total cardiovascular events
      and 70 all-cause deaths occurred. After adjustments for cardiovascular risk
      factors, clinic SBP and DBPs were predictive of the composite endpoint but not of
      all-cause mortality, whereas all ambulatory BP components were predictors of both
      endpoints. Ambulatory systolic and PPs were the strongest predictors and achieved
      ambulatory BPs during follow-up improved risk prediction in relation to baseline
      values. When categorized at clinically relevant cut-off values, risk began only
      at clinic BPs at least 140/90 mmHg, whereas for ambulatory BPs it began at lower
      values (>=120/75 mmHg for the 24-h period). CONCLUSION: ABPM provides more
      valuable information regarding cardiovascular risk stratification than office BPs
      and should be performed, if possible, in every high-risk type 2 diabetic patient.
      Achieved 24-h ambulatory BPs less than 120/75 mmHg are associated with
      significant cardiovascular protection and, if confirmed by other studies, may be
      considered as BP treatment targets.

PMID- 24029865
TI  - Association of hypermagnesemia and blood pressure in the critically ill.
AB  - BACKGROUND: Although magnesium is important in the biology of blood pressure
      regulation, little clinical data exist on the association of hypermagnesemia and
      blood pressure. METHOD: We examined the association of hypermagnesemia and SBP in
      a cross-sectional study of 10 521 ICU patients from a single tertiary care
      medical center, 6% of whom had a serum magnesium above 2.6 mg/dl at time of
      admission. RESULTS: In a multivariable analysis, hypermagnesemia was associated
      with SBP 6.2 mmHg lower [95% confidence interval (CI) -8.2, -4.2, P < 0.001] than
      in patients with admission values of serum magnesium 2.6 mg/dl or less. Each
      mg/dl increase in serum magnesium was associated with a decrease in SBP of 4.3
      mmHg (95% CI -5.5, -3.1, P < 0.001). In addition, hypermagnesemic patients had a
      2.48-fold greater likelihood (95% CI 2.06, 3.00, P < 0.001) of receiving
      intravenous vasopressors during the first 24 h of ICU care, independent of
      admission SBP. CONCLUSION: Our findings add support to the biologic importance of
      magnesium regulation in blood pressure control.

PMID- 24029866
TI  - Altered iron homeostasis in an animal model of hypertensive nephropathy: stroke
      prone rats.
AB  - BACKGROUND AND AIM: Iron is the most abundant metal in mammalian cells, and plays
      a pivotal role in many metabolic processes. Dysregulated iron homeostasis is
      involved in the cause of a number of pathological processes including renal
      diseases. METHODS AND RESULTS: Longitudinal MRI scans of salt-loaded
      spontaneously hypertensive stroke-prone rats (SHRSP), an animal model that
      spontaneously develops hypertensive nephropathy, showed a decrease in renal and
      hepatic T2 SI (a sign of iron accumulation) of, respectively, 42.3 +/- 2.5% (P <
      0.01) and 60.4 +/- 15.1% (P < 0.01) in comparison with SHRSP fed a standard diet.
      This was accompanied by the development of renal inflammation and oxidative
      stress (as evaluated by immunohistochemical and proteomic analyses),
      mitochondrial dysfunction, massive proteinuria and sustained intravascular
      hemolysis with the subsequent depletion of plasma haptoglobin, which was
      responsible for the renal uptake of hemoglobin and iron accumulation. In order to
      investigate the role of iron in these pathological processes, we subcutaneously
      treated the salt-loaded rats with the iron chelator deferoxamine (200 mg/kg per
      day). The pharmacological treatment prevented iron tissue accumulation, as
      indicated by the increase in renal and hepatic T2 SI of, respectively, 120.0 +/-
      10.1% (P < 0.01) and 73.9 +/- 4.4% (P < 0.01) in comparison with salt-loaded rats
      treated with vehicle alone. Deferoxamine also preserved renal morphology and
      function, the renal infiltration of ED-1-positive macrophages/monocytes, and the
      expression of MCP-1 and TGF-beta mRNA, reduced the level of reactive oxygen
      species, and improved the activity of mitochondrial cytochrome c oxidase.
      CONCLUSION: These findings suggest that iron dysmetabolism is involved in the
      development of hypertensive nephropathy in SHRSP.

PMID- 24029867
TI  - Hypertension in pregnancy is associated with elevated C-reactive protein levels
      later in life.
AB  - OBJECTIVES: We assessed whether hypertension in pregnancy is associated with
      elevated C-reactive protein (CRP) levels in later life, possibly reflecting an
      increased risk of cardiovascular disease (CVD). BACKGROUND: Elevated CRP levels
      have been associated with hypertension in pregnancy and with CVD. METHODS: We
      studied 2463 women from the Genetic Epidemiology Network of Arteriopathy (GENOA)
      study. Participants were categorized as nulliparous women (n = 219), women with a
      history of normotensive pregnancies (n = 1839), or women with a history of a
      hypertensive pregnancy (n = 405). Using multiple linear regression models, we
      compared mean CRP levels among the groups after adjusting for age, race,
      education, smoking, hypertension, personal history of coronary heart disease
      (CHD) or stroke, diabetes, dyslipidemia, statins, hormone replacement therapy,
      and family history of CHD or stroke. As CRP levels may be influenced by BMI, the
      model was fit both with and without adjusting for BMI. RESULTS: There was no
      significant difference in CRP levels between nulliparous women and those with a
      history of normotensive pregnancies, either with (P = 0.82) or without (P = 0.46)
      adjusting for BMI. In contrast, women with hypertensive pregnancies, compared
      with those with normotensive pregnancies, had higher CRP levels, both with (P =
      0.009) and without (P < 0.001) adjusting for BMI. CONCLUSION: A history of
      hypertension in pregnancy is associated with elevated CRP levels later in life,
      independent of traditional CVD risk factors and BMI. An elevated CRP may reflect
      an inflammatory state in women with a history of hypertensive pregnancy disorders
      who are at increased risk for CVD.

PMID- 24029868
TI  - Lack of age-related increase in carotid artery wall viscosity in
      cardiorespiratory fit men.
AB  - OBJECTIVES: Age-related arterial stiffening and reduction of arterial elasticity
      are attenuated in individuals with high levels of cardiorespiratory fitness.
      Viscosity is another mechanical characteristic of the arterial wall; however, the
      effects of age and cardiorespiratory fitness have not been determined. We
      examined the associations among age, cardiorespiratory fitness and carotid
      arterial wall viscosity. METHODS: A total of 111 healthy men, aged 25-39 years
      (young) and 40-64 years (middle-aged), were divided into either cardiorespiratory
      fit or unfit groups on the basis of peak oxygen uptake. The common carotid artery
      was measured noninvasively by tonometry and automatic tracking of B-mode images
      to obtain instantaneous pressure and diameter hysteresis loops, and we calculated
      the effective compliance, isobaric compliance and viscosity index. RESULTS: In
      the middle-aged men, the viscosity index was larger in the unfit group than in
      the fit group (2533 vs. 2018 mmHg.s/mm, respectively: P<0.05), but this was not
      the case in the young men. In addition, effective and isobaric compliance were
      increased, and viscosity index was increased with advancing age, but these
      parameters were unaffected by cardiorespiratory fitness level. CONCLUSION: These
      results suggest that the wall viscosity in the central artery is increased with
      advancing age and that the age-associated increase in wall viscosity may be
      attenuated in cardiorespiratory fit men.

PMID- 24029869
TI  - Night-time blood pressure is associated with the development of chronic kidney
      disease in a general population: the Ohasama Study.
AB  - OBJECTIVE: Ambulatory blood pressure (BP) is reportedly associated with target
      organ damage. However, whether ambulatory BP carries prognostic significance for
      the development of chronic kidney disease (CKD) has not been confirmed. METHOD:
      We measured ambulatory BP in 843 participants without CKD at baseline from a
      general Japanese population and examined the incidence of CKD defined as positive
      proteinuria or an estimated glomerular filtration rate (eGFR) less than 60 ml/min
      per 1.73 m at health checks. The association between baseline ambulatory BP and
      CKD incidence was examined using the Cox proportional hazard regression model
      adjusted for sex, age, BMI, habitual smoking, habitual alcohol consumption,
      diabetes mellitus, hypercholesterolemia, a history of cardiovascular disease,
      antihypertensive medication, eGFR at baseline, the number of follow-up
      examinations, and the year of the baseline examination. RESULTS: The mean age of
      the participants averaged 62.9 +/- 8.1 years, 71.3% were women and 23.7% were
      under antihypertensive medication. During a median follow-up of 8.3 years, 220
      participants developed CKD events. The adjusted hazard ratios for CKD in a 1
      standard deviation increase in daytime and night-time SBP were 1.13 [95%
      confidence interval (CI) 0.97-1.30] and 1.21 (95% CI 1.04-1.39), respectively.
      When night-time and daytime BP was mutually adjusted into the same model, only
      night-time BP persisted as an independent predictor of CKD. CONCLUSION: Night
      time BP is a better predictor of CKD development than daytime BP in the general
      population. Ambulatory BP measurement is considered useful for evaluating the
      risk of progression to CKD.

PMID- 24029870
TI  - African Caribbeans have greater subclinical cerebrovascular disease than
      Europeans: this is associated with both their elevated resting and ambulatory
      blood pressure and their hyperglycaemia.
AB  - OBJECTIVES: Stroke is elevated in people of black African descent, but evidence
      for excess subclinical cerebrovascular disease is conflicting, and the role of
      risk factors in determining any ethnic differences observed unexplored. METHODS:
      We compared prevalence of brain infarcts, and severe white matter
      hyperintensities (WMHs) on cerebral MRI, in a community-based sample of men and
      women aged 58-86 of African Caribbean (214) and European (605) descent, in
      London, UK. Resting, central and ambulatory blood pressure (BP) were measured;
      diabetes was assessed by blood testing and questionnaire. RESULTS: Mean age was
      70. Multiple (>=4) brain infarcts and severe WMH occurred more frequently in
      African Caribbeans (18/43%), than Europeans (7/33%, P=0.05/0.008). Separately,
      clinic and night-time ambulatory BP were significantly associated with severe WMH
      in both ethnic groups; when both were entered into the model, the association for
      clinic SBP was attenuated and lost statistical significance [1.00 (0.98-1.02)
      P=0.9 in Europeans, 1.00 (0.97-1.04) P=0.9 in African Caribbeans], whereas the
      association for night-time SBP was retained [1.04 (1.02-1.07) P<0.001 in
      Europeans, 1.08 (1.03-1.12), P=0.001 in African Caribbeans]. The greater age
      adjusted and sex-adjusted risk of severe WMH in African Caribbeans compared with
      Europeans [2.08 (1.15-3.76) P=0.02], was attenuated to 1.45 [(0.74-2.83) P=0.3]
      on adjustment for clinic and night-time systolic pressure, antihypertensive
      medication use and glycated haemoglobin. CONCLUSION: African Caribbeans have a
      greater burden of subclinical cerebrovascular disease than Europeans. This excess
      is related to elevated clinic and ambulatory BP, and to hyperglycaemia.

PMID- 24029871
TI  - Sodium restriction on top of renin-angiotensin-aldosterone system blockade
      increases circulating levels of N-acetyl-seryl-aspartyl-lysyl-proline in chronic
      kidney disease patients.
AB  - OBJECTIVE: Sodium restriction potentiates the efficacy of the rennin-angiotensin
      aldosterone system (RAAS)-blockade and improves long-term cardiovascular and
      renal protection, even independent of the better blood pressure control. The
      mechanisms underlying the potentiation of cardiorenal protection by sodium
      restriction are incompletely understood. RAAS-blockade with angiotensin
      converting enzyme (ACE) inhibitors increases circulating levels of the anti
      inflammatory and antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline
      (AcSDKP), which is assumed to contribute to its therapeutic effects. We
      hypothesized that sodium restriction on top of RAAS-blockade further increases
      AcSDKP, as a possible explanation for the enhanced effects of RAAS-blockade
      during sodium restriction. METHODS: To test this hypothesis, we performed a
      secondary analysis of a randomized clinical trial investigating 46 nondiabetic
      chronic kidney disease (CKD) patients (age 50+/-13 years, 80% men) with overt
      proteinuria and mild to moderate renal insufficiency. Patients were subjected, in
      a crossover design, to four double-blind 6-week study periods with either regular
      sodium diet (194+/-49 mmol Naday) or low sodium diet (102+/-52 mmol Na/day) on
      top of either lisinopril (40 mg/day; single RAAS-blockade) or lisinopril plus
      valsartan (320 mg/day; dual RAAS-blockade). RESULTS: Sodium restriction
      significantly increased circulating levels of AcSDKP during single and dual RAAS
      blockade (P=0.032 and 0.042, respectively). Linear mixed-model analysis confirmed
      that AcSDKP levels were increased in response to sodium restriction, irrespective
      of sex, age, creatinine clearance, blood pressure, BMI, single or dual RAAS
      blockade, treatment sequence and other dietary factors, that is calcium and
      protein (P=0.020). CONCLUSION: In patients with nondiabetic CKD, we demonstrated
      that sodium restriction, on top of single and dual RAAS-blockade, increases
      circulating levels of the anti-inflammatory and antifibrotic peptide AcSDKP. The
      rise in AcSDKP may contribute to the increased protection of RAAS-blockade during
      sodium restriction.

PMID- 24029872
TI  - Does a nondipping pattern influence left ventricular and left atrial mechanics in
      hypertensive patients?
AB  - OBJECTIVE: The aim of this study was to determine left ventricular and left
      atrial function in untreated hypertensive patients with different blood pressure
      (BP) patterns by using two-dimensional echocardiography (2DE) and three
      dimensional echocardiography (3DE) speckle tracking analyses. METHODS: This cross
      sectional study included 147 recently diagnosed hypertensive patients (86 dippers
      and 61 nondippers). All patients underwent a 24-h ambulatory BP monitoring and
      complete 2DE and 3DE examination including speckle tracking analysis. RESULTS:
      The analysis of our results showed that 3DE left ventricular global longitudinal
      strain was significantly lower in the nondippers (-17.8 +/- 2.6 vs. -16.2 +/-
      2.4%, P < 0.001). Similar results were obtained for 3DE left ventricular global
      circumferential strain (-17.4 +/- 2.7 vs. -16.3 +/- 2.6%, P = 0.015), as well for
      3DE left ventricular global radial strain (45.8 +/- 8.5 vs. 42.1 +/- 8.2%, P =
      0.009), and left ventricular global area strain (-29.1 +/- 4.7 vs. -27.4 +/-
      4.3%, P = 0.027). The left ventricular twist was increased in the nondippers
      (12.7 +/- 2.9 vs. 14.1 +/- 3.4 degrees , P = 0.008), whereas the untwisting rate
      was significantly decreased in this group (-43.7 +/- 5.7 vs. -36.9 +/- 5.1 
      degrees /s, P < 0.001). The left atrial longitudinal strain, as well as left
      atrial systolic and early diastolic strain rates, was decreased in nondippers.
      Independent predictors of 3DE left ventricular longitudinal, circumferential,
      radial, and area strain were a 24-h mean BP, (E/e')m, and 3DE left ventricular
      ejection fraction. An additional independent predictor of the left atrial
      longitudinal strain was 3DE left ventricular mass index. CONCLUSION: The 3DE
      speckle tracking examination demonstrated that the left ventricular and left
      atrial mechanics were more impaired in the nondippers than in the dippers
      untreated hypertensive patients.

PMID- 24029873
TI  - Heritability analyses show visit-to-visit blood pressure variability reflects
      different pathological phenotypes in younger and older adults: evidence from UK
      twins.
AB  - BACKGROUND: Clinic and long-term average blood pressure (BP) are heritable traits
      with estimates of heritability ranging from 0.31 to 0.68. Long-term visit-to
      visit BP variability (BPV) is emerging as a new cardiovascular risk predictor,
      though it is unclear if this is completely independent of BP. We hypothesize that
      BPV should demonstrate the same pattern of additive genetic, shared environmental
      and unique environmental variance as BP, if both are phenotypic surrogates.
      METHOD: We studied 2889 twin pairs not on any BP-lowering therapy from the Twins
      UK cohort, and estimated the additive genetic variance for baseline BP, long-term
      average BP, BP trajectory (rate of change of BP in mmHg/year) and BPV
      (coefficient of variation and average real variability over an average of 3.2
      visits). Heritability estimates were obtained by structural equation modelling
      adjusting for age, age, sex and BMI. RESULTS: The heritabilities for baseline SBP
      and DBP were 0.51 (95% confidence interval 0.49, 0.53) and 0.56 (0.54, 0.58);
      long-term average SBP and DBP were 0.56 (0.53, 0.59) and 0.61 (0.58, 0.64); and
      systolic and diastolic trajectories over 10 years were 0.49 (0.46, 0.52) and 0.29
      (0.27, 0.32), respectively. Both overall systolic and diastolic BPV showed no
      additive genetic variance contributing to the phenotypic variation, but after
      stratification by age, the younger subgroup (<51 years) showed heritability
      estimates of 0.44 (0.38, 0.50) for coefficient of variation and 0.35 (0.29, 0.41)
      for average real variability. CONCLUSION: Age is a major factor that influences
      heritability estimation of BPV and it is likely that BPV in younger and older age
      groups may reflect different pathological phenotypes.

PMID- 24029874
TI  - Long-term alcohol consumption is an independent risk factor of hypertension
      development in northern China: evidence from Kailuan study.
AB  - OBJECTIVE: The purpose of the present study was to determine the impact of
      alcohol consumption on the incidence of hypertension. METHODS: A total of 32,389
      male coal mine workers from Kailuan Coal Group in northern China (Kailuan study),
      free of hypertension, myocardial infarction, stroke, transient ischemia attack
      and cancer, were followed up every 2 years for 4 years. The average alcohol
      intake during the past year was reported as baseline. RESULTS: During 4 years of
      follow-up, 9151 out of 32,389 workers developed hypertension categorically. At
      the end of the follow-up, the cumulative incidence of hypertension in relation to
      daily alcoholic intake of none, 1-24, 25-49, 50-99, 100-149 and at least 150 g
      was 25.03, 28.82, 30.10, 37.07, 40.14 and 42.49%, respectively. After adjusting
      for age, we found that the relative risk of hypertension in those who were never
      exposed to alcohol was the lowest, with the group 25-49 g/day being the next.
      This trend was unchanged after adjustment for age, exercise, smoking status, job
      type and salt intake. After further adjustment for BMI, history of high
      cholesterol and diabetes mellitus, a positive, linear association between alcohol
      consumption and the risk of hypertension was found. Models stratified by baseline
      SBP (<120 and 120-139 mmHg) or DBP (<80 and 80-89 mmHg) did not alter the trend.
      CONCLUSION: The Kailuan study demonstrates that long-term alcohol intake is an
      independent risk factor of incident hypertension in a large cohort of coal mine
      workers. Even light-to-moderate alcohol consumption increases the risk of
      incident hypertension.

PMID- 24029875
TI  - Sol-gel conversion based on photoswitching between noncovalently and covalently
      linked netlike supramolecular polymers.
AB  - Photo-control over supramolecular sol-gel conversion is achieved by incorporating
      photoactive coumarin moieties into a tribranched monomer and the self-assembly
      with gamma-CD followed by noncovalent-covalent switchover. 

PMID- 24029876
TI  - Improvement of cell growth and L-lysine production by genetically modified
      Corynebacterium glutamicum during growth on molasses.
AB  - Fructose-1,6-bisphosphatase (FBPase) and fructokinase (ScrK) have important roles
      in regenerating glucose-6-phosphate in the pentose phosphate pathway (PPP), and
      thus increasing L-lysine production. This article focuses on the development of L
      lysine high-producing strains by heterologous expression of FBPase gene fbp and
      ScrK gene scrK in C. glutamicum lysC (fbr) with molasses as the sole carbon
      source. Heterologous expression of fbp and scrK lead to a decrease of residual
      sugar in fermentation broth, and heterologous expression of scrK prevents the
      fructose efflux. Heterologous expression of fbp and scrK not only increases
      significantly the activity of corresponding enzymes but also improves cell growth
      during growth on molasses. FBPase activities are increased tenfold by
      heterologous expression of fbp, whereas the FBPase activity is only increase
      fourfold during co-expression of scrK and fbp. Compared with glucose, the DCW of
      heterologous expression strains are higher on molasses except co-expression of
      fbp and scrK strain. In addition, heterologous expression of fbp and scrK can
      strongly increase the L-lysine production with molasses as the sole carbon
      source. The highest increase (88.4 %) was observed for C. glutamicum lysC (fbr)
      pDXW-8-fbp-scrK, but the increase was also significant for C. glutamicum lysC
      (fbr) pDXW-8-fbp (47.2 %) and C. glutamicum lysC (fbr) pDXW-8-scrK (36.8 %). By
      products, such as glycerol and dihydroxyacetone, are decreased by heterologous
      expression of fbp and scrK, whereas trehalose is only slightly increased. The
      strategy for enhancing L-lysine production by regeneration of glucose-6-phosphate
      in PPP may provide a reference to enhance the production of other amino acids
      during growth on molasses or starch. 

PMID- 24029877
TI  - SIRT4 prevents hypoxia-induced apoptosis in H9c2 cardiomyoblast cells.
AB  - AIMS: Apoptosis plays a critical role in cardiomyocyte loss during ischaemic
      heart injury. A detailed understanding of the mechanism involved has a
      substantial impact on the optimization and development of treatment strategies.
      Here, we report that the expression of SIRT4, a mitochondrial sirtuin, is
      markedly down-regulated in hypoxia-induced apoptosis of H9c2 cardiomyoblast
      cells. METHODS AND RESULTS: SIRT4 interference significantly alters H9c2 cell
      viability, apoptotic cell number and caspase-3/7 activity. Furthermore, SIRT4
      expression can affect the ratio of pro-caspase 9/caspase 9 or pro-caspase
      3/caspase 3, an affect Bax translocation, which in turn alters the development of
      H9c2 cell apoptosis. CONCLUSION: These results suggest that SIRT4 is a key player
      in hypoxia-induced cardiomyocyte apoptosis, and that strategies based on its
      enhancement might be of benefit in the treatment of ischaemic heart disease.

PMID- 24029879
TI  - Micro-analysis by near-infrared diffuse reflectance spectroscopy with chemometric
      methods.
AB  - Great attention has been paid to near-infrared diffuse reflectance spectroscopy
      (NIRDRS) due to its practicability in analyzing real complex samples. However,
      the application of the technique in micro-analysis is badly restricted by its low
      sensitivity or high detection limit. In this study, the possibility of achieving
      the sensitive detection of micro-components using NIRDRS with the help of
      chemometric methods is studied with two experimental datasets. The results show
      that a very high sensitivity can be obtained when the noise and the variant
      background are minimized. Quantitative determination of low concentrations of
      pesticides and trace Cr(3+) in solutions is achieved by using preconcentration
      and chemometric approaches to minimize the noise and background. The absolute
      prediction error of the method can be as low as 7.6 MUg for the pesticide and
      28.6 MUg for Cr(3+). These quantities are equivalent to 76 ng mL(-1) and 286 ng
      mL(-1) if 100 mL of solution are used for the analysis. 

PMID- 24029878
TI  - Quantitative full time course analysis of nonlinear enzyme cycling kinetics.
AB  - Enzyme inhibition due to the reversible binding of reaction products is common
      and underlies the origins of negative feedback inhibition in many metabolic and
      signaling pathways. Product inhibition generates non-linearity in steady-state
      time courses of enzyme activity, which limits the utility of well-established
      enzymology approaches developed under the assumption of irreversible product
      release. For more than a century, numerous attempts to find a mathematical
      solution for analysis of kinetic time courses with product inhibition have been
      put forth. However, no practical general method capable of extracting common
      enzymatic parameters from such non-linear time courses has been successfully
      developed. Here we present a simple and practical method of analysis capable of
      efficiently extracting steady-state enzyme kinetic parameters and product binding
      constants from non-linear kinetic time courses with product inhibition and/or
      substrate depletion. The method is general and applicable to all enzyme systems,
      independent of reaction schemes and pathways. 

PMID- 24029880
TI  - Decreasing radiation exposure on pediatric portable chest radiographs.
AB  - PURPOSE: To determine whether additional shielding designed for pediatric
      patients during portable chest exams that ascertain endotracheal tube placement
      would significantly decrease the amount of scatter radiation. METHODS: Children
      aged 24 months or younger were intubated and received daily morning chest
      radiographs to determine endotracheal tube placement. RESULTS: For each
      measurement, the amount of scatter radiation decreased by more than 20% from a
      nonshielded exposure to a shielded exposure. DISCUSSION: There was a significant
      decrease in scatter radiation when using the lead shielding device along with
      appropriate collimation vs appropriate collimation alone. CONCLUSION: These
      results suggest that applying additional shielding to appropriately collimated
      chest radiographs could significantly reduce scatter radiation and therefore the
      overall dose to young children.

PMID- 24029881
TI  - E-tutorial improves students' ability to detect lesions.
AB  - PURPOSE: This Australian study explores the effects of an educational
      intervention on first-year medical radiation sciences (MRS) students by examining
      eye-tracking metrics while they attempted to detect breast lesions on radiologic
      images before and after an e-learning tutorial. The study also analyzes
      performance using receiver operating characteristic methodology. METHODS:
      Fourteen first-year MRS students were equally and randomly assigned to a control
      or experiment group to participate in 2 image-detection sessions. The experiment
      group completed an online e-learning tutorial between sessions. Eighty
      mammographic breast images from 20 cases were obtained from a validated online
      image bank. Of those 20 cases, 30% were normal and 70% demonstrated a single
      lesion abnormality. RESULTS: The experiment group demonstrated a 45% increase in
      the mean number of fixations per case (P = .047), with a 30% increase in
      sensitivity (P = .022) following the tutorial. The experiment group also
      demonstrated improved lesion detection overall and a 49% decrease in mean time to
      first fixation on the lesion (P = .016). DISCUSSION: This study demonstrates that
      increased lesion detection is possible after a brief e-learning tutorial. Early
      changes in the viewing patterns of less-experienced technologists are intriguing,
      and explanation may be gained from our current understanding of radiologic
      perception and cognitive neuroscience. The task for the first-year MRS students
      in this study was only to positively detect a lesion, and we recognize that a
      higher level of visual processing would be required to critique image quality.
      Exposure to the brief tutorial, however, might have triggered some learning
      related neural changes at an early level of visual processing, representing
      stimuli relating to task performance. CONCLUSION: Participants in the experiment
      group improved their ability to identify breast lesions, which coincided with
      changes in eye position metrics and error type analysis. The data presented here
      suggest that the intervention resulted in a significant improvement in detection
      by the experiment group.

PMID- 24029882
TI  - Online course delivery modes and design methods in the radiologic sciences.
AB  - PURPOSE: To determine the current status of online education in the radiologic
      sciences and to explore learning management systems, course design methods, and
      online educational tools used in the radiologic sciences. METHODS: A random
      sample of 373 educators from Joint Review Committee-accredited radiography,
      radiation therapy, and nuclear medicine technology educational programs was
      invited to participate in this study with an online survey. RESULTS: The majority
      of the programs responding to the survey do not offer online core courses.
      However, the institutions that do provide online core radiologic courses reported
      limited use of online tools for course delivery. BlackBoard was reported as the
      most commonly used learning management system. No significant relationships were
      identified in reference to self-reported instructor information technology self
      efficacy and the instructors' age, years of teaching in higher education, years
      of teaching online, or use of asynchronous and synchronous technologies. Survey
      results did demonstrate a significant relationship between the type of
      institution and the use of synchronous technologies, suggesting that university
      based programs were more likely to use this technology. DISCUSSION: Although the
      results suggest that online distance education is still not prevalent in
      radiologic science education, the past 3 years have seen a substantial increase
      in online course activity. This increase emphasizes the importance of adequate
      educator instruction and continuing education in the use of interactive
      technologies for online content delivery. Most educators report receiving 1 to 4
      hours of training prior to online course implementation, but additional
      postimplementation training is necessary to improve the success of online
      delivery and further integrate interactive learning activities into an online
      format. CONCLUSION: The traditional classroom setting is still the primary course
      offering for radiologic science programs. PowerPoint remains the primary content
      delivery tool, suggesting a need for educators to incorporate tools that promote
      student interactions and interactive learning. Although the results did not
      reveal a significant relationship between assessed factors, the small
      correlations identified suggest that the younger instructors have a higher
      information technology self-efficacy. In addition, survey results suggest that
      instructors responding to this survey received limited training in reference to
      online course methods and design both before and after implementing an online
      course. Although educators may not have a choice regarding the system adopted by
      their university or college, they should seek additional training regarding the
      best tools available for online course delivery methods.

PMID- 24029883
TI  - Women and heart disease.
AB  - Heart disease is known more as a killer of men than women, but U.S. women have
      surpassed men in prevalence of and mortality from cardiovascular diseases.
      Although recent years have witnessed an upswing in education, awareness, and
      clinical research focused on heart disease in women, much work remains to reach a
      sufficient understanding of the differences in risk, presentation, and management
      of heart disease between the sexes to improve outcomes for women. Medical imaging
      has enhanced diagnosis and management of heart disease in women, especially by
      enabling less invasive approaches. 

PMID- 24029884
TI  - Substance abuse and the radiologic technologist.
AB  - Radiologic technologists, like other health care professionals, are at risk for
      substance abuse and addiction. Substance abuse can have grave consequences for
      technologists, their patients, and their employers, and all technologists should
      be alert to the problem and prepared to address it. This article defines
      substance use terminology, identifies commonly abused substances and their
      effects, describes risk factors for substance abuse, and discusses possible signs
      of impairment. Radiologic technologists are reminded of their ethical
      responsibilities regarding substance use, and substance abuse treatment and
      prevention are addressed. 

PMID- 24029885
TI  - Shared experience: additional guidelines.

PMID- 24029886
TI  - Shared experience: the author responds.

PMID- 24029887
TI  - Shared experience: management strategies.

PMID- 24029888
TI  - Shared experience: stress management.

PMID- 24029889
TI  - Shared experience: the author responds.

PMID- 24029890
TI  - WebQuests can supplement student learning of radiographic anatomy.

PMID- 24029891
TI  - Writing a country report for use in radiology outreach initiatives.

PMID- 24029892
TI  - Investigating orthogonal radiography in the diagnosis of radial head fractures.

PMID- 24029893
TI  - Carotid vessel evaluation via a 3-D workstation.

PMID- 24029894
TI  - Mammography rotations for all students: how to make it work.

PMID- 24029896
TI  - Separation anxiety.

PMID- 24029895
TI  - Delayed energy release by selenium-based detectors.

PMID- 24029897
TI  - Breast density and digital breast tomosynthesis.
AB  - Dense breast tissue has been linked to an increased risk of breast cancer. This
      is partly a result of difficulties in detecting cancer in dense breasts using
      conventional mammography. Digital breast tomosynthesis (DBT) is an alternative
      imaging modality that has shown high sensitivity in dense breast tissue. Because
      of its 3-D capability, DBT allows more accurate viewing of dense breast tissue by
      eliminating the overlapping effect associated with 2-D imaging. Although DBT has
      certain disadvantages, support for DBT is increasing among health care
      professionals, researchers, and patients. 

PMID- 24029898
TI  - The zinc transporter ZnT8 (slc30A8) is expressed exclusively in beta cells in
      porcine islets.
AB  - Diabetes represents a major endemic disease throughout the world, and different
      therapeutic methods are used to treat the disease. Xenotransplantation of pig
      islet cells is a potential treatment for type 1 diabetes, but studies of protein
      expression in distinct islet cells are rare. ZnT8, a member of the slc30A gene
      family, is involved in islet endocrine hormone release and is a diabetes auto
      antigen, raising the question of whether ZnT8 expression is regulated similarly
      in pig and human pancreas. We used nested RT-PCR to detect ZnT8 expression in pig
      pancreas and polyclonal antibody to examine possible co-localization with other
      islet hormones. Immunohistochemistry of sequential serial sections as well as
      double immunostaining of pancreatic tissues with antibodies against ZnT8,
      insulin, glucagon, and somatostatin shows that pig ZnT8 is exclusively co
      expressed in insulin-producing, but not in glucagon- or somatostatin-producing
      cells. The absence of ZnT8 in glucagon-producing cells in pig islets indicates
      that zinc homeostasis is mediated by a different cellular mechanism compared with
      human islet cells. Our findings provide important information about the cell-type
      specific expression of ZnT8 in porcine islet cells, which should be taken into
      account when evaluating different xenotransplantation approaches. 

PMID- 24029899
TI  - Contextual cueing impairment in patients with age-related macular degeneration.
AB  - Visual attention can be guided by past experience of regularities in our visual
      environment. In the contextual cueing paradigm, incidental learning of repeated
      distractor configurations speeds up search times compared to random search
      arrays. Concomitantly, fewer fixations and more direct scan paths indicate more
      efficient visual exploration in repeated search arrays. In previous work, we
      found that simulating a central scotoma in healthy observers eliminated this
      search facilitation. Here, we investigated contextual cueing in patients with age
      related macular degeneration (AMD) who suffer from impaired foveal vision. AMD
      patients performed visual search using only their more severely impaired eye (n =
      13) as well as under binocular viewing (n = 16). Normal-sighted controls
      developed a significant contextual cueing effect. In comparison, patients showed
      only a small nonsignificant advantage for repeated displays when searching with
      their worse eye. When searching binocularly, they profited from contextual cues,
      but still less than controls. Number of fixations and scan pattern ratios showed
      a comparable pattern as search times. Moreover, contextual cueing was
      significantly correlated with acuity in monocular search. Thus, foveal vision
      loss may lead to impaired guidance of attention by contextual memory cues.

PMID- 24029900
TI  - Anisotropic sampling of planar and two-manifold domains for texture generation
      and glyph distribution.
AB  - We present a new method for the generation of anisotropic sample distributions on
      planar and two-manifold domains. Most previous work that is concerned with
      aperiodic point distributions is designed for isotropically shaped samples.
      Methods focusing on anisotropic sample distributions are rare, and either they
      are restricted to planar domains, are highly sensitive to the choice of
      parameters, or they are computationally expensive. In this paper, we present a
      time-efficient approach for the generation of anisotropic sample distributions
      that only depends on intuitive design parameters for planar and two-manifold
      domains. We employ an anisotropic triangulation that serves as basis for the
      creation of an initial sample distribution as well as for a gravitational
      centered relaxation. Furthermore, we present an approach for interactive
      rendering of anisotropic Voronoi cells as base element for texture generation. It
      represents a novel and flexible visualization approach to depict metric tensor
      fields that can be derived from general tensor fields as well as scalar or vector
      fields. 

PMID- 24029901
TI  - Automatic paper sliceform design from 3D solid models.
AB  - A paper sliceform or lattice-style pop-up is a form of papercraft that uses two
      sets of parallel paper patches slotted together to make a foldable structure. The
      structure can be folded flat, as well as fully opened (popped-up) to make the two
      sets of patches orthogonal to each other. Automatic design of paper sliceforms is
      still not supported by existing computational models and remains a challenge. We
      propose novel geometric formulations of valid paper sliceform designs that
      consider the stability, flat-foldability and physical realizability of the
      designs. Based on a set of sufficient construction conditions, we also present an
      automatic algorithm for generating valid sliceform designs that closely depict
      the given 3D solid models. By approximating the input models using a set of
      generalized cylinders, our method significantly reduces the search space for
      stable and flat-foldable sliceforms. To ensure the physical realizability of the
      designs, the algorithm automatically generates slots or slits on the patches such
      that no two cycles embedded in two different patches are interlocking each other.
      This guarantees local pairwise assembility between patches, which is empirically
      shown to lead to global assembility. Our method has been demonstrated on a number
      of example models, and the output designs have been successfully made into real
      paper sliceforms. 

PMID- 24029902
TI  - Change blindness images.
AB  - Change blindness refers to human inability to recognize large visual changes
      between images. In this paper, we present the first computational model of change
      blindness to quantify the degree of blindness between an image pair. It comprises
      a novel context-dependent saliency model and a measure of change, the former
      dependent on the site of the change, and the latter describing the amount of
      change. This saliency model in particular addresses the influence of background
      complexity, which plays an important role in the phenomenon of change blindness.
      Using the proposed computational model, we are able to synthesize changed images
      with desired degrees of blindness. User studies and comparisons to state-of-the
      art saliency models demonstrate the effectiveness of our model. 

PMID- 24029903
TI  - GosperMap: using a Gosper Curve for laying out hierarchical data.
AB  - The emergence of very large hierarchies that result from the increase in
      available data raises many problems of visualization and navigation. On data sets
      of such scale, classical graph drawing methods do not take advantage of certain
      human cognitive skills such as shape recognition. These cognitive skills could
      make it easier to remember the global structure of the data. In this paper, we
      propose a method that is based on the use of nested irregular shapes. We name it
      GosperMap as we rely on the use of a Gosper Curve to generate these shapes. By
      employing human perception mechanisms that were developed by handling, for
      example, cartographic maps, this technique facilitates the visualization and
      navigation of a hierarchy. An algorithm has been designed to preserve region
      containment according to the hierarchy and to set the leaves' sizes
      proportionally to a property, in such a way that the size of nonleaf regions
      corresponds to the sum of their children's sizes. Moreover, the input ordering of
      the hierarchy's nodes is preserved, i.e., the areas that represent two
      consecutive children of a node in the hierarchy are adjacent to one another. This
      property is especially useful because it guarantees some stability in our
      algorithm. We illustrate our technique by providing visualization examples of the
      repartition of tax money in the US over time. Furthermore, we validate the use of
      the GosperMap in a professional documentation context and show the stability and
      ease of memorization for this type of map. 

PMID- 24029904
TI  - Hierarchical reorganization of dimensions in OLAP visualizations.
AB  - In this paper, we propose a new method for the visual reorganization of online
      analytical processing (OLAP) cubes that aims at improving their visualization.
      Our method addresses dimensions with hierarchically organized members. It uses a
      genetic algorithm that reorganizes k-ary trees. Genetic operators perform
      permutations of subtrees to optimize a visual homogeneity function. We propose
      several ways to reorganize an OLAP cube depending on which set of members is
      selected for the reorganization: all of the members, only the displayed members,
      or the members at a given level (level by level approach). The results that are
      evaluated by using optimization criteria show that our algorithm has a reliable
      performance even when it is limited to 1 minute runs. Our algorithm was
      integrated in an interactive 3D interface for OLAP. A user study was conducted to
      evaluate our approach with users. The results highlight the usefulness of
      reorganization in two OLAP tasks. 

PMID- 24029905
TI  - KelpFusion: a hybrid set visualization technique.
AB  - We present KelpFusion: a method for depicting set membership of items on a map or
      other visualization using continuous boundaries. KelpFusion is a hybrid
      representation that bridges hull techniques such as Bubble Sets and Euler
      diagrams and line- and graph-based techniques such as LineSets and Kelp Diagrams.
      We describe an algorithm based on shortest-path graphs to compute KelpFusion
      visualizations. Based on a single parameter, the shortest-path graph varies from
      the minimal spanning tree to the convex hull of a point set. Shortest-path graphs
      aim to capture the shape of a point set and smoothly adapt to sets of varying
      densities. KelpFusion fills enclosed faces based on a set of simple legibility
      rules. We present the results of a controlled experiment comparing KelpFusion to
      Bubble Sets and LineSets. We conclude that KelpFusion outperforms Bubble Sets
      both in accuracy and completion time and outperforms LineSets in completion time.

PMID- 24029906
TI  - Marker optimization for facial motion acquisition and deformation.
AB  - A long-standing problem in marker-based facial motion capture is what are the
      optimal facial mocap marker layouts. Despite its wide range of potential
      applications, this problem has not yet been systematically explored to date. This
      paper describes an approach to compute optimized marker layouts for facial motion
      acquisition as optimization of characteristic control points from a set of high
      resolution, ground-truth facial mesh sequences. Specifically, the thin-shell
      linear deformation model is imposed onto the example pose reconstruction process
      via optional hard constraints such as symmetry and multiresolution constraints.
      Through our experiments and comparisons, we validate the effectiveness,
      robustness, and accuracy of our approach. Besides guiding minimal yet effective
      placement of facial mocap markers, we also describe and demonstrate its two
      selected applications: marker-based facial mesh skinning and multiresolution
      facial performance capture. 

PMID- 24029907
TI  - Optimizing constrained-environment redirected walking instructions using search
      techniques.
AB  - A goal of redirected walking (RDW) is to allow large virtual worlds to be
      explored within small tracking areas. Generalized steering algorithms, such as
      steer-to-center, simply move the user toward locations that are considered to be
      collision free in most cases. The algorithm developed here, FORCE, identifies
      collision-free paths by using a map of the tracking area's shape and obstacles,
      in addition to a multistep, probabilistic prediction of the user's virtual path
      through a known virtual environment. In the present implementation, the path
      predictions describe a user's possible movements through a virtual store with
      aisles. Based on both the user's physical and virtual location / orientation, a
      search-based optimization technique identifies the optimal steering instruction
      given the possible user paths. Path prediction uses the map of the virtual world;
      consequently, the search may propose steering instructions that put the user
      close to walls if the user's future actions eventually lead away from the wall.
      Results from both simulated and real users are presented. FORCE identifies
      collision-free paths in 55.0 percent of the starting conditions compared to 46.1
      percent for generalized methods. When considering only the conditions that result
      in different outcomes, redirection based on FORCE produces collision-free path
      94.5 percent of the time. 

PMID- 24029908
TI  - SuperMatching: feature matching using supersymmetric geometric constraints.
AB  - Feature matching is a challenging problem at the heart of numerous computer
      graphics and computer vision applications. We present the SuperMatching algorithm
      for finding correspondences between two sets of features. It does so by
      considering triples or higher order tuples of points, going beyond the pointwise
      and pairwise approaches typically used. SuperMatching is formulated using a
      supersymmetric tensor representing an affinity metric that takes into account
      feature similarity and geometric constraints between features: Feature matching
      is cast as a higher order graph matching problem. SuperMatching takes advantage
      of supersymmetry to devise an efficient sampling strategy to estimate the
      affinity tensor, as well as to store the estimated tensor compactly. Matching is
      performed by an efficient higher order power iteration approach that takes
      advantage of this compact representation. Experiments on both synthetic and real
      data show that SuperMatching provides more accurate feature matching than other
      state-of-the-art approaches for a wide range of 2D and 3D features, with
      competitive computational cost. 

PMID- 24029909
TI  - The five Ws for information visualization with application to healthcare
      informatics.
AB  - The Five Ws is a popular concept for information gathering in journalistic
      reporting. It captures all aspects of a story or incidence: who, when, what,
      where, and why. We propose a framework composed of a suite of cooperating visual
      information displays to represent the Five Ws and demonstrate its use within a
      healthcare informatics application. Here, the who is the patient, the where is
      the patient's body, and the when, what, why is a reasoning chain which can be
      interactively sorted and brushed. The patient is represented as a radial sunburst
      visualization integrated with a stylized body map. This display captures all
      health conditions of the past and present to serve as a quick overview to the
      interrogating physician. The reasoning chain is represented as a multistage flow
      chart, composed of date, symptom, data, diagnosis, treatment, and outcome. Our
      system seeks to improve the usability of information captured in the electronic
      medical record (EMR) and we show via multiple examples that our framework can
      significantly lower the time and effort needed to access the medical patient
      information required to arrive at a diagnostic conclusion. 

PMID- 24029910
TI  - The sinogram polygonizer for reconstructing 3D shapes.
AB  - This paper proposes a novel approach, the sinogram polygonizer, for directly
      reconstructing 3D shapes from sinograms (i.e., the primary output from X-ray
      computed tomography (CT) scanners consisting of projection image sequences of an
      object shown from different viewing angles). To obtain a polygon mesh
      approximating the surface of a scanned object, a grid-based isosurface
      polygonizer, such as Marching Cubes, has been conventionally applied to the CT
      volume reconstructed from a sinogram. In contrast, the proposed method treats CT
      values as a continuous function and directly extracts a triangle mesh based on
      tetrahedral mesh deformation. This deformation involves quadratic error metric
      minimization and optimal Delaunay triangulation for the generation of accurate,
      high-quality meshes. Thanks to the analytical gradient estimation of CT values,
      sharp features are well approximated, even though the generated mesh is very
      coarse. Moreover, this approach eliminates aliasing artifacts on triangle meshes.

PMID- 24029911
TI  - Tiling motion patches.
AB  - Simulating multiple character interaction is challenging because character
      actions must be carefully coordinated to align their spatial locations and
      synchronized with each other. We present an algorithm to create a dense crowd of
      virtual characters interacting with each other. The interaction may involve
      physical contacts, such as hand shaking, hugging, and carrying a heavy object
      collaboratively. We address the problem by collecting deformable motion patches,
      each of which describes an episode of multiple interacting characters, and tiling
      them spatially and temporally. The tiling of motion patches generates a seamless
      simulation of virtual characters interacting with each other in a nontrivial
      manner. Our tiling algorithm uses a combination of stochastic sampling and
      deterministic search to address the discrete and continuous aspects of the tiling
      problem. Our tiling algorithm made it possible to automatically generate highly
      complex animation of multiple interacting characters. We achieve the level of
      interaction complexity far beyond the current state of the art that animation
      techniques could generate, in terms of the diversity of human behaviors and the
      spatial/temporal density of interpersonal interactions. 

PMID- 24029912
TI  - Video-based crowd synthesis.
AB  - As a controllable medium, video-realistic crowds are important for creating the
      illusion of a populated reality in special effects, games, and architectural
      visualization. While recent progress in simulation and motion captured-based
      techniques for crowd synthesis has focused on natural macroscale behavior, this
      paper addresses the complementary problem of synthesizing crowds with realistic
      microscale behavior and appearance. Example-based synthesis methods such as video
      textures are an appealing alternative to conventional model-based methods, but
      current techniques are unable to represent and satisfy constraints between video
      sprites and the scene. This paper describes how to synthesize crowds by
      segmenting pedestrians from input videos of natural crowds and optimally placing
      them into an output video while satisfying environmental constraints imposed by
      the scene. We introduce crowd tubes, a representation of video objects designed
      to compose a crowd of video billboards while avoiding collisions between static
      and dynamic obstacles. The approach consists of representing crowd tube samples
      and constraint violations with a conflict graph. The maximal independent set
      yields a dense constraint-satisfying crowd composition. We present a prototype
      system for the capture, analysis, synthesis, and control of video-based crowds.
      Several results demonstrate the system's ability to generate videos of crowds
      which exhibit a variety of natural behaviors.

PMID- 24029913
TI  - Visualizing the variability of gradients in uncertain 2D scalar fields.
AB  - In uncertain scalar fields where data values vary with a certain probability, the
      strength of this variability indicates the confidence in the data. It does not,
      however, allow inferring on the effect of uncertainty on differential quantities
      such as the gradient, which depend on the variability of the rate of change of
      the data. Analyzing the variability of gradients is nonetheless more complicated,
      since, unlike scalars, gradients vary in both strength and direction. This
      requires initially the mathematical derivation of their respective value ranges,
      and then the development of effective analysis techniques for these ranges. This
      paper takes a first step into this direction: Based on the stochastic modeling of
      uncertainty via multivariate random variables, we start by deriving uncertainty
      parameters, such as the mean and the covariance matrix, for gradients in
      uncertain discrete scalar fields. We do not make any assumption about the
      distribution of the random variables. Then, for the first time to our best
      knowledge, we develop a mathematical framework for computing confidence intervals
      for both the gradient orientation and the strength of the derivative in any
      prescribed direction, for instance, the mean gradient direction. While this
      framework generalizes to 3D uncertain scalar fields, we concentrate on the
      visualization of the resulting intervals in 2D fields. We propose a novel color
      diffusion scheme to visualize both the absolute variability of the derivative
      strength and its magnitude relative to the mean values. A special family of
      circular glyphs is introduced to convey the uncertainty in gradient orientation.
      For a number of synthetic and real-world data sets, we demonstrate the use of our
      approach for analyzing the stability of certain features in uncertain 2D scalar
      fields, with respect to both local derivatives and feature orientation. 

PMID- 24029914
TI  - Aquaporin-4 antibody-positive myelitis initially biopsied for suspected spinal
      cord tumors: diagnostic considerations.
AB  - Two patients with longitudinally extensive myelopathy were initially biopsied for
      suspected spinal cord tumors. Both patients were later diagnosed with
      neuromyelitis optica spectrum disorders (NMOSD) supported by their AQP4
      seropositivity. Pathological review of both biopsies revealed demyelinated
      lesions with thickened vessel walls and tissue rarefaction. Immunohistochemical
      staining demonstrated findings compatible with acute NMOSD lesions in one case
      while the other case exhibited findings consistent with chronic NMOSD lesions. A
      pre-biopsy differential diagnosis of longitudinally extensive spinal cord tumors
      should include NMOSD. Specific biopsy features, such as cystic changes with
      vascular wall thickening and astrocyte injury, should raise suspicion for NMOSD. 

PMID- 24029915
TI  - Living with multiple sclerosis.

PMID- 24029916
TI  - Regulation of pluripotency in male germline stem cells by Dmrt1.
AB  - Spermatogonial stem cells (SSCs) present the potential to acquire pluripotency
      under specific culture conditions. However, the frequency of pluripotent cell
      derivation is low, and the mechanism of SSC reprogramming remains unknown. In
      this study, we report that induction of global DNA hypomethylation in germline
      stem (GS) cells (cultured SSCs) induces pluripotent cell derivation. When DNA
      demethylation was triggered by Dnmt1 depletion, GS cells underwent apoptosis.
      However, GS cells were converted into embryonic stem (ES)-like cells by double
      knockdown of Dnmt1 and p53. This treatment down-regulated Dmrt1, a gene involved
      in sexual differentiation, meiosis, and pluripotency. Dmrt1 depletion caused
      apoptosis of GS cells, but a combination of Dmrt1 and p53 depletion also induced
      pluripotency. Functional screening of putative Dmrt1 target genes revealed that
      Dmrt1 depletion up-regulates Sox2. Sox2 transfection up-regulated Oct4 and
      produced pluripotent cells. This conversion was enhanced by Oct1 depletion,
      suggesting that the balance of Oct proteins maintains SSC identity. These results
      suggest that spontaneous SSC reprogramming is caused by unstable DNA methylation
      and that a Dmrt1-Sox2 cascade is critical for regulating pluripotency in SSCs. 

PMID- 24029917
TI  - Checkpoint kinases and the INO80 nucleosome remodeling complex enhance global
      chromatin mobility in response to DNA damage.
AB  - Double-strand break repair by recombination requires a homology search. In yeast,
      induced breaks move significantly more than undamaged loci. To examine whether
      DNA damage provokes an increase in chromatin mobility generally, we tracked
      undamaged loci under DNA-damaging conditions. We found that the yeast checkpoint
      factors Mec1, Rad9, and Rad53 are required for genome-wide increases in chromatin
      mobility, but not the repair protein Rad51. Mec1 activation by targeted Ddc1/Ddc2
      enhances chromatin mobility even in the absence of damage. Finally, the INO80
      chromatin remodeler is shown to act downstream from Mec1 to increase chromatin
      mobility, highlighting an additional damage-related role of this nucleosome
      remodeling complex.

PMID- 24029919
TI  - A single molecule that acts as a fluorescence sensor for zinc and cadmium and a
      colorimetric sensor for cobalt.
AB  - A new metal ion sensor that contains quinoline and pyridylaminophenol has been
      synthesized. In acetonitrile and in the presence of Zn(2+), the sensor
      fluoresces. In contrast, in aqueous solutions the sensor fluoresces in the
      presence of Cd(2+). The fluorescence of the molecule is selective for Zn(2+) or
      Cd(2+) and shows no fluorescence with other metal ions. The crystal structure of
      the Cd(2+) complex shows coordination through the amide and phenol oxygens, as
      well as the amine nitrogen of the sensor. The sensor also acts as a colorimetric
      sensor for Co(2+) by changing color from colorless to yellow. The color change is
      selective for Co(2+) and is not observed with other metal ions. The unique
      combination of pyridine and phenol groups with quinoline results in the
      properties of this sensor. 

PMID- 24029918
TI  - Inflammation-mediated skin tumorigenesis induced by epidermal c-Fos.
AB  - Skin squamous cell carcinomas (SCCs) are the second most prevalent skin cancers.
      Chronic skin inflammation has been associated with the development of SCCs, but
      the contribution of skin inflammation to SCC development remains largely unknown.
      In this study, we demonstrate that inducible expression of c-fos in the epidermis
      of adult mice is sufficient to promote inflammation-mediated epidermal
      hyperplasia, leading to the development of preneoplastic lesions. Interestingly,
      c-Fos transcriptionally controls mmp10 and s100a7a15 expression in keratinocytes,
      subsequently leading to CD4 T-cell recruitment to the skin, thereby promoting
      epidermal hyperplasia that is likely induced by CD4 T-cell-derived IL-22.
      Combining inducible c-fos expression in the epidermis with a single dose of the
      carcinogen 7,12-dimethylbenz(a)anthracene (DMBA) leads to the development of
      highly invasive SCCs, which are prevented by using the anti-inflammatory drug
      sulindac. Moreover, human SCCs display a correlation between c-FOS expression and
      elevated levels of MMP10 and S100A15 proteins as well as CD4 T-cell infiltration.
      Our studies demonstrate a bidirectional cross-talk between premalignant
      keratinocytes and infiltrating CD4 T cells in SCC development. Therefore,
      targeting inflammation along with the newly identified targets, such as MMP10 and
      S100A15, represents promising therapeutic strategies to treat SCCs. 

PMID- 24029920
TI  - Vascular access care and treatment practices associated with outcomes of
      arteriovenous fistula: international comparisons from the Dialysis Outcomes and
      Practice Patterns Study.
AB  - BACKGROUND: Vascular access (VA) guidelines recommend the native arteriovenous
      fistula (AVF) as VA of first choice for chronic hemodialysis patients. AVF
      management is important in hemodialysis patient care. AVF survival is associated
      with various physical factors, but the effects of dialysis treatment factors upon
      AVF survival are still not clear. METHODS: Study patients were treated at 498
      dialysis facilities participating in the Dialysis Outcomes and Practice Patterns
      Study (DOPPS) 2 or 3 (2002-2007). Analyses included 1,183 incident hemodialysis
      patients (on dialysis <=7 days and using an AVF at study entry) and 949 prevalent
      patients (on dialysis >7 days at DOPPS entry and using a new AVF created during
      study observation). AVF survival was modeled from the study entry date for
      incident patients and date of first AVF use for prevalent patients. Predictors of
      primary and final AVF survival were compared across Japan, North America and
      Europe/Australia/New Zealand (EUR/ANZ) with adjustments for patient
      characteristics. RESULTS: No meaningful relationship was seen between AVF
      survival and various physician and staff practices. However, patients with prior
      catheter use displayed higher rates of primary and final AVF failure. Final AVF
      failure rates were higher in facilities with higher median blood flow rates
      (BFR). They were also greater in North America and EUR/ANZ than in Japan, but
      this difference was substantially attenuated after accounting for regional
      differences in facility median BFR. CONCLUSION: AVF longevity differed according
      to the DOPPS region, and was related to prior patient catheter use and facility
      BFR practice. Further longitudinal studies may help demonstrate meaningful
      associations between VA-handling skill and patency.

PMID- 24029921
TI  - Synthesis of ultrathin CdS nanosheets as efficient visible-light-driven water
      splitting photocatalysts for hydrogen evolution.
AB  - Ultrathin CdS nanosheets with a thickness of ~4 nm have been synthesized through
      an ultrasonic-induced aqueous exfoliation method involving lamellar CdS-DETA
      hybrid nanosheets as starting materials and L-cysteine as a stabilizing agent.
      The as-obtained CdS ultrathin nanosheets exhibit efficient photocatalytic
      activity and good stability for hydrogen production.

PMID- 24029922
TI  - Evidence of two distinct local structures of water from ambient to supercooled
      conditions.
AB  - The liquid and supercooled states of water show a series of anomalies whose
      nature is debated. A key role is attributed to the formation of structural
      aggregates induced by critical phenomena occurring deep in the supercooled
      region; the nature of the water anomalies and of the hidden critical processes
      remains elusive. Here we report a time-resolved optical Kerr effect investigation
      of the vibrational dynamics and relaxation processes in supercooled bulk water.
      The experiment measures the water intermolecular vibrations and the structural
      relaxation process in an extended temperature range, and with unprecedented data
      quality. A mode-coupling analysis of the experimental data enables to
      characterize the intermolecular vibrational modes and their interplay with the
      structural relaxation process. The results bring evidence of the coexistence of
      two local configurations, which are interpreted as high-density and low-density
      water forms, with an increasing weight of the latter at low temperatures. 

PMID- 24029923
TI  - Biometric health screening for employers: consensus statement of the health
      enhancement research organization, American College of Occupational and
      Environmental Medicine, and care continuum alliance.
AB  - Employer wellness programs have grown rapidly in recent years with the interest
      in making an impact on employees' health. Successful programs are delivered
      through comprehensive solutions that are linked to an organization's business
      strategy and championed by senior leadership. Successful employee health
      management programs vary in the services, yet typically include the core
      components of health risk identification tools, behavior modification programs,
      educational programs, as well as changes to the workplace environment and
      culture. This article focuses on biometric screenings and was intended to provide
      employers and other stakeholders with information and guidance to help implement
      a successful screening program as part of an overall employee health management
      approach. The article is organized into four sections: goals and key success
      factors; methods and oversight; operations and delivery; and engagement and
      evaluation. 

PMID- 24029924
TI  - A facile approach to multicolored electrochromic triarylamine-based thermoset
      epoxy materials with tunable intervalence charge transfer behavior.
AB  - By a facile curing reaction, novel electrochromic triarylamine-based
      thermosetting epoxy materials could be readily prepared for the first time. The
      resulting multielectrochromic epoxy materials exhibited good electrochemical
      stability and large optical changes in transmittance between their bleached and
      colored states with tunable intervalence charge transfer behavior. 

PMID- 24029926
TI  - Pillar substitution modulates CO2 affinity in "mmo" topology networks.
AB  - The use of WO4(2-) instead of CrO4(2-) or MoO4(2-) as an angular pillar in
      topology nets has afforded two isostructural porous nets of formula [M(bpe)2WO4]
      (M = Co or Ni, bpe = 1,2-(4-pyridyl)ethene). The Ni variant, WOFOUR-1-Ni, is
      highly selective towards CO2 thanks to its exceptionally high isosteric heat of
      adsorption (Qst) of -65.5 kJ mol(-1) at zero loading.

PMID- 24029925
TI  - Properties that influence the specific surface areas of carbon nanotubes and
      nanofibers.
AB  - Commercially available carbon nanotubes and nanofibers were analyzed to examine
      possible relationships between their Brunauer-Emmett-Teller specific surface
      areas (SSAs) and their physical and chemical properties. Properties found to
      influence surface area were number of walls/diameter, impurities, and surface
      functionalization with hydroxyl and carboxyl groups. Characterization by electron
      microscopy, energy-dispersive X-ray spectrometry, thermogravimetric analysis, and
      elemental analysis indicates that SSA can provide insight on carbon nanomaterials
      properties, which can differ vastly depending on synthesis parameters and post
      production treatments. In this study, how different properties may influence
      surface area is discussed. The materials examined have a wide range of surface
      areas. The measured surface areas differed from product specifications, to
      varying degrees, and between similar products. Findings emphasize the multiple
      factors that influence surface area and mark its utility in carbon nanomaterial
      characterization, a prerequisite to understanding their potential applications
      and toxicities. Implications for occupational monitoring are discussed.

PMID- 24029927
TI  - An in vivo model system for evaluation of the host response to biomaterials.
AB  - We describe an in vivo model system designed to evaluate the host response to
      implanted biomaterials: The partial thickness rat abdominal wall defect model.
      The model allows for determination of the temporal and spatial distribution of
      the cellular and vascular response, the remodeling of the implanted material and
      surrounding host soft tissue, and the function of the remodeled tissue over time.

PMID- 24029928
TI  - Urothelial cell culture.
AB  - This chapter reviews the use of urothelial cells as a means to enhance tissue
      regeneration and wound healing in urinary tract system. It addresses the
      properties of urothelial cells, including their role as a permeability barrier to
      protect underlying muscle tissue from the caustic effects of urine and as one of
      the main cell types, along with smooth muscle cells, that are used in urethral or
      bladder tissue engineering today. This description includes a general overview of
      various isolation techniques and culture methods that have been developed to
      improve urinary tract reconstruction in vivo and aid the characterization of
      growth factor expression in vitro. The chapter then describes various
      applications using urothelial cells, including production of multilayer
      urothelial sheets, tissue engineered bladder mucosa, tissue engineered urethra,
      and tissue engineered bladder. It also outlines the advantages of sandwich and
      layered coculture of these cells and the effects of epithelial-stromal cell
      interactions during tissue regeneration or wound healing processes in the urinary
      tract. 

PMID- 24029929
TI  - Cell-populated collagen lattice contraction model for the investigation of
      fibroblast collagen interactions.
AB  - The fibroblast-populated collagen lattice (FPCL) was intended to act as the
      dermal component for "skin-equivalent" or artificial skin developed for skin
      grafting burn patients. The "skin-equivalent" was clinically unsuccessful as a
      skin graft, but today it is successfully used as a dressing for the management of
      chronic wounds. The FPCL has, however, become an instrument for investigating
      cell-connective tissue interactions within a three-dimensional matrix. Through
      the capacity of cell compaction of collagen fibrils, the FPCL undergoes a
      reduction in volume referred to as lattice contraction. Lattice contraction
      proceeds by cell-generated forces that reduce the water mass between collagen
      fibers, generating a closer relationship between collagen fibers. The compaction
      of collagen fibers is responsible for the reduction in the FPCL volume. Cell
      generated forces through the linkage of collagen fibers with fibroblast's
      cytoskeletal actin-rich microfilament structures are responsible for the
      completion of the collagen matrix compaction. The type of culture dish used to
      cast FPCL as well as the cell number will dictate the mechanism for compacting
      collagen matrices. Fibroblasts, at moderate density, cast as an FPCL within a
      petri dish and released from the surface of the dish soon after casting compact
      collagen fibers through cell tractional forces. Fibroblasts at moderate density
      cast as an FPCL within a tissue culture dish and not released for 4 days upon
      release show rapid lattice contraction through a mechanism of cell contraction
      forces. Fibroblasts at high density cast in an FPCL within a petri dish, released
      from the surface of the dish soon after casting, compact a collagen lattice very
      rapidly through forces related to cell elongation. The advantage of the FPCL
      contraction model is the study of cells in the three-dimensional environment,
      which is similar to the environment from which these cells were isolated. In this
      chapter methods are described for manufacturing collagen lattices, which assess
      the three forces involved in compacting and/or organizing collagen fibrils into
      thicker collagen fibers. The clinical relevance of the FPCL contraction model is
      related to advancing our understanding of wound contraction and scar contracture.

PMID- 24029930
TI  - A tissue-engineered corneal wound healing model for the characterization of
      reepithelialization.
AB  - Progress in tissue engineering has led to the discovery of technologies allowing
      reconstruction of autologous tissues from the patient's own cells and the
      development of new in vitro models to study cellular and molecular mechanisms
      implicated in wound healing. The outer surface of the eye, the cornea, is
      involved in the sense of sight, thus an adequate reepithelialization process
      after wounding is essential in order to maintain corneal function. In this
      chapter, protocols to generate a new in vitro three-dimensional human corneal
      wound healing model suitable for studying the different components that play
      important roles in corneal reepithelialization are described in details. The
      methods include extraction and culture of human corneal epithelial cells (HCECs),
      human corneal fibroblasts, a complete description of the cornea reconstructed by
      tissue-engineering as well as the corneal wound healing model. 

PMID- 24029931
TI  - Adult stem cells in small animal wound healing models.
AB  - This chapter broadly reviews the use of stem cells as a means to accelerate wound
      healing, focusing first on the properties of stem cells that make them attractive
      agents to influence repair, both alone and as vehicles for growth factor
      delivery. Major stem cell reservoirs are described, including adult, embryonic,
      and induced pluripotent cell sources, outlining the advantages and limitations of
      each source as wound healing agents, as well as the possible mechanisms
      responsible for wound healing acceleration. Finally, the chapter includes a
      materials and methods section that provides an in-depth description of adult
      tissue harvest techniques. 

PMID- 24029932
TI  - Novel animal models for tracking the fate and contributions of bone marrow
      derived cells in diabetic healing.
AB  - There is a vast wealth of information to be gained by tracking both the fate and
      contribution of individual cell types to the wound healing response. This is
      particularly important in research focused on impaired healing, such as diabetic
      wound healing, where the number or function of one or more specific cell types
      may be abnormal and contribute to the observed healing derangements.
      Specifically, diabetic wounds have been shown to have an overactive inflammatory
      response and decreased angiogenesis. The ability to track specific cell types
      participating in these responses would dramatically improve our understanding of
      the cellular derangements in diabetic healing. In this chapter, we review two
      novel chimeric models based on the leptin deficient Db/Db mouse. The use of these
      models allows for the tracking of bone marrow derived inflammatory and progenitor
      cell populations as well as the determination of the molecular contributions of
      these cell populations to the wound healing response. 

PMID- 24029933
TI  - Neural repair with pluripotent stem cells.
AB  - The nervous system is characterized by its complex network of highly specialized
      cells that enable us to perceive stimuli from the outside world and react
      accordingly. The computational integration enabled by these networks remains to
      be elucidated, but appropriate sensory input, processing, and motor control are
      certainly essential for survival. Consequently, loss of nervous tissue due to
      injury or disease represents a considerable biomedical challenge. Stem cell
      research offers the promise to provide cells for nervous system repair to replace
      lost and damaged neural tissue and alleviate disease. We provide a protocol-based
      chapter on fundamental principles and procedures of pluripotent stem cell (PSC)
      differentiation and neural transplantation. Rather than detailed methodological
      step-by-step descriptions of these procedures, we provide an overview and
      highlight the most critical aspects and key steps of PSC neural induction,
      subtype specification in different in vitro systems, as well as neural cell
      transplantation to the central nervous system. We conclude with a summary of
      suitable readout methods including in vitro phenotypic analysis, histology, and
      functional analysis in vivo.

PMID- 24029934
TI  - Cell-based therapies for myocardial repair: emerging role for bone marrow-derived
      mesenchymal stem cells (MSCs) in the treatment of the chronically injured heart.
AB  - Accumulating data support the use of bone marrow (BM)-derived MSCs in animal
      models (e.g., swine) to restore cardiac function and tissue perfusion in chronic
      cardiac injury. Based on results obtained in swine, we are currently conducting
      phase I/II clinical trials to address the safety, cell type, cell dose, delivery
      technique, and efficacy of MSCs in patients with chronic heart failure. MSCs for
      these trials are isolated from harvested BM and then processed and expanded for
      intracardiac injection. The BM-MSCs in use for the clinical trials are of
      clinical grade having been processed successfully in an FDA-approved cGMP
      facility. 

PMID- 24029935
TI  - A model system for primary abdominal closures.
AB  - The foreign body response to medical devices and materials implanted in the human
      body, including scarring, fibrous encapsulation, and potential rejection, is a
      longstanding and serious clinical issue. There are no widely acceptable or safe
      therapies for ameliorating the foreign body response. Clinical complications
      resulting from the response include disfigurement of silicone prostheses and loss
      of function of devices such as implanted pacemakers, stents, and shunts.
      Cellularized implants and stem cells placed in the body are also subject to the
      foreign body response with the added issue that the regenerative repair intended
      to be prompted by the graft may be inhibited. Beneficial modification of the
      body's reaction to implanted materials, medical devices, engineered constructs,
      or stem cells would be a fundamentally important therapeutic advance.As part of
      investigating the cellular response, we have developed a model which uses cells
      isolated from skeletal muscle biopsy, cultured, and proliferated in vitro. These
      satellite cells, which are mononucleated progenitor cells, reside between the
      plasma membrane of the muscle fiber and the basal membrane that encompasses the
      fiber. While usually quiescent, these cells become activated following muscle
      damage. Once activated, the satellite cells proliferate, migrate to injured
      muscle, and participate in repair by fusing with existing muscle fibers or by
      differentiating into new skeletal muscle fibers. Satellite cells have been shown
      to be heterogeneous populations of stem cells and progenitor cells. We have
      developed an explant method for isolating, sorting, enriching, and culturing
      these cells for use in skeletal muscle regenerative medicine to determine if the
      foreign body response can be inhibited by manipulating the cell-cell
      communication.

PMID- 24029936
TI  - Alternatives for animal wound model systems.
AB  - In this chapter a review of animal model systems already being utilized to study
      normal and pathologic wound healing is provided. We also go into details on
      alternatives for animal wound model systems. The case is made for limitations in
      the various approaches. We also discuss the benefits/limitations of in vitro/ex
      vivo systems bringing everything up to date with our current work on developing a
      cell-based reporter system for diabetic wound healing. 

PMID- 24029937
TI  - Novel methods for the investigation of human hypertrophic scarring and other
      dermal fibrosis.
AB  - Hypertrophic scar (HTS) represents the dermal equivalent of fibroproliferative
      disorders that occur after injury involving the deep dermis while superficial
      wounds to the skin heal with minimal or no scarring. HTS is characterized by
      progressive deposition of collagen that occurs with high frequency in adult
      dermal wounds following traumatic or thermal injury. Increased levels of
      transforming growth factor-beta1 (TGF-beta1), decreased expression of small
      leucine-rich proteoglycans (SLRPs), and/or fibroblast subtypes may influence the
      development of HTS. The development of HTS is strongly influenced by the cellular
      and molecular properties of fibroblast subtypes, where cytokines such as fibrotic
      TGF-beta1 and CTGF as well as the expression of SLRPs, particularly decorin and
      fibromodulin, regulate collagen fibrillogenesis and the activity of TGF-beta1.
      Reduced anti-fibrotic molecules in the ECM of the deep dermis and the distinctive
      behavior of the fibroblasts in this region of the dermis which display increased
      sensitivity to TGF-beta1's biological activity contribute to the development of
      HTS following injury to the deep dermis. By comparing the cellular and molecular
      differences involved in deep and superficial wound healing in an experimental
      wound scratch model in humans that has both superficial and deep injuries within
      the same excisional model, our aim is to increase our understanding of how tissue
      repair following injury to the deep dermis can be changed to promote healing with
      a similar pattern to healing that occurs following superficial injury that
      results in no or minimal scarring. Studying the characteristics of superficial
      dermal injuries that heal with minimal scarring will help us identify therapeutic
      approaches for tissue engineering and wound healing. In addition, our ability to
      develop novel therapies for HTS is hampered by limitations in the available
      animal models used to study this disorder in vivo. We also describe a nude mouse
      model of transplanted human skin that develops a hypertrophic proliferative scar
      consistent morphologically and histologically with human HTS, which can be used
      to test novel treatment options for these dermal fibrotic conditions. 

PMID- 24029938
TI  - Study of the human chronic wound tissue: addressing logistic barriers and
      productive use of laser capture microdissection.
AB  - Direct procurement of tissue samples from clinically presented chronic human
      wounds is a powerful approach to understand mechanism at play in an actual
      problem wound. While such approach suffers from limitations related to lack of
      reproducible conditions across wounds, something that we are used to in the
      laboratory while studying wounds on experimental animals, the direct study of
      human wound tissue helps recognize the right questions to ask in the laboratory.
      Going back and forth between human wound and experimental animal studies helps
      steer studies on experimental wounds in a clinically relevant direction. In this
      chapter, we describe critical factors that need to be considered prior to
      planning a study involving human wound samples. In addition, we describe an
      approach to capture wound hyperproliferative epithelium (HE) from chronic human
      wound biopsies using laser capture microdissection (LCM). LCM is a new technology
      applicable to a broad range of clinical research and represents a catalyst of
      sophisticated translational research. 

PMID- 24029939
TI  - The wound watch: an objective staging system for wounds in the diabetic (db/db)
      mouse model.
AB  - As in cancer biology, in wound healing there is a need for objective staging
      systems to decide for the best treatment and predictors of outcome. We developed
      in the diabetic (db/db) wound healing model, a staging system, the "wound watch,"
      based on the quantification of angiogenesis and cell proliferation in open
      wounds. In chronic wounds, there is often a lack of cellular proliferation and
      angiogenesis that leads to impaired healing. The wound watch addresses this by
      quantifying the proliferative phase of wound healing in two dimensions (cellular
      division and angiogenesis). The results are plotted in a two-dimensional graph to
      monitor the course of healing and compare the response to different treatments. 

PMID- 24029940
TI  - Human ex vivo wound healing model.
AB  - Wound healing is a spatially and temporally regulated process that progresses
      through sequential, yet overlapping phases and aims to restore barrier breach. To
      study this complex process scientists use various in vivo and in vitro models.
      Here we provide step-by-step instructions on how to perform and employ an ex vivo
      wound healing model to assess epithelization during wound healing in human skin. 

PMID- 24029941
TI  - Murine models of human wound healing.
AB  - In vivo wound healing experiments remain the most predictive models for studying
      human wound healing, allowing an accurate representation of the complete wound
      healing environment including various cell types, environmental cues, and
      paracrine interactions. Small animals are economical, easy to maintain, and allow
      researchers to take advantage of the numerous transgenic strains that have been
      developed to investigate the specific mechanisms involved in wound healing and
      regeneration. Here we describe three reproducible murine wound healing models
      that recapitulate the human wound healing process. 

PMID- 24029942
TI  - A corneal scarring model.
AB  - Corneal opacification (i.e., haze) following a non-denaturing acute injury to the
      cornea is a process which takes about 5 days to manifest itself, indicating that
      it is the consequence of cellular and molecular biological processes. In order to
      obtain a better understanding of the haze development process, and to test
      candidate anti-haze therapies, we use a corneal scarring model whereby we create
      an excimer laser wound in the center of rabbit corneas. The primary data
      generated by this model are (1) changes in corneal thickness with time; (2) wound
      closure rates, or re-epithelialization; (3) changes in the location and density
      of corneal sub-epithelial haze; and (4) molecular and histological changes
      leading up to, during, and following the formation of haze. While the use of
      excimer lasers to generate consistent wounds in rabbit corneas is not a novel
      protocol for the study of corneal haze, the photographic technique presented here
      for the more objective recording and quantification of corneal haze is. At
      present, a qualitative, semiquantitative, grading system is employed whereby the
      amount of iris detail discernible through the scar is assigned a value between 0
      and 4. Such a system makes direct comparisons amongst reported anti-haze trials
      nearly impossible. Furthermore, the additional "geographic" detail provided by
      the image provides a new layer of information about the formation of haze and the
      ability to troubleshoot dosing regimens. Altogether, with the information present
      herein, we believe that the study of corneal haze formation and the ability to
      compare and contrast candidate therapies are both greatly improved.

PMID- 24029943
TI  - A novel and efficient model of coronary artery ligation in the mouse.
AB  - Coronary artery ligation to induce myocardial infarction (MI) and
      ischemia/reperfusion (I/R) injury in mice is typically performed by an invasive
      and time-consuming approach that requires ventilation and a full thoracotomy
      (classical method), often resulting in extensive tissue damage and high
      mortality. Here, we describe a novel and rapid surgical method to induce MI that
      does not require ventilation. This method is much more efficient and safer than
      the classical method of MI and I/R injury. 

PMID- 24029945
TI  - Injury models to study cardiac remodeling in the mouse: myocardial infarction and
      ischemia-reperfusion.
AB  - Deep tissue wound healing requires a complex sequence of several factors working
      in unison to repair the organ at risk. Myocardial infarction (MI) is particularly
      complex due to several local and systemic factors mediating the repair process
      within the heart. The wound healing process during this time is critical-the
      cardiac myocytes are at risk of apoptotic cell death, autophagy, and necrosis.
      During the early remodeling period, the fibroblasts and myofibroblasts play
      critical roles in infarct scar formation, a process that is greatly influenced by
      a robust inflammatory response. Construction of the infarct scar is a "necessary
      evil" that helps to limit expansion of the infarction; however, the collagen and
      matrix deposition will often spread to the healthy areas of the heart, causing
      reactive fibrosis in areas remote from the original damage. This chapter outlines
      in detail the procedures for two myocardial infarction injury models as well as
      how to quantify the size of the experimentally induced injury. These procedures
      are critical to the development of in vivo approaches to study myocardial injury,
      particularly for use in knockout and transgenic mice. 

PMID- 24029944
TI  - Cardiac wound healing post-myocardial infarction: a novel method to target
      extracellular matrix remodeling in the left ventricle.
AB  - Myocardial infarction (MI) is a leading cause of death worldwide. Permanent
      ligation of the left anterior descending coronary artery (LAD) is a commonly used
      surgical model to study post-MI effects in mice. LAD occlusion induces a robust
      wound healing response that includes extracellular matrix (ECM) remodeling. This
      chapter provides a detailed guide on the surgical procedure to permanently ligate
      the LAD. Additionally, we describe a prototype method to enrich cardiac tissue
      for ECM, which allows one to focus on ECM remodeling in the left ventricle
      following surgically induced MI in mice. 

PMID- 24029946
TI  - Cryoinjury models of the adult and neonatal mouse heart for studies of scarring
      and regeneration.
AB  - A major limitation in studies of the injured heart is animal-to-animal
      variability in wound size resulting from commonly used techniques such as left
      anterior descending coronary artery ligation. This variability can make standard
      errors sufficiently large that mean separation between treatment and control
      groups can be difficult without replicating numbers (n) of animals in groups by
      excessive amounts. Here, we describe the materials and protocol necessary for
      delivering a standardized non-transmural cryoinjury to the left ventricle of an
      adult mouse heart that may in part obviate the issue of injury variance between
      animals. As reported previously, this cryoinjury model generates a necrotic wound
      to the ventricle of consistent size and shape that resolves into a scar of
      uniform size, shape, and organization. The cryo-model also provides an extended
      injury border zone that exhibits classic markers of remodeling found in surviving
      cardiac tissue at the edge of a myocardial infarction, including connexin43
      (Cx43) lateralization. In a further extension of the method, we describe how we
      have adapted the model to deliver a cryoinjury to the apex of the heart of
      neonatal mice-a modification that may be useful for studies of myocardial
      regeneration in mammals. 

PMID- 24029947
TI  - Targeting Wnt signaling to improve wound healing after myocardial infarction.
AB  - Myocardial infarction is one of the major causes of left ventricular dilatation,
      frequently leading to heart failure. In the last decade, the wound healing
      process that takes place in the infarct area after infarction has been recognized
      as a novel therapeutic target to attenuate left ventricular dilatation and
      preserve an adequate cardiac function. In this chapter, we discuss the role of
      Wnt signaling in the wound healing process after infarction, with a specific
      focus on its modulating effect on myofibroblast characteristics. 

PMID- 24029948
TI  - Vascular connexins in restenosis after balloon injury.
AB  - Atherosclerosis is an arterial progressive disease characterized by accumulation
      of lipids, macrophages, T lymphocytes, and smooth muscle cells in large- and
      medium-sized arteries. Erosion and rupture of the atherosclerotic plaque may
      induce myocardial infarction and cerebrovascular accidents that are responsible
      for a large percentage of sudden death. Atherosclerosis is often treated by
      angioplasty generally followed by stent implantation. Although angioplasty and
      stent implantation are necessary for the survival of the patient, they induce a
      trauma in the vessel wall that favors a vascular reaction called restenosis and
      the associated de-endothelialization increases the risk of thrombosis. To study
      mechanisms involved in restenosis and thrombus formation, animal models have been
      developed. In this chapter, we describe the experimental model of balloon injury
      adapted for mice and apply it to study the role of Cx43 in this process.
      Connexins are members of a large family of transmembrane proteins that allow
      exchange of ions and small metabolites between cytosol and extracellular space or
      between neighboring cells. Connexins are important in vascular physiology, they
      support radial and longitudinal cell-to-cell communication in the vascular wall,
      and have been shown to modulate vascular pathologies such as atherosclerosis and
      hypertension. We also describe the various connexin-specific tools, for example,
      transgenic mice, blocking peptides, antisense, and siRNA, and their value in
      obtaining insight into the role of Cx43 in restenosis and thrombus formation
      after vascular injury. 

PMID- 24029949
TI  - Gain-of-function assays in the axolotl (Ambystoma mexicanum) to identify
      signaling pathways that induce and regulate limb regeneration.
AB  - The adult salamander has been studied as a model for regeneration of complex
      tissues for many decades. Only recently with the development of gain-of-function
      assays for regeneration, has it been possible to screen for and assay the
      function of the multitude of signaling factors that have been identified in
      studies of embryonic development and tumorigenesis. Given the conservation of
      function of these regulatory pathways controlling growth and pattern formation,
      it is now possible to use the functional assays in the salamander to test the
      ability of endogenous as well as small-molecule signaling factors to induce a
      regenerative response. 

PMID- 24029950
TI  - The mouse digit tip: from wound healing to regeneration.
AB  - A challenge to the study of regeneration is determining at what point the
      processes of wound healing and regeneration diverge. The mouse displays level
      specific regeneration responses. An amputation through the distal third of the
      terminal phalanx will prompt a regeneration response and result in a new digit
      tip that mimics the morphology of the lost digit tip. Conversely, an amputation
      through the distal third of the intermediate phalanx initiates a wound healing
      and scarring response. The mouse, therefore, provides a model for studying the
      transition between wound healing and regeneration in the same animal. This
      chapter details the methods used in the study of mammalian digit regeneration,
      including a method to introduce exogenous protein into the mouse digit amputation
      model via microcarrier beads and methods for analysis of bone regeneration. 

PMID- 24029951
TI  - Lower vibrissa follicle amputation: a mammalian model of regeneration.
AB  - Regeneration of damaged or lost cells, tissues, and organs continues to fascinate
      and intrigue researchers with the lure of creating beneficial therapeutics for
      use in wound healing and regenerative medicine. However, unlike many other
      animals, wound healing in mammalian species typically proceeds via imperfect
      repair rather than authentic regeneration of tissues. Here, we describe a model
      of mammalian regeneration which can be used by researchers to investigate
      conditions that permit renewal of lost tissue and identify potential barriers to
      mammalian regeneration. The methods describe the surgical procedures for
      amputation of the lower third of the whisker follicle (vibrissa) in the mouse, as
      well as subsequent isolation and processing of the regenerating follicles for
      analysis. 

PMID- 24029952
TI  - Using Drosophila larvae to study epidermal wound closure and inflammation.
AB  - This methods chapter describes two methods for creating epithelial wounds in
      Drosophila larvae: pinch and puncture wounding. It also covers protocols for
      visualizing epithelial wounds, either in a dissected whole mount preparation or,
      using transgenic reporter larvae, in a live whole mount preparation. Finally,
      useful transgenic lines for live genetic screening of genes required for wound
      closure or inflammation are described. 

PMID- 24029954
TI  - Quantifying alterations in cell migration: tracking fluorescently-tagged
      migrating cells by FACs and live-imaging.
AB  - Cell migration is fundamental to many different physiological processes including
      embryonic development, inflammation and wound healing. Given the range and
      importance cell migration plays a number of assays have been developed to measure
      different aspects of cell migration. Here we describe two different methods to
      analyze cell migration. The first method analyzes the migration of fluorescently
      tagged cells using Boyden chambers and FACs and the second looks at migration
      properties using time-lapse microscopy. 

PMID- 24029953
TI  - Zebrafish cardiac injury and regeneration models: a noninvasive and invasive in
      vivo model of cardiac regeneration.
AB  - Despite current treatment regimens, heart failure still remains one of the
      leading causes of morbidity and mortality in the world due to failure to
      adequately replace lost ventricular myocardium from ischemia-induced infarct.
      Although adult mammalian ventricular cardiomyocytes have a limited capacity to
      divide, this proliferation is insufficient to overcome the significant loss of
      myocardium from ventricular injury. However, lower vertebrates, such as the
      zebrafish and newt, have the remarkable capacity to fully regenerate their hearts
      after severe injury. Thus, there is great interest in studying these animal model
      systems to discover new regenerative approaches that might be applied to injured
      mammalian hearts. To this end, the zebrafish has been utilized more recently to
      gain additional mechanistic insight into cardiac regeneration because of its
      genetic tractability. Here, we describe two cardiac injury methods, a mechanical
      and a genetic injury model, for studying cardiac regeneration in the zebrafish. 

PMID- 24029955
TI  - Examining the role of mast cells in fetal wound healing using cultured cells in
      vitro.
AB  - Mast cells play an important role during the inflammatory phase of wound healing,
      and studies suggest that they also influence scar formation and remodeling.
      Recently, our laboratory has characterized the mast cell response to injury in a
      fetal wound healing model. In this model, early gestation fetal skin regenerates
      and heals without a scar (scarless wounds) and late gestation skin heals with a
      scar (fibrotic wounds). Differences in mast cell number, maturity, and activity
      were identified between scarless and scar-forming fetal wounds. To study mast
      cell function in more detail, in vitro experiments are useful. This chapter
      outlines methods to expand, purify, and study the function of mast cells
      harvested from murine fetal skin. Using these methods, cultured mast cells retain
      many of the differences in maturity and activation seen during fetal skin
      development in vivo. Studying the function of mast cells in vitro could help
      define the mechanisms by which mast cells contribute to wound repair and
      ultimately lead to better therapies for improving wound repair and reducing scar
      formation. 

PMID- 24029956
TI  - Assessing macrophage phenotype during tissue repair.
AB  - Macrophages are thought to play important roles in tissue repair, from host
      defense to angiogenesis and new tissue formation. The role of macrophages in
      repair of different tissues is an active area of inquiry, particularly in
      settings of impaired healing. In this chapter, we describe methods for isolating
      monocyte/macrophage cell populations from damaged tissue and characterizing the
      phenotype of these cells. Cells are isolated from tissue by enzymatic digestion,
      and then monocyte/macrophage populations can be sorted by magnetic separation.
      The phenotype of these cells is assessed by real-time PCR, flow cytometry and
      ELISA. A complementary approach of assessing monocyte/macrophage phenotype by
      immunofluorescence staining of cryosections is also described. This combination
      of approaches to study the macrophage phenotypes expressed during tissue repair
      will lead to better understanding of the roles of macrophages in tissue repair
      and new therapeutic avenues for improving healing. 

PMID- 24029957
TI  - The use of connexin-based therapeutic approaches to target inflammatory diseases.
AB  - Alterations in Connexin43 (Cx43) expression levels have been shown to play a role
      in inflammatory processes including skin wounding and neuroinflammation. Cx43
      protein levels increase following a skin wound and can inhibit wound healing.
      Increased Cx43 has been observed following stroke, epilepsy, ischemia, optic
      nerve damage, and spinal cord injury with gap junctional communication and
      hemichannel opening leading to increased secondary damage via the inflammatory
      response. Connexin43 modulation has been identified as a potential target for
      protection and repair in neuroinflammation and skin wound repair. This review
      describes the use of a Cx43 specific antisense oligonucleotide (Cx43 AsODN) and
      peptide mimetics of the connexin extracellular loop domain to modulate Cx43
      expression and/or function in inflammatory disorders of the skin and central
      nervous system. An overview of the role of connexin43 in inflammatory conditions,
      how antisense and peptide have allowed us to elucidate the role of Cx43 in these
      diseases, create models of diseases to test interventions and their potential for
      use clinically or in current clinical trials is presented. Antisense
      oligonucleotides are applied topically and have been used to improve wound
      healing following skin injury. They have also been used to develop ex vivo models
      of neuroinflammatory diseases that will allow testing of intervention strategies.
      The connexin mimetic peptides have shown potential in a number of
      neuroinflammatory disorders in ex vivo models as well as in vivo when delivered
      directly to the injury site or when delivered systemically. 

PMID- 24029958
TI  - Commercialization: patenting and licensing in wound healing and regenerative
      biology.
AB  - Wound healing and regeneration is an area rich in discovery and progress. Models
      of resourcing science are changing, thus there are both research funding and
      commercial incentives for developing intellectual property. This chapter focuses
      on the initial steps of commercial development of a patentable discovery such as
      might apply to an invention in this space, and indeed other areas of biomedical
      science. We cover the basics of patent protection and licensing. First, we
      address why research results often need to be patented in order to provide an
      incentive for the financial investment required to move a product through the
      development and approval process. Second, we discuss the basics of US patent law
      and address certain pitfalls of premature disclosure of research results. Next,
      we inform the reader of significant issues relative to ownership of IP in the
      academic and industrial worlds, in particular the interplay of consulting
      agreements and employment obligations. Finally an overview of the mechanics of
      the licensing process is provided. 

PMID- 24029959
TI  - Translational strategies for the development of a wound healing technology (idea)
      from bench to bedside.
AB  - This chapter will outline strategies and ideas for the commercialization a
      promising wound healing technology discovered in an academic setting. This would
      include, but not limited to addressing topics such as intellectual property
      protection, funding, technology development, and regulatory aspects (i.e.,
      navigating through the FDA). 

PMID- 24029960
TI  - Triceps skinfold as a prognostic predictor in outpatient heart failure.
AB  - BACKGROUND: Most reports regarding the obesity paradox have focused on body mass
      index (BMI) to classify obesity and the prognostic values of other indirect
      measurements of body composition remain poorly examined in heart failure (HF).
      OBJECTIVE: To evaluate the association between BMI and other indirect, but easily
      accessible, body composition measurements associated with the risk of all-cause
      mortality in HF. METHODS: Anthropometric parameters of body composition were
      assessed in 344 outpatients with a left ventricular ejection fraction (LVEF) of
      <50% from a prospective HF cohort that was followed-up for 30 +/- 8.2 months.
      Survival was evaluated using the Kaplan-Meier method and Cox proportional hazard
      regression analysis. RESULTS: HF patients were predominantly male, of non
      ischemic etiology, and had moderate to severe LV systolic dysfunction (mean LVEF
      = 32 +/- 9%). Triceps skinfold (TSF) was the only anthropometric index that was
      associated with HF prognosis and had significantly lower values in patients who
      died (p = 0.047). A TSF > 20 mm was present in 9% of patients that died and 22%
      of those who survived (p = 0.027). Univariate analysis showed that serum
      creatinine level, LVEF, and NYHA class were associated with the risk of death,
      while Cox proportional hazard regression analysis showed that TSF > 20 was a
      strong independent predictor of all-cause mortality (hazard ratio = 0.36; 95%
      confidence interval = 0.13-0.97, p = 0.03). CONCLUSION: Although BMI is the most
      widely used anthropometric parameter in clinical practice, our results suggested
      that TSF is a better predictive marker of mortality in HF outpatients.

PMID- 24029961
TI  - Serum adiponectin and cardiometabolic risk in patients with acute coronary
      syndromes.
AB  - BACKGROUND: The adipose tissue is considered not only a storable energy source,
      but mainly an endocrine organ that secretes several cytokines. Adiponectin, a
      novel protein similar to collagen, has been found to be an adipocyte-specific
      cytokine and a promising cardiovascular risk marker. OBJECTIVES: To evaluate the
      association between serum adiponectin levels and the risk for cardiovascular
      events in patients with acute coronary syndromes (ACS), as well as the
      correlations between adiponectin and metabolic, inflammatory, and myocardial
      biomarkers. METHODS: We recruited 114 patients with ACS and a mean 1.13-year
      follow-up to measure clinical outcomes. Clinical characteristics and biomarkers
      were compared according to adiponectin quartiles. Cox proportional hazard
      regression models with Firth's penalization were applied to assess the
      independent association between adiponectin and the subsequent risk for both
      primary (composite of cardiovascular death/non-fatal acute myocardial infarction
      (AMI)/non-fatal stroke) and co-primary outcomes (composite of cardiovascular
      death/non-fatal AMI/non-fatal stroke/rehospitalization requiring
      revascularization). RESULTS: There were significant direct correlations between
      adiponectin and age, HDL-cholesterol, and B-type natriuretic peptide (BNP), and
      significant inverse correlations between adiponectin and waist circumference,
      body weight, body mass index, Homeostasis Model Assessment (HOMA) index,
      triglycerides, and insulin. Adiponectin was associated with higher risk for
      primary and co-primary outcomes (adjusted HR 1.08 and 1.07/increment of 1000; p =
      0.01 and p = 0.02, respectively). CONCLUSION: In ACS patients, serum adiponectin
      was an independent predictor of cardiovascular events. In addition to the
      anthropometric and metabolic correlations, there was a significant direct
      correlation between adiponectin and BNP.

PMID- 24029962
TI  - Does the aging process significantly modify the Mean Heart Rate?
AB  - BACKGROUND: The Mean Heart Rate (MHR) tends to decrease with age. When adjusted
      for gender and diseases, the magnitude of this effect is unclear. OBJECTIVES: To
      analyze the MHR in a stratified sample of active and functionally independent
      individuals. METHODS: A total of 1,172 patients aged > 40 years underwent Holter
      monitoring and were stratified by age group: 1 = 40-49, 2 = 50-59, 3 = 60-69, 4 =
      70-79, 5 = > 80 years. The MHR was evaluated according to age and gender,
      adjusted for Hypertension (SAH), dyslipidemia and non-insulin dependent diabetes
      mellitus (NIDDM). Several models of ANOVA, correlation and linear regression were
      employed. A two-tailed p value <0.05 was considered significant (95% CI).
      RESULTS: The MHR tended to decrease with the age range: 1 = 77.20 +/- 7.10; 2 =
      76.66 +/- 7.07; 3 = 74.02 +/- 7.46; 4 = 72.93 +/- 7.35; 5 = 73.41 +/- 7.98 (p <
      0.001). Women showed a correlation with higher MHR (p <0.001). In the ANOVA and
      regression models, age and gender were predictors (p < 0.001). However, R2 and
      ETA2 < 0.10, as well as discrete standardized beta coefficients indicated reduced
      effect. Dyslipidemia, hypertension and DM did not influence the findings.
      CONCLUSION: The MHR decreased with age. Women had higher values of MHR,
      regardless of the age group. Correlations between MHR and age or gender, albeit
      significant, showed the effect magnitude had little statistical relevance. The
      prevalence of SAH, dyslipidemia and diabetes mellitus did not influence the
      results.

PMID- 24029963
TI  - Renal sympathetic denervation for resistant hypertension treatment : current
      perspectives.
AB  - The authors review the concept of resistant hypertension and the involvement of
      the sympathetic nervous system in hypertension as a rational basis for the
      technique of renal sympathetic denervation (RSD) performed percutaneously. This
      revision is the result of an active search for scientific articles with the term
      "renal denervation" in the Medline and PubMed databases. The techniques and
      devices used in the procedure are presented, as well as clinical outcomes at six,
      12 and 24 months after the intervention with the Symplicity catheter. Significant
      decreases and progressively higher reductions of systolic and diastolic blood
      pressure were observed after RSD. The complication rate was minimal. New devices
      for RSD and its ongoing clinical studies are cited. In conclusion, the RSD
      presents itself as an effective and safe approach to resistant hypertension.
      Results from ongoing studies and longer follow-up of these patients are expected
      to confirm the initial results and put into perspective the expansion of the
      procedure use in hypertension approach.

PMID- 24029964
TI  - Microwave-assisted green synthesis of ultrasmall fluorescent water-soluble silver
      nanoclusters and its application in chiral recognition of amino acids.
AB  - In this article, we established a fluorescent chiral recognition and detection
      method for cysteine based on the L-glutathione (L-GSH)-stabilized Ag nanoclusters
      (AgNCs) with high selectivity and sensitivity. A fast and green microwave (MW)
      assisted strategy has been employed for synthesizing water-soluble fluorescent L
      GSH-AgNCs. The reaction time was shortened from hours to several minutes. The
      synthetic process utilized L-glutathione as a stabilizing agent and a reducing
      agent without any other toxic reducing agent, such as NaBH4 or N2H4. The method
      is environmental friendly. Due to the different responses to AgNCs from chiral
      cysteine, we found d-cysteine hardly affects the fluorescence intensity of the
      AgNCs, whereas L-cysteine distinctly weakened its fluorescence intensity. This
      experiment indicated that fluorescence quenching efficiency of AgNCs was
      proportional to the concentration of L-cysteine in the range from 0.025 to 50
      MUmol L(-1).

PMID- 24029965
TI  - Lilian Lindsay's crusade goes on.

PMID- 24029966
TI  - Welcome news.

PMID- 24029967
TI  - Bifid mandibular canals.

PMID- 24029968
TI  - Worrying attitudes.

PMID- 24029970
TI  - HIV rules changes 'a victory for common sense'.

PMID- 24029981
TI  - NICE or not so NICE?
AB  - This article provides an opinion on the NHS NICE guidance on wisdom tooth removal
      introduced in 2000. Guidelines should support clinical decision-making by
      providing recommendations based on sound evidence but the wisdom tooth guidelines
      were published without any research evidence. General dentists and oral surgeons
      in England and Wales are under pressure to comply with this guidance but what
      have been the implications for patient care? There is growing evidence that
      patients have not been best served, with significant numbers developing caries in
      an adjacent tooth before consideration of wisdom tooth assessment. 

PMID- 24029983
TI  - Oral surgery: part 1. Introduction and the management of the medically
      compromised patient.
AB  - This paper is intended to provide an overview of current thinking in the more
      relevant medical conditions to oral surgery for primary care practitioners,
      giving the detail necessary to assist the primary dental clinical team in caring
      for patients with oral complaints that may be seen in general dental practice.
      Space precludes inclusion of discussion and illustration of uncommon or more
      complex medical conditions. Clinical tips for planning, execution and post
      surgical care are discussed, and a brief overview of pre-operative, peri- and
      post-operative care is provided to minimise risk. 

PMID- 24029989
TI  - Summary of: recruitment and participation in pre-school and school-based fluoride
      varnish pilots - the South Central experience.
AB  - OBJECTIVE: To assess recruitment and participation within seven school/pre-school
      based programmes for fluoride varnish applications. METHOD: Year-long pilots were
      undertaken in six primary schools (ages four to five years) and one pre-school
      (aged three years). Three applications of fluoride varnish were carried out
      coinciding with the three school terms. RESULTS: In spite of intensive
      recruitment efforts, only 78% of the total 589 children were enrolled in the
      pilot; 15% had to be excluded because no response could be obtained from their
      parents. At the end of 12 months, 79% of enrolled children (62% of total) had
      received all three applications. Children did not receive applications because
      they were absent on the days when the dental team were carrying out the screening
      or fluoride varnish applications, were ill, or because the child refused. The
      highest refusal rate was in the pre-school. CONCLUSIONS: Younger children need to
      be targeted if improvement in the oral health of five-year-olds is to be
      achieved, the only dental measure in the Public Health Outcomes Framework, but
      they were less likely to cooperate. More research is needed on approaches to
      maximise participation in community programmes such as this, if they are to
      achieve significant population-level improvements in child dental health.

PMID- 24029990
TI  - An investigation of complete denture teaching in the UK: part 2. The DF1
      experience.
AB  - AIM: This paper, the second in a series of two (see 2013; 215: 177-181),
      investigates the opinions of a cohort of dental foundation year 1 (DF1)
      practitioners regarding their skills and competence in relation to their
      educational background in complete dentures. MATERIALS AND METHODS: With the
      permission of the Dean of the London Deanery a questionnaire was emailed to the
      ten London Foundation year 1 training schemes for distribution to approximately
      100 DF1s. Five schemes responded with total of 56 completed questionnaires (56%).
      RESULTS: The average number of complete dentures made as undergraduates was
      three. Forty-six percent had no experience in making copy dentures. An average of
      2 (median 2.05) immediate replacement dentures were made; only 10% made 8-15
      dentures. None had experience in implant-supported dentures. Thirty-five percent
      enjoyed their undergraduate training whereas 45% did not. Thirty-seven percent
      felt that their training had given them experience and confidence in complete
      dentures but 32% were of the opposite opinion. Sixty-three percent felt complete
      dentures were an important or very important aspect of dentistry. Six percent
      completely disagreed. The majority were confident in making impressions while 39%
      lacked confidence in registering jaw relations. Thirty-five percent were
      confident with chairside adjustments at the intermediary treatment stages but 28%
      were not. Sixty-three percent were confident in the fitting of new dentures and
      64% with the after-care. There was no significant gender difference in the
      responses. There was a significant difference between the London and non-London
      trained DF1s. The London trained respondents made significantly fewer dentures
      than the non-London trained cohort. The latter also rated complete denture
      treatment as being more important. The comments section revealed that 43% felt
      that they had a lack of experience; only 5% were confident, 16% thought that
      complete denture treatment would become obsolete and only 5% recognised the
      continuing importance of complete denture treatment. CONCLUSION: There is a
      disparity between the comments which indicate a lack of confidence in complete
      denture treatment and the response to the questionnaire. Other authors have
      commented on the lack of experience that has resulted in new graduates entering
      vocational training with little confidence in complete denture techniques. This
      report has highlighted these difficulties with respect to a current cohort of
      DF1s.

PMID- 24029991
TI  - How do we improve quality in primary dental care?
AB  - Quality improvement differs from quality assurance (which is retrospective in
      nature) in that it attempts to use a quality assessment cycle and focuses on the
      organisation or system of production as a whole. In this paper, the third in a
      series of three published in this Journal, we discuss the concept and evidence
      base of quality improvement, the main approaches that have been used in other
      healthcare settings and the importance of a multi-faceted strategy to address
      this issue. These topics are then related to the context of primary dental care
      and the way dentistry currently addresses quality improvement. Finally, we set
      out an agenda and provide recommendations for a system-based quality improvement
      strategy for primary dental care and identify the likely barriers and
      facilitators for this approach. 

PMID- 24030007
TI  - Commemorative plaques.

PMID- 24030010
TI  - Recruitment and participation in pre-school and school-based fluoride varnish
      pilots - the South Central experience.
AB  - OBJECTIVE: To assess recruitment and participation within seven school/pre-school
      based programmes for fluoride varnish applications. METHOD: Year-long pilots were
      undertaken in six primary schools (ages four to seven years) and one pre-school
      (ages three to four years). Three applications of fluoride varnish were carried
      out coinciding with the three school terms. RESULTS: In spite of intensive
      recruitment efforts, only 78% of the total 589 children were enrolled in the
      pilot; 15% had to be excluded because no response could be obtained from their
      parents. At the end of 12 months, 79% of enrolled children (62% of total) had
      received all three applications. Children did not receive applications because
      they were absent on the days when the dental team were carrying out the screening
      or fluoride varnish applications, were ill, or because the child refused. The
      highest refusal rate was in the pre-school. CONCLUSIONS: Younger children need to
      be targeted if improvement in the oral health of five-year-olds is to be
      achieved, the only dental measure in the Public Health Outcomes Framework, but
      they were less likely to cooperate. More research is needed on approaches to
      maximise participation in community programmes such as this, if they are to
      achieve significant population-level improvements in child dental health.

PMID- 24030011
TI  - Clitoral blood flow in systemic sclerosis women: correlation with disease
      clinical variables and female sexual dysfunction.
AB  - OBJECTIVES: The objectives of this study were to investigate clitoral blood flow
      in SSc women compared with healthy controls and to correlate it with
      microvascular damage and disease clinical variables. We also evaluated the
      correlation between clitoral blood flow and sexual dysfunction. METHODS: Twenty
      two SSc women and 20 healthy controls matched for sex and age were enrolled in
      this study. Baseline Doppler indices of the clitoral artery were measured. Peak
      systolic velocity, end diastolic velocity, resistive index (RI), pulsatile index
      (PI) and systolic/diastolic (S/D) ratio were measured. The female sexual function
      index (FSFI) was used to assess sexual function. RESULTS: The RI and S/D ratio
      were higher (P < 0.0001) in SSc women compared with healthy controls. The PI, RI
      and S/D ratio increased with progression of capillaroscopic damage. The RI and
      S/D ratio were higher (P < 0.01) in women with digital ulcers than in women
      without digital ulcers. No correlation exists between Doppler indices of the
      clitoral artery and age or clinical variables of disease. The FSFI was reduced in
      7 (32%) of 22 SSc women. A negative correlation was observed between both the
      FSFI and RI (R = -0.74, P < 0.0001) and the S/D ratio (R = -0.68, P < 0.0001). A
      negative correlation exists between the RI and all domains of the FSFI score
      except for desire. CONCLUSION: Clitoral blood flow was reduced in SSc women
      compared with healthy controls. Clitoral blood flow was reduced in SSc women with
      digital ulcers and it correlated with capillaroscopic damage progression. A
      negative correlation exists between the RI and S/D ratio and all domains of the
      FSFI score except for desire.

PMID- 24030013
TI  - Nonhuman primates: translational models for predicting antipsychotic-induced
      movement disorders.
AB  - Repeated haloperidol treatment administered to nonhuman primates (NHPs) over
      several months or even years leads to the gradual appearance of drug-induced
      dystonic reactions in the orofacial region (mouth opening, tongue protrusion or
      retraction, bar biting) and in the whole body (writhing of the limbs and trunk,
      bar grasping). The propensity of antipsychotics to induce dystonia in NHPs is not
      correlated with their propensity to induce catalepsy in rodents, suggesting that
      the two types of effects are dissociated and may represent distinct aspects of
      the extrapyramidal symptoms induced by antipsychotics. In view of the clear
      homology to clinically observed phenomena, antipsychotic-induced dystonias in
      antipsychotic-primed NHPs would appear to possess a high degree of translational
      validity. These NHP phenomena could therefore serve as a useful model for
      predicting the occurrence of similar abnormal movements with novel substances
      developed for the treatment of schizophrenia or other psychotic disorders.
      Moreover, the NHP dystonia model could possibly serve as a biomarker for
      substances that will eventually cause tardive dyskinesia in patients. 

PMID- 24030012
TI  - Nerve injury increases GluA2-lacking AMPA receptor prevalence in spinal cords:
      functional significance and signaling mechanisms.
AB  - The glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
      (AMPARs) are critically involved in the excitatory synaptic transmission, and
      blocking AMPARs at the spinal level reverses neuropathic pain. However, little is
      known about changes in the composition of synaptic AMPARs in the spinal dorsal
      horn after peripheral nerve injury. AMPARs lacking the GluA2 subunit are
      permeable to Ca(2+), and their currents show unique inward rectification. We
      found that AMPAR-mediated excitatory postsynaptic currents (AMPAR-EPSCs) of
      spinal dorsal horn neurons exhibited a linear current-voltage relationship in
      control rats, whereas AMPAR-EPSCs of dorsal horn neurons displayed inward
      rectification in rats with spinal nerve injury. In nerve-injured rats, compared
      with control rats, the GluA2 protein level was significantly less in the plasma
      membrane but was greater in the cytosolic vesicle fraction in the dorsal spinal
      cord. However, the GluA1 protein levels in these fractions did not differ
      significantly between nerve-injured and control rats. Blocking N-methyl-d
      aspartate receptors (NMDARs) abolished inward rectification of AMPAR-EPSCs of
      dorsal horn neurons in nerve-injured rats. Furthermore, inhibition of calpain or
      calcineurin, but not protein kinase C, completely blocked nerve injury-induced
      inward rectification of AMPAR-EPSCs of dorsal horn neurons. In addition, blocking
      GluA2-lacking AMPARs at the spinal cord level reduced nerve injury-induced pain
      hypersensitivity. Our study suggests that nerve injury increases GluA2
      internalization and the prevalence of GluA2-lacking AMPARs in the spinal dorsal
      horn to maintain chronic neuropathic pain. Increased prevalence of spinal GluA2
      lacking AMPARs in neuropathic pain is mediated by NMDARs and subsequent
      stimulation of calpain and calcineurin signaling. 

PMID- 24030014
TI  - Ce4Ag3Ge4O(0.5)--chains of oxygen-centered [OCe2Ce(2/2)] tetrahedra embedded in a
      [CeAg3Ge4] intermetallic matrix.
AB  - The oxidation of an intermetallic phase under high-pressure/high-temperature
      conditions led to the synthesis of Ce4Ag3Ge4O(0.5) exhibiting [OCe2Ce(2/2]
      tetrahedral chains, in which the oxygen atoms statistically occupy the
      tetrahedral centres. Starting from a 1:1:1 CeAgGe precursor (NdPtSb type), a
      multianvil high-pressure/high-temperature experiment at 11.5 GPa and 1250-1300 
      degrees C revealed Ce4Ag3Ge4O(0.5), crystallizing in the space group Pnma with
      the following lattice parameters: a = 2087.3(4), b = 439.9(1), and c = 1113.8(2)
      pm. Magnetic measurements showed Curie-Weiss behavior above 100 K with an
      experimental magnetic moment of 2.42 uB per Ce atom, close to the value for the
      free Ce(3+) ion, clearly indicating trivalent cerium in Ce4Ag3Ge4O(0.5). Full
      potential GGA+U band structure calculations resulted in metallic properties and a
      magnetic ground state with one unpaired 4f-electron per cerium in agreement with
      the experiments.

PMID- 24030015
TI  - Jumonji and cardiac fate.

PMID- 24030016
TI  - Why has it taken so long to learn what we still don't know?

PMID- 24030017
TI  - Forgetting to switch off SMAD2 in aneurysmal disease.

PMID- 24030018
TI  - Do not overcharge the system or it will explode!: how mitochondrial uncoupling
      protein 2 maintains endothelial function.

PMID- 24030019
TI  - Identifying single S-nitrosothiol sites with cardioprotection.

PMID- 24030020
TI  - Did a classic preconditioning study provide a clue to the identity of the
      mitochondrial permeability transition pore?

PMID- 24030021
TI  - Direct cardiac reprogramming: from developmental biology to cardiac regeneration.
AB  - Heart disease affects millions worldwide and is a progressive condition involving
      loss of cardiomyocytes. The human heart has limited endogenous regenerative
      capacity and is thus an important target for novel regenerative medicine
      approaches. Although cell-based regenerative therapies hold promise, cellular
      reprogramming of endogenous cardiac fibroblasts, which represent more than half
      of the cells in the mammalian heart, may be an attractive alternative strategy
      for regenerating cardiac muscle. Recent advances leveraging years of
      developmental biology point to the feasibility of generating de novo
      cardiomyocyte-like cells from terminally differentiated nonmyocytes in the heart
      in situ after ischemic damage. Here, we review the progress in cardiac
      reprogramming methods and consider the opportunities and challenges that lie
      ahead in refining this technology for regenerative medicine. 

PMID- 24030024
TI  - Circulation research thematic synopsis diabetes and obesity.

PMID- 24030022
TI  - Patching the heart: cardiac repair from within and outside.
AB  - Transplantation of engineered tissue patches containing either progenitor cells
      or cardiomyocytes for cardiac repair is emerging as an exciting treatment option
      for patients with postinfarction left ventricular remodeling. The beneficial
      effects may evolve directly from remuscularization or indirectly through
      paracrine mechanisms that mobilize and activate endogenous progenitor cells to
      promote neovascularization and remuscularization, inhibit apoptosis, and
      attenuate left ventricular dilatation and disease progression. Despite
      encouraging results, further improvements are necessary to enhance current tissue
      engineering concepts and techniques and to achieve clinical impact. Herein, we
      review several strategies for cardiac remuscularization and paracrine support
      that can induce cardiac repair and attenuate left ventricular dysfunction from
      both within and outside the myocardium. 

PMID- 24030025
TI  - Concurrent and simultaneous polydrug use among young Swiss males: use patterns
      and associations of number of substances used with health issues.
AB  - BACKGROUND: Simultaneous polydrug use (SPU) may represent a greater incremental
      risk factor for human health than concurrent polydrug use (CPU). However, few
      studies have examined these patterns of use in relation to health issues,
      particularly with regard to the number of drugs used. METHODS: In the present
      study, we have analyzed data from a representative sample of 5734 young Swiss
      males from the Cohort Study on Substance Use Risk Factors. Exposure to drugs
      (i.e., alcohol, tobacco, cannabis, and 15 other illicit drugs), as well as
      mental, social and physical factors, were studied through regression analysis.
      RESULTS: We found that individuals engaging in CPU and SPU followed the known
      stages of drug use, involving initial experiences with licit drugs (e.g., alcohol
      and tobacco), followed by use of cannabis and then other illicit drugs. In this
      regard, two classes of illicit drugs were identified, including first uppers,
      hallucinogens and sniffed drugs; and then "harder" drugs (ketamine, heroin, and
      crystal meth), which were only consumed by polydrug users who were already taking
      numerous drugs. Moreover, we observed an association between the number of drugs
      used simultaneously and social issues (i.e., social consequences and
      aggressiveness). In fact, the more often the participants simultaneously used
      substances, the more likely they were to experience social problems. In contrast,
      we did not find any relationship between SPU and depression, anxiety, health
      consequences, or health. CONCLUSIONS: We identified some associations with SPU
      that were independent of CPU. Moreover, we found that the number of concurrently
      used drugs can be a strong factor associated with mental and physical health,
      although their simultaneous use may not significantly contribute to this
      association. Finally, the negative effects related to the use of one substance
      might be counteracted by the use of an additional substance.

PMID- 24030026
TI  - Coexistence of testicular microlithiasis with parathyroid adenoma in an obese
      child.

PMID- 24030027
TI  - Zellweger syndrome: prenatal and postnatal growth failure with epiphyseal
      stippling.
AB  - We present a 2-month-old male affected by Zellweger syndrome, a rare peroxisomal
      disorder. The diagnosis was supported by clinical and radiological findings and
      established by biochemical tests. The characteristic radiological features
      included anomalous ossification (epiphyseal stippling). We also discuss main
      differential diagnoses of epiphyseal stippling and a brief literature review.

PMID- 24030028
TI  - Premature thelarche related to fennel tea consumption?
AB  - BACKGROUND: Isolated premature thelarche is the breast development in the absence
      of other secondary sex characteristics in prepubertal girls. Fennel is a plant
      which contains a phytoestrogen called anethole as an active ingredient. CASE:
      Here, we report a case of a 12-month-old girl who showed breast development that
      became apparent in the last 3 months. Her medical history revealed that she was
      given two to three teaspoons of fennel tea by her mother every day for
      restlessness for the last 6 months. Isolated premature thelarche was diagnosed
      based on physical and laboratory findings. On follow-up, after cessation of
      fennel consumption, the breast development of the patient regressed gradually and
      became normal by the end of 1 year. CONCLUSION: Reporting this case, we want to
      emphasize the importance of awareness of fennel tea, a commonly used plant in
      babies, as a preventable cause of premature thelarche.

PMID- 24030023
TI  - Protein engineering for cardiovascular therapeutics: untapped potential for
      cardiac repair.
AB  - A number of new and innovative approaches for repairing damaged myocardium are
      currently undergoing investigation, with several encouraging results. In addition
      to the progression of stem cell-based approaches and gene therapy/silencing
      methods, evidence continues to emerge that protein therapeutics may be used to
      directly promote cardiac repair and even regeneration. However, proteins are
      often limited in their therapeutic potential by short local half-lives and
      insufficient bioavailability and bioactivity, and many academic laboratories
      studying cardiovascular diseases are more comfortable with molecular and cellular
      biology than with protein biochemistry. Protein engineering has been used broadly
      to overcome weaknesses traditionally associated with protein therapeutics and has
      the potential to specifically enhance the efficacy of molecules for cardiac
      repair. However, protein engineering as a strategy has not yet been used in the
      development of cardiovascular therapeutics to the degree that it has been used in
      other fields. In this review, we discuss the role of engineered proteins in
      cardiovascular therapies to date. Further, we address the promise of applying
      emerging protein engineering technologies to cardiovascular medicine and the
      barriers that must be overcome to enable the ultimate success of this approach. 

PMID- 24030029
TI  - A novel insertion in the FOXL2 gene in a Chilean patient with blepharophimosis
      ptosis epicanthus inversus syndrome type I.
AB  - OBJECTIVE: A novel insertion in the forkhead transcription factor 2 (FOXL2) was
      identified in a Chilean patient with blepharophimosis, ptosis, and epicanthus
      inversus syndrome associated with premature ovarian failure (BPES type I). A
      clinical and molecular characterization of a patient with BPES type I was
      performed. METHOD: We present a 16-year-old adolescent girl with surgically
      treated blepharophimosis, ptosis, and epicanthus inversus that was associated
      with delayed puberty and secondary amenorrhea at the age of 15, indicators that
      suggested that the patient had BPES type I. The FOXL2 gene was analyzed by
      sequencing its coding region. RESULTS: The sequence analysis of the FOXL2 gene
      revealed a novel heterozygous mutation: an 11 bp duplication (c.901_911dup11)
      that was predicted to encode a truncated protein (p.Pro305Argfs*54). CONCLUSIONS:
      A novel out-of-frame duplication following the polyalanine domain in the FOXL2
      gene was identified in a Chilean patient with BPES type I. This study
      characterized the molecular alterations in FOXL2 and confirmed the diagnosis,
      thereby providing information to allow for improved genetic counseling for the
      patient and her family.

PMID- 24030030
TI  - X-linked recessive nephrogenic diabetes insipidus: a clinico-genetic study.
AB  - A retrospective genotype and phenotype analysis of X-linked congenital
      nephrogenic diabetes insipidus (NDI) was conducted on a nationwide cohort of 25
      (24 male, 1 female) Korean children with AVPR2 gene mutations, comparing non
      truncating and truncating mutations. In an analysis of male patients, the median
      age at diagnosis was 0.9 years old. At a median follow-up of 5.4 years, urinary
      tract dilatations were evident in 62% of patients and their median glomerular
      filtration rate was 72 mL/min/1.73 m2. Weights and heights were under the 3rd
      percentile in 22% and 33% of patients, respectively. One patient had low
      intelligence quotient and another developed end-stage renal disease. No
      statistically significant genotype-phenotype correlation was found between non
      truncating and truncating mutations. One patient was female; she was analyzed
      separately because inactivation and mosaicism of the X chromosome may influence
      clinical manifestations in female patients. Current unsatisfactory long-term
      outcome of congenital NDI necessitates a novel therapeutic strategy.

PMID- 24030031
TI  - Body composition in young patients with galactose metabolic disorders: a
      preliminary report.
AB  - AIM: Body composition evaluation in patients with galactosemia and its variants.
      METHODS: The body composition of young subjects with galactose metabolic
      disorders was analyzed with dual X-ray absorptiometry. The subjects were divided
      into the classic galactosemia (CG; n=14) group and the group with other galactose
      metabolic disorders (OGMD, e.g., epimerase deficiency; n=8). RESULTS: In both
      groups, bone strength and bone mineral density Z-scores were normal. However, CG
      patients appeared sarcopenic (median muscle mass Z-score=-1.93), whereas OGMD
      subjects had low-normal muscle mass. In addition, approximately half of all
      patients were overweight. In CG patients, bone mass was strongly correlated to
      muscle mass (r=0.81), whereas in OGMD patients it was positively correlated to
      body mass index (r=0.78). CONCLUSIONS: An imbalance between muscle and fat mass,
      especially in patients with classic galactosemia, was observed. Given the
      observed strong correlation between bone and muscle mass, more effective
      lifestyle counseling is needed.

PMID- 24030032
TI  - Shear-related fibrillogenesis of fibronectin.
AB  - Biomechanical forces can induce the transformation of fibronectin (Fn) from its
      compact structure to an extended fibrillar state. Adsorption of plasma proteins
      onto metallic surfaces may also influence their conformation. We used a cone
      plate rheometer to investigate the effect of shear and stainless steel on
      conformational changes of Fn. In control experiments, cones grafted once or twice
      with polyethylene glycol were used. Plasma Fn was added at concentrations of 50
      or 100 MUg/ml to bovine serum albumin (BSA)- or Fn-coated plates and subsequently
      exposed to dynamic shear rates stepwise increasing from 50 to 5000 s-1 within 5
      min and subsequently decreasing from 5000 to 50 s-1 within 5 min. The viscosity
      (mPa s) of Fn solutions was recorded over 10 min. Upon exposure to shear, the
      viscosity in the sample increased, suggesting conformational changes in Fn.
      Western blotting and densitometric analyses demonstrated that conformational
      changes of plasma Fn depended both on shear and protein concentration. However,
      there was no significant difference in fibril formation between BSA- or Fn-coated
      plates, suggesting that physical properties of stainless steel and biomechanical
      forces such as shear can affect the molecular structure of Fn. Our model may
      provide useful information of surface- and flow-induced alterations of plasma
      proteins.

PMID- 24030033
TI  - Alteration of travel patterns with vision loss from glaucoma and macular
      degeneration.
AB  - IMPORTANCE: The distance patients can travel outside the home influences how much
      of the world they can sample and to what extent they can live independently.
      Recent technological advances have allowed travel outside the home to be directly
      measured in patients' real-world routines. OBJECTIVE: To determine whether
      decreased visual acuity (VA) from age-related macular degeneration (AMD) and
      visual field (VF) loss from glaucoma are associated with restricted travel
      patterns in older adults. DESIGN: Cross-sectional study. SETTING: Patients were
      recruited from an eye clinic, while travel patterns were recorded during their
      real-world routines using a cellular tracking device. PARTICIPANTS: Sixty-one
      control subjects with normal vision, 84 subjects with glaucoma with bilateral VF
      loss, and 65 subjects with AMD with bilateral or severe unilateral loss of VA had
      their location tracked every 15 minutes between 7 am and 11 pm for 7 days using a
      tracking device. MAIN OUTCOMES AND MEASURES: Average daily excursion size
      (defined as maximum distance away from home) and average daily excursion span
      (defined as maximum span of travel) were defined for each individual. The effects
      of vision loss on travel patterns were evaluated after controlling for individual
      and geographic factors. RESULTS: In multivariable models comparing subjects with
      AMD and control subjects, average excursion size and span decreased by
      approximately one-quarter mile for each line of better-eye VA loss (P <= .03 for
      both). Similar but not statistically significant associations were observed
      between average daily excursion size and span for severity of better-eye VF loss
      in subjects with glaucoma and control subjects. Being married or living with
      someone and younger age were associated with more distant travel, while less
      distant travel was noted for older individuals, African Americans, and those
      living in more densely populated regions. CONCLUSIONS AND RELEVANCE: Age-related
      macular degeneration-related loss of VA, but not glaucoma-related loss of VF, is
      associated with restriction of travel to more nearby locations. This constriction
      of life space may impact quality of life and restrict access to services.

PMID- 24030034
TI  - Somatic cell transformation into stem cell-like cells induced by different
      microenvironments.
AB  - Development of induced pluripotent stem cell (iPSC) technology introduced a novel
      way to derive pluripotent stem cells, but the genetic manipulation required to
      generate iPSCs may lead to uncontrolled tumorigenesis of the established cells
      and thus limit clinical feasibility of the technology. Numerous attempts have
      been made to date, and alternative reprogramming of somatic cells to reactivate
      cellular plasticity after differentiation has been suggested. As a result, it had
      become clear that cell-to-cell interactions and specific acellular environments
      can be utilized for somatic cell reprogramming. In our previous studies,
      embryonic stem cell (ESC)-like cells could be derived from transforming ovarian
      cells and fetal fibroblasts by cell-to-cell interaction or specific cell-mediated
      microenvironmental factor(s). This cellular event was induced without undertaking
      genetic manipulation of progenitor cells. Several differences were found between
      the cellular properties of niche-induced, ESC-like cells and those of genetically
      manipulated iPSCs and the referenced ESCs. Thus, we provided evidence that
      terminally differentiated somatic cells either acquire pluripotency-like activity
      or possess cellular and genetic plasticity under a specific microenvironment
      and/or cell-to-cell interaction. In this minireview, we discuss derivation of
      stem cell-like cells under specific microenvironmental conditions in terms of
      technical perspectives and limitations. 

PMID- 24030035
TI  - Participation in productive activities and health outcomes among older adults in
      urban China.
AB  - PURPOSE OF THE STUDY: This study examined whether participating in productive
      activities was associated with better health outcomes among older adults in urban
      China, including analysis of potential gender differences. DESIGN AND METHODS:
      Using a sample of 10,016 urban Chinese adults aged 60 years or older from the
      2006 Sample Survey of the Aged Population in Urban/Rural China, we regressed
      measures of self-rated health, functional health, and depression on productive
      activities (paid employment, helping with family, and volunteering), controlling
      for sociodemographic variables. RESULTS: Those who provided assistance to family
      members or volunteered had significantly lower levels of depression and better
      functional and self-rated health than their counterparts. Older adults with paid
      job, providing family assistance, or volunteering reported significantly lower
      levels of depression and better functional and self-rated health than those
      without those activities. However, only older men with paid employment reported
      significantly less depression, and the effect of family assistance on functional
      health also differed by gender. IMPLICATIONS: As research increasingly
      demonstrates the role of productive activities in maintaining health among older
      adults, our findings can help practitioners or policy makers strategically select
      or develop health programs to promote productive activities among older adults in
      urban China.

PMID- 24030036
TI  - Impact of social factors on the quality of life of patients with refractory
      epilepsy.
AB  - PURPOSE: To assess the impact of social factors on the quality of life of
      Bulgarian patients with refractory epilepsy. CASE REPORT: We have studied 70
      patients with refractory epilepsy (RE) and 70 patients with pharmacosensitive
      epilepsy. All of them were between 18 and 65 years of age, without cognitive
      decline, progressive somatic or neurological disease or recent seizures. All
      participants were inquired about their education,employment, marital status, and
      driving. Only the patients with RE completed QOLIE-89. RESULTS: Twenty-five
      (35.71%) of the participants with RE were not married; 16 (22.86%) of them had an
      elementary education, 44 (62.86%) - a secondary education, and 10 (14.29%) - a
      university education.Nineteen (27.4%) participants were employed, 41 (58.57%)
      were recognized disabled, 10 (14.29%)were unemployed. Two (2.86%) of the patients
      with RE were drivers. We found out that the marital status did not change the
      quality of life. The university education correlated with a higher assessment of
      the "overall health" subscale (50%). The limited or lacking employment had a
      negative impact on the assessment of the following subscales: "pain", "health
      discouragement", "sexual relations", "emotional well-being", "memory",
      "work/driving/social function", "overall health", "overall quality of life" and
      the overall score of QOLIE-89. The possibility of driving correlated with more
      worries about adverse events from antiepileptic drugs. CONCLUSION: The limited or
      lacking employment has a negative impact on most aspects of the quality of life,
      while education and driving influence single aspects of the quality of life.

PMID- 24030037
TI  - High cervical spinal schwannoma; microneurosurgical management: an experience of
      15 cases.
AB  - PURPOSE: Schwannoma arising from high cervical spinal root are common among the
      spinal schwannomas.Here, we prospectively recorded the clinical features,
      radiological features, surgical approaches & findings,postoperative follow up &
      ultimate neurological outcome of high cervical spinal schwannomas and then we
      evaluated the records retrospectively. METHOD: Here, schwannomas arising from C1,
      C2 and C3 spinal nerve roots were regarded as high cervical spinal schwannoma.
      All patients with high cervical spinal schwannomas that were consecutively
      operated micro-neurosurgically from 2006-2010 were included in the study.
      Postoperatively all patients were followed up regularly both clinically and neuro
      radiologically (MRI of cervical spine). RESULTS: Average follow up was 31.5
      months. The mean age of the series was 35.8 years (range 10-61 years). There were
      8 male and 7 female patients. The mean duration of symptoms at the time of
      presentation was 32 months (range 06 months-5 years). Two schwannomas were
      completely extradural, seven were intradural and rest six were interdural or
      hourglass type (both extra and intradural) as identified during surgery. The
      standard midline posterior approach was used in all patients. A C2
      hemilaminectomyor C2 laminectomy with or without cutting of posterior arch of
      atlas was used for most intradural and large interdural C2 schwannomas. Tumor
      removal was complete in all cases. Preservation of the nerve root fibers was not
      possible in 9 cases and was possible only in 3 cases. In two patients CSF leak
      developed after operation. One patient who had severe myelopathic features with
      bed sore failed toimprove and expired 5 months after operation. Rest of the
      patients showed postoperative improvement in their preoperative symptoms and
      returned to their normal life by the end of sixth month. There was no tumor
      recurrence in any patient till last follow up. CONCLUSION: Proper 3-D anatomical
      orientation & physiological knowledge, deep neuro-radiological
      observation,pathological appreciations and micro-neurosurgical skill and
      expertization can make the surgical management of these tumors ( in a surgically
      complex site) simple with gratifying result (i.e.neurological outcome) without
      extensive bone removal or soft tissue manipulation through a standard midline
      posterior approach.

PMID- 24030038
TI  - Systemic lupus erythematosus presented as extensive longitudinal myelitis.
AB  - BACKGROUND: longitudinal myelitis (LM) is defined by the continuous lesion of
      more than four spinal cord segments. LM is a rare variant of acute transverse
      myelitis and it frequently presented poor responses to immunomodulatory therapy,
      which resulted in severe and disabling sequelae. We reported a case of acute
      longitudinal myelitis involving extensive lesions from cervical spinal cord to
      conus medullaris caused by newly diagnosed SLE. CASE REPORT: A 39 years old man
      who was previously healthy presented to our hospital due to acute urinary
      retention with progressive lower limb weakness for a week. Brisk deep tendon
      reflexes in upper limbs and decreased reflexes in lower limbs were noted on
      admission. The pin-prick, vibration, and light touch sensations were decreased in
      the lower limbs. Spinal MRI sagittal view showed an T2WI bright up mass in the
      spinal cord below C3/4 level with extension to conus medullaris. He was diagnosed
      SLE based on ARA criteria. After ruling out mimics including NMO and MS, SLE with
      LM explained what happened to him . CONCLUSION: Given the poor prognosis of SLE
      with LM, which resulted in severe and disabling sequelae. More comprehensive
      understand of the disease course, real mechanisms and treatment strategy are
      needed.

PMID- 24030039
TI  - Vestibular paroxysmia associated with paroxysmal pulsatile tinnitus: a case
      report and review of the literature.
AB  - PURPOSE: Vestibular paroxysmia is defined as paroxysmal, brief, and carbamazepine
      responsive vertigo. Although neurovascular cross-compression (NVCC) of the
      vestibulocochlear nerve is believed to be the cause of vestibular paroxysmia, the
      mechanism remains controversial. Herein, we describe the case of a man with NVCC
      who presented with paroxysmal vertigo associated with paroxysmal pulsatile
      tinnitus. CASE REPORT: A 68-year-old man presented with paroxysmal vertigo for
      one month. Paroxysmal pulsatile tinnitus in the right ear occurred simultaneously
      with the vertigo. Magnetic resonance imaging demonstrated that the right anterior
      inferior cerebellar artery was compressing the right vestibulocochlear nerve. The
      vertigo and tinnitus completely disappeared within one week after treatment with
      carbamazepine. CONCLUSION: The pulsatile nature of the patient's tinnitus implied
      that the auditory nerve was being compressed by a pulsating artery and was found
      to consolidate the causal relationship between NVCC and vestibular paroxysmia.

PMID- 24030040
TI  - Sudden death due to medulloblastoma: a case report.
AB  - PURPOSE: Medulloblastoma is one of the notorious CNS malignancies for subtle and
      atypical clinical presentations, causing rapid neurological deterioration and
      death, especially in pediatric patients. The delay in diagnosis leads to painful
      remorse, conflicts, and lawsuits for parents and medical staff. CASE REPORT: We
      report a 2 year old girl with initial presentation of febrile pyuria. Soon after
      admission, a generalized clonic-tonic seizure attacked to her and led to an
      impression of febrile convulsion. However, an unusual postical slowness of pupils
      to light stimulation propelled a further investigation. A contrast enhanced brain
      computer tomography (CT) unexpectedly showed a mass occupied the fourth ventricle
      resulting in obstructive hydrocephalus and compressed adjacent brain stem and
      cerebellum. The disease rapidly progressed and she died 18 hours after an
      emergent decompression with extraventricular drainage (EVD) installation.
      Cytology of cerebrospinal fluid proved medulloblastoma. CONCLUSION: This case
      report highlights the importance of clinical suspicion, such as a trivial but
      unusual presentation, a lagged pupil response to light stimulation. A brain CT
      scan should be done to rule out any possibility of an organic lesion. Close
      monitor is required in order to catch and treat medulloblastoma early. However,
      once discovered, the cancer has spread.

PMID- 24030041
TI  - Sjogren's syndrome with acute cerebellar ataxia and massive lymphadenopathy : a
      case report.
AB  - PURPOSE: Common etiologies of acute acquired cerebellar ataxia include
      cerebrovascular diseases, toxin or drugs, infections/para-infections, and
      autoimmune diseases. It is a rare manifestation of Sjogren's syndrome, which is a
      common autoimmune disease but is often missed as a differential diagnosis. CASE
      REPORT: This is a report of a patient with acute onset cerebellar ataxia for one
      month. She also had massive neck lymphadenopathy. After a series of studies and
      the exclusion of other common causes of acute cerebellar ataxia, she was
      diagnosed as having Sjogren's syndrome. Patients with Sjogren's syndrome have
      higher risk for lymphoma, which leads to poorer prognosis. After lymph node
      biopsy, the patient was proven to have sinus histiocytosis, which is another rare
      finding in Sjogren's syndrome. DISCUSSION: For patients with acute acquired
      cerebellar ataxia, immune-mediated cerebellar ataxia should be an important
      differential diagnosis aside from the more common causes like stroke or drugs.

PMID- 24030042
TI  - A novel variant mutation of transthyretin Ile73Val-related amyloidotic
      polyneuropathy in Taiwanese.
AB  - PURPOSE: Familial amyloidotic polyneuropathy (FAP) is an inherited disease caused
      by deposition of mutant amyloid proteins in the peripheral nerves. Abnormal
      transthyretin (TTR) accounts for protein aggregation in the majority of FAP.
      Val30Met is the most common TTR gene-mutation reported in different ethnic
      populations. In Taiwan, Ala97Ser mutation is probably a major hot-spot of TTR
      mutations. On the other hand, Ile73Val mutation was only reported in one
      Bangladeshi family. We reported here the first patient of amyloidotic
      polyneuropathy with Ile73Val TTR mutation in Taiwan. CASE REPORT: This patient
      had symptoms and signs of sensory motor polyneuropathy and early gastrointestinal
      autonomic dysfunction since around 50 years old. A nerve conduction velocity
      (NCV) study showed typical axonal sensory-motor polyneuropathy. A standard
      autonomic function test revealed orthostatic hypotension and was compatible with
      cardiovascular autonomic dysfunction. There was also impaired sudomotor activity.
      An echocardiogram study suggested amyloidotic restrictive cardiomyopathy. A
      genetic analysis revealed Ile73Val TTRR mutation. CONCLUSION: We reported the
      first patient with Ile73Val TTR mutation in Taiwan, who had earlier
      gastrointestinal dysfunction. Similar to the Bangladeshi patient reported in the
      previous article, painful neuropathy, a feature typically presented in more
      common TTR gene mutations, is absent.

PMID- 24030043
TI  - Pneumocephalus associated with massive cerebral air embolism.
AB  - A 61-year-old man with critical aortic stenosis underwent aortic valve
      replacement. Mechanical ventilation was applied because of postoperative acute
      pulmonary edema accompanied by poor ventilation and poor oxygenation, and the
      patient was also recannulized to an extracorporeal membranous oxygenator.
      Bilateral pneumothorax was found 2 days later, and the right upper and left lower
      chest quadrants were drained with pigtail catheters. The patient did not regain
      consciousness 5 days after cessation of propofol. He remained in a deep coma;
      anisocoric pupils without light reflex and left upward eyeball deviation were
      observed. The brain computed tomography (CT) scan revealed cerebral air embolism
      that caused extensive cerebral infarction accompanied by a hypodense lesion
      located in the bilateral cerebral and cerebellar hemispheres, mainly on the right
      side; mass effect and midline shifting were observed (Figs. 1 and 2). The bone
      window image of brain CT scan revealed no evidence of fracture or bony lesion
      over the skull base or ethmoid sinus. The patient expired later and an autopsy
      was not obtained. Cerebral air embolism is mostly due to invasive vascular
      procedure like cardiosurgical procedure(1), angiography(2) or central venous
      catheterization(3). Besides, neurosurgeries, barotraumas, basilar skull
      fractures, sinus fractures, congenital skull defects, neoplasm, gas producing
      organism infections, epidural anaesthesia or even lumbar puncture had been
      reported(4,5). Massive cerebral air embolism is rare within most of the reported
      cases. Our case demonstrated an air embolism associated with large air pockets in
      the cerebral parenchyma and Virchow-Robin space. The interesting aspect of this
      case lies in the image of a peculiar pattern of massive cerebral air embolism
      with air in the carotid artery, as well as in the small cerebral arteries and
      leaking into the brain parenchyma. The latter is likely the result of breakdown
      of the blood-brain barrier after cerebral infarction. 

PMID- 24030044
TI  - Stent-assisted recanalization in acute basilar artery occlusion.

PMID- 24030045
TI  - Generation of mice with conditional ablation of the Cd40lg gene: new insights on
      the role of CD40L.
AB  - CD40 ligand (CD40L) acts as an immune modulator in activated T cells, and
      mutations in the extracellular domain are associated to X-linked hyper IgM
      syndrome. A role for platelet CD40L in mediating thrombotic and inflammatory
      processes in atherosclerosis has also been reported. Using the Cre/loxP
      recombination technology we generated four knockout lines of mice with deletion
      of the Cd40lg gene restricted to the hematopoietic system. Mouse lines with
      expression of Cre recombinase driven by the Tie2, Vav1, or CD4 promoters showed
      in vivo ablation of CD40L in leukocytes and platelets. In contrast, in mice with
      Cre expression driven by the megakaryocyte lineage-restricted Pf4 promoter,
      abolition of CD40L expression was observed in megakaryocytes cultured in vitro,
      but not in circulating platelets. Characterization of these animals revealed
      reduced in vivo thrombogenesis and defective activation of washed CD40L-deficient
      platelets, suggesting that membrane-bound CD40L is involved in the control of
      haemostasis acting as a platelet co-activator. In addition, we report the
      practically absence of CD40L in mouse and human endothelial cells, as well as the
      detection of an exon 3-deleted CD40L transcript in both platelets and leukocytes
      of mouse and human origin. Finally, compared with their corresponding littermate
      floxed controls, Cre+ mice carrying CD40-deficient leukocytes did not exhibit
      increased IgM levels, and reduction of IgA and IgG levels was statistically
      significant only in Tie2-Cre+ mice, suggesting that expression of CD40L in an
      earlier developmental step may be determinant in the regulation of the class
      switch recombination process. 

PMID- 24030046
TI  - Towards a more open debate about values in decision-making on agricultural
      biotechnology.
AB  - Regulatory decision-making over the use of products of new technology aims to be
      based on science-based risk assessment. In some jurisdictions, decision-making
      about the cultivation of genetically modified (GM) plants is blocked supposedly
      because of scientific uncertainty about risks to the environment. However,
      disagreement about the acceptability of risks is primarily a dispute over
      normative values, which is not resolvable through natural sciences. Natural
      sciences may improve the quality and relevance of the scientific information used
      to support environmental risk assessments and make scientific uncertainties
      explicit, but offer little to resolve differences about values. Decisions about
      cultivating GM plants will thus not necessarily be eased by performing more
      research to reduce scientific uncertainty in environmental risk assessments, but
      by clarifying the debate over values. We suggest several approaches to reveal
      values in decision-making: (1) clarifying policy objectives; (2) determining what
      constitutes environmental harm; (3) making explicit the factual and normative
      premises on which risk assessments are based; (4) better demarcating
      environmental risk assessment studies from ecological research; (5) weighing the
      potential for environmental benefits (i.e., opportunities) as well as the
      potential for environmental harms (i.e., risks); and (6) expanding participation
      in the risk governance of GM plants. Recognising and openly debating differences
      about values will not remove controversy about the cultivation of GM plants.
      However, by revealing what is truly in dispute, debates about values will clarify
      decision-making criteria. 

PMID- 24030047
TI  - Influence of the hand squeeze and mask distensibility on tidal volume
      measurements during neonatal mask ventilation.
AB  - BACKGROUND: During mask ventilation, the mask volume can vary as it is
      pressurized or when it is squeezed. The change in volume of the mask may affect
      tidal volumes delivered and difference in inspired (Vti) and expired tidal
      volumes (Vte). OBJECTIVES: To investigate whether hand squeeze and distensibility
      of the mask during ventilation influences tidal volume measurements. METHODS: For
      both experiments, we ventilated a leak-free mask ventilation model using
      pressures of 25/5 cm H2O through a t-piece. Vti and Vte were measured. (A) Two
      consultants performed mask ventilation with (1) consistent hand squeeze, (2)
      release during inflation and squeeze during expiration, (3) squeeze during
      inflation, release during expiration, and (4) gentle squeeze. RESULTS: (B) Thirty
      caregivers performed mask ventilation. Experiment A: Vti was different during
      consistent hold (1) 8.1 ml (0.4) and loose grip (4) 8.2 ml (0.3), compared to
      squeezing during inflation (2) 18.9 ml (1.9), or expiration (3) 6.4 ml (3.5).
      Variance in difference between Vti and Vte occurred only when the mask was
      squeezed during inflation (-47.4% (101.5)). Experiment B: volumes measured were
      consistent (intraindividual CV 3-5%, interindividual CV 9-10%). When comparing
      gas flow rate of 6-10 l/min, volumes increased by approximately 8%, differences
      in Vti and Vte were small with both flow settings (-0.9% (-3.9-1.4) and -0.6% (
      3.3-1.8); n.s.). CONCLUSION: Variation in mask hold during mask ventilation can
      influence volume measurement, but this hardly occurs when testing caregivers.

PMID- 24030048
TI  - MCT1 and MCT4 expression during myocardial ischemic-reperfusion injury in the
      isolated rat heart.
AB  - BACKGROUND/AIMS: Myocardium ischemia-reperfusion (I/R) injury can be caused by
      imbalances in cellular metabolism. Lactate, transported by monocarboxylate
      transporters (MCTs), has been implicated as a mechanism in this process. The
      present study was designed to investigate the expression and functional role of
      MCTs in rat hearts during ischemia and reperfusion. METHODS: Langendorff-perfused
      rat hearts were subjected to 20 minutes stabilization, 30 minutes of global
      ischemia and 60 minutes reperfusion. Hearts were collected serially for detecting
      expression changes in MCT1, MCT4 during myocardial I/R injury and lactate
      concentration was measured. Post-ischemic left ventricular function and infract
      size were determined at end-point, followed by the pretreatment of D-lactate, a
      competitive inhibitor of MCTs. RESULTS: MCT4 was significantly increased
      following global ischemia and MCT1 expression was increased during the early
      stages of reperfusion in isolated rat hearts, while the expression of the
      ancillary protein CD147 was increased during I/R injury. We determined increases
      in AMPK phosphorylation status, which was significantly elevated following
      ischemia and early reperfusion. Blocking monocarboxylate transport by competitive
      inhibition with D-lactate caused decreased left ventricular performance and
      increased infarct size. CONCLUSION: Increased MCT4 expression facilitates lactate
      extrusion during the ischemic period, while increased MCT1 may facilitate lactate
      transport into and out of cells simultaneously during early reperfusion, with
      increases in AMPK phosphorylation status during the myocardial I/R period.
      Lactate transport by MCTs has a profound protective effect during myocardial
      ischemia reperfusion injury.

PMID- 24030050
TI  - Lifelong learning.

PMID- 24030051
TI  - A bioinspired autonomous swimming robot as a tool for studying goal-directed
      locomotion.
AB  - The bioinspired approach has been key in combining the disciplines of robotics
      with neuroscience in an effective and promising fashion. Indeed, certain aspects
      in the field of neuroscience, such as goal-directed locomotion and behaviour
      selection, can be validated through robotic artefacts. In particular, swimming is
      a functionally important behaviour where neuromuscular structures, neural control
      architecture and operation can be replicated artificially following models from
      biology and neuroscience. In this article, we present a biomimetic system
      inspired by the lamprey, an early vertebrate that locomotes using anguilliform
      swimming. The artefact possesses extra- and proprioceptive sensory receptors,
      muscle-like actuation, distributed embedded control and a vision system.
      Experiments on optimised swimming and on goal-directed locomotion are reported,
      as well as the assessment of the performance of the system, which shows high
      energy efficiency and adaptive behaviour. While the focus is on providing a
      robotic platform for testing biological models, the reported system can also be
      of major relevance for the development of engineering system applications. 

PMID- 24030066
TI  - Biomechanical aspects of lower limb torsional deformation correction with the
      Ilizarov external fixator.
AB  - The correction of torsional deformities with the Ilizarov apparatus is
      accompanied by rotational and translational displacement, which affects the
      biomechanics of the bone fragments. Understanding the biomechanical factors will
      assist in designing the optimal treatment strategy and mechanical properties of
      the fixator, thus shortening the duration of treatment and improving the
      outcomes. In order to determine the impact of different types of derotators on
      the kinematics of bone fragments in Ilizarov apparatus, physical models were
      studied. Translational and derotational displacement was measured using non
      contact method (Optotrak Certus Motion Capture System). The results of the
      studies conducted on physical models have shown that regardless of the type of
      the derotator, the divergence between the applied angle of derotation and the
      obtained angle of rotation relative to fragments needs to be taken into account.
      Transverse displacement of fragments occur by 3.5 mm to approximately 9 mm,
      depending on the angle of derotation. For correction of rotational deformities up
      to 30 degrees , it is advisable to use the type Z derotators because of its
      higher accuracy of derotation. Different types of derotators can affect the
      biomechanical conditions in the regenerating bone tissue through different
      kinematics characteristics.

PMID- 24030067
TI  - Microstructured extracellular matrices in tissue engineering and development: an
      update.
AB  - Microstructured extracellular matrix (ECM), which contains heterogeneous features
      of the same size scale (5-100 MUm) as tissue organoids, has become an important
      material for the engineering of functional tissues and for the study of tissue
      level biology. This review describes methods to generate this class of ECM, and
      highlights recent advances in the application of microstructured ECM to problems
      in basic and applied biology. It also discusses computational techniques to
      analyze and optimize the microstructural patterns for a desired functional
      output. 

PMID- 24030068
TI  - Alternative splicing and differential expression of the islet autoantigen IGRP
      between pancreas and thymus contributes to immunogenicity of pancreatic islets
      but not diabetogenicity in humans.
AB  - AIMS/HYPOTHESIS: Thymic expression of self-antigens during T-lymphocyte
      development is believed to be crucial for preventing autoimmunity. It has been
      suggested that G6PC2, the gene encoding islet-specific glucose-6-phosphatase
      catalytic subunit-related protein (IGRP), is differentially spliced between
      pancreatic beta cells and the thymus. This may contribute to incomplete
      elimination of IGRP-specific T lymphocytes in the thymus, predisposing
      individuals to type 1 diabetes. We tested whether specific splice variation in
      islets vs thymus correlates with loss of tolerance to IGRP in type 1 diabetes.
      METHODS: Expression of G6PC2 splice variants was compared among thymus, purified
      medullary thymic epithelial cells and pancreatic islets by RT-PCR. Differential
      immunogenicity of IGRP splice variants was tested in patients and healthy
      individuals for autoantibodies and specific cytotoxic T lymphocytes using
      radiobinding assays and HLA class I multimers, respectively. RESULTS: Previously
      reported G6PC2 splice variants, including full-length G6PC2, were confirmed,
      albeit that they occurred in both pancreas and thymus, rather than islets alone.
      Yet, their expression levels were profoundly greater in islets than in thymus.
      Moreover, three novel G6PC2 variants were discovered that occur in islets only,
      leading to protein truncations, frame shifts and neo-sequences prone to
      immunogenicity. However, autoantibodies to novel or known IGRP splice variants
      did not differ between patients and healthy individuals, and similar frequencies
      of IGRP-specific cytotoxic T lymphocytes could be detected in both patients with
      type 1 diabetes and healthy individuals. CONCLUSIONS/INTERPRETATION: We propose
      that post-transcriptional variation of tissue-specific self-proteins may affect
      negative thymic selection, although this need not necessarily lead to disease.

PMID- 24030069
TI  - Longitudinal changes in insulin sensitivity and beta cell function between women
      with and without a history of gestational diabetes mellitus.
AB  - AIMS/HYPOTHESIS: The aim of the study was to compare longitudinal changes in
      insulin sensitivity (SI) and beta cell function between women with and without a
      history of gestational diabetes mellitus (GDM). METHODS: The prospective follow
      up cohort included 235 parous non-diabetic Mexican-American women, 93 with and
      142 without a history of GDM. The participants underwent dual-energy x-ray
      absorptiometry, OGTTs and IVGTTs at baseline and at a median of 4.1 years follow
      up. The baseline values and rates of change of metabolic measures were compared
      between groups. RESULTS: At baseline, women with prior GDM (mean age 36.3 years)
      had similar values of SI but higher percentages of body fat and trunk fat (p <=
      0.02), a lower acute insulin response and poorer beta cell compensation
      (disposition index [DI]) (p < 0.0001) than women without GDM (mean age 37.9
      years). During the follow-up, women with GDM had a faster decline in SI (p =
      0.02) and DI (p = 0.02) than their counterparts without GDM, with no significant
      differences in changes of weight or fat (p > 0.50). Adjustment for baseline age,
      adiposity, calorie intake, physical activity, age at first pregnancy, additional
      pregnancies and changes in adiposity during follow-up increased the between-group
      differences in the rates of change of SI and DI (p <= 0.003).
      CONCLUSIONS/INTERPRETATION: Mexican-American women with recent GDM had a faster
      deterioration in insulin sensitivity and beta cell compensation than their parous
      counterparts without GDM. The differences were not explained by differences in
      adiposity, suggesting more deleterious effects of existing fat and/or reduced
      beta cell robustness in women with GDM.

PMID- 24030070
TI  - An experimental test on the probability of extinction of new genetic variants.
AB  - In 1927, J.B.S. Haldane reasoned that the probability of fixation of new
      beneficial alleles is twice their fitness effect. This result, later generalized
      by M. Kimura, has since become the cornerstone of modern population genetics.
      There is no experimental test of Haldane's insight that new beneficial alleles
      are lost with high probability. Here we demonstrate that extinction rates
      decrease with increasing initial numbers of beneficial alleles, as expected, by
      performing invasion experiments with inbred lines of the nematode Caenorhabditis
      elegans. We further show that the extinction rates of deleterious alleles are
      higher than those of beneficial alleles, also as expected. Interestingly, we also
      find that for these inbred lines, when at intermediate frequencies, the fate of
      invaders might not result in their ultimate fixation or loss but on their
      maintenance. Our study confirms the key results from classical population
      genetics and highlights that the nature of adaptation can be complex. 

PMID- 24030071
TI  - Sinus dysfunction after stent implantation in the right coronary artery
      immediately recovered after reflow in the sinus node artery.
AB  - A 67-year-old man who had a history of syncope was admitted because of effort
      angina. The sinus node (SN) was the single blood supply from the right coronary
      artery (RCA). After we implanted 2 everolimus-eluting stents for RCA, slow-flow
      occurred and the SN artery was occluded, and junctional escape rhythm was
      sustained. After the wiring to the occluded SN artery, junctional escape rhythm
      immediately recovered to sinus rhythm, and the patient achieved continuous sinus
      rhythm and stable hemodynamics. Given that acute SN ischemia is a possible cause
      of sinus dysfunction, careful choice of a percutaneous coronary intervention
      strategy should be taken into consideration if the SN artery is the single blood
      supply from the RCA and if syncopal history is present.

PMID- 24030072
TI  - Socioeconomic position and survival after cervical cancer: influence of cancer
      stage, comorbidity and smoking among Danish women diagnosed between 2005 and
      2010.
AB  - BACKGROUND: In an attempt to decrease social disparities in cancer survival, it
      is important to consider the mechanisms by which socioeconomic position
      influences cancer prognosis. We aimed to investigate whether any associations
      between socioeconomic factors and survival after cervical cancer could be
      explained by socioeconomic differences in cancer stage, comorbidity, lifestyle
      factors or treatment. METHODS: We identified 1961 cases of cervical cancer
      diagnosed between 2005 and 2010 in the Danish Gynaecological Cancer database,
      with information on prognostic factors, treatment and lifestyle. Age, vital
      status, comorbidity and socioeconomic data were obtained from nationwide
      administrative registers. Associations between socioeconomic indicators
      (education, income and cohabitation status) and mortality by all causes were
      analysed in Cox regression models with inclusion of possible mediators. Median
      follow-up time was 3.0 years (0.01-7.0). RESULTS: All cause mortality was higher
      in women with shorter rather than longer education (hazard ratio (HR), 1.46; 1.20
      1.77), among those with lower rather than higher income (HR, 1.32; 1.07-1.63) and
      among women aged<60 years without a partner rather than those who cohabited (HR,
      1.60; 1.29-1.98). Socioeconomic differences in survival were partly explained by
      cancer stage and less by comorbidity or smoking (stage- and comorbidity-adjusted
      HRs being 1.07; 0.96-1.19 for education and 1.15; 0.86-1.52 for income).
      CONCLUSION: Socioeconomic disparities in survival after cervical cancer were
      partly explained by socioeconomic differences in cancer stage. The results point
      to the importance of further investigations into reducing diagnosis delay among
      disadvantaged groups.

PMID- 24030073
TI  - MicroRNA-100/99a, deregulated in acute lymphoblastic leukaemia, suppress
      proliferation and promote apoptosis by regulating the FKBP51 and IGF1R/mTOR
      signalling pathways.
AB  - BACKGROUND: MicroRNAs alter multiple cell processes and thus influence tumour
      carcinogenesis and progression. MiR-100 and miR-99a have been reported to be
      aberrantly expressed in acute leukaemia. In this study, we focused on their
      functions in acute lymphoblastic leukaemia (ALL) and the molecular networks in
      which they are involved. METHODS: MiR-100 and miR-99a expression levels were
      measured in acute leukaemia patients by qRT-PCR. Kaplan-Meier analysis and log
      rank tests were used to calculate the survival rate. Three human ALL cell lines
      were studied. Apoptosis and proliferation were analysed using siRNA transfection,
      western blot and flow cytometry. RESULTS: In vivo, miR-100 and miR-99a were down
      regulated in 111 ALL patients, especially in high-risk groups; their expression
      levels were correlated with the patient's 5-year survival. In vitro, the
      restoration of miR-100 and miR-99a in ALL cells suppressed cell proliferation and
      increased dexamethasone-induced cell apoptosis. Ectopic expression of miR-100 and
      miR-99a targeted FK506-binding protein 51 (FKBP51) and, in turn, influenced
      glucocorticoid receptor (GR) activity. Meanwhile, miR-100 and miR-99a
      overexpression inhibited the expression of IGF1R and mTOR and their downstream
      oncogene MCL1. CONCLUSION: MiR-100 and miR-99a have critical roles in altering
      cellular processes by targeting both the FKBP51 and IGF1R/mTOR signalling
      pathways in vitro and might represent a potential novel strategy for ALL
      treatment.

PMID- 24030074
TI  - Leukaemia in young children in the vicinity of British nuclear power plants: a
      case-control study.
AB  - BACKGROUND: Concern about the risk of leukaemia in children living near nuclear
      power plants (NPPs) persists. Previous British analyses have been area based and
      consequently thought to be less effective than case-control studies. METHODS:
      Cases of childhood leukaemia and non-Hodgkin lymphoma (LNHL) born and diagnosed
      in Great Britain between 1962 and 2007, with matched cancer-free controls, were
      analysed by logistic regression to estimate the risk of residential proximity at
      birth and diagnosis to the nearest NPP, adjusting for relevant variables.
      RESULTS: For 9821 children with LNHL under the age of 5 years, the estimated
      extra risk associated with residential proximity to an NPP at birth was negative
      interpolated Odds Ratio (OR) at 5 km was 0.86 (0.49-1.52). The comparison of 10
      618 children with LNHL under five with 16 760 similarly aged children with other
      cancers also gave a negative estimate of the extra risk of residential proximity
      at diagnosis-interpolated OR at 5 km was 0.86 (0.62-1.18). CONCLUSION: Our
      results show little evidence of an increase in risk of LNHL to children aged
      under 5 years from living in the vicinity of an NPP. Risk estimates are
      incompatible with comparable ones published in a recent German case-control
      study.

PMID- 24030076
TI  - Cardiovascular epidemiology: the legacy of sound national and international
      studies.

PMID- 24030075
TI  - HIV and HPV infections and ocular surface squamous neoplasia: systematic review
      and meta-analysis.
AB  - BACKGROUND: The frequency of ocular surface squamous neoplasias (OSSNs) has been
      increasing in populations with a high prevalence of infection with human
      immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and
      infection with human papillomavirus (HPV). We aimed to quantify the association
      between HIV/AIDS and HPV infection and OSSN, through systematic review and meta
      analysis. METHODS: The articles providing data on the association between
      HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and
      EMBASE searched up to May 2013, and through backward citation tracking. The
      DerSimonian and Laird method was used to compute summary relative risk (RR)
      estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified
      with the I(2) statistic. RESULTS: HIV/AIDS was strongly associated with an
      increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12
      studies). The summary RR estimate for the infection with mucosal HPV subtypes was
      3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the
      association between both cutaneous and mucosal HPV subtypes and OSSN; the summary
      RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57
      2.05, I(2)=0.0%), respectively. CONCLUSION: Human immunodeficiency virus
      infection increases the risk of OSSN by nearly eight-fold. Regarding HPV
      infection, only the cutaneous subtypes seem to be a risk factor.

PMID- 24030077
TI  - Recommendations of the Brazilian Society of Cardiac Arrhythmias for holter
      monitoring services.
AB  - BACKGROUND: There are innumerous indicators to assure the quality of a service.
      However, medical competence and the proper performance of a procedure determine
      its final quality. The Brazilian Society of Cardiac Arrhythmias recommends
      minimum parameters necessary to guarantee the excellence of ambulatory
      electrocardiographic monitoring services. OBJECTIVE: To recommend minimum medical
      competences and the information required to issue a Holter monitoring report.
      METHODS: This study was grounded in the concept of evidence-based medicine and,
      when evidence was not available, the opinion of a writing committee was used to
      formulate the recommendation. That committee consisted of professionals with
      experience on the difficulties of the method and management in providing services
      in that area. RESULTS: The professional responsible for the Holter monitoring
      analysis should know cardiovascular pathologies and have consistent formation on
      electrocardiography, including cardiac arrhythmias and their differential
      diagnoses. The report should be written in a clear and objective way. The minimum
      parameters that comprise a Holter report should include statistics of the exam,
      as well as quantification and analysis of the rhythm disorders observed during
      monitoring. CONCLUSION: Ambulatory electrocardiographic monitoring should be
      performed by professionals knowledgeable about electrocardiographic analysis,
      whose report should comprise the minimum parameters mentioned in this document.

PMID- 24030078
TI  - Holiday heart syndrome revisited after 34 years.
AB  - The cardiovascular effects of alcohol are well known. However, most research has
      focused on the beneficial effects (the "French paradox") of moderate consumption
      or the harmful consequences, such as dilated cardiomyopathy, associated with
      heavy consumption over an extended period. An association between the ingestion
      of acute alcohol and onset of cardiac arrhythmias was first reported in the early
      70's. In 1978, Philip Ettinger described "Holiday heart syndrome" (HHS) for the
      first time, as the occurrence, in healthy people without heart disease known to
      cause arrhythmia, of an acute cardiac rhythm disturbance, most frequently atrial
      fibrillation, after binge drinking. The name is derived from the fact that
      episodes were initially observed more frequently after weekends or public
      holidays. Since the original description of HHS, 34 years have passed and new
      research in this field has increased the volume of knowledge related to this
      syndrome. Throughout this paper the authors will comprehensively review most of
      the available data concerning HHS and highlight the questions that remain
      unresolved. 

PMID- 24030079
TI  - CHADS2 score: its predictive capacity in clinical practice.

PMID- 24030080
TI  - Cardiac dysfunction related to cirrhosis.

PMID- 24030081
TI  - Case 4/2013: woman with transposition of the great arteries and delayed
      corrective progress.

PMID- 24030082
TI  - Aortas with three lumina.

PMID- 24030083
TI  - Dextrocardia with situs inversus associated with non-compaction cardiomyopathy.

PMID- 24030084
TI  - Prophylaxis of infective endocarditis: a different Brazilian reality?

PMID- 24030085
TI  - Health social networks as online life support groups for patients with
      cardiovascular diseases.
AB  - The number of patients who use the internet in search for information that might
      improve their health conditions has increased. Among them, those looking for
      virtual environments to share experiences, doubts, opinions, and emotions, and to
      foster relationships aimed at giving and getting support stand out. Therefore,
      there is an increasing need to assess how those environments can affect the
      patients' health. This study was aimed at identifying scientific studies on the
      proliferation and impact of virtual communities, known as health social networks
      or online support groups,directed to cardiovascular diseases, which might be
      useful to patients with certain conditions, providing them with information and
      emotional support. A systematic review of the literature was conducted with
      articles published from 2007 to 2012, related to cardiovascular diseases and
      collected from the following databases: PubMed; Association for Computing
      Machinery(ACM); and Institute of Electrical and Electronics Engineers (IEEE).
      Four articles meeting the inclusion criteria were selected. The results were
      interesting and relevant from the health viewpoint, identifying therapeutic
      benefits, such as provision of emotional support, greater compliance to
      treatment, and information sharing on diseases and on life experiences. 

PMID- 24030087
TI  - Is it reasonable in strictly regulating the use of statins for treatment of
      patients with ischemic stroke and hyperlipidemia?

PMID- 24030086
TI  - Phacopower modulation and the risk for postoperative corneal decompensation: a
      randomized clinical trial.
AB  - IMPORTANCE: In compromised corneas, eg, patients with Fuchs endothelial dystrophy
      (FED), it is of utmost importance to use a phacotechnique that is the least
      traumatic to the corneal endothelium. Furthermore, preoperative patient selection
      is crucial, because unexpected corneal decompensation leads to dissatisfied
      patients. OBJECTIVE: To compare corneal thickness and corneal volume changes
      using torsional and longitudinal phacoemulsification in patients with Fuchs
      endothelial dystrophy (FED) and determine risk factors of postoperative corneal
      decompensation. DESIGN, SETTING, AND PARTICIPANTS: Prospective randomized
      clinical trial of all patients diagnosed with FED and planning to undergo
      cataract surgery for visually significant cataract at a university medical center
      from November 2008 to May 2010. INTERVENTION: Fifty-two eyes with FED and
      visually significant cataract underwent torsional (n = 26) or longitudinal (n =
      26) phacoemulsification. Patients were evaluated preoperatively and 1 day, 1
      week, 1 month, 3 months, and 6 months postoperatively. Visits included best
      spectacle-corrected visual acuity, anterior segment optical coherence tomography
      evaluating central corneal thickness (CCT) and peripheral corneal thickness
      (PCT), and Scheimpflug imaging calculating corneal volume (CV). Randomization
      took place according to stage of FED, nucleus density grade, and age.
      Intraoperatively, ultrasonography time and cumulative dissipated energy were
      recorded. MAIN OUTCOMES AND MEASURES: Central corneal thickness, PCT, and CV.
      RESULTS: Ultrasonography time and cumulative dissipated energy were significantly
      lower in the torsional group for harder nucleus density grades compared with the
      longitudinal group (P = .009 and P = .002, respectively). Peripheral corneal
      thickness at the 6-o'clock position, CCT, and CV were significantly smaller in
      the torsional group 1 day postoperatively (P = .002; P = .03; and P = .004,
      respectively). Changes in PCT at the 12-o'clock position and best spectacle
      corrected visual acuity were not significantly different between the 2 groups (P
      > .05). Preoperative CCT was the only significant predictor of corneal
      decompensation postoperatively (P < .001). Preoperative CCT of 620 um
      corresponded to an odds ratio of 1, meaning no increased risk of developing
      corneal decompensation. For each 10-um increase in preoperative CCT, the odds of
      developing corneal decompensation increased 1.7 times. CONCLUSIONS AND RELEVANCE:
      Torsional phacoemulsification effectively reduces ultrasonography time and
      cumulative dissipated energy compared with longitudinal phacoemulsification in
      patients with FED. However, there were only significant differences in corneal
      thickness and CV changes at 1 day postoperatively in favor of the torsional
      group. Central corneal thickness more than 620 um, measured by noncontact
      pachymetry, leads to an increased risk for corneal decompensation after
      phacoemulsification in patients with FED. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00781027.

PMID- 24030088
TI  - The effect of decreasing statin's dosage on LDL-C levels after target levels
      achieved.
AB  - OBJECTIVE: Evidences from clinical trials had demonstrated that statins reduce
      the risk of cardio-cerebral vascular events. But lipid lowering therapy (LLT) was
      suboptimal in stroke patients and clinically, observation of reducing the dosage
      of statins is common when target low density lipoprotein cholesterol (LDL-C)
      level achieved. We aim to explore the changes in lipid profile after reducing
      statin's dosage when target LDL-C level achieved. METHODS: One hundred and three
      consecutive stroke patients follow up at out-patient clinic (44 women, 59 men)
      were recruited. Twenty two patients had their statin's dosage decreased to half
      while eighty one patients had their initial statin's dosage maintained after
      target LDL-C (less than 100mg/dL) level achieved. Lipid profile before and after
      LLT adjustment were compared. RESULTS: The follow-up LDL-C level was significant
      higher while the percentage of patients with LDL-C level less than 100 mg/dL was
      significant lower in patients with statin's dosage decreased. For all patients,
      regardless the adjustment of LLT, the percentage of patients with LDL-C level
      less than 100 mg/dL was significant lower in follow- up lipid profile comparing
      with the baseline, but only the follow-up total cholesterol and LDL-C level were
      significant higher in the patients group with reduced statin's dosage. No
      significant change was found in follow-up high density-lipoprotein cholesterol
      and triglyceride level in either group. CONCLUSION: More patients had LDL-C level
      more than 100 mg/dL after dosage of statins decreased. We suggested that only for
      absolute contraindication or adverse effects of statins should we adjust LLT, it
      is better to maintain the dosage of statins after target level achieved. The
      impact of lipid profile changed after LLT adjustment on clinical outcomes needs
      further studied.

PMID- 24030089
TI  - Factors associated with poor outcome in patients with major intraoperative
      rupture of intracranial aneurysm.
AB  - PURPOSE: This clinical study was conducted to evaluate factors affecting outcome
      in the cases following major intraoperative rupture (MIOR) of the intracranial
      aneurysms. METHODS: Thirty cases with MIOR in a series of 467 surgeries for
      ruptured aneurysms were enrolled in this study. Clinical parameters, including:
      age, Hunt-Hess grading, Fisher grading, aneurysm size, aneurysm contour,
      operative timing, aneurysm location, and rupture timing were studied and compared
      with the prognosis in this particular cohort. The outcome was evaluated using the
      Glasgow Outcome Scale at least 3 months after surgery. Severe disability,
      vegetative survival, and death were classified as poor outcome. RESULTS: Among
      the 30 cases with MIOR, 11 resulted in poor outcomes (36.7%). Age was an
      important prognostic factor in this cohort. Those patients with poor outcome
      after MIOR were significantly older than those with good outcome (mean age: 64.6
      vs 51.4 years, P=0.006). In this study, a trend toward poor outcome was observed
      in cases with MIOR on internal carotid artery aneurysms (8/14, 57.1% vs 2/9,
      22.2% and 1/6, 16.7% on middle cerebral artery and anterior communicating artery
      aneurysms, P=0.197, after adjustment for age factor). There was a higher
      incidence of a poor outcome when MIOR occurred during clip application (5/6,
      83.3% vs 1/5, 20.0% and 5/19, 26.3% when MIOR happened during brain retraction
      and aneurysm dissection, P=0.041 after adjustment with the factor of age).
      CONCLUSION: Although a larger sample population is required for a more conclusive
      result, MIOR occuring in older age, during clip application, or on an internal
      carotid artery aneurysm possibly has the trend to bear a worse outcome in the
      cohort of patients with MIOR during aneurysm surgery.

PMID- 24030090
TI  - A reversible stroke-like splenial lesion in viral encephalopathy.
AB  - PURPOSE: An ovoid reversible lesion in the central portion of the splenium of the
      corpus callosum without any accompanying lesions in MRI was uncommon in patients
      with encephalitis. We aim to report a virus-related encephalitis patient
      presenting with a reversible isolated ovoid lesion in splenium, mimicking acute
      infarction. CASE REPORT: A 32 years old previously healthy man suffered from
      intermittent fever up to 39 degrees C accompanied with severe headache, drowsy
      consciousness, vomiting and diarrhea 2 days before admission. CSF study showed
      lymphocyte-predominant pleocytosis (lymphocyte/neutrophil 9/0), elevated level of
      protein (120mg/dL) but normal sugar level (42mg/dL). PCR for HSV-1/2, TB, and
      influenza antigen were negative. He was diagnosed as possibly virus-related
      encephalitis and receiving intravenous Acyclovir treatment. Brain MRI showed
      leptomeningeal enhancement. Notably, one 2.4cm-sized focal lesion with
      hyperintensity in diffusion weighted image (DWI) and hypointensity in apparent
      diffusion coefficient (ADC) was noted near the splenium of the corpus callosum,
      mimicking acute cerebral infarction. Intravenous Acyclovir was kept use and anti
      tuberculosis agent (Rifampicin, Isoniazid, Pyrazinamide, Ethambutol) were added.
      His consciousness gradually recovered 2 weeks after treatment and there was no
      any neurological sequel left. Follow-up MRI 2 months later was normal without any
      residual lesions. CONCLUSION: Our case confirmed with previous findings that a
      reversible stroke-like splenial lesion could be seen in virus related
      encephalopathy and regarded as a good prognosis marker. Transient intramyelinic
      edema or inflammatory infiltrate is the possible mechanism and further studies
      enrolling more related cases will be needed to confirm our finding.

PMID- 24030091
TI  - Intrasinus thrombolysis by mechanical and urokinase for severe cerebral venous
      sinus thrombosis : a case report.
AB  - PURPOSE: Cerebral venous and sinus thrombosis (CVST) is a rare stroke disorder,
      which requires prompt recognition and appropriate intervention to prevent a
      devastating outcome. Intrasinus thrombolysis is an alternative and effective
      method to anticoagulant therapy for the treatment of CVST, but is rarely used in
      Taiwan. CASE REPORT: A 46-year-old man presented with a one-week history of
      intractable headache and progressive weakness of his right lower limb. Magnetic
      resonance venography of the brain confirmed a diagnosis of extensive venous sinus
      thrombosis. The patient was successfully treated by direct intrasinus
      thrombolysis with urokinase. CONCLUSION: This case highlights the benefit of
      early intrasinus thrombolysis for the treatment of CVST.

PMID- 24030092
TI  - Bath-related thunderclap headache associated with subarachnoid and intracerebral
      hemorrhage.
AB  - PURPOSE: Bath-related thunderclap headache (BRTH) is a rare and usually benign
      condition. We report a case of episodic explosive thunderclap headache (TH)
      provoked by showering water, with the complications of cortical subarachnoid
      hemorrhages (SAH) and delayed intracerebral hemorrhage (ICH). CASE REPORT: A 56
      year-old premenopausal woman, without chronic illness or headache history,
      suffered from 4 episodes of severe explosive TH within 11 days. Two of these
      attacks were provoked by hot water and 1 by cold water. A small acute SAH was
      found in the left high frontal cortex on brain computed tomography (CT) performed
      7 days after the first attack (day 7). Brain magnetic resonance imaging (MRI) and
      angiography (MRA) on day 9 disclosed a new acute SAH in the right frontal cortex
      but with no apparent vasoconstriction. CT angiography (CTA) on day 12 first
      revealed vasoconstriction in the M2 segment of right middle cerebral artery
      (MCA), and found a new ICH in the right anterior frontal lobe. Conventional
      angiography on day 14 revealed partial remission of vasoconstriction with only
      mild short segmental narrowing at the proximal M1 segment of right MCA. The
      patient had no clinical neurological deficit. She was free of headache at day 11
      when she started taking nimodipine. CONCLUSION: Reversible cerebral
      vasoconstriction syndrome (RCVS) presented with BRTH is rare and is not always
      that benign as was once thought. The delayed ICH and the short-period of
      vasoconstriction in this patient extended our knowledge that the time course of
      the complications and the duration of vasospasm in RCVS could vary widely among
      patients. Nimodipine is probably effective in both relieving symptoms and
      reversing vasoconstriction.

PMID- 24030093
TI  - Epidermoid cyst presenting as isolated trigeminal neuralgia - two case reports.
AB  - PURPOSE: Symptomatic TN accounts for up to 15% of all TN. Though there are many
      established "red flag" signs, it is still sometimes difficult to sift symptomatic
      from classic TN. We herein report two cases of isolated TN with normal neurologic
      examinations and then tissue proved as epidermoid cyst. CASE REPORT:  CASE 1: A
      17-year-old girl presented with paroxysmal intense pain mixed dull background
      pain at right mandibular region for one month. The blink reflex demonstrated
      brainstem lesion and brain magnetic resonance imaging (MRI) revealed a huge
      lobulated tumor in right cerebellopontine angle (CPA) with obvious brainstem
      compression. Her right facial pain was nearly completely disappeared
      postoperatively. CASE 2: The 48-year-old woman had chronic paroxysmal electric
      like and burning pain in left V3 region for more than 5 years. Because of
      refractory pain, brain MRI was arranged and showed a non-enhancing cystic lesion
      at left CPA. Post operative complications occurred as left multiple lower cranial
      nerve palsies and Horner syndrome, and truncal ataxia. Her facial pain was
      completely free after 1 month follow up. CONCLUSION: In the first patient,
      teenage onset, abnormal trigeminal reflex, and early developing background pain
      struck us directly to symptomatic TN. In the second case, we suspected
      symptomatic TN with uncertainty before image study. TN could be the isolated
      initial symptom of CPA epidermoid cysts. In consideration about pretty high
      prevalence of symptomatic TN, physicians should be more alert and straightforward
      arrange neuroimage when facing TN patients with atypical presentation.

PMID- 24030094
TI  - Neurological manifestation in new emerging H7N9 influenza:an issue in neurology.
AB  - The emerging of new H7N9 influenza virus infection in February 2013 brings
      attention of world health scientists on its possibility to cause worldwide
      pandemic. The new H7N9 bird flu is a new disease manifesting with acute
      respiratory features plus additional atypical clinical manifestations. Of those
      atypical clinical features, neurological presentation is an interesting issue.
      This work presents the summary on evidence on neurological manifestation in new
      emerging H7N9 influenza.

PMID- 24030095
TI  - Embolism from external carotid artery and stroke.

PMID- 24030096
TI  - Central pontine myelinolysis in a chronic alcoholic patient with hyperglycemic
      hyperosmotic state.

PMID- 24030097
TI  - Time dependence of cisplatin-induced duplex dissociation of 15-mer RNAs and
      mature miR-146a.
AB  - The kinetics for the binding of cisplatin to duplex RNAs, two fully complementary
      model systems and mature miR-146a, exhibits a linear dependence on cisplatin
      concentration and results in duplex dissociation at 38  degrees C. 

PMID- 24030098
TI  - Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma:
      subset analysis of the NHL-003 study.
AB  - BACKGROUND: Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin
      lymphoma with poor overall prognosis, requiring the development of new therapies.
      Lenalidomide is an immunomodulatory agent demonstrating antitumor and
      antiproliferative effects in MCL. We report results from a long-term subset
      analysis of 57 patients with relapsed/refractory MCL from the NHL-003 phase II
      multicenter study of single-agent lenalidomide in patients with aggressive
      lymphoma DESIGN: Lenalidomide was administered orally 25 mg daily on days 1-21
      every 28 days until progressive disease (PD) or intolerability. The primary end
      point was overall response rate (ORR). RESULTS: Fifty-seven patients with
      relapsed/refractory, advanced-stage MCL had a median of three prior therapies.
      The ORR was 35% [complete response (CR)/CR unconfirmed (CRu) 12%], with a median
      duration of response (DOR) of 16.3 months (not yet reached in patients with
      CR/CRu) by blinded independent central review. The median time to first response
      was 1.9 months. Median progression-free survival was 8.8 months, and overall
      survival had not yet been reached. The most common grade 3/4 adverse events (AEs)
      were neutropenia (46%), thrombocytopenia (30%), and anemia (13%). CONCLUSIONS:
      These results show the activity of lenalidomide in heavily pretreated,
      relapsed/refractory MCL. Responders had a durable response with manageable side
      effects. Clinical trial number posted on www.clinicaltrials.gov NCT00413036.

PMID- 24030099
TI  - Unraveling sterol-dependent membrane phenotypes by analysis of protein abundance
      ratio distributions in different membrane fractions under biochemical and
      endogenous sterol depletion.
AB  - During the last decade, research on plasma membrane focused increasingly on the
      analysis of so-called microdomains. It has been shown that function of many
      membrane-associated proteins involved in signaling and transport depends on their
      conditional segregation within sterol-enriched membrane domains. High throughput
      proteomic analysis of sterol-protein interactions are often based on analyzing
      detergent resistant membrane fraction enriched in sterols and associated
      proteins, which also contain proteins from these microdomain structures. Most
      studies so far focused exclusively on the characterization of detergent resistant
      membrane protein composition and abundances. This approach has received some
      criticism because of its unspecificity and many co-purifying proteins. In this
      study, by a label-free quantitation approach, we extended the characterization of
      membrane microdomains by particularly studying distributions of each protein
      between detergent resistant membrane and detergent-soluble fractions (DSF). This
      approach allows a more stringent definition of dynamic processes between
      different membrane phases and provides a means of identification of co-purifying
      proteins. We developed a random sampling algorithm, called Unicorn, allowing for
      robust statistical testing of alterations in the protein distribution ratios of
      the two different fractions. Unicorn was validated on proteomic data from methyl
      beta-cyclodextrin treated plasma membranes and the sterol biosynthesis mutant
      smt1. Both, chemical treatment and sterol-biosynthesis mutation affected similar
      protein classes in their membrane phase distribution and particularly proteins
      with signaling and transport functions. 

PMID- 24030100
TI  - Phosphatase of regenerating liver 3 (PRL3) provokes a tyrosine phosphoproteome to
      drive prometastatic signal transduction.
AB  - Phosphatase of regenerating liver 3 (PRL3) is suspected to be a causative factor
      toward cellular metastasis when in excess. To date, the molecular basis for PRL3
      function remains an enigma, making efforts at distilling a concerted mechanism
      for PRL3-mediated metastatic dissemination very difficult. We previously
      discovered that PRL3 expressing cells exhibit a pronounced increase in protein
      tyrosine phosphorylation. Here we take an unbiased mass spectrometry-based
      approach toward identifying the phosphoproteins exhibiting enhanced levels of
      tyrosine phosphorylation with a goal to define the "PRL3-mediated signaling
      network." Phosphoproteomic data support intracellular activation of an extensive
      signaling network normally governed by extracellular ligand-activated
      transmembrane growth factor, cytokine, and integrin receptors in the PRL3 cells.
      Additionally, data implicate the Src tyrosine kinase as the major intracellular
      kinase responsible for "hijacking" this network and provide strong evidence that
      aberrant Src activation is a major consequence of PRL3 overexpression.
      Importantly, the data support a PDGF(alpha/beta)-, Eph (A2/B3/B4)-, and Integrin
      (beta1/beta5)-receptor array as being the predominant network coordinator in the
      PRL3 cells, corroborating a PRL3-induced mesenchymal-state. Within this network,
      we find that tyrosine phosphorylation is increased on a multitude of signaling
      effectors responsible for Rho-family GTPase, PI3K-Akt, STAT, and ERK activation,
      linking observations made by the field as a whole under Src as a primary signal
      transducer. Our phosphoproteomic data paint the most comprehensive picture to
      date of how PRL3 drives prometastatic molecular events through Src activation. 

PMID- 24030102
TI  - Laboratory coagulation parameters in extremely premature infants born earlier
      than 27 gestational weeks upon admission to a neonatal intensive care unit.
AB  - BACKGROUND: Few published data exist to guide interpretation of coagulation times
      in extremely premature infants. OBJECTIVE: To determine coagulation reference
      ranges on day 1 of life in extremely premature infants. METHODS: A retrospective
      review of day 1 coagulation tests was performed in 144 infants <27 weeks'
      gestation between 2004 and 2010 in a tertiary neonatal unit. Samples were drawn
      through a non-heparinized umbilical or peripheral venous catheter as part of
      routine clinical care. RESULTS: Mean (SD) and median (range) prothrombin times
      (PT) of 21.5 (5.3) and 20.2 (13.3-39) s, respectively, activated partial
      thromboplastin times (APTT) of 75.2 (27.8) and 67.4 (34.9-191.6) s, respectively,
      and plasma fibrinogen levels of 1.9 (1.1) and 1.4 (0.5-4.8) g/l, respectively,
      were reported. Using reference intervals derived from the 2.5th to 97.5th
      centiles, ranges of 14.4-36.7 s, 40.5-158.5 s and 0.7-4.8 g/l were determined for
      PT, APTT and plasma fibrinogen levels, respectively. In a subcohort with grade 0
      2 intraventricular haemorrhage (n = 92), mean PT and APTT were 20.9 and 71.3 s,
      respectively, versus mean PT and APTT of 23.1 and 88.4 s (p = 0.06 and p = 0.03),
      respectively for those with grade 3-4 intraventricular haemorrhage. Mean PT and
      APTT in a cohort of infants defined to be small for gestational age were 22 and
      76.8 s. These results did not differ significantly from non-small for gestational
      age infants, with a mean PT and APTT of 19.5 and 73.4 s (p = 0.09 and p = 0.7).
      CONCLUSIONS: Reference ranges based on retrospective data were determined for PT,
      APTT and fibrinogen in a large cohort of extremely preterm infants.

PMID- 24030103
TI  - Knowledge, attitudes and practices of traceability among livestock traders in
      south-western Nigeria: implications for sustainable livestock industry.
AB  - Livestock diseases and other animal health events are a threat to achieving
      sustainable livestock industry. The knowledge of trace-back and the practice of
      providing feedback on diseases encountered in slaughtered animals from the
      abattoir to the farm can help limit the spread as well as manage potential future
      incidents of such diseases. We assessed the knowledge, attitudes and practices of
      200 willing livestock traders on traceability in Bodija Municipal Abattoir, south
      western Nigeria. The results reveal that the majority of these traders had poor
      knowledge (79.5 %) and practices (74.0 %) of traceability, though 89.5 %
      demonstrated good attitudes. While 22.9 % knew that traceability could be an
      effective means to control diseases, only a lower proportion (9.0 %) knew the
      health status of the animals being purchased. Though 29.0 % reported the diseases
      encountered in their animals during slaughter to the farm, only 9.5 % followed up
      to ensure the farmers take steps at preventing further occurrence of the reported
      diseases. While age (p = 0.000; 0.014) and education (p = 0.000; 0.000) were both
      significant for good knowledge and attitudes, frequency of condemned cases (p =
      0.000) and length of years in the trade (p = 0.004) were, respectively,
      significant for good knowledge and attitudes with none associated with practice.
      These poor levels of knowledge and practices of traceability are a threat to
      sustainable livestock industry, food security and human health; hence, there is
      an urgent need to institute national feedback mechanism on slaughtered animals in
      order to strengthen interventions against diseases at farm levels. 

PMID- 24030104
TI  - Values for contemporary nursing practice: waving or drowning?

PMID- 24030101
TI  - Quantitative proteomic and functional analysis of liver mitochondria from high
      fat diet (HFD) diabetic mice.
AB  - Insulin resistance plays a major role in the development of type 2 diabetes and
      obesity and affects a number of biological processes such as mitochondrial
      biogenesis. Though mitochondrial dysfunction has been linked to the development
      of insulin resistance and pathogenesis of type 2 diabetes, the precise mechanism
      linking the two is not well understood. We used high fat diet (HFD)-induced
      obesity dependent diabetes mouse models to gain insight into the potential
      pathways altered with metabolic disease, and carried out quantitative proteomic
      analysis of liver mitochondria. As previously reported, proteins involved in
      fatty acid oxidation, branched chain amino acid degradation, tricarboxylic acid
      cycle, and oxidative phosphorylation were uniformly up-regulated in the liver of
      HFD fed mice compared with that of normal diet. Further, our studies revealed
      that retinol metabolism is distinctly down-regulated and the mitochondrial
      structural proteins-components of mitochondrial inter-membrane space bridging
      (MIB) complex (Mitofilin, Sam50, and ChChd3), and Tim proteins-essential for
      protein import, are significantly up-regulated in HFD fed mice. Structural and
      functional studies on HFD and normal diet liver mitochondria revealed remodeling
      of HFD mitochondria to a more condensed form with increased respiratory capacity
      and higher ATP levels compared with normal diet mitochondria. Thus, it is likely
      that the structural remodeling is essential to accommodate the increased protein
      content in presence of HFD: the mechanism could be through the MIB complex
      promoting contact site and crista junction formation and in turn facilitating the
      lipid and protein uptake. 

PMID- 24030105
TI  - Forced genital cutting in North America: feminist theory and nursing
      considerations.
AB  - This article will examine forced nontherapeutic genital cutting (FNGC) through
      the lens of feminist theory and in relation to the concept of social justice in
      nursing. I will address the underlying assumptions of feminism and how they apply
      to the two currently legal forms of FNGC in North America: male infant
      circumcision and intersex infant/child genital cutting. Through a literature
      review and critical analysis of these practices, I will illustrate the challenges
      they present when considering the role of nurses in promoting social justice. If
      feminism asserts that bodily integrity, autonomy, and fundamental human rights
      are essential components of gender equality, it follows that these must be
      afforded to all genders without discrimination. Historically, there have been few
      feminists who have made this connection, yet a growing and diverse movement of
      people is challenging the frameworks in which we consider genital cutting in our
      society. Nurses are positioned well to be at the forefront of this cause and have
      a clear ethical duty to advocate for the elimination of all forms of FNGC.

PMID- 24030107
TI  - Systematic review of prevention and management strategies for the consequences of
      gender-based violence in refugee settings.
AB  - Uncertainties continue regarding effective strategies to prevent and address the
      consequences of gender-based violence (GBV) among refugees. The databases of
      PubMed, Cochrane Library, Scopus, PsycINFO, Web of Science, Anthropology Plus,
      EMBASE, DARE, Google Scholar, MSF Field Research, UNHCR and the regional and
      global indices of the WHO Global Health Library were searched twice within a 6
      month period (April and September 2011) for English-language clinical, public
      health, basic and social science studies evaluating strategies to prevent and
      manage health sequelae of GBV among refugees before September 2011. Studies not
      primarily about prevention and treatment, and not describing population, health
      outcome and interventions, were excluded. The literature search for the
      prevention and management arms produced 1212 and 1106 results, respectively.
      After reviewing the titles and abstracts, 29 and 27 articles were selected for
      review in their entirety, none of which met the inclusion criteria. Multiple
      panels of expert recommendations and guidelines were not supported by primary
      data on actual displaced populations. There is a dire need for research that
      evaluates the efficacy and effectiveness of various responses to GBV to
      ultimately allow a transition from largely theoretical and expertise driven to a
      more evidence-based field. We recommend strategies to improve data collection and
      to overcome barriers in primary data driven research.

PMID- 24030108
TI  - Critical care medicine in Nepal: where are we?
AB  - Although critical care medicine has been established as a separate specialty in
      the rest of the world it is still in its initial stages of development in Nepal
      and intensive care units (ICUs) here are still in primitive stages. This article
      describes the history, the types and current status of ICUs, the challenges, and
      academic training and certification in critical care medicine in Nepal, compared
      with existing ICUs in other parts of the world.

PMID- 24030109
TI  - Strategies to increase facility-based skilled birth attendance in South Asia: a
      literature review.
AB  - Global strategies to target high maternal mortality ratios are focused on
      providing skilled attendance at delivery as well as access to emergency obstetric
      care. South Asia has the lowest rates of skilled birth attendance in the world,
      and Nepal is lagging behind neighbouring countries. This review looks at the
      demand-side barriers to seeking care as well as strategies to increase facility
      delivery in rural South Asia. A search was made of key databases, including
      PubMed and the WHO, for literature relating to utilisation of facility delivery
      in South Asia. The main factors found to influence facility delivery in South
      Asia were physical and financial barriers, socioeconomic and educational status,
      obstetric history and awareness of danger signs, sociocultural factors and
      perceived quality of care. Strategies to increase facility delivery include
      maternity waiting homes, demand-side financing schemes, education programmes and
      participatory women's groups. Increasing utilisation of delivery services in
      South Asia requires a multisectoral approach. Key areas are increasing education
      for girls as well as empowering women through women's groups and community
      mobilisation. Removal of user fees appears to be successful but needs to be
      sustainable and equitable in its delivery.

PMID- 24030110
TI  - Two years post-tsunami in Thailand: who still needs assistance?
AB  - BACKGROUND: On 26 December 2004, 280 000 people lost their lives in the Asia
      Pacific region. A massive earthquake struck Indonesia, triggering a tsunami that
      affected several countries, including Thailand. This tsunami had important
      implications for the health status of Thai citizens and health planning, and thus
      there is a need to study its long-term impact. METHODS: This cohort study
      identified determinants of health service utilization (outpatient services,
      inpatient services, home care, medications and informal care) 1 and 2 years post
      tsunami in Thailand. A two-part model with a multivariate logistic regression for
      each part was used to identify determinants of the propensity and intensity of
      utilization. RESULTS: Of 1943 participants, 1889 (97.2%) participated at 1 year
      and 1814/1889 (96.0%) at 2 years. Common determinants of health service
      utilization in post-tsunami settings were age, marital status, education level,
      employment status, number of health conditions and (physical and mental) health
      status. CONCLUSIONS: Knowing the determinants of health service use, health
      providers may be able to establish programmes for, or to carefully monitor
      populations, who are more likely to use services. The study results may be used
      to inform requests for health resources or to assist the development of
      guidelines for long-term disaster recovery planning.

PMID- 24030111
TI  - Community-based survey of podoconiosis in Bedele Zuria woreda, west Ethiopia.
AB  - BACKGROUND: Podoconiosis is a neglected tropical disease resulting in progressive
      bilateral swelling of the lower legs in barefoot individuals exposed to red-clay
      soil derived from volcanic rocks. It is a considerable public health problem in
      countries across tropical Africa, Central America and northern India. The present
      study aimed to assess the prevalence and clinical features of podoconiosis, and
      patients' experience of disease prevention and treatment, in Bedele Zuria woreda
      (district), west Ethiopia. METHODS: The study was conducted during 2011 and
      involved a house-to-house survey in all 2285 households of five randomly selected
      rural kebeles (villages). RESULTS: The prevalence of podoconiosis was 5.6%
      (379/6710) (95% CI 5.1-6.2%) and was significantly greater among women than men
      (6.6% vs 4.7%; p = 0.001). A total of 311 (16.9%) households had at least one
      member with podoconiosis, and 128 (33.8%) study participants reported having a
      blood relative with podoconiosis. Two hundred and forty-three (76.4%)
      podoconiosis patients were in the economically productive age group of 15-64
      years. On average, a patient experienced at least six episodes of
      adenolymphangitis per year resulting in a loss of 25 working days per year.
      CONCLUSION: This study has revealed a high burden of podoconiosis in west
      Ethiopia, and suggests that disease prevention and treatment programmes are
      needed.

PMID- 24030112
TI  - Systemic constraints continue to limit coverage of intermittent preventive
      treatment for malaria in pregnancy in southeast Tanzania.
AB  - BACKGROUND: Factors limiting coverage of intermittent preventive treatment for
      malaria in pregnancy (IPTp) in Tanzania were explored from the perspective of
      health workers, in order to make recommendations to improve service delivery.
      Recent data estimates coverage of the recommended two doses of IPTp at 26.3%, far
      short of the national target of 80%. METHODS: Semistructured interviews were
      conducted with 13 health workers and 2 health managers during June 2011 in
      Ikwiriri, southeast Tanzania. RESULTS: Delivery of sulfadoxine-pyrimethamine (SP)
      was severely constrained by drug shortages and widespread stock-outs, indicative
      of ongoing difficulties in the wider health system. While SP was well known and
      attitudes towards IPTp were positive, health workers were often not informed of
      up-to-date dosing schedules, limiting coverage. Recent literature suggests this
      could be due to inconsistent and conflicting national guidelines. In addition, it
      was found that two pills, instead of the recommended three pills, per dose of
      IPTp were frequently given to pregnant women, a finding previously unreported.
      CONCLUSION: To maximize IPTp coverage, sufficient and consistent supplies of SP
      to both public and private health facilities are a necessity, combined with
      effective communication of revised dosing schedules. Further research is
      warranted to investigate the aberrant administration of two pills per dose, as it
      may exacerbate drug resistance.

PMID- 24030113
TI  - Comparing the effectiveness of efavirenz and nevirapine for first-line
      antiretroviral therapy in a South African multicentre cohort.
AB  - INTRODUCTION: Current WHO guidelines for developing countries recommend efavirenz
      (EFV) and nevirapine (NVP) for first-line antiretroviral treatment (ART). This
      paper compares the effectiveness of EFV and NVP among ART-naive patients
      initiating treatment at 56 public health facilities in South Africa between
      January 2004 and December 2007. METHODS: Participants were assigned to the EFV or
      NVP cohorts depending on their baseline ART regimen. Mortality, viral load
      suppression after 6 months and ART regimen change were compared between the
      cohorts using Cox proportional hazards models and logistic regression. RESULTS:
      At initiation, 19 441 (71.1%) patients started EFV and 7909 (28.9%) started NVP
      treatment. The median follow-up period was 9.5 months (IQR 4.6-17.7). After
      adjustment, mortality was similar in the two cohorts, (adjusted HR = 1.07, 95% CI
      0.89-1.28). Viral load suppression at 6 months was higher in the EFV cohort
      overall (adjusted odds ratio [AOR] = 1.29, 95% CI 1.05-1.59) and in women aged 16
      40 years (AOR = 1.35, 95% CI 1.11-1.63) and women with CD4 counts <25 cells/uL
      (AOR = 1.95, 95% CI 1.01-3.76). Patients starting on EFV were 47% less likely to
      change regimen (AOR = 0.53, 95% CI 0.48-0.59). DISCUSSION: These findings suggest
      the superior effectiveness of EFV for first-line ART compared with NVP and should
      be considered during development of future ART guidelines for high-burden
      regions.

PMID- 24030114
TI  - Timeliness and completeness of vaccination and risk factors for low and late
      vaccine uptake in young children living in rural southern Tanzania.
AB  - BACKGROUND: We studied coverage and timeliness of vaccination and risk factors
      for low and delayed vaccine uptake in children aged <2 years in rural Tanzania.
      METHODS: We used data from a cluster survey conducted in 2004, which included
      1403 children. Risk factors were analysed by log-binomial regression adjusted for
      the clustering. The analysis was restricted to BCG, first and third dose of
      Diphtheria-Tetanus-Pertussis vaccines (DTP-1 and DTP-3) and first dose of measles
      containing vaccine (MCV-1). RESULTS: Coverage for BCG, DTP-1, DTP-3 and MCV-1 was
      94%, 96%, 90% and 86%, respectively. Delayed vaccination (>1 month after the
      recommended age) occurred in 398/1205 (33%) children for BCG, 404/1189 (34%) for
      DTP-1, 683/990 (69%) for DTP-3 and 296/643 (46%) for MCV-1. Coverage was lower
      for all vaccines except DTP-1 in children living >=5 km from a healthcare
      facility. Delayed uptake was associated with poverty. Low and delayed MCV-1
      vaccination was associated with low maternal education. Delayed BCG vaccination
      was associated with ethnicity and rainy season. CONCLUSION: Despite reasonably
      high vaccination coverage, we observed substantial vaccination delays,
      particularly for DTP-3 and MCV-1. We found specific factors associated with low
      and/or delayed vaccine uptake. These findings can help to improve strategies to
      reach children who remain inadequately protected.

PMID- 24030115
TI  - Assessment of the adherence of community health workers to dosing and referral
      guidelines for the management of fever in children under 5 years: a study in
      Dangme West District, Ghana.
AB  - BACKGROUND: Community health workers (CHW) manage simple childhood illnesses in
      many developing countries. Information on CHWs' referral practices is limited. As
      part of a large cluster-randomised trial, this study assessed CHWs' adherence to
      dosing and referral guidelines. METHODS: Records of consultations of children
      aged 2-59 months with fever managed by CHWs were analysed. Appropriate use of
      drugs was defined as provision of the correct drug pack(s) for the child's age
      group. Symptoms requiring referral were categorised into danger signs,
      respiratory distress and symptoms indicating other illnesses. Multivariate
      logistic regression examined symptoms most likely to be noted as requiring
      referral and those associated with provision of a written referral. RESULTS: Most
      children (11 659/12 330; 94.6%) received the appropriate drug. Only 161 of 1758
      (9.2%) children who, according to the guidelines required referral were provided
      with a written referral. Not drinking/breastfeeding, persistent vomiting,
      unconsciousness/lethargy, difficultly breathing, fast breathing, bloody stool,
      sunken eyes and pallor were symptoms significantly associated with being
      identified by CHWs as needing referral or receiving a written referral.
      CONCLUSIONS: CHWs' adherence to dosing guidelines was high. Adherence to referral
      guidelines was inadequate. More effort needs to be put into strengthening
      referral practices of CHWs within comparable community programmes.

PMID- 24030116
TI  - Dipstick urinalysis for diabetes screening in TB patients.
AB  - INTRODUCTION: Diabetes knowledge among TB patients can contribute to improved TB
      treatment outcomes, but lack of diabetes diagnosis awareness is a limitation in
      developing countries. Given its low cost, the sensitivity of urine glucose
      dipsticks for diabetes screening in TB patients was assessed. METHODS: Glycosuria
      was assessed in 90 newly diagnosed TB patients (38 with diabetes) in south Texas,
      USA (n = 20) and northeast Mexico (n = 70) during January 2009-December 2010.
      RESULTS: Glycosuria was detected in 65% of the diabetic patients with chronic
      hyperglycemia (positive predictive value 91%, negative predictive value 84%).
      CONCLUSION: We propose that TB clinics with limited budgets where portable
      glucometers may not be available conduct universal screening for diabetes with
      urine dipsticks. This could be followed by blood glucose or HbA1c testing in the
      subset of patients requiring confirmation or higher sensitivity assessment, to
      improve the comanagement of TB and diabetes.

PMID- 24030117
TI  - Management of disseminated intravascular coagulopathy with direct factor Xa
      inhibitor rivaroxaban in Klippel-Trenaunay syndrome.
AB  - Klippel-Trenaunay syndrome (KTS) is a rare congenital anomaly characterized by
      malformation of lymph and blood vessels as well as growth disturbance of soft
      tissue and bone. The clinical picture is variable and associated with an
      increased risk of thromboembolic events mediated by intravascular coagulopathy in
      venous malformations. Here, we report on a male patient with KTS suffering from
      recurrent deep vein thrombosis (DVT) and life-threatening bleeding due to
      consumptive coagulopathy. Furthermore, we describe the successful long-term
      anticoagulant management with rivaroxaban. 

PMID- 24030118
TI  - Increased PAC-1 expression among patients with multiple myeloma on concurrent
      thalidomide and warfarin.
AB  - Treatment with thalidomide is associated with vascular thrombosis. The effect of
      thalidomide on platelet activation is unclear, although the use of aspirin is
      justified for thromboprophylaxis. A study on platelet activation markers was done
      among multiple myeloma patients receiving thalidomide therapy with warfarin as
      thromboprophylaxis. Strict criteria and procedure were set to avoid
      misinterpretation of platelet activation other than due to the thalidomide's
      effect. Blood specimen pre and post thalidomide therapy were used for flow
      cytometric analysis. Platelet surface P-selectin, CD62P expression and PAC-1
      (antibody that recognizes conformational change of the GPIIb/IIIa complex) were
      examined by using three-colour flowcytometer. Increased expression marker for PAC
      1 was observed after 4 weeks of thalidomide treatment (P < 0.05) indicating one
      aspect of platelet activation activity seen in these patients. The mechanism of
      thrombosis by thalidomide is probably multifactorial and one of them is likely
      through platelet activation. Further study on the affected pathway/s in the
      platelet activation process would confirm the exact mechanism of thalidomide
      induced thrombosis and potential extended usage of this drug in future. 

PMID- 24030119
TI  - The clinical utility of fibrin-related biomarkers in sepsis.
AB  - Sepsis is associated with systemic inflammatory responses and induction of
      intravascular fibrin formation. Our aim is to investigate whether three fibrin
      related markers (FRM) reflect the extent of coagulation activation in vivo and
      evaluate their clinical usefulness in identifying as well as monitoring patients
      with sepsis. Fibrin-degradation products (FDP), D-dimer and soluble fibrin
      monomer assays were measured on plasma samples from patients in the ICU with
      sepsis (n = 37), systemic inflammatory response syndrome (SIRS) (n = 35) and
      healthy individuals (n = 15). The levels were correlated with each other and also
      with fibrinogen, prothrombin time, platelets and antithrombin III. Clinical
      correlation was also performed for the diagnosis of sepsis and longitudinal
      monitoring for survival or death.There was strong correlation between the three
      FRM (r = 0.38-0.93, P < 0.0001) with only fibrin monomer correlating
      significantly with prothrombin time, fibrinogen and platelet levels. Clinically,
      all three FRM could discriminate between patients with sepsis, SIRS and healthy
      individuals with FDP, and D-dimer showing statistical significance (P < 0.05). No
      FRM predicted outcome from a single measurement but FDP was significantly able to
      predict patient survival from serial samples [mean FDP (MUg/ml) from 35.36 to
      21.37 (first to third ICU-day), P < 0.05]. Fibrin monomer appears the most
      sensitive indicator of coagulation activation, whereas D-dimer and FDP levels can
      significantly differentiate ICU patients with sepsis from those without. In
      addition, FDP would be preferable for monitoring with its statistically
      significant time-dependent prediction of survival or death from sepsis. 

PMID- 24030120
TI  - Risk factors for thrombosis in Serbian children.
AB  - Venous and arterial thromboses are increasingly encountered in the pediatric
      population. We present results of a case-control study of inherited and acquired
      risk factors for thrombosis in 129 pediatric patients from the first day of life
      to 18 years. The aims of study were to determine the importance of thrombophilic
      risk factors and comorbidity as a cause of thrombosis in children. Single
      thrombophilic risk factor was found in 24.4% (n = 21), whereas combined
      thrombophilic factors were found in 15.1% (n = 13) patients. A total of 87.2% of
      the children had recognized thrombophilic risk factors for thrombosis and/or
      additional comorbid risk factors. The single independent risk factors for
      thrombosis were mutation of factor V Leiden (P = 0.021), lupus anticoagulant
      antibodies (P = 0.028), and comorbidity (P = 0.000). Mutation of factor V Leiden
      [odds ratio (OR), 6.2 (95% confidence interval, CI 1.1-38.1, P = 0.048] was found
      to be a risk factor for venous thrombosis. Lupus anticoagulant antibodies were
      related to both venous (P = 0.008) and arterial thrombosis (P = 0.016). The
      frequency of inherited thrombophilic factors were the same in neonates and
      adolescents (23%). The prothrombotic gene mutations were present in 18.6% (n = 8)
      of asymptomatic children. Our study confirms that thrombosis in children is a
      multifactorial disorder, and associated most with the underlying medical disease
      (comorbidity) for vein thrombosis [OR, 18.6 (95% CI 3.7-93.4), P = 0.000] and for
      arterial thrombosis [OR, 10.5 (95% CI 2.2-49.9) P = 0.003]. Inherited
      thrombophilic disorders contributed to the development of thrombosis in children.

PMID- 24030121
TI  - Platelet cytoskeleton and its hemostatic role.
AB  - Upon vascular injury, platelets adhere to the exposed extracellular matrix, which
      triggers the platelet activation and aggregation to form a hemostatic plug to
      seal the wound. All of these events involve dramatic changes in shape because of
      the cytoskeleton reorganization. The versatility of the cytoskeleton's main
      elements depends on the biochemical nature of the elements, as well as on the
      associated proteins that confer multiple functions within the cell. The list of
      these associated proteins grows actively, increasing our knowledge concerning the
      complexity of platelet cytoskeleton machinery. The present review evidences the
      recently described platelet proteins that promote characteristic modifications in
      their cytoskeleton organization, with special focus on the dystrophin
      glycoprotein complex. 

PMID- 24030123
TI  - Patients' intentions to seek medication information from pharmacists.
AB  - OBJECTIVES: To determine whether perceived medication use knowledge held and/or
      needed influenced intention to seek information from pharmacists, whether an
      information-intention relationship held after accounting for other variables, and
      whether asking medication use knowledge questions increased pharmacist
      information-seeking intention. DESIGN: Cross-sectional study. SETTING United
      States during July 2012. PARTICIPANTS: Qualtrics national panel members 21 years
      or older obtaining a new chronic medication within previous 30 days.
      INTERVENTION: Internet-administered survey. MAIN OUTCOME MEASURES: Medication
      information-seeking intention, medication knowledge held and needed, and
      pharmacist medication information-seeking intention. RESULTS: Although knowledge
      held and needed were initially significant, they became nonsignificant after
      adding affective and evaluative attitudes, perceived control, and risk. The final
      best-fitting model explained 21% of variance in pharmacist information-seeking
      intention. Patient intentions to seek information from pharmacists increased
      significantly after being asked medication use knowledge questions. CONCLUSION:
      Perceptions of medication risk, attitudes, and information-seeking control
      predict pharmacist information-seeking intention and offer pharmacists an
      opportunity to market information services.

PMID- 24030124
TI  - Perceptions of the incorporation of health literacy in pharmacy training
      programs.
AB  - OBJECTIVES: To assess pharmacy residents' perceptions regarding the incorporation
      of health literacy in pharmacy school and pharmacy residency training and to
      assess confidence while interacting with patients of limited health literacy.
      DESIGN: Prospective cross-sectional study. SETTING: United States from March to
      May 2012. PARTICIPANTS: Postgraduate year (PGY)1 and -2 pharmacy residents and
      pharmacy residency program directors. INTERVENTION: Online survey. MAIN OUTCOME
      MEASURE: PGY1 and -2 resident perceptions of health literacy incorporation into
      pharmacy school and residency training. RESULTS: 939 surveys were completed.
      Residents agreed that their pharmacy school training encouraged the development
      of health literacy skills ( P < 0.001) and made efforts to improve health
      literacy awareness ( P < 0.001) significantly more than their PGY1 programs. In
      addition, they felt significantly more confident in their ability to communicate
      with patients with limited health literacy after their pharmacy school training
      compared with during or following PGY1 residency training ( P < 0.001); however,
      no difference was found regarding confidence in identifying patients of limited
      health literacy. CONCLUSION: PGY1 residency programs lag behind the efforts of
      schools of pharmacy to incorporate the health literacy training essential to
      encountering patients of limited health literacy. Future studies should assess
      whether these perceptions reflect true health literacy awareness and management
      among pharmacy residents.

PMID- 24030125
TI  - Factors affecting Medicare Part D beneficiaries' decision to receive
      comprehensive medication reviews.
AB  - OBJECTIVES: To identify factors influencing Medicare Part D beneficiaries'
      decision to receive pharmacist-provided comprehensive medication reviews (CMRs)
      and to evaluate their experiences with pharmacist-provided CMRs. DESIGN: Cross
      sectional descriptive study. SETTING: Beneficiaries living in Maryland or
      Minnesota, from November 2011 to January 2012. PARTICIPANTS: Medicare
      beneficiaries of two Medicare Part D plans who had completed a previous telephone
      interview for a larger project of medication therapy management quality
      improvement. INTERVENTION: Self-reported mail survey. MAIN OUTCOME MEASURES:
      Responses to survey items assessing beneficiaries' perceived importance of
      proposed factors affecting their decision to receive CMRs and items evaluating
      patients' experiences with pharmacist-provided CMRs if they had one in the
      previous year. RESULTS: The valid response rate was 33.4% (238 of 713). Among the
      proposed factors, "knowing the out-of-pocket cost" (4.12 +/- 1.28 [mean +/- SD])
      and "conducting in the usual pharmacy" (4.01 +/- 1.37) were most important in
      making a decision to get a CMR. Factors rated significantly more important by
      those who had versus had not received a CMR included "usual pharmacy," "receiving
      medication list," "physician's support," and "pharmacists discuss changes with
      physicians." About one-third (30.6%) of respondents reported having pharmacist
      provided CMRs within the previous year. Most respondents believed that having
      CMRs was important for their health (90.6%) and were satisfied with the results
      of CMRs (94.7%). CONCLUSION: Patients preferred their usual pharmacy or
      convenient places to have a CMR. Also, a collaborative pharmacist-physician
      working relationship would be helpful in providing CMRs. Patients who received
      CMRs expressed a positive attitude toward and satisfaction with pharmacist
      provided services.

PMID- 24030126
TI  - Parents' perceptions of pharmacists as providers of influenza vaccine to
      children.
AB  - OBJECTIVE: To examine parents' experience with the process of obtaining the
      influenza vaccine and their perceptions about pharmacists providing influenza
      vaccination services to their children. DESIGN: Cross-sectional descriptive
      study. SETTING: Wisconsin between November 2011 and April 2012. PARTICIPANTS:
      Children receiving an influenza vaccination from a Unity Health Insurance (UHI)
      covered pharmacy between September and December 2011 were identified from
      pharmacy claims data, and parents of the children were sent a letter requesting
      their participation in the study. INTERVENTION: Online survey. MAIN OUTCOME
      MEASURES: Parents' experience with the process of obtaining the influenza vaccine
      and their perceptions about pharmacists providing influenza vaccinations to their
      children. RESULTS: 179 parents received a letter from UHI requesting their
      participation in the study, and the usable response rate for the study was 48%.
      Parents' experience with the process of obtaining the influenza vaccine was
      positive. A majority of parents did not need an appointment (98%) and visited a
      pharmacy during the hours of 3:05 pm to 6:00 pm (51%). Approximately 97% of the
      responding parents felt confident about the pharmacist providing influenza
      vaccinations to their children. CONCLUSION: Parents appear to be willing to
      accept pharmacists as an immunization resource for their children.

PMID- 24030127
TI  - Evaluation of anticholinergic burden of medications in older adults.
AB  - OBJECTIVES: To calculate and describe the anticholinergic burden of medications
      in community-dwelling older adults and to identify patient-specific risk factors.
      DESIGN: Descriptive cross-sectional study. SETTING: Cardinal Health Visiting
      Pharmacist Program, Columbus, OH, between August 2002 and August 2009.
      PARTICIPANTS: Community-dwelling adults 65 years or older who were referred
      through LifeCare Alliance (a provider of home-based senior services).
      INTERVENTION: Comprehensive medication review records from medication therapy
      management (MTM) activities were used to calculate the anticholinergic burden
      using the anticholinergic cognitive burden (ACB) scale for each patient. MAIN
      OUTCOME MEASURE: Proportion of older adults in the community with a clinically
      relevant anticholinergic burden (defined as ACB score >=3). RESULTS: From 341
      included records, ACB score was calculated for all patients and an ACB score of 3
      or greater was identified in 47.8% (n = 163) of patients. The odds increased
      significantly as the number of prescription (odds ratio 1.23 [95% CI 1.14-1.32],
      P < 0.001] and over-the-counter (1.17 [1.02-1.33], P = 0.02] medications
      increased. The odds also were significantly greater for patients with
      hypertension (3.01 [1.73-5.21], P < 0.001) and depression (2.6 [1.14-5.9], P =
      0.02). CONCLUSION: Nearly one-half of community-dwelling older adults had a
      clinically relevant ACB score of 3 or greater. The ACB score could be used as a
      component of MTM services in a variety of practice settings to identify older
      adults who are at higher risk for potential central and peripheral adverse
      effects related to cumulative anticholinergic activity of their medications.
      Additional research to measure the clinical impact of ACB assessment and
      modification is needed.

PMID- 24030128
TI  - Outcomes of a pharmacist-managed medication refill program.
AB  - OBJECTIVE: To compare the completeness of medication and blood pressure
      monitoring among patients requesting medication refills through the pharmacist
      managed medication refill and laboratory monitoring program (MRLMP) versus usual
      care. DESIGN: Quasiexperimental study. SETTING: Kaiser Permanente Colorado
      between November 2011 and June 2012. PATIENTS: Patients requesting chronic
      medication prescription refills. INTERVENTION: Community pharmacists managed the
      refill authorization request (RAR) process at the intervention site. For each
      RAR, the pharmacist reviewed patient medication monitoring needs and ordered
      laboratory test(s) or a clinic visit, as needed, before approval. MAIN OUTCOME
      MEASURES: For medications due for laboratory or blood pressure monitoring at the
      time of the RAR, the 1-month rate of attaining complete monitoring was compared
      between groups. Pharmacist, primary care physician (PCP), and patient
      satisfaction and PCP time saved also were compared. RESULTS: 3,797 RARs for MRLMP
      eligible medications were approved in the month following MRLMP implementation in
      the intervention and control clinics. The intervention and control groups
      converted 49% and 29% of medications due for laboratory monitoring ( P < 0.001)
      and 56% and 33% of those due for blood pressure monitoring, respectively ( P =
      0.020). The intervention group PCPs were more likely than control group PCPs to
      report being "very satisfied" with the RAR process (80% vs. 27%, P = 0.015) and
      spent fewer minutes per day on refill requests (mean 17 vs. 23, P = 0.049). The
      intervention group pharmacists reported higher job satisfaction (mean index score
      22 vs. 18, P = 0.024), and intervention group patients reported higher
      satisfaction with the "readiness" of their prescription when they came to pick it
      up (91% vs. 80%, P = 0.004). CONCLUSION: A pharmacist-managed MRLMP resulted in
      improved process-related outcomes. Future studies should assess clinical
      outcomes.

PMID- 24030129
TI  - U.S. emergency departments visits resulting from poor medication adherence: 2005
      07.
AB  - OBJECTIVES: To describe characteristics and trends for emergency department
      visits related to medication nonadherence and to identify associations between
      patient characteristics and emergency department visits related to medication
      nonadherence. DESIGN: Retrospective cross-sectional study. SETTING: National
      Hospital Ambulatory Medical Care Survey (NHAMCS) from 2005 to 2007. PATIENTS:
      Patients who had an emergency department visit for medication nonadherence.
      INTERVENTION: NHAMCS data were weighted to yield national estimates of emergency
      department visits related to medication nonadherence. Descriptive frequencies
      were calculated for visits related and unrelated to medication adherence. A
      binary logistic regression model was used to identify covariates for
      nonadherence. MAIN OUTCOME MEASURES: National estimates of emergency department
      visits related to medication nonadherence. RESULTS: An estimated 456,209 +/-
      68,940 (mean +/- SD) nonadherence-related visits occurred. Of visits related to
      nonadherence, 29% resulted from mental health disorders. Significant covariates
      of nonadherence-related visits included age, payment source, and primary
      diagnosis. Visits for patients with mental illness (odds ratio 22.74 [95% CI
      14.68-34.20]), type 2 diabetes (15.80 [5.20-48.06]), nondependent abuse of drugs
      (11.85 [3.83-36.65]), or essential hypertension (11.06 [3.99-30.61]) were
      significantly associated with the probability that an emergency department visit
      was related to nonadherence. More than 20% of emergency department visits related
      to medication nonadherence resulted in hospital admission, whereas only 12.7% of
      visits unrelated to nonadherence resulted in hospital admission ( P < 0.0001).
      CONCLUSION: Medication nonadherence is an important problem. Targeting patients
      at high risk for nonadherence, especially patients with mental illness, may
      improve medication adherence and prevent future emergency department visits.

PMID- 24030131
TI  - Navigating complex patients using an innovative tool: the MTM Spider Web.
AB  - OBJECTIVE: To introduce a teaching tool that can be used to assess the complexity
      of medication therapy management (MTM) patients, prioritize appropriate
      interventions, and design patient-centered care plans for each encounter.
      SUMMARY: MTM patients are complex as a result of multiple comorbidities,
      medications, and socioeconomic and behavioral issues. Pharmacists who provide MTM
      services are required to synthesize a plethora of information (medical and
      nonmedical), evaluate and prioritize the clinical problems, and design a
      comprehensive patient-centered care plan. The MTM Spider Web is a visual tool to
      facilitate this process. A description is provided regarding how to build the MTM
      Spider Web using case-based scenarios. This model can be used to teach
      pharmacists, health professional students, and patients. CONCLUSION: The MTM
      Spider Web is an innovative teaching tool that can be used to teach pharmacists
      and students how to assess complex patients and design a patient-centered care
      plan to deliver the most appropriate medication therapy.

PMID- 24030130
TI  - Improving refill adherence and hypertension control in black patients: Wisconsin
      TEAM trial.
AB  - OBJECTIVE: To assess the effectiveness and sustainability of a 6-month Team
      Education and Adherence Monitoring (TEAM) intervention for black patients with
      hypertension in community chain pharmacies. DESIGN: Cluster randomized trial.
      SETTING: 28 chain pharmacies (14 TEAM and 14 control) in five Wisconsin cities
      from December 2006 to February 2009. PARTICIPANTS: 576 black patients with
      hypertension. INTERVENTION: Trained pharmacist-technician teams implemented a 6
      month intervention using scheduled visits, Brief Medication Questionnaires
      (BMQs), and novel toolkits for facilitating medication adherence and pharmacist
      feedback to patients and physicians. Control participants received patient
      information only. MAIN OUTCOME MEASURES: Refill adherence (>=80% days covered)
      and changes in systolic blood pressure (SBP), diastolic blood pressure, and blood
      pressure control using blinded assessments at 6 and 12 months. RESULTS: At
      baseline, all patients had blood pressure of 140/90 mm Hg or more. Of those
      eligible, 79% activated the intervention (mean 4.25 visits). Compared with
      control participants at 6 months, TEAM participants achieved greater improvements
      in refill adherence (60% vs. 34%, P < 0.001), SBP (-12.62 vs. -5.31 mm Hg, P <
      0.001), and blood pressure control (50% vs. 36%, P = 0.01). Six months after
      intervention discontinuation, TEAM participants showed sustained improvements in
      refill adherence ( P < 0.001) and SBP ( P = 0.004), though the difference in
      blood pressure control was not significant ( P < 0.05) compared with control
      participants. Analysis of intervention fidelity showed that patients who received
      the full intervention during months 1 through 6 achieved significantly greater 6-
      and 12-month improvements in refill adherence and blood pressure control compared
      with control participants. CONCLUSION: A team-based intervention involving
      community chain pharmacists, pharmacy technicians, and novel toolkits led to
      significant and sustained improvements in refill adherence and SBP in black
      patients with hypertension.

PMID- 24030132
TI  - Team-based approach to addressing simvastatin safety concerns.
AB  - OBJECTIVE: To describe acceptance of systematic and organized pharmacist
      interventions to address simvastatin safety concerns. SETTING: University of Utah
      Redwood Health Center and Pharmacy, June 2011 to February 2012. PRACTICE
      DESCRIPTION: Redwood Health Center is an outpatient multispecialty clinic
      associated with University of Utah Health Care with approximately 85,000 annual
      visits between primary care and specialty practices. In addition to filling
      approximately 175,000 prescriptions per year, pharmacists provide disease
      management and education under collaborative practice agreements. PRACTICE
      INNOVATION: All patients identified as being treated outside the revised
      simvastatin labeling were included (n = 158). After pharmacist review,
      recommendations were made to providers via the electronic medical record to
      promote adherence with the June 2011 Food and Drug Administration (FDA) safety
      guidelines. In addition to recommendations regarding the FDA guidelines (n = 76),
      additional recommendations were made to optimize treatment based on low-density
      lipoprotein cholesterol goal or laboratory evaluation (n = 25). MAIN OUTCOME
      MEASURES: Acceptance rate of recommendations and resources needed to provide
      pharmacist interventions. RESULTS: Recommendations were accepted 92% of the time
      without modification and 7% of the time with modification. Total pharmacist time
      to conduct the interventions was 21.5 hours, and 3.9 hours of technician time
      were spent contacting patients. CONCLUSION: Targeted pharmacist interventions
      were effective in promoting adherence with this complex medication safety alert.
      A standardized, comprehensive approach to patient assessment, including use of
      evidence to support pharmacist recommendations, resulted in a high level of
      acceptance by prescribers.

PMID- 24030133
TI  - New options for influenza vaccines: quadrivalent, recombinant, and cell culture.

PMID- 24030134
TI  - Pomalidomide, dabrafenib mesylate, and trametinib dimethyl sulfoxide.

PMID- 24030135
TI  - Science snippets. Pharmacist-led blood pressure intervention demonstrates
      positive results.

PMID- 24030137
TI  - Cognitive control and the COMT Val158Met polymorphism: genetic modulation of
      videogame training and transfer to task-switching efficiency.
AB  - The study investigated whether successful transfer of game-based cognitive
      improvements to untrained tasks might be modulated by preexisting neuro
      developmental factors, such as genetic variability related to the catechol-O
      methyltransferase (COMT)-an enzyme responsible for the degradation of dopamine.
      The COMT Val(158)Met genotype may differentially affect cognitive stability and
      flexibility, and we hypothesized that Val/Val homozygous individuals (who possess
      low prefrontal dopamine levels) show more pronounced cognitive flexibility than
      Met/-carriers (who possess high prefrontal dopamine levels). We trained
      participants, genotyped for the COMT Val(158)Met polymorphism on playing "Half
      Life 2", a first-person shooter game which has been shown to improve cognitive
      flexibility. Pre-training (baseline) and post-training measures of cognitive
      flexibility were acquired by means of a task-switching paradigm. As expected,
      Val/Val homozygous individuals showed larger beneficial transfer effects than
      Met/-carriers. Our findings support the idea that genetic predisposition
      modulates transfer effects and that playing first-person shooter games promotes
      cognitive flexibility in individuals with a suitable genetic predisposition. 

PMID- 24030138
TI  - Time-calibrated Milankovitch cycles for the late Permian.
AB  - An important innovation in the geosciences is the astronomical time scale. The
      astronomical time scale is based on the Milankovitch-forced stratigraphy that has
      been calibrated to astronomical models of paleoclimate forcing; it is defined for
      much of Cenozoic-Mesozoic. For the Palaeozoic era, however, astronomical forcing
      has not been widely explored because of lack of high-precision geochronology or
      astronomical modelling. Here we report Milankovitch cycles from late Permian
      (Lopingian) strata at Meishan and Shangsi, South China, time calibrated by recent
      high-precision U-Pb dating. The evidence extends empirical knowledge of Earth's
      astronomical parameters before 250 million years ago. Observed obliquity and
      precession terms support a 22-h length-of-day. The reconstructed astronomical
      time scale indicates a 7.793-million year duration for the Lopingian epoch, when
      strong 405-kyr cycles constrain astronomical modelling. This is the first
      significant advance in defining the Palaeozoic astronomical time scale, anchored
      to absolute time, bridging the Palaeozoic-Mesozoic transition. 

PMID- 24030139
TI  - Cellular and organismal toxicity of the anti-cancer small molecule, tolfenamic
      acid: a pre-clinical evaluation.
AB  - BACKGROUND/AIMS: The small molecule, Tolfenamic acid (TA) has shown anti-cancer
      activity in pre-clinical models and is currently in Phase I clinical trials at MD
      Anderson Cancer Center Orlando. Since specificity and toxicity are major concerns
      for investigational agents, we tested the effect of TA on specific targets, and
      assessed the cellular and organismal toxicity representing pre-clinical studies
      in cancer. METHODS: Panc1, L3.6pl, and MiaPaCa-2 (pancreatic cancer), hTERT
      HPNE(normal), and differentiated/un-differentiated SH-SY5Y (neuroblastoma) cells
      were treated with increasing concentrations of TA. Cell viability and effect on
      specific molecular targets, Sp1 and survivin were determined. Athymic nude mice
      were treated with vehicle or TA (50mg/kg, 3times/week for 6 weeks) and
      alterations in the growth pattern, hematocrit, and histopathology of gut, liver,
      and stomach were monitored. RESULTS: TA treatment decreased cell proliferation
      and inhibited the expression of Sp1 and survivin in cancer cells while only
      subtle response was observed in normal (hTERT-HPNE) and differentiated SH-SY5Y
      cells. Mice studies revealed no effect on body weight and hematocrit.
      Furthermore, TA regimen did not cause signs of internal-bleeding or damage to
      vital tissues in mice. CONCLUSION: These results demonstrate that TA selectively
      inhibits malignant cell growth acting on specific targets and its chronic
      treatment did not cause apparent toxicity in nude mice.

PMID- 24030140
TI  - Measurements of radon gas concentrations in dwellings of Al-Madinah Al-Munawarah
      province in Saudi Arabia.
AB  - Indoor radon concentration levels in a large number of dwellings in Al-Madinah Al
      Munawarah Province have been measured. Al-Madinah Al-Munawarah is in the western
      region of Saudi Arabia. It is the second holiest city in Islam after Mecca,
      because it is the burial place of the Islamic Prophet Muhammad. The city was
      divided into four regions: western (contains nine sites), eastern (contains six
      sites), northern (contains nine sites) and southern (contains five sites). Radon
      gas concentration was measured using the closed chamber technique employing 2*2
      cm(2) sheets of CR-39 solid-state nuclear track detectors. The detectors were
      kept for a period of 5 to 6 months from September 2010 to February 2011 in order
      to expose to radon gas. The results of the survey in the western and eastern
      sites showed that the overall minimum, maximum and average radon concentration
      levels were 20+/-1.6, 27+/-3.2 and 21+/-2.5 Bq m(-3), respectively. The lowest
      average radon concentration (20+/-1.6 Bq m(-3)) was found in Al Anabes and Al
      Suqya in the western region and Bani Dhafar in the eastern region, while the
      highest average concentration (27+/-3.2 Bq m(-3)) was found in Teeyba in the
      western region and Al 'Aridh in the eastern region, with an average of 21+/-2.5
      Bq m(-3) in the western and eastern sites of Al-Madinah Al-Munawarah. Also in the
      northern region, the minimum radon concentration was 20+/-1.6 Bq m(-3) in Oyun,
      while the maximum was 42+/-1.6 Bq m(-3) in Sayyed al Shuhadd and Hai Nasr. In the
      southern region, the minimum radon concentration was 25+/-2.6 Bq m(-3) at Hai Al
      Hejrah, while the maximum value was 37+/-2.6 Bq m(-3) at Al Awali and Dawadia.
      The average radon concentration was 26+/-2.5 Bq m(-3) for Al-Madinah Al-Munawarah
      (western, eastern, northern and southern regions). The corresponding annual
      effective dose E (mSv y(-1)) to public from (222)Rn and its progeny was estimated
      to be 0.66 mSv y(-1) as an average value for Al-Madinah Al-Munawarah. The authors
      concluded that all the dwellings monitored for indoor radon concentration and
      annual effective dose show values within the permissible level and this is a
      blessing from God that this area, which many visitors come from all over the
      world (to visit the burial place of the Prophet Muhammad), is safe. Consequently,
      the health hazards related to radiation are expected to be negligible. Occupants
      of these dwellings are relatively safe. 

PMID- 24030141
TI  - Patient radiation doses in uterine artery embolisation using Monte Carlo
      simulation.
AB  - This study aims at quantification of ovarian dose in uterine artery embolisation
      to study the level of optimisation of this dose. Individual anatomical data and
      all relevant exposure parameters of individual beam projections were recorded in
      52 patients who underwent uterine artery embolisation in two angiography units.
      The recorded information was used to calculate the individual ovarian doses by
      Monte Carlo simulation. The mean dose-area product was 196 Gy cm(2). The
      corresponding mean ovarian dose was 149 mGy. The performance of the two
      angiography units was analysed starting from these data. Dose-area product and
      ovarian doses obtained in this study were compared with data from other uterine
      artery embolisation patient dose studies. It was concluded that although the mean
      dose-area product and ovarian dose are acceptable, it is possible to optimise the
      procedure by improving the performance of the units. 

PMID- 24030142
TI  - Patient radiation exposure during different kyphoplasty techniques.
AB  - The scope of this study was to quantify patient radiation exposure during two
      different techniques of kyphoplasty (KP), which differ by a cement delivery
      method, in order to assess whether or not one of the two used methods can reduce
      the patient dose. Twenty patients were examined for this investigation. One X-ray
      fluoroscopy unit was used for localization, navigation and monitoring of cement
      delivery. The patient biometric data, the setting of the fluoroscope, the
      exposure time and the kerma-area product (KAP) were monitored in all the
      procedures for anteroposterior (AP) and lateral (LL) fluoroscopic projections in
      order to assess the range of radiation doses imparted to the patient. Theoretical
      entrance skin dose (ESD) and effective dose (E) were calculated from
      intraoperatively measured KAP. An average ET per procedure was 1.5+/-0.5 min for
      the manual injection technique (study A) and 1.4+/-0.4 min for the distance
      delivery technique (study B) in the AP plane, while 3.2+/-0.7 and 5.1+/-0.6 min
      in the lateral plane, respectively. ESD was estimated as an average of 0.10+/
      0.06 Gy for study A and 0.13+/-0.13 Gy for study B in the AP or/and 0.59+/-0.46
      and 1.05+/-0.36 Gy in the lateral view, respectively. The cumulative mean E was
      1.9+/-1.0 mSv procedure(-1) for study A and 3.6+/-0.9 mSv procedure(-1) for study
      B. Patient radiation exposure and associated effective dose from KP may be
      considerable. The technique of distance cement delivery appears to be slower than
      the manual injection technique and it requires a more protracted fluoroscopic
      control in the lateral projection, so that this system entails a higher amount of
      dose to the patient. 

PMID- 24030143
TI  - Radioactivity in the indoor building environment in Serbia.
AB  - Measurement of activity concentrations of radionuclides in building materials and
      radon in indoor space is important in the assessment of population exposures, as
      most individuals spend 80 % of their time indoors. This paper presents the
      results of activity concentration measurements of: radon emanated from the soil,
      radionuclides (226)Ra, (232)Th and (40)K in the soil, indoor radon in the city of
      Novi Sad (the capital city of Vojvodina) using charcoal canisters and indoor
      radon in the Vojvodina region using alpha-track detectors and the radioactivity
      of some building materials. Influences of floor level, space under the rooms,
      boarding, and the heating system on indoor radon accumulation in the Vojvodina
      province, situated in the northern part of Serbia, are also presented in this
      paper. The total effective dose and the activity concentration index are
      calculated applying the dose criteria recommended by the European Union for
      building materials. 

PMID- 24030144
TI  - Comparison of the performance of different instruments in the stray neutron field
      around the CERN Proton Synchrotron.
AB  - This paper discusses an intercomparison campaign carried out in several locations
      around the CERN Proton Synchrotron. The locations were selected in order to
      perform the measurements in different stray field conditions. Various neutron
      detectors were employed: ionisation chambers, conventional and extended range rem
      counters, both commercial and prototype ones, including a novel instrument called
      LUPIN, specifically conceived to work in pulsed fields. The attention was focused
      on the potential differences in the instrument readings due to dead-time losses
      that are expected to affect most commercial units. The results show that the
      ionisation chambers and LUPIN agree well with the expected H*(10) values, as
      derived from FLUKA simulations, showing no relevant underestimations even in
      strongly pulsed fields. On the contrary, the dead-time losses of the other rem
      counters induced an underestimation in pulsed fields that was more important for
      instruments characterised by a higher dead time. 

PMID- 24030145
TI  - [First guidelines of the Brazilian Society of Cardiology on Cardiopulmonary
      Resuscitation and Cardiovascular Emergency Care].

PMID- 24030146
TI  - Activation of TLR4 signaling promotes gastric cancer progression by inducing
      mitochondrial ROS production.
AB  - Chronic infection, such as Helicobacter pylori infection, has been associated
      with the development of gastric cancer (GC). Pathogen-associated molecular
      patterns can trigger inflammatory responses via Toll-like receptors (TLRs) in GC.
      Here we showed that Toll-like receptor 4 (TLR4) was highly expressed in GC cells
      and was associated with the aggressiveness of GC. The binding of
      lipopolysaccharide (LPS) to TLR4 on GC cells enhanced proliferation without
      affecting apoptosis. Higher level of reactive oxygen species (ROS) was induced
      after activation of TLR4 signaling in GC. Using oxidase inhibitors and
      antioxidants, we found that mitochondrial ROS (mROS) was major source of TLR4
      stimulated ROS generation. This elevated mROS production can be inhibited by
      diphenylene iodonium (DPI), and the blocking of the mROS production rather than
      ROS neutralization resulted in cell cycle arrest and the loss of mitochondrial
      potential, which were plausible reason for decreased cell viability. Furthermore,
      the increased mROS owing to TLR4 signaling resulted in the activation of Akt
      phosphorylation and NF-kappaB p65 nuclear translocation. Altogether, these
      results reveal a novel pathway linking innate immune signaling to GC cell
      proliferation, implicate mROS as an important component of cell survival signals
      and further establish mitochondria as hubs for GC therapies.

PMID- 24030147
TI  - Prostacyclin promotes oligodendrocyte precursor recruitment and remyelination
      after spinal cord demyelination.
AB  - Adult oligodendrocyte precursor cells (OPCs) are located adjacent to demyelinated
      lesion and contribute to myelin repair. The crucial step in remyelination is the
      migration of OPCs to the demyelinated area; however, the mechanism of OPC
      migration remains to be fully elucidated. Here we show that prostacyclin
      (prostaglandin I2, PGI2) promotes OPC migration, thereby promoting remyelination
      and functional recovery in mice after demyelination induced by injecting
      lysophosphatidylcholine (LPC) into the spinal cord. Prostacyclin analogs enhanced
      OPC migration via a protein kinase A (PKA)-dependent mechanism, and prostacyclin
      synthase expression was increased in the spinal cord after LPC injection.
      Notably, pharmacological inhibition of prostacyclin receptor (IP receptor)
      impaired remyelination and motor recovery, whereas the administration of a
      prostacyclin analog promoted remyelination and motor recovery after LPC
      injection. Our results suggest that prostacyclin could be a key molecule for
      facilitating the migration of OPCs that are essential for repairing demyelinated
      areas, and it may be useful in treating disorders characterized by demyelination.

PMID- 24030148
TI  - A new platinum(II) compound anticancer drug candidate with selective cytotoxicity
      for breast cancer cells.
AB  - [Pt(O,O'-acac)(gamma-acac)(DMS)] (PtAcD) is able to induce apoptosis in various
      human cancer cells, including the cisplatin-resistant human breast carcinoma MCF
      7 cells. Here, to confirm that PtAcD has the potentiality for therapeutic
      intervention, we studied its effects in primary cultured epithelial breast cells
      obtained from cancers and also from the corresponding histologically proven non
      malignant tissue adjacent to the tumor. We demonstrated that PtAcD (1) is more
      cytotoxic in cancer than in normal breast cells; (2) activated NAD(P)H oxidase,
      leading to PKC-zeta and PKC-alpha translocations; (3) activated antiapoptotic
      pathways based on the PKC-alpha, ERK1/2 and Akt kinases; (4) activated PKC-zeta
      and, only in cancer cell PKC-delta, responsible for the sustained phosphorylation
      of p38 and JNK1/2, kinases both of which are involved in the mitochondrial
      apoptotic process. Moreover, crosstalk between ERK/Akt and JNK/p38 pathways
      affected cell death and survival in PtAcD-treated breast cell. In conclusion,
      this study adds and extends data that highlight the pharmacological potential of
      PtAcD as an anti breast cancer drug.

PMID- 24030149
TI  - Loss of Pde6 reduces cell body Ca(2+) transients within photoreceptors.
AB  - Modulation of Ca(2+) within cells is tightly regulated through complex and
      dynamic interactions between the plasma membrane and internal compartments. In
      this study, we exploit in vivo imaging strategies based on genetically encoded
      Ca(2+) indicators to define changes in perikaryal Ca(2+) concentration of intact
      photoreceptors. We developed double-transgenic zebrafish larvae expressing GCaMP3
      in all cones and tdTomato in long-wavelength cones to test the hypothesis that
      photoreceptor degeneration induced by mutations in the phosphodiesterase-6 (Pde6)
      gene is driven by excessive [Ca(2+)]i levels within the cell body. Arguing
      against Ca(2+) overload in Pde6 mutant photoreceptors, simultaneous analysis of
      cone photoreceptor morphology and Ca(2+) fluxes revealed that degeneration of
      pde6c(w59) mutant cones, which lack the cone-specific cGMP phosphodiesterase, is
      not associated with sustained increases in perikaryal [Ca(2+)]i. Analysis of
      [Ca(2+)]i in dissociated Pde6beta(rd1)mouse rods shows conservation of this
      finding across vertebrates. In vivo, transient and Pde6-independent Ca(2+)
      elevations ('flashes') were detected throughout the inner segment and the
      synapse. As the mutant cells proceeded to degenerate, these Ca(2+) fluxes
      diminished. This study thus provides insight into Ca(2+) dynamics in a common
      form of inherited blindness and uncovers a dramatic, light-independent modulation
      of [Ca(2+)]i that occurs in normal cones.

PMID- 24030150
TI  - Preclinical screening of histone deacetylase inhibitors combined with ABT-737,
      rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma.
AB  - Multiple myeloma (MM) is an incurable malignancy with an unmet need for
      innovative treatment options. Histone deacetylase inhibitors (HDACi) are a new
      class of anticancer agent that have demonstrated activity in hematological
      malignancies. Here, we investigated the efficacy and safety of HDACi (vorinostat,
      panobinostat, romidepsin) and novel combination therapies using in vitro human MM
      cell lines and in vivo preclinical screening utilizing syngeneic transplanted
      Vk*MYC MM. HDACi were combined with ABT-737, which targets the intrinsic
      apoptosis pathway, recombinant human tumour necrosis factor-related apoptosis
      inducing ligand (rhTRAIL/MD5-1), that activates the extrinsic apoptosis pathway
      or the DNA methyl transferase inhibitor 5-azacytidine. We demonstrate that in
      vitro cell line-based studies provide some insight into drug activity and
      combination therapies that synergistically kill MM cells; however, they do not
      always predict in vivo preclinical efficacy or toxicity. Importantly, utilizing
      transplanted Vk*MYC MM, we report that panobinostat and 5-azacytidine synergize
      to prolong the survival of tumor-bearing mice. In contrast, combined
      HDACi/rhTRAIL-based strategies, while efficacious, demonstrated on-target dose
      limiting toxicities that precluded prolonged treatment. Taken together, our
      studies provide evidence that the transplanted Vk*MYC model of MM is a useful
      screening tool for anti-MM drugs and should aid in the prioritization of novel
      drug testing in the clinic.

PMID- 24030151
TI  - Cell-nonautonomous inhibition of radiation-induced apoptosis by dynein light
      chain 1 in Caenorhabditis elegans.
AB  - The evolutionarily conserved process of programmed cell death, apoptosis, is
      essential for development of multicellular organisms and is also a protective
      mechanism against cellular damage. We have identified dynein light chain 1 (DLC
      1) as a new regulator of germ cell apoptosis in Caenorhabditis elegans. The DLC-1
      protein is highly conserved across species and is a part of the dynein motor
      complex. There is, however, increasing evidence for dynein-independent functions
      of DLC-1, and our data describe a novel dynein-independent role. In mammalian
      cells, DLC-1 is important for cellular transport, cell division and regulation of
      protein activity, and it has been implicated in cancer. In C. elegans, we find
      that knockdown of dlc-1 by RNA interference (RNAi) induces excessive apoptosis in
      the germline but not in somatic cells during development. We show that DLC-1
      mediates apoptosis through the genes lin-35, egl-1 and ced-13, which are all
      involved in the response to ionising radiation (IR)-induced apoptosis. In
      accordance with this, we show that IR cannot further induce apoptosis in dlc
      1(RNAi) animals. Furthermore, we find that DLC-1 is functioning cell
      nonautonomously through the same pathway as kri-1 in response to IR-induced
      apoptosis and that DLC-1 regulates the levels of KRI-1. Our results strengthen
      the notion of a highly dynamic communication between somatic cells and germ cells
      in regulating the apoptotic process.

PMID- 24030152
TI  - Interdigital cell death in the embryonic limb is associated with depletion of
      Reelin in the extracellular matrix.
AB  - Interdigital cell death is a physiological regression process responsible for
      sculpturing the digits in the embryonic vertebrate limb. Changes in the intensity
      of this degenerative process account for the different patterns of interdigital
      webbing among vertebrate species. Here, we show that Reelin is present in the
      extracellular matrix of the interdigital mesoderm of chick and mouse embryos
      during the developmental stages of digit formation. Reelin is a large
      extracellular glycoprotein which has important functions in the developing
      nervous system, including neuronal survival; however, the significance of Reelin
      in other systems has received very little attention. We show that reelin
      expression becomes intensely downregulated in both the chick and mouse
      interdigits preceding the establishment of the areas of interdigital cell death.
      Furthermore, fibroblast growth factors, which are cell survival signals for the
      interdigital mesoderm, intensely upregulated reelin expression, while BMPs, which
      are proapototic signals, downregulate its expression in the interdigit. Gene
      silencing experiments of reelin gene or its intracellular effector Dab-1
      confirmed the implication of Reelin signaling as a survival factor for the limb
      undifferentiated mesoderm. We found that Reelin activates canonical survival
      pathways in the limb mesoderm involving protein kinase B and focal adhesion
      kinase. Our findings support that Reelin plays a role in interdigital cell death,
      and suggests that anoikis (apoptosis secondary to loss of cell adhesion) may be
      involved in this process.

PMID- 24030153
TI  - Metastatic SW620 colon cancer cells are primed for death when detached and can be
      sensitized to anoikis by the BH3-mimetic ABT-737.
AB  - Anoikis, a Bax-dependent apoptosis triggered by detachment from the extracellular
      matrix, is often inhibited in metastatic cancer cells. Using a couple of isogenic
      human colon cancer cell lines derived either from the primary tumor (SW480) or
      from a lymph node metastasis (SW620), we found that only SW480 cells were
      sensitive to anoikis. Bim upregulation but not Mcl-1 degradation was determined
      to be a critical factor of anoikis initiation in SW480 cells. ERK-mediated
      phosphorylation targets Bim for ubiquitination and proteasomal degradation. A MEK
      inhibitor (PD0325901) was able to increase Bim expression in SW620 cells and to
      sensitize these cells to anoikis. Thus, in both cell lines anoikis is under the
      control of proteins of the Bcl-2 family. Most interestingly, the BH3-mimetic ABT
      737 was found not only to increase the level of apoptosis in suspended SW480
      cells but also to sensitize SW620 cells to anoikis. Accordingly, both cell lines
      cultured in suspension were found to be primed for death, as determined by the
      detection of Bcl-2:Bim and Bcl-xL:Bim complexes. In contrast, adherent SW480 and
      SW620 cells were resistant to ABT-737. This indicates that, whether or not they
      undergo anoikis, colon cancer cells that have detached from the extracellular
      matrix might go through a transient state, where they are sensitive to BH3
      mimetics. This would confer to compounds such as Navitoclax or ABT-199 a
      therapeutic window where they could have anti-metastatic potential.

PMID- 24030154
TI  - Smac mimetic and demethylating agents synergistically trigger cell death in acute
      myeloid leukemia cells and overcome apoptosis resistance by inducing necroptosis.
AB  - Evasion of apoptosis, for example, by inhibitor of apoptosis (IAP) proteins,
      contributes to treatment resistance and poor outcome in acute myeloid leukemia
      (AML). Here we identify a novel synergistic interaction between the small
      molecule second mitochondria-derived activator of caspases (Smac) mimetic BV6,
      which antagonizes X-linked IAP, cellular IAP (cIAP)1 and cIAP2, and the
      demethylating agents 5-azacytidine or 5-aza-2'-deoxycytidine (DAC) to induce cell
      death in AML cells, including apoptosis-resistant cells. Calculation of
      combination index (CI) confirms that this drug combination is highly synergistic
      (CI 0.02-0.4). In contrast, BV6 and DAC at equimolar concentrations do not cause
      synergistic toxicity against normal peripheral blood lymphocytes, pointing to
      some tumor cell selectivity. Molecular studies reveal that BV6 and DAC cooperate
      to trigger the activation of caspases, mitochondrial perturbations and DNA
      fragmentation, consistent with apoptotic cell death. However, the broad-range
      caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk)
      fails to protect against BV6/DAC-induced cell death and even significantly
      increases the percentage of Annexin-V/propidium iodide double-positive cells.
      Importantly, BV6/DAC-induced cell death in the presence of zVAD.fmk is
      significantly reduced by pharmacological inhibition of key components of
      necroptosis signaling, that is, receptor-interacting protein (RIP) 1 using
      necrostatin-1 or mixed lineage kinase domain-like protein (MLKL) using
      necrosulfonamide. This indicates a switch from BV6/DAC-induced cell death from
      apoptosis to necroptosis upon caspase inhibition. Thus, BV6 cooperates with
      demethylating agents to induce cell death in AML cells and circumvents apoptosis
      resistance via a switch to necroptosis as an alternative mode of cell death. The
      identification of a novel synergism of BV6 and demethylating agents has important
      implications for the development of new treatment strategies for AML.

PMID- 24030156
TI  - A new strategy for designing a graphene oxide-based DNA hairpin probe:
      fluorescence upon switching the orientation of the sticky end.
AB  - Here we report a new strategy for designing a graphene oxide (GO)-quenched dye
      labeled DNA hairpin probe by utilizing the sticky end adsorbed onto the GO
      surface. Only introduction of target DNA can alter the orientation of the sticky
      end, causing the dye to move apart from the GO surface, resulting in fluorescence
      restoration. 

PMID- 24030155
TI  - Overexpression of 4EBP1, p70S6K, Akt1 or Akt2 differentially promotes
      Coxsackievirus B3-induced apoptosis in HeLa cells.
AB  - Our previous studies have shown that the inhibition of phosphatidylinositol 3
      kinase (PI3K) or mTOR complex 1 can obviously promote the Coxsackievirus B3
      (CVB3)-induced apoptosis of HeLa cells by regulating the expression of
      proapoptotic factors. To further illustrate it, Homo sapiens eIF4E-binding
      protein 1 (4EBP1), p70S6 kinase (p70S6K), Akt1 and Akt2 were transfected to HeLa
      cells, respectively. And then, we established the stable transfected cell lines.
      Next, after CVB3 infection, apoptosis in different groups was determined by flow
      cytometry; the expressions of Bim, Bax, caspase-9 and caspase-3 were examined by
      real-time fluorescence quantitative PCR and western blot analysis; the expression
      of CVB3 mRNA and viral capsid protein VP1 were also analyzed by real-time
      fluorescence quantitative PCR, western blot analysis and immunofluorescence,
      respectively. At the meantime, CVB3 replication was observed by transmission
      electron microscope. We found that CVB3-induced cytopathic effect and apoptosis
      in transfected groups were more obvious than that in controls. Unexpectedly,
      apoptosis rate in Akt1 group was higher than others at the early stage after
      viral infection and decreased with the viral-infected time increasing, which was
      opposite to other groups. Compared with controls, the expression of CVB3 mRNA was
      increased at 3, 6, 12 and 24 h postinfection (p. i.) in all groups. At the
      meantime, VP1 expression in 4EBP1 group was higher than control during the
      process of infection, while the expressions in the other groups were change
      dynamically. Moreover, overexpression of 4EBP1 did not affect the mRNA
      expressions of Bim, Bax, caspase-9 and caspase-3; while protein expressions of
      Bim and Bax were decreased, the self-cleavages of caspase-9 and caspase-3 were
      stimulated. Meanwhile, overexpression of p70S6K blocked the CVB3-induced Bim, Bax
      and caspase-9 expressions but promoted the self-cleavage of caspase-9. In the
      Akt1 group, it is noteworthy that the expressions of Bim protein were higher than
      controls at 3 and 6 h p. i. but lower at 24 h p. i., and the expression of Bax
      protein were higher at 6 and 24 h p. i., while their mRNA expressions were all
      decreased. Furthermore, overexpression of Akt1 stimulated the procaspase-9 and
      procaspase-3 expression but blocked their self-cleavages. Overexpression of Akt2,
      however, had little effect on Bim, Bax and caspase-3, while prevented caspase-9
      from self-cleavage at the late stage of CVB3 infection. As stated above, our
      results demonstrated that overexpression of 4EBP1, p70S6K, Akt1 or Akt2 could
      promote the CVB3-induced apoptosis in diverse degree via different mediating ways
      in viral replication and proapoptotic factors in BcL-2 and caspase families. As
      4EBP1, p70S6K and Akt are the important substrates of PI3K and mammalian target
      of rapamycin (mTOR), we further illustrated the role of PI3K/Akt/mTOR signaling
      pathway in the process of CVB3-induced apoptosis.

PMID- 24030158
TI  - How "healthy" is circuit resistance training following paraplegia? Kinematic
      analysis associated with shoulder mechanical impingement risk.
AB  - The purpose of the study was to determine whether wheelchair-based circuit
      resistance training (CRT) exercises place the shoulder at risk for mechanical
      impingement. Using a novel approach, we created a mechanical impingement risk
      score for each exercise by combining scapular and glenohumeral kinematic and
      exposure data. In a case series design, 18 individuals (25-76 yr old) with
      paraplegia and without substantial shoulder pain participated. The mean
      mechanical impingement risk scores at 45-60 degrees humerothoracic elevation were
      rank-ordered from lowest to highest risk as per subacromial mechanical
      impingement risk: overhead press (0.6 +/- 0.5 points), lat pulldown (1.2 +/- 0.5
      points), chest press (2.4 +/- 2.8 points), row (2.7 +/- 1.6 points), and rickshaw
      (3.4 +/- 2.3 points). The mean mechanical impingement risk scores at 105-120
      degrees humerothoracic elevation were rank-ordered from lowest to highest risk as
      per internal mechanical impingement risk: lat pulldown (1.2 +/- 0.5 points) and
      overhead press (1.3 +/- 0.5 points). In conclusion, mechanical impingement risk
      scores provided a mechanism to capture risk associated with CRT. The rickshaw had
      the highest subacromial mechanical risk, whereas the overhead press and lat
      pulldown had the highest internal mechanical impingement risk. The rickshaw was
      highlighted as the most concerning exercise because it had the greatest
      combination of magnitude and exposure corresponding with increased subacromial
      mechanical impingement risk. 

PMID- 24030159
TI  - Semiconducting layered technetium dichalcogenides: insights from first
      principles.
AB  - The structures and properties of layered technetium dichalcogenides TcX2 (X = S,
      Se, Te) have been investigated using density functional theory. The equilibrium
      structures of TcSe2 and TcTe2, adopting distorted Cd(OH)2-type unit cells similar
      to TcS2, are reported for the first time at the atomic level, along with their
      electronic properties. In contrast to previous X-ray diffraction analyses,
      calculations reveal that stoichiometric TcTe2 is not isomorphous to the high
      temperature monoclinic phase beta-MoTe2. All three compounds are found to be
      semiconductors with calculated band gaps of 0.9 eV for TcS2, 0.8 eV for TcSe2,
      and 0.3 eV for TcTe2. The thermal properties of these TcX2 compounds have also
      been predicted using phonon frequencies calculated with density functional
      perturbation theory. 

PMID- 24030160
TI  - Time is brain: starting therapeutic hypothermia within three hours after birth
      improves motor outcome in asphyxiated newborns.
AB  - OBJECTIVE: Therapeutic hypothermia (HT) is the standard treatment for newborns
      after perinatal asphyxia. Preclinical studies report that HT is more effective
      when started early. METHODS: Eighty cooled newborns were analyzed and grouped
      according to when cooling was started after birth: early (<=180 min) or late
      (>181 min). For survivors we analyzed whether starting cooling early was
      associated with a better psychomotor or mental developmental index (PDI or MDI,
      Bayley Scales of Infant Development II) than late cooling. RESULTS: Forty-three
      newborns started cooling early and 37 started late. There was no significant
      difference in the severity markers of perinatal asphyxia between the groups;
      however, nonsurvivors (n = 15) suffered more severe asphyxia and had
      significantly lower centiles for weight (BWC; p = 0.009). Of the 65 infants that
      survived, 35 were cooled early and 30 were cooled late. There was no difference
      in time to start cooling between those who survived and those who did not. For
      survivors, median PDI (IQR) was significantly higher when cooled early [90 (77
      99)] compared to being cooled later [78 (70-90); p = 0.033]. There was no
      increase in cardiovascular adverse effects in those cooled early. There was no
      significant difference in MDI between early and late cooling [93 (77-103) vs. 89
      (76-106), p = 0.594]. CONCLUSION: Starting cooling before 3 h of age in surviving
      asphyxiated newborns is safe and significantly improves motor outcome. Cooling
      should be initiated as soon as possible after birth in eligible infants.

PMID- 24030161
TI  - Oblique subduction modelling indicates along-trench tectonic transport of
      sediments.
AB  - Convergent plate margins are currently distinguished as 'accretional' or
      'erosional', depending on the tendency to accumulate sediments, or not, at the
      trench. Accretion and erosion can coexist along the same margin and we have
      noticed that this mostly occurs where subduction is oblique. Here we show that at
      oblique subduction zones, sediments that enter the trench are first buried, and
      later migrate laterally parallel to the trench and at various depths. Lateral
      migration of sediments continues until they reach a physical barrier where they
      begin to accumulate. The accretionary wedge size decreases along the trench
      moving away from the barrier. We therefore suggest that the gradual variation of
      the accretionary wedge size and sediment amount at the trench along one single
      subduction zone, as observed in many active plate margins worldwide, can be
      explained by the lateral tectonic migration of sediments driven by obliquity of
      subduction as well. 

PMID- 24030162
TI  - Twenty-four-hour intraocular pressure monitoring: it's about time.

PMID- 24030163
TI  - Informed consent, the value of trust,  and hedons.

PMID- 24030164
TI  - Magnetic resonance imaging of the pelvic floor: from clinical to biomechanical
      imaging.
AB  - This article reviews the current role of magnetic resonance imaging in the study
      of the pelvic floor anatomy and pelvic floor dysfunction. The application of
      static and dynamic magnetic resonance imaging in the clinical context and for
      biomechanical simulation modeling is assessed, and the main findings are
      summarized. Additionally, magnetic resonance-based diffusion tensor imaging is
      presented as a potential tool to evaluate muscle fiber morphology. In this
      article, focus is set on pelvic floor muscle damage related to urinary
      incontinence and pelvic organ prolapse, sometimes as a consequence of vaginal
      delivery. Modeling applications that evaluate anatomical and physiological
      properties of pelvic floor are presented to further illustrate their particular
      characteristics. Finally, finite element method is described as a method for
      modeling and analyzing pelvic floor structures' biomechanical performance, based
      on material and behavioral properties of the tissues, and considering pressure
      loads that mimic real-life conditions such as active contraction or Valsalva
      maneuver. 

PMID- 24030165
TI  - Functional and molecular imaging techniques in aortic aneurysm disease.
AB  - PURPOSE OF REVIEW: Functional and molecular aortic imaging has shown great
      promise for evaluation of aortic disease, and may soon augment conventional
      assessment of aortic dimensions for the clinical management of patients. RECENT
      FINDINGS: A range of imaging techniques is available for evaluation of patients
      with aortic disease. Magnetic resonance blood flow imaging can identify
      atherosclerosis prone aortic regions and may be useful for predicting aneurysm
      growth. Computational modeling can demonstrate significant differences in wall
      stress between abdominal aortic aneurysms of similar size and may better predict
      rupture than diameter alone. Metabolic imaging with fluorodeoxyglucose-PET [(FDG)
      PET] can identify focal aortic wall inflammation that may portend rapid
      progression of disease. Molecular imaging with probes that target collagen and
      elastin can directly exhibit changes in the vessel wall associated with disease.
      SUMMARY: The complexity of aortic disease is more fully revealed with new
      functional imaging techniques than with conventional anatomic analysis alone.
      This may better inform surveillance imaging regimens, medical management and
      decisions regarding early intervention for aortic disease.

PMID- 24030166
TI  - Changes of ticagrelor formulary tiers in the USA: targeting private insurance
      providers away from government-funded plans.
AB  - CONTEXT: Ticagrelor (Brilinta(r)) is a new oral reversible antiplatelet agent
      approved by the FDA in July 2011 based on the results of the PLATO (Platelet
      Inhibition and Patient Outcomes) trial. However, despite very favorable and broad
      indications, the current clinical utilization of ticagrelor is woefully small.
      OBJECTIVE: We aimed to compare ticagrelor formulary tiers for major private (n =
      8) and government-funded (n = 4) insurance providers for 2012-2013. RESULTS: Over
      the last year, ticagrelor placement improved, becoming a preferred drug (from
      Tier 3 in 2012 to Tier 2 in 2013) for Medco, moving from Tier 4 (with a prior
      approval requirement) to Tier 3 (no prior approval) for the United Health Care
      Private Plan and achieving Tier 3 status for Apex in 2013. In contrast,
      ticagrelor placement did not improve for New York Medicaid, retaining Tier 3
      status. In addition, many Medicare Part D formularies have significantly worse
      coverage than most private plans. For example, Humana Medicare Part D has Tier 3
      status requiring step therapy and quantity limits, SilverScript (CVS Caremark)
      Part D is Tier 3 and the American Association of Retired Persons (United Health
      Care) Medicare Part D is Tier 4 requiring prior approval. CONCLUSIONS: Ticagrelor
      formulary placement is significantly better for most private providers than for
      government-funded plans, which may possibly be due to the selective targeting of
      private insurance providers and the simultaneous avoidance of government-funded
      plans.

PMID- 24030167
TI  - A genetically modified broad-spectrum strain of Bacillus thuringiensis toxic
      against Holotrichia parallela, Anomala corpulenta and Holotrichia oblita.
AB  - Cry8Ea1 from Bacillus thuringiensis strain Bt185 has insecticidal activity
      against Holotrichia parallela. Cry8Ca2 from strain HBF-1 is effective against
      Anomala corpulenta. Cry8Ga1 from strain HBF-18 is toxic to H. oblita. Given the
      need to broaden the spectrum of B. thuringiensis, a broad-spectrum coleopteran
      active strain of B. thuringiensis, BIOT185, engineered to express multiple cry
      genes, including cry8Ea1, cry8Fa1 and cry8Ca2, was created by homologous
      recombination introducing the cry8Ca2 into the B. thuringiensis strain Bt185 by
      Liu et al. (Appl Microbiol Biotechnol 87:243-249, 2010). To further broaden the
      spectrum, an engineered B. thuringiensis strain BIOT1858G was constructed by
      introducing the recombinant plasmid pSTK-8G containing cry8Ga1 into the
      engineered B. thuringiensis strain BIOT185. PCR and Southern blotting
      demonstrated that the cry8Ga1 gene was transferred to the novel strain BIOT1858G.
      SDS-PAGE and RT-PCR confirmed the normal expression and transcription of the
      cry8Ga1 gene in addition to the cry8Ea1, cry8Fa1 and cry8Ca2 genes. Bioassays of
      BIOT1858G indicated that the recombinant strain broadened the spectrum against
      not only H. parallela susceptible to the Cry8E protein and A. corpulenta
      susceptible to the Cry8C protein but also H. oblita susceptible to the Cry8G
      protein. The pesticide could also decrease the cost of production and field
      labor. 

PMID- 24030168
TI  - Characterization of eubacterial and archaeal community diversity in the pit mud
      of Chinese Luzhou-flavor liquor by nested PCR-DGGE.
AB  - The aim of this study was to investigate and compare the microbial community
      structures of eubacteria and archaea in the pit mud of Chinese Luzhou-flavor
      liquor from the wall (C(w)) and bottom (C(b)) of cellar through nested PCR
      denaturing gradient gel electrophoresis (DGGE). The Shannon-Wiener index (H)
      calculated from the DGGE profiles showed that the community diversities of
      eubacteria and archaea in samples from C(b) were almost higher than that from
      C(w). In addition, cluster analysis of the DGGE profiles revealed that some
      differences were found in the microbial community structure in samples from
      different locations. The closely relative microorganisms of all eubacterial 16S
      rRNA gene sequences fell into four phyla (Firmicutes, Proteobacteria,
      Bacteroidetes and Actinobacteria), including 12 genera and 2 uncultured
      eubacteria. Moreover, 37.1% eubacteria were affiliated with Clostridium.
      Particularly, genus Acinetobacter was absent in all samples from C(b) but present
      in all samples from C(w). The closely relative microorganisms of all archaeal 16S
      rRNA gene sequences fell into four genera, which included Methanobrevibacter,
      Methanoculleus, Methanobacterium and Methanosaeta, while the dominant archaea in
      samples from C(w) and C(b) were similar. Results presented in this study provide
      further understanding of the spatial differences in microbial community structure
      in the pit mud, and is of great importance for the production and quality
      improvement of Luzhou-flavor liquor.

PMID- 24030169
TI  - Cloning and characterization of squalene synthase gene from Poria cocos and its
      up-regulation by methyl jasmonate.
AB  - Squalene synthase (SQS) catalyzes the condensation of two molecules of farnesyl
      diphosphate to give presqualene diphosphate and the subsequent rearrangement to
      form squalene. The gene encoding squalene synthase was cloned from Poria cocos by
      degenerate PCR and inverse PCR. The open reading frame of the gene is 1,497 bp,
      which encodes 499 amino acid residues. A phylogenetic analysis revealed that P.
      cocos SQS belonged to the fungus group, and was more closely related to the SQS
      of Ganoderma lucidum than other fungi. The treatment of P. cocos with methyl
      jasmonate (MeJA) significantly enhanced the transcriptional level of P. cocos sqs
      gene and the content of squalene in P. cocos. The transcriptional level of sqs
      gene was approximately fourfold higher than the control sample and the squalene
      content reached 128.62 MUg/g, when the concentration of MeJA was 300 MUM after 72
      h induction.

PMID- 24030170
TI  - Isolation and algicidal characterization of Bowmanella denitrificans S088 against
      Chlorella vulgaris.
AB  - One strain of algicidal bacterium, named as S088, was isolated from the intestine
      of healthy sea cucumbers (Stichopus horrens) in the South China Sea. Based on the
      analysis of its biochemical characteristics and 16S rDNA gene sequence, S088 was
      identified as Bowmanella denitrificans. Importantly, the algicidal activity of
      S088 on Chlorella vulgaris was characterized in this study. The initial densities
      of bacterial and algal cell showed strong influence on the removal rates of
      chlorophyll a. When the strain S088 was cultured under a complete darkness
      condition at 30  degrees C, its algicidal activity reached the highest level.
      Furthermore, it was found that the filtered supernatant from bacterial cultures
      had full algicidal activity, suggesting that the secreted compounds from S088 are
      involved in the observed algicidal action of S088. Moreover, the algicidal
      compounds were heat tolerant and had no cytotoxicity against fish cells,
      indicating that S088 would have a promising application as a safe probiotics for
      S. horrens. Finally, this is the first report about the algicidal activities in
      B. denitrificans.

PMID- 24030171
TI  - Surgical outcomes and predictors of stroke in a North American white and African
      American moyamoya population.
AB  - BACKGROUND: The majority of moyamoya surgical series have been confined to Asian
      and pediatric populations. Few have studied demographics, risk factors, and
      outcomes in adult North American populations. OBJECTIVE: To examine outcomes
      after revascularization for moyamoya in white and African American adults and to
      assess for predictors of recurrent stroke. METHODS: A retrospective review of 75
      non-Asian patients undergoing 110 procedures at the Mayo Clinic was performed.
      Demographics, known moyamoya associations, cerebrovascular risk factors, and
      autoimmune diseases were recorded. Primary outcomes for vascular events were
      assessed with Kaplan-Meier analysis. Fisher exact methods were used to evaluate
      for associations with recurrent events. RESULTS: Mean age was 42 years, and mean
      follow-up was 47 months. Seventy-one of the 75 patients were white. The majority
      had bilateral disease (n = 49). Perioperative ischemic events occurred in 5
      patients (4.5%). The 5- and 10-year event rates were 5.8% and 9.9%. Significant
      associations were found with a history of thyroid disease (P = .05) and recurrent
      stroke. A trend was also found between hypertension and autoimmune disease with
      recurrent stroke. CONCLUSION: Outcomes were favorable with revascularization in
      this subset with moyamoya. A significant association between a history of thyroid
      disease and recurrent stroke was found. Additionally, high prevalences of
      autoimmune disease, hypertension, and thyroid disease were found in our cohort,
      suggesting that they may play a role in the pathophysiology and progression of
      moyamoya disease in this population. A new classification for moyamoya is
      proposed based on these data.

PMID- 24030172
TI  - Seizure outcomes after corpus callosotomy for drop attacks.
AB  - BACKGROUND: Medically intractable epilepsy involving drop attacks can be
      difficult to manage and negatively affect quality of life. Most studies
      investigating the effect of corpus callosotomy (CC) on seizures have been
      limited, focusing on the pediatric population or drop seizures alone, with little
      attention to other factors influencing seizure outcome. OBJECTIVE: To assess
      seizure outcomes after CC in adults and children. METHODS: Retrospective analysis
      was performed on all patients who underwent CC (anterior two thirds, 1- or 2
      stage complete) at our institution between 1990 and 2011. Change in frequency
      after CC was assessed for drop seizures and other seizure types. Multiple factors
      were evaluated for impact on seizure outcome. RESULTS: Fifty patients met
      inclusion criteria. The median age was 1.5 years at seizure onset and 17 years at
      time of surgery. Anterior two-thirds CC was performed in 28 patients, 1-stage
      complete in 17, and 2-stage complete in 5. All 3 groups experienced a significant
      decrease in drop seizures (P < .001, P < .001, and P = .020, respectively), with
      40% experiencing complete resolution, and 64% dropping at least 1 frequency
      category. Other seizure types significantly decreased in anterior two-thirds CC
      and 1-stage complete (P = .0035, P = .001, respectively). Younger age at surgery
      correlated with better seizure outcomes (P = .043). CONCLUSION: CC for medically
      refractory generalizing epilepsy is effective for both drop seizures and other
      seizure types. CC should be considered soon after a patient has been deemed
      medically refractory because earlier age at surgery results in lower risk and
      better outcome.

PMID- 24030173
TI  - Benefit of a sharp computed tomography angiography reconstruction kernel for
      improved characterization of intracranial aneurysms.
AB  - BACKGROUND: Computed tomography angiography (CTA) is the first-line imaging
      modality used for cerebral aneurysms because of its speed and sensitivity for
      detection, although digital subtraction angiography is often required for more
      detailed aneurysm shape delineation. OBJECTIVE: To determine whether a sharper
      CTA reconstruction kernel can better characterize an aneurysm and improve
      decision-making before intervention. METHODS: Fifteen patients presenting with
      aneurysmal subarachnoid hemorrhage underwent 64-row CTA. CTA data were
      reconstructed using the default H20f smooth kernel and a H60f sharp kernel and
      compared with contemporaneous catheter 3-dimensional rotational angiography
      (3DRA). Aneurysm neck, width, and aspect ratio measurements were made using
      intensity line plots of identical projections on all imaging datasets and
      compared by matched-pair statistics. RESULTS: Aneurysm neck measurements from the
      H20f smooth kernel revealed overestimation compared with both the sharp kernel
      (greater by 0.64 +/- 0.21 mm, P < .01) and 3DRA (greater by 0.68 +/- 0.19 mm, P <
      .01). There was no statistically significant difference between 3DRA and the
      sharp kernel CTA measurements. Neck measurements correlated well between the H60f
      kernel and 3DRA but not between the H20f Kernel and 3DRA (R 0.97 vs 0.86).
      CONCLUSION: H60f sharp CTA kernel reconstruction provides more accurate anatomic
      characterization of cerebral aneurysms than the H20f smooth kernel at the expense
      of less visually pleasing reconstructions. Because it does not require additional
      contrast, radiation, or imaging hardware and is more similar to 3DRA, it may aid
      in selecting the appropriate treatment strategy before to evaluation by catheter
      based angiography.

PMID- 24030174
TI  - The blunt truth behind coiling vs clipping: consumers as decision-drivers.

PMID- 24030175
TI  - In reply.

PMID- 24030176
TI  - In reply.

PMID- 24030177
TI  - In reply.

PMID- 24030178
TI  - Aspirin for prevention of subarachnoid hemorrhage: the stage is set for a
      randomized controlled trial.

PMID- 24030179
TI  - [Dietary fiber--adequate intake and effects on metabolism health].
AB  - The positive effects of dietary fiber are related, in part, to the fact that a
      portion of the fermentation of components takes place in the large intestine,
      which has an impact on the speed of digestion, pH of the colon, and production of
      by-products with important physiological functions. Individuals with high fiber
      intake seem to have lower risk of developing coronary artery disease,
      hypertension, obesity, diabetes, and colon cancer. The increase in fiber intake
      reduces serum cholesterol, improves blood glucose in patients with diabetes,
      reduces body weight, and is associated with lower serum ultrasensitive C-reactive
      protein. Increased fiber intake and intake of more fiber than the currently
      recommended level (14 g/1,000 kcal) may provide greater health benefits,
      including reducing low-grade inflammation. 

PMID- 24030180
TI  - Diagnosis and management of primary hyperparathyroidism--a scientific statement
      from the Department of Bone Metabolism, the Brazilian Society for Endocrinology
      and Metabolism.
AB  - OBJECTIVE: To conduct a literature review on the diagnosis and management of
      primary hyperparathyroidism including the classical hipercalcemic form as well as
      the normocalcemic variant. MATERIALS AND METHODS: This scientific statement was
      generated by a request from the Brazilian Medical Association (AMB) to the
      Brazilian Society for Endocrinology as part of its Clinical Practice Guidelines
      program. Articles were identified by searching in PubMed and Cochrane databases
      as well as abstracts presented at the Endocrine Society, Brazilian Society for
      Endocrinology Annual Meetings and the American Society for Bone and Mineral
      Research Annual Meeting during the last 5 years. Grading quality of evidence and
      strength of recommendation were adapted from the first report of the Oxford
      Centre for Evidence-based Medicine. All grades of recommendation, including "D",
      are based on scientific evidence. The differences between A, B, C and D, are due
      exclusively to the methods employed in generating evidence. CONCLUSION: We
      present a scientific statement on primary hyperparathyroidism providing the level
      of evidence and the degree of recommendation regarding causes, clinical
      presentation as well as surgical and medical treatment.

PMID- 24030181
TI  - Excessive daytime sleepiness in type 2 diabetes.
AB  - OBJECTIVE: To examine excessive daytime sleepiness (EDS) in type 2 diabetes.
      SUBJECTS AND METHODS: Patients (N = 110) were evaluated regarding Epworth
      Sleepiness Scale (EDS), sleep quality (Pittsburgh Sleep Quality Index),
      depressive symptoms (Beck Depression Inventory), Restless Legs Syndrome (RLS),
      risk of obstructive sleep apnea (OSA) (Berlin questionnaire), and comorbidity
      severity (Charlson Comorbidity Index). Patients were compared with individuals
      with arterial hypertension and without diabetes. RESULTS: Diabetic patients had
      more EDS, depressive symptoms, and higher comorbidity severity than hypertensive
      patients (p < 0.005). In diabetic patients, poor quality sleep (53.3%), and high
      risk of OSA (40.9%) and RLS (14.5%) were found; EDS (55.5%) was associated with
      depressive symptoms present in 44.5% individuals (OR = 1.08; 95% CI: 1.01-1.15),
      and remained so after data were controlled for age, gender, body mass index, and
      glycated hemoglobin (OR = 2.27; 95% CI 1.03-5.03). CONCLUSIONS: Sleep
      abnormalities are frequent. EDS affects most of the patients and is independently
      associated with depressive symptoms. Adequate antidepressant therapy should be
      tested for the effects on EDS.

PMID- 24030182
TI  - Decreased astrocytic GFAP expression in streptozotocin-induced diabetes after
      gliotoxic lesion in the rat brainstem.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of diabetic
      hyperglycemia on astrocyte function, estimated by means of glial fibrillary
      acidic protein - GFAP - immunohistochemical expression. MATERIALS AND METHODS:
      Adult male rats received a single intravenous injection of streptozotocin (50
      mg/kg) and were submitted 10 days later to a single injection of 10 microlitres
      0.1% EB solution or 0.9% saline solution into the cisterna pontis. Ten
      microliters of 0.1% EB or 0.9% saline solution were also injected in non-diabetic
      rats. Animals were anesthetized and perfused through the heart 15 and 31 days
      after EB or saline injection, and brainstem sections were collected for
      ultrastructural analysis and GFAP immunohistochemical staining. RESULTS: The GFAP
      brown-stained areas were evaluated by colorimetry using a computerized image
      analysis system and the results have shown that diabetes hindered the increase of
      GFAP astrocyte expression in the EB-injected group compared to non-diabetic
      animals. However, diabetes did not affect GFAP response in the saline-injected
      group or in control animals. CONCLUSION: Streptozotocin-induced diabetic
      condition reduced astrocytic GFAP expression following gliotoxic injury.

PMID- 24030183
TI  - New insights into steroidogenesis in normo- and hyperandrogenic polycystic ovary
      syndrome patients.
AB  - OBJECTIVE: This study sought to examine corticosteroidogenic enzyme activities in
      normo- and hyperandrogenic polycystic ovary syndrome (PCOS) patients. SUBJECTS
      AND METHODS: This cohort study included 81 patients with biochemical
      hyperandrogenism and 41 patients with normal androgen levels. Enzyme activities
      were assessed according to the serum steroid product/precursor ratios at baseline
      and after adrenal stimulation. RESULTS: At baseline, in the delta 4 (Delta4)
      pathway, hyperandrogenic patients showed greater 17-hydroxylase and 17,20 lyase
      activities in converting progesterone (P4) into 17-hydroxyprogesterone (17-OHP4)
      and 17-hydroxypregnenolone (17-OHPE) into androstenedione (A) (p = 0.0005 and p =
      0.047, respectively) compared to normoandrogenic patients. In the delta 5
      (Delta5) pathway, the 17-hydroxylase and 17,20 lyase enzymes showed similar
      activities in both groups. Hyperandrogenic patients presented lower 21
      hydroxylase, lower 11beta-hydroxylase (p = 0.0001), and statistically significant
      increases in 3beta-hydroxysteroid dehydrogenase II (3beta-HSDII) activities (p <
      0.0001). Following tetracosactrin stimulation, only the 17,20 lyase activity
      remained up-regulated in the Delta4 pathway (p < 0.0001). CONCLUSION:
      Hyperandrogenic patients had higher 17,20 lyase activity, both at baseline and
      after adrenal stimulation. Greater conversion of dehydroepiandrosterone (DHEA)
      into A with normal conversion of 17-OHPE to 17-OHP4 in hyperandrogenic PCOS
      patients indicated different levels of 3beta-HSDII activity in adrenal cells, and
      hyperandrogenic patients had lower 11beta-hydroxylase and 21-hydroxylase
      activities.

PMID- 24030184
TI  - Study of the histological profile of papillary thyroid carcinomas associated with
      Hashimoto's thyroiditis.
AB  - OBJECTIVE: To investigate the association between the histological parameters of
      papillary thyroid cancer (PTC) and the presence of Hashimoto's thyroiditis (HT).
      MATERIALS AND METHODS: Histological samples from patients with PTC were reviewed
      by an endocrine pathologist. The following parameters were analyzed: presence of
      concomitant HT, multifocality, presence of nodal metastasis, tumor size, vascular
      invasion, perineural infiltration, histological variant, and pathological
      staging. Clinical data included gender and age at the time of the diagnosis.
      RESULTS: A total of 94 cases of PTC were reviewed. There was a predominance of
      women (85.1% vs. 14.9%) and median age at presentation was 45.13 years. The
      presence of HT was significantly associated with greater occurrence of multifocal
      tumors (p = 0.004), early pathological stage (p = 0.02), and smaller tumor size
      (p = 0.025). CONCLUSIONS: Patients with PTC associated with HT had significantly
      smaller tumors, more often multifocal and in an earlier stage than their
      counterparts without HT. A better understanding of the immune response involved
      in these tumors may be useful for future strategies on the prevention and for the
      development of new therapeutic approaches for this group of neoplasms.

PMID- 24030185
TI  - Evaluation of thyroid function and autoimmunity in HIV-infected women.
AB  - Autoimmune thyroid diseases (AITD) are the main causes of thyroid dysfunction and
      the most common autoimmune diseases in the world. An association between AITD and
      infections with the human immunodeficiency virus (HIV), in combination with the
      effects of highly active anti-retroviral therapy (HAART), has been suggested by
      several research groups. The aim of the present study was to evaluate the
      frequency of thyroid dysfunction and AITD in women > 35 years of age infected
      with HIV, and to identify factors associated with the emergence of these thyroid
      abnormalities. HIV-infected women (n = 153) selected from the infectious disease
      outpatient clinic at a University Hospital in Rio de Janeiro were characterized
      based on their circulating CD4+ lymphocytes levels, viral loads, serum TSH
      levels, and the presence of FT4 and anti-thyroperoxidase antibodies (TPO-Ab). A
      total of 129 participants were on HAART and 24 were not. The frequency of thyroid
      disorders was 7.8% (12/153 patients) and all were on HAART at the time of
      diagnosis, yielding a prevalence of 9.3% in patients receiving HAART compared
      with 0% in patients not on HAART. AITD, hyper, and hypothyroidism were detected
      in 4.6%, 3.1%, and 4.1% of HAART patients. It was not detected any thyroid
      dysfunction or autoimmunity in HIV-infected women not on HAART. This study
      demonstrated an association between HAART and the development of AITD. In
      addition AITD only developed in HAART patients also presenting with undetectable
      viral loads and slightly elevated CD4+ T cell counts. 

PMID- 24030186
TI  - Parameters of glycemic control in type 2 diabetic patients on hemodialysis or
      peritoneal dialysis: implications for clinical practice.
AB  - OBJECTIVE: To better explore the relationship between parameters of glycemic
      control of T2DM in RRT, we studied 23 patients on hemodialysis (HD), 22 on
      peritoneal dialysis (PD), and compared them with 24 T2DM patients with normal
      renal function (NRF). MATERIALS AND METHODS: We performed, on four consecutive
      days, 10 assessments of capillary blood glucose [4 fasting, 2 pre- and 4
      postprandial (post-G) and average (AG)], random glycemia, and HbA1c in all
      patients. RESULTS: Preprandial blood glucose was greater in patients on RRT
      compared with NRF. Correlations between AG and HbA1c were 0.76 for HD, 0.66 for
      PD, and 0.82 for NRF. The regression lines between AG and HbA1c were similar for
      patients on HD and with NFR, but they were displaced upward for PD. CONCLUSION:
      Similar HbA1c values in PD patients may correspond to greater levels of AG than
      in HD or NRF patients.

PMID- 24030187
TI  - [Association of processed meat intake and obesity in a population-based study of
      Japanese-Brazilians].
AB  - OBJECTIVE: The aim of this study was to investigate the association between the
      consumption of processed meat with overall, abdominal, and overall with abdominal
      obesity in a Japanese-Brazilian population, which is known to be at
      cardiometabolic risk. SUBJECTS AND METHODS: A total of 329 men and 443 women aged
      >= 30 years were evaluated in a cross-sectional population-based survey.
      Diagnosis of overall obesity and abdominal obesity were based on the World Health
      Organization (WHO) criteria for Asians. Food intake was assessed by a validated
      food frequency questionaire. RESULTS: In men, processed meat intake was
      positively associated with overall with abdominal obesity (OR 2.97; 95%CI 1.13
      7.78) after adjustment. In women, only the red meat group was associated with
      overall with abdominal obesity after adjustment (OR 0.47, 95%CI 0.23-0.96).
      CONCLUSION: Our results showed that high intakes of processed meats were
      associated with overall with abdominal obesity in male Japanese-Brazilians, but
      not in females.

PMID- 24030188
TI  - Iodine nutrition in elementary state schools of Queretaro, Mexico: correlations
      between urinary iodine concentration with global nutrition status and social gap
      index.
AB  - OBJECTIVE AND METHODS: To estimate median urinary iodine concentration (UIC), and
      to correlate it with global nutrition indicators and social gap index (SGI) in 50
      elementary state schools from 10 municipalities in the State of Queretaro,
      Mexico. RESULTS: 1,544 students were enrolled and an above of requirements of
      iodine intake was found (median UIC of 297 ug/L). Iodine status was found as
      deficient, adequate, more than adequate and excessive in 2, 4, 19 and 25 schools,
      respectively. Seventy seven percent of table salt samples showed adequate iodine
      content (20-40 ppm), while 9.6% of the samples had low iodine content (< 15 ppm).
      Medians of UIC per school were positively correlated with medians of body mass
      index (BMI) by using the standard deviation score (SDS) (r = 0.47; p < 0.005),
      height SDS (r = 0.41; p < 0.05), and overweight and obesity prevalence (r = 0.41;
      p < 0.05). Medians of UIC per school were negatively correlated with stunting
      prevalence (r = -0.39; p = 005) and social gap index (r = -0.36; p < 0.05). Best
      multiple regression models showed that BMI SDS and height were significantly
      related with UIC (p < 0.05). CONCLUSIONS: There is coexistence between the two
      extremes of iodine intake (insufficient and excessive). To our knowledge, the
      observed positive correlation between UIC and overweight and obesity has not been
      described before, and could be explained by the availability and consumption of
      snack food rich in energy and iodized salt.

PMID- 24030189
TI  - Horner syndrome as a manifestation of thyroid carcinoma: a rare association.
AB  - An 82-year-old patient presented a progressively growing hard thyroid nodule, and
      left ptosis. Additionally, ophthalmologic evaluation revealed ipsilateral miosis,
      diagnostic findings of Horner syndrome. Computerized tomography revealed a 7.5-cm
      thyroid mass infiltrating the main neck vessels. Although clinical and imaging
      data were suggestive of poorly differentiated thyroid carcinoma, fine-needle
      aspiration led to the diagnosis of papillary carcinoma. Paliative care was
      proposed to the patient due to the advanced stage of the neoplasm and to
      significant comorbidities. Horner syndrome is an infrequent manifestation of
      thyroid disorders and benign etiologies are more often implied. Malignant thyroid
      neoplasms represent a rare cause of Horner syndrome. However, an appropriate and
      prompt diagnosis is paramount for timely treatment of rare thyroid malignancies. 

PMID- 24030190
TI  - Spontaneous remission of hypercortisolism presumed due to asymptomatic tumor
      apoplexy in ACTH-producing pituitary macroadenoma.
AB  - Cushing's disease (CD) is usually caused by secretion of ACTH by a pituitary
      corticotroph microadenoma. Nevertheless, 7%-20% of patients present with ACTH
      secreting macroadenomas. Our aim is to report a 36-year-old female patient with
      CD due to solid-cystic ACTH-macroadenoma followed up during 34 months. The
      patient presented spontaneous remission due to presumed asymptomatic tumor
      apoplexy. She showed typical signs and symptoms of Cushing's syndrome (CS).
      Initial tests were consistent with ACTH-dependent CS: elevated urinary free
      cortisol, abnormal serum cortisol after low dose dexamethasone suppression test,
      and elevated midnight salivary cortisol, associated with high plasma ACTH levels.
      Pituitary magnetic resonance imaging (MRI) showed a sellar mass of 1.2 x 0.8 x
      0.8 cm of diameter with supra-sellar extension leading to slight chiasmatic
      impingement, and showing hyperintensity on T2-weighted imaging, suggesting a
      cystic component. She had no visual impairment. After two months, while waiting
      for pituitary surgery, she presented spontaneous resolution of CS. Tests were
      consistent with remission of hypercortisolism: normal 24-h total urinary cortisol
      and normal midnight salivary cortisol. Pituitary MRI showed shrinkage of the
      tumor with disappearance of the chiasmatic compression. She has been free from
      the disease for 28 months (without hypercortisolism or hypopituitarism). The
      hormonal and imaging data suggested that silent apoplexy of pituitary tumor led
      to spontaneous remission of CS. However, recurrence of CS was described in cases
      following pituitary apoplexy. Therefore, careful long-term follow-up is required.

PMID- 24030191
TI  - Nucleic acid recovery from thyroid fine-needle cytology slides.

PMID- 24030192
TI  - Perspectives in isolation of microRNA from thyroid fine-needle aspiration: reply
      to the letter "Nucleic acid recovery from thyroid fine-needle cytology slides".

PMID- 24030193
TI  - Is there a higher cardiovascular disease risk in Japanese-Brazilians?

PMID- 24030194
TI  - Response to the letter: Is there a higher cardiovascular disease risk in Japanese
      Brazilians?

PMID- 24030195
TI  - Detection of Onchocerca volvulus in Latin American black flies for pool screening
      PCR using high-throughput automated DNA isolation for transmission surveillance.
AB  - The posttreatment entomological surveillance (ES) of onchocerciasis in Latin
      America requires quite large numbers of flies to be examined for parasite
      infection to prove that the control strategies have worked and that the infection
      is on the path of elimination. Here, we report a high-throughput automated DNA
      isolation of Onchocerca volvulus for PCR using a major Latin American black fly
      vector of onchocerciasis. The sensitivity and relative effectiveness of silica
      coated paramagnetic beads was evaluated in comparison with phenol chloroform (PC)
      method which is known as the gold standard of DNA extraction for ES in Latin
      America. The automated method was optimized in the laboratory and validated in
      the field to detect parasite DNA in Simulium ochraceum sensu lato flies in
      comparison with PC. The optimization of the automated method showed that it is
      sensitive to detect O. volvulus with a pool size of 100 flies as compared with PC
      which utilizes 50 flies pool size. The validation of the automated method in
      comparison with PC in an endemic community showed that 5/67 and 3/134 heads pools
      were positive for the two methods, respectively. There was no statistical
      variation (P < 0.05) in the estimation of transmission indices generated by
      automated method when compared with PC method. The fact that the automated method
      is sensitive to pool size up to 100 confers advantage over PC method and can,
      therefore, be employed in large-scale ES of onchocerciasis transmission in
      endemic areas of Latin America.

PMID- 24030196
TI  - Blast-related ear injuries among U.S. military personnel.
AB  - Blast-related ear injuries are a concern during deployment because they can
      compromise a servicemember's situational awareness and adversely affect
      operational readiness. The objectives of this study were to describe blast
      related ear injuries during Operation Iraqi Freedom, identify the effect of
      hearing protection worn at the point of injury, and explore hearing loss and
      tinnitus outcomes within one year after injury. The Expeditionary Medical
      Encounter Database was used to identify military personnel who survived blast
      related injury, and it was linked with outpatient medical databases to obtain
      diagnoses of hearing loss and tinnitus. The prevalence of ear injuries was 30.7%
      (1,223 of 3,981). The most common ear injury diagnoses were "inner or middle ear
      injury involving tinnitus" and tympanic membrane (TM) rupture. Hearing protection
      reduced the odds of ear injury involving tinnitus. Personnel with TM rupture had
      higher odds of hearing loss (odds ratio [OR] = 6.65, 95% confidence interval [CI]
      = 5.04-8.78) and tinnitus outcomes (OR = 4.34, 95% CI = 3.12-6.04) than those
      without TM rupture. Ear injuries and hearing impairment are frequent consequences
      of blast exposure during combat deployment. Hearing protection is warranted for
      all servicemembers at risk of blast exposure.

PMID- 24030197
TI  - Detection of salt bridges to lysines in solution in barnase.
AB  - We show that salt bridges involving lysines can be detected by deuterium isotope
      effects on NMR chemical shifts of the sidechain amine. Lys27 in the ribonuclease
      barnase is salt bridged, and mutation of Arg69 to Lys retains a partially buried
      salt bridge. The salt bridges are functionally important. 

PMID- 24030199
TI  - Pilot study using proteomics to identify predictive biomarkers of necrotizing
      enterocolitis from buccal swabs in very low birth weight infants.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a major cause of death and
      morbidity in very low birth weight infants. OBJECTIVE: To identify biomarker(s)
      that would predict NEC using buccal swab samples utilizing a proteomic approach.
      METHODS: Cumulative buccal swab samples derived from very low birth weight
      preterm infants (<32 weeks' gestational age and <1,250 g) at 1, 2 and 3 weeks
      prior to the development of NEC and matched controls were subjected to two
      dimensional difference gel electrophoresis and LC-MS/MS analysis for proteomic
      protein discovery. After identification of 21 altered proteins, we chose 3
      candidate proteins using a broad systems biologic analysis approach that
      suggested several altered cellular processes that could be associated with NEC.
      RESULTS: Preliminary validation studies using Western blots on these samples and
      10 additional NEC and 10 matched control buccal samples collected within 2 or 3
      weeks before NEC diagnosis analysis showed lower interleukin-1 receptor
      antagonist. CONCLUSION: Our results suggest that interleukin-1 receptor
      antagonist is worthy of further studies to determine its utility in helping
      predict NEC.

PMID- 24030200
TI  - Effect of antidepressant medication use on emotional information processing in
      major depression.
AB  - OBJECTIVE: Acute administration of antidepressant medication increases emotional
      information processing for positive information in both depressed and healthy
      persons. This effect is likely relevant to the therapeutic actions of these
      medications, but it has not been studied in patients with major depressive
      disorder taking antidepressants as typically prescribed in the community. METHOD:
      The authors used eye tracking to examine the effects of antidepressant medication
      on selective attention for emotional stimuli in a sample of 47 patients with
      major depressive disorder (21 medicated and 26 unmedicated) and 47 matched
      comparison subjects without depression. Participants completed a passive-viewing
      eye-tracking task assessing selective attention for positive, dysphoric,
      threatening, and neutral stimuli in addition to providing medication information
      and self-report measures of depression and anxiety severity. RESULTS: Depressed
      participants currently taking antidepressants and nondepressed comparison
      subjects demonstrated greater total gaze duration and more fixations for positive
      stimuli compared with unmedicated depressed participants. Depressed participants
      on medication also had fewer fixations for dysphoric stimuli compared with
      depressed participants not on medication. CONCLUSIONS: Antidepressants, as
      prescribed in the community to patients with depression, appear to modify
      emotional information processing in the absence of differences in depression
      severity. These results are consistent with previous work and indicate a robust
      effect for antidepressants on positive information processing. They also provide
      further evidence for modification of information processing as a potential
      mechanism of action for antidepressant medication.

PMID- 24030201
TI  - Molecular detection assay of the bud mite Trisetacus juniperinus on Cupressus
      sempervirens in nurseries of central Italy.
AB  - Trisetacus juniperinus (Nalepa) sensu Keifer (Acari: Eriophyoidea: Phytoptidae)
      causes irregular development of buds, shoot deformations and stunted growth of
      trees, resulting in a serious threat to nurseries and young stands of Cupressus
      sempervirens L. (Mediterranean cypress). Recently, some cypress clones selected
      for their resistance to the fungal canker agent Seiridium cardinale (Wag.) have
      shown high susceptibility to the mite. Considering its tiny body, its hidden
      lifestyle inside the buds and the probable occurrence of other species (the
      vagrant Epitrimerus cupressi (Keifer) is common on the Mediterranean cypress in
      Italy), detection and monitoring of T. juniperinus require taxonomic expertise
      and are often time-consuming and challenging before serious damage is
      discernible. In the present study, a rapid, cost-effective PCR-based method was
      developed and validated to detect T. juniperinus on cypresses. The cytochrome c
      oxidase subunit I gene was amplified with degenerate and specific primers, but
      the latter were the only ones able to discriminate between T. juniperinus and E.
      cupressi. PCR products distinguished the two species both in a pool of
      individuals in a mixed population of both species and in single individuals,
      indicating the sensitivity of the detection method. PCR-RFLP (restriction
      fragment length polymorphism) by means of XmnI and XbaI endonucleases separated
      the two species. Furthermore, a washing-sieving protocol was used to make mite
      collection from the tree sample faster and simpler; this procedure did not
      interfere with the molecular detection of the species. The possibility of the
      routine use of this assay to monitor quarantine eriophyoids infesting plant
      material is discussed.

PMID- 24030202
TI  - Copper(II) and triphenylphosphine copper(I) ethylene glycol carboxylates:
      synthesis, characterisation and copper nanoparticle generation.
AB  - Ethylene glycol-functionalised copper(II) carboxylates Cu[O2CCR2(OC2H4)nOCH3]2 (n
      = 0-3; R = H, Me) (2a-e) have been prepared by the reaction of [Cu2(OAc)4.2H2O]
      with CH3O(C2H4O)nCR2CO2H (1a-e). Upon reduction of 2a-e with triphenylphosphine,
      the corresponding tris(triphenylphosphine)copper(I) complexes 3a-e were obtained,
      which could be converted to the bis(triphenylphosphine)copper(I) complexes 4a-e
      by removal of one phosphine ligand. Based on IR spectroscopy and single crystal X
      ray structure analysis the binding motif of the carboxylato group on the copper
      ion is discussed. DSC, TG and TG-MS experiments were performed to analyse the
      thermal decomposition mechanism of 2-4. Complex 4c was used as a precursor for
      the generation of copper nanoparticles by thermal decomposition in hexadecylamine
      without the need of any further reactants. Depending on the precursor
      concentration, spherical copper nanoparticles with a mean diameter ranging from
      10 to 85 nm as well as nanorods with a length of up to 1.3 MUm (aspect ratios
      ranging between 2 and 32) were obtained. Electron diffraction analysis of the
      rods suggested that they consist of five domains which are arranged around a
      fivefold rotational axis.

PMID- 24030203
TI  - Activation of the central nervous system induced by micro-magnetic stimulation.
AB  - Electrical and transcranial magnetic stimulations have proven to be
      therapeutically beneficial for patients suffering from neurological disorders.
      Moreover, these stimulation technologies have provided invaluable tools for
      investigating nervous system functions. Despite this success, these technologies
      have technical and practical limitations impeding the maximization of their full
      clinical and preclinical potential. Recently, micro-magnetic stimulation, which
      may offer advantages over electrical and transcranial magnetic stimulation, has
      proven effective in activating the neuronal circuitry of the retina in vitro.
      Here we demonstrate that this technology is also capable of activating neuronal
      circuitry on a systems level using an in vivo preparation. Specifically, the
      application of micro-magnetic fields to the dorsal cochlear nucleus activates
      inferior colliculus neurons. Additionally, we demonstrate the efficacy and
      characteristics of activation using different magnetic stimulation parameters.
      These findings provide a rationale for further exploration of micro-magnetic
      stimulation as a prospective tool for clinical and preclinical applications. 

PMID- 24030206
TI  - Relationship between cyclophilin a levels and matrix metalloproteinase 9 activity
      in cerebrospinal fluid of cognitively normal apolipoprotein e4 carriers and blood
      brain barrier breakdown.

PMID- 24030207
TI  - Should CLIPPERS be considered a Prelymphoma state or a new Inflammatory disease?

PMID- 24030209
TI  - Should CLIPPERS be considered a Prelymphoma state or a new Inflammatory disease.

PMID- 24030210
TI  - Oral contrast enhances the resolution of in-life NIS reporter gene imaging.
AB  - Sodium iodide symporter (NIS) reporter gene imaging is an excellent technology
      for noninvasive cell fate determination in living animals unless the NIS
      transduced cells reside in perigastric organs such as the spleen, liver,
      diaphragm, omentum, pancreas, perigastric lymph nodes or perigastric tumor
      deposits. Here we report that orally administered barium sulfate enhances CT
      definition of the stomach, masks background gamma ray emissions from the stomach
      and enhances signal detection from radiotracer uptake in NIS-transduced organs.

PMID- 24030212
TI  - Quality of professional players' poker hands is perceived accurately from arm
      motions.

PMID- 24030211
TI  - Overcoming cancer cell resistance to VSV oncolysis with JAK1/2 inhibitors.
AB  - Oncolytic vesicular stomatitis virus (VSV) has potent antitumor activity but some
      cancer cells are resistant to VSV killing, either constitutively or due to type I
      interferon (IFN) inducing an antiviral state in the cells. Here, we evaluated VSV
      oncolysis of a panel of human head and neck cancer cells and showed that VSV
      resistance in SCC25 and SCC15 cells could be reversed with Janus kinase (JAK) 1/2
      inhibitors (JAK inhibitor I and ruxolitinib). Pre-treatment of cells with JAK1/2
      inhibitors before or in conjunction with VSV enhanced viral infection, spread and
      progeny yield (100- to 1000-fold increase). In contrast, inhibitors of histone
      deacetylase (LBH589), phosphatidylinositol 3-kinase (GDC-0941, LY294002),
      mammalian target of rapamycin (rapamycin) or signal transducer and activator of
      transcription 3 (STAT3 inhibitor VII) were ineffective. Compared with VSV
      sensitive SW579 cells, IFNalpha/beta responsive antiviral genes (IRF-9, IRF-7,
      OAS1 but not MxA) are constitutively expressed in SCC25 cells. Pretreatment with
      JAK inhibitors reduced mRNA levels of these genes, increasing VSV expression in
      the cells. Interestingly, 1 h of drug exposure was sufficient to reverse SCC25
      resistance to VSV and was still effective if virus was added 24 h later. Overall,
      we show here that JAK inhibitor I and ruxolitinib (Jakafi) can reverse resistance
      to VSV, supporting the rationale to incorporate JAK1/2 inhibitors in future VSV
      virotherapy trials.

PMID- 24030214
TI  - Urethrovaginal fistulae associated with tension-free vaginal tape procedures: a
      clinical challenge.
AB  - Seven women with urethrovaginal fistulae and penetration of tension-free vaginal
      tape into the urethra were treated at our department between July 2007 and March
      2013. Fistulae were diagnosed 1 month to 10 years after midurethral sling
      placement. All were managed surgically. Five patients developed recurrent
      postoperative stress urinary incontinence, which was treated conservatively in
      all cases. In three cases, additional surgical treatment using a midurethral
      sling was performed. 

PMID- 24030213
TI  - Epigenetic landscape of Parkinson's disease: emerging role in disease mechanisms
      and therapeutic modalities.
AB  - Parkinson's disease (PD) is a complex multifactorial disorder marked by extensive
      system-wide pathology, including a substantial loss of nigrostriatal dopaminergic
      neurons. The etiology of PD remains elusive, but there is considerable evidence
      that, in addition to well-defined genetic mechanisms environmental factors play a
      crucial role in disease pathogenesis. How the environment might influence the
      genetic factors and contribute to disease development and progression remains
      unclear. In recent years, epigenetic mechanisms such as DNA methylation,
      chromatin remodeling and alterations in gene expression via non-coding RNAs have
      begun to be revealed as potential factors in PD pathogenesis. Epigenetic
      modulation exists throughout life, beginning in prenatal stages, is dependent on
      the lifestyle, environmental exposure and genetic makeup of an individual and may
      serve as a missing link between PD risk factors and development of the disease.
      This chapter sheds light on the emerging role of epigenetics in disease
      pathogenesis and on prospective interventional strategies for the therapeutic
      modulation of PD. 

PMID- 24030215
TI  - Reasons for dissatisfaction ten years after TVT procedure.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of the study was to assess the reasons for
      dissatisfaction 10 years after TVT placement. METHODS: Patients who underwent TVT
      surgery between 1999 and 2001 at two participating units were included. All
      patients who did not consider themselves to be cured were asked for their
      reasons. RESULTS: 141 out of 210 patients (81 %) were available for follow-up
      (median 116 months). In the group of 56 patients who did not consider themselves
      cured, the reasons were OAB symptoms in 29 patients (52 %), stress urinary
      incontinence in 13 patients (23 %), and complaints of mixed urinary incontinence
      in 8 patients (14 %). 85 % of all patients reporting urgency complaints at the
      time of follow-up and 66 % of patients with SUI at the time of follow-up did not
      consider themselves cured. CONCLUSIONS: In most cases overactive bladder symptoms
      were the reason for dissatisfaction. The results of this study support using
      composite outcomes to assess the results of surgery for urinary incontinence.

PMID- 24030216
TI  - Iliococcygeus fixation or abdominal sacral colpopexy for the treatment of vaginal
      vault prolapse: a retrospective cohort study.
AB  - INTRODUCTION AND HYPOTHESIS: To compare the efficacy and safety of iliococcygeus
      fixation (ICG) and abdominal sacral colpopexy (SCP) in the treatment of vaginal
      vault prolapse. METHODS: Patients with symptomatic vaginal vault prolapse after
      hysterectomy were considered in this analysis. Surgical outcomes, i.e., the
      capacity to restore the anatomy of the vaginal cuff and improvement in the
      prolapse-related symptoms were compared. Continuous variables were compared using
      the Student's t test, while non-continuous variables using a Chi-squared test or
      Fisher's exact test. RESULTS: Sacrocolpopexy was performed in 41 patients, while
      ICG fixation was carried out in 36 patients. Operative time was significantly
      shorter (78 vs 140 min, p < 0.001) and median blood loss higher in the ICG group
      (150 ml vs 100 ml, p=0.01). The rates of postoperative complications of the two
      groups were not statistically different. Relapse rate was similar in the two
      groups (15 % in the SCP and 22 % in the ICG group respectively, p=0.36).
      Considering the POP-Q score, both SCP and ICG achieved a significant and
      comparable correction of vaginal prolapse. The evaluation of postoperative
      subjective symptoms revealed a significant improvement in voiding and vaginal
      bulging related to pelvic organ prolapse in both groups. CONCLUSIONS: Both ICG
      fixation and SCP are effective in restoring normal anatomy in patients with
      vaginal vault prolapse and in relieving associated symptoms. Owing to its lower
      morbidity and to the advantage of not using a synthetic device, ICG might be an
      excellent option for the treatment of recurrent vaginal vault prolapse following
      hysterectomy.

PMID- 24030218
TI  - It's decision time!

PMID- 24030217
TI  - Severe adolescent female stress urinary incontinence (SAFSUI): case report and
      literature review.
AB  - INTRODUCTION: Severe adolescent female stress urinary incontinence (SAFSUI) can
      be defined as female adolescents between the ages of 12 and 17 years complaining
      of involuntary loss of urine multiple times each day during normal activities or
      sneezing or coughing rather than during sporting activities. An updated review of
      its likely prevalence, etiology, and management is required. MATERIALS AND
      METHODS: The case of a 15-year-old female adolescent presenting with a 7-year
      history of SUI resistant to antimuscarinic medications and 18 months of intensive
      physiotherapy prompted this review. Issues of performing physical and urodynamic
      assessment at this young age were overcome in order to achieve the diagnosis of
      urodynamic stress incontinence (USI). Failed use of tampons was followed by the
      insertion of (retropubic) suburethral synthetic tape (SUST) under assisted local
      anesthetic into tissues deemed softer than the equivalent for an adult female.
      RESULTS: Whereas occasional urinary incontinence can occur in between 6 % and 45
      % nulliparous adolescents, the prevalence of non-neurogenic SAFSUI is uncertain
      but more likely rare. Risk factors for the occurrence of more severe AFSUI
      include obesity, athletic activities or high-impact training, and lung diseases
      such as cystic fibrosis (CF). This first reported use of a SUST in a patient with
      SAFSUI proved safe and completely curative. Artificial urinary sphincters,
      periurethral injectables and pubovaginal slings have been tried previously in
      equivalent patients. CONCLUSIONS: SAFSUI is a relatively rare but physically and
      emotionally disabling presentation. Multiple conservative options may fail,
      necessitating surgical management; SUST can prove safe and effective.

PMID- 24030219
TI  - QI: nursing's "evolving responsibility".

PMID- 24030220
TI  - Bis-naphthobipyrrolylmethene derived BODIPY complex: an intense near-infrared
      fluorescent dye.
AB  - Synthesis of a novel pi-extended BODIPY derived from naphthobipyrrole is
      presented. This dye molecule displays very intense near-infrared (NIR) absorption
      (epsilon > 400,000 M(-1) cm(-1)) and emission bands (>700 nm), accompanied by
      high quantum yield (phif = 0.65) owing to its extended pi-conjugation along with
      imposed structural rigidification.

PMID- 24030222
TI  - Inflammatory bowel disease (IBD). Preface.

PMID- 24030221
TI  - Passive smoking impairs histone deacetylase-2 in children with severe asthma.
AB  - BACKGROUND: Parental smoking is known to worsen asthma symptoms in children and
      to make them refractory to asthma treatment, but the molecular mechanism is
      unclear. Oxidative stress from tobacco smoke has been reported to impair histone
      deacetylase-2 (HDAC2) via phosphoinositide-3-kinase (PI3K)/Akt activation and,
      thus, to reduce corticosteroid sensitivity. The aim of this study was to
      investigate passive smoking-dependent molecular abnormalities in alveolar
      macrophages (AMs) by comparing passive smoke-exposed children and non-passive
      smoke-exposed children with uncontrolled severe asthma. METHODS: BAL fluid (BALF)
      was obtained from 19 children with uncontrolled severe asthma (10 non-passive
      smoking-exposed subjects and nine passive smoking-exposed subjects), and HDAC2
      expression/activity, Akt/HDAC2 phosphorylation levels, and corticosteroid
      responsiveness in AMs were evaluated. RESULTS: Parental smoking reduced HDAC2
      protein expression by 54% and activity by 47%, with concomitant enhancement of
      phosphorylation of Akt1 and HDAC2. In addition, phosphorylation levels of Akt1
      correlated positively with HDAC2 phosphorylation levels and negatively with HDAC2
      activity. Furthermore, passive smoke exposure reduced the inhibitory effects of
      dexamethasone on tumor necrosis factor-alpha-induced CXCL8 release in AMs. There
      were relatively higher neutrophil counts and CXCL8 concentrations in BALF and
      lower Asthma Control Test scores compared with non-passive smoke-exposed children
      with uncontrolled severe asthma. CONCLUSIONS: Passive smoking impairs HDAC2
      function via PI3K signaling activation, which could contribute to corticosteroid
      insensitive inflammation in children with severe asthma. This novel mechanism
      will be a treatment target in children with severe asthma and stresses the need
      for a smoke-free environment for asthmatic children.

PMID- 24030223
TI  - Mechanisms of tissue remodeling in inflammatory bowel disease.
AB  - The clinical course of inflammatory bowel disease (IBD) is highly heterogeneous
      and often unpredictable, with multiple and serious complications that range from
      stricture formation to bowel obstruction or perforation, fistula formation and
      the need for surgery. All these problems are manifestations of tissue remodeling,
      a secondary but universal response to the insults of chronic inflammation. The
      factors involved in tissue remodeling are several, including the site and
      duration of inflammation, soluble molecules, the gut microbiota, and the type of
      mesenchymal cell response. The prototypical and most common type of tissue
      remodeling in IBD, and Crohn's disease (CD) in particular, is a fibrotic
      response, and this review will focus on the factors and mechanisms involved in
      fibrogenesis, and speculate on what is needed for the development of a rational
      treatment of intestinal fibrosis.

PMID- 24030224
TI  - Endoscopic assessment of the small bowel.
AB  - BACKGROUND: Small bowel imaging and endoscopy in IBD have undergone a tremendous
      change and advancement in the recent years. Modalities shifted from gastroscopy,
      colonoscopy and small bowel follow through to ileocolonoscopy, CT or MR
      enteroscopy, wireless video capsule endoscopy and balloon-assisted enteroscopy.
      METHODS: We reviewed the present role of endoscopy in assessing the small bowel
      in the context of IBD. RESULTS: Endoscopy has a major role in the diagnosis of
      IBD, in the assessment of its extent, treatment of complications, assessment of
      the success of various medications and as a predictor of disease course. Wireless
      capsule endoscopy (WCE) is a relatively new tool allowing direct, patient
      friendly visualization of the entire small bowel mucosa. It has gained a
      substantial role in the evaluation of patients with suspected Crohn's disease
      (CD) and indeterminate colitis. WCE has a high positive predictive value in
      patients with suspected CD, when one uses more than two of the International
      Conference on Capsule Endoscopy criteria, and not less important a very high
      negative predictive value in patients with suspected CD. Its role in patients
      with known CD, in the assessment of their disease activity and extent, assessment
      of postsurgical small bowel recurrence and evaluation of mucosal healing is still
      unclear. Balloon-assisted enteroscopy has established its role as a complementary
      tool in cases where there is a need for biopsy or treatment (dilatation of
      strictures). CONCLUSIONS: The present review summarizes the role of endoscopy in
      the assessment of the small bowel in the context of IBD.

PMID- 24030225
TI  - Cross-sectional imaging modalities in Crohn's disease.
AB  - The standard tools assessing the activity of Crohn's disease (CD) measure the
      severity of symptoms (the Crohn's Disease Activity Index) or the degree of
      endoscopic lesions (the Crohn's Disease Endoscopic Index of Severity, the
      Simplified Endoscopy Score), not the global bowel damage. It is necessary to find
      new instruments able to assess the structural and functional damage to the
      intestine and the progression over time. We reviewed recent publications on the
      accuracy of abdominal ultrasound (US), computed tomography enterography (CTE),
      and magnetic resonance imaging enterography (MRE) for the assessment of CD. US,
      CTE and MRE have been shown to have a high and comparable diagnostic accuracy for
      both the diagnosis and complications of CD, but US and MRE have the major
      advantage of not imparting ionizing radiation. In summary, findings from these
      imaging modalities with endoscopic lesions and surgical history incorporating
      into the Lemann score will allow measuring the global bowel damage at specific
      time and the progression of disease over time and assessing the impact of
      different strategies.

PMID- 24030226
TI  - Challenging question: can we diagnose Crohn's disease without histology?
AB  - No single test is diagnostic of Crohn's disease (CD). In the presence of a
      compatible clinical presentation, diagnosis is by convention confirmed by a
      combination of imaging, serologic, endoscopic and histologic investigations. This
      diagnostic recommendation should be maintained, even though histology is often
      'compatible with' rather than 'diagnostic of' suspected CD. The importance of
      histology varies depending on the specific sites of macroscopic disease.
      Histology is particularly important in distinguishing type of inflammatory bowel
      disease, when the colon predominantly is involved, and in confirming CD when
      macroscopic disease is atypically located.

PMID- 24030227
TI  - Strategic use of immunosuppressants and anti-TNF in inflammatory bowel disease.
AB  - Controlled trials and meta-analyses have shown that immunosuppressants are
      effective in steroid-dependent Crohn's disease (CD) and, although less well
      demonstrated, ulcerative colitis (UC). It has also been demonstrated that anti
      TNF are effective in steroid-dependent and steroid-refractory CD and UC. Anti-TNF
      can also decrease hospitalization rate and the need for surgery. This seems also
      to be the case for immunosuppressants. The early use of anti-TNF seems more
      effective than later use, and early mucosal healing is associated with decreased
      rate of surgery. On the contrary, early use of purine analogues does not seem to
      improve outcome in CD. Anti-TNF therapies have been shown superior to
      immunosuppressants and combination therapy superior to anti-TNF monotherapy in
      inducing steroid-free remission and mucosal healing. The main strategic questions
      which remain at this stage include: When to start immunosuppressants or anti-TNF?
      Is there still a place for immunosuppressant monotherapy? How to optimize anti
      TNF? Is it possible to stop anti-TNF? The main justification of immunosuppressant
      monotherapy is the low cost of this treatment and the possibility of achieving a
      very stable and long-standing remission in a subset of patients. According to
      this and provided there is no rapid need for more effective therapy, this
      treatment could be tried in any inflammatory bowel disease patient not correctly
      maintained after a course of steroids and 5-aminosalicylic acid. However, the
      failure to respond to this treatment should be recognized early and a step up to
      anti-TNF considered. An anti-TNF treatment should be considered early in patients
      at risk of rapid evolution towards tissue damage and complications. The
      benefit/risk of the immunosuppressant + anti-TNF combination therapy should be
      assessed on a case-by-case basis. Anti-TNF treatment should always be fully
      optimized by adapting dosage and potentially adding an immunosuppressant before
      considering treatment failure. Treatment de-escalation should only be considered
      when a long-standing stable remission has been achieved both clinically and
      biologically. The cost sparing and theoretical decrease in complication risk
      should be put in perspective with the risk of relapse and disease progression.

PMID- 24030228
TI  - Challenging question: is treating inflammatory bowel disease an art or strictly
      an evidence-based matter?
AB  - Although evidence-based medicine (EBM) is the gold standard for clinical
      practice, misconceptions among health care providers regarding EBM are common.
      The medical management of inflammatory bowel diseases (IBD) has advanced
      substantially over the last 20 years as a direct result of the wealth of new
      evidence generated by randomized controlled trials. Integrating EBM and
      traditional clinical skills results in optimal care tailored to the individual
      patient. This article addresses the role of EBM in the management of IBD and
      dispels some of the common misconceptions about the use of EBM in practice.

PMID- 24030229
TI  - Perforating Crohn's disease: conservative and surgical treatment.
AB  - Surgery is a part of the clinical history of patients with Crohn's disease (CD)
      since nearly all the patients receive at least one surgical procedure. The main
      indication for surgery is obstruction, but 50-60% of patients present a
      concomitant perforating disease at surgery, and 10% of patients have a primary
      indication for abscess or fistula. Generally, fistulas are classified on an
      anatomical basis, indicating the site of origin followed by the target (i.e.
      ileocolic, ileovesical, etc.). Enteroenteric fistulas are frequently asymptomatic
      and are not always considered an indication for surgery. However, in case of
      bypass with severe malnutrition or bacterial overgrowth (i.e. duodenal
      involvement), surgery is the only option. Enterovesical, enteroureteral and
      enterobiliary fistulas, due to their potential for septic complications, are a
      definite indication for surgery. Enterogenital fistulas have an indication mainly
      for their impact on the quality of life. Enterocutaneous fistulas are, in most
      cases, a late surgical complication, and the indication and timing for treatment
      are due to their output volume. Abscesses may be present alone or in association
      with enteric fistulas. The initial approach is conservative, and a percutaneous
      drainage should be a good treatment or a bridge to elective surgery. Since a
      modern surgical approach to CD has to be minimally invasive and highly
      conservative whenever possible, the presence of perforating disease should be
      well characterized in order to plan a laparoscopic approach and to reduce the
      amount of resected bowel, in case combining resection and strictureplasty.
      Perforating CD necessitates a multidisciplinary approach involving, behind the
      gastroenterologist and the surgeon, the radiologist, the urologist, the
      gynecologist and the nutritionist in order to obtain the best tailored treatment.

PMID- 24030230
TI  - Management of postoperative recurrence of Crohn's disease.
AB  - The course of Crohn's disease (CD) is unpredictable and potentially destructive.
      The percentage of patients requiring surgery at some stage in their disease
      accumulates to over 70%. After resection of the affected intestine, reappearance
      of CD occurs in the majority of patients. Prophylactic medical therapy to reduce
      the rate of postoperative recurrence has been proven to be effective, yet the
      incidence of recurrence remains high. Patient profiling (risk stratification) is
      important in this postoperative setting. High-risk patients (associated with e.g.
      smoking, the need of repetitive surgery and penetrating disease) require strong
      immunosuppressive treatment, which should be commenced immediately after surgery,
      when recurrent disease activity begins. Additionally, early screening endoscopy
      should be performed to monitor treatment effect. The efficacy of thiopurines is
      shown to be higher than mesalazine or imidazole antibiotics alone for preventing
      and ameliorating endoscopic recurrence of CD postoperatively; however, anti-tumor
      necrosis factors (anti-TNFs) are increasingly considered the most potent agents.
      In patients with a risk factor for early postoperative recurrence, the first line
      of treatment is 6-mercaptopurine, in combination with imidazole antibiotics if
      tolerated, followed by anti-TNFs. When lesions are found at colonoscopy, therapy
      should be upscaled. We propose a treatment algorithm to direct therapeutic
      management of CD postoperatively.

PMID- 24030231
TI  - Managing IBD outside the gut: ocular manifestations.
AB  - Extraintestinal manifestations are common in inflammatory bowel disease (IBD),
      being reported in over 25% of patients. Ocular complications of IBD occur in
      around 10% of cases, but may precede systemic symptoms and are usually
      nonspecific. Complications of therapy, such as cataracts or glaucoma from steroid
      use or keratoconjunctivitis sicca related to 5-aminosalicylic acid medications,
      may also involve the eyes. The pathogenesis remains unclear, but factors such as
      the extent of intestinal disease, disease activity, and the presence of
      associated arthritis have been associated with ocular involvement.
      Conjunctivitis, episcleritis, scleritis and uveitis are by far the most common
      ophthalmic complications of IBD. However, posterior uveitis, intraretinal
      hemorrhages, vasculitis, choroiditis, optic neuropathy, and vaso-occlusive
      phenomena may also occur. The most frequent severe ocular manifestation is
      anterior uveitis (more common in women). It usually presents as a mild anterior
      nongranulomatous uveitis (60% of the cases). The inflammation in the eye and the
      inflammation in the gut are rarely correlated. Patients with uveitis, scleritis,
      and other anterior segment inflammation usually respond to steroids (topical,
      periocular or systemic). If the inflammation is resistant to steroids, or if
      appreciable steroid adverse effects are encountered, systemic immunosuppressive
      treatment should be considered; this is more likely in HLA-B27-positive patients
      with uveitis. Evaluation of the eye should be a routine component in the care of
      patients with IBD.

PMID- 24030232
TI  - Liver complications in inflammatory bowel diseases.
AB  - Diseases of the liver and the biliary tract are commonly observed in patients
      with inflammatory bowel diseases (IBD). Besides primary sclerosing cholangitis
      (PSC), drug-induced hepatotoxicity and non-alcoholic fatty liver disease (NAFLD)
      are the most frequent liver complications in IBD. PSC is a chronic inflammatory
      and commonly progressive disorder of unknown etiology associated with fibrosis
      and stricture development in the intrahepatic and extrahepatic biliary tree.
      Interestingly, this form of liver disease is mainly associated with ulcerative
      colitis. Development of PSC is highly relevant for IBD patients as cholestasis
      associated problems increase over time resulting in biliary strictures,
      cholangitis, cholangiocarcinoma and importantly these patients also have a higher
      risk to develop colon cancer. Another major aspect regarding IBD and liver
      disease refers to drug-induced hepatotoxicity. Clinically, most relevant is liver
      toxicity caused by immunosuppressants such as azathioprine. Azathioprine and its
      derivate 6-mercaptopurine can cause a spectrum of liver injuries ranging from
      asymptomatic elevated liver enzymes to cholestasis and nodular regenerative
      hyperplasia. The third common IBD-associated liver disease is NAFLD, and first
      studies suggest that NAFLD might appear in IBD patients independent of classical
      risk factors such as obesity or insulin resistance. Overall, liver complications
      are observed in 10-20% of IBD patients, and therefore physicians have to be
      familiar with these complications to improve and to optimize patient care.

PMID- 24030233
TI  - Osteoarticular manifestations: specific treatments and/or treating intestinal
      disease?
AB  - Osteoarticular manifestations in inflammatory bowel diseases (IBD) belong to the
      concept of spondyloarthritis (SpA) including an axial and peripheral SpA
      according to predominant symptoms (inflammatory back pain vs. peripheral
      arthritis and enthesopathy). Careful examination of sacroiliac joints on MRI
      plays a crucial role in the recognition of an early axial SpA in young patients
      with inflammatory back pain and spinal inflammation on MRI but without structural
      changes on radiography (non-rx SpA). In this early form of SpA, chronic gut
      inflammation was already found in about 30% of patients. Moreover, more
      pronounced bone marrow edema was found in patients with axial SpA and chronic gut
      inflammation. Identification of a therapeutic window in patients with early gut
      and spine inflammation is important since anti-TNF suppresses inflammation and
      seems to prevent evolution to structural changes. Shared genetic factors probably
      predispose to both diseases. Careful analysis of the effect of medication on gut
      and spine inflammation in SpA and IBD patients is recommended in order to find
      new therapeutic agents.

PMID- 24030234
TI  - Overcoming challenges in IBD management: management of colonic dysplastic
      lesions.
AB  - The aim of any screening or surveillance program must be to identify early
      lesions to enable treatment and prevention before the development of invasive
      cancer. A surveillance program must be acceptable to patients and practically
      possible to implement. There is a move away from using random colonic biopsies
      towards targeted biopsies aimed at abnormal areas identified by newer
      colonoscopic techniques (narrow band imaging, chromoendoscopy, confocal
      microendoscopy). However, the attitude towards a patient with a dysplastic lesion
      is not well established. Bowel cancer screening in the general population relies
      on identification of adenomatous lesions which can be resected before they
      transform into carcinoma. The therapeutic approach to such lesions, the patient
      groups at risk and the intervals of surveillance are reasonably established. In
      contrast, inflammatory bowel disease (IBD)-colorectal cancer (CRC) poses
      different challenges: dysplastic lesions do not follow the adenoma-carcinoma
      sequence, they can be difficult to see (flat lesions), difficult to resect
      completely, and multifocal. Prophylactic proctocolectomy eliminates the risk of
      CRC, but this strategy is not acceptable to most patients or physicians.
      Moreover, IBD patients can harbor dysplastic lesions related to the sporadic CRC
      pathway, the clinical significance of which differs clearly from colitis
      associated dysplastic lesions. Nowadays, therapeutic recommendations for the
      management of dysplasia in IBD are based on macroscopic pattern and microscopic
      characteristics. As an example, consensus guidelines state that adenoma-like
      lesions can be adequately treated by polypectomy unlike non-adenoma-like raised
      lesions or flat high-grade dysplasia that should undergo colectomy. The present
      article is aimed to summarize the existing evidence on this thorny matter.

PMID- 24030235
TI  - 5-Aminosalicylic acid and chemoprevention: does it work?
AB  - 5-Aminosalicylic acid (5-ASA)-containing drugs are the mainstay of therapy in
      inflammatory bowel disease (IBD). Intestinal inflammation is the main risk factor
      for colorectal cancer (CRC) in IBD. Hence, all drugs that are able to induce and
      maintain mucosal healing (MH) may prevent CRC risk in IBD. In patients with mild
      to moderate ulcerative colitis (UC), a recent systematic review of 5-ASA trials
      demonstrated that MH was achieved in nearly 50% of patients. A systematic review
      including 48 studies linked 5-ASA chemopreventive properties to five distinct
      pathways: cell cycle progression, scavenging of reactive oxygen- or nitrogen
      derived metabolites, TNF-alpha/TGF-ss signaling, WNT/beta-catenin signaling and
      antibacterial properties. Therefore, in addition to their overall anti
      inflammatory activity on the intestinal mucosa, 5-ASA compounds have specific
      effects on colorectal carcinogenesis at the molecular level. In 2005, a landmark
      meta-analysis of observational studies found a protective association between 5
      ASA and CRC or a combined end point of CRC/dysplasia in UC patients. More
      recently, a meta-analysis failed to identify a protective effect of 5-ASA on CRC
      risk in non-referral populations, but in a separate analysis of 9 clinic-based
      studies, the pooled odds ratio was 0.58 (95% confidence interval: 0.45-0.75),
      further highlighting the chemopreventive effect of 5-ASA on CRC risk. In
      conclusion, 5-ASA therapy may reduce CRC risk by healing the mucosa of UC
      patients and via specific mechanisms of action at the molecular level. Conducting
      a clinical trial providing the best level of evidence by comparing UC patients
      receiving 5-ASA treatment versus those included in a placebo arm would be
      unethical.

PMID- 24030236
TI  - Use of immunosuppressants and biologicals in patients with previous cancer.
AB  - Thiopurines promote Epstein-Barr virus-related lymphomas, nonmelanoma skin
      cancers and acute myeloid leukemias. Anti-tumor necrosis factor (anti-TNF) agents
      may inhibit or activate carcinogenesis according to the cellular pathways that
      are activated. A mild increase in the risk of melanoma has been reported in
      patients exposed to anti-TNF agents. Transplanted patients with previous history
      of cancer are at high risk of cancer recurrence when receiving posttransplant
      immunosuppressive therapy, particularly within the first 2 years of treatment.
      Few data exist for patients with chronic inflammatory disease. In the CESAME
      cohort that included essentially patients receiving thiopurines, there was no
      excess incidence of recurrent or new cancer associated with exposure to
      immunosuppressive therapy in the patients with previous cancer at cohort entry.
      In clinical practice, the decision to start or resume immunosuppressive therapy
      in inflammatory bowel disease (IBD) patients with recent cancer should be
      discussed case by case with cancer specialists. However, taken into account the
      experience of transplant specialists, it could be suggested not to consider a
      waiting period for women with adequately treated uterine high-grade cervical
      dysplasia. For invasive cancers, a waiting period of 2 years should be considered
      if possible. During this period, treatment of IBD should be restricted to 5
      aminosalicylic acid, steroids, nutritional therapy, or surgery, except in case of
      aggressive IBD that cannot be controlled by these methods. A longer waiting
      period of 5 years could be recommended for the most aggressive forms of cancers,
      such as melanomas, aggressive breast cancers, sarcomas, urinary tract cancers,
      and myelomas.

PMID- 24030239
TI  - An infant with recurrent convulsive seizures of 3 weeks duration: questions.

PMID- 24030238
TI  - Multicomponent exercises including muscle power training enhance muscle mass,
      power output, and functional outcomes in institutionalized frail nonagenarians.
AB  - This randomized controlled trial examined the effects of multicomponent training
      on muscle power output, muscle mass, and muscle tissue attenuation; the risk of
      falls; and functional outcomes in frail nonagenarians. Twenty-four elderly (91.9
      +/- 4.1 years old) were randomized into intervention or control group. The
      intervention group performed a twice-weekly, 12-week multicomponent exercise
      program composed of muscle power training (8-10 repetitions, 40-60 % of the one
      repetition maximum) combined with balance and gait retraining. Strength and power
      tests were performed on the upper and lower limbs. Gait velocity was assessed
      using the 5-m habitual gait and the time-up-and-go (TUG) tests with and without
      dual-task performance. Balance was assessed using the FICSIT-4 tests. The ability
      to rise from a chair test was assessed, and data on the incidence and risk of
      falls were assessed using questionnaires. Functional status was assessed before
      measurements with the Barthel Index. Midthigh lower extremity muscle mass and
      muscle fat infiltration were assessed using computed tomography. The intervention
      group showed significantly improved TUG with single and dual tasks, rise from a
      chair and balance performance (P < 0.01), and a reduced incidence of falls. In
      addition, the intervention group showed enhanced muscle power and strength (P <
      0.01). Moreover, there were significant increases in the total and high-density
      muscle cross-sectional area in the intervention group. The control group
      significantly reduced strength and functional outcomes. Routine multicomponent
      exercise intervention should be prescribed to nonagenarians because overall
      physical outcomes are improved in this population. 

PMID- 24030241
TI  - Ocular manifestations of emerging infectious diseases.
AB  - PURPOSE OF REVIEW: Emergent and resurgent infectious diseases are major causes of
      systemic morbidity and death that are expanding worldwide mainly because of
      climate changes and globalization. Among them, specific diseases have been
      recently associated with ocular involvement. This review presents the ocular
      manifestations of selected emerging infectious diseases relevant to the
      ophthalmologist. RECENT FINDINGS: An array of ocular manifestations, involving
      mainly the posterior segment, have been recently described in association with
      specific arthropod vector-borne diseases including rickettsioses, West Nile
      virus, Rift Valley fever, Dengue fever, and Chikungunya. Influenza A (H1N1) virus
      has also been recently associated with ocular involvement. On the contrary, with
      advances in laboratory testing applied to ocular fluids, new infectious agents,
      mainly viruses, are increasingly being found to be associated with uveitis.
      SUMMARY: Emerging infectious diseases should be considered in the differential
      diagnosis of retinitis, chorioretinitis, retinal vasculitis, optic neuropathy, or
      any other ocular inflammatory condition in a patient living in or traveling back
      from a specific endemic area. On the contrary, ocular fluid sampling and analysis
      for specific new pathogens can be recommended in selected patients with uveitis
      of unexplained cause.

PMID- 24030243
TI  - Expression and function of vascular endothelial growth inhibitor in aged porcine
      bladder detrusor muscle cells.
AB  - Aging of the bladder detrusor muscle plays an important role in lower urinary
      tract symptoms in elderly people. Our previous work demonstrated that elderly
      patients have increased levels of vascular endothelial growth inhibitor (VEGI) in
      bladder tissue. Therefore, we hypothesized that VEGI may play a role in aging of
      the bladder detrusor muscle cells. This study aims to develop and characterize
      primary cultures of aged porcine bladder detrusor muscle cells in order to
      explore the expression and function of VEGI. Bladder samples from female pigs
      were divided into two groups: the aged group (Model) and the young group
      (Control). We confirmed beta-galactosidase expression, a marker for senescence,
      in aged muscle cells (identified by alpha-smooth muscle actin (alpha-SMA)
      staining), but not in the young group. mRNA levels of VEGI-251 and death receptor
      3 (DR3) were up-regulated (P < 0.05) and total cell protein levels of VEGI-251,
      DR3 and nuclear factor-kappa B [NF-kappaB (p65)], membrane protein levels of DR3,
      and nuclear protein levels of NF-kappaB (p65) were significantly higher (P <
      0.01) in the Model cells compared to Control cells. In conclusion, we have
      established a method to culture aged detrusor muscle cells derived from porcine
      bladder. Higher levels of VEGI-251, DR3 and NF-kappaB (p65) were observed in the
      aged cells. VEGI-251 may function by increasing DR3 on cellular membranes and
      promoting the transfer of NF-kappaB into the nucleus. This suggests that VEGI may
      be a target for reversing the aging process of bladder detrusor muscle cells. 

PMID- 24030242
TI  - Decline in muscle strength and running endurance in klotho deficient C57BL/6
      mice.
AB  - Alpha klotho (known as klotho) is a multifunctional protein that may be linked to
      age-associated decline in tissue homeostasis. The original klotho hypomorphic
      (klotho (hm) ) mouse, produced on a mixed C57BL/6 and C3H background, is short
      lived and exhibits extensive aging-like deterioration of several body systems.
      Differently, klotho (hm) mice on a pure C57BL/6 background do not appear sickly
      nor die young, which has permitted us to gain insight into the effect of klotho
      deficiency in adult life. First, analyzing klotho transcript levels in the
      kidney, the main site of klotho production, we demonstrated a 71-fold decline in
      klotho (hm) females compared to wildtype females versus only a 4-fold decline in
      mutant males. We then examined the effect of klotho deficiency on muscle-related
      attributes in adult mice, focusing on 7-11 month old females. Body weight and
      forelimb grip strength were significantly reduced in klotho (hm) mice compared to
      wildtype and klotho overexpressing mice. The female mice were also subjected to
      voluntary wheel running for a period of 6 days. Running endurance was markedly
      reduced in klotho (hm) mice, which exhibited a sporadic running pattern that may
      be characteristic of repeated bouts of exhaustions. When actually running, klotho
      (hm) females ran at the same speed as wildtype and klotho overexpressing mice,
      but spent about 65 % less time running compared to the other two groups. Our
      novel results suggest an important link between klotho deficiency and muscle
      performance. This study provides a foundation for further research on klotho
      involvement as a potential inhibitor of age-associated muscle deterioration. 

PMID- 24030244
TI  - Post-polypectomy colonoscopy surveillance: European Society of Gastrointestinal
      Endoscopy (ESGE) Guideline.
AB  - MAIN RECOMMENDATIONS: The following recommendations for post-polypectomy
      endoscopic surveillance should be applied only after a high quality baseline
      colonoscopy with complete removal of all detected neoplastic lesions.1 In the low
      risk group (patients with 1 - 2 tubular adenomas < 10 mm with low grade
      dysplasia), the ESGE recommends participation in existing national screening
      programmes 10 years after the index colonoscopy. If no screening programme is
      available, repetition of colonoscopy 10 years after the index colonoscopy is
      recommended (strong recommendation, moderate quality evidence). 2 In the high
      risk group (patients with adenomas with villous histology or high grade dysplasia
      or >=10 mm in size, or >= 3 adenomas), the ESGE recommends surveillance
      colonoscopy 3 years after the index colonoscopy (strong recommendation, moderate
      quality evidence). Patients with 10 or more adenomas should be referred for
      genetic counselling (strong recommendation, moderate quality evidence). 3 In the
      high risk group, if no high risk adenomas are detected at the first surveillance
      examination, the ESGE suggests a 5-year interval before a second surveillance
      colonoscopy (weak recommendation, low quality evidence). If high risk adenomas
      are detected at first or subsequent surveillance examinations, a 3-year
      repetition of surveillance colonoscopy is recommended (strong recommendation, low
      quality evidence).4 The ESGE recommends that patients with serrated polyps < 10
      mm in size with no dysplasia should be classified as low risk (weak
      recommendation, low quality evidence). The ESGE suggests that patients with large
      serrated polyps (>= 10 mm) or those with dysplasia should be classified as high
      risk (weak recommendation, low quality evidence).5 The ESGE recommends that the
      endoscopist is responsible for providing a written recommendation for the post
      polypectomy surveillance schedule (strong recommendation, low quality evidence).

PMID- 24030245
TI  - Correlation between peak intraocular pressure of the water drinking test and peak
      intraocular pressure induced by intravenous methylprednisolone pulse therapy.
AB  - PURPOSE: It was the aim of this study to determine any possible correlation
      between the peaks and changes in intraocular pressure (IOP) of a water drinking
      test and intravenous methylprednisolone pulse therapy (IVMPT) IOP response.
      METHODS: Patients with rheumatic disorders scheduled for IVMPT with normal ocular
      examination received a WDT before and after 3 days of IVMPT. The maximum value of
      IOPs detected during the WDT or IVMPT was regarded as peak IOP, and IOP change
      was defined as the difference between peak IOP and baseline IOP. RESULTS: The
      mean +/- standard deviation (SD) IOPs on the first (21.9 +/- 4.6 mm Hg; p =
      0.04), second (21.9 +/- 4.1 mm Hg; p = 0.03) and third (21.3 +/- 4.2 mm Hg; p =
      0.01) days of 20 enrolled patients were greater than that at baseline (19.3 +/-
      2.8 mm Hg). The mean +/- SD of peak IVMPT IOP response was 23.9 +/- 3.7 mm Hg,
      and IVMPT IOP change was 4.6 +/- 3.7 mm Hg. These values for the first and second
      WDTs were 22.9 +/- 4.9 and 3.9 +/- 4.07 as well as 24.1 +/- 4.6 and 3.00 +/- 2.9
      mm Hg, respectively. A significant correlation was observed between the first WDT
      and IVMPT IOP changes (r = 0.5, p = 0.007) and peak IOPs (r = 0.6, p = 0.001).
      CONCLUSION: WDT, a low-cost and feasible test in clinical practice, may be a
      useful tool in determining the IOP peak and change following IVMPT.

PMID- 24030247
TI  - Experimental realization of a delayed-choice quantum walk.
AB  - Many paradoxes of quantum mechanics come from the fact that quantum systems can
      possess different features simultaneously, such as in wave-particle duality or
      quantum superposition. In recent delayed-choice experiments, a quantum system can
      be observed to manifest one feature such as the wave or particle nature,
      depending on the measurement setup, which is chosen after the system itself has
      already entered the measuring device; hence its behaviour is not predetermined.
      Here we adapt this paradigmatic scheme to multi-dimensional quantum walks. In our
      experiment, the way in which a photon interferes with itself in a strongly non
      trivial pattern depends on its polarization, which is determined after the photon
      has already been detected. This is the first experiment realizing a multi
      dimensional quantum walk with a single photon source and we present also the
      first experimental simulation of the Grover walk, a model that can be used to
      implement the Grover quantum search algorithm. 

PMID- 24030248
TI  - Poison ivy dermatitis.

PMID- 24030246
TI  - Neuropsychological decline in schizophrenia from the premorbid to the postonset
      period: evidence from a population-representative longitudinal study.
AB  - OBJECTIVE: Despite the widespread belief that neuropsychological decline is a
      cardinal feature of the progression from the premorbid stage to the chronic form
      of schizophrenia, few longitudinal studies have examined change in
      neuropsychological functioning from before to after illness onset. The authors
      examined whether neuropsychological decline is unique to schizophrenia, whether
      it is generalized or confined to particular mental functions, and whether
      individuals with schizophrenia also have cognitive problems in everyday life.
      METHOD: Participants were members of a representative cohort of 1,037 individuals
      born in Dunedin, New Zealand, in 1972 and 1973 and followed prospectively to age
      38, with 95% retention. Assessment of IQ and specific neuropsychological
      functions was conducted at ages 7, 9, 11, and 13, and again at age 38. Informants
      also reported on any cognitive problems at age 38. RESULTS: Individuals with
      schizophrenia exhibited declines in IQ and in a range of mental functions,
      particularly those tapping processing speed, learning, executive function, and
      motor function. There was little evidence of decline in verbal abilities or
      delayed memory, however, and the developmental progression of deficits in
      schizophrenia differed across mental functions. Processing speed deficits
      increased gradually from childhood to beyond the early teen years, whereas verbal
      deficits emerged early but remained static thereafter. Neuropsychological decline
      was specific to schizophrenia, as no evidence of decline was apparent among
      individuals with persistent depression, children with mild cognitive impairment,
      individuals matched on childhood risk factors for schizophrenia, and
      psychiatrically healthy individuals. Informants also noticed more cognitive
      problems in individuals with schizophrenia. CONCLUSIONS: There is substantial
      neuropsychological decline in schizophrenia from the premorbid to the postonset
      period, but the extent and developmental progression of decline varies across
      mental functions. Findings suggest that different pathophysiological mechanisms
      may underlie deficits in different mental functions.

PMID- 24030249
TI  - Performance of the Parent Report of Children's Abilities-Revised (PARCA-R) versus
      the Bayley Scales of Infant Development III.
AB  - BACKGROUND: The Parent Report of Children's Abilities-Revised (PARCA-R) assesses
      cognitive and language development at 24 months. It was validated against the
      Mental Development Index of the Bayley Scales of Infant Development II (BSID II),
      but this has now been superseded by BSID III. OBJECTIVE: To compare the PARCA-R
      against the BSID III. METHODS: PARCA-R and BSID III assessments scheduled at 24
      months of age (corrected for prematurity) were completed in 204 infants with
      suspected or proven neonatal sepsis in the International Neonatal Immunotherapy
      Study. Associations between the scales were measured and the predictive accuracy
      of the PARCA-R for moderate cognitive delay and moderate language delay was
      assessed using Receiver Operating Characteristic (ROC) analysis. RESULTS: Median
      birthweight was 911 g, median gestational age at birth was 27 weeks and 100
      (49.0%) were girls. 4.4% and 8.4% met standard BSID III criteria for cognitive
      delay and language delay, respectively. These rates increased to 19.6% and 12.6%
      when an independent sample of normal term infants were used as the reference
      group suggesting standard BSID III reference norms may tend to underestimate
      delay. The Spearman correlation between PARCA-R and BSID scales were 0.43 for
      cognition and 0.71 for language. The PARCA-R successfully predicted cases of
      cognitive delay and language delay with the area under the ROC curves ranging
      from 0.83 to 0.97 depending on reference norms used. CONCLUSIONS: The results
      support the PARCA-R as a practical tool for the identification of appreciable
      cognitive and language delay at 24 months among critically ill premature and
      extremely low birthweight neonates.

PMID- 24030250
TI  - Glucose transporter-8 (GLUT8) mediates glucose intolerance and dyslipidemia in
      high-fructose diet-fed male mice.
AB  - Members of the glucose transporter (GLUT) family of membrane-spanning hexose
      transporters are subjects of intensive investigation for their potential as
      modifiable targets to treat or prevent obesity, metabolic syndrome, and type 2
      diabetes mellitus. Mounting evidence suggests that the ubiquitously expressed
      class III dual-specificity glucose and fructose transporter, GLUT8, has important
      metabolic homeostatic functions. We therefore tested the hypothesis that GLUT8
      mediates the deleterious metabolic effects of chronic high-fructose diet
      exposure. Here we demonstrate resistance to high-fructose diet-induced glucose
      intolerance and dyslipidemia concomitant with enhanced oxygen consumption and
      thermogenesis in GLUT8-deficient male mice. Independent of diet, significantly
      lower systolic blood pressure both at baseline and after high-fructose diet
      feeding was also observed by tail-cuff plethysmography in GLUT8-deficient mice vs
      wild-type controls. Resistance to fructose-induced metabolic dysregulation
      occurred in the context of enhanced hepatic peroxisome proliferator antigen
      receptor-gamma (PPARgamma) protein abundance, whereas in vivo hepatic adenoviral
      GLUT8 overexpression suppressed hepatic PPARgamma expression. Taken together,
      these findings suggest that GLUT8 blockade prevents fructose-induced metabolic
      dysregulation, potentially by enhancing hepatic fatty acid metabolism through
      PPARgamma and its downstream targets. We thus establish GLUT8 as a promising
      target in the prevention of diet-induced obesity, metabolic syndrome, and type 2
      diabetes mellitus in males. 

PMID- 24030251
TI  - Advanced glycated end-products affect HIF-transcriptional activity in renal
      cells.
AB  - Advanced glycated end-products (AGEs) are ligands of the receptor for AGEs and
      increase in diabetic disease. MAPK organizer 1 (Morg1) via its binding partner
      prolyl-hydroxylase domain (PHD)-3 presumably plays a role in the regulation of
      hypoxia-inducible factor (HIF)-1alpha and HIF-2alpha transcriptional activation.
      The purpose of this study was to analyze the influence of AGEs on Morg1
      expression and its correlation to PHD3 activity and HIF-transcriptional activity
      in various renal cell types. The addition of glycated BSA (AGE-BSA) significantly
      up-regulated Morg1 mRNA levels in murine mesangial cells and down-regulated it in
      murine proximal tubular cells and differentiated podocytes. These effects were
      reversible when the cells were preincubated with a receptor for alpha-AGE
      antibody. AGE-BSA treatment induced a relocalization of the Morg1 cellular
      distribution compared with nonglycated control-BSA. Analysis of PHD3 activity
      demonstrated an elevated PHD3 enzymatic activity in murine mesangial cells but an
      inhibition in murine proximal tubular cells and podocytes after the addition of
      AGE-BSA. HIF-transcriptional activity was also affected by AGE-BSA treatment.
      Reporter gene assays and EMSAs showed that AGEs regulate HIF- transcriptional
      activity under nonhypoxic conditions in a cell type-specific manner. In proximal
      tubular cells, AGE-BSA stimulation elevated mainly HIF-1alpha transcriptional
      activity and to a lesser extent HIF-2alpha. We also detected an increased
      expression of the HIF-1alpha and the HIF-2alpha proteins in kidneys from Morg1
      heterozygous (HZ) placebo mice compared with the Morg1 wild-type (WT) placebo
      treated mice, and the HIF-1alpha protein expression in the Morg1 HZ
      streptozotocin-treated mice was significantly higher than the WT streptozotocin
      treated mice. Analysis of isolated mesangial cells from Morg1 HZ (+/-) and WT
      mice showed an inhibited PHD3 activity and an increased HIF-transcriptional
      activity in cells with only one Morg1 allele. These findings are important for a
      better understanding of the molecular mechanisms of diabetic nephropathy. 

PMID- 24030253
TI  - Microbiomarkers with big impact in CLL.

PMID- 24030254
TI  - Better late than never?

PMID- 24030252
TI  - IGF-1R modulation of acute GH-induced STAT5 signaling: role of protein tyrosine
      phosphatase activity.
AB  - GH is a potent anabolic and metabolic factor that binds its cell surface receptor
      (GHR), activating the GHR-associated tyrosine kinase, Janus kinase 2, which
      phosphorylates and activates the latent transcription factor, signal transducer
      and activator of transcription 5 (STAT5). Some GH actions are mediated by the
      elaboration of IGF-1, which exerts effects by binding and activating the
      heterotetrameric tyrosine kinase growth factor receptor, IGF-1R. In addition to
      this GH-GHR-IGF-1-IGF-1R scheme, we have demonstrated in primary osteoblasts and
      in islet beta-cells that then deletion or silencing of IGF-1R results in
      diminished GH-induced STAT5 phosphorylation, suggesting that the presence of IGF
      1R may facilitate GH signaling. In this study, we explore potential roles for
      protein tyrosine phosphatase activity in modulating GH-induced signaling,
      comparing conditions in which IGF-1R is present or diminished. We confirm that in
      mouse primary osteoblasts harboring loxP sites flanking the IGF-1R gene,
      infection with an adenovirus that expresses the Cre recombinase results in IGF-1R
      deletion and diminished acute GH-induced STAT5 phosphorylation. Furthermore, we
      present a new model of IGF-1R silencing, in which expression of short hairpin RNA
      directed at IGF-1R greatly reduces IGF-1R abundance in LNCaP human prostate
      cancer cells. In both models, treatment with a chemical inhibitor of protein
      tyrosine phosphatase-1B (PTP-1B), but not one of src homology region 2 domain
      containing phosphotase-1 (SHP-1) and SHP-2, reverses the loss of GH-induced STAT5
      phosphorylation in cells lacking IGF-1R but has no effect in cells with intact
      IGF-1R. Furthermore, expression of either a dominant-negative PTP-1B or the PTP
      1B-interacting inhibitory protein, constitutive photomorphogenesis 1, also
      rescues acute GH-induced STAT5 signaling in IGF-1R-deficient cells but has no
      effect in IGF-1R replete cells. By expressing a substrate-trapping mutant PTP-1B,
      we demonstrate that tyrosine phosphorylated Janus kinase-2 is a PTP-1B substrate
      only in cells lacking IGF-1R. Collectively, our data suggest that IGF-1R
      positively regulates acute GH signaling by preventing access of PTP-1B activity
      to Janus kinase 2 and thereby preventing PTP-1B-mediated suppression of GH
      induced STAT5 activation. 

PMID- 24030255
TI  - GLEE-ful for sickle cell pain?

PMID- 24030256
TI  - Attack of the T-cell clones.

PMID- 24030257
TI  - From nuclear to a global family: more donors for MDS.

PMID- 24030258
TI  - In vivo evidence insufficient to conclude that "KIR/HLA incompatibility between
      sexual partners confers protection against HIV-1 transmission".

PMID- 24030259
TI  - Response: KIR/HLA incompatibility in HIV-1 transmission and importance of the
      'missing self' model.

PMID- 24030260
TI  - Molecular classification of mature aggressive B-cell lymphoma using digital
      multiplexed gene expression on formalin-fixed paraffin-embedded biopsy specimens.

PMID- 24030261
TI  - ANKRD26-related thrombocytopenia and myeloid malignancies.

PMID- 24030262
TI  - Plasma hepcidin of Ethiopian highlanders with steady-state hypoxia.

PMID- 24030263
TI  - Fcgamma receptor IIB gene polymorphism in adult Japanese patients with primary
      immune thrombocytopenia.

PMID- 24030264
TI  - Genome-wide DNA methylation assay reveals novel candidate biomarker genes in
      cervical cancer.
AB  - The oncogenic human papilloma viruses (HPVs) are associated with precancerous
      cervical lesions and development of cervical cancer. The DNA methylation
      signatures of the host genome in normal, precancerous and cervical cancer tissue
      may indicate tissue-specific perturbation in carcinogenesis. The aim of this
      study was to identify new candidate genes that are differentially methylated in
      squamous cell carcinoma compared with DNA samples from cervical intraepithelial
      neoplasia grade 3 (CIN3) and normal cervical scrapes. The Illumina Infinium
      HumanMethylation450 BeadChip method identifies genome-wide DNA methylation
      changes in CpG islands, CpG shores and shelves. Our findings showed an extensive
      differential methylation signature in cervical cancer compared with the CIN3 or
      normal cervical tissues. The identified candidate biomarker genes for cervical
      cancer represent several types of mechanisms in the cellular machinery that are
      epigenetically deregulated by hypermethylation, such as membrane receptors,
      intracellular signaling and gene transcription. The results also confirm
      extensive hypomethylation of genes in the immune system in cancer tissues. These
      insights into the functional role of DNA methylome alterations in cervical cancer
      could be clinically applicable in diagnostics and prognostics, and may guide the
      development of new epigenetic therapies. 

PMID- 24030265
TI  - Investing in malaria research in challenging financial times.

PMID- 24030266
TI  - Appointment systems are essential for improving chronic disease care in resource
      poor settings: learning from experiences with HIV patients in Africa.
AB  - Lessons learned from treating patients with HIV infection can inform care systems
      for other chronic conditions. For antiretroviral treatment, attending
      appointments on time correlates with medication adherence; however, HIV clinics
      in East Africa, where attendance rates vary widely, rarely include systems to
      schedule appointments or to track missed appointments or patient follow-up. An
      introduction of low-cost, paper-based patient appointment and tracking systems
      led to an improvement in timely clinic attendance rates and tracking missing
      patients. An effective appointment system is critical to managing patients with
      chronic conditions and can be introduced in resource-limited settings, possibly
      without having to add staff. 

PMID- 24030267
TI  - Japanese encephalitis in India: risk of an epidemic in the National Capital
      Region.
AB  - Japanese encephalitis (JE) is a mosquitoborne viral disease that is the primary
      cause of acute encephalitis syndrome in India. This virus mainly infects the
      central nervous system and causes massive inflammation which, if left unchecked,
      may prove fatal. Survivors often suffer from mild to severe neuropsychiatric
      sequelae. JE is a major cause of death in many parts of India and there is a
      possibility of it spreading into the National Capital Region from highly endemic
      neighbouring states. Fourteen cases of JE were reported in Delhi in 2011 compared
      with none in the previous 4 years from 2007 to 2010. Unless immediate preventive
      measures are taken this trend could continue and the disease could spread with
      increasing prevalence. 

PMID- 24030268
TI  - Community-based antiretroviral therapy programs can overcome barriers to
      retention of patients and decongest health services in sub-Saharan Africa: a
      systematic review.
AB  - In sub-Saharan Africa models of care need to adapt to support continued scale up
      of antiretroviral therapy (ART) and retain millions in care. Task shifting,
      coupled with community participation has the potential to address the workforce
      gap, decongest health services, improve ART coverage, and to sustain retention of
      patients on ART over the long-term. The evidence supporting different models of
      community participation for ART care, or community-based ART, in sub-Saharan
      Africa, was reviewed. In Uganda and Kenya community health workers or volunteers
      delivered ART at home. In Mozambique people living with HIV/AIDS (PLWHA) self
      formed community-based ART groups to deliver ART in the community. These examples
      of community ART programs made treatment more accessible and affordable. However,
      to achieve success some major challenges need to be overcome: first, community
      programs need to be driven, owned by and embedded in the communities. Second, an
      enabling and supportive environment is needed to ensure that task shifting to lay
      staff and PLWHA is effective and quality services are provided. Finally, a long
      term vision and commitment from national governments and international donors is
      required. Exploration of the cost, effectiveness, and sustainability of the
      different community-based ART models in different contexts will be needed. 

PMID- 24030270
TI  - Community case management of malaria: a pro-poor intervention in rural Kenya.
AB  - BACKGROUND: Access to prompt and effective treatment of malaria is a fundamental
      right of all populations at risk; many countries have not met the target of 60%
      of children treated with effective antimalarial drugs within 24 h of fever onset.
      While community case management of malaria is effective for increasing coverage,
      evidence is mixed on whether it improves equity. The objective of this study was
      to assess whether a community case management of a malaria programme delivered by
      community health workers (CHW) in two districts of Kenya improved access and
      equity. METHODS: Data on child fever treatment practices, malaria prevention and
      CHW visits was collected through cross-sectional household surveys in project
      communities before (December 2008) and after 1 year of intervention (December
      2009). Indicators were analysed by household wealth rank (grouped into poorest
      [bottom 20%], poor [middle 60%] and least poor [top 20%]) and survey. RESULTS:
      Data were available from 763 households at baseline and 856 households at
      endline. At endline, access to prompt and effective malaria treatment was higher
      compared with baseline for all groups, with the highest proportions among the
      poorest (67.6%) and the poor (63.2%), and the lowest proportion among the least
      poor (43.4%). Corresponding data suggest this was linked to the household's
      interaction with a CHW as the source of advice/treatment for child fever.
      CONCLUSION: These findings provide evidence that in a resource-poor setting, CHWs
      can provide lifesaving interventions to the poorest.

PMID- 24030269
TI  - Effects of quality improvement in health facilities and community mobilization
      through women's groups on maternal, neonatal and perinatal mortality in three
      districts of Malawi: MaiKhanda, a cluster randomized controlled effectiveness
      trial.
AB  - BACKGROUND: Maternal, perinatal and neonatal mortality remains high in low-income
      countries. We evaluated community and facility-based interventions to reduce
      deaths in three districts of Malawi. METHODS: We evaluated a rural participatory
      women's group community intervention (CI) and a quality improvement intervention
      at health centres (FI) via a two-by-two factorial cluster randomized controlled
      trial. Consenting pregnant women were followed-up to 2 months after birth using
      key informants. Primary outcomes were maternal, perinatal and neonatal mortality.
      Clusters were health centre catchment areas assigned using stratified computer
      generated randomization. Following exclusions, including non-birthing facilities,
      61 clusters were analysed: control (17 clusters, 4912 births), FI (15, 5335), CI
      (15, 5080) and FI + CI (14, 5249). This trial was registered as International
      Standard Randomised Controlled Trial [ISRCTN18073903]. Outcomes for 14,576 and
      20,576 births were recorded during baseline (June 2007-September 2008) and
      intervention (October 2008-December 2010) periods. RESULTS: For control, FI, CI
      and FI + CI clusters neonatal mortality rates were 34.0, 28.3, 29.9 and 27.0
      neonatal deaths per 1000 live births and perinatal mortality rates were 56.2,
      55.1, 48.0 and 48.4 per 1000 births, during the intervention period. Adjusting
      for clustering and stratification, the neonatal mortality rate was 22% lower in
      FI + CI than control clusters (OR = 0.78, 95% CI 0.60-1.01), and the perinatal
      mortality rate was 16% lower in CI clusters (OR = 0.84, 95% CI 0.72-0.97). We did
      not observe any intervention effects on maternal mortality. CONCLUSIONS: Despite
      implementation problems, a combined community and facility approach using
      participatory women's groups and quality improvement at health centres reduced
      newborn mortality in rural Malawi.

PMID- 24030271
TI  - Pediatricians' perceptions of vaccine effectiveness and safety are significant
      predictors of vaccine administration in India.
AB  - BACKGROUND: New vaccine introduction is important to decrease morbidity and
      mortality in India. The goal of this study was to identify perceptions that are
      associated with administration of four selected vaccines for prevention of
      Japanese encephalitis (JE), typhoid fever, influenza and human papillomavirus
      (HPV) infection. METHODS: A random sample of 785 pediatricians from a national
      list of Indian Academy of Pediatrics members was selected for a survey to assess
      perceptions of vaccine effectiveness and safety, and vaccine administration
      practices. Logistic regression was used to assess factors associated with
      selective or routine use. RESULTS: Pediatricians reported administering typhoid
      (91.6%), influenza (60.1%), HPV (46.0%) and JE (41.9%) vaccines selectively or
      routinely. Pediatricians who perceived the vaccine to be safe were significantly
      more likely to report administration of JE (OR 2.6, 95% CI 1.3 to 5.3), influenza
      (OR 4.3, 95% CI 2.0 to 9.6) and HPV vaccine (OR 6.2, 95% CI 3.1 to 12.7).
      Pediatricians who perceived the vaccine to be effective were significantly more
      likely to report administration of JE (OR 3.3, 95% CI 1.6 to 6.5), influenza (OR
      7.7, 95% CI 2.5 to 23.1) and HPV vaccine (OR 3.2, 95% CI 1.6 to 6.4) CONCLUSION:
      Understanding the role perceptions play provides an opportunity to design
      strategies to build support for vaccine use.

PMID- 24030272
TI  - Prevalence of malaria and use of malaria risk reduction measures among resettled
      pregnant women in South Sudan.
AB  - BACKGROUND: The study assessed aspects of malaria infection, prevention and
      treatment in a population of resettled pregnant women in South Sudan. METHODS:
      During April and May 2008, a cross-sectional study was carried out to estimate
      malaria prevalence and to assess the use of malaria risk reduction measures and
      their associations with selected background characteristics. Two hundred and
      twenty women were tested for malaria parasitaemia and questioned about their
      malaria prevention and treatment practices. RESULTS: The results showed a
      prevalence of Plasmodium falciparum parasitaemia of 9.1%. No statistically
      significant associations were observed between selected background
      characteristics and malaria infection status. However, school attendance was
      significantly associated with insecticide-treated net ownership (OR = 6.52, 95%
      CI 2.37-17.94; p = 0.001) and access to malaria diagnosis and treatment (OR =
      3.20, 95% CI 1.26-8.16; p = 0.015). CONCLUSIONS: The results suggest that
      educational attainment need not be very advanced to affect practices of malaria
      prevention and treatment. Primary school attendance was a stronger predictor for
      use of malaria risk reduction measures than any of the other selected background
      characteristics. Educational attainment, information and communication about
      malaria prevention and control play a pivotal role in increasing and improving
      use of malaria risk reduction measures.

PMID- 24030273
TI  - Training of community healthcare providers and TB case detection in Bangladesh.
AB  - BACKGROUND: For several years, BRAC (previously known as the Bangladesh Rural
      Advancement Committee) has been assisting with national TB control efforts in
      Bangladesh and has especially focused on training of community healthcare
      personnel. This study attempts to determine whether there is any association
      between a community-based TB training programme in peri-urban Dhaka and TB case
      finding within the same catchment area. METHODS: This was a cross-sectional
      retrospective study using laboratory sputum registers and annual BRAC training
      reports. RESULTS: Between 2005 and 2010, there were 536 training activities for
      community healthcare providers with 9037 people trained. Numbers of patients
      attending laboratories with suspected TB increased from 8211 in 2004 (before
      training) to 10 961 in 2005 (start of training) with the proportion diagnosed
      with smear-positive TB increasing from 7.1% to 11.2%. Thereafter, the numbers
      with suspected and diagnosed TB remained similar up to 2010. The most important
      sources of referral of patients for investigation were community health
      volunteers and self-referring patients accounting for 58% of all patients.
      CONCLUSION: In this operational research study in peri-urban Dhaka, there was an
      initial increase in TB case finding with numbers then reaching a plateau despite
      continued training activities. Further prospective evaluation is required to
      understand these phenomena.

PMID- 24030276
TI  - White-light emitting boronate microparticles for potential use as reusable bright
      chemosensors in water.
AB  - The facile surface functionalization of surfactant-free organic microparticles
      composed of polymeric 2,4,8,10-tetraoxa-3,9-diboraspiro[5.5]undecane allowed us
      to develop white-light emissive chemosensors for the real-time visual detection
      of Cu(2+) in HEPES buffer (pH 7.0) due to a synergistic response of fluorophores
      grafted onto the particles. A detection limit of 15.4 ppb for Cu(2+) in aqueous
      media and excellent recyclability were also observed. 

PMID- 24030274
TI  - Impact of treating young children with antimalarials with or without antibiotics
      on morbidity: a cluster-randomized controlled trial in Ghana.
AB  - BACKGROUND: Community health workers in Dangme-West district, Ghana, treated
      children aged 2-59 months with fever with either artesunate-amodiaquine (AAQ) or
      AAQ plus amoxicillin (AAQ + AMX) within a cluster-randomized controlled trial
      (registration no. TDR/UNDP Trial registration A: 20189). The intervention was
      introduced in a stepped-wedge manner. The aim of the study was reduction of
      mortality. This paper reports on the reduction of morbidity, notably anaemia,
      severe anaemia and severe illness. Clusters of 100 children were randomized in to
      AAQ, AAQ + AMX and pre-intervention arms. Six months later the pre-intervention
      clusters were randomized in to the AAQ and AAQ + AMX arms. METHODS: Data were
      collected in eight cross-sectional surveys. Using stratified sampling, 10
      clusters were randomly selected per survey. Blood samples were taken to assess
      haemoglobin. Caregivers were interviewed about diseases (signs and symptoms)
      among their children in the preceding 14 days. Multivariate logistic regression
      analysis was used to determine the impact on anaemia, severe anaemia and severe
      illness. RESULTS: Compared with the pre-intervention clusters, anaemia was
      reduced in the AAQ (OR = 0.20, 95% CI 0.12-0.33) and AAQ + AMX (OR = 0.23, 95% CI
      0.15-0.36) clusters, severe anaemia was reduced in the AAQ (OR = 0.20, 95% CI
      0.09-0.45) and AAQ + AMX (OR = 0.12, 95% CI 0.04-0.31) clusters and severe
      illness was reduced in the AAQ (OR = 0.46, 95% CI 0.26-0.80) and AAQ + AMX (OR =
      0.38, 95% CI 0.22-0.63) clusters. No significant differences were found in
      outcome variables between the AAQ and AAQ + AMX clusters. CONCLUSIONS: Treating
      fever with antimalarials significantly reduced the prevalence of anaemia, severe
      anaemia and severe illness. We found no significant reduction in outcomes when
      the AAQ and AAQ+AMX clusters were compared.

PMID- 24030275
TI  - Efficient new constructs against triple negative breast cancer cells: synthesis
      and preliminary biological study of ferrocifen-SAHA hybrids and related species.
AB  - Chemotherapeutic agents combining several active groups within a single molecule
      can modulate multiple cellular pathways and, thus, exhibit higher efficacy than
      single-target drugs. In this study, six new hybrid compounds combining tamoxifen
      (TAM) or ferrocifen (FcTAM) structural motifs with suberoylanilide hydroxamic
      acid (SAHA) were synthesised and evaluated. Antiproliferative activity was first
      explored in cancer cell lines. Combining FcTAM and SAHA structural motifs to form
      the unprecedented FcTAM-SAHA hybrid molecule led to an increased cytotoxicity
      (IC50 = 0.7 MUM) in triple-negative MDA-MB-231 breast cancer cells when compared
      to FcTAM or SAHA alone (IC50 = 2.6 MUM and 3.6 MUM, respectively), while the
      organic hybrid analogue TAM-SAHA was far less cytotoxic (IC50 = 8.6 MUM). In
      hormone-dependent MCF-7 breast cancer cells, FcTAM-SAHA was more active (IC50 =
      2.0 MUM) than FcTAM (IC50 = 4.4 MUM) and TAM-SAHA (IC50 > 10 MUM), but less toxic
      than SAHA (IC50 = 1.0 MUM). Surprisingly, FcTAM-PSA, an N1-phenylsuberamide
      derivative, also possessed strong antiproliferative activity (IC50 = 0.5 MUM and
      1.8 MUM in MDA-MB-231 and MCF-7 cells, respectively). Subsequent biochemical
      studies indicate that estrogen receptor alpha (ERalpha) and histone deacetylases
      (HDAC) are not the main targets of the hybrid compounds for their
      antiproliferative effect. Interestingly, both organometallic compounds were able
      to induce p21waf1/cip1 gene expression in MCF-7 breast cancer cells in accordance
      with their antiproliferative activity.

PMID- 24030277
TI  - The A to T of historical evidence. Historians, archaeologists and geneticists are
      teaming up to answer historical questions.

PMID- 24030278
TI  - Nucleosome dynamics regulate Neurospora circadian clock.

PMID- 24030279
TI  - Gene patents and capital investment. The consequences of the revocation of
      Myriad's patents on the BRCA genes on venture capital investment in the life
      sciences.

PMID- 24030280
TI  - The Henrietta Lacks legacy grows.

PMID- 24030281
TI  - Brothers in arms. Military funding for basic and applied biomedical science is
      thriving, with civilian applications delivered along the way.

PMID- 24030283
TI  - A transient reversal of miRNA-mediated repression controls macrophage activation.
AB  - In mammalian macrophages, the expression of a number of cytokines is regulated by
      miRNAs. Upon macrophage activation, proinflammatory cytokine mRNAs are
      translated, although the expression of miRNAs targeting these mRNAs remains
      largely unaltered. We show that there is a transient reversal of miRNA-mediated
      repression during the early phase of the inflammatory response in macrophages,
      which leads to the protection of cytokine mRNAs from miRNA-mediated repression.
      This derepression occurs through Ago2 phosphorylation, which results in its
      impaired binding to miRNAs and to the corresponding target mRNAs. Macrophages
      expressing a mutant, non-phosphorylatable AGO2--which remains bound to miRNAs
      during macrophage activation--have a weakened inflammatory response and fail to
      prevent parasite invasion. These findings highlight the relevance of the
      transient relief of miRNA repression for macrophage function.

PMID- 24030282
TI  - The joy of sex pheromones.
AB  - Sex pheromones provide an important means of communication to unite individuals
      for successful reproduction. Although sex pheromones are highly diverse across
      animals, these signals fulfil common fundamental roles in enabling identification
      of a mating partner of the opposite sex, the appropriate species and of optimal
      fecundity. In this review, we synthesize both classic and recent investigations
      on sex pheromones in a range of species, spanning nematode worms, insects and
      mammals. These studies reveal comparable strategies in how these chemical signals
      are produced, detected and processed in the brain to regulate sexual behaviours.
      Elucidation of sex pheromone communication mechanisms both defines outstanding
      models to understand the molecular and neuronal basis of chemosensory behaviours,
      and reveals how similar evolutionary selection pressures yield convergent
      solutions in distinct animal nervous systems.

PMID- 24030284
TI  - Role of long non-coding RNAs in normal and malignant hematopoiesis.
AB  - Long non-coding RNAs (lncRNAs) are defined as a class of nonprotein-coding
      transcripts greater than 200 nucleotides in length, which have diverse functions
      in development and diseases including hematopoiesis. Recent advances have
      revealed that lncRNAs regulate hematopoietic development at almost every stage,
      including differentiation of the myelocyte, lymphocyte, and erythrocyte. Abnormal
      regulation of the lncRNAs may block aspects of blood development, which can lead
      to different types of hematopoietic disorders. These findings highlight the role
      of lncRNAs as potential therapeutic tools in malignant hematopoiesis. In this
      review, we summarize recent progress in the study of functional lncRNAs
      associated with blood development, as well as dysregulated lncRNAs involved in
      diverse blood diseases by interacting with crucial susceptibility genes in
      different pathways. In addition, we discuss genome-wide studies on lncRNAs, which
      are helpful for genome screening and in-depth functional study of lncRNAs
      associated with blood development and disease. 

PMID- 24030285
TI  - Increased active PTH(1-84) fraction as a predictor of poor mortality in male
      hemodialysis patients.
AB  - We reported previously that serum parathyroid hormone [PTH(1-84)]/intact
      PTH[PTH(1-84) + PTH(7-84)] ratio provides the better marker for parathyroid
      function and bone turnover state than serum PTH level itself. The present study
      demonstrated that higher PTH(1-84)/intact PTH ratio, but not serum PTH(1-84) and
      intact PTH, predicted higher all-cause mortality in 177 male hemodialysis
      patients. INTRODUCTION: We reported that PTH(1-84)/intact PTH ratio provides a
      clinically relevant marker for parathyroid function and the resultant bone
      turnover state. The purpose of our study was to investigate the association of
      PTH(1-84)/intact PTH ratio with all-cause mortality (ACM) in male hemodialysis
      patients. METHODS: The study was performed for 70 months. Serum PTH in 177 male
      hemodialysis patients was measured with PTH(1-84)-specific whole PTH assay and
      intact PTH assay which cross-reacts with N-truncated PTH including PTH(7-84).
      RESULTS: The patients (n = 177) were divided into higher and lower halves based
      on serum levels of PTH(1-84)/intact PTH ratio (cutoff value, 0.484), intact PTH
      (143.8 pg/mL), and PTH(1-84) (64.1 pg/mL). In Kaplan-Meier analysis, the higher
      group in whole PTH/intact PTH ratio had significantly higher ACM than the lower
      group (P = 0.020 by log-rank test), in contrast with the insignificant difference
      between the higher and lower groups in intact PTH and PTH(1-84). Multivariate Cox
      regression hazard analysis identified higher log [PTH(1-84)/intact PTH ratio],
      but not log intact PTH or log PTH(1-84) as a significant independent predictor
      [hazard ratio 14.428 (95% CI 2.486-83.728)] for ACM after adjustment for various
      factors including age, hemodialysis duration, presence/absence of diabetes
      mellitus, BMI, log C-reactive protein, serum albumin, calcium, and phosphate. The
      association existed between log [PTH(1-84)/intact PTH ratio] and ACM in those
      without vitamin D administration (n = 95). CONCLUSION: Higher PTH(1-84)/intact
      PTH ratio, which provides a relevant marker for parathyroid function, may be a
      significant predictor of ACM in male hemodialysis patients.

PMID- 24030286
TI  - A brilliant breakthrough in OI type V.
AB  - Interferon-induced transmembrane protein 5 or bone-restricted ifitm-like gene
      (Bril) was first identified as a bone gene in 2008, although no in vivo role was
      identified at that time. A role in human bone has now been demonstrated with a
      number of recent studies identifying a single point mutation in Bril as the
      causative mutation in osteogenesis imperfecta type V (OI type V). Such a
      discovery suggests a key role for Bril in skeletal regulation, and the completely
      novel nature of the gene raises the possibility of a new regulatory pathway in
      bone. Furthermore, the phenotype of OI type V has unique and quite divergent
      features compared with other forms of OI involving defects in collagen biology.
      Currently it appears that the underlying genetic defect in OI type V may be
      unrelated to collagen regulation, which also raises interesting questions about
      the classification of this form of OI. This review will discuss current knowledge
      of OI type V, the function of Bril, and the implications of this recent
      discovery. 

PMID- 24030287
TI  - Optimizing fracture prevention: the fracture liaison service, an observational
      study.
AB  - The response rate to the invitation to the fracture liaison service and reasons
      for non-response were evaluated in 2,207 fragility fracture patients. Fifty-one
      percent responded; non-responders were most often not interested (38 %) or were
      hip fracture patients. After 1 year of treatment, 88 % was still persistent and 2
      % had a new fracture. INTRODUCTION: To increase the percentage of elderly
      fracture patients undergoing a dual energy x-ray absorptiometry (DXA)
      measurement, and to investigate why some patients did not respond to invitation
      to our fracture liaison service (FLS). METHODS: In four Dutch hospitals, fracture
      patients >= 50 years were invited through a written or personal invitation at the
      surgical outpatient department, for a DXA measurement and visit to our FLS.
      Patients who did not respond were contacted by telephone. In patients diagnosed
      with osteoporosis, treatment was started. Patients were contacted every 3 months
      during 1 year to assess drug persistence and the occurrence of subsequent
      fractures. RESULTS: Of the 2,207 patients who were invited, 50.6 % responded.
      Most frequent reasons for not responding included: not interested (38 %), already
      screened/under treatment for osteoporosis (15.7 %), physically unable to attend
      the clinic (11.5 %), and death (5.2 %). Hip fracture patients responded less
      frequently (29 %) while patients with a wrist (60 %) or ankle fracture (65.2 %)
      were more likely to visit the clinic. In 337 responding patients, osteoporosis
      was diagnosed and treatment was initiated. After 12 months of follow-up, 88 % of
      the patients were still persistent with anti-osteoporosis therapy and only 2 %
      suffered a subsequent clinical fracture. CONCLUSION: In elderly fracture
      patients, the use of a FLS leads to an increased response rate, a high
      persistence to drug treatment, and a low rate of subsequent clinical fractures.
      Additional programs for hip fracture patients are required, as these patients
      have a low response rate.

PMID- 24030288
TI  - The functional muscle-bone unit in subjects of varying BMD.
AB  - SUMMARY: This study used the "functional muscle-bone unit" concept to investigate
      muscle-bone interaction of the lumbar spine in subjects of varying bone mineral
      density. It was found that unit bone mass corresponded to a relatively more
      muscle mass in subjects with reduced bone mineral density, indicating a
      relatively higher mechanical load from muscles exerted on trabecular bone.
      INTRODUCTION: Bone is an architecturally adaptive tissue which responds to
      mechanical loading. This study is proposed to use "functional muscle-bone unit"
      to reflect this muscle-bone interaction at spine in subjects with different bone
      mineral density. METHODS: The study was carried out in young normal subjects (21
      females; age, 29 +/- 3) and elderly subjects (155 females; age, 73 +/- 3.9) with
      varying bone mineral density. Cross-sectional area of paravertebral muscle groups
      was measured in MR images to indicate the muscle mass, while the bone mineral
      content by dual X-ray absorptiometry was used to represent the bone mass. The
      functional muscle-bone unit was calculated as the ratio between the bone mass to
      muscle mass. RESULTS: It showed that with aging, the muscle mass decreased with
      the bone mass losing. However, more pronounced reduction was found in bone mass
      than in muscle mass in the subjects with lower bone mineral density. CONCLUSIONS:
      Muscle-bone interaction was changed in elderly, especially in those with
      osteoporosis. Unit bone mass corresponded to a higher muscle mass in subjects
      with reduced bone mineral density than those normal subjects. This may be
      contributory to the occurrence of nontraumatic vertebral fractures in elderly
      subjects with reduced bone mineral density.

PMID- 24030289
TI  - Charge enhancement of single-stranded DNA in negative electrospray ionization
      using the supercharging reagent meta-nitrobenzyl alcohol.
AB  - Charge enhancement of single-stranded oligonucleotide ions in negative ESI mode
      is investigated. The employed reagent, meta-nitrobenzyl alcohol (m-NBA), was
      found to improve total signal intensity (Itot), increase the highest observed
      charge states (zhigh), and raise the average charge states (zavg) of all tested
      oligonucleotides analyzed in negative ESI. To quantify these increases, signal
      enhancement ratios (SER1%) and charge enhancement coefficients (CEC1%) were
      introduced. The SER1%, (defined as the quotient of total oligonucleotide ion
      abundances with 1% m-NBA divided by total oligonucleotide abundance without m
      NBA) was found to be greater than unity for every oligonucleotide tested. The
      CEC1% values (defined as the average charge state in the presence of 1% m-NBA
      minus the average charge state in the absence of m-NBA) were found to be
      uniformly positive. Upon close inspection, the degree of charge enhancement for
      longer oligonucleotides was found to be dependent upon thymine density (i.e., the
      number and the location of phospho-thymidine units). A correlation between the
      charge enhancement induced by the presence of m-NBA and the apparent gas-phase
      acidity (largely determined by the sequence of thymine units but also by the
      presence of protons on other nucleobases) of multiply deprotonated
      oligonucleotide species, was thus established. Ammonium cations appeared to be
      directly involved in the m-NBA supercharging mechanism, and their role seems to
      be consistent with previously postulated ESI mechanisms describing
      desorption/ionization of single-stranded DNA into the gas phase.

PMID- 24030291
TI  - In vitro permeability study of CNS-active diterpenes from Sideritis spp. using
      cellular models of blood-brain barrier.
AB  - The major diterpenes andalusol, conchitriol, foliol, lagascatriol, linearol, and
      sidol, isolated from Sideritis spp., have been recently identified as
      neuroprotective agents. In this study, the blood brain-barrier permeability
      characteristics of these natural compounds were investigated for the first time
      using in silico and in vitro (RBE4 monocultures and ECV304/C6 co-cultures)
      methods. Computational tools revealed that these diterpenes have a favorable
      permeability profile to pass across the blood brain-barrier. In the RBE4 cell
      model, used for uptake studies, all compounds were taken up in a concentration
      and time-dependent manner. A bidirectional transport of diterpenes was observed
      across the ECV304/C6 co-culture model, with Papp values in the range of 3.7 * 10(
      6) cm/sec and 9.5 * 10(-6) cm/sec for foliol and andalusol, respectively.
      Andalusol and lagascatriol were the most efficiently in being taken up and
      transported across the established blood brain-barrier in vitro model. These
      findings suggest that the investigated compounds from Sideritis spp. may
      predominantly move across the blood brain-barrier by passive diffusion. The
      observations have implications for understanding how CNS-active diterpenes enter
      the brain endothelium and traverse the blood brain-barrier, and thus exert their
      neuroprotective actions.

PMID- 24030292
TI  - Evaluation neointimal coverage in patients with coronary artery aneurysm
      formation after drug-eluting stent implantation by optical coherence tomography.
AB  - The neointimal coverage in patients with coronary artery aneurysms (CAA)
      formation after drug eluting stent (DES) implantation is not clear. Total of 175
      patients who had been implanted DES were identified. Patients were divided into
      the CAA group (n = 31) and non-CAA group (n = 144) based on the results of the
      coronary angiography. The cardiac events including angina and acute myocardial
      infarction were noted, in addition, the neointimal thickness and the frequence of
      strut malapposition and strut uncoverage were noted. A greater proportion of
      incomplete neointimal coverage (17.17 vs. 1.9%, P < 0.001) and malapposition
      struts (18.2 vs. 1.38%, P < 0.001) were observed in the CAA group. 8 patients in
      CAA group underwent OCT examination twice in the period of follow-up. The
      proportion of incomplete neointimal coverage increased significantly as compared
      the second OCT results with the first examination (18.45 vs. 2.66%, P < 0.001).
      Hyperplasia neointimal desquamated from struts and acquired struts incomplete
      neointimal coverage were detected. Patients with CAA had a higher frequency of
      cardiac events including angina pectoris (25.81 vs. 6.25%, P = 0.001) and acute
      myocardial infarction (9.68 vs. 0.13%, P = 0.002) and thrombosis (16.13 vs.
      0.69%, P < 0.001). The longitudinal length of CAA in cardiac event group was
      significantly longer than no cardiac event group (20.0 +/- 9.07 vs. 12.05 +/-
      5.38 mm, P = 0.005). CAA formation after DES implantation frequently associated
      with cardiac events as a result of stent malapposition and incomplete neointimal
      coverage. Acquired incomplete neointimal coverage associated with CAA formation.

PMID- 24030293
TI  - Scanning electron microscopic analysis of polymer damage in drug-eluting stents
      during multiple stenting.
AB  - Polymer damage of drug-eluting stents (DES) during percutaneous coronary
      intervention procedure could be associated with stent restenosis. We assessed the
      damage to the drug-containing polymer of DES during multiple stenting in a
      phantom model by using scanning-electron microscopy (SEM). Unexpanded sirolimus
      eluting stent (SES; n = 15) was delivered through the formerly expanded SES (n =
      15) in a bended polytetrafluoroethylene plastic tube. The stent was
      subcategorized into 4 segments (S), including distal (S1), mid distal (S2), mid
      proximal (S3) and proximal segments (S4), for qualitative SEM assessment. Polymer
      damage, such as detachments, missing or tears, was observed not only in the outer
      surface of the unexpanded stents (100%) but also in the inner surface of the
      formerly expanded stents (100%). There was a significant difference in the
      frequency of polymer damage among the 4 segments in the unexpanded stents (S1 vs.
      S2 vs. S3 vs. S4: 86.7 vs. 80.0 vs. 53.3 vs. 40.0%, p = 0.022) and the formerly
      expanded stents (S1 vs. S2 vs. S3 vs. S4: 80.0 vs. 73.3 vs. 73.3 vs. 40.0%, p =
      0.041). The damage was distributed more frequently in distal part than proximal
      part of either unexpanded stents (S1 vs. S4, p = 0.0079) and the formerly
      expanded stents (S1 vs. S4, p = 0.0079). Delivery of DES through a formerly
      expanded DES could cause damage to drug-containing polymer of the stents.

PMID- 24030294
TI  - The role of contrast enhanced transesophageal echocardiography in the diagnosis
      and in the morphological and functional characterization of acute aortic
      syndromes.
AB  - The aim of this study is to evaluate the role of contrast transesophageal
      echocardiography (cTEE) in the diagnostic characterization of acute aortic
      syndromes (AAS) [aortic dissection, intramural hematoma, penetrating ulcer]. We
      enrolled 66 non-consecutive patients with clinical suspicion of AAS. Standard
      transesophageal echocardiography and cTEE were performed prior to gated-CT
      angiography, which has been assumed as reference standard. cTEE was obtained with
      a single bolus of contrast agent injection. The definitive diagnosis of AAS was
      made in 48 patients by gated-CT angiography: 22 aortic dissections, 15 intramural
      hematomas and 11 penetrating aortic ulcers. Standard TEE and cTEE correctly
      diagnosed AAS in 87 and 100% (P = 0.03) cases respectively. Standard TEE
      correctly diagnosed aortic dissection in 20/22 (91%) and cTEE in 22/22 (100 %) (P
      = 0.5) cases. cTEE was superior than standard TEE in the visualization of false
      lumen entry tear (22/22 vs. 16/22, P = 0.03). Standard TEE correctly diagnosed
      intramural hematoma in 11/15 and cTEE 15/15 (P = 0.12) cases. Microtears were
      identified in 3 patients by cTEE an in 1 patient by standard TEE (P = 0.4). The
      presence of focal contrast enhancement was identified in 4 and 0 patients by cTEE
      and standard TEE respectively (P = 0.06). Both standard and cTEE correctly
      diagnosed penetrating aortic ulcer in 11/11 (100%) (P = 1.0) cases. cTEE provides
      additional value over standard TEE in the diagnosis and in the anatomic and
      functional characterization of AAS.

PMID- 24030297
TI  - Recent research in sports medicine: answers and questions.

PMID- 24030295
TI  - Use of multi-slice computed tomography in patients with chest-pain submitted to
      the emergency department.
AB  - This study evaluates calcium scoring (CS) and computed tomography angiography
      (MSCTA) in patients >50 years with chest-pain submitted to the emergency
      department utilising CS as a "diagnostic filter" upfront. Results of CS and MSCTA
      performed by a 64-slice CT scanner were compared to invasive coronary angiography
      (ICA). 289 consecutive symptomatic patients (185 men, mean age 71.3 +/- 6.4
      years) were included. In patients with CS = 0 (Group I; n = 60) or CS > 400
      (Group III; n = 95) we refrained from MSCTA, whereas patients with CS 1-400
      (Group II; n = 134) underwent subsequent MSCTA. ICA detected significant coronary
      artery disease (CAD) in 162 patients (56.1%; male 98). None of Group I-patients
      showed CAD, but in Group III CAD prevalence increased to 82.1%. In Group II,
      MSCTA correctly identified 177/190 significantly diseased vessel segments.
      Compared to CS alone, our approach increased sensitivity to 98.1% (+1.8%),
      specificity to 82.6% (+27.5%) and negative predictive value (NPV) to 97.2%
      (+5.1%) as well as positive predictive value to 87.8% (+14.6%), respectively.
      Overall DA was 91.3%. Stratification of symptomatic patients into three different
      risk groups according to CS results with concomitantly increasing disease
      prevalence is possible. Zero calcium was found to exclude significant CAD, but
      needs further evaluation. Still server calcifications impair image quality in
      MSCTA. Thus direct referral to ICA might be a reasonable approach in case of high
      CS. In patients with intermediate CS, MSCTA is able to rule out significant CAD
      with a high NPV.

PMID- 24030299
TI  - Doping, ethics, and the sport physician.

PMID- 24030300
TI  - Arkansas' creation and implementation of health and safety legislation utilizing
      Ambrose's requirements for change.

PMID- 24030301
TI  - Joint hypermobility and sport: a review of advantages and disadvantages.
AB  - Joint hypermobility (JH) is a feature observed in several inherited conditions in
      which joints have a range of motion beyond normal limits. Such inherent
      flexibility makes it relatively easy for hypermobile people to perform certain
      physical activities, so this characteristic is particularly convenient for
      certain athletes. However JH also can carry some disadvantages: it has been
      associated to a higher risk of injury and to states of anxiety. The aim of this
      article is to provide an overview of the current evidence concerning the
      advantages and disadvantages of JH in the field of sport. We emphasize the
      importance of detecting JH in athletes in order to intervene appropriately
      through injury prevention programs, and emphasize how inherent anxiety may have a
      negative impact on sporting performance. 

PMID- 24030302
TI  - The accuracy and efficacy of palpation versus image-guided peripheral injections
      in sports medicine.
AB  - There is much debate in the sports medicine community regarding the need for
      image guidance during peripheral joint and soft tissue injections. With the
      increasing availability of office-based ultrasound, many injections that were
      performed previously with a palpation-guided technique are being performed now
      under direct sonographic guidance. However some question the need for such
      guidance, particularly given the increased cost. This manuscript will review the
      reported accuracy and efficacy for various injections commonly performed in a
      sports medicine practice. 

PMID- 24030303
TI  - Training the developing brain, part I: cognitive developmental considerations for
      training youth.
AB  - Based on the fundamental principles of pediatric exercise science and
      developmental physiology, childhood provides a critical window to develop the
      physical readiness of youth through age-related training programs that are
      designed purposely to teach and reinforce fundamental movement skills to enhance
      preparedness for physical activity and sport. Successful implementation of
      developmental programs requires age-related instruction by qualified
      professionals who understand the physical and psychosocial uniqueness of children
      and adolescents. An understanding of the interaction of physical and cognitive
      development is needed to design and implement training strategies that optimize
      training outcomes. Regular training with structured and integrative modalities
      throughout the developmental years as part of physical education, recreation, and
      sports practice can improve athletic performance while reducing common sports
      related injuries and can facilitate the adoption of healthy lifestyles throughout
      adulthood. In this commentary, we outline cognitive developmental considerations
      in youth that may influence the design and implementation of training programs
      aimed at optimizing motor skill development in youth. 

PMID- 24030304
TI  - Current concepts: rotator cuff pathology in athletes--a source of pain or
      adaptive pathology?
AB  - Magnetic resonance imaging (MRI) findings are common in patients and athletes
      with shoulder pain. Historically these anatomic derangements have been thought to
      be the source of the patient's symptoms, and approaches have been focused on
      restoring the anatomy. This manuscript will address three objectives: (1) suggest
      that the approach to rotator cuff disease should be based on the patient's
      history and physical examination, and not necessarily on the anatomic disorders
      apparent on imaging; (2) review the data that supports the contention that
      rotator cuff disease is not the source of pain in the symptomatic shoulder, and
      (3) describe the concept of adaptive pathology. The findings on the MRI in the
      thrower's painful shoulder may be adaptive, and these alterations may be required
      to allow performance at high levels in sport.

PMID- 24030305
TI  - Bilateral hemotympanum in a pair of scuba divers.

PMID- 24030306
TI  - Common injuries and medical problems in singles figure skaters.
AB  - Figure skating continues to increase in popularity as both a recreational and
      competitive sport. Skaters continue to "push the envelope" in perfecting more
      technically difficult skills. With their strenuous training programs, skaters are
      at risk from chronic overuse injuries, which tend to plague singles skaters more
      often than acute injuries. The majority of injuries occur in the lower
      extremities or low back. Figure skaters also are at risk for particular medical
      problems, such as exercise-induced bronchospasm and disordered eating. Sports
      Medicine physicians are sure to encounter figure skaters and their "Sports
      specific problems" in their practice and should be knowledgeable about the common
      maladies that can plague figure skaters. This article reviews the most common
      injuries and medical problems in singles figure skaters. 

PMID- 24030307
TI  - Basketball injuries: caring for a basketball team.
AB  - Basketball is a popular sport in North America and worldwide. Most injuries are
      lower extremity injuries to the ankle and knee. In this article, injuries common
      to basketball and, from our experience, injuries that escape injury surveillance
      systems are discussed from the physician and athletic trainer's perspective. Both
      treatment and prevention of injuries are discussed. 

PMID- 24030308
TI  - Racket sports.
AB  - Tennis may be considered a static and dynamic form of exercise with many well
      demonstrated health benefits. Tennis has similar rates of injury to other
      individual recreational sports and junior competitive sports, without the
      catastrophic risk of contact/collision sports. Classifying tennis players into
      junior and elite categories versus adult recreational players may help in
      outlining volume of play recommendations, exposure risk, and types of injuries.
      Junior and elite players tend to tolerate higher volumes, have more acute and
      lower extremity injuries, and have more serious overuse stress injuries. Adult
      recreational players tend to tolerate lower volumes, have more overuse and upper
      extremity injuries, and more conditions that are degenerative. Many tennis
      players also develop asymmetric musculoskeletal adaptations, which may increase
      risk of specific injury. Tennis-specific evaluations may identify these at-risk
      segments, help guide preventive strategies including technical errors, and assist
      in developing return-to-play recommendations. Other racket sports such as squash,
      badminton, and racquetball have less data available but report both acute and
      traumatic injuries less commonly seen in tennis. 

PMID- 24030309
TI  - Bicycling injuries.
AB  - Bicycling injuries can be classified into bicycle contact, traumatic, and overuse
      injuries. Despite the popularity of cycling, there are few scientific studies
      regarding injuries. Epidemiological studies are difficult to compare due to
      different methodologies and the diverse population of cyclists studied. There are
      only three studies conducted on top level professionals. Ninety-four percent of
      professionals in 1 year have experienced at least one overuse injury. Most
      overuse injuries are mild with limited time off the bike. The most common site of
      overuse injury is the knee, and the most common site of traumatic injury is the
      shoulder, with the clavicle having the most common fracture. Many overuse and
      bicycle contact ailments are relieved with simple bike adjustments. 

PMID- 24030310
TI  - Back to play of athletes after exertional heat stroke.

PMID- 24030311
TI  - Authors' Response to letter to the editor about case report, "Specific exercise
      heat stress protocol for a triathlete's return from exertional heat stroke".

PMID- 24030312
TI  - Efficient treatment allocation in two-way nested designs.
AB  - Cluster randomized and multicenter trials sometimes combine two treatments A and
      B in a factorial design, with conditions such as A, B, A and B, or none. This
      results in a two-way nested design. The usual issue of sample size and power now
      arises for various clinically relevant contrast hypotheses. Assuming a fixed
      total sample size at each level (number of clusters or centers, number of
      patients), we derive the optimal proportion of the total sample to be allocated
      to each treatment arm. We consider treatment assignment first at the highest
      level (cluster randomized trial) and then at the lowest level (multicenter
      trial). We derive the optimal allocation ratio for various sets of clinically
      relevant hypotheses. We then evaluate the efficiency of each allocation and show
      that the popular balanced design is optimal or highly efficient for a range of
      research questions except for contrasting one treatment arm with all other
      treatment arms. We finally present simple equations for the total sample size
      needed to test each effect of interest in a balanced design, as a function of
      effect size, power and type I error alpha. All results are illustrated on a
      cluster-randomized trial on smoking prevention in primary schools and on a
      multicenter trial on lifestyle improvement in general practices. 

PMID- 24030313
TI  - Short-term use of serotonin reuptake inhibitors and risk of upper
      gastrointestinal bleeding.
AB  - OBJECTIVE: The association between selective serotonin receptor inhibitors
      (SSRIs) and risk of upper gastrointestinal bleeding remains controversial.
      Previous studies have generally evaluated the issue for approximately 3 months,
      even though the SSRI-mediated inhibition of platelet serotonin concentrations
      occurs within 7-14 days. The authors explored the risk of upper gastrointestinal
      bleeding after short-term SSRI exposure by a case-crossover design. METHOD: The
      records of psychiatric inpatients with upper gastrointestinal bleeding were
      retrieved from the Taiwan National Health Insurance Database (1998-2009). Rates
      of antidepressant use were compared for case and control periods with time
      windows of 7, 14, and 28 days. The adjusted self-matched odds ratios from a
      conditional logistic regression model were used to determine the association
      between SSRI use and upper gastrointestinal bleeding. RESULTS: A total of 5,377
      patients with upper gastrointestinal bleeding were enrolled. The adjusted odds
      ratio for the risk of upper gastrointestinal bleeding after SSRI exposure was
      1.67 (95% CI=1.23-2.26) for the 7-day window, 1.84 (95% CI=1.42-2.40) for the 14
      day window, and 1.67 (95% CI=1.34-2.08) for the 28-day window. SSRIs with high
      and intermediate, but not low, affinity for serotonin transporter were associated
      with upper gastrointestinal bleeding. An elevated risk of upper gastrointestinal
      bleeding after SSRI exposure was seen in male but not female patients.
      CONCLUSIONS: Short-term SSRI use (7-28 days) is significantly associated with
      upper gastrointestinal bleeding. Gender differences may exist in the relationship
      between SSRI use and upper gastrointestinal bleeding. Physicians should carefully
      monitor signs of upper gastrointestinal bleeding even after short-term exposure
      to SSRIs, as is done with nonsteroidal anti-inflammatory drugs and aspirin.

PMID- 24030314
TI  - Comparative study of high-resolution multifrequency ultrasound of the plantar
      skin in patients with various types of hereditary palmoplantar keratoderma.
AB  - BACKGROUND: High-variable-frequency ultrasound is used as an imaging tool for
      various cutaneous disorders. We utilized this tool in pachyonychia congenita (PC)
      patients, who typically present with plantar hyperkeratosis and often severely
      debilitating pain, compared to patients with epidermolytic palmoplantar
      keratoderma (EPPK) and mal de Meleda (MDM). OBJECTIVE: To ascertain the
      feasibility of ultrasound technology for the diagnosis of PC. METHODS: The study
      included a total of 16 patients, 7 with PC, 5 with EPPK and 4 with MDM, who
      underwent ultrasound examination of the plantar skin with high-resolution
      multifrequency ultrasound equipment. RESULTS: Ultrasound scans performed over the
      proximal and distal plantar foot calluses in PC patients demonstrated hyperechoic
      dots and lines within the epidermis compatible with hyperkeratosis, engorged
      varicose veins in the dermis and an anechoic layer interposed between the
      epidermis and the dermis, corresponding to blister fluid below the calluses. In
      contrast to PC patients, patients with MDM and EPPK demonstrated no blisters.
      CONCLUSION: PC patients, as opposed to a group of patients with MDM and EPPK,
      displayed subepidermal blistering beneath their calluses. This finding may help
      in the diagnosis of PC and in partially explaining plantar pain as part of PC
      symptomatology.

PMID- 24030316
TI  - Progress in improving the lives of patients with albinism in sub-Saharan Africa.

PMID- 24030317
TI  - Niflumic acid reduces histamine-induced interleukin-6 and -8 expression in human
      conjunctival epithelial cells.
AB  - BACKGROUND/AIMS: Histamine remains the main mediator of allergic conjunctivitis
      and induces interleukin (IL)-6 and IL-8 production in human conjunctival
      epithelial cells (HCEC). The purpose of the present study was to determine
      whether histamine induced IL-6 and IL-8 expression in HCEC, and to describe the
      relationship between human calcium-activated chloride channel (hCLCA) 1 activity
      and IL-6 and IL-8 expression. METHODS: HCEC were isolated from human conjunctiva
      and cultured at an air-liquid interface. IL-6 and IL-8 mRNA expression was
      examined by real-time PCR, and IL-6 and IL-8 secretion was measured by ELISA
      after stimulation of HCEC with histamine. RESULTS: Histamine upregulated IL-6 and
      IL-8 expression and IL-6 and IL-8 secretion in a dose-dependent manner in HCEC.
      Niflumic acid (NFA), an hCLCA blocker, reduced histamine-induced IL-6 and IL-8
      expression. CONCLUSION: Histamine-induced IL-6 and IL-8 production could be
      attenuated by NFA, an hCLCA blocker.

PMID- 24030318
TI  - The clinical impact and preventability of ventilator-associated conditions in
      critically ill patients who are mechanically ventilated.
AB  - BACKGROUND: Ventilator-associated conditions (VACs) and infection-related
      ventilator-associated complications (iVACs) are the Centers for Disease Control
      and Prevention's new surveillance paradigms for patients who are mechanically
      ventilated. Little is known regarding the clinical impact and preventability of
      VACs and iVACs and their relationship to ventilator-associated pneumonia (VAP).
      We evaluated these using data from a large, multicenter, quality-improvement
      initiative. METHODS: We retrospectively applied definitions for VAC and iVAC to
      data from a prospective time series study in which VAP clinical practice
      guidelines were implemented in 11 North American ICUs. Each ICU enrolled 30
      consecutive patients mechanically ventilated > 48 h during each of four study
      periods. Data on clinical outcomes and concordance with prevention
      recommendations were collected. VAC, iVAC, and VAP rates over time, the agreement
      (kappa statistic) between definitions, associated morbidity/mortality, and
      independent risk factors for each were determined. RESULTS: Of 1,320 patients,
      139 (10.5%) developed a VAC, 65 (4.9%) developed an iVAC, and 148 (11.2%)
      developed VAP. The agreement between VAP and VAC was 0.18, and between VAP and
      iVAC it was 0.19. Patients who developed a VAC or iVAC had significantly more
      ventilator days, hospital days, and antibiotic days and higher hospital mortality
      than patients who had neither of these conditions. Increased concordance with VAP
      prevention guidelines during the study was associated with decreased VAP and VAC
      rates but no change in iVAC rates. CONCLUSIONS: VACs and iVACs are associated
      with significant morbidity and mortality. Although the agreement between VAC,
      iVAC, and VAP is poor, a higher adoption of measures to prevent VAP was
      associated with lower VAP and VAC rates.

PMID- 24030319
TI  - Sulfite oxidation in the purple sulfur bacterium Allochromatium vinosum:
      identification of SoeABC as a major player and relevance of SoxYZ in the process.
AB  - In phototrophic sulfur bacteria, sulfite is a well-established intermediate
      during reduced sulfur compound oxidation. Sulfite is generated in the cytoplasm
      by the reverse-acting dissimilatory sulfite reductase DsrAB. Many purple sulfur
      bacteria can even use externally available sulfite as a photosynthetic electron
      donor. Nevertheless, the exact mode of sulfite oxidation in these organisms is a
      long-standing enigma. Indirect oxidation in the cytoplasm via adenosine-5'
      phosphosulfate (APS) catalysed by APS reductase and ATP sulfurylase is neither
      generally present nor essential. The inhibition of sulfite oxidation by tungstate
      in the model organism Allochromatium vinosum indicated the involvement of a
      molybdoenzyme, but homologues of the periplasmic molybdopterin-containing SorAB
      or SorT sulfite dehydrogenases are not encoded in genome-sequenced purple or
      green sulfur bacteria. However, genes for a membrane-bound polysulfide reductase
      like iron-sulfur molybdoprotein (SoeABC) are universally present. The catalytic
      subunit of the protein is predicted to be oriented towards the cytoplasm. We
      compared the sulfide- and sulfite-oxidizing capabilities of A. vinosum WT with
      single mutants deficient in SoeABC or APS reductase and the respective double
      mutant, and were thus able to prove that SoeABC is the major sulfite-oxidizing
      enzyme in A. vinosum and probably also in other phototrophic sulfur bacteria. The
      genes also occur in a large number of chemotrophs, indicating a general
      importance of SoeABC for sulfite oxidation in the cytoplasm. Furthermore, we
      showed that the periplasmic sulfur substrate-binding protein SoxYZ is needed in
      parallel to the cytoplasmic enzymes for effective sulfite oxidation in A. vinosum
      and provided a model for the interplay between these systems despite their
      localization in different cellular compartments. 

PMID- 24030321
TI  - Effect of free rotation in polypyridinic ligands of Ru(II) complexes applied in
      light-emitting electrochemical cells.
AB  - In the present work we report the synthesis and the electrochemical,
      photoluminescent and electroluminescent properties of two new Ru(II) complexes
      described by the general formula [Ru(phen)2X](2+), where phen is 1,10
      phenanthroline. The X ligand consists of a 2,2'-bipyridine (bpy) unit substituted
      with two phenyl rings connected to the bpy core through a saturated (Lhydro =
      4,4'-diphenylethyl-2,2'-bipyridine) or a conjugated (LH = 4,4'-bis(alpha-styrene)
      2,2'-bipyridine) carbon-carbon bridge. The photoluminescent spectra indicate
      that, both in solution and solid state, the complex bearing the aliphatic
      substitution bridges exhibits a higher quantum yield and a longer excited state
      lifetime than the fully conjugated complex. The new complexes were used in light
      emitting electrochemical cells (LECs) showing red emission for the complex with
      the Lhydro ligand and no light emission for the complex incorporating the LH
      ligand. This and the photophysical properties make it plausible that for these
      complexes the degree of freedom increases with aliphatic substitution. As a
      consequence, the negative effect of the auto-quenching processes taking place in
      solid LEC devices due to the close molecular packing is limited. When compared
      with the archetype [Ru(phen)3](2+) complex, the complex with aliphatic
      substitution shows better performance in the device supporting the beneficial
      effect of the bulky substitution.

PMID- 24030320
TI  - Pneumococcal conjugate vaccination for older adults: Reply letter to
      Hollingsworth et al.
AB  - Hollingsworth and Isturiz (1) have raised several questions about our earlier
      review of the use of pneumococcal conjugate (PCV) or polysaccharide (PPV) vaccine
      for older adults (i.e., >=65 y of age). (2) They begin by citing two metaanalyses
      published in 2009 and 2013 that concluded that prevention of pneumococcal
      pneumonia could not be demonstrated for PPV. (3)(,) (4) They overlook my earlier
      review of five metaanalyses that was published in 2004. (5) This review showed
      that the study populations in prospective trials of PPV were often not
      representative of the populations of elderly and high-risk adults for whom PPV is
      recommended. Furthermore, the five metaanalyses often omitted clinical trials
      that should have been evaluated, included trials that should have been omitted,
      and frequently miscounted the numbers of subjects and outcome events in the
      individual clinical trials. More important, retrospective sample size
      calculations showed that none of the five metaanalyses included an adequate
      number of person years of observation to rule out false-negative results. The
      numbers speak for themselves and cannot be ignored. Simply put, metaanalyses of
      the PPV clinical trials will never tell us whether the vaccine prevents
      pneumococcal pneumonia or all-cause pneumonia in elderly and high-risk adults,
      and consequently they must be regarded as inconclusive and uninformative. Since
      2004, only one small prospective clinical trial of PPV has been published
      (reviewed in 6). Nothing new has been added to our knowledge of PPV efficacy by
      the more recent metaanalyses. (3)(,) (4) Epidemiologists have reminded us that
      the lack of evidence of PPV efficacy is not evidence of its absence. The
      conclusions of our earlier review still stand. (5.) 

PMID- 24030327
TI  - The immune-stimulating peptide WKYMVm has therapeutic effects against ulcerative
      colitis.
AB  - In this study, we examined the therapeutic effects of an immune-stimulating
      peptide, WKYMVm, in ulcerative colitis. The administration of WKYMVm to dextran
      sodium sulfate (DSS)-treated mice reversed decreases in body weight, bleeding
      score and stool score in addition to reversing DSS-induced mucosa destruction and
      shortened colon. The WKYMVm-induced therapeutic effect against ulcerative colitis
      was strongly inhibited by a formyl peptide receptor (FPR) 2 antagonist, WRWWWW,
      indicating the crucial role of FPR2 in this effect. Mechanistically, WKYMVm
      effectively decreases intestinal permeability by stimulating colon epithelial
      cell proliferation. WKYMVm also strongly decreases interleukin-23 and
      transforming growth factor-beta production in the colon of DSS-treated mice. We
      suggest that the potent immune-modulating peptide WKYMVm and its receptor FPR2
      may be useful in the development of efficient therapeutic agents against chronic
      intestinal inflammatory diseases. 

PMID- 24030331
TI  - Timolol drops causing reversible psoriatic fingernail changes.

PMID- 24030328
TI  - Adolescent relationship violence: help-seeking and help-giving behaviors among
      peers.
AB  - Young people tend to disclose relationship violence experiences to their peers,
      if they disclose at all, yet little is known about the nature and frequency of
      adolescent help-seeking and help-giving behaviors. Conducted within a sample of
      1,312 young people from four New York City high schools, this is the first paper
      to ask adolescent help-givers about the various forms of help they provide and
      among the first to examine how ethnicity and nativity impact help-seeking
      behaviors. Relationship violence victims who had ever disclosed (61%) were more
      likely to choose their friends for informal support. Ethnicity was predictive of
      adolescent disclosure outlets, whereas gender and nativity were not. Latinos were
      significantly less likely than non-Latinos to ever disclose to only friends, as
      compared to disclosing to at least one adult. The likelihood of a young person
      giving help to their friend in a violent relationship is associated with gender,
      ethnicity, and nativity, with males being significantly less likely than females
      to give all forms of help to their friends (talking to their friends about the
      violence, suggesting options, and taking action). Foreign-born adolescents are
      less likely to talk or suggest options to friends in violent relationships. This
      study also found that Latinos were significantly more likely than non-Latinos to
      report taking action with or on behalf of a friend in a violent relationship.
      This research shows that adolescents often rely on each other to address
      relationship violence, underlining the importance of adolescents' receipt of
      training and education on how to support their friends, including when to seek
      help from more formal services. To further understand the valuable role played by
      adolescent peers of victims, future research should explore both which forms of
      help are perceived by the victim to be most helpful and which are associated with
      more positive outcomes.

PMID- 24030332
TI  - Consequences of accidental mitomycin C intraocular injection.

PMID- 24030333
TI  - Ocular syphilis.

PMID- 24030334
TI  - Extraocular extension of uveal melanoma after fine-needle aspiration, vitrectomy,
      and open biopsy.
AB  - IMPORTANCE: The most potentially devastating complication of fine-needle
      aspiration biopsy (FNAB) or open biopsy is extraocular extension of the tumor. In
      this collaborative case series, we report 4 cases of orbital recurrence of
      malignant melanoma as a late complication of biopsy and/or vitrectomy performed
      at referring institutions and then sent to us for evaluation. OBSERVATIONS: Four
      cases of extraocular extension of melanoma are documented following multiple
      procedures including FNAB, vitrectomy, and open biopsies. Three of the patients
      in this series underwent more than 1 FNAB, biopsy, and/or vitrectomy. One
      underwent FNAB only but did not undergo brachytherapy afterward. Most of the
      FNABs, open biopsies, and vitrectomies reported in these cases were not performed
      by us, so details of the technique are not available. From these cases, we are
      not able to determine whether the FNAB or additional invasive procedures caused
      the subsequent extraocular disease or if growth of the tumor into the extraocular
      space occurred independent of or prior to the procedures. CONCLUSIONS AND
      RELEVANCE: Large series of FNAB for uveal melanoma with no extraocular recurrence
      have been reported by multiple experienced centers, and the vast majority of
      these procedures are performed without effect on the patient's prognosis.
      However, the patients described in this series demonstrate that this complication
      is rarely possible.

PMID- 24030335
TI  - Acute bilateral angle closure.

PMID- 24030336
TI  - Deep vein thrombosis following descemet stripping automated endothelial
      keratoplasty.

PMID- 24030337
TI  - Sudden bilateral vision loss and brain infarction following cosmetic hyaluronic
      acid injection.

PMID- 24030338
TI  - Ophthalmic resident education on preventable surgical errors.

PMID- 24030339
TI  - Management of persistent subretinal fluid following retinal detachment repair.

PMID- 24030340
TI  - Inner macular hyperreflectivity demonstrated by optical coherence tomography in
      niemann-pick disease.

PMID- 24030341
TI  - Radiation-related cancer risk associated with radiographic imaging.

PMID- 24030343
TI  - Radiation-related cancer risk associated with radiographic imaging--reply.

PMID- 24030344
TI  - Pathogen safety of long-term treatments for bleeding disorders: (un)predictable
      risks and evolving threats.
AB  - Substantial improvements in the safety of blood and plasma products for the
      management of bleeding disorders have been achieved in recent decades. This has
      led some clinicians to believe that the infectious threat is over and that
      inhibitor formation is the foremost complication of hemophilia therapy. On the
      contrary, elimination of all microbes from blood is difficult, potentially
      impossible, and there are always threats from emerging pathogens. The risk of
      infection transmission is also increasing due to greater exposure to products,
      increasing prophylaxis and high-dose regimens for immune tolerance, and longevity
      of hemophilia patients. Current products can be considered "reasonably safe," but
      pathogen testing is not all-inclusive, and manufacturing and purification
      techniques are often not standardized. Although safer nonplasma-derived products
      are widely used, they are not available for all bleeding disorders, and so there
      is an ongoing need for plasma-derived products. This review will discuss the
      evolving risk from emerging pathogens in the context of the issues described.
      Reducing the risk from emerging infections requires global collaboration to
      devise ways to monitor and continue to improve blood safety. 

PMID- 24030345
TI  - Clinical efficacy and determinants of response to treatment with desmopressin in
      mild hemophilia a.
AB  - Although desmopressin (DDAVP) is considered as the treatment of choice for many
      patients with mild hemophilia A, several aspects of DDAVP therapy remain unclear,
      including the rate and type of response and the molecular determinants of its
      clinical efficacy. To investigate these issues, we retrospectively studied all
      patients with mild hemophilia A followed up at the Parma Hemophilia Center. A
      total of 75 patients were enrolled who underwent a DDAVP test, and out of whom,
      76% (57/75) had a complete or partial response. Response to DDAVP was
      significantly correlated to the patients' age (median age of responders and
      nonresponders: 24 and 18 y, respectively; p = 0.04) and type of mutation (all the
      10 patients with mutations in the promoter region were nonresponders). The median
      basal factor VIII (FVIII):C level was significantly lower in responders than in
      nonresponders (0.14 vs. 0.19 IU/mL, respectively; p = 0.01); this was mainly due
      to nonresponders with promoter region mutations who had higher basal FVIII:C
      levels. During the 12-year follow-up, 82 of 237 (35%) bleeding episodes occurring
      in 27 responder patients were treated with 246 DDAVP infusions with complete or
      partial efficacy in 92% (75/82). Overall, 142 events were managed with 253
      prophylactic DDAVP infusions, which were hemostatically effective in 96% of
      cases. No severe adverse reactions to DDAVP administration were recorded during
      the study period. These results document the safety and efficacy of DDAVP as a
      treatment or prevention of bleeding in patients with mild hemophilia A, also in
      the context of home treatment, and encourage the more widespread use of this
      product. 

PMID- 24030347
TI  - Pulmonary nodules in an immunocompetent child with cat scratch disease.
AB  - We describe an immunocompetent child with cat scratch disease and pulmonary
      nodules as part of her initial presentation. Although pulmonary manifestations
      have been reported with cat scratch disease, nodules are rare in the normal host.

PMID- 24030346
TI  - Incidence and etiology of acute lower respiratory tract infections in
      hospitalized children younger than 5 years in rural Thailand.
AB  - BACKGROUND: Pneumonia remains a leading cause of under-five morbidity and
      mortality globally. Comprehensive incidence, epidemiologic and etiologic data are
      needed to update prevention and control strategies. METHODS: We conducted active,
      population-based surveillance for hospitalized cases of acute lower respiratory
      tract infections (ALRI) among children <5 years of age in rural Thailand. ALRI
      cases were systematically sampled for an etiology study that tested
      nasopharyngeal specimens by polymerase chain reaction; children without ALRI were
      enrolled as controls from outpatient clinics. RESULTS: We identified 28,543
      hospitalized ALRI cases from 2005 to 2010. Among the 49% with chest radiographs,
      76% had findings consistent with pneumonia as identified by 2 study radiologists.
      The hospitalized ALRI incidence rate was 5772 per 100,000 child-years (95%
      confidence interval: 5707, 5837) and was higher in boys versus girls (incidence
      rate ratio 1.38, 95% confidence interval: 1.35-1.41) and in children 6-23 months
      of age versus other age groups (incidence rate ratio 1.76, 95% confidence
      interval: 1.69-1.84). Viruses most commonly detected in ALRI cases were
      respiratory syncytial virus (19.5%), rhinoviruses (18.7%), bocavirus (12.8%) and
      influenza viruses (8%). Compared with controls, ALRI cases were more likely to
      test positive for respiratory syncytial virus, influenza, adenovirus, human
      metapneumovirus and parainfluenza viruses 1 and 3 (P <= 0.01 for all).
      Bloodstream infections, most commonly Streptococcus pneumoniae and nontyphoidal
      Salmonella, accounted for 1.8% of cases. CONCLUSIONS: Our findings underscore the
      high burden of hospitalization for ALRI and the importance of viral pathogens
      among children in Thailand. Interventions targeting viral pathogens coupled with
      improved diagnostic approaches, especially for bacteria, are critical for better
      understanding of ALRI etiology, prevention and control.

PMID- 24030348
TI  - Suspected Buruli ulcer of the face: a case report from Ethiopia.
AB  - We describe the clinical course of a 14-month-old boy with suspected Buruli ulcer
      of the face treated nonsurgically with rifampin and ciprofloxacin. Our patient
      presented with comorbid AIDS, presumed tuberculosis (noncutaneous) and severe
      acute malnutrition. To our knowledge, this is the first report to describe the
      nonsurgical management of facial Buruli ulcer. 

PMID- 24030349
TI  - Leprosy in Colombian children and adolescents.
AB  - While leprosy is not considered a public health problem in Colombia, affected
      children are an important warning sign, demonstrating the challenge of
      controlling the disease. Herein, we report 12 cases of leprosy in patients 5-17
      years of age, summarizing our clinical, micro biological and treatment findings. 

PMID- 24030350
TI  - Comparison of Mycoplasma pneumoniae Infections in asthmatic children versus
      asthmatic adults.
AB  - BACKGROUND: Mycoplasma pneumoniae has been implicated in asthma exacerbations and
      chronic asthma. A 2-year longitudinal study has been conducted to investigate the
      role of M. pneumoniae infections in 168 and 20 hospitalized children and adults,
      respectively, with asthma exacerbation compared with outpatients (88 children and
      48 adults) with chronic asthma (without an exacerbation). The prevalence of
      Chlamydia pneumoniae and respiratory viruses was also assessed in these 2
      populations. METHODS: Lung function testing, blood sampling and microbiological
      testing (polymerase chain reaction, culture and serology) were performed for 256
      children and 68 adults followed by a 7-week, follow-up visit with repeated blood
      sampling for serological testing and phone interviews at 6 and 12 months later.
      RESULTS: M. pneumoniae infection was more prevalent in children with chronic
      asthma (13.6%) compared with children with exacerbation (7.1%), while the reverse
      was true in adults (6.3 vs. 10.0%, respectively). However, these differences were
      not statistically significant. Acute C. pneumoniae infection was identified in
      3.9% of children and 7.4% adults. Children seen for chronic asthma were
      significantly more likely to be infected with C. pneumoniae than children
      hospitalized for an asthma exacerbation. Viruses were the most prevalent
      microorganisms detected in children with an asthma exacerbation. No differences
      in the outcome parameters were identified between M. pneumoniae-infected and
      noninfected patients. CONCLUSIONS: The present study suggests that M. pneumoniae
      does not play a direct role in the pathogenicity of acute or chronic asthma in
      most children.

PMID- 24030351
TI  - Risk for late-onset blood-culture proven sepsis in very-low-birth weight infants
      born small for gestational age: a large multicenter study from the German
      Neonatal Network.
AB  - BACKGROUND: It was the aim of this study to assess whether very-low-birth-weight
      (VLBW) infants born small for gestational age (SGA; birth weight less than 10th
      percentile) are at increased risk for late-onset sepsis. METHODS: This was a
      prospective, multicenter study of the German Neonatal Network including VLBW
      infants from 23 to < 32 weeks post menstrual age born 2009-2011. Outcomes were
      compared between VLBW infants born SGA (birth weight less than tenth percentile
      according to gestational age and gender) and non-SGA infants. The main outcome
      measure was at least 1 episode of late-onset sepsis defined as blood-culture
      confirmed clinical sepsis occurring at >= 72 hours of age. RESULTS: 5886 VLBW
      infants were included. In SGA infants (n = 692), an increased incidence of late
      onset sepsis was noted compared with non-SGA infants (20.1% vs. 14.3 %, P <
      0.001). This difference was only observed among infants with a gestational age of
      27 to < 32 weeks and attributed to sepsis episodes with coagulase-negative
      staphylococci (12.8% vs. 8.3%, P < 0.001). Different treatment modalities (eg
      more frequent use of central venous lines) and longer duration of invasive
      therapies (parenteral nutrition, mechanical ventilation, hospitalization) may
      account for the increased sepsis risk with coagulase-negative staphylococci in
      our SGA cohort. In a multivariate logistic regression analysis, higher
      gestational age [per week; odds ratio (OR): 0.75, 95% confidence interval (CI):
      0.72-0.78, P< 0.0001], treatment with antenatal steroids (OR: 0.7, 95% CI: 0.53
      0.92, P = 0.01), German descendance (OR: 0.76, 95% CI: 0.63-0.91, P = 0.003) and
      prophylaxis with glycopeptide antibiotics (OR: 0.64, 95% CI: 0.47-0.87, P =
      0.005) were shown to be protective against late-onset sepsis. In contrast, longer
      duration of parenteral nutrition (per day; OR: 1.016, 95% CI: 1.011-1.021, P <
      0.0001) and SGA were found to be risk factors (OR: 1.31, 95% CI: 1.02-1.68, P=
      0.03). CONCLUSIONS: SGA contributes to the risk of late-onset sepsis in VLBW
      infants. Future studies are needed to investigate the underlying pathophysiology
      to guide individualized preventive measures in this vulnerable subgroup.

PMID- 24030352
TI  - The clinical burden and predictors of sequelae following invasive meningococcal
      disease in Australian children.
AB  - Of 109 children admitted to a tertiary paediatric hospital with a diagnosis of
      invasive meningococcal disease from 2000-2011, 37.6% (n = 41) developed sequelae;
      for serogroup B, 41.3% developed sequelae. Independent predictors of sequelae
      included: fever >= 39  degrees C on hospital presentation [odds ratio (OR): 4.5;
      P = 0.012] and a diagnosis of septicemia with meningitis compared with septicemia
      alone (OR: 15.5; P < 0.001) and meningitis alone (OR: 7.8; P = 0.002).

PMID- 24030353
TI  - Efficacy and tolerability of intravenous pentamidine isethionate for Pneumocystis
      jiroveci prophylaxis in a pediatric oncology population.
AB  - Cancer therapy routinely requires Pneumocystis jiroveci prophylaxis. In those
      intolerant of trimethoprim/sulfamethoxazole, aerosolized pentamidine is
      convenient and effective. Intravenous pentamidine is often substituted in young
      children but its efficacy remains controversial. In this retrospective study of a
      large pediatric oncology cohort, we confirm intravenous pentamidine to be
      effective and well-tolerated as second-line prophylaxis across all ages. 

PMID- 24030354
TI  - Contrast discrimination by the methods of adjustment and two-alternative forced
      choice.
AB  - Fifty years after the advent of signal-detection theory, some visual scientists
      still adhere to the notion of a high, fixed threshold. Indeed, experienced
      observers are able to deliver consistent settings of thresholds using the method
      of adjustment, but those settings are different from the thresholds obtained with
      two-alternative forced choice (2AFC) procedures. This article illustrates the
      difference by reference to four existing studies of contrast discrimination. All
      four sets of data show clear subthreshold facilitation, but the method of
      adjustment produces a rectilinear characteristic that corresponds to the use of
      different criteria over different ranges of contrast, whereas 2AFC procedures
      produce a curvilinear characteristic with generally lower thresholds. This
      article proposes a theoretical explanation for the difference. 

PMID- 24030355
TI  - Sodium fluoride disrupts DNA methylation of H19 and Peg3 imprinted genes during
      the early development of mouse embryo.
AB  - Sodium fluoride (NaF) is associated with embryonic and fetal development
      abnormalities, but the mechanism by which this occurs is unclear. DNA
      methylation, an important epigenetic reprogramming mechanism, is essential for
      normal embryonic development. Thus, we investigated the effect of NaF on DNA
      methylation in early mouse embryos, as well as mouse sperm and liver using
      bisulfite sequencing and ELISA. Data indicate that H19, a paternally imprinted
      gene, compared to control embryos, was less methylated in 8-cell embryos from
      pregnant mice treated with NaF (100 mg/l) in drinking water for 48 h. Peg3, a
      maternally imprinted gene, and the Line1 repeated sequence were similarly
      methylated in NaF-treated and control embryos. Oral ingestion of NaF for 35 days
      did not significantly change Line1 and genomic global DNA methylation in the
      liver. H19, Rasgrf1, Line1, and genomic global DNA methylation were also similar
      in NaF-treated and control sperm. Female mice mated with NaF-treated male mice
      (35 days) had less methylated H19, but Peg3 was significantly more methylated.
      Line1 was similarly methylated in treated 8-cell embryos, compared to control
      embryos. NaF treatment of male mice before copulation significantly increased the
      expression of H19 in blastocysts, whereas H19 expression was not detected in 8
      cell embryos. Data suggest that NaF may interact directly with the embryo to
      disrupt the maintenance of normal gene imprinting during pregnancy. Long-term NaF
      exposure of males may not directly affect DNA methylation of the sperm and liver,
      but the sperm may signal to early embryos with abnormal gene imprinting.

PMID- 24030356
TI  - Protective role of NecroX-5 against neomycin-induced hair cell damage in
      zebrafish.
AB  - NecroX-5, one of the derivatives of NecroX series compounds, is a mitochondrial
      reactive oxygen species and reactive nitrogen species scavenger that inhibits
      cell death against various kinds of oxidative stresses. The objective of the
      present study was to evaluate the effects of NecroX-5 on neomycin-induced
      ototoxicity in transgenic zebrafish (Brn3C: EGFP). Five days post-fertilization,
      zebrafish larvae were exposed to 125 MUM neomycin and one of the following NecroX
      5 concentrations for 1 h: 10, 25, 50, and 75 MUM. Hair cells within the
      neuromasts of the supraorbital (SO1 and SO2), otic (O1), and occipital (OC1)
      lateral lines were analyzed using fluorescence microscopy (n = 10). The terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay
      and 2-[4-(dimethylamino) styryl]-N-ethylpyridiniumiodide (DASPEI) assay were
      performed for evaluation of apoptosis and mitochondrial damage. Ultrastructural
      changes were evaluated using scanning electron microscopy. NecroX-5 decreased
      neomycin-induced hair cell loss in the neuromasts (NecroX-5 50 MUM: 13.4 +/- 2.0
      cells, 125 MUM neomycin only: 8.1 +/- 1.2 cells; n = 10, P < 0.05) and decreased
      the TUNEL reaction. The ultrastructural analysis showed that the structures of
      mitochondria and hair cells within the neuromasts were preserved in zebrafish
      exposed to 125 MUM neomycin and 50 MUM NecroX-5. NecroX-5 decreased apoptosis and
      mitochondrial damage. In conclusion, NecroX-5 attenuated neomycin-induced hair
      cell loss in zebrafish.

PMID- 24030357
TI  - The visible transmittance and solar modulation ability of VO2 flexible foils
      simultaneously improved by Ti doping: an optimization and first principle study.
AB  - The Mott phase transition compound vanadium dioxide (VO2) shows promise as a
      thermochromic smart material for the improvement of energy efficiency and comfort
      in a number of applications. However, the use of VO2 has been restricted by its
      low visible transmittance (Tvis) and limited solar modulation ability
      (DeltaTsol). Many efforts have been made to improve both of these limitations,
      but progress towards the optimization of one aspect has always come at the
      expense of the other. This paper reports that Ti doping results in the
      improvement of both the Tvis and DeltaTsol of VO2-nanoparticle-derived flexible
      foils to the best levels yet reported. Compared with an undoped VO2 foil, a 15%
      increase (from 46.1% to 53%) in Tvis and a 28% increase (from 13.4% to 17.2%) in
      DeltaTsol are achieved at a Ti doping level of 1.1%, representing the best
      performance reported for similar foils or films prepared using various methods.
      Only a defined doping level of less than 3% is beneficial for simultaneous
      improvement in Tvis and DeltaTsol. First principle calculations suggest that an
      increase in the intrinsic band gap of VO2 (M) and the reduced electron density at
      Fermi level of VO2 (R) cooperate to result in the improvement of DeltaTsol and
      that an enhancement in the optical band gap of VO2 (M) leads to the increase of
      Tvis. 

PMID- 24030358
TI  - Mean--and the reporting of continuous data.

PMID- 24030359
TI  - Basic fibroblast growth factor expression is implicated in mesenchymal stem cells
      response to light-induced retinal injury.
AB  - Neurotrophic factors are involved in neuroprotection and its expression in
      mesenchymal stem cells (MSCs) may change during light-induced retinal injury. In
      this study, neurotrophic factor expression in MSCs was investigated after
      stimulation by supernatants of homogenized retina (SHR) from normal and light
      injured rats. Conditioned media from control MSCs (CM-MSCs), MSCs stimulated by
      normal SHR (CM-NSHR), and MSCs stimulated by light-injured SHR (CM-ISHR) were
      examined regarding their ability to prevent degeneration of retinal explants.
      Basic fibroblast growth factor (bFGF) in MSCs was knockdown by lentivirus
      mediated mRNA interference. Transfected MSCs were stimulated by SHR, and retinal
      preservation was reevaluated in the resultant conditioned media. We detected
      significant up-regulation of bFGF in CM-ISHR, accompanied by superior retinal
      neurotrophic effects in CM-ISHR over CM-NSHR and CM-MSCs. Down-regulation of bFGF
      in MSCs effectively inhibited this protective effect. Adding neutralizing
      antibody against bFGF to CM-ISHR also induced a similar effect. It is thus
      concluded that retinal injury may enhance neurotrophic factor expression in MSCs
      and promote the repair process. bFGF may play a critical role in MSCs' response
      to retinal injury.

PMID- 24030360
TI  - Cannabinoid effects on beta amyloid fibril and aggregate formation, neuronal and
      microglial-activated neurotoxicity in vitro.
AB  - Cannabinoid (CB) ligands have demonstrated neuroprotective properties. In this
      study we compared the effects of a diverse set of CB ligands against beta amyloid
      mediated neuronal toxicity and activated microglial-conditioned media-based
      neurotoxicity in vitro, and compared this with a capacity to directly alter beta
      amyloid (Abeta) fibril or aggregate formation. Neuroblastoma (SH-SY5Y) cells were
      exposed to Abeta1-42 directly or microglial (BV-2 cells) conditioned media
      activated with lipopolysaccharide (LPS) in the presence of the CB1 receptor
      selective agonist ACEA, CB2 receptor-selective agonist JWH-015, phytocannabinoids
      Delta(9)-THC and cannabidiol (CBD), the endocannabinoids 2-arachidonoyl glycerol
      (2-AG) and anandamide or putative GPR18/GPR55 ligands O-1602 and abnormal
      cannabidiol (Abn-CBD). TNF-alpha and nitrite production was measured in BV-2
      cells to compare activation via LPS or albumin with Abeta1-42. Abeta1-42 evoked a
      concentration-dependent loss of cell viability in SH-SY5Y cells but negligible
      TNF-alpha and nitrite production in BV-2 cells compared to albumin or LPS. Both
      albumin and LPS-activated BV-2 conditioned media significantly reduced neuronal
      cell viability but were directly innocuous to SH-SY5Y cells. Of those CB ligands
      tested, only 2-AG and CBD were directly protective against Abeta-evoked SH-SY5Y
      cell viability, whereas JWH-015, THC, CBD, Abn-CBD and O-1602 all protected SH
      SY5Y cells from BV-2 conditioned media activated via LPS. While CB ligands
      variably altered the morphology of Abeta fibrils and aggregates, there was no
      clear correlation between effects on Abeta morphology and neuroprotective
      actions. These findings indicate a neuroprotective action of CB ligands via
      actions at microglial and neuronal cells. 

PMID- 24030362
TI  - Glaucoma: present challenges and future trends.
AB  - The authors indicate four key issues which, in their opinion, represent the most
      stimulating challenges in the field of glaucoma today, and describe the present
      approaches and the developments that can be expected or advised in the near
      future: (1) Glaucoma is often undiagnosed or diagnosed too late. Accurate
      detection is crucial to correctly recognize and treat affected subjects, thus
      reducing the disability and the social burden of the disease. Is glaucoma
      screening advisable and cost-effective? What strategies can be implemented to
      achieve an earlier diagnosis? (2) What role can genetics play in glaucoma
      clinics? (3) What are the fundamentals and the limits of medical hypotensive and
      nonhypotensive treatment of glaucoma today, and what novelties could be
      introduced in the next few years? (4) What are the current and future options for
      glaucoma surgery? Should we aim at reducing aqueous production or at enhancing
      aqueous outflow? What are the success figures and the pros and cons of ab externo
      procedures with external filtration (trabeculectomy, nonpenetrating techniques
      and glaucoma drainage devices) and of ab externo techniques with internal
      filtration (viscocanalostomy and canaloplasty)? Will microinvasive procedures
      ever play a role in the treatment of the disease? These questions and the
      possible future developments in the management of glaucoma are discussed
      critically, based on the current clinical state of the art, on a review of the
      literature, and on an everyday experience in a busy university hospital glaucoma
      service. 

PMID- 24030361
TI  - Transient downregulation of Dab1 protein levels during development leads to
      behavioral and structural deficits: relevance for psychiatric disorders.
AB  - Psychiatric disorders have been hypothesized to originate during development,
      with genetic and environmental factors interacting in the etiology of disease.
      Therefore, developmentally regulated genes have received attention as risk
      modulators in psychiatric diseases. Reelin is an extracellular protein essential
      for neuronal migration and maturation during development, and its expression
      levels are reduced in psychiatric disorders. Interestingly, several perinatal
      insults that increase the risk of behavioral deficits alter Reelin signaling.
      However, it is not known whether a dysfunction in Reelin signaling during
      perinatal stages increases the risk of psychiatric disorders. Here we used a
      floxed dab1 allele to study whether a transient decrease in Dab1, a key component
      of the Reelin pathway, is sufficient to induce behavioral deficits related to
      psychiatric disorders. We found that transient Dab1 downregulation during
      perinatal stages leads to permanent abnormalities of structural layering in the
      neocortex and hippocampus. In contrast, conditional inactivation of the dab1 gene
      in the adult brain does not result in additional layering abnormalities.
      Furthermore, perinatal Dab1 downregulation causes behavior impairments in adult
      mice, such as deficits in memory, maternal care, pre-pulse inhibition, and
      response to cocaine. Some of these deficits were also found to be present in
      adolescence. We also show that D-cycloserine rescues the cognitive deficits
      observed in floxed dab1 mice with layering alterations in the hippocampus and
      neocortex. Our results indicate a causal relation between the downregulation of
      Dab1 protein levels during development and the structural and behavioral deficits
      associated with psychiatric diseases in the adult. 

PMID- 24030363
TI  - Hydroxyisohexyl 3-cyclohexene carboxaldehyde (lyral) in patch test preparations
      under varied storage conditions.
AB  - BACKGROUND: The common practice of preparing patch tests in advance has recently
      been called into question by researchers. It has been established that fragrance
      compounds are volatile and their testing efficacy may be affected by storage
      conditions and preparation. Allergens in fragrance mix I rapidly decrease in
      concentration after preapplication to test chambers. OBJECTIVES: This study aimed
      to investigate the volatility of hydroxyisohexyl 3-cyclohexene carboxaldehyde
      (HICC) in petrolatum when stored in test chambers and to explore the correlation
      between vapor pressure and allergen loss in petrolatum during preparation and
      storage. METHODS: Standardized HICC in petrolatum was prepared and stored in IQ
      Chambers and Finn Chambers with covers at 5 degrees C, 25 degrees C, and 35
      degrees C, and concentration was analyzed at intervals for up to 9 days using gel
      permeation chromatography. RESULTS: Changes in HICC concentrations were not
      statistically significant at 8 hours at 5 degrees C, 25 degrees C, and 35 degrees
      C. After 9 days, HICC concentrations were found to fall approximately 30% when
      stored at 35 degrees C, 10% at 25 degrees C, and less than 5% at 5 degrees C.
      There was no significant difference between IQ and Finn chambers. CONCLUSIONS:
      Hydroxyisohexyl 3-cyclohexene carboxaldehyde concentrations are more stable in
      petrolatum than many other studied fragrance allergens, but HICC is still at risk
      for decreasing concentration when exposed to ambient air or heat for prolonged
      periods.

PMID- 24030364
TI  - Paederus dermatitis featuring chronic contact dermatitis.
AB  - Paederus dermatitis is a distinct variant of acute irritant contact dermatitis
      caused by mucocutaneous contact with the specific toxin of an insect belonging to
      the genus Paederus. It is characterized by the sudden onset of erythema and
      vesiculobullous lesions on exposed skin, with special predilection for the
      periorbital region. Paederus species have been mostly identified in Africa, Asia,
      Australia, and Central/South America. We report a 51-year-old woman who
      experienced 4 recurrences of periorbital erythema and edema in the previous year.
      No consistent etiology could be established at the beginning. Only after taking a
      detailed medical history was it discovered that 1 year before our examination,
      the patient had traveled to Kenya, where she had experienced contact with the
      insect. This fact led us to the diagnosis of Paederus dermatitis. After
      appropriate treatment, a complete regression was observed over a 3-week period. 

PMID- 24030365
TI  - The relevance of 7-day patch test reading.
AB  - BACKGROUND: Patch test readings are usually performed on day 2 (48 hours) and day
      4 (96 hours). However, reports in the literature identify delayed allergy to
      metals, corticosteroids, antibiotics, some preservatives, acrylic and methacrylic
      monomers and p-phenylenediamine. OBJECTIVES: The aim of our study was to identify
      the benefit of performing a day 7 (168 hours) reading to identify relevant late
      positive reactions. PATIENTS/METHODS/MATERIALS: Two hundred three consecutive
      patients were patch tested to the British Society for Cutaneous Allergy standard
      series with additional test series selected according to clinical history and
      applied at the same time. RESULTS: Twenty-six patients (12.8%) had new positive
      reactions on day 7 (168 hours), with 28 relevant positive reactions to 21
      allergens. These included mercury 0.5% (2/26); cobalt chloride 1% (2/26);
      colophony 20% (2/26); disperse blue mix 106/124 1% (2/26); preservatives (4/26)
      that included Methylchloroisothiazolinone/methylisothiazolinone, sodium
      metabisulfite, and diazolidinyl urea; fragrances (7/26); and gentamycin sulfate
      20% (1/26). CONCLUSIONS: These results confirm findings in the literature and
      support the argument for performing a day 7 reading (168 hours) to identify
      relevant late positive reactions.

PMID- 24030366
TI  - Increased expression of gelatinase and caspase activities in the skin of NC/Tnd
      mice: a model for atopic dermatitis.

PMID- 24030367
TI  - Stability of patch test allergens.
AB  - Patch testing is widely used in evaluating suspected contact dermatitis. One
      major component of a quality patch test result is a dependable, predictable
      allergen supply. The allergen needs to be present at a sufficient concentration
      to elicit a reaction in an allergic patient. To better understand the stability
      of patch-test allergens, we completed a systematic review of the literature. We
      found that there is variability in stability among patch-test allergens and that
      although a few have been shown to be stable, many degrade when in storage. In
      most cases, expiration dates should be honored. In addition, allergen panels
      should be prepared as close to the time of patch test application as is possible.

PMID- 24030368
TI  - Patch testing for drugs.
AB  - Adverse drug reactions occur commonly and primarily manifest in a myriad of
      cutaneous eruptions. The use of drug patch testing in the diagnosis of specific
      drug eruptions is increasing; however, a standardized approach to this
      methodology is currently lacking. A review of current literature was performed on
      the available evidence of patch testing for drugs. This review addresses the use
      of patch testing for specific cutaneous adverse drug reactions and for specific
      classes of drugs including antimicrobials, anticonvulsants, antiretrovirals,
      glucocorticoids, and nonsteroidal anti-inflammatory drugs. In addition, the
      approach to performing patch testing to drugs in the clinical arena as well as
      current contraindications for drug patch testing is reviewed. 

PMID- 24030369
TI  - Allergic contact dermatitis in dermatologic surgery: review of common allergens.
AB  - With the growing number of dermatologic surgeries performed each year comes an
      increased potential for patient exposure and sensitization to allergens. Patients
      are exposed to many well-documented allergens in the preoperative,
      intraoperative, and postoperative settings during surgery. Postoperative skin
      complications of allergic contact dermatitis increase health care costs and cause
      patient suffering. Early recognition, diagnosis, and treatment by dermatologic
      surgeons are essential to decrease morbidity related to medically necessary and
      elective cutaneous surgeries. While a specific standard screening panel for
      cutaneous surgery-related allergens is not well established, we propose several
      categories of allergens be strongly considered and tested if a patient is
      suspected of having allergic contact dermatitis in an attempt to reveal pertinent
      allergens and prevent future exposures. 

PMID- 24030370
TI  - Contact alternatives to nickel.
AB  - Allergic contact dermatitis to nickel is a continued health concern
      internationally. Nickel has been found to be the most prevalent and relevant
      allergen in tested populations for the last 3 decades. Furthermore, recent data
      from the North American Contact Dermatitis Group demonstrate positive patch-test
      reactions to nickel at approximately 19.5% of their tested population and a
      significant increase in the positivity rates for the last decade (Dermatitis.
      2013;24:10-21. J Am Acad Dermatol. 1998;38:911-918). Because of the rise in
      allergic contact dermatitis rates to nickel, the American Contact Dermatitis
      Society recognized nickel to be the 2008 Allergen of the Year (J Am Acad
      Dermatol. 2009;60:1067-1069; Dermatitis. 2008;19:3-8). This article recognizes
      the importance of nickel avoidance and highlights potential alternatives. 

PMID- 24030371
TI  - Positive patch test reactions to carba mix and iodopropynyl butylcarbamate: data
      from the North American Contact Dermatitis Group, 1998-2008.
AB  - BACKGROUND: Carba mix (CM) contains 3 chemicals used as accelerators in
      manufacturing of rubber products and agricultural chemicals. Iodopropynyl
      butylcarbamate (IPBC) is a preservative used in industrial and personal care
      products. Potential cross-reactivity between these allergens is unclear.
      OBJECTIVE: This study aimed to determine concomitant reaction rates between CM
      (3% petrolatum [pet]) and IPBC (0.1% pet and/or 0.5% pet). DESIGN: A
      retrospective cross-sectional analysis of data from the North American Contact
      Dermatitis Group from 1998 to 2008 was conducted. Frequencies of positive
      reactions, strength of reactions, and concomitant reaction rates were calculated.
      RESULTS: A total of 25,435 patients were tested. There were 1131 allergic
      reactions to CM and 346 positive reactions to IPBC (either 0.1% pet and/or 0.5%
      pet). Fifty-two patients reacted to both allergens. Most reactions (>69%) were
      doubtful/weakly positive, and of those who reacted to both, most (58%) had
      doubtful and/or weakly positive reactions. There was a statistically significant
      association of concomitant reactions between CM and IPBC; formaldehyde positivity
      was used as control and showed statistically significant concomitant reactions.
      CONCLUSIONS: Overall, concomitant reactions to CM and IPBC were low, and rates
      varied by strength of reaction. True cross-reactivity is unlikely; statistical
      association is likely due to frequent low-grade reactions to irritant patch test
      preparations.

PMID- 24030372
TI  - Captopril-induced DRESS: first reported case confirmed by patch test.

PMID- 24030374
TI  - Patch testing in young children should not be overlooked.

PMID- 24030375
TI  - Howard Maibach, MD.

PMID- 24030376
TI  - Risk factors for parastomal hernia in Japanese patients with permanent colostomy.
AB  - PURPOSE: Although the definitive risk factors for parastomal hernia development
      remain unclear, potential contributing factors have been reported from Western
      countries. The aim of this study was to identify the risk factors for parastomal
      hernia in Japanese patients with permanent colostomies. METHODS: All patients who
      received abdominoperineal resection or total pelvic exenteration at our
      institution between December 2004 and December 2011 were reviewed. Patient
      related, operation-related and postoperative variables were evaluated, in both
      univariate and multivariate analyses, to identify the risk factors for parastomal
      hernia formation. RESULTS: Of the 80 patients who underwent colostomy, 22 (27.5
      %) developed a parastomal hernia during a median follow-up period of 953 days
      (range 15-2792 days). Hernia development was significantly associated with
      increasing patient age and body mass index, a laparoscopic surgical approach and
      the transperitoneal route of colostomy formation. In the multivariate analysis,
      the body mass index (p = 0.022), the laparoscopic approach (p = 0.043) and
      transperitoneal stoma creation (p = 0.021) retained statistical significance.
      CONCLUSIONS: Our findings in Japanese ostomates match those from Western
      countries: a higher body mass index, the use of a laparoscopic approach and a
      transperitoneal colostomy are significant independent risk factors for parastomal
      hernia formation. The precise role of the stoma creation route remains unclear.

PMID- 24030377
TI  - Tes, Licuados, and Capsulas: herbal self-care remedies of Latino/Hispanic
      immigrants for type 2 diabetes.
AB  - PURPOSE: The purpose of this cross-sectional, descriptive study was to explore
      the characteristics of herbal remedy use for diabetes among Latinos/Hispanics
      with type 2 diabetes. METHODS: A convenience sample of 75 Latino/Hispanic adults
      with type 2 diabetes was recruited from community-based settings in North
      Carolina. Data were collected through face-to-face bilingual interviews. Measures
      included a demographic questionnaire; the Traditional, Complementary, and
      Alternative Practices Questionnaire; and biophysical indicators of A1C and body
      mass index. RESULTS: Sixty-nine percent of the sample reported using herbal
      remedies for diabetes self-care. Forty-nine herbal products were identified. The
      most commonly reported products were prickly pear cactus, aloe vera, celery, and
      chayote. The perceived effectiveness of products varied; some said they helped "a
      lot" while others noted the development of side effects. Over three quarters
      (77%) of persons using herbal remedies reported concurrent use with prescribed
      medications. Also, some participants reported skipping or altering the dose of
      diabetes medications when using herbal remedies. Most (77%) reported not
      disclosing herbal remedy use to health care providers. CONCLUSIONS: Diabetes
      educators and other health care providers need to ask Latino/Hispanic clients
      about their use of herbal remedies and become knowledgeable about herbal products
      to provide advice about safety.

PMID- 24030378
TI  - T cells expressing CD123-specific chimeric antigen receptors exhibit specific
      cytolytic effector functions and antitumor effects against human acute myeloid
      leukemia.
AB  - Induction treatments for acute myeloid leukemia (AML) have remained largely
      unchanged for nearly 50 years, and AML remains a disease of poor prognosis.
      Allogeneic hematopoietic cell transplantation can achieve cures in select
      patients and highlights the susceptibility of AML to donor-derived immunotherapy.
      The interleukin-3 receptor alpha chain (CD123) has been identified as a potential
      immunotherapeutic target because it is overexpressed in AML compared with normal
      hematopoietic stem cells. Therefore, we developed 2 chimeric antigen receptors
      (CARs) containing a CD123-specific single-chain variable fragment, in combination
      with a CD28 costimulatory domain and CD3-zeta signaling domain, targeting
      different epitopes on CD123. CD123-CAR-redirected T cells mediated potent
      effector activity against CD123+ cell lines as well as primary AML patient
      samples. CD123 CAR T cells did not eliminate granulocyte/macrophage and erythroid
      colony formation in vitro. Additionally, T cells obtained from patients with
      active AML can be modified to express CD123 CARs and are able to lyse autologous
      AML blasts in vitro. Finally, CD123 CAR T cells exhibited antileukemic activity
      in vivo against a xenogeneic model of disseminated AML. These results suggest
      that CD123 CAR T cells are a promising immunotherapy for the treatment of high
      risk AML.

PMID- 24030379
TI  - Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell
      malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.
AB  - Autologous T cells expressing a CD19-specific chimeric antigen receptor
      (CD19.CAR) are active against B-cell malignancies, but it is unknown whether
      allogeneic CD19.CAR T cells are safe or effective. After allogeneic hematopoietic
      stem cell transplantation (HSCT), infused donor-derived virus-specific T cells
      (VSTs) expand in vivo, persist long term, and display antiviral activity without
      inducing graft-vs-host disease; therefore, we determined whether donor VSTs,
      engineered to express CD19.CAR, retained the characteristics of nonmanipulated
      allogeneic VSTs while gaining antitumor activity. We treated 8 patients with
      allogeneic (donor-derived) CD19.CAR-VSTs 3 months to 13 years after HSCT. There
      were no infusion-related toxicities. VSTs persisted for a median of 8 weeks in
      blood and up to 9 weeks at disease sites. Objective antitumor activity was
      evident in 2 of 6 patients with relapsed disease during the period of CD19.CAR
      VST persistence, whereas 2 patients who received cells while in remission remain
      disease free. In 2 of 3 patients with viral reactivation, donor CD19.CAR-VSTs
      expanded concomitantly with VSTs. Hence CD19.CAR-VSTs display antitumor activity
      and, because their number may be increased in the presence of viral stimuli,
      earlier treatment post-HSCT (when lymphodepletion is greater and the incidence of
      viral infection is higher) or planned vaccination with viral antigens may enhance
      disease control.

PMID- 24030380
TI  - Analysis of the clonal growth and differentiation dynamics of primitive barcoded
      human cord blood cells in NSG mice.
AB  - Human cord blood (CB) offers an attractive source of cells for clinical
      transplants because of its rich content of cells with sustained repopulating
      ability in spite of an apparent deficiency of cells with rapid reconstituting
      ability. Nevertheless, the clonal dynamics of nonlimiting CB transplants remain
      poorly understood. To begin to address this question, we exposed CD34+ CB cells
      to a library of barcoded lentiviruses and used massively parallel sequencing to
      quantify the clonal distributions of lymphoid and myeloid cells subsequently
      detected in sequential marrow aspirates obtained from 2 primary NOD/SCID
      IL2Rgamma(-/-) mice, each transplanted with ~10(5) of these cells, and for
      another 6 months in 2 secondary recipients. Of the 196 clones identified, 68 were
      detected at 4 weeks posttransplant and were often lympho-myeloid. The rest were
      detected later, after variable periods up to 13 months posttransplant, but with
      generally increasing stability throughout time, and they included clones in which
      different lineages were detected. However, definitive evidence of individual
      cells capable of generating T-, B-, and myeloid cells, for over a year, and self
      renewal of this potential was also obtained. These findings highlight the caveats
      and utility of this model to analyze human hematopoietic stem cell control in
      vivo.

PMID- 24030381
TI  - Clinical and biological implications of driver mutations in myelodysplastic
      syndromes.
AB  - Myelodysplastic syndromes (MDS) are a heterogeneous group of chronic
      hematological malignancies characterized by dysplasia, ineffective hematopoiesis
      and a variable risk of progression to acute myeloid leukemia. Sequencing of MDS
      genomes has identified mutations in genes implicated in RNA splicing, DNA
      modification, chromatin regulation, and cell signaling. We sequenced 111 genes
      across 738 patients with MDS or closely related neoplasms (including chronic
      myelomonocytic leukemia and MDS-myeloproliferative neoplasms) to explore the role
      of acquired mutations in MDS biology and clinical phenotype. Seventy-eight
      percent of patients had 1 or more oncogenic mutations. We identify complex
      patterns of pairwise association between genes, indicative of epistatic
      interactions involving components of the spliceosome machinery and epigenetic
      modifiers. Coupled with inferences on subclonal mutations, these data suggest a
      hypothesis of genetic "predestination," in which early driver mutations,
      typically affecting genes involved in RNA splicing, dictate future trajectories
      of disease evolution with distinct clinical phenotypes. Driver mutations had
      equivalent prognostic significance, whether clonal or subclonal, and leukemia
      free survival deteriorated steadily as numbers of driver mutations increased.
      Thus, analysis of oncogenic mutations in large, well-characterized cohorts of
      patients illustrates the interconnections between the cancer genome and disease
      biology, with considerable potential for clinical application. 

PMID- 24030382
TI  - Platelet-derived ERp57 mediates platelet incorporation into a growing thrombus by
      regulation of the alphaIIbbeta3 integrin.
AB  - The platelet protein disulfide isomerase called ERp57 mediates platelet
      aggregation, but its role in thrombus formation is unknown. To determine the
      specific role of platelet-derived ERp57 in hemostasis and thrombosis, we
      generated a megakaryocyte/platelet-specific knockout. Despite normal platelet
      counts and platelet glycoprotein expression, mice with ERp57-deficient platelets
      had prolonged tail-bleeding times and thrombus occlusion times with FeCl3-induced
      carotid artery injury. Using a mesenteric artery thrombosis model, we found
      decreased incorporation of ERp57-deficient platelets into a growing thrombus.
      Platelets lacking ERp57 have defective activation of the alphaIIbbeta3 integrin
      and platelet aggregation. The defect in aggregation was corrected by the addition
      of exogenous ERp57, implicating surface ERp57 in platelet aggregation. Using
      mutants of ERp57, we demonstrate the second active site targets a platelet
      surface substrate to potentiate platelet aggregation. Binding of Alexa 488
      labeled ERp57 to thrombin-activated and Mn(2+)-treated platelets lacking beta3
      was decreased substantially, suggesting a direct interaction of ERp57 with
      alphaIIbbeta3. Surface expression of ERp57 protein and activity in human
      platelets increased with platelet activation, with protein expression occurring
      in a physiologically relevant time frame. In conclusion, platelet-derived ERp57
      directly interacts with alphaIIbbeta3 during activation of this receptor and is
      required for incorporation of platelets into a growing thrombus. 

PMID- 24030383
TI  - Antithrombotic actions of statins involve PECAM-1 signaling.
AB  - Statins are widely prescribed cholesterol-lowering drugs that are a first-line
      treatment of coronary artery disease and atherosclerosis, reducing the incidence
      of thrombotic events such as myocardial infarction and stroke. Statins have been
      shown to reduce platelet activation, although the mechanism(s) through which this
      occurs is unclear. Because several of the characteristic effects of statins on
      platelets are shared with those elicited by the inhibitory platelet adhesion
      receptor PECAM-1 (platelet endothelial cell adhesion molecule-1), we investigated
      a potential connection between the influence of statins on platelet function and
      PECAM-1 signaling. Statins were found to inhibit a range of platelet functional
      responses and thrombus formation in vitro and in vivo. Notably, these effects of
      statins on platelet function in vitro and in vivo were diminished in PECAM-1(-/-)
      platelets. Activation of PECAM-1 signaling results in its tyrosine
      phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2,
      the subsequent binding of phosphoinositol 3-kinase (PI3K), and diminished PI3K
      signaling. Statins resulted in the stimulation of these events, leading to the
      inhibition of Akt activation. Together, these data provide evidence for a
      fundamental role of PECAM-1 in the inhibitory effects of statins on platelet
      activation, which may explain some of the pleiotropic actions of these drugs.

PMID- 24030384
TI  - DNA methylation of Runx1 regulatory regions correlates with transition from
      primitive to definitive hematopoietic potential in vitro and in vivo.
AB  - The transcription factor Runx1 (AML1) is a central regulator of hematopoiesis and
      is required for the formation of definitive hematopoietic stem cells (HSCs).
      Runx1 is alternatively expressed from two promoters: the proximal (P2) prevails
      during primitive hematopoiesis, while the distal (P1) dominates in definitive
      HSCs. Although some transcription factor binding sites and cis-regulatory
      elements have been identified, a mechanistic explanation for the alternative
      promoter usage remains elusive. We investigated DNA methylation of known Runx1
      cis-elements at stages of hematopoietic development in vivo and during
      differentiation of murine embryonic stem cells (ESCs) in vitro. In vivo, we find
      loss of methylation correlated with the primitive to definitive transition at the
      P1 promoter. In vitro, hypomethylation, acquisition of active chromatin
      modifications, and increased transcriptional activity at P1 are promoted by
      direct interaction with HOXB4, a transcription factor that confers definitive
      repopulation status on primitive hematopoietic progenitors. These data
      demonstrate a novel role for DNA methylation in the alternative promoter usage at
      the Runx1 locus and identify HOXB4 as a direct activator of the P1 promoter. This
      epigenetic signature should serve as a novel biomarker of HSC potential in vivo,
      and during ESC differentiation in vitro. 

PMID- 24030385
TI  - Host programmed death ligand 1 is dominant over programmed death ligand 2
      expression in regulating graft-versus-host disease lethality.
AB  - Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, play an important
      role in the maintenance of peripheral tolerance. We explored the role of PD-1
      ligands in regulating graft-versus-host disease (GVHD). Both PD-L1 and PD-L2
      expression were upregulated in the spleen, liver, colon, and ileum of GVHD mice.
      Whereas PD-L2 expression was limited to hematopoietic cells, hematopoietic and
      endothelial cells expressed PD-L1. PD-1/PD-L1, but not PD-1/PD-L2, blockade
      markedly accelerated GVHD-induced lethality. Chimera studies suggest that PD-L1
      expression on host parenchymal cells is more critical than hematopoietic cells in
      regulating acute GVHD. Rapid mortality onset in PD-L1-deficient hosts was
      associated with increased gut T-cell homing and loss of intestinal epithelial
      integrity, along with increased donor T-cell proliferation, activation, Th1
      cytokine production, and reduced apoptosis. Bioenergetics profile analysis of
      proliferating alloreactive donor T-cells demonstrated increased aerobic
      glycolysis and oxidative phosphorylation in PD-L1-deficient hosts. Donor T-cells
      exhibited a hyperpolarized mitochondrial membrane potential, increased superoxide
      production, and increased expression of a glucose transporter in PD-L1-deficient
      hosts. Taken together, these data provide new insight into the differential roles
      of host PD-L1 and PD-L2 and their associated cellular and metabolic mechanisms
      controlling acute GVHD. 

PMID- 24030386
TI  - Highly electronegative LDL from patients with ST-elevation myocardial infarction
      triggers platelet activation and aggregation.
AB  - Platelet activation and aggregation underlie acute thrombosis that leads to ST
      elevation myocardial infarction (STEMI). L5-highly electronegative low-density
      lipoprotein (LDL)-is significantly elevated in patients with STEMI. Thus, we
      examined the role of L5 in thrombogenesis. Plasma LDL from patients with STEMI (n
      = 30) was chromatographically resolved into 5 subfractions (L1-L5) with
      increasing electronegativity. In vitro, L5 enhanced adenosine diphosphate
      stimulated platelet aggregation twofold more than did L1 and induced platelet
      endothelial cell (EC) adhesion. L5 also increased P-selectin expression and
      glycoprotein (GP)IIb/IIIa activation and decreased cyclic adenosine monophosphate
      levels (n = 6, P < .01) in platelets. In vivo, injection of L5 (5 mg/kg) into
      C57BL/6 mice twice weekly for 6 weeks shortened tail bleeding time by 43% (n = 3;
      P < .01 vs L1-injected mice) and increased P-selectin expression and GPIIb/IIIa
      activation in platelets. Pharmacologic blockade experiments revealed that L5
      signals through platelet-activating factor receptor and lectin-like oxidized LDL
      receptor-1 to attenuate Akt activation and trigger granule release and GPIIb/IIIa
      activation via protein kinase C-alpha. L5 but not L1 induced tissue factor and P
      selectin expression in human aortic ECs (P < .01), thereby triggering platelet
      activation and aggregation with activated ECs. These findings indicate that
      elevated plasma levels of L5 may promote thrombosis that leads to STEMI. 

PMID- 24030387
TI  - Mast cells suppress murine GVHD in a mechanism independent of CD4+CD25+
      regulatory T cells.
AB  - To investigate the role of mast cells in hematopoietic cell transplantation, we
      assessed graft-versus-host disease (GVHD) in C57BL/6-Kit(W-sh/W-sh) recipients,
      which virtually lack mast cells, compared with C57BL/6 WT recipients. GVHD was
      severely exacerbated in C57BL/6-Kit(W-sh/W-sh) mice (median survival time = 13 vs
      60 days in wild-type [WT] mice; P < .0001). The increased mortality risk in
      C57BL/6-Kit(W-sh/W-sh) hosts correlated with increased T-cell numbers in lymph
      nodes, liver, and gastrointestinal tract sites, as indicated by bioluminescence
      imaging (P < .001). We did not detect any deficit in the number or function of
      CD4(+)CD25(+) regulatory T cells (Tregs) in C57BL/6-Kit(W-sh/W-sh) mice.
      Furthermore, Tregs were equally effective at reducing GVHD in C57BL/6-Kit(W-sh/W
      sh) recipients compared with WT recipients containing mast cells. Furthermore, we
      found that survival of C57BL/6-Kit(W-sh/W-sh) mice during GVHD was significantly
      improved if the mice were engrafted with bone marrow-derived cultured mast cells
      from WT C57BL/6 mice but not from interleukin (IL)-10-deficient C57BL/6 mice.
      These data indicate that the presence of mast cells can significantly reduce GVHD
      independently of Tregs, by decreasing conventional T-cell proliferation in a
      mechanism involving IL-10. These experiments support the conclusion that mast
      cells can mediate a novel immunoregulatory role during hematopoietic cell
      transplantation. 

PMID- 24030388
TI  - Varenicline, smoking cessation, and neuropsychiatric adverse events.
AB  - OBJECTIVE: In 2009, the U.S. Food and Drug Administration issued a black box
      warning for varenicline regarding neuropsychiatric events. The authors used data
      from randomized controlled trials and from a large Department of Defense (DOD)
      observational study to assess the efficacy and safety of varenicline. METHOD: The
      authors reanalyzed data from the 17 placebo-controlled randomized controlled
      trials (N=8,027) of varenicline conducted by Pfizer, using complete intent-to
      treat person-level longitudinal data to assess smoking abstinence and reports of
      suicidal thoughts and behavior, depression, aggression/agitation, and nausea and
      to compare effects in patients with (N=1,004) and without (N=7,023) psychiatric
      disorders. The authors also analyzed a large DOD data set to compare acute (30
      day and 60-day) rates of neuropsychiatric adverse events in patients receiving
      varenicline or nicotine replacement therapy (N=35,800) and to assess reports of
      anxiety, mood, and psychotic symptoms and disorders, other mental disorders, and
      suicide attempt. RESULTS: In the randomized controlled trials, varenicline
      increased the risk of nausea (odds ratio=3.69, 95% CI=3.03-4.48) but not rates of
      suicidal events, depression, or aggression/agitation. It significantly increased
      the abstinence rate, by 124% compared with placebo and 22% compared with
      bupropion. Having a current or past psychiatric illness increased the risk of
      neuropsychiatric events equally in treated and placebo patients. In the DOD
      study, after propensity score matching, the overall rate of neuropsychiatric
      disorders was significantly lower for varenicline than for nicotine replacement
      therapy (2.28% compared with 3.16%). CONCLUSIONS: This analysis revealed no
      evidence that varenicline is associated with adverse neuropsychiatric events. The
      evidence supports the superior efficacy of varenicline relative to both placebo
      and bupropion, indicating considerable benefit without evidence of risk of
      serious neuropsychiatric adverse events, in individuals with and without a recent
      history of a psychiatric disorder.

PMID- 24030389
TI  - Excited-state spectroscopic investigations of multinuclear complexes based on
      [Ru(bpy)3](2+) moieties connected to 2,2'-bipyridine and 2,2';6',2''-terpyridine
      ligands.
AB  - A number of multinuclear assemblies based on [Ru(bpy)3](2+) photosensitive
      moieties covalently linked to Fe(II), Co(II) or Zn(II) polypyridyl complexes are
      investigated regarding their initial and thermally equilibrated excited states.
      Ground state absorption and vibrational spectroscopic techniques are carried out,
      along with resonance Raman, transient absorption, and time resolved resonance
      Raman measurements. These methods are also supplemented by computational
      modelling. In all systems, the results clearly show that under visible
      irradiation, the substituted bpy linker ligand is involved in the initial (1)MLCT
      excitation of the Ru(II) subunit. For the Ru(II)/Fe(II) linked assemblies,
      absorption due to [Ru(bpy)3](2+) and [Fe(tpy)2](2+) subunits are identified to
      give rise to differing resonance Raman spectra. Transient absorption spectra of
      complexes containing two [Ru(bpy)3](2+) and one [Fe(tpy)2](2+) subunits show a
      strong depletion for the [Fe(tpy)2](2+) absorption peaks, which decay on a much
      faster timescale than the remainder of the transient features. This is consistent
      with a single excitation of the multimetallic assembly, followed by fast
      depletion (<10 ns) of the spectral signal from the bpy ligand bound to the Fe
      subunit. The results are supported by time resolved resonance Raman measurements
      where a number of features assigned to the linker are found at early time-scales.
      Using transient absorption this process can be followed for most complexes.

PMID- 24030390
TI  - Establishing pulmonary and critical care medicine as a subspecialty in China:
      joint statement of the Chinese thoracic society and the American college of chest
      physicians.
AB  - This commentary heralds the recognition in China of a new subspecialty, Pulmonary
      and Critical Care Medicine, and the first national fellowship training pathway in
      any medical specialty. Because of striking environmental health-care similarities
      that existed in the United States, the Chinese medical community decided to model
      the specialty after that in the United States. Because of its expertise in
      educating pulmonary and critical care physicians in the United States, the
      American College of Chest Physicians was chosen by the Chinese Thoracic Society,
      with the approval of the Chinese government, to help with the transformation of
      this new specialty. A work group representing the two societies is collaborating
      to reorganize ICUs within a select group of large teaching hospitals in China and
      to introduce standardized and rigorous training in pulmonary and critical care
      medicine as a national program. 

PMID- 24030391
TI  - Numbers and cytotoxicities of CD3+CD56+ T lymphocytes in peripheral blood of
      patients with acute myeloid leukemia and acute lymphocytic leukemia.
AB  - Recent reports have highlighted the role of cellular immunity in anti-tumor
      defenses. T lymphocytes are known to play important part in anti-cancer immunity.
      The number and function of T lymphocytes are altered in chronic leukemia
      patients. CD3(+)CD56(+) T lymphocytes have also been found to be abnormal in
      cancer patients. We therefore investigated changes in the number and cytotoxicity
      of CD3(+)CD56(+) T lymphocytes in the peripheral blood of acute leukemia (AL)
      patients (excluding acute promyelocytic leukemia), to improve our understanding
      of the role of this T lymphocyte subset. We analyzed CD3(+)CD56(+) T lymphocyte
      numbers and cytotoxicities in healthy controls, AL patients, and AL patients with
      complete remission. Lymphocyte counts were performed in peripheral blood and flow
      cytometry was used to determine cell numbers and cytotoxicities. The absolute
      number of CD3(+)CD56(+) T lymphocytes was increased in AL patients (including
      acute myeloid [AML] and acute lymphocytic leukemia [ALL]) compared with healthy
      controls (P<0.05), but their functioning was significantly reduced (P<0.05). The
      number of CD3(+)CD56(+) T lymphocytes in AML and ALL patients who achieved
      remission following chemotherapy was close to healthy controls (P>0.05), but
      their functioning was still significantly reduced (P<0.05). In addition, the
      number of CD3(+)CD56(+) T lymphocytes increased significantly in AML patients
      with increased peripheral blood white blood cell (WBC) counts, and in ALL
      patients without increased WBCs. These results suggest that cellular immunity may
      respond to AML and ALL, but that lymphocyte cytotoxicity remains impaired.
      Dysfunction of CD3(+)CD56(+) T lymphocytes in AML and ALL patients may contribute
      to the failure of the host immune response against leukemic blasts. 

PMID- 24030392
TI  - A proline-rich loop mediates specific functions of human sialidase NEU4 in SK-N
      BE neuronal differentiation.
AB  - Human sialidase NEU4 long (N4L) is a membrane-associated enzyme that has been
      shown to be localized in the outer mitochondrial membrane. A role in different
      cellular processes has been suggested for this enzyme, such as apoptosis,
      neuronal differentiation and tumorigenesis. However, the molecular bases for
      these roles, not found in any of the other highly similar human sialidases, are
      not understood. We have found that a proline-rich sequence of 81 amino acids,
      unique to NEU4 sequence, contains potential Akt and Erk1 kinase motifs. Molecular
      modeling, based on the experimentally determined three-dimensional structure of
      cytosolic human NEU2, showed that the proline-rich sequence is accommodated in a
      loop, thus preserving the typical beta-barrel structure of sialidases. In order
      to investigate the role of this loop in neuronal differentiation, we obtained SK
      N-BE neuroblastoma cells stably overexpressing either human wild-type N4L or a
      deletion mutant lacking the proline-rich loop. Our results demonstrate that the
      proline-rich region can also enhance cell proliferation and retinoic acid (RA)
      induced neuronal differentiation and it is also involved in NEU4 interaction with
      Akt, as well as in substrate recognition, modifying directly or through the
      interaction with other protein(s) the enzyme specificity toward sialylated
      glycoprotein(s). On the whole, our results suggest that N4L could be a downstream
      component of the PI3K/Akt signaling pathway required for RA-induced
      differentiation of neuroblastoma SK-N-BE cells. 

PMID- 24030393
TI  - Human blood and cardiac stem cells synergize to enhance cardiac repair when
      cotransplanted into ischemic myocardium.
AB  - BACKGROUND: Blood-derived circulatory angiogenic cells (CACs) and resident
      cardiac stem cells (CSCs) have both been shown to improve cardiac function after
      myocardial infarction. The superiority of either cell type has long been an area
      of speculation with no definitive head-to-head trial. In this study, we compared
      the effect of human CACs and CSCs, alone or in combination, on myocardial
      function in an immunodeficient mouse model of myocardial infarction. METHODS AND
      RESULTS: CACs and CSCs were cultured from left atrial appendages and blood
      samples obtained from patients undergoing clinically indicated heart surgery.
      CACs expressed a broader cytokine profile than CSCs, with 3 cytokines in common.
      Coculture of CACs and CSCs further enhanced the production of stromal cell
      derived factor-1alpha and vascular endothelial growth factor (P <= 0.05).
      Conditioned media promoted equivalent vascular networks and CAC recruitment with
      superior effects using cocultured conditioned media. Intramyocardial injection of
      CACs or CSCs alone improved myocardial function and reduced scar burdens when
      injected 1 week after myocardial infarction (P <= 0.05 versus negative controls).
      Cotransplantation of CACs and CSCs together improved myocardial function and
      reduced scar burdens to a greater extent than either stem cell therapy alone (P
      <= 0.05 versus CAC or CSC injection alone). CONCLUSIONS: CACs and CSCs provide
      unique paracrine repertoires with equivalent effects on angiogenesis, stem cell
      migration, and myocardial repair. Combination therapy with both cell types
      synergistically improves postinfarct myocardial function greater than either
      therapy alone. This synergy is likely mediated by the complimentary paracrine
      signatures that promote revascularization and the growth of new myocardium.

PMID- 24030394
TI  - C1q/tumor necrosis factor-related protein-9, a novel adipocyte-derived cytokine,
      attenuates adverse remodeling in the ischemic mouse heart via protein kinase A
      activation.
AB  - BACKGROUND: C1q/tumor necrosis factor-related protein-9 (CTRP9) is a newly
      identified adiponectin paralog with established metabolic regulatory properties.
      However, the role of CTRP9 in postmyocardial infarction remodeling remains
      completely unknown. This study determined whether CTRP9 may regulate cardiac
      remodeling after acute myocardial infarction (AMI) and elucidated the underlying
      mechanisms. METHODS AND RESULTS: Male adult mice were subject to AMI by left
      anterior descending coronary artery ligation or sham surgery and treated with
      saline (vehicle) or globular CTRP9 via peritoneal implant osmotic pumps for 6
      weeks. H9C2 cardiac cell lines were used in vitro for determining underlying
      mechanisms. Adipocyte CTRP9 expression and plasma CTRP9 levels were both
      significantly reduced after AMI. Compared with vehicle, CTRP9 treatment improved
      animal survival rate (P<0.05), restored cardiac function (P<0.05), attenuated
      adverse remodeling (P<0.01), and ameliorated cardiomyocyte apoptosis and fibrosis
      after AMI (P<0.01). Among the multiple antiremodeling molecules determined, AMP
      activated protein kinase, protein kinase A (PKA), and Akt were significantly
      activated in CTRP9-treated heart. Surprisingly, CTRP9 remains cardioprotective in
      mice with cardiomyocyte-specific overexpression of a mutant AMP-activated protein
      kinase alpha2 subunit (AMPK-DN). Additional in vitro experiments demonstrated
      that administration of either PKA inhibitor or PKA-specific small interfering RNA
      virtually abolished the antiapoptotic effect of CTRP9 (P<0.05), whereas
      inhibition of Akt is less effective in blocking CTRP9 cardioprotection. Finally,
      CTRP9 phosphorylates BCL-2-associated agonist of cell death at its multiple
      antiapoptotic sites, an effect blocked by PKA inhibitor. CONCLUSIONS: We
      demonstrate that adipokine CTRP9 attenuates adverse cardiac remodeling after AMI,
      largely via a PKA-dependent pathway.

PMID- 24030395
TI  - Sevoflurane preconditioning attenuates myocardial ischemia/reperfusion injury via
      caveolin-3-dependent cyclooxygenase-2 inhibition.
AB  - BACKGROUND: The inhaled anesthetic sevoflurane has been demonstrated to protect
      against myocardial ischemia/reperfusion (MI/R) injury via mechanisms involving
      AMP-activated protein kinase (AMPK) and caveolin-3 (Cav-3). However, the relative
      contributions of AMPK and Cav-3 to sevoflurane preconditioning (SF-PreCon)
      mediated cardioprotection and their precise underlying mechanisms of action
      remain incompletely understood. METHODS AND RESULTS: SF-PreCon (consisting of 3
      cycles of 15-minute exposure to 2% sevoflurane before 30 minutes of MI) decreased
      MI/R injury in wild-type mice (caspase-3 activity, -29.1%; infarct size, -20.2%;
      and left ventricular end diastolic pressure, -33.8%). In cardiac-specific
      AMPKalpha2 dominant-negative overexpressing mice, the cardioprotective effect of
      SF-PreCon was largely retained (caspase-3 activity, -26.7%; infarct size, -16.7%;
      and left ventricular end-diastolic pressure, -25.9%; P<0.01). In contrast, SF
      PreCon failed to significantly protect Cav-3 knockout mice against MI/R injury
      (P>0.05). SF-PreCon significantly decreased MI/R-induced superoxide generation in
      wild-type (-43.6%) and AMPK dominant-negative overexpressing mice (-35.5%;
      P<0.01) but not in Cav-3 knockout mice. SF-PreCon did not affect nicotinamide
      adenine dinucleotide phosphate oxidase expression but significantly inhibited
      cyclooxygenase-2 expression in wild-type (-38.7%) and AMPK dominant-negative
      overexpressing mice (-35.8%) but not in Cav-3 knockout mice. CONCLUSIONS: We
      demonstrate for the first time SF-PreCon mediates cardioprotection against MI/R
      injury via caveolin-3-dependent cyclooxygenase-2 inhibition and antioxidative
      effects.

PMID- 24030396
TI  - Relationship between mitochondrial matrix volume and cellular volume in response
      to stress and the role of ATP-sensitive potassium channel.
AB  - BACKGROUND: Cardiac myocytes demonstrate significant swelling and associated
      reduced contractility in response to stress that is prevented by the ATP
      sensitive potassium channel opener, diazoxide (DZX) via an unknown mechanism. One
      proposed mechanism of cardioprotection is mitochondrial matrix swelling. To
      establish the relationship between mitochondrial and cellular volume during
      stress, this study examined the effect of DZX on mitochondrial volume. METHODS
      AND RESULTS: Isolated mouse mitochondria were exposed to the following solutions:
      Tyrode, isolation buffer, cardioplegia (CPG)+/-DZX+/-ATP-sensitive potassium
      channel inhibitor, 5-hydroxydecanoate, and metabolic inhibition (MI) +/- DZX +/-
      5-hydroxydecanoate. Mitochondrial volume was measured. DZX resulted in
      significant mitochondrial swelling (P<0.0001 versus Tyrode). MI and CPG resulted
      in significant mitochondrial swelling compared with baseline volume. The addition
      of DZX did not alter the response of mitochondrial volume to CPG (P=0.912) but
      increased swelling in response to MI (P=0.036). The addition of 5
      hydroxydecanoate to MI + DZX or CPG+DZX significantly reduced mitochondrial
      swelling (P<0.003 MI+DZX versus MI + DZX + 5HD; P<0.001 CPG+DZX versus CPG + DZX
      + 5HD). CONCLUSIONS: Both cellular and mitochondrial volume increased during
      exposure to MI and CPG. DZX did not alter mitochondrial volume during CPG;
      however, it was associated with an increase in mitochondrial volume during MI. 5
      Hydroxydecanoate reduced mitochondrial volume during exposure to both stresses
      with DZX, supporting a role for a mitochondrial ATP-sensitive potassium channel
      in the mechanism of cardioprotection by DZX.

PMID- 24030397
TI  - Ethanol promotes arteriogenesis and restores perfusion to chronically ischemic
      myocardium.
AB  - BACKGROUND: Moderate alcohol consumption is known to be cardioprotective compared
      with either heavy drinking or complete abstinence. We assessed the hypothesis
      that ethanol supplementation would improve myocardial function in the setting of
      chronic ischemia. METHODS AND RESULTS: Sixteen male Yorkshire swine underwent
      placement of an ameroid constrictor into the left circumflex artery to induce
      chronic myocardial ischemia. Postoperatively, animals were supplemented with
      either 90 mL of ethanol (EtOH) daily (50%/V, EtOH) or 80 g of sucrose of equal
      caloric value (SUC), serving as controls. Seven weeks after ameroid placement,
      arteriolar density (1.74 +/- 0.210% versus 3.11 +/- 0.368% area of arterioles per
      low-powered field in sucrose (SUC) versus EtOH; P=0.004), myocardial perfusion
      (ratio of blood flow to the at-risk myocardium compared with the normal ventricle
      during demand pacing was 0.585 +/- 0.107 versus 1.08 +/- 0.138 for SUC versus
      EtOH; P=0.014), and microvascular reactivity were significantly increased in
      ethanol-treated animals compared with controls in the at-risk myocardium.
      Analysis of vascular endothelial growth factor and NOTCH pathway signaling
      suggested proneovascular and proliferative activity in the ischemic area. The
      average peak blood alcohol level in the treatment group was 40 +/- 4 mg/dL,
      consistent with levels of moderate drinking in humans. CONCLUSIONS: Ethanol
      supplementation increased arteriolar density and significantly improved
      myocardial perfusion and endothelium-dependent vasorelaxation in chronically
      ischemic myocardium. These findings suggest that, at moderate doses, ethanol
      directly promotes vasculogenesis and improves microvascular function, resulting
      in significant improvements in myocardial perfusion in the setting of chronic
      ischemia.

PMID- 24030398
TI  - Load dependency of right ventricular performance is a major factor to be
      considered in decision making before ventricular assist device implantation.
AB  - BACKGROUND: Left ventricular assist devices (LVADs) provide better outcome than
      biventricular devices, but it is a challenge to predict the impact of LV
      mechanical unloading on postoperative right ventricular (RV) function
      preoperatively. We assessed the load dependency in RV performance before and
      after LVAD implantation aiming to improve preoperative decision making. METHODS
      AND RESULTS: Laboratory, echocardiography, and right heart catheterization data
      collected from 205 patients before LVAD implantation were tested for relationship
      with postoperative RV function. Comparing patients with different time-course of
      RV function after LVAD implantation, we found significant differences (P<0.01) in
      preoperative RV end-diastolic short-/long-axis and long-axis/length-area ratios,
      tricuspid annulus peak systolic velocity, RV peak longitudinal global systolic
      strain rate, systolic pressure gradient between RV and right atrium (DeltaPRV
      RA), tricuspid regurgitation velocity-time integral, and pulmonary arterial
      pressure between patients with and without postoperative RV failure. High
      predictive values for postoperative RV failure were found for end-diastolic short
      /long-axis ratio >= 0.6, tricuspid annulus peak systolic velocity <8 cm/s, and
      peak systolic longitudinal strain rate <0.6/s in patients with maximum DeltaPRV
      RA <35 mm Hg. These parameters also seemed predictive for RV failure in patients
      with tricuspid regurgitation grade >2 and pulmonary arterial pressure <50 mm Hg.
      End-diastolic short-/long-axis ratio <0.6, tricuspid annulus peak systolic
      velocity >= 8 cm/s, and peak systolic longitudinal strain rate >= 0.6 in patients
      with maximum DeltaPRV-RA >= 35 mm Hg showed high predictive values for
      postoperative freedom from RV failure. The RV load adaptation index seemed
      particularly predictive for RV function after LVAD implantation. CONCLUSIONS: RV
      geometry and velocity of contraction before LVAD implantation become more
      predictive for postoperative RV function and can improve decision making before
      VAD implantation if preoperative RV pressure load and tricuspid regurgitation are
      also considered.

PMID- 24030399
TI  - Altered apoptosis-related signaling after cardioplegic arrest in patients with
      uncontrolled type 2 diabetes mellitus.
AB  - BACKGROUND: We investigated the effects of cardioplegic arrest and reperfusion
      (CP/Rep) on myocardial apoptosis and key apoptotic mediators, such as apoptosis
      inducing factor, caspase 3, caspase 8, caspase 9, poly(adenosine diphosphate
      ribose) polymerase, B-cell lymphoma 2 (Bcl-2) family proteins, and protein kinase
      C (PKC), in uncontrolled type 2 diabetic, controlled type 2 diabetic, and
      nondiabetic patients. METHODS AND RESULTS: Right atrial tissue was harvested pre-
      and post-CP/Rep from uncontrolled type 2 diabetic patients (hemoglobin A1c=9.6 +/
      0.25), controlled type 2 diabetic patients (hemoglobin A1c=6.5 +/- 0.15), and
      nondiabetic patients (hemoglobin A1c=5.4 +/- 0.12) undergoing coronary artery
      bypass grafting (n=8/group). Terminal deoxynucleotidyl transferase dUTP nick-end
      labeling staining was used for the identification of apoptotic cells. Total and
      modified apoptosis-inducing factor, Bcl-2 family proteins, phospho-PKC-alpha,
      phospho-PKC-beta1, and poly(adenosine diphosphate-ribose) polymerase were
      quantified by immunoblotting or immunohistochemistry. At baseline, the number of
      apoptotic cells and expression of total apoptosis-inducing factor, Bcl-2, Bak,
      and Bax in the pre-CP/Rep atrial tissue from uncontrolled type 2 diabetic
      patients were significantly increased compared with those of nondiabetic or
      controlled type 2 diabetic patients (P<0.05). After CP/Rep, the amount of
      apoptotic cells, apoptosis-inducing factor, phospho-Bad, phospho-PKC-alpha,
      phospho-PKC-beta1, and cleaved poly(adenosine diphosphate-ribose) polymerase in
      post-CP/Rep atrial tissue were increased in all 3 groups compared with pre
      CP/Rep. These increases after CP/Rep were more pronounced in the uncontrolled
      type 2 diabetic group. In addition, there were significant increases in the
      expression of cleaved caspase 8 and caspase 9 in the basal and post-CP/Rep atrium
      of uncontrolled type 2 diabetic group compared with nondiabetic or controlled
      type 2 diabetic group. CONCLUSIONS: Uncontrolled diabetes mellitus is associated
      with increases in myocardial apoptosis and expression of key apoptosis mediators
      at baseline and in the setting of CP/Rep.

PMID- 24030400
TI  - Toll-like receptor 4-dependent microglial activation mediates spinal cord
      ischemia-reperfusion injury.
AB  - BACKGROUND: Paraplegia continues to complicate thoracoabdominal aortic
      interventions. The elusive mechanism of spinal cord ischemia-reperfusion injury
      has delayed the development of pharmacological adjuncts. Microglia, the resident
      macrophages of the central nervous system, can have pathological responses after
      a variety of insults. This can occur through toll-like receptor 4 (TLR-4) in
      stroke models. We hypothesize that spinal cord ischemia-reperfusion injury after
      aortic occlusion results from TLR-4-mediated microglial activation in mice.
      METHODS AND RESULTS: TLR-4 mutant and wild-type mice underwent aortic occlusion
      for 5 minutes, followed by 60 hours of reperfusion when spinal cords were removed
      for analysis. Spinal cord cytokine production and microglial activation were
      assessed at 6 and 36 hours after surgery. Isolated microglia from mutant and wild
      type mice were subjected to oxygen and glucose deprivation for 24 hours, after
      which the expression of TLR-4 and proinflammatory cytokines was analyzed. Mice
      without functional TLR-4 demonstrated decreased microglial activation and
      cytokine production and had preserved functional outcomes and neuronal viability
      after thoracic aortic occlusion. After oxygen and glucose deprivation, wild-type
      microglia had increased TLR-4 expression and production of proinflammatory
      cytokines. CONCLUSIONS: The absence of functional TLR-4 attenuated neuronal
      injury and microglial activation after thoracic aortic occlusion in mice.
      Furthermore, microglial upregulation of TLR-4 occurred after oxygen and glucose
      deprivation, and the absence of functional TLR-4 significantly attenuated the
      production of proinflammatory cytokines. In conclusion, TLR-4-mediated microglia
      activation in the spinal cord after aortic occlusion is critical in the mechanism
      of paraplegia after aortic cross-clamping and may provide targets for
      pharmacological intervention.

PMID- 24030401
TI  - Impact of wall thickness and saccular geometry on the computational wall stress
      of descending thoracic aortic aneurysms.
AB  - BACKGROUND: Wall stress calculated using finite element analysis has been used to
      predict rupture risk of aortic aneurysms. Prior models often assume uniform
      aortic wall thickness and fusiform geometry. We examined the effects of including
      local wall thickness, intraluminal thrombus, calcifications, and saccular
      geometry on peak wall stress (PWS) in finite element analysis of descending
      thoracic aortic aneurysms. METHODS AND RESULTS: Computed tomographic angiography
      of descending thoracic aortic aneurysms (n=10 total, 5 fusiform and 5 saccular)
      underwent 3-dimensional reconstruction with custom algorithms. For each aneurysm,
      an initial model was constructed with uniform wall thickness. Experimental models
      explored the addition of variable wall thickness, calcifications, and
      intraluminal thrombus. Each model was loaded with 120 mm Hg pressure, and von
      Mises PWS was computed. The mean PWS of uniform wall thickness models was 410 +/-
      111 kPa. The imposition of variable wall thickness increased PWS (481 +/- 126
      kPa, P<0.001). Although the addition of calcifications was not statistically
      significant (506 +/- 126 kPa, P=0.07), the addition of intraluminal thrombus to
      variable wall thickness (359 +/- 86 kPa, P <= 0.001) reduced PWS. A final model
      incorporating all features also reduced PWS (368 +/- 88 kPa, P<0.001). Saccular
      geometry did not increase diameter-normalized stress in the final model (77 +/- 7
      versus 67 +/- 12 kPa/cm, P=0.22). CONCLUSIONS: Incorporation of local wall
      thickness can significantly increase PWS in finite element analysis models of
      thoracic aortic aneurysms. Incorporating variable wall thickness, intraluminal
      thrombus, and calcifications significantly impacts computed PWS of thoracic
      aneurysms; sophisticated models may, therefore, be more accurate in assessing
      rupture risk. Saccular aneurysms did not demonstrate a significantly higher
      normalized PWS than fusiform aneurysms.

PMID- 24030403
TI  - Stroke and outcomes in patients with acute type A aortic dissection.
AB  - BACKGROUND: Stroke is a highly dreaded complication of type A acute aortic
      dissection (TAAAD). However, little data exist on its incidence and association
      with prognosis. METHODS AND RESULTS: We evaluated 2202 patients with TAAAD (mean
      age 62 +/- 14 years, 1487 [67.5%] men) from the International Registry of Acute
      Aortic Dissection to determine the incidence and prognostic impact of stroke in
      TAAAD. Stroke was present at arrival in 132 (6.0%) patients with TAAAD. These
      patients were older (65 +/- 12 versus 62 +/- 15 years; P=0.002) and more likely
      to have hypertension (86% versus 71%; P=0.001) or atherosclerosis (29% versus
      22%; P=0.04) than patients without stroke. Chest pain at arrival was less common
      in patients with stroke (70% versus 82%; P<0.001), and patients with stroke
      presented more often with syncope (44% versus 15%; P<0.001), shock (14% versus
      7%; P=0.005), or pulse deficit (51% versus 29%; P <= 0.001). Arch vessel
      involvement was more frequent among patients with stroke (68% versus 37%;
      P<0.001). They had less surgical management (74% versus 85%; P<0.001). Hospital
      stay was significantly longer in patients with stroke (median 17.9 versus 13.3
      days; P<0.001). In-hospital complications, such as hypotension, coma, and
      malperfusion syndromes, and in-hospital mortality (adjusted odds ratio, 1.62; 95%
      confidence interval, 0.99-2.65) were higher among patients with stroke. Among
      hospital survivors, follow-up mortality was similar between groups (adjusted
      hazard ratio, 1.15; 95% confidence interval, 0.46-2.89). CONCLUSIONS: Stroke
      occurred in >1 of 20 patients with TAAAD and was associated with increased in
      hospital morbidity but not long-term mortality. Whether aggressive early invasive
      interventions will reduce negative outcomes remains to be evaluated in future
      studies.

PMID- 24030402
TI  - KLF4 regulates abdominal aortic aneurysm morphology and deletion attenuates
      aneurysm formation.
AB  - BACKGROUND: KLF4 mediates inflammatory responses after vascular injury/disease;
      however, the role of KLF4 in abdominal aortic aneurysms (AAAs) remains unknown.
      The goals of the present study were to (1) determine the role of KLF4 in
      experimental AAA; and (2) determine the effect of KLF4 on smooth muscle (SM)
      cells in AAAs. METHODS AND RESULTS: KLF4 expression progressively increased at
      days 3, 7, and 14 after aortic elastase perfusion in C57BL/6 mice. Separately,
      loss of a KLF4 allele conferred AAA protection using ERTCre+ KLF4 flx/wt mice in
      the elastase AAA model. In a third set of experiments, SM-specific loss of 1 and
      2 KLF4 alleles resulted in progressively greater protection using novel
      transgenic mice (MYHCre+ flx/flx, flx/wt, and wt/wt) in the elastase AAA model
      compared with control. Elastin degradation, MAC2, and cytokine production (MCP1,
      tumor necrosis factor-alpha, and interleukin-23) were significantly attenuated,
      whereas alpha-actin staining was increased in KLF4 knockout mice versus controls.
      Results were verified in global KLF4 and SM-specific knockout mice using an
      angiotensin II model of aneurysm formation. KLF4 inhibition with siRNA attenuated
      downregulation of SM gene expression in vitro, whereas in vivo studies
      demonstrated that KLF4 binds to promoters of SM genes by chromatin
      immunoprecipitation analysis. Finally, human aortic aneurysms demonstrated
      significantly higher KLF4 expression that was localized to SM cells. CONCLUSIONS:
      KLF4 plays a critical role in aortic aneurysm formation via effects on SM cells.
      These results suggest that KLF4 regulates SM cell phenotypic switching and could
      be a potential therapeutic target for AAA disease.

PMID- 24030404
TI  - Outcomes of patients presenting with acute type A aortic dissection in the
      setting of prior cardiac surgery: an analysis from the International Registry of
      Acute Aortic Dissection.
AB  - BACKGROUND: Prior cardiac surgery (PCS) can complicate the presentation and
      management of patients with type A acute aortic dissection (TAAAD). This report
      from the International Registry of Acute Aortic Dissection examines this
      hypothesis. METHODS AND RESULTS: A total of 352 of 2196 patients with TAAAD (16%)
      enrolled in the International Registry of Acute Aortic Dissection had cardiac
      surgery before dissection, including coronary artery bypass grafting (34%),
      aortic or mitral valve surgery (36%), aortic surgery (42%), and other cardiac
      surgery (16%). Those with PCS were older, had a higher frequency of diabetes
      mellitus, hypertension, and atherosclerosis, and presented later from symptom
      onset to hospital presentation and diagnosis (all P<0.05). In-hospital mortality
      was significantly higher for PCS patients (34% versus 23%; P<0.001). Five-year
      mortality was independently predicted by PCS (hazard ratio [HR], 2.04; 95%
      confidence interval [CI], 1.05-3.95), age >70 years (HR, 2.65; 95% CI, 1.40
      5.05), medical management (HR, 5.10; 95% CI, 2.43-10.71), distal communication
      (HR, 2.64; 95% CI, 1.35-5.14), and coma (HR, 9.50; 95% CI, 2.05-44.05). Among
      patients with PCS, in-hospital (43% medical versus 30% surgical; P=0.033) and
      intermediate-term mortality was higher in patients with medical versus surgical
      management. Propensity-matched analysis revealed significant increase in
      mortality with medical management, but not with PCS. CONCLUSIONS: PCS delays
      presentation, diagnosis, and treatment of TAAAD and is an important adverse risk
      factor for early and intermediate-term mortality. This effect may be because of
      increased medical management in this patient population.

PMID- 24030405
TI  - Reproducible porcine model of thoracic aortic aneurysm.
AB  - BACKGROUND: Thoracic aortic aneurysms (TAAs) develop secondary to abnormal aortic
      extracellular matrix remodeling, resulting in a weakened and dilated aortic wall
      that progressed to rupture if left unattended. Currently, no
      diagnostic/prognostic tests are available for the detection of TAA disease. This
      is largely driven by the lack of a large animal model, which would permit
      longitudinal/mechanistic studies. Accordingly, the objective of the present study
      was to establish a reproducible porcine model of aortic dilatation, which
      recapitulates the structural and biochemical changes observed during human TAA
      development. METHODS AND RESULTS: Descending TAAs were induced in Yorkshire pigs
      (20-25 kg; n=7) through intra-adventitial injections of collagenase (5 mL, 0.35
      mg/mL) and periadventitial application of crystalline CaCl2 (0.5 g). Three weeks
      after TAA induction, aortas were harvested and tissue was collected for
      biochemical and histological measurements. A subset of animals underwent MRI
      preoperatively and at terminal surgery. Results were compared with sham-operated
      controls (n=6). Three weeks after TAA induction, aortic luminal area increased by
      38 +/- 13% (P=0.018 versus control). Aortic structural changes included elastic
      lamellar degradation and decreased collagen content. The protein abundance of
      matrix metalloproteinases 3, 8, 9, and 12 increased in TAA tissue homogenates,
      whereas tissue inhibitors of metalloproteinases 1 and 4 decreased. CONCLUSIONS:
      These data demonstrate aortic dilatation, aortic medial degeneration, and
      alterations in matrix metalloproteinase/tissue inhibitors of metalloproteinase
      abundance, consistent with TAA formation. This study establishes for the first
      time a large animal model of TAA that recapitulates the hallmarks of human
      disease and provides a reproducible test bed for examining diagnostic,
      prognostic, and therapeutic strategies.

PMID- 24030406
TI  - Primary arterial switch operation as a strategy for total correction of Taussig
      Bing anomaly: a 21-year experience.
AB  - BACKGROUND: Studies of the arterial switch operation for Taussig-Bing anomaly
      demonstrate significant rates of reintervention and mortality, particularly after
      initial palliation to delay complete repair. We aimed to describe the long-term
      outcomes of our 21-year practice of single-stage arterial switch operation for
      all patients with Taussig-Bing anomaly. METHODS AND RESULTS: A retrospective
      study was performed, and 43 patients with Taussig-Bing anomaly were identified
      between 1990 and 2011. Median age at arterial switch operation was 7 (range, 2
      192) days, and median operative weight was 3.2 (1.4-6.2) kg. Aortic arch
      obstruction was present in 30 patients (70%). Hospital mortality was 7% (n=3).
      Follow-up was available for 37 hospital survivors at a mean of 8.1 (+/- 6.3)
      years. Late mortality was 2% (n=1). At follow-up, all patients were in New York
      Heart Association functional class I. Freedom from transcatheter or surgical
      reintervention was 73% at 1 year, 64% at 5 years, and 60% at 10 years. Eleven
      patients underwent 13 catheter reinterventions on the pulmonary arteries (n=8) or
      aortic arch (n=5). Seven patients underwent 11 reoperations, including relief of
      right ventricular outflow tract obstruction (n=5), pulmonary arterioplasty (n=3),
      recoarctation repair (n=2), and tricuspid valve repair (n=1). By multivariate
      analysis, a preoperative aortic valve annulus z score of <=-2.5 was associated
      with reintervention (hazard ratio, 7.66 [95% confidence interval, 1.29-45.6],
      P=0.03). CONCLUSIONS: Although reintervention is common, primary correction of
      Taussig-Bing anomaly with arterial switch operation can be achieved in all
      patients with low mortality and good long-term outcomes.

PMID- 24030407
TI  - Impairment of heart rate recovery after peak exercise predicts poor outcome after
      pediatric heart transplantation.
AB  - BACKGROUND: A blunted heart rate recovery (HRR) from peak exercise is associated
      with adverse outcome in adults with ischemic heart disease. We assessed HRR after
      pediatric heart transplantation (HTx) and its prognostic use. METHODS AND
      RESULTS: Between 2004 and 2010 we performed 360 maximal exercise tests (median, 2
      tests/patient; range, 1-7) in 128 children (66 men; age at test, 14 +/- 3 years)
      who received HTx (age, 8.5 +/- 5.1 years) because of cardiomyopathy (66%) or
      congenital heart defects (34%). The change in heart rate from peak exercise to 1
      minute of recovery was measured as HRR and was expressed as Z score calculated
      from reference data obtained in 160 healthy children. HRR was impaired soon after
      HTx (average in first 2 years Z=-1.9 +/- 3.5) but improved afterward (Z=+0.52/y),
      such that HRR Z score normalized in most patients by 6 years after HTx (average,
      0.6 +/- 1.8). A subsequent decline in HRR Z score was noted from 6 years after
      HTx (rate of Z=-0.11/y). After 27 +/- 15 months from the most recent exercise
      test, 19 patients died or were re-heart transplantation. For the follow-up after
      6 years, HRR Z score was the only predictor of death/re-heart transplantation
      (P=0.003). Patients in the lowest quartile of HRR Z score had a much higher 5
      year event rate (event-free rate, 29% versus 84%; hazard ratio, 7.0; P=0.0013).
      CONCLUSIONS: HRR is blunted soon after HTx but normalizes at ~ 6 years,
      potentially as a result of parasympathetic reinnervation of the graft, but then
      declines. This late decline in HRR Z score is associated with worse outcome.

PMID- 24030408
TI  - Surgical palliation strategy does not affect interstage ventricular dysfunction
      or atrioventricular valve regurgitation in children with hypoplastic left heart
      syndrome and variants.
AB  - BACKGROUND: All 3 palliation strategies, Norwood, Sano, and Hybrid, currently
      used for hypoplastic left heart syndrome pose a risk of myocardial injury at
      different times and through different mechanisms. We sought to compare these
      strategies to understand longitudinal differences in interstage ventricular
      dysfunction and their subsequent impact on transplant-free survival and
      atrioventricular valve regurgitation (AVVR) as well as the relationship between
      adverse events and ventricular function. METHODS AND RESULTS: Serial
      echocardiographic reports and clinical data were reviewed for 138 children with
      hypoplastic left heart syndrome who underwent stage I surgical palliation (Sano:
      11; Norwood: 73; Hybrid: 54) between 2004 and 2011. Stage II palliation was
      achieved in 92 (67%) patients (Sano: 7; Norwood: 51; Hybrid: 34). Interstage
      transplant-free survival, ventricular dysfunction, and AVVR were equivalent among
      palliation strategies. Patients with preserved ventricular function had a higher
      rate of transplant-free survival and freedom from AVVR, regardless of palliation
      strategy. Patients who had cardiac arrest, cardiopulmonary resuscitation, or
      extracorporeal membrane oxygenation (adverse events) experienced more transient
      and persistent ventricular dysfunction compared to those without adverse events.
      Surgical palliation strategies were not identified as risk factors for
      ventricular dysfunction or AVVR. CONCLUSIONS: Surgical palliation strategy does
      not affect mortality, interstage ventricular function, or interstage AVVR in
      children with hypoplastic left heart syndrome. Therefore, the different timing
      and mechanisms of myocardial injury among palliation strategies do not affect
      outcomes. Ventricular dysfunction adversely affects transplant-free survival and
      atrioventricular valve function. Adverse events are associated with the
      development of ventricular dysfunction. To improve outcomes, interstage treatment
      should focus on the preservation of ventricular function.

PMID- 24030409
TI  - Correlates of saphenous vein graft hyperplasia and occlusion 1 year after
      coronary artery bypass grafting: analysis from the CASCADE randomized trial.
AB  - BACKGROUND: Intimal hyperplasia of saphenous vein grafts (SVGs) can lead to
      subsequent graft atherosclerosis and occlusion after coronary artery bypass
      grafting (CABG). This study examined whether patient characteristics, anatomic
      factors, and medications are associated with SVG intimal hyperplasia and
      occlusion after CABG. METHODS AND RESULTS: We performed a post hoc analysis of
      the Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) trial, where
      322 grafts were assessed by angiography and 90 grafts were examined by
      intravascular ultrasound at 1 year after CABG. We assessed the following
      correlates for intimal hyperplasia and occlusion: patient characteristics,
      discharge medications, target vessel characteristics, and SVG diameter. At 1
      year, the SVG mean intimal area was 4.3 +/- 2.1 mm(2), and the occlusion rate was
      6.2% (13/209). Independent correlates of hyperplasia were larger SVG diameter
      (1.9 +/- 0.2 mm(2)/mm; P<0.001), hypertension (0.7 +/- 0.3 mm(2); P=0.03), and
      grafting to the right coronary territory (0.6 +/- 0.3 mm(2); P=0.03), whereas
      statin (-0.8 +/- 0.3 mm(2); P=0.01) and beta-blocker use (-1.0 +/- 0.4 mm(2);
      P=0.03) were associated with less hyperplasia. Low target vessel quality was an
      independent correlate of SVG occlusion (odds ratio, 5.2 +/- 3.1; P<0.01).
      CONCLUSIONS: Hypertension, SVG diameter, grafting to the right coronary artery,
      and low quality of the target vessel correlate with the development of SVG
      hyperplasia or occlusion by 1 year after CABG, whereas beta-blockers and statins
      are associated with less SVG disease. These new findings further our
      understanding of SVG remodeling after bypass surgery and may guide future
      research to help prevent post-CABG SVG disease. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00228423.

PMID- 24030410
TI  - Full prescription coverage versus usual prescription coverage after coronary
      artery bypass graft surgery: analysis from the post-myocardial infarction free Rx
      event and economic evaluation (FREEE) randomized trial.
AB  - BACKGROUND: Eliminating out-of-pocket costs for patients after myocardial
      infarction (MI) improves adherence to preventive therapies and reduces clinical
      events. Because adherence to medical therapy is low among patients treated with
      coronary artery bypass graft surgery (CABG), we evaluated the impact of providing
      full prescription coverage to this patient subgroup. METHODS AND RESULTS: The MI
      Free Rx Event and Economic Evaluation (FREEE) trial randomly assigned 5855
      patients with MI to full prescription coverage or usual formulary coverage for
      all statins, beta-blockers, angiotensin-converting enzyme inhibitors, or
      angiotensin receptor blockers. We assessed the impact of full prescription
      coverage on adherence, clinical outcomes, and healthcare costs using adjusted
      models among the 1052 patients who underwent CABG at the index hospitalization
      and 4803 who did not. CABG patients were older and had more comorbid illness
      (P<0.01). After MI, CABG patients were significantly more likely to receive beta
      blockers and statins but were less likely to receive angiotensin-converting
      enzyme inhibitor/angiotensin receptor blocker therapy (P<0.01). Receiving full
      drug coverage increased rates of adherence to all preventative medications after
      CABG (all P<0.05). Full coverage was also associated with nonsignificant
      reductions in the rate of major vascular events or revascularization for patients
      treated with CABG (hazard ratio, 0.91; 95% confidence interval, 0.66-1.25) or
      without CABG (hazard ratio, 0.93; 95% confidence interval, 0.82-1.06), with no
      interaction noted (Pint=NS). After CABG, full prescription coverage significantly
      reduced patient out-of-pocket spending for drugs (P=0.001) without increasing
      overall health expenditures (P=NS). CONCLUSIONS: Eliminating drug copayments
      after MI provides consistent benefits to patients treated with or without CABG,
      leading to increased medication adherence, trends toward improved clinical
      outcomes, and reduced patient out-of-pocket expenses.

PMID- 24030411
TI  - Impact of expeditious management of perioperative myocardial ischemia in patients
      undergoing isolated coronary artery bypass surgery.
AB  - BACKGROUND: To analyze the effect of immediate treatment of perioperative
      myocardial ischemia (PMI) because of early graft failure or incomplete
      revascularization in patients undergoing coronary artery bypass grafting (CABG)
      surgery. METHODS AND RESULTS: Between January 2004 and December 2010, 7461
      patients underwent isolated CABG at our institution. All patients showing
      evidence of PMI (n=399; 5.3% of total) underwent emergent coronary angiography. A
      total of 900 grafts and 1061 distal anastomoses were examined. Two hundred fifty
      five patients had 360 distal anastomoses compromised because of early graft
      failure or incomplete revascularization (ie, abnormal postoperative coronary
      angiogram). Revision CABG or percutaneous coronary intervention was performed in
      130 (51.0%) and 34 (13.3%) patients with abnormal angiograms, respectively.
      Nonsurgical therapy was implemented in the remaining 91 patients (35.7%) with
      abnormal angiograms. One hundred forty-four patients had normal postoperative
      graft-related angiograms. In-hospital mortality was 7.3% and 2.9% in patients
      with and without PMI (P<0.001). In patients with PMI, in-hospital mortality was
      9.4% and 3.5% in patients with abnormal and normal postoperative angiograms,
      respectively (P=0.03). Significant multivariable predictors of in-hospital
      mortality were hemodynamic deterioration, preangiography creatine kinase-MB
      isoenzyme rise >2 * normal, and time interval between primary CABG and coronary
      angiography >30 hours. Five-year survival in patients without PMI (85.7 +/- 0.5%)
      was significantly better than those with PMI and abnormal angiograms (74.9 +/-
      2.9%; P<0.001 log-rank). When in-hospital mortality was excluded, however, this
      difference in midterm survival disappeared (P=0.9). CONCLUSIONS: PMI is
      associated with increased in-hospital mortality in patients undergoing isolated
      CABG. Expeditious management of bypass graft failure results in similar midterm
      survival to nonischemic patients in hospital survivors.

PMID- 24030412
TI  - Outcome and impact of surgery in paradoxical low-flow, low-gradient severe aortic
      stenosis and preserved left ventricular ejection fraction: a cardiac
      catheterization study.
AB  - BACKGROUND: The clinical relevance and management of paradoxical low-flow, low
      gradient aortic stenosis (LFLG-AS) with preserved left ventricular ejection
      fraction remain debated. The aim of this study is to determine the features and
      outcome of LFLG-AS assessed using cardiac catheterization. METHODS AND RESULTS:
      Between 2000 and 2010, 768 patients with preserved left ventricular ejection
      fraction (>50%) and severe AS (valve area <= 1 cm(2)) without other valvular
      disease underwent cardiac catheterization. Mean age was 74 +/- 8 years, 42% were
      women, and 46% had associated coronary artery disease. The prevalence of LFLG
      (indexed left ventricular stroke volume <35 mL/m(2) and mean gradient <40 mm Hg),
      normal flow high gradient, normal flow low gradient, and low flow high gradient
      were 13%, 50%, 22%, and 15%, respectively. Compared with patients with normal
      flow high gradient, those with LFLG were significantly older, with significantly
      reduced systemic arterial compliance and vascular resistances and increased
      valvulo-arterial impedance (all P<0.05). Ten-year survival was reduced in LFLG-AS
      (32 +/- 9%) compared with normal flow high gradient (66 +/- 4%; P=0.0002). After
      adjustment for other risk factors, LFLG-AS was independently associated with
      reduced long-term survival (hazard ratio, 1.85; 95% confidence interval, 1.08
      3.07; P=0.02). However, despite higher operative mortality, patients with LFLG-AS
      undergoing aortic valve replacement seemed to have better long-term survival than
      those managed conservatively (5-year survival rate: 63 +/- 6% versus 38 +/- 15%;
      P=0.007; hazard ratio, 0.23; 95% confidence interval, 0.09-0.59; P=0.002).
      CONCLUSIONS: This large cardiac catheterization-based study reports that the LFLG
      AS entity is not rare and is associated with worse outcome whether treated
      medically or surgically. However, these patients may have better long-term
      survival if treated surgically. Further prospective studies are needed to confirm
      this finding.

PMID- 24030413
TI  - Post-transplant outcomes of children bridged to transplant with the Berlin Heart
      EXCOR Pediatric ventricular assist device.
AB  - BACKGROUND: Recent data suggest that Berlin Heart EXCOR Pediatric (EXCOR)
      ventricular assist device improves waiting list survival for pediatric heart
      transplant candidates. Little is known about their post-transplant outcomes. The
      aim of this analysis was to determine whether there was a difference in early
      survival for children bridged to transplant with EXCOR versus status 1A pediatric
      heart transplant patients not transplanted with ventricular assist device
      support. METHODS AND RESULTS: Pediatric heart transplant patients (n=106) bridged
      to transplantation with EXCOR were compared with a similarly aged cohort (n=1021)
      within the Organ Procurement and Transplant Network (OPTN) database (both cohorts
      from May 2007 to December 2010). In the EXCOR group, 12-month post-transplant
      survival (88.7%) was similar to OPTN patients listed status 1A who were not on
      ventricular assist device support at transplant (89.3%; P=0.85) and significantly
      better than 12-month survival in OPTN patients on extracorporeal membrane
      oxygenation at transplant (60.3%; P<0.001). Rejection (50%) was a significantly
      (P=0.005) higher cause of 12-month post-transplant mortality in the EXCOR
      compared with the OPTN group. Death after transplant was also higher in EXCOR
      patients with congenital heart disease compared with those with cardiomyopathy
      (26.1% versus 7.2%; P=0.02). Post-transplant survival was similar in EXCOR
      patients with >=1 serious adverse event during ventricular assist device support
      as those without an event during support. CONCLUSIONS: The 12-month post
      transplant survival with EXCOR is comparable with overall pediatric heart
      transplant survival and superior to survival after extracorporeal membrane
      oxygenation. Neither adverse events during support nor factors associated with
      mortality during support influence post-transplant survival. Rejection was a
      significantly greater cause of post-transplant mortality in EXCOR than in OPTN
      patients.

PMID- 24030414
TI  - Mitral valve disease in patients with Marfan syndrome undergoing aortic root
      replacement.
AB  - BACKGROUND: Cardiac manifestations of Marfan syndrome include aortic root
      dilation and mitral valve prolapse (MVP). Only scant data exist describing MVP in
      patients with Marfan syndrome undergoing aortic root replacement. METHODS AND
      RESULTS: We retrospectively analyzed data from 166 MFS patients with MVP who were
      enrolled in a prospective multicenter registry of patients who underwent aortic
      root aneurysm repair. Of these 166 patients, 9% had mitral regurgitation (MR)
      grade >2, and 10% had MR grade 2. The severity of MVP and MR was evaluated by
      echocardiography preoperatively and <= 3 years postoperatively. Forty-one
      patients (25%) underwent composite graft aortic valve replacement, and 125
      patients (75%) underwent aortic valve-sparing procedures; both groups had similar
      prevalences of MR grade >2 (P=0.7). Thirty-three patients (20%) underwent
      concomitant mitral valve (MV) intervention (repair, n=29; replacement, n=4),
      including all 15 patients with MR grade >2. Only 1 patient required MV
      reintervention during follow-up (mean clinical follow-up, 31 +/- 10 months).
      Echocardiography performed 21 +/- 13 months postoperatively revealed MR >2 in
      only 3 patients (2%). One early death and 2 late deaths occurred. CONCLUSIONS:
      Although the majority of patients with Marfan syndrome who undergo elective
      aortic root replacement have MVP, only 20% have concomitant MV procedures. These
      concomitant procedures do not seem to increase operative risk. In patients with
      MR grade <= 2 who do not undergo a concomitant MV procedure, the short-term
      incidence of progressive MR is low; however, more follow-up is needed to
      determine whether patients with MVP and MR grade <= 2 would benefit from
      prophylactic MV intervention.

PMID- 24030415
TI  - Late repair of ischemic mitral regurgitation does not prevent left ventricular
      remodeling: importance of timing for beneficial repair.
AB  - BACKGROUND: Ischemic mitral regurgitation (MR) is a frequent complication of
      myocardial infarction associated with left ventricular (LV) dilatation and
      dysfunction, which doubles mortality. At the molecular level, moderate ischemic
      MR is characterized by a biphasic response, with initial compensatory rise in
      prohypertrophic and antiapoptotic signals, followed by their exhaustion. We have
      shown that early MR repair 30 days after myocardial infarction is associated with
      LV reverse remodeling. It is not known whether MR repair performed after the
      exhaustion of compensatory mechanisms is also beneficial. We hypothesized that
      late repair will not result in LV reverse remodeling. METHODS AND RESULTS: Twelve
      sheep underwent distal left anterior descending coronary artery ligation to
      create apical myocardial infarction and implantation of an LV-to-left atrium
      shunt to create standardized moderate volume overload. At 90 days, animals were
      randomized to shunt closure (late repair) versus sham (no repair). LV remodeling
      was assessed by 3-dimensional echocardiography, dP/dt, preload-recruitable stroke
      work, and myocardial biopsies. At 90 days, animals had moderate volume overload,
      LV dilatation, and reduced ejection fraction (all P<0.01 versus baseline, P=NS
      between groups). Shunt closure at 90 days corrected the volume overload
      (regurgitant fraction 6 +/- 5% versus 27 +/- 16% for late repair versus sham,
      P<0.01) but was not associated with changes in LV volumes (end-diastolic volume
      106 +/- 15 versus 110 +/- 22 mL; end-systolic volume 35 +/- 6 versus 36 +/- 6 mL)
      or increases in preload-recruitable stroke work (41 +/- 7 versus 39 +/- 13 mL mm
      Hg) or dP/dt (803 +/- 210 versus 732 +/- 194 mm Hg/s) at 135 days (all P=NS).
      Activated Akt, central in the hypertrophic process, and signal transducer and
      activator of transcription 3 (STAT3), a critical node in the hypertrophic
      stimulus by cytokines, were equally depressed in both groups. CONCLUSIONS: Late
      correction of moderate volume overload after myocardial infarction did not
      improve LV volume or contractility. Upregulation of prohypertrophic intracellular
      pathways was not observed. This contrasts with previously reported study in which
      early repair (30 days) reversed LV remodeling. This suggests a window of
      opportunity to repair ischemic MR after which no beneficial effect on LV is
      observed, despite successful repair.

PMID- 24030416
TI  - Longevity after aortic root replacement: is the mechanically valved conduit
      really the gold standard for quinquagenarians?
AB  - BACKGROUND: The choice of the best conduit for root/ascending disease and its
      impact on longevity remain controversial in quinquagenarians. METHODS AND
      RESULTS: A total of 205 patients (men=155) between 50 and 60 years (mean, 55.7 +/
      2.9 years) received either a stentless porcine xenoroot (n=78) or a mechanically
      valved composite prosthesis (n=127) between February 1998 and July 2011. Of
      these, 166 patients underwent root replacement for aneurysmal disease (porcine:
      39% [n=65]; mechanical: 61% [n=101]; P=0.5), 25 for acute type A aortic
      dissection (porcine: 32% [n=8]; mechanical: 68% [n=17]; P=0.51), and 14 for
      endocarditis/iatrogenic injury involving the aortic root (6.4% [n=5] versus 7.1%
      [n=9]; P=1.0). The predominant aortic valve pathology was stenosis in 19% (n=38),
      regurgitation in 50% (n=102), combined valvular dysfunction in 26% (n=54), and
      normal aortic valve function in 5% (n=11). Concomitant procedures included
      coronary artery bypass grafting (13%), mitral valve repair (7%), and
      partial/complete arch replacement (12%/4%), with no significant differences
      between porcine and mechanical root replacement. Overall hospital mortality was
      7.3%, with no difference between the 2 types of valve prostheses (7.7% for
      porcine and 7.1% for mechanical root replacement; P=1.0). Follow-up averaged 5.4
      +/- 3.7 years (1096 patient-years) and was 100% complete. Freedom from aorta
      related reoperation at 12 years was not statistically different between the
      groups (porcine: 94.9% versus mechanical: 96.1%; P=0.73). Survival was equivalent
      between both groups, with a 5-year survival of 86 +/- 3% (porcine: 88 +/- 4%;
      mechanical: 85 +/- 3%; P=0.96) and a 10-year survival of 76% (porcine: 80 +/- 7%;
      mechanical: 75 +/- 5%; P=0.84). The linearized mortality rate was 3.1%/patient
      year (porcine: 2.9%/patient-year; mechanical: 3.2%/patient-year). CONCLUSIONS: In
      quinquagenerians, long-term survival after stentless porcine xenograft aortic
      root replacement is equivalent to that after a mechanical Bentall procedure.
      These results bring into question the predominance of mechanical composite
      conduits for root replacement in quinquagenerians, particularly in the current
      era of transcatheter valve-in-valve procedures for structural valve
      deterioration.

PMID- 24030417
TI  - Creation of nonischemic functional mitral regurgitation by annular dilatation and
      nonplanar modification in a chronic in vivo swine model.
AB  - BACKGROUND: Mechanisms and treatments of nonischemic functional mitral
      regurgitation (NIMR) are not fully established, in part, because of a lack of
      proper large animal models. We developed a novel technique of NIMR creation in a
      swine model by making multiple small incisions in the mitral annulus. METHODS AND
      RESULTS: Ex vivo experiments using isolated swine hearts (n=10) showed a 15%
      increase in annular area (6.8-7.8 cm(2)) after 16 incisions were made along the
      posterior mitral annulus of a pressurized left ventricle. In an in vivo swine
      model (n=7; 46.4 +/- 2.2 kg), NIMR was created by making fourteen to twenty-six 2
      mm incisions in the atrial aspect of the mitral annulus using a cardioport video
      assisted imaging system in the beating heart. Animals were euthanized at 4 weeks
      (n=4) and 6 weeks (n=3). Three-dimensional (3D) echocardiography was obtained
      before and immediately after NIMR creation and at euthanasia; vena contracta
      area, mitral annular dimension, left ventricular volume, and inter-papillary
      muscle distance were measured. The mitral annular incisions resulted in mild to
      moderate mitral regurgitation and an increased vena contracta area. NIMR creation
      altered mitral valve geometry by decreasing mitral annular nonplanarity and
      increasing annular area, primarily in the anteroposterior dimension. NIMR
      creation did not significantly change left ventricular volume or inter-papillary
      muscle distance. Longer follow-up period did not significantly affect these
      outcomes. CONCLUSIONS: NIMR can successfully be created in a beating heart swine
      model and results in dilatation and 3D changes in mitral annular geometry. This
      model can enhance the experimental validation of new valve repair devices and
      techniques.

PMID- 24030418
TI  - Screening drug-induced arrhythmia [corrected] using human induced pluripotent
      stem cell-derived cardiomyocytes and low-impedance microelectrode arrays.
AB  - BACKGROUND: Drug-induced arrhythmia is one of the most common causes of drug
      development failure and withdrawal from market. This study tested whether human
      induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with a
      low-impedance microelectrode array (MEA) system could improve on industry
      standard preclinical cardiotoxicity screening methods, identify the effects of
      well-characterized drugs, and elucidate underlying risk factors for drug-induced
      arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because
      they possess similar functional characteristics as primary human cardiomyocytes
      and can be generated in unlimited quantities. METHODS AND RESULTS:
      Pharmacological responses of beating embryoid bodies exposed to a comprehensive
      panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC
      CMs to drugs were qualitatively and quantitatively consistent with the reported
      drug effects in literature. Torsadogenic hERG blockers, such as sotalol and
      quinidine, produced statistically and physiologically significant effects,
      consistent with patch-clamp studies, on human embryonic stem cell-derived
      cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were
      identified accurately. Consistent with published studies using animal models,
      early afterdepolarizations and ectopic beats were observed in 33% and 40% of
      embryoid bodies treated with sotalol and quinidine, respectively, compared with
      negligible early afterdepolarizations and ectopic beats in untreated controls.
      CONCLUSIONS: We found that drug-induced arrhythmias can be recapitulated in hiPSC
      CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC
      CM assay is a sensitive, robust, and efficient platform for testing drug
      effectiveness and for arrhythmia screening. This system may hold great potential
      for reducing drug development costs and may provide significant advantages over
      current industry standard assays that use immortalized cell lines or animal
      models.

PMID- 24030419
TI  - Thymosin beta4 increases the potency of transplanted mesenchymal stem cells for
      myocardial repair.
AB  - BACKGROUND: Thymosin beta4 (Tbeta4) has been shown to enhance the survival of
      cultured cardiomyocytes. Here, we investigated whether the cytoprotective effects
      of Tbeta4 can increase the effectiveness of transplanted swine mesenchymal stem
      cells (sMSCs) for cardiac repair in a rat model of myocardial infarction (MI).
      METHODS AND RESULTS: Under hypoxic conditions, cellular damage (lactate
      dehydrogenase leakage), apoptosis (terminal deoxynucleotidyl transferase dUTP
      nick end labelingc cells), and caspase-8 activity were significantly lower,
      whereas B-cell lymphoma-extra large protein expression was significantly higher,
      in sMSCs cultured with Tbeta4 (1 MUg/mL) than in sMSCs cultured without Tbeta4,
      and Tbeta4 also increased sMSC proliferation. For in vivo experiments, animals
      were treated with basal medium (MI: n=6), a fibrin patch (Patch: n=6), a patch
      containing sMSCs (sMSC: n=9), or a patch containing sMSCs and Tbeta4
      (sMSC/Tbeta4: n=11); Tbeta4 was encapsulated in gelatin microspheres to extend
      Tbeta4 delivery. Four weeks after treatment, echocardiographic assessments of
      left-ventricular ejection fraction and fractional shortening were significantly
      better (P<0.05) in sMSC/Tbeta4 animals (left-ventricular ejection fraction=51.7
      +/- 1.1%; fractional shortening=26.7 +/- 0.7%) than in animals from MI (39 +/-
      3%; 19.5 +/- 1.7%) and Patch (43 +/- 1.4%; 21.6 +/- 0.9%) groups. Histological
      assessment of infarct wall thickness was significantly higher (P<0.05) in
      sMSC/Tbeta4 animals (50%, [45%, 80%]) than in animals from MI (25%, [20%, 25%])
      group. Measurements in sMSC (left-ventricular ejection fraction=45 +/- 2.6%;
      fractional shortening=22.9 +/- 1.6%; TH = 43% [25%, 45%]), Patch, and MI animals
      were similar. Tbeta4 administration also significantly increased vascular growth,
      the retention/survival of the transplanted sMSCs, and the recruitment of
      endogenous c-Kit(+) progenitor cells to the infarcted region. CONCLUSIONS:
      Extended-release Tbeta4 administration improves the retention, survival, and
      regenerative potency of transplanted sMSCs after myocardial injury.

PMID- 24030420
TI  - Comparison of transendocardial and intracoronary CD34+ cell transplantation in
      patients with nonischemic dilated cardiomyopathy.
AB  - BACKGROUND: In an open-label blinded study, we compared intracoronary and
      transendocardial CD34(+) cell transplantation in patients with nonischemic
      dilated cardiomyopathy. METHODS AND RESULTS: Of the 40 patients with dilated
      cardiomyopathy, 20 were randomized to receive intracoronary injection and 20
      received transendocardial CD34(+) cell delivery. In both groups, CD34(+) cells
      were mobilized by filgrastim, collected via apheresis, and labeled with
      technetium-99m radioisotope for single-photon emission computed tomographic
      imaging. In the intracoronary group, cells were injected intracoronarily in the
      artery supplying segments of greater perfusion defect on myocardial perfusion
      scintigraphy. In the transendocardial group, electroanatomic mapping was used to
      identify viable but dysfunctional myocardium, and transendocardial cell
      injections were performed. Nuclear single-photon emission computed tomographic
      imaging for quantification of myocardial retention was performed 18 hours
      thereafter. At baseline, groups did not differ in age, sex, left ventricular
      ejection fraction, or N-terminal pro-brain natriuretic peptide levels. The number
      of CD34(+) cells was also comparable (105 +/- 31 * 10(6) in the transendocardial
      group versus 103 +/- 27 * 10(6) in the intracoronary group, P=0.62). At 18 hours
      after procedure, myocardial retention was higher in the transendocardial group
      (19.2 +/- 4.8%) than in the intracoronary group (4.4 +/- 1.2%, P<0.01). At 6
      months, left ventricular ejection fraction improved more in the transendocardial
      group (+8.1 +/- 4.3%) than in the intracoronary group (+4.2 +/- 2.3%, P=0.03).
      The same pattern was observed for the 6-minute walk test distance (+125 +/- 33 m
      in the transendocardial group versus +86 +/- 13 m in the intracoronary group,
      P=0.03) and N-terminal pro-brain natriuretic peptide (-628 +/- 211 versus -315 +/
      133 pg/mL, P=0.04). CONCLUSIONS: In patients with dilated cardiomyopathy,
      transendocardial CD34(+) cell transplantation is associated with higher
      myocardial retention rates and greater improvement in ventricular function, N
      terminal pro-brain natriuretic peptide, and exercise capacity compared with
      intracoronary route. CLINICAL TRIAL REGISTRATION URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT01350310.

PMID- 24030421
TI  - Tetrahydrobiopterin determines vascular remodeling through enhanced endothelial
      cell survival and regeneration.
AB  - BACKGROUND: Endothelial cell (EC) survival and regeneration are important
      determinants of the response to vascular injury that leads to neointimal
      hyperplasia and accelerated atherosclerosis. Nitric oxide (NO) is a key regulator
      of EC and endothelial progenitor cell function, but the pathophysiological
      mechanisms that regulate endothelial NO synthase in endothelial regeneration
      remain unclear. METHODS AND RESULTS: Endothelium-targeted overexpression of GTP
      cyclohydrolase (GCH) I increased levels of the endothelial NO synthase cofactor,
      tetrahydrobiopterin, in an EC-specific manner and reduced neointimal hyperplasia
      in experimental vein grafts in GCH/apolipoprotein E-knockout mice. These effects
      were mediated through enhanced donor-derived survival and recipient-derived
      repopulation of GCH transgenic ECs, revealed by tracking studies in Tie2-LacZ/GCH
      Tg/apolipoprotein E-knockout recipient mice or donor grafts, respectively.
      Endothelial GCH overexpression increased endothelial NO synthase coupling and
      enhanced the proliferative capacity of ECs and circulating endothelial progenitor
      cell numbers after vascular injury. CONCLUSIONS: These observations indicate that
      endothelial tetrahydrobiopterin availability modulates neointimal hyperplasia
      after vascular injury via accelerated EC repopulation and growth. Targeting
      tetrahydrobiopterin-dependent endothelial NO synthase regulation in the
      endothelium is a rational therapeutic target to enhance endothelial regeneration
      and reduce neointimal hyperplasia in vascular injury states.

PMID- 24030422
TI  - Spatially oriented, temporally sequential smooth muscle cell-endothelial
      progenitor cell bi-level cell sheet neovascularizes ischemic myocardium.
AB  - BACKGROUND: Endothelial progenitor cells (EPCs) possess robust therapeutic
      angiogenic potential, yet may be limited in the capacity to develop into fully
      mature vasculature. This problem might be exacerbated by the absence of a
      neovascular foundation, namely pericytes, with simple EPC injection. We
      hypothesized that coculturing EPCs with smooth muscle cells (SMCs), components of
      the surrounding vascular wall, in a cell sheet will mimic the native spatial
      orientation and interaction between EPCs and SMCs to create a supratherapeutic
      angiogenic construct in a model of ischemic cardiomyopathy. METHODS AND RESULTS:
      Primary EPCs and SMCs were isolated from Wistar rats. Confluent SMCs topped with
      confluent EPCs were spontaneously detached from the Upcell dish to create an SMC
      EPC bi-level cell sheet. A rodent ischemic cardiomyopathy model was created by
      ligating the left anterior descending coronary artery. Rats were then immediately
      divided into 3 groups: cell-sheet transplantation (n=14), cell injection (n=12),
      and no treatment (n=13). Cocultured EPCs and SMCs stimulated an abundant release
      of multiple cytokines in vitro. Increased capillary density and improved blood
      perfusion in the borderzone elucidated the significant in vivo angiogenic
      potential of this technology. Most interestingly, however, cell fate-tracking
      experiments demonstrated that the cell-sheet EPCs and SMCs directly migrated into
      the myocardium and differentiated into elements of newly formed functional
      vasculature. The robust angiogenic effect of this cell sheet translated to
      enhanced ventricular function as demonstrated by echocardiography. CONCLUSIONS:
      Spatially arranged EPC-SMC bi-level cell-sheet technology facilitated the natural
      interaction between EPCs and SMCs, thereby creating structurally mature,
      functional microvasculature in a rodent ischemic cardiomyopathy model, leading to
      improved myocardial function.

PMID- 24030423
TI  - Preserving prostaglandin E2 level prevents rejection of implanted allogeneic
      mesenchymal stem cells and restores postinfarction ventricular function.
AB  - BACKGROUND: Allogeneic mesenchymal stem cells (MSCs) were immunoprivileged early
      after cardiac implantation and improved heart function in preclinical and
      clinical studies. However, long-term preclinical studies demonstrated that
      allogeneic MSCs lost their immunoprivilege and were rejected in the injured
      myocardium, resulting in recurrent ventricular dysfunction. This study identifies
      some of the mechanisms responsible for the immune switch in MSCs and suggests a
      new treatment to maintain immunoprivilege and preserve heart function. METHODS
      AND RESULTS: Rat MSC immunoprivilege was mediated by prostaglandin E2 (PGE2)
      induced secretion of 2 critical chemokines, CCL12 and CCL5. These chemokines
      stimulated the chemoattraction of T cells toward MSCs, suppressed cytotoxic T
      cell proliferation, and induced the production of T regulatory cells. MSCs
      treated with 5-azacytidine for 24 hours differentiated into myogenic cells after
      2 weeks, which was associated with decreased PGE2 and chemokine production and
      the loss of immunoprivilege. Treatment of differentiated MSCs with PGE2 restored
      chemokine levels and preserved MSC immunoprivilege. In a rat myocardial
      infarction model, allogeneic MSCs (3 * 10(6) cells/rat) were injected into the
      infarct region with or without a biodegradable hydrogel that slowly released
      PGE2. Five weeks later, the transplanted MSCs expressed myogenic lineage markers
      and were rejected in the control group, but in the PGE2-treated group, the
      transplanted cells survived and heart function improved. CONCLUSIONS: Allogeneic
      MSCs maintained immunoprivilege by PGE2-induced secretion of chemokines CCL12 and
      CCL5. Differentiation of MSCs decreased PGE2 levels, and immunoprivilege was
      lost. Maintaining PGE2 levels preserved immunoprivilege after differentiation,
      prevented rejection of implanted MSCs, and restored cardiac function.

PMID- 24030425
TI  - Enhanced survival of transplanted human induced pluripotent stem cell-derived
      cardiomyocytes by the combination of cell sheets with the pedicled omental flap
      technique in a porcine heart.
AB  - BACKGROUND: Transplantation of cardiomyocytes that are derived from human induced
      pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) shows promise in
      generating new functional myocardium in situ, whereas the survival and
      functionality of the transplanted cells are critical in considering this
      therapeutic impact. Cell-sheet method has been used to transplant many functional
      cells; however, potential ischemia might limit cell survival. The omentum, which
      is known to have rich vasculature, is expected to be a source of blood supply. We
      hypothesized that transplantation of hiPS-CM cell sheets combined with an omentum
      flap may deliver a large number of functional hiPS-CMs with enhanced blood
      supply. METHODS AND RESULTS: Retrovirally established human iPS cells were
      treated with Wnt signaling molecules to induce cardiomyogenic differentiation,
      followed by superparamagnetic iron oxide labeling. Cell sheets were created from
      the magnetically labeled hiPS-CMs using temperature-responsive dishes and
      transplanted to porcine hearts with or without the omentum flap (n=8 each). Two
      months after transplantation, the survival of superparamagnetic iron oxide
      labeled hiPS-CMs, assessed by MRI, was significantly greater in mini-pigs with
      the omentum than in those without it; histologically, vascular density in the
      transplanted area was significantly greater in mini-pigs with the omentum than in
      those without it. The transplanted tissues contained abundant cardiac troponin T
      positive cells surrounded by vascular-rich structures. CONCLUSIONS: The omentum
      flap enhanced the survival of hiPS-CMs after transplantation via increased
      angiogenesis, suggesting that this strategy is useful in clinical settings. The
      combination of hiPS-CMs and the omentum flap may be a promising technique for the
      development of tissue-engineered vascular-rich new myocardium in vivo.

PMID- 24030424
TI  - Sustained release of engineered stromal cell-derived factor 1-alpha from
      injectable hydrogels effectively recruits endothelial progenitor cells and
      preserves ventricular function after myocardial infarction.
AB  - BACKGROUND: Exogenously delivered chemokines have enabled neovasculogenic
      myocardial repair in models of ischemic cardiomyopathy; however, these molecules
      have short half-lives in vivo. In this study, we hypothesized that the sustained
      delivery of a synthetic analog of stromal cell-derived factor 1-alpha (engineered
      stromal cell-derived factor analog [ESA]) induces continuous homing of
      endothelial progenitor cells and improves left ventricular function in a rat
      model of myocardial infarction. METHODS AND RESULTS: Our previously designed ESA
      peptide was synthesized by the addition of a fluorophore tag for tracking.
      Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form
      hydrolytically degradable hydrogels through free-radical-initiated crosslinking.
      ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then
      ESA release, along with gel degradation, was monitored for more than 4 weeks in
      vitro. Chemotactic properties of the eluted ESA were assessed at multiple time
      points using rat endothelial progenitor cells in a transwell migration assay.
      Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left
      anterior descending (LAD) coronary artery, and 100 uL of saline, hydrogel alone,
      or hydrogel+25 ug ESA was injected into the borderzone. ESA fluorescence was
      monitored in animals for more than 4 weeks, after which vasculogenic, geometric,
      and functional parameters were assessed to determine the therapeutic benefit of
      each treatment group. ESA release was sustained for 4 weeks in vitro, remained
      active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was
      detected in the rat heart >3 weeks when delivered within the hydrogels and
      significantly improved vascularity, ventricular geometry, ejection fraction,
      cardiac output, and contractility compared with controls. CONCLUSIONS: We have
      developed a hydrogel delivery system that sustains the release of a bioactive
      endothelial progenitor cell chemokine during a 4-week period that preserves
      ventricular function in a rat model of myocardial infarction.

PMID- 24030428
TI  - [Diving risks -- not without consequences for the health].

PMID- 24030426
TI  - Normalization of postinfarct biomechanics using a novel tissue-engineered
      angiogenic construct.
AB  - BACKGROUND: Cell-mediated angiogenic therapy for ischemic heart disease has had
      disappointing results. The lack of clinical translatability may be secondary to
      cell death and systemic dispersion with cell injection. We propose a novel tissue
      engineered therapy, whereby extracellular matrix scaffold seeded with endothelial
      progenitor cells (EPCs) can overcome these limitations using an environment in
      which the cells can thrive, enabling an insult-free myocardial cell delivery to
      normalize myocardial biomechanics. METHODS AND RESULTS: EPCs were isolated from
      the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in
      media or seeded at a density of 5 * 10(6) cells/cm(2) on a collagen/vitronectin
      matrix. Seeded EPCs underwent ex vivo modification with stromal cell-derived
      factor-1alpha (100 ng/mL) to potentiate angiogenic properties and enhance
      paracrine qualities before construct formation. Scanning electron microscopy and
      confocal imaging confirmed EPC-matrix adhesion. In vitro vasculogenic potential
      was assessed by quantifying EPC cell migration and vascular differentiation.
      There was a marked increase in vasculogenesis in vitro as measured by
      angiogenesis assay (8 versus 0 vessels/hpf; P=0.004). The construct was then
      implanted onto ischemic myocardium in a rat model of acute myocardial infarction.
      Confocal microscopy demonstrated a significant migration of EPCs from the
      construct to the myocardium, suggesting a direct angiogenic effect. Myocardial
      biomechanical properties were uniaxially quantified by elastic modulus at 5% to
      20% strain. Myocardial elasticity normalized after implant of our tissue
      engineered construct (239 kPa versus normal=193, P=0.1; versus infarct=304 kPa,
      P=0.01). CONCLUSIONS: We demonstrate restoration and normalization of post
      myocardial infarction ventricular biomechanics after therapy with an angiogenic
      tissue-engineered EPC construct.

PMID- 24030427
TI  - Content analysis of false and misleading claims in television advertising for
      prescription and nonprescription drugs.
AB  - BACKGROUND: False and misleading advertising for drugs can harm consumers and the
      healthcare system, and previous research has demonstrated that physician-targeted
      drug advertisements may be misleading. However, there is a dearth of research
      comparing consumer-targeted drug advertising to evidence to evaluate whether
      misleading or false information is being presented in these ads. OBJECTIVE: To
      compare claims in consumer-targeted television drug advertising to evidence, in
      order to evaluate the frequency of false or misleading television drug
      advertising targeted to consumers. DESIGN: A content analysis of a cross-section
      of television advertisements for prescription and nonprescription drugs aired
      from 2008 through 2010. We analyzed commercial segments containing prescription
      and nonprescription drug advertisements randomly selected from the Vanderbilt
      Television News Archive, a census of national news broadcasts. MAIN MEASURES: For
      each advertisement, the most-emphasized claim in each ad was identified based on
      claim iteration, mode of communication, duration and placement. This claim was
      then compared to evidence by trained coders, and categorized as being objectively
      true, potentially misleading, or false. Potentially misleading claims omitted
      important information, exaggerated information, made lifestyle associations, or
      expressed opinions. False claims were factually false or unsubstantiated. KEY
      RESULTS: Of the most emphasized claims in prescription (n = 84) and
      nonprescription (n = 84) drug advertisements, 33 % were objectively true, 57 %
      were potentially misleading and 10 % were false. In prescription drug ads, there
      were more objectively true claims (43 %) and fewer false claims (2 %) than in
      nonprescription drug ads (23 % objectively true, 7 % false). There were similar
      numbers of potentially misleading claims in prescription (55 %) and
      nonprescription (61 %) drug ads. CONCLUSIONS: Potentially misleading claims are
      prevalent throughout consumer-targeted prescription and nonprescription drug
      advertising on television. These results are in conflict with proponents who
      argue the social value of drug advertising is found in informing consumers about
      drugs.

PMID- 24030429
TI  - [Prescription drug abuse -- athletes ignore pain].

PMID- 24030430
TI  - [Endurance sport -- endurance sport has addiction potential].

PMID- 24030431
TI  - [mental disorders in competitive sports -- the supply needs to be better].

PMID- 24030432
TI  - [Nerve entrapment syndromes in athletes].
AB  - Sports-related injuries most commonly involve the musculoskeletal system.
      However, physicians are less familiar with damage to the peripheral nerves
      attributable to particular sports activities. Nerve entrapment syndromes
      associated with physical activity may affect all nerves for which entrapment
      syndromes are known. Peripheral nerve lesions are serious and may delay or
      preclude the athletes' return to sports, especially in cases with a delayed
      diagnosis. The aim of the paper is to give an overview of chronic sports-related
      nerve lesions. Acute nerve injuries are not the focus of this review. A
      literature search regarding sports-related nerve lesions was conducted. Due to
      the lack of prospective epidemiological studies, case reports were included
      (evidence level 4). Nerve entrapment syndromes specific for particular sports
      activities are described including clinical presentation, diagnostic work-up and
      treatment. Repetitive and vigorous use or overuse makes the athlete vulnerable to
      disorders of the peripheral nerves, additionally sports equipment may cause
      compression of the nerves. The treatment is primarily conservative and includes
      modification of movements and sports equipment, shoe inserts, splinting,
      antiphlogistic drugs and local administration of glucocorticoids. Most often
      cessation of the offending physical activity is necessary. When symptoms are
      refractory to conservative therapy a referral to surgery is indicated. The
      outcome of surgical treatment regarding the return of the athlete to competitive
      sports is not sufficiently investigated in many nerve entrapment -syndromes. This
      article was primarily published in "Akt Neurol 2012; 6: 292-308".

PMID- 24030433
TI  - Mutation spectrum and differential gene expression in cystic and solid vestibular
      schwannoma.
AB  - PURPOSE: We sought to characterize the mutation spectrum of NF2 and the
      differential gene expression in cystic and solid vestibular schwannomas. METHODS:
      We collected tumor tissue and blood samples of 31 cystic vestibular schwannomas
      and 114 solid vestibular schwannomas. Mutation screening of NF2 was performed in
      both tumor and blood DNA samples of all patients. cDNA microarray was used to
      analyze the differential gene expression between 11 cystic vestibular schwannomas
      and 6 solid vestibular schwannomas. Expression levels of top candidate genes were
      verified by quantitative reverse transcription PCR. RESULTS: NF2 mutations were
      identified in 34.5% of sporadic vestibular schwannomas, with all mutations being
      exclusively somatic. No significant difference was found between the mutation
      detection rates of cystic vestibular schwannoma (35.5%) and solid vestibular
      schwannoma (34.2%). cDNA microarray analysis detected a total of 46
      differentially expressed genes between the cystic vestibular schwannoma and solid
      vestibular schwannoma samples. The significantly decreased expression of four top
      candidate genes, C1orf130, CNTF, COL4A3, and COL4A4, was verified by quantitative
      reverse transcription PCR. CONCLUSION: NF2 mutations are not directly involved in
      the cystic formation of vestibular schwannoma. In addition, the differential gene
      expression of cystic vestibular schwannoma reported in our study may provide
      useful insights into the molecular mechanism underlying this process.

PMID- 24030435
TI  - Minimizing liability risks under the ACMG recommendations for reporting
      incidental findings in clinical exome and genome sequencing.
AB  - Recent recommendations by the American College of Medical Genetics and Genomics
      (ACMG) for reporting incidental findings present novel ethical and legal issues.
      This article expresses no views on the ethical aspects of these recommendations
      and focuses strictly on liability risks and how to minimize them. The
      recommendations place labs and clinicians in a new liability environment that
      exposes them to intentional tort lawsuits as well to traditional suits for
      negligence. Intentional tort suits are especially troubling because of their
      potential to inflict ruinous personal financial losses on individual clinicians
      and laboratory personnel. This article surveys this new liability landscape and
      describes analytical approaches for minimizing tort liabilities. To a
      considerable degree, liability risks can be controlled by structuring activities
      in ways that make future lawsuits nonviable before the suits ever arise.
      Proactive liability analysis is an effective tool for minimizing tort liabilities
      in connection with the testing and reporting activities that the ACMG recommends.

PMID- 24030434
TI  - Ethical, legal, and social implications of incorporating genomic information into
      electronic health records.
AB  - The inclusion of genomic data in the electronic health record raises important
      ethical, legal, and social issues. In this article, we highlight these challenges
      and discuss potential solutions. We provide a brief background on the current
      state of electronic health records in the context of genomic medicine, discuss
      the importance of equitable access to genome-enabled electronic health records,
      and consider the potential use of electronic health records for improving genomic
      literacy in patients and providers. We highlight the importance of privacy,
      access, and security, and of determining which genomic information is included in
      the electronic health record. Finally, we discuss the challenges of reporting
      incidental findings, storing and reinterpreting genomic data, and
      nondocumentation and duty to warn family members at potential genetic risk.

PMID- 24030436
TI  - Population-based carrier screening for cystic fibrosis: a systematic review of 23
      years of research.
AB  - Cystic fibrosis is the most common severe autosomal recessive disease, with a
      prevalence of 1 in 2,500-3,500 live births and a carrier frequency of 1 in 25
      among Northern Europeans. Population-based carrier screening for cystic fibrosis
      has been possible since CFTR, the disease-causing gene, was identified in 1989.
      This review provides a systematic evaluation of the literature from the past 23
      years on population-based carrier screening for cystic fibrosis, focusing on the
      following: uptake of testing; how to offer screening; attitudes, opinions, and
      knowledge; factors influencing decision making; and follow-up after screening.
      Recommendations are given for the implementation and evaluation of future carrier
      screening programs.

PMID- 24030438
TI  - The oxygen migration in the apatite-type lanthanum silicate with the cation
      substitution.
AB  - A theoretical model is proposed to determine the effects of Si substitution with
      Al on the oxygen diffusion in apatite-type lanthanum silicates based on density
      functional theory (DFT) calculations for La10(SiO4)4(AlO4)2O2. Substitution
      changes the stable configuration for excess oxygen from the split interstitial to
      a new cluster form with the original cluster. Al doping completely changes the
      migration mechanism from the interstitialcy one, which was proposed for the
      La9.33(SiO4)6O2 starting material, to a mechanism which contains an interstitial
      process. Nevertheless, the migration barrier is calculated to be 0.81 eV, which
      indicates small changes in oxygen conduction and is consistent with the
      observations. The present study indicates that the cation substitution on silicon
      site alone does not promise the improvement of the oxide ion conduction in the
      lanthanum silicate. 

PMID- 24030437
TI  - Stakeholder engagement: a key component of integrating genomic information into
      electronic health records.
AB  - Integrating genomic information into clinical care and the electronic health
      record can facilitate personalized medicine through genetically guided clinical
      decision support. Stakeholder involvement is critical to the success of these
      implementation efforts. Prior work on implementation of clinical information
      systems provides broad guidance to inform effective engagement strategies. We add
      to this evidence-based recommendations that are specific to issues at the
      intersection of genomics and the electronic health record. We describe
      stakeholder engagement strategies employed by the Electronic Medical Records and
      Genomics Network, a national consortium of US research institutions funded by the
      National Human Genome Research Institute to develop, disseminate, and apply
      approaches that combine genomic and electronic health record data. Through select
      examples drawn from sites of the Electronic Medical Records and Genomics Network,
      we illustrate a continuum of engagement strategies to inform genomic integration
      into commercial and homegrown electronic health records across a range of health
      care settings. We frame engagement as activities to consult, involve, and partner
      with key stakeholder groups throughout specific phases of health information
      technology implementation. Our aim is to provide insights into engagement
      strategies to guide genomic integration based on our unique network experiences
      and lessons learned within the broader context of implementation research in
      biomedical informatics. On the basis of our collective experience, we describe
      key stakeholder practices, challenges, and considerations for successful genomic
      integration to support personalized medicine.

PMID- 24030439
TI  - Solid-phase asymmetric synthesis using a polymer-supported chiral Evans'-type
      oxazolidin-2-one.
AB  - This protocol describes the synthesis of (S)-4-(4-hydroxybenzyl)-oxazolidin-2
      one, its attachment to a Merrifield-Cl resin and its use for asymmetric
      synthesis. The chiral auxiliary is prepared in four steps from N-Boc-L-tyrosine
      on a multigram scale in high yield and attached to Merrifield-Cl resin via its
      phenolic group to afford a solid-supported chiral auxiliary for asymmetric
      synthesis that takes ~7 d to prepare. A procedure for its N-acylation is reported
      and a method for carrying out diastereoselective solid-supported Evans' syn-aldol
      reactions is described, with aldol products being cleaved from the polymer by
      either hydrolysis or reduction. The use of the supported auxiliary for two
      sequential 'on-bead' reactions has been demonstrated for the synthesis of a
      chiral cyclopropane aldol and a gamma-lactone in a >95:5 diastereomeric ratio.
      These polymer-supported reactions are carried out in IRORI Kan resin capsules to
      protect the polymer support from mechanical degradation, thus allowing multiple
      on-bead reactions to be performed. 

PMID- 24030440
TI  - Isolation of human monoclonal antibodies from peripheral blood B cells.
AB  - Isolation of monoclonal antibodies is an important technique for understanding
      the specificities and characteristics of antibodies that underlie the humoral
      immune response to a given antigen. Here we describe a technique for isolating
      monoclonal antibodies from human peripheral blood mononuclear cells. The protocol
      includes strategies for the isolation of switch-memory B cells from peripheral
      blood, the culture of B cells, the removal of the supernatant for screening and
      the lysis of B cells in preparation for immunoglobulin heavy-chain and light
      chain amplification and cloning. We have observed that the addition of cytokines
      IL-2, IL-21 and irradiated 3T3-msCD40L feeder cells can successfully stimulate
      switch-memory B cells to produce high concentrations of IgG in the supernatant.
      The supernatant may then be screened by appropriate assays for binding or for
      other functions. This protocol can be completed in 2 weeks. It is adaptable to
      use in other species and enables the efficient isolation of antibodies with a
      desired functional characteristic without prior knowledge of specificity. 

PMID- 24030441
TI  - Targeting mammalian organelles with internalizing phage (iPhage) libraries.
AB  - Techniques that are largely used for protein interaction studies and the
      discovery of intracellular receptors, such as affinity-capture complex
      purification and the yeast two-hybrid system, may produce inaccurate data sets
      owing to protein insolubility, transient or weak protein interactions or
      irrelevant intracellular context. A versatile tool for overcoming these
      limitations, as well as for potentially creating vaccines and engineering
      peptides and antibodies as targeted diagnostic and therapeutic agents, is the
      phage-display technique. We have recently developed a new technology for
      screening internalizing phage (iPhage) vectors and libraries using a
      ligand/receptor-independent mechanism to penetrate eukaryotic cells. iPhage
      particles provide a unique discovery platform for combinatorial intracellular
      targeting of organelle ligands along with their corresponding receptors and for
      fingerprinting functional protein domains in living cells. Here we explain the
      design, cloning, construction and production of iPhage-based vectors and
      libraries, along with basic ligand-receptor identification and validation
      methodologies for organelle receptors. An iPhage library screening can be
      performed in ~8 weeks. 

PMID- 24030442
TI  - Three-dimensional cell culturing by magnetic levitation.
AB  - Recently, biomedical research has moved toward cell culture in three dimensions
      to better recapitulate native cellular environments. This protocol describes one
      method for 3D culture, the magnetic levitation method (MLM), in which cells bind
      with a magnetic nanoparticle assembly overnight to render them magnetic. When
      resuspended in medium, an external magnetic field levitates and concentrates
      cells at the air-liquid interface, where they aggregate to form larger 3D
      cultures. The resulting cultures are dense, can synthesize extracellular matrix
      (ECM) and can be analyzed similarly to the other culture systems using techniques
      such as immunohistochemical analysis (IHC), western blotting and other
      biochemical assays. This protocol details the MLM and other associated techniques
      (cell culture, imaging and IHC) adapted for the MLM. The MLM requires 45 min of
      working time over 2 d to create 3D cultures that can be cultured in the long term
      (>7 d). 

PMID- 24030443
TI  - Autologous meatal skin graft implantation and intratympanic injection of
      Pseudomonas aeruginosa: a new experimental mouse model of acquired middle ear
      cholesteatoma.
AB  - AIM: To create an experimental model for the biomedical research of middle ear
      cholesteatoma. METHODS: Cholesteatoma was induced in the right ears of mice. An
      autologous meatal skin graft was implanted into the middle ear via the tympanic
      membrane followed by an intratympanic injection of Pseudomonas aeruginosa. Six
      weeks after surgery, the formation of acquired cholesteatoma was evaluated by
      macroscopic examination, CT scan, and histological analysis. The expressions of
      TNF-alpha, IL-1beta, and IL-6 were measured with real-time PCR. Auditory-evoked
      brain stem response was used for assessing the changes in hearing levels.
      RESULTS: None of the mice died during the modeling time. By the sixth
      postoperative week, cholesteatoma had successfully formed in 23 out of 25 mice,
      which equals a success rate of 92%. A CT scan revealed that the cholesteatoma was
      eroding the cochlea. Furthermore, histological analysis demonstrated a cystic
      structure covered by stratified squamous epithelium and keratin desquamation in
      the lamellae inside the cystic cavity in the bullae. All mice with experimentally
      induced cholesteatoma showed hearing impairment and an upregulated expression of
      TNF-alpha, IL-1beta, and IL-6. CONCLUSION: The present study successfully
      developed a mouse model of acquired middle ear cholesteatoma, which provides an
      extremely valuable tool for auditory and biomedical research. The modeling
      approach is technically easy and has a high success rate.

PMID- 24030444
TI  - Faecal immunochemical test-based colorectal cancer screening programme SVIT in
      Slovenia: pilot phase.
AB  - Colorectal cancer (CRC) is the second most common cancer in Slovenia. The 5-year
      survival of patients depends on the clinical stage at presentation. More than 70%
      of patients with CRC are diagnosed as being in stage III or IV, with a 5-year
      survival rate of 52.7%. To improve the detection rate of CRC and to detect CRC in
      its early and more curable stage, a national screening programme is needed. In
      the year 2008, we started a pilot phase of the National CRC screening programme.
      We invited 9091 Slovene residents aged 64-68 years from Ljubljana, Kranj, and
      Celje regions, of whom 3807 responded to our invitation (41.9%). Two kits of the
      faecal immune test were sent to 3117 participants who met the inclusion criteria,
      and 2829 (90.7%) tests were returned. The compliance rate in our pilot programme
      was 32.9%. Among the patients who responded positively, 7.5% were positive. Until
      February 2009, 193 colonoscopies had been performed at DC Bled, DC Lipa and AM DC
      Rogaska. Intubation to the caecum was carried out in 99.4% of colonoscopies.
      Histology specimens were taken from 135 patients (70%). The adenoma detection
      rate was 53.8% (59.8% for men and 47.9% for women; P<0.05). We detected 1-17
      adenomas per patient (2.4 on average). Advanced adenomas were detected in 60
      patients (31%; 35.1% of men and 27.1% of women; P<0.05). Invasive carcinoma was
      detected in 15 patients (7.7%; 12.4% of men and 3.1% of women; P<0.05). Ten of
      them (73.3%) were in clinical stage I or II. In the pilot phase of the CRC
      screening programme the majority of CRCs were detected at early clinical stages.
      Invasive cancers were detected in 7.7% of patients. In almost all patients
      adenomas were resected at screening colonoscopy, thus reducing the possibility of
      later development of CRC in those patients. 

PMID- 24030445
TI  - [Oncology and complementary medicine- a contradiction to dialog].

PMID- 24030446
TI  - Extremely low doses of arsenic affect in vitro pollen germination.
AB  - INTRODUCTION: This study deals with the effects of extremely low doses or high
      dilutions of pharmacological compounds on in vitro pollen germination of
      kiwifruit (Actinidia deliciosa). MATERIAL AND METHODS: The biological efficacy of
      As2O3 at the 5th and 45th decimal dilution/succussion level (As 5x and As 45x)
      was tested on pollen previously stressed with As2O3 150 or 200 MUM. The outcome
      variable was the pollen germination rate, as detected blind after 3 h 30 min by
      an Axioplan microscope. RESULTS: A directionally consistent recovery of
      germination percentage was observed in both As 5x and As 45x after stressing with
      As2O3 150 MUM. When pollen was stressed with As2O3 200 MUM only as 45x induced a
      general and significant germination increase. CONCLUSIONS: Our results suggest
      that both treatments might partially remove the inhibitory effect caused by the
      stressor. Similar effects were observed on the same model using weak extremely
      low frequency magnetic fields (ELF-MFs) mediated through water. Although
      preliminary, the findings seem to indicate the in vitro pollen performance as
      adequate to study the effects of physicochemical subthreshold stimuli (extremely
      low doses or high dilutions of pharmacological compounds, weak ELF-MFs), mediated
      through water.

PMID- 24030447
TI  - Dual effects of silymarin on nasopharyngeal carcinoma cells (NPC-TW01).
AB  - BACKGROUND: Silymarin is an active component from the seeds of Silybum marianum
      and is widely used as a hepatic protection agent. Apoptosis induced by silymarin
      has been mentioned in cervical cancer cells. However, silymarin shows dual
      effects on tumor cells: cytostatic action at a low dose and cytotoxic action at
      higher dose. Thus, in the present study, we focused on low-dosing of silymarin in
      nasopharyngeal carcinoma cells, NPC-TW01 (TW01). METHODS: Cell viability assay
      was used to screen the effect of silymarin in TW01 cells. Western blot analysis
      was used to identify the expressions of antioxidant enzymes and anti
      /proapoptotic proteins. Fluorescent dyes are employed to detect the content of
      reactive oxygen species (ROS) and cell apoptosis. RESULTS: Treatment of TW01
      cells with silymarin at a low dose (80 umol/l) resulted in a significant increase
      of antioxidant enzymes. Silymarin increased the expressions of superoxide
      dismutase 1, catalase, and glutathione peroxidase. Consequently, the cell
      apoptosis was reduced markedly. An increase of Bcl-2 expression and a decrease of
      activated caspase-3 or apoptosis-inducing factor (AIF) were observed in TW01
      cells at a low dose (80 umol/l) treatment. CONCLUSION: Silymarin at a low dose
      can induce cytostatic effect on TW01 cells mainly through an increase of
      antioxidant-like action. Thus, silymarin should be applied carefully to patients
      with nasopharyngeal carcinoma.

PMID- 24030448
TI  - [The Flourishing Scale (FS) by Diener et al. is now available in an authorized
      German version (FS-D): application in mind-body medicine].
AB  - BACKGROUND: The Flourishing Scale (FS) of Ed Diener et al. was translated into
      German, tested, and validated for the first time in a German-speaking population,
      as part of an interventional study. METHODS: The FS is a short 8-item
      questionnaire. Items were constructed from various areas that describe subjective
      psychological wellbeing. RESULTS: The German version of FS (FS-D) proved to be a
      stable, reliable, and valid measuring tool for psychological flourishing in
      patients of a mind-body medical outpatient clinic. Basic parameters of the
      original scale could be verified. CONCLUSION: Additionally, relations between
      flourishing, mindfulness, sense of coherence, and health-related quality of life
      (as well as mind-body medicine) are demonstrated.

PMID- 24030449
TI  - Dementia: treating patients and caregivers with complementary and alternative
      medicine--results of a clinical expert conference using the World Cafe method.
AB  - BACKGROUND: In Germany the number of inhabitants with dementia is expected to
      increase from 1.2 million at present to 2.3 million in 2050. Our aim was to
      investigate which treatments complementary and alternative medicine (CAM) experts
      consider to be of therapeutic use in developing treatment strategies and
      hypotheses for further clinical studies. METHODS: In a participatory group
      workshop the 'World Cafe' method was used. As questions we asked: 1) 'Based on
      your clinical experience, which CAM therapies are effective in the treatment of
      patients with dementia? 2) Based on your clinical experience, which CAM therapies
      are effective in the treatment of lay and professional caregivers of patients
      with dementia?, and 3) How should a CAM treatment program look like?' Further
      Delphi rounds were used to reach consensus and summarize the results. RESULTS:
      The 2-day workshop took place in January 2012 in Berlin. A total of 17 experts
      participated. The most important subject in the treatment was the need to
      understand patients' biographies in order to individualize the therapy. Therapy
      itself consists of the therapeutic relationship, nonmedical therapies such as
      sports, massage, music and arts therapy as well as medical treatment such as
      herbal or homeopathic medicines. With regard to caregivers the most important aim
      is to prevent or reduce psychological distress, e.g., by mind-body programs.
      Instead of single treatments, more general elements such as understanding the
      patients' biographies, therapeutic relationships, individualizing, networking,
      and self-care emerged as main results. DISCUSSION: An integrative treatment
      program should connect outpatient and inpatient care as well as all experts. CAM
      training courses should be offered to doctors, nurses, and caregivers. Future
      clinical studies should focus on complex intervention programs integrating these
      key elements.

PMID- 24030450
TI  - The role of complementary medicine in a pediatric day center in Germany.
AB  - BACKGROUND: The role of complementary alternative medicine (CAM) in pediatrics
      has considerably increased in the last years. The knowledge about potential side
      effects and possible interactions with conventional drugs is still limited, and
      often pediatricians do not know whether their patients use CAM. This can be
      critical, as in order to diagnose and treat illnesses properly physicians need to
      know about the full extent of the self-administered therapy of their patients.
      Many studies have been conducted in other countries in order to assess the extent
      of CAM use and the types of substances that are consumed, but in Germany data in
      regard to pediatric interventions are lacking. We therefore developed a
      questionnaire to evaluate the frequency of CAM use among German pediatric
      patients. PATIENTS AND METHODS: 115 parents visiting the pediatric day center in
      Epe between September and November 2011 responded to the questionnaire. The
      survey contains questions concerning the prevalence of CAM use and data about
      socioeconomic factors. RESULTS: A total of 75.7% of all children enrolled in the
      study had already been treated with CAM by their parents, while only 43.6% of the
      parents knew that there can be interactions with CAM and prescribed drugs. In
      only half of the cases (50.6%) the pediatrician knew about the CAM usage of the
      child. CONCLUSION: The frequency of CAM usage among children is higher than
      anticipated. It is essential that pediatricians know about possible interactions
      with conventional medicine, and it lies in their responsibility to include the
      question about CAM usage in their standard protocols.

PMID- 24030451
TI  - Facilitating self-healing in anthroposophic psychotherapy.
AB  - BACKGROUND: The fields of complementary and alternative medicine and
      psychotherapy have many similar characteristics. This study investigates the self
      healing capacity of the patient as one shared characteristic and as an important
      mechanism of change. CASE REPORT: This investigation adopts naturalistic
      qualitative case study methodology to describe the treatment of a patient in his
      late fifties who also had an adjustment disorder with mixed anxiety and depressed
      moods. The data was collected retrospectively from existing data sets and was
      analysed using narrative analysis and the analysis of narratives. The clinical
      work integrated anthroposophic psychotherapy and anthroposophic medicine in order
      to support the patient's self-healing capacities. CONCLUSIONS: The study forms
      the beginning of a research programme and so should ideally be followed up by
      rigorous efficacy and effectiveness studies.

PMID- 24030452
TI  - Ear acupressure for smoking cessation: study protocol for a randomised controlled
      trial.
AB  - BACKGROUND: Smoking is the largest preventable cause of death and disease
      worldwide but smokers often fail to quit due to nicotine withdrawal symptoms.
      Current available pharmaceutical therapies may assist with smoking cessation but
      may have side effects. Ear acupressure (EAP) and ear acupuncture have been used
      for smoking cessation, and some positive results have been reported. The aim of
      the study is to assess the efficacy and safety of EAP in assisting individuals to
      quit smoking and/or support them in the management of nicotine withdrawal
      symptoms. METHODS: This study will be a randomised, single-blind, sham-controlled
      study conducted at RMIT University in Melbourne, Australia. Adult smokers will be
      randomly assigned to receive EAP specifically for smoking cessation or
      nonspecific EAP treatments. After a 2-week run-in, participants will be treated
      once a week for 8 weeks and followed up for 12 weeks. The primary outcome
      measures will be 7 day point-prevalence cessation rate by self-report validated
      by expired carbon monoxide and nicotine withdrawal symptoms measured by the Mood
      and Physical Symptoms Score questionnaire. Secondary outcomes will be self
      reported usage of nicotine replacement therapies, cigarette consumption, body
      weight change and quality of life. The safety end point will be self-reported
      adverse events associated with EAP. Intention-to-treat analysis will be applied.
      DISCUSSION: Findings from this study will determine if this EAP intervention
      alone can be an effective and safe therapy to assist with smoking cessation and
      the management of nicotine withdrawal symptoms.

PMID- 24030453
TI  - Investigating homeopathic verum and placebo globules with UV spectroscopy.

PMID- 24030454
TI  - Uranium mining in Portugal: a review of the environmental legacies of the largest
      mines and environmental and human health impacts.
AB  - The history of uranium mining in Portugal during almost one century has followed
      international demand peaks of both radium and uranium, which in turn were driven
      by medical, military, and civil applications. Nowadays, following price drop in
      the 1980s, mining activities decreased and ceased in 2001. The current challenge
      is to deal with environmental legacies left by old uranium mines, mainly located
      in Viseu and Guarda districts. In 2001, based on several radiological surveys
      carried out, the Portuguese government assumed the remediation costs of abandoned
      mine areas for environmental safety and public health protection. Detailed
      environmental and public health risk assessments were performed under the scope
      of studies both requested by the government and by funded research projects. It
      was found that the existing risks, due to radiological and chemical exposures to
      metals and radionuclide's, were particularly high at the old milling facilities
      and mines where in situ and heap leaching of low-grade ore occurred. The
      different studies, involving both humans and non-human species from different
      trophic levels, demonstrated the existence of effects at different levels of
      biological organization (molecular, cellular, tissues, individuals, and
      populations) and on ecosystem services. To mitigate the risks, the environmental
      rehabilitation works at the Urgeirica mine complex are almost complete, while at
      Cunha Baixa mine, they are presently in progress. These works and environmental
      improvements achieved and expected are described herein. 

PMID- 24030455
TI  - Synthesis of Janus particles via kinetic control of phase separation in emulsion
      droplets.
AB  - A reaction-induced phase separation strategy in emulsion droplets has been
      developed to fabricate non-spherical Janus particles. The final morphology of the
      resulting Janus particles is controlled by a reaction sequence. These Janus
      particles are amphiphilic and show regio-selective adsorption orientation at
      oil/water interfaces. 

PMID- 24030456
TI  - Laser scanning tomography in the EPIC-Norfolk Eye Study: principal components and
      associations.
AB  - PURPOSE: To describe Heidelberg Retina Tomograph (HRT) measures, their principal
      components, and their associations in a British population. METHODS: The European
      Prospective Investigation of Cancer (EPIC)-Norfolk Eye Study is nested within a
      multicenter cohort study. Measurements were taken with the HRT-2 and the software
      subsequently updated to yield HRT-3 parameters. Principal components analysis
      (PCA) was used to identify distinct components of the HRT variables. Generalized
      estimating equation models were used to examine associations of these components
      with age, sex, height, body mass index (BMI), blood pressure, social class,
      education, alcohol intake, smoking status, axial length, IOP, and lens status.
      RESULTS: Complete data were available from 10,859 eyes of 6430 participants with
      a mean age of 68 years. Principal components analysis identified three components
      with an eigenvalue greater than 1, explaining 79.9% of the variance of all the
      HRT measures. These were named cup, retinal nerve fiber layer (RNFL), and rim
      based on the factor loadings they were most correlated with. Older age was
      significantly associated with a greater cup (P = 0.003), smaller RNFL (P <
      0.001), and smaller rim (P < 0.001). Female sex (P = 0.001), higher education (P
      < 0.001), and shorter axial length (P < 0.001) were associated with a greater
      RNFL. Lower BMI and higher IOP were associated with a greater cup (both, P <
      0.001) and a smaller rim (BMI, P = 0.001; IOP, P < 0.001). CONCLUSIONS:
      Heidelberg Retina Tomograph measures in this cohort were largely explained by
      three principal components related to optic disc cup, RNFL, and rim. Associations
      with cup and rim were distinct to associations with RNFL, suggesting different
      underlying determinants.

PMID- 24030457
TI  - Optimal isolation and xeno-free culture conditions for limbal stem cell function.
AB  - PURPOSE: To preserve limbal stem cell (LSC) function in vitro with xenobiotic
      free culture conditions. METHODS: Limbal epithelial cells were isolated from 139
      donors using 15 variations of three dissociation solutions. All culture
      conditions were compared to the baseline condition of murine 3T3-J3 feeders with
      xenobiotic (Xeno) keratinocyte growth medium at 20% O2. Five Xeno and Xeno-free
      media with increasing concentrations of calcium and epidermal growth factor (EGF)
      were evaluated at 5%, 14%, and 20% O2. Human MRC-5, dermal (fetal, neonatal, or
      adult), and limbal stromal fibroblasts were compared. Statistical analysis was
      performed on the number of maximum serial weekly passages, percentage of aborted
      colonies, colony-forming efficiency (CFE), p63alpha(bright) cells, and RT-PCR
      ratio of p63alpha/K12. Immunocytochemistry and RT-PCR for p63alpha, ABCG2, Bmi1,
      C/EBPdelta , K12, and MUC1 were performed to evaluate phenotype. RESULTS:
      Dispase/TrypLE was the isolation method that consistently showed the best yield,
      viability, and CFE. On 3T3-J2 feeders, Xeno-free medium with calcium 0.1 mM and
      EGF 10 ng/mL at 20% O2 supported more passages with equivalent percentage of
      aborted colonies, p63alpha(bright) cells, and p63alpha/K12 RT-PCR ratio compared
      to baseline Xeno-media. With this Xeno-free medium, MRC-5 feeders showed the best
      performance, followed by fetal, neonatal, adult HDF, and limbal fibroblasts. MRC
      5 feeders supported serial passages with sustained high expression of progenitor
      cell markers at levels as robust as the baseline condition without significant
      difference between 20% and 5% O2. CONCLUSIONS: The LSC function can be maintained
      in vitro under appropriate Xeno-free conditions.

PMID- 24030458
TI  - Pigment epithelium-derived factor decreases outflow facility.
AB  - PURPOSE: Pigment epithelium-derived factor (PEDF) regulates blood-retinal barrier
      function. As a constituent of aqueous humor, the role of PEDF in conventional
      outflow function is unknown. The goals of the study were to examine the effects
      of PEDF on barrier function of cultured Schlemm's canal (SC) endothelia and
      outflow facility in mouse eyes in situ. METHODS: To model the inner wall of SC,
      transendothelial electrical resistance (TEER) of human SC and porcine angular
      aqueous plexus (AAP) cells was monitored. To examine an intact conventional
      outflow pathway, enucleated eyes from culled C57BL/6 mice were perfused with PEDF
      using a computer-controlled system. Purified PEDF (0.1 and 1 MUg/mL) was perfused
      at four different pressure steps (4, 8, 15, 20 mm Hg), measuring flow to
      determine outflow facility (slope of flow/pressure relationship). RESULTS:
      Pigment epithelium-derived factor increased TEER of porcine AAP cells in a dose
      dependent fashion (0.3-3 MUg/mL), and 1 MUg/mL recombinant PEDF or conditioned
      media from pigmented retinal pigment epithelial monolayers stabilized TEER of
      human SC monolayers over time (0-48 hours). In perfusion experiments, we observed
      a 43.7% decrease in outflow facility (0.016 vs. 0.029 MUL/min/mm Hg, P = 4.5 * 10
      5) in eyes treated with 1 MUg/mL PEDF compared to vehicle-perfused controls, and
      a 19.9% decrease (0.021 vs. 0.027 MUL/min/mm Hg, P = 0.003) at 100 ng/mL PEDF.
      CONCLUSIONS: Pigment epithelium-derived factor increased barrier function in both
      the in vitro and in situ models of the inner wall of SC. Modification of PEDF
      signaling in SC cells may be therapeutically exploited to increase outflow
      facility in people with ocular hypertension or decrease outflow facility in those
      with hypotony.

PMID- 24030459
TI  - Two-photon imaging of the cornea visualized in the living mouse using vital dyes.
AB  - PURPOSE: To acquire morphological and component information on the overall cornea
      in the living C57BL/6 mouse using fluorescent viability dyes and two-photon (2PH)
      laser microscopy. METHODS: Corneas were scanned using a 2PH laser scanning
      fluorescence microscope after staining with plasma membrane stain and Hoechst
      33342. Representative 2PH images of corneal cells were analyzed and restructured
      using Imaris software. RESULTS: With the plasma membrane- and cell-permeant
      nuclear counter live cell fluorescent probe, the morphology of corneal cells and
      the construction of cornea were observed clearly. The general in vivo morphology
      of the cornea clearly showed three different cellular layers, two interfaces, and
      the nerve fibers. Our study detailed all of the corneal cells with clear cell
      nuclei and cell boundaries at the sections parallel to the surface of the cornea.
      Moreover, cellular stereoscopic images, the relationships of the neighbor cells,
      and the interfaces of different layers were also displayed distinctly with three
      dimensional construction of the 2PH imaging. Our research showed for the first
      time that there are three or four layers of epithelial cells and seven or eight
      layers of keratocytes in mice. CONCLUSIONS: Our study clearly showed the anterior
      limiting lamina and Descemet's membrane in the mouse cornea and showed for the
      first time that there are three or four layers of cells in the epithelium and
      seven or eight layers of keratocytes in the stroma of mice. These results are
      necessary primarily to contribute important insights into the anatomy and
      pathology of the cornea in mice.

PMID- 24030460
TI  - Difference in the properties of retinal nerve fiber layer defect between superior
      and inferior visual field loss in glaucoma.
AB  - PURPOSE: To investigate the patterns of retinal nerve fiber layer (RNFL) defects
      in mean deviation-matched early glaucomatous eyes with either superior or
      inferior visual hemifield loss. METHODS: Seventy-five open-angle glaucoma
      patients with isolated parafoveal scotoma (PFS) within a central 10 degrees  of
      fixation, and 62 patients with isolated peripheral nasal scotoma (PNS) in the
      nasal periphery outside 10 degrees  of fixation were enrolled if the scotoma
      involved only one hemifield. The relationship between the mean threshold
      sensitivity (MS) of each corresponding VF sector and optical coherence tomography
      measured RNFL thickness was assessed by logarithmic regression analysis. The
      angular widths and locations of the RNFL defects were measured from red-free
      fundus photographs. RESULTS: Eyes with superior PFS showed a significant
      relationship between RNFL thickness and corresponding MS at clock-hours 7 and 8
      while eyes with inferior PFS had significant relationship at clock-hours 9, 10,
      and 11. Eyes with superior PNS displayed a significant relationship between RNFL
      thickness and MS at clock-hour 7 while eyes with inferior PNS showed significant
      relationship at clock-hours 11 and 12. Overall, fundus photographs-measured RNFL
      defect associated with inferior hemifield loss (inferior PFS + PNS) was
      significantly wider and closer to the horizontal meridian than those with
      superior hemifield loss (superior PFS + PNS) (P = 0.032 and 0.009, angular width
      and location, respectively). CONCLUSIONS: A superior RNFL defect associated with
      inferior hemifield loss was wider and was located closer to the horizontal
      meridian of the optic disc than an inferior defect with superior field loss,
      particularly in patients with central VF loss.

PMID- 24030462
TI  - Robust and censored modeling and prediction of progression in glaucomatous visual
      fields.
AB  - PURPOSE: Classic regression is based on certain assumptions that conflict with
      visual field (VF) data. We investigate and evaluate different regression models
      and their assumptions in order to determine point-wise VF progression in glaucoma
      and to better predict future field loss for personalised clinical glaucoma
      management. METHODS: Standard automated visual fields of 130 patients with
      primary glaucoma with a minimum of 6 years of follow-up were included.
      Sensitivity estimates at each VF location were regressed on time with classical
      linear and exponential regression models, as well as different variants of these
      models that take into account censoring and allow for robust fits. These models
      were compared for the best fit and for their predictive ability. The prediction
      was evaluated at six measurements (approximately 3 years) ahead using varying
      numbers of measurements. RESULTS: For fitting the data, the classical uncensored
      linear regression model had the lowest root mean square error and 95th percentile
      of the absolute errors. These errors were reduced in all models when increasing
      the number of measurements used for the prediction of future measurements, with
      the classical uncensored linear regression model having the lowest values for
      these errors irrespective of how many measurements were included. CONCLUSIONS:
      All models performed similarly. Despite violation of its assumptions, the
      classical uncensored linear regression model appeared to provide the best fit for
      our data. In addition, this model appeared to perform the best when predicting
      future VFs. However, more advanced regression models exploring any temporal
      spatial relationships of glaucomatous progression are needed to reduce prediction
      errors to clinically meaningful levels.

PMID- 24030461
TI  - Sulforaphane decreases endothelial cell apoptosis in fuchs endothelial corneal
      dystrophy: a novel treatment.
AB  - PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is an oxidative stress
      disorder that leads to age-related and gradual loss of corneal endothelial cells
      resulting in corneal edema and loss of vision. To date, other than surgical
      intervention, there are no treatment options for patients with FECD. We have
      shown that in FECD, there is a deficiency in nuclear factor erythroid 2-related
      factor 2 (Nrf2)-regulated antioxidant defense due to decreased Nrf2 nuclear
      translocation and activation of antioxidant response element (ARE). In this
      study, we used sulforaphane (SFN) and D3T to investigate a strategy of targeting
      Nrf2-ARE in FECD. METHODS: FECD and normal ex vivo corneas and human corneal
      endothelial cell lines were pretreated with SFN or D3T and exposed to oxidative
      stress with tert-Butyl hydroperoxide (tBHP). Apoptosis was detected with TUNEL.
      Cellular localization of Nrf2 and p53 was assessed by immunohistochemistry.
      Effect of SFN was determined by using DCFDA assay, Western blot and real-time
      PCR. RESULTS: After pretreatment with SFN, oxidative stress was induced with
      tBHP. In ex vivo FECD specimens, SFN decreased CEC apoptosis by 55% in unstressed
      group and by 43% in tBHP-treated specimens. SFN enhanced nuclear translocation of
      Nrf2 in FECD specimens and decreased p53 staining under oxidative stress.
      Pretreatment with SFN enhanced cell viability by decreasing intracellular
      reactive oxygen species production. Upregulation of Nrf2 levels led to increased
      synthesis of DJ-1, heme oxygenase 1, and nicotinamide adenine dinucleotide
      quinone oxidoreductase-1. SFN significantly upregulated major ARE-dependent
      antioxidants and ameliorated oxidative stress-induced apoptosis in FECD.
      CONCLUSIONS: Our results suggest that targeting Nrf2-ARE pathway may arrest
      degenerative cell loss seen in FECD.

PMID- 24030463
TI  - Delta-opioid receptors attenuate TNF-alpha-induced MMP-2 secretion from human ONH
      astrocytes.
AB  - PURPOSE: We examined the signaling mechanisms involved in delta-opioid-receptor
      agonist, SNC-121-mediated attenuation of TNF-alpha-induced matrix
      metalloproteinase-2 (MMP-2) secretion from human optic nerve head (ONH)
      astrocytes. METHODS: Human ONH astrocytes were treated with SNC-121 (1 MUmol/L)
      for 15 minutes followed by TNF-alpha (25 ng/mL) treatment for 6 or 24 hours.
      Cells were pretreated with inhibitors of p38 mitogen-activated protein (MAP)
      kinase (SB-203580) or NF-kappaB (Helenalin) prior to TNF-alpha treatment. Changes
      in phosphorylation and expression of p38 MAP kinase, IkappaBalpha, NF-kappaB, and
      MMP-2 were measured by Western blotting. Translocation of NF-kappaB was
      determined by immunocytochemistry. RESULTS: TNF-alpha treatment increased MMP-2
      secretion from ONH astrocytes to 236% +/- 17% and 142% +/- 8% at 6 and 24 hours,
      respectively; while SNC-121 treatment reduced MMP-2 secretion to 149% +/- 11% and
      108% +/- 7% at 6 and 24 hours, respectively. The SNC-121-mediated inhibitory
      response was blocked by the delta-opioid-receptor antagonist naltrindole. TNF
      alpha treatment resulted in a sustained phosphorylation of p38 MAP kinase up to
      24 hours (226% +/- 15% over control levels), which was reduced to 150% +/- 20% by
      SNC-121 treatment. TNF-alpha treatment increased the expression of NF-kappaB to
      179% +/- 21% and 139% +/- 6% at 6 and 24 hours, respectively, which was
      significantly blocked by SNC-121 treatment. Furthermore, TNF-alpha-induced MMP-2
      secretion was blocked by 100% and 78% in the presence of SB-203580 and Helenalin,
      respectively. CONCLUSIONS: Evidence is provided that SNC-121 attenuated TNF-alpha
      induced MMP-2 secretion from ONH astrocytes. Data also supported the idea that
      p38 MAP kinase and NF-kappaB played central roles in TNF-alpha-induced MMP-2
      secretion, and both were negatively regulated by SNC-121.

PMID- 24030464
TI  - Cellular fibronectin expression in human trabecular meshwork and induction by
      transforming growth factor-beta2.
AB  - PURPOSE: Levels of TGF-beta2 are higher in POAG aqueous humor, causing deposition
      of extracellular matrix (ECM) proteins, including fibronectin (FN), in the
      glaucomatous human trabecular meshwork (HTM) that may be responsible for elevated
      IOP. The purpose of this study was to identify the expression of cellular FN
      (cFN) isoforms (EDA and EDB) in HTM cells and tissues, and to determine whether
      TGF-beta2 can induce cFN expression and fibril formation in cultured HTM cells.
      METHODS: Expression of cFN mRNA isoforms and induction by recombinant TGF-beta2
      (5 ng/mL) were determined by quantitative RT-PCR. The TGF-beta2 induction of EDA
      isoform protein expression and FN fibril formation were analyzed using Western
      immunoblots and immunocytochemistry (ICC), respectively. Immunohistochemistry
      (IHC) analysis was used to examine total FN and EDA isoform expression in normal
      (NTM) and glaucomatous (GTM) trabecular meshwork (TM) tissues. RESULTS: Both cFN
      mRNA isoforms were expressed in cultured HTM cells and were induced by TGF-beta2
      after 2, 4, and 7 days (P < 0.05). Similarly, EDA isoform protein and fibril
      formation were increased after 4 and 7 days of TGF-beta2 treatment. Finally, GTM
      tissues had significantly greater EDA isoform protein levels (1.7-fold, P < 0.05)
      compared to NTM tissues. CONCLUSIONS: This study demonstrated that cFN isoforms
      are expressed and induced in HTM cells by TGF-beta2. Also, increased EDA isoform
      protein levels were seen in GTM tissues. Our findings suggest that induction of
      cFN isoform expression in the TM ECM may be a novel pathologic mechanism involved
      in the TM changes associated with glaucoma.

PMID- 24030465
TI  - Functional analysis of serially expanded human iPS cell-derived RPE cultures.
AB  - PURPOSE: To determine the effects of serial expansion on the cellular, molecular,
      and functional properties of human iPS cell (hiPSC)-derived RPE cultures.
      METHODS: Fibroblasts obtained from four individuals were reprogrammed into hiPSCs
      and differentiated to RPE cells using previously described methods. Patches of
      deeply pigmented hiPSC-RPE were dissected, dissociated, and grown in culture
      until they re-formed pigmented monolayers. Subsequent passages were obtained by
      repeated dissociation, expansion, and maturation of RPE into pigmented
      monolayers. Gene and protein expression profiles and morphological and functional
      characteristics of hiPSC-RPE at different passages were compared with each other
      and to human fetal RPE (hfRPE). RESULTS: RPE from all four hiPSC lines could be
      expanded more than 1000-fold when serially passaged as pigmented monolayer
      cultures. Importantly, expansion of hiPSC-RPE monolayers over the first three
      passages (P1-P3) resulted in decreased expression of pluripotency and
      neuroretinal markers and maintenance of characteristic morphological features and
      gene and protein expression profiles. Furthermore, P1 to P3 hiPSC-RPE monolayers
      reliably demonstrated functional tight junctions, G-protein-coupled receptor
      mediated calcium transients, phagocytosis and degradation of photoreceptor outer
      segments, and polarized secretion of biomolecules. In contrast, P4 hiPSC-RPE
      cells failed to form monolayers and possessed altered morphological and
      functional characteristics and gene expression levels. CONCLUSIONS: Highly
      differentiated, pigmented hiPSC-RPE monolayers can undergo limited serial
      expansion while retaining key cytological and functional attributes. However,
      passaging hiPSC-RPE cultures beyond senescence leads to loss of such features.
      Our findings support limited, controlled passaging of patient-specific hiPSC-RPE
      to procure cells needed for in vitro disease modeling, drug screening, and
      cellular transplantation.

PMID- 24030466
TI  - The regional extent of suppression: strabismics versus nonstrabismics.
AB  - PURPOSE: Evidence is accumulating that suppression may be the cause of amblyopia
      rather than a secondary consequence of mismatched retinal images. For example,
      treatment interventions that target suppression may lead to better binocular and
      monocular outcomes. Furthermore, it has recently been demonstrated that the
      measurement of suppression may have prognostic value for patching therapy. For
      these reasons, the measurement of suppression in the clinic needs to be improved
      beyond the methods that are currently available, which provide a binary outcome.
      METHODS: We describe a novel quantitative method for measuring the regional
      extent of suppression that is suitable for clinical use. The method involves a
      dichoptic perceptual matching procedure at multiple visual field locations. We
      compare a group of normal controls (mean age: 28 +/- 5 years); a group with
      strabismic amblyopia (four with microesotropia, five with esotropia, and one with
      exotropia; mean age: 35 +/- 10 years); and a group with nonstrabismic
      anisometropic amblyopia (mean age: 33 +/- 12 years). RESULTS: The extent and
      magnitude of suppression was similar for observers with strabismic and
      nonstrabismic amblyopia. Suppression was strongest within the central field and
      extended throughout the 20 degrees  field that we measured. CONCLUSIONS:
      Suppression extends throughout the central visual field in both strabismic and
      anisometropic forms of amblyopia. The strongest suppression occurs within the
      region of the visual field corresponding to the fovea of the fixing eye.

PMID- 24030468
TI  - Age-dependent alterations in reward-seeking behavior after brief nicotine
      exposure.
AB  - RATIONALE: Adolescence is a developmental period that coincides with the onset of
      tobacco use. Teen smokers are also more likely to abuse other drugs compared to
      nonsmokers. Previous studies with rats have shown that low-dose nicotine
      pretreatment enhances initial acquisition of cocaine self-administration when
      given during early adolescence, but not at later ages. The aim of the present
      study was to determine whether these nicotine pretreatment effects extend to
      extinction and reinstatement of reward-seeking behavior. METHODS: Adolescent
      [postnatal day (P)28] and adult rats (P86) were pretreated for 4 days with
      nicotine (60 MUg/kg, i.v.) or saline. Following pretreatment, rats were allowed
      to nose poke for cocaine (500 MUg/kg/infusion) or sucrose pellets for at least 12
      days or until meeting acquisition criterion. Responding was then extinguished for
      at least 7 days or until extinction criterion was met. The following day, the
      rats were reinstated with either a priming injection of cocaine (10 mg/kg, i.p.)
      or sucrose pellets. RESULTS: Nicotine markedly enhanced extinction of cocaine
      self-administration in adolescent rats, but not adults. Pretreatment also
      enhanced the acquisition of cocaine self-administration in adolescents, while
      reducing discrimination for the reinforced hole in adults. There were no
      pretreatment or age effects on cocaine-induced reinstatement. In contrast,
      nicotine induced only minor enhancement of sucrose-taking behavior in
      adolescents, with no significant impact on extinction or reinstatement at either
      age. CONCLUSIONS: Nicotine pretreatment affects reward-related behavior in both
      an age- and reward-dependent manner. These findings show that brief nicotine
      exposure during early adolescence enhances drug-related learning.

PMID- 24030467
TI  - Rat strain differences in brain structure and neurochemistry in response to binge
      alcohol.
AB  - RATIONALE: Ventricular enlargement is a robust phenotype of the chronically
      dependent alcoholic human brain, yet the mechanism of ventriculomegaly is
      unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg
      intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of
      250 mg/dL) demonstrate profound but reversible ventricular enlargement and
      changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline
      containing compounds (Cho)). OBJECTIVES: Here, alcohol-preferring (P) and alcohol
      nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats
      for differential alcohol drinking behavior were compared with Wistar rats to
      determine whether genetic divergence and consequent morphological and
      neurochemical variation affect the brain's response to binge EtOH treatment.
      METHODS: The three rat lines were dosed equivalently and approached similar BALs.
      Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH
      on brain. RESULTS: As observed in Wistar rats, P and NP rats showed decreases in
      NAA. Neither P nor NP rats, however, responded to EtOH intoxication with
      ventricular expansion or increases in Cho levels as previously noted in Wistar
      rats. Increases in ventricular volume correlated with increases in Cho in Wistar
      rats. CONCLUSIONS: The latter finding suggests that ventricular volume expansion
      is related to adaptive changes in brain cell membranes in response to binge EtOH.
      That P and NP rats responded differently to EtOH argues for intrinsic differences
      in their brain cell membrane composition. Further, differential metabolite
      responses to EtOH administration by rat strain implicate selective genetic
      variation as underlying heterogeneous effects of chronic alcoholism in the human
      condition.

PMID- 24030469
TI  - Interactions between age and moderate alcohol effects on simulated driving
      performance.
AB  - RATIONALE: There is a substantial body of literature documenting the deleterious
      effects of both alcohol consumption and age on driving performance. There is,
      however, limited work examining the interaction of age and acute alcohol
      consumption. OBJECTIVES: The current study was conducted to determine if moderate
      alcohol doses differentially affect the driving performance of older and younger
      adults. METHODS: Healthy older (55-70) and younger (25-35) adults were tested
      during a baseline session and again following consumption of one of three
      beverages [0.0 % (placebo), 0.04 % or 0.065 % target breath alcohol
      concentration]. Measures of driving precision and average speed were recorded.
      RESULTS: Older adults performed more poorly on precision driving measures and
      drove more slowly than younger adults at baseline. After controlling for baseline
      performance, interactions between alcohol and age were observed following
      beverage consumption on two measures of driving precision with older adults
      exhibiting greater impairment as a result of alcohol consumption. CONCLUSIONS:
      These data provide evidence that older adults may be more susceptible to the
      effects of alcohol on certain measures of driving performance. An investigation
      of mechanisms accounting for alcohol's effects on driving in older and younger
      adults is required. Further evaluation using more complex driving environments is
      needed to assess the real-world implication of this interaction.

PMID- 24030471
TI  - The conditional-recency dissociation is confounded with nominal recency: should
      unitary models of memory still be devaluated?
AB  - The conditional-recency dissociation between immediate and delayed free recall
      FR; Farrell (Journal of Experimental Psychology: Learning, Memory, and Cognition,
      36, 324-347, 2010) has critical implications regarding the prolonged debate
      between unitary and dual-store models of memory. In immediate FR, when the
      availability of items is controlled for, the recency of the final list item
      increases across the first few output positions. No such increase is found in
      delayed FR, with a trend in the opposite direction. This dissociation challenges
      temporal context TCM; Howard & Kahana (Journal of Mathematical Psychology, 46,
      269-299, 2002) and distinctiveness SIMPLE; Brown, Neath, & Chater (Psychological
      Review, 114, 539-576, 2007) unitary models of memory and suggests the involvement
      of a short-term buffer in immediate FR. We show that this dissociation is
      confounded with the different magnitudes of nominal recency (i.e., the prevalence
      of the final list item) found in immediate as compared to delayed FR. By
      reshuffling output orders and comparing the empirical results to those of a null
      hypothesis of no output-order effect, we controlled for the greater prevalence of
      the final list item that has been observed in immediate FR. Under this control,
      we found no evidence for a dissociation in the tendency to recall the final list
      item across output positions. This finding suggests that the conditional-recency
      dissociation imposes no new constraint on unitary models of memory. More
      generally, we demonstrate how biases that influence measures of output-order
      tendencies (e.g., conditional recency) can be controlled for, thus yielding
      "purer" measures of these variables.

PMID- 24030470
TI  - Feeding condition and the relative contribution of different dopamine receptor
      subtypes to the discriminative stimulus effects of cocaine in rats.
AB  - RATIONALE: The contribution of dopamine receptor subtypes in mediating the
      discriminative stimulus effects of cocaine is not fully established. Many drug
      discrimination studies use food to maintain responding, necessitating food
      restriction, which can alter drug effects. OBJECTIVE: This study established
      stimulus control with cocaine (10 mg/kg) in free-feeding and food-restricted rats
      responding under a schedule of stimulus shock termination (SST) and in food
      restricted rats responding under a schedule of food presentation to examine
      whether feeding condition or the reinforcer used to maintain responding impacts
      the effects of cocaine. METHOD: Dopamine receptor agonists and antagonists were
      examined for their ability to mimic or attenuate, respectively, the effects of
      cocaine. RESULTS: Apomorphine, quinpirole, and lisuride occasioned >90 %
      responding on the cocaine-associated lever in free-feeding rats responding under
      a schedule of SST; apomorphine, but not quinpirole or lisuride, occasioned >90 %
      responding on the cocaine lever in food-restricted rats responding under a
      schedule of SST. In food-restricted rats responding for food these drugs
      occasioned little cocaine lever responding and were comparatively more potent in
      decreasing responding. In free-feeding rats, the effects of cocaine were
      attenuated by the D2/D3 receptor antagonist raclopride and the D3 receptor
      selective antagonist PG01037. In food-restricted rats, raclopride and the D2
      receptor-selective antagonist L-741,626 attenuated the effects of cocaine.
      Raclopride antagonized quinpirole in all groups while PG01037 antagonized
      quinpirole only in free-feeding rats. CONCLUSION: These results demonstrate
      significant differences in the discriminative stimulus of cocaine that are due to
      feeding conditions and not to the use of different reinforcers across procedures.

PMID- 24030472
TI  - Cognitive processing and motor execution in the lexical decision task: a
      developmental study.
AB  - We investigated lexical decision making in children and adults by analyzing
      spatiotemporal characteristics of responses involving a hand movement. Children's
      and adults' movement trajectories were assessed in three tasks: a lexical
      decision task (LDT), a pointing task that involved minimal cognitive processing,
      and a symbol task requiring a simple binary decision. Cognitive interference on
      motor performance was quantified by analyzing movement characteristics in the LDT
      and symbol task relative to the pointing task. Across age groups, movements in
      the LDT were less smooth, slower, and more strongly curved to the opposite
      response option, and these interference effects decreased steadily with age.
      Older children showed stronger interference effects than did adults, even though
      their reaction times were similar to adults' performance. No comparable effects
      were found in the symbol task, indicating that task characteristics such as
      response mapping and decision selection alone are not able to explain the
      developmental differences observed in the LDT. Our results indicate substantial
      overlap between cognitive processing and motor execution in the LDT in children
      that is not captured by computational models of visual word recognition and
      cognitive development.

PMID- 24030474
TI  - Synthesis, characterization and selective de-esterification of diorganotinbis(O
      methylphosphite)s.
AB  - A one-pot reaction between di-n-butyl/diethyl/dimethyltin dichloride and
      dimethylphosphite (MeO)2P(O)H in a solvent free medium (120  degrees C, 18 h)
      proceeds smoothly to yield the corresponding diorganotinbis(O-methylphosphite)s,
      [R2Sn(OP(O)(OMe)H)2]n [R = n-Bu (1), Et (2), Me (3)]. The identity of 1-3 has
      been established by IR, multinuclear ((1)H, (13)C, (31)P, (119)Sn) NMR, powder X
      ray diffraction (PXRD) and X-ray crystallography. The coordination framework in
      each case adopts a one-dimensional structural motif comprising an infinite array
      of eight-membered [Sn-O-P-O]2 cyclic rings, with the phosphite ligands acting in
      a bridging bidentate mode. The structures are extended to two- (for 1) and three
      dimensional (for 2, 3) assemblies by virtue of C-H...O hydrogen bonding
      interactions. The stability and bulk properties of 1-3 have been investigated
      upon exposure to humid laboratory conditions using (1)H NMR, PXRD and SEM
      studies. The results conform to a unique chemical modification of 1-3 involving
      selective de-esterification of P-OMe bonds and the formation of corresponding
      diorganotinbis(phosphite)s, [R2Sn(OP(O)(OH)H)2]n (1a-3a), as insoluble solids.
      The results obtained from impedance studies (sigma = 10(-4)-10(-6) S cm(-1); E(a)
      = 0.33-0.42 eV) reveal potential application of 1a-3a as proton conducting
      materials.

PMID- 24030473
TI  - Identification of novel markers for mouse CD4(+) T follicular helper cells.
AB  - CD4(+) T follicular helper (TFH) cells are central for generation of long-term B
      cell immunity. A defining phenotypic attribute of TFH cells is the expression of
      the chemokine R CXCR5, and TFH cells are typically identified by co-expression of
      CXCR5 together with other markers such as PD-1, ICOS, and Bcl-6. Herein, we
      report high-level expression of the nutrient transporter folate R 4 (FR4) on TFH
      cells in acute viral infection. Distinct from the expression profile of
      conventional TFH markers, FR4 was highly expressed by naive CD4(+) T cells, was
      downregulated after activation and subsequently re-expressed on TFH cells.
      Furthermore, FR4 expression was maintained, albeit at lower levels, on memory TFH
      cells. Comparative gene expression profiling of FR4(hi) versus FR4(lo) Ag
      specific CD4(+) effector T cells revealed a molecular signature consistent with
      TFH and TH1 subsets, respectively. Interestingly, genes involved in the purine
      metabolic pathway, including the ecto-enzyme CD73, were enriched in TFH cells
      compared with TH1 cells, and phenotypic analysis confirmed expression of CD73 on
      TFH cells. As there is now considerable interest in developing vaccines that
      would induce optimal TFH cell responses, the identification of two novel cell
      surface markers should be useful in characterization and identification of TFH
      cells following vaccination and infection. 

PMID- 24030476
TI  - Quality of life and parental adjustment in pediatric pulmonary hypertension.
AB  - BACKGROUND: This study examines the impact of pulmonary hypertension (PH) on the
      quality of life (QoL) of affected youth, as well as the relationships among PH
      disease severity, parental adjustment variables, and family relational
      functioning. METHODS: Subjects were 47 eligible parents of children with PH aged
      2 to 18 years who were evaluated at Boston Children's Hospital. Measures of
      patient QoL and of parental stress, coping, and adjustment were administered to
      the caregivers. Clinicians rated illness severity and family relational
      functioning. RESULTS: Youth with PH scored significantly lower than healthy norms
      on a measure of parent-reported QoL (total, psychosocial, and physical QoL, each
      P < .0001). The parents reported encountering stressful events more frequently
      than published norms of parents of children with cancer (P < .0001). Thirty-four
      percent of parents of children with PH met criteria for presumed psychiatric
      diagnosis, and they reported using psychologic coping strategies significantly
      more often than a normative sample. A summary parental stress measure correlated
      inversely with child QoL, an effect that held true even after controlling for
      disease severity (P = .03). CONCLUSIONS: PH takes a major toll on children and
      their families. Decreased QoL among youth with PH was significantly associated
      with high levels of parental stress, over and above the effect of illness
      severity. These findings suggest that interventions to better support the
      caretakers of affected children and adolescents should accompany medical
      treatment advances so as to improve QoL for patients facing pediatric PH.

PMID- 24030477
TI  - Comparison of expert and novice performance of a simulated transesophageal
      echocardiography examination.
AB  - INTRODUCTION: Training in transesophageal echocardiography (TEE) requires a
      significant commitment of time and resources on behalf of the trainees and the
      instructors. Training opportunities may be limited in the busy clinical
      environment. Medical simulation has emerged as a complementary means by which to
      develop clinical skills. Transesophageal echocardiography simulators have been
      commercially available for several years, yet their ability to distinguish
      experts from novices has not been demonstrated. We used a standardized assessment
      tool to distinguish experts from novices using a commercially available TEE
      simulator. METHODS: Anesthesiologists certified in advanced perioperative TEE and
      anesthesiology resident physicians were recruited into the expert and novice
      cohorts, respectively. The cohorts were recruited from 2 academic medical
      centers. The novice cohort received a structured introduction to the basic TEE
      examination. Both cohorts then proceeded to perform a basic TEE examination
      involving normal cardiac anatomy, which was evaluated by blinded raters using a
      standardized assessment tool. RESULTS: The expert cohort consistently
      demonstrated the ability to obtain standard TEE imaging views in less time and
      more accurately than the novice cohort during the course of a simulated TEE
      examination. CONCLUSIONS: A simulated transesophageal examination of normal
      cardiac anatomy in concert with a standardized assessment tool permits ample
      discrimination between expert and novice echocardiographers as defined for this
      investigation. Future research will examine in detail the role echocardiography
      simulators should play during echocardiography training including assessment of
      training level.

PMID- 24030478
TI  - Mechanism and microkinetics of the Fischer-Tropsch reaction.
AB  - The increasing availability of quantum-chemical data on surface reaction
      intermediates invites one to revisit unresolved mechanistic issues in
      heterogeneous catalysis. One such issue of particular current interest is the
      molecular basis of the Fischer-Tropsch reaction. Here we review current molecular
      understanding of this reaction that converts synthesis gas into longer
      hydrocarbons where we especially elucidate recent progress due to the
      contributions of computational catalysis. This perspective highlights the
      theoretical approach to heterogeneous catalysis that aims for kinetic prediction
      from quantum-chemical first principle data. Discussion of the Fischer-Tropsch
      reaction from this point of view is interesting because of the several
      mechanistic options available for this reaction. There are many proposals on the
      nature of the monomeric single C atom containing intermediate that is inserted
      into the growing hydrocarbon chain as well as on the nature of the growing
      hydrocarbon chain itself. Two dominant conflicting mechanistic proposals of the
      Fischer-Tropsch reaction that will be especially compared are the carbide
      mechanism and the CO insertion mechanism, which involve cleavage of the C-O bond
      of CO before incorporation of a CHx species into the growing hydrocarbon chain
      (the carbide mechanism) or after incorporation into the growing hydrocarbon chain
      (the CO insertion mechanism). The choice of a particular mechanism has important
      kinetic consequences. Since it is based on molecular information it also affects
      the structure sensitivity of this particular reaction and hence influences the
      choice of catalyst composition. We will show how quantum-chemical information on
      the relative stability of relevant reaction intermediates and estimates of the
      rate constants of corresponding elementary surface reactions provides a firm
      foundation to the kinetic analysis of such reactions and allows one to
      discriminate between the different mechanistic options. The paper will be
      concluded with a short perspective section dealing with the needs for future
      research. Many of the current key questions on the physical chemistry as well as
      computational study of heterogeneous catalysis relate to particular topics for
      further research on the fundamental aspects of Fischer-Tropsch catalysis. 

PMID- 24030475
TI  - The International Society for Bipolar Disorders (ISBD) task force report on
      antidepressant use in bipolar disorders.
AB  - OBJECTIVE: The risk-benefit profile of antidepressant medications in bipolar
      disorder is controversial. When conclusive evidence is lacking, expert consensus
      can guide treatment decisions. The International Society for Bipolar Disorders
      (ISBD) convened a task force to seek consensus recommendations on the use of
      antidepressants in bipolar disorders. METHOD: An expert task force iteratively
      developed consensus through serial consensus-based revisions using the Delphi
      method. Initial survey items were based on systematic review of the literature.
      Subsequent surveys included new or reworded items and items that needed to be
      rerated. This process resulted in the final ISBD Task Force clinical
      recommendations on antidepressant use in bipolar disorder. RESULTS: There is
      striking incongruity between the wide use of and the weak evidence base for the
      efficacy and safety of antidepressant drugs in bipolar disorder. Few well
      designed, long-term trials of prophylactic benefits have been conducted, and
      there is insufficient evidence for treatment benefits with antidepressants
      combined with mood stabilizers. A major concern is the risk for mood switch to
      hypomania, mania, and mixed states. Integrating the evidence and the experience
      of the task force members, a consensus was reached on 12 statements on the use of
      antidepressants in bipolar disorder. CONCLUSIONS: Because of limited data, the
      task force could not make broad statements endorsing antidepressant use but
      acknowledged that individual bipolar patients may benefit from antidepressants.
      Regarding safety, serotonin reuptake inhibitors and bupropion may have lower
      rates of manic switch than tricyclic and tetracyclic antidepressants and
      norepinephrine-serotonin reuptake inhibitors. The frequency and severity of
      antidepressant-associated mood elevations appear to be greater in bipolar I than
      bipolar II disorder. Hence, in bipolar I patients antidepressants should be
      prescribed only as an adjunct to mood-stabilizing medications.

PMID- 24030479
TI  - SCOPE: a scorecard for osteoporosis in Europe.
AB  - SUMMARY: The scorecard summarises key indicators of the burden of osteoporosis
      and its management in each of the member states of the European Union. The
      resulting scorecard elements were then assembled on a single sheet to provide a
      unique overview of osteoporosis in Europe. INTRODUCTION: The scorecard for
      osteoporosis in Europe (SCOPE) is an independent project that seeks to raise
      awareness of osteoporosis care in Europe. The aim of this project was to develop
      a scorecard and background documents to draw attention to gaps and inequalities
      in the provision of primary and secondary prevention of fractures due to
      osteoporosis. METHODS: The SCOPE panel reviewed the information available on
      osteoporosis and the resulting fractures for each of the 27 countries of the
      European Union (EU27). The information researched covered four domains:
      background information (e.g. the burden of osteoporosis and fractures), policy
      framework, service provision and service uptake e.g. the proportion of men and
      women at high risk that do not receive treatment (the treatment gap). RESULTS:
      There was a marked difference in fracture risk among the EU27. Of concern was the
      marked heterogeneity in the policy framework, service provision and service
      uptake for osteoporotic fracture that bore little relation to the fracture
      burden. For example, despite the wide availability of treatments to prevent
      fractures, in the majority of the EU27, only a minority of patients at high risk
      receive treatment for osteoporosis even after their first fracture. The elements
      of each domain in each country were scored and coded using a traffic light system
      (red, orange, green) and used to synthesise a scorecard. The resulting scorecard
      elements were then assembled on a single sheet to provide a unique overview of
      osteoporosis in Europe. CONCLUSIONS: The scorecard will enable healthcare
      professionals and policy makers to assess their country's general approach to the
      disease and provide indicators to inform future provision of healthcare.

PMID- 24030480
TI  - Energy drinks and alcohol: research supported by industry may be downplaying
      harms.

PMID- 24030481
TI  - Antimicrobial ergosteroids and pyrrole derivatives from halotolerant Aspergillus
      flocculosus PT05-1 cultured in a hypersaline medium.
AB  - In order to obtain more structurally novel and bioactive lead compounds for
      subsequent drug discovery, we have shifted the focus of our study from
      traditional microbial resources to 'extremophiles'. In this study, a halotolerant
      fungus Aspergillus flocculosus PT05-1 was isolated from the sediment of Putian
      saltern of Fujian Province of China in a hypersaline medium. Two new compounds,
      (22R,23S)-epoxy-3beta,11alpha,14beta,16beta-tetrahydroxyergosta-5,7-dien-12-one
      (1) and 6-(1H-pyrrol-2-yl)hexa-1,3,5-trienyl-4-methoxy-2H-pyran-2-one (5)
      (existed as a pair of epimers with the configuration of 1E,3Z,5E and 1E,3E,5E
      separately), along with nine known compounds were isolated and identified from
      the fermentation broth of A. flocculosus PT05-1 grown at a 10 % saline medium.
      New ergosteroid 1 together with 7-nor-ergosterolide (2) and 3beta-hydroxyergosta
      8,24(28)-dien-7-one (3) showed cytotoxicity against HL-60 and BEL-7402 cells with
      IC50 values of 12-18 MUM, and antimicrobial activity against Enterobacter
      aerogenes, Pseudomonas aeruginosa, and Candida albicans with MIC values of 1.6-15
      MUM, respectively. New compound 5 exhibited antibacterial effect on E. aerogenes
      with MIC value of 3.7 MUM. This study also showed great prospects in developing
      medicinal resources from extremophiles. 

PMID- 24030482
TI  - Stress fermentation strategies for the production of hyperthermostable superoxide
      dismutase from Thermus thermophilus HB27: effects of ions.
AB  - In this study, we explored how ammonium and metal ion stresses affected the
      production of recombinant hyperthermostable manganese superoxide dismutase (Mn
      SOD). To improve Mn-SOD production, fed-batch culture in shake flasks and
      bioreactor fermentation were undertaken to examine the effects of [Formula: see
      text] and Mn(2+) feeding. Under the optimized feeding time and concentrations of
      [Formula: see text] and Mn(2+), the maximal SOD activity obtained from bioreactor
      fermentation reached some 480 U/ml, over 4 times higher than that in batch
      cultivation (113 U/ml), indicating a major enhancement of the concentration of Mn
      SOD in the scale-up of hyperthermostable Mn-SOD production. In contrast, when the
      fed-batch culture with appropriate [Formula: see text] and Mn(2+) feeding was
      carried out in the same 5-L stirred tank bioreactor, a maximal SOD concentration
      of some 450 U/ml was obtained, again indicating substantial increase in SOD
      activity as a result of [Formula: see text] and Mn(2+) feeding. The isoelectric
      point (pI) of the sample was found to be 6.2. It was highly stable at 90  degrees
      C and circular dichroism measurements indicated a high alpha-helical content of
      70 % as well, consistent with known SOD properties. This study indicates that
      [Formula: see text] and Mn(2+) play important roles in Mn-SOD expression. Stress
      fermentation strategies established in this study are useful for large-scale
      efficient production of hyperthermostable Mn-SOD and may also be valuable for the
      scale-up of other extremozymes. 

PMID- 24030483
TI  - Disproportionation of elemental sulfur by haloalkaliphilic bacteria from soda
      lakes.
AB  - Microbial disproportionation of elemental sulfur to sulfide and sulfate is a
      poorly characterized part of the anoxic sulfur cycle. So far, only a few
      bacterial strains have been described that can couple this reaction to cell
      growth. Continuous removal of the produced sulfide, for instance by oxidation
      and/or precipitation with metal ions such as iron, is essential to keep the
      reaction exergonic. Hitherto, the process has exclusively been reported for
      neutrophilic anaerobic bacteria. Here, we report for the first time
      disproportionation of elemental sulfur by three pure cultures of haloalkaliphilic
      bacteria isolated from soda lakes: the Deltaproteobacteria Desulfurivibrio
      alkaliphilus and Desulfurivibrio sp. AMeS2, and a member of the Clostridia,
      Dethiobacter alkaliphilus. All cultures grew in saline media at pH 10 by sulfur
      disproportionation in the absence of metals as sulfide scavengers. Our data
      indicate that polysulfides are the dominant sulfur species under highly alkaline
      conditions and that they might be disproportionated. Furthermore, we report the
      first organism (Dt. alkaliphilus) from the class Clostridia that is able to grow
      by sulfur disproportionation. 

PMID- 24030484
TI  - Isolation and characterization of a metagenome-derived thermoalkaliphilic
      esterase with high stability over a broad pH range.
AB  - A novel alkaliphilic esterase (EstJ) was identified from a soil metagenome of
      Jeju Island, Korea, using a 96-well plate-based functional assay for
      determination of pH dependence of activity. The amino acid sequence of EstJ
      showed low similarity (32-45 %) to putative alpha/beta hydrolases derived from
      whole-genome sequencing studies. EstJ, although not belonging to any of the known
      families of bacterial lipolytic enzymes, however, it showed closest sequence
      identity to the family IV enzymes that are related to the mammalian hormone
      sensitive lipases. The highly conserved motifs of family IV enzymes were found in
      EstJ, but the corresponding sequences of each motif in EstJ were unique; most
      particularly the -(F/Y)(F/Y/L)HGGG- motif was represented by -WMVSGG-. The
      purified EstJ was highly active from pH 8.5 to 10.5. More than 90 % of maximum
      activity was also retained over a wide pH range of 5.5-0.5 after prolonged
      incubation. EstJ was also moderately thermophilic with an optimum temperature of
      55  degrees C. Therefore, EstJ is the first metagenome-derived bacterial family
      IV esterase possessing both highly alkaliphilic and moderately thermophilic
      properties. 

PMID- 24030485
TI  - Delayed hemothorax superimposed on extrapleural hematoma after blunt chest
      injury: a case report.
AB  - We report a case showing delayed hemothorax superimposed on extrapleural hematoma
      after blunt chest injury. The patient was a 56-year-old man with a medical
      history of alcoholic hepatopathy who presented with a chief complaint of dyspnea
      on exertion. One month prior to presentation, he had sustained a fall that had
      resulted in left simple rib fracture. A chest radiograph taken at the time of
      injury showed notable reduction in the permeability of the left lung field along
      with high pulmonary collapse as well as rightward deviation of the shadow of the
      inferior mediastinum. Chest CT images showed a region of low absorption in the
      thoracic cavity with septi. Thoracic drainage was performed (1,300 mL total) and
      hemothorax was diagnosed. Thoracoscopic examination was then performed. When the
      inside of the thorax was observed, what had been presumed to be the septi of a
      multilocular fluid collection was found to be actually the parietal pleura, and a
      hematoma was confirmed inside the extrapleural cavity. The hematoma inside the
      extrapleural cavity was managed with lavage and drainage, and drainage tubes were
      placed inside both the thoracic cavity and extrapleural cavity at the end of the
      procedure. The patient's postoperative course was uneventful, and he was
      discharged on postoperative day 4. 

PMID- 24030486
TI  - Pleomorphic lobular carcinoma with lipid-producing activity: a report of 2 cases.
AB  - This case report presented 2 cases of pleomorphic lobular carcinoma (PLC) of the
      breast with lipid-producing activity, a type of cancer that has not been
      previously reported in the literature. The patients were 2 Japanese women aged 67
      and 57 years, respectively, who presented with the chief complaint of an indolent
      tumor mass of the left breast. Both patients underwent breast conserving surgery
      and axillary sentinel node biopsy. Pathological analysis of breast tissue
      specimens revealed carcinoma cells, most of which contained abundant granular or
      foamy cytoplasm, enlarged round nuclei with prominent nucleoli, and
      intracytoplasmic lumens (ICLs). Digested periodic acid-Schiff (PAS) staining
      revealed diastase-resistant PAS staining in the ICLs, while Sudan III and oil 
      red -O staining revealed lipid granules in the cytoplasm. Immunohistochemically,
      the carcinoma cells from both cases tested negative for E-cadherin but positive
      for gross cystic disease fluid protein-15, cytokeratin, and mucin 1.
      Consideration of these findings led to a diagnosis of PLC with lipid-producing
      activity. 

PMID- 24030487
TI  - Comparison of ionic, monomer, high osmolar contrast media with non-ionic, dimer,
      iso-osmolar contrast media in ERCP.
AB  - OBJECTIVE: Pancreatitis is the most common and serious complication of endoscopic
      retrograde cholangiopancreatography (ERCP). Several studies have compared
      contrast media (CM) with different osmolalities, but the results are conflicting.
      We conducted this study to clarify the difference between 2 CM used in ERCP.
      METHODS: Five hundred and seventy-six patients were examined by using ERCP in our
      hospital during 2010. Out of these, 56 patients were enrolled in this study. We
      investigated the incidence of post ERCP pancreatitis (PEP) and hyperamylasemia.
      Serum amylase levels were compared in the 2 groups. RESULTS: Twenty-seven
      patients were treated with iodixanol and 29 with diatrizoate meglumine Na. The
      rate of PEP in the diatrizoate meglumine Na group and iodixanol group was 0%
      (0/29) and 7.4% (2/27), respectively (P = 0.228). The rate of hyperamylasemia was
      10.3% (3/29) and 14.8% (4/27), respectively (P = 0.70). There were no significant
      differences between two groups for amylase levels pre-procedure (P = 0.082), 3 h
      post procedure (P = 0.744), or next morning (P = 0.265). CONCLUSIONS: There were
      no significant differences in the rates of PEP or hyperamylasemia between CMs in
      ERCP. We believe it is unnecessary to use the more expensive low osmolality CM in
      ERCP to prevent PEP.

PMID- 24030488
TI  - beta7 integrins are required to give rise to intestinal mononuclear phagocytes
      with tolerogenic potential.
AB  - BACKGROUND AND OBJECTIVE: While pro-inflammatory monocyte trafficking to the
      intestine has been partially characterised, the molecules required for migration
      of tolerogenic mononuclear phagocytes (dendritic cells (DC) and macrophages) are
      unknown. We hypothesised that the gut-homing receptor integrin alpha4beta7 is
      required for this process. METHODS: We used a T cell-mediated colitis model to
      study the role of alpha4beta7 in the innate immune compartment. We then performed
      competitive bone marrow (BM) reconstitution experiments to assess the requirement
      of alpha4beta7 in the generation of intestinal retinoic acid (RA)-producing
      CD11c(hi) DC (ALDE(+)DC) and CD64 macrophages. Using mixed BM chimeras we also
      asked whether alpha4beta7 is required to give rise to tolerogenic mononuclear
      phagocytes. RESULTS: Lack of beta7 integrins in the innate immune compartment
      (beta7(-/-)RAG2(-/-) mice) markedly accelerated T cell-mediated colitis, which
      was correlated with lower numbers and frequencies of ALDE(+)DC in mesenteric
      lymph nodes. Consistent with a role of alpha4beta7 in the generation of
      intestinal mononuclear phagocytes, BM cells from beta7(-/-) mice poorly
      reconstituted small intestine ALDE(+)DC and Mphi when compared to their wild type
      counterparts. In addition, mice lacking beta7 integrins in the CD11c(hi)
      compartment showed decreased ability to induce Foxp3(+) T(REG) and IL-10
      producing T cells. CONCLUSIONS: Mice lacking beta7 integrins in the innate immune
      compartment are more susceptible to intestinal inflammation, which is correlated
      with a requirement of beta7 integrins to reconstitute gut mononuclear phagocytes
      with tolerogenic potential.

PMID- 24030489
TI  - Direct spectroscopic characterization of a transitory dirhodium donor-acceptor
      carbene complex.
AB  - A multitude of organic transformations catalyzed by dirhodium(II) (Rh2) complexes
      are thought to proceed via the intermediacy of highly reactive, electrophilic
      carbenoid intermediates that have eluded direct observation. Herein, we report
      the generation of a metastable Rh2-carbenoid intermediate supported by a donor
      acceptor carbene fragment. This intermediate is stable for a period of ~20 hours
      in chloroform solution at 0 degrees C, allowing for an exploration of its
      physical and chemical properties. The Rh=C bond, characterized by vibrational and
      nuclear magnetic resonance spectroscopy, extended x-ray absorption fine structure
      analysis, and quantum-chemical calculations, has weak sigma and pi components.
      This intermediate performs stoichiometric cyclopropanation and C-H
      functionalization reactions to give products that are identical to those obtained
      from analogous Rh2 catalysis. 

PMID- 24030490
TI  - Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex.
AB  - The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we
      report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the
      marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is
      distinct from the proposed major recognition sites for chemokines and the viral
      glycoprotein gp120, providing insights into the mechanism of allosteric
      inhibition of chemokine signaling and viral entry. A comparison between CCR5 and
      CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes,
      suggests that different charge distributions and steric hindrances caused by
      residue substitutions may be major determinants of HIV-1 co-receptor selectivity.
      These high-resolution insights into CCR5 can enable structure-based drug
      discovery for the treatment of HIV-1 infection. 

PMID- 24030492
TI  - Regulation of temperature-responsive flowering by MADS-box transcription factor
      repressors.
AB  - Changes in ambient temperature affect flowering time in plants; understanding
      this phenomenon will be crucial for buffering agricultural systems from the
      effects of climate change. Here, we show that levels of FLM-beta, an
      alternatively spliced form of the flowering repressor FLOWERING LOCUS M, increase
      at lower temperatures, repressing flowering. FLM-beta interacts with SHORT
      VEGETATIVE PHASE (SVP); SVP is degraded at high temperatures, reducing the
      abundance of the SVP-FLM-beta repressor complex and, thus, allowing the plant to
      flower. The svp and flm mutants show temperature-insensitive flowering in
      different temperature ranges. Control of SVP-FLM-beta repressor complex abundance
      via transcriptional and splicing regulation of FLM and posttranslational
      regulation of SVP protein stability provides an efficient, rapid mechanism for
      plants to respond to ambient temperature changes. 

PMID- 24030491
TI  - Distinguishable epidemics of multidrug-resistant Salmonella Typhimurium DT104 in
      different hosts.
AB  - The global epidemic of multidrug-resistant Salmonella Typhimurium DT104 provides
      an important example, both in terms of the agent and its resistance, of a widely
      disseminated zoonotic pathogen. Here, with an unprecedented national collection
      of isolates collected contemporaneously from humans and animals and including a
      sample of internationally derived isolates, we have used whole-genome sequencing
      to dissect the phylogenetic associations of the bacterium and its antimicrobial
      resistance genes through the course of an epidemic. Contrary to current tenets
      supporting a single homogeneous epidemic, we demonstrate that the bacterium and
      its resistance genes were largely maintained within animal and human populations
      separately and that there was limited transmission, in either direction. We also
      show considerable variation in the resistance profiles, in contrast to the
      largely stable bacterial core genome, which emphasizes the critical importance of
      integrated genotypic data sets in understanding the ecology of bacterial zoonoses
      and antimicrobial resistance. 

PMID- 24030493
TI  - Safeguards for cell cooperation in mouse embryogenesis shown by genome-wide
      cheater screen.
AB  - Ensuring cooperation among formerly autonomous cells has been a central challenge
      in the evolution of multicellular organisms. One solution is monoclonality, but
      this option still leaves room for exploitative behavior, as it does not eliminate
      genetic and epigenetic variability. We therefore hypothesized that embryonic
      development must be protected by robust regulatory mechanisms that prevent
      aberrant clones from superseding wild-type cells. Using a genome-wide screen in
      murine induced pluripotent stem cells, we identified a network of genes (centered
      on p53, topoisomerase 1, and olfactory receptors) whose down-regulation caused
      the cells to replace wild-type cells in vitro and in the mouse embryo--without
      perturbing normal development. These genes thus appear to fulfill an unexpected
      role in fostering cell cooperation.

PMID- 24030494
TI  - Structural biology. A new bundle of prospects for blocking HIV-1 entry.

PMID- 24030495
TI  - Microbiology. Sources of antimicrobial resistance.

PMID- 24030496
TI  - In situ observations of interstellar plasma with Voyager 1.
AB  - Launched over 35 years ago, Voyagers 1 and 2 are on an epic journey outward from
      the Sun to reach the boundary between the solar plasma and the much cooler
      interstellar medium. The boundary, called the heliopause, is expected to be
      marked by a large increase in plasma density, from about 0.002 per cubic
      centimeter (cm(-3)) in the outer heliosphere, to about 0.1 cm(-3) in the
      interstellar medium. On 9 April 2013, the Voyager 1 plasma wave instrument began
      detecting locally generated electron plasma oscillations at a frequency of about
      2.6 kilohertz. This oscillation frequency corresponds to an electron density of
      about 0.08 cm(-3), very close to the value expected in the interstellar medium.
      These and other observations provide strong evidence that Voyager 1 has crossed
      the heliopause into the nearby interstellar plasma. 

PMID- 24030497
TI  - Oxidative stress and atrial fibrillation: finding a missing piece to the puzzle.

PMID- 24030498
TI  - Oxidized Ca(2+)/calmodulin-dependent protein kinase II triggers atrial
      fibrillation.
AB  - BACKGROUND: Atrial fibrillation (AF) is a growing public health problem without
      adequate therapies. Angiotensin II and reactive oxygen species are validated risk
      factors for AF in patients, but the molecular pathways connecting reactive oxygen
      species and AF are unknown. The Ca(2+)/calmodulin-dependent protein kinase II
      (CaMKII) has recently emerged as a reactive oxygen species-activated
      proarrhythmic signal, so we hypothesized that oxidized CaMKIIdelta could
      contribute to AF. METHODS AND RESULTS: We found that oxidized CaMKII was
      increased in atria from AF patients compared with patients in sinus rhythm and
      from mice infused with angiotensin II compared with mice infused with saline.
      Angiotensin II-treated mice had increased susceptibility to AF compared with
      saline-treated wild-type mice, establishing angiotensin II as a risk factor for
      AF in mice. Knock-in mice lacking critical oxidation sites in CaMKIIdelta (MM-VV)
      and mice with myocardium-restricted transgenic overexpression of methionine
      sulfoxide reductase A, an enzyme that reduces oxidized CaMKII, were resistant to
      AF induction after angiotensin II infusion. CONCLUSIONS: Our studies suggest that
      CaMKII is a molecular signal that couples increased reactive oxygen species with
      AF and that therapeutic strategies to decrease oxidized CaMKII may prevent or
      reduce AF.

PMID- 24030499
TI  - Innate immune interleukin-1 receptor-associated kinase 4 exacerbates viral
      myocarditis by reducing CCR5(+) CD11b(+) monocyte migration and impairing
      interferon production.
AB  - BACKGROUND: Viral myocarditis follows a fatal course in ~30% of patients.
      Interleukin-1 receptor-associated kinase 4 (IRAK4), a major nodal signal
      transducer in innate immunity, can play a pivotal role in host inflammatory
      response. We sought to determine how IRAK4 modulates inflammation and outcome in
      a mouse model of viral myocarditis. METHODS AND RESULTS: Myocarditis was induced
      after intraperitoneal inoculation of coxsackievirus B3 into C57Bl/6 IRAK4
      deficient mice and their littermate controls. Mortality and viral proliferation
      were markedly reduced in IRAK4(-/-) mice compared with their IRAK4(+/+)
      littermates. Disease resistance of IRAK4(-/-) mice paralleled increased amounts
      of protective heart-infiltrating CCR5(+) monocytes/macrophages and enhanced
      interferon-alpha and interferon-gamma production 2 days after infection.
      Competitive bone marrow chimera demonstrated that intact IRAK4 function inhibited
      heart-specific migration of bone marrow-derived CCR5(+) cells. Mechanistically,
      lack of IRAK4 resulted in interferon regulatory factor 5 homodimerization via
      reduced melanoma differentiation-associated protein 5 degradation and enhanced
      Stat1 and Stat5 phosphorylation. Consequently, antiviral interferon-alpha and
      interferon-gamma production, as well as CCR5(+) cell recruitment, increased,
      whereas the overall proinflammatory response was drastically reduced in the
      absence of IRAK4. CONCLUSIONS: Innate immunity signal transducer IRAK4
      exacerbates viral myocarditis through inhibition of interferon production and
      reduced mobilization of protective CCR5(+) monocytes/macrophages to the heart.
      The combination of IRAK4 inhibitors and antiviral adjuvants may become an
      attractive therapeutic approach against viral myocarditis in the future.

PMID- 24030500
TI  - Early dual versus mono antiplatelet therapy for acute non-cardioembolic ischemic
      stroke or transient ischemic attack: an updated systematic review and meta
      analysis.
AB  - BACKGROUND: Emerging studies suggest that early administration of dual
      antiplatelet therapy may be better than monotherapy for prevention of early
      recurrent stroke and cardiovascular outcomes in acute ischemic stroke and
      transient ischemic attack (TIA). We performed a meta-analysis of randomized,
      controlled trials evaluating dual versus mono antiplatelet therapy for acute
      noncardioembolic ischemic stroke or TIA. METHODS AND RESULTS: We assessed
      randomized, controlled trials investigating dual versus mono antiplatelet therapy
      published up to November 2012 and the CHANCE trial (Clopidogrel in High-risk
      patients with Acute Non-disabling Cerebrovascular Events), for efficacy and
      safety outcomes in adult patients with acute noncardioembolic ischemic stroke or
      TIA with treatment initiated within 3 days of ictus. In total, 14 studies of 9012
      patients were included in the systematic review and meta-analysis. Dual
      antiplatelet therapy significantly reduced risk of stroke recurrence (risk ratio,
      0.69; 95% confidence interval, 0.60-0.80; P<0.001) and the composite outcome of
      stroke, TIA, acute coronary syndrome, and all death (risk ratio, 0.71; 95%
      confidence interval, 0.63-0.81; P<0.001) when compared with monotherapy, and
      nonsignificantly increased risk of major bleeding (risk ratio, 1.35; 95%
      confidence interval, 0.70-2.59, P=0.37). Analyses restricted to the CHANCE Trial
      or the 7 double-blind randomized, controlled trials showed similar results.
      CONCLUSIONS: For patients with acute noncardioembolic ischemic stroke or TIA,
      dual therapy was more effective than monotherapy in reducing risks of early
      recurrent stroke. The results of the CHANCE study are consistent with previous
      studies done in other parts of the world.

PMID- 24030501
TI  - A little good...

PMID- 24030502
TI  - Blood pressure and cognition: factors that may account for their inconsistent
      association.
AB  - BACKGROUND: Studies of hypertension and cognition variously report adverse, null,
      and protective associations. We evaluated evidence supporting three potential
      explanations for this variation: an effect of hypertension duration, an effect of
      age at hypertension initiation, and selection bias due to dependent censoring.
      METHODS: The Normative Aging Study is a prospective cohort study of men in the
      greater Boston area. Participants completed study visits, including hypertension
      assessment, every 3-5 years starting in 1961. Seven hundred fifty-eight of 1,284
      men eligible at baseline completed cognitive assessment between 1992 and 2005; we
      used the mean age-adjusted cognitive test Z score from their first assessment to
      quantify cognition. We estimated how becoming hypertensive and increasing age at
      onset and duration since hypertension initiation affect cognition. We used
      inverse probability of censoring weights to reduce and quantify selection bias.
      RESULTS: A history of hypertension diagnosis predicted lower cognition.
      Increasing duration since hypertension initiation predicted lower mean cognitive
      Z score (-0.02 standard units per year increase [95% confidence interval= -0.04
      to -0.001]), independent of age at onset. Comparing participants with and without
      hypertension, we observed noteworthy differences in mean cognitive score only for
      those with a long duration since hypertension initiation, regardless of age at
      onset. Age at onset was not associated with cognition independent of duration.
      Analyses designed to quantify selection bias suggested upward bias. CONCLUSIONS:
      Previous findings of null or protective associations between hypertension and
      cognition likely reflect the study of persons with short duration since
      hypertension initiation. Selection bias may also contribute to cross-study
      heterogeneity.

PMID- 24030503
TI  - Cadmium in diet and risk of cardiovascular disease in women.
AB  - BACKGROUND: The toxic metal cadmium is suggested to increase the risk of
      cardiovascular disease, but only one incidence study has explored this
      association. We evaluated the association between quartiles of food frequency
      questionnaire-based estimates of cadmium exposure from food (the predominant
      source of exposure to the metal) and incident cardiovascular disease and its
      subtypes. METHODS: From the population-based Swedish Mammography cohort, 33,333
      women were followed prospectively from baseline (1997) through 2010. We estimated
      relative risks (RRs) with 95% confidence intervals (CIs) using Cox proportional
      hazard models. RESULTS: During 12 years of follow-up, we identified 3155 incident
      cases of total cardiovascular disease (1322 cases of myocardial infarction and
      1833 cases of total stroke [1485 ischemic and 208 hemorrhagic stroke]). Dietary
      cadmium exposure was not associated with risk of total cardiovascular disease,
      myocardial infarction, or total stroke or its subtypes. For total cardiovascular
      disease, the multivariable-adjusted RR comparing the highest quartile of cadmium
      exposure with the lowest was 0.96 (95% CI = 0.85-1.09). The corresponding RRs
      were 1.07 (0.88-1.29) for myocardial infarction, 0.90 (0.76-1.05) for total
      stroke, 0.89 (0.74-1.06) for ischemic stroke, and 1.11 (0.68-1.80) for
      hemorrhagic stroke. CONCLUSIONS: Our study lends no support to an overall
      association between low-level exposure to cadmium via food and incident
      cardiovascular disease.

PMID- 24030504
TI  - Epigenetics: Showing a more sensitive side.

PMID- 24030505
TI  - Mouse models: Novel in vivo RNAi screen in mice.

PMID- 24030506
TI  - Question 1: is sedation necessary for MRI in an infant?

PMID- 24030507
TI  - Towards evidence based medicine for paediatricians.

PMID- 24030508
TI  - Question 2: Would systemic steroids be useful in the management of Stevens
      Johnson syndrome?

PMID- 24030510
TI  - Plasma membrane organization and function: moving past lipid rafts.
AB  - "Lipid raft" is the name given to the tiny, dynamic, and ordered domains of
      cholesterol and sphingolipids that are hypothesized to exist in the plasma
      membranes of eukaryotic cells. According to the lipid raft hypothesis, these
      cholesterol- and sphingolipid-enriched domains modulate the protein-protein
      interactions that are essential for cellular function. Indeed, many studies have
      shown that cellular levels of cholesterol and sphingolipids influence plasma
      membrane organization, cell signaling, and other important biological processes.
      Despite 15 years of research and the application of highly advanced imaging
      techniques, data that unambiguously demonstrate the existence of lipid rafts in
      mammalian cells are still lacking. This Perspective summarizes the results that
      challenge the lipid raft hypothesis and discusses alternative hypothetical models
      of plasma membrane organization and lipid-mediated cellular function. 

PMID- 24030511
TI  - Memories of Hugh E. Huxley (1924-2013).

PMID- 24030513
TI  - Mechanism of chelation enhanced fluorescence in complexes of cadmium(II), and a
      possible new type of anion sensor.
AB  - The Cd(II) complex of adpa (N-(9-anthracenylmethyl)-N,N-di-(picolyl)amine) in
      MeOH-H2O has increased fluorescence intensity with [Cl(-)], a new type of anion
      sensor. The structure of [Cd(adpa)(NO3)2] has a proposed fluorescence-quenching
      pi-contact between Cd and the fluorophore, while the Cl in [Cd(adpa)Cl2] disrupts
      the pi-contact, restoring fluorescence.

PMID- 24030512
TI  - White blood cell count in young adulthood and coronary artery calcification in
      early middle age: coronary artery risk development in young adults (CARDIA)
      study.
AB  - White blood cell (WBC) count is associated with incident coronary heart disease
      (CHD). Data are sparse regarding its association in young adults with future
      coronary artery calcification (CAC). Our study was conducted among coronary
      artery risk development in young adults (CARDIA) participants (n=3,094). We
      examined the association between baseline (Y0) WBC counts and CHD risk factors
      using linear regression models. We further assessed prospective associations
      between Y0 WBC and inflammatory biomarkers during the follow-up, and the presence
      of CAC 15 and 20 years later. In total, 272 and 566 subjects had CAC scores>0 at
      year (Y) 15 and Y20, respectively. Baseline total WBC counts were cross
      sectionally associated with SBP, BMI, and smoking, or HDL-cholesterol (p<=0.01)
      at Y0, and prospectively associated with C-reactive protein at Y7, Y15, and Y20,
      and fibrinogen at Y5 and Y20 (p<0.01). After adjustment for potential confounding
      factors, baseline neutrophil count was borderline associated with CAC presence 15
      years later (OR=1.18 per unit, 95% CI 1.00-1.44) and total WBC (OR=1.07, 95% CI
      0.96-1.19) or eosinophil (OR=1.12, 95%CI 1.00-1.25) was borderline associated
      with CAC presence at Y20. Baseline total WBC counts in young adults was
      associated prospectively with CAC presence 20 years later after adjusting for
      age, sex, and race. Results are attenuated when other risk factors are accounted
      for. Our results suggest the possible early involvement of WBC, particularly
      eosinophils, in the early stages of atherosclerosis.

PMID- 24030514
TI  - Microvascular abnormality in schizophrenia as shown by retinal imaging.
AB  - OBJECTIVE: Retinal and cerebral microvessels are structurally and functionally
      homologous, but unlike cerebral microvessels, retinal microvessels can be
      noninvasively measured in vivo by retinal imaging. The authors tested the
      hypothesis that individuals with schizophrenia exhibit microvascular abnormality
      and evaluated the utility of retinal imaging as a tool for schizophrenia
      research. METHOD: Participants were members of the Dunedin Study, a population
      representative cohort followed from birth with 95% retention. Study members
      underwent retinal imaging at age 38. The authors assessed retinal arteriolar and
      venular caliber for all members of the cohort, including individuals who
      developed schizophrenia. RESULTS: Study members who developed schizophrenia were
      distinguished by wider retinal venules, suggesting microvascular abnormality
      reflective of insufficient brain oxygen supply. Analyses that controlled for
      confounding health conditions suggested that wider retinal venules are not simply
      an artifact of co-occurring health problems in schizophrenia patients. Wider
      venules were also associated with a dimensional measure of adult psychosis
      symptoms and with psychosis symptoms reported in childhood. CONCLUSIONS: The
      findings provide initial support for the hypothesis that individuals with
      schizophrenia show microvascular abnormality. Moreover, the results suggest that
      the same vascular mechanisms underlie subthreshold symptoms and clinical disorder
      and that these associations may begin early in life. These findings highlight the
      promise of retinal imaging as a tool for understanding the pathogenesis of
      schizophrenia.

PMID- 24030515
TI  - Diurnal changes of lower leg volume in obese and non-obese subjects.
AB  - BACKGROUND/AIM: Obesity is a risk factor for chronic venous disease. However, the
      mechanisms behind this association are poorly understood. We tested the
      hypothesis that obese subjects have a higher diurnal leg volume increase compared
      with non-obese subjects. METHODS: In this prospective cohort study including
      obese (body mass index, BMI >=30 kg m(-)(2)) and non-obese (BMI <=25 kg m(-)(2))
      subjects without venous insufficiency, lower leg volume was assessed by
      optoelectronic volumetry in the morning and in the evening. All subjects
      underwent duplex ultrasound and light reflection rheography (venous pump power
      and venous refill time, VRT) to investigate lower extremity venous function. A
      pedometer was carried between the morning and evening visit to assess the daily
      number of footsteps. A backward multivariable linear regression model was used to
      determine factors associated with diurnal lower leg volume increase. RESULTS:
      Forty-two limbs in 24 obese subjects and 29 limbs in 15 non-obese subjects were
      analyzed. Obese subjects had larger common femoral vein diameters (17.1+/-2.4 vs
      15.5+/-2.4 mm, P<0.01) and slower peak, mean and minimal velocities (25.1+/-10.6
      vs 44.3+/-14.3 cm s(-1); 6.8+/-2.4 vs 12.7+/-5.6 cm s(-1); -0.2+/-6.4 vs -6.3+/
      11.9 cm s(-1); P<0.01 for all) than non-obese subjects. VRT was shorter in obese
      subjects (40.5+/-15.0 vs 51.0+/-12.1 s, P<0.01) and decreased significantly in
      the course of the day only in obese subjects (P<0.01). Obesity, male gender, CEAP
      (Clinical-Etiology-Anatomy-Pathophysiology) class, total time between the two
      visits and difference between morning and evening VRT were positively associated
      with higher lower leg volume increase; morning VRT and the total number of
      footsteps showed a negative association (P<0.04 for all). CONCLUSION: Obesity was
      found to be an independent predictor of higher diurnal leg volume increase. One
      potential mechanism is a progressive failure of venous valve function in the
      course of the day in obese subjects.

PMID- 24030516
TI  - Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular
      functions and responses to leptin.
AB  - OBJECTIVE: We examined whether deficiency of Src homology 2 containing
      phosphatase (Shp2) signaling in forebrain neurons alters metabolic and
      cardiovascular regulation under various conditions and if it attenuates the
      anorexic and cardiovascular effects of leptin. We also tested whether forebrain
      Shp2 deficiency alters blood pressure (BP) and heart rate (HR) responses to acute
      stress. DESIGN: Forebrain Shp2(-/-) mice were generated by crossing
      Shp2(flox/flox) mice with CamKIIalpha-cre mice. At 22-24 weeks of age, the mice
      were instrumented for telemetry for measurement of BP, HR and body temperature
      (BT). Oxygen consumption (VO2), energy expenditure and motor activity were
      monitored by indirect calorimetry. RESULTS: Shp2/CamKIIalpha-cre mice were
      heavier (46+/-3 vs 32+/-1 g), hyperglycemic, hyperleptinemic, hyperinsulinemic
      and hyperphagic compared to Shp2(flox/flox) control mice. Shp2/CamKIIalpha-cre
      mice exhibited reduced food intake responses to fasting/refeeding and impaired
      regulation of BT when exposed to 15 and 30  degrees C ambient temperatures.
      Despite being obese and having many features of metabolic syndrome,
      Shp2/CamKIIalpha-cre mice had similar daily average BP and HR compared to
      Shp2(flox/flox) mice (112+/-2 vs 113+/-1 mm Hg and 595+/-34 vs 650+/-40 b.p.m.),
      but exhibited increased BP and HR responses to cold exposure and acute air-jet
      stress test. Leptin's ability to reduce food intake and to raise BP were markedly
      attenuated in Shp2/CamKIIalpha-cre mice. CONCLUSION: These results suggest that
      forebrain Shp2 signaling regulates food intake, appetite responses to caloric
      deprivation and thermogenic control of body temperature during variations in
      ambient temperature. Deficiency of Shp2 signaling in the forebrain is associated
      with augmented cardiovascular responses to cold and acute stress but attenuated
      BP responses to leptin.

PMID- 24030517
TI  - The challenge of a 2-year follow-up after intervention for weight loss in primary
      care.
AB  - BACKGROUND: Many weight loss programmes show short-term success, but long-term
      data in larger studies are scarce, especially in community settings. Attrition is
      common and complicates the interpretation of long-term outcomes. OBJECTIVE: To
      investigate 2-year outcomes and explore issues of attrition and missing data.
      SUBJECTS: A total of 772 overweight and obese adults recruited by primary care
      practices in Australia, Germany and the UK and randomised to a 12-month weight
      loss intervention delivered in a commercial programme (CP) or in standard care
      (SC). MEASUREMENT: Weight change from 0-24 and 12-24 months including measured
      weights only and measured and self-reported weights, using last observation
      carried forward (LOCF), baseline observation carried forward (BOCF), completers
      only and missing-at-random (MAR) analyses. RESULTS: A total of 203 participants
      completed the 24-month visit. Using measured weights only, there was a trend for
      greater 24-month weight loss in CP than in SC, but the difference was only
      statistically significant in the LOCF and BOCF analyses: LOCF: -4.14 vs -1.99 kg,
      difference adjusted for centre -2.08 kg, P<0.001; BOCF: -1.33 vs -0.74 kg,
      adjusted difference -0.60 kg, P=0.032; completers: -4.76 vs -2.99 kg, adjusted
      difference -1.53 kg, P=0.113; missing at random: -3.00 vs -1.94 kg, adjusted
      difference -1.04 kg, P=0.150. Both groups gained weight from 12-24 months and
      weight regain was significantly (P<0.001) greater for CP than for SC in all
      analysis approaches. Inclusion of self-reported weights from a further 138
      participants did not change the interpretation of the findings. CONCLUSION:
      Initial weight loss was poorly maintained during the no-intervention follow-up,
      but both groups did have lower weight over the 24 months. Attrition was high in
      both groups, and assumptions about missing data had considerable impact on the
      magnitude and statistical significance of treatment effects. It is vital that
      trials on weight loss interventions consider the plausibility of these
      differences in an analytical approach when interpreting research findings and
      comparing data between studies.

PMID- 24030518
TI  - Satiety and energy intake after single and repeated exposure to gel-forming
      dietary fiber: post-ingestive effects.
AB  - BACKGROUND: Viscous or gel-forming dietary fibers can increase satiety by a more
      firm texture and increased eating time. Effects of viscous or gel-forming fibers
      on satiety by post-ingestive mechanisms such as gastric emptying, hormonal
      signals, nutrient absorption or fermentation are unclear. Moreover, it is unclear
      whether the effects persist after repeated exposure. OBJECTIVE: To investigate
      satiety and energy intake after single and repeated exposure to gelled fiber by
      post-ingestive mechanisms. DESIGN: In a two-arm crossover design, 32 subjects (24
      female subjects, 21+/-2 y, BMI 21.8+/-1.9 kg m(-2)) consumed test foods once
      daily for 15 consecutive days, with 2 weeks of washout. Test foods were
      isocaloric (0.5 MJ, 200 g) with either 10 g gel-forming pectin or 3 g gelatin and
      2 g starch, matched for texture and eating time. Hourly satiety ratings, ad
      libitum energy intake and body weight were measured on days 1 (single exposure)
      and 15 (repeated exposure). In addition, hourly breath hydrogen, fasting glucose,
      insulin, leptin and short-chain fatty acids were measured. RESULTS: Subjects
      rated hunger, desire to eat and prospective intake about 2% lower (P<0.015) and
      fullness higher (+1.4%; P=0.041) when they received pectin compared with control.
      This difference was similar after single and repeated exposure (P>0.64). After
      receiving pectin, energy intake was lower (-5.6%, P=0.012) and breath hydrogen
      was elevated (+12.6%, P=0.008) after single exposure, but not after repeated
      exposure. Fasting glucose concentrations were higher both after single and
      repeated exposure to pectin (+2.1%, P=0.019). Body weight and concentrations of
      insulin, leptin and short-chain fatty acids did not change during the study.
      CONCLUSIONS: Gelled pectin can increase satiety and reduce energy intake by post
      ingestive mechanisms. Although the effects were small, the effects on satiety
      were consistent over time, whereas the effects on energy intake reduction were
      not.

PMID- 24030520
TI  - In response.

PMID- 24030519
TI  - Effect of pitch-space correspondence on sound-induced visual motion perception.
AB  - The brain tends to associate specific features of stimuli across sensory
      modalities. The pitch of a sound is for example associated with spatial elevation
      such that higher-pitched sounds are felt as being "up" in space and lower-pitched
      sounds as being "down." Here we investigated whether changes in the pitch of
      sounds could be effective for visual motion perception similar to those in the
      location of sounds. We demonstrated that only sounds that alternate in up/down
      location induced illusory vertical motion of a static visual stimulus, while
      sounds that alternate in higher/lower pitch did not induce this illusion. The
      pitch of a sound did not even modulate the visual motion perception induced by
      sounds alternating in up/down location. Interestingly, though, sounds alternating
      in higher/lower pitch could become a driver for visual motion if they were paired
      in a previous exposure phase with vertical visual apparent motion. Thus, only
      after prolonged exposure, the pitch of a sound became an inducer for upper/lower
      visual motion. This occurred even if during exposure the pitch and location of
      the sounds were paired in an incongruent fashion. These findings indicate that
      pitch-space correspondence is not so strong to drive or modulate visual motion
      perception. However, associative exposure could increase the saliency of pitch
      space relationships and then the pitch could induce visual motion perception by
      itself. 

PMID- 24030522
TI  - Disruption of pro-oxidant and antioxidant systems with elevated expression of the
      ubiquitin proteosome system in the cachectic heart muscle of nude mice.
AB  - BACKGROUND: Current research into the mechanisms of organ atrophy associated with
      cancer cachexia have centred on the loss of skeletal muscle, as it is one of the
      most profound physical changes of the disease. However, many patients with cancer
      cachexia also experience significant atrophy of the heart. The mechanisms causing
      cardiac tissue wastage in cancer cachexia are largely unknown. However, it is
      believed to involve a number of molecular interactions between the tumour and
      host. Increased levels of oxidative stress have been found in cancer cachectic
      skeletal muscle and has been linked to the activation of the ubiquitin proteosome
      system (UPS). The aim of the current study was to examine the role of oxidative
      stress and the UPS in the hearts of mice with cancer cachexia. METHODS: Oxidative
      damage to DNA (8-OH-2dG), mRNA levels of the ROS-producing enzymes NADPH oxidase
      (NOX), and xanthine oxidase (XDH), the antioxidant enzyme superoxide dismutase
      (SOD) and key components of the UPS was measured in the heart of mice with cancer
      cachexia. Protein expression levels of NOX enzyme subunits and SOD enzyme
      activity was also measured in the same heart samples. RESULTS: 8-OH-2dG levels
      were 1.5-fold higher in the heart of mice with cancer cachexia, and this was
      associated with a 1.7-fold lower level of NOX2 mRNA and twofold higher XDH mRNA
      in the same hearts. Cancer cachexia was also associated with a 1.5-fold lower
      level of SOD activity in the heart. Accompanying these pro- and antioxidant
      differences was a significantly higher level of mRNA for the key UPS elements
      MURF-1 (4.3=fold) and MAFbx (3.8-fold) in the hearts of mice with cancer
      cachexia. CONCLUSIONS: The current study demonstrated that cardiac atrophy of
      cachectic mice is associated with oxidative damage to DNA in the myocardium. The
      higher levels of XDH mRNA in cachectic hearts suggest that xanthine oxidase may
      have an important role to play in producing oxidative stress. It appears that the
      combination of higher XDH expression and lower SOD enzyme activity are key
      contributors to oxidative stress and cardiac tissue damage in cancer-induced
      cardiac atrophy. Oxidative stress in the myocardium as with skeletal muscle may
      also induce increased expression of the E3 ligases MURF-1 and MAFbx as seen in
      this study.

PMID- 24030524
TI  - Neoplasia yield and colonoscopic workload of surveillance regimes for colorectal
      cancer in colitis patients: a retrospective study comparing the performance of
      the updated AGA and BSG guidelines.
AB  - BACKGROUND: Due to the increased risk of colorectal cancer, colonoscopic
      surveillance is recommended for patients with ulcerative and Crohn's colitis.
      Because surveillance intervals differ considerably between the recently updated
      American Gastroenterological Association (AGA) and British Society of
      Gastroenterology (BSG) guidelines, we compared the neoplasia yield and
      colonoscopic workload of these guidelines. METHODS: Patients with inflammatory
      bowel disease undergoing surveillance were identified using medical records.
      Patients were stratified according to the BSG and AGA guidelines, and
      corresponding colonoscopic workload was calculated based on the risk factors
      present during follow-up. The incidence of colitis-associated neoplasia (CAN),
      defined as a low-grade dysplasia in flat mucosa or a non-adenoma-like mass, high
      grade dysplasia, or colorectal cancer was compared between the risk groups of
      either guidelines. RESULTS: In total, 1018 patients with inflammatory bowel
      disease who underwent surveillance were identified. Using the AGA surveillance
      intervals, 64 patients (6%) were assigned to annual and 954 patients (94%) to
      biannual surveillance, resulting in 541 colonoscopies per year. The yield of CAN
      was 5.3% and 20.3% in the low- and high-risk groups, respectively (P = 0.02).
      Using the BSG surveillance intervals, 204 patients received surveillance annually
      (20%), 393 patients every 3 years (39%), and 421 patients every 5 years (41%),
      resulting in 420 colonoscopies per year, which is 22% lower than the AGA
      guidelines. The yield of CAN was 3.6%, 6.9%, and 10.8%, for the low-,
      intermediate-, and high-risk groups, respectively (P = 0.26). CONCLUSIONS:
      Although the BSG surveillance intervals offer the advantage of a lower
      colonoscopic workload, the risk stratification of the AGA seems superior in
      distinguishing patients at higher risk of CAN.

PMID- 24030523
TI  - Proton pump inhibitors and clopidogrel: an association to avoid?
AB  - Dual antiplatelet therapy with aspirin and clopidogrel reduces cardiovascular
      events following an acute coronary syndrome or stent implantation, but the
      associated increased risk of gastro-intestinal bleeding often leads to the co
      administration of proton pump inhibitors (PPIs). PPIs have been shown to decrease
      antiplatelet effects of clopidogrel ex vivo, raising concerns about the
      cardiovascular safety of this drug combination. Clinical trials investigating PPI
      clopidogrel interactions have provided conflicting results and are all subject to
      methodological critiques. The much desired and much needed prospective, double
      bind, randomized, placebo-controlled trials with adequate follow-up and sample
      size have not yet been performed. Indeed, the Clopidogrel and the Optimization of
      GI Events Trial, which would have had such characteristics, was stopped
      prematurely. As a consequence, the question of the PPI-clopidogrel interaction is
      still unresolved, and clinical consequences cannot be excluded. At this time such
      combination therapy should, therefore, be provisionally advocated only for
      patients at high risk of bleeding (prior upper gastro-intestinal bleeding,
      advanced age, concomitant use of warfarin, steroidal or non-steroidal anti
      inflammatory drugs and Helicobacter pylori infection) and avoiding PPIs with
      strong affinity for cytochrome CYP2C19, such as omeprazole and esomeprazole. 

PMID- 24030525
TI  - Chloride channel ClC-2 is a key factor in the development of DSS-induced murine
      colitis.
AB  - BACKGROUND: Previously, it was shown that the chloride channel ClC-2 modulates
      intestinal tight junction (TJ) barrier function. The aim of the present study was
      to investigate the role of ClC-2 in epithelial barrier function and recovery in
      the event of epithelial injury. METHODS: The role of ClC-2 was investigated in TJ
      barrier function in dextran sodium sulfate (DSS)-induced colitis in ClC-2
      knockout mice and ClC-2 knockdown intestinal Caco-2 cells. Barrier function was
      measured electrophysiologically and by transepithelial mannitol fluxes. Selected
      TJ and associated proteins were Western blotted, cytokines were measured using
      quantitative PCR, and human colonic biopsies were examined with
      immunohistochemistry. RESULTS: ClC-2 mice had a higher disease activity index,
      higher histological scores, and increased paracellular permeability compared with
      wild-type mice when treated with DSS. DSS-treated ClC-2 mice had increased
      claudin-2 expression, greater loss of occludin in the membrane, increased
      association of occludin with caveolin-1, and significantly increased tumor
      necrosis factor-alpha and interleukin-1beta messenger RNA. ClC-2 knockdown in
      human intestinal Caco-2 cells resulted in a greater loss of epithelial resistance
      in the event of epithelial injury. The restoration of colonic barrier function
      after DSS colitis was delayed in ClC-2 mice. In human colonic biopsies, the
      protein and messenger RNA expression of ClC-2 was found to be reduced in patients
      with ulcerative colitis. CONCLUSIONS: ClC-2 plays a critical role in experimental
      colitis in that its absence increases disease activity, reduces barrier function
      and recovery, and perturbs TJs. Furthermore, ClC-2 expression is markedly reduced
      in the colon of human patients with ulcerative colitis.

PMID- 24030528
TI  - Departure: Max Beckmann.

PMID- 24030529
TI  - Leptin deficiency promotes central sleep apnea in patients with heart failure.
AB  - BACKGROUND: Leptin-deficient animals hyperventilate. Leptin expression by
      adipocytes is attenuated by atrial natriuretic peptide (ANP). Increased
      circulating natriuretic peptides (NPs) are associated with an increased risk of
      central sleep apnea (CSA). This study tested whether serum leptin concentration
      is inversely correlated to NP concentration and decreased in patients with heart
      failure (HF) and CSA. METHODS: Subjects with HF (N = 29) were studied by
      measuring leptin, NPs, CO2 chemosensitivity (Deltaminute ventilation
      [V.e]/Deltapartial pressure of end-tidal CO2 [Petco2]), and ventilatory
      efficiency (V.e/CO2 output [V.co2]) and were classified as CSA or no sleep
      disordered breathing by polysomnography. CSA was defined as a central apnea
      hypopnea index >= 15. The Student t test, Mann-Whitney U test, and logistic
      regression were used for analysis, and data were summarized as mean +/- SD; P <
      .05 was considered significant. RESULTS: Subjects with CSA had higher ANP and
      brain natriuretic peptide (BNP) concentrations (P < .05), DeltaV.e/DeltaPetco2
      (2.39 +/- 1.03 L/min/mm Hg vs 1.54 +/- 0.35 L/min/mm Hg, P = .01), and V.e/V.co2
      (43 +/- 9 vs 34 +/- 7, P < .01) and lower leptin concentrations (8 +/- 10.7 ng/mL
      vs 17.1 +/- 8.8 ng/mL, P < .01). Logistic regression analysis (adjusted for age,
      sex, and BMI) demonstrated leptin (OR = 0.07; 95% CI, 0.01-0.71; P = .04) and BNP
      (OR = 4.45; 95% CI, 1.1-17.9; P = .05) to be independently associated with CSA.
      CONCLUSIONS: In patients with HF and CSA, leptin concentration is low and is
      inversely related to NP concentration. Counterregulatory interactions of leptin
      and NP may be important in ventilatory control in HF.

PMID- 24030530
TI  - Long-term compliance of the Velumount(r) palatal device.
AB  - OBJECTIVES: The aim of this study was to investigate the long-term compliance of
      the Velumount(r) palatal device. METHODS: This was a cohort study: 46 patients
      who received a Velumount device three years previously were enrolled. A
      questionnaire was sent to all patients. The data of 43 patients (93%) could be
      evaluated. RESULTS: Seventeen (40%) patients used the Velumount device regularly
      (>5 nights per week). However, 24 (56%) abandoned its use, 1 (2%) used it only
      occasionally (1-2 nights/week) and 1 (2%) used it only on special occasions. The
      main reasons for discontinuing Velumount were gag reflex (36%) and foreign body
      sensation (20%). CONCLUSIONS: The long-term compliance of the Velumount is 40%.
      Those patients who tolerate Velumount well use it regularly at least 5 nights per
      week. The Velumount palatal device is a valuable treatment option in counseling
      for patients with primary snoring or mild obstructive sleep apnea.

PMID- 24030531
TI  - SOX4 expression is closely associated with differentiation and lymph node
      metastasis in oral squamous cell carcinoma.
AB  - SOX4 is a member of the SOX family of transcription regulators. In recent years,
      SOX4 was shown to be overexpressed in cancers of various organs and related to
      epithelial-mesenchymal transition, which is a metastatic factor. This study was
      the first to investigate correlations between SOX4 expression levels and the
      clinicopathologic factors of oral squamous cell carcinoma (OSCC). We analyzed
      SOX4 expression levels in 50 patients with OSCC using immunohistochemistry. All
      samples expressed the SOX4 protein and elevated SOX4 expression was significantly
      correlated with gender, T status, and stage levels. The expression level of SOX4
      in primary foci of poorly differentiated OSCC was higher than that of well
      differentiated OSCC, which indicated that SOX4 expression is associated with the
      differentiation of OSCC. However, regardless of the differentiation level in the
      primary focus, SOX4 expression levels were found to be very high in the
      metastatic focus. Furthermore, SOX4 expression in metastatic foci was
      significantly suppressed by neoadjuvant therapy. These results indicate that
      undifferentiated OSCC cells expressing SOX4 are more likely to metastasize and
      neoadjuvant therapy including chemoradiation therapy may have some effect in
      metastatic prevention. 

PMID- 24030532
TI  - NGF and VEGF effects on retinal ganglion cell fate: new evidence from an animal
      model of diabetes.
AB  - PURPOSE: To investigate if the survival effects of nerve growth factor (NGF)
      eyedrops on retinal ganglion cell (RGCs) are related to vascular endothelial
      growth factor (VEGF) in a rat model of diabetic retinopathy. METHODS: Diabetes
      was induced in adult rats by streptozotocin injection and changes in the NGF/TrkA
      and VEGF retina levels were related to the progression of RGC loss. Diabetic rats
      were subjected to administration of NGF eyedrops or intraocular injection of anti
      NGF antibody. All morphologic, immunohistochemical, and biochemical analyses were
      performed on whole retinas dissected after 7 or 11 weeks after diabetes
      induction. RESULTS: Diabetes was successfully induced in rats as shown by
      glycemic levels >250 mg/dL. The NGF levels increased in diabetic retinas at 7
      weeks and decreased at 11 weeks, while VEGF levels increased at all time points.
      The RGC loss in diabetic retinopathy worsened with anti-NGF administration, which
      did not alter retina VEGF levels significantly. Administration of NGF eyedrops
      restored TrkA levels in the retina, and protected RGCs from degeneration without
      influencing VEGF levels. CONCLUSIONS: The early increase of NGF in diabetic
      retina might be an endogenous response for protecting RGCs from degeneration.
      This protective mechanism is impaired at 11 weeks following diabetes induction,
      and results in a marked RGC degeneration that is improved by exogenous NGF
      administration and worsened by anti-NGF. The observed NGF-induced neuroprotection
      on damaged RGCs was not associated with changes in VEGF retina levels, which were
      constantly high in diabetic rats and were not altered by anti-NGF administration.

PMID- 24030533
TI  - Intraoperative and postoperative corneal thickness change after collagen
      crosslinking therapy.
AB  - PURPOSE: To assess intraoperative and postoperative changes in corneal thickness
      subsequent to riboflavin-UVA (collagen crosslinking [CXL]) treatment. METHODS:
      Forty-one eyes of 41 patients (mean age 27.97 +/- 6.97 years) were treated with
      CXL technique. During treatment, isotonic riboflavin was instilled and corneal
      thickness measurements were obtained at the cornea apex, the thinnest point, and
      the pupil center at 15 and 30 minutes, then 3 days, 1 week, and 1, 3, 6, and 12
      months after surgery using Pentacam HR and an ultrasound pachymeter. RESULTS: A
      decrease in corneal thickness was detected 15 minutes intraoperatively with a
      value of 108.95 +/- 48.6 um, and 112.35 +/- 47.3 um at 30 minutes (p<0.001).
      Three days after the operation, no deviation was found from the initial values (p
      = 0.17). No further changes were detected during the follow-up period.
      CONCLUSIONS: Isotonic riboflavin solution used during CXL treatment resulted in a
      significant decrease in corneal thickness, but its effect had disappeared by
      postoperative day 3.

PMID- 24030534
TI  - Fuchs' superficial marginal keratitis managed with circumferential marginal
      corneoscleral lamellar patch graft.
AB  - PURPOSE: To report a case of Fuchs' superficial marginal keratitis managed with
      circumferential marginal corneoscleral lamellar patch graft. METHODS:
      Interventional case report. RESULTS: A 34-year-old man presented with several
      years' history of ill-defined symptoms of binocular ocular irritation associated
      with vision loss, mostly in the left eye. A superior marginal corneal thinning
      was found at biomicroscopy of the left eye, with 2 finely vascularized
      descemetoceles, and a gray epithelial demarcation line without lipid infiltrates.
      The right eye was clinically normal. Anterior segment optical coherence
      tomography demonstrated an important corneal thinning from the 7 o'clock to 3
      o'clock positions, without scleral involvement. A circumferential marginal
      corneoscleral lamellar patch graft was done involving 3 mm of sclera and 3 mm of
      cornea. CONCLUSIONS: Fuchs' superficial marginal keratitis is a rare entity,
      mostly affecting young adults. It should be considered part of a spectrum of
      corneal thinning disorders, together with Terrien's marginal degeneration.
      Definitive treatment with a marginal corneoscleral lamellar patch graft with or
      without conjunctival autograft is suggested.

PMID- 24030535
TI  - The effect of an artificial tear combining hyaluronic acid and tamarind seeds
      polysaccharide in patients with moderate dry eye syndrome: a new treatment for
      dry eye.
AB  - PURPOSE: Synergistic interactions between hyaluronic acid (HA) and tamarind seed
      polysaccharide (TS-polysaccharide) have been demonstrated by means of nuclear
      magnetic resonance spectroscopy. This study was designed to investigate the
      potential clinical benefit of a combination of HA and TS-polysaccharide in
      managing dry eye disease (DED). METHODS: A total of 49 subjects with moderate
      DED, confirmed by Ocular Surface Disease Index (OSDI) questionnaire score between
      10 and 25, tear break-up time (BUT) <10 seconds, or Schirmer I test <5.5 mm after
      5 minutes, and lissamine green staining of the ocular surface >2 according to
      National Eye Institute score system, were enrolled into this multicenter,
      randomized, double-masked study to receive either combination of HA and TS
      polysaccharide or carmellose sodium for 3 months, both instilled 4 times per day.
      The assessments included OSDI questionnaire, tear film stability (BUT), tear
      production (Schirmer I test), and corneal and conjunctival staining. RESULTS:
      Patients treated with HA and TS-polysaccharide showed a statistically significant
      improvement in the OSDI score at the end of the study compared to the baseline
      and control groups. The HA and TS-polysaccharide and carmellose sodium were
      equally effective in reducing BUT and the extent of injury assessed by corneal
      and conjunctival staining. Non-significant changes were recorded for Schirmer I
      test. CONCLUSIONS: Based on the results of this clinical trial, the combination
      of HA and TS-polysaccharide appears to be effective in improving the symptoms of
      dry eye, opening new scenarios in possible treatment of the disease by combining
      different molecules.

PMID- 24030536
TI  - Bilateral superior oblique palsy: etiology and therapeutic options.
AB  - PURPOSE: To study the causes of bilateral superior oblique palsy (BSOP),
      treatment with botulinum toxin and/or surgery, and outcome of treatment. METHODS:
      This was an 11-year retrospective study of patients with BSOP treated with
      injections of botulinum toxin (Botox), surgery, or both. Treatment was considered
      successful when anomalous head turn and diplopia in primary gaze position and
      downgaze resolved. RESULTS: Bilateral superior oblique palsy was diagnosed in 12
      patients (8 male; mean age, 29.5 years). Palsy was secondary to a neoplasm in 3
      cases and to head trauma in 2. In 2 cases, it was ischemic, in 2 it was
      congenital; the remaining cases were iatrogenic (hydrocephalus secondary to
      meningitis, 1), hemorrhagic (1), and idiopathic (1). The clinical manifestations
      recorded were diplopia (10), anomalous head posture (9), V pattern (12),
      subjective excyclotorsion (8), and objective excyclotorsion (6). Recovery was
      spontaneous in 1 case with neoplastic disease. Botox was injected in 8 cases
      (inferior oblique and/or inferior rectus muscles [successful in 2]), and
      subsequent surgery was required in 6. Two patients underwent surgery without
      prior injection of Botox. The most common surgical technique was recession of the
      inferior oblique muscle (6 patients), either as the only operation or associated
      with other procedures. The final result was good in 72.72% (8/11). Mean follow-up
      was 62.6 months (range 9-99 months). CONCLUSIONS: Causes of BSOP were varied
      (most frequently neoplastic). Botox was effective as the only treatment in 25%
      (2/8). Outcome was good in a high percentage of cases with Botox, surgery, or
      both.

PMID- 24030537
TI  - Prognostic factors and visual outcomes of ruptured and lacerated globe injuries.
AB  - PURPOSE: To identify prognostic factors related to ruptured and lacerated globes
      and compare the visual outcomes of these 2 mechanisms of injury. METHODS: Medical
      records of patients with open-globe injuries referred to the Goldschleger Eye
      Institute between 2004 and 2010 were reviewed. Clinical parameters were
      summarized as defined by the ocular trauma score (OTS). All cases were classified
      as either ruptured or lacerated globes and a statistical analysis was performed
      in order to identify prognostic factors. RESULTS: Medical records of 73 patients
      (55 male) were reviewed. Mean age of male injured patients was 33 years and of
      female injured patients was 64 years. Thirty-three percent of injuries were
      classified as ruptured globes. Males were mostly injured by a lacerating
      mechanism, compared to females (79.6% and 33.3%, respectively; p = 0.01). Mean
      logMAR at presentation after lacerated and ruptured globes was 1.42 +/- 1.01 and
      2.02 +/- 0.91, respectively. Mean logMAR at the final follow-up visit after
      lacerated and ruptured globes was 0.65 +/- 0.85 and 1.69 +/- 1.10, respectively.
      Mean logMAR of the lacerated globes improved to a better extent compared to the
      ruptured ones (p = 0.046). The OTS was found to be a significant predictor of
      final mean logMAR for the lacerated globes (p<0.001), whereas mean logMAR at
      presentation was found to be the only predictive measure for ruptured globes
      (p<0.001). CONCLUSIONS: Ruptured and lacerated globes differ from each other in
      regard to prognostic factors and visual outcomes. We recommend distinguishing
      these 2 injury types in clinical practice as different open-globe injuries.

PMID- 24030538
TI  - Non-contact lens use-related Acanthamoeba keratitis in southern Turkey:
      evaluation of risk factors and clinical features.
AB  - PURPOSE: To assess the diagnostic methods, risk factors, and clinical features of
      Acanthamoeba keratitis cases in patients who do not wear contact lenses. METHODS:
      Medical records of 26 consecutive patients with non-contact lens-related
      Acanthamoeba keratitis, who were followed up at the tertiary eye care center
      between May 2010 and May 2012, were analyzed. Laboratory, demographic, and
      clinical findings were evaluated pertaining to the patients. RESULTS: Twenty-six
      non-contact lens-related Acanthamoeba keratitis cases were included in the study.
      The main risk factors were trauma (group 1, n = 13 patients) and ocular surface
      disease (group 2, n = 12 patients). One patient had both of the risk factors
      mentioned above. Overall test results showed that Acanthamoeba positivity rates
      were 15.3% for direct microscopy, 46.1% for culture, 92.3% for conventional
      polymerase chain reaction (PCR), and 100% for real-time PCR. The rates of full
      thickness corneal involvement and ring-shaped infiltrations were higher in group
      2, whereas superficial keratitis and radial keratoneuritis were higher in group
      1. The final visual acuities were significantly better in group 1 than group 2
      (p<0.025). CONCLUSIONS: This study is the first regional report from Turkey about
      Acanthamoeba keratitis in non-contact lens users. A majority of cases admitted to
      a tertiary eye care center were related to trauma or ocular surface disease.
      Physician suspicion is critically important for the timely diagnosis of these
      cases. At this point, molecular diagnostic tests (PCR or real-time PCR) seem to
      support the clinical diagnosis of Acanthamoeba keratitis with the help of fast
      and reliable results.

PMID- 24030539
TI  - Cytomegalovirus retinitis in patients with AIDS before and after introduction of
      HAART in China.
AB  - PURPOSE: To determine the prevalence of cytomegalovirus retinitis (CMVR) and
      other fundus lesions in subjects with acquired immunodeficiency syndrome (AIDS)
      before and after the introduction of highly active antiretroviral therapy (HAART)
      in China. METHODS: The retrospective study included subjects with AIDS who
      consecutively attended a third referral center in Beijing before and after HAART
      was introduced. Comprehensive systemic and ophthalmic examinations, including
      CD4+ T-cell count, ophthalmoscopy, and fundus photography, were carried out.
      RESULTS: A total of 173 HIV-infected, HAART-naive individuals and 267 people
      undergoing HAART were included in the study. The HAART-naive group as compared
      with the HAART group was significantly older (39.5 +/- 11.5 years versus 36.7 +/-
      11.2 years; p = 0.02) and included significantly more men (p = 0.045). Prevalence
      of CMVR, microvascular retinopathy, and optic neuropathy in the HAART group (9.0
      +/- 1.8%, 7.9 +/- 1.7%, and 4.9 +/- 1.3%, respectively) were significantly (all
      p<=0.001) lower than in the HAART-naive group (20.2 +/- 3.1%, 31.2 +/- 3.5%, and
      13.9 +/- 2.6%, respectively). Microvascular retinopathy was significantly
      associated with HAART-naive status (p<0.001; odds ratio [OR] 0.20; 95% confidence
      interval [CI] 0.12, 0.36) and higher age (p = 0.002; OR 1.04; 95% CI 1.10, 1.06).
      Cytomegalovirus retinitis was significantly associated with CD4+ cell count <50
      cells/MUL (p = 0.001; OR 5.50; 95% CI 1.95, 15.5), HAART-naive status (p = 0.02;
      OR 0.23; 95% CI 0.07, 0.79), and lower best-corrected visual acuity (p<0.001; OR
      5.44; 95% CI 2.11, 14.0). CONCLUSIONS: As in Western countries, prevalence of
      CMVR and microvascular retinopathy in Chinese subjects with AIDS were
      significantly associated with a low CD4+ cell count and a HAART-naive status as
      the 2 major risk factors.

PMID- 24030540
TI  - SD-OCT stages of progression of type 2 macular telangiectasia in a patient
      followed for 3 years.
AB  - PURPOSE: To describe the natural course of type 2 idiopathic macular
      telangiectasia (MT) using spectral-domain optical coherence tomography (SD-OCT).
      METHODS: Analysis of the different stages of progression of type 2 MT during a
      period of 3 years using multimodal imaging, including SD-OCT correlated with
      angiographic and autofluorescence images. The analysis of the different steps was
      obtained initially from the first eye, then successively from the fellow eye when
      progressive changes appeared. RESULTS: The earliest visible alteration at SD-OCT
      was the interruption of the interface between inner segment and ellipsoid (IS/EL)
      (stage 1). The second stage was characterized by the complete interruption of
      both IS/EL interface and external limiting membrane (stage 2). At the next step,
      a wide disruption of the outer nuclear layer was noted (stage 3). The fourth
      stage showed a complete disorganization of the inner layers with aspect of fusion
      of the inner retinal layers associated with progressive atrophy of the outer
      layers (stage 4). Hyper-reflective deposits were found in both the internal and
      external retinal layers (stage 5). Small intraretinal cystoid spaces appeared in
      the different retinal layers (stage 6). This last feature was an earlier
      manifestation of the typical intraretinal cysts that are the well-known OCT
      appearance of type 2 MT. CONCLUSIONS: We describe the 6 steps of progression from
      earlier SD-OCT findings that led to a complete disorganization and fusion of the
      inner layers (probably due to changes in the Muller cells) to the typical
      intraretinal cysts.

PMID- 24030541
TI  - Is the effect of intravitreal triamcinolone acetonide on diabetic macular edema
      dose-dependent?
AB  - PURPOSE: To determine whether the effect of intravitreal triamcinolone acetonide
      in diffuse diabetic macular edema is dose-dependent regarding the velocity and
      duration of macular edema reduction, visual acuity improvement, and induction of
      predictable complications. METHODS: This clinical prospective study included 32
      consecutive patients (32 eyes) with diffuse diabetic macular edema. All patients
      had visual acuity, fluorescein angiogram, and optical coherence tomography
      performed at the initial visit (baseline). Single triamcinolone acetonide
      injection was applied intravitreally in different high doses using sterile
      technique followed by timolol-maleate 0.5%/acetazolamide fixed combination
      eyedrops twice a day for 6 consecutive months. Macular edema, intraocular
      pressure, and best-corrected distance visual acuity were reviewed after 5 days
      and 1, 3, and 6 months. RESULTS: Intraocular pressure did not change
      significantly during 6 months and was maintained within normal levels in all
      patients using prescribed antiglaucoma therapy. Best-corrected distance visual
      acuity and macular edema were better than preoperatively even 6 months after
      treatment while the highest improvement was recorded 1 month after treatment.
      There was a slight correlation of macular edema reduction and triamcinolone dose,
      especially in central 1-mm diameter zone 6 months post triamcinolone acetonide
      intravitreal injection, but it was not statistically significant. CONCLUSIONS:
      Triamcinolone intravitreal injection is a relatively safe, inexpensive, and
      effective method used for diabetic macular edema reduction but its effect is not
      proven to be dose-dependent, at least in 10-32 mg dose range. Macular edema
      reduction rate correlated significantly with preoperative edema.

PMID- 24030542
TI  - Descemet stripping automated endothelial keratoplasty after 2 previously rejected
      femtosecond laser-assisted keratoplasties.
AB  - PURPOSE: To report on a patient with a welding flash burn with subsequent
      scarring and edema who twice underwent femtosecond laser-assisted keratoplasty
      (FLAK). Both grafts failed due to endothelial decompensation. He subsequently
      underwent successful Descemet stripping automated endothelial keratoplasty
      (DSAEK) under the second FLAK graft to decrease rejection risk and prevent
      further full-thickness keratoplasty. METHODS: A 51-year-old man with a history of
      2 FLAK procedures with subsequent graft failures likely from noncompliance with
      postoperative medications had diffuse microcystic edema with a visual acuity of
      counting fingers at 5 feet. The patient underwent DSAEK procedure 4 months after
      the second FLAK procedure. RESULTS: No dehiscence occurred during second laser
      trephination of cornea. Sections of mild misalignment between the first and
      second FLAK graft trephinations were noted on optical coherence tomography. Post
      DSAEK, the patient had a rapidly clearing, well-attached graft with mild temporal
      overlap of the graft-host interface. All sutures were removed from the overlying
      FLAK graft by 3 months after DSAEK (7 months after repeat FLAK). At 9 months post
      DSAEK, the patient's uncorrected visual acuity was 20/40 and best spectacle
      corrected visual acuity was 20/30. CONCLUSIONS: Early secondary femtosecond laser
      trephination after first FLAK is possible even if the second graft is misaligned.
      A crescent remnant of the original graft was well-healed into the host cornea 7.5
      months after the original surgery. The 3-month-old second FLAK graft was able to
      support a DSAEK surgery and rapid postoperative visual recovery. All sutures were
      removed from the cornea by 7 months after the second FLAK surgery.

PMID- 24030543
TI  - Large magnetoresistance and charge transfer between the conduction and magnetic
      electrons in layered oxyselenide BiOCu(0.96)Se.
AB  - The electrical and magnetic properties of slightly Cu-deficient BiOCu(0.96)Se
      have been investigated using neutron and X-ray diffraction, ac magnetic
      susceptibility, magnetization and electric resistivity measurements. The layered
      BiOCu(0.96)Se crystallizes into a tetragonal lattice with a P4/nmm symmetry.
      Thermal profiles of the electrical resistivity reveal a semiconductor type
      behavior, but depart from its course at low temperatures when antiferromagnetic
      coupling becomes thermally loosened at 140 K. Positive magnetoresistances are
      obtained at all temperatures studied. With an applied magnetic field of 0.5 kOe,
      the magnetoresistance reaches 235% at 2 K. It decreases with increasing
      temperature, but stabilizes to 70% above 60 K. Both ferromagnetic and
      antiferromagnetic coupling are detected between the Cu spins in the SeCu4
      pyramidal blocks, which results in a non-collinear spin arrangement at low
      temperatures. The antiferromagnetic component becomes disordered above T(N) = 140
      K, whereas the ferromagnetic moment persists up to T(C) = 300 K. Interlayer
      charge transfer between the conduction and magnetic electrons gives rise to an
      anomaly in the magnetic order parameter.

PMID- 24030544
TI  - Efficient photocatalytic hydrogen production in water using a cobalt(III)
      tetraaza-macrocyclic catalyst: electrochemical generation of the low-valent Co(I)
      species and its reactivity toward proton reduction.
AB  - A very efficient homogeneous system for visible-light driven hydrogen production
      in water is reported. This comprises the [Co(CR)Cl2](+) cobalt(III) tetraaza
      macrocyclic complex (Cat1) as a noble metal-free catalyst, [Ru(bpy)3]Cl2 as a
      photosensitizer and ascorbate/ascorbic acid as a sacrificial electron donor and
      buffer. This system gives up to 1000 turnovers at pH 4.0 versus the catalyst with
      a relatively low photosensitizer/catalyst ratio (10/1) and a high concentration
      of catalyst (1 * 10(-4) M), thus producing a significant amount of H2 (12.3 mL
      for 5 mL of solution). It also exhibits long-term stability (more than 20 hours).
      The efficiency of Cat1 has been compared under the same experimental conditions
      to those of three other H2-evolving catalysts, which are known to operate in
      water, [Co{(DO)(DOH)pn}Br2] (Cat2), [Co(dmbpy)3]Cl2 (Cat3) and [Rh(dmbpy)2Cl2]Cl
      (Cat4). These comparative studies show that Cat4, although based on a noble
      metal, is about four times less active, while Cat2 and Cat3 produce more than one
      hundred times less hydrogen than Cat1. The low-valent CoI form of Cat1 has been
      successfully electrogenerated in CH3CN. Its high stability can be related to the
      high catalytic performance of the Cat1 system. We have also shown that in acidic
      aqueous solution (photocatalytic conditions) reduction at a slightly more
      negative potential than the Co(II)/Co(I) couple is needed to ensure efficient
      catalysis; this reduction is performed by the photogenerated [Ru(II)(bpy)2(bpy(
      ))](+) species.

PMID- 24030545
TI  - Clinical and pharmacokinetic considerations for the use of daptomycin in patients
      with Staphylococcus aureus bacteraemia and severe renal impairment.
AB  - OBJECTIVES: To support daptomycin dosing recommendations in patients with
      Staphylococcus aureus bacteraemia (SAB) and severe renal impairment using
      simulations from a population pharmacokinetic model for daptomycin. METHODS: A
      population pharmacokinetic model was developed using 4875 daptomycin plasma
      concentrations from 442 subjects. Daptomycin 24 h AUC and Cmax were then
      simulated for subjects with a CL(CR) < 30 mL/min [with or without haemodialysis
      (HD) or continuous ambulatory peritoneal dialysis (CAPD)] for different dosing
      frequencies (every 24 h, every 48 h and three times weekly) with doses of 4 mg/kg
      and 6 mg/kg. These results were compared with efficacy and safety exposure
      references based on daily dosing to understand the implications of less frequent
      dosing (for example, higher exposures on day 1 versus day 2) and to evaluate the
      4 mg/kg versus 6 mg/kg regimens. RESULTS: Substantially more patients with SAB
      and severe renal impairment were underexposed (24 h AUCs compared with an
      efficacy reference of 6 mg/kg/day, CLCR >= 30 mL/min, pivotal trial population)
      at 4 mg/kg every 48 h compared with 6 mg/kg. Cmax results also favoured 6 mg/kg
      every 48 h over 4 mg/kg every 48 h. Both exposure metrics at 6 mg/kg every 48 h
      also stayed below the defined safety limits (based on 12 mg/kg/day, CL(CR) >80
      mL/min, the highest dose in controlled clinical trials). CONCLUSIONS: For
      patients with SAB and CLCR <30 mL/min, or receiving HD or CAPD, the dose
      recommendation of 6 mg/kg every 48 h provides appropriate daptomycin exposure for
      this indication; this will not be the case for patients receiving 4 mg/kg every
      48 h.

PMID- 24030546
TI  - Initiatives to improve appropriate antibiotic prescribing in primary care.
AB  - Influencing clinicians' prescribing behaviour is important because inappropriate
      use and overuse of antibiotics are major drivers of antibiotic resistance. A
      systematic review of interventions for promoting prudent prescribing of
      antibiotics by general practitioners suggests that multifaceted interventions
      will maximize acceptability. This article reports how this type of approach has
      been used successfully in Derbyshire, UK over the last 4 years. The range of
      interventions that have been used includes educational meetings (both open group
      events and others targeted at higher prescribers in the surgery) using a
      supportive and guiding ethos; the provision of support materials aimed at
      empowering avoidance or delayed antibiotic prescribing, where appropriate, and
      improving patients' knowledge and confidence in self-management; and the
      production of different treatment guidelines incorporating key messages with
      evidence, indicating where antibiotics are unlikely to be of benefit. Education
      on antibiotics in schools was a novel approach, which was developed in North
      Derbyshire to increase public awareness of the appropriate treatment for common
      illnesses without using antibiotics. 

PMID- 24030548
TI  - Controlled display of enzyme activity with a stretchable hydrogel.
AB  - An enzyme-incorporated hydrogel made of alginate and polyacrylamide shows a
      linearly increased activity with the enlargement of surface area upon stretching.

PMID- 24030549
TI  - Serum endostatin and risk of mortality in the elderly: findings from 2 community
      based cohorts.
AB  - OBJECTIVE: Experimental data imply that endostatin, a proteolytically cleaved
      fragment of collagen XVIII, could be involved in the development of
      cardiovascular disease and cancer. Prospective data concerning the relation
      between circulating endostatin and mortality are lacking. Accordingly, we aimed
      to study associations between circulating endostatin and mortality risk. APPROACH
      AND RESULTS: Serum endostatin was analyzed in 2 community-based cohorts: the
      Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women
      50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala
      Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow
      up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person
      years at risk), and 417 participants died in ULSAM (6.7/100 person-years at
      risk). In multivariable Cox regression models adjusted for age and established
      cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was
      associated with a hazard ratio of mortality of 1.39 and 95% confidence interval,
      1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin
      was also associated with cardiovascular mortality (177 deaths; hazard ratio per
      SD of ln[endostatin] 1.45, 95% confidence interval [1.25-1.71]) and cancer
      mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence
      interval [1.10-1.66]). CONCLUSIONS: High serum endostatin was associated with
      increased mortality risk in 2 independent community-based cohorts of the elderly.
      Our observational data support the importance of extracellular matrix remodeling
      in the underlying pathophysiology of cardiovascular disease and cancer.

PMID- 24030550
TI  - Carotid atherosclerosis and incident atrial fibrillation.
AB  - OBJECTIVE: Atrial fibrillation (AF) and atherosclerotic vascular disease are
      closely entangled disorders and often coexist. Whether atherosclerosis
      predisposes to the development of AF has not been fully elucidated. APPROACH AND
      RESULTS: This study was performed within the framework of the Bruneck Study, a
      population-based survey with near-complete participation (932 of 1000), long-term
      follow-up (1990-2010), and thorough assessment of AF. The carotid arteries served
      as a window to systemic atherosclerosis and were scanned every 5 years. Pooled
      logistic regression and multistate proportional hazards models were used to
      identify risk predictors of incident AF and effects of AF on mortality. During
      follow-up, 118 new cases of AF were detected (incidence per 1000 person-years of
      8.1; 95% confidence interval, 6.8-9.6). Individuals with atherosclerosis were
      more likely to develop AF than individuals without (odds ratio, 1.8; 95%
      confidence interval, 1.1-3.1; P=0.021). This finding applied to women and men and
      to both baseline and incident atherosclerosis during follow-up. Subjects with
      atherosclerosis and AF were significantly more likely to die than those with
      either condition alone (P=0.0034), and mortality in this group was ~ 4-fold
      compared with individuals free of atherosclerosis and AF (hazard ratio, 4.2; 95%
      confidence interval, 2.6-6.8; P<0.0001). CONCLUSIONS: We found that subjects with
      carotid atherosclerosis are at high risk of developing AF.

PMID- 24030547
TI  - LIS1 controls mitosis and mitotic spindle organization via the LIS1-NDEL1-dynein
      complex.
AB  - Heterozygous LIS1 mutations are responsible for the human neuronal migration
      disorder lissencephaly. Mitotic functions of LIS1 have been suggested from many
      organisms throughout evolution. However, the cellular functions of LIS1 at
      distinct intracellular compartments such as the centrosome and the cell cortex
      have not been well defined especially during mitotic cell division. Here, we used
      detailed cellular approaches and time-lapse live cell imaging of mitosis from
      Lis1 mutant mouse embryonic fibroblasts to reveal critical roles of LIS1 in
      mitotic spindle regulation. We found that LIS1 is required for the tight control
      of chromosome congression and segregation to dictate kinetochore-microtubule (MT)
      interactions and anaphase progression. In addition, LIS1 is essential for the
      establishment of mitotic spindle pole integrity by maintaining normal centrosome
      number. Moreover, LIS1 plays crucial roles in mitotic spindle orientation by
      increasing the density of astral MT plus-end movements toward the cell cortex,
      which enhances cortical targeting of LIS1-dynein complex. Overexpression of NDEL1
      dynein and MT stabilization rescues spindle orientation defects in Lis1 mutants,
      demonstrating that mouse LIS1 acts via the LIS1-NDEL1-dynein complex to regulate
      astral MT plus-ends dynamics and establish proper contacts of MTs with the cell
      cortex to ensure precise cell division.

PMID- 24030551
TI  - Apolipoprotein A-IV expression in mouse liver enhances triglyceride secretion and
      reduces hepatic lipid content by promoting very low density lipoprotein particle
      expansion.
AB  - OBJECTIVE: Previous studies demonstrated that apolipoprotein A-IV (apoA-IV)
      promotes apoB lipoprotein-mediated triglyceride (TG) secretion in transfected
      enterocytes and hepatoma cells; however, evidence for a role in lipid transport
      in vivo is lacking. Using mouse models, we explored the role of apoA-IV in
      hepatic very low density lipoprotein-mediated lipid efflux under conditions that
      promote hepatic steatosis. APPROACH AND RESULTS: Hepatic steatosis, induced by
      either high-fat diet or enhanced de novo lipogenesis caused by transgenic
      overexpression of SREBP-1a (SREBP-1a(Tg)), was associated with up to a 43-fold
      induction of hepatic apoA-IV mRNA and protein levels. In both models, a positive
      linear correlation between hepatic TG content and apoA-IV mRNA abundance was
      observed (r(2)=0.8965). To examine whether induction of apoA-IV affected hepatic
      TG secretion, SREBP-1a(Tg) mice were crossed with Apoa4 knockout mice. With
      Triton blockade of peripheral lipolysis, SREBP-1a(Tg)/Apoa4 knockout mice
      demonstrated a 24% reduction in hepatic TG secretion rate, relative to SREBP
      1a(Tg) controls, but no change in apoB production. Negative stain electron
      microscopy revealed a 33% decrease in the abundance of secreted very low density
      lipoprotein particles with diameters >= 120 nm. Conversely, mice infected with a
      recombinant human apoA-IV adenovirus demonstrated a 52% increase in the hepatic
      TG secretion rate, relative to controls, a 38% reduction in liver TG content, and
      a 43% increase in large diameter (>= 120 nm) very low density lipoprotein
      particles, with no change in apoB secretion. CONCLUSIONS: Hepatic steatosis in
      mice induces hepatic apoA-IV expression, which in turn promotes lipoprotein
      particle expansion and reduces hepatic lipid burden without increasing the number
      of secreted atherogenic apoB-containing lipoprotein particles.

PMID- 24030552
TI  - Meiotic recombination strongly influences GC-content evolution in short regions
      in the mouse genome.
AB  - Meiotic recombination is known to influence GC-content evolution in large regions
      of mammalian genomes by favoring the fixation of G and C alleles and increasing
      the rate of A/T to G/C substitutions. This process is known as GC-biased gene
      conversion (gBGC). Until recently, genome-wide measures of fine-scale
      recombination activity were unavailable in mice. Additionally, comparative
      studies focusing on mouse were limited as the closest organism with its genome
      fully sequenced was rat. Here, we make use of the recent mapping of double strand
      breaks (DSBs), the first step of meiotic recombination, in the mouse genome and
      of the sequencing of mouse closely related subspecies to analyze the fine-scale
      evolutionary signature of meiotic recombination on GC-content evolution in
      recombination hotspots, short regions that undergo extreme rates of
      recombination. We measure substitution rates around DSB hotspots and observe that
      gBGC is affecting a very short region (~ 1 kbp) in length around these hotspots.
      Furthermore, we can infer that the locations of hotspots evolved rapidly during
      mouse evolution.

PMID- 24030554
TI  - From beta- to alpha-proteobacteria: the origin and evolution of rhizobial
      nodulation genes nodIJ.
AB  - Although many alpha- and some beta-proteobacterial species are symbiotic with
      legumes, the evolutionary origin of nitrogen-fixing nodulation remains unclear.
      We examined alpha- and beta-proteobacteria whose genomes were sequenced using
      large-scale phylogenetic profiling and revealed the evolutionary origin of two
      nodulation genes. These genes, nodI and nodJ (nodIJ), play key roles in the
      secretion of Nod factors, which are recognized by legumes during nodulation. We
      found that only the nodulating beta-proteobacteria, including the novel strains
      isolated in this study, possess both nodIJ and their paralogous genes (DRA
      ATPase/permease genes). Contrary to the widely accepted scenario of the alpha
      proteobacterial origin of rhizobia, our exhaustive phylogenetic analysis showed
      that the entire nodIJ clade is included in the clade of Burkholderiaceae DRA
      ATPase/permease genes, that is, the nodIJ genes originated from gene duplication
      in a lineage of the beta-proteobacterial family. After duplication, the
      evolutionary rates of nodIJ were significantly accelerated relative to those of
      homologous genes, which is consistent with their novel function in nodulation.
      The likelihood analyses suggest that this accelerated evolution is not associated
      with changes in either nonsynonymous/synonymous substitution rates or
      transition/transversion rates, but rather, in the GC content. Although the low GC
      content of the nodulation genes has been assumed to reflect past horizontal
      transfer events from donor rhizobial genomes with low GC content, no rhizobial
      genome with such low GC content has yet been found. Our results encourage a
      reconsideration of the origin of nodulation and suggest new perspectives on the
      role of the GC content of bacterial genes in functional adaptation. 

PMID- 24030553
TI  - The evolution of microRNA pathway protein components in Cnidaria.
AB  - In the last decade, it became evident that posttranscriptional regulation of gene
      expression by microRNAs is a central biological process in both plants and
      animals. Yet, our knowledge about microRNA biogenesis and utilization in animals
      stems mostly from the study of Bilateria. In this study, we identified genes
      encoding the protein components of different parts of the microRNA pathway in
      Cnidaria, the likely sister phylum of Bilateria. These genes originated from
      three cnidarian lineages (sea anemones, stony corals, and hydras) that are
      separated by at least 500 My from one another. We studied the expression and
      phylogeny of the cnidarian homologs of Drosha and Pasha (DGCR8) that compose the
      microprocessor, the RNAse III enzyme Dicer and its partners, the HEN1
      methyltransferase, the Argonaute protein effectors, as well as members of the
      GW182 protein family. We further reveal that whereas the bilaterian dicer
      partners Loquacious/TRBP and PACT are absent from Cnidaria, this phylum contains
      homologs of the double-stranded RNA-binding protein HYL1, the Dicer partner found
      in plants. We also identified HYL1 homologs in a sponge and a ctenophore. This
      finding raises questions regarding the independent evolution of the microRNA
      pathway in plants and animals, and together with the other results shed new light
      on the evolution of an important regulatory pathway. 

PMID- 24030555
TI  - Discordance of species trees with their most likely gene trees: a unifying
      principle.
AB  - A labeled gene tree topology that disagrees with a labeled species tree topology
      is said to be anomalous if it is more probable under a coalescent model for gene
      lineage evolution than the labeled gene tree topology that matches the species
      tree. It has previously been shown that as a consequence of short internal
      branches of the species tree, for every labeled species tree topology with five
      or more taxa, and for asymmetric four-taxon species tree topologies, an
      assignment of species tree branch lengths can be made which gives rise to
      anomalous gene trees (AGTs). Here, I offer an alternative characterization of
      this result--a labeled species tree topology produces AGTs if and only if it
      contains two consecutive internal branches in an ancestor-descendant relationship
      -and I provide a proof that follows from the change in perspective. The
      reformulation and alternative proof of the existence result for AGTs provide the
      insight that it is not merely short internal branches that generate AGTs, but
      instead, short internal branches that are arranged consecutively.

PMID- 24030556
TI  - Influence of acrylamide monomer addition to the acrylic denture-base resins on
      mechanical and physical properties.
AB  - The aim of the study was to evaluate the effect of adding acrylamide monomer
      (AAm) on the characterization, flexural strength, flexural modulus and thermal
      degradation temperature of poly(methyl methacrylate) (PMMA) denture-base resins.
      Specimens (n=10) were fabricated from a conventional heat-activated QC-20 (Qc-)
      and a microwave heat-activated Acron MC (Ac-) PMMA resins. Powder/liquid ratio
      followed the manufacturer's instructions for the control groups (Qc-c and Ac-c)
      and for the copolymer groups, the resins were prepared with 5% (-5), 10% (-10),
      15% (-15) and 20% (-20) acrylamide contents, according to the molecular weight
      ratio, respectively. The flexural strength and flexural modulus were measured by
      a three-point bending test. The data obtained were statistically analyzed by
      Kruskal-Wallis test (alpha=0.05) to determine significant differences between the
      groups. The chemical structures of the resins were characterized by the nuclear
      magnetic resonance spectroscopy. Thermal stabilities were determined by
      thermogravimetric analysis (TGA) with a heating rate of 10  degrees C?min(-1)
      from 35  degrees C to 600  degrees C. Control groups from both acrylic resins
      showed the lowest flexural strength values. Qc-15 showed significant increase in
      the flexural strength when compared to Qc-c (P<0.01). Ac-10 and Ac-15 showed
      significance when compared to Ac-c (P<0.01). Acrylamide incorporation increased
      the elastic modulus in Qc-10, Qc-15 and Qc-20 when compared to Qc-c (P<0.01).
      Also significant increase was observed in Ac-10, Ac-15 and Ac-20 copolymer groups
      when compared to Ac-c (P<0.01). According to the (1)H-nuclear magnetic resonance
      (NMR) results, acrylamide copolymerization was confirmed in the experimental
      groups. TGA results showed that the thermal stability of PMMA is increased by the
      insertion of AAm. 

PMID- 24030557
TI  - Efficacy of two calcium phosphate pastes on the remineralization of artificial
      caries: a randomized controlled double-blind in situ study.
AB  - To test the efficacy of two calcium phosphate pastes compared to that of fluoride
      toothpaste on remineralizing artificial caries in situ, this study had a double
      blind crossover in situ design, involving three experimental phases of 14 days
      each, with an 8-day washout period between phases. Nine healthy subjects
      participated in the study. The subjects wore removable palatal appliances mounted
      with six human enamel slabs with artificial caries lesions, and in each of the
      experimental phases, used one of the following methods two times/day: group A,
      brushing with 1.0 g of Colgate Regular Flavor, followed by applying 0.25 g of
      Tooth Mousse Plus; group B, brushing with 0.25 g of Clinpro Tooth Creme; and
      group C, brushing with 1.0 g of Colgate Regular Flavor. After 14 days, the enamel
      slabs (54 slabs/group) were embedded in resin, sectioned and examined with a
      polarized-light microscope, and the lesion areas were quantified using Image-Pro
      Plus. All experimental groups showed a significant reduction in lesion area
      compared to the initial lesion area (paired t-test, P<0.001). The mean reduction
      in lesion area of Groups A, B and C were (0.029+/-0.010), (0.030+/-0.009) and
      (0.027+/-0.009) mm(2), respectively. There were no statistical differences
      between groups (Kruskal-Wallis test, P>0.05). All three groups remineralized the
      enamel slab lesions, indicating model sensitivity to fluoride. Given the
      differences in usage amounts and treated regimens, Clinpro Tooth Creme provided
      similar benefits to the fluoride toothpaste; however, no additional benefit of
      Tooth Mousse Plus was observed when used in conjunction with the fluoride
      toothpaste.

PMID- 24030558
TI  - Bariatric surgery in minority patients before and after implementation of a
      centers of excellence program.

PMID- 24030559
TI  - PI3Kgamma kinase activity is required for optimal T-cell activation and
      differentiation.
AB  - Phosphatidylinositol-3-kinase gamma (PI3Kgamma) is a leukocyte-specific lipid
      kinase with signaling function downstream of G protein-coupled receptors to
      regulate cell trafficking, but its role in T cells remains unclear. To
      investigate the requirement of PI3Kgamma kinase activity in T-cell function, we
      studied T cells from PI3Kgamma kinase-dead knock-in (PI3Kgamma(KD/KD)) mice
      expressing the kinase-inactive PI3Kgamma protein. We show that CD4(+) and CD8(+)
      T cells from PI3Kgamma(KD/KD) mice exhibit impaired TCR/CD28-mediated activation
      that could not be rescued by exogenous IL-2. The defects in proliferation and
      cytokine production were also evident in naive and memory T cells. Analysis of
      signaling events in activated PI3Kgamma(KD/KD) T cells revealed a reduction in
      phosphorylation of protein kinase B (AKT) and ERK1/2, a decrease in lipid raft
      formation, and a delay in cell cycle progression. Furthermore, PI3Kgamma(KD/KD)
      CD4(+) T cells displayed compromised differentiation toward Th1, Th2, Th17, and
      induced Treg cells. PI3Kgamma(KD/KD) mice also exhibited an impaired response to
      immunization and a reduced delayed-type hypersensitivity to Ag challenge. These
      findings indicate that PI3Kgamma kinase activity is required for optimal T-cell
      activation and differentiation, as well as for mounting an efficient T cell
      mediated immune response. The results suggest that PI3Kgamma kinase inhibitors
      could be beneficial in reducing the undesirable immune response in autoimmune
      diseases. 

PMID- 24030560
TI  - Blurred vision: targeting a diagnosis.

PMID- 24030562
TI  - What is the future of hospitals?

PMID- 24030561
TI  - Different combined oral contraceptives and the risk of venous thrombosis:
      systematic review and network meta-analysis.
AB  - OBJECTIVE: To provide a comprehensive overview of the risk of venous thrombosis
      in women using different combined oral contraceptives. DESIGN: Systematic review
      and network meta-analysis. DATA SOURCES: PubMed, Embase, Web of Science,
      Cochrane, Cumulative Index to Nursing and Allied Health Literature, Academic
      Search Premier, and ScienceDirect up to 22 April 2013. REVIEW METHODS:
      Observational studies that assessed the effect of combined oral contraceptives on
      venous thrombosis in healthy women. The primary outcome of interest was a fatal
      or non-fatal first event of venous thrombosis with the main focus on deep venous
      thrombosis or pulmonary embolism. Publications with at least 10 events in total
      were eligible. The network meta-analysis was performed using an extension of
      frequentist random effects models for mixed multiple treatment comparisons.
      Unadjusted relative risks with 95% confidence intervals were reported. The
      requirement for crude numbers did not allow adjustment for potential confounding
      variables. RESULTS: 3110 publications were retrieved through a search strategy;
      25 publications reporting on 26 studies were included. Incidence of venous
      thrombosis in non-users from two included cohorts was 1.9 and 3.7 per 10,000
      woman years, in line with previously reported incidences of 1-6 per 10,000 woman
      years. Use of combined oral contraceptives increased the risk of venous
      thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9
      to 4.3). The relative risk of venous thrombosis for combined oral contraceptives
      with 30-35 ug ethinylestradiol and gestodene, desogestrel, cyproterone acetate,
      or drospirenone were similar and about 50-80% higher than for combined oral
      contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was
      observed for gestodene, desogestrel, and levonorgestrel, with higher doses being
      associated with higher thrombosis risk. CONCLUSION: All combined oral
      contraceptives investigated in this analysis were associated with an increased
      risk of venous thrombosis. The effect size depended both on the progestogen used
      and the dose of ethinylestradiol.

PMID- 24030563
TI  - Hospitals without walls.

PMID- 24030564
TI  - Abolishing purchaser-provider split helped New Zealand scheme to cut costs, says
      King's Fund.

PMID- 24030565
TI  - College calls for major overhaul of the delivery of care.

PMID- 24030566
TI  - From testing the champions to championing the locals.

PMID- 24030567
TI  - Cancer care in the US needs a radical overhaul, says Institute of Medicine.

PMID- 24030568
TI  - Feeling small: exploring the tactile perception limits.
AB  - The human finger is exquisitely sensitive in perceiving different materials, but
      the question remains as to what length scales are capable of being distinguished
      in active touch. We combine material science with psychophysics to manufacture
      and haptically explore a series of topographically patterned surfaces of
      controlled wavelength, but identical chemistry. Strain-induced surface wrinkling
      and subsequent templating produced 16 surfaces with wrinkle wavelengths ranging
      from 300 nm to 90 MUm and amplitudes between 7 nm and 4.5 MUm. Perceived
      similarities of these surfaces (and two blanks) were pairwise scaled by
      participants, and interdistances among all stimuli were determined by individual
      differences scaling (INDSCAL). The tactile space thus generated and its two
      perceptual dimensions were directly linked to surface physical properties - the
      finger friction coefficient and the wrinkle wavelength. Finally, the lowest
      amplitude of the wrinkles so distinguished was approximately 10 nm, demonstrating
      that human tactile discrimination extends to the nanoscale.

PMID- 24030570
TI  - A benzothiadiazole end capped donor-acceptor based small molecule for organic
      electronics.
AB  - A benzothiadiazole end-capped small molecule 3,6-bis(5-(benzo
      [c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)-2,5-bis(2-butyloctyl)pyrrolo-[3,4
      c]pyrrole-1,4(2H,5H)-dione (BO-DPP-BTZ) using a fused aromatic moiety DPP (at the
      centre) is designed and synthesized. BO-DPP-BTZ is a donor-acceptor-donor (D-A-D)
      structure which possesses a band gap of 1.6 eV and exhibits a strong solid state
      ordering inferred from ~120 nm red shift of the absorption maxima from solution
      to thin film. Field-effect transistors utilizing a spin coated thin film of BO
      DPP-BTZ as an active layer exhibited a hole mobility of 0.06 cm(2) V(-1) s(-1).
      Solution-processed bulk heterojunction organic photovoltaics employing a blend of
      BO-DPP-BTZ and [70]PCBM demonstrated a power conversion efficiency of 0.9%.

PMID- 24030569
TI  - Genetic variation at 8q24, family history of cancer, and upper gastrointestinal
      cancers in a Chinese population.
AB  - Genetic variation at 8q24 is associated with prostate, bladder, breast,
      colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a
      role for variation at 8q24 in familial clustering of upper gastrointestinal
      cancers has not been studied. In order to explore potential inherited
      susceptibility, we analyzed epidemiologic data from a population-based case
      control study of upper gastrointestinal cancers from Taixing, China. The study
      population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and
      415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and
      these cancers were stratified by family history of cancer. Odds ratios and 95%
      confidence intervals were adjusted for potential confounders: age, sex,
      education, tobacco smoking, alcohol consumption, and BMI at interview. We also
      adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori
      (stomach cancer). In a dominant model, among those with a family history of
      cancer, rs1447295 was positively associated with liver cancer (OR(adj) 2.80; 95%
      CI 1.15-6.80). Heterogeneity was observed (P(heterogeneity) = 0.029) with
      rs6983267 and liver cancer, with positive association in the dominant model among
      those with a family history of cancer and positive association in the recessive
      model among those without a family history of cancer. When considered in a
      genetic risk score model, each additional 8q24 risk genotype increased the odds
      of liver cancer by two-fold among those with a family history of cancer (OR(adj)
      2.00; 95% CI 1.15-3.47). These findings suggest that inherited susceptibility to
      liver cancer may exist in the Taixing population and that variation at 8q24 might
      be a genetic component of that inherited susceptibility.

PMID- 24030571
TI  - Bioequivalence of canakinumab liquid pre-filled syringe and reconstituted
      lyophilized formulations following 150 mg subcutaneous administration: a
      randomized study in healthy subjects.
AB  - BACKGROUND: Canakinumab is a human anti-interleukin-1beta antibody approved for
      the treatment of cryopyrin associated periodic syndrome currently formulated as a
      lyophilized powder requiring reconstitution. A new formulation (solution for
      injection as pre-filled syringe) has been developed to avoid reconstitution.
      OBJECTIVE: The objective of this study was to evaluate the bioequivalence of pre
      filled syringe and reconstituted formulations following 150 mg administration in
      healthy subjects. METHODS: This was an open-labeled, randomized, single dose,
      parallel-group study in 130 healthy subjects, followed for 120 days. Subjects
      received a single subcutaneous injection of 150 mg canakinumab after either
      reconstitution or in pre-filled syringe formulation, followed by
      pharmacokinetics/pharmacodynamics evaluations and safety assessments. The main
      outcome measure for the study was the pharmacokinetic bioequivalence of the two
      formulations, which was concluded if the 90% confidence intervals for the ratios
      of AUC(last) (area under the serum concentration-time curve from time zero to
      time of last measurable concentration) and C(max) (maximum serum concentration)
      were entirely contained within the interval, 0.80-1.25. RESULTS: The arithmetic
      mean values for the exposure parameters C(max) and AUC(last) were similar for the
      two formulations. The geometric mean ratio (pre-filled syringe vs. lyophilized
      form) of C(max) and AUC(last) were 0.99 and 1.01. The associated 90% confidence
      intervals were 0.90 to 1.08 and 0.94 to 1.09, respectively. Most common adverse
      events were headache and nasopharyngitis. Neutropenia occurred in 2 cases
      (reported as serious adverse events). No deaths occurred. CONCLUSION: The 150 mg
      liquid pre-filled syringe and lyophilized formulations of canakinumab are
      bioequivalent.

PMID- 24030572
TI  - Risk factors for postoperative wound infections and prolonged hospitalization
      after ventral/incisional hernia repair.
AB  - PURPOSE: The purpose of this study was to identify predictive factors for
      postoperative surgical site infections (SSIs), and increased length of hospital
      stay (LOS) after ventral/incisional hernia repair (VIHR) using multi-center,
      prospectively collected data. STUDY DESIGN: Cases of VIHR from 2009 to 2010 were
      identified in the American College of Surgeons National Surgical Quality
      Improvement Program database. Using logistic regression, a prediction model
      utilizing 41 variables was developed to identify risk factors for postoperative
      SSIs, and increased LOS. Separate analyses were carried out for reducible and
      incarcerated/strangulated cases. RESULTS: A total of 28,269 cases of VIHR were
      identified, 25,172 of which met inclusion criteria. 18,263 cases were reducible
      hernias, and 6,909 cases were incarcerated/strangulated hernias. Our prediction
      model demonstrated that body mass index >=30 kg/m(2), smoking, American Society
      of Anesthesiology (ASA) class 3, open surgical approach, prolonged operative
      times, and inpatient admission following VIHR were significant predictors of
      postoperative SSIs. In addition, risk factors associated with prolonged LOS
      included older age, African American ethnicity, history of alcohol abuse, ASA
      classes 3 and 4, poor functional status, operation within the last 30 days of the
      index operation, history of chronic obstructive pulmonary disease, congestive
      heart failure, and bleeding disorder, as well as open surgical approach, non
      involvement of residents, prolonged operative times, recurrent hernia, emergency
      operation, and low preoperative serum albumin level. CONCLUSIONS: Obesity and
      smoking are modifiable risk factors for SSIs after VIHR, whereas a low serum
      albumin level is a modifiable risk factor for prolonged LOS. Addressing factors
      preoperatively might improve patient outcome, and reduce health care expenditures
      associated with VIHR. In addition, if feasible, the laparoscopic approach should
      be strongly considered.

PMID- 24030574
TI  - Flexible electrofluorochromic devices with the highest contrast ratio based on
      aggregation-enhanced emission (AEE)-active cyanotriphenylamine-based polymers.
AB  - Flexible electrofluorochromic devices were prepared from two electrochromic and
      AEE-active (AEE: aggregation-enhanced emission) cyanoarylamine-containing high
      performance polymers, exhibiting the highest contrast ratio (If/If0) of 151.9 at
      a low working potential. 

PMID- 24030575
TI  - Foreword: European Hip Society Symposium on Management of the Young arthritic
      hip.

PMID- 24030573
TI  - A novel intervention using interactive technology and personal narratives to
      reduce cancer disparities: African American breast cancer survivor stories.
AB  - PURPOSE: There has been a paucity of interventions developed for African American
      women to address persistent health disparities between African American and
      Caucasian breast cancer patients. We developed and piloted a technologically
      innovative, culturally targeted, cancer-communication intervention for African
      American breast cancer patients using African American breast cancer survivor
      stories. METHODS: We rated 917 clips from a video library of survivors' stories
      for likability, clarity and length, and emotional impact (scaled responses) and
      categorized each clip by theme (Coping, Support and Relationships, Healthcare
      Experiences, Follow-up Care, Quality of Life, and Treatment Side Effects). We
      selected 207 clips told by 35 survivors (32-68 years old; 4-30 years after
      diagnosis), fitting one of 12 story topics, for inclusion in the interactive
      video program loaded onto a touch-screen computer. Videos can be searched by
      storyteller or story topics; stories with the strongest emotional impact were
      displayed first in the video program. RESULTS: We pilot tested the video program
      with ten African American breast cancer survivors (mean age, 54; range 39-68
      years), who, after training, watched videos and then evaluated the stories and
      video-program usability. Survivor stories were found to be "interesting and
      informative," and usability was rated highly. Participants identified with
      storytellers (e.g., they "think a lot like me," "have values like mine") and
      agreed that the stories convinced them to receive recommended surveillance
      mammograms. CONCLUSIONS: This novel, cancer-communication technology using
      survivor stories was very favorably evaluated by breast cancer survivors and is
      now being tested in a randomized controlled clinical trial. IMPLICATIONS FOR
      CANCER SURVIVORS: Breast cancer survivors can draw support and information from a
      variety of sources, including from other breast cancer survivors. We developed
      the survivor stories video program specifically for African American survivors to
      help improve their quality of life and adherence to follow-up care. Breast cancer
      survivors' experiences with treatment and living with cancer make them especially
      credible messengers of cancer information. Our novel, interactive technology is
      being tested in a randomized controlled trial and will be more broadly
      disseminated to reach a wider audience.

PMID- 24030576
TI  - Mechanical causes of osteoarthritis in young adults.
AB  - Femoroacetabular impingement is a very common cause of secondary osteoarthritis
      (OA) in the young adult. It is an important co-factor in the better recognized
      prearthritic deformities such as residual hip dysplasia (RHD), Perthes disease
      and slipped capital femoral epiphysis (SCFE). Another subgroup of patients has
      isolated malrotation of the hip joint and/or reduced femoral head-neck offset
      causing femoroacetabular impingement and chronic hip joint pain. Special clinical
      tests and imaging modalities can identify these patients at an early stage when
      they have little or no OA. The common biomechanical pathway for deformities
      causing chronic femoroacetabular impingement is local damage of the capsular
      labrum complex and the cartilage. Understanding the anatomy, biomechanics and
      pathophysiology of these conditions of the hip joint is a prerequisite for
      planning treatment.  

PMID- 24030577
TI  - Hip dysplasia: Treatment by Ganz osteotomy.

PMID- 24030578
TI  - Femoral osteotomy.

PMID- 24030579
TI  - Wear of historical polyethylenes in hip prostheses. Biomechanical success and a
      biological failure.
AB  - ;Polyethylene wear debris induced osteolysis is a major cause of failure in
      artificial hip joints. Sub micrometre size particles are taken up by macrophages
      which are stimulated to release osteolytic cytokines such as TNFalpha. This leads
      to bone resorption, loosening and failure. In vitro cell culture studies have
      shown particles in the size range 0.1 to 1 micrometre to be at least six times
      more reactive than larger particles. Studies of historically used gamma
      irradiated in air polyethylene show increased wear rate with damaged femoral
      heads and with aged and oxidised polyethylene. The aged and oxidised polyethylene
      also produced a greater percentage of smaller particles leading to increased
      osteolytic potential. Combined tribological and biological simulation models have
      been developed for pre-clinical assessment of osteolytic potential of artificial
      hip joints. 

PMID- 24030580
TI  - Long term outcome of the Charnley hip replacement in the young.

PMID- 24030581
TI  - Alternative bearing couples in total hip replacements: Solutions for young
      patients.
AB  - ;There is now considerable clinical concern about the effect of polyethylene wear
      debris induced osteolysis in long term failure of hip replacements. This paper
      compares the wear of stabilised and crosslinked polyethylene to alternative hard
      on hard bearings. The volumetric wear rates of stabilised and moderately
      crosslinked polyethylene 50 to 35 mm<sup>3</sup>/million cycles were less than
      previously reported for historical gamma irradiated in air polyethylene, but
      still of a level that in the long term could cause osteolysis. The moderately
      crosslinked polyethylene produced less wear than non-crosslinked polyethylene,
      but particles were smaller and more reactive resulting in little change in the
      osteolytic potential. Alumina ceramic on ceramic produced substantially less wear
      and osteolytic potential. Metal on metal also produced less wear than
      polyethylene but the particles adversely influence cell viability. 

PMID- 24030582
TI  - Alumina on alumina total hip arthroplasty in patients under 50 years of age.

PMID- 24030583
TI  - Development of metal/metal hip resurfacing.
AB  - This author's development of metal/metal hip resurfacing began in 1989, with the
      first patient implantation in February 1991. In the first three years a pilot
      study identified optimum fixation as hydroxyapatite coated uncemented cups and
      cemented femoral components. From March 1994 hybrid fixed components have been
      used. These implants have generally been satisfactory with respect to fixation
      but high wear of the bearing, metallosis and osteolysis have been seen with some
      components inserted during 1996, a period during which the metal microstructure
      was altered by the heat processes, hot isostatic pressing and solution heat
      treatment. The Birmingham Hip Resurfacing was developed taking account of
      experience with earlier resurfacing designs. This implant employs hybrid fixation
      with a porous ingrowth acetabular component and has an as-cast metal
      microstructure having had no post casting heat treatments. During the past 4
      years the author has performed over 1,000 Birmingham Hip Resurfacingis with a
      total failure rate of less than 1.0%.  

PMID- 24030585
TI  - The effect of doping a molecular spin ladder with non-magnetic impurities.
AB  - Since carrier doping of two-leg spin ladders can theoretically induce a
      superconductive state, investigation of such systems is of great use in the study
      of superconductivity. In this paper, we report the successful creation of a non
      magnetic impurity doped into a two-leg molecular spin ladder and the
      characterization of its magnetic properties. 

PMID- 24030586
TI  - Safety and immunogenicity study of a new purified chick embryo cell rabies
      vaccine Vaxirab-N (Pitman-Moore strain) manufactured in India.
AB  - Zydus Cadila Health care, India developed a new purified chick embryo cell rabies
      vaccine (PCECV, Vaxirab-N; 1 mL) by adapting Pitman-Moore strain of virus on to
      the chick embryo fibroblast cell line in 2006. During 2007-10, a series of safety
      and immunogenicity studies were conducted as per ICH-GCP guidelines after
      obtaining permission from Drug Controller General of India. In the first study,
      Vaxirab-N was administered to 35 healthy adult volunteers by intramuscular (IM)
      route using pre exposure regimen. The geometric mean concentration (GMC) of
      rabies virus neutralizing antibody (RvnAb) of 7.5 IU/mL on day 35. In the second
      study, Vaxirab-N was administered to 35 healthy adult volunteers using simulated
      post- exposure prophylaxis regimen by IM route. A GMC of 6.3 IU/mL on day 14,
      13.2 IU/mL on day 28 and 8.6 IU/mL on day 90 was obtained. In the third study,
      Vaxirab-N administered by intradermal (ID) route using Updated Thai Red Cross
      (TRC) regimen in 36 healthy adult volunteers showed GMC of 7.8 IU/mL on day 14,
      11.5 IU/mL on day 28 and 6.0 IU/mL on day 90. The 4th study was multi centric and
      Vaxirab-N was administered to 129 animal bite cases by IM route using post
      exposure Essen regimen. The GMC following this schedule was 8.2 IU/mL on day 14,
      13.01 IU/mL on day 28, 7.92 IU/mL on day 90 and 3.72 IU/mL on day 180. Mild to
      moderate adverse events were reported to Vaxirab-N but no serious adverse events
      were reported in any of these studies. In conclusion, Vaxirab-N developed by
      Zydus Cadila was found to be safe and immunogenic by both intramuscular and
      intradermal route and is recommended for rabies prophylaxis (CTRI No.
      2010/091/000055 and 2010/091/000509). 

PMID- 24030587
TI  - The time aspect in storing vitrified blastocysts: its impact on survival rate,
      implantation potential and babies born.
AB  - STUDY QUESTION: Does the storage time of vitrified human blastocysts negatively
      impact their survival, the implantation potential of embryos or the malformation
      rate of babies born? SUMMARY ANSWER: There was no evidence that storage times of
      up to 6 years after vitrification (VIT) had a negative impact on blastocyst
      survival, the implantation potential of embryos or the malformation rate of
      babies born. WHAT IS KNOWN ALREADY: Although several thousand children have been
      born after blastocyst VIT, many aspects of this technique remain to be
      elucidated. New applications, such as fertility preservation, lead to long
      storage times of vitrified gametes or embryos but it remains to be determined if
      these vitrified embryos are stable over time. STUDY DESIGN, SIZE, DURATION: A
      retrospective study including 603 transfers was conducted between January 2009
      and April 2012. Blastocysts were vitrified using a closed system.
      PARTICIPANTS/MATERIALS, SETTING, METHODS: All patients underwent the transfer of
      aseptically vitrified/warmed blastocysts in a cryo-cycle. A total of 1077
      blastocysts were transferred. Survival rates (SRs), implantation potential, birth
      rates and characteristics of the children born were evaluated. MAIN RESULTS AND
      THE ROLE OF CHANCE: We found that the storage of vitrified blastocysts in aseptic
      conditions neither impaired blastocyst viability (SR after warming during the
      first year of storage was 83.0% compared with 83.1% after 5-6 years of storage:
      NS) nor decreased pregnancy rates (clinical pregnancy rate after 1 year of
      storage was 40.0 versus 38.5% after 6 years: NS). In addition, no increase in the
      malformation rate over time was observed. LIMITATIONS, REASONS FOR CAUTION: Our
      study only included the transfer of blastocysts which had been vitrified
      aseptically (i.e. using a closed system). Therefore, our results might not be
      applicable to 'open' VIT systems. The long-term follow-up of children born will
      be necessary to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: The
      results suggest that vitrified human blastocysts can be stored for long periods
      of time without significant negative consequences for the offspring. Therefore,
      the method should be of benefit to those patients who need to consider taking
      measures for fertility preservation. STUDY FUNDING/COMPETING INTEREST(S): No
      external funding was sought for this study and the authors have no conflict of
      interest to declare.

PMID- 24030588
TI  - Serotype distribution and antibiotic susceptibility of invasive Streptococcus
      pneumoniae isolates in patients aged 50 years or older in Thailand.
AB  - As the 13-valent pneumococcal conjugate vaccine (PCV13) has been approved for use
      in adults aged 50 y and older, we evaluated vaccine-serotype coverage rate in
      Thai adult patients with invasive pneumococcal infections before the vaccine was
      widely used. Of the 157 S. pneumoniae isolates from normal sterile sites during
      January 2005 to September 2012, 150 (95%) from blood, mean patients' age 69.6
      (range 50-89) years, the overall serotype coverage by PCV13 was 58%. The vaccine
      covered 50%, 56%, 59%, and 68% of the invasive isolates from patients aged 50-59,
      60-69, 70-79, and >=80 y, respectively. The most common vaccine serotypes were 6B
      (17%), 19A (9%), 18C (5%), and 23F (4%). The susceptibility rates of penicillin
      and ceftriaxone were 95% and 96% for nonmeningitis criteria; and 46% and 92% for
      meningitis criteria, respectively. The susceptibilities to other antibiotics
      were: chloramphenicol 76%, clindamycin 80%, erythromycin 57%, levofloxacin 100%,
      ofloxacin 94%, tetracycline 39%, trimethoprim/sulfamethoxazole 37%, linezolid
      99%, and vancomycin 100%, respectively. These data served as a reference for
      monitoring of vaccine serotype coverage with future increased vaccine
      utilization. 

PMID- 24030589
TI  - A rare case of hemolytic anemia in a pediatric patient due to ring dehiscence
      after mitral valve repair: utility of real-time three-dimensional imaging and
      management.
AB  - A rare case of hemolytic anemia in a 3-year-old child due to mitral valve ring
      dehiscence is described. The dehiscence of mitral valve ring was diagnosed
      utilizing real-time three-dimensional echocardiography. The patient subsequently
      underwent reoperation with successful resolution of hemolysis after replacement
      of the ring. 

PMID- 24030590
TI  - Fetal interventions for congenital heart disease in Brazil.
AB  - Fetal interventions have been performed for some congenital heart diseases.
      However, these procedures have not gained wide acceptance due to concerns about
      their efficacy and safety. The aim of this study was to report on a preliminary
      experience with fetal cardiac interventions in Brazil. Twenty-two cardiac
      interventions were performed in 21 fetuses. Thirteen fetuses had critical aortic
      stenosis (CAS), 4 had hypoplastic left heart syndrome (HLHS) and intact
      interatrial septum or small patent foramen ovale, 1 had pulmonary atresia with
      intact ventricular septum (IVS), and 3 had critical pulmonary stenosis (CPS). The
      main outcome variables evaluated were technical success and procedural
      complications as well as pregnancy and postnatal outcomes. Success was achieved
      in 20 of 22 procedures (91%) with 1 failed aortic and 1 failed pulmonary
      valvuloplasties. There was 1 fetal death. No maternal complications occurred. One
      patient with CAS, severe mitral regurgitation, and hydrops died postnatally
      within 5 months of age. All patients with HLHS and restrictive atrial septum died
      after interventional or surgical procedures and prolonged hospitalizations. All
      patients with CPS/IVS survived and achieved a biventricular (BV) circulation
      after neonatal valvuloplasty and ductal stenting. A BV circulation was achieved
      in 4 of 8 patients with CAS and evolving HLHS (one still in utero), including 2
      with initial borderline left ventricles (LV) in whom surgical LV overhaul was
      performed at 9 months of age. In this preliminary experience, the feasibility of
      fetal cardiac interventions and their outcomes were similar to those previously
      reported.

PMID- 24030591
TI  - Autocatalytic cathodic dehalogenation triggered by dissociative electron transfer
      through a C-H...O hydrogen bond.
AB  - A combined action of the C-H...Oalkoxide hydrogen bonding and Cl...pipyrazolyl
      dispersive interactions facilitates intramolecular electron transfer (ET) in the
      transient {Mo(I)(NO)(Tp(Me2))(Oalkoxide)}(-)...HCCl3 adduct ([Tp(Me2)](-) =
      kappa(3)-hydrotris(3,5-dimethylpyrazol-1-yl)borate), setting off a radical
      autocatalytic process, eventually leading to chloroform degradation. In the
      voltammetric curve, this astonishingly fast process is seen as an almost vertical
      drop-down. The potential at which it occurs is favorably shifted by ca. 1 V in
      comparison with uncatalyzed reduction. As predicted by DFT calculations, crucial
      in the initial step is a close and prolonged contact between the electron donor
      (Mo(I) 4d-based SOMO) and acceptor (sigma(*)(C-Cl)-based LUMO). This occurs owing
      to the exceptionally short (dH...O = 1.82 A) and nearly linear C-H...Oalkoxide
      bonding, which is reflected by a large DeltanuC-H red-shift of 380 cm(-1) and a
      noticeable reorganization of electronic density along the H-bond axis. The
      advantageous noncovalent interactions inside the cavity formed by two pyrazolyl
      (pz) rings are strengthened during the C-Cl bond elongation coupled with the ET,
      giving rise to possible transition state stabilization. After the initial period,
      the reaction proceeds as a series of consecutive alternating direct or Mo(II/I)
      mediated electron and proton transfers. Alcohols inhibit the electrocatalysis by
      binding with the {Mo(I)-Oalkoxide}(-) active site, and olefins by trapping
      transient radicals. The proximity and stabilization effects, and competitive
      inhibition in the studied system may be viewed as analogous to those operating in
      enzymatic catalysis.

PMID- 24030592
TI  - Reconstructing an ancestral genotype of two hexachlorocyclohexane-degrading
      Sphingobium species using metagenomic sequence data.
AB  - Over the last 60 years, the use of hexachlorocyclohexane (HCH) as a pesticide has
      resulted in the production of >4 million tons of HCH waste, which has been dumped
      in open sinks across the globe. Here, the combination of the genomes of two
      genetic subspecies (Sphingobium japonicum UT26 and Sphingobium indicum B90A;
      isolated from two discrete geographical locations, Japan and India, respectively)
      capable of degrading HCH, with metagenomic data from an HCH dumpsite (~450 mg HCH
      per g soil), enabled the reconstruction and validation of the last-common
      ancestor (LCA) genotype. Mapping the LCA genotype (3128 genes) to the subspecies
      genomes demonstrated that >20% of the genes in each subspecies were absent in the
      LCA. This includes two enzymes from the 'upper' HCH degradation pathway,
      suggesting that the ancestor was unable to degrade HCH isomers, but descendants
      acquired lin genes by transposon-mediated lateral gene transfer. In addition,
      anthranilate and homogentisate degradation traits were found to be strain
      (selectively retained only by UT26) and environment (absent in the LCA and
      subspecies, but prevalent in the metagenome) specific, respectively. One draft
      secondary chromosome, two near complete plasmids and eight complete lin
      transposons were assembled from the metagenomic DNA. Collectively, these results
      reinforce the elastic nature of the genus Sphingobium, and describe the
      evolutionary acquisition mechanism of a xenobiotic degradation phenotype in
      response to environmental pollution. This also demonstrates for the first time
      the use of metagenomic data in ancestral genotype reconstruction, highlighting
      its potential to provide significant insight into the development of such
      phenotypes. 

PMID- 24030593
TI  - Attributing functions to ectomycorrhizal fungal identities in assemblages for
      nitrogen acquisition under stress.
AB  - Mycorrhizal fungi have a key role in nitrogen (N) cycling, particularly in boreal
      and temperate ecosystems. However, the significance of ectomycorrhizal fungal
      (EMF) diversity for this important ecosystem function is unknown. Here, EMF taxon
      specific N uptake was analyzed via (15)N isotope enrichment in complex root
      associated assemblages and non-mycorrhizal root tips in controlled experiments.
      Specific (15)N enrichment in ectomycorrhizas, which represents the N influx and
      export, as well as the exchange of (15)N with the N pool of the root tip, was
      dependent on the fungal identity. Light or water deprivation revealed
      interspecific response diversity for N uptake. Partial taxon-specific N fluxes
      for ectomycorrhizas were assessed, and the benefits of EMF assemblages for plant
      N nutrition were estimated. We demonstrated that ectomycorrhizal assemblages
      provide advantages for inorganic N uptake compared with non-mycorrhizal roots
      under environmental constraints but not for unstressed plants. These benefits
      were realized via stress activation of distinct EMF taxa, which suggests
      significant functional diversity within EMF assemblages. We developed and
      validated a model that predicts net N flux into the plant based on taxon-specific
      (15)N enrichment in ectomycorrhizal root tips. These results open a new avenue to
      characterize the functional traits of EMF taxa in complex communities. 

PMID- 24030594
TI  - Resistance and resilience of the forest soil microbiome to logging-associated
      compaction.
AB  - Soil compaction is a major disturbance associated with logging, but we lack a
      fundamental understanding of how this affects the soil microbiome. We assessed
      the structural resistance and resilience of the microbiome using a high
      throughput pyrosequencing approach in differently compacted soils at two forest
      sites and correlated these findings with changes in soil physical properties and
      functions. Alterations in soil porosity after compaction strongly limited the air
      and water conductivity. Compaction significantly reduced abundance, increased
      diversity, and persistently altered the structure of the microbiota. Fungi were
      less resistant and resilient than bacteria; clayey soils were less resistant and
      resilient than sandy soils. The strongest effects were observed in soils with
      unfavorable moisture conditions, where air and water conductivities dropped well
      below 10% of their initial value. Maximum impact was observed around 6-12 months
      after compaction, and microbial communities showed resilience in lightly but not
      in severely compacted soils 4 years post disturbance. Bacteria capable of
      anaerobic respiration, including sulfate, sulfur, and metal reducers of the
      Proteobacteria and Firmicutes, were significantly associated with compacted
      soils. Compaction detrimentally affected ectomycorrhizal species, whereas
      saprobic and parasitic fungi proportionally increased in compacted soils.
      Structural shifts in the microbiota were accompanied by significant changes in
      soil processes, resulting in reduced carbon dioxide, and increased methane and
      nitrous oxide emissions from compacted soils. This study demonstrates that
      physical soil disturbance during logging induces profound and long-lasting
      changes in the soil microbiome and associated soil functions, raising awareness
      regarding sustainable management of economically driven logging operations. 

PMID- 24030596
TI  - Rapid genotypic change and plasticity in arbuscular mycorrhizal fungi is caused
      by a host shift and enhanced by segregation.
AB  - Arbuscular mycorrhizal fungi (AMF) are among the most abundant symbionts of
      plants, improving plant productivity and diversity. They are thought to mostly
      grow vegetatively, a trait assumed to limit adaptability. However, AMF can also
      harbor genetically different nuclei (nucleotypes). It has been shown that one AMF
      can produce genotypically novel offspring with proportions of different
      nucleotypes. We hypothesized that (1) AMF respond rapidly to a change of
      environment (plant host) through changes in the frequency of nucleotypes; (2)
      genotypically novel offspring exhibit different genetic responses to
      environmental change than the parent; and (3) genotypically novel offspring
      exhibit a wide range of phenotypic plasticity to a change of environment. We
      subjected AMF parents and offspring to a host shift. We observed rapid and large
      genotypic changes in all AMF lines that were not random. Genotypic and phenotypic
      responses were different among offspring and their parents. Even though growing
      vegetatively, AMF offspring display a broad range of genotypic and phenotypic
      changes in response to host shift. We conclude that AMF have the ability to
      rapidly produce variable progeny, increasing their probability to produce
      offspring with different fitness than their parents and, consequently, their
      potential adaptability to new environmental conditions. Such genotypic and
      phenotypic flexibility could be a fast alternative to sexual reproduction and is
      likely to be a key to the ecological success of AMF. 

PMID- 24030595
TI  - High-fat diet alters gut microbiota physiology in mice.
AB  - The intestinal microbiota is known to regulate host energy homeostasis and can be
      influenced by high-calorie diets. However, changes affecting the ecosystem at the
      functional level are still not well characterized. We measured shifts in cecal
      bacterial communities in mice fed a carbohydrate or high-fat (HF) diet for 12
      weeks at the level of the following: (i) diversity and taxa distribution by high
      throughput 16S ribosomal RNA gene sequencing; (ii) bulk and single-cell chemical
      composition by Fourier-transform infrared- (FT-IR) and Raman micro-spectroscopy
      and (iii) metaproteome and metabolome via high-resolution mass spectrometry. High
      fat diet caused shifts in the diversity of dominant gut bacteria and altered the
      proportion of Ruminococcaceae (decrease) and Rikenellaceae (increase). FT-IR
      spectroscopy revealed that the impact of the diet on cecal chemical fingerprints
      is greater than the impact of microbiota composition. Diet-driven changes in
      biochemical fingerprints of members of the Bacteroidales and Lachnospiraceae were
      also observed at the level of single cells, indicating that there were distinct
      differences in cellular composition of dominant phylotypes under different diets.
      Metaproteome and metabolome analyses based on the occurrence of 1760 bacterial
      proteins and 86 annotated metabolites revealed distinct HF diet-specific
      profiles. Alteration of hormonal and anti-microbial networks, bile acid and
      bilirubin metabolism and shifts towards amino acid and simple sugars metabolism
      were observed. We conclude that a HF diet markedly affects the gut bacterial
      ecosystem at the functional level. 

PMID- 24030597
TI  - Making a living while starving in the dark: metagenomic insights into the energy
      dynamics of a carbonate cave.
AB  - Carbonate caves represent subterranean ecosystems that are largely devoid of
      phototrophic primary production. In semiarid and arid regions, allochthonous
      organic carbon inputs entering caves with vadose-zone drip water are minimal,
      creating highly oligotrophic conditions; however, past research indicates that
      carbonate speleothem surfaces in these caves support diverse, predominantly
      heterotrophic prokaryotic communities. The current study applied a metagenomic
      approach to elucidate the community structure and potential energy dynamics of
      microbial communities, colonizing speleothem surfaces in Kartchner Caverns, a
      carbonate cave in semiarid, southeastern Arizona, USA. Manual inspection of a
      speleothem metagenome revealed a community genetically adapted to low-nutrient
      conditions with indications that a nitrogen-based primary production strategy is
      probable, including contributions from both Archaea and Bacteria. Genes for all
      six known CO2-fixation pathways were detected in the metagenome and RuBisCo genes
      representative of the Calvin-Benson-Bassham cycle were over-represented in
      Kartchner speleothem metagenomes relative to bulk soil, rhizosphere soil and deep
      ocean communities. Intriguingly, quantitative PCR found Archaea to be
      significantly more abundant in the cave communities than in soils above the cave.
      MEtaGenome ANalyzer (MEGAN) analysis of speleothem metagenome sequence reads
      found Thaumarchaeota to be the third most abundant phylum in the community, and
      identified taxonomic associations to this phylum for indicator genes
      representative of multiple CO2-fixation pathways. The results revealed that this
      oligotrophic subterranean environment supports a unique chemoautotrophic
      microbial community with potentially novel nutrient cycling strategies. These
      strategies may provide key insights into other ecosystems dominated by
      oligotrophy, including aphotic subsurface soils or aquifers and photic systems
      such as arid deserts. 

PMID- 24030598
TI  - Kin recognition in Drosophila: the importance of ecology and gut microbiota.
AB  - The animal gut commonly contains a large reservoir of symbiotic microbes.
      Although these microbes have obvious functions in digestion and immune defence,
      gut microbes can also affect behaviour. Here, we explore whether gut microbiota
      has a role in kin recognition. We assessed whether relatedness, familiarity and
      food eaten during development altered copulation investment in three species of
      Drosophila with diverse ecologies. We found that a monandrous species exhibited
      true kin recognition, whereas familiarity determined kin recognition in a species
      living in dense aggregations. Finally, in a food generalist species, food eaten
      during development masked kin recognition. The effect of food type on copulation
      duration, in addition to the removal of this effect via antibiotic treatment,
      suggests the influence of bacteria associated with the gut. Our results provide
      the first evidence that varied ecologically determined mechanisms of kin
      recognition occur in Drosophila, and that gut bacteria are likely to have a key
      role in these mechanisms. 

PMID- 24030599
TI  - Metagenomic analysis of size-fractionated picoplankton in a marine oxygen minimum
      zone.
AB  - Marine oxygen minimum zones (OMZs) support diverse microbial communities with
      roles in major elemental cycles. It is unclear how the taxonomic composition and
      metabolism of OMZ microorganisms vary between particle-associated and free-living
      size fractions. We used amplicon (16S rRNA gene) and shotgun metagenome
      sequencing to compare microbial communities from large (>1.6 MUm) and small (0.2
      1.6 MUm) filter size fractions along a depth gradient in the OMZ off Chile.
      Despite steep vertical redox gradients, size fraction was a significantly
      stronger predictor of community composition compared to depth. Phylogenetic
      diversity showed contrasting patterns, decreasing towards the anoxic OMZ core in
      the small size fraction, but exhibiting maximal values at these depths within the
      larger size fraction. Fraction-specific distributions were evident for key OMZ
      taxa, including anammox planctomycetes, whose coding sequences were enriched up
      to threefold in the 0.2-1.6 MUm community. Functional gene composition also
      differed between fractions, with the >1.6 MUm community significantly enriched in
      genes mediating social interactions, including motility, adhesion, cell-to-cell
      transfer, antibiotic resistance and mobile element activity. Prokaryotic
      transposase genes were three to six fold more abundant in this fraction,
      comprising up to 2% of protein-coding sequences, suggesting that particle
      surfaces may act as hotbeds for transposition-based genome changes in marine
      microbes. Genes for nitric and nitrous oxide reduction were also more abundant
      (three to seven fold) in the larger size fraction, suggesting microniche
      partitioning of key denitrification steps. These results highlight an important
      role for surface attachment in shaping community metabolic potential and genome
      content in OMZ microorganisms. 

PMID- 24030601
TI  - Site-specific monoubiquitination activates Ras by impeding GTPase-activating
      protein function.
AB  - KRas has recently been shown to be activated by monoubiquitination (mUb). Similar
      to oncogenic mutations, mUb of Ras at position 147 activates Ras by causing a
      defect in GTPase activating protein (GAP) function. To characterize the mechanism
      by which mUb impairs GAP-mediated downregulation of Ras, we made various
      modifications at position 147 of Ras and examined the impact on Ras sensitivity
      to GAP function. Whereas small modifications (iodoacetamide and glutathione) at
      position 147 of Ras do not affect GAP-mediated hydrolysis, ligation of Ras to
      Ub(G76C) (native linker), Ub(X77C) (one residue longer), and PDZ2 (with a native
      ubiquitin linker) was defective in GAP-mediated GTP hydrolysis. However,
      restoration of GAP activity was observed for Ras modified with the PDZ2 domain
      containing a shorter and stiffer linker region than ubiquitin. Therefore, the
      properties of the linker region dictate whether modification affects GAP-mediated
      hydrolysis, and our data indicate that the GAP defect requires a minimum linker
      length of 7 to 8 residues. 

PMID- 24030602
TI  - Ultrafast intersystem-crossing in platinum containing pi-conjugated polymers with
      tunable spin-orbit coupling.
AB  - The development of efficient organic light-emitting diodes (OLED) and organic
      photovoltaic cells requires control over the dynamics of spin sensitive
      excitations. Embedding heavy metal atoms in pi-conjugated polymer chains enhances
      the spin-orbit coupling (SOC), and thus facilitates intersystem crossing (ISC)
      from the singlet to triplet manifolds. Here we use various nonlinear optical
      spectroscopies such as two-photon absorption and electroabsorption in conjunction
      with electronic structure calculations, for studying the energies, emission bands
      and ultrafast dynamics of spin photoexcitations in two newly synthesized pi
      conjugated polymers that contain intrachain platinum (Pt) atoms separated by one
      (Pt-1) or three (Pt-3) organic spacer units. The controllable SOC in these
      polymers leads to a record ISC time of <~1 ps in Pt-1 and ~6 ps in Pt-3. The
      tunable ultrafast ISC rate modulates the intensity ratio of the phosphorescence
      and fluorescence emission bands, with potential applications for white OLEDs. 

PMID- 24030604
TI  - Gangs, violence, and psychiatry.

PMID- 24030603
TI  - Crossmatch-positive liver transplantation in patients receiving thymoglobulin
      rituximab induction.
AB  - BACKGROUND: Positive crossmatch (CM) in liver transplantation (LT) is associated
      with worse outcomes. Role of induction immunosuppression in this setting remains
      to be studied. METHODS: One thousand consecutive LT patients receiving rabbit
      antithymocyte globulin+/-rituximab induction were studied. Pretransplantation
      sera of 55 CM-positive (CM) patients were tested for C1q-fixing donor-specific
      antibodies (DSA). Diagnosis of antibody-mediated rejection required presence of
      diffuse vascular C4d expression on liver biopsies. RESULTS: CM was positive in
      112 (11%) recipients. Antibody-mediated rejection was observed in 3 (0.03%)
      patients, whereas acute cellular rejection (ACR) occurred in 31 (3%) patients. CM
      status was associated with a higher incidence of ACR (9% in CM vs. 2% in CM
      negative [CM]; P<0.01) and chronic rejection (4% in CM vs. 1% in CM; P<0.01).
      Graft survival was slightly lower in CM patients (at 1 year; 85% in CM vs. 89% in
      CM; P=0.26). Patients with autoimmune hepatitis, primary sclerosing cholangitis,
      and primary biliary cirrhosis as a group had a tendency toward CM status as well
      as developing ACR. Upon multivariate analysis, CM status was the strongest
      predictor of ACR (B=1.14; P=0.02). Only half of CM patients harbored C1q-fixing
      DSA. Presence of C1q-fixing DSA was not associated with increased incidence of
      ACR. CONCLUSIONS: In LT, CM status is associated with an increased incidence of
      acute rejection, chronic rejection, and slightly worse graft survival. With the
      use of rabbit antithymocyte globulin+/-rituximab induction, overall low rejection
      rates can be achieved in CM LT.

PMID- 24030605
TI  - Toward rational pharmacotherapy for posttraumatic stress disorder: reprise.

PMID- 24030606
TI  - Metformin for antipsychotic-related weight gain and metabolic abnormalities:
      when, for whom, and for how long?

PMID- 24030607
TI  - Comparative effectiveness of psychodynamic psychotherapy and cognitive-behavioral
      therapy: it's about time, and what's next?

PMID- 24030608
TI  - Psychosis, agitation, and antipsychotic treatment in dementia.

PMID- 24030609
TI  - The psychoses in DSM-5 and in the near future.

PMID- 24030600
TI  - Genomic properties of Marine Group A bacteria indicate a role in the marine
      sulfur cycle.
AB  - Marine Group A (MGA) is a deeply branching and uncultivated phylum of bacteria.
      Although their functional roles remain elusive, MGA subgroups are particularly
      abundant and diverse in oxygen minimum zones and permanent or seasonally
      stratified anoxic basins, suggesting metabolic adaptation to oxygen-deficiency.
      Here, we expand a previous survey of MGA diversity in O2-deficient waters of the
      Northeast subarctic Pacific Ocean (NESAP) to include Saanich Inlet (SI), an
      anoxic fjord with seasonal O2 gradients and periodic sulfide accumulation.
      Phylogenetic analysis of small subunit ribosomal RNA (16S rRNA) gene clone
      libraries recovered five previously described MGA subgroups and defined three
      novel subgroups (SHBH1141, SHBH391, and SHAN400) in SI. To discern the functional
      properties of MGA residing along gradients of O2 in the NESAP and SI, we
      identified and sequenced to completion 14 fosmids harboring MGA-associated 16S
      RNA genes from a collection of 46 fosmid libraries sourced from NESAP and SI
      waters. Comparative analysis of these fosmids, in addition to four publicly
      available MGA-associated large-insert DNA fragments from Hawaii Ocean Time-series
      and Monterey Bay, revealed widespread genomic differentiation proximal to the
      ribosomal RNA operon that did not consistently reflect subgroup partitioning
      patterns observed in 16S rRNA gene clone libraries. Predicted protein-coding
      genes associated with adaptation to O2-deficiency and sulfur-based energy
      metabolism were detected on multiple fosmids, including polysulfide reductase
      (psrABC), implicated in dissimilatory polysulfide reduction to hydrogen sulfide
      and dissimilatory sulfur oxidation. These results posit a potential role for
      specific MGA subgroups in the marine sulfur cycle. 

PMID- 24030610
TI  - An 11-year-old boy with Asperger's disorder presenting with aggression.

PMID- 24030611
TI  - Hair-raising observations: Darwin and Crichton Browne on piloerection and
      insanity.

PMID- 24030612
TI  - Thalamo-cortical activation and connectivity during response preparation in
      adults with persistent and remitted ADHD.
AB  - OBJECTIVE: The neural correlates of stimulus-driven processes, such as response
      preparation, have been posited to be associated with the onset of attention
      deficit hyperactivity disorder (ADHD) while being distinct from the neural
      mechanisms associated with recovery. The authors tested this hypothesis in adults
      with remitted and persistent ADHD. METHOD: Thirty-eight young adults who were
      diagnosed with combined-type ADHD in childhood (probands) and 32 carefully
      matched comparison subjects were followed longitudinally and scanned with
      functional MRI while performing an event-related cued reaction time task.
      Probands were characterized as individuals with persistent or remitted ADHD.
      Differences in thalamo-cortical activation and functional connectivity during
      response preparation between comparison subjects and probands and between
      individuals with persistent ADHD and those with remitted ADHD were assessed by
      contrasting neural activation and functional connectivity during cue or noncue
      events. RESULTS: Probands exhibited less cue-related activation than comparison
      subjects in the thalamus, anterior cingulate cortex, supplementary motor area,
      inferior parietal lobe, and dorsolateral prefrontal cortex despite similar
      overall patterns of activation. There were no differences in activation between
      individuals in the remitted ADHD group and those in the persistent ADHD group in
      any hypothesized regions. However, cue-related functional connectivity between
      the right thalamus and brainstem was greater in comparison subjects relative to
      probands, and cue-related connectivity was greater between the right thalamus and
      prefrontal regions in individuals with remitted ADHD relative to those with
      persistent ADHD. CONCLUSIONS: Decreased thalamo-cortical activation during
      response preparation was present in adults diagnosed with ADHD in childhood
      regardless of symptom remission in adulthood, and may be partly driven by less
      functional coordination between the brainstem and thalamus. Greater functional
      integration of the thalamo-cortical network might parallel symptom recovery.

PMID- 24030614
TI  - Addressing sleep impairment in treatment guidelines for PTSD.

PMID- 24030613
TI  - The efficacy of cognitive-behavioral therapy and psychodynamic therapy in the
      outpatient treatment of major depression: a randomized clinical trial.
AB  - OBJECTIVE: The efficacy of psychodynamic therapies for depression remains open to
      debate because of a paucity of high-quality studies. The authors compared the
      efficacy of psychodynamic therapy with that of cognitive-behavioral therapy
      (CBT), hypothesizing nonsignificant differences and the noninferiority of
      psychodynamic therapy relative to CBT. METHOD: A total of 341 adults who met DSM
      IV criteria for a major depressive episode and had Hamilton Depression Rating
      Scale (HAM-D) scores >=14 were randomly assigned to 16 sessions of individual
      manualized CBT or short-term psychodynamic supportive therapy. Severely depressed
      patients (HAM-D score >24) also received antidepressant medication according to
      protocol. The primary outcome measure was posttreatment remission rate (HAM-D
      score <=7). Secondary outcome measures included mean posttreatment HAM-D score
      and patient-rated depression score and 1-year follow-up outcomes. Data were
      analyzed with generalized estimating equations and mixed-model analyses using
      intent-to-treat samples. Noninferiority margins were prespecified as an odds
      ratio of 0.49 for remission rates and a Cohen's d value of 0.30 for continuous
      outcome measures. RESULTS: No statistically significant treatment differences
      were found for any of the outcome measures. The average posttreatment remission
      rate was 22.7%. Noninferiority was shown for posttreatment HAM-D and patient
      rated depression scores but could not be demonstrated for posttreatment remission
      rates or any of the follow-up measures. CONCLUSIONS: The findings extend the
      evidence base of psychodynamic therapy for depression but also indicate that time
      limited treatment is insufficient for a substantial number of patients
      encountered in psychiatric outpatient clinics.

PMID- 24030615
TI  - Response to Ticlea et al.

PMID- 24030616
TI  - Concomitant use of maintenance ECT and vagus nerve stimulation for more than 10
      years in treatment-resistant depression.

PMID- 24030617
TI  - Life satisfaction among individuals with schizophrenia in the Clinical
      Antipsychotic Trial of Intervention Effectiveness (CATIE) study.

PMID- 24030625
TI  - Letter to the editor: Femoroacetabular impingement predisposes to traumatic
      posterior hip dislocation.

PMID- 24030626
TI  - Can ulnar variance be used to detect overstuffing after radial head arthroplasty?
AB  - BACKGROUND: Overstuffing of the radiocapitellar joint during metallic radial head
      arthroplasty has been reported to cause loss of elbow flexion, capitellar
      erosion, and early-onset osteoarthritis. Although this is known, there is no
      agreed-on measurement approach to determine whether overstuffing has occurred.
      QUESTIONS/PURPOSES: We therefore hypothesized that overlengthening the radial
      head during radial head arthroplasty changes the ulnar variance in the wrist.
      METHODS: Seven cadaveric radii were implanted with radial head prostheses of
      increasing thickness. Each specimen was implanted successively with increasingly
      thick radial head prostheses measuring 2, 4, and 6 mm thicker than the native
      radial head, and radiographs were taken after implantation of each prosthesis.
      The ulnar variance with each prosthesis was measured using the method of
      perpendiculars. RESULTS: The ulnar variance of the native and 2-mm (p = 0.04), 4
      mm (p = 0.008), and 6-mm (p = 0.008) overly thick radial head prosthesis
      implanted states decreased significantly with each incremental increase in
      prosthetic head thickness. CONCLUSIONS: Implantation of thicker radial head
      prostheses decreased the ulnar variance. Our results indicate ulnar variance
      could be used to detect overstuffing of radial head prostheses. CLINICAL
      RELEVANCE: The simplicity and reliability of ulnar variance make it a potentially
      useful indicator of overlengthening after radial head arthroplasty.

PMID- 24030628
TI  - Formation of a dicationic ruthenium benzyl complex by halide abstraction from a
      Grubbs-type second-generation benzylidene.
AB  - A ruthenium benzylidene complex with a neutral bidentate N-heterocyclic carbene
      was prepared and evaluated in ring-closing metathesis of diallyl substrates.
      Reaction with AgPF6 to generate a four-coordinate complex produced an unexpected
      dicationic ruthenium benzyl degradation product through nucleophilic attack of
      the NHC ligand on the benzylidene carbon. 

PMID- 24030627
TI  - Primary intraocular inflammatory myofibroblastic tumor with anaplastic lymphoma
      kinase overexpression.
AB  - The human eye can be compromised by a variated spectrum of neoplasms and reactive
      processes. Here we present a rare case of a primary intraocular inflammatory
      myofibroblastic tumor (IMT) dependent on the sclera and choroid in a 31-year-old
      female. The knowledge surrounding IMTs, previously included in the category of
      inflammatory pseudotumors, has undergone dynamic changes in the past two decades.
      Here we review the characteristics of these tumors in the human eye and in the
      surrounding structures, and we describe the recent advances that allow molecular
      characterization of the neoplastic nature of this entity. 

PMID- 24030629
TI  - Treating rheumatoid arthritis to target: recommendations assessment questionnaire
      in Korea.
AB  - Treat rheumatoid arthritis (RA) to target (T2T) is an international initiative to
      provide the rheumatology community with clear direction on treatment targets for
      RA. We performed a nationwide survey in Korea among rheumatologists to measure
      the levels of agreement with international T2T recommendations and to assess
      their practical application in Korea. A questionnaire was administered to 111
      physicians. Responses were assessed using a 10-point Likert scale for the level
      of agreement with each of 10 recommendations and a 4-point Likert scale for the
      degree to which each recommendation was being applied in current daily practice.
      Respondents were also asked whether these recommendations would result in a
      change in their practice. This report outlines the consensus reached for T2T in
      Korea and compares those results with data obtained internationally. Agreement
      with T2T recommendations was high with average response scores above 8.3. The
      majority of respondents indicated they applied the recommendations "always" and
      "very often" in daily practice. More than half of the participants not currently
      applying these recommendations were willing to change their practice, but the
      percentage of Korean physicians willing to change was consistently more than the
      international average. The results of this survey of T2T recommendations in
      Korean rheumatologists revealed a good correlation with the views of the
      international rheumatology community. These results could be utilized to define
      key issues for better disease control in daily practice and used as a reference
      to improve the treatment environment. 

PMID- 24030630
TI  - Pain mediates the association between physical activity and the impact of
      fibromyalgia on daily function.
AB  - This study quantified the association between recreational physical activity and
      daily function in women with fibromyalgia, and determined if this association is
      mediated by symptoms of pain, depression, or body mass. Twenty-three women
      diagnosed with fibromyalgia participated in an observational survey study.
      Recreational physical activity and the impact of fibromyalgia on daily function
      were assessed using the sport and leisure time physical activity subscales of the
      Baecke Physical Activity Questionnaire (BPAQ) and the Fibromyalgia Impact
      Questionnaire (FIQ), respectively. Potential mediators of the association between
      physical activity and daily function were assessed using the Visual Analogue
      Scale for pain intensity (VAS-Pain), the Beck Depression Inventory (BDI), and
      body mass index (BMI). BPAQ was inversely associated with FIQ (R (2) = 0.20) and
      VAS-Pain (R (2) = 0.39). VAS-Pain was positively associated with FIQ (R (2) =
      0.23). The inverse association between BPAQ and FIQ was no longer significant
      after controlling for VAS-Pain. BDI was positively associated with FIQ (R (2) =
      0.37), whereas BMI was not. BPAQ was not significantly associated with either BDI
      or BMI. These results indicate that the intensity of musculoskeletal pain, rather
      than depressive symptoms or body mass, mediates the association between physical
      activity and daily function among women with fibromyalgia. 

PMID- 24030631
TI  - 177Lu-EC0800 combined with the antifolate pemetrexed: preclinical pilot study of
      folate receptor targeted radionuclide tumor therapy.
AB  - Targeted radionuclide therapy has shown impressive results for the palliative
      treatment of several types of cancer diseases. The folate receptor has been
      identified as specifically associated with a variety of frequent tumor types.
      Therefore, it is an attractive target for the development of new radionuclide
      therapies using folate-based radioconjugates. Previously, we found that
      pemetrexed (PMX) has a favorable effect in reducing undesired renal uptake of
      radiofolates. Moreover, PMX also acts as a chemotherapeutic and radiosensitizing
      agent on tumors. Thus, the aim of our study was to investigate the combined
      application of PMX and the therapeutic radiofolate (177)Lu-EC0800. Determination
      of the combination index (CI) revealed a synergistic inhibitory effect of (177)Lu
      EC0800 and PMX on the viability of folate receptor-positive cervical (KB) and
      ovarian (IGROV-1) cancer cells in vitro (CI < 0.8). In an in vivo study, tumor
      bearing mice were treated with (177)Lu-EC0800 (20 MBq) and a subtherapeutic (0.4
      mg) or therapeutic amount (1.6 mg) of PMX. Application of (177)Lu-EC0800 with
      PMXther resulted in a two- to four-fold enhanced tumor growth delay and a
      prolonged survival of KB and IGROV-1 tumor-bearing mice, as compared to the
      combination with PMXsubther or untreated control mice. PMXsubther protected the
      kidneys from undesired side effects of (177)Lu-EC0800 (20 MBq) by reducing the
      absorbed radiation dose. Intact kidney function was shown by determination of
      plasma parameters and quantitative single-photon emission computed tomography
      using (99m)Tc-DMSA. Our results confirmed the anticipated dual role of PMX. Its
      unique features resulted in an improved antitumor effect of folate-based
      radionuclide therapy and prevented undesired radio-nephrotoxicity.

PMID- 24030632
TI  - The cannabinoid WIN 55,212-2 decreases specificity protein transcription factors
      and the oncogenic cap protein eIF4E in colon cancer cells.
AB  - 2,3-Dihydro-5-methyl-3-([morpholinyl]methyl)pyrollo(1,2,3-de)-1,4-benzoxazinyl]
      [1-naphthaleny]methanone [WIN 55,212-2, (WIN)] is a synthetic cannabinoid that
      inhibits RKO, HT-29, and SW480 cell growth, induced apoptosis, and downregulated
      expression of survivin, cyclin D1, EGF receptor (EGFR), VEGF, and its receptor
      (VEGFR1). WIN also decreased expression of specificity protein (Sp) transcription
      factors Sp1, Sp3, and Sp4, and this is consistent with the observed
      downregulation of the aforementioned Sp-regulated genes. In addition, we also
      observed by RNA interference (RNAi) that the oncogenic cap protein eIF4E was an
      Sp-regulated gene also downregulated by WIN in colon cancer cells. WIN-mediated
      repression of Sp proteins was not affected by cannabinoid receptor antagonists or
      by knockdown of the receptor but was attenuated by the phosphatase inhibitor
      sodium orthovanadate or by knockdown of protein phosphatase 2A (PP2A). WIN
      mediated repression of Sp1, Sp3, and Sp4 was due to PP2A-dependent downregulation
      of microRNA-27a (miR-27a) and induction of miR-27a-regulated ZBTB10, which has
      previously been characterized as an "Sp repressor." The results show that the
      anticancer activity of WIN is due, in part, to PP2A-dependent disruption of miR
      27a:ZBTB10 and ZBTB10-mediated repression of Sp transcription factors and Sp
      regulated genes, including eIF4E.

PMID- 24030633
TI  - PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by
      induction of p73 and Noxa.
AB  - Targeting p53 by the small-molecule PRIMA-1(Met)/APR-246 has shown promising
      preclinical activity in various cancer types. However, the mechanism of PRIMA
      1(Met)-induced apoptosis is not completely understood and its effect on multiple
      myeloma cells is unknown. In this study, we evaluated antitumor effect of PRIMA
      1(Met) alone or its combination with current antimyeloma agents in multiple
      myeloma cell lines, patient samples, and a mouse xenograft model. Results of our
      study showed that PRIMA-1(Met) decreased the viability of multiple myeloma cells
      irrespective of p53 status, with limited cytotoxicity toward normal hematopoietic
      cells. Treatment of multiple myeloma cells with PRIMA-1(Met) resulted in
      induction of apoptosis, inhibition of colony formation, and migration. PRIMA
      1(Met) restored wild-type conformation of mutant p53 and induced activation of
      p73 upregulating Noxa and downregulating Mcl-1 without significant modulation of
      p53 level. siRNA-mediated silencing of p53 showed a little effect on apoptotic
      response of PRIMA-1(Met), whereas knockdown of p73 led to substantial attenuation
      of apoptotic activity in multiple myeloma cells, indicating that PRIMA-1(Met)
      induced apoptosis is, at least in part, p73-dependent. Importantly, PRIMA-1(Met)
      delayed tumor growth and prolonged survival of mice bearing multiple myeloma
      tumor. Furthermore, combined treatment of PRIMA-1(Met) with dexamethasone or
      doxorubicin displayed synergistic effects in both multiple myeloma cell lines and
      primary multiple myeloma samples. Consistent with our in vitro observations,
      cotreatment with PRIMA-1(Met) and dexamethasone resulted in enhanced antitumor
      activity in vivo. Our study for the first time shows antimyeloma activity of
      PRIMA-1(Met) and provides the rationale for its clinical evaluation in patients
      with multiple myeloma, including the high-risk group with p53 mutation/deletion.

PMID- 24030634
TI  - Medicare policy on bariatric surgery: decision making in the face of uncertainty.

PMID- 24030635
TI  - Insulin triggers surface-directed trafficking of sequestered GLUT4 storage
      vesicles marked by Rab10.
AB  - Understanding how glucose transporter isoform 4 (GLUT4) redistributes to the
      plasma membrane during insulin stimulation is a major goal of glucose transporter
      research. GLUT4 molecules normally reside in numerous intracellular compartments,
      including specialized storage vesicles and early/recycling endosomes. It is
      unclear how these diverse compartments respond to insulin stimulation to deliver
      GLUT4 molecules to the plasma membrane. For example, do they fuse with each other
      first or remain as separate compartments with different trafficking
      characteristics? Our recent live cell imaging studies are helping to clarify
      these issues. Using Rab proteins as specific markers to distinguish between
      storage vesicles and endosomes containing GLUT4, we demonstrate that it is
      primarily internal GLUT4 storage vesicles (GSVs) marked by Rab10 that approach
      and fuse at the plasma membrane and GSVs don't interact with endosomes on their
      way to the plasma membrane. These new findings add strong support to the model
      that GSV release from intracellular retention plays a major role in supplying
      GLUT4 molecules onto the PM under insulin stimulation. 

PMID- 24030636
TI  - Sibling concordance for clinical features of Duchenne and Becker muscular
      dystrophies.
AB  - INTRODUCTION: The correlation of markers of disease severity among brothers with
      Duchenne or Becker muscular dystrophy has implications for clinical guidance and
      clinical trials. METHODS: Sibling pairs with Duchenne or Becker muscular
      dystrophy (n = 60) were compared for ages when they reached clinical milestones
      of disease progression, including ceased ambulation, scoliosis of >= 20 degrees ,
      and development of cardiomyopathy. RESULTS: The median age at which younger
      brothers reached each milestone, compared with their older brothers ranged from
      25 months younger for development of cardiomyopathy to 2 months older for ceased
      ambulation. For each additional month of ambulation by the older brother, the
      hazard of ceased ambulation by the younger brother decreased by 4%. CONCLUSIONS:
      The ages when siblings reach clinical milestones of disease vary widely between
      siblings. However, the time to ceased ambulation for older brothers predicts the
      time to ceased ambulation for their younger brothers.

PMID- 24030637
TI  - Ivacaftor: a review of its use in patients with cystic fibrosis.
AB  - Ivacaftor (KalydecoTM) is a potentiator of the cystic fibrosis transmembrane
      conductance regulator (CFTR) and is the first drug that treats an underlying
      cause of cystic fibrosis to be licensed for use. Ivacaftor increases the open
      probability (i.e. gating) of CFTR channels with the G551D mutation, thus
      enhancing chloride transport, and is indicated in a number of countries for the
      treatment of cystic fibrosis in patients aged >=6 years who carry this mutation.
      This review focuses on pharmacological, clinical efficacy and tolerability data
      relevant to the use of ivacaftor in this indication. In two 48-week, double
      blind, phase III trials in patients aged >=12 (STRIVE) or 6-11 (ENVISION) years
      with cystic fibrosis and the G551D mutation, oral ivacaftor 150 mg every 12 h
      significantly improved lung function relative to placebo, when used in
      combination with standard care. Significant improvements in pulmonary
      exacerbation risk (in STRIVE) as well as bodyweight and some aspects of health
      related quality of life (both studies) were also seen with the drug versus
      placebo. Moreover, the beneficial effects of ivacaftor on parameters such as lung
      function and bodyweight were maintained over up to 96 weeks of treatment in an
      ongoing open-label extension of these studies. Ivacaftor was generally well
      tolerated, with headache, oropharyngeal pain, upper respiratory tract infection
      and nasal congestion being among the most common adverse events. Thus, ivacaftor
      expands the current treatment options for patients with cystic fibrosis who have
      the G551D mutation. Its potential for use in patients with other CFTR mutations
      is also of interest. 

PMID- 24030638
TI  - NKG2C zygosity influences CD94/NKG2C receptor function and the NK-cell
      compartment redistribution in response to human cytomegalovirus.
AB  - Human cytomegalovirus (HCMV) infection promotes a persistent expansion of a
      functionally competent NK-cell subset expressing the activating CD94/NKG2C
      receptor. Factors underlying the wide variability of this effect observed in HCMV
      seropositive healthy individuals and exacerbated in immunocompromized patients
      are uncertain. A deletion of the NKG2C gene has been reported, and an apparent
      relation of NKG2C genotype with circulating NKG2C(+) NK-cell numbers was observed
      in HCMV(+) children. We have assessed the influence of NKG2C gene dose on the NK
      cell repertoire in a cohort of young healthy adults (N = 130, median age 19
      years). Our results revealed a relation of NKG2C copy number with surface
      receptor levels and with NKG2C(+) NK-cell numbers in HCMV(+) subjects,
      independently of HLA-E dimorphism. Functional studies showed quantitative
      differences in signaling (i.e. iCa(2+) influx), degranulation, and IL-15
      dependent proliferation, in response to NKG2C engagement, between NK cells from
      NKG2C(+/+) and hemizygous subjects. These observations provide a mechanistic
      interpretation on the way the NKG2C genotype influences steady-state NKG2C(+) NK
      cell numbers, further supporting an active involvement of the receptor in the
      HCMV-induced reconfiguration of the NK-cell compartment. The putative
      implications of NKG2C zygosity over viral control and other clinical variables
      deserve attention. 

PMID- 24030639
TI  - Mutational analysis of the stability of Psb27 from Synechocystis sp. PCC 6803:
      implications for models of Psb27 structure and binding to CP43.
AB  - Psb27 associates with the CP43 subunit of photosystem II during biogenesis of the
      photosystem. Several models have been proposed for the interaction between Psb27
      and CP43. The utility of predictions and hypotheses arising from these models
      depends on the accuracy of the Psb27 structure used in the model. Two of the
      Psb27 structures used to model the Psb27-CP43 interaction place residue E98 on
      the surface of Psb27 and D14 in a position to form hydrogen bonds that stabilise
      the fold of the protein; however, a third structure questions the surface
      exposure of E98 and does not identify significant interactions of D14. Here we
      present evidence that D14 contributes to the thermal stability of Psb27 and that
      E98 is located on the surface. A D14A mutation was shown to reduce the apparent
      midpoint of unfolding of Psb27 by 16  degrees C. Four highly conserved surface
      residues and E98 were subject to charge-reversal mutations (R54E, R94E, E98R,
      E103R, R108E). The stabilities of the charge-reversal variants and the unmodified
      control were similar, suggesting E98 is a surface residue. Placing E98 in the
      correct, surface position will support more reliable models of the interaction of
      Psb27 with CP43.

PMID- 24030640
TI  - NO3 radical production from the reaction between the Criegee intermediate CH2OO
      and NO2.
AB  - Formation of the NO3 radical was observed following photolysis of the CH2I2 + O2
      system at 248 nm under ambient atmospheric boundary layer conditions (~760 Torr
      and 297 K) in the presence of NO2. The Criegee intermediate (CI) CH2OO is
      believed to be responsible for the NO3 production. The potential of such
      reactions to enhance the rate of NO3 production in the atmosphere is discussed.

PMID- 24030641
TI  - The benefits of international postdoctoral research fellowships: a personal
      perspective.

PMID- 24030645
TI  - Hair follicle signaling networks: a dermal papilla-centric approach.
AB  - Functional testing of dermal papilla (DP) signaling inputs into hair follicle
      (HF) morphogenesis and regeneration is becoming possible with the advent of new
      Cre lines. Targeted deletion of the signature genes in early DP precursors has
      revealed significant signaling redundancy during HF morphogenesis. Furthermore,
      the DP lineage commitment program can be exploited for generating highly
      inductive DP cells to be used in HF bioengineering assays. 

PMID- 24030646
TI  - Psoriasis and cardiovascular disease: where is the risk?
AB  - In this issue, Dowlatshahi et al. publish results from their population-based
      study in Rotterdam showing that, despite an increase in body mass index and
      smoking, individuals with psoriasis have no increased risk of incident
      cardiovascular disease. These results should be interpreted with caution: the
      study included relatively small numbers of patients with psoriasis, most of whom
      had mild disease. 

PMID- 24030647
TI  - Mechanisms of contact sensitization offer insights into the role of barrier
      defects vs. intrinsic immune abnormalities as drivers of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common inflammatory skin disease characterized by
      wet, oozing, erythematous, pruritic lesions in the acute stage and xerotic,
      lichenified plaques in the chronic stage. It frequently coexists with asthma and
      allergic rhinitis, sharing some mechanistic features with these diseases as part
      of the "atopic march." Controversy exists as to whether immune abnormalities,
      epidermal barrier defects, or both are the primary factors responsible for
      disease pathogenesis. In AD patients, there is often a coexisting irritant
      contact dermatitis (ICD) or allergic contact dermatitis (ACD) that is sometimes
      clinically difficult to distinguish from AD. ACD shares molecular mechanisms with
      AD, including increased cellular infiltrates and cytokine activation (Gittler et
      al., 2013). In this issue, Newell et al. (2013) used an experimental contact
      sensitization model with dinitrochlorobenzene (DNCB) to gain insight into the
      unique immune phenotype of AD patients. 

PMID- 24030648
TI  - Glucocorticoids in autoimmune bullous diseases: are neutrophils the key cellular
      target?
AB  - The newly observed nongenomic effects of glucocorticoids on signaling pathways
      operating in neutrophils in vitro will stimulate further investigations on
      pathogenic mechanisms and drug actions in bullous skin diseases. 

PMID- 24030649
TI  - Change is in the air: the hypoxic induction of phenotype switching in melanoma.
AB  - Melanoma cells can switch from a highly proliferative, less invasive state to a
      highly invasive, less proliferative state, a phenomenon termed phenotype
      switching. This results in a highly heterogenous tumor, where a slow-growing,
      aggressive population of cells may resist tumor therapy, and it predicts tumor
      recurrence. Here we discuss the observation made by Widmer et al. that hypoxia
      may drive phenotype switching. 

PMID- 24030650
TI  - "Validation" of outcome measures in dermatology.

PMID- 24030651
TI  - JID VisualDx quiz: October 2013.

PMID- 24030652
TI  - Male vocal competition is dynamic and strongly affected by social contexts in
      music frogs.
AB  - Male-male vocal competition in anuran species is critical for mating success;
      however, it is also highly time-consuming, energetically demanding and likely to
      increase predation risks. Thus, we hypothesized that changes in the social
      context would cause male vocal competition to change in real time in order to
      minimize the costs and maximize the benefits of competition. To test this
      hypothesis, we assessed the effect of repeating playbacks of either white noise
      (WN) or male advertisement calls on male call production in the Emei music frog
      (Babina daunchina), a species in which males build mud-retuse burrows and call
      from within these nests. Previous studies have shown that calls produced from
      inside burrows are highly sexually attractive (HSA) to females while those
      produced outside nests are of low sexual attractiveness (LSA). Results showed
      that most subjects called responsively after the end of WN playbacks but before
      the onset of conspecific call stimuli although call numbers were similar,
      indicating that while males adjusted competitive patterns according to the
      biological significance of signals, their competitive motivation did not change.
      Furthermore, these data indicate that the frogs had evolved the ability of
      interval timing. Moreover, when the inter-stimulus interval (ISI) between
      playbacks was varied, the subjects preferentially competed with HSA calls when
      the ISI was short (<4 s) but responded equally to HSA and LSA calls if the ISI
      was long (>=4 s), suggesting that males allocate competitive efforts depending on
      both the perceived sexual attractiveness of rivals and the time available for
      calling. Notably, approximately two-thirds of male calls occurred in response to
      HSA calls, a preference rate comparable to that previously found for females in
      phonotaxis experiments and consistent with the idea that the mechanisms
      underlying both the male's competitive responses to rivals and the female's
      preferences toward potential mates coevolved under the same selective pressure. 

PMID- 24030654
TI  - Interference in pheromone-responsive conjugation of a high-level bacitracin
      resistant Enterococcus faecalis plasmid of poultry origin.
AB  - The current study reports on contact interference of a high-level bacitracin-
      resistant pheromone-responsive plasmid of Enterococcus faecalis strain 543 of
      poultry origin during conjugative transfer of bcr antimicrobial resistance genes
      using a polyclonal antiserum aggregation substance(44-560) (AS). After induction
      with pheromones produced by the recipient strain E. faecalis JH2-2, clumping of
      the donor E. faecalis strain 543 was observed as well as high transfer
      frequencies of bcr in short time broth mating. Filter mating assays from donor
      strain E. faecalis 543 to the recipient strain E. faecalis JH2-2 revealed
      conjugative transfer of asa1 (AS), bcrRAB and traB (negative regulator pheromone
      response) genes. The presence of these genes in transconjugants was confirmed by
      antimicrobial susceptibility testing, PCR, Southern hybridization and sequencing.
      A significant reduction in formation of aggregates was observed when the
      polyclonal anti-AS(44-560) was added in the pheromone-responsive conjugation
      experiments as compared to the induced state. Moreover, interference of anti
      AS(44-560) antibodies in pheromone-responsive conjugation was demonstrated by a
      reduction in horizontal transfer of asa1 and bcr genes between E. faecalis strain
      543 and E. faecalis JH2-2. Reducing the pheromone-responsive conjugation of E.
      faecalis is of interest because of its clinical importance in the horizontal
      transfer of antimicrobial resistance.

PMID- 24030656
TI  - A novel "continuous-interrupted" method for microvascular anastomosis.

PMID- 24030655
TI  - Epigenetic findings in autism: new perspectives for therapy.
AB  - Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental
      disorders characterized by dysfunctions in social interactions, communications,
      restricted interests, and repetitive stereotypic behaviors. Despite extensive
      genetic and biological research, significant controversy surrounds our
      understanding of the specific mechanisms of their pathogenesis. However,
      accumulating evidence points to the involvement of epigenetic modifications as
      foundational in creating ASD pathophysiology. Epigenetic modifications or the
      alteration of DNA transcription via variations in DNA methylation and histone
      modifications but without alterations in the DNA sequence, affect gene
      regulation. These alterations in gene expression, obtained through DNA
      methylation and/or histone modifications, result from transcriptional regulatory
      influences of environmental factors, such as nutritional deficiencies, various
      toxicants, immunological effects, and pharmaceuticals. As such these effects are
      epigenetic regulators which determine the final biochemistry and physiology of
      the individual. In contrast to psychopharmacological interventions, bettering our
      understanding of how these gene-environmental interactions create autistic
      symptoms should facilitate the development of therapeutic targeting of gene
      expression for ASD biomedical care. 

PMID- 24030657
TI  - Silicone gel sheeting for preventing and treating hypertrophic and keloid scars.
AB  - BACKGROUND: Keloid and hypertrophic scars are common and are caused by a
      proliferation of dermal tissue following skin injury. They cause functional and
      psychological problems for patients, and their management can be difficult. The
      use of silicone gel sheeting to prevent and treat hypertrophic scarring is still
      relatively new and started in 1981 with treatment of burn scars. OBJECTIVES: To
      determine the effectiveness of silicone gel sheeting for:(1) prevention of
      hypertrophic or keloid scarring in people with newly healed wounds (e.g. post
      surgery);(2) treatment of established scarring in people with existing keloid or
      hypertrophic scars. SEARCH METHODS: In May 2013 we searched the Cochrane Wounds
      Group Specialised Register; the Cochrane Central Register of Controlled Trials
      (CENTRAL); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations);
      Ovid EMBASE; and EBSCO CINAHL for this second update. SELECTION CRITERIA: Any
      randomised or quasi-randomised controlled trials, or controlled clinical trials,
      comparing silicone gel sheeting for prevention or treatment of hypertrophic or
      keloid scars with any other non surgical treatment, no treatment or placebo. DATA
      COLLECTION AND ANALYSIS: We assessed all relevant trials for methodological
      quality. Three review authors extracted data independently using a standardised
      form and cross-checked the results. We assessed all trials meeting the selection
      criteria for methodological quality. MAIN RESULTS: We included 20 trials
      involving 873 people, ranging in age from 1.5 to 81 years. The trials compared
      adhesive silicone gel sheeting with no treatment; non silicone dressing; other
      silicone products; laser therapy; triamcinolone acetonide injection; topical
      onion extract and pressure therapy. In the prevention studies, when compared with
      a no treatment option, whilst silicone gel sheeting reduced the incidence of
      hypertrophic scarring in people prone to scarring (risk ratio (RR) 0.46, 95%
      confidence interval (CI) 0.21 to 0.98) these studies were highly susceptible to
      bias. In treatment studies, silicone gel sheeting produced a statistically
      significant reduction in scar thickness (mean difference (MD) -2.00, 95% CI -2.14
      to -1.85) and colour amelioration (RR 3.49, 95% CI 1.97 to 6.15) but again these
      studies were highly susceptible to bias. AUTHORS' CONCLUSIONS: There is weak
      evidence of a benefit of silicone gel sheeting as a prevention for abnormal
      scarring in high-risk individuals but the poor quality of research means a great
      deal of uncertainty prevails. Trials evaluating silicone gel sheeting as a
      treatment for hypertrophic and keloid scarring showed improvements in scar
      thickness and scar colour but are of poor quality and highly susceptible to bias.

PMID- 24030658
TI  - Enantioselective ring-opening of meso-epoxides by aromatic amines catalyzed by a
      homochiral metal-organic framework.
AB  - The enantioselective ring-opening of meso-epoxides by aromatic amines was
      achieved by using a new chiral metal-organic framework . The corresponding alpha
      hydroxyamines were obtained with good yields and ee values (up to 89% ee). 

PMID- 24030659
TI  - Importance of co-donor field strength in the preparation of tetradentate alpha
      diimine nickel hydrosilylation catalysts.
AB  - Although bis(alpha-diimine)Ni complexes were prepared when amine-substituted
      chelates were added to Ni(COD)2, the incorporation of strong-field phosphine
      donors allowed the isolation of (kappa(4)-N,N,P,P-DI)Ni hydrosilylation
      catalysts. The crystallographic investigation of two different (kappa(4)-N,N,P,P
      DI)Ni compounds revealed that the geometry about nickel influences the observed
      degree of alpha-diimine reduction. 

PMID- 24030660
TI  - Lengthening the short nose in Asians: key maneuvers and surgical results.
AB  - IMPORTANCE: Using objective anthropometric measurement, this study reports the
      outcome of surgical correction of short-nose deformities in Asian patients.
      OBJECTIVE: To present our experience in lengthening the short nose in Asians and
      report the surgical results. DESIGN, SETTING, AND PATIENTS: In this retrospective
      review, we study the cases of 36 patients who underwent surgical correction of
      short-nose deformity. The effect of nasal lengthening was analyzed using
      anthropometric measurement, including nasion to tip-defining point (N-TDP), nasal
      tip projection (NTP), nasofrontal angle (NFA), and columellar-facial angle (CFA).
      EXPOSURES: Surgical correction of short-nose deformity. MAIN OUTCOME MEASURES:
      The preoperative and postoperative N-TDP, NTP, NFA, and CFA and patient
      satisfaction. RESULTS: The mean postoperative follow-up duration was 29.8 months.
      The cause of the short nose was congenital in 18 cases and secondary to previous
      rhinoplasty in 18 cases. Septal tissue, conchal cartilage, costal cartilage, and
      conchal composite tissue were used as graft materials. The key procedures for
      lengthening included septal extension graft reinforced with extended spreader,
      dorsal onlay, and tip grafts. The N-TDP increased by 11.2%, and CFA decreased
      from 122.6 degrees  to 111.1 degrees . The NFA changed from 148.9 degrees  to
      148.5 degrees . The NTP ratio, measured using the Goode method, decreased from
      0.53 to 0.50. The increase of N-TDP was greater in patients undergoing the costal
      cartilage grafting procedure than in those who received septal or conchal
      cartilage. All patients were satisfied with the aesthetic results, and there were
      no serious complications. CONCLUSIONS AND RELEVANCE: In Asians, the key maneuvers
      for lengthening were septal extension graft reinforced with extended spreader and
      dorsal onlay graft. Rib cartilage provided superior lengthening effect compared
      with other cartilage. LEVEL OF EVIDENCE: 4.

PMID- 24030661
TI  - Probing the interplay between quantum charge fluctuations and magnetic ordering
      in LuFe2O4.
AB  - The mechanisms producing strong coupling between electric and magnetic order in
      multiferroics are not always well understood, since their microscopic origins can
      be quite different. Hence, gaining a deeper understanding of magnetoelectric
      coupling in these materials is the key to their rational design. Here, we use
      ultrafast optical spectroscopy to show that the influence of magnetic ordering on
      quantum charge fluctuations via the double-exchange mechanism can govern the
      interplay between electric polarization and magnetism in the charge-ordered
      multiferroic LuFe2O4. 

PMID- 24030662
TI  - Effect of terbutaline on hyperpnoea-induced bronchoconstriction and urinary club
      cell protein 16 in athletes.
AB  - Repeated injury of the airway epithelium caused by hyperpnoea of poorly
      conditioned air has been proposed as a key factor in the pathogenesis of exercise
      induced bronchoconstriction (EIB) in athletes. In animals, the short-acting beta2
      agonist terbutaline has been shown to reduce dry airflow-induced
      bronchoconstriction and the associated shedding of airway epithelial cells. Our
      aim was to test the efficacy of inhaled terbutaline in attenuating hyperpnoea
      induced bronchoconstriction and airway epithelial injury in athletes. Twenty
      seven athletes with EIB participated in a randomized, double-blind, placebo
      controlled, crossover study. Athletes completed an 8-min eucapnic voluntary
      hyperpnoea (EVH) test with dry air on two separate days 15 min after inhaling 0.5
      mg terbutaline or a matching placebo. Forced expiratory volume in 1 s (FEV1) and
      urinary concentration of the club cell (Clara cell) protein 16 (CC16, a marker of
      airway epithelial perturbation) were measured before and up to 60 min after EVH.
      The maximum fall in FEV1 of 17 +/- 8% (SD) on placebo was reduced to 8 +/- 5%
      following terbutaline (P < 0.001). Terbutaline gave bronchoprotection (i.e., post
      EVH FEV1 fall <10%) to 22 (81%) athletes. EVH caused an increase in urinary
      excretion of CC16 in both conditions (P < 0.001), and terbutaline significantly
      reduced this rise (pre- to postchallenge CC16 increase 416 +/- 495 pg/MUmol
      creatinine after placebo vs. 315 +/- 523 pg/MUmol creatinine after terbutaline, P
      = 0.016). These results suggest that the inhalation of a single therapeutic dose
      of terbutaline offers significant protection against hyperpnoea-induced
      bronchoconstriction and attenuates acute airway epithelial perturbation in
      athletes. 

PMID- 24030663
TI  - Tibetans living at sea level have a hyporesponsive hypoxia-inducible factor
      system and blunted physiological responses to hypoxia.
AB  - Tibetan natives have lived on the Tibetan plateau (altitude ~ 4,000 m) for at
      least 25,000 years, and as such they are adapted to life and reproduction in a
      hypoxic environment. Recent studies have identified two genetic loci, EGLN1 and
      EPAS1, that have undergone natural selection in Tibetans, and further
      demonstrated an association of EGLN1/EPAS1 genotype with hemoglobin
      concentration. Both genes encode major components of the hypoxia-inducible factor
      (HIF) transcriptional pathway, which coordinates an organism's response to
      hypoxia. Patients living at sea level with genetic disease of the HIF pathway
      have characteristic phenotypes at both the integrative-physiology and cellular
      level. We sought to test the hypothesis that natural selection to hypoxia within
      Tibetans results in related phenotypic differences. We compared Tibetans living
      at sea level with Han Chinese, who are Tibetans' most closely related major
      ethnic group. We found that Tibetans had a lower hemoglobin concentration, a
      higher pulmonary ventilation relative to metabolism, and blunted pulmonary
      vascular responses to both acute (minutes) and sustained (8 h) hypoxia. At the
      cellular level, the relative expression and hypoxic induction of HIF-regulated
      genes were significantly lower in peripheral blood lymphocytes from Tibetans
      compared with Han Chinese. Within the Tibetans, we found a significant
      correlation between both EPAS1 and EGLN1 genotype and the induction of
      erythropoietin by hypoxia. In conclusion, this study provides further evidence
      that Tibetans respond less vigorously to hypoxic challenge. This is evident at
      sea level and, at least in part, appears to arise from a hyporesponsive HIF
      transcriptional system.

PMID- 24030665
TI  - Effects of acute exercise on flow-mediated dilatation in healthy humans.
AB  - Although the effects of exercise training on vascular function have been well
      studied, less is known about the effects of acute exercise bouts. This synthesis
      summarizes and integrates knowledge derived from papers relating acute impacts of
      exercise on artery function, specifically endothelial function assessed by flow
      mediated dilatation (FMD). We propose that an immediate decrease in FMD ("nadir")
      occurs soon after exercise cessation and that this is followed by a
      (supra)normalization response. The magnitude of the nadir and
      (supra)normalization and duration of this biphasic pattern of response appears to
      be influenced by numerous factors, including the nature of the exercise stimulus
      (e.g., type, duration, intensity), the subject population (e.g., trained vs.
      untrained), and various methodological factors. The impact of these factors on
      the biphasic pattern are most likely mediated through stimuli that underpin
      altered FMD postexercise, including shear and oxidative stress, changes in
      arterial diameter, and antioxidant status. We propose that a combination of these
      stimuli act synergistically to balance the vasomotor responses postexercise.
      Finally, we discuss the potential (clinical) relevance of the biphasic response
      after acute exercise, as the immediate nadir may represent an essential response
      for subsequent training-induced adaptations but may also represent a transient
      period of increased cardiovascular risk leading to the "exercise paradox." 

PMID- 24030664
TI  - The von Hippel-Lindau Chuvash mutation in mice causes carotid-body hyperplasia
      and enhanced ventilatory sensitivity to hypoxia.
AB  - The hypoxia-inducible factor (HIF) family of transcription factors coordinates
      diverse cellular and systemic responses to hypoxia. Chuvash polycythemia (CP) is
      an autosomal recessive disorder in humans in which there is impaired oxygen
      dependent degradation of HIF, resulting in long-term systemic elevation of HIF
      levels at normal oxygen tensions. CP patients demonstrate the characteristic
      features of ventilatory acclimatization to hypoxia, namely, an elevated baseline
      ventilation and enhanced acute hypoxic ventilatory response (AHVR). We
      investigated the ventilatory and carotid-body phenotype of a mouse model of CP,
      using whole-body plethysmography, immunohistochemistry, and electron microscopy.
      In keeping with studies in humans, CP mice had elevated ventilation in euoxia and
      a significantly exaggerated AHVR when exposed to 10% oxygen, with or without the
      addition of 3% carbon dioxide. Carotid-body immunohistochemistry demonstrated
      marked hyperplasia of the oxygen-sensing type I cells, and the cells themselves
      appeared enlarged with more prominent nuclei. This hypertrophy was confirmed by
      electron microscopy, which also revealed that the type I cells contained an
      increased number of mitochondria, enlarged dense-cored vesicles, and markedly
      expanded rough endoplasmic reticulum. The morphological and ultrastructural
      changes seen in the CP mouse carotid body are strikingly similar to those
      observed in animals exposed to chronic hypoxia. Our study demonstrates that the
      HIF pathway plays a major role, not only in regulating both euoxic ventilatory
      control and the sensitivity of the response to hypoxia, but also in determining
      the morphology of the carotid body. 

PMID- 24030666
TI  - Towards valid estimates of activity energy expenditure using an accelerometer:
      searching for a proper analytical strategy and big data.

PMID- 24030667
TI  - Combined (99m)Tc-methoxyisobutylisonitrile scintigraphy and fine-needle
      aspiration cytology offers an accurate and potentially cost-effective
      investigative strategy for the assessment of solitary or dominant thyroid
      nodules.
AB  - PURPOSE: Fine-needle aspiration (FNA) has revolutionised the care of patients
      with thyroid nodules and is the initial investigation of choice. However, as a
      result of nondiagnostic (Thy1) and nonneoplastic (Thy2) specimens, it remains an
      imperfect sole solution with a range of sensitivities and a high inadequate
      ratio. Therefore the British Thyroid Association (BTA) guidelines recommend a
      second FNA immediately for Thy1 specimens and 3-6 months later for Thy2
      specimens. Patients must be followed up to exclude malignancy. In this study we
      assessed the performance of MIBI scintigraphy for diagnosing thyroid malignancy
      and the cost-effectiveness of a combined FNA/MIBI investigative strategy for the
      management of thyroid nodules. METHODS: The diagnostic performance of MIBI
      scintigraphy was calculated from a retrospective review of local data combined
      with a meta-analysis of the published literature. Decision tree analysis was used
      to calculate the cost-effectiveness of a combined FNA/MIBI investigative strategy
      compared to the BTA guidelines. RESULTS: From 712 patients, the sensitivity,
      specificity, PPV and NPV of MIBI scintigraphy for the diagnosis of malignancy
      were 96 %, 46 %, 34 % and 97 %, respectively. MIBI-based strategies were more
      accurate and associated with lower cost per patient (L1,855/<euro>2,125 vs.
      L2,445/<euro>2,801) and lower cost per cancer diagnosed (L1,902/<euro>2,179 vs.
      L2,469/<euro>2,828) with negligible change in life expectancy. CONCLUSION: Due to
      its high NPV, MIBI scintigraphy can usefully exclude malignancy for Thy1 and Thy2
      lesions. Its low specificity means MIBI scintigraphy cannot be recommended as a
      first-line investigation, but as a second-line investigation MIBI scintigraphy
      may lead to a lower rate of unnecessary thyroidectomies. Combined FNA/MIBI
      strategies are potentially cost-effective in the management of solitary or
      dominant thyroid nodules.

PMID- 24030668
TI  - Outcome and toxicity of salvage therapy with 177Lu-octreotate in patients with
      metastatic gastroenteropancreatic neuroendocrine tumours.
AB  - PURPOSE: We assessed the outcome and toxicity of salvage therapy (repeat
      treatment) with (177)Lu-octreotate and high cumulative activities in patients
      with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET). METHODS:
      We retrospectively analysed a consecutive cohort of 33 patients with metastatic
      GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our
      institution. All patients had progressive NET prior to salvage treatment and had
      shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq
      (30.0-83.7 GBq). Radiographic response was assessed using CT and/or MRI according
      to modified SWOG criteria. Toxicity was evaluated using laboratory data,
      including complete blood counts and renal function tests using CTCAE 3.0.
      Survival analysis was performed with the Kaplan-Meier curve method and a
      significance level at p < 0.05. RESULTS: Radiographic responses consisted of
      complete response in 1 patient (3.0%), partial response in 6 patients (18.2%),
      minor response in 1 patient (3.0%), stable disease in 14 patients (42.4%), and
      progressive disease in 11 patients (33.3%). Median progression-free survival
      (PFS) from the start of salvage therapy was 13 months (95% CI 9-18) and patients
      with a history of a durable PFS after initial PRRT tended to have long-lasting
      PFS after salvage treatment (p = 0.04). None of the patients developed severe
      nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up.
      Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients
      (21.2%). The cumulative administered activity was not associated with an
      increased incidence of haematotoxicity. CONCLUSION: PRRT with (177)Lu-octreotate
      in the re-treatment setting is safe and effective in patients with metastatic GEP
      NET.

PMID- 24030669
TI  - Feasibility of temporary protective embolization of normal liver tissue using
      degradable starch microspheres during radioembolization of liver tumours.
AB  - PURPOSE: To describe a new approach to protect nontarget healthy liver tissue
      using degradable starch microspheres (DSM) as a short-term embolizate during
      radioembolization of liver tumours with (90)Y microspheres. METHODS: Between
      December 2011 and July 2012 radioembolization was performed in 54 patients. Five
      of these patients (three women, two men; mean age 67 years) underwent protective
      temporary embolization using DSM (EmboCept(r) S) of normal liver tissue that
      could not be excluded from the area treated by radioembolization through catheter
      repositioning. Clinical symptoms, laboratory findings, preinterventional imaging,
      and (99m)Tc-MAA and bremsstrahlung SPECT/CT, as well as baseline and follow-up
      imaging with (18)F-FDG PET/CT and MRI, were evaluated in relation to the
      technical and clinical success of the protective embolization. RESULTS: Temporary
      embolization of arteries supplying normal liver tissue using DSM was technically
      successful in all five patients. (99m)Tc-MAA SPECT/CT performed in the first two
      patients after DSM injection showed no increased pulmonary shunting compared to
      the MAA test injection without DSM. Bremsstrahlung SPECT/CT after
      radioembolization demonstrated satisfactory irradiation of the tumour and
      successful protection of normal liver tissue. There were only mild hepatotoxic
      effects (grade 1) on laboratory follow-up examinations, and no adverse events
      associated with DSM embolization or radioembolization were recorded. CONCLUSION:
      Temporary embolization with DSM before radioembolization is feasible and can
      effectively protect areas of normal liver tissue from irradiation and avoid
      permanent embolization if other methods such as catheter repositioning are not
      possible due to the location of the metastases.

PMID- 24030670
TI  - Low-dose single acquisition rest (99m)Tc/stress (201)Tl myocardial perfusion
      SPECT protocol: phantom studies and clinical validation.
AB  - PURPOSE: We developed and tested a single acquisition rest (99m)Tc
      sestamibi/stress (201)Tl dual isotope protocol (SDI) with the intention of
      improving the clinical workflow and patient comfort of myocardial perfusion
      single photon emission computed tomography (SPECT). METHODS: The technical
      feasibility of SDI was evaluated by a series of anthropomorphic phantom studies
      on a standard SPECT camera. The attenuation map was created by a moving
      transmission line source. Iterative reconstruction including attenuation
      correction, resolution recovery and Monte Carlo simulation of scatter was used
      for simultaneous reconstruction of dual tracer distribution. For clinical
      evaluation, patient studies were compared to stress (99m)Tc and rest (99m)Tc
      reference images acquired in a 2-day protocol. Clinical follow-up examinations
      like coronary angiography (CAG) and fractional flow reserve (FFR) were included
      in the assessment if available. RESULTS: Phantom studies demonstrated the
      technical feasibility of SDI. Artificial lesions inserted in the phantom
      mimicking ischaemia could be clearly identified. In 51/53 patients, the image
      quality was adequate for clinical evaluation. For the remaining two obese
      patients with body mass index > 32 the injected (201)Tl dose of 74 MBq was
      insufficient for clinical assessment. In answer to this the (201)Tl dose was
      adapted for obese patients in the rest of the study. In 31 patients, SDI and
      (99m)Tc reference images resulted in equivalent clinical assessment. Significant
      differences were found in 20 patients. In 18 of these 20 patients additional
      examinations were available. In 15 patients the diagnosis based on the SDI images
      was confirmed by the results of CAG or FFR. In these patients the SDI images were
      more accurate than the (99m)Tc reference study. In three patients minor ischaemic
      lesions were detected by SDI but were not confirmed by CAG. In one of these cases
      this was probably caused by pronounced apical thinning. For two patients no
      relevant clinical follow-up information was available for evaluation. CONCLUSION:
      The proposed SDI protocol has the potential to improve clinical workflow and
      patient comfort and suggests improved accuracy as demonstrated in the clinical
      feasibility study.

PMID- 24030671
TI  - Minimally invasive aortic valve replacement with Perceval valves: first clinical
      experience.
AB  - AIM: Although minimally invasive aortic valve replacement (MIAVR) has been shown
      to cause less morbidity than conventional surgery, it has not yet received broad
      application. The purpose of this study was to evaluate sutureless implantation
      using the Perceval S aortic valve bioprosthesis (Sorin Group, Saluggia, Italy)
      via ministernotomy. METHODS: Seventy-two patients (43 women, 29 men; mean age
      77.4 +/- 5.3 years) with isolated aortic valve stenosis (mean gradient of 52 +/-
      14 mmHg) underwent aortic valve implantation with the sutureless Perceval S
      bioprosthesis, following cardiopulmonary bypass (CPB), aortic cross-clamping
      (ACC), cardioplegic arrest and removal of the calcified native valve. The mean
      logistic EuroSCORE was 9.7 +/- 6.2%. RESULTS: The prosthetic valve was
      successfully deployed in all patients. Thirty-day mortality was 1.4% (n = 1).
      Mean CBP, ACC, and implantation times were 68 +/- 18, 40 +/- 13 and 8.9 +/- 4
      min, respectively. Perioperative echocardiography revealed significant
      paravalvular leakage in one patient. Postoperative mean gradient was 11.6 +/- 5.1
      mmHg. At a mean follow-up of 13 +/- 6.7 months, no significant paravalvular
      leakage or valvular regurgitation was observed, and no migration or dislodgement
      of the prosthesis occurred. CONCLUSION: This study shows that sutureless
      implantation of the Perceval S aortic valve bioprosthesis provides a simple and
      reproducible alternative for MIAVR. As the valve does not need to be sutured, it
      may also result in reduced ACC and CPB times. This self-anchoring valve may also
      allow the application of MIAVR to a broader spectrum of patients. This new
      technology needs a long-term follow-up.

PMID- 24030672
TI  - Anticoagulant treatment is effective in atrial fibrillation.

PMID- 24030673
TI  - Author's reply to Robson and Lip.

PMID- 24030674
TI  - Perinatal factors relating to changes in maternal body fat in late gestation.
AB  - OBJECTIVE: To examine changes in skinfolds in late gestation in healthy women.
      STUDY DESIGN: Skinfold measures were performed in 39 women at 30.8 (mean) and
      37.7 weeks gestation. Fat mass (kg) and sum of three skinfolds were calculated.
      RESULTS: A decrease in skinfold thickness was observed in 21 women (-3.1+/-2.1
      mm) in late gestation, whereas 18 women had an increase (4.3+/-3.2 mm), P<0.001.
      The group of women who lost body fat (decrease in skinfold thickness) had a trend
      toward greater pregravid body mass index (BMI, 25 vs 22 kg/m(2), P=0.06), and
      gained less weight in late gestation (3.0 vs 4.3 kg, P=0.042). On multiple
      regression, maternal age and gestational weight gain were positively correlated
      with fat mass accrual, whereas pregravid BMI and dietary fiber were negative
      determinants of late gestational fat mass. CONCLUSION: Increases in maternal fat
      mass in late gestation were related to maternal age and gestational weight gain,
      whereas decreases were related to increased pregravid BMI and dietary fiber.

PMID- 24030675
TI  - Estimating the nucleated red blood cell 'emergence time' in neonates.
AB  - OBJECTIVE: The time between onset of fetal hypoxia and first appearance of
      nucleated red blood cells (NRBCs) in the blood can conceptually be divided into
      two periods; (1) the 'erythropoietin (EPO) generation time', which previous fetal
      studies suggest is 4 to 5 h, and (2) the 'NRBC emergence time'. In this study, we
      estimated the latter as the time required for NRBC to appear in the blood after
      administering a dose of recombinant EPO. STUDY DESIGN: This was a retrospective
      analysis of data from a multihospital healthcare system (Intermountain
      Healthcare). Data were included only for neonates born >=34 weeks gestation
      between the dates 1 January 2005 and 31 October 2012 and only if they received a
      dose of darbepoetin during their neonatal intensive care unit stay and had one or
      more complete blood cell counts (CBCs) obtained during the 3-day period before
      the dose was given and one or more CBCs in the 7-day period after the dose.
      RESULT: The study involved 31 neonates who received 34 doses of darbepoetin.
      Seven doses were 4 MUg kg(-1) and twenty-seven doses were 10 MUg kg(-1). Twenty
      six CBCs were obtained during the 24-h period following the darbepoetin dose and
      none had NRBC identified. NRBC first appeared in the blood between 24 and 36 h
      after the dose. Recipients of the higher dose generally had a higher peak NRBC
      count but the NRBC 'emergence time' did not appear to depend on dose. CONCLUSION:
      Following fetal hypoxia, transcription and translation of the EPO gene result in
      an elevation in plasma EPO concentration. Previous fetal studies suggest this
      process requires 4 to 5 h. The present studies suggest that, following the
      increase in plasma EPO, NRBC emerge into the circulation in >=24 h. If this model
      serves as a reasonable estimate, it suggests that neonates with an elevated NRBC
      count at birth had the onset of hypoxia at least 28 to 29 h before birth.

PMID- 24030676
TI  - Late-onset neutropenia: defining limits of neutrophil count in very low birth
      weight infants.
AB  - OBJECTIVE: To evaluate the incidence, onset, duration, characteristics and
      importance of late-onset neutropenia (defined as absolute neutrophil count<1500
      MUl(-1) at 3 weeks of age or later) in a group of very low birth weight (VLBW)
      infants. STUDY DESIGN: Routine complete blood cell counts (CBCs) obtained from
      VLBW infants over a period of 7 years were gathered retrospectively, including
      those of newborns with weekly CBCs taken over a duration of at least 3 weeks.
      Data were obtained from between January 2003 and December 2009. RESULT: CBCs of
      399 newborns were included. Values were obtained from birth to 36 weeks of
      postnatal age. Late-onset neutropenia was observed in 259 cases (65%).
      Neutropenic infants had a mean of 0.5 weeks lower gestational age. Late-onset
      neutropenia was more frequent in children with intraventricular hemorrhage but
      not in patients who received erythropoietin. The median age of neutropenia onset
      was 7 weeks in extremely low birth weight infants and 6 weeks in VLBW infants.
      The fifth percentile of neutrophils between weeks 3 and 4 was 1280 MUl(-1) and
      between weeks 13 and 15 was 500 MUl(-1). The average duration was 2 weeks with
      normalized values after 18 weeks. CONCLUSION: A neutrophil count <1500 MUl(-1)
      after the third week of life is frequently observed in VLBW infants and should
      not be used as a lower reference limit. The fifth percentile varies according to
      postnatal age from around 1300 MUl(-1) in week 4 of life, decreasing to a nadir
      of 500 MUl(-1) between 3 and 4 months of age. Values normalize in the first year
      of life.

PMID- 24030678
TI  - Metalation dictates remote regioselectivity: ruthenium-catalyzed
      functionalization of meta C(Ar)-H Bonds.
AB  - Remote control: The title reaction is effective for the sulfonation and
      alkylation of arenes bearing directing groups. Initial ortho metalation of the
      substrate forms an intermediate which does not evolve towards functionalization
      at the C?M bond. Instead, the ruthenium catalyst acts as a strong electron
      donating group, thus directing a remote electrophilic attack. 

PMID- 24030677
TI  - Whole-blood viscosity in the neonate: effects of gestational age, hematocrit,
      mean corpuscular volume and umbilical cord milking.
AB  - OBJECTIVE: The American College of Obstetrics and Gynecology Committee on
      Obstetric Practice recently endorsed delayed cord clamping at preterm delivery.
      However, the committee report expressed the concern by some practitioners that
      delayed clamping or cord milking might induce hyperviscosity in preterm neonates.
      To address this issue we: (1) established reference ranges for whole-blood
      viscosity among preterm neonates (viscosity reference ranges had previously been
      reported only in term neonates) and (2) determined the effect of umbilical cord
      milking at deliveries <32 weeks gestation on subsequent blood viscosity
      measurements. STUDY DESIGN: This was a prospective study in two Neonatal
      Intensive Care Units. Blood viscosity was measured using a cone and plate
      viscometer. Associations were sought with gestation, hematocrit/hemoglobin and
      mean corpuscular volume. Reference ranges were determined for preterm infants <32
      weeks gestation. Then, after umbilical cord milking at deliveries <32 weeks,
      viscosity was measured at birth and again during the 12 h after birth. In
      neonates with viscosities >95th % range, we sought signs of hyperviscosity
      (plethora, hypotonia, hypoglycemia, hyperbilirubinemia, thrombocytopenia).
      RESULT: Viscosity at higher and lower sheer rates were linearly related (n=32,
      r=0.971). Within the range of hematocrits measured (29-63%) viscosity correlated
      with hematocrit (r=0.877) and hemoglobin (r=0.853) but not with erythrocyte size
      (r=0.179). Viscosity was related to gestational age (n=58), primarily due to the
      lower hematocrits at lower gestational ages. In the 12 h after cord milking
      viscosity ranged from 3.1 to 9.5 centipoise. Three of twenty preterm, neonates
      had viscosities >95th % reference range. However, all values were well below
      those where hyperviscosity is defined in term neonates and all lacked features of
      hyperviscosity. CONCLUSION: Cord blood viscosity is directly proportional to
      hematocrit/hemoglobin, lower at early gestation and not associated with
      erythrocyte size. Cord milking at preterm delivery is associated with a low risk
      of clinical hyperviscosity. Practioners should not refrain from cord milking at
      preterm delivery because of a concern that it will commonly cause neonatal
      hyperviscosity.

PMID- 24030680
TI  - Portable nucleic acid thermocyclers.
AB  - A nucleic acid thermal cycler is considered to be portable if it is under ten
      pounds, easily carried by one individual, and battery powered. Nucleic acid
      amplification includes both polymerase chain reaction (e.g. PCR, RT-PCR) and
      isothermal amplification (e.g. RPA, HDA, LAMP, NASBA, RCA, ICAN, SMART, SDA).
      There are valuable applications for portable nucleic acid thermocyclers in fields
      that include clinical diagnostics, biothreat detection, and veterinary testing. A
      system that is portable allows for the distributed detection of targets at the
      point of care and a reduction of the time from sample to answer. The designer of
      a portable nucleic acid thermocycler must carefully consider both thermal control
      and the detection of amplification. In addition to thermal control and detection,
      the designer may consider the integration of a sample preparation subsystem with
      the nucleic acid thermocycler. There are a variety of technologies that can
      achieve accurate thermal control and the detection of nucleic acid amplification.
      Important evaluation criteria for each technology include maturity, power
      requirements, cost, sensitivity, speed, and manufacturability. Ultimately the
      needs of a particular market will lead to user requirements that drive the
      decision between available technologies. 

PMID- 24030679
TI  - What are we missing? The costs versus benefits of skip rule designs.
AB  - Many research diagnostic interviews employ skip rules, such that some questions
      are only asked based on answers to prior questions. In the context of large-scale
      epidemiological studies, skip rules are important to study feasibility by
      reducing the time, money, and participant burden required for assessment.
      However, less is understood about information lost when questions are skipped.
      This study examines the relative prevalence, clinical significance, and
      additional time required to assess eating disorder symptom patterns skipped in
      the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to
      understand the costs and benefits of following skip rules. Data come from the
      second stage of a two-stage cohort sample (N = 400) in which the SCID-I eating
      disorders module was administered without following skip rules. Results were
      weighted to correct for the sampling framework. Over a third of subjects endorsed
      symptoms that would have been missed had skip rules been followed. Uncaptured
      symptom patterns were associated with increased psychosocial impairment, and the
      additional time required to assess all symptoms averaged 1.8 minutes per
      participant. Clinically significant symptom patterns are missed by the SCID-I and
      similar diagnostic tools, suggesting that epidemiologic studies using such
      instruments under-estimate the prevalence and public health impact of mental
      disorders.

PMID- 24030681
TI  - A self-sensing active magnetic bearing based on a direct current measurement
      approach.
AB  - Active magnetic bearings (AMBs) have become a key technology in various
      industrial applications. Self-sensing AMBs provide an integrated sensorless
      solution for position estimation, consolidating the sensing and actuating
      functions into a single electromagnetic transducer. The approach aims to reduce
      possible hardware failure points, production costs, and system complexity.
      Despite these advantages, self-sensing methods must address various technical
      challenges to maximize the performance thereof. This paper presents the direct
      current measurement (DCM) approach for self-sensing AMBs, denoting the direct
      measurement of the current ripple component. In AMB systems, switching power
      amplifiers (PAs) modulate the rotor position information onto the current
      waveform. Demodulation self-sensing techniques then use bandpass and lowpass
      filters to estimate the rotor position from the voltage and current signals.
      However, the additional phase-shift introduced by these filters results in lower
      stability margins. The DCM approach utilizes a novel PA switching method that
      directly measures the current ripple to obtain duty-cycle invariant position
      estimates. Demodulation filters are largely excluded to minimize additional phase
      shift in the position estimates. Basic functionality and performance of the
      proposed self-sensing approach are demonstrated via a transient simulation model
      as well as a high current (10 A) experimental system. A digital implementation of
      amplitude modulation self-sensing serves as a comparative estimator. 

PMID- 24030682
TI  - Temperature stability of the sky quality meter.
AB  - The stability of radiance measurements taken by the Sky Quality Meter (SQM)was
      tested under rapidly changing temperature conditions during exposure to a stable
      light field in the laboratory. The reported radiance was found to be negatively
      correlated with temperature, but remained within 7% of the initial reported
      radiance over a temperature range of -15  degrees C to 35  degrees C, and during
      temperature changes of -33  degrees C/h and +70  degrees C/h.This is smaller than
      the manufacturer's quoted unit-to-unit systematic uncertainty of 10%,indicating
      that the temperature compensation of the SQM is adequate under expected outdoor
      operating conditions.

PMID- 24030683
TI  - Determination of the elastic properties of tomato fruit cells with an atomic
      force microscope.
AB  - Since the mechanical properties of single cells together with the intercellular
      adhesive properties determine the macro-mechanical properties of plants, a method
      for evaluation of the cell elastic properties is needed to help explanation of
      the behavior of fruits and vegetables in handling and food processing. For this
      purpose, indentation of tomato mesocarp cells with an atomic force microscope was
      used. The Young's modulus of a cell using the Hertz and Sneddon models, and
      stiffness were calculated from force-indentation curves. Use of two probes of
      distinct radius of curvature (20 nm and 10,000 nm) showed that the measured
      elastic properties were significantly affected by tip geometry. The Young's
      modulus was about 100 kPa +/- 35 kPa and 20 kPa +/- 14 kPa for the sharper tip
      and a bead tip, respectively. Moreover, large variability regarding elastic
      properties (>100%) among cells sampled from the same region in the fruit was
      observed. We showed that AFM provides the possibility of combining nano
      mechanical properties with topography imaging, which could be very useful for the
      study of structure-related properties of fruits and vegetables at the cellular
      and sub-cellular scale. 

PMID- 24030684
TI  - Lack of association between GRIA1 polymorphisms and haplotypes with migraine
      without aura or response to triptans.
AB  - The present study was designed to replicate previous findings reporting a
      significant association between the rs548294 polymorphism at the glutamate
      receptor subunit GluR1 gene (GRIA1) and migraine without aura, either as a single
      marker or in haplotype combination with rs2195450. In addition, the role of GRIA1
      polymorphisms and haplotypes was evaluated in migraine patients without aura as
      predictive factors for consistency in headache response to triptans. Analysis of
      rs548294 and rs2195450 polymorphisms of GRIA1 was conducted by Real-time PCR
      allelic discrimination assay in 186 migraine patients without aura and 312
      healthy controls, respectively. In the logistic regression analysis adjusted for
      gender and age, genotype and haplotype frequencies for the two polymorphisms did
      not significantly differ between migraine patients without aura and controls. In
      addition, no evidence of association was found between GRIA1
      polymorphisms/haplotypes and consistent response to triptans. This study failed
      to replicate previously reported association between GRIA1 rs548294 and migraine
      without aura, either as single marker or when analyzed in haplotype combination
      with rs2195450. In addition, no evidence was found for a relevant role of GRIA1
      polymorphisms and haplotypes as modulating factors of headache response to
      triptans.

PMID- 24030685
TI  - A prospective, open-label study of milnacipran in the prevention of headache in
      patients with episodic or chronic migraine.
AB  - Migraine is a highly prevalent episodic and chronic neurological disorder that
      impacts otherwise healthy men and women in their most productive years. An
      anecdotal survey in our clinical practices suggested that milnacipran, a drug
      indicated for the treatment of fibromyalgia, reduced the incidence of headache in
      patients with migraine. In this 3-month, open-label, pilot study, 38 patients
      diagnosed with episodic migraine and 7 patients with chronic migraine maintained
      headache diaries to assess the effectiveness and tolerability of milnacipran in
      headache prevention. After a 1-month period to obtain baseline data, milnacipran
      treatment was initiated and doses were titrated up to 100 mg/day over 1 month.
      Maintenance therapy continued for an additional 3 months. The primary efficacy
      end point was change from baseline in the number of all headache days during the
      last 28 days of maintenance therapy analyzed, using last observation carried
      forward (LOCF). Change from baseline in migraine days during the last month of
      the maintenance period using LOCF was a secondary end point. Milnacipran 100 mg
      daily was associated with a significant reduction in headache (-4.2 days; P <
      0.001) and migraine frequency (-2.2 days; P < 0.003). The adverse event profile
      was consistent with prior reports of milnacipran for the treatment of other
      conditions. However, compared with the recommended protocol, a more gradual
      increase in milnacipran dose was required to improve tolerability for some
      patients. The robust efficacy signal found in this study strongly suggests that a
      double-blind, placebo-controlled trial of milnacipran in migraine and chronic
      headache is warranted.

PMID- 24030686
TI  - Lack of association of BRAF mutation with negative prognostic indicators in
      papillary thyroid carcinoma: the University of California, San Francisco,
      experience.
AB  - IMPORTANCE: Papillary thyroid carcinoma (PTC) is the most common endocrine
      neoplasm. B-type raf kinase (BRAF) V600E mutation has been proposed as a negative
      prognostic indicator in PTC, and patients harboring it should receive more
      aggressive initial therapy. OBJECTIVE: To assess the significance of BRAF V600E
      mutation in PTC in the largest US sample to date. DESIGN: We identified patients
      from our institution's pathology archives diagnosed as having PTC and meeting
      criteria for BRAF mutation testing. Medical records were analyzed for BRAF status
      (positive or negative) and a list of standardized clinicopathologic features.
      PARTICIPANTS: A total of 429 patients with PTC at an academic medical center.
      MAIN OUTCOMES AND MEASURES: Clinicopathologic features in patients with PTC with
      and without BRAF mutation. RESULTS: Of 429 cases with PTC, 314 (73.2%) were
      positive for the BRAF mutation and 115 (26.8%) tested negative. BRAF mutation was
      significantly associated with tumor margin positivity (P = .03) and lymph node
      metastasis (P = .002) on univariate analysis but not on multivariate study. BRAF
      mutation was a predictor of male sex (odds ratio [OR], 3.2; 95% CI, 1.4-7.2),
      total thyroidectomy (OR, 2.6; 95% CI, 1.1-6.2), and a negative predictor of
      follicular variant PTC (OR, 0.1; 95% CI, 0.1-0.4). There was no significant
      association between BRAF positivity and tumor multicentricity, lymphovascular
      invasion, extranodal extension, central neck involvement, advanced stage (stage
      III or IV), and distant metastasis. CONCLUSIONS AND RELEVANCE: BRAF V600E
      mutation has been extensively studied in relation to negative prognostic
      indicators in PTC, with no consistent relationship emerging. Two recent meta
      analyses showed an overall association between BRAF status and aggressive disease
      features and called for tailoring treatment plans in patients accordingly. In
      this, the largest US study to date, BRAF status was not significantly associated
      with most clinicopathologic features suggestive of more aggressive disease.

PMID- 24030688
TI  - Halomonas olivaria sp. nov., a moderately halophilic bacterium isolated from
      olive-processing effluents.
AB  - A moderately halophilic, Gram-stain-negative, non-sporulating bacterium designed
      as strain TYRC17(T) was isolated from olive-processing effluents. The organism
      was a straight rod, motile by means of peritrichous flagella and able to respire
      both oxygen and nitrate. Growth occurred with 0-25 % (w/v) NaCl (optimum, 7 %),
      at pH 5-11 (optimum, pH 7.0) and at 4-50  degrees C (optimally at 35  degrees C).
      It accumulated poly-beta-hydroxyalkanoate granules and produced
      exopolysaccharides. The predominant fatty acids were C18 : 1omega7c, C16 :
      1omega7c and C16 : 0. Ubiquinone 9 (Q-9) was the only respiratory quinone. The
      DNA G+C content of TYRC17(T) was 53.9 mol%. Phylogenetic analyses of 16S rRNA
      gene sequences revealed that the strain represents a member of the genus
      Halomonas and more precisely of the subgroup containing Halomonas sulfidaeris, H.
      titanicae, H. variabilis, H. zhanjiangensis, H. alkaliantarctica, H. boliviensis
      and H. neptunia. TYRC17(T) showed high 16S-rRNA sequence identities in particular
      with the three last species listed (99.4-99.5 %). A multilocus sequence analysis
      (MLSA) using the 23S rRNA, gyrB, rpoD and secA genes allowed clarifying the
      phylogenetic position of TYRC17(T). This, combined with the level of DNA-DNA
      hybridization between TYRC17(T) and its closest relatives ranging from 21.6 % to
      48.4 %, indicated that TYRC17(T) did not represent any of these species. On the
      basis of phenotypic and genotypic characteristics, and also genomic and
      phylogenetic evidence, it was concluded that strain TYRC17(T) represented a novel
      species of the genus Halomonas. The name Halomonas olivaria sp. nov. is proposed
      with TYRC17(T) ( = DSM 19074(T) = CCUG 53850B(T)) as the type strain. 

PMID- 24030687
TI  - Low-level laser therapy for spinal cord injury in rats: effects of polarization.
AB  - The effects of laser polarization on the efficacy of near-infrared low-level
      laser therapy for spinal cord injury (SCI) are presented. Rat spinal cords were
      injured with a weight-drop device, and the lesion sites were directly irradiated
      with a linearly polarized 808-nm diode laser positioned either perpendicular or
      parallel to the spine immediately after the injury and daily for five consecutive
      days. Functional recovery was assessed daily by an open-field test. Regardless of
      the polarization direction, functional scores of SCI rats that were treated with
      the 808-nm laser irradiation were significantly higher than those of SCI alone
      group (Group 1) from day 5 after injury. The locomotive function of SCI rats
      irradiated parallel to the spinal column (Group 3) was significantly improved
      from day 10 after injury, compared to SCI rats treated with the linear
      polarization perpendicular to the spinal column (Group 2). There were no
      significant differences in ATP contents in the injured tissue among the three
      groups. We speculate that the higher efficacy with parallel irradiation is
      attributable to the deeper light penetration into tissue with anisotropic
      scattering.

PMID- 24030689
TI  - Altererythrobacter atlanticus sp. nov., isolated from deep-sea sediment.
AB  - A Gram-stain-negative, short rod-shaped bacterium, designated 26DY36(T), was
      isolated from a deep-sea sediment sample collected from the North Atlantic Rise.
      The isolate required NaCl and grew best with 2 % (w/v) sea salts at a temperature
      of 30-35  degrees C and at pH 7.0. It formed yellow colonies, produced carotenoid
      like pigments and did not produce bacteriochlorophyll a. Strain 26DY36(T) was
      positive for hydrolysis of aesculin, gelatin, tyrosine and Tweens 20, 40, 60 and
      80, but negative for hydrolysis of casein, DNA and starch. The major respiratory
      quinone was ubiquinone-10. The major polar lipid profile consisted of
      sphingoglycolipid, diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylcholine and two unidentified glycolipids. The
      principal fatty acids (>5 %) were C18 : 1omega7c, C17 : 1omega6c, C15 : 0 2-OH
      and C16 : 0. The genomic DNA G+C content was 59.4 mol%. Phylogenetic analysis
      based on the 16S rRNA gene sequences indicated that strain 26DY36(T) should be
      assigned to the genus Altererythrobacter. 16S rRNA gene sequence similarities
      between the isolate and the type strains of species of the genus
      Altererythrobacter were in the range 92.7-96.5 %. On the basis of phenotypic and
      genotypic data, strain 26DY36(T) represents a novel species of the genus
      Altererythrobacter, for which the name Altererythrobacter atlanticus sp. nov.
      (type strain, 26DY36(T) = CGMCC 1.12411(T) = JCM 18865(T)) is proposed. 

PMID- 24030690
TI  - Aquimarina megaterium sp. nov., isolated from seawater.
AB  - A novel Gram-stain-negative, rod-shaped, non-flagellated, strictly aerobic strain
      with gliding motility, designated XH134(T), was isolated from surface seawater of
      the South Pacific Gyre (45 degrees  58' S 163 degrees  11' W) during the
      Integrated Ocean Drilling Program Expedition 329. The major respiratory quinone
      of strain XH134(T) was MK-6. The dominant fatty acids of strain XH134(T) were iso
      C15 : 0, iso-C15 : 1 G, C16 : 1omega6c and/or C16 : 1omega7c, iso-C17 : 0 3-OH,
      iso-C15 : 0 3-OH and 10-methyl C16 : 0 and/or iso-C17 : 1omega9c. The polar
      lipids of strain XH134(T) comprised phosphatidylethanolamine, one unknown
      aminolipid and three unknown polar lipids. The DNA G+C content of strain XH134(T)
      was 32.4 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that
      the novel strain was related most closely to Aquimarina macrocephali JAMB N27(T)
      with 96.9 % sequence similarity. A number of phenotypic characteristics
      distinguished strain XH134(T) from described members of the genus Aquimarina. On
      the basis of combined phenotypic and phylogenetic analyses, strain XH134(T)
      represents a novel species of the genus Aquimarina, for which the name Aquimarina
      megaterium sp. nov. is proposed. The type strain is XH134(T) ( = CGMCC 1.12186(T)
      = JCM 18215(T)). 

PMID- 24030691
TI  - Massilia umbonata sp. nov., able to accumulate poly-beta-hydroxybutyrate,
      isolated from a sewage sludge compost-soil microcosm.
AB  - A bacterial strain, designated strain LP01(T), was isolated from a laboratory
      scale microcosm packed with a mixture of soil and sewage sludge compost designed
      to study the evolution of microbial biodiversity over time. The bacterial strain
      was selected for its potential ability to store polyhydroxyalkanoates (PHAs) as
      intracellular granules. The cells were aerobic, Gram-stain-negative, non
      endospore-forming motile rods. Phylogenetically, the strain was classified within
      the genus Massilia, as its 16S rRNA gene sequence had similarity of 99.2 % with
      respect to those of Massilia albidiflava DSM 17472(T) and M. lutea DSM 17473(T).
      DNA-DNA hybridization showed low relatedness of strain LP01(T) to the type
      strains of other, phylogenetically related species of the genus Massilia. It
      contained Q-8 as the predominant ubiquinone and summed feature 3 (C16 : 1omega7c
      and/or iso-C15 : 0 2-OH) as the major fatty acid(s). It was found to contain
      small amounts of the fatty acids C18 : 0 and C14 : 0 2-OH, a feature that served
      to distinguish it from its closest phylogenetic relatives within the genus
      Massilia. The DNA G+C content was 66.0 mol%. Phylogenetic, phenotypic and
      chemotaxonomic data obtained in this study suggest that strain LP01(T) represents
      a novel species of the genus Massilia, for which the name Massilia umbonata sp.
      nov. is proposed. The type strain is LP01(T) ( = CECT 7753(T) = DSM 26121(T)). 

PMID- 24030692
TI  - Replantation: the 50th year.

PMID- 24030693
TI  - Catalytic cross deoxygenative and dehydrogenative coupling of aldehydes and
      alkenes: a redox-neutral process to produce skipped dienes.
AB  - A novel catalytic cross deoxygenative and dehydrogenative coupling reaction of
      aldehydes and alkenes was established via a cooperative catalysis approach. This
      transformation provided an efficient and atom-economic protocol for the synthesis
      of 1,4-skipped dienes from aldehydes and simple alkenes under oxidant-free
      reaction conditions. 

PMID- 24030694
TI  - Obesity modifies expression profiles of metabolic markers in superficial and deep
      subcutaneous abdominal adipose tissue depots.
AB  - While visceral adipose tissue (VAT) associates to obesity, there is debate for
      subcutaneous adipose tissue (SAT). One explanation may be SAT subcompartments,
      superficial-SAT (sSAT) and deep-SAT (dSAT), recently recognized as independent
      depots. Our aim was to establish roles for sSAT/dSAT with obesity by examining
      the expression of proteins key to adipocyte metabolism. Paired biopsies from sSAT
      and dSAT of 10 normal-weight (BMI 21.8 +/- 0.8 kg/m(2)) and 11 obese subjects
      (BMI 44 +/- 2.1 kg/m(2)) were analyzed for differences in insulin sensitivity
      using adiponectin, GLUT4 and resistin, glucocorticoid metabolism by 11betaHSD1
      and alterations of the adipokines leptin and TNFalpha. Between lean and obese
      subjects, sSAT and dSAT changes for GLUT4, resistin and TNFalpha were equivalent.
      Resistin and TNFalpha increased in both obese SAT sub-compartments; 33-fold
      (sSAT; P < 0.006) and 18.5-fold (dSAT; P < 0.003) higher resistin, with
      undetectable in leans to significant TNFalpha levels in obese. In contrast, GLUT4
      showed 5.5-fold (sSAT; P < 0.03) and 7-fold (dSAT; P < 0.03) lower levels in
      obese, correlating to BMI (r = -0.6423, P = 0.007) and HOMA-IR (r = -0.5882, P =
      0.017). Exclusive sSAT-specific differences were observed for adiponectin,
      leptin, and 11betaHSD1. Both sSAT 11betaHSD1 and leptin increased in obese, with
      11betaHSD1 2.5-fold (P = 0.052) and leptin 3.3-fold (P < 0.008) higher, with
      11betaHSD1 correlating to HOMA-IR (r = 0.5203, P = 0.0323) and leptin to BMI (r =
      0.5810, P = 0.01). In contrast, obese had 7-fold (P < 0.02) lower sSAT
      adiponectin, correlating to BMI (r = -0.5178, P = 0.027) and HOMA-IR (r = 
      0.4570, P = 0.049). Overall, sSAT and dSAT are distinct abdominal adipose tissue
      depots with independent metabolic functions. Between the two, sSAT shows clear
      independent effects that associate to obesity and its metabolic complications.

PMID- 24030695
TI  - Glycemic variability in normal glucose regulation subjects with elevated 1-h
      postload plasma glucose levels.
AB  - Subjects with normal glucose regulation (NGR), whose 1-h postload plasma glucose
      is >=8.6 mmol/L (155 mg/dL, NGR 1 h >= 8.6) during 75-g oral glucose tolerance
      test (OGTT), have an increased risk of type 2 diabetes and subclinical organ
      damage. And, the deficiency in islet beta cell function is responsible for
      glycemic disorders. The purpose of this study is to investigate glycemic
      variability in NGR subjects with elevated 1-h postload plasma glucose levels and
      its association with islet beta cell function. The 29 NGR subjects with 1-h
      postload plasma glucose >=8.6 mmol/L (NGR 1 h >= 8.6) and 29 age- and sex-matched
      NGR subjects with 1-h postload plasma glucose <8.6 mmol/L (NGR 1 h < 8.6) were
      recruited in the study. Insulin sensitivity (Matsuda index, ISI), insulin
      secretion (insulinogenic index DeltaI30/DeltaG30), and integrated beta cell
      function measured by the oral disposition index (DeltaI30/DeltaG30 multiplied by
      the ISI) were derived from OGTT. All subjects were monitored using the continuous
      glucose monitoring system for consecutive 72 h. The multiple parameters of
      glycemic variability included the standard deviation of blood glucose (SDBG),
      mean blood glucose (MBG), mean of daily differences (MODD), and mean amplitude of
      glycemic excursions (MAGE). MAGE is considered as a gold standard of glycemic
      variability. Glycemic variability parameters SDBG, MBG, MODD, and MAGE in NGR 1 h
      >= 8.6 group were higher than those in NGR 1 h < 8.6 group (p < 0.05), and oral
      disposition index in NGR 1 h >= 8.6 group was lower than that in NGR 1 h < 8.6
      group (p < 0.05). SDBG, MBG, MODD, MAGE, and 1-h postload plasma glucose all
      negatively associated with oral disposition index in the separate group (p <
      0.05) and in the whole subjects (p < 0.05). After multivariate regression
      analysis, oral disposition index was the strongest independent contributor to
      MAGE and 1-h postload plasma glucose in the separate group (p < 0.05) and in the
      whole subjects (p < 0.05). It is concluded that NGR 1 h >= 8.6 group had higher
      glycemic variability and lower oral disposition index, compared with NGR 1 h <
      8.6 group. Increased glycemic variability parameters and elevated 1-h postload
      plasma glucose consistently associated with declined oral disposition index in
      subjects from NGR 1 h < 8.6 to NGR 1 h >= 8.6 group.

PMID- 24030696
TI  - Traumatic brain injury: endocrine consequences in children and adults.
AB  - Traumatic brain injury (TBI) is a common cause of death and disability in young
      adults with consequences ranging from physical disabilities to long-term
      cognitive, behavioral, psychological and social defects. Recent data suggest that
      pituitary hormone deficiency is not infrequent among TBI survivors; the
      prevalence of reported hypopituitarism following TBI varies widely among
      published studies. The most common cause of TBI is motor vehicle accidents,
      including pedestrian-car and bicycle car encounters, falls, child abuse, violence
      and sports injuries. Prevalence of hypopituitarism, from total to isolated
      pituitary deficiency, ranges from 5 to 90 %. The time interval between TBI and
      pituitary function evaluation is one of the major factors responsible for
      variations in the prevalence of hypopituitarism reported. Endocrine dysfunction
      after TBI in children and adolescents is common. Adolescence is a time of growth,
      freedom and adjustment, consequently TBI is also common in this group. Sports
      related TBI is an important public health concern, but many cases are
      unrecognized and unreported. Sports that are associated with an increased risk of
      TBI include those involving contact and/or collisions such as boxing, football,
      soccer, ice hockey, rugby, and the martial arts, as well as high velocity sports
      such as cycling, motor racing, equestrian sports, skiing and roller skating. The
      aim of this paper is to summarize the best evidence of TBI as a cause of
      pituitary deficiency in children and adults.

PMID- 24030697
TI  - Effect of interface on mechanical properties and biodegradation of PCL HAp
      supramolecular nano-composites.
AB  - This research explores the correlation between the structural properties of
      supramolecular biocomposites and their mechanical strength. Hybrid biocomposites
      composed of surface-modified hydroxyapatite nano-particles and supramolecular
      polycaprolactone (SP PCL), were prepared at different compositions, and their
      mechanical, thermal and viscoelastic properties as well as biodegradability,
      biocompatibility and cytotoxicity were evaluated in vitro. The results were
      compared with those for SP PCL/naked hydroxyapatite nano-composites. We show that
      surface modification of hydroxyapatite nanoparticles resulted in outstanding
      improvement of tensile strength and modulus up to 3.6 and 2.2-fold, respectively.
      At above 10 wt% HAp and 20 wt% HApUPy, heterogeneous nano-composites with
      inferior mechanical properties were obtained. Based on rheological (in steady
      shear mode) and small/wide angle X-ray scattering measurements, unusual improved
      mechanical properties were ascribed to the formation of supramolecular clusters
      around nanoparticles. In-vitro degradation of the supramolecular nano-composites
      was also studied to investigate the overall product biodegradation as well as
      toxicity of the degradation product(s).

PMID- 24030699
TI  - Patient transfers and assistive devices: prospective cohort study on the risk for
      occupational back injury among healthcare workers.
AB  - OBJECTIVES: This prospective cohort study investigates work-related risk factors
      for occupational back injury among healthcare workers. METHODS: The study
      comprised 5017 female healthcare workers in eldercare from 36 municipalities in
      Denmark who responded to a baseline and follow-up questionnaire in 2005 and 2006,
      respectively. Using logistic regression, the odds for occupational back injury
      (ie, sudden onset episodes) in 2006 from patient transfers in 2005 was modeled.
      RESULTS: In the total study population, 3.9% experienced back injury during
      follow-up, of which 0.5% were recurrent events. When adjusting for lifestyle
      (body mass index, leisure-time physical activity, smoking), work-related
      characteristics (seniority and perceived influence at work), and history of back
      pain and injury, daily patient transfers increased the risk for back injury
      (trend, P=0.03): odds ratio (OR) 1.75 [95% confidence interval (95% CI) 1.05
      2.93] for 1-2 transfers per day, OR 1.81 (95% CI 1.14-2.85) for 3-10 transfers
      per day, and OR 1.56 (95% CI 0.96-2.54) for >10 transfers per day, referencing
      those with <1 patient transfer on average per day. The population attributable
      fraction of daily patient transfer for back injury was estimated to be 36%. Among
      those with daily patient transfer (N=3820), using an assistive device decreased
      the risk for back injury for "often" and "very often" use [OR 0.59 (95% CI 0.36
      0.98) and OR 0.62 (95% CI 0.38-1.00), respectively] referencing those who
      "seldom" use assistive devices. CONCLUSION: Daily patient transfer was associated
      with increased risk for back injury among healthcare workers. Persistent use of
      an assistive device was associated with reduced risk for back injury among
      healthcare workers with daily patient transfers.

PMID- 24030698
TI  - Super-paramagnetic responsive nanofibrous scaffolds under static magnetic field
      enhance osteogenesis for bone repair in vivo.
AB  - A novel nanofibrous composite scaffold composed of super-paramagnetic gamma-Fe2O3
      nanoparticles (MNP), hydroxyapatite nanoparticles (nHA) and poly lactide acid
      (PLA) was prepared using electrospinning technique. The scaffold well responds
      extern static magnetic field with typical saturation magnetization value of 0.049
      emu/g as well as possesses nanofibrous architecture. The scaffolds were implanted
      in white rabbit model of lumbar transverse defects. Permanent magnets are fixed
      in the rabbit cages to provide static magnetic field for the rabbits post
      surgery. Results show that MNP incorporated in the nanofibers endows the
      scaffolds super-paramagnetic responsive under the applied static magnetic field,
      which accelerates new bone tissue formation and remodeling in the rabbit defect.
      The scaffold also exhibits good compatibility of CK, Cr, ALT and ALP within
      normal limits in the serum within 110 days post implantation. In conclusion, the
      super-paramagnetic responding scaffold with applying of external magnetic field
      provides a novel strategy for scaffold-guided bone repair. 

PMID- 24030700
TI  - Topology, chirality and interpenetration in coordination polymers.
AB  - This Viewpoint turns back the clock to 1998 when a contribution by Carlucci,
      Ciani, Macchi and Proserpio (Chem. Commun., 1998, 1837-1838) addressed the
      existence of multiple properties in coordination polymer networks and the use of
      topology for classifying network connectivity, thereby serving as a presage of
      the exponential growth in the field of coordination polymers that continues
      unabated to this day. 

PMID- 24030701
TI  - The mTOR kinase inhibitors, CC214-1 and CC214-2, preferentially block the growth
      of EGFRvIII-activated glioblastomas.
AB  - PURPOSE: mTOR pathway hyperactivation occurs in approximately 90% of
      glioblastomas, but the allosteric mTOR inhibitor rapamycin has failed in the
      clinic. Here, we examine the efficacy of the newly discovered ATP-competitive
      mTOR kinase inhibitors CC214-1 and CC214-2 in glioblastoma, identifying molecular
      determinants of response and mechanisms of resistance, and develop a
      pharmacologic strategy to overcome it. EXPERIMENTAL DESIGN: We conducted in vitro
      and in vivo studies in glioblastoma cell lines and an intracranial model to:
      determine the potential efficacy of the recently reported mTOR kinase inhibitors
      CC214-1 (in vitro use) and CC214-2 (in vivo use) at inhibiting rapamycin
      resistant signaling and blocking glioblastoma growth and a novel single-cell
      technology-DNA Encoded Antibody Libraries-was used to identify mechanisms of
      resistance. RESULTS: Here, we show that CC214-1 and CC214-2 suppress rapamycin
      resistant mTORC1 signaling, block mTORC2 signaling, and significantly inhibit the
      growth of glioblastomas in vitro and in vivo. EGFRvIII expression and PTEN loss
      enhance sensitivity to CC214 compounds, consistent with enhanced efficacy in
      strongly mTOR-activated tumors. Importantly, CC214 compounds potently induce
      autophagy, preventing tumor cell death. Genetic or pharmacologic inhibition of
      autophagy greatly sensitizes glioblastoma cells and orthotopic xenografts to
      CC214-1- and CC214-2-induced cell death. CONCLUSIONS: These results identify
      CC214-1 and CC214-2 as potentially efficacious mTOR kinase inhibitors in
      glioblastoma, and suggest a strategy for identifying patients most likely to
      benefit from mTOR inhibition. In addition, this study also shows a central role
      for autophagy in preventing mTOR-kinase inhibitor-mediated tumor cell death, and
      suggests a pharmacologic strategy for overcoming it.

PMID- 24030702
TI  - Hepatocellular carcinoma from an immunologic perspective.
AB  - Hepatocellular carcinoma is the third most common cancer worldwide. It is an
      inflammation-associated cancer. Multiple investigators have demonstrated that
      analysis of the tumor microenvironment may be used to predict patient outcome,
      indicating the importance of local immune responses in this disease. In contrast
      with other types of cancer, in which surgery, radiation, and systemic cytotoxic
      chemotherapies dominate the treatment options, in hepatocellular carcinoma
      locoregional treatments are widely applied. Such treatments induce rapid tumor
      cell death and antitumor immune responses, which may favor or impair the
      patients' outcome. Recent immunotherapeutic studies demonstrating promising
      results include trials evaluating intratumoral injection of an oncolytic virus
      expressing granulocyte macrophage colony-stimulating factor, glypican-3 targeting
      treatments, and anti-CTLA4 treatment. Although some of these novel approaches may
      provide benefit as single agents, there is a clear opportunity in hepatocellular
      carcinoma to evaluate these in combination with the standard modalities to more
      effectively harness the immune response.

PMID- 24030703
TI  - Combined immunostimulatory monoclonal antibodies extend survival in an aggressive
      transgenic hepatocellular carcinoma mouse model.
AB  - PURPOSE: Immunostimulatory monoclonal antibodies (ISmAb) that unleash antitumor
      immune responses are showing efficacy in cancer clinical trials. Anti-B7-H1 (PD
      L1) monoclonal antibodies (mAb) block a critical inhibitory pathway in T cells,
      whereas anti-CD137 and OX40 mAbs provide T-cell costimulation. A combination of
      these ISmAbs (anti-CD137 + anti-OX40 + anti-B7-H1) was tested using a transgenic
      mouse model of multifocal and rapidly progressing hepatocellular carcinoma, in
      which c-myc drives transformation and cytosolic ovalbumin (OVA) is expressed in
      tumor cells as a model antigen. EXPERIMENTAL DESIGN: Flow-cytometry and
      immunohistochemistry were used to quantify tumor-infiltrating lymphocytes (TIL)
      elicited by treatment and assess their activation status and cytolytic potential.
      Tolerance induction and its prevention/reversal by treatment with the combination
      of ISmAbs were revealed by in vivo killing assays. RESULTS: The triple
      combination of ISmAbs extended survival of mice bearing hepatocellular carcinomas
      in a CD8-dependent fashion and synergized with adoptive T-cell therapy using
      activated OVA-specific TCR-transgenic OT-1 and OT-2 lymphocytes. Mice undergoing
      therapy showed clear increases in tumor infiltration by activated and blastic
      CD8(+) and CD4(+) T lymphocytes containing perforin/granzyme B and expressing the
      ISmAb-targeted receptors on their surface. The triple combination of ISmAbs did
      not result in enhanced OVA-specific cytotoxic T lymphocyte (CTL) activity but
      other antigens expressed by cell lines derived from such hepatocellular
      carcinomas were recognized by endogenous TILs. Adoptively transferred OVA
      specific OT-1 lymphocytes into tumor-bearing mice were rendered tolerant, unless
      given the triple mAb therapy. CONCLUSION: Extension of survival and dense T-cell
      infiltrates emphasize the translational potential of combinational immunotherapy
      strategies for hepatocellular carcinoma. Clin Cancer Res; 19(22); 6151-62.
      (c)2013 AACR.

PMID- 24030704
TI  - Tumor stromal architecture can define the intrinsic tumor response to VEGF
      targeted therapy.
AB  - PURPOSE: The aim of the study was to investigate the vascular and stromal
      architecture of preclinical tumor models and patient tumor specimens from
      malignancies with known clinical outcomes to VEGFi treatment, to gain insight
      into potential determinants of intrinsic sensitivity and resistance. EXPERIMENTAL
      DESIGN: The tumor stroma architecture of preclinical and clinical tumor samples
      were analyzed by staining for CD31 and alpha-smooth muscle actin (alpha-SMA).
      Tumor models representative of each phenotype were then tested for sensitivity to
      the VEGFR2-blocking antibody DC101. RESULTS: Human tumor types with high response
      rates to VEGF inhibitors (e.g., renal cell carcinoma) have vessels distributed
      amongst the tumor cells (a "tumor vessel" phenotype, TV). In contrast, those
      malignancies where single-agent responses are lower, such as non-small cell lung
      cancer (NSCLC), display a complex morphology involving the encapsulation of tumor
      cells within stroma that also supports the majority of vessels (a "stromal
      vessel" phenotype). Only 1 of 31 tumor xenograft models displayed the stromal
      vessel phenotype. Tumor vessel models were sensitive to VEGFR2-blocking antibody
      DC101, whereas the stromal vessel models were exclusively refractory. The tumor
      vessel phenotype was also associated with a better Response Evaluation Criteria
      in Solid Tumors (RECIST) response to bevacizumab + chemotherapy in metastatic
      colorectal cancer (CRC). CONCLUSION: The tumor stromal architecture can
      differentiate between human tumor types that respond to a VEGF signaling
      inhibitor as single-agent therapy. In addition to reconciling the clinical
      experience with these agents versus their broad activity in preclinical models,
      these findings may help to select solid tumor types with intrinsic sensitivity to
      a VEGFi or other vascular-directed therapies.

PMID- 24030705
TI  - Oral bisphosphonates and the risk of colorectal cancer: a meta-analysis.
AB  - AIM: : To conduct a meta-analysis on the relationship between the usage of
      bisphosphonates and the risk of colorectal cancer. METHODS: We searched PUBMED
      and EMBASE for studies assessing colorectal cancer incidence or prevalence in
      bisphosphonate users versus nonusers that were published before August 2012. We
      used the STATA software to calculate the pooled odds ratios (OR) and 95%
      confidence interval (CI) for the risk of colorectal cancer associated with
      exposure to bisphosphonates using a random-effects model. RESULTS: Eight studies
      met our inclusion criteria, which comprised 5 cohort studies and 3 case-control
      studies, with a total of 22,291 colorectal cancer cases. The usage of
      bisphosphonates was associated with a statistically significant decrease in
      colorectal cancer risk, with a pooled OR of 0.89 (95% CI, 0.80-0.99). A
      statistically significant decrease in the risk of colorectal cancer was observed
      in the long-term exposure groups (pooled OR, 0.73; 95% CI, 0.57-0.93).
      CONCLUSIONS: These results indicate that the decrease in risk of colorectal
      cancer may be associated with the usage of bisphosphonates. More studies are
      needed to confirm the relationship.

PMID- 24030706
TI  - Patient perspectives of dabigatran: analysis of online discussion forums.
AB  - BACKGROUND: In 2010 the US FDA approved dabigatran, the first new anticoagulant
      for stroke prevention in non-valvular atrial fibrillation (AF) since 1954. To
      date there is little data that reflects the experiences and perceptions of real
      world patients with dabigatran. The abundance of Internet-based discussion forums
      and support groups related to AF or anticoagulation may provide a low-cost
      resource for assessing patient experiences. OBJECTIVE: The aim of this study was
      to determine patient experiences and perceptions regarding dabigatran through
      qualitative thematic content analysis of comments posted on publicly accessible
      virtual discussion forums and Internet support groups. MEASUREMENTS: Comments
      posted between January 2011 and September 2012 were downloaded from websites
      focusing on support of patients with AF or on anticoagulation therapy. Comments
      were analyzed for thematic content. RESULTS: Five broad thematic categories
      emerged from the posted comments: general concerns about safety and efficacy,
      questions about indications and contraindications, questions about proper use and
      storage, questions about diet and drug restrictions, and experiences with
      perceived side effects. Our data revealed that a primary concern for patients
      taking dabigatran is the lack of antidote to reverse the effects of dabigatran if
      bleeding occurs. Several questions pertaining to the use of dabigatran with other
      medications or medical conditions were noted, and multiple patients expressed
      confusion about instructions for using dabigatran before and after medical
      procedures. An unexpected finding included several criticisms of the medication
      packaging, which many patients found inconvenient or difficult to open. Finally,
      several perceived side effects were noted, including some not reported in
      clinical trials. CONCLUSIONS: Online communities may provide information about
      topics that are a concern to patients and that may not be discernible in clinical
      trials, such as medication side effects, proper use, and safety. Our data also
      highlighted potential topics that may not be a priority to researchers but are
      nevertheless important to patients (e.g. medication convenience or packaging).
      Despite the growing use of online health-related communities, very little
      research makes use of this low-cost resource for identifying patient interests
      regarding therapeutic treatments to guide patient-oriented research.

PMID- 24030707
TI  - Red cell-derived microparticles (RMP) as haemostatic agent.
AB  - Among circulating cell-derived microparticles, those derived from red cells (RMP)
      have been least well investigated. To exploit potential haemostatic benefit of
      RMP, we developed a method of producing them in quantity, and here report on
      their haemostatic properties. High-pressure extrusion of washed RBC was employed
      to generate RMP. RMP were identified and enumerated by flow cytometry. Their size
      distribution was assessed by Doppler electrophoretic light scattering analysis
      (DELSA). Interaction with platelets was studied by platelet aggregometry, and
      shear-dependent adhesion by Diamed IMPACT-R. Thrombin generation and tissue
      factor (TF) expression was also measured. The effect of RMP on blood samples of
      patients with bleeding disorders was investigated ex vivo by thromboelastography
      (TEG). Haemostatic efficacy in vivo was assessed by measuring reduction of blood
      loss and bleeding time in rats and rabbits. RMP have mean diameter of 0.45 um and
      50% of them exhibit annexin V binding, a proxy for procoagulant phospholipids
      (PL). No TF could be detected by flow cytometry. At saturating concentrations of
      MPs, RMP generated thrombin robustly but after longer delay compared to PMP and
      EMP. RMP enhanced platelet adhesion and aggregation induced by low-dose ADP or
      AA. In TEG study, RMP corrected or improved haemostatic defects in blood of
      patients with platelet and coagulation disorders. RMP reduced bleeding time and
      blood loss in thrombocytopenic rabbits (busulfan-treated) and in Plavix-treated
      rats. In conclusion, RMP has broad haemostatic activity, enhancing both primary
      (platelet) and secondary (coagulation) haemostasis, suggesting potential use as
      haemostatic agent for treatment of bleeding. 

PMID- 24030708
TI  - Caesarean section versus vaginal delivery for preterm birth in singletons.
AB  - BACKGROUND: Planned caesarean delivery for women thought be in preterm labour may
      be protective for baby, but could also be quite traumatic for both mother and
      baby. The optimal mode of delivery of preterm babies for both cephalic and breech
      presentation remains, therefore, controversial. OBJECTIVES: To assess the effects
      of a policy of planned immediate caesarean delivery versus planned vaginal birth
      for women in preterm labour. SEARCH METHODS: We searched the Cochrane Pregnancy
      and Childbirth Group's Trials Register (5 August 2013). SELECTION CRITERIA:
      Randomised trials comparing a policy of planned immediate caesarean delivery
      versus planned vaginal delivery for preterm birth. DATA COLLECTION AND ANALYSIS:
      Two review authors independently assessed trials for inclusion. Two review
      authors independently extracted data and assessed risk of bias. Data were checked
      for accuracy. MAIN RESULTS: We included six studies (involving 122 women) but
      only four studies (involving only 116 women) contributed data to the analyses.
      INFANT: There were very little data of relevance to the three main (primary)
      outcomes considered in this review: There was no significant difference between
      planned immediate caesarean section and planned vaginal delivery with respect to
      birth injury to infant (risk ratio (RR) 0.56, 95%, confidence interval (CI) 0.05
      to 5.62; one trial, 38 women) or birth asphyxia (RR 1.63, 95% CI 0.84 to 3.14;
      one trial, 12 women). The only cases of birth trauma were a laceration of the
      buttock in a baby who was delivered by caesarean section and mild bruising in
      another allocated to the group delivered vaginally.The difference between the two
      groups with regard to perinatal deaths was not significant (0.29, 95% CI 0.07 to
      1.14; three trials, 89 women) and there were no data specifically relating to
      neonatal admission to special care and/or intensive care unit.There was also no
      difference between the caesarean or vaginal delivery groups in terms of markers
      of possible birth asphyxia (RR 1.63, 95% CI 0.84 to 3.14; one trial, 12 women) or
      Apgar score less than seven at five minutes (RR 0.83, 95% CI 0.43 to 1.60; four
      trials, 115 women) and no difference in attempts at breastfeeding (RR 1.40, 95%
      0.11 to 17.45; one trial, 12 women). There was also no difference in neonatal
      fitting/seizures (RR 0.22, 95% CI 0.01 to 4.32; three trials, 77 women), hypoxic
      ischaemic encephalopathy (RR 4.00, 95% CI 0.20 to 82.01;one trial, 12 women) or
      respiratory distress syndrome (RR 0.55, 95% CI 0.27 to 1.10; three trials, 103
      women). There were no data reported in the trials specifically relating to
      meconium aspiration. There was also no significant difference between the two
      groups for abnormal follow-up in childhood (RR 0.65, 95% CI 0.19 to 2.22; one
      trial, 38 women) or delivery less than seven days after entry (RR 0.95, 95% CI
      0.73 to 1.24; two trials, 51 women). MOTHER: There were no data reported on
      maternal admissions to intensive care. However, there were seven cases of major
      maternal postpartum complications in the group allocated to planned immediate
      caesarean section and none in the group randomised to vaginal delivery (RR 7.21,
      95% CI 1.37 to 38.08; four trials, 116 women).There were no data reported in the
      trials specifically relating to maternal satisfaction (postnatal). There was no
      significant difference between the two groups with regard to postpartum
      haemorrhage. A number of non-prespecified secondary outcomes were also considered
      in the analyses. There was a significant advantage for women in the vaginal
      delivery group with respect to maternal puerperal pyrexia (RR 2.98, 95% CI 1.18
      to 7.53; three trials, 89 women) and other maternal infection (RR 2.63, 95% CI
      1.02 to 6.78; three trials, 103 women), but no significant differences in wound
      infection (RR 1.16, 95% CI 0.18 to 7.70; three trials, 103 women), maternal stay
      more than 10 days (RR 1.27, 95% CI 0.35 to 4.65; three trials, 78 women) or the
      need for blood transfusion (results not estimable). AUTHORS' CONCLUSIONS: There
      is not enough evidence to evaluate the use of a policy of planned immediate
      caesarean delivery for preterm babies. Further studies are needed in this area,
      but recruitment is proving difficult.

PMID- 24030709
TI  - Boronic acid functionalized graphene quantum dots as a fluorescent probe for
      selective and sensitive glucose determination in microdialysate.
AB  - 3-Aminobenzeneboronic acid functionalized graphene quantum dots (APBA-GQDs) were
      synthesized and used as a selective and sensitive sensing system for glucose.
      Combined with microdialysis, glucose was monitored successfully in vivo in the
      striatum of rat. 

PMID- 24030710
TI  - In vitro optimization of 2'-OMe-4'-thioribonucleoside-modified anti-microRNA
      oligonucleotides and its targeting delivery to mouse liver using a liposomal
      nanoparticle.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post
      transcriptionally. Previous studies, which characterized miRNA function, revealed
      their involvement in fundamental biological processes. Importantly, miRNA
      expression is deregulated in many human diseases. Specific inhibition of miRNAs
      using chemically modified anti-miRNA oligonucleotides (AMOs) can be a potential
      therapeutic strategy for diseases in which a specific miRNA is overexpressed. 2'
      O-Methyl (2'-OMe)-4'-thioRNA is a hybrid type of chemically modified
      oligonucleotide, exhibiting high binding affinity to complementary RNAs and high
      resistance to nuclease degradation. Here, we evaluate 2'-OMe-4'
      thioribonucleosides for chemical modification on AMOs. Optimization of the
      modification pattern using a variety of chemically modified AMOs that are
      perfectly complementary to mature miR-21 revealed that the uniformly 2'-OMe-4'
      thioribonucleoside-modified AMO was most potent. Further investigation showed
      that phosphorothioate modification contributed to long-term miR-122 inhibition by
      the 2'-OMe-4'-thioribonucleoside-modified AMO. Moreover, systemically
      administrated AMOs to mouse using a liposomal delivery system, YSK05-MEND, showed
      delivery to the liver and efficient inhibition of miR-122 activity at a low dose
      in vivo. 

PMID- 24030711
TI  - Purification of a specific native genomic locus for proteomic analysis.
AB  - Here, we describe an approach to isolate native chromatin sections without
      genomic engineering for label-free proteomic identification of associated
      proteins and histone post-translational modifications. A transcription activator
      like (TAL) protein A fusion protein was designed to recognize a unique site in
      the yeast GAL1 promoter. The TAL-PrA fusion enabled chromatin affinity
      purification (ChAP) of a small section of native chromatin upstream from the GAL1
      locus, permitting mass spectrometric (MS) identification of proteins and histone
      post-translational modifications regulating galactose-induced transcription. This
      TAL-ChAP-MS approach allows the biochemical isolation of a specific native
      genomic locus for proteomic studies and will provide for unprecedented objective
      insight into protein and epigenetic mechanisms regulating site-specific
      chromosome metabolism. 

PMID- 24030712
TI  - In-cell optical imaging of exogenous G-quadruplex DNA by fluorogenic ligands.
AB  - Guanine-rich oligonucleotides (GROs) are promising therapeutic candidate for
      cancer treatment and other biomedical application. We have introduced a G
      quadruplex (G4) ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide,
      to monitor the cellular uptake of naked GROs and map their intracellular
      localizations in living cells by using confocal microscopy. The GROs that form
      parallel G4 structures, such as PU22, T40214 and AS1411, are detected mainly in
      the lysosome of CL1-0 lung cancer cells after incubation for 2 h. On the
      contrary, the GROs that form non-parallel G4 structures, such as human telomeres
      (HT23) and thrombin binding aptamer (TBA), are rarely detected in the lysosome,
      but found mainly in the mitochondria. Moreover, the fluorescence resonant energy
      transfer studies of fluorophore-labeled GROs show that the parallel G4 structures
      can be retained in CL1-0 cells, whereas the non-parallel G4 structures are likely
      distorted in CL1-0 cells after cellular uptake. Of interest is that the distorted
      G4 structure of HT23 from the non-parallel G4 structure can reform to a probable
      parallel G4 structure induced by a G4 ligand in CL1-0 living cells. These
      findings are valuable to the design and rationale behind the possible targeted
      drug delivery to specific cellular organelles using GROs. 

PMID- 24030714
TI  - Neonatal hemochromatosis: management, outcome, and prevention.
AB  - Neonatal hemochromatosis (NH) is a rare disorder but the most common cause of
      acute liver failure in neonates. NH is characterized by severe hepatic injury and
      iron overload and is associated with high perinatal mortality and morbidity
      rates. NH is often preceded by oligohydramnios and intrauterine growth
      restriction, suggesting an important impact of NH during fetal life. Stillbirth
      and prematurity are not uncommon. During the last decade, major discoveries on
      the etiology of NH have radically changed the management and outcome of this
      disease. NH is now regarded as an alloimmune disease and is, as such, often
      referred to as gestational alloimmune liver disease. Antenatal treatment with
      intravenous immunoglobulins starting at 14 weeks' gestation has been shown to
      prevent the development of NH in subsequent pregnancies. Postnatal treatment,
      previously based on the use of anti-oxidants and chelation therapy, has now
      successfully been replaced by exchange transfusions and intravenous
      immunoglobulins substitution. This review summarizes the latest discoveries on
      the etiology of NH and the new recommendations concerning its management and
      prevention.

PMID- 24030713
TI  - Dissecting the oligonucleotide binding properties of a disordered chaperone
      protein using surface plasmon resonance.
AB  - We have used surface plasmon resonance to investigate the nucleic acid binding
      properties of the core protein of hepatitis C virus, a disordered protein
      believed to chaperone the genomic RNA. It was previously shown that a peptide
      (peptide E) corresponding to the association of two basic clusters of core
      enhances the annealing and the dimerization of nucleic acid fragments derived
      from a stem loop (SL2) in the 3' untranslated region of the hepatitis C virus
      genome. However, strong aggregation of nucleic acids by core or peptide E in the
      excess of the latter precluded the characterization of their binding parameters
      up to now. By careful design of surface plasmon resonance experiments, we
      obtained accurate binding parameters for the interaction of peptide E with SL2
      derived oligonucleotides of different lengths and sequences, in form of stem
      loop, duplex or strand. Peptide E was found to bind in a salt dependent manner to
      all oligonucleotides assayed. Affinity data identify at least two binding modes,
      of which one is independent of sequence/structure, and the other is specific to
      the SL2 stem-loop fold. Stoichiometry data support a multi-motif binding model
      allowing formation of higher-order complexes. We propose that the modular binding
      mode demonstrated for structured RNA-binding proteins also applies to this
      disordered chaperone and is relevant to its activity. 

PMID- 24030715
TI  - A new receptor with a FRET based fluorescence response for selective recognition
      of fumaric and maleic acids in aqueous medium.
AB  - Preferential binding of a new reagent to fumaric acid could be utilized for its
      estimation in aqueous medium and in commercial fruit juice. 

PMID- 24030716
TI  - Suprafascial pre-expansion of perforator flaps and the effect of pre-expansion on
      perforator artery diameter.
AB  - BACKGROUND: This study addresses the "pre-expanded perforator flap concept" by
      demonstrating a case series of relevant reconstructive procedures and evaluate
      the perforator vessel diameter changes that happen during the pre-expansion
      procedure. METHODS: Fourteen patients were treated with 15 flaps. One patient was
      treated with two pre-expanded internal mammary artery perforator flaps. In other
      cases, thoracodorsal, circumflex scapular, lumbar, intercostal, lateral
      circumflex femoral, and deep inferior epigastric artery perforator flaps were
      used. Technical details and rate of complications were noted. Evaluations of the
      flap pedicles were done both by hand held Doppler and by color Doppler ultrasound
      (CDU). RESULTS: Flaps successfully served to resurface and release thick and
      rigid broad scar tissues and contractures in 11 of relevant 12 patients (in one
      patient with 50% flap loss, adequate contracture release could only be obtained
      with addition of a secondary split thickness skin graft to the residual flap) and
      provided a good source of tissue for anterior neck reconstruction of one patient
      and penis reconstruction of another patient. In six patients, perforator artery
      diameters were measured by CDU both before and after the expansion process and a
      significant increase secondary to the pre-expansion procedure was detected (Pre
      expansion mean: 0.48 +/- 0.08 mm; post-expansion mean: 0.65 +/- 0.10 mm; P <
      0.05). Flaps as large as 30 * 20 cm were harvested. Totally three partial flap
      necroses were experienced in 15 flap procedures. CONCLUSIONS: Suprafascial pre
      expansion of the perforator flaps seems to provide a solution to achieve broader
      and thinner perforator flaps with larger perforator arteries.

PMID- 24030717
TI  - Discrimination of Aspergillus lentulus from Aspergillus fumigatus by Raman
      spectroscopy and MALDI-TOF MS.
AB  - In 2005, a new sibling species of Aspergillus fumigatus was discovered:
      Aspergillus lentulus. Both species can cause invasive fungal disease in immune
      compromised patients. The species are morphologically very similar. Current
      techniques for identification are PCR-based or morphology-based. These techniques
      are labour-intense and not sufficiently discriminatory. Since A. lentulus is less
      susceptible to several antifungal agents, it is important to correctly identify
      the causative infectious agent in order to optimize antifungal therapy. In this
      study we determined whether Raman spectroscopy and/or MALDI-TOF MS were able to
      differentiate between A. lentulus and A. fumigatus. For 16 isolates of A.
      lentulus and 16 isolates of A. fumigatus, Raman spectra and peptide profiles were
      obtained using the Spectracell and MALDI-TOF MS (VITEK MS RUO, bioMerieux)
      respectively. In order to obtain reliable Raman spectra for A. fumigatus and A.
      lentulus, the culture medium needed to be adjusted to obtain colourless conidia.
      Only Raman spectra obtained from colourless conidia were reproducible and
      correctly identified 25 out of 32 (78 %) of the Aspergillus strains. For VITEK MS
      RUO, no medium adjustments were necessary. Pigmented conidia resulted in
      reproducible peptide profiles as well in this case. VITEK MS RUO correctly
      identified 100 % of the Aspergillus isolates, within a timeframe of approximately
      54 h including culture. Of the two techniques studied here, VITEK MS RUO was
      superior to Raman spectroscopy in the discrimination of A. lentulus from A.
      fumigatus. VITEK MS RUO seems to be a successful technique in the daily
      identification of Aspergillus spp. within a limited timeframe.

PMID- 24030718
TI  - Ceftobiprole medocaril is an effective treatment against methicillin-resistant
      Staphylococcus aureus (MRSA) mediastinitis in a rat model.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis after median
      sternotomy is a major complication of cardiac surgery with significant morbidity
      and mortality rates. We evaluated the efficacy of ceftobiprole medocaril in a new
      rat model of mediastinitis and compared it to vancomycin. The model was induced
      in 92 rats. Infection was induced immediately after median sternotomy by the
      injection of MRSA (strain 3020, 1 * 10(7) cfu/rat) into the sternal bone. After
      24 h, rats (groups of 6-8) were treated intraperitoneally for 5 days or 14 days
      by either: (i) saline (control, q8h), (ii) ceftobiprole medocaril (70 or 100
      mg/kg, q8h), or (iii) vancomycin (50 mg/kg, q12h). Efficacy was determined by a
      reduction in bacterial cfu in the sternum and spleen tissues. Comparisons were
      performed using the Mann-Whitney test. A 5-day treatment course of ceftobiprole
      at both doses tested lead to a significant reduction in MRSA load in the sternum
      (p < 0.01) as compared to the control group and compared to 5-day vancomycin
      treatment, which lead to a non-significant reduction (p = 0.07). Longer treatment
      (14 days) with ceftobiprole lead to a complete clearance of MRSA from the
      sternum, similarly to vancomycin. Ceftobiprole also showed a significant effect
      on eliminating MRSA dissemination to the spleen compared to saline-treated rats.
      Ceftobiprole was effective in treating MRSA mediastinitis in the rat model. In
      the 5-day course, ceftobiprole showed a significant reduction in sternal MRSA
      counts and was superior to vancomycin. After 14 days, both ceftobiprole and
      vancomycin showed clearance of MRSA from the sternum in more than 50 % of rats
      and almost complete clearance in the remainder.

PMID- 24030719
TI  - Design of superparamagnetic nanoparticles for magnetic particle imaging (MPI).
AB  - Magnetic particle imaging (MPI) is a promising medical imaging technique
      producing quantitative images of the distribution of tracer materials
      (superparamagnetic nanoparticles) without interference from the anatomical
      background of the imaging objects (either phantoms or lab animals).
      Theoretically, the MPI platform can image with relatively high temporal and
      spatial resolution and sensitivity. In practice, the quality of the MPI images
      hinges on both the applied magnetic field and the properties of the tracer
      nanoparticles. Langevin theory can model the performance of superparamagnetic
      nanoparticles and predict the crucial influence of nanoparticle core size on the
      MPI signal. In addition, the core size distribution, anisotropy of the magnetic
      core and surface modification of the superparamagnetic nanoparticles also
      determine the spatial resolution and sensitivity of the MPI images. As a result,
      through rational design of superparamagnetic nanoparticles, the performance of
      MPI could be effectively optimized. In this review, the performance of
      superparamagnetic nanoparticles in MPI is investigated. Rational synthesis and
      modification of superparamagnetic nanoparticles are discussed and summarized. The
      potential medical application areas for MPI, including cardiovascular system,
      oncology, stem cell tracking and immune related imaging are also analyzed and
      forecasted.

PMID- 24030720
TI  - Berry phenolics of grapevine under challenging environments.
AB  - Plant phenolics have been for many years a theme of major scientific and applied
      interest. Grape berry phenolics contribute to organoleptic properties, color and
      protection against environmental challenges. Climate change has already caused
      significant warming in most grape-growing areas of the world, and the climatic
      conditions determine, to a large degree, the grape varieties that can be
      cultivated as well as wine quality. In particular, heat, drought and light/UV
      intensity severely affect phenolic metabolism and, thus, grape composition and
      development. In the variety Chardonnay, water stress increases the content of
      flavonols and decreases the expression of genes involved in biosynthesis of
      stilbene precursors. Also, polyphenolic profile is greatly dependent on genotype
      and environmental interactions. This review deals with the diversity and
      biosynthesis of phenolic compounds in the grape berry, from a general overview to
      a more detailed level, where the influence of environmental challenges on key
      phenolic metabolism pathways is approached. The full understanding of how and
      when specific phenolic compounds accumulate in the berry, and how the varietal
      grape berry metabolism responds to the environment is of utmost importance to
      adjust agricultural practices and thus, modify wine profile.

PMID- 24030721
TI  - The MAPKKK gene family in Gossypium raimondii: genome-wide identification,
      classification and expression analysis.
AB  - Mitogen-activated protein kinase (MAPK) cascades are conserved signal
      transduction pathways in all eukaryotic organisms. MAPKKKs (MAPK kinase kinases)
      operate at the top levels of these cascades. Recently, this family of genes has
      been systematically investigated in Arabidopsis, rice and maize, but has not yet
      been characterized in cotton. In this study, we identified 78 putative MAPKKK
      genes in the genome of the diploid cotton, Gossypium raimondii. They were
      classified into three subfamilies, of which 12 were ZIK, 22 were MEKK and 44 were
      Raf. The ZIK and MEKK genes displayed a scattered genomic distribution across 11
      of the 13 chromosomes, whereas Raf genes were distributed across the entire
      genome. Their conserved patterns observed for introns and additional domains were
      consistent with the evolutionary relationships inferred from the phylogenetic
      analysis within subfamily. Transcriptome sequencing data were used to investigate
      their transcript profiles in mature leaves, 0 day and 3 days post-anthesis (DPA)
      ovules. Sixty MAPKKK genes were expressed, of which 41 were strongly expressed in
      mature leaves. Twelve MAPKKK genes were more highly expressed in 3-DPA ovules
      than in 0-DPA ovules. Our results provide a foundation for future evolutionary
      and functional characterizations of MAPKKK genes in cotton and probably other
      Gossypium plants.

PMID- 24030724
TI  - Water reduction with visible light: synergy between optical transitions and
      electron transfer in Au-TiO(2) catalysts visualized by in situ EPR spectroscopy.
AB  - Golden electrons: Visible light excites conduction electron transfer from gold
      particles to support vacancies where they are taken up by protons to produce
      hydrogen. This transfer process was visualized by in situ EPR spectroscopy. 

PMID- 24030723
TI  - Case-crossover study design in pharmacoepidemiology: systematic review and
      recommendations.
AB  - PURPOSE: The purpose of this study is to systematically identify and review
      articles that use the case-crossover study design in the area of
      pharmacoepidemiology. METHODS: A systematic search of MEDLINE(r) (Ovid
      Technologies, New York City, NY, USA), EMBASE(r) (Elsevier Inc., Philadelphia,
      PA, USA), and Web of Science(r) (Thomson Reuters, New York City, NY, USA) was
      completed to identify all English language articles that applied the case
      crossover study design in the area of pharmacoepidemiology. The number of
      reviews, methodological contributions, and empirical pharmacoepidemiologic
      applications were summarized by publication year. Empirical applications were
      retrieved, and methodological details (outcome, exposure, exposure windows,
      sensitivity analysis, statistical reporting) were tabulated and compared to
      methodological recommendations based on exposure characteristics, exposure
      windows, and discordant pairs data display. RESULTS: Of 836 unique articles
      identified, 99 pharmacoepidemiologic studies were eligible: 20 methodological
      contributions, 9 review papers, and 70 empirical applications. Only three
      empirical applications in the area of pharmacoepidemiology were published before
      2000. Since 2000, the number of empirical pharmacoepidemiologic applications
      published annually has generally increased over time, to before a high of 15
      published in 2011. The design was mainly applied to examine drug safety (96%),
      and most applications investigated: psychotropic (24%) and analgesic (17%)
      exposure drug classes; and considered hospitalization (23%) and
      cardiovascular/cerebrovascular (21%) events. Only 31% of applications displayed
      sufficient data to enable readers to confirm odds ratios presented. CONCLUSIONS:
      Use of the case-crossover design in pharmacoepidemiology has increased rapidly in
      the last decade. As the application of the case-crossover design continues to
      increase, it is important to develop standards of practice, especially for
      display of data.

PMID- 24030722
TI  - Feasibility and effectiveness of a low cost campaign on antibiotic prescribing in
      Italy: community level, controlled, non-randomised trial.
AB  - OBJECTIVES: To test the hypothesis that a multifaceted, local public campaign
      could be feasible and influence antibiotic prescribing for outpatients. DESIGN:
      Community level, controlled, non-randomised trial. SETTING: Provinces of Modena
      and Parma in Emilia-Romagna, northern Italy, November 2011 to February 2012.
      POPULATION: 1,150,000 residents of Modena and Parma (intervention group) and
      3,250,000 residents in provinces in the same region but where no campaign had
      been implemented (control group). INTERVENTIONS: Campaign materials (mainly
      posters, brochures, and advertisements on local media, plus a newsletter on local
      antibiotic resistance targeted at doctors and pharmacists). General practitioners
      and paediatricians in the intervention area participated in designing the
      campaign messages. MAIN OUTCOMES MEASURES: Primary outcome was the average change
      in prescribing rates of antibiotics for outpatient in five months, measured as
      defined daily doses per 1000 inhabitants/day, using health districts as the unit
      of analysis. RESULTS: Antibiotic prescribing was reduced in the intervention area
      compared with control area (-4.3%, 95% confidence interval -7.1% to -1.5%). This
      result was robust to "sensitivity analysis" modifying the baseline period from
      two months (main analysis) to one month. A higher decrease was observed for
      penicillins resistant to beta lactamase and a lower decrease for penicillins
      susceptible to beta lactamase, consistent with the content of the newsletter on
      antibiotic resistance directed at health professionals. The decrease in
      expenditure on antibiotics was not statistically significant in a district level
      analysis with a two month baseline period (main analysis), but was statistically
      significant in sensitivity analyses using either a one month baseline period or a
      more powered doctor level analysis. Knowledge and attitudes of the target
      population about the correct use of antibiotics did not differ between the
      intervention and control areas. CONCLUSIONS: A local low cost information
      campaign targeted at citizens, combined with a newsletter on local antibiotic
      resistance targeted at doctors and pharmacists, was associated with significantly
      decreased total rates of antibiotic prescribing but did not affect the
      population's knowledge and attitudes about antibiotic resistance. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01604096.

PMID- 24030725
TI  - Can legislation aimed at preventing sports-related concussions in youth succeed?

PMID- 24030727
TI  - Polymers for electronics and spintronics.
AB  - This critical review is devoted to semiconducting and high spin polymers which
      are of great scientific interest in view of further development of the organic
      electronics and the emerging organic spintronic fields. Diversified synthetic
      strategies are discussed in detail leading to high molecular mass compounds
      showing appropriate redox (ionization potential (IP), electron affinity (EA)),
      electronic (charge carrier mobility, conductivity), optoelectronic
      (electroluminescence, photoconductivity) and magnetic (magnetization,
      ferromagnetic spin interactions) properties and used as active components of
      devices such as n- and p-channel field effect transistors, ambipolar light
      emitting transistors, light emitting diodes, photovoltaic cells, photodiodes,
      magnetic photoswitches, etc. Solution processing procedures developed with the
      goal of depositing highly ordered and oriented films of these polymers are also
      described. This is completed by the description of principal methods that are
      used for characterizing these macromolecular compounds both in solution and in
      the solid state. These involve various spectroscopic methods (UV-vis-NIR, UPS,
      pulse EPR), electrochemistry and spectroelectrochemistry, magnetic measurements
      (SQUID), and structural and morphological investigations (X-ray diffraction, STM,
      AFM). Finally, four classes of polymers are discussed in detail with special
      emphasis on the results obtained in the past three years: (i) high IP, (ii) high
      |EA|, (iii) low band gap and (iv) high spin ones. 

PMID- 24030728
TI  - Dental caries and head and neck cancers.
AB  - IMPORTANCE: Dental caries is the demineralization of tooth structures by lactic
      acid from fermentation of carbohydrates by commensal gram-positive bacteria.
      Cariogenic bacteria have been shown to elicit a potent Th1 cytokine polarization
      and a cell-mediated immune response. OBJECTIVE: To test the association between
      dental caries and head and neck squamous cell carcinoma (HNSCC). DESIGN, SETTING,
      AND PARTICIPANTS: Case-control study in a comprehensive cancer center including
      all patients with newly diagnosed primary HNSCC between 1999 and 2007 as cases
      and all patients without a cancer diagnosis as controls. Those with a history of
      cancer, dysplasia, or immunodeficiency or who were younger than 21 years were
      excluded. EXPOSURES: Dental caries, fillings, crowns, and endodontic treatments,
      measured by the number of affected teeth; missing teeth. We also computed an
      index variable: decayed, missing, and filled teeth (DMFT). MAIN OUTCOMES AND
      MEASURES: Incident HNSCC. RESULTS: We included 620 participants (399 cases and
      221 controls). Cases had a significantly lower mean (SD) number of teeth with
      caries (1.58 [2.52] vs 2.04 [2.15]; P = .03), crowns (1.27 [2.65] vs 2.10 [3.57];
      P = .01), endodontic treatments (0.56 [1.24] vs 1.01 [2.04]; P = .01), and
      fillings (5.39 [4.31] vs 6.17 [4.51]; P = .04) but more missing teeth (13.71
      [10.27] vs 8.50 [8.32]; P < .001) than controls. There was no significant
      difference in mean DMFT. After adjustment for age at diagnosis, sex, marital
      status, smoking status, and alcohol use, those in the upper tertiles of caries
      (odds ratio [OR], 0.32 [95% CI, 0.19-0.55]; P for trend = .001), crowns (OR, 0.46
      [95% CI, 0.26-0.84]; P for trend = .03), and endodontic treatments (OR, 0.55 [95%
      CI, 0.30-1.01]; P for trend = .15) were less likely to have HNSCC than those in
      the lower tertiles. Missing teeth was no longer associated with HNSCC after
      adjustment for confounding. CONCLUSIONS AND RELEVANCE: There is an inverse
      association between HNSCC and dental caries. This study provides insights for
      future studies to assess potential beneficial effects of lactic acid bacteria and
      the associated immune response on HNSCC.

PMID- 24030726
TI  - Pax6-dependent cortical glutamatergic neuronal differentiation regulates autism
      like behavior in prenatally valproic acid-exposed rat offspring.
AB  - Imbalance in excitatory/inhibitory signal in the brain has been proposed as one
      of the main pathological features in autism spectrum disorders, although the
      underlying cellular and molecular mechanism is unclear yet. Because
      excitatory/inhibitory imbalance can be induced by aberration in
      glutamatergic/GABAergic neuronal differentiation, we investigated the mechanism
      of dysregulated neuronal differentiation between excitatory and inhibitory
      neurons in the embryonic and postnatal brain of prenatally valproic acid-exposed
      rat offspring, which is often used as an animal model of autism spectrum
      disorders. Transcription factor Pax6, implicated in glutamatergic neuronal
      differentiation, was transiently increased in embryonic cortex by valproate
      exposure, which resulted in the increased expression of glutamatergic proteins in
      postnatal brain of offspring. Chromatin immunoprecipitation showed increased
      acetylated histone binding on Pax6 promoter region, which may underlie the
      transcriptional up-regulation of Pax6. Other histone deacetylase (HDAC)
      inhibitors including TSA and SB but not valpromide, which is devoid of HDAC
      inhibitor activity, induced Pax6 up-regulation. Silencing Pax6 expression in
      cultured rat primary neural progenitor cells demonstrated that up-regulation of
      Pax6 plays an essential role in valproate-induced glutamatergic differentiation.
      Blocking glutamatergic transmission with MK-801 or memantine treatment, and to a
      lesser extent with MPEP treatment, reversed the impaired social behaviors and
      seizure susceptibility of prenatally valproate-exposed offspring. Together,
      environmental factors may contribute to the imbalance in excitatory/inhibitory
      neuronal activity in autistic brain by altering expression of transcription
      factors governing glutamatergic/GABAergic differentiation during fetal neural
      development, in conjunction with the genetic preload. 

PMID- 24030730
TI  - A novel reaction of gem-difluorocyclopropyl ketones with nitriles leading to 2
      fluoropyrroles.
AB  - The CF3SO3H-promoted ring opening of gem-difluorocyclopropyl ketones prefers to
      undergo proximal bond cleavage and the subsequent cyclization with nitriles
      occurred smoothly to give 2-fluoropyrroles. 

PMID- 24030729
TI  - FLT3-ITD and MLL-PTD influence the expression of MDR-1, MRP-1, and BCRP mRNA but
      not LRP mRNA assessed with RQ-PCR method in adult acute myeloid leukemia.
AB  - Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) and mixed
      lineage leukemia gene-partial tandem duplication (MLL-PTD) are aberrations
      associated with leukemia which indicate unsatisfactory prognosis. Downstream
      regulatory targets of FLT3-ITD and MLL-PTD are not well defined. We have analyzed
      the expression of MDR-1, multidrug resistant protein-1 (MRP-1), breast cancer
      resistance protein (BCRP), and lung resistance protein (LRP) messenger RNA (mRNA)
      in relation to the mutational status of FLT3-ITD and MLL-PTD in 185 acute myeloid
      leukemia (AML) adult patients. The real-time quantitative polymerase chain
      reaction method was performed to assess the expression of the MDR-1, MRP-1, BCRP,
      and LRP mRNA, and the results were presented as coefficients calculated using an
      intermediate method according to Pfaffl's rule. Significantly higher expressions
      of MDR-1 mRNA were found in patients who did not harbor FLT3-ITD (0.20 vs. 0.05;
      p = 0.0001) and MRP-1 mRNA in patients with this mutation (0.96 vs. 0.70; p =
      0.002) and of BCRP mRNA in patients with MLL-PTD (0.61 vs. 0.38; p = 0.03). In
      univariate analysis, the high expression of MDR-1 mRNA (>=0.1317) negatively
      influenced the outcome of induction therapy (p = 0.05), whereas the high
      expression of BCRP mRNA (>=1.1487) was associated with a high relapse rate (RR)
      (p = 0.013). We found that the high expression of MDR-1 (>=0.1317), MRP-1
      (>=0.8409), and BCRP mRNA (>=1.1487) significantly influenced disease-free
      survival (DFS; p = 0.059, 0.032, and 0.009, respectively) and overall survival
      (0.048, 0.014, and 0.059, respectively). Moreover, a high expression of BCRP mRNA
      (>=1.1487) proved to be an independent prognostic factor for RR (p = 0.01) and
      DFS (p = 0.002) in multivariate analysis. The significant correlation between the
      expression of MDR-1, MRP-1, and BCRP mRNA and FLT3-ITD or MLL-PTD in AML patients
      requires further investigation.

PMID- 24030731
TI  - A redox-responsive cationic supramolecular polymer constructed from small
      molecules as a promising gene vector.
AB  - A novel class of redox-responsive cationic supramolecular polymer with effective
      DNA condensation ability and H2O2-induced DNA release behavior has been
      successfully constructed from small molecules. This supramolecular polymer can be
      used in vitro as a promising nonviral vector for gene therapy. 

PMID- 24030733
TI  - Atomic and electronic structure of an alloyed topological insulator,
      Bi1.5Sb0.5Te1.7Se1.3.
AB  - Bi2-xSbxTe3-ySey has been argued to exhibit both topological surface states and
      insulating bulk states, but has not yet been studied with local probes on the
      atomic scale. Here we report on the atomic and electronic structures of
      Bi1.5Sb0.5Te1.7Se1.3 studied using scanning tunnelling microscopy (STM) and
      spectroscopy (STS). Although there is significant surface disorder due to
      alloying of constituent atoms, cleaved surfaces of the crystals present a well
      ordered hexagonal lattice with 10 A high quintuple layer steps. STS results
      reflect the band structure and indicate that the surface state and Fermi energy
      are both located inside the energy gap. In particular, quasi-particle
      interference patterns from electron scattering demonstrate that the surface
      states possess linear dispersion and chirality from spin texture, thus verifying
      its topological nature. This finding demonstrates that alloying is a promising
      route to achieve full suppression of bulk conduction in topological insulators
      whilst keeping the topological surface state intact. 

PMID- 24030734
TI  - Prophylactic use of transjugular intrahepatic portosystemic shunt aids in the
      treatment of refractory ascites: metaregression and trial sequential meta
      analysis.
AB  - GOALS: The aim of this study was to explore whether prophylactic use of
      transjugular intrahepatic portosystemic shunt (TIPS) could aid in the treatment
      of refractory ascites on the basis of current randomized controlled trials.
      BACKGROUND: TIPS is more effective for refractory ascites versus large-volume
      paracentesis. At present, however, the survival advantage is not clear within
      populations of undifferentiated patients. STUDY: Correlative studies were
      searched through online journal databases, and a manual search was done from 1974
      to 2012. Six trials involving 390 patients were included. RESULTS: TIPS could
      ameliorate refractory ascites on the basis of short-term analysis [odds ratio
      (OR) 8.66; 95% confidence interval (CI), 5.27-14.24] and long-term analysis (OR
      6.07; 95% CI, 3.60-10.22). Hepatic encephalopathy (HE) appeared more common in
      the TIPS arm (OR 2.95; 95% CI, 1.87-4.66). Mortality in the 2 groups did not show
      any difference (OR 0.82; 95% CI, 0.46-1.50). Trial sequential analysis confirmed
      the effect of TIPS upon ascites control and upon the risk of HE recurrence,
      whereas insufficient trials were available to distinguish between the arms on
      mortality. Metaregression analysis showed that the level of urine sodium, serum
      bilirubin, and portal pressure gradient reduction value could be used as survival
      predictors. Subgroup analysis showed an elevated survival effect in TIPS (OR
      0.45; 95% CI, 0.24-0.81), and patients survived longer with recurrent ascites (OR
      0.40; 95% CI, 0.19-0.83). CONCLUSIONS: TIPS was confirmed to improve ascites
      control in both the short term and the long term. Although HE frequently appeared
      in the TIPS group, patients with better hepatic and renal function survived
      longer when they were treated with TIPS. Serum bilirubin and urine sodium could
      be used as pre-TIPS predictors for patient survival. Portal pressure gradient
      reduction values could be used as post-TIPS predictors of survival.

PMID- 24030732
TI  - The complement cascade and renal disease.
AB  - Serum complement cascade, a part of innate immunity required for host protection
      against invading pathogens, is also a mediator of various forms of disease and
      injury. It is activated by classical, lectin, and alternative pathways that lead
      to activation of C3 component by C3 convertases, release of C3b opsonin, C5
      conversion and eventually membrane attack complex formation. The tightly
      regulated activation process yields also C3a and C5a anaphylatoxins, which target
      a broad spectrum of immune and non-immune cells. The review discusses the
      involvement of the complement cascade in kidney disease pathogenesis and injury.
      The role of the complement pathways in autoantibody-mediated forms of
      glomerulonephritis (lupus nephritis, anti-glomerular basement membrane disease,
      anti-neutrophil cytoplasmic autoantibody-induced or membranoproliferative
      glomerulonephritis, membranous nephropathy), C3 glomerulopathy, atypical forms of
      hemolytic uremic syndrome, ischemic-reperfusion injury of transplanted kidney,
      and antibody-mediated renal allograft rejection are discussed. The disturbances
      in complement activation and regulation with underlying genetics are presented
      and related to observed pathology. Also promising strategies targeting the
      complement system in complement-related disorders are mentioned. 

PMID- 24030735
TI  - The establishment of core competencies for canadian genetic counsellors:
      validation of practice based competencies.
AB  - Numerous groups of health professionals have undertaken the task of defining core
      competencies for their profession. The goal of establishing core competencies is
      to have a defined standard for such professional needs as practice guidelines,
      training curricula, certification, continuing competency and re-entry to
      practice. In 2006, the Canadian Association of Genetic Counsellors (CAGC)
      recognized the need for uniform practice standards for the profession in Canada,
      given the rapid progress of genetic knowledge and technologies, the expanding
      practice of genetic counsellors and the increasing demand for services. We report
      here the process by which the CAGC Practice Based Competencies were developed and
      then validated via two survey cycles, the first within the CAGC membership, and
      the second with feedback from external stakeholders. These competencies were
      formally approved in 2012 and describe the integrated skills, attitudes and
      judgment that genetic counsellors in Canada require in order to perform the
      services and duties that fall within the practice of the profession responsibly,
      safely, effectively and ethically. 

PMID- 24030737
TI  - Room temperature C-H bond activation on a [Pd(I)-Pd(I)] platform.
AB  - Heteroatom assisted C-H bond activation of 2-substituted naphthyridines with
      solvated Pd(I)2(CH3CN)6(BF4)2 provides bi- and trinuclear Pd(II) cyclometalated
      complexes, which provide valuable insight into potential intermediates in
      palladium catalyzed direct arylation reactions.

PMID- 24030736
TI  - The clinical and genomic significance of donor-specific antibody-positive/C4d
      negative and donor-specific antibody-negative/C4d-negative transplant
      glomerulopathy.
AB  - BACKGROUND: This study investigated the mechanisms involved in development of
      donor-specific antibody (DSA) and/or C4d-negative transplant glomerulopathy (TGP)
      by allograft gene expression profiles using microarrays. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This cohort study was conducted in kidney
      transplant recipients. Patients were eligible for inclusion if they required a
      clinically indicated biopsy at any time point after their transplant. They were
      then classified according to their histopathology findings and DSA and C4d
      results. Eighteen chronic antibody-mediated rejection (CAMR), 14 DSA+/C4d- TGP,
      25 DSA-/C4d- TGP, and 47 nonspecific interstitial fibrosis/tubular atrophy (IFTA)
      biopsy specimens were identified. In a subset of patients from the study
      population, biopsy specimens in each group and normal transplant kidney specimens
      were analyzed with Affymetrix Human Gene 1.0 ST Arrays. RESULTS: The mean sum
      score of glomerulitis and peritubular capillaritis increased from 0.28+/-0.78 in
      IFTA specimens to 0.75+/-0.85 in DSA-/C4d- TGP specimens, 1.71+/-1.49 in DSA+/C4d
      /TGP specimens, and 2.11+/-1.74 in CAMR specimens (P<0.001). During a median
      follow-up time of 2 (interquartile range, 1.4-2.8) years after biopsy, graft loss
      was highest in CAMR specimens (27.8%) compared to IFTA specimens (8.5%), DSA+/C4d
      TGP specimens (14.3%), and DSA-/C4d- TGP specimens (16%) (P=0.01). With use of
      microarrays, comparison of the gene expression profiles of DSA-/C4d- TGP
      specimens with glomerulitis + peritubular capillaritis scores > 0 to normal and
      IFTA biopsy specimens revealed higher expression of quantitative cytotoxic T cell
      associated transcripts (QCAT). However, both CAMR and DSA+/C4d- TGP specimens had
      higher expression of not only QCAT but also IFN-gamma and rejection-induced,
      constitutive macrophage-associated, natural killer cell-associated, and DSA
      selective transcripts. Endothelial cell-associated transcript expression was
      upregulated only in CAMR biopsy specimens. CONCLUSIONS: These results suggested
      that DSA+/C4d- TGP biopsy specimens may be classified as CAMR. In contrast, DSA
      /C4d- TGP specimens showed increased cytotoxic T cell-associated transcripts,
      suggesting T cell activation as a mechanism of injury.

PMID- 24030739
TI  - Supported employment for adults with severe mental illness.
AB  - BACKGROUND: People who suffer from severe mental disorder experience high rates
      of unemployment. Supported employment is an approach to vocational rehabilitation
      that involves trying to place clients in competitive jobs without any extended
      preparation. The Individual placement and support (IPS) model is a carefully
      specified form of supported employment. OBJECTIVES: 1. To review the
      effectiveness of supported employment compared with other approaches to
      vocational rehabilitation or treatment as usual.2. Secondary objectives were to
      establish how far:(a) fidelity to the IPS model affects the effectiveness of
      supported employment,(b) the effectiveness of supported employment can be
      augmented by the addition of other interventions. SEARCH METHODS: We searched the
      Cochrane Schizophrenia Group Trials Register (February 2010), which is compiled
      by systematic searches of major databases, handsearches and conference
      proceedings. SELECTION CRITERIA: All relevant randomised clinical trials focusing
      on people with severe mental illness, of working age (normally 16 to 70 years),
      where supported employment was compared with other vocational approaches or
      treatment as usual. Outcomes such as days in employment, job stability, global
      state, social functioning, mental state, quality of life, satisfaction and costs
      were sought. DATA COLLECTION AND ANALYSIS: Two review authors (YK and KK)
      independently extracted data. For binary outcomes, we calculated risk ratio (RR)
      and its 95% confidence interval (CI), on an intention-to-treat basis. For
      continuous data, we estimated mean difference (MD) between groups and its 95%
      (CI). We employed a fixed-effect model for analyses. A random-effects model was
      also employed where heterogeneity was present. MAIN RESULTS: A total of 14
      randomised controlled trials were included in this review (total 2265 people). In
      terms of our primary outcome (employment: days in competitive employment, over
      one year follow-up), supported employment seems to significantly increase levels
      of any employment obtained during the course of studies (7 RCTs, n = 951, RR 3.24
      CI 2.17 to 4.82, very low quality of evidence). Supported employment also seems
      to increase length of competitive employment when compared with other vocational
      approaches (1 RCT, n = 204, MD 70.63 CI 43.22 to 94.04, very low quality
      evidence). Supported employment also showed some advantages in other secondary
      outcomes. It appears to increase length (in days) of any form of paid employment
      (2 RCTs, n = 510, MD 84.94 CI 51.99 to 117.89, very low quality evidence) and job
      tenure (weeks) for competitive employment (1 RCT, n = 204, MD 9.86 CI 5.36 to
      14.36, very low quality evidence) and any paid employment (3 RCTs, n = 735, MD
      3.86 CI -2.94 to 22.17, very low quality evidence). Furthermore, one study
      indicated a decreased time to first competitive employment in the long term for
      people in supported employment (1 RCT, n = 204, MD -161.60 CI -225.73 to -97.47,
      very low quality evidence). A large amount of data were considerably skewed, and
      therefore not included in meta-analysis, which makes any meaningful
      interpretation of the vast amount of data very difficult. AUTHORS' CONCLUSIONS:
      The limited available evidence suggests that supported employment is effective in
      improving a number of vocational outcomes relevant to people with severe mental
      illness, though there appears to exist some overall risk of bias in terms of the
      quality of individual studies. All studies should report a standard set of
      vocational and non-vocational outcomes that are relevant to the consumers and
      policy-makers. Studies with longer follow-up should be conducted to answer or
      address the critical question about durability of effects.

PMID- 24030738
TI  - 13-valent pneumococcal conjugate vaccine: a review of its use in infants,
      children, and adolescents.
AB  - The 13-valent pneumococcal conjugate vaccine (Prevenar 13((r)); Prevnar 13((r)))
      [PCV13] includes 13 serotype-specific polysaccharides of Streptococcus pneumoniae
      conjugated individually to non-toxic diphtheria CRM197 protein, thus providing
      wider coverage of pneumococcal serotypes than its 7-valent predecessor (PCV7).
      For pediatric populations, PCV13 was initially approved for use in infants and
      children up to 5 years of age, but recently received approval for expanded use
      (ages 6 weeks to 17 years) in the EU and the USA. This change in labeling was
      made primarily on the basis of results of Study 3011, which demonstrated the
      serotype-specific immunogenicity of a single dose of PCV13 in children >=5 to <10
      years of age who had previously received PCV7. Study 3011 also demonstrated
      functional immune responses after a single dose of PCV13 in a cohort >=10 to <18
      years of age who had not previously received PCV7. Importantly, prior to Study
      3011, several randomized studies comparing PCV13 and PCV7 in infants and younger
      children demonstrated noninferiority of immune responses to the seven serotypes
      common to both vaccines after a two- or three-dose primary infant series and
      after the toddler booster dose; immunogenicity and functional immune responses
      were also demonstrated for the six additional serotypes. The safety and
      reactogenicity of PCV13 was generally similar to that of PCV7, and PCV13 did not
      interfere with the immune responses to coadministered routine pediatric vaccines.
      PCV13 is expected to substantially reduce the incidence of invasive pneumococcal
      diseases in a manner similar to that which occurred after PCV7 was introduced,
      and evidence of the protective effectiveness of PCV13 against pneumococcal
      diseases is emerging.

PMID- 24030740
TI  - Maspin expression and melanoma progression: a matter of sub-cellular
      localization.
AB  - Maspin, a member of the serpin family of protease inhibitors, is involved in key
      processes of cancer progression. Its biological activity seems to be cancer and
      compartment specific, with the protein acting either as a suppressor or as a
      tumor promoter in different cancer types. Characterization of maspin expression
      and its sub-cellular localization in melanoma is missing, hence, we aim to
      investigate its possible association with melanoma prognostic factors and disease
      progression. Nuclear and cytoplasmic maspin expression were evaluated on 60 nevi,
      152 primary lesions, and 106 melanoma metastases using tissue microarrays and
      immunohistochemistry. The association between maspin immunoreactivity and
      patient's clinic-pathological features was evaluated. Multivariate logistic
      models and survival analyses were performed for maspin expression in primary
      melanomas. Nuclear maspin was detected in 8% nevi, 49% primary melanomas, and 28%
      metastases, whereas cytoplasmic maspin in 12% nevi, 18% primary lesions, and 9%
      metastases. In univariate analysis, nuclear maspin expression in primary
      melanomas was significantly associated with melanoma prognostic factors (nodular
      histotype, tumor thickness, mitotic rate, and ulceration) and disease stage,
      whereas cytoplasmic maspin was observed at higher frequency in thin superficial
      spreading melanomas, without mitosis. In multivariate analysis, nuclear maspin
      remained significantly associated with risk of developing a tumor prone to
      disease progression and, accordingly, with significantly shorter disease-free and
      overall survival. In this study, maspin was expressed at highest frequency in
      primary lesions and when expressed in the nuclei, was significantly associated
      with poor prognostic markers, melanoma recurrence, and worse survival. The
      present study suggests a tumor-suppressive effect of cytoplasmic maspin and a
      tumor-promoting effect of nuclear maspin, which open the discussion on its
      potential use in cancer therapy. 

PMID- 24030741
TI  - IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related
      disease.
AB  - IgG4-related disease is a newly described systemic fibroinflammatory process,
      characterized by increase in IgG4-positive plasma cells. Its pathogenesis,
      including the role of IgG4, remains poorly understood. Plasma cell myeloma is
      typically associated with a large monoclonal serum spike, which is frequently of
      IgG isotype. We sought to identify and characterize a subset of IgG4-secreting
      myeloma, as it may provide a biological model of disease with high serum levels
      of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma
      expressed IgG4. Four patients were men and two were women, with a mean age of 64
      (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non
      metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed
      necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2
      g/dl), and none had definite signs or symptoms of IgG4-related disease. Four
      myelomas had plasmablastic morphology. Four had kappa and two had lambda light
      chain expression. Three cases expressed CD56. Two patients had a complex
      karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the
      normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to
      have a high rate of plasmablastic morphology and could be predisposed to
      necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of
      IgG4-related disease. These findings suggest that the increased number of IgG4
      positive plasma cells is not the primary etiologic agent in IgG4-related disease.
      Elevated serum levels of IgG4 is not sufficient to produce the typical disease
      presentation and should not be considered diagnostic of IgG4-related disease. 

PMID- 24030742
TI  - B acute lymphoblastic leukemia with t(14;19)(q32;p13.1) involving IGH/EPOR: a
      clinically aggressive subset of disease.
AB  - B acute lymphoblastic leukemia (B-ALL) with t(14;19)(q32;p13.1), in which IGH and
      EPOR are juxtaposed, has been reported rarely. We describe the
      clinicopathological features of six patients, three men and three women, with a
      median age of 39 years. Initial and follow-up bone marrow samples were examined
      from each patient. The clinical, morphologic, and immunophenotypic results were
      compared with data obtained from conventional cytogenetic analysis and by using
      home-brew fluorescence in situ hybridization (FISH) probes for IGH at 14q32 and
      EPOR at 19p13.1. The bone marrow specimens were hypercellular (median 90%; range
      80-100%), with a median blast count of 90% (range 60-93%). Immunophenotypic
      analysis performed by flow cytometry demonstrated a stable, precursor B-cell
      immunophenotype. The t(14;19)(q32;p13.1) was present in all cases with
      morphologic evidence of disease. The translocation was stable and appeared
      morphologically subtle on conventional karyotypic analysis. Detection was
      facilitated using FISH, which confirmed IGH/EPOR rearrangement in all cases. All
      patients received aggressive multiagent chemotherapy as part of a variety of
      regimens. Four of six patients achieved an initial complete remission, but all
      relapsed. At last follow-up, five of six patients had died of disease (median
      survival, 12 months after diagnosis). We conclude that B-ALL associated with
      t(14;19)(q32;p13.1) is a distinctive form of disease that is associated with
      younger patient age and an aggressive clinical course. 

PMID- 24030743
TI  - Hepatoid adenocarcinoma of the lung: report of five cases and review of the
      literature.
AB  - The current diagnostic criteria for hepatoid adenocarcinoma of lung include
      typical acinar or papillary adenocarcinoma and a component resembling
      hepatocellular carcinoma and expressing alpha-fetoprotein (AFP). Distinguishing
      hepatoid adenocarcinoma of lung from hepatocellular carcinoma metastatic to lung
      is difficult in patients with both lung and liver masses and in patients at risk
      for lung and liver cancer because of smoking and viral hepatitis, respectively.
      We studied morphologic features of hepatoid adenocarcinoma of lung and
      established an immunohistochemical panel to facilitate distinction of hepatoid
      adenocarcinoma of lung from hepatocellular carcinoma metastatic to lung. Five
      cases of hepatoid adenocarcinoma of lung were stained with hematoxylin and eosin
      and mucicarmine for histomorphologic evaluation. The 14-marker
      immunohistochemical profile was established for hepatoid adenocarcinoma of lung
      and compared with that of hepatocellular carcinoma. Two cases of hepatoid
      adenocarcinoma of lung had signet-ring cell components. Three cases were pure
      hepatoid adenocarcinoma without components of acinar or papillary adenocarcinoma,
      signet-ring cells or neuroendocrine carcinoma. Like hepatocellular carcinoma,
      hepatoid adenocarcinoma of lung expresses CK8 (5/5), CK18 (5/5), AFP (3/5) and
      HepPar1 (5/5), shows cytoplasmic staining with TTF-1 (5/5) and does not express
      CK14 (0/5). Unlike hepatocellular carcinoma, it expresses CK5/6 (1/5), CK7 (3/5),
      CK19 (4/5), CK20 (1/5), HEA125 (5/5), MOC31 (5/5), monoclonal CEA (3/5) and
      napsin A (1/5). An immunohistochemical panel that includes a variety of
      cytokeratins, monoclonal CEA and EpCAM markers (HEA125 and MOC31) facilitates
      distinction of hepatoid adenocarcinoma of lung from hepatocellular carcinoma
      metastatic to lung, especially when correlated with clinical and radiologic
      findings. We propose modification of the current diagnostic criteria for hepatoid
      adenocarcinoma of lung. Tumor composition can be either pure hepatoid
      adenocarcinoma or hepatoid adenocarcinoma with components of typical acinar or
      papillary adenocarcinoma, signet-ring cells or neuroendocrine carcinoma. AFP
      expression is not requisite for diagnosis as long as other markers of hepatic
      differentiation are expressed. 

PMID- 24030744
TI  - Fluorescence confocal microscopy for pathologists.
AB  - Confocal microscopy is a non-invasive method of optical imaging that may provide
      microscopic images of untreated tissue that correspond almost perfectly to
      hematoxylin- and eosin-stained slides. Nowadays, following two confocal imaging
      systems are available: (1) reflectance confocal microscopy, based on the natural
      differences in refractive indices of subcellular structures within the tissues;
      (2) fluorescence confocal microscopy, based on the use of fluorochromes, such as
      acridine orange, to increase the contrast epithelium-stroma. In clinical practice
      to date, confocal microscopy has been used with the goal of obviating the need
      for excision biopsies, thereby reducing the need for pathological examination.
      The aim of our study was to test fluorescence confocal microscopy on different
      types of surgical specimens, specifically breast, lymph node, thyroid, and colon.
      The confocal images were correlated to the corresponding histological sections in
      order to provide a morphologic parallel and to highlight current limitations and
      possible applications of this technology for surgical pathology practice. As a
      result, neoplastic tissues were easily distinguishable from normal structures and
      reactive processes such as fibrosis; the use of fluorescence enhanced contrast
      and image quality in confocal microscopy without compromising final histologic
      evaluation. Finally, the fluorescence confocal microscopy images of the adipose
      tissue were as accurate as those of conventional histology and were devoid of the
      frozen-section-related artefacts that can compromise intraoperative evaluation.
      Despite some limitations mainly related to black/white images, which require
      training in imaging interpretation, this study confirms that fluorescence
      confocal microscopy may represent an alternative to frozen sections in the
      assessment of margin status in selected settings or when the conservation of the
      specimen is crucial. This is the first study to employ fluorescent confocal
      microscopy on surgical specimens other than the skin and to evaluate the
      diagnostic capability of this technology from pathologists' viewpoint. 

PMID- 24030745
TI  - High-risk human papillomavirus is transcriptionally active in a subset of
      sinonasal squamous cell carcinomas.
AB  - It has been reported that high-risk human papillomavirus (HPV) is a causative
      agent of a subgroup of oropharyngeal carcinomas. In these tumors, the presence of
      the transcriptionally active HPV has been proved through the identification of
      HPV E6 or E7 messenger RNA (mRNA) transcripts. The aim of the study was to assess
      the HPV-active transcription in a series of sinonasal carcinomas, in correlation
      with the HPV DNA identification and the p16 immunohistochemistry. Seventy
      patients with squamous cell carcinomas of the sinonasal tract were included in
      the survey. The main clinicopathological characteristics were recorded. All
      tumors were investigated for HPV through the HPV DNA detection by PCR, using the
      SPF10 primers and by in situ hybridization, using the high-risk GenPoint probe
      (Dako, Glostrup, Denmark). HPV16 E7 mRNA transcripts detection was performed by
      RT-PCR in 27 cases. The immunostaining for p16 was performed in all cases.
      Fourteen carcinomas (20%) were positive for high-risk HPV by PCR: 13 HPV16 and
      one HPV35. In situ hybridization showed a dotted nuclear positivity in all these
      cases. HPV16 E7 mRNA was detected in seven tumors harboring HPV16; in the
      remaining HPV-positive cases, RNA did not reach the quality for analysis. Strong,
      diffuse positivity for p16 was observed only in the HPV-positive cases. The 14
      HPV-positive squamous cell carcinomas were non-keratinizing or scarcely
      keratinizing tumors. No significant differences were found in terms of gender,
      age, or staging at diagnosis between HPV-positive and HPV-negative tumors.
      However, differences in disease-free survival and overall survival between both
      groups of patients were significant (P=0.004 and P=0.028, respectively). In
      conclusion, we have shown that HPV is the etiological agent of a subset of
      sinonasal carcinomas demonstrating the transcriptionally active HPV in these
      tumors. Immunostaining for p16 can be used as a surrogate marker to identify
      these tumors. 

PMID- 24030746
TI  - Multiple genetic alterations in primary cutaneous large B-cell lymphoma, leg type
      support a common lymphomagenesis with activated B-cell-like diffuse large B-cell
      lymphoma.
AB  - Primary cutaneous large B-cell lymphoma, leg type has been individualized from
      nodal diffuse large B-cell lymphoma. The objective of this study was to screen
      primary cutaneous large B-cell lymphoma, leg type for genetic alterations
      recently described in nodal diffuse large B-cell lymphoma. Skin biopsies from 23
      patients were analyzed for IRF4, BCL2, BCL6, and MYC expression. FISH testing was
      performed for BCL2, BCL6, MYC with separation probes and for CDKN2A and
      PRDM1/BLIMP1 deletion. Multiple sequential FISH analyses with up to six probes
      were performed to define samples with multiple cytogenetic alterations. MYD88
      mutations were studied by Sanger sequencing. All cases but one displayed at least
      one genetic alteration (96%). Nine patients exhibited a single genetic mutation
      and 12 combined several alterations (52%). We observed a split for BCL2, BCL6, or
      MYC in 1/23, 6/23, and 3/23 of cases, respectively. No double-hit lymphoma was
      observed. CDKN2A deletion was detected by FISH in only 5/23 cases. BLIMP1 and/or
      6q deletion was observed at a higher rate in 10/20 of cases. No correlation
      between rearrangement and immunohistochemical expression was found for BCL2 or
      MYC. FISH tracking of sequential hybridizations showed that several alterations
      were carried by the same nuclei. The p.L265P MYD88 mutation was found in 11/18
      (61%) of cases. Contrary to most cutaneous lymphomas that rarely harbor primary
      genetic alteration of their nodal histological equivalent, primary cutaneous
      large B-cell lymphoma, leg type seems to be a 'cutaneous counterpart' of
      activated B-cell-like diffuse large B-cell lymphoma with a similar cytogenetic
      profile and a high rate of MYD88 oncogenic L265P mutation. This also suggests a
      common lymphomagenesis with NF-kappaB activation, strong IRF4 expression and
      terminal B-cell differentiation blockage. Our data support the use of therapies
      targeting NF-kappaB, as most patients displayed disease progression and
      resistance to conventional therapies. 

PMID- 24030747
TI  - Nuclear expression of STAT6 distinguishes solitary fibrous tumor from histologic
      mimics.
AB  - Solitary fibrous tumor (SFT) is composed of spindled to ovoid cells in a
      patternless architecture with prominent stromal collagen and hemangiopericytoma
      like vessels. Some tumors show hypercellularity, nuclear atypia, and significant
      mitotic activity; the latter feature in particular often portends an aggressive
      clinical course. SFT can sometimes be difficult to distinguish from other benign
      mesenchymal tumors and sarcomas. The most characteristic (albeit nonspecific)
      immunohistochemical finding in SFT is CD34 expression. A NAB2-STAT6 gene fusion,
      resulting in a chimeric protein in which a repressor domain of NGFI-A binding
      protein 2 (EGR1 binding protein 2) (NAB2) is replaced with a carboxy-terminal
      transactivation domain from signal transducer and activator of transcription 6,
      interleukin-4 induced (STAT6), was recently identified as a consistent finding in
      SFT. However, as these genes are located in close proximity on 12q13, this fusion
      can only rarely be detected by conventional chromosomal banding or fluorescence
      in situ hybridization analysis. Nuclear expression of the carboxy terminal part
      of STAT6 is a consistent finding in SFT of the meninges (so-called 'meningeal
      hemangiopericytoma'). We investigated STAT6 expression by immunohistochemistry in
      SFTs and other soft tissue tumors arising outside the central nervous system to
      validate the diagnostic utility of this novel marker. Whole-tissue sections of
      231 tumors were evaluated, including 60 cases of SFT as well as other benign and
      malignant mesenchymal neoplasms and sarcomatoid mesotheliomas. Fifty-nine of 60
      SFT cases (98%) showed nuclear expression of STAT6, which was usually diffuse and
      intense. All other tumor types were negative for STAT6, except for three
      dedifferentiated liposarcomas and one deep fibrous histiocytoma, which showed
      weak staining. In conclusion, STAT6 is a highly sensitive and almost perfectly
      specific immunohistochemical marker for SFT and can be helpful to distinguish
      this tumor type from histologic mimics. 

PMID- 24030748
TI  - Loss of CIC and FUBP1 expressions are potential markers of shorter time to
      recurrence in oligodendroglial tumors.
AB  - Combined deletion of chromosomes 1p and 19q is a prognostic marker in
      oligodendroglial tumors. Recent studies in oligodendroglial tumors have unveiled
      recurrent mutations of CIC (homolog of Drosophila capicua) and FUBP1 (far
      upstream element binding protein 1) that are located on 19q13 and 1p31,
      respectively. However, the impact of CIC and FUBP1 mutations on their protein
      expressions has not been examined. The aims of this study were to correlate the
      expression patterns of CIC and FUBP1 with their mutation profiles and to evaluate
      the clinical relevance of these molecular markers in 55 oligodendroglial tumors
      diagnosed in 47 adult patients. Using direct sequencing, somatic mutations of CIC
      and FUBP1 were identified in 47% (22/47) and 16% (7/45) of oligodendroglial
      tumors, respectively. Immunohistochemical analysis revealed loss of CIC or FUBP1
      protein expression in 36% (20/55) and 16% (9/55) of oligodendroglial tumors
      examined. Somatic mutation was significantly associated with absent protein
      expression for both genes (CIC, P=0.01; FUBP1, P=0.00001). Four tumors with
      undetectable CIC mutations exhibited absent CIC expression, suggesting that CIC
      inactivation could be mediated by mechanisms other than mutations and genomic
      loss. Univariate survival analysis revealed that 1p/19q codeletion was
      significantly associated with overall survival (P=0.05). Loss of CIC expression
      was significantly correlated with shorter progression-free survival (P=0.03),
      whereas CIC alteration (mutation or null expression) with worse overall survival
      (P=0.05). Absent FUBP1 expression was linked with unfavorable progression-free
      survival (P=0.02) and overall survival (P=0.01). In 16 tumors with 1p/19q
      codeletion, CIC mutation was associated with unfavorable survival (P=0.01). There
      was a correlation between lack of CIC or FUBP1 expression and poor progression
      free survival (P=0.004; P=0.0003). No molecular markers showed association with
      survival in oligodendroglial tumors lacking 1p/19q codeletion. We conclude that
      absent CIC and FUBP1 expressions are potential markers of shorter time to
      recurrence and CIC mutation a potential marker of worse prognosis, especially in
      tumors carrying 1p/19q codeletion. 

PMID- 24030749
TI  - Nestin expression is associated with aggressive cutaneous melanoma of the nodular
      type.
AB  - The intermediate filament nestin, a neural stem-cell marker, is reported to be
      expressed more strongly in melanomas compared with benign melanocytic lesions,
      and increasingly expressed in advanced melanoma stages. However, the prognostic
      impact of nestin on melanoma has not been well elucidated. The aim of the present
      study was to evaluate the prognostic influence of nestin expression in cutaneous
      melanoma in comparison with standard clinico-pathologic variables. In a large
      series of nodular cutaneous melanoma (n=348), nestin expression was assessed by
      immunohistochemistry using tissue microarray (TMA) sections. For comparison,
      nestin staining in corresponding metastases as well as in superficial spreading
      melanomas and benign nevi was also examined. Nestin was expressed to varying
      degrees in a majority of nodular melanomas (92%), and was significantly
      associated with increased tumor thickness, high mitotic count, and the presence
      of ulceration and tumor necrosis. Also, expression was stronger in the nodular
      type than in superficial spreading melanomas and benign nevi, but without
      significant difference when compared with matched metastases from the former.
      Importantly, strong expression of nestin was significantly associated with
      reduced survival in multivariate analysis. In conclusion, increased nestin
      expression was associated with aggressive melanoma features, with independent
      prognostic impact on multivariate survival analysis when compared with clinico
      pathologic factors. 

PMID- 24030750
TI  - TERT promoter mutations are frequent in atypical fibroxanthomas and pleomorphic
      dermal sarcomas.
AB  - Activating mutations in the TERT promoter leading to increased telomerase
      expression were recently identified in cutaneous melanoma and subsequently in
      many other types of cancer. These mutations lead to increased telomerase
      expression, allowing cells to proliferate continuously without entering apoptosis
      or senescence. Atypical fibroxanthomas and pleomorphic dermal sarcomas are
      genetically poorly understood tumors developing in the skin of older patients.
      Known genetic events in these tumors are mutations in TP53 (atypical
      fibroxanthoma and pleomorphic dermal sarcoma) and RAS (pleomorphic dermal
      sarcoma) genes, often having a UV signature. We analyzed a cohort of 27 atypical
      fibroxanthomas and 34 pleomorphic dermal sarcomas for the presence of TERT
      promoter mutations by conventional Sanger sequencing. TERT promoter mutations
      were identified in 25 (93%) atypical fibroxanthomas and in 26 (76%) pleomorphic
      dermal sarcomas. Mutations were found to have a UV signature (C>T or CC>TT) and
      were largely identical to those detected in cutaneous melanoma. Our data show
      that TERT promoter mutations are the most frequent mutations in atypical
      fibroxanthomas and pleomorphic dermal sarcomas reported to date. The identified
      mutations confirm the pathogenetic role of UV exposure in both atypical
      fibroxanthomas and pleomorphic dermal sarcomas and suggest that telomere
      maintenance through increased expression of telomerase plays an important role in
      the pathogenesis of these tumors. 

PMID- 24030751
TI  - Expression status of wild-type HSP110 correlates with HSP110 T17 deletion size
      and patient prognosis in microsatellite-unstable colorectal cancer.
AB  - It has been recently suggested that the expression levels of mutant HSP110 could
      be a prognostic marker in colorectal cancer with a high level of microsatellite
      instability (MSI-H). The aim of our study was to validate the prognostic
      significance of HSP110 mutation using immunohistochemistry and DNA testing in MSI
      H colorectal cancer. Wild-type HSP110 (HSP110wt)-specific immunohistochemistry
      was performed in 168 MSI-H colorectal cancer tissues, and their expression levels
      were evaluated using a four-tier scoring system (0/1+/2+/3+). Of these tissues,
      167 cases were analyzed for HSP110 T17 deletion. Associations with
      clinicopathological, molecular and survival parameters were statistically
      analyzed. The low-level expression of HSP110wt (0/1+) was observed in 40 MSI-H
      colorectal cancers (24%) and was significantly related to large HSP110 T17
      deletions (>= 4 bp, P<0.001). In survival analysis, patients with low HSP110wt
      expression (0/1+) showed better disease-free survival compared with those with
      high expression (2+/3+; P=0.005). This significance in survival difference was
      maintained in patients with 5-fluorouracil-based chemotherapy-treated tumors
      (P=0.024) and in those with stage III/IV tumors (P=0.032). Multivariate analysis
      confirmed the role of HSP110wt expression as an independent prognostic factor
      (P=0.016, hazard ratio=4.32). In MSI-H colorectal cancer, a low expression of
      HSP110wt is associated with large HSP110 T17 deletions and better clinical
      outcome. Immunohistochemistry of HSP110wt can be a simple and valuable tool for
      the prognostic and therapeutic stratification of patients with MSI-H colorectal
      cancer. 

PMID- 24030752
TI  - Mutations of the TERT promoter are common in basal cell carcinoma and squamous
      cell carcinoma.
AB  - Telomerase is frequently expressed in cancer and contributes to carcinogenesis.
      Two recent publications report the identification of a set of recurrent mutations
      in melanoma in the promoter of the telomerase reverse transcriptase gene (TERT)
      that appears to be the result of mutagenesis from ultraviolet (UV) radiation.
      Both groups reported that the mutations increase the transcription of TERT. This
      prompted our search for similar mutations in two other UV-related skin cancers,
      basal cell carcinoma, and squamous cell carcinoma. We found that the activating
      TERT promoter mutations reported in melanoma are also frequent in squamous cell
      carcinoma (50%) and basal cell carcinoma, the latter including both sporadic
      tumors (78%) and tumors from patients with nevoid basal cell carcinoma syndrome
      (68%). These mutations were found in only 1 of 11 Bowen's disease (squamous cell
      carcinoma in situ) specimens, and in none of 15 non-malignant skin specimens and
      57 blood specimens. The mutations were frequently homozygous or hemizygous, with
      little or no normal signal at the mutated positions. These data suggest that TERT
      promoter mutations are the most frequent putative oncogenic mutations in
      cutaneous cancer. 

PMID- 24030753
TI  - Incidence and prognostic value of bleeding after percutaneous coronary
      intervention in patients older than 75 years of age.
AB  - OBJECTIVES: We aimed to assess the impact of bleeding after percutaneous coronary
      intervention (PCI) on the outcome of patients >75 years of age. BACKGROUND:
      Limited information exists on the impact of post-PCI bleeding on the outcome in
      elderly patients. METHODS: This study included 3,255 patients >75 years of age.
      Bleeding events were assessed using the Bleeding Academic Research Consortium
      (BARC) criteria. The primary outcome was 1-year mortality. RESULTS: Within 30
      days after PCI, bleeding occurred in 501 patients (15.4%). Bleeding according to
      BARC was: class 1 (170 patients; 33.9%), class 2 (81 patients; 16.2%), class 3a
      (177 patients; 35.3%), class 3b (65 patients; 13.0%), class 3c (four patients;
      0.8%), and class 4 (four patients; 0.8%). There were 201 deaths within the first
      year after PCI: 61 deaths (12.3%) among bleeders and 140 deaths (5.1%) among
      nonbleeders (adjusted hazard ratio = 2.03, 95% confidence interval [CI] 1.42
      2.91, P < 0.001). Bleeding improved the discriminatory power of multivariable
      model for mortality prediction (P = 0.001). Female sex (adjusted odds ratio [OR]
      = 1.49 [1.17-1.88], P = 0.001) and reduced renal function (adjusted OR = 1.30
      [1.04-1.63], P = 0.019 for each 30 ml/min decrease in the creatinine clearance)
      were independent associates of increased bleeding risk. Bivalirudin reduced the
      bleeding risk by 24% compared with unfractionated heparin and 33% compared with
      abciximab plus unfractionated heparin. CONCLUSIONS: Post-PCI bleeding is an
      important prognostic factor in patients >75 years of age. The risk for bleeding
      in this age category is increased in women and patients with impaired renal
      function. Bleeding risk is reduced by bivalirudin.

PMID- 24030754
TI  - Using the C7-T3 spinous processes as landmarks for the localization of thoracic
      spinal lesions: technique notes.
AB  - The authors describe a method of using the C7-T3 spinous processes visualized on
      MRI as landmarks for localizing thoracic spinal lesions in 19 cases. This method
      included six steps. First, the "spinous process nearest to the lesion that was
      visible on the MRI image" was identified. Second, a dashed line was drawn on the
      image through the tip of the identified spinous process perpendicular to the skin
      surface. Third, two additional dashed lines parallel to the first dashed line
      were drawn from the upper and lower margins of the lesion. Fourth, the distances
      between the identified process and the two additional dashed lines were measured.
      Fifth, the same "spinous process nearest to the lesion" was identified by
      palpation and marked on the patient's skin. Sixth, the upper and lower margins of
      the lesion were marked on the skin according to the two distances measured in
      step 4. After the lesion was exposed, the deviations of the lesion margins were
      measured. All 19 cases of the thoracic spinal lesions were localized correctly
      using the C7-T3 spinous processes visualized on the MRI images as landmarks
      without any other evaluation methods. The deviation value for the localization of
      the tumor margin was 4.1 +/- 1.47 mm. Using the C7-T3 spinous processes as
      landmarks is an accurate, simple, and economic method for lesion localization
      during thoracic spinal surgery. 

PMID- 24030755
TI  - An anatomical variant of the deep inferior epigastric perforator vein.

PMID- 24030756
TI  - Synthesis of gem-difluorocyclopropa(e)nes and O-, S-, N-, and P
      difluoromethylated compounds with TMSCF(2)Br.
AB  - Two-in-one: Me3 SiCF2 Br is an efficient difluorocarbene source and is compatible
      with both neutral and aqueous basic conditions. Bromide-ion-initiated [2+1]
      cycloaddition with alkenes/alkynes and hydroxide ion promoted alpha-addition with
      (thio)phenols, (thio)alcohols, sulfinates, heterocyclic amines, and H-phosphine
      oxides give the corresponding gem-difluorinated compounds with broad functional
      group tolerance. 

PMID- 24030757
TI  - Predictors of persistent sleep apnea after surgery in children younger than 3
      years.
AB  - IMPORTANCE: Obstructive sleep apnea (OSA) is a common disorder in children and
      can lead to important sequelae. Predictors of persistent OSA after
      adenotonsillectomy (T&A) in younger children are not well studied. OBJECTIVE: To
      evaluate residual OSA in a subgroup of children younger than 3 years after T&A
      and identify predictors of postoperative residual disease. DESIGN, SETTING, AND
      PARTICIPANTS Retrospective review of medical records at a tertiary academic
      children's hospital involving children younger than 3 years who had OSA
      documented by polysomnogram(PSG) and underwent T&A during the period October 1,
      2002, through June 30, 2010. Some of these children had both preoperative and
      postoperative PSGs. MAIN OUTCOMES AND MEASURES Effect of T&A on sleep study
      parameters and predictors of persistent disease after surgery. RESULTS A total of
      283 patients (mean [SD] age, 22 [7] months) underwent a preoperative PSG, with 70
      of these patients having both a preoperative and postoperative PSG. In the group
      who had preoperative and postoperative PSGs, there were statistically significant
      improvements in mean (SD) apnea hypopnea index (AHI) (34.8 [40.7] to 5.7 [13.8];
      P < .001), baseline oxygen saturation (96.6%[2.1%] to 97.2%[1.4%]; P = .05),
      minimum oxygen saturation (77.2%[11.4%] to 89.9%[6.8%]; P < .001), and sleep
      efficiency (84.7%[14.9%] to 88.7%[9.1%]; P = .02) after T&A. When AHI greater
      than 5 was used as the definition of OSA, 21% of the patients (15 of 70) had
      residual OSA. The most consistent predictor of residual OSA after T&A was the
      severity of preoperative OSA (P = .02). CONCLUSIONS AND RELEVANCE In a subgroup
      of children younger than 3 years with OSA, we found a high rate of residual OSA
      after T&A. Predictors of residual disease include severity of preoperative OSA as
      determined by PSG result. Postoperative PSGs might be indicated in these
      patients.

PMID- 24030761
TI  - Syncope: a tale of two triggers.

PMID- 24030758
TI  - Trypsin causes platelet activation independently of known protease-activated
      receptors.
AB  - To identify a physiological agonist of PAR3, we used PAR4 null murine platelets,
      which were known to express only PAR3. In this study, we tested several proteases
      and found that trypsin, but not heat-inactivated trypsin, activated PAR4 null
      murine platelets. Even at high concentrations, trypsin caused shape change
      without increasing intracellular calcium levels in PAR4 null murine platelets.
      Consistent with this result, the Gq inhibitor YM-254890 had no effect on trypsin
      induced shape change. However, trypsin-induced platelet shape change was
      abolished by either p160ROCK inhibitor, Y27632 or H1152. Furthermore, trypsin
      caused phosphorylation of myosin light chain (Thr18), but not Akt or Erk.
      Surprisingly, trypsin caused a similar shape change in PAR4-desensitised PAR3
      null murine platelets as in PAR4null murine platelets, indicating that trypsin
      did not activate PAR3 to cause shape change. More interestingly, the Src family
      kinase (SFK) inhibitor PP2 abolished trypsin-induced, but not AYPGKF-induced,
      shape change. Hence, trypsin activated a novel signalling pathway through
      RhoA/p160ROCK and was regulated by SFKs. In conclusion, our study demonstrates a
      novel protease signalling pathway in platelets that is independent of PARs. This
      protease-induced novel signalling pathway regulates platelet shape change through
      SFKs and p160ROCK. 

PMID- 24030762
TI  - Patient preferences for deactivation of implantable cardioverter-defibrillators.

PMID- 24030763
TI  - A different point of view on sex and risk of hip implant failure and failure rate
      in women.

PMID- 24030764
TI  - A different point of view on sex and risk of hip implant failure and failure rate
      in women.

PMID- 24030765
TI  - A different point of view on sex and risk of hip implant failure and failure rate
      in women--reply.

PMID- 24030766
TI  - Harmful effects of proton pump inhibitors: discrepancies between observational
      studies and randomized clinical trials.

PMID- 24030767
TI  - Harmful effects of proton pump inhibitors: discrepancies between observational
      studies and randomized clinical trials--reply.

PMID- 24030770
TI  - Impact of prenatal diagnosis of ductal origin of the left pulmonary artery.

PMID- 24030769
TI  - Evaluation of expression of the PTEN gene, oestrogen and progesterone receptors
      as diagnostic and predictive factors in endometrial cancer.
AB  - Endometrial cancer belongs to the commonest malignancy in females after breast
      cancer, malignant neoplasm of female genitals in Europe and North America but
      there is still not significant improvement as far as the curability of this
      neoplasm is concerned, especially its advanced forms. That is why there is need
      to define new factors that could be not only diagnostic but also predictve
      factors. In present study we analyzed the mRNA PTEN expression by quantitative
      real-time polymerase chain reaction (Q-PCR) in 123 women of endometrial carcinoma
      and 14 women of control group. Moreover we assessed oestrogen (ER) and
      progesterone receptors (PgR) in all cases. We defined the correlation between
      expression of PTEN gene and receptors and between PTEN expression and maturity
      grade of cancer. Neoplasm advancement grade G1 was diagnosed in 82.11% of
      patients (n = 101), G2 in 9.76% of patients (n = 12) and G3 in 8.13% of patients
      (n = 10). Presence of ER and PgR and decreased expression of PTEN gene was found
      in majority of patients with endometrial cancer (79.12% and 59.34% respectively)
      and the most numerous group was with weak expression of ER and strong expression
      of PgR. There was no statistically significant difference in gene expression
      depending on receptors expression nor maturity grade of cancer (p > 0.05).
      Evaluation of expression of PTEN gene may turn out to be a very useful tool aimed
      at qualifying patients for different therapies of endometrial cancer and at
      searching of new diagnostic and therapeutic methods of this cancer independently
      on its receptor status nor maturity grade of cancer.

PMID- 24030771
TI  - Molecular farming in tobacco hairy roots by triggering the secretion of a
      pharmaceutical antibody.
AB  - Recombinant pharmaceutical proteins expressed in hairy root cultures can be
      secreted into the medium to improve product homogeneity and to facilitate
      purification, although this may result in significant degradation if the protein
      is inherently unstable or particularly susceptible to proteases. To address these
      challenges, we used a design of experiments approach to develop an optimized
      induction protocol for the cultivation of tobacco hairy roots secreting the full
      size monoclonal antibody M12. The antibody yield was enhanced 30-fold by the
      addition of 14 g/L KNO3 , 19 mg/L 1-naphthaleneacetic acid and 1.5 g/L of the
      stabilizing agent polyvinylpyrrolidone. Analysis of hairy root cross sections
      revealed that the optimized medium induced lateral root formation and
      morphological changes in the inner cortex and pericycle cells, indicating that
      the improved productivity was at least partially based on the enhanced efficiency
      of antibody secretion. We found that 57% of the antibody was secreted, yielding
      5.9 mg of product per liter of induction medium. Both the secreted and
      intracellular forms of the antibody could be isolated by protein A affinity
      chromatography and their functionality was confirmed using vitronectin-binding
      assays. Glycan analysis revealed three major plant complex-type glycans on both
      forms of the antibody, although the secreted form was more homogeneous due to the
      predominance of a specific glycoform. Tobacco hairy root cultures therefore offer
      a practical solution for the production of homogeneous pharmaceutical antibodies
      in containment.

PMID- 24030772
TI  - The role of working memory and divided attention in metaphor interpretation.
AB  - Although several types of figurative language exist, neuropsychological tests of
      non-literal language have focused on proverbs. Metaphors in the form X is (a) Y
      (e.g., The body's immunological response is a battle against disease.) place a
      lower demand on language skills and are more easily manipulated for novelty than
      proverbs. Forty healthy participants completed the Metaphor Interpretation Test
      (developed by the authors). The task includes 20 items chosen from a list of
      metaphors that were rated on several scales (e.g. imagery, aptness) in a study by
      Katz et al. (Metaphor Symb Act 3(4):191-214, 1988). Participants were asked to
      rate the familiarity and provide an explanation of each metaphor. A scoring
      system was developed to categorize answers into: abstract complete (AC), abstract
      partial (AP), concrete (CT), and other/unrelated (OT) types. Participants also
      completed short-term memory and divided attention tests. Overall, participants
      produced 56 % AC, 25.38 % AP, 7.88 % CT, and 10.88 % OT responses. It was found
      that a measure of verbal short-term memory span was the best predictor of
      performance on this task (adjusted R(2) = .369). It appears that short-term
      memory span, not working memory or divided attention, contributes most to
      providing abstract responses in explaining metaphors. This is in line with the
      idea that when one accesses the semantic network associated with a novel
      metaphor, one must hold this information in mind long enough to search for and
      link similar cognitive networks.

PMID- 24030773
TI  - Assessing L2 lexical versus inflectional accuracy across skill levels.
AB  - This study measures whether number and type of morphemes in an elicited imitation
      string results in a greater number of modifications with L2 experience. Rationale
      is drawn from L2 working memory processing limitations at distinct levels of
      proficiency. 38 subjects (L2 Spanish university students) comprise three
      proficiency groups: beginning, undergraduate majors and graduate students. Number
      of morphemes was varied within each syllable count; and responses were either
      correct or modified (lexemically/inflectionally as deletions or substitutions).
      Two way ANOVAs determined significance between mean proportions for each group.
      Findings indicate that increases in number of morphemes yielded significant
      differences; and that while the lowest proficiency group produced higher
      proportions of lexical deletions, the more advanced groups' modifications were
      inflectional substitutions. 

PMID- 24030774
TI  - Which form is that? The importance of selenium speciation and metabolism in the
      prevention and treatment of disease.
AB  - The biological activity of selenium is dependent upon its speciation. We aim to
      integrate selenium speciation and metabolism into a discussion of the mechanisms
      by which selenium exerts its biological activity. First, we present the current
      status of selenium in the prevention of cancer, cardiovascular and
      neurodegenerative diseases with particular attention paid to the results of major
      chemoprevention trials involving selenium supplementation. A comprehensive review
      of the current understanding of the metabolism of common dietary selenium
      compounds - selenite, selenomethionine, methylselenocysteine and selenocystine -
      is presented, with discussion of the evidence for the various metabolic pathways
      and their products. The antioxidant, prooxidant and other mechanisms of the
      dietary selenium compounds have been linked to their disease prevention and
      treatment properties. The evidence for these various mechanisms -in vitro, in
      cells and in vivo- is evaluated with emphasis on the selenium metabolites
      involved. We conclude that dietary selenium compounds should be considered
      prodrugs, whose biological activity will depend on the activity of the various
      metabolic pathways in, and the redox status of, cells and tissues. These factors
      should be considered in future laboratory research and in selecting selenium
      compounds for trials of disease prevention and treatment by selenium
      supplementation. 

PMID- 24030776
TI  - Enantioselective reactions of N-acyliminium ions using chiral organocatalysts.
AB  - N-acyliminium ions are reactive intermediates that can act as electron-deficient
      electrophiles toward weak or soft nucleophiles, thereby providing useful methods
      for both intermolecular- and intramolecular carbon-carbon and carbon-heteroatom
      bond formation. Nucleophilic additions to N-acyliminium ions constitute an
      important method for providing alpha-functionalized amino compounds and many
      other biologically active nitrogen-containing heterocycles. The development of
      efficient catalytic asymmetric reactions is a key objective in modern organic
      chemistry and is very important for the synthesis of natural products,
      pharmaceuticals, and agrochemicals. Various methods are available for this
      purpose and mostly rely on the use of chiral catalysts for enantioselective
      synthesis. This review deals with one aspect of such catalysis, which has emerged
      only in the past few years, and its applications in enantioselective reactions of
      N-acyliminium ions to provide various nitrogen-containing heterocycles. 

PMID- 24030777
TI  - International, interdisciplinary, multi-level bioinformatics training and
      education.

PMID- 24030775
TI  - The aryl hydrocarbon receptor in innate T cell immunity.
AB  - Recent studies highlight an important role of the aryl hydrocarbon receptor (AhR)
      at mucosal barriers. Surprisingly, activation of the AhR, required for the
      maintenance of lymphocytes as well as lymphoid architecture, can be achieved via
      cues derived from the external environment. This environment contains both
      beneficial and harmful microorganisms as well as a diverse array of compounds,
      and the epithelia must offer very sophisticated levels of defence. This is
      achieved via multifaceted immune recognition diversity and cellular complexity.
      Mucosal associated tissues, particularly in the gastrointestinal tract,
      constitute a complex immune organ for local lymphocytes and contain highly
      organised lymphoid structures. We will discuss the recent observations concerning
      the AhR in relation to the function and maintenance of innate T cells, with focus
      on gammadelta T cells found enriched at epithelial barriers. 

PMID- 24030778
TI  - Growth of large-scale boron nanowire patterns with identical base-up mode and in
      situ field emission studies of individual boron nanowire.
AB  - Boron nanowires (BNWs) are considered as an ideal optoelectronic nanomaterial,
      but controlling them in identical growth mode and large-area patterns is
      technically challenging. Here, large-scale BNW patterns with a uniform base-up
      growth mode are successfully fabricated by choosing Ni film as the catalyst.
      Moreover, they exhibit low turn-on field (4.3 V/MUm) and excellent field emission
      uniformity (88%). 

PMID- 24030779
TI  - Duward F. Shriver (1934-2013).

PMID- 24030780
TI  - Postclose technique for large sheath arterial access using perclose(TM) in
      emergency endovascular repair.
AB  - The "Preclose technique" using a perclose device has recently become widely used
      in various percutaneous procedures requiring a large access sheath. However, the
      post-procedural application of the perclose(TM) to the large sheath arteriotomy
      is more challenging because of the risk of bleeding and difficulty of device
      application. This report introduces a novel post-procedural closing technique of
      large 22 Fr arterial sheath access using perclose devices.

PMID- 24030781
TI  - IQdb: an intelligence quotient score-associated gene resource for human
      intelligence.
AB  - Intelligence quotient (IQ) is the most widely used phenotype to characterize
      human cognitive abilities. Recent advances in studies on human intelligence have
      identified many new susceptibility genes. However, the genetic mechanisms
      involved in IQ score and the relationship between IQ score and the risk of mental
      disorders have won little attention. To address the genetic complexity of IQ
      score, we have developed IQdb (http://IQdb.cbi.pku.edu.cn), a publicly available
      database for exploring IQ-associated human genes. In total, we collected 158
      experimental verified genes from literature as a core dataset in IQdb. In
      addition, 46 genomic regions related to IQ score have been curated from
      literature. Based on the core dataset and 46 confirmed linked genomic regions,
      more than 6932 potential IQ-related genes are expanded using data of protein
      protein interactions. A systematic gene ranking approach was applied to all the
      collected and expanded genes to represent the relative importance of all the 7090
      genes in IQdb. Our further systematic pathway analysis reveals that IQ-associated
      genes are significantly enriched in multiple signal events, especially related to
      cognitive systems. Of the 158 genes in the core dataset, 81 are involved in
      various psychotic and mental disorders. This comprehensive gene resource
      illustrates the importance of IQdb to our understanding on human intelligence,
      and highlights the utility of IQdb for elucidating the functions of IQ-associated
      genes and the cross-talk mechanisms among cognition-related pathways in some
      mental disorders for community. Database URL: http://IQdb.cbi.pku.edu.cn. 

PMID- 24030782
TI  - Intravenous lidocaine for post-operative pain relief after hand-assisted
      laparoscopic colon surgery: a randomized, placebo-controlled clinical trial.
AB  - BACKGROUND: Perioperative intravenous (IV) infusion of lidocaine has been shown
      to decrease post-operative pain, shorten time to return of bowel function, and
      reduce the length of hospital stay. This randomized, prospective, double-blinded,
      placebo-controlled clinical trial evaluated the impact of IV lidocaine on the
      quality of post-operative analgesia and other outcomes after hand-assisted
      laparoscopic colon surgery. METHODS: Sixty four patients with colon cancer
      scheduled for elective colon resection were involved in this study. Patients were
      randomized to receive either lidocaine infusion [lidocaine group (LG)] or normal
      0.9 % saline infusion [placebo group (PG)] for a period of 24 h. Anaesthetic and
      surgical techniques were standardized. Twenty-four-hour post-operative analgesia
      in the recovery area was maintained by continuous infusion of 0.1 MUg/kg/h
      fentanyl. The primary outcome of the study was post-operative pain control. Pain
      was assessed using visual analogue scale (VAS) scores at 2, 4, 8, 12, and 24 h
      after surgery. Patients with a VAS score >3 were treated with ketorolac 30 mg as
      needed. Secondary outcomes included time to resumption of bowel function and
      length of hospital stay. Data in the two groups were compared using the two
      tailed Student's t test. All statistical tests were two-tailed at a significance
      level of 0.05. RESULTS: Demographic characteristics and clinical features of both
      groups were similar. Intensity of pain at rest in LG compared with PG was
      significantly lower during the first 24 h post-operatively. LG patients reported
      significantly less pain during movements at 2-, 12-, and 24-h post-surgery than
      PG patients. The study showed that ketorolac consumption was significantly higher
      in PG: mean ketorolac consumption in LG was 43.77 +/- 13.86 mg and in PG 51.67 +/
      13.16 mg (p = 0.047). Compared with placebo, lidocaine infusion produced a 32 %
      reduction in time to the first drink (Cohen's d = 3.85), 16 % reduction in time
      to the first full diet (Cohen's d = 3.35), and 18 % reduction in time to the
      first bowel movement (Cohen's d = 2.30). Patients who received lidocaine stayed
      in hospital 1.2 days less than patients who received placebo (p < 0.01, Cohen's d
      = 0.72). There were no significant differences in surgery-related complications
      between the two groups. CONCLUSIONS: Perioperative continuous IV lidocaine
      infusion has a beneficial effect as regards post-operative pain, restoration of
      bowel function, and length of hospital stay in patients who have undergone hand
      assisted laparoscopic colon surgery.

PMID- 24030783
TI  - Peroxide-enhanced endoanal ultrasound in preoperative assessment of complex
      fistula-in-ano.
AB  - BACKGROUND: In complex fistula-in-ano, preoperative imaging can help identify
      secondary tracts and abscesses that can be missed, leading to recurrence. We
      evaluated hydrogen peroxide-enhanced endoanal ultrasound (PEEUS) in the
      characterization of fistula compared with standard clinical and operative
      assessment. METHODS: Patients with complex fistula-in-ano treated between
      February 2008 and May 2009 at our institution were prospectively evaluated by
      PEEUS with recording of the preoperative clinical examination and intraoperative
      details of the fistula. Of the 135 patients with fistula-in-ano, 68 met the
      inclusion criteria for complex fistula-in-ano. Correlation of clinical findings
      and PEEUS to the gold standard intraoperative findings was assessed in
      characterizing the fistula. The percent agreement between the clinical and PEEUS
      findings against the gold standard was derived, and the kappa statistic for
      agreement was determined. RESULTS: The mean age of the cohort was 42.54 +/- 10.86
      years. The fistula tracts were curvilinear, high, and transsphincteric in 16
      (23.53%), 8 (11.76%), and 42 (61.76%) patients, respectively. Secondary tracts
      and associated abscess cavities were seen in 28 (33.82%) and 35 (51.47%)
      patients, respectively. PEEUS correlated better than clinical examination with
      regard to site (92.65 vs 79.41%; p < 0.001) and course (91.18 vs 77.94%; p <
      0.001) of secondary tract and associated abscesses (89.71 vs 80.88%; p = 0.02).
      There was a trend of better correlation of PEEUS compared to clinical examination
      in classifying the primary tract as per Park's system (88.24 vs 79.41%; p =
      0.06), but it did not reach statistical significance. PEEUS and clinical
      examination were comparable in correlation of the level of the primary tract
      (kappa: 0.86 vs 0.78; p = 0.22) and the site of internal opening (kappa: 0.97 vs
      0.89; p = 0.22). The operative decision was changed in 13 (19.12%) subjects based
      on PEEUS findings. CONCLUSIONS: PEEUS is a feasible and efficient tool in the
      routine preoperative assessment of complex fistula-in-ano.

PMID- 24030784
TI  - Defecatory disorders in anorexia nervosa: a clinical study.
AB  - BACKGROUND: Defecatory disorders in patients with eating disorders have been
      overlooked. We evaluated the prevalence and type of defecatory disorders in
      patients with anorexia nervosa. METHODS: The aim of our questionnaire-based study
      was to determine the prevalence of constipation and faecal incontinence (FI) in
      patients with anorexia nervosa attending our dedicated eating disorders
      outpatient clinics and whether length of illness and low body mass index (BMI)
      exacerbate both constipation and FI. The Wexner constipation score (WCS),
      Altomare's obstructed defecation score (OD score) and the faecal incontinence
      severity index (FISI) were used to evaluate constipation and incontinence. A WCS
      >=5, OD score >=10 and a FISI >=10 were considered clinically relevant. RESULTS:
      Eighty-five patients (83 females; mean age 28 years +/- 13) with anorexia nervosa
      (study group) and mean BMI of 16 +/- 2 kg/m(2) (range 14-19 kg/m(2)) were
      studied. This group was compared to 57 healthy volunteers (control group) with
      mean BMI of 22 +/- 3 kg/m(2) (range 20-27 kg/m(2)). In the study group, 79/85
      (93%) patients suffered from defecatory disorders defined as at least one
      abnormal score, either WCS, OD score or FISI, compared to 7/57 (12%) controls (p
      < 0.001). Constipation (defined as WCS >=5) was present in 70/85 (83%) patients
      with anorexia and in 7/57 (12%) controls (p = 0.001), while obstructed defecation
      syndrome (defined as OD score >=10) was present in 71/85 (84%) patients with
      anorexia and 7/57 (12%) controls (p < 0.001). In patients with anorexia, the mean
      WCS score was 10 +/- 5 standard deviation (SD) (3 +/- 2 SD in controls; p <
      0.001), and the mean OD score was 12 +/- 4 SD (3 +/- 4 SD in controls; p <
      0.001). Overall, 62/85 (73%) patients with anorexia had FI defined as FISI score
      >=10, and the mean FISI score in anorexia patients was 12 +/- 9 SD. A combination
      of constipation and FI (either both WCS and FISI abnormal or both OD score and
      FISI abnormal) was present in 55/85 (64%) and 8/85 (9%) presented with FI alone.
      Moreover, all results are influenced by the severity of the disease measured by
      BMI and duration. The percentage of defecatory disorders rises from 75 to 100%
      when BMI is <18 kg/m(2) and from 60 to 75% when the duration of illness is >=5
      years (p < 0.001 and p = 0.021, respectively). CONCLUSIONS: Defecatory disorders
      are associated with anorexia nervosa and increased with the duration and severity
      of the illness.

PMID- 24030785
TI  - Inhibition of otopathogenic biofilms by organoselenium-coated tympanostomy tubes.
AB  - IMPORTANCE: Tube occlusion and post-tympanostomy tube otorrhea (PTTO) are 2 major
      sequelae of tympanostomy tube placement. Plugging negates the function of the
      tympanostomy tubes and, along with chronic PTTO, can be financially burdensome
      owing to repeated surgical procedures and additional treatments. OBJECTIVE: To
      investigate the effectiveness of an organoselenium (OSe) coating on Donaldson
      tympanostomy tubes in inhibiting biofilm formation on the tympanostomy tubes.
      DESIGN: In vitro microbiologic study; all experiments were performed in a Texas
      Tech University Health Sciences Center basic sciences laboratory. INTERVENTIONS:
      Inhibition of biofilm formation was investigated by incubating OSe-coated vs
      uncoated (control) tympanostomy tubes in a nutrient broth containing either
      Staphylococcus aureus (Sa) expressing green fluorescent protein (GFP),
      nontypeable Haemophilus influenzae (NTHi) expressing GFP, or Moraxella
      catarrhalis (Mc) for 48 hours at 37  degrees C. All biofilms were quantified via
      colony-forming unit (CFU) assays. The Sa and NTHi biofilms were visualized using
      confocal laser-scanning microscopy (CLSM) and analyzed using the COMSTAT program.
      MAIN OUTCOMES AND MEASURES: The CFU assays, CLSM, and COMSTAT analysis revealed
      that compared with uncoated control tympanostomy tubes, OSe-coated tympanostomy
      tubes are able to inhibit Sa, NTHi, and Mc biofilm formation. RESULTS: The Sa and
      NTHi developed thick mature biofilms containing considerable biomass on uncoated
      tympanostomy tubes as determined by CLSM and COMSTAT analysis, while the OSe
      coating on the tympanostomy tubes drastically inhibited biofilm formation by Sa
      and NTHi. Quantitative CFU analysis revealed that this reduction in biofilm
      formation was significant, 6 logs for Sa (P < .001) and 4 logs for NTHi (P =
      .02). OSe coating also inhibited biofilm formation by Mc with a 4.5-log reduction
      (P < .001). CONCLUSIONS AND RELEVANCE: The OSe coating is a potential long
      lasting agent to prevent biofilm development on tympanostomy tubes by
      otopathogens.

PMID- 24030786
TI  - X-ray CT and histological imaging of xylem vessels organization in Mimosa pudica.
AB  - Mimosa pudica has three distinct specialized organs, namely, pulvinus, secondary
      pulvinus, and pulvinule, which are respectively controlling the movements of
      petioles, leaflets, and pinna in response to external stimuli. Water flow is a
      key factor for such movements, but detailed studies on the organization of the
      vascular system for water transport in these organs have not been published yet.
      In this study, organizations of the xylem vessels and morphological features of
      the pulvinus, the secondary pulvinus, and the pulvinule were experimentally
      investigated by X-ray computed tomography and histological technique. Results
      showed that the xylem vessels were circularly distributed in the specialized
      motile organs and reorganized into distinct vascular bundles at the extremities.
      The number and the total cross-sectional area of the xylem vessels were increased
      inside the specialized motile organs. Morphological characteristics obtained in
      this study provided new insight to understand the functions of the vascular
      networks in the dynamic movements of M. pudica.

PMID- 24030787
TI  - Modified lambda-shaped lymphaticovenular anastomosis with supermicrosurgical
      lymphoplasty technique for a cancer-related lymphedema patient.
AB  - Supermicrosurgical lymphaticovenular anastomosis (LVA) has become a useful option
      for the treatment of compression-refractory lymphedema with its effectiveness and
      less invasiveness. It is important to make as many bypasses as possible for
      better treatment results of LVA operation. We report a secondary lymphedema case
      successfully treated using a modified lambda-shaped LVA. A 62-year-old female
      with secondary lower extremity lymphedema (LEL) refractory to conservative
      treatments underwent LVA operation. A modified lambda-shaped LVA was performed at
      the left groin. In modified lambda-shaped LVA, two lymphatic vessels were
      transected, and both ends of the proximal and distal sides were converged
      respectively for an end-to-side and end-to-end anastomoses to one vein. Using
      modified lambda-shaped LVA, four lymph flows of two lymphatic vessels could be
      bypassed into a vein. Six months after the LVA surgery, her left LEL index
      decreased from 261 to 247, indicating edematous volume reduction. Modified lambda
      shaped LVA effectively bypasses all lymph flows from two lymphatic vessels, when
      only one large vein can be found in the surgical field.

PMID- 24030788
TI  - Cost-effectiveness of rivaroxaban versus warfarin for stroke prevention in atrial
      fibrillation in the Belgian healthcare setting.
AB  - BACKGROUND: Warfarin, an inexpensive drug that has been available for over half a
      century, has been the mainstay of anticoagulant therapy for stroke prevention in
      patients with atrial fibrillation (AF). Recently, rivaroxaban, a novel oral
      anticoagulant (NOAC) which offers some distinct advantages over warfarin, the
      standard of care in a world without NOACs, has been introduced and is now
      recommended by international guidelines. OBJECTIVE: The aim of this study was to
      evaluate, from a Belgian healthcare payer perspective, the cost-effectiveness of
      rivaroxaban versus use of warfarin for the treatment of patients with non
      valvular AF at moderate to high risk. METHODS: A Markov model was designed and
      populated with local cost estimates, safety-on-treatment clinical results from
      the pivotal phase III ROCKET AF trial and utility values obtained from the
      literature. RESULTS: Rivaroxaban treatment was associated with fewer ischemic
      strokes and systemic embolisms (0.308 vs. 0.321 events), intracranial bleeds
      (0.048 vs. 0.063), and myocardial infarctions (0.082 vs. 0.095) per patient
      compared with warfarin. Over a lifetime time horizon, rivaroxaban led to a
      reduction of 0.042 life-threatening events per patient, and increases of 0.111
      life-years and 0.094 quality-adjusted life-years (QALYs) versus warfarin
      treatment. This resulted in an incremental cost-effectiveness ratio of ?8,809 per
      QALY or ?7,493 per life-year gained. These results are based on valuated data
      from 2010. Sensitivity analysis indicated that these results were robust and that
      rivaroxaban is cost-effective compared with warfarin in 87 % of cases should a
      willingness-to-pay threshold of ?35,000/QALY gained be considered. CONCLUSIONS:
      The present analysis suggests that rivaroxaban is a cost-effective alternative to
      warfarin therapy for the prevention of stroke in patients with AF in the Belgian
      healthcare setting.

PMID- 24030790
TI  - Immunisation coverage in India remains too low, study finds.

PMID- 24030789
TI  - Clinical and neurophysiological profile of four German families with
      spinocerebellar ataxia type 14.
AB  - Spinocerebellar ataxia type 14 (SCA14) is an autosomal-dominant ataxia caused by
      point mutations of the Protein Kinase C Gamma gene. In addition to slowly
      progressive cerebellar ataxia, it is characterised by dystonia and myoclonus.
      With scant neuropathological data and no detailed neurophysiological examinations
      little is known on extracerebellar consequences of SCA14 related cerebellar
      pathology. To this end, we here delineate clinical phenomenology and
      neurophysiology of four German SCA14 families. Detailed clinical examination
      including ataxia severity evaluation by means of the Scale for the Assessment and
      Rating of Ataxia (SARA) was carried out in 9 affected family members (mean age
      49.8 years +/- 14.4 SD). Motor thresholds (MT), the contralateral silent period
      (CSP), short interval intracortical inhibition (SICI) and intracortical
      facilitation (ICF), interhemispheric inhibition (IHI) and short afferent
      inhibition (SAI) were determined using transcranial magnetic stimulation (TMS).
      Somatosensory evoked potentials (SEP) of the median nerve, and acoustic and
      visual evoked potentials (AEP, VEP) were also performed. Most patients reported
      symptoms since early childhood. There was a positive correlation between age and
      SARA scores (r = .721, P < 0.05). Patients had cerebellar ataxia, mild dystonia
      (focal, task-specific or segmental), subtle pyramidal signs and myoclonus. SICI
      increased with increasing conditioning pulse intensities in healthy controls but
      not in patients. Other neurophysiological parameters did not differ between
      groups. SCA14 is a slowly progressive ataxia associated with mild dystonia and
      myoclonus. Reduced SICI reflects abnormalities of intracortical inhibitory
      circuits. 

PMID- 24030791
TI  - FDA to tighten labeling on long acting opioids.

PMID- 24030806
TI  - Abstracts of the 7th Joint Meeting of the British Division of the International
      Academy of Pathology and the Pathological Society of Great Britain & Ireland.
      June 18-21, 2013. Edinburgh, United Kingdom.

PMID- 24030807
TI  - Effects of high-amount-high-intensity exercise on in vivo platelet activation:
      modulation by lipid peroxidation and AGE/RAGE axis.
AB  - Physical activity is associated with cardiovascular risk reduction, but the
      effects of exercise on platelet activation remain controversial. We investigated
      the effects of regular high-amount, high intensity aerobic exercise on in vivo
      thromboxane (TX)-dependent platelet activation and plasma levels of platelet
      derived proteins, CD40L and P-selectin, and whether platelet variables changes
      may be related to changes in high-density lipoprotein (HDL) and in the extent of
      oxidative stress and oxidative stress-related inflammation, as reflected by
      urinary isoprostane excretion and endogenous soluble receptor for advanced
      glycation end-products (esRAGE), respectively. Urinary excretion of 11-dehydro
      TXB2 and 8-iso-prostaglandin (PG)F(2alpha) and plasma levels of P-selectin, CD40L
      and esRAGE were measured before and after a eight-week standardised aerobic high
      amount-high-intensity training program in 22 sedentary subjects with low-to
      intermediate risk. Exercise training had a clear beneficial effect on HDL
      cholesterol (+10%, p=0.027) and triglyceride (-27%, p=0.008) concentration. In
      addition, a significant (p<0.0001) decrease in urinary 11-dehydro-TXB2 (26%), 8
      iso-PGF(2alpha) (21%), plasma P-selectin (27%), CD40L (35%) and a 61% increase in
      esRAGE were observed. Multiple regression analysis revealed that urinary 8-iso
      PGF(2alpha) [beta=0.33, SEM=0.116, p=0.027] and esRAGE (beta=-0.30, SEM=31.3,
      p=0.046) were the only significant predictors of urinary 11-dehydro-TXB2
      excretion rate over the training period. In conclusion, regular high-amount-high
      intensity exercise training has broad beneficial effects on platelet activation
      markers, paralleled and possibly associated with changes in the lipoprotein
      profile and in markers of lipid peroxidation and AGE/RAGE axis. Our findings may
      help explaining why a similar amount of exercise exerts significant benefits in
      preventing cardiovascular events.

PMID- 24030808
TI  - Hemoglobin levels and red blood cell indices in mid-gestational fetuses with beta
      thalassemia/HbE, beta-thalassemia trait or Hb E trait and normal fetuses.
AB  - OBJECTIVE: To compare red blood cell indices among normal, beta-thalassemia trait
      or hemoglobin (Hb) E trait, and beta-thalassemia/Hb E diseases mid-gestational
      fetuses. METHODS: One hundred seventy-five fetuses at risk of beta-thalassemia/Hb
      E disease undergoing cordocentesis with determination of Hb levels and red blood
      cell indices at mid-pregnancy were recruited. The fetal diagnoses were based on
      fetal Hb typing and DNA analysis. The fetuses were divided into three groups:
      normal, beta-thalassemia trait or Hb E trait, and beta-thalassemia/Hb E disease.
      RESULTS: The prevalence of beta-thalassemia/Hb E disease, beta-thalassemia trait
      or Hb E trait, and normal fetuses was 32.6% (57 cases), 28.6% (50 cases) and
      36.6% (64 cases), respectively. Mean Hb levels and red blood cell indices were
      not significantly different among the three groups of fetuses. However, almost
      10% of beta-thalassemia/Hb E fetuses had some degree of anemia. The most anemic
      fetuses had a beta(0) mutation. CONCLUSION: There is no significant difference in
      Hb level and red blood cell indices among fetuses at risk of beta-thalassemia/Hb
      E disease.

PMID- 24030809
TI  - Subtypes of type I IFN differentially enhance cytokine expression by suboptimally
      stimulated CD4(+) T cells.
AB  - Human type I interferons (IFNs) include IFN-beta and 12 subtypes of IFN-alpha.
      During viral infection, infiltrating memory CD4(+) T cells are exposed to IFNs,
      but their impact on memory T-cell function is poorly understood. To address this,
      we pretreated PBMCs with different IFNs for 16 h before stimulation with
      Staphylococcus aureus enterotoxin B and measured cytokine expression by flow
      cytometry. IFN-alpha8 and -alpha10 most potently enhanced expression of IFN
      gamma, IL-2, and IL-4. Potency among the subtypes differed most at doses between
      10 and 100 U/mL. While enhancement of IL-2 and IL-4 correlated with the time of
      preincubation with type I IFN, IFN-gamma production was enhanced best when IFN
      alpha was added immediately preceding or simultaneously with T-cell stimulation.
      Comparison of T-cell responses to multiple doses of Staphylococcus aureus
      enterotoxin B and to peptide libraries from RSV or CMV demonstrated that IFN
      alpha best enhanced cytokine expression when CD4(+) T cells were suboptimally
      stimulated. We conclude that type I IFNs enhance Th1 and Th2 function with dose
      dependency and subtype specificity, and best when T-cell stimulation is
      suboptimal. While type I IFNs may beneficially enhance CD4(+) T-cell memory
      responses to vaccines or viral pathogens, they may also enhance the function of
      resident Th2 cells and exacerbate allergic inflammation. 

PMID- 24030810
TI  - Religion and health-promoting behaviors among emerging adults.
AB  - Studies suggest we capitalize upon religion's health benefits to prevent obesity.
      The purpose of this qualitative descriptive study was to determine how emerging
      adults used religion to manage their health. Two focus groups were conducted
      among White and African American participants. Content analysis of the data
      revealed categories about their attitudes regarding parental and religious
      influences, religion's influence on behavior, negative health effects of
      religion, barriers, obesity prevention, and health promotion programs. Society
      sends out "easy" solutions for unhealthy behaviors, but we should focus on
      healthy behavior benefits, remove barriers, and consider religion's part in
      health promotion (obesity prevention). 

PMID- 24030811
TI  - Effects of ionic radius of redox-inactive bio-related metal ions on the radical
      scavenging activity of flavonoids evaluated using photometric titration.
AB  - Mg(2+) enhanced the scavenging activity of (+)-catechin and quercetin against the
      2,2-diphenyl-1-picrylhydrazyl radical (DPPH), while Al(3+) decreased their
      activity. Such effects of Mg(2+) and Al(3+) were not observed for kaempferol.
      Na(+) and Ca(2+) with large ionic radii showed little effect on the DPPH
      scavenging activity of these three flavonoids. 

PMID- 24030812
TI  - Trigonal prismatic Cu(I) and Ag(I) pyrazolato nanocage hosts: encapsulation of S8
      and hydrocarbon guests.
AB  - Two neutral hexanuclear trigonal prismatic cage molecules have been synthesized
      by coupling two planar triangular M3pz3-panels, M = Cu(I) and Ag(I), in eclipsed
      geometry. The ~230 A(3) cage volume can be either vacant or occupied by neutral
      guests. The crystal structures of the M6-cyclohexane and Ag6-S8 host-guest
      species have been determined.

PMID- 24030813
TI  - Adenocarcinoma arising from tubulovillous adenoma in a native bladder following
      gastrocystoplasty.
AB  - Gastrocystoplasty is a surgical form of bladder augmentation which improves
      bladder capacity and compliance. Patients who undergo bladder augmentation with a
      gastric remnant are at increased risk for malignancy. The most common types of
      tumors in this situation were adenocarcinoma and urothelial carcinoma. Most of
      the adenocarcinomas arise in the gastric remnant or anastomotic site, and
      adenocarcinomas arising in the residual native bladder are extremely rare. We
      report on a patient who received gastrocystoplasty 16 years ago. She suffered
      from recurrent urinary tract infections for a year and cystoscopy showed a tumor
      in the bladder trigone. Pathologic examination showed tubulovillous adenoma with
      malignant transformation to adenocarcinoma. The tumor consisted of intact
      adenomatous architecture from low-grade dysplastic gland to adenocarcinoma, which
      suggested that the pathogenesis might be related to intestinal metaplasia and
      dysplasia. The unique location and immunohistologic findings of the tumor
      suggested that it originated in the bladder mucosa.

PMID- 24030817
TI  - Substrate hydrolysis triggered formation of fluorescent gold nanoclusters--a new
      platform for the sensing of enzyme activity.
AB  - Substrate hydrolysis was utilized to trigger a "top-down" etching process for the
      generation of fluorescent gold nanoclusters, and the changes in emission
      intensity of the assay solution provide a facile way for the sensing of enzyme
      activity. 

PMID- 24030815
TI  - Role of the ubiquitin-proteasome system in the regulation of P2Y13 receptor
      expression: impact on hepatic HDL uptake.
AB  - The protective effect of high density lipoproteins (HDL) against atherosclerosis
      is mainly attributed to their capacity to transport excess cholesterol from
      peripheral tissues back to the liver for further elimination into the bile, a
      process called reverse cholesterol transport (RCT). Recently, the importance of
      the P2Y13 receptor (P2Y13-R) was highlighted in HDL metabolism since HDL uptake
      by the liver was decreased in P2Y13-R deficient mice, which translated into
      impaired RCT. Here, we investigated for the first time the molecular mechanisms
      regulating cell surface expression of P2Y13-R. When transiently expressed, P2Y13
      R was mainly detected in the endoplasmic reticulum (ER) and strongly subjected to
      proteasome degradation while its homologous P2Y12 receptor (P2Y12-R) was
      efficiently targeted to the plasma membrane. We observed an inverse correlation
      between cell surface expression and ubiquitination level of P2Y13-R in the ER,
      suggesting a close link between ubiquitination of P2Y13-R and its efficient
      targeting to the plasma membrane. The C-terminus tail exchange between P2Y13-R
      and P2Y12-R strongly restored plasma membrane expression of P2Y13-R, suggesting
      the involvement of the intra-cytoplasmic tail of P2Y13-R in expression defect.
      Accordingly, proteasomal inhibition increased plasma membrane expression of
      functionally active P2Y13-R in hepatocytes, and consequently stimulated P2Y13-R
      mediated HDL endocytosis. Importantly, proteasomal inhibition strongly
      potentiated HDL hepatic uptake (>200 %) in wild-type but not in P2Y13-R-deficient
      mice, thus reinforcing the role of P2Y13-R expression in regulating HDL
      metabolism. Therefore, specific inhibition of the ubiquitin-proteasome system
      might be a novel powerful HDL therapy to enhance P2Y13-R expression and
      consequently promote the overall RCT. 

PMID- 24030818
TI  - Predicting perception in noise using cortical auditory evoked potentials.
AB  - Speech perception in background noise is a common challenge across individuals
      and health conditions (e.g., hearing impairment, aging, etc.). Both behavioral
      and physiological measures have been used to understand the important factors
      that contribute to perception-in-noise abilities. The addition of a physiological
      measure provides additional information about signal-in-noise encoding in the
      auditory system and may be useful in clarifying some of the variability in
      perception-in-noise abilities across individuals. Fifteen young normal-hearing
      individuals were tested using both electrophysiology and behavioral methods as a
      means to determine (1) the effects of signal-to-noise ratio (SNR) and signal
      level and (2) how well cortical auditory evoked potentials (CAEPs) can predict
      perception in noise. Three correlation/regression approaches were used to
      determine how well CAEPs predicted behavior. Main effects of SNR were found for
      both electrophysiology and speech perception measures, while signal level effects
      were found generally only for speech testing. These results demonstrate that when
      signals are presented in noise, sensitivity to SNR cues obscures any encoding of
      signal level cues. Electrophysiology and behavioral measures were strongly
      correlated. The best physiological predictors (e.g., latency, amplitude, and area
      of CAEP waves) of behavior (SNR at which 50 % of the sentence is understood) were
      N1 latency and N1 amplitude measures. In addition, behavior was best predicted by
      the 70-dB signal/5-dB SNR CAEP condition. It will be important in future studies
      to determine the relationship of electrophysiology and behavior in populations
      who experience difficulty understanding speech in noise such as those with
      hearing impairment or age-related deficits. 

PMID- 24030819
TI  - Ag-promoted azido-carbocyclization of activated alkenes via C-H bond cleavage.

PMID- 24030820
TI  - Paradoxical growth of presumed optochiasmatic tuberculomas following medical
      therapy.
AB  - IMPORTANCE: Tuberculosis is an endemic infectious disease in developing
      countries. Patients receiving treatment for systemic tuberculosis may develop
      paradoxical growth of tuberculomas in the brain, which can lead to vision loss.
      OBSERVATIONS: We describe 3 patients who had paradoxical development of
      tuberculomas in the anterior optic pathway during treatment for tuberculosis and
      presented with acute vision loss. These optochiasmatic tuberculomas were not
      present at the initial presentation of tuberculosis and appeared on brain
      magnetic resonance imaging at the time of presentation with vision loss. Vision
      improved on instituting systemic corticosteroids in addition to antituberculous
      treatment. CONCLUSIONS AND RELEVANCE: As there was visual recovery after patients
      began receiving systemic corticosteroids and there was no worsening of the
      systemic condition, it is reasonable to assume that the optochiasmatic
      tuberculomas resulted from a paradoxical reaction. It is important to recognize
      this condition and initiate prompt treatment to reduce visual morbidity.

PMID- 24030821
TI  - Allosteric lariat peptide inhibitors of Abl kinase.
AB  - Going against tradition: although most kinase inhibitors are ATP competitive,
      lariat peptides inhibit Abl kinase activity in an ATP-uncompetitive manner.
      Further, lariat peptides discriminated Src family kinases, and recognize the
      allosteric region that lies adjacent to the ATP binding pocket in the Abl kinase
      catalytic cleft.

PMID- 24030822
TI  - Mutagenic analysis of the intracellular portals of the human 5-HT3A receptor.
AB  - Structural models of Cys-loop receptors based on homology with the Torpedo
      marmorata nicotinic acetylcholine receptor infer the existence of cytoplasmic
      portals within the conduction pathway framed by helical amphipathic regions
      (termed membrane-associated (MA) helices) of adjacent intracellular M3-M4 loops.
      Consistent with these models, two arginine residues (Arg(436) and Arg(440))
      within the MA helix of 5-hydroxytryptamine type 3A (5-HT3A) receptors act
      singularly as rate-limiting determinants of single-channel conductance (gamma).
      However, there is little conservation in primary amino acid sequences across the
      cytoplasmic loops of Cys-loop receptors, limiting confidence in the fidelity of
      this particular aspect of the 5-HT3A receptor model. We probed the majority of
      residues within the MA helix of the human 5-HT3A subunit using alanine- and
      arginine-scanning mutagenesis and the substituted cysteine accessibility method
      to determine their relative influences upon gamma. Numerous residues, prominently
      those at the 435, 436, 439, and 440 positions, were found to markedly influence
      gamma. This approach yielded a functional map of the 5-HT3A receptor portals,
      which agrees well with the homology model. 

PMID- 24030823
TI  - Fatty acid labeling from glutamine in hypoxia can be explained by isotope
      exchange without net reductive isocitrate dehydrogenase (IDH) flux.
AB  - Acetyl-CoA is an important anabolic precursor for lipid biosynthesis. In the
      conventional view of mammalian metabolism, acetyl-CoA is primarily derived by the
      oxidation of glucose-derived pyruvate in mitochondria. Recent studies have
      employed isotope tracers to show that in cancer cells grown in hypoxia or with
      defective mitochondria, a major fraction of acetyl-CoA is produced via another
      route, reductive carboxylation of glutamine-derived alpha-ketoglutarate
      (catalyzed by reverse flux through isocitrate dehydrogenase, IDH). Here, we
      employ a quantitative flux model to show that in hypoxia and in cells with
      defective mitochondria, oxidative IDH flux persists and may exceed the reductive
      flux. Therefore, IDH flux may not be a net contributor to acetyl-CoA production,
      although we cannot rule out net reductive IDH flux in some compartments. Instead
      of producing large amounts of net acetyl-CoA reductively, the cells adapt by
      reducing their demand for acetyl-CoA by importing rather than synthesizing fatty
      acids. Thus, fatty acid labeling from glutamine in hypoxia can be explained by
      spreading of label without net reductive IDH flux. 

PMID- 24030824
TI  - Aspartic acid 397 in subunit B of the Na+-pumping NADH:quinone oxidoreductase
      from Vibrio cholerae forms part of a sodium-binding site, is involved in cation
      selectivity, and affects cation-binding site cooperativity.
AB  - The Na(+)-pumping NADH:quinone complex is found in Vibrio cholerae and other
      marine and pathogenic bacteria. NADH:ubiquinone oxidoreductase oxidizes NADH and
      reduces ubiquinone, using the free energy released by this reaction to pump
      sodium ions across the cell membrane. In a previous report, a conserved aspartic
      acid residue in the NqrB subunit at position 397, located in the cytosolic face
      of this protein, was proposed to be involved in the capture of sodium. Here, we
      studied the role of this residue through the characterization of mutant enzymes
      in which this aspartic acid was substituted by other residues that change charge
      and size, such as arginine, serine, lysine, glutamic acid, and cysteine. Our
      results indicate that NqrB-Asp-397 forms part of one of the at least two sodium
      binding sites and that both size and charge at this position are critical for the
      function of the enzyme. Moreover, we demonstrate that this residue is involved in
      cation selectivity, has a critical role in the communication between sodium
      binding sites, by promoting cooperativity, and controls the electron transfer
      step involved in sodium uptake (2Fe-2S -> FMNC). 

PMID- 24030825
TI  - Target specificity of the E3 ligase LUBAC for ubiquitin and NEMO relies on
      different minimal requirements.
AB  - The ubiquitination of NEMO with linear ubiquitin chains by the E3-ligase LUBAC is
      important for the activation of the canonical NF-kappaB pathway. NEMO
      ubiquitination requires a dual target specificity of LUBAC, priming on a lysine
      on NEMO and chain elongation on the N terminus of the priming ubiquitin. Here we
      explore the minimal requirements for these specificities. Effective linear chain
      formation requires a precise positioning of the ubiquitin N-terminal amine in a
      negatively charged environment on the top of ubiquitin. Whereas the RBR-LDD
      region on HOIP is sufficient for targeting the ubiquitin N terminus, the priming
      lysine modification on NEMO requires catalysis by the RBR domain of HOIL-1L as
      well as the catalytic machinery of the RBR-LDD domains of HOIP. Consequently,
      target specificity toward NEMO is determined by multiple LUBAC components,
      whereas linear ubiquitin chain elongation is realized by a specific interplay
      between HOIP and ubiquitin. 

PMID- 24030826
TI  - The functional interaction of mitochondrial Hsp70s with the escort protein Zim17
      is critical for Fe/S biogenesis and substrate interaction at the inner membrane
      preprotein translocase.
AB  - The yeast protein Zim17 belongs to a unique class of co-chaperones that maintain
      the solubility of Hsp70 proteins in mitochondria and plastids of eukaryotic
      cells. However, little is known about the functional cooperation between Zim17
      and mitochondrial Hsp70 proteins in vivo. To analyze the effects of a loss of
      Zim17 function in the authentic environment, we introduced novel conditional
      mutations within the ZIM17 gene of the model organism Saccharomyces cerevisiae
      that allowed a recovery of temperature-sensitive but respiratory competent zim17
      mutant cells. On fermentable growth medium, the mutant cells were prone to
      acquire respiratory deficits and showed a strong aggregation of the mitochondrial
      Hsp70 Ssq1 together with a concomitant defect in Fe/S protein biogenesis. In
      contrast, under respiring conditions, the mitochondrial Hsp70s Ssc1 and Ssq1
      exhibited only a partial aggregation. We show that the induction of the zim17
      mutant phenotype leads to strong import defects for Ssc1-dependent matrix
      targeted precursor proteins that correlate with a significantly reduced binding
      of newly imported substrate proteins to Ssc1. We conclude that Zim17 is not only
      required for the maintenance of mtHsp70 solubility but also directly assists the
      functional interaction of mtHsp70 with substrate proteins in a J-type co
      chaperone-dependent manner. 

PMID- 24030827
TI  - The role of nonconserved residues of Archaeoglobus fulgidus ferritin on its
      unique structure and biophysical properties.
AB  - Archaeoglobus fulgidus ferritin (AfFtn) is the only tetracosameric ferritin known
      to form a tetrahedral cage, a structure that remains unique in structural
      biology. As a result of the tetrahedral (2-3) symmetry, four openings (~45 A in
      diameter) are formed in the cage. This open tetrahedral assembly contradicts the
      paradigm of a typical ferritin cage: a closed assembly having octahedral (4-3-2)
      symmetry. To investigate the molecular mechanism affecting this atypical
      assembly, amino acid residues Lys-150 and Arg-151 were replaced by alanine. The
      data presented here shed light on the role that these residues play in shaping
      the unique structural features and biophysical properties of the AfFtn. The x-ray
      crystal structure of the K150A/R151A mutant, solved at 2.1 A resolution,
      indicates that replacement of these key residues flips a "symmetry switch." The
      engineered molecule no longer assembles with tetrahedral symmetry but forms a
      typical closed octahedral ferritin cage. Small angle x-ray scattering reveals
      that the overall shape and size of AfFtn and AfFtn-AA in solution are consistent
      with those observed in their respective crystal structures. Iron binding and
      release kinetics of the AfFtn and AfFtn-AA were investigated to assess the
      contribution of cage openings to the kinetics of iron oxidation, mineralization,
      or reductive iron release. Identical iron binding kinetics for AfFtn and AfFtn-AA
      suggest that Fe(2+) ions do not utilize the triangular pores for access to the
      catalytic site. In contrast, relatively slow reductive iron release was observed
      for the closed AfFtn-AA, demonstrating involvement of the large pores in the
      pathway for iron release. 

PMID- 24030828
TI  - The Ccr4-not protein complex regulates the phase of the Neurospora circadian
      clock by controlling white collar protein stability and activity.
AB  - In the Neurospora circadian negative feedback loop, white collar 1 (WC-1) and WC
      2 form the WC complex that activates frequency (frq) transcription. Here we show
      that Not1 is a WC-interacting protein and is important for maintaining WC levels.
      The not1 transcript displays a circadian oscillation with a similar phase as frq.
      Down-regulation of not1 leads to low levels of WC-1 and WC-2 and a delayed
      circadian phase as a result of increased protein degradation and increased WC
      activity. Protein purification of Not1 shows that it is part of the Neurospora
      Ccr4-Not complex. ccr4 is a clock-controlled gene and is regulated directly by
      the WC complex. Down-regulation of ccr4 results in a phase delay and period
      lengthening of the clock. Together, our findings suggest that the Ccr4-Not
      complex participates in the Neurospora clock function by interacting with and
      regulating the WC complex.

PMID- 24030829
TI  - Transthyretin proteins regulate angiogenesis by conferring different molecular
      identities to endothelial cells.
AB  - Familial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and
      the most common form of hereditary amyloidosis is caused by an amyloidogenic
      variant of transthyretin (TTR) with a substitution of methionine for valine at
      position 30 (V30M). Until now, the available efficient therapy is liver
      transplantation, when performed in an early phase of the onset of the disease
      symptoms. However, transplanted FAP patients have a significantly higher
      incidence of early hepatic artery thrombosis compared with non-FAP transplanted
      patients. Because FAP was described as an independent risk factor for early
      hepatic artery thrombosis, more studies to understand the underlying mechanisms
      involved in this outcome are of the utmost importance. Knowing that the liver is
      the major site for TTR production, we investigated the biological effects of TTR
      proteins in the vasculature and on angiogenesis. In this study, we identified
      genes differentially expressed in endothelial cells exposed to the WT or V30M
      tetramer. We found that endothelial cells may acquire different molecular
      identities when exposed to these proteins, and consequently TTR could regulate
      angiogenesis. Moreover, we show that V30M decreases endothelial survival by
      inducing apoptosis, and it inhibits migration. These findings provide new
      knowledge that may have critical implications in the prevention of early hepatic
      artery thrombosis in FAP patients after liver transplantation. 

PMID- 24030830
TI  - Transcription factor NF-Y is a functional regulator of the transcription of core
      clock gene Bmal1.
AB  - The circadian clock enables organisms to adjust to daily environmental changes
      and synchronize multiple molecular, biochemical, physiological, and behavioral
      processes accordingly. In mammalian clock work, Bmal1 is the most important core
      clock gene, which works with another core clock gene Clock to drive the
      expression of other clock genes and clock-controlled genes. However, the
      regulation of Bmal1 has not been fully understood. This work was aimed at
      identifying the positive regulator(s) of Bmal1 transcription. A series of 5'
      deletion reporter constructs was generated, and binding site mutations of mouse
      Bmal1 promoter fragments were cloned into pGL3-basic and pGL3(R2.1)-basic
      plasmids and transfected into NIH 3T3 cells. Luciferase activity was either
      measured 48 h after transfection or recorded for 4 days after serum shock. DNA
      affinity precipitation assay was used to detect the transcription factors binding
      to Bmal1 promoter. Small interfering RNA against nuclear factor Y, subunit A (NF
      YA) and dominant negative NF-YA were employed to study the role of NF-Y in Bmal1
      transcription regulation. Deletion and mutation analyses identified two clusters
      of CCAAT/GC-boxes at the proximal region of Bmal1 promoter as the activating cis
      elements. Bmal1 promoter activity was up-regulated by NF-Y and/or Sp1 and
      repressed by dominant negative NF-YA or siRNA against NF-YA. The activation of
      Bmal1 promoter activity by NF-Y and Sp1 was inhibited by Rev-Erbalpha. DNA
      affinity precipitation assay showed that NF-Y and Sp1 bound to the two CCAAT/GC
      clusters of Bmal1 promoter. These results indicate that NF-Y is a functional
      activator of Bmal1 transcription and it cooperates with Sp1 and Rev-Erbalpha to
      generate the daily cycle of Bmal1 expression. 

PMID- 24030832
TI  - Transforming growth factor-beta and the progression of renal disease.
AB  - Transforming growth factor-beta (TGF-beta) is a profibrotic cytokine found in
      chronic renal diseases, which initiates and modulates a variety of
      pathophysiological processes. It is synthesized by many renal cell types and
      exerts its biological functions through a variety of signalling pathways,
      including the Smad and MAPK pathways. In renal diseases, TGF-beta is upregulated
      and induces renal cells to produce extracellular matrix proteins leading to
      glomerulosclerosis as well as tubulointerstitial fibrosis. Different types of
      renal cells undergo different pathophysiological changes induced by TGF-beta,
      leading to apoptosis, hypertrophy and abnormalities of podocyte foot processes,
      which ultimately result in renal dysfunction. In this review, we describe the
      effects of TGF-beta on different renal cell types and the means by which TGF-beta
      participates in the pathomechanisms of glomerular and tubulointerstitial
      diseases. 

PMID- 24030831
TI  - Replacing the factor VIII C1 domain with a second C2 domain reduces factor VIII
      stability and affinity for factor IXa.
AB  - Factor VIII (FVIII) consists of a heavy chain (A1(a1)A2(a2)B domains) and light
      chain ((a3)A3C1C2 domains). To gain insights into a role of the FVIII C domains,
      we eliminated the C1 domain by replacing it with the homologous C2 domain. FVIII
      stability of the mutant (FVIIIC2C2) as measured by thermal decay at 55  degrees C
      of FVIII activity was markedly reduced (~11-fold), whereas the decay rate of
      FVIIIa due to A2 subunit dissociation was similar to WT FVIIIa. The binding
      affinity of FVIIIC2C2 for phospholipid membranes as measured by fluorescence
      resonance energy transfer was modestly lower (~2.8-fold) than that for WT FVIII.
      Among several anti-FVIII antibodies tested (anti-C1 (GMA8011), anti-C2 (ESH4 and
      ESH8), and anti-A3 (2D2) antibody), only ESH4 inhibited membrane binding of both
      WT FVIII and FVIIIC2C2. FVIIIa cofactor activity measured in the presence of each
      of the above antibodies was examined by FXa generation assays. The activity of WT
      FVIIIa was inhibited by both GMA8011 and ESH4, whereas the activity of FVIIIC2C2
      was inhibited by both the anti-C2 antibodies, ESH4 and ESH8. Interestingly,
      factor IXa (FIXa) binding affinity for WT FVIIIa was significantly reduced in the
      presence of GMA8011 (~10-fold), whereas the anti-C2 antibodies reduced FIXa
      binding affinity of FVIIIC2C2 variant (~4-fold). Together, the reduced stability
      plus impaired FIXa interaction of FVIIIC2C2 suggest that the C1 domain resides in
      close proximity to FIXa in the FXase complex and contributes a critical role to
      FVIII structure and function.

PMID- 24030833
TI  - Modality of chronic renal replacement therapy and survival--a complete cohort
      from Finland, 2000-2009.
AB  - BACKGROUND: Studies on dialysis modality and survival have shown conflicting
      results, mostly due to insufficient and varying control of confounding factors.
      Using comprehensive data on a well-defined patient cohort, we therefore
      investigated the association of dialysis modality with survival on chronic renal
      replacement therapy (RRT) and whether this association varies between subgroups
      of patients. METHODS: Survival analyses included all adult patients entering
      chronic RRT in Finland between 2000 and 2009 and used information obtained from
      the Finnish Registry for Kidney Diseases and the Finnish Kidney Transplant
      Registry. In our primary intention-to-treat (ITT) analysis, we calculated
      relative risk of death according to dialysis modality on Day 91 from RRT start,
      comparing peritoneal dialysis (PD) to haemodialysis (HD). Relative risks were
      adjusted for putative confounders. Interactions between treatment groups and
      other variables were estimated. RESULTS: Of the total 4463 patients, 42% died
      during the 10 years of follow-up. Median survival time was 5.2 years. In
      unadjusted ITT analysis, relative risk of death of PD patients was 0.65 (95% CI
      0.58-0.73, P < 0.001) compared with HD patients. With adjustment for 26
      variables, the corresponding relative risk of death was 1.07 (95% CI 0.94-1.22, P
      = 0.33). When censoring at time of kidney transplantation, the result was similar
      with a relative risk of death of 1.09 (95% CI 0.95-1.25, P = 0.24) on PD compared
      with HD. CONCLUSIONS: PD is associated with several factors generally related to
      good prognosis. After comprehensive adjustment for putative confounding factors
      with the ITT analysis approach, we found no significant difference in survival
      between PD and HD patients.

PMID- 24030834
TI  - Cerebral oxidative stress induces spatial working memory dysfunction in uremic
      mice: neuroprotective effect of tempol.
AB  - BACKGROUND: Chronic kidney disease (CKD) is frequently associated with uremic
      encephalopathy and cognitive impairment. Recent studies have demonstrated that
      cerebral oxidative stress contributes to cognitive dysfunction. Although
      oxidative stress has been reported to increase in the uremic rat brain, the
      relationship between increased oxidative stress and cognitive impairment in
      uremia is unclear. In the present study, the effects of tempol (TMP), an
      antioxidant drug, were investigated in uremic mice. METHODS: CKD was induced in
      male C57BL/6 mice (n = 8) by left nephrectomy and 2/3 electrocoagulation of the
      right renal cortex. Working memory performance was tested by the radial arm water
      maze test. We have prepared two protocols ('time course study' and 'treatment
      study'). First, we examined the working memory test and histological examination
      of mouse brains after 4 and 8 weeks. Next, we investigated the effect of TMP (3
      mM) against uremia-induced neurodegeneration and oxidative stress in the mouse
      brain. RESULTS: Eight weeks after CKD induction, vehicle-treated mice made
      significantly more errors than sham-operated control mice, while TMP improved
      working memory performance in CKD mice. CKD was associated with accumulation of 8
      hydroxy-2'-deoxyguanosine in the hippocampal neuronal cells, but not in TMP
      treated CKD mice. Increased numbers of pyknotic neuronal cells were observed in
      the hippocampus of CKD mice at 8 weeks, but pyknotic neuronal cell numbers were
      decreased under the influence of TMP in uremic mice. CONCLUSIONS: The present
      study provided evidence that uremia is associated with spatial working memory
      dysfunction in mice and that treatment with TMP protects against cerebral
      oxidative stress and improves cognitive dysfunction in uremic mice, suggesting
      their potential usefulness for the treatment of cognitive dysfunction in uremia.

PMID- 24030835
TI  - Sclerostin in CKD-MBD: one more paradoxical bone protein?

PMID- 24030836
TI  - Interfacial ultramorphology evaluation of resin luting cements to dentin: a
      correlative scanning electron microscopy and transmission electron microscopy
      analysis.
AB  - The objective of this study was to analyze the dentin-resin cements interfacial
      ultramorphologies using two different methods: scanning (SEM) and transmission
      electron microscopy (TEM). Four commercial products were evaluated: two
      conventional cementing system (RelyX ARC/AdperTM ScotchbondTM Multi-Purpose Plus,
      3M ESPE and Clearfil Esthetic Cement/DC Bond, Kuraray) and two self-adhesive
      resin cements (RelyX Unicem, 3M ESPE and Clearfil SA Cement, Kuraray).
      Prepolymerized resin disks (Sinfony, 3M ESPE) were cemented on oclusal dentin
      surfaces of 24 third human molars, simulating the indirect restorations. After 24
      h, teeth were sectioned into 0.9-mm thick slabs and processed for microscopy
      analyses (SEM or TEM/ n = 3). Qualitative characterization of dentin-resin cement
      interface was performed. Hybrid layer formation with long and dense resin tags
      was observed only for RelyX ARC cementing system. Clearfil Esthetic Cement/DC
      Bond system revealed few and short resin tags formation, whereas no hybridization
      and resin tags were detected for self-adhesive resin cements. Some interfacial
      regions exhibited that the self-adhesive resin cements were not bonded to dentin,
      presenting bubbles or voids at the interfaces. In conclusion, TEM and SEM bonding
      interface analyses showed ultramorphological variations among resin cements,
      which are directly related to dental bonding strategies used for each resin
      cement tested.

PMID- 24030841
TI  - Percutaneous transluminal pulmonary valvuloplasty in a child with tricuspid
      atresia, ventricular septal defect, and severe pulmonary valve stenosis:
      usefulness of the femoral artery approach.
AB  - Percutaneous transluminal pulmonary valvuloplasty may be indicated in not only
      isolated pulmonary valve stenosis, but also complex congenital heart diseases.
      Because palliative surgery for increasing pulmonary blood flow entails a risk of
      scar formation and immediate postoperative complications, catheter intervention
      is preferred, if possible. However, an acute-angled, twisted, or tortuous access
      route or a small valve orifice occasionally makes it difficult for the catheter
      to reach or cross the target. We succeeded in performing this intervention for
      such a complex stenosis effectively and safely in a patient with tricuspid
      atresia, ventricular septal defect (VSD), and severe pulmonary valve stenosis,
      thereby evading surgery. In previous reports, the catheter for this cardiac
      anomaly was accessed via the femoral vein. In the present case, the catheter was
      advanced through the femoral artery via the aorta, left ventricle, VSD, and right
      ventricle to the pulmonary valve, using a micro-catheter in a telescopic manner,
      in combination with a coronary balloon dilatation catheter. This maneuver, which
      has not been reported previously, made it much easier to perform the procedure as
      compared to the femoral vein approach, despite the acute turn and the pinhole
      orifice. Moreover, reported complications of the femoral vein approach, including
      bradycardia, hypotension, and valve regurgitation, were not observed in this
      case. We conclude that the femoral artery approach can be a safe and effective
      alternative in patients for whom a more conventional procedure has been
      unsuccessful.

PMID- 24030840
TI  - Towards elimination of the dark-rim artifact in first-pass myocardial perfusion
      MRI: removing Gibbs ringing effects using optimized radial imaging.
AB  - PURPOSE: Subendocardial dark-rim artifacts (DRAs) remain a major concern in first
      pass perfusion (FPP) myocardial MRI and may lower the diagnostic accuracy for
      detection of ischemia. A major source of DRAs is the "Gibbs ringing" effect. We
      propose an optimized radial acquisition strategy aimed at eliminating ringing
      induced DRAs in FPP. THEORY AND METHODS: By studying the underlying point spread
      function (PSF), we show that optimized radial sampling with a simple
      reconstruction method can eliminate the oscillations in the PSF that cause
      ringing artifacts. We conducted realistic MRI phantom experiments and in vivo
      studies (n = 12 healthy humans) to evaluate the artifact behavior of the proposed
      imaging scheme in comparison to a conventional Cartesian imaging protocol.
      RESULTS: Simulations and phantom experiments verified our theoretical
      expectations. The in vivo studies showed that optimized radial imaging is capable
      of significantly reducing DRAs in the early myocardial enhancement phase (during
      which the ringing effect is most prominent and may obscure perfusion defects)
      while providing similar resolution and image quality compared with conventional
      Cartesian imaging. CONCLUSION: The developed technical framework and results
      demonstrate that, in comparison to conventional Cartesian techniques, optimized
      radial imaging with the proposed optimizations significantly reduces the
      prevalence and spatial extent of DRAs in FPP imaging.

PMID- 24030842
TI  - Questionable reversal of anticoagulation in the therapeutic management of
      cerebral haemorrhage associated with vitamin K antagonists.
AB  - Reversal of anticoagulation is recommended to correct the international
      normalised ratio (INR) for patients with intracranial haemorrhage (ICH)
      associated with vitamin K antagonists (VKA). However, the validity of such
      treatment is debated. We sought to identify, prospectively, the prognostic effect
      of VKA-ICH treatment in a cohort of patients (n=71; median age 78 years, range 20
      89; 52% males). Data collated were: baseline characteristics, treatments,
      baseline and post-treatment INR, haematoma volume, and haematoma enlargement.
      Treatment effects and prognostic factor assessment were in relation to mortality
      and functional outcomes. On admission, the patients had a median score of 9 [p25;
      p75 of 5; 20] on the National Institute of Health Stroke Scale (NIHSS) and a mean
      INR of 2.7 (range: 0.9 - 10.8). Haematoma volume (34.6 cm3; SD: 24.9) correlated
      with NIHSS (r = 0.55; p<0.001) but not with INR. Anticoagulation reversal
      treatment was administered in 83% of patients. INR <1.5 was achieved in 60.7% of
      cases. Death or dependency at three months was 76%. Neither baseline INR,
      anticoagulation reversal nor haematoma enlargement were related to mortality or
      functional outcome. The only independent prognostic factor was clinical severity
      on admission. Baseline NIHSS predicted mortality (OR: 1.18; 95%CI: 1.09-1.27),
      independence (OR: 0.83; 95%CI: 0.74-0.94) and neurological recovery (NIHSS 0-1)
      (OR: 0.83; 95%CI: 0.73-0.95). The data indicate that VKA-ICH had a poor
      prognosis. Treatment and INR correction did not appear to affect outcomes. 

PMID- 24030843
TI  - [Management of decompensated liver cirrhosis in the intensive care unit].
AB  - Liver cirrhosis is the end-stage of long-standing chronic liver diseases. The
      occurrence of complications from liver cirrhosis increases the mortality risk,
      but the prognosis can be improved by optimal management in the intensive care
      unit (ICU). Defined diagnostic algorithms allow the etiology and presence of
      typical complications upon presentation to the ICU to be identified. Acute
      variceal bleeding requires endoscopic intervention, vasoactive drugs,
      antibiotics, supportive intensive care measures and, where necessary, urgent
      transjugular intrahepatic portosystemic shunt (TIPS) procedure. Spontaneous
      bacterial peritonitis needs to be diagnosed and immediately treated in patients
      with ascites. Hepatorenal syndrome should be treated by albumin and terlipressin.
      In case of respiratory failure, differential diagnosis should not only consider
      pneumonia, pulmonary embolism and cardiac failure, but also hepatic hydrothorax,
      portopulmonary hypertension and hepatopulmonary syndrome. The feasibility of
      liver transplantation should be always discussed in patients with decompensated
      cirrhosis. Artificial liver support devices may only serve as a bridging
      procedure until transplant. 

PMID- 24030844
TI  - Ejection fractions and pressure-heart rate product to evaluate cardiac
      efficiency. Continuous, real-time diagnosis using blood pressure and heart rate.
AB  - INTRODUCTION: Ejection fractions, derived from ventricular volumes, and double
      product, related to myocardial oxygen consumption, are important diagnostic
      parameters, as they describe the efficiency with which oxygen is consumed.
      Present technology often allows only intermittent determination of physiological
      status. This deficiency may be overcome if ejection fractions and myocardial
      oxygen consumption could be determined from continuous blood pressure and heart
      rate measurements. The purpose of this study is to determine the viability of
      pressure-derived ejection fractions and pressure-heart rate data in a diverse
      patient population and the use of ejection fractions to monitor patient safety.
      METHODS: Volume ejection fractions, derived from ventricular volumes, EF(V), are
      defined by the ratio of the difference of end-diastolic volume, EDV, and end
      systolic volume, ESV, to EDV. In analogy, pressure ejection fraction, EF(P), may
      be defined by the ratio of the difference of systolic arterial pressure, SBP, and
      diastolic arterial pressure, DBP, to SBP. The pressure-heart rate (heart rate:
      HR) is given by the product of systolic pressure and heart rate, SBP * HR. EF(P)
      and SBP * HR data were derived for all patients (n = 824) who were admitted in
      2008 to the ICU of a university hospital at the specific time 30 min prior to
      leaving the ICU whether as survivors or non-survivors. The results are displayed
      in an efficiency/pressure-heart rate diagram. RESULTS: The efficiency/pressure
      heart rate diagram reveals one subarea populated exclusively by survivors,
      another subarea populated statistically significant by non-survivors, and a third
      area shared by survivors and non-survivors. DISCUSSION AND CONCLUSION: The
      efficiency/pressure-heart rate product relationship may be used as an outcome
      criterion to assess survival and to noninvasively monitor improvement or
      deterioration in real time to improve safety in patients with diverse
      dysfunctions.

PMID- 24030845
TI  - [New recommendations of the Surviving Sepsis Campaign. What is really new?].

PMID- 24030846
TI  - Detection of environmental sources of Histoplasma capsulatum in Chiang Mai,
      Thailand, by nested PCR.
AB  - Histoplasmosis is a systemic mycosis caused by inhaling spores of Histoplasma
      capsulatum, a dimorphic fungus. This fungus grows in soil contaminated with bat
      and avian excreta. Each year, patients with disseminated histoplasmosis have been
      diagnosed in Chiang Mai, northern Thailand. No published information is currently
      available on the environmental sources of this fungus in Chiang Mai or anywhere
      else in Thailand. The aim of this study was to detect H. capsulatum in soil
      samples contaminated with bat guano and avian droppings by nested PCR. Two
      hundred and sixty-five samples were collected from the following three sources:
      soil contaminated with bat guano, 88 samples; soil contaminated with bird
      droppings, 86 samples; and soil contaminated with chicken droppings, 91 samples.
      Genomic DNA was directly extracted from each sample, and H. capsulatum was
      detected by nested PCR using a primer set specific to a gene encoding 100-kDa
      like protein (HcI, HcII and HcIII, HcIV). Histoplasma capsulatum was detected in
      seven of 88 soil samples contaminated with bat guano, one of 21 soil samples
      contaminated with pigeon droppings and 10 of 91 soil samples contaminated with
      chicken droppings. The results indicate the possibility of the association of bat
      guano and chicken droppings with H. capsulatum in this area of Thailand. 

PMID- 24030847
TI  - A matrix approach to guide IHC-based tissue biomarker development in oncology
      drug discovery.
AB  - Immunohistochemistry (IHC) is a core platform for the analysis of tissue samples,
      and there is an increasing demand for reliable and quantitative IHC-based tissue
      biomarkers in oncology clinical research and development (R&D) environments.
      Biomarker assay and drug development proceed in parallel. Furthermore, biomarker
      assay requirements change with each phase of drug development. We have therefore
      developed a matrix tool to enable researchers to evaluate whether a particular
      IHC biomarker assay is fit for purpose. Experience gained from the development of
      130 IHC biomarkers, supporting a large number of oncology drug projects, was used
      to formulate a practical approach to IHC assay development. The resultant matrix
      grid and accompanying work flow incorporates 16 core decision points that link
      antibody and assay specificity and sensitivity, and assay performance in
      preclinical and clinical samples, with stages of drug development. The matrix
      provides a means to ensure that relevant information on an IHC assay in
      development is recorded and communicated consistently and that minimum assay
      validation requirements are met.

PMID- 24030848
TI  - On social polarization and ordinal variables: the case of self-assessed health.
AB  - Social polarization refers to the measurement of the distance between different
      social groups, defined on the basis of variables such as race, religion, or
      ethnicity. We propose two approaches to measuring social polarization in the case
      where the distance between groups is based on an ordinal variable, such as self
      assessed health status. The first one, the 'stratification approach', amounts to
      assessing the degree of non-overlapping of the distributions of the ordinal
      variable between the different population subgroups that are distinguished. The
      second one, the 'antipodal approach', considers that the social polarization of
      an ordinal variable will be maximal if the individuals belonging to a given
      population subgroup are in the same health category, this category corresponding
      either to the lowest or to the highest health status. An empirical illustration
      is provided using the 2009 cross-sectional data of the European Union Statistics
      on Income and Living Conditions (EU-SILC). We find that Estonia, Latvia, and
      Ireland have the highest degree of social polarization when the ordinal variable
      under scrutiny refers to self-assessed health status and the (unordered)
      population subgroups to the citizenship of the respondent whereas Luxembourg is
      the country with the lowest degree of social polarization in health. 

PMID- 24030849
TI  - A redox-active porous coordination network film based on a Ru complex as a
      building block on an ITO electrode.
AB  - The combination of self-assembled monolayer (SAM) and layer-by-layer (LbL) growth
      methods for the construction of a surface porous film has the potential to
      incorporate a wide range of chemical functionalities on a solid surface. A novel
      redox-active Ru complex with 2,6-bis(N-pyridylbenzimidazolyl)-pyridine ligands
      (Ru complex 1), in which four peripheral pyridine groups act as coordination
      sites, was used as a building block for a porous coordination network film. By
      using (4-pyridyl)phenylphosphonic acid as a SAM primer layer on an ITO surface,
      the Ru complex 1 was immobilized by the successive reaction of PdCl2 on the ITO
      electrode in the LbL growth method. Multilayer growth was monitored by UV-vis
      spectra and cyclic voltammetry, in which the linear increases of both absorbance
      and the peak current were observed. This result indicated that the regular
      accumulation of Ru complex 1 onto the ITO surface took place. The permselectivity
      of the present porous coordination network structure was examined using redox
      active molecular probes with different sizes and charges such as ferrocene,
      trimethylaminomethylferrocene, the Os bis(2,6-bis(N-methylbenzimidazolyl)
      pyridine) complex, and tetrathiofulvarene (TTF). With the Os complex and cationic
      ferrocene, only the catalytic peak was observed as a prewave of the adsorbed
      Ru(II/III) peak at +0.73 V. On the other hand, the oxidation peak of ferrocene
      was observed around 0 V vs. Fc(+)/Fc even for nine-layered films in addition to
      the adsorbed Ru(II/III) peak. From these results, not only molecular size but
      also electrostatic interaction plays an important role in the permeation into the
      Ru complex 1 porous network film.

PMID- 24030837
TI  - The effects of stress on physical activity and exercise.
AB  - BACKGROUND: Psychological stress and physical activity (PA) are believed to be
      reciprocally related; however, most research examining the relationship between
      these constructs is devoted to the study of exercise and/or PA as an instrument
      to mitigate distress. OBJECTIVE: The aim of this paper was to review the
      literature investigating the influence of stress on indicators of PA and
      exercise. METHODS: A systematic search of Web of Science, PubMed, and SPORTDiscus
      was employed to find all relevant studies focusing on human participants. Search
      terms included "stress", "exercise", and "physical activity". A rating scale (0
      9) modified for this study was utilized to assess the quality of all studies with
      multiple time points. RESULTS: The literature search found 168 studies that
      examined the influence of stress on PA. Studies varied widely in their
      theoretical orientation and included perceived stress, distress, life events, job
      strain, role strain, and work-family conflict but not lifetime cumulative
      adversity. To more clearly address the question, prospective studies (n = 55)
      were considered for further review, the majority of which indicated that
      psychological stress predicts less PA (behavioral inhibition) and/or exercise or
      more sedentary behavior (76.4 %). Both objective (i.e., life events) and
      subjective (i.e., distress) measures of stress related to reduced PA. Prospective
      studies investigating the effects of objective markers of stress nearly all
      agreed (six of seven studies) that stress has a negative effect on PA. This was
      true for research examining (a) PA at periods of objectively varying levels of
      stress (i.e., final examinations vs. a control time point) and (b) chronically
      stressed populations (e.g., caregivers, parents of children with a cancer
      diagnosis) that were less likely to be active than controls over time. Studies
      examining older adults (>50 years), cohorts with both men and women, and larger
      sample sizes (n > 100) were more likely to show an inverse association. 85.7 % of
      higher-quality prospective research (>= 7 on a 9-point scale) showed the same
      trend. Interestingly, some prospective studies (18.2 %) report evidence that PA
      was positively impacted by stress (behavioral activation). This should not be
      surprising as some individuals utilize exercise to cope with stress. Several
      other factors may moderate stress and PA relationships, such as stages of change
      for exercise. Habitually active individuals exercise more in the face of stress,
      and those in beginning stages exercise less. Consequently, stress may have a
      differential impact on exercise adoption, maintenance, and relapse. Preliminary
      evidence suggests that combining stress management programming with exercise
      interventions may allay stress-related reductions in PA, though rigorous testing
      of these techniques has yet to be produced. CONCLUSIONS: Overall, the majority of
      the literature finds that the experience of stress impairs efforts to be
      physically active. Future work should center on the development of a theory
      explaining the mechanisms underlying the multifarious influences of stress on PA
      behaviors.

PMID- 24030850
TI  - Lamivudine monotherapy in chronic hepatitis B patients from the Indian
      subcontinent: antiviral resistance mutations and predictive factors of treatment
      response.
AB  - BACKGROUND AND OBJECTIVE: Management of chronic hepatitis B is a global public
      health challenge. There are several updated guidelines proposed based on
      treatment outcome data from the respective study populations. In this study, we
      aim to characterize the antiviral resistance mutations to lamivudine monotherapy
      in patients diagnosed with chronic hepatitis B from the Indian subcontinent.
      METHODS: A total of 147 lamivudine-treated patients with a median treatment
      duration of 13 (interquartile range 8-24) months were studied. Virological
      response was measured by hepatitis B virus (HBV) DNA levels. Antiviral resistance
      mutations were identified by sequencing HBV reverse transcriptase domains.
      Factors associated with virological response and antiviral resistance mutations
      were analyzed. RESULTS: Virological response was observed in 50 (35 %) patients
      while 84 (57 %) were non-responders. The virological response for the remaining
      13 (9 %) patients was undetermined. Forty patients (27 %) developed lamivudine
      resistant mutations. HBV genotypes, subgenotypes and hepatitis B surface antigen
      subtypes did not show significant association with virological response or
      lamivudine-resistant mutations. High HBV DNA levels and increased treatment
      duration were strongly associated with the development of lamivudine-resistant
      mutations (p = 0.002 and p < 0.001). Patients who continued to be positive for
      hepatitis B e antigen have an increased risk for treatment failure (p = 0.010).
      High baseline aspartate transaminase levels were significantly associated with
      subsequent lamivudine response (p = 0.037). CONCLUSION: Considering the limited
      potency and high resistance rates to lamivudine therapy, our study emphasizes the
      use of more potent drugs in the management of chronic hepatitis B in the Indian
      subcontinent.

PMID- 24030851
TI  - Alterations of C-MYC, NKX3.1, and E-cadherin expression in canine prostate
      carcinogenesis.
AB  - The dog (canis lupus familiaris) is the only other species besides humans that
      develop spontaneous prostatic carcinomas (PCa) at a high frequency. The canine
      model is primarily utilized for the study of the PCa molecular mechanisms and
      provides a natural animal model for the study of potential therapies. In humans,
      the PCa frequently exhibits mutations in the C-MYC and a reduced expression of
      the E-cadherin and NKX3.1 proteins. This study's objective was to evaluate the
      NKX3.1, C-MYC, and E-cadherin expression in the canine normal prostate, benign
      prostatic hyperplasia (BPH), proliferative inflammatory atrophy (PIA) and PCa and
      to verify differences in expression and subcellular localization of these
      proteins in the prostatic carcinogenesis. A tissue microarray (TMA) slide was
      constructed, and immunohistochemistry with antibodies raised against C-MYC,
      NKX3.1, E-cadherin and p63 was performed using the peroxidase and DAB methods.
      The C-MYC protein expression was elevated in the cytoplasm and nuclei of the
      canine PCa and PIA compared with the normal prostate (P = 0.004. The NKX3.1
      protein expression was reduced in 94.75% of the PCa and 100% of the PIA compared
      with the normal prostate (P = 0.0022). In fact, the expression of E-cadherin
      trended towards a decrease in carcinomas when compared to normal prostate and
      PIA. By immunohistochemistry, more p63-positive basal cells were observed in the
      PCa and PIA when compared with the normal prostate (P = 0.0002). This study has
      demonstrated that the carcinogenesis of canine prostatic tissue may be related to
      basal cell proliferation, the gain of C-MYC function and the loss of NKX3.1
      protein expression.

PMID- 24030852
TI  - Selective functionalization of the protein N terminus with N-myristoyl
      transferase for bioconjugation in cell lysate.
AB  - A site to behold: Robust site-specific functionalization of engineered proteins
      is achieved with N-myristoyl transferase (NMT) in bacterial cells. NMT tolerates
      non-natural substrate proteins as well as reactive fatty acid tags, rendering it
      a powerful tool for protein conjugation applications, including the construction
      of protein microarrays from lysate. 

PMID- 24030853
TI  - Vibrant soundbridge in aural atresia: does severity matter?
AB  - Congenital aural atresia (CAA) poses significant challenges to surgical
      remediation. Both bone anchored hearing aids (BAHA) and the Vibrant Soundbridge
      (VSB) have been considered as alternatives or adjuncts to conventional
      atresiaplasty. A consensus statement on VSB implantation in children and
      adolescents recommended against implantation when the Jahrsdoerfer score was less
      than 8. More recent publications suggest that patients with Jahrsdoerfer scores
      between three and seven may benefit from VSB implantation. The purpose of this
      study was to further investigate the outcomes of VSB implantation in CAA. The
      study was a multi-center, retrospective review. A retrospective review of data
      (patient's demographic, clinical, implant and audiological information) from four
      collaborating centers that have performed VSB implantation in CAA was performed.
      Outcomes based on severity of the atresia using the Jahrsdoerfer and Yellon
      Branstetter scoring systems were also evaluated. Data from 28 patients from the
      four centers revealed no iatrogenic facial nerve injuries or change in bone
      thresholds. Post-operative speech threshold and speech recognition was,
      respectively, 39 dB and 94%. Jahrsdoerfer and Yellon scores ranged from 4 to 9
      and 4 to 12, respectively. The scores did not correlate to or predict outcomes.
      Three individual elements of the scores did correlate to initial, but not long
      term outcomes. Atresiaplasty and BAHA in the management of CAA are not complete
      solutions. VSB may offer an alternative in these surgically complex patients for
      achieving amplification, though better metrics for patient selection need to be
      developed. LEVEL OF EVIDENCE : IV.

PMID- 24030854
TI  - Clinical implication landmark: noninvasive quantification of fractional flow
      reserve evaluating interventional therapy.

PMID- 24030855
TI  - Quantitative wearable sensors for objective assessment of Parkinson's disease.
AB  - There is a rapidly growing interest in the quantitative assessment of Parkinson's
      disease (PD)-associated signs and disability using wearable technology. Both
      persons with PD and their clinicians see advantages in such developments.
      Specifically, quantitative assessments using wearable technology may allow for
      continuous, unobtrusive, objective, and ecologically valid data collection. Also,
      this approach may improve patient-doctor interaction, influence therapeutic
      decisions, and ultimately ameliorate patients' global health status. In addition,
      such measures have the potential to be used as outcome parameters in clinical
      trials, allowing for frequent assessments; eg, in the home setting. This review
      discusses promising wearable technology, addresses which parameters should be
      prioritized in such assessment strategies, and reports about studies that have
      already investigated daily life issues in PD using this new technology.

PMID- 24030856
TI  - Factors affecting clinical outcome following treatment of early childhood caries
      under general anaesthesia: a two-year follow-up.
AB  - AIM: To investigate factors that might affect the clinical outcome of early
      childhood caries treatment under dental general anaesthesia (DGA). DESIGN:
      Retrospective longitudinal study. The medical records of paediatric patients with
      early childhood caries who underwent full dental rehabilitation under DGA during
      2011 in a private medical facility in Jeddah, Saudi Arabia, were investigated.
      Study parameters were the patient's financial arrangements and compliance with
      suggested recall plan. Statistical analysis of caries recurrence and the need to
      repeat the rehabilitation process was also performed. RESULTS: Eighteen percent
      failed to attend any post-operative visit. Twenty-six percent did not comply with
      the post-operative preventive plan. The overall relapse rate was high (58.5%),
      with the highest percentage (68%) among the non-compliant group. The highest
      frequency of repeat DGA (10%) was in the non-compliant group. CONCLUSIONS:
      Despite the high rate of post-operative caries recurrence, DGA is still an
      acceptable treatment option as it minimises the need for future dental treatment.
      Compliance by caregivers with post-operative care plans is as important as the
      procedure itself. In Saudi Arabia, targeting the actual caregivers with post
      operative dental health education presents challenges that might affect the
      clinical outcome of DGA.

PMID- 24030857
TI  - [Anesthesia in the angiography suite : More than dancing in the dark].

PMID- 24030859
TI  - Putting the right spin on it.

PMID- 24030861
TI  - The effects of PTSD symptoms on health care resource utilization in a low-income,
      urban primary care setting.
AB  - Individuals with posttraumatic stress disorder (PTSD) symptoms engage in greater
      rates of health care utilization. Existing literature is limited, however,
      because the number of visits to health care providers is exclusively used as an
      outcome. Low-income women (N = 96) screening positive for PTSD symptoms (n = 23;
      23.9%) were compared to those who did not (n = 73) on a range of health care
      utilization outcomes obtained through a chart review. Significant PTSD symptoms
      were associated with more complaints per visit, ordered labs, and prescribed
      medications--beyond the effects of age, depression symptoms, and chronic illness.
      Individuals with PTSD symptoms are a challenge to primary care as currently
      practiced. Collaboration with mental health professionals and specific primary
      care procedures to diagnose and treat PTSD are needed.

PMID- 24030860
TI  - Through the glass darkly: intraepithelial neoplasia, top-down differentiation,
      and the road to ovarian cancer.
AB  - It is currently hoped that deaths from extra-uterine high-grade serous cancer
      (HGSC) will be reduced via opportunistic salpingectomy in healthy women.
      Accumulated data implicate the fimbria as a site of origin and descriptive
      molecular pathology and experimental evidence strongly support a serous
      carcinogenic sequence in the Fallopian tube. Both direct and indirect
      ('surrogate') precursors suggest that the benign tube undergoes important
      biological changes after menopause, acquiring abnormalities in gene expression
      that are often shared with malignancy, including PAX2, ALDH1, LEF1, RCN1, RUNX2,
      beta-catenin, EZH2, and others. However, the tube can be linked to only some
      HGSCs, recharging arguments that nearby peritoneum/ovarian surface epithelium
      (POSE) also hosts progenitors to this malignancy. A major sticking point is the
      difference in immunophenotype between POSE and Mullerian epithelium, essentially
      requiring mesothelial to Mullerian differentiation prior to or during malignant
      transformation to HGSC. However, emerging evidence implicates an embryonic or
      progenitor phenotype in the adult female genital tract with the capacity to
      differentiate, normally or during neoplastic transformation. Recently, a putative
      cell of origin for cervical cancer has been identified in the squamo-columnar
      (SC) junction, projecting a model whereby Krt7+ embryonic progenitors give rise
      to immunophenotypically distinct progeny under stromal influences via 'top down'
      differentiation. Similar differentiation can be seen in the endometrium with a
      parallel in juxtaposed mesothelial and Mullerian differentiation in the ovary.
      Abrupt mesothelial-Mullerian transitions remain to be proven, but would explain
      the rapid evolution, short asymptomatic interval, and absence of a defined
      epithelial starting point in many HGSCs. Resolving this question will require
      accurately distinguishing progenitor from progeny tumour cells in HGSC and
      pinpointing where initial transformation and trans-differentiation occur, whether
      in the tube or POSE. Both will be critical to expectations from prophylactic
      salpingectomy and future approaches to pelvic serous cancer prevention.

PMID- 24030862
TI  - Functionalisation and surface modification of electrospun polylactic acid
      scaffold for tissue engineering.
AB  - Repair or replacement of damaged tissues using tissue engineering technology is
      considered to be a fine solution for enhanced treatment of different diseases
      such as skin diseases. Although the nanofibers made of synthetic degradable
      polymers, such as polylactic acid (PLA), have been widely used in the medical
      field, they do not favour cellular adhesion and proliferation. To enhance cell
      adherence on scaffold and improve biocompatibility, the surface of PLA scaffold
      was modified by gelatin in our experiments. For electrospinning, PLA and gelatin
      were dissolved in hexafluoroisopropanol (HFIP) solvent at varying compositions
      (PLA:gelatin at 3:7 and 7:3). The properties of the blending nanofiber scaffold
      were investigated by Fourier transform infrared (FT-IR) spectroscopy and scanning
      electron microscopy (SEM). Modified PLA/gelatin 7/3 scaffold is more suitable for
      fibroblasts attachment and viability than the PLA or gelatin nanofiber alone.
      Thus fibroblast cultured on PLA/gelatin scaffold could be an alternative way to
      improve skin wound healing. 

PMID- 24030863
TI  - Outcomes in diabetic patients undergoing primary percutaneous coronary
      intervention for acute anterior myocardial infarction: results from the INFUSE
      AMI study.
AB  - OBJECTIVES: To evaluate the clinical, angiographic, and cardiac magnetic
      resonance imaging (cMRI) results in patients with and without diabetes mellitus
      (DM) undergoing primary percutaneous coronary intervention (PCI) for ST-elevation
      myocardial infarction (STEMI). BACKGROUND: DM has been associated with increased
      mortality in patients with STEMI, yet the mechanisms underpinning this
      association have not been completely elucidated. METHODS: Overall, 451 patients
      (51 diabetics) from the INFUSE-AMI trial were studied. They presented with an
      anterior STEMI due to an occluded left anterior descending artery (LAD) and
      underwent bivalirudin-supported primary PCI with or without intralesion abciximab
      and with or without thrombus aspiration. Angiographic baseline and post-procedure
      parameters, cMRI at 30 days, and clinical follow-up at 30 days and at 1 year were
      compared between diabetic and nondiabetic patients. RESULTS: Patients with DM had
      significantly more comorbidities and more extensive LAD disease than
      nondiabetics. Primary PCI was equally effective in restoring coronary flow in
      both groups and the infarct size at 30 days was similar (14.3% [7.1, 24.5] vs.
      17.3% [8.1, 23.6], respectively, P = 0.55). Diabetic patients had more major
      cardiovascular and cerebrovascular events at 1 year (16.5% vs. 8.0%, P = 0.04).
      Stent thrombosis within 30 days after primary PCI was higher in diabetic than in
      nondiabetic subjects (4.3% vs. 0.8%, P = 0.03). CONCLUSIONS: Patients with DM
      presenting with STEMI had a higher baseline risk profile than those without DM.
      Although reperfusion success and infarct size were similar, diabetic patients
      experienced more death, reinfarction, stent thrombosis, and revascularization
      than nondiabetics.

PMID- 24030864
TI  - Posterior pharyngeal candidiasis in the absence of clinically overt oral
      involvement: a cross-sectional study.
AB  - PURPOSE: Although oropharyngeal candidiasis is associated with inhaled
      corticosteroid (ICS) usage, there is sparse data on the prevalence of posterior
      pharyngeal candidiasis in those without any detectable oral candidiasis on
      clinical examination. We systematically investigated the relationship between
      oral candidiasis on clinical examination and the presence of posterior pharyngeal
      candidiasis at bronchoscopy. METHODS: We conducted a cross-sectional study on a
      convenience sample of 100 patients undergoing bronchoscopy at our institution.
      Patients were assessed for symptoms of and risk factors for candida infection and
      had an examination of their oropharynx for evidence of candidiasis before
      bronchoscopy. They subsequently had a detailed assessment for posterior
      candidiasis at bronchoscopy. We performed a posteriori subgroup analysis, which
      focused solely on those patients on ICS maintenance therapy. RESULTS: Median age
      was 54.7 (27-84) years, and 55 patients were male; 47 % of patients were on ICS,
      and 20 % of this cohort received recent oral corticosteroids. Twenty-eight
      percent of this convenience sample had posterior pharyngeal candidiasis; however,
      only 10.7 % (3/28) of these patients had clinically detectable oral candidiasis
      on clinical examination before bronchoscopy. Factors that were independently
      associated with the presence of pharyngeal candidiasis at bronchoscopy were OR
      (95 % CI) ICS usage 6.9 (2.5-19.2), particularly fluticasone usage 6.8 (2.62
      17.9) and the presence of dysphonia 3.2 (1.3-8.0). In the subgroup analysis of
      ICS usage, posterior pharyngeal candidiasis was correlated with the presence of
      dysphonia but was not independently associated with fluticasone or budesonide
      dosage. CONCLUSIONS: This study demonstrates that posterior pharyngeal
      candidiasis in the absence of clinically overt oral candidiasis is frequent
      amongst ICS users. A history of ICS use, particularly fluticasone usage, as well
      as the presence of dysphonia are associated with posterior pharyngeal candidiasis
      at bronchoscopy, even in the absence of clinically overt oral involvement.

PMID- 24030865
TI  - Ultrasound-assisted magnetic SPE based on Fe3O4-grafted graphene for the
      determination of polychlorinated biphenyls in water samples.
AB  - An ultrasound-assisted magnetic SPE procedure with an Fe3 O4 -grafted graphene
      nanocomposite as the magnetic adsorbent has been developed to determine seven
      polychlorinated biphenyls (PCBs; PCB28, PCB52, PCB101, PCB118, PCB138, PCB153,
      and PCB180) simultaneously in 200 mL environmental water samples, in combination
      with GC-MS/MS. Several factors related to magnetic SPE efficiencies, such as the
      superparamagnetic intensity and amount of adsorbent, extraction time, sample pH,
      and desorption conditions were investigated. With the assistance of ultrasound,
      the extraction achieved the maximum within only 20 s, attributed to the powerful
      adsorptive ability of the magnetic adsorbent toward the PCBs. Under the optimized
      conditions, an excellent linearity was observed in the range of 0.1-100 ng/L for
      PCB28, 0.2-100 ng/L for PCB52, and 0.5-100 ng/L for the other five PCBs with the
      correlation coefficients ranging from 0.9988 to 0.9996. The mean recoveries at
      spiked levels of 5.0 and 10.0 ng/L were 84.9-108.5%, the coefficients of
      variations were <6.5%. With convenient magnetic separation, the synthesized
      magnetic adsorbent could be recycled more than ten times. The proposed method was
      demonstrated to be feasible, simple, rapid, and easy to operate for the trace
      analysis of the PCBs in environmental water samples. 

PMID- 24030866
TI  - Prevalence of, and risk factors for, HIV, hepatitis B and C infections among men
      who inject image and performance enhancing drugs: a cross-sectional study.
AB  - OBJECTIVE: To describe drug use, sexual risks and the prevalence of blood-borne
      viral infections among men who inject image and performance enhancing drugs
      (IPEDs). DESIGN: A voluntary unlinked-anonymous cross-sectional biobehavioural
      survey. SETTING: 19 needle and syringe programmes across England and Wales.
      PARTICIPANTS: 395 men who had injected IPEDs. RESULTS: Of the participants
      (median age 28 years), 36% had used IPEDs for <5 years. Anabolic steroids (86%),
      growth hormone (32%) and human chorionic gonadotropin (16%) were most frequently
      injected, with 88% injecting intramuscularly and 39% subcutaneously. Two-thirds
      also used IPEDs orally. Recent psychoactive drug use was common (46% cocaine, 12%
      amphetamine), 5% had ever injected a psychoactive drug and 9% had shared
      injecting equipment. 'Viagra/Cialis' was used by 7%, with 89% reporting
      anal/vaginal sex in the preceding year (20% had 5+ female-partners, 3% male
      partners) and 13% always using condoms. Overall, 1.5% had HIV, 9% had antibodies
      to the hepatitis B core antigen (anti-HBc) and 5% to hepatitis C (anti-HCV). In
      multivariate analysis, having HIV was associated with: seeking advice from a
      sexual health clinic; having had an injection site abscess/wound; and having male
      partners. After excluding those reporting male partners or injecting psychoactive
      drugs, 0.8% had HIV, 8% anti-HBc and 5% anti-HCV. Only 23% reported uptake of the
      hepatitis B vaccine, and diagnostic testing uptake was poor (31% for HIV, 22% for
      hepatitis C). CONCLUSIONS: Previous prevalence studies had not found HIV among
      IPED injectors. HIV prevalence in this, the largest study of blood-borne viruses
      among IPED injectors, was similar to that among injectors of psychoactive drugs.
      Findings indicate a need for targeted interventions.

PMID- 24030867
TI  - Stakeholder experiences with general practice pharmacist services: a qualitative
      study.
AB  - OBJECTIVES: To explore general practice staff, pharmacist and patient experiences
      with pharmacist services in Australian general practice clinics within the
      Pharmacists in Practice Study. DESIGN: Qualitative study. SETTING: Two general
      practice clinics in Melbourne, Australia, in which pharmacists provided
      medication reviews, patient and staff education, medicines information and
      quality assurance services over a 6-month period. PARTICIPANTS: Patients,
      practice staff and pharmacists. METHOD: Semi-structured telephone interviews with
      patients, focus groups with practice staff and semi-structured interviews and
      periodic narrative reports with practice pharmacists. Data were analysed
      thematically and theoretical frameworks used to explain the findings. RESULTS: 34
      participants were recruited: 18 patients, 14 practice staff (9 general
      practitioners, 4 practice nurses, 1 practice manager) and 2 practice pharmacists.
      Five main themes emerged: environment; professional relationships and
      integration; pharmacist attributes; staff and patient benefits and logistical
      challenges. Participants reported that colocation and the interdisciplinary
      environment of general practice enabled better communication and collaboration
      compared to traditional community and consultant pharmacy services. Participants
      felt that pharmacists needed to possess certain attributes to ensure successful
      integration, including being personable and proactive. Attitudinal, professional
      and logistical barriers were identified but were able to be overcome. The
      findings were explained using D'Amour's structuration model of collaboration and
      Roger's diffusion of innovation theory. CONCLUSIONS: This is the first
      qualitative study to explore the experiences of general practice staff,
      pharmacists and patients on their interactions within the Australian general
      practice environment. Participants were receptive of colocated pharmacist
      services, and various barriers and facilitators to integration were identified.
      Future research should investigate the feasibility and sustainability of general
      practice pharmacist roles.

PMID- 24030868
TI  - Binding of a positron to nucleic base molecules and their pairs.
AB  - Hole attack: A theoretical one-electron oxidation of nucleic base molecules and
      their pairs by positron is proposed, based on the calculations for positron
      attached neutral forms of species, adenine (A), thymine (T), guanine (G),
      cytosine (C), and their Watson-Crick base pairs (A-T and G-C). The results reveal
      that binding of a positron to neutral isolated nucleic base molecules is base
      selective. 

PMID- 24030869
TI  - Cortisol and PTSD symptoms among male and female high-exposure 9/11 survivors.
AB  - Only a few studies have examined cortisol response to trauma-related stressors in
      relation to posttraumatic stress disorder (PTSD). We followed a sample of high
      exposure survivors of the attacks on September 11, 2001 (9/11; 32 men and 29
      women) and examined their cortisol response after recalling the escape from the
      attack, 7 and 18 months post-9/11. PTSD symptoms and saliva cortisol levels were
      assessed before and after trauma recollection. Hierarchical regression analyses
      revealed that PTSD symptoms and male sex predicted increased cortisol response
      following recollections. For men, elevated cortisol was associated with greater
      severity of reexperiencing symptoms (p < .001) and lower severity of avoidance
      symptoms (p < .001). For women, recall-induced cortisol was minimal and unrelated
      to PTSD symptoms (p = .164 and p = .331, respectively). These findings suggest
      that augmented cortisol response to trauma-related stressors may be evident in
      men reporting symptoms of PTSD. Thus, as cortisol abnormalities related to PTSD
      symptoms appear sex-specific, future research on mechanisms of sex differences in
      response to trauma is warranted. 

PMID- 24030871
TI  - Inhibition of mTOR signalling potentiates the effects of trichostatin A in human
      gastric cancer cell lines by promoting histone acetylation.
AB  - Deregulation of the mammalian target of rapamycin pathway (mTOR pathway) is
      associated with human cancer. The relationship between mTOR pathway and histone
      acetylation is still unclear in gastric cancer (GC). Immunohistochemistry was
      used to examine the phosphorylation of mTOR and eukaryotic translation initiation
      factor 4E-binding protein 1 (4E-BP1) in GC tissues. MKN45 and SGC7901 cells were
      treated with the mTOR inhibitor rapamycin (RAPA) alone or in combination with the
      phosphatidylinositol 3-kinase inhibitor LY294002 and the histone deacetylase
      (HDAC) inhibitor trichostatin A (TSA). Small interfering RNA (siRNA) technology
      was also used to knockdown mTOR. Phosphorylated mTOR and phosphorylated 4E-BP1
      were expressed in 71.1% and 68.4% of the human GC tissues tested, respectively;
      significantly higher than the levels in para-cancerous tissues (50% and 57.9%)
      and normal tissues (44.6% and 29%). RAPA markedly inhibited cell proliferation,
      induced G1 cell cycle arrest, and reduced phosphorylation of p70 S6 protein
      kinase (p70S6K) and 4E-BP1 in GC cells, particularly when used in combination
      with LY294002 or TSA. The mRNA expression of the tumour suppressor gene p21(WAF1)
      increased significantly in GC cells treated with both RAPA and TSA. Histone
      acetylation also increased after RAPA and TSA treatment or siRNA knockdown of
      mTOR. Our findings suggest that the mTOR pathway is activated in GC, and also
      that inhibition of mTOR enhances the ability of TSA to suppress cell
      proliferation and lead to cell cycle arrest via increasing histone acetylation
      and p21(WAF1) transcription in human MKN45 and SGC7901 GC cells. 

PMID- 24030872
TI  - Studies on binding interactions between clenbuterol hydrochloride and two serum
      albumins by multispectroscopic approaches in vitro.
AB  - In this study, binding properties of clenbuterol hydrochloride (CL) with human
      serum albumin (HSA) and bovine serum albumin (BSA) were examined using constant
      protein concentrations and various CL contents under physiological conditions.
      The binding parameters were confirmed using fluorescence quenching spectroscopy
      at various temperatures. The experimental results confirmed that the quenching
      mechanisms of CL and HSA/BSA were both static quenching processes. The
      thermodynamic parameters, namely, enthalpy change (DeltaH) and entropy change
      (DeltaS), were calculated according to the van't Hoff equation, which suggested
      that the electrostatic interactions were the predominant intermolecular forces in
      stabilizing the CL-HSA complex, and hydrogen bonds and van der Waals force were
      the predominant intermolecular forces in stabilizing the CL-BSA complex.
      Furthermore, the conformational changes of HSA/BSA in the presence of CL were
      determined using the data obtained from three-dimensional fluorescence
      spectroscopy, ultraviolet-visible absorption spectroscopy and circular dichroism
      spectroscopy.

PMID- 24030873
TI  - Combination of supercritical fluid extraction with counter-current chromatography
      to isolate anthocyanidins from the petals of Chaenomeles sinensis based on
      mathematical calculations.
AB  - Supercritical fluid extraction (SFE) coupled with high-speed counter-current
      chromatography (HSCCC) was successfully used for the extraction and on-line
      isolation of the anthocyanidins from the petals of Chaenomeles sinensis in two
      stages. The SFE parameters were optimized by an orthogonal test, and the solvent
      systems of SFE and HSCCC were calculated and optimized with the help of a
      multiexponential function model. In the first stage, the lower phase of the
      solvent system of n-butanol/tert-butyl methyl ether/acetonitrile/0.1% aqueous TFA
      (0.715:1.0:0.134:1.592, v/v/v/v) was used as both the SFE modifier and the HSCCC
      stationary phase, after extraction, the extractants were pumped into HSCCC
      column, and then eluted with the corresponding upper phase to isolate the
      moderately hydrophobic compounds. In the second stage, the upper phase of the
      solvent system of n-butanol/ethyl acetate/acetonitrile/0.1% aqueous TFA
      (1.348:1.0:0.605:2.156, v/v/v/v) was used as both the SFE modifier and the HSCCC
      stationary phase, followed by elution with the corresponding lower phase to
      separate the hydrophobic compounds. With the help of two-stage SFE/HSCCC, six
      compounds including delphinidin-3-O-glucoside (Dp3G), cyanidin-3-O-glucoside
      (Cy3G), peonidin-3-O-glucoside (Pn3G), delphinidin (Dp), peonidin (Pn), and
      malvidin (Mv) were successfully separated within 300 min. The targeted compounds
      were identified by UV spectrophotometry, MS, and NMR spectroscopy. This research
      has opened up great prospects for the industrial application of SFE-HSCCC for the
      automatic extraction and separation of unstable compounds. 

PMID- 24030874
TI  - Comparing key informants to health workers in identifying children in need of
      surgical eye care services.
AB  - The objective of the study was to compare the productivity of key informants
      (KIs) and dedicated health workers (HWs) in identifying children with surgical
      eye care needs. In two regions of Tanzania, KIs and HWs were trained to identify
      and register children with severe visual impairment or blindness, with the
      objective of providing them with surgical eye care services. Identified children
      were examined at predetermined sites. The total numbers of children in need of
      surgical services identified by KIs and HWs were compared to measure their
      relative efficacy. A total of 197 KIs and 63 HWs were trained in the two regions.
      Five hundred and forty-nine children were identified by KIs and 22 children were
      identified by HWs: KIs were three times more productive than the HWs. Most of the
      children identified and examined had serious eye pathology and received surgery
      or low vision services. The cost per child found was significantly less for
      children found by KI compared to HW. The study indicates that, in rural Africa,
      finding children in need of surgical and low vision interventions and ensuring
      that they are properly screened appears to require community-based efforts. 

PMID- 24030875
TI  - Knowledge, attitudes and practices of rabies prevention and dog bite injuries in
      urban and peri-urban provinces in Cambodia, 2009.
AB  - Rabies remains a major public health issue despite the existence of well
      established prevention and treatment protocols. Knowledge and methods of practice
      were evaluated in an urban and peri-urban province of Cambodia (Phnom Penh and
      Kandal, respectively). The majority of respondents (93.2%; 233/250) had heard of
      the disease rabies, of whom only 77.3% (180/233) knew it was fatal to humans. In
      addition, only 51.9% (121/233) were aware of the vaccine for dogs. The proportion
      of the population that reported a dog bite (2004-2009) was similar for Phnom Penh
      and Kandal. Nearly one-half of all victims (37/75) sought treatment at the
      Institut Pasteur-Cambodia (IPC) clinic, followed by a private clinic (19/75), a
      hospital (6/75) and traditional medicine (4/75); 7 victims sought no treatment
      and 2 reported other. Overall, children aged <15 years reported a significantly
      greater proportion of dog bite victims than adults aged >=15 years [10.0%
      (28/280) vs 4.4% (47/1059), respectively]. Nearly all dog owners agreed to pay
      for their dogs' vaccination (96.5%; 136/141) and to use a collar (94.3%;
      133/141). Only 41.8% (59/141) and 51.8% (73/141) would pay to have their dogs
      spayed and neutered, respectively. Further community education on the prevention
      of rabies transmission is needed. Focusing on responsible dog ownership and the
      importance of both the prevention and immediate treatment following a dog bite is
      essential to reduce rabies infection in Cambodia. 

PMID- 24030876
TI  - Nomadic Fulani communities manage malaria on the move.
AB  - As in other public health efforts, the current promotion of insecticide-treated
      net (ITN) usage and prompt treatment of malaria has left the nomadic populations
      behind. The hypothesis that nomads can apply the community-directed intervention
      (CDI) strategy for fever management in children under-5 was tested among nomadic
      Fulani communities in northeastern Nigeria. Twenty camps selected representatives
      who were trained to provide artemisinin-based combination therapy and ITNs to
      their members. Coverage was compared with existing practice in 20 other nomadic
      Fulani communities. At baseline, none of the camps had ITNs, and antimalarial
      usage was only 2.7% in intervention camps and 5.8% in comparison camps. The
      nomads redesigned the negotiated intervention delivery approach to suit their
      culture. Within 12 months antimalarial usage and appropriate management of
      malaria in children under-5 reached 88.0% and 81.7%, respectively, and within 24
      months they reached 87.9% and 86.1%, respectively, surpassing the Roll Back
      Malaria target of 80% coverage by 2011. In contrast, usage was <5% in the
      comparison camps. ITN possession reached 66.7% and 73.2% in the first and second
      years, respectively, within intervention camps, but was unchanged in comparison
      camps. However, ITN usage remained low at 21.7% in the second year (P < 0.05).
      When empowered, nomads will appropriately manage malaria using the CDI approach. 

PMID- 24030877
TI  - Improving health service delivery organisational performance in health systems: a
      taxonomy of strategy areas and conceptual framework for strategy selection.
AB  - Health systems strengthening (HSS) is a priority for global health funders,
      policy-makers and practitioners. Although many HSS efforts have focused on policy
      levers such as financing approaches, payment schemes or regulatory reforms, less
      attention has been directed to targeting the organisations that deliver health
      services such as hospitals, health centres and clinics. Evidence suggests that
      the impact of organisation-level interventions varies by context; however, we
      lack a general framework for integrating organisational context into performance
      improvement strategies for health service delivery organisations. Drawing on open
      systems theories from organisational behaviour and management as well as a review
      of 181 empirical studies of health service delivery organisations in low- and
      middle-income countries, we propose a taxonomy of seven strategy areas for
      improving organisational performance as well as a multistage conceptual framework
      for selecting among them. We propose that the choice of strategy for improving
      health service delivery organisational performance should be informed by: (i) the
      root cause of the organisation's performance gap; (ii) the environmental
      conditions facing the organisation; and (iii) the implementation capability of
      the organisation. We also highlight conditions under which different strategy
      areas may be expected to be optimally effective. The approaches presented in this
      paper offer a way for health system decision-makers and researchers to
      systematically assess and incorporate organisational context in the process of
      developing strategies to improve the performance of health service delivery
      organisations and, ultimately, of health systems. 

PMID- 24030878
TI  - HIV as a risk factor for cardiac disease in Botswana: a cross-sectional study.
AB  - The primary objective of this study was to assess how HIV has influenced the
      spectrum of heart diseases in Botswana and to examine the HIV prevalence among
      patients with cardiomegaly. The secondary objective was to evaluate the value of
      the cardiothoracic (CT) ratio on chest radiography (CXR) as a screening tool for
      cardiac disease. In total, 179 patients (age 14-97 years) with cardiomegaly (all
      CT ratios >0.53 on CXR) and known HIV status were referred to Botswana's sole
      hospital-based echocardiographic centre. Clinical examination and
      echocardiography were performed. Cardiomyopathy (36.9%), pericarditis (21.2%),
      hypertensive heart disease (14.0%), rheumatic heart disease (8.4%) and right
      sided heart failure (6.7%) were the main causes of cardiomegaly; only two
      patients had a normal echocardiogram. The HIV prevalence was higher than in the
      general population [59% vs 25%; relative risk (RR) of HIV infection compared with
      the general population 2.4, 95% CI 2.1-2.7]. HIV infection was strongly
      associated with pericarditis (RR 3.3, 95% CI 2.8-3.8) and cardiomyopathy (RR 2.9,
      95% CI 2.4-3.5). These data suggest an increased risk of non-ischaemic heart
      disease, in particular pericarditis and cardiomyopathy, among HIV-infected
      patients. The CT ratio on CXR had high specificity in detecting severe heart
      disease and can be a useful screening tool in areas with limited resources. 

PMID- 24030879
TI  - Cost-effectiveness analysis of three health interventions to prevent malaria in
      pregnancy in an area of low transmission in Uganda.
AB  - Pregnant women and their unborn children are vulnerable to malaria, increasing
      the risk of maternal anaemia, low birthweight (LBW) and intrauterine growth
      retardation. There is little evidence on the cost-effectiveness of intermittent
      preventive treatment in pregnancy (IPTp) and insecticide-treated bednets (ITN) in
      areas of low transmission. A randomised controlled trial with three arms was
      conducted in antenatal clinics in Kabale District (Uganda), an epidemic-prone
      highland area of low malaria transmission. The interventions were: (i) IPTp with
      sulfadoxine/pyrimethamine (SP) given twice during pregnancy (IPTp-SP); (ii) ITNs
      alone; and (iii) a combined intervention with both ITNs and IPTp-SP. Primary
      health outcomes were LBW and maternal anaemia. The costs of providing IPTp-SP and
      ITNs as well as treatment of malaria episodes were captured from all health
      centres in the study area. There were no significant differences in health
      outcomes among the three interventions. The cost-effectiveness analysis and
      sensitivity analyses performed did not provide convincing support for replacing
      IPTp-SP (current policy) by ITNs alone or by a combined intervention in this low
      transmission setting on economic grounds. The cost per pregnant woman of
      providing the services was lowest for the IPTp-SP intervention (US$0.79 per
      woman) followed by ITNs (US$1.71) and the combined intervention of IPTp-SP + ITNs
      (US$2.48). The relative cost-effectiveness of antenatal distribution of ITNs
      might improve if the cost savings accruing from continued use of a long-lasting
      insecticidal net after pregnancy as well as positive externalities were also
      taken into account, and this warrants further study. [ClinicalTrials.gov
      identifier: NCT00142207]. 

PMID- 24030880
TI  - Approaching the community about screening children for a multicentre malaria
      vaccine trial.
AB  - Community sensitisation, as a component of community engagement, plays an
      important role in strengthening the ethics of community-based trials in
      developing countries and is fundamental to trial success. However, few
      researchers have shared their community sensitisation strategies and experiences.
      We report on our perspective as researchers on the sensitisation activities
      undertaken for a phase II malaria vaccine trial in Kilifi District (Kenya) and
      Korogwe District (Tanzania), with the aim of informing and guiding the
      operational planning of future trials. We report wide variability in recruitment
      rates within both sites; a variability that occurred against a backdrop of
      similarity in overall approaches to sensitisation across the two sites but
      significant differences in community exposure to biomedical research. We present
      a range of potential factors contributing to these differences in recruitment
      rates, which we believe are worth considering in future community sensitisation
      plans. We conclude by arguing for carefully designed social science research
      around the implementation and impact of community sensitisation activities. 

PMID- 24030881
TI  - The effects of standardised protocols of obstetric and neonatal care on perinatal
      and early neonatal mortality at a rural hospital in Tanzania.
AB  - The care of pregnant women and neonates in peripheral hospitals in many
      developing countries is in a critical state. Through a retrospective analysis we
      assessed the effects of the introduction of standardised protocols in obstetric
      and neonatal care (implementation from 1998 onwards) on perinatal and neonatal
      outcomes of all deliveries over seven years (1996-2002) at a first-referral
      hospital in rural Tanzania. In all, there were 18 026 deliveries (18 316 live
      births and 606 stillbirths). Perinatal mortality rates (PMR) varied from 42.8
      54.5/1000 live births during the years. Early neonatal mortality rates (eNMR)
      fell from 21.9/1000 live births in 1996 to 14.8/1000 live births in 2002 (all p >
      0.05). Fresh stillbirth rates decreased over time (p = 0.041), however macerated
      stillbirth rates increased during the second half of the period (p = 0.067).
      Sixty-two to seventy-two percent of eNMR occurred on the first day of life (p <
      0.001). Maternal mortality ratio declined from 729/100 000 live births in 1996 to
      119/100 000 live births in 2002 (p = 0.002). Our clinical project was associated
      with a reduction of PMR and eNMR (and maternal mortality ratios), but with
      considerable fluctuations during the years. Improving obstetric and neonatal care
      in the hospital setting in developing countries is essential, but needs long-term
      commitment and support. 

PMID- 24030882
TI  - Acceptability of coitally-associated versus daily use of 1% tenofovir vaginal gel
      among women in Pune, India.
AB  - This study reports on the acceptability of 1% tenofovir microbicide gel among
      participants randomised to the coitally-associated use (n = 50) or daily use (n =
      50) arms of a Phase II clinical trial in Pune, India. In a 6-month follow-up
      study, information on behavioural domains was collected on a 6-point Likert scale
      and gel acceptability was measured on a 5-point Likert scale. Random intercept
      logistic modelling was performed to examine the simultaneous effects of study
      arm, follow-up time, sociodemographic factors and behavioural domains on gel
      acceptability. The mean age of female participants was 32.7 years. Women in both
      study arms had similar sociodemographic profiles. Women liked features such as
      easy use of the gel and its protective effect against HIV. Messiness was the most
      disliked feature. Gel acceptability increased during subsequent follow-up visits
      in both arms, especially in the coitally-associated use arm. Non-acceptability of
      the gel was almost two and a half times higher in daily users (adjusted odds
      ratio 2.55, 95% CI 1.18-5.51; p = 0.017). Acceptability differed significantly
      between the two study arms at 2 months (68% vs 40%; p = 0.006) and 6 months (64%
      vs 46%; p = 0.07). Acceptability was significantly lower in those participants
      who reported 'messiness' as the most disliked feature (odds ratio 2.42, 95% CI
      1.02-5.72; p = 0.045). In conclusion, microbicides were more acceptable in
      coitally-associated users than in daily users. Leakage was a problem that
      requires attention. Positioning of the product in a setting such as India where
      the majority of decision-making is done by men would need extensive and
      systematic education of men. 

PMID- 24030883
TI  - The role of private health facilities in the provision of malaria case management
      and prevention services in four zones of Oromia Regional State, Ethiopia.
AB  - Little is known about the contribution of the private health sector in managing
      malaria cases and contributing to malaria prevention and control efforts in
      Ethiopia. We assessed 102 private health facilities and 92 drug outlets in 20
      districts of Oromia Regional State, Ethiopia, for their provision of malaria
      specific services. Of the assessed health facilities 86% provided such services.
      Diagnosis was largely clinical, with only 31% and 15% of all health facilities
      seen using rapid diagnostic tests and microscopy, respectively. Facilities had
      chloroquine, artemether-lumefantrine, quinine and sulfadoxine-pyremethamine. Gaps
      were seen in provision of guidelines and other malaria-related materials,
      training of facility staff and supervision. Inclusion of the private health
      sector in malaria control program is crucial to expand current malaria prevention
      and control efforts in Ethiopia. 

PMID- 24030884
TI  - Evaluation of scaling-up should take into account financial access: Comment on:
      Evaluating the scale-up for maternal and child survival: a common framework.

PMID- 24030885
TI  - Maladaptive dependency schemas, posttraumatic stress hyperarousal symptoms, and
      intimate partner aggression perpetration.
AB  - This study examined the associations between maladaptive dependency-related
      schemas, posttraumatic stress disorder (PTSD) hyperarousal symptoms, and intimate
      partner psychological and physical aggression in a sample of court-referred men
      (N = 174) participating in a domestic-abuser-intervention program. The men were
      largely African American; average age was 33.5 years. The extent to which
      hyperarousal symptoms moderated the association between dependency schemas and
      aggression was also examined. Maladaptive dependency-related schemas were
      positively associated with severe psychological, and mild and severe physical
      aggression perpetration. Hyperarousal symptoms were positively associated with
      mild and severe psychological aggression, and mild physical aggression
      perpetration. Multiple regression analyses showed a significant interaction for
      mild physical aggression: For those with high levels of hyperarousal symptoms,
      greater endorsement of maladaptive dependency schemas was associated with the
      perpetration of aggression (B = 0.98, p = .001). For those with low levels of
      hyperarousal symptoms, there was no association between dependency schemas and
      aggression (B = 0.04, ns). These findings suggest that focusing on problematic
      dependency and PTSD-hyperarousal symptoms in domestic-abuser-intervention
      programs may be helpful, and that examining related variables as possible
      moderators between dependency schemas and intimate aggression would be a fruitful
      area for future research.

PMID- 24030886
TI  - Preparation and physicochemical characterization of acyclovir cocrystals with
      improved dissolution properties.
AB  - Acyclovir is a well-known antiviral agent. It can be administered in very high
      doses (from 200 to 1000 mg even three-four times daily). It has absorption
      problems mainly due to its poor solubility in water (about 0.2 g/100 mL at 25
      degrees C) and its oral bioavailability is approximately 15%-20% with a half-life
      of about 3 h. To improve acyclovir solubility and/or its dissolution properties,
      two cocrystals of this drug were successfully produced with glutaric acid
      (AGA1:1) and fumaric acid (AFA1:1) as conformers, using a cogrinding method.
      Their effective formation was investigated by a broad range of techniques:
      thermal analysis, Fourier transform infrared spectroscopy, X-ray powder
      diffraction, solid state nuclear magnetic resonance, and scanning electron
      microscopy coupled with energy dispersive X-ray spectrometry. The water
      solubility of the AGA1:1 cocrystal was not improved in comparison to acyclovir,
      while AFA1:1 showed a slight increased solubility at equilibrium. The main
      difference was detected in terms of intrinsic dissolution rates (IDR). The IDR of
      the new phases were much faster compared with acyclovir, particularly at neutral
      pH. AFA1:1 showed the most rapid dissolution behavior in water; within 10 min,
      the drug was released completely, while just 60% of acyclovir was dissolved in 1
      h.

PMID- 24030887
TI  - Force sensing of multiple-DOF cable-driven instruments for minimally invasive
      robotic surgery.
AB  - BACKGROUND: Force sensing for robotic surgery is limited by the size of the
      instrument, friction and sterilization requirements. This paper presents a force
      sensing instrument to avoid these restrictions. METHODS: Operating forces were
      calculated according to cable tension. Mathematical models of the force-sensing
      system were established. A force-sensing instrument was designed and fabricated.
      A signal collection and processing system was constructed. RESULTS: The presented
      approach can avoid the constraints of space limits, sterilization requirements
      and friction introduced by the transmission parts behind the instrument wrist.
      Test results showed that the developed instrument has a 0.03 N signal noise, a
      0.05 N drift, a 0.04 N resolution and a maximum error of 0.4 N. The validation
      experiment indicated that the operating and grasping forces can be effectively
      sensed. CONCLUSIONS: The developed force-sensing system can be used in minimally
      invasive robotic surgery to construct a force-feedback system.

PMID- 24030888
TI  - Contact with primary care: the experience of people with intellectual
      disabilities.
AB  - BACKGROUND: People with intellectual disabilities experience disparities in their
      health and health care. Annual health checks are intended to counter such
      disparity by improving access to primary health care. However, little is known
      about their experience of having a health check or other types of contact with
      primary care services. MATERIALS AND METHODS: The findings of two studies which
      used focus groups were combined. 102 people with intellectual disabilities
      participated in the focus groups. RESULTS: Participants' experiences of primary
      care services generally, and health checks in particular, were positive. However,
      unanimity was rare on any of the topics discussed and a number of areas of
      dissatisfaction emerged. CONCLUSIONS: Further studies with larger and more
      representative samples are necessary as feedback from people with intellectual
      disabilities about their experience of contact with primary care staff might help
      to enhance GP knowledge about their health requirements.

PMID- 24030889
TI  - Authors' redress on 'robustness of methods for blinded sample size re-estimation
      with overdispersed count data'.

PMID- 24030891
TI  - Tandem LC columns for the simultaneous retention of polar and nonpolar molecules
      in comprehensive metabolomics analysis.
AB  - The tandem use of hydrophilic interaction LC columns with RP columns in series
      configuration has resulted in the retention of both polar and nonpolar components
      in complex biological samples (mouse serum) in a single analysis. This approach
      successfully coupled various columns with orthogonal separation characteristics,
      employed a single solvent gradient program compatible with the two columns and
      used ESI coupled to a TOF mass spectrometer for detection. Ion suppression, a
      common problem in ESI, was virtually eliminated for components eluting with
      apparent capacity factors >0.7. Retention time reproducibility with the tandem
      columns performed over three days with over 100 injections was comparable to that
      observed for single columns alone. This method was applied to the analysis of a
      pooled mouse serum sample and afforded highly reproducible data for up to 3000
      mass spectral features. This approach was implemented with a conventional LC-MS
      system and should find broad applicability in the comprehensive analysis of
      complex mixtures containing a wide range of compound polarities. 

PMID- 24030890
TI  - Pro-inflammatory macrophages increase in skeletal muscle of high fat-fed mice and
      correlate with metabolic risk markers in humans.
AB  - OBJECTIVE: In obesity, immune cells infiltrate adipose tissue. Skeletal muscle is
      the major tissue of insulin-dependent glucose disposal, and indices of muscle
      inflammation arise during obesity, but whether and which immune cells increase in
      muscle remain unclear. METHODS: Immune cell presence in quadriceps muscle of wild
      type mice fed high-fat diet (HFD) was studied for 3 days to 10 weeks, in CCL2-KO
      mice fed HFD for 1 week, and in human muscle. Leukocyte presence was assessed by
      gene expression of lineage markers, cyto/chemokines and receptors;
      immunohistochemistry; and flow cytometry. RESULTS: After 1 week HFD,
      concomitantly with glucose intolerance, muscle gene expression of Ly6b, Emr1
      (F4/80), Tnf, Ccl2, and Ccr2 rose, as did pro- and anti-inflammatory markers
      Itgax (CD11c) and Mgl2. CD11c+ proinflammatory macrophages in muscle increased by
      76%. After 10 weeks HFD, macrophages in muscle increased by 47%. Quadriceps from
      CCL2-KO mice on HFD did not gain macrophages and maintained insulin sensitivity.
      Muscle of obese, glucose-intolerant humans showed elevated CD68 (macrophage
      marker) and ITGAX, correlating with poor glucose disposal and adiposity.
      CONCLUSION: Mouse and human skeletal muscles gain a distinct population of
      inflammatory macrophages upon HFD or obesity, linked to insulin resistance in
      humans and CCL2 availability in mice.

PMID- 24030892
TI  - Dense arrays of highly aligned graphene nanoribbons produced by substrate
      controlled metal-assisted etching of graphene.
AB  - Dense arrays of aligned graphene nanoribbons (GNRs) are fabricated by substrate
      controlled etching of large-area single-layer graphene. An adequate choice of
      etching substrate and catalyst deposition method allows densities up to 25
      nanoribbons MUm(-1) to be obtained with average widths of 19 nm. The efficacy of
      the method is evidenced by the high on/off ratios of back-gated transistors made
      with these GNRs, which can go up to 5000. 

PMID- 24030894
TI  - Probes, sensors, and labels: why is real progress slow?

PMID- 24030893
TI  - Computer-aided parachute guiding system for closed reduction of diaphyseal
      fractures.
AB  - BACKGROUND: Closed reduction is of great benefit for fracture healing. However,
      achieving this without sacrificing the reduction accuracy and exposing the
      surgeon and patient to excessive radiation is difficult. METHODS: A novel
      parachute guiding system (ParaEx System) was developed for closed reduction of
      fractures based on computed tomography data. The system included two counter
      guides with stainless tubular markers that could be attached to the unilateral
      external fixator. Comminuted tibial diaphyseal fracture models were used to
      validate the ParaEx System. RESULTS: The mean errors (and standard deviations) of
      residual rotational and translational deformity were 0.67 degrees  +/- 0.45
      degrees , 0.92 degrees  +/- 1.00 degrees , and 0.64 degrees  +/- 0.50 degrees  in
      rotation and 1.30 +/- 1.10 mm, 1.13 +/- 0.70 mm, and 0.94 +/- 0.92 mm in
      translation about the X, Y, and Z axes of the local coordinate axes,
      respectively. CONCLUSIONS: The ParaEx System was useful for accurate closed
      reduction of fractures at low cost.

PMID- 24030896
TI  - Self-assembly of Au15 into single-cluster-thick sheets at the interface of two
      miscible high-boiling solvents.
AB  - Wet (nano)blanket: The self-assembly of Au nanoclusters into single-cluster-thick
      nanosheets is performed in two miscible high-boiling solvents with a slight
      polarity difference, which generates microphase separation and acts as a soft
      template to direct the self-assembly in a two-dimensional orientation. 

PMID- 24030897
TI  - A synthetic riboswitch that operates using a rationally designed ligand-RNA pair.
AB  - The construction of an artificial riboswitch is based on a ligand-RNA pair
      without any molecular biology-based selection processes. The ligand selectively
      and significantly stabilized an RNA duplex containing an r(XGG)/r(XGG) sequence
      (X=U, A, G). The integration of the ligand-binding sequences into the 5'
      untranslated region of mRNA provided an artificial riboswitch that was responsive
      to Z-NCTS. 

PMID- 24030898
TI  - Steering target selectivity and potency by fragment-based de novo drug design.
AB  - Kinase inhibitors: Ligand-based de novo design is validated as a viable
      technology for rapidly generating innovative compounds possessing the desired
      biochemical profile. The study discloses the discovery of the most selective
      vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor (right
      in scheme) known to date as prime lead for antiangiogenic drug development.

PMID- 24030899
TI  - Dynamic prediction of risk of death using history of cancer recurrences in joint
      frailty models.
AB  - Evaluating the prognosis of patients according to their demographic, biological,
      or disease characteristics is a major issue, as it may be used for guiding
      treatment decisions. In cancer studies, typically, more than one endpoint can be
      observed before death. Patients may undergo several types of events, such as
      local recurrences and distant metastases, with death as the terminal event.
      Accuracy of clinical decisions may be improved when the history of these
      different events is considered. Thus, it may be useful to dynamically predict
      patients' risk of death using recurrence history. As previously applied within
      the framework of joint models for longitudinal and time to event data, we propose
      a dynamic prediction tool based on joint frailty models. Joint modeling accounts
      for the dependence between recurrent events and death, by the introduction of a
      random effect shared by the two processes. We estimate the probability of death
      between the prediction time t and a horizon t + w, conditional on information
      available at time t. Prediction can be updated with the occurrence of a new
      event. We proposed and compared three prediction settings, taking into account
      three different information levels. The proposed tools are applied to patients
      diagnosed with a primary invasive breast cancer and treated with breast
      conserving surgery, followed for more than 10 years in a French comprehensive
      cancer center.

PMID- 24030900
TI  - Functional analysis of a point mutation in the ryanodine receptor of Plutella
      xylostella (L.) associated with resistance to chlorantraniliprole.
AB  - BACKGROUND: The diamondback moth, Plutella xylostella (L.) has developed
      extremely high resistance to chlorantraniliprole and other diamide insecticides
      in the field. A glycine to glutamic acid substitution (G4946E) in the P.
      xylostella ryanodine receptor (PxRyR) has been found in two resistant populations
      collected in Thailand and Philippines and was considered associated with the
      diamide insecticides resistance but no experimental evidence was provided. The
      present study aimed to clarify the function of the reported mutation in
      chlorantraniliprole resistance in P. xylostella. RESULTS: We identified the same
      mutation (G4946E) in PxRyR from four field collected chlorantraniliprole
      resistant populations of Plutella xylostella in China. Most importantly, we found
      that the frequency of the G4946E mutation is significantly correlated to the
      chlorantraniliprole resistance ratios in P. xylostella (R(2)  = 0.82, P =
      0.0003). Ligand binding assays showed that the binding affinities of the PxRyR to
      the chlorantraniliprole in three field resistant populations were 2.41-, 2.54-
      and 2.60-times lower than that in the susceptible one. CONCLUSION: For the first
      time we experimentally proved that the G4946E mutation in PxRyR confers
      resistance to chlorantraniliprole in Plutella xylostella. These findings pave the
      way for the complete understanding of the mechanisms of diamide insecticides
      resistance in insects.

PMID- 24030901
TI  - Insulin secretion and its association with physical activity, fitness and screen
      time in children.
AB  - OBJECTIVES: To determine the independent associations of moderate to vigorous
      physical activity (MVPA), fitness, screen time, and adiposity with insulin
      secretion in children. DESIGN AND METHODS: Caucasian youth (n = 423/630), 8-10
      years old, with at least one obese biological parent, were studied (QUALITY
      cohort). Insulin secretion was measured using HOMA2-%B, area under the curve
      (AUC) of insulin to glucose over the first 30 minutes (AUC I/G(t30min)) of the
      OGTT and AUC I/G(t120min) over 2 hours. Fitness was measured by VO2peak ; percent
      fat mass (PFM) by DXA; 7-day MVPA by accelerometry; self-reported screen time
      included television, video game, or computer use. Models were adjusted for age,
      sex, season, puberty, PFM, and insulin sensitivity [IS] (HOMA2-IS, Matsuda-ISI).
      RESULTS: PFM was strongly associated with insulin secretion, even after
      adjustment for IS: for every 1% increase in PFM, insulin secretion increased from
      0.3% to 0.8% across indices. MVPA was negatively associated with HOMA2-%B (P <
      0.05), but not with OGTT-derived measures. Fitness was negatively associated with
      AUC I/G(t120min) (P < 0.05). Screen time showed a trend toward higher HOMA2-%B in
      girls (P = 0.060). CONCLUSIONS: In children with an obese parent, lower insulin
      secretion is associated with lower adiposity, higher MVPA, better fitness, and
      possibly reduced screen time.

PMID- 24030902
TI  - Direct observation of quantum-confined graphene-like states and novel hybrid
      states in graphene oxide by transient spectroscopy.
AB  - Quantum-confined graphene-like electronic states are directly observed in
      graphene oxide and photothermally reduced graphene oxide via transient
      spectroscopy. An unexpected novel hybrid state arising from amorphous carbon-like
      peripheral structure with high sp(3) /sp(2) carbon ratio in close vicinity of
      confined graphene-like states is found commonly existent in various carbon
      nanomaterials, including graphene oxide, graphene quantum dots, and carbon dots. 

PMID- 24030903
TI  - Reporting of serious adverse events during cancer clinical trials to the
      institutional review board: an evaluation by the research on adverse drug events
      and reports (RADAR) project.
AB  - Global introspection is considered an unreliable method for attribution of
      causality of serious adverse events (SAEs), yet remains widely used for cancer
      drug clinical trials. Here, we compare structured case abstraction (SCA) to the
      routine method for detecting, evaluating, and reporting ADEs during cancer drug
      clinical trials to an Institutional Review Board (IRB). We obtained all SAE
      reports (2001-2008) received by one IRB for six clinical trials involving
      bevacizumab or oxaliplatin for treatment of gastrointestinal cancers. We compared
      the routine IRB SAE method to SCA for adverse event detection and causality
      attribution. Of 205 adverse events, 182 events (75%) were not reported; of these,
      6 (20%) of 30 SAEs requiring an IRB report were unreported. For the 10 item
      Naranjo score, the amount of information useful for causality attribution was
      higher with SCA than the routine method (6.0 vs. 2.4 items, P < .0001). One-fifth
      of SAEs requiring an IRB report were unreported to the IRB via the routine
      method. SCA provided more useful information as to whether an SAE was caused by a
      cancer drug exposure. Our results suggest that SCA may improve SAE detection and
      the accuracy of attribution of causality during cancer drug clinical trials. 

PMID- 24030904
TI  - Towards virtual FLS: development of a peg transfer simulator.
AB  - BACKGROUND: Peg transfer is one of five tasks in the Fundamentals of Laparoscopic
      Surgery (FLS), program. This paper reports the development and validation of a
      Virtual Basic Laparoscopic Skill Trainer-Peg Transfer (VBLaST-PT((c)) ) simulator
      for automatic real-time scoring and objective quantification of performance.
      METHODS: New techniques have been introduced in order to allow bi-manual
      manipulation of pegs and automatic scoring/evaluation while maintaining high
      quality of simulation. A preliminary face and construct validation study was
      performed with 22 subjects divided into two groups: experts (PGY 4-5, fellow and
      practicing surgeons) and novice (PGY 1-3). RESULTS: Face validation shows high
      scores for all aspects of the simulation. Two-tailed Mann-Whitney U-test scores
      showed significant differences between the two groups on completion time (P =
      0.003), FLS score (P =0.002) and the VBLaST-PT(c) score (P = 0.006). CONCLUSIONS:
      VBLaST-PT((c)) is a high quality virtual simulator that showed both face and
      construct validity.

PMID- 24030905
TI  - On the way towards greener transition-metal-catalyzed processes as quantified by
      E factors.
AB  - Transition-metal-catalyzed carbon-carbon and carbon-heteroatom bond formations
      are among the most heavily used types of reactions in both academic and
      industrial settings. As important as these are to the synthetic community, such
      cross-couplings come with a heavy price to our environment, and sustainability. E
      Factors are one measure of waste created, and organic solvents, by far, are the
      main contributors to the high values associated, in particular, with the
      pharmaceutical and fine-chemical companies which utilize these reactions. An
      alternative to organic solvents in which cross-couplings are run can be found in
      the form of micellar catalysis, wherein nanoparticles composed of newly
      introduced designer surfactants enable the same cross-couplings, albeit in water,
      with most taking place at room temperature. In the absence of an organic solvent
      as the reaction medium, organic waste and hence, E Factors, drop dramatically.

PMID- 24030906
TI  - Electronic nose for tracking different types of leukaemia: future prospects in
      diagnosis.

PMID- 24030907
TI  - Cross-resistance between cyenopyrafen and pyridaben in the twospotted spider mite
      Tetranychus urticae (Acari: Tetranychidae).
AB  - BACKGROUND: Cyenopyrafen is an inhibitor of complex II of the mitochondrial
      electron transport chain. It has a molecular structure that shares some common
      features with frequently used complex I inhibitors such as pyridaben. To evaluate
      whether this similarity in structure poses a cross-resistance risk that might
      complicate resistance management, we selected for pyridaben and cyenopyrafen
      resistance in the laboratory and characterized resistance. RESULTS: The selection
      for cyenopyrafen conferred cross-resistance to pyridaben and vice versa.
      Resistance towards these both acaricides was incompletely dominant in adult
      females. However, in eggs maternal effects were observed in pyridaben resistance,
      but not in the cyenopyrafen-resistance (completely dominant). In the cyenopyrafen
      resistant strain, the LC50 of eggs remained lower than the commercially
      recommended concentration. The common detoxification mechanisms by cytochrome
      P450 was involved in resistance to these acaricides. Carboxyl esterases were also
      involved in cyenopyrafen resistance as a major factor. CONCLUSIONS: Although
      cross-resistance suggests that pyridaben resistance would confer cyenopyrafen
      cross-resistance, susceptibility in eggs functions to delay the development of
      cyenopyrafen resistance.

PMID- 24030909
TI  - Wide-range temperature sensing using highly sensitive green-luminescent ZnO and
      PMMA-ZnO film as a non-contact optical probe.
AB  - The heat is on: A variation of green luminescence intensity of ZnO microcrystals
      embedded in poly(methyl methacrylate) is observed. This material is used for non
      contact thermometer, which has an accuracy of 0.1 K over a temperature range of
      83-474 K. Scale bars: 10 MUm. 

PMID- 24030910
TI  - Learning curve and early clinical outcomes for a robotic surgery novice
      performing robotic single site cholecystectomy.
AB  - BACKGROUND: A rapid training protocol has been developed for robotic surgery
      novices to learn robotic single-incision techniques. This study assesses the
      learning curve and early clinical results for a robotic surgery novice starting
      single-site cholecystectomy. METHODS: A chart review was performed on the
      surgeon's first 55 patients to undergo this procedure. RESULTS: Average patient
      age was 46.01 +/- 4.25 (range 21-86) years and BMI was 26.57 +/- 4.25 (range 19.4
      36.6) kg/m(2) . The mean port placement with docking time was 11.34 +/- 3.74
      (range 7-23) min. Mean console time was 28.74 +/- 11.04 (range 15-66) min.
      Average total OR time was 61.84 +/- 14.66 (range 40-105) min. All procedures were
      successfully completed without conversion or added ports. Complications included
      several minor procedural gall bladder perforations and miscellaneous
      postoperative symptomatic complaints. CONCLUSION: Robotic single site
      cholecystectomy can be safely performed by a robotic novice within a minimal
      learning curve and have early clinical results that are comparable to the
      published data of robotic experts.

PMID- 24030911
TI  - Best practices in family-centered early intervention for children who are deaf or
      hard of hearing: an international consensus statement.
AB  - A diverse panel of experts convened in Bad Ischl, Austria, in June of 2012 for
      the purpose of coming to consensus on essential principles that guide family
      centered early intervention with children who are deaf or hard of hearing (D/HH).
      The consensus panel included parents, deaf professionals, early intervention
      program leaders, early intervention specialists, and researchers from 10 nations.
      All participants had expertise in working with families of children who are D/HH,
      and focus was placed on identifying family-centered practice principles that are
      specific to partnering with these families. Panel members reported that the
      implementation of family-centered principles was uneven or inconsistent in their
      respective nations. During the consensus meeting, they identified 10 agreed-upon
      foundational principles. Following the conference, they worked to refine the
      principles and to develop a document that described the principles themselves,
      related program and provider behaviors, and evidence supporting their use
      (drawing upon studies from multiple disciplines and nations). The goal of this
      effort was to promote widespread implementation of validated, evidence-based
      principles for family-centered early intervention with children who are deaf and
      hard of hearing and their families. 

PMID- 24030916
TI  - Electrically pumped mid-infrared random lasers.
AB  - Electrically pumped random lasers, operating in the mid-infrared regime at lambda
      ~ 10 MUm, are realized for the first time. Randomly distributed air holes are
      patterned onto a quantum cascade wafer emitting in the transverse-magnetic (TM)
      polarization. The advantage of employing TM polarized gain medium is that TM
      modes are more effectively confined in the gain region, and thus improve lasing
      efficiency and vertical confinement compared to TE modes. 

PMID- 24030917
TI  - Pharmacokinetics of tofacitinib, a janus kinase inhibitor, in patients with
      impaired renal function and end-stage renal disease.
AB  - The pharmacokinetics (PK) of tofacitinib were assessed in patients with mild
      (Cockcroft-Gault creatinine clearance >50 and <=80 mL/min), moderate (>=30 and
      <=50 mL/min), and severe (<30 mL/min) renal impairment, and end-stage renal
      disease (ESRD) requiring dialysis. Six patients each with normal, mild, moderate,
      or severely impaired renal function, and 12 patients with ESRD, received single
      tofacitinib doses of 10 mg. PK data were obtained from blood and dialyzate
      (patients with ESRD only) samples prior and subsequent to dosing and/or
      hemodialysis (patients with ESRD only). Relative to patients with normal renal
      function, mean (90% CI) AUC(0-infinity) ratios were 137% (97-195), 143% (101
      202), and 223% (157-316) in patients with mild, moderate, and severe renal
      impairment, respectively. Maximum plasma concentrations (Cmax ) were similar
      across the four treatment groups. Terminal phase half-life (t1/2 ) increased with
      severity of renal impairment. Mean AUC(0-infinity) in patients with ESRD on a non
      dialysis day was similar to that in patients with moderate renal impairment and
      approximately 40% greater than healthy volunteer data. Mean (SD) dialyzer
      efficiency (ratio of dialyzer clearance/blood flow entering the dialyzer) was
      0.73 (0.15). However, due to extensive non-renal clearance, dialysis procedure is
      unlikely to result in significant elimination of tofacitinib.

PMID- 24030919
TI  - Efficient construction of pyrano[3,2-a]carbazoles: application to a biomimetic
      total synthesis of cyclized monoterpenoid pyrano[3,2-a]carbazole alkaloids.
AB  - We have developed a highly efficient route to 2-hydroxy-3-methylcarbazole (1) via
      a palladium-catalyzed construction of the carbazole skeleton. Using 1 as relay
      compound, different methods for annulations of pyran rings by reaction with
      terpenoid building blocks have been tested. The Lewis acid promoted reaction of 1
      with prenal (21) opened up an efficient route to girinimbine (3) and the
      corresponding reaction with citral (25) afforded mahanimbine (5). Oxidation of
      compounds 3 and 5 provided murrayacine (4) and murrayacinine (6). Following the
      biogenetic proposal, mahanimbine (5) has been exploited for efficient biomimetic
      syntheses of the cyclized monoterpenoid pyrano[3,2-a]carbazole alkaloids
      cyclomahanimbine (7), mahanimbidine (8) and bicyclomahanimbine (9). The
      interconversions of 5, 7, 8 and 9 are described and mechanistic implications are
      discussed. Structural assignments are unambiguously verified by X-ray crystal
      structure determinations. Moreover, cyclomahanimbine (7) was transformed into
      murrayazolinine (10) and exozoline (11). 

PMID- 24030918
TI  - Phase II study of pegylated liposomal doxorubicin, low-dose dexamethasone, and
      lenalidomide in patients with newly diagnosed multiple myeloma.
AB  - Our previous phase I/II trial of pegylated liposomal doxorubicin (PLD), low-dose
      dexamethasone, and lenalidomide in patients with relapsed and refractory myeloma
      showed an overall response rate of 75%, with 29% achieving >= VGPR. Here, we
      investigated this combination (PLD 30 or 40 mg/m(2) intravenously, day 1;
      dexamethasone 40 mg orally, days 1-4; lenalidomide 25 mg orally, days 1-21;
      administered every 28 days) in a phase II study in patients with newly diagnosed
      symptomatic multiple myeloma to determine its efficacy and tolerability
      (ClinicalTrials.gov NCT00617591). At best response, patients could proceed with
      high-dose melphalan or with maintenance lenalidomide and dexamethasone. In 57
      patients, we found that the overall response rate and rate of very good partial
      response and better on intent-to-treat, our primary endpoints, were 77.2% and
      42.1%, respectively, with responses per the International Myeloma Working Group.
      Median progression-free survival was 28 months (95% CI 18.1-34.8), with 1- and 2
      year overall survival rates of 98.1 and 79.6%. During induction, grade 3/4
      toxicities were neutropenia (49.1%), anemia (15.8%), thrombocytopenia (7%),
      fatigue (14%), febrile neutropenia (8.8%), and venous thromboembolic events
      (8.8%). During maintenance, grade 3/4 toxicities were mainly hematologic. We
      found this combination to be active in patients with newly diagnosed myeloma,
      with results comparable to other lenalidomide-based induction strategies without
      proteasome inhibition. In addition, maintenance therapy with lenalidomide was
      well tolerated.

PMID- 24030920
TI  - The incidence of mild and severe hypoglycaemia in patients with type 2 diabetes
      mellitus treated with sulfonylureas: a systematic review and meta-analysis.
AB  - Patients with type 2 diabetes mellitus using sulfonylurea derivatives or insulin
      may experience hypoglycaemia. However, recent data regarding the incidence of
      hypoglycaemia are scarce. We conducted a systematic review and meta-analysis to
      determine the proportion of patients with type 2 diabetes mellitus that
      experience hypoglycaemia when treated with sulfonylurea or insulin. We searched
      MEDLINE and EMBASE for randomized controlled trials that compared incretin-based
      drugs to sulfonylureas or insulin and assessed hypoglycaemia incidence in the
      latter therapies. Subgroup and meta-regression analyses were performed to study
      possible associations with potential risk factors for hypoglycaemia. Data of 25
      studies were extracted, 22 for sulfonylurea and 3 for insulin. Hypoglycaemia with
      glucose <=3.1 mmol/L or <=2.8 mmol/L was experienced by 10.1% [95% confidence
      interval (CI) 7.3-13.8%] and 5.9% (95% CI 2.5-13.4%) of patients with any
      sulfonylurea treatment. Severe hypoglycaemia was experienced by 0.8% (95% CI 0.5
      1.3%) of patients. Hypoglycaemia with glucose <=3.1 mmol/L and severe
      hypoglycaemia occurred least frequently with gliclazide: in 1.4% (95% CI 0.8
      2.4%) and 0.1% (95% CI 0-0.7%) of patients, respectively. None of the risk
      factors were significant in a stepwise multivariate meta-regression analysis. Too
      few studies had insulin as comparator, so these data could not be meta-analysed.
      The majority of patients with type 2 diabetes mellitus on sulfonylurea therapy in
      clinical trials remain free of any relevant hypoglycaemia. Gliclazide was
      associated with the lowest risk of hypoglycaemia. Because participants in
      randomized controlled trials differ from the general population, care should be
      taken when translating these data into clinical practice.

PMID- 24030921
TI  - Active cross-linkers that lead to active gels.
AB  - Chemomechanical reaction: The first octahedral ruthenium bipyridine complex that
      bears six polymerizable vinyl groups is used as an active cross-linker. It is a
      key building block for cross-linked polymeric networks (right) thus allowing the
      construction of molecular architectures in chemomechanical soft materials. 

PMID- 24030922
TI  - 2D DIGE based proteomics study of erythrocyte cytosol in sickle cell disease:
      altered proteostasis and oxidative stress.
AB  - Sickle cell disease (SCD) is a hemolytic disorder caused by a mutation in beta
      globin gene and affects millions of people worldwide. Though clinical
      manifestations of the disease are quite heterogeneous, many of them occur due to
      erythrocyte sickling at reduced oxygen concentration and vascular occlusion
      mediated via blood cell adhesion to the vessel wall. We have followed proteomic
      approach to resolve the differentially regulated proteins of erythrocyte cytosol.
      The deregulated proteins mainly fall in the group of chaperone proteins such as
      heat shock protein 70, alpha hemoglobin stabilizing protein, and redox regulators
      such as aldehyde dehydrogenase and peroxiredoxin-2 proteoforms. Proteasomal
      subunits are found to be upregulated and phospho-catalase level also got altered.
      Severe oxidative stress inside erythrocyte is evident from the ROS analysis and
      Oxyblot(TM) experiments. Peroxiredoxin-2 shows significant dimerization in the
      SCD patients, a hallmark of oxidative stress inside erythrocytes. One interesting
      fact is that most of the differentially regulated proteins are also common for
      hemoglobinopathies such as Ebeta thalassemia. These could provide important clues
      in understanding the pathophysiology of SCD and lead us to better patient
      management in the future. 

PMID- 24030923
TI  - Obesity impairs vasodilatation and blood flow increase mediated by endothelial
      nitric oxide: an overview.
AB  - Obesity dramatically increases the risk of development of cardiovascular and
      metabolic diseases. Endothelial dysfunction induced by obesity is an important
      risk factor that impairs blood flow controls in various organs. Impaired
      endothelial function occurs early in life in obese children. Obesity-induced
      endothelial dysfunction is associated with decreased nitric oxide (NO) production
      due to impaired endothelial NO synthase activity and expression and increased
      production of superoxide anion and the endogenous NOS inhibitor ADMA, together
      with increased vasoconstrictor factors, such as endothelin-1 and sympathetic
      nerve activation. Decreased endothelial progenitor cells are also involved in
      endothelial cell senescence in obese individuals. Insulin resistance and diabetes
      mellitus augment obesity-induced endothelial dysfunction. Adipokines liberated
      from adipose tissues play roles in modulating endothelial function; adiponectin
      and ghrelin have beneficial effects on endothelial cells. Effects of leptin on
      endothelial function are controversial. Decreased body weight by physical
      exercise, dietary interventions, and bariatric surgery are effective measures
      that reverse endothelial dysfunction; however, the weight control is not only the
      reason for improving of endothelia function. Pharmacological therapies with beta
      adrenoceptor antagonists, resveratolol, anti-obesity agents, nifedipine, and
      NADPH oxidase inhibitors may also be effective; however, these treatments have to
      be utilized under the basis of exercise and dietary controls. 

PMID- 24030924
TI  - Rapid and extensive collapse from electrically responsive macroporous hydrogels.
AB  - Electrically responsive hydrogels are created with interconnected macropores,
      which greatly enhance their ability to rapidly undergo volumetric collapse when
      subjected to moderate electric fields. When optimized, these electrogels are
      easily integrated into arrays capable of rapid configurational and chromatic
      optical modulations, and when loaded with drugs, are able to coordinate the
      delivery profile of multiple drugs. 

PMID- 24030925
TI  - Spontaneous formation of nitrarine and polycyclic skeletons related to Nitraria
      indolic alkaloids under non-enzymic conditions.
AB  - Mixtures of tryptamine and reactive C5 units, presumably derived from lysine in
      nature, were studied to ascertain the spontaneous formation of the complex
      polycyclic alkaloid nitrarine. Several indolic compounds tracing the unified
      metabolism within the Nitraria genus were also characterized. 

PMID- 24030926
TI  - Vitronectin--master controller or micromanager?
AB  - The concept that the mammalian glycoprotein vitronectin acts as a biological
      'glue' and key controller of mammalian tissue repair and remodelling activity is
      emerging from nearly 50 years of experimental in vitro and in vivo data.
      Unexpectedly, the vitronectin-knockout (VN-KO) mouse was found to be viable and
      to have largely normal phenotype. However, diligent observation revealed that the
      VN-KO animal exhibits delayed coagulation and poor wound healing. This is
      interpreted to indicate that VN occupies a role in the earliest events of
      thrombogenesis and tissue repair. VN is the foundation upon which the thrombus
      grows in an organised structure. In addition to sealing the wound, the thrombus
      also serves to protect the underlying tissue from oxidation, is a reservoir of
      mitogens and tissue repair mediators, and provides a provisional scaffold for the
      repairing tissue. In the absence of VN (e.g., VN-KO animal), this cascade is
      disrupted before it begins. A wide variety of biologically active species
      associate with VN. Although initial studies were focused on mitogens, other
      classes of bioactives (e.g., glycosaminoglycans and metalloproteinases) are now
      also known to specifically interact with VN. Although some interactions are
      transient, others are long-lived and often result in multi-protein complexes.
      Multi-protein complexes provide several advantages: prolonging molecular
      interactions, sustaining local concentrations, facilitating co-stimulation of
      cell surface receptors and thereby enhancing cellular/biological responses. We
      contend that these, or equivalent, multi-protein complexes facilitate VN
      polyfunctionality in vivo. It is also likely that many of the species
      demonstrated to associate with VN in vitro, also associate with VN in vivo in
      similar multi-protein complexes. Thus, the predominant biological function of VN
      is that of a master controller of the extracellular environment; informing, and
      possibly instructing cells 'where' to behave, 'when' to behave and 'how' to
      behave (i.e., appropriately for the current circumstance).

PMID- 24030927
TI  - Imatinib-associated melanosis of the palate.

PMID- 24030929
TI  - Sanfilippo syndrome, glucose-6-phosphate dehydrogenase deficiency and sickle
      cell/beta+ thalassemia in a child: the burden of consanguinity.

PMID- 24030928
TI  - Changes in clearance, volume and bioavailability of immunosuppressants when given
      with HAART in HIV-1 infected liver and kidney transplant recipients.
AB  - Solid organ transplantation in human immunodeficiency virus 1 (HIV)-infected
      individuals requiring the concomitant use of immunosuppressants (IS) [e.g.
      cyclosporine (CsA) or tacrolimus (TAC)] and antiretrovirals (ARVs) [e.g. protease
      inhibitors (PIs) and/or non-nucleoside reverse transcriptase inhibitors (NNRTIs)]
      is complicated by significant drug interactions. This paper describes the
      pharmacokinetics of CsA and TAC in 52 patients on both IS and NNRTIs, PIs or
      combined NNRTIs + PIs, in studies conducted at 2 weeks, 3, 6, 12 and 24 months
      after transplantation. Cyclosporine and TAC blood concentrations were measured by
      LC/MS/MS. This multisubject, varied ARV-IS drug combination, longitudinal
      observational patient study provided a unique opportunity to examine the effect
      of different ARV drugs on IS pharmacokinetics (PK) by comparing the ratios of
      parameters over time and between PK parameters. Subjects taking concomitant PIs
      exhibited increases in CsA and TAC exposure (AUC/dose) due to the increased
      apparent oral bioavailability and decreased apparent oral clearance. Those
      subjects taking CsA and concomitant efavirenz (EFV) showed time dependent
      increases in exposure due to ~30% increases in the apparent oral bioavailability
      over time as well as a decreased apparent oral clearance, while subjects on TAC
      and EFV showed time-dependent changes in all PK parameters. The increased
      bioavailability was not observed in patients on CsA and nevirapine (NVP). These
      differences between IS drugs and the changes in PK parameters are not easily
      predicted, illustrating the importance of continued therapeutic drug monitoring
      in patients on these complex medication regimens. Published 2013. This article is
      a U.S. Government work and is in the public domain in the USA.

PMID- 24030930
TI  - Proteome analysis of functionally differentiated bovine (Bos indicus) mammary
      epithelial cells isolated from milk.
AB  - Mammary gland is made up of a branching network of ducts that end in alveoli.
      Terminally differentiated mammary epithelial cells (MECs) constitute the
      innermost layer of aveoli. They are milk-secreting cuboidal cells that secrete
      milk proteins during lactation. Little is known about the expression profile of
      proteins in the metabolically active MECs during lactation or their functional
      role in the lactation process. In the present investigation, we have reported the
      proteome map of MECs in lactating cows using 2DE MALDI-TOF/TOF MS and 1D-Gel-LC
      MS/MS. MECs were isolated from milk using immunomagnetic beads and confirmed by
      RT-PCR and Western blotting. The 1D-Gel-LC-MS/MS and 2DE-MS/MS based approaches
      led to identification of 431 and 134 proteins, respectively, with a total of 497
      unique proteins. Proteins identified in this study were clustered into functional
      groups using bioinformatics tools. Pathway analysis of the identified proteins
      revealed 28 pathways (p < 0.05) providing evidence for involvement of various
      proteins in lactation function. This study further provides experimental evidence
      for the presence of many proteins that have been predicted in annotated bovine
      genome. The data generated further provide a set of bovine MEC-specific proteins
      that will help the researchers to understand the molecular events taking place
      during lactation. 

PMID- 24030931
TI  - A route for lignin and bio-oil conversion: dehydroxylation of phenols into arenes
      by catalytic tandem reactions.
AB  - Finding a workaround: The conversion of lignin into low-boiling-point arenes
      instead of high-boiling-point phenols could greatly facilitate conventional
      refinery processes. A new procedure for the depolymerization of lignin and
      simultaneous conversion phenols into arenes is described. The method can also be
      rendered as a fundamental finding for the upgrade of bio-oils to arenes under
      mild conditions. 

PMID- 24030932
TI  - Polyelectrolyte multilayer coating of 3D scaffolds enhances tissue growth and
      gene delivery: non-invasive and label-free assessment.
AB  - Layer-by-layer (LbL) deposition is a versatile technique which is beginning to be
      be explored for inductive tissue engineering applications. Here, it is
      demonstrated that a polyelectrolyte multilayer film system composed of glycol
      chitosan (Glyc-CHI) and hyaluronic acid (HA) can be used to coat 3D micro
      fabricated polymeric tissue engineering scaffolds. In order to overcome many of
      the limitations associated with conventional techniques for assessing cell growth
      and viability within 3D scaffolds, two novel, real-time, label-free techniques
      are introduced: impedance monitoring and optical coherence phase microscopy.
      Using these methods, it is shown that LbL-coated scaffolds support in vitro cell
      growth and viability for a period of at least two weeks at levels higher than
      uncoated controls. These polyelectrolyte multilayer coatings are then further
      adapted for non-viral gene delivery applications via incorporation of DNA carrier
      lipoplexes. Scaffold-based delivery of the enhanced green fluorescent protein
      (EGFP) marker gene from these coatings is successfully demonstrated in vitro,
      achieving a two-fold increase in transfection efficiency compared with control
      scaffolds. These results show the great potential of Glyc-CHI/HA polyelectrolyte
      multilayer films for a variety of gene delivery and inductive tissue engineering
      applications. 

PMID- 24030933
TI  - Stereotyped subset #1 chronic lymphocytic leukemia: a direct link between B-cell
      receptor structure, function, and patients' prognosis.
AB  - Chronic lymphocytic leukemia (CLL) with stereotyped B-cell receptor (BCR)
      belonging to subset #1 (IGHV1-5-7/ IGKV1-39) display a poor outcome. To
      characterize their genetic and genomic features and BCR function, we selected 20
      subset #1 CLL from a series of 579 cases. Subset #1 CLL, all showing unmutated
      IGHV, were associated with the presence of del(11q) (50%) in comparison with
      unmutated CLL, unmutated stereotyped CLL other than subset #1 and with cases
      using the same IGHV genes but a heterogeneous VH CDR3 (non-subset #1 CLL). There
      were no distinctive features regarding CD38, ZAP-70, and TP53 disruption. NOTCH1,
      SF3B1, and BIRC3 were mutated in 15%, 0%, and 5% of cases, respectively, while
      BIRC3 was deleted in 22% of cases. Microarray unsupervised analysis on 80
      unmutated/mutated/stereotyped/non-stereotyped CLL showed a tight clustering of
      subset #1 cases. Their genomic signature exhibited several differentially
      expressed transcripts involved in BCR signal transduction, apoptosis regulation,
      cell proliferation, and oxidative processes, regardless of del(11q). Accordingly,
      BCR ligation with anti-IgM revealed a significant higher proliferation of subset
      #1 versus unmutated non-subset #1 CLL, both at baseline and after 24-48 hr
      stimulation. Subset #1 CLL represent a paradigmatic example of the direct link
      between BCR structure, function, and patients prognosis.

PMID- 24030934
TI  - Hybrid assemblies based on a gadolinium-containing polyoxometalate and a cationic
      polymer with spermine side chains for enhanced MRI contrast agents.
AB  - Supramolecular assembly: Spherical and stable hybrid assemblies based on a
      cationic polymer with spermine side chains and an anionic Gd(3+)-containing
      polyoxometalate cluster (GdW) are prepared by electrostatic interaction. The T1
      weighted MRI performance of GdW is enhanced about three times in the assemblies;
      meanwhile, the assemblies show good biocompatibility, which enables them to be
      promising candidates for MRI contrast agents.

PMID- 24030935
TI  - Lengthening our perspective: morphological, cellular, and molecular responses to
      eccentric exercise.
AB  - The response of skeletal muscle to unaccustomed eccentric exercise has been
      studied widely, yet it is incompletely understood. This review is intended to
      provide an up-to-date overview of our understanding of how skeletal muscle
      responds to eccentric actions, with particular emphasis on the underlying
      molecular and cellular mechanisms of damage and recovery. This review begins by
      addressing the question of whether eccentric actions result in physical damage to
      muscle fibers and/or connective tissue. We next review the symptomatic
      manifestations of eccentric exercise (i.e., indirect damage markers, such as
      delayed onset muscle soreness), with emphasis on their relatively poorly
      understood molecular underpinnings. We then highlight factors that potentially
      modify the muscle damage response following eccentric exercise. Finally, we
      explore the utility of using eccentric training to improve muscle function in
      populations of healthy and aging individuals, as well as those living with
      neuromuscular disorders.

PMID- 24030936
TI  - Opioid non-IgE mediated effects in a BAT assay on drug hypersensitivity to
      pholcodine.

PMID- 24030937
TI  - Paracetamol, aspirin, and indomethacin induce endocrine disturbances in the human
      fetal testis capable of interfering with testicular descent.
AB  - CONTEXT: Masculinization depends on the fetal testis. Exposure of the human fetus
      during pregnancy to paracetamol and/or to other mild analgesics is associated
      with an increased risk of cryptorchidism. OBJECTIVE: We aimed to determine
      whether mild analgesics disrupted the morphology and endocrine function of the
      human testis. DESIGN: We used an in vitro system based on the culture of human
      fetal testes exposed or not to paracetamol, its metabolite N-(4-hydroxyphenyl)
      arachidonoylethanolamide (AM404), aspirin, indomethacin, and ketoconazole at 10(
      4) to 10(-7) M. SETTING: The study was conducted at the University of Rennes I.
      PATIENTS/PARTICIPANTS: Human fetal testes were from pregnant women after induced
      abortion, between 7 and 12 weeks of gestation (GW). MAIN OUTCOME MEASURES:
      Testosterone (RIA), anti-Mullerian hormone (ELISA), insulin-like factor 3 (RIA),
      and prostaglandin (PG) D2 and PGE2 (ELISA) were assayed in the medium. Testicular
      cells were counted using histology and image analysis. The possible nuclear
      receptor-mediated activities of the analgesics were investigated using reporter
      cell lines expressing estrogen, androgen, and peroxisome proliferator-activated
      gamma receptors. RESULTS: Indomethacin and aspirin stimulated testosterone
      production, particularly by the younger testes (8-9 GW vs 10-12 GW). Paracetamol,
      AM404, and ketoconazole decreased insulin-like factor 3 levels. Aspirin
      stimulated whereas ketoconazole inhibited AMH production. PGE2 levels were
      inhibited by paracetamol and aspirin in the 7 to 12 GW testes and by indomethacin
      but only in 7 to 9.86 GW testes. The inhibitory trends seen for PGD2 were not
      statistically significant. CONCLUSIONS: Analgesics at concentrations relevant to
      human exposure cause endocrine disturbances in the fetal testis. We suggest that
      the fetal human testis displays slight critical age windows for sensitivity to
      direct exposure to aspirin, indomethacin, and paracetamol. The analgesic-induced
      inhibition of INSL3 may be the mechanism by which analgesics increase the risk of
      cryptorchidism. Greater caution is required concerning consumption of analgesics
      during pregnancy.

PMID- 24030938
TI  - Sinonasal paraganglioma with long-delayed recurrence and metastases: genetic and
      imaging findings.
AB  - CONTEXT: Sinonasal paragangliomas have rarely been reported in the literature.
      They are often aggressive. PATIENT: We report an original case of sinonasal
      paragangliomas with a tumor recurrence diagnosed 13 years after resection of the
      primary tumor. Somatostatin receptor scintigraphy and [18F]-fluorodeoxyglucose
      positron emission tomography/computed tomography were the most sensitive
      functional imaging techniques, and they ruled out distant metastases.
      Interestingly, [18F]-fluorodihydroxyphenylalanine positron emission
      tomography/computed tomography was negative, a feature that may be considered a
      sign of functional dedifferentiation. Screening for germline mutations of the
      SDHB, SDHC, SDHD, SDHAF2, VHL, MAX, and TMEM127 was negative. CONCLUSION: The
      diagnosis of malignancy remains challenging at initial diagnosis, and patients
      should be followed during their entire lifetime.

PMID- 24030939
TI  - Vitamin D3 effects on lipids differ in statin and non-statin-treated humans:
      superiority of free 25-OH D levels in detecting relationships.
AB  - CONTEXT: Inverse associations between 25-OH vitamin D levels and cardiovascular
      morbidity and mortality have been reported. OBJECTIVES: Our goals were to 1)
      investigate effects of correcting inadequate D status on lipids, 2) determine
      whether free 25-OH D is better correlated with lipids than total 25-OH D. DESIGN:
      A randomized, double-blind placebo-controlled trial was performed. SETTING:
      Participants resided in the general community. PARTICIPANTS: Adults with
      inadequate D status were randomized to D3: 14 men, 12 women, age 60 +/- 8 years
      (mean +/- SD) or placebo: 12 men, 11 women: 59 +/-12 years. INTERVENTION:
      Responses to 12-week oral vitamin D3 titrated (1000-3000 IU/d) to achieve 25-OH D
      levels >=25 ng/mL were compared to placebo. MAIN OUTCOME MEASURES: Measurements
      were 25-OH D (tandem mass spectometry), free 25-OH D (direct immunoassay), lipids
      (directly measured triglyceride, cholesterol, and subfractions; plant sterols and
      cholesterol synthesis precursors), and safety labs before and after 6 and 12
      weeks D3 or placebo. Data were analyzed by repeated measures ANOVA and linear
      regression. RESULTS: Vitamin D3 was titrated to 1000 IU/d in 15/26 (58%), to 2000
      IU/d in 10, and 3000 IU/d in one patient. D3 had no effect on cholesterol or
      cholesterol subfractions except for trends for decreases in atorvastatin-treated
      patients (cholesterol, P = .08; low-density lipoprotein [LDL] cholesterol, P =
      .05). Decreased campesterol concentrations (P = .05) were seen with D3 but not
      placebo in statin-treated patients. Relationships between total 25-OH D and
      lipids were not detected, but inverse linear relationships were detected between
      free 25-OH D and triglycerides (P = .03 for all participants [n = 49], P = .03 in
      all statin-treated [n = 19], and P = .0009 in atorvastatin-treated [n = 11]), and
      between free 25-OH D and LDL cholesterol (P = .08 overall, P = .02 in all statin
      treated, and P = .03 for atorvastatin-treated), and total cholesterol (P = .09
      overall; P = .04 for all statin-treated, and P = .05 for atorvastatin-treated).
      CONCLUSIONS: Vitamin D lipid-lowering effects appear limited to statin-treated
      patients and are likely due to decreased cholesterol absorption. Relationships
      between lipids and D metabolites were only detected when free 25-OH D was
      measured, suggesting the superiority of determining free 25-OH D levels compared
      to total 25-OH vitamin D levels when analyzing biologic responses.

PMID- 24030940
TI  - Serum amyloid A: expression throughout human ovarian folliculogenesis and levels
      in follicular fluid of women undergoing controlled ovarian stimulation.
AB  - BACKGROUND: Serum amyloid A (SAA) is an acute phase protein expressed primarily
      in the liver in response to various injuries and inflammatory stimuli and is
      recognized as a modulator of inflammation. Ovarian reproductive functions
      including folliculogenesis and ovulation use inflammatory processes; thus,
      studying SAA in this context is of interest. OBJECTIVES: We investigated the
      expression and localization of SAA in ovarian developing follicles and its levels
      in follicular fluids. METHODS AND PARTICIPANTS: Nonradioactive in situ
      hybridization and immunohistochemical staining were applied on ovarian paraffin
      tissue sections. ELISA and RT-PCR were applied on follicular aspirates and blood
      samples from women undergoing controlled ovarian stimulation for in vitro
      fertilization. RESULTS: Expression of SAA mRNA and protein was found in
      follicular cells at all stages of follicular development, from primordial and
      primary follicles through antral follicles and corpora lutea. Expression was
      observed in granulosa, theca and luteal cells, and oocytes. Expression of SAA was
      also found in granulosa cells recovered from follicular aspirates. The SAA
      protein was detected in follicular fluids. Its levels were somewhat lower than in
      peripheral blood with strong correlation between the two compartments and with
      significant correlation with patient's body mass index. High follicular fluid SAA
      levels were associated with reduced pregnancy rate. CONCLUSIONS: SAA is locally
      produced in ovarian developing follicles and is a constituent of follicular
      fluids, suggesting its role within the follicular environment. Elevated
      follicular SAA levels are associated with decreased pregnancy rate and may
      signify lower reproductive performance.

PMID- 24030941
TI  - Localization of CaSR antagonists in CaSR-expressing medullary thyroid cancer.
AB  - OBJECTIVE: Image-based localization of medullary thyroid cancer (MTC) and
      parathyroid glands would improve the surgical outcomes of these diseases. MTC and
      parathyroid glands express high levels of calcium-sensing receptor (CaSR). The
      aim of this study was to prove the concept that CaSR antagonists specifically
      localize to CaSR-expressing tumors in vivo. DESIGN: We synthesized two isomers of
      a known CaSR calcilytic, Calhex 231, and four new analogs, which have a favorable
      structure for labeling. Their antagonistic activity was determined using
      immunoblots demonstrating decreased ERK1/2 phosphorylation after calcium
      stimulation in human embryonic kidney cells overexpressing CaSR. Compound 9 was
      further radiolabeled with (125)I and evaluated in nude mice with and without
      heterotransplanted xenografts of MTC cell lines, TT and MZ-CRC-1, that do and do
      not express CaSR, respectively. RESULTS: Two newly synthesized compounds, 9 and
      11, exhibited better antagonistic activity than Calhex 231. The half-life of
      (125)I-compound 9 in nude mice without xenografts was 9.9 hours. A
      biodistribution study in nude mice bearing both tumors demonstrated that the
      uptake of radioactivity in TT tumors was higher than in MZ-CRC-1 tumors at 24
      hours: 0.39 +/- 0.24 vs 0.18 +/- 0.12 percentage of injected dose per gram of
      tissue (%ID/g) (P = .002), with a ratio of 2.25 +/- 0.62. Tumor-to-background
      ratios for TT tumors, but not MZ-CRC-1 tumors, increased with time. Tumor-to
      blood values increased from 2.02 +/- 0.52 at 1 hour to 3.29 +/- 0.98 at 24 hour
      (P = .015) for TT tumors, and 1.7 +/- 0.56 at 1 hour to 1.48 +/- 0.33 at 24 hour
      (P = .36) for MZ-CRC-1 tumors. CONCLUSIONS: Our new CaSR antagonists specifically
      inhibit CaSR function in vitro, preferentially localize to CaSR-expressing tumors
      in vivo, and therefore have the potential to serve as scaffolds for further
      development as imaging pharmaceuticals.

PMID- 24030942
TI  - The characterization of pheochromocytoma and its impact on overall survival in
      multiple endocrine neoplasia type 2.
AB  - CONTEXT: Pheochromocytoma (PHEO) occurs in 50% of patients with multiple
      endocrine neoplasia type 2 (MEN2). It is unknown if the presence of PHEO is
      associated with more aggressive medullary thyroid cancer (MTC). OBJECTIVE: To
      present our experience with MEN2 PHEO and evaluate whether PHEO impacts MTC
      overall survival in patients with RET codon 634 mutations. DESIGN: We performed a
      retrospective chart review of MEN2 patients at MD Anderson Cancer Center from
      1960 through 2012. PATIENTS: The study group comprised 85 patients (group 1) with
      MEN2-associated PHEO. Of these, 59 patients (subgroup 1) with RET codon 634
      mutations were compared to 48 patients (group 2) with RET codon 634 mutations,
      but without MEN2-associated PHEO. MAIN OUTCOME MEASURES: Of 85 patients with MEN2
      and PHEO, 70 had MEN2A and 15 had MEN2B. Median age at PHEO diagnosis was 32
      years. The initial manifestation of MEN2 was MTC in 60% of patients, synchronous
      MTC and PHEO in 34%, and PHEO in 6% of patients. Of patients, 72% had bilateral
      PHEO, and most tumors were synchronous (82%). Subgroup analysis of MEN2 patients
      with and without PHEO, who were carriers of RET codon 634, the most common
      mutation with PHEO, showed no significant differences in the stage of MTC at
      initial diagnosis. The median follow-up time for patients with PHEO was 249
      months and without PHEO was 67 months (P < .01). Survival analyses among RET 634
      carriers did not show shorter survival for patients with PHEO. The median
      survival time for patients with PHEO was 499 months and without PHEO was 444
      months (P < .05). CONCLUSIONS: PHEO in MEN2 patients are usually bilateral and
      unlikely to be metastatic. Subgroup analysis of patients with RET 634 mutations
      with and without PHEO showed that PHEO was not associated with a more advanced
      stage of MTC at diagnosis or a shorter survival.

PMID- 24030943
TI  - Reduced insulin sensitivity in adults with pseudohypoparathyroidism type 1a.
AB  - CONTEXT: Disruption of the Gsalpha maternal allele leads to severe obesity and
      insulin resistance in mice and early-onset obesity in patients with
      pseudohypoparathyroidism (PHP) type 1a. However, insulin resistance and glucose
      metabolism have not been systematically characterized in patients with PHP1a.
      OBJECTIVE, DESIGN, AND SETTING: In a cross-sectional, case-control study, we
      examined insulin sensitivity, beta-cell function, energy expenditure (EE), and
      sympathetic nervous system activity in adults with PHP1a. STUDY PARTICIPANTS:
      PHP1a patients (n = 8) and healthy control subjects (n = 24) matched for age (41
      +/- 7 vs 41 +/- 7 years [mean +/- SD]), gender, and percent body fat. METHODS:
      Insulin sensitivity (SI), acute insulin response to glucose, and disposition
      index were assessed during a frequently sampled iv glucose tolerance test. Oral
      glucose insulin sensitivity (OGIS) was measured during a mixed meal. EE was
      measured using whole-room indirect calorimetry. Body composition was assessed via
      dual-energy x-ray absorptiometry and sympathetic nervous system activity by
      measuring 24-hour urinary catecholamine concentrations. RESULTS: PHP1a patients
      were less insulin-sensitive than their matched controls based upon SI and OGIS.
      Nondiabetic PHP1a patients tended to have a lower SI (P = .09) and reduced OGIS
      (P = .03). Disposition index, a composite measure of beta-cell function, also
      tended to be lower in patients (P = .07). Total caloric intake, resting EE, total
      EE, meal-induced thermogenesis, and 24-hour urinary catecholamine concentrations
      were not significantly different between the groups. CONCLUSIONS: Adults with PHP
      1a have reduced insulin sensitivity compared with their matched controls that may
      contribute to the pathogenesis of glucose intolerance and diabetes in these
      patients.

PMID- 24030944
TI  - Update in mortality in GH-treated patients.
AB  - During GH therapy for 2.3-9.6 years, male adult-onset GH-deficient patients with
      a diagnosis of a nonfunctioning adenoma have no increased all-cause mortality.
      However, women with adult-onset GH deficiency (GHD) are still at slightly higher
      risk. This general improvement in mortality is due to a more contemporary regimen
      of cardiovascular drugs, a refinement of surgical procedures, besides the
      introduction of GH therapy improved hormone replacement regimens with lowered
      glucocorticoid replacement, updated approaches of sex steroids for women, and
      less use of cranial radiotherapy. The underlying disease is the most important
      predictor for mortality: eg, a craniopharyngioma, malignant causes of
      hypopituitarism, previous Cushing's disease, and the presence of diabetes
      insipidus/aggressive tumors. The main cause of increased mortality was
      cerebrovascular diseases and infectious/respiratory diseases in ACTH-deficient
      patients. Furthermore, there was a significant impact of young age at disease
      onset and of death from secondary brain tumors, with a higher risk after cranial
      radiotherapy. Reports on four cohorts of GH-treated childhood-onset GHD patients
      have been published. Two of them included only patients with idiopathic isolated
      GHD, neurosecretory dysfunction, idiopathic short stature, or being born short
      for gestational age. Increased mortality in circulatory disorders, ill-defined
      diseases, and bone cancer were recorded in one study, but not in the other
      smaller study, where suicide and accidents caused the majority of deaths. A third
      childhood-onset GHD cohort included patients with a background of malignant
      tumors, craniopharyngioma, pituitary adenomas, pituitary aplasia/hypoplasia, and
      trauma. An increase of all-cause mortality was recorded in both males and
      females. The fourth cohort included isolated GHD and idiopathic short stature
      (60%), but also diagnosis of chronic renal failure and Turner's syndrome. In
      these latter studies, an underlying serious condition was the most important
      factor for death, with central nervous system tumors (recurrent or new tumor)
      being the leading cause of mortality. 

PMID- 24030945
TI  - Twice-daily subcutaneous injection of kisspeptin-54 does not abolish menstrual
      cyclicity in healthy female volunteers.
AB  - BACKGROUND: Kisspeptin is a critical hypothalamic regulator of reproductive
      function. Chronic kisspeptin administration causes profound tachyphylaxis in male
      monkeys and in women with functional hypothalamic amenorrhea. The pharmacological
      effects of chronic kisspeptin exposure in healthy women with normal menstrual
      cycles have not been studied previously. AIM: Our aim was to determine the
      effects of follicular-phase kisspeptin-54 treatment on menstrual cyclicity in
      healthy women. METHODS: We performed a prospective, single-blinded, 1-way
      crossover study. Healthy women received twice-daily sc injections of kisspeptin
      (6.4 nmol/kg) or 0.9% saline during menstrual days 7-14 (n = 5 per treatment
      arm). Serial assessments of basal reproductive hormones, ultrasound parameters,
      LH pulsatility, and acute sensitivity to GnRH and kisspeptin-54 injection were
      performed. RESULTS: Menstrual cyclicity persisted in all women after follicular
      phase kisspeptin-54 treatment. Chronic exposure to kisspeptin-54 did not abolish
      acute stimulation of LH after injection of kisspeptin-54 or GnRH. In addition,
      kisspeptin-54 treatment was associated with a shorter mean length of the
      menstrual cycle (mean length of menstrual cycle was 28.6 +/- 1.4 days with saline
      vs 26.8 +/- 3.1 days with kisspeptin, P < .01), earlier onset of highest recorded
      serum LH (mean menstrual day of highest LH was 15.2 +/- 1.3 with saline vs 13.0
      +/- 1.9 with kisspeptin, P < .05), and earlier onset of the luteal phase (mean
      menstrual day of progesterone increase was 18.0 +/- 2.1 with saline vs 15.8 +/-
      0.9 with kisspeptin, P < .05). CONCLUSION: Our data suggest that 1 week of
      exogenous kisspeptin-54 does not abolish menstrual cyclicity in healthy women.
      Further work is needed to determine whether kisspeptin could be used to treat
      certain anovulatory disorders.

PMID- 24030946
TI  - Effects of pioglitazone on visceral fat metabolic activity in impaired glucose
      tolerance or type 2 diabetes mellitus.
AB  - CONTEXT: Excess visceral fat is associated with chronic systemic inflammation and
      cardiovascular complications. Pioglitazone has been reported to variably
      influence visceral fat volume; however, its effect on metabolic activity of the
      visceral fat remains uncharacterized. OBJECTIVE: The aim of this study was to
      assess the effects of pioglitazone on glucose metabolism of fat tissue by using
      (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed
      tomography imaging. DESIGN, SETTING, AND PARTICIPANTS: FDG-PET and computed
      tomography imaging were performed in 56 patients with impaired glucose tolerance
      or type 2 diabetes mellitus; lipid and glycemic profiles and inflammatory
      biomarkers were obtained in all patients. These patients were randomized to
      treatment with either pioglitazone or glimepiride for 16 weeks. MAIN OUTCOME
      MEASURES: The metabolic activity of the visceral fat tissues as assessed by FDG
      uptake was expressed as a target-to-background ratio (TBR) of blood-normalized
      standardized uptake value. RESULTS: The study was completed in 32 pioglitazone
      treated and 21 glimepiride-treated patients (40 men and 13 women; mean age, 67.7
      +/- 8.1 y; body mass index, 25.0 +/- 3.6 kg/m(2); glycated hemoglobin, 6.78 +/-
      0.70%). Both treatments were well-tolerated and comparably improved glycemic
      control. At baseline, visceral fat exhibited a higher TBR value than subcutaneous
      fat (0.55 +/- 0.14 vs 0.30 +/- 0.07, P < .001). Pioglitazone, but not
      glimepiride, significantly decreased the visceral fat volume (130.5 +/- 53.0 to
      122.1 +/- 51.0 cm(2), P = .013) and TBR values (0.57 +/- 0.16 to 0.50 +/- 0.11, P
      = .007). Neither pioglitazone nor glimepiride treatment showed any effect on the
      volume or TBR values of subcutaneous fat. After 16 weeks of treatment with
      pioglitazone, reduction in visceral fat TBR was correlated to the increase in
      high-density lipoprotein cholesterol levels. CONCLUSIONS: Our study indicated
      that pioglitazone decreased the visceral fat volume and its metabolic activity in
      patients with impaired glucose tolerance or type 2 diabetes mellitus. The
      beneficial effects of pioglitazone on visceral fat may be independent of its
      glucose-lowering effect.

PMID- 24030948
TI  - Genotype-phenotype correlations in hyperekplexia: apnoeas, learning difficulties
      and speech delay.
AB  - Congenital hyperekplexia is a rare, potentially treatable neuromotor disorder.
      Three major genes of effect are known, and all three affect glycinergic
      neurotransmission. Two genes encode for subunits of the postsynaptic inhibitory
      glycine receptor, GLRA1 encoding the alpha1 subunit and GLRB encoding the beta
      subunit. The third, SLC6A5, encodes the cognate presynaptic glycine transporter
      2. Ninety-seven individuals had a clinical diagnosis of hyperekplexia confirmed
      by genetic testing: 61 cases had mutations in GLRA1, 24 cases in SLC6A5 and 12 in
      GLRB. Detailed retrospective clinical analysis ascertained that all gene-positive
      cases present in the neonatal period (occasionally prenatally) and that
      clonazepam is the treatment of choice (95% found it to be efficacious). We
      confirm that hyperekplexia is predominantly a recessive condition but dominant
      cases are seen (16%). We found no genetic evidence for 'major' or 'minor' forms
      of hyperekplexia on a population basis. Thirty-five gene-negative cases were
      studied for comparison, their cardinal feature was presentation after the first
      month of life (P < 0.001). In addition to the characteristic 'stiffness, startles
      and stumbles' of hyperekplexia, apnoea attacks (50 of 89) and delayed development
      (47 of 92) were frequently reported. Patients with SLC6A5 mutations were
      significantly more likely to have had recurrent infantile apnoeas (RR1.9; P <
      0.005) than those with GLRA1 mutations. Patients with GLRB and SLC6A5 mutations
      were more likely to have developmental delay (RR1.5 P < 0.01; RR1.9 P < 0.03)
      than those with GLRA1 mutations; 92% of GLRB cases reported a mild to severe
      delay in speech acquisition. Molecular modelling of pathogenic mutations
      demonstrates specific patterns of protein disruption that can be used to predict
      phenotype severity. The developmental delay in hyperekplexia, and speech
      acquisition in particular, may represent failure of developmental neural networks
      or subtle neurogenic migration defects in the absence of presynaptic glycine
      release. We recommend early genetic testing for symptomatic neonates and possibly
      preconception counselling for those at risk for GLRB and SLC6A5 mutations,
      because of the more challenging phenotype. 

PMID- 24030947
TI  - Large scale genotype-phenotype analyses indicate that novel prognostic tools are
      required for families with facioscapulohumeral muscular dystrophy.
AB  - Facioscapulohumeral muscular dystrophy has been genetically linked to reduced
      numbers (<= 8) of D4Z4 repeats at 4q35 combined with 4A(159/161/168) DUX4
      polyadenylation signal haplotype. However, we have recently reported that 1.3% of
      healthy individuals carry this molecular signature and 19% of subjects affected
      by facioscapulohumeral muscular dystrophy do not carry alleles with eight or
      fewer D4Z4 repeats. Therefore, prognosis for subjects carrying or at risk of
      carrying D4Z4 reduced alleles has become more complicated. To test for additional
      prognostic factors, we measured the degree of motor impairment in a large group
      of patients affected by facioscapulohumeral muscular dystrophy and their
      relatives who are carrying D4Z4 reduced alleles. The clinical expression of motor
      impairment was assessed in 530 subjects, 163 probands and 367 relatives, from 176
      unrelated families according to a standardized clinical score. The associations
      between clinical severity and size of D4Z4 allele, degree of kinship, gender, age
      and 4q haplotype were evaluated. Overall, 32.2% of relatives did not display any
      muscle functional impairment. This phenotype was influenced by the degree of
      relation with proband, because 47.1% of second- through fifth-degree relatives
      were unaffected, whereas only 27.5% of first-degree family members did not show
      motor impairment. The estimated risk of developing motor impairment by age 50 for
      relatives carrying a D4Z4 reduced allele with 1-3 repeats or 4-8 repeats was
      88.7% and 55%, respectively. Male relatives had a mean score significantly higher
      than females (5.4 versus 4.0, P = 0.003). No 4q haplotype was exclusively
      associated with the presence of disease. In 13% of families in which D4Z4 alleles
      with 4-8 repeats segregate, the diagnosis of facioscapulohumeral muscular
      dystrophy was reported only in one generation. In conclusion, this large-scale
      analysis provides further information that should be taken into account when
      counselling families in which a reduced allele with 4-8 D4Z4 repeats segregates.
      In addition, the reduced expression of disease observed in distant relatives
      suggests that a family's genetic background plays a role in the occurrence of
      facioscapulohumeral muscular dystrophy. These results indicate that the
      identification of new susceptibility factors for this disease will require an
      accurate classification of families.

PMID- 24030949
TI  - Impairment only on the fluency subtest of the Frontal Assessment Battery after
      prefrontal lesions.
AB  - The Frontal Assessment Battery is a set of six subtests that is used widely to
      assess frontal cortical executive dysfunction. Performance on the Frontal
      Assessment Battery has been shown to be sensitive to various neurodegenerative
      diseases, but it has never been shown to be sensitive to damage restricted to the
      frontal cortex. Thus, despite its wide use, it has never been validated on an
      appropriate population of patients with frontal lesions. The present study shows
      that, of the six subtests that comprise the Frontal Assessment Battery, only
      performance on the verbal fluency subtest (mental flexibility) was specifically
      sensitive to injury restricted to the frontal cortex. Performance of patients
      with damage to the dorsal part of the medial frontal region in the language
      dominant left hemisphere was impaired. None of these patients was aphasic at the
      time of testing. The critical region in the dorsomedial frontal cortex includes
      the supplementary speech zone but is not restricted to it: it extends into the
      cingulate motor region and the paracingulate cortex as well as the medial
      prefrontal areas 8 and 9. The results indicate that the Frontal Assessment
      Battery is not a sensitive measure of prefrontal cortical dysfunction, except for
      the verbal fluency subtest. 

PMID- 24030950
TI  - Defective autophagy in spastizin mutated patients with hereditary spastic
      paraparesis type 15.
AB  - Hereditary spastic paraparesis type 15 is a recessive complicated form of the
      disease clinically characterized by slowly progressive spastic paraparesis and
      mental deterioration with onset between the first and second decade of life.
      Thinning of corpus callosum is the neuroradiological distinctive sign frequently
      associated with white matter abnormalities. The causative gene, ZFYVE26, encodes
      a large protein of 2539 amino acid residues, termed spastizin, containing three
      recognizable domains: a zinc finger, a leucine zipper and a FYVE domain.
      Spastizin protein has a diffuse cytoplasmic distribution and co-localizes
      partially with early endosomes, the endoplasmic reticulum, microtubules and
      vesicles involved in protein trafficking. In addition, spastizin localizes to the
      mid-body during the final step of mitosis and contributes to successful
      cytokinesis. Spastizin interacts with Beclin 1, a protein required for
      cytokinesis and autophagy, which is the major lysosome-mediated degradation
      process in the cell. In view of the Beclin 1-spastizin interaction, we
      investigated the possible role of spastizin in autophagy. We carried out this
      analysis by using lymphoblast and fibroblast cells derived from four different
      spastizin mutated patients (p.I508N, p.L243P, p.R1209fsX, p.S1312X) and from
      control subjects. Of note, the truncating p.R1209fsX and p.S1312X mutations lead
      to loss of spastizin protein. The results obtained indicate that spastizin
      interacts with the autophagy related Beclin 1-UVRAG-Rubicon multiprotein complex
      and is required for autophagosome maturation. In cells lacking spastizin or with
      mutated forms of the protein, spastizin interaction with Beclin 1 is lost
      although the formation of the Beclin 1-UVRAG-Rubicon complex can still be
      observed. However, in these cells we demonstrate an impairment of autophagosome
      maturation and an accumulation of immature autophagosomes. Autophagy defects with
      autophagosome accumulation can be observed also in neuronal cells upon spastizin
      silencing. These results indicate that autophagy is a central process in the
      pathogenesis of complicated forms of hereditary spastic paraparesis with thin
      corpus callosum.

PMID- 24030951
TI  - DNA methylation map of mouse and human brain identifies target genes in
      Alzheimer's disease.
AB  - The central nervous system has a pattern of gene expression that is closely
      regulated with respect to functional and anatomical regions. DNA methylation is a
      major regulator of transcriptional activity, and aberrations in the distribution
      of this epigenetic mark may be involved in many neurological disorders, such as
      Alzheimer's disease. Herein, we have analysed 12 distinct mouse brain regions
      according to their CpG 5'-end gene methylation patterns and observed their unique
      epigenetic landscapes. The DNA methylomes obtained from the cerebral cortex were
      used to identify aberrant DNA methylation changes that occurred in two mouse
      models of Alzheimer's disease. We were able to translate these findings to
      patients with Alzheimer's disease, identifying DNA methylation-associated
      silencing of three targets genes: thromboxane A2 receptor (TBXA2R), sorbin and
      SH3 domain containing 3 (SORBS3) and spectrin beta 4 (SPTBN4). These
      hypermethylation targets indicate that the cyclic AMP response element-binding
      protein (CREB) activation pathway and the axon initial segment could contribute
      to the disease. 

PMID- 24030952
TI  - Next generation sequencing for molecular diagnosis of neurological disorders
      using ataxias as a model.
AB  - Many neurological conditions are caused by immensely heterogeneous gene
      mutations. The diagnostic process is often long and complex with most patients
      undergoing multiple invasive and costly investigations without ever reaching a
      conclusive molecular diagnosis. The advent of massively parallel, next-generation
      sequencing promises to revolutionize genetic testing and shorten the 'diagnostic
      odyssey' for many of these patients. We performed a pilot study using
      heterogeneous ataxias as a model neurogenetic disorder to assess the introduction
      of next-generation sequencing into clinical practice. We captured 58 known human
      ataxia genes followed by Illumina Next-Generation Sequencing in 50 highly
      heterogeneous patients with ataxia who had been extensively investigated and were
      refractory to diagnosis. All cases had been tested for spinocerebellar ataxia 1
      3, 6, 7 and Friedrich's ataxia and had multiple other biochemical, genetic and
      invasive tests. In those cases where we identified the genetic mutation, we
      determined the time to diagnosis. Pathogenicity was assessed using a
      bioinformatics pipeline and novel variants were validated using functional
      experiments. The overall detection rate in our heterogeneous cohort was 18% and
      varied from 8.3% in those with an adult onset progressive disorder to 40% in
      those with a childhood or adolescent onset progressive disorder. The highest
      detection rate was in those with an adolescent onset and a family history (75%).
      The majority of cases with detectable mutations had a childhood onset but most
      are now adults, reflecting the long delay in diagnosis. The delays were primarily
      related to lack of easily available clinical testing, but other factors included
      the presence of atypical phenotypes and the use of indirect testing. In the cases
      where we made an eventual diagnosis, the delay was 3-35 years (mean 18.1 years).
      Alignment and coverage metrics indicated that the capture and sequencing was
      highly efficient and the consumable cost was ~L400 (?460 or US$620). Our
      pathogenicity interpretation pathway predicted 13 different mutations in eight
      different genes: PRKCG, TTBK2, SETX, SPTBN2, SACS, MRE11, KCNC3 and DARS2 of
      which nine were novel including one causing a newly described recessive ataxia
      syndrome. Genetic testing using targeted capture followed by next-generation
      sequencing was efficient, cost-effective, and enabled a molecular diagnosis in
      many refractory cases. A specific challenge of next-generation sequencing data is
      pathogenicity interpretation, but functional analysis confirmed the pathogenicity
      of novel variants showing that the pipeline was robust. Our results have broad
      implications for clinical neurology practice and the approach to diagnostic
      testing. 

PMID- 24030953
TI  - Purkinje cell axonal anatomy: quantifying morphometric changes in essential
      tremor versus control brains.
AB  - Growing clinical, neuro-imaging and post-mortem data have implicated the
      cerebellum as playing an important role in the pathogenesis of essential tremor.
      Aside from a modest reduction of Purkinje cells in some post-mortem studies,
      Purkinje cell axonal swellings (torpedoes) are present to a greater degree in
      essential tremor cases than controls. Yet a detailed study of more subtle
      morphometric changes in the Purkinje cell axonal compartment has not been
      undertaken. We performed a detailed morphological analysis of the Purkinje cell
      axonal compartment in 49 essential tremor and 39 control brains, using calbindin
      D28k immunohistochemistry on 100-um cerebellar cortical vibratome tissue
      sections. Changes in axonal shape [thickened axonal profiles (P = 0.006),
      torpedoes (P = 0.038)] and changes in axonal connectivity [axonal recurrent
      collaterals (P < 0.001), axonal branching (P < 0.001), terminal axonal sprouting
      (P < 0.001)] were all present to an increased degree in essential tremor cases
      versus controls. The changes in shape and connectivity were significantly
      correlated [e.g. correlation between thickened axonal profiles and recurrent
      collaterals (r = 0.405, P < 0.001)] and were correlated with tremor duration
      among essential tremor cases with age of onset >40 years. In essential tremor
      cases, thickened axonal profiles, axonal recurrent collaterals and branched axons
      were 3- to 5-fold more frequently seen on the axons of Purkinje cells with
      torpedoes versus Purkinje cells without torpedoes. We document a range of changes
      in the Purkinje cell axonal compartment in essential tremor. Several of these are
      likely to be compensatory changes in response to Purkinje cell injury, thus
      illustrating an important feature of Purkinje cells, which is that they are
      relatively resistant to damage and capable of mobilizing a broad range of axonal
      responses to injury. The extent to which this plasticity of the Purkinje cell
      axon is partially neuroprotective or ultimately ineffective at slowing further
      cellular changes and cell death deserves further study in essential tremor. 

PMID- 24030954
TI  - Proteomic changes in chicken primary hepatocytes exposed to T-2 toxin are
      associated with oxidative stress and mitochondrial enhancement.
AB  - T-2 toxin is a mycotoxin that is toxic to plants, animals, and humans. However,
      its molecular mechanism remains unclear, especially in chickens. In this study,
      using 2D electrophoresis with MALDI-TOF/TOF-MS, 53 proteins were identified as up
      or downregulated by T-2 toxin in chicken primary hepatocytes. Functional network
      analysis by ingenuity pathway analysis showed that the top network altered by T-2
      toxin is associated with neurological disease, cancer, organismal injury, and
      abnormalities. Most of the identified proteins were associated with one of eight
      functional classes, including cell redox homeostasis, transcriptional or
      translational regulation, cell cycle or cell proliferation, stress response,
      lipid metabolism, transport, carbohydrate metabolism, and protein degradation.
      Subcellular location categorization showed that the identified proteins were
      predominantly located in the mitochondrion (34%) and interestingly, the
      expression of all the identified mitochondrial proteins was increased. Further
      cellular analysis showed that T-2 toxin was able to induce the ROS accumulation
      and could lead to an increase in mitochondrial mass and adenosine 5'-triphosphate
      content, which indicated that oxidative stress and mitochondrial enhancement
      occurred in T-2 toxin-treated cells. Overall, these results characterize the
      global proteomic response of chicken primary hepatocytes to T-2 toxin, which may
      lead to a better understanding of the molecular mechanisms underlying its
      toxicity. 

PMID- 24030955
TI  - Semiconducting polymer dots doped with europium complexes showing ultranarrow
      emission and long luminescence lifetime for time-gated cellular imaging.
AB  - Bright dots: Semiconducting polymer dots (Pdots) doped with europium complexes
      possess line-like fluorescence emission, high quantum yield, and long
      fluorescence lifetime. The Pdots successfully labeled receptors on cells. The
      long fluorescence lifetime of the Pdots was used to distinguish them from other
      red fluorescence emitting nanoparticles, and improve the signal-to-noise ratio
      for time-gated cellular imaging. PVK=poly(9-vinylcarbazole). 

PMID- 24030956
TI  - Device closure of patent foramen ovale in cryptogenic stroke: still stuck in
      hamlet mode.

PMID- 24030957
TI  - COMP-Ang1 accelerates chondrocyte maturation by decreasing HO-1 expression.
AB  - Endochondral ossification is essential for new bone formation and remodeling
      during the distraction stage. Endochondral ossification is attributed to
      chondrocyte maturation, which is induced by various factors, such as the cellular
      environment, gene transcription, and growth factor expression. Cartilage
      oligomeric matrix protein (COMP)-angiopoietin 1 (Ang1) is more soluble, stable,
      and potent than endogenous Ang1, and COMP-Ang1 treatment has osteogenic and
      angiogenic effects in an in vivo model of bone fracture healing. Although the
      osteogenic effects of COMP-Ang1 have been demonstrated, the precise mechanism by
      which COMP-Ang1 induces chondrocyte maturation and triggers endochondral
      ossification is not understood. Here, we investigated the possible mechanism by
      which COMP-Ang1 induces chondrocyte maturation. First, using a WST assay, we
      found that COMP-Ang1 is nontoxic in rat chondrocytes. Then, we isolated total RNA
      from COMP-Ang1-treated rat chondrocytes, and analyzed the decrease in
      chondrogenic gene expression and the increase in osteogenic gene expression using
      real-time RT-PCR. Gene and protein expression of heme oxygenase-1 (HO-1), which
      maintains chondrocytes in an immature stage, decreased in a dose-dependent manner
      upon COMP-Ang1 treatment. To clarify the relationship between HO-1 and COMP-Ang1
      in chondrocyte maturation, we used cobalt protoporphyrin IX (CoPP IX), an HO-1
      inducer, and tin protoporphyrin IX (SnPP-IX), an HO-1 inhibitor. Treatment with
      various combinations of CoPP IX, SnPP IX, and COMP-Ang1 confirmed that COMP-Ang1
      accelerates chondrocyte maturation by reducing HO-1. In conclusion, our results
      suggest that COMP-Ang1 accelerates chondrocyte maturation by interacting with HO
      1.

PMID- 24030958
TI  - Piezoelectric properties of aligned collagen membranes.
AB  - Electromechanical coupling, a phenomenon present in collagenous materials, may
      influence cell-extracellular matrix interactions. Here, electromechanical
      coupling has been investigated via piezoresponse force microscopy in transparent
      and opaque membranes consisting of helical-like arrays of aligned type I collagen
      fibrils self-assembled from acidic solution. Using atomic force microscopy, the
      transparent membrane was determined to contain fibrils having an average diameter
      of 76 +/- 14 nm, whereas the opaque membrane comprised fibrils with an average
      diameter of 391 +/- 99 nm. As the acidity of the membranes must be neutralized
      before they can serve as cell culture substrates, the structure and piezoelectric
      properties of the membranes were measured under ambient conditions before and
      after the neutralization process. A crimp structure (1.59 +/- 0.37 um in width)
      perpendicular to the fibril alignment became apparent in the transparent membrane
      when the pH was adjusted from acidic (pH = 2.5) to neutral (pH = 7) conditions.
      In addition, a 1.35-fold increase was observed in the amplitude of the shear
      piezoelectricity of the transparent membrane. The structure and piezoelectric
      properties of the opaque membrane were not significantly affected by the
      neutralization process. The results highlight the presence of an additional
      translational order in the transparent membrane in the direction perpendicular to
      the fibril alignment. The piezoelectric response of both membrane types was found
      to be an order of magnitude lower than that of collagen fibrils in rat tail
      tendon. This reduced response is attributed to less-ordered molecular assembly
      than is present in D-periodic collagen fibrils, as evidenced by the absence of D
      periodicity in the membranes.

PMID- 24030961
TI  - Contents: macromol. Rapid commun. 18/2013.

PMID- 24030959
TI  - High throughput screening of disulfide-containing proteins in a complex mixture.
AB  - The formation of disulfide bonds between cysteine residues is crucial for the
      stabilization of native protein structures and, thus, determination of disulfide
      linkages is an important facet of protein structural characterization.
      Nonetheless, the identification of disulfide bond linkages remains a significant
      analytical challenge, particularly in large proteins with complex disulfide
      patterns. Herein, we have developed a new LC/MS strategy for rapid screening of
      disulfides in an intact protein mixture after a straightforward reduction step
      with tris(2-carboxyethyl)phosphine. LC/MS analysis of reduced and nonreduced
      protein mixtures quickly revealed disulfide-containing proteins owing to a 2 Da
      mass increase per disulfide reduction and, subsequently, the total number of
      disulfide bonds in the intact proteins could be determined. We have demonstrated
      the effectiveness of this method in a protein mixture composed of both disulfide
      containing and disulfide-free proteins. Our method is simple (no need for
      proteolytic digestion, alkylation, or the removal of reducing agents prior to MS
      analysis), high throughput (fast on-line LC/MS analysis), and reliable (no S-S
      scrambling), underscoring its potential as a rapid disulfide screening method for
      proteomics applications. 

PMID- 24030962
TI  - Optically active particles of chiral polymers.
AB  - Particles constructed by chiral polymers (defined as PCPs) have emerged as a
      rapidly expanding research field in recent years because of their potentially
      wide-ranging applications in asymmetric catalysis, enantioselective
      crystallization, enantioselective release, amongst many others. The particles
      show considerable optical activity, due to the chirality of the corresponding
      polymers from which the particles are derived. This review article presents an
      overview on PCPs with emphasis on our group's recent achievements in the
      preparation of PCPs derived from optically active helical polymers and their
      applications. PCPs can be prepared via emulsion polymerization, precipitation
      polymerization, and suspension polymerization by starting from monomers.
      Emulsification of preformed chiral polymers and self-assembly approaches also can
      lead to PCPs. Chiral polymer-based core/shell particles, hollow particles, and
      magnetic particles are also covered because of their remarkable properties and
      significant potential applications. 

PMID- 24030963
TI  - Convenient pd-catalyzed synthesis of large unimolecular star polyethylene
      nanoparticles.
AB  - A simplistic convenient "arm-first" catalytic synthesis method is demonstrated to
      render soft unimolecular star polyethylene nanoparticles. Low-dispersity
      polyethylene arms of controllable length and topology are first synthesized via
      Pd-catalyzed "living" ethylene poly-merization. The subsequent addition of
      norbornadiene as a unique cross-linker renders the block polymer containing a
      short polynorbornadiene (PNBD) sequence. Efficient and rapid catalytic cross
      linking of the PNBD sequences occurs in the polymer precipitation and drying
      steps to give rise to star polyethylene nanoparticles. The star polymers are
      featured with tunable arm length and topology, high molecular weight (as high as
      1770 kg mol-1), high arm numbers (as high as 88), and desirable average nano
      particle size (29-72 nm).

PMID- 24030966
TI  - Phenylethynylcobalamin: a light-stable and thermolysis-resistant organometallic
      vitamin B(12) derivative prepared by radical synthesis.
AB  - Don't take this antivitamin! 2-Phenylethynylcobalamin was prepared in a newly
      developed radical reaction using cob(II)alamin and 1-iodo-2-phenylethyne. It has
      an exceptionally short organometallic bond and is a remarkably light-stable and
      heat-resistant organometallic cobalamin. It is bound well by two important
      proteins of the human B12 transport system and has properties that are as
      expected for a new type of an "antivitamin B12 ". 

PMID- 24030967
TI  - Non-surgical treatments for anal fissure in adults.
AB  - An anal fissure is defined as a linear tear or ulcer of the anal mucosa. Patients
      typically describe a sharp pain 'like passing broken glass' on defaecation,
      followed by a burning pain in the anus lasting a few hours. Pain and bleeding
      during and after the passage of stool are the usual presenting features. Fissures
      are most common in young to middle-aged adults and are also commonly seen in
      pregnant and postpartum women. The lifetime incidence of anal fissure is around
      11%. Here, we review the evidence on the efficacy and safety of non-surgical
      treatments for anal fissure.

PMID- 24030968
TI  - Dapagliflozin (Forxiga) for type 2 diabetes?
AB  - In the UK, diabetes mellitus affects around 3 million people, of whom over 90%
      have type 2 diabetes. Aims of treatment include minimising long-term
      complications (e.g. cardiovascular disease, blindness, chronic kidney disease,
      premature mortality) and avoiding unwanted effects of treatment (e.g. severe
      hypoglycaemia, weight gain). Management of diabetes includes patient support and
      education; addressing symptoms; lifestyle modification; targeting associated risk
      factors for cardiovascular disease; and surveillance for, and management of,
      complications including treatment-related hypoglycaemia. Dapagliflozin (Forxiga)
      belongs to a new class of oral glucose-lowering drugs that inhibit renal glucose
      reabsorption and promote glycosuria. It is licensed in the UK in adults with type
      2 diabetes as monotherapy when diet and exercise alone do not provide adequate
      glycaemic control and who are unable to tolerate metformin; or, as add-on
      therapy, with other glucose-lowering agents including insulin, when these, with
      diet and exercise, do not provide adequate glycaemic control. The company's
      advertising materials claim that dapagliflozin provides a "novel method of
      controlling excess glucose" with "secondary benefit of weight loss". Here, we
      review the evidence for the use of dapagliflozin in the management of type 2
      diabetes mellitus.

PMID- 24030969
TI  - Ocelot catheter for the treatment of long SFA occlusion.
AB  - Long saphenous femoral artery (SFA) chronic total occlusions (CTOs) are
      considered the "Achilles heel" of the lower extremity percutaneous interventions.
      Antegrade, retrograde, or transcollateral approaches, intraluminal or subintimal
      techniques with re-entry and specialized CTO devices using microdissection,
      vibrational energy, and laser have all been tried for the management of such
      challenging lesions with various success rates. Ocelot is the first CTO crossing
      device using real-time OCT technology. Its crossing catheter utilizes spiral
      wedges to corkscrew the CTO cap, while real-time OCT offers direct visualization
      to facilitate intravascular true-lumen orientation. The recently presented
      results of the CONNECT-II study demonstrated crossing success of 97% and freedom
      from major adverse events of 98%. We present one of the most challenging SFA CTOs
      with ambiguous proximal cap in the ostium of the SFA, heavy calcification and
      involving almost the entire length of the SFA. The Ocelot catheter assisted to
      the successful true-lumen recanalization of that complex lesion.

PMID- 24030970
TI  - Energy metabolism characterization of a novel cancer stem cell-like line 3AB-OS.
AB  - Cancer stem cells (CSC) have a central role in driving tumor growth. Since
      metabolism is becoming an important diagnostic and therapeutic target,
      characterization of CSC line energetic properties is an emerging need. Embryonic
      and adult stem cells, compared to differentiated cells, exhibit a reduced
      mitochondrial activity and a stronger dependence on aerobic glycolysis. Here, we
      aimed to comparatively analyze bioenergetics features of the human osteosarcoma
      3AB-OS CSC-like line, and the parental osteosarcoma MG63 cells, from which 3AB-OS
      cells have been previously selected. Our results suggest that 3AB-OS cells depend
      on glycolytic metabolism more strongly than MG63 cells. Indeed, growth in glucose
      shortage or in presence of galactose or pyruvate (mitochondrial specific
      substrates) leads to a significant reduction of their proliferation compared to
      MG63 cells. Accordingly, 3AB-OS cells show an increased expression of lactate
      dehydrogenase A (LDHA) and a larger accumulation of lactate in the culture
      medium. In line with these findings 3AB-OS cells as compared to MG63 cells
      present a reduced mitochondrial respiration, a stronger sensitivity to glucose
      depletion or glycolysis inhibition and a lessened sensitivity to oxidative
      phosphorylation inhibitors. Additionally, in contrast to MG63 cells, 3AB-OS
      display fragmented mitochondria, which become networked as they grow in glucose
      rich medium, while almost entirely loose these structures growing in low glucose.
      Overall, our findings suggest that 3AB-OS CSC energy metabolism is more similar
      to normal stem cells and to cancer cells characterized by a glycolytic anaerobic
      metabolism.

PMID- 24030971
TI  - Facile synthesis of thiol-functionalized long-chain highly branched ROMP polymers
      and surface-decorated with gold nanoparticles.
AB  - The synthesis of thiol-functionalized long-chain highly branched polymers
      (LCHBPs) has been accomplished in combination of ring-opening metathesis
      polymerization (ROMP) and thiol-Michael addition click reaction. A monotelechelic
      polymer with a terminal acrylate and many pendent thiol groups is first prepared
      through adding an internal cis-olefin terminating agent to the reaction mixture
      immediately after the completion of the living ROMP, and then utilized as an ABn 
      type macromonomer in subsequent thiol-ene reaction between acrylate and thiol,
      yielding LCHBPs as the reaction time prolonged. Au nanoparticles are then
      covalently conjugated onto the surface of thiol-functionalized LCHBP to fabricate
      novel hybrid nanostructures, which is shown as one interesting application of
      such functionalized metathesis polymers. This facile approach can be extended
      toward the fabrication of novel nanomaterials with sophisticated structures and
      tunable multifunctionalities. 

PMID- 24030972
TI  - Evaluation of ubiquitinated proteins by proteomics reveals the role of the
      ubiquitin proteasome system in the regulation of Grp75 and Grp78 chaperone
      proteins during intestinal inflammation.
AB  - The ubiquitin proteasome system (UPS) is the major pathway of intracellular
      protein degradation and may be involved in the pathophysiology of inflammatory
      bowel diseases or irritable bowel syndrome. UPS specifically degrades proteins
      tagged with an ubiquitin chain. We aimed to identify polyubiquitinated proteins
      during inflammatory response in intestinal epithelial HCT-8 cells by a proteomic
      approach. HCT-8 cells were incubated with interleukin 1beta, tumor necrosis
      factor-alpha, and interferon-gamma for 2 h. Total cellular protein extracts were
      separated by 2D gel electrophoresis and analyzed by an immunodetection using
      antiubiquitin antibody. Differential ubiquitinated proteins were then identified
      by LC-ESI MS/MS. Seven proteins were differentially ubiquitinated between control
      and inflammatory conditions. Three of them were chaperones: Grp75 and Hsc70 were
      more ubiquitinated (p < 0.05) and Grp78 was less ubiquitinated (p < 0.05) under
      inflammatory conditions. The results for Grp75 and Grp78 were then confirmed in
      HCT-8 cells and in 2-4-6-trinitrobenzen sulfonic acid induced colitis in rats
      mimicking inflammatory bowel disease by immunoprecipitation. No difference was
      observed in irritable bowel syndrome like model. In conclusion, we showed that a
      proteomic approach is suitable to identify ubiquitinated proteins and that UPS
      regulated expression of Grp75 and Grp78 may be involved in inflammatory response.
      Further studies should lead to the identification of ubiquitin ligases
      responsible for Grp75 and Grp78 ubiquitination. 

PMID- 24030973
TI  - Current strategies in meniscal regeneration.
AB  - The meniscus plays an important role in the biomechanics and tribology of the
      knee joint. Damage to or disease of the meniscus is now recognized to predispose
      to the development of osteoarthritis. Treatment of meniscal injury through
      arthroscopic surgery has become one of the most common orthopedic surgical
      procedures, and in the United States this can represent 10 to 20% of procedures
      related to the knee. The meniscus has a limited healing capacity constrained to
      the vascularized periphery and therefore, surgical repair of the avascular
      regions is not always feasible. Replacement and repair of the meniscus to treat
      injuries is being investigated using tissue engineering strategies. Promising as
      these approaches may be, there are, however, major barriers to overcome before
      translation to the clinic.

PMID- 24030974
TI  - Cascading of molecular logic gates for advanced functions: a self-reporting,
      activatable photosensitizer.
AB  - Logical progress: Independent molecular logic gates have been designed and
      characterized. Then, the individual molecular logic gates were coerced to work
      together within a micelle. Information relay between the two logic gates was
      achieved through the intermediacy of singlet oxygen. Working together, these
      concatenated logic gates result in a self-reporting and activatable
      photosensitizer. GSH=glutathione. 

PMID- 24030975
TI  - Outcomes of percutaneous coronary intervention of chronic total saphenous vein
      graft occlusions in the contemporary era.
AB  - BACKGROUND: Percutaneous coronary intervention of a chronic total occlusion to a
      saphenous vein graft is currently not recommended because the benefit/risk ratio
      is considered unfavorable. However, there is a patient subset with clinical
      ischemia, and PCI of the native chronic total occlusion (CTO) is unfavorable. In
      this setting, PCI to the saphenous vein graft (SVG) may have utility. We reviewed
      our experience to determine its value in the modern era. METHODS AND RESULTS:
      This was a single-center retrospective study of all patients undergoing PCI to
      SVG CTO. Of 161 patients undergoing SVG PCI during the study period, 27 patients
      underwent 28 SVG CTO PCI, which was technically successful in 79% (22/28). There
      were 2 intra-procedural Q wave myocardial infarctions. At 30 days there were no
      adverse events after hospital discharge. Angina relief was significantly better
      at 30 days in successful (n = 21) vs. unsuccessful (n = 6) PCI(90% vs. 33% P <
      0.01). At the last available follow-up (591 +/- 407 days), angina improvement
      persisted (80.1% vs. 33%, P < 0.01). Long-term adverse events were not
      significantly different between the two groups. CONCLUSION: PCI to SVG CTO is
      feasible with a reasonable success rate, safety profile, and improvement in
      angina in contemporary practice. This approach may be considered in highly
      selected patients where revascularization to the ischemic territory is
      appropriate and the native CTO is technically difficult to recanalize.

PMID- 24030976
TI  - MYC phosphorylation at novel regulatory regions suppresses transforming activity.
AB  - Despite its central role in human cancer, MYC deregulation is insufficient by
      itself to transform cells. Because inherent mechanisms of neoplastic control
      prevent precancerous lesions from becoming fully malignant, identifying
      transforming alleles of MYC that bypass such controls may provide fundamental
      insights into tumorigenesis. To date, the only activated allele of MYC known is
      T58A, the study of which led to identification of the tumor suppressor FBXW7 and
      its regulator USP28 as a novel therapeutic target. In this study, we screened a
      panel of MYC phosphorylation mutants for their ability to promote anchorage
      independent colony growth of human MCF10A mammary epithelial cells, identifying
      S71A/S81A and T343A/S344A/S347A/S348A as more potent oncogenic mutants compared
      with wild-type (WT) MYC. The increased cell-transforming activity of these
      mutants was confirmed in SH-EP neuroblastoma cells and in three-dimensional
      MCF10A acini. Mechanistic investigations initiated by a genome-wide mRNA
      expression analysis of MCF10A acini identified 158 genes regulated by the mutant
      MYC alleles, compared with only 112 genes regulated by both WT and mutant
      alleles. Transcriptional gain-of-function was a common feature of the mutant
      alleles, with many additional genes uniquely dysregulated by individual mutant.
      Our work identifies novel sites of negative regulation in MYC and thus new sites
      for its therapeutic attack.

PMID- 24030978
TI  - Antitumor efficacy of a monoclonal antibody that inhibits the activity of cancer
      associated carbonic anhydrase XII.
AB  - Carbonic anhydrase XII (CA XII) is a membrane-tethered cell surface enzyme that
      is highly expressed on many human tumor cells. Carbonic anhydrase members in this
      class of exofacial molecules facilitate tumor metabolism by facilitating CO2
      venting and intracellular pH regulation. Accordingly, inhibition of exofacial CAs
      has been proposed as a general therapeutic strategy to target cancer. The recent
      characterization of 6A10, the first CA XII-specific inhibitory monoclonal
      antibody, offered an opportunity to evaluate this strategy with regard to CA XII
      mediated catalysis. Using functional assays, we showed that 6A10 inhibited
      exofacial CA activity in CA XII-expressing cancer cells. 6A10 reduced spheroid
      growth in vitro under culture conditions where CA XII was active (i.e., alkaline
      pH) and where its catalytic activity was likely rate-limiting (i.e., restricted
      extracellular HCO3-supply). These in vitro results argued that the antibody
      exerted its growth-retarding effect by acting on the catalytic process, rather
      than on antigen binding per se. Notably, when administered in a mouse xenograft
      model of human cancer, 6A10 exerted a significant delay on tumor outgrowth. These
      results corroborate the notion that exofacial CA is critical for cancer cell
      physiology and they establish the immunotherapeutic efficacy of targeting CA XII
      using an inhibitory antibody.

PMID- 24030977
TI  - GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid
      cells through interleukin-4 receptor-alpha.
AB  - Malignant gliomas are lethal cancers in the brain and heavily infiltrated by
      myeloid cells. Interleukin-4 receptor-alpha (IL-4Ralpha) mediates the
      immunosuppressive functions of myeloid cells, and polymorphisms in the IL-4Ralpha
      gene are associated with altered glioma risk and prognosis. In this study, we
      sought to evaluate a hypothesized causal role for IL-4Ralpha and myeloid
      suppressor cells in glioma development. In both mouse de novo gliomas and human
      glioblastoma cases, IL-4Ralpha was upregulated on glioma-infiltrating myeloid
      cells but not in the periphery or in normal brain. Mice genetically deficient for
      IL-4Ralpha exhibited a slower growth of glioma associated with reduced production
      in the glioma microenvironment of arginase, a marker of myeloid suppressor cells,
      which is critical for their T-cell inhibitory function. Supporting this result,
      investigations using bone marrow-derived myeloid cells showed that IL-4Ralpha
      mediates IL-13-induced production of arginase. Furthermore, glioma-derived
      myeloid cells suppressed T-cell proliferation in an IL-4Ralpha-dependent manner,
      consistent with their identification as myeloid-derived suppressor cells (MDSC).
      Granulocyte macrophage colony-stimulating factor (GM-CSF) plays a central role
      for the induction of IL-4Ralpha expression on myeloid cells, and we found that GM
      CSF is upregulated in both human and mouse glioma microenvironments compared with
      normal brain or peripheral blood samples. Together, our findings establish a GM
      CSF-induced mechanism of immunosuppression in the glioma microenvironment via
      upregulation of IL-4Ralpha on MDSCs.

PMID- 24030979
TI  - Substance P autocrine signaling contributes to persistent HER2 activation that
      drives malignant progression and drug resistance in breast cancer.
AB  - ERBB receptor transmodulation by heterologous G-protein-coupled receptors (GPCR)
      generates functional diversity in signal transduction. Tachykinins are
      neuropeptides and proinflammatory cytokines that promote cell survival and cancer
      progression by activating several GPCRs. In this work, we found that the pain
      associated tachykinin Substance P (SP) contributes to persistent transmodulation
      of the ERBB receptors, EGFR and HER2, in breast cancer, acting to enhance
      malignancy and therapeutic resistance. SP and its high-affinity receptor NK-1R
      were highly expressed in HER2(+) primary breast tumors (relative to the luminal
      and triple-negative subtypes) and were overall correlated with poor prognosis
      factors. In breast cancer cell lines and primary cultures derived from breast
      cancer samples, we found that SP could activate HER2. Conversely, RNA
      interference-mediated attenuation of NK-1R, or its chemical inhibition, or
      suppression of overall GPCR-mediated signaling, all strongly decreased steady
      state expression of EGFR and HER2, establishing that their basal activity relied
      upon transdirectional activation by GPCR. Thus, SP exposure affected cellular
      responses to anti-ERBB therapies. Our work reveals an important oncogenic
      cooperation between NK-1R and HER2, thereby adding a novel link between
      inflammation and cancer progression that may be targetable by SP antagonists that
      have been clinically explored.

PMID- 24030980
TI  - New discoveries of old SON: a link between RNA splicing and cancer.
AB  - The SON protein is a ubiquitously expressed DNA- and RNA-binding protein
      primarily localized to nuclear speckles. Although several early studies
      implicated SON in DNA-binding, tumorigenesis and apoptosis, functional
      significance of this protein had not been recognized until recent studies
      discovered SON as a novel RNA splicing co-factor. During constitutive RNA
      splicing, SON ensures efficient intron removal from the transcripts containing
      suboptimal splice sites. Importantly, SON-mediated splicing is required for
      proper processing of selective transcripts related to cell cycle, microtubules,
      centrosome maintenance, and genome stability. Moreover, SON regulates alternative
      splicing of RNAs from the genes involved in apoptosis and epigenetic
      modification. In addition to the role in RNA splicing, SON has an ability to
      suppress transcriptional activation at certain promoter/enhancer DNA sequences.
      Considering the multiple SON target genes which are directly involved in cell
      proliferation, genome stability and chromatin modifications, SON is an emerging
      player in gene regulation during cancer development and progression. Here, we
      summarize available information from several early studies on SON, and highlight
      recent discoveries describing molecular mechanisms of SON-mediated gene
      regulation. We propose that our future effort on better understanding of diverse
      SON functions would reveal novel targets for cancer therapy.

PMID- 24030981
TI  - Proteomic analysis reveals important role of 14-3-3sigma in anoikis resistance of
      cholangiocarcinoma cells.
AB  - Cholangiocarcinoma (CCA), a high-prevalence cancer in Thailand, is highly
      metastatic and has high mortality rates. Anoikis resistance or the ability of
      cells to survive after detachment from extracellular matrix is a necessary
      property of metastatic cancer. Here, we report differential protein expression of
      an anoikis-resistant CCA cell line culture, under attachment conditions compared
      to nonattachment conditions, studied using 2DE coupled with protein
      identification by LC-MS/MS. Our data reveal the deregulation of proteins involved
      in stress response, cytoskeleton rearrangement, proapoptosis, cell proliferation,
      and glycolysis. Interestingly, 14-3-3sigma (14-3-3 sigma) protein was intensely
      upregulated in detached CCA cells. Real-time RT-PCR analysis confirmed that only
      the sigma isotype was the most abundant transcript among 14-3-3 genes in CCA
      cells. Furthermore, silencing 14-3-3sigma expression by small interfering RNA in
      CCA cells resulted in significantly increased percentage of cell death in
      detached culture. Our findings provide the first evidence showing that 14-3
      3sigma protein plays a crucial role in anoikis resistance of CCA cells.
      Therefore, 14-3-3sigma might be a potential target in CCA therapy. 

PMID- 24030982
TI  - On-site formation of emulsions by controlled air plugs.
AB  - Air plugs are usually undesirable in microfluidic systems because of their
      detrimental effect on the system's stability and integrity. By controlling the
      wetting properties as well as the topographical geometry of the microchannel, it
      is reported herein that air plugs can be generated in pre-defined locations to
      function as a unique valve, allowing for the on-site formation of various
      emulsions including single-component droplets, composite droplets with droplet-to
      droplet concentration gradient, blood droplets, paired droplets, as well as
      bubble arrays without the need for precious flow control, a difficult task with
      conventional droplet microfluidics. Moreover, the self-generated air valve can be
      readily deactivated (turned off) by the introduction of an oil phase, allowing
      for the on-demand release of as-formed droplets for downstream applications. It
      is proposed that the simple, yet versatile nature of this technique can act as an
      important method for droplet microfluidics and, in particular, is ideal for the
      development of affordable lab-on-a-chip systems without suffering from
      scalability and manufacturing challenges that typically confound the conventional
      droplet microfluidics. 

PMID- 24030983
TI  - Multitreatment comparison meta-analysis: promise and peril.

PMID- 24030984
TI  - Varenicline and combination nicotine replacement therapy are the most effective
      pharmacotherapies for treating tobacco use.

PMID- 24030985
TI  - DNA vs. mirror-image DNA: a universal approach to tune the absolute configuration
      in DNA-based asymmetric catalysis.
AB  - Mirror mirror on the wall: By taking advantage of the unique structural features
      of L-DNA, the first examples of left-helical enantioselective induction in the
      field of DNA-based asymmetric catalysis were realized. Most importantly, this
      approach is the only one that allows a reliable and predictable access to both
      enantiomers for any given reaction. 

PMID- 24030986
TI  - Translating antibody insights.

PMID- 24030991
TI  - Planetary science. It's official--Voyager has left the solar system.

PMID- 24030992
TI  - Climate science. Researchers wary as DOE bids to build sixth U.S. climate model.

PMID- 24030993
TI  - Space science. Novel craft sets out to probe the mysteries of moondust.

PMID- 24030994
TI  - Genomics. Researchers to explore promise, risks of sequencing newborns' DNA.

PMID- 24030995
TI  - Alarm over autism test.

PMID- 24030996
TI  - Immunology. Bound for glory.

PMID- 24030997
TI  - Immunology. A once-in-a-lifetime flu shot?

PMID- 24030998
TI  - Turkey's biodiversity funding on the rise.

PMID- 24030999
TI  - Waiving concerns about conflicts of interest.

PMID- 24031000
TI  - Waiving concerns about conflicts of interest--response.

PMID- 24031002
TI  - Comment on "Influence of HLA-C expression level on HIV control".
AB  - Apps et al. (Reports, 5 April 2013, p. 87) found that high human leukocyte
      antigen C (HLA-C) expression favors HIV-1 control. However, as noted here, HLA-C
      was assessed with a monoclonal antibody (DT9) that cross-reacts with HLA-E. In
      the context of the available evidence, this is consistent with the idea that the
      two leukocyte antigens collaborate to keep the HIV-1 virus at bay. 

PMID- 24031003
TI  - Response to Comment on "Influence of HLA-C expression level on HIV control".
AB  - Lo Monaco et al. propose that human leukocyte antigen E (HLA-E) and HLA-C
      expression levels both contribute to HIV control. The minimal, flat level of cell
      surface HLA-E detectable by staining with available HLA-E-specific antibodies
      questions a role for differential HLA-E expression in determining HIV control.
      Evidence remains far stronger that HLA-C expression levels as detected by the DT9
      antibody specifically affect HIV control. 

PMID- 24031004
TI  - Public health. DNA identification after conflict or disaster.

PMID- 24031005
TI  - Materials science. Toward lighter, stiffer materials.

PMID- 24031006
TI  - Immunology. Sensing endotoxins from within.

PMID- 24031007
TI  - Physics. Opportunities knock with a more stable optical clock.

PMID- 24031008
TI  - Cancer. Circulating tumor cells.

PMID- 24031009
TI  - Physics. Cold atom cosmology.

PMID- 24031010
TI  - Antibodies. The future is now. Introduction.

PMID- 24031011
TI  - Antibody therapeutics in cancer.
AB  - In a relatively short period of time, monoclonal antibodies have entered the
      mainstream of cancer therapy. Their first use was as antagonists of oncogenic
      receptor tyrosine kinases, but today monoclonal antibodies have emerged as long
      sought vehicles for the targeted delivery of potent chemotherapeutic agents and
      as powerful tools to manipulate anticancer immune responses. With ever more
      promising results from the clinic, the future will likely see continued growth in
      the discovery and development of therapeutic antibodies and their derivatives. 

PMID- 24031013
TI  - Diversity among memory B cells: origin, consequences, and utility.
AB  - Immunological memory is the residuum of a successful immune response that in the
      B cell lineage comprises long-lived plasma cells and long-lived memory B cells.
      It is apparent that distinct classes of memory B cells exist, distinguishable by,
      among other things, immunoglobulin isotype, location, and passage through the
      germinal center. Some of this variation is due to the nature of the antigen, and
      some appears to be inherent to the process of forming memory. Here, we consider
      the heterogeneity in development and phenotype of memory B cells and whether
      particular functions are partitioned into distinct subsets. We consider also how
      understanding the details of generating memory may provide opportunities to
      develop better, functionally targeted vaccines. 

PMID- 24031014
TI  - Organotextile catalysis.
AB  - Throughout human history, textiles have been integral to daily life, but their
      exploration in catalysis has been rare. Herein, we show a facile and permanent
      immobilization of organocatalysts on the textile nylon using ultraviolet light.
      The catalyst and the textile material require no chemical modification for the
      immobilization. All of the prepared textile-immobilized organocatalysts (a Lewis
      basic, a Bronsted acidic, and a chiral organocatalyst) display excellent
      stability, activity, and recyclability for various organic transformations. Very
      good enantioselectivity (>95:5 enantiomeric ratio) can be maintained for more
      than 250 cycles of asymmetric catalysis. Practical and straightforward
      applications of textile organocatalysis may be beneficial for various fields by
      offering inexpensive and accessible functionalized catalytic materials. 

PMID- 24031012
TI  - Antibodies in HIV-1 vaccine development and therapy.
AB  - Despite 30 years of study, there is no HIV-1 vaccine and, until recently, there
      was little hope for a protective immunization. Renewed optimism in this area of
      research comes in part from the results of a recent vaccine trial and the use of
      single-cell antibody-cloning techniques that uncovered naturally arising, broad
      and potent HIV-1-neutralizing antibodies (bNAbs). These antibodies can protect
      against infection and suppress established HIV-1 infection in animal models. The
      finding that these antibodies develop in a fraction of infected individuals
      supports the idea that new approaches to vaccination might be developed by
      adapting the natural immune strategies or by structure-based immunogen design.
      Moreover, the success of passive immunotherapy in small-animal models suggests
      that bNAbs may become a valuable addition to the armamentarium of drugs that work
      against HIV-1. 

PMID- 24031015
TI  - HONO emissions from soil bacteria as a major source of atmospheric reactive
      nitrogen.
AB  - Abiotic release of nitrous acid (HONO) in equilibrium with soil nitrite (NO2(-))
      was suggested as an important contributor to the missing source of atmospheric
      HONO and hydroxyl radicals (OH). The role of total soil-derived HONO in the
      biogeochemical and atmospheric nitrogen cycles, however, has remained unknown. In
      laboratory experiments, we found that for nonacidic soils from arid and arable
      areas, reactive nitrogen emitted as HONO is comparable with emissions of nitric
      oxide (NO). We show that ammonia-oxidizing bacteria can directly release HONO in
      quantities larger than expected from the acid-base and Henry's law equilibria of
      the aqueous phase in soil. This component of the nitrogen cycle constitutes an
      additional loss term for fixed nitrogen in soils and a source for reactive
      nitrogen in the atmosphere. 

PMID- 24031016
TI  - Channelized ice melting in the ocean boundary layer beneath Pine Island Glacier,
      Antarctica.
AB  - Ice shelves play a key role in the mass balance of the Antarctic ice sheets by
      buttressing their seaward-flowing outlet glaciers; however, they are exposed to
      the underlying ocean and may weaken if ocean thermal forcing increases. An
      expedition to the ice shelf of the remote Pine Island Glacier, a major outlet of
      the West Antarctic Ice Sheet that has rapidly thinned and accelerated in recent
      decades, has been completed. Observations from geophysical surveys and long-term
      oceanographic instruments deployed down bore holes into the ocean cavity reveal a
      buoyancy-driven boundary layer within a basal channel that melts the channel apex
      by 0.06 meter per day, with near-zero melt rates along the flanks of the channel.
      A complex pattern of such channels is visible throughout the Pine Island Glacier
      shelf. 

PMID- 24031017
TI  - Marine taxa track local climate velocities.
AB  - Organisms are expected to adapt or move in response to climate change, but
      observed distribution shifts span a wide range of directions and rates.
      Explanations often emphasize biological distinctions among species, but general
      mechanisms have been elusive. We tested an alternative hypothesis: that
      differences in climate velocity-the rate and direction that climate shifts across
      the landscape-can explain observed species shifts. We compiled a database of
      coastal surveys around North America from 1968 to 2011, sampling 128 million
      individuals across 360 marine taxa. Climate velocity explained the magnitude and
      direction of shifts in latitude and depth much more effectively than did species
      characteristics. Our results demonstrate that marine species shift at different
      rates and directions because they closely track the complex mosaic of local
      climate velocities. 

PMID- 24031019
TI  - Interacting gears synchronize propulsive leg movements in a jumping insect.
AB  - Gears are found rarely in animals and have never been reported to intermesh and
      rotate functionally like mechanical gears. We now demonstrate functional gears in
      the ballistic jumping movements of the flightless planthopper insect Issus. The
      nymphs, but not adults, have a row of cuticular gear (cog) teeth around the
      curved medial surfaces of their two hindleg trochantera. The gear teeth on one
      trochanter engaged with and sequentially moved past those on the other trochanter
      during the preparatory cocking and the propulsive phases of jumping. Close
      registration between the gears ensured that both hindlegs moved at the same
      angular velocities to propel the body without yaw rotation. At the final molt to
      adulthood, this synchronization mechanism is jettisoned. 

PMID- 24031018
TI  - Cytoplasmic LPS activates caspase-11: implications in TLR4-independent endotoxic
      shock.
AB  - Inflammatory caspases, such as caspase-1 and -11, mediate innate immune detection
      of pathogens. Caspase-11 induces pyroptosis, a form of programmed cell death, and
      specifically defends against bacterial pathogens that invade the cytosol. During
      endotoxemia, however, excessive caspase-11 activation causes shock. We report
      that contamination of the cytoplasm by lipopolysaccharide (LPS) is the signal
      that triggers caspase-11 activation in mice. Specifically, caspase-11 responds to
      penta- and hexa-acylated lipid A, whereas tetra-acylated lipid A is not detected,
      providing a mechanism of evasion for cytosol-invasive Francisella. Priming the
      caspase-11 pathway in vivo resulted in extreme sensitivity to subsequent LPS
      challenge in both wild-type and Tlr4-deficient mice, whereas Casp11-deficient
      mice were relatively resistant. Together, our data reveal a new pathway for
      detecting cytoplasmic LPS. 

PMID- 24031020
TI  - Quantifying the influence of climate on human conflict.
AB  - A rapidly growing body of research examines whether human conflict can be
      affected by climatic changes. Drawing from archaeology, criminology, economics,
      geography, history, political science, and psychology, we assemble and analyze
      the 60 most rigorous quantitative studies and document, for the first time, a
      striking convergence of results. We find strong causal evidence linking climatic
      events to human conflict across a range of spatial and temporal scales and across
      all major regions of the world. The magnitude of climate's influence is
      substantial: for each one standard deviation (1sigma) change in climate toward
      warmer temperatures or more extreme rainfall, median estimates indicate that the
      frequency of interpersonal violence rises 4% and the frequency of intergroup
      conflict rises 14%. Because locations throughout the inhabited world are expected
      to warm 2sigma to 4sigma by 2050, amplified rates of human conflict could
      represent a large and critical impact of anthropogenic climate change. 

PMID- 24031021
TI  - Partial failure of a perforator free flap can be salvaged by a second perforator
      free flap.
AB  - INTRODUCTION: Perforator flaps as an innovative method for soft tissue transfer
      that maximizes function preservation, were originally introduced primarily as
      free flaps. Their reliability and versatility has been found to not differ from
      other sources of free flaps where total failure is an uncommon event. Partial
      failure should also be recognized as a possible dilemma that is perhaps more of a
      unique untoward sequela of perforator flaps. METHOD: A retrospective review of
      our flap experience over the past decade included 310 perforator free flaps.
      Partial perforator flap failure that required a second free flap for salvage was
      selected in 6 patients. RESULTS: All perforator free flaps in our experience that
      had some form of partial failure were anterolateral thigh [ALT] free flaps.
      Clinically initially unrecognizable but ultimately distal flap ischemia could be
      attributed to poor flap design, and was the cause of immediate partial flap
      necrosis in 2 cases. Delayed difficulties were complications not specific to
      perforator flaps. In all cases, a free flap was considered the best option, and a
      second perforator free flap proved to resolve all reconstructive objectives.
      CONCLUSIONS: The root cause of partial failure of a perforator free flap was
      found to be either iatrogenic or de novo in origin. The proper design requires an
      awareness of the correct topographic axis and an understanding of the perforasome
      concept to better insure adequate flap perfusion. If a free flap is still
      considered the best solution after a partial failure, the advantages and benefit
      of a second perforator free flap should not be overlooked.

PMID- 24031022
TI  - HPMA copolymer conjugates of DOX and mitomycin C for combination therapy:
      physicochemical characterization, cytotoxic effects, combination index analysis,
      and anti-tumor efficacy.
AB  - The synthesis, characterization and results of evaluation of the biological
      behavior of HPMA copolymer conjugates bearing anti-cancer drugs doxorubicin and
      mitomycin C are described. Two HPMA copolymer carrier types were synthesized: the
      linear copolymer and the biodegradable high-molecular-weight diblock copolymer
      containing a degradable disulfide bond. The polymer-drug conjugates incubated in
      buffers modeling the intracellular environment released the drugs more rapidly
      than those incubated in bloodstream conditions. Significant in vitro and in vivo
      antitumor synergistic activity of the conjugates in the treatment of EL-4 T-cell
      demonstrates their high potential for solid tumor treatment. 

PMID- 24031023
TI  - Fluorescence lifetime imaging and FRET-induced intracellular redistribution of
      Tat-conjugated quantum dot nanoparticles through interaction with a
      phthalocyanine photosensitiser.
AB  - The interaction of Tat-conjugated PEGylated CdSe/ZnS quantum dots (QD) with the
      amphiphilic disulfonated aluminium phthalocyanine photosensitiser is investigated
      in aqueous solution and in a human breast cancer cell line. In aqueous solution,
      the QDs and phthalocyanine form stable nanocomposites. Using steady-state and
      time-resolved fluorescence measurements combined with singlet oxygen detection,
      efficient Forster resonance energy transfer (FRET) is observed with the QDs
      acting as donors, and the phthalocyanine photosensitiser, which mediates
      production of singlet oxygen, as acceptors. In cells, the Tat-conjugated QDs
      localise in lysosomes and the QD fluorescence lifetimes are close to values
      observed in aqueous solution. Strong FRET-induced quenching of the QD lifetime is
      observed in cells incubated with the nanocomposites using fluorescence lifetime
      imaging microscopy (FLIM). Using excitation of the QDs at wavelengths where
      phthalocyanine absorption is negligible, FRET-induced release of QDs from
      endo/lysosomes is confirmed using confocal imaging and FLIM, which is attributed
      to photooxidative damage to the endo/lysosomal membranes mediated by the
      phthalocyanine acceptor. 

PMID- 24031024
TI  - Tunable ionic transport control inside a bio-inspired constructive bi-channel
      nanofluidic device.
AB  - Inspired by the cooperative functions of the asymmetrical ion channels in living
      cells, a constructive bi-channel nanofluidic device that demonstrates the
      enhanced capability of multiple regulations over both the ion flux amount and the
      ionic rectification property is prepared. In this bi-channel system, the
      construction routes of the two asymmetric conical nanochannels provide a way to
      efficiently transform the nanodevice into four different functional working
      modes. In addition, the variation of external pH conditions leads the nanodevice
      to the uncharged, semi-charged and charged states, where the multistory ionic
      regulating function property is enhanced by the charged degree. This intelligent
      integration of the single functional nanochannels demonstrates a promising future
      for building more functional multi-channel integrated nanodevices as well as
      expands the functionalities of the bio-inspired smart nanochannels. 

PMID- 24031025
TI  - Improved long-term clinical outcomes in patients with ST-elevation myocardial
      infarction undergoing remote ischaemic conditioning as an adjunct to primary
      percutaneous coronary intervention.
AB  - AIMS: Remote ischaemic conditioning as an adjunct to primary percutaneous
      coronary intervention in patients with ST-elevation myocardial infarction
      increases myocardial salvage. We investigated the effect of remote ischaemic
      conditioning on long-term clinical outcome. METHODS AND RESULTS: From February
      2007 to November 2008, 333 patients with a suspected first acute ST-elevation
      myocardial infarction were randomized to receive primary percutaneous coronary
      intervention with (n = 166) or without (n = 167) remote ischaemic conditioning
      (intermittent arm ischaemia through four cycles of 5-min inflation followed by 5
      min deflation of a blood-pressure cuff). Patient follow-up extended from the
      randomization date until an outcome, emigration or January 2012 (median follow-up
      = 3.8 years). The primary endpoint was major adverse cardiac and cerebrovascular
      events (MACCE)-a composite of all-cause mortality, myocardial infarction,
      readmission for heart failure, and ischaemic stroke/transient ischaemic attack.
      The individual components of the primary endpoint comprised the secondary
      endpoints. Outcomes were obtained from Danish nationwide medical registries and
      validated by medical record review and contact to patients' general practitioner.
      In the per-protocol analysis of 251 patient fulfilling trial criteria, MACCE
      occurred for 17 (13.5%) patients in the intervention group compared with 32
      (25.6%) patients in the control group, yielding a hazard ratio (HR) of 0.49 (95%
      confidence interval: 0.27-0.89, P = 0.018). The HR for all-cause mortality was
      0.32 (95% confidence interval: 0.12-0.88, P = 0.027). Although lower precision,
      the HRs were also directionally lower for all other secondary endpoints.
      CONCLUSION: Remote ischaemic conditioning before primary percutaneous coronary
      intervention seemed to improve long-term clinical outcomes in patients with ST
      elevation myocardial infarction.

PMID- 24031026
TI  - Targeting of magnolin on ERKs inhibits Ras/ERKs/RSK2-signaling-mediated
      neoplastic cell transformation.
AB  - Mitogen-activated protein kinases play a key role in cell proliferation, cell
      cycle progression and cell transformation, and activated Ras/extracellular signal
      regulated kinases (ERKs)/ribosomal S6 kinase 2 (RSK2) signaling pathways have
      been widely identified in many solid tumors. In this study, we found that
      magnolin, a compound found in the Magnolia species, directly targeted and
      inhibited ERK1 and ERK2 kinase activities with IC50 values of 87 and 16.5 nM by
      competing with adenosine triphosphate in an active pocket. Further, we
      demonstrated that magnolin inhibited epidermal growth factor (EGF)-induced
      p90RSKs phosphorylation at Thr359/Ser363, but not ERKs phosphorylation at
      Thr202/Tyr204, and this resulted in inhibition of cell proliferation by
      suppression of the G1/S cell cycle transition. Additionally, p38 kinases, Jun N
      terminal kinases and Akts were not involved in the magnolin-mediated inhibitory
      signaling. Magnolin targeting of ERK1 and 2 activities suppressed the
      phosphorylation of RSK2 and downstream target proteins including ATF1 and c-Jun
      and AP-1, a dimer of Jun/Fos, and the transactivation activities of ATF1 and AP
      1. Notably, ERKs inhibition by magnolin suppressed EGF-induced anchorage
      independent cell transformation and colony growth of Ras(G12V)-harboring A549
      human lung cancer cells and NIH3T3 cells stably expressing Ras(G12V) in soft
      agar. Taken together, these results demonstrated that magnolin might be a
      naturally occurring chemoprevention and therapeutic agent capable of inhibiting
      cell proliferation and transformation by targeting ERK1 and ERK2. 

PMID- 24031027
TI  - PD-1 blockage delays murine squamous cell carcinoma development.
AB  - Engagement of programmed death-1 (PD-1) with its two ligands [programmed death
      ligand-1 (PD-L1) and PD-L2] has been associated with the suppression of tumor
      reactive T cells; however, the underlying mechanism for this T-cell dysfunction
      is not clear. We hypothesized that PD-1 and PD-L1 signals are, in part,
      responsible for squamous cell carcinoma (SCC) escape from immune antitumor
      regulation by modulation of the tumor environment. In the present study, we used
      a multistage model of SCC to examine the role of PD-1/PD-L1 activation during
      tumor development. Tumor sites presented an increased percentage of CD4(+) and
      CD8(+) T cells expressing PD-1 when compared with non-tumorigenic control mice,
      whereas the expression of PD-L1 was particularly increased in F4/80(+)
      macrophages in tumor sites. Further, the systemic immune neutralization of PD-1
      resulted in a decreased number and delayed incidence rate of papillomas followed
      by a differential expression of cytokeratins, suggesting that the PD-1-PD-L1
      interaction contributes to the progression of SCC by downregulation of antitumor
      responses. In fact, blocking PD-1 increased the percentage of CD8(+) and CD4(+) T
      cells, and the levels of interferon-gamma in the tumor sites. Our results
      indicated involvement of PD-1(+) T cells in SCC development and in the modulation
      of the inflammatory immune response. 

PMID- 24031028
TI  - SOCS2 mediates the cross talk between androgen and growth hormone signaling in
      prostate cancer.
AB  - Anabolic signals such as androgens and the growth hormone/insulin-like growth
      factor 1 (GH/IGF-1) axis play an essential role in the normal development of the
      prostate but also in its malignant transformation. In this study, we investigated
      the role of suppressor of cytokine signaling 2 (SOCS2) as mediator of the cross
      talk between androgens and GH signals in the prostate and its potential role as
      tumor suppressor in prostate cancer (PCa). We observed that SOCS2 protein levels
      assayed by immunohistochemistry are elevated in hormone therapy-naive localized
      prostatic adenocarcinoma in comparison with benign tissue. In contrast, however,
      castration-resistant bone metastases exhibit reduced levels of SOCS2 in
      comparison with localized or hormone naive, untreated metastatic tumors. In PCa
      cells, SOCS2 expression is induced by androgens through a mechanism that requires
      signal transducer and activator of transcription 5 protein (STAT5) and androgen
      receptor-dependent transcription. Consequentially, SOCS2 inhibits GH activation
      of Janus kinase 2, Src and STAT5 as well as both cell invasion and cell
      proliferation in vitro. In vivo, SOCS2 limits proliferation and production of IGF
      1 in the prostate in response to GH. Our results suggest that the use of GH
      signaling inhibitors could be of value as a complementary treatment for
      castration-resistant PCa. SUMMARY: Androgen induced SOCS2 ubiquitin ligase
      expression and inhibited GH signaling as well as cell proliferation and invasion
      in PCa, whereas reduced SOCS2 was present in castration-resistant cases. GH
      signaling inhibitors might be a complementary therapeutic option for advanced
      PCa.

PMID- 24031029
TI  - External quality assurance with dried tube specimens (DTS) for point-of-care
      syphilis and HIV tests: experience in an indigenous populations screening
      programme in the Brazilian Amazon.
AB  - OBJECTIVES: The availability of point-of-care (POC) tests for infectious diseases
      has revolutionised the provision of healthcare for remote rural populations
      without access to laboratories. However, quality assurance for POC tests has been
      largely overlooked. We have evaluated the use and stability of dry tube specimens
      (DTS) for External Quality Assurance (EQA) for HIV and syphilis screening in
      remote indigenous populations in the Amazon region of Brazil. METHODS: All
      healthcare workers (HCWs) participating in the community-screening were trained.
      We used HIV and syphilis DTS panels developed by the reference laboratory,
      containing samples with negative and positive results at different antibody
      concentrations, for both infections. DTS panels were distributed to HCWs in the
      communities for reconstitution and testing using POC HIV and syphilis tests. The
      results of testing were sent to the reference laboratory for marking and remedial
      action taken where necessary. RESULTS: In total 268 HCWs tested 1607 samples for
      syphilis and 1608 samples for HIV. Results from HCWs showed a concordance rate of
      90% for syphilis and 93% for HIV (kappa coefficients of 0.74 and 0.78,
      respectively) with reference laboratories. Most false negatives were in samples
      of very low antibody concentration. DTS syphilis specimens produced the expected
      results after storage at 2-8 degrees C or at 18-24 degrees C for up to 3 weeks.
      CONCLUSIONS: The results show that POC tests for syphilis and HIV give valid
      results in environments where traditional tests do not work, but errors in the
      interpretation of POC test results were identified by the EQA programme using
      DTS. EQA using DTS can help to improve the quality of screening programmes using
      POC tests in remote regions.

PMID- 24031030
TI  - DNA detection and seroprevalence of human papillomavirus in a cohort of
      adolescent women.
AB  - OBJECTIVES: Human papillomavirus (HPV) infections are common in adolescent women,
      while the rare cancerous sequelae of HPV infections do not generally occur until
      the 4th or 5th decades of life. This prospective study of a cohort of adolescent
      women was performed to further our knowledge of the natural history of incident
      and prevalent HPV infections. METHODS: Self-vaginal swabs collected from high
      risk, unvaccinated adolescent women in a longitudinal study were analysed for HPV
      DNA. Sera were collected at enrolment and later tested for HPV antibodies.
      Statistical analysis was performed to determine the HPV genotype distribution and
      duration of detection, and to determine rates of seropositivity and
      seroconversion for HPV types represented in the assays. RESULTS: 146 subjects
      (mean enrolment age=15.4 years; mean duration of follow-up=5.8 years) had samples
      adequate for analysis of HPV detection, and 95 of these subjects had paired sera
      available. The cumulative prevalence for high-risk and low-risk HPV types was
      95.9% and 91.1%, respectively. HPV types 6, 11, 16 and 18 (HPV types represented
      in the quadrivalent vaccine) were found at some point in 40.4%, 6.2%, 48% and 24%
      of participants, respectively. Serological data confirmed exposure to these
      vaccine-covered types, as well as to other high-risk HPV types. CONCLUSIONS: In
      this cohort of adolescent women, high- and low-risk HPV types were frequently
      detected, and serological data confirmed exposure in most subjects. The high
      prevalence HPV types represented in the quadrivalent HPV vaccine further support
      vaccination of women at an age well before sexual debut.

PMID- 24031032
TI  - Editorial: metabolic modeling in biotechnology and medical research.
AB  - Metabolic Modeling and Simulation: This special issue of Biotechnology Journal is
      edited by Diethard Mattanovich and Vassily Hatzimanikatis and covers the state-of
      the-art in metabolic modeling, including the major themes of methods in metabolic
      modeling, modeling of human and microbial metabolism, and modeling of
      bioprocesses. 

PMID- 24031039
TI  - Synthesis and pharmacological evaluation of a series of the agomelatine analogues
      as melatonin MT1 /MT2 agonist and 5-HT2C antagonist.
AB  - Agomelatine is a naphthalenic analogue of melatonin that is in clinical use for
      the treatment of major depressive disorders. Interestingly, while agomelatine
      exhibits potent affinity for melatonin receptors, it binds with only moderate
      affinity to the serotonin 5-HT2C receptor. Optimization of agomelatine toward
      this target could further potentiate its clinical efficacy. To explore this
      hypothesis and to access derivatives in which a key point of agomelatine
      metabolism is blocked, a series of naphthalenic derivatives was designed and
      synthesized as novel analogues of agomelatine. Most of the prepared compounds
      exhibited good binding affinity at the melatonin MT1 and MT2 receptor subtypes.
      Two compounds, an acetamide and an acrylamide derivative, exhibited good binding
      affinities at both the human melatonin (MT) receptors and the serotonin 5-HT2C
      receptor subtype, with pKi values of 7.96 and 7.95 against MT1, 7.86 and 8.68
      against MT2, and 6.64 and 6.44 against 5-HT2C, respectively.

PMID- 24031040
TI  - The monitoring of diabetes mellitus.

PMID- 24031041
TI  - Is serum human epididymis protein 4 ready for prime time?
AB  - The National Institute for Health and Clinical Excellence (NICE) guidelines have
      sparked hot debate regarding the role of carbohydrate antigen 125 (CA-125) for
      ovarian cancer (OC) detection. Recent literature and evidence calls into question
      the use of CA-125 in diagnostic algorithms, given the better performance of human
      epididymis protein 4 (HE4) vs. CA-125 to rule OC. This is an important
      consideration since combined measurements are not cost-effective. The quality of
      this evidence is, however, threatened by important gaps related to study design,
      enrolled populations and analytical issues. For instance, despite the clinical
      need to prioritize the evaluation of biomarker performance in early stage
      tumours, sound evidence on this cannot be provided. In addition, results should
      be cautiously interpreted due to wide differences in the type of employed assays
      and in adopted diagnostic thresholds for HE4. Comparability among results
      obtained by different commercially available HE4 assays, together with an
      objective establishment of analytical goals is essential for the optimal clinical
      application of this marker. 

PMID- 24031042
TI  - Smaller HDL particles are associated with absence of obstructive coronary artery
      disease in stable angina pectoris patients.
AB  - BACKGROUND: A research on novel cardiovascular risk factors is mainly focused on
      patients with clinically verified coronary artery disease (CAD), while less is
      known about their presence in symptomatic patients, but without angiographically
      proven occlusion of coronary arteries. The aim of this study was to compare
      plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) size and
      subclasses in stable angina patients with and without significant obstructive
      CAD. METHODS: LDL and HDL subclasses were analysed in 100 stable angina patients
      with >=50% of obstruction and 40 patients with less than 50% of luminal
      narrowing, as assessed by coronary angiography. RESULTS: Patients with <50% of
      obstruction had reduced mean HDL size and higher proportion of small HDL
      particles (P < 0.05). HDL size and proportion of small HDL particles were
      significant and independent predictors of obstructive CAD (P < 0.05,
      respectively). CONCLUSIONS: Stable angina patients with <50% of coronary
      obstruction have more favourable HDL subclasses distribution than patients with
      significant coronary stenosis.

PMID- 24031043
TI  - Cerebral lesions on magnetic resonance imaging correlate with preoperative
      neurological status in neonates undergoing cardiopulmonary bypass surgery.
AB  - OBJECTIVES: To determine the prevalence, spectrum and course of cerebral lesions
      in neonates with congenital heart disease (CHD) undergoing full flow
      cardiopulmonary bypass (CPB) surgery using magnetic resonance imaging (MRI) and
      to examine the correlation between cerebral lesions and clinical neurological
      abnormalities. METHODS: Prospective cohort study of neonates with d-transposition
      of the great arteries (n = 22), univentricular heart malformation with
      hypoplastic aortic arch (n = 6) and aortic arch obstructions (n = 2) undergoing
      CPB. Neonates underwent cerebral MRI and blinded standardized neurological
      examination before (median day 6) and after surgery (day 13). The MRI findings
      were compared with those of 20 healthy controls. RESULTS: Preoperative cerebral
      lesions were present in 7 of 30 patients (23%) with isolated mild or moderate
      white matter injury (WMI) (n = 4), isolated small cerebral stroke (n = 1) and
      combined WMI and stroke (n = 2). None of the healthy controls had cerebral
      lesions on MRI. CHD neonates with preoperative cerebral lesions had more
      neurological abnormalities (P = 0.01) than neonates without cerebral lesions. Low
      arterial oxygen saturation (P = 0.03) was a risk factor for preoperative cerebral
      lesions, while balloon atrioseptostomy (P = 0.19) was not. After surgery,
      preoperative cerebral lesions persisted in 5 of 7 neonates, and 2 neonates (7%)
      showed signs of additional WMI in their postoperative MRI. CONCLUSIONS: In
      neonates with severe CHD, WMI was the predominant preoperative finding, while
      cerebral strokes were less frequent. New postoperative lesions were rare.
      Preoperative neurological abnormalities correlated with the presence of cerebral
      lesions on MRI.

PMID- 24031044
TI  - Results of Li-Tho trial: a prospective randomized study on effectiveness of
      LigaSure(r) in lung resections.
AB  - OBJECTIVE: The role of electro-thermal bipolar tissue sealing system
      (LigaSure((r)), (LS); Covidien, Inc., CO, USA) in thoracic surgery is still
      undefined. Reports of its use are still limited. The objective of the trial was
      to evaluate the cost and benefits of LS in major lung resection surgery. METHODS:
      A randomized blinded study of a consecutive series of 100 patients undergoing
      lobectomy was undertaken. After muscle-sparing thoracotomy and classification of
      lung fissures according to Craig-Walker, patients with fissure Grade 2-4 were
      randomized to Stapler group or LS group fissure completion. Recorded parameters
      were analysed for differences in selected intraoperative and postoperative
      outcomes. Statistical analysis was performed with the bootstrap method. Pearson's
      chi(2) test and Fisher's exact test were used to calculate probability value for
      dichotomous variables comparison. Cost-benefit evaluation was performed using
      Pareto optimal analysis. RESULTS: There were no significant differences between
      groups, regarding demographic and baseline characteristics. No patient was
      withdrawn from the study; no adverse effect was recorded. There was no mortality
      or major complications in both groups. There were no statistically significant
      differences as to operative time or morbidity between patients in the LS group
      compared with the Stapler group. In the LS group, there was a not statistically
      significant increase of postoperative air leaks in the first 24 postoperative
      hours, while a statistically significant increase of drainage amount was observed
      in the LS group. No statistically significant difference in hospital length of
      stay was observed. Overall, the LS group had a favourable multi-criteria analysis
      of cost/benefit ratio with a good 'Pareto optimum'. CONCLUSIONS: LS is a safe
      device for thoracic surgery and can be a valid alternative to Staplers. In this
      setting, LS allows functional lung tissue preservation. As to costs, LS seems
      equivalent to Staplers.

PMID- 24031036
TI  - Predicting complex phenotype-genotype interactions to enable yeast engineering:
      Saccharomyces cerevisiae as a model organism and a cell factory.
AB  - There is an increasing use of systems biology approaches in both "red" and
      "white" biotechnology in order to enable medical, medicinal, and industrial
      applications. The intricate links between genotype and phenotype may be explained
      through the use of the tools developed in systems biology, synthetic biology, and
      evolutionary engineering. Biomedical and biotechnological research are among the
      fields that could benefit most from the elucidation of this complex relationship.
      Researchers have studied fitness extensively to explain the phenotypic impacts of
      genetic variations. This elaborate network of dependencies and relationships so
      revealed are further complicated by the influence of environmental effects that
      present major challenges to our achieving an understanding of the cellular
      mechanisms leading to healthy or diseased phenotypes or optimized production
      yields. An improved comprehension of complex genotype-phenotype interactions and
      their accurate prediction should enable us to more effectively engineer yeast as
      a cell factory and to use it as a living model of human or pathogen cells in
      intelligent screens for new drugs. This review presents different methods and
      approaches undertaken toward improving our understanding and prediction of the
      growth phenotype of the yeast Saccharomyces cerevisiae as both a model and a
      production organism. 

PMID- 24031045
TI  - Double arterial perfusion strategy for extensive thoracic aortic surgery to avoid
      lower body hypothermic circulatory arrest.
AB  - OBJECTIVE: To analyse our results of using a double arterial perfusion strategy
      to avoid lower body hypothermic circulatory arrest after extensive thoracic
      aortic surgery. METHODS: We analysed the intra- and perioperative courses of 10
      patients (median age 58 years, median logistic EuroSCORE 14.6) who underwent
      extensive thoracic aortic surgery with a double arterial perfusion strategy. The
      main goal of double arterial perfusion is to separate myocardial and supra-aortic
      from systemic perfusion. Aortic repair starts at the most distal level of the
      descending aorta, followed by reinsertion of the supra-aortic vessels, and ends
      with completion of the proximal anastomosis or by any kind of root repair as
      needed. RESULTS: Seven of 10 patients had prior surgery of the thoracic aorta.
      Indications for surgery were post-dissection aneurysm in 4 patients, true
      aneurysm in 3, anastomotic aneurysms in 2 and Type B aortic dissection with
      pseudo-coarctation in 1. Surgical access was performed through median sternotomy
      with left hemi-clamshell extension in all cases. There was no in-hospital
      mortality, but perioperative neurological symptoms occurred in 2 patients. These
      2 patients developed delayed stroke (after awaking) after an initial uneventful
      clinical course, and in 1 of them, neurological symptoms resolved completely
      during follow-up. The median follow-up was 7 (+/- 13) months. There was no death
      and no need for additional redo surgery during this observational period.
      CONCLUSIONS: Extensive surgery of the thoracic aorta using a double arterial
      perfusion technique in order to avoid lower body hypothermic circulatory arrest
      is an attractive option. Further refinements of this technique may enable the
      safe and effective simultaneous multisegmental treatment of thoracic aortic
      pathology in patients who would otherwise have to undergo a two-step surgical
      approach.

PMID- 24031046
TI  - Percutaneous radiofrequency sympathicolysis versus surgical standard procedure.

PMID- 24031047
TI  - Long-term survival of non-smokers undergoing coronary artery bypass surgery.
AB  - OBJECTIVES: We sought to investigate long-term survival of non-smokers undergoing
      coronary artery bypass surgery (CABG). METHODS: A prospective database of
      consecutive patients was retrospectively analysed and cross correlated with the
      UK strategic tracking service to evaluate survival after primary CABG.
      Univariate, multivariate and a propensity analyses were performed. RESULTS: We
      analysed 13 337 primary CABG procedures. Median follow-up was 7 years. Kaplan
      Meier survival curves demonstrate that non-smokers have a significantly improved
      long-term survival compared with ex- and current smokers, P < 0.0001. Cox
      regression analysis identified smoking status, age, diabetes, ejection fraction
      (EF), body mass index, cerebrovascular disease, dialysis, left internal mammary
      artery (LIMA) non-usage, postoperative creatinine kinase muscle-brain isoenzyme
      (CKMB), radial artery usage, preoperative rhythm, forced vital capacity (FVC) and
      logistic EuroSCORE as significant risk factors determining long-term survival.
      Propensity matching resulted in 3575 non-smokers being matched 1:1, with ex
      smokers. After matching, univariate analysis demonstrated the significantly worse
      long-term survival of ex-smokers compared with non-smokers, P < 0.0001. Cox
      regression analysis identified smoking status, age, postoperative CKMB,
      cerebrovascular disease, dialysis, diabetes, EF, FVC, LIMA non-usage, radial
      artery used, sinus rhythm and logistic EuroSCORE as significant risk factors
      determining long-term survival. Survival by smoking status plotted at the mean of
      the covariates, prepropensity matching, demonstrated that non-smokers had a
      significantly better long-term survival than ex-smokers, P < 0.0001; however,
      after propensity matching, non-smokers under 65 years of age had a significantly
      worse long-term survival compared with ex-smokers, P < 0.0001. CONCLUSIONS: Non
      smokers under the age of 65 years of age have significantly worse long-term
      survival compared with ex-smokers after risk factor adjustment. We speculate that
      this is because ex-smokers have had the causative factor, smoking, removed, but
      non-smokers have not.

PMID- 24031048
TI  - Progressive decrease of N-acetylaspartate to total creatine ratio in the
      pregenual anterior cingulate cortex in patients with major depressive disorder:
      longitudinal 1H-MR spectroscopy study.
AB  - BACKGROUND: Longitudinal metabolic changes of total choline (tCho),
      creatine+phosphocreatine (total creatine, tCr), and N-acetylaspartate (NAA) in
      the pregenual anterior cingulate cortex (pACC) of patients with major depressive
      disorder (MDD) have not been well evaluated. PURPOSE: To evaluate the
      longitudinal changes of the metabolic levels of tCho, tCr, and NAA in the pACC of
      MDD patients and normal controls with the use of Single-voxel (1)HMRS. MATERIAL
      AND METHODS: Single-voxel (1)HMRS was acquired in the pACC of 21 female patients
      with MDD and 26 age- and gender-matched controls. Follow-up scans were acquired
      in 10 patients with MDD and 15 controls after 9-10 months from baseline scans.
      Absolute concentrations of tCho, tCr, and NAA, and the ratios of NAA/tCr and
      tCho/tCr were calculated and compared between and within groups. RESULTS: The
      patient group showed slightly improved clinical symptoms, as measured by Beck's
      Depression Inventory (P=0.035), after treatment with antidepressants. Comparison
      of baseline scans between the groups showed no differences in any of the absolute
      metabolite concentrations or ratios. The NAA/tCr ratio in the pACC of patients
      with MDD showed a significant decrease in the follow-up scan (P=0.032), and the
      NAA/tCr ratio of the baseline scan showed logarithmic negative association with
      illness duration (P=0.024). CONCLUSION: A progressive decrease in the NAA/tCr
      ratio in the pACC of patients with MDD was demonstrated and the decrease in this
      ratio was at the highest rate in the early period after illness onset. These
      findings indicate the neuronal degeneration and dysfunction of the pACC, and the
      importance of early clinical intervention in female patients with MDD.

PMID- 24031049
TI  - Coronary computed tomography angiography at 140 kV versus 120 kV: assessment of
      image quality and radiation exposure in overweight and moderately obese patients.
AB  - BACKGROUND: Although a tube potential of 140 kV is available on most computed
      tomography (CT) scanners, its incremental diagnostic value versus 120 kV has been
      controversial. PURPOSE: To retrospectively evaluate the image quality and
      radiation exposure of cardiac computed tomography angiography (CCTA) performed at
      140 kV in comparison to CCTA at 120 kV in overweight and moderately obese
      patients. MATERIAL AND METHODS: Eighty-eight patients who were referred for CCTA
      between January 2010 and May 2012 were included. Forty-four patients who were
      overweight or moderately obese (body mass index [BMI], 25-35 kg/m(2)) underwent
      CCTA with dual-source CT (DSCT) scanner at 140 kV. Forty-four match controls who
      underwent CCTA with DSCT at 120 kV were identified per BMI, average heart rate,
      scan indication, and scan acquisition mode. All scans were performed per routine
      protocols with direct physician supervision. Quantitative image metrics (CT
      attenuation, image noise, contrast-to-noise ratio [CNR], and signal-to-noise
      ratio [SNR] of left main [LM] and proximal right coronary artery [RCA]) were
      assessed. Effective radiation dose was compared between the two groups. RESULTS:
      Overall, all scans were diagnostic without any non-evaluable coronary segment per
      clinical report. 140 kV had a lower attenuation and image noise versus 120 kV
      (P<0.01). Both SNR and CNR of proximal coronary arteries were similar between 140
      kV and 120 kV (SNR, LM P=0.93, RCA P=0.62; CNR, LM P=0.57, RCA P=0.77). 140 kV
      was associated with a 35.3% increase in effective radiation dose as compared with
      120 kV (5.1 [3.6-8.2] vs. 3.3 [2.0-5.1] mSv, respectively; P<0.01). CONCLUSION:
      140 kV CCTA resulted in similar image quality but a higher effective radiation
      dose in comparison to 120 kV CCTA. Therefore, in overweight and moderately obese
      patients, a tube potential of 120 kV may be sufficient for CCTA with diagnostic
      image quality.

PMID- 24031050
TI  - Exclusive localization of carbonic anhydrase in bacteriocytes of the deep-sea
      clam Calyptogena okutanii with thioautotrophic symbiotic bacteria.
AB  - Deep-sea Calyptogena clams harbor thioautotrophic intracellular symbiotic
      bacteria in their gill epithelial cells. The symbiont fixes CO2 to synthesize
      organic compounds. Carbonic anhydrase (CA) from the host catalyzes the reaction
      CO2 + H2O <-> HCO3(-) + H(+), and is assumed to facilitate inorganic carbon (Ci)
      uptake and transport to the symbiont. However, the localization of CA in gill
      tissue remains unknown. We therefore analyzed mRNA sequences, proteins and CA
      activity in Calyptogena okutanii using expression sequence tag, SDS-PAGE and LC
      MS/MS. We found that acetazolamide-sensitive soluble CA was abundantly expressed
      in the gill tissue of C. okutanii, and the enzyme was purified by affinity
      chromatography. Mouse monoclonal antibodies against the CA of C. okutanii were
      used in western blot analysis and immunofluorescence staining of the gill tissues
      of C. okutanii, which showed that CA was exclusively localized in the symbiont
      harboring cells (bacteriocytes) in gill epithelial cells. Western blot analysis
      and measurement of activity showed that CA was abundantly (26-72% of total
      soluble protein) detected in the gill tissues of not only Calyptogena clams but
      also deep-sea Bathymodiolus mussels that harbor thioautotrophic or methanotrophic
      symbiotic bacteria, but was not detected in a non-symbiotic mussel, Mytilus sp.
      The present study showed that CA is abundant in the gill tissues of deep-sea
      symbiotic bivalves and specifically localizes in the cytoplasm of bacteriocytes
      of C. okutanii. This indicates that the Ci supply process to symbionts in the
      vacuole (symbiosome) in bacteriocytes is essential for symbiosis. 

PMID- 24031051
TI  - Spectral tuning of Amazon parrot feather coloration by psittacofulvin pigments
      and spongy structures.
AB  - The feathers of Amazon parrots are brightly coloured. They contain a unique class
      of pigments, the psittacofulvins, deposited in both barbs and barbules, causing
      yellow or red coloured feathers. In specific feather areas, spongy nanostructured
      barb cells exist, reflecting either in the blue or blue-green wavelength range.
      The blue-green spongy structures are partly enveloped by a blue-absorbing, yellow
      colouring pigment acting as a spectral filter, thus yielding a green coloured
      barb. Applying reflection and transmission spectroscopy, we characterized the
      Amazons' pigments and spongy structures, and investigated how they contribute to
      the feather coloration. The reflectance spectra of Amazon feathers are presumably
      tuned to the sensitivity spectra of the visual photoreceptors. 

PMID- 24031052
TI  - Eclosion gates progression of the adult ecdysis sequence of Drosophila.
AB  - Animal behavior is often organized into stereotyped sequences that promote the
      goals of reproduction, development and survival. However, for most behaviors, the
      neural mechanisms that govern the order of execution of the motor programs within
      a sequence are poorly understood. An important model in understanding the
      hormonal determinants of behavioral sequencing is the ecdysis sequence, which is
      performed by insects at each developmental transition, or molt. The adult ecdysis
      sequence in Drosophila includes the emergence of the insect from the pupal case
      followed by expansion and hardening of the wings. Wing expansion is governed by
      the hormone bursicon, and stimulation of the bursicon-expressing neurons in newly
      eclosed flies induces rapid wing expansion. Here we show that that such
      stimulation delivered prior to eclosion has no immediate effect, but does cause
      rapid wing expansion after eclosion if the stimulus is delivered within 40 min of
      that event. We observe a similar delayed effect upon stimulation of a single pair
      of bursicon-expressing neurons previously identified as command neurons for wing
      expansion. We conclude that command neuron stimulation enables the motor output
      pathway for wing expansion, but that this pathway is blocked prior to eclosion.
      By manipulating the time of eclosion, we demonstrate that some physiological
      process tightly coupled to adult ecdysis releases the block on wing expansion.
      Eclosion thus serves as a behavioral checkpoint and complements hormonal
      mechanisms to ensure that wing expansion strictly follows eclosion in the ecdysis
      sequence. 

PMID- 24031053
TI  - Post-prandial regulation of hepatic glucokinase and lipogenesis requires the
      activation of TORC1 signalling in rainbow trout (Oncorhynchus mykiss).
AB  - To assess the potential involvement of TORC1 (target of rapamycin complex 1)
      signalling in the regulation of post-prandial hepatic lipid and glucose
      metabolism-related gene expression in trout, we employed intraperitoneal
      administration of rapamycin to achieve an acute inhibition of the TOR pathway.
      Our results reveal that rapamycin inhibits the phosphorylation of TORC1 and its
      downstream effectors (S6K1, S6 and 4E-BP1), without affecting Akt and the Akt
      substrates Forkhead-box Class O1 (FoxO1) and glycogen synthase kinase 3alpha/beta
      (GSK 3alpha/beta). These results indicate that acute administration of rapamycin
      in trout leads to the inhibition of TORC1 activation. No effect is observed on
      the expression of genes involved in gluconeogenesis, glycolysis and fatty acid
      oxidation, but hepatic TORC1 inhibition results in decreased sterol regulatory
      element binding protein 1c (SREBP1c) gene expression and suppressed fatty acid
      synthase (FAS) and glucokinase (GK) at gene expression and activity levels,
      indicating that FAS and GK activity is controlled at a transcriptional level in a
      TORC1-dependent manner. This study demonstrates for the first time in fish that
      post-prandial regulation of hepatic lipogenesis and glucokinase in rainbow trout
      requires the activation of TORC1 signalling. 

PMID- 24031054
TI  - Visual stimulus characteristics that elicit tracking and striking in the praying
      mantises Parasphendale affinis, Popa spurca and Sphodromantis lineola.
AB  - We tested three species of praying mantis, Parasphendale affinis, Popa spurca and
      Sphodromantis lineola, with computer-generated stimuli that differed in size,
      contrast, configuration and movement pattern to determine the effects of these
      parameters on visual tracking and striking behavior. Overall, black disks moving
      erratically against a white background were strong releasers of both behaviors.
      When stimulus presentation order was randomized by size, P. affinis and P. spurca
      struck at progressively higher rates as the stimuli enlarged up to 44 deg; S.
      lineola struck most at intermediate sized (10-20 deg) disks. When disks were size
      ordered from small to large, P. affinis and S. lineola struck at the smaller
      disks at higher rates; however, when the order was reversed, the early appearance
      of large disks suppressed subsequent responses to the smaller disks. Stimulus
      order did not differentially affect the responses of P. spurca. All species
      responded at higher rates to black disks moving against a white background versus
      the reverse. However, only P. spurca and S. lineola responded at higher rates to
      relatively darker grey disks, only P. affinis responded to mottled grey disks
      moving against an identically patterned background, and only P. spurca struck
      more frequently in response to rectangular stimuli oriented parallel (versus
      orthogonal) to their direction of movement. In conjunction with data on other
      species, these results support the hypothesis that praying mantises recognize
      prey based on assessment of several category-specific, spatiotemporal features,
      e.g. size, contrast, speed, movement pattern and leading edge length. 

PMID- 24031055
TI  - Pattern- and contrast-dependent visual response in the box jellyfish Tripedalia
      cystophora.
AB  - Cubomedusae possess a total of 24 eyes, some of which are structurally similar to
      vertebrate eyes. Accordingly, the medusae also display a range of light-guided
      behaviours including obstacle avoidance, diurnal activity patterns and
      navigation. Navigation is supported by spatial resolution and image formation in
      the so-called upper lens eye. Further, there are indications that obstacle
      avoidance requires image information from the lower lens eye. Here we use a
      behavioural assay to examine the obstacle avoidance behaviour of the Caribbean
      cubomedusa Tripedalia cystophora and test whether it requires spatial resolution.
      The possible influence of the contrast and orientation of the obstacles is also
      examined. We show that the medusae can only perform the behaviour when spatial
      information is present, and fail to avoid a uniformly dark wall, directly proving
      the use of spatial vision. We also show that the medusae respond stronger to high
      contrast lines than to low contrast lines in a graded fashion, and propose that
      the medusae use contrast as a semi-reliable measure of distance to the obstacle. 

PMID- 24031056
TI  - Creating a behavioural classification module for acceleration data: using a
      captive surrogate for difficult to observe species.
AB  - Distinguishing specific behavioural modes from data collected by animal-borne tri
      axial accelerometers can be a time-consuming and subjective process. Data
      synthesis can be further inhibited when the tri-axial acceleration data cannot be
      paired with the corresponding behavioural mode through direct observation. Here,
      we explored the use of a tame surrogate (domestic dog) to build a behavioural
      classification module, and then used that module to accurately identify and
      quantify behavioural modes within acceleration collected from other
      individuals/species. Tri-axial acceleration data were recorded from a domestic
      dog whilst it was commanded to walk, run, sit, stand and lie-down. Through video
      synchronisation, each tri-axial acceleration sample was annotated with its
      associated behavioural mode; the feature vectors were extracted and used to build
      the classification module through the application of support vector machines
      (SVMs). This behavioural classification module was then used to identify and
      quantify the same behavioural modes in acceleration collected from a range of
      other species (alligator, badger, cheetah, dingo, echidna, kangaroo and wombat).
      Evaluation of the module performance, using a binary classification system,
      showed there was a high capacity (>90%) for behaviour recognition between
      individuals of the same species. Furthermore, a positive correlation existed
      between SVM capacity and the similarity of the individual's spinal length-to
      height above the ground ratio (SL:SH) to that of the surrogate. The study
      describes how to build a behavioural classification module and highlights the
      value of using a surrogate for studying cryptic, rare or endangered species. 

PMID- 24031057
TI  - Rolling with the flow: bumblebees flying in unsteady wakes.
AB  - Our understanding of how variable wind in natural environments affects flying
      insects is limited because most studies of insect flight are conducted in either
      smooth flow or still air conditions. Here, we investigate the effects of
      structured, unsteady flow (the von Karman vortex street behind a cylinder) on the
      flight performance of bumblebees (Bombus impatiens). Bumblebees are 'all-weather'
      foragers and thus frequently experience variable aerial conditions, ranging from
      fully mixed, turbulent flow to unsteady, structured vortices near objects such as
      branches and stems. We examined how bumblebee flight performance differs in
      unsteady versus smooth flow, as well as how the orientation of unsteady flow
      structures affects their flight performance, by filming bumblebees flying in a
      wind tunnel under various flow conditions. The three-dimensional flight
      trajectories and orientations of bumblebees were quantified in each of three flow
      conditions: (1) smooth flow, (2) the unsteady wake of a vertical cylinder
      (inducing strong lateral disturbances) and (3) the unsteady wake of a horizontal
      cylinder (inducing strong vertical disturbances). In both unsteady conditions,
      bumblebees attenuated the disturbances induced by the wind quite effectively, but
      still experienced significant translational and rotational fluctuations as
      compared with flight in smooth flow. Bees appeared to be most sensitive to
      disturbance along the lateral axis, displaying large lateral accelerations,
      translations and rolling motions in response to both unsteady flow conditions,
      regardless of orientation. Bees also displayed the greatest agility around the
      roll axis, initiating voluntary casting maneuvers and correcting for lateral
      disturbances mainly through roll in all flow conditions. Both unsteady flow
      conditions reduced the upstream flight speed of bees, suggesting an increased
      cost of flight in unsteady flow, with potential implications for foraging
      patterns and colony energetics in natural, variable wind environments. 

PMID- 24031058
TI  - Lactate kinetics of rainbow trout during graded exercise: do catheters affect the
      cost of transport?
AB  - Changes in lactate kinetics as a function of exercise intensity have never been
      measured in an ectotherm. Continuous infusion of a tracer is necessary to
      quantify rates of lactate appearance (Ra) and disposal (Rd), but it requires
      double catheterization, which could interfere with swimming. Using rainbow trout,
      our goals were to: (1) determine the potential effects of catheters and blood
      sampling on metabolic rate (O2), total cost of transport (TCOT), net cost of
      transport (NCOT) and critical swimming speed (Ucrit), and (2) monitor changes in
      lactate fluxes during prolonged, steady-state swimming or graded swimming from
      rest to Ucrit. This athletic species maintains high baseline lactate fluxes of 24
      MUmol kg(-1) min(-1) that are only increased at intensities >2.4 body lengths
      (BL) s(-1) or 85% Ucrit. As the fish reaches Ucrit, Ra is more strongly
      stimulated (+67% to 40.4 MUmol kg(-1) min(-1)) than Rd (+41% to 34.7 MUmol kg(-1)
      min(-1)), causing a fourfold increase in blood lactate concentration. Without
      this stimulation of Rd during intense swimming, lactate accumulation would
      double. By contrast, steady-state exercise at 1.7 BL s(-1) increases lactate
      fluxes to ~30 MUmol kg(-1) min(-1), with a trivial mismatch between Ra and Rd
      that only affects blood concentration minimally. Results also show that the
      catheterizations and blood sampling needed to measure metabolite kinetics in
      exercising fish have no significant impact on O2 or TCOT. However, these
      experimental procedures affect locomotion energetics by increasing NCOT at high
      speeds and by decreasing Ucrit.

PMID- 24031059
TI  - Phylogenetic analysis of mammalian maximal oxygen consumption during exercise.
AB  - We compiled published values of mammalian maximum oxygen consumption during
      exercise ( ) and supplemented these data with new measurements of for the largest
      rodent (capybara), 20 species of smaller-bodied rodents, two species of weasels
      and one small marsupial. Many of the new data were obtained with running-wheel
      respirometers instead of the treadmill systems used in most previous measurements
      of mammalian . We used both conventional and phylogenetically informed allometric
      regression models to analyze of 77 'species' (including subspecies or separate
      populations within species) in relation to body size, phylogeny, diet and
      measurement method. Both body mass and allometrically mass-corrected showed
      highly significant phylogenetic signals (i.e. related species tended to resemble
      each other). The Akaike information criterion corrected for sample size was used
      to compare 27 candidate models predicting (all of which included body mass). In
      addition to mass, the two best-fitting models (cumulative Akaike weight=0.93)
      included dummy variables coding for three species previously shown to have high
      (pronghorn, horse and a bat), and incorporated a transformation of the
      phylogenetic branch lengths under an Ornstein-Uhlenbeck model of residual
      variation (thus indicating phylogenetic signal in the residuals). We found no
      statistical difference between wheel- and treadmill-elicited values, and diet had
      no predictive ability for . Averaged across all models, the allometric scaling
      exponent was 0.839, with 95% confidence limits of 0.795 and 0.883, which does not
      provide support for a scaling exponent of 0.67, 0.75 or unity. 

PMID- 24031060
TI  - The response of brain serotonergic and dopaminergic systems to an acute stressor
      in rainbow trout: a time course study.
AB  - The brain monoaminergic neurotransmitter systems are known to be involved in the
      integrated response to stress in vertebrates. However, present knowledge about
      the timing of their actions as well as their specific roles in the regulation of
      the endocrine axes that drive the stress response is incomplete. This is partly
      because of the complexity of the reciprocal interactions among the monoaminergic
      systems and other biochemical effectors of the stress response such as
      corticotropin-releasing factor (CRF), arginine vasotocin (AVT),
      adrenocorticotropic hormone (ACTH) and corticosteroids. In this study, we show
      for the first time in teleost fish (rainbow trout) the short- and mid-term time
      course of the response of the forebrain serotonergic and dopaminergic activities
      after exposure to an acute stressor. Other stress markers like the plasma levels
      of cortisol, glucose and lactate were also monitored, providing a context in
      which to precisely locate the monoaminergic activation within the fish acute
      stress response. Our results show that acute stress induced a rapid increase in
      forebrain serotonergic activity, which became elevated after only 15 s of
      chasing. Several hours after stress, serotonergic activity recovered its basal
      levels, in parallel with the recovery of other stress markers such as plasma
      catecholamines and cortisol. Dopaminergic activity was also increased after
      stress, but only in the telencephalon and only after 20 min. The increase in
      serotonergic activity happened before the elevation of plasma catecholamines,
      suggesting that this monoamine system could have a key role in triggering the
      initial steps of the activation of not only the hypothalamus-pituitary-inter
      renal axis but also the brain-sympathetic-chromaffin axis in fish. 

PMID- 24031061
TI  - Complex response in size-related traits of bulb mites (Rhizoglyphus robini) under
      elevated thermal conditions - an experimental evolution approach.
AB  - Temperature is a key environmental factor affecting almost all aspects of life
      history in ectotherms. Theory predicts that they grow faster, reach smaller sizes
      and produce smaller offspring when temperature increases. In addition,
      temperature changes, through their effects on metabolism, may also influence the
      expression of alternative reproductive phenotypes (ARPs) in ectotherms. Although
      many studies have investigated the phenotypic plasticity of life history traits
      in relation to temperature change, little is known about how those traits and
      phenotypic plasticity may evolve together. In our study we subjected bulb mites
      (non-model, soil organisms that normally experience rather stable thermal
      conditions) to experimental evolution in two temperature treatments: control (24
      degrees C) and elevated (28 degrees C). After 18 generations, we measured adult
      body size, egg size and development time of both treatments at control as well as
      at elevated temperatures (test temperatures). Thus, we were able to detect
      genetic changes (the effects of selection temperature) and environmental effects
      (the effects of test temperature). We also observed the ARP expression throughout
      the experimental evolution. Our results revealed quite complex patterns of life
      history in traits response to temperature. Mites developed faster and reached
      smaller sizes at increased temperature, but evolutionary responses to increased
      temperature were not always parallel to the observed phenotypic plasticity.
      Additionally, despite smaller body sizes, females laid larger eggs at higher
      temperature. This effect was more pronounced in animals evolving at elevated
      temperature. Evolution at increased temperature also affected ARP expression,
      with the proportion of armored fighters decreasing from generation to generation.
      We propose that this could be the consequence of temperature sensitivity of the
      cost-to-benefits ratio of expressing ARPs. 

PMID- 24031062
TI  - Drastic reorganization of the bioconvection pattern of Chlamydomonas:
      quantitative analysis of the pattern transition response.
AB  - Motile aquatic microorganisms are known to self-organize into bioconvection
      patterns. The swimming activity of a population of microorganisms leads to the
      emergence of macroscopic patterns of density under the influence of gravity.
      Although long-term development of the bioconvection pattern is important in order
      to elucidate the possible integration of physiological functions of individuals
      through bioconvection pattern formation, little quantitative investigation has
      been carried out. In the present paper, we present the first quantitative
      description of long-term behavior of bioconvection of Chlamydomonas reinhardtii,
      particularly focusing on the 'pattern transition response'. The pattern
      transition response is a sudden breakdown of the steady bioconvection pattern
      followed by re-formation of the pattern with a decreased wavelength. We found
      three phases in the pattern formation of the bioconvection of C. reinhardtii:
      onset, steady-state 1 (before the transition) and steady-state 2 (after the
      transition). In onset, the wavelength of the bioconvection pattern increases with
      increasing depth, but not in steady-states 1 or 2. By means of the newly
      developed two-axis view method, we revealed that the population of C. reinhardtii
      moves toward the bottom of the experimental chamber just before the pattern
      transition. This indicates that the pattern transition response could be caused
      by enhancement of the gyrotaxis of C. reinhardtii as a result of the changes in
      the balance between the gravitactic and gyrotactic torques. We also found that
      the bioconvection pattern changes in response to the intensity of red-light
      illumination, to which C. reinhardtii is phototactically insensitive. These facts
      suggest that the bioconvection pattern has a potential to drastically reorganize
      its convection structure in response to the physiological processes under the
      influence of environmental cues. 

PMID- 24031063
TI  - Coordinated ventilation and spiracle activity produce unidirectional airflow in
      the hissing cockroach, Gromphadorhina portentosa.
AB  - Insects exchange respiratory gases via an extensive network of tracheal vessels
      that open to the surface of the body through spiracular valves. Although gas
      exchange is known to increase with the opening of these spiracles, it is not
      clear how this event relates to gas flow through the tracheal system. We examined
      the relationship between respiratory airflow and spiracle activity in a
      ventilating insect, the hissing cockroach, Gromphadorhina portentosa, to better
      understand the complexity of insect respiratory function. Using simultaneous
      video recordings of multiple spiracular valves, we found that abdominal spiracles
      open and close in unison during periods of ventilation. Additionally, independent
      recordings of CO2 release from the abdominal and thoracic regions and
      observations of hyperoxic tracer gas movement indicate that air is drawn into the
      thoracic spiracles and expelled from the abdominal spiracles. Our video
      recordings suggest that this unidirectional flow is driven by abdominal
      contractions that occur when the abdominal spiracles open. The spiracles then
      close as the abdomen relaxes and fills with air from the thorax. Therefore, the
      respiratory system of the hissing cockroach functions as a unidirectional pump
      through the coordinated action of the spiracles and abdominal musculature. This
      mechanism may be employed by a broad diversity of large insects that respire by
      active ventilation. 

PMID- 24031064
TI  - Mass and volume growth of an insect tracheal system within a single instar.
AB  - Organisms must accommodate oxygen delivery to developing tissues as body mass
      increases during growth. In insects, the growth of the respiratory system has
      been assumed to occur only during molts, whereas body mass and volume increase
      during the larval stages between molts. This decouples whole-body growth from the
      growth of the oxygen supply system. This assumption is derived from the
      observation that the insect respiratory system is an invagination of the
      exoskeleton, which must be shed during molts for continued growth to occur. Here,
      we provide evidence that this assumption is incorrect. We found that the
      respiratory system increases substantially in both mass and volume within the
      last larval instar of Manduca sexta larvae, and that the growth of the
      respiratory system changes with diet quality, potentially as a consequence of
      shifting metabolic demands. 

PMID- 24031065
TI  - Hypoxia delays hematopoiesis: retention of embryonic hemoglobin and erythrocytes
      in larval rainbow trout, Oncorhynchus mykiss, during chronic hypoxia exposure.
AB  - In rainbow trout development, a switch occurs from high-affinity embryonic
      hemoglobin (Hb) and round, embryonic erythrocytes to lower-affinity adult Hb and
      oval, adult erythrocytes. Our study investigated the early ontogeny of rainbow
      trout blood properties and the hypoxia response. We hypothesized that hypoxia
      exposure would delay the ontogenetic turnover of Hb and erythrocytes because
      retention of high-affinity embryonic Hb would facilitate oxygen loading. To test
      this hypothesis we developed a method of efficiently extracting blood from
      individual embryos and larvae and optimized several techniques for measuring
      hematological parameters on microliter (0.5-2.0 MUl) blood samples. In chronic
      hypoxia (30% of oxygen saturation), stage-matched embryos and larvae possessed
      half the Hb concentration, erythrocyte counts and hematocrit observed in
      normoxia. Hypoxia-reared larvae also had threefold to sixfold higher mRNA
      expression of the embryonic Hb alpha-1, beta-1 and beta-2 subunits relative to
      stage-matched normoxia-reared larvae. Furthermore, in hypoxia, the round
      embryonic erythrocytic shape persisted into later developmental stages. Despite
      these differences, Hb-oxygen affinity (P50), cooperativity and the Root effect
      were unaltered in hypoxia-reared O. mykiss. The data support our hypothesis that
      chronic hypoxia delays the ontogenetic turnover of Hb and erythrocytes, but
      without the predicted functional consequences (i.e. higher than expected P50).
      These results also suggest that the Hb-oxygen affinity is protected during
      development in chronic hypoxia to favor oxygen unloading at the tissues. We
      conclude that in early trout development, the blood-oxygen transport system
      responds very differently to chronic hypoxia relative to adults, possibly because
      respiration depends relatively more on oxygen diffusion than convection. 

PMID- 24031066
TI  - Light from down under.
AB  - Coral-algae symbiosis is a key feature of tropical corals and is highly dependent
      on the efficiency with which solar energy is attenuated by the coral.
      Scleractinian corals are among the most efficient light collectors in nature
      because of the modulation of the internal light field in the coral skeleton.
      Interestingly, coral skeleton particles composing the sandy bottoms in reef
      margins sustain these optical characteristics. In the present study, we examined
      two free-living coral species - Heterocyathus aequicostatus (Caryophyllidae) and
      Heteropsammia cochlea (Dendrophylliidae) - common on biogenic coarse carbonate
      sand of the Great Barrier Reef but absent from fine sand at the same depth. In
      coarse carbonate sand, light penetrates a few millimeters below the surface and
      propagates along horizontal distances of a few centimeters. In fine sand, almost
      all of the light is reflected back to the water column. For photosynthetic sand
      dwelling organisms such as the studied species, with over one-third of their
      surface area facing the substrate, light flux to their underside may be
      beneficial. A correlation was found between the diameter of these corals and the
      distance that light may travel in the sand under the coral. Laboratory and field
      measurements show that the symbiotic algae on the underside of the corallites are
      photosynthetically active even when the coral is partially buried, implying
      sufficient light penetration. Other organisms in the study site, such as fungid
      corals and foraminiferans, with different morphologies, have different light
      trapping strategies but are also photosynthesizing on their underside. The
      importance of the substrate type to the performance of the three main partners of
      the symbiosis (coral, endosymbiotic algae and a sipunculan worm) is highlighted,
      and is a striking example of co-evolution. 

PMID- 24031067
TI  - Inflammatory challenge increases measures of oxidative stress in a free-ranging,
      long-lived mammal.
AB  - Oxidative stress - the imbalance between reactive oxygen species (ROS) and
      neutralising antioxidants - has been under debate as the main cause of ageing in
      aerobial organisms. The level of ROS should increase during infection as part of
      the activation of an immune response, leading to oxidative damage to proteins,
      lipids and DNA. Yet, it is unknown how long-lived organisms, especially mammals,
      cope with oxidative stress. Bats are known to carry a variety of zoonotic
      pathogens and at the same time are, despite their high mass-specific basal
      metabolic rate, unusually long lived, which may be partly the result of low
      oxidative damage of organs. Here, we asked whether an immune challenge causes
      oxidative stress in free-ranging bats, measuring two oxidative stress markers. We
      injected 20 short-tailed fruit bats (Carollia perspicillata) with bacterially
      derived lipopolysaccharide (LPS) and 20 individuals with phosphate-buffered
      saline solution (PBS) as a control. Individuals injected with LPS showed an
      immune reaction by increased white blood cell count after 24 h, whereas there was
      no significant change in leukocyte count in control animals. The biological
      antioxidant potential (BAP) remained the same in both groups, but reactive oxygen
      metabolites (ROMs) increased after treatment with LPS, indicating a significant
      increase in oxidative stress in animals when mounting an immune reaction toward
      the inflammatory challenge. Control individuals did not show a change in
      oxidative stress markers. We conclude that in a long-lived mammal, even high
      concentrations of antioxidants do not immediately neutralise free radicals
      produced during a cellular immune response. Thus, fighting an infection may lead
      to oxidative stress in bats. 

PMID- 24031068
TI  - Effects of running on human Achilles tendon length-tension properties in the free
      and gastrocnemius components.
AB  - The elastic properties of the human Achilles tendon are important for locomotion;
      however, in vitro tests suggest that repeated cyclic contractions lead to tendon
      fatigue - an increase in length in response to stress applied. In vivo
      experiments have not, however, demonstrated mechanical fatigue in the Achilles
      tendon, possibly due to the limitations of using two-dimensional ultrasound
      imaging to assess tendon strain. This study used freehand three-dimensional
      ultrasound (3DUS) to determine whether the free Achilles tendon (calcaneus to
      soleus) or the gastrocnemius tendon (calcaneus to gastrocnemius) demonstrated
      tendon fatigue after running exercise. Participants (N=9) underwent 3DUS scans of
      the Achilles tendon during isometric contractions at four ankle torque levels
      (passive, and 14, 42 and 70 N m) before and after a 5 km run at a self-selected
      pace (10-14 km h(-1)). Running had a significant main effect on the length of the
      free Achilles tendon (P<0.01) with a small increase in length across the torque
      range. However, the mean lengthening effect was small (<1%) and was not
      accompanied by a change in free tendon stiffness. There was no significant change
      in the length of the gastrocnemius tendon or the free tendon cross-sectional
      area. While the free tendon was shown to lengthen, the lack of change in
      stiffness suggests the tendon exhibited mechanical creep rather than fatigue.
      These effects were much smaller than those predicted from in vitro experiments,
      possibly due to the different loading profile encountered and the ability of the
      tendon to repair in vivo. 

PMID- 24031069
TI  - Large dermoid cyst of the left hip: radiological approach with histopathology
      assessment.

PMID- 24031070
TI  - Non-syndromic hereditary gingival fibromatosis.
AB  - Hereditary gingival fibromatosis is a rare condition characterised by severe
      gingival hyperplasia that can occur as an isolated disease or as part of a
      syndrome or chromosomal abnormality. In severe cases, the gingival enlargement
      may cover the crowns of teeth and cause severe aesthetic, emotional and
      functional impairment. This case report gives an overview of gingival
      fibromatosis in a 22-year-old male patient who presented with generalised
      gingival enlargement. 

PMID- 24031071
TI  - A benign cancer with malicious paraneoplastic syndromes.
AB  - A 70-year-old retired general practitioner with known follicular lymphoma
      presented with ptosis, dysphagia and progressive weakness in his upper and lower
      limbs. Despite having positive antibodies for myasthenia gravis he did not
      respond to conventional treatment with pyridostigmine, immunoglobulins and
      steroids. After 1 week on a general ward, he required intensive care for non
      invasive ventilation. On the intensive care unit, he developed a secondary
      paraneoplastic syndrome in the form of a syndrome of inappropriate antidiuretic
      hormone secretion and required a tracheostomy for ventilatory support. After 1
      week of invasive ventilation and remaining fully conscious throughout, he
      declined further treatment and passed away. 

PMID- 24031072
TI  - A new syndrome: right-sided arcus aorta syndrome.
AB  - Right-sided arcus aorta (RSAA) is a rare congenital anomaly that may cause
      chronic cough and dyspnoea. We aimed to define RSAA as a new syndrome
      characterised by RSAA, dyspnoea and cough during exercise. RSAA syndrome should
      be included in the differential diagnosis of asthma. 

PMID- 24031073
TI  - Primary penile melanoma with an incidental renal oncocytoma.
AB  - A 57-year-old man presented with a pigmented lesion on the ventral aspect of his
      glans penis. A punch biopsy showed features consistent with malignant melanoma.
      Preoperative staging was initiated with CT of the thorax, abdomen and pelvis. A
      mass in the lower pole of the left kidney was found and given the presence of a
      primary melanoma, was highly suspicious for a metastatic deposit or a primary
      renal cell carcinoma. A biopsy of this mass failed to give a definitive
      diagnosis. The patient proceeded to have a partial penectomy and a left radical
      nephrectomy. The penile lesion was a 2.5 mm malignant melanoma with nodular and
      superficial spreading components. The renal mass turned out to be a benign
      oncocytoma. The final clinical stage of the penile melanoma was pT3a N0 M0. The
      patient received adjuvant interferon therapy. He is well and free of disease
      recurrence at 1-year postsurgery. 

PMID- 24031074
TI  - Profound jaundice in a patient with acute hepatitis C.
AB  - A 52-year-old African-American woman with overall good health and medical history
      of asthma and depression presented with right lower quadrant abdominal pain,
      vomiting and icterus for 3 weeks. Her physical examination was remarkable for
      only sclera icterus and mild tenderness on palpation in the right lower quadrant.
      Investigations revealed marked hyperbilirubinemia and transaminitis, with other
      serological and radiological studies unremarkable and a hepatitis A, B and C
      panel negative 3 weeks before presentation. Repeat hepatitis panel showing
      hepatitis C antibody positive with viral load 20 739 524 IU/mL. Liver biopsy
      supported the diagnosis of acute hepatitis C infection. 

PMID- 24031075
TI  - Hyponatraemia induced hyperCKaemia.
AB  - A 32-year-old woman presented to Kasturba Hospital, Manipal with the features of
      gastroenteritis and one episode of generalised tonic clonic seizure with loss of
      consciousness for 5 min. No abnormalities were found during neurological
      examination. Her baseline investigations showed low sodium, low serum osmolality,
      normal renal and liver function tests, urine myoglobin and antinuclear antibodies
      profile were negative. Incidentally her creatine kinase (CK) levels were found to
      be very high. She was treated with intravenous fluids and high salt diet for
      hyponatraemia. With correction of hyponatraemia, CK levels also improved,
      suggesting the probable diagnosis of hyponatraemia induced myopathy leading to
      hyperCKaemia. The importance of early recognition of this potentially-dangerous
      and rare condition is emphasised. 

PMID- 24031076
TI  - Different diffusion-weighted MRI findings in brainstem neuro-Behcet's disease.

PMID- 24031077
TI  - Virchow's node.

PMID- 24031078
TI  - Patterns of pain medication use during last months of life in HIV-infected
      populations: the experience of an academic outpatient clinic.
AB  - INTRODUCTION: This article describes the patterns of use of pain medicines of HIV
      infected patients during last months of life in an HIV university-affiliated
      outpatient clinic. METHODS: We retrospectively reviewed our databases and
      identified patients who died over the last 12 months in our clinic. Demographic,
      clinical, and laboratory information were abstracted. RESULTS: A total of 41
      patients died in our HIV outpatient clinic in a period of 12 months. Opioid
      analgesics were prescribed for 21 (51%) patients, with 10 (48%) of these patients
      prescribed short-acting opioid analgesics alone, In all, 11 patients (52%) were
      on a short-acting and long-acting opioid combination, and 30 (73%) patients
      experienced pain that was not adequately controlled. DISCUSSION: Pain control
      during the last months of life for this population appears to be suboptimal.
      Better strategies are needed.

PMID- 24031079
TI  - The family conference in palliative medicine: a practical approach.
AB  - A family conference (FC) is an opportunity for the family and their physician to
      share their knowledge and concerns about the physical and psychosocial dimensions
      of care. Appropriate communication principles and practice are both important for
      an effective FC. The FCs guided by common sense principles and sound clinical
      practice (good structure, content, and process) have beneficial outcomes. (1)
      Creation of a therapeutic partnership so the family and medical team collaborate
      in the difficult task of sophisticated medical and psychosocial care of a complex
      illness. (2) Enhanced therapeutic management through education and support of the
      patient and primary caregiver (and other family members) to facilitate self
      efficacy and convey realistic hope with careful sequencing of key messages. (3)
      Easier patient transitions from cure- to care-oriented management, with a formal
      (yet thoughtful and gentle) introduction to the principles and practice of modern
      palliative medicine.

PMID- 24031080
TI  - Comparison of accuracy among prognostic scores for predicting life expectancy in
      Korean patients with cancer with weeks of survival.
AB  - To compare the accuracy among 4 prognostic scores (Palliative Prognostic Score
      (PaP), Delirium-PaP (D-PaP), Palliative Prognostic Index (PPI), Objective
      Prognostic Score (OPS)) for predicting life expectancy in Korean cancer patients
      with weeks of survival, we conducted a retrospective study by reviewing medical
      records of 94 patients and compared the accuracy of 3-week and 30-day survival
      among the 4 prognostic scores. Three-week survival estimates were highest for the
      PaP and 30-day estimates were similar for the 4 prognostic scores. Area under the
      receiver operating characteristic curve was highest for the PaP and lowest for
      the PPI, but there were no significant differences. The prognostics scores did
      not differ from each other in a significant manner. 

PMID- 24031081
TI  - Use of data envelopment analysis to quantify opportunities for antibacterial
      targets for reduction of health care-associated Clostridium difficile infection.
AB  - Clostridium difficile infection (CDI) is an important health care-associated
      infection that leads to increased morbidity and mortality. Antibacterial
      medications used in hospitals serve as targets for antibacterial stewardship
      programs to reduce C difficile. The objective was to create a benchmark strategy
      targeting high-risk antibacterials for C difficile. This was a retrospective
      cross-sectional study using claims data from 58 hospitals. The Data Envelopment
      Analysis Technique was used to identify best-practice hospitals in terms of less
      use of 5 classes of antibacterials and fewer CDIs. Of 58 hospitals, 17 (29%) were
      identified as best-practice hospitals. Antibacterial classes requiring the
      greatest percentage reduction in use in non-best-practice hospitals versus best
      practice hospitals were clindamycin (31%), beta-lactam/beta-lactamase
      combinations (30%), and carbapenems (29%). This study suggests that there are
      areas of improvement in high-risk antibacterial use that could lead to decreased
      CDIs. 

PMID- 24031082
TI  - The effectiveness of chemoradiation therapy and salvage surgery for
      hypopharyngeal squamous cell carcinoma.
AB  - OBJECTIVE: The objective of this study was to evaluate the results of salvage
      surgery after definitive chemoradiation for hypopharyngeal squamous cell
      carcinoma. METHODS: This was a retrospective cohort study. Of the 79 patients
      with previously untreated hypopharyngeal squamous cell carcinoma who received
      definitive chemoradiation from January 2004 to January 2009, 24 who had
      recurrence and underwent salvage surgery at the National Cancer Center Hospital
      East, Chiba, Japan, were enrolled in this study. RESULTS: Of the 24 patients who
      underwent salvage surgery with curative intent, 13 had an isolated local failure,
      eight had an isolated neck failure and three had combined local and regional
      failure. Postoperative surgical complications were observed in eight (33.3%)
      patients. Of the 24 patients undergoing salvage surgery, 12 (50%) had recurrence.
      In 11 of these patients, death ensued from salvage failure, defined as the
      presence of any recurrence after salvage treatment. The causes of cancer-specific
      death ensuing from salvage failure were regional recurrence of the tumor (n = 6)
      (one of whom had concurrent distant metastases) and distant metastases alone (n =
      5). No local recurrence after salvage surgery was observed in our group of
      patients. The disease-free and overall 24-month survival rates were 49.0 and
      50.0%, respectively. Those patients who initially presented with unresectable
      disease had lower overall survival compared with those who initially presented
      with resectable disease (P = 0.0003). CONCLUSIONS: The oncologic outcomes were
      acceptable in those patients in whom salvage surgery was carried out. Those who
      initially presented with unresectable disease had a poor prognosis.

PMID- 24031083
TI  - Grb14 as an independent good prognosis factor for breast cancer patients treated
      with neoadjuvant chemotherapy.
AB  - OBJECTIVE: Growth factor receptor-binding protein 14, a new member of
      noncatalytic adaptor proteins family, has been shown to be upregulated in breast
      cancer. We investigated the prognostic value of growth factor receptor-binding
      protein 14 expression in breast cancer patients treated with neoadjuvant
      chemotherapy. METHODS: Primary breast cancer specimens were taken from locally
      advanced breast cancer patients in a Phase II clinical trial of neoadjuvant
      chemotherapy and the expression pattern of growth factor receptor-binding protein
      14 was determined by immunohistochemistry. Kaplan-Meier analysis and Cox
      regression model were used to assess disease-free and overall survival, according
      to the expression of growth factor receptor-binding protein 14 in tumor cells.
      RESULTS: Our result showed that growth factor receptor-binding protein 14 was
      highly expressed in 23.1% of breast cancer sections, and high expression of
      growth factor receptor-binding protein 14 was significantly associated with
      better disease-free (P = 0.016, hazard ratio 0.07, 95% confidence interval 0.06
      0.08) and overall survival (P = 0.004, hazard ratio 0.02, 95% confidence interval
      0.02-0.03), compared with the low-expression group. Multivariate analysis
      indicated that high expression of growth factor receptor-binding protein 14 was
      an independent good prognostic factor for both disease-free (P = 0.04, hazard
      ratio 0.37, 95% confidence interval 0.14-0.98) and overall survival (P = 0.03,
      hazard ratio 0.11, 95% confidence interval 0.10-0.82). CONCLUSIONS: High
      expression of growth factor receptor-binding protein 14 in breast cancer cells
      may help to identify low-risk patients for additional therapies after neoadjuvant
      chemotherapy.

PMID- 24031084
TI  - Outcome analysis of salvage radiotherapy for occult cervical cancer found after
      simple hysterectomy.
AB  - OBJECTIVE: The objective was to analyze the outcomes of the patients, who
      received salvage radiotherapy for incidentally discovered cervical cancer
      following simple hysterectomy, and to identify the influence of intracavitary
      radiotherapy on treatment outcomes. METHODS: Data from 117 patients with occult
      cervical cancer who underwent simple hysterectomy followed by salvage
      radiotherapy from September 1979 to November 2010 were collected. All the
      patients received external beam radiotherapy with (n = 45) or without (n = 72)
      intracavitary radiotherapy. Local control, disease-free survival, overall
      survival and treatment-related toxicity were investigated. RESULTS: The median
      follow-up time was 75 months. The 5- and 10-year local control/disease-free
      survival/overall survival rates were 93/87/87% and 90/84/83%, respectively. Among
      98 patients who had no residual disease and negative resection margin on surgical
      specimens, 32 (33%) received intracavitary radiotherapy and 66 (67%) did not.
      There were no differences in patient and tumor characteristics between patients
      treated with and without intracavitary radiotherapy. The 5-year local control
      rate for the non-intracavitary radiotherapy group was 93 versus 94% for the
      intracavitary radiotherapy group (P = 0.564); the disease-free survival rate was
      88 versus 94% (P = 0.894); the overall survival rate was 95 versus 85% (P =
      0.106), respectively. Among all patients, there were 5% of Grade 3 or higher late
      toxicities. CONCLUSIONS: Patients with occult invasive cervical cancer discovered
      following simple hysterectomy could be treated safely and effectively with
      salvage radiotherapy. For patients with no residual disease and negative
      resection margin, intracavitary radiotherapy could be omitted.

PMID- 24031085
TI  - Assessment and management of renal impairment in chemotherapy for urogenital
      cancer.
AB  - The method of diagnosing chronic kidney disease by simple estimated glomerular
      filtration rate equations has demonstrated a high prevalence of chronic kidney
      disease among the genitourinary cancer patients. Approximately 30-50% of
      urothelial cancer patients have Grade 3 chronic kidney disease before
      chemotherapy, and the rate increases to around 80% in upper urinary tract cancer
      patients who have undergone radical surgery. Several gold-standard treatments,
      including cisplatin for urothelial/testicular tumors and anti-vascular
      endothelial growth factor therapy for kidney cancers, are known to be associated
      with the development of renal impairment. However, which renal function
      assessments are best to select a chemotherapy regimen remain unknown. Most
      testicular tumor patients are cured by intensive combined chemotherapy with
      cisplatin, but chemotherapy can induce chronic kidney disease in testicular
      cancer survivors. The prevalence of Stage 3 chronic kidney disease among the
      testicular cancer survivors is between 10 and 20%. Thus, the estimated glomerular
      filtration rate assessment is a useful tool for monitoring the development of
      chronic kidney disease among the cancer survivors, and assessment of renal
      function is mandatory before the treatment of these genitourinary cancer
      patients. 

PMID- 24031086
TI  - Psychotropic medication use among children with autism spectrum disorders within
      the Simons Simplex Collection: are core features of autism spectrum disorder
      related?
AB  - Psychotropic medication use and its relationship to autism spectrum core features
      were examined in a well-characterized but nonstratified North American sample (N
      = 1605) of children/adolescents diagnosed with autism spectrum disorders
      utilizing the Autism Diagnostic Observation Schedule and the Autism Diagnostic
      Interview-Revised, from the multisite Simons Simplex Collection. Analyses
      included (a) prevalence of psychotropic use (overall, and by classes), (b)
      correlations between prevalence of use and autism spectrum core features, age,
      and cognitive functioning, and (c) logistic regression to identify whether these
      factors were predictive of psychotropic use. Results indicated 41.7% ever used
      one or more classes of psychotropic medications, with attention deficit
      hyperactivity disorder medications used most. Small but significant correlations
      between psychotropic medication use and (a) social impairment (p < .001) and (b)
      repetitive behaviors (p < .001) were found. Overall, however, autism spectrum
      disorder core features are weakly related to medication use. Older children used
      more psychotropics (p < .001), and higher cognitive functioning was associated
      with less overall psychotropic use (p < .001). Logistic regression indicated that
      use of psychotropics was predicted by repetitive behaviors (both clinician
      observed and parent-reported), age, and cognitive ability level. Limitations
      inherent to the Simons Simplex Collection sample, methodology, and the
      correlational analyses are discussed. Directions for future research include
      investigation of factors more influential than core symptoms on psychotropic
      treatment (e.g. parent perceptions, comorbid symptoms). 

PMID- 24031087
TI  - Insight into the mechanisms of action of estrogen receptor beta in the breast,
      prostate, colon, and CNS.
AB  - Estrogen and its receptors (ERs) influence many biological processes in
      physiology and pathology in men and women. ERs are involved in the etiology
      and/or progression of cancers of the prostate, breast, uterus, ovary, colon,
      lung, stomach, and malignancies of the immune system. In estrogen-sensitive
      malignancies, ERbeta usually is a tumor suppressor and ERalpha is an oncogene.
      ERbeta regulates genes in several key pathways including tumor suppression (p53,
      PTEN); metabolism (PI3K); survival (Akt); proliferation pathways (p45(Skp2),
      cMyc, and cyclin E); cell-cycle arresting factors (p21(WAF1), cyclin-dependent
      kinase inhibitor 1 (CDKN1A)), p27(Kip1), and cyclin-dependent kinases (CDKs);
      protection from reactive oxygen species, glutathione peroxidase. Because they are
      activated by small molecules, ERs are excellent targets for pharmaceuticals.
      ERalpha antagonists have been used for many years in the treatment of breast
      cancer and more recently pharmaceutical companies have produced agonists which
      are very selective for ERalpha or ERbeta. ERbeta agonists are being considered
      for preventing progression of cancer, treatment of anxiety and depression, as
      anti-inflammatory agents and as agents, which prevent or reduce the severity of
      neurodegenerative diseases. 

PMID- 24031088
TI  - 3,5-di-iodothyronine stimulates tilapia growth through an alternate isoform of
      thyroid hormone receptor beta1.
AB  - Recent studies in our laboratory have shown that in some teleosts, 3,5-di
      iodothyronine (T2 or 3,5-T2) is as bioactive as 3,5,3'-tri-iodothyronine (T3) and
      that its effects are in part mediated by a TRbeta1 (THRB) isoform that contains a
      9-amino acid insert in its ligand-binding domain (long TRbeta1 (L-TRbeta1)),
      whereas T3 binds preferentially to a short TRbeta1 (S-TRbeta1) isoform that lacks
      this insert. To further understand the functional relevance of T2 bioactivity and
      its mechanism of action, we used in vivo and ex vivo (organotypic liver cultures)
      approaches and analyzed whether T3 and T2 differentially regulate the S-TRbeta1
      and L-TRbeta1s during a physiological demand such as growth. In vivo, T3 and T2
      treatment induced body weight gain in tilapia. The expression of L-TRbeta1 and S
      TRbeta1 was specifically regulated by T2 and T3 respectively both in vivo and ex
      vivo. The TR antagonist 1-850 effectively blocked thyroid hormone-dependent gene
      expression; however, T3 or T2 reversed 1-850 effects only on S-TRbeta1 or L
      TRbeta1 expression, respectively. Together, our results support the notion that
      both T3 and T2 participate in the growth process; however, their effects are
      mediated by different, specific TRbeta1 isoforms. 

PMID- 24031089
TI  - Mutations in SLC35A3 cause autism spectrum disorder, epilepsy and arthrogryposis.
AB  - BACKGROUND: The heritability of autism spectrum disorder is currently estimated
      at 55%. Identification of the molecular basis of patients with syndromic autism
      extends our understanding of the pathogenesis of autism in general. The objective
      of this study was to find the gene mutated in eight patients from a large
      kindred, who suffered from autism spectrum disorder, arthrogryposis and epilepsy.
      METHODS AND RESULTS: By linkage analysis and exome sequencing, we identified
      deleterious mutations in SLC35A3 in these patients. SLC35A3 encodes the major
      Golgi uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) transporter. In Golgi
      vesicles isolated from patient fibroblasts the transport of the respective
      nucleotide sugar was significantly reduced causing a massive decrease in the
      content of cell surface expressed highly branched N-glycans and a concomitant
      sharp increase of lower branched glycoforms. CONCLUSIONS: Spontaneous mutation in
      SLC35A3 has been discovered in cattle worldwide, recapitulating the human
      phenotype with arthrogryposis and additional skeletal defects known as Complex
      Vertebral Malformation syndrome. The skeletal anomalies in the mutant cattle and
      in our patients, and perhaps even the neurological symptoms are likely the
      consequence of the lack of high-branched N-glycans and the concomitant abundance
      of lower-branched glycoforms at the cell surface. This pattern has previously
      been associated with growth arrest and induction of differentiation. With this
      study, we add SLC35A3 to the gene list of autism spectrum disorders, and
      underscore the crucial importance of UDP-GlcNAc in the regulation of the N-glycan
      branching pathway in the Golgi apparatus.

PMID- 24031091
TI  - Greater prevalence of PROKR2 mutations in Kallmann syndrome patients from the
      Maghreb than in European patients.
AB  - CONTEXT: Kallmann syndrome (KS) is a genetically heterogeneous developmental
      disorder that associates hypogonadotropic hypogonadism and anosmia. Various
      causative genes have been identified, but their respective involvement in
      different world regions is poorly documented. OBJECTIVE: We aimed to compare the
      prevalence of mutations in five routinely analyzed KS genes between Maghrebian
      and European patients. METHODS: Blood samples from 120 presumably unrelated
      Maghrebian patients were collected for DNA sequencing by the Sanger technique.
      The prevalence of the non-synonymous mutations in KAL1, FGFR1, FGF8, PROKR2, and
      PROK2 was determined for each gene, and compared with those previously obtained
      from the analysis of 712 European patients. RESULTS: Diverse mutations in PROKR2,
      a gene involved both in monogenic recessive and digenic/oligogenic KS
      transmission modes, were found in 23.3% of the Maghrebian patients, but only in
      5.1% of the European patients (Fisher's exact test, P<0.001), whereas mutations
      in each of the other four KS genes were present either at similar frequencies in
      the Maghrebian and European patients (KAL1, PROK2, FGF8, from 6.6 to 0.8%;
      Fisher's exact test, P>0.4 for all comparisons) or at a lower frequency in
      Maghrebian patients (FGFR1, 5.0 vs 11.7%; Fisher's exact test, P<0.05).
      Homozygosity resulting from consanguineous marriages was not sufficient to
      account for the greater prevalence of PROKR2 mutations in the Maghrebian
      patients. CONCLUSIONS: The great prevalence of PROKR2 mutations in Maghrebian
      patients has practical consequences for molecular diagnosis of the disease and
      genetic counseling in the Maghrebian population.

PMID- 24031090
TI  - Therapy of endocrine disease: Perspectives on the management of adrenal
      insufficiency: clinical insights from across Europe.
AB  - BACKGROUND: Conventional glucocorticoid (GC) replacement for patients with
      adrenal insufficiency (AI) is inadequate. Patients with AI continue to have
      increased mortality and morbidity and compromised quality of life despite
      treatment and monitoring. OBJECTIVES: i) To review current management of AI and
      the unmet medical need based on literature and treatment experience and ii) to
      offer practical advice for managing AI in specific clinical situations. METHODS:
      The review considers the most urgent questions endocrinologists face in managing
      AI and presents generalised patient cases with suggested strategies for
      treatment. RESULTS: Optimisation and individualisation of GC replacement remain a
      challenge because available therapies do not mimic physiological cortisol
      patterns. While increased mortality and morbidity appear related to inadequate GC
      replacement, there are no objective measures to guide dose selection and
      optimisation. Physicians must rely on experience to recognise the clinical signs,
      which are not unique to AI, of inadequate treatment. The increased demand for
      corticosteroids during periods of stress can result in a life-threatening adrenal
      crisis (AC) in a patient with AI. Education is paramount for patients and their
      caregivers to anticipate, recognise and provide proper early treatment to prevent
      or reduce the occurrence of ACs. CONCLUSIONS: This review highlights and offers
      suggestions to address the challenges endocrinologists encounter in treating
      patients with AI. New preparations are being developed to better mimic normal
      physiological cortisol levels with convenient, once-daily dosing which may
      improve treatment outcomes.

PMID- 24031092
TI  - Smaller grey matter volumes in the anterior cingulate cortex and greater
      cerebellar volumes in patients with long-term remission of Cushing's disease: a
      case-control study.
AB  - OBJECTIVE: Patients with long-term remission of Cushing's disease (CD) have
      persistent psychological and cognitive impairments. It is unknown whether, and to
      what extent, these impairments are accompanied by structural abnormalities in the
      brain. We aim to investigate structural changes in the brain in patients with
      predominantly long-term remission of CD and to examine whether these changes are
      associated with psychological and cognitive dysfunction and clinical severity.
      DESIGN: A cross-sectional, case-control study. METHODS: In 25 patients with
      predominantly long-term remission of CD and 25 matched healthy controls, grey
      matter volumes in the regions of interest (hippocampus, amygdala, and anterior
      cingulate cortex (ACC)) and in the whole brain were examined, using 3T magnetic
      resonance imaging and a voxel-based morphometry approach. Psychological and
      cognitive functioning were assessed using validated questionnaires and clinical
      severity was assessed using the Cushing's syndrome severity index. RESULTS:
      Compared with controls, patients had smaller grey matter volumes of areas in the
      ACC (on average 14%, P<0.05) and greater volume of the left posterior lobe of the
      cerebellum (on average 34%, P<0.05). As expected, patients with remitted CD
      reported more depressive symptoms (P=0.005), more anxiety (P=0.003), more social
      phobia (P=0.034), more apathy (P=0.002), and more cognitive failure (P=0.023)
      compared with controls, but the differences in grey matter volumes were not
      associated with psychological or cognitive measures, nor with clinical severity.
      CONCLUSION: Patients with predominantly long-term remission of CD showed specific
      structural brain abnormalities, in the presence of psychological dysfunction. Our
      data form a basis for future work aimed at elucidating the relation of the
      structural brain abnormalities and the sustained psychological deficits after
      long-term exposure to high cortisol levels.

PMID- 24031093
TI  - Does thyroid function influence fracture risk? Prospective data from the HUNT2
      study, Norway.
AB  - OBJECTIVE: To prospectively study the relation between TSH and risk of hip and
      forearm fractures. DESIGN: A population-based cohort study. METHODS: In a
      substudy of the second survey of the Nord Trondelag Health Study, Norway (HUNT2,
      1995-97), linked with a hospital-based fracture registry, we investigated the
      relation between baseline TSH and risk of hip and/or forearm fractures.
      POPULATION: A total of 16 610 women and 8595 men aged 40 years or more, without
      previous self-reported thyroid disease and hip or forearm fractures. RESULTS:
      During 12.5 years follow-up, a total of 1870 women and 342 men experienced hip or
      forearm fractures. Overall, there was no relation between baseline TSH and
      fracture risk. However, there was weak evidence that women with TSH <0.5 and >3.5
      mU/l had a slightly increased risk of hip fractures (hazard ratio (HR) 1.30, 95%
      CI 0.97-1.94 and HR 1.19, 95% CI 0.93-1.52) compared with the reference group
      with TSH of 1.5-2.4 mU/l. Supplementary analyses showed higher hip fracture risk
      in women with TSH >4.0 mU/l and negative thyroid peroxidase antibodies (TPOAb)
      compared with the reference group (HR 1.75, 95% CI 1.24-2.46). CONCLUSION: We
      found no statistically significant relation between baseline TSH and subsequent
      fracture risk, but the data suggest a weak positive association with hip fracture
      risk among women with both low and high TSH. The latter association was confined
      to women with negative TPOAb status.

PMID- 24031094
TI  - Harvester ants use interactions to regulate forager activation and availability.
AB  - Social groups balance flexibility and robustness in their collective response to
      environmental changes using feedback between behavioural processes that operate
      at different timescales. Here we examine how behavioural processes operating at
      two timescales regulate the foraging activity of colonies of the harvester ant,
      Pogonomyrmex barbatus, allowing them to balance their response to food
      availability and predation. Previous work showed that the rate at which foragers
      return to the nest with food influences the rate at which foragers leave the
      nest. To investigate how interactions inside the nest link the rates of returning
      and outgoing foragers, we observed outgoing foragers inside the nest in field
      colonies using a novel observation method. We found that the interaction rate
      experienced by outgoing foragers inside the nest corresponded to forager return
      rate, and that the interactions of outgoing foragers were spatially clustered.
      Activation of a forager occurred on the timescale of seconds: a forager left the
      nest 3-8 s after a substantial increase in interactions with returning foragers.
      The availability of outgoing foragers to become activated was adjusted on the
      timescale of minutes: when forager return was interrupted for more than 4-5 min,
      available foragers waiting near the nest entrance went deeper into the nest.
      Thus, forager activation and forager availability both increased with the rate at
      which foragers returned to the nest. This process was checked by negative
      feedback between forager activation and forager availability. Regulation of
      foraging activation on the timescale of seconds provides flexibility in response
      to fluctuations in food abundance, whereas regulation of forager availability on
      the timescale of minutes provides robustness in response to sustained disturbance
      such as predation.

PMID- 24031095
TI  - A Porous Media Model for Blood Flow within Reticulated Foam.
AB  - A porous media model is developed for non-Newtonian blood flow through
      reticulated foam at Reynolds numbers ranging from 10-8 to 10. This empirical
      model effectively divides the pressure gradient versus flow speed curve into
      three regimes, in which either the non-Newtonian viscous forces, the Newtonian
      viscous forces, or the inertial fluid forces are most prevalent. When compared to
      simulation data of blood flow through two reticulated foam geometries, the model
      adequately captures the pressure gradient within all three regimes, especially
      that within the Newtonian regime where blood transitions from a power-law to a
      constant viscosity fluid.

PMID- 24031096
TI  - Gold Nanoparticle Based Surface Enhanced Fluorescence For Detection of
      Organophosphorus Agents.
AB  - Organophosphorus agents (OPA) represent a serious concern to public safety as
      nerve agents and pesticides. Here we report the development of gold nanoparticle
      based surface enhanced fluorescence (NSEF) spectroscopy for rapid and sensitive
      screening of organophosphorus agents. Fluorescent from Eu3+ ions that are bound
      within the electromagnetic field of gold nanoparticles exhibit a strong
      enhancement. In the presence of OPA, Eu3+ ions are released from the gold
      nanoparticle surface and thus a very distinct fluorescence signal change was
      observed. We discussed the mechanism of fluorescence enhancement and the role of
      OPA for fluorescence intensity change in the presence of gold nanoparticles.

PMID- 24031097
TI  - Complex Families and Late-Life Outcomes Among Elderly Persons: Disability,
      Institutionalization, and Longevity.
AB  - The authors examined the effects of marital status and family structure on
      disability, institutionalization, and longevity for a nationally representative
      sample of elderly persons using Gompertz duration models applied to longitudinal
      data from 3 cohorts of the Health and Retirement Study (N = 11,481). They found
      that parents with only stepchildren have worse outcomes than parents with only
      biological children. Elderly mothers with only stepchildren become disabled and
      institutionalized sooner, and elderly men with only stepchildren have shorter
      longevity relative to their counterparts with only biological children. The
      effect of membership in a blended family differs by gender. Relative to those
      with only biological children, women in blended families have greater longevity
      and become disabled later, whereas men in blended families have reduced
      longevity. The findings indicate that changing marital patterns and increased
      complexity in family life have adverse effects on late-life health outcomes.

PMID- 24031098
TI  - AERODYNAMIC SOUND OF A BODY IN ARBITRARY, DEFORMABLE MOTION, WITH APPLICATION TO
      PHONATION.
AB  - The method of tailored Green's functions advocated by Doak (Proceedings of the
      Royal Society A254 (1960) 129 - 145.) for the solution of aeroacoustic problems
      is used to analyse the contribution of the mucosal wave to self-sustained
      modulation of air flow through the glottis during the production of voiced
      speech. The amplitude and phase of the aerodynamic surface force that maintains
      vocal fold vibration are governed by flow separation from the region of minimum
      cross-sectional area of the glottis, which moves back and forth along its
      effective length accompanying the mucosal wave peak. The correct phasing is
      achieved by asymmetric motion of this peak during the opening and closing phases
      of the glottis. Limit cycle calculations using experimental data of Berry et al.
      (Journal of the Acoustical Society of America 110 (2001) 2539 - 2547.) obtained
      using an excised canine hemilarynx indicate that the mechanism is robust enough
      to sustain oscillations over a wide range of voicing conditions.

PMID- 24031100
TI  - Changing Intergroup Boundaries in Brazilian Marriages: 1991-2008.

PMID- 24031099
TI  - The regio- and stereochemical course of reductive cross-coupling reactions
      between 1,3-disubstituted allenes and vinylsilanes: Synthesis of (Z)-dienes.
AB  - In investigations aimed at exploring the potential of disubstituted allenes in
      stereoselective synthesis, we report studies that explore the reductive cross
      coupling reaction of vinylsilanes with a range of substituted allenes.
      Regiochemical control is attained by employing allenic alkoxides, where the
      proximal heteroatom dictates the site-selectivity in a process that proceeds by
      net formal metallo-[3,3] rearrangement (directed carbometalation/elimination).
      Stereoselectivity in these reactions is complex, with both the nature of allene
      substitution and relative stereochemistry of the substrate impacting the
      stereoselective generation of each alkene of a substituted 1,3-diene. 2009
      Elsevier Ltd. All rights reserved.

PMID- 24031101
TI  - De novo malignant optic chiasm glioma with initial clinical response to steroids.
AB  - Malignant optic nerve glioma (MONG) is a rare but uniformly fatal disease that
      remains poorly understood. We describe a notable case of this rare disease
      occurring in the optic chiasm. Normal brain imaging and normal ophthalmic
      examination two years prior to diagnosis provide evidence for de novo genesis of
      MONG in our patient. Early response to steroids highlights the degree to which
      MONG can initially mimic inflammatory optic neuropathies and chiasmal syndromes.
      Our case also demonstrates a poor outcome with MONG even with current advanced
      therapy for glioblastoma including radiotherapy plus concomitant and adjuvant
      temozolomide (the EORTC/NCIC regimen) and bevacizumab.

PMID- 24031102
TI  - Adaptive midlife defense mechanisms and late-life health.
AB  - A growing body of research suggests that personality characteristics relate to
      physical health; however, this relation ship has primarily been tested in cross
      sectional studies that have not followed the participants into old age. The
      present study utilizes data from a 70-year longitudinal study to prospectively
      examine the relationship between the adaptive defense mechanisms in midlife and
      objectively assessed physical health in late life. In addition to examining the
      direct effect, we test whether social support mediates this relation ship. The
      sample consisted of 90 men who were followed for over seven decades beginning in
      late adolescence. Health ratings from medical records were made at three time
      points (ages 70, 75, and 80). Defense mechanisms were coded from narratives by
      trained independent raters (Vaillant, Bond, & Vaillant, 1986). Independent raters
      assessed social supports between ages 50 and 70. More adaptive defenses in
      midlife were associated with better physical health at all three time points in
      late life. These relationships were partially mediated by social support.
      Findings are consistent with the theory that defense maturity is important for
      building social relationships, which in turn contribute to better late-life
      physical health. Psychological interventions aimed at improving these domains may
      be beneficial for physical health.

PMID- 24031103
TI  - Epidemiology of inflammatory bowel diseases in iran and Asia; a mini review.
AB  - The prevalence of inflammatory bowel diseases (IBDs) is set to stabilize in
      Western Europe and North America, as opposed to its increasing trend in
      developing countries in Asia. The epidemiology of IBDs in areas where the
      incidence and prevalence are relatively low provides an opportunity for
      researchers to determine the unknown aspects of them. In this review article, the
      PubMed and MEDLINE databases were searched from 1970 to 2012 and the
      epidemiological aspects assessed in Iranian articles were compared with identical
      subjects in other Asian countries. During this period, there were 21 documented
      articles on IBD epidemiology in Iran and 52 in Asia. According to the present
      review, CTLA-gene polymorphism and male/female ratio in ulcerative colitis (UC),
      incidence of extra-intestinal manifestations, extent of intestinal involvement,
      and family history in both UC and Crohn's disease (CD) seemed to be different
      between Asia and Iran. In contrast, the incidence of primary sclerosing
      cholangitis in IBD patients and association between NO2/CARD15 mutation and CD as
      C3435-T allele and UC were nearly the same. The rate of IBD has increased
      significantly in Iran, as has that of other Asian countries during the last
      decade. A thorough, well-designed, population-based, multi-regional epidemiologic
      study seems mandatory due to the substantial demographic and characteristic
      variability in IBD patients in our region. 

PMID- 24031104
TI  - Randomized clinical trial of intravenous valproate (orifil) and dexamethasone in
      patients with migraine disorder.
AB  - BACKGROUND: Intravenous Valproate (IVVP) has been used in the treatment of
      migraine in some studies; however, it is far better known in the management of
      status epilepticus. METHODS: Consecutive patients with migraine in our Headache
      Clinic were enrolled in this prospective, randomized clinical trial in 2011. The
      patients were randomized into two therapeutic groups, one receiving 900 mg IVVP
      (Orifil) and the other 16 mg IV Dexamethasone (IVDEX) diluted in 150 CC normal
      saline and infused for 10 minutes. Worst severity of pain before treatment and
      least severity at 3 hours after the infusion using a 0-10 point numeric rating
      scale were recorded. An interview with the patient was performed 72 hours after
      treatment to detect a possible relapse of headache. RESULTS: Thirty-one migraine
      status patients, comprising 28 women and 3 men at a mean+/-SD age of 33.355+/
      12.373 SD, were investigated. Differences in the therapeutic effects of IVVP
      (Orifil) and IVDEX on pain score were not significant between the two groups
      (t=0.933, df=29; P=0.358). Relapse of headache occurred in 68.42% of the IVVP
      (Orifil) group and 66.67% of the IVDEX group. Distribution of relapse was not
      significantly different between the two therapeutic groups of patients (P=0.870).
      CONCLUSION: IVVP (Orifil) was similar in efficacy to IVDEX as abortive therapy in
      patients with migraine status. IVVP (Orifil) appears to offer a safe and well
      tolerated abortive treatment. TRIAL REGISTRATION NUMBER: IRCT13891146234N2.

PMID- 24031105
TI  - Nested polymerase chain reaction and sequence- based detection of leishmania
      infection of sand flies in recently emerged endemic focus of zoonotic cutaneous
      leishmaniasis, southern iran.
AB  - BACKGROUND: Geographical distribution of zoonotic cutaneous leishmaniasis (ZCL)
      has continuously been extended in recent years in Iran. The Beiza District is one
      of the newly-emerged endemic foci of ZCL in southern Iran. The main aim of the
      present study was to detect the vector(s) of ZCL in this area. METHODS: To detect
      the fauna and vectors of ZCL in this district, sand flies were caught using
      sticky papers. Seventy randomly selected female sand flies out of 730 were
      molecularly investigated for Leishmania infection using species-specific nested
      polymerase chain reaction (PCR) assay between April and October 2010. RESULTS: A
      total of 2543 sand flies were caught. The fauna was identified as 10 species
      (five Phlebotomus spp. and five Sergentomyia spp.). Phlebotomus papatasi was the
      most dominant species both indoors and outdoors (37.55% and 16.35 %,
      respectively). L. major was detected in 5 out of 48 investigated Phlebotomus
      papatasi (10.41%). Sequence-based characterization was carried out to confirm the
      PCR findings. The positive samples were shown to have 75-88% similarity with L.
      major sequences in GenBank. CONCLUSION: According to the findings of the present
      study, similar to the other foci of ZCL in Iran, P. papatasi is the proven and
      primary vector of CL. This study could be drawn upon for future strategy planning
      in this newly emerged endemic focus.

PMID- 24031106
TI  - Effects of pentoxifylline on oxygenation and exercise tolerance in patients with
      severe chronic obstructive pulmonary disease.
AB  - BACKGROUND: It was hypothesized that the use of Pentoxifylline would increase
      arterial O2 saturation and increase exercise tolerance in patients with Chronic
      Obstructive Pulmonary Disease (COPD). METHODS: We tested this hypothesis in 23
      patients with COPD and pulmonary hypertension. Patients were randomized to
      receive Pentoxifylline or placebo, each for a 12-week period, in a prospective,
      double-blind study to assess the effects of Pentoxifylline on oxygen saturation
      and exercise tolerance via pulse oximetry and the 6-Minute Walk Test (6MWT).
      RESULTS: At the end of the 12 weeks, the six-minute walk distance rose from
      351.9+/-65 meters to 393+/-67 meters in the Pentoxifylline group (10 patients)
      and increased from 328+/-79 meters to 353+/-66 meters in the placebo group (10
      patients) (P=0.142). Resting oxygen saturation by pulse oximetry changed from
      87+/-4% to 85+/-14% in the Pentoxifylline group and from 88+/-3% to 88+/-2% in
      the placebo group (P=0.676). There were no significant changes in dyspnea
      severity index and heart rate before and after the 6MWT. CONCLUSION:
      Pentoxifylline does not seem to improve exercise capacity and dyspnea in patients
      with severe and very severe COPD.

PMID- 24031107
TI  - Clinical characteristics of pediatric esophagitis in southern iran; a single
      center experience.
AB  - BACKGROUND: We sought to determine the clinical characteristics of pediatric
      esophagitis in southern Iran. METHODS: This cross-sectional study was conducted
      over a 4-year period, from 2005 to 2009, in Nemazee Hospital, a tertiary
      healthcare center in Shiraz, southern Iran. We consecutively included all
      pediatric patients (<18 years) who underwent endoscopy in our center and had
      pathology-confirmed diagnosis of esophagitis. Data regarding the patients'
      demographic characteristics, comorbidities, and clinical findings were recorded
      using a questionnaire. All the patients underwent upper gastrointestinal
      endoscopy and biopsy of the esophagus, and the findings were recorded in the
      questionnaire. RESULTS: We studied 125 children, comprising 61 (48.8%) girls and
      64 (51.2%) boys at a mean age of 6.6+/-5.5 years. Repeated vomiting was the
      prominent symptom in our series, with it being reported by 75 (60%) patients,
      followed by fever in 35 (28%). Erythema (33.6%), esophageal ulcer (11.2%), and
      whitish patch (8.0%) were the most common endoscopic findings, while reflux
      esophagitis (32.8%), chronic (6.4%) and acute esophagitis (5.6%), and candida
      esophagitis (5.6%) were the most common histological diagnoses. Only one (0.8%)
      patient was diagnosed as having eosinophilic esophagitis, aspergillosis, and
      graft-versus-host disease. CONCLUSION: Reflux was the most common cause of
      esophagitis in the pediatric population of southern Iran. Contrary to previous
      reports, the prevalence of eosinophilic esophagitis was far less than that
      estimated, while the prevalence of opportunistic infections was higher secondary
      to post-liver transplantation immunosuppression.

PMID- 24031108
TI  - Cardiovascular Responses during Head-Down Crooked Kneeling Position Assumed in
      Muslim Prayers.
AB  - BACKGROUND: Movement dysfunction may be expressed in terms of symptoms
      experienced in non-physiological postures, and head-down crooked kneeling (HDCK)
      is a posture frequently assumed by Muslims during prayer activities. The purpose
      of this study was to investigate the cardiovascular responses in the HDCK
      posture. METHODS: Seventy healthy volunteers, comprising 35 males and 35 females,
      participated in the study. Cardiovascular parameters of blood pressure and pulse
      rate of the participants were measured in rested sitting position and then at one
      and three minutes into the HDCK posture. Two-way ANOVA was used to determine the
      differences between cardiovascular responses at rest and in the HDCK posture, and
      the Student t test was utilized to determine gender difference in cardiovascular
      responses at rest and at one and three minutes into the HDCK posture. RESULTS:
      The study showed a significant decrease in systolic and diastolic blood pressures
      at one minute into the HDCK posture and an increase in pulse rate at one and
      three minutes into the HDCK posture, as compared to the resting values. Rate
      pressure product also rose at one minute into the HDCK posture, whereas pulse
      pressure increased at one and three minutes into the HDCK posture, as compared
      with the resting values. However, no significant change was observed in the mean
      arterial pressure values. CONCLUSION: The findings from this study suggest that
      no adverse cardiovascular event can be expected to occur for the normal duration
      of this posture during Muslim prayer activities.

PMID- 24031109
TI  - Antibacterial Activity of Thymus Syriacus Boiss Essential Oil and Its Components
      against Some Syrian Gram-Negative Bacteria Isolates.
AB  - BACKGROUND: Despite the medical discoveries of different medicines and advanced
      ways of treatment, statistics have shown that the number of patients is
      increasing. This may be due to chemical drugs used in healthcare, agriculture,
      and diets. This soaring demand in medicines urges us to look for natural sources
      such as aromatic plants and essential oils, which are rich in efficient
      compounds. METHODS: Extraction of essential oils was performed using a Clevenger
      type apparatus. Identification was achieved using the GC-FID technique.
      Confirmation was made using the GC-MS technique, and isolation was done using a
      preparative HPLC, equipped with an aliquots collector. The microdilution broth
      susceptibility assay was utilized to determine minimum inhibitory concentrations
      (MICs). RESULTS: Our in vitro study demonstrated the antibacterial activity of
      the Thymus syriacus Boiss essential oil and its components against the tested
      isolates at levels between 0.375 and 50 ul/ml. The main components of the T.
      syriacus essential oil were carvacrol, gamma-terpinene, and beta-caryophyllene.
      MIC90 values for the T. syriacus essential oil against the gram-negative
      organisms varied between 3.125 and 12.5 ul/ml. The most effective components
      against the gram-negative bacteria were thymol, carvacrol, dihydro-carvon, and
      linalool respectively. CONCLUSIONS: The T. syriacus essential oil and some of its
      components exhibited very good inhibitory effects against Syrian gram-negative
      isolates.

PMID- 24031110
TI  - Anti-Nuclear Antibodies in Patients with Polycystic Ovary Syndrome before and
      after Laparoscopic Electrocauterization.
AB  - Polycystic ovary syndrome (PCOS) has been suggested to be linked with autoimmune
      processes. Laparoscopic ovarian electrocauterization has the potency to stimulate
      more autoimmune reactions in PCOS patients. In the present study, we considered
      anti-nuclear antibodies (ANAs) as the hallmark of autoimmune reactions, and
      investigated the serum level of these antibodies in 35 patients with PCOS (21-38
      years old) pre and one-month after electrocauterization, and in 35 fertile
      healthy women (25-35 years old) as the control group. Serum levels of ANAs, as
      well as ANA subtyping, were investigated using the Enzyme-Linked Immunosorbent
      Assay (ELISA). While 3 out of the 35 patients (8.6%) were positive for ANAs
      before electrocauterization, none of the controls was positive. The number of ANA
      positive cases increased following electrocauterization (3 out of 35 [8.6%]
      before vs. 10 out of 35 [28.6%] after the procedure). The main ANA subtype in the
      positive samples was SS-A. The higher ANA level among the PCOS patients suggests
      association of the disease with autoimmune reactions. Laparoscopic ovarian
      electrocauterization seems to increase the number of positive-ANA patients. 

PMID- 24031111
TI  - MSX1 mutation in witkop syndrome; a case report.
AB  - The Witkop syndrome is a rare autosomal dominant disorder characterized by the
      absence of several teeth and abnormalities of the nails. This is the first report
      of a rare genetic tooth and nail syndrome diagnosed in a 2.5-year-old boy with
      early exfoliation of the primary canine, absence of the primary incisors, and
      nail dysplasia. A homozygous mutation was identified in 3'-UTR of MSX1 gene in
      the proband. The parents of the patient had no dental and nail anomalies. 

PMID- 24031112
TI  - Reactivation of cytomegalovirus in a patient with stevens-johnson syndrome-toxic
      epidermal necrolysis.
AB  - Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe
      adverse cutaneous reactions to drugs. We describe the case of a 19 year old
      patient with SJS/TEN overlap syndrome, who developed severe interstitial
      pneumonia after she had received antiepileptic drugs. A cytomegalovirus infection
      was diagnosed by Real Time Polymerase Chain Reaction (RT-PCR) detection on
      Bronchoalveolar lavage. Based on observations on biological data, temporal
      relationship, and clinical features, it could be inferred that the reactivation
      of cytomegalovirus with viral replication can predispose a person to TEN-SJS. We
      discuss here, in the light of the current literature, the probable association
      between drug-induced SJS-TEN and fulminant reactivation of cytomegalovirus. 

PMID- 24031113
TI  - Pyrexia in a patient with megaloblastic anemia: a case report and literature
      review.
AB  - Deficiency of vitamin B12 and/or folic acid as a cause of pyrexia, though known,
      is rarely reported in literature. We aimed to report a case in a 51 year old
      woman, who presented with fever and pancytopenia and was diagnosed to have
      megaloblastic anemia secondary to vitamin B12 and folate deficiency. The pyrexia
      subsided following the intramuscular injection of vitamin B12 and oral folic acid
      administration. All the other infective, inflammatory/autoimmune, endocrine
      causes of pyrexia were excluded by appropriate investigations. Therefore, we
      suggest that all physicians be aware of megaloblastic anemia as a treatable cause
      of pyrexia in order to avoid unnecessary costly investigations and antibiotic
      usage. 

PMID- 24031114
TI  - Cultural differences and importance of somatic symptoms could provide hidden
      clues and potential management options for depressed patients with suicidal
      ideation.

PMID- 24031115
TI  - Modeling the measurements of cellular fluxes in microbioreactor devices using
      thin enzyme electrodes.
AB  - An analytic approach to the modeling of stop-flow amperometric measurements of
      cellular metabolism with thin glucose oxidase and lactate oxidase electrodes
      would provide a mechanistic understanding of the various factors that affect the
      measured signals. We divide the problem into two parts: (1) analytic formulas
      that provide the boundary conditions for the substrate and the hydrogen peroxide
      at the outer surface of the enzyme electrode layers and the electrode current
      expressed through these boundary conditions, and (2) a simple diffusion problem
      in the liquid compartment with the provided boundary conditions, which can be
      solved analytically or numerically, depending on the geometry of the compartment.
      The current in an amperometric stop-flow measurement of cellular glucose or
      lactate consumption/excretion is obtained analytically for two geometries,
      corresponding to devices developed at the Vanderbilt Institute for Integrative
      Biosystems Research and Education: a multianalyte nanophysiometer with effective
      one-dimensional diffusion and a multianalyte microphysiometer, for which
      plentiful data for metabolic changes in cells are available. The data are
      calibrated and fitted with the obtained time dependences to extract several
      cellular fluxes. We conclude that the analytical approach is applicable to a wide
      variety of measurement geometries and flow protocols.

PMID- 24031116
TI  - Neural Basis of Action Understanding: Evidence from Sign Language Aphasia.
AB  - BACKGROUND: The neural basis of action understanding is a hotly debated issue.
      The mirror neuron account holds that motor simulation in fronto-parietal circuits
      is critical to action understanding including speech comprehension, while others
      emphasize the ventral stream in the temporal lobe. Evidence from speech strongly
      supports the ventral stream account, but on the other hand, evidence from manual
      gesture comprehension (e.g., in limb apraxia) has led to contradictory findings.
      AIMS: Here we present a lesion analysis of sign language comprehension. Sign
      language is an excellent model for studying mirror system function in that it
      bridges the gap between the visual-manual system in which mirror neurons are best
      characterized and language systems which have represented a theoretical target of
      mirror neuron research. METHODS & PROCEDURES: Twenty-one life long deaf signers
      with focal cortical lesions performed two tasks: one involving the comprehension
      of individual signs and the other involving comprehension of signed sentences
      (commands). Participants' lesions, as indicated on MRI or CT scans, were mapped
      onto a template brain to explore the relationship between lesion location and
      sign comprehension measures. OUTCOMES & RESULTS: Single sign comprehension was
      not significantly affected by left hemisphere damage. Sentence sign comprehension
      impairments were associated with left temporal-parietal damage. We found that
      damage to mirror system related regions in the left frontal lobe were not
      associated with deficits on either of these comprehension tasks. CONCLUSIONS: We
      conclude that the mirror system is not critically involved in action
      understanding.

PMID- 24031117
TI  - In-hive patterns of temporal polyethism in strains of honey bees (Apis mellifera)
      with distinct genetic backgrounds.
AB  - Honey bee workers exhibit an age-based division of labor (temporal polyethism,
      DOL). Younger bees transition through sets of tasks within the nest; older bees
      forage outside. Components of temporal polyethism remain unrevealed. Here, we
      investigate the timing and pattern of pre-foraging behavior in distinct strains
      of bees to (1) determine if a general pattern of temporal DOL exists in honey
      bees, (2) to demonstrate a direct genetic impact on temporal pacing, and (3) to
      further elucidate the mechanisms controlling foraging initiation. Honey bees
      selected for differences in stored pollen demonstrate consistent differences in
      foraging initiation age. Those selected for increased pollen storage (high pollen
      hoarding strain, HSBs) initiate foraging earlier in life than those selected for
      decreased pollen storage (low pollen hoarding strain, LSBs). We found that HSBs
      both initiate and terminate individual pre-foraging tasks earlier than LSBs when
      housed in a common hive environment. Unselected commercial bees (wild type)
      generally demonstrated intermediate behavioral timing. There were few differences
      between genotypes for the proportion of pre-foraging effort dedicated to
      individual tasks, though total pre-foraging effort differences differed
      dramatically. This demonstrates that behavioral pacing can be accelerated or
      slowed, but the pattern of behavior is not fundamentally altered, suggesting a
      general pattern of temporal behavior in honey bees. This also demonstrates direct
      genetic control of temporal pacing. Finally, our results suggest that earlier HSB
      protein (pollen) consumption termination compared to LSBs may contribute to an
      earlier decline in hemolymph vitellogenin protein titers, which would explain
      their earlier onset of foraging.

PMID- 24031118
TI  - Correlates of African American Men's Sexual Schemas.
AB  - Sexual schemas are cognitive representations of oneself as a sexual being and aid
      in the processing of sexually relevant information. We examined the relationship
      between sociosexuality (attitudes about casual sex), masculine ideology
      (attitudes toward traditional men and male roles), and cultural centrality
      (strength of identity with racial group) as significant psychosocial and
      sociocultural predictors in shaping young, heterosexual African American men's
      sexual schemas. A community sample (n=133) of men in a southeastern city of the
      United States completed quantitative self-report measures examining their
      attitudes and behavior related to casual sex, beliefs about masculinity, racial
      and cultural identity, and self-views of various sexual aspects of themselves.
      Results indicated that masculine ideology and cultural centrality were both
      positively related to men's sexual schemas. Cultural centrality explained 12 % of
      the variance in level of sexual schema, and had the strongest correlation of the
      predictor variables with sexual schema (r=.36). The need for more attention to
      the bidirectional relationships between masculinity, racial/cultural identity,
      and sexual schemas in prevention, intervention, and public health efforts for
      African American men is discussed.

PMID- 24031119
TI  - Current perception threshold for assessment of the neurological components of
      hand-arm vibration syndrome: a review.
AB  - Current perception threshold (CPT) has been proposed as a quantitative method for
      assessment of peripheral sensory nerve function. The aim of this review of
      selected reports is to provide an overview of CPT measurement for the assessment
      of the neurological component of hand-arm vibration syndrome (HAVS). The CPT
      values at 2000 Hz significantly increased for patients with HAVS. This result
      supports the previous histological findings that demyelination is found
      predominantly in the peripheral nerves in the hands of men exposed to hand-arm
      vibration. Diagnostic sensitivity and specificity were high for severe cases of
      Stockholm sensorineural (SSN) stage 3 compared with non-exposed controls, but not
      high for mild cases of SSN stage 1 or 2 and for carpal tunnel syndrome associated
      with HAVS. However, there are only a few studies on the diagnostic validity of
      the CPT test for the neurological components of HAVS. Further research is needed
      and should include diagnostic validity and standardizing of measurement
      conditions such as skin temperature. 

PMID- 24031120
TI  - Tubular-trabecular type Basal cell adenoma of the parotid gland: a patient
      report.
AB  - Basal cell adenoma (BCA) is an uncommon benign salivary gland neoplasm that
      includes isomorphic basaloid cells. We report on a female patient with BCA that
      developed in the right parotid gland in her 50s. The present patient demonstrated
      a few tumor nests in the fibrous capsule, and her tumor was larger than usual.
      These facts made us suspect of malignancy. Histopathologically, the tumor was
      characterized by multiple duct-like structures and tubular-trabecular masses
      composed of small isomorphic cells with hyperchromatic, round nuclei and an
      eosinophilic cytoplasm. It was difficult to determine whether the ductal
      structures noted in the tumor capsule were invasive. By immunohistochemistry,
      tumor cells of the tubular nests were positive for cytokeratin 7 and that the
      outer cells of tubular nests were positive for alpha smooth muscle actin
      (alphaSMA) and calponin. Tumor cells were immuno-negative for S-100 protein and
      glial fibrillary acidic protein. The Ki-67 labeling scores of the cells were
      extremely low (< 1%). We could achieve an accurate diagnosis of BCA by
      immunohistochemistry with MIB-1 and other markers. 

PMID- 24031121
TI  - ACTH-Producing Breast Cancer: A Patient Report.
AB  - Ectopic ACTH secretion in the setting of breast cancer is extremely rare but when
      present affects both the tumor's behavior and the incidence of complications. The
      patient, a 58-year-old woman, first presented with a mass in her left breast as
      well as multiple osseous metastases and a right femur fracture. Laboratory data
      revealed a hypokalemic alkalosis. Her plasma ACTH level was elevated. She was
      diagnosed with breast cancer with ectopic ACTH secretion, and underwent a left
      mastectomy and axillary lymph node dissection. Histological examination
      demonstrated a poorly differentiated neuroendocrine carcinoma with ectopic ACTH
      secretion. Although the signs and symptoms of ectopic ACTH secretion from a
      breast cancer are frequently subtle, the recognition of ectopic ACTH secretion
      from breast cancer is important for patient management. 

PMID- 24031122
TI  - Thoracoscopic resections of bronchogenic cysts arising in the posterior
      mediastinum: a report on 3 patients.
AB  - We report 3 cases of patients with bronchogenic cyst arising in the posterior
      mediastinum. The patients were a 19-year-old male, a 36-year-old female and a 33
      year-old female, whose cysts were detected as abnormal shadows in the chest. In 2
      of them, neurogenic tumors were suspected preoperatively. We performed
      thoracoscopic resection for the 3 tumors. Bronchogenic cysts may occur
      ectopically, and the posterior mediastinum must be sufficiently recognized as a
      rare but possible ectopic site. 

PMID- 24031123
TI  - Increased B7-H1 and B7-H4 Expressions on Circulating Monocytes and Tumor
      Associated Macrophages are Involved in Immune Evasion in Patients with Gastric
      Cancer.
AB  - Expression of the costimulatory molecule B7-H4, a member of the inhibitory B7
      family, has been reported to be upregulated on tumor-associated macrophages, and
      this overexpression may be involved in immune evasion in cancer patients. The
      present study was designed to investigate B7-H4 expression on
      monocytes/macrophages and its relationship with immune evasion in gastric cancer
      patients. B7-H4 expression on circulating monocytes and tumor-associated
      macrophages was evaluated by multicolor flow cytometry. Carboxyfluorescein
      succinimidyl ester proliferation assays and quantitative interferon-gamma enzyme
      linked immunosorbent assays were carried out to determine the inhibitory effect
      of B7-H4+ monocytes on CD4+ T cells. B7-H4 expression on circulating monocytes
      was upregulated and these B7-H4+ monocytes showed immunosuppressive properties.
      B7-H4 expression was closely related to the depth of invasion, as well as the
      presence of lymphatic and venous invasion. There were significant correlations
      between B7-H4 expression and B7-H1 or HLA-DR expression on monocytes/macrophages
      in gastric cancer patients. B7-H4 expression was remarkably upregulated in
      gastric cancer tissues compared with peripheral blood samples. Complete surgical
      removal of the tumor decreased B7-H4 expression on circulating monocytes from
      gastric cancer patients. Cocultures of gastric cancer cell lines and monocytes
      led to upregulation of B7-H4 expression on monocytes. Increased B7-H4 expression
      on circulating monocytes and tumor-associated macrophages may be one of the key
      mechanisms responsible for immune evasion by tumors in gastric cancer. 

PMID- 24031124
TI  - Protective Effects of Ginger against Aspirin-Induced Gastric Ulcers in Rats.
AB  - We investigated the mechanism underlying the protective effects of ginger against
      gastric damage induced by aspirin in rats. Gastric mucosal lesions were produced
      by orally administering 200 mg/kg aspirin suspended in 1% carboxymethylcellulose
      solution to pyloric-ligated male Wistar rats. Ginger powder (200 mg/kg) markedly
      reduced the aspirin-induced gastric hemorrhagic ulcer area. The total acidity of
      gastric juice was not significantly influenced by aspirin or ginger. Ginger
      powder did not affect the aspirin-induced reduction in mucosal prostaglandin E2
      (PGE2) content; however, it did ameliorate the aspirin-induced increases in
      mucosal activity of the inducible form of NO synthase (iNOS) and plasma tumor
      necrosis factor (TNF)-alpha and interleukin (IL)-1beta levels. In the next
      experiment, high and low doses of 6-gingerol and 6-shogaol were used instead of
      ginger powder in the same experimental model to examine their roles in the anti
      ulcer mechanism of ginger. Both 6-gingerol and 6-shogaol reduced aspirin induced
      ulcer formation, mucosal iNOS and plasma TNF-alpha and IL-1beta levels. In
      conclusion, ginger powder prevents the aspirin induced gastric ulcer formation by
      reducing mucosal iNOS activity and the plasma levels of inflammatory cytokines
      but does not affect gastric juice or acid production or mucosal PGE2 content.
      This protective effect of ginger powder against gastric ulcers may be
      attributable to both gingerol and shogaol. 

PMID- 24031125
TI  - Application of a bacterial artificial chromosome modification system for a human
      artificial chromosome vector.
AB  - Exactly controlled conditional gene expressing systems are crucial for genomic
      functional research, animal transgenesis and gene therapy. Bacterial artificial
      chromosomes (BACs) are optimal for harboring long fragments of genomic DNA or
      large cDNA up to 300 kb in size. Therefore, BACs are available to produce
      transgenic cells and animals for the functional studies of genes. However, BAC
      can insert DNA randomly into the host genome, possibly causing unpredicted
      expression. We previously developed a human artificial chromosome (HAC) vector
      from human chromosome 21 using chromosome engineering. The HAC vector has several
      important characteristics desired for an ideal gene delivery vector, including
      stable episomal maintenance, and the ability to carry large genomic DNA
      containing its own regulatory element, thus allowing physiological regulation of
      the transgene in a manner similar to that of the native chromosome. In this
      study, we develop a system fusing BAC library and HAC technology together to
      allow tight control of gene expression. This system enables BAC to be cloned into
      the defined locus on the HAC vector by the Cre/loxP system. In addition, the
      genome in the BAC is possible to be engineered freely by the BAC recombineering
      technology. This system is a highly efficient tool for the rapid generation of
      stringently controlled gene expression system on the HAC vector. 

PMID- 24031126
TI  - Squamous cell carcinoma derived from a skin flap used for reconstruction of the
      hypopharynx.
AB  - Development of a secondary primary cancer in a skin flap is a rare complication.
      A 70-year-old man underwent partial laryngopharyngectomy, right neck dissection
      and reconstruction with a radial forearm free flap in 2004. Five years later, an
      exophytic tumor was found on the hypopharynx reconstructed with the radial
      forearm free flap. He underwent total laryngopharyngectomy, left neck dissection
      and reconstruction with a jejunal free flap in June 2009. Pathological findings
      suggested this was a primary cancer rather than a metastasis. Localization to the
      epidermis and dermis indicate that the tumor was derived from the surface of the
      skin flap. 

PMID- 24031127
TI  - Current duty arrangements and circumstances of emergency medical technicians:
      findings of an electronic questionnaire survey conducted at the 16th national
      ambulance-crew symposium.
AB  - To assess the working arrangements and effects on the health of medical emergency
      transport personnel, we conducted an electronic questionnaire survey among
      participants of the 16th National Ambulance-Crew Symposium in 2008. Answers were
      obtained from 58 participants (56 males, 2 females): 58 questionnaires were fully
      completed and suitable for analysis. Of the 58, 47 respondents were emergency
      medical technicians (including those with additional roles). In the analysis of
      the responses, we observed a negative correlation between the number of emergency
      transport dispatches (in 1 day) and total nap time, and between the number of
      night emergency transports per shift and quality of sleep. These findings
      suggested that an increase in the number of emergency transports was associated
      with a decrease in nap time and sleep quality. 

PMID- 24031128
TI  - Pandemic influenza: a never-ending story.
AB  - A novel pandemic influenza emerged in 2009, something that hasn't been seen since
      1977. The following issues will be introduced and discussed in this review: the
      history of influenza pandemics, the emergence of the novel pandemic influenza of
      2009, epidemics in the southern and northern hemispheres after the recognition of
      index cases in the United States, mortality, viral characteristics, prevention in
      the household setting, clinical aspects, diagnosis, treatment and immunization.
      Some questions have been answered. However, a number of other questions remain.
      Scientific research must follow up on these unanswered questions. 

PMID- 24031129
TI  - The Effects of Olmesartan and Alfacalcidol on Renoprotection and klotho Gene
      Expression in 5/6 Nephrectomized Spontaneously Hypertensive Rats.
AB  - Recently, an angiotensin inhibitor has been shown to upregulate the klotho mRNA
      level in chronic renal failure. In addition, the administration of vitamin D has
      been reported to improve the mortality of patients with chronic renal failure. In
      this study, we examined the effects of an angiotensin inhibitor and/or vitamin D
      on the progression of chronic renal failure by using male 5/6 nephrectomized
      (5/6Nx) spontaneously hypertensive rats. Male 5/6Nx spontaneously hypertensive
      rats were assigned to 4 groups as follows: 5/6Nx group, 5/6Nx rats; Alf group,
      5/6Nx rats administered alfacalcidol (0.2 MUg/kg/day); Olm group, 5/6Nx rats
      administered olmesartan (15 mg/kg/day); Alf + Olm group, 5/6Nx rats administered
      alfacalcidol (0.2 MUg/kg/day) and olmesartan (15 mg/kg/day). These drugs were
      administered for 12 weeks. Systolic blood pressure in the Alf, Olm and Alf + Olm
      groups were significantly decreased relative to that in the 5/6Nx group during
      the 12-week experimental period. As a result, all treated groups showed
      renoprotection based on improvement of the systolic blood pressure, urinary
      protein excretion and histological renal fibrosis. Combination therapy of
      alfacalcidol and olmesartan was more effective than either alfacalcidol or
      olmesartan alone. Expression of klotho mRNA was significantly upregulated in the
      Alf + Olm group in comparison with in the 5/6Nx group. Serum levels of fibroblast
      growth factor 23 in the Alf group and the Alf + Olm group were significantly
      higher than those in the 5/6Nx group and the Olm group. In conclusion, the
      combination of Olm and Alf inhibited the progression of renal damage in the 5/6Nx
      group through the strong antihypertensive effect as well as the upregulation of
      the klotho gene. 

PMID- 24031130
TI  - Operative Procedure for Laparoscopy-Assisted Vagus Nerve and Pylorus-Preserving
      Gastrectomy (LAVNPPG) for Early Gastric Cancer.
AB  - Laparosocpy-assisted pylorus-preserving gastrectomy (LAPPG) is a widely accepted
      surgical procedure for the treatment of early gastric cancer in the middle third
      of the stomach. We have been performing this operation since 2007. Compared with
      traditional distal gastrectomy, LAPPG has postoperative nutritional benefits for
      patients. However, this procedure preserves only the pyloric branch of the vagus
      nerve and not the celiac branch. We found that patients retain a large amount of
      residual food in the gastric remnant, which interferes with the detection of
      secondary cancer on endoscopic follow-up. To improve the pyloric function and
      postoperative gastrointestinal motility, we changed our procedure during 2009 to
      preserve both the pyloric and celiac branches of the vagus nerve, and we named
      this new procedure laparoscopy-assisted vagus nerve and pylorus-preserving
      gastrectomy (LAVNPPG). From 2009 to 2011, 11 patients underwent LAVNPPG at our
      hospital. Retrospective comparison of the safety of operation, postoperative
      complications, and condition of the gastric remnant between LAPPG (n = 13) and
      LAVNPPG (n = 11) found that the occurrence of postprandial stasis and food
      residue in the gastric remnant tended to be lower following LAVNPPG, though the
      differences were not significant. These findings indicate that LAVNPPG may be an
      operative procedure that could replace LAPPG. 

PMID- 24031131
TI  - Psychological Factors and Characteristics of Recurrent Breast Cancer Patients
      with or without Psychosocial Group Therapy Intervention.
AB  - To clarify psychological factors of patients with recurrent breast cancer, we
      examined their interest in group intervention and studied the characteristics of
      participants and non-participants in an intervention program. Using several self
      administered assessment scales to evaluate the quality of life (QOL) of cancer
      patients and the symptoms specific to breast cancer patients, we compared
      sociomedical variables and QOL scores between participants and non-participants.
      Inter-group differences were significant in the scores for constipation, body
      image and future perspectives, suggesting the QOL to be higher among participants
      than non-participants. Interest in group intervention was identified as a major
      reason for participation in this type of program. Not only physical but also
      psychologicalfactors were shown to be the reasons for deciding not to participate
      in group intervention. It is now desirable that efforts be made to stimulate
      greater understanding of group intervention as a means of psychosocial support
      for patients with recurrent breast cancer and that social environments be
      arranged so that these patients are supported by an approach tailored to
      individual cases, involving both group and individual intervention. 

PMID- 24031132
TI  - Detection of pneumothorax visualized by computer analysis of bilateral
      respiratory sounds.
AB  - Pneumothorax is usually diagnosed based on the attenuation of respiratory sounds
      of the affected side on auscultation, but it requires a skilled technique and is
      limited to subjective evaluation. Thus, we designed a device which analyzes and
      converts the frequency of auscultatory sounds to numerical values with a
      computer. With this device, the bilateral sound pressure levels were compared
      between groups of 25 healthy subjects and 21 patients with pneumothorax to
      investigate the efficacy of the diagnosing tool of pneumothorax. While recording
      respiratory sounds of the bilateral precordial regions, the fast Fourier
      transform was applied with a frequency analysis software, power spectra of the
      auscultatory sounds were displayed in real-time, and the sound pressure level was
      compared between the bilateral sides. The difference was investigated at
      frequencies judged as less likely to be influenced by cardiac sounds (200-400
      Hz). No difference was observed in the control group (n = 25, P > 0.05), but
      respiratory sound attenuation was detectable on the affected side in the
      pneumothorax group (n = 21, P < 0.01 each for the paired Student's t-test and
      Wilcoxon signed-rank test). When the cutoff value was 8 dB, the sensitivity and
      specificity as diagnostic tool of pneumothorax was 71.4% and 100%, respectively.
      This device would facilitate the detection of occult pneumothorax at accident
      scenes, in emergency rooms and in intensive care units. 

PMID- 24031133
TI  - Mediastinal malignant lymphoma difficult to diagnose: a patient report.
AB  - We report a 58-year-old man who suffered from shortness of breath on exertion
      with wheezing. A chest enhanced computed tomography (CT) scan showed an irregular
      tumor in the middle mediastinum involving the right main pulmonary artery, vena
      cava superior and right main bronchus. Transbronchial lung biopsy and
      endobronchial ultrasound-guided transbronchial needle aspiration yielded no
      evidence for a pathological diagnosis of malignancy. We employed mediastinoscopy,
      which led to a diagnosis of lymphoid reactive change. 18F-fluorodeoxyglucose
      positron emission tomography (FDG-PET) scan revealed a high FDG uptake in the
      tumor lesion. Because the CT scan and FDG-PET findings led to a marked suspicion
      of malignancy, we decided to attempt biopsy by a video-assisted thoracoscopic
      surgery (VATS) approach. Flow cytometry showed a monoclonal pattern, and the
      final diagnosis was mediastinal follicular lymphoma both pathologically and
      immunohistologically. The patient achieved a complete remission by following
      chemotherapy. Low-grade malignancy type of lymphoma such as follicular lymphoma
      that generally contains small-cell components often presents a diagnostic
      challenge and the VATS approach was effective for the diagnosis of such type of
      mediastinal lymphoma. 

PMID- 24031134
TI  - Upregulation of TIM-3 and PD-1 on CD4+ and CD8+ T Cells Associated with
      Dysfunction of Cell-Mediated Immunity after Colorectal Cancer Operation.
AB  - Surgery has been reported to suppress cell-mediated immunity; however, the
      detailed mechanisms responsible for this remain unclear. We obtained information
      on expressions of T-cell immunoglobulin domain and mucin domain 3 (TIM-3) and
      programmed cell death 1 (PD-1) on both CD4+ and CD8+ T cells postoperatively from
      colorectal cancer patients and evaluated by multicolor flow cytometry. The
      functions of CD4+ and CD8+ T cells based on TIM-3 and PD-1 expressions were
      determined by quantitating the concentration of interferon-gamma (IFN-gamma) by
      enzyme-linked immunosorbent assay. The study demonstrated a rapid and significant
      decrease in number of total lymphocytes, CD4+ T cells and CD8+ T cells. These
      immune cells reached the minimum on day 1 and then increased, but still
      significantly decreased on days 3 and 7. The frequency of PD-1+CD4+ T cells and
      TIM-3+CD4+ T cells significantly increased after colorectal surgery. IFN-gamma
      secretion by PD-1+TIM-3+CD4+ T cells was significantly decreased compared to
      secretion by either PD-1+TIM3-CD4+ T cells or PD-1-TIM-3-CD4+ T cells.
      Furthermore, IFN-gamma secretion by PD-1+TIM-3+CD8+ T cells was significantly
      decreased compared to secretion by either PD-1-TIM-3+CD8+ T cells or PD-1-TIM-3
      CD8+ T cells. The expression of PD-1 and TIM-3 was closely related to impaired
      cell-mediated immunity that was observed after surgery for colorectal cancer. New
      treatment targeting TIM-3 and PD-1 on CD4+ and CD8+ T cells during the
      perioperative period may provide a breakthrough in the treatment of colorectal
      cancer patients. 

PMID- 24031135
TI  - Mechanisms underlying production and externalization of oxidized
      phosphatidylserine in apoptosis: involvement of mitochondria.
AB  - The present study was performed by using selective inhibitors of caspase-8 and
      caspase-3 functioning upstream and downstream from mitochondria, respectively to
      determine whether mitochondria are involved in the mechanisms underlying
      production and externalization of oxidized phosphatidylserine (PSox) during Fas
      mediated apoptosis. Treatment with anti-Fas antibody induced caspase-3
      activation, chromatin condensation, release of cytochrome c (cyt c) from
      mitochondria into the cytosol as well as production of PSox and its exposure to
      the cell surface in Jurkat cells. Inhibition of caspase-8 by pretreatment with Z
      IETD-FMK, a membrane permeable selective caspase-8 inhibitor reduced
      mitochondrial cyt c release, the amount of PSox not only within but also on the
      surface of Jurkat cells, caspase-3 activation, and apoptotic cell number after
      treatment with anti-Fas antibody. In contrast, Z-DEVD-FMK, a membrane permeable
      selective caspase-3 inhibitor was unable to inhibit cyt c release, and the amount
      of PSox both within and on the surface of the cells after anti-Fas antibody,
      although it suppressed caspase-3 activation and apoptosis. Thus, these results
      strongly suggest that mitochondria play an important role in production of PSox
      and subsequent its externalization during apoptosis. 

PMID- 24031136
TI  - Fragility fracture prevention: review from a Japanese perspective.
AB  - Osteoporosis has been named the silent disease because there are no symptoms
      until a fragility fracture occurs. With the rapid rise in the elderly population,
      the number of patients with osteoporosis and fragility fractures has increased in
      most developed countries. Fragility fractures increase societal burdens in terms
      of mortality and quality of life, as well as economic costs. Fragility fractures
      of the hip have the most impact on the ambulatory status of the elderly and its
      incidence is reported to be lower among Asians or Africans than Caucasians.
      Increases in the age-specific and gender-specific incidence of hip fracture with
      time have been reported in Asian countries, including Japan; however, studies in
      North America, Europe and Oceania have reported decreases in the incidence. A new
      fragility fracture increases fracture risk, resulting in possible recurrence or
      other new fractures. The most important strategy for preventing such fractures is
      a systematic approach to educating and following patients in the immediate
      postoperative period after the initial fragility fracture. 

PMID- 24031137
TI  - Association of gene polymorphism of the fat mass and obesity associated gene with
      metabolic syndrome: a retrospective cohort study in Japanese workers.
AB  - To investigate whether gene polymorphism of the fat mass and obesity associated
      gene (FTO) is associated with metabolic syndrome (MS), we used two MS criteria,
      the National Cholesterol Education Program-Adult Treatment panel III (NCEP
      ATPIII) definition in 2003 and the Japanese definition in 2005. Subjects were
      respectively 859 and 865 Japanese workers at a company in Shimane Prefecture,
      Japan. They were non-MS individuals in 1998 and had regular health checkups
      between 1998 and 2006. The Cox proportional hazard regression was used to predict
      MS. Three SNPs in the FTO, rs9939609, rs1121980 and rs1558902, were genotyped by
      the TaqMan PCR assay and a retrospective study was performed. The three SNPs in
      the FTO were significantly associated with body mass index, and rs1121980 and
      rs1558902 were associated with fasting plasma glucose. MS defined by the NCEP
      ATPIII definition was significantly associated with additive and dominant models
      of rs9939609 and rs1121980, and the dominant model of rs1558902, even after
      adjusting for confounding factors such as age, sex and lifestyle. MS defined by
      the Japanese definition was significantly associated with the additive model of
      rs1121980 and additive and dominant models of rs1558902 in multivariate analysis.
      These results suggested that FTO gene polymorphisms, rs9939609, rs1121980 and
      rs1558902, were associated with an increased risk of MS among Japanese workers. 

PMID- 24031138
TI  - Influence of Asian Desert Dust on Lower Respiratory Tract Symptoms in Patients
      with Asthma over 4 Years.
AB  - The Asian Dust Storm (ADS) aggravates symptoms and pulmonary dysfunction in adult
      asthma patients. Our objective was to investigate the association of air
      pollutants and metals in desert dust with worsening of asthma symptoms during the
      ADS. A telephone survey was performed to investigate the upper and lower
      respiratory tract symptoms, ocular symptoms and skin symptoms of asthma patients
      during the ADS in March between 2007 and 2010. Four surveys were conducted in 46
      patients. Two patients noted worsening of lower respiratory tract symptoms in all
      four surveys, as well as 2 patients in three surveys, 7 patients in two surveys,
      and 9 patients in one survey. There was no worsening of lower respiratory tract
      symptoms in 26 patients. In each patient, the influence of the ADS on lower
      respiratory tract symptoms varied between surveys. In 2010, the level of
      suspended particulate matter was highest in all four years, but the smallest
      number of patients noted worsening of lower respiratory tract symptoms. Among
      pollutants, only the maximum concentration of nitrogen dioxide during the ADS was
      significantly associated with the worsening of lower respiratory tract symptoms.
      The influence of the ADS on lower respiratory tract symptoms of adult asthma
      patients is variable. 

PMID- 24031139
TI  - Surgical treatment for severe heart failure: recent progress in treatment
      strategy and its present status in Japan.
AB  - Chronic intractable heart failure that is unresponsive to maximum medical therapy
      can have a wide variety of causes; these include advanced valvular diseases and
      severe myocardial ischemia, ischemic cardiomyopathy (ICM) in heart failure
      following extensive myocardial infarction, chronic heart failure due to dilated
      cardiomyopathy (DCM) in which the myocardium itself is progressively damaged or
      the acute aggravation of the latter. Heart transplantation has long been
      considered the only useful treatment for patients with heart failure due to ICM-
      and DCM-induced severe left ventricular hypofunction. However, because of the
      extremely limited number of heart transplant donors, other surgical treatments
      have also been attempted. In this communication, we provide an overview of the
      current situation with regard to left ventriculoplasty and heart
      transplantations, as well as of the treatment of severe heart failure using
      ventricular assist devices, which have recently shown remarkable progress. 

PMID- 24031140
TI  - Clinicopathologic characteristics and prognosis of gastric cancer in young
      patients.
AB  - To determine the clinicopathologic characteristics and prognosis of gastric
      cancer in young patients, a total of 1985 gastric cancer patients who had
      undergone gastrectomy at our hospital were reviewed. The male-to-female ratio was
      significantly lower in the young patients than in either the middle-aged (P <
      0.0001) or elderly patients (P < 0.0001). Undifferentiated carcinoma was observed
      more frequently in the young patients compared with either the middle-aged (P <
      0.0001) or elderly patients (P < 0.0001). Furthermore, peritoneal metastasis was
      observed more frequently in the young patients than in either the middle-aged (P
      < 0.005) or elderly patients (P < 0.005). Five-year survival rates were 61.0,
      73.6 and 68.1% in the young, middle-aged and elderly patients, respectively. The
      prognosis of the middle-aged patients was significantly better than that of
      either the young or the elderly patients (P < 0.05). Multivariate analysis
      indicated that age was an independent prognostic factor. Peritoneal recurrence
      was more frequently observed in the young patients than either the middle-aged or
      the elderly patients (P < 0.05). Gastric cancer in young patients has unique
      characteristics, namely, a predominance of female patients and a high frequency
      of undifferentiated cancer and peritoneal metastasis and recurrence. 

PMID- 24031141
TI  - Evaluation of Relationships among Occupational Stress, Alcohol Dependence and
      Other Factors in Male Personnel in a Japanese Local Fire Fighting Organization.
AB  - Recent large-scale disasters have made middle-ranked fire defense officers
      responsible for routine fire fighting activities, and a tendency of alcohol
      dependence associated with other stressful problems is noted in Japan. We
      assessed the alcohol dependence tendency with the alcohol use disorders
      identification test (AUDIT) in firefighters. Occupational stress, depression and
      other factors were evaluated with the brief job stress questionnaire, Center for
      Epidemiologic Studies depression scale, K10 and a face sheet. Subjects were 294
      male personnel in a local fire defense headquarters, and 246 of them (83.4%)
      answered effectively. Data were analyzed first with univariate analysis between
      the AUDIT score and other items, and then with multivariate analysis of the AUDIT
      score as a dependent variable and other items as independent variables. The AUDIT
      score (mean +/- SD) in the 246 respondents classified by age ranges was 7.9 +/-
      5.4 points (the lowest, 0 points; the highest, 27 points). The multivariate
      analysis showed significant correlations of the AUDIT score with the workplace
      environment (P = 0.003) and the rank of work (P = 0.019). The present survey was
      cross-sectional, and we could not clarify the subjects' past drinking states and
      applicability of the results to the whole Japan personnel. It is necessary to
      further investigate the relationship between alcoholism and depression in the
      present subjects. As a pilot study, we first clarified the state of alcohol
      dependence in personnel in a Japanese local fire fighting organization, and
      examined related factors. 

PMID- 24031142
TI  - Evaluation of an e-learning distance education system in the graduate school of
      medical sciences of tottori university.
AB  - Three years have passed since the introduction of a new e-learning system as part
      of the graduate study program in the Faculty of Medicine of Tottori University.
      To improve this system, a survey was conducted among graduate students and
      faculty members to evaluate it. The subjects of the study were 138 graduate
      students (in the doctoral programs in Medical Science, 1st- and 2nd-term doctoral
      programs in Life Science, 1st- and 2nd-term doctoral programs in the Institute of
      Regenerative Medicine and Biofunction, and Clinical Psychology) as well as 108
      faculty of the Graduate School of Medical Sciences of Tottori University.
      Graduate students reported that the e-learning education system is adequate and
      that they are satisfied to an above average level. The reasons for
      dissatisfaction with the system were roughly divided into 3 categories:
      "contents", "system" and "student reports". This e-learning system is still at an
      early stage of development, but we are pushing forward to improve this in
      anticipation of increasing the use of web learning modalities in the future. 

PMID- 24031143
TI  - A case of the bilateral duplicate palmaris longus muscles coupled with the
      palmaris profundus muscle.
AB  - The palmaris longus muscle is one of the most variable muscles in human anatomy.
      During a routine anatomical dissection for medical students at Tottori
      University, we found duplicate palmaris longus muscles in the bilateral forearms
      together with the palmaris profundus muscle in the right forearm. The bilateral
      aberrant palmaris longus muscles were observed at the ulnar side of the palmaris
      longus muscle and their distal tendons were attached to the flexor retinaculum.
      The palmaris profundus muscle found in the right forearm was located at the
      radial side of the flexor digitorum superficialis muscle. The proximal tendon was
      originated from the anterior surface in the middle of the radius, while the
      distal tendon coursed radial to the median nerve through the carpal tunnel,
      finally inserting into the distal part of the flexor retinaculum. Both the
      palmaris longus and aberrant palmaris longus muscles were innervated by the
      median nerve. The palmaris profundus muscle was presumably supplied by the median
      nerve. 

PMID- 24031144
TI  - Wart with depigmented halo and generalized vitiligo.
AB  - Depigmented haloes sometimes appear around melanocytic tumors or non-melanocytic
      tumors, but coexistence of warts and depigmented haloes is extremely rare. We
      report here an unusual case of warts accompanied by depigmented haloes and
      subsequently-triggered generalized vitiligo. A 55-year-old Japanese man presented
      with a 3-year history of brown nodules on the back, upper eyelid and dorsum of
      the left hand. Depigmented haloes appeared around the noldules and then gradually
      spread over a wide area, resulting in the development of generalized vitiligo. He
      had no history of antecedent treatment for these lesions before consultation.
      Histopathologically, the lesion showed papillomatosis and hyperkeratosis with
      lymphocytic exocytosis into the epidermis, which compatible to warts. Based on
      these clinical and histopathologic findings, a diagnosis of warts with
      depigmented halo and subsequently-triggered generalized vitiligo was made. None
      of the warts had resolved spontaneously after the appearance of haloes, and the
      depigmented haloes and generalized vitiligo remain unchanged. 

PMID- 24031145
TI  - Physical and mental factors associated with obesity in individuals with mental
      disorders attending psychiatric day-care facilities.
AB  - BACKGROUND: Individuals with mental disorders have increased rates of obesity and
      metabolic syndrome. Here we evaluated factors influencing obesity in individuals
      with mental disorders who were attending psychiatric day-care facilities on an
      outpatient basis. METHODS: The subjects (n = 108) were outpatients attending
      hospital-based rehabilitation programs. We assessed body fat, weight, height,
      waist circumference, body mass index (BMI), blood pressure, Geriatric Depression
      Scale-15 (GDS) scores, frequency of day-care visits, satisfaction with body
      shape, physical comorbidity and lifestyle habits. Lifestyle habits were evaluated
      using Breslow's health index based on health-related choices. RESULTS: The
      subjects were divided into 2 groups: obese group (BMI >= 25 kg/m(2)) and non
      obese group (BMI < 25 kg/m(2)). The physical parameters and attributes of both
      groups were compared, and factors related to BMI were statistically analyzed. The
      prevalence of obesity was 47.2% in all patients, 42.4% in males and 54.8% in
      females. Weight, waist circumference, body fat and systolic and diastolic blood
      pressure were significantly higher in the obese group than in the non-obese
      group. Body fat, waist circumference, systolic blood pressure and diastolic blood
      pressure exhibited significant positive correlations with BMI, whereas the
      frequency of day-care visits, satisfaction with body shape, GDS score and
      Breslow's health index exhibited significant negative correlations with BMI.
      CONCLUSION: The present results showed that the prevalence of obesity was high in
      outpatients with mental disorders. Improvement in lifestyle choices is necessary
      to prevent obesity and the onset of metabolic syndrome in such patients.

PMID- 24031146
TI  - Radiation-induced microbleeds after cranial irradiation: evaluation by phase
      sensitive magnetic resonance imaging with 3.0 tesla.
AB  - BACKGROUND: Although there are many reports regarding radiation-induced
      microbleeds, its frequency, relation to dose and latency after radiation are not
      fully elucidated. The purpose of this study was to evaluate the frequency,
      latency, patient factors and dose relation of radiation-induced microbleeds after
      cranial irradiation using phase-sensitive magnetic resonance imaging (PSI) at 3.0
      T. METHODS: Retrospective evaluation of 34 patients (age range, 13-78 years;
      mean, 49 years; follow-up period, 3-169 months; mean 29 months) who had undergone
      cranial irradiation using magnetic resonance (MR) imaging including PSI was
      performed. Twenty-three patients received high-dose irradiation (44-60 Gy), and
      11 patients received 24-30 Gy whole brain irradiation. When microbleeds were
      detected on MR imaging in these high-dose irradiation patients, dose distribution
      maps were reproduced by reviewing the clinical records. Then the irradiated areas
      were divided into 6 radiation-dose classes: regions > 55 Gy, 45-55 Gy, 35-45 Gy,
      25-35 Gy, 15-25 Gy and 5-15 Gy. The frequency of microbleeds in each radiation
      dose class was analyzed. RESULTS: Microbleeds were detected in 7 (21%) of 34
      patients on T2-weighted imaging, whereas they were detected in 16 (47%) of the 34
      patients on PSIs. The frequency of microbleeds was higher than previously
      reported. The latency of radiation-induced microbleeds after radiation was 3
      months to 9 years (mean, 33 months). In high-dose irradiation patients, the
      frequency of microbleeds significantly was associated with radiation dose. There
      were no foci that were observed in regions that had received < 25 Gy. CONCLUSION:
      Radiation-induced microbleeds occurred more frequently in the present study than
      has been previously reported. PSI can be used to detect these vascular changes
      earlier than other conventional MR imaging techniques.

PMID- 24031147
TI  - Etanercept Promotes Bone Formation via Suppression of Dickkopf-1 Expression in
      Rats with Collagen-Induced Arthritis.
AB  - BACKGROUND: Various clinical reports suggest etanercept (ETN) has some efficacy
      in bone formation in rheumatoid arthritis (RA). To examine this effect, we
      investigated the gene expression of cytokines relevant to osteoblast/osteoclast
      differentiation, and evaluated histomorphometric findings in mature rats with
      collagen-induced arthritis (CIA). METHODS: Total RNA was extracted from knee
      joints with CIA after ETN or placebo administration. Subsequently, realtime-PCR
      was carried out to quantify the mRNAs encoding Wnt-1, Dickkopf-1 (DKK-1),
      receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegelin
      (OPG) and TNF (tumor necrosis factor)-alpha. In histomorphometric analysis, the
      infiltrating pannus volume and pannus surface, and the following items in contact
      with pannus surface were measured: osteoclast number, osteoid surface, osteoid
      volume and labeling surface. These were evaluated in the distal femur with CIA
      with or without ETN administration. RESULTS: TNF-alpha, RANKL and OPG mRNA
      expressions, linked to osteoclastogenesis, were not significantly different with
      or without ETN administration. ETN administration significantly increased Wnt-1
      mRNA expression, the osteoblast promoter, and decreased DKK-1 mRNA expression,
      the Wnt signal inhibitor. In histomorphometric analysis, pannus volume, pannus
      surface and osteoclast number, parameters of bone destruction, were not
      significantly different among groups. Osteoid volume, osteoid surface and
      labeling surface, parameters of bone formation, increased significantly with ETN
      administration. CONCLUSION: Our results suggest that ETN suppresses DDK-1
      expression, and, as a result, Wnt expression is promoted and osteoblastogenesis
      becomes more active, independent of the regulation of osteoclast activity. Marked
      bone formation is attributed to the fact that ETN directly promotes
      osteoblastogenesis, not as a result of suppressing osteoclastogenesis.

PMID- 24031148
TI  - Morphological and volumetric analysis of the development of atlantoaxial vertical
      subluxation in rheumatoid arthritis.
AB  - BACKGROUND: Cervical disorders in rheumatoid arthritis (RA) patients have been an
      important problem for a long time. Although the recent progression of the
      treatment strategies for RA might change the progression of atlantoaxial vertical
      subluxation (VS) in RA patients, to reveal the risk factors for VS progression
      should be important at present. Osteoporosis (OP) and RA share the same risk
      factors. The purposes of this study were to identify the progression of VS in RA,
      and to evaluate the relationship between the VS development and OP. METHODS:
      Eighty female patients with RA and 18 female patients with OP were
      retrospectively analyzed. The RA patients were divided into VS (10 patients) and
      non-VS groups (70 patients). Morphological parameters on coronal reconstructed
      computed tomography images were evaluated. Three-dimensional analysis was used to
      measure volumes and volumetric bone mineral densities (vBMDs) at the upper
      cervical spine (UCS). RESULTS: The VS group had higher age, longer RA symptom
      duration, and lower BMD at the lumbar spine compared to the non-VS group. Volumes
      and vBMDs at the UCS in RA group were greater than those in the OP group. In
      accordance with VS development, the lateral masses at the UCS became shorter, the
      C1 facet angle became sharper, and the volumes at the UCS decreased. However,
      there was no statistically significant relationship between vBMDs at the UCS and
      the VS development. CONCLUSION: The C1 facet angle became sharper with VS
      progression. Although 3-dimensional analysis revealed that decreases in the
      volumes at the UCS were associated with VS development, no significant
      relationship between OP and the VS development was observed.

PMID- 24031149
TI  - Lymphatic Vessel Density and Vascular Endothelial Growth Factor Expression in
      Squamous Cell Carcinomas of Lip and Oral Cavity: A Clinicopathological Analysis
      with Immunohistochemistry Using Antibodies to D2-40, VEGF-C and VEGF-D.
AB  - BACKGROUND: Squamous cell carcinoma (SCC) of the oral region often metastasizes
      to the cervical lymph nodes. To investigate whether the risk of cervical lymph
      node metastasis are predictable through lymphatic vessel density (LVD) and
      vascular endothelial growth factor (VEGF) expression, we assessed the
      relationship between LVD and clinicopathological parameters, and VEGF expression
      in SCC of the oral region. METHODS: The subjects were 109 patients with SCC of
      the oral region including the lip. Clinicopathological parameters examined for
      the association with LVD in a peritumoral hot spot were lymph node metastasis,
      histological grade and disease stage. The association with VEGF expression was
      similarly studied. LVD was detected by immunohistochemistry using D2-40. RESULTS:
      LVD was significantly higher in lip cancer than in other oral tumors (P <
      0.0001), while there were no significant differences of LVD among other cancers
      of the oral cavity. LVD tended to decrease with disease progression, increase of
      tumor size and increase of metastatic lymph node size. Eighty-four of 109 tumors
      were positive for VEGF-C or D. VEGF-C-positive tumor lesions were also positive
      for VEGF-D. Significantly higher levels of VEGF-C and D expressions were
      associated with large size of lymph node metastases (P = 0.02). CONCLUSION: SCC
      of the oral region including the lip that produces VEGF-C and D is significantly
      more likely to cause cervical lymph node metastasis. LVD in a peritumoral hot
      spot does not directly indicate the risk of cervical lymph node metastasis, but
      instead may reflect lymphangiogenesis due to VEGF together with loss of lymphatic
      vessels through tumor growth and progression.

PMID- 24031150
TI  - Long-term effects of livestock loss caused by dust storm on mongolian
      inhabitants: a survey 1 year after the dust storm.
AB  - BACKGROUND: Every spring, windblown dust storms damage human health and cause
      many domestic animal deaths in Mongolia. In particular, mass livestock death
      results in severe, direct economic loss to inhabitants. However, there is little
      empirical evidence to demonstrate the long-term effects of dust storm, especially
      in terms of health-related quality of life (HRQoL) secondary to livestock loss.
      We evaluated the long-term effects of livestock loss on Mongolian inhabitants.
      METHODS: We performed a cross-sectional survey of HRQoL using 36-item short-form
      health survey (SF-36, an index of the health condition) 1 year after a dust
      storm. The study subjects were 64 inhabitants of stricken areas of Mongolia. The
      data collection method was a face-to-face interview with a questionnaire.
      RESULTS: A total of 64 subjects were interviewed, 81% in the victims group and
      19% in the non-victims group. The mean number of livestock victims was 83.3, s =
      128.3. The SF-36 subscale scores were lower among people who lost livestock than
      among those who did not. Multiple regression analysis displayed a significant
      association between livestock loss and HRQoL (general health: = -0.476, P =
      0.021; vitality: = -0.359, P = 0.013). CONCLUSION: Our results provide
      preliminary evidence that livestock loss has long-term effects on HRQoL. Thus, it
      is necessary to conduct epidemiologic surveys on disorders associated with dust
      storms and devise countermeasures for the future.

PMID- 24031152
TI  - Effect of chemotherapy for luminal a breast cancer.
AB  - BACKGROUND: The addition of chemotherapy to endocrine therapy for luminal A
      breast cancer generally provides little benefit. However, the least benefit of
      chemotherapy in all patients with luminal A breast cancer is controversial.
      METHODS: This was a retrospective study of 140 patients with luminal A breast
      cancer who underwent surgery at Tottori University Hospital between 2001 and
      2010. Luminal A breast cancer was defined as positive for estrogen receptors
      and/or progesterone receptors and negative for human epidermal growth factor 2.
      Postoperative endocrine therapy was given to all patients. The prognostic values
      of age, tumor size, presence of lymphovascular invasion and lymph node status
      were evaluated. In addition, the prognostic value of chemotherapy for patients
      with identified risk factors affecting relapse-free survival and overall survival
      was evaluated. RESULTS: Tumor size greater than 2 cm and positive lymph node
      status were factors significantly affecting relapse-free survival. There were no
      factors significantly affecting overall survival. There was no significant
      difference in the relapse-free survival of patients with tumor size greater than
      2 cm and/or positive lymph node status who either received chemotherapy or not.
      However, the relapse event was earlier in patients with tumor size greater than 2
      cm and positive lymph node status who did not receive chemotherapy than in those
      who received chemotherapy. CONCLUSION: Chemotherapy could provide little benefit
      to patients with luminal A breast cancer. However, chemotherapy may bring them
      longer relapse-free periods.

PMID- 24031151
TI  - New strategy for overcoming resistance to chemotherapy of ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is one of the most sensitive solid tumors, with
      objective responses ranging from 60 to 80% even in patients with advanced stage.
      However, most patients ultimately recur and develop resistance to chemotherapy.
      As a result, the survival rate for patients with ovarian cancer has not improved
      over the past 20 years. Resistance to chemotherapy presents a major obstacle to
      attempt to improve the prognosis of patients with ovarian cancer. A new strategy
      is necessary to improve the prognosis of patients with ovarian cancer. METHODS:
      The mechanism of chemoresistance was reviewed to get over the resistance.
      Additionally, the biological characteristics of ovarian cancer and molecular
      targeted agents including signal-transduction inhibitors and anti-angiogenesis
      were discussed. RESULTS: Genetic diagnosis for chemosensitivity with drug
      resistance genes may be a useful predictor. Unfortunately, molecular-targeted
      therapy alone has been insufficient to improve the prognosis for patients with
      advanced ovarian cancer. Molecular molecular-targeted therapy should be carried
      out together with conventional cytotoxic agents. On the occasion of the use of
      the molecular targeted-agents, care of the appearance of the unexpected adverse
      effect should be important. CONCLUSION: The future research in this field will
      enable to develop an effective strategy for conquest of chemoresistance in
      ovarian cancer.

PMID- 24031153
TI  - Skin metastasis of hypopharyngeal carcinoma to the nasal tip.
AB  - Head and neck squamous cell carcinoma (SCC) rarely metastasizes to the skin.
      Metastases to the nasal tip from hypopharyngeal malignancies are extremely rare.
      We present a patient with nasal tip metastasis from hypopharyngeal SCC. A 74-year
      old man with hypopharyngeal and esophageal carcinomas had a red nodule on his
      nasal tip (so-called "clown nose"). Histopathologically, atypical squamoid cell
      nests had proliferated in a lobular fashion from the dermis to subcutaneous
      tissue. Those atypical cells were identical to primary tumor cells in the
      hypopharynx. Based on these findings, a diagnosis of skin metastasis from
      hypopharyngeal SCC was made. In patients with malignant disease, biopsy should be
      performed for any suspicious skin lesion. In a patient like ours, "clown nose"
      might be a symptom of cutaneous metastasis. When clinicians note a "clown nose",
      they should consider malignancies in the neck and chest areas. 

PMID- 24031154
TI  - Bilateral nevus comedonicus syndrome.
AB  - Nevus comedonicus is an uncommon skin abnormality characterized by an aggregation
      of dilated follicular orifices filled with keratinous material. Nevus comedonicus
      is occasionally complicated with other conditions including cataracts, skeletal
      defects, central nervous system abnormalities or other extra-cutaneous diseases
      (nevus comedonicus syndrome). Although most cases of nevus comedonicus occur
      unilaterally on the face, neck and chest, the lesions occasionally show a
      bilateral distribution (bilateral nevus comedonicus). We report here an unusual
      case of bilaterally disseminated nevus comedonicus with various systemic
      complications. A 62-year-old Japanese man presented with a 50-year history of
      numerous keratotic papules and comedo-like lesions, which gradually worsened with
      time. Physical examination revealed that the papules were skin-colored and 1-4 mm
      in diameter. Some papules had dark-black keratinous materials on their surface,
      giving them a comedo-like appearance. The lesions were located predominantly on
      the face, head, neck and trunk with symmetric distribution, following Blaschko's
      lines. The patient's past medical history was noteworthy; he had undergone
      surgical treatments for thyroid cancer, pneumothorax and schwannoma in the cauda
      equina. He also suffered from scoliosis, cervical spondylosis and atrial
      fibrillation. Histopathologic examination revealed dilated and invaginated
      follicular structures filled with lamellar keratin, compatible with nevus
      comedonicus. Our patient's case did not fit with any previously reported
      diseases, and we thought a diagnosis of "bilateral nevus comedonicus syndrome"
      was the most appropriate for our patient's condition. He was treated with topical
      retinoic acid and activated vitamin D3 ointment for 3 months each, but the
      lesions remained unchanged. 

PMID- 24031155
TI  - Limiting Distributions for Multitype Branching Processes.
AB  - In this paper the asymptotic behavior of multitype Markov branching processes
      with discrete or continuous time is investigated in the positive regular and
      nonsingular case when both the initial number of ancestors and the time tend to
      infinity. Some limiting distributions are obtained as well as multivariate
      asymptotic normality is proved. The paper considers also the relative frequencies
      of distinct types of individuals which is motivated by applications in the field
      of cell biology. We obtained non-random limits for the frequencies and
      multivariate asymptotic normality when the initial number of ancestors is large
      and the time of observation increases to infinity. In fact this paper continues
      the investigations of Yakovlev and Yanev [32] where the time was fixed. The new
      obtained limiting results are of special interest for cell kinetics studies where
      the relative frequencies but not the absolute cell counts are accessible to
      measurement.

PMID- 24031156
TI  - Reliability and Validity of Prisoner Self-Reports Gathered Using the Life Event
      Calendar Method.
AB  - Data collection using the life event calendar method is growing, but reliability
      is not well established. We examine test-retest reliability of monthly self
      reports of criminal behavior collected using a life event calendar from a random
      sample of minimum and medium security prisoners. Tabular analysis indicates
      substantial agreement between self-reports of drug dealing, property, and violent
      crime during a baseline interview (test) and a follow-up (retest) approximately
      three weeks later. Hierarchical analysis reveals that criminal activity reported
      during the initial test is strongly associated with responses given in the
      retest, and that the relationship varies only by the lag in days between the
      initial interview and the retest. Analysis of validity reveals that self-reported
      incarceration history is strongly predictive of official incarceration history
      although we were unable to address whether subjects could correctly identify the
      months they were incarcerated. African Americans and older subjects provide more
      valid responses but in practical terms the differences in validity are not large.

PMID- 24031157
TI  - Conducting Internet Research With the Transgender Population: Reaching Broad
      Samples and Collecting Valid Data.
AB  - Health research on transgender people has been hampered by the challenges
      inherent in studying a hard-to-reach, relatively small, and geographically
      dispersed population. The Internet has the potential to facilitate access to
      transgender samples large enough to permit examination of the diversity and
      syndemic health disparities found among this population. In this article, we
      describe the experiences of a team of investigators using the Internet to study
      HIV risk behaviors of transgender people in the United States. We developed an
      online instrument, recruited participants exclusively via websites frequented by
      members of the target population, and collected data using online quantitative
      survey and qualitative synchronous and asynchronous interview methods. Our
      experiences indicate that the Internet environment presents the investigator with
      some unique challenges and that commonly expressed criticisms about Internet
      research (e.g., lack of generalizable samples, invalid study participants, and
      multiple participation by the same subject) can be overcome with careful method
      design, usability testing, and pilot testing. The importance of both usability
      and pilot testing are described with respect to participant engagement and
      retention and the quality of data obtained online.

PMID- 24031159
TI  - Multifactorial Understanding of Ion Abundance in Tandem Mass Spectrometry
      Experiments.
AB  - In a bottom-up shotgun approach, the proteins of a mixture are enzymatically
      digested, separated, and analyzed via tandem mass spectrometry. The mass spectra
      relating fragment ion intensities (abundance) to the mass-to-charge are used to
      deduce the amino acid sequence and identify the peptides and proteins. The
      variables that influence intensity were characterized using a multi-factorial
      mixed-effects model, a ten-fold cross-validation, and stepwise feature selection
      on 6,352,528 fragment ions from 61,543 peptide ions. Intensity was higher in
      fragment ions that did not have neutral mass loss relative to any mass loss or
      that had a +1 charge state. Peptide ions classified for proton mobility as non
      mobile had lowest intensity of all mobility levels. Higher basic residue
      (arginine, lysine or histidine) counts in the peptide ion and low counts in the
      fragment ion were associated with lower fragment ion intensities. Higher counts
      of proline in peptide and fragment ions were associated with lower intensities.
      These results are consistent with the mobile proton theory. Opposite trends
      between peptide and fragment ion counts and intensity may be due to the different
      impact of factor under consideration at different stages of the MS/MS experiment
      or to the different distribution of observations across peptide and fragment ion
      levels. Presence of basic residues at all three positions next to the
      fragmentation site was associated with lower fragment ion intensity. The presence
      of proline proximal to the fragmentation site enhanced fragmentation and had the
      opposite trend when located distant from the site. A positive association between
      fragment ion intensity and presence of sulfur residues (cysteine and methionine)
      on the vicinity of the fragmentation site was identified. These results highlight
      the multi-factorial nature of fragment ion intensity and could improve the
      algorithms for peptide identification and the simulation in tandem mass
      spectrometry experiments.

PMID- 24031158
TI  - Relations of Parent-Youth Interactive Exchanges to Adolescent Socioemotional
      Development.
AB  - This study examined the relations of parent-youth agreement and disagreement
      during a joint problem-solving task and multi-methodological indices of
      socioemotional outcomes in adolescents (Mean age = 13). One hundred and sixty
      seven parents and their adolescent children participated. Each parent-youth pair
      played the interactive game Jenga, and their interactions were analyzed for
      frequency of elaborations (agreement during three or more conversational turns)
      and negotiations (disagreement during three or more conversational turns).
      Elaborations during parent-youth interactions were related to less negative
      classroom behavior, better self-regulation, and more task persistence in youth.
      Findings are discussed in light of the importance of parent-youth interaction and
      youth autonomy in adolescent socioemotional development.

PMID- 24031160
TI  - Estimation of Soft Tissue Mechanical Parameters from Robotic Manipulation Data.
AB  - Robotic motion planning algorithms used for task automation in robotic surgical
      systems rely on availability of accurate models of target soft tissue's
      deformation. Relying on generic tissue parameters in constructing the tissue
      deformation models is problematic because, biological tissues are known to have
      very large (inter- and intra-subject) variability. A priori mechanical
      characterization (e.g., uniaxial bench test) of the target tissues before a
      surgical procedure is also not usually practical. In this paper, a method for
      estimating mechanical parameters of soft tissue from sensory data collected
      during robotic surgical manipulation is presented. The method uses force data
      collected from a multiaxial force sensor mounted on the robotic manipulator, and
      tissue deformation data collected from a stereo camera system. The tissue
      parameters are then estimated using an inverse finite element method. The effects
      of measurement and modeling uncertainties on the proposed method are analyzed in
      simulation. The results of experimental evaluation of the method are also
      presented.

PMID- 24031161
TI  - Comprehensive assessment and network analysis of the emerging genetic
      susceptibility landscape of prostate cancer.
AB  - BACKGROUND: Recent advances in high-throughput genotyping have made possible
      identification of genetic variants associated with increased risk of developing
      prostate cancer using genome-wide associations studies (GWAS). However, the
      broader context in which the identified genetic variants operate is poorly
      understood. Here we present a comprehensive assessment, network, and pathway
      analysis of the emerging genetic susceptibility landscape of prostate cancer.
      METHODS: We created a comprehensive catalog of genetic variants and associated
      genes by mining published reports and accompanying websites hosting supplementary
      data on GWAS. We then performed network and pathway analysis using single
      nucleotide polymorphism (SNP)-containing genes to identify gene regulatory
      networks and pathways enriched for genetic variants. RESULTS: We identified
      multiple gene networks and pathways enriched for genetic variants including IGF
      1, androgen biosynthesis and androgen signaling pathways, and the molecular
      mechanisms of cancer. The results provide putative functional bridges between
      GWAS findings and gene regulatory networks and biological pathways.

PMID- 24031162
TI  - Safety and efficacy of sitagliptin-metformin in fixed combination for the
      treatment of type 2 diabetes mellitus.
AB  - The biguanide, metformin, is considered first-line treatment for type 2 diabetes.
      Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor acts through the incretin
      pathway and has a glucose dependent mode of action. The complementary
      hypoglycemic properties of these drugs make fixed dose combination treatment an
      attractive prospect. Evidence from recent clinical trials suggests a beneficial
      effect of the combination on efficacy, demonstrated by significant improvement of
      hemoglobin A1c (HbA1c), fasting and postprandial glucose levels. The fixed dose
      combination is likely to have greater patient tolerability compared with
      monotherapy with either agent because of low rates of hypoglycemia, weight
      neutrality, and lower rates of side effects. High acquisition cost and paucity of
      long-term safety data are, however, potential barriers to their wider use. An
      overview of the pharmacology and clinical outcomes from recent trials of the
      metformin-sitagliptin combination and how the combination could fit into the type
      2 diabetes treatment algorithm is presented in this review. 

PMID- 24031163
TI  - Decreased mRNA and Protein Expression of BDNF, NGF, and their Receptors in the
      Hippocampus from Suicide: An Analysis in Human Postmortem Brain.
AB  - Despite the devastating effect of suicide on numerous lives, there is still a
      lack of knowledge concerning its neurochemical aspects. There is increasing
      evidence that brain-derived neurotrophic factor (BDNF) and nerve growth factor
      (NGF) are involved in the pathophysiology and treatment of depression through
      binding and activating their cognate receptors TrkB and TrkA respectively. The
      present study was performed to examine whether the expression profiles of BDNF
      and/or TrkB as well as NGF and/or TrkA were altered in the hippocampus of
      postmortem brain of the participants, who had committed suicide and whether these
      alterations were associated with specific psychopathologic conditions. These
      studies were performed on the hippocampus of 21 suicide victims and 19 non
      psychiatric control individuals. The protein and mRNA levels of BDNF, TrkB, NGF,
      and TrkA were determined by sandwich enzyme-linked immunosorbent assay, Western
      blot and reverse transcription-PCR. Given the importance of BDNF and NGF and
      their cognate receptors in mediating physiological functions, including cell
      survival and synaptic plasticity, our findings of reduced expression of BDNF,
      TrkB, NGF, and TrkA on both the protein and mRNA levels of postmortem brains of
      suicide victims suggest that these molecules may play an important role in the
      pathophysiological aspects of suicidal behavior. 

PMID- 24031165
TI  - Employment and Household Tasks of Japanese Couples, 1994-2009.
AB  - The paper examines changes in the relationship between employment and household
      tasks of Japanese couples, using data drawn from national cross-sectional surveys
      in 1994, 2000 and 2009 of persons aged 20-49 and from the 2009 follow-up of the
      2000 survey. Wives' employment is structured by their husbands' employment time
      and earning power, as well as by their family situations including the presence
      and age of children and coresidence with parents. Housework hours of husbands,
      though very low, increased over time, while wives' hours decreased. Wives
      housework time decreases as their employment time increases. Marriage
      dramatically increases women's housework time but produces little change in men's
      time. Husbands' housework hours are positively correlated with reported marital
      satisfaction of both spouses.

PMID- 24031164
TI  - Model cell membranes: Techniques to form complex biomimetic supported lipid
      bilayers via vesicle fusion.
AB  - Vesicle fusion has long provided an easy and reliable method to form supported
      lipid bilayers (SLBs) from simple, zwitterionic vesicles on siliceous substrates.
      However, for complex compositions, such as vesicles with high cholesterol content
      and multiple lipid types, the energy barrier for the vesicle-to-bilayer
      transition is increased or the required vesicle-vesicle and vesicle-substrate
      interactions are insufficient for vesicle fusion. Thus, for vesicle compositions
      that more accurately mimic native membranes, vesicle fusion often fails to form
      SLBs. In this paper, we review three approaches to overcome these barriers to
      form complex, biomimetic SLBs via vesicle fusion: (i) optimization of
      experimental conditions (e.g., temperature, buffer ionic strength, osmotic
      stress, cation valency, and buffer pH), (ii) alpha-helical (AH) peptide-induced
      vesicle fusion, and (iii) bilayer edge-induced vesicle fusion. AH peptide-induced
      vesicle fusion can form complex SLBs on multiple substrate types without the use
      of additional equipment. Bilayer edge-induced vesicle fusion uses microfluidics
      to form SLBs from vesicles with complex composition, including vesicles derived
      from native cell membranes. Collectively, this review introduces vesicle fusion
      techniques that can be generalized for many biomimetic vesicle compositions and
      many substrate types, and thus will aid efforts to reliably create complex SLB
      platforms on a range of substrates.

PMID- 24031166
TI  - Bovine papillomavirus type 4 L1 gene transfection in a Drosophila S2 cell
      expression system: absence of L1 protein expression.
AB  - The development of a bovine papillomavirus (BPV) vaccine is an outstanding
      challenge. BPV protein L1 gene transfection in the Drosophila melanogaster S2
      cell expression system failed to produce L1 protein notwithstanding correct L1
      gene insertion. Severe genetic inbalance in the host cell line, including
      cytogenetic alterations, may account for the lack of protein expression. 

PMID- 24031167
TI  - Survival and replication of Escherichia coli O157:H7 inside the mice peritoneal
      macrophages.
AB  - The replication of Escherichia coli O157:H7 on the resident peritoneal
      macrophages of four mice strains (BALB/c, CD1, C57BL, and Swiss) has been
      investigated. Macrophagial bactericidal killing activity was estimated via
      studying their ability to internalize (gentamicin-protected) E. coli during 2, 4,
      24, and 48 h assays. Host genetic background has been found to show no
      significant effect on the ability of resident peritoneal macrophages to kill E.
      coli O157:H7. 

PMID- 24031168
TI  - The relation between Escherichia coli surface functional groups' composition and
      their physicochemical properties.
AB  - Escherichia coli surface characteristics including hydrophobicity,
      electrophoretic mobility and surface functional groups' composition were
      investigated. These characteristics were determined respectively by water contact
      angle measurements, microelectrophoresis and x-ray photoelectron spectroscopy
      (XPS). The relation between the physicochemical properties and functional groups'
      composition was also examined. The electrophoretic mobility at pH 7 appeared to
      be governed on the cell surface by the (O=C) functional groups. The cell
      surface's hydrophilicity was associated with high levels of (C-(O.N)) and (OH- (C
      O-C)) functional groups, whereas the cell surface's hydrophobicity was associated
      with (C-(C,H)) functional groups. 

PMID- 24031169
TI  - Comparative evaluation of the Nitrate Reductase Assay and the Resazurin
      Microtitre Assay for drug susceptibility testing of Mycobacterium tuberculosis
      against first line anti-tuberculosis drugs.
AB  - Tuberculosis remains as a serious infection disease of worldwide distribution,
      with high morbidity and mortality, mainly in low socio-economic condition
      countries. The state of emergency of tuberculosis caused by the resistant and
      multidrug-resistant (MDR) strains, became the main threat to the tuberculosis
      treatment and control programs. A fast detection method for the resistant strains
      will allow the implementation of an adequate treatment and contribute for
      controlling the dissemination of these resistant strains. This study evaluated
      the performance of the nitrate reductase assay in solid (NRA-LJ) and liquid (NRA
      7H9) media, to determine the susceptibility to first line anti-tuberculosis
      drugs: isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and streptomycin
      (SMR). Both methods NRA-LJ and NRA-7H9 were evaluated among 18 strains with a
      known susceptibility profile. The resazurin microtiter assay (REMA) was performed
      as a reference method. One hundred percent of accordance was observed between NRA
      7H9 and REMA for the four tested drugs. When the NRA-LJ method was compared to
      REMA, the sensitivity and the specificity to INH, RMP, EMB and SMR were 100%, 100
      %, 85.7%, 76.9% and 80%, 100%, 75% and 80%, respectively. From the 57 clinical
      isolates of M. tuberculosis evaluated by NRA-7H9 and REMA, 56 (98.2%) were
      sensitive to all antibiotics tested (INH, RMP, EMB and SMR) by the NRA-7H9
      method, while three of these strains were resistant to INH by REMA. One strain
      showed resistance to INH and RMP for both methods, and MIC of 1.0 MUg/ml to INH
      for both methods, while MIC of 1.0 and 2.0 MUg/ml to RMP for REMA and NRA-7H9,
      respectively. The three assays showed a high level of agreement for rapid
      detection of rifampicin and isoniazid resistance. Regarding rapidness, the
      detection of color change in the NRA method is within instants as compared to the
      overnight incubation required for the REMA test. NRA might represent an
      inexpensive and alternative assay for rapid detection of resistance in low-income
      countries. 

PMID- 24031170
TI  - Diagnosis of neonatal group B Streptococcus sepsis by nested-PCR of residual
      urine samples.
AB  - Group B streptococcus (GBS) remains the most common cause of early-onset sepsis
      in newborns. Laboratory gold-standard, broth culture methods are highly specific,
      but lack sensitivity. The aim of this study was to validate a nested-PCR and to
      determine whether residue volumes of urine samples obtained by non invasive, non
      sterile methods could be used to confirm neonatal GBS sepsis. The nested-PCR was
      performed with primers of the major GBS surface antigen. Unavailability of
      biological samples to perform life supporting exams, as well as others to
      elucidate the etiology of infections is a frequent problem concerning newborn
      patients. Nevertheless, we decided to include cases according to strict criteria:
      newborns had to present with signs and symptoms compatible with GBS infection; at
      least one of the following biological samples had to be sent for culture: blood,
      urine, or cerebrospinal fluid; availability of residue volumes of the samples
      sent for cultures, or of others collected on the day of hospitalization, prior to
      antibiotic therapy prescription, to be analyzed by PCR; favorable outcome after
      GBS empiric treatment. In only one newborn GBS infection was confirmed by
      cultures, while infection was only presumptive in the other three patients (they
      fulfilled inclusion criteria but were GBS-culture negative). From a total of 12
      biological samples (5 blood, 3 CSF and 4 urine specimen), eight were tested by
      culture methods (2/8 were positive), and 8 were tested by PCR (7/8 were
      positive), and only 4 samples were simultaneously tested by both methods (1
      positive by culture and 3 by PCR). In conclusion, although based on a restricted
      number of neonates and samples, our results suggest that the proposed nested-PCR
      might be used to diagnose GBS sepsis as it has successfully amplified the three
      types of biological samples analyzed (blood, urine and cerebrospinal fluid), and
      was more sensitive than culture methods as PCR in urine confirmed diagnosis in
      all four patients. Moreover, PCR has enabled us to use residue volumes of urine
      samples collected by non invasive, non sterile methods, what is technically
      adequate as GBS is not part of the normal urine flora, thus avoiding invasive
      procedures such as suprapubic bladder punction or transurethral catheterization.
      At the same time, the use of urine instead of blood samples could help preventing
      newborns blood spoliation. 

PMID- 24031171
TI  - Case report: disseminated dermatophytosis by microsporum gypseum in a systemic
      lupus erythematosus patient.
AB  - Mycosis is a major contributor to morbidity and mortality in patients with
      systemic lupus erythematosus and frequent exposition to an infectious source
      could enhance the development of dermatophytic infections. A case of disseminated
      dermatophytosis by Microsporum gypseum is reported in a systemic lupus
      erythematosus (SLE) patient. 

PMID- 24031173
TI  - Low prevalence of high risk human papillomavirus in normal oral mucosa by hybrid
      capture 2.
AB  - High risk human papillomavirus (HR-HPV) are recognized as a necessary factor to
      development cervical cancer. During the last decade many studies have found HR
      HPV in oral squamous cell carcinoma (OSCC) and normal oral mucosa, however the
      association between HR-HPV and OSCC is still uncertain. The aim of the study was
      to determine DNA HR-HPV in normal oral cavity of healthy adults. A cross
      sectional study was performed; samples from 77 patients with normal oral cavity
      were collected at the Dentistry school, Autonomous University of Yucatan, Merida,
      Yucatan, Mexico. HR-HPV was detected by hybrid capture 2. One sample out of
      77(1.2%) was positive for HR-PVH. It was from a man of 50 years old. HRHPV is
      present in low rate among healthy oral mucosa. Hybrid capture 2 could be a good
      methodology for large epidemiology studies. 

PMID- 24031172
TI  - Echovirus 6 associated to aseptic meningitis outbreak, in Sao Joaquim da Barra,
      Sao Paulo, Brazil.
AB  - An aseptic meningitis outbreak occurred during a period from February to May 2004
      in Sao Joaquim da Barra, a town in the northern region of Sao Paulo State. A
      total of 40 cases were reported to the Epidemiological Surveillance Center of Sao
      Paulo State. Cerebrospinal fluid samples obtained from 23 patients were sent to
      the Adolfo Lutz Institute for isolation of the virus. These samples were
      inoculated into RD, HEp2 and Vero cell lineages and those presenting a
      cytopathogenic effect were selected for analysis by indirect immunofluorescence
      assay (IFA), neutralization testing (Nt) and reverse transcriptase-polymerase
      chain reaction (RT-PCR). Cytopathogenic effects were observed in 52.2% (12/23) of
      these samples. All isolated viruses were identified as human enterovirus by IFA
      and RT-PCR and echovirus 6 was typed by IFA and Nt. Our results confirmed the
      participation and importance of echovirus as the etiological agent responsible
      for this outbreak and the serotype diversity of human enteroviruses circulating
      in Sao Paulo State. 

PMID- 24031174
TI  - Catalase activity of different Candida species after exposition to specific
      antiserum.
AB  - Antisera were developed in rabbits after challenge with intracellular antigens of
      Candida albicans, C. tropicalis and C. parapsilosis. Microorganism catalase has
      been correlated with virulence, resistance to drugs and immunogenicity. The
      intracellular catalase is consistently present in strains of Candida and in this
      paper, the enzyme activity was analysed by PAGE after exposition to antisera. The
      catalases of C. albicans, C. parapsilosis and C. tropicalis were immunogenic and
      differed in their binding to specific antibodies raised in rabbits. Tests of
      cross-reactivity between different Candida species showed that when antiserum
      from C. albicans immunized rabbit was incubated with intracellular extracts of
      these three Candida species, the catalases activities were abolished. However,
      the antisera from C. parapsilosis or C. tropicalis immunized rabbits did not
      affect the catalase activity of C. albicans; the enzyme of C. albicans was
      inactivated only by the antiserum to the catalase of own C. albicans. The
      antiserum to the catalase of C. tropicalis was species-specific and did not cross
      react with catalases of C. albicans and C. parapsilosis. The activities of
      Aspergillus niger and bovine catalases were not affected by the antiserum from
      any Candida immunized rabbits. This report is a preliminary study of specific
      antisera that react against intracellular catalase of Candida sp. and neutralize
      the enzymatic activity. Further study is necessary to develop species-specific
      antibody once differences in the susceptibility of the Candida species to
      commonly used antifungal drugs make identification to the species level
      important. 

PMID- 24031175
TI  - Synergistic action of starch and honey against Candida albicans in correlation
      with diastase number.
AB  - To evaluate the synergistic action of starch on the antifungal activity of honey,
      a comparative method of adding honey with and without starch to culture media was
      used. Candida albicans has been used to determine the minimum inhibitory
      concentration (MIC) of five varieties of honey. In a second step, lower
      concentrations of honey than the MIC were incubated with a set of concentrations
      of starch added to media to determine the minimum synergistic inhibitory
      concentration (MSIC). The MIC for the five varieties of honey without starch
      against C. albicans ranged between 40% and 45% (v/v). When starch was incubated
      with honey and then added to media, a MIC drop has been noticed with each
      variety. It ranged between 7% and 25%. A negative correlation has been
      established between the MIC drop and the diastase number (DN). 

PMID- 24031176
TI  - Cytotoxic T cell adjuvant effects of three Salmonella enterica flagellins.
AB  - Bacterial flagellins are important virulence-associated factors and strong
      inducers of inflammatory responses in mammalian hosts. Flagellins have also been
      investigated as potential vaccine adjuvants, either for induction of humoral or
      cellular immune responses, to different target antigens. In this study we
      investigated the adjuvant properties of three Salmonella enterica flagellins
      types (FliCd, FliCi and FljB) to an ovalbumin-derived CD8(+) T cell-restricted
      epitope (OVA257-264). Although mice immunized with the three tested flagellins
      elicited antigen-specific activated CD8(+) T cells, only animals immunized with
      FliCi and FliCd flagellins admixed with ovalbumin mounted specific in vivo
      cytotoxic responses to peptide-pulsed target cells. The present results indicate
      that Salmonella flagellins are endowed with type-specific adjuvant effects toward
      murine CD8(+) T cells, a feature that may impact their use as adjuvants for
      prophylatic or therapeutic vaccines. 

PMID- 24031177
TI  - Effect of the trehalose levels on the screening of yeast as probiotic by in vivo
      and in vitro assays.
AB  - Probiotics are viable defined microorganisms (bacteria or yeasts) that exert a
      beneficial effect on the health of the host when ingested in adequate amounts.
      Screening for such biotherapeutic agents is commonly performed by in vitro assays
      simulating gastrointestinal environment to determine the ability to survive in
      the digestive tract. In the present study, the possibility of extrapolation of
      data obtained in in vitro assays to in vivo conditions was studied using five
      Saccharomyces cerevisiae strains isolated from Brazilian Atlantic rain forest.
      Trehalose contents and survival after exposure to a combination of physiological
      stresses generally found in the gastrointestinal tract of humans were determined
      for the five yeasts and compared to the behavior of Saccharomyces boulardii, a
      well-known probiotic. The results were completed with the colonization capacity
      of the gastrointestinal tract of gnotobiotic mice by these yeast strains. Some
      results obtained by in vitro assays are not confirmed by in vivo experiments,
      indicating that the extrapolation cannot be always done. 

PMID- 24031178
TI  - Occurrence of campylobacter species in healthy well-nourished and malnourished
      children.
AB  - The occurrence of Campylobacter species in healthy, well-nourished and healthy,
      malnourished children of low socioeconomic level in Southern Chile was
      determined. Campylobacter carriers were significantly most frequent among
      malnourished (31.4%) than among well-nourished (9.9%) children. Six species were
      isolated from malnourished children whereas four were found among well-nourished
      children. C. upsaliensis was the most frequent (13.3%) species isolated from
      malnourished children, followed by C. lari (7.6%) and C. fetus ssp. fetus (1.9%).

PMID- 24031179
TI  - Invasive Trichosporon cutaneum infection in an infant with wilms' tumor.
AB  - Fungal infections are increasingly being reported in immuno-compromised patients.
      In this study we report a case of systemic Trichosporon cutaneum infection in an
      infant with Wilms' tumor. This is the first time that an invasive infection for
      T. cutaneum has been reported in a Wilms' tumor patient. 

PMID- 24031180
TI  - Antifungal activity of the essential oil from Calendula officinalis L.
      (asteraceae) growing in Brazil.
AB  - This study tested in vitro activity of the essential oil from flowers of
      Calendula officinalis using disk-diffusion techniques. The antifungal assay
      results showed for the first time that the essential oil has good potential
      antifungal activity: it was effective against all 23 clinical fungi strains
      tested. 

PMID- 24031181
TI  - Leaf-cutting ant faecal fluid and mandibular gland secretion: effects on
      microfungi spore germination.
AB  - The mandibular gland secretion (MGS) and the faecal fluid (FF) of the leaf
      cutting ant Atta sexdens rubropilosa Forel affected the spore germination of
      selected microfungi isolated from nests of this insect. MGS was more effective
      than the FF, completely inhibiting the spore germination of four out of six
      microfungi species. 

PMID- 24031182
TI  - Genetic and metabolic diversity of pink-pigmented facultative methylotrophs in
      phyllosphere of tropical plants.
AB  - Diversity of Pink-Pigmented Facultative Methylotrophs (PPFMs) in phyllosphere of
      cotton, maize and sunflower was determined based on differential carbon-substrate
      utilization profile and Random Amplified Polymorphic DNA data. Results indicate
      that six diversified groups of PPFMs are found in these crops. Sunflower and
      maize phyllosphere harbor four different groups of methylobacteria while cotton
      has only two groups. 

PMID- 24031183
TI  - Inoculum padronization for the production of cutinase by Fusarium oxysporum.
AB  - Cutinase is a versatile enzyme showing several interesting properties for
      application in industrial processes. The widespread use of this enzyme depends on
      the development of an efficient and low-cost production system. One of the most
      important steps in a fermentation process is the standardization of the inoculum
      characteristics. In this study, the production of cutinase by Fusarium oxysporum
      showed a statistically significant relationship with both the inoculum size and
      the inoculum PDA pH. The greatest activities were 19.1 U/mL at PDA pH 7.0 and
      22.72 U/mL using an aliquot of 12.72 * 10(7) spores/mL. The macroscopic
      characteristics of the colonies of Fusarium oxysporum changed according to the
      variation of the medium pH, with the best results recorded in those colonies
      presenting a cotton white aspect. 

PMID- 24031184
TI  - Lignolytic enzymes produced by Trametes villosa ccb176 under different culture
      conditions.
AB  - The expression of the enzymatic system produced by basidiomycetous fungi, which
      is involved in the degradation of xenobiotics, mainly depends on culture
      conditions, especially of the culture medium composition. Trametes villosa is a
      strain with a proven biotechnological potential for the degradation of
      organochlorine compounds and for the decolorization of textile dyes. The
      influence of glucose concentration, addition of a vegetable oil-surfactant
      emulsion, nature of the surfactant and the presence of manganese and copper on
      the growth, pH and production of laccase, total peroxidase and manganese
      dependent peroxidase activities were evaluated. In general, acidification of the
      medium was observed, with the pH reaching a value close to 3.5 within the first
      days of growth. Laccase was the main activity detected under the different
      conditions and was produced throughout the culture period of the fungus,
      irrespective of the growth phase. Supplementation of the medium with vegetable
      oil emulsified with a surfactant induced manganese-dependent peroxidase activity
      in T. villosa. Higher specific yields of laccase activity were obtained with the
      addition of copper. 

PMID- 24031185
TI  - Biological control of Penicillium italicum, P. digitatum and P. expansum by the
      predacious yeast Saccharomycopsis schoenii on oranges.
AB  - In this study we evaluated the ability of Saccharomycopsis schoenii Nadson and
      Krassiln (UWO-PS 80-91) as biocontrol agent against plant pathogenic filamentous
      fungi P. expansum Link (UFMG 01-2002), P. italicum Wehmer (LCP 61.1199), and P.
      digitatum (Pers.: Fr.) (LCP 984263, LCP 68175 and LCP 4354). S. schoenii was able
      to reduce disease severity in oranges inoculated with all fungi. Among the
      phytopathogens, P. digitatum LCP4354 was the most virulent whereas P. digitatum
      LCP 68175 was the most susceptible to predation. The yeast was able to survive
      for 21 days on the fruit surface and did not produce lesions on oranges.
      Production of antagonistic substances by S. schoenii was not detected using
      standard techniques. Our results point to the potential use of S. schoenii to
      control postharvest phytopathogens in fruits. 

PMID- 24031186
TI  - Effect of cinnamomum zeylanicum blume essential oil on the growth and
      morphogenesis of some potentially pathogenic Aspergillus species.
AB  - Cinnamomum zeylanicum Blume is known for a wide range of medicinal properties.
      This study aimed to assess the interference of C. zeylanicum essential oil on the
      growth and morphogenesis of some potentially pathogenic Aspergillus species. The
      essential oil presented strong antifungal effect causing the growth inhibition of
      the assayed strains and development of large growth inhibition zones. MIC50 and
      MIC90 values were 40 and 80 MUL/mL, respectively. 80, 40 and 20 MUL/mL of the oil
      strongly inhibited the radial mycelial growth of A. niger, A. flavus and A.
      fumigatus along 14 days. 80 and 40 MUL/mL of the oil caused a 100% inhibition of
      the fungal spore germination. Main morphological changes observed under light
      microscopy provided by the essential oil in the fungal strains were decreased
      conidiation, leakage of cytoplasm, loss of pigmentation and disrupted cell
      structure indicating fungal wall degeneration. It is concluded that C. zeylanicum
      essential oil could be known as potential antifungal compound, particularly, to
      protect against the growth of Aspergillus species. 

PMID- 24031187
TI  - Cultivation of Arthrospira (spirulina) platensis in desalinator wastewater and
      salinated synthetic medium: protein content and amino-acid profile.
AB  - Arthrospira (Spirulina) platensis was cultivated in laboratory under controlled
      conditions (30 degrees C, photoperiod of 12 hours light/dark provided by
      fluorescent lamps at a light intensity of 140 MUmol photons.m(-2).s(-1) and
      constant bubbling air) in three different culture media: (1) Paoletti medium
      (control), (2) Paoletti supplemented with 1 g.L(-1) NaCl (salinated water) and
      (3) Paoletti medium prepared with desalinator wastewater. The effects of these
      treatments on growth, protein content and amino acid profile were measured.
      Maximum cell concentrations observed in Paoletti medium, Paoletti supplemented
      with salinated water or with desalinator wastewater were 2.587, 3.545 and 4.954
      g.L(-1), respectively. Biomass in medium 3 presented the highest protein content
      (56.17%), while biomass in medium 2 presented 48.59% protein. All essential amino
      acids, except lysine and tryptophan, were found in concentrations higher than
      those requiried by FAO. 

PMID- 24031188
TI  - Properties of an amylase from thermophilic Bacillus SP.
AB  - alpha-Amylase production by thermophilic Bacillus sp strain SMIA-2 cultivated in
      liquid cultures containing soluble starch as a carbon source and supplemented
      with 0.05% whey protein and 0.2% peptone reached a maximum activity at 32 h, with
      levels of 37 U/mL. Studies on the amylase characterization revealed that the
      optimum temperature of this enzyme was 90 degrees C. The enzyme was stable for 1
      h at temperatures ranging from 40-50 degrees C while at 90 degrees C, 66% of its
      maximum activity was lost. However, in the presence of 5 mM CaCl2, the enzyme was
      stable at 90 degrees C for 30 min and retained about 58% residual activity after
      1 h. The optimum pH of the enzyme was found to be 8.5. After incubation of enzyme
      for 2 h at pH 9.5 and 11.0 was observed a decrease of about 6.3% and 16.5% of its
      original activity. At pH 6.0 the enzyme lost about 36% of its original activity.
      The enzyme was strongly inhibited by Co(2+), Cu(2+) and Ba(2+), but less affected
      by Mg(2+), Na(+) and K(+). In the presence of 2.0 M NaCl, 63% of amylase activity
      was retained after 2 h incubation at 45 degrees C. The amylase exhibited more
      than 70% activity when incubated for 1 h at 50 degrees C with sodium dodecyl
      sulphate. However, very little residual activity was obtained with sodium
      hypochlorite and with hydrogen peroxide the enzyme was completely inhibited. The
      compatibility of Bacillus sp SMIA-2 amylase with certain commercial detergents
      was shown to be good as the enzyme retained 86%, 85% and 75% of its activity
      after 20 min incubation at 50 degrees C in the presence of the detergent brands
      Omo((r)), Campeiro((r)) and Tide((r)), respectively. 

PMID- 24031189
TI  - Production and characterization of glucoamylase from fungus Aspergillus awamori
      expressed in yeast Saccharomyces cerevisiae using different carbon sources.
AB  - Glucoamylase is widely used in the food industry to produce high glucose syrup,
      and also in fermentation processes for production beer and ethanol. In this work
      the productivity of the glucoamylase of Aspergillus awamori expressed by the
      yeast Saccharomyces cerevisiae, produced in submerged fermentation using
      different starches, was evaluated and characterized physico-chemically. The
      enzyme presented high specific activity, 13.8 U/mgprotein or 2.9 U/mgbiomass,
      after 48 h of fermentation using soluble starch as substrate. Glucoamylase
      presented optimum activity at temperature of 55 degrees C, and, in the substratum
      absence, the thermostability was for 1h at 50 degrees C. The optimum pH of
      activity was pH 3.5 - 4.0 and the pH stability between 5.0 and 7.0. The half life
      at 65 degrees C was at 30.2 min, and the thermal energy of denaturation was 234.3
      KJ mol(-1). The hydrolysis of different substrate showed the enzyme's preference
      for the substrate with a larger polymerization degree. The gelatinized corn
      starch was the substratum most susceptible to the enzymatic action. 

PMID- 24031190
TI  - Novel process for the simultaneous extraction and degumming of banana fibers
      under solid-state cultivation.
AB  - Various process parameters for the production of polygalacturonase by
      Streptomyces lydicus under solid-state fermentation were optimized. The optimum
      particle size of wheat bran for polygalacturonase production was in the range of
      500-1000 MUm. Initial moisture content of 70% was found to be the optimum for
      enzyme production. The most suitable inoculum size was 1.25 * 10(5) CFU/mL and
      the optimum incubation temperature was 30 degrees C. Addition of carbon sources
      resulted in 37% increase in enzyme yield (425 U/g), whereas no significant
      enhancement was obtained on nitrogen supplementation. Maximum enzyme yield was
      recorded at 72 h. When compared to the initial production medium (108.5 U/g), the
      enzyme yield was 3.9 fold after optimization. Solid-state fermentation was
      effectively employed to develop a novel process for the simultaneous extraction
      and degumming of banana fibers. Streptomyces lydicus was allowed to grow on wheat
      bran medium in which banana leaf sheath pieces were incorporated and the fiber
      bundles were separated after a two-step fermentative process. 

PMID- 24031191
TI  - Production of endoglucanase by the native strains of Streptomyces isolates in
      submerged fermentation.
AB  - Cellulase is a complex enzyme system, commercially produced by filamentous fungi
      under solid-state and submerged cultivation. It has wide applicability in
      textile, food and beverage industry for effective saccharification process. In
      this study, cellulolytic enzyme activity, particularly endoglucanase of 26
      Streptomyces strains isolated from garden soil was examined, including two
      isolates selected on the basis of potential cellulolytic activity on Bennett's
      agar medium. To enhance the endoglucanase formation in broth culture, different
      conditions including carbon and nitrogen sources, and growth conditions were
      tested. The maximum endoglucanase activity (11.25-11.90 U/mL) was achieved within
      72-88 h in fermentation medium containing Tween-80, followed by phosphate
      sources. Both cellulolytic Streptomyces isolates gave almost equal quantity of
      enzyme in all trials. However the effect of medium ingredients on endoglucanase
      induction diverged with strains in some extent. 

PMID- 24031192
TI  - Bioassay assessment of metarhizium anisopliae (metchnikoff) sorokin
      (deuteromycota: hyphomycetes) against Oncometopia facialis (signoret) (hemiptera:
      cicadellidae).
AB  - Citrus Variegated Chlorosis (CVC) is an economically important, destructive
      disease in Brazil and is caused by Xylella fastidiosa and transmitted by
      sharpshooter insects. In this study, the efficacy of the fungus Metarhizium
      anisopliae in controlling the sharpshooter Oncometopia facialis was studied by
      bioassay conditions. In the bioassay, insects were sprayed with a suspension
      containing 5 X 10(7) conidia mL(-1). Adults captured in the field were treated in
      groups of 10 in a total of 11 replications per treatment. Significant differences
      between the natural mortality and the mortality of insects treated with the
      fungus were observed 6 days after inoculations (P<0.05). These significant
      differences increased until 10 days after treatment. The fungus caused 87.1%
      mortality, with the LT50 varying from 5 to 6 days. The LC50 was 1.2 X 10(6)
      conidia mL(-1), varying from 7.7 X 10(5) to 2 X 10(6) conidia mL(-1). The results
      showed that the sharpshooter O. facialis was susceptible to the entomopathogenic
      action of M. anisopliae in controlled condition during bioassay. 

PMID- 24031193
TI  - Biodegradability of commercial and weathered diesel oils.
AB  - This work aimed to evaluate the capability of different microorganisms to degrade
      commercial diesel oil in comparison to a weathered diesel oil collected from the
      groundwater at a petrol station. Two microbiological methods were used for the
      biodegradability assessment: the technique based on the redox indicator 2,6 
      dichlorophenol indophenol (DCPIP) and soil respirometric experiments using
      biometer flasks. In the former we tested the bacterial cultures Staphylococcus
      hominis, Kocuria palustris, Pseudomonas aeruginosa LBI, Ochrobactrum anthropi and
      Bacillus cereus, a commercial inoculum, consortia obtained from soil and
      groundwater contaminated with hydrocarbons and a consortium from an
      uncontaminated area. In the respirometric experiments it was evaluated the
      capability of the native microorganisms present in the soil from a petrol station
      to biodegrade the diesel oils. The redox indicator experiments showed that only
      the consortia, even that from an uncontaminated area, were able to biodegrade the
      weathered diesel. In 48 days, the removal of the total petroleum hydrocarbons
      (TPH) in the respirometric experiments was approximately 2.5 times greater when
      the commercial diesel oil was used. This difference was caused by the consumption
      of labile hydrocarbons, present in greater quantities in the commercial diesel
      oil, as demonstrated by gas chromatographic analyses. Thus, results indicate that
      biodegradability studies that do not consider the weathering effect of the
      pollutants may over estimate biodegradation rates and when the bioaugmentation is
      necessary, the best strategy would be that one based on injection of consortia,
      because even cultures with recognised capability of biodegrading hydrocarbons may
      fail when applied isolated. 

PMID- 24031194
TI  - Biodiversity and phylogenetic analysis of culturable bacteria indigenous to
      Khewra salt mine of pakistan and their industrial importance.
AB  - Culturable bacterial biodiversity and industrial importance of the isolates
      indigenous to Khewra salt mine, Pakistan was assessed. PCR Amplification of 16S
      rDNA of isolates was carried out by using universal primers FD1 and rP1and
      products were sequenced commercially. These gene sequences were compared with
      other gene sequences in the GenBank databases to find the closely related
      sequences. The alignment of these sequences with sequences available from GenBank
      database was carried out to construct a phylogenetic tree for these bacteria.
      These genes were deposited to GenBank and accession numbers were obtained. Most
      of the isolates belonged to different species of genus Bacillus, sharing 92-99%
      16S rDNA identity with the respective type strain. Other isolates had close
      similarities with Escherichia coli, Staphylococcus arlettae and Staphylococcus
      gallinarum with 97%, 98% and 99% 16S rDNA similarity respectively. The abilities
      of isolates to produce industrial enzymes (amylase, carboxymethylcellulase,
      xylanase, cellulase and protease) were checked. All isolates were tested against
      starch, carboxymethylcellulose (CMC), xylane, cellulose, and casein degradation
      in plate assays. BPT-5, 11,18,19 and 25 indicated the production of copious
      amounts of carbohydrates and protein degrading enzymes. Based on this study it
      can be concluded that Khewra salt mine is populated with diverse bacterial
      groups, which are potential source of industrial enzymes for commercial
      applications. 

PMID- 24031195
TI  - Solubilization of insoluble inorganic phosphate by Burkholderia cepacia DA23
      isolated from cultivated soil.
AB  - A mineral phosphate solubilizing bacterium, Burkholderia cepacia DA23 has been
      isolated from cultivated soils. Phosphate-solubilizing activities of the strain
      against three types of insoluble phosphate were quantitatively determined. When
      3% of glucose concentration was used for carbon source, the strain had a marked
      mineral phosphate-solubilizing activity. Mineral phosphate solubilization was
      directly related to the pH drop by the strain. Analysis of the culture medium by
      high pressure liquid chromatography identified gluconic acid as the main organic
      acid released by Burkholderia cepacia DA23. Gluconic acid production was
      apparently the result of the glucose dehydrogenase activity and glucose
      dehydrogenase was affected by phosphate regulation. 

PMID- 24031196
TI  - Natural occurrence of nivalenol and mycotoxigenic potential of Fusarium
      graminearum strains in wheat affected by head blight in Argentina.
AB  - The principal agents of Fusarium head blight in the main cropping area of
      Argentina were investigated in heavily infected samples. The ability of the
      isolates to produce trichothecenes was determined by GC and HPLC. Fusarium
      graminearum was the predominant species and of 33 isolates, 10 produced
      deoxinivalenol (DON) (0.1- 29 mg kg(-1)), 13 produced both deoxinivalenol (1.0-
      708 mg kg(-1)) and nivalenol (0.1- 6.2mg kg(-1)), 12 produced 3
      acetyldeoxinivalenol (0.1- 14 mg kg(-1)), 13 produced 15-acetyldeoxinivalenol
      (0.1- 1.9 mg kg(-1)), 10 produced Fusarenone X (0.1- 2.4 mg kg(-1)) and 7
      produced zearalenone (0.1- 0.6 mg kg(-1)). These results suggest that F.
      graminearum strains isolated from the wheat growing regions in Argentina belong
      to DON chemotype. Although some strains produced both deoxinivalenol and
      nivalenol, nivalenol was produced in lower levels. The natural occurrence of
      nivalenol in wheat affected by head-blight collected in the main production area
      during two years (2001-2002) was also determined. From 19 samples 13 were
      contaminated with deoxinivalenol in a range of 0.3 to 70 mg kg(-1)and 2 samples
      with both deoxinivalenol (7.5 and 6.7 mg kg(-1)) and nivalenol (0.05 and 0.1 mg
      kg(-1)), respectively. This is the first report of natural occurrence of
      nivalenol in wheat cultivate in Argentina. 

PMID- 24031197
TI  - Antimicrobial activity and potential use of monoterpenes as tropical fruits
      preservatives.
AB  - Banana, papaya and pineapple are the most consumed tropical fruits in the world,
      being Brazil one of the main producers. Fungi Colletotrichum musae,
      Colletotrichum gloeosporioides and Fusarium subglutinans f.sp. ananas cause
      severe post harvest diseases and losses in fruits quality. The aim of this work
      was to evaluate the effectiveness of five monoterpenes to inhibit the mycelial
      growth and conidia germination of these three phytopathogens. The monoterpenes
      citral, citronellal, L-carvone, isopullegol and alpha-pinene were diluted in
      ethanol to final concentrations from 0.2 to 1%. All monoterpenes were found to
      inhibit the growth of the three studies fungi in a dose-dependent manner. Citral
      was the most effective of the oils tested and showed potent fungicidal activity
      at concentrations above 0.5%. Also, in vivo evaluation with these tropical fruits
      demonstrated the efficiency of citral to inhibit fungal growth. These results
      indicate the potential use of citral as a natural pesticide control of post
      harvest fruit diseases. 

PMID- 24031198
TI  - Molecular analysis of the iap gene of Listeria monocytogenes isolated from
      cheeses in rio grande do Sul, Brazil.
AB  - The polymorphic region sequences in the iap gene were analyzed in 25 strains of
      Listeria monocytogenes isolated from cheeses in the state of Rio Grande do Sul,
      and compared with reference strains. This investigation distinguished two
      clusters of L. monocytogenes: I (20 strains) and II (5 strains). 

PMID- 24031199
TI  - Detection of Salmonella sp in chicken cuts using immunomagnetic separation.
AB  - The immunomagnetic separation (IMS) is a technique that has been used to increase
      sensitivity and specificity and to decrease the time required for detection of
      Salmonella in foods through different methodologies. In this work we report on
      the development of a method for detection of Salmonella in chicken cuts using in
      house antibody-sensitized microspheres associated to conventional plating in
      selective agar (IMS-plating). First, protein A-coated microspheres were
      sensitized with polyclonal antibodies against lipopolysacharide and flagella from
      salmonellae and used to standardize a procedure for capturing Salmonella
      Enteritidis from pure cultures and detection in selective agar. Subsequently,
      samples of chicken meat experimentally contaminated with S. Enteritidis were
      analyzed immediately after contamination and after 24h of refrigeration using
      three enrichment protocols. The detection limit of the IMS-plating procedure
      after standardization with pure culture was about 2x10 CFU/mL. The protocol using
      non-selective enrichment for 6-8h, selective enrichment for 16-18h and a post
      enrichment for 4h gave the best results of S. Enteritidis detection by IMS
      plating in experimentally contaminated meat. IMS-plating using this protocol was
      compared to the standard culture method for salmonellae detection in naturally
      contaminated chicken cuts and yielded 100% sensitivity and 94% specificity. The
      method developed using in house prepared magnetic microespheres for IMS and
      plating in selective agar was able to diminish by at least one day the time
      required for detection of Salmonella in chicken products by the conventional
      culture method. 

PMID- 24031200
TI  - Bacteriocin production by Lactobacillus plantarum AMA-K isolated from Amasi, a
      Zimbabwean fermented milk product and study of the adsorption of bacteriocin AMA
      K TO Listeria sp.
AB  - Bacteriocin AMA-K produced by Lactobacillus plantarum AMA-K inhibits the growth
      of Enterococcus spp., Escherichia coli, Klebsiella pneumoniae and Listeria spp.
      Growth of strain AMA-K in BHI, M17, soy milk and molasses was similar to growth
      in MRS. The effect of organic nitrogen sources, carbohydrates, glycerol, K2HPO4
      and KH2PO4, MgSO4, MnSO4, tri-ammonium citrate, Tween 80, vitamins and initial pH
      on bacteriocin AMA-K was determined. The mode of action of bacteriocin AMA-K was
      studied. The effect of bacteriocin AMA-K to actively growing Listeria innocua
      LMG13568, L. ivanovii subsp. ivanovii ATCC19119 and L. monocytogenes ScottA was
      determined. Adsorption of bacteriocin AMA-K to target cells at different
      temperatures, pH and in presence of Tween 20, Tween 80, ascorbic acid, potassium
      sorbate, sodium nitrate and sodium chloride were studied. Bacteriocin AMA-K
      shares high homology to pediocin PA-1. 

PMID- 24031201
TI  - Molecular characterization of Rhodococcus equi Isolates of horse breeding farms
      from an endemic region in South of Brazil by multiplex PCR.
AB  - Rhodococcus equi is a gram-positive coco-bacillus and an intracellular
      opportunistic pathogen which causes pneumonia in foals. It is widely detected in
      environment and has been isolated from several sources, as soil, feces and gut
      from health and sick foals. The goal of this study was to characterize the
      epidemiological status (endemic, sporadic or no infection) of horse breeding
      farms from Bage County in South of Brazil, using a multiplex PCR. One hundred and
      eighteen R. equi isolates were identified by biochemical tests and submitted to a
      specie-specific and vapA multiplex PCR. These isolates were obtained from: three
      farms where the R. equi infection has been noticed, two farms where the disease
      has been not reported and one farm where the disease is frequent. All clinical
      isolates from horse breeding farms where the disease is endemic and/or sporadic
      were vapA-positive. None environmental isolates were vapA-positive. In three
      horse breeding farms with sporadic R. equi infection, 11.54% of the isolates from
      adult horse feces were vapA-positive. The multiplex PCR technique has proven to
      be effective for the molecular and epidemiological characterization of the R.
      equi isolates in horse breeding farms. An important finding in this study was the
      isolation of vapApositive R. equi from adult horse feces, which is an evidence
      for other routes of dissemination of this pathogen in the farms. 

PMID- 24031203
TI  - Improved diagnosis of central nervous system tuberculosis by MPB64-Target PCR.
AB  - Central nervous system (CNS) tuberculosis is a serious clinical problem, the
      treatment of which is sometimes hampered by delayed diagnosis. Clearly, prompt
      laboratory diagnosis is of vital importance as the spectrum of disease is wide
      and abnormalities of the cerebrospinal fluid (CSF) are incredibly variable. Since
      delayed hypersensitivity is the underlying immune response, bacterial load is
      very low. The conventional bacteriological methods rarely detect Mycobacterium
      tuberculosis in CSF and are of limited use in diagnosis of tuberculous meningitis
      (TBM). This double blind study was, therefore, directed to the molecular analysis
      of CNS tuberculosis by an in-house-developed PCR targeted for amplification of a
      240bp nucleotide sequence coding for MPB64 protein specific for Mycobacterium
      tuberculosis. Based on the clinical criteria, 47 patients with CNS tuberculosis
      and a control group of 10 patients having non-tubercular lesions of the CNS were
      included in the study. Analyses were done in three groups; one group consisting
      of 27 patients of TBM, a second group of 20 patients with intracranial
      tuberculomas and a third group of 10 patients having nontubercular lesions of the
      CNS acted as control. There were no false positive results by PCR and the
      specificity worked out to be 100%. In the three study groups, routine CSF
      analysis (cells and chemistry), CSF for AFB smear and culture were negative in
      all cases. PCR was positive for 21/27 patients (77.7% sensitivity) of the first
      group of TBM patients, 6/20 patients (30% sensitivity) of the second group with
      intracranial tuberculomas were positive by PCR and none was PCR-positive (100%
      specificity) in the third group. Thus, PCR was found to be more sensitive than
      any other conventional method in the diagnosis of clinically suspected tubercular
      meningitis. 

PMID- 24031204
TI  - Lectin-binding properties of Aeromonas caviae strains.
AB  - The cell surface carbohydrates of four strains of Aeromonas caviae were analyzed
      by agglutination and lectin-binding assays employing twenty highly purified
      lectins encompassing all sugar specificities. With the exception of L-fucose and
      sialic acid, the sugar residues were detected in A. caviae strains. A marked
      difference, however, in the pattern of cell surface carbohydrates in different A.
      caviae isolates was observed. Specific receptors for Tritricum vulgaris (WGA),
      Lycopersicon esculentum (LEL) and Solanum tuberosum (STA) (D-GlcNAc-binding
      lectins) were found only in ATCC 15468 strain, whereas Euonymus europaeus (EEL, D
      Gal-binding lectin) sites were present exclusively in AeQ32 strain, those for
      Helix pomatia (HPA, D-GalNAc-binding lectin) in AeC398 and AeV11 strains, and for
      Canavalia ensiformes (Con A, D-Man-binding lectin) in ATCC 15468, AeC398, AeQ32
      and AeV11 strains, after bacterial growing at 37 degrees C. On the other hand,
      specific receptors for WGA and EEL were completely abrogated growing the bacteria
      at 22 degrees C. Binding studies with (125)I- labeled lectins from WGA, EEL and
      Con A were performed. These assays essentially confirmed the selectivity,
      demonstrated in the agglutination assays of these lectins for the A. caviae
      strains.

PMID- 24031202
TI  - Glycoconjugates and polysaccharides of fungal cell wall and activation of immune
      system.
AB  - Glycoproteins, glycosphingolipids and polysaccharides exposed at the most
      external layers of the wall are involved in several types of interactions of
      fungal cells with the exocellular environment. These molecules are fundamental
      building blocks of organisms, contributing to the structure, integrity, cell
      growth, differentiation and signaling. Several of them are immunologically active
      compounds with potential as regulators of pathogenesis and the immune response of
      the host. Some of these structures can be specifically recognized by antibodies
      from patients' sera, suggesting that they can be also useful in the diagnosis of
      fungal infections. 

PMID- 24031205
TI  - Membrane fluidity and lipid composition of fluconazole resistant and susceptible
      strains of Candida albicans isolated from diabetic patients.
AB  - Ten clinical isolates of Candida albicans, five strains belonging to each of
      fluconazole resistant and susceptible groups isolated from diabetic patients,
      were studied for the membrane fluidity and lipid composition. Compared to
      fluconazole susceptible strains, fluconazole resistant ones exhibited enhanced
      membrane fluidity as measured by fluorescence polarization technique. The
      increased membrane fluidity was reflected in the decreased p-values exhibited by
      the resistant strains. On the other hand, susceptible isolates contained higher
      amount of ergosterol, almost twice as compared to resistant isolates which might
      have contributed to their lower membrane fluidity. However, no significant
      alteration was observed in the phospholipid and fatty acid composition of these
      isolates. Labeling experiments with fluorescamine dye revealed that the
      percentage of the exposed aminophospholipid, phosphatidylethanolamine was highest
      in the resistant strains as compared to the susceptible strains, indicating a
      possible overexpression of CDR1 and CDR2 genes in resistant strains. The results
      presented here suggest that the changes in the ergosterol content and
      overexpression of ABC transporter genes CDR1 and CDR2 could contribute to
      fluconazole resistance in C. albicans isolated from diabetic patients. 

PMID- 24031206
TI  - Periodontal profile and presence of periodontal pathogens in young African
      Americans from Salvador, Ba, Brazil.
AB  - This cross-sectional study evaluated the periodontal status and the presence of
      periodontopathogens in 132 young, black ethnic subjects who live in
      Salvador/Bahia-Brazil and have never smoked. Periodontal Probing Depth (PPD),
      Clinical Attachment Level (CAL), Plaque Index (PI) and Gingival Index (GI) were
      measured and analyzed by ANOVA and Wilcoxon tests (p<0.05) according to gender
      and age. The presence of A.actinomycetemcomitans, P.gingivalis, E.corrodens and
      F.nucleatum was determined by PCR and was analyzed by ANOVA, Wilcoxon, Student-t
      tests (p<0.05). Mean values of PPD and CAL were 2.18 and 1.0mm, respectively.
      Clinical parameters did not show differences between subjects of varying gender
      and age. The microbial prevalence was observed to be 95.45% for E.corrodens
      followed by F.nucleatum with 68.18%, A.actinomycetemcomitans with 45.45% and P
      gingivalis with 40.9%. An association between the presence of pathogens and
      gender and age was not observed (p<0.05). PPD, CAL and PI were not associated
      with P.gingivalis; however, GI appeared in higher frequencies among subjects
      without P.gingivalis. In this young, black ethnic, Brazilian population, a high
      percentage (96.96%) of subjects harbored at least one selected periodontal
      pathogen, but most subjects showed a healthy periodontal status. Further
      investigations are required to evaluate the actual influence of the presence of
      these bacterial species. 

PMID- 24031207
TI  - In vitro synergistic activity of antibiotic combinations against Brucella
      melitensis using E-test methodology.
AB  - The treatment of brucellosis is still problematic, because of high rates of
      treatment failure or relapses. As the microorganism is an intracellular pathogen,
      treatment requires combined regimens. However, limited existing data on in vitro
      combinations are avaliable for Brucellae. The aim of this study was to
      investigate the in vitro efficacy of various traditional and new antibiotic
      combinations against 16 Brucella melitensis strains. The combination effect of
      antimicrobial agents was evaluated by E-test synergy method to obtain a
      fractional inhibitory concentration (FIC) index. Co-Trimoxazole (SXT) and
      moxifloxocin (MXF) exhibited the lowest MIC, while Rifampin (RIF) had the highest
      MIC in the study. Combinations with RIF showed the best synergistic activity
      (100% of RIF-tetracycline (TET), and 87.5% of RIF-SXT). Synergistic activity was
      also detected at seven (43.7%) of ciprofloxocin (CIP)-SXT, four (25%) of TET-MXF,
      and two (12.5%) of TET-SXT combinations. The combinations that demonstrated
      additivity were TET-SXT, CIP-SXT and TET-MXF. Antagonism was observed only with
      the TET-Streptomycin (STR) combination in three strains (18.8%). Further work
      including randomized controlled clinical trials is required to fully evaluate the
      usefulness of these data. 

PMID- 24031208
TI  - Lectin staining patterns in human gastric mucosae with and without exposure to
      Helicobacter pylori.
AB  - The aim of the present study was to evaluate qualitative changes in the
      glycoconjugate expression in human gastric tissue of positive and negative
      patients for Helicobacter pylori, through lectins: Wheat Germ Agglutinin (WGA)
      and Concanavalin A (Con A). The lectins recognized differently the
      glycoconjugates in the superficial mucous layer at the gastric tissues. The
      results suggest a significant change in the carbohydrate moieties present on the
      surface of the gastric cells during infection. 

PMID- 24031209
TI  - Comparison of three decontamination methods for Mycobacterium bovis isolation.
AB  - SIXTY SAMPLES OF TISSUE FRAGMENTS WITH LESIONS SUGGESTIVE OF TUBERCULOSIS FROM
      BOVINE ABATTOIRS, KEPT IN SATURATED SOLUTION OF SODIUM BORATE, WERE SUBJECTED TO
      FOUR TREATMENTS: 4% NaOH (Petroff Method), 12 % H2SO4 and 1.5% HPC (1
      Hexadecylpyridinium Chloride) decontamination, and physiological saline solution
      (control). The HPC method showed the lowest contamination rate (3%) when compared
      to control (88%, p<0.001), NaOH (33%, p<0.001) and H2SO4 (21.7%, p<0.002).
      Regarding the isolation success, the HPC method was better (40%) than the control
      (3%, p<0.001), NaOH (13%, p=0.001) and H2SO4 (1.7%, p<0.001) methods. These
      results indicate that HPC is an alternative to the Petroff method. 

PMID- 24031210
TI  - Antibiotic susceptibility patterns and prevalence of group B Streptococcus
      isolated from pregnant women in Misiones, Argentina.
AB  - This study was performed to determine the susceptibility patterns and the
      colonization rate of Group B Streptococcus (GBS) in a population of pregnant
      women. From January 2004 to December 2006, vaginal-rectal swabs were obtained
      from 1105 women attending Dr. Ramon Madariaga Hospital, in Posadas, Misiones,
      Argentina. The carriage rate of GBS among pregnant women was 7.6%. A total of 62
      GBS strains were randomly selected for in vitro susceptibility testing to
      penicillin G, ampicillin, tetracycline, levofloxacin, gatifloxacin,
      ciprofloxacin, quinupristin-dalfopristin, linezolid, vancomycin, rifampicin,
      trimethoprim- sulfametoxazol, nitrofurantoin, gentamicin, clindamycin and
      erythromycin, and determination of resistance phenotypes. No resistance to
      penicillin, ampicillin, quinupristin-dalfopristin, linezolid, and vancomycin was
      found. Of the isolates examined 96.8%, 98.3%, 46.8%, and 29.0% were susceptible
      to rifampicin, nitrofurantoin, trimethoprim-sulfametoxazol and tetracycline,
      respectively. Rank order of susceptibility for the quinolones was: gatifloxacin
      (98.4%) > levofloxacin (93.5%) > ciprofloxacin (64.5%). The rate of resistance to
      erythromycin (9.7%) was higher than that of other reports from Argentina. High
      level resistance to gentamicin was not detected in any of the isolates. Based on
      our finding of 50% of GBS isolates with MIC to gentamicin equal o lower than 8
      MUg/ml, a concentration used in one of the selective media recommended for GBS
      isolation, we suggested, at least in our population, the use of nalidixic acid
      and colistin in selective media with the aim to improve the sensitivity of
      screening cultures for GBS carriage in women. 

PMID- 24031211
TI  - Serological markers and risk factors related to hepatitis B virus in dentists in
      the Central West region of Brazil.
AB  - The hepatitis B virus (HBV) has been considered the major occupational risk agent
      for dentists. The Central West region of Brazil is considered an intermediate
      endemic pattern area, but currently there is no information about the HBV
      prevalence in dentists of Goiania, Goias. This study aimed at the detection of
      the HBV infection rate and risk factors for dentists of Goiania and the
      comparison of the obtained data with the general population and other groups. A
      randomized sample of 680 professionals participated in this study. All dentists
      gave written consent for the procedure and filled out a questionnaire about risk
      factors. The HBV serological markers were analyzed using ELISA test and the
      presence of anti-HBc was observed in 41 (6.0%) of the dentists. None of them was
      HBsAg positive. Significant relationships with HBV positivity were observed with
      gender, the time working as a dentist and the use of incomplete personal
      protective equipment (PPE). The HBV prevalence found in this group of dentists
      was lower than the endemic pattern of the general population, other health care
      workers of the region and the dentists from other regions in Brazil. These
      results may indicate a positive impact of vaccination considering the high
      adherence of the dentists to the immunization program (98.4%). Finally, the use
      of complete PPE by the majority as well as other standard precautions recommended
      for health care workers could be responsible for the low HBV seroprevalence. 

PMID- 24031212
TI  - Occurrence of yeasts, enterococci and other enteric bacteria in subgingival
      biofilm of HIV-positive patients with chronic gingivitis and necrotizing
      periodontitis.
AB  - The purpose of this study was to determine the prevalence of enteric bacteria and
      yeasts in biofilm of 80 HIV-positive patients with plaque-associated gingivitis
      or necrotizing periodontitis. Patients were subjected to extra, intra oral and
      radiographic examinations. The oral hygiene, bleeding on probing, gingival
      conditions, and attachment loss were evaluated. Clinical specimens were collected
      from gingival crevices or periodontal pockets, transferred to VMGA III, diluted
      and transferred to Sabouraud Dextrose agar with 100 MUg/ml of chloramphenicol,
      peptone water, EVA broth, EMB agar, SS agar, Bile esculin agar and Brilliant
      green agar. Isolation of yeasts was carried out at room temperature, for 3-7
      days; and for the isolation of enteric microorganisms plates were incubated at 37
      degrees C, for 24-48 h. The yeasts identification was performed according to the
      carbon and nitrogen assimilation, fermentation of carbohydrates and germ tube
      formation. Bacteria were identified according to their colonial and cellular
      morphologies and biochemical tests. Yeasts were identified as Candida albicans
      and its occurrence was more common in patients with CD4+ below 200/mm(3) and was
      affected by the extension of periodontal involvement (P = 0.0345). Enteric
      bacteria recovered from clinical specimens were identified as Enterobacter
      sakazakii, Enterobacter cloacae, Serratia liquefaciens, Klebsiella oxytoca and
      Enterococcus sp. Enterobacteriaceae and enterococci were detected in 32.5% of
      clinical samples from patients with necrotizing periodontitis. In conclusion, non
      oral pathogenic bacteria and C. albicans were more prevalent in periodontal sites
      of HIV-positive patients with necrotizing periodontitis and chronic gingivitis. 

PMID- 24031213
TI  - Comparison between qualitative and semiquantitative catheter-tip cultures:
      laboratory diagnosis of catheter-related infection in newborns.
AB  - This prospective study evaluated semiquantitative and qualitative catheter
      culture methods for diagnosis of catheter-related infection (CRI) in newborns.
      Catheter tips from newborns admitted to the Neonatal Unit of the University
      Hospital of the Botucatu Medical School, UNESP were included in the study.
      Catheter cultures were performed with both semiquantitative and qualitative
      techniques. For CRI diagnosis, microorganisms isolated from catheter cultures and
      from peripheral blood cultures were identified and submitted to agent
      susceptibility test. The gold standard was the certain CRI diagnosis when same
      microorganism (specie and profile of susceptibility to agents) was isolated from
      both catheter tips and peripheral blood culture. A total of 85 catheters from 63
      newborns were included in the study. The semiquantitative culture method, despite
      presenting lower sensitivity (90%), showed higher specificity (71%) when compared
      to 100% of sensitivity and 60% of specificity in the qualitative method. The
      identification of the microorganisms obtained from the catheter cultures showed a
      prevalence of coagulase-negative staphylococci (CNS) species. The specie
      Staphylococcus epidermidis (77.5%) was the prevalent in the catheters with
      positive semiquantitative cultures. Among 11 episodes with CRI diagnosis, 8
      (72.7%) were associated with CNS species, of which 6 were S. epidermidis. Two
      episodes of CRI by S. aureus and one by Candida parapsilosis were also detected.
      The semiquantitative catheter-culture method showed advantages for CRI diagnosis
      in newborns when compared to the conservative qualitative method. 

PMID- 24031214
TI  - Identification of non-tuberculous mycobacteria from the Central Public Health
      Laboratory from Mato Grosso do Sul and analysis of clinical relevance.
AB  - Non-tuberculous mycobacteria isolated at the Central Public Health Laboratory
      from Mato Grosso do Sul in 2003 and 2004 were identified by conventional
      phenotypic methods (TI) and by PCR-Restriction Enzyme Analysis (PRA) using the
      hsp65 gene as target (PRA-hsp65). With 15 of the 32 analysed isolates, results of
      both methods were concordant, being 8 Mycobacterium avium, 3 M. fortutium, 1 M.
      kansasii, 1 M. flavescens, 1 M. peregrinum and 1 Nocardia brasiliensis. TI of 12
      isolates was inconclusive. Novel PRA-hsp65 patterns were observed with 11
      isolates. Medical data were evaluated for inference of clinical relevance of
      these isolates. 

PMID- 24031215
TI  - Virulence factors in vancomycin-resistant and vancomycin- susceptible
      Enterococcus faecalis from Brazil.
AB  - Enterococci are members of commensal flora of animals and insects, but are also
      important opportunistic pathogens. Our objective was to observe if there was any
      difference of virulence in several groups of E. faecalis, mainly between
      vancomycin-resistant E. faecalis (VREFS) of colonization and infection. VREFS and
      vancomycin-sensitive E. faecalis from Brazil were screened for the presence of
      virulence factor genes. Phenotypic assays were used to assess in vitro
      expression, to understand the pathogenic potential of these isolates and to
      determine whether a correlation exists between virulence and antibiotic
      resistance. Different virulence profiles were found suggesting that the
      disseminating clone may have generated several variations. However, our study
      showed that one constellation of traits appeared most commonly: gelatinase,
      aggregation substance and esp (GEA). These factors are important because they
      have been implicated in cell aggregation and biofilm formation. Biofilm formation
      may promote the conjugation of plasmids harboring resistance and virulence genes,
      enhancing the probability of entry of new resistance genes into species.
      Curiously, the profile GEA was not exclusive to VREFS, it was the second most
      observed in VSEFS isolates from colonization and infection in hospitalized
      patients and also from rectal swabs of healthy volunteers. Such strains appear to
      represent the entry gateway to new resistance genes into E. faecalis and may
      contribute to the spreading of E. faecalis mainly in hospitals. 

PMID- 24031216
TI  - Candida Glabrata Esophagitis: new case reports and management.
AB  - Candida esophagitis (CE) is a common opportunistic infection in the
      immunocompromised host. C. glabrata is rarely cited as agent of CE and has been
      underestimated due to lack of proper identification. In this study, two cases of
      C. glabrata esophagitis in AIDS and chagasic patients are reported. Diagnosis of
      Candida species should be considered an important key for the ideal choice of
      antifungal therapy against this mycosis. 

PMID- 24031217
TI  - Occurrence of filamentous fungi in Simulium goeldii Cerqueira & Nunes de Mello
      (diptera: simuliidae) larvae in central Amazonia, Brazil.
AB  - The family Simuliidae is the host of simbiontes fungi that inhabit the digestive
      tracts of arthropods. This paper reports the presence of fungi in Simulium
      goeldii Cerqueira & Nunes de Mello larvae in Amazonia. We observed that the
      larvae are a good component of aquatic systems to isolate filamentous fungi. 

PMID- 24031218
TI  - Mechanisms and significance of fungicide resistance.
AB  - In this review article, we show that occurrence of fungicide resistance is one of
      the most important issues in modern agriculture. Fungicide resistance may be due
      to mutations of genes encoding fungicide targets (qualitative fungicide
      resistance) or to different mechanisms that are induced by sub-lethal fungicide
      stress. These mechanisms result in different and varying levels of resistance
      (quantitative fungicide resistance). We discuss whether or not extensive use of
      fungicides in agricultural environments is related to the occurrence of fungicide
      resistance in clinical environments. Furthermore, we provide recommendations of
      how development of fungicide resistant pathogen populations may be prevented or
      delayed. 

PMID- 24031219
TI  - Greenhouse evaluation of Bacillus subtilis AP-01 and Trichoderma harzianum AP-001
      in controlling tobacco diseases.
AB  - Two biological control agents, Bacillus subtilis AP-01 (Larminar(TM)) and
      Trichoderma harzianum AP-001 (Trisan(TM)) alone or/in combination were
      investigated in controlling three tobacco diseases, including bacterial wilt
      (Ralstonia solanacearum), damping-off (Pythium aphanidermatum), and frogeye leaf
      spot (Cercospora nicotiana). Tests were performed in greenhouse by soil
      sterilization prior to inoculation of the pathogens. Bacterial-wilt and damping
      off pathogens were drenched first and followed with the biological control agents
      and for comparison purposes, two chemical fungicides. But for frogeye leaf spot,
      which is an airborne fungus, a spraying procedure for every treatment including a
      chemical fungicide was applied instead of drenching. Results showed that neither
      B. subtilis AP-01 nor T harzianum AP-001 alone could control the bacterial wilt,
      but when combined, their controlling capabilities were as effective as a chemical
      treatment. These results were also similar for damping-off disease when used in
      combination. In addition, the combined B. subtilis AP-01 and T. harzianum AP-001
      resulted in a good frogeye leaf spot control, which was not significantly
      different from the chemical treatment. 

PMID- 24031220
TI  - Cuticle-degrading proteases produced by the entomopathogenic fungus Beauveria
      bassiana in the presence of coffee berry borer cuticle.
AB  - A Brazilian isolate of Beauveria bassiana (CG425) that shows high virulence
      against the coffee berry borer (CBB) was examined for the production of
      subtilisin-like (Pr1) and trypsin-like (Pr2) cuticle-degrading proteases. Fungal
      growth was either in nitrate-medium or in CBB cuticle-containing medium under
      both buffered and unbuffered conditions. In unbuffered medium supplemented with
      cuticle, the pH of cultures dropped and Pr1 and Pr2 activities were detected in
      high amounts only at a pH of 5.5 or higher. In buffered cultures, Pr1 and Pr2
      activities were higher in medium supplemented with cuticle compared to activities
      with nitrate-medium. The Pr1 and Pr2 activities detected were mostly in the
      culture supernatant. These data suggest that Pr1 and Pr2 proteases produced by
      strain CG425 are induced by components of CBB cuticle, and that the culture pH
      influences the expression of these proteases, indicating the occurrence of an
      efficient mechanism of protein secretion in this fungus. The results obtained in
      this study extend the knowledge about protease production in B. bassiana CG425,
      opening new avenues for studying the role of secreted proteases in virulence
      against the coffee berry borer during the infection process. 

PMID- 24031221
TI  - A conservative region of the mercuric reductase gene (mera) as a molecular marker
      of bacterial mercury resistance.
AB  - The most common bacterial mercury resistance mechanism is based on the reduction
      of Hg(II) to Hg(0), which is dependent of the mercuric reductase enzyme (MerA)
      activity. The use of a 431 bp fragment of a conservative region of the mercuric
      reductase (merA) gene was applied as a molecular marker of this mechanism,
      allowing the identification of mercury resistant bacterial strains. 

PMID- 24031222
TI  - Fate of organochlorine (14)C-dicofol in a lab-scale wastewater treatment.
AB  - The fate of organochlorine (14)C-dicofol in activated sludge process was
      investigated. Results showed that the major part of radioactivity remained
      adsorbed on biological sludge. Consequently, its final disposal deserves special
      attention. The small amounts of dicofol, biotransformed or not, which remained in
      the treated effluent could contaminate receiving bodies. 

PMID- 24031223
TI  - Isolation and characterization of a chitinase gene from entomopathogenic fungus
      Verticillium lecanii.
AB  - Entomopathogenic fungus Verticillium lecanii is a promising whitefly and aphid
      control agent. Chitinases secreted by this insect pathogen have considerable
      importance in the biological control of some insect pests. An endochitinase gene
      Vlchit1 from the fungus was cloned and overexpressed in Escherichia coli. The
      Vlchit1 gene not only contains an open reading frame (ORF) which encodes a
      protein of 423 amino acids (aa), but also is interrupted by three short introns.
      Vlchit1 protein showed that the chitinase Vlchit1 has a (a/b)8 TIM barrel
      structure. Overexpression test and Enzymatic activity assay indicated that the
      Vlchit1 is a functional enzyme that can hydrolyze the chitin substrate, so the
      Vlchit1 gene can service as a useful gene source for genetic manipulation leading
      to strain improvement of entomopathogenic fungi or constructing new transgenic
      plants with resistance to various fungal and insects pests. 

PMID- 24031224
TI  - First record of Botryosphaeria ribis associated with leaf spots on Magnolia aff.
      candollei in Brazil.
AB  - A leaf spot disease was observed attacking some Magnolia aff. candollei plants
      grown in a private garden in the city of Rio de Janeiro, RJ, Brazil. Such leaf
      spots coalesced and led to extensive blight of foliage. A fungus was clearly
      associated to the disease symptoms and was identified as Botryosphaeria ribis.
      Its anamorph, Fusicoccum ribis, was also present, although less abundant than the
      teleomorph. This is first report of this fungus on this host in Brazil and the
      first record of any fungal disease on a member of the genus Magnolia in Brazil. 

PMID- 24031225
TI  - Effects of pH and temperature on growth and glycerol production kinetics of two
      indigenous wine strains of Saccharomyces cerevisiae from Turkey.
AB  - The study was performed in a batch system in order to determine the effects of pH
      and temperature on growth and glycerol production kinetics of two indigenous wine
      yeast strains Saccharomyces cerevisiae Kalecik 1 and Narince 3. The highest
      values of dry mass and specific growth rate were obtained at pH 4.00 for both of
      the strains. Maximum specific glycerol production rates were obtained at pH 5.92
      and 6.27 for the strains Kalecik 1 and Narince 3, respectively. Kalecik 1 strain
      produced maximum 8.8 gL(-1) of glycerol at pH 6.46. Maximum glycerol
      concentration obtained by the strain Narince 3 was 9.1 gL(-1) at pH 6.48. Both
      yeasts reached maximum specific growth rate at 30 degrees C. Optimum temperature
      range for glycerol production was determined as 25-30 degrees C for the strain
      Kalecik 1. The strain Narince 3 reached maximum specific glycerol production rate
      at 30 degrees C. Maximum glycerol concentrations at 30 degrees C were obtained as
      8.5 and 7.6 gL(-1) for Kalecik 1 and Narince 3, respectively. 

PMID- 24031226
TI  - Xylitol production from wheat straw hemicellulosic hydrolysate: hydrolysate
      detoxification and carbon source used for inoculum preparation.
AB  - Wheat straw hemicellulosic hydrolysate was used for xylitol bioproduction. The
      use of a xylose-containing medium to grow the inoculum did not favor the
      production of xylitol in the hydrolysate, which was submitted to a previous
      detoxification treatment with 2.5% activated charcoal for optimized removal of
      inhibitory compounds. 

PMID- 24031227
TI  - Chlorine dioxide against bacteria and yeasts from the alcoholic fermentation.
AB  - The ethanol production in Brazil is carried out by fed-batch or continuous
      process with cell recycle, in such way that bacterial contaminants are also
      recycled and may be troublesome due to the substrate competition. Addition of
      sulphuric acid when inoculum cells are washed can control the bacterial growth or
      alternatively biocides are used. This work aimed to verify the effect of chlorine
      dioxide, a well-known biocide for bacterial decontamination of water and
      equipments, against contaminant bacteria (Bacillus subtilis, Lactobacillus
      plantarum, Lactobacillus fermentum and Leuconostoc mesenteroides) from alcoholic
      fermentation, through the method of minimum inhibitory concentration (MIC), as
      well as its effect on the industrial yeast inoculum. Lower MIC was found for B.
      subtilis (10 ppm) and Leuconostoc mesenteroides (50 ppm) than for Lactobacillus
      fermentum (75 ppm) and Lactobacillus plantarum (125 ppm). Additionally, these
      concentrations of chlorine dioxide had similar effects on bacteria as 3 ppm of
      Kamoran(r) (recommended dosage for fermentation tanks), exception for B.
      subtilis, which could not be controlled at this Kamoran(r) dosage. The growth of
      industrial yeasts was affected when the concentration of chlorine dioxide was
      higher than 50 ppm, but the effect was slightly dependent on the type of yeast
      strain. Smooth yeast colonies (dispersed cells) seemed to be more sensitive than
      wrinkled yeast colonies (clustered cells/pseudohyphal growth), both isolated from
      an alcohol-producing unit during the 2006/2007 sugar cane harvest. The main
      advantage in the usage of chlorine dioxide that it can replace antibiotics,
      avoiding the selection of resistant populations of microorganisms. 

PMID- 24031228
TI  - Mycelial glucoamylases produced by the thermophilic fungus Scytalidium
      thermophilum strains 15.1 and 15.8: purification and biochemical
      characterization.
AB  - Two strains (15.1 and 15.8) of the thermophilic fungus Scytalidium thermophilum
      produced high levels of intracellular glucoamylases, with potential for
      industrial applications. The isoform I of the glucoamylase produced by 15.1
      strain was sequentially submitted to DEAE-Cellulose and CM-Cellulose
      chromatography, and purified 141-fold, with 5.45% recovery. The glucoamylase of
      strain 15.8 was purified 71-fold by CM- Cellulose and Concanavalin A-Sepharose
      chromatography, with 7.38% recovery. Temperature and pH optima were in the range
      of 50-60 degrees C and 5.0-6.0, respectively, using starch and maltose as
      substrates. The glucoamylase of S. thermophilum 15.8 was more stable (t50 > 60
      min) than that of S. thermophilum 15.1 (t50= 11-15 min), at 60 degrees C. The
      glucoamylase activities were enhanced by several ions (e.g. Mn(2+) and Ca(2+))
      and inhibited by beta- mercaptoethanol. The glucoamylase from 15.1 strain showed
      a Km of 0.094 mg/ml and 0.029 mg/ml and Vmax of 202 U/mg prot and 109 U/mg prot,
      for starch and maltose, respectively. The hydrolysis products of starch and
      maltose, analyzed by TLC, demonstrated glucose as end product and confirming the
      character of the enzyme as glucoamylase. Differences were observed in relation to
      the products formed with maltose as substrate between the two strains studied. S.
      thermophilum 15.8 formed maltotriose in contrast with S. thermophilum 15.1. 

PMID- 24031229
TI  - Mass spectrometry analysis of surface tension reducing substances produced by a
      pah-degrading Pseudomonas citronellolis strain.
AB  - In this work we investigated the structure of the iron-stimulated surface tension
      reducing substances produced by P. citronellolis 222A isolated from a 17-years
      old landfarming used for sludge treatment in petrochemical industries and oil
      refinery. Its mass spectrum differs from P. aeruginosa spectrum, indicating that
      the surface tension reducing substances produced by P. citronellolis can be a new
      kind of biosurfactant. 

PMID- 24031230
TI  - Evaluation of culture media for counts of Bifidobacterium animalis subsp. lactis
      Bb 12in yoghurt after refrigerated storage.
AB  - The agar RCPB pH5 has been considered a good alternative for counts of
      Bifidobacterium in yoghurt. However, during the refrigerated storage of yoghurt
      it is extremely difficult to count this microorganism due to the size of the
      colonies, which are so small they require the aid of a stereoscope to count them.
      Another agar, MRS-LP, has been also recommended for counts of Bifidobacterium in
      the presence of yoghurt bacteria. This study evaluated the supplementation of
      RCPB pH5 agar with dehydrated liver extract and the salts KH2PO4, K2HPO4,
      FeSO47H2O, MnSO4H2O and MgSO47H2O, aiming at improving the differentiation of
      Bifidobacterium in yoghurt after refrigerated storage, and also evaluated the
      selective count of Bifidobacterium in yoghurt using the agar MRS-LP. The agar MRS
      LP presented the same cell recovery as non-fortified RCPB pH5 agar, used as a
      standard medium, thus being considered a good option for counts of
      Bifidobacterium in yoghurt. The fortified RCPB pH5 also presented the same
      recovery as the standard RCPB pH5 medium, however, the addition of dehydrated
      liver extract to the RCPB pH5 agar considerably increased the size of the
      Bifidobacterium colonies after refrigerated storage, making differentiation of
      the colonies much easier and reliable when compared to the standard non-fortified
      RPCP pH5. The addition of the salts (KH2PO4, K2HPO4, FeSO47H2O, MnSO4H2O and
      MgSO47H2O) had no influence on the performance of the RCPB pH5 agar. 

PMID- 24031231
TI  - The potential of Origanum vulgare L. (Lamiaceae) essential oil in inhibiting the
      growth of some food-related Aspergillus species.
AB  - Origanum vulgare L. (Lamiaceae) has been currently known for their interesting
      antimicrobial activity being regarded as alternative antimicrobial for use is
      food conservation systems. This study aimed to evaluate the effectiveness of O.
      vulgare essential oil in inhibiting the growth of some food-related Aspergillus
      species (A. flavus, A. parasiticus, A. terreus, A. ochraceus, A. fumigatus and A.
      niger). The essential oil revealed a strong anti-Aspergillus property providing
      an inhibition of all assayed mould strains. MIC values were between 80 and 20
      MUL/mL being found a MIC50 of 40 MUL/mL. The essential oil at concentration of 80
      and 40 MUL/mL provided a fungicidal effect on A. flavus, A. fumigatus and A.
      niger noted by a total inhibition of the radial mycelial growth along 14 days of
      interaction. In addition, the essential oil was able to inhibit the mould spores
      germination when assayed at concentrations of 80 and 40 MUL/mL. Our results
      showed the interesting anti-Aspergillus activity of O. vulgare essential oil
      supporting their possible use as anti-mould compound in food conservation. 

PMID- 24031232
TI  - Screening of lactic acid bacteria from vacuum packaged beef for antimicrobial
      activity.
AB  - The objective of this study was to isolate lactic acid bacteria (LAB) from vacuum
      packaged beef and to investigate their antagonist activity. LAB mean counts of
      5.19 log cfu/cm(2) were obtained from five samples of vacuum packaged beef. Two
      hundred isolates were selected and screened for the inhibitory effect on five
      ATCC reference Lactobacillus strains. Thirty six isolates showed activity in the
      agar spot test against at least two of the indicator strains. However, only six
      cell free supernatants (CFS) from these isolates exhibited activity against the
      indicator strains using the well-diffusion test and conditions that eliminated
      the effects of organic acids and hydrogen peroxide. L. acidophilus was the most
      sensitive indicator tested, whereas L. plantarum and L. fermentum were the most
      resistant ones. Identification by MIDI system indicated that these LAB isolates
      were Lactococcus lactis subsp. cremoris, Pediococcus acidilactici, Lactobacillus
      delbrueckii subsp. bulgaricus and Lactobacillus casei GC subgroup A. The
      antagonistic factors produced by most of these LAB against L. acidophilus were
      resistant to heat treatment (100 degrees C for 10 min) and stable over a wide pH
      range (4.0 to 9.0). These data suggest that these isolates could be used as
      promising hurdles aiming increased safety and extended shelf life of meat
      products. 

PMID- 24031233
TI  - Epidemiological Survey of Listeria monocytogenes in a gravlax salmon processing
      line.
AB  - Listeria monocytogenes is a cause of concern to food industries, mainly for those
      producing ready-to-eat (RTE) products. This microorganism can survive processing
      steps such as curing and cold smoking and is capable of growing under
      refrigeration temperatures. Its presence in RTE fish products with extended shelf
      life may be a risk to the susceptible population. One example of such a product
      is gravlax salmon; a refrigerated fish product not exposed to listericidal
      processes and was the subject of this study. In order to evaluate the incidence
      and dissemination of L. monocytogenes 415 samples were collected at different
      steps of a gravlax salmon processing line in Sao Paulo state, Brazil. L.
      monocytogenes was confirmed in salmon samples (41%), food contact surfaces (32%),
      non-food contact surfaces (43%) and of food handlers' samples (34%), but could
      not be detected in any ingredient. 179 L. monocytogenes isolates randomly
      selected were serogrouped and typed by PFGE. Most of L. monocytogenes strains
      belonged to serogroup 1 (73%). 61 combined pulsotypes were found and a dendrogram
      identified six clusters: most of the strains (120) belonged to cluster A. It was
      suggested that strains arriving into the plant via raw material could establish
      themselves in the processing environment contaminating the final product. The
      wide dissemination of L. monocytogenes in this plant indicates that a great
      effort has to be taken to eliminate the microorganism from these premises, even
      though it was not observed multiplication of the microorganism in the final
      product stored at 4 degrees C up to 90 days. 

PMID- 24031234
TI  - Mycoplasma synoviae infection on Newcastle disease vaccination of chickens.
AB  - Newcastle disease is characterized by respiratory manifestations in association
      with nervous and/or digestive symptoms. Its prevention is done by vaccination
      with live attenuated (lentogenic strains) and/or killed vaccines. The lentogenic
      strains can lead to strong post-vaccination reaction, principally due to the
      presence of other pathogenic agents. Among them, Mycoplasma synoviae is worldwide
      important, mainly in Brazil. The dissemination of this agent in poultry flocks
      has been achieved due to difficulties in diagnosis and disease reproduction,
      virulence variations among different M.synoviae strains, and attribution of
      typical M.synoviae disease manifestation to other disease agents. This
      experimental study in SPF chicks (Gallus gallus), previously infected by
      M.synoviae and thereafter vaccinated against Newcastle disease, was done with the
      objective of evaluating M.synoviae pathogenicity through assessment of post
      vaccinal respiratory reactions and serologic responses to Newcastle disease virus
      vaccine in the absence of environmental factors. A total of 86 three days old
      chicks were used, being 57 infected by eye and nostril drop, with chicken
      activated M. synoviae strain WVU 1853. Seven days later, 21 mycoplasma infected
      birds plus 29 not mycoplasma infected ones were vaccinated against Newcastle
      disease. As results, the not infected and vaccinated birds yielded,
      significantly, higher and longer lasting serologic responses to Newcastle disease
      vaccine virus than those infected and vaccinated. Similarly, the infected and
      vaccinated birds yielded lower serologic reactions to M.synoviae than those only
      mycoplasma infected. No post-vaccinal respiratory reaction was observed in the
      vaccinated birds. 

PMID- 24031235
TI  - Control of Salmonella enterica serovar Enteritidis in laying hens by inactivated
      Salmonella Enteritidis vaccines.
AB  - Salmonella Enteritidis is one of the agents that is responsible for outbreaks of
      human foodborne salmonellosis caused by Salmonella Enteritidis and is generally
      associated with the consumption of poultry products. Inactivated Salmonella
      Enteritidis cell vaccine is one of the available methods to control Salmonella
      Enteritidis in breeders and laying hens, however results in terms of efficacy
      vary. This vaccine has never been tested in Brazil, therefore, the present work
      was carried out to assess three commercial inactivated Salmonella Enteritidis
      vaccines allowed in Brazil. Four hundred white light variety commercial laying
      hens were obtained at one-day-of age. At eight weeks old, the birds were divided
      into four groups with one hundred animals each. Birds from three groups (V1, V2
      and V3) received different intramuscular vaccines, followed by a booster dose at
      16 weeks of age. Birds from another group (CG) were not vaccinated. When the
      laying hens were 20, 25 and 31 weeks old, 13 from each group were transferred to
      another room and were challenged by inoculating 2 mL neat culture of Salmonella
      Enteritidis. On the second day after each challenge, the caecal contents, spleen,
      liver and ovary of three birds from each group were analyzed for the presence of
      Salmonella Enteritidis. Twice a week a cloacal swab of each bird was taken and
      all eggs laid were examined for the presence of Salmonella Enteritidis. After
      four consecutive negative cloacal swabs in all the groups, the birds were
      sacrificed so as to examine the liver, caecal contents and ovaries. Overall, the
      inactivated vaccine used in group V3 reduced Salmonella Enteritidis in the feces
      and eggs. A very small amount of Salmonella was found in the spleen, liver, ovary
      and caeca of the birds in the four groups during the whole experiment. In
      general, inactivated Salmonella Enteritidis vaccines was able to decrease the
      presence of Salmonella Enteritidis in the birds and in the eggs as well.
      Nevertheless, they must be associated with general hygiene and disinfection
      practices in poultry husbandry. 

PMID- 24031236
TI  - Antibacterial activities of multi drug resistant Myroides odoratimimus bacteria
      isolated from adult flesh flies (Diptera: sarcophagidae) are independent of
      metallo beta-lactamase gene.
AB  - FLESH FLIES (DIPTERA: Sarcophagidae) are well known cause of myiasis and their
      gut bacteria have never been studied for antimicrobial activity against bacteria.
      Antimicrobial studies of Myroides spp. are restricted to nosocomial strains. A
      Gram-negative bacterium, Myroides sp., was isolated from the gut of adult flesh
      flies (Sarcophaga sp.) and submitted to evaluation of nutritional parameters
      using Biolog GN, 16S rRNA gene sequencing, susceptibility to various
      antimicrobials by disc diffusion method and detection of metallo beta-lactamase
      genes (TUS/MUS). The antagonistic effects were tested on Gram-negative and Gram
      positive bacteria isolated from human clinical specimens, environmental samples
      and insect mid gut. Bacterial species included were Aeromonas hydrophila, A.
      culicicola, Morganella morganii subsp. sibonii, Ochrobactrum anthropi, Weissella
      confusa, Escherichia coli, Ochrobactrum sp., Serratia sp., Kestersia sp.,
      Ignatzschineria sp., Bacillus sp. The Myroides sp. strain was resistant to
      penicillin-G, erythromycin, streptomycin, amikacin, kanamycin, gentamycin,
      ampicillin, trimethoprim and tobramycin. These strain showed antibacterial action
      against all bacterial strains except W. confusa, Ignatzschineria sp., A.
      hydrophila and M. morganii subsp. sibonii. The multidrug resistance of the strain
      was similar to the resistance of clinical isolates, inhibiting growth of bacteria
      from clinical, environmental and insect gut samples. The metallo beta-lactamase
      (TUS/MUS) genes were absent, and resistance due to these genes was ruled out,
      indicating involvement of other secretion machinery.

PMID- 24031237
TI  - Selection of filamentous fungi of the Beauveria genus able to metabolize
      quercetin like mammalian cells.
AB  - Microbial biotransformations constitute an important alternative as models for
      drug metabolism study in mammalians and have been used for the industrial
      synthesis of chemicals with pharmaceutical purposes. Several microorganisms with
      unique biotransformation ability have been found by intensive screening and put
      in commercial applications. Ten isolates of Beauveria sp genus filamentous fungi,
      isolated from soil in the central Brazil, and Beauveria bassiana ATCC 7159 were
      evaluated for their capability of quercetin biotransformation. Biotransformation
      processes were carried out for 24 up to 96 hours and monitored by mass
      spectrometry analyses of the culture broth. All strains were able to metabolize
      quercetin, forming mammalian metabolites. The results were different from those
      presented by other microorganisms previously utilized, attrackting attention
      because of the great diversity of reactions. Methylated, sulphated,
      monoglucuronidated, and glucuronidated conjugated metabolites were simultaneously
      detected. 

PMID- 24031238
TI  - Evaluation of pasture soil productivity in the semi-arid zone of Brazil by
      microbial analyses.
AB  - The productivity of a pasture soil (caatinga) located in the region of Sao Joao
      do Cariri, PB, Brazil was evaluated based an the following microbiological
      parameters: biomass (measured by fumigation-incubation method), activity
      (estimated from basal respiration and cellulose decomposition rate), qCO2, and
      Cmic : Corg ratio. This analysis demonstrated that livestock management in the
      'caatinga' is probably causing environment damage by affecting the soil
      properties, reducing the microbial biomass and soil respiration and increasing
      the qCO2, affecting the recovery of this ecosystem. 

PMID- 24031239
TI  - Molecular characterization of nitrogen-fixing bacteria isolated from brazilian
      agricultural plants at Sao Paulo state.
AB  - Fourteen strains of nitrogen-fixing bacteria were isolated from different
      agricultural plant species, including cassava, maize and sugarcane, using
      nitrogen-deprived selective isolation conditions. Ability to fix nitrogen was
      verified by the acetylene reduction assay. All potentially nitrogen-fixing
      strains tested showed positive hybridization signals with a nifH probe derived
      from Azospirillum brasilense. The strains were characterized by RAPD, ARDRA and
      16S rDNA sequence analysis. RAPD analyses revealed 8 unique genotypes, the
      remaining 6 strains clustered into 3 RAPD groups, suggesting a clonal origin.
      ARDRA and 16S rDNA sequence analyses allowed the assignment of 13 strains to
      known groups of nitrogen-fixing bacteria, including organisms from the genera
      Azospirillum, Herbaspirillum, Pseudomonas and Enterobacteriaceae. Two strains
      were classified as Stenotrophomonas ssp. Molecular identification results from
      16S rDNA analyses were also corroborated by morphological and biochemical data. 

PMID- 24031240
TI  - Comparison of plant growth-promotion with Pseudomonas aeruginosa and Bacillus
      subtilis in three vegetables.
AB  - Our objective was to compare some plant growth promoting rhizobacteria (PGPR)
      properties of Bacillus subtilis and Pseudomonas aeruginosa as representatives of
      their two genera. Solanum lycopersicum L. (tomato), Abelmoschus esculentus
      (okra), and Amaranthus sp. (African spinach) were inoculated with the bacterial
      cultures. At 60 days after planting, dry biomass for plants treated with B.
      subtilis and P. aeruginosa increased 31% for tomato, 36% and 29% for okra, and
      83% and 40% for African spinach respectively over the non-bacterized control.
      Considering all the parameters tested, there were similarities but no significant
      difference at P < 0.05 between the overall performances of the two organisms. 

PMID- 24031241
TI  - Bioconversion of petroleum hydrocarbons in soil using apple filter cake.
AB  - The aim of this study was to investigate the feasibility of using apple filter
      cake, a fruit-processing waste to enhance the bioremediation of petroleum
      contaminated soil. A rotating barrel system was used to study the bioconversion
      of the xenobiotic compound by natural occurring microbial population. The soil
      had been accidentally polluted with a total petroleum hydrocarbon concentration
      of 41,000 ppm. Although this global value was maintained during the process,
      microbial intervention was evidenced through transformation of the petroleum
      fractions. Thus, fractions that represent a risk for the environment (GRO,
      Gasoline Range Organics i.e., C6 to C10-12; DRO, Diesel Range Organics i.e., C8
      12 to C24-26 and RRO, Residual Range Organics i.e., C25 to C35) were
      significantly reduced, from 2.95% to 1.39%. On the contrary, heavier weight
      fraction from C35 plus other organics increased in value from 1.15% to 3.00%. The
      noticeable diminution of low molecular weight hydrocarbons content and hence
      environmental risk by the process plus the improvement of the physical
      characteristics of the soil, are promising results with regard to future
      application at large scale. 

PMID- 24031242
TI  - Molecular cloning of chitinase 33 (chit33) gene from Trichoderma atroviride.
AB  - In this study Trichoderma atroviride was selected as over producer of chitinase
      enzyme among 30 different isolates of Trichoderma sp. on the basis of chitinase
      specific activity. From this isolate the genomic and cDNA clones encoding chit33
      have been isolated and sequenced. Comparison of genomic and cDNA sequences for
      defining gene structure indicates that this gene contains three short introns and
      also an open reading frame coding for a protein of 321 amino acids. The deduced
      amino acid sequence includes a 19 aa putative signal peptide. Homology between
      this sequence and other reported Trichoderma Chit33 proteins are discussed. The
      coding sequence of chit33 gene was cloned in pEt26b(+) expression vector and
      expressed in E. coli. 

PMID- 24031243
TI  - Control of brown spot pathogen of rice (Bipolaris oryzae) using some phenolic
      antioxidants.
AB  - Bipolaris oryzae is the causal agent of rice brown spot disease and is
      responsible for significant economic losses. In order to control this disease,
      three phenolic antioxidants were tested (salicylic acid, benzoic acid and
      hydroquinone). The antifungal activity of the tested substances were investigated
      against B. oryzae at different concentrations in vitro, as well as the efficacy
      of their exogenous application in controlling rice brown spot disease under field
      conditions. In vitro, benzoic acid or salicylic acid at 9 mM completely inhibited
      the growth of B. oryzae. Under field conditions, spraying of benzoic acid at 20
      mM led to a significant reduction in disease severity (DS) and disease incidence
      (DI) on the plant leaves, in addition to a significant increase in the grain
      yield and its components. Some biochemical responses were also detected, where
      the application of the previous treatment led to a significant increase in the
      total photosynthetic pigments (chlorophyll a and b and carotenoids) in rice
      leaves and in the total carbohydrate and protein contents of the yielded grains. 

PMID- 24031245
TI  - Microbial populations of crude oil spill polluted soils at the Jordan-Iraq desert
      (the Badia region).
AB  - Microbial populations' inhabitants in crude petroleum contaminated soils were
      analyzed in relation with the soil characteristics. A noticeable greater decline
      of bacterial counts and diversity but a prevalence of the genus Pseudomonas over
      the other identified genera in the fresh contaminated soils as compared to the
      old ones was observed. 

PMID- 24031244
TI  - Bacterial diversity characterization in petroleum samples from Brazilian
      reservoirs.
AB  - This study aimed at evaluating potential differences among the bacterial
      communities from formation water and oil samples originated from biodegraded and
      non-biodegraded Brazilian petroleum reservoirs by using a PCR-DGGE based
      approach. Environmental DNA was isolated and used in PCR reactions with bacterial
      primers, followed by separation of 16S rDNA fragments in the DGGE. PCR products
      were also cloned and sequenced, aiming at the taxonomic affiliation of the
      community members. The fingerprints obtained allowed the direct comparison among
      the bacterial communities from oil samples presenting distinct degrees of
      biodegradation, as well as between the communities of formation water and oil
      sample from the non-biodegraded reservoir. Very similar DGGE band profiles were
      observed for all samples, and the diversity of the predominant bacterial
      phylotypes was shown to be low. Cloning and sequencing results revealed major
      differences between formation water and oil samples from the non-biodegraded
      reservoir. Bacillus sp. and Halanaerobium sp. were shown to be the predominant
      components of the bacterial community from the formation water sample, whereas
      the oil sample also included Alicyclobacillus acidoterrestris, Rhodococcus sp.,
      Streptomyces sp. and Acidithiobacillus ferrooxidans. The PCR-DGGE technique,
      combined with cloning and sequencing of PCR products, revealed the presence of
      taxonomic groups not found previously in these samples when using cultivation
      based methods and 16S rRNA gene library assembly, confirming the need of a
      polyphasic study in order to improve the knowledge of the extent of microbial
      diversity in such extreme environments. 

PMID- 24031246
TI  - Nitrogen starvation affects bacterial adhesion to soil.
AB  - One of the main factors limiting the bioremediation of subsoil environments based
      on bioaugmentation is the transport of selected microorganisms to the
      contaminated zones. The characterization of the physiological responses of the
      inoculated microorganisms to starvation, especially the evaluation of
      characteristics that affect the adhesion of the cells to soil particles, is
      fundamental to anticipate the success or failure of bioaugmentation. The
      objective of this study was to investigate the effect of nitrogen starvation on
      cell surface hydrophobicity and cell adhesion to soil particles by bacterial
      strains previously characterized as able to use benzene, toluene or xilenes as
      carbon and energy sources. The strains LBBMA 18-T (non-identified), Arthrobacter
      aurescens LBBMA 98, Arthrobacter oxydans LBBMA 201, and Klebsiella sp. LBBMA 204
      1 were used in the experiments. Cultivation of the cells in nitrogen-deficient
      medium caused a significant reduction of the adhesion to soil particles by all
      the four strains. Nitrogen starvation also reduced significantly the strength of
      cell adhesion to the soil particles, except for Klebsiella sp. LBBMA 204-1. Two
      of the four strains showed significant reduction in cell surface hydrophobicity.
      It is inferred that the efficiency of bacterial transport through soils might be
      potentially increased by nitrogen starvation. 

PMID- 24031247
TI  - Population densities and genetic diversity of actinomycetes associated to the
      rhizosphere of Theobroma cacao.
AB  - In spite of the acknowledged importance of growth-promoting bacteria, only a
      reduced number of studies were conducted with these microorganisms on Theobroma
      cacao. The objectives of this work were to study the population densities and
      genetic diversity of actinomycetes associated with the rhizosphere of cacao as a
      first step in their application in plant growth promotion and biological control.
      The populations densities of actinomycetes in soil and cacao roots were similar,
      with mean values of 1,0 x 10(6) CFU/g and 9,6 x 10(5) CFU/g, respectively. All
      isolates selected and used in this study were identified through sequencing
      analyses of a fragment of the rpoB gene that encodes the beta-subunit of the RNA
      polymerase as species of the genus Streptomyces. In vitro cellulolytic,
      xilanolytic and chitinolytic activity, indolacetic acid production and phosphate
      solubilization activities were observed in most of the isolates tested. The data
      obtained in this study demonstrate that actinomycetes account for a higher
      percentage of the total population of culturable bacteria in soil than on cacao
      roots. Additionally, actinomycetes from the cacao rhizosphere are genetically
      diverse and have potential applications as agents of growth promotion. 

PMID- 24031248
TI  - Detection of Mycoplasma hyopneumoniae by polymerase chain reaction in swine
      presenting respiratory problems.
AB  - Since Mycoplasma hyopneumoniae isolation in appropriate media is a difficult task
      and impractical for daily routine diagnostics, Nested-PCR (N-PCR) techniques are
      currently used to improve the direct diagnostic sensitivity of Swine Enzootic
      Pneumonia. In a first experiment, this paper describes a N-PCR technique
      optimization based on three variables: different sampling sites, sample transport
      media, and DNA extraction methods, using eight pigs. Based on the optimization
      results, a second experiment was conducted for testing validity using 40 animals.
      In conclusion, the obtained results of the N-PCR optimization and validation
      allow us to recommend this test as a routine monitoring diagnostic method for
      Mycoplasma hyopneumoniae infection in swine herds. 

PMID- 24031249
TI  - Microbiological and histopathological aspects of canine pyometra.
AB  - As pyometra is recognized as one of the main causes of disease and death in the
      bitch the purposes of this study were to evaluate microbiological and
      histopathological aspects of canine pyometra and to research the virulence
      factors of the E. coli isolates identifying possible risks to human health. The
      microbiological isolation from the intrauterine contents of 100 dogs with
      pyometra was carried out and the virulence factors in the E. coli strains were
      identified using PCR method. This study also consisted of the counting of
      microorganisms colonies forming units in samples of intrauterine content, tests
      of antimicrobial susceptibility of the E. coli isolates and the histological
      examination of the uterus. E. coli was the most prevalent microorganism isolated
      (76.6%) and 120 strains (79.5%) were positive for sfa, 86 (56.9%) were positive
      for cnf, 87 (57.6%) were positive for pap, 52 (34.4%) were positive for hly, 51
      (33.8%) were positive for iuc and 5 (3.3%) were positive for afa genes. One
      observed more sensitivity of E. coli to norfloxacin, polimixin B, sulphazotrin,
      chloranfenicol and enrofloxacin. In 42% of the samples of uterine walls where
      microorganisms were isolated, the sizes of the areas of the inflammatory
      responses corresponded to 39-56%. Virulence factors were identified in 98.0% of
      the strains evaluated, demonstrating a high frequency of potentially pathogenic
      E. coli. It must be considered that dogs are animals that are living in close
      proximity to man for thousands of years and have an important role in the
      transmission of E. coli to other animals and to man. 

PMID- 24031250
TI  - Comparison of agglutinating and neutralizing antibodies to serovar hardjo in sows
      immunized with two commercial whole culture polivalent anti-leptospira bacterins.
AB  - It was performed the comparison of the intensity and duration of agglutinating
      and neutralizing antibodies to serovar Hardjo in swines vaccinated with two
      commercial anti-leptospira bacterins. Sows no reactive to 24 Leptospira sp
      serovars in the microscopic agglutination test (MAT) were divided in three
      groups: Group A (n=08): received two vaccine A doses with 30 days interval, Group
      B (n=08) two vaccine B doses with 30 days interval and Group C (n=08): control no
      vaccinated against leptospirosis.Blood samples were collected each 30 days during
      six months following the first vaccination. The sera were tested by MAT and
      growth inhibition test (GIT) to serovar Hardjo in order to evaluate respectively
      agglutinating and neutralizing antibodies. It was found that neutralizing
      antibodies persisted for a longer time than the agglutinating ones and that the
      absence of agglutinating antibodies does not means in the absence of the
      neutralizing. The peaks of agglutinating antibodies was obtained at least 30 days
      earlier than that produced by neutralizing. The duration of both kinds of
      antibodies measured differed between the two bacterines tested. The period for
      inducing neutralizing antibodies against serovar Hardjo indicated that gilts must
      be immunized with two doses of whole culture anti-leptospira bacterines applied
      30 days each other at least 90 days before the first mating. For the maintenance
      of hight levels of neutralizing antibodies the revaccinations must be performed
      every six months after the first vaccination. 

PMID- 24031251
TI  - In vitro isolation and molecular characterization of an Ehrlichia canis strain
      from Sao Paulo, Brazil.
AB  - An Ehrlichia canis isolate was obtained from an naturally infected dog exhibiting
      clinical signs of ehrlichiosis in Sao Paulo Municipality, state of Sao Paulo,
      Brazil. The isolate was characterized by PCR and DNA sequencing of portions of
      the ehrlichial genes dsb, 16SrRNA, and p28. Partial dsb and 16S rRNA sequences
      were identical to three and five other E. canis strains, respectively, from
      different countries and continents (including North America, Africa, Asia and
      Europe). Conversely, the p28 partial sequence for this E. canis (Sao Paulo)
      differed by 1, 2, and 2 nucleotides from the corresponding sequences of the E.
      canis strains Jake (from USA), Oklahoma (USA), and VHE (Venezuela), respectively.
      The results in this study indicate that E. canis is the only recognized Ehrlichia
      species infecting dogs in Brazil. 

PMID- 24031252
TI  - Molecular genetic differentiation of avian Escherichia coli by RAPD-PCR.
AB  - Escherichia coli is one of the most important bacterial avian pathogens and a
      common inhabitant of the gastrointestinal tract of animals. Most pathogenic E.
      coli can not be differentiated biochemically or by classic microbiologic methods.
      Molecular typing methods, particularly PCR, facilitated epidemiological and
      ecological studies of bacteria. Here we describe the application of a random
      amplified polymorphic DNA- polymerase chain reaction (RAPD-PCR) for molecular
      genetic differentiation of E. coli isolates in Iran. In this study 58 E. coli
      isolates including 4 standard strains, 3 food originated isolates, 33 avian
      isolates, 8 isolates form diarrheic calves and 10 isolates from unweaned
      diarrheic lambs were analyzed by RAPD-PCR using primer 1247(5(/)-AAG AGC CCG T
      3(/)). The RAPD analysis showed that these isolates could be grouped into 33 RAPD
      types and avian isolates were discriminated into 29 genotypes. It was shown that
      the primer could not differentiate E. coli isolated from lambs. Discriminatory
      index for entire isolates was 0.912 and for avian isolates was 0.990. We
      concluded that RAPD-PCR can be used as a method for molecular differentiation of
      E. coli isolates. 

PMID- 24031253
TI  - Isolation of extraintestinal pathogenic Escherichia coli from diarrheic dogs and
      their antimicrobial resistance profile.
AB  - From January to December 2006, 92 Escherichia coli isolates from 25 diarrheic
      dogs were analyzed by screening for the presence of adhesin-encoding genes (pap,
      sfa, afa), hemolysin and aerobactin genes. Virulence gene frequencies detected in
      those isolates were: 12% pap, 1% sfa, 10% hemolysin and 6.5% aerobactin. Ten
      isolates were characterized as extraintestinal pathogenic E. coli (ExPEC)
      strains; all showed a multidrug resistance phenotype that may represent a reason
      for concern due the risk of dissemination of antimicrobial resistant genes to the
      microbiota of human beings. 

PMID- 24031254
TI  - Isolation and characterization of Leptospira interrogans from pigs slaughtered in
      Sao Paulo State, Brazil.
AB  - With the aim of isolating Leptospira spp., blood serum, kidney, liver and genital
      tract of 137 female swine (40 sows and 97 gilts) and also urine samples from 22
      sows were collected in a slaughterhouse in the State of Sao Paulo, from April
      2003 to August 2004. Four isolates were obtained from animals that presented
      microagglutination test (MAT) titers >= 100 for the serovar Pomona and one was
      obtained from an animal negative by MAT in which Leptospira was isolated from the
      liver and reproductive tract. The presence of leptospiral DNA was investigated by
      PCR, and positive results were found in kidneys of 11 females, liver of two,
      genital tract of two and urine of one of them. Nephrosis, interstitial multifocal
      nephritis, moderate to severe changing, hyalines cylinders and hemorrhagic
      focuses, hepatic and uterine horns congestion were histological lesions observed
      in higher frequency in animals positive for leptospira. The silver impregnation
      (Warthin Starry) confirmed the presence of spirochetes in renal tubules of four
      females with positive leptospira cultures from kidneys. The serogroup of the five
      isolates was identified as Pomona by cross agglutination with reference
      polyclonal antibodies. Molecular characterization of the isolates was carried out
      by variable-number tandem-repeats analysis. All the isolates revealed a pattern
      distinct from the L. interrogans Pomona type strain, but identical to a
      previously identified pattern from strains isolated in Argentina belonging to
      serovar Pomona. 

PMID- 24031255
TI  - Dermatophytosis caused by Microsporum canis and Microsporum gypseum in free
      living Bradypus variegatus (Schiz, 1825) in the state of Pernambuco, Brazil.
AB  - Three cases of dermatophytosis in free living brown-throated three-toed sloths
      (Bradypus variegatus) in the Zona da Mata, North of Pernambuco State, Brazil,
      were studied. Two animals presented areas of alopecia on the pelvic member and
      thorax and one animal on the pelvic member only. The three animals presented
      scabs. Hair and scabs samples were submitted to microscopical examination after
      treatment with a 30 % KOH and cultivated in Mycosel Agar. The direct examination
      indicated the presence of arthrospores in the hair. Colonies grown after seven
      days of culture were confirmed as Microsporum based on examination of the
      structure of the macroconidia. This is the first observation of dermatophytosis
      caused by Microsporum canis and Microsporum gypseum in free living sloths in the
      State of Pernambuco. 

PMID- 24031256
TI  - An alternative for the preadsorption step in the paratuberculosis serodiagnosis:
      Mycobacterium fortuitum.
AB  - ELISAs for paratuberculosis employ a preadsorption step with Mycobacterium phlei
      to diminish unspecific reactions As M. fortuitum is one of the most frequent
      environmental mycobacteria, the purpose of this pilot study was to evaluate its
      use as an alternative for the preadsorption in ELISAs for paratuberculosis.
      Results suggest that M. fortuitum can be an alternative instead of or associated
      to M. phlei with comparable results (kappa > 0.8) to conventional ELISAs using M.
      phlei as a preadsorption antigen. 

PMID- 24031257
TI  - Behaviour of L. monocytogenes in sliced, vacuum-packed mortadella.
AB  - This study evaluated the growth of naturally occurring L. monocytogenes in
      sliced, vacuum-packed mortadella samples during storage at 5 degrees C until the
      expiration date. Tukey's test indicated that counts of L. monocytogenes on 0, 10,
      20, 30 and 40 days of storage were significantly different (p<0.05), indicating
      growth during shelf life. In three trials, the mean increase was 1.72 log cycles.
      Vacuum packing and storage under refrigeration were not effective in controlling
      the growth of L. monocytogenes in sliced mortadella, indicating that good
      manufacturing practices and implemented HACCP programs are essential to assure
      safety of this product. 

PMID- 24031258
TI  - Persistence of Arcobacter butzleri CCUG 30484 on plastic, stainless steel and
      glass surfaces.
AB  - The persistence of A. butzleri CCUG 30484 on various surfaces under 32% and 64%
      relative humidity suspended in physiological saline or nutrient broth to simulate
      relatively clean or soiled conditions was studied using various isolation
      techniques. Our study revealed that A. butzleri CCUG 30484 cells were able to
      survive for a considerable period of time, even after the droplet of suspending
      medium has been visibly dried. An extended survival on polypropylene coupons at
      both humidity levels was observed, particularly at soiled conditions. 

PMID- 24031259
TI  - Incidence and distribution of filamentous fungi during fermentation, drying and
      storage of coffee (Coffea arabica L.) beans.
AB  - The objective of this work was to isolate and characterize filamentous fungi
      present in different stages of harvest, fermentation, drying and storage of
      coffee beans processed by natural method. The cherries were hand-picked and then
      placed on a cement drying platform where they remained until reached 11% of
      humidity. Microbial counts were found in all samples during fermentation and
      drying of the coffee beans. Counts of fungi in the coffee cherries collected from
      the tree (time 0) were around 1.5 x 10(3) CFU/g. This number increased slowly
      during the fermentation and drying reaching values of 2 x 10(5) CFU/g within 22
      days of processing. Two hundred and sixty three isolates of filamentous fungi
      were identified. The distribution of species during fermentation and drying was
      very varied while there was a predominance of Aspergillus species during storage
      period. The genera found were Pestalotia (4), Paecelomyces (4), Cladosporium
      (26), Fusarium (34), Penicillium (81) and Aspergillus (112) and comprised 38
      different species. 

PMID- 24031260
TI  - Quantitative evaluation of Listeria monocytogenes in fresh and processed surubim
      fish (Pseudoplatystoma sp).
AB  - L. monocytogenes is a foodborne psychrotrophic bacterial pathogen of special
      importance for minimally processed foods. In this work, it was enumerated in
      samples of surubim fish by MPN technique. The population of L. monocytogenes was
      estimated as < 0.012 MPN/cm(2) in fresh and < 0.03 MPN/g in minimally processed
      fish. 

PMID- 24031261
TI  - Quantification and molecular characterization of Salmonella isolated from food
      samples involved in salmonellosis outbreaks in Rio Grande do Sul, Brazil.
AB  - Data concerning the prevalence and populations of Salmonella in foods implicated
      in outbreaks may be important to the development of quantitative microbial risk
      assessments of individual food products. In this sense, the objective of the
      present study was to assess the amount of Salmonella sp. in different foods
      implicated in foodborne outbreaks in Rio Grande do Sul occurred in 2005 and to
      characterize the isolated strains using phenotypic and genotypic methods.
      Nineteen food samples involved in ten foodborne outbreaks occurred in 2005, and
      positive on Salmonella isolation at the Central Laboratory of the Health
      Department of the State of Rio Grande do Sul, were included in this study. Food
      samples were submitted to estimation of Salmonella using the Most Probable Number
      (MPN) technique. Moreover, one confirmed Salmonella colony of each food sample
      was serotyped, characterized by its XbaI-macrorestriction profile, and submitted
      to antimicrobial resistance testing. Foods containing eggs, mayonnaise or chicken
      were contaminated with Salmonella in eight outbreaks. Higher counts (>10(7)
      MPN.g(-1)) of Salmonella were detected mostly in foods containing mayonnaise. The
      isolation of Salmonella from multiple food items in five outbreaks probably
      resulted from the cross-contamination, and the high Salmonella counts detected in
      almost all analyzed samples probably resulted from storing in inadequate
      temperature. All strains were identified as S. Enteritidis, and presented a
      unique macrorestriction profile, demonstrating the predominance of one clonal
      group in foods involved in the salmonellosis outbreaks. A low frequency of
      antimicrobial resistant S. Enteritidis strains was observed and nalidixic acid
      was the only resistance marker detected. 

PMID- 24031262
TI  - Xylanase production with xylan rich lignocellulosic wastes by a local soil
      isolate of Trichoderma viride.
AB  - In the present study, cultural and nutritional conditions for enhanced production
      of xylanase by a local soil isolate of Trichoderma viride, using various
      lignocellulosic substrates in submerged culture fermentation have been optimized.
      Of the lignocellulosics used, maize straw was the best inducer followed by jowar
      straw for xylanase production. The highest activity achieved was between 14 to 17
      days of fermentation. A continuous increase in xylanase production was observed
      with increasing level of lignocellulosics in the medium and highest activity was
      observed with maize straw at 5% level. Xylanase production with higher levels of
      lignocellulosics (3 to 5%) of maize, jowar and barseem was found to be higher as
      compared to that with commercial xylan as carbon source. Sodium nitrate was the
      best nitrogen source among the six sources used. Maximum xylanase production was
      achieved with initial medium pH of 3.5-4.0 and incubation temperature of 25oC.The
      enzyme preparation was effective in bringing about saccharification of different
      lignocellulosics. The xylanase production could be further improved by using
      alkali treated straw as carbon source. 

PMID- 24031263
TI  - Identification of Lactobacillus UFV H2B20 (probiotic strain) using DNA-DNA
      hybridization.
AB  - Sequence analyses of the 16S rDNA gene and DNA-DNA hybridization tests were
      performed for identification of the species of the probiotic Lactobacillus UFV
      H2b20 strain. Using these two tests, we concluded that this strain, originally
      considered Lact. acidophilus, should be classified as Lact. delbrueckii. 

PMID- 24031264
TI  - Highly thermostable and alkaline alpha-amylase from a halotolerant-alkaliphilic
      Bacillus sp. AB68.
AB  - An alkaliphilic and highly thermostable alpha-amylase producing Bacillus sp. was
      isolated from Van soda lake. Enzyme synthesis occurred at temperatures between 25
      degrees C and 40 degrees C. Analysis of the enzyme by SDS-PAGE revealed a single
      band which was estimated to be 66 kDa. The enzyme was active in a broad
      temperature range, between 20 degrees C and 90 degrees C, with an optimum at 50
      degrees C; and maximum activity was at pH 10.5. The enzyme was almost completely
      stable up to 80 degrees C with a remaining activity over 90% after 30 min pre
      incubation. Thermostability was not increased in the presence of Ca(2+). An
      average of 75% and 60 degrees C of remaining activity was observed when the
      enzyme was incubated between pH 5 and 9 for 1 h and for 2 h, respectively. The
      activity of the enzyme was inhibited by SDS and EDTA by 38% and 34%,
      respectively. 

PMID- 24031265
TI  - A new PCR approach for the identification of Fusarium graminearum.
AB  - The main objective of this work was to develop a PCR protocol for the
      identification of Fusarium graminearum, based on a pair of primers targeted to a
      segment of the 3'coding region of the gaoA gene that codes for the enzyme
      galactose oxidase (GO). This region has low homology with the same region of GO
      genes from other fungi. Genomic DNA from 17 strains of Fusarium spp. isolated
      from diseased cereals, from several other Fusarium species, and from other fungi
      genera was analyzed in a PCR assay using this primer set. The 17 strains of
      Fusarium spp. were also analyzed for the GO enzyme production in submerse
      fermentation in a new formulated liquid medium. All strains that were
      morphologically and molecularly identified as F. graminearum were able to secrete
      the enzyme and had a positive result in the used PCR protocol. No DNA fragment
      was amplified using genomic DNA from other Fusarium species and species of other
      fungi genera. The results suggest that the proposed PCR protocol is specific and
      can be considered as a new molecular tool for the identification of F.
      graminearum. In addition, the new formulated medium is a cheap alternative for
      screening for GO screening production by F. graminearum. 

PMID- 24031266
TI  - Submerged culture conditions for the production of mycelial biomass and
      antimicrobial metabolites by Polyporus tricholoma Mont.
AB  - Basidiomycete fungi of the Polyporus genus are a source of secondary metabolites
      which are of medicinal interest as antibacterial compounds. As these substances
      are produced in a small amount by the fungi, the study of the cultivation
      conditions in vitro that could possibly optimize their production seems of major
      importance. The effects of glucose and lactose, pH and agitation on biomass
      concentration and on the specific growth rate caused by the basidiomycete
      Polyporus tricholoma were investigated. The initial pH (4.5, 6.5 and 8.5) was
      autoregulated at pH 5.5, and the agitation increased the mycelial growth and the
      specific growth rate. The high concentration of carbon sources (4%) increased
      biomass production. The lactose concentration and the absence of agitation were
      determinant in the production of antibacterial metabolites. The characterization
      of the antibacterial substance by GC-MS indicated a major compound,
      isodrimenediol, produced by the fungus Polyporus tricholoma with activity against
      Staphylococcus aureus. 

PMID- 24031267
TI  - Antibacterial activity of four mouthrinses containing triclosan against salivary
      Staphylococcus aureus.
AB  - The maximum inhibitory dilution (MID) of triclosan-based mouthwashes against 28
      Staphylococcus aureus strains was evaluated. Dilutions ranging from 1/10 to
      1/655,360 were prepared. Strains were inoculated using a Steers multipoint
      inoculator. The MID was considered as the maximum dilution capable of inhibiting
      microorganism growth. The mouthwashes presented different MIDs. 

PMID- 24031268
TI  - Human papillomavirus infection in women attended at a cervical cancer screening
      service in Natal, Brazil.
AB  - We analyzed cervical specimens of 202 women, aged 15 to 64 years, attended at
      Luis Antonio Hospital, Natal, Brazil, to determine the prevalence of HPV and
      identify the more frequent genotypes and risk factors for HPV infection in women
      attended at a cervical cancer screening service. Two specimens were collected
      from each patient: one for cytological examination and the other to detect HPV
      DNA by PCR, and typing by dot blot hybridization. A total of 54.5% of the sample
      had normal cytology and 45.5% had cytological alterations. HPV was detected in
      24.5% of the cytologically normal women and in 59.8% of those with altered
      cytology. Both single and double HPV infection increased the likelihood of
      cytological alterations. Thirteen types of HPV were identified, most of which
      were high risk. HPV 16 was the most prevalent single-type infection, followed by
      HPV 58. The most frequent double infection was the association between HPV 56 and
      57. The prevalence of HPV in cytologically normal women was greater than that
      reported for countries on all the continents except Africa. The inverse was
      observed in women with cytological alterations. The distribution of HPV types was
      similar to that described for the Americas, with some differences. Multiple
      sexual partners was the only risk factor showing an association with the presence
      of HPV infection. 

PMID- 24031269
TI  - Isolation of Pseudomonas aeruginosa strains from dental office environments and
      units in Barretos, state of Sao Paulo, Brazil, and analysis of their
      susceptibility to antimicrobial drugs.
AB  - A wide variety of opportunistic pathogens has been detected in the tubing
      supplying water to odontological equipment, in special in the biofilm lining of
      these tubes. Among these pathogens, Pseudomonas aeruginosa, one of the leading
      causes of nosocomial infections, is frequently found in water lines supplying
      dental units. In the present work, 160 samples of water, and 200 fomite samples
      from forty dental units were collected in the city of Barretos, State of Sao
      Paulo, Brazil and evaluated between January and July, 2005. Seventy-six P.
      aeruginosa strains, isolated from the dental environment (5 strains) and water
      system (71 strains), were tested for susceptibility to six antimicrobial drugs
      most frequently used against P. aeruginosa infections. Susceptibility to
      ciprofloxacin, followed by meropenem was the predominant profile. The need for
      effective means of reducing the microbial burden within dental unit water lines
      is emphasized, and the risk of exposure and cross-infection in dental practice,
      in special when caused by opportunistic pathogens like P. aeruginosa, are
      highlighted. 

PMID- 24031270
TI  - Genetic diversity and antifungal susceptibility testing of Trichosporon asahii
      isolated of Intensive Care Units patients.
AB  - Trichosporon asahii is an opportunistic pathogen, associated with a high
      mortality rate in immunocompromised patients. In this study, ten isolates,
      recovered from oral cavity and urine of patients in Intensive Care Units (ICU)
      over six months, were identified by classical and molecular methods, typed by
      RAPD and tested in vitro for susceptibility to fluconazole, itraconazole, 5
      flucytosine and amphotericin B. A total agreement between the identification of
      Trichosporon sp by PCR based on sequences of the Internal Transcribed Spacer
      Regions (ITS) and on the sequences of small-subunit (SSU) ribosomal DNA (rDNA)
      was found. Randomly amplified of polymorphic DNA (RAPD), with primers P6 and M13,
      was used to determine the genomic profiles. The dendogram analysis indicated that
      almost all strains showed similarity >0.9 among them and all strains were
      multidrug-resistant. This study brings new results on the identification and
      genotyping of T. asahii isolated from Brazilian ICU patients and information
      about their antifungal drugs susceptibility. 

PMID- 24031271
TI  - Yield of four Agaricus bisporus strains in three compost formulations and
      chemical composition analyses of the mushrooms.
AB  - Three compost formulations, consisting of two varieties of Cynodom dactylon (L.)
      Pers. (Coast-cross and Tyfton) and oat (Avena sativa) straw were tested for the
      cultivation of A. bisporus strains ABI-01/01, ABI-04/02, ABI-05/03, and ABI
      06/04. A completely randomized experimental design in a factorial scheme was
      adopted, with 12 treatments (4 A. bisporus strains * 3 types of compost) and 8
      replicates. Each experimental unit corresponded to one box containing 12 - 12.5
      kg fresh wet compost. The data were submitted to analysis of variance and the
      means were compared by Tukey test. According to the results, productivity of
      mushrooms was influenced by strain and/or compost type. It was also verified that
      crude protein, ash, and crude fiber contents in the mushroom varied with A.
      bisporus strain and straw used in the formulation of the compost. 

PMID- 24031272
TI  - Morphological and cytochemical characterization of spores and gills of Lepista
      sordida (Fungi: Basidiomycota).
AB  - Some ultrastructural and cytochemical aspects of Lepista sordida are described.
      Basidiospores with verruculose and irregular ornamentations were observed through
      scanning electron microscopy. Confocal microscopy indicated that most of them
      exhibited a single large lipid body, no acidic vesicles and nucleus localized in
      the cell periphery. 

PMID- 24031273
TI  - Improvement of xylanase production by Cochliobolus sativus in solid state
      fermentation.
AB  - The xylanase production by Cochliobolus sativus strain Cs6 was improved under
      solid state fermentation (SSF). High xylanase activity (1079 U/g) was obtained
      when wheat straw was used after 8 days of incubation. Combinations of sodium
      nitrate with peptone or yeast extract resulted in an increased xylanase
      production (1543 and 1483 U/g, respectively). The Cs6 strain grown in SSF in a
      simple medium, proved to be a promising microorganism for xylanase production. 

PMID- 24031274
TI  - 16S rRNA region based PCR protocol for identification and subtyping of Parvimonas
      micra.
AB  - The present study established a PCR protocol in order to identify Parvimonas
      micra and to evaluate the intra-species diversity by PCR-RFLP of 16S rRNA partial
      sequence. The data indicated that the protocol was able to identify this species
      which could be clustered in five genotypes. 

PMID- 24031275
TI  - Extended-spectrum beta-lactamases producing Klebsiella pneumoniae isolated in two
      hospitals in Goiania/Brazil: detection, prevalence, antimicrobial susceptibility
      and molecular typing.
AB  - This study was developed to evaluate the prevalence of extended-spectrum beta
      lactamases (ESBL) producing Klebsiella pneumoniae in two hospitals (A and B) in
      Goiania, GO, Brazil. The antimicrobial susceptibility of the isolates was
      determined using the MicroScan WalkAway (Dade Behring, USA). Tests to evaluate
      the genetic correlation between the isolates were also performed. For the ESBL
      phenotypic test, the Double-disk diffusion (DD) method was used. The strains
      isolated in Hospital B were submitted to DNA analysis by pulsed-field gel
      electrophoresis (PFGE). The study showed high prevalence of ESBL-producing K.
      pneumoniae (25% in hospital A and 66.7% in hospital B), with high rates of
      antimicrobial resistance. The most active compound was imipenem (100%
      susceptibility in vitro). The PFGE test showed similiarity in five strains and
      variability in six strains.The high prevalence of ESBL-producing Klebsiella may
      be due to individual selection and to dissemination of a common strain. 

PMID- 24031276
TI  - Evaluation of methods for detection and identification of Mycobacterium species
      in patients suspected of having pulmonary tuberculosis.
AB  - Tuberculosis control is a priority for the Ministry of Health policies in Brazil.
      In the present work, the detection of Mycobacterium tuberculosis by the
      Polymerase Chain Reaction (PCR) was standardized, and the laboratory diagnosis of
      pulmonary tuberculosis was evaluated comparing baciloscopy, culture and PCR
      tests. The study was carried out with 117 sputum samples from different patients
      suspected of having pulmonary tuberculosis, for whom physicians had ordered a
      baciloscopy test. Baciloscopy was performed using the Ziehl-Neelsen method, and
      culture was performed by incubation of treated samples in Lowenstein-Jensen's
      medium at 37 degrees C for eight weeks. For PCR, DNA was amplified with a
      specific pair of primers to the M. tuberculosis complex, with a resulting product
      of 123 bp from the insertion element IS6110. Three (2.56%) samples presented a
      positive baciloscopy result and a positive PCR result (100% agreement), and nine
      (7.69%) presented Mycobacterium sp. growth in culture (P= 0.1384). Among six
      samples with positive results in culture, one was identified by PCR-RFLP as
      belonging to the M. tuberculosis complex and one was identified as a non
      tuberculosis mycobacteria. Sensitivity and specificity of PCR compared to culture
      were 33.3% and 100%, respectively. 

PMID- 24031277
TI  - Identification and molecular characterization of norovirus in sao paulo state,
      Brazil.
AB  - Norovirus (NoV), previously called Norwalk-like virus, represents an important
      group of human pathogens associated with outbreaks of nonbacterial
      gastroenteritis. Epidemiological surveys of outbreaks have shown that the most
      important routes of transmission are person-to-person contacts and contaminated
      food and water, with the virus affecting adults and children. NoV is classified
      into genogroups, being genogroups GI, GII and GIV found in humans. In view of the
      high genetic diversity of NoV and the lack of information about this virus in
      Brazil, the aim of the present study was the molecular characterization of NoV
      isolated from diarrheic stool samples of patients from Sao Paulo State. In this
      study, 204 stool specimens collected during diarrhea outbreaks were analyzed by
      RT-PCR, and 12 were sequenced for genogroup confirmation. One-step PCR was
      performed in order to amplify the B region of ORF 1 using the MON 431, 432, 433
      and 434 primer pool. From total, 32 (15.7%) stool specimens were positive for NoV
      genogroup GII. Comparison of the sequences of the PCR products to GenBank
      sequences showed 88.8% to 98.8% identity, suggesting the presence of genogroup
      GII in gastroenteritis outbreaks in Sao Paulo State. 

PMID- 24031278
TI  - Epidemiologically relevant antimicrobial resistance phenotypes in pathogens
      isolated from critically ill patients in a Brazilian Universitary Hospital.
AB  - Antimicrobial resistance is a threat to public health worldwide and is associated
      with higher mortality and morbidity. Despite the extensive knowledge about this
      problem, drug resistance has continued to emerge, especially in intensive care
      units (ICUs). The objective of this study was to evaluate the frequencies of
      epidemiologically relevant resistance phenotypes in pathogens isolated from
      ventilator-associated pneumonia (VAP), bloodstream infections (BSI) and urinary
      tract infections (UTI) in patients admitted in the adult intensive care unit
      (AICU) of the Clinical Hospital of Federal University of Uberlandia, during an
      one year period. Additionally, at the period of the study, the antibiotic
      consumption in AICU was verified. Coagulase-negative staphylococci and S. aureus
      were the main agents of BSI (43.9%), with 60.0% of oxacilin-resistance for both
      microorganisms, Klebsiella-Enterobacter group predominated in UTI (23.4%), with
      resistance to third generation cephalosporins in 58.0% of the isolates; and,
      Pseudomonas aeruginosa in VAP (42.0%), with 72.0% of resistance to imipenem.
      Cephalosporins (49.6%), vancomycin (37.4%) and carbapenems (26.6%) were the most
      prescribed antibiotics in the unit. The comparison of the results with a
      publication of the NNIS program evidenced a worse situation in the studied
      hospital, mainly between Gram-negative, that had surpassed the percentile 90%
      elaborated by that system. Based on these results a reconsideration on the
      empirical use of antibiotics and on prevention and control of nosocomial
      infections practices is recommended. 

PMID- 24031279
TI  - Oxacilin-resistant Coagulase-negative staphylococci (CoNS) bacteremia in a
      general hospital at Sao Paulo city, Brasil.
AB  - In the last decades, coagulase-negative staphylococci (CoNS), especially
      Staphylococcus epidermidis have become an important cause of bloodstream
      infections. In addition, rates of methicillin-resistance among CoNS have
      increased substantially, leading to the use of glicopeptides for therapy. The
      objective of this study was to evaluate eleven consecutives clinically relevant
      cases of oxacillin-resistant CoNS bacteremia in a general hospital localized in
      Sao Paulo city, Brazil. Five different species were identified by different
      phenotypic methods, including S. epidermidis (5), S. haemolyticus (3), S. hominis
      (1), S. warneri (1) and S. cohnii subsp urealyticus (1). A variety of Pulsed
      Field Gel Electrophoresis profiles was observed by macrorestriction DNA analysis
      in S. epidermidis isolates, but two of three S. haemolyticus isolates presented
      the same profile. These data indicated the heterogeneity of the CoNS isolates,
      suggesting that horizontal dissemination of these microorganisms in the
      investigated hospital was not frequent. One S. epidermidis and one S.
      haemolyticus isolates were resistant to teicoplanin and susceptible to
      vancomycin. The selective pressure due to the use of teicoplanin in this hospital
      is relevant. 

PMID- 24031280
TI  - Horizontol dissemination of TEM- and SHV-typr beta-lactamase genes-carrying
      resistance plasmids amongst clonical isolates of Enterobacteriaceae.
AB  - The extended-spectrum beta-lactamase (ESBL)-producing bacteria have been isolated
      at increasing frequency worldwide. Expression of ESBL is often associated with
      multidrug resistance and dissemination by resistance plasmids. During a two-month
      period in 2000, 133 clinical isolates of enterobacterial strains were randomly
      collected from outpatients and inpatients at a university hospital in Turkey. The
      ESBL producing strains were determined by double-disk synergy (DDS) testing.
      Twenty ESBL producing strains (15%) including Escherichia coli (n = 9),
      Klebsiella pneumoniae (n = 7), Klebsiella oxytoca (n = 2) and Enterobacter
      aerogenes (n = 2) were detected and further analyzed for their resistance
      transfer features, plasmid profile and nature of the resistance genes. Plasmid
      transfer assays were performed using broth mating techniques. TEM- and SHV- genes
      were analyzed by polymerase chain reaction (PCR) and hybridization using specific
      probes. EcoRI restriction enzyme analyses of R plasmids were used in the
      detection of epidemic plasmids. Fourteen plasmid profiles (A, B1, B2, C1, and C2
      to L) were obtained with EcoRI restriction enzyme analysis. Most of these
      plasmids were detected to carry both TEM- and SHV-derived genes by PCR, and
      confirmed by localizing each gene by hybridization assay. Epidemiological
      evidence indicated that there was an apparent horizontal dissemination of
      conjugative R plasmids among multidrug-resistant enterobacterial genera and
      species in this hospital. 

PMID- 24031281
TI  - Distribution of Hepatitis C virus (HCV) genotypes in seropositive patients in the
      state of Alagoas, Brazil.
AB  - We determined the frequency of hepatitis C virus (HCV) genotypes in anti-HCV
      seropositive patients in the state of Alagoas, Brazil, by means of nested-reverse
      transcription-polymerase chain reaction (RT-nested-PCR) followed by restriction
      fragment length polymorphism (RFLP) of amplified fragments of the 5'NCR. The
      nested-PCR with genotype-specific primers from the core region was carried out
      when detection was not possible by the first approach. Detectable HCV-RNA was
      present in 115 (74.7%) of 154 serum samples. Genotype 1 was the most frequent
      (77.4%), against 20.9% of genotype 3 and 0.8% of genotype 2. Subtype 1b was
      predominant (65.2%), followed by subtypes 1a (8.7%), and 3a (6.1%). Coinfection
      (1a/3a) was detected in 0.8% of the samples. Indeed, there was no significant
      differences in the prevalence of genotype 1 compared to what has been obtained
      from anti-HCV seropositive patients from other locations in Brazil. Here we
      report for the first time the genotype 2 in the state of Alagoas. 

PMID- 24031282
TI  - Detection of oral streptococci in dental biofilm from caries-active and caries
      free children.
AB  - This work correlated the presence of oral streptococci in dental biofilm with
      clinical indexes of caries and oral hygiene in caries-active and caries-free
      children. S. mutans and/or S. sobrinus in the dental biofilm does not indicate a
      direct risk for developing dental caries. 

PMID- 24031283
TI  - Genetic similarity between staphylococcus sp isolated from human and hospital
      settings, and susceptibility to different antimicrobials.
AB  - One hundred and forty-three samples from human hands and hospital beds were
      collected at a teaching hospital in the city of Ribeirao Preto/SP by swabs, and
      placed in BHI broth. Following a 24 h incubation period at 37 degrees C, they
      were seeded on Petri dishes containing Agar "Staphylococcus Medium 110". Colonies
      typical of the genus Staphylococcus were collected and stored at 4 degrees C
      until tested for catalase, mannitol, hemolysis, DNAse and coagulase. Strains were
      analyzed by RAPD-PCR to verify their similarity, and tested for sensitivity to
      ten different antibiotics. From the ninety-two isolated strains, 67 (72,8%) were
      coagulase- negative and 25 (27,2%) coagulase-positive. Similarity analysis showed
      a great heterogeneity among strains, but some presented 100% similarity.
      Resistance to oxacilin was encountered in 39 (42%) of the strains. Two coagulase
      negative strains were resistant to vancomycin, and eleven (12%) were considered
      multiresistant. Measures such as hand disinfection of the staff and hospital beds
      and rationalization of antibiotic use could contribute to decrease pathogen
      transmission and selection pressure, diminishing the frequency and lethality of
      nosocomial infections. 

PMID- 24031284
TI  - Distribution of biotypes and leukotoxic activity of Aggregatibacter
      actinomycetemcomitans isolated from Brazilian patients with chronic
      periodontitis.
AB  - Aggregatibacter actinomycetemcomitans is an important etiologic agent of the
      periodontitis and is associated with extra-oral infections. In this study, the
      detection of the ltxA gene as well as the ltx promoter region from leukotoxic A.
      actinomycetemcomitans isolated from 50 Brazilian patients with periodontitis and
      50 healthy subjects was performed. The leukotoxic activity on HL-60 cells was
      also evaluated. Leukotoxic activity was determined using a trypan blue exclusion
      method. The 530 bp deletion in the promoter region was evaluated by PCR using a
      PRO primer pair. A. actinomycetemcomitans was detected by culture and directly
      from crude subgingival biofilm by PCR using specific primers. By culture, A.
      actinomycetemcomitans was detected in nine (18%) of the periodontal patients and
      one (2%) healthy subject. However, by PCR, this organism was detected in 44% of
      the periodontal patients and in 16% of the healthy subjects. It was verified a
      great discrepancy between PCR detection of the ltx operon promoter directly from
      crude subgingival biofilm and from bacterial DNA. Only one periodontal sample
      harbored highly leukotoxic A. actinomycetemcomitans. Moreover, biotype II was the
      most prevalent and no correlation between biotypes and leukotoxic activity was
      observed. The diversity of leukotoxin expression by A. actinomycetemcomitans
      suggests a role of this toxin in the pathogenesis of periodontal disease and
      other infectious diseases. 

PMID- 24031285
TI  - Low Prevalence of Helicobacter pylori infection evaluated by stool antigen test
      in preschool and school children.
AB  - The study evaluated the prevalence of Helicobacter pylori infection in toddlers
      using the stool antigen test. Helicobacter pylori was detected in 28/113 (13.1%).
      Crowding and age were risk factors significantly associated to the infection. We
      conclude there is a low prevalence of the infection in the studied children. 

PMID- 24031286
TI  - Antifungal suscepitibility profile of candida spp. oral isolates obtained from
      denture wearers.
AB  - Denture stomatitis is an inflammatory condition that occurs in denture wearers
      and is frequently associated with Candida yeasts. Antifungal susceptibility
      profiles have been extensively evaluated for candidiasis patients or
      immunosupressed individuals, but not for healthy Candida carriers. In the present
      study, fluconazole, itraconazole, voriconazole, terbinafine and 5-flucytosin were
      tested against 109 oral Candida spp. isolates. All antifungal agents were
      effective against the samples tested except for terbinafine. This work might
      provide epidemiological information about Candida spp. drug susceptibility in
      oral healthy individuals. 

PMID- 24031287
TI  - Evaluation of the results of Mycobacterium tuberculosis direct test (MTD) and
      Mycobacterial culture in urine samples.
AB  - Tuberculosis remains a public health problem in Turkey. Rapid detection of
      Mycobacterium tuberculosis plays a key role in control of infection. In this
      article, the Gen-Probe Amplified Mycobacterium Tuberculosis Direct Test (MTD) was
      evaluated for detection of M. tuberculosis in urine samples. The performance of
      the MTD was very good and appropriate for routine laboratory diagnosis. 

PMID- 24031288
TI  - Utilization of agroindustrial residues for lipase production by solid-state
      fermentation.
AB  - The aim of this work was to produce lipases by solid-state fermentation (SSF)
      using, as substrate, agroindustrial residue supplemented with by-products from
      corn oil refining process or olive oil. For a group of ten fungi strains selected
      in the first steps, the lipase activity obtained by SSF varied from 7.7 to 58.6
      U/g of dry substrate (gds). Among the evaluated strains, the Aspergillus niger
      mutant 11T53A14 was selected by presenting the best enzymatic production. For the
      fermentation tests, two substrates were also investigated: wheat bran and corn
      cob, both supplemented with olive oil. The best results were obtained with wheat
      bran. Additionally, three industrial by-products from corn oil refining
      (soapstock, stearin and fatty acids) were evaluated as substitutes to the olive
      oil in the function of lipases production inducer. Among them, soapstock and
      stearin were the best inducers, whereas fatty acids presented an inhibitor
      effect. The highest lipase activities using soapstock, stearin and fatty acids
      were 62.7 U/gds, 37.7 U/gds and 4.1 U/gds, respectively. 

PMID- 24031289
TI  - Cyclodextrin glycosyltransferase production by new Bacillus sp. strains isolated
      from brazilian soil.
AB  - Three strains of Bacillus sp. (BACRP, BACNC-1 and BACAR) were isolated from soil
      adhered to cassava husk. CGTase specific activity for the three isolated strains
      was higher when cultivated at 40 degrees C. Potato starch, cassava starch,
      maltodextrin and glucose were used as carbon source and growth temperatures
      varied from 25 to 55 degrees C. The three isolates presented higher CGTase
      specific activity when cultivated with potato starch at 40 degrees C. Isolated
      BACRP and BACAR presented specific activity of 4.0*10(-3) and 2.2*10(-3) U/mg
      prot at pH 7.0, respectively, when cultivated in mediums added with NaCl 2%; at
      pH 10,0 their activities were of 3.4*10(-3) and 3.0*10(-3) U/mg prot,
      respectively, in the same concentration of NaCl. On the other hand, the isolated
      BACNC-1 presented activity specific of 2.4*10(-3) U/mg prot when cultivated at pH
      7.0 added of NaCl 1%, and at pH 10.0 the specific activity was of 3.4*10(-3) U/mg
      prot without NaCl addition. This work also showed the presence of cyclodextrins
      formed during fermentation process and that precipitation with acetone or
      lyophilization followed by dialysis was efficient at removing CDs
      (cyclodextrins), thus, eliminating interference in the activity assays. The
      enzyme produced by the BACAR strain was partially purified and beta-CD was
      liberated as a reaction product. 

PMID- 24031290
TI  - Production of actinomycin-D by the mutant of a new isolate of Streptomyces
      sindenensis.
AB  - An actinomycin-D producing strain was isolated from soil and characterized as
      Streptomyces sindenensis. The culture was subjected to UV irradiation and a
      mutant with 400% higher actinomycin-D production was isolated (400 mg/l(-1) as
      compared to 80 mg/l(-1) produced by the parent). Production medium was optimized
      and antibiotic yield with the mutant was enhanced to 850 mg/l(-1) which is 963%
      higher as compared with the parent. 

PMID- 24031291
TI  - Culture Conditions stimulating high gamma-Linolenic Acid accumulation by
      Spirulina platensis.
AB  - Gamma-linolenic acid (GLA) production by Spirulina platensis under different
      stress-inducing conditions was studied. Submerged culture studies showed that low
      temperature (25 degrees C), strong light intensity (6 klux) and primrose oil
      supplement (0.8%w/v) induced 13.2 mg/g, 14.6 mg/g and 13.5 mg linolenic acid per
      gram dry cell weight respectively. A careful observation of fatty acid profile of
      the cyanobacteria shows that, oleic acid and linoleic acid, in experiments with
      varying growth temperature and oil supplements respectively, helped in
      accumulating excess gamma-linolenic acid. In addition, cultures grown at
      increasing light regimes maintained the gamma-linolenic acid to the total fatty
      acid ratio(GLA/TFA) constant, despite any change in gamma-linolenic acid content
      of the cyanobacteria. 

PMID- 24031292
TI  - Isolation of Mucorales from processed maize (Zea mays L.) and screening for
      protease activity.
AB  - Mucorales were isolated from maize flour, corn meal and cooked cornflakes using
      surface and depth plate methods. Rhizopus oryzae, Circinella muscae, Mucor
      subtilissimus, Mucor hiemalis f. hiemalis, Syncephalastrum racemosum, Rhizopus
      microsporus var. chinensis and Absidia cylindrospora showed protease activity. 

PMID- 24031293
TI  - Identification of an antifungal metabolite produced by a potential biocontrol
      Actinomyces strain A01.
AB  - Actinomyces strain A01 was isolated from soil of a vegetable field in the suburb
      of Beijing, China. According to the morphological, cultural, physiological and
      biochemical characteristics, and 16S rDNA sequence analysis, strain A01 was
      identified as Streptomyces lydicus. In the antimicrobial spectrum test strain A01
      presented a stable and strong inhibitory activity against several plant
      pathogenic fungi such as Fusarium oxysporum, Botrytis cinerea, Monilinia laxa,
      etc. However, no antibacterial activity was found. In pot experiments in
      greenhouse, the development of tomato gray mold was markedly suppressed by
      treatment with the fermentation broth of the strain A01, and the control efficacy
      was higher than those of Pyrimethanil and Polyoxin. A main antifungal compound
      (purity 99.503%) was obtained from the fermentation broth of strain A01 using
      column chromatography and HPLC. The chemical structural analysis with U V, IR,
      MS, and NMR confirmed that the compound produced by the strain A01 is natamycin,
      a polyene antibiotic produced by S. chattanovgensis, S. natalensis, and S.
      gilvosporeus, widely used as a natural biological preservative for food according
      to previous reports. The present study revealed a new producing strain of
      natamycin and its potential application as a biological control agent for fungal
      plant diseases. 

PMID- 24031294
TI  - A new approach to microbial production of gallic acid.
AB  - In a new approach to microbial gallic acid production by Aspergillus fischeri
      MTCC 150, 40gL(-1) of tannic acid was added in two installments during the
      bioconversion phase of the process (25gL(-1) and 15gL(-1) at 32 and 44h
      respectively). The optimum parameters for the bioconversion phase were found to
      be temperature: 35 degrees C, pH: slightly acidic (3.3-3.5), aeration: nil and
      agitation: 250 rpm. A maximum of 71.4% conversion was obtained after 71h
      fermentation with 83.3% product recovery. The yield was 7.35 g of gallic acid per
      g of biomass accumulated and the fermenter productivity was 0.56 g of gallic acid
      produced per liter of medium per hour. 

PMID- 24031295
TI  - Production of 6-pentyl-alpha-pyrone by trichoderma harzianum in solid-state
      fermentation.
AB  - Many Trichoderma species are able to produce 6-pentyl-alpha-pyrone (6-PP), a
      lactone with coconut-like aroma. In the present work, several culture parameters
      were studied to enhance the production of 6-PP by Trichoderma harzianum 4040 in
      solid-state fermentation. Green coir powder added to a nutrient solution was used
      as support material for fermentation. A Plackett-Burman screening technique was
      applied, followed by a fractionary factorial design. The best culture conditions
      within the experimental domain studied were (100 g support)(-1): sucrose, 3 g;
      NaNO3, 0.24 g; (NH4)2SO4, 0.18 g; KH2PO4, 0.1 g; inoculum concentration, 2.2 *
      10(6) spores; moisture level, 55%. The temperature established was 28 degrees C.
      The fermentation under the selected conditions led to a 6-PP production six times
      higher (5.0 mg/g dry matter) than the initial one (0.8 mg/g dry matter) after
      seven days of cultivation. 

PMID- 24031296
TI  - Polyphasic characterization of Gluconacetobacter diazotrophicus isolates obtained
      from different sugarcane varieties.
AB  - A polyphasic approach was applied to characterize 35 G. diazotrophicus isolates
      obtained from sugarcane varieties cultivated in Brazil. The isolates were
      analyzed by phenotypic (use of different carbon sources) and genotypic tests
      (ARDRA and RISA-RFLP techniques). Variability among the isolates was observed in
      relation to the carbon source use preference. Glucose and sucrose were used by
      all isolates in contrast to myo-inositol, galactose and ribose that were not
      metabolized. The results of the analysis showed the presence of two groups
      clustered at 68% of similarity. The genetic distance was higher when RISA-RFLP
      analysis was used. Analysis of 16S rDNA sequences from isolates showed that all
      of them belonged to the G. diazotrophicus species. Neither effect of the plant
      part nor sugarcane variety was observed during the cluster analysis. The observed
      metabolic and genetic variability will be helpful during the strain selection
      studies for sugarcane inoculation in association with sugarcane breeding
      programs. 

PMID- 24031297
TI  - Kinetics of high-Level of beta-glucosidase production by a 2-deoxyglucose
      resistant mutant of Humicola lanuginosa in submerged fermentation.
AB  - A 2-deoxyglucose-resistant mutant (M7) of Humicola lanuginosa was obtained by
      exposing conidia to gamma-rays and permitting expression in broth containing 0.6%
      2-deoxyglucose (DG) and cellobiose (1%) before plating on DG esculin-ferric
      ammonium citrate agar medium from which colonies showing faster and bigger
      blackening zones were selected. Kinetic parameters for enhanced beta-glucosidase
      (BGL) synthesis by M7 were achieved when corncobs acted as the carbon source. The
      combination between corncobs and corn steep liquor was the best to support higher
      values of all product formation kinetic parameters. Effect of temperature on the
      kinetic and thermodynamic attributes of BGL production equilibrium in the wild
      organism and M7 was studied using batch process at eight different temperatures
      in shake-flask studies. The best performance was found at 45 degrees C and 20 g
      L(-1) corncobs in 64 h. Both growth and product formation (17.93 U mL(-1)) were
      remarkably high at 45 degrees C and both were coupled under optimum working
      conditions. Product yield of BGL from the mutant M7 (1556.5 U g(-1) dry corncobs)
      was significantly higher than the values reported on all fungal and bacterial
      systems. Mutation had thermo-stabilization influence on the organism and mutant
      required lower activation energy for growth and lower magnitudes of enthalpy and
      entropy for product formation than those demanded by the wild organism, other
      mesophilic and thermo-tolerant organisms. In the inactivation phase, the
      organisms needed lower values of activation energy, enthalpy and entropy for
      product formation equilibrium, confirming thermophilic nature of metabolic
      network possessed by the mutant organism. 

PMID- 24031298
TI  - Efficacy of terbinafine and itraconazole on a experimental model of systemic
      sporotrichosis.
AB  - Itraconazole is currently considered the drug of choice to treat the diverse
      clinical presentation of sporotrichosis. On the other hand terbinafine by virtue
      of its excellent in vitro activity is under comparative evaluation for its
      therapeutic potential for a wide range of fungal infections. In this study, our
      aim was to determine the in vivo efficacy of terbinafine and itraconazole on a
      experimental model of systemic sporotrichosis. 120 rats Wistar received an
      injection of 2*10(3) S. schenckii cells by via the lateral tail vein. After 3
      days the animals were treated with terbinafine (250mg/kg) and itraconazole (100
      mg/kg) and their respective diluents. In our model, terbinafine and itraconazole
      were effective in reducing the number of clinical lesions and positive organ
      cultures. There was statistical difference between the groups treated with the
      antifungals in relation to the control groups (p<0,05) concerning the clinical
      alterations, anatomic-pathological findings and in the positive organ cultures of
      the agent, being that the treated animals resulted in the absence and/or
      reduction of all the evaluated parameters. As for the treatments, terbinafine
      showed similar or higher activity that itraconazole in the evaluation of the
      testicle alteration (p=0,0004), as well as in the positive organ cultures of
      microorganism from the organ (p=0,0142). With these results it is possible to
      conclude that the antifungals studied are effective in the treatment of
      experimental systemic sporotrichosis. 

PMID- 24031299
TI  - Antimicrobial resistance in Campylobacter spp isolated from broiler flocks.
AB  - The aim of this study was to assess the antimicrobial susceptibility of 62
      Campylobacter spp. strains obtained from broiler flocks using the agar diffusion
      method. The Campylobacter spp strains were isolated from 22 flocks aged between 3
      and 5 weeks of life, isolated from cloacae swabs, stools and cecal droppings in
      the farm and from the carcass rinsing in the slaughterhouse. Campylobacter spp
      strains were tested on Mueller-Hilton (MH) agar (27 samples) and MH plus TTC agar
      (35 samples). The antimicrobial susceptibility test revealed a 62.5% resistance
      to at least one drug, especially to enrofloxacin (71%), neomycin (50%),
      lincomycin (50%), tetracycline (43%), penicillin (42%), ceftiofur (33%)
      amoxicillin (27%), spiramycin (20%), ampicillin (18%) and norfloxacin (14%),
      whereas a lower percentage of strains was resistant to erythromycin (10%) and
      doxycycline (10%). All strains were sensitive to gentamicin and lincomycin
      spectinomycin and 80% of them to colistin. These results indicate that it is
      necessary to reduce the use of antimicrobials in veterinary and human medicine. 

PMID- 24031300
TI  - Virulence factors and antimicrobial resistance of escherichia coli isolated from
      urinary tract of swine in southern of Brazil.
AB  - The present study determined the molecular and resistance patterns of E. coli
      isolates from urinary tract of swine in Southern of Brazil. Molecular
      characterization of urinary vesicle samples was performed by PCR detection of
      virulence factors from ETEC, STEC and UPEC. From a total of 82 E. coli isolates,
      34 (38.63%) harbored one or more virulence factors. The frequency of virulence
      factors genes detected by PCR were: pap (10.97%), hlyA (10.97%), iha (9.75%), lt
      (8.53%), sta (7.31%) sfa (6.09%), f4 (4.87%), f5 (4.87%), stb (4.87%), f6 (1.21%)
      and f41 (1.21%). Isolates were resistant to penicillin (95.12%), lincomycin
      (93.9%), erythromycin (92.68%), tetracycline (90.24%), amoxicillin (82.92%),
      ampicillin (74.39%), josamycin (79.26%), norfloxacin (58.53%), enrofloxacin
      (57.31%), gentamicin (39.02%), neomycin (37.8%), apramycin (30.48%), colistine
      (30.48%) and cefalexin (6.09%). A number of 32 (39.02%) E. coli isolates harbored
      plasmids. 

PMID- 24031301
TI  - Isolation of leptospira Serovars Canicola and Copenhageni from cattle urine in
      the state of ParanA, Brazil.
AB  - In 2001, 698 urine samples were randomly collected from cattle at a
      slaughterhouse in the State of Parana, Brazil. Direct examination using dark
      field microscopy was carried out immediately after collection. Five putative
      positive samples were cultured in modified EMJH medium, yielding two positive
      cultures (LO-14 and LO-10). Typing with monoclonal antibodies revealed that the
      two isolates were similar to Canicola (LO-14) and Copenhageni (LO-10).
      Microscopic agglutination test results show that Hardjo is the most common
      serovar in cattle in Brazil. Rats and dogs are the common maintenance hosts of
      serovars Copenhageni and Canicola. The excretion of highly pathogenic serovars
      such as Copenhageni and Canicola by cattle can represent an increasing risk for
      severe leptospirosis is large populations, mainly living in rural areas. 

PMID- 24031302
TI  - Plesiomonas shigelloides and Aeromonadaceae family pathogens isolated from marine
      mammals of Southern and Southeastern Brazilian coast.
AB  - The aquatic environment is the habitat of many microorganisms, including
      Plesiomonas shigelloides and Aeromonas species which are pathogenic to human and
      animals. In the present investigation, we evaluated the occurrence of these
      pathogens from marine mammals beached or accidentally captured by fishing net in
      southeastern (RJ) and southern (RS) coastal Brazilian regions. A total of 198
      swabs from 27 specimens of marine mammals, including 11 different species, were
      collected by DEENSP and GEMARS-CECLIMAR/ UFRGS Institutes and sent to
      LRNCEB/IOC/FIOCRUZ. The samples were enriched in Alkaline Peptone Water (APW)
      added with 1% of sodium chloride (NaCl), APW plus 3% NaCl and incubated at 37
      degrees C for 18-24 hours. Following, samples were streaked onto Pseudomonas
      Aeromonas Selective Agar Base (GSP Agar) and suspected colonies were
      biochemically characterized. The results revealed 114 strains, including ten
      Aeromonas species and P. shigelloides. The main pathogens isolated were A.
      veronii biogroup veronii (19.3%), A. caviae (12.3%), A. hydrophila (9.6%) and P.
      shigelloides (7%). The pathogens were isolated in both coastal and offshore
      marine mammals. These data point the importance of epidemiological surveillance
      and microbiological monitoring and reinforce the need to implement environmental
      protection programs, especially related to endangered cetacean species. 

PMID- 24031303
TI  - Antibacterial activity of plant extracts from Brazil against fish pathogenic
      bacteria.
AB  - The aim of this work was to evaluate the antibacterial activity of Brazilian
      plants extracts against fish pathogenic bacteria. Forty six methanolic extracts
      were screened to identify their antibacterial properties against Streptococcus
      agalactiae, Flavobacterium columnare and Aeromonas hydrophila. Thirty one
      extracts showed antibacterial activity. 

PMID- 24031304
TI  - A toxic cyanobacterial bloom in an urban coastal lake, Rio Grande do Sul state,
      Southern Brazil.
AB  - Reports of cyanobacterial blooms developing worldwide have considerably
      increased, and, in most cases, the predominant toxins are microcystins. The
      present study reports a cyanobacterial bloom in Lake Violao, Torres, Rio Grande
      do Sul State, in January 2005. Samples collected on January 13, 2005, were
      submitted to taxonomical, toxicological, and chemical studies. The taxonomical
      analysis showed many different species of cyanobacteria, and that Microcystis
      protocystis and Sphaerocavum cf. brasiliense were dominant. Besides these,
      Microcystis panniformis, Anabaena oumiana, Cylindrospermopsis raciborskii, and
      Anabaenopsis elenkinii f. circularis were also present. The toxicity of the bloom
      was confirmed through intraperitoneal tests in mice, and chemical analyses of
      bloom extracts showed that the major substance was anabaenopeptin F, followed by
      anabaenopeptin B, microcystin-LR, and microcystin-RR. 

PMID- 24031305
TI  - Optimization of nutritional requirements for mycelial growth and sporulation of
      entomogenous fungus Aschersonia aleyrodis Webber.
AB  - The objective of the present study was to investigate the optimal nutritional
      requirements for mycelial growth and sporulation of entomopathogenic fungus
      Aschersonia aleyrodis Webber by orthogonal layout methods. Herein the order of
      effects of nutrient components on mycelial growth was tryptone > Ca(2+) > soluble
      starch > folacin, corresponding to the following optimal concentrations: 1.58%
      Soluble Starch, 3.16% Tryptone, 0.2 mmol l(-1) Ca(2+) and 0.005% Folacin. The
      optimal concentration of each factors for sporulation was 1.16% lactose, 0.394%
      tryptone, 0.4 mmol l(-1) Fe(2+) and 0.00125% VB1, and the effects of medium
      components on sporulation were found to be in the order lactose > VB1 > Fe(2+) >
      tryptone. Under the optimal culture conditions, the maximum production of
      mycelial growth achieved 20.05 g l(-1) after 7 days of fermentation, while the
      maximum spore yield reached 5.23 *10(10) spores l(-1) after 22 days of
      cultivation. This is the first report on optimization of nutritional requirements
      and design of simplified semi-synthetic media for mycelial growth and sporulation
      of A. aleyrodis. 

PMID- 24031306
TI  - Isolation and preliminary characterization of a o-nitrobenzaldehyde-degrading
      Alcaligenes sp. ND1.
AB  - This paper reports the isolation and characterization of a new o
      nitrobenzaldehyde (ONBA)-degrading bacterium, Alcaligenes sp. ND1. ND1 degraded
      almost all ONBA (100 mg L(-1)) in M9 medium within 36 hours. The key enzyme(s)
      involved in the initial biodegradation was a constitutively intracellular
      enzyme(s). This bacterium has great potential utility for bioremediation. 

PMID- 24031307
TI  - Application of a bacterial extracellular polymeric substance in heavy metal
      adsorption in a co-contaminated aqueous system.
AB  - The application of a bacterial extracellular polymeric substance (EPS) in the
      bioremediation of heavy metals (Cd, Zn and Cu) by a microbial consortium in a
      hydrocarbon co-contaminated aqueous system was studied. At the low concentrations
      used in this work (1.00 ppm of each metal), it was not observed an inhibitory
      effect on the cellular growing. In the other hand, the application of the EPS
      lead to a lower concentration of the free heavy metals in solution, once a great
      part of them is adsorbed in the polymeric matrix (87.12% of Cd; 19.82% of Zn; and
      37.64% of Cu), when compared to what is adsorbed or internalized by biomass
      (5.35% of Cd; 47.35% of Zn; and 24.93% of Cu). It was noted an increase of 24% in
      the consumption of ethylbenzene, among the gasoline components that were
      quantified, in the small interval of time evaluated (30 hours). Our results
      suggest that, if the experiments were conducted in a larger interval of time, it
      would possibly be noted a higher effect in the degradation of gasoline compounds.
      Still, considering the low concentrations that were evaluated, it is possible
      that a real system could be bioremediated by natural attenuation process,
      demonstrated by the low effect of those levels of contaminants and co
      contaminants over the naturally present microbial consortium. 

PMID- 24031308
TI  - Effect of gamma radiation on the inactivation of aflatoxin B1 in food and feed
      crops.
AB  - Samples of food crops (peanut, peeled pistachio, unpeeled pistachio, rice, and
      corn) and feed (barley, bran, corn) were autoclave-sterilized, and inoculated
      with 10(6) of spore suspension of an isolate of Aspergillus flavus fungus known
      to produce aflatoxin B1 (AFB1) . Following a 10-day period of incubation at 27 C
      to allow for fungal growth, food and feed samples were irradiated with gamma
      radiation at the doses 4, 6, and 10 kGy. Results indicated that degradation of
      AFB1 was positively correlated with the increase in the applied dose of gamma ray
      for each tested sample. At a dose of 10 kGy percentages of AFB1 degradation
      reached highest values at 58.6, 68.8, 84.6, 81.1 and 87.8% for peanuts, peeled
      pistachios, unpeeled pistachios, corn and rice samples, respectively. In feed
      samples percentages of AFB1 degradation were 45, 66, and 90% in barley, 47, 75,
      and 86% in bran, and 31, 72, and 84% in corn for the doses of 4, 6, and 10 kGy,
      respectively. AFB1 degradation in food samples correlated negatively with oil
      content in irradiated samples. Thus, in peanuts, which contained the highest oil
      content, percentage of AFB1 degradation at 10 kGy was not more than 56.6%,
      whereas, the corresponding value in corn, which contained the lowest oil content,
      reached as high as 80%. The above results indicate the possibility of using gamma
      radiation as a means of degradation of AFB1 in food and feed crops to levels
      lower than the maximum allowed levels. 

PMID- 24031309
TI  - Comparison of methodologies for conidia production by Alternaria alternata from
      citrus.
AB  - Conidia production is a problem in the study of Alternaria alternata from citrus.
      Thus, this study aimed to compare existing methodologies for conidial production
      of A. alternata isolated from Ponkan tangerine (2 isolates), Cravo lemon (1
      isolate), Pera orange (2 isolates) and Murcott tangor (1 isolate). The
      methodologies used were conidia production with 12 and 24 hours under white
      fluorescent light, evaluation with 24 and 48 hours after applying fungal mycelium
      stress technique, cold stress followed by injury of mycelium and evaluation with
      24 hours, using healthy vegetable tissue and the use of black fluorescent near
      ultraviolet (NUV) lamp. Satisfactory result was obtained with A. alternata
      isolate from Murcott tangor, with the production of 2.8 * 10(5) conidia mL(-1),
      when fungal mycelium was stressed (Petri dish with 66.66% of fungi growth) and
      subsequently 24 h of growth. The use of white light (24 h) and black fluorescent
      NUV lamp also induced expressive conidia production by one isolate of Ponkan
      tangerine, which produced 17.2 * 10(5) and 10.1 * 10(5)conidia mL(-1) and another
      of Murcott tangor, which produced 13.9 * 10(5) and 10.1 * 10(5) conidia mL(-1),
      respectively. The remaining methodologies analyzed in this study were not able to
      induce conidia production in satisfactory quantity. The use of both mycelium
      stress technique and white light (24 h) and black fluorescent NUV lamp allowed
      the production of enough quantities of conidia to be used in vitro (detection of
      fungitoxic substances) and in vivo (pathogenicity test) assays, respectively. 

PMID- 24031311
TI  - Purification and characterization of an extreme halothermophilic protease from a
      halophilic bacterium Chromohalobacter sp. TVSP101.
AB  - An extreme halophilic bacterium was isolated from solar saltern samples and
      identified based on biochemical tests and 16S r RNA sequencing as
      Chromohalobacter sp. strain TVSP101. The halophilic protease was purified using
      ultrafiltration, ethanol precipitation, hydrophobic interaction column
      chromatography and gel permeation chromatography to 180 fold with 22% yield. The
      molecular mass of the protease determined by SDS PAGE was 66 kDa. The purified
      enzyme was salt dependent for its activity and stability with an optimum of 4.5 M
      NaCl. The optimum temperature for maximum protease activity was 75oC. The
      protease was optimally active at pH 8 and retained more than 80% of its activity
      in the range of pH 7-10. Sucrose and glycine at 10% (w/v) were the most effective
      osmolytes, retained 100% activity in the absence of NaCl. The activity was
      completely inhibited by ZnCl2 (2 mM), 0.1% SDS and PMSF (1mM). The enzyme was not
      inhibited by 1mM of pepstatin, EDTA and PCMB. The protease was active and
      retained 100% it activity in 10% (v/v) DMSO, DMF, ethanol and acetone. 

PMID- 24031312
TI  - Production of fungal chitosan in liquid cultivation using apple pomace as
      substrate.
AB  - In this work, we propose the reuse of apple pomace as a substrate for fungal
      chitosan production by liquid cultivation of Gongronella butleri CCT4274.
      Different concentrations of reducing sugars and sodium nitrate were added to the
      aqueous extract of apple pomace and the best result was obtained with 40 g/L of
      reducing sugars and 2.5 g/L of sodium nitrate. The results indicate the
      possibility of producing 1.19 g/L of chitosan per liter of culture medium after
      72.5 hours of cultivation, representing around 21% of the biomass content. 

PMID- 24031310
TI  - Principles and applications of polymerase chain reaction in medical diagnostic
      fields: a review.
AB  - Recent developments in molecular methods have revolutionized the detection and
      characterization of microorganisms in a broad range of medical diagnostic fields,
      including virology, mycology, parasitology, microbiology and dentistry. Among
      these methods, Polymerase Chain Reaction (PCR) has generated great benefits and
      allowed scientific advancements. PCR is an excellent technique for the rapid
      detection of pathogens, including those difficult to culture. Along with
      conventional PCR techniques, Real-Time PCR has emerged as a technological
      innovation and is playing an ever-increasing role in clinical diagnostics and
      research laboratories. Due to its capacity to generate both qualitative and
      quantitative results, Real-Time PCR is considered a fast and accurate platform.
      The aim of the present literature review is to explore the clinical usefulness
      and potential of both conventional PCR and Real-Time PCR assays in diverse
      medical fields, addressing its main uses and advances. 

PMID- 24031313
TI  - Xenobiotics enhance laccase activity in alkali-tolerant gamma-proteobacterium JB.
AB  - Various genotoxic textile dyes, xenobiotics, substrates (10 uM) and agrochemicals
      (100 ug/ml) were tested for enhancement of alkalophilic laccase activity in gamma
      proteobacterium JB. Neutral Red, Indigo Carmine, Naphthol Base Bordears and
      Sulphast Ruby dyes increased the activity by 3.7, 2.7, 2.6 and 2.3 fold
      respectively. Xenobiotics/substrates like p-toluidine, 8-hydroxyquinoline and
      anthracine increased it by 3.4, 2.8 and 2.3 fold respectively. Atrazine and
      trycyclozole pesticides enhanced the activity by 1.95 and 1.5 fold respectively. 

PMID- 24031314
TI  - Ligninases production by Basidiomycetes strains on lignocellulosic agricultural
      residues and their application in the decolorization of synthetic dyes.
AB  - Wood rotting Basidiomycetes collected in the "Estacao Ecologica do Noroeste
      Paulista", Sao Jose do Rio Preto, Sao Paulo State, Brazil, concerning
      Aphyllophorales order and identified as Coriolopsis byrsina SXS16, Lentinus
      strigellus SXS355, Lentinus sp SXS48, Picnoporus sanguineus SXS 43 and Phellinus
      rimosus SXS47 were tested for ligninases production by solid state fermentation
      (SSF) using wheat bran or rice straw as culture media. C. byrsina produced the
      highest laccase (200 U mL(-1)) and Lentinus sp produced the highest activities of
      manganese peroxidase (MnP) and lignin peroxidase (LiP) (7 and 8 U mL(-1),
      respectively), when cultivated on wheat bran. The effect of N addition on enzyme
      production was studied in medium containing rice straw and the data showed an
      increase of 3 up to 4-fold in the laccase production compared to that obtained in
      SSF on wheat bran. The laccases presented optimum pH at 3.0-3.5 and were stable
      at neutral pH values. Optimum pH for MnP and LiP activities was at 3.5 and
      between 4.5 and 6.0, respectively. All the strains produced laccase with optimum
      activities between 55-60oC while the peroxidases presented maximum activity at
      temperatures of 30 to 55oC. The crude enzymes promoted decolorization of
      chemically different dyes with around 70% of decolorization of RBBR and cybacron
      blue 3GA in 6h of treatment. The data indicated that enzymes from these
      basidiomycetes strains are able to decolorize synthetic dyes. 

PMID- 24031315
TI  - Constitutive and inducible pectinolytic enzymes from Aspergillus flavipes FP-500
      and their modulation by pH and carbon source.
AB  - Growth and enzymes production by Aspergillus flavipes FP-500 were evaluated on
      pectin, polygalacturonic acid, galacturonic acid, arabinose, rhamnose, xylose,
      glycerol and glucose at different initial pH values. We found that the strain
      produced exopectinases, endopectinases and pectin lyases. Exopectinases and
      pectin lyase were found to be produced at basal levels as constitutive enzymes
      and their production was modulated by the available carbon source and pH of
      culture medium and stimulated by the presence of inducer in the culture medium.
      Endo-pectinase was basically inducible and was only produced when pectin was used
      as carbon source. Our results suggest that pectinases in A. flavipes FP-500 are
      produced in a concerted way. The first enzyme to be produced was exopectinase
      followed by Pectin Lyase and Endo-pectinase. 

PMID- 24031316
TI  - Performance of an Anaerobic Baffled Reactor (ABR) in treatment of cassava
      wastewater.
AB  - The performance of an anaerobic baffled reactor (ABR) was evaluated in the
      treatment of cassava wastewater, a pollutant residue. An ABR divided in four
      equal volume compartments (total volume 4L) and operated at 35oC was used in
      cassava wastewater treatment. Feed tank chemical oxygen demand (COD) was varied
      from 2000 to 7000 mg L(-1) and it was evaluated the most appropriated hydraulic
      retention time (HRT) for the best performance on COD removal. The ABR was
      evaluated by analysis of COD (colorimetric method), pH, turbidity, total and
      volatile solids, alkalinity and acidity. Principal component analysis (PCA) was
      carried to better understand data obtained. The system showed buffering ability
      as acidity decreased along compartments while alkalinity and pH values were
      increased. There was particulate material retention and COD removal varied from
      83 to 92% for HRT of 3.5 days. 

PMID- 24031317
TI  - Production of alkaline protease from Cellulosimicrobium cellulans.
AB  - Cellulosimicrobium cellulans is one of the microorganisms that produces a wide
      variety of yeast cell wall-degrading enzymes, beta-1,3-glucanase, protease and
      chitinase. Dried cells of Saccharomyces cerevisiae were used as carbon and
      nitrogen source for cell growth and protease production. The medium components
      KH2PO4, KOH and dried yeast cells showed a significant effect (p<0.05) on the
      factorial fractional design. A second design was prepared using two factors: pH
      and percentage of dried yeast cells. The results showed that the culture medium
      for the maximum production of protease was 0.2 g/l of MgSO4.7H2O, 2.0 g/l of
      (NH4)2SO4 and 8% of dried yeast cells in 0.15M phosphate buffer at pH 8.0. The
      maximum alkaline protease production was 7.0 +/- 0.27 U/ml over the center point.
      Crude protease showed best activity at 50oC and pH 7.0-8.0, and was stable at
      50oC. 

PMID- 24031318
TI  - Screening of different fungi for decolorization of molasses.
AB  - The decolorization of molasses by 17 different fungi in 2 media was studied.
      Trichoderma viride showed the highest decolorization yield (53.5%) when
      cultivated at 30oC for 7 days in Medium 1 which contained the molasses which was
      diluted to 40 g/L in distilled water. The other Trichoderma species and
      Penicillium sp. also gave similar results of 40-45%. Decolorization yield was
      increased by adding peptone and yeast extract to the production medium except
      Penicillium sp. Growth rate was not related to decolorization yet pH value was.
      When the pH decreased below 5.0 after the incubation, the decolorization yield
      increased. Although reducing sugar in culture broth decreased with decreasing
      color intensity, there was no connection between protein utilization and
      decolorizing activity. 

PMID- 24031319
TI  - Glucosyltransferase production by Klebsiella sp. K18 and conversion of sucrose to
      palatinose using immobilized cells.
AB  - The strain Klebsiella sp. K18 produces the enzyme glucosyltransferase and
      catalyses the conversion of sucrose to palatinose, an alternative sugar that
      presents low cariogenicity. Response Surface Methodology was successfully
      employed to determine the optimal concentration of culture medium components.
      Maximum glucosyltransferase production (21.78 U mL(-1)) was achieved using the
      optimized medium composed by sugar cane molasses (80 g L(-1)), bacteriological
      peptone (7 g L(-1)) and yeast extract (20 g L(-1)), after 8 hours of fermentation
      at 28 degrees C. The conversion of sucrose to palatinose was studied utilizing
      immobilized cells in calcium alginate. The effects of the alginate concentration
      (2-4%), cell mass concentration (20-40%) and substrate concentration (25-45%)
      were evaluated and the yield of palatinose was approximately 62.5%. 

PMID- 24031320
TI  - Selection of endophytic fungi from comfrey (Symphytum officinale L.) for in vitro
      biological control of the phytopathogen Sclerotinia sclerotiorum (Lib.).
AB  - Biological control consists of using one organism to attack another that may
      cause economic damage to crops. Integrated Pest Management (IPM) is a very common
      strategy. The white mold produced by Sclerotinia sclerotiorum (Lib.) causes
      considerable damage to bean crops. This fungus is a soil inhabitant, the symptoms
      of which are characterized by water-soaked lesions covered by a white cottony
      fungal growth on the soil surface and/or the host plant. Possible biological
      control agents taken from plants are being investigated as phytopathogen
      inhibitors. These are endophytic microorganisms that inhabit the intercellular
      spaces of vegetal tissues and are often responsible for antimicrobial production.
      The objective of the present study was to select endophytic fungi isolated from
      comfrey (Symphytum officinale L.) leaves with in vitro antagonist potential
      against the phytopathogenic fungus S. sclerotiorum. Twelve isolates of endophytic
      fungi and a pathogenic strain of S. sclerotiorum were used in the challenge
      method. With the aid of this method, four endophytes with the best antagonistic
      activity against S. sclerotiorum were selected. Pathogen growth inhibition zones
      were considered indicative of antibiosis. The percentages of pathogenic mycelia
      growth were measured both with and without the antagonist, resulting in growth
      reductions of 46.7% to 50.0% for S. sclerotiorum. These analyses were performed
      by evaluating the endophytic/pathogenic mycelia growth in mm/day over an eight
      day period of antagonistic tests. 

PMID- 24031321
TI  - Calidion bombacis, a new combination for Uredo bombacis with the record of
      Bombacopsis glabra (Bombacaceae) as a new host from Brazil.
AB  - The new combination Calidion bombacis is proposed for the rust species formerly
      known as Uredo bombacis. This nomenclatural change is based on the examination of
      newly collected material of this fungus from a new host, Bombacopsis glabra from
      Brazil, and reexamination of the isotype. Until now this fungus was only known to
      occur in Asia (China, India and Sri Lanka). Therefore, this is also the first
      record of this fungus from the Neotropics. 

PMID- 24031322
TI  - Spread of Metallo-beta-lactamases: screening reveals the presence of aBLA SPM-1
      gene in hospital sewage in southern Brazil.
AB  - Of 396 Pseudomonas aeruginosa strains isolated from hospital sewage, the blaSPM-1
      gene was confirmed in nine. This is the first report of environmental P.
      aeruginosa strains carrying the blaSPM-1 gene in Brazil. The carbapenem
      resistance, already disseminated among clinical isolates, has been detected among
      environmental isolates. 

PMID- 24031323
TI  - Nitrogen-deficient microalgae are rich in cell-surface mannose: potential
      implications for prey biorecognition by phagotrophic protozoa.
AB  - Flow cytometry was used to quantify the abundance of mannose-linked
      glycoconjugates on microalgae precultured using low- or high-nitrate media.
      Nitrogen-deficient microalgae were richer in cell-surface mannose than nitrogen
      sufficient. Findings are discussed in view of recent research which reveals
      mannose-specific 'feeding receptors' assist prey biorecognition by phagotrophic
      protozoa that ingest microalgae. 

PMID- 24031324
TI  - Yeast communities in two Atlantic rain Forest fragments in Southeast Brazil.
AB  - We studied the yeast communities associated with fruits, mushrooms, tree
      exudates, and flies of the genus Drosophila, in two Atlantic Rain Forest
      fragments in state of Minas Gerais, Brazil. A total of 456 samples were collected
      from Rio Doce State Park and 142 from Ecological Station of Universidade Federal
      de Minas Gerais. From these samples, 608 yeast isolates were obtained, belonging
      to 71 different species. Among the yeasts isolated from Rio Doce State Park, 17
      isolates were recovered from fruits, 12 from mushrooms, 13 from tree exudates,
      and 299 from Drosophila spp. In the Ecological Station of Universidade Federal de
      Minas Gerais, 24 isolates were recovered from fruits and 243 from Drosophila spp.
      Distinct communities of yeast were observed in Drosophila flies, fruits,
      mushrooms and tree exudates. The highest number of yeast species was recovered
      from Drosophila flies suggesting that flies are the natural vectors of these
      microorganisms. 

PMID- 24031325
TI  - Dominance of Paris-type morphology on mycothallus of Lunularia cruciata colonised
      by Glomus proliferum.
AB  - Microscopic evidence confirms that L. cruciata hosting G. proliferum shows major
      anatomical traits (arbuscules, coils, arbusculate coils and vesicles) generally
      associated arbuscular mycorrhizal roots and the anatomical morphology of intra
      thalli mycelium is predominantly of the Paris-type. Colonised L. cruciata showed
      a reduction of biomass when compared with axenic plants suggesting a drain of
      resources towards the fungus and depletion of nutrients required for optimum
      plant growth. The behaviour of mycothalli regarding available KH2PO4 indicates
      that the nutritional stress threshold for phosphorus (P) is above the residual
      amount of P already present in Phytagel(TM) and in plant inoculum. These raise
      the possibility that in certain circumstances the relationship between L.
      cruciata and G. proliferum be parasitic rather than symbiotic and open the door
      for future studies to ascertain the nature of liverwort-AM fungi relationships. 

PMID- 24031326
TI  - Longitudinal study on occurrence of adenoviruses and hepatitis A virus in raw
      domestic sewage in the city of Limeira, SAo Paulo.
AB  - The aim of this study was to verify the presence and annual distribution of
      adenoviruses and hepatitis A virus in domestic sewage in the city of Limeira, Sao
      Paulo. Fifty samples with a volume of 8 liters each were collected weekly from
      December 2004 to December 2005. The viruses were concentrated by filtration
      through positively charged ZP60S filter membranes, followed by
      ultracentrifugation. Human adenoviruses (HAdV) were detected by PCR followed by
      nested-PCR and screening for species F was done by restriction of the PCR product
      with TaqI endonuclease. Virus infectivity assays were performed by inoculation of
      concentrates onto HEp-2 cell monolayers. RT-PCR was used for the detection of
      hepatitis A virus. HAdV were detected in all samples, and 64% of samples were
      positive for infectious virus. Species F was present in 82% of the samples.
      Hepatitis A virus was detected in 48% of the samples. These results demonstrate
      that HAdV and HAV were present in the domestic sewage of Limeira throughout the
      period of study, demonstrating the importance of an adequate treatment before the
      disposal in the environment. 

PMID- 24031327
TI  - Killer yeasts inhibit the growth of the phytopathogen Moniliophthora perniciosa,
      the causal agent of Witches' Broom disease.
AB  - Fruit and soil yeasts isolated from the Amazon, Atlantic Rainforests and an
      organic farm were screened for killer activity against yeasts. Killer yeasts were
      then tested against the phytopathogen Moniliophthora perniciosa (syn. Crinipellis
      perniciosa) and a Dipodascus capitatus strain and a Candida sp strain inhibited
      its growth. 

PMID- 24031328
TI  - Occurrence and diversity of arbuscular mycorrhizal fungi in trap cultures from
      soils under different land use systems in the Amazon, Brazil.
AB  - The aim of this work was to evaluate the occurrence of arbuscular mycorrhizal
      fungi (AMF) species diversity in soil samples from the Amazon region under
      distinct land use systems (Forest, Old Secondary Forest, Young Secondary Forest,
      Agroforestry systems, Crops and Pasture) using two distinct trap cultures. Traps
      established using Sorghum sudanense and Vigna unguiculata (at Universidade
      Regional de Blumenau -FURB) and Brachiaria decumbens and Neonotonia wightii (at
      Universidade Federal de Lavras - UFLA) were grown for 150 days in greenhouse
      conditions, when spore density and species identification were evaluated. A great
      variation on species richness was detected in several samples, regardless of the
      land use systems from where samples were obtained. A total number of 24 AMF
      species were recovered using both methods of trap cultures, with FURB's traps
      yielding higher number of species. Acaulospora delicata, A. foveata,
      Entrophospora colombiana and two undescribed Glomus species were the most
      abundant and frequent species recovered from the traps. Number of species
      decreased in each genus according to this order: Acaulospora, Glomus,
      Entrophospora, Gigaspora, Archaeospora, Scutellospora and Paraglomus. Spore
      numbers were higher in Young Secondary Forest and Pastures. Our study
      demonstrated that AMF have a widespread occurrence in all land use systems in
      Amazon and they sporulate more abundantly in trap cultures from land uses under
      interference than in the pristine Forest ecosystem. 

PMID- 24031329
TI  - New approach for papaya latex storage without virus degradation.
AB  - Papaya meleira virus (PMeV) is the causal agent of papaya (Carica papaya L.)
      sticky disease, which has been detected through analysis of its double-stranded
      RNA (dsRNA) genome from plant latex. In this work we demonstrate that PMeV dsRNA
      is protected during 25 days when latex is diluted in citrate buffer pH 5.0 (1:1
      v/v) and maintained at -20oC. At the same temperature, some protection was
      observed for pure latex or latex diluted in ultra-pure water. Conversely, the
      dsRNA was almost completely degraded after 25 days when maintained at 25oC,
      indicating the need for freezing. The proper procedures to collect and store
      papaya latex described here will contribute to efficient and large scale use of
      molecular diagnosis of PMeV. 

PMID- 24031330
TI  - Antimicrobial resistance profile of Enterococcus spp isolated from food in
      Southern Brazil.
AB  - Fifty-six Enterococcus spp. strains were isolated from foods in Southern Brazil,
      confirmed by PCR and classified as Enterococcus faecalis (27), Enterococcus
      faecium (23) and Enterococcus spp (6). Antimicrobial susceptibility tests showed
      resistance phenotypes to a range of antibiotics widely administrated in humans
      such as gentamycin, streptomycin, ampicillin and vancomycin. 

PMID- 24031331
TI  - Viability of Staphylococcus xylosus isolated from artisanal sausages for
      application as starter cultures in meat products.
AB  - Viability of Staphylococcus xylosus isolated from artisanal sausages for
      application as starter cultures in meat products Viability of Staphylococcus
      xylosus strains AD1 and U5 isolated from natural fermented sausages was
      investigated as starter cultures in fermented sausages produced in the South
      Region of Brazil. The study demonstrated that the Staphylococcus xylosus strains
      AD1 and U5 showed significant growth during fermentation, stability over freeze
      dried process, negative reaction for staphylococcal enterotoxins and viability
      for using as a single-strain culture or associated with lactic acid bacteria for
      production of fermented sausages. 

PMID- 24031332
TI  - Detection of fumonisin producing Fusarium verticillioides in paddy (Oryza sativa
      L.) using polymerase chain reaction (PCR).
AB  - The study reports the occurrence of fumonisin producing Fusarium verticillioides
      in 90 samples of stored paddy (Oryza sativa L.) collected from different
      geographical regions of Karnataka, India. Fumonisin producing F. verticillioides
      was identified based on micromorphological characteristics and PCR using two sets
      of primers. One set of primers was F. verticillioides species specific, which
      selectively amplified the intergenic space region of rDNA. The other set of
      primers was specific to fumonisin producing F. verticillioides. Eight paddy
      samples were positive for F. verticillioides. Eleven isolates obtained from these
      samples were capable of producing fumonisin. 

PMID- 24031333
TI  - Nutritional changes in powdered red pepper upon in vitro infection of Aspergillus
      flavus.
AB  - Quantitative losses in various biochemical constituents like capsaicin,
      carotenes, ascorbic acid, polyphenols, mineral matter, sugars (soluble and
      insoluble), protein and fat were estimated after the successful growth of
      Aspergillus flavus for 30 days on powdered red pepper. The fungal biomass was
      measured by ergosterol content and Aflatoxin B1 by HPLC. Amongst the various
      nutritional constituents evaluated for nutritional losses and changes the highest
      nutritional loss was reported in total carotenoids (88.55%) followed by total
      sugars (85.5%). The protein content of the infected sample increased from 18.01%
      to 23%. The nutritional profile of chilli powder (Capsicum annum var. sannam L.)
      shows highest share of total soluble sugars (32.89%) and fiber content (21.05%),
      followed by protein (18.01%) and fat (13.32%) making it an ideal solid- substrate
      for mould growth. At the end of incubation the fungal biomass was 192. 25 mg /
      100 gram powder, total plate count 17.5 X 10 (4) CFU/g and Aflatoxin B1 content
      was 30.06 MUg / kg. 

PMID- 24031334
TI  - Ocurrence of Staphylococcus aureus and multiplex pcr detection of classic
      enterotoxin genes in cheese and meat products.
AB  - Multiplex PCR was used to investigate the presence of enterotoxins genes (sea,
      seb, sec, sed and see) and femA gene (specific for Staphylococcus aureus) in
      coagulase-positive staphylococci (CPS) isolated from cheese and meat products.
      From 102 CPS isolates, 91 were positive for femA, 10 for sea, 12 for sed and four
      for see. 

PMID- 24031335
TI  - Validation of a predictive model describing growth of Salmonella in enteral
      feeds.
AB  - The growth of Salmonella enterica subs. enterica sorovar Typhimurium at 25oC was
      monitored in industrialized and hospital formulated enteral feeds and the results
      were used to validate the mathematical model of Salmonella growth presented by
      the Pathogen Modeling Program (PMP) 7.0 (USDA-USA). The generation time of
      Salmonella in enteral feeds ranged from 21 to 34.8 min and, the maximum growth
      rate (MUmax) varied from 1.28 to 1.95 h(-1), resulting in a population increase
      from 5 to 6 log10 cycles within 14 to 24 h incubation. Growth was faster in the
      hospital formulated feed containing vegetables and eggs. The growth kinetic's
      parameters as lag phase; MUmax and maximum population density (MPD) were similar
      to those predicted by the PMP 7.0, with exception of lag phase in enteral diet at
      pH 6.3. The results of this study validated the PMP 7.0 model for describe
      Salmonella growth in enteral feeds and demonstrates the appropriateness of use
      such model to determine the pathogen behavior in a wide range of storage
      conditions in this food. 

PMID- 24031336
TI  - Nosocomial infections in human immunodeficiency virus type 1 (HIV-1) infected and
      AIDS patients: major microorganisms and immunological profile.
AB  - Antiretroviral therapy advances have proportioned to AIDS patients a survival
      increase. At the same time, the permanence of the seropositive people in the
      nosocomial environment becomes common not only by the adverse reactions caused by
      this therapy, but also by several opportunistic diseases that take them into and
      out of hospital environment. During the hospital permanence, the patients expose
      their impaired immune system to the nosocomial virulent microorganisms, and
      acquire destructive nosocomial infections that sometimes can be lethal. Among
      several hospital syndromes described, little is known about infections in
      immunocompromised patients and how their immune system is able to determine the
      course of the infection. The objective of this study was to describe the major
      microorganisms involved in the nosocomial infections of HIV-1 seropositive
      patients associated with their immunological status. The survey was carried out
      with the Hospital Infection Control Service records, from University Hospital,
      Londrina, Parana, Southern of Brazil, during the period from July 2003 to July
      2004. From all the cases studied (n=969), 24 patients (2.5%) had AIDS diagnosis
      and a half of them was women with the mean of CD4(+) T cells counts of 158/mm(3).
      The main topography of the infection was pulmonary (50.0%) and the main isolated
      microorganisms were Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia
      coli. A major incidence of infection was observed in patients with CD4(+) T cells
      counts lower than 50/mm(3). The study of the relationship between the impairment
      of the immune system and infectious agents could provide a better healthcare of
      people living with HIV/AIDS and advances into the nosocomial infection control
      systems. 

PMID- 24031337
TI  - Susceptibility testing of Candida albicans isolated from oropharyngeal mucosa of
      HIV(+) patients to fluconazole, amphotericin B and Caspofungin. killing kinetics
      of caspofungin and amphotericin B against fluconazole resistant and susceptible
      isolates.
AB  - A clear understanding of the pharmacodynamic properties of antifungal agents is
      important for the adequate treatment of fungal infections like candidiasis. For
      certain antifungal agents, the determination of Minimal Fungicidal Concentration
      (MFC) and time kill curve could be clinically more relevant than the
      determination of the Minimal Inhibitory Concentration (MIC). In this study, MIC
      and MFC to fluconazole, amphotericin B and caspofungin against C. albicans
      isolates and the killing patterns obtained with caspofungin and amphotericin B
      against susceptible and resistant strains to fluconazole were determined. The
      results of MICs showed that all C. albicans isolates were highly susceptible to
      amphotericin B, but two isolates were fluconazole resistant. The comparative
      analysis between MIC and MFC showed that MFC of fluconazole was fourfold higher
      than MIC in 41.9% of the C. albicans isolates. Same values of MFC and MIC of
      amphotericin B and caspofungin were found for 71% of the isolates. Correlation
      between time kill curves and MFC of amphotericin B and caspofungin against all 4
      isolates tested was observed. The caspofungin killing effect was more evident at
      MFC in 6 hours of incubation than at MIC in this time, suggesting dependence of
      concentration. The similarity of results of time-kill curve and MFC values
      indicate that determination of MFC is an alternative for the detection of the
      fungicidal activity of these drugs. 

PMID- 24031338
TI  - Investigation of an outbreak of Salmonella Typhi in Battalgazi district, Malatya
      Turkey.
AB  - Salmonella Typhi infections are important public health problems for the
      developing countries. In this study we investigated the molecular epidemiology of
      a suspected well-water borne S. Typhi outbreak occurred in a district of Malatya
      Turkey. This outbreak affected 10 patients in two days. Arbitrary primed
      polymerase chain reaction (AP-PCR) based typing showed two clones, one had seven,
      and the other had three strains, supporting outbreak speculation. By adding
      chlorine to wells by local municipal authority, the outbreak ended within a very
      short time (about ten days). 

PMID- 24031339
TI  - Influence of the length of remaining root canal filling and post space
      preparation on the coronal leakage of Enterococcus faecalis.
AB  - This study evaluated the sealing ability of different lengths of remaining root
      canal filling and post space preparation against coronal leakage of Enterococcus
      faecalis. Forty-one roots of maxillary incisors were biomechanically prepared,
      maintaining standardized canal diameter at the middle and coronal thirds. The
      roots were autoclaved and all subsequent steps were undertaken in a laminar flow
      chamber. The canals of 33 roots were obturated with AH Plus sealer and gutta
      percha. The root canal fillings were reduced to 3 predetermined lengths (n=11):
      G1=6 mm, G2=4 mm and G3=2 mm. The remaining roots served as positive and negative
      controls. Bacterial leakage test apparatuses were fabricated with the roots
      attached to Eppendorf tubes keeping 2 mm of apex submerged in BHI in glass
      flasks. The specimens received an E. faecalis inoculum of 1 x 107 cfu/mL every 3
      days and were observed for bacterial leakage daily during 60 days. Data were
      submitted to ANOVA, Tukey's test and Fisher's test. At 60 days, G1 (6 mm) and G2
      (4 mm) presented statistically similar results (p>0.05) (54.4% of specimens with
      bacterial leakage) and both groups differed significantly (p<0.01) from G3 (2
      mm), which presented 100% of specimens with E. faecalis leakage. It may be
      concluded that the shortest endodontic obturation remnant leaked considerably
      more than the other lengths, although none of the tested conditions avoids
      coronal leakage of E. faecalis. 

PMID- 24031340
TI  - Invasive aspergillosis associated with systemic lupus erythematosus and cardiac
      postoperative complication.
AB  - Aspergillus is a ubiquitous fungus which can cause a variety of clinical
      syndromes. This fungus has emerged as agent of systemic infections and has
      therefore gained considerable public health importance. This paper describes two
      cases of invasive aspergillosis caused by A. fumigatus in immuno-suppressed
      patients and underscores the importance of early identification of Aspergillus
      infection associated with systemic lupus erythematosus and cardiac postoperative
      complications. 

PMID- 24031341
TI  - Molecular differentiation between Salmonella enterica subsp enterica serovar
      Pullorum and Salmonella enterica subsp enterica serovar Gallinarum.
AB  - S. Pullorum (SP) and S. Gallinarum (SG) are very similar. They are the agents of
      pullorum disease and fowl typhoid, respectively, and the two diseases are
      responsible for economic losses in poultry production. Although SP and SG are
      difficult to be differentiated in routine laboratory procedures, the ability to
      metabolize ornithine is a biochemical test that may be used to achieve this aim.
      While SP is able to decarboxylate this amino acid, SG is not. However, the
      isolation of strains showing atypical biochemical behavior has made this
      differentiation difficult. One of the genes associated with the metabolization of
      the amino acid ornithine is called speC, and is found in both serovars. The
      analysis of 21 SP and 15 SG strains by means of PCR did not enable the
      differentiation of the two serovars, because fragments produced were identical.
      However, after enzymatic treatment with restriction enzyme Eco RI, the band
      pattern of each serovar showed to be different, even in samples of atypical
      biochemical behavior. This fact enabled the standardization of the technique for
      a quick and safe differentiation of serovars Pullorum and Gallinarum. 

PMID- 24031342
TI  - EMJH medium with 5-fluorouracil and nalidixic acid associated with serial
      dilution technique used to recover Leptospira spp from experimentally
      contaminated bovine semen.
AB  - Bovine semen experimentally contaminated with Leptospira santarosai serovar
      Guaricura was submitted to the modified EMJH medium with 5-fluorouracil (300mg/L)
      and nalidixic acid (20mg/L), named as "selective medium" and using the serial
      dilution technique, in order to evaluate the percentage of recovery of the added
      microorganism. The selective EMJH medium was found with higher percentage of
      recovery of leptospiras and minor losses of samples due to contamination with
      opportunistic microorganisms than the non-selective EMJH medium: 151/376 (40.0%)
      of positive growth; and 38/376 (10.0%) contamination and 58/376 (15%) and 129/376
      (34.0%), respectively. These results were statistically significant (p<0. 0001;
      Fisher). Differences were found when the frequencies of positive leptospires
      recovery have been compared in the serial dilution technique (10(-1) to 10(-4))
      between the selective and non-selective media at different dilution factors. At
      1/10(th) dilution the percentages found were (0%, 0/80) and (38%, 30/80), at
      1/100(th) dilution, (3%, 2/80) and (49%, 39/ 80) and at 1/1,000(th) dilution,
      (25%, 20/80) and (50%, 40/80), respectively. The percentage of recovery of
      leptospires was found to be directly proportional to the dilution used. The
      methodology of the serial dilution technique (setting at least three dilutions)
      and the use of selective EMJH medium have been found to be efficient for the
      isolation of leptospires from the bovine semen samples. 

PMID- 24031343
TI  - Aerobic bacterial microflora of Broad-snouted caiman (Caiman latirostris) oral
      cavity and cloaca, originating from parque Zoologico Arruda Camara, Paraiba,
      Brazil.
AB  - The objective of this study was to isolate and identify the aerobic bacterial
      microflora from the oral cavity mucosa and cloaca's samples, collected from Broad
      snouted caiman (Caiman latirostris), born and bred in captivity at Parque
      Zoologico Arruda Camara, Joao Pessoa, Paraiba, Brazil. The most common bacteria
      were Staphylococcus sp. (14.74%), Corynebacterium sp. (13.68%), Escherichia coli
      (13.68%) and Shigella sp.(11.58%), and the less common were Citrobacter sp.
      (1.05%), Klebsiella pneumoniae (1.05%) and Salmonella sp. (1.05%).This emphasizes
      the importance of these microorganisms' participation in infectious processes
      (sepsis) and injuries caused by crocodilians. 

PMID- 24031344
TI  - Frequency of virulence genes in Escherichia coli strains isolated from piglets
      with diarrhea in the North Parana State, Brazil.
AB  - Identification of Escherichia coli causing porcine postweaning diarrhea requires
      knowledge regarding the prevalent pathotypes within a given region. A total of
      100 Escherichia coli isolates from piglets with diarrhea in Londrina city, Parana
      State, South Brazil, were screened for the presence of genes for F4, F5, F6, F18,
      F41 fimbrial antigens by specific probes and for enterotoxins (STa, STb, LT and
      STx2e) by polymerase chain reaction (PCR). The results showed that 60% of the
      isolates were positive for one or more of the fimbrial antigens and 92% were
      positive at least for one of the virulence factors examined. Virulence factor
      genes detected were F4 (44%), F18 (38%), F5 (30%), F41 (32%), F6 (25%), LTp-I
      (71%), STa (40%), STb (47%) and STx2e (3%). Twenty four patterns of virulence
      factor according to the different virulence genes form were found and the most
      frequent virulence gene pattern was F4, F18, F41, STa, STb and LT. Most of the
      isolates that carried genes for adhesins also harboured genes for toxins. 

PMID- 24031345
TI  - Sequencing and phylogenetic analysis of the infectious bursal disease virus
      isolates from outbreak in layer flocks in the state of Minas Gerais.
AB  - Sequencing and phylogenetic analysis based on the nucleotide sequence of the gene
      encoding VP2 protein was carried out in order to characterize the agent of two
      outbreaks of infectious bursal disease in layer flocks in the state of Minas
      Gerais in 2004. The results indicate the outbreaks could be related to the
      vaccinal virus. 

PMID- 24031346
TI  - Bacteriocins from Lactobacillus plantarum - production, genetic organization and
      mode of action: producao, organizacao genetica e modo de acao.
AB  - Bacteriocins are biologically active proteins or protein complexes that display a
      bactericidal mode of action towards usually closely related species. Numerous
      strains of bacteriocin producing Lactobacillus plantarum have been isolated in
      the last two decades from different ecological niches including meat, fish,
      fruits, vegetables, and milk and cereal products. Several of these plantaricins
      have been characterized and the aminoacid sequence determined. Different aspects
      of the mode of action, fermentation optimization and genetic organization of the
      bacteriocin operon have been studied. However, numerous of bacteriocins produced
      by different Lactobacillus plantarum strains have not been fully characterized.
      In this article, a brief overview of the classification, genetics,
      characterization, including mode of action and production optimization for
      bacteriocins from Lactic Acid Bacteria in general, and where appropriate, with
      focus on bacteriocins produced by Lactobacillus plantarum, is presented. 

PMID- 24031348
TI  - Serum antileptospiral agglutinins in freshwater turtles from Southern Brazil.
AB  - In this study, we observed the presence of antileptospiral agglutinins in
      freshwater turtles of two urban lakes of Pelotas, Southern Brazil. Forty animals
      (29 Trachemys dorbigny and 11 Phrynops hilarii) were captured and studied.
      Attempts to isolate leptospires from blood and urine samples were unsuccessful.
      Serum samples (titer > 100) reactive to pathogenic strains were observed in 11
      animals. These data encourage surveys of pet turtles to evaluate the risk of
      transmission of pathogenic leptospires to humans. 

PMID- 24031347
TI  - CLSI broth microdilution method for testing susceptibility of Malassezia
      pachydermatis to thiabendazole.
AB  - Thiabendazole, classified as antiparasitic and also used as an antifungal drug,
      can be found as otological solution indicated for treatment of parasitic and
      fungal external otitis in small animals. Malassezia pachydermatis is a yeast
      recognized as a normal inhabitant on the skin and mucous membranes of dogs and
      cats. However, it is considered an opportunistic agent that causes external
      otitis and dermatitis in these animals. The aim of this study was to evaluate the
      in vitro effect of thiabendazole against 51 isolates of M. pachydermatis using
      the CLSI Broth Microdilution method that has been adapted for this yeast species
      (NCCLS, 2002). Based on this test, the Minimum Inhibitory Concentrations (MIC) of
      thiabendazol was calculated. Subsequently, the susceptibility of each isolate
      against this antifungal was determined. It was observed that the MIC of
      thiabendazole against M. pachydermatis ranged from 0.03 to > 4 ug/mL. A total of
      13.7% of the isolates were found to be resistant, 47.1% were intermediate and
      39.2% were sensitive to the drug. The rate of resistance of the yeasts against
      thiabendazole was similar to the results previously obtained with other
      antifungals, while the adapted broth microdilution technique used in this study
      proved to be efficient. 

PMID- 24031349
TI  - Identification of Mycobacterium bovis Isolates by a multiplex PCR.
AB  - Isolates from suggestive bovine tuberculosis lesions were tested by a multiplex
      polymerase chain reaction (m-PCR) targeting for RvD1Rv2031c and IS6110 sequences,
      specific for M. bovis and Mycobacterium tuberculosis complex respectively. The m
      PCR successfully identified as M. bovis 88.24% of the isolates. 

PMID- 24031350
TI  - Activation of the alternative complement pathway in canine normal serum by
      Paracoccidioides brasiliensis.
AB  - The dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of
      paracoccidioidomycosis, a human granulomatous disease. Recently the first case of
      natural disease in dogs was reported. The complement system is an important
      effector component of humoral immunity against infectious agents. Therefore, the
      aim of this study was to evaluate the activation of the dog alternative
      complement pathway by P. brasiliensis. Initially, the ability of erythrocytes of
      guinea pig, rabbit, sheep, chicken and swine to activate the dog alternative
      pathway was evaluated. The guinea pig erythrocytes showed the greatest capacity
      to activate dog alternative pathway. The alternative (AH50) hemolytic activity
      was evaluated in 27 serum samples from healthy dogs and the mean values were 87.2
      AH50/ml. No significant differences were observed in relation to sex and age. The
      alternative pathway activation by P. brasiliensis was higher in serum samples
      from adult dogs when compared to puppies and aged dogs (p <= 0.05). This is the
      first report of dog alternative complement pathway activation by P. brasiliensis
      and suggests that it may play a protective role in canine paracoccidioidomycosis.

PMID- 24031351
TI  - Molecular analysis of the rRNA genes of Babesia spp and Ehrlichia canis detected
      in dogs from RibeirAo Preto, Brazil.
AB  - The partial DNA sequences of the 18S rRNA gene of Babesia canis and the 16S rRNA
      gene of Ehrlichia canis detected in dogs from Ribeirao Preto, Brazil, were
      compared to sequences from other strains deposited in GenBank. The E. canis
      strain circulating in Ribeirao Preto is identical to other strains previously
      detected in the region, whereas the subspecies Babesia canis vogeli is the main
      Babesia strain circulating in dogs from Ribeirao Preto. 

PMID- 24031352
TI  - Multidrug efflux systems in Escherichia coli and Enterobacter cloacae obtained
      from wholesome broiler carcasses.
AB  - Members of the Enterobacteriaceae family are present in the intestines of man and
      animals as commensals or are important disease causing agents. Bacteria bearing
      multidrug efflux systems (MDR) are able to survive adverse ecological niches.
      Multiresistant Escherichia coli and Enterobacter cloacae isolates from wholesome
      broiler carcasses were investigated for the presence of MDR. Lowering of Minimal
      Inhibitory Concentration for antimicrobials in the presence of a proton-motive
      force (PMF) uncoupler was tested as a potential display of the MDR phenotype. PCR
      amplification of the genes encoding AcrA and AcrB, components of a MDR system was
      performed. Diversity of each species was ascertained by Pulsed-Field Gel
      Electrophoresis (PFGE) of DNA digested with endonuclease XbaI. For all the
      isolates, except E. coli 1 and E. cloacae 9, lowering of MIC or of the growth
      rate in the presence of antimicrobials was observed, indicating a PMF dependent
      resistance mechanism. Expected products of DNA amplification with acrAB derived
      primers was obtained with all E. coli strains and with two of the five E. cloacae
      strains. Dendrogram generated shows diverse pulsetypes, confirming the genetic
      diversity among the strains. An important issue and related public health is the
      fact that different models and mechanisms of antimicrobial resistance are present
      in a small number of non-pathogenic strains and isolated from the same origin.
      These may be sources of resistance genes to others microorganisms, among them,
      pathogenic strains. 

PMID- 24031353
TI  - Epidemiological aspects of astrovirus and coronavirus in poults in the South
      Eastern Region of Brazil.
AB  - A survey of Turkey Coronavirus (TCoV) and Astrovirus (TAstV-2) prevalence was
      carried out from February to December during 2006 year in semiarid region of
      Brazil, from a turkey producer area, localized in South Eastern of Brazil. To
      asses the risk factor related to clinical material, climatic condition and type
      of RT-PCR applied, cloacal swabs (CS), faeces, sera, bursa of Fabricius (BF),
      thymus (TH) and spleen (SP) and ileum-caeca region were collected from 30-day-old
      poults suffering of enteritis episode characterized as poult enteritis mortality
      syndrome (PEMS). The PEMS clinical features were characterized by watery to foamy
      faeces, light brown-yellow in colour and low mortality rate. Meteorological data
      (rainfall and relative humidity) observed during along the study presented
      monthly average temperature ranging from 39.3 and 31.2oC, precipitation in rainy
      season from 40 to 270.3 mm/month, and no rain during dry season. Simplex RT-PCR
      gave odds ratio (OR) values suggesting that ileum-caeca region is at higher
      chance (OR=1.9; p=0.9741) to have both viral RNA than faeces (OR=1.5; p=0.7319).
      However, multiplex RT-PCR showed 3.98 (p=0.89982) more chance to give positive
      results in faeces than CS at dry season. The major risk factors seem to be low
      rate of humidity and high temperatures at winter, probably responsible for
      spread, easily, the TCoV and TAstv-2 among the flocks. The positive results of
      both virus suggested that they can play an important role in enteric disorders,
      associated to low humidity and high temperatures frequently found in tropical
      countries. 

PMID- 24031354
TI  - Detection of methicillin resistance and slime factor production of Staphylococcus
      aureus in bovine mastitis.
AB  - This study aimed to detect methicillin resistant and slime producing
      Staphylococcus aureus in cases of bovine mastitis. A triplex PCR was optimized
      targetting 16S rRNA, nuc and mecA genes for detection of Staphylococcus species,
      S. aureus and methicillin resistance, respectively. Furthermore, for detection of
      slime producing strains, a PCR assay targetting icaA and icaD genes was
      performed. In this study, 59 strains were detected as S. aureus by both
      conventional tests and PCR, and 13 of them were found to be methicillin resistant
      and 4 (30.7%) were positive for mecA gene. Although 22 of 59 (37.2%) S. aureus
      isolates were slime-producing in Congo Red Agar, in PCR analysis only 15 were
      positive for both icaA and icaD genes. Sixteen and 38 out of 59 strains were
      positive for icaA and icaD gene, respectively. Only 2 of 59 strains were positive
      for both methicillin resistance and slime producing, phenotypically, suggesting
      lack of correlation between methicillin resistance and slime production in these
      isolates. In conclusion, the optimized triplex PCR in this study was useful for
      rapid and reliable detection of methicillin resistant S. aureus. Furthermore,
      only PCR targetting icaA and icaD may not sufficient to detect slime production
      and further studies targetting other ica genes should be conducted for accurate
      evaluation of slime production characters of S. aureus strains. 

PMID- 24031355
TI  - Antimicrobial susceptibility of Clostridium perfringens strains isolated from
      broiler chickens.
AB  - Clostridium perfringens is a normal inhabitant of the intestinal tract of
      chickens as well as a potential pathogen that causes necrotic enteritis and
      colangio hepatitis. The minimum inhibitory concentration (MIC) of seven different
      compounds used for therapy, growth promotion or prevention of coccidiosis was
      determined by agar dilution method for 55 C. perfringens strains isolated from
      the intestines of broiler chickens. All strains showed high susceptibility to
      penicillin, avilamycin, monensin and narasin. Only 7.3% of the strains showed an
      intermediated sensitivity to lincomycin, and 49 (89.1%) were considered
      susceptible. For tetracycline and bacitracin, 41.8% and 47.3% of strains,
      respectively, were considered resistant. 

PMID- 24031356
TI  - Detection of Mycobacterium avium in pet birds.
AB  - The present study is a report on the presence of Mycobacterium avium in four
      birds of the psittaciform order kept as pets. Anatomopathological diagnosis
      showed lesions suggestive of the agent and presence of alcohol-acid resistant
      bacilli (AARB) shown by the Ziehl-Neelsen staining. The identification of
      Mycobacterium avium was performed by means of PRA (PCR Restriction Analysis). DNA
      was directly extracted from tissue of the lesions and blocked in paraffin. The
      role of this agent in pet bird infection is discussed, as well as its zoonotic
      potential. 

PMID- 24031357
TI  - Biochemical and molecular characterization of Bacillus pumilus isolated from
      coastal environment in Cochin, India.
AB  - Bacillus species constitute a diverse group of bacteria widely distributed in
      soil and the aquatic environment. In this study, Bacillus strains isolated from
      the coastal environment of Cochin, India were identified by detailed conventional
      biochemical methods, fatty acid methyl ester (FAME) analysis and partial 16S rDNA
      sequencing. Analysis of the data revealed that Bacillus pumilus was the most
      predominant species in the region under study followed by B. cereus and B.
      sphaericus. The B. pumilus isolates were further characterized by arbitrarily
      primed PCR (AP-PCR), antibiotic sensitivity profiling and PCR screening for known
      toxin genes associated with Bacillus spp. All B. pumilus isolates were
      biochemically identical, exhibited high protease and lipase activity and
      uniformly sensitive to antibiotics tested in this study. One strain of B. pumilus
      harboured cereulide synthetase gene cesB of B. cereus which was indistinguishable
      from rest of the isolates biochemically and by AP-PCR. This study reports, for
      the first time, the presence of the emetic toxin gene cesB in B. pumilus. 

PMID- 24031358
TI  - Genetic diversity of siderophore-producing bacteria of tobacco rhizosphere.
AB  - The genetic diversity of siderophore-producing bacteria of tobacco rhizosphere
      was studied by amplified ribosomal DNA restriction analysis (ARDRA), 16S rRNA
      sequence homology and phylogenetics analysis methods. Studies demonstrated that
      85% of the total 354 isolates produced siderophores in iron limited liquid
      medium. A total of 28 ARDRA patterns were identified among the 299 siderophore
      producing bacterial isolates. The 28 ARDRA patterns represented bacteria of 14
      different genera belonging to six bacterial divisions, namely beta-, gamma-,
      alpha-Proteobacteria, Sphingobacteria, Bacilli, and Actinobacteria. Especially,
      gamma-Proteobacteria consisting of Pseudomonas, Enterobacter, Serratia, Pantoea,
      Erwinia and Stenotrophomonas genus encountered 18 different ARDRA groups. Results
      also showed a greater siderophore-producing bacterial diversity than previous
      researches. For example, Sphingobacterium (isolates G-2-21-1 and G-2-27-2),
      Pseudomonas poae (isolate G-2-1-1), Enterobacter endosymbiont (isolates G-2-10-2
      and N-5-10), Delftia acidovorans (isolate G-1-15), and Achromobacter xylosoxidans
      (isolates N-46-11HH and N-5-20) were reported to be able to produce siderophores
      under low-iron conditions for the first time. Gram-negative isolates were more
      frequently encountered, with more than 95% total frequency. For Gram-positive
      bacteria, the Bacillus and Rhodococcus were the only two genera, with 1.7% total
      frequency. Furthermore, the Pseudomonas and Enterobacter were dominant in this
      environment, with 44.5% and 24.7% total frequency, respectively. It was also
      found that 75 percent of the isolates that had the high percentages of
      siderophore units (% between 40 and 60) belonged to Pseudomonas. Pseudomonas sp.
      G-229-21 screened out in this study may have potential to apply to low-iron soil
      to prevent plant soil-borne fungal pathogen diseases. 

PMID- 24031359
TI  - Isolation and characterization of a novel strain of Stenotrophomonas maltophilia
      possessing various dioxygenases for monocyclic hydrocarbon degradation.
AB  - A Gram-negative bacterium, designated as strain KB2, was isolated from activated
      sludge and was found to utilize different aromatic substrates as sole carbon and
      energy source. On the basis of morphological and physiochemical characteristics
      and 16S rRNA gene sequence analysis, the isolated strain KB2 was identified as
      Stenotrophomonas maltophilia. Strain KB2 is from among different Stenotrophomonas
      maltophilia strains the first one described as exhibiting the activities of three
      types of dioxygenases depending on the structure of the inducer. The cells grown
      on benzoate and catechol showed mainly catechol 1,2-dioxygenase activity. The
      activity of 2,3-dioxygenase was detected after phenol induction. Protocatechuate
      3,4-dioxygenase was found in crude cell extracts of this strain after incubation
      with 4-hydroxybenzoic acid, protocatechuic acid and vanillic acid. Because of
      broad spectrum of dioxygenases' types that Stenotrophomonas maltophilia KB2 can
      exhibit, this strain appears to be very powerful and useful tool in the
      biotreatment of wastewaters and in soil decontamination. 

PMID- 24031360
TI  - PtSRR1, a putative Pisolithus tinctorius symbiosis related receptor gene is
      expressed during the first hours of mycorrhizal interaction with Castanea sativa
      roots.
AB  - PtSRR1 EST was previously identified in the first hours of Pisolithus tinctorius
      and Castanea sativa interaction. QRT-PCR confirmed PtSRR1 early expression and in
      silico preliminary translated peptide analysis indicated a strong probability
      that PtSRR1 be a transmembrane protein. These data stimulate the PtSRR1 gene
      research during ectomycorrhiza formation. 

PMID- 24031361
TI  - Spore production in Paecilomyces lilacinus (Thom.) samson strains on agro
      industrial residues.
AB  - Paecilomyces lilacinus has potential for pests control. We aimed to analyze
      mycelial growth and spore production in P. lilacinus strains in several agro
      industrial residues and commercial media. This study suggests alternative
      nutrient sources for fungi production and that the biotechnological potential of
      agro-industrial refuses could be employed in byproducts development. 

PMID- 24031362
TI  - Analysis of methane biodegradation by Methylosinus trichosporium OB3b.
AB  - The microbial oxidation of methane in the atmosphere is performed by
      methanotrophic bacteria that use methane as a unique source of carbon and energy.
      The objective of this work consisted of the investigation of the best conditions
      of methane biodegradation by methanotrophic bacteria Methylosinus trichosporium
      OB3b that oxidize it to carbon dioxide, and the use of these microorganisms in
      monitoring methods for methane. The results showed that M. trichosporium OB3b was
      capable to degrade methane in a more effective way with an initial microorganism
      concentration of 0.0700 g.L(-1), temperature of 30oC, pH 6.5 and using 1.79 mmol
      of methane. In these same conditions, there was no bacterial growth when 2.69
      mmol of methane was used. The specific rate of microorganism growth, the
      conversion factor, the efficiency and the volumetric productivity, for the
      optimized conditions of biodegradation were, respectively, 0.0324 h(-1), 0.6830
      gcells/gCH4, 73.73% and 2.7732.10(-3) gcells/L.h. The final product of methane
      microbiological degradation, carbon dioxide, was quantified through the use of a
      commercial electrode, and, through this, the grade of methane conversion in
      carbon dioxide was calculated. 

PMID- 24031363
TI  - Fungicide resistance and genetic variability in plant pathogenic strains of
      Guignardia citricarpa.
AB  - Citrus black spot (CBS) is a plant disease of worldwide occurrence, affecting
      crops in Africa, Oceania, and South America. In Brazil, climate provides
      favorable conditions and CBS has spread to the Southeast and South regions. CBS
      is caused by the fungus Guignardia citricarpa (anamorph: Phyllosticta citricarpa)
      and its control is based on the use of fungicides, such as benzimidazoles. In
      South Africa, the disease was kept under control for 10 years with benomyl, until
      cases of resistance to high concentrations of this fungicide were reported from
      all citrus-producing areas. Azoxystrobin (a strobilurin) has been found effective
      in controlling phytopathogens, including CBS, in a wide range of economically
      important crops. The present study investigated in vitro the effects of the
      fungicides benomyl and azoxystrobin on 10 strains of G. citricarpa isolated from
      lesions in citrus plants from Brazil and South Africa. Benomyl at 0.5 MUg/mL
      inhibited mycelial growth in all strains except PC3C, of African origin, which
      exhibited resistance to concentrations of up to 100.0 MUg/mL. The spontaneous
      mutation frequency for resistance to benomyl was 1.25 * 10(-7). Azoxystrobin,
      even at high concentrations, did not inhibit mycelial growth in any of the
      strains, but significantly reduced sporulation rates, by as much as 100%, at a
      concentration of 5.0 MUg/mL. Variations in sensitivity across strains,
      particularly to the strobilurin azoxystrobin, are possibly related to genetic
      variability in G. citricarpa isolates. 

PMID- 24031364
TI  - Characterization of Mycobacterium tuberculosis complex isolated from iranian and
      afghani patients by spoligotyping method.
AB  - Designing newer drugs, vaccines, and diagnostic techniques is dependent on better
      understanding of M. tuberculosis virulence mechanism. In this study the
      prevalence of pcaA gene was determined in M. tuberculosis strains typed by
      spoligotyping. The associated risk factors among patients with different
      nationalities residing in Iran were also determined. The isolated M. tuberculosis
      strains have been characterized by performing susceptibility tests against four
      first-line antituberculosis drugs and were then subjected to spoligotyping
      characterization. PCR was used for detection of pcaA gene and its nucleotide
      sequence was also determined. Spoligotyping of M. tuberculosis strains resulted
      in 140 different patterns. One hundred twenty two (87.1%) of these spoligotype
      isolates were unique and reported for the first time. The remaining18 (12.8%)
      spoligotype patterns were previously reported from other geographical regions of
      the world. Haarlem family was most prevalent than other genotype. Antibiotic
      resistances were higher in those isolated from the Iranian patients. The pcaA
      gene was detected in M. tuberculosis clinical isolates but not in saprophyte
      strains such as M. kansasi. The results showed that, spread of M. tuberculosis
      strains belonging to the Beijing family among Iranian patients has to be
      considered seriously. This study confirmed the widespread existence of pcaA gene
      in almost all the clinical isolates. It is also important to undertake studies to
      identify which factors are the most significant to consider in tuberculosis
      control program. 

PMID- 24031365
TI  - Candidiasis in pediatric patients with cancer interned in a university hospital.
AB  - Fungi are common causes of infection in immunocompromised patients. Candida
      species are frequently involved in these cases. In order to investigate
      candidiasis in pediatric patients with cancer, clinical samples were collected
      from one hundred and twenty two patients interned in the Oswaldo Cruz University
      Hospital in Recife, Brazil. Yeasts were isolated from thirty-four clinical
      samples. The species isolated were: Candida albicans (fourteen isolates), C.
      parapsilosis (nine isolates), C. guilliermondii (two isolates) and C. tropicalis
      (two isolates). We found that candidemia was most frequent in patients with
      malignant hematology and that C. parapsilosis infections caused the highest
      mortality. 

PMID- 24031366
TI  - Candida isolates in tertiary hospitals in northeastern Brazil.
AB  - Candida is an opportunistic pathogen that affects high-risk patients who are
      either immunocompromised or critically ill and is associated with almost 80% of
      all nosocomial fungal infections, representing the major cause of fungemia with
      high mortality rates (40%). Candida albicans is the main cause of candidemia and
      among the non-albicans species C. parapsilosis, C. glabrata and C. tropicalis are
      the most frequent agents. The aim of this study was to evaluate the distribution
      of Candida species in two tertiary hospitals in Recife, Northeastern Brazil. It
      began by surveying all positive Candida cultures processed by the microbiology
      laboratory from September 2003 to September 2006. The cultures, originated from
      various types of biological material (blood, urine, tracheal, catheter and
      others), were processed by Vitec ((r)) system (Biomerieux SA, France). A total of
      1.279 (hospital A: 837; hospital B: 442) sample isolates were positive for
      Candida. The most frequent species in both hospitals were: C. albicans (367), C.
      tropicalis (363), C. parapsilosis (147), C. glabrata (81), C. krusei (30) and C.
      guillermondii (14). The isolates were obtained from 746 hospitalized patients. A
      total of 221 positive hemocultures were detected in 166 different patients in
      both hospitals, and 113 (68.1%) of these patients with positive hemocultures
      presented Candida in other body sites. This study shows that Candida non-albicans
      was the main isolated agent and evidences the importante of C. tropicalis in
      nosocomial fungal infections. 

PMID- 24031367
TI  - High incidence of co-infection with Malaria and Typhoid in febrile HIV infected
      and AIDS patients in Ekpoma, Edo State, Nigeria.
AB  - This survey was designed to determine the prevalence of Plasmodium falciparum and
      Salmonella Typhi among febrile HIV/AIDS patients in Ekpoma. Malaria and typhoid
      risk factors in Ekpoma included occupation, poor health facilities and poor
      sanitation. Malaria and typhoid are highly prevalent among Ekpoma HIV/AIDS
      patients. 

PMID- 24031368
TI  - Antibody responses elicited in mice immunized with Bacillus subtilis vaccine
      strains expressing Stx2B subunit of enterohaemorragic Escherichia coli O157:H7.
AB  - No effective vaccine or immunotherapy is presently available for patients with
      the hemolytic uremic syndrome (HUS) induced by Shiga-like toxin (Stx) produced by
      enterohaemorragic Escherichia coli (EHEC) strains, such as those belonging to the
      O157:H7 serotype. In this work we evaluated the performance of Bacillus subtilis
      strains, a harmless spore former gram-positive bacterium species, as a vaccine
      vehicle for the expression of Stx2B subunit (Stx2B). A recombinant B. subtilis
      vaccine strain expressing Stx2B under the control of a stress inducible promoter
      was delivered to BALB/c mice via oral, nasal or subcutaneous routes using both
      vegetative cells and spores. Mice immunized with vegetative cells by the oral
      route developed low but specific anti-Stx2B serum IgG and fecal IgA responses
      while mice immunized with recombinant spores developed anti-Stx2B responses only
      after administration via the parenteral route. Nonetheless, serum anti-Stx2B
      antibodies raised in mice immunized with the recombinant B. subtilis strain did
      not inhibit the toxic effects of the native toxin, both under in vitro and in
      vivo conditions, suggesting that either the quantity or the quality of the
      induced immune response did not support an effective neutralization of Stx2
      produced by EHEC strains. 

PMID- 24031369
TI  - Carbapenem-resistant Acinetobacter baumannii outbreak at university hospital.
AB  - Nineteen clonally related imipenem-resistant Acinetobacter baumannii isolates
      were recovered from eight intensive care unit patients. All isolates harboured
      bla OXA-51-like beta-lactamase genes and showed the absence of 22 kDa fraction in
      outer membrane porin profile analysis. It suggests a combination of two
      mechanisms as responsible for carbapenem-resistant phenotypes. 

PMID- 24031370
TI  - Lipid formation and gamma-linolenic acid production by Mucor circinelloides and
      Rhizopus sp., grown on vegetable oil.
AB  - The fungi strains were tested in Bioscreen automated system to select the best
      nutritional source. Following, shaking submserse cultures were studied in media
      containing sole carbon or nitrogen source. The growth of these strains improved
      in media containing vegetable oil, with high concentration of lipids. The high
      concentration of gamma-linolenic acid was obtained with M. circinelloides in
      culture containing sesame oil. 

PMID- 24031371
TI  - Screening for ligninolytic enzymes from autochthonous fungi and applications for
      decolorization of Remazole Marine Blue.
AB  - This study presents new and alternative fungal strains for the production of
      ligninolytic enzymes which have great potential to use in industrial and
      biotechnological processes. Thirty autochthonous fungal strains were harvested
      from Bornova-Izmir in Turkiye. In the fresh fruitbody extracts laccase, manganese
      peroxidase and lignin peroxidase activities, which are the principal enzymes
      responsible for ligninocellulose degradation by Basidiomycetes, were screened.
      Spores of some of the basidiomycetes species such as Cortinarius sp., Trametes
      versicolor, Pleurotus ostreatus, Abortiporus biennis, Lyophyllum subglobisporium,
      Ramaria stricta, Ganoderma carnosum, Lactarius delicious ve Lepista nuda were
      isolated and investigated optimum cultivation conditions in submerged
      fermentation for high yields of ligninolytic enzyme production. In addition,
      isolated fungal strains were monitored on agar plates whether having the
      capability of decolorization of a textile dye Remazol Marine Blue. 

PMID- 24031372
TI  - Use of Bacillus pumilus CBMAI 0008 and Paenibacillus sp. CBMAI 868 for colour
      removal from paper mill effluent.
AB  - Bacillus pumilus and Paenibacillus sp. were applied on the paper mill effluent to
      investigate the colour remotion. Inocula were individually applied in effluent at
      pH 7.0, 9.0 and 11.0. The real colour and COD remotion after 48h at pH 9.0 were,
      respectively, 41.87% and 22.08% for B. pumilus treatment and 42.30% and 22.89%
      for Paenibacillus sp. Gel permeation chromatography was used to verify the molar
      masses of compounds in the non-treated and treated effluent, showing a decrease
      in the compounds responsible for the paper mill effluent colour. 

PMID- 24031373
TI  - Purification and characterization of extracellular lipase from a new strain:
      Pseudomonas aeruginosa SRT 9.
AB  - An extra cellular lipase was isolated and purified from the culture broth of
      Pseudomonas aeruginosa SRT 9 to apparent homogeneity using ammonium sulfate
      precipitation followed by chromatographic techniques on phenyl Sepharose CL- 4B
      and Mono Q HR 5/5 column, resulting in a purification factor of 98 fold with
      specific activity of 12307.8 U/mg. The molecular weight of the purified lipase
      was estimated by SDS-PAGE to be 29 kDa with isoelectric point of 4.5. Maximum
      lipase activity was observed in a wide range of temperature and pH values with
      optimum temperature of 55oC and pH 6.9. The lipase preferably acted on
      triacylglycerols of long chain (C14-C16) fatty acids. The lipase was inhibited
      strongly by EDTA suggesting the enzyme might be metalloprotein. SDS and metal
      ions such as Hg(2+), Zn(2+), Cu(2+), Ag(2+) and Fe(2+) decreased the lipase
      activity remarkedly. Its marked stability and activity in organic solvents
      suggest that this lipase is highly suitable as a biotechnological tool with a
      variety of applications including organo synthetic reactions and preparation of
      enantiomerically pure pharmaceuticals. The Km and Vmax value of the purified
      enzyme for triolein hydrolysis were calculated to be 1.11 mmol/L and 0.05
      mmol/L/min respectively. 

PMID- 24031374
TI  - Novel agents for enzymatic and fungal hydrolysis of stevioside.
AB  - A comparative study on the potential of some biological agents to perform the
      hydrolysis of stevioside was carried out, aiming at establishing an alternative
      methodology to achieve the aglycon steviol or its rearranged derivative
      isosteviol, in high yields to be used in the preparation of novel bioactive
      compounds. Hydrolysis reactions were performed by using filamentous fungi
      (Aspergillus niger, Rhizopus stolonifer and Rhizopus arrhizus), a yeast
      (Saccharomyces cerevisiae) and enzymes (pancreatin and lipases PL250 and VFL
      8000). Pancreatin showed the best hydrolytic activity, furnishing isosteviol at
      93.9% of yield, at pH 4.0, using toluene as a co-solvent. Steviol was produced
      using both pancreatin at pH 7.0 (20.2% yield) and A. niger at pH 7 (20.8% yield).

PMID- 24031375
TI  - Evaluation of a lipopeptide biosurfactant from Bacillus natto TK-1 as a potential
      source of anti-adhesive, antimicrobial and antitumor activities.
AB  - A lipopeptide biosurfactant produced by Bacillus natto TK-1 has a strong surface
      activity. The biosurfactant was found to be an anti-adhesive agent against
      several bacterial strains, and also showed a broad spectrum of antimicrobial
      activity. The biosurfactant induced a significant reduction in tumor cells
      viability in a dose-dependent manner. 

PMID- 24031376
TI  - Free radical scavenging and antimicrobial properties of extracts of wild
      mushrooms.
AB  - Antioxidant and antimicrobial potentials of extracts obtained from four wild
      mushrooms, Termitomyces clypeatus (TCE), Termitomyces robustus (TRE), Lentinus
      subnudus (LSE) and Lenzites species (LZE) collected in Nigeria were investigated.
      LSE and LZE displayed good scavenging activity against 2, 2-Diphenyl-1
      Picrylhydrazyl (DPPH) and ferrous ion radicals at concentration of 2 mg/mL.
      However, TRE and TCE exhibited better superoxide anion scavenging effect at 2
      mg/mL. All extracts (TCE, TRE, LSE and LZE) had comparable scavenging effect on
      hydroxyl radicals as butylated Hydroxytoluene (BHT) used as control. Moreover,
      extracts from the wild mushrooms were able to inhibit the growth of all indicator
      organisms at concentrations between 12.5 mg/mL to 100 mg/mL. LSE and LZE,
      however, showed better antimicrobial effect on the indicator organisms. The
      results suggest that extracts obtained from the four wild mushrooms may serve as
      sources of new bioactive compounds with effective antioxidant and antimicrobial
      activity. 

PMID- 24031377
TI  - Combined application of origanum vulgare l. essential oil and acetic acid for
      controlling the growth of staphylococcus aureus in foods.
AB  - This study evaluated the occurrence of an enhancing inhibitory effect of the
      combined application of Origanum vulgare L. essential oil and acetic acid against
      Staphylococcus aureus by the determination of Fractional Inhibitory Concentration
      (FIC) index and kill-time assay in nutrient broth, meat broth and in a food model
      (meat pieces). Acetic acid showed MIC and MFC of 0.6 and 1.25 MUL.mL(-1),
      respectively. For O. vulgare essential oil MIC and MBC were 1.25 and 2.5 MUL.mL(
      1), respectively. FIC indexes of the mixture of essential oil and acetic acid at
      MIC x 1/2 were <= 1.0, showing an additive effect. No synergy was found at kill
      time study. Anti-staphylococcal effect of the antimicrobials alone or in mixture
      (MIC x 1/2) was lower in meat than in nutrient and meat broths. The effective
      combination of essential oils and organic acids could appear as an attractive
      alternative for the food industry, as the doses to inhibit the microbial growth
      in foods can be lowered. 

PMID- 24031378
TI  - Adherence assays and Slime production of Vibrio alginolyticus and Vibrio
      parahaemolyticus.
AB  - In this study we investigated the phenotypic slime production of Vibrio
      alginolyticus and Vibrio parahaemolyticus strains, food-borne pathogens, using a
      Congo red agar plate assay. Furthermore, we studied their ability to adhere to
      abiotic surfaces and Vero cells line. Our results showed that only V.
      alginolyticus ATCC 17749 was a slime-producer developing almost black colonies on
      Congo red agar plate. Adherence to glace tube showed that all V. alginolyticus
      strains were more adherent than V. parahaemolyticus. Only V. alginolyticus ATCC
      17749 was found to be able to form biofilm on polystyrene microplate wells (OD570
      = 0.532). Adherence to Vero cells showed that all tested strains were non
      adherent after 30 min, however after 60 min all the studied strains become
      adherent. The percentage of adherence ranged from1.23% to 4.66%. 

PMID- 24031379
TI  - In vitro establishment and propagation of a Brazilian strain of Anaplasma
      marginale with appendage in IDE8 (Ixodes scapularis) cells.
AB  - A Brazilian isolate of Anaplasma marginale with appendage was successfully
      established and maintained in vitro in a tick cell line (IDE8). Infection was
      confirmed by optical and transmission electron microscopy. In addition, primers
      MSP1aNF2 and MSP1aNR2 amplified products from DNA extracted from infected IDE8
      cells. Comparisons with partial sequences of the msp1alpha gene and the complete
      genome of A. marginale confirmed that the sequences of amplified fragments were
      from the A. marginale genome. This is the first establishment of a Brazilian A.
      marginale isolate in tick cells, representing a new system for biological and
      molecular studies and also a new source of material for diagnosis and development
      of vaccines. 

PMID- 24031380
TI  - Comparative growth of trichoderma strains in different nutritional sources, using
      bioscreen c automated system.
AB  - Trichoderma is one of the fungi genera that produce important metabolites for
      industry. The growth of these organisms is a consequence of the nutritional
      sources used as also of the physical conditions employed to cultivate them. In
      this work, the automated Bioscreen C system was used to evaluate the influence of
      different nutritional sources on the growth of Trichoderma strains (T. hamatum,
      T. harzianum, T. viride, and T. longibrachiatum) isolated from the soil in the
      Jureia-Itatins Ecological Station (JIES), Sao Paulo State - Brazil. The cultures
      were grown in liquid culture media containing different carbon- (2%; w/v) and
      nitrogen (1%; w/v) sources at 28oC, pH 6.5, and agitated at 150 rpm for 72 h. The
      results showed, as expected, that glucose is superior to sucrose as a growth
      stimulating carbon source in the Trichoderma strains studied, while yeast extract
      and tryptone were good growth-stimulating nitrogen sources in the cultivation of
      T. hamatum and T. harzianum. 

PMID- 24031381
TI  - Structural and Functional Analysis of Giant Strong Component of Bacillus
      thuringiensis Metabolic Network.
AB  - The purpose of this work was to study the giant strong component (GSC) of B.
      thuringiensis metabolic network by structural and functional analysis. Based on
      so-called "bow tie" structure, we extracted and studied GSC with its functional
      significance. Global structural properties such as degree distribution and
      average path length were computed and indicated that the GSC is also a small
      world and scale-free network. Furthermore, the GSC was decomposed and functional
      significant for metabolism of these divisions were investigated by comparing to
      KEGG metabolic pathways. 

PMID- 24031383
TI  - Development of a polymerase chain reaction assay for the detection of
      pseudorabies virus in clinical samples.
AB  - Aujeszky's disease, also known as pseudorabies causes severe economic losses in
      swine industry and affects the pig husbandry all over the world. The conventional
      diagnostic procedure is time-consuming and false-negative results may occur in
      submissions from latently infected animals. The development, optimization and
      evaluation of a polymerase chain reaction (PCR) assay are presented for the
      diagnosis of pseudorabies infection. This assay was based on the amplification of
      a highly conserved viral gD gene fragment. PCR products of the expected size were
      obtained from PRV strains. Non-specific reactions were not observed when a
      related herpesvirus, other porcine DNA genome viruses and uninfected cells were
      used to assess PCR. The analytical sensitivity of the test was estimated to be
      1.34 TCID50/ 50 uL. The analysis of tissue homogenate samples from naturally
      infected animals proved the potential usefulness of the method for a rapid
      disease diagnosis from field cases. A rapid, sensitive and specific PCR-based
      diagnostic assay to detect pseudorabies virus in clinical samples is provided. 

PMID- 24031382
TI  - Assessing the diversity of bacterial communities associated with plants.
AB  - Plant-bacteria interactions result from reciprocal recognition between both
      species. These interactions are responsible for essential biological processes in
      plant development and health status. Here, we present a review of the
      methodologies applied to investigate shifts in bacterial communities associated
      with plants. A description of techniques is made from initial isolations to
      culture-independent approaches focusing on quantitative Polymerase Chain Reaction
      in real time (qPCR), Denaturing Gradient Gel Electrophoresis (DGGE), clone
      library construction and analysis, the application of multivariate analyses to
      microbial ecology data and the upcoming high throughput methodologies such as
      microarrays and pyrosequencing. This review supplies information about the
      development of traditional methods and a general overview about the new insights
      into bacterial communities associated with plants. 

PMID- 24031384
TI  - Comparative efficacies of Zataria multiflora essential oil and itraconazole
      against disseminated Candida albicans infection in BALB/c mice.
AB  - Disseminated candidiasis is a serious problem in public health that results from
      the invasion of Candida species, in particular Candida albicans. The aim of this
      study was to compare the efficacies of Zataria multiflora essential oil and
      itraconazole in clearing C. albicans from the visceral organs of BALB/c mice
      suffered from disseminated candidiasis. Zataria multiflora essential oil was
      extracted using Clevenger-type apparatus and analyzed by gas chromatography mass
      spectrometry (GC-MS). For clearance experiment, mice (20-25 g, N=8 per group)
      received essential oil at doses of 30, 48 and 64 mg/kg and itraconazole at dose
      of 200 mg/kg intraperitoneally (IP) 2 days before and after intravenous
      inoculation of 0.5 * 10(6) C. albicans blastospores. The treated animals were
      sacrificed on day 20, and 0.1 g of the tissue homogenates was plated onto
      specific media. In GC-Mass, the main components of the essential oil were
      carvacrol (61.29%) and thymol (25.18%). The results demonstrated that IP
      administration of 64 mg/kg of the essential oil had the highest efficacy in
      reducing C. albicans and produced 39.5, 21.8, 141.5, 174 and 501-fold reductions
      in mean CFUs per 0.1 gram in Candida infections of the liver, spleen, lungs,
      brain and kidneys, respectively, compared to positive control. Itraconazole
      showed significantly more responsiveness than the essential oil at dose of 30
      mg/kg in clearing C. albicans from the kidneys (P<0.02), brain (P<0.02) and
      spleen (P<0.04), and less responsiveness than that of 64 mg/kg in clearing the
      organism from the brain (P<0.01), lungs (P<0.0005) and kidneys (P<0.0005),
      whereas no significant difference was observed between this drug and Z.
      multiflora at dose of 48 mg/kg. These data explain the increased rate of yeast
      clearance and reduced dissemination to the viscera of Z. multiflora treated mice.

PMID- 24031385
TI  - Isolation of rabies virus from the parotid salivary glands of foxes (Pseudalopex
      vetulus) from Paraiba State, Northeastern Brazil.
AB  - To determine the presence of rabies virus in the parotid salivary glands, 12 road
      killed rabies-positive hoary foxes (Pseudoalopex vetulus) were tested by using
      the fluorescent antibody test (FAT) and mouse inoculation test (MIT). All 12
      parotid salivary glands were positive for both tests, although in some cases
      several passages were required. The findings of this study support the importance
      of the hoary fox as rabies reservoir in the sem-iarid region of Paraiba State,
      Northeastern Brazil. 

PMID- 24031386
TI  - Occurrence of Campylobacter jejuni and Campylobacter coli and their biotypes in
      beef and dairy cattle from the south of Chile.
AB  - The prevalence of Campylobacter jejuni and Campylobacter coli and their biotypes
      in beef and dairy cattle from the South of Chile was established. Campylobacter
      were statistically more prevalent among beef cattle (35.9%) than among dairy
      cattle (21.3%), being C. jejuni the species most frequently isolated. 

PMID- 24031387
TI  - Potentially pathogenic mycoplasmas in the external ear canal of clinically normal
      cattle in Southeast Brazil: first report.
AB  - Mycoplasmas were searched in the ear canal flushing of 60 bovine in Brazil. The
      prevalence obtained was 80%. The percentages of typified species were 12.5%, for
      M. alkalenses; 2.1%, M. arginini; 8.35%, M. bovirhinis; 2.1%, M. bovis; 25.0%, M.
      conjunctivae; 14.6%, M. mycoides subsp. mycoides LC and 10.4% M. capricolum. 

PMID- 24031388
TI  - Mannanoligosaccharide agglutination by Salmonella enterica strains isolated from
      carrier pigs.
AB  - Type-1 fimbriae are associated with most Salmonella enterica serovars and are an
      essential factor for host colonization. Mannanoligosaccharides (MOS), a prebiotic
      that is agglutinated by type-1 fimbriae, are proposed for the control of
      enterobacteria colonization and may be an alternative to Salmonella control in
      pigs. The aim of this study was to evaluate the capability of porcine Salmonella
      strains to adhere to MOS in vitro. A total of 108 strains of Salmonella sp.
      isolated from carrier pigs were evaluated for the amplification of fimA and fimH
      genes, agglutination of MOS and hemagglutination. In all tested strains,
      amplicons of expected size were detected for both fimA and fimH gene. In the
      hemagglutination assays, 31 (28.7%) strains presented mannose-sensitive
      agglutination of erythrocytes, indicating that the strains were expressing type-1
      fimbriae. Considering only strains expressing the type-1 fimbriae, 23 (74.2%)
      presented a strong agglutination of MOS, 3 (9.6%) a weak reaction and 5 (16.2%)
      none. The results indicate that Salmonella enterica strains expressing type-1
      fimbriae can agglutinate effectively in vitro to MOS. 

PMID- 24031389
TI  - First detection of canine parvovirus type 2c in Brazil.
AB  - The presence of canine parvovirus type 2 (CPV-2), 2a and 2b has been described in
      Brazil, however, the type 2c had not been reported until now. In the current
      study, seven out of nine samples from dogs with diarrhea were characterized as
      CPV-2c, indicating that this virus is already circulating in the Brazilian canine
      population. 

PMID- 24031390
TI  - Performance of transport and selective media for swine Bordetella bronchiseptica
      recovery and it comparison to polymerase chain reaction detection.
AB  - Three comparative assays were performed seeking to improve the sensitivity of the
      diagnosis of Bordetella bronchiseptica infection analyzing swine nasal swabs. An
      initial assay compared the recovery of B. bronchiseptica from swabs
      simultaneously inoculated with B. bronchiseptica and some interfering bacteria,
      immersed into three transport formulations (Amies with charcoal, trypticase soy
      broth and phosphate buffer according to Soerensen supplemented with 5% of bovine
      fetal serum) and submitted to different temperatures (10 degrees C and 27 degrees
      C) and periods of incubation (24, 72 and 120 hours). A subsequent assay compared
      three selective media (MacConkey agar, modified selective medium G20G and a
      ceftiofur medium) for their recovery capabilities from clinical specimens. One
      last assay compared the polymerase chain reaction to the three selective media.
      In the first assay, the recovery of B. bronchiseptica from transport systems was
      better at 27 degrees C and the three formulations had good performances at this
      temperature, but the collection of qualitative and quantitative analysis
      indicated the advantage of Amies medium for nasal swabs transportation. The
      second assay indicated that MacConkey agar and modified G20G had similar results
      and were superior to the ceftiofur medium. In the final assay, polymerase chain
      reaction presented superior capability of B. bronchiseptica detection to culture
      procedures. 

PMID- 24031391
TI  - Evaluation of DNA extraction protocols for Brucella abortus pcr detection in
      aborted fetuses or calves born from cows experimentally infected with strain
      2308.
AB  - The objective of the present study was to improve the detection of B. abortus by
      PCR in organs of aborted fetuses from infected cows, an important mechanism to
      find infected herds on the eradication phase of the program. So, different DNA
      extraction protocols were compared, focusing the PCR detection of B. abortus in
      clinical samples collected from aborted fetuses or calves born from cows
      challenged with the 2308 B. abortus strain. Therefore, two gold standard groups
      were built based on classical bacteriology, formed from: 32 lungs (17 positives),
      26 spleens (11 positives), 23 livers (8 positives) and 22 bronchial lymph nodes
      (7 positives). All samples were submitted to three DNA extraction protocols,
      followed by the same amplification process with the primers B4 and B5. From the
      accumulated results for organ, the proportion of positives for the lungs was
      higher than the livers (p=0.04) or bronchial lymph nodes (p=0.004) and equal to
      the spleens (p=0.18). From the accumulated results for DNA extraction protocol,
      the proportion of positives for the Boom protocol was bigger than the PK (p<
      0.0001) and GT (p=0.0004). There was no difference between the PK and GT
      protocols (p=0.5). Some positive samples from the classical bacteriology were
      negative to the PCR and vice-versa. Therefore, the best strategy for B. abortus
      detection in the organs of aborted fetuses or calves born from infected cows is
      the use, in parallel, of isolation by classical bacteriology and the PCR, with
      the DNA extraction performed by the Boom protocol. 

PMID- 24031392
TI  - In vitro antimicrobial susceptibility of staphylococci isolated from canine
      pyoderma in Rio de Janeiro, Brazil.
AB  - The study aimed to determine the etiology and antimicrobial resistance of
      staphylococci isolated from canine pyoderma. Samples were obtained from dogs with
      pyoderma and isolates were identified by biochemical reactions and tested for
      susceptibility to 15 antimicrobials. Thirty nine staphylococci isolates were
      obtained, and S. pseudintermedius was the most frequent (47.4%). All isolates
      showed resistance to at least one drug and 77.1% were multiresistant. The most
      effective drug was oxacillin. The study reports the alarming antimicrobial
      resistance of Staphylococcus isolated from canine pyoderma samples. 

PMID- 24031393
TI  - A defective mutant of Salmonella enterica Serovar Gallinarum in cobalamin
      biosynthesis is avirulent in chickens.
AB  - Salmonella enterica serovar Gallinarum (SG) is a fowl typhoid agent in chickens
      and is a severe disease with worldwide economic impact as its mortality may reach
      up to 80%. It is one of a small group of serovars that typically produces typhoid
      like infections in a narrow range of host species and which therefore represents
      a good model for human typhoid. The survival mechanisms are not considered to be
      virulent mechanisms but are essential for the life of the bacterium. Mutants of
      Salmonella Gallinarum containing defective genes, related to cobalamin
      biosynthesis and which Salmonella spp. has to be produced to survive when it is
      in an anaerobic environment, were produced in this study. Salmonella Gallinarum
      is an intracellular parasite. Therefore, this study could provide information
      about whether vitamin B12 biosynthesis might be essential to its survival in the
      host. The results showed that the singular deletion in cbiA or cobS genes did not
      interfere in the life of Salmonella Gallinarum in the host, perhaps because
      single deletion is not enough to impede vitamin B12 biosynthesis. It was noticed
      that diluted SG mutants with single deletion produced higher mortality than the
      wild strain of SG. When double mutation was carried out, the Salmonella
      Gallinarum mutant was unable to provoke mortality in susceptible chickens. This
      work showed that B12 biosynthesis is a very important step in the metabolism of
      Salmonella Gallinarum during the infection of the chickens. Further research on
      bacterium physiology should be carried out to elucidate the events described in
      this research and to assess the mutant as a vaccine strain. 

PMID- 24031394
TI  - Phylogenetic relationships between Bacillus species and related genera inferred
      from 16s rDNA sequences.
AB  - Neighbor-joining, maximum-parsimony, minimum-evolution, maximum-likelihood and
      Bayesian trees constructed based on 16S rDNA sequences of 181 type strains of
      Bacillus species and related taxa manifested nine phylogenetic groups. The
      phylogenetic analysis showed that Bacillus was not a monophyletic group. B.
      subtilis was in Group 1. Group 4, 6 and 8 respectively consisted of thermophiles,
      halophilic or halotolerant bacilli and alkaliphilic bacilli. Group 2, 4 and 8
      consisting of Bacillus species and related genera demonstrated that the current
      taxonomic system did not agree well with the 16S rDNA evolutionary trees. The
      position of Caryophanaceae and Planococcaceae in Group 2 suggested that they
      might be transferred into Bacillaceae, and the heterogeneity of Group 2 implied
      that some Bacillus species in it might belong to several new genera. Group 9 was
      mainly comprised of the genera (excluding Bacillus) of Bacillaceae, so some
      Bacillus species in Group 9: B. salarius, B. qingdaonensis and B. thermcloacae
      might not belong to Bacillus. Four Bacillus species, B. schlegelii, B. tusciae,
      B. edaphicus and B. mucilaginosus were clearly placed outside the nine groups. 

PMID- 24031395
TI  - Molecular analysis of endophytic bacteria from the genus Bacillus isolated from
      tropical maize (Zea mays L.).
AB  - Endophytic bacteria play an important role in agriculture by improving plant
      performance and adaptation against biotic and abiotic stresses. In the present
      study molecular methods were used for identifying Bacillus endophytic bacteria
      isolated from Brazilian sweet corn. SDS-PAGE of whole-cell protein extract of
      forty-two isolates revealed a high number of scrutinable bands. Twenty-four
      isolates were identified in nine different groups of duplicated bacteria and
      eighteen were identified as unique. Some high-accumulated polipeptides with
      variable length were observed in almost isolates. Partial sequencing of 16S
      ribosomal gene revealed that all isolates are Bacillus sp. and among thirteen
      isolates with similar protein profiles, two were different strains. Among the
      forty-two isolates identified by rDNA sequencing, Bacillus subitilis and B.
      pumilus were the most frequenty species (15 and 12 isolates, respectively)
      followed by B. licheniformes (7 isolates), B. cereus (5 isolates) and B.
      amiloliquefascens (3 isolates). According to present results, SDS-PAGE technique
      could be used as a fast and cheap first tool for identifying inter-specific
      variation in maize endophytic bacterial collections while rDNA sequencing could
      be applied for analyzing intra-specific variation among isolates with similar
      protein profile as well as for taxonomic studies. 

PMID- 24031396
TI  - Determination of the antibacterial activity of crude extracts and compounds
      isolated from Hortia oreadica (Rutaceae) against oral pathogens.
AB  - Extracts from Hortia oreadica afforded four dihydrocinnamic acid derivatives,
      isolated from the n-hexane extract, as well as limonoid guyanin and the
      furoquinoline alkaloid dictamnine, both isolated from the dichloromethane
      extract. The extracts and the isolated compounds were tested against some oral
      pathogens, so as to investigate their antibacterial activity. The results showed
      that the n-hexane extract and the compound dictamnine are the most active against
      the selected microorganisms. 

PMID- 24031397
TI  - Evaluation of the sterilization efficacy of domestic electric drills used in
      orthopaedic surgeries.
AB  - It is estimated that electric drills (ED) have been used in orthopaedic surgeries
      for bone drilling for more than 50 years in Brazilian hospitals. It is an
      electric, thermosensitive equipment, not indicated for surgical use, which has
      not been previously evaluated regarding the sterilization efficacy, being suspect
      of infection risk. This study evaluated the efficacy of sterilization by ethylene
      oxide (EtO) of new drills that were intentionally contaminated with Bacillus
      atrophaeus spores. An experimental, laboratory, randomized applied research was
      developed, where 16 electric drills were analyzed, in addition to positive and
      negative controls. All the previously cleaned and sterilized equipment were
      submitted to contamination by spores. The experimental group was submitted to
      cleaning and sterilization by EtO and test of sterility by filtration through a
      0.45 >m membrane. The membranes were cultivated and Gram and Wirtz-Conklin
      staining were carried out in positive results for spore visualization. An
      efficacy of 99.99999881% of the process of sterilization by EtO was confirmed,
      with a probability of survival of 1.19 x 10 (-8). Under the development
      conditions of the experiment, the efficacy of the sterilization of ED by EtO was
      confirmed. 

PMID- 24031398
TI  - Bacteriophage: laboratorial diagnosis and phage therapy.
AB  - Bacteriophages have been researched as a new alternative to antibiotics. These
      viruses inject their genetic material into bacteria and use their host machinery
      to multiply themselves. The research of bacteriophages in Brazil will certainly
      provide low-cost treatment of multidrug resistant bacteria, new microbiological
      diagnosis and advantages for the Brazilian food industry. 

PMID- 24031400
TI  - Biotransformation of a cage-like diels-alder adduct and derivatives by Mucor
      ramosissimus samutsevitsch.
AB  - The present study aimed to evaluate the ability for biotransformation of the
      Diels-Alder adduct tricyclo[6.2.1.0(2,7)]undeca-4,9-dien-3,6-dione (1) and two
      synthetic derivatives by the saprobe fungus Mucor ramosissimus Samutsevitsch.
      Products from oxidation, isomerization and, regioselective and enantioselective
      reduction were achieved. 

PMID- 24031399
TI  - Aggregatibacter actinomycetemcomitans arcB influences hydrophobic properties,
      biofilm formation and adhesion to hydroxyapatite.
AB  - The regulation of gene expression in the oral pathogen Aggregatibacter
      actinomycetemcomitans is still not fully elucidated. ArcAB is a two-component
      system which allows facultative anaerobic bacteria to sense various respiratory
      growth conditions and adapt their gene expression accordingly.This study
      investigated in A. actinomycetemcomitans the role of ArcB on the regulation of
      biofilm formation, adhesion to saliva coated hydroxyapatite (SHA) and the
      hydrophobic properties of the cell. These phenotypic traits were determined for
      an A. actinomycetemcomitans arcB deficient type and a wild type strain.
      Differences in hydrophobic properties were shown at early and late exponential
      growth phases under microaerobic incubation and at late exponential phase under
      anaerobiosis.The arcB mutant formed less biofilm than the wild type strain when
      grown under anaerobic incubation, but displayed higher biofilm formation activity
      under microaerobic conditions. The adherence to SHA was significantly lower in
      the mutant when compared with the wild type strain. These results suggest that
      the transmembrane sensor kinase ArcB, in A. actinomycetemcomitans, senses redox
      growth conditions and regulates the expression of surface components of the
      bacterial cell related to biofilm formation and adhesion to saliva coated
      surfaces. 

PMID- 24031401
TI  - Occurrence of Salmonella spp. in broiler chicken carcasses and their
      susceptibility to antimicrobial agents.
AB  - The present study was carried out to evaluate the occurrence of Salmonellae in
      broiler chicken carcasses and to determine the antimicrobial resistance profile
      of the isolated strains. Twenty-five out of the 260 broiler chicken carcasses
      samples (9.6%) were positive for Salmonella. S. Enteritidis was the most frequent
      serovar. Nineteen Salmonella isolates were tested for antimicrobial resistance,
      and the results indicated that 94.7% were resistant to at least one antimicrobial
      agent. Resistance to streptomycin (73.7%), nitrofurantoin (52.3%), tetracycline
      (31.6%), and nalidixic acid (21%) were the prevalent amongst Salmonella strains
      tested. 

PMID- 24031402
TI  - Characterization of Listeria monocytogenes isolated from a fresh mixed sausage
      processing line in Pelotas-RS by PFGE.
AB  - Listeria monocytogenes is a bacterium capable to adhere to the surfaces of
      equipment and utensils and subsequently form biofilms. It can to persist in the
      food processing environmental for extended periods of time being able to
      contaminate the final product. The aim of this study was to trace the
      contamination route of L. monocytogenes on a fresh mixed sausage processing line,
      from raw material to the final product. The isolates obtained were characterized
      by serotyping and molecular typing by pulsed-field gel electrophoresis (PFGE)
      using the restriction enzymes ApaI and AscI. L. monocytogenes was detected in 25%
      of the samples. The samples of raw material were not contaminated, however, the
      microorganism was detected in 21% of the environmental samples (food contact and
      non-food contact), 20.8% of the equipments, 20% of the food worker's hands, 40%
      of the mass ready to packaging and in all the final products samples,
      demonstrating that the contamination of final product occurred during the
      processing and the importance of cross contamination. PFGE yielded 22 pulsotypes
      wich formed 7 clusters, and serotyping yielded 3 serotypes and 1 serogroup,
      however, the presence of serotypes 4b and 1/2b in the final product is of great
      concern for public health. The tracing of contamination showed that some strains
      are adapted and persisted in the processing environment in this industry. 

PMID- 24031403
TI  - Potential of chitosan from Mucor rouxxi UCP064 as alternative natural compound to
      inhibit Listeria monocytogenes.
AB  - Listeria monocytogenes is widely distributed in nature and the infection
      listeriosis is recognized as a potential threat for human health because of its
      mortality rate. The objective of this study was to evaluate the growth profile
      and chitosan production by Mucor rouxxi UCP 064 grown in yam bean (Pachyrhizus
      erosus L. Urban) medium. It was also to assess the anti-L. monocytogenes efficacy
      of the obtained chitosan. Higher values of biomass of M. rouxxi (16.9 g.L(-1))
      and best yield of chitosan (62 mg.g(-1)) were found after 48 h of cultivation.
      Residual glucose and nitrogen in the growth media were 4.1 and 0.02 g.L(-1) after
      96 h, respectively. Obtained chitosan presented 85 % of degree of deacetylation
      and 2.60 x 10(4) g.mol(-1) of viscosimetric molecular weight. Minimum Inhibitory
      Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values of
      chitosan against L. monocytogenes ATCC 7644 were, respectively, 2.5 and 5.0
      mg.mL(-1). At 2.5 and 5.0 mg.mL(-1) chitosan caused cidal effect in a maximum
      time of 4 h. Bacterial count below 2 log cfu.mL(-1) were found from 2 h onwards
      and no recovery in bacterial growth was noted in the remainder period. These
      results show the biotechnological potential of yam bean medium for chitosan
      production by Mucor rouxxi and support the possible rational use of chitosan from
      fungi as natural antimicrobial to control L. monocytogenes. 

PMID- 24031404
TI  - Microbial diversity in a bagasse-based compost prepared for the production of
      Agaricus brasiliensis.
AB  - Edible mushrooms are renowned for their nutritional and medicinal properties and
      are thus of considerable commercial importance. Mushroom production depends on
      the chemical composition of the basic substrates and additional supplements
      employed in the compost as well as on the method of composting. In order to
      minimise the cost of mushroom production, considerable interest has been shown in
      the use of agro-industrial residues in the preparation of alternative compost
      mixtures. However, the interaction of the natural microbiota present in
      agricultural residues during the composting process greatly influences the
      subsequent colonisation by the mushroom. The aim of the present study was to
      isolate and identify the microbiota present in a sugar cane bagasse and coast
      cross straw compost prepared for the production of Agaricus brasilienses.
      Composting lasted for 14 days, during which time the substrates and additives
      were mixed every 2 days, and this was followed by a two-step steam pasteurisation
      (55 - 65 degrees C; 15 h each step). Bacteria, (mainly Bacillus and Paenibacillus
      spp. and members of the Enterobacteriaceae) were the predominant micro-organisms
      present throughout the composting process with an average population density of 3
      x 10(8) CFU/g. Actinomycetes, and especially members of the genus Streptomyces,
      were well represented with a population density of 2 - 3 x 10(8) CFU/g. The
      filamentous fungi, however, exhibited much lower population densities and were
      less diverse than the other micro-organisms, although Aspergillus fumigatus was
      present during the whole composting process and after pasteurisation. 

PMID- 24031405
TI  - Microbial modeling of thermal resistance of Alicyclobacillus acidoterrestris
      CRA7152 spores in concentrated orange juice with nisin addition.
AB  - The nisin effect on thermal death of Alicyclobacillus acidoterrestris CRA 7152
      spores in concentrated orange juice (64 degrees Brix) was studied. Concentrations
      of 0, 50, 75 and 100 IU of nisin/ml juice, at temperatures of 92, 95, 98 and 102
      degrees C were evaluated. The quadratic polynomial model was used to analyze the
      effects of the factors and their interaction. Verification of surviving spores
      was carried out through plating in K medium (pH 3.7). The results showed that the
      D values without nisin addition were 25.5, 12.9, 6.1 and 2.3 min for 92, 95, 98
      and 102 degrees C respectively. With addition of nisin into the juice there was a
      drop of heat resistance as the concentration was increased at a same temperature.
      With 30, 50, 75, 100 and 150 IU/ml at 95 degrees C, the D values were 12.34,
      11.38, 10.49, 9.49 and 9.42 min respectively, showing that a decrease in the D
      value up to 27% can be obtained. The second order polynomial model established
      with r(2) = 0.995 showed that the microorganism resistance was affected by the
      action of temperature followed by the nisin concentration. Nisin therefore is an
      alternative for reducing the rigor of the A. acidoterrestris CRA 7152 thermal
      treatment. 

PMID- 24031406
TI  - Production of thermostable invertases by Aspergillus caespitosus under submerged
      or solid state fermentation using agroindustrial residues as carbon source.
AB  - The filamentous fungus Aspergillus caespitosus was a good producer of
      intracellular and extracellular invertases under submerged (SbmF) or solid-state
      fermentation (SSF), using agroindustrial residues, such as wheat bran, as carbon
      source. The production of extracellular enzyme under SSF at 30 degrees C, for
      72h, was enhanced using SR salt solution (1:1, w/v) to humidify the substrate.
      The extracellular activity under SSF using wheat bran was around 5.5-fold higher
      than that obtained in SbmF (Khanna medium) with the same carbon source. However,
      the production of enzyme with wheat bran plus oat meal was 2.2-fold higher than
      wheat bran isolated. The enzymatic production was affected by supplementation
      with nitrogen and phosphate sources. The addition of glucose in SbmF and SSF
      promoted the decreasing of extracellular activity, but the intracellular form
      obtained in SbmF was enhanced 3-5-fold. The invertase produced in SSF exhibited
      optimum temperature at 50 degrees C while the extra- and intracellular enzymes
      produced in SbmF exhibited maximal activities at 60 degrees C. All enzymatic
      forms exhibited maximal activities at pH 4.0-6.0 and were stable up to 1 hour at
      50 degrees C. 

PMID- 24031407
TI  - Production, purification and application of extracellular chitinase from
      Cellulosimicrobium cellulans 191.
AB  - This study concerned the production, purification and application of
      extracellular chitinase from Cellulosimicrobium cellulans strain 191. In shaken
      flasks the maximum yield of chitinase was 6.9 U/mL after 72 h of cultivation at
      25 degrees C and 200 rpm. In a 5 L fermenter with 1.5 vvm aeration, the highest
      yield obtained was 4.19 U/mL after 168 h of fermentation at 25 degrees C and 200
      rpm, and using 3 vvm, it was 4.38 U/mL after 144 h of fermentation. The chitinase
      (61 KDa) was purified about 6.65 times by Sepharose CL 4B 200 gel filtration with
      a yield of 46.61%. The purified enzyme was able to lyse the cell walls of some
      fungi and to form protoplasts. 

PMID- 24031408
TI  - Obtaining partial purified xylose reductase from Candida guilliermondii.
AB  - The enzymatic bioconversion of xylose into xylitol by xylose reductase (XR) is an
      alternative for chemical and microbiological processes. The partial purified XR
      was obtained by using the following three procedures: an agarose column, a
      membrane reactor or an Amicon Ultra-15 50K Centrifugal Filter device at yields of
      40%, 7% and 67%, respectively. 

PMID- 24031409
TI  - Exo-polygalacturonase production by Bacillus subtilis CM5 in solid state
      fermentation using cassava bagasse.
AB  - The purpose of this investigation was to study the effect of Bacillus subtilis
      CM5 in solid state fermentation using cassava bagasse for production of exo
      polygalacturonase (exo-PG). Response surface methodology was used to evaluate the
      effect of four main variables, i.e. incubation period, initial medium pH,
      moisture holding capacity (MHC) and incubation temperature on enzyme production.
      A full factorial Central Composite Design was applied to study these main factors
      that affected exo-PG production. The experimental results showed that the optimum
      incubation period, pH, MHC and temperature were 6 days, 7.0, 70% and 50 degrees
      C, respectively for optimum exo-PG production. 

PMID- 24031410
TI  - A thin layer electrochemical cell for disinfection of water contaminated with
      Staphylococcus aureus.
AB  - A thin layer electrochemical cell was tested and developed for disinfection
      treatment of water artificially contaminated with Staphylococcus aureus.
      Electrolysis was performed with a low-voltage DC power source applying current
      densities of 75 mA cm(-2) (3 A) or 25 mA cm(-2) (1 A). A dimensionally stable
      anode (DSA) of titanium coated with an oxide layer of 70%TiO2 plus 30%RuO2 (w/w)
      and a 3 mm from a stainless-steel 304 cathode was used in the thin layer cell.
      The experiments were carried out using a bacteria suspension containing 0.08 M
      sodium sulphate with chloride-free to determine the bacterial inactivation
      efficacy of the thin layer cell without the generation of chlorine. The chlorine
      can promote the formation of trihalomethanes (THM) that are carcinogenic. S.
      aureus inactivation increased with electrolysis time and lower flow rate. The
      flow rates used were 200 or 500 L h(-1). At 500 L h(-1) and 75 mA cm(-2) the
      inactivation after 60 min was about three logs of decreasing for colony forming
      units by mL. However, 100% inactivation for S. aureus was observed at 5.6 V and
      75 mA cm(-2) after 30 min. Thus, significant disinfection levels can be achieved
      without adding oxidant substances or generation of chlorine in the water. 

PMID- 24031411
TI  - Pseudomonas aeruginosa KUCD1, a possible candidate for cadmium bioremediation.
AB  - A cadmium (8 mM) resistant Pseudomonas aeruginosa strain KUCd1 exhibiting high Cd
      accumulation under in vitro aerobic condition has been reported. The isolate
      showed a significant ability to remove more than 75% and 89% of the soluble
      cadmium during the active growth phase from the growth medium and from Cd-amended
      industrial wastewater under growth supportive condition. Transmission electron
      microscopy (TEM) and energy dispersive X-ray spectroscopy (EDXS) suggest the
      presence of Cd in the cells from mid stationary phase. The cell fractionation
      study revealed membrane and periplasm to be the major accumulating site in this
      strain. The chemical nature of the accumulated Cd was studied by X-ray powder
      diffraction analysis. 

PMID- 24031412
TI  - Rapid polyvalent screening for largescale environmental Spiroplasma surveys.
AB  - Surface serology is an important determinant in Spiroplasma systematics.
      Reciprocal antigen/antibody reactions between spiroplasmas and individual
      antisera delineate the 38 described groups and species. However, reciprocal
      serology is impractical for large-scale studies. This report describes a
      successful, streamlined polyvalent screening approach used to examine isolates
      from an environmental survey. 

PMID- 24031413
TI  - Genetic variability of Brazilian isolates of Alternaria alternata detected by
      AFLP and RAPD techniques.
AB  - The Alternaria brown spot (ABS) is a disease caused in tangerine plants and its
      hybrids by the fungus Alternaria alternata f. sp. citri which has been found in
      Brazil since 2001. Due to the recent occurrence in Brazilian orchards, the
      epidemiology and genetic variability of this pathogen is still an issue to be
      addressed. Here it is presented a survey about the genetic variability of this
      fungus by the characterization of twenty four pathogenic isolates of A. alternata
      f. sp. citri from citrus plants and four endophytic isolates from mango (one
      Alternaria tenuissima and three Alternaria arborescens). The application of two
      molecular markers Random Amplified Polymorphic DNA (RAPD) and Amplified Fragment
      Length Polymorphism (AFLP) had revealed the isolates clustering in distinct
      groups when fingerprintings were analyzed by Principal Components Analysis (PCA).
      Despite the better assessment of the genetic variability through the AFLP,
      significant modifications in clusters components were not observed, and only
      slight shifts in the positioning of isolates LRS 39/3 and 25M were observed in
      PCA plots. Furthermore, in both analyses, only the isolates from lemon plants
      revealed to be clustered, differently from the absence of clustering for other
      hosts or plant tissues. Summarizing, both RAPD and AFLP analyses were both
      efficient to detect the genetic variability within the population of the
      pathogenic fungus Alternaria spp., supplying information on the genetic
      variability of this species as a basis for further studies aiming the disease
      control. 

PMID- 24031414
TI  - Low genetic diversity among pathogenic strains of Erwinia psidii from Brazil.
AB  - Erwinia psidii causes bacterial disease of guava in Brazil. Phenotypic and
      molecular characterization through rep-PCR fingerprinting of 42 strains from
      different geographical regions showed that E. psidii populations in Brazil have a
      low level of genetic diversity and suggest that contaminated plant material is
      the main source for pathogen dissemination in the country. 

PMID- 24031415
TI  - Molecular epidemiology of Shigella spp strains isolated in two different
      metropolitam areas of southeast Brazil.
AB  - Shigella spp., the human pathogen responsible for shigellosis, is highly
      infectious even at low levels. The incidence rate of shigellosis varies with
      geographical distribution, location human development index, and age groups,
      being higher among children aged under 5 years. In Brazil, a few works indicate
      that shigellosis cases are underestimated, with S. flexneri and S. sonnei strains
      being the major agents responsible for the shigellosis cases. The present study
      used pulsed field gel electrophoresis (PFGE) to investigate the molecular
      epidemiology of 119 strains of S. sonnei and S. flexneri isolated from
      shigellosis cases that occurred in the metropolitan areas of Ribeirao Preto and
      Campinas Cities, Sao Paulo Sate, southeast Brazil. The results indicated (i) the
      existence of just a few strain clusters for both species, but with genotype
      variability with either a high speed of genetic change or constant introduction
      of several genotypes, considering the intense migration to these two metropolitan
      areas, and (ii) the prevalence of specific genotypes in each geographical area,
      which suggests the successful adaptation of some genotypes to the local
      environmental conditions. Our results indicate the need of more efficacious
      sanitary barriers to prevent Shigella spp. outbreaks and epidemics. 

PMID- 24031416
TI  - Identification, antimicrobial resistance and genotypic characterization of
      Enterococcus spp. isolated in Porto Alegre, Brazil.
AB  - In the past two decades the members of the genus Enterococcus have emerged as
      important nosocomial pathogens worldwide. In the present study, we evaluated the
      antimicrobial resistance and genotypic characteristics of 203 Enterococcus spp.
      recovered from different clinical sources from two hospitals in Porto Alegre, Rio
      Grande do Sul, Brazil. The species were identified by conventional biochemical
      tests and by an automated system. The genetic diversity of E. faecalis presenting
      high-level aminoglycoside resistance (HLAR) was assessed by pulsed-field gel
      electrophoresis of chromosomal DNA after SmaI digestion. The E. faecalis was the
      most frequent specie (93.6%), followed by E. faecium (4.4%). The antimicrobial
      resistance profile was: 2.5% to ampicillin, 0.5% to vancomycin, 0.5% teicoplanin,
      33% to chloramphenicol, 2% to nitrofurantoin, 66.1% to erythromycin, 66.5% to
      tetracycline, 24.6% to rifampicin, 30% to ciprofloxacin and 87.2% to quinupristin
      dalfopristin. A total of 10.3% of the isolates proved to be HLAR to both
      gentamicin and streptomycin (HLR-ST/GE), with 23.6% resistant only to gentamicin
      (HLR-GE) and 37.4% only to streptomycin (HLR-ST). One predominant clonal group
      was found among E. faecalis HLR-GE/ST. The prevalence of resistance among beta
      lactam antibiotics and glycopeptides was very low. However, in this study there
      was an increased number of HLR Enterococcus which may be spreading intra and
      inter-hospital. 

PMID- 24031417
TI  - Proinflammatory signal transduction pathway induced by Shigella flexneri porins
      in caco-2 cells.
AB  - The recognition of bacterial components on the intestinal epithelial cells occurs
      through the toll-like receptors and is followed by the induction of an effective
      innate immune response. We analyzed receptor expression and signaling pathways
      involved in activation of human colon adenocarcinoma cells after stimulation with
      porins and LPS of Shigella flexneri. We also analyzed the expression and
      production of some cytokines, of intercellular adhesion molecule-1, of
      antimicrobial peptides human beta-defensins, and of the inducible form of nitric
      oxide synthase. Our data demonstrate that TLR2 is involved in porin recognition,
      whereas TLR4 with MD2, is required for LPS recognition. 

PMID- 24031418
TI  - Production of Poly-gamma-Glutamate (PGA) Biopolymer by Batch and Semicontinuous
      Cultures of Immobilized Bacilluslicheniformis strain-R.
AB  - Production of Polyglutamate (PGA) biopolymer by immobilized Bacillus
      licheniformis strain-R was intensively investigated. Preliminary experiments were
      carried out to address the most suitable immobilization methodology. Entrapment
      of Bacillus cells in alginate-agar led optimal PGA production (36.75 g/l), with
      1.32-and 2.18-fold increase in comparison with alginate-or K-carrageenan
      immobilized cells, respectively. During semicontinuous cultivation of agar
      alginate gel-cell mixture, production of PGA by 10 ml mixture was increased from
      2(nd) to 3(rd) run whereas, increased till the 4(th) run using 15ml mixture.
      Adsorption was the most suitable immobilization technique for production of PGA
      and the sponge cubes was the preferred matrix recording 43.2 g/l of PGA with the
      highest cell adsorption. Furthermore, no PGA was detected when B. licheniformis
      cells were adsorbed on wood and pumice. Although luffa pulp-adsorbed cells
      recorded the highest PGA production (50.4 g/l), cell adsorption was the lowest.
      Semicontinuous cultivation of B. licheniformis cells adsorbed on sponge led to
      increase of PGA production till the 3(rd) run and reached 55.5 g/l then slightly
      decreased in the 4(th) run. The successful use of fixed-bed bioreactor for
      semicontinuous cultivation of B. licheniformis cells held on sponge cubes (3
      runs, 96 hours/run) provides insight for the potential biotechnological
      production of PGA by immobilized cells. 

PMID- 24031419
TI  - Chitinase Production by Streptomyces sp. ANU 6277.
AB  - Chitinase production by a terrestrial Streptomyces sp. ANU 6277 was studied under
      sub-merged fermentation. Chitinase production started after 24 h of incubation
      and reached maximum levels after 60 h of cultivation. A high level of chitinase
      activity was observed in the culture medium with pH 6 at 35 degrees C. Culture
      medium amended with 1% chitin was found to be suitable for maximum production of
      chitinase. An optimum concentration of colloidal chitin for chitinase production
      was determined. Studies on the influence of additional carbon and nitrogen
      sources on chitinase production revealed that starch and yeast extract served as
      good carbon and nitrogen sources to enhance chitinase yield. Chitinase was
      purified from crude enzyme extract by single step gel filtration by Sephadex G
      100. Purified chitinase of the strain exhibited a distinct protein band near 45
      kDa by means of SDS-PAGE. 

PMID- 24031420
TI  - Effect of branched-chain amino acids, valine, isoleucine and leucine on the
      biosythesis of bitespiramycin 4"-O-acylspiramycins.
AB  - Bitespiramycin, a group of 4"-O-acylated spiramycins with 4"-O
      isovalerylspiramycins as the major components, was produced by recombinant
      spiramycin-producing strain Streptomyces spiramyceticus harboring a 4"-O
      acyltransferase gene. The experiment was initially performed in synthetic medium
      with 0.5 g l(-1) Valine, Isoleucine or Leucine feeding at 36 h cultivation. When
      valine was fed, the biological titer of bitespiramycin was 45.3% higher than that
      of the control group, but the relative content of total isovalerylspiramycin
      components decreased by 22.5%. In the case of ilecine, the biological titer of
      bitespiramycin and the total isovalerylspiramycins alone were 85% and 72.1% of
      the control group, respectively. In contrast, the relative content of other
      acylated spiramycins increased by 54.41%. However, leucine feeding increased the
      relative content of total isovalerylspiramycins by 41.9% while the biological
      titer of bitespiramycin was nearly equal to that of the control group. The
      improvement effect of leucine on the biosynthesis of isovalerylspiramycins was
      further confirmed by feeding of 2.0 g l(-1) leucine to the culture with complex
      medium. After batch feeding with a total amount of 2.0 g l(-1) leucine to the
      culture from 70 h to 90 h, the biological titer of bitespiramycin was almost
      unreduced, and the final relative content of total isovalerylspiramycins
      increased from 31.1% to 46.9%. 

PMID- 24031421
TI  - Screening of microbial lipases and evalutaion of their potential to produce
      glycerides with high gamma linolenic acid concentration.
AB  - Gamma linolenic acid (GLA, 18:3, cis- 6,9,12- octadecatrienoic acid), an
      important compound in n- 6 eicosanoid family biosynthesis, occurs in the lipids
      of a few plant and microbial sources. This study focused on the screening of
      microbial strains with suitable lipase activity for enrichment of GLA by
      selective hydrolysis of the borage oil (21.6 % of GLA/total fatty acids).
      Firstly, 352 microrganisms were tested for their lipolytic capacity using
      screening techniques on agar plates containing borage oil, strains were then
      selected and screened for their activity (U/mg) using both submerged fermentation
      (SmF) and solid state fermentation (SSF). The rate of hydrolysis and the
      selective preference of these hydrolytic enzymes towards fatty acids, with a
      special focus on enrichment of GLA were studied and compared with those obtained
      by two commercially-available lipases. Only one of the lipases tested during this
      study displayed selectivity, discriminating the GLA during the hydrolysis
      reaction. Using the enzymatic extract from Geotrichum candidum as a biocatalyst
      of the reaction, it was possible to obtain a percentage of 41.7% of GLA in
      acylglycerols fraction when the borage oil was treated in a fixed-bed reactor for
      24 hours at 30oC. 

PMID- 24031422
TI  - Antibacterial and Antioxidant Activities of Acid and Bile Resistant Strains of
      Lactobacillus fermentum Isolated from Miang.
AB  - Miang is a kind of traditional fermented tea leaves, widely consumed in northern
      Thailand as a snack. It contains several kinds of Lactobacilli spp. The aim of
      this study was to isolate strains of Lactobacillus fermentum from miang and to
      investigate their antibacterial and antioxidant activities. The agar spot and
      well assays were used for determination of antibacterial power. The antibacterial
      mechanism was investigated by cell morphologic change under scanning electron
      microscope (SEM). Antioxidant activity was studied by means of free radical
      scavenging and ferric reducing power assays. The acid and bile screening tests
      indicated that L. fermentum FTL2311 and L. fermentum FTL10BR presented
      antibacterial activity against several pathogenic bacteria: Listeria
      monocytogenes DMST 17303, Salmonella Typhi DMST 5784, Shigella sonnei DMST 561
      (ATCC 11060) and Staphylococcus aureus subsp. aureus DMST 6512 (ATCC 6538Ptm).
      The results from SEM suggested that the antibacterial action was due to the
      destruction of cell membrane which consequently caused the pathogenic cell
      shrinking or cracking. The antioxidant study suggested that both L. fermentum
      FTL2311 and L. fermentum FTL10BR strains could liberate certain substances that
      possessed antioxidant activity expressed as trolox equivalent antioxidant
      capacity (TEAC) and equivalent concentration (EC) values for free radical
      scavenging and reducing mechanisms, respectively. The supernatant of L. fermentum
      FTL2311 broth revealed TEAC and EC values of 22.54+/-0.12 and 20.63+/-0.17 >M.mg(
      1) respectively, whereas that of L. fermentum FTL10BR yielded TEAC and EC values
      of 24.09+/-0.12 and 21.26+/-0.17 >M.mg(-1) respectively. These two strains
      isolated from miang present high potential as promising health-promoting
      probiotics. 

PMID- 24031423
TI  - Effect of lysozyme or nisin on survival of some bacteria treated with high
      pressure at subzero temperature.
AB  - The aim of this work was to examine the inactivation of some Gram-positive and
      Gram-negative bacteria exposed to the pressure of 193 MPa at -20  degrees C in
      the presence of lysozyme or nisin at concentration of 400 ug/ml. The highest
      effect of pressure at subzero temperature and lysozyme was found with pressure
      sensitive Pseudomonas fluorescens; viable cells of this strain were not detected
      in 1 ml of sample after combined treatment. The action of pressure at subzero
      temperature and lysozyme or nisin against Escherichia coli led to synergistic
      reduction by 0.7 or 1.6 log cycles, respectively, while it was practically
      insignificant for two Staphylococcus aureus strains. Viability loss of E. coli
      and S. aureus occurred during storage for 20 h of the samples at 37 and 5 
      degrees C, which were previously pressurized with lysozyme or nisin. The
      synergistic effect of pressure and nisin at pH 5 against E. coli cells just after
      the pressure treatment was lower than that at pH 7, however, the extent of the
      lethal effect after storage was higher. 

PMID- 24031424
TI  - New vectors derives from pUC 18 for clonig and thermal-induced expression in
      Escherichia coli.
AB  - We report the construction of two vectors for Escherichia coli: pUC72, for
      molecular cloning, and pPLT7, for thermal-induced expression. The main feature of
      pUC72 is a novel polylinker region that includes restriction sites for Nde I and
      Nco I which provide an ATG codon for proper translation initiation of expressed
      genes. Vector pPLT7 is ideal for thermo-inducible expression in host cells that
      carry the cI857 repressor gene. The use of pPLT7 was validated by the successful
      expression of the genes encoding carp and porcine growth hormones. These vectors
      provide novel cloning possibilities in addition to simple, non-expensive, high
      level expression of recombinant proteins in E. coli. 

PMID- 24031425
TI  - Characterization And Application Of Tannase Produced By Aspergillus Niger ITCC
      6514.07 On Pomegranate Rind.
AB  - Extracellular tannase and gallic acid were produced optimally under submerged
      fermentation at 37 (0)C, 72 h, pH 5.0, 10 %(v/v) inoculum and 4 %(w/v) of the
      agroresidue pomegranate rind (PR) powder by an Aspergillus niger isolate. Tannic
      acid (1 %) stimulated the enzyme production by 245.9 % while with 0.5 % glucose,
      increase was marginal. Tannase production was inhibited by gallic acid and
      nitrogen sources such as NH4NO3, NH4Cl, KNO3, asparatic acid, urea and EDTA. The
      partially purified enzyme showed temperature and pH optima of 35 (0)C and 6.2
      respectively which shifted to 40 (0)C and 5.8 on immobilization in alginate
      beads. Activity of the enzyme was inhibited by Zn(+2), Ca(+), Mn(+2), Mg(+2),
      Ba(+2)and Ag(+). The immobilized enzyme removed 68.8 % tannin from juice of
      aonla/myrobalan (Phyllanthus emblica), a tropical fruit, rich in vitamin C and
      other essential nutrients. The enzymatic treatment of the juice with minimum
      reduction in vitamin C is encouraging as non enzymatic treatments of myrobalan
      juice results in vitamin C removal. 

PMID- 24031426
TI  - Production of laccase by Pynoporus sanguineus using 2,5 - Xylidine and ethanol.
AB  - Enzyme application in biotechnological and environmental processes has had
      increasing interest due to its efficiency, selectivity and mainly for being
      environmentally healthful, but these applications require a great volume of
      enzymes. In this work the effect of different concentrations of ethanol and 2,5
      xylidine on growth and production of laccase by Pycnoporus sanguineus was
      investigated. In a medium containing 200 mg.L(-1) of 2,5-xylidine or 50 g.L(-1)
      of ethanol, the maximum activity of laccase was 2019 U.L(-1) and 1035 U.L(-1),
      respectively. No direct correlation between biomass and activity of laccase was
      observed for any of the inducers used during the tests. Ethanol concentrations,
      larger than or equal to 20 g.L(-1), inhibited the radial growth of P. sanguineus.
      This study showed that ethanol, which has less toxicity and cost than the
      majority of the studied inducers, presents promising perspectives for laccase
      production by P. sanguineus. 

PMID- 24031427
TI  - Purification and characterisation of an extracellular phytase from Aspergillus
      niger 11T53A9.
AB  - An extracellular phytase from Aspergillus niger 11T53A9 was purified about 51
      fold to apparent homogeneity with a recovery of 20.3% referred to the phytase
      activity in the crude extract. Purification was achieved by ammonium sulphate
      precipitation, ion chromataography and gel filtration. The purified enzyme
      behaved as a monomeric protein with a molecular mass of about 85 kDa and
      exhibited maximal phytate-degrading activity at pH 5.0. Optimum temperature for
      the degradation of phytate was 55 degrees C. The kinetic parameters for the
      hydrolysis of sodium phytate were determined to be KM = 54 umol l(-1) and kcat =
      190 sec(-1) at pH 5.0 and 37 degrees C. The purified enzyme was rather specific
      for phytate dephosphorylation. It was shown that the phytase preferably
      dephosphorylates myo-inositol hexakisphosphate in a stereospecific way by
      sequential removal of phosphate groups via D-Ins(1,2,4,5,6)P5, D-Ins(1,2,5,6)P4,
      D-Ins(1,2,6)P3, D-Ins(1,2)P2 to finally Ins(2)P. 

PMID- 24031428
TI  - Decolorization of different textile dyes by Penicillium simplicissimum and
      toxicity evaluation after fungal treatment.
AB  - The objective of this study was to investigate the capacity of decolorization and
      detoxification of the textile dyes Reactive Red 198 (RR198), Reactive Blue 214
      (RB214), Reactive Blue 21 (RB21) and the mixture of the three dyes (MXD) by
      Penicillium simplicissimum INCQS 40211. The dye RB21, a phthalocyanine, was
      totally decolorized in 2 days, and the others, the monoazo RR198, the diazo RB214
      and MXD were decolorized after 7 days by P. simplicissimum. Initially the dye
      decolorization involved dye adsorption by the biomass followed by degradation.
      The acute toxicity after fungal treatment was monitored with the microcrustacean
      Daphnia pulex and measured through Effective Concentration 50% (EC50). P.
      simplicissimum reduced efficiently the toxicity of RB21 from moderately acutely
      toxic to minor acutely toxic and it also reduced the toxicity of RB214 and MXD,
      which remained minor acutely toxic. Nevertheless, the fungus increased the
      toxicity of RR198 despite of the reduction of MXD toxicity, which included this
      dye. Thus, P. simplicissimum INCQS 40211 was efficient to decolorize different
      textile dyes and the mixture of them with a significant reduction of their
      toxicity. In addition this investigation also demonstrated the need of
      toxicological assays associated to decolorization experiments. 

PMID- 24031429
TI  - Purification and Partial characterization of manganese peroxidase from Bacillus
      pumilus AND Paenibacillus sp.
AB  - The production of manganese peroxidase (MnP) from Bacillus pumilus and
      Paenibacillus sp. was studied under absence and presence of the inducers indulin
      AT, guayacol, veratryl alcohol, lignosulfonic acid and lignosulfonic acid
      desulfonated. Indulin AT increased the activity of B. pumilus MnP up to 31.66 U/L
      after 8 h, but no improve was observed for Paenibacillus sp., which reached
      maximum activity (12.22 U/L) after 20 h. Both MnPs produced by these
      microorganisms were purified in phenyl sepharose resin and the proteins from
      crude extracts were eluted in two fractions. However, only the first fraction of
      each extract exhibited MnP activities. Tests in different pH and temperature
      values, from pH 5.0 to pH 10.0 and 30  degrees C to 60  degrees C, respectively,
      were carried out with the purified MnP. The maximum activity reached for B.
      pumilus and Paenibacillus sp. MnPs were 4.3 U/L at pH 8.0 and 25  degrees C and
      11.74 U/L at pH 9.0 and 35  degrees C, respectively. The molar masses determined
      by SDS-PAGE gel eletrophoresis were 25 kDa and 40 kDa, respectively, for the
      purified enzyme from B. pumilus and Paenibacillus sp. 

PMID- 24031430
TI  - Phylogenetic analysis on the soil bacteria distributed in karst forest.
AB  - Phylogenetic composition of bacterial community in soil of a karst forest was
      analyzed by culture-independent molecular approach. The bacterial 16S rRNA gene
      was amplified directly from soil DNA and cloned to generate a library. After
      screening the clone library by RFLP, 16S rRNA genes of representative clones were
      sequenced and the bacterial community was analyzed phylogenetically. The 16S rRNA
      gene inserts of 190 clones randomly selected were analyzed by RFLP and generated
      126 different RFLP types. After sequencing, 126 non-chimeric sequences were
      obtained, generating 113 phylotypes. Phylogenetic analysis revealed that the
      bacteria distributed in soil of the karst forest included the members assigning
      into Proteobacteria, Acidobacteria, Planctomycetes, Chloroflexi (Green nonsulfur
      bacteria), Bacteroidetes, Verrucomicrobia, Nitrospirae, Actinobacteria (High G+C
      Gram-positive bacteria), Firmicutes (Low G+C Gram-positive bacteria) and
      candidate divisions (including the SPAM and GN08). 

PMID- 24031431
TI  - Adaptive and cross-protective responses against cadmium and zinc toxicity in
      cadmium-resistant bacterium isolated from a zinc mine.
AB  - Cadmium (Cd) is a major environmental hazard, which usually is detected in its
      ionic form of Cd(2+). It also causes adverse toxic effects on human health and
      other living organisms. Cd-resistant bacteria were isolated from Cd-contaminated
      soils. One isolate, TAK1, was highly resistance level to Cd toxicity. TAK1 was
      isolated from soil contaminated with a high Cd concentration (204.1 mg.kg(-1)).
      The result of 16S rDNA sequence analysis found that the TAK1 showed the
      similarity to Ralstonia sp. Physiological adaptive and cross-protective responses
      to Cd and Zn killing were investigated in Ralstonia sp.TAK1. Exposure to a low
      concentration of Cd induced adaptive resistance to higher concentrations of Cd.
      In addition, pretreatment of Ralstonia sp.TAK1 with an inducing concentration of
      Cd conferred cross-protective response against subsequent exposure to the lethal
      concentrations of Zn. The induced adaptive and cross-protective response
      Ralstonia sp.TAK1 required newly synthesized protein(s). Cd-induced adaptive and
      cross-protective responses against Cd and Zn toxicity are the important
      mechanisms used by Ralstonia sp.TAK1 to survive in the heavy metal-contaminated
      environments. These findings might lead to the use of Ralstonia sp.TAK1 for
      microbial based remediation in Cd and Zn-contaminated soils. 

PMID- 24031432
TI  - Agaricales Fungi from atlantic rain forest fragments in Minas Gerais, Brazil.
AB  - Two Atlantic Rain Forest fragments in Minas Gerais state were studied to access
      their Agaricales fungal richness. A total of 187 specimens were collected and 109
      species, 39 genera, and eight families were identified. Thirty-three species were
      cited for the first time in Brazil. 

PMID- 24031433
TI  - Genetic diversity of indigenous common bean (Phaseolus vulgaris L.) rhizobia from
      the state of Minas Gerais, Brazil.
AB  - We characterized indigenous common bean rhizobia from five districts of the state
      of Minas Gerais, Brazil. The isolates were trapped by two common bean varieties,
      the Mineiro Precoce (Andean origin) and Ouro Negro (Mesoamerican origin).
      Analysis by BOX-PCR of selected isolates detected a high level of genetic
      diversity. 

PMID- 24031434
TI  - Virioplankton abundance in trophic gradients of an upwelling field.
AB  - This work correlates time series of biological and physical variables to the
      marine viruses across trophic gradients within Arraial do Cabo upwelling system,
      Southeast of Brazil. The objective is to investigate the major controlling
      factors of virioplankton dynamics among different water masses. It was used an in
      situ and ex situ flow cytometry for accessing the plankton community. Viruses
      were highly correlated to bacteria and phytoplankton, but although the lack of
      direct correlation with physicals, upwelling turned out to be the main
      contributing factor to the highest values of viral abundance and virus:bacterial
      ratio. Our data suggest that the lowest temperature of upwelled South Atlantic
      Central Waters would help to maintain a high viral abundance and higher
      temperatures of Coastal and Tropical Waters might be another ecological niche
      allowing the co-existence. 

PMID- 24031435
TI  - Quantification of natural populations of Gluconacetobacter diazotrophicus and
      Herbaspirillum spp. In sugar cane (Saccharum spp.) Using differente polyclonal
      antibodies.
AB  - The species Gluconacetobacter diazotrophicus, Herbaspirillum seropedicae and H.
      rubrisubalbicans are endophytic N2-fixing [diazotrophic] bacteria which colonise
      not only roots, but also the aerial tissue of sugar cane. However, the technique
      most commonly used to quantify the populations of these microbes in plants is by
      culturing serial dilutions of macerates of plant tissues in N free semi-solid
      media which are only semi-selective for the species/genera [the Most Probable
      Number (MPN) Technique] and each culture must be further subjected to several
      tests to identify the isolates at the species level. The use of species-specific
      polyclonal antibodies with the indirect ELISA (enzyme-linked immunosorbent assay)
      can be an alternative which is rapid and specific to quantify these populations
      of bacteria. This study was performed to investigate the viability of adapting
      the indirect ELISA technique to quantify individually the populations of these
      three species of diazotroph within the root and shoot tissues of sugarcane. The
      results showed that species-specific polyclonal antibodies could be obtained by
      purifying sera in protein-A columns which removed non-specific immuno-globulins.
      It was possible to quantify the three bacterial species in the Brazilian
      sugarcane variety SP 70-1143 in numbers above 10(5) cells per g fresh weight in
      roots, rhizomes and leaves. The numbers of the different bacterial species
      evaluated using the ELISA technique were found to be higher than when the same
      populations were evaluated using the MPN technique, reaching 1400 times greater
      for G. diazotrophicus and 225 times greater for Herbaspirillum spp. These results
      constitute the first quantification of Herbaspirillum using immunological
      techniques. 

PMID- 24031436
TI  - In vitro degradation of linamarin by microorganisms isolated from cassava
      wastewater treatment lagoons.
AB  - This study aimed at isolating and characterizing of microorganisms able to use
      linamarin as sole carbon source. Thirty one microbial strains were isolated from
      manipueira, a liquid effluent of cassava processing factories. Among these
      strains, Bacillus licheniformis (isolate 2_2) and Rhodotorulla glutinis (isolate
      L1) were able to degrade 71% and 95% of added linamarin, respectively, within 7
      days, showing high biodegradation activity and great potential for detoxification
      of cassava processing wastewaters. 

PMID- 24031437
TI  - Degradation of Benzo [a] Pyrene by a novel strain Bacillus subtilis BMT4i (MTCC
      9447).
AB  - Benzo [a] Pyrene (BaP) is a highly recalcitrant, polycyclic aromatic hydrocarbon
      (PAH) with high genotoxicity and carcinogenicity. It is formed and released into
      the environment due to incomplete combustion of fossil fuel and various
      anthropogenic activities including cigarette smoke and automobile exhausts. The
      aim of present study is to isolate bacteria which can degrade BaP as a sole
      source of carbon and energy. We have isolated a novel strain BMT4i (MTCC 9447) of
      Bacillus subtilis from automobile contaminated soil using BaP (50 g /ml) as the
      sole source of carbon and energy in basal salt mineral (BSM) medium. The growth
      kinetics of BMT4i was studied using CFU method which revealed that BMT4i is able
      to survive in BaP-BSM medium up to 40 days attaining its peak growth (10(29) fold
      increase in cell number) on 7 days of incubation. The BaP degradation kinetics of
      BMT4i was studied using High Performance Liquid Chromatography (HPLC) analysis of
      BaP biodegradation products. BMT4i started degrading BaP after 24 hours and
      continued up to 28 days achieving maximum degradation of approximately 84.66 %.
      The above findings inferred that BMT4i is a very efficient degrader of BaP. To
      our best of knowledge, this is the first report showing utilization of BaP as a
      sole source of carbon and energy by bacteria. In addition, BMT4i can degrade a
      wide range of PAHs including naphthalene, anthracene, and dibenzothiophene
      therefore, it could serve as a better candidate for bioremediation of PAHs
      contaminated sites. 

PMID- 24031438
TI  - Isolation and identification of Profenofos degrading bacteria.
AB  - An enrichment culture technique was used to isolate bacterial strains responsible
      for the biodegradation of profenofos in a soil from Hubei province of central
      China. Two pure bacterial cultures, named W and Y, were isolated and subsequently
      characterized by sequencing of 16S rRNA genes and biochemical tests. Isolate W
      showed 96% similarity to the 16S rRNA gene of a Pseudomonas putida unlike Y which
      showed 99% similarity to the 16S rRNA gene of Burkholderia gladioli. Both strains
      grew well at pH 5.5-7.2 with a broad temperature profile ranging from 28 degrees 
      to 36  degrees C. Bioremediation of profenofos-contaminated soil was examined
      using soil treated with 200 ug g(-1); profenofos resulted in a higher degradation
      rate than control soils without inoculation. In a mineral salt medium (FTW)
      reduction in profenofos concentration was 90% within 96 hours of incubation. A
      literature survey revealed that no data is available regarding the role of
      Burkholderia gladioli on pesticide biodegradation as well as on profenofos. 

PMID- 24031439
TI  - Antineoplasic activity of Agaricus brasiliensis basidiocarps on different
      maturation phases.
AB  - The fungus Agaricus brasiliensis is a Basidiomycete studied because of its
      immunomodulation and/or antitumor substances. The objective of this study was to
      verify the Agaricus brasiliensis antineoplasic activity in vivo on different
      basidiocarp maturation phases on Sarcoma 180 cells implanted in mice. Sarcoma
      cells were implanted in mice and after seven days mice were divided in three
      groups. The first group was treated with saline solution, the second group was
      treated with closed basidiocarp extract solution and the third group was treated
      with opened basidiocarp extract solution. After 30 days of being daily orally
      treated with these three solutions all animals suffered euthanasia, and the
      splenic index, tumor mass and volume were determined. No significant differences
      of the tumor growth inhibition in function of the different basidiocarp
      maturation phases for the Agaricus brasiliensis strain were observed. The in vivo
      basidiocarp antineoplasic average activity was 89.22%. 

PMID- 24031440
TI  - Isolation, Purification and Evaluation of Antibacterial Agents from Aloe vera.
AB  - The ethanol, methanol and acetone extracts of Aloe vera gel were studied for
      their antimicrobial activity against four Gram-positive and Gram-negative
      bacteria using agar well diffusion method. The extracts showed varied levels of
      antimicrobial activity against the tested pathogens. The ethanol and methanol
      extracts showed higher activity while acetone extract, showed least or no
      activity against most of the tested pathogens. Fractions obtained from the
      extracts by Thin Layer and Column Chromatography were studied for their
      antagonistic properties using Spot Assay Technique. Compounds with maximum
      antibacterial activity isolated from the ethanol and methanol extracts were
      identified as p - coumaric acid (Mol. wt.165), ascorbic acid (Mol. wt.177 ),
      pyrocatechol (Mol. wt.110 ) and cinnamic acid (Mol. wt.148), on the basis of Gas
      Chromatography Mass Spectrometry. The study suggests the antimicrobial activity
      of the A. vera gel extract to be dependant on the synergistic effect of different
      compounds. With the broad spectral antimicrobial effect of A. vera gel, it could
      be further recommended in the treatment of various bacterial diseases. 

PMID- 24031441
TI  - Antimicrobial and toxicological studies of some metal complexes of 4
      methylpiperazine-1-carbodithioate and phenanthroline mixed ligands.
AB  - A few mixed ligand transition metal carbodithioate complexes of the general
      formula [M(4-MPipzcdt)x(phen)y]Y (M = Mn(II), Co(II), Zn(II); 4-MPipzcdt = 4
      methylpiperazine-1-carbodithioate; phen = 1,10-phenanthroline; x = 1 and y = 2
      when Y = Cl; x = 2 and y = 1 when Y = nil) were synthesized and screened for
      their antimicrobial activity against Candida albicans, Escherichia coli,
      Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis by disk
      diffusion method. All the complexes exhibited prominent antimicrobial activity
      against tested pathogenic strains with the MIC values in the range <8-512 gmL(
      1). The complexes [Mn(4-MPipzcdt)2(phen)] and [Co(4-MPipzcdt)(phen)2]Cl inhibited
      the growth of Candida albicans at a concentration as low as 8 ugmL(-1). The
      complexes were also evaluated for their toxicity towards human transformed
      rhabdomyosarcoma cells (RD cells). Moderate cell viability of the RD cells was
      exhibited against the metal complexes. 

PMID- 24031442
TI  - Glass bead transformation method for gram-positive bacteria.
AB  - A simple, inexpensive and reproducible transformation method was developed for
      Gram-positive bacteria. It was based on agitation of bacterial protoplasts with
      glass beads in the presence of DNA and polyethylene glycol. By using this method,
      introduction of pGK12 into protoplasts of several strains of Gram-positive
      bacteria was achieved. 

PMID- 24031443
TI  - Molecular characterization of Verocytotoxigenic Escherichia coli O157:H7 isolates
      from Argentina by Multiple-Loci VNTR Analysis (MLVA).
AB  - The aim of this work was to adapt described MLVA protocols to the molecular
      typing and characterization of VTEC O157:H7 isolates from Argentina. Nine VNTR
      loci were amplified by PCR showing diversity values from 0.49 to 0.73. Nine MLVA
      profiles were observed and the cluster analysis indicated both unrelated and
      closely related VTEC O157:H7 strains. In spite of the limited number of isolates
      studied, the panel of VNTR used made it possible to perform a first approach of
      the high genetic diversity of native strains of O157:H7 by MLVA. 

PMID- 24031444
TI  - Mechanism of Sterigmatocystin Biosynthesis Regulation by pH in Aspergillus
      nidulans.
AB  - External pH constitutes one of the most important environmental factors that
      control growth, metabolism and differentiation in microorganisms, including
      fungi. We have analyzed the effect of external pH on sterigmatocystin
      biosynthesis in Aspergillus nidulans. It was observed in repeated experiments
      that alkaline pH, in opposition to acid pH, increased sterigmatocystin production
      and the transcript levels of aflR, the master gene that regulates expression of
      the sterigmatocystin cluster in A. nidulans. It is known that pH effects in fungi
      operate mostly through the Pal/Pac signaling pathway, originally described in
      Aspergillus nidulans. Accordingly, we studied the role of this signaling pathway
      in ST biosynthesis. It was observed that aflR transcript levels were increased in
      the "alkalinity mimicking" mutant pacC(c)14 and were minimal in the "acidity
      mimicking" mutant palA1. No sterigmatocystin was produced by palA1 or pacC-
      mutants at neither acid or alkaline pH of incubation. Finally, fluG and flbA,
      genes known to regulate both conidiation and sterigmatocystin synthesis upstream
      in the regulatory cascade, were up-regulated at alkaline pH. 

PMID- 24031445
TI  - Mutants with heteroresistance to amphotericin B and fluconazole in Candida.
AB  - Several studies have reported the occurrence of infections caused by Candida
      yeasts as well as the increasing prevalence of non albicans species. The aim of
      the present work is focused on the obtaining of heteroresistance to amphotericin
      B and fluconazole in Candida species using two distinct methodologies: selection
      and induction. Resistant samples were obtained by selective pressure using a
      medium with fluconazole for growth, followed by growth in a medium with
      amphotericin B. The selective pressure was also created beginning with growth in
      amphotericin B medium followed by growth in fluconazole medium. Concomitantly,
      samples were submitted to the induction of resistance through cultivation in
      increasing concentrations of fluconazole, followed by cultivation in increasing
      concentrations of amphotericin B. Subsequently, the induction began with
      amphotericin B followed by fluconazole. Three samples resistant to fluconazole
      and amphotericin B were obtained, two by induction (C. glabrata and C.
      tropicalis) and one by selection (C. tropicalis). Both C. tropicalis originated
      from the same wild sample. After successive transfers for drug free medium, only
      the sample obtained by selection was able to maintain the resistance phenotype.
      These results suggest that the phenotype of heteroresitance to fluconazole and
      amphotericin B can be produced by two methodologies: selection and induction. 

PMID- 24031446
TI  - Use of pcr-rflp of the fla a gene for detection and subtyping of Campylobacter
      jejuni strains Potentially related to Guillain-barre syndrome, isolated from
      humans and animals.
AB  - The objectives of the present study were the subtyping of Campylobacter jejuni
      subsp. jejuni strains obtained from humans and different animal species using PCR
      RFLP, and the detection, by means of the same technique, of strains related to
      serotype PEN O19:LIO 7, the main C. jejuni serotype linked to Guillain-Barre
      Syndrome (GBS). Seventy C. jejuni strains isolated from human feces (n=33),
      primates (n=15), dogs (n=5), swine (n=2), bovines (n=1), abortion material from
      goats (n=2) and poultry carcasses (n=12), all collected in the state of Sao
      Paulo, were subtyped by means of PCR-RFLP of fla A gene, using restriction
      endonucleases Hae III, Afa I and Mbo I. Seven subtypes were observed when using
      the enzyme Hae III; eight when using Mbo I; and seven when using Afa I. The
      combination of the three endonucleases led to 16 fla-RFLP subtypes, from which
      ten subtypes shared strains of human and animal origin. From these, seven
      subtypes were observed in human and broiler strains. In eight subtypes, the other
      animal species shared patterns with human strains. It was inferred that, besides
      broilers, swine, goats, dogs and primates may be sources of infection for human
      in Sao Paulo. PCR-RFLP is a highly discriminatory technique that may be applied
      to molecular epidemiology studies of samples from different origins. Besides, the
      study also enabled the detection of two human strains and two primate strains
      related to serotype PEN O19: LIO 7. 

PMID- 24031447
TI  - Influence of probiotics on Candida presence and IgA anti-Candida in the oral
      cavity.
AB  - Probiotics are defined as microorganisms that promote benefits to host health,
      mainly by regulating resident microbiota. Disequilibrium in microbiota can favor
      the growth of opportunist microorganisms and the development of pathologies, like
      candidosis caused by yeasts of the Candida genus. This work evaluated whether
      probiotics consumption was able to influence a specific immunological response to
      Candida and the presence of these yeasts in the oral cavity. Saliva samples were
      collected from healthy individuals and plated in Dextrose Saboraud Agar with
      chloramphenicol. Individuals presenting Candida in the oral cavity used the
      probiotic Yakult LB(r) for 20 days, after which new collections and
      identifications were performed. Anti-Candida IgA analysis was conducted using the
      ELISA technique. Analysis of the results showed a significant reduction in
      Candida prevalence (46%) and mean Candida CFU/mL counts (65%). The Candida
      species identified were C. albicans (98%) and C. tropicalis (2%), before and
      after probiotics consumption. Immunological analysis demonstrated a significant
      reduction in anti-Candida IgA levels after probiotics use, probably due to less
      antigenic stimulation. In conclusion, in the individuals studied, probiotics use
      significantly reduced the amount of Candida in the oral cavity, possibly due to
      competition between the yeasts rather than by specific secretory immune response
      stimulation. 

PMID- 24031448
TI  - Prevalence of the precore G1896A mutation in Chinese patients with e antigen
      negative hepatitis B virus infection and its relationship to pre-S1 antigen.
AB  - This study investigated the prevalence of the precore G1896A mutation in Chinese
      patients with hepatitis B e antigen (HBeAg) negative HBV infection and its
      relation to serum HBV pre-S1 antigen. The overall prevalence of the precore
      G1896A mutation was 72.6% in HBeAg-negative Chinese patients with detectable
      serum HBV DNA. The prevalence of the precore G1896A is significantly higher in
      Chinese HBeAg-negative patients with chronic hepatitis B than that in inactive
      HBV carriers with detectable serum HBV DNA. Serum pre-S1 and the precore G1896A
      mutation were simultaneously detected in most of Chinese HBeAg-negative patients.

PMID- 24031449
TI  - Characterization of recombinant MSP5 Anaplasma marginale Havana isolate.
AB  - Anaplasma marginale is the causative agent of bovine anaplasmosis, a disease of
      worldwide economic importance. Major surface proteins (MSPs) are involved in host
      pathogen and tick-pathogen interactions and they have been used as markers for
      the genetic characterization of A. marginale strains and phylogenetic studies.
      The major surface protein 5 (MSP5) is highly conserved in the genus Anaplasma and
      in all isolates of A. marginale. The aim of the present work was to carry out the
      cloning, sequencing and characterization of the recombinant MSP5 Anaplasma
      marginale Havana isolate. The sequence of the msp5 gene of Anaplasma marginale
      Havana isolate with a size of 633 pb was determined (Acc. No. AY527217). This
      gene was cloned into pRSETB vector and expressed in Escherichia coli. The MSP5
      protein was recognized by the monoclonal antibody ANAF16C1 and it showed a high
      similitude percent with the gene sequence described for other Anaplasma marginale
      isolates. These data are very important for the development of a diagnostic test
      for A. marginale using the MSP5 recombinant protein. 

PMID- 24031450
TI  - Postantibiotic effects and postantibiotic sub-MIC effects of tilmicosin,
      erythromycin and tiamulin on erythromycin-resistant Streptococcus suis.
AB  - The postantibiotic effects (PAEs) and postantibiotic sub-MIC effects (PA SMEs) of
      tilmicosin, erythromycin and tiamulin on erythromycin-susceptible and
      erythromycin-resistant strains of Streptococcus suis (M phenotype) were
      investigated in vitro. Tilmicosin and tiamulin induced significantly longer PAE
      and PA SME against both erythromycin-susceptible and erythromycin-resistant
      strains than did erythromycin. The durations of PAE and PA SMEs were proportional
      to the concentrations of drugs used for exposure. The PA SMEs were substantially
      longer than PAEs on S. suis (P<0.05) regardless of the antimicrobial used for
      exposure. The results indicated that the PAE and PA SME could help in the design
      of efficient control strategies for infection especially caused by erythromycin
      resistant S. suis and that they may provide additional valuable information for
      the rational drug use in clinical practice. 

PMID- 24031451
TI  - A RT-PCR assay for the detection of encephalomycarditis virus infections in pigs.
AB  - Encephalomyocarditis virus (EMCV) infections can cause losses in pig farms all
      over the world. Rapid, sensitive and unequivocal detection of this virus is
      therefore essential for the diagnosis and control of the disease. An RT-PCR assay
      was developed, optimized and evaluated for encephalomyocarditis virus detection
      in organ based on a pair of primers that amplifies a 165 bp DNA fragment from a
      highly conserved nucleotide region of the viral 3D glycoprotein. PCR products of
      the expected size were obtained from Cuban EMCV 744/03 strain. Non-specific
      reactions were not observed when other porcine RNA genome viruses and uninfected
      cells were used. The analytical sensitivity of the test was estimated to be 2
      TCID50/50 MUL. The analysis of tissue homogenate samples from naturally infected
      animals proved the potential usefulness of the method for a rapid disease
      diagnosis from field cases. 

PMID- 24031452
TI  - The contribution of genes required for anaerobic respiration to the virulence of
      Salmonella enterica serovar Gallinarum for chickens.
AB  - Salmonella enterica serovar Gallinarum (SG) is an intracellular pathogen of
      chickens. To survive, to invade and to multiply in the intestinal tract and
      intracellularly it depends on its ability to produce energy in anaerobic
      conditions. The fumarate reductase (frdABCD), dimethyl sulfoxide (DMSO)
      trimethylamine N-oxide (TMAO) reductase (dmsABC), and nitrate reductase (narGHIJ)
      operons in Salmonella Typhimurium (STM) encode enzymes involved in anaerobic
      respiration to the electron acceptors fumarate, DMSO, TMAO, and nitrate,
      respectively. They are regulated in response to nitrate and oxygen availability
      and changes in cell growth rate. In this study mortality rates of chickens
      challenged with mutants of Salmonella Gallinarum, which were defective in
      utilising anaerobic electron acceptors, were assessed in comparison to group of
      bird challenged with wild strain. The greatest degree of attenuation was observed
      with mutations affecting nitrate reductase (napA, narG) with additional
      attenuations induced by a mutation affecting fumarate reductase (frdA) and a
      double mutant (dmsA torC) affecting DMSO and TMAO reductase. 

PMID- 24031453
TI  - Increased presevation of sliced mozzarella cheese by antimibrobial sachet
      incorporated with allyl isothiocyanate.
AB  - There is an increasing tendency to add natural antimicrobials of plant origin
      into food. The objective of this work was to develop a microbial sachet
      incorporated with allyl isothiocyanate (AIT), a volatile compound of plant
      origin, and to test its efficiency against growth of yeasts and molds,
      Staphylococcus sp. and psychrotrophic bacteria on sliced mozzarella cheese.
      Another objective was to quantify the concentration of AIT in the headspace of
      cheese packaging. A reduction of 3.6 log cycles was observed in yeasts and molds
      counts in the mozzarella packed with the antimicrobial sachet over 15-day storage
      time. The sachet also showed an antibacterial effect on Staphylococcus sp.,
      reducing 2.4 log cycles after 12-day storage. Psychrotrophic bacteria species
      were the most resistant to the antimicrobial action. The highest concentration of
      AIT (0.08ug.mL(-1)) inside the active packaging system was observed at the 6(
      )day of storage at 12 oC +/- 2 oC. At the end of the storage time, AIT
      concentration decreased to only 10% of the initial concentration. Active
      packaging containing antimicrobial sachet has a potential use for sliced
      mozzarella, with molds and yeasts being the most sensitive to the antimicrobial
      effects. 

PMID- 24031454
TI  - Antimicrobial susceptibility of Streptococcus pneumoniae and genotypic
      characterization of erythromycin-resistant strains in porto alegre, Brazil.
AB  - The antimicrobial susceptibility of 64 strains of S. pneumoniae obtained from
      three hospitals in Porto Alegre, Brazil, isolated between 2004 and 2005. was
      determined, using the agar-dilution method. The prevalence of resistant
      (intermediate and full resistance) strains to trimethoprim/sulphamethoxazole,
      penicillin, tetracycline, erythromycin, chloramphenicol, and ceftriaxone were
      68%, 28%, 18%, 15%, 3%, and 1%, respectively. All strains were susceptible to
      vancomycin. Among 18 penicillin-resistant strains, 7 were resistant to at least
      two other antimicrobial drugs. All erythromycin-resistant strains, except one,
      contained the erm(B) and/or mef(A/E) genes, with a predominance of the former.
      The resistance rate to penicillin and erythromycin in Porto Alegre remained
      stable. The combination of trimethoprim/ sulphamethoxazole should not be
      recommended to treat pneumococcal infections, because of the high rate of
      resistant strains. 

PMID- 24031455
TI  - Vaginal lactobacilli as potential probiotics against Candida SPP.
AB  - Urogenital infections affect millions of people every year worldwide. The
      treatment of these diseases usually requires the use of antimicrobial agents, and
      more recently, the use of probiotic lactic acid bacteria (LAB) cultures for the
      management of vaginal infections has been extensively studied. In this work, 11
      vaginal lactobacilli isolates, previously obtained from healthy patients, were
      studied to screen microorganisms with probiotic properties against Candida spp.
      The LAB were tested for their ability of auto-aggregation, co-aggregation with C.
      albicans, C. glabrata, C. krusei, and C. tropicalis, adhesion to Caco-2
      epithelial cells and production of lactic acid and hydrogen peroxide (H2O2). All
      lactobacilli isolates tested were able to auto-aggregate (ranging from 25.3% to
      75.4% assessed at 4 hours of incubation) and to co-aggregate with the four
      Candida species into different degrees; among them L. crispatus showed the
      highest scores of co-aggregation. The highest amount of lactic acid was produced
      by L. salivarius (13.9 g/l), followed by L. johnsonii (6.5 g/l), L. acidophilus
      (5.5 g/l), and L. jensenii (5.4 g/l). All isolates produced H2O2, but the highest
      levels (3 - 10 mg/l) were observed for L. acidophilus, L. crispatus, L. gasseri,
      L. johnsonii, and L. vaginalis. Only L. agilis, L. jensenii, L. johnsonii and L.
      ruminus were able to adhere to epithelial Caco-2 cells. Among the isolates
      evaluated, L agilis, L. jensenii, L. johnsonii, and L. ruminus exhibited
      simultaneously several desirable properties as potential probiotic strains
      justifying future studies to evaluate their technological properties in different
      pharmaceutical preparations for human use. 

PMID- 24031456
TI  - Enumeration of heterotrophic bacteria in water for dialysis: Comparison of the
      efficiency of reasoner'2 agar and plate count agar.
AB  - Due to the fact the incubation conditions may influence the microbiological
      evaluation of water for dialysis, the objective of the present study was the
      comparison of the efficiency of R2A and PCA media in the enumeration of
      heterotrophic bacteria in 193 samples of water collected in dialysis clinics from
      12 cities in Sao Paulo, between October and December 2007. Results showed counts
      significantly greater in R2A, suggesting that enumeration should be carried out
      in R2A, suggesting that enumeration should be carried out in R2A agar associated
      with longer incubation times, because of the greater sensitivity. 

PMID- 24031457
TI  - Epidemiology and phospholipase activity of oral Candida SPP. Among patients with
      central nervous system diseases before and after dental cleaning procedure.
AB  - Patients suffering of diseases that affect central nervous system may be
      considered more susceptible to the infectious diseases of mouth. Sixty-nine
      patients suffering of cerebral palsy, Down's syndrome and metal retardation were
      submitted to saliva examination for the presence of Candida spp. before and after
      a procedure of dental cleaning. The isolates were submitted to assay for
      verifying phospholipase production. 55.10% of the patients provided isolation of
      Candida spp. The frequency of isolation obtained before dental procedure was: C.
      albicans (83.33%), C. krusei (8.33%) and C. kefyr, C. parapsilosis and C.
      glabrata (2.78% each). The frequency after the procedure was: C. albicans
      (68.57%), C. parapsilosis (11.43%), C. krusei and C. kefyr (8.57% each) and
      Candida glabrata (2.86%). We verified significantly difference (p < 0.01) between
      populations obtained at the two examinations. Phospholipase production was
      verified only among C. albicans strains and the proportion of producers was
      higher when testing isolates obtained after dental cleaning procedure. Studies
      focused on Candida spp. isolation are useful for better comprehension of the role
      of these yeasts on the oral flora from patients with cerebral palsy, Down's
      syndrome and metal retardation. 

PMID- 24031458
TI  - Nasopharyngeal Gram-Negative bacilli colonization in brazilian children attending
      day-care centers.
AB  - This study aimed at determining prevalence and resistance profile of Gram
      negative bacilli isolated from nasopharynx of children attending day-care centers
      in Goiania (Brazil). P. aeruginosa (100.0%), E. coli (50.0%), K. pneumoniae
      (35.3%), and E. aerogenes (16.7%) were the most frequent multi-drug resistant
      microorganisms isolated. No production of ESBL was detected. 

PMID- 24031459
TI  - Chemical composition and antifungal activity of Hyptis Suaveolens (L.) Poit
      leaves essential oil against Aspergillus species.
AB  - This study aimed to identify the constituents of the essential oil from Hyptis
      suaveolens (L.) leaves using a Gas Chromatograph - Mass Spectrometer and assess
      its inhibitory effect on some potentially pathogenic Aspergilli (A. flavus, A.
      parasiticus, A. ochraceus, A. fumigatus and A. niger). Eucaliptol (47.64 %) was
      the most abundant component in the oil, followed for gama-ellemene (8.15 %), beta
      pynene (6.55 %), (+)-3-carene (5.16 %), trans-beta-cariophyllene (4.69 %) and
      germacrene (4.86 %). The essential oil revealed an interesting anti-Aspergillus
      property characterized by a Minimum Inhibitory Concentration and Minimum
      Fungicidal Concentration of 40 and 80 uL/mL, respectively. The oil at 80 and 40
      uL/mL strongly inhibited the mycelial growth of A. fumigatus and A. parasiticus
      along 14 days. In addition, at 10 and 20 uL/mL the oil was able to cause
      morphological changes in A. flavus as decreased conidiation, leakage of
      cytoplasm, loss of pigmentation and disrupted cell structure suggesting fungal
      wall degeneration. These findings showed the interesting anti-Aspergillus
      property of H. suaveolens leaves essential oil supporting its possible rational
      use as alternative source of new antifungal compounds to be applied in the
      aspergillosis treatment. 

PMID- 24031460
TI  - First report of vancomycin-resistant enterococcus faecalis in Uberaba, Minas
      gerais state.
AB  - In this study we report the first isolation of VanA-type vancomycin-resistant
      Enterococcus faecalis strains from two different patients hospitalized in the
      same intensive care unit at the hospital of Universidade Federal do Triangulo
      Mineiro (UFTM), Uberaba, Minas Gerais, Brazil. 

PMID- 24031461
TI  - Iron-Depletion prevents biofilm formation in Pseudomonas Aeruginosa through
      twitching mobility and quorum sensing.
AB  - Influence of iron-depletion on twitching motility and quorum sensing (QS) system
      in P. aeruginosa was evaluated. The results demonstrated iron-depletion can
      retard biofilm formation and increase the twitching motility and expression of QS
      related genes, suggesting a potential interaction between twitching motility and
      QS system in P. aeruginosa biofilm formation. 

PMID- 24031462
TI  - Photodynamic inactivation of four Candida species induced by photogem((r)).
AB  - This study evaluated the in vitro susceptibility of C. albicans, C. dubliniensis,
      C. tropicalis and C. krusei to photodynamic therapy (PDT) induced by
      Photogem((r))and light emitted diode (LED). Suspensions of each Candida strain
      were treated with three photosensitizer (PS) concentrations (10, 25 and 50 mg/L)
      and exposed to 18, 25.5 and 37.5 J/cm(2) LED light fluences (lambda ~ 455 nm).
      Control suspensions were treated only with PS concentrations, only exposed to the
      LED light fluences or not exposed to LED light or PS. Sixteen experimental
      conditions were obtained and each condition was repeated three times. From each
      sample, serial dilutions were obtained and aliquots were plated on Sabouraud
      Dextrose Agar. After incubation of plates (37  degrees C for 48 hours), colonies
      were counted (cfu/mL) and the data were statistically analyzed by ANOVA and the
      Tukey test (alpha=0.05). Complete killing of C. albicans was observed after 18
      J/cm(2) in association with 50 mg/L of PS. C. dubliniensis were inactivated after
      18 J/cm(2) using 25 mg/L of PS. The inactivation of C. tropicalis was observed
      after photosensitization with 25 mg/L and subsequent illumination at 25.5
      J/cm(2). For C. krusei, none of the associations between PS and light resulted in
      complete killing of this species. PDT proved to be effective for the inactivation
      of C. albicans, C. dubliniensis and C. tropicalis. In addition, reduction in the
      viability of C. krusei was achieved with some of the PS and light associations. 

PMID- 24031463
TI  - Active human cytomegalovirus infection and glycoprotein b genotypes in brazilian
      pediatric renal or hematopoietic stem cell transplantation patients.
AB  - A prospective analysis of active Human Cytomegalovirus infection (HCMV) was
      conducted on 33 pediatric renal or hematopoietic stem cell post-transplant
      patients. The HCMV-DNA positive samples were evaluated for the prevalence of
      different gB subtypes and their subsequent correlation with clinical signs. The
      surveillance of HCMV active infection was based on the monitoring of antigenemia
      (AGM) and on a nested polymerase chain reaction (N-PCR) for the detection of HCMV
      in the patients studied. Using restriction analysis of the gB gene sequence by
      PCR-RFLP (Restriction Fragment Length Polymorphism), different HCMV strains could
      be detected and classified in at least four HCMV genotypes. Thirty-three
      pediatric recipients of renal or bone marrow transplantation were monitored.
      Twenty out of thirty-three (60.6%) patients demonstrated active HCMV infection.
      gB1 and gB2 genotypes were more frequent in this population. In this study, we
      observed that gB2 had correlation with reactivation of HCMV infection and that
      patients with mixture of genotypes did not show any symptoms of HCMV disease.
      Future studies has been made to confirm this. 

PMID- 24031464
TI  - Detection of enterotoxin genes of Staphylococcus SP isolated from nasal cavities
      and hands of food handlers.
AB  - Food handlers, an important factor in food quality, may contain bacteria that are
      able to cause foodborne disease. The present study aimed to research coagulase
      negative (CNS) and -positive staphylococci (CPS) in 82 food handlers, analyzing
      nasal and hand swabs, with identification of 62 CNS (75.6%) and 20 CPS strains
      (24.4%). Staphylococcal enterotoxins genes were investigated by PCR. In 20 CPS
      strains, 19 were positive for one or more genes. The percentage of CNS presenting
      genes for enterotoxins was high (46.8%). Despite of the staphylococcal species,
      the most common gene was sea (35.4%), followed by seh and sej (29.2%). The
      detection of new staphylococcal enterotoxins (SEs) genes showed a higher
      pathogenic potential in this genus. The presence of these gene points out the
      importance of CNS not only as contaminant bacteria but also as a pathogen. 

PMID- 24031465
TI  - Control of Colletotrichum gloeosporioides (penz.) Sacc. In yellow passion fruit
      using Cymbopogon citratus essential oil.
AB  - The use of antibiotics in agriculture is limited when compared to their
      applications in human and veterinary medicine. On the other hand, the use of
      antimicrobials in agriculture contributes to the drug resistance of human
      pathogens and has stimulated the search for new antibiotics from natural
      products. Essential oils have been shown to exert several biological activities
      including antibacterial and antifungal actions. The aim of this study was to
      determine the activity of 28 essential oils from medicinal plants cultivated at
      CPMA (Medicinal and Aromatic Plants Collection), CPQBA/UNICAMP, against
      Colletotrichum gloeosporioides (Penz.) Sacc., the anthracnose agent in yellow
      passion fruit (Passiflora edulis Sims f. flavicarpa Deg), as well as evaluating
      their effect in the control of post-harvest decay. The oils were obtained by
      water-distillation using a Clevenger-type system and their minimal inhibitory
      concentrations (MIC) determined by the micro-dilution method. According to the
      results, 15 of the 28 essential oils presented activity against Colletotrichum
      gloeosporioides, and the following four oils presented MIC values between 0.25
      and 0.3 mg/mL: Coriandrum sativum, Cymbopogon citratus, Cymbopogon flexuosus and
      Lippia alba. The evaluation of Cymbopogon citratus essential oil in the control
      of post-harvest decay in yellow passion fruit showed that the disease index of
      the samples treated with the essential oil did not differ (P <= 0.05) from that
      of the samples treated with fungicide. The present study shows the potential of
      Cymbopogon citratus essential oil in the control of the anthracnose agent in
      yellow passion fruit. 

PMID- 24031466
TI  - Antimicrobial activity of Enterococcus Faecium Fair-E 198 against gram-positive
      pathogens.
AB  - This study investigated the antimicrobial activity of Enterococcus faecium FAIR-E
      198 against Bacillus cereus, Listeria monocytogenes and Staphylococcus aureus.
      Using the critical-dilution method, the bacteriocin produced by E. faecium FAIR-E
      198 inhibited all L. monocytogenes strains evaluated (1,600 to 19,200 AU mL(-1)).
      However, none of the B. cereus and S. aureus strains investigated were inhibited.
      The maximum activity of this bacteriocin (800 AU mL(-1)) was observed in MRS
      broth, while the activity in milk was 100 AU mL(-1). In the co-cultivation test
      in milk, B. cereus K1-B041 was reduced to below the detection limit (1.00 log CFU
      mL(-1)) after 48 h. E. faecium reduced the initial L. monocytogenes Scott A
      population by 1 log CFU mL(-1) after 3 h at 35 degrees C, However, the pathogen
      regained growth, reaching 3.68 log CFU mL(-1) after 48 h. E. faecium did not
      influence the growth of S. aureus ATCC 27154 during the 48 h of co-cultivation,
      Therefore, it can be concluded that the effectiveness of the antimicrobial
      activity of E. faecium FAIR-E 198 is strictly related to the species and strain
      of the target microorganism and to the culture medium. 

PMID- 24031467
TI  - Immobilized Saccharomyces Cerevisiae as a potential aflatoxin decontaminating
      agent in pistachio nuts.
AB  - In this study, we investigated the binding ability of Saccharomayces cerevisiae
      to aflatoxin in pistachio nuts. The obtained results indicate that S. cerevisiae
      has an aflatoxin surface binding ability of 40% and 70% (with initial aflatoxin
      concentrations of 10 and 20 ppb) in the exponential phase. Acid treatments
      increase this ability to approximately 60% and 73% for the two concentrations of
      aflatoxin, respectively. Heat treatments also enhance surface binding to 55% and
      75%, respectively. Binding appears to be a physical phenomenon that saturates
      within the first 2-3 hours of the process. The obtained results indicate that
      yeast immobilization for toxin reduction on aflatoxin-contaminated pistachios had
      no effect on qualitative characteristics, such as color, texture, and peroxide
      value. Yeast cells, viable or nonviable, are effective for aflatoxin binding, and
      this property could lead to a promising solution to aflatoxin contamination in
      high-risk foods. 

PMID- 24031468
TI  - The proteolytic activity of Pseudomonas Fluorescens 07A isolated from milk is not
      regulated by quorum sensing signals.
AB  - The proteolytic activity of Pseudomonas fluorescens 07A was investigated, and was
      optimal on tryptone-calcium medium. N-acyl-homoserine lactones (AHLs) were not
      detected on supernatants of late-exponential and stationary-phase culture broths.
      Synthetic AHLs or bacterial cell extracts added to the medium did not influence
      growth or proteolytic activity suggesting that quorum sensing might not regulate
      protease production in this strain. 

PMID- 24031469
TI  - Biofilm formation by Listeria monocytogenes on stainless steel surface and
      biotransfer potential.
AB  - An experimental model was proposed to study biofilm formation by Listeria
      monocytogenes ATCC 19117 on AISI 304 (#4) stainless steel surface and biotransfer
      potential during this process. In this model, biofilm formation was conducted on
      the surface of stainless steel coupons, set on a stainless steel base with 4
      divisions, each one supporting 21 coupons. Trypic Soy Broth was used as bacterial
      growth substrate, with incubation at 37  degrees C and stirring of 50 rpm. The
      number of adhered cells was determined after 3, 48, 96, 144, 192 and 240 hours of
      biofilm formation and biotransfer potential from 96 hours. Stainless steel
      coupons were submitted to Scanning Electron Microscopy (SEM) after 3, 144 and 240
      hours. Based on the number of adhered cells and SEM, it was observed that L.
      monocytogenes adhered rapidly to the stainless steel surface, with mature biofilm
      being formed after 240 hours. The biotransfer potential of bacterium to substrate
      occurred at all the stages analyzed. The rapid capacity of adhesion to surface,
      combined with biotransfer potential throughout the biofilm formation stages, make
      L. monocytogenes a potential risk to the food industry. Both the experimental
      model developed and the methodology used were efficient in the study of biofilm
      formation by L. monocytogenes on stainless steel surface and biotransfer
      potential. 

PMID- 24031470
TI  - USE of pseudomonas stutzeri and candida utilis in the improvement of the
      conditions of artemia culture and protection against pathogens.
AB  - To evaluate the effect of two bacterial strains isolated from Artemia cysts and
      yeast (Candida utilis) on the survival, growth and total biomass production of
      its larvae, challenge tests were performed with Candida utilis, Pseudomonas
      stutzeri and Pasteurella haemolityca. In addition, a pathogenic strain of Vibrio
      alginolyticus was tested for comparative purposes. Pseudomonas stutzeri and
      Candida utilis have no impact on survival, but enhance growth and total biomass
      production of the larvae. However, we noted that Pasteurella haemolityca affect
      negatively Artemia larvae. The adhesion and antagonism assay demonstrates that
      Candida utilis and Pseudomonas stutzeri are fairly adherent and play an important
      role in the enhancement of the protection of Artemia culture against pathogens.
      On the basis of these results, it's suggested that it's possible to use Candida
      utilis and Pseudomonas stutzeri, potential candidates, as probiotic for the
      culture of Artemia larvae. 

PMID- 24031471
TI  - In vitro activity of origanum vulgare essential oil against candida species.
AB  - The aim of this study was to evaluate the in vitro activity of the essential oil
      extracted from Origanum vulgare against sixteen Candida species isolates.
      Standard strains tested comprised C. albicans (ATCC strains 44858, 4053, 18804
      and 3691), C. parapsilosis (ATCC 22019), C. krusei (ATCC 34135), C. lusitaniae
      (ATCC 34449) and C. dubliniensis (ATCC MY646). Six Candida albicans isolates from
      the vaginal mucous membrane of female dogs, one isolate from the cutaneous
      tegument of a dog and one isolate of a capuchin monkey were tested in parallel. A
      broth microdilution technique (CLSI) was used, and the inoculum concentration was
      adjusted to 5 x 10(6) CFU mL(-1). The essential oil was obtained by
      hydrodistillation in a Clevenger apparatus and analyzed by gas chromatography.
      Susceptibility was expressed as Minimal Inhibitory Concentration (MIC) and
      Minimal Fungicidal Concentration (MFC). All isolates tested in vitro were
      sensitive to O. vulgare essential oil. The chromatographic analysis revealed that
      the main compounds present in the essential oil were 4-terpineol (47.95%),
      carvacrol (9.42%), thymol (8.42%) and ?-terpineol (7.57%). C. albicans isolates
      obtained from animal mucous membranes exhibited MIC and MFC values of 2.72 MUL
      mL(-1) and 5 MUL mL(-1), respectively. MIC and MFC values for C. albicans
      standard strains were 2.97 MUL mL(-1) and 3.54 MUL mL(-1), respectively. The MIC
      and MFC for non-albicans species were 2.10 MUL mL(-1) and 2.97 MUL mL(-1),
      respectively. The antifungal activity of O. vulgare essential oil against Candida
      spp. observed in vitro suggests its administration may represent an alternative
      treatment for candidiasis. 

PMID- 24031472
TI  - Selection and characterization of brivudin resistant bovine herpesvirus type 5.
AB  - Bovine herpesvirus type 5 (BoHV-5) is the agent of meningoencephalitis, an
      important disease of cattle in South America. The neuropathogenesis of BoHV-5
      infection is poorly understood and most previous research focused on the role of
      envelope glicoproteins in neurovirulence. Thymidine kinase (TK) is a viral enzyme
      necessary for virus replication in neurons and, therefore, represents a potential
      target for virus attenuation. The selection and characterization of BoHV-5
      variants resistant to the nucleoside analog brivudin (BVDU), which selects TK
      defective viruses is here described. Several BVDU-resistant clones were obtained
      after multiple passages in tissue culture in the presence of BVDU and one clone
      (BoHV-5/R-27) was further characterized. The selected clone replicated to similar
      titers and produced plaques with similar size and morphology to those of wild
      type virus (SV507/99). The genetic stability of the resistant virus was
      demonstrated after ten passages in cell culture in the absence of the drug.
      Moreover, the drug-resistant virus showed reduced virulence in a rabbit model:
      virus inoculation in four rabbits did not result in disease, in contrast with 75%
      morbidity (3/4) and 50% mortality (2/2) among rabbits inoculated with the
      parental virus. These results demonstrate that BoHV-5 is sensitive to BVDU and
      that drug-resistant mutants can be readily selected upon BVDU treatment. BVDU
      resistant mutants, likely defective in TK, retained their ability to replicate in
      tissue culture yet were attenuated for rabbits. This strategy to obtain TK
      defective BoHV-5 may be useful to study the role of TK in BoHV-5
      neuropathogenesis and for vaccine development. 

PMID- 24031473
TI  - Mode of action and In Vitro susceptibility of mastitis pathogens to macedocin
      ST91KM and preparation of a teat seal containing the bacteriocin.
AB  - Mastitis is considered to be the most economically costly disease affecting the
      dairy industry. Regular dosage of animals with antibiotics, including use of
      prophylactic concentrations, may select for resistant strains. The purpose of
      this study was to determine the mode of action of a new bacteriocin (macedocin
      ST91KM), to evaluate the antimicrobial resistance of mastitis pathogens to
      antibiotics commonly used in treatment remedies, and to introduce the possible
      use of an alternative antimicrobial agent. The bacteriocin macedocin ST91KM,
      produced by Streptococcus gallolyticus subsp. macedonicus ST91KM, is bactericidal
      to Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis and
      Staphylococcus aureus associated with mastitis infections, including strains
      resistant to methicillin and oxacillin. Sensitive cells were deformed and
      secreted nucleotides, K(+) and beta-galactosidase when exposed to macedocin
      ST91KM. Adsorption of the peptide to target cells decreased in the presence of
      solvents, suggesting that receptors on the cell surfaces have lipid moieties. No
      adsorption was recorded in the presence of MgCl2, KI and Na2CO3, suggesting that
      ionic strength plays an important role. A teat seal preparation containing
      macedocin ST91KM effectively released the peptide and inhibited the growth of S.
      agalactiae. Macedocin ST91KM could form the basis for alternative dry cow therapy
      to prevent mastitis infections in dairy cows as it is effective against pathogens
      that display resistance to conventional antibiotic therapy. 

PMID- 24031474
TI  - Glanders in donkeys (Equus Asinus) in the state of pernambuco, Brazil: A case
      report.
AB  - The clinical, anatomical and histopatological findings of glanders diagnosis in
      donkeys in the state of Pernambuco-Brazil are reported. The animals were
      euthanized and necropsied, and evaluated for lesions in respiratory and lymphatic
      systems, confirming the disease by isolation of Burkholderia mallei and Strauss
      test. 

PMID- 24031475
TI  - Characterization of leptospira borgpetersenii isolates from field rats (rattus
      norvegicus) by 16s rrna and lipl32 gene sequencing.
AB  - The main goal of this study was to evaluate the prevalence of leptospirosis among
      field rodents of Tiruchirappalli district, Tamil Nadu, India. In total 35 field
      rats were trapped and tested for seroprevalence by the microscopic agglutination
      test (MAT). Isolation of leptospires was performed from blood and kidney tissues
      and characterized to serovar level. Genomospecies identification was carried out
      using 16S rRNA and lipL32 gene sequencing. The molecular phylogeny was
      constructed to find out species segregation. Seroprevalence was about 51.4 %, and
      the predominant serovars were Autumnalis, Javanica, Icterohaemorrhagiae and
      Pomona. Two isolates from the kidneys were identified as serovar Javanica of
      Serogroup Javanica, and sequence based molecular phylogeny indicated these two
      isolates were Leptospira borgpetersenii. 

PMID- 24031476
TI  - Antibacterial activity, chemical composition, and cytotoxicity of leaf's
      essential oil from brazilian pepper tree (schinus terebinthifolius, raddi).
AB  - The antibacterial potential of leaf's essential oil (EO) from Brazilian pepper
      tree (Schinus terebinthifolius Raddi) against staphylococcal isolates from dogs
      with otitis externa was evaluated. The minimum inhibitory concentration of EO
      ranged from 78.1 to 1,250 MUg/mL. The oil was analyzed by GC and GC/MS and
      cytotoxicity tests were carried out with laboratory animals. 

PMID- 24031477
TI  - Response surface methodology for optimization of production of lovastatin by
      solid state fermentation.
AB  - Lovastatin, an inhibitor of HMG-CoA reductase, was produced by solid state
      fermentation (SSF) using a strain of Aspergillus terreus UV 1718. Different solid
      substrates and various combinations thereof were evaluated for lovastatin
      production. Wheat bran supported the maximum production (1458 +/- 46 ug g(-1)
      DFM) of lovastatin. Response surface methodology (RSM) was applied to optimize
      the medium constituents. A 2(4) full-factorial central composite design (CCD) was
      chosen to explain the combined effects of the four medium constituents, viz.
      moisture content, particle size of the substrate, di -potassium hydrogen
      phosphate and trace ion solution concentration. Maximum lovastatin production of
      2969 ug g(-1) DFM was predicted by the quadratic model which was verified
      experimentally to be 3004 +/- 25 MUg g(-1) DFM. Further RSM optimized medium
      supplemented with mycological, peptone supported highest yield of 3723.4+/-49 ug
      g(-1) DFM. Yield of lovastatin increased to 2.5 fold as with compared to un
      optimized media. 

PMID- 24031478
TI  - Production, purification and characterization of l-asparaginase from streptomyces
      gulbargensis.
AB  - L-asparaginase is an anti-neoplastic agent used in the lymphoblastic leukaemia
      chemotherapy. In the present study a novel strain, Streptomyces gulbargensis was
      explored for the production of extra-cellular L-asparaginase using groundnut cake
      extract. The optimum pH, temperature, inoculum size and agitation speed for
      enzyme production were pH 8.5, 40 degrees C, 1x10(8)spores/ml and 200 rev/min
      respectively. Maltose (0.5%) and L-asparagine (0.5%) proved to be the best carbon
      and nitrogen sources respectively. The enzyme was purified 82.12 fold and the
      apparent molecular weight of the enzyme was found to be 85 kDa. The optima pH and
      temperature for the enzyme were 9.0 and 40 degrees C respectively. The enzyme was
      more stable at the alkaline pH than at the acidic one and it retained 55% of the
      activity at 80 degrees C for 60 min. 

PMID- 24031479
TI  - Concomitant production of protease and lipase by Bacillus Licheniformis VSG1:
      Production, purification and characterization.
AB  - This study was aimed at producing protease and lipase simultaneously on a common
      medium by Bacillus licheniformis VSG1, which was isolated from a tannery
      effluent. The effect of media composition with respect to protein source, lipid
      source and emulsifier on the production of protease and lipase was analysed. Both
      those enzymes were produced under optimized conditions like pH, temperature and
      incubation time. The enzyme mixture comprising of both protease and lipase was
      purified by ammonium sulphate precipitation, dialysis and gel filtration
      chromatography to obtain 20-fold pure enzymes. The purified enzyme mixture was
      characterized to determine the optimum pH and temperature of protease and lipase,
      the response of the enzymes to inhibitors, additives and solvents. The molecular
      weight of both the enzymes was determined as 40 kDa on SDS-PAGE. The concomitant
      production of protease and lipase and the purification of both the enzymes in a
      single mixture have industrial significance, as many industrial processes use
      both protease and lipase together. 

PMID- 24031480
TI  - Mutagenesis of Aspergillus Oryzae IPT-301 to improve the production of beta
      Fructofuranosidase.
AB  - Aspergillus oryzae IPT-301, previously reported as a beta-fructofuranosidase
      producing microorganism, was successfully mutated using UV irradiation at 253.7
      nm followed by the screening of survivors resistant to certain stress conditions.
      Strains were first subjected to the beta-fructofuranosidase activity assay using
      a portion from the colony grown in Petri dish as the enzyme source. Seven mutants
      with beta-fructofuranosidase activity values relative to the parent culture
      between 140 - 190% were selected from survivors grown at temperature of 40oC or
      0.018% (w/v) sodium dodecyl sulfate concentration. They were cultivated on a
      rotary shaker to characterize mycelium and extracellular fructosyltransferase
      activities. Three mutants named IPT-745, IPT-746 and IPT-748 showed the highest
      amount of mycelium activity whose values increased 1.5 - 1.8 fold, compared with
      the parent strain. It was found that more than 55% of total enzyme activity
      (mycelium- plus extracellular- activity) from these strains was detected in the
      mycelium fraction. Only one mutant, IPT-747, exceeded the amount of extracellular
      enzyme exhibited by the parent strain (1.5 times). This mutant also showed the
      highest value of total fructosyltransferase activity. 

PMID- 24031481
TI  - Feather degradation by strains of Bacillus isolated from decomposing feathers.
AB  - Feather waste is generated in large amounts as a by-product of commercial poultry
      processing. This residue is almost pure keratin, which is not easily degradable
      by common proteolytic enzymes. Eight strains of Bacillus, isolated from
      decomposing feathers were tested for the hydrolysis of feather wastes in the
      laboratory. Among these strains, Bacillus cereus KB043 was the best feather
      degrading organism when grown on basal medium containing 1% hen feather as sole
      source of carbon and nitrogen. It caused 78.16 +/- 0.4 % degradation with a
      significant release of soluble protein (1206.15 +/- 14.7 ug mL(-1)) and cysteine
      (20.63 +/- 0.4 ug mL(-1)) in the cultivation fluid. The strain also showed the
      highest level of keratinase activity (39.10 +/- 0.4 U mL(-1)). These data
      indicates that the Bacillus cereus KB043 could be useful in management of poultry
      wastes. 

PMID- 24031482
TI  - Characterization of indigenous rhizobia from caatinga.
AB  - The aim of this study was to characterize rhizobial isolates from Cratylia mollis
      Mart. ex Benth, Calliandra depauperata Benth. and Mimosa tenuiflora (Willd.)
      Poir. by means of rhizobial colonies morphology and restriction analysis of the
      16S ribosomal gene (16S rDNA-ARDRA). Nodules were collected in the field and from
      plants cultivated in a greenhouse experiment using Caatinga soil samples. Sixty
      seven isolates were described by morphological analysis. Forty seven
      representative isolates were used for ARDRA analysis using seven restriction
      enzymes. We observed high diversity of both slow and fast-growing rhizobia that
      formed three morpho-physiological clusters. A few fast-growing isolates formed a
      group of strains of the Bradyrhizobium type; however, most of them diverged from
      the B. japonicum and B. elkanii species. Cratylia mollis nodule isolates were the
      most diverse, while all Mimosa tenuiflora isolates displayed fast growth with no
      pH change and were clustered into groups bearing 100% similarity, according to
      ARDRA results. 

PMID- 24031483
TI  - Microbial degradation of sulfentrazone in a Brazilian rhodic hapludox soil.
AB  - Sulfentrazone is amongst the most widely used herbicides for treating the main
      crops in the State of Sao Paulo, Brazil, but few studies are available on the
      biotransformation of this compound in Brazilian soils. Soil samples of Rhodic
      Hapludox soil were supplemented with sulfentrazone (0.7 ug active ingredient
      (a.i.) g(-1) soil) and maintained at 27 degrees C. The soil moisture content was
      corrected to 30, 70 or 100 % water holding capacity (WHC) and maintained constant
      until the end of the experimental period. Herbicide-free soil samples were used
      as controls. Another experiment was carried out using soil samples maintained at
      a constant moisture content of 70% WHC, supplemented or otherwise with the
      herbicide, and submitted to different temperatures of 15, 30 and 40 degrees  C.
      In both experiments, aliquots were removed after various incubation periods for
      the quantitative analysis of sulfentrazone residues by gas chromatography.
      Herbicide-degrading microorganisms were isolated and identified. After 120 days a
      significant effect on herbicide degradation was observed for the factor of
      temperature, degradation being higher at 30 and 40 degrees  C. A half-life of
      91.6 days was estimated at 27 degrees  C and 70 % WHC. The soil moisture content
      did not significantly affect sulfentrazone degradation and the microorganisms
      identified as potential sulfentrazone degraders were Nocardia brasiliensis and
      Penicillium sp. The present study enhanced the prospects for future studies on
      the bio-prospecting for microbial populations related to the degradation of
      sulfentrazone, and may also contribute to the development of strategies for the
      bioremediation of sulfentrazone-polluted soils. 

PMID- 24031484
TI  - Abundance and diversity of ammonia-oxidizing bacteria in relation to ammonium in
      a chinese shallow eutrophic urban lake.
AB  - The measures of most-probable-number and restriction fragment length polymorphism
      analysis were used to analyze the abundance and diversity of ammonia-oxidizing
      bacteria in sediment of a Chinese shallow eutrophic urban lake (Lake Yuehu).
      Among the 5 sampling sites, ammonia concentration in interstitial water was
      positively proportional not only to the content of organic matter, but also to
      ammonia-oxidizing bacteria numbers (at a magnitude of 10(5) cells g(-1) dry
      weight) in sediment significantly. Furthermore, the diversity of ammonia
      oxidizing bacteria were determined by means of PCR primers targeting the amoA
      gene with five gene libraries created and restriction pattern analysis. The 13
      restriction patterns were recorded with 4 ones being common among all sampling
      sites. The 8 restriction patterns including 4 unique ones were found at the site
      with the highest NH4 (+) concentrations in interstitial water, while, there were
      only common patterns without unique ones at the site with the lowest NH4 (+)
      concentrations in interstitial water. Phylogenetic analysis showed that the amoA
      fragments retrieved belong to Nitrosomonas oligotropha & ureae lineage, N.
      europaea lineage, N. communis lineage and Nitrosospira lineage, most of which
      were affiliated with the genus Nitrosomonas. The N. oligotropha & ureae-like
      bacteria were the dominant species. Thus, the abundance and diversity of sediment
      AOB is closely linked to ammonium status in eutrophic lakes. 

PMID- 24031485
TI  - 2(5H)-Furanone: A Prospective strategy for biofouling-control in membrane biofilm
      bacteria by quorum sensing inhibition.
AB  - Biofouling of membranes demands costly periodic cleaning and membrane
      replacement. A sustainable and environmentally friendly solution for maintenance
      is not available and would be of great interest for many purposes including
      economical. As complex biofilm formation by environmental strains is the major
      cause of biofouling and biofilm formation in most cases are controlled by N
      Acylhomoserine lactone (AHL)-mediated Quorum Sensing (QS). An effort was made to
      understand the appropriateness of 2(5H)-furanone, to use against biofouling of
      membranes. QS inhibition activity by 2(5H)-furanone was studied using
      bioindicator strains and known AHL of different acyl chain lengths. The biofilm
      inhibition was studied by growth analysis on polystyrene plate of Aeromonas
      hyrdrophila, an environmental biofilm strain isolated from a bio-fouled reverse
      osmosis (RO) membrane. Results showed a QS inhibition activity against a wide
      range of AHLs and also biofilm formation by 2(5H)-furanone, which is believed to
      act as a potential quorum inhibition agent in a bacterial biofilm community. 

PMID- 24031486
TI  - Bioemulsifier production byMicrobacterium SP. strains isolated from mangrove and
      their application to remove cadmiun and zinc from hazardous industrial residue.
AB  - The contamination of ecosystems with heavy metals is an important issue in
      current world and remediation technologies should be in according to
      environmental sustainability concept. Bioemulsifier are promising agents to be
      used in metal removal and could be effective to many applications in
      environmental industries. The aims of this work was screening the potential
      production of bioemulsifier by microorganisms isolated from an oil contaminated
      mangrove, and evaluate cadmium and zinc removal potential of those strains from a
      hazardous industrial residue. From that, bioemulsifier-producing bacteria were
      isolated from urban mangrove sediments. Four isolates were identified as
      Microbacterium sp by 16S rRNA analysis and were able to reduce up to 53.3% of
      culture medium surface tension (TS) when using glucose as carbon and energy
      source and 20.2% when sucrose was used. Suspensions containing bioemulsifier
      produced by Microbacterium sp. strains show to be able to remove cadmium and zinc
      from contaminated industrial residue, and its ability varied according carbon
      source. Significant differences in metal removal were observed by all strains
      depending on the carbon source. When glucose was used, Cd and Zn removal varied
      from 17 to 41%, and 14 to 68%, respectively. However, when sucrose was used it
      was observed only 4 to a maximum of 15% of Cd removal, and 4 to 17% of Zn
      removal. When the same tests were performed after ethanol precipitation, the
      results were different: the percentages of removal of Zn (7-27%) and Cd (14-32%)
      were higher from sucrose cultures. This is the first report of heavy metals
      removal by bioemulsifier from Microbacterium sp. 

PMID- 24031487
TI  - New hosts of Myrothecium SPP. In brazil and a preliminary In Vitro assay of
      fungicides.
AB  - Myrothecium roridum and M. verrucaria are two plant pathogenic species causing
      foliar spots in a large number of cultivated plants. This paper aims to study the
      causal agents of foliar spots in vegetable crops (sweet pepper, tomato,
      cucumber), ornamental plants (Spathiphyllum, Solidago canadensis, Anthurium,
      Dieffenbachia) and a solanaceous weed plant (Nicandra physalodes). Most of the
      isolates were identified as M. roridum; only the isolate 'Myr-02' from S.
      canadensis was identified as M. verrucaria. All the isolates were pathogenic to
      their original plant hosts and also to some other plants. Some fungicides were
      tested in vitro against an isolate of M. roridum and the mycelial growth recorded
      after seven days. Fungicides with quartenary ammonium, Tebuconzole and copper
      were highly effective in inhibiting the mycelial growth of M. roridum. This paper
      confirms the first record of M. roridum causing leaf spots in sweet pepper,
      tomato, Spathiphyllum, Anthurium, Dieffenbachia and N. physalodes. We also report
      M. roridum as causal agent of cucumber fruit rot and also M. verrucaria in tango
      plants. 

PMID- 24031488
TI  - Isolation and fusion of protoplasts from the phytopathogenic fungus sclerotium
      rolfsii(sacc.).
AB  - Sclerotium rolfsii (Sacc.) is a serious plant pathogenic fungus and lacks perfect
      (basidial) stage in production. Protoplast fusion technology was employed to
      reconstruct fusants from this fungus. Two strains designated as A and R were
      used. Maximum protoplast yields of 3.8x10(5)/g mycelia and 2.8x10(5)/g mycelia
      were formed in strains A and R respectively. Osmotic stabilizer sucrose 1M gave
      maximum yield. Lysing enzyme at the rate of 15mg/ml was found best for yield.
      Fusion of protoplasts from strains A and R was carried out in fusion media
      containing PEG 4000 30% (w/v) with 0.2mM CaCl2. Four fusants F1, F2, F3 and F4
      were recovered. Morphological, physiological and pathogenic characters of fusants
      were compared with parent strains on carrots, beans and tomato. 

PMID- 24031489
TI  - Cytological characterization of an Aspergillus Nidulans mutant from a strain with
      chromosomic duplication.
AB  - A development mutant, named V103, was obtained spontaneously from the A strain of
      A. nidulans. The A strain contains a duplicated segment of chromosome I that has
      undergone translocation to chromosome II (I II). It is mitotically unstable and
      generates phenotypically deteriorated types, some with enhanced stability. The
      deteriorated variants of A. nidulans show abnormal development, exhibiting slower
      colony growth, variations in colony pigmentation and changes in conidiophore
      structure. The alterations observed in the conidiophore include fewer metulae and
      phialides, further elongation and ramification of these structures, delayed
      nuclear migration and the presence of secondary conidiophores. 

PMID- 24031491
TI  - Prevalence of extended-spectrum beta-lactamases-producing microorganisms in
      nosocomial patients and molecular characterization of the shv type isolates.
AB  - The emergence of Extended-Spectrum Beta-Lactamase (ESBL)-producing microorganisms
      in Brazilian hospitals is a challenge that concerns scientists, clinicians and
      healthcare institutions due to the serious risk they pose to confined patients.
      The goal of this study was the detection of ESBL production by clinical strains
      of Escherichia coli and Klebsiella sp. isolated from pus, urine and blood of
      patients at Hospital Universitario Santa Maria, Rio Grande Sul, RS, Brazil and
      the genotyping of the isolates based on bla SHV genes. The ESBL study was carried
      out using the Combined Disc Method, while Polymerase Chain Reaction (PCR) was
      used to study the bla SHV genes. Of the 90 tested isolates, 55 (61.1%) were
      identified as ESBL-producing by the combined disk method. The bla SHV genes were
      found in 67.8% of these microorganisms. K. pneumoniae predominated in the
      samples, presenting the highest frequency of positive results from the combined
      disk and PCR. 

PMID- 24031490
TI  - Antimycobacterial susceptibility testing methods for natural products research.
AB  - The emergence of multidrug-resistant strains of Mycobacterium tuberculosis
      underscores the need of continuous developments on new and efficient methods to
      determine the susceptibility of isolates of M. tuberculosis in the search for
      novel antimicrobial agents. Natural products constitute an important source of
      new drugs, but design and implementation of antimycobacterial susceptibility
      testing methods are necessary for evaluate the different extracts and compounds.
      A number of biological assay methodologies are in current use, ranging from the
      classical disk diffusion and broth dilution assay format, to radiorespirometric
      (BACTEC), dye-based, and fluorescent/luminescence reporter assays. This review
      presents an analysis on the in vitro susceptibility testing methods developed for
      determinate antitubercular activity in natural products and related compounds
      (semi-synthetic natural products and natural products-derived compounds) and the
      criteria to select the adequate method for determination of biological activity
      of new natural products. 

PMID- 24031492
TI  - Yields from blood cultures of patients with suspected paratyphoid fever A.
AB  - The yield and speed of detection of Salmonella enterica serotype Paratyphi A from
      the blood of patients with suspected paratyphoid fever A in 13 500 paired aerobic
      and anaerobic bottles (AEB, ANB) that were each filled with 5 ml of blood by the
      BacT/ALERT 3D system were compared, and the blood bacterial counts of 1 000
      probable patients were estimated by pour plate method. A total of 4 060 isolates
      were recovered, of these, 3 149 were recovered from both AEB and ANB, 461 from
      the AEB only, and 450 from the ANB only. The estimating median bacterial count in
      blood from 400 patients was 0.5 CFU/ml. The research findings demonstrate that
      the blood volume drawn is an important factor determining the yields from blood
      cultures. Growth of significantly more isolates was detected earlier in AEB. 

PMID- 24031493
TI  - Identification of Candida spp. by phenotypic tests and PCR.
AB  - The correct identification of Candida species is of great importance, as it
      presents prognostic and therapeutical significance, allowing an early and
      appropriate antifungical therapy. The purpose of this study was to identify
      isolates of Candida spp. from oral mucosa of 38 patients with oral candidosis
      evaluated in 2004 by phenotypic methods and PCR, discriminating C. albicans from
      the other Candida species. The tests used for phenotypic analysis were germ-tube
      and chlamydoconidia production, culture in CHROMAgarTM Candida, carbohydrate
      assimilation test, growth at 45oC and culture in Tween 80 agar. Genotypic
      confirmation was performed by PCR. Phenotypic tests showed that 63.2% strains
      formed germ-tubes, 73.7% produced chlamydoconidia, and 63.2% showed green
      colonies in chromogenic medium, presumptively indicating C. albicans or C.
      dubliniensis. The carbohydrate assimilation test confirmed these results. A total
      of 21% strains were identified as C. krusei and 13.2% were indicative of C.
      tropicalis. Of these later strains, three produced chlamydoconidia. The
      association of other phenotypic tests with culture in Tween 80 agar identified
      95.8% of strains as C. albicans and 4.2% as C. dubliniensis. All 24 strains
      indicative of C. albicans and C. dubliniensis were confirmed by PCR as C.
      albicans. 

PMID- 24031494
TI  - A simple and rapid method of sample preparation from culture filtrate of M.
      tuberculosis for two-dimensional gel electrophoresis.
AB  - Sample preparation for Two-dimensional gel electrophoresis (2DE) is tedious and
      not sufficient to provide a comparative profile of secreted proteins for various
      strains of M. tuberculosis. High lipid content in mycobacteria limits the use of
      common methods as it can hinder the 2DE run. This study highlights the
      significance of SDS-TCA procedure over common used methods for the preparation of
      sample from culture filtrate as well as other proteinaceous fluids. 

PMID- 24031495
TI  - Growth kinetics of Mycobacterium tuberculosis measured by quantitative resazurin
      reduction assay: a tool for fitness studies.
AB  - We standardized a method to evaluate the growth kinetics of Mycobacterium
      tuberculosis by measuring quantitatively the reduction of resazurin by
      spectrophotometry. Growth curves and the rate of growth of twenty-one M.
      tuberculosis clinical isolates were determined. The method showed technical
      simplicity and is inexpensive to assess the fitness of each isolate. 

PMID- 24031496
TI  - Anti-Helicobacter pylori activity of plant extracts traditionally used for the
      treatment of gastrointestinal disorders.
AB  - The antibacterial activity of plant extracts obtained from Bixa orellana L.,
      Chamomilla recutita L., Ilex paraguariensis A. St.-Hil., Malva sylvestris L.,
      Plantago major L. and Rheum rhaponticum L. has been evaluated against two
      reference strains and eleven clinical isolates of Helicobacter pylori. All the
      plant species chosen are used in popular Brazilian cuisine and folk medicine in
      the treatment of gastrointestinal disorders. Initial screening was made by the
      disk diffusion test and then minimum inhibitory concentration was determined by
      the agar dilution method. The results presented in this work demonstrated that
      among the plant preparations analyzed, B. orellana L., C. recutita L., I.
      paraguariensis A. St.-Hil. and M. sylvestris L. were capable of inhibiting the in
      vitro growth of H. pylori. 

PMID- 24031497
TI  - Antifungal susceptibility profile of Trichosporon isolates: correlation between
      CLSI and etest methodologies.
AB  - The aim of the present study was to evaluate the antifungal susceptibility
      profile of Trichosporon species isolated from different sources employing the
      Clinical and Laboratory Standards Institute (CLSI) method and E-test method.
      Thirty-four isolates of Trichosporon spp. and six CBS reference samples were
      tested for their susceptibility to Amphotericin B, 5-flucytosine, Fluconazole,
      Itraconazole, Voriconazole and Terbinafine. All species showed high Minimun
      Inhibitory Concentrations (MIC) for Itraconazole and susceptibility to
      Fluconazole, The comparison among the results obtained by the CLSI method and E
      test revealed larger discrepancies among 5-flucytosine and Itraconazole. The
      present work provides epidemiological data that could influence therapeutic
      choices. Furthermore, the comparison between different methodologies could help
      to analyze results obtained by different laboratories. 

PMID- 24031498
TI  - Evaluation of different methods for detecting methicillin resistance in
      Staphylococcus aureus isolates in a university hospital located in the Northeast
      of Brazil.
AB  - Many methods have been described for the detection of methicillin-resistant
      Staphylococcus aureus (MRSA), but the heterogeneous expression of methicillin
      resistance affects the reliability of these methods. The aim of the present study
      was to evaluate some methods for detecting methicillin resistance in
      Staphylococcus aureus isolates in a university hospital located in the Northeast
      of Brazil. Among the isolates, 15 were methicillin-susceptible and 45 were
      methicillin-resistant, including low-level heterogeneous resistance strains. Both
      the 30 etag-cefoxitin disk and PBP2a test had 100% sensibility/specificity and
      appear to be good options for the detection of MRSA in the clinical laboratory. 

PMID- 24031499
TI  - Regenerated extracellular NH4 (+) affects the motile chemosensory responses of
      batch-cultured Oxyrrhis marina.
AB  - Regenerated extracellular NH4 (+)in laboratory batch cultures of the
      heterotrophic marine microzooplankter Oxyrrhis marina affects the strength and
      consistency of chemotaxes elicited by synthetic and biogenic chemoattractants.
      The ecological relevance of experiments with batch-cultured O. marina and
      limitations of the microcapillary assay for the study of chemosensory behaviours
      are discussed. 

PMID- 24031500
TI  - Cavitary pneumonia caused by Nocardia otitidiscaviarum.
AB  - We report a case of cavitary pneumonia caused by N. otitidiscaviarum in a man
      with diabetes mellitus and thrombocytopenia treated with systemic corticosteroid.
      Taxonomic identification involved phenotypic testing and molecular identification
      that was carried out by DNA sequencing of the 16SrRNA gene. 

PMID- 24031501
TI  - Epidemiology and antimicrobial resistance of staphylococci isolated from
      different infectious diseases.
AB  - A total of 187 isolates from 470 clinical specimens were collected from three
      hospitals in El-Minia governorate and identified as 132 Staphylococcus aureus
      strains and 55 coagulase-negative staphylococci (CoNS) strains. Susceptibility of
      isolates to antimicrobial agents was tested by the agar dilution method. The
      isolated S. aureus strains showed low resistance to vancomycin (1.5%), amikacin
      (2.3%) and gatifloxacin (3.8%). Vancomycin was the most effective antibiotic
      against CoNS. The ampicillin-resistant isolates were tested for beta-lactamase
      production where, 61.7% of S. aureus and 42.9% of CoNS were positive for beta
      lactamase enzyme. Beta-lactamase producing strains were screened for their
      plasmid profile using alkaline lysis method. Some of these strains carried at
      least one plasmid suggesting plasmid-mediated antibiotic resistance. When cells
      of these strains were exposed to curing agent ethidium bromide, the production of
      the beta-lactamase was lost. Resistance by efflux was studied by a modified
      fluorometric assay. Addition of uncoupler carbonyl cyanide m
      chlorophenylhydrazone (CCCP) increased norfloxacin accumulation in quinolone
      resistant S. aureus strains, suggesting endogenous energy-dependent efflux.
      Combinations of ciprofloxacin with four antimicrobial agents against methicillin
      resistant S.aureus (MRSA) strains were investigated using decimal assay for
      additivity (DAA) technique. Synergistic interaction was observed between
      ciprofloxacin and oxacillin. ciprofloxacin plus cefepime and gentamicin appeared
      to be additive, while ciprofloxacin plus erythromycin was antagonistic. 

PMID- 24031502
TI  - Oral administration of piperine for the control of aflatoxin intoxication in
      rats.
AB  - Aflatoxins are mycotoxins that have important toxic effects on human and animal
      health, even if consumed at low doses. The oral administration of piperine (1.12
      mg/kg) during 23 days in rats seemingly interfered with the toxicity of
      aflatoxins, decreasing hepatic injuries and the leukocyte depletion in
      experimentally intoxicated animals. 

PMID- 24031503
TI  - Prevalence of newcastle disease virus in broiler chickens (Gallus gallus) in
      Brazil.
AB  - This study was carried out during 2002/2003, aiming to determine the prevalence
      of virulent Newcastle disease virus strains (NDV) in Brazilian commercial poultry
      farms. Clinical samples were obtained from the Southeastern, Southern and Central
      Western regions, which comprise the main area of the Brazilian poultry
      production. Serum samples and tracheal and cloacal swabs of 23,745 broiler
      chickens from 1,583 flocks, including both vaccinated chickens and those with no
      vaccination information, were tested for NDV using a diagnostic ELISA kit. The
      seropositivity was 39.1%, and the isolation percentage by flock varied from 1.0
      to 7.6%, and by region from 6.5 to 58.4%. Higher isolation rates (74.3-83.3%)
      were obtained after three passages in embryonated chicken eggs. All isolates
      preliminarily identified as NDV were characterized as nonpathogenic strains, as
      their Intracerebral Pathogenicity Index (ICPI) was below 0.7. Based on results of
      this study, Brazil can claim a virulent NDV-free status for commercial flocks. 

PMID- 24031504
TI  - Seroprevalence of antibodies to Chlamydophila abortus in Ovine in the State of
      Alagoas, Brazil.
AB  - The goal of this study was to perform a seroepidemiological investigation and to
      identify risk factors associated with infection of Chlamydophila abortus of sheep
      herds in the Brazilian state of Alagoas. The study was conducted with samples of
      274 ewes with ages equal to or higher than 24 months in 25 herds and in 23 towns
      located in three regions of the state (Sertao, Agreste and Eastern Alagoas). Anti
      C. abortus antibodies were detected using the microcomplement fixation test. The
      risk factors, were determined based on questionnaires consisting of objective
      questions, about the farmer and general characteristics of the herd like size,
      sanitary situation and reproductive management. Among 274 sera samples analyzed
      for C. abortus, 59 (21.5%) were positive with titers >=32, 187 (68.3%) negative
      and 28 (10.2%) suspect with titers >=16. In the 23 towns studied, 20 had positive
      animals. Among herds 21 (77.7%) of had positive animals. The only variable which
      appeared to be significant in the multivariate analysis was the region, and
      Sertao was the most significant (p<0.001; OR=3.48; T.I. 1.79 - 6.76). Results
      indicate that infection by Chlamydophila abortus is widespread on sheep farms in
      the State of Alagoas. Others studies, however, have to be conducted to isolate
      the agent in order to confirm the role of the bacteria is reproductive
      disturbances in sheeps. In addition to that, control and prophylactic measures
      along with health promoting programs have to be encouraged on the studied farms
      so that infection reates are reduced. 

PMID- 24031505
TI  - Detection of Brucella ovis in ovine from Paraiba State, in the Northeast region
      of Brazil.
AB  - To determine the presence of Brucella ovis in ovine from Paraiba State, in the
      Northeast region of Brazil, 80 animals slaughtered in the public slaughterhouse
      of Patos city were used. Before slaughter, blood samples were collected by
      jugular venopuncture from each animal, and after slaughter, testicles, epidydimus
      and uterus were aseptically collected. For the serological diagnosis of B. ovis
      and B. abortus infections, the agar gel immunodiffusion (AGID) and Rose Bengal
      (RBT) tests were carried out, respectively. In addition, microbiological culture
      and polymerase chain reaction (PCR) were performed on testicle, epidydimus and
      uterus samples. Six animals (7.5%) tested positive for the presence of B. ovis
      antibodies and all animals tested negative for the presence of B. abortus
      antibodies. One AGID-positive animal tested positive at uterine swab culture. PCR
      was able to amplify DNA of Brucella spp. from the pool of testicle, epidydimus
      and uterus samples from AGID-positive animals. This is the first report of
      isolation and detection of B. ovis DNA by PCR in ovine from the Northeast region
      of Brazil. 

PMID- 24031506
TI  - A survey for maintenance of virulent newcastle disease virus-free area in poultry
      production in Brazil.
AB  - In 2003, Brazil was recognized as a pathogenic Newcastle Disease Virus (NDV)
      strain-free country for commercial poultry. This research was conducted in Brazil
      between December 2003 and March 2005 to verify the maintenance of this virulent
      NDV-free status. Serum samples from 5,455 flocks for commercial poultry farms
      were collected, comprising 81,825 broiler chickens. The farms were located in
      nine states of the country, grouped in three geographic regions. Serological
      evidence of NDV infection was detected in 28.8% of the surveyed farms. However,
      all fifteen viruses isolated and identified as Newcastle Disease Virus (NDV) were
      characterized as nonpathogenic strains, based on the Intracerebral Pathogenicity
      Index. These results showed that Brazil preserves the virulent NDV-free status
      for commercial flocks. 

PMID- 24031507
TI  - Occurrence of Staphylococcus aureus in raw milk produced in dairy farms in Sao
      Paulo state, Brazil.
AB  - The objective of the present study was to evaluate the occurrence of
      Staphylococcus aureus in milk produced in 37 farms located in the regions of
      Ribeirao Preto and Sao Carlos, state of Sao Paulo, Brazil. Two-hundred and eight
      samples of milk from individual cows showing subclinical mastitis, and 37 samples
      of bulk tank milk were analyzed. S. aureus strains were detected in 18 (7.3%)
      milk samples: 14 (6.7%) from samples of individual cows, and 4 (10.8%) from bulk
      tank milk. Two individual milk samples (14.3%) and two bulk milk samples
      contained enterotoxigenic S. aureus. PFGE analysis revealed the genetic
      heterogeneity of the strains isolated from raw milk, which presented to 13 S.
      aureus patterns. Results confirmed the potential transmission of staphylococcal
      food poisoning to consumers via milk of cows affected by subclinical mastitis,
      mainly when raw milk is ingested. 

PMID- 24031508
TI  - Molecular detection of Anaplasma platys in a naturally-infected cat in Brazil.
AB  - Following the accidental finding of inclusion bodies similar to Anaplasma platys
      in a stained blood smear from a cat, DNA analysis of the 16S rRNA gene was
      performed and 100% identity was found with different strains of A. platys. These
      data confirm that cats are susceptible to parasitism by A. platys. 

PMID- 24031509
TI  - Detection of Mycobacterium bovis DNA in nasal swabs from tuberculous cattle by a
      multiplex PCR.
AB  - Detection of tuberculosis in cattle relies on the intradermal tuberculin test
      (ITT), but a definitive diagnosis requires identification of the pathogen after
      the animal is slaughtered. DNA in nasal swabs from 50 cows was analyzed by m-PCR,
      targeting for the RvD1-Rv2031c and IS6110 sequences. M. bovis was identified in
      two of 34 tuberculous cows (5.9%). The use of mPCR of nasal swabs as an in vivo
      diagnostic tool for bovine tuberculosis is suggested. 

PMID- 24031510
TI  - Structure and composition of bacterial and fungal community in soil under soybean
      monoculture in the Brazilian Cerrado.
AB  - Soybean is the most important oilseed cultivated in the world and Brazil is the
      second major producer. Expansion of soybean cultivation has direct and indirect
      impacts on natural habitats of high conservation value, such as the Brazilian
      savannas (Cerrado). In addition to deforestation, land conversion includes the
      use of fertilizers and pesticides and can lead to changes in the soil microbial
      communities. This study evaluated the soil bacterial and fungal communities and
      the microbial biomass C in a native Cerrado and in a similar no-tillage soybean
      monoculture area using PCR-DGGE and sequencing of bands. Compared to the native
      area, microbial biomass C was lower in the soybean area and cluster analysis
      indicated that the structure of soil microbial communities differed. 16S and 18S
      rDNA dendrograms analysis did not show differences between row and inter-row
      samples, but microbial biomass C values were higher in inter-rows during soybean
      fructification and harvest. The study pointed to different responses and
      alterations in bacterial and fungal communities due to soil cover changes (fallow
      x growth period) and crop development. These changes might be related to
      differences in the pattern of root exudates affecting the soil microbial
      community. Among the bands chosen for sequencing there was a predominance of
      actinobacteria, gamma-proteobacteria and ascomycetous divisions. Even under no
      tillage management methods, the soil microbial community was affected due to
      changes in the soil cover and crop development, hence warning of the impacts
      caused by changes in land use. 

PMID- 24031511
TI  - Integrated control of Penicillium digitatum by the predacious yeast
      Saccharomycopsis crataegensis and sodium bicarbonate on oranges.
AB  - Our investigation of integrated biological control (IBC) started with an assay
      testing activity of the predacious yeast Saccharomycopsis crataegensis UFMG
      DC19.2 against Penicillium digitatum LCP 4354, a very aggressive fungus that
      causes postharvest decay in oranges. Under unfavourable environmental conditions,
      the yeast showed a high potential for control (39.9% disease severity reduction)
      of this fungus. This result was decisive for the next step, in which S.
      crataegensis was tested in association with sodium bicarbonate salt, a generally
      regarded as safe (GRAS) substance. The yeast was able to survive at different
      concentrations of the salt (1%, 2% and 5%), and continued to grow for a week at
      the wound site, remaining viable at high population for 14 days on the fruit
      surface. The yeast alone reduced the severity of decay by 41.7% and sodium
      bicarbonate alone reduced severity of decay by 19.8%, whereas the application of
      both led to a delay in the development of symptoms from 2 to 10 days. Ingredients
      of the formulations were not aggressive to fruits since no lesions were produced
      in control experiments. 

PMID- 24031512
TI  - Bacterial community analysis of the water surface layer from a rice-planted and
      an unplanted flooded field.
AB  - The bacterial communities in floodwater, from a rice-planted and an unplanted
      field were characterized at the beginning (flooding stage) and at the end
      (harvest stage) of the rice cropping cycle. Most probable number estimations and
      plate counts of aerobic and anaerobic heterotrophic bacteria and of several
      metabolic bacterial groups (methanogens, sulfate-reducers, anaerobic sulfur and
      nonsulfur phototrophs, denitrifiers and ammonifiers) were similar in rice and
      unplanted floodwater at both sampling times. The analysis of denitrifiers and
      methanogens by fluorescent in situ hybridization revealed a shift in the
      phylogenetic affiliation only of the former group in the rice-planted floodwater.
      Terminal restriction fragment length polymorphism of 16S rRNA gene amplicons
      indicated that the bacterial communities of the rice-planted and unplanted soils
      were consistently diverse and strongly influenced by the season. 

PMID- 24031513
TI  - Leishmanicidal, trypanocidal, and cytotoxic activities of endophytic fungi
      associated with bioactive plants in Brazil.
AB  - One hundred and twenty-one isolates of endophytic fungi were recovered from
      leaves of the bioactive Brazilian plant species Ageratum myriadenia , Palicourea
      tetraphylla , Piptadenia adiantoides, and Trixis vauthieri. All fungal isolates
      were cultivated in liquid media and crude extracts were obtained with ethyl
      acetate. The crude extracts were tested in bioassay panels using Leishmania
      amazonensis , Trypanosoma cruzi, the enzyme trypanothione reductase (TryR) from
      Trypanosoma cruzi, and three human cancer cell lines. Thirty-three extracts
      (27.2%) exhibited at least one biological activity. Seventeen extracts (14%) were
      cytotoxic against one or more human cancer cell line with the IC50 values ranged
      of >0.2 to 25 ug/mL. Twenty-four extracts (19.8%) inhibited the activity of TryR,
      and three showed ability to inhibit the growth of T. cruzi above 60% and their
      IC50 values ranged among 1 to 10 ug/mL. Eleven extracts (9%) were able to inhibit
      the growth of L. amazonensis and showed with IC50 values ranged among 4.6 to 24.4
      ug/mL. The endophytic fungi were identified as belonging to the genera Alternaria
      , Arthrinium , Cochliobolus , Colletotrichum , Penicillium , Fusarium, and
      Gibberella. An interesting result was obtained for the bioactive isolates UFMGCB
      508, 537, 899 and 903, which were related to fungi associated with medicinal
      plants native to Asia, Australia, Africa, and Polynesia. These results indicate
      that bioactive plants living in Brazilian ecosystems are a potential host of
      endophytic fungi able to produce bioactive prototype molecules for drug
      development against neglected tropical diseases. 

PMID- 24031514
TI  - Co-metabolism of DDT by the newly isolated bacterium, Pseudoxanthomonas sp. wax.
AB  - Microbial degradation of 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) is
      the most promising way to clean up DDT residues found in the environment. In this
      paper, a bacterium designated as wax, which was capable of co-metabolizing DDT
      with other carbon sources, was isolated from a long-term DDT-contaminated soil
      sample by an enrichment culture technique. The new isolate was identified as a
      member of the Pseudoxanthomonas sp., based on its morphological, physiological
      and biochemical properties, as well as by 16S rRNA gene analysis. In the presence
      of 100 mg l(-1) glucose, the wax strain could degrade over 95% of the total DDT,
      at a concentration of 20 mg l(-1), in 72 hours, and could degrade over 60% of the
      total DDT, at a concentration of 100 mg l(-1), in 144 hours. The wax strain had
      the highest degradation efficiency among all of the documented DDT-degrading
      bacteria. The wax strain could efficiently degrade DDT at temperatures ranging
      from 20 to 37 degrees C, and with initial pH values ranging from 7 to 9. The
      bacterium could also simultaneously co-metabolize 1,1-dichloro-2,2-bis(p
      chlorophenyl)ethane (DDD), 2,2-bis(p-chlorophenyl)-1,1-dichlorethylene (DDE), and
      other organochlorine compounds. The wax strain could also completely remove 20 mg
      kg(-1) of DDT from both sterile and non-sterile soils in 20 days. This study
      demonstrates the significant potential use of Pseudoxanthomonas sp. wax for the
      bioremediation of DDT in the environment. 

PMID- 24031515
TI  - Biological control of potato black scurf by rhizosphere associated bacteria.
AB  - The present work was carried out to study the potential of plant rhizosphere
      associated bacteria for the biocontrol of potato black scurf disease caused by
      Rhizoctonia solani Khun AG-3. A total of twenty-eight bacteria isolated from
      diseased and healthy potato plants grown in the soil of Naran and Faisalabad,
      Pakistan were evaluated for their antagonistic potential. Nine bacterial strains
      were found to be antagonistic in vitro, reduced the fungal growth and caused the
      lysis of sclerotia of R. solani in dual culture assay as well as in extracellular
      metabolite efficacy test. The selected antagonistic strains were further tested
      for the production and efficacy of volatile and diffusible antibiotics, lytic
      enzymes and siderophores against R. solani. Selected antagonistic bacteria were
      also characterized for growth promoting attributes i.e., phosphate
      solubilization, nitrogen fixation and indole acetic acid production. Biocontrol
      efficacy and percent yield increase by these antagonists was estimated in
      greenhouse experiment. Statistical analysis showed that two Pseudomonas spp. StT2
      and StS3 were the most effective with 65.1 and 73.9 percent biocontrol efficacy,
      as well as 87.3 and 98.3 percent yield increase, respectively. Potential
      antagonistic bacterial strain StS3 showed maximum homology to Pseudomonas sp. as
      determined by 16S rRNA gene sequencing. These results suggest that bacterial
      isolates StS3 and StT2 have excellent potential to be used as effective
      biocontrol agents promoting plant growth with reduced disease incidence. 

PMID- 24031516
TI  - Characterization of Aeromonas species isolated from an estuarine environment.
AB  - Thirty water samples were collected, at two week intervals, from the estuary of
      the River Coco. The aim was to characterize the presence, distribution and types
      of Aeromonas spp, in the estuary of the River Coco, Ceara, Brazil (03 degrees
      46'28.83''S e 38 degrees 26'36.52''S). Aeromonas were identified in 19 (63%)
      samples analyzed by plating and CFU counts. Presence/absence tests were positive
      for 11 (37%) of the samples resulting in the detection of Aeromonas in a total of
      23 (77%) of samples. CFU counts varied from < 10 to 1.4 x 10(4) CFU mL(-1). From
      the isolated strains seven species of Aeromonas were identified: A. caviae
      (29/69), A. veronii bv. sobria (13/69), A. veronii bv. veronii (8/69), A. trota
      (6/69), A. media (5/69), A. sobria (4/69) and A. hydrophila and Aeromonas sp.
      (2/69). Of the 38 strains tested, 23 (60%) showed resistance to at least one of
      the eight antimicrobials. Multiple resistance to antibiotics was observed in A.
      caviae, A. media , A. sobria and A. veronii bv. sobria. Aeromonas caviae showed
      the highest multiple resistance, being resistant to four antibiotics. The
      presence of those microorganisms may contribute to the occurrence of
      gastroenteritis, mainly in children, since they are considered opportunists. 

PMID- 24031517
TI  - Biosynthesis of selenium nanoparticles using Klebsiella pneumoniae and their
      recovery by a simple sterilization process.
AB  - The use of biologically derived metal nanoparticles for various proposes is going
      to be an issue of considerable importance; thus, appropriate methods should be
      developed and tested for the biological synthesis and recovery of these
      nanoparticles from bacterial cells. In this research study, a strain of
      Klebsiella pneumoniae was tested for its ability to synthesize elemental selenium
      nanoparticles from selenium chloride. A broth of Klebsiella pneumoniae culture
      containing selenium nanoparticles was subjected to sterilization at 121(o)C and
      17 psi for 20 minutes. Released selenium nanoparticles ranged in size from 100 to
      550 nm, with an average size of 245 nm. Our study also showed that no chemical
      changes occurred in selenium nanoparticles during the wet heat sterilization
      process. Therefore, the wet heat sterilization process can be used successfully
      to recover elemental selenium from bacterial cells. 

PMID- 24031518
TI  - One-step purification and characterization of cellulase-free xylanase produced by
      alkalophilic Bacillus subtilis ash.
AB  - The present study describes the one-step purification and characterization of an
      extracellular cellulase-free xylanase from a newly isolated alkalophilic and
      moderately thermophilic strain of Bacillus subtilis ASH. Xylanase was purified to
      homogeneity by 10.5-fold with ~43% recovery using ion-exchange chromatography
      through CM-Sephadex C-50. The purified enzyme revealed a single band on SDS-PAGE
      gel with a molecular mass of 23 kDa. It showed an optimum pH at 7.0 and was
      stable over the pH range 6.0-9.0. The optimum temperature for enzyme activity was
      55  degrees C. The purified xylanase did not lose any activity up to 45 oC,
      however, it retained 80% and 51% of its activity after pre-incubation at 55 oC
      and 60 oC, respectively. The enzyme obeyed Michaelis-Menton kinetics towards
      birch wood xylan with apparent Km 3.33 mg/ml and Vmax 100 IU/ml. The enzyme was
      strongly inhibited by Hg(2+)and Cu(2+)while enhanced by Co(2+) and Mn(2+). The
      purified enzyme could be stored at 4 oC for six weeks without any loss of
      catalytic activity. The faster and economical purification of the cellulase-free
      xylanase from B. subtilis ASH by one-step procedure together with its appreciable
      stability at high temperature and alkaline pH makes it potentially effective for
      industrial applications. 

PMID- 24031519
TI  - Construction of killer industrial yeast Saccharomyces cerevisiae hau-1 and its
      fermentation performance.
AB  - Saccharomyces cerevisiae HAU-1, a time tested industrial yeast possesses most of
      the desirable fermentation characteristics like fast growth and fermentation
      rate, osmotolerance, high ethanol tolerance, ability to ferment molasses, and to
      ferment at elevated temperatures etc. However, this yeast was found to be
      sensitive against the killer strains of Saccharomyces cerevisiae. In the present
      study, killer trait was introduced into Saccharomyces cerevisiae HAU-1 by
      protoplast fusion with Saccharomyces cerevisiae MTCC 475, a killer strain. The
      resultant fusants were characterized for desirable fermentation characteristics.
      All the technologically important characteristics of distillery yeast
      Saccharomyces cerevisiae HAU-1 were retained in the fusants, and in addition the
      killer trait was also introduced into them. Further, the killer activity was
      found to be stably maintained during hostile conditions of ethanol fermentations
      in dextrose or molasses, and even during biomass recycling. 

PMID- 24031520
TI  - Identification of lactic acid bacteria associated with traditional cachaca
      fermentations.
AB  - During the production of traditional cachaca (alembic's cachaca), contamination
      of the fermented must is one of the factors leading to economic losses in the
      beverage manufacturing industry. The diversity of bacterial populations and the
      role of these microorganisms during the cachaca production process are still
      poorly understood in Brazil. In our work, the fermentation process was followed
      in two distilleries located in the state of Minas Gerais. The objective of this
      work was to identify the populations of lactic acid bacteria present during
      cachaca fermentation using physiological and molecular methods. Lactic acid
      bacteria were isolated in high frequencies during all of the fermentative
      processes, and Lactobacillus plantarum and L. casei were the most prevalent
      species. Other lactic acid bacteria were found in minor frequencies, such as L.
      ferintoshensis, L. fermentum, L. jensenii, L. murinus, Lactococcus lactis,
      Enterococcus sp. and Weissella confusa. These bacteria could contribute to the
      increase of volatile acidity levels or to the production of compounds that could
      influence the taste and aroma of the beverage. 

PMID- 24031521
TI  - Improved adsorption-desorption extraction applied to the partial characterization
      of the antilisterial bacteriocin produced by Carnobacterium maltaromaticum C2.
AB  - Bacteriocins are ribosomally produced peptides useful for food biopreservation.
      An improved adsorption-desorption process is proposed for the partial
      purification of the bacteriocin produced by the fish isolate Carnobacterium
      maltaromaticum C2. Analyzis of extract by SDS-PAGE indicated this method may
      offer an alternative to improve the yield of purification of bacteriocins. 

PMID- 24031522
TI  - Ciprofloxacin susceptibility reduction of Salmonella strains isolated from
      outbreaks.
AB  - The antimicrobial susceptibility of 212 Salmonella strains isolated from patients
      and foods was evaluated and 45% were found to be resistant to nalidixic acid.
      Nalidixic acid resistant strains showed a higher minimal inhibitory concentration
      for ciprofloxacin than sensitive strains. During the study an increase of strains
      with reduced susceptibility to ciprofloxacin was also observed. 

PMID- 24031523
TI  - Effect of refrigeration and frozen storage on the Campylobacter jejuni recovery
      from naturally contaminated broiler carcasses.
AB  - Campylobacter jejuni is the most common thermophilic Campylobacter associated
      with human enteritis in many countries. Broilers and their by-products are the
      main sources for human enteritis. Refrigeration and freezing are used to control
      bacterial growth in foods. The effect of these interventions on survival of
      Campylobacter jejuni is yet not quite understood. This study evaluated the effect
      of storage temperature on the survival of C. jejuni in chicken meat stored for
      seven days at 4 degrees C and for 28 days at -20 degrees C. The influence of
      selective enrichment on recovery of Campylobacter was also evaluated. Thirty
      fresh chicken meat samples were analyzed and 93.3% was contaminated with
      termotolerant Campylobacter spp. with average count of 3.08 Log10 CFU/g on direct
      plating. After refrigeration, 53.3% of the analyzed samples tested positive for
      Campylobacter and the average count was 1.19 Log10 CFU/g. After storage at -20
      degrees C, 36.6% of the samples were positive with a verage count of 0.75 Log10
      CFU/g. C. jejuni was detected after enrichment, respectively, in 50% of the
      fresh, 36.7% of the refrigerated and 33.3% of the frozen meat samples analyzed.
      No difference was detected for the recovery of C. jejuni from fresh, refrigerated
      or frozen samples after selective enrichment, showing that this microorganism can
      survive under the tested storage conditions. 

PMID- 24031524
TI  - Comparison of radial growth rate of the mutualistic fungus of Atta sexdens
      rubropilosa forel in two culture media.
AB  - In vitro culture of the mutualistic fungus of leaf-cutting ants is troublesome
      due to its low growth rate, which leads to storage problems and contaminants
      accumulation. This paper aims at comparing the radial growth rate of the
      mutualistic fungus of Atta sexdens rubropilosa Forel in two different culture
      media (Pagnocca B and MEA LP). Although total MEA LP radial growth was greater
      all along the bioassay, no significant difference was detected between growth
      efficiencies of the two media. Previous evidences of low growth rate for this
      fungus were confirmed. Since these data cannot point greater efficiency of one
      culture medium over the other, MEA LP medium is indicated for in vitro studies
      with this mutualistic fungus due its simpler composition and translucent color,
      making the analysis easier. 

PMID- 24031525
TI  - Identification of GRP75 as a novel PreS1 binding protein using a proteomics
      strategy.
AB  - The PreS1 region of the L protein is important in cell attachment and
      consequently in hepatitis B virus (HBV) infectivity. To identify novel PreS1
      interacting protein, we performed Glutathione-S-transferase (GST) pull-down, two
      dimensional gel electrophoresis (2-DE) and mass spectrometry assays. Glucose
      regulated proteins (GRP) 78 and 75 were found to bind PreS1. The interactions
      between PreS1 and GRP75 were confirmed by a co-immunoprecipitation experiment.
      GRP78 and GRP75 may play important roles in mediating HBV virion entering into
      hepatocyte and regulating proper folding of the L protein due to their critical
      functions in protein folding and trafficking. The finding of novel PreS1 binding
      protein enriches our knowledge about molecular mechanism of HBV infection. 

PMID- 24031526
TI  - Microbial production of biovanillin.
AB  - This review aims at providing an overview on the microbial production of
      vanillin, a new alternative method for the production of this important flavor of
      the food industry, which has the potential to become economically competitive in
      the next future. After a brief description of the applications of vanillin in
      different industrial sectors and of its physicochemical properties, we described
      the traditional ways of providing vanillin, specifically extraction and chemical
      synthesis (mainly oxidation) and compared them with the new biotechnological
      options, i.e., biotransformations of caffeic acid, veratraldehyde and mainly
      ferulic acid. In the second part of the review, emphasis has been addressed to
      the factors most influencing the bioproduction of vanillin, specifically the age
      of inoculum, pH, temperature, type of co-substrate, as well as the inhibitory
      effects exerted either by excess substrate or product. The final part of the work
      summarized the downstream processes and the related unit operations involved in
      the recovery of vanillin from the bioconversion medium. 

PMID- 24031527
TI  - Potential application of new diagnostic methods for controlling bovine
      tuberculosis in Brazil.
AB  - Bovine tuberculosis, a chronic infection in cattle caused by Mycobacterium bovis,
      remains an economic and public health problem for several countries. Due to its
      economic impact on international trade, contagious nature, and implications for
      human health, global programs to eradicate the disease were implemented
      worldwide. Those programs are based on slaughtering PPD-reactive animals. Despite
      the National Programs in Brazil, complete eradication has not been achieved, and
      the disease remains, albeit at a lower prevalence. The central purpose of this
      review is to address diagnostic tests for tuberculosis. Considering the course of
      the infection in cattle, at least two tests, ideally complementary to one
      another, may be necessary for an adequate diagnosis: the first based on the
      cellular response, and the second capable of identifying anergic animals by
      detection of specific anti-M.bovis antibodies. 

PMID- 24031528
TI  - Bacteriocins - exploring alternatives to antibiotics in mastitis treatment.
AB  - Mastitis is considered to be the most costly disease affecting the dairy
      industry. Management strategies involve the extensive use of antibiotics to treat
      and prevent this disease. Prophylactic dosages of antibiotics used in mastitis
      control programmes could select for strains with resistance to antibiotics. In
      addition, a strong drive towards reducing antibiotic residues in animal food
      products has lead to research in finding alternative antimicrobial agents. In
      this review we have focus on the pathogenesis of the mastitis in dairy cows,
      existing antibiotic treatments and possible alternative for application of
      bacteriocins from lactic acid bacteria in the treatment and prevention of this
      disease. 

PMID- 24031529
TI  - Detection of human cytomegalovirus and epstein-barr virus in coronary
      atherosclerotic tissue.
AB  - Previous studies indicated that patients with atherosclerosis are predominantly
      infected by human cytomegalovirus (HCMV), but rarely infected by type 1 Epstein
      Barr virus (EBV-1). In this study, atheromas of 30 patients who underwent
      aortocoronary bypass surgery with coronary endartherectomy were tested for the
      presence of these two viruses. HCMV occurred in 93.3% of the samples and EBV-1
      was present in 50% of them. Concurrent presence of both pathogens was detected in
      43.3% of the samples. 

PMID- 24031530
TI  - Antibacterial susceptibility patterns and cross-resistance of methicillin
      resistant and sensitive staphyloccus aureus isolated from the hospitalized
      patients in shiraz, iran.
AB  - Nosocomial infections caused by methicillin-resistant staphylococci (MRSA) pose a
      serious problem in many countries. This study aimed to determine the
      antibacterial susceptibility patterns of methicillin sensitive and resistant
      Staphylococcus aureus isolates from the hospitalized patients. Totally 356
      isolates of Staphylococcus aureus (S. aureus) including 200, 137 and 19
      corresponding to MSSA, MRSA, and intermediate MRSA strains, respectively were
      isolated. Antibacterial susceptibility patterns of the isolates to 14 antibiotics
      were examined using Kirby-Bauer method. MICs of 15 antibiotics to 156 MRSA
      isolates were determined by E test method. Cross-resistances of MRSA isolates
      (137+19) to the other tested antibiotics were also determined. S.aureus with high
      frequencies were isolated from the blood, sputum and deep wound samples. All of
      200 MSSA isolates were sensitive to oxacillin, vancomycin, tecoplanin, rifampin,
      linezolid, quinupristin/dalfopristin, mupirocin and fusidic acid. A gradient of
      reduced susceptibility of MSSA to cephalexin, co-trimoxazole, ciprofloxacin,
      clindamycin, tetracycline, erythromycin and gentamicin were evident. MRSA
      isolates were sensitive to vancomycin, tecoplanin, linezolid,
      quinupristin/dalfopristin, mupirocin and fusidic acid, while reduced
      susceptibility of them to rifampin, co-trimoxazole, clindamycin, cephalexin,
      tetracycline, ciprofloxacin, erythromycin and gentamicin were observed. MRSA
      isolates exhibited a high range of cross-resistance to the eight tested
      antibiotics. Overall, co-trimoxazole, ciprofloxacin, clindamycin, tetracycline,
      erythromycin and gentamicin showed low activity against MSSA and MRSA isolates
      which may indicate they are not suitable to be used in clinical practices. To
      preserve the effectiveness of antibiotics, rational prescription and concomitant
      application of preventive measures against the spread of MRSA are recommended. 

PMID- 24031531
TI  - Effect of galbanic Acid, a sesquiterpene coumarin from ferula szowitsiana, as an
      inhibitor of efflux mechanism in resistant clinical isolates of Staphylococcus
      aureus.
AB  - Galbanic acid, a sesquiterpene coumarin from Ferula szowitsiana roots, was
      investigated for its potentiating effect on the antimicrobial activity of
      antibiotics as well as ethidium bromide, in 6 multidrug resistance (MDR) clinical
      isolates of Staphylococcus aureus. Galbanic acid had inhibitory effect on none of
      the isolated bacteria tested (up to 800 MUg /ml). The MIC range of ciprofloxacin,
      tetracycline and ethidium bromide, against all tested S. aureus were 10-80, 10-80
      and 4-16 MUg/ml, respectively. These were reduced to <=2.5-5, 2.5-5 and 0.5-2
      MUg/ml in the presence of galbanic acid (300 MUg /ml) or verapamil (100 MUg /ml).
      The rate of ethidium bromide (2 MUg /ml) accumulation in clinical isolates was
      enhanced with galbanic acid (300 MUg /ml). There is also a decrease in loss of
      ethidium bromide from bacteria in the presence of galbanic acid. Similar results
      were obtained when verapamil (100 MUg /ml) was used as an efflux pump inhibitor.
      Galbanic acid, like verapamil, a typical inhibitor of efflux pump, reduced the
      MIC of ethidium bromide and tested antibiotics. Since efflux is the only known
      reported mechanism for ethidium bromide resistance, the reduction in ethidium
      bromide MIC and enhanced accumulation as well as decreased efflux of ethidium
      bromide in the presence of galbanic acid, can be attributed to this efflux
      inhibitory properties. 

PMID- 24031532
TI  - Antibacterial activity of extracts of acacia aroma against methicillin-resistant
      and methicillin-sensitive Staphylococcus.
AB  - Antibacterial activity of organic and aqueous extracts of Acacia aroma was
      evaluated against methicillin-resistant Staphylococcus aureus (MRSA), methicillin
      sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus
      epidermidis. Inhibition of bacterial growth was determined using agar diffusion
      and bioautographic methods. Among all assayed organic extracts only ethanolic and
      ethyl acetate extracts presented highest activities against all tested
      Staphylococcus strains with minimal inhibitory concentration (MIC) values ranging
      from 2.5 to 10 mg/ml and from 2.5 to 5 mg/ml respectively. The aqueous extracts
      show little antibacterial activity against Staphylococcus strains. The
      bioautography assay demonstrated well-defined growth inhibition zones against S.
      aureus in correspondence with flavonoids and saponins. A. aroma would be an
      interesting topic for further study and possibly for an alternative treatment for
      skin infections. 

PMID- 24031533
TI  - Prevalence of virulence genes among bulgarian nosocomial and cystic fibrosis
      isolates of pseudomonas aeruginosa.
AB  - The aim of this study was to evaluate the prevalence of some virulence genes
      among 202 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients
      (n=42) and non-CF in-patients (n=160) and to analyze the values according to the
      patient groups, infection localization and antimicrobial resistance. The
      following frequencies in all studied strains were established: algD (encoding GDP
      mannose 6-dehydrogenase AlgD) - 91.1%, pilB (type IV fimbrial biogenesis protein
      PilB) - 23.8%, nan1 (neuraminidase) - 21.3%, lasB (elastase LasB) - 100%, plcH
      (haemolytic phospholipase C precursor) - 91.6%, exoS (exoenzyme S) - 62.4%, and
      exoU (exoenzyme U) - 30.2%. The prevalence of nan1 was significantly higher
      (P<0.01) in CF isolates (38.1%) than that in non-CF isolates (16.9%). The nan1
      positive CF strains were cultured from 16 patients with recurrent lung
      exacerbations. This study revealed a statistically significant difference
      (P<0.01) between the portion of multidrug-resistant (MDR) nosocomial P.
      aeruginosa strains containing a large number (>=5) of virulence genes (38.1%) and
      the respective part of non-MDR isolates (17.6%). Moreover, pilB, exoU and nan1
      manifested a higher spread (P<0.001) among MDR than in non-MDR strains
      (respectively, 39.1% vs. 13.2%; 40.2% vs. 17.7% and 26.1% vs. 4.4%). In
      conclusion, the dissemination of nan1 in CF isolates was moderate and correlated
      with the lower proportion of patients with lung exacerbations. The molecular
      genetic detection of this gene may be used as an indirect measure of CF pulmonary
      disease evolution. Simultaneous determination of virulence factors and
      antimicrobial resistance is the contemporary approach for examination of the
      microbiological aspects of infections caused by P. aeruginosa. 

PMID- 24031534
TI  - Ampc Beta lactamases among gram negative clinical isolates from a tertiary
      hospital, South India.
AB  - AmpC beta-lactamases are cephalosporinases that hydrolyze cephamycins as well as
      other extended-spectrum cephalosporins and are poorly inhibited by clavulanic
      acid. Although reported with increasing frequency, the true rate of occurrence of
      AmpC beta-lactamases in different organisms, including members of
      Enterobacteriaceae, remains unknown. The present study was designed to determine
      the occurrence of AmpC enzyme-harbouring Gram-negative clinical isolates in a
      tertiary care hospital in Pondicherry state, South India. A total of 235 Gram
      negative clinical isolates were tested for resistance to cefoxitin, third
      generation cephalosporin (3GC) antibiotics, ampicillin, amikacin, co-trimoxazole,
      gentamicin, meropenem and tetracycline by disc diffusion method. Isolates found
      resistant to 3GC and cefoxitin were tested for the production of AmpC beta 
      lactamases by three dimensional extraction method and AmpC disc method. Isolates
      found to sensitive to 3GC were subjected to disc antagonism test for inducible
      AmpC production. One hundred and thirty four (57%) strains were resistant to 3GC,
      among which 63(47%) were positive for plasmid-mediated AmpC beta lactamases
      production. Among the 101 strains sensitive to 3GC, 23 (22.7%) revealed the
      presence of inducible AmpC beta lactamases by disc approximation test. A total of
      80.9% (51/63) of screen positive isolates were detected by Amp C disc test and
      93.6% (59/63) by three dimensional extraction method. Out of the 86 AmpC
      producers, 67 (77.9%) were cefoxitin resistant .Inducible AmpC was not found in
      Esch.coli and Klebsiella spp. The AmpC producers also concurrently showed
      multidrug resistance pattern. AmpC producers were found to be prevalent in our
      hospital and though three dimensional extraction test detects AmpC better, the
      disk test is easier to perform routinely and is user- friendly. 

PMID- 24031535
TI  - Distribution, detection of enterotoxigenic strains and antimicrobial drug
      susceptibility patterns of bacteroides fragilis group in diarrheic and non
      diarrheic feces from brazilian infants.
AB  - Despite the importance of gastrointestinal diseases and their global
      distribution, affecting millions of individuals around the world, the role and
      antimicrobial susceptibility patterns of anaerobic bacteria such as those in the
      Bacteroides fragilis group (BFG) are still unclear in young children. This study
      investigated the occurrence and distribution of species in the BFG and
      enterotoxigenic strains in the fecal microbiota of children and their
      antimicrobial susceptibility patterns. Diarrheic (n=110) and non-diarrheic (n=65)
      fecal samples from children aged 0-5 years old were evaluated. BFG strains were
      isolated and identified by conventional biochemical, physiological and molecular
      approaches. Alternatively, bacteria and enterotoxigenic strains were detected
      directly from feces by molecular biology. Antimicrobial drug susceptibility
      patterns were determined by the agar dilution method according to the guidelines
      for isolated bacteria. BFG was detected in 64.3% of the fecal samples (55%
      diarrheic and 80.4% non-diarrheic), and 4.6% were enterotoxigenic. Antimicrobial
      resistance was observed against ampicillin, ampicillin/sulbactam,
      piperacillin/tazobactam, meropenem, ceftriaxone, clindamycin and chloramphenicol.
      The data show that these bacteria are prevalent in fecal microbiota at higher
      levels in healthy children. The molecular methodology was more effective in
      identifying the B. fragilis group when compared to the biochemical and
      physiological techniques. The observation of high resistance levels stimulates
      thoughts about the indiscriminate use of antimicrobial drugs in early infancy.
      Further quantitative studies are needed to gain a better understanding of the
      role of these bacteria in acute diarrhea in children. 

PMID- 24031536
TI  - Rauvolfia grandiflora (apocynaceae) extract interferes with staphylococcal
      density, enterotoxin production and antimicrobial activity.
AB  - Staphylococci bacteria are involved in many human and animal infections and
      development of alternative antimicrobial drugs against pathogenic bacteria is of
      great interest to the pharmaceutical industry. This study investigated the in
      vitro effect of Rauvolfia grandiflora methanol extract (root bark fraction) (RGE)
      on the density of ATCC strains of Staphylococcus aureus and Staphylococcus
      epidermidis, and a clinical enterotoxin-producer, S. aureus bovine strain. The
      alkaloid, isoreserpiline, obtained from dichloromethane extract of R. grandiflora
      was ineffective against the strains tested. After incubation of staphylococci
      strains in the presence of 1.2 MUg.mL(-1) RGE, a significant inhibition of cell
      growth was observed using both spectrophotometry and ELISA assays. Twelve drugs
      were evaluated for their antimicrobial effects on culture RGE-treated cells using
      the disk diffusion method. Penicillin resistant strains became sensitive to the
      drug after RGE treatment. Furthermore, enterotoxin production by RGE-treated S.
      aureus was evaluated using a standardized ELISA method. Although staphylococcal
      LSA 88 bovine strain cells remained viable after exposure to the extract,
      enterotoxin production was precluded in 20% after RGE treatment. Significant
      interference in staphylococci cell density, drug sensitivity and enterotoxin
      secretion was observed after treatment. The study highlights the necessity to
      find new methods of disease prevention and new antibiotic therapies against
      staphylococcal infections. 

PMID- 24031537
TI  - Effects of myrcia ovata cambess. Essential oil on planktonic growth of
      gastrointestinal microorganisms and biofilm formation of enterococcus faecalis.
AB  - The essential oil from the leaves of Myrcia ovata Cambess., commonly used in
      Brazil for the treatment of gastric illnesses, was screened for antimicrobial
      activity and action in the formation of microbial biofilms by Enterococcus
      faecalis. The oil was obtained by hydrodistillation using a clevenger-type
      system. Its chemical composition was analyzed using GC and GC-MS. Both MIC and
      MBC of the essential oil were determined by broth microdilution techniques and
      agar dilution method. The essential oil showed antimicrobial activity against E.
      faecalis, Escherichia coli, Pseudomonas aeruginosa, Salmonella choleraesuis,
      Staphylococcus aureus, Streptococcus pneumoniae and Candida parapsilosis. The
      results showed that the essential oil of M. ovata Cambess. was effective against
      the formation of biofilm by E. faecalis when compared with the control. Four
      volatile compounds, representing 92.1 % of the oil, were identified and geranial
      was the major component (50.4 %). At the best of our knowledge, this is the first
      report of the chemical composition and antimicrobial activity of the essential
      oil from leaves of M. ovata. 

PMID- 24031538
TI  - Trichosporon species isolated from the perigenital region, urine and catheters of
      a brazilian population.
AB  - The present study aimed to 1) determine the colonization rates of medically
      important Trichosporon species on normal perigenital skin and 2) determine the
      isolation rates of Trichosporon spp. isolated from the urine and catheters of
      Brazilian patients hospitalized in the Intensive Care Unit (ICU). The overall
      colonization rate of Trichosporon spp. was 11.15% (112 isolates). The most common
      species isolated from normal perigenital skin was T. cutaneum (29.46%), followed
      by T. asteroides (20.53%), T. ovoides (15.17%), T. inkin (10.71%), T. mucoides
      (8.92%), and T. asahii (6.25%). From urine and catheters, T. asahii was the
      species most commonly isolated (76.5%; n =23), followed by T. inkin (16.6%; n =
      5) and T. asteroides (6.6%; n = 2). In addition, the highest isolation rate
      occurred in subjects in the 71- to 80-year-old age range (36.7%; n= 11), followed
      by 61 to 70 (26.7%; n = 8), 51 to 60 (13.3%; n = 4), 31 to 40 (13.33%; n = 4),
      and 41 to 50 (10%; n =3). We concluded that 6 medically important species of the
      genus Trichosporon colonize the perigenital region in a normal population. The
      identification of these species is possible by means of classical methods but
      often requires repeated analyses repetitions due to difficulties in the
      assimilation process. In contrast, only 3 species of Trichosporon were isolated
      from urine and catheters. 

PMID- 24031539
TI  - An Investigation on in vitro and in vivo Antimicrobial Properties of the
      Antidepressant: Amitriptyline Hydrochloride.
AB  - The antidepressant drug amitriptyline hydrochloride was obtained in a dry powder
      form and was screened against 253 strains of bacteria which included 72 Gram
      positive and 181 Gram negative bacteria and against 5 fungal strains. The minimum
      inhibitory concentration (MIC) was determined by inoculating a loopful of an
      overnight peptone water culture of the organism on nutrient agar plates
      containing increasing concentrations of amitriptyline hydrochloride (0, 10
      MUg/mL, 25 MUg/mL, 50 MUg/mL, 100 MUg/mL, 200 MUg/mL). Amitriptyline
      hydrochloride exhibited significant action against both Gram positive and Gram
      negative bacteria at 25-200 MUg/mL. In the in vivo studies it was seen that
      amitriptyline hydrochloride at a concentration of 25 MUg/g and 30 MUg/g body
      weight of mouse offered significant protection to Swiss strain of white mice when
      challenged with 50 median lethal dose (MLD) of a virulent strain of Salmonella
      typhimurium NCTC 74. The in vivo data were highly significant (p<0.001) according
      to the chi-square test. 

PMID- 24031540
TI  - Bacteriocins produced by L. Fermentum and L. Acidophilus can inhibit
      cephalosporin resistant e. Coli.
AB  - Reemerging infections occur due to resistant bacteria. Such infections create
      restrictions for clinicians and microbiologists in drug selection. Such problems
      demand new strategies for solution. Use of bacteriocins for this purpose may be
      fruitful. In the present research work, the inhibitory effects of bactericins on
      cephalosporin resistant Escherichia coli are used as model system for the control
      of antibiotic resistant pathogenic bacteria. Cephalosporin resistant Escherichia
      coli strain was isolated from pus by using conventional methodology. For
      bacteriocin production, Lactobacilli strains were selected by using selective
      media. Out of seventy two strains isolated from yogurt, fecal materials of human,
      chick, parrot and cat, only two strains (strain 45 and strain 52) were found to
      produce bacteriocins having antimicrobial potential against cephalosporin
      resistant Escherichia coli. Biochemical characterization showed that strain 45
      belonged to group of Lactobacillus fermentum and strain 52 to Lactobacillus
      acidophilus. Both strains showed maximum growth at 25 degrees C and 35 degrees C
      respectively. Suitable pH was 5.5 and 6.0 for Lactobacillus fermentum and
      Lactobacillus acidophilus respectively. Bacteriocins produced by both strains
      were found stable at 50, 75 and 100 degrees C for 60min. Function of bacteriocin
      was also not disturbed due to change in pH. These findings suggest that
      bacteriocin produced by Lactobacillus fermentum and Lactobacillus acidophilus can
      be used for the infection control of cephalosporin resistant Escherichia coli. 

PMID- 24031542
TI  - Selection of biosurfactan/bioemulsifier-producing bacteria from hydrocarbon
      contaminated soil.
AB  - Petroleum-derived hydrocarbons are among the most persistent soil contaminants,
      and some hydrocarbon-degrading microorganisms can produce biosurfactants to
      increase bioavailability and degradation. The aim of this work was to identify
      biosurfactant-producing bacterial strains isolated from hydrocarbon-contaminated
      sites, and to evaluate their biosurfactant properties. The drop-collapse method
      and minimal agar added with a layer of combustoleo were used for screening, and
      positive strains were grown in liquid medium, and surface tension and
      emulsification index were determined in cell-free supernantant and cell
      suspension. A total of 324 bacterial strains were tested, and 17 were positive
      for the drop-collapse and hydrocarbon-layer agar methods. Most of the strains
      were Pseudomonas, except for three strains (Acinetobacter, Bacillus,
      Rhodococcus). Surface tension was similar in cell-free and cell suspension
      measurements, with values in the range of 58 to 26 (mN/m), and all formed stable
      emulsions with motor oil (76-93% E24). Considering the variety of molecular
      structures among microbial biosurfactants, they have different chemical
      properties that can be exploited commercially, for applications as diverse as
      bioremediation or degradable detergents. 

PMID- 24031541
TI  - Multiple responses of gram-positive and gram-negative bacteria to mixture of
      hydrocarbons.
AB  - Most of our knowledge about pollutants and the way they are biodegraded in the
      environment has previously been shaped by laboratory studies using hydrocarbon
      degrading bacterial strains isolated from polluted sites. In present study Gram
      positive (Mycobacterium sp. IBBPo1, Oerskovia sp. IBBPo2, Corynebacterium sp.
      IBBPo3) and Gram-negative (Chryseomonas sp. IBBPo7, Pseudomonas sp. IBBPo10,
      Burkholderia sp. IBBPo12) bacteria, isolated from oily sludge, were found to be
      able to tolerate pure and mixture of saturated hydrocarbons, as well as pure and
      mixture of monoaromatic and polyaromatic hydrocarbons. Isolated Gram-negative
      bacteria were more tolerant to mixture of saturated (n-hexane, n-hexadecane,
      cyclohexane), monoaromatic (benzene, toluene, ethylbenzene) and polyaromatic
      (naphthalene, 2-methylnaphthalene, fluorene) hydrocarbons than Gram-positive
      bacteria. There were observed cellular and molecular modifications induced by
      mixture of saturated, monoaromatic and polyaromatic hydrocarbons to Gram-positive
      and Gram-negative bacteria. These modifications differ from one strain to another
      and even for the same bacterial strain, according to the nature of hydrophobic
      substrate. 

PMID- 24031543
TI  - Utilization of rocks and ectomycorrhizal fungi to promote growth of eucalypt.
AB  - The utilization of rocks as fertilizers is limited by their low solubility.
      However, solubilization may be achieved by some micro-organisms, such as
      ectomycorrhizal fungi (ECMf). The aim of this study was to evaluate the potential
      of seven isolates of ECMf to solubilize two rocks, alkaline breccia and granite,
      and to liberate potassium and phosphorus for Eucalyptus dunnii seedlings under
      greenhouse conditions. Fungal inoculants were produced in a peat-vermiculite
      liquid medium mixture and added to the planting substrate at 10 %. Rocks were
      ground up and added at 0.500 mg and 16.0 mg per plant, as a source of phosphorus
      and potassium, respectively. Other nutrients were added and E. dunnii seeds were
      sown. Control plants, non-inoculated, were fertilized with the same amount of
      phosphorus and potassium using soluble forms. After 90 days, the plant height,
      shoot dry weight, root length, phosphorus and potassium contents, and mycorrhizal
      colonization were evaluated. Alkaline breccia was more efficient than granite as
      a source of phosphorus and potassium for the plants, and may be an alternative to
      conventional fertilizers. Isolates UFSC-Pt22 (Pisolithus sp.) and UFSC-Pt186
      (Pisolithus microcarpus) were the most efficient in promoting plant growth,
      mainly when combined with alkaline breccia to replace potassium and phosphorus
      fertilizers, respectively. 

PMID- 24031544
TI  - Biosurfactant production by rhodococcus erythropolis and its application to oil
      removal.
AB  - The influence of different nutrients on biosurfactant production by Rhodococcus
      erythropolis was investigated. Increasing the concentration of phosphate buffer
      from 30 up through 150 mmol/L stimulated an increase in biosurfactant production,
      which reached a maximum concentration of 285 mg/L in shaken flasks. Statistical
      analysis showed that glycerol, NaNO3, MgSO4 and yeast extract had significant
      effects on production. The results were confirmed in a batchwise bioreactor, and
      semi-growth-associated production was detected. Reduction in the surface tension,
      which indicates the presence of biosurfactant, reached a value of 38 mN/m at the
      end of 35 hours. Use of the produced biosurfactant for washing crude oil
      contaminated soil showed that 2 and 4 times the critical micellar concentration
      (CMC) were able to remove 97 and 99% of the oil, respectively, after 1 month of
      impregnation. 

PMID- 24031545
TI  - Aeromonas presence in drinking water from collective reservoirs and wells in peri
      urban area in Brazil.
AB  - Aeromonas genus is considered an emerging pathogen and its presence in drinking
      water supplies is a reason to public health concern. This study investigated the
      occurrence of Aeromonas in samples from collective reservoirs and wells used as
      drinking water sources in a peri-urban area. A total of 35 water samples were
      collected from collective reservoirs and 32 from wells bimonthly, from September
      2007 to September 2008. Aeromonas spp determination was carried out using a
      Multiple-Tube Technique. Samples were inoculated into alkaline peptone water and
      the superficial film formed was transferred to blood agar plates amended with
      ampicillin. Typical Aeromonas colonies were submitted to a biochemical screening
      and then to biochemical tests for species differentiation. Aeromonas was detected
      in 13 (19%) of the 69 samples examined (6 from collective reservoirs and 7 from
      wells). Concentrations of Aeromonas in collective reservoirs ranged from <0.3 to
      1.2 x10(2)MPN/100mL and, in wells, from <0.3 to 2.4 x10(2)MPN/100mL. The most
      frequent specie in the collective reservoir samples was Aeromonas spp (68%),
      followed by A. encheleia (14%) and A. allosaccharophila (8%) and A. hydrophila
      (8%). Aeromonas spp (87%) was the most frequent specie isolated from well
      samples, followed by A. allosacchariphila (8%), A. encheleia (2%) and A. jandaei
      (5%). These data show the presence and diversity of Aeromonas genus in the
      samples analyzed and highlight that its presence in drinking water poses a
      significant public health concern. 

PMID- 24031546
TI  - Study of the interactions between penicillium oxalicum currie & thom and
      alternaria alternata (fr.) keissler.
AB  - The aim of this research was the analysis of the possible antagonistic effect of
      Penicillium oxalicum over the pathogen rice fungus A. alternata under different
      conditions of temperature, water activity and culture media. The macroscopic
      study of the dual growth revealed that according to the Index of Dominance P.
      oxalicum was more competitive that A. alternata at 25 degrees C whereas at 15
      degrees C was this species. Microscopic analysis showed that P. oxalicum was a
      mycoparasite of A. alternata at all conditions tested. The antagonist penetrated
      into A. alternata and disintegrated its conidiophores and conidia. The results
      suggests that P. oxalicum may be a possible biological control agent of the rice
      pathogens in a future. 

PMID- 24031547
TI  - Peptidolytic Microbial Community of Methanogenic Reactors from two Modified Uasbs
      of Brewery Industries.
AB  - We studied the peptide-degrading anaerobic communities of methanogenic reactors
      from two mesophilic full-scale modified upflow anaerobic sludge blanket (UASB)
      reactors treating brewery wastewater in Colombia. Most probable number (MPN)
      counts varied between 7.1 x 10(8) and 6.6 * 10(9) bacteria/g volatile suspended
      solids VSS (Methanogenic Reactor 1) and 7.2 * 10(6) and 6.4 * 10(7) bacteria/g
      (VSS) (Methanogenic Reactor 2). Metabolites detected in the highest positive MPN
      dilutions in both reactors were mostly acetate, propionate, isovalerate and, in
      some cases, negligible concentrations of butyrate. Using the highest positive
      dilutions of MPN counts, 50 dominant strains were isolated from both reactors,
      and 12 strains were selected for sequencing their 16S rRNA gene based on their
      phenotypic characteristics. The small-subunit rRNA gene sequences indicated that
      these strains were affiliated to the families Propionibacteriaceae,
      Clostridiaceae and Syntrophomonadaceae in the low G + C gram-positive group and
      Desulfovibrio spp. in the class delta-Proteobacteria. The main metabolites
      detected in the highest positive dilutions of MPN and the presence of
      Syntrophomonadaceae indicate the effect of the syntrophic associations on the
      bioconversion of these substrates in methanogenic reactors. Additionally, the
      potential utilization of external electron acceptors for the complete degradation
      of amino acids by Clostridium strains confirms the relevance of these acceptors
      in the transformation of peptides and amino acids in these systems. 

PMID- 24031548
TI  - Presence of bla TEM-116 Gene in Environmental Isolates of Aeromonas Hydrophila
      and Aeromonas Jandaei from Brazil.
AB  - It is known that Aeromonas spp. possess different chromosomal beta-lactamase
      genes. Presence and phenotypic expression of bla TEM, bla SHV, and bla CTX-M ESBL
      encoding genes were investigated in environmental water isolates of Aeromonas
      hydrophila and Aeromonas jandaei. Presence of bla SHV and bla CTX-M genes was not
      observed, and bla TEM gene was verified in 91% of the isolates. Sequencing of 10
      fragments showed the occurrence of bla TEM-116. 

PMID- 24031549
TI  - Variability of the conserved v3 loop tip motif in hiv-1 subtype B isolates
      collected from brazilian and French patients.
AB  - The diversity of the V3 loop tip motif sequences of HIV-1 subtype B was analyzed
      in patients from Botucatu (Brazil) and Montpellier (France). Overall, 37
      tetrameric tip motifs were identified, 28 and 17 of them being recognized in
      Brazilian and French patients, respectively. The GPGR (P) motif was predominant
      in French but not in Brazilian patients (53.5% vs 31.0%), whereas the GWGR (W)
      motif was frequent in Brazilian patients (23.0%) and absent in French patients.
      Three tip motif groups were considered: P, W, and non-P non-W groups. The
      distribution of HIV-1 isolates into the three groups was significantly different
      between isolates from Botucatu and from Montpellier (P < 0.001). A higher
      proportion of CXCR4-using HIV-1 (X4 variants) was observed in the non-P non-W
      group as compared with the P group (37.5% vs 19.1%), and no X4 variant was
      identified in the W group (P < 0.001). The higher proportion of X4 variants in
      the non-P non-W group was essentially observed among the patients from
      Montpellier, who have been infected with HIV-1 for a longer period of time than
      those from Botucatu. Among patients from Montpellier, CD4+ cell counts were lower
      in patients belonging to the non-P non-W group than in those belonging to the P
      group (24 cells/MUL vs 197 cells/MUL; P = 0.005). Taken together, the results
      suggest that variability of the V3 loop tip motif may be related to HIV-1
      coreceptor usage and to disease progression. However, as analyzed by a
      bioinformatic method, the substitution of the V3 loop tip motif of the subtype B
      consensus sequence with the different tip motifs identified in the present study
      was not sufficient to induce a change in HIV-1 coreceptor usage. 

PMID- 24031550
TI  - Expression of FLJB:Z66 on a Linear Plasmid of Salmonella Enterica Serovar Typhi
      is Dependent on FLIA and FLHDC and Regulated By OMPR.
AB  - Salmonella enterica serovar Typhi z66-positive strains have two different
      flagellin genes, fliC:d/j and fljB:z66, located on the chromosome and on a linear
      plasmid, respectively. To investigate the mechanism underlying the expressional
      regulation of fljB:z66, gene deletion mutants of the regulators FliA, FlhDC, and
      OmpR were constructed in this study. The expression levels of fliC and fljB:z66
      were analyzed by qRT-PCR in the wild-type strain and mutants at high and low
      osmolarity. The results show that the expression levels of both fljB:z66 and fliC
      were greatly reduced in fliA and flhDC mutants under both high and low osmotic
      conditions. In the ompR mutant, the expression levels of fljB:z66, fliC, fliA,
      and flhD were increased at low osmotic conditions. SDS-PAGE and western blotting
      analysis of the secreted proteins revealed that the FljB:z66 was almost absent in
      the fliA and flhDC mutants at both high and low osmolarity. In the wild-type
      strain, the fljB:z66 was more highly expressed under high-osmolarity conditions
      than under low-osmolarity conditions. However, this difference in expression
      disappeared in the ompR mutant. Translational expression assay of FljB:z66 showed
      that the FljB:z66 expression was decreased in ompR mutant at both low and high
      osmolarity. These results suggest that the expression of fljB:z66 in S. enterica
      serovar Typhi is dependent on FliA and FlihDC, and OmpR can regulate the
      expression and secretion of FljB:z66 in different osmolarity. 

PMID- 24031551
TI  - Aflp analysis of xanthomonas axonopodis and x. Arboricola strains used in xanthan
      production studies reveal high levels of polymorphism.
AB  - Amplified fragment length polymorphism (AFLP) was used to analyze the genetic
      diversity of 14 strains of Xanthomonas arboricola pv. pruni and seven strains of
      X. axonopodis pv. phaseoli, which are used in xanthan production studies.
      Relationships identified by the AFLP profiles were assessed for xanthan
      production capacity, geographical location and host plant. Strains were isolated
      from 10 different geographic regions in South and Southeast States in Brazil.
      Data were analyzed for genetic similarity using the Dice coefficient and
      subjected to UPGMA cluster analysis. A total of 128 AFLP fragments were generated
      from four primer combinations: EcoRI+C/MseI+0, EcoRI+A/MseI+0, EcoRI+G/MseI+T and
      EcoRI+G/MseI+A. Of these, 96.1% were polymorphic. X. axonopodis pv. phaseoli (SD
      = 0.27) was shown to be more polymorphic than X. arboricola pv. pruni (SD =
      0.58). All 14 pathovar pruni strains were included in a single main group (SD =
      0.58), while the pathovar phaseoli strains were divided into three separate
      groups, with one group containing five strains (SD = 0.38) and two isolated
      groups (SD = 0.31 and 0.27) composed of only one strain each. Species were
      distinguished by three and eight specific AFLP markers present in the pathovar
      phaseoli and the pathovar pruni, respectively. For the unique strain without
      xanthan production capacity (X. axonopodis pv. phaseoli str. 48), nine specific
      AFLP bands were found. There was no evidence that geographic area or host plant
      influenced genetic heterogeneity. Correlations between AFLP patterns and xanthan
      production capacity were found in some strains, but were not consistent enough to
      establish a relationship. 

PMID- 24031552
TI  - Human papillomavirus infection in women from tlaxcala, Mexico.
AB  - Cervical cancer is an important health problem in women living in developing
      countries. Infection with some genotypes of human papillomavirus (HPV) is the
      most important risk factor associated with cervical cancer. Little information
      exists about HPV genotype distribution in rural and suburban regions of Mexico.
      Thus, we determined the prevalence of HPV genotypes in women from Tlaxcala, one
      of the poorest states in central Mexico, and we evaluated age infection
      prevalence and risk factors associated with cervical neoplasm. A cross-sectional
      study was conducted in 236 women seeking gynecological care at the Mexican
      Institute for Social Security in Tlaxcala, Mexico. Cervical scrapings were
      diagnosed as normal, low-grade, and high-grade squamous intraepithelial lesions
      (LGSIL, HGSIL). Parallel samples were used to detect HPV genotypes by PCR assays
      using type-specific primers for HPV 6, 11, 16, 18, and 31. An epidemiological
      questionnaire was applied. Prevalence of HPV infection was 31.3%. From the
      infected samples, prevalence of HPV 16 was 45.9%; HPV 18, 31.1%; HPV 31, 16.2%;
      HPV 6, 10.8%; HPV 11, 6.7%. With regard to age, the highest HPV prevalence
      (43.5%) was found in the 18- to 24-year-old group and the lowest (19%) in the 45-
      to 54-year-old group. None of the risk factors showed association with cervical
      neoplasia grade. HPV 16 was the most common in cervical lesions. HPV was present
      in 22% of normal samples and, of these, 82.6% represented high-risk HPVs.
      Tlaxcala showed HPV prevalence comparable to that of the largest cities in
      Mexico, with higher prevalence for HPV 31. 

PMID- 24031553
TI  - Production of Angkak Through Co-Culture of Monascus Purpureus and MONASCUS RUBER.
AB  - Angkak (red mold rice, red yeast rice, Chinese red rice) is a traditional Chinese
      medicine produced by solid-state fermentation of cooked non-glutinous rice with
      Monascus species. The secondary metabolite of Monascus species, monacolin K
      /lovastatin, has been proven to lower blood lipid levels. In this study, a co
      culture of Monascus purpureus MTCC 369 and Monascus ruber MTCC 1880 was used for
      angkak production. Four medium parameters screened by Plackett-Burman design were
      optimized by response surface methodology for highest lovastatin production in
      angkak during solid-state fermentation by the co-culture. Maximum lovastatin
      production of 2.84 mg g(-1) was predicted in solid medium containing 20 g rice
      and 40 ml liquid nutrients medium (malt extract 9.68 g l(-1), dextrose 38.90 g l(
      1), MnSO4.H2O 1.96 g l(-1), and MgSO4.7H2O 0.730 g l(-1)) by point prediction
      tool of Design Expert 7.1 software (Statease Inc. USA). 

PMID- 24031554
TI  - Assay of antioxidant potential of two Aspergillus isolates by different methods
      under various physio-chemical conditions.
AB  - The objective of this work was to screen fungi isolated from soil of different
      areas of Punjab, India for antioxidant activity by dot blot assay and around 45%
      of fungal isolates demonstrated antioxidant potential. Two selected strains of
      Aspergillus spp (Aspergillus PR78 and Aspergillus PR66) showing quantitatively
      best antioxidant activity by DPPH assay were further tested for their reducing
      power, ferrous ion and nitric oxide ion scavenging activity, FRAP assay and total
      phenolic content. Different physio-chemical parameters were optimized for
      enhancement of the activity. This revealed stationary culture grown for 10 days
      at 25 (o)C at pH 7 to be the best for antioxidant activity. Sucrose in the medium
      as carbon source resulted in highest antioxidant activity. Sodium nitrate, yeast
      extract, and peptone were good sources of nitrogen but sodium nitrate was the
      best among these. The extraction of the broth culture filtrates with different
      solvents revealed ethyl acetate extract to possess the best antioxidant activity.
      The activity as expressed by ethyl acetate extract of Aspergillus PR78 was
      equally effective as that of commonly used antioxidant standard, ascorbic acid. 

PMID- 24031555
TI  - Hyperexpression of two Aspergillus Niger Xylanase Genes in Escherichia Coli and
      Characterization of the Gene Products.
AB  - The analysis of individual gene product should enable to clarify the role of a
      particular enzyme in a complex xylanase system of A. niger. The two genes
      encoding precursors of co-produced endo-1,4-beta-D-xylanases, xynA1 and xynB,
      were isolated from Aspergillus niger SCTCC 400264 (SCTCC, China) by using RT-PCR
      technique and then successfully expressed in Escherichia coli BL21. The
      nucleotide sequences of the xynA1 and xynB genes revealed that they were only
      52.5% homology to each other. Characterization of the recombinant enzymes
      revealed the different properties: the specific activity of recombinant XYNA1 was
      16.58 U/mg compared to 1201.7 U/mg for recombinant XYNB; The optimum temperature
      and pH of the recombinant XYNA1 were 35  degrees C and 3.0, respectively, whereas
      the corresponding values for the recombinant XYNB were 55  degrees C and 5.0,
      respectively; The recombinant XYNB showed much more thermostability than
      recombinant XYNA1; The recombinant XYNB showed 94% of maximal activity after
      incubating in water for 60 min at 60  degrees C compared to no activity for
      recombinant XYNA1. Various metal ions had different effects on activity between
      the two recombinant xylanases. 

PMID- 24031556
TI  - Phosphate solubilization potential and phosphatase activity of rhizospheric
      trichoderma spp.
AB  - Trichoderma sp., a well known biological control agent against several
      phytopathogens, was tested for its phosphate (P) solubilizing potential. Fourteen
      strains of Trichoderma sp. were isolated from the forest tree rhizospheres of
      pinus, deodar, bamboo, guava and oak on Trichoderma selective medium. The
      isolates were tested for their in-vitro P-solubilizing potential using National
      Botanical Research Institute Phosphate (NBRIP) broth containing tricalcium
      phosphate (TCP) as the sole P source, and compared with a standard culture of T.
      harzianum. All the cultures were found to solubilize TCP but with varying
      potential. The isolate DRT-1 showed maximum amount of soluble phosphate (404.07
      epsilong.ml(-1)), followed by the standard culture of T. harzianum (386.42
      epsilong.ml(-1)) after 96 h of incubation at 30+/-1(0)C. Extra-cellular acid and
      alkaline phosphatases of the fungus were induced only in the presence of
      insoluble phosphorus source (TCP). High extra-cellular alkaline phosphatase
      activity was recorded for the isolate DRT-1 (14.50 U.ml(-1)) followed by the
      standard culture (13.41 U.ml(-1)) at 72h. The cultures showed much lesser acid
      phosphatase activities. Under glasshouse conditions, Trichoderma sp. inoculation
      increased chickpea (Cicer arietinum) growth parameters including shoot length,
      root length, fresh and dry weight of shoot as well as roots, in P-deficient soil
      containing only bound phosphate (TCP). Shoot weight was increased by 23% and 33%
      by inoculation with the isolate DRT-1 in the soil amended with 100 and 200 mg TCP
      kg(-1) soil, respectively, after 60 d of sowing. The study explores high P
      solubilizing potential of Trichoderma sp., which can be exploited for the
      solubilization of fixed phosphates present in the soil, thereby enhancing soil
      fertility and plant growth. 

PMID- 24031557
TI  - Isolation and Purification of Complex II from Proteus Mirabilis Strain ATCC
      29245.
AB  - A respiratory complex was isolated from plasma membrane of pathogenic Proteus
      mirabilis strain ATCC 29245. It was identified as complex II consisting of
      succinate:quinone oxidoreductase (EC 1.3.5.1) containing single heme b. The
      complex II was purified by ion-exchange chromatography and gel filtration. The
      molecular weight of purified complex was 116.5 kDa and it was composed of three
      subunits with molecular weights of 19 kDa, 29 kDa and 68.5 kDa. The complex II
      contained 9.5 nmoles of cytochrome b per mg protein. Heme staining indicated that
      the 19 kDa subunit was cytochrome b. Its reduced form showed absorptions peaks at
      557.0, 524.8 and 424.4 nm. The alpha-band was shifted from 557.0 nm to 556.8 nm
      in pyridine ferrohemochrome spectrum. The succinate: quinone oxidoreductase
      activity was found to be high in this microorganism. 

PMID- 24031558
TI  - Mechanism of bactericidal activity of silver nitrate - a concentration dependent
      bi-functional molecule.
AB  - Silver nitrate imparts different functions on bacteria depending upon its
      concentration. At lower concentration it induced synthesis of nanoparticles,
      whereas at higher concentrations it induced cell death. Bacillus licheniformis
      was used as model system. The MIC was 5 mM, and it induced catalase production,
      apoptotic body formation and DNA fragmentation. 

PMID- 24031559
TI  - Differentiation of bovine coronavirus (bcov) genotypes by a restriction enzyme
      assay.
AB  - This article reports the use of the GsuI restriction enzyme to differentiate
      genotypes of Bovine Coronavirus (BCoV), based on an 18-nucleotide deletion of S1
      coding region found in one of the two genotypes. It was concluded that this assay
      can be used as a rapid tool for BCoV genotypes differentiation. 

PMID- 24031560
TI  - Rickettsia felis infection in cat fleas ctenocephalides felis felis.
AB  - The present study evaluated the rickettsial infection in a laboratory colony of
      cat fleas, Ctenocephalides felis felis (Bouche) in Brazil. All flea samples (30
      eggs, 30 larvae, 30 cocoons, 30 males, and 30 females) tested by polymerase chain
      reaction (PCR) were shown to contain rickettsial DNA. PCR products, corresponding
      to the rickettsial gltA, htrA, ompA and ompB gene partial sequences were
      sequenced and showed to correspond to Rickettsia felis, indicating that the flea
      colony was 100% infected by R. felis. The immunofluorescence assay (IFA) showed
      the presence of R. felis-reactive antibodies in blood sera of 7 (87.5%) out of 8
      cats that were regularly used to feed the flea colony. From 15 humans that used
      to work with the flea colony in the laboratory, 6 (40.0%) reacted positively to
      R. felis by IFA. Reactive feline and human sera showed low endpoint titers
      against R. felis, varying from 64 to 256. With the exception of one human serum,
      all R. felis-reactive sera were also reactive to Rickettsia rickettsii and/or
      Rickettsia parkeri antigens at similar titers to R. felis. The single human serum
      that was reactive solely to R. felis had an endpoint titer of 256, indicating
      that this person was infected by R. felis. 

PMID- 24031561
TI  - Glucuronidase activity of Escherichia coli isolated from chicken carcasses.
AB  - To identify Escherichia coli through the production of beta-D-glucuronidase
      (GUD), 622 suspect cultures were isolated from chicken carcasses and plated in
      PetrifilmTM EC. Of these cultures, only 44 (7.1%) failed to produce GUD. This
      result indicates the usefulness of GUD production for estimating E. coli
      populations in chicken. 

PMID- 24031562
TI  - Conventional and alternative antifungal therapies to oral candidiasis.
AB  - Candida-associated denture stomatitis is the most common form of oral candidal
      infection, with Candida albicans being the principal etiological agent. Candida
      adheres directly or via an intermediary layer of plaque-forming bacteria to
      denture acrylic. Despite antifungal therapy to treat denture stomatitis,
      infection is reestablished soon after the treatment ceases. In addition, many
      predisposing factors have been identified as important in the development of oral
      candidiasis, including malnourishment, common endocrine disorders, such as
      diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and
      other immunocompromised conditions, such as acquired immunodeficiency syndrome
      (AIDS). These often results in increased tolerance to the most commonly used
      antifungals. So this review suggests new therapies to oral candidiasis. 

PMID- 24031563
TI  - The role of mycorrhization helper bacteria in the establishment and action of
      ectomycorrhizae associations.
AB  - More than 95 % short roots of most terrestrial plants are colonized by
      mycorrhizal fungi as soon as they emerge in the upper soil profiles. The
      establishment of mycorrhizal association involves profound morphological and
      physiological changes in root and fungus. It is affected by other rhizospheric
      microorganisms, specifically by the bacteria. Bacteria may have developed
      mechanisms of selective interaction with surrounding microorganisms, with neutral
      or positive effects on mycorrhizal associations, but negative effect on root
      pathogens in general. Because of the beneficial effect of bacteria on
      mycorrhizae, the concept of Mycorrhization Helper Bacteria (MHB) was created.
      Five main actions of MHB on mycorrhizae were proposed: in the receptivity of root
      to the mycobiont, in root-fungus recognition, in fungal growth, in the
      modification of rhizospheric soil and in the germination of fungal propagules.
      MHB appear to develop a gradation of specificity for the mycobiont, but little or
      no specificity for the host plant in symbiosis. One of the main groups of MHB is
      the fluorescent Pseudomonas, well represented in diversity and cell density
      studies of mycorrhizal associations. This review covers the activity of MHB in
      the establishment of ectomycorrhizae, taking as model the effects of Pseudomonas
      sp. described in scientific literature. 

PMID- 24031564
TI  - Candida albicans: genotyping methods and clade related phenotypic
      characteristics.
AB  - Several molecular methods, such as Southern blotting hybridization, Multilocus
      Sequence Typing, and DNA microsatellite analysis, have been employed to genotype
      Candida albicans. The genotype analysis allows to group strains in clades, that
      is, a group composed of one ancestor and its descendants. These genotype studies
      demonstrate that clades distribution is influenced by geographic area as well as
      that antifungal resistance is associated with particular clades. These findings
      suggested that C. albicans reproduces mainly in a clonal manner, with certain
      degree of DNA microevolution. Additionally, virulence factors and site of
      isolation have also been associated with clade specificity. The present article
      is a brief review about the methods used for Candida genotyping and the
      correlated clade systems established. Special emphasis is given to Ca3
      hybridization, MLST, and Microsatellites. The present work is also focused on the
      phenotypic and physiological traits associated with Candida clades. 

PMID- 24031565
TI  - Application of microbial alpha-amylase in industry - A review.
AB  - Amylases are one of the main enzymes used in industry. Such enzymes hydrolyze the
      starch molecules into polymers composed of glucose units. Amylases have potential
      application in a wide number of industrial processes such as food, fermentation
      and pharmaceutical industries. alpha-Amylases can be obtained from plants,
      animals and microorganisms. However, enzymes from fungal and bacterial sources
      have dominated applications in industrial sectors. The production of alpha
      amylase is essential for conversion of starches into oligosaccharides. Starch is
      an important constituent of the human diet and is a major storage product of many
      economically important crops such as wheat, rice, maize, tapioca, and potato.
      Starch-converting enzymes are used in the production of maltodextrin, modified
      starches, or glucose and fructose syrups. A large number of microbial alpha
      amylases has applications in different industrial sectors such as food, textile,
      paper and detergent industries. The production of alpha-amylases has generally
      been carried out using submerged fermentation, but solid state fermentation
      systems appear as a promising technology. The properties of each alpha-amylase
      such as thermostability, pH profile, pH stability, and Ca-independency are
      important in the development of fermentation process. This review focuses on the
      production of bacterial and fungal alpha-amylases, their distribution, structural
      functional aspects, physical and chemical parameters, and the use of these
      enzymes in industrial applications. 

PMID- 24031566
TI  - Biotechnological production of citric acid.
AB  - This work provides a review about the biotechnological production of citric acid
      starting from the physicochemical properties and industrial applications, mainly
      in the food and pharmaceutical sectors. Several factors affecting citric acid
      fermentation are discussed, including carbon source, nitrogen and phosphate
      limitations, pH of culture medium, aeration, trace elements and morphology of the
      fungus. Special attention is paid to the fundamentals of biochemistry and
      accumulation of citric acid. Technologies employed at industrial scale such as
      surface or submerged cultures, mainly employing Aspergillus niger, and processes
      carried out with Yarrowia lipolytica, as well as the technology for recovering
      the product are also described. Finally, this review summarizes the use of orange
      peels and other by-products as feedstocks for the bioproduction of citric acid. 

PMID- 24031568
TI  - Distribution of prokaryotic organisms in a tropical estuary influenced by sugar
      cane agriculture in northeast Brazil.
AB  - In a joint Brazilian-German case study, distribution patterns of microorganisms
      were compared with environmental variables in the tropical coastal Manguaba
      lagoon in northeast Brazil, which is situated downstream of several sugar cane
      processing plants . 16S rDNA and 16S rRNA single strand conformation polymorphism
      (SSCP) gene fingerprinting were used to follow the composition and distribution
      of microorganisms throughout the salinity gradient of the lagoon. Potentially
      abundant microorganisms were identified by sequencing representative SSCP bands.
      It could be demonstrated that the distribution of microbes was in close relation
      to the physico-chemical environmental settings and followed a common scheme. In
      the in- and outlet areas of the lagoon rather transient microbial communities
      were found, whereas in the central part a stable, diverse community was
      encountered, that due to the long residence time of the water, had ample time for
      development and adaptation. 

PMID- 24031567
TI  - Molecular cloning, characterization and enzymatic properties of a novel betaeta
      agarase from a marine isolate Psudoalteromonas SP. AG52.
AB  - An agar-degrading Pseudoalteromonas sp. AG52 bacterial strain was identified from
      the red seaweed Gelidium amansii collected from Jeju Island, Korea. A beta
      agarase gene which has 96.8% nucleotide identity to Aeromonas beta-agarase was
      cloned from this strain, and was designated as agaA. The coding region is 870 bp,
      encoding 290 amino acids and possesses characteristic features of the glycoside
      hydrolase family (GHF)-16. The predicted molecular mass of the mature protein was
      32 kDa. The recombinant beta-agarase (rAgaA) was overexpressed in Escherichia
      coli and purified as a fusion protein. The optimal temperature and pH for
      activity were 55  degrees C and 5.5, respectively. The enzyme had a specific
      activity of 105.1 and 79.5 unit/mg toward agar and agarose, respectively. The
      pattern of agar hydrolysis demonstrated that the enzyme is an endo-type beta
      agarase, producing neoagarohexaose and neoagarotetraose as the final main
      products. Since, Pseudoalteromonas sp. AG52 encodes an agaA gene, which has
      greater identity to Aeromonas beta-agarase, the enzyme could be considered as
      novel, with its unique bio chemical characteristics. Altogether, the purified
      rAgaA has potential for use in industrial applications such as development of
      cosmetics and pharmaceuticals. 

PMID- 24031569
TI  - Characterization of Bacillus isolates of potato rhizosphere from andean soils of
      Peru and their potential PGPR characteristics.
AB  - Bacillus spp. are well known rhizosphere residents of many crops and usually show
      plant growth promoting (PGP) activities that include biocontrol capacity against
      some phytopatogenic fungi. Potato crops in the Andean Highlands of Peru face many
      nutritional and phytophatogenic problems that have a significant impact on
      production. In this context is important to investigate the natural presence of
      these microorganisms in the potato rhizosphere and propose a selective screening
      to find promising PGP strains. In this study, sixty three Bacillus strains
      isolated from the rhizosphere of native potato varieties growing in the Andean
      highlands of Peru were screened for in vitro antagonism against Rhizoctonia
      solani and Fusarium solani. A high prevalence (68%) of antagonists against R.
      solani was found. Ninety one percent of those strains also inhibited the growth
      of F. solani. The antagonistic strains were also tested for other plant growth
      promotion activities. Eighty one percent produced some level of the auxin indole
      3-acetic acid, and 58% solubilized tricalcium phosphate. Phylogenetic analysis
      revealed that the majority of the strains belonged to the B. amyloliquefaciens
      species, while strains Bac17M11, Bac20M1 and Bac20M2 may correspond to a putative
      new Bacillus species. The results suggested that the rhizosphere of native
      potatoes growing in their natural habitat in the Andes is a rich source of
      Bacillus fungal antagonists, which have a potential to be used in the future as
      PGP inoculants to improve potato crop. 

PMID- 24031570
TI  - Role of brown-rot fungi in the bioremoval of azo dyes under different conditions.
AB  - The present study is vital to the understanding of bioremediation of structurally
      different azo dyes by some unusual Brown-rot fungi. Bioremoval of each dye (20 mg
      l(-1)) was tested in two different culture media under static and shaking
      conditions by taking inocula from different fungi. Fungal strains showed varying
      dyes removal abilities, though considerable high in case of Acid Red (AR) 151(di
      azo) as compared to Orange (Or) II (mono-azo). With an exception of Aspergillus
      tereus SA3, all the fungal isolates showed higher removal of dyes in SDB. Under
      static condition, the maximum decolorizing fungal strains were; Aspergillus
      flavus SA2 (67%) and Alternaria spp. SA4 (57%) in AR 151, while Penicillium spp.
      (34 and 33 %) in Orange II, in SDB and STE, respectively. Bioremoval of dyes was
      considerably increased when experiments were shifted from static to shaking mode.
      It was specifically increased (%) in; AR 151 (255) with Penicillium spp., Or II
      with A. flavus SA2 (112) and Alternaria spp. (111). The primary mechanism of dyes
      removal proved to be fungal biosorption. However, reduction of dyes (onto fungal)
      with formation of their products (alpha. naphthol, sulphalinic acid and aniline)
      furthermore revealed that dyes (specifically azo) were actually biodegraded. 

PMID- 24031571
TI  - Isolation and characteristics of lactic acid bacteria isolated from ripe
      mulberries in Taiwan.
AB  - The objective of this study was to isolate, characterize, and identify lactic
      acid bacteria (LAB) from ripe mulberries collected in Taiwan. Ripe mulberry
      samples were collected at five mulberry farms, located in different counties of
      Taiwan. Eighty-eight acid-producing cultures were isolated from these samples,
      and isolates were divided into classes first by phenotype, then into groups by
      restriction fragment length polymorphism (RFLP) analysis and sequencing of 16S
      ribosomal DNA (rDNA). Phenotypic and biochemical characteristics led to
      identification of four bacterial groups (A to D). Weissella cibaria was the most
      abundant type of LAB distributed in four mulberry farms, and Lactobacillus
      plantarum was the most abundant LAB found in the remaining farm. Ten W. cibaria
      and one Lactococcus lactis subsp. lactis isolate produced bacteriocins against
      the indicator strain Lactobacillus sakei JCM 1157(T). These results suggest that
      various LAB are distributed in ripe mulberries and W. cibaria was the most
      abundant LAB found in this study. 

PMID- 24031572
TI  - Biodegradation of naphthalene and anthracene by chemo-tactically active
      rhizobacteria of populus deltoides.
AB  - Several naphthalene and anthracene degrading bacteria were isolated from
      rhizosphere of Populus deltoides, which were growing in non-contaminated soil.
      Among these, four isolates, i.e. Kurthia sp., Micrococcus varians, Deinococcus
      radiodurans and Bacillus circulans utilized chrysene, benzene, toluene and
      xylene, in addition to anthracene and naphthalene. Kurthia sp and B. circulans
      showed positive chemotactic response for naphthalene and anthracene. The mean
      growth rate constant (K) of isolates were found to increase with successive
      increase in substrate concentration (0.5 to 1.0 mg/50ml). B. circulans SBA12 and
      Kurthia SBA4 degraded 87.5% and 86.6% of anthracene while, Kurthia sp. SBA4, B.
      circulans SBA12, and M. varians SBA8 degraded 85.3 %, 95.8 % and 86.8 % of
      naphthalene respectively after 6 days of incubation as determined by HPLC
      analysis. 

PMID- 24031573
TI  - Degradation of h-acid by free and immobilized cells of Alcaligenes latus.
AB  - Alcaligenes latus, isolated from industrial effluent, was able to grow in mineral
      salts medium with 50 ppm (0.15 mM) of H-acid as a sole source of carbon.
      Immobilization of Alcaligenes latus in Ca-alginate and polyurethane foam resulted
      in cells embedded in the matrices. When free cells and immobilized cells were
      used for biodegradation studies at concentration ranging from 100 ppm (0.3 mM) to
      500 ppm (1.15 mM) degradation rate was enhanced with immobilized cells. Cells
      immobilized in polyurethane foam showed 100% degradation up to 350 ppm (1.05 mM)
      and 57% degradation at 500 ppm (1.5 mM). Degradation rate of Ca-alginate
      immobilized cells was less as compared to that of polyurethane foam immobilized
      cells. With Ca-alginate immobilized cells 100% degradation was recorded up to 200
      ppm (0.6 mM) of H-acid and only 33% degradation was recorded at 500 ppm (1.5 mM)
      of H-acid. Spectral analysis of the products after H-acid utilization showed that
      the spent medium did not contain any aromatic compounds indicating H-acid
      degradation by A. latus. 

PMID- 24031574
TI  - Comparative study of wild and transformed salt tolerant bacterial strains on
      Triticum aestivum growth under salt stress.
AB  - Eleven salt tolerant bacteria isolated from different sources (soil, plants) and
      their transformed strains were used to study their influence on Triticum aestivum
      var. Inqlab-91 growth under salt (100 mM NaCl) stress. Salt stress caused
      reduction in germination (19.4%), seedling growth (46%) and fresh weight (39%) in
      non-inoculated plants. In general, both wild and transformed strains stimulated
      germination, seedling growth and fresh weight in salt free and salt stressed
      conditions. At 100 mM NaCl, Staphylococcus xylosus ST-1 caused 25% increments in
      seedling length over respective control. Soluble protein content significantly
      enhanced (49%) under salt stress as compared to salt free control. At 100 mM NaCl
      parental strain PT-5 resulted about 32% enhancement in protein content over
      respective control treatment. Salt stress induced the promotion of auxin content
      in seedlings. Overall, Bacillus subtilis HAa2 and transformed E. coli -SP-7-T,
      caused 33% and 30% increases in auxin content, respectively, were recorded under
      salt stress in comparison to control. 

PMID- 24031575
TI  - The effect of different growth regimes on the endophytic bacterial communities of
      the fern, Dicksonia sellowiana hook (Dicksoniaceae).
AB  - Endophytic bacteria associated with the fern Dicksonia sellowiana were
      investigated. The bacterial communities from the surface-sterilized pinnae and
      rachis segments of the plants from the Brazilian Atlantic Rainforest that grew in
      native field conditions were compared with the bacterial communities from plants
      grown in greenhouses and plants that were initially grown in greenhouses and then
      transferred to the forest. From 540 pinnae and 540 rachis segments, 163 (30.2%)
      and 346 (64.2%) were colonized by bacteria, respectively. The main bacterial
      genera and species that were isolated included Bacillus spp. ( B. cereus, B.
      megaterium, B. pumilus and B. subtilis ) , Paenibacillus sp. , Amphibacillus sp.
      , Gracilibacillus sp. , Micrococcus sp. and Stenotrophomonas spp. ( S.
      maltophilia and S. nitroreducens ). B. pumilus was the most frequently isolated
      bacterial species . Amphibacillus and Gracilibacillus were reported as endophytes
      for the first time. Other commonly found bacterial genera were not observed in D.
      sellowiana , which may reflect preferences of specific bacterial communities
      inside this fern or detection limitations due to the isolation procedures. Plants
      that were grown in greenhouses and plants that were reintroduced into the forest
      displayed more bacterial genera and species diversity than native field plants,
      suggesting that reintroduction shifts the bacterial diversity. Endophytic
      bacteria that displayed antagonistic properties against different microorganisms
      were detected, but no obvious correlation was found between their frequencies
      with plant tissues or with plants from different growth regimes. This paper
      reports the first isolation of endophytic bacteria from a fern. 

PMID- 24031576
TI  - Antimicrobial resistance and PCR-ribotyping of Shigella responsible for foodborne
      outbreaks occurred in southern Brazil.
AB  - Little information about Shigella responsible for foodborne shigellosis is
      available in Brazil. The present study aimed to investigate the antimicrobial
      resistance and PCR-ribotyping patterns of Shigella isolates responsible for
      foodborne outbreaks occurred in Rio Grande do Sul State (RS), Southern Brazil in
      the period between 2003 and 2007. Shigella strains (n=152) were isolated from
      foods and fecal samples of victims of shigellosis outbreaks investigated by the
      Surveillance Service. Identification of the strains at specie level indicated
      that 71.1% of them were S. flexneri, 21.5% S. sonnei, and 0.7% S. dysenteriae.
      Ten strains (6.7%) were identified only as Shigella spp. An increasing occurrence
      of S. sonnei was observed after 2004. Most of the strains were resistant to
      streptomycin (88.6%), followed by ampicillin (84.6%), and
      sulfamethoxazole/trimethoprim (80.5 %). Resistant strains belonged to 73
      patterns, and pattern A (resistance to ampicillin, sulfamethoxazole/trimethoprim,
      tetracycline, streptomycin, chloramphenicol, and intermediate resistance to
      kanamycin) grouped the largest number of isolates (n=36). PCR-ribotyping
      identified three banding patterns (SH1, SH2, and SH3). SH1 grouped all S.
      flexneri and SH2 grouped all S. sonnei. The S. dysenteriae strain belonged to
      group SH3. According to the results, several Shigella isolates shared the same
      PCR-rybotyping banding pattern and the same resistance profile, suggesting that
      closely related strains were responsible for the outbreaks. However, other
      molecular typing methods need to be applied to confirm the clonal relationship of
      these isolates. 

PMID- 24031577
TI  - Virulence and cytotoxicity of seafood borne Aeromonas hydrophila.
AB  - The present study was conducted to determine the virulence and cytotoxicity of
      Aeromonas hydrophila strains isolated from seafood samples collected from 5 major
      fish markets in Chennai, Tamil Nadu, India. Among 73 A. hydrophila strains
      isolated from fish and shrimp samples, 86.3% exhibited haemolysis, 78.1% produced
      slime, 98.63% produced protease and also demonstrated cytotoxicity on Vero cells.
      Cell shrinkage, detachment and rounding of Vero cells were recorded as cytotoxic
      changes. Only one strain did not show haemolysis, slime production, proteolytic
      activity and cytotoxicity on treatment with Vero cells. Positive correlation was
      observed between proteolytic activity and cytotoxicity irrespective of haemolytic
      activity of the strains. These results demonstrated the presence of wide spread,
      pathogenically characterized, cytotoxic seafood borne A. hydrophila in Chennai. 

PMID- 24031578
TI  - Assessment of hydrophobicity and roughness of stainless steel adhered by an
      isolate of Bacillus cereus from a dairy plant.
AB  - The interaction between the surface of stainless steel and Bacillus cereus was
      studied in terms of the characteristics of interfacial interaction determined
      from the measurement of the contact angle of the surface of B. cereus and
      stainless steel in the presence or absence of B. cereus adherence. The
      microtopographies and the roughness of the surface of stainless steel and
      stainless steel adhered by B. cereus were evaluated with the help of atomic force
      microscopy and perfilometry. The strain of B. cereus studied was considered
      hydrophilic, whereas the stainless steel was considered hydrophobic. The adhesion
      was not thermodynamically favorable (DeltaGadhesion > 0) between the stainless
      steel and the strain of B. cereus studied. Thus, the interaction between them was
      not favored by the thermodynamic aspect of adhesion. There was no difference (p >
      0.05) in the roughness of the surfaces of stainless steel adhered by B. cereus
      when analyzed by atomic force microscope and perfilometry. 

PMID- 24031579
TI  - Detection of shigella in lettuce by the use of a rapid molecular assay with
      increased sensitivity.
AB  - A Multiplex Polymerase Chain Reaction (PCR) assay to be used as an alternative to
      the conventional culture method in detecting Shigella and enteroinvasive
      Escherichia coli (EIEC) virulence genes ipaH and ial in lettuce was developed.
      Efficacy and rapidity of the molecular method were determined as compared to the
      conventional culture. Lettuce samples were inoculated with different Shigella
      flexneri concentrations (from 10 CFU/ml to 10(7) CFU/ml). DNA was extracted
      directly from lettuce after inoculation (direct-PCR) and after an enrichment step
      (enrichment PCR). Multiplex PCR detection limit was 10(4)CFU/ml, diagnostic
      sensitivity and specificity were 100% accurate. An internal amplification control
      (IAC) of 100 bp was used in order to avoid false negative results. This method
      produced results in 1 to 2 days while the conventional culture method required 5
      to 6 days. Also, the culture method detection limit was 10(6) CFU/ml, diagnostic
      sensitivity was 53% and diagnostic specificity was 100%. In this study a
      Multiplex PCR method for detection of virulence genes in Shigella and EIEC was
      shown to be effective in terms of diagnostic sensitivity, detection limit and
      amount of time as compared to Shigella conventional culture. 

PMID- 24031580
TI  - Incorporation of nisin in natural casing for the control of spoilage
      microorganisms in vacuum packaged sausage.
AB  - This study aimed to evaluate the effectiveness of natural casing treatment with
      nisin and phosphoric acid on control of spoilage microorganisms in vacuum
      packaged sausages. Ovine casings were dipped in the following baths: 1) 0.1% food
      grade phosphoric acid; 2) 5.0 mg/L nisin; 3) 0.1% phosphoric acid and 5.0 mg/L
      nisin; and 4) sterile water (control). The sausages were produced in a pilot
      plant, stuffed into the pretreated natural casings, vacuum packaged and stored at
      4 and 10  degrees C for 56 days. The experiments were performed according to a
      full factorial design 2(3), totalizing 8 treatments that were repeated in 3
      blocks. Aerobic plate counts and lactic acid bacteria analysis were conducted at
      1, 14, 28, 42 and 56 days of storage. Treatment of casings with phosphoric acid
      0.1% alone did not inhibit the growth of lactic acid bacteria and reduced the
      aerobic plate count by 1 log. The activity of nisin against lactic acid bacteria
      was enhanced by the addition of phosphoric acid, demonstrating a synergistic
      effect. Furthermore nisin activity was more evident at lower storage temperature
      (4 oC). Therefore treatment of the natural casings with nisin and phosphoric
      acid, combined with low storage temperature, are obstacles that present a
      potential for controlling the growth of lactic acid bacteria in vacuum packaged
      sausage. 

PMID- 24031581
TI  - Production of bacteriocin-like substances by lactic acid bacteria isolated from
      regional ovine cheese.
AB  - Lactic acid bacteria (LAB) were isolated from ovine milk and cheeses manufactured
      in the South Region of Brazil. Among 112 bacterial isolates investigated, 59 were
      chosen through a screening for LAB. Among these 59 strains of LAB, 21% showed
      antimicrobial, proteolytic and lipolytic activities. Based on this screening,
      Lactobacillus plantarum LCN 17 and Lactobacillus rhamnosus LCN 43 were selected
      and tested for the production of bacteriocin-like substances (BLS). The BLS
      produced by both isolates showed antimicrobial activity against Listeria
      monocytogenes, whereas that produced by L. plantarum LCN 17 presented higher
      stability to different temperature, pH and enzyme treatments. These strains
      present potential for production of BLS, and for use as starter cultures. 

PMID- 24031582
TI  - Inhibition of mycotoxin-producing Aspergillus nomius vsc 23 by lactic acid
      bacteria and Saccharomyces cerevisiae.
AB  - The effect of different fermenting microorganisms on growth of a mycotoxin-
      producing Aspergillus nomius was assayed. Two lactic acid bacteria, Lactobacillus
      fermentum and Lactobacillus rhamnosus, and Saccharomyces cerevisiae, all of which
      are widely used in fermentation and preservation of food, were assayed on their
      fungus inhibitory properties. Assays were carried out by simultaneous inoculation
      of one of the possible inhibiting microorganisms and the fungus or subsequent
      inoculation of one of the microorganisms followed by the fungus. All three
      microorganisms assayed showed growth inhibition of the mycotoxin-producing
      Aspergillus strain. L. rhamnosus O236, isolated from sheep milk and selected for
      its technological properties, showed highest fungal inhibition of the
      microorganisms assayed. The use of antifungal LAB with excellent technological
      properties rather than chemical preservatives would enable the food industry to
      produce organic food without addition of chemical substances. 

PMID- 24031583
TI  - Adhesion and biocides inactivation of Salmonella on stainless steel and
      polyethylene.
AB  - The adhesion of Salmonella (S.) strains to stainless steel and polyethylene and
      their inactivation by biocides used in food industry was investigated. Coupons of
      stainless steel and polyethylene were immersed in bacterial suspensions of S.
      Enteritidis, S. Typhimurium, and S. Bredeney during 15, 30, and 60 minutes, and
      submitted to different concentrations of peracetic acid (PAA), sodium
      hypochlorite (NaOCl), and quaternary ammonium (Quat) sanitizers. Hydrophobicity
      of the surfaces was evaluated by contact angle measurements using the sessile
      drop method and bacterial adhesion was accompanied through bacterial counts and
      scanning electron microscopy (SEM). Results indicated that the three serovars of
      Salmonella presented similar adhesion to both materials (5.0 to 6.5 log cfu cm(
      2)). The time of exposure did not influence the counts of adhered cells on both
      surfaces, however SEM revealed larger clusters of S. Enteritidis on both
      materials, not found for the other serovars. S. Enteritidis presented lower
      sessile drop angle on polyethylene, indicating hydrophilic properties of this
      material. The biocides were not able to inactivate all the microorganisms adhered
      on both surfaces. At least 1 log cfu cm(-2) of all serovars tested remained
      viable after the exposure to different biocide concentrations. In general, higher
      counts of survivors were observed on polyethylene disinfected with different
      concentrations of biocides. S. Bredeney e S. Typhimurium were more resistant than
      S. Enteritidis to PAA, whilst S. Enteritidis presented smaller reduction rates to
      NaOCl. This last biocide was able to reduce Salmonella counts in approximately
      3.0 to 4.0 log cm(-2). When adhered to polyethylene, the serovars S. Typhimurium
      and S. Enteritidis were more resistant to Quat than S. Bredeney in all
      concentrations tested, and the numbers of S. Enteritidis remained almost
      unaltered. On stainless steel disinfected by Quat, S. Bredeney presented higher
      numbers of survivors. 

PMID- 24031584
TI  - Evaluation of different cryoprotective agents in maintenance of viability of
      Helicobacter pylori in stock culture media.
AB  - Four different cryoprotective supplemented stock media were evaluated for
      maintaining better survival and recovery of H. pylori type strain NCTC 11637 at
      two different maintenance temperatures of -20 degrees C and -80 degrees C after
      one month preservation as frozen stocks. The spread plate colony count method was
      used to investigate the recovery rate of H. pylori from equally inoculated
      bacterial suspensions in differently prepared stock cultures. After the
      preservation of H. pylori for one month in different cryoprotectant-supplemented
      stock media, the recovery rates for -20 degrees C obtained for stock cultures
      supplemented with dimethyl sulfoxide (DMSO), polyethylene glycol (PEG), glycerol
      and glycerol+sucrose, as well as controls with and without human serum alone were
      7.13, 6.97, 7.93, 7.99, 6.95 and 0.0 log CFU/ml, respectively. Maintenance of
      bacteria at -80 degrees C gave statistically higher recovery rates compared to
      preservation at -20 degrees C with the values of 8.55, 8.24, 8.59, 8.66, 8.01 and
      0.0 log CFU/ml for these above mentioned stock cultures. The stock cultures
      supplemented with glycerol+sucrose and glycerol showed the highest recovery
      rates, 7.99 and 7.93 for -20 degrees C vs. 8.66 and 8.59 for -80 degrees C
      respectively, which were statistically different from the others. Our study
      revealed that H. pylori type strain NCTC 11637 could be better preserved at -80
      degrees C than -20 degrees C. The best stock media which supported viability or
      culturability of bacteria were brain heart infusion broth (BHI)+glycerol+human
      serum and BHI+glycerol+sucrose+human serum, where the latter yielded the higher
      recovery rate. 

PMID- 24031585
TI  - Detection of Group B Streptococcus in Brazilian pregnant women and antimicrobial
      susceptibility patterns.
AB  - Group B Streptococcus (GBS) is still not routinely screened during pregnancy in
      Brazil, being prophylaxis and empirical treatment based on identification of risk
      groups. This study aimed to investigate GBS prevalence in Brazilian pregnant
      women by culture or polymerase chain reaction (PCR) associated to the enrichment
      culture, and to determine the antimicrobial susceptibility patterns of isolated
      bacteria, so as to support public health policies and empirical prophylaxis.
      After an epidemiological survey, vaginal and anorectal specimens were collected
      from 221 consenting laboring women. Each sample was submitted to enrichment
      culture and sheep blood agar was used to isolate suggestive GBS. Alternatively,
      specific PCR was performed from enrichment cultures. Antimicrobial susceptibility
      patterns were determined for isolated bacteria by agar diffusion method. No risk
      groups were identified. Considering the culture-based methodology, GBS was
      detected in 9.5% of the donors. Twenty five bacterial strains were isolated and
      identified. Through the culture-PCR methodology, GBS was detected in 32.6%
      specimens. Bacterial resistance was not detected against ampicillin, cephazolin,
      vancomycin and ciprofloxacin, whereas 22.7% were resistant to erythromycin and
      50% were resistant to clindamycin. GBS detection may be improved by the
      association of PCR and enrichment culture. Considering that colony selection in
      agar plates may be laboring and technician-dependent, it may not reflect the real
      prevalence of streptococci. As in Brazil prevention strategies to reduce the GBS
      associated diseases have not been adopted, prospective studies are needed to
      anchor public health policies especially considering the regional GBS
      antimicrobial susceptibility patterns. 

PMID- 24031586
TI  - Microbiota associated with chronic osteomyelitis of the jaws.
AB  - Chronic osteomyelitis of maxilla and mandible is rare in industrialized countries
      and its occurrence in developing countries is associated with trauma and surgery,
      and its microbial etiology has not been studied thoroughly. The aim of this
      investigation was to evaluate the microbiota associated with osteomyelitis of
      mandible or maxilla from some Brazilian patients. After clinical and radiographic
      evaluation, samples of bone sequestra, purulent secretion, and biopsies of
      granulomatous tissues from twenty-two patients with chronic osteomyelitis of
      mandible and maxilla were cultivated and submitted for pathogen detection by
      using a PCR method. Each patient harbored a single lesion. Bacterial isolation
      was performed on fastidious anaerobe agar supplemented with hemin, menadione and
      horse blood for anaerobes; and on tryptic soy agar supplemented with yeast
      extract and horse blood for facultative bacteria and aerobes. Plates were
      incubated in anaerobiosis and aerobiosis, at 37(o)C for 14 and 3 days,
      respectively. Bacteria were cultivated from twelve patient samples; and genera
      Actinomyces, Fusobacterium, Parvimonas, and Staphylococcus were the most
      frequent. By PCR, bacterial DNA was detected from sixteen patient samples. The
      results suggest that cases of chronic osteomyelitis of the jaws are usually mixed
      anaerobic infections, reinforcing the concept that osteomyelitis of the jaws are
      mainly related to microorganisms from the oral environment, and periapical and
      periodontal infections may act as predisposing factors. 

PMID- 24031587
TI  - Ethambutol resistance of indigenous Mycobacterium tuberculosis isolated from
      human patients.
AB  - The present study was conducted to find out the ethambutol resistance pattern of
      indigenous isolates of Mycobacterium tuberculosis from Tuberculosis diagnosed
      human patients. A total of 172 specimens were collected from six different
      sources and comprised of 84.9% sputum, 10.5% pus and 4.7% bronchial washings.
      There were 70.9% males and 29.1% females with 84.30% pulmonary and 15.69% extra
      pulmonary tuberculosis. The Mycobacterium tuberculosis isolates collected from
      primary culture were further studied to determine their pattern and level of
      resistance. The inoculums were prepared using 0.5 Mac Farland turbidity
      standards. Five different concentration of ethambutol were used in Lowenstein
      Jensen (LJ) medium i.e. 2ug/ml, 4ug/ml, 6ug/ml, 8ug/ml and 10ug/ml for
      sensitivity testing. Data showed 10 (5.8%) resistant and 162 (94.2%) sensitive
      Mycobacterium tuberculosis out of total 172 clinical isolates. The growth was not
      inhibited at 1(st) (2ug/ml) and 2(nd) (4ug/ml) drug levels, while growth of 50%
      isolates inhibited at 3(rd) level (6ug/ml), 30% inhibited at 4(th) level (8ug/ml)
      and 20% at 5(th) level (10ug/ml). The last three levels are above the therapeutic
      index and not recommended in actual clinical practice. It is thus conceivable to
      explore some other more effective chemotherapeutic agents, modify combinations or
      find more effective procedures to stop morbidity and mortality due to ethambutol
      resistant Mycobacterium tuberculosis. 

PMID- 24031588
TI  - Rosmarinus officinalis essential oil: antiproliferative, antioxidant and
      antibacterial activities.
AB  - The aim of this work was to investigate and compare the antiproliferative,
      antioxidant and antibacterial activities of Rosmarinus officinalis essential oil,
      native to Pakistan. The essential oil content from the leaves of R. officinalis
      was 0.93 g 100g(-1). The GC and GC-MS analysis revealed that the major components
      determined in R. officinalis essential oil were 1,8-cineol (38.5%), camphor
      (17.1%), alpha-pinene (12.3%), limonene (6.23%), camphene (6.00%) and linalool
      (5.70%). The antiproliferative activity was tested against two cancer (MCF-7 and
      LNCaP) and one fibroblast cell line (NIH-3T3) using the MTT assay, while, the
      antioxidant activity was evaluated by the reduction of 2, 2-diphenyl-1-picryl
      hydrazyl (DPPH) and measuring percent inhibition of peroxidation in linoleic acid
      system. The disc diffusion and modified resazurin microtitre-plate assays were
      used to evaluate the inhibition zones (IZ) and minimum inhibitory concentration
      (MIC) of R. officinalis essential oil, respectively. It is concluded from the
      results that Rosmarinus officinalis essential oil exhibited antiproliferative,
      antioxidant and antibacterial activities. 

PMID- 24031589
TI  - Comparison of the worldwide transmissible Pseudomonas aeruginosa with isolates
      from brazilian cystic fibrosis patients.
AB  - Cross-infection with Pseudomonas aeruginosa among cystic fibrosis (CF) patients
      is a rare occurrence. However, the emergence of transmissible strains has been
      reported between unrelated individuals. We analyzed the genetic relationship
      among P. aeruginosa isolates from Brazilian CF patients and transmissible clones
      which are worldwide spread. The data does not indicate the presence of closely
      related variant clones. 

PMID- 24031590
TI  - Quantification of biofilm production on polystyrene by Listeria, Escherichia coli
      and Staphylococcus aureus isolated from a poultry slaughterhouse.
AB  - This study assessed biofilm formation on polystyrene by Staphylococcus aureus,
      Listeria monocytogenes, L. welshimeri and Escherichia coli, isolated from a
      slaughtering plant, grown on tryptic soy broth (TSB) using different glucose
      concentrations. The tested bacteria produced biofilm in at least one of the
      concentrations used, and some of them were strong biofilm producers. 

PMID- 24031591
TI  - In vitro antibacterial activities of ethanol extract of iranian propolis (EEIP)
      against fish pathogenic bacteria (Aeromonas hydrophila, Yersinia ruckeri &
      Streptococcus iniae).
AB  - The "in vitro" antibacterial activity of ethanol extract of propolis (EEIP) from
      Urmia, Iran was investigated against three prevalent species of fish bacterial
      pathogens including: Aeromonas hydrophila LMG 3770, Yersinia ruckeri LMG 3279 and
      Streptococcus iniae LMG 14520. In this study two standard susceptibility testing
      techniques (Micro-broth dilution method and Agar-well diffusion method) were used
      to evaluation of the antibacterial activity of EEIP against the mentioned micro
      organisms. Also the chemical composition of propolis was determined by the method
      of Gas chromatography-mass spectrometry (GC-MS). Twenty-six compounds were
      identified by gas chromatography-mass spectrometry analysis. Results showed
      Chemical composition of EEIP contained significant amounts of flavonoids,
      Sesquiterpenes - mainly Eudesmol and Caryophyllene oxide - aromatic acid, and low
      amounts of aldehydes and triterpens. Furthermore the ethanol extract of propolis
      inhibited the growth of all examined micro-organisms with the highest
      antimicrobial activity against Gram-positive bacteria Streptococcus iniae.
      Ethanol did not influence the antimicrobial effect of EEIP. These antibacterial
      properties would warrant further studies on the clinical applications of propolis
      in aquaculture field. 

PMID- 24031592
TI  - Partial VP2 sequencing of canine parvovirus (CPV) strains circulating in the
      state of Rio de Janeiro, Brazil: detection of the new variant CPV-2c.
AB  - Canine parvovirus (CPV) is the most important enteric virus for dogs and it seems
      to be undergoing continuous evolution, generating new genetic and antigenic
      variants throughout the world. The aim of this study was to analyze the
      distribution of CPV variants from 1995 to 2009 and to investigate the circulation
      of the new variant CPV-2c in Rio de Janeiro, Brazil. In addition, the clinical
      features of CPV infection were also reported. After CPV laboratorial confirmation
      by HA/HI and PCR, thirty-two fecal samples were analyzed by sequencing a 583-bp
      fragment of the VP2 gene. One sample, collected in 2008 was typed as the new type
      CPV-2c. All samples from 1995 to 2003 were identified as "new CPV-2a". From 2004
      to 2006, both "new CPV-2a" and CPV-2b were observed. From 2006 to 2009, most of
      the samples were characterized as CPV-2b. The classical signs of CPV enteritis
      were observed in 16/18 CPV-2a and 5/13 CPV-2b infected puppies. These results
      show that continuous epidemiological surveillance of CPV strain distribution is
      essential for studying the patterns of CPV-2a and 2b spread and for determining
      whether the new variant CPV-2c has become permanently established in Brazilian
      canine population. 

PMID- 24031593
TI  - Isolation and growth characterization of chlorate and/or bromate resistant
      mutants generated by spontaneous and induced foreword mutations at several gene
      loci in aspergillus niger.
AB  - We aimed her mainly to evaluate the contribution of newly employed bromate
      selection system, in obtaining new Aspergillus niger nitrate/nitrite assimilation
      defective mutants, through Ultraviolet treatment (UV), 1, 2, 7, 8-Diepoxyoctane
      (DEO), phenols mixture (Phx)) and spontaneous treatments. The newly employed
      bromate selection system was able to specify only two putative novel mutant types
      designated brn (bromate resistant but chlorate sensitive (RS) strain, which may
      specify nitrite specific transporter) and cbrn mutants (bromate resistant and
      chlorate resistant strain, which may specify nitrate/nitrite bispecific system).
      The most relevant and innovative findings of this research work involve the
      isolation of the RR ( cbrn) mutants (a new type of nitrate assimilation defective
      mutants), that could be useful for studying the bispecific nitrate /nitrite
      transporter system. The majority of obtained bromate resistant mutants (93.3% of
      the total mutants obtained by all treatments) were of the brn type, whereas the
      remaining percentage (6.76%) was given to cbrn strains. The highest percentages
      of brn mutant strains (48% and 58.6% of the total RS strains) were obtained with
      UA after spontaneous and Phx treatment, whereas Trp has generated 29% and 42% of
      RS strains after UV and DEO treatments, respectively. The obtained ratios of cbrn
      mutants were higher (i.e. in the range of 8.4%-11.64% of the total bromate
      mutants) with chemical treatments, especially when U.A or Pro was serving as sole
      N-sources at 25oC rather than 37oC. A 69% mutants' yield of Aspergillus niger
      mutant strains representing nine gene loci ( niaD, cnx-6 loci , nrt and nirA)
      were selected on the bases of chlorate (600 mM) toxicity. All chlorate resistant
      mutants were completely sensitive to bromate (250 mM). The niaD mutants showed
      the highest percentage (73.97%) of chlorate resistant mutants obtained with all
      tested treatments. The UV treatment has generated the highest ratio (86.9%) of
      niaD mutants, whereas, the least (61%) was obtained with Phx treatment. The
      highest percentage of cnx mutants (32%) was obtained with Phx treatment. The DEO
      treatment as compared to other tested treatments was the best to use for
      obtaining the highest ratios of either nrt (13.8%) mutants or nirA (1.9%)
      mutants. 

PMID- 24031594
TI  - Some optimal culture conditions for production of cyclosporin a by Fusarium
      roseum.
AB  - A suitable chemically defined culture medium was selected and some optimal
      conditions for the production of the highly immunosuppressive compound,
      cyclosporin A (Cyc A) are reported. Medium of the following composition was
      favorable for the production of Cyc A by Fusarium roseum: glucose, 30; NaNO3, 2;
      KH2PO4, 1; MgSO4.7H2O, 0.5 and KCL, 0.5 (g/l). Maximum productivity of Cyc A was
      achieved at pH 6.0 when 50 ml of the fermentation medium/250 ml flask, inoculated
      with five fungal agar discs (6 mm, diameter) of 7-days old F. roseum culture
      after incubation at 30 oC at 120 rpm for 7 days. 

PMID- 24031595
TI  - Production of extracellular lipases by Rhizopus oligosporus in a stirred
      fermentor.
AB  - The present investigation deals with the kinetics of submerged extracellular
      lipases fermentation by both wild and mutant strains of Rhizopus oligosporus
      var.microsporus in a laboratory scale stirred fermentor. Other parameters studied
      were inoculum size, pH, agitation and rate of aeration. It was found that the
      growth and lipases production was increased gradually and reached its maximum
      9.07+/- 0.42(a) U mL(-1) (W) and 42.49 +/- 3.91(a) U mL(-1) (M) after 30h of
      fermentation for both wild and mutant strain. There is overall increase of 109%
      (W) and 124% (M) in the production of extracellular lipases as compared to shake
      flask. Another significant finding of the present study is that the fermentation
      period is reduced to 30 h in case of wild and 23 h in case of mutant from 48 h in
      shake flask studies. The specific productivity of mutant strain (qp = 377.3 U/g
      cells/h) was several folds higher than wild strain. The specific production rate
      and growth coefficient revealed the hyperproducibility of extracellular lipases
      using mutant IIB-63NTG-7. 

PMID- 24031596
TI  - Improvement of penicillin G acylase expression in Escherichia coli through UV
      induced mutations.
AB  - We used ultraviolet (UV) radiation to induce mutation in three locally isolated
      strains of Escherichia coli. Different dilutions of bacterial cultures were
      exposed to UV lamp of 254 nm wavelength for different time intervals at varied
      distances ranging from 5 to 210 sec and 5 to 100 cm. Viable colonies were
      screened for mutants with an increased production of penicillin G acylase (PGA)
      and a reduced production of beta-lactamase, which are the desired properties of
      PGA producing industrial strains. A survival curve was made to get optimum
      exposure time and distance. The survival percentage for each exposure period was
      calculated and 1-5% survival was found useful for obtaining mutants with desired
      change. Screening for PGA and beta-lactamase constitutive and/or deficient
      mutants was made by Serratia marcescens overlay test. A total of 100 survivors
      were selected of which 49% expressed PGA activity higher than the parent strain.
      Frequency of beta-lactamase constitutive and deficient mutants was 48 and 52%,
      respectively. The best hyper-producing mutant (BDCS-N-M74), with almost
      negligible expression of beta-lactamase, exhibited three-fold (22.5 mg 6-APA h(
      1) mg(-1) wet cells) increase in PGA activity compared with that in the parent
      strain (6.7 mg 6-APA h(-1) mg(-1) wet cells). The results indicated the
      successful induction of UV mediated mutation in E. coli for PGA hyper-producing
      mutants lacking beta-lactamase activity. 

PMID- 24031597
TI  - Application of representational difference analysis to identify genomic
      differences between Bradyrhizobium elkanii and B. Japonicum species.
AB  - Bradyrhizobium elkanii is successfully used in the formulation of commercial
      inoculants and, together with B. japonicum, it fully supplies the plant nitrogen
      demands. Despite the similarity between B. japonicum and B. elkanii species,
      several works demonstrated genetic and physiological differences between them. In
      this work Representational Difference Analysis (RDA) was used for genomic
      comparison between B. elkanii SEMIA 587, a crop inoculant strain, and B.
      japonicum USDA 110, a reference strain. Two hundred sequences were obtained. From
      these, 46 sequences belonged exclusively to the genome of B. elkanii strain, and
      154 showed similarity to sequences from B. japonicum genome. From the 46
      sequences with no similarity to sequences from B. japonicum, 39 showed no
      similarity to sequences in public databases and seven showed similarity to
      sequences of genes coding for known proteins. These seven sequences were divided
      in three groups: similar to sequences from other Bradyrhizobium strains, similar
      to sequences from other nitrogen-fixing bacteria, and similar to sequences from
      non nitrogen-fixing bacteria. These new sequences could be used as DNA markers in
      order to investigate the rates of genetic material gain and loss in natural
      Bradyrhizobium strains. 

PMID- 24031598
TI  - Microbial deterioration of vacuum-packaged chilled beef cuts and techniques for
      microbiota detection and characterization: a review.
AB  - Gas production from microbial deterioration in vacuum-packs of chilled meat leads
      to pack distension, which is commonly referred as blown pack. This phenomenon is
      attributed to some psychrophilic and psychrotrophic Clostridium species, as well
      as Enterobacteria. The ability of these microorganisms to grow at refrigeration
      temperatures makes the control by the meat industry a challenge. This type of
      deterioration has been reported in many countries including some plants in the
      Midwestern and Southeastern regions of Brazil. In addition to causing economic
      losses, spoilage negatively impacts the commercial product brand, thereby
      impairing the meat industry. In the case of strict anaerobes species they are
      difficult to grow and isolate using culture methods in conventional microbiology
      laboratories. Furthermore, conventional culture methods are sometimes not capable
      of distinguishing species or genera. DNA-based molecular methods are alternative
      strategies for detecting viable and non-cultivable microorganisms and strict
      anaerobic microorganisms that are difficult to cultivate. Here, we review the
      microorganisms and mechanisms involved in the deterioration of vacuum-packaged
      chilled meat and address the use of molecular methods for detecting specific
      strict anaerobic microorganisms and microbial communities in meat samples. 

PMID- 24031599
TI  - Beauveria bassiana: Quercetinase production and genetic diversity.
AB  - Beauveria bassiana genetic diversity and ability to synthesize quercetin 2,3
      dioxygenase (quercetinase) were analyzed. B. bassiana isolates, obtained from
      Brazilian soil samples, produced quercetinase after induction using 0.5 g/L
      quercetin. B. bassiana ATCC 7159 (29.6 nmol/mL/min) and isolate IP 11 (27.5
      nmol/ml/min) showed the best performances and IP 3a (9.5 nmol/mL/min) presented
      the lowest level of quercetinase activity in the culture supernatant. A high
      level of polymorphism was detected by random amplified polymorphic DNA (RAPD)
      analysis. The use of internal-transcribed-spacer ribosomal region restriction
      fragment length polymorphism (ITS-RFLP) did not reveal characteristic markers to
      differentiate isolates. However, the ITS1-5.8S-ITS2 region sequence analysis
      provided more information on polymorphism among the isolates, allowing them to be
      clustered by relative similarity into three large groups. Correlation was tested
      according to the Person's correlation. Data of our studies showed, that lower
      associations among groups, level of quercetinase production, or geographical
      origin could be observed. This study presents the production of a novel
      biocatalyst by B. bassiana and suggests the possible industrial application of
      this fungal species in large-scale biotechnological manufacture of quercetinase. 

PMID- 24031600
TI  - Characterization of a novel lipase from Bacillus sp. isolated from tannery
      wastes.
AB  - Kinetics of a lipase isolated from Bacillus sp. was studied. The enzyme showed
      maximum activity at pH 9 and temperature 60 degrees C. The Michaelis constant (KM
      0.31 mM) obtained from three different plots i.e., Lineweaver-Burk, Hanes-Wolf
      and Hofstee, was found to be lower than already reported lipases that confirmed
      higher affinity of the enzyme for its substrate p-NPL (p-nitrophenyl laurate).
      Vmax of the enzyme was found to be 7.6 uM/mL/min. Energy of activation calculated
      from Arrhenius plot was found to be 20.607 kJmol(-1). Activation enthalpy
      (DeltaH*) had negative trend and the value for the hydrolysis of p-NPL by the
      enzyme at optimum temperature was -2.748 kJmol(-1). Activation entropy (DeltaS*)
      and free energy of activation (DeltaG*) of the enzyme were found to be 1.468
      Jmol(-1)K(-1) and -3.237 kJmol(-1), respectively at optimum temperature. Low
      value of Q10 (0.04788) shows high catalytic activity of the enzyme. Mn(2+),
      Fe(2+) and Mg(2+) enhanced the lipase activity whereas Cu(2+), Na(+) and Co(2+)
      inhibited the enzyme activity. However, the enzyme activity was not affected
      significantly by K(+) ions. EDTA and SDS also significantly inhibited the lipase
      activity. Activity of the enzyme was increased in n-hexane while decreased with
      increase in concentration of acetone, chloroform, ethanol and isopropanol. 

PMID- 24031601
TI  - Quantitative changes in the biochemical composition of lignocellulosic residues
      during the vegetative growth of Lentinula edodes.
AB  - The chemical changes in barley-straw (BS), wheat-straw (WS) and vineyard-pruning
      (VP) substrates were determined during colonization of Lentinula edodes mycelia
      (during primordium development) in solid state fermentation. Primordia appeared
      39-50 days after inoculation. VP appeared to promote early sporophore initiation.
      The concentration of hemicellulose in BS and VP decreased gradually from 25.5% to
      15.6% and from 15.8% to 12.3%, respectively. However in WS, hemicellulose
      decreased from 27.2% to 9.5%. Lignin broke down continuously in BS and WS, with
      31.8% and 34.4% degradation, respectively; higher than that of cellulose. During
      the pinning stage, the C:N ratio decreased in VP and BS, but not in WS. On all
      substrates the phenols decreased notably throughout the first week of mycelial
      growth. The time elapsed (days) to pinning was positively correlated with
      cellulose content (r=0.89), total sugar (r=0.85) and inversely correlated to
      lignin (r=-1.00) and phenol content (r=-0.55). 

PMID- 24031602
TI  - Succession and growth strategy of a spring microbial community from kezhou sinter
      in china.
AB  - The succession and growth strategy of a spring microbial community under
      earthquake action were investigated. The majority of pre-earthquake isolates
      belonged to the Gammaproteobacteria, including two numerically dominant
      Stenotrophomonas sp. RB25 and Acinetobacter sp. RB11 (r-strategists). The
      predominant post-earthquake isolates were Alphaproteobacteria, with Rhizobium sp.
      RA42 (K-strategists) being dominant among these organisms. 

PMID- 24031603
TI  - Evaluating most probable number method to count and isolate viable methylotrophs.
AB  - Nine different receptacles were tested with the MPN method to determine which
      receptacle was most reliable and economical for MPN counts. Results showed that
      96 well PCR plate were the best vessels for this type of analysis and facilitated
      the isolation of viable Methylotrophs. 

PMID- 24031604
TI  - Culturable fungal diversity of shrimp Litopenaeus vannamei boone from breeding
      farms in brazil.
AB  - Litopenaeus vannamei, which is the most common shrimp species cultivated in the
      northeast of Brazil, is very susceptible to microbial diseases, and this
      consequently affects productivity. There are reports of bacteria, viruses and
      protozoa in these shrimp, but not fungi. This study aims to isolate and identify
      fungi present in shrimp Litopenaeus vannamei, and in their nursery waters, at two
      breeding farms in Brazil. The pathogenic potential of the isolates was assessed
      through the qualitative detection of proteases and aflatoxin B production. The
      146 isolated fungi comprised 46 species. Aspergillus, Penicillium and Furarium
      were the three most relevant genera and Aspergillus flavus was the predominant
      species with a total of 33 isolates. Most of the isolated species are known as
      potentially pathogenic to humans and other animals. Eighteen isolates of A.
      flavus and two of A. parasiticus were able to produce aflatoxin B and 33 out of
      the 46 species produced protease, indicating that these fungi may also become
      pathogenic to shrimp and their consumers. 

PMID- 24031605
TI  - Seasonality and host preference of arbuscular mycorrhizal fungi of five plant
      species in the inner mongolia steppe, china.
AB  - The seasonal change and host preference of arbuscular mycorrhizal (AM)
      colonization and community composition of five common plant species Agropyron
      cristatum, Anemarrhena asphodeloides, Cleistogenes squarrosa, Leymus chinensis,
      and Stipa grandis in the Inner Mongolia steppe were investigated. The AM root
      length colonization rates were different among the five plant species and were
      generally high in early (May and June) and late (September) growth seasons and
      low in August. A total of 18 AM fungal species representing five genera were
      isolated from rhizosphere soils of the five plant species, and most AM fungi had
      not host specificity, except that Acaulospora sp., Glomus constrictum, G.
      diaphanum and Glomus sp. showed a certain degree of host preference. Glomus
      albidum, G. etunicatum and G. geosporum were the dominant species and showed
      various sporulation patterns in the five plants during the growth seasons. The AM
      fungal spore densities and species richness increased from May to September and
      decreased in October and were different in the same month in the five plants.
      Multivariate analyses revealed that season and host significantly co-affected the
      AM fungal spore density, species richness, and Shannon-Wiener diversity index,
      and the season had higher influence than the host. 

PMID- 24031606
TI  - Evaluation of copper resistant bacteria from vineyard soils and mining waste for
      copper biosorption.
AB  - Vineyard soils are frequently polluted with high concentrations of copper due
      application of copper sulfate in order to control fungal diseases. Bioremediation
      is an efficient process for the treatment of contaminated sites. Efficient copper
      sorption bacteria can be used for bioremoval of copper from contaminated sites.
      In this study, a total of 106 copper resistant bacteria were examined for
      resistance to copper toxicity and biosorption of copper. Eighty isolates (45 from
      vineyard Mollisol, 35 from Inceptisol) were obtained from EMBRAPA (Empresa
      Brasileira de Pesquisa Agropecuaria) experimental station, Bento Goncalves, RS,
      Brazil (29 degrees 09'53.92"S and 51 degrees 31'39.40"W) and 26 were obtained
      from copper mining waste from Cacapava do Sul, RS, Brazil (30 degrees 29'43.48"S
      and 53'32'37.87W). Based on resistance to copper toxicity and biosorption, 15
      isolates were identified by 16S rRNA gene sequencing. Maximal copper resistance
      and biosorption at high copper concentration were observed with isolate N2 which
      removed 80 mg L(-1) in 24 h. Contrarily isolate N11 (Bacillus pumilus) displayed
      the highest specific copper biosorption (121.82 mg/L/OD unit in 24 h). GenBank
      MEGABLAST analysis revealed that isolate N2 is 99% similar to Staphylococcus
      pasteuri. Results indicate that several of our isolates have potential use for
      bioremediation treatment of vineyards soils and mining waste contaminated with
      high copper concentration. 

PMID- 24031607
TI  - Xylanase and cellulase activities during anaerobic decomposition of three aquatic
      macrophytes.
AB  - Enzymatic activity during decomposition is extremely important to hydrolyze
      molecules that are assimilated by microorganisms. During aquatic macrophytes
      decomposition, enzymes act mainly in the breakdown of lignocellulolytic matrix
      fibers (i.e. cellulose, hemicellulose and lignin) that encompass the refractory
      fraction from organic matter. Considering the importance of enzymatic activities
      role in decomposition processes, this study aimed to describe the temporal
      changes of xylanase and cellulose activities during anaerobic decomposition of
      Ricciocarpus natans (freely-floating), Oxycaryum cubense (emergent) and Cabomba
      furcata (submersed). The aquatic macrophytes were collected in Oleo Lagoon, Luiz
      Antonio, Sao Paulo, Brazil and bioassays were accomplished.  Decomposition
      chambers from each species (n = 10) were set up with dried macrophyte fragments
      and filtered Oleo Lagoon water. The chambers were incubated at 22.5 degrees C, in
      the dark and under anaerobic conditions. Enzymatic activities and remaining
      organic matter were measured periodically during 90 days. The temporal variation
      of enzymes showed that C. furcata presented the highest decay and the highest
      maximum enzyme production. Xylanase production was higher than cellulase
      production for the decomposition of the three aquatic macrophytes species. 

PMID- 24031608
TI  - Chromobacterium sp. From the tropics: detection and diversity of phytase
      activity.
AB  - Phytases are a group of enzymes that catalyze phytic acid hydrolysis with release
      of phosphorus (P). The ability of Chromobacterium sp. to produce phytase was
      detected in 115 out of 118 candidate bacteria isolated from different Brazilian
      biomas. This is the first report revealing the genus Chromobacterium as phytase
      producer. 

PMID- 24031609
TI  - Zygomycetes From Herbivore Dung in the Ecological Reserve of Dois IrmAOs,
      Northeast Brazil.
AB  - Thirty-eight taxa of Zygomycetes distributed in 15 genera were recorded from
      tapir (Tapirus terrestris), camel (Camelus bactrianus), horse (Equus caballus),
      deer (Cervus elaphus), agouti (Dasyprocta aguti), donkey (Equus asinus), llama
      (Llama glama) and waterbuck (Kobus ellipsiprymnus) dung collected at the Reserva
      Ecologica de Dois Irmaos located in Recife, State of Pernambuco, Northeast
      Brazil. The samples were collected on a monthly basis from June 2005 to May 2006,
      taken to the laboratory and incubated in moist chambers. Higher number of taxa
      was observed in the excrements of tapir, followed by deer and donkey. The highest
      number of species was detected for Mucor, followed by Pilobolus. Statistical
      analyses showed significant differences in richness of Zygomycetes taxa between
      the herbivore dung types. Differences of species composition, however, were weak.
      Seasonality influenced the Zygomycetes species composition but not its richness.
      Variations in taxa composition between ruminants and non-ruminants dung were non
      significant. 

PMID- 24031610
TI  - Characterization and comparison of serratia marcescens isolated from edible
      cactus and from silkworm for virulence potential and chitosan susceptibility.
AB  - Representative strains of Serratia marcescens from an edible cactus plant and
      silkworms were characterized and a comparison based on their cellular fatty acid
      composition, 16S rRNA and groE gene sequence analysis as well as silkworm
      virulence and chitosan susceptibility was carried out. Results from this study
      indicate that there are no significant differences between the phenotypic and
      molecular characterization, virulence and chitosan susceptibility of the S.
      marcescens strains from the cactus plant and silkworms. Silkworms inoculated with
      S. marcescens from either plant or silkworm resulted in nearly 100% mortality.
      Chitosan solution exhibited strong antibacterial activity against S. marcescens.
      This activity increased with the increase of chitosan concentration and
      incubation time regardless of the strain source. Also, the results indicate that
      the plant associated S. marcescens maybe plays a possible role in the
      contamination of humans and animals, in particular silkworms, while chitosan
      showed a potential to control the contamination caused by S. marcescens. 

PMID- 24031611
TI  - The nematicidal effect of some bacterial biofertilizers on Meloidogyne incognita
      in sandy soil.
AB  - In a greenhouse experiment, the nematicidal effect of some bacterial
      biofertilizers including the nitrogen fixing bacteria (NFB) Paenibacillus
      polymyxa (four strains), the phosphate solubilizing bacteria (PSB) Bacillus
      megaterium (three strains) and the potassium solubilizing bacteria (KSB) B.
      circulans (three strains) were evaluated individually on tomato plants infested
      with the root-knot nematode Meloidogyne incognita in potted sandy soil. Comparing
      with the uninoculated nematode-infested control, the inoculation with P. polymyxa
      NFB7, B. megaterium PSB2 and B. circulans KSB2, increased the counts of total
      bacteria and total bacterial spores in plants potted soil from 1.2 to 2.6 folds
      estimated 60 days post-inoculation. Consequently, the inoculation with P.
      polymyxa NFB7 increased significantly the shoot length (cm), number of leaves /
      plant, shoot dry weight (g) / plant and root dry weight (g) / plant by 32.6 %,
      30.8 %, 70.3 % and 14.2 %, respectively. Generally, the majority treatments
      significantly reduced the nematode multiplication which was more obvious after 60
      days of inoculation. Among the applied strains, P. polymyxa NFB7, B. megaterium
      PSB2 and B. circulans KSB2 inoculations resulted in the highest reduction in
      nematode population comparing with the uninoculated nematode-infested control.
      They recorded the highest reduction in numbers of hatched juveniles/root by 95.8
      %, females/root by 63.75 % and juveniles/1kg soil by 57.8 %. These results
      indicated that these bacterial biofertilizers are promising double purpose
      microorganisms for mobilizing of soil nutrients (nitrogen, phosphate and
      potassium) and for the biological control of M. incognita. 

PMID- 24031612
TI  - Structural Interaction Between GFP-Labeled Diazotrophic Endophytic Bacterium
      Herbaspirillum seropedicae RAM10 and Pineapple Plantlets 'VitoRia'.
AB  - The events involved in the structural interaction between the diazotrophic
      endophytic bacterium Herbaspirillum seropedicae, strain RAM10, labeled with green
      fluorescent protein, and pineapple plantlets 'Vitoria' were evaluated by means of
      bright-field and fluorescence microscopy, combined with scanning electron
      microscopy for 28 days after inoculation. After 6 hours of inoculation, H.
      seropedicae was already adhered to the roots, colonizing mainly root hair surface
      and bases, followed by epidermal cell wall junctions. Bacteria adherence in the
      initial periods occurred mainly in the form of solitary cells and small
      aggregates with pleomorphic cells. Bacteria infection of root tissue occurred
      through the cavities caused by the disruption of epidermal cells during the
      emergence of lateral roots and the endophytic establishment by the colonization
      of intercellular spaces of the cortical parenchyma. Moreover, within 1 day after
      inoculation the bacteria were colonizing the shoots. In this region, the
      preferred sites of epiphytic colonization were epidermal cell wall junctions,
      peltate scutiform trichomes and non-glandular trichomes. Subsequently, the
      bacteria occupied the outer periclinal walls of epidermal cells and stomata. The
      penetration into the shoot occurred passively through stoma aperture followed by
      the endophytic establishment on the substomatal chambers and spread to the
      intercellular spaces of spongy chlorenchyma. After 21 days of inoculation,
      bacterial biofilm were seen at the root hair base and on epidermal cell wall
      surface of root and leaf, also confirming the epiphytic nature of H. seropedicae.

PMID- 24031613
TI  - The occurrence of Aeromonas in drinking water, tap water and the porsuk river.
AB  - The occurrence of Aeromonas spp. in the Porsuk River, public drinking water and
      tap water in the City of Eskisehir (Turkey) was monitored. Fresh water samples
      were collected from several sampling sites during a period of one year. Total 102
      typical colonies of Aeromonas spp. were submitted to biochemical tests for
      species differentiation and of 60 isolates were confirmed by biochemical tests.
      Further identifications of isolates were carried out first with the VITEK system
      (BioMe~rieux) and then selected isolates from different phenotypes (VITEK types)
      were identified using the DuPont Qualicon RiboPrinter(r) system. Aeromonas spp.
      was detected only in the samples from the Porsuk River. According to the results
      obtained with the VITEK system, our isolates were 13% Aeromonas hydrophila, 37%
      Aeromonas caviae, 35% Pseudomonas putida, and 15% Pseudomonas acidovorans. In
      addition Pseudomonas sp., Pseudomonas maltophila, Aeromonas salmonicida,
      Aeromonas hydrophila, and Aeromonas media species were determined using the
      RiboPrinter(r) system. The samples taken from the Porsuk River were found to
      contain very diverse Aeromonas populations that can pose a risk for the residents
      of the city. On the other hand, drinking water and tap water of the City are free
      from Aeromonas pathogens and seem to be reliable water sources for the community.

PMID- 24031614
TI  - Molecular identification of methanogenic archaea from surti buffaloes (bubalus
      bubalis), reveals more hydrogenotrophic methanogens phylotypes.
AB  - Methane emissions from ruminant livestock are considered to be one of the more
      potent forms of greenhouses gases contributing to global warming. Many strategies
      to reduce emissions are targeting the methanogens that inhabit the rumen, but
      such an approach can only be successful if it targets all the major groups of
      ruminant methanogens. Therefore, a thorough knowledge of the diversity of these
      microbes in breeds of buffaloes, as well as in response to geographical location
      and different diets, is required. Therefore, molecular diversity of rumen
      methanogens in Surti buffaloes was investigated using 16S rRNA gene libraries
      prepared from pooled rumen contents from three Surti buffaloes. A total of 171
      clones were identified revealing 23 different sequences (phylotypes). Of these 23
      sequences, twelve sequences (12 OTUs, 83 clones) and 10 sequences (10 OTUs, 83
      clones) were similar to methanogens belonging to the orders Methanomicrobiales
      and Methanobacteriales, and the remaining 1 phylotype (5 clones) were similar to
      Methanosarcina barkeri. These unique sequences clustered within a distinct and
      strongly supported phylogenetic group. Further studies and effective strategies
      can be made to inhibit the growth of Methanomicrobiales and Methanobacteriales
      phylotypes to reduce the methane emission from rumen and thus help in preventing
      global warming. 

PMID- 24031615
TI  - Characterization of cry2-type genes of bacillus thuringiensis strains from
      soilisolated of sichuan basin, china.
AB  - Sichuan basin, situated in the west of China, is the fourth biggest basin in
      China. In order to describe a systematic study of the cry2-type genes resources
      from Bacillus thuringiensis strains of Sichuan basin, a total of 791 Bacillus
      thuringiensis strains have been screened from 2650 soil samples in different
      ecological regions. The method of PCR-restriction fragment length polymorphism
      (PCR-RFLP) was used to identify the type of cry2 genes. The results showed that
      322 Bacillus thuringiensis strains harbored cry2-type genes and four different
      RFLP patterns were found. The combination of cry2Aa/cry2Ab genes was the most
      frequent (90.4%), followed by cry2Aa (6.8%) and cry2Ab alone (2.5%), and only one
      novel type of cry2 gene was cloned from one isolate (JF19-2). The full-length of
      this novel gene was obtained by the method of thermal asymmetric interlaced PCR
      (Tail-PCR), which was designated as cry2Ag1 (GenBank No. ACH91610) by the Bt
      Pesticide Crystal Protein Nomenclature Committee. In addition, the result of
      scanning electron microscopic (SEM) observation showed that these strains had
      erose, spherical, bipyramidal, and square crystal. And the results of sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that
      these strains harbored about one to three major proteins. These strains exhibited
      a wide range of insecticidal spectrum toxic to Aedes aegypti (Diptera) and Pieris
      rapae Linnaeus, 1758 (Lepidoptera). Particularly, JF19-2 contained cry2Ag gene
      had the highest insecticidal activity. All these researches mentioned above
      revealed the diversity and particularity of cry2-type gene resources from
      Bacillus thuringiensis strains in Sichuan basin. 

PMID- 24031616
TI  - Comparative Analysis of two Component Signal Transduction Systems of the
      Lactobacillus Acidophilus Group.
AB  - The Lactobacillus acidophilus group is a phylogenetically distinct group of
      closely related lactobacilli. Members of this group are considered to have
      probiotic properties and occupy different environmental niches. Bacteria
      generally sense and respond to environmental changes through two component
      systems (TCSs) which consist of a histidine protein kinase (HPK) and its cognate
      response regulator (RR). With the use of in silico techniques, the five
      completely sequenced L. acidophilus group genomes were scanned in order to
      predict TCSs. Five to nine putative TCSs encoding genes were detected in
      individual genomes of the L. acidophilus group. The L. acidophilus group HPKs and
      RRs were classified into subfamilies using the Grebe and Stock classification
      method. Putative TCSs were analyzed with respect to conserved domains to predict
      biological functions. Putative biological functions were predicted for the L.
      acidophilus group HPKs and RRs by comparing them with those of other
      microorganisms. Some of TCSs were putatively involved in a wide variety of
      functions which are related with probiotic ability, including tolerance to acid
      and bile, production of antimicrobial peptides, resistibility to the glycopeptide
      antibiotic vancomycin, and oxidative condition. 

PMID- 24031617
TI  - Characterization of Lactobacillus from Algerian Goat'S Milk Based on Phenotypic,
      16S rDNA Sequencing and their Technological Properties.
AB  - Nineteen strains of Lactobacillus isolated from goat's milk from farms in north
      west of Algeria were characterized. Isolates were identified by phenotypic,
      physiological and genotypic methods and some of their important technological
      properties were studied. Phenotypic characterization was carried out by studying
      physiological, morphological characteristics and carbohydrate fermentation
      patterns using API 50 CHL system. Isolates were also characterized by partial 16S
      rDNA sequencing. Results obtained with phenotypic methods were correlated with
      the genotypic characterization and 13 isolates were identified as L. plantarum,
      two isolates as L. rhamnosus and one isolate as L. fermentum. Three isolates
      identified as L. plantarum by phenotypic characterization were found to be L.
      pentosus by the genotypic method. A large diversity in technological properties
      (acid production in skim milk, exopolysaccharide production, aminopeptidase
      activity, antibacterial activity and antibiotic susceptibility) was observed.
      Based on these results, two strains of L. plantarum (LbMS16 and LbMS21) and one
      strain of L. rhamnosus (LbMF25) have been tentatively selected for use as starter
      cultures in the manufacture of artisanal fermented dairy products in Algeria. 

PMID- 24031618
TI  - Patulin accumulation in apples during storage by penicillium expansum and
      penicillium griseofulvum strains.
AB  - A part of apples destined to juice production is generally of poor quality.
      Apples from cold storage or recently harvest (ground harvested or low quality
      apples) are stored under ambient conditions until they are processed. Since
      Penicillium expansum and P. griseofulvum are the principal fungal species
      isolated from stored apples in Brazil, the objective of this study was to
      investigate the ability of these strains to produce patulin in apples and report
      the consequences of this type of storage in loss of quality. The toxin was
      quantified using thin layer chromatography and charge-coupled device camera (TLC
      CCD). The rate and quantities that P. expansum and P. griseofulvum can grow and
      produce patulin are highly dependent on the fungal strain and time. Lesion
      diameter resulted to be independent of the strain considered. The maximum period
      of time which apples were kept at cold storage (4  degrees C) without patulin
      accumulation was 27 days. When these apples were kept at 25  degrees C during 3
      days, both factors lesion diameter and patulin production increased
      significantly. These results confirm that time in which apples are taken out from
      cold storage room before juice production is critical in order to prevent patulin
      accumulation. 

PMID- 24031619
TI  - Comparative analysis of cultural isolation and PCR based assay for detection of
      campylobacter jejuni in food and faecal samples.
AB  - In the present study, the efficacy of polymerase chain reaction (PCR) based on
      mapA gene of C. jejuni was tested for detection of Campylobacter jejuni in
      naturally infected as well as spiked faecal and food samples of human and animal
      origin. Simultaneously, all the samples were subjected to the cultural isolation
      of organism and biochemical characterization. The positive samples resulted in
      the amplification of a DNA fragment of size ~589 bp in PCR assay whereas the
      absence of such amplicon in DNA extracted from E. coli, Listeria, Salmonella and
      Staphylococcus confirmed the specificity of the primers. Of randomly collected
      143 faecal samples comprising human diarrheic stools (43), cattle diarrheic
      faeces (48) and poultry faecal swabs (52) only 4, 3 and 8, respectively, could be
      detected by isolation whereas 6, 3 and 10, respectively, were found positive by
      PCR. However, among food samples viz. beef (30), milk (35), cheese (30), only one
      beef sample was detected both by culture as well as PCR. Additionally, PCR was
      found to be more sensitive for C. jejuni detection in spiked faecal and food
      samples (96.1% each) as relative to culture isolation which could detect the
      organism in 86.7% and 80% samples, respectively. The results depicted the
      superior efficacy of PCR for rapid screening of samples owing to its high
      sensitivity, specificity and automation potential. 

PMID- 24031620
TI  - Antimicrobial activity of essential oils against vancomycin-resistant enterococci
      (vre) and Escherichia coli o157:h7 in feta soft cheese and minced beef meat.
AB  - Eleven essential oils (EOs) were evaluated for their antibacterial properties,
      against Vancomycin-Resistant Enterococci (VRE) and E. coli O157:H7. EOs were
      introduced into Brain Heart Infusion agar (BHI) (15ml) at a concentration of 0.25
      to 2% (vol/vol) to determine the minimum inhibitory concentration (MIC) and
      minimum bactericidal concentration (MBC) for each pathogen evaluated. Results
      showed that the most active essential oils against bacteria tested were thyme
      oil, with MIC90 and MBC90 for the VRA strains of 0.25% and 0.5%, respectively.
      Eucalyptus, juniper and clove oils were the least potent agent, with MIC90 and
      MBC90 of 2%. Furthermore, the inhibitory effect of these EO were evaluated
      against VRE and E. coli O157:H7, experimentally inoculated (10(3) cfu/g) in Feta
      soft cheese and minced beef meat, which was mixed with different concentrations
      (0.1%, 0.5% and 1%) of the EO and stored at 7  degrees C for 14 days. Out of
      eucalyptus, juniper, mint, rosemary, sage, clove and thyme oils tested against
      target bacteria sage and thyme showed the best results. Clove and mint did not
      show any effect on VRE and E. coli O157:H7 in both kinds of studied foods. The
      addition of thyme oil at concentrations of 0.5 and 1% caused best significant
      reduction in the growth rate of VRE and E. coli O157:H7 in cheese and meat at 7
      (o)C. It is concluded that selected plant EOs can act as potent inhibitors of
      both microorganisms in a food product. The results revealed the potential of
      thyme oil as a natural preservative in feta soft cheese and minced beef meat
      against VRE and E. coli O157:H7 contamination. 

PMID- 24031621
TI  - Antioxidant Activity of Agaricus brasiliensis Basidiocarps on Different
      Maturation Phases.
AB  - Different maturation phases of basidiocarp could affect the bioactivity and
      concentration of some active substances. A. brasiliensis Wasser et al. (A. blazei
      Murrill) has shown antitumor activity that could be related to the antioxidant
      activity. However there is no information of the best basidiocarp maturation
      phase for extracting antioxidant substances in order to determine the moment of
      harvesting in mushroom cultivation. The objective of this work was to evaluate
      the antioxidant activity of A. brasiliensis strains on different basidiocarp
      maturation phases. The best condition for extraction of A. brasiliensis
      antioxidants is with methanol as solvent at 60  degrees C for 60 min. Strains
      with closed basidiocarp have higher antioxidant activity than with opened
      basidiocarp. Antioxidant activity varies in each strain. It was concluded that A.
      brasiliensis is a natural source of antioxidant compounds. Also there is higher
      antioxidant activity in closed than opened caps and consequently higher
      functional activity. It reinforces the synergic action among different A.
      brasiliensis compounds as a functional food and the importance of further
      investigation for isolation and characterization of antioxidant substances of A.
      brasiliensis. It also determines the best harvest period in order to obtain the
      highest antioxidant activity from basidiocarp. 

PMID- 24031622
TI  - Growth of byssochlamys nivea in pineapple juice under the effect of water
      activity and ascospore age.
AB  - The study of thermal resistant mould, including Byssochlamys nivea, is of extreme
      importance since it has been associated with fruit and fruit products. The aim of
      this work is to analyze the influence of water activity (aw) and ascospore age
      (I) on the growth of Byssochlamys nivea in pineapple juice. Mold growth was
      carried out under different conditions of water activity (aw) (0.99, 0.96, 0.95,
      0.93, 0.90) and ascospore age (I) (30, 51, 60, 69, 90 days). Growth parameters as
      length of adaptation phase (lambda), maximum specific growth rate (umax) and
      maximum diameter reached by the colony (A) were obtained through the fit of the
      Modified Gompertz model to experimental data (measuring radial colony diameter).
      Statistica 6.0 was used for statistical analyses (significance level alpha =
      0.05). The results obtained clearly showed that water activity is statistically
      significant and that it influences all growth parameters, while ascospore age
      does not have any statistically significant influence on growth parameters. Also,
      these data showed that by increasing aw from 0.90 to 0.99, the lambda value
      substantially decreased, while umax and A values rose. The data contributed for
      the understanding of the behavior of B. nivea in pineapple juice. Therefore, it
      provided mathematical models that can well predict growth parameters, also
      helping on microbiological control and products' shelf life determination. 

PMID- 24031623
TI  - Detection of quinolone-resistance mutations in salmonella spp. Strains of
      epidemic and poultry origin.
AB  - Mutations into codons Aspartate-87 (62%) and Serine-83 (38%) in QRDR of gyrA were
      identified in 105 Salmonella strains resistant to nalidixic acid (94 epidemic and
      11 of poultry origin). The results show a high incidence of mutations associated
      to quinolone resistance but suggest association with others mechanisms of
      resistance. 

PMID- 24031624
TI  - The potential inhibitory effect of cuminum cyminum, ziziphora clinopodioides and
      nigella sativa essential oils on the growth of Aspergillus fumigatus and
      Aspergillus.
AB  - The goals of this study were to evaluate the effectiveness of Cuminum cyminum,
      Ziziphora clinopodioides and Nigella sativa essential oils to inhibit the growth
      of Aspergillus fumigatus and A. flavus and to evoke ultrastructural changes. The
      fungi were cultured into RPMI 1640 media in the presence of oils at
      concentrations of 8, 6, 5, 4, 3, 2, 1.5, 1.25, 1, 0.75 and 0.5 mg/ml in broth
      microdilution and 2, 1.5, 1 and 0.5 mg/ml in broth macrodilution methods with
      shaking for 48 h at 28(o)C. Conidial and mycelial samples exposed to 0.25, 0.5,
      1, 1.5 and 2 mg essential oils/ml for 5 days in 2% yeast extract granulated plus
      15% Saccharose media were processed for transmission electron microscopy (TEM).
      Based on broth dilution methods, C. cyminum and to a lesser extent Z.
      clinopodioides oils exhibited the strongest activity against A. fumigatus and A.
      flavus with MIC90 ranging from 0.25 to 1.5 mg/ml, while the oil from N. sativa
      exhibited relatively moderate activity against two above fungi with MIC90 ranging
      from 1.5 to 2 mg/ml. The main changes observed by TEM were in the cell wall,
      plasma membrane and membranous organelles; in particular, in the nuclei and
      mitochondria. These modifications in fungal structure were associated with the
      interference of the essential oils with the enzymes responsible for cell wall
      synthesis, which disturbed normal growth. Moreover, the essential oils caused
      high vacuolation of the cytoplasm, detachment of fibrillar layer of cell wall,
      plasma membrane disruption and disorganization of the nuclear and mitochondrial
      structures. Aspergillus fumigatus and A. flavus growth inhibition induced by
      these oils were found to be well-correlated with subsequent morphological changes
      of the fungi exposed to different fungistatic concentrations of the oils. Our
      results show the anti-Aspergillus activities of C. cyminum, Z. clinopodioides and
      N. sativa essential oils, which strengthens the potential use of these substances
      as anti-mould in the future. 

PMID- 24031625
TI  - Correlation between api 50 ch and multiplex polymerase chain reaction for the
      identification of vaginal lactobacilli in isolates.
AB  - Identification of Lactobacillus sp. strains by phenotypic methods may lead to
      doubtful results possibly interfering in the reliability of the epidemiological
      and probiotics studies. Therefore this study aimed to determine the best
      methodology for the identification of the large diversity of lactobacilli species
      found in the vagina by comparing two techniques, one based on their biochemical
      profile and other employing molecular biology. A carbohydrate fermentation test
      (API 50 CH) was compared with multiplex polymerase chain reaction (PCR) for the
      identification of species of vaginal lactobacilli from 135 healthy women. The
      kappa index was used to evaluate agreement between the methods. Using the
      molecular technique, L. crispatus (32.6%), L. jensenii (25%) and L. gasseri
      (20.6%) were the most frequent species. However, using the biochemical technique,
      the most frequent species were: L. acidophilus (34.8%), L. crispatus (27.2%) and
      L. fermentum (13%). Although L. acidophilus was the most frequent specie found by
      biochemical tests, no strain of this microorganism was detected by PCR. Agreement
      between the methods was low for identification of all the most common species.
      Although rates of L. crispatus detected were similar using both methods (32.6%
      and 27.2%), agreement between them was relatively low (kappa = 0.52).
      CONCLUSIONS: Our results confirmed the limitation of the biochemical method and
      the applicability of a previously published molecular method (Multiplex PCR) for
      the identification of lactobacilli in the vaginal tract, focusing on further
      necessity of its improvement for also targeting L. vaginalis and L. iners.

PMID- 24031626
TI  - Growth Inhibition and Morphological Alterations of Trichophyton Rubrum Induced by
      Essential oil from Cymbopogon Winterianus Jowitt Ex Bor.
AB  - Trichophyton rubrum is one of the most common fungi causer of dermatophytosis,
      mycosis that affect humans and animals around the world. Researches aiming new
      products with antifungal activity become necessary to overcome difficulties on
      treatment of these infections. Accordingly, this study aimed to investigate the
      antifungal activity of essential oil from Cymbopogon winterianus against the
      dermatophyte T. rubrum. The antifungal screening was performed by solid medium
      diffusion method with 16 T. rubrum strains, minimum inhibitory concentration
      (MIC) and minimum fungicide concentration (MFC) were determined using the
      microdilution method. The effects on mycelial dry weight and morphology were also
      observed. Screening showed essential oil in natura inhibited all the tested
      strains, with inhibition zones between 24-28 mm diameter. MIC50 and MIC90 values
      of the essential oil were 312 MUg/mL for nearly all the essayed strains (93.75 %)
      while the MFC50 and MFC90 values were about eight times higher than MIC for all
      tested strains. All tested essential oil concentrations managed to inhibit
      strongly the mycelium development. Main morphological changes on the fungal
      strains observed under light microscopy, which were provided by the essential oil
      include loss of conidiation, alterations concerning form and pigmentation of
      hyphae. In the oil presence, colonies showed folds, cream color and slightly
      darker than the control, pigment production was absent on the reverse and with
      evident folds. It is concluded that C. winterianus essential oil showed activity
      against T. rubrum. Therefore, it could be known as potential antifungal compound
      especially for protection against dermatophytosis. 

PMID- 24031627
TI  - The prevalence of enterotoxigenic e. Coli isolated from the stools of children
      aged 0-10 years with diarrhea in mid-anatolia region, Turkey.
AB  - The stool samples from 245 patients with diarrhea were tested for heat labile
      toxin (LT) and heat stable toxins (ST) by passive latex agglutination and enzyme
      immunoassay methods respectively. Twelve (4.9%) enterotoxigenic E. Coli ETEC
      strains were isolated. Five strains (2%) expressed ST, and 7 (2.8%) expressed LT.

PMID- 24031628
TI  - Prevalence, aetiology and antibiotic resistance profiles of coagulase negative
      staphylococci isolated in a teaching hospital.
AB  - In this paper we carried out a study about prevalence of the clinically
      significant coagulase negative staphylococcal (CNS) isolates found in an
      university hospital. Two hundred four CNS isolates from 191 patients obtained
      between the period of 1998 to 2002, were studied. About 27% (52/191) of the
      infection cases studied were confirmed as CNS-associated diseases. Blood stream
      infection (BSI) was the most frequent CNS associated-disease (25%; 13/52). The
      great majority of the BSI was verified in the Neonatal Intensive Care Unit
      (NICU). The analysis of the 52 patients medical history showed that 85% of the
      BSI was acquired in hospital. Most of the CNS nosocomial infections were
      associated with the use of indwelling medical devices. The incidence of
      methicillin-resistance among significant CNS isolates was 38%. In this study, a
      high percentage of exogenous contaminant was verified (60%), indicating that
      contamination of clinical specimens during sample collection is critical. 

PMID- 24031629
TI  - Antibiotic susceptibility profiles of Mycoplasma hominis and ureaplasma
      urealyticum isolated during a population-based study concerning women infertility
      in northeast romania.
AB  - The study was carried out on 1068 infertile women under initial evaluation. For
      Mycoplasma hominis, the highest resistance rates were registered for
      ciprofloxacin (72.22%), followed by macrolides and ofloxacin. For Ureaplasma
      urealyticum, the ciprofloxacin resistance was also high (51.72%), while the
      resistance rates to other tested antibiotics were significantly lower. 

PMID- 24031630
TI  - Campylobacter Insulaenigrae: First Isolation Report from South American sea lion
      (Otaria Flavescens, (Shaw, 1800).
AB  - Campylobacter insulaenigrae have been isolated from different pinnipeds but not
      from South American sea lion (Otaria flavescens).The aim of this work is to
      report the first isolation of C. insulaenigrae from South American sea lion
      (Otaria flavescens).The isolate, identified by its phenotypic and molecular
      characteristics, allow recognizing O. flavescens as a new host for C.
      insulaenigrae. 

PMID- 24031631
TI  - Behavior of salmonella heidelberg and salmonella enteritidis strains following
      broiler chick inoculation: evaluation of cecal morphometry, liver and cecum
      bacterial counts and fecal excretion patterns.
AB  - Over the years, Salmonella Heidelberg (SH) has gained prominence in North America
      poultry production and in the poultry production of other countries. Salmonella
      Heidelberg has been isolated and reported from poultry and poultry products in
      Brazil since 1962, whereas Salmonella Enteritidis (SE) has only emerged as a
      serious problem in poultry and public health since 1993. These strains of
      Salmonella can cause intestinal problems in newly hatched chicks, and infection
      may persist until adulthood. Upon slaughter of chickens, Salmonella can
      contaminate carcasses, a condition that poses a threat to human health. The aim
      of this study was to compare the fecal excretion of Salmonella Enteritidis and
      Salmonella Heidelberg in newly hatched chicks (orally inoculated with 10(5)ufc/mL
      each) until 20 days of age. In addition, the ratio of cecal villus height:crypt
      depth (morphometry) and liver and cecum cell counts was analyzed in chicks
      ranging from 0 to 3 days of age and infected with these two Salmonella strains.
      One hundred seventeen chicks were separated into one of three experimental
      groups: a control group, an SE-infected group and an SH-infected group. Eight
      chicks per group were euthanized at 6, 12 and 72 hours post-inoculation (pi) to
      allow for Salmonella isolation from the liver and cecum and for the collection of
      the cecum for villi and crypt analysis. Other birds were allowed to mature to 20
      days of age and cloacal swabs were taken at 2, 6, 13 and 20 days pi to compare
      the fecal excretion of inoculated strains. The Salmonella Enteritidis group had a
      higher number of cells excreted during the trial. Both strains were isolated from
      the liver and cecum by 6h pi. At 12h pi the Salmonella Heidelberg group had high
      cell counts in the cecum. No difference was found in liver cell counts. Both
      strains showed lower villus height:crypt depth ratio than the control group post
      infection. 

PMID- 24031632
TI  - The use of ozonized oil in the treatment of dermatophitosis caused by microsporum
      canis in rabbits.
AB  - The ozone is effective against most microorganisms due to its high oxidant power.
      Low concentrations and short-term contact are sufficient to inactivate bacteria,
      mold, yeast, parasites, seaweeds, protozoa and fungi. Microsporum canis is an
      important agent of dermatophitosis in human and animal. The aim of the current
      study was to assess the efficacy of ozonized oil over Microsporum canis in
      rabbits. Eighteen male New Zealand white rabbits, weight ranging from 2 to 3.2 kg
      were depilated in the cranial dorso-lateral and right caudal, and cranial and
      left caudal regions. The regions were inoculated with Microsporum canis,
      excepting the right caudal region, and were denominated TM, O, OM and M,
      respectively. After seven days, the treatment of lesions in TM began with 0.12g
      of terbinaphine 1% cream; in OM and O with 0.12g of ozonized oil; all animals
      were treated once a day for 28 days. Region M was not treated. Material was
      collected from those regions for cultivation in Sabouraud agar at day 28 of
      treatment. In the evolution of the treatment with terbinaphine, of 14
      contaminated regions with Microsporum canis ten evolved to cure. With the
      ozonized oil, of 15 contaminations, four were cured. Clinically, that is, the
      macroscopic evaluation of lesions showed improvement in the TM and OM treated
      regions. We can conclude that there was statistical evidence of the protection
      action of the oil against the dermatophyte. 

PMID- 24031633
TI  - Hematology and Productive Performance of Nile Tilapia (Oreochromis niloticus)
      Naturally Infected With Flavobacterium columnare.
AB  - Columnaris disease is one of the main causes of mortality in tilapia rearing and
      is responsible for large economic losses worldwide. Hematology is a tool that
      makes it possible to study organisms' physiological responses to pathogens. It
      may assist in making diagnoses and prognoses on diseases in fish populations. The
      hematological variables of nile tilapia were studied in specimens with a clinical
      diagnosis of columnaris disease and in specimens that were disease-free. The
      total erythrocyte count, hemoglobin rate, hematocrit percentage, mean corpuscular
      hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean
      corpuscular volume (MCV), organic defense blood cell percentages (leukocytes and
      thrombocytes) and hepatosomatic and splenosomatic index were determined. The
      results showed that there were changes in the erythrocytic series and in organic
      defense blood cells, in the fish infected with the bacterium, with reductions in
      erythrocytic variables and significant increases in the numbers of circulating
      lymphocytes and neutrophils. 

PMID- 24031634
TI  - Gastric helicobacter spp. Infection in captive neotropical brazilian feline.
AB  - Ten captive neotropical Brazilian feline were submitted to gastroscopic
      examination and samples of gastric mucosa from fundus, corpus and pyloric antrum
      were evaluated for the presence of Helicobacter species. Warthin-Starry (WS)
      staining and PCR assay with species-specific primers and enzymatic cleavage were
      applied for bacterial detection and identification. Histological lesions were
      evaluated by haematoxylin and eosin staining. All animals showed normal gross
      aspect of gastric mucosa. Helicobacter heilmannii was confirmed in 100% of the
      samples by WS and PCR assay. Mild lymphocytic infiltrate in the lamina propria
      was observed in eight animals, mainly in the fundus region. Small lymphoid
      follicles were seen in three animals. No significant association between
      Helicobacter infection and histological findings was verified. These observations
      suggest that gastric Helicobacter spp. could be a commensal or a eventual
      pathogen to captive neotropical feline, and that procedures, way life, and stress
      level on the shelter apparently had no negative repercussion over the integrity
      of the stomach. 

PMID- 24031635
TI  - Paralytic rabies in Swine.
AB  - Rabies transmitted by vampire bats was diagnosed in pigs with paralysis of the
      pelvic limbs. Diffuse non-suppurative encephalomyelitis, affecting mainly the
      spinal cord, was observed histologically. Despite the various diagnosis of rabies
      in pigs this is the first report of clinical signs and pathology of rabies
      transmitted by vampire bats. 

PMID- 24031636
TI  - Diagnostic Performance of an Immunoassay for Simultaneous Detection of Hcv Core
      Antigen and Antibodies among Haemodialysis Patients.
AB  - Nosocomial transmission of HCV is a concern in haemodialysis (HD) units
      worldwide. Diagnosis of HCV infection among dialysis patients is currently based
      on the detection of anti HCV antibodies by ELISA, and is confirmed by HCV RNA.
      The average window period between HCV infection and seroconversion with new
      generations of HCV antibody tests remains approximately 70 days with more
      prolonged period among dialysis patients. In this study we assessed the
      diagnostic performance of an immunoassay designed for simultaneous detection of
      anti HCV antibodies and core antigen in one step in comparison to qualitative RT
      PCR and anti HCV antibodies detection test among Egyptian haemodialysis patients.
      The studied patients were 39 chronic renal failure patients on maintenance
      haemodialysis. The results obtained in the present study revealed HCV infection
      of 56.4%. Combined Ag/Ab test detected 3 out of the 4 anti-HCV negative viraemic
      patients who were in the window period. The sensitivity, specificity and accuracy
      of the test were higher than that of anti HCV antibodies detection test (95.45%,
      94.1% and 94.87% versus 81.8%, 88.23% and 84.6%) and they were raised to 100% on
      combining its positivity with liver enzymes elevation results. Therefore, this
      simple combined Ag/Ab test can be applied for early detection of HCV infection
      during window period among HD patients as an alternative to HCV RNA detection. 

PMID- 24031637
TI  - Human T-Lymphotropic Virus (HTLV) Type I in vivo Integration in Oral
      Keratinocytes.
AB  - Although the infection of HTLV-1 to cell components of the mouth have been
      previously reported, there was not until this report, a detailed study to show
      the characteristics of such infection. From 14 Tropical Spastic Paraparesis/HTLV
      1-Associated Myelopathy (HAM/TSP) patients and 11 asymptomatic carrier
      individuals (AC) coming from HTLV-1 endemic areas of southwest Pacific of
      Colombia, infected oral mucosa cells were primary cultured during five days.
      These cell cultures were immunophenotyped by dual color fluorescence cell
      assortment using different lymphocyte CD markers and also were
      immunohistochemically processed using a polyclonal anti-keratin antibody. Five
      days old primary cultures were characterized as oral keratinocytes, whose
      phenotype was CD3- /CD4-/CD8-/CD19-/CD14-/CD45-/A575-keratin+. From DNA extracted
      of primary cultures LTR, pol, env and tax HTLV-1 proviral DNA regions were
      differentially amplified by PCR showing proviral integration. Using poly A+ RNA
      obtained of these primary cultures, we amplify by RT-PCR cDNA of tax and pol in
      57.14% (8/14) HAM/TSP patients and 27.28% (3/11) AC. Tax and pol poly A+ RNA were
      expressed only in those sIgA positive subjects. Our results showed that proviral
      integration and viral gene expression in oral keratinocytes are associated with a
      HTLV-1 specific local mucosal immune response only in those HTLV-1 infected
      individuals with detectable levels of sIgA in their oral fluids. Altogether the
      results gave strong evidence that oral mucosa infection would be parte of the
      systemic spreading of HTLV-1 infection. 

PMID- 24031638
TI  - Evaluation of a nested-PCR for mycobacterium tuberculosis detection in blood and
      urine samples.
AB  - The polymerase chain reaction (PCR) and its variations, such as the nested-PCR,
      have been described as promising techniques for rapid diagnosis of tuberculosis
      (TB). With the aim of evaluating the usefulness of a nested-PCR method on samples
      of blood and urine of patients suspected of tuberculosis we analyzed 192 clinical
      samples, using as a molecular target the insertion element IS6110 specific of M.
      tuberculosis genome. Nested-PCR method showed higher sensitivity in patients with
      extrapulmonary tuberculosis (47.8% and 52% in blood and urine) when compared to
      patients with the pulmonary form of the disease (sensitivity of 29% and 26.9% in
      blood and urine), regardless of the type of biological sample used. The nested
      PCR is a rapid technique that, even if not showing a good sensitivity, should be
      considered as a helpful tool especially in the extrapulmonary cases or in cases
      where confirmatory diagnosis is quite difficult to be achieved by routine
      methods. The performance of PCR-based techniques should be considered and tested
      in future works on other types of biological specimens besides sputum, like blood
      and urine, readily obtainable in most cases. The improving of M. tuberculosis
      nested-PCR detection in TB affected patients will give the possibility of an
      earlier detection of bacilli thus interrupting the transmission chain of the
      disease. 

PMID- 24031639
TI  - Lactobacillus Acidophilus-Derived Biosurfactant Effect on GTFB and GTFC
      Expression Level in Streptococcus Mutans Biofilm Cells.
AB  - Streptococcus mutans (S. mutans), harboring biofilm formation, considered as a
      main aetiological factor of dental caries. Gtf genes play an important role in S.
      mutans biofilm formation. The purpose of this study was to investigate the effect
      of Lactobacillus acidophilus-derived biosurfactant on S. mutans biofilm formation
      and gtfB/C expression level (S. mutans standard strain ATCC35668 and isolated S.
      mutans strain (22) from dental plaque). The Lactobacillus acidophilus (L.
      acidophilus) DSM 20079 was selected as a probiotic strain to produce
      biosurfactant. The FTIR analysis of its biosurfactant showed that it appears to
      have a protein-like component. Due to the release of such biosurfactants, L.
      acidophilus was able to interfere in the adhesion and biofilm formation of the S.
      mutans to glass slide. It also could make streptococcal chains shorter. Using
      realtime RT-PCR quantitation method made it clear that gtfB and gtfC gene
      expression were decreased in the presence of L. acidophilus-derived biosurfactant
      fraction. Several properties of S. mutans cells (the surface properties, biofilm
      formation, adhesion ability and gene expression) were changed after L.
      acidophilus- derived biosurfactant treatment. It is also concluded that
      biosurfacant treatment can provide an optional way to control biofilm
      development. On the basis of our findings, we can suggest that the prepared
      biosurfactant may interfere with adhesion processes of S. mutans to teeth
      surfaces, provided additional evaluation produce satisfactory results. 

PMID- 24031640
TI  - Structural analysis of human respiratory syncytial virus p protein:
      identification of intrinsically disordered domains.
AB  - Human Respiratory Syncytial Virus P protein plus the viral RNA, N and L viral
      proteins, constitute the viral replication complex. In this report we describe
      that HRSV P protein has putative intrinsically disordered domains predicted by in
      silico methods. These two domains, located at the amino and caboxi terminus, were
      identified by mass spectrometry analysis of peptides obtained from degradation
      fragments observed in purified P protein expressed in bacteria. The degradation
      is not occurring at the central oligomerization domain, since we also demonstrate
      that the purified fragments are able to oligomerize, similarly to the protein
      expressed in cells infected by HRSV. Disordered domains can play a role in
      protein interaction, and the present data contribute to the comprehension of HRSV
      P protein interactions in the viral replication complex. 

PMID- 24031641
TI  - Vegetative Compatibility and Heterokaryon Formation between Different Isolates of
      Colletotrichum Lindemuthianum by using the nit Mutant System.
AB  - Colletotrichum lindemuthianum, the causative agent of bean anthracnose, is one of
      the most common pathogens leading to expressive damage to plants beyond
      presenting noticeable variability. The knowledge on vegetative compatibility
      groups (VCGs) is of particular interest in asexual fungi as they subdivide the
      population in groups that can exchange genetic information via heterokaryosis and
      the parasexual cycle. Among the techniques used in studies about vegetative
      compatibility groups, the obtainment of nit mutants is apparent. This paper is
      aimed at obtaining heterokaryons between different isolates of C. lindemuthianum,
      grouping them in VCGs and evaluating their genetic variability by using the nit
      mutants system. Nit mutants were obtained from 20 single spore isolates. The
      mutants were phenotypically classified and paired for complementation and
      formation of heterokaryons so as to group them in VCGs. Seventeen mutants from
      the different phenotypic-rates were recovered: nit1, nit2, nit3 and nitM. At the
      same time, 10 mutants were selected for pairing and division of the anastomosis
      groups. Nine heterokaryons were obtained and the isolates were divided into 9
      vegetative compatibility groups. In the combinations for the formation of
      anastomosis, 31 compatible combinations and 24 incompatible combinations were
      observed. It was concluded that the methodology used to select nit mutants in C.
      lindemuthianum made it possible to determine the vegetative compatibility groups
      and that such a technique was adequate to prove genetic variability. 

PMID- 24031642
TI  - Biological Activities of a Mixture of Biosurfactant from Bacillus subtilis and
      Alkaline Lipase from Fusarium oxysporum.
AB  - In this study, we investigate the antimicrobial effects of a mixture of a
      biosurfactant from Bacillus subtilis and an alkaline lipase from Fusarium
      oxysporum (AL/BS mix) on several types of microorganisms, as well as their
      abilities to remove Listeria innocua ATCC 33093 biofilm from stainless steel
      coupons. The AL/BS mix had a surface tension of around 30 mN.m(-1), indicating
      that the presence of alkaline lipase did not interfere in the surface activity
      properties of the tensoactive component. The antimicrobial activity of the AL/BS
      mix was determined by minimum inhibitory concentration (MIC) micro-assays. Among
      all the tested organisms, the presence of the mixture only affected the growth of
      B. subtilis CCT 2576, B. cereus ATCC 10876 and L. innocua. The most sensitive
      microorganism was B. cereus (MIC 0.013 mg.mL(-1)). In addition, the effect of the
      sanitizer against L. innocua attached to stainless steel coupons was determined
      by plate count after vortexing. The results showed that the presence of the AL/BS
      mix improved the removal of adhered cells relative to treatment done without the
      sanitizer, reducing the count of viable cells by 1.72 log CFU.cm(-2). However,
      there was no significant difference between the sanitizers tested and an SDS
      detergent standard (p<0.05). 

PMID- 24031643
TI  - Growth and content of spirulina platensis biomass chlorophyll cultivated at
      different values of light intensity and temperature using different nitrogen
      sources.
AB  - The effects of light intensity and temperature in S. platensis cultivation with
      potassium nitrate or urea as nitrogen source were investigated, as well as the
      biomass chlorophyll contents of this cyanobacteria, through the Response Surface
      Methodology. Experiments were performed at temperatures from 25 to 34.5oC and
      light intensities from 15 to 69 umol photons m(-2) s(-1), in mineral medium. In
      cultivations with both sources of nitrogen, KNO3 and urea, statistic evaluation
      through multiple regression, no interactions of such independent variables were
      detected in the results of the dependent variables maximum cell concentration,
      chlorophyll biomass contents, cell and chlorophyll productivities, as well as in
      the nitrogen-cell conversion factor. In cultivation performed with both sources
      of nitrogen, it was possible to obtain satisfactory adjustments to relate the
      dependent variables to the independent variables. The best results were achieved
      at temperature of 30oC, at light intensity of 60 umol photons m(-2)s(-1), for
      cell growth, with cell productivity of approximately 95 mg L(-1) d(-1) in
      cultivations with urea. For the chlorophyll biomass content, the most adequate
      light intensity was 24 umol photons m(-2) s(-1). 

PMID- 24031644
TI  - Tannase Production by Penicillium Atramentosum KM under SSF and its Applications
      in Wine Clarification and Tea Cream Solubilization.
AB  - Tannin acyl hydrolase commonly known as tannase is an industrially important
      enzyme having a wide range of applications, so there is always a scope for novel
      tannase with better characteristics. A newly isolated tannase-yielding fungal
      strain identified as Penicillium atramentosum KM was used for tannase production
      under solid-state fermentation (SSF) using different agro residues like amla
      (Phyllanthus emblica), ber (Zyzyphus mauritiana), jamun (Syzygium cumini), Jamoa
      (Eugenia cuspidate) and keekar (Acacia nilotica) leaves. Among these substrates,
      maximal extracellular tannase production i.e. 170.75 U/gds and 165.56 U/gds was
      obtained with jamun and keekar leaves respectively at 28oC after 96 h. A
      substrate to distilled water ratio of 1:2 (w/v) was found to be the best for
      tannase production. Supplementation of sodium nitrate (NaNO3) as nitrogen source
      had enhanced tannase production both in jamun and keekar leaves. Applications of
      the enzyme were studied in wine clarification and tea cream solubilization. It
      resulted in 38.05% reduction of tannic acid content in case of jamun wine, 43.59%
      reduction in case of grape wine and 74% reduction in the tea extract after 3 h at
      35 degrees C. 

PMID- 24031645
TI  - Kinetic analysis of batch ethanol acetylation in isothermal non-stationary
      multiphase systems by lyophilized mycelium of Aspergillus oryzae.
AB  - A relatively complex network of reactions has been investigated, using as a
      network model the isothermal batch esterification of acetic acid with ethanol in
      n-heptane catalyzed by lyophilized mycelium of Aspergillus oryzae. The kinetic
      analysis was firstly carried out on the whole system, without any simplification,
      by means of the well-known integral method. Owing to the poor results obtained by
      this way, we developed an alternative approach, combining initial rates and
      integral analysis and reducing the number of empirical parameters to be
      determined by the use of equilibrium data. All the values of the parameters
      calculated according to this "composite" approach to kinetic analysis well
      correlate with experimental data. 

PMID- 24031646
TI  - Citric Acid production from orange peel wastes by solid-state fermentation.
AB  - Valencia orange (Citrus sinensis) peel was employed in this work as raw material
      for the production of citric acid (CA) by solid-state fermentation (SSF) of
      Aspergillus niger CECT-2090 (ATCC 9142, NRRL 599) in Erlenmeyer flasks. To
      investigate the effects of the main operating variables, the inoculum
      concentration was varied in the range 0.5.10(3) to 0.7.10(8) spores/g dry orange
      peel, the bed loading from 1.0 to 4.8 g of dry orange peel (corresponding to 35
      80 % of the total volume), and the moisture content between 50 and 100 % of the
      maximum water retention capacity (MWRC) of the material. Moreover, additional
      experiments were done adding methanol or water in different proportions and ways.
      The optimal conditions for CA production revealed to be an inoculum of 0.5.10(6)
      spores/g dry orange peel, a bed loading of 1.0 g of dry orange peel, and a
      humidification pattern of 70 % MWRC at the beginning of the incubation with
      posterior addition of 0.12 mL H2O/g dry orange peel (corresponding to 3.3 % of
      the MWRC) every 12 h starting from 62 h. The addition of methanol was detrimental
      for the CA production. Under these conditions, the SSF ensured an effective
      specific production of CA (193 mg CA/g dry orange peel), corresponding to yields
      of product on total initial and consumed sugars (glucose, fructose and sucrose)
      of 376 and 383 mg CA/g, respectively. These results, which demonstrate the
      viability of the CA production by SSF from orange peel without addition of other
      nutrients, could be of interest to possible, future industrial applications. 

PMID- 24031647
TI  - The Exploration of the Antibacterial Mechanism of FE(3+) against Bacteria.
AB  - This study demonstrated that the bacteria could adsorb Fe(3+) and reduce Fe(3+)
      to Fe(2+). Iron had significant bacteriostatic effects, which were directly
      proportional to the iron concentration and under the influence of pH and
      chelator. It presumed that the inhibition of Fe(3+) acts through the formation of
      hydroxyl free radicals. 

PMID- 24031648
TI  - Multiresistance and endemic status of acinetobacter baumannii associated with
      nosocomial infections in a tunisian hospital: a critical situation in the
      intensive care units.
AB  - Acinetobacter baumannii is often implicated in hospital outbreaks in Tunisia.
      It's a significant opportunistic pathogen associated with serious underlying
      diseases such as pneumoniae, meningitis and urinary tract infections. The aim of
      our study was to evaluate its degree of endemicity and its antibiotic resistance
      evolution essentially in the unit care where its isolation was predominant (57%).
      This study used 3 methods: antibiotyping, RAPD using 2 primers VIL 1, VIL5 and
      PFGE with ApaI restriction enzyme. The presence of integron1 and 2 was also
      studied. Antibiotyping showed that 92% of patients were resistant of all beta-
      lactams (except Imipenem) and that the resistance to Imipenem occurred in 47% of
      cases. RAPD profiles obtained with the 2 arbitrarily primers VIL1 and VIL5 gave
      respectively 5 and 4groups and PFGE fingerprinting patterns revealed 22 different
      pulsotypes. Integron 1 was present in 25% of unrelated strains and type 2
      integron was not detected in any of the studied strains. Among 204 strains,
      multiple and heterogeneous groups were detected with the genomic studies. In
      addition, any correlation was obtained with the antibiotyping results. These
      findings demonstrate the endemic status of A. baumannii in our hospital and the
      persistence of a large number of multiresistant strains in the unit's care. When
      outbreaks of A. baumannii occur, it's essential to develop restricted hygiene
      procedures and a serious surveillance of critical units such as ICU for very ill
      patients. 

PMID- 24031649
TI  - A quantitative analysis of Propionibacterium acnes in lesional and non-lesional
      skin of patients with progressive macular hypomelanosis by real-time polymerase
      chain reaction.
AB  - Little is known about the etiology of progressive macular hypomelanosis, although
      it has been suggested that Propionibacterium acnes plays an important role. While
      microbiological culture is commonly employed to identify Propionibacterium acnes,
      new identification methods have been under investigation, amongst them polymerase
      chain reaction. To determine the cut-off point for the number of genome copies of
      Propionibacterium acnes in the lesional skin of patients with progressive macular
      hypomelanosis as a positive marker, employing quantitative real-time polymerase
      chain reaction and anaerobic culture, considered gold standard. An observational
      study with a comparison group, included 35 patients with dermatosis, attended at
      the Oswaldo Cruz University Hospital, Pernambuco, Brazil, between March and May
      2008. Lesional skin was compared to non-lesional skin through positive testing
      with real-time polymerase chain reaction and culture. The Statistical Package for
      Social Sciences, version 12.0, was employed for the association analysis with the
      McNemar test, and the cut-off point with the ROC curve for maximum values.
      Propionibacterium acnes was most frequently encountered in lesional areas
      (p<0,025). The cut-off point of Propionibacterium acnes in lesional skin was
      1,333 genome copies, with a sensitivity of 87,9% and a specificity of 100,0%.
      Since Propionibacterium acnes is a saprophyte, identifying the cut-off point may
      assist in determining its positivity in lesional skin in patients suffering with
      this dermatosis. 

PMID- 24031650
TI  - Detection of Bartonella henselae in defibrinated sheep blood used for culture
      media supplementation.
AB  - Bartonella henselae was detected in defibrinated sheep blood employed in
      supplementing a selective bacteria culture medium by nested PCR. We recommended
      that highly sensitive technical tests be run to ensure a sterile culture medium
      for Bartonella spp. isolation, since infected blood samples used in preparation
      could lead to false-positive results. 

PMID- 24031651
TI  - Antifungal activity of Cymbopogon winterianus jowitt ex bor against Candida
      albicans.
AB  - Candida albicans is an opportunistic yeast and a member of the normal human flora
      that commonly causes infections in patients with any type of deficiency of the
      immune system. The essential oils have been tested for antimycotic activity and
      pose much potential as antifungal agents. This work investigated the activity of
      the essential oil of Cymbopogon winterianus against C. albicans by MIC, MFC and
      time-kill methods. The essential oil (EO) was obtained by hydrodistillation using
      a Clevenger-type apparatus. It was tested fifteen strains of C. albicans. The MIC
      was determined by the microdilution method and the MFC was determined when an
      aliquot of the broth microdilution was cultivated in SDA medium. The
      phytochemical analysis of EO showed presence of citronellal (23,59%), geraniol
      (18,81%) and citronellol (11,74%). The EO showed antifungal activity, and the
      concentrations 625 ug/mL and 1250 ug/mL inhibited the growth of all strains
      tested and it was fungicidal, respectively. The antimicrobial activity of various
      concentrations of EO was analyzed over time, it was found concentration-dependent
      antifungal activity, whose behavior was similar to amphotericin B and nystatin. 

PMID- 24031652
TI  - Isolation of Helicobacter pylori in gastric mucosa and susceptibility to five
      antimicrobial drugs in Southern chile.
AB  - Helicobacter pylori colonizes more than 50% of the world population thus, it is
      considered an important cause of gastric cancer. The aim of this study was to
      determine the isolation frequency of H. pylori in Southern Chile from patients
      with symptomatology compatible with gastritis or gastric ulcer and to correlate
      these findings with demographic parameters of infected patients and the
      susceptibility profiles of the isolated strains to the antimicrobial drugs used
      in the eradication treatments. A total of 240 patients were enrolled in the
      study. Each gastric biopsy was homogenized and seeded onto blood agar plates
      containing a selective antibiotics mixture (DENT supplement). Plates were
      incubated at 37 degrees  C in a microaerophilic environment for five days. The
      susceptibility profiles to amoxicillin, ciprofloxacin, clarithromycin,
      tetracycline and metronidazole were determined using the E-test method. H. pylori
      was isolated from 99 patients (41.3%) with slightly higher frequency in female
      (42% positive cultures) than male (40.2% positive cultures). With regard to age
      and educational level, the highest isolation frequencies were obtained in
      patients between 21-30 (55%) and 41-50 (52.6%) years old, and patients with
      secondary (43.9%) and university (46.2%) educational levels. Nineteen (21.6%)
      strains showed resistance to at least one antimicrobial drug. Tetracycline was
      the most active antimicrobial in vitro, whereas metronidazole was the less
      active. One strain (5.3%) showed resistance to amoxicillin, clarithomycin and
      metronidazole, simultaneously. 

PMID- 24031653
TI  - Development of conventional and real-time multiplex PCR assays for the detection
      of nosocomial pathogens.
AB  - Nosocomial infections are major clinical threats to hospitalised patients and
      represent an important source of morbidity and mortality. It is necessary to
      develop rapid detection assays of nosocomial pathogens for better prognosis and
      initiation of antimicrobial therapy in patients. In this study, we present the
      development of molecular methods for the detection of six common nosocomial
      pathogens including Escherichia coli, Staphylococcus aureus, Streptococcus
      pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp.
      Conventional multiplex PCR and SYBR Green based real time PCR assays were
      performed using genus and species specific primers. Blind testing with 300
      clinical samples was also carried out. The two assays were found to be sensitive
      and specific. Eubacterial PCR assay exhibited positive results for 46 clinical
      isolates from which 43 samples were detected by real time PCR assay. The
      sensitivity of the assay is about 93.7% in blind test isolates. The PCR results
      were reconfirmed using the conventional culture method. This assay has the
      potential to be a rapid, accurate and highly sensitive molecular diagnostic tool
      for simultaneous detection of Escherichia coli, Staphylococcus aureus,
      Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa and
      Acinetobacter spp. This assay has the potential to detect nosocomial pathogens
      within 5 to 6 hours, helping to initiate infection control measures and
      appropriate treatment in paediatric and elderly (old aged) patients, pre-and post
      surgery patients and organ transplant patients and thus reduces their
      hospitalization duration. 

PMID- 24031654
TI  - Nasal rhinosporiodiosis from uttar pradesh (India). a non-endemic zone: first
      case report.
AB  - Rhinosporiodiosis is a cosmopolitan disease of man and animals, endemic in India
      and Sri Lanka with main focus of infection in Southern Tamil Nadu. Uttar Pradesh
      (UP) is not known to be an endemic zone for this disease .We present here the
      first case of nasal Rhinosporiodiosis from this non-endemic zone. 

PMID- 24031655
TI  - Prevalence of antimicrobial resistance and integrons in Escherichia coli from
      Punjab, Pakistan.
AB  - Antimicrobial resistance was studied in Escherichia coli strains isolated from
      urine samples of 457 patients suffering from urinary tract infection. High
      prevalence of class 1 integrons (43.56%), sulfamethoxazole resistance genes sul1
      (45.54%) and sul2 (51.48%) along with occurrence of quinolone resistance genes
      was detected in multi drug resistance isolates. 

PMID- 24031656
TI  - Resistance of Klebsiella Pneumoniae clinical isolates: linkage of outer membrane
      proteins (omps) with production esbls.
AB  - Three isolates of Klebsiella pneumoniae, collected from the University Hospital
      in Fortaleza, Brazil, were analyzed to determine their resistance to multiple
      antibiotics. The results of this study showed that the resistance of the
      clinically isolated bacteria is associated with the production of extended
      spectrum beta-lactamases (ESLBs) and loss of outer membrane proteins. 

PMID- 24031657
TI  - New antimicrobial combinations: substituted chalcones- oxacillin against
      methicillin resistant Staphylococcus aureus.
AB  - Staphylococcus aureus, the most virulent Staphylococcus species, is also the
      prevalent pathogen isolated from hospitalized patients and the second most common
      from patients in outpatient settings. In general, bacteria have the genetic
      ability to transmit and acquire resistance to drugs, which are utilized as
      therapeutic agents. Related studies of antimicrobial activity indicate that crude
      extracts containing flavonoids, triterpenes and steroids have showed
      significative activity against several Staphylococcus aureus strains. Combination
      effects between flavonoids and antibiotics also have been reported. The aim of
      the present work was to investigate in vitro synergism between several chalcones
      substituted in combination with oxacillin, an antibiotic used conventionally
      against S. aureus ATCC 43 300 that is resistant to meticillin, using the kinetic
      turbidimetric method developed earlier. The results were satisfactory for all
      assayed combinations and in accordance with the mechanism of bacteriostatic
      inhibition previously proposed, except for 2',4'-dihydroxy-3'-methoxychalcone -
      oxacillin. The best combination was 2',3'-dihydroxychalcone -oxacillin (MIC: 11.2
      ug/mL). Further investigations are needed to characterize the interaction
      mechanism with antibiotics. Thus, chalcones - oxacillin combination could lead to
      the development of new antibiotics against methicillin resistant S. aureus
      infection. 

PMID- 24031658
TI  - Evaluation of biofilm production by Pseudomonas Aeruginosa isolates recovered
      from cystic fibrosis and non-cystic fibrosis patients.
AB  - Cystic fibrosis (CF) patients typically suffer of persistent and recurrent lung
      infections caused by Pseudomonas aeruginosa that many times possess ability for
      the biofilm production. Here, biofilm production among P. aeruginosa isolates
      recovered from sputum of CF and non-CF patients was evaluated. Most isolates were
      biofilm-producing independently of the patient's condition. 

PMID- 24031659
TI  - Species distribution and antimicrobial susceptibility of enterococci isolated
      from broilers infected experimentally with Eimeria spp and fed with diets
      containing different supplements.
AB  - Resistant bacteria in animal can be spread to environment and to humans. Poultry
      feed and infections caused by Eimeria spp. are important factors in determining
      the intestinal microbial communities. The aim of this study was to verify the
      prevalence of species and antimicrobial susceptibility of Enterococcus isolated
      from broilers fed with different supplements and infected experimentally with
      Eimeria spp. Broilers were divided in eight groups, fed with diets supplemented
      with a combination of antimicrobial, ionophore-coccidiostatics, probiotic,
      essential oil. At 14 days old all birds, except the control, received a solution
      containing oocysts of Eimeria spp. Samples of cloacal swabs from broilers were
      collected. A total of 240 Enterococcus sp. strains were isolated, confirmed genus
      by PCR, classified as species, tested for antimicrobial susceptibility and
      screened by PCR for the presence of tet(L), tet(M) and erm(B) genes. The overall
      distribution of species isolated from fecal samples was E. faecalis (40%),
      followed by E. casseliflavus/E. gallinarum (10.8%), E. mundtii (10.8%), E.
      faecium (10.8%), E. columbae (5.8%) and E. gallinarum (4.2%). Changes in the
      composition or frequency of Enterococcus species were observed in all dietary
      supplementation. Antimicrobial susceptibility tests showed resistance phenotypes
      a range of antibiotics, especially used in humans such as, streptomycin,
      penicillin, rifampicin and vancomycin. There was no correlation between different
      supplementation for broilers and antimicrobial resistance and the presence of
      tet(M), tet(L) and erm(B) genes. Dietary supplementation had effect on the
      Enterococcus sp. colonization, but did not have significant effect on the
      phenotype and genotype of antimicrobial resistance in enterococci. 

PMID- 24031660
TI  - The hydrophobicity and roughness of a nasoenteral tube surface influences the
      adhesion of a multi-drug resistant strain of Staphylococcus Aureus.
AB  - IN THIS STUDY, WE EXAMINED THE PHYSIOCHEMICAL PROPERTIES OF NASOENTERAL FEEDING
      TUBES MADE FROM TWO DIFFERENT TYPES OF POLYMER: silicone materials and
      polyurethane. The internal surfaces of the nasoenteral feeding tubes were
      analyzed for their hydrophobicity, roughness, microtopography, rupture-tension
      and ability to stretch. We also studied the adhesion of an isolated, multi-drug
      resistant strain of S. aureus to these polymers. The polyurethane nasoenteral
      tube, which was classified as hydrophilic, was more resistant to rupture-tension
      and stretching tests than the silicone tube, which was classified as hydrophobic.
      Additionally, the polyurethane tube had a rougher surface than the silicone tube.
      Approximately 1.0 log CFU.cm(-2) of S. aureus cells adhered to the tubes and this
      number was not statistically different between the two types of surfaces (p >
      0.05). In future studies, new polymers for nasoenteral feeding tubes should be
      tested for their ability to support bacterial growth. Bacterial adhesion to these
      polymers can easily be reduced through modification of the polymer's
      physicochemical surface characteristics. 

PMID- 24031661
TI  - Effect of culture medium on biocalcification by Pseudomonas Putida,
      Lysinibacillus Sphaericus and Bacillus Subtilis.
AB  - The objective of this study is to investigate the efficiency of calcium carbonate
      bioprecipitation by Lysinibacillus sphaericus, Bacillus subtilis and Pseudomonas
      putida, obtained from the Colecao de Culturas do Instituto Nacional de Controle
      de Qualidade em Saude (INCQS), as a first step in determining their potential to
      protect building materials against water uptake. Two culture media were studied:
      modified B4 containing calcium acetate and 295 with calcium chloride. Calcium
      consumption in the two media after incubation with and without the bacterial
      inoculum was determined by atomic absorption analysis. Modified B4 gave the best
      results and in this medium Pseudomonas putida INQCS 113 produced the highest
      calcium carbonate precipitation, followed by Lysinibacillus sphaericus INQCS 414;
      the lowest precipitation was produced by Bacillus subtilis INQCS 328. In this
      culture medium XRD analysis showed that Pseudomonas putida and Bacillus subtilis
      precipitated calcite and vaterite polymorphs while Lysinibacillus sphaericus
      produced only vaterite. The shape and size of the crystals were affected by
      culture medium, bacterial strain and culture conditions, static or shaken. In
      conclusion, of the three strains Pseudomonas putida INQCS 113 in modified B4
      medium gave the best results precipitating 96% of the calcium, this strain thus
      has good potential for use on building materials. 

PMID- 24031662
TI  - Inoculation of tomato seedlings with Trichoderma Harzianum and Arbuscular
      Mycorrhizal Fungi and their effect on growth and control of wilt in tomato
      seedlings.
AB  - A green house study was conducted to investigate the ability of an isolate of
      Trichoderma harzianum (P52) and arbuscular mycorrhizal fungi (AMF) in enhancing
      growth and control of a wilt pathogen caused by Fusarium oxysporum f. sp.
      lycopersici in tomato seedlings. The plants were grown in plastic pots filled
      with sterilized soils. There were four treatments applied as follows; P52, AMF,
      AMF + P52 and a control. A completely randomized design was used and growth
      measurements and disease assessment taken after 3, 6 and 9 weeks. Treatments that
      significantly (P < 0.05) enhanced heights and root dry weights were P52, AMF and
      a treatment with a combination of both P52 and AMF when compared the control. The
      treatment with both P52 and AMF significantly (P < 0.05) enhanced all growth
      parameters (heights; shoot and root dry weight) investigated compared to the
      control. Disease severity was generally lower in tomato plants grown with isolate
      P52 and AMF fungi either individually or when combined together, though the
      effect was not statistically significant (P>= 0.05). A treatment combination of
      P52 + AMF had less trend of severity as compared to each individual fungus. T.
      harzianum and AMF can be used to enhance growth in tomato seedlings. 

PMID- 24031663
TI  - A novel acidophilic, thermophilic iron and sulfur-oxidizing archaeon isolated
      from a hot spring of tengchong, yunnan, China.
AB  - A novel thermoacidophilic iron and sulfur-oxidizing archaeon, strain YN25, was
      isolated from an in situ enriched acid hot spring sample collected in Yunnan,
      China. Cells were irregular cocci, about 0.9-1.02 um * 1.0-1.31 um in the medium
      containing elemental sulfur and 1.5-2.22 um * 1.8-2.54 um in ferrous sulfate
      medium. The ranges of growth and pH were 50-85 (optimum 65) and pH 1.0-6.0
      (optimum 1.5-2.5). The acidophile was able to grow heterotrophically on several
      organic substrates, including various monosaccharides, alcohols and amino acids,
      though the growth on single substrate required yeast extract as growth factor.
      Growth occurred under aerobic conditions or via anaerobic respiration using
      elemental sulfur as terminal electron acceptor. Results of morphology,
      physiology, fatty acid analysis and analysis based on 16S rRNA gene sequence
      indicated that the strain YN25 should be grouped in the species Acidianus
      manzaensis. Bioleaching experiments indicated that this strain had excellent
      leaching capacity, with a copper yielding ratio up to 79.16% in 24 d. The type
      strain YN25 was deposited in China Center for Type Culture Collection
      (=CCTCCZNDX0050). 

PMID- 24031664
TI  - Enterobacteriaceae in mouth and cloaca of podocnemis expansa and P. Unifilis
      (testudines: chelonia) populations of national park of araguaia plains, Brazil.
AB  - Shigella flexnerii and Escherichia coli were the most frequent Gram-negative
      bacteria found in the mouth cavity and cloacae of the turtles Podocnemis expansa
      and P. unifilis on beaches in the National Park of Araguaia, Brazil. Reptiles are
      known as Salmonella carriers, despite rarely isolated in these turtles. 

PMID- 24031665
TI  - Conservation tillage, optimal water and organic nutrient supply enhance soil
      microbial activities during wheat (Triticum Aestivum L.) cultivation.
AB  - The field experiments were conducted on sandy loam soil at New Delhi, during 2007
      and 2008 to investigate the effect of conservation tillage, irrigation regimes
      (sub-optimal, optimal and supra-optimal water regimes), and integrated nutrient
      management (INM) practices on soil biological parameters in wheat cultivation.
      The conservation tillage soils has shown significant (p<0.05) increase in soil
      respiration (81.1%), soil microbial biomass carbon (SMBC) (104%) and soil
      dehydrogenase (DH) (59.2%) compared to the conventional tillage soil. Optimum
      water supply (3-irrigations) enhanced soil respiration over sub-optimum and supra
      optimum irrigations by 13.32% and 79% respectively. Soil dehydrogenase (DH)
      activity in optimum water regime has also increased by 23.33% and 8.18%
      respectively over the other two irrigation regimes. Similarly, SMBC has also
      increased by 12.14% and 27.17% respectively in soil with optimum water supply
      compared to that of sub-optimum and supra-optimum water regime fields. The
      maximum increase in soil microbial activities is found when sole organic source
      (50% Farm Yard Manure+25% biofertilizer+25% Green Manure) has been used in
      combination with the conservation tillage and the optimum water supply. Study
      demonstrated that microbial activity could be regulated by tillage, water and
      nitrogen management in the soil in a sustainable manner. 

PMID- 24031666
TI  - The osmoprotective effect of some organic solutes on Streptomyces sp. mado2 and
      nocardiopsis sp. mado3 growth.
AB  - The response of two marine actinomycetes such as Streptomyces sp. MADO2 and
      Nocardiopsis sp. MADO3 to osmotic stress in minimal medium M63 and in glycerol
      asparagine medium (ISP5) was studied. The two strains were moderately halophilic
      and the behavior of the strain Streptomyces sp. MADO2 and Nocardiopsis sp. MADO3
      towards the salt stress was varied depends on the media composition and the
      salinity concentration. The strain Streptomyces sp. was more sensitive to salt
      stress than Nocardiopsis sp. The growth of both Streptomyces sp. and Nocardiopsis
      sp. were inhibited at 1 M NaCl irrespective of the medium used. The Nocardiopsis
      sp. acquired osmoadaptation on ISP5 medium whereas the Streptomyces sp. showed
      poor growth on M63 medium. Glycine betaine (GB), proline and trehalose played a
      critical role in osmotic adaptation at high osmolarity whereas at low osmolarity
      they showed an inhibitory effect on the bacterial growth. The present findings
      confirmed that GB was the powerful osmoprotectant for Streptomyces sp. and
      Nocardiopsis sp. grown at 1 M NaCl both in M63 and ISP5 media. 

PMID- 24031667
TI  - Microbiological monitoring of mineral water commercialized in Brazil.
AB  - The quality of mineral water commercialized in Brazil regarding the microbial
      content was analyzed and the results were compared with the standards established
      by the current legislation. Results demonstrated there was no bacterial
      contamination, but several types of fungi were found. Therefore, bottled mineral
      water could be considered a possible route for the transmission of filamentous
      fungi and yeasts. 

PMID- 24031668
TI  - Quality of water sources used as drinking water in a Brazilian peri-urban area.
AB  - The objective of this paper was to assess bacteriological quality of drinking
      water in a peri-urban area located in the Metropolitan Region of Sao Paulo,
      Brazil. A total of 89 water samples were collected from community plastic tanks
      and 177 water samples from wells were collected bimonthly, from September 2007 to
      November 2008, for evaluating bacteriological parameters including: Escherichia
      coli, Enterococcus and heterotrophic plate count (HPC). Clostridium perfringens
      was investigated in a subsample (40 samples from community plastic tank and 40
      from wells). E. coli was present in 5 (5.6%) samples from community plastic tanks
      (2.0 - 5.1x10(4) MPN/100mL) and in 70 (39.5%) well samples (2.0 - 8.6x10(4)
      MPN/100mL). Thus, these samples were not in accordance with the Brazilian
      Regulation. Enterococcus was detected in 20 (22.5%) samples of the community
      plastic tanks (1 to 79 NC/100mL) and in 142 (80.2%) well samples (1 to >200
      NC/100mL). C. perfringens was detected in 5 (12.5%) community plastic tanks
      samples and in 35 (87.5%) wells samples (2.2 to >16 MPN/100mL). HPC were above
      500 CFU/mL in 5 (5.6%) waters from community plastic tanks. In wells samples, the
      HPC ranged from <1 to 1.6x10(4) CFU/mL. The residual chlorine did not attend the
      standard established in the drinking water legislation (0.2 mg/L), except in 20
      (22.5%) samples. These results confirm the vulnerability of the water supply
      systems in this peri-urban area what is clearly a public health concern. 

PMID- 24031669
TI  - Identification and characterization of the endophytic plant growth prompter
      Bacillus Cereus strain mq23 isolated from Sophora Alopecuroides root nodules.
AB  - Endophytes MQ23 and MQ23R isolated from Sophora alopecuroides root nodules were
      characterized by observing their ability to promote plant growth and employing
      molecular analysis techniques. Results showed that MQ23 and MQ23R are potential
      N2-fixing endophytes and belong to the same species as Bacillus cereus. MQ23 was
      shown to be able to produce siderophores, IAA, and demonstrate certain antifungal
      activity to plant pathogenic fungi. Co-inoculation with MQ23+MQ23II showed a more
      significant effect than inoculation alone in vitro for most of positive actions
      suggesting they have a cooperative interaction. Results of plant inoculation with
      endophytes indicated that the growth indexes of co-inoculated MQ23+MQ23II were
      higher than those of inoculated alone (p<0.05) (the exception being for root
      fresh weight) when compared to negative control. There have been little of any
      studies of nonrhizobial putative endophytes with growth-promotion attributes in
      S. alopecuroides root nodules. This could be exploited as potential bio
      inoculants and biocontrol agents in agriculture. 

PMID- 24031670
TI  - Quick adaptation of Ralstonia Solanacearum to copper stress to recover
      culturability and growth in water and soil.
AB  - Cells of Ralstonia solanacearum were exposed to Cu in distilled water, and the
      resulting Cu-stressed non-culturable cells were inoculated to natural (non
      pasteurized) and pasteurized soils in order to examine their culturability and
      recovery. Exposing the cells to 20 MUM CuSO4 produced transitory non-culturable
      cells, which exhibited a remarkable recovery in culturability after incubation in
      the solution for 36 h, reaching a density near the initial level by 108 h. To
      determine whether such non-culturable cells actually "resuscitated" or multiplied
      after adapting to Cu toxicity, growth curves were constructed in order to
      contrast the rates of increase in culturable cell numbers between Cu-stressed or
      non-stressed inocula. Additionally, fresh non-stressed cells were exposed to
      CuSO4 in the presence of nalidixic acid by adding the antibiotic at different
      times after the onset of Cu stress to verify any cell multiplication during the
      population increase. The results revealed that the non-culturable cells surviving
      Cu toxicity adapted very quickly to Cu and began multiplying within 12 h, because
      only the Cu-stressed cells that were increasing in the exponential growth phase,
      but not those in the stationary phase, were killed by the antibiotic. Such cells
      exhibited an apparent tolerance to this metal when inoculated to a freshly
      prepared solution of CuSO4, and also detoxified the ion in the solution in which
      they grew. The presence of nutrients greatly counteracted the effect of Cu in
      water microcosms, since culturable cells were detected and increased in number
      even when exposed to 40 MUM CuSO4. In contrast, when inoculated to non
      pasteurized soil, Cu-stressed cells showed no such recoveries. However, when the
      soil was pasteurized before inoculation or added with nutrients, culturable cells
      were recovered and increased in number. This indicates that increased nutrient
      availability in soil allows Cu-stressed cells to quickly overcome the stress and
      increase in culturable populations. 

PMID- 24031671
TI  - Identification, isolation and optimization of antifungal metabolites from the
      Streptomyces Malachitofuscus ctf9.
AB  - An indigenous Streptomyces isolate CTF9, exhibiting promising antifungal activity
      against Mucor miehei and Candida albicans in pre-screening studies, was
      investigated by cultivation in a 50-L fermenter and by subsequent isolation,
      purification, and structure elucidation of the active metabolites. Based on the
      morphological, biochemical, and physiological characterization, as well as the
      16S rRNA gene sequence, the isolate CTF9 was identified as Streptomyces
      malachitofuscus. Using a series of chromatographic techniques, two pure compounds
      were isolated from the obtained extracts after the fermentation of the isolate
      CTF9. The isolated compounds were identified as phenylacetic acid and indolyl-3
      lactic acid by mass spectrometry (MS) and NMR analysis. The culture optimization
      studies revealed that the isolate CTF9 can use a variety of low-cost carbon and
      nitrogen sources to generate the maximum quantity of industrially important
      metabolites at an elevated temperature of 35 degrees C and at a pH 7.8. 

PMID- 24031672
TI  - "A comparison between sugar consumption and ethanol production in wort by
      immobilized Saccharomyces Cerevisiae, Saccharomyces Ludwigii and Saccharomyces
      Rouxii on Brewer'S Spent Grain".
AB  - The immobilization of Saccharomyces cerevisiae DSM 70424, Saccharomyces ludwigii
      DSM 3447 and Saccharomyces rouxii DSM 2531 on brewer's spent grain and then
      ethanol production and sugar consumption of these immobilized yeasts were
      investigated. The aim of this study was to investigate the abilities of these
      three immobilized yeasts for producing alcohol for brewing at two temperatures (7
      and 12  degrees C) using two different sugar levels (one at original level
      supplied in the brewery and one with 2.5% (w/v), added glucose to the wort).
      Increasing both parameters resulted in higher alcohol production by all the
      yeasts studied. At 7  degrees C and with original wort density the ethanol
      content at the end of fermentation was 2.7% (v/v) for S. cerevisiae, 1.7% for S.
      ludwigii and 2.0% for S. rouxii. After the addition of 2.5% (w/v) glucose at the
      same temperature (7  degrees C), the alcohol production was increased to 4.1, 2.8
      and 4.1%, respectively. Similar improvements were observed when the fermentation
      was carried out at 12  degrees C with/without the addition of glucose to the
      wort. However, temperature indicated greater influence on S. ludwigii than did on
      S. rouxii and S. cerevisiae. The immobilization as carried out in this study
      impacted both S. ludwigii and S. rouxii in a way that they could consume maltose
      under certain conditions. 

PMID- 24031673
TI  - Production flush of Agaricus blazei on Brazilian casing layers.
AB  - This study aimed to verify the biological efficiency and production flushes of
      Agaricus blazei strains on different casing layers during 90 cultivation days.
      Four casing layers were used: mixture of subsoil and charcoal (VCS), lime schist
      (LSC), Sao Paulo peat (SPP) and Santa Catarina peat (SCP); and two genetically
      distant A. blazei strains. The fungus was grown in composted substratum and,
      after total colonization, a pasteurized casing layer was added over the
      substratum, and fructification was induced. Mushrooms were picked up daily when
      the basidiocarp veil was stretched, but before the lamella were exposed. The
      biological efficiency (BE) was determined by the fresh basidiocarp mass divided
      by the substratum dry mass, expressed in percentage. The production flushes were
      also determined over time production. The BE and production flushes during 90
      days were affected by the strains as well as by the casing layers. The ABL26 and
      LSC produced the best BE of 60.4%. Although VCS is the most used casing layer in
      Brazil, it is inferior to other casing layers, for all strains, throughout
      cultivation time. The strain, not the casing layer, is responsible for eventual
      variations of the average mushroom mass. In average, circa 50% of the mushroom
      production occurs around the first month, 30% in the second month, and 20% in
      third month. The casing layer water management depends on the casing layer type
      and the strain. Production flush responds better to water reposition, mainly with
      ABL26, and better porosity to LSC and SCP casing layers. 

PMID- 24031674
TI  - Growth of the Ectomycorrhizal Fungus Pisolithus Microcarpus in different
      nutritional conditions.
AB  - The most important plant species employed in reforestation programs depend on
      ectomycorrhizal fungi for their establishment and growth. The exploitation of
      this symbiosis to improve forest productivity requires fungal inoculants in a
      large scale level. To develop such a technology it is necessary to define the
      optimal composition of the culture medium for each fungus. With these objectives
      in mind, the effect of the composition of the culture medium on biomass
      production of the ectomycorrhizal fungus Pisolithus microcarpus (isolate UFSC
      Pt116) was studied. The original composition of two culture media, already
      employed for cultivation of ectomycorrhizal fungi, was submitted to several
      variations with the C/N ratio as the main variable. A variation of the Pridham
      Gottlieb medium was the most efficient for the production of biomass. Therefore,
      it was submitted to a factorial assay where glucose, peptone and yeast extract
      components were the factors analyzed. Results showed that the glucose
      concentration may be increased up to 40 % in order to promote higher biomass
      production. Peptone had a positive effect on this variable, whereas yeast extract
      promoted a deleterious effect. These results indicate that it is advisable to
      eliminate yeast extract from the medium and replace it with peptone prior to use.

PMID- 24031675
TI  - Comparative study of two purified inulinases from thermophile Thielavia
      Terrestris NRRL 8126 and mesophile Aspergillus Foetidus NRRL 337 grown on
      Cichorium Intybus l.
AB  - Thirty fungal species grown on Cichorium intybus L. root extract as a sole carbon
      source, were screened for the production of exo-inulinase activities. The
      thermophile Thielavia terrestris NRRL 8126 and mesophile Aspergillus foetidus
      NRRL 337 gave the highest production levels of inulinases I & II at 50 and 24 oC
      respectively. Yeast extract and peptone were the best nitrogen sources for
      highest production of inulinases I & II at five and seven days of incubation
      respectively. The two inulinases I & II were purified to homogeneity by gel
      filtration and ion-exchange chromatography with 66.0 and 42.0 fold of
      purification respectively. The optimum temperatures of purified inulinases I & II
      were 75 and 50 oC respectively. Inulinase I was more thermostable than the other
      one. The optimum pH for activity was found to be 4.5 and 5.5 for inulinases I &
      II respectively. A comparatively lower Michaelis-Menten constant (2.15 mg/ml) and
      higher maximum initial velocity (115 umol/min/mg of protein) for inulinase I on
      inulin demonstrated the exoinulinase's greater affinity for inulin substrate.
      These findings are significant for its potential industrial application. The
      molecular mass of the inulinases I & II were estimated to be 72 & 78 kDa
      respectively by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 

PMID- 24031676
TI  - Identification of the bacterial community responsible for traditional
      fermentation during sour cassava starch, cachaca and minas cheese production
      using culture-independent 16s rRNA gene sequence analysis.
AB  - We used a cultivation-independent, clone library-based 16S rRNA gene sequence
      analysis to identify bacterial communities present during traditional
      fermentation in sour cassava starch, cachaca and cheese production in Brazil.
      Partial 16S rRNA gene clone sequences from sour cassava starch samples collected
      on day five of the fermentation process indicated that Leuconostoc citreum was
      the most prevalent species, representing 47.6% of the clones. After 27 days of
      fermentation, clones (GenBank accession numbers GQ999786 and GQ999788) related to
      unculturable bacteria were the most prevalent, representing 43.8% of the clones
      from the bacterial community analyzed. The clone represented by the sequence
      GQ999786 was the most prevalent at the end of the fermentation period. The
      majority of clones obtained from cachaca samples during the fermentation of sugar
      cane juice were from the genus Lactobacillus. Lactobacillus nagelli was the most
      prevalent at the beginning of the fermentation process, representing 76.9% of the
      clones analyzed. After 21 days, Lactobacillus harbinensis was the most prevalent
      species, representing 75% of the total clones. At the end of the fermentation
      period, Lactobacillus buchneri was the most prevalent species, representing 57.9%
      of the total clones. In the Minas cheese samples, Lactococcus lactis was the most
      prevalent species after seven days of ripening. After 60 days of ripening,
      Streptococcus salivarius was the most prevalent species. Our data show that these
      three fermentation processes are conducted by a succession of bacterial species,
      of which lactic acid bacteria are the most prevalent. 

PMID- 24031677
TI  - Optimization of clavulanic acid production by Streptomyces daufpe 3060 by
      response surface methodology.
AB  - Clavulanic acid is a beta-lactam antibiotic which has a potent beta-lactamase
      inhibiting activity. In order to optimize its production by the new isolate
      Streptomyces DAUFPE 3060, the influence of two independent variables, temperature
      and soybean flour concentration, on clavulanic acid and biomass concentrations
      was investigated in 250 mL-Erlenmeyers according to a 2(2) central composite
      design. To this purpose, temperature and soybean flour (SF) concentration were
      varied in the ranges 26-34 degrees C and 10-50 g/L, respectively, and the results
      evaluated utilizing the Response Surface Methodology. The experimental maximum
      production of clavulanic acid (629 mg/L) was obtained at 32 degrees C and 40 g/L
      SF after 48 h, while the maximum biomass concentration (3.9 g/L) at 30 degrees C
      and 50 g/L soybean flour, respectively. These values are satisfactorily close to
      those (640 mg/L and 3.75 g/L, respectively) predicted by the model, thereby
      demonstrating the validity of the mathematical approach adopted in this study.

PMID- 24031678
TI  - Isolation and characterization of a Pichia anomala strain: a promising candidate
      for bioethanol production.
AB  - A yeast strain designated as Y-1 was isolated and characterized from wine yeast
      ("Jiuqu"). Based on the morphological and biochemical results, along with the
      rDNA internal transcribed spacer region (ITS), Y-1 was identified to be a Pichia
      anomala strain. Y-1 is an ethanol-tolerant strain, enduring ethanol
      concentrations of up to 14 %. Y-1 growth medium conditions were optimized,
      results showing good growth in medium with pH ranges from 3.5-6.5, temperature
      ranges from 25-30  degrees C, and inoculums range of 8 %-12 %, while optimum
      growth conditions were reached at a temperature of 30  degrees C, pH 5.0, and
      inoculums of 10 %. Furthermore, when the alkaline hydrolyzed Shatian pummelo peel
      solutions were inoculated with 10 % Y-1 and fermented at 30  degrees C for 6 d,
      4.7 % pure ethanol (w/w) was produced, as evidenced by gas chromatography
      analysis. Our present study shows potential for the Y-1 strain to be a promising
      candidate for bioethanol production. 

PMID- 24031679
TI  - Continuous ethanol production using immobilized yeast cells entrapped in loofa
      reinforced alginate carriers.
AB  - A culture of Saccharomyces cerevisiae M30 entrapped in loofa-reinforced alginate
      was used for continuous ethanol fermentation in a packed-bed reactor with initial
      sugar concentrations of 200-248 g/L. Maximum ethanol productivity of 11.5 g/(L.h)
      was obtained at an ethanol concentration of 57.4 g/L, an initial sugar
      concentration of 220 g/L and a dilution rate (D) of 0.2 h(-1). However, a maximum
      ethanol concentration of 82.1 g/L (productivity of 9.0 g/(L.h)) was obtained at a
      D of 0.11 h(-1). Ethanol productivity in the continuous culture was 6-8-fold
      higher than that in the batch culture. Due to the developed carrier's high
      biocompatibility, high porosity, and good mechanical strength, advantages such as
      cell regeneration, reusability, altered mechanical strength, and high capacity to
      trap active cells in the reactor were achieved in this study. The immobilized
      cell reactor was successfully operated for 30 days without any loss in ethanol
      productivity. The average conversion yield was 0.43-0.45 throughout the entire
      operation, with an immobilization yield of 47.5%. The final total cell
      concentration in the reactor was 37.3 g/L (17.7 g/L immobilized cells and 19.6
      g/L suspended cells). The concentration of suspended cells in the effluent was
      0.8 g/L. 

PMID- 24031680
TI  - Characterization of class 1 integrons and antibiotic resistance genes in
      multidrug-resistant Salmonella enterica isolates from foodstuff and related
      sources.
AB  - In recent years, an increase in the occurrence of antimicrobial resistance among
      Salmonella enterica has been observed in several countries, which is worrisome
      because S. enterica is one of the most common causes of human gastroenteritis
      worldwide. The aim of this study was to characterize class 1 integrons and
      antibiotic resistance genotypes in Salmonella enterica isolates recovered from
      foodstuff and related sources. Nineteen multidrug-resistant (MDR) Salmonella
      enterica isolates were recovered. Higher resistance rates to tetracycline (90%),
      streptomycin (80%), sulfamethoxazole-trimethoprim (80%), ampicillin (60%) and
      nalidixic acid (70%) were related to the presence of the tetA, aadA, sul1/sul2,
      bla TEM-1 genes, and a codon mutation at position 83 of the gyrA gene,
      respectively. Class 1 integrons harboring aadA, bla TEM-1, sul1 or dhfr1 genes
      were detected in nine (45%) Salmonella enterica strains belonging to serotypes
      Brandenburg, Panama, Agona, Mbandaka and Alachua. Finally, clonal dissemination
      of S. Panama, S. Derby and S. Mbandaka was confirmed by PFGE. Detection of
      clonally related MDR Salmonella enterica suggests that endemic serotypes can be
      supported by class 1 integron-borne gene cassettes and/or mutations in drug
      targets. Emergence and dissemination of multidrug-resistant Salmonella enterica
      can have a major public health impact in an environment where large-scale
      suppliers ship their products. 

PMID- 24031681
TI  - Brazilian kefir: structure, microbial communities and chemical composition.
AB  - Microbial ecology and chemical composition of Brazilian kefir beverage was
      performed. The microorganisms associated with Brazilian kefir were investigated
      using a combination of phenotypic and genotypic methods. A total of 359 microbial
      isolates were identified. Lactic acid bacteria (60.5%) were the major isolated
      group identified, followed by yeasts (30.6%) and acetic acid bacteria (8.9%).
      Lactobacillus paracasei (89 isolates), Lactobacillus parabuchneri (41 isolates),
      Lactobacillus casei (32 isolates), Lactobacillus kefiri (31 isolates),
      Lactococcus lactis (24 isolates), Acetobacter lovaniensis (32 isolates),
      Kluyveromyces lactis (31 isolates), Kazachstania aerobia (23 isolates),
      Saccharomyces cerevisiae (41 isolates) and Lachancea meyersii (15 isolates) were
      the microbial species isolated. Scanning electron microscopy showed that the
      microbiota was dominated by bacilli (short and curved long) cells growing in
      close association with lemon-shaped yeasts cells. During the 24 h of
      fermentation, the protein content increased, while lactose and fat content
      decreased. The concentration of lactic acid ranged from 1.4 to 17.4 mg/ml, and
      that of acetic acid increased from 2.1 to 2.73 mg/ml. The production of ethanol
      was limited, reaching a final mean value of 0.5 mg/ml. 

PMID- 24031682
TI  - Arcobacter butzleri: first isolation report from chicken carcasses in costa rica.
AB  - Arcobacter butzleri isolation from chicken carcasses in Costa Rica is reported
      for the first time. The isolated strains (P and R) were presumptively identified
      by their phenotypic characteristics. Definitive identification was made using a
      multiplex PCR assay for the simultaneous detection and identification of
      Arcobacter butzleri, Arcobacter cryaerophilus and Arcobacter skirrowii. These
      first isolations indicate the necessity of further investigation about the
      prevalence, distribution, ecology and interactions with human beings of this and
      other Arcobacter species. 

PMID- 24031683
TI  - The neem [Azadirachta indica a. juss (meliaceae)] oil reduction in the in vitro
      production of zearalenone by Fusarium graminearum.
AB  - Zearalenone, a mycotoxin produced by fungi of the genus Fusarium, including F.
      graminearum, triggers reproduction disorders in certain animals and hyperestrogen
      syndromes in humans. Current research investigates three concentrations of neem
      oil extract (0.1, 0.25 and 0.5%) in reducing the production of zearalenone. Neem
      oil extract decreased zearalenone amount in the three concentrations but highest
      inhibition (59.05%) occurred at 0.1%. 

PMID- 24031684
TI  - Occurrence of subtilase cytotoxin and relation with other virulence factors in
      verocytotoxigenic Escherichia coli isolated from food and cattle in Argentina.
AB  - We investigated the presence of the gene of subtilase cytotoxin (SubAB),
      described in certain highly virulent verocytotoxigenic E. coli strains, in
      isolates from Argentina and its relation with other virulence factors. The gene
      subA was present in eae-negative strains mostly associated with saa, vt2 and ehxA
      genes. 

PMID- 24031685
TI  - Optimization of media components for enhanced production of streptococcus phocae
      pi80 and its bacteriocin using response surface methodology.
AB  - The standard MRS components were optimized using response surface methodology for
      increasing yield of Streptococcus phocae PI80 viable cells and its bacteriocin.
      The highest amounts of bacteriocin activity and viable cells were recorded from
      prediction point of optimized MRS medium and achieved two fold higher (33049.8
      AU.mL(-1) and 14.05 LogCFU.mL(-1)) than un-optimized counterpart. 

PMID- 24031686
TI  - Mycoplasmas hyorhinis in different regions of cuba. diagnosis.
AB  - M. hyorhinis is considered one of the etiological agents of arthritis in sucking
      pigs, but recently as seen, some strains can produce pneumonia that could not be
      distinguished from the mycoplasmosis caused by M. hyopneumoniae. The study was
      conducted to research the presence of Mycoplasma hyorhinis (M. hyorhinis ) in
      different regions of the country from exudates of pig lungs with typical EP
      lesions. Exudates from 280 pig lungs with typical EP lesions were studied using
      molecular techniques such as PCR, real time PCR and amplification of the 16S-23S
      rRNA. It was detected that the 66% of the samples studied resulted positive to M.
      hyorhinis, and the presence of this species was detected in all the provinces.
      Amplification and studies on the intergenic region 16S-23S of M. hyorhinis rRNA
      demonstrated the existing variability among strains of a same species. This study
      is the first report on M. hyorhinis detection in Cuba. 

PMID- 24031687
TI  - Tuberculosis determined by Mycobacterium bovis in captive waterbucks (Kobus
      ellipsiprymnus) in SAo paulo, Brazil.
AB  - Two waterbucks from Sao Paulo Zoo Foundation exhibited respiratory symptoms in
      July 2004. After euthanasia, granulommas in lungs and mediastinic lymph nodes
      were observed. Acid-fast bacilli isolated were identified as Mycobacterium bovis
      spoligotype SB0121 by PRA and spoligotyping. They were born and kept in the same
      enclosure with the same group, without any contact to other species housed in the
      zoo. This is the first detailed description of M. bovis infection in Kobus
      ellipsiprymnus. 

PMID- 24031688
TI  - Production of reactive oxygen (H2O2) and nitrogen (NO) intermediates and tnf
      alpha in mice genetically selected for high (H) and low (L) antibody response and
      experimentally infected with Leptospira serovar pomona.
AB  - The aim of the present study was to evaluate the activity of macrophages, and the
      production of TNF-alpha and antibodies against experimental infection by
      Leptospira serovar Pomona in mice genetically selected for High (H) or Low (L)
      humoral immune response. To evaluate macrophagic activity, peritoneal and splenic
      lavages were performed for determination of oxygen (H2O2) and nitrogen (NO)
      intermediates. The production of the tumor necrosis factor (TNF-alpha) was
      investigated through bioassays in serum and homogenates of splenic and hepatic
      cells of control and infected animals, as was as specific antibodies production.
      The immune response against serovar Pomona in those lines, was characterized by
      high antibody production, especially in later periods of the infectious process,
      whereas values of bacterial recovery in culture medium were lower. The production
      of reactives oxygen and nitrogen intermediate, also helped to eliminate
      Leptospira Pomona in both lines; H2O2 production an important factor in HIV-A, as
      well as NO production in LIV-A, especially in later post-inoculation periods. The
      same was detected for TNF-alpha. Results suggest that such lines could be an
      important model to investigate the pathogenesis and the immune response of
      animals against the several Leptospira serovars. 

PMID- 24031689
TI  - Identification and antimicrobial resistance of microflora colonizing feral pig
      (Sus scrofa) of Brazilian Pantanal.
AB  - Antimicrobial resistance of bacteria is a worldwide problem affecting wild life
      by living with resistant bacteria in the environment. This study presents a
      discussion of outside factors environment on microflora of feral pigs (Sus
      scrofa) from Brazilian Pantanal. Animals had samples collected from six different
      body sites coming from two separated geographic areas, Nhecolandia and Rio Negro
      regions. With routine biochemical tests and commercial kits 516 bacteria were
      identified, with 240 Gram-positive, predominantly staphylococci (36) and
      enterococci (186) strains. Among Gram-negative (GN) bacteria the predominant
      specimens of Enterobacteriaceae (247) mainly represented by Serratia spp. (105),
      Escherichia coli (50), and Enterobacter spp. (40) and specimens not identified
      (7). Antimicrobial susceptibility was tested against 17 drugs by agar diffusion
      method. Staphylococci were negative to production of enterotoxins and TSST-1,
      with all strains sensitive towards four drugs and highest resistance toward
      ampicillin (17%). Enterococci presented the highest sensitivity against
      vancomycin (98%), ampicillin (94%) and tetracycline (90%), and highest resistance
      pattern toward oxacillin (99%), clindamycin (83%), and cotrimoxazole (54%). In GN
      the highest resistance was observed with Serratia marcescens against CFL (98%),
      AMC (66%) and AMP (60%) and all drugs was most effective against E. coli SUT, TET
      (100%), AMP, TOB (98%), GEN, CLO (95%), CFO, CIP (93%). The results show a new
      profile of oxacillin-resistant enterococci from Brazilian feral pigs and suggest
      a limited residue and spreading of antimicrobials in the environment, possibly
      because of low anthropogenic impact reflected by the drug susceptibility profile
      of bacteria isolated. 

PMID- 24031690
TI  - Immune response to dna vaccine expressing transferrin binding protein a gene of
      Pasteurella multocida.
AB  - Haemorrhagic Septicaemia (HS), an acute and fatal disease of cattle and buffalo
      is primarily caused by serotype B:2 or E:2 of Pasteurella multocida. The
      transferrin binding protein A (TbpA) has been found to act as immunogen and
      potent vaccine candidate in various Gram negative bacteria including P.
      multocida. The present study was carried out to evaluate the potential of this
      antigen as a DNA vaccine against HS in mice model. The tbpA gene of P. multocida
      serotype B:2 was cloned in a mammalian expression vector alone and along with
      murine IL2 gene as immunological adjuvant to produce monocistronic and
      bicistronic DNA vaccine constructs, respectively. The immune response to DNA
      vaccines was evaluated based on serum antibody titres and lymphocyte
      proliferation assay. A significant increase in humoral and cell mediated immune
      responses was observed in mice vaccinated with DNA vaccines as compared to non
      immunized group. Additionally, the bicistronic DNA vaccine provided superior
      immune response and protection level following challenge as compared to
      monocistronic construct. The study revealed that DNA vaccine presents a promising
      approach for the prevention of HS. 

PMID- 24031691
TI  - Identification of fungi of the genus Aspergillus section nigri using polyphasic
      taxonomy.
AB  - In spite of the taxonomy of the Aspergillus species of the Nigri Section being
      regarded as troublesome, a number of methods have been proposed to aid in the
      classification of this Section. This work aimed to distinguish Aspergillus
      species of the Nigri Section from foods, grains and caves on the basis in
      Polyphasic Taxonomy by utilizing morphologic and physiologic characters, and
      sequencing of beta-tubulin and calmodulin genes. The morphologic identification
      proved useful for some species, such as A. carbonarius and Aspergillus sp UFLA
      DCA 01, despite not having been totally effective in elucidating species related
      to A. niger. The isolation of the species of the Nigri Section on Creatine
      Sucrose Agar (CREA) enabled to distinguish the Aspergillus sp species, which was
      characterized by the lack of sporulation and by the production of sclerotia.
      Scanning Electron microscopy (SEM) allowed distinguishing the species into two
      distinct groups. The production of Ochratoxin A (OTA) was only found in the A.
      carbonarius and A. niger species. The sequencing of beta-tubulin gene was
      efficient in differing most of the Aspergillus species from the Nigri Section
      with the exception of Aspergillus UFLA DCA 01, which could not be distinguished
      from A. costaricaensis. This species is morphologically similar to A.
      costaricaencis for its low sporulation capacity and high sclerotia production,
      but it differs morphologically from A. costaricaensis for its conidial
      ornamentation and size of vesicles. Equally, based on partial calmodulin gene
      sequence data Aspergillus UFLA DCA 01 differs from A. costaricaensis. 

PMID- 24031692
TI  - Assessment of the quality of dna extracted by two techniques from Mycobacterium
      tuberculosis for fast molecular identification and genotyping.
AB  - We report a comparative study of two DNA extraction techniques, thermolysis and
      chemical lysis (CTAB), for molecular identification and genotyping of M.
      tuberculosis. Forty DNA samples were subjected to PCR and the results
      demonstrated that with thermolysis it is possible to obtain useful data that
      enables fast identification and genotyping. 

PMID- 24031693
TI  - Variations in the sensitivity of different primers for detecting Wolbachia in
      Anastrepha (diptera: tephritidae).
AB  - Wolbachia are endosymbiont bacteria of the family Rickettsiacea that are
      widespread in invertebrates and occur between 20% and 60% of Neotropical insects.
      These bacteria are responsible for reproductive phenomena such as cytoplasmic
      incompatibility, male killing, feminization and parthenogenesis. Supergroups A
      and B of Wolbachia are common in insects and can be identified using primers for
      16S rDNA, ftsZ and wsp; these primers vary in their ability to detect Wolbachia.
      The ftsZ primer was the first primer used to detect Wolbachia in Anastrepha fruit
      flies. The primers for 16S rDNA, ftsZ and wsp and the corresponding PCR
      conditions have been optimized to study the distribution of Wolbachia and their
      effect on the biology of Anastrepha in Brazil. In this work, we examined the
      ability of these primers to detect Wolbachia in Anastrepha populations from three
      regions in the State of Sao Paulo, southeastern Brazil. All of the samples were
      positive for Wolbachia supergroup A when screened with primers for 16S A rDNA and
      wsp A; the wsp B primer also gave a positive result, indicating cross-reactivity.
      The ftsZ primer showed a poor ability to detect Wolbachia in Anastrepha and
      generated false negatives in 44.9% of the samples. These findings indicate that
      reliable PCR detection of Wolbachia requires the use of primers for 16S rDNA and
      wsp to avoid cross-reactions and false negatives, and that the ftsZ primer needs
      to be redesigned to improve its selectivity. 

PMID- 24031694
TI  - Diversity and uncommon HPV types in HIV seropositive and seronegative women
      attending an STI clinic.
AB  - Given the causal relationship between specific types of HPV with cervical cancer
      and precursor lesions, it is important to identify the viral type involved. The
      aim of this study is to access the prevalence of HPV types in HIV seropositive
      and seronegative women. Accordingly, 77 HPV positive cervical samples were
      obtained from 284 women (seropositive (n=112) and seronegative (n=172) for HIV)
      who attended a Sexually Transmitted Infection clinic, in Vitoria, Southeastern
      Brazil. Viral DNA was amplified by PCR using MY09/MY11 degenerated primers and
      the genotyping was performed by Restriction Fragment Length Polymorphism. Seventy
      five out of the 77 HPV samples were genotyped: 6, 11, 13, 16, 18, 26, 31, 31b,
      32, 33, 34, 35, 52, 53, 55, 56, 58, 59, 61, 62, 64, 66, 71, 81, 83, 84. The most
      prevalent type was HPV16 followed by HPV types 6, 11 and 53. Fifty five percent
      and 45% belonged to high and low risk types, respectively. High risk types
      corresponded to 59% and 54.5% of the HPV detected in HIV seronegative and
      seropositive women, respectively. The uncommon HPV 13 type in cervical samples
      was also observed in this study. The oncogenic types were more common in the HIV
      seronegative samples and the number of cases with multiple infections was similar
      for the two groups. HPV typing is not only important clinically for the
      establishment of monitoring and treatment of a patient, it also provides
      knowledge of the viral types circulating in a population, which is of interest in
      the development of prevention and treatment programs for this disease. 

PMID- 24031695
TI  - Screening and optimization of pectin lyase and polygalacturonase activity from
      ginseng pathogen Cylindrocarpon Destructans.
AB  - Cylindrocarpon destructans isolated from ginseng field was found to produce
      pectinolytic enzymes. A Taguchi's orthogonal array experimental design was
      applied to optimize the preliminary production of polygalacturonase (PG) and
      pectin lyase (PL) using submerged culture condition. This method was applied to
      evaluate the significant parameters for the production of enzymes. The process
      variables were pH, pectin concentration, incubation time and temperature.
      Optimization of process parameters resulted in high levels of enzyme (PG and PL)
      production after ten days of incubation at a pH of 5.0 at 25 degrees C in the
      presence of 1.5% pectin. Among different nitrogen sources, urea and peptone
      showed high production of PG and PL, respectively. The enzyme production and
      mycelial growth seems to have direct influence on the culture conditions;
      therefore, at stationary state high enzyme production and mycelial growth were
      obtained than agitation state. Along with this, optimization of enzyme activity
      was also determined using various physiological parameters like, temperature,
      incubation time and pH. Taguchi's data was also analyzed using one step ANOVA
      statistical method. 

PMID- 24031696
TI  - Mycobacterium avium subsp. Paratuberculosis and the expression of selected
      virulence and pathogenesis genes in response to 6 degrees C, 65 degrees c and ph
      2.0.
AB  - The aim of this work was to study the expression of selected Mycobacterium avium
      subsp. paratuberculosis (MAP) genes connected with MAP virulence, adhesion and
      stress response. The temperature of 6 degrees C and 65 degrees C were chosen with
      regard to the food industry, storage conditions (refrigerator) and low
      temperature pasteurization. A pH of 2.0, using lactic acid, was selected to mimic
      the natural environment of the stomach. Expression of selected genes was studied
      using real time reverse transcription PCR on three different MAP isolates. MAP
      isolates were chosen according to the number of their preceding cultivations.
      While isolates 8672 and 8819 were previously cultivated only once, MAP isolate
      12146 went through four passages. Different expression profiles were observed in
      each of the three MAP isolates. However, particular similar patterns were
      observed. SigE, sigF and ahpC were up-regulated, while sigL was down-regulated
      under temperature stress. Mmp gene was found to be down-regulated under acidic
      conditions. Low passage isolates (8672 and 8819) showed certain level of acid
      resistance. 

PMID- 24031697
TI  - Optimization of growth medium for protease production by Haloferax Lucentensis
      VKMM 007 by response surface methodology.
AB  - The production of halophilic thermostable protease by Haloferax lucentensis VKMM
      007 was optimized using a statistical approach. In accordance with factorial
      design, soluble starch, gelatin, KCl and MgSO4 were selected among 27 variables
      tested. Next, a second-order quadratic model was estimated and optimal medium
      concentrations were determined based on quadratic regression equation generated
      by model. These were 5.14 g L(-1) of KCl, 6.57 g L(-1)of MgSO4, 9.05 g L(-1)of
      gelatin and 5.27 g L(-1)of soluble starch in high salts media supplemented with
      0.5% (w/v) of beef extract and peptone, respectively. In these optimal
      conditions, the obtained protease concentration of 6.80 U mL(-1) was in agreement
      with the predicted protease concentration and was further improved to 7.02 U mL(
      1) by increasing the concentration of NaCl in the medium to 25% (w/v). An overall
      4.0-fold increase in protease production was achieved in the optimized medium
      compared to activity obtained in initial medium. 

PMID- 24031698
TI  - Formulation of economical microbial feed using degraded chicken feathers by a
      novel Streptomyces sp: mitigation of environmental pollution.
AB  - A new Streptomyces sp. IF 5 was isolated from the feather dumped soil and found
      to have a tremendous keratinase activity. The strain enabled the degradation of
      the chicken feathers very effectively in 60 h. The 16S rRNA sequence of 1474 bp
      long was submitted to the National centre for Biotechnological information. The
      keratinolytic activity in the culture medium was 1181 U/ml. The release and
      analyses of sulphydryl groups in the culture medium evident the degradation
      activity by the Streptomyces sp. IF 5. The idea of the present study was to use
      the degraded chicken feathers as the substrate for the growth and cultivation of
      microorganisms. We have designed a very economical culture medium that includes
      the usage of some basal salts alone and degraded chicken feathers (10 g/l). The
      results of the specific growth rate of the tested microbes confirm the usage of
      the new designed medium for microbial culturing. 

PMID- 24031699
TI  - Taxonomic study and partial characterization of antimicrobial compounds from a
      moderately halophilic strain of the genus Actinoalloteichus.
AB  - A moderately halophilic actinomycete strain designated AH97 was isolated from a
      saline Saharan soil, and selected for its antimicrobial activities against
      bacteria and fungi. The AH97 strain was identified by morphological,
      chemotaxonomic and phylogenetic analyses to the genus Actinoalloteichus. Analysis
      of the 16S rDNA sequence of strain AH97 showed a similarity level ranging between
      95.8% and 98.4% within Actinoalloteichus species, with A. hymeniacidonis the most
      closely related. The comparison of the physiological characteristics of AH97 with
      those of known species of Actinoalloteichus showed significant differences.
      Strain AH97 showed an antibacterial and antifungal activity against broad
      spectrum of microorganisms known to be human and plant pathogens. The bioactive
      compounds were extracted from the filtrate culture with n-butanol and purified
      using thin layer chromatography and high pressure liquid chromatography
      procedures. Two active products were isolated, one hydrophilic fraction (F1) and
      another hydrophobic (F2). Ultraviolet-visible, infrared, mass and (1)H and (13)C
      nuclear magnetic resonance spectroscopy studies suggested that these molecules
      were the dioctyl phthalate (F2) and an aminoglycosidic compound (F1). 

PMID- 24031700
TI  - Characterization of free nitrogen fixing bacteria of the genus Azotobacter in
      organic vegetable-grown Colombian soils.
AB  - With the purpose of isolating and characterizing free nitrogen fixing bacteria
      (FNFB) of the genus Azotobacter, soil samples were collected randomly from
      different vegetable organic cultures with neutral pH in different zones of Boyaca
      Colombia. Isolations were done in selective free nitrogen Ashby-Sucrose agar
      obtaining a recovery of 40%. Twenty four isolates were evaluated for colony and
      cellular morphology, pigment production and metabolic activities. Molecular
      characterization was carried out using amplified ribosomal DNA restriction
      analysis (ARDRA). After digestion of 16S rDNA Y1-Y3 PCR products (1487pb) with
      AluI, HpaII and RsaI endonucleases, a polymorphism of 16% was obtained. Cluster
      analysis showed three main groups based on DNA fingerprints. Comparison between
      ribotypes generated by isolates and in silico restriction of 16S rDNA partial
      sequences with same restriction enzymes was done with Gen Workbench v.2.2.4
      software. Nevertheless, Y1-Y2 PCR products were analysed using BLASTn. Isolate
      C5T from tomato (Lycopersicon esculentum) grown soils presented the same in
      silico restriction patterns with A. chroococcum (AY353708) and 99% of similarity
      with the same sequence. Isolate C5CO from cauliflower (Brassica oleracea var.
      botrytis) grown soils showed black pigmentation in Ashby-Benzoate agar and high
      similarity (91%) with A. nigricans (AB175651) sequence. In this work we
      demonstrated the utility of molecular techniques and bioinformatics tools as a
      support to conventional techniques in characterization of the genus Azotobacter
      from vegetable-grown soils. 

PMID- 24031701
TI  - Microbial activity, arbuscular mycorrhizal fungi and inoculation of woody plants
      in lead contaminated soil.
AB  - The goals of this study were to evaluate the microbial activity, arbuscular
      mycorrhizal fungi and inoculation of woody plants (Caesalpinia ferrea, Mimosa
      tenuiflora and Erythrina velutina) in lead contaminated soil from the semi-arid
      region of northeastern of Brazil (Belo Jardim, Pernambuco). Dilutions were
      prepared by adding lead contaminated soil (270 mg Kg(-1)) to uncontaminated soil
      (37 mg Pb Kg soil(-1)) in the proportions of 7.5%, 15%, and 30% (v:v). The
      increase of lead contamination in the soil negatively influenced the amount of
      carbon in the microbial biomass of the samples from both the dry and rainy
      seasons and the metabolic quotient only differed between the collection seasons
      in the 30% contaminated soil. The average value of the acid phosphatase activity
      in the dry season was 2.3 times higher than observed during the rainy season.
      There was no significant difference in the number of glomerospores observed
      between soils and periods studied. The most probable number of infective
      propagules was reduced for both seasons due to the excess lead in soil. The
      mycorrhizal colonization rate was reduced for the three plant species assayed.
      The inoculation with arbuscular mycorrhizal fungi benefited the growth of
      Erythrina velutina in lead contaminated soil. 

PMID- 24031702
TI  - Partial characterization of cold active amylases and proteases of Streptomyces
      sp. from Antarctica.
AB  - The aim of this study was to isolate novel enzyme-producing bacteria from
      vegetation samples from East Antarctica and also to characterize them genetically
      and biochemically in order to establish their phylogeny. The ability to grow at
      low temperature and to produce amylases and proteases cold-active was also
      tested. The results of the 16S rRNA gene sequence analysis showed that the 4 Alga
      rRNA was 100% identical to the sequences of Streptomyces sp. rRNA from Norway and
      from the Solomon Islands. The Streptomyces grew well in submerged system at 20
      degrees C, cells multiplication up to stationary phase being drastically
      increased after 120 h of submerged cultivation. The beta-amylase production
      reached a maximum peak after seven days, while alpha-amylase and proteases were
      performing biosynthesis after nine days of submerged cultivation at 20 degrees C.
      Newly Streptomyces were able to produce amylase and proteases in a cold
      environment. The ability to adapt to low temperature of these enzymes could make
      them valuable ingredients for detergents, the food industry and bioremediation
      processes which require low temperatures. 

PMID- 24031703
TI  - Specific plant induced biofilm formation in Methylobacterium species.
AB  - Two endophytic strains of Methylobacterium spp. were used to evaluate biofilm
      formation on sugarcane roots and on inert wooden sticks. Results show that
      biofilm formation is variable and that plant surface and possibly root exudates
      have a role in Methylobacterium spp. host recognition, biofilm formation and
      successful colonization as endophytes. 

PMID- 24031704
TI  - Distribution of Vibrio alginolyticus-like species in Shenzhen coastal waters,
      China.
AB  - We investigated the distribution of vibrios in Shenzhen coastal waters in order
      to obtain valuable information for the aquaculture industry and a health warning
      system. Quantities of vibrios from surface waters ranged from 0 to 4.40*10(4)
      CFUs mL(-1) in April (spring), while from 0 to 2.57*10(3) CFUs mL(-1) in
      September (autumn); the abundance of V. alginolyticus-like species from surface
      water ranged from 0 to 6.72*10(3) CFUs mL(-1) in April (spring) and from 0 to
      1.28*10(3) CFUs mL(-1) in September (autumn); higher counts were observed in
      spring. The V. alginolyticus-like species was dominant in Shenzhen coastal
      waters, with the highest abundance in the clean region (stations YMK001 and
      GDN064) in April, suggesting that Vibrio spp. were naturally occurring bacteria
      in marine environments. The correlation between the abundance of vibrios
      (including V. alginolyticus-like species) and environmental factors varied in
      different regions and different seasons. There were no vibrios detected when the
      salinity was less than 11.150/00 in the Zhujiang River estuary, which indicated
      that salinity played a key role in the distribution of vibrios and V.
      alginolyticus-like species. 

PMID- 24031705
TI  - Bacterioplankton features and its relations with doc characteristics and other
      limnological variables in Parana river floodplain environments (PR/MS-Brazil).
AB  - Since the introduction of the Microbial Loop concept, many studies aimed to
      explain the role of bacterioplankton and dissolved organic carbon (DOC) in
      aquatic ecosystems. Parana River floodplain system is a very complex environment
      where these subjects were little explored. The aim of this work was to
      characterize bacterial community in terms of density, biomass and biovolume in
      some water bodies of this floodplain and to verify its temporal variation and its
      relation with some limnological variables, including some indicators of DOC
      quality, obtained through Ultraviolet-visible (UV-VIS) and fluorescence
      spectroscopic analysis. Bacterial density, biomass and biovolume are similar to
      those from other freshwater environments and both density and biomass were higher
      in the period with less rain. The limnological and spectroscopic features that
      showed any relation with bacterioplankton were the concentrations of N-NH4 and P
      PO4, water transparency, and some indicators of DOC quality and origin. The
      analysis of these relations showed a possible competition between
      bacterioplankton and phytoplankton for inorganic nutrients and that the DOC used
      by bacterioplankton is labile and probably from aquatic macrophytes. 

PMID- 24031706
TI  - Cellulase and xylanase activity during the decomposition of three aquatic
      macrophytes in a tropical oxbow lagoon.
AB  - Due to the connection between enzymatic activity and degradation of different
      fractions of organic matter, enzyme assays can be used to estimate degradation
      rates of particulate and dissolved organic carbon in freshwater systems. The aim
      of this study was to quantify and model the enzymatic degradation involving the
      decomposition of macrophytes, describing temporal activity of cellulases (EC
      3.2.1.4 and EC 3.2.1.91) and xylanase (EC 3.2.1.8) during in situ decomposition
      of three aquatic macrophytes (Salvinia sp., Eichhornia azurea and Cyperus
      giganteus) on the surface and water-sediment interface (w-s interface) of an
      oxbow lagoon (Oleo lagoon) within a natural Brazilian Savanna Reserve. Overall,
      the enzymatic degradation of aquatic macrophytes in Oleo lagoon occurred during
      the whole year and was initiated together with leaching. Xylanase production was
      ca. 5 times higher than cellulase values due to easy access to this compound by
      cellulolytic microorganisms. Enzymatic production and detritus mass decay were
      similar on the surface and w-s interface. Salvinia sp. was the most recalcitrant
      detritus, with low mass decay and enzymatic activity. E. azurea and C. giganteus
      decomposition rates and enzymatic production were high and similar. Due to the
      physicochemical homogeneity observed in the Oleo lagoon, the differences between
      the decay rates of each species are mostly related with detritus chemical
      quality. 

PMID- 24031707
TI  - Triple inoculation with Bradyrhizobium, Glomus and Paenibacillus on cowpea (Vigna
      unguiculata [L.] walp.) development.
AB  - The use of microorganisms to improve the availability of nutrients to plants is
      of great importance to agriculture. This study aimed to evaluate the effect of
      triple inoculation of cowpea with arbuscular mycorrhizal fungi (AMF), plant
      growth-promoting bacteria (PGPB) and rhizobia to maximize biological nitrogen
      fixation (BNF) and promote plant growth. The experiment was conducted in a
      greenhouse using cowpea plants (Vigna unguiculata L. Walp cv. IPA 206). The
      treatments included inoculation with strains of Bradyrhizobium sp. (BR 3267 and
      EI - 6) individually and as a mixture, an absolute control (AC) and mineral
      nitrogen control (NC), all combined with the presence or absence of native AMF
      (Glomus etunicatum) and PGPB (Paenibacillus brasilensis - 24) in a 5x2x2
      factorial design. All treatments were replicated three times. Contrasts were
      performed to study the treatment of variables. Inoculation with Bradyrhizobium
      sp. (BR 3267 and EI - 6) and G. etunicatum favored nitrogen acquisition and
      phosphorus availability for the cowpea plants. Inoculation with P. brasilensis -
      24 increased colonization by Bradyrhizobium sp. and G. etunicatum and promoted
      cowpea growth, while the nitrogen from symbiosis was sufficient to supply the
      plants nutritional needs. 

PMID- 24031708
TI  - Antarctic marine bacterium Pseudoalteromonas sp. KNOUC808 as a source of cold
      adapted lactose hydrolyzing enzyme.
AB  - Psychrophilic bacteria, which grow on lactose as a carbon source, were isolated
      from Antarctic polar sea water. Among the psychrophilic bacteria isolated, strain
      KNOUC808 was able to grow on lactose at below 5 degrees C, and showed 0.867 unit
      of o-nitrophenyl beta-D-galactopyranoside(ONPG) hydrolyzing activity at 4 degrees
      C. The isolate was gram-negative, rod, aerobic, catalase positive and oxidase
      positive. Optimum growth was done at 20 degrees C, pH 6.8-7.2. The composition of
      major fatty acids in cell of KNOUC801 was C12:0 (5.48%), C12:0 3OH (9.21%), C16:0
      (41.83%), C17:0 omega8 (7.24%) and C18:1 omega7 (7.04%). All these results
      together suggest that it is affiliated with Pseudoalteromonas genus. The 16S rDNA
      sequence corroborate the phenotypic tests and the novel strain was designated as
      Pseudoalteromonas sp. KNOUC808. The optimum temperature and pH for lactose
      hydrolyzing enzyme was 20 degrees C and 7.8, respectively. The enzyme was stable
      at 4 degrees C for 7 days, but its activity decreased to about 50% of initial
      activity at 37 degrees C in 7 days. 

PMID- 24031709
TI  - The diversity, extracellular enzymatic activities and photoprotective compounds
      of yeasts isolated in Antarctica.
AB  - The diversity of yeasts collected from different sites in Antarctica (Admiralty
      Bay, King George Island and Port Foster Bay and Deception Island) and their
      ability to produce extracellular enzymes and mycosporines were studied. Samples
      were collected during the austral summer season, between November 2006 and
      January 2007, from the rhizosphere of Deschampsia antarctica, ornithogenic
      (penguin guano) soil, soil, marine and lake sediments, marine water and
      freshwater from lakes. A total of 89 isolates belonging to the following genera
      were recovered: Bensingtonia, Candida, Cryptococcus, Debaryomyces, Dioszegia,
      Exophiala, Filobasidium, Issatchenkia (Pichia), Kodamaea, Leucosporidium,
      Leucosporidiella, Metschnikowia, Nadsonia, Pichia, Rhodotorula, and
      Sporidiobolus, and the yeast-like fungi Aureobasidium, Leuconeurospora and
      Microglossum. Cryptococcus victoriae was the most frequently identified species.
      Several species isolated in our study have been previously reported to be
      Antarctic psychophilic yeasts, including Cr. antarcticus, Cr. victoriae,
      Dioszegia hungarica and Leucosporidium scottii. The cosmopolitan yeast species A.
      pullulans, C. zeylanoides, D. hansenii, I. orientalis, K. ohmeri, P.
      guilliermondii, Rh. mucilaginosa, and S. salmonicolor were also isolated. Five
      possible new species were identified. Sixty percent of the yeasts had at least
      one detectable extracellular enzymatic activity. Cryptococcus antarcticus, D.
      aurantiaca, D. crocea, D. hungarica, Dioszegia sp., E. xenobiotica, Rh.
      glaciales, Rh. laryngis, Microglossum sp. 1 and Microglossum sp. 2 produced
      mycosporines. Of the yeast isolates, 41.7% produced pigments and/or mycosporines
      and could be considered adapted to survive in Antarctica. Most of the yeasts had
      extracellular enzymatic activities at 4 degrees C and 20 degrees C, indicating
      that they could be metabolically active in the sampled substrates. 

PMID- 24031710
TI  - Comparative study of the pathogenicity of seabed isolates of Fusarium equiseti
      and the effect of the composition of the mineral salt medium and temperature on
      mycelial growth.
AB  - The pathogenicity of seven strains of Fusarium equiseti isolated from seabed soil
      was evaluated on different host plants showing pre and post emergence damage.
      Radial growth of 27 strains was measured on culture media previously adjusted to
      different osmotic potentials with either KCl or NaCl (-1.50 to -144.54 bars) at
      15 degrees , 25 degrees  and 35 degrees  C. Significant differences and
      interactive effects were observed in the response of mycelia to osmotic potential
      and temperature. 

PMID- 24031711
TI  - Kluyveromyces aestuarii, a potential environmental quality indicator yeast for
      mangroves in the State of Rio de Janeiro, Brazil.
AB  - Kluyveromyces aestuarii was found in sediments from 7 of 8 mangroves in Rio de
      Janeiro; and absent only at one site with heavy plastic bag pollution. Its
      presence suggests influence in other habitats from a mangrove and its absence in
      a mangrove suggests some non- fecal pollution or other habitat alteration. 

PMID- 24031712
TI  - A survey of the bacterial diversity in the cup filler of dental chair units.
AB  - Water from the cup filler of dental chair units (CFDC) was observed to contain
      sphingomonads, environmental mycobacteria and methylobacteria, among other minor
      bacteria. Some of the bacteria detected are recognized opportunistic pathogens.
      Some of these, tended to persist over time. 

PMID- 24031713
TI  - Rapid identification of Mycobacterium tuberculosis complex by a novel
      hybridization signal amplification method based on self-assembly of DNA
      streptavidin nanoparticles.
AB  - Rapid detection of Mycobacterium tuberculosis complex (MTBC) is a critical step
      in controlling tuberculosis (TB). In this study, we used IS6110 as the specific
      identification target to develop a novel hybridization signal amplification
      method (HSAM) for the rapid and direct detection of MTBC from clinical sputum
      specimens. This system consists of magnetic bead-linked capture probes for target
      isolation, dextran-based nanoparticles for amplifying the reporter molecule
      (biotinylated-FITC), and detection probes (2B-DNA) for binding the nanoparticles.
      Both the capture and detection probes were specific to the IS6110 target
      sequence. Our results determined that as few as 10 copies of the IS6110 sequence
      or 10 M. tuberculosis bacteria could be detected, indicating that the HSAM assay
      is as sensitive as conventional PCR, and the assay was specific enough to
      distinguish MTBC from nontuberculosis mycobacteria (NTM). A total of 176 clinical
      sputum specimens were collected for HSAM evaluation, and the results were
      compared to those from traditional culture and biochemical identification
      techniques. This assay had a sensitivity of 88.3%, a specificity of 91.8%, a
      positive predictive value of 93.8% and a negative predictive value of 84.8% for
      the detection of MTBC. This technique is highly sensitive and specific, is easy
      to perform, and does not require any sophisticated detection equipment; thus,
      this approach has great potential in clinical TB detection and diagnostic
      applications. 

PMID- 24031714
TI  - Synergistic growth effect among bacteria recovered from root canal infections.
AB  - The objective of this study was to determine the ecological relationships between
      bacterial species that colonize infected root canals. Root canal bacteria
      recovered from one patient with pulp canal necrosis were evaluated in vitro for
      synergistic and antagonistic activities determined by mono and co-culture growth
      kinetics and the production of bacteriocin-like substances using the double layer
      diffusion method. Peptostreptococcus prevotii triggered a significant increase of
      Fusobacterium nucleatum growth, while the former bacteria did not affect the
      growth of P. prevotii. The bacterial species did not produce antagonism activity
      against itself or against any of the other two species. Despite many studies have
      demonstrated the capability of root canal microorganisms to produce antagonistic
      substances, these in vitro experimental tests show the synergistic effect of P.
      prevotii on the growth of F. nucleatum. 

PMID- 24031715
TI  - In vitro antibacterial activity of some antihistaminics belonging to different
      groups against multi-drug resistant clinical isolates.
AB  - Antihistaminics are widely used for various indications during microbial
      infection. Hence, this paper investigates the antimicrobial activities of 10
      antihistaminics belonging to both old and new generations using multiresistant
      Gram-positive and Gram-negative clinical isolates. The bacteriostatic activity of
      antihistaminics was investigated by determining their MIC both by broth and agar
      dilution techniques against 29 bacterial strains. Azelastine, cyproheptadine,
      mequitazine and promethazine were the most active among the tested drugs.
      Diphenhydramine and cetirizine possessed weaker activity whereas doxylamine,
      fexofenadine and loratadine were inactive even at the highest tested
      concentration (1 mg/ml). The MIC of meclozine could not be determined as it
      precipitated with the used culture media. The MBC values of antihistaminics were
      almost identical to the corresponding MIC values. The bactericidal activity of
      antihistaminics was also studied by the viable count technique in sterile saline
      solution. Evident killing effects were exerted by mequitazine, meclozine,
      azelastine and cyproheptadine. Moreover, the dynamics of bactericidal activity of
      azelastine were studied by the viable count technique in nutrient broth. This
      activity was found to be concentration-dependant. This effect was reduced on
      increasing the inoculum size while it was increased on raising the pH. The post
      antimicrobial effect of 100 MUg/ml azelastine was also determined and reached up
      to 3.36 h. 

PMID- 24031716
TI  - Membrane permeability alteration of some bacterial clinical isolates by selected
      antihistaminics.
AB  - Several antihistaminics possess antibacterial activity against a broad spectrum
      of bacteria. However, the exact mechanism of such activity was unclear. Hence,
      the aim of this study is to investigate their mechanism of antibacterial activity
      especially their effect upon the permeability of the bacterial cytoplasmic
      membrane. The effects of azelastine, cetirizine, cyproheptadine and
      diphenhydramine were studied using Gram-positive and Gram-negative multiresistant
      clinical isolates. Leakage of 260 and 280 nm UV-absorbing materials was detected
      upon treatment with the tested antihistaminics; indicative of membrane
      alteration. Using an artificial membrane model, cholesterol-free negatively
      charged unilamellar liposomes, confirmed the effect of antihistaminics upon the
      membrane permeability both by showing an apparent membrane damage as observed
      microscopically and by detection of leakage of preloaded dye from the liposomes
      colorimatrically. Moreover, examination of the ultrastructure of cells treated
      with azelastine and cetirizine under the transmission electron microscope
      substantiated the detected abnormalities in the cell wall and membrane.
      Furthermore, the effect of pretreating certain isolates for both short and long
      periods with selected antihistaminics was followed by the viable count technique.
      Increased vulnerability towards further exposure to azelastine was observed in
      cells pretreated with azelastine for 2 days and those pretreated with azelastine
      or cetrizine for 30 days. 

PMID- 24031717
TI  - Antifungal activity of Piper diospyrifolium Kunth (Piperaceae) essential oil.
AB  - In vitro activity of the essential oil from Piper diospyrifolium leaves was
      tested using disk diffusion techniques. The antifungal assay showed significant
      potencial antifungal activity: the oil was effective against several clinical
      fungal strains. The majority compounds in the essential oil were identified as
      sesquiterpenoids by GC-MS and GC-FID techniques. 

PMID- 24031718
TI  - Antifungal activity of different neem leaf extracts and the nimonol against some
      important human pathogens.
AB  - This study was conducted to evaluate the effect of aqueous, ethanolic and ethyl
      acetate extracts from neem leaves on growth of some human pathogens (Aspergillus
      flavus, Aspergillus fumigatus, Aspergillus niger, Aspergillus terreus, Candida
      albicans and Microsporum gypseum) in vitro. Different concentrations (5, 10, 15
      and 20%) prepared from these extracts inhibited the growth of the test pathogens
      and the effect gradually increased with concentration. The 20% ethyl acetate
      extract gave the strongest inhibition compared with the activity obtained by the
      same concentration of the other extracts. High Performance Liquid Chromatography
      (HPLC) analysis of ethyl acetate extract showed the presence of a main component
      (nimonol) which was purified and chemically confirmed by Nuclear Magnetic
      Resonance (NMR) spectroscopic analysis. The 20% ethyl acetate extract lost a part
      of its antifungal effect after pooling out the nimonol and this loss in activity
      was variable on test pathogens. The purified nimonol as a separate compound did
      not show any antifungal activity when assayed against all the six fungal
      pathogens. 

PMID- 24031719
TI  - Characterization of a chitinase with antifungal activity from a native Serratia
      marcescens B4A.
AB  - Chitinases have the ability of chitin digestion that constitutes a main compound
      of the cell wall in many of the phytopathogens such as fungi. In the following
      investigation, a novel chitinase with antifungal activity was characterized from
      a native Serratia marcescens B4A. Partially purified enzyme had an apparent
      molecular mass of 54 kDa. It indicated an optimum activity in pH 5 at 45 degrees
      C. Enzyme was stable in 55 degrees C for 20 min and at a pH range of 3-9 for 90
      min at 25 degrees C. When the temperature was raised to 60 degrees C, it might
      affect the structure of enzymes lead to reduction of chitinase activity.
      Moreover, the Km and Vmax values for chitin were 8.3 mg/ml and 2.4 mmol/min,
      respectively. Additionally, the effect of some cations and chemical compounds
      were found to stimulate the chitinase activity. In addition, Iodoacetamide and
      Idoacetic acid did not inhibit enzyme activity, indicating that cysteine residues
      are not part of the catalytic site of chitinase. Finally, chitinase activity was
      further monitored by scanning electronic microscopy data in which progressive
      changes in chitin porosity appeared upon treatment with chitinase. This enzyme
      exhibited antifungal activity against Rhizoctonia solani, Bipolaris sp,
      Alternaria raphani, Alternaria brassicicola, revealing a potential application
      for the industry with potentially exploitable significance. Fungal chitin shows
      some special features, in particular with respect to chemical structure.
      Difference in chitinolytic ability must result from the subsite structure in the
      enzyme binding cleft. This implies that why the enzyme didn't have significant
      antifungal activity against other Fungi. 

PMID- 24031721
TI  - Occurrence of yeasts, pseudomonads and enteric bacteria in the oral cavity of
      patients undergoing head and neck radiotherapy.
AB  - The aim of this study was to evaluate the occurrence of yeasts, pseudomonads and
      enteric bacteria in the oral cavity of patients undergoing radiotherapy (RT) for
      treatment of head and neck cancer. Fifty patients receiving RT were examined
      before, during and 30 days after RT. Saliva, mucosa, and biofilm samples were
      collected and microorganisms were detected by culture and polymerase chain
      reaction (PCR). The most prevalent yeasts in patients submitted to RT were
      Candida albicans, C. tropicalis, C. krusei, C. glabrata and C. parapsilosis.
      Citrobacter, Enterobacter, Enterococcus, Klebsiella, Proteus, and Pseudomonas
      were the most frequently cultivated bacteria. Before RT, targeted bacteria were
      cultivated from 22.2% of edentulous patients and 16.6% of dentate patients; 30
      days after RT, these microorganisms were recovered from 77.8% edentulous and
      46.8% dentate patients. By PCR, these microorganisms were detected from all
      edentulous patients, 78.1% of dentate patients. The presence of Gram-negative
      enteric roads and fungi was particularly frequent in patients presenting
      mucositis level III or IV. Modifications in the oral environment due to RT
      treatment seem to facilitate the colonization of oral cavity by members of family
      Enterobacteriaceae, genera Enterococcus and Candida. 

PMID- 24031720
TI  - Typing Candida albicans oral isolates from healthy brazilian schoolchildren using
      multilocus enzyme electrophoresis reveals two highly polymorphic taxa.
AB  - The genetic diversity of C. albicans oral isolates from 75 healthy schoolchildren
      from eight schools located in different geographic areas of Piracicaba city, Sao
      Paulo state, Brazil, was established using isoenzymes marker (Multilocus Enzyme
      Electrophoresis - MLEE) and cluster analysis. Patterns of monoclonal and
      polyclonal oral colonization by C. albicans within and between groups of
      schoolchildren were identified. However, significant divergence between the
      observed and the expected genotypic frequencies (Hardy-Weinberg equilibrium test)
      was not detected in the geographically adjacent groups, suggesting the hypothesis
      that populations of healthy schoolchildren do not correspond to the selection
      factor (differential survival) of strains. Two highly polymorphic and distantly
      genetically related taxa (A and B) were identified within the total population of
      yeasts, each contained subgroups (A1, A2, A3, A4, B1 and B2) and clusters of
      moderately related strains (from I to X), suggesting the existence of strains
      restricted or not to certain groups of geographically limited, healthy students.
      However, the coexistence of identical strains in healthy schoolchildren from the
      same school (geographically related) reinforces the hypothesis of oral
      transmission, where the sources of propagation could be explored. Furthermore,
      this could also be used in current and retrospective analyses of C. albicans
      isolated from immunocompetent and immunocompromised people, in order to detect
      commensal or potentially pathogenic yeast groups, predominantly in candidiasis,
      and in the development of strategies to prevent transmission or human
      propagation. 

PMID- 24031722
TI  - Peptidoglycan from Staphylococcus aureus induces the overexpression of TRLs 1-8
      mRNA in corneal fibroblasts, but its lipoteichoic acid and muramyl dipeptide only
      induced the overexpression of TLR5 or TRL9.
AB  - Lipopolysaccharide induces TLR-1-8 mRNAs over-expression in corneal fibroblast.
      Analyzing if other TLR-ligands can do the same, we found that peptidoglycan does,
      but not muramyldipeptide, lipoteichoic acid and polyI:C. This suggests that the
      recognition of lipopolysaccharide and peptidoglycan is enough to alert these
      cells against microorganisms through the over-expression of the majority TLRs. 

PMID- 24031723
TI  - Nutritional requirement among Pseudomonas aeruginosa isolates recovered from
      respiratory clinical specimens at a tertiary hospital from South of Brazil.
AB  - We screened 349 isolates of P. aeruginosa from cystic fibrosis (CF+) and non
      cystic fibrosis (CF-) patients for the auxotrophy. Fourteen (4.0%) were
      auxotrophic and among them only one was recovered from CF-patient showing that
      this characteristic is strongly associated with cystic fibrosis. In total, a
      requirement for 5 different compounds (or combination) was verified and, of
      these, methionine was the most common single amino acid required. Only one
      auxotrophic isolate was no able to produce biofilm in vitro. 

PMID- 24031724
TI  - Antifungal activity of five species of Polygala.
AB  - Crude extracts and fractions of five species of Polygala - P. campestris, P.
      cyparissias, P. paniculata, P. pulchella and P. sabulosa - were investigated for
      their in vitro antifungal activity against opportunistic Candida species,
      Cryptococcus gattii and Sporothrix schenckii with bioautographic and
      microdilution assays. In the bioautographic assays, the major extracts were
      active against the fungi tested. In the minimal concentration inhibitory (MIC)
      assay, the hexane extract of P. paniculata and EtOAc fraction of P. sabulosa
      showed the best antifungal activity, with MIC values of 60 and 30 MUg/mL,
      respectively, against C. tropicalis, C. gattii and S. schenckii. The compounds
      isolated from P. sabulosa prenyloxycoumarin and 1,2,3,4,5,6-hexanehexol displayed
      antifungal activity against S. schenckii (with MICs of 125 MUg/mL and 250 MUg/mL,
      respectively) and C. gattii (both with MICs of 250 MUg/mL). Rutin and aurapten
      isolated from P. paniculata showed antifungal activity against C. gattii with MIC
      values of 60 and 250 MUg/mL, respectively. In the antifungal screening, few of
      the isolated compounds showed good antifungal inhibition. The compound alpha
      spinasterol showed broad activity against the species tested, while rutin had the
      best activity with the lowest MIC values for the microorganisms tested. These two
      compounds may be chemically modified by the introduction of a substitute group
      that would alter several physico-chemical properties of the molecule, such as
      hydrophobicity, electronic density and steric strain. 

PMID- 24031725
TI  - Extended-spectrum beta-lactamase-producing bacteria isolated from hematologic
      patients in Manaus, State of Amazonas, Brazil.
AB  - Antibiotic therapy in hematologic patients, often weak and susceptible to a wide
      range of infections, particularly nosocomial infections derived from long
      hospitalization periods, is a challenging issue. This paper presents ESBL
      producing strains isolated from such hematologic patients treated at the Amazon
      Hematology and Hemotherapy Foundation (HEMOAM) in the Brazilian Amazon Region to
      identify the ESBL genes carried by them as well as the susceptibility to 11
      antimicrobial agents using the E-test method. A total of 146 clinical samples
      were obtained from July 2007 to August 2008, when 17 gram-negative strains were
      isolated in our institution. The most frequent isolates confirmed by biochemical
      tests and 16S rRNA sequencing were E. coli (8/17), Serratia spp. (3/17) and
      B.cepacia (2/17). All gram-negative strains were tested for extended-spectrum
      beta-lactamases (ESBLs), where: (12/17) strains carried ESBL; among these, (8/12)
      isolates carried bla TEM, bla CTX-M, bla OXA , bla SHV genes, (1/12) bla TEM gene
      and (3/12) bla TEM, bla CTX-M, bla OXA genes. Antibiotic resistance was found in
      (15/17) of the isolates for tetracycline, (12/17) for ciprofloxacin, (1/17)
      resistance for cefoxitin and chloramphenicol, (1/17) for amikacin and (3/17)
      cefepime. This research showed the presence of gram-negative ESBL-producing
      bacteria infecting hematologic patients in HEMOAM. These strains carried the bla
      TEM, bla SHV, bla CTX-M and bla OXA genes and were resistant to different
      antibiotics used in the treatment. This finding was based on a period of 13
      months, during which clinical samples from specific populations were obtained.
      Therefore, caution is required when generalizing the results that must be based
      on posological orientations and new breakpoints for disk diffusion and
      microdilution published by CLSI 2010. 

PMID- 24031726
TI  - Response surface methodology of nitrilase production by recombinant Escherichia
      coli.
AB  - Growth and nitrilase production by recombinant Escherichia coli cells harbouring
      pET 21 (b) plasmid, for the expression of Pseudomonas putida nitrilase were
      improved using response surface methodology. Central composite design was used
      for obtaining ideal concentration of critical medium components which include
      fructose, tryptone, yeast extract and lactose. The optimal values for the
      concentration of fructose, tryptone, yeast extract and lactose were found to be
      1.13, 2.26, 3.25 and 0.9 % (w/v), respectively. Here, fructose served as carbon
      source for the growth while lactose was preferably used as inducer for the
      expression of foreign protein. Yeast extract in the medium was used as a growth
      promoter while tryptone was added as a major nitrogen source. Using this
      optimized medium, an experimental growth of 6.67 (OD at 600 nm) and nitrilase
      activity of 27.13 U/ml was achieved. This approach for medium development led to
      an enhancement of the growth and enzyme activity by 1.4 and 2.2 times,
      respectively, as compared to the un-optimized medium. 

PMID- 24031727
TI  - Medium composition influence on Biotin and Riboflavin production by newly
      isolated Candida sp.
AB  - Complex B vitamins as Biotin and Riboflavin are required by living organisms, not
      only for growth but also for metabolite production, and the feed market
      classifies them as growth promoters. Since Brazil will soon be one of the world's
      biggest animal protein producers, feed production is a large consumer of vitamins
      and micronutrients. The industry requires 10 mg riboflavin/0.2 mg biotin per
      kilogram of feed; a ratio of 40 ~ 50:1. Although few studies have been conducted
      specifically on riboflavin production using factorial design and surface response
      method as an optimization strategy, it is a common practice in biotechnology with
      many research reports available. However, there are no reports on the use of
      statistical design for biotin production. This study set out to evaluate medium
      composition influence on biotin and riboflavin production using a statistical
      design. There are no studies relating biotin and riboflavin production by Candida
      sp LEB 130. In this preliminary study to improve the simultaneous production of
      biotin and riboflavin, the maximum riboflavin/biotin ratio of 8.3 MUg/mL was
      achieved with medium component concentrations of: sucrose 30 g/L, KH2PO4 2 g/L,
      MgSO4 1 g/L and ZnSO4 0.5mL/L. 

PMID- 24031728
TI  - Lignin degradation, ligninolytic enzymes activities and exopolysaccharide
      production by Grifola frondosa strains cultivated on oak sawdust.
AB  - Fourteen strains of Grifola frondosa (Dicks.) S. F. Gray, originating from
      different regions (Asia, Europe and North America) were tested for lignin
      degradation, ligninolytic enzyme activities, protein accumulation and
      exopolysaccharide production during 55 days of cultivation on oak sawdust. Lignin
      degradation varied from 2.6 to7.1 % of dry weight of the oak sawdust substrate
      among tested strains. The loss of dry matter in all screened fungi varied between
      11.7 and 33.0%, and the amount of crude protein in the dry substrate varied
      between 0.94 to 2.55%. The strain, MBFBL 596, had the highest laccase activity
      (703.3 U/l), and the maximum peroxidase activity of 22.6 U/l was shown by the
      strain MBFBL 684. Several tested strains (MBFBL 21, 638 and 662) appeared to be
      good producers of exopolysaccharides (3.5, 3.5 and 3.2 mg/ml respectively). 

PMID- 24031729
TI  - Production and characterization of PHA from recombinant E. coli harbouring phaC1
      gene of indigenous Pseudomonas sp. LDC-5 using molasses.
AB  - Polyhydroxyalkanoates (PHA) are biodegradable and biocompatible green
      thermoplastics, synthesized by wide variety of bacteria as an intracellular
      carbon and energy storage intermediate. They are used as an alternative to
      nonrenewable petroleum derived plastics. The current interest in these
      biopolyesters is stimulated by the search for cost-effective capitalized
      production. This paper attempts to achieve maximized production rate from
      recombinant system using inexpensive substrate. Molasses from agro-industrial
      waste was used to produce PHA from recombinant E.coli in batch culture. PHA yield
      in molasses (3.06g/L +/- 0.05-75.5%) was higher than that of sucrose (2.5g/L +/-
      0.05 - 65.1%). Properties of the polymer produced from molasses and sucrose were
      analyzed by DSC, TGA, DTA, GC/MS, TLC and optical rotation studies. The findings
      suggested that molasses enhanced PHA production in recombinant E.coli. 

PMID- 24031730
TI  - Production of cellulose by Aspergillus niger under submerged and solid state
      fermentation using coir waste as a substrate.
AB  - Aspergillus niger was used for cellulase production in submerged (SmF) and solid
      state fermentation (SSF). The maximum production of cellulase was obtained after
      72 h of incubation in SSF and 96 h in Smf. The CMCase and FPase activities
      recorded in SSF were 8.89 and 3.56 U per g of dry mycelial bran (DBM),
      respectively. Where as in Smf the CMase & FPase activities were found to be 3.29
      and 2.3 U per ml culture broth, respectively. The productivity of extracellular
      cellulase in SSF was 14.6 fold higher than in SmF. The physical and nutritional
      parameters of fermentation like pH, temperature, substrate, carbon and nitrogen
      sources were optimized. The optimal conditions for maximum biosynthesis of
      cellulase by A. niger were shown to be at pH 6, temperature 30  degrees C. The
      additives like lactose, peptone and coir waste as substrate increased the
      productivity both in SmF and SSF. The moisture ratio of 1:2 (w/v) was observed
      for optimum production of cellulase in SSF. 

PMID- 24031731
TI  - Growth and biopigment accumulation of cyanobacterium Spirulina platensis at
      different light intensities and temperature.
AB  - In order to find out optimum culture condition for algal growth, the effect of
      light irradiance and temperature on growth rate, biomass composition and pigment
      production of Spirulina platensis were studied in axenic batch cultures. Growth
      kinetics of cultures showed a wide range of temperature tolerance from 20 
      degrees C to 40  degrees C. Maximum growth rate, cell production with maximum
      accumulation of chlorophyll and phycobilliproteins were found at temperature 35 
      degrees C and 2,000 lux light intensity. But with further increase in temperature
      and light intensity, reduction in growth rate was observed. Carotenoid content
      was found maximum at 3,500 lux. Improvement in the carotenoid content with
      increase in light intensity is an adaptive mechanism of cyanobacterium
      S.platensis for photoprotection, could be a good basis for the exploitation of
      microalgae as a source of biopigments. 

PMID- 24031732
TI  - Thermostable saccharogenic amylase produced under submerged fermentation by
      filamentous fungus Penicillium purpurogenum.
AB  - The effect of several nutritional and environmental parameters on Penicillium
      purpurogenum growth and sacharogenic amylase production was analyzed. High enzyme
      levels (68.2 U mg(-1)) were obtained with Khanna medium at initial pH 6.0,
      incubated at 30 degrees C for 144 hours. The optimum pH and temperature
      activities were 5.0 and 65 degrees C, respectively. The enzyme presented a half
      life (t50) of 60 min, at 65 degrees C. Only glucose was detected after 24 hours
      of reaction using soluble starch as substrate. 

PMID- 24031733
TI  - Evaluation of sorghum straw hemicellulosic hydrolysate for biotechnological
      production of xylitol by Candida guilliermondii.
AB  - A preliminary study on xylitol production by Candida guilliermondii in sorghum
      straw hemicellulosic hydrolysate was performed. Hydrolysate had high xylose
      content and inhibitors concentrations did not exceed the commonly found values in
      other hemicellulosic hydrolysates. The highest xylitol yield (0.44 g/g) and
      productivity (0.19 g/Lh) were verified after 72 hours. 

PMID- 24031734
TI  - Ultrastructural study of the mycelial phase of clinical isolates of Sporothrix
      schenckii obtained from feline, canine and human cases of sporotrichosis.
AB  - Using transmission electron microscopy, we studied the presence of melanin and
      cell wall thickness of clinical isolates of Sporothrix schenckii obtained from
      cats, dogs and humans as compared to reference strains. We detected differences
      regarding presence of the melanin among the clinical isolates of S. schenckii and
      a correlation between presence of melanin and cell wall thickness. 

PMID- 24031735
TI  - Fungal microbiota from ocular conjuctiva of clinically healthy horses belonging
      to the military police cavalry of alagoas.
AB  - Normal fungal conjunctiva microbiota of horses remains stable in healthy animals,
      free from ocular and/or systemic diseases which may, eventually, cause ocular
      alterations. The knowledge of the fungal microbiota is of great importance due to
      the reduced number of studies reported in the literature and also to the large
      occurrence of ocular alterations, mainly keratomycosis, in these animals. The aim
      of this study was to isolate and to identify the fungi present in the ocular
      conjunctiva of healthy horses belonging to the Military Police Cavalry of
      Alagoas. Samples from both conjunctival sacks from 50 horses were taken using a
      sterile swab and submitted to fungal cultures. These samples were seeded by
      radial spreading of the swabs on the Sabouraud agar surface with chloramphenicol,
      at a concentration of 50mg/L, in Petri dishes. Next, dishes were incubated at
      room temperature (+/- 28 degrees C) for 15 days. Horses conjunctival fungal
      microbiota was found to be composed by Aspergillus spp. (62%), Microsporum
      gypseum (6%), Penicillium spp. (6%), Curvularia spp. (5%), Candida spp. (3%),
      Fusarium spp. (3%), Acremonium spp. (2%), Bipolaris sp. (1%), Cladosporium sp.
      (1%), Chrysosporium sp. (1%), Rhodotorula sp. (1%), Aureobasidium sp. (1%) and
      Scopulariopsis sp. (1%). There is a wide variety of yeast-like and filamentous
      fungi colonizing the clinically healthy horses' ocular conjunctiva, out of which
      Aspergillus sp. is predominant. Although this was a straightforward study and
      have not recorded any ocular lesions that suggest fungi infections, these fungi
      might eventually be involved in this type of ocular pathology for the studied
      species. 

PMID- 24031736
TI  - Retrospective study on Porcine circovirus-2 by nested pcr and real time pcr in
      archived tissues from 1978 in brazil.
AB  - Porcine circovirus-2 (PCV-2) infection is currently considered an important
      disease of swine. The pathogenic agent was first described in Brazil in 2000.
      This study detected the PCV-2 DNA in four Brazilian pig tissues collected between
      1978 and 1979. This observation is the oldest description of this virus in
      Brazil. 

PMID- 24031737
TI  - Stable expression and potential use of west nile virus envelope glycoproteins
      preM/E as antigen in diagnostic tests.
AB  - West Nile virus (WNV) envelope glycoproteins preM/E were stably expressed in baby
      hamster kidney cells and tested as antigen in a fluorescent antibody assay for
      WNV antibodies. Sera from horses, mice and chicken immunized with an inactivated
      WNV vaccine and, less consistently, sera from horses acutely infected with WNV,
      reacted specifically with viral antigens present in preM/E-expressing cells. 

PMID- 24031738
TI  - Transcription of interferon stimulated genes in response to Porcine rubulavirus
      infection in vitro.
AB  - Porcine rubulavirus (PoRV) is an emerging virus causing meningo-encephalitis and
      reproductive failures in pigs. Little is known about the pathogenesis and immune
      evasion of this virus; therefore research on the mechanisms underlying tissue
      damage during infection is essential. To explore these mechanisms, the effect of
      PoRV on the transcription of interferon (IFN) pathway members was analyzed in
      vitro by semi-quantitative RT-PCR. Ten TCID50 of PoRV stimulated transcription of
      IFNalpha, IFNbeta, STAT1, STAT2, p48 and OAS genes in neuroblastoma cells,
      whereas infection with 100 TCID50 did not stimulate transcription levels more
      than non-infected cells. When the cells were primed with IFNalpha, infection with
      1 TCDI50 of PoRV sufficed to stimulate the transcription of the same genes, but
      10 and 100 TCID50 did not modify the transcription level of those genes as
      compared with non-infected and primed controls. MxA gene transcription was
      observed only when the cells were primed with IFNalpha and stimulated with 10
      TCID50, whereas 100 TCID50 of PoRV did not modify the MxA transcription level as
      compared to non-infected and primed cells. Our results show that PoRV replication
      at low titers stimulates the expression of IFN-responsive genes in neuroblastoma
      cells, and suggest that replication of PoRV at higher titers inhibits the
      transcription of several members of the IFN pathway. These findings may
      contribute to the understanding of the pathogenesis of PoRV. 

PMID- 24031739
TI  - First report of White spot syndrome virus in farmed and wild penaeid shrimp from
      lagoa dos patos estuary, southern brazil.
AB  - In this study, we detected White spot syndrome virus (WSSV) in wild
      Farfantepenaeus paulensis collected in the Lagoa dos Patos estuary and cultivated
      Litopenaeus vannamei. This is the first report of WSSV in F. paulensis from Lagoa
      dos Patos and farmed L. vannamei shrimps in Rio Grande do Sul. 

PMID- 24031740
TI  - Expression of mouse beta defensin 2 in escherichia coli and its broad-spectrum
      antimicrobial activity.
AB  - Mature mouse beta defensin 2 (mBD2) is a small cationic peptide with
      antimicrobial activity. Here we established a prokaryotic expression vector
      containing the cDNA of mature mBD2 fused with thioredoxin (TrxA), pET32a-mBD2.
      The vector was transformed into Escherichia Coli (E. coli) Rosseta-gami (2) for
      expression fusion protein. Under the optimization of fermentation parameters:
      induce with 0.6 mM isopropylthiogalactoside (IPTG) at 34 degrees C in 2*YT medium
      and harvest at 6 h postinduction, fusion protein TrxA-mBD2 was high expressed in
      the soluble fraction (>95%). After cleaved fusion protein by enterokinase,
      soluble mature mBD2 was achieved 6 mg/L with a volumetric productivity. Purified
      recombinant mBD2 demonstrated clear broad-spectrum antimicrobial activity for
      fungi, bacteria and virus. The MIC of antibacterial activity of against
      Staphylococcus aureus was 50 MUg/ml. The MIC of against Candida albicans (C.
      albicans) and Cryptococcus neoformans (C. neoformans) was 12.5MUg/ml and
      25MUg/ml, respectively. Also, the antimicrobial activity of mBD2 was effected by
      NaCl concentration. Additionally, mBD2 showed antiviral activity against
      influenza A virus (IAV), the protective rate for Madin-Darby canine kidney cells
      (MDCK) was 93.86% at the mBD2 concentration of 100 MUg/ml. These works might
      provide a foundation for the following research on the mBD2 as therapeutic agent
      for medical microbes. 

PMID- 24031741
TI  - Identification and biological activity of potential probiotic bacterium isolated
      from the stomach mucus of breast-fed lamb.
AB  - The lactic acid bacterium E isolated from the stomach mucus of breast-fed lamb
      was identified by sequencing of 16S rDNA fragment and species-specific PCR as
      Lactobacillus reuteri. Its potential antimicrobial activity and ability to
      modulate immune system in vitro and in vivo was determined. The growth inhibition
      of potential pathogens decreased from Staphylococcus aureus, Pseudomonas
      aeruginosa, Salmonella enterica ser. Minnesota to Escherichia coli. The lowest
      inhibition activity was observed in the case of Candida albicans. The ability of
      L. reuteri E to modulate biological activities of human and mouse mononuclear
      cells was estimated in vitro and in vivo, respectively. The production of IL
      1beta by monocytes in vitro was significantly induced by L. reuteri E (relative
      activity 2.47). The ability to modulate biological activities of mononuclear
      cells by living L. reuteri E cells in vitro in comparison to disintegrated L.
      reuteri E cells in vivo differed. For example lysozyme activity in vitro was
      inhibited while in vivo was stimulated (relative activities 0.30 and 1.83,
      respectively). The peroxidase activity in vitro was stimulated while in vivo was
      inhibited (relative activities 1.53 and 0.17, respectively). Obtained results
      indicate that L. reuteri E is potential candidate to be used in probiotic
      preparations for animals and/or human. 

PMID- 24031742
TI  - Growth response of Pinus densiflora seedlings inoculated with three indigenous
      ectomycorrhizal fungi in combination.
AB  - Pinus densiflora seedlings were inoculated with three indigenous ectomycorrhizal
      fungi (Cenococcum geophilum, Rhizopogon roseolus and Russula densifolia) in
      single-, two-, and three-species treatments. After 8 months, the colonization
      rates of each ectomycorrhizal species, seedling growth and the nutrition were
      assessed in each treatment. P. densiflora seedlings inoculated with different ECM
      species composition showed an increase in height and basal diameter and improved
      seedling root and shoot nutrition concentrations compared to control treatment.
      Generally, combined inoculation had a more positive influence on the seedlings
      than the single inoculation. The three-species inoculation presented the highest
      growth and basal diameter and concentration of most nutrients except potassium.
      In conclusion, the results provided strong evidence for benefits of combined
      inoculation with the indigenous ectomycorrhizal fungi on P. densiflora seedlings
      under controlled conditions. 

PMID- 24031743
TI  - Characterization of outbreak hepatitis a isolates in five Tunisian childcare
      centers.
AB  - In the present study, epidemiological survey and molecular characterization of
      hepatitis A virus during an outbreak in five Tunisian childcare centers in El
      Mahres during October and November 2006 were carried out. Five well-water and
      five drinking water samples were included in the present study. Serological
      investigation and molecular characterization were carried out. All patients were
      IgM seropositive and the viral genome was detected in all clinical and well-water
      samples whereas it was not detected in drinking water from the five childcare
      centers. Sequence analysis showed that all Tunisian strains belong to sub
      genotype IA. The genetic profile of the VP1/2A junction showed that the outbreak
      isolates underwent an amino acid substitution which was absent in virus's strains
      detected previously in Tunisia. Further studies need to be conducted to evaluate
      the emergence of the virus's strains in clinical and water samples and more
      epidemiological data need to be collected about the risk factors which may
      contribute to acute hepatitis. 

PMID- 24031744
TI  - Expression of HMGB1 and HMGN2 in gingival tissues, GCF and PICF of periodontitis
      patients and peri-implantitis.
AB  - High mobility group chromosomal protein B1 (HMGB1) and N2 (HMGN2), two members of
      High mobility group (HMG) family, play important role in inflammation. The
      purposes of this study were to investigate the expression of HMGB1 and HMGN2 in
      periodontistis. The expression of HMGB1 and HMGN2 mRNA in gingival tissues and
      gingival crevicular fluid (GCF) in chronic periodontitis (CP), generalized
      aggressive periodontitis (G-AgP) patients and healthy subjects was detected by
      real-time PCR. The protein level of HMGB1 and HMGN2 in peri-implant crevicular
      fluid (PICF), peri-implant crevicular fluid of peri-implantitis (PI-PICF) and
      normal patients was determined by Western blotting. Furthermore, IL-1beta, IL-6,
      IL-8, TNF-alpha and HMGB1 levels in GCF, PI-PICF and healthy -PICF samples from
      different groups were determined by ELISA. HMGN2 expression was increased in
      inflamed gingival tissues and GCF from CP and G-ApG groups compared to control
      group. HMGB1 expression was the highest in the gingival tissues and GCF from CP
      patients and was accompanied by increased concentrations of IL-1beta, IL-6, IL-8
      proinflammaory cytokines. To our knowledge, this is the first study reporting
      that the expression of HMGB1 and HMGN2 was increased in the gingival tissues and
      GCF in CP and G-AgP and the PICF in PICF. Our data suggest that HMGB1 may be a
      potential target for the therapy of periodontitis and PI. 

PMID- 24031745
TI  - Evaluation of INNO-LiPA mycobacteria v2 assay for identification of rapidly
      growing mycobacteria.
AB  - A total of 54 rapidly growing mycobacteria (RGM) isolated from patients attended
      in the two hospitals of Cadiz Bay (Spain) were selected during a seven-year
      period (2000-2006) in order to evaluate the INNO-LiPA Mycobacteria v2 assay for
      mycobacterial identification, based on the reverse hybridization principle. The
      strains were cultured in Lowenstein-Jensen and Middlebrook 7H9 media and
      identified to the species level by sequencing of the 16S rRNA, PCR-restriction
      enzyme analysis of the hsp65 gene, conventional tests and INNO-LiPA Mycobacteria
      v2 assay. By the molecular methods we identified a total of 12 different species:
      23 Mycobacterium fortuitum, 11 M. chelonae, 10 M. abscessus, 2 M. senegalense, 1
      M. alvei, 1 M. brumae, 1 M. mageritense, 1 M. mucogenicum, 1 M. neoaurum, 1 M.
      peregrinum, 1 M. septicum and 1 M. smegmatis. Fifty two strains (96.3%) were
      correctly identified by conventional techniques and 47 strains (87.0%) by INNO
      LiPA Mycobacteria v2 assay. We find INNO-LiPA Mycobacteria v2 assay simple to
      perform but it provides few advantages in comparison with conventional methods
      and sometimes needs complementary tests to identify Mycobacterium fortuitum
      complex, M. chelonae complex and specific species due to the great heterogeneity
      in the RGM group. 

PMID- 24031746
TI  - Bioconversion of ginsenoside rb1 into compound k by Leuconostoc citreum LH1
      isolated from kimchi.
AB  - About 40 different types of ginsenoside (ginseng saponin), a major
      pharmacological component of ginseng, have been identified along with their
      physiological activities. Among these, compound K has been reported to prevent
      the development of and the metastasis of cancer by blocking the formation of
      tumors and suppressing the invasion of cancerous cells. In this study,
      ginsenoside Rb1 was converted into compound K via interaction with the enzyme
      secreted by beta-glucosidase active bacteria, Leuconostoc citreum LH1, extracted
      from kimchi. The optimum time for the conversion of Rb1 to compound K was about
      72 hrs at a constant pH of 6.0 and an optimum temperature of about 30 degrees C.
      Under optimal conditions, ginsenoside Rb1 was decomposed and converted into
      compound K by 72 hrs post-reaction (99%). Both TLC and HPLC were used to analyze
      the enzymatic reaction. Ginsenoside Rb1 was consecutively converted to
      ginsenoside Rd, F2, and compound K via the hydrolyses of 20-C beta-(1 -> 6)
      glucoside, 3-C beta-(1 -> 2)-glucoside, and 3-C beta-glucose of ginsenoside Rb1. 

PMID- 24031747
TI  - Effect of ingestion of soy yogurt on intestinal parameters of rats fed on a beef
      based animal diet.
AB  - The aim of this study was to investigate whether the ingestion of soy yogurt
      fermented with Enterococcus faecium CRL 183 would modify the intestinal count of
      enterococci, fecal pH and ammonia content in rats fed on a diet containing red
      meat. The rats were placed in 4 groups: for 60 days, group I was given a standard
      casein-based rodent feed and groups II-IV, the beef-based feed. From day 30,
      groups III-IV also received the following products: III) soy yogurt; IV)
      suspension of E. faecium CRL 183. At the start and on days 30 and 60, feces were
      collected for the determination of pH, ammonia content, count of enterococci and
      identification of their species. On day 60, rats were sacrificed and their colons
      also removed for count of enterococci and identification of their species. Rats
      that ingested soy yogurt showed no significant change (P<0.05) in fecal counts of
      Enterococcus spp., but, this rat group showed a higher count of E. faecium than
      rats that ingested suspension of E. faecium CRL 183. The ingestion of soy yogurt
      and E. faecium culture caused a significant rise (P < 0.05) in fecal pH and
      ammonia content. Our results suggest that consumption of soy yogurt fermented
      with E. faecium CRL 183 and L. helveticus subsp. jugurti could change the species
      of Enterococcus spp. present in the feces and colon of rats fed on a beef-based
      diet. However, the fermented soy product and the pure culture of E. faecium CRL
      183 also induced undesirable effects such as the increase of fecal pH and ammonia
      content in the feces of rats fed on a beef-based diet. 

PMID- 24031749
TI  - Evaluation of the in vitro antimicrobial activity of an ethanol extract of
      Brazilian classified propolis on strains of Staphylococcus aureus.
AB  - Staphylococcus aureus (S. aureus) is one of the most frequent causes of hospital
      acquired infections. With the increase in multiple drug resistant strains,
      natural products such as propolis are a stratagem for new product discovery. The
      aims of this study were: to determine the in vitro antimicrobial activity of an
      ethanol extract of propolis; to define the MIC50 and MIC90 (Minimal Inhibitory
      Concentration - MIC) against 210 strains of S. aureus; to characterize a crude
      sample of propolis and the respective ethanol extract as to the presence of
      predetermined chemical markers. The agar dilution method was used to define the
      MIC and the high performance liquid chromatography (HPLC) method was used to
      characterize the samples of propolis. MIC results ranged from 710 to 2,850 ug/mL.
      The MIC50 and MIC90 for the 210 strains as well as the individual analysis of
      American Type Culture Collection (ATCC) strains of Methicillin-susceptible
      Staphylococcus aureus (MSSA) and Methicillin-resistant Staphylococcus aureus
      (MRSA) were both 1,420 ug/mL. Based on the chromatographic analysis of the crude
      sample and ethanol extracted propolis, it was concluded that propolis was a
      mixture of the BRP (SP/MG) and BRP (PR) types. The results obtained confirm an
      antimicrobial activity in relation to the strains of the S. aureus tested. 

PMID- 24031748
TI  - Mutacins of Streptococcus mutans.
AB  - The colonization and accumulation of Streptococcus mutans are influenced by
      various factors in the oral cavity, such as nutrition and hygiene conditions of
      the host, salivary components, cleaning power and salivary flow and
      characteristics related with microbial virulence factors. Among these virulence
      factors, the ability to synthesize glucan of adhesion, glucan-binding proteins,
      lactic acid and bacteriocins could modify the infection process and pathogenesis
      of this species in the dental biofilm. This review will describe the role of
      mutacins in transmission, colonization, and/or establishment of S. mutans, the
      major etiological agent of human dental caries. In addition, we will describe the
      method for detecting the production of these inhibitory substances in vitro
      (mutacin typing), classification and diversity of mutacins and the regulatory
      mechanisms related to its synthesis. 

PMID- 24031750
TI  - Comparison of teicoplanin disk diffusion and broth microdilution methods against
      clinical isolates of Staphylococcus aureus and S. epidermidis.
AB  - The CLSI M100-S19 document has recommended the disuse of vancomycin disks for
      staphylococci and informed that studies on the action of teicoplanin in disk
      diffusion testing should be performed. We describe the comparison of two methods,
      disk diffusion and broth microdilution, for determining teicoplanin
      susceptibility in clinical isolates of staphylococci. Overall results showed an
      aggregation rate of 96.8%; Staphylococcus aureus showed total agreement while S.
      epidermidis showed 93.8% of agreement. According to these local results, disk
      diffusion can still be employed to teicoplanin susceptibility determination for
      staphylococci in our institution. 

PMID- 24031751
TI  - Evaluation of antifungal activity in essential oil of the Syzygium aromaticum
      (L.) by extraction, purification and analysis of its main component eugenol.
AB  - Antifungal properties of some essential oils have been well documented. Clove oil
      is reported to have strong antifungal activity against many fungal species. In
      this study we have evaluated antifungal potential of essential oil of Syzygium
      aromaticum (L.) against some common fungal pathogens of plants and animals
      namely, Fusarium moniliforme NCIM 1100, Fusarium oxysporum MTCC 284, Aspergillus
      sp., Mucor sp., Trichophyton rubrum and Microsporum gypseum. All fungal species
      were found to be inhibited by the oil when tested through agar well diffusion
      method. Minimum inhibitory concentration (MIC) was determined for all the
      species. Column chromatography was performed to separate the eugenol rich
      fraction from clove oil. Out of seven fractions maximum activity was obtained in
      column fraction II. TLC and HPLC data confirmed presence of considerable Eugenol
      in fraction II and clove oil. Microscopic study on effect of clove oil and column
      fraction II on spores of Mucor sp. and M. gypseum showed distortion and shrinkage
      while it was absent in other column fractions. So it can be concluded that the
      antifungal action of clove oil is due to its high eugenol content. 

PMID- 24031752
TI  - Multiple drug resistance patterns in various phylogenetic groups of uropathogenic
      E.coli isolated from Faisalabad region of Pakistan.
AB  - The objective of this work was the phylogenetic characterization of local
      clinical isolates of uropathogenic E. coli with respect to drug resistance. A
      total of 59 uropathogenic E. coli responsible for community acquired urinary
      tract infections were included in this study. A triplex PCR was employed to
      segregate each isolate into four different phylogenetic groups (A, B1, B2 and D).
      Drug resistance was evaluated by disc diffusion method. The drugs used were
      ampicillin, aztreonam, cefixime, cefoperazone, ceftriaxone, cephradine among beta
      lactam group; amikacin, gentamicin, and streptomycin among aminoglycosides;
      nalidixic acid and ciprofloxacin from quinolones; trimethoprim-sulfomethoxazole,
      and tetracycline. Among 59 uropathogenic E. coli isolates majority belonged to
      phylogenetic group B2 (50%) where as 19% each belonged to groups A and B1, and
      12% to group D. All the isolates were multiple drug resistant (MDR). Most
      effective drugs against Group A, B1, and B2 were gentamicin, amikacin and
      cefixime; ceftriaxone and quinolones; and ceftriaxone and amikacin, respectively.
      Group D isolates were found to be highly resistant to all drugs. Our results have
      shown emergence of MDR isolates among uropathogenic E. coli with dominance of
      phylogenetic group B2. However, it was found that group D isolates were though
      less frequent, more drug resistant as compared with group B2. Groups A and B1
      were relatively uncommon. Amikacin, ceftriaxone and gentamicin were the most
      effective drugs in general. 

PMID- 24031753
TI  - Detection of extended spectrum beta lactamases, ampc beta lactamases and
      metallobetalactamases in clinical isolates of ceftazidime resistant Pseudomonas
      Aeruginosa.
AB  - We studied the prevalence of ceftazidime resistance in Pseudomonas aeruginosa and
      the rates of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase (AmpC)
      and metallo-beta-lactamase (MBL) production among the ceftazidime resistant
      Pseudomonas aeruginosa. A very high rate of MBL production was observed, which
      suggested it to be an important contributing factor for ceftazidime resistance
      among Pseudomonas aeruginosa. 

PMID- 24031754
TI  - Characterization of virulence genes cagA and vacA in Helicobacter Pylori and
      their prevalence in gastrointestinal disorders.
AB  - Prevalence of H. pylori infection was determined using cultures of gastric biopsy
      samples of patients attended at the academic hospital of the Federal University
      of Parana, Curitiba, Parana, Brazil. Molecular methods were used to characterize
      the cagA and vacA genes from bacterial isolates associated with different
      diseases presented by patients. Out of a total of 81, forty-two gastric biopsy
      samples tested were positive for H. pylori, with a prevalence of 51.9%. No
      significant difference was found with regard to the gender (p=0.793) and age
      (p=0.183) of the patients. Genotype s1m1 vacA gene was found in 67% of the cases
      of peptic ulcer investigated (p=1.0), despite the limited number of patients with
      this disease (n=3). A correlation between the presence of less virulent strains
      (s2m2) and reflux esophagitis was found in the majority of the cases (45%), but
      without statistical significance. An association between the prevalence of cagA
      gene, found in 92% of isolates, and peptic ulcer was not observed (p=1.0),
      suggesting that this gene cannot be considered a specific marker of severity in
      our environment. The results reinforce the importance of conducting regional
      studies and the need to characterize H. pylori virulence genes associated with
      different diseases. 

PMID- 24031755
TI  - A 7-year survey of superficial and cutaneous mycoses in a public hospital in
      Natal, Northeast Brazil.
AB  - In the present study, we determined the frequency of superficial and cutaneous
      mycoses and their etiologic agents during a 7-year period (2002-2008) in Natal,
      Brazil. A total of 1,717 specimens of skin, nail, and hair were collected from
      1,382 patients with suspected mycoses lesions and were then subjected to direct
      microscopy and culture. 

PMID- 24031756
TI  - Vulvovaginal candidiasis in Mato Grosso, Brazil: pregnancy status, causative
      species and drugs tests.
AB  - Causative agent in majority of VVC is Candida albicans, but infection due to non
      C. albicans is common. Use of empiric antifungal therapy in Brazil due to
      syndromic management of vulvovaginitis could act as risk factor for increase
      resistance among VVC causative agents. From Mato Grosso patients, 160 with
      culture-proved among 404 women who had clinical symptoms of VVC, were enrolled in
      this study. 70 non-pregnant women and 90 pregnant women were included. Candida
      albicans was the most prevalent, representing 72.9% in the non-pregnant group and
      92.3% in the pregnant group. Differences in species distribution were noted
      between the two groups, being C. parapsilosis the second more prevalent species
      among non-pregnant women. Susceptibility testing revealed high susceptibility to
      fluconazole (except for C. krusei), itraconazole, ketoconazole, and amphotericin
      B regardless the species (C. albicans, C. parapsilosis, C. tropicalis, C.
      glabrata, C. krusei) analyzed. 

PMID- 24031757
TI  - Detection of integrons among multi-drug resistant (MDR) Escherichia coli strains
      isolated from clinical specimens in northern west of Iran.
AB  - Transference of resistance determinants by integrons is one of the important
      factors that can contribute to the increase in multi-resistant bacteria. We
      determined the prevalence and class of integrons among multi-drug resistant (MDR)
      Escherichia coli strains isolated from clinical specimens in Tabriz teaching
      hospitals. Firstly, susceptibility of 140 isolates to 13 antibiotics was
      determined using the disc diffusion method. Then, prevalence and class of
      integrons was detected in MDR strains by PCR-RFLP. One hundred five (75%) of
      total 140 isolates were uropathogenic Escherichia coli (UPEC). Other pathotypes
      included were: diarrheagenic Escherichia coli (13; 9.3%), sepsis-associated E.
      coli (5; 3.6%) and newborn meningitis-associated E. coli (2; 1.4%). Antibiotic
      resistance patterns were as follows: amoxicillin 99.3%, gentamicin 33.6%,
      tetracycline 72.8%, ceftazidime 46.4%, co-trimoxazole 75%, imipenem 1.4%,
      ciprofloxacin 47.6%, norfloxacin 50.7%, cephalothin 77.8%, amikacin 12.1%,
      nitrofurantoin 12.9%, chloramphenicol 20.7% and nalidixic acid 60.7%. One hundred
      eighteen (84.2%) of tested isolates were multi-drug resistant. Prevalence of
      integrons was confirmed in 27.1% of MDR isolates. intI1 and intI2 were detected
      respectively in 22.05% and 5.08% of MDR strains. No intI3 was detected.
      Resistance to gentamicin, amikacin and chloramphenicol was significantly
      associated with the presence of integrons. These results showed high resistance
      of E. coli to routine antibiotics, however, in consideration of low prevalence of
      integrons among these strains, we can conclude that antibiotic resistance genes
      in these strains presumably carried on elements other than integrons. 

PMID- 24031758
TI  - An in-house multiplex pcr method to detect of putative virulence factors in
      aeromonas species.
AB  - A pentaplex PCR was developed and optimised to detect the genes that encode the
      five most important putative virulence factors in Aeromonas isolates. It seems to
      be more efficient than previously reported techniques and promises to be a
      powerful tool for more accurate risk assessments and for monitoring pathogenic
      strains. 

PMID- 24031759
TI  - Opportunistic microorganisms in patients undergoing antibiotic therapy for
      pulmonary tuberculosis.
AB  - Antimicrobial therapy may cause changes in the resident oral microbiota, with the
      increase of opportunistic pathogens. The aim of this study was to compare the
      prevalence of Candida, Staphylococcus, Pseudomonas and Enterobacteriaceae in the
      oral cavity of fifty patients undergoing antibiotic therapy for pulmonary
      tuberculosis and systemically healthy controls. Oral rinsing and subgingival
      samples were obtained, plated in Sabouraud dextrose agar with chloramphenicol,
      mannitol agar and MacConkey agar, and incubated for 48 h at 37 degrees C. Candida
      spp. and coagulase-positive staphylococci were identified by phenotypic tests, C.
      dubliniensis, by multiplex PCR, and coagulase-negative staphylococci,
      Enterobacteriaceae and Pseudomonas spp., by the API systems. The number of
      Candida spp. was significantly higher in tuberculosis patients, and C. albicans
      was the most prevalent specie. No significant differences in the prevalence of
      other microorganisms were observed. In conclusion, the antimicrobial therapy for
      pulmonary tuberculosis induced significant increase only in the amounts of
      Candida spp. 

PMID- 24031760
TI  - Antibiofilm activity of Cobetia marina filtrate upon Staphylococcus epidermidis
      catheter-related isolates.
AB  - We report the antibiofilm activity by the sponge-associated bacterium Cobetia
      marina upon Staphylococcus epidermidis clinical isolates obtained from central
      venous catheters. Antibiofilm activity/antimicrobial susceptibility correlation
      might predict the action of the metabolite(s) upon Staphylococcus epidermidis in
      the clinic, making it a possible adjuvant in therapies against biofilm-associated
      infections. 

PMID- 24031761
TI  - Amylase production by solid-state fermentation of agro-industrial wastes using
      Bacillus sp.
AB  - Solid state fermentation was carried out using various agro- industrial wastes
      with the best amylase producing strain isolated from soil. Different
      physicochemical conditions were varied for maximum enzyme production. The strain
      produced about 5400 units/g of amylase at 1:3 moisture content, 20% inoculum,
      after 72 h of incubation with Mustard Oil seed cake as the substrate. The optimum
      temperature and pH of the enzyme activity were found to be 50 degrees C and 6
      respectively. The enzyme was found to be thermostable at 70 degrees C for about 2
      h without any salt. It showed stability at pH range 5-7. The metal ions as Na(+),
      Ca(++), Mg(++) and Co(++) enhanced the enzyme activity. 

PMID- 24031762
TI  - Starch degradation and nutrition value improvement in corn grits by solid state
      fermentation technique with Coriolus versicolor.
AB  - The study was conducted to evaluate effect of Coriolus versicolor mycelia on
      degrading starch and improving nutrition value in corn grits through solid state
      fermentation technique. The results showed that using soybean meal as a nitrogen
      source, alpha-amylase secreted from C. versicolor expressed 407.25U/g of
      activity, leading to 45.15% of starch degraded. The activity grew with
      fermentation time until the 15(th) day, after that the amylase was deactivated
      rapidly. An orthogonal experiment designed for the study illustrated that
      degradation rate of starch in corn grits attained to maximum, 50.51%, when 100g
      of corn grits, added 16g of soybean meal, were fermented by C. versicolor for 12
      days, in an initial pH 5.5. After fermenting, compared to the nonfermented
      control, contents of amino acids, total sugar, crude fat and crude protein were
      increased by 21.00%, 38.45%, 55.56%, 69.15% respectively. The significant
      improvement of nutrition value in corn grits is probably attributed to the
      intense metabolism of C. versicolor. 

PMID- 24031763
TI  - A simple and efficient diffusion technique for assay of endo beta-1,4-xylanase
      activity.
AB  - Endo-beta-1, 4-xylanases is thought to be of great significance for several
      industries namely paper, pharmaceuticals, food, feed etc. in addition to better
      utilization of lignocellulosic biomass. The present investigation was aimed to
      develop an easy, simple and efficient assay technique for endo-beta-1, 4
      xylanases secreted by the aerobic fungi. Under the proposed protocol, 9 g/L xylan
      containing agar was prepared in 100 mM phosphate buffer at different pH (4.5, 5.5
      and 6.5). The sterilized xylan agar was dispensed in 90 mm petri dishes. 100 ul
      of culture supernatant of 12 fungal isolates was added to the wells and left
      overnight at 31+/-1(0)C. The petri dishes were observed for zone of clearance by
      naked eye and diameter was measured. Congo red solution (1 g/L) was applied over
      the petri dishes as per the established protocol and thereafter plates were
      flooded with 1M Sodium chloride solution for the appearance of zone of clearance.
      The diameter for zone of clearance by the proposed method and the established
      protocol was almost identical and ranged from 21 to 42 mm at different pH
      depending upon the activity of endo-beta-1, 4-xylanases. Change of pH towards
      alkaline side enabled similar or marginal decrease of diameter for the zone of
      clearance in most of the fungal isolates. The specific activities of these fungal
      isolates varied from 1.85 to 11.47 IU/mg protein. The present investigation
      revealed that the proposed simple diffusion technique gave similar results as
      compared to the established Congo red assay for endo-beta-1, 4-xylanases.
      Moreover, the present technique avoided the cumbersome steps of staining by Congo
      red and de-staining by sodium chloride. 

PMID- 24031764
TI  - New PHA products using unrelated carbon sources.
AB  - Polyhydroxyalkanoates (PHA) are natural polyesters stored by a wide range of
      bacteria as carbon source reserve. Due to its chemical characteristics and
      biodegradability PHA can be used in chemical, medical and pharmaceutical industry
      for many human purposes. Over the past years, few Burkholderia species have
      become known for production of PHA. Aside from that, these bacteria seem to be
      interesting for discovering new PHA compositions which is important to different
      industrial applications. In this paper, we introduce two new strains which belong
      either to Burkholderia cepacia complex (Bcc) or genomovar-type, Burkholderia
      cepacia SA3J and Burkholderia contaminans I29B, both PHA producers from unrelated
      carbon sources. The classification was based on 16S rDNA and recA partial
      sequence genes and cell wall fatty acids composition. These two strains were
      capable to produce different types of PHA monomers or precursors. Unrelated
      carbon sources were used for growth and PHA accumulation. The amount of carbon
      source evaluated, or mixtures of them, was increased with every new experiment
      until it reaches eighteen carbon sources. As first bioprospection experiments
      staining methods were used with colony fluorescent dye Nile Red and the cell
      fluorescent dye Nile Blue A. Gas chromatography analysis coupled to mass
      spectrometry was used to evaluate the PHA composition on each strain cultivated
      on different carbon sources. The synthesized polymers were composed by short
      chain length-PHA (scl-PHA), especially polyhydroxybutyrate, and medium chain
      length-PHA (mcl-PHA) depending on the carbon source used. 

PMID- 24031765
TI  - Characterization of novel extracellular protease produced by marine bacterial
      isolate from the Indian Ocean.
AB  - Out of the vast pool of enzymes, proteolytic enzymes from microorganisms are the
      most widely used in different industries such as detergent, food, peptide
      production etc. Several marine microorganisms are known to produce proteases with
      commercially desirable characteristics. We have isolated nine different cultures
      from marine samples of the Indian Ocean. All of them were i) motile ii) rod
      shaped iii) non spore forming iv) catalase and amylase positive v) able to grow
      in presence of 10 % NaCl. They produced acid from glucose, fructose and maltose
      and grew optimally at 30  degrees C temperature and pH 7.0-8.0. None of them
      could grow above 45  degrees C and below 15  degrees C. Only one of them (MBRI 7)
      exhibited extracellular protease activity on skim milk agar plates. Based on 16S
      rDNA sequencing, it belonged to the genus Marinobacter (98% sequence similarity,
      1201 bp). The cell free extract was used to study effects of temperature and pH
      on protease activity. The optimum temperature and pH for activity were found to
      be 40  degrees C and 7.0 respectively. The crude enzyme was stable at temperature
      range of 30-80  degrees C and pH 5.0-9.0. It retained 60 % activity at 80 
      degrees C after 4 h and more than 70 % activity at 70  degrees C after 1 h. D
      value was found to be 342 minutes and 78 minutes for 40  degrees C and 80 
      degrees C respectively. Interestingly the enzyme remained 50 % active at pH 9.0
      after 1 h. Comparison with other proteases from different microbial sources
      indicated that the neutral protease from the halotolerant marine isolate MBRI 7
      is a novel enzyme with high thermostability. 

PMID- 24031766
TI  - Modification of c and n sources for enhanced production of cyclosporin 'a' by
      Aspergillus Terreus.
AB  - Most of the studies regarding cyclosporin 'A' production through fungi
      concentrate around Tolypocladium inflatum. This is mainly due to lower reported
      production of this drug in other fungi. The present study was therefore conducted
      to explore indigenous isolates of Aspergillus terreus for synthesis of this drug
      and defining a production medium for obtaining high yield of cyclosporin 'A'. For
      this purpose carbon and nitrogen sources were optimized for the selected best
      strain of A. terreus. Overall results depicted that the best cyclosporin 'A'
      yield from selected Aspergillus terreus (FCBP58) could be obtained by using
      production medium containing glucose 10% as carbon source and peptone 0.5% as
      nitrogen source. This modification in production medium enhanced drug synthesis
      by selected fungi significantly. The production capabilities when compared with
      biomass of fungi there was found no relationship between the two confirming that
      the medium modification increased overall drug synthesis powers of the fungi. 

PMID- 24031767
TI  - Brewer's spent grain and corn steep liquor as alternative culture medium
      substrates for proteinase production by Streptomyces malaysiensis AMT-3.
AB  - Brewer's spent grain and corn steep liquor or yeast extract were used as the sole
      organic forms for proteinase production by Streptomyces malaysiensis in submerged
      fermentation. The influence of the C and N concentrations, as well as the
      incubation periods, were assessed. Eight proteolytic bands were detected through
      gelatin-gel-electrophoresis in the various extracts obtained from the different
      media and after different incubation periods, with apparent molecular masses of
      20, 35, 43, 50, 70, 100, 116 and 212 kDa. The results obtained suggest an
      opportunity for exploring this alternative strategy for proteinases production by
      actinomycetes, using BSG and CSL as economically feasible substrates. 

PMID- 24031768
TI  - Influence of culture medium on the production of eif antigen from Leishmania
      chagasi in recombinant Escherichia coli.
AB  - With the advent of recombinant DNA technology, recombinant protein expression has
      become an important tool in the study of the structure, function and
      identification of new proteins, especially those with therapeutic functions.
      Escherichia coli has been the predominant prokaryote used in genetic engineering
      studies due to the abundance of information about its metabolism. Despite
      significant advances in molecular biology and immunology of infections, there are
      as yet no prophylactic drugs capable of preventing visceral leishmaniasis. It is
      therefore important to identify specific antigens in order to develop vaccines
      and diagnostic kits against this disease. The objective of this study was to
      evaluate the influence of culture medium on the production of eIF antigen from
      Leishmania chagasi in recombinant Escherichia coli. An induction procedure using
      IPTG was carried out in a series of trials, to observe the influence of culture
      medium (2xTY, TB) under expression of the recombinant eIF protein. Results showed
      that recombinant protein expression was associated to growth and that the highest
      eIF antigen expression was obtained in the 2xTY medium. 

PMID- 24031769
TI  - Comparative study on production of a-Amylase from Bacillus licheniformis strains.
AB  - Alpha amylase (alpha-1, 4-glucan-glucanhydrolase, EC 3.2.1.1), an extracellular
      enzyme, degrades alpha, 1-4 glucosidic linkages of starch and related substrates
      in an endo-fashion producing oligosaccharides including maltose, glucose and
      alpha limit dextrin (7). The present study deals with the production and
      comparative study of production of alpha-amylase from two strains of Bacillus
      licheniformis, MTCC 2617 and 2618, by using four different substrates, starch,
      rice, wheat and ragi powder as carbon source by submerged fermentation. The
      effect of varying pH and incubation temperature, activator, inhibitor, and
      substrate concentration was investigated on the activity of alpha-amylase
      produced by MTCC strain 2618. The results shows that the production of the alpha
      amylase by the B.licheniformis strain MTCC 2618, using four different substrates
      were found to be maximum (Starch 3.64 IU/ml/minutes, Rice powder 2.93
      IU/ml/minutes, Wheat powder 2.67 IU/ml/minutes, Ragi powder 2.36 IU/ml/minutes)
      on comparing the enzyme production of two strains. It was also observed that the
      maximum production was found on the 3(rd) day (i.e. 72 hr) and characterization
      of crude enzyme revealed that optimum activity was at pH 7 and 37 degrees C. 

PMID- 24031770
TI  - Brucella canis infection in dogs attended in veterinary clinics from patos,
      ParabaIBA state, Brazil.
AB  - To determine the frequency of anti-Brucella canis antibodies in dogs attended in
      veterinary clinics from Patos, Paraiba State, Brazil, as well as to identify risk
      factors and to isolate and identify the agent, 193 dogs were used. Agar gel
      immunodiffusion test (AGID) was used to detect B. canis antibodies in sera.
      Isolation of B. canis was carried out in blood and bone marrow from seropositive
      animals. Six animals tested seropositive in AGID, resulting in a frequency of
      3.11%. B. canis was isolated from bone marrow of one seropositive animal, with
      confirmation by PCR. Lack of cleaning of the dog's environment was identified as
      risk factor (odds ratio = 7.91). This is the first report of isolation of B.
      canis in dogs from the Northeast region of Brazil. 

PMID- 24031771
TI  - Requirement for cobalamin by Salmonella enterica serovars Typhimurium, Pullorum,
      Gallinarum and Enteritidis during infection in chickens.
AB  - Salmonella enterica serovar Typhimurium synthesizes cobalamin (vitamin B12) only
      during anaerobiosis. Two percent of the S. Typhimurium genome is devoted to the
      synthesis and uptake of vitamin B12 and to B12-dependent reactions. To understand
      the requirement for cobalamin synthesis better, we constructed mutants of
      Salmonella serovars Enteritidis and Pullorum that are double-defective in
      cobalamin biosynthesis (DeltacobSDeltacbiA). We compared the virulence of these
      mutants to that of their respective wild type strains and found no impairment in
      their ability to cause disease in chickens. We then assessed B12 production in
      these mutants and their respective wild type strains, as well as in S.
      Typhimurium DeltacobSDeltacbiA, Salmonella Gallinarum DeltacobSDeltacbiA, and
      their respective wild type strains. None of the mutants was able to produce
      detectable B12. B12 was detectable in S. Enteritidis, S. Pullorum and S.
      Typhimurium wild type strains but not in S. Gallinarum. In conclusion, the
      production of vitamin B12 in vitro differed across the tested Salmonella
      serotypes and the deletion of the cbiA and cobS genes resulted in different
      levels of alteration in the host parasite interaction according to Salmonella
      serotype tested. 

PMID- 24031772
TI  - ERIC-PCR genotypic characterization of Haemophilus parasuis isolated from
      Brazilian swine.
AB  - Haemophilus parasuis infection, known as Glasser's disease, is characterized by
      fibrinous polyserositis, arthritis and meningitis in piglets. Although
      traditional diagnosis is based on herd history, clinical signs, bacterial
      isolation and serotyping, the molecular-based methods are alternatives for
      species-specific tests and epidemiologic study. The aim of this study was to
      characterize H. parasuis strains isolated from different states of Brazil by
      serotyping, PCR and ERIC-PCR. Serotyping revealed serovar 4 as the most prevalent
      (24 %), followed by serovars 14 (14 %), 5 (12 %), 13 (8 %) and 2 (2 %), whereas
      40 % of the strains were considered as non-typeable. From 50 strains tested 43
      (86%) were positive to Group 1 vtaA gene that have been related to virulent
      strains of H.parasuis. ERIC-PCR was able to type isolates tested among 23
      different patterns, including non-typeable strains. ERIC-PCR patterns were very
      heterogeneous and presented high similarity between strains of the same animal or
      farm origin. The results indicated ERIC-PCR as a valuable tool for typing H.
      parasuis isolates collected in Brazil. 

PMID- 24031773
TI  - Seroprevalence and risk factors of antibodies against Leptospira spp. in ovines
      from Uberlandia municipality, Minas Gerais state, Brazil.
AB  - The objectives of the present study were to verify the seroprevalence of anti
      Leptospira spp. antibodies, identify the most frequent serovars and the risk
      factors associated with the infection in Uberlandia, Minas Gerais, Brazil. A
      total of 334 ovines blood samples were collected in 12 farms from Uberlandia
      municipality to be evaluated by means the Microscopic Agglutination Test (MAT)
      against 22 serovars of Leptospira spp. and an epidemiologic questionnaire was
      applied for each farm in order to correlate with risk factors of leptospirosis:
      sex, age and breed as well as contact with cattle, contact with dogs and presence
      of rodents. The prevalence of seropositive to MAT was found in seventy four
      ovines (22.2%; CI 95% 17.6-26.4%), with titers ranging from 100 to 3200. The most
      frequent serovars identified were: Hardjo, Autumnalis, Hardjo and Wolffi
      association and Grippotyphosa. Statistically significant differences were found
      in males, pure breeds and presence of rodents (p<0.05). The prevalence of anti
      Leptospira spp. antibodies found in the present study demonstrated that this
      bacterium occurs in ovines of Uberlandia municipality, MG, Brazil. The need for
      the adoption of efficient management for the control of rodents and infection in
      ovines in order to avoid leptospirosis in the local flocks and future
      transmission to humans. 

PMID- 24031774
TI  - In vitro antimicrobial resistance of Pseudomonas aeruginosa isolated from canine
      otitis externa in Rio de Janeiro, Brazil.
AB  - Isolates of Pseudomonas aeruginosa (167) were obtained from 528 samples of canine
      otitis externa, identified by biochemical reactions and tested for susceptibility
      to 10 antimicrobials. The most effective drug was ciprofloxacin. The study
      reports alarming resistance among P. aeruginosa isolated from canine otitis
      externa samples in Rio de Janeiro, Brazil. 

PMID- 24031775
TI  - Mycobacterium bovis infection in goats from the Northeast region of Brazil.
AB  - A total of 8,058 male and female mixed-breed goats and 1-4 years of age were
      slaughtered over a period of 7 months at the public slaughterhouse of Patos city,
      Paraiba state, in the Northeast region of Brazil; 822 animals were inspected for
      gross lesions of tuberculosis, and 12 (1.46%) had lesions suggestive of
      tuberculosis in the mammary gland, lungs, liver and mediastinal, mesenteric,
      submandibular, parotid and prescapular lymph nodes. Presence of granulomatous
      lesions was confirmed in the submandibular lymph node of one (8.3%) goat at the
      histopathological examination and at the mycobacterium culture the same sample
      was confirmed positive. Isolate was confirmed as belonging to the M. tuberculosis
      complex by PCR restriction enzyme analysis (PRA). Spoligotyping identified the
      isolate into spoligotype SB0295 on the M. bovis Spoligotype Database website
      (www.mbovis.org), and it was classified as M. bovis. The occurrence of M. bovis
      in goats in this study suggests that this species may be a potential source of
      infection for humans and should be regarded as a possible problem in the
      advancement of control and eradication program for bovine tuberculosis in Brazil.

PMID- 24031776
TI  - Phylogenetic characterization of bovine parainfluenza 3 from contaminated cell
      cultures and field isolates from Brazil.
AB  - Genomic fragments of the HN and L genes from Brazilian bovine parainfluenza 3
      virus (bPIV-3) isolated as contaminants from cell cultures and clinical specimens
      were amplified by reverse transcription-polymerase chain reaction (RT-PCR),
      sequenced using specific degenerate primers and analyzed by phylogenetic
      comparison with reference strains of bPI3V. The Brazilian isolates revealed a
      high degree of genomic when compared to SF4/32 prototype strain, within the
      recently proposed genotype A of bPIV-3. 

PMID- 24031777
TI  - Biocontrol of pigeon tick Argas reflexus (Acari: Argasidae) by entomopathogenic
      fungus Metarhizium Anisopliae (Ascomycota: Hypocreales).
AB  - The pigeon tick Argas reflexus is a pathogen-transmitting soft tick that
      typically feeds on pigeons, but can also attack humans causing local and systemic
      reactions. Chemical control is made difficult due to environmental contamination
      and resistance development. As a result, there is much interest in increasing the
      role of other strategies like biological control. In this study, the efficacy of
      three strains (V245, 685 and 715C) of entomopathogenic fungus Metarhizium
      anisopliae for biological control of three life stages of pigeon tick A. reflexus
      including eggs, larvae, engorged and unfed adults was investigated under
      laboratory conditions. Five concentrations of different strains of M. anisopliae
      ranging from 10(3) to 10(7) conidia/ml were used. All fungal strains
      significantly decreased hatchability of A. reflexus eggs. Strain V245 was the
      most effective strain on the mortality of larval stage with nearly 100% mortality
      at the lowest concentration (10(3) conidia/ml) at 10 days post-inoculation. The
      mortality rate of both engorged and unfed adult ticks were also increased
      significantly exposed to different conidial concentrations compared to the
      control groups (P < 0.05) making this fungus a potential biological control agent
      of pigeon tick reducing the use of chemical acaricides. 

PMID- 24031778
TI  - Antibacterial properties and chemical characterization of the essential oils from
      summer savory extracted by microwave-assisted hydrodistillation.
AB  - Antibacterial properties and chemical characterization of the essential oils from
      summer savory (Satureja hortensis) extracted by microwave-assisted
      hydrodistillation (MAHD) were compared with those of the essential oils extracted
      using the traditional hydrodistillation (HD) method. While MAHD at 660 W required
      half as much time as HD needed, similar antibacterial efficacies were found from
      the essential oils obtained by the two extraction methods on two food pathogens
      (Staphylococcus aureus, a gram positive bacterium, and Escherchia coli, a gram
      negative bacterium). Also, as it was the case with the essential oils extracted
      by HD, that of MAHD indicated greater influence on S. aureus than on E. coli. The
      compositions of the extracted essential oils were also studied using GC-MS
      analysis. The same components with negligible differences in their quantities
      were found in the extracted essential oils using the two methods outlined above.
      Overall, to reduce the extraction time, MAHD can be applied at higher microwave
      levels without any compromise in the antibacterial properties of the essential
      oils extracted. 

PMID- 24031779
TI  - Antibiotic resistance of Vibrio parahaemolyticus isolated from pond-reared
      Litopenaeus vannamei marketed in natal, brazil.
AB  - Ten out of fifty fresh and refrigerated samples of shrimp (Litopenaeus vannamei)
      collected from retailers in Natal (Rio Grande do Norte, Northeastern Brazil)
      tested positive for Vibrio parahaemolyticus. The Kanagawa test and multiplex PCR
      assays were used to detect TDH and TRH hemolysins and the tdh, trh and tlh genes,
      respectively. All strains were Kanagawa-negative and tlh-positive. Antibiotic
      susceptibility testing was done for seven antibiotics by the agar diffusion
      technique. Five strains (50%) presented multiple antibiotic resistance to
      ampicillin (90%) and amikacin (60%), while two strains (20%) displayed
      intermediate-level resistance to amikacin. All strains were sensitive to
      chloramphenicol. Intermediate-level susceptibility and/or resistance to other
      antibiotics ranged from 10 to 90%, with emphasis on the observed growing
      intermediate-level resistance to ciprofloxacin. Half our isolates yielded a
      multiple antibiotic resistance index above 0.2 (range: 0.14-0.29), indicating a
      considerable risk of propagation of antibiotic resistance throughout the food
      chain. 

PMID- 24031780
TI  - Growth and exopolysaccharide production by Streptococcus thermophilus ST1 in skim
      milk.
AB  - To analyze the exopolysaccharide (EPS) production by Streptococcus thermophilus
      ST1, cultures were cultivated in 10% (w/v) reconstituted skim milk under
      different growth conditions including various temperatures and pHs of growth
      medium, supplementation of the medium with various carbon sources (glucose,
      lactose, sucrose, galactose and fructose) and nitrogen source (whey protein
      concentrate, or WPC). The results showed that most EPS production by strain ST1
      was obtained at a temperature (42 degrees C) and pH (6.5) optimal for its growth.
      Supplementation of the skim milk medium with either carbohydrates or WPC
      increased both growth and polymer formation by different extents, with sucrose
      being most effective among the carbon sources tested. Under the optimal cultural
      conditions, i.e. pH 6.5, 42 degrees C with 2% (w/v) sucrose and 0.5% (w/v) WPC,
      135.80 mg l(-1) of EPS was produced by strain ST1. The monosaccharide composition
      of the EPS was determined to be glucose and galactose (2:1), and the molecular
      mass of the EPS was 3.97 * 10(6) Da. The aqueous solution of the EPS at 1% (w/v)
      showed relatively high viscosity, indicating the potential of this EPS-producing
      S. thermophilus strain for applications in the improvement of physical properties
      of fermented milk products. 

PMID- 24031781
TI  - Hydrolytic potential of a psychrotrophic Pseudomonas isolated from refrigerated
      raw milk.
AB  - The production of extracellular hydrolases by a psychrotrophic bacterium isolated
      from refrigerated raw milk, and identified as a Pseudomonas sp. belonging to the
      Pseudomonas jenssenii group, was studied. This bacterium produced proteolytic and
      lipolytic enzymes in all media investigated (skim milk, cheese whey, casein
      broth, and tryptone soy broth). High levels of alpha-glucosidase were produced in
      skim milk broth. Hydrolytic enzymes detected in skim milk broth are of particular
      concern, indicating that these enzymes could be produced by Pseudomonas sp.
      during the cold storage of raw milk, contributing to the spoilage problem in milk
      and dairy products. 

PMID- 24031783
TI  - Effect of ph and salt gradient on the autolysis of Lactococcus lactis strains.
AB  - The aim of this work was to assess in-vitro the effect of pH and salt
      concentration on the rate of autolysis in L. lactis strains. Regardless autolysis
      variation among L. lactis strains, statistical analysis showed evidence of
      increase of autolysis in L. lactis under low salt concentration and acidic
      conditions. 

PMID- 24031782
TI  - Application of response surface methodology to enhancement of biomass production
      by Lactobacillus rhamnosus E/N.
AB  - Response surface methodology (RSM) was employed to study the effects of various
      medium components on biomass production by Lactobacillus rhamnosus E/N. This
      strain is commonly used in the pharmaceutical and food industries due to its
      beneficial effect on the human gut and general health. The best medium
      composition derived from RSM regression was (in g/l) glucose 15.44, sodium
      pyruvate 3.92, meat extract 8.0, potassium phosphate 1.88, sodium acetate 4.7,
      and ammonium citrate 1.88. With this medium composition biomass production was 23
      g/l of dry cell weight after 18 h of cultivation in bioreactor conditions,
      whereas on MRS the yield of biomass was 21 g/l of dry cell weight. The cost of 1
      g of biomass obtained on MRS broth was calculated at the level of 0.44 ? whereas
      on the new optimal medium it was 25% lower. It may be concluded then, that the
      new medium, being cheaper than the control MRS allows large scale commercial
      cultivation of the L. rhamnosus strain. This study is of relevance to food
      industry because the possibility to obtain high yield of bacterial biomass is
      necessary step in manufacturing of probiotic food. 

PMID- 24031784
TI  - Effect of freeze drying process on some properties of Streptococcus thermophilus
      isolated from dairy products.
AB  - The present investigation represents the effect of freeze drying on some
      properties as acid and bile tolerance of Streptococcus thermophilus MTCC 1938
      culture isolated from dairy products. The cell paste obtained from milk based
      medium was freeze dried with a pressure of 50-100 mtorr for 24h at -40 degrees C.
      Acid and bile tolerance test exhibited 3.8-4.9 and 3.2-3.8 log counts reduction
      after freeze drying respectively. 

PMID- 24031785
TI  - Optimization studies on production of a salt-tolerant protease from Pseudomonas
      aeruginosa strain BC1 and its application on tannery saline wastewater treatment.
AB  - Treatment and safe disposal of tannery saline wastewater, a primary effluent
      stream that is generated by soaking salt-laden hides and skin is one of the major
      problems faced by the leather manufacturing industries. Conventional treatment
      methods like solar evaporation ponds and land composting are not eco-friendly as
      they deteriorate the ground water quality. Though, this waste stream is comprised
      of high concentration of dissolved proteins the presence of high salinity (1-6 %
      NaCl by wt) makes it non-biodegradable. Enzymatic treatment is one of the
      positive alternatives for management of such kind of waste streams. A novel salt
      tolerant alkaline protease obtained from P.aeruginosa (isolated from tannery
      saline wastewater) was used for enzymatic degradation studies. The effect of
      various physical factors including pH, temperature, incubation time, protein
      source and salinity on the activity of identified protease were investigated.
      Kinetic parameters (Km , Vmax) were calculated for the identified alkaline
      protease at varying substrate concentrations. Tannery saline wastewater treated
      with identified salt tolerant protease showed 75 % protein removal at 6 h
      duration and 2 % (v/v) protease addition was found to be the optimum dosage
      value. 

PMID- 24031786
TI  - Isolation and characterization of potential lactic acid bacteria (LAB) from
      freshwater fish processing wastes for application in fermentative utilisation of
      fish processing waste.
AB  - Proteolytic and/or lipolytic lactic acid bacteria (LAB) were isolated from
      visceral wastes of different fresh water fishes. LAB count was found to be
      highest in case of visceral wastes of Mrigal (5.88 log cfu/g) and lowest in that
      of tilapia (4.22 log cfu/g). Morphological, biochemical and molecular
      characterization of the selected LAB isolates were carried out. Two isolates FJ1
      (E. faecalis NCIM5367) and LP3 (P. acidilactici NCIM5368) showed both proteolytic
      and lipolytic properties. All the six native isolates selected for
      characterization showed antagonistic properties against several human pathogens.
      All the native isolates were sensitive to antibiotics cephalothin and
      clindamycin; and, resistant to cotrimoxazole and vancomycin. Considering
      individually, P. acidilactici FM37, P. acidilactici MW2 and E. faecalis FD3 were
      sensitive to erythromycin. The two strains FJ1 (E. faecalis NCIM 5367) and LP3
      (P. acidilactici NCIM 5368) that had both proteolytic and lipolytic properties
      have the potential for application in fermentative recovery of lipids and
      proteins from fish processing wastes. 

PMID- 24031787
TI  - Mycoremediation of congo red dye by filamentous fungi.
AB  - Azo, anthroquinone and triphenylmethane dyes are the major classes of synthetic
      colourants, which are difficult to degrade and have received considerable
      attention. Congo red, a diazo dye, is considered as a xenobiotic compound, and is
      recalcitrant to biodegradative processes. Nevertheless, during the last few years
      it has been demonstrated that several fungi, under certain environmental
      conditions, are able to transfer azo dyes to non toxic products using laccases.
      The aim of this work was to study the factors influencing mycoremediation of
      Congo red. Several basidiomycetes and deuteromycetes species were tested for the
      decolourisation of Congo red (0.05 g/l) in a semi synthetic broth at static and
      shaking conditions. Poor decolourisation was observed when the dye acted as the
      sole source of nitrogen, whereas semi synthetic broth supplemented with
      fertilizer resulted in better decolourisation. Decolourisation of Congo red was
      checked in the presence of salts of heavy metals such as mercuric chloride, lead
      acetate and zinc sulphate. Decolourisation parameters such as temperature, pH,
      and rpm were optimized and the decolourisation obtained at optimized conditions
      varied between 29.25- 97.28% at static condition and 82.1- 100% at shaking
      condition. Sodium dodecyl sulphate polyacrylamide gel electrophoretic analysis
      revealed bands with molecular weights ranging between 66.5 to 71 kDa, a
      characteristic of the fungal laccases. High efficiency decolourisation of Congo
      red makes these fungal forms a promising choice in biological treatment of waste
      water containing Congo red. 

PMID- 24031788
TI  - Chemical characterization of Lippia alba essential oil: an alternative to control
      green molds.
AB  - The essential oil of Lippia alba is reported as an antifungal against human
      pathogenic microorganisms but few articles report its use as an alternative to
      synthetic fungicides on green mould control. The objective of this study was to
      determine chemical characteristics of L. alba essential oil and its antifungal
      activity against green molds as an alternative to synthetic fungicides. Essential
      oil was extracted by Clevenger hydrodistillation, characterized by GC-MS
      analysis, and the structure of the main compounds confirmed by (1)H and (13)C-NMR
      spectroscopy. Microdilution assays evaluated the essential oil minimum inhibitory
      concentration (MIC) and minimum fungicidal concentration (MFC). Commercial
      fungicides Ketoconazole and Bifonazole were used as control. Essential oil yield
      is of 0.15% and the major components are neral (33.32%) and geranial (50.94%).
      The L. alba essential oil has MIC of 0.300-1.250 mg/mL and MFC of 0.600-1.250
      mg/mL. Ketoconazole and Bifonazole show MIC ranging from 0.025-0.500 to 0.100
      0.200 mg/mL, and MFC ranging from 0.250-0.100 to 0.200-0.250 mg/mL, respectively.
      L. alba essential oil is classified as citral type and the results indicate that
      it is a potential alternative to synthetic fungicides. 

PMID- 24031789
TI  - The inhibitory effect of calcium on Cylindrospermopsis raciborskii
      (cyanobacteria) metabolism.
AB  - Cylindrospermopsis raciborskii (Woloszynska) Seenaya & Subba Raju is a freshwater
      cyanobacterium of worldwide distribution. In the North-eastern region of Brazil
      many eutrophic water reservoirs are characterized by the dominance of C.
      raciborskii, with recurrent occurrence of blooms. These water bodies have high
      conductivity due to a high ionic concentration, and are defined as hard (with
      high values of CaCO3). In this study, we investigated the long-term effect (12
      days) of high calcium concentration (8 mM Ca(2+)) on C. raciborskii (T3 strain)
      growth, morphology, toxin content, and metabolism. Changes in protein expression
      profiles were investigated by proteomic analysis using 2D gel electrophoresis and
      mass spectrometry. A continued exposure to calcium had a pronounced effect on C.
      raciborskii (T3): it limited growth, decreased thricome length, increased
      chlorophyll-a content, altered toxin profile (although did not affect PST
      content, saxitoxin + neosaxitoxin), and inhibited the expression of proteins
      related to primary metabolism. 

PMID- 24031790
TI  - Isolation and cultivation of fungal strains from in vitro cell cultures of two
      marine sponges (Porifera: Halichondrida and Haplosclerida).
AB  - Despite the large number of reports describing sponge-microbe associations,
      limited knowledge is available about associated fungi and their relationships
      with the hosts. In this work, specific fungal strains were obtained directly from
      in vitro sponge cell cultures (primmorphs) and single sponge cells (cytospins)
      and compared with those obtained from whole tissue preparations. A total of 27
      fungal strains were isolated from the marine sponges Hymeniacidon heliophila and
      Haliclona melana. Fifteen strains, nine from H. heliophila and six from H.
      melana, were obtained from whole tissue and were considered as possible mesohyl
      associated or transient fungi. Twelve strains were isolated from in vitro sponge
      cell cultures (primmorphs) and were, therefore, considered as cell associated.
      From these, five different strains were obtained from H. heliophila isolated
      cells, while five were identified from cytospins and two from primmorphs of H.
      melana. The fungal strains obtained from cell cultures from both sponge species
      were different, and none of them were detected in the whole tissue preparations
      of the same species. Nine H. heliophila and seven H. melana strains shows low
      similarity with the sequences available in public databases and belong to
      potentially new species. This is the first report of fungi isolated directly from
      sponge cells, which allowed the observation and selection of specific strains
      that probably would not be obtained by usual culture dependent techniques. 

PMID- 24031791
TI  - Phytochemical screening and antimicrobial activity of roots of Murraya koenigii
      (Linn.) Spreng. (Rutaceae).
AB  - Murraya koenigii, family Rutaceae, commonly known as Curry leaf plant is a highly
      valued plant for its medicinal value and characteristic aroma. The plant is a
      rich source of carbazole alkaloids. The petroleum ether, chloroform, ethyl
      acetate and ethanol extracts of roots of the plant were screened for
      phytochemical properties and antimicrobial activity for Staphylococcus aureus,
      Micrococcus luteus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa,
      Candida albicans and Aspergillus niger. Phytochemical screening showed the
      presence of carbohydrates, alkaloids, steroids and flavonoids in the root
      extracts of the plant. The study shows that all the extracts possess remarkable
      antibacterial activity. Additionally, petroleum ether and chloroform extracts
      also had antifungal activity. 

PMID- 24031792
TI  - A novel method to optimize culture conditions for biomass and sporulation of the
      entomopathogenic fungus Beauveria bassiana IBC1201.
AB  - Biomass yields and sporulation of Beauveria bassiana was concerned on culture
      conditions, environmental factors and cultivation method. We optimized the best
      culture conditions for biomass yields of B. bassiana IBC1201 with the novel "two
      stage" cultivation method as well as orthogonal matrix method. Firstly, we
      cultured spore suspension on the basal medium (sucrose 19.00 g, soy peptone 4.06
      g, K2HPO4 1.00 g, KCl 0.50 g, MgSO4 0.50 g, FeSO4 0.10 g and 17.00 g Bactor) for
      the first stage culture of 4 days under room condition. Then, we transferred them
      to another defined medium (Cellobiose 9.52 g, urea 1.70 g, ZnSO4*7H2O 0.05 g/L,
      MnSO4*H2O 0.005 g/L, CaCl2 1.00 g/L, CuSO4*5H2O 0.05 g/L and 17.00 g Bactor) for
      more 4 days cultivation with the environmental factors combination of water
      potential -1.2 MPa /pH 3 /12 h light cycle/23 C for biomass yields, and with the
      environmental factors combination of water potential -0.8 MPa /pH 3 /24 h light
      cycle/23 C for spore yields. These results provided important information for
      mass production (including biomass and spore yields) of this great potential
      biocontrol fungus. 

PMID- 24031793
TI  - Xylanase production by Aspergillus awamori under solid state fermentation
      conditions on tomato pomace.
AB  - In this work, tomato pomace, a waste abundantly available in the Mediterranean
      and other temperate climates agro-food industries, has been used as raw material
      for the production of some hydrolytic enzymes, including xylanase, exo
      polygalacturonase (exo-PG), cellulase (CMCase) and alpha-amylase. The principal
      step of the process is the solid state fermentation (SSF) of this residue by
      Aspergillus awamori. In several laboratory experiments, maximum xylanase and exo
      PG activities were measured during the first days of culture, reaching values
      around 100 and 80 IU/gds (international units of enzyme activity per gram of
      dried solid), respectively. For CMCase and alpha-amylase production remained
      almost constant along fermentation, with average values of 19 and 21.5 IU/gds,
      respectively. Experiments carried out in a plate-type bioreactor at lab scale
      showed a clear positive effect of aeration on xylanase and CMCase, while the
      opposite was observed for exo-PG and alpha-amylase. In general, xylanase was the
      enzyme produced in higher levels, thus the optimum conditions for the
      determination of the enzyme activity was characterized. The xylanase activity
      shows an optimum pH of 5 and an optimum temperature of 50 oC. The enzyme is
      activated by Mg(2+), but strongly inhibited by Hg(2+) and Cu(2+). The enzymatic
      activity remains quite high if the extract is preserved in a range of pH from 3
      to 10 and a temperature between 30 oC to 40 oC. 

PMID- 24031794
TI  - Exploitation of Trichoderma species on the growth of Pythium Aphanidermatum in
      Chilli.
AB  - Damping-off of chilli caused by Pythium aphanidermatum is a major nursery disease
      in vegetables. In vitro experiments evaluated the effect of eight isolates of
      Trichoderma species (from chilli rhizosphere) were tested against P.
      aphanidermatum. All the Trichoderma species had varied antagonistic effects
      against the pathogen. Among them, TVC3 recorded maximum growth inhibition of P.
      aphanidermatum and produced more amounts of volatile and non-volatile
      metabolites. The culture filtrate of the Trichoderma isolate TVC3 recorded
      complete inhibition on the mycelial growth of pathogen at 15% concentration.
      Moreover, chilli seeds treated with culture filtrate of the isolate TVC3 recorded
      maximum germination percentage, shoot length, root length and vigour index of
      chilli. The study identified the Trichoderma isolate (TVC3) performed well in
      inhibiting the mycelial growth of pathogen as well as increased the plant growth
      in chilli. 

PMID- 24031795
TI  - Cellulolytic potential of a novel strain of Paenibacillus sp. isolated from the
      armored catfish Parotocinclus maculicauda gut.
AB  - A cellulolytic bacterial strain, designated P118, isolated from the gut of the
      tropical fish Parotocinclus maculicauda was identified as belonging to the genus
      Paenibacillus based on phenotypic and chemotaxonomic characteristics and the 16S
      rRNA gene sequence. The novel strain was Gram-positive, spore-forming and rod
      shaped. Catalase but not oxidase was produced. Carboxymethylcellulose was
      hydrolyzed but starch or gelatin was not. Acetoin production was negative whereas
      nitrate reduction and urease production were positive. Many carbohydrates served
      as carbon sources for growth. MK-7 was the predominant isoprenoid quinone.
      Anteiso-C15:0 (38.73%) and C16:0 (20.85%) were the dominant cellular fatty acids.
      Strain P118 was closely related to Paenibacillus amylolyticus NRRL NRS-290, P.
      pabuli HSCC 492, P. tundrae Ab10b, P. xylanexedens B22a, and P. tylopili MK2 with
      98.3-98.8% 16S rRNA gene sequence similarity. The results presented here suggest
      that strain P118 represents a novel species of the genus Paenibacillus and it is
      a potential strain for further studies concerning its role in the production of
      industrially important products from cellulosic biomass. 

PMID- 24031796
TI  - Antiviral activity of the Lippia graveolens (Mexican oregano) essential oil and
      its main compound carvacrol against human and animal viruses.
AB  - Mexican oregano (Lippia graveolens) is a plant found in Mexico and Central
      America that is traditionally used as a medicinal herb. In the present study, we
      investigated the antiviral activity of the essential oil of Mexican oregano and
      its major component, carvacrol, against different human and animal viruses. The
      MTT test (3-4,5-dimethythiazol-2yl)-2,5-diphenyl tetrazolium bromide) was
      conducted to determine the selectivity index (SI) of the essential oil, which was
      equal to 13.1, 7.4, 10.8, 9.7, and 7.2 for acyclovir-resistant herpes simplex
      virus type 1 (ACVR-HHV-1), acyclovir-sensitive HHV-1, human respiratory syncytial
      virus (HRSV), bovine herpesvirus type 2 (BoHV-2), and bovine viral diarrhoea
      virus (BVDV), respectively. The human rotavirus (RV) and BoHV-1 and 5 were not
      inhibited by the essential oil. Carvacrol alone exhibited high antiviral activity
      against RV with a SI of 33, but it was less efficient than the oil for the other
      viruses. Thus, Mexican oregano oil and its main component, carvacrol, are able to
      inhibit different human and animal viruses in vitro. Specifically, the antiviral
      effects of Mexican oregano oil on ACVR-HHV-1 and HRSV and of carvacrol on RV
      justify more detailed studies. 

PMID- 24031797
TI  - Limited vegetative compatibility as a cause of somatic recombination in
      Trichoderma pseudokoningii.
AB  - With the aim of a better characterization of the somatic recombination process in
      Trichoderma pseudokoningii, a progeny from crossings between T. pseudokoningii
      strains contrasting for auxotroph markers was characterized by RAPD markers and
      PFGE (electrophoretic karyotype). Cytological studies of the conidia,
      conidiogenesis and heterokaryotic colonies were also performed. The genotypes of
      the majority of the recombinant strains analyzed were similar to only one of the
      parental strains and the low frequency of polymorphic RAPD bands suggested that
      the nuclear fusions may not occur into the heterokaryon. In some heterokaryotic
      regions the existence of intensely staining hyphae might be related to cell
      death. We proposed that a mechanism of somatic recombination other than
      parasexuality might occur, being related to limited vegetative compatibility
      after postfusion events, as described for other Trichoderma species. 

PMID- 24031798
TI  - Physiological studies on carboxymethyl cellulase formation by Aspergillus terreus
      DSM 826.
AB  - Physiological studies were conducted to determine the optimum cultural conditions
      for maximal carboxymethyl cellulase (CMCase) formation by Aspergillus terreus DSM
      826. Shaking condition at 150 rpm is favorable for the production of CMCase from
      rice straw and sugar cane bagasse. The highest enzyme yield was obtained at the
      third day of incubation at 30  degrees C for both cases; however CMCase formation
      occurred at a broad range of pH values, with maximal formation of A. terreus DSM
      826 CMCase at pH 4.5 and 5.0 when rice straw and sugar cane bagasse were used as
      sole carbon source, respectively. Carboxymethyl cellulose (CMC) was found to be a
      good inducer for CMCase formation in both agricultural wastes with CMC
      concentrations of 0.5 and 1.0 % (w/v) in case of rice straw and sugar cane
      bagasse, respectively. High level of enzyme formation was obtained with the
      addition of ammonium chloride as nitrogen source in both cases and at a
      concentration of 0.4 % (v/v Tween-80) as an addition to medium containing rice
      straw. However this addition did not influence the production of CMCase in case
      of using sugar cane bagasse as carbon source. 

PMID- 24031799
TI  - Aeration effect on Spirulina platensis growth and gamma-Linolenic acid
      production.
AB  - The influence of aeration on algal growth and gamma-linolenic acid (GLA)
      production in a bubble column photobioreactor was investigated. Studies were
      performed in a 20-L reactor at different aeration rates (0.2- 2.5 vvm). Static,
      continuous, and periodic operation of air resulted in 41.9%, 88.4%, and 108% air
      saturation of dissolved oxygen, for which the corresponding values of GLA were
      2.3, 6.5, and 7.5 mg.g(-1) dry cell weight, respectively. An increase in the
      aeration rate from 0.2 to 2.5 vvm enhanced both the specific growth rate and GLA
      content under periodic sparging in the bicarbonate medium. With a 6-fold increase
      in the aeration rate, the GLA content of the alga increased by 69.64% (5.6-9.5
      mg. g(-1) dry cell weight). In addition, the total fatty acid (TFA) content in
      dry biomass increased from 2.22% to 4.41%, whereas the algae maintained a
      constant GLA to TFA ratio within the aeration rate tested. The dependence of GLA
      production on the aeration rate was explained by interrelating the GLA production
      rate with the specific growth rate using the Luedeking and Piret mixed growth
      model. 

PMID- 24031800
TI  - Production and characterization of tyrosinase activity in Pycnoporus sanguineus
      CCT-4518 Crude extract.
AB  - Tyrosinase is an enzyme of industrial interest. The production and
      characterization of tyrosinase from P. sanguineus CCT-4518 were investigated. The
      selection of inductors, luminosity influence, inoculum size and type of culture
      medium on the production of tyrosinase and the effect of inhibitors on enzyme
      activity were performed. Optimum conditions for intracellular tyrosinase
      production was observed after 2 days using 0.15% L-tyrosine as inducer, in the
      presence of light, with inoculum size of 10 mycelium discs, using 2% malt extract
      broth medium, incubated at 30 degrees C, and constant agitation of 150 rpm.
      Tyrosinase activity was completely inhibited by the addition of 6 mM
      salicylhydroxamic acid or phenylthiourea, however an inhibition of 4.15% was
      recorded by the addition of 0.1 mM sodium azide. No inhibition could be detected
      in case of 0.1 mM phenyl methanesulfonyl fluoride addition. Optimal conditions
      for intracellular tyrosinase activity using L-dopa as substrate were observed at
      pH 6.6 and 45 degrees C. Thermal stability studies indicated that the enzyme is
      stable at 45 degrees C for 15 minutes. Higher temperatures decreased tyrosinase
      activity. Enzyme production was confirmed by non-denaturing polyacrylamide gel
      electrophoresis and the protein profile was investigated by denaturing
      polyacrylamide gel electrophoresis. 

PMID- 24031801
TI  - Optimization of extracellular thermophilic highly alkaline lipase from
      thermophilic bacillus sp isolated from hotspring of Arunachal Pradesh, India.
AB  - Studies on lipase production were carried out with a bacterial strain (Bacillus
      sp LBN 2) isolated from soil sample of hotspring of Arunachal Pradesh, India. The
      cells were cultivated in a mineral medium with maximum production at 1% groundnut
      oil. The optimum temperature and initial medium pH for lipase production by the
      organism were 50(0)C and 9.0 respectively. The molecular mass was found to be
      33KDa by SDS PAGE. The optimal pH and temperature for activity were 10 and 60(0)C
      respectively. The enzyme was found to be stable in the pH range of 8-11 with 90%
      retention of activity at pH 11. The enzyme retained 90% activity at 60(0)C and
      70% of activity at 70(0)C for 1h. The lipase was found to be stable in acetone
      followed by ethanol. The present findings suggested the enzyme to be thermophilic
      alkaline lipase. 

PMID- 24031802
TI  - Production of Lytic Enzymes by Trichoderma Isolates during in vitro Antagonism
      with Aspergillus Niger, The Causal Agent of Collar ROT of Peanut.
AB  - Twelve isolates of Trichoderma (six of T. harzianum, five of T. viride, one of T.
      virens), which reduced variably the incidence of collar rot disease caused in
      peanut by Aspergillus niger Van Tieghem, were evaluated for their potential to
      produce lytic enzymes during in vitro antagonism. T. viride 60 inhibited highest
      (86.2%) growth of test fungus followed by T. harzianum 2J (80.4%) at 6 days after
      inoculation (DAI) on PDA media. The specific activities of chitinase, beta-1,3
      glucanase and protease were 11, 3.46 and 9 folds higher in T6 antagonist (T.
      viride 60 and A. niger interactions) followed by 8.72, 2.85 and 9 folds in
      T8antagonist (T. harzianum 2J and A. niger interactions), respectively, compared
      to the activity produced by control petri plate T13 (A. niger alone) at 6 DAI.
      Activity of these lytic enzymes induced in antagonists' plates comprises the
      growth of Trichoderma isolates. However, cellulase and poly galacturonase were
      found least amount in these antagonists treatment. A significant positive
      correlation (p=0.01) between percentage growth inhibition of test fungus and
      lytic enzymes - (chitinase, beta-1,3-glucanase and protease) in the culture
      medium of antagonist treatment established a relationship to inhibit growth of
      fungal pathogen by increasing the levels of these enzymes. Among the Trichoderma
      isolates, T. viride 60 was found best strain to be used in biological control of
      plant pathogen A. niger. 

PMID- 24031803
TI  - Alkali pretreated of wheat straw and its enzymatic hydrolysis.
AB  - The efficiency of enzymatic hydrolysis of cellulose can be improved by various
      pretreatments of the substrate. In order to increase the efficiency of enzymatic
      saccharification of the wheat straw, we determined the effect of different
      pretreatments on the physical structure, chemical components and enzymatic
      saccharification of wheat straw. Our results showed that combination of grinding
      and sodium hydroxide (NaOH) treatment had high effect on the enzymatic hydrolysis
      of wheat straws. The optimal pretreatment condition was to grind the wheat straws
      into the sizes of 120 meshes followed by treatment with 1.0% NaOH for 1.5 h (121
      degrees C/15psi). Under this condition, the cellulose content of wheat straw was
      increased by 44.52%, while the content of hemicellulose and lignin was decreased
      by 44.15% and 42.52%, respectively. Scanning Electronic Microscopy and infrared
      spectrum analyses showed that significant changes occurred in the structure of
      wheat straws after pretreatment, which is favorable for the hydrolysis and
      saccharification. Cellulase produced by Penicillium waksmanii F10-2 was used to
      hydrolyze the pretreated wheat straw and the optimal condition was determined to
      be 30 h of enzymatic reaction under the temperature of 55 degrees C, pH 5.5 and
      substrate concentration of 3%. 

PMID- 24031804
TI  - Production of inulinase from Kluyveromyces marxianus using dahlia tuber extract.
AB  - Various carbon sources were evaluated for production of inulinase by yeast,
      Kluyveromyces marxianus MTCC 3995. Highest inulinase activity was observed with
      Dahlia extract (25.3 nkat mL(-1)) as carbon source. The enzyme activity was 1.4
      folds higher than that observed in media containing pure chicory inulin (17.8
      nkat mL(-1)). The yeast showed good growth on a simple medium containing dahlia
      extract (20% w/v) and yeast extract (2%w/v) as carbon and nitrogen source
      respectively, in 96 h. at 28 degrees C and 120 rpm. Lowest inulinase yield (4.8
      nkat mL(-1)) was seen in the medium containing glucose as C-source. Although
      varied inulinase levels were noticed on different C- sources, Inulinase: Sucrase
      (I/S) ratios were noticed to be similar. Among various protein sources tested,
      yeast extract was found to be the best source followed by beef extract (17.9 nkat
      mL(-1)) and peptone (13.8 nkat mL(-1)). The enzyme was optimally active at pH
      (4.0) and 50 degrees C. TLC analysis of end product revealed that inulinase
      hydrolyzed inulin exclusively into fructose. Results suggest that the dahlia
      extract induced exoinulinase synthesis in Kluyveromyces marxianus and can be
      utilized as a potential substrate for inulinase production. 

PMID- 24031805
TI  - Biosynthesis, purification and characterization of endoglucanase from a xylanase
      producing strain Aspergillus niger B03.
AB  - An extracellular endoglucanase was isolated from the culture liquid of xylanase
      producing strain Aspergillus niger B03. The enzyme was purified to a homogenous
      form, using consecutive ultrafiltration, anion exchange chromatography, and gel
      filtration. Endoglucanase was a monomer protein with a molecular weight of 26,900
      Da determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and
      28,800 Da determined by gel filtration. The optimal pH and temperature values for
      the enzyme action were 3.5 and 65  degrees C respectively. Endoglucanase was
      stable at 40  degrees C, pH 3.0 for 210 min. The substrate specificity of the
      enzyme was determined with carboxymethyl cellulose, filter paper, and different
      glycosides. Endoglucanase displayed maximum activity in the case of carboxymethyl
      cellulose, with a Km value of 21.01 mg/mL. The substrate specificity and the
      pattern of substrate degradation suggested that the enzyme is an endoglucanase.
      Endoglucanase showed a synergism with endoxylanase in corn cobs hydrolysis. 

PMID- 24031806
TI  - Systematic mutagenesis method for enhanced production of bacitracin by Bacillus
      licheniformis Mutant Strain UV-MN-HN-6.
AB  - The purpose of the current study was intended to obtain the enhanced production
      of bacitracin by Bacillus licheniformis through random mutagenesis and
      optimization of various parameters. Several isolates of Bacillus licheniformis
      were isolated from local habitat and isolate designated as GP-35 produced maximum
      bacitracin production (14+/-0.72 IU ml(-1)). Bacitracin production of Bacillus
      licheniformis GP-35 was increased to 23+/-0.69 IU ml(-1) after treatment with
      ultraviolet (UV) radiations. Similarly, treatment of vegetative cells of GP-35
      with chemicals like N-methyl N'-nitro N-nitroso guanidine (MNNG) and Nitrous acid
      (HNO2) increased the bacitracin production to a level of 31+/-1.35 IU ml(-1) and
      27+/-0.89 IU ml(-1)respectively. Treatment of isolate GP-35 with combined effect
      of UV and chemical treatment yield significantly higher titers of bacitracin with
      maximum bacitracin production of 41.6+/-0.92 IU ml(-1). Production of bacitracin
      was further enhanced (59.1+/-1.35 IU ml(-1)) by optimization of different
      parameters like phosphate sources, organic acids as well as temperature and pH.
      An increase of 4.22 fold in the production of bacitracin after mutagenesis and
      optimization of various parameters was achieved in comparison to wild type.
      Mutant strain was highly stable and produced consistent yield of bacitracin even
      after 15 generations. On the basis of kinetic variables, notably Yp/s (IU/g
      substrate), Yp/x (IU/g cells), Yx/s(g/g), Yp/s, mutant strain B. licheniformis UV
      MN-HN-6 was found to be a hyperproducer of bacitracin. 

PMID- 24031807
TI  - Fermentation and enzyme treatments for sorghum.
AB  - Sorghum (Sorghum bicolor Moench) is the fifth most produced cereal worldwide.
      However, some varieties of this cereal contain antinutritional factors, such as
      tannins and phytate that may form stable complexes with proteins and minerals
      which decreases digestibility and nutritional value. The present study sought to
      diminish antinutritional tannins and phytate present in sorghum grains. Three
      different treatments were studied for that purpose, using enzymes tannase (945
      U/Kg sorghum), phytase (2640 U/Kg sorghum) and Paecilomyces variotii (1.6 X 10(7)
      spores/mL); A) Tannase, phytase and Paecilomyces variotii, during 5 and 10 days;
      B) An innovative blend made of tanase and phytase for 5 days followed by a Pv
      increase for 5 more days; C) a third treatment where the reversed order of B was
      used starting with Pv for 5 days and then the blend of tannase and phytase for 5
      more days. The results have shown that on average the three treatments were able
      to reduce total phenols and both hydrolysable and condensed tannins by 40.6,
      38.92 and 58.00 %, respectively. Phytase increased the amount of available
      inorganic phosphorous, on the average by 78.3 %. The most promising results
      concerning tannins and phytate decreases were obtained by the enzymes combination
      of tannase and phytase. The three treatments have shown effective on diminishing
      tannin and phytate contents in sorghum flour which leads us to affirm that the
      proposed treatments can be used to increase the nutritive value of sorghum grains
      destined for either animal feeds or human nutrition. 

PMID- 24031808
TI  - Seasonality of viral respiratory infections in southeast of Brazil: the influence
      of temperature and air humidity.
AB  - Viruses are the major cause of lower respiratory tract infections in childhood
      and the main viruses involved are Human Respiratory Syncytial Virus (HRSV), Human
      Metapneumovirus (HMPV), Influenzavirus A and B (FLUA and FLUB), Human
      Parainfluenza Virus 1, 2 and 3 (HPIV1, 2 and 3) and Human Rhinovirus (HRV). The
      purposes of this study were to detect respiratory viruses in hospitalized
      children younger than six years and identify the influence of temperature and
      relative air humidity on the detected viruses. Samples of nasopharyngeal washes
      were collected from hospitalized children between May/2004 and September/2005.
      Methods of viral detection were RT-PCR, PCR and HRV amplicons were confirmed by
      hybridization. Results showed 54% (148/272) of viral positivity. HRSV was
      detected in 29% (79/272) of the samples; HRV in 23.1% (63/272); HPIV3 in 5.1%
      (14/272); HMPV in 3.3% (9/272); HPIV1 in 2.9% (8/272); FLUB in 1.4% (4/272), FLUA
      in 1.1% (3/272), and HPIV2 in 0.3% (1/272). The highest detection rates occurred
      mainly in the spring 2004 and in the autumn 2005. It was observed that viral
      respiratory infections tend to increase as the relative air humidity decreases,
      showing significant association with monthly averages of minimal temperature and
      minimal relative air humidity. In conclusion, viral respiratory infections vary
      according to temperature and relative air humidity and viral respiratory
      infections present major incidences it coldest and driest periods. 

PMID- 24031809
TI  - Statistical optimisation of cell growth and carotenoid production by rhodotorula
      mucilaginosa.
AB  - Sequential statistical methods were used to maximise carotenoid production by a
      strain of Rhodotorula mucilaginosa, isolated from the Brazilian ecosystem.
      Initially, a factorial 2(5-1) experimental design was used, and the variables
      were pH and the levels of glucose, yeast extract, MgSO4.7H2O and KH2PO4. The
      nitrogen source (yeast extract) was the most important variable in enhancing
      carotenoid production; MgSO4.7H2O and KH2PO4 had a negative influence. The
      initial pH had no significant effect on carotenoid and cell productions. We
      further investigated the effects of glucose and yeast extract effects, using a
      second-order central composite design (CCD) to optimise carotenoid production,
      which was adequately approximated with a full quadratic equation obtained from a
      two-factor-2-level design. The analysis of quadratic surfaces showed that after 5
      days of cultivation at 25  degrees C, the maximum carotenoid concentration (745
      ug l(-1)) was obtained with 15 g l(-1) of yeast extract and 20 g l(-1) of
      glucose. The maximum carotenoid production (152 ug g(-1)) was obtained with 5 g
      l(-1) yeast extract and 10 g l(-1) glucose. Carotenoid formation was more
      sensitive to changes in yeast extract concentration than to changes in glucose
      concentration. Maximum cell production was achieved with 15-17 g l(-1) of yeast
      extract and 15-20 g l(-1) of glucose. 

PMID- 24031810
TI  - Biosurfactants production by yeasts using soybean oil and glycerol as low cost
      substrate.
AB  - Biosurfactants are bioactive agents that can be produced by many different
      microorganisms. Among those, special attention is given to yeasts, since they can
      produce many types of biosurfactants in large scale, using several kinds of
      substrates, justifying its use for industrial production of those products. For
      this production to be economically viable, the use of residual carbon sources is
      recommended. The present study isolated yeasts from soil contaminated with
      petroleum oil hydrocarbons and assessed their capacity for producing
      biosurfactants in low cost substrates. From a microbial consortium enriched,
      seven yeasts were isolated, all showing potential for producing biosurfactants in
      soybean oil. The isolate LBPF 3, characterized as Candida antarctica, obtained
      the highest levels of production - with a final production of 13.86 g/L. The
      isolate LBPF 9, using glycerol carbon source, obtained the highest reduction in
      surface tension in the growth medium: approximately 43% of reduction after 24
      hours of incubation. The products obtained by the isolates presented surfactant
      activity, which reduced water surface tension to values that varied from 34 mN/m,
      obtained from the product of isolates LBPF 3 and 16 LBPF 7 (respectively
      characterized as Candida antarctica and Candida albicans) to 43 mN/m from the
      isolate LPPF 9, using glycerol as substrate. The assessed isolates all showed
      potential for the production of biosurfactants in conventional sources of carbon
      as well as in agroindustrial residue, especially in glycerol. 

PMID- 24031811
TI  - Evaluation of biomass production, carotenoid level and antioxidant capacity
      produced by Thermus filiformis Using fractional factorial design.
AB  - A fractional factorial design 2(5-1) was used to evaluate the effect of
      temperature, pH, and concentrations of yeast extract, tryptone and Nitsch's trace
      elements on the biomass, total carotenoids and protection against singlet oxygen
      by carotenoid extracts of the bacterium Thermus filiformis. In addition, the
      carotenoid composition was determined by high-performance liquid chromatography
      connected to a diode array and mass spectrometer detectors (HPLC-DAD-MS/MS). The
      production of biomass ranged from 0.113 to 0.658 g/L, the total carotenoid from
      137.6 to 1,517.4 ug/g and the protection against singlet oxygen from 4.3 to 85.1
      %. Results of the fractional factorial design showed that temperature had a
      negative effect on biomass production and a positive effect on carotenoid content
      and protection against singlet oxygen, besides, high levels of pH value,
      concentrations of yeast extract and tryptone had a positive effect on biomass
      production only at lower temperatures. The main carotenoids of T. filiformis were
      thermozeaxanthins. In the tested conditions, changes in the levels of the
      variables influenced the biomass, carotenoid production, and protection against
      singlet oxygen, although they did not influence the carotenoid profile. The
      results of this study provide a better understanding on the interactions among
      certain nutritional and cultivation conditions of a thermophile bacterium,
      Thermus filiformis, on biomass and carotenoid amounts, as well as on the
      antioxidant capacity. 

PMID- 24031812
TI  - Molecular characterisation and biomass and metabolite production of Lactobacillus
      reuteri LPB P01-001: A potential probiotic.
AB  - Lactobacillus reuteri LPB P01-001 was isolated from the gastrointestinal tract of
      wild swine and was characterised by biochemical testing and sequencing of gene
      16S rRNA. A simple and low-cost culture medium based on cane sugar (2.5% p/v) and
      yeast extract (1% p/v) was used in the production of this probiotic. The
      fermentative conditions were a) pH control at 6.5 and b) no pH control; both were
      set at 37 degrees C in a 12 L slightly stirred tank bioreactor. Fermentation
      parameters such as the specific growth rate, productivity and yield of biomass,
      lactic and acetic acid levels were determined. L. reuteri LPB P01-001 behaves as
      an aciduric bacteria because it grows better in a low pH medium without pH
      control. However, the lactic acid production yield was practically half (9.22
      g.L(-1)) of that obtained under a constant pH of 6.5, which reached 30.5 g.L(-1)
      after 28 hours of fermentation. The acetic acid production was also higher under
      pH-controlled fermentation, reaching 10.09 g.L(-1)after 28 hours of fermentation.
      These parameters may raise the interest of those committed to the efficient
      production of a probiotic agent for swine. 

PMID- 24031813
TI  - Screening and characterization of a novel alkaline lipase from Acinetobacter
      calcoaceticus 1-7 Isolated from bohai bay in china for detergent formulation.
AB  - A novel alkaline lipase-producing strain 1-7 identified as Acinetobacter
      calcoaceticus was isolated from soil samples collected from Bohai Bay, China,
      using an olive oil alkaline plate, which contained olive oil as the sole carbon
      source. The lipase from strain 1-7 showed the maximum activity at pH 9.0 under 40
      degrees C. One interesting feature of this enzyme is that it exhibits lipase
      activity over a broad range of temperatures and good stability. It is also stable
      at a broad range of pHs from 4.0 to 10.0 for 24 h. Its catalytic activity was
      highly enhanced in the presence of Ca(2+), Mg(2+) and K(+), but partially
      inhibited by Cu(2+), Al(3+), Fe(3+), Ba(2+)and Zn(2+). The fact that it displays
      marked stability and activity in the presence of TritonX-100, Tween-20, Tween-80,
      SDS, Hydrogen peroxide, Sodium perborate, Sodium hypochlorite, Sodium citrate,
      Sodium taurocholate, Glycerine and NaCl suggests that this lipase is suitable as
      an additive in detergent formulations. 

PMID- 24031814
TI  - Osmo-, Thermo- and Ethanol- Tolerances of Saccharomyces cerevisiae S1.
AB  - Saccharomyces cerevisiae S1, which is a locally isolated and improved strain
      showed viability at 40, 45 and 50 degrees C and produced ethanol at 40, 43 and 45
      degrees C. When the cells were given heat shock at 45 degrees C for 30min and
      grown at 40 degrees C, 100% viability was observed for 60h, and addition of
      200gL(-1) ethanol has led to complete cell death at 30h. Heat shock given at 45
      degrees C (for 30min) has improved the tolerance to temperature induced ethanol
      shock leading to 37% viability at 30h. When the cells were subjected to ethanol
      (200gL(-1) for 30 min) and osmotic shock (sorbitol 300gL(-1)), trehalose contents
      in the cells were increased. The heat shocked cells showed better viability in
      presence of added ethanol. Soy flour supplementation has improved the viability
      of S. cerevisiae S1 to 80% in presence of 100gL(-1) added ethanol and to 60% in
      presence of 300gL(-1)sorbitol. In presence of sorbitol (200gL(-1)) and ethanol
      (50gL(-1)) at 40 degrees C, 46% viability was retained by S. cerevisiae S1 at 48h
      and it was improved to 80% by soy flour supplementation. 

PMID- 24031815
TI  - Influence of phenolic compounds on the growth and arginine deiminase system in a
      wine lactic acid bacterium.
AB  - The influence of seven phenolic compounds, normally present in wine, on the
      growth and arginine deiminase system (ADI) of Lactobacillus hilgardii X1B, a wine
      lactic acid bacterium, was established. This system provides energy for bacterial
      growth and produces citrulline that reacts with ethanol forming the carcinogen
      ethyl carbamate (EC), found in some wines. The influence of phenolic compounds on
      bacterial growth was compound dependent. Growth and final pH values increased in
      presence of arginine. Arginine consumption decreased in presence of
      protocatechuic and gallic acids (31 and 17%, respectively) and increased in
      presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic
      acids (between 10 and 13%, respectively). ADI enzyme activities varied in
      presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids
      stimulated the enzyme arginine deiminase about 37-40%. Amounts of 200 mg/L gallic
      and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and
      100%, respectively. Ornithine transcarbamylase activity was not modified at all
      concentrations of phenolic compounds. As gallic and protocatechuic acids
      inhibited the arginine deiminase enzyme that produces citrulline, precursor of
      EC, these results are important considering the formation of toxic compounds. 

PMID- 24031816
TI  - Optimization of nutrition factors on chitinase production from a newly isolated
      Chitiolyticbacter meiyuanensis SYBC-H1.
AB  - The present study reports statistical medial optimization for chitinase
      production by a novel bacterial strain isolated from soil recently, which the
      name Chitinolyticbacter meiyuanensis SYBC-H1 is proposed. A sequential
      statistical methodology comprising of Plackett-Burman and response surface
      methodology (RSM) was applied to enhance the fermentative production of
      chitinase, in which inulin was firstly used as an effective carbon source. As a
      result, maximum chitinase activity of 5.17 U/mL was obtained in the optimized
      medium, which was 15.5-fold higher than that in the basal medium. The triplicate
      verification experiments were performed under the optimized nutrients levels
      which indicated that it well agreed with the predicted value. 

PMID- 24031817
TI  - Growth, fatty acid profile in major lipid classes and lipid fluidity of
      Aurantiochytrium mangrovei SK-02 As a function of growth temperature.
AB  - Aurantiochytrium mangrovei Sk-02 was grown in a medium containing glucose (40
      g/l), yeast extract (10 g/L) and sea salts (15 g/L) at temperatures ranging from
      12 to 35 degrees C. The fastest growth (umax= 0.15 h(-1)) and highest fatty acid
      content of 415 mg/g-dry cell weight were found in the cells grown at 30 degrees
      C. However, the cells grown at 12 degrees C showed the highest percentage of
      polyunsaturated fatty acid (PUFA) (48.6% of total fatty acid). The percentage of
      docosahexaenoic acid (DHA) and pentadecanoic acid (C15:0) decreased with an
      increase in the growth temperature, whereas, palmitic acid (C16:0), stearic acid
      (C18:0) and DPA (C22:5n6) increased with an increase in the growth temperature.
      The composition of the major lipid class (%w/w) was slightly affected by the
      growth temperature. The fluidity of the organelle membrane or intracellular lipid
      (by DPH measurement) decreased with an increase in the growth temperatures, while
      the plasma membrane fluidity (by TMA-DPH measurement) could still maintain its
      fluidity in a wide range of temperatures (15 - 37 degrees C). Furthermore, the
      distribution of DHA was found to be higher (36 - 54%) in phospholipid (PL) as
      compared to neutral lipid (NL) (20 - 41%). 

PMID- 24031818
TI  - Thermostability of xylanolytic enzymes produced by Lentinula edodes UFV70.
AB  - Xylanolytic enzymes produced by Lentinula edodes UFV70, cultivated in eucalyptus
      sawdust/rice bran medium, were stable at 50, 60 and 65 degrees C for 21 hours,
      losing only 15-25% activity. Fungus incubation at 50 degrees C for 12 hours and
      at 65 degrees C for 24 hours increased the amount of xylose produced. 

PMID- 24031819
TI  - Screening of actinomycetes from earthworm castings for their antimicrobial
      activity and industrial enzymes.
AB  - Actinomycetes from earthworm castings were isolated and screened for their
      antimicrobial activity and industrial enzymes. A total of 48 isolates were
      obtained from 12 samples of earthworm castings. Highest numbers of isolates were
      recovered from forest site (58.33 %) as compared to grassland (25%) and
      agricultural land (16.66%). The growth patterns, mycelial coloration of abundance
      actinomycetes were documented. The dominant genera Identified by cultural,
      morphological and physiological characteristics were Streptomyces (60.41%)
      followed by Streptosporangium (10.41%),Saccharopolyspora (6.25%) and Nocardia
      (6.25%). Besides these, other genera like Micromonospora, Actinomadura,
      Microbispora, Planobispora and Nocardiopsis were also recovered but in low
      frequency. Among the 48 isolates, 52.08% were found active against one or more
      test organisms. Out of 25 active isolates 16% showed activity against bacterial,
      human fungal as well as phytopathogens. Among 48 isolates 38, 32, 21, 20, 16 and
      14 produced enzyme amylase, caseinase, cellulase, gelatinase, xylanase and lipase
      respectively while 10 isolates produced all the enzymes. More interestingly 2, 3,
      and 1 isolates produced amylase, xylanase and lipase at 45 degrees C
      respectively. In the view of its antimicrobial activity as well as enzyme
      production capability the genus Streptomyces was dominant. The isolate EWC 7(2)
      was most promising on the basis of its interesting antimicrobial activity and was
      identified as Streptomyces rochei. The results of these findings have increased
      the scope of finding industrially important actinomycetes from earthworm castings
      and these organisms could be promising sources for industrially important
      molecules or enzymes. 

PMID- 24031820
TI  - Clinical importance and representation of toxigenic and non-toxigenic Clostridium
      difficile cultivated from stool samples of hospitalized patients.
AB  - The aim of this study was to fortify the clinical importance and representation
      of toxigenic and non-toxigenic Clostridium difficile isolated from stool samples
      of hospitalized patients. This survey included 80 hospitalized patients with
      diarrhea and positive findings of Clostridium difficile in stool samples, and 100
      hospitalized patients with formed stool as a control group. Bacteriological
      examination of a stool samples was conducted using standard microbiological
      methods. Stool sample were inoculated directly on nutrient media for bacterial
      cultivation (blood agar using 5% sheep blood, Endo agar, selective Salmonella
      Shigella agar, Selenite-F broth, CIN agar and Skirrow's medium), and to selective
      cycloserine-cefoxitin-fructose agar (CCFA) (Biomedics, Parg qe tehnicologico,
      Madrid, Spain) for isolation of Clostridium difficile. Clostridium difficile
      toxin was detected by ELISA-ridascreen Clostridium difficile Toxin A/B (R
      Biopharm AG, Germany) and ColorPAC ToxinA test (Becton Dickinson, USA).
      Examination of stool specimens for the presence of parasites (causing diarrhea)
      was done using standard methods (conventional microscopy), commercial
      concentration test Paraprep S Gold kit (Dia Mondial, France) and RIDA((r))QUICK
      Cryptosporidium/Giardia Combi test (R-Biopharm AG, Germany). Examination of stool
      specimens for the presence of fungi (causing diarrhea) was performed by standard
      methods. All stool samples positive for Clostridium difficile were tested for
      Rota, Noro, Astro and Adeno viruses by ELISA - ridascreen (R-Biopharm AG,
      Germany). In this research we isolated 99 Clostridium difficile strains from 116
      stool samples of 80 hospitalized patients with diarrhea. The 53 (66.25%) of
      patients with diarrhea were positive for toxins A and B, one (1.25%) were
      positive for only toxin B. Non-toxigenic Clostridium difficile isolated from
      samples of 26 (32.5%) patients. However, other pathogenic microorganisms of
      intestinal tract cultivated from samples of 16 patients. Examination of
      cultivated colonies revealed that most of cultivated species belonged to genera
      of Campylobacter spp., Salmonella spp., and Candida spp.. In control group,
      toxigenic Clostridium difficile cultivated from stool samples of two patients
      (2%) and non-toxigenic Clostridium difficile from samples of five patients (5%).
      This research confirmed clinical importance of toxigenic Clostridium difficile
      found in liquid stool samples of hospitalized patient, and the possibility of
      asymptomatic carriage in 2% of patients with formed stool. 

PMID- 24031821
TI  - Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata.
AB  - Our purpose was to determine the anti-Mycobacterium tuberculosis activity of the
      metabolites produced by the endophitic fungus Phomopsis stipata (Lib.) B. Sutton,
      (Diaporthaceae), cultivated in different media. The antimycobacterial activity
      was assessed through the Resazurin Microtiter Assay (REMA) and the cytotoxicity
      test performed on macrophage cell line. The extracts derived from fungi grown on
      Corn Medium and Potato Dextrose Broth presented the smallest values of Minimum
      Inhibitory Concentration (MIC) and low cytotoxicity, which implies a high
      selectivity index. This is the first report on the chemical composition and
      antitubercular activity of metabolites of P. stipata, as well as the influence of
      culture medium on these properties. 

PMID- 24031822
TI  - Multiple organ dysfunction syndrome associated with Mycoplasma pneumoniae
      infection.
AB  - In this study, we report one case of a three-year-old boy infected with
      Mycoplasma pneumonia (MP) and presenting concomitant multiple organ damage of the
      heart, kidney, lung and liver, among others, together with a brief review for the
      diagnosis and treatment of MP infection with multiple organ dysfunction syndrome
      (MODS). 

PMID- 24031823
TI  - Farnesol in combination with N-acetylcysteine against Staphylococcus epidermidis
      planktonic and biofilm cells.
AB  - Staphylococcus epidermidis is the most frequent cause of nosocomial sepsis and
      catheter-related infections, in which biofilm formation is considered to be the
      main virulence mechanism. In biofilm environment, microbes exhibit enhanced
      resistance to antimicrobial agents. This fact boosted the search of possible
      alternatives to antibiotics. Farnesol and N-acetylcysteine (NAC) are non
      antibiotic drugs that have demonstrated antibacterial properties. In this study,
      the effect of farnesol and NAC isolated or in combination (farnesol+NAC) was
      evaluated. NAC at 10 * MIC caused a total cell death in planktonic cells. On the
      other hand, S. epidermidis biofilms exhibited 4 log reduction in viable cell
      number after a 24h treatment with NAC at the former concentration. Our results
      demonstrated that there was a higher CFU log reduction of S. epidermidis
      planktonic cells when farnesol was combined with NAC at 1 * MIC relatively to
      each agent alone. However, these results were not relevant because NAC alone at
      10 * MIC was always the condition which gave the best results, having a very high
      killing effect on planktonic cells and a significant bactericidal effect on
      biofilm cells. This study demonstrated that no synergy was observed between
      farnesol and NAC. However, the pronounced antibacterial effect of NAC against S.
      epidermidis, on both lifestyles, indicates the use of NAC as a potential
      therapeutic agent in alternative to antibiotics. 

PMID- 24031824
TI  - First occurrence of bla OXA-58 in Acinetobacter baumannii isolated from a
      clinical sample in Southern Brazil.
AB  - This is the first report of an Acinetobacter baumannii from clinical origin
      carrying the bla OXA-58 gene in Brazil. The isolate included in this study was
      from a patient during an outbreak in Porto Alegre, RS, Southern Brazil, in 2007.
      It was resistant to most of the beta-lactams tested, it has also the bla OXA-65
      gene and the ISAbal sequence located upstream to both bla OXA genes detected and
      it has a MIC of imipenem of 64 MUg/mL. 

PMID- 24031825
TI  - Rodentborne fungal pathogens in wetland agroecosystem.
AB  - The past few decades have witnessed an overwhelming increase in the incidence of
      fungal infections, particularly in immunocompromised individuals. Consequently,
      zoonotic diseases, especially through rodents constitute a prominent group among
      the emerging diseases. Rodents are commensal to man and related health risks are
      common. Water rats (Rattus norvegicus) are typical to Vembanadu-Kol wetland
      agroecosystems, where they can act as a good carrier nexus for pathogens. The
      present study evaluates the carrier status of water rats with respect to fungal
      pathogens. A total of fifty two fungi covering eighteen families were isolated.
      Among the isolates, eight were dermaptophytes and Chrysosporium sp. (89.18%) was
      the frequent isolate. The source-wise analyses showed an increased isolation from
      ventral hair (67 isolates). Water rats of Vembanadu-Kol wetland agroecosystem are
      potent carrier of dermaptophytes and other opportunistic fungi, and strong
      carrier paths are existing too. 

PMID- 24031826
TI  - A combined enrichment/polymerase chain reaction based method for the routine
      screening of Streptococcus agalactiae in pregnant women.
AB  - Group B Streptococcus (GBS) is the most common cause of life-threatening
      infection in neonates. Guidelines from CDC recommend universal screening of
      pregnant women for rectovaginal GBS colonization. The objective of this study was
      to compare the performance of a combined enrichment/PCR based method targeting
      the atr gene in relation to culture using enrichment with selective broth medium
      (standard method) to identify the presence of GBS in pregnant women. Rectovaginal
      GBS samples from women at >=36 weeks of pregnancy were obtained with a swab and
      analyzed by the two methods. A total of 89 samples were evaluated. The prevalence
      of positive results for GBS detection was considerable higher when assessed by
      the combined enrichment/PCR method than with the standard method (35.9% versus
      22.5%, respectively). The results demonstrated that the use of selective
      enrichment broth followed by PCR targeting the atr gene is a highly sensitive,
      specific and accurate test for GBS screening in pregnant women, allowing the
      detection of the bacteria even in lightly colonized patients. This PCR
      methodology may provide a useful diagnostic tool for GBS detection and
      contributes for a more accurate and effective intrapartum antibiotic and lower
      newborn mortality and morbidity. 

PMID- 24031827
TI  - Diagnosis of the pulmonary tuberculosis by polymerase chain reaction: a
      comparative study between HIV-positive and -negative individuals.
AB  - This study was performed to assess the efficiency of polymerase chain reaction
      (PCR) directly from sputum for the diagnosis of pulmonary tuberculosis by
      comparison between HIV-positive and HIV-negative individuals. Sputum samples were
      collected from hospitalized patients admitted with a clinical diagnosis of
      pulmonary tuberculosis, and subjected to smear microscopy, culture on LJ medium
      and detection of M. tuberculosis by PCR. Sensitivity, specificity, and predictive
      values (positive and negative) were calculated using smear and/or culture at day
      42 as the gold standard, by comparing the yield in HIV-positive and HIV-negative
      individuals. Regardless of serostatus, the technique's yield had 62% sensitivity,
      70% specificity, 79% positive predictive value, 50% negative predictive value,
      and 65% accuracy. HIV-negative had 64% sensitivity, 74% specificity, 75% positive
      predictive value, 63% negative predictive value, and 68% accuracy. HIV-positive
      had 59% sensitivity, 33% specificity, 87% positive predictive value, 10% negative
      predictive value, and 56% accuracy. The PCR showed a higher yield in HIV-negative
      individuals compared to HIV-positive individuals. 

PMID- 24031828
TI  - Susceptibility tests of oropharyngeal Candida albicans from egyptian patients to
      fluconazole determined by three methods.
AB  - Candida albicans frequently cause oropharyngeal candidiasis in immunocompromised
      patients. As some of these isolates show resistance against azoles, the clinician
      is wary of initiating therapy with fluconazole (FZ) until a final susceptibility
      report is generated. We aimed to evaluate the efficacy of rapid flow cytometry
      (FCM) and disc diffusion (DD) methods in comparison to reference microdilution
      (MD) of Clinical and Laboratory Standards Institute (CLSI) method for FZ. Thirty
      seven Candida albicans isolates were tested by the three methods. By both MD and
      FCM, 26/37 (70.3%) were sensitive with minimal inhibitory concentration (MIC) <=
      8MUg/ml, 5/37 (13.5%) were susceptible dose dependant (S-DD) with MIC 16-32
      MUg/ml and 6/37 (16.2%) were resistant with MIC >=64MUg/ml. More than 92% of
      isolates susceptible to FZ by the MD were susceptible by the DD methods with good
      agreement (81.08%, P = 0.000). However, 4/5 isolates diagnosed as S-DD by MD were
      resistant by DD. Interestingly, the MIC by FCM at 4 h showed excellent agreement
      (95.59%, P = 0.000) to that obtained by MD method at 24 h. Overall, FCM
      antifungal susceptibility testing provided rapid, reproducible results that are
      valuable alternative to MD. The DD test is recommended as a simple and reliable
      screening test for the detection of susceptible Candida albicans isolates to FZ. 

PMID- 24031829
TI  - Phenotypic and genotypic diversity of Pseudomonas aeruginosa strains isolated
      from hospitals in siedlce (Poland).
AB  - A total of 62 Pseudomonas aeruginosa strains isolated from two hospitals in
      Siedlce (Poland) were studied by repetitive element based PCR (rep-PCR) using BOX
      primer. BOX-PCR results revealed the presence of 7 numerous genotypes and 31
      unique patterns among isolates. Generally, the strains of P. aeruginosa were
      characterized by resistance to many antibiotics tested and by differences in
      serogroups and types of growth on cetrimide agar medium. However, the P.
      aeruginosa strains isolated from faeces showed much lower phenotypic and
      genotypic variations in comparison with strains obtained from other clinical
      specimens. It was observed that genetic techniques supported by phenotypic tests
      have enabled to conduct a detailed characterization of P. aeruginosa strains
      isolated from a particular environment at a particular time. 

PMID- 24031830
TI  - 16S rRNA gene-based identification of bacteria in postoperative endophthalmitis
      by PCR-Denaturing Gradient Gel Electrophoresis (PCR-DGGE) fingerprinting.
AB  - Conventional microbiological culture techniques are frequently insufficient to
      confirm endophthalmitis clinical cases which could require urgent medical
      attention because it could lead to permanent vision loss. We are proposing PCR
      DGGE and 16S rRNA gene libraries as an alternative to improve the detection and
      identification rate of bacterial species from endophthalmitis cases. 

PMID- 24031831
TI  - Microbiological biodiversity in poultry and paddy straw wastes in composting
      systems.
AB  - Immense quantity of waste is generated in association with poultry meat egg and
      crop production. The potential risks due to disposal of these wastes are
      magnified as a result of dense refinement of poultry production and the
      decreasing amount of land available for waste disposal. The study aims at
      studying the microbiological biodiversity of poultry waste and paddy straw based
      co-composting system. The predominant microflora of the poultry manure were
      bacteria, fungi, enteric bacteria and spore forming bacteria whose population was
      high at the initiation of composting but decreased significantly as the compost
      approached maturity. The initial load of inherent enteric groups of bacteria in
      poultry waste, that also includes some pathogenic ones, is considerably reduced
      and some new vital groups contributed to compost quality as the microbiological
      biodiversity sets in the system and becomes stable. Major fraction of nitrogen of
      poultry waste was subjected to ammonia volatilization and a fraction of it
      conserved by co-composting it in conjunction with wastes having low nitrogen
      contents. In the treatment T1 and T5, where poultry manure and paddy straws alone
      were composted, 60 and 30 percent of organic carbon, respectively, was lost over
      a period of six months. Whereas in treatments T2,T3 and T4, poultry manure and
      paddy straw were co-composted in the ratio of 3:1, 2:2 and 1:3, respectively,
      51.4,45.0 and 37.0 percent of carbon, respectively, was lost during
      decomposition. The C: N ratio in all the treatments decreased significantly to
      18.3 for T1, 24.7 for T2, 27.0 for T3, 34.9 for T4 and 38.5 for T5 at the end of
      composting period. 

PMID- 24031832
TI  - Biological control of rice brown spot with native isolates of three Trichoderma
      species.
AB  - Brown spot caused by Bipolaris oryzae is an important rice disease in Southern
      coast of Caspian Sea, the major rice growing region in Iran. A total of 45
      Trichoderma isolates were obtained from rice paddy fields in Golestan and
      Mazandaran provinces which belonged to Trichoderma harzianum, T. virens and T.
      atroviride species. Initially, they were screened against B. oryzae by antagonism
      tests including dual culture, volatile and nonvolatile metabolites and
      hyperparasitism. Results showed that Trichoderma isolates can significantly
      inhibit mycelium growth of pathogen in vitro by producing volatile and
      nonvolatile metabolites Light microscopic observations showed no evidence of
      mycoparasitic behaviour of the tested isolates of Trichoderma spp. such as
      coiling around the B. oryzae. According to in vitro experiments, Trichoderma
      isolates were selected in order to evaluate their efficacy in controlling brown
      spot in glasshouse using seed treatment and foliar spray methods. Concerning the
      glasshouse tests, two strains of T. harzianum significantly controlled the
      disease and one strain of T. atroviride increased the seedling growth. It is the
      first time that the biological control of rice brown spot and increase of
      seedling growth with Trichoderma species have been studied in Iran. 

PMID- 24031833
TI  - Occurrence of white rust (Albugo ipomoeae-panduratae) on Ipomoea acuminate In the
      brazilian mid-west.
AB  - Spontaneous plants of Ipomoea acuminata ("morning glory") exhibiting white rust
      pustules were found in a field crop area of Planaltina, DF, in the fall season of
      2010 and the disease causal agent was identified as Albugo ipomoea-panduratae
      (Oomycota). No reports of the association between A. ipomoea-panduratae and I.
      acuminata were known in Brazil previously to 2010. A reference specimen was
      deposited at the University of Brasilia Mycological Reference Collection. 

PMID- 24031834
TI  - The genetic diversity of genus Bacillus and the related genera revealed by 16s
      rRNA gene sequences and ardra analyses isolated from geothermal regions of
      turkey.
AB  - Previously isolated 115 endospore-forming bacilli were basically grouped
      according to their temperature requirements for growth: the thermophiles (74%),
      the facultative thermophiles (14%) and the mesophiles (12%). These isolates were
      taken into 16S rRNA gene sequence analyses, and they were clustered among the 7
      genera: Anoxybacillus, Aeribacillus, Bacillus, Brevibacillus, Geobacillus,
      Paenibacillus, and Thermoactinomycetes. Of these bacilli, only the thirty two
      isolates belonging to genera Bacillus (16), Brevibacillus (13), Paenibacillus (1)
      and Thermoactinomycetes (2) were selected and presented in this paper. The
      comparative sequence analyses revealed that the similarity values were ranged as
      91.4-100 %, 91.8- 99.2 %, 92.6- 99.8 % and 90.7 - 99.8 % between the isolates and
      the related type strains from these four genera, respectively. Twenty nine of
      them were found to be related with the validly published type strains. The most
      abundant species was B. thermoruber with 9 isolates followed by B. pumilus (6),
      B. lichenformis (3), B. subtilis (3), B. agri (3), B. smithii (2), T. vulgaris
      (2) and finally P. barengoltzii (1). In addition, isolates of A391a, B51a and
      D295 were proposed as novel species as their 16S rRNA gene sequences displayed
      similarities <= 97% to their closely related type strains. The AluI-, HaeIII- and
      TaqI-ARDRA results were in congruence with the 16S rRNA gene sequence analyses.
      The ARDRA results allowed us to differentiate these isolates, and their
      discriminative restriction fragments were able to be determined. Some of their
      phenotypic characters and their amylase, chitinase and protease production were
      also studied and biotechnologically valuable enzyme producing isolates were
      introduced in order to use in further studies. 

PMID- 24031835
TI  - Winter prevalence of obligate aphid pathogen Pandora neoaphidis mycosis in the
      host Myzus persicae populations in southern China: modeling description and
      biocontrol implication.
AB  - Pandora neoaphidis overwintering had been investigated by monitoring its
      prevalence in Myzus persicae populations in open fields. Cabbage plants in field
      plots were weekly taken after mycosis initiation, to count and examine the living
      and dead aphids infected by P. neoaphidis . Based on the field data, infection
      levels ( I) varied with field temperature (T), relative humidity (RH) and aphid
      count (numbers of living aphids per plant, N) over days ( D), fitting well to the
      modified logistic equation I =0.91/[1+exp(8.5+(2.0 H T H RH-20.2 NI 0) D)] ( r
      (2)=0.897), where H T indicated daily hours of low temperature (<4 degrees C), H
      RH daily hours of high air humidity (>90% RH) and I 0 primary infection level.
      The model demonstrated the abiotic and biotic factors influencing P. neoaphidis
      mycosis development in winter, and also verifies the fungal overwintering by
      infecting available host aphids without a resting stage. Ultimately, P.
      neoaphidis mycosis reduced 81.4% of aphid populations, presenting great potential
      for biocontrol. 

PMID- 24031836
TI  - Growth and enzymatic responses of phytopathogenic fungi to glucose in culture
      media and soil.
AB  - The effect of inoculation of Aspergillus flavus , Fusarium verticillioides , and
      Penicillium sp. in Dystrophic Red Latosol (DRL) and Eutroferric Red Latosol (ERL)
      soils with or without glucose on the total carbohydrate content and the
      dehydrogenase and amylase activities was studied. The fungal growth and spore
      production in culture medium with and without glucose were also evaluated. A
      completely randomized design with factorial arrangement was used. The addition of
      glucose in the culture medium increased the growth rate of A. flavus and
      Penicillium sp. but not of F. verticillioides . The number of spores increased
      1.2 for F. verticillioides and 8.2 times for A. flavus in the medium with
      glucose, but was reduced 3.5 times for Penicillium sp. The total carbohydrates
      contents reduced significantly according to first and second degree equations.
      The consumption of total carbohydrates by A. flavus and Penicillium sp. was
      higher than the control or soil inoculated with F. verticillioides . The addition
      of glucose to soils benefited the use of carbohydrates, probably due to the
      stimulation of fungal growth. Dehydrogenase activity increased between 1.5 to 1.8
      times ( p <0.05) in soils with glucose and inoculated with the fungi (except F.
      verticillioides ), in relation to soil without glucose. Amylase activity
      increased 1.3 to 1.5 times due to the addition of glucose in the soil. Increased
      amylase activity was observed in the DRL soil with glucose and inoculated with A.
      flavus and Penicillium sp. when compared to control. 

PMID- 24031837
TI  - Measuring bacterial cells size with AFM.
AB  - Atomic Force Microscopy (AFM) can be used to obtain high-resolution topographical
      images of bacteria revealing surface details and cell integrity. During scanning
      however, the interactions between the AFM probe and the membrane results in
      distortion of the images. Such distortions or artifacts are the result of
      geometrical effects related to bacterial cell height, specimen curvature and the
      AFM probe geometry. The most common artifact in imaging is surface broadening,
      what can lead to errors in bacterial sizing. Several methods of correction have
      been proposed to compensate for these artifacts and in this study we describe a
      simple geometric model for the interaction between the tip (a pyramidal shaped
      AFM probe) and the bacterium (Escherichia coli JM-109 strain) to minimize the
      enlarging effect. Approaches to bacteria immobilization and examples of AFM
      images analysis are also described. 

PMID- 24031838
TI  - Statistical evaluation of nutritional components impacting phycocyanin production
      Synechocystis SP.
AB  - Alkaliphilic cyanobacterial cultures were isolated from Lonar lake (MS, India).
      Among the set of cultures, Synechocystis sp, was studied for phycocyanin
      production. A maximum yield was obtained in BG-11 medium at optimized conditions
      (pH 10 and 16 h light). In order to increase the phycocyanin yield media
      optimization based on the eight media components a Plackett-Burman design of the
      12 experimental trials was used. As per the analysis CaCl2, 2H2O and Na2CO3 have
      been found to be the most influencing media components at 95% significance.
      Further the optimum concentrations of these components were estimated following a
      Box Wilson Central Composite Design (CCD) with four star points and five
      replicates at the center points for each of two factors was adopted for
      optimization of these two media components. The results indicated that there was
      an interlinked influence of CaCl2, 2H2O and Na2CO3 on 98% significance. The
      maximum yield of phycocyanin (12% of dry wt) could be obtained at 0.058 g/l and
      0.115 g/l of CaCl2, 2H2O and Na2CO3, respectively. 

PMID- 24031839
TI  - Characterization and lytic activity of Pseudomonas fluorescens phages from
      sewage.
AB  - Pseudomonas fluorescens phages from sewage were tested against P. fluorescens
      isolates of soil and sewage. The phages were characterized as to host range,
      morphology, structural proteins and genome fingerprint. Of the seven phages
      isolated, one was found to be abundant in sewage (5.9*10(7) pfu/mL), having broad
      host range, and distinct protein and DNA profile when compared to the other six
      phages. DNA restriction and protein profiles of the phages and their morphology
      indicate the diversity in the sewage environment. None of the isolates from the
      rhizosphere regions of various cultivated soils were susceptible to phages
      isolated from sewage. 

PMID- 24031840
TI  - Assessment of immunity against avian colibacillosis induced by an aroA mutant
      containing increased serum survival gene in broilers.
AB  - Colibacillosis is an important disease in the poultry industry which causes
      serious economic damages. As it is suggested that vaccination is one of the means
      to control colibacillosis, we tried to investigate the vaccine potential of a
      ?aroA derivative of an O78:K80 avian pathogenic Escherichia coli containing
      increased serum survival gene. 490 chicks were selected as follows: For
      assessment of virulence of ?aroA mutant, 30 chicks were divided into three groups
      and injected with 0.5ml of PBS or bacterial suspension containing either10(7)
      colony forming units (CFU) of mutant or parent strains via subcutaneous route.
      Macroscopic lesions and mortality rate were recorded in different groups during
      the week after challenge. For assessment of safety and immunogenicity of the
      ?aroA mutant, three groups of 20 chicks were vaccinated by aerosol administration
      of 250 ml of suspension containing 10(8) CFU of mutant strain at days 1 and 14,
      while the two other groups received PBS or wild type strain. Macroscopic lesions
      and mortality rate were recorded in different groups until day 21. To determine
      whether the vaccination is protective against challenges or not, the chickens
      were vaccinated at days 1 and 14 and challenged intramuscularly with either a
      homologous or heterologous strains at day 21. Macroscopic lesions and mortality
      rate were recorded in different groups during the week after challenge. The
      results revealed that the ?aroA mutant was slightly virulent, however it was safe
      and did not cause mortality, lesions or weight loss after vaccination. Antibody
      responses were similar in the control and mutant groups and vaccination did not
      induce a significant humoral immunity. The mutant could not protect chickens
      against both homologous and heterologous challenges. This could be due to several
      factors such as the high amount of maternal antibodies in the first two weeks of
      life, and the vaccination procedure. 

PMID- 24031841
TI  - Biofilm production by clinical staphylococci strains from canine otitis.
AB  - This study determined the species of 54 staphylococci isolates from canine otitis
      and their ability to produce biofilm through the Congo red agar method, confirmed
      by scanning electron microscopy. The most frequently identified species were S.
      intermedius and S. simulans. Results showed that 30% of the strains were biofilm
      producers. 

PMID- 24031842
TI  - Phenotypical characterization and adhesin identification in Escherichia coli
      strains isolated from dogs with urinary tract infections.
AB  - Pathogenic strains of Escherichia coli are the most common bacteria associated
      with urinary tract infections in both humans and companion animals. Standard
      biochemical tests may be useful in demonstrating detailed phenotypical
      characteristics of these strains. Thirteen strains of E. coli isolated from dogs
      with UTIs were submitted to biochemical tests, serotyping for O and H antigens
      and antimicrobial resistance testing. Furthermore, the presence of papC, sfa, and
      afa genes was evaluated by PCR, and genetic relationships were established using
      enterobacterial repetitive intergenic consensus PCR (ERIC-PCR). The antimicrobial
      that showed the highest resistance rate among the isolates was nalidixic acid
      (76.9%), followed by cephalotin (69.2%), sulfamethoxazole + trimethoprim (61.5%),
      tetracycline (61.5%), streptomycin (53.8%), ciprofloxacin (53.8%), ampicillin
      (46.2%), gentamicin (30.8%) and chloramphenicol (23.1%). No isolate was resistant
      either to meropenem or nitrofurantoin. Among the five clusters that were
      identified using ERIC-PCR, one cluster (A) had only one strain, which belonged to
      a serotype with zoonotic potential (O6:H31) and showed the genes papC+, sfa+, afa
      . Strains with the genes papC-, sfa+, afa- were found in two other clusters (C
      and D), whereas all strains in clusters B and E possessed papC-, sfa-, afa-
      genes. Sucrose and raffinose phenotypic tests showed some ability in
      discriminating clusters A, B and C from clusters D and E. 

PMID- 24031843
TI  - Characterization of pathogenic Aeromonas veronii bv. veronii associated with
      ulcerative syndrome from chinese longsnout catfish (Leiocassis longirostris
      Gunther).
AB  - 273 bacterial strains were isolated from 20 Chinese longsnout catfish samples.
      The biochemical characteristics of all strains conformed to the species
      description of Aeromonas veronii bv. veronii on the basis of Vitek GNI+ card.
      Furthermore, 16S rDNA, gyrB and rpoD sequences of the representative strain PY50
      were sequenced and showed high similarity with A. veronii bv. veronii in Genbank.
      Antibiotic-resistance of the representative strain PY50 was assessed by the Kirby
      Bauer disk diffusion method, and the results showed it was susceptible and
      moderately susceptible to 13 and 4 of the 21 antimicrobial agents tested.
      Extracellular products of strain PY50 contained gelatinase, lecithinase,
      elastase, most of lipase and lipopolysaccharide. Virulence of strain PY50 and
      extracellular products to Chinese longsnout catfish were also tested, and LD50
      were about 3.47*10(4) CFU per fish and 11.22 MUg per fish in intraperitoneal
      injection respectively. This is the first report that A. veronii bv. veronii was
      the pathogenic agent of ulcerative syndrome in Chinese longsnout catfish. 

PMID- 24031844
TI  - Use of FTA elute card impregnated with cervicovaginal sample directly into the
      amplification reaction increases the detection of human papillomavirus DNA.
AB  - This study aimed to evaluate the use of the FTA elute card(TM) impregnated with
      cervicovaginal sample directly in the PCR amplification for detection of HPV-DNA.
      The results were compared to a reference technique. This method was more
      efficient than the protocol indicated by the manufacturer, identifying 91.7%
      against 54.2% of the positive samples. 

PMID- 24031845
TI  - Epstein-Barr virus-associated gastric carcinoma in Brazil: comparison between in
      situ hybridization and polymerase chain reaction detection.
AB  - Epstein-Barr virus (EBV) has been associated with 10% of gastric carcinomas. The
      aim of this study was to determine the frequency of EBV in gastric carcinomas in
      Brazil assessed by in situ hybridization (ISH) and PCR, which would contribute to
      the characterization of the clinical and pathological aspects of EBV-associated
      gastric carcinomas. One hundred and ninety-two gastric carcinoma cases were
      collected at hospitals in two Brazilian states. Seventy-three out of 151 cases
      were PCR(+), while 11/160 cases were ISH(+). Nine out of eleven ISH(+) cases
      displayed a diffuse staining pattern and 2 out of 11 a focal pattern. Both
      techniques showed that the EBV(+) cases were characterized by their association
      with males, older patients, lower gastric region, intestinal type, advanced stage
      and poorly to moderately differentiated tumors. The concordance between the two
      techniques was 55.8% (Cohen's kappa index = 0.034). Four cases were ISH(+)/PCR(
      ), while 49 cases were PCR(+)/ISH(-). Only two cases showed stained lymphocytes
      by ISH and one of them was PCR(-). The observed discrepancy between the two
      techniques could not be explained just by the elevated accuracy of PCR.
      ISH(+)/PCR(-) carcinomas may be encountered if EBV is not present in the whole
      tumor tissue or if there are polymorphisms in the sequences of the viral genome
      amplified. On the other hand, the high frequency of PCR(+) results associated
      with the absence of ISH staining in lymphocytes and/or tumors cells suggests that
      the virus may be present in tumor cells or other cell types without expressing
      EBER1, the target of the ISH technique. 

PMID- 24031846
TI  - Cloning of a novel xylanase gene from a newly isolated Fusarium sp. Q7-31 and its
      expression in Escherichia coli.
AB  - A strain of Q7-31 was isolated from Qinghai-Tibet Plateau and was identified as
      Fusarium sp. based on its morphological characteristics and ITS rDNA gene
      sequence analysis. It has the highest capacity of degrading cell wall activity
      compared with other 11 strains. To do research on its xylanase activity of
      Fusarium sp. Q7-31 while the degrading the rice cell walls, the complete gene
      xyn8 that encodes endo-1, 4-beta-xylanase secreted by Fusarium sp. Q7-31 was
      cloned and sequenced. The coding region of the gene is separated by two introns
      of 56bp and 55bp. It encodes 230 amino acid residues of a protein with a
      calculated molecular weight of 25.7 kDa. The animo acids sequence of xyn8 gene
      has higher similarity with those of family 11 of glycosyl hydrolases reported
      from other microorganisms. The nature peptide encodeing cDNA was subcloned into
      pGEX5x-1 expression vector. The recombinant plasmid was expressed in Escherichia
      coli BL21-CodonPlus (DE3)-RIL, and xylanase activity was measured. The expression
      fusion protein was identified by SDS-PAGE and Western blotting, a new specific
      band of about 52kDa was identified when induced by IPTG. Enzyme activity assay
      verified the recombinants proteins as a xylanase. A maxium activity of 2.34U/ mg,
      the xylanase had optimal activity at pH 6.0 and temperature 40C. 

PMID- 24031847
TI  - Probiotic features of two oral Lactobacillus isolates.
AB  - In this study, we checked lactobacilli strains of human origin for their
      potential as probiotic. Samples were collected from oral mucosa of 16 healthy
      individuals, out of which twenty isolates were obtained and two of them were
      selected and identified as Lactobacillus plantarum (G1) and L. casei (G3). Both
      isolates exhibited antagonistic action towards pathogenic microorganisms such as
      Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella
      abony, and Clostridium sporogenes, but not on the growth of Candida albicans. The
      bacteriocin activity against Staphylococcus aureus ATCC 6358-P was shown only by
      L. plantarum G1. Moreover, the isolates G1 and G3 showed good viability in the
      acid gastric environment and in the gut environment containing bovine bile salts.
      The viability of G1 and G3 isolates in the gastrointestinal tract, and the
      adhesion to the intestinal mucosa were also confirmed in vivo. The biochemical
      tests of blood samples revealed lower levels of serum triglycerides and
      cholesterol, as well as reduced activity of alkaline phosphatase in all
      lactobacilli-treated Wistar rats, compared to control ones. No toxicity for NMRI
      Ham mice was observed. According to our experimental results, these findings
      imply that L. plantarum G1 and L. casei G3 could be characterized as potential
      probiotics. 

PMID- 24031848
TI  - Comparative analysis of the intracerebral mouse protection test and serological
      method for potency assays of pertussis component in DTP vaccine.
AB  - The aim of this study was to compare the PSPT standardized in-house as an
      alternative to MPT for potency assays of pertussis component. Statistical
      analyses have showed similar pertussis potency values when PSPT was compared to
      MPT. Significant correlation between the potency results obtained by in vivo and
      in vitro assays was also been observed. Results by PSPT have demonstrated
      reproducibility and accuracy for potency pertussis control and this approach has
      been considered promising for use at least during the steps of production. 

PMID- 24031849
TI  - Evaluation of the composition of culture medium for yeast biomass production
      using raw glycerol from biodiesel synthesis.
AB  - The work herewith investigated the production of yeast biomass as a source of
      protein, using Yarrowia lipolytica NRRL YB-423 and raw glycerol from biodiesel
      synthesis as the main carbon source. A significant influence of glycerol
      concentration, initial pH and yeast extract concentration on biomass and protein
      content was observed according to the 2v (5-1) fractional design. These factors
      were further evaluated using a central composite design and response surface
      methodology, and an empirical model for protein content was established and
      validated. The biomass of Yarrowia lipolytica NRRL YB-423 reached 19.5 +/- 1.0
      g/L in shaken flasks cultivation, with a protein content of 20.1 +/- 0.6% (w/w). 

PMID- 24031850
TI  - Isolation and characterization of an Ashbya gossypii mutant for improved
      riboflavin production.
AB  - The use of the filamentous fungus, Ashbya gossypii, to improve riboflavin
      production at an industrial scale is described in this paper. A riboflavin
      overproducing strain was isolated by ultraviolet irradiation. Ten minutes after
      spore suspensions of A. gossypii were irradiated by ultraviolet light, a survival
      rate of 5.5% spores was observed, with 10% of the surviving spores giving rise to
      riboflavin-overproducing mutants. At this time point, a stable mutant of the wild
      strain was isolated. Riboflavin production of the mutant was two fold higher than
      that of the wild strain in flask culture. When the mutant was growing on the
      optimized medium, maximum riboflavin production could reach 6.38 g/l. It has even
      greater promise to increase its riboflavin production through dynamic analysis of
      its growth phase parameters, and riboflavin production could reach 8.12 g/l with
      pH was adjusted to the range of 6.0-7.0 using KH2PO4 in the later growth phase.
      This mutant has the potential to be used for industrial scale riboflavin
      production. 

PMID- 24031851
TI  - Characterizations of a new Cordyceps cicadae isolate and production of adenosine
      and cordycepin.
AB  - Cordyceps is a fastidious pathogenic fungus infecting insects, and recent years
      have witnessed rapid progress in its medical properties. In this study, a wild
      isolate, C. cicadae MP12, was characterized through in vitro cultivation and its
      nuclear small-subunit (SSU) ribosomal DNA (rDNA) data. In vitro culture of C.
      cicadae MP12 was established by growing its fruiting bodies in a solid matrix. C.
      cicadae MP12 was inoculated into Cryptotympana atrata cicada pupae for in vivo
      culture, where the fungi developed its fruiting body as well. The contents of
      adenosine and cordycepin in dried fruiting bodies after culture were 1421.45MUg/g
      and 1398.12 MUg/g, respectively. Therefore, the established cultures from this
      study could be used for the production of various medically important metabolic
      substances. 

PMID- 24031852
TI  - Hydrolysis of various thai agricultural biomasses using the crude enzyme from
      Aspergillus aculeatus iizuka FR60 isolated from soil.
AB  - In this study, forty-two fungi from soil were isolated and tested for their
      carboxymethyl cellulase (CMCase) and xylanase activities. From all isolates, the
      fungal isolate FR60, which was identified as Aspergillus aculeatus Iizuka, showed
      high activities in both CMCase and xylanase with 517 mU/mg protein and 550 mU/mg
      protein, respectively. The crude enzyme from A. aculeatus Iizuka FR60 could
      hydrolyze several agricultural residues such as corncob, and sweet sorghum leaf
      and stalk at comparable rates with respect to the tested commercial enzymes and
      with a maximum rate in rice hull hydrolysis (29 MUg sugar g(-1) dry weight
      substrate mg(-1) enzyme hr(-1)). The highest amount of glucose was obtained from
      corncob by using the crude enzyme from A. aculeatus Iizuka FR60 (10.1 g/100 g dry
      substrate). From overall enzymatic treatment results, the lowest sugar yield was
      from rice hulls treatment (1.6 g/100 g dry weight) and the highest amount of
      reducing sugar was obtained from rice straw treatment (15.3 g/100 g dry weight).
      Among tested agricultural wastes, rice hull could not be effectively hydrolyzed
      by enzymes, whereas sugarcane leaf and stalk, and peanut shell could be
      effectively hydrolyzed (30-31% total sugar comparing with total sugar yield from
      acid treatment). 

PMID- 24031853
TI  - A biodegradation study of forest biomass by Aspergillus niger F7: correlation
      between enzymatic activity, hydrolytic percentage and biodegradation index.
AB  - Aspergillus niger F7 isolated from soil was found to be the potent producer of
      cellulase and xylanase. The residue of forest species Toona ciliata, Celtris
      australis, Cedrus deodara and Pinus roxburghii was selected as substrate for
      biodegradation study due to its easy availability and wide use in industry. It
      was subjected to alkali (sodium hydroxide) treatment for enhancing its
      degradation. Biodegradation of forest waste by hydrolytic enzymes (cellulase and
      xylanase) secreted by A. niger under solid state fermentation (SSF) was explored.
      SSF of pretreated forest biomass was found to be superior over untreated forest
      biomass. Highest extracellular enzyme activity of 2201+/-23.91 U/g by A. niger
      was shown in pretreated C. australis wood resulting in 6.72+/-0.20 percent
      hydrolysis and 6.99+/-0.23 biodegradation index (BI). The lowest BI of 1.40+/
      0.08 was observed in untreated saw dust of C. deodara having the least enzyme
      activity of 238+/-1.36 U/g of dry matter. Biodegradation of forest biomass under
      SSF was increased many folds when moistening agent i.e. tap water had been
      replaced with modified basal salt media (BSM). In BSM mediated degradation of
      forest waste with A. niger, extracellular enzyme activity was increased up to
      4089+/-67.11 U/g of dry matter in turn resulting in higher BI of 15.4+/-0.41 and
      percent hydrolysis of 19.38+/-0.81 in pretreated C. australis wood. A. niger
      exhibited higher enzyme activity on pretreated biomass when moistened with
      modified BSM in this study. Statistically a positive correlation has been drawn
      between these three factors i.e. enzyme activity, BI and percent hydrolysis of
      forest biomass thus proving their direct relationship with each other. 

PMID- 24031854
TI  - Penicillin production by wild isolates of Penicillium chrysogenum in Pakistan.
AB  - The present study was aimed at exploring the native wild isolates of Penicillium
      chrysogenum series in terms of their penicillin production potential. Apart from
      the standard medium, the efforts were made to utilize suitable agro-industrial
      wastes for the maximum yield of penicillin. Two series of P. chrysogenum were
      isolated from local sources and named as P. chrysogenum series UAF R1 and P.
      chrysogenum series UAF R2. The native series were found to possess better
      penicillin production potential than the already reported series of P.
      chrysogenum. However, P. chrysogenum series UAF R1 was found to be the best
      candidate for high yield of penicillin starting at 100 hour as compared to P.
      chrysogenum series UAF R2 which produced the highest yield of penicillin at 150
      hours for a shorter period of time. Addition of Corn Steep Liquor (CSL) to the
      fermentation medium resulted in the production of 1.20g/L penicillin by P.
      chrysogenum series UAF R1 and P. chrysogenum series UAF R2. The fermentation
      medium in which Sugar Cane Bagasse (SCB) was replaced with CSL resulted in the
      highest yield of penicillin (1.92g/L) by both native series of P. chrysogenum.
      The penicillin production was increased by 62.5% in medium with SCB as compared
      to that with CSL. The penicillin yield of medium containing lactose and phenyl
      acetate was higher than that of control medium. Overall results revealed that P.
      chrysogenum series UAF R1 and P. chrysogenum series UAF R2 may be recommended for
      better yield of natural penicillin and this efficiency may be further enhanced by
      utilizing SCB as substrate in the growth medium. 

PMID- 24031855
TI  - Development and characterization of hybrids from native wine yeasts.
AB  - For commercial purposes, the winemaking industry is constantly searching for new
      yeast strains. Historically, this has been achieved by collecting wild strains
      and selecting the best for industrial use through an enological evaluation.
      Furthermore, the increasing consumer demands have forced the industry to
      incorporate new strategies such as genetic engineering to obtain improved
      strains. In response to the lack of public acceptance of this methodology,
      alternative strategies based on breeding have gained acceptance in recent years.
      Through the use of conjugation of individual spores without the support of
      genetic engineering methods we generated intraspecific hybrids from wild strains
      with outstanding enological characteristics and interdelta fingerprinting was
      used to confirm the hybrid condition. A detailed enological characterization of
      the hybrids in synthetic and natural must indicates that physiological parameters
      such as sporulation, residual sugar, ethanol yield and total nitrogen uptake are
      within the levels determined for the parental strains, however, other parameters
      such as growth rate, lag phase and ethanol production show statistical
      differences with some parental or commercial strains. These findings allow us to
      propose these hybrids as new wine-making strains. 

PMID- 24031856
TI  - Optimization of exopolysaccharides production from a novel strain of Ganoderma
      lucidum CAU5501 in submerged culture.
AB  - This study aimed at optimizing the medium of a new Ganoderma lucidum strain
      CAU5501 to enhance the yield of exopolysaccharides (EPS) and mycelial growth.
      Firstly, the suitable level of glucose, magnesium, phosphate and C/N ratio was
      determined by single factor experiment. Subsequently, the optimum concentrations
      of these medium components were investigated using the orthogonal matrix method.
      The results indicated that the higher levels of EPS were correlated with the
      level of cell growth when glucose concentration was studied (data no show). The
      optimum medium for EPS yield was found to be 70 g/l glucose, 5 C/N ratio, 2.5 g/l
      KH2PO4, 0.75 g/l MgSO4.7H2O, and for mycelial growth was 50 g/l glucose, 5 C/N
      ratio, 1.5 g/l KH2PO4, 0.5 g/l MgSO4.7H2O. When cultivated in the obtained
      optimal media in 3 L shake flask, compared to the basal medium, the EPS yield
      increased markedly from 1.003 to 1.723 g/l, and the mycelium formation was also
      markedly improved from 2.028 to 7.235 g/l. Results obtained in this study are
      beneficial to further study for enhancing the production of Ganoderma lucidum
      polysaccharides in large scale commercialized production. 

PMID- 24031857
TI  - The hydrolysis of agro-industrial residues by holocellulose-degrading enzymes.
AB  - Holocellulose structures from agro-industrial residues rely on main and side
      chain attacking enzymes with different specificities for complete hydrolysis.
      Combinations of crude enzymatic extracts from different fungal species, including
      Aspergillus terreus, Aspergillus oryzae, Aspergillus niger and Trichoderma
      longibrachiatum, were applied to sugar cane bagasse, banana stem and dirty cotton
      residue to investigate the hydrolysis of holocellulose structures. A. terreus and
      A. oryzae were the best producers of FPase and xylanase activities. A combination
      of A. terreus and A. oryzae extracts in a 50% proportion provided optimal
      hydrolysis of dirty cotton residue and banana stem. For the hydrolysis of sugar
      cane bagasse, the best results were obtained with samples only containing A.
      terreus crude extract. 

PMID- 24031858
TI  - Bioconversion of glycerol for bioethanol production using isolated Escherichia
      coli ss1.
AB  - Bioconverting glycerol into various valuable products is one of glycerol's
      promising applications due to its high availability at low cost and the existence
      of many glycerol-utilizing microorganisms. Bioethanol and biohydrogen, which are
      types of renewable fuels, are two examples of bioconverted products. The
      objectives of this study were to evaluate ethanol production from different media
      by local microorganism isolates and compare the ethanol fermentation profile of
      the selected strains to use of glucose or glycerol as sole carbon sources. The
      ethanol fermentations by six isolates were evaluated after a preliminary
      screening process. Strain named SS1 produced the highest ethanol yield of 1.0
      mol: 1.0 mol glycerol and was identified as Escherichia coli SS1 Also, this
      isolated strain showed a higher affinity to glycerol than glucose for bioethanol
      production. 

PMID- 24031859
TI  - Comparison of different protocols for the extraction of microbial DNA from reef
      corals.
AB  - This study aimed to test different protocols for the extraction of microbial DNA
      from the coral Mussismilia harttii. Four different commercial kits were tested,
      three of them based on methods for DNA extraction from soil (FastDNA SPIN Kit for
      soil, MP Bio, PowerSoil DNA Isolation Kit, MoBio, and ZR Soil Microbe DNA Kit,
      Zymo Research) and one kit for DNA extraction from plants (UltraClean Plant DNA
      Isolation Kit, MoBio). Five polyps of the same colony of M. harttii were
      macerated and aliquots were submitted to DNA extraction by the different kits.
      After extraction, the DNA was quantified and PCR-DGGE was used to study the
      molecular fingerprint of Bacteria and Eukarya. Among the four kits tested, the ZR
      Soil Microbe DNA Kit was the most efficient with respect to the amount of DNA
      extracted, yielding about three times more DNA than the other kits. Also, we
      observed a higher number and intensities of DGGE bands for both Bacteria and
      Eukarya with the same kit. Considering these results, we suggested that the ZR
      Soil Microbe DNA Kit is the best adapted for the study of the microbial
      communities of corals. 

PMID- 24031860
TI  - Occurrence and characteristics of virulence genes of Escherichia coli strains
      isolated from healthy dairy cows in Inner Mongolia, China.
AB  - Virulence genes of Escherichia coli (E. coli) isolates from healthy dairy cows
      were identified and characterized by a multiplex PCR assay and serogrouping test.
      The results showed that among the target genes, eaeA was most frequently
      detected, accounting for 22.11% (67/303) in all strains from 101 cows. For
      categorization of E. coli, aEPEC was the category with widest distribution
      detected in 55 (18.15%) strains from 22 cattle. All of 84 PCR-positive strains
      belonged to 14 O serogroups, and O149 (25.00%) was most common identified,
      followed by O2 (17.86%), O8 (11.90%) and O103 (9.52%) with relatively high
      prevalence. 

PMID- 24031861
TI  - Transmission OF Campylobacter coli in chicken embryos.
AB  - Campylobacter coli is an important species involved in human cases of enteritis,
      and chickens are carriers of the pathogen mainly in developing country. The
      current study aimed to evaluate the transmission of C. coli and its pathogenic
      effects in chicken embryos. Breeder hens were inoculated intra-esophageally with
      C. coli isolated from chickens, and their eggs and embryos were analyzed for the
      presence of bacteria using real-time PCR and plate culture. The viability of
      embryos was verified. In parallel, SPF eggs were inoculated with C. coli in the
      air sac; after incubation, the embryos were submitted to the same analysis as the
      embryos from breeder hens. In embryos and fertile eggs from breeder hens, the
      bacterium was only identified by molecular methods; in the SPF eggs, however, the
      bacterium was detected by both techniques. The results showed no relationship
      between embryo mortality and positivity for C. coli in the embryos from breeder
      hens. However, the presence of bacteria is a cause of precocious mortality for
      SPF embryos. This study revealed that although the vertical transmission is a
      possible event, the bacteria can not grow in embryonic field samples. 

PMID- 24031862
TI  - Growth inhibition of Staphylococcus aureus and escherichia coli strains by
      neutralizing IgY antibodies from ostrich egg yolk.
AB  - Ostrich raising around the world have some key factors and farming profit depend
      largely on information and ability of farmers to rear these animals. Non
      fertilized eggs from ostriches are discharged in the reproduction season.
      Staphylococcus aureus and Escherichia coli are microorganisms involved in animal
      and human diseases. In order to optimize the use of sub products of ostrich
      raising, non fertilized eggs of four selected birds were utilized for development
      of polyclonal IgY antibodies. The birds were immunized (200ug/animal) with
      purified recombinant staphylococcal enterotoxin C (recSEC) and synthetic recRAP,
      both derived from S. aureus, and recBFPA and recEspB involved in E. coli
      pathogenicity, diluted in FCA injected in the braquial muscle. Two subsequent
      immunization steps with 21 days intervals were repeated in 0,85% saline in FIA.
      Blood and eggs samples were collected before and after immunization steps. Egg
      yolk immunoglobulins were purified by precipitation with 19% sodium sulfate and
      20% ammonium sulphate methodologies. Purified IgY 50MUL aliquots were incubated
      in 850MUL BHI broth containing 50MUL inoculums of five strains of S. aureus and
      five strains of E.coli during four hours at 37 degrees C. Growth inhibition was
      evaluated followed by photometry reading (DO550nm). Egg yolk IgY preparation from
      hiperimmunized birds contained antibodies that inhibited significantly (p<0,05)
      growth of strains tested. Potential use of ostrich IgY polyclonal antibodies as a
      diagnostic and therapeutic tool is proposed for diseased animals. 

PMID- 24031863
TI  - Synergistic haemolytic activity and its correlation to phospholipase D
      productivity by Corynebacteruim pseudotuberculosis Egyptian isolates from sheep
      and buffaloes.
AB  - Fourteen isolates of Corynebacteruim pseudotuberculosis of them 7 were isolated
      from sheep with Caseous Lymphadenitis "biotype 1" and 7 isolated from buffaloes
      with Oedematous Skin Disease "biotype 2". All isolates were identified by
      standard microbiological techniques and by polymerase chain reaction targeting,
      16S rRNA and phospholipase D genes. Synergistic haemolytic titers of all isolates
      were assayed by plate technique. The presences of phospholipase D gene in
      supernatants of all isolates were performed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis immunoblot technique by using hyperimmune
      serum raised in rabbit immunized with recombinant phospholipase D gene antigen.
      The concentration of phospholipase D gene was assayed by scanning the bound
      phospholipase D gene with specific antibodies that appeared at 31.5 kDa. Results
      presented that there is no correlation between titer of Synergistic haemolytic
      activity and the actual phospholipase D genes concentration in culture
      supernatants. Also results presented that Synergistic haemolytic activity and
      phospholipase D genes produced by biotype 2 (buffalo isolates) was generally
      higher than those by biotype 1(sheep isolates). 

PMID- 24031864
TI  - Isolation and identification of feline calicivirus and feline herpesvirus in
      Southern Brazil.
AB  - Feline calicivirus (FCV) and feline herpesvirus type 1 (FHV-1) are the two
      primary causes of upper respiratory tract disease in cats. The aim of this study
      was to demonstrate the distribution of FCV and FHV-1 among the feline population
      of several counties in Rio Grande do Sul State, Brazil. To this end, conjunctival
      and nasal swabs were collected from 302 cats from different locations, including
      households, breeding catteries, veterinary clinics, animal hospitals and
      experimental research facilities. The samples were collected between July 2006 to
      June 2009. The virus isolation was performed in CRFK cells and, subsequently, the
      identification was confirmed by PCR. FCV, FHV-1, or both were isolated from 55
      cats from 28 different locations. FCV alone was isolated from 52.7% (29/55) of
      the animals that tested positively, FHV-1 alone was isolated from 38.2% (21/55)
      of the animals that tested positively, and co-infection were detected in 9.1%
      (5/55) of the animals that tested positively. Virus detection was more prevalent
      in cats that were less than 1 year old, among animals that shared a living space
      with other cats, and females. FCV and FHV-1 were isolated from vaccinated cats.
      In addition, both viruses were isolated from cats that showed no signs of
      disease. The results suggest that a carrier state is common for both viruses in
      the evaluated population. A search for other causes of respiratory disease in
      that population is necessary; and further studies relating to the molecular
      characterization of viruses and vaccine efficacy are also necessary. 

PMID- 24031865
TI  - Molecular detection of hemoplasma infection among cats from Sao Luis island,
      Maranhao, Brazil.
AB  - Hemoplasmas are bacteria that infect erythrocytes, attaching to the red blood
      cell. There is a need for more reports of hemoplasma infection prevalence and
      molecular characterization among cats in Brazil since there are only few
      published reports. The present work aimed to detect and molecularly characterize
      the presence of hemotrophic mycoplasmas in domestic cats with outdoor access from
      Sao Luis, Maranhao, Brazil. Twenty cats (10%) were positive for Candidatus M.
      haemominutum, five (2.5%) for M. haemofelis, and four (2.%) for M. turicensis
      based on 16S rRNA gene PCRs. Five cats (2.5%) were co-positive for Candidatus M.
      haemominutum and M. haemofelis. PCR diagnosis was confirmed by sequencing; and
      phylogenetic analysis was based on 16S rRNA and rnpb genes. 

PMID- 24031866
TI  - Streptococcus iniae outbreaks in Brazilian Nile tilapia (Oreochromis niloticus
      L:) farms.
AB  - This is the first report of outbreaks of Streptococcus iniae in Nile tilapia
      farms in South America. Seven isolates were identified by biochemical,
      serological and molecular tests. Their 16S rRNA gene sequences showed 100%
      similarity with S. iniae ATCC 29178 and two distinct PFGE patterns were observed
      for Brazilian isolates. 

PMID- 24031867
TI  - Diagnosis of paratuberculosis in cattle: microbiological culture, serology and
      PCR.
AB  - The aim of this study was to confirm clinical diagnosis of paratuberculosis in
      two cows showing suggestive clinical signs of the disease. Based on clinical
      signs, in culture and in IS900 PCR results from the individual milk samples it
      was possible to diagnose paratuberculosis in the cows studied. 

PMID- 24031868
TI  - Analysis of isotype-specific antibody responses to bovine herpesviruses 1.1 and
      1.2a allows to estimate the stage of infection.
AB  - Specific IgM, IgA, IgG1, IgG2, as well as neutralizing antibody responses were
      evaluated in sera of calves experimentally infected with two isolates of bovine
      herpesvirus type 1 (BoHV1) of distinct subtypes (subtype 1, BoHV1.1; subtype 2a,
      BoHV-1.2a). No significant differences were observed in the antibody responses
      induced by each BoHV-1 subtype. The antibody responses following primary acute
      infection were characterized by an increase in specific IgM and IgA levels
      between days 2 and 14 post inoculation (pi). IgG1 was detected from days 11 to 30
      pi. IgG2 was detected on the sample taken on day 30 pi. Reactivation of infection
      following dexamethasone administration induced a significant rise in IgA levels,
      whereas IgG1 and IgG2 levels, which were at high levels from the beginning of the
      reactivation process, showed a slight alteration after corticosteroid treatment.
      These results suggest that it is possible to estimate the dynamics of BoHV-1
      infections with basis on the analysis of class- and subclass-specific antibody
      responses. Such information may be particularly useful for the study of the
      kinetics of the infection in a herd and to aid in the adoption of appropriate
      control measures.. 

PMID- 24031869
TI  - Excretion of Brucella abortus vaccine B19 strain during a reproductive cycle in
      dairy cows.
AB  - This paper aimed to determine the excretion period of B19 vaccine strain during a
      complete reproductive cycle (from estrus synchronization, artificial
      insemination, pregnancy and until 30 days after parturition) of dairy cows from 3
      to 9 years old that were previously vaccinated from 3 to 8 months. Three groups
      were monitored with monthly milk and urine collection during 12 months: G1 with
      seven cows from 3 to 4 years old; G2 with three cows from 5 to 6 years old; and
      G3 with four cows from 7 to 9 years old. Urine and milk samples were submitted to
      bacteriological culture and urine and PCR reactions for detection of Brucella
      spp. and PCR-multiplex for B19 strain identification. Ring test (RT) was also
      performed in the milk samples, and serum samples were tested by buffered
      acidified plate antigen test (BAPA). All animals were serologically negative at
      BAPA and Brucella spp. was not isolated from both urine and milk samples. RT
      revealed 13/210 (6.2%) positive milk samples. PCR reactions detected DNA of
      Brucella spp. in 86/420 (20.5%) samples. In urine it was found a significantly
      higher frequency (35.2%; 74/210) than in milk (5.7%; 12/210), more frequently
      from the estrus to 150 days of pregnancy and after parturition (6.7%; 10/150),
      and from 150 days of pregnancy to parturition (3.4%; 2/60), and they were all
      identified as B19 strain. In three groups, intermittent excretion of B19 strain
      was detected mainly in urine samples, which confirmed its multiplication and
      persistence in cows for until 9 years. 

PMID- 24031870
TI  - Diagnosis of canine leptospirosis using an immunomagnetic separation-PCR method.
AB  - Diagnosis of leptospirosis by PCR is hampered due to the presence of substances
      on biological fluids. Here, we report an immunomagnetic separation step prior to
      PCR which improved the detection of Leptospira spp. in blood and urine samples
      from dogs. It resulted in a significant improvement on sensitivity for diagnosis
      of canine leptospirosis. 

PMID- 24031871
TI  - Characterization of pyrene utilizing Bacillus spp. from crude oil contaminated
      soil.
AB  - Pyrene, a high molecular weight polycyclic aromatic hydrocarbon (PAH), is a
      priority pollutant present in soil contaminated with crude oil, coal-tar and
      complex PAHs. Bacterial consortium CON-3 developed from crude oil contaminated
      soil of Patiala, Punjab (India) cometabolized 50 MUg ml(-1) pyrene in the
      presence of glucose (0.5 %; w/v) at 30  degrees C, as determined by reverse-phase
      high performance liquid chromatography (HPLC). Bacillus sp. PK-12, Bacillus sp.
      PK-13 and Bacillus sp. PK-14 from CON-3, identified by 16S rRNA gene sequence
      analysis, were able to cometabolize 64 %, 55 % and 53 % of pyrene in 35 days,
      respectively. With the increase in glucose concentration to 1.0 % (w/v) in growth
      medium isolates PK-12, PK-13 and PK-14 showed 19 - 46 % uptake of 50 MUg ml(-1)
      pyrene in 4 days, respectively. Uptake of pyrene was correlated with growth and
      biosurfactant activity, which is suggestive of the potential role of members of
      Bacillus genera in pyrene mobilization and its uptake. 

PMID- 24031872
TI  - Bacillus thuringiensis monogenic strains: screening and interactions with
      insecticides used against rice pests.
AB  - The screening of Bacillus thuringiensis (Bt) Cry proteins with high potential to
      control insect pests has been the goal of numerous research groups. In this
      study, we evaluated six monogenic Bt strains (Bt dendrolimus HD-37, Bt kurstaki
      HD-1, Bt kurstaki HD-73, Bt thuringiensis 4412, Bt kurstaki NRD-12 and Bt
      entomocidus 60.5, which codify the cry1Aa, cry1Ab, cry1Ac, cry1Ba, cry1C, cry2A
      genes respectively) as potential insecticides for the most important insect pests
      of irrigated rice: Spodoptera frugiperda, Diatraea saccharalis, Oryzophagus
      oryzae, Oebalus poecilus and Tibraca limbativentris. We also analyzed their
      compatibility with chemical insecticides (thiamethoxam, labdacyhalothrin,
      malathion and fipronil), which are extensively used in rice crops. The bioassay
      results showed that Bt thuringiensis 4412 and Bt entomocidus 60.5 were the most
      toxic for the lepidopterans, with a 93% and 82% mortality rate for S. frugiperda
      and D. saccharalis, respectively. For O. oryzae, the Bt kurstaki NRD-12 (64%) and
      Bt dendrolimus HD-37 (62%) strains were the most toxic. The Bt dendrolimus HD-37
      strain also caused high mortality (82%) to O. poecilus, however the strains
      assessed to T. limbativentris caused a maximum rate of 5%. The assays for the Bt
      strains interaction with insecticides revealed the compatibility of the six
      strains with the four insecticides tested. The results from this study showed the
      high potential of cry1Aa and cry1Ba genes for genetic engineering of rice plants
      or the strains to biopesticide formulations. 

PMID- 24031873
TI  - Biodiversity of the oleaginous microorganisms in Tibetan Plateau.
AB  - Microbial lipids, which are also known as single cell oils (SCO), are produced by
      oleaginous microorganisms including oleaginous bacteria, yeast, fungus and algae
      through converting carbohydrates into lipids under certain conditions. Due to its
      unique environment having extremely low temperature and anoxia, the Tibetan
      Plateau is amongst the regions with numerous rare ecotypes such as arid desert,
      salt marsh, alpine permafrost, hot spring, and lawn. By using a rapid, convenient
      screening method, we identified 31 strains of oleaginous microorganisms from
      different habitats in the Tibetan Plateau, which include wetlands, lawn, hot
      spring, alpine permafrost, and saline-alkali soil. Molecular identity analysis
      showed that they belong to 15 different species, 7 of which are reported for the
      first time as lipid-producing microorganisms, that is, Cladosporium sp.,
      Gibberella fujikuro, Ochrobactrum sp., Plectosphaerella sp., Tilletiopsis
      albescens, Backusella ctenidia, and Davidiella tassiana. The distribution of the
      oleaginous microorganisms varies with habitats. 11 strains were found in hot
      spring (35.5%), 10 in farmland (32.3%), 6 in lawn (19.4%), 2 in sand (6.4%), 1 in
      wetland (3.2%), and 1 in permafrost (3.2%). Carbon utilization analysis indicated
      that most of these filamentous fungi can use xylose and carboxymethyl cellulose
      (CMC) as carbon source, where Backusella ctenidia, Fusarium sp. and Gibberella
      fujikuroi have the strongest capability. 

PMID- 24031874
TI  - Vibrio cholerae O1 from superficial water of the Tucunduba Stream, Brazilian
      Amazon.
AB  - Isolation and genetic characterization of an environmental Vibrio cholerae O1
      from the Amazon is reported. This strain lacks two major virulence factors - CTX
      and TCP - but carries other genes related to virulence. Genetic similarity with
      epidemic strains is evaluated and the importance of V. cholerae surveillance in
      the Amazon is emphasized. 

PMID- 24031875
TI  - Evaluation and biochemical characterization of a distinctive pyoverdin from a
      pseudomonas isolated from chickpea rhizosphere.
AB  - Microbial siderophores confiscate the available ferric ions around the roots and
      trigger a reaction resulting in plant growth promotion. In our study, a high
      level of siderophore production was observed from a newly isolated Pseudomonas
      sp. from the rhizosphere of Chickpea plants. Under an iron depleted condition in
      Standard Succinic acid medium a 1000 MUgmL(-1) of siderophore production was
      achieved. Increasing the concentration of iron showed an inverse relationship
      between growth and siderophore production. Fourier Transform Infrared
      Spectroscopy (FTIR) analysis of the purified crystals, its UV spectral analysis
      and High Pressure Liquid Chromatography (HPLC) revealed the identity of the
      siderophore as similar to that of pyoverdin with distinctive characters. Electron
      spray ionization mass spectroscopy (ESIMS) shows presence of abundance of A1 ions
      (419 m/z) and branching of amino acids from B1-B5. This pyoverdin contains a
      cyclic tetra peptide but Serine and Arginine are missing. Based on our analysis
      and deviations from the reported structure of pyoverdin it is suggested that this
      pseudomonas produces distinctly characterized pyoverdin siderophore. 

PMID- 24031876
TI  - A comparison of silver staining protocols for detecting DNA in polyester-backed
      polyacrylamide gel.
AB  - Eight silver-staining protocols were applied to detect DNA in polyester-backed
      gels to select the optimal. Results showed important differences in staining
      quality and that four methods were well-suited for TGGE gels due to high
      sensitivity and low background, including the Bassam et al. methods, the
      manufacturer method and our improved method. 

PMID- 24031877
TI  - Interspecific variation of the bacterial community structure in the phyllosphere
      of the three major plant components of mangrove forests.
AB  - Mangrove forests encompass a group of trees species that inhabit the intertidal
      zones, where soil is characterized by the high salinity and low availability of
      oxygen. The phyllosphere of these trees represent the habitat provided on the
      aboveground parts of plants, supporting in a global scale, a large and complex
      microbial community. The structure of phyllosphere communities reflects
      immigration, survival and growth of microbial colonizers, which is influenced by
      numerous environmental factors in addition to leaf physical and chemical
      properties. Here, a combination of culture-base methods with PCR-DGGE was applied
      to test whether local or plant specific factors shape the bacterial community of
      the phyllosphere from three plant species (Avicenia shaueriana, Laguncularia
      racemosa and Rhizophora mangle), found in two mangroves. The number of bacteria
      in the phyllosphere of these plants varied between 3.62 x 10(4) in A. schaeriana
      and 6.26 x 10(3) in R. mangle. The results obtained by PCR-DGGE and isolation
      approaches were congruent and demonstrated that each plant species harbor
      specific bacterial communities in their leaves surfaces. Moreover, the ordination
      of environmental factors (mangrove and plant species), by redundancy analysis
      (RDA), also indicated that the selection exerted by plant species is higher than
      mangrove location on bacterial communities at phyllosphere. 

PMID- 24031878
TI  - Prokaryotic communities of acidic peatlands from the southern Brazilian Atlantic
      Forest.
AB  - The acidic peatlands of southern Brazil are ecosystems essential for the
      maintenance of the Atlantic Forest, one of the 25 hot-spots of biodiversity in
      the world. In this work, we investigated the composition of prokaryotic
      communities in four histosols of three acidic peatland regions by constructing
      small-subunit (SSU) rRNA gene libraries and sequencing. SSU rRNA gene sequence
      analysis showed the prevalence of Acidobacteria (38.8%) and Proteobacteria
      (27.4%) of the Bacteria domain and Miscellaneous (58%) and Terrestrial (24%)
      groups of Crenarchaeota of the Archaea domain. As observed in other ecosystems,
      archaeal communities showed lower richness than bacterial communities. We also
      found a limited number of Euryarchaeota and of known methanotrophic bacteria in
      the clone libraries. 

PMID- 24031879
TI  - Comparison of thermotolerant coliforms and Escherichia coli densities in
      freshwater bodies.
AB  - Fecal bacterial indicator analyses have been widely used for monitoring the water
      quality. This study was designed to determine the ratio between the density of
      Escherichia coli and other Thermotolerant Coliforms (TtC) bacteria from
      freshwater samples collected for a two-year period of monitoring. TtC were
      enumerated by membrane filtration on mFC agar. E. coli enumeration was done by
      two methods: TtC colonies identified in mFC were inoculated in EC-MUG or water
      samples were filtered and inoculated in modified mTEC agar media, and both
      methods were compared for quantitative recovery of E. coli. The results pointed
      out a mean percentage of E. coli among other thermotolerant coliforms (E.
      coli/TtC ratio) of 84.3% in mFC media. Taking these results into account, a
      mandatory standard of 1000 thermotolerant coliforms would correspond to 800 E.
      coli and the adoption of these E. coli based standards will represent a major
      improvement for the monitoring of freshwater quality. 

PMID- 24031880
TI  - Genetic diversity of Rhizobia isolates from Amazon soils using cowpea (Vigna
      unguiculata) as trap plant.
AB  - The aim of this work was to characterize rhizobia isolated from the root nodules
      of cowpea (Vigna unguiculata) plants cultivated in Amazon soils samples by means
      of ARDRA (Amplified rDNA Restriction Analysis) and sequencing analysis, to know
      their phylogenetic relationships. The 16S rRNA gene of rhizobia was amplified by
      PCR (polymerase chain reaction) using universal primers Y1 and Y3. The
      amplification products were analyzed by the restriction enzymes HinfI, MspI and
      DdeI and also sequenced with Y1, Y3 and six intermediate primers. The clustering
      analysis based on ARDRA profiles separated the Amazon isolates in three
      subgroups, which formed a group apart from the reference isolates of
      Bradyrhizobium japonicum and Bradyrhizobium elkanii. The clustering analysis of
      16S rRNA gene sequences showed that the fast-growing isolates had similarity with
      Enterobacter, Rhizobium, Klebsiella and Bradyrhizobium and all the slow-growing
      clustered close to Bradyrhizobium. 

PMID- 24031881
TI  - Association of TLR4 polymorphisms with subclinical mastitis in Brazilian
      holsteins.
AB  - The identification of dairy cows with greater or lower potential to develop
      mastits has been pursued for many years among different segments of the milk
      industry, including governmental organizations. Genomic studies have suggested
      that Single Nucleotide Polymorphisms (SNPs) within the pattern recognition
      receptors (PRR) could lead to different responses to pathogens, and consequently
      result in mastitis resistance or susceptibility. To investigate whether toll like
      receptor 4 (TLR4) gene is associated with subclinical mastitis in Holstein cows
      from a property in the state of Goias, Brazil, TaqMan allelic discrimination and
      somatic cell count were performed. One hundred and fifty milk samples were
      analyzed for SCC and centesimal composition. Twenty percent of those samples with
      SCC above 200,000 (n=13) were screened for real-time PCR identification of
      microorganisms and blood samples were genotyped for TLR4 SNPs. There was a higher
      prevalence of Gram-positive bacteria in the analyzed samples (88.9%) and animals
      that had the combined genotypes AACCCC, GGTCGG and GACCGC presented the lowest
      somatic cell scores, and consequently those genotypes have the potential to be
      applied as molecular markers for assisted animal selection to improve milk
      quality. 

PMID- 24031882
TI  - Multilocus sequence analysis (MLSA) of Bradyrhizobium strains: revealing high
      diversity of tropical diazotrophic symbiotic bacteria.
AB  - Symbiotic association of several genera of bacteria collectively called as
      rhizobia and plants belonging to the family Leguminosae (=Fabaceae) results in
      the process of biological nitrogen fixation, playing a key role in global N
      cycling, and also bringing relevant contributions to the agriculture.
      Bradyrhizobium is considered as the ancestral of all nitrogen-fixing rhizobial
      species, probably originated in the tropics. The genus encompasses a variety of
      diverse bacteria, but the diversity captured in the analysis of the 16S rRNA is
      often low. In this study, we analyzed twelve Bradyrhizobium strains selected from
      previous studies performed by our group for showing high genetic diversity in
      relation to the described species. In addition to the 16S rRNA, five housekeeping
      genes (recA, atpD, glnII, gyrB and rpoB) were analyzed in the MLSA (multilocus
      sequence analysis) approach. Analysis of each gene and of the concatenated
      housekeeping genes captured a considerably higher level of genetic diversity,
      with indication of putative new species. The results highlight the high genetic
      variability associated with Bradyrhizobium microsymbionts of a variety of
      legumes. In addition, the MLSA approach has proved to represent a rapid and
      reliable method to be employed in phylogenetic and taxonomic studies, speeding
      the identification of the still poorly known diversity of nitrogen-fixing
      rhizobia in the tropics. 

PMID- 24031883
TI  - Detection of Wolbachia (Alphaproteobacteria: rickettsiales) in three species of
      terrestrial isopods (crustacea: isopoda: oniscidea) in Brazil.
AB  - Terrestrial isopods are widely infected with Wolbachia. However, little is known
      about the presence of bacteria in the Neotropical species. The objective of this
      study was to test the hypothesis of presence of Wolbachia infection in the native
      species of terrestrial isopods, Atlantoscia floridana and Circoniscus bezzii, and
      in the introduced species Burmoniscus meeusei. 

PMID- 24031884
TI  - Expression of phenazine biosynthetic genes during the arbuscular mycorrhizal
      symbiosis of Glomus intraradices.
AB  - To explore the molecular mechanisms that prevail during the establishment of the
      arbuscular mycorrhiza symbiosis involving the genus Glomus, we transcriptionally
      analysed spores of Glomus intraradices BE3 during early hyphal growth. Among 458
      transcripts initially identified as being expressed at presymbiotic stages, 20%
      of sequences had homology to previously characterized eukaryotic genes, 30% were
      homologous to fungal coding sequences, and 9% showed homology to previously
      characterized bacterial genes. Among them, GintPbr1a encodes a homolog to
      Phenazine Biosynthesis Regulator (Pbr) of Burkholderia cenocepacia, an
      pleiotropic regulatory protein that activates phenazine production through
      transcriptional activation of the protein D isochorismatase biosynthetic enzyme
      phzD (Ramos et al., 2010). Whereas GintPbr1a is expressed during the presymbiotic
      phase, the G. intraradices BE3 homolog of phzD (BGintphzD) is transcriptionally
      active at the time of the establishment of the arbuscular mycorrhizal symbiosis.
      DNA from isolated bacterial cultures found in spores of G. intraradices BE3
      confirmed that both BGintPbr1a and BGintphzD are present in the genome of its
      potential endosymbionts. Taken together, our results indicate that spores of G.
      intraradices BE3 express bacterial phenazine biosynthetic genes at the onset of
      the fungal-plant symbiotic interaction. 

PMID- 24031885
TI  - Rhinovirus detection using different PCR-based strategies.
AB  - Human rhinoviruses (HRVs) are the major cause of the common cold. HRVs were
      recently reclassified into the Enterovirus genus (HEV) in the Picornaviridae
      family. HRVs and other members of the HEV genus share many common features,
      including sense RNA genomes and partial nucleotide sequence identity. The aim of
      this study was to evaluate different HRV detection strategies. Samples from
      adults with acute respiratory infection (n = 291) who were treated in Sao Paulo
      Hospital (2001-2003) were tested using three assays. The first assay detected
      picornaviruses by RT-PCR and hybridization, the second detected rhinoviruses
      using RT-PCR/sequencing, and the third differentiated HRV from HEV using duplex
      semi-nested-RT-PCR. Analysis of the results obtained from the first two
      strategies revealed 83% concordance. Discordant samples were then evaluated by
      the third protocol, and 82% were negative. The picornavirus detection protocol
      was more sensitive but less specific than the rhinovirus detection protocols. The
      semi-nested protocol utilized in the present study was less sensitive and was not
      useful in differentiating HRV from HEV. Sequencing assays examining different
      genes would address the best strategy of confirming rhinovirus and enterovirus
      infections. 

PMID- 24031886
TI  - Correlation between ebv co-infection and HPV16 genome integrity in Tunisian
      cervical cancer patients.
AB  - Infection with high risk Human papillomavirus (HR-HPV) is necessary but not
      sufficient to cause cervical carcinoma. This study explored whether multiple HR
      HPV or coinfection with Epstein-Barr virus (EBV) influence the integration status
      of HPV16 genome. The presence and typing of HPV in a series of 125 cervical
      specimens were assessed by polymerase chain reaction (PCR) using the specific
      primers for the HPV L1 region. As for EBV infection, the viral EBNA1 gene was
      used for its detection through PCR amplification. Disruption of the HPV E2 gene
      was assessed by amplification of the entire E2 gene with single set of primers,
      while E2 transcripts were evaluated by a reverse transcription PCR method (RT
      PCR). The overall prevalence of HPVDNA was of 81.8% in cervical cancers versus
      26.9% in benign lesions. In HPV positive cases, HPV16 and HPV18 were the most
      prevalent types, followed by HPV types 33, 31. EBV EBNA1 prevalence was
      statistically more frequent in cervical carcinomas than in benign lesions (29.5%,
      vs 9.6%; P=0.01). No viral infection was detected in healthy control women. The
      uninterrupted E2 gene was correlated with the presence of E2 transcripts
      originating from the HPV episomal forms. It was observed that integration was
      more common in HPV18 and EBV coinfection. The presence of EBV caused a five-fold
      [OR= 5; CI= 1.15-21.8; P = 0.04] increase in the risk of HPV16 genome integration
      in the host genome. This study indicates that EBV infection is acting as a
      cofactor for induction of cervical cancer by favoring HPVDNA integration. 

PMID- 24031887
TI  - Virulence potential and antibiotic susceptibility pattern of motile aeromonads
      associated with freshwater ornamental fish culture systems: a possible threat to
      public health.
AB  - Aeromonas spp. are ubiquitous aquatic organisms, associated with multitude of
      diseases in several species of animals, including fishes and humans. In the
      present study, water samples from two ornamental fish culture systems were
      analyzed for the presence of Aeromonas. Nutrient agar was used for Aeromonas
      isolation, and colonies (60 No) were identified through biochemical
      characterization. Seven clusters could be generated based on phenotypic
      characters, analyzed by the programme NTSYSpc, Version 2.02i, and identified as:
      Aeromonas caviae (33.3%), A. jandaei (38.3%) and A. veronii biovar sobria
      (28.3%). The strains isolated produced highly active hydrolytic enzymes,
      haemolytic activity and slime formation in varying proportions. The isolates were
      also tested for the enterotoxin genes (act, alt and ast), haemolytic toxins (hlyA
      and aerA), involved in type 3 secretion system (TTSS: ascV, aexT, aopP, aopO,
      ascF-ascG, and aopH), and glycerophospholipid-cholesterol acyltransferase (gcat).
      All isolates were found to be associated with at least one virulent gene.
      Moreover, they were resistant to frequently used antibiotics for human
      infections. The study demonstrates the pathogenic potential of Aeromonas,
      associated with ornamental fish culture systems suggesting the emerging threat to
      public health. 

PMID- 24031888
TI  - Increase resistant rates and ESBL production between E. coli isolates causing
      urinary tract infection in young patients from Iran.
AB  - Emerging antimicrobial resistance rates and Extended-spectrum beta-lactamase
      producing Escherichia coli recovered from urinary tract infections (UTI) is an
      increasing problem in specific regions, limiting therapeutic options. One hundred
      E. coli isolates causing UTI in patients with age from 2 months to 12 years
      admitted at CMC in the period of April 2009 to March 2010 were tested for
      antibiotic susceptibility using the disk diffusion method. Surprisingly high
      resistance rates were recorded for E. coli against TMP/SMX (84%), cefalotin
      (66%), cefuroxime (50%), cefixime (50%) and ceftriaxone (45%). Antimicrobial
      susceptibility of E. coli isolates was followed by meropenem (98%), amikacin
      (95%), nitrofurantoin (91%) and gentamicin (68%). Extended spectrum beta
      lactamase production, was observed in 32% of community and 42% of nosocomial
      isolates. The results of this study and numerous observations regarding the
      increasing resistance to these antibiotics, in several countries, emphasize the
      need for local population-specific surveillance for guiding empirical therapy for
      UTI in children. 

PMID- 24031889
TI  - Antifungal activity of lectins against yeast of vaginal secretion.
AB  - Lectins are carbohydrate-binding proteins of non-imune origin. This group of
      proteins is distributed widely in nature and they have been found in viruses,
      microorganisms, plants and animals. Lectins of plants have been isolated and
      characterized according to their chemical, physical-chemical, structural and
      biological properties. Among their biological activities, we can stress its
      fungicidal action. It has been previously described the effect of the lectins
      Dviol, DRL, ConBr and LSL obtained from the seeds of leguminous plants on the
      growth of yeasts isolated from vaginal secretions. In the present work the
      experiments were carried out in microtiter plates and the results interpreted by
      both methods: visual observations and a microplate reader at 530nm. The lectin
      concentrations varied from 0.5 to 256MUg/mL, and the inoculum was established
      between 65-70% of trammitance. All yeast samples isolated from vaginal secretion
      were evaluated taxonomically, where were observed macroscopic and microscopic
      characteristics to each species. The LSL lectin did not demonstrate any
      antifungal activity to any isolate studied. The other lectins DRL, ConBr and
      DvioL, showed antifungal potential against yeast isolated from vaginal secretion.
      These findings offering offer a promising field of investigation to develop new
      therapeutic strategies against vaginal yeast infections, collaborating to improve
      women's health. 

PMID- 24031890
TI  - Occurrence of methicillin resistant Staphylococcus aureus (MRSA) among clinical
      samples in tehran-iran and its correlation with polymorphism of specific
      accessory gene regulator (AGR) groups.
AB  - Methicillin-Resistant Staphylococcus aureus (MRSA) is responsible for an
      increasing number of serious hospital and community acquired infections.
      Virulence gene expression in Staphylococcus aureus is orchestrated by regulators
      such as the accessory gene regulator (agr). Staphylococcal strains are divided
      into four major agr groups (agrI-IV) on the basis of agrD and agrC polymorphisms.
      The purpose of this study was to define the prevalence of MRSA strains in
      appointed Tehran's hospitals and then to define and compare the proportion of agr
      I, II, III, IV polymorphisms between MRSA and Methicillin Sensitive
      Staphylococcus aureus (MSSA) strains. A total of 235 isolates were evaluated by
      conventional antibiotic susceptibility tests and PCR for agr and mecA genes. 112
      strains were MRSA (47.5%) and the most prevalent agr specific group was agr I
      followed by agr III, agr II and agr IV, respectively. The prevalence of agr
      groups amongst MRSA and MSSA strains was not statistically significant (P>=0.05).
      This study suggests that agr I is not only the most prevalent agr type in MRSAs
      but also the most common one in Methicillin Sensitive Staphylococcus aureus
      (MSSA) strains in Iran. 

PMID- 24031891
TI  - Antimicrobial effects of allicin and ketoconazole on trichophyton rubrum under in
      vitro condition.
AB  - Dermatophytosis is caused by a group of pathogenic fungi namely, dermatophytes,
      is among the most prevalent infectious diseases worldwide. Azole drugs are widely
      used in the treatment of dermatomycosis, but can cause various side effects and
      drug resistance to the patients. Hence, for solving this problem can be used from
      the plant extract as alternative for chemical drugs. Allicin is a pure bioactive
      compound isolated from garlic was tested for its potential as a treatment of
      dermatomycosis in this study. This study evaluated the in vitro efficacy of pure
      allicin against ten isolates of Trichophyton rubrum and the MIC50 and MIC90
      ranged from 0.78-12.5 MUg/ml for allicin. The results revealed that the order of
      efficacy based on the MICs values, all isolates showed almost comparable response
      to allicin and ketoconazole except for some isolates, at 28  degrees C for both 7
      and 10 days incubation. Mann-Whitney test indicate that MICs at 7 days incubation
      was not observed a significant difference between the effects of allicin and
      ketoconazole (p > 0.05), but MICs at 10 days incubation, a significant difference
      was observed (p <= 0.05). On the other side, time kill studies revealed that
      allicin used its fungicidal activity within 12-24 h of management in vitro as
      well as ketoconazole. In conclusion, allicin showed very good potential as an
      antifungal compound against mycoses-causing dermatophytes, almost the same as the
      synthetic drug ketoconazole. Therefore, this antifungal agent appears to be
      effective, safe and suitable alternative for the treatment of dermatomycosis. 

PMID- 24031892
TI  - Evaluation of antimicrobial activity of extracts of Tibouchina candolleana
      (melastomataceae), isolated compounds and semi-synthetic derivatives against
      endodontic bacteria.
AB  - This work describes the phytochemical study of the extracts from aerial parts of
      Tibouchina candolleana as well as the evaluation of the antimicrobial activity of
      extracts, isolated compounds, and semi-synthetic derivatives of ursolic acid
      against endodontic bacteria. HRGC analysis of the n-hexane extract of T.
      candolleana allowed identification of beta-amyrin, alpha-amyrin, and beta
      sitosterol as major constituents. The triterpenes ursolic acid and oleanolic acid
      were isolated from the methylene chloride extract and identified. In addition,
      the flavonoids luteolin and genistein were isolated from the ethanol extract and
      identified. The antimicrobial activity was investigated via determination of the
      minimum inhibitory concentration (MIC) using the broth microdilution method.
      Amongst the isolated compounds, ursolic acid was the most effective against the
      selected endodontic bacteria. As for the semi-synthetic ursolic acid derivatives,
      only the methyl ester derivative potentiated the activity against Bacteroides
      fragilis. 

PMID- 24031893
TI  - Growth rate inhibition of phytopathogenic fungi by characterized chitosans.
AB  - The inhibitory effects of fifteen chitosans with different degrees of
      polymerization (DP) and different degrees of acetylation (FA) on the growth rates
      (GR) of four phytopathogenic fungi (Alternaria alternata, Botrytis cinerea,
      Penicillium expansum, and Rhizopus stolonifer) were examined using a 96-well
      microtiter plate and a microplate reader. The minimum inhibitory concentrations
      (MICs) of the chitosans ranged from 100 MUg *mL(-1) to 1,000 MUg *mL(-1)
      depending on the fungus tested and the DP and FA of the chitosan. The antifungal
      activity of the chitosans increased with decreasing FA. Chitosans with low FA and
      high DP showed the highest inhibitory activity against all four fungi. P.
      expansum and B. cinerea were relatively less susceptible while A. alternata and
      R. stolonifer were relatively more sensitive to the chitosan polymers. Scanning
      electron microscopy of fungi grown on culture media amended with chitosan
      revealed morphological changes. 

PMID- 24031894
TI  - Chlorhexidine: beta-cyclodextrin inhibits yeast growth by extraction of
      ergosterol.
AB  - Chlorhexidine (Cx) augmented with beta-cyclodextrin (beta-cd) inclusion
      compounds, termed Cx:beta-cd complexes, have been developed for use as antiseptic
      agents. The aim of this study was to examine the interactions of Cx:beta-cd
      complexes, prepared at different molecular ratios, with sterol and yeast
      membranes. The Minimal Inhibitory Concentration (MIC) against the yeast Candida
      albicans (C.a.) was determined for each complex; the MICs were found to range
      from 0.5 to 2 MUg/mL. To confirm the MIC data, quantitative analysis of viable
      cells was performed using trypan blue staining. Mechanistic characterization of
      the interactions that the Cx:beta-cd complexes have with the yeast membrane and
      assessment of membrane morphology following exposure to Cx:beta-cd complexes were
      performed using Sterol Quantification Method analysis (SQM) and scanning electron
      microscopy (SEM). SQM revealed that sterol extraction increased with increasing
      beta-cd concentrations (1.71 *10(3); 1.4 *10(3); 3.45 *10(3), and 3.74 *10(3) CFU
      for 1:1, 1:2, 1:3, and 1:4, respectively), likely as a consequence of membrane
      ergosterol solubilization. SEM images demonstrated that cell membrane damage is a
      visible and significant mechanism that contributes to the antimicrobial effects
      of Cx:beta-cd complexes. Cell disorganization increased significantly as the
      proportion of beta-cyclodextrin present in the complex increased. Morphology of
      cells exposed to complexes with 1:3 and 1:4 molar ratios of Cx:beta-cd were
      observed to have large aggregates mixed with yeast remains, representing more
      membrane disruption than that observed in cells treated with Cx alone. In
      conclusion, nanoaggregates of Cx:beta-cd complexes block yeast growth via
      ergosterol extraction, permeabilizing the membrane by creating cluster-like
      structures within the cell membrane, possibly due to high amounts of hydrogen
      bonding. 

PMID- 24031895
TI  - Applicability of the use of waste from different banana cultivars for the
      cultivation of the oyster mushroom.
AB  - The objective of this research was to evaluate the oyster mushroom Pleurotus
      ostreatus- (Jacq.: Fr.) Kumm. cultivation in substrates based on different
      combinations of wastes (leaf, pseudo-stem and pseudo-stem + leaf) and banana
      cultivars - Musa spp. (Thap Maeo, Prata AnaPelipita and Caipira) during 49 days.
      Organic matter loss in the substrate by action of the fungus was also evaluated
      during that period. It was verified that the pseudo-stem waste provided the best
      averages of biological efficiency among all cultivars tested and best rates were
      obtained by Thap Maeo (61.5%). The highest organic matter loss (OML) was obtained
      from pseudo-stem + leaf wastes (Prata Ana 78.6%; Thap Maeo - 67.6%; Pelipita -
      64.8%; Caipira - 60.6%). Therefore, the use of those wastes showed itself viable
      for P. ostreatus cultivation due to its availability and low cost, besides
      decreasing discards to environment. 

PMID- 24031896
TI  - Variability in the production of extracellular enzymes by entomopathogenic fungi
      grown on different substrates.
AB  - Entomopathogenic fungi are important controllers of pest-insects populations in
      agricultural production systems and in natural environment. These fungi have
      enzymatic machinery which involve since the recognition and adherence of spores
      in their hosts culminating with infection and death of these insects. The main
      objective of this study was to analyzed extracellular enzyme production of the
      fungi strains Beauveria bassiana, Metarhizium anisopliae and Paecilomyces sp when
      cultured on substrates. These fungi were grown in minimal media containing
      specific substrates for the analysis of different enzymes such as amylases,
      cellulases, esterases, lipases, proteases (gelatin and caseinase), pectinases and
      cuticles of Musca domestica larvae and adults. All the assays were performed with
      and without the presence of dextrose in the culture media. The quantification of
      enzyme activity was performed by the ratio of halo / colony (H/C) and the results
      subjected to variance analysis level of 5% (ANOVA) followed by post-Tukey test.
      All strains were positive for lipase and also they showed a high significant
      enzyme production for gelatin at concentrations of 4 and 1%. B. bassiana and
      Paecilomyces sp. were positive for amylase, pectinase and caseinase, and only
      Paecilomyces sp. showed cellulase activity. 

PMID- 24031897
TI  - Expression of virulence genes by Listeria monocytogenes J0161 in natural
      environment.
AB  - Majority of studies concerning the gene expression of Listeria monocytogenes have
      been done on pure culture states. Our objective was to study L.monocytogenes in a
      co-cultured state and to understand if microbes in their natural state of
      existence are different in their expression than that of the purely cultured lab
      grown forms. For a long period discussions have been on the expression of prfA,
      (which is a virulence gene regulator) in a mammalian host and its role in causing
      the switch from a saprophytic to pathogenic form of L.monocytogenes. We, in this
      paper for the first time report the expression of prfA and other virulence genes
      by L.monocytogenes under different extracellular conditions, and also as a pure
      culture biofilms, that is different from the previous reports. We also report
      that the expression of prfA seems to vary considerably when co-cultured with
      Bacillus subtilis. 

PMID- 24031898
TI  - Bioprospecting thermophiles for cellulase production: a review.
AB  - Most of the potential bioprospecting is currently related to the study of the
      extremophiles and their potential use in industrial processes. Recently microbial
      cellulases find applications in various industries and constitute a major group
      of industrial enzymes. Considerable amount of work has been done on microbial
      cellulases, especially with resurgence of interest in biomass ethanol production
      employing cellulases and use of cellulases in textile and paper industry. Most
      efficient method of lignocellulosic biomass hydrolysis is through enzymatic
      saccharification using cellulases. Significant information has also been gained
      about the physiology of thermophilic cellulases producers and process development
      for enzyme production and biomass saccharification. The review discusses the
      current knowledge on cellulase producing thermophilic microorganisms, their
      physiological adaptations and control of cellulase gene expression. It discusses
      the industrial applications of thermophilic cellulases, their cost of production
      and challenges in cellulase research especially in the area of improving process
      economics of enzyme production. 

PMID- 24031899
TI  - Challenges in shrimp aquaculture due to viral diseases: distribution and biology
      of the five major penaeid viruses and interventions to avoid viral incidence and
      dispersion.
AB  - SHRIMP AQUACULTURE HAS BEEN DRAMATICALLY AFFECTED BY MANY PATHOGENIC DISEASES,
      MAINLY CAUSED BY FIVE VIRUSES: IHHNV, YHV, TSV, WSSV, and IMNV. Here we provide a
      state-of-the-art overview of these shrimp viruses, with emphasis on distribution,
      pathology, morphology, and genomic organization, in addition to current
      diagnostic methods and intervention practices. 

PMID- 24031900
TI  - Biodegradation of petroleum hydrocarbons in hypersaline environments.
AB  - Literature on hydrocarbon degradation in extreme hypersaline media presents
      studies that point to a negative effect of salinity increase on
      hydrocarbonoclastic activity, while several others report an opposite tendency.
      Based on information available in the literature, we present a discussion on the
      reasons that justify these contrary results. Despite the fact that microbial
      ability to metabolize hydrocarbons is found in extreme hypersaline media, indeed
      some factors are critical for the occurrence of hydrocarbon degradation in such
      environments. How these factors affect hydrocarbon degradation and their
      implications for the assessment of hydrocarbon biodegradation in hypersaline
      environments are presented in this review. 

PMID- 24031901
TI  - A simple and reliable PCR-restriction fragment length polymorphism assay to
      identify Candida albicans and its closely related Candida dubliniensis.
AB  - Candida dubliniensis is an emerging pathogen capable of causing superficial as
      well as systemic infections. Due to its close similarity to C. albcians,
      conventional methods based on phenotypic traits are not always reliable in
      identification of C. dubliniensis. In this study, we developed a PCR-restriction
      fragment length polymorphism (RFLP) assay to identify and discriminate between
      the two closely related species. The D1/D2 region of 28S rDNA was amplified by
      PCR and enzymatically digested by ApaI and BsiEI respectively. PCR products of
      both species were digested into two fragments by ApaI, but those of other yeast
      species were undigested. BsiEI cut the PCR products of C. albicans into two
      fragments but not those of C. dubliniensis. Thus two species were differentiated.
      We evaluated 10 reference strains representing 10 yeast species, among which C.
      albicans and C. dubliniensis were successfully identified. A total of 56
      phenotypically characterized clinical isolates (42 C. albicans isolates and 14 C.
      dubliniensis isolates) were also investigated for intra-species variability. All
      tested isolates produced identical RFLP patterns to their respective reference
      strains except one initially misidentified isolate. Our method offers a simple,
      rapid and reliable molecular method for the identification of C. albicans and C.
      dubliniensis. 

PMID- 24031902
TI  - Occurrence of killer Candida glabrata clinical isolates.
AB  - In this work we characterized the occurrence of killer activity in 64 Candida
      glabrata clinical isolates under different conditions. We found that only 6.25 %
      of the clinical isolates tested were positive for killer activity against a
      Saccharomyces cerevisiae W303 sensitive strain. Sensitivity of killer activity to
      different values of pH and temperatures was analyzed. We found that the killer
      activity presented by all isolates was resistant to every pH and temperature
      tested, although optimal activity was found at a range of pH values from 4 to 7
      and at 37 degrees C. We did not observe extrachromosomal genetic elements
      associated with killer activity in any of the positive C. glabrata isolates. The
      killer effect was due to a decrease in viability and DNA fragmentation in
      sensitive yeast. 

PMID- 24031903
TI  - Subtyping of Chilean Methicillin-Resistant Staphylococcus aureus strains carrying
      the staphylococcal cassette chromosome mec type I.
AB  - The cassette chromosome mec (SCCmec) present in methicillin-resistant
      Staphylococcus aureus (MRSA) has two essential components, the ccr gene complex
      and the mec gene complex. Additionally, SCCmec has non-essential components
      called J regions which are used for MRSA subtyping. This study was performed to
      determine subtypes MRSA strains carrying SCCmec type I based on polymorphism of
      regions located downstream of the mecA gene. A total of 98 MRSA strains carrying
      SCCmec type I isolated from patients hospitalized at the County Hospital of
      Valdivia (Chile) between May 2007 and May 2008, were analyzed by multiplex PCR
      designed to amplify the mecA gene and 7 DNA hypervariable regions located around
      the mecA gene. MRSA strains were classified into seventeen genotypes accordingly
      to amplification patterns of DNA hypervariable regions. Five genotypes showed
      amplification patterns previously described. The remaining twelve genotypes
      showed new amplification patterns. Genotypes 18 and Genotype 19 were the most
      frequently detected. Regions HVR, Ins117 and pI258 stand out as being present in
      more than 60% of tested isolates. The acquisition of hypervariable regions by
      MRSA is a continuous horizontal transfer process through which the SCCmec have
      been preserved intact, or even may give rise to new types and subtypes of SCCmec.
      Therefore it is possible to infer that most MRSA strains isolated at the County
      Hospital of Valdivia (Chile) were originated from two local clones which
      correspond to Genotype 18 and Genotype 19. 

PMID- 24031904
TI  - Isolation of Microsporum gypseum in soil samples from different geographical
      regions of brazil, evaluation of the extracellular proteolytic enzymes activities
      (keratinase and elastase) and molecular sequencing of selected strains.
AB  - A survey of Microsporum gypseum was conducted in soil samples in different
      geographical regions of Brazil. The isolation of dermatophyte from soil samples
      was performed by hair baiting technique and the species were identified by
      morphology studies. We analyzed 692 soil samples and the recuperating rate was
      19.2%. The activities of keratinase and elastase were quantitatively performed in
      138 samples. The sequencing of the ITS region of rDNA was performed in
      representatives samples. M. gypseum isolates showed significant quantitative
      differences in the expression of both keratinase and elastase, but no significant
      correlation was observed between these enzymes. The sequencing of the
      representative samples revealed the presence of two teleomorphic species of M.
      gypseum (Arthroderma gypseum and A. incurvatum). The enzymatic activities may
      play an important role in the pathogenicity and a probable adaptation of this
      fungus to the animal parasitism. Using the phenotypical and molecular analysis,
      the Microsporum identification and their teleomorphic states will provide a
      useful and reliable identification system. 

PMID- 24031905
TI  - Evaluation of diagnostic methods for the detection of Helicobacter pylori in
      gastric biopsy specimens of dyspeptic patients.
AB  - Helicobacter pylori infects nearly 50% of the world's population. This
      microorganism is accepted as the most important agent of gastritis and as a risk
      factor for peptic ulcer disease and gastric adenocarcinoma. Currently many
      diagnostic methods exist for detecting H. pylori, however they all have
      limitations, thus it is recommend a combination of at least two methods. The aim
      of this study was to evaluate diagnostic methods, such as in-house urease test,
      culture and Polymerase Chain Reaction (PCR), for the detection of the H. pylori
      in gastric biopsy specimens of 144 dyspeptic patients, using as gold standard the
      association between histology and rapid urease test. According to the gold
      standard used in this study, 48 (33.3%) patients were infected with H. pylori,
      while 96 (66.7%) were classified as not infected. The in-house urease test and
      the PCR were the most sensitive methods (100%), followed by culture (85.4%).
      However, the inhouse urease test and the culture were the most specific (100%),
      followed by PCR (75%). In conclusion, this study showed that, in comparison with
      the combination of histology and rapid urease test, the in-house urease test and
      the PCR presented 100% of sensitivity in the diagnosis of gastric infection by H.
      pylori, while the in-house urease test and the culture reached 100% of
      specificity. These finding suggest that the combination of two or more methods
      may improve the accuracy of the H. pylori detection. 

PMID- 24031906
TI  - Occurrence of periodontal pathogens among patients with chronic periodontitis.
AB  - The aim of the present study was to evaluate the presence of the periodontal
      pathogens that form the red complex (Tannerella forsythia, Porphyromonas
      gingivalis and Treponema denticola) and Aggregatibacter actinomycetemcomitans in
      patients with chronic periodontitis. The sample consisted of 29 patients with a
      clinical and radiographic diagnosis of chronic periodontitis based on the
      criteria of the American Academy of Periodontology (3). Samples for
      microbiological analysis were collected from the four sites of greatest probing
      depth in each patient, totaling 116 samples. These samples were processed using
      conventional polymerase chain reaction, which achieved the following positive
      results: 46.6% for P. gingivalis, 41.4% for T. forsythia, 33.6% for T. denticola
      and 27.6% for A. actinomycetemcomitans. P. gingivalis and T. forsythia were more
      prevalent (p < 0.05) in periodontal pockets >= 8 mm. The combinations T.
      forsythia + P. gingivalis (23.2%) and T. forsythia + P. gingivalis + T. denticola
      (20.0%) were more frequent in sites with a probing depth >= 8 mm. Associations
      with the simultaneous presence of A. actinomycetemcomitans + P. gingivalis, A.
      actinomycetemcomitans + T. forsythia, P. gingivalis + T. forsythia and T.
      forsythia + T. denticola were statistically significant (p < 0.05). It was
      concluded that the red complex pathogens are related to chronic periodontitis,
      presenting a higher occurrence in deep periodontal pockets. Moreover, the
      simultaneous presence of these bacteria in deep sites suggests a symbiotic
      relationship between these virulent species, favoring, in this way, a further
      progression of periodontal disease. 

PMID- 24031907
TI  - Isolation of the first IMP-4 metallo-beta-lactamase producing Klebsiella
      pneumoniae in Tianjin, China.
AB  - This study shows for the first time the mechanism of carbapenem resistance of a
      Klebsiella pneumoniae clinical isolate TJ8 recovered from Tianjin Medical
      University General Hospital ,China. The modified Hodge test and EDTA synergy test
      were performed for the screening of carbapenemases and metallo-beta-lactamases
      (MBLs), respectively. Polymerase chain reactions and DNA sequencing confirmed
      that the strain carried IMP-4 metallo-beta-lactamase (MBL) , SHV-11 and TEM-1
      beta-lactamase. Class I integron was positive and gave a 3.0-kb PCR amplicon .IMP
      4 was located in Class I integron 5'CS. The gene determinants were organized in
      the order of bla IMP-4-orfII-orfIII.In all, the results show that IMP-4 MBL
      production caused the TJ8 resistance to carbapenems. 

PMID- 24031908
TI  - Carriage frequency, phenotypic and genotypic characteristics of Staphylococcus
      aureus isolated from dialysis and kidney tranplant patients at a hosptial in
      northern parana.
AB  - The objective of the present study was to determine the frequency of
      Staphylococcus aureus nasal carriage among dialysis and kidney transplant
      patients, to identify the antimicrobial resistance profile of these strains and
      to verify their genetic profiles with the RW3A primer. The study included 159
      individuals, comprising 111 dialysis and 48 kidney transplant patients. Of the 48
      transplant patients, 75% were positive for S. aureus, whereas 49% of the 111
      dialysis patients were carriers. Two samples yielded conflicting results for
      oxacillin sensitivity between the disk diffusion and minimum inhibitory
      concentration (MIC) assays: both were sensitive by the disk diffusion assay and
      resistant by MIC (4 MUg/ml). In the antibiogram by disk diffusion, ten samples
      were resistant to cefoxitin, among which eight were also resistant to oxacillin.
      The resistance of the ten samples to cefoxitin by the disk diffusion assay was
      confirmed by MIC. Of the ten oxacillin-resistant samples, eight harbored the mecA
      gene. All samples were sensitive to vancomycin, and most were resistant to
      penicillin and demonstrated high rates of resistance to the other antimicrobials
      tested. The samples from dialysis patients exhibited a more homogenous genetic
      profile. Among the samples with a high percent similarity, no correlation with
      sensitivity or resistance to oxacillin was observed. According to the results of
      this study, the implementation of prevention and control measures, such as
      increased restrictions on prescriptions for antimicrobial drugs and nasal
      decontamination prior to high-risk procedures, is recommended. 

PMID- 24031909
TI  - Detection of Mogibacterium timidum in subgingival biofilm of aggressive and non
      diabetic and diabetic chronic periodontitis patients.
AB  - The aim of the present study was to evaluate the frequency of detection of
      Mogibacterium timidum in subgingival samples of subjects with generalized
      aggressive periodontitis (GAgP) and uncontrolled diabetic and non-diabetic
      subjects with generalized chronic periodontitis (GChP). 48 patients with GAgP, 50
      non-diabetic and 39 uncontrolled (glycated hemoglobin >7%) type 2 diabetic
      subjects with GChP were enrolled in this study. Subgingival biofilm were
      collected from deep pockets (probing depth > 7 mm). After DNA extraction, M.
      timidum was detected by Nested Polymerase Chain Reaction and chi-square test was
      used to data analysis (p>0.05). There were no differences in the frequency of
      detection of M. timidum between subjects with GAgP (35%) and non-diabetic
      subjects with GChP (40%) (p>0.05). The frequency of detection of M. timidum was
      significantly higher in deep pockets of diabetic subjects with GChP (56%) when
      compared to GAgP (p<0.05), but similar to non-diabetic subjects with GChP
      (p>0.05). The frequency of detection of M. timidum was higher in subjects GChP
      presenting uncontrolled type 2 diabetes mellitus, when compared to GAgP subjects.

PMID- 24031910
TI  - Bactericidal antibiotic-phytochemical combinations against methicillin resistant
      Staphylococcus aureus.
AB  - Methicillin resistant Staphylococcus aureus (MRSA) infection is a global concern
      nowadays. Due to its multi-drug resistant nature, treatment with conventional
      antibiotics does not assure desired clinical outcomes. Therefore, there is a need
      to find new compounds and/or alternative methods to get arsenal against the
      pathogen. Combination therapies using conventional antibiotics and phytochemicals
      fulfill both requirements. In this study, the efficacy of different
      phytochemicals in combination with selected antibiotics was tested against 12
      strains of S. aureus (ATCC MRSA 43300, ATCC methicillin sensitive S. aureus or
      MSSA 29213 and 10 MRSA clinical strains collected from National University
      Hospital, Singapore). Out of the six phytochemicals used, tannic acid was
      synergistic with fusidic acid, minocycline, cefotaxime and rifampicin against
      most of strains tested and additive with ofloxacin and vancomycin. Quercetin
      showed synergism with minocycline, fusidic acid and rifampicin against most of
      the strains. Gallic acid ethyl ester showed additivity against all strains in
      combination with all antibiotics under investigation except with vancomycin where
      it showed indifference effect. Eugenol, menthone and caffeic acid showed
      indifference results against all strains in combination with all antibiotics.
      Interestingly, no antagonism was observed within these interactions. Based on the
      fractional inhibitory concentration indices, synergistic pairs were further
      examined by time-kill assays to confirm the accuracy and killing rate of the
      combinations over time. The two methods concurred with each other with 92%
      accuracy and the combinatory pairs were effective throughout the 24 hours of
      assay. The study suggests a possible incorporation of effective phytochemicals in
      combination therapies for MRSA infections. 

PMID- 24031911
TI  - Diphtheria Antibodies and T lymphocyte Counts in Patients Infected With HIV-1.
AB  - We assessed the IgG levels anti-diphtheria (D-Ab) and T cell counts (CD4+ and
      CD8+) in HIV-1 infected subjects undergoing or not highly active antiretroviral
      therapy (HAART). Approximately 70% of all HIV-1 patients were unprotected against
      diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated
      patients had higher D-Ab (geometric mean of 0.62 IU/ml) than HAART-patients
      (geometric mean of 0.39 IU/ml). The data indicated the necessity of keeping all
      HIV-1 patients up-to-date with their vaccination.

PMID- 24031912
TI  - Comparison of primers for RAPD-PCR from environmental isolates of Cryptococcus
      neoformans, Cryptococcus albidus and Cryptococcus laurentii complex.
AB  - Various organisms have been characterized by molecular methods, including fungi
      of the genus Cryptococcus. The purposes of this study were: to determine the
      discriminatory potential of the RAPD (Random Amplified Polymorphic DNA) primers,
      the pattern of similarity of the Cryptococcus species, and discuss their useful
      application in epidemiological studies. We analyzed 10 isolates of each
      specie/group: C. albidus, C. laurentii complex, C. neoformans var. grubii, all
      from environmental source, and two ATCC strains, C. neoformans var. grubii ATCC
      90112, and C. neoformans var. neoformans ATCC 28957 by RAPD-PCR using the primers
      CAV1, CAV2, ZAP19, ZAP20, OPB11 and SEQ6. The primers showed a good
      discriminatory power, revealing important differences between them and between
      species; the SEQ6 primer discriminated a larger number of isolates of three
      species. Isolates of C. laurentii showed greater genetic diversity than other
      species revealed by all six primers. Isolates of C. neoformans were more
      homogeneous. Only the primer CAV2 showed no amplification of DNA bands for C.
      albidus. It was concluded that the use of limited number of carefully selected
      primers allowed the discrimination of different isolates, and some primers (e.g.,
      CAV2 for C. albidus) may not to be applied to some species. 

PMID- 24031913
TI  - Antimicrobial activity of meta-alkoxyphenylcarbamates containing substituted N
      phenylpiperazine fragment.
AB  - In the present investigation, the basic esters of meta-alkoxyphenylcarbamic acid
      bearing variously substituted N-phenylpiperazine fragment were screened for their
      in vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli
      and Candida albicans, respectively. The most effective against Escherichia coli
      was found the compound 6d (MIC=195,3 MUg/mL) bearing simultaneously para-fluoro
      substituent at the 4-phenylpiperazin-1-yl core and meta-methoxy side chain in the
      lipophilic part of the molecule. From whole analyzed set of the molecules the
      substance 8e with propoxy side chain forming meta-alkoxyphenylcarbamoyl fragment
      and lipophilic, sterically bulky meta-trifluoromethyl group attached at N
      phenylpiperazine moiety was evaluated as the most active against Candida albicans
      (MIC=97,7 MUg/mL). On the contrary, all investigated structures were practically
      inactive against Staphylococcus aureus (MIC>1000 MUg/mL). 

PMID- 24031914
TI  - A prospective study on Aeromonas in outpatients with diarrhea in the central
      region of Rio Grande do Sul State.
AB  - Aeromonas spp. were identified in five (2,7%) of 182 diarrheal stool cultures, A.
      caviae was predominant, resistant mainly to ampicillin and cephalotin. This is
      the first study showing the presence of Aeromonas spp. in diarrheal stools of
      outpatients in the central region of Rio Grande do Sul State, Brazil. 

PMID- 24031915
TI  - Biofilm formation and binding specificities of CFA/I, CFA/II and CS2 adhesions of
      enterotoxigenic Escherichia coli and Cfae-R181A mutant.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains are leading causes of childhood
      diarrhea in developing countries. Adhesion is the first step in pathogenesis of
      ETEC infections and ETEC pili designated colonization factor antigens (CFAs) are
      believed to be important in the biofim formation, colonization and host cell
      adhesions. As a first step, we have determined the biofilm capability of ETEC
      expressing various types of pili (CFA/I, CfaE-R181A mutant/CfaE tip mutant,
      CFA/II and CS2). Further, enzyme-linked immunosorbent assay (ELISA) assay were
      developed to compare the binding specificity of CFA/I, CFA/II (CS1 - CS3) and CS2
      of ETEC, using extracted pili and piliated bacteria. CFA/II strain (E24377a) as
      well as extracted pili exhibited significantly higher binding both in biofilm and
      ELISA assays compared to non piliated wild type E24377a, CFA/I and CS2 strains.
      This indicates that co-expression of two or more CS2 in same strain is more
      efficient in increasing adherence. Significant decrease in binding specificity of
      DH5alphaF'lacI (q)/?cotD (CS2) strain and MC4100/pEU2124 (CfaE-R181A) mutant
      strain indicated the important contribution of tip proteins in adherence assays.
      However, CS2 tip mutant strain (DH5alphaF'lacI (q)/pEU5881) showed that this
      specific residue may not be important as adhesions in these strains. In summary,
      our data suggest that pili, their minor subunits are important for biofilm
      formation and adherence mechanisms. Overall, the functional reactivity of strains
      co expressing various antigens, particularly minor subunit antigen observed in
      this study suggest that fewer antibodies may be required to elicit immunity to
      ETEC expressing a wider array of related pili. 

PMID- 24031916
TI  - Nitrate reductase assay using sodium nitrate for rapid detection of multidrug
      resistant tuberculosis.
AB  - We validated the nitrate reductase assay (NRA) for the detection of multidrug
      resistant Mycobacterium tuberculosis (MDR-TB) using sodium nitrate (NaNO3) in
      replacement of potassium nitrate (KNO3) as nitrate source. NaNO3 is cheaper than
      KNO3 and has no restriction on use which facilitates the implementation of NRA to
      detect MDR-TB. 

PMID- 24031917
TI  - Preparation, characterization and in vitro antimicrobial activity of liposomal
      ceftazidime and cefepime against Pseudomonas aeruginosa strains.
AB  - Pseudomonas aeruginosa is an opportunistic microorganism with the ability to
      respond to a wide variety of environmental changes, exhibiting a high intrinsic
      resistance to a number of antimicrobial agents. This low susceptibility to
      antimicrobial substances is primarily due to the low permeability of its outer
      membrane, efflux mechanisms and the synthesis of enzymes that promote the
      degradation of these drugs. Cephalosporins, particularty ceftazidime and cefepime
      are effective against P. aeruginosa, however, its increasing resistance has
      limited the usage of these antibiotics. Encapsulating antimicrobial drugs into
      unilamellar liposomes is an approach that has been investigated in order to
      overcome microorganism resistance. In this study, antimicrobial activity of
      liposomal ceftazidime and cefepime against P. aeruginosa ATCC 27853 and P.
      aeruginosa SPM-1 was compared to that of the free drugs. Liposomal
      characterization included diameter, encapsulation efficiency and stability.
      Minimum Inhibitory Concentration (MIC) was determined for free and liposomal
      forms of both drugs. Minimum Bactericidal Concentration (MBC) was determined at
      concentrations 1, 2 and 4 times MIC. Average diameter of liposomes was 131.88 nm
      and encapsulation efficiency for cefepime and ceftazidime were 2.29% end 5.77%,
      respectively. Improved stability was obtained when liposome formulations were
      prepared with a 50% molar ratio for cholesterol in relation to the phospholipid.
      MIC for liposomal antibiotics for both drugs were 50% lower than that of the free
      drug, demonstrating that liposomal drug delivery systems may contribute to
      increase the antibacterial activity of these drugs. 

PMID- 24031918
TI  - In vitro biofilm forming potential of Streptococcus suis isolated from human and
      swine in China.
AB  - Streptococcus suis is a swine pathogen and also a zoonotic agent. The formation
      of biofilms allows S. suis to become persistent colonizers and resist clearance
      by the host immune system and antibiotics. In this study, biofilm forming
      potentials of various S. suis strains were characterized by confocal laser
      scanning microscopy (CLSM), scanning electron microscopy (SEM) and tissue culture
      plates stained with crystal violet. In addition, the effects of five
      antimicrobial agents on biofilm formation were assayed in this study. S. suis
      produced biofilms on smooth and rough surface. The nutritional contents including
      glucose and NaCl in the growth medium modulated biofilm formation. There was a
      significant difference in their biofilm-forming ability among all 46 S. suis
      strains. The biofilm-forming potential of S. suis serotype 9 was stronger than
      type 2 and all other types. However, biofilm formation was inhibited by five
      commonly used antimicrobial agents, penicillin, erythromycin, azithromycin,
      ciprofloxacin, and ofloxacin at subinhibitory concentrations, among which
      inhibition of ciprofloxacin and ofloxacin was stronger than that of other three
      antimicrobial agents.Our study provides a detailed analysis of biofilm formation
      potential in S. suis, which is a step towards understanding its role in
      pathogenesis, and eventually lead to a better understanding of how to eradicate
      S. suis growing as biofilms with antibiotic therapy. 

PMID- 24031919
TI  - Isolation and characterization of canine parvovirus type 2C (CPV-2C) from
      symptomatic puppies.
AB  - Canine parvovirus type 2 (CPV-2) is a leading cause of diarrhea in puppies in
      several parts of the world. In this study CPV-2 was detected and recovered from
      puppies showing clinical disease from Montevideo, Uruguay. Samples were processed
      and used to infect CRFK and MDCK cells in order to isolate the virus. Out of
      twelve, two samples were positive for CPV-2. A genomic region of 583 bp was
      amplified and the molecular characterization was performed by sequencing,
      phylogenetic analysis and Restriction Fragment Length Polymorphism (RFLP). Two
      isolated viruses (UY1 and UY2) were CPV-2c-like viruses. The comparison between
      the cytophatic effect (CPE) of CPV-2 (vaccinal virus) and CPV-2c (isolated virus)
      on primary canine cells cultures and on CRFK line cells, demonstrated that CPV-2c
      is less citopathogenic in CRFK than in primary cultures. Our study represents the
      first report on isolation and characterization of canine parvovirus type 2c (CPV
      2c) in cell cultures from South American dogs. 

PMID- 24031920
TI  - Genotypic and phenotypic detection of capsular polysaccharides in Staphylococcus
      aureus isolated from bovine intramammary infections in Argentina.
AB  - Staphylococcus aureus (n=157) isolated from intramammary infections in Argentine
      dairy areas were evaluated for presence of cap5 and cap8 loci. Isolates carrying
      cap5 and cap8 were serotyped using specific antisera. Sixty four percent of the
      isolates were genotyped as cap5 or cap8 and 50% of them expressed CP5 or 8. 

PMID- 24031921
TI  - Partial VP1 sequencing of Brazilian infectious bursal disease virus strains.
AB  - Infectious bursal disease virus (IBDV) is classified according to the
      antigenicity and virulence into classical virulent (cv), very virulent (vv), and
      antigenic variant strains. The molecular basis for the IBDV antigenic variation
      is well established and is associated to the capsid protein, VP2 (gene VP2 of
      segment A), whereas both VP2 and the RNA-dependent RNA polymerase, VP1 (gene VP1
      of segment B), have been correlated with the virulence. In this study, seventeen
      Brazilian IBDV samples previously characterized by the VP2 gene as cv (three) and
      vv (fourteen) strains were genetically and molecularly analyzed for their VP1
      gene. All of the strains kept with the same cv or vv classification except one
      sample, Br/03/DR. This sample was classified as vv by its VP2 gene, but it was
      most closely related to the cv strains by its VP1 partial sequence and phylogeny.
      Studies on the phylogeny of VP1 have suggested a possible reassortment event that
      originated the vvVP1. In this case, the sample carrying vvVP2 and cvVP1 could be
      a descendant of IBDV ancestors prior to the reassortment of vvVP1; alternatively,
      it could be the result of a genetic exchange between the segments of different
      strains or with a live attenuated vaccine. Nevertheless, this is the first report
      of natural genetic reassortment of IBDV in Brazil. 

PMID- 24031922
TI  - Detection of Genetic characterization of Porcine circovirus 2 (PCV2) in Brazilian
      wildlife boars.
AB  - A semi-intensive wildlife boars farm presented a clinical history of high
      mortality in 70 - 90 days-old pigs (> 50 %). Two 90 days-old animals with weight
      loss and wasting were necropsied and the samples tested for PCV2 by polymerase
      chain reaction (PCR). The genetic material of PCV2 was sequenced and classified
      into the PCV2a genotype together with PCV2 sequences obtained from samples of
      Poland, Brazil, Slovenia and Greece wild boars. 

PMID- 24031923
TI  - Molecular characterization of vanA-containing Enterococcus from migratory birds:
      song thrush (Turdus philomelos).
AB  - Vancomycin-resistant enterococci (VRE) were detected in two faecal samples (1.3%)
      of song thrush in Portugal. vanA isolates showed high level
      vancomycin/teicoplanin resistance, as well as resistance to ciprofloxacin,
      quinupristin-dalfopristin and cloranfenicol. Thrush can be a reservoir of VRE and
      transmit these resistant bacteria to other animals including humans. 

PMID- 24031924
TI  - Antimicrobial susceptibility of Clostridium perfringens isolated from piglets
      with or without diarrhea in Brazil.
AB  - The minimum inhibitory concentration (MIC) was determined for 13 antibiotics
      against Clostridium perfringens isolated from Brazilian piglets. The collection
      of isolates was performed in June to October 2010. All isolates were susceptible
      to amoxicillin and ceftiofur, whereas most were resistant to tetracycline and
      lincomycin. Avilamycin and narasin were more effective against isolates from non
      diarrheic than from diarrheic piglets. The other antimicrobials were less active
      in need of high concentrations to inhibit the growth of the C. perfringens type
      A. These results suggest the need for further studies evaluating molecular
      factors related to the antimicrobial resistance of C. perfringens. 

PMID- 24031925
TI  - First isolation of Mycobacterium avium subsp Paratuberculosis from commercial
      pasteurized milk in Argentina.
AB  - Mycobacterium avium subsp paratuberculosis was isolated from two out of seventy
      samples (2.86 %) of pasteurized and ultra-pasteurized milk. The isolates were
      positives to IS900 PCR and showed a C17 RFLP pattern, the most prevalent in
      Argentina. The present study is the first report of Mycobacterium avium subsp
      paratuberculosis culture from pasteurized milk in Argentina. 

PMID- 24031926
TI  - Molecular identification and thermoresistance to boiling of Nocardia farcinica
      and Nocardia cyriacigeorgica from bovine bulk tank milk.
AB  - Two strains of Nocardia spp. were isolated from bovine milk of two individual
      bulk tank. Molecular identification classified the strains as Nocardia farcinica
      and Nocardia cyriacigeorgica. The thermorresistance to boiling of the isolates
      was carried out and was observed bacterial growth after boiling. Our findings
      indicate the potential risk of pathogen transmission to humans through
      contaminated milk with Nocardia spp. 

PMID- 24031927
TI  - Production of pullulan by a thermotolerant aureobasidium pullulans strain in non
      stirred fed batch fermentation process.
AB  - Total 95 isolates of Aureobasidium pullulans were isolated from different flowers
      and leaves samples, out of which 11 thermotolerant strains produced pullulan. One
      thermotolerant non-melanin pullulan producing strain, designated as RG-5,
      produced highest pullulan (37.1+/-1.0 g/l) at 42(o)C, pH 5.5 in 48h of incubation
      with 3% sucrose and 0.5% ammonium sulphate in a non-stirred fed batch fermentor
      of 6 liters capacity. The two liters of initial volume of fermentation medium was
      further fed with the 2 liters in two successive batches at 5 h interval into the
      fermentor. The sterile air was supplied only for 10h at the rate of 0.5 vvm. 

PMID- 24031928
TI  - Medium optimization of protease production by Brevibacterium linens DSM 20158,
      using statistical approach.
AB  - Various cultivation parameters were optimized for the production of extra
      cellular protease by Brevibacterium linens DSM 20158 grown in solid state
      fermentation conditions using statistical approach. The cultivation variables
      were screened by the Plackett-Burman design and four significant variables
      (soybean meal, wheat bran, (NH4)2SO4 and inoculum size were further optimized via
      central composite design (CCD) using a response surface methodological approach.
      Using the optimal factors (soybean meal 12.0g, wheat bran 8.50g, (NH4)2SO4) 0.45g
      and inoculum size 3.50%), the rate of protease production was found to be twofold
      higher in the optimized medium as compared to the unoptimized reference medium. 

PMID- 24031929
TI  - Selection of thermophilic and thermotolerant fungi for the production of
      cellulases and xylanases under solid-state fermentation.
AB  - Twenty-seven thermophilic and thermotolerant fungal strains were isolated from
      soil, decaying organic matter and sugarcane piles based on their ability to grow
      at 45 degrees C on medium containing corn straw and cardboard as carbon sources.
      These fungi were identified in the genera Aspergillus, Thermomyces,
      Myceliophthora, Thermomucor and Candida. The majority of the isolated strains
      produced xylanase and cellulases under solid state fermentation (SSF). The
      highest cellulase and xylanase productions were obtained by the cultivation of
      the strains identified as Aspergillus fumigatus M.7.1 and Myceliophthora
      thermophila M.7.7. The enzymes from these strains exhibited maximum activity at
      pH 5.0 and at 60 and 70oC. The endo-glucanase from A. fumigatus was stable from
      40 degrees C to 65 degrees C and both endo-glucanase and xylanase from M.
      thermophila were stable in this temperature range when in absence of substrate.
      The enzymes were stable from pH 4.0 to 9.0. 

PMID- 24031930
TI  - Concomitant production of two proteases and alpha-amylase by a novel strain of
      Bacillus subtilis in a microprocessor controlled bioreactor.
AB  - We describe the simultaneous production of Bacillus subtilis based proteases and
      alpha amylase using a computer controlled laboratory scale 7.5 L batch
      bioreactor. The present strain is the first to be reported that concomitantly
      produces these two industrially important enzymes. The growth and sporulation of
      Bacillus subtilis was monitored and maximum production of alkaline protease and
      alpha amylase was found to coincide with maximum sporulation. Two types of
      proteases were detected in the fermentation broth; a neutral and an alkaline
      protease most active in a pH range of 7.0-8.0 and 8.0-10, respectively. Maximum
      production of proteases was observed at an incubation temperature of 37 degrees C
      while that of alpha amylase was observed at 40 degrees C. The optimum aeration
      and agitation levels for protease production were 0.6 L/L/min and 200rpm,
      respectively, and for alpha amylase were 0.6 L/L/min and 150 rpm. The kinetic
      parameters Yp/x and qp were also found to be significant at the given
      fermentation conditions. 

PMID- 24031931
TI  - Rapid screening of tannase producing microbes by using natural tannin.
AB  - Use of natural tannin in the screening of tannase producing microbes is really
      promising. The present work describes about the possibility and integrity of the
      newly formulated method over the previously reported methods. Tannin isolated
      from Terminalia belerica Roxb. (Bahera) was used to differentiate between
      tanninolytic and nontanninolytic microbes. The method is simple, sensitive and
      superior for the rapid screening and isolation of tannase-producing microbes. 

PMID- 24031932
TI  - Glucose(xylose) isomerase production by Streptomyces sp. CH7 grown on
      agricultural residues.
AB  - Streptomyces sp. CH7 was found to efficiently produce glucose(xylose) isomerase
      when grown on either xylan or agricultural residues. This strain produced a
      glucose(xylose) isomerase activity of roughly 1.8 U/mg of protein when it was
      grown in medium containing 1% xylose as a carbon source. Maximal enzymatic
      activities of about 5 and 3 U/mg were obtained when 1% xylan and 2.5% corn husks
      were used, respectively. The enzyme was purified from a mycelial extract to 16
      fold purity with only two consecutive column chromatography steps using Macro
      prep DEAE and Sephacryl-300, respectively. The approximate molecular weight of
      the purified enzyme is 170 kDa, and it has four identical subunits of 43.6 kDa as
      estimated by SDS-PAGE. Its K m values for glucose and xylose were found to be
      258.96 and 82.77 mM, respectively, and its V max values are 32.42 and 63.64
      MUM/min/mg, respectively. The purified enzyme is optimally active at 85 degrees C
      and pH 7.0. It is stable at pH 5.5-8.5 and at temperatures up to 60 degrees C
      after 30 min. These findings indicate that glucose(xylose) isomerase from
      Streptomyces sp. CH7 has the potential for industrial applications, especially
      for high-fructose syrup production and bioethanol fermentation from
      hemicellulosic hydrolysates by Saccharomyces cerevisiae. 

PMID- 24031933
TI  - Agro-industrial residues and starch for growth and co-production of
      polyhydroxyalkanoate copolymer and alpha-amylase by Bacillus sp. CFR-67.
AB  - Polyhydroxyalkanoates (PHA) and alpha-amylase (alpha-1,4 glucan-4
      glucanohydrolase, E.C. 3.2.1.1) were co-produced by Bacillus sp. CFR-67 using
      unhydrolysed corn starch as a substrate. Bacterial growth and polymer production
      were enhanced with the supplementation of hydrolysates of wheat bran (WBH) or
      rice bran (RBH) individually or in combination (5-20 g L(-1), based on weight of
      soluble substrates-SS). In batch cultivation, a mixture of WBH and RBH (1:1, 10 g
      L(-1) of SS) along with ammonium acetate (1.75 g L(-1)) and corn starch (30 g L(
      1)) produced maximum quantity of biomass (10 g L(-1)) and PHA (5.9 g L(-1)). The
      polymer thus produced was a copolymer of polyhydroxybutyrate-co-hydroxyvalerate
      of 95:5 to 90:10 mol%. Presence of WBH and corn starch (10-50 g L(-1)) in the
      medium enhanced fermentative yield of alpha-amylase (2-40 U mL(-1) min(-1)). The
      enzyme was active in a wide range of pH (4-9) and temperature (40-60 degrees C).
      This is the first report on simultaneous production of copolymer of bacterial PHA
      and alpha-amylase from unhydrolysed corn starch and agro-industrial residues as
      substrates. 

PMID- 24031934
TI  - Study on thermodynamics and adsorption kinetics of purified endoglucanase
      (CMCase) from Penicillium notatum NCIM NO-923 produced under mixed solid-state
      fermentation of waste cabbage and bagasse.
AB  - In the current study, one thermostable endoglucanase was purified from
      Penicillium notatum NCIM NO-923 through mixed solid state fermentation of waste
      cabbage and bagasse. The molecular weight of the purified enzyme was 55kDa as
      determined by SDS polyacrylamide gel electrophoresis (SDS-PAGE). The enzyme had
      low activation energy (Ea) of 36.39KJ mol(-1) for carboxymethyl cellulose
      hydrolysis and the enthalpy and entropy for irreversible inactivation was 87 kJ
      mol (-1) and 59.3 J mol (-1) K(-1) respectively. The enzyme was quite
      thermostable with a Tm value of 62.2 degrees C. The pKa1 and pKa2 of ionizable
      groups of the active sites were 2.5 and 5.3 respectively. Apparent Km, Vmax and
      Kcat of the enzyme were found to be 5.2 mg mL(-1), 80 U/gds and 322.4 sec(-1)
      respectively. The enzyme showed about 1.4 fold increased activity in presence of
      10mM MgSO4. Adsorption of endoglucanase on Avicel at wide pH range was studied at
      different temperatures. Langmuir type adsorption isotherm at 10 degrees C showed
      maximum adsorption strength of enzyme at pH 3.0, which was in a range of optimum
      pH of the enzyme. 

PMID- 24031935
TI  - Activity of disinfectants against foodborne pathogens in suspension and adhered
      to stainless steel surfaces.
AB  - The purpose of this study was to investigate and compare the efficacy of various
      disinfectants on planktonic cells and biofilm cells of Listeria monocytogenes,
      Staphylococcus aureus and Escherichia coli. Numbers of viable biofilm cells
      decreased after treatment with all tested disinfectants (iodine, biguanide,
      quaternary ammonium compounds, peracetic acid and sodium hypochlorite). Sodium
      hypochlorite was the most effective disinfectant against biofilm cells, while
      biguanide was the least effective. Scanning electron microscopy observations
      revealed that cells adhered on stainless steel surface after treatment with the
      disinfectants. No viable planktonic cells were observed after treatment with the
      same disinfectants. Based on our findings, we concluded that biofilm cells might
      be more resistant to disinfectants than plancktonic cells. 

PMID- 24031936
TI  - Combination of Origanum vulgare L. essential oil and lactic acid to inhibit
      Staphylococcus aureus in meat broth and meat model.
AB  - This study assessed the occurrence of an enhancing inhibitory effect of the
      combined application of Origanum vulgare L. essential oil and lactic acid against
      Staphylococcus aureus by the determination of Fractional Inhibitory Concentration
      (FIC) index and cell viability in meat broth and meat model. Minimum Inhibitory
      Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of the oil was
      0.6 and 1.25 uL.mL(-1), respectively. Lactic acid showed MIC and MBC of 2.5 and
      5uL.mL(-1), respectively. FIC indices of the combined application of the oil and
      lactic acid were 0.5 showing a synergic interaction. The essential oil and lactic
      acid showed similar (p>0.05) anti-S. aureus effect in meat broth over 96 h of
      exposure. Treatment with essential oil or lactic acid presented a smaller anti
      staphylococcal effect in meat in comparison to meat broth. No significant
      difference (p>0.05) was found for the microbial counts in meat treated with each
      antimicrobial alone or in mixture. These results could arise as an interesting
      approach for the improvement of food preservation using more natural procedures,
      considering the current demand of consumer and sensory quality of foods. 

PMID- 24031937
TI  - Bacteriophage amplification assay for detection of Listeria spp. using virucidal
      laser treatment.
AB  - A protocol for the bacteriophage amplification technique was developed for
      quantitative detection of viable Listeria monocytogenes cells using the A511
      listeriophage with plaque formation as the end-point assay. Laser and toluidine
      blue O (TBO) were employed as selective virucidal treatment for destruction of
      exogenous bacteriophage. Laser and TBO can bring a total reduction in titer phage
      (ca. 10(8) pfu/mL) without affecting the viability of L. monocytogenes cells.
      Artificially inoculated skimmed milk revealed mean populations of the bacteria as
      low as between 13 cfu/mL (1.11 log cfu/mL), after a 10-h assay duration.
      Virucidal laser treatment demonstrated better protection of Listeria cells than
      the other agents previously tested. The protocol was faster and easier to perform
      than standard procedures. This protocol constitutes an alternative for rapid,
      sensitive and quantitative detection of L. monocytogenes. 

PMID- 24031938
TI  - Pathogenic variation in isolates of Pseudomonas causing the brown blotch of
      cultivated mushroom, Agaricus bisporus.
AB  - Twenty seven bacterial isolates were isolated from superficial brown
      discolorations on the caps of cultivated Agaricus bisporus. After White Line
      Assay (WLA) and the assist of Biolog computer-identification system, isolates
      were divided into groups: (I) comprised ninteen bacterial isolates that
      positively responded to a Pseudomonas "reactans" reference strain (NCPPB1311) in
      WLA and were identified as Pseudomonas tolaasii, (II) comprised two isolates
      which were WLA+ towards the reference strain (JCM21583) of P. tolaasii and were
      proposed to be P. "reactans". The third group comprised six isolates, two of
      which weakly responded to the strain of P. tolaasii and were identified as P.
      gingeri whereas the other four were WLA-and identified as P. fluorescens (three
      isolates) and P. marginalis (one isolate). Isolates of P. tolaasii showed high
      aggressiveness compared with those of P. "reactans" in pathogenicity tests. Cubes
      of 1 cm(3) of A. bisporus turned brown and decreased in size when were inoculated
      with 10 ul of P. tolaasii suspension containing 10(8) CFU ml(-1), whereas a
      similar concentration of P. "reactans" caused only light browning. Fifty ul of
      the same concentration of P. tolaasii isolates gave typical brown blotch symptoms
      on fresh mushroom sporophores whereas the two P. "reactans" isolates caused
      superficial light discoloration only after inoculation with 100 ul of the same
      concentration. Mixture from both bacterial suspensions increased the brown areas
      formed on the pileus. This is the first pathogenicity report of P. tolasii and P.
      "reactans" isolated from cultivated A. bisporus in Egypt. 

PMID- 24031939
TI  - Inhibitory effect of essential oils against Lactobacillus rhamnosus and starter
      culture in fermented milk during its shelf-life period.
AB  - The use of essential oils in foods has attracted great interest, due to their
      antagonistic action against pathogenic microorganisms. However, this action is
      undesirable for probiotic foods, as products containing Lactobacillus rhamnosus.
      The aim of the present study was to measure the sensitivity profile of L.
      rhamnosus and a yogurt starter culture in fermented milk, upon addition of
      increasing concentrations of cinnamon, clove and mint essential oils. Essential
      oils were prepared by steam distillation, and chemically characterised by gas
      chromatography-mass spectrometry (GC-MS) and determination of density. Survival
      curves were obtained from counts of L. rhamnosus and the starter culture (alone
      and in combination), upon addition of 0.04% essential oils. In parallel,
      titratable acidity was monitored over 28 experimental days. Minimum inhibitory
      concentration values, obtained using the microdilution method in Brain Heart
      Infusion medium, were 0.025, 0.2 and 0.4% for cinnamon, clove and mint essential
      oils, respectively. Cinnamon essential oil had the highest antimicrobial
      activity, especially against the starter culture, interfering with lactic acid
      production. Although viable cell counts of L. rhamnosus were lower following
      treatment with all 3 essential oils, relative to controls, these results were not
      statistically significant; in addition, cell counts remained greater than the
      minimum count of 10(8)CFU/mL required for a product to be considered a probiotic.
      Thus, although use of cinnamon essential oil in yogurt makes starter culture
      fermentation unfeasible, it does not prevent the application of L. rhamnosus to
      probiotic fermented milk. Furthermore, clove and mint essential oil caused
      sublethal stress to L. rhamnosus. 

PMID- 24031940
TI  - Increase of stress resistance in Lactococcus lactis via a novel food-grade vector
      expressing a shsp gene from Streptococcus thermophilus.
AB  - The effects of the expression of a small heat shock protein (shsp) gene from
      Streptococcus thermophilus on stress resistance in Lactococcus lactis under
      different environmental stresses were investigated in this study. pMG36e-shsp, an
      expression vector, was first constructed by inserting a shsp open reading frame
      (ORF) cloned from S. thermophilus strain St-QC into pMG36e. Then, a food-grade
      expression vector, pMG-shsp, was generated by deleting the erythromycin
      resistance gene from pMG36e-shsp. The transformation rate of pMG-shsp was
      comparable to that of pMG36e-shsp when each of these two vectors was introduced
      into L. lactis. These results demonstrated that the shsp ORF could successfully
      used as a food-grade selection marker in both pMG-shsp and pMG36e-shsp.
      Furthermore, the growth characteristics were almost the same between L. lactis
      ML23 transformants harboring pMG36e or pMG-shsp. The survival rate of L. lactis
      ML23 expressing the shsp ORF were increased to 0.032%, 0.006%, 0.0027%, 0.03%,
      and 0.16% under the following environmental stresses: heat, acid, ethanol, bile
      salt and H2O2, respectively. These results indicated that the expression of the
      shsp gene in the food-grade vector pMG-shsp conferred resistance to environmental
      stresses without affecting the growth characteristics of L. lactis ML23. 

PMID- 24031941
TI  - Diversity of leaf endophytic fungi in mangrove plants of northeast Brazil.
AB  - With the aim of increasing the knowledge about endophytic fungi, a group of
      microorganisms with high biotechnological potential and a valuable source of
      useful metabolites, a survey in leaves of mangrove plants (Avicennia schaueriana,
      Laguncularia racemosa, and Rhizophora mangle) was performed at the Itamaraca
      Island, PE, Brazil. Leaves were collected, during two seasons, dry and rainy,
      superficially sterilized and fragments maintained in Petri dishes with Potato
      dextrose agar (PDA) at 28(o) +/- 2(o) C until isolation of the fungi. Fourty taxa
      were isolated: 25 species representing 19 genera and 15 morphotypes determined as
      Mycelia sterilia. Leaves of L. racemosa hosted the highest number of colony
      forming units (CFU) and taxa. Guignardia sp. and Colletotrichum gloeosporioides
      were the most frequently isolated, while Glomerella cingulata was the only
      species found in association with the three host plants. The proportional
      importance of each fungus differed among hosts. The similarity of fungi species
      between the two seasons reached only 4.2%, and that between the hosts was also
      low, with the maximum (A. schaueriana x L. racemosa) reaching 24.2%.
      Sphaerosporium, as well as Chloridium virescens var. virescens, Microsphaeropsis
      arundinis, Penicillium pinophilum, Periconia cambrensis, Phoma herbarum, P.
      diachenii, P. obscurans, Sordaria prolifica and Torula elisii are reported for
      the first time as endophytic in tropical regions. 

PMID- 24031942
TI  - Chemical characterization of bioactive compounds from the endophytic fungus
      Diaporthe helianthi isolated from Luehea divaricata.
AB  - Endophytic microorganisms, defined as fungi or bacteria that colonize the
      interior of plants without causing any immediate negative effects or damages,
      have reciprocal relationships with host plants. In some cases their presence is
      beneficial to the host due to the synthesis of bioactive compounds, among which
      several alcohols, esters, ketones and others that may react with other compounds
      and may be lethal to pathogenic microorganisms. Diaporthe helianthi (Phomopsis
      helianthi in its anamorphic phase) is available worldwide, especially in Europe,
      Asia and America. Isolated in Europe as an agent of the sunflower stem cancer, it
      has also been endophytically isolated from tropical and temperate plants. A D.
      helianthi strain isolated from Luehea divaricata has been employed in current
      research. An investigation of the secondary metabolite from D. helianthi by CC
      and NMR of (1)H and (13)C yielded the separation of 10 fractions and the
      identification of the phenolic compound 2(-4 hydroxyphenyl)-ethanol (Tyrosol).
      Its antimicrobial reaction was tested and the ensuing antagonistic effects on the
      human pathogenic bacteria Enterococcus hirae, Escherichia coli, Micrococcus
      luteus, Salmonella typhi, Staphylococcus aureus, phytopathogenic Xanthomonas asc.
      phaseoli and phytopathogenic fungi were demonstrated. Results show that bioactive
      compounds and Tyrosol produced by D. helianthi have a biotechnological potential.

PMID- 24031943
TI  - Bacterial exopolysaccharide and biofilm formation stimulate chickpea growth and
      soil aggregation under salt stress.
AB  - To compensate for stress imposed by salinity, biofilm formation and
      exopolysaccharide production are significant strategies of salt tolerant bacteria
      to assist metabolism. We hypothesized that two previously isolated salt-tolerant
      strains Halomonas variabilis (HT1) and Planococcus rifietoensis (RT4) have an
      ability to improve plant growth, These strains can form biofilm and accumulate
      exopolysacharides at increasing salt stress. These results showed that bacteria
      might be involved in developing microbial communities under salt stress and
      helpful in colonizing of bacterial strains to plant roots and soil particles.
      Eventually, it can add to the plant growth and soil structure. We investigated
      the comparative effect of exopolysacharide and biofilm formation in two bacterial
      strains Halomonas variabilis (HT1) and Planococcus rifietoensis (RT4) in response
      to varying salt stress. We found that biofilm formation and exopolysaccharide
      accumulation increased at higher salinity. To check the effect of bacterial
      inoculation on the plant (Cicer arietinum Var. CM-98) growth and soil
      aggregation, pot experiment was conducted by growing seedlings under salt stress.
      Inoculation of both strains increased plant growth at elevated salt stress.
      Weight of soil aggregates attached with roots and present in soil were added at
      higher salt concentrations compared to untreated controls. Soil aggregation was
      higher at plant roots under salinity. These results suggest the feasibility of
      using above strains in improving plant growth and soil fertility under salinity. 

PMID- 24031944
TI  - Metabolic networks and bioenergetics of Aurantiochytrium sp. B-072 during storage
      lipid formation.
AB  - Baffled shake flask cultivation of Aurantiochytrium sp. B-072 was carried out at
      in a glucose-monosodium glutamate mineral medium at different C/N-ratios (30-165)
      with glucose fixed at 90 g/L. With increasing C/N-ratio, a modest increase in
      lipid content (60 to 73 % w/w) was observed whereas fat-free biomass decreased
      but overall biomass showed little variation. FA-profiles were not affected to a
      large extent by C/N-ratio and absolute docosahexaenoic (DHA)-levels fell in
      narrow range (5-6 g/L). However at C/N > 64 a rapid decrease in lipid synthetic
      rate and/or incomplete glucose utilization occurred. Glucose and FA-fluxes based
      on fat-free biomass peaked at a C/N ratio of 56. This condition was chosen for
      calculation of the redox balance (NAD(P)H) and energy (ATP) requirement and to
      estimate the in vivo P/O ratio during the main period of fatty acid biosynthesis.
      Several models with different routes for NADPH, acetyl-CoA formation and re
      oxidation of OAA formed via ATP-citrate lyase were considered as these influence
      the redox- and energy balance. As an example, using a commonly shown scheme
      whereby NADPH is supplied by a cytosolic "transhydrogenase cycle" (pyruvate-OAA
      malate-pyruvate) and OAA formed by ATP-citrate lyase is recycled via import into
      the mitochondria as malate, the calculated NADPH-requirement amounted to 5.5 with
      an ATP-demand of 10.5 mmol/(g fat-free biomass x h) and an in vivo P/O-ratio (not
      including non-growth associated maintenance) of 1.6. The lowest ATP requirement
      is found when acetyl-CoA would be transported directly from the mitochondria to
      the cytosol by carnitine acetyltransferase. Assay of some enzymes critical for
      NADPH supply indicates that activity of glucose-6-phosphate dehydrogenase, the
      first enzyme in the HMP pathway, is far insufficient for the required NADPH-flux
      and malic enzyme must be a major source. Activity of the latter (ca. 300 mU/mg
      protein) far exceeds that in oleaginous fungi and yeast. 

PMID- 24031945
TI  - Oxygen limitation favors the production of protein with antimicrobial activity in
      Pseudoalteromonas sp.
AB  - This study examined the effect of dissolved oxygen concentration on the
      production of biomass and metabolites with antimicrobial activity of
      Pseudoalteromonas sp cultured at 0, 150, 250, or 450 revolutions per minute (rev.
      min(-1)). Dissolved oxygen (D.O) was monitored during the fermentation process,
      biomass was quantified by dry weight, and antimicrobial activity was assessed
      using the disk diffusion method. The bacterium Pseudoalteromonas reached similar
      concentration of biomass under all experimental agitation conditions, whereas
      antimicrobial activity was detected at 0 and 150 rev. min(-1) registering 0% and
      12% of D.O respectively corresponding to microaerophilic conditions. Antibiotic
      activity was severely diminished when D.O was above 20% of saturation; this
      corresponded to 250 or 450 rev. min(-1). SDS-PAGE electrophoresis revealed a
      protein with a molecular weight of approximately 80 kilodaltons (kDa) with
      antimicrobial activity. Pseudoalteromonas is capable of growing under oxic and
      microaerophilic conditions but the metabolites with antimicrobial activity are
      induced under microaerophilic conditions. The current opinion is that
      Pseudoalteromonas are aerobic organisms; we provide additional information on the
      amount of dissolved oxygen during the fermentation process and its effect on
      antimicrobial activity. 

PMID- 24031946
TI  - Amylase production by endophytic fungi Cylindrocephalumsp. isolated from
      medicinal plant Alpinia calcarata (Haw.) Roscoe.
AB  - Amylases are among the most important enzymes used in modern biotechnology
      particularly in the process involving starch hydrolysis. Fungal amylase has large
      applications in food and pharmaceutical industries. Considering these facts,
      endophytic fungi isolated from the plant Alpinia calcarata (Haw.) Roscoe were
      screened for amylolytic activity on glucose yeast extract peptone agar (GYP)
      medium. Among thirty isolates of endophytic fungi, isolate number seven
      identified as Cylindrocephalum sp. (Ac-7) showed highest amylolytic activity and
      was taken for further study. Influence of various physical and chemical factors
      such as pH, temperature, carbon and nitrogen sources on amylase production in
      liquid media were studied. The maximal amylase production was found to be at
      30(o)C and at pH 7.0 of the growth medium. Among the various carbon and nitrogen
      sources tested, maltose at 1.5% and Sodium nitrate at 0.3% respectively gave
      optimum amylase production. 

PMID- 24031947
TI  - Genetic transformation with the gfp gene of Colletotrichum gloeosporioides
      isolates from coffee with blister spot.
AB  - Blister spot (Colletotrichum gloeosporioides) is now widespread in most coffee
      producing states of Brazil, becoming a limiting factor for production. The lack
      of data relating to the reproduction of typical symptoms (light green, oily
      patches) leaves a gap within the pathosystem, forcing the search for new
      methodologies for monitoring the disease. Monitoring of genetically modified
      organisms has proven to be an effective tool in understanding the host * pathogen
      interactions. Thus, the present study was carried out to evaluate the
      effectiveness of two systems of genetic transformation in obtaining mutants using
      the gfp reporter gene. Using the two transformation systems (PEG and
      electroporation) revealed the efficiency of both, confirmed by fluorescence
      microscopy and resistance to the antibiotic hygromycin-B, when incorporated into
      the culture medium. The fungus maintained its cultural and morphological
      characteristics when compared to wild strains. When inoculated on coffee
      seedlings, it was found that the pathogenicity of the processed isolates had not
      changed. 

PMID- 24031948
TI  - Production of gaba (gamma - Aminobutyric acid) by microorganisms: a review.
AB  - GABA (gamma-aminobutyric acid) is a four carbon non-protein amino acid that is
      widely distributed in plants, animals and microorganisms. As a metabolic product
      of plants and microorganisms produced by the decarboxylation of glutamic acid,
      GABA functions as an inhibitory neurotransmitter in the brain that directly
      affects the personality and the stress management. A wide range of traditional
      foods produced by microbial fermentation contain GABA, in which GABA is safe and
      eco-friendly, and also has the possibility of providing new health-benefited
      products enriched with GABA. Synthesis of GABA is catalyzed by glutamate
      decarboxylase, therefore, the optimal fermentation condition is mainly based on
      the biochemical properties of the enzyme. Major GABA producing microorganisms are
      lactic acid bacteria (LAB), which make food spoilage pathogens unable to grow and
      act as probiotics in the gastrointestinal tract. The major factors affecting the
      production of GABA by microbial fermentation are temperature, pH, fermentation
      time and different media additives, therefore, these factors are summarized to
      provide the most up-dated information for effective GABA synthesis. There has
      been a huge accumulation of knowledge on GABA application for human health
      accompanying with a demand on natural GABA supply. Only the GABA production by
      microorganisms can fulfill the demand with GABA-enriched health beneficial foods.

PMID- 24031949
TI  - Microbial diversity in Brazilian mangrove sediments - a mini review.
AB  - The importance and protection of mangrove ecosystems has been recognized in
      Brazilian Federal law since 1965. Being protected in law, however, has not always
      guaranteed their protection in practice. Mangroves are found in coastal and
      estuarine locations, which are prime real estate for the growth of cities, ports
      and other economic activities important for Brazilian development. In this mini
      review we introduce what mangroves are and why they are so important. We give a
      brief overview of the microbial diversity found in mangrove sediments and then
      focus on diversity studies from Brazilian mangroves. We highlight the breadth and
      depth of knowledge about mangrove microbial communities gained from studying
      Brazilian mangroves. We report on the exciting findings of molecular microbial
      ecology methods that have been very successfully applied to study bacterial
      communities. We note that there have been fewer studies that focus on fungal
      communities and that fungal diversity studies deserve more attention. The review
      ends with a look at how a combination of new molecular biology methods and
      isolation studies are being developed to monitor and conserve mangrove ecosystems
      and their associated microbial communities. These recent studies are having a
      global impact and we hope they will help to protect and re-establish mangrove
      ecosystems. 

PMID- 24031950
TI  - Microbicide activity of clove essential oil (Eugenia caryophyllata).
AB  - Clove essential oil, used as an antiseptic in oral infections, inhibits Gram
      negative and Gram-positive bacteria as well as yeast. The influence of clove
      essential oil concentration, temperature and organic matter, in the antimicrobial
      activity of clove essential oil, was studied in this paper, through the
      determination of bacterial death kinetics. Escherichia coli, Staphylococcus
      aureus and Pseudomonas aeruginosa were the microorganisms selected for a
      biological test. To determine the temperature effect, they were assayed at 21
      degrees  and 37 degrees  C. The concentration coefficient was determined with
      0.4%, and 0.2% of essential oil. The influence of the presence of organic matter
      was determined with 0.4% of essential oil. The results obtained demonstrated that
      Escherichia coli were more sensitive even though the essential oil exerted a
      satisfactory action in three cases. In the three microbial species, 0.4% of
      essential oil at 21 degrees  C have reduced the bacterial population in 5
      logarithmic orders. Organic matter reduces the antibacterial activity even though
      the bactericide efficacy was not lost. Clove essential oil can be considered as a
      potential antimicrobial agent for external use. 

PMID- 24031951
TI  - Work of adhesion of dairy products on stainless steel surface.
AB  - The adhesion of the solids presents in food can difficult the process of surface
      cleaning and promotes the bacterial adhesion process and can trigger health
      problems. In our study, we used UHT whole milk, chocolate based milk and infant
      formula to evaluate the adhesion of Enterobacter sakazakii on stainless steel
      coupons, and we determine the work of adhesion by measuring the contact angle as
      well as measured the interfacial tension of the samples. In addition we evaluated
      the hydrophobicity of stainless steel after pre-conditioning with milk samples
      mentioned. E. sakazakii was able to adhere to stainless steel in large numbers in
      the presence of dairy products. The chocolate based milk obtained the lower
      contact angle with stainless steel surface, higher interfacial tension and
      consequently higher adhesion work. It was verified a tendency of decreasing the
      interfacial tension as a function of the increasing of protein content. The
      preconditioning of the stainless steel coupons with milk samples changed the
      hydrophobic characteristics of the surfaces and became them hydrophilic.
      Therefore, variations in the composition of the milk products affect parameters
      important that can influence the procedure of hygiene in surface used in food
      industry. 

PMID- 24031952
TI  - Efficacy evaluation of some antibiotics against syrian brucella spp isolates, in
      vitro.
AB  - Brucellosis is an endemic zoonosis in Syria, affecting large numbers of animals
      and there are an increasing number of cases in humans. The aim of this study is
      to investigate the in vitro efficacy of various traditional and new antibiotics
      against 89 Brucella isolates (isolated from domestic animals) collected from
      different Syrian regions. Minimum inhibitory concentrations (MICs) of seventeen
      antibiotics were determined. Ciprofloxacin and ofloxacin were the most effective
      antibiotics, whereas sparfloxacin, levofloxacin, doxycycline and tetracycline had
      a moderate activity. In contrast, moxifloxacin and rifampicin had a low activity,
      while streptomycin, spiramycin and cephalosporines were ineffective. As a result,
      we come to the conclusion that a combination between one effective quinolone and
      doxycycline has a good efficacy against Brucella. Further in vivo studies are
      necessary to support this suggestion. 

PMID- 24031953
TI  - Imipenem-resistant Acinetobacter baumannii carrying the ISAba1-bla OXA-23,51 and
      ISAba1-bla ADC-7 genes in Monteria, Colombia.
AB  - The purpose of this study was to identify the genes coding for resistance to
      ceftazidime and imipenem and describe the molecular epidemiology of A. baumannii
      strains isolated from a clinical center in Colombia. Twenty isolates of imipenem
      resistant A. baumannii from an equal number of patients with nosocomial
      infections were obtained. Primers were used to amplify genes bla IMP, bla VIM,
      bla OXA-23, bla OXA-24, bla OXA-58, bla OXA-51 and bla ADC-7. To detect insertion
      sequences ISAba1/bla OXA-23, ISAba1/bla OXA-51 and ISAba1/bla ADC-7, mapping by
      PCR using combinations of reverse primers ISAba1 and reverse primers of bla OXA
      23, bla OXA-51 and bla ADC-7 were used. The amplification products were purified
      and cloned into PCR 2.1-TOPO vector and transformed into chemically competent
      Escherichia coli TOP10. These amplicons were then sequenced. PFGE was performed
      on DNA of A. baumannii isolates digested with ApaI. Results. The DNA profiles
      obtained included 9 clusters with, four 2-7 isolates per profile, and 5 single
      isolate profiles. Of the 20 isolates resistant to imipenem, 15 carried bla OXA-23
      gene, 4 contained ISAba1 upstream of bla OXA-51 gene, and 6 contained ISAba1
      upstream of bla OXA-23 gene. Eighteen of these isolates carried the bla ADC-7
      gene, with 9 of the isolates having ISAba1 located upstream of this gene. This is
      the first report of the ISAba1/ADC-7 associated with OXAs genes in A. baumannii
      isolates from Colombia. 

PMID- 24031954
TI  - Regulation of T lymphocyte subpopulations in specific pathogen-free chickens
      following experimental fowl adenovirus-VIIIVIII infection.
AB  - Two-day-old specific pathogen-free (SPF) chickens were divided into two groups.
      Group I was inoculated orally with fowl adenovirus VIII (FAV-VIII). Group II
      served as a negative control. Chickens were investigated at various days post
      inoculation (dpi) by flow cytometric analysis for changes in T lymphocyte
      subpopulations in immune system and blood. In the thymus, CD3(+)T lymphocytes
      were increased at 25 dpi, with significant increases in the FAV infected noted at
      1, 12, 20dpi (p<0.05). This was accompanied by a corresponding increase of CD4(+)
      and CD8(+) T lymphocytes. In the spleen, CD3(+) and CD4(+) T lymphocytes were
      increased significantly at 30 dpi (p<0.01) whereas CD8(+) and TCR gamma delta(+)
      T lymphocytes were decreased at 1 (p<0.05), 30 dpi (p<0.01). An increase of
      CD3(+), CD4(+) and CD8(+) T lymphocytes was noticed in peripheral blood, and
      accompanied by a decrease of TCR gamma delta(+) T lymphocytes. These results
      demonstrated that infection with FAV-VIII causes significant fluctuations in T
      lymphocyte subpopulations in thymus, blood and spleen. It can be concluded that
      an infection with FAV-VIII has profound effects on the immune system, especially
      on cell mediated immune competency. 

PMID- 24031955
TI  - validated microbiological and HPLC methods for the determination of moxifloxacin
      in pharmaceutical preparations and human plasma.
AB  - The article presents a comparison between microbiological and high performance
      liquid chromatographic (HPLC) assays for quantification of moxifloxacin in
      tablets, ophthalmic solutions and human plasma. The microbiological method
      employed a cylinder-plate agar diffusion assay using a strain of Esherichia coli
      ATCC 25922 as the test organism and phosphate buffer (pH8) as the diluent. The
      calibration curves were linear (R(2) > 0.98) over a concentration range of 0.125
      to 16 ugml(-1). The within day and between days precisions were <= 4.47% and <=
      6.39% respectively. Recovery values were between 89.4 and 110.2%. The HPLC assay
      used Hypersil((r)) BDS C18 reversed phase column (250*4.6 mm, 5um) with a mobile
      phase comprising 20 mM ammonium dihydrogen orthophosphate (pH3) and acetonitrile
      (75:25) and flowing at 1.5 ml/min. The detection was at 295nm. The calibration
      curves were linear (R(2) > 0.999) over the range of 0.125 to 16 ug ml(-1). The
      within day and between days precisions were <= 4.07% and <= 5.09% respectively.
      Recovery values were between 97.7 and 107.6%. Similar potencies were obtained
      after the analysis of moxifloxacin tablets and ophthalmic solutions by both
      methods. Also pharmacokinetic parameters were calculated after the analysis of
      plasma samples of six male healthhy volunteers by both validated methods. 

PMID- 24031956
TI  - Antimicrobial activity of some medicinal plants from the cerrado of the
      centralwestern region of Brazil.
AB  - Ethanol extracts from six selected species from the Cerrado of the Central
      Western region of Brazil, which are used in traditional medicine for the
      treatment of infectious diseases and other medical conditions, namely
      Erythroxylum suberosum St. Hil. (Erythroxylaceae), Hyptis crenata Pohl. ex Benth.
      (Lamiaceae), Roupala brasiliensis Klotz. (Proteaceae), Simarouba versicolor St.
      Hil. (Simaroubaceae), Guazuma ulmifolia Lam. (Sterculiaceae) and Protium
      heptaphyllum (Aubl.) March. (Burseraceae), as well as fractions resulting from
      partition of these crude extracts, were screened in vitro for their antifungal
      and antibacterial properties. The antimicrobial activities were assessed by the
      broth microdilution assay against six control fungal strains, Candida albicans,
      C. glabrata, C. krusei, C. parapsilosis, C. tropicalis and Cryptococcus
      neoformans, and five control Gram-positive and negative bacterial strains,
      Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas
      aeruginosa and Staphylococcus aureus. Toxicity of the extracts and fractions
      against Artemia salina was also evaluated in this work. All plants investigated
      showed antimicrobial properties against at least one microorganism and two
      species were also significantly toxic to brine shrimp larvae. The results tend to
      support the traditional use of these plants for the treatment of respiratory and
      gastrointestinal disorders and/or skin diseases, opening the possibility of
      finding new antimicrobial agents from these natural sources. Among the species
      investigated, Hyptis crenata, Erythroxylum suberosum and Roupala brasiliensis
      were considered the most promising candidates for developing of future
      bioactivity-guided phytochemical investigations. 

PMID- 24031957
TI  - Mutations in the quinolone resistance-determining regions of gyrA and parC in
      Enterobacteriaceae isolates from Brazil.
AB  - Mutations in the quinolone resistance-determining regions (QRDR) in chromosomal
      gyrA and parC genes and fluoroquinolone susceptibility profiles were investigated
      in quinolone-resistant Enterobacteriaceae isolated from community and
      hospitalized patients in the Brazilian Southeast region. A total of 112 nalidixic
      acid-resistant enterobacterial isolates collected from 2000 to 2005 were
      investigated for mutations in the topoisomerases genes gyrA and parC by
      amplifying and sequencing the QRDR regions. Susceptibility to fluoroquinolones
      was tested by the agar dilution method. Amongst the 112 enterobacterial isolates,
      81 (72.3%) were resistant to ciprofloxacin and 5 (4.5%) showed reduced
      susceptibility. Twenty-six (23.2%) were susceptible to ciprofloxacin. Several
      alterations were detected in gyrA and parC genes. Escherichia coli isolates
      (47.7%) showed double mutations in the gyrA gene and a single one in the parC
      gene. Two unusual aminoacid substitutions are reported, an Asp87-Asn in a
      Citrobacter freundii isolate with reduced susceptibility to fluoroquinolones and
      a Glu84-Ala in one E. coli isolate. Only a parC gene mutation was found in
      fluoroquinolone-susceptible Enterobacter aerogenes. None of the isolates
      susceptible to ciprofloxacin presented mutations in topoisomerase genes. This
      comprehensive analysis of QRDRs in gyrA and parC genes, covering commonly
      isolated Enterobacteriaceae in Brazil is the largest reported up to now. 

PMID- 24031958
TI  - "In vitro" antifungal activity of ozonized sunflower oil on yeasts from
      onychomycosis.
AB  - The "in vitro" antifungal activity of ozonized sunflower oil (Bioperoxoil(r)) was
      tested on 101 samples of yeasts originating from onychomycosis using the disk
      diffusion method. The oil was efficacious against several clinical fungal
      strains: Candida parapsilosis, Candida albicans, Trichosporon asahii, Candida
      tropicalis and Candida guilliermondii. 

PMID- 24031959
TI  - A DNA pooling based system to detect Escherichia coli virulence factors in fecal
      and wastewater samples.
AB  - The availability of a useful tool for simple and timely detection of the most
      important virulent varieties of Escherichia coli is indispensable. To this end,
      bacterial DNA pools which had previously been categorized were obtained from
      isolated colonies as well as selected in terms of utilized phenotype; the pools
      were assessed by two PCR Multiplex for the detection of virulent E. coli eaeA,
      bfpA, stx1, stx2, ipaH, ST, LT, and aatA genes, with the 16S gene used as DNA
      control. The system was validated with 66 fecal samples and 44 wastewater
      samples. At least one positive isolate was detected by a virulent gene among the
      20 that were screened. The analysis of fecal samples from children younger than 6
      years of age detected frequencies of 25% LT positive strains, 8.3% eae, 8.3%
      bfpA, 16.7% ipaH, as well as 12.5 % aatA and ST. On the other hand, wastewater
      samples revealed frequencies of 25.7% eaeA positive, 30.3% stx1, 15.1% LT and
      19.7% aatA. This study is an initial step toward carrying out epidemiological
      field research that will reveal the presence of these bacterial varieties. 

PMID- 24031960
TI  - Bacteriological features of infectious spondylodiscitis at Mohammed V Military
      Teaching Hospital of Rabat.
AB  - To review the bacteriological features of infectious spondylodiscitis and provide
      recommendations for the initial therapy which remains empirical in our context.
      Retrospective study including patients diagnosed with spondylodiscitis over a
      period of 4 years (2006-2009) at the Rabat Military Teaching Hospital. During the
      study period, we analysed 30 cases: the mean age was 49.9 years and 21 cases
      (70%) were male. The patients were predominantly hospitalized in neurosurgery
      department (15/30) followed by rheumatology department (10/30). The site of
      infection was lumbar in 21 cases (21/30), dorsal in 7 cases (7/30). 26 cultures
      were positive of which 19 (19/26) were monomicrobial. Tuberculosis (TB) was
      implicated in 10 cases (10/30) including 4 cases in association with common
      organisms (Propionibacterium acnes, Staphylococcus aureus, Staphylococcus
      epidermidis, Corynebacterium species). Brucella melitensis was isolated in 1
      case. Infections caused by pyogenic bacteria were isolated in 15 cases of which
      12 (12/15) revealed simple organisms including Gram-positive cocci in 9 cases
      (9/12) with 3 cases of S. aureus and Gram-negative bacilli in 3 cases (3/12) with
      2 cases of P. aeruginosa. Blood cultures carried out for 16 patients were
      positive in 7 cases. The anatomopathologic exams carried out for 20 patients
      found in 6 cases epithelioid granulomata and giants cells with caseous necrosis
      in total concordance with TB culture. TB is the most frequent cause of
      spondylodiscitis in Morocco. Our study found the same frequency for non-specific
      and specific germs. Empirical treatment must take into account S. aureus and M.
      tuberculosis. 

PMID- 24031961
TI  - Prevalence of genotypes in Helicobacter pyloriisolates from patients in eastern
      Turkey and the association of these genotypes with clinical outcome.
AB  - There is not much information available regarding the prevalence of the genotypes
      of Helicobacter pylori isolates in Turkey, particularly in eastern Turkey. The
      aims of this study were to detect the prevalence of different genotypes of H.
      pylori in Turkish patients with gastrointestinal complaints and to determine the
      relationship of these genotypes with clinical outcome and sex. One hundred forty
      H. pylori isolates were examined for the presence of its genotypes by the PCR. We
      found that the prevalence of vacAs1,vacAs2, cagA, cagE, iceA1, iceA2 and babA2
      genes were 88.6%, 11.4%, 71.4%, 35.7%, 41.4%, 58.6%, and 62.1%, respectively. The
      most predominant vacA subtype was s1a (81.4%). The most vacA allelic combination
      detected were vacAs1m1 (65.2%) and s1m2 (53.9%) in patients with peptic ulcer and
      gastritis, respectively. The only vacAs1 isolate was significantly associated
      with gastritis and peptic ulcer (p<0.05). The vacAs1a, ml, slml and babA2 genes
      were significantly associated with peptic ulcer (p<0.05), whereas m2 gene was
      significantly associated with only gastritis (p<0.05). The difference between sex
      and genotypes was statistically significant among the cagA,vacAs1, iceA2 and
      babA2 genes. This study reported for the first time the prevalence of H. pylori
      genotypes in patients with gastrointestinal complaints in eastern Turkey. Further
      studies are needed to understand epidemiological importance of the genotypes of
      H. pylori isolates in this region and the association between the virulence genes
      and clinical outcome in different regions. 

PMID- 24031962
TI  - Production of peptide antibiotics by Bacillus sp. GU 057 indigenously isolated
      from saline soil.
AB  - A total of 112 soil samples were taken from differents areas of district D.I.Khan
      and Kohat (KPK) Pakistan and screened for production of antibiotics against the
      Micrococcus luteus and Staphylococcus aureus. Widest zone of inhibition (18mm)
      was produced by microorganism isolated from saline soil. The strain was later
      identified as Bacillus GU057 by standard biochemical assays. Maximum activity
      (18mm inhibition zone) was observed against Staphylococcus aureus after 48 hours
      of incubation at pH 8 and 4% concentration of glucose. The antibiotic was
      identified by autobiography as bacitracin. The Bacillus strain GU057 was
      confirmed as good peptide antibiotic producer and can effectively be indulged as
      biocontrol agent. 

PMID- 24031963
TI  - Inhibitory effect of essential oils against Trichosporon ovoides causing Piedra
      Hair Infection.
AB  - Piedra, is an asymptomatic fungal infection of the hair shaft, resulting in the
      formation of nodules of different hardness on the infected hair. The infection
      also known as Trichomycosis nodularis is a superficial fungal infection arising
      from the pathogen being restricted to the stratum corneum with little or no
      tissue reaction. The nodules are a concretion of hyphae and fruiting bodies of
      the fungus. Two varieties of Piedra may be seen, Black Piedra and White Piedra.
      The fungus Trichosporon ovoides is involved in the occurrence of both types of
      Piedras. The purpose of this study was to examine the effectiveness of selected
      essential oils for the control of growth of the fungus and to determine whether
      the antifungal effect was due to the major compounds of the oils. Two screening
      methods viz. Agar well diffusion assay and Minimum Inhibitory Concentration were
      adopted for the study. MIC and MFC were determined by tube dilution method.
      Essential oils from Eucalyptus, Ocimum basilicum, Mentha piperita, Cymbopogon
      flexuosus, Cymbopogon winterians, Trachyspermum ammi, Zingiber officinalis,
      Citrus limon, Cinnamomon zeylanicum, Salvia sclarea, Citrus aurantifolia,
      Melaleuca alternifolia, Citrus aurantium, Citrus bergamia, Pogostemon pathchouli,
      Cedrus atlantica, Jasminum officinale, Juniperus communis, Abelmoschus moschatus,
      Cyperus scariosus, Palargonium graveolens, Boswellia carterii, Rosa damascene,
      Veteveria zizanoides and Commiphora myrrha were evaluated. The essential oils of
      Cymbopogon winterians, Mentha piperita, Cinnamomum zeylanicum, Melaleuca
      alternifolia and Eucalyptus globulus were proved to be most effective against the
      fungus Trichosporon ovoides. 

PMID- 24031964
TI  - Efficacy of aqueous garlic extract on growth, aflatoxin B1 production, and cyto
      morphological aberrations of Aspergillus flavus, causing human ophthalmic
      infection: topical treatment of A. flavus keratitis.
AB  - By using agar well diffusion assay, antifungal activity of aqueous extract
      prepared from Egyptian garlic (Allium sativum L.) was evaluated in vitro against
      two strains of Aspergillus flavus (OC1 and OC10) causing human ocular infection.
      The recorded minimum inhibitory concentration (MIC) for growth inhibition of both
      strains was 3.60 mg/ml. Aqueous garlic extract (AGE) was used in successive in
      vivo tests as an attempt to cure rabbit's fungal keratitis caused by A. flavus
      OC1. Findings showed that diluted preparation of AGE was effective topical
      antifungal agent and succeeded to cure severe A. flavus keratitis in a time
      course less than 10 days without any observable side effects. Microscopic
      examination showed that AGE induced deleterious cyto-morphological aberrations in
      A. flavus target cells. AGE applied to Czapek's broth via contact method was more
      effective on growth, spores and aflatoxin B1 production than AGE applied to the
      same broth at the same concentration via fumigation method. 

PMID- 24031965
TI  - Effect of combined function of temperature and water activity on the growth of
      Vibrio harveyi.
AB  - Vibrio harveyi is considered as a causative agent of the systemic disease,
      vibriosis, which occurs in many biological fields. The effects of temperatures
      (12.9-27.1  degrees C) and water activity (NaCl% 0.6%-3.4%) on V. harveyi were
      investigated. The behavior and growth characteristics of V. harveyi was studied
      and modeled. Growth curves were fitted by using Gompertz and Baranyi models, and
      the Baranyi model showed a better fittness. Then, the maximum growth rates
      (MUmax) and lag phase durations (LPD, lambda) obtained from both Gompertz and
      Baranyi model were modeled as a combination function of temperature and water
      activity using the response surface and Arrhenius-Davey models for secondary
      model. The value of r(2), MSE, bias and accuracy factor suggest Baranyi model has
      better fitness than Gompertz model. Furthermore, validation of the developed
      models with independent data from ComBase also shown better interrelationship
      between observed and predicted growth parameter when using Baranyi model. 

PMID- 24031966
TI  - In vitro antagonistic growth effects of Lactobacillus fermentum and lactobacillus
      salivarius and their fermentative broth on periodontal pathogens.
AB  - As lactobacilli possess an antagonistic growth property, these bacteria may be
      beneficial as bioprotective agents for infection control. However, whether the
      antagonistic growth effects are attributed to the lactobacilli themselves or
      their fermentative broth remains unclear. The antagonistic growth effects of
      Lactobacillus salivarius and Lactobacillus fermentum as well as their
      fermentative broth were thus tested using both disc agar diffusion test and broth
      dilution method, and their effects on periodontal pathogens, including
      Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalis in
      vitro at different concentrations and for different time periods were also
      compared. Both Lactobacillus salivarius and Lactobacillus fermentum and their
      concentrated fermentative broth were shown to inhibit significantly the growth of
      Streptococcus mutans, Streptococcus sanguis, and Porphyromonas gingivalis,
      although different inhibitory effects were observed for different pathogens. The
      higher the counts of lactobacilli and the higher the folds of concentrated
      fermentative broth, the stronger the inhibitory effects are observed. The
      inhibitory effect is demonstrated to be dose-dependent. Moreover, for the
      lactobacilli themselves, Lactobacillus fermentum showed stronger inhibitory
      effects than Lactobacillus salivarius. However, the fermentative broth of
      Lactobacillus fermentum showed weaker inhibitory effects than that of
      Lactobacillus salivarius. These data suggested that lactobacilli and their
      fermentative broth exhibit antagonistic growth activity, and consumption of
      probiotics or their broth containing lactobacilli may benefit oral health. 

PMID- 24031967
TI  - Refrigerated poultry breast fillets packed in modified atmosphere and irradiated:
      bacteriological evaluation, shelf life and sensory acceptance.
AB  - In the present study the effects on shelf life and sensory acceptance of gamma
      irradiated refrigerated poultry breast fillets subjected to modified atmosphere
      packaging (80% CO2/20% N2 or vacuum) were investigated. After irradiation with 2
      kGy, sensory acceptance tests and monitoring of bacterial growth were performed
      in order to determine the sanitary quality of the samples. It has been found that
      irradiation, used in combination with modified atmosphere packaging, can double
      the shelf life of refrigerated poultry breast fillets by reducing the populations
      of aerobic mesophilic and psychrotrophic bacteria, enterobacteria, coliforms,
      Listeria spp. and Aeromonas spp., without significantly modifying its color or
      its overall appearance, the lactic acid bacteria being the most resistant to
      exposure to radiation and carbon dioxide. 

PMID- 24031968
TI  - Microbiological quality of salmon (Salmo salar) sold in cities of the state of
      SaO Paulo, Brazil.
AB  - The present paper evaluated the microbiology of salmon by quantifying mesophilic
      heterotrophic microorganisms, total and thermotolerant coliforms, and the
      presence of Vibrio parahaemolyticus, Staphylococcus aureus, Salmonella sp.,
      Escherichia coli and Aeromonas sp. in the meat. This study can provide technical
      support for the suggestion of a new regulation of a Brazilian legislation through
      specific microbiological standards concerning the consumption of raw fish. A
      number of 31 (16 cooled and 15 frozen) samples of salmon were collected in the
      retail market network of a few cities in the State of Sao Paulo, Brazil. Results
      presented populations of mesophilic heterotrophic microorganisms ranging from 1.0
      * 10 and 3.9 * 10(6) CFU/g, total and thermotolerant coliforms in 32.25% and
      19.35% of the samples, respectively, and Aeromonas sp. in 41.95% of the samples
      with a populational variation ranging from 2.0 * 10(2) to 8.0 * 10(3) CFU/g.
      Staphylococcus aureus was found in one sample whereas Vibrio parahaemolyticus,
      Salmonella sp. and Escherichia coli were not found. These results demonstrated
      the presence of potencially pathogenic microorganisms in fresh fish consumed in
      Brazil, highlighting the necessity of control measures to avoid public health
      problems related to the consumption of raw fish. 

PMID- 24031969
TI  - Growth of enterotoxin producing Bacillus cereus in meat substrate at 10oC and
      30oC.
AB  - The behaviour of enterotoxin-producing Bacillus cereus in meat was investigated
      by inoculating spore suspensions of five cultures into meat substrate (pH 5.8)
      and incubating at 10oC and 30oC. The bacterial populations were evaluated after
      different times by plate counts in nutrient agar. All the cultures presented
      growth at 30oC with the generation time varying from 28.8 to 36.0 minutes. Three
      cultures also presented growth at 10oC with generation times between 10.16 and
      28.38 h. Considering the results, it was concluded that meat kept at abusive
      temperatures would be subject to development of this microorganism. 

PMID- 24031970
TI  - Survival of Escherichia coli o157:h7 co-cultured with different levels of
      pseudomonas fluorescens and lactobacillus plantarum on fresh beef.
AB  - The purpose of this study was to investigate the effect of different levels of
      Pseudomonas fluorescens (10(2) and 10(6) log10 cfu/ml) and Lactobacillus
      plantarum (10(2) and 10(4) log10 cfu/ml) on the growth of Escherichia coli
      O157:H7 on beef loins. Beef loins inoculated with E. coli O157:H7 and P.
      fluorescens were aerobically stored for 7 days at 4 oC, while those inoculated
      with E. coli O157:H7 and L. plantarum were vacuum packaged and stored for 8 weeks
      at 4 oC. Aerobic Plate Counts (APC), E. coli O157:H7 and either P. fluorescens or
      L. plantarum counts were determined at different storage intervals. For the
      aerobically packaged beef loins, E. coli O157:H7 was detected throughout the 7
      day storage period regardless of the P. fluorescens level in the inoculum. For
      the vacuum packaged beef loins, similar inoculum levels of E. coli O157:H7 and L.
      plantarum allowed E. coli O157:H7 to survive until week 5 of storage, while a
      higher inoculum level of L. plantarum inhibited E. coli O157:H7 from week 3. Once
      fresh beef has been contaminated with E. coli O157:H7, the level of P.
      fluorescens in the background flora does not inhibit its survival and growth.
      However, under vacuum storage, the application of L. plantarum as a
      biopreservative inhibits the survival of E. coli O157:H7 on beef. The higher the
      level of L. plantarum in the system, the earlier the onset of the inhibition.
      Farmers and abattoirs have to strengthen preventive strategies to eliminate
      contamination of beef carcasses with E. coli O157:H7. 

PMID- 24031971
TI  - Inhibition of Listeria monocytogenes in minas frescal cheese by free and
      nanovesicle-encapsulated nisin.
AB  - The effectiveness of free and nanovesicle-encapsulated nisin to control Listeria
      monocytogenes in Minas Frescal cheese was investigated. Commercial nisin was
      encapsulated into liposomes of partially purified soy lecithin. Free (0.1 mg/mL
      and 0.25 mg/mL) and nanovesicle-encapsulated nisin (0.25 mg/mL) were applied onto
      the surface of cheese samples, and L. monocytogenes was inoculated before
      incubation at 6-8 degrees C for 28 days. A bactericidal effect was observed with
      0.25 mg/mL free nisin; a bacteriostatic effect was observed for liposome
      encapsulated nisin and 0.1 mg/mL free nisin. Free nisin was more efficient than
      nisin-loaded liposomes in controlling L. monocytogenes. Possible reasons for this
      behavior, and also the significance of nisin to soft cheeses are discussed. Nisin
      acted as a suitable barrier within hurdle technology, potentially extending the
      shelf-life and safety of fresh cheeses. 

PMID- 24031972
TI  - Microbiological quality and other characteristics of refrigerated chicken meat in
      contact with cellulose acetate-based film incorporated with rosemary essential
      oil.
AB  - Antimicrobial active packaging delays or inhibits microorganism growth in packed
      products, and it can be used in a variety of food systems. The objective of the
      present research was to develop packaging incorporated with natural antimicrobial
      agents (active film). The effects of the active film on the spoilage, pathogenic
      microorganism counts, pH and color of the refrigerated chicken breast cuts were
      analyzed. Cellulose acetate-based active films incorporating two concentrations
      (20% and 50%, v/w) of rosemary (Rosmarinus officinalis L.) essential oil were
      manufactured and placed in contact with the chicken breast cuts for six days. An
      analysis of variance and mean comparison tests (Tukey's test, p<0.05) were
      performed on the results. The films that contained 20% essential oil and were
      intercalated with chicken breast samples did not demonstrate significant effects
      on the control of psychrotrophic or total coliform microorganisms during the
      storage period; however, the films incorporated with 50% essential oil
      demonstrated efficacy toward the control of coliforms during the storage of the
      samples (6 days, 2 +/- 2oC). The pH was related to the psychrotrophic
      microorganism count and was not influenced by the treatment. The color was not
      influenced by the time of storage or the treatment. The results demonstrate that
      active films incorporating 50% rosemary essential oil are effective at
      controlling certain microorganisms in chicken breast cuts. 

PMID- 24031973
TI  - Occurrence of aflatoxin B1 in natural products.
AB  - The media claims for the consumption of natural resource-based food have
      gradually increased in both developing and developed countries. The interest in
      the safety of these products is partially due to the possible presence of
      toxigenic fungi acting as mycotoxin producers, such as aflatoxins produced during
      the secondary metabolism of Aspergillus flavus, A. parasiticus and A. nomius.
      Aflatoxins, mainly aflatoxin B1, are directly associated with liver cancer in
      human beings. This paper is aimed at evaluating the presence of aflatoxin B1 in a
      few vegetable drugs, dried plant extracts and industrialized products traded in
      2010 in the city of Belo Horizonte, State of Minas Gerais, Brazil. The method
      used for the quantification of aflatoxin B1 was based on extraction through
      acetone:water (85:15), immunoaffinity column purification followed by separation
      and detection in high efficiency liquid chromatography. Under the conditions of
      analysis, the Limits of Detection and Quantification were 0.6 ug kg(-1) and 1.0
      ug kg(-1) respectively. The complete sets of analyses were carried out in
      duplicate. Aflatoxin B1 was noticed in a single sample (< 1.0 ug kg(-1)). The
      results revealed low aflatoxin B1 contamination in the products under analysis.
      However, it is required to establish a broad monitoring program in order to
      obtain additional data and check up on the actual extension of contamination. 

PMID- 24031974
TI  - Detection of airborne psychrotrophic bacteria and fungi in food storage
      refrigerators.
AB  - The purpose of this study was to determine the microbiological air quality
      (psychrotrophic bacteria and airborne fungi) and distribution of fungi in
      different types of ready-to-eat (RTE) food-storage refrigerators (n=48) at
      selected retail stores in the city of Edirne, Turkey. Refrigerators were
      categorized according to the type of RTE food-storage: meat products, vegetables,
      desserts, or a mix of food types. Microbiological quality of air samples was
      evaluated by using a Mas-100 Eco Air Sampler. Four refrigerators (all containing
      meat products, 8.3%) produced air samples with undetectable microorganisms. The
      highest detected mean value of airborne psychrotrophic bacteria and fungi was
      82.3 CFU/m(3) and 54.6 CFU/m(3), respectively and were found in mixed-food
      refrigerators. The dominant airborne fungal genera found were Penicillium
      (29.0%), Aspergillus (12.0%), Mucor (9%), Cladosporium (8%), Botyrtis (7%), and
      Acremonium (6%). By definition, RTE food does not undergo a final treatment to
      ensure its safety prior to consumption. Therefore, ensuring a clean storage
      environment for these foods is important to prevent food-borne disease and other
      health risks. 

PMID- 24031975
TI  - Mycoflora study in a wheat flour mill of Argentina.
AB  - THE MYCOFLORA OF THE ENVIRONMENT: wheat conditioning, milling and screening, and
      filling zone, as well as, raw material -wheat-, intermediate product -grits- and
      end product -flour- on day 1, and after cleaning improvements -days 45 and 90-
      were studied in an Argentine wheat mill. Samples were incubated at 28 degrees C
      for 5-7 days on Malt Extract Agar with chloramphenicol (100 mg L(-1)) and the
      results were expressed in colony forming units per cubic meter of air (CFU m(-3))
      or per gram of sample (CFU g(-1)), respectively. Fungal genera and species were
      isolated and identified and the potential toxicogenic capacity of the Aspergillus
      flavus and Fusarium graminearum isolated was studied. Time-Place and Time-Product
      multifactorial ANOVA were carried out. After cleaning improvements, CFU m(-3) of
      air decreased as a function of time. Cladosporium and Alternaria were abundant in
      every zone, Aspergillus predominated in the wheat conditioning zone and
      Penicillium and Eurotium decreased with time. Wheat was more contaminated than
      grits and flour; Aspergillus, Eurotium and Mucoraceae family were the most
      abundant. Deoxynivalenol was above the levels allowed in wheat, being acceptable
      in grits and flour. Aflatoxin and Zearalenone showed acceptable levels. When
      studied in vitro, 53% of Aspergillus flavus and 100% of Fusarium graminearum
      isolates, produced Total Aflatoxins, and Deoxynivalenol and Zearalenone,
      respectively.

PMID- 24031976
TI  - An evaluation and partial characterization of a bacteriocin produced by
      Lactococcus lactis subsp lactis ST1 isolated from goat milk.
AB  - A bacteriocin-like inhibitory substance producing Lactococcus lactis subsp lactis
      strain, ST1, isolated from goat milk of Iranian origin and with broad spectrum of
      activity and desirable technical properties was used for evaluating some futures
      of bacteriocin inhibitory activity. Cell growth and bacteriocin production
      studies were carried out in MRS medium incubated statically under uncontrolled pH
      condition. The antibacterial activity presented a primary metabolite pattern and
      showed a rapid decrease at the stationary phase. Microaerobiosis and capnophily
      growth conditions resulted in higher bacteriocin production while aerobiosis
      showed negative effect on both cell growth and bacteriocin production.
      Bacteriocin production, on the other hand, was favored in MRS broth (pH; 6.5)
      inoculated with 0.1 ml l(-1) fresh culture when incubation was carried out at 30 
      degrees C. This indicated that the conditions resulted in higher levels of growth
      were frequently favoring bacteriocin production by ST1 as well. Decrease in
      activity, at the stationary growth phase, was much pronounced in favored growth
      condition. Nutrient depletion, deferent effect of low pH on bacteriocin
      production and/or protein degradation seemed more responsible for this
      phenomenon. The study also provided further data on new method for bacteriocin
      release from the cell wall of producer. It was clearly shown that both heating
      and ultrasound shock for 5 min at pH 2 could increase bacteriocin activity
      significantly. The release was more pronounced in the presence of 0.5% Tween80. 

PMID- 24031977
TI  - Occurrence of Salmonella sp. and coagulase-positive staphylococci in raw eggs and
      Coalho cheese: comparative study between two cities of Brazil's northeast.
AB  - Microbiological analyses of chicken eggs in Recife and Salvador have shown a high
      occurrence of Salmonella in the egg shells and yolks. Likewise, the occurrence of
      Salmonella plus coagulase-positive staphylococci in Coalho cheese reached
      alarming levels. The data revealed a significant risk of infections and
      intoxications from consuming these foods in the cities. 

PMID- 24031978
TI  - Characteristics of a beta-1,4-D endoglucanase from Trichoderma virens wholly
      applied in a palm-fruit husk-based diet for poultry layers.
AB  - The characteristics of an endoglucanase produced by a Trichoderma virens strain
      T9 newly isolated from a palm-fruit husk dump site, its physiological
      characteristics and enzyme production were studied. Whole cells of the
      depolymerizing-enzyme producing T. virens were applied to palm-fruit husk and
      bird performance characteristics when employed as poultry diet additive were
      considered. Endoglucanase activity in submerged fermentation was 1.6 nkat.
      Optimum activity was recorded at pH 6.0 and 55 degrees C. The enzyme retained 50%
      residual glucanase activity at 70 degrees C for 10 minutes. 1.0% Tween-80 and SDS
      yielded endoglucanase activity 2.15 times higher than the control. Activity was
      boosted by 20mM Ca(2+) (115.0%); 10mM K(+) (106.5%); and was totally inhibited by
      1mM Hg(2+). The addition of T. virens-fermented palm-fruit husk with other layer
      feed components on the bird characteristics showed that change in bird weight
      between the control and test birds were not significantly different (p>0.05) but
      differed in terms of daily feed ingested (p<0.05). The feed to weight-gain ratio
      was best with the unmodified palm-fruit husk based diet (8.59). There was no
      significant difference in the egg weights from modified palm-fruit husk based
      diet and control (p>0.05). The shell thickness (0.64mm) and yolk content (23.61%)
      were highest in the microbially-modified husk diet. The alternative to maize
      based diets proffered by the application of T. virens-modified palm-fruit husk in
      poultry nutrition in terms of bird weight and feed to weight-gain ratio affords
      the poultry farmer an economic advantage and allows for a greater utilization of
      the maize in human diets. 

PMID- 24031979
TI  - Effect of precursors feeding and media manipulation on production of novel
      anticancer pro-drug camptothecin from endophytic fungus.
AB  - We have established methodology for the isolation and characterization of a novel
      endophytic fungus from the inner bark of medicinal plant Nothapodytes foetida,
      which produced camptothecin in Sabouraud broth (SB) under shake flask conditions.
      Camptothecin and its related compounds are at present obtained by extraction from
      intact plants, but fungal endopytes may be an alternative source of production.
      In present study we have observed the effect of different nutrient combinations
      and precursors (tryptophan, tryptamine, geraniol, citral, mevalonic acid and
      leucine) on the accumulation of camptothecin by endophytic fungus Entrophospora
      infrequens. The precursors were fed either alone or in combinations (tryptophan
      and geraniol, tryptophan and citral, tryptophan and mevalonic acid, tryptophan
      and leucine). The highest camptothecin content was observed in the range of 503
      +/- 25ug/100g dry cell mass in Sabouraud medium. Camptothecin content in the
      medium was increased by 2.5 folds by the presence of tryptophan and leucine
      whereas the production with trytophan was also significantly different from other
      treatments. Furthermore, the effect of fungal camptothecin on the morphology of
      human cancer cell lines was also studied. The treated cells showed reduction in
      size, condensation of nucleus and the protoplasmic extensions were reduced. All
      these characteristics are found in apoptotic cells. 

PMID- 24031980
TI  - 'Synthetic lipase' production from a newly isolated Sporidiobolus pararoseus
      strain by submerged fermentation.
AB  - The lipase produced by a newly isolate Sporidiobolus pararoseus strain has
      potential catalysis ability for esterification reactions. In order to improve its
      synthetic activity, this work aimed at optimizing 'synthetic lipase' production
      by submerged fermentation of a conventional media based on peptone, yeast
      extract, NaCl and olive oil using experimental design technique. According to the
      results obtained in the first experimental design (2(4-1)), yeast extract and
      NaCl concentrations were tested to further optimization by response surface
      methodology. The maximum 'synthetic lipase' activity obtained was 26.9 U/mL in
      the optimized media (5.0, 6.8, 7.0 and 1.0% (wt/v) of peptone, yeast extract,
      NaCl and olive oil, respectively), representing a 6.36-fold increase compared to
      the initial medium. The time course of 'synthetic lipase' production in the
      optimized condition was evaluated in terms of synthetic activity, protease
      activity, biomass and total carbon and the maximum synthetic activity was
      observed during the stationary phase of growth. 

PMID- 24031981
TI  - Ethanol fermentation of sugarcane molasses by Zymomonas mobilis MTCC 92
      immobilized in Luffa cylindrica L. sponge discs and Ca-alginate matrices.
AB  - Bio-ethanol production from cane molasses (diluted to 15 % sugar w/v) was studied
      using the bacterium, Zymomonas mobilis MTCC 92 entrapped in luffa (Luffa
      cylindrica L.) sponge discs and Ca-alginate gel beads as the immobilizing
      matrices. At the end of 96 h fermentation, the final ethanol concentrations were
      58.7 +/- 0.09 and 59.1 +/- 0.08 g/l molasses with luffa and Ca-alginate entrapped
      Z. mobilis cells, respectively exhibiting 83.25 +/- 0.03 and 84.6 +/- 0.02 %
      sugar conversion. There was no statistical significant difference (Fischer's LSD)
      in sugar utilization (t = 0.254, p<0.801) and ethanol production (t =-0.663,
      p<0.513) between the two immobilization matrices used. Further, the immobilized
      cells in both the matrices were physiologically active for three more cycles of
      operation with less than 15 % decrease in ethanol yield in the 4(th) cycle, which
      was due to some leakage of cells. In conclusion, luffa sponge was found to be
      equally good as Ca-alginate as a carrier material for bacterial (Z. mobilis) cell
      immobilization for ethanol production. Further, it has added advantages such as
      it is cheap, non-corrosive and has no environmental hazard. 

PMID- 24031982
TI  - Lignocellulolytic enzyme production of Pleurotus ostreatus growth in
      agroindustrial wastes.
AB  - The mushroom Pleurotus ostreatus has nutritional and medicinal characteristics
      that depend on the growth substrate. In nature, this fungus grows on dead wood,
      but it can be artificially cultivated on agricultural wastes (coffee husks,
      eucalyptus sawdust, corncobs and sugar cane bagasse). The degradation of
      agricultural wastes involves some enzyme complexes made up of oxidative (laccase,
      manganese peroxidase and lignin peroxidase) and hydrolytic enzymes (cellulases,
      xylanases and tanases). Understanding how these enzymes work will help to improve
      the productivity of mushroom cultures and decrease the potential pollution that
      can be caused by inadequate discharge of the agroindustrial residues. The
      objective of this work was to assess the activity of the lignocellulolytic
      enzymes produced by two P. ostreatus strains (PLO 2 and PLO 6). These strains
      were used to inoculate samples of coffee husks, eucalyptus sawdust or eucalyptus
      bark add with or without 20 % rice bran. Every five days after substrate
      inoculation, the enzyme activity and soluble protein concentration were
      evaluated. The maximum activity of oxidative enzymes was observed at day 10 after
      inoculation, and the activity of the hydrolytic enzymes increased during the
      entire period of the experiment. The results show that substrate composition and
      colonization time influenced the activity of the lignocellulolytic enzymes. 

PMID- 24031983
TI  - Antimycobacterial activity of a Brevibacillus laterosporusstrain isolated from a
      moroccan soil.
AB  - The treatment of tuberculosis has become more difficult with the worldwide spread
      of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of
      Mycobacterium tuberculosis. Moreover, the prevalence of human disease caused by
      atypical mycobacteria has also increased in the past two decades and has further
      complicated the problem of the treatment of mycobacterial infections. It is
      therefore urgent to develop new highly active molecules against these bacteria.
      The present study reports the isolation from a Moroccan soil of a Bacillus strain
      that exhibits an important antimycobacterial activity. The strain was identified
      as Brevibacillus laterosporus using DNA sequencing of the 16S ribosomal RNA gene.
      The antimycobacterial activity was assigned to a substance with a protein nature.
      This nature was revealed using a liquid-liquid extraction with organic solvents,
      precipitation with ammonium sulfate and treatment with a protease. This study
      suggested the identification and the characterization of this active metabolite
      enabling therapeutic investigations further. 

PMID- 24031984
TI  - Effect of acid hydrolysis and fungal biotreatment on agro-industrial wastes for
      obtainment of free sugars for bioethanol production.
AB  - This study was designed to evaluate selected chemical and microbiological
      treatments for the conversion of certain local agro-industrial wastes (rice
      straw, corn stalks, sawdust, sugar beet waste and sugarcane bagasse) to ethanol.
      The chemical composition of these feedstocks was determined. Conversion of wastes
      to free sugars by acid hydrolysis varied from one treatment to another. In single
      stage dilute acid hydrolysis, increasing acid concentration from 1 % (v/v) to 5 %
      (v/v) decreased the conversion percentage of almost all treated agro-industrial
      wastes. Lower conversion percentages for some treatments were obtained when
      increasing the residence time from 90 to 120 min. The two-stage dilute acid
      hydrolysis by phosphoric acid (1.0 % v/v) followed by sulphuric acid (1.0 % v/v)
      resulted in the highest conversion percentage (41.3 % w/w) on treated sugar beet
      waste. This treatment when neutralized, amended with some nutrients and
      inoculated with baker's yeast, achieved the highest ethanol concentration (1.0 %
      v/v). Formation of furfural and hydroxymethylfurfural (HMF) were functions of
      type of acid hydrolysis, acid concentration, residence time and feedstock type.
      The highest bioconversion of 5 % wastes (37.8 % w/w) was recorded on sugar beet
      waste by Trichoderma viride EMCC 107. This treatment when followed by baker's
      yeast fermentation, 0.41 % (v/v) ethanol and 8.2 % (v/w) conversion coefficient
      were obtained. 

PMID- 24031985
TI  - Endoglucanase production with the newly isolated Myceliophtora sp. i-1d3b in a
      packed bed solid state fermentor.
AB  - This work is aimed to produce endoglucanase through solid state fermentation in a
      packed bed bioreactor with the use of the fungus Myceliophtora sp. I-1D3b using a
      mixture of wheat bran (WB) and sugar cane bagasse (SCB) as culture medium.
      Preliminary tests were performed in polypropylene plastic bags, controlling the
      variables temperature (40, 45, and 50 degrees C), initial moisture content (75,
      80, and 85%, w.b.), and weight proportion SCB/WB (1:1, 7:3, and 9:1). The highest
      enzyme activities in plastic bags were obtained using the substrate proportion of
      7:3, 50 degrees C temperature, and 80% initial moisture content (878 U/grams of
      dry solid). High activities of filter-paper cellulase and xylanase were also
      obtained in plastic bags and some results are reported. For the packed bed
      experiments, the temperature (45 and 50 degrees C) and the air flow rate (80, 100
      and 120L/h) were the controlled variables. Activity of endoglucanase was similar
      to plastic bag tests. A longitudinal gradient of moisture content, was observed
      increasing from the bottom to the top of the reactor, even though the
      longitudinal enzyme activity profile was flat for almost the whole bed. Air flow
      rate did not affect enzyme activity, while experiments carried out at 50 degrees
      C showed higher enzyme activities. The maximum temperature peak observed was at
      about 6 degrees C above the process temperature. 

PMID- 24031986
TI  - Utilization of Agro-industrial Wastes for the Simultaneous Production of Amylase
      and Xylanase by Thermophilic Actinomycetes.
AB  - Agro-industrial wastes such as sugarcane bagasse, wheat bran, rice bran, corn cob
      and wheat straw are cheapest and abundantly available natural carbon sources. The
      present study was aimed to production of amylase and xylanase simultaneously
      using agro-industrial waste as the sole carbon source. Seven thermophilic strains
      of actinomycete were isolated from the mushroom compost. Among of these, strain
      designated MSC702 having high potential to utilize agro-industrial wastes for the
      production of amylase and xylanase. Strain MSC702 was identified as novel species
      of Streptomyces through morphological characterization and 16S rRNA gene
      sequence. Enzyme production was determined using 1% (w/v) of various agro
      industrial waste in production medium containing (g/100mL): K2HPO4 (0.1),
      (NH4)2SO4 (0.1), NaCl (0.1), MgSO4 (0.1) at pH 7.0 after incubation of 48 h at 50
      degrees C. The amylase activity (373.89 IU/mL) and xylanase activity (30.15
      IU/mL) was maximum in rice bran. The decreasing order of amylase and xylanase
      activity in different type of agro-industrial wastes were found rice bran (RB) >
      corn cob (CC) > wheat bran (WB) > wheat straw (WS) > sugarcane bagasse (SB) and
      rice bran (RB) > wheat bran (WB) > wheat straw (WS) > sugarcane bagasse (SB) >
      corn cob (CC), respectively. Mixed effect of different agro-industrial wastes was
      examined in different ratios. Enzyme yield of amylase and xylanase was ~1.3 and
      ~2.0 fold higher with RB: WB in 1:2 ratio. 

PMID- 24031987
TI  - Optimization of flask culture medium and conditions for hyaluronic acid
      production by a Streptococcus equisimilis mutant nc2168.
AB  - A mutant designated NC2168, which was selected from wild-type Streptococcus
      equisimilis CVCC55116 by ultraviolet ray combined with(60)Co-gamma ray treatment
      and does not produce streptolysin, was employed to produce hyaluronic acid (HA).
      In order to increase the output of HA in a flask, the culture medium and
      conditions for NC2168 were optimized in this study. The influence of culture
      medium ingredients including carbon sources, nitrogen sources and metal ions on
      HA production was evaluated using factional factorial design. The mathematical
      model, which represented the effect of each medium component and their
      interaction on the yield of HA, was established by the quadratic rotary
      combination design and response surface method. The model estimated that, a
      maximal yield of HA could be obtained when the concentrations of yeast extract,
      peptone, glucose, and MgSO4 were set at 3 g/100 mL, 2 g/100 mL, 0.5 g/100 mL and
      0.15 g/100 mL, respectively. Compared with the values obtained by other runs in
      the experimental design, the optimized medium resulted in a remarkable increase
      in the output of HA and the maximum of the predicted HA production was 174.76
      mg/L. The model developed was accurate and reliable for predicting the production
      of HA by NC2168.Cultivation conditions were optimized by an orthogonal
      experimental design and the optimal conditions were as follows: temperature 33
      degrees C, pH 7.8, agitation speed 200 rpm, medium volume 20 mL. 

PMID- 24031989
TI  - Toxicological evaluation of vegetable oils and biodiesel in soil during the
      biodegradation process.
AB  - Vegetable oils and their derivatives, like biodiesel, are used extensively
      throughout the world, thus posing an environmental risk when disposed. Toxicity
      testing using test organisms shows how these residues affect ecosystems. Toxicity
      tests using earthworms (Eisenia foetida) are widespread because they are a
      practical resource for analyzing terrestrial organisms. For phytotoxicological
      analysis, we used seeds of arugula (Eruca sativa) and lettuce (Lactuca sativa) to
      analyze the germination of seeds in contaminated soil samples. The toxicological
      experiment was conducted with four different periods of biodegradation in soil:
      zero days, 60 days, 120 days and 180 days. The studied contaminants were soybean
      oil (new and used) and biodiesel (B100). An evaluation of the germination of both
      seeds showed an increased toxicity for all contaminants as the biodegradation
      occurred, biodiesel being the most toxic among the contaminants. On the other
      hand, for the tests using earthworms, the biodiesel was the only contaminant that
      proved to be toxic. Therefore, the higher toxicity of the sample containing these
      hydrocarbons over time can be attributed to the secondary compounds formed by
      microbial action. Thus, we conclude that the biodegradation in soil of the
      studied compounds requires longer periods for the sample toxicity to be decreased
      with the action of microorganisms. 

PMID- 24031988
TI  - Isolation and characterization of endophytic bacteria isolated from the leaves of
      the common bean (Phaseolus vulgaris).
AB  - The common bean is one of the most important legumes in the human diet, but
      little is known about the endophytic bacteria associated with the leaves of this
      plant. The objective of this study was to characterize the culturable endophytic
      bacteria of common bean (Phaseolus vulgaris) leaves from three different
      cultivars (Vermelhinho, Talisma, and Ouro Negro) grown under the same field
      conditions. The density of endophytic populations varied from 4.5 x 10(2) to 2.8
      x 10(3) CFU g(-1) of fresh weight. Of the 158 total isolates, 36.7% belonged to
      the Proteobacteria, 32.9% to Firmicutes, 29.7% to Actinobacteria, and 0.6% to
      Bacteroidetes. The three P. vulgaris cultivars showed class distribution
      differences among Actinobacteria, Alphaproteobacteria and Bacilli. Based on 16S
      rDNA sequences, 23 different genera were isolated comprising bacteria commonly
      associated with soil and plants. The genera Bacillus, Delftia, Methylobacterium,
      Microbacterium, Paenibacillus, Staphylococcus and Stenotrophomonas were isolated
      from all three cultivars. To access and compare the community structure,
      diversity indices were calculated. The isolates from the Talisma cultivar were
      less diverse than the isolates derived from the other two cultivars. The results
      of this work indicate that the cultivar of the plant may contribute to the
      structure of the endophytic community associated with the common bean. This is
      the first report of endophytic bacteria from the leaves of P. vulgaris cultivars.
      Future studies will determine the potential application of these isolates in
      biological control, growth promotion and enzyme production for biotechnology. 

PMID- 24031990
TI  - Water quality and diversity of yeasts from tropical lakes and rivers from the Rio
      Doce basin in Southeastern Brazil.
AB  - Yeast communities were assessed in 14 rivers and four lakes from the Doce River
      basin in Brazil, during the rainy and dry seasons of the years 2000 and 2001.
      Water samples were collected at the subsurface in all sites. The following
      physical and chemical parameters were measured: temperature, dissolved oxygen,
      pH, electrical conductivity, total phosphorus, ortho-phosphate, ammonium,
      nitrate, nitrite and total nitrogen and the counts of faecal coliforms and
      heterotrophic bacteria were carried out to characterize the aquatic environmental
      sampled. The yeast counts were higher in aquatic environments with the highest
      counts of coliform and heterotrophic bacteria. These environments receive a high
      influx of domestic and industrial waste. A total of 317 isolates identified in
      forty eight yeast species were recorded in the sites sampled and the specie
      Aureobasidium pullulans were found in eleven out of eighteen sites sampled and
      some opportunistic pathogens such as the yeast species Candida krusei were
      isolated only in the polluted rivers with a positive correlation with the biotic
      and abiotic parameters that indicate sewage contamination. 

PMID- 24031991
TI  - Screening and isolation of halophilic bacteria producing industrially important
      enzymes.
AB  - Halophiles are excellent sources of enzymes that are not only salt stable but
      also can withstand and carry out reactions efficiently under extreme conditions.
      The aim of the study was to isolate and study the diversity among halophilic
      bacteria producing enzymes of industrial value. Screening of halophiles from
      various saline habitats of India led to isolation of 108 halophilic bacteria
      producing industrially important hydrolases (amylases, lipases and proteases).
      Characterization of 21 potential isolates by morphological, biochemical and 16S
      rRNA gene analysis found them related to Marinobacter, Virgibacillus,
      Halobacillus, Geomicrobium, Chromohalobacter, Oceanobacillus, Bacillus, Halomonas
      and Staphylococcus genera. They belonged to moderately halophilic group of
      bacteria exhibiting salt requirement in the range of 3-20%. There is significant
      diversity among halophiles from saline habitats of India. Preliminary
      characterization of crude hydrolases established them to be active and stable
      under more than one extreme condition of high salt, pH, temperature and presence
      of organic solvents. It is concluded that these halophilic isolates are not only
      diverse in phylogeny but also in their enzyme characteristics. Their enzymes may
      be potentially useful for catalysis under harsh operational conditions
      encountered in industrial processes. The solvent stability among halophilic
      enzymes seems a generic novel feature making them potentially useful in non
      aqueous enzymology. 

PMID- 24031992
TI  - Phenotypic diversity and amylolytic activity of fast growing rhizobia from
      pigeonpea [Cajanus cajan (L.) Millsp].
AB  - This study evaluated 26 pigeonpea rhizobial isolates according to their cultural
      characteristics, intrinsic antibiotic resistance, salt and temperature tolerance,
      carbon source utilization and amylolytic activity. The cultural characterization
      showed that the majority of them presented the ability to acidify the YMA. Among
      the 27 isolates evaluated, 25 were able to grow when incubated at 42 degrees  C
      and 11 showed tolerance to 3% (w/v) of NaCl in YMA medium. The patterns of carbon
      sources utilization was very diverse among the isolates. It was observed the
      capacity of three strains to metabolize all the carbon sources evaluated and a
      total of 42% of the bacterial isolates was able to grow in the culture medium
      supplemented with at least, six carbon sources. The carbon sources mannitol
      (control) and sucrose were metabilized by all isolates evaluated. The profile of
      intrinsic resistance to antibiotics showed that the isolates were mostly
      resistant to streptomycin and ampicillin, but susceptible to kanamycin and
      chloranphenicol. High amylolytic activity of, at least, four isolates was also
      demonstrated, especially for isolated 47.3b, which showed the highest enzymatic
      index. These results indicate the metabolic versatility of the pigeonpea
      rhizobia, and indicates the isolate 47.3b to further studies regarding the
      amylase production and characterization. 

PMID- 24031993
TI  - Levan from Bacillus subtilis Natto: its effects in normal and in streptozotocin
      diabetic rats.
AB  - Levan is an exopolysaccharide of fructose primarily linked by beta-(2->6)
      glycosidic bonds with some beta-(2->1) branched chains. Due to its chemical
      properties, levan has possible applications in both the food and pharmaceutical
      industries. Bacillus subtilis is a promising industrial levan producer, as it
      ferments sucrose and has a high levan-formation capacity. A new strain of B.
      subtilis was recently isolated from Japanese food natto, and it has produced
      levan in large quantities. For future pharmaceutical applications, this study
      aimed to investigate the effects of levan produced by B. subtilis Natto, mainly
      as potential hypoglycemic agent, (previously optimized with a molecular weight
      equal to 72.37 and 4,146 kDa) in Wistar male rats with diabetes induced by
      streptozotocin and non-diabetic rats and to monitor their plasma cholesterol and
      triacylglycerol levels. After 15 days of experimentation, the animals were
      sacrificed, and their blood samples were analyzed. The results, compared using
      analysis of variance, demonstrated that for this type of levan, a hypoglycemic
      effect was not observed, as there was no improvement of diabetes symptoms during
      the experiment. However, levan did not affect any studied parameters in normal
      rats, indicating that the exopolysaccharide can be used for other purposes. 

PMID- 24031994
TI  - Heavy metal tolerance (Cr, Ag AND Hg) in bacteria isolated from sewage.
AB  - Samples of sewage from a university hospital and a chemistry technical school
      were analysed for the percentage of bacterial tolerance to chromium (Cr), silver
      (Ag) and mercury (Hg). Additionally, we investigated the effect of these metals
      on pigmentation and on some enzymatic activities of the metal tolerant strains
      isolated, as well as antimicrobial resistance in some metal tolerant
      Enterobacteriaceae strains. Tolerance to Cr was observed mainly in Gram positive
      bacteria while in the case of Ag and Hg the tolerant bacteria were predominately
      Gram negative. Hg was the metal for which the percentage of tolerance was
      significantly higher, especially in samples from the hospital sewage (4.1%).
      Mercury also had the most discernible effect on color of the colonies.
      Considering the effect of metals on the respiratory enzymes, one strain of Ag
      tolerant Bacillus sp. and one of Hg-tolerant P. aeruginosa were unable to produce
      oxidase in the presence of Ag and Hg, respectively, while the expression of
      gelatinase was largely inhibited in various Gram negative strains (66% by Cr).
      Drug resistance in Hg-tolerant Enterobacteriaceae strains isolated from the
      university hospital sewage was greater than 80%, with prevalence of multiple
      resistance, while the Ag-tolerant strains from the same source showed about 34%
      of resistance, with the predominance of mono-resistance. Our results showed that,
      despite the ability of metal tolerant strains to survive and grow in the presence
      of these elements, the interactions with these metals may result in metabolic or
      phisiological changes in this group of bacteria. 

PMID- 24031995
TI  - Pseudorabies virus can be classified into five genotypes using partial sequences
      of UL44.
AB  - Suid herpesvirus 1 (SuHV-1) is the causative agent of pseudorabies (PR), a
      disease of great importance due to the huge losses it causes in the swine
      industry. The aim of this study was to determine a method for genotyping SuHV-1
      based on partial sequences of the gene coding for glycoprotein C (gC) and to
      elucidate the possible reasons for the variability of this region. A total of 109
      gCsequences collected from GenBank were divided into five major groups after
      reconstruction of a phylogenetic tree by Bayesian inference. The analysis showed
      that a portion of gC (approximately 671 bp) is under selective pressure at
      various points that coincide with regions of protein disorder. It was also
      possible to divide SuHV-1 into five genotypes that evolved under different
      selective pressures. These genotypes are not specific to countries or continents,
      perhaps due to multiple introduction events related to the importation of swine. 

PMID- 24031996
TI  - Human rhinovirus infections in symptomatic and asymptomatic subjects.
AB  - The role of rhinovirus asymptomatic infections in the transmission among close
      contacts subjects is unknown. We tested health care workers, a pair of one child
      and a family member and immunocompromised patients (n =191). HRV were detected on
      22.9% symptomatic and 3.6% asymptomatic cases suggesting lower transmission among
      contacts. 

PMID- 24031997
TI  - Molecular epidemiology of Staphylococcus aureus isolates at different sites in
      the milk producing dairy farms.
AB  - The epidemiological relationships between isolated Staphylococcus aureus strains
      in milk samples of dairy cows, reagent to California Mastitis Test, individual
      and group milk was demonstrated in different sites of the production fluxogram,
      in 12 milk-producing farms in the Gameleira region, municipality of Sacramento MG
      Brazil, so that localization and transmission modes may be identified. Two
      hundred and forty-four strains out of 446 samples collected at several sites were
      isolated and bio-chemically characterized as coagulase-positive staphylococcus.
      Specific chromosome DNA fragment of the species Staphylococcus aureus was
      amplified to 106 strains and 103 underwent (PFGE). Samples' collection sites with
      the highest isolation frequency of Staphylococcus aureus strains comprised
      papillary ostia (31.1%), CMT-reagent cow milk (21.7%), mechanical milking
      machines' insufflators (21,7%), milk in milk pails (6.6%) and the milk in
      community bulk tanks (5.6%). Genetic heterogeneity existed among the isolated 103
      Staphylococcus aureus strains, since 32 different pulse-types were identified.
      Pulse-type 1 had the highest similarity among the isolated strains within the
      different sites of the milk-production fluxogram. Highest occurrence of pulsetype
      1 isolates of Staphylococcus aureus strains was reported in samples collected
      from the papillary ostia (10.6%), followed by milk samples from CMT-reagent dairy
      cows (5.8%) and mechanical milking machine insufflators (3.8%). The above shows
      the relevance of these sites in the agents' transmission mechanism within the
      context of the farms investigated. 

PMID- 24031998
TI  - Quantifying the Benefits of Link-Tracing Designs for Partnership Network Studies.
AB  - Difficult-to-reach populations are frequently sampled through various link
      tracing based designs, which rely on interpersonal networks to identify members
      of the population. This article examines the substantive returns to one such
      multiple-link tracing design in the Colorado Springs "Project 90" HIV risk
      networks study. Cross-links were respondents who were targeted for enrollment
      because of being named as partners by at least two other respondents in the
      sample. We compare cross-links to other respondents on sociodemographic
      characteristics and network properties using bivariate and multivariate adjusted
      statistics. We evaluate their contributions to observed network structure by
      creating a set of counterfactual networks deleting the information they provided.
      Results suggest that the link-tracing techniques led to identifying populations
      that would have otherwise been missed and that their absence would have
      underestimated potential HIV risk by distorting epidemiologically relevant
      measures within the network.

PMID- 24031999
TI  - Patients Can Accurately Perform Their Own Rapid HIV Point-of-Care Test in the
      Emergency Department.
AB  - OBJECTIVE: The objective of this study was to evaluate the feasibility,
      acceptability, and accuracy of having emergency department (ED) patients perform
      a rapid, point-of-care (POC) self-test for HIV before routine HIV testing.
      METHODS: Patients aged 18 to 65 years were recruited to perform a rapid POC HIV
      oral fluid at The Johns Hopkins ED in conjunction with the standard-of-care HIV
      POC test. Acceptability and ease of use were assessed by a questionnaire.
      RESULTS: A total of 259 patients were approached for testing, and 249 (96.1%)
      consented to perform a self POC HIV test. Of patients performing a self-test,
      100% had concordant results with those obtained by the health care worker. Four
      females (1.6%) were newly identified as HIV positive. Median participant age was
      41 years, and 58% of patients were female; 83% were African American, and 16%
      were white. Overall, greater than 90% of patients reported trust of the test
      results, ease of testing, and willingness to test again. Approximately 35% of
      patients indicated they would pay up to a maximum price of $30 for testing.
      Overall, 46.9% of patients preferred self-testing, and 39.5% preferred health
      care professional testing. Regarding preferred location for testing, 51.0%
      preferred home self-testing, 39.5% preferred clinic/ED self-testing (P > 0.05),
      and 9.5% had no preference. CONCLUSIONS: A significant proportion of patients
      offered POC testing in the ED agreed to perform a self-HIV test. Patients'
      results were concordant with those obtained by the health care worker; 1.6% were
      HIV positive. The majority of participants believed the veracity of their
      results. A greater number of patients preferred self-testing.

PMID- 24032000
TI  - The IDEA (International Duration Evaluation of Adjuvant Chemotherapy)
      Collaboration: Prospective Combined Analysis of Phase III Trials Investigating
      Duration of Adjuvant Therapy with the FOLFOX (FOLFOX4 or Modified FOLFOX6) or
      XELOX (3 versus 6 months) Regimen for Patients with Stage III Colon Cancer: Trial
      Design and Current Status.
AB  - The International Duration Evaluation of Adjuvant Chemotherapy (IDEA)
      collaboration was established to prospectively combine and analyze data from
      several randomized trials conducted around the world to answer whether a three
      month course of oxaliplatin-based adjuvant therapy (FOLFOX4/modified FOLFOX6 or
      XELOX) is non-inferior to the current standard six-month treatment for patients
      with stage III colon cancer, with a primary endpoint of three years disease-free
      survival. The IDEA steering committee comprises two members from each group
      coordinating an individual trial and two members from a secretariat who
      coordinate combining of the data and management of the joint analysis. Members of
      the IDEA agreed to combine the data from their individual trials to enable
      definitive analysis consisting of at least 10,500 patients. With accrual of 8,797
      patients at the end of February 2013, the IDEA is on track to achieve its accrual
      objective of at least 10,500 patients by the end of 2013.

PMID- 24032001
TI  - Correcting the Results of the Wrong Model: Treatment Effects under Early
      Detection of Cancer.
AB  - Early detection of cancer leads to variability of the point of diagnosis advanced
      by the amount of the so-called lead time, a random variable. Estimated treatment
      effects by the proportional hazards (PH) model may be biased if this variability
      is ignored. We study how true and PH-estimated treatment effects differ in
      screened vs. unscreened populations and offer an approximate correction for the
      reported PH-based estimate that does not require raw data, targeting a meta
      analysis-type application. We rely on a joint cancer incidence and survival model
      of prostate cancer to furnish key information for the correction. The procedure
      is applied to a series of prostate cancer data analyses using the PH models
      reported in the literature. Simulations are used for assessing the quality of the
      method and sensitivity analyses.

PMID- 24032002
TI  - Gold (III) Chloride-Catalyzed 6-endo-trig Oxa-Michael Addition Reactions for
      Diastereoselective Synthesis of Fused Tetrahydropyranones.
AB  - Alkynones were treated with boron trifluoride diethyl etherate to generate beta
      iodoallenolates, which underwent intramolecular aldol reactions to produce
      cycloalkenyl alcohols. Diastereoselective oxa-Michael ring closure could then be
      induced by treatment with a catalytic amount of gold(III) chloride, affording
      highly functionalized tetrahydropyran-containing ring systems.

PMID- 24032003
TI  - Hematological profile of East African short-horn zebu calves from birth to 51
      weeks of age.
AB  - This paper is the first attempt to accurately describe the hematological
      parameters for any African breed of cattle, by capturing the changes in these
      parameters over the first 12 months of an animal's life using a population-based
      sample of calves reared under field conditions and natural disease challenge.
      Using a longitudinal study design, a stratified clustered random sample of
      newborn calves was recruited into the IDEAL study and monitored at 5-weekly
      intervals until 51 weeks of age. The blood cell analysis performed at each visit
      included: packed cell volume; red cell count; red cell distribution width; mean
      corpuscular volume; mean corpuscular hemoglobin concentration; hemoglobin
      concentration; white cell count; absolute lymphocyte, eosinophil, monocyte, and
      neutrophil counts; platelet count; mean platelet volume; and total serum protein.
      The most significant age-related change in the red cell parameters was a rise in
      red cell count and hemoglobin concentration during the neonatal period. This is
      in contrast to what is reported for other ruminants, including European cattle
      breeds where the neonatal period is marked by a fall in the red cell parameters.
      There is a need to establish breed-specific reference ranges for blood parameters
      for indigenous cattle breeds. The possible role of the postnatal rise in the red
      cell parameters in the adaptability to environmental constraints and innate
      disease resistance warrants further research into the dynamics of blood cell
      parameters of these breeds.

PMID- 24032004
TI  - The Demography of Canada and the United States from the 1980s to the 2000s A
      Summary of Changes and a Statistical Assessment.
AB  - Canada and the United States have enjoyed vigorous population growth since the
      early 1980s. Although mortality is slightly higher in the United States than in
      Canada, this is largely offset by much higher fertility, with a total fertility
      rate at replacement level, compared with just 1.5 children per woman in Canada.
      The United States is also the world's largest immigrant receiving country,
      although its immigration rate is only half that of Canada, where today one person
      in five is foreign-born, versus one in eight in the United States. Based on
      recent trends in fertility, mortality and international migration, the
      populations of these two North American countries will continue to grow over the
      next five decades, but at a progressively slower pace. The most acute demographic
      issue today is not, as in Europe, that of imminent population decline, but rather
      of the geographic and social inequalities which have increased steadily since the
      early 1980s and which are reflected in major fertility and health differentials
      between regions and social groups.

PMID- 24032005
TI  - The human cerebral cortex is neither one nor many: neuronal distribution reveals
      two quantitatively different zones in the gray matter, three in the white matter,
      and explains local variations in cortical folding.
AB  - The human prefrontal cortex has been considered different in several aspects and
      relatively enlarged compared to the rest of the cortical areas. Here we determine
      whether the white and gray matter of the prefrontal portion of the human cerebral
      cortex have similar or different cellular compositions relative to the rest of
      the cortical regions by applying the Isotropic Fractionator to analyze the
      distribution of neurons along the entire anteroposterior axis of the cortex, and
      its relationship with the degree of gyrification, number of neurons under the
      cortical surface, and other parameters. The prefrontal region shares with the
      remainder of the cerebral cortex (except for occipital cortex) the same
      relationship between cortical volume and number of neurons. In contrast, both
      occipital and prefrontal areas vary from other cortical areas in their
      connectivity through the white matter, with a systematic reduction of cortical
      connectivity through the white matter and an increase of the mean axon caliber
      along the anteroposterior axis. These two parameters explain local differences in
      the distribution of neurons underneath the cortical surface. We also show that
      local variations in cortical folding are neither a function of local numbers of
      neurons nor of cortical thickness, but correlate with properties of the white
      matter, and are best explained by the folding of the white matter surface. Our
      results suggest that the human cerebral cortex is divided in two zones (occipital
      and non-occipital) that differ in how neurons are distributed across their gray
      matter volume and in three zones (prefrontal, occipital, and non-occipital) that
      differ in how neurons are connected through the white matter. Thus, the human
      prefrontal cortex has the largest fraction of neuronal connectivity through the
      white matter and the smallest average axonal caliber in the white matter within
      the cortex, although its neuronal composition fits the pattern found for other,
      non-occipital areas. 

PMID- 24032006
TI  - Neuronal influence behind the central nervous system regulation of the immune
      cells.
AB  - Central nervous system (CNS) has a highly specialized microenvironment, and
      despite being initially considered an immune privileged site, this immune status
      is far from absolute because it varies with age and brain topography. The brain
      monitors immune responses by several means that act in parallel; one pathway
      involves afferent nerves (vagal nerve) and the other resident cells (neurons and
      glia). These cell populations exert a strong role in the regulation of the immune
      system, favoring an immune-modulatory environment in the CNS. Neurons control
      glial cell and infiltrated T-cells by contact-dependent and -independent
      mechanisms. Contact-dependent mechanisms are provided by several membrane immune
      modulating molecules such as Sema-7A, CD95L, CD22, CD200, CD47, NCAM, ICAM-5, and
      cadherins; which can inhibit the expression of microglial inflammatory cytokines,
      induce apoptosis or inactivate infiltrated T-cells. On the other hand, soluble
      neuronal factors like Sema-3A, cytokines, neurotrophins, neuropeptides, and
      neurotransmitters attenuate microglial and/or T-cell activation. In this review,
      we focused on all known mechanism driven only by neurons in order to control the
      local immune cells. 

PMID- 24032007
TI  - Applying independent component analysis to clinical FMRI at 7 t.
AB  - Increased BOLD sensitivity at 7 T offers the possibility to increase the
      reliability of fMRI, but ultra-high field is also associated with an increase in
      artifacts related to head motion, Nyquist ghosting, and parallel imaging
      reconstruction errors. In this study, the ability of independent component
      analysis (ICA) to separate activation from these artifacts was assessed in a 7 T
      study of neurological patients performing chin and hand motor tasks. ICA was able
      to isolate primary motor activation with negligible contamination by motion
      effects. The results of General Linear Model (GLM) analysis of these data were,
      in contrast, heavily contaminated by motion. Secondary motor areas, basal
      ganglia, and thalamus involvement were apparent in ICA results, but there was low
      capability to isolate activation in the same brain regions in the GLM analysis,
      indicating that ICA was more sensitive as well as more specific. A method was
      developed to simplify the assessment of the large number of independent
      components. Task-related activation components could be automatically identified
      via these intuitive and effective features. These findings demonstrate that ICA
      is a practical and sensitive analysis approach in high field fMRI studies,
      particularly where motion is evoked. Promising applications of ICA in clinical
      fMRI include presurgical planning and the study of pathologies affecting
      subcortical brain areas. 

PMID- 24032008
TI  - Temporal hemodynamic classification of two hands tapping using functional near
      infrared spectroscopy.
AB  - In recent decades, a lot of achievements have been obtained in imaging and
      cognitive neuroscience of human brain. Brain's activities can be shown by a
      number of different kinds of non-invasive technologies, such as: Near-Infrared
      Spectroscopy (NIRS), Magnetic Resonance Imaging (MRI), and ElectroEncephaloGraphy
      (EEG; Wolpaw et al., 2002; Weiskopf et al., 2004; Blankertz et al., 2006). NIRS
      has become the convenient technology for experimental brain purposes. The change
      of oxygenation changes (oxy-Hb) along task period depending on location of
      channel on the cortex has been studied: sustained activation in the motor cortex,
      transient activation during the initial segments in the somatosensory cortex, and
      accumulating activation in the frontal lobe (Gentili et al., 2010). Oxy-Hb
      concentration at the aforementioned sites in the brain can also be used as a
      predictive factor allows prediction of subject's investigation behavior with a
      considerable degree of precision (Shimokawa et al., 2009). In this paper, a study
      of recognition algorithm will be described for recognition whether one taps the
      left hand (LH) or the right hand (RH). Data with noises and artifacts collected
      from a multi-channel system will be pre-processed using a Savitzky-Golay filter
      for getting more smoothly data. Characteristics of the filtered signals during LH
      and RH tapping process will be extracted using a polynomial regression (PR)
      algorithm. Coefficients of the polynomial, which correspond to Oxygen-Hemoglobin
      (Oxy-Hb) concentration, will be applied for the recognition models of hand
      tapping. Support Vector Machines (SVM) will be applied to validate the obtained
      coefficient data for hand tapping recognition. In addition, for the objective of
      comparison, Artificial Neural Networks (ANNs) was also applied to recognize hand
      tapping side with the same principle. Experimental results have been done many
      trials on three subjects to illustrate the effectiveness of the proposed method. 

PMID- 24032009
TI  - Neural networks underlying contributions from semantics in reading aloud.
AB  - Reading is an essential part of contemporary society, yet much is still unknown
      about the physiological underpinnings of its information processing components.
      Two influential cognitive models of reading, the connectionist and dual-route
      cascaded models, offer very different accounts, yet evidence for one or the other
      remains equivocal. These models differ in several ways, including the role of
      semantics (word meaning) in mapping spelling to sound. We used a new effective
      connectivity algorithm, IMaGES, to provide a network-level perspective on these
      network-level models. Left hemisphere regions of interest were defined based on
      main effects in functional magnetic resonance imaging and included two regions
      linked with semantic processing-angular gyrus (AG) and inferior temporal sulcus
      (ITS)-and two regions linked with phonological processing-posterior superior
      temporal gyrus (pSTG) and posterior middle temporal gyrus (pMTG). Participants
      read aloud words of high or low spelling-sound consistency, word frequency, and
      imageability. Only the connectionist model predicted increased contributions from
      semantic areas with those computing phonology for low-consistency words.
      Effective connectivity analyses revealed that areas supporting semantic
      processing (e.g., the ITS) interacted with phonological areas (e.g., the pSTG),
      with the pattern changing as a function of word properties. Connectivity from
      semantic to phonological areas emerged for high- compared to low-imageability
      words, and a similar pattern emerged for low-consistency words, though only under
      certain conditions. Analyses of individual differences also showed that variation
      in the strength of modulation of ITS by AG was associated with reading aloud
      performance. Overall, these results suggest that connections with semantic
      processing areas are not only associated with reading aloud, but that these
      connections are also associated with optimal reading performance. 

PMID- 24032010
TI  - Decreased small-world functional network connectivity and clustering across
      resting state networks in schizophrenia: an fMRI classification tutorial.
AB  - Functional network connectivity (FNC) is a method of analyzing the temporal
      relationship of anatomical brain components, comparing the synchronicity between
      patient groups or conditions. We use functional-connectivity measures between
      independent components to classify between Schizophrenia patients and healthy
      controls during resting-state. Connectivity is measured using a variety of graph
      theoretic connectivity measures such as graph density, average path length, and
      small-worldness. The Schizophrenia patients showed significantly less clustering
      (transitivity) among components than healthy controls (p < 0.05, corrected) with
      networks less likely to be connected, and also showed lower small-world
      connectivity than healthy controls. Using only these connectivity measures, an
      SVM classifier (without parameter tuning) could discriminate between
      Schizophrenia patients and healthy controls with 65% accuracy, compared to 51%
      chance. This implies that the global functional connectivity between resting
      state networks is altered in Schizophrenia, with networks more likely to be
      disconnected and behave dissimilarly for diseased patients. We present this
      research finding as a tutorial using the publicly available COBRE dataset of 146
      Schizophrenia patients and healthy controls, provided as part of the 1000
      Functional Connectomes Project. We demonstrate preprocessing, using independent
      component analysis (ICA) to nominate networks, computing graph-theoretic
      connectivity measures, and finally using these connectivity measures to either
      classify between patient groups or assess between-group differences using formal
      hypothesis testing. All necessary code is provided for both running command-line
      FSL preprocessing, and for computing all statistical measures and SVM
      classification within R. Collectively, this work presents not just findings of
      diminished FNC among resting-state networks in Schizophrenia, but also a
      practical connectivity tutorial. 

PMID- 24032011
TI  - Effect of eye patching in rehabilitation of hemispatial neglect.
AB  - Eye patching (EP; monocular or right hemifield) has been proposed to improve
      visuospatial attention to the ignored field in patients with hemispatial neglect.
      The aim of this paper is to review the literature on the effects of EP in
      hemispatial neglect after stroke in order to convey evidence-based
      recommendations to clinicians in stroke rehabilitation. Thirteen intervention
      studies were selected from the Medline, EMBASE, Scopus, Cochrane Library, CINAHL,
      PsychINFO, EBRSR, and Health Star databases. Methodological quality was defined
      according to the Physiotherapy Evidence Database. Overall, seven studies used
      monocular EP, five used right hemifield patching, and one compared right
      monocular with right hemifield patching. Seven studies compared normal viewing to
      monocular or hemifield patching conditions. Six studies included a period of
      treatment. As to the monocular EP, four studies reported positive effects of
      right monocular patching. One study showed an improvement in hemispatial neglect
      with left monocular patching. Two studies found no superiority of right vs. left
      monocular patching. One study found no effects of right monocular patching. As to
      the right hemifield EP, one study showed improvements in neglect after right
      hemifield patching. Three studies found that right hemifield patching combined
      with another rehabilitation technique was more effective than that treatment
      alone. One study found no differences between right hemifield patching combined
      with another treatment and that treatment alone. One study found the same effect
      between right hemifield patching alone and another rehabilitation technique. Our
      results globally tend to support the usefulness of right hemifield EP in clinical
      practice. In order to define a level of evidence with the standard rehabilitation
      evidence rating tools, further properly powered randomized controlled trials or
      meta-analysis are needed. 

PMID- 24032012
TI  - Human brain stem structures respond differentially to noxious heat.
AB  - Concerning the physiological correlates of pain, the brain stem is considered to
      be one core region that is activated by noxious input. In animal studies,
      different slopes of skin heating (SSH) with noxious heat led to activation in
      different columns of the midbrain periaqueductal gray (PAG). The present study
      aimed at finding a method for differentiating structures in PAG and other brain
      stem structures, which are associated with different qualities of pain in humans
      according to the structures that were associated with different behavioral
      significances to noxious thermal stimulation in animals. Brain activity was
      studied by functional MRI in healthy subjects in response to steep and shallow
      SSH with noxious heat. We found differential activation to different SSH in the
      PAG and the rostral ventromedial medulla (RVM). In a second experiment, we
      demonstrate that the different SSH were associated with different pain qualities.
      Our experiments provide evidence that brainstem structures, i.e., the PAG and the
      RVM, become differentially activated by different SSH. Therefore, different SSH
      can be utilized when brain stem structures are investigated and when it is aimed
      to activate these structures differentially. Moreover, percepts of first pain
      were elicited by shallow SSH whereas percepts of second pain were elicited by
      steep SSH. The stronger activation of these brain stem structures to SSH,
      eliciting percepts of second vs. first pain, might be of relevance for activating
      different coping strategies in response to the noxious input with the two types
      of SSH. 

PMID- 24032013
TI  - A Philosophical Perspective on the Relation between Cortical Midline Structures
      and the Self.
AB  - In recent years there has been increasing evidence that an area in the brain
      called the cortical midline structures (CMSs) is implicated in what has been
      termed self-related processing. This article will discuss recent evidence for the
      relation between CMS and self-consciousness in light of several important
      philosophical distinctions. First, we should distinguish between being a self
      (i.e., being a subject of conscious experience) and being aware of being a self
      (i.e., being able to think about oneself as such). While the former consists in
      having a first-person perspective on the world, the latter requires the ability
      to explicitly represent one's own perspective as such. Further, we should
      distinguish between being aware of oneself "as subject" and being aware of
      oneself "as object." The focus of existing studies investigating the relation
      between CMS and self has been predominantly on the ability to think about oneself
      (and in particular thinking of oneself "as object"), while the more basic aspects
      involved in being a self have been neglected. However, it is important to widen
      the scope of the cognitive neuroscience to include the latter, not least because
      this might have important implications for a better understanding of disorders of
      the self, such as those involved in schizophrenia. In order to do so, cognitive
      neuroscience should work together with philosophy, including phenomenology.
      Second, we need to distinguish between personal and subpersonal level
      explanations. It will be argued that although it is important to respect this
      distinction, in principle, some subpersonal facts can enter into constitutive
      conditions of personal-level phenomena. However, in order for this to be
      possible, one needs both careful conceptual analysis and knowledge about relevant
      cognitive mechanisms. 

PMID- 24032015
TI  - Learning to never forget-time scales and specificity of long-term memory of a
      motor skill.
AB  - Despite anecdotal reports that humans retain acquired motor skills for many
      years, if not a lifetime, long-term memory of motor skills has received little
      attention. While numerous neuroimaging studies showed practice-induced cortical
      plasticity, the behavioral correlates, what is retained and also what is
      forgotten, are little understood. This longitudinal case study on four subjects
      presents detailed kinematic analyses of humans practicing a bimanual polyrhythmic
      task over 2 months with retention tests after 6 months and, for two subjects,
      after 8 years. Results showed that individuals not only retained the task, but
      also reproduced their individual "style" of performance, even after 8 years.
      During practice, variables such as the two hands' frequency ratio and relative
      phase, changed at different rates, indicative of multiple time scales of neural
      processes. Frequency leakage across hands, reflecting intermanual crosstalk,
      attenuated at a significantly slower rate and was the only variable not
      maintained after 8 years. Complementing recent findings on neuroplasticity in
      gray and white matter, our study presents new behavioral evidence that highlights
      the multi-scale process of practice-induced changes and its remarkable
      persistence. Results suggest that motor memory may comprise not only higher-level
      task variables but also individual kinematic signatures. 

PMID- 24032014
TI  - Hemispheric lateralization interrupted: material-specific memory deficits in
      temporal lobe epilepsy.
AB  - The hemispheric lateralization of memory has largely been informed through the
      study of patients with temporal lobe epilepsy originating from medial temporal
      sources (mTLE). The material-specific model of memory relies on the basic
      framework that the left temporal lobe mediates verbal memories, while the right
      temporal lobe mediates non-verbal memories. Over the years, this model has been
      refined, and even challenged, as our understanding of the material-specific
      memory deficits in mTLE has been further elaborated in the neuropsychological and
      neuroimaging literature. The first goal of this mini-review is to highlight the
      major findings in the mTLE literature that have advanced and expanded our
      understanding of material-specific memory deficits in mTLE. Second, we will
      review how functional neuroimaging patterns of material-specific hemispheric
      lateralization in mTLE are being translated into the innovative clinical
      application of preoperative fMRI memory mapping. 

PMID- 24032016
TI  - Plasticity and modular control of locomotor patterns in neurological disorders
      with motor deficits.
AB  - Human locomotor movements exhibit considerable variability and are highly complex
      in terms of both neural activation and biomechanical output. The building blocks
      with which the central nervous system constructs these motor patterns can be
      preserved in patients with various sensory-motor disorders. In particular,
      several studies highlighted a modular burst-like organization of the muscle
      activity. Here we review and discuss this issue with a particular emphasis on the
      various examples of adaptation of locomotor patterns in patients (with large
      fiber neuropathy, amputees, stroke and spinal cord injury). The results highlight
      plasticity and different solutions to reorganize muscle patterns in both
      peripheral and central nervous system lesions. The findings are discussed in a
      general context of compensatory gait mechanisms, spatiotemporal architecture and
      modularity of the locomotor program. 

PMID- 24032018
TI  - Semantic organization in children with cochlear implants: computational analysis
      of verbal fluency.
AB  - PURPOSE: Cochlear implants (CIs) enable children with severe and profound hearing
      impairments to perceive the sensation of sound sufficiently to permit oral
      language acquisition. So far, studies have focused mainly on technological
      improvements and general outcomes of implantation for speech perception and
      spoken language development. This study quantitatively explored the organization
      of the semantic networks of children with CIs in comparison to those of age
      matched normal hearing (NH) peers. METHOD: Twenty seven children with CIs and
      twenty seven age- and IQ-matched NH children ages 7-10 were tested on a timed
      animal verbal fluency task (Name as many animals as you can). The responses were
      analyzed using correlation and network methodologies. The structure of the animal
      category semantic network for both groups were extracted and compared. RESULTS:
      Children with CIs appeared to have a less-developed semantic network structure
      compared to age-matched NH peers. The average shortest path length (ASPL) and the
      network diameter measures were larger for the NH group compared to the CIs group.
      This difference was consistent for the analysis of networks derived from animal
      names generated by each group [sample-matched correlation networks (SMCN)] and
      for the networks derived from the common animal names generated by both groups
      [word-matched correlation networks (WMCN)]. CONCLUSIONS: The main difference
      between the semantic networks of children with CIs and NH lies in the network
      structure. The semantic network of children with CIs is under-developed compared
      to the semantic network of the age-matched NH children. We discuss the practical
      and clinical implications of our findings.

PMID- 24032019
TI  - Why are there different types of synesthete?

PMID- 24032017
TI  - Deficient Suppression of Default Mode Regions during Working Memory in
      Individuals with Early Psychosis and at Clinical High-Risk for Psychosis.
AB  - BACKGROUND: The default mode network (DMN) is a set of brain regions typically
      activated at rest and suppressed during extrinsic cognition. Schizophrenia has
      been associated with deficient DMN suppression, though the extent to which DMN
      dysfunction predates psychosis onset is unclear. This study examined DMN
      suppression during working memory (WM) performance in youth at clinical high-risk
      (CHR) for psychosis, early schizophrenia (ESZ) patients, and healthy controls
      (HC). We hypothesized that the DMN would show load-dependent suppression during
      WM retrieval in HC but not in ESZ, with CHR participants showing an intermediate
      pattern. METHODS: fMRI data were collected from CHR (n = 32), ESZ (n = 22), and
      HC (n = 54) participants, ages 12-30. DMN regions were defined via seed-based
      connectivity analysis of resting-state fMRI data from an independent HC sample.
      Load-dependent deactivations of these DMN regions in response to WM probes were
      interrogated. RESULTS: Healthy controls showed linear load-dependent increases in
      DMN deactivation. Significant Group-by-Load interactions were observed in DMN
      regions including medial prefrontal and lateral posterior parietal cortices.
      Group-by-Load effects in posterior DMN nodes resulted from less suppression at
      higher WM loads in ESZ relative to HC, with CHR differing from neither group. In
      medial prefrontal cortex, suppression of activity at higher WM loads was
      significantly diminished in both CHR and ESZ groups, relative to HC. In addition,
      investigation of dorsolateral prefrontal cortex (DLPFC) activations revealed that
      ESZ activated right DLPFC significantly more than HC, with CHR differing from
      neither group. CONCLUSION: While HC showed WM load-dependent modulation of DMN
      suppression, CHR individuals had deficient higher-load DMN suppression that was
      similar to, but less pronounced than, the distributed suppression deficits
      evident in ESZ patients. These results suggest that DMN dysregulation associated
      with schizophrenia predates psychosis onset.

PMID- 24032020
TI  - Mind wandering via mental contrasting as a tool for behavior change.
AB  - When people engage in mind wandering they drift away from a task toward their
      inner thoughts and feelings. These thoughts often circle around people's personal
      futures. One assumed function of mind wandering is that it aids problem solving
      and planning for the future. We will discuss different forms of mind wandering
      and their effects on problem solving and behavior change. While solely
      fantasizing about a desired future leads to poor problem solving and little
      behavior change, mind wandering in the form of mental contrasting leads to
      skilled problem solving and substantial behavior change. In mental contrasting,
      people first envision the desired future and then imagine the obstacles that need
      to be surmounted to reach said future. Mental contrasting instigates behavior
      change by modulating the strength of associations between future and reality and
      between reality and instrumental action. Intervention research shows that mental
      contrasting can be taught as a cost- and time-effective self-regulation strategy
      of behavior change. The findings have implications for research on mind
      wandering, problem solving, and on creating effective interventions of behavior
      change. 

PMID- 24032021
TI  - Group rhythmic synchrony and attention in children.
AB  - Synchrony, or the coordinated processing of time, is an often-overlooked yet
      critical context for human interaction. This study tests the relationship between
      the ability to synchronize rhythmically in a group setting with the ability to
      attend in 102 elementary schoolchildren. Impairments in temporal processing have
      frequently been shown to exist in clinical populations with learning disorders,
      particularly those with Attention Deficit Hyperactivity Disorder (ADHD). Based on
      this evidence, we hypothesized that the ability to synchronize rhythmically in a
      group setting-an instance of the type of temporal processing necessary for
      successful interaction and learning-would be correlated with the ability to
      attend across the continuum of the population. A music class is an ideal setting
      for the study of interpersonal timing. In order to measure synchrony in this
      context, we constructed instruments that allowed the recording and measurement of
      individual rhythmic performance. The SWAN teacher questionnaire was used as a
      measurement of attentional behavior. We find that the ability to synchronize with
      others in a group music class can predict a child's attentional behavior. 

PMID- 24032023
TI  - Color and texture associations in voice-induced synesthesia.
AB  - Voice-induced synesthesia, a form of synesthesia in which synesthetic perceptions
      are induced by the sounds of people's voices, appears to be relatively rare and
      has not been systematically studied. In this study we investigated the
      synesthetic color and visual texture perceptions experienced in response to
      different types of "voice quality" (e.g., nasal, whisper, falsetto). Experiences
      of three different groups-self-reported voice synesthetes, phoneticians, and
      controls-were compared using both qualitative and quantitative analysis in a
      study conducted online. Whilst, in the qualitative analysis, synesthetes used
      more color and texture terms to describe voices than either phoneticians or
      controls, only weak differences, and many similarities, between groups were found
      in the quantitative analysis. Notable consistent results between groups were the
      matching of higher speech fundamental frequencies with lighter and redder colors,
      the matching of "whispery" voices with smoke-like textures, and the matching of
      "harsh" and "creaky" voices with textures resembling dry cracked soil. These data
      are discussed in the light of current thinking about definitions and
      categorizations of synesthesia, especially in cases where individuals apparently
      have a range of different synesthetic inducers. 

PMID- 24032022
TI  - Music and speech prosody: a common rhythm.
AB  - Disorders of music and speech perception, known as amusia and aphasia, have
      traditionally been regarded as dissociated deficits based on studies of brain
      damaged patients. This has been taken as evidence that music and speech are
      perceived by largely separate and independent networks in the brain. However,
      recent studies of congenital amusia have broadened this view by showing that the
      deficit is associated with problems in perceiving speech prosody, especially
      intonation and emotional prosody. In the present study the association between
      the perception of music and speech prosody was investigated with healthy Finnish
      adults (n = 61) using an on-line music perception test including the Scale
      subtest of Montreal Battery of Evaluation of Amusia (MBEA) and Off-Beat and Out
      of-key tasks as well as a prosodic verbal task that measures the perception of
      word stress. Regression analyses showed that there was a clear association
      between prosody perception and music perception, especially in the domain of
      rhythm perception. This association was evident after controlling for music
      education, age, pitch perception, visuospatial perception, and working memory.
      Pitch perception was significantly associated with music perception but not with
      prosody perception. The association between music perception and visuospatial
      perception (measured using analogous tasks) was less clear. Overall, the pattern
      of results indicates that there is a robust link between music and speech
      perception and that this link can be mediated by rhythmic cues (time and stress).

PMID- 24032024
TI  - Dieting and restrained eating as prospective predictors of weight gain.
AB  - Research in normal weight individuals paradoxically suggests that measures of
      attempted eating restriction might represent robust predictors of weight gain.
      This review examined the extent to which measures of dieting (e.g., self-reported
      weight loss dieting in the past year) and dietary restraint (e.g., the Cognitive
      Restraint scale from the Three-Factor Eating Questionnaire) have prospectively
      predicted weight change. We located and reviewed 25 prospective studies
      containing 40 relevant comparisons. Studies were limited to those in which
      participants were non-obese (with a mean BMI between 18.5 and 30) and averaged at
      least 12 years old. Neither measure predicted future weight loss. Fifteen of the
      20 comparisons (75%) that examined measures of dieting significantly predicted
      future weight gain whereas only 1 of 20 (5%) that examined restrained eating
      measures did so. Two plausible explanations for these findings are that: (1)
      dieters and restrained eaters do not differ in terms of an underlying proneness
      toward weight gain, but restrained eating represents a more effective means of
      preventing it; and (2) normal weight individuals who diet do so because they are
      resisting a powerful predisposition toward weight gain which dieting ultimately
      fails to prevent. Recent dieting in non-obese individuals may be a valuable proxy
      of susceptibility to weight gain. This easily assessed characteristic could
      identify individuals for whom obesity prevention interventions would be
      particularly appropriate. 

PMID- 24032025
TI  - Autoantibodies to Potassium Channel KIR4.1 in Multiple Sclerosis.

PMID- 24032026
TI  - EMLA-Induced Skin Wrinkling for the Detection of Diabetic Neuropathy.
AB  - OBJECTIVE: To determine the usefulness of Eutectic Mixture of Local Anesthetic
      (EMLA)-induced stimulated skin wrinkling (SSW) to detect diabetic sensorimotor
      polyneuropathy (DSPN). RESEARCH DESIGN AND METHODS: Two hundred and ten diabetics
      were prospectively recruited (mean age 58.5 +/- 12.7 years) from a large tertiary
      center from 2009 to 2011. EMLA was applied to the tips of digits 2, 3, and 4 and
      the degree of wrinkling graded. Diabetic Neuropathy Symptom (DNS) score, nerve
      conduction studies (NCS), Semmes-Weinstein monofilament (SWMF) tests, and
      vibratory perception thresholds (VPTs) testing were chosen as comparative
      clinical standards to diagnose length-dependent DSPN. RESULTS: Inter-rater
      agreement for two examiners of SSW was high, with Cohen's weighted kappa of 0.912
      for the right hand, and 0.823 for the left. K measure of agreement of SSW with
      the NCS, DNS scores, SWMF testing, and VPT testing was 0.486, 0.243, 0.289, and
      0.395 respectively. SSW was able to distinguish between normal and abnormal NCS
      and DNS results, with median scores of 3.333 vs. 1.667 (p < 0.0005); and 3.167
      vs. 2.000 (p < 0.0005) respectively. Following receiver operating characteristic
      analysis, at a cut-off point of <3 for an abnormal SSW test, sensitivity of SSW
      test for diagnosing DSPN using NCS as a reference standard was 81.3%, and
      specificity was 67.0%, on par with other testing methods. CONCLUSION: SSW shows
      comparable sensitivity to other methods for detecting DSPN. Given its low cost
      and easy administration, SSW can be considered a useful alternative screening
      method for diagnosing diabetic neuropathy.

PMID- 24032027
TI  - Fine tuning of the temporal expression of HTLV-1 and HTLV-2.
AB  - Human T-cell leukemia virus types 1 and 2 (HTLV-1 and HTLV-2) are delta
      retroviruses that share a common overall genetic organization, splicing pattern,
      and ability to infect and immortalize T-cells in vitro. However, HTLV-1 and HTLV
      2 exhibit a clearly distinct pathogenic potential in infected patients. To find
      clues to the possible viral determinants of the biology of these viruses, recent
      studies investigated the timing of expression and the intracellular
      compartmentalization of viral transcripts in ex-vivo samples from infected
      patients. Results of these studies revealed a common overall pattern of
      expression of HTLV-1 and -2 with a two-phase kinetics of expression and a nuclear
      accumulation of minus-strand transcripts. Studies in cells transfected with HTLV
      1 molecular clones demonstrated the strict Rex-dependency of this "two-phase"
      kinetics. These studies also highlighted interesting differences in the relative
      abundance of transcripts encoding the Tax and Rex regulatory proteins, and that
      of the accessory proteins controlling Rex expression and function, thus
      suggesting a potential basis for the different pathobiology of the two viruses. 

PMID- 24032028
TI  - Complete genome sequence and phenotype microarray analysis of Cronobacter
      sakazakii SP291: a persistent isolate cultured from a powdered infant formula
      production facility.
AB  - Outbreaks of human infection linked to the powdered infant formula (PIF) food
      chain and associated with the bacterium Cronobacter, are of concern to public
      health. These bacteria are regarded as opportunistic pathogens linked to life
      threatening infections predominantly in neonates, with an under developed immune
      system. Monitoring the microbiological ecology of PIF production sites is an
      important step in attempting to limit the risk of contamination in the finished
      food product. Cronobacter species, like other microorganisms can adapt to the
      production environment. These organisms are known for their desiccation
      tolerance, a phenotype that can aid their survival in the production site and PIF
      itself. In evaluating the genome data currently available for Cronobacter
      species, no sequence information has been published describing a Cronobacter
      sakazakii isolate found to persist in a PIF production facility. Here we report
      on the complete genome sequence of one such isolate, Cronobacter sakazakii SP291
      along with its phenotypic characteristics. The genome of C. sakazakii SP291
      consists of a 4.3-Mb chromosome (56.9% GC) and three plasmids, denoted as pSP291
      1, [118.1-kb (57.2% GC)], pSP291-2, [52.1-kb (49.2% GC)], and pSP291-3, [4.4-kb
      (54.0% GC)]. When C. sakazakii SP291 was compared to the reference C. sakazakii
      ATCC BAA-894, which is also of PIF origin, the annotated genome data identified
      two interesting functional categories, comprising of genes related to the
      bacterial stress response and resistance to antimicrobial and toxic compounds.
      Using a phenotypic microarray (PM), we provided a full metabolic profile
      comparing C. sakazakii SP291 and the previously sequenced C. sakazakii ATCC BAA
      894. These data extend our understanding of the genome of this important neonatal
      pathogen and provides further insights into the genotypes associated with
      features that can contribute to its persistence in the PIF environment. 

PMID- 24032030
TI  - Controls on soil microbial community stability under climate change.
AB  - Soil microbial communities are intricately linked to ecosystem functioning
      because they play important roles in carbon and nitrogen cycling. Still, we know
      little about how soil microbial communities will be affected by disturbances
      expected with climate change. This is a significant gap in understanding, as the
      stability of microbial communities, defined as a community's ability to resist
      and recover from disturbances, likely has consequences for ecosystem function.
      Here, we propose a framework for predicting a community's response to climate
      change, based on specific functional traits present in the community, the
      relative dominance of r- and K-strategists, and the soil environment. We
      hypothesize that the relative abundance of r- and K-strategists will inform about
      a community's resistance and resilience to climate change associated
      disturbances. We also propose that other factors specific to soils, such as
      moisture content and the presence of plants, may enhance a community's
      resilience. For example, recent evidence suggests microbial grazers, resource
      availability, and plant roots each impact on microbial community stability. We
      explore these hypotheses by offering three vignettes of published data that we re
      analyzed. Our results show that community measures of the relative abundance of r
      and K-strategists, as well as environmental properties like resource
      availability and the abundance and diversity of higher trophic levels, can
      contribute to explaining the response of microbial community composition to
      climate change-related disturbances. However, further investigation and
      experimental validation is necessary to directly test these hypotheses across a
      wide range of soil ecosystems. 

PMID- 24032029
TI  - Pathology of asthma.
AB  - Asthma is a serious health and socioeconomic issue all over the world, affecting
      more than 300 million individuals. The disease is considered as an inflammatory
      disease in the airway, leading to airway hyperresponsiveness, obstruction, mucus
      hyper-production and airway wall remodeling. The presence of airway inflammation
      in asthmatic patients has been found in the nineteenth century. As the
      information in patients with asthma increase, paradigm change in immunology and
      molecular biology have resulted in an extensive evaluation of inflammatory cells
      and mediators involved in the pathophysiology of asthma. Moreover, it is
      recognized that airway remodeling into detail, characterized by thickening of the
      airway wall, can be profound consequences on the mechanics of airway narrowing
      and contribute to the chronic progression of the disease. Epithelial to
      mesenchymal transition plays an important role in airway remodeling. These
      epithelial and mesenchymal cells cause persistence of the inflammatory
      infiltration and induce histological changes in the airway wall, increasing
      thickness of the basement membrane, collagen deposition and smooth muscle
      hypertrophy and hyperplasia. Resulting of airway inflammation, airway remodeling
      leads to the airway wall thickening and induces increased airway smooth muscle
      mass, which generate asthmatic symptoms. Asthma is classically recognized as the
      typical Th2 disease, with increased IgE levels and eosinophilic inflammation in
      the airway. Emerging Th2 cytokines modulates the airway inflammation, which
      induces airway remodeling. Biological agents, which have specific molecular
      targets for these Th2 cytokines, are available and clinical trials for asthma are
      ongoing. However, the relatively simple paradigm has been doubted because of the
      realization that strategies designed to suppress Th2 function are not effective
      enough for all patients in the clinical trials. In the future, it is required to
      understand more details for phenotypes of asthma. 

PMID- 24032033
TI  - Asymmetry of Cell Division in CFSE-Based Lymphocyte Proliferation Analysis.
AB  - Flow cytometry-based analysis of lymphocyte division using carboxyfluorescein
      succinimidyl ester (CFSE) dye dilution permits acquisition of data describing
      cellular proliferation and differentiation. For example, CFSE histogram data
      enable quantitative insight into cellular turnover rates by applying mathematical
      models and parameter estimation techniques. Several mathematical models have been
      developed using different types of deterministic or stochastic approaches.
      However, analysis of CFSE proliferation assays is based on the premise that the
      label is halved in the two daughter cells. Importantly, asymmetry of protein
      distribution in lymphocyte division is a basic biological feature of cell
      division with the degree of the asymmetry depending on various factors. Here, we
      review the recent literature on asymmetric lymphocyte division and CFSE-based
      lymphocyte proliferation analysis. We suggest that division- and label-structured
      mathematical models describing CFSE-based cell proliferation should take into
      account asymmetry and time-lag in cell proliferation. Utilization of improved
      modeling algorithms will permit straightforward quantification of essential
      parameters describing the performance of activated lymphocytes. 

PMID- 24032034
TI  - Better to light a candle than curse the darkness: illuminating spatial
      localization and temporal dynamics of rapid microbial growth in the rhizosphere.
AB  - The rhizosphere is a hotbed of microbial activity in ecosystems, fueled by carbon
      compounds from plant roots. Basic questions about the location and dynamics of
      plant-spurred microbial growth in the rhizosphere are difficult to answer with
      standard, destructive soil assays mixing a multitude of microbe-scale
      microenvironments in a single, often sieved, sample. Soil microbial biosensors
      designed with the luxCDABE reporter genes fused to a promoter of interest enable
      continuous imaging of the microbial perception of (and response to) environmental
      conditions in soil. We used the common soil bacterium Pseudomonas putida KT2440
      as host to plasmid pZKH2 containing a fusion between the strong constitutive
      promoter nptII and luxCDABE (coding for light-emitting proteins) from Vibrio
      fischeri. Experiments in liquid media demonstrated that high light production by
      KT2440/pZKH2 was associated with rapid microbial growth supported by high carbon
      availability. We applied the biosensors in microcosms filled with non-sterile
      soil in which corn (Zea mays L.), black poplar (Populus nigra L.), or tomato
      (Solanum lycopersicum L.) was growing. We detected minimal light production from
      microbiosensors in the bulk soil, but biosensors reported continuously from
      around roots for as long as six days. For corn, peaks of luminescence were
      detected 1-4 and 20-35 mm along the root axis behind growing root tips, with the
      location of maximum light production moving farther back from the tip as root
      growth rate increased. For poplar, luminescence around mature roots increased and
      decreased on a coordinated diel rhythm, but was not bright near root tips. For
      tomato, luminescence was dynamic, but did not exhibit a diel rhythm, appearing in
      acropetal waves along roots. KT2440/pZKH2 revealed that root tips are not always
      the only, or even the dominant, hotspots for rhizosphere microbial growth, and
      carbon availability is highly variable in space and time around roots. 

PMID- 24032032
TI  - The shape of the lymphocyte receptor repertoire: lessons from the B cell
      receptor.
AB  - Both the B cell receptor (BCR) and the T cell receptor (TCR) repertoires are
      generated through essentially identical processes of V(D)J recombination,
      exonuclease trimming of germline genes, and the random addition of non-template
      encoded nucleotides. The naive TCR repertoire is constrained by thymic selection,
      and TCR repertoire studies have therefore focused strongly on the diversity of
      MHC-binding complementarity determining region (CDR) CDR3. The process of somatic
      point mutations has given B cell studies a major focus on variable (IGHV, IGLV,
      and IGKV) genes. This in turn has influenced how both the naive and memory BCR
      repertoires have been studied. Diversity (D) genes are also more easily
      identified in BCR VDJ rearrangements than in TCR VDJ rearrangements, and this has
      allowed the processes and elements that contribute to the incredible diversity of
      the immunoglobulin heavy chain CDR3 to be analyzed in detail. This diversity can
      be contrasted with that of the light chain where a small number of polypeptide
      sequences dominate the repertoire. Biases in the use of different germline genes,
      in gene processing, and in the addition of non-template encoded nucleotides
      appear to be intrinsic to the recombination process, imparting "shape" to the
      repertoire of rearranged genes as a result of differences spanning many orders of
      magnitude in the probabilities that different BCRs will be generated. This may
      function to increase the precursor frequency of naive B cells with important
      specificities, and the likely emergence of such B cell lineages upon antigen
      exposure is discussed with reference to public and private T cell clonotypes. 

PMID- 24032031
TI  - Sweeten PAMPs: Role of Sugar Complexed PAMPs in Innate Immunity and Vaccine
      Biology.
AB  - Innate sensors play a critical role in the early innate immune responses to
      invading pathogens through sensing of diverse biochemical signatures also known
      as pathogen associated molecular patterns (PAMPs). These biochemical signatures
      primarily consist of a major family of biomolecules such as proteins, lipids,
      nitrogen bases, and sugar and its complexes, which are distinct from host
      molecules and exclusively expressed in pathogens and essential to their survival.
      The family of sensors known as pattern recognition receptors (PRRs) are germ-line
      encoded, evolutionarily conserved molecules, and consist of Toll-like receptors
      (TLRs), RIG-I-like receptors (RLRs), NOD-like receptors (NLRs), C-type lectin
      like receptors (CLRs), and DNA sensors. Sensing of PAMP by PRR initiates the
      cascade of signaling leading to the activation of transcription factors, such as
      NF-kappaB and interferon regulatory factors (IRFs), resulting in a variety of
      cellular responses, including the production of interferons (IFNs) and pro
      inflammatory cytokines. In this review, we discuss sensing of different types of
      glycosylated PAMPs such as beta-glucan (a polymeric sugar) or
      lipopolysaccharides, nucleic acid, and so on (sugar complex PAMPs) by different
      families of sensors, its role in pathogenesis, and its application in development
      of potential vaccine and vaccine adjuvants. 

PMID- 24032035
TI  - Morphological plasticity of ectomycorrhizal short roots in Betula sp and Picea
      abies forests across climate and forest succession gradients: its role in
      changing environments.
AB  - Morphological plasticity of ectomycorrhizal (EcM) short roots (known also as
      first and second order roots with primary development) allows trees to adjust
      their water and nutrient uptake to local environmental conditions. The
      morphological traits (MTs) of short-living EcM roots, such as specific root
      length (SRL) and area, root tip frequency per mass unit (RTF), root tissue
      density, as well as mean diameter, length, and mass of the root tips, are good
      indicators of acclimation. We investigated the role of EcM root morphological
      plasticity across the climate gradient (48-68 degrees N) in Norway spruce (Picea
      abies (L.) Karst) and (53-66 degrees N) birch (Betula pendula Roth., B. pubescens
      Ehrh.) forests, as well as in primary and secondary successional birch forests
      assuming higher plasticity of a respective root trait to reflect higher relevance
      of that characteristic in acclimation process. We hypothesized that although the
      morphological plasticity of EcM roots is subject to the abiotic and biotic
      environmental conditions in the changing climate; the tools to achieve the
      appropriate morphological acclimation are tree species-specific. Long-term (1994
      2010) measurements of EcM roots morphology strongly imply that tree species have
      different acclimation-indicative root traits in response to changing
      environments. Birch EcM roots acclimated along latitude by changing mostly SRL
      [plasticity index (PI) = 0.60], while spruce EcM roots became adjusted by
      modifying RTF (PI = 0.68). Silver birch as a pioneer species must have a broader
      tolerance to environmental conditions across various environments; however, the
      mean PI of all MTs did not differ between early-successional birch and late
      successional spruce. The differences between species in SRL, and RTF, diameter,
      and length decreased southward, toward temperate forests with more favorable
      growth conditions. EcM root traits reflected root-rhizosphere succession across
      forest succession stages. 

PMID- 24032037
TI  - A robust family of Golden Gate Agrobacterium vectors for plant synthetic biology.
AB  - Tools that allow for rapid, accurate and inexpensive assembly of multi-component
      combinatorial libraries of DNA for transformation into plants will accelerate the
      progress of synthetic biology research. Recent innovations in molecular cloning
      methods has vastly expanded the repertoire with which plant biologists can
      engineer a transgene. Here we describe a new set of binary vectors for use in
      Agrobacterium-mediated plant transformation that utilizes the Golden-Gate Cloning
      approach. Our optimized protocol facilitates the rapid and inexpensive generation
      of multi-component transgenes for later introduction into plants. 

PMID- 24032036
TI  - Iron economy in Chlamydomonas reinhardtii.
AB  - While research on iron nutrition in plants has largely focused on iron-uptake
      pathways, photosynthetic microbes such as the unicellular green alga
      Chlamydomonas reinhardtii provide excellent experimental systems for
      understanding iron metabolism at the subcellular level. Several paradigms in iron
      homeostasis have been established in this alga, including photosystem remodeling
      in the chloroplast and preferential retention of some pathways and key iron
      dependent proteins in response to suboptimal iron supply. This review presents
      our current understanding of iron homeostasis in Chlamydomonas, with specific
      attention on characterized responses to changes in iron supply, like iron
      deficiency. An overview of frequently used methods for the investigation of iron
      responsive gene expression, physiology and metabolism is also provided, including
      preparation of media, the effect of cell size, cell density and strain choice on
      quantitative measurements and methods for the determination of metal content and
      assessing the effect of iron supply on photosynthetic performance. 

PMID- 24032038
TI  - RuBisCO depletion improved proteome coverage of cold responsive S-nitrosylated
      targets in Brassica juncea.
AB  - Although in the last few years good number of S-nitrosylated proteins are
      identified but information on endogenous targets is still limiting. Therefore, an
      attempt is made to decipher NO signaling in cold treated Brassica juncea
      seedlings. Treatment of seedlings with substrate, cofactor and inhibitor of
      Nitric-oxide synthase and nitrate reductase (NR), indicated NR mediated NO
      biosynthesis in cold. Analysis of the in vivo thiols showed depletion of low
      molecular weight thiols and enhancement of available protein thiols, suggesting
      redox changes. To have a detailed view, S-nitrosylation analysis was done using
      biotin switch technique (BST) and avidin-affinity chromatography. Ribulose-1,5
      bisphosphate carboxylase/oxygenase (RuBisCO) is S-nitrosylated and therefore, is
      identified as target repeatedly due to its abundance. It also competes out low
      abundant proteins which are important NO signaling components. Therefore, RuBisCO
      was removed (over 80%) using immunoaffinity purification. Purified S-nitrosylated
      RuBisCO depleted proteins were resolved on 2-D gel as 110 spots, including 13
      new, which were absent in the crude S-nitrosoproteome. These were identified by
      nLC-MS/MS as thioredoxin, fructose biphosphate aldolase class I, myrosinase, salt
      responsive proteins, peptidyl-prolyl cis-trans isomerase and malate
      dehydrogenase. Cold showed differential S-nitrosylation of 15 spots, enhanced
      superoxide dismutase activity (via S-nitrosylation) and promoted the
      detoxification of superoxide radicals. Increased S-nitrosylation of
      glyceraldehyde-3-phosphate dehydrogenase sedoheptulose-biphosphatase, and
      fructose biphosphate aldolase, indicated regulation of Calvin cycle by S
      nitrosylation. The results showed that RuBisCO depletion improved proteome
      coverage and provided clues for NO signaling in cold. 

PMID- 24032039
TI  - The role and challenges of exome sequencing in studies of human diseases.
AB  - Recent advances in next-generation sequencing technologies have transformed the
      genetics study of human diseases; this is an era of unprecedented productivity.
      Exome sequencing, the targeted sequencing of the protein-coding portion of the
      human genome, has been shown to be a powerful and cost-effective method for
      detection of disease variants underlying Mendelian disorders. Increasing effort
      has been made in the interest of the identification of rare variants associated
      with complex traits in sequencing studies. Here we provided an overview of the
      application fields for exome sequencing in human diseases. We describe a general
      framework of computation and bioinformatics for handling sequencing data. We then
      demonstrate data quality and agreement between exome sequencing and exome
      microarray (chip) genotypes using data collected on the same set of subjects in a
      genetic study of panic disorder. Our results show that, in sequencing data, the
      data quality was generally higher for variants within the exonic target regions,
      compared to that outside the target regions, due to the target enrichment. We
      also compared genotype concordance for variant calls obtained by exome sequencing
      vs. exome genotyping microarrays. The overall consistency rate was >99.83% and
      the heterozygous consistency rate was >97.55%. The two platforms share a large
      amount of agreement over low frequency variants in the exonic regions, while
      exome sequencing provides much more information on variants not included on exome
      genotyping microarrays. The results demonstrate that exome sequencing data are of
      high quality and can be used to investigate the role of rare coding variants in
      human diseases. 

PMID- 24032040
TI  - The Clinical Significance of Serum Apoptotic Cytokeratin 18 Neoepitope M30 (CK-18
      M30) and Matrix Metalloproteinase 2 (MMP-2) Levels in Chronic Hepatitis B
      Patients with Cirrhosis.
AB  - BACKGROUND: Serum apoptotic cytokeratine 18 neoepitope M30 (CK-18 M30) and matrix
      metalloproteinase 2 (MMP-2) have been popular markers for detecting liver
      fibrosis in recent years. CK-18 is a major intermediate filament protein in liver
      cells and one of the most prominent substrates of caspases during hepatocyte
      apoptosis. MMP-2 plays an important role in tissue remodeling and repairing
      processes during physiological and pathological states. OBJECTIVES: The objective
      of this study was to investigate the significance of CK-18 M30 and MMP-2 levels
      for clinical use in patients with chronic hepatitis B (CHB), as well as their
      sensitivity in determining cirrhotic patients. PATIENTS AND METHODS: This study
      included 189 CHB patients and 51 healthy controls. A modified Knodell scoring
      system was used to determine the fibrosis level in chronic hepatitis B patients.
      CK-18 M30 levels were determined with an M30-Apoptosense ELISA assay. MMP-2
      levels were determined with the ELISA assay. RESULTS: The study group consisted
      of 132 (69.8%) males and 57 (30.2%) females, and the control group consisted of
      25 males (49.0%) and 26 females (51%). Patients' CK-18 M30 levels were higher
      than values of the control group (308 [1-762] vs. 168 [67-287], P=0.001). Serum
      MMP-2 levels were found to be statistically higher in the patient group with
      respect to the controls (3.0 [1.1-6.8] vs. 2.0 [1.2-3.4], P=0.001). The highest
      serum CK-18 M30 and MMP-2 levels were measured in patients with cirrhosis. Serum
      apoptotic CK-18 M30 levels positively correlated with advanced age, fibrosis
      stage, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      levels (P= 0.001, 0.033, 0.001, and 0.001, respectively). Serum MMP-2 levels
      positively correlated with fibrosis stage, serum ALT, and AST levels (P= 0.001,
      0.001, and 0.001, respectively). CONCLUSIONS: Our study indicated that CK-18 M30
      and MMP-2 levels were higher in CHB patients compared to healthy controls and
      they were in association with significant hepatic fibrosis, especially cirrhosis.

PMID- 24032041
TI  - Recurrent Hepatitis in Two Iranian Children: A Novel (Q166R) Mutation in EIF2AK3
      Leading to Wolcott-Rallison Syndrome.
AB  - Early-onset diabetes, liver dysfunction, growth retardation, spondyloepiphyseal
      dysplasia, and tendency to skeletal fractures due to osteopenia are
      characteristics of Wolcott-Rallison syndrome (WRS). Eukaryotic translation
      initiation factor 2alpha kinase (EIF2AK3) is the only known gene, which is
      responsible for this rare autosomal recessive disorder. Here, we report two
      siblings a girl and a boy with diabetes mellitus (DM) who presented in one and
      two months of age respectively. Recurrent self-limiting hepatitis developed
      later, and severe hepatic failure resulted in death of the first child. The
      second child visited was a 7.75 year old boy who had spondyloepiphyseal dysplasia
      and subclinical hypothyroidism besides DM and recurrent hepatitis. We suggested
      WRS for this patient, and it was confirmed by identification of a novel
      homozygous missense mutation (Q166R) in exon 3 of the EIF2AK3 gene. The aim of
      this report is to remind the possibility of WRS in isolated neonatal diabetes;
      while, the other clinical manifestations of this syndrome including its major
      symptom of recurrent hepatitis may appear later. 

PMID- 24032042
TI  - Effect of Functional Interleukin-10 Polymorphism on Pegylated Interferon-alpha
      Plus Ribavirin Therapy Response in Chronic Hepatitis C Virus Patients Infected
      With 3a Genotype in Pakistani Population.

PMID- 24032043
TI  - Adherence to chronic hepatitis C treatment regimen: first report from a referral
      center in iran.
AB  - BACKGROUND: Various aspects of adherence to HCV treatment such as frequency, risk
      factors as well as causes of non-adherence, and its real role in clinical and
      virological outcome of the infected patients have remained largely unknown.
      OBJECTIVES: The current study aimed to evaluate patients' adherence to anti-HCV
      medications in Iran. MATERIALS AND METHODS: From October 2010 to March 2011,
      socio-demographic characteristics, features of HCV infection, clinical
      properties, and habitual history of 190 patients were collected. Adherence of
      each patient to anti-HCV medications was determined at months 1, 3, and 6 of
      treatment by self-reporting and pill or empty ampoule counting. Adherence to anti
      HCV treatment regimen was determined based on the 80/80/80 rule. RESULTS:
      Adherence rate to interferon, ribavirin, or a combination of them over the first
      6 months of therapy in Iranian HCV patients measured by both methods of self
      reporting and pill counting were 35.4-65.8%, 46.3-56.8%, and 28.4-51.1%,
      respectively. Delay in receiving new prescription, financial issues, and adverse
      drug reactions were the most common causes of non-adherence in the patients.
      Adherence to ribavirin was identified as an independent predictor of achieving
      the end of treatment response, or sustained virological response. CONCLUSIONS:
      The rate of adherence to interferon and ribavirin varied significantly according
      to the method of calculation. Over the treatment course, adherence to interferon
      alpha and ribavirin, each or their combination, diminished significantly.

PMID- 24032044
TI  - Assessment of viral genotype impact to the cost-effectiveness and overall costs
      of care for PEG-interferon-2alpha + ribavirine treated chronic hepatitis C
      patients.
AB  - BACKGROUND: Pegylated interferon alfa plus ribavirin protocol is currently
      considered the most efficient hepatitis C treatment. However, no evidence of
      costs comparison among common viral genotypes has been published. OBJECTIVES: We
      aimed to assess core drivers of hepatitis C medical care costs and compare cost
      effectiveness of this treatment among patients infected by hepatitis C virus with
      genotypes 1 or 4 (group I), and 2 or 3 (group II). PATIENTS AND MATERIALS:
      Prospective bottom-up cost-effectiveness analysis from societal perspective was
      conducted at Infectious Diseases Clinic, University Clinic Kragujevac, Serbia,
      from 2007 to 2010. There were 81 participants with hepatitis C infection, treated
      with peg alpha-2a interferon plus ribavirin for 48 or 24 weeks. Economic data
      acquired were direct inpatient medical costs, outpatient drug acquisition costs,
      and indirect costs calculated through human capital approach. RESULTS: Total
      costs were significantly higher (P = 0.035) in group I (mean +/- SD: 12,751.54 +/
      5,588.06) compared to group II (mean +/- SD: 10,580.57 +/- 3,973.02). In
      addition, both direct (P = 0.039) and indirect (P < 0.001) costs separately were
      significantly higher in group I compared to group II. Separate comparison within
      direct costs revealed higher total cost of medical care (P = 0.024) in first
      compared to second genotype group, while the similar tendency was observed for
      total drug acquisition (P = 0.072). CONCLUSION: HCV genotypes 1 and 4 cause more
      severe clinical course require more care and thus incur higher expenses compared
      to HCV 2 and 3 genotypes. Policy makers should consider willingness to pay
      threshold differentially depending upon HCV viral genotype detected.

PMID- 24032045
TI  - Efficacy and Safety of Telbivudine Compared to Entecavir Among HBeAg+ Chronic
      Hepatitis B Patients: a Meta-Analysis Study.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a serious global health problem
      that is associated with huge social and economic costs. Early antiviral drugs,
      such as interferon-alpha2b, peginterferon-alpha2a, lamivudine, and adefovir, all
      have their limitations (such as low responses or safety concerns) in clinical
      application. Telbivudine and entecavir are two of the latest nucleotide drugs and
      both have been shown to have potent viral suppression. However, in patients with
      hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB), inconsistent
      results have been generated for efficacy between telbivudine and entecavir.
      Therefore, evidence-based medical data are required to compare the efficacies, in
      terms of virological and biochemical responses, and safety between telbivudine
      and entecavir. OBJECTIVES: We aimed to compare the early antiviral efficacy and
      safety of telbivudine and entecavir in the treatment of patients with hepatitis B
      e antigen (HBeAg)-positive chronic hepatitis B (CHB). PATIENTS AND METHODS: A
      search for relevant randomized controlled trials (RCTs) on HBeAg-positive CHB
      patients treated with telbivudine and entecavir for 24 or 52 weeks, published
      before December 2011, was performed. Primary efficacy endpoint was the cumulative
      rate of undetectable HBV DNA, and secondary efficacy endpoints included rates of
      alanine aminotransferase (ALT) normalization, HBeAg disappearance, HBeAg
      seroconversion and adverse events. Meta-analysis was performed using the Review
      Manager v5.1.4 software package. We assessed the pooled risk ratios (RRs) and 95%
      confidence intervals (CIs) using the fixed-or random-effects model. RESULTS: Six
      randomized controlled trials (RCTs) involving 555 patients were included.
      Telbivudine was associated with significantly higher rates of HBeAg disappearance
      (RR = 1.46, 95% CI: 1.11 - 1.91) and HBeAg seroconversion (RR = 1.76, 95%CI: 1.25
      2.48) than entecavir, but had higher adverse events (RR = 2.11, 95%CI: 1.23 -
      3.60), compared with entecavir. There was no difference between telbivudine and
      entecavir in the rate of cumulative undetectable HBV DNA (RR = 0.99, 95% CI: 0.90
      - 1.10) and ALT normalization (RR = 0.93, 95% CI: 0.85 - 1.00). CONCLUSIONS:
      Telbivudine is associated with significantly higher rates of HBeAg disappearance
      and HBeAg seroconversion than entecavir, whereas entecavir is superior to
      telbivudine in safety. Both drugs have similar efficacy on rates of cumulative
      undetectable HBV DNA and ALT normalization.

PMID- 24032046
TI  - Recombinant Nonstructural 3 Protein, rNS3, of Hepatitis C Virus Along With
      Recombinant GP96 Induce IL-12, TNFalpha and alpha5integrin Expression in Antigen
      Presenting Cells.
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is the main cause of chronic liver
      disease and to date there has been no vaccine development to prevent this
      infection. Among non-structural HCV proteins, NS3 protein is an excellent goal
      for a therapeutic vaccine, due to its large size and less variation in conserved
      regions. The immunogenic properties of heat shock proteins (HSPs) for instance
      GP96 have prompted investigations into their function as strong adjuvant to
      improve innate and adaptive immunity. OBJECTIVES: The aim of this study was to
      examine additive effects of recombinant GP96 (rGP96) fragments accompanied by
      rNS3 on expression levels of alpha5integrin and pro-inflammatory cytokines, IL-12
      and TNFalpha, in Antigen Presenting Cells (APCs). MATERIALS AND METHODS:
      Recombinant viral proteins (rNS3 and rRGD-NS3), N-terminal and C-terminal
      fragments of GP96 were produced and purified from E. coli in order to treat the
      cells; mouse spleen Dendritic Cells (DCs) and THP-1 macrophages. RESULTS: Our
      results showed that rNT-GP96 alone significantly increases the expression level
      of IL-12, TNFalpha and alpha5integrin in THP-1 macrophages and DCs, while IL-12
      and TNFalpha expression levels were unaffected by either rNS3 or rRGD-NS3.
      Interestingly, the co-addition of these recombinant proteins with rNT-GP96
      increased IL-12, TNFalpha and alpha5integrin expression. Pearson Correlation
      showed a direct association between alpha5integrin with IL-12 and TNF-alpha
      expression. CONCLUSIONS: we have highlighted the role of rNS3 plus rNT-GP96
      mediated by alpha5integrin in producing IL-12 and TNFalpha. It can be suggested
      that rNT-GP96 could enhance immunity characteristic of rNS3 protein via
      production of pro-inflammatory cytokines.

PMID- 24032047
TI  - The effects of Leptin and Adiponectin on Pdx1, Foxm1, and PPARgamma Transcription
      in Rat Islets of Langerhans.
AB  - BACKGROUND: Leptin and adiponectin are two hormones, which are released from
      adipocytes in order to control energy expenditure. Both hormones are also
      involved in glucose homeostasis through control of insulin secretion from
      pancreatic islets. Since Pdx1, PPARgamma, and foxm1 play important roles in
      islets function, it is essential to understand how these genes are regulated in
      the islets of Langerhans. OBJECTIVES: We have designed an experiment to identify
      the effect of leptin and adiponectin treatment on Pdx1, PPARgamma, and foxm1
      transcription. MATERIALS AND METHODS: Islets were isolated from adult male rats
      by collagenase and incubated with different concentrations of leptin and
      adiponectin for 24 hours. Next, by means of real time PCR, we evaluated the gene
      transcription related to a housekeeping gene. The effect of leptin and
      adiponectin on insulin secretion was evaluated by ELISA. RESULTS: Leptin
      decreased PPARgamma transcription and insulin secretion, while adiponectin
      significantly increased Pdx1 and PPARgamma transcription and insulin secretion in
      rat islets. The transcription of foxm1 did not change in the islet cells treated
      with leptin or adiponectin. CONCLUSIONS: These findings indicate the possibility
      that Pdx1 and PPARgamma transcription is a mediator of leptin and adiponectin
      function in control of insulin secretion and glucose homeostasis in pancreatic
      islets.

PMID- 24032048
TI  - Hepatitis C virus (HCV) Infection Rate among Seronegative Hemodialysis Patients
      Screened by Two Methods; HCV Core Antigen and Polymerase Chain Reaction.
AB  - BACKGROUND: End-stage renal disease patients on chronic hemodialysis are among
      high risk groups for hepatitis C virus (HCV) infection for whom routine HCV
      screening is recommended. Anti-HCV antibody (ab) testing may not be reliable to
      detect all infected cases because of the blunted ab response due to depressed
      immune state in these patients. Using a more reliable, cost-effective and non
      complex HCV screening test may be necessary in this group of patients for case
      finding and management, and also for prevention of infection spread. OBJECTIVES:
      The aim of this study was to find the prevalence of HCV infection in HCV ab
      negative hemodialysis patients by Real time PCR and total HCV core antigen (ag)
      test and comparing the results of the two tests. PATIENTS AND METHODS: From a
      single hemodialysis center, 181 anti- HCV ab negative patients were screened by
      total HCV core ag using an ELISA kit. Real time PCR was used for determination of
      the virus and viral load quantity. RESULTS: Among the 181 anti-HCV ab negative
      patients, 13 (7.2%) were positive for HCV core ag and 11 (6%) had detectable HCV
      RNA with a range of 40-336543 IU/ml by PCR. The two tests had a high measurement
      agreement (Kappa=0.82, P<0.001). Of the 13 patients with positive HCV core ag
      test results, 3 were negative for HCV RNA. Considering real time PCR for HCV RNA
      as the gold standard for HCV infection determination in this patient population,
      HCV core ag assay yielded a sensitivity of 90.9%, specificity of 98.2%, positive
      predictive value of 76.9% and negative predictive value of 99.4%. DISCUSSION: The
      rate of HCV infection among HCV ab negative hemodialysis patients was high. HCV
      core ag testing could be used as a sensitive method for HCV infection screening
      in this group of patients.

PMID- 24032049
TI  - Histopathology of post-transplant liver biopsies, the first report from iran.
AB  - BACKGROUND: Evaluation of a transplanted liver by Imaging techniques and enzyme
      changes is sensitive to hepatocellular or biliary problems, but in most instances
      liver allograft biopsies are performed in order to find out the final reason for
      these changes. OBJECTIVES: It's been about 17 years (with more than 1326 cases)
      since the first liver transplantation in the Namazi Hospital of Shiraz University
      of Medical Sciences while during the last five years the number of post liver
      transplant biopsies have increased. Until now there has been no report of the
      pathological results of post liver transplant needle biopsies from Iran.
      MATERIALS AND METHODS: During the last 5 years, there have been 382 post liver
      transplant biopsies. We studied the clinical charts and pathological results of
      all needle biopsies. RESULTS: A total of 382 needle biopsies were performed on
      287 patients aged between 1 and 64 years old. The earliest specimen was obtained
      within the first few hours following transplantation, and the last was gathered
      3209 days (261 +/- 523) post-transplantation. Acute rejection was the most common
      diagnosis, which occurred in 180 (47%) of specimens. Among other complications
      were vascular problems (8.6%), preservation/reperfusion (I/R) injury (7%),
      chronic rejection (5.2%), biliary injury/obstruction (3.4%), recurrence of
      primary disease (2.6%), drug-induced hepatic injury (1.8%), cirrhosis (1.6%),
      sepsis (1.4%), cytomegalovirus hepatitis (1.4%), post-transplantation
      lymphoproliferative disease (1%) and Venous outflow obstruction (0.5%).
      CONCLUSIONS: The most common pathological diagnosis of post-transplant liver
      needle biopsies has been acute rejection, followed by ischemia due to hepatic
      artery thrombosis, preservation/reperfusion injury, and chronic rejection.

PMID- 24032050
TI  - Health related quality of life in Iranian hemodialysis patients with viral
      hepatitis: changing epidemiology.
AB  - BACKGROUND: There are surprisingly a few studies that evaluate the impact of
      chronic viral hepatitis, which is common in HD (hemodialysis) patients, on HRQOL
      (health related quality of life). OBJECTIVES: We conducted a study to evaluate
      the impact of chronic viral hepatitis on HRQOL and to compare their HRQOL with
      non-infected HD patients via a HRQOL questionnaire. PATIENTS AND METHODS: The
      Iranian adapted version of the Kidney Disease Quality of Life Short Form (KDQOL
      SF) version 1.3 questionnaires were filled out by the HD patients. In all HD
      patients, serum HBsAg, HBS Abs, and HCV Abs [enzyme-linked immunosorbant assay
      (ELISA)] were routinely checked every six months. Patients were considered to
      have chronic HBV infection if HBsAg was positive for more than six months. In all
      HD patients, third generation assay was used to detect HCV infection.
      Furthermore, serum HCV-RNA (PCR) was examined in anti-HCV-positive patients for
      confirmation of HCV infection. RESULTS: in this cross sectional study 4101
      patients from 103 dialysis units in Iran between October 2010 and August 2011
      were included. Prevalence of hepatitis B and hepatitis C infection was 2.1% and
      1.3% respectively. Almost all KDQOL items for viral hepatitis patients had
      equivalent or better scores than those without viral hepatitis. In the logistic
      regression after adjustment for age, sex, educational level, marital status,
      dialysis vintage, HBs Ag positivity and HCV Ab positivity, only age (P < 0.001)
      and educational level (P = 0.015) had negative impact on quality of life.
      CONCLUSIONS: Our data show that not only general health and physical activity
      were preserved but also health perception may be better among HD patients with
      viral hepatitis.

PMID- 24032051
TI  - The Biological Residue of Childhood Poverty.
AB  - Children raised in poverty are prone to physical health problems late in life. To
      understand these findings and address the scientific challenge they represent, we
      must formulate integrative conceptual frameworks at the crossroads of behavioral
      and biomedical science, with a strong developmental emphasis. In this article, we
      outline such a framework and discuss research bearing on its validity. We address
      how childhood poverty gets under the skin, at the level of tissues and organs, in
      a manner that affects later disease risks. We also tackle questions about
      resilience; Even with lengthy exposure to childhood poverty, why do only a subset
      of people acquire diseases? Why are some individuals protected while others
      remain vulnerable? Maternal nurturance might be a source of resilience, buffering
      children from the long-term health consequences of poverty. We conclude with
      research priorities.

PMID- 24032052
TI  - Tobacco advertising and press coverage of smoking and health in 10 years of
      Argentinean newspapers.
AB  - OBJECTIVE: To describe the extent and content of tobacco-related images,
      advertising and articles published in the largest Argentinean newspapers before
      and after a voluntary advertising ban implemented in 2001. METHODS: Issues from
      four months of each year of the four main national newspapers were examined from
      1995 to 2004. We recorded the number of tobacco images (advertisement or not),
      tobacco-focused articles, space used, and placement within the newspaper.
      Regression analyses evaluated time trends. RESULTS: We identified 1800 images and
      articles from 4828 different issues. Non-advertisement images were the most
      frequent (71.2%), followed by articles (20%) and advertisement images (8.8%).
      Advertisements only appeared in the two best selling newspapers with a majority
      (57%) in the Sunday magazine and 21% in the sports sections. Non-advertisement
      images were published in the sports and entertainment sections (55%) and showed a
      public figure in 88%. Of 336 articles, 39% focused on health topics and 55%
      emphasized the negative effects of tobacco on health. Regression models showed
      that prior to 2001 there were significant time-related decreases in ad images and
      articles and significant increases in non-ad images. The trend of each outcome
      changed direction beginning in 2001 and the magnitude of the change in trend was
      significant for ad images and non-ad images. The number of non-ad images dropped
      significantly in 2001 from a model-predicted value of 178 per year to 103 non-ad
      images and remained constant thereafter. CONCLUSIONS: Tobacco images exceeded
      information about tobacco hazards in Argentinean newspapers over this period.
      Advertisement increased from 2001 to 2005, following the voluntary advertisements
      ban. Partial advertisement bans are ineffective and a total ban is imperative.

PMID- 24032054
TI  - The editorial process: Peer review.

PMID- 24032055
TI  - To volunteer is to live longer.

PMID- 24032056
TI  - CUA-CUOG guidelines for the management of castration-resistant prostate cancer
      (CRPC): 2013 update.

PMID- 24032057
TI  - Management of advanced kidney cancer: Canadian Kidney Cancer Forum 2013 Consensus
      Update: Canadian Kidney Cancer Forum 2013.

PMID- 24032058
TI  - Improved wait time intervals for prostate cancer patients in a multidisciplinary
      rapid diagnostic unit compared to a community-based referral pattern.
AB  - BACKGROUND: Wait times in cancer diagnosis and treatment may significantly affect
      a patient's treatment outcome, prognosis and quality of life. The purpose of this
      study was to capture wait time intervals for patients with prostate cancer
      treated with radiotherapy (RT) at the Odette Cancer Centre, Toronto, Ontario,
      Canada and to compare patients diagnosed in a rapid diagnostic unit (RDU) versus
      the usual community referral process. METHODS: Patients agreed to participate in
      the study during their RT planning sessions. A semi-structured interview and
      chart abstraction was conducted to record key wait time milestones. RESULTS: A
      total of 87 patients participated in the study: 44 RDU patients and 43 community
      patients. The median overall wait time intervals from suspicion of prostate
      cancer to RT was 138 and 183 days, respectively (p = 0.046). There were
      statistically significant differences observed for other key wait time intervals
      favouring the RDU cohort: suspicion to decision-to-treat (DTT; p = 0.012),
      urologist visit to diagnosis (p = 0.0094), diagnosis to DTT (p = 0.018), and
      diagnosis to treatment (p = 0.016). Risk category and Gleason sum was
      independently predictive of longer intervals from diagnosis to DTT.
      INTERPRETATION: Wait time intervals from suspicion to treatment are significantly
      shorter for prostate cancer patients in 2011 to 2012 than in 2003 when patients
      were diagnosed and referred in the community setting. A prostate-specific RDU
      further reduced a number of key wait time intervals supporting more
      multidisciplinary RDUs for common diseases. Further work needs to be done to
      identify why delays are occurring and to develop new processes to minimize
      delays.

PMID- 24032059
TI  - Is faster enough? Wait time intervals in prostate cancer treatment.

PMID- 24032060
TI  - Sexual function outcomes following fracture of the penis.
AB  - INTRODUCTION: Fracture of the penis is a rare urological emergency which occurs
      as a result of abrupt trauma to an erect penis. There is paucity of data
      regarding long-term sexual function or erectile potency following fracture of the
      penis. The aim of this study is to objectively assess the overall sexual function
      following fracture of the penis. METHODS: A retrospective analysis of 21 penile
      fractures was performed. A voluntary telephone questionnaire was performed to
      assess long term outcomes using three validated questionnaires-the Erection
      Hardness Grading Scale, the International Index of Erectile Function (IIEF-5) and
      the Brief Male Sexual Function inventory (BMSFI). RESULTS: The mean age was 33.1
      years (range: 19-63). The median follow up was 46 months (range: 3-144). All
      fractures were a result of sexual misadventure and all were surgically repaired.
      There were two concomitant urethral injuries. Seventeen patients were
      contactable. Fourteen patients demonstrated no evidence of erectile dysfunction
      (ED) (IIEF-5>22), 1 patient reported symptoms of mild ED (IIEF-5, 17-21) and one
      patient reported mild to moderate ED (IIEF-5, 12-16). No patients reported
      insufficient erection for penetration (EHGS: 1 or 2). Regarding the overall
      BMSFI, 13 (83%) patients were mostly satisfied or very satisfied with their sex
      life within the previous month. CONCLUSION: In a small surgical series of men
      with penile fracture managed within a short time frame from presentation, we
      demonstrate erectile potency is maintained. Long-term overall sexual satisfaction
      is promising.

PMID- 24032061
TI  - Addressing the barriers to optimal management of penile fracture.

PMID- 24032062
TI  - Are physicians performing neonatal circumcisions well-trained?
AB  - INTRODUCTION: Notwithstanding the recommendations from the Canadian Pediatric
      Association and the American Academy of Pediatrics on the indications for
      neonatal circumcision, this procedure is still common in North America and
      throughout the world. Our purpose is not to argue whether this procedure should
      be done, but rather to examine who is doing it, their training, how it is
      performed and how can we prevent unsatisfactory results and complications. The
      objective is to identify what fields of knowledge require improvement and then
      design a teaching module to improve the outcomes of neonatal circumcision.
      METHODS: A 19-question cross-sectional survey, including a visual identification
      item, was submitted to 87 physicians who perform neonatal circumcisions in
      Southwestern Ontario, Canada. To improve our response rate, study subjects were
      contacted in a variety of ways, including mail and fax and telephone. Once the
      survey was completed, we produced a surgical technique training video on using
      the Gomco clamp and the Plastibell techiques. A knowledge dissemination workshop
      was held with survey participants to discuss contraindications and the use of
      anesthesia and management of complications of neonatal circumcision and to
      evaluate the surgical technique training video. A 6-month follow-up questionnaire
      was completed to determine the impact of the teaching course on participants'
      daily practice. RESULTS: In total, we received 54 responses (62% response rate).
      From these, 46 (85%) were family doctors and pediatricians, while the remaining 8
      (15%) were pediatric general surgeons and urologists. The circumcisions were
      carried out with the Gomco clamp 35 (63%) and the Plastibell 21 (37%). No
      respondent admitted to learning the procedure through a structured training
      course. Of the non-surgeons, 19 (43%) learned to perform a circumcision from a
      non-surgeon colleague. A little over a third of the participants (17, 31%) were
      happy to perform a circumcision in a child born with a concealed penis, where
      circumcision is contraindicated. With respect to the early complications post
      circumcision, 8 (100%) surgeons versus 29 (63%) non-surgeons felt comfortable
      dealing with bleeding (p = 0.046). In total, 7 (88%) surgeons versus 16 (35%) non
      surgeons were comfortable dealing with urinary retention (p = 0.01). Also, 8
      (100%) surgeons versus 24 (52%) non-surgeons were comfortable dealing with a
      wound dehiscence (p = 0.02). Moreover, 6 (75%) surgeons and 5 (10%) non-surgeons
      were comfortable managing meatal stenosis (p < 0.01). Five (63%) surgeons versus
      15 (33%) non-surgeons were confident in dealing with a trapped penis post
      circumcision (p = 0.24). CONCLUSIONS: Our survey findings indicate that most
      physicians performing neonatal circumcisions in our community have received
      informal and unstructured training. This lack of formal instruction may explain
      the complications and unsatisfactory results witnessed in our pediatric urology
      practice. Many practitioners are not aware of the contraindications to neonatal
      circumcision and most non-surgeons perform the procedure without being able to
      handle common post-surgical complications. Based on our survey findings, we
      planned and carried out a formal training course to address these issues.

PMID- 24032063
TI  - Teaching neonatal circumcision.

PMID- 24032064
TI  - The effectiveness of continuing medical education for specialist recertification.
AB  - Evolving professional, social and political pressures highlight the importance of
      lifelong learning for clinicians. Continuing medical education (CME) facilitates
      lifelong learning and is a fundamental factor in the maintenance of
      certification. The type of CME differs between surgical and non-surgical
      specialties. CME methods of teaching include lectures, workshops, conferences and
      simulation training. Interventions involving several modalities, instructional
      techniques and multiple exposures are more effective. The beneficial effects of
      CME can be maintained in the long term and can improve clinical outcome. However,
      quantitative evidence on validity, reliability, efficacy and cost-effectiveness
      of various methods is lacking. This is especially evident in urology. The
      effectiveness of CME interventions on maintenance of certification is also
      unknown. Currently, many specialists fulfil mandatory CME credit requirements
      opportunistically, therefore erroneously equating number of hours accumulated
      with competence. New CME interventions must emphasize actual performance and
      should correlate with clinical outcomes. Improved CME practice must in turn lead
      to continuing critical reflection, practice modification and implementation with
      a focus towards excellent patient care. 

PMID- 24032065
TI  - Assessment of antibiotic prophylaxis prescribing patterns for TURP: A need for
      Canadian guidelines?
AB  - BACKGROUND: While antibiotic prophylaxis is recommended to all patients
      undergoing transurethral resection of prostate (TURP), little data exist
      regarding prescribing patterns of urologists prior to this procedure. Here, we
      sought to determine real-world antibiotic prophylaxis prescribing patterns at a
      high volume Canadian institution and determine compliance rates to
      recommendations put forth by the American Urological Association's (AUA) Best
      Practice Statement (BPS) on antimicrobial prophylaxis. METHODS: A retrospective
      chart review of 488 patients undergoing TURP was conducted. Electronic medical
      records were reviewed to determine antibiotics prescribed 3 hours preoperatively
      and 24 hours postoperatively. For patients without a catheter, compliance was
      defined as those receiving an antibiotic prior to TURP. In patients with an
      indwelling catheter, compliance was defined as those receiving antibiotics from
      two different classes prior to surgery. RESULTS: Overall, a total of 30
      antibiotic regimens were utilized. The most common single antibiotic regimens
      prescribed were ciprofloxacin (32%), cefazolin (25%) and gentamicin (3%). In
      those patients with indwelling Foley catheters prior to TURP, a significant
      increase in gentamicin, as well as combination antibiotic regimens, was noted.
      The compliance rate with the AUA BPS in patients without a preoperative catheter
      was 81%, while the compliance rate for patients with an indwelling catheter prior
      to TURP was 37%. INTERPRETATION: Collectively, our results demonstrate that
      prescribing patterns vary significantly prior to TURP, with compliance to AUA BPS
      being lower than anticipated. Overall, these results support educational efforts
      in this area, and the development of Canadian recommendations to improve uptake
      by practicing urologists.

PMID- 24032066
TI  - Canada's first robotic-assisted totally intracorporeal orthotopic ileal
      neobladder.
AB  - Despite robotic-assisted radical cysto-prostatectomy being performed in several
      centres, the urinary diversion is most often performed extra-corporeal. A robotic
      intra-corporeal ileal neobladder is technically demanding and long-term
      functional outcome data is lacking. We performed a robotic intra-corporeal ileal
      neobladder in a 73-year-old man for muscle invasive non-metastatic bladder
      cancer. The total operative time was 6 hours 8 minutes. The estimated blood loss
      was 900 mL. There were no complications and he was discharged on day 12. The
      principles of open neobladder surgery were maintained, however key modifications
      were used to reduce technical difficulty and enable timely completion. We found
      that robotic intracorporeal ileal neobladder can be safely performed with an
      experienced robotic unit. 

PMID- 24032067
TI  - Antibiotic use prior to transurethral resection of the prostate: Are we doing
      what we think we are doing?

PMID- 24032068
TI  - Metastatic prostate cancer in transsexual diagnosed after three decades of
      estrogen therapy.
AB  - The incidence of prostate cancer in transsexual patients is very low with only
      few reported cases. Many years before presenting with prostate cancer, these
      patients receive hormone ablation as a part of their gender therapy. Their
      disease is already defined as castrate resistant, and the treatment and follow-up
      of such patients remains a challenge. We report a case of a male-to-female
      transgender woman who was diagnosed with metastatic prostate cancer, 31 years
      post-feminization. 

PMID- 24032069
TI  - Flank bulge following supracostal percutaneous nephrolithotomy: A report of 2
      cases.
AB  - Damage to intercostal nerves during surgical procedures has been associated with
      a postoperative flank bulge, due to denervation of the anterolateral abdominal
      wall musculature. This complication has not been reported following percutaneous
      nephrolithotomy (PCNL). We are aware of 3 cases, but have details on 2 cases of
      postoperative flank bulge following supracostal PCNL which are reported here. We
      also suggest how this complication could potentially be minimized. 

PMID- 24032070
TI  - Hierarchical self-assembly of actin in micro-confinements using microfluidics.
AB  - We present a straightforward microfluidics system to achieve step-by-step
      reaction sequences in a diffusion-controlled manner in quasi two-dimensional
      micro-confinements. We demonstrate the hierarchical self-organization of actin
      (actin monomers-entangled networks of filaments-networks of bundles) in a
      reversible fashion by tuning the [Formula: see text] ion concentration in the
      system. We show that actin can form networks of bundles in the presence of
      [Formula: see text] without any cross-linking proteins. The properties of these
      networks are influenced by the confinement geometry. In square microchambers we
      predominantly find rectangular networks, whereas triangular meshes are
      predominantly found in circular chambers. 

PMID- 24032071
TI  - Public Policies, Women's Employment after Childbearing, and Child Well-Being.

PMID- 24032072
TI  - When Feeling Bad Can Be Good: Mixed Emotions Benefit Physical Health Across
      Adulthood.
AB  - Traditional models of emotion-health interactions have emphasized the deleterious
      effects of negative emotions on physical health. More recently, researchers have
      turned to potential benefits of positive emotions on physical health as well.
      Both lines of research, though, neglect the complex interplay between positive
      and negative emotions and how this interplay affects physical well-being. Indeed,
      recent theoretical work suggests that a strategy of "taking the good with the
      bad" may benefit health outcomes. In the present study, the authors assessed the
      impact of mixed emotional experiences on health outcomes in a 10-year
      longitudinal experience-sampling study across the adult life span. The authors
      found that not only were frequent experiences of mixed emotions (co-occurrences
      of positive and negative emotions) strongly associated with relatively good
      physical health, but that increases of mixed emotions over many years attenuated
      typical age-related health declines.

PMID- 24032073
TI  - Free Base Lysine Increases Survival and Reduces Metastasis in Prostate Cancer
      Model.
AB  - BACKGROUND: Malignant tumor cells typically metabolize glucose anaerobically to
      lactic acid even under normal oxygen tension, a phenomenon called aerobic
      glycolysis or the Warburg effect. This results in increased acid production and
      the acidification of the extracellular microenvironment in solid tumors. H+ ions
      tend to flow along concentration gradients into peritumoral normal tissue causing
      extracellular matrix degradation and increased tumor cell motility thus promoting
      invasion and metastasis. We have shown that reducing this acidity with sodium
      bicarbonate buffer decreases the metastatic fitness of circulating tumor cells in
      prostate cancer and other cancer models. Mathematical models of the tumor-host
      dynamics predicted that buffers with a pka around 7 will be more effective in
      reducing intra- and peri-tumoral acidosis and, thus, and possibly more effective
      in inhibiting tumor metastasis than sodium bicarbonate which has a pKa around 6.
      Here we test this prediction the efficacy of free base lysine; a non
      bicarbonate/non-volatile buffer with a higher pKa (~10), on prostate tumor
      metastases model. METHODS: Oxygen consumption and acid production rate of PC3M
      prostate cancer cells and normal prostate cells were determined using the
      Seahorse Extracellular Flux (XF-96) analyzer. In vivo effect of 200 mM lysine
      started four days prior to inoculation on inhibition of metastasis was examined
      in PC3M-LUC-C6 prostate cancer model using SCID mice. Metastases were followed by
      bioluminescence imaging. RESULTS: PC3M prostate cancer cells are highly acidic in
      comparison to a normal prostate cell line indicating that reduction of intra- and
      perit-tumoral acidosis should inhibit metastases formation. In vivo
      administration of 200 mM free base lysine increased survival and reduced
      metastasis. CONCLUSION: PC3M prostate cancer cells are highly glycolytic and
      produce large amounts of acid when compared to normal prostate cells.
      Administration of non-volatile buffer decreased growth of metastases and improved
      survival indicating acidity plays a significant role in growth and invasion in
      vivo.

PMID- 24032074
TI  - Supramolecular Assembly of DNA on Graphene Nanoribbons.
AB  - Graphene's adhesive and charge delocalization properties offer the opportunity
      for the direct study of biological molecule in the nanoscale regime. The inherent
      charge on DNA base pairs and the associated phosphate backbone can be probed by
      non-covalent interactions with graphene, which is a useful platform for the
      creation of anisotropic nanopatterned biological assemblies. Here, we report the
      graphene nanoribbon (GNR) supported anisotropic supramolecular self-assembly of
      single stranded adenine (A), cytosine (C), guanine (G), thymine (T), AT, and GC
      20mer oligonucleotides, as well as the unique ordering of double stranded plasmid
      (circular) and Herring sperm (linear) DNA. The GNRs serve as a double sided
      adhesive platform for attachment to the SiO2 substrate, as well as DNA oligomers
      and polymers. The self-assembly is attributed to donor-acceptor interactions
      between DNA and graphene. These findings demonstrate that the DNA-GNR assembly
      yields a prospective route to novel bio-relevant nanostructures.

PMID- 24032076
TI  - Sonographic localization of a nonpalpable shunt: Ultrasound-assisted ventricular
      shunt tap.
AB  - BACKGROUND: Patients frequently present to the emergency department (ED) for
      evaluation of cerebrospinal fluid (CSF) shunt malfunction, often requiring urgent
      management. A typical evaluation in the emergency room setting includes a
      thorough history and physical examination, noncontrasted head computed tomography
      (CT), shunt series, and occasionally a ventricular shunt tap. CASE DESCRIPTION:
      We present the case of a 53-year-old male who initially presented to the ED in
      acute status epilepticus. His history was notable for seizures and multiple
      craniectomies and cranioplasties with subsequent placement of a
      ventriculoperitoneal shunt secondary to traumatic brain injury. Imaging in the ED
      suggested possible shunt failure. No previous imaging was available for
      comparison, and therefore a ventricular shunt tap was attempted. Initially, the
      tap could not be performed, as the shunt was not palpable secondary to the
      thickness of his scalp and location of the reservoir near his complex cranial
      reconstruction site. We report, for the first time, the utility of emergency
      ultrasound (EUS) to aid in such an encounter. CONCLUSION: EUS revealed the exact
      location of his shunt reservoir, and therefore enabled the shunt tap, which
      ultimately led to the discovery of the patient's proximal shunt failure in a
      setting that may have otherwise been missed. The patient underwent urgent shunt
      revision with a good outcome.

PMID- 24032077
TI  - Is "en-bloc" excision, an option for select large vascular meningiomas?
AB  - BACKGROUND: Large highly vascular meningiomas surgically challenging when
      preoperative embolization is not feasible. CASE DESCRIPTION: We present an
      illustrative case of 'en bloc' excision of a highly vascular giant lateral
      sphenoid wing meningioma using the technique of 4 D's. After ruling out
      neurovascular encasement and significant brain interposition, our technique
      consisted of devascularization, diminutive dural opening, early detachment, and
      progressively deeper circumferential dissection. "En bloc" delivery was aided by
      the underlying brain pulsations and edema with no retraction or manipulation.
      This was successfully employed in a series of seven more patients with large
      meningiomas with less blood loss. All the patients recovered well with no
      clinical or radiological sequelae. CONCLUSION: In select large vascular
      meningiomas, en bloc excision appears to be a simple, safe, and effective
      alternative to piecemeal excision, which can be performed in any set-up.

PMID- 24032075
TI  - Glucocorticoids Reduce Renal NHE8 Expression.
AB  - The proximal tubule reabsorbs most of the filtered bicarbonate which is mediated
      in large part by Na+/H+ exchange (NHE). We have previously demonstrated that
      there is an isoform switch during postnatal maturation from NHE8 to NHE3 that is
      concordant with the postnatal increase in serum glucocorticoid levels. To examine
      if glucocorticoids may be responsible for this isoform switch, we administered
      dexamethasone daily to mice at 7-10 days of age, a time prior to the normal
      isoform switch. We show that compared to vehicle treated controls, dexamethasone
      caused a premature increase in renal NHE3 and decrease in NHE8 mRNA, total
      protein and brush border membrane protein abundance. To examine if there was a
      direct epithelial action of dexamethasone on NHE8, we studied NRK cells in vitro
      which express NHE8 on their apical membrane. Dexamethasone decreased NHE8 mRNA,
      total protein, and apical protein abundance. Dexamethasone also decreased Na+/H+
      exchanger activity. These studies provide evidence that glucocorticoids may play
      a role in the developmental isoform switch from NHE8 to NHE3 and cause a decrease
      in NHE8 expression and activity.

PMID- 24032078
TI  - Surgical management of traumatic extra dural hematoma in children: Experiences
      and analysis from 24 consecutively treated patients in a developing country.
AB  - BACKGROUND: Children with epidural hematoma (EDH) present differently than
      adults. The outcome of treatment is also different. We aim to report our
      experiences with EDH in pediatric age group in terms of mode of injury,
      presenting features, management, and outcomes. We also aim to identify different
      prognostic indicators in pediatric patients with EDH. METHODS: We prospectively
      collected data from 24 consecutively surgically treated pediatric patients. The
      data collected included presenting features, radiological imaging, details of
      management, and outcomes. Descriptive analysis was performed and different
      variables were tested for any statistical significance with Glasgow Outcome Score
      (GOS). RESULTS: There were 19 male and 5 female patients. The mean Glasgow Coma
      Scale (GCS) score at presentation was 9.3 +/- 4.4. Falls were the most common
      cause of EDH. Outcome assessment was done at 3 month follow up. A total of 15
      patients had a GOS score of 5, 4 patients had a GOS score of 4, 2 patients had a
      GOS score of 3, while 3 patients had a GOS score of 1. On univariate analysis,
      admitting GCS score, patient's age, the time from injury to admission and injury
      to surgery, anisocoric pupils at presentation and effacement of basal cisterns
      were significantly associated with the outcome of GOS score. CONCLUSION: Falls
      are the most common mode of injury leading to EDH in children. Lower GCS at
      presentation, younger age at trauma, increased time since trauma to surgery and
      admission, anisocoria and effacement of basal cisterns are statistically
      significant variables in surgically treated pediatric patients of EDH that confer
      a poorer prognosis. A timely surgical intervention can result in excellent
      outcomes.

PMID- 24032079
TI  - Usefulness of embolization of the middle meningeal artery for refractory chronic
      subdural hematomas.
AB  - BACKGROUND: Chronic subdural hematoma (CSDH) is generally treated by burr hole
      irrigation. However, sometimes repeated recurrence is observed, and treatment may
      consequently become difficult. We examined the efficacy of embolization of the
      middle meningeal artery (MMA) for such cases. METHODS: We considered embolization
      of the MMA for three patients who had refractory CSDH with repeated recurrence
      and two CSDH patients who were at risk of recurrence and showed signs of
      recurrence after surgery. A microcatheter was advanced through the MMA as
      peripherally as possible, and embolization was performed with 15-20% n-butyl-2
      cyanoacrylate or 200 MUm polyvinyl alcohol particles. RESULTS: EMBOLIZATION WAS
      PERFORMED IN THE THREE PATIENTS WHO HAD REFRACTORY CSDH WITH REPEATED RECURRENCE:
      The procedure was performed after burr hole irrigation of the hematoma in two
      patients and before the irrigation in one patient. In the two CSDH patients at
      risk of recurrence, embolization was performed when signs of recurrence appeared.
      The timing of embolization differed for each patient. However, in all the
      patients, the hematoma tended to decrease in size, and no recurrence was
      observed. CONCLUSION: Embolization of the MMA is effective for refractory CSDH or
      CSDH patients with a risk of recurrence, and is considered an effective
      therapeutic method to stop hematoma enlargement and promote resolution.

PMID- 24032080
TI  - General anesthesia versus combined epidural/general anesthesia for elective
      lumbar spine disc surgery: A randomized clinical trial comparing the impact of
      the two methods upon the outcome variables.
AB  - BACKGROUND: General anesthesia (GA) is the most frequently used technique for
      lumbar spine disc surgery. The aim of this study was to compare the
      intraoperative variables and postoperative outcome after GA and combined
      general/epidural anesthesia (CEG) in patients undergoing elective lumbar spine
      disk surgery. METHODS: Eighty patients who underwent one or two level of
      laminectomy/discectomy during a 2 year period were enrolled in this randomized
      controlled trial (RCT). They were randomly selected to undergo GA or CEG. The
      data recorded during surgery were: The patients' heart rate (HR), mean arterial
      blood pressure (MABP), amount of blood loss, and the medication used during
      anesthesia. The severity of pain score, total analgesic consumption, and
      complications were recorded in the postoperative period. RESULTS: The MABP, HR,
      blood loss, and anesthetic medication were significantly lower in CEG group in
      comparison with that of GA group. In the postoperative period, the pain score and
      total analgesic requirement was lower in the CEG group and less complication were
      encountered in this group. CONCLUSION: The results of this study revealed that
      CEG have some advantages over GA in reducing the blood loss and anesthetic
      medication during the operation and it is also more effective in control of pain
      with fewer complications during the postoperative period.

PMID- 24032081
TI  - The utility of ionotropic glutamate receptor antagonists in the treatment of
      nociception induced by epidural glutamate infusion in rats.
AB  - BACKGROUND: The authors have previously demonstrated that human herniated disc
      material contains high concentrations of free glutamate. In an experimental
      model, elevated epidural glutamate concentrations in the lumbar spine can cause a
      focal hyperesthetic state. METHODS: Rats underwent epidural glutamate infusion in
      the lumbar spine by a miniosmotic pump over a 72-hour period. Some rats underwent
      coinfusion with glutamate and ionotropic glutamate antagonists. Nociception was
      assessed by von Frey fibers and by assessment of glutamate receptor expression in
      the corresponding dorsal horn of the spinal cord. RESULTS: The kainic acid
      antagonist, UBP 301, decreased epidural glutamate-based hyperesthesia in a dose
      dependent manner. Concordant with these findings, there was significant decrease
      in kainate receptor expression in the dorsal horn. The N-Methyl-4
      isoxazoleproionic acid (NMDA) antagonist Norketamine also significantly
      diminished hyperesthesia and decreased receptor expression in the dorsal horn.
      CONCLUSIONS: Both UBP 301, the kainic acid receptor antagonist and Norketamine,
      an NMDA receptor antagonist, dampened epidural glutamate-based nociception. Focal
      epidural injections of Kainate or NMDA receptor antagonists could be effective
      treatments for disc herniation-based lumbar radiculopathy.

PMID- 24032082
TI  - Intraorbital arteriovenous fistula with thrombosed varix: Diagnosis and treatment
      without catheter angiography in a developing country.
AB  - BACKGROUND: Pure intraorbital arteriovenous fistula (AVF) that do not connect to
      the cavernous sinus are quite rare. Presence of thrombosed varix in association
      with a spontaneous onset pure orbital AVF is even rarer. CASE DESCRIPTION: We
      report an interesting case of a 50-year-old female with pure intraorbital AVF of
      spontaneous onset with thrombosed varicose superior ophthalmic vein (SOV). She
      presented with 18 months history of right eye proptosis, upper lid swelling, and
      conjunctival chemosis with recent onset of retro-orbital pain and decreased
      vision. Computed tomography (CT) and angiography revealed thrombosed varicose SOV
      in association with pure intraorbital AVF. Direct surgical exposure of the
      thrombosed SOV through right fronto-orbital approach followed by excision of the
      fistulous lesion resulted in complete orbital decompression with disappearance of
      all symptoms by 2 months. CONCLUSION: Spontaneous onset pure intraorbital AVF in
      association with thrombosed varicose SOV is extremely rare. In such cases, direct
      surgical exposure of the SOV followed by excision may accomplish complete closure
      of the fistula without significant risk for iatrogenic injury.

PMID- 24032083
TI  - Incarcerated spinal cord: A preventable surgical debacle.

PMID- 24032084
TI  - Resolving controversies in neurosurgery through randomized controlled trials.

PMID- 24032085
TI  - The value of extended glioblastoma resection: Insights from randomized controlled
      trials.

PMID- 24032086
TI  - Multiple brain metastases in a patient with uterine papillary serous
      adenocarcinoma: Treatment options for this rarely seen metastatic brain tumor.
AB  - BACKGROUND: Uterine papillary serous adenocarcinoma (UPSAC) occurs 10-fold less
      frequently than endometrial carcinoma, and is referred to type 2 endometrial
      adenocarcinoma. The prognosis of UPSAC is worse than that of type I endometrial
      carcinoma. Herein we report what is only the second case of UPSAC, but it should
      prove to be more informative than the first reported case. CASE DESCRIPTION: A 71
      year-old female had three different metastases in the brain; two of the
      metastases were located in the posterior fossa within the cerebellar parenchyma
      with perilesional edema, but no mass effect, and the third metastasis was located
      in the right frontal lobe, and caused hemispheric edema and subfalcine
      herniation. The lesion that caused mass effect was completely extirpated without
      any surgical complications. The patient's recovery was excellent. She is able to
      walk independently, and use her left hand and left arm. Her Karnofsky performance
      score 5 months postsurgery was 80/100. CONCLUSION: Based on the outcome in the
      presented case, we think that in any UPSAC patient with a metastatic brain tumor
      causing mass effect the symptomatic metastatic tumor must be removed, regardless
      of disease grade, to ensure optimal quality of life.

PMID- 24032087
TI  - Crystal storing histiocytosis presenting as a temporal lobe mass lesion.
AB  - BACKGROUND: Crystal storing histiocytosis (CSH) is a disorder characterized by
      local or diffuse infiltration of histiocytes containing crystalline inclusions
      most commonly of immunoglobulin light chain. Involvement of the central nervous
      system is extremely rare. CSH may be misdiagnosed as an infection or tumor. In
      patients with involvement of other organs, it is frequently associated with
      lymphoplasmacytic diseases. CASE DESCRIPTION: A 20-year-old female was evaluated
      for 2 weeks of progressively worsening headaches. At presentation, she had no
      history of fevers but reported a sore throat without cough 3-4 days prior. Her
      past medical history was unremarkable. She denied intravenous drug use or
      sexually transmitted diseases but lived with an individual with a history of
      fungal meningitis. On examination she was afebrile, alert, and oriented with a
      blood pressure of 110/70 mmHg. She had no adenopathy or neurological deficits.
      Her white blood cell count was minimally elevated. Magnetic resonance imaging
      revealed a 3.5 * 1.3 * 1.9 cm contrast enhancing lesion of the left temporal lobe
      with a mild midline shift. Evaluation by multiple specialists suggested a
      differential diagnosis of an infectious or neoplastic process. Cultures for
      infectious agents were negative. The biopsy showed CSH. Postoperatively and at 1
      month follow up, she was neurologically intact. CONCLUSION: Radiographically and
      intraoperatively, CSH may mimic an infectious process or neoplasm. Its
      recognition is critical to facilitate appropriate therapy and prompt screening
      for an occult lymphoplasmacytic neoplasm, plasma cell dyscrasia or other
      underlying disease.

PMID- 24032088
TI  - Adherence to Antiretroviral Therapy for the Success of Emerging Interventions to
      Prevent HIV Transmission: A Wake up Call.
AB  - Despite recent successes in several HIV prevention trials, the epidemic continues
      to increase in many countries. The most successful biomedical interventions to
      prevent HIV have been the use of Antiretroviral Therapy (ART) to Prevent Mother
      To-Child Transmission (PMTCT), and sexual transmission via microbicides,
      PreExposure Prophylaxis (PrEP), and treatment of the infected person within
      discordant couples. In addition medical male circumcision has also been shown to
      be highly effective in prevention of HIV acquisition. However, emerging data
      demonstrate that adherence to several of these prevention interventions is
      critical. ART adherence during and after pregnancy has been shown to be
      significantly below that recommended for adequate virologic suppression,
      particularly during the postpartum period. Five recent PrEP trials also
      demonstrate that the success of PrEP as a public health intervention will
      necessitate monitoring ART adherence and will include additional interventions to
      improve or maintain adherence to optimal levels. New successes in HIV prevention
      research have been tempered by suboptimal adherence. There is a critical need to
      define practical and effective adherence monitoring strategies as well as
      controlled trials of adherence interventions in the era of PrEP, Treatment as
      Prevention (TasP), and PMTCT to maximize their benefit.

PMID- 24032089
TI  - Fixed dystonia of the left hand in a violinist: a rare functional disorder.
AB  - BACKGROUND: Fixed dystonia leads to an immobile abnormal posturing of the
      affected limb. There is an ongoing debate whether this condition is psychogenic
      in origin. CASE REPORT: We present a 21-year-old violinist with fixed dystonia
      after an acute overuse injury with a transient cyanosis but no signs for
      psychological trauma. After Incobotulinumtoxin injection, symptoms subsided
      within 8 hours. DISCUSSION: Our case corroborates the notion that fixed dystonias
      after minor injuries are functional disorders. It underlines the necessity of a
      biopsychosocial approach to functional disorders, considering the possibility of
      an overlay between organic and non-organic disorders.

PMID- 24032091
TI  - Polyphyly and hidden species among Hawai'i's dominant mesophotic coral genera,
      Leptoseris and Pavona (Scleractinia: Agariciidae).
AB  - Widespread polyphyly in stony corals (order Scleractinia) has prompted efforts to
      revise their systematics through approaches that integrate molecular and
      micromorphological evidence. To date, these approaches have not been
      comprehensively applied to the dominant genera in mesophotic coral ecosystems
      (MCEs) because several species in these genera occur primarily at depths that are
      poorly explored and from which sample collections are limited. This study is the
      first integrated morphological and molecular systematic analysis of the genera
      Leptoseris and Pavona to examine material both from shallow-water reefs (<30 m)
      and from mid- to lower-MCEs (>60 m). Skeletal and tissue samples were collected
      throughout the Hawaiian Archipelago between 2-127 m. A novel mitochondrial marker
      (cox1-1-rRNA intron) was sequenced for 70 colonies, and the micromorphologies of
      94 skeletons, plus selected type material, were analyzed. The cox1-1-rRNA intron
      resolved 8 clades, yet Leptoseris and Pavona were polyphyletic. Skeletal
      micromorphology, especially costal ornamentation, showed strong correspondence
      and discrete differences between mitochondrial groups. One putative new
      Leptoseris species was identified and the global depth range of the genus Pavona
      was extended to 89 m, suggesting that the diversity of mesophotic scleractinians
      has been underestimated. Examination of species' depth distributions revealed a
      pattern of depth zonation: Species common in shallow-water were absent or rare
      >40 m, whereas others occurred only >60 m. These patterns emphasize the
      importance of integrated systematic analyses and more comprehensive sampling by
      depth in assessing the connectivity and diversity of MCEs. 

PMID- 24032092
TI  - Effect of stimulus width on simultaneous contrast.
AB  - Perceived brightness of a stimulus depends on the background against which the
      stimulus is set, a phenomenon known as simultaneous contrast. For instance, the
      same gray stimulus can look light against a black background or dark against a
      white background. Here we quantified the perceptual strength of simultaneous
      contrast as a function of stimulus width. Previous studies have reported that
      wider stimuli result in weaker simultaneous contrast, whereas narrower stimuli
      result in stronger simultaneous contrast. However, no previous research has
      quantified this relationship. Our results show a logarithmic relationship between
      stimulus width and perceived brightness. This relationship is well matched by the
      normalized output of a Difference-of-Gaussians (DOG) filter applied to stimuli of
      varied widths. 

PMID- 24032093
TI  - On the reproducibility of science: unique identification of research resources in
      the biomedical literature.
AB  - Scientific reproducibility has been at the forefront of many news stories and
      there exist numerous initiatives to help address this problem. We posit that a
      contributor is simply a lack of specificity that is required to enable adequate
      research reproducibility. In particular, the inability to uniquely identify
      research resources, such as antibodies and model organisms, makes it difficult or
      impossible to reproduce experiments even where the science is otherwise sound. In
      order to better understand the magnitude of this problem, we designed an
      experiment to ascertain the "identifiability" of research resources in the
      biomedical literature. We evaluated recent journal articles in the fields of
      Neuroscience, Developmental Biology, Immunology, Cell and Molecular Biology and
      General Biology, selected randomly based on a diversity of impact factors for the
      journals, publishers, and experimental method reporting guidelines. We attempted
      to uniquely identify model organisms (mouse, rat, zebrafish, worm, fly and
      yeast), antibodies, knockdown reagents (morpholinos or RNAi), constructs, and
      cell lines. Specific criteria were developed to determine if a resource was
      uniquely identifiable, and included examining relevant repositories (such as
      model organism databases, and the Antibody Registry), as well as vendor sites.
      The results of this experiment show that 54% of resources are not uniquely
      identifiable in publications, regardless of domain, journal impact factor, or
      reporting requirements. For example, in many cases the organism strain in which
      the experiment was performed or antibody that was used could not be identified.
      Our results show that identifiability is a serious problem for reproducibility.
      Based on these results, we provide recommendations to authors, reviewers, journal
      editors, vendors, and publishers. Scientific efficiency and reproducibility
      depend upon a research-wide improvement of this substantial problem in science
      today. 

PMID- 24032090
TI  - The neuropsychiatry of hyperkinetic movement disorders: insights from
      neuroimaging into the neural circuit bases of dysfunction.
AB  - BACKGROUND: Movement disorders, particularly those associated with basal ganglia
      disease, have a high rate of comorbid neuropsychiatric illness. METHODS: We
      consider the pathophysiological basis of the comorbidity between movement
      disorders and neuropsychiatric illness by 1) reviewing the epidemiology of
      neuropsychiatric illness in a range of hyperkinetic movement disorders, and 2)
      correlating findings to evidence from studies that have utilized modern
      neuroimaging techniques to investigate these disorders. In addition to diseases
      classically associated with basal ganglia pathology, such as Huntington disease,
      Wilson disease, the neuroacanthocytoses, and diseases of brain iron accumulation,
      we include diseases associated with pathology of subcortical white matter tracts,
      brain stem nuclei, and the cerebellum, such as metachromatic leukodystrophy,
      dentatorubropallidoluysian atrophy, and the spinocerebellar ataxias. CONCLUSIONS:
      Neuropsychiatric symptoms are integral to a thorough phenomenological account of
      hyperkinetic movement disorders. Drawing on modern theories of cortico
      subcortical circuits, we argue that these disorders can be conceptualized as
      disorders of complex subcortical networks with distinct functional architectures.
      Damage to any component of these complex information-processing networks can have
      variable and often profound consequences for the function of more remote neural
      structures, creating a diverse but nonetheless rational pattern of clinical
      symptomatology.

PMID- 24032094
TI  - Typhoon damage on a shallow mesophotic reef in Okinawa, Japan.
AB  - Little is known about effects of large storm systems on mesophotic reefs. This
      study reports on how Typhoon 17 (Jelawat) affected Ryugu Reef on Okinawa-jima,
      Japan in September 2012. Benthic communities were surveyed before and after the
      typhoon using line intercept transect method. Comparison of the benthic
      assemblages showed highly significant differences in coral coverage at depths of
      25-32 m before and after Typhoon 17. A large deep stand of Pachyseris foliosa was
      apparently less resistant to the storm than the shallower high diversity area of
      this reef. Contradictory to common perception, this research shows that large
      foliose corals at deeper depths are just as susceptible to typhoon damage as
      shallower branching corals. However, descriptive functional group analyses
      resulted in only minor changes after the disturbance, suggesting the high
      likelihood of recovery and the high resilience capacity of this mesophotic reef. 

PMID- 24032097
TI  - High-flexion posterior-stabilized total knee prosthesis: is it worth the hype?
AB  - High-flexion knee prosthesis was introduced with the aim of obtaining higher
      degree of flexion and good survivorship in patients with high functional demands
      or those requiring squatting, kneeling, etc., which is more common in Asians.
      Based on all the research and experience with this prosthesis, it was concluded
      that high flexion designs meet the need of deeper degrees of flexion in selected
      sets of patients only. Results were equal and comparable to the traditional
      standard posterior-stabilized total knee arthroplasty design and superior to it
      in terms of gaining more flexion and fulfilling activities, such as squatting,
      kneeling, and sitting cross-legged. 

PMID- 24032098
TI  - Translation and validation of the korean version of the international knee
      documentation committee subjective knee form.
AB  - PURPOSE: To perform a cross-cultural adaptation and to test the measurement
      properties of the Korean version of International Knee Documentation Committee (K
      IKDC) Subjective Knee Form. MATERIALS AND METHODS: According to the guidelines
      for cross-cultural adaptation, translation and backward translation of the
      English version of the IKDC Subjective Knee Form were performed. After
      translation into the Korean version, 150 patients who had knee-related problems
      were asked to complete the K-IKDC, Lysholm score, and Short Form-36 (SF-36). Of
      these patients, 126 were retested 2 weeks later to evaluate test-retest
      reliability, and 104 were recruited 3 months later to evaluate responsiveness.
      Construct validity was analyzed by investigating the correlation with Lysholm
      score and SF-36; content validity was also evaluated. Standardized mean response
      was calculated for evaluating responsiveness. RESULTS: The test-retest
      reliability proved excellent with a high value for the intraclass correlation
      coefficient (r=0.94). The internal consistency was strong (Cronbach's
      alpha=0.91). Good content validity with absence of floor not ceiling effects and
      good convergent and divergent validity were observed. Moderate responsiveness was
      shown (standardized mean response=0.689). CONCLUSIONS: The K-IKDC demonstrated
      good measurement properties. We suggest that this instrument is an excellent
      evaluation instrument that can be used for Korean patients with knee-related
      injuries.

PMID- 24032096
TI  - Infection following total knee arthroplasty.
AB  - For most orthopedists, total knee arthroplasty (TKA) has been regarded as the
      most effective surgery for patients with severe knee diseases. Though seldom
      occur, postoperative infection certainly remains one of the most devastating and
      dreaded complications of TKA. Thus, careful and early diagnosis is needed. After
      diagnosis, categorize the infection type and choose a rightful and sequential
      step of treatment are recommended. 

PMID- 24032099
TI  - Early Results of Total Knee Arthroplasty Using a Built-in 3-Degree External
      Rotation Prosthesis.
AB  - PURPOSE: We compared the outcomes of total knee arthroplasty (TKA) using the
      Genesis II prosthesis in which 3 degrees  of external rotation was incorporated
      into the femoral component and Nexgen LPS prosthesis in which the degree of
      external rotation was determined by the extent of intraoperative bone cutting.
      MATERIALS AND METHODS: Of the patients who underwent TKA for osteoarthritis
      between November 2006 and December 2009, 326 patients (572 knees) were included
      in this study. The prosthesis of choice was Genesis II in 199 knees and Nexgen
      LPS in 373 knees. The mean follow-up was 27 months (range, 24 to 51 months). The
      American Knee Society score (KSS) and function score (FS) were used for clinical
      assessments. The maximum flexion angle and patellar tilt were compared between
      the groups. RESULTS: At the final follow-up, no significant intergroup difference
      was observed regarding the KSS (p=0.217), FS (p=0.238), maximum flexion angle
      (p=0.124), and patellar tilt (p=0.156). CONCLUSIONS: There was no significant
      difference in the clinical outcomes and patellar tilt between the prosthesis in
      which 3 degrees  of external rotation was incorporated into the femoral component
      and the prosthesis in which external rotation was determined based on bone
      cutting.

PMID- 24032100
TI  - Comparison between Autogenous Bone Graft and Allogenous Cancellous Bone Graft in
      Medial Open Wedge High Tibial Osteotomy with 2-Year Follow-up.
AB  - PURPOSE: To compare the radiographic and clinical results of medial open wedge
      high tibial osteotomy (OWHTO) using autogenous bone graft and allogenous
      cancellous bone graft for medial compartment osteoarthritis of the knee with two
      year follow-up. MATERIALS AND METHODS: Fifty-one patients (52 knees) who
      underwent medial OWHTO from October 2007 to April. 2010 were included in the
      study. The patients were divided into group I (n=29) that received an autogenous
      tricortical bone graft and group II (n=23) that received an allogenous cancellous
      bone chip graft. The radiographic parameters (preoperative anatomical and
      mechanical femorotibial angles, modified tibial bone varus angle, and posterior
      tibial slope), clinical parameters, bone union period, and complications were
      evaluated from medical records. RESULTS: The radiographic and clinical outcomes
      did not show significant difference between two groups. The average bone union
      period was 11.7 weeks in group I and 12.1 weeks in group II. The visual analog
      scale score on the first postoperative day was significantly higher in group I
      than group II. CONCLUSIONS: Medial OWHTO using allogenous cancellous bone graft
      for medial compartment osteoarthritis of the knee can be considered as an
      alternative treatment method that provides equivalent radiographic and clinical
      results of OWHTO using autogenous bone graft and causes less immediate
      postoperative pain.

PMID- 24032095
TI  - Photoacoustic Imaging for Cancer Detection and Staging.
AB  - Cancer is one of the leading causes of death in the world. Diagnosing a cancer at
      its early stages of development can decrease the mortality rate significantly and
      reduce healthcare costs. Over the past two decades, photoacoustic imaging has
      seen steady growth and has demonstrated notable capabilities to detect cancerous
      cells and stage cancer. Furthermore, photoacoustic imaging combined with
      ultrasound imaging and augmented with molecular targeted contrast agents is
      capable of imaging cancer at the cellular and molecular level, thus opening
      diverse opportunities to improve diagnosis of tumors, detect circulating tumor
      cells and identify metastatic lymph nodes. In this paper we introduce the
      principles of photoacoustic imaging, and review recent developments in
      photoacoustic imagingas an emerging imaging modality for cancer diagnosis and
      staging.

PMID- 24032101
TI  - Proprioception and clinical results of anterolateral single-bundle posterior
      cruciate ligament reconstruction with remnant preservation.
AB  - PURPOSE: To evaluate the clinical and radiological results and proprioception
      following anterolateral single-bundle posterior cruciate ligament (PCL)
      reconstruction with remnant preservation for PCL injury. MATERIALS AND METHODS:
      Twenty patients with an isolated PCL injury (16 males and 4 females) were
      included in this study. The mean follow-up period was 61 months (>=24 months) and
      the mean age of the patients was 36 years. Knee joint instability was evaluated
      using posterior drawer stress radiography. Knee function, level of activities,
      and individual satisfaction were assessed using the Lysholm knee score, Tegner
      activity score, and 2000 International Knee Documentation Committee (IKDC) score.
      Knee proprioception was assessed using an isokinetic machine. RESULTS: The mean
      ligament laxity assessed using the posterior drawer stress radiography was
      improved from 10.8-3.2 mm. The mean Lysholm knee score was improved from 70.0
      88.9 points, and the mean Tegner activity score was improved from 2.7-6.2 points.
      Individual satisfaction assessed using the IKDC score was improved from 62.7-85.4
      points (p<0.05). Knee proprioception was not significantly different between the
      treated and the uninjured knees. CONCLUSIONS: Single-bundle PCL reconstruction
      with remnant preservation for PCL injury exhibited satisfactory outcomes
      regarding functional outcome, joint stability, and proprioception.

PMID- 24032102
TI  - Clinical results comparing transtibial technique and outside in technique in
      single bundle anterior cruciate ligament reconstruction.
AB  - PURPOSE: To compare the clinical results of single-bundle anterior cruciate
      ligament (ACL) reconstruction using the conventional transtibial technique and
      the anatomical outside-in technique for femoral tunneling. MATERIALS AND METHODS:
      From 2007 to 2011, 89 patients who received ACL reconstruction were followed for
      >=1 year were enrolled in the study. The conventional transtibial technique was
      used in 41 patients and the outside-in technique, in 48 patients. Femoral tunnel
      angle measurement and three-dimensional computed tomography (3D CT) were used for
      radiologic assessment of the location of femoral tunnel and Lysholm score and
      other tests were used for clinical assessment. RESULTS: Both techniques did not
      reveal statistical differences in the clinical assessment. However, in
      International Knee Documentation Committee subjective knee evaluation, the sum of
      two questionnaire items regarding instability showed a statistically significant
      difference (p=0.01). In the pivot shift test, the anatomical outside-in technique
      showed outstanding rotational stability over the transtibial technique (p=0.04).
      The mean femoral tunnel inclination in coronal plane were 69.2 degrees  and 30.3
      degrees , respectively, for both techniques, and 21.6 degrees  and 50.8 degrees ,
      respectively in sagittal plane, showing statistically significant differences on
      simple radiography (p=0.04, 0.05). A 3D CT was performed in 17 patients with the
      conventional transtibial technique and 25 patients with the outside-in technique.
      Coefficients of variation were 0.33 and 0.13, respectively, from dorsal border of
      the condyle and 0.67 and 0.24, respectively, from the roof of intercondylar
      notch. CONCLUSIONS: Femoral tunnels created with the outside-in technique have
      superior knee joint rotational stability compare to the transtibial technique.
      Therefore, the outside-in technique could be considered as a valuable technique
      in single-bundle ACL reconstruction.

PMID- 24032103
TI  - Primary total knee arthroplasty for simple distal femoral fractures in elderly
      patients with knee osteoarthritis.
AB  - PURPOSE: Primary total knee arthroplasty (TKA) can be an alternative method for
      treating distal femoral fractures in elderly patients with knee osteoarthritis.
      The purpose of this study was to evaluate the clinical and radiographic results
      in patients with knee osteoarthritis who underwent TKA with the Medial Pivot
      prosthesis for distal femoral fractures. MATERIALS AND METHODS: Eight displaced
      distal femoral fractures in 8 patients were treated with TKA using the Medial
      Pivot prosthesis and internal fixation. The radiographic and clinical evaluations
      were performed using simple radiographs and Hospital for Special Surgery (HSS)
      knee scores during a mean follow-up period of 49 months. RESULTS: All fractures
      united and the mean time to radiographic union was 15 weeks. The mean range of
      motion of the knee joint was 114.3 degrees  and the mean HSS knee score was 85.1
      at the final follow-up. CONCLUSIONS: Based on the radiographic and clinical
      results, TKA with internal fixation can be considered as an option for the
      treatment of simple distal femoral fractures in elderly patients who have
      advanced osteoarthritis of the knee with appropriate bone stock.

PMID- 24032104
TI  - A new surgical technique of arthroscopic partial meniscectomy for unstable
      inferior leaf of the anterior horn in a horizontal tear of lateral meniscus.
AB  - We introduce a new arthroscopic partial meniscectomy technique using a three
      portals and a small skin hook retractor to remove unstable inferior leaf in
      horizontal meniscal tear that involved the anterior portion of the lateral
      meniscus. The patient is positioned for a standard knee arthroscopy. After
      careful estimation of the depth and extent of the cleft and stability of the
      superior and inferior leaves is done through the standard anteromedial portal, a
      small skin hook retractor is inserted through the standard anterolateral portal
      to raise the dominant superior leaf of anterior horn, then the unstable inferior
      leaf is excised with a 90 degrees  rotary punch and a motorized shaver through
      the extreme far anteromedial portal. This technique is useful method to remove
      unstable inferior leaf of anterior horn of lateral meniscus which is difficult to
      remove with a standard technique. 

PMID- 24032105
TI  - Osteonecrosis of the knee after arthroscopic partial meniscectomy.
AB  - Osteonecrosis of the femoral condyle is known as an uncommon complication after
      arthroscopic meniscectomy. The lesion of osteonecrosis can be irreversible, thus
      early detection of the disease is crucial for treatment. A 50-year-old male
      patient without known risk factors of osteonecrosis developed increasing knee
      pain after arthroscopic partial meniscectomy. Magnetic resonance imaging showed
      rapid progression of osteonecrosis of the medial femoral condyle.
      Unicompartmental knee arthroplasty was performed after 9 months of conservative
      therapy. The patient is now free from pain during daily activities. It might be
      important to remind that if the patient's pain after arthroscopic partial
      meniscectomy is severe than expected, clinical doctors should pay attention to
      the possibility of ongoing osteonecrosis of the femoral condyle. 

PMID- 24032106
TI  - The Addition of All-Trans Retinoic Acid to Chemotherapy May Not Improve the
      Outcome of Patient with NPM1 Mutated Acute Myeloid Leukemia.
AB  - BACKGROUND: Previous studies have suggested that NPM1 mutations may be a marker
      for response to all-trans retinoic acid (ATRA) given as an adjunct to intensive
      chemotherapy in older patients with acute myeloid leukemia (AML). PATIENTS AND
      METHODS: We examined the impact of the addition of ATRA among patients with
      diploid cytogenetics treated on a randomized phase II study of fludarabine +
      cytarabine + idarubicine +/- G-CSF +/- ATRA with available data on their NPM1
      mutation status. Between September 1995 and November 1997, 215 patients were
      enrolled in the study. Among them, 70 patients had diploid cytogenetic and are
      the subjects of this analysis. RESULTS: The median age of the 70 patients was 66
      years (range 23-87). Twenty (29%) of patients had NPM1 mutations. Among them 7
      (35%) did and 13 (65%) did not receive ATRA in combination with chemotherapy.
      Complete remission (CR) was achieved in 71% of patients treated with ATRA as
      compared to 69% without ATRA (P = 0.62). With median follow-up of 12.5 years, the
      overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS)
      were similar among patients who received ATRA compared to no ATRA regardless of
      NPM1 mutation status. CONCLUSION: The addition of ATRA to intensive chemotherapy
      did not affect the overall outcome of patients with AML regardless of NPM1
      mutation status.

PMID- 24032107
TI  - Radiation Treatment for WHO Grade II and III Meningiomas.
AB  - The treatment of meningiomas is tailored to their histological grade. While World
      Health Organization (WHO) grade I lesions can be treated with either surgery or
      external beam radiation, WHO Grade II and III lesions often require a combination
      of the two modalities. For these high-grade lesions, conventional external beam
      radiation is delivered to either the residual tumor or the surgical resection
      margin. The optimal timing of radiation, either immediately following surgical
      resection or at the time of recurrence, is yet to be determined. Additionally,
      another method of radiation delivery, brachytherapy, can be administered locally
      at the time of surgery for recurrent lesions. Altogether, the complex nature of
      WHO grade II and III meningiomas requires careful treatment planning and delivery
      by a multidisciplinary team. 

PMID- 24032109
TI  - What should be done to increase survival in patients with colorectal cancer?

PMID- 24032110
TI  - Mechanical bowel preparation: keep it or abandon it?

PMID- 24032111
TI  - Serum carcinoembryonic antigen for recurrence in colorectal cancer patients.

PMID- 24032112
TI  - Timing of adjuvant chemotherapy in colorectal cancer patients.

PMID- 24032108
TI  - Microvesicles and intercellular communication in the context of parasitism.
AB  - There is a rapidly growing body of evidence that production of microvesicles
      (MVs) is a universal feature of cellular life. MVs can incorporate microRNA
      (miRNA), mRNA, mtDNA, DNA and retrotransposons, camouflage viruses/viral
      components from immune surveillance, and transfer cargo between cells. These
      properties make MVs an essential player in intercellular communication.
      Increasing evidence supports the notion that MVs can also act as long-distance
      vehicles for RNA molecules and participate in metabolic synchronization and
      reprogramming eukaryotic cells including stem and germinal cells. MV ability to
      carry on DNA and their general distribution makes them attractive candidates for
      horizontal gene transfer, particularly between multi-cellular organisms and their
      parasites; this suggests important implications for the co-evolution of parasites
      and their hosts. In this review, we provide current understanding of the roles
      played by MVs in intracellular pathogens and parasitic infections. We also
      discuss the possible role of MVs in co-infection and host shifting. 

PMID- 24032113
TI  - Investigation of clinical manifestations in korean colorectal cancer patients.
AB  - PURPOSE: Early diagnostic work-up in patients with clinical symptoms of
      colorectal cancer (CRC) is important to achieve good treatment results. In this
      study, we investigated clinical symptoms when a diagnosis of CRC was made in
      patients who had a surgical resection, especially focusing on the relevance of
      constipation to CRC. METHODS: The clinical symptoms of 17,415 CRC patients who
      had curative surgery from January 2010 to December 2012 were collected from 24
      training hospitals of surgery. RESULTS: The number of symptomatic patients before
      the diagnosis of CRC was 11,085 (63.7%). Hematochezia or melena, abdominal pain,
      anemia, and constipation were more often found in female than male patients while
      bowel habit change was more common in male patients. Considering age, bowel habit
      change and hematochezia or melena were more common in patients younger than 60.
      Anemia and constipation, however, were more common in patients older than 60.
      According to the group classification based on age, patients older than 60 had
      experienced more constipation (P = 0.049). Moreover, patients with constipation
      tended to have a more advanced disease status (P < 0.001). CONCLUSION: In
      patients who had surgery due to CRC, bleeding, abdominal pain, bowel habit change
      and constipation were the most frequent symptoms before diagnosis. Although
      whether or not constipation is a cause of CRC is unclear, it is one of the
      important clinical symptoms that presents in patients with CRC, and patients with
      a symptom of constipation tend to present with a more advanced CRC stage.

PMID- 24032114
TI  - Data on the characteristics and the survival of korean patients with colorectal
      cancer from the Korea central cancer registry.
AB  - PURPOSE: The incidence rates of colorectal cancer (CRC) in Korea have been
      increasing during the past decade. Therefore, it is important to understand the
      characteristics, including survival, of Korean CRC patients. The aim of this
      study was to use the nationwide cancer registry to evaluate the characteristics
      of Korean CRC, focusing on the survival, according to tumor location, sex, and
      specific age groups. METHODS: Using the Korea Central Cancer Registry (KCCR), we
      analyzed a total of 226,352 CRC cases diagnosed from 1993 to 2010. The five-year
      relative survivals were compared for the proximal colon, the distal colon, and
      the rectum. Survival rates were compared between men and women and between
      patients of young age (less than 40 years old) and patients of advanced age (70
      years old or older). RESULTS: The 5-year survival rates were improved in all
      subsites between 1993 and 2010. Distal colon cancer showed favorable survival
      compared to proximal colon or rectal cancer. Females demonstrated worse survival
      for local or regional cancers, and this difference was significant in for
      patients in their seventies. Young patients (<40 years old) showed better
      survival rates for overall and proximal colon cancer comparable to those for
      older patients (>=40 years old), but advanced age patients (>=70 years old) had
      worse survivals for all tumor subsites compared to their younger counterparts
      (<70 years old). These trends were similar in distant CRC. CONCLUSION: Korean CRC
      has certain distinct characteristics of survival according to tumor location,
      sex, and age. Despite the limitations of available data, this study contributes
      to a better understanding of survival differences in Korean CRC.

PMID- 24032115
TI  - Optimal time of initiating adjuvant chemotherapy after curative surgery in
      colorectal cancer patients.
AB  - PURPOSE: Adjuvant chemotherapy is routinely recommended for locally advanced
      colorectal cancer (CRC). There are very few data for the optimal starting date of
      adjuvant chemotherapy after the surgery. This study aimed to evaluate the
      effectiveness of earlier adoption of adjuvant chemotherapy after curative surgery
      for stage III CRC. METHODS: In this study, 159 patients with stage III CRC, who
      had undergone a curative resection, were enrolled retrospectively. Patients were
      categorized into 3 groups representing different timings to initiate the
      chemotherapy; less than 2 weeks (group 1), 3 to 4 weeks (group 2), and more than
      5 weeks (group 3). The overall survival rate (OS) and the relapse-free survival
      rate (RFS) were analyzed to evaluate the effectiveness of adjuvant chemotherapy.
      RESULTS: The 5-year OSs of the patients were 73.7% in group 1, 67.0% in group 2,
      and 55.2% in group 3. The 5-year RFSs of the patients were 48.8% in group 1,
      64.7% in group 2, and 57.1% in group 3. There were no significant differences in
      either the OS or the RFS (P = 0.200, P = 0.405). CONCLUSION: Starting
      chemotherapy earlier than 6 weeks after surgery does not show any significant
      difference. Thus, although adjuvant chemotherapy should preferably begin within 6
      weeks, the starting date should not necessarily be hastened, and the patient's
      general condition should be taken into consideration.

PMID- 24032116
TI  - Diagnostic Accuracy of Elevated Serum Carcinoembryonic Antigen for Recurrence in
      Postoperative Stage II Colorectal Cancer Patients: Comparison With Stage III.
AB  - PURPOSE: Elevated levels of serum carcinoembryonic antigen (CEA) following a
      curative resection of colorectal cancer (CRC) indicate recurrence; however, the
      levels of CEA may be elevated above the normal limit without recurrence. The aim
      of this study is to analyze the diagnostic accuracy of elevated serum CEA for
      predicting recurrence in postoperative stage II and stage III CRC patients.
      METHODS: A total of 336 stage II and stage III CRC patients who underwent a
      curative resection between January 2005 and October 2009 were enrolled.
      Sensitivities, specificities, positive predictive values (PPVs), negative
      predictive values (NPVs), likelihood ratios and post-test probabilities of
      recurrence associated with elevated CEA were analyzed and compared. RESULTS: The
      median follow-up duration was 45 months (36 to 134 months). Twenty-seven of 189
      stage II patients (14.3%) and 52 of 147 stage III patients (35.4%) developed
      recurrence during the follow-up period. Sensitivities, specificities, PPVs, and
      NPVs of elevated CEA were 37.0%, 91.4%, 41.7%, and 89.7%, respectively, in stage
      II patients and 46.2%, 90.5%, 72.7%, and 75.4% in stage III patients. Post-test
      probabilities of recurrence associated with elevated CEA were 41.8% in stage II
      patients and 71.9% in stage III patients. CONCLUSION: The predictive performance
      of the probability of recurrence associated with elevated serum CEA after a
      curative resection in stage II CRC patients is lower than that in stage III CRC
      patients.

PMID- 24032117
TI  - Mechanical bowel preparation and prophylactic antibiotic administration in
      colorectal surgery: a survey of the current status in Korea.
AB  - PURPOSE: The usefulness of mechanical bowel preparation (MBP) in colon surgery
      was recently challenged by many multicenter clinical trials and meta-analyses.
      The objectives of this study were to investigate current national opinions about
      MBP and prophylactic antibiotics (PA) and to provide preliminary data for
      developing future Korean guidelines for MBP and PA administration in colorectal
      surgery. METHODS: A questionnaire was mailed to 129 colorectal specialists. The
      questionnaires addressed the characteristics of the hospital, the MBP methods,
      and the uses of oral and intravenous antibiotics. RESULTS: A total of 73
      questionnaires (56.6%) were returned. First, in regard to MBP methods, most
      surgeons (97.3%) used MBP for a mean of 1.36 days. Most surgeons (98.6%)
      implemented whole bowel irrigation and used polyethylene glycol (83.3%). Oral
      antibiotic use was indicated in over half (52.1%) of the responses, the average
      number of preoperative doses was three, and the mean time of administration was
      24.2 hours prior to the operation. Finally, the majority of responders stated
      that they used intravenous antibiotics (95.9%). The responses demonstrated that
      second-generation cephalosporin-based regimens were most commonly prescribed, and
      75% of the surgeons administered these regimens until three days after the
      operation. CONCLUSION: The results indicate that most surgeons used MBP and
      intravenous antibiotics and that half of them administered oral PA in colorectal
      surgery preparations. The study recommends that the current Korean guidelines
      should be adapted to adequately reflect the medical status in Korea, to consider
      the medical environment of the various hospitals, and to establish more accurate
      and relevant guidelines.

PMID- 24032118
TI  - Colon cancer after acute diverticulitis treatment.
AB  - Diverticulitis is the most common clinical complication of diverticular disease,
      affecting 10-25% of the patients with diverticula. The prevalences of
      diverticulitis and colon cancer tend to increase with age and are higher in
      industrialized countries. Consequently, diverticulitis and colon cancer have been
      reported to have similar epidemiological characteristics. However, the
      relationship between these diseases remains controversial, as is the performance
      of routine colonoscopy after an episode of diverticulitis to exclude colon
      cancer. Recently, we experienced three cases of colon cancer after treating acute
      diverticulitis, based on which we suggest the importance of follow-up colonoscopy
      after acute diverticulitis. 

PMID- 24032119
TI  - Chronic pelvic abscedation after completion proctectomy in a rectal stump
      insufficiency; treatment with gracilis muscle flap following vacuum assisted
      closure therapy.
AB  - Presacral abscess formation due to rectal stump insufficiency following Hartmann
      procedure is very rare complication. If the abscess cavity is large, it might
      delay the reversal of the stoma and will probably result in a devastating future
      functioning of the neorectum. Moreover, very invasive treatments will be required
      in order to prevent severe septic complications. We present the case of a 58-year
      old man with a past history of Hartmann procedure for a low rectal carcinoma who
      presented with rectal stump insufficiency and a large presacral abscess.
      Following extensive debridement and rectal stump resection, a vacuum-assisted
      closure (VAC) system was applied to the large abscess cavity to facilitate
      gracilis muscle flap reconstruction and to optimize wound healing. The
      satisfactory results showed in the present report led us to favor a combination
      of VAC therapy and a gracilis muscle flap in intrapelvic and perineal
      reconstruction in the case of large defects associated with high risks of septic
      complications. 

PMID- 24032120
TI  - Incidental finding and management of intralobar sequestration of the lung in a 24
      year-old man.
AB  - Pulmonary sequestration is described as a dysplastic mass of lung tissue that
      lacks communication with the tracheobronchial tree and receives systemic rather
      than pulmonary arterial blood supply. Two distinct classifications, intralobar
      and extralobar, have been described. The present article discusses the etiology,
      clinical and radiographic features of pulmonary sequestration as well as the
      management of this condition when it is discovered incidentally. 

PMID- 24032121
TI  - Ice hockey lung - a case of mass nitrogen dioxide poisoning in the Czech
      Republic.
AB  - Nitrogen dioxide (NO2) is a toxic gas, a product of combustion in malfunctioning
      ice-resurfacing machines. NO2 poisoning is rare but potentially lethal. The
      authors report a case of mass NO2 poisoning involving 15 amateur ice hockey
      players in the Czech Republic. All players were treated in the Department of
      Respiratory Diseases at Brno University Hospital in November 2010 - three as
      inpatients because they developed pneumonitis. All patients were followed-up
      until November 2011. Complete recovery in all but one patient was achieved by
      December 2010. None of the 15 patients developed asthma-like disease or chronic
      cough. Corticosteroids appeared to be useful in treatment. Electric-powered ice
      resurfacing machines are preferable in indoor ice skating arenas.

PMID- 24032122
TI  - Diffuse intrapulmonary neuroendocrine cell hyperplasia.
AB  - Diffuse intrapulmonary neuroendocrine cell hyperplasia is a rare, potential
      precursor lesion to typical pulmonary carcinoid tumours. Fewer than 50 cases have
      been reported in the literature. Their pathogenesis, clinical significance and
      management is controversial. A patient who presented with diffuse intrapulmonary
      neuroendocrine cell hyperplasia associated with a primary typical carcinoid
      tumour of the lung is reported. 

PMID- 24032123
TI  - Severe asthma associated with myasthenia gravis.
AB  - Severe asthma constitutes a subgroup of approximately 10% of all asthma cases.
      Approximately one-half of these individuals have a refractory form of the disease
      in which atopy and T-helper cell 2-skewed immunological response may not be as
      closely linked to the disease as in other phenotypes of asthma. This suggests
      that not all asthma is explained by a T-helper cell 2-skewed immunological
      response, and that other immunological mechanisms may be important in this
      category of nonatopic asthma. The authors present a case involving a 55-year-old
      Caucasian man with nonatopic, adult-onset asthma, nonsteroidal anti-inflammatory
      drug sensitivity and idiopathic urticaria. This individual presented two years
      following his initial asthma diagnosis with diplopia and mild ptosis, and was
      subsequently diagnosed with seropositive myasthenia gravis. 

PMID- 24032125
TI  - Administration: A watchful eye on grant funding.

PMID- 24032124
TI  - Late onset and persistence of post-traumatic stress disorder symptoms in
      survivors of critical care.
AB  - BACKGROUND: Several recent studies have reported that post-traumatic stress
      disorder (PTSD) is a frequent occurrence in survivors of an intensive care unit
      (ICU) admission. OBJECTIVE: To assess the frequency of PTSD symptoms at three and
      nine months post-ICU admission and examine possible risk factors that predispose
      to the development of PTSD symptoms. METHOD: Using the following scales: Davidson
      Trauma Scale, Impact of Event Scale and the Post-traumatic Symptom Scale, 69 ICU
      survivors were assessed for PTSD symptoms at three months post-ICU admission. Of
      the original 69 patients, 37 completed the same questionnaires at the second
      follow-up at nine months post-ICU admission. Mean symptom levels for avoidance,
      intrusive thoughts and hyperarousal were calculated, and risk factors for the
      development of PTSD symptomatology were examined. RESULTS: Depending on which
      scale was used, 16% to 33% of ICU survivors met the criteria for PTSD at either
      three or nine months. Younger age and the use of a prescription psychoactive
      medication at time of ICU admission were both independently associated with a
      higher risk of developing PTSD symptoms. Interestingly, symptoms of hyperarousal
      worsened during the follow-up interval for female patients, while they remained
      constant for males. CONCLUSION: The frequency of PTSD symptoms was high in
      patients who survived an admission to the ICU. Depending on sex, symptoms may
      present and evolve differently. The adoption of screening tools and a multicentre
      ICU database in Canada is recommended to identify patients who are most at risk.

PMID- 24032126
TI  - Massive intravascular hemolysis with organ failure due to Clostridium
      perfringens: evidence of intracytoplasmic C. perfringens.

PMID- 24032127
TI  - Sideroblastic anemia secondary to zinc toxicity.

PMID- 24032129
TI  - Sequenced from the start.

PMID- 24032131
TI  - Reality at risk.

PMID- 24032130
TI  - Under threat.

PMID- 24032132
TI  - Policy: A single market for European research.

PMID- 24032133
TI  - Research: A standard for policy-relevant science.

PMID- 24032134
TI  - Health care: Bring on the evidence.

PMID- 24032135
TI  - Readmission reduction takes center stage.
AB  - As penalties for excess readmissions rise and more diagnoses are included in the
      program, case managers can play a major role in helping their hospitals avoid
      penalties. Take the time to complete a thorough assessment of patients and talk
      to their family members and caregivers to uncover psychosocial issues as well as
      medical issues and use the information to develop the discharge plan. Collaborate
      with post-acute providers to ensure that patients receive the services they need
      after discharge. When patients are readmitted, conduct a root-cause analysis to
      determine why they came back, track the data, and use it to develop process
      improvement projects.

PMID- 24032136
TI  - A proactive approach to preventing readmissions.

PMID- 24032137
TI  - Choose post-acute settings carefully.

PMID- 24032138
TI  - Study: interventions help prevent readmissions.
AB  - In a study by the Bronx Collaborative, patients who received two or more
      interventions by a dedicated care transition manager had a 17.6% readmission rate
      compared to a rate of 26.3% for patients who received the current standard of
      care. Three hospital systems and two health plans collaborated to develop the
      pilot project. Care transition managers, whose only job was facilitating
      transitions, visited patients in the hospital and followed up within 48 hours
      after discharge and again 14 days after discharge. The care transition managers
      educated the patients on their treatment plan, gave them a personalized booklet
      with details of their treatment plan, and followed up to answer questions and
      concerns and make sure they were following the plan.

PMID- 24032139
TI  - Transition CMs reduce readmissions from SNFs.
AB  - At Western Maryland Regional Medical Center, having nurse transitionists act as a
      liaison between the hospital and nursing facilities has reduced the readmission
      rate from participating facilities from 30% to 18%. The nurse transitionists
      carry a caseload of about 70 patients and work closely with the nursing home
      staff, patients, and family members to improve transitions. They follow patients
      who are admitted from a skilled nursing facility from the time they are admitted
      and patients who are going to a skilled nursing facility for the first time from
      the time that they are accepted into a bed and for 30 days after discharge. They
      visit the nursing home within 24 hours of transfer, meet with the patient,
      family, and staff and answer questions.They return on Day 5, between Day 11 and
      Day 14, and again at 25 to 30 days.

PMID- 24032140
TI  - A discombobulating reversal of dynamics--or an opportunity?

PMID- 24032141
TI  - Mobile computing. The doctor is in (and wants to get online).

PMID- 24032142
TI  - The IT Innovation Award first-place recipient: Neal Patel, M.D.

PMID- 24032144
TI  - Of physician documentation and disaster recovery. Interview by Mark Hagland.

PMID- 24032143
TI  - On the leading edge of cancer care and IT development. Interview by Mark Hagland.

PMID- 24032145
TI  - Alarm management as a patient safety goal.

PMID- 24032146
TI  - Take a breath.

PMID- 24032147
TI  - Fluid situation: Recent changes in the infusion pump market.

PMID- 24032148
TI  - Blood glucose meter inaccuracy presents risks.

PMID- 24032150
TI  - Services aim to assure Health App safety, quality.

PMID- 24032149
TI  - Irrelevant alarms: incidence, effects, and reduction methods.

PMID- 24032151
TI  - Communication of CT risks to patients is inadequate.

PMID- 24032152
TI  - High rate of missed errors by staff indicates need for improved EHR training.

PMID- 24032153
TI  - Aluminum rotating mechanism in double rotating pole clamps for Sigma Spectrum
      infusion pumps may wear and cause inadvertent rotation.

PMID- 24032154
TI  - Administration sets with antisiphon valves should be used to prevent potential
      uncontrolled gravity flow on B. Braun Infusomat Space pumps.

PMID- 24032156
TI  - Mettler MTD 4000 traction device's cable should be replaced every two years or
      when showing signs of wear.

PMID- 24032155
TI  - Midmark 411 examination table headlock arm can drive into the floor when lowering
      the table.

PMID- 24032157
TI  - Hospira plum series of volumetric infusion systems mixes primary and secondary
      fluids if not properly clamped.

PMID- 24032158
TI  - [Cosmonauts' tolerance of the chest-back G-loads during ballistic and
      automatically controlled descents of space vehicles].
AB  - Analysis of cosmonauts' +Gx tolerance on the stage of ballistic or automatically
      controlled Soyuz descent after missions to the International space station of
      varying duration was performed. As compared with automatically controlled
      descents, tolerance of descent re-entry +G(x) following short (8-14 d) missions
      was marked by reliably more frequent instances of visual disorders, difficult
      breathing, sensation of a lump in the throat and vestibulovegetative disorders (p
      < 0.05). The ballistic but not controlled re-entry after long-term mission
      provoked visual disorders, difficulties with breathing and speech, and
      vestibulovegetative disorders more often (p < 0.05). A considerable HR rise due
      to the ballistic rather than control descent was associated with re-entry and the
      main parachute re-hooking for symmetrical suspension; respiration rate was the
      highest during parachuting. By and large, these factual data infer that the
      ballistic descent after various periods in spaceflight microgravity, especially
      after extended space missions (164-169 d), led to a dramatic loss in the body
      functional reserves.

PMID- 24032159
TI  - [Association between the person-unique individual behavior styles and the quality
      and reliability of operator's professional performance].
AB  - Among the prioritized objectives of maintaining psychophysiological safety in
      extended space missions is the buildup of crew professional reliability.
      Reliability of operator's performance hinges as on skills level, so personal
      working style. The purpose of the investigation was to penetrate into the
      patterns of association between a person-unique individual behavior style and
      quality and reliability of simulated professional operator's jobs. The
      investigation was part of the MARS-500 experiment (RF SSC - IBMP RAS, 2010-2011)
      and employed 2 procedures: the well-established manual vehicle control (Pilot-1)
      and a new one tasking with planetary surface exploration (VIRTU). Observation of
      individual work styles resulted in identification of 2 fundamentally different
      approaches to handling the operator's duties--reliable and innovative. It is
      noteworthy that a separate participant adhered to one and the same style when
      coping with either procedure. Also, personality traits predisposing to a concrete
      behavior were found, which confirms the hypothesis of deep personal nature of
      operator's work style that reveals itself consistently and isomorphically no
      matter the type of important job.

PMID- 24032160
TI  - [Characteristics of the signal lag effect on crew--control center communications
      in the 520-day simulation experiment].
AB  - The 520-day experimental simulation of an exploration mission provided an
      opportunity to apply content analysis for studying the patterns of crew--Control
      center (CC) communication impeded by lag times. The period of high autonomy was
      featured by drastic reduction of the number of crew questions and requests which
      was judged as a marker of adaptation to the simulated space mission environment.
      The "key" events in the experiment changed the content of crew messages radically
      attesting to misperception of time, emotional involvement, want of CC feedback
      and draining out negative emotions. After the period of high autonomy with full
      loss of communication with controllers the traffic of crew messages onto the
      outside was noted to become very light which could also point to temporal changes
      in the communication style developed in the conditions of isolation and
      autonomous existence.

PMID- 24032161
TI  - [Control locus, stress resistance and personal growth of the participants in
      experiment Mars-500].
AB  - The article deals with positive personal transformations in a simulated space
      mission. The investigation was focused on the aspects of control locus, stamina,
      proactive behavior to overcome challenges, and stress-related personal growth.
      Besides, ingenious psychophysiological techniques designed to select Russian
      cosmonauts were used for assessing stress-resistance and ability to control own
      emotions voluntarily. Experiment Mars-500 simulated the basic features of a
      mission to Mars. The crew consisted of 6 males 27 to 38 years of age who
      volunteered to spend 520 days in isolation and confinement in the IBMP
      experimental facility (Moscow). To detect personality changes, the volunteers
      were tested before the experiment and after its completion. According to the test
      results, the participants commonly demonstrated the ability to see the bright
      side of the Mars-500 adversities, which most often was caused by their social
      growth. Positive changes were particularly pronounced in the crewmembers who
      possessed a better ability to control own emotions. The simulated challenges were
      also beneficial for personal growth of the volunteers.

PMID- 24032162
TI  - [Effect of physical countermeasures against support load deficiency on the
      hemostasis system in an experiment with 7-day immersion].
AB  - In an experiment with 7-d dry immersion for testing the mechanic foot and
      electrical muscle stimulation procedures of compensating the support load
      deficiency the following biochemical parameters were studied: activated partial
      thromboplastin time, prothrombin time, prothrombin index, international
      normalized ratio, thrombin time (TT), fibrinogen, soluble fibrin-monomer
      complexes, D-dimer (DD), plasminogen (PG); antithrombin III activity (ATIII),
      protein C (PC) and alpha2-antiplasmin (AP). Control subjects (immersed w/o
      stimulation) did not exhibit significant shifts in the hemostasis system:
      however, they decreased ATIII, PC and PG in the post-experimental period.
      Mechanic foot stimulation did not have a noteworthy effect on the hemostasis
      system functioning during immersion, whereas electromyostimulation increased
      procoagulant and fibrinolytic activity in blood plasma.

PMID- 24032163
TI  - [Stress-resistance and the condition of surfactant system and water balance in
      the lung of suspended rats].
AB  - White male rats with the body mass of 180-220 grams were distributed into the
      open-field active (presumably stress-resistant) and open-field inactive
      (presumably stress vulnerable) groups for a 10-day experimental suspension with
      the purpose to evaluate the surfactant activity in bronchoalveolar lavages, total
      phospholipids and their fractions, and water balance in the lung. In modeled
      microgravity, augmented blood filling of the rat's lung increases the alveolar
      phospholipid content and alters the phospholipid fractional composition in the
      pulmonary surfactant. Ten-day suspension raises pulmonary surfactant activity to
      a greater extent in stress-resistant animals rather than in their stress
      vulnerable peers.

PMID- 24032164
TI  - [Use of ion-exchange substrates for optimizing the mineral supply to plants
      within life support systems].
AB  - The main goal of the work is to validate ion-exchange substrates as optimizers of
      plant mineral supply within bio-engineering systems of life support with a high
      level of closure. Test objects were spring Lisovsky wheat-232 and leaf cabbage
      Sensuji-kyomizuna. Crops were cultivated on artificial soil (AS) in
      environmentally controlled plant growth chambers. Prior to seeding, AS was
      enriched simultaneously with wheat straw and ion-exchange substrate BIONA-312 to
      the extent of 2, 10 or 20% of AS dry mass. Incorporation of the ion-exchange
      substrate in the amount of 10% increased crop productivity and eliminated the
      negative effect of wheat straw. Ion-exchange substrate in amount of 20% did not
      yield a noticeable gain in productivity as compared with the previous test.

PMID- 24032165
TI  - [Clinico-diagnostic and expert characteristics of noncoronary cardiac rhythm
      disorders in state aviation pilots].
AB  - Structure and prevalence of various forms of noncoronary heart diseases (NCHD)
      and cardiac rhythm disorders (CRD) in state aviation pilots, as well as rates of
      ensuing grounding were studied. The total of 220 NCHD and 100 essentially healthy
      pilots were examined. Cardiovascular clinical and functional investigations
      consisted of physical examination, ECG, dispersion mapping (DM ECG), provocative
      tests and other techniques used for pilots' certification. Effectiveness of the
      clinical and instrumental methods of diagnosing arrhythmias was evaluated. CRD
      presence was verified by Holter monitoring. Extrasystoles prevalence was recorded
      in NCHD pilots; clinically significant forms of the diseases were commonly
      detected in pilots with chronic infections of the tonsils. In addition,
      radiodiagnostics of the immune status was applied to confirm the role of
      infection and immunology factor. DM ECG screening for differentiation between the
      norm and pathology was found useful in detecting early metabolic shifts and CVS
      functional evaluation. These results provided the basis for guidelines concerning
      medical expertise of pilots with noncoronary arrhythmias.

PMID- 24032166
TI  - [Effect of support deprivation on the sequence of motor units recruiting].
AB  - Motor units (MUs) activity in the knee extensors were tested by sustention of a
      small isometric effort in the conditions of foot support deprivation by dry
      immersion with simultaneous mechanic stimulation of the foot support zones.
      Analysis of MUs inter-pulse intervals (IPI) histograms in the heads of two leg
      extensors (m. soleus and m. gastrocnemius lat.) demonstrated that the MUs
      recruiting order is much dependent on the support input activity. In immersion,
      rearrangement of the sequence of MUs recruiting during the isometric effort
      sustention test pointed to a lower involvement of small tonic MUs; large MUs with
      IPIs as long as 260 ms and high variability took the place of small tonic MUs
      with relatively short IPIs (100 ms) and weak variability. Daily support
      stimulation in the timeframe of immersion was favorable to maintaining the normal
      pattern of MUs recruitment.

PMID- 24032167
TI  - [Effect of the life activity factors of long-duration isolation on the
      chromosomal apparatus of human blood lymphocytes in vivo].
AB  - The purpose was to study consequences of long-duration (105-day) isolation and
      confinement on the rate of chromosomal aberrations in human blood lymphocytes in
      vivo. Blood samples for cytogenetic analysis were drawn from 6 test-subjects
      before and on completion of the experiment. Analysis of unstable chromosomal
      aberrations showed a statistically reliable increase (p < 0.05) in the rate of
      chromatid aberrations (virtually, 25-fold) in the form of single fragments as
      compared with baseline values. Rate of chromosome aberrations did not differ from
      baseline values except 1 test-subject with a dicentric and associated fragment
      found after the experiment.

PMID- 24032168
TI  - [Bioethical review of biomedical research programs with human use in space
      medicine].

PMID- 24032169
TI  - [Development of aids for monitoring the vital functions of cosmonauts' organism
      in extended space flight].

PMID- 24032170
TI  - [Diagnosis and treatment of PFAPA syndrome].

PMID- 24032171
TI  - [Treatment of surfer's ear].

PMID- 24032172
TI  - Professor Anna Dyaczynska-Herman, the founder of the Silesian school of
      anaesthesiology and intensive therapy - on the 80th birthday anniversary.

PMID- 24032173
TI  - Management of cases of anticipated difficult intubation. Commentary on article M.
      Lasinska-Kowara et al.: "complications after using the Airtraq laryngoscope for a
      predicted difficult intubation".

PMID- 24032175
TI  - [Adaptation to hearing aid].

PMID- 24032174
TI  - Reply to commentary on article M. Lasinska-Kowara et al.: "complications after
      using the Airtraq laryngoscope for a predicted difficult intubation".

PMID- 24032177
TI  - Computed tomography alone reveals the secrets of ancient mummies in medical
      archaeology.

PMID- 24032176
TI  - Carbon-11-acetate positron emission tomography (PET), versus fluorine- 18
      fluorodeoxyglucose PET and CT for the diagnosis of recurrent prostate cancer
      after radical prostatectomy in cases of prostate specific antigen of more than 1
      to 3ng/mL.

PMID- 24032178
TI  - Vitamin and supplement do's and don'ts.

PMID- 24032179
TI  - The safe way to get rid of expired drugs.

PMID- 24032180
TI  - The facts about joint supplements.

PMID- 24032181
TI  - Other options to ease arthritis pain.

PMID- 24032182
TI  - FDA aims to limit arsenic in apple juice.

PMID- 24032183
TI  - [In memoriam: Dr. Kyaw Myint].

PMID- 24032184
TI  - [Treatment of ulcerative colitis with spleen and kidney yang deficiency by
      kuijiening plaster: a randomized controlled study].
AB  - OBJECTIVE: To explore the clinical efficacy of ulcerative colitis with spleen and
      kidney yang deficiency by kuijiening plaster and the impacts on IFN-gamma and IL
      4 contents, as well as make the comparison with oral medication of sulfasalzine
      (SASP). METHODS: Sixty patients of ulcerative colitis with spleen and kidney yang
      deficiency were randomized into a Kuijiening plaster group, a SASP group and a
      combined therapy group, 20 cases in each one. In the Kuijiening plaster group,
      Kuijiening plaster and oral administration of placebo SASP were applied. The
      plaster was used at Shangjuxu (ST 37), Tianshu (ST 25), Zusanli (ST 36), Mingmen
      (GV 4) and Guanyuan (CV 4). In the SASP group, was applied Kuijiening plaster
      placebo at the points and SASP oral administration was adopted. In the combined
      therapy group, Kuijiening plaster and SASP oral administration were given. The
      duration of treatment was 60 days. The follow-up visit was 2 months after
      treatment. The comprehensive efficacy, the efficacy on TCM syndrome and the
      changes in serum IFN-gamma and IL-4 before and after treatment were compared
      among the three groups. RESULTS: The efficacy on TCM syndrome in the Kuijiening
      plaster was similar to the SASP group [85.0% (17/20) vs 75.0% (15/20), P > 0.05].
      The efficacy on TCM syndrome in the Kuijiening plaster group was superior to the
      western medicine group [80.0% (16/20) vs 60.0% (12/20), P < 0.05]. The total
      effective rate of the comprehensive efficacy in the combined therapy group was
      95.0% (19/20) and that of TCM syndrome efficacy was 90.0% (18/20), which were all
      superior to the other two groups (all P < 0.05). The differences in serum IFN
      gamma and IL-4 were statistically significant before and after treatment in all
      of the three groups (all P < 0.05). The treatments in the three groups reduced
      serum IFN-gamma content and increased serum IL-4 content. The results in the
      Kuijiening plaster group were superior to the SASP group (P < 0.05) and the
      results in the combined therapy group were superior to the other two groups (all
      P < 0.05). CONCLUSION: Kuijiening plaster is effective in the treatment of
      ulcerative colitis of spleen and kidney yang deficiency, which is not inferior to
      that of SASP. The efficacy of kuijiening plaster on relieving TCM syndrome and
      improving body immunity is much superior to SASP. The effect is much better with
      SASP combined in the treatment.

PMID- 24032185
TI  - [Treatment of cervical spondylosis by spinal balancing combined with intervention
      of pathway of qi: a randomized controlled study].
AB  - OBJECTIVE: To compare the difference in the efficacy of cervical spondylosis
      between the combined therapy of spinal balancing and the intervention of pathway
      of qi and the conventional acupuncture and massage therapy. METHODS: Two hundred
      and seventy-four cases of cervical spondylosis were randomized into a spinal
      balancing group and a conventional acupuncture group, 137 cases in each one. In
      the spinal balancing group, the points on the pathway of qi on the head and on
      the abdomen were selected [the pathway of qi on the head: Baihui (GV 20), Tianzhu
      (BL 10), Wangu (GB 12) and the others; the pathway of qi on the abdomen: Shenshu
      (BL 23), Guanyuan (CV 4), Zhongji (CV 3) and the others]. The bimanual needling
      technique was applied in combination with spinal balancing therapy. In the
      conventional acupuncture group, the points were Jiaji (EX-B 2) (C3-C7), Fengchi
      (GB 20), Wangu (GB 12), Baihui (GV 20), etc. The conventional acupuncture
      technique and massage therapy were adopted. The neck pain questionnaire (NPQ) was
      adopted to assess the clinical efficacy of the two groups before and after
      treatment. RESULTS: NPQ score was all improved significantly after treatment in
      the two groups (all P < 0.05). The result in the spinal balancing group was
      superior to the conventional acupuncture group (P < 0.05). The curative and
      effective rate was 83.2% (114/137) in the spinal balancing group, which was
      better than 69.3% (95/137) in the conventional acupuncture group (P < 0.05). In
      terms of the types of cervical spondylosis, from high to low, the efficacy
      sequence was cervical type, nerve root type, vertebral artery type, sympathetic
      nerve type and spinal cord type. CONCLUSION: The combined therapy of spinal
      balancing and the intervention of pathway of qi achieves the superior efficacy on
      various types of cervical spondylosis as compared with the conventional
      acupuncture and massage therapy. It apparently relieves the symptoms and improves
      the life quality of the patients.

PMID- 24032187
TI  - [Efficacy observation on acupuncture prescription of regulating yin-yang and five
      viscera for intractable insomnia].
AB  - OBJECTIVE: To explore a more optimal therapy for intractable insomnia. METHODS:
      Seven hundred cases of intractable insomnia that were in accordance with the
      criteria were randomly divided into an observation group (368 cases) and a
      control group (332 cases). The acupuncture prescription of regulating yin-yang
      and five viscera was applied in the observation group, where Dazhui (GV 14),
      Shenmai (BL 62), Guanyuan (CV 4), Zhaohai (KI 6), Geshu (BL 17), etc. were
      selected. The acupuncture prescription of tranquilizing mind was applied in the
      control group, where Baihui (GV 20), Sishencong (EX-HN 1), Anmian (Extra),
      Shenmen (HT 7), Sanyin jiao (SP 6) were selected. The treatment was given once a
      day, ten times of which made a session. After the treatment for 4 sessions, the
      clinical efficacy and Pittsburgh sleep quality index (PSQI) were compared between
      two groups. RESULTS: The total effective rate was 92.6% (338/365) in the
      observation group, which was superior to 73.1% (242/331) in the control group (P
      < 0.05). The PSQI score was obviously decreased in two groups after the treatment
      (both P < 0.05), in which the decreasing in the observation group was superior to
      that in the control group (P < 0.05). CONCLUSION: The acupuncture prescription of
      regulating yin-yang and five viscera has better effect for intractable insomnia,
      which could be considered as a more optimal therapy.

PMID- 24032186
TI  - [Clinical research on post-stroke dysphagia treated with nape acupuncture and
      rehabilitation training].
AB  - OBJECTIVE: To observe the improvement in post-stroke dysphagia after treatment of
      nape acupuncture and rehabilitation training. METHODS: Eighty patients who were
      in compliance with the inclusive criteria were randomized into a conventional
      treatment group and a nape acupuncture group, 40 cases in each one, according to
      the admission sequence. In the conventional treatment group, on the basis of
      general medication, the rehabilitation training of swallowing function was
      applied. In the nape acupuncture group, on the basic treatment as the
      conventional treatment group, nape acupuncture group was given. RESULTS: After
      treatment, the improvements in bedside water swallowing test, SSA, VFSS and
      pharynx transit time were all superior to those before treatment for the patients
      in the two groups (all P < 0.05). The improvements in bedside water swallowing
      test, SSA, VFSS and pharynx transit time in the nape acupuncture group were all
      superior to those in the conventional treatment group (all P < 0.05). The total
      effective rate was 85.0% (34/40) in the nape acupuncture group, which was higher
      than 65.0% (26/40) in the conventional treatment group, indicating the
      significantly statistical difference between the two groups (P < 0.05).
      CONCLUSION: Nape acupuncture combined with rehabilitation training significantly
      improves swallowing function of the patients after stroke.

PMID- 24032188
TI  - [Impacts on tiptoe deformity and intelligent development in spasmodic cerebral
      palsy treated with acupuncture at naoqing xue (extra)].
AB  - OBJECTIVE: To assess the impacts on tiptoe deformity and intelligent development
      in spasmodic cerebral palsy treated with acupuncture at Naoqing Xue (Extra).
      METHODS: One hundred and forty-six children with spasmodic cerebral palsy were
      randomized into a Naoqing Xue group (74 cases) and a control group (72 cases). On
      the basic treatment (scalp acupuncture, sport therapy), in the Naoqing Xue group,
      acupuncture at Naoqing Xue (Extra) was applied. In the control group, acupuncture
      was given at Jiexi (ST 41), Yanglingquan (GB 34) and Sanyinjiao (SP 6). In the
      two groups, acupuncture was given once every two days, 10 treatments made one
      session, at the interval of 15 days between two sessions. Three sessions of
      treatment were given continuously. Before treatment and after 3 sessions of
      treatment, the angle measurement of ankle passive dorsiflexion, comprehensive
      spasm scale (CSS) and Gesell intelligence test were adopted for the
      rehabilitation assessment. Additionally, 30 min after the end of the first
      acupuncture treatment, the angle measurement of ankle passive dorsiflexion and
      CSS were applied to assess the immediate effect of the therapeutic methods of the
      two groups. RESULTS: The immediate effect of the angle measurement of ankle
      passive dorsiflexion and CSS as well as the effect after 3 sessions of treatment
      in the Naoqing Xue group were all superior to those in the control group (all P <
      0.05). In 3 sessions of treatment, the development quotients of social adaptive
      behavior and personal social activation function in Gesell intelligence test in
      the Naoqing Xue group were all higher than those in the control group (all P <
      0.05). The development quotients of major movement, fine motion and language were
      not different significantly as compared with those in the control group (P >
      0.05). CONCLUSION: Acupuncture at Naoqing Xue (Extra) relieves tiptoe deformity
      and promotes intelligent development for the children with spasmodic cerebral
      palsy.

PMID- 24032189
TI  - [Case of upper limb lymphedema after breast cancer operation].

PMID- 24032190
TI  - [Treatment experience of massage at Fengchi (GB 20), Anmian, Zhongwan (CV 12) for
      74 cases of insomnia].

PMID- 24032191
TI  - [Impacts on vertebral arterial blood flow of cervical spondylosis of vertebral
      artery type treated by abdominal acupuncture].
AB  - OBJECTIVE: To explore the therapeutic effect and mechanism of abdominal
      acupuncture for cervical spondylosis of vertebral artery type. METHODS: Thirty
      cases of cervical vertigo, in which the color ultrasonography indicated vertebral
      arterial blood insufficiency, were treated with abdominal acupuncture therapy.
      The points were Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), Xiawan (CV 10),
      Shangqu (KI 17) and Huaroumen (ST 24). The treatment was given once every day and
      five continuous treatments made one session. Separately, before treatment and in
      the 1st and 5th treatments, the cervical vertigo symptom and functional
      assessment scales were adopted for scoring. Simultaneously, the color
      ultrasonography was applied to observe the blood flow changes of the bilateral
      cervical arteries. RESULTS: Except the score for headache in the 1st treatment,
      the scores in cervical vertigo and function assessment scale in the 1st and 5th
      treatments were all improved significantly in 30 patients as compared with those
      before treatment (P < 0.01, P < 0.05). In the 1st and 5th treatments, on the
      affected side, the vertebral artery diameter, mean velocity and blood flow per
      minute were all improved significantly as compared with those before treatment
      (all P < 0.01). In one session treatment, the total effective rate was 100.0%
      (30/30) and the curative rate was 60.0% (18/30). CONCLUSION: Abdominal
      acupuncture therapy not only relieves the clinical symptoms, but also improves
      vertebral arterial blood supply for the patients of cervical spondylosis of
      vertebral artery type.

PMID- 24032192
TI  - [Observation on the therapeutic effect of lumbar disc herniation treated with
      different acupuncture therapies].
AB  - OBJECTIVE: To observe the differences in the clinical therapeutic effects on
      lumbar disc herniation among warm needling therapy, electroacupuncture therapy
      and common acupuncture therapy. METHODS: One hundred and thirty-six cases of
      lumbar disc herniation were randomized into a warm needling group (46 cases), an
      electroacupuncture group (45 cases) and a common acupuncture group (45 cases).
      The points were the same in the three groups. The main points were Shiqizhui (EX
      B 8), Yaoyangguan (GV 3), Huantiao (GB 30), Yanglingquan (GB 34), Jiaji (EX-B 2)
      (corresponding tender points). In the warm manipulation group, the warm and
      dredging manipulation was adopted. In the electroacupuncture group, G6805- II
      electric acupuncture apparatus was attached. In the common acupuncture group,
      only common needling therapy was applied without any specific manipulation
      supplemented. In all of the three groups, the treatment was given once every two
      days, 10 treatments made one session. After one session of treatment, the
      comprehensive assessment score of the chief symptoms and physical signs, VAS
      score and the clinical efficacy were compared among the three groups. RESULTS:
      The score of the chief symptoms and physical signs and VAS score after treatment
      were all reduced as compared with those before treatment in all of the three
      groups, indicating the statistically significant differences (P < 0.05). All of
      the three therapies could relieve the chief symptoms and physical signs of lumbar
      disc herniation. After treatment, the total effective rate was 89.1% (41/46) in
      the warm manipulation group, 88.9% (40/50) in the electroacupuncture group and
      71.1% (32/45) in the common acupuncture group. The efficacies were not different
      apparently between the warm manipulation group and the electroacupuncture group
      (P > 0.05). The efficacies in the warm manipulation group and the
      electroacupuncture group were all superior to the common acupuncture group (P <
      0.05). CONCLUSION: The efficacies of the warm and dredging manipulation and the
      electroacupuncture therapy are superior to the common acupuncture therapy in the
      treatment of lumbar disc herniation.

PMID- 24032193
TI  - [Treatment of autism children: observation on efficacy of behavior training with
      retention of needles on head].
AB  - OBJECTIVE: To observe the effect difference of behavior training with head
      needling retention and behavior training after acupuncture for autism children.
      METHODS: Sixty qualified autism children were divided randomly into simultaneous
      head needling retention and behavior training group (trial group) and behavior
      training after acupuncture treatment group (control group) with 30 case in each
      group. Retention needles on the head with simultaneous behavior training was
      applied for the trial group. The main acupoints included Sishen Xue, Dingshen
      Sanxue (3 points for mental tranquilization), Nao Sanxue (3 points for the
      function of brain), Shou Zhisanxue (3 points for mental activities on hand) and
      Zozhi Sonxue (3 points for mental activities on foot). Other points were combined
      according to conditions of patients. Needles on the 4 extremities were withdrawn
      first after 30 minutes, needles on head were remained during behavior training.
      While behavior training was applied to the control group when acupuncture
      treatment was completely accomplished. Treatments were applied once a day to both
      groups. And 3 months was taken as one observation cycle. Estimation was made on
      therapeutic effect and developing level of autism children with CARS and PEP.
      RESULTS: The total effective rate of the trial group was 83.3% (25/30), better
      than 66.7% (20/30) of the control group (P < 0.05). The CARS scores of both
      groups declined after the treatment. And the score of trail group was lower than
      the control group (all P < 0.05). While the PEP scores of both groups increased,
      and the score of trail group was higher than the control group (all P < 0.05).
      The increasing level of scores of cognitive understanding and cognitive
      expression were all better than the control group (all P < 0.05). CONCLUSION: The
      effect of behavior training with head needle retention on autism children is
      better than behavior training after acupuncture treatment, especially in
      enhancing cognition understanding and cognition expression.

PMID- 24032194
TI  - [Case of primary open-angle glaucoma].

PMID- 24032195
TI  - [Evolution on rotation manipulation].
AB  - Through review of ancient literature, the developing history of rotation
      manipulation is traced, various rotation manipulation techniques in different
      historical periods are analyzed, and evolution process of rotation manipulation
      is also summarized. It is found that uni-direction rotation was mainly adopted
      before the establishment of the Republic of China (1911). Influenced by Japanese
      technique, back and fro rotation took place of the uni-direction rotation, and
      became the mainstay of the rotation manipulations. However, it is held that the
      uni-direction rotation has stronger stimulative effects as well as soft tissue
      relaxation effect, which can be applied for treatment of various diseases.

PMID- 24032196
TI  - [Relationship between stimulus quantity and acupuncture reinforcing and reducing
      manipulations].
AB  - To make clear the concept of reinforcing and reducing manipulations of
      acupuncture, so as to better instruct the clinical practice and enhance the
      therapeutic effect. Inspired by the dispute on stimulus quantity in reinforcing
      and reducing manipulations of the modern physicians, and on the basis of Huangdi
      Neijing (Huangdi's Canon of Internal Classic), relations between stimulus
      quantity and different manipulations were explored through studies on reducing
      and reinforcing experiences of outstanding modern physicians as well as the
      related scientific re searches. Taking references of both ancient and modern
      experiences, it is held that stimulus quantity can not be taken as the only index
      to describe the reinforcing and reducing manipulations of acupuncture, there is
      no corresponding relation between them. However, it has a certain positive
      significance on instruction of clinical practice and standardization of modern
      scientific researches.

PMID- 24032197
TI  - [Discussion on twenty four moxibustion styles of Meihua acupuncture-moxibustion
      school].
AB  - Nomination, apparatus, manipulating techniques, indications and theoretical basis
      of 14 single moxibustion styles including Chuijiu (insufflating moxibustion),
      Dianjiubi Jiu (pecking moxibustion with a pen-like stool), Jiujia Xunjiu
      (moxibustion with frame), Tongmai Wenyang Jiu (moxibustion for removing meridian
      obstructions and warming up yang), QifuJiu (moxibustion on umbilicus and
      abdomen), Xiongyang Jiu (moxibustion on the chest for reinforcing yang qi),
      Toujing Jiu (moxibustion on head and neck), Anmo Jiu (moxibustion with massage),
      Zhiti Jiu (moxibustion on extremities), Guan Jiu (moxibustion with a tube), Zu
      Jiu (moxibustion on foot), Wenzhenjiu (warm needling), Huanong Jiu (festering
      moxibustion) and Gewu Jiu (indirect moxibustion) are expounded in this article.
      And 10 compound moxibustion with the combination of 2 or more than 2 above
      mentioned single moxibustion style under the instruction of combination of local
      and distal points, combination of upper and lower points as well as combination
      of frontal and back points are also stated. It suggests to classify moxibustion
      into categories of festering moxibustion and mild moxibustion, indirect
      moxibustion and direct moxibustion, and to classify moxibustion apparatus into
      the categories of treating tools and assisting tools.

PMID- 24032198
TI  - [Thirty patients on treating the acute complications of incarcerated hemorrhoid
      with acupuncture].

PMID- 24032199
TI  - [Effects of electroacupuncture at different acupoints on learning and memory
      ability and PSD-95 protein expression on hippocampus CA1 in rats with autism].
AB  - OBJECTIVE: To explore the effect mechanism of electroacupuncture (EA) at
      Changqiang (GV 1) or Baihui (GV 20) on autism based on molecular biology.
      METHODS: The autism model was established by intraperitoneal injection of sodium
      valproate (VPA) in Wistar pregnant rats. Forty young rats with autism were
      selected and randomly divided into a model group, a non-acupoint group, an
      electroacupuncture at "Changqiang" (GV 1) (EAGV 1 for short) group and an
      electroacupuncture at "Baihui" (GV 20) (EAGV 20 for short) group. Another 10
      normal young rats were selected as a blank group. In the EAGV 1 group,
      acupuncture was applied at Houhai [as Changqiang (GV 1)], then EA apparatus was
      connected with continuous wave, 2 Hz, 20 min, once a day for consecutive 20 days.
      The same EA manipulation as EAGV 1 group was used in the EAGV 20 group where
      "Baihui" (GV 20) was selected and non-acupoint group where non-acupoint in the
      right rib was selected. Blank group and model group were reared under the same
      conditions without any intervention. The escape latency and the ratio of swimming
      distance in platform quadrant to total swimming distance in each group were
      observed by using Morris water maze, and the PSD-95 protein expression in
      hippocampal CA 1 was measured by immunohistochemical techniques. RESULTS:
      Compared with the blank group, the escape latency in the model group and the non
      acupoint group lengthened (both P < 0.05), the ratio of swimming distance in
      platform quadrant to total swimming distance was decreased (both P < 0.05), the
      PSD-95 protein expression was decreased (P < 0.05). Compared with the model
      group, the escape latency in the EAGV 1 group and the EAGV 20 group were
      decreased (both P < 0.05), the ratio of swimming distance in platform quadrant to
      total swimming distance was increased, the PSD-95 protein expression was
      increased (both P < 0.05). But the escape latency, the ratio of swimming distance
      in platform quadrant to total swimming distance and the PSD-95 protein expression
      had no significant difference between EAGV 1 group and EAGV 20 group (P > 0.05).
      CONCLUSION: Electroacupuncture at Changqiang (GV 1) or Baihui (GV 20) can
      respectively improve learning and memory ability of rats with autism, which has
      no significant difference and the mechanism of action may be related to
      regulation of the PSD-95 protein expression.

PMID- 24032200
TI  - [Infantile intractable diarrhea treated with moxibustion].

PMID- 24032201
TI  - [Effects of electroacupuncture on hippocampal nNOS expression in rats of post
      traumatic stress disorder model].
AB  - OBJECTIVE: To explore the mechanism of electroacupuncture (EA) in the treatment
      of post-traumatic stress disorder (PTSD). METHODS: Thirty male Sprague-Dawley
      rats were randomly divided into a normal group, a model group and an
      electroacupuncture group. The single prolonged stress (SPS) method was used to
      set up the PTSD models in latter two groups. After SPS Stimulation, EA group was
      treated with 2Hz electroacupuncture at Baihui (GV 20) and Zusanli (ST 36) for 30
      min, once a day for a week. Reverse transcriptase polymerase chain reaction (RT
      PCR) and immuno-histochemistry were used to detect the mRNA and protein
      expression of nNOS in the hippocampus of rats in the each group. RESULTS: (1) The
      nNOS mRNA expression in hippocampus in model group was higher than that in normal
      group (P < 0.05). But the expression in EA group was lower significantly than
      that in model group (P < 0.05). (2) The nNOS protein expression in hippocampus
      CA1 and CA3 in model group was higher than that in normal group (P < 0.05). But
      after electroacupuncture treatment, its expression in EA group was lower
      significantly than that in model group (P < 0.05). The nNOS protein expression in
      hippocampal CA2 had no difference among all three groups. CONCLUSION: The
      elevated nNOS expression in hippocampus may be involved in the pathological
      process of PTSD. Electroacupuncture play a down-regulation effects in the
      hippocampal nNOS expression, which may be one mechanism of electroacupuncture for
      treatment of PTSD.

PMID- 24032202
TI  - [Professor CHEN Quan-xin's experience for treatment of insomnia: regulating
      spirit and quieting heart to help sleep].
AB  - This article describes the experiences of professor CHEN Quan-xin, an old famous
      TCM doctor, in the treatment of insomnia. He believes that insomnia stems from
      incoordination between nutrient qi and defensive qi and deficient cultivation of
      cardiac spirit, and treatment of insomnia need to regulate spirit and quiet heart
      coherently. Painless acupuncture method of Chen's flying needling is adopted
      including to select Shenmen (HT 7), Sanyinjiao (SP 6) and Anmian (Extra) as the
      main points and take special needling technique and grading reinforcing and
      reducing manipulations. During treatment, he pays attention to understanding
      patients' psychological and mental status through "watching one's expressions and
      weighing his words carefully".

PMID- 24032203
TI  - [Clinical application of the penetrating needling technique from neiguan (PC 6)
      to waiguan (TE 5) by Professor LIU Kong-teng].
AB  - The clinical experience of Professor LIU Kong-teng's needling techniques and
      methods of the penetrating needling from Neiguan (PC 6) to Waiguan (TE 5) in the
      treatment of various diseases is introduced in this paper. The acupoints
      characteristics, penetrating needling techniques and methods and the clinical
      indications are summarized. Examples of Elbow flaccid paralysis, headache,
      insomnia, neck contracture, vomiting, hiccups, heart disease, the acute abdominal
      pain, acute lumbar sprain, acute ankle joint sprain and periarthritis of shoulder
      are given to explain techniques and methods of the penetrating acupuncture.

PMID- 24032204
TI  - [Clinical experiences of RUAN's needling method for insomnia].
AB  - The theoretical basis and needling techniques of RUAN's needling method in
      treatment of insomnia are introduced in this paper. Ruan's needling method
      follows the theory of traditional Chinese medicine and acupuncture, stresses the
      theory of taking brain as the marrow sea in treatment of insomnia acupuncture.
      The characteristics of his needling method are that emphasis on acupoints,
      including positioning accuracy and proper compatibility; think highly of needling
      method that combines with perpendicular needling, oblique needling, parallel
      needling, deep needling and shallow needling; emphasis on manipulation and
      identify qi under the needle to decide reinforcing or reducing method by arrival
      of qi, excess or deficiency. And the clinical observation of RUAN' s needling
      method on 30 cases of insomnia is attached.

PMID- 24032205
TI  - [Effect of assisted anesthesia of auricular point magnetic sticking on
      postoperative recovery of gynecological surgery].
AB  - OBJECTIVE: To explore an optimum method on postoperative recovery of general
      anesthesia gynecological laparoscopic surgery. METHODS: One hundred and twenty
      cases of gynecological laparoscopic surgery were randomly divided into three
      groups, 40 cases in each one. The sensitive points of bilateral Shenmen (TF4),
      Zigong (TF2), Wei (CO4), Dachang (CO7) and so on were selected in all three
      groups one night before the surgery. The sticking with magnetic beads was applied
      in the group A. The magnetic beads were in-pair stuck at front-back corresponding
      location of both ears in the group B. The same-appearance plaster was put at the
      corresponding acupoints in the group C. The intubation anesthesia was applied in
      all three groups and postoperative recovery of gynecological laparoscopic surgery
      was observed. RESULTS: The postoperative visual analogue scale (VAS) was (1.77 +/
      1.65) in the group A and (1.80 +/- 1.96) in the group B, which was both lower
      than (2.62 +/- 1.46) in the group C (both P < 0.01). The occurrence rate of
      nausea and vomiting was 25.0% (9/36) in the group A and 20.0% (8/40) in the group
      B, which was both lower than 50.0% (19/38) in the group C (both P < 0.01). The
      recovery of borborygmus on postoperative 1st and 3rd day in the group A and B was
      faster than that in the group C (both P < 0.05), while time of fart and
      defecation in the group A and B was earlier than that in the group C (both P <
      0.05). The score of state-trait anxiety inventory in the group A and B was lower
      than that in the group C (both P < 0.05), but the differences of each item
      between the group A and B were not obvious (both P > 0.05). CONCLUSION: The
      auricular point sticking could support analgesia of general-anesthesia
      gynecological laparoscopic surgery, which could relieve anxiety mood, reduce
      occurrence of nausea and vomiting and improve function of stomach and intestine
      to benefit postoperative recovery. However, the effect of in-pair sticking of
      auricular point with magnetic beads at front-back acupoints was not obviously
      strengthened.

PMID- 24032206
TI  - [Case of heatstroke sequelae].

PMID- 24032207
TI  - [Thinking on research of acupuncture for amblyopia].
AB  - It has been found by the author that among the researches concerning acupuncture
      in the treatment of amblyopia, only anisometropic amblyopia has noticeable
      results with treatment. Based on the previous publications, a hypothesis theory
      of self biological single eye occlusion is displayed particularly for simplex
      anisometropic amblyopia. It is also reminded that amblyopia acupuncture treatment
      does not always have sufficient RCTs for clinical research, so it couldn't be
      promoted as a normalized clinic treatment measure on an international base. It is
      also mentioned that reports from mainland China present a significant discrepancy
      with that from international in terms of successful treatment percentage. This is
      probably caused by the disagreement of amblyopia test methods and clinical
      standards. Some important considerations and key points that require particular
      attention during amblyopia acupuncture treatment and several recommendations on
      development and directions for further research are also put forward.

PMID- 24032208
TI  - [Application of associated symptom and sign-based acupoint selection in
      acupuncture-moxibustion treatment].
AB  - Based on traditional acupuncture-moxibustion treatment ideas, with
      differentiation of channels and collaterals as main part and feature, the
      important role of associated symptom and sign-based acupoint selection in
      acupuncture-moxibustion treatment is explained from angles of philosophy and
      medicine. Combined with clinical experience of acupuncture and moxibustion, the
      category of associated symptom and sign-based acupoint selection is explained in
      detail to make sure the accuracy of acupuncture-moxibustion differentiation. It
      could show uniqueness and advantage of theory and clinic in acupuncture
      moxibustion and provide theoretical references in making acupuncture-moxibustion
      prescription to improve effectiveness of clinical treatment.

PMID- 24032209
TI  - [Acupuncture on conception vessel combined with auricular point sticking for 63
      cases of insomnia].

PMID- 24032210
TI  - [Case report on adverse reaction of acupoint catgut embedding].

PMID- 24032211
TI  - [The manipulation technique and clinical application of kinetic cupping].
AB  - The characteristic of kinetic cupping is explained from treatment principles,
      manipulation and clinical application. The kinetic cupping is a new particular
      therapy that combines traditional cupping and kinetic therapy. With cups on the
      patient, limb action like flexion-extension, adduction-abduction and rotation is
      made to reinforce clinical effects, which has simple and safe manipulation,
      obvious efficacy and is well accepted by patient. It has more obvious advantage
      for pain that was caused by large-area soft tissue injury and discomfort where
      acupuncture is not appropriate.

PMID- 24032212
TI  - [Discussion on the regular of acupoint selection of acupuncture and moxibustion
      for lumbar disc herniation during recent 10 years].
AB  - By taking "lumbar disc herniation", Chinese medicine", "acupuncture and
      moxibustion" as key words Chinese articles about acupuncture for lumbar disc
      herniation in recent 10 years were searched in three major Chinese databases of
      Wan fang database, VIP database and CNKI. Totally 546 relative articles were
      retrieved. After the elimination of invalid articles, 173 were included as valid
      articles with 49 main acupoints. The hierarchical clustering statistical method
      was used to analyze the possible rules among the former 20 acupoints. It turned
      out that there were 10 most common used acupoints on Bladder Meridian [Geshu (BL
      17), Xiaochangshu (BL 27), Shenshu (BL 23), Dachangshu (BL 25), Pangguangshu (BL
      28), Guanyuanshu (BL 26), Weizbong (BL 40), Zhibian (BL 54), Chengshan (BL 57),
      Kunlun (BL 60)], 2 on Gallbladder Meridian [Huantiao (GB 30), Yanglingquan (GB
      34)], 2 on Governor Vessel [Yaoyangguan (GV 3), Shuigou (GV 26)], 2 on Stomach
      Meridian [Zusanli (ST 36), Juliao (ST 3)], 2 on Spleen Meridian [Sanyinjiao (SP
      6), Xuehai (SP 10)], and the rest were extra points (Huatuo Jiaji) and Ashi
      points, so a conclusion could be drawn that the most common used acupoints were
      Bladder Meridian acupoints and supplemented by Gallbladder Meridian, Governor
      Vessel, Stomach Meridian, Spleen Meridian, extra points and Ashi points. The
      selected acupoints were most located on the lumbosacral region, leg and fewer
      located on the face, back and local part.

PMID- 24032213
TI  - [Russian Research Center of Radiology and Surgical Technologies of the Ministry
      of Health of Russia--95th anniversary. Past, present and future perspectives].

PMID- 24032214
TI  - [Possibilities of using molecular imaging methods with complex modern
      radiopharmaceuticals in neurooncology].

PMID- 24032215
TI  - [Arterial radioembolization of malignant liver tumors by yttrium-90
      microspheres].

PMID- 24032216
TI  - [Pathophysiological rationale of the efficacy of conservative non-pharmacological
      therapy for urinary incontinence after radical prostatectomy].

PMID- 24032217
TI  - [The cellular microenvironment of malignant tumors and its significance in their
      prognosis].

PMID- 24032218
TI  - [Predicting the effectiveness of experimental radiation therapy for gliomas with
      the administration of iron ions].

PMID- 24032219
TI  - [First experience of using positron emission tomography with 11C-choline in
      prostate cancer (PC)].
AB  - Introduction into clinical practice of combined positron emission technology and
      computer tomography (PET/CT) allows in one study to identify structural and
      functional abnormalities. The study involves 32 patients who underwent PET/CT
      with "C-choline, including 5 patients with prostate cancer (PC), 3--with chronic
      prostatitis and 24--with biochemical PC recurrence. PET/CT with 11C-choline has a
      high diagnostic efficacy in detection of local recurrence and PC metastases in
      patients with biochemical PC recurrence. The results of visual analysis do not
      permit to distinguish PC from benign prostate diseases.

PMID- 24032221
TI  - [Predictive value of positron emission tomography with 18F-FDG in the diagnosis
      and staging of patients with Hodgkin's lymphoma].
AB  - Eighty nine patients with newly diagnosed Hodgkin's lymphoma (HL) underwent
      conventional staging methods including computer tomography (CT) as well as
      positron emission tomography (PET) with 18F-FDG. All lesions in PET with 18F-FDG
      and CT were correlated to each other. Identical results of PET and CT in
      identifying pathological focuses were obtained in 220 anatomical regions.
      Discordant results of PET and CT were determined in 59 anatomical areas. In 27
      cases data of both methods were equivocal and could be regarded as normal or
      pathological. Analysis of the results showed the sensitivity, specificity and
      diagnostic accuracy of PET were higher than the diagnostic efficacy of CT in the
      detection of pathological lymph nodes, extranodal organs as well as in
      localization of disease above and below diaphragm. The sensitivity of CT was
      lower in the detection of pathological lymph node and extranodal organs below the
      diaphragm--68.5%. In accordance with the results of PET the stage of disease and
      treatment tactics were changed 11.2% patients.

PMID- 24032220
TI  - [The results of proton radiosurgery for pituitary endosellar adenomas].
AB  - 465 patients with pituitary endosellar adenomas have passed irradiation on the
      synchrocyclotron PNPI (1000 MeV). Due to the high energy of the proton beam the
      rotating-convergent shoot-through technique was used. The single dose of 80-100
      Gy was given. In patients with prolactin adenomas clinical remission was detected
      in 80%, and the stabilization of the disease was achieved in 15%. Pregnancies in
      21 patients ended in the birth of healthy children, and 4 of them gave the birth
      twice. Complete clinical remission was observed in 92% of patients with Cushing's
      disease. Sustained recovery and full normalization of growth hormone level were
      observed during long-term follow-up in 86% of patients with acromegaly. There was
      significant reducing of the high hormone level on the fifth year of follow-up in
      any clinical form of pituitary adenomas while the development of the secondary
      hypopituitarism was not defected in the most of the patients. Clinical remission
      in patients with non-secreting adenomas was 95%. Irradiation by the proton beam
      was not accompanied by serious life-threatening complications. Thus this type of
      treatment for pituitary endosellar adenomas is highly effective and safe and,
      sometimes, the only method.

PMID- 24032222
TI  - [The mechanism of the antitumor effect of total/subtotal radiotherapy with non
      tumoricidal doses of radiation].
AB  - The myelodepression at therapy for solid malignancies is considered as a
      mediating element of common antineoplastic activity on the basis of ability of
      stem cells of hemapoietic system to participate in regeneration of the various
      tissues of the body, including tumor. The equivalence of the therapeutic benefit
      mediated by both mild myelodepression due to total/subtotal radiation exposure
      and conventional chemotherapy with cytotoxic drugs is argued.

PMID- 24032223
TI  - [Assessment of the therapeutic possibilities of systemic radiotherapy as a
      component of combined treatment for advanced ovarian carcinoma].
AB  - The new technology of combined treatment for patients with ovarian carcinoma of
      III-IV stages and its relapse is presented. The essentially new component is
      systemic radiotherapy in nontumoricidal doses. It is used with both traditional
      surgical and chemotherapeutic components. Systemic radiotherapy is carried out in
      a form of subtotal body irradiation in two dose-time options with total dose of 1
      Gy and 9 Gy. The choice of radiation option is carried out taking into account
      the initial somatic resource of patients estimated by the condition of
      lymphopoiesis. The use of systemic radiotherapy in combined treatment of advanced
      ovarian carcinoma allowed to achieve the significant increase of 3-, 5-year
      survival in patients as compared to traditional chemo-surgical method. Indirect
      mechanism of nontumoricidal systemic radiotherapy is to be considered as a vital
      way for tumor control.

PMID- 24032224
TI  - [Comparative evaluation of the predictive value of UroVysion and AURKA FISH tests
      of urine sediment cells for the diagnosis of bladder cancer].
AB  - Informative value of two tests based on FISH of exfoliated urothelial cells in
      urine sediment (AURKA and UroVysion) was compared in the group of patients (31
      persons) with the history of bladder cancer. Coincidence in results of both FISH
      assays was found in 93.5%. These preliminary data offer the possibility of
      replacing the expensive UroVysion kit by the less expensive AURKA FISH probe and
      it could be used for monitoring of recurrence in bladder cancer patients.

PMID- 24032225
TI  - [Preliminary experience with assessing the motor pathways and central inhibition
      in patients with malignant cerebral gliomas in preparation for conformal
      radiotherapy].
AB  - We investigated central motor pathways and central inhibition in patients with
      brain gliomas by transcranial magnetic stimulation (TMS). 10 glioma patients and
      16 matching controls were enrolled. Central motor conduction time, MEP latencies
      and amplitudes and silent period were evaluated. In 90% glioma patients TMS
      parameters were abnormal, mostly MEP shapes and thresholds were affected. In 40%
      of the cases central inhibition in glioma affected hemisphere was abnormally
      high. We propose that TMS is safe and informative tool in glioma patients;
      central inhibition seems to be affected in some cases by the glioma presence in
      the hemisphere. One of the possible causes of that may be GABA system activation.

PMID- 24032226
TI  - [Effectiveness of combined systemic and regional chemotherapy in treating
      patients with metastatic colorectal cancer after extrahepatic progression of the
      disease].
AB  - There was conducted an assessment of the effectiveness of a combination of
      systemic and regional modes of chemotherapy versus systemic chemoinfusion in
      treatment of 70 patients with unresectable metastases of colorectal cancer in the
      liver after extrahepatic progression of a disease. The use of combined therapy
      statistically significantly increased overall survival more than doubled as
      compared to a group of systemic chemotherapy (median 10 vs. 4.5 months, p =
      0.002) as well as the time before intrahepatic progression (median 5.9 vs. 3.5
      months, p = 0.01). In addition, there was a trend toward a greater frequency of
      objective responses in the combination therapy group 18% in comparison with 9.7%
      in the systemic chemotherapy group (p = 0.49) but the difference was not
      statistically significant and it needed further study on more clinical material.

PMID- 24032227
TI  - [A comparative study of the myeloprotective effect of dicarbamine and leucostim
      in experimental post-radiation bone marrow syndrome].
AB  - We studied the effect of dicarbamine and leucostim on myelopoiesis in
      experimental post-radiation bone marrow syndrome. Dicarbamine in different modes
      of administration and doses provided a high level of protection of proliferating
      hematopoietic precursors in the early period after radiation, which was reflected
      in a statistically significant decrease in the depth and duration of post
      radiation deficit of cells, such as of granulocytes, lymphocytes, megakaryocytes
      and erythroid cells. The greatest effect of the drug appeared at a dose of 4
      mg/kg (prophylactic administration) and a dose of 15 mg/kg (curative double
      dose). In the bone marrow of experimental animals leucostim prevented development
      of post-radiation deficit of granulocytes and lymphocytes to a lesser extent,
      than dicarbamine, and it was effective for erythroid cells and megakaryocytes.

PMID- 24032228
TI  - [Sensitivity of PET with 18F-fluorodesoxyglucose in the diagnosis of
      neuroendocrine tumors of the lungs].
AB  - PET with 18F-FDG was administered to 46 patients with different morphological
      types of neuroendocrine tumors. The method appeared to be highly sensitive in the
      diagnosis of atypical carcinoids as well as neuroendocrine large-cell lung cancer
      and small-cell lung cancer. At the same time its imaging capabilities in the
      detection of typical carcinoids were limited. The sensitivity of PET in these
      patients was 66.7%. However, the absence of 18F-FDG hyperfixation in typical
      carcinoids had strong evidence in favor of conditional benign process.

PMID- 24032230
TI  - [Patients' evaluation of the quality of specialized care to cancer patients at
      the Russian Research Center of Radiology and Surgical Technologies (RRCRST)].
AB  - Questioning of 416 patients established that level of satisfaction of patients,
      treated at RRCRST, by all components of quality of medical care is rather high.
      The main reasons for dissatisfaction were the sanitary condition of the wards and
      common areas, the quality of food and clothes, the attitude of nurses.

PMID- 24032229
TI  - [Current technologies in radiotherapy for non-Hodgkin lymphomas].
AB  - The clinical observations of 207 patients with non-Hodgkin's lymphomas, treated
      with radiotherapy and chemoradiotherapy at our institution in 1999-2012 years,
      were presented. 136 patients had the extranodal lymphomas, 40 patients had plasma
      cell tumors and 31 patients had follicular lymphoma. Complete regression of the
      lesions was observed in all 24 patients with a local lesion of the skin, an
      objective response of a variable degree was received in all 27 patients with
      generalized disease within skin. The radiation therapy of the stomach and
      perigastric lymph nodes led to complete remission in 100% cases. Conformal
      radiotherapy with 3D-planning in patients with a primary lesion of the orbit
      avoided irradiation of the intact eye. The 3 Gy fractionation mode was more
      effective in the treatment of myeloma and solitary plasmacytoma of bone, whereas
      the standard fractionation mode was more effective in patients with extraosseous
      plasmacytoma. Radiation therapy of follicular lymphoma has showed consistent
      results, which demonstrated by 100% of 5-year tumor-specific survival in the
      whole group, 100% disease-free survival in patients with stage II, the lack of
      recurrence in the irradiation fields.

PMID- 24032231
TI  - [Effectiveness of the correction of hepatotoxicity during combined
      chemoradiotherapy for cancer patients].
AB  - In 29 patients with various malignant tumors there was carried out an estimation
      of Thiotriazoline efficacy in the treatment of hepatotoxicity in the process of
      combined chemoradiation therapy. It has been showed that ten-day application of
      Thiotriazoline in double dose (2,5% solution intravenously by 4,0 ml twice within
      24 hours and 1 tablet (100 mg) twice within 24 hours) in patients with I and II
      degree of hepatotoxicity at the background of combined chemoradiation therapy
      enabled to remove completely manifestations of cytolysis in 100% of patients,
      without changing regimen of chemotherapy. To normalize levels of biochemical
      indices of blood in III degree of hepatotoxicity, more a long intake of
      Thiotriazoline (about 4 weeks) was required. Regimen of chemoradiation therapy in
      the period of Thiotriazoline application was not changed.

PMID- 24032232
TI  - [Use of hydrogel tissues with 5-fluorouracil and sodium alginate, "COLETEX-5
      FTUR," for radiomodification in cancer patients receiving radiation therapy].
AB  - Radiomodification is one of the most available and repeatable methods of
      amplification of the tumor damage in radiotherapy. The application of 5 FU
      hydrogel tissues for colorectal and breast cancer patients enables to complete
      the surgery, increase performance of radiation treatment, reduce the relapse
      frequency.

PMID- 24032233
TI  - The future of health care's past.

PMID- 24032234
TI  - Nurses across borders: displaced Russian and Soviet nurses after World War I and
      World War II.
AB  - Russian and Soviet nurse refugees faced myriad challenges attempting to become
      registered nurses in North America and elsewhere after the World War II. By
      drawing primarily on International Council of Nurses refugee files, a picture can
      be pieced together of the fate that befell many of those women who left Russia
      and later the Soviet Union because of revolution and war in the years after 1917.
      The history of first (after World War I) and second (after World War II) wave
      emigre nurses, integrated into the broader historical narrative, reveals that
      professional identity was just as important to these women as national identity.
      This became especially so after World War II, when Russian and Soviet refugee
      nurses resettled in the West. Individual accounts become interwoven on an
      international canvas that brings together a wide range of personal experiences
      from women based in Russia, the Soviet Union, China, Yugoslavia, Canada, the
      United States, and elsewhere. The commonality of experience among Russian nurses
      as they attempted to establish their professional identities highlights, through
      the prism of Russia, the importance of the history of the displaced nurse
      experience in the wider context of international migration history.

PMID- 24032235
TI  - "Coming to grips with the nursing question": the politics of nursing education
      reform in 1960s America.
AB  - The 1950s and 1960s were decades of change for the American nursing profession. A
      new generation of nurse educators sought to create greater professional autonomy
      for the nurse by introducing new models of education that emphasized science
      based learning over technical skills and bedside care, and creating new clinical
      roles for the nurse, based on advanced graduate education. They confronted
      resistance from an older generation of nurses who feared becoming "second-class
      citizens" in increasingly academic nursing schools, and from academic health care
      institutions all too comfortable with the gendered hierarchy on which the
      traditional model of nursing education and practice was predicated. Using the
      University of Minnesota and University of California-Los Angeles (UCLA) as case
      studies, and based on institutional records and more than 40 oral histories with
      nursing and medical faculty, this article describes the generational conflicts
      this new cadre of nurse educators confronted within schools of nursing, and the
      institutional politics they struggled with as they sought to secure greater
      institutional status for the schools among the universities' other health science
      units.

PMID- 24032236
TI  - "It's been a long road to acceptance": midwives in Rhode Island, 1970-2000.
AB  - A resurgence of midwifery came to Rhode Island in the 1970s. Midwives acted as
      modern health care professionals to conserve a traditional woman-centered birth,
      but the battle was long and arduous, from Dr. Ellen Stone attempting to eliminate
      midwives in the state in 1912 to doctors using the death of 2 home birth infants
      in the 1980s to undermine the growing presence of professional nurse-midwives in
      the state. Midwives prevailed when the state legislature passed measures in 1988
      and 1990 increasing the power and authority of midwives, and when a federal grant
      in 1993 allowed the University of Rhode Island to open the first training program
      for nurse-midwives in the state.

PMID- 24032237
TI  - Setting the stage.

PMID- 24032238
TI  - Boundary crossings in the history of health care.

PMID- 24032239
TI  - Tiptoeing towards a history of nursing in Europe.

PMID- 24032240
TI  - International nursing history: the International Council of Nurses history
      collective and beyond.

PMID- 24032241
TI  - History and nursing history at Penn in the 1980s.

PMID- 24032242
TI  - Inspiration and guidance.

PMID- 24032243
TI  - A graduate's gratitude.

PMID- 24032244
TI  - Joan Lynaugh.

PMID- 24032245
TI  - Reflections on a legacy of mentorship.

PMID- 24032246
TI  - Edward L. Bernays and nursing's code of ethics: an unexplored history.

PMID- 24032247
TI  - A colleague's salute to Joan Lynaugh.

PMID- 24032248
TI  - Transnational feminist practices and the history of nursing.

PMID- 24032249
TI  - A salute to Rosemary Theresa McCarthy, RN, PhD, FAAN, Colonel U.S. Army
      (retired).

PMID- 24032251
TI  - July 1.

PMID- 24032250
TI  - Eleanor Krohn Herrmann, February 1, 1935-July 31, 2012: excerpts from a eulogy by
      Lawrence Herrmann.

PMID- 24032252
TI  - "Feelings change facts".

PMID- 24032253
TI  - Evaluating quality of care: the role of peer review.
AB  - Peer review for quality of care is often conducted to address issues such as
      professional staff conflict, hospital or clinic privileging, identified quality
      concerns or patient complaints, and group practice membership decisions. Inherent
      to the definition of peer review is independent and unbiased review of the
      quality of care by a person or persons in the same profession who are of the same
      or higher ranking or training. While many studies have outlined the limitations
      of the peer review process, the reliability of the process can be improved by
      providing more structured assessments to identify differences in patient
      management, adjusting systematic bias resulting from the individual reviewer and
      their professional background, summarizing assessments from multiple independent
      reviewers, and using structured implicit review based on evidence-based
      guidelines or performance metrics. Active participation in the process by
      practicing physicians and healthcare professionals is essential for the success
      of effective peer review.

PMID- 24032255
TI  - Oklahoma Health Care Authority's (OHCA) Drug Utilization Review (DUR) Board.

PMID- 24032254
TI  - Do adults with a diagnosis of type II diabetes mellitus without cardiac symptoms
      who undergo routine cardiac stress testing suffer fewer first time episodes of
      myocardial infarction than those who do not undergo routine cardiac stress
      testing?

PMID- 24032256
TI  - In patients with chronic diabetic nephropathy, do angiotensin-converting enzyme
      inhibitors (ACEI) have greater renal protective effect as compared to angiotensin
      receptor blockers (ARB)?

PMID- 24032257
TI  - [Transabdominal chorionic villus sampling (CVS) for prenatal diagnosis of
      chromosomal disorders--own experiences].
AB  - OBJECTIVE: To present the authors' own experiences on transabdominal Chorionic
      Villus Sampling (CVS) for prenatal diagnosis of genetic disorders. DESIGN:
      Descriptive study PATIENS AND METHODS: A total of 290 couples with request for
      prenatal diagnosis of various genetic disorders were studied. The most common
      indications were: fetal abnormalities suspected in an ultrasound scan and
      biochemistry positive family history on genetic disorders, maternal age.
      Transabdominal CVS was done under local anesthesia and ultrasound guidance. The
      genetic analysis was possible in 264 cases (241 with abnormal ultrasound scan
      and/or biochemistry 11 with positive family history 12 with maternal age).
      Results were recorded and analyzed for descriptive statistics. RESULT: A total of
      290 CVSs were done in the outdoor Most procedures (76%) were done between 12 and
      14 weeks (range 11-16 weeks). All placental positions including both anterior and
      posterior were approachable through the trans-abdominal route. The overall
      success rate was 100%. Abnormal fetal karyotype was diagnosed in 39% of cases. In
      12.9% of cases inconclusive results were observed (due to placental mosaicism or
      maternal cells contamination). More aneuploidies were observed in group with
      abnormal first trimester screening (us scan and/or biochemistry) compared to any
      other indications. CONCLUSION: Transabdominal CVS is a useful outdoor procedure
      for prenatal diagnosis. However indications for the procedure should be carefully
      considered since some risk of inconclusive results occurred.

PMID- 24032258
TI  - Evolution of the indications for genetic amniocentesis after the introduction of
      the prenatal screening program by the national health insurance in Poland.
AB  - OBJECTIVE: In 2008, the Prenatal Screening Program was introduced by the National
      Health Insurance in the Pomeranian region of Poland. As of then, biochemical and
      ultrasound screening was offered to women eligible for amniocentesis according to
      the earlier policy. The aim of the study was to investigate the evolution of the
      indications for amniocentesis after the introduction of the Program. MATERIAL AND
      METHODS: In total, 2579 women referred for amniocentesis to the Department of
      Obstetrics, Medical University of Gdansk, were included in the study They were
      divided into two groups: 1705 women referred between 1996 and 2007 (group A) and
      874 women referred between 2008 and 2010 (group B). Indications for amniocentesis
      were compared between the groups. RESULTS: A significant difference in the
      indications for amniocentesis was found between the groups (Kruskal-Wallis test;
      p < 0.001). Maternal age, fetal malformation in the previous pregnancy and
      anxiety were less frequent in group B (p < 0.0001, p = 0.0008 and p = 0.0156,
      respectively). In contrast, a higher frequency of positive biochemical screening
      and abnormal ultrasound results as indications for amniocentesis was found in
      group B (p < 0.0001 and p = 0.0008, respectively). CONCLUSIONS: The introduction
      of the Prenatal Screening Program by the National Health Insurance shifted the
      proportion of indications for amniocentesis from maternal age to positive results
      in biochemical and ultrasound screenings, and increased the number of invasive
      testing. Further observation of the trend and its influence on the detection rate
      is imperative to confirm that the proposed Program is adequate and does not
      require adjustments.

PMID- 24032259
TI  - [Risk estimation of different pregnancy outcomes in the families of carriers of
      reciprocal chromosomal translocations involving chromosome 20].
AB  - Carriership of reciprocal chromosome translocation (RCT) in a family may be the
      reason for malformation at birth, stillbirth, early neonatal death, and
      miscarriage due to unbalanced karyotype (monosomy/trisomy). The size of
      chromosome segments determined by the breakpoint position, kind of chromosome
      involved and the carrier gender may influence the probability rate for each
      category of the unfavorable pregnancy outcome in the family of the carrier of a
      particular RCT Until now, the literature lacks reports on the risk values for
      particular forms of pregnancy outcomes in case of single segment imbalance, both
      the short (p) and the long arm (q) of chromosome 20. OBJECTIVE: The aim of the
      study was to evaluate individual risk rates for unbalanced offspring at birth for
      single segment imbalance in the form of trisomy/monosomy and a separate
      evaluation risk figures for different pregnancy outcomes, depending on the size
      of the involved chromosome segment, its origin and carrier gender in families of
      RCT carriers involving chromosome 20 (RCT-20). In addition, practical application
      of the obtained results in the family with unique RCT t(13;20)(q14.1;p11.21)
      carriership has been shown. MATERIAL AND METHODS: Total empirical data of 50
      families (219 pregnancies) were collected from 19 pedigrees of RCT-20 carriers
      coming from different collections of RCT and available references. Cytogenetic
      studies were performed by GTG technique. The probability rates of particular type
      of pathology related to the total number of pregnancies after ascertainment
      correction have been done by segregation analysis according to the method of
      Stengel-Rutkowski and Stene. RESULTS: The probability rate for unbalanced
      offspring at birth for carriers of RCT-20p was calculated as 5.5 +/- 1.8% (9/164)
      (medium risk). Considering parental gender of the carrier for maternal (MAT) and
      paternal (PAT) carriers, the probability rate values were similar i.e. 4.8 +/-
      2.3% (4/84) and 4.9 +/- 2.8% (3/61), respectively. The risk figures for
      stillbirth/early neonatal deaths were found as 0.6 +/- 0.6% (1/164) (low risk),
      but separately for MAT and PAT carriers they were: 1.2 +/- 1.2% (1/84) and < 0.8%
      (-/61), respectively. Risk figures for miscarriages were estimated as 28.6 +/-
      3.5% (47/164) (high risk), with 32.1 +/- 5.1% (27/84) for maternal carriers and
      32.7 +/- 6% (20/61) for paternal carriers. The risk figures for unbalanced
      offspring at birth for carriers of RCT-20q were calculated as about 2.6% (0/20)
      (low risk), for stillbirth/early neonatal death about 2.6% (-/20) (low risk) and
      for miscarriage 50 +/- 11.2% (10/20) (high risk). CONCLUSIONS: 1. The probability
      rates for unbalanced offspring at birth and for different categories of
      unfavorable outcomes show differences depending on the origin and the size of
      chromosome 20 segment. 2. There are no differences in the value of risk figures
      for particular form of pregnancy pathology in relation to carrier's gender.

PMID- 24032260
TI  - Iatrogenic and spontaneous late preterm twins--which are at higher risk of
      neonatal complications?
AB  - OBJECTIVES: To evaluate data regarding neonatal mortality and short term
      morbidity among iatrogenic late preterm (ILP) and spontaneous late preterm (SLP)
      twin births, and to estimate whether medical interventions - induction of labor
      in this particular context, are associated with better or poorer outcomes.
      MATERIAL AND METHODS: Retrospective analysis of 110 late preterm dichorionic twin
      pregnancies was performed basing on medical charts data. All twins were delivered
      in years 2005-2011 at the 1st Department of Obstetrics and Gynecology Medical
      University of Warsaw Late preterm twins, defined as those delivered between 34 +
      0-36+ 6 weeks of gestation, were divided into spontaneous and iatrogenic preterm
      births. The primary outcomes of the study were various neonatal adverse events,
      including one of the following per pregnancy: admission to Neonatal Intensive
      Care Unit (NICU), respiratory disorders (RD) and pneumonia, intraventricular
      hemorrhage (IVH), sepsis, NEC and jaundice requiring phototherapy Mann-Whitney U
      test and chi-squared test were used and logistic regression performed to
      calculate odds ratio, with p value < 0.05 considered significant. RESULTS: There
      were 69 (62.7%) spontaneous and 41 (37.3%) iatrogenic late preterm twins. There
      were no differences in maternal characteristics, mode of delivery and newborns'
      Apgar scores. The mean birth weight did not differ significantly between the
      groups. There was one case of perinatal death of one twin in ILP group.
      Preeclampsia (31.7%) and IUGR (17%) were the most frequent indications for labor
      induction in ILR Women in the ILP group were administered steroid treatment for
      lung maturation more frequently than SLP group due to pregnancy complications
      (73.17% vs. 30.44%; p < 0.0001). Nevertheless, ILP twins were at higher risk of
      respiratory disorders (41.46% vs. 15.94%; p = 0.003--significant either with or
      without pneumonia) and NICU admission (31.71% vs. 14.49%; p = 0.032) than SLP
      twins. The only two independent factors influencing the occurrence of poor
      neonatal outcome were gestational age in weeks (OR 0.57; 95% Cl 0.34-0.94) and
      preeclampsia (OR 5.01; 95% CI 1.51-16.67). In the additional analysis of
      gestational age odds ratio, only the delivery at 34 weeks of gestation increased
      the incidence of adverse neonatal outcome almost five times (OR 4.94, 95% Cl:
      1.64-14.88). The rate of cesarean delivery in the SLP was 81.61%, while in the
      ILP it reached 90.23% (p = 0.17). CONCLUSIONS: Late prematurity in twin
      pregnancies is associated with higher risk of neonatal morbidity than in term
      twins. Iatrogenic late preterm birth increases the risk of NICU admission and
      respiratory disorders in neonates in comparison to spontaneous late preterm
      birth. Despite the fact that respiratory complications are generally mild and
      mostly temporary there is a need for careful evaluation of indications for
      delivery in that particular group.

PMID- 24032261
TI  - [Prenatal MRI as a method of controlling fetal pathology].
AB  - BACKGROUND: It has been shown that MRI offers the possibility of more detailed
      assessment of fetal pathology than sonography. It is used not only to diagnose
      but also to follow up some prenatal diseases. It is a basis of in utero treatment
      and the tool of monitoring its efficacy The purpose of the study was to present
      the authors' experience with prenatal MRI as a method of follow-up of fetal
      pathology and of monitoring invasive fetal therapy MATERIAL AND METHODS: The
      study group consisted of 31 fetuses that underwent two MRI examinations. The
      first exams were performed at the gestational age of 19-28 weeks (mean: 23.6
      weeks), the follow-up between week 20 and 37 (mean: 30.5). The MRI examinations
      were performed using 1.5 T scanners. SSFSE/T2-weighted images, TSE/ or GRE/T1
      weighted images, DWI, FIESTA, EPIGRE were performed. RESULTS: In 5 cases MRI
      allowed to exclude a suspected pathology: brain anomaly in a healthy fetus, septo
      optic dysplasia in a healthy fetus, right-sided CDH in case of a left-sided
      pathology pentalogy of Cantrell, lack of bladder in a fetus with a small, thick
      walled bladder In 4 cases an additional pathology was detected on MRI: CCAM/
      pulmonary sequestration with self-regression, cerebellar hypoplasia,
      rhombencephalosynapsis, tethered cord with syringohydromyelia. In 4 cases MRI was
      used just to follow-up and showed evolution of the disease in 2 cases: regression
      of intracerebral hemorrhage, progression of kidney disease. Finally, in 18 cases
      MRI was performed before and after an open fetal surgery of myelomeningocele
      showing good outcome in 10 cases and a wide spectrum of complications in 8
      neonates: from edema of the transplant only in 4 to recurrent MC in 1.
      CONCLUSIONS: Maternal uterus constitutes a natural "incubator" for the fetus--it
      is easier and safer to perform diagnostic procedure in utero than in a seriously
      ill newborn. MRI is a method of choice in the diagnosis and of follow-up in cases
      of open fetal surgery.

PMID- 24032262
TI  - [The value of Ki-67 antigen expression in tissue microarray method in prediction
      prognosis of patients with endometrioid endometrial cancer].
AB  - OBJECTIVES: To assess the prognostic significance of Ki-67 expression in the
      tissue microarray method (TMA) for disease free survival (DFS) and overall
      survival (OS) in endometrioid endometrial cancer (EEC). MATERIAL AND METHODS: The
      study examined 159 consecutive patients aged 37-86 (62.82 +/- 9.95) with EEC
      stages I-III according to FIGO, treated surgically at the Pirogow Memorial
      Hospital of Lodz between 2000 and 2007. Afterwards they were subsequently treated
      and examined at the Regional Cancer Center Copernicus Memorial Hospital of Lodz.
      Tissue cores 2 mm in size, in duplicate, were taken from the formalin-fixed and
      paraffin-embedded tissue donor blocks from surgery and constructed into the TMA
      recipient blocks. Using TMA method, the relationship between Ki-67 expression,
      DFS and OS was examined. DFS was defined as a period from primary surgery until
      relapse. OS was defined as a period from primary surgery until the end of the
      follow-up (60 months) or until the death of the patient. The study was approved
      by the Ethics Committee of the Medical University of Lodz (RNN/82/11/KE;
      KE/1673/12). RESULTS: The follow-up time varied between 3-60 months (51.42 +/-
      15.87). In 31 patients (19.50%) the relapse of was diagnosed 1-59 months (24.97
      +/- 16.08) after commencement of the treatment. During follow-up 32 patients
      (20.12%) died. DFS and OS were 80.50% and 79.88%, respectively The lack of Ki-67
      expression was found in 37 cases (23.27%) while in 122 patients (76.73%) the
      expression was present (p < 0.001). The expression of Ki-67 in 1-10%, 11-20% and
      > 20% was present in 76 cases, 26 cases and 20 cases, respectively Positive
      correlation between the expression of Ki-67 and staging was present (r = 0.353; p
      < 0.001). In EEC patients with no relapse diagnosed during follow-up the
      expression of Ki-67 was present in 7.63 +/- 7.57% of EEC cells, when compared to
      23.06 +/- 22.93% in EEC patients in relapsed disease (p < 0.001). The
      relationship between increased Ki-67 expression and increased grading was not
      statistically significant (r = 0.149; p = 0.061). The expression of Ki-67 did not
      depend on patient age (r = 0.040; p = 0.617). In univariate analysis negative
      correlation was found between the expression of Ki-67 and DFS (p < 0.001) and OS
      (p = 0.01). In multivariate analysis worse DFS was related to higher staging of
      EEC (p < 0.0 01) and increased expression of Ki-67 (p < 0.001). Worse OS was
      related to higher staging in multivariate analysis (p < 0.001). Ki-67 expression
      was not related to OS in multivariate analysis. Age of patients and grading of
      the EEC were not related to DFS and OS. CONCLUSIONS: The expression of the Ki-67
      can significantly affect therapeutic decisions in selected EEC patients. The high
      Ki-67 expression in EEC patients is related to increased risk of relapse. The TMA
      technique is a good method for the assessment of the Ki-67 in studies conducted
      in EEC patients and makes it easier to carry out immunohistochemistry in large
      populations of patients.

PMID- 24032263
TI  - The impact of thrombocytosis on clinicopathological prognostic factors and
      survival in patients with vulvar cancer.
AB  - PURPOSE: Reactive thrombocytosis in many solid tumors has widely been studied. In
      the present study we aimed to investigate whether thrombocytosis is a common and
      prognostic factor in women with vulvar cancer MATERIAL & METHODS: The
      preoperative platelet counts of 41 women, treated for vulvar cancer in our onco
      gynecology center between March 1994 and January 2007, were retrospectively
      reviewed and correlated to clinical and pathological prognostic factors and 5
      year survival. The chi-square or Fisher exact tests were used to compare
      categorical variables. P value < 0.05 was accepted for statistical significance.
      RESULTS: The mean age was 65.4 +/- 11.3 years (range 39-83y). All patients had
      squamous histology The mean platelet count was 335.42 x 109/L +/- 82.03 (range
      142-1155x109/L). Thrombocytosis was detected in 8 (19.5%) patients. No
      correlation was found between thrombocytosis and grade (p = 0.65), LVSI (p =
      0.82), tumor size (p = 0.73), depth of invasion (p = 0.18), lymph node metastasis
      (0.93), and FIGO stage (p = 0.78). The mean follow up time was 118.0 +/-43.1
      months (range 60-213 months). At the end of the study period 14 patients (34.2%)
      had died, 8 (19.5%) had recurrence, 19 (46.3%) were disease-free. General 5-year
      survival was 68.3% (28/41). The 5-year survival rate for patients with
      thrombocytosis was 75.0% (6/8), which was not significantly different from the 5
      year survival of patients with normal platelet counts (22/33; 66.7%) (p = 0.75).
      CONCLUSION: Our study showed that, overall, thrombocytosis was found in about 20%
      of patients with vulvar cancer and proved to be not linked to the best known
      prognostic factors and survival. Thus, disease stage and inguinofemoral lymph
      node status continue to be the best prognostic factors for this disease.

PMID- 24032264
TI  - [The role of vitamin D deficiency in the etiology of polycystic ovary syndrome
      disorders].
AB  - Vitamin D deficiency connected with insufficient production in the skin and
      limited alimentation delivery disrupts the function of all systems of the body
      and increases the risk of chronic diseases. Many studies have reported
      associations between low serum 25-hydroxyvitamin D [25(OH)D] level and symptoms
      of the polycystic ovary syndrome (PCOS) - insulin resistance, hirsutism, and
      infertility associated with both, ovulatory disorders and abnormal endometrial
      receptivity. The beneficial effects of vitamin D supplementation on insulin
      resistance, ovarian follicles maturation, ovulation and menstrual regularity were
      confirmed. Due to limited evidence, the additional randomized trials are required
      to establish the correct dose of vitamin D and confirm the effectiveness of
      vitamin D treatment in PCOS disorders. However; it seems evident that correct
      supplementation of vitamin D is beneficial in the management of women with PCOS
      and low 25(OH)D serum levels, and that it could be helpful in improving the
      effects of PCOS treatment.

PMID- 24032265
TI  - Multiplex ligation-dependent probe amplification (MLPA)--new possibilities of
      prenatal diagnosis.
AB  - Multiplex Ligation-dependent Probe Amplification (MLPA) is a relatively new
      method of molecular diagnosis. It enables a relative quantitative assessment of
      up to 50 different PCR amplicons in one reaction by the use of a very small
      amount of examined DNA. Nowadays MLPA is becoming a very helpful tool in prenatal
      diagnosis and is widely used for the detection of aneuploidies, familial single
      gene disorders, common microdeletion syndromes, sub-telomeric alterations and
      identification of marker chromosomes in fetuses. This review demonstrates
      possible applications of MLPA in prenatal diagnosis.

PMID- 24032266
TI  - [Modified posterior exenteration (radical oophorectomy type II) as a part of an
      extensive surgery of ovarian cancer--case report].
AB  - Epithelial ovarian cancer remains to be the most deadly gynecologic cancer among
      the female population. Carcinogenesis and abdomen extension are the reasons why
      ovarian cancer is still examined in advances stages. Ovarian cancer frequent
      metastasizes to the uterus, rectosigmoid colon, and other pelvic structures by
      intraperitoneal seeding of tumor deposits, as well as direct extension. Multiple
      modalities of therapy are utilized in the management of the disease. Numerous
      medical trials and research programs have demonstrated the most important role of
      surgery in the treatment of this disease. A vast majority of authors are of the
      opinion that the surgical interventions have a major influence on the overall
      survival (OS) and progression free survival (PFS) in ovarian cancer cases. The
      paper presents a case of a 35-year-old woman diagnosed with advanced ovarian
      cancer who underwent modified posterior exenteration as a part of extensive
      cytoreductive surgery

PMID- 24032267
TI  - [Diagnostic and therapeutic dilemmas in pregnant woman with pulmonary embolism].
AB  - Hypercoagulable state during pregnancy and puerperium is associated with an
      increased risk of venous thromboembolic disease. Pulmonary embolism (PE) is the
      leading cause of maternal death in the developed world. Clinical assessment of PE
      may be difficult due to nonspecific signs and symptoms, especially in pregnant
      women. Diagnostic procedures using ionizing radiation may be harmful for the
      fetus while aggressive anticoagulation may expose the mother to bleeding
      complications The aim of this paper was to present a case of a 27-year-old
      pregnant woman with high-risk PE.

PMID- 24032268
TI  - [Acute heart failure due to myocarditis in the first trimester of pregnancy].
AB  - The incidence of cardiovascular diseases in pregnancy is estimated at about 1%.
      Pregnant women suffer from rheumatic diseases of the heart valves, hypertension,
      congenital heart deffects, inflammatory and ischemic disorders or pathologies of
      the electrical conduction system of the heart. Myocarditis during pregnancy
      occurs very seldom. Few cases of severe myocarditis during gestation have been
      reported in the literature. This report presents a case of a 27-year-old Asian
      patient, at 8 weeks of gestation, diagnosed with an acute myocarditis. The woman
      was admitted to the hospital, presenting with early and nonspecific symptoms,
      (fever up of 38.5 degrees Celsiuss, abdominal pain and nausea). After temporary
      improvement, the patient's condition deteriorated. On the fourth day of the
      hospitalization, myocarditis led to heart failure and the patient had to be
      transffered to the Intensive Care Unit. Wide-spectrum antibiotics,
      glucocorticoids, diuretics, bisoprolol, as well as fluid and electrolyte
      supplementation, were administered. After 22 days of treatment the patient was
      discharged home in good condition. Afterwards she attended follow-up visits at
      the Gynecology-Obstetric Outpatient Clinic. She delivered a healthy son (2340
      grams, 51 centimetres, Apgar 10) at 37 weeks of gestation. At present, she
      remains under the care of the Cardiac Clinic and requires small doses of
      bisoprolol because of periodic supraventricular arrhythmias.

PMID- 24032269
TI  - Quercetin inhibits proliferation and increases sensitivity of ovarian cancer
      cells to cisplatin and paclitaxel.
AB  - INTRODUCTION: Due to frequent diagnosis of ovarian cancer at an advanced clinical
      stage, in most cases surgical debulking is followed by chemotherapy. The
      principal cause of therapeutic failure involves incomplete surgery and resistance
      of neoplastic cells to chemotherapy. A search continues for substances which
      would overcome resistance to treatment and, as a result, would increase efficacy
      of the applied treatment. Quercetin represents one of more interesting compounds,
      which at present in subjected to several tests. MATERIAL AND METHODS: Studies
      were performed on in vitro sensitivity of human ovarian cancer cell lines, SKOV
      3, EFO27, OVCAR-3 and A278OP to low doses of quercetin and on the effect exerted
      by quercetin on sensitivity of the cell lines to cisplatin and pactitaxel.
      RESULTS: The experiments proved that the studied cells of ovarian cancer manifest
      a similar sensitivity to quercetin. Following incubation of the cells with two
      distinct concentrations of quercetin and the studied cytostatic agents all the
      cells lines were found to significantly increase their sensitivity to pactitaxel
      in cases of two cell lines, OVCAR-2 and A278OP, they also significantly increased
      their sensitivity to cisplatin. DISCUSSION: Our results demonstrated suitability
      of low quercetin doses (achievable using oral administration) as a substance
      which increases sensitivity of ovarian cancer cells to cisplatin and paclitaxel.
      The value of quercetin include its wide accessibility efficacy and a broad range
      of activity but also its low toxicity as compared to other examined compounds.
      CONCLUSIONS: Used in low doses, quercetin increases chemosensitivity of ovarian
      cancer cells examined compounds.

PMID- 24032270
TI  - [Evaluation of safety and effectiveness of pelvic organ prolapse treatment with
      the use of polypropylene mesh depending on mesh and application technique].
AB  - OBJECTIVES: Evaluation of safety and effectiveness of POP (pelvic organ prolapse)
      treatment with the use of polypropylene mesh depending on type of mesh and
      application technique. MATERIALS AND METHODS: We carried out a retrospective
      study and compared the frequency of perioperative complications and treatment
      results three months after the surgical procedure in two groups of patients,
      divided according to POP type. The first group comprise of patients with anterior
      compartment disorders who had Prolift Anterior (n = 100) or Pelvimesh Anterior (n
      = 98) placed. The second group included patients with posterior and central
      compartment who had Prolifit Posterior (n = 72) and Pelvimesh Posterior (n = 89)
      fitted. Early peri- and postoperative complications criteria were: profuse
      intraoperative bleeding (hemoglobin decrease of 3g%), intraoperative damage of
      urinary bladder and bowel, presence of hematoma in paravesical and perirectal
      space, urine retention after miction on the second day after the operation (> 100
      ml), uroschesis after catheter removal, early operative failure (during 3 months
      after the operation), mesh erosion. RESULTS: No statistically significant
      differences in peri- and postoperative complications were reported between the
      studied groups (Pelvimesh vs. Prolift). No damage of urinary bladder or bowel was
      found in any of the studied groups. Other complications in Prolift Ant. Vs.
      Pelvimesh Ant groups were: postoperative anemia (4.00% vs. 4.09%); presence of
      hematoma (1.00% vs. 1.03%); postoperative urine retention (7.00% vs. 5.11%);
      uroschesis (1.00% vs. 1.03%); mesh erosion (2.00% vs. 1.03%); early operative
      failure (1.00% vs. 3.07%). Early postoperative results did not statistically
      differ between the Pelvimesh and the Prolift group. Results in the Prolift Post.
      vs. Pelvimesh Post. Groups were: postoperative anemia (2.78% vs. 5.62%); mesh
      erosion (1.38% vs. 0%), early operative failure (1.38% vs. 5.62%). Damage to
      bowel and hematoma was not observed in these groups. CONCLUSIONS: Our research
      failed to observe an advantage of any of the ready POP treatment kits. Despite
      application of different systems for mesh placement and pulling the arms through
      ligaments (either obturator foramen or sacrospinous ligament), no statistically
      significant differences were demonstrated with regard to the occurrence of early
      peri- and postoperative complications or efficiency in POP treatment in Prolift
      Anterior vs. Pelvimesh Anterior and Prolift Posterior vs. Prolift Pelvimesh
      groups.

PMID- 24032271
TI  - Comparison of two doses of recombinant hcg for oocyte maturation in obese women
      (BMI > or = 30) undergoing assisted reproductive techniques.
AB  - OBJECTIVE: To compare the efficacy of two doses (250 microg vs. 500 microg) of r
      hCG for oocyte maturation in obese women with a body mass index (BMI) > or = 30
      and undergoing assisted reproduction techniques. MATERIALS AND METHODS: A
      Prospective, randomized, clinical study of seventy two patients undergoing IVF/
      intracytoplasmic sperm injection cycles with BMI > or = 30 kg/m2. Patients with
      high BMI were randomized to receive either 250 microg or 500 microg rhCG. Blood
      and follicular fluid (FF) samples were collected on the day of oocyte pick-up
      (OPU). The outcome measures were serum and FF hCG levels on the day of OPU,
      number of oocytes retrieved per patient, number of mature oocytes retrieved,
      clinical pregnancy rates (PR). RESULTS: Serum hCG levels were significantly lower
      in patients receiving 250 microg of r-hCG than in patients receiving 500 microg
      of r-hCG. However FF hCG levels, implantation rates, abortion rates, clinical PRs
      were not significantly different. CONCLUSIONS: 250 microg of r-hCG is sufficient
      and safe to trigger ovulation in women with BMI > or = 30.

PMID- 24032272
TI  - [Analysis of the demographic profile of patients treated for infertility using
      assisted reproductive techniques in 2005-2010].
AB  - OBJECTIVES: Analysis of the demographic profile of patients, causes for
      infertility and effectiveness of infertility treatment methods in the years 2005
      2010. MATERIAL AND METHODS: Retrospective research was conducted to analyze data
      of 1705 randomly selected couples who underwent in vitro fertilization procedure
      at the Department of Reproduction and Gynecological Endocrinology Medical
      University of Bialystok, between 2005 and 2010. The analyzed data included mainly
      causes for infertility age of the female and male subjects, place of residence
      and final treatment results. RESULTS: The percentage of pregnancy rate increased
      significantly to approximately 40% in 2007. The contribution of male and female
      infertility factors remained at a similar level, but the idiopathic factor
      continued to steadily increase (to 20% in the last years of the study). We
      observed a greater prevalence of the male factor among couples living in cities
      compared to inhabitants of rural areas (42.3% vs. 34.3%, p = 0.004), whereas the
      tubal factor dominated among couples living in the countryside when compared to
      city dwellers (29.7% vs. 21.6%, p = 0.001). The average age of women entering
      treatment was significantly higher in cities than the countryside (p < 0.001),
      thus, consequently treatment efficacy was also lower (33.9% vs. 38.9%, p = 0.04).
      Comparison of treatment efficacy and cause of infertility revealed statistically
      significant differences only with regard to the idiopathic factor (p = 0.03). In
      the group of patients with idiopathic infertility the treatment efficacy was
      higher than in the rest of patients (40.2% vs. 33.8%). Apart from the idiopathic
      infertility only the presence of the male factor was associated with a higher
      (but statistically insignificant) pregnancy rate (36.2% vs. 33.9%). For the other
      factors, their presence was associated with a lower percentage of pregnancy and
      the greatest differences (but still statistically insignificant) were observed
      for the polycystic ovary syndrome (31.5% vs. 35.1%) and for other ovulation
      disorders (31.3% vs. 35%). CONCLUSIONS: Advances in assisted reproductive
      techniques led to an increase in the efficacy of infertility treatment.
      Environmental factors, availability of treatment and level of awareness about
      womens health proved to have the strongest effect on the distribution of
      infertility causes between urban and rural areas. Significant efforts should be
      made, especially in cities, to decrease the average age of women's reproductive
      decisions and also to shorten the time to the first contact with the specialist
      after unsuccessful attempts at conception. It is also crucial to initiate the
      reimbursement of infertility treatment using ART (Assisted Reproductive
      Technology).

PMID- 24032273
TI  - [Laboratory diagnosis of genital herpes--direct immunofluorescence method].
AB  - OBJECTIVES: Aim of the study was to determine clinical usefulness of direct
      immunofluorescence method in the laboratory diagnosis of genital herpes in women.
      MATERIAL AND METHODS: Overall 187 anogenital swabs were collected from 120 women.
      Using a dacron-tipped applicator 83 swabs were collected from women suspected of
      genital herpes and 104 from patients with no signs of genital infection. All
      samples were tested using cell culture (Vero cell line) and then direct
      immunofluorescence method (DIF) for the identification of antigens of herpes
      simplex viruses: HSV-1 and HSV-2. RESULTS: Characteristic cytopathic effect
      (CPE), indicative of alphaherpesvirus infection, was observed in 43.4% of
      cultures with clinical specimens collected from women with suspected genital
      herpes and in 29.8% of cultures of clinical specimens taken from patients with no
      clinical symptoms of genital herpes. Herpes simplex viruses were determined in 73
      samples by direct immunofluorescence method after amplification of the virus in
      cell culture. The DIF test confirmed the diagnosis based on the microscopic CPE
      observation in 85%. In 15% of samples (taken from pregnant women without clinical
      signs of infection) we reported positive immunofluorescence in the absence of
      CPE. The frequency of antigen detection was statistically significantly higher in
      samples that were positive by culture study (chi-square test with Yates's
      correction, p < 0.01). This method proved to be highly sensitive (97%) in women
      with clinically suspected infection. High negative predictive value (99%) proves
      the clinical utility of the DIF in these group of patients. In asymptomatic
      infections, viral antigens were detected most frequently in the swabs from the
      cervical canal, and in cases of suspected genital herpes in swabs taken from the
      vestibule of the vagina and the vulva. However, there was no statistically
      significant difference in the frequency of detection of Herpes Simplex Virus
      antigens in specimens from different parts of the genital tract in both groups of
      women (chi-square test, p > 0.05). In our study HHV-1 was the main causative
      agent of genital herpes. CONCLUSIONS: The growing worldwide prevalence of genital
      herpes, challenges with the clinical diagnosis, and availability of effective
      antiviral therapy are the main reasons for a growing interest in rapid, proper
      laboratory diagnosis of infected patients. Optimal testing diagnostic algorithm
      depends on patient population, clinical circumstances and availability. Our
      results indicated that combination of laboratory tests may help to establish the
      diagnosis if genital herpes is suspected but there are no typical signs.

PMID- 24032274
TI  - Placental growth hormone (PGH), pituitary growth hormone (GH1), insulin-like
      growth factor (IGF-I) and ghrelin in pregnant women's blood serum.
AB  - OBJECTIVES: The aim of this work is to evaluate levels of placental growth
      hormone (PGH), pituitary growth hormone (GH1), insulin-like growth factor (IGF-I)
      and ghrelin in pregnant women's blood serum before, during and after delivery.
      Furthermore, the aim is to search for links and interdependence of GH1, PGH and
      IGF-I concentrations. MATERIAL AND METHODS: Seventy nine blood samples were taken
      one to two hours before, during and half an hour after expulsion of placenta. All
      proteins studied were determined by ELISA method, using ELISA Kit. RESULTS: The
      highest PGH concentration and IGF-I concentration in pregnant women's blood serum
      was observed before delivery while GH1 concentration was lowest. During and after
      delivery PGH and IGF-I concentration decreased proportionately and pituitary
      growth hormone concentration increased accordingly. About half an hour after
      delivery of the placenta, GH1 concentration was highest. CONCLUSIONS: In pregnant
      women's blood there is a metabolic interdependence between PGH and IGF-I. Their
      concentration increases proportionately during pregnancy and decreases after
      delivery. It appears that labor and delivery releases GH1 blockade, which level
      rises three-fold during delivery. After parturition its role and concentration
      returns to levels before pregnancy.

PMID- 24032275
TI  - [Frontomaxillary facial angle measurement at 11+0 to 13+6 weeks' gestation.
      Application in every day prenatal diagnosis of trisomy 21].
AB  - OBJECTIVE: The aim of the study was to evaluate the effectiveness of prenatal
      screening for trisomy 21 with the use of the FMF angle measurement, depending on
      the disease risk group. MATERIAL AND METHODS: The study included 2,026 single
      pregnancy fetuses, examined in years 2009-2011. The crown-rump length, nuchal
      translucency and frontomaxillary facial angle were measured for each of the
      fetuses according to the Fetal Medicine Foundation guidelines. All ultrasound
      exams were performed using trans-abdominal probes paired with Voluson 730 Expert
      and Expert E8 systems. All physicians conducting the exams were FMF-certified
      professionals. Maternal age at the time of the study was also reported. In 1621
      pregnant women serum concentration of PAPP-A was determined using Delfia Express
      system (Perkin Elmer). Astraia software was used to assess fetal risk of trisomy
      21. The final analysis included 791 fetuses which were followed up for the
      occurrence of trisomy 21. Data were analyzed using PQStat package ver 1.4.2.324.
      Highly significant likelihood was set at p < 0.01 and significant likelihood at p
      < 0.05. RESULTS: Average maternal age was 31.42 years (median: 32 in a range from
      27 to 45). Average FMF angle was 76.24 degrees (median: 75 degrees in a range
      from 69 to 04). Average CRL measurements was 63.70 mm (median: 64.10 mm in a
      range from 45 to 84). Average NT measurement was 1.91 mm (median: 1.6 mm in a
      range from 0.50 to 9.3). There was no significant (p > 0.05) correlation between
      maternal age and FMF. Highly significant (p < 0.01) negative correlation between
      the CRL and the FMF angle was found. There were 41 fetuses with trisomy 21 (Down
      syndrome) in the study group. In the normal karyotype group, the FMF angle was
      highly significantly lower (p < 0.0001) than in the trisomy 21 group. 95th
      percentile of the each of four separated CRL ranges was calculated. Detection
      rate and false positive rate for each of four different risk levels were
      estimated. They were used as cutoff points for two models of first trimester
      screening compared: Model 1, including maternal age, NT measurement and PAPP-A
      test, and Model 2, including maternal age, NT measurement, PAPP-A test and
      Frontomaxillary facial angle measurement. CONCLUSIONS: 1. Detection rate (DR) of
      the Down syndrome increases after the introduction of FMF angle measurement as an
      additional component of screening including maternal age, NT measurement and PAPP
      A test. 2. Introduction of the FMF angle as an independent marker for fetal
      trisomy 21 risk requires further research on large populations.

PMID- 24032276
TI  - [Therapeutic and prognostic value of lymphadenectomy in gynecological oncology].
AB  - Lymphadenectomy is an integral part of gynecological cancer surgery however there
      is still lack of standardization in the terminology used. In the current
      literature several types of surgical procedures for pelvic lymph nodes dissection
      are recognized. Complete pelvic lymphadenectomy is defined as the removal of all
      fatty lymphatic tissue from the predicted areas of high incidence of lymph nodes
      with possible metastatic involvement. Para-aortic lymphadenectomy is defined as
      the removal of all lymphatic tissue from the aortic region. The latter is divided
      into two levels: the lower--up to the inferior mesenteric artery and the upper-
      up to the left renal vein. Another classification divided pelvic and aortic
      lymphadenectomy into three classes. Class I is defined as the removal of the
      chosen lymph nodes, class II as the removal of lymph nodes located ventrally and
      laterally to the large retroperitoneal pelvic vessels, obturator nerves and
      laterally to the aorta and the inferior vena cava, whereas class III as the
      complete removal of lymphatic tissue surrounding the iliac vessels, obturator
      pits, dorsally to the obturator nerve and the presacral lymph tissue around the
      aorta and the inferior vena cava. In each gynecological cancer depending on the
      severity of the disease different procedures are applied concerning
      lymphadenectomy. In patients with advanced ovarian cancer systematic
      lymphadenectomy prolongs the survival rate. Omission of systematic
      lymphadenectomy can be considered only for patients with mucinous carcinoma G1
      level. In the case of vulvar cancer removal of pelvic, iliac and obturator lymph
      nodes is inappropriate as it has not been proven to result in an increased
      survival rate. Inguinal lymphadenectomy in this cancer depends on the stage and
      location of the primary tumor--at an early stage vulvar cancer located laterally
      a superficial, unilateral inguinal lymphadenectomy can be performed, if the
      primary lesion is located centrally an inguinal lymphadenectomy should be
      performed on both sides. Deep inguinal lymphadenectomy should be performed only
      in cases where: primary tumor is located centrally in case of cancer in the early
      stages, in advanced stage and in patients with metastases in the superficial
      nodes. Sentinel lymph node biopsy is an alternative method that can be offered to
      patients with early-stage vulvar cancer located laterally. Lymphadenectomy in
      endometrial cancer is beneficial in stages I G3, II and III. In stages I G1 and
      G2 an increase in the survival time has not been shown. The cervical cancer stage
      IB-IIA removal of para-aortic lymph nodes (to the mesenteric artery) is indicated
      in patients with large tumors and suspected or known disease in the pelvic nodes.
      In patients in whom diagnostic imaging studies have not shown metastasis in para
      aortic and pelvic lymph nodes or distant metastasis, para-aortic lymphadenectomy
      can be omitted. Further randomized studies are needed to elucidate the necessity
      and extent of lymphadenectomy in given gynecological cancers.

PMID- 24032277
TI  - [Legal aspects of selling medical products by gynecologists].
AB  - Sales and distribution of medical products and drugs in Poland remains under
      strict regulations, especially legal regulation contained in the Medical and
      Dental Practitioners Act, that banned sales of medical products by doctors. It
      needs to be emphasized that currently doctors are allowed to sell drugs and
      medical products only in rigorously specified situations. Knowledge of current
      legal regulations concerning sales of medical products by gynecologists allows to
      conform with the law and to distribute drugs and medical products under special
      and predefined conditions.

PMID- 24032278
TI  - [Metafolin--alternative for folate deficiency supplementation in pregnant women].
AB  - Proper folate supplementation is required in order to ensure proper folate
      concentration in the organism, and consequently to prevent the development of
      numerous complications in general population and pregnant women. Metafolin
      (stable calcium salt of L-5-methyltetrahydrofolate acid, L-5-MTHF) is the most
      active form of reduced folate circulating in plasma, which directly enters the
      metabolic process of folate. After administration metafolin shows optimum
      absorption, comparable or higher bioavailability as well as physiological
      activity when compared to folic acid. Metafolin supplementation is effective in
      decreasing plasma homocysteine, as well as increasing folate in plasma and
      erythrocytes, in pregnant and breastfeeding women or those who wish to conceive.
      In addition, metafolin administration omits the multistage process of reduction
      before entering the folate cell cycle, as well as a possible deficiency of
      activity of enzymes participating in the reduction of folate process in the
      intestine epithelium (DHFR and MTHFR enzymes). So far no potential adverse and
      toxic effects of metafolin management have been reported. The published findings
      require confirmation in larger groups of patients and an additional analysis of
      the presence of particular genotypes of 677C > T polymorphism of the MTHFR gene.
      Analysis of the recent literature reposts suggests that metafolin could be an
      effective and safe alternative to folic acid supplementation and could
      effectively prevent complications in pregnancy and series birth defects in
      fetuses and newborns.

PMID- 24032279
TI  - Recurrent spontaneous ovarian hyperstimulation in a virgin girl.
AB  - Ovarian hyperstimulation syndrome (OHSS) develops due to the release of
      vasoactive mediators induced by excessively luteinized and enlarged ovaries. Most
      OHSS cases are iatrogenic subsequent to ovulation induction. We report the first
      case of recurrent OHSS developed during normal menstral cycle in a virgin girl,
      diagnosed with ultrasonography and magnetic resonance imaging.

PMID- 24032280
TI  - [Bilateral metastases of renal cell carcinoma to the ovaries--a case report].
AB  - Renal cell carcinoma accounts for 75% of renal neoplasms. Clear cell carcinoma is
      diagnosed in about 80% of the cases. Renal cell carcinoma most frequently
      metastasizes to the lungs (50-60%), lymph nodes (36%), bones (30-40%), liver (30
      40%), and brain (5%). In other organs the metastasis changes are observed very
      rarely. Ovarian metastases are found in 0.5% of renal cancers. So far, only 23
      cases of renal cell carcinoma metastases to the ovary have been reported in the
      literature. In 18 cases they were metastases of renal cell carcinoma of the clear
      cell type. The authors present a case of a 50-year-old woman with double-sided
      metastatic changes to the ovary from renal cell carcinoma. The patient was
      admitted to the Gynecological ward with preliminary diagnosis of ovarian tumors.
      Gynecological examination revealed double-sided ovarian tumors, 6-7cm in
      diameter. Computed tomography also showed a 155 x 80 mm hetrogenous, multiform
      tumor localized above the uterus. In addition, CT showed a 75 x 55 mm tumor in
      the lower pole, and a smaller one, 15 mm in diameter in the upper pole of the
      right kidney. Laboratory tests were normal. The antigen Ca 125 was 25 j/ml.
      Mammography cytology gastroscopy colonoscopy were normal. The consulting
      urologist proposed a two-stage treatment. In the first stage, the removal of the
      double-sided ovarian tumors was proposed, while in the second stage the right
      nephrectomy was suggested. Double-sided ovarian tumors were found and removed (in
      the wall of the cyst- yellow, solid masses) during the first operation.
      Intraoperative histological examination showed changes with unknown grade of
      malignancy in both ovaries (number of studies QN 291). The patient underwent
      total hysterectomy. On day 5 postoperatively the woman was discharged from the
      hospital in good condition with the recommendation to pick up the histological
      test result in two weeks time. The final histological examination showed
      metastatic changes of renal cell carcinoma of the clear cell type (number of
      studies QN569-582, QN 585-608). The diagnosis of bilateral renal cell carcinoma
      metastases to the ovaries was confirmed by immunohistochemical studies using
      antibodies CD 10 and Vimentin (number of studies CT 1558-1559). The patient was
      directed to the Urological Ward. The surgery confirmed the presence of the tumor
      in the lower pole (about 8 cm in size), and a smaller one (about 1 cm in size) in
      the upper pole of the right kidney. The right nephrectomy was performed.
      Histological examination confirmed the primary clear cell renal cell carcinoma.
      The patient was directed to the next oncological treatment.

PMID- 24032281
TI  - Pregnancy delivery and puerperium in a patient with lysinuric protein intolerance
      -a case report.
AB  - The paper presents the course of pregnancy delivery and early postpartum period
      in a 23-year-old woman with lysinuric protein intolerance (LPI). The pregnancy
      was uneventful and resulted in a caesarean birth to a healthy baby at 37 weeks
      gestation. Nevertheless, the course of pregnancy in women with LPI is associated
      with a significantly increased risk of serious complications, including acute
      hyperammonemia, preeclampsia and postpartum bleeding, as well as fetus
      intrauterine growth retardation. In many cases, intensive metabolic monitoring
      and a proper diet with protein limitation and appropriate amino acids
      supplementation may significantly reduce the risk for both the mother and the
      newborn.

PMID- 24032282
TI  - GAPO syndrome associated with pyoderma vegetans: an unreported co-existence.
AB  - GAPO syndrome is a rare autosomal recessive disease and an acronym composed of
      growth retardation, alopecia, pseudoanodontia, optic atrophy. Approximately 38
      cases have been reported in literature until now. Pyoderma vegetans is a chronic
      inflammatory disease characterized with vesicopustular, exudative and vegetative
      lesions usually localized on face, scalp, axilla and genitalia. Pyoderma vegetans
      is attributed to a bacterial infection frequently occurring in individuals with
      an underlying immunosuppressive condition. A 30-year-old female patient was
      admitted to our clinic with complaint of a hemorrhagic, crusted, exudative
      vegetative two plaques on the scalp. On her physical examination, she had a
      prematurely aged face, predominant lower lips, total tooth loss, frontal bossing,
      enlarged anterior fontanelle, marked scalp veins, micrognatia, depressed nasal
      bridge, short stature, growth retardation. She was diagnosed as GAPO syndrome as
      the result of her physical examination. Result of the biopsy taken from scalp was
      evaluated as pyoderma vegetans. And the diagnosis of pyoderma vegetans was
      established based on the correlate of both clinical and histopathologic findings.
      Pyoderma vegetans coexisting with GAPO syndrome has not been reported previously.
      Thus we wished to report it.

PMID- 24032283
TI  - A novel mutation of laminin beta-2 gene in Pierson syndrome manifested with
      nephrotic syndrome in the early neonatal period.
AB  - Pierson syndrome is a rare autosomal recessive disorder which is mainly
      characterized by congenital nephrotic syndrome (CNS), diffuse mesangial sclerosis
      (DMS) and distinct ocular abnormalities, including microcoria. Most affected
      children exhibit early onset of chronic renal failure, neurodevelopmental
      deficits, and blindness. It is caused by a homozygous or compound heterozygous
      mutation in the gene encoding laminin beta2 (LAMB2) on chromosome 3p21. In this
      article, we report on a patient with CNS, bilateral megalocornea and microcoria.
      The patient had developed renal failure at very early postnatal period and died
      of septic shock. A novel homozygous donor splice mutation (IVS4 + 2T > C) in
      LAMB2 gene was identified in the patient.

PMID- 24032284
TI  - Genomic damage in patients with type-2 diabetes mellitus.
AB  - DNA damage seems to play a role in the pathogenesis of type-2 diabetes mellitus
      (DM2) and its complications. Several in vitro assays have been used to measure
      the DNA damage. In the present study, we aimed to investigate the frequency of
      sister chromatid exchange (SCE) and micronuclei (MN) in DM2 patients compared
      with healthy controls. SCE and MN tests were carried out with the blood-cell
      cultures from 50 DM2 patients and 30 healthy, age- and sex-matched control
      subjects. The mean age of the DM2 patients was 58.12 +/- 13.39 years, with a mean
      duration of the diabetes of 5.40 +/- 4.32 years. The mean level of HbAlc of the
      DM2 patients was 8.93 +/- 2.56. Patients with DM2 showed a higher frequency of
      SCE compared with controls (7.11 +/- 1.14 and 4.96 +/- 0.92, p < 0.001).
      Furthermore, the SCE frequency was positively correlated with the plasma HbA1c
      level (p < 0.05), but there was no significant correlation between the duration
      of diabetes and SCE. On the other hand, our result showed a MN frequency
      significant increase in DM2 patients (3.45 +/- 1.01 per 1000 cells) relative to
      that of the control group (1.79 +/- 0.67 per 1000 cells) (p < 0.001), but there
      was no significant correlation between the duration of diabetes, HbA1c and MN. In
      conclusion, these results suggest that DM2 is a condition with genomic
      instability characterized by an increased level of SCE and MN. Hyperglycemia
      induced oxidative stress may be the underlying factor of the increased SCE and MN
      frequency.

PMID- 24032285
TI  - Anal atresia, abnormal genitalia, and absent thumb: congenital malformations
      associated with mosaic ring chromosome 13.
AB  - Because of the deletion of a segment of the chromosome during the formation of a
      ring, several clinical findings may be associated with ring chromosomes. Ring
      chromosome 13 is one of such disorders in which the genotype-phenotype
      correlation is stronger by virtue of the accumulating literature. It can be
      associated with multiple congenital abnormalities and severe mental retardation.
      We report a case with mosaic ring chromosome 13 whose prenatal ultrasound
      revealed bilateral ventriculomegaly. Anal atresia, unidentifiable external
      genitalia, and an absent thumb were observed in the postmortem examination.

PMID- 24032286
TI  - Crisponi syndrome: a new mutation in CRLF1 gene associated with moderate outcome.
AB  - SUMMARY: Crisponi syndrome (CS) is a rare, autosomal recessive disorder,
      characterized by hyperthermia, extensive muscular contractions in the face after
      even minimal stimuli or crying, hypertonia, opisthotonus, camptodactyly, and
      typical facial features. Recently, it has been demonstrated that CRLF1 (cytokine
      receptor-like factor 1) gene mutation is associated with CS. Here we report a
      case of CS with a new mutation in the CRLF1 gene associated with moderate
      clinical phenotype.

PMID- 24032287
TI  - Subtelomeric rearrangements in patients with idiopathic intellectual disabilitiy/
      multiple congenital anomalies and recurrent miscarriages: seven years'
      experience.
AB  - Cryptic subtelomeric anomalies are a significant cause of idiopathic intellectual
      disability and/or multiple congenital anomalies (ID/MCA) and multiple
      miscarriages (MM). Effective preselection of patients is essential as the cost of
      subtelomeric testing is high and it is labor-intensive. Therefore, the aim of
      this study is to evaluate the frequency of subtelomeric anomalies by using
      commercial FISH probes in 151 patients of ID/MCA and 32 couples with MM who were
      referred to a genetic center during 7-year period and to determine whether
      performing subtelomeric testing is feasible for these groups of patients. We
      assessed the clinical information of all referrals including family history,
      physical examination, facial dysmorphism, congenital malformations and scored the
      ID/MCA patients according to the criteria suggested previously. The etiology was
      not elucidated and all patients had normal karyotypes. Subtelomeric deletions
      were found in 10 patients in ID/MCA group (6.62%). These were deletions of 14qter
      (2 patients), 18qter (2 patients), 18pter (2 patients), 15qter, 7pter, 8pter and
      4qter. The clinical information of all patients having deletions has been
      summarized and confined with the current literature. No anomaly was detected in
      the MM group. In conclusion, the prevalence of subtelomeric anomalies in ID/MCA
      group in this study is consistent with the literature and subtelomeric FISH
      analysis is feasible in determining their etiology when a checklist is used.
      Besides, assessment of the genetic basis of ID/MCA had lead the prevention of the
      recurrence of such conditions in selected families as well as elucidating novel
      genetic causes of ID.

PMID- 24032288
TI  - Partial trisomy 2p24-->pter and monosomy 18q22.1- qter resulting from parental
      translocation.
AB  - This is a report of a 6 month-old boy with a partial trisomy 2p24-->pter and
      monosomy 18q22-->qter. This is the first case presenting this unbalanced
      translocation with phenotypic features. The patient had growth and developmental
      retardation, facial dysmorphism, cleft palate, congenital cardiopathy,
      hypospadias, evantration of diaphragm and deafness. Cranial MRI showed mild
      ventricular dilatation. Cytogenetic analysis of the patient and his parents
      revealed a karyotype 46,XY, der(18), t(2;18)(p24;q22)mat in the patient.
      Subtelomeric FISH analysis confirmed the cytogenetic findings. Phenotypic
      features were consistent with either partial trisomy 2p or deletion 18q.

PMID- 24032289
TI  - Neuhauser syndrome: a rare association of megalocornea and mental retardation.
      Review of the literature and further phenotype delineation.
AB  - Megalocornea can be observed as an isolated abnormality that is inherited by an X
      linked mechanism, or it can be associated with other entities. Megalocornea
      mental retardation syndrome, also known as Neuhauser syndrome, is a rare
      autosomal recessive congenital disorder that presents with megalocornea, mental
      retardation, hypotonia, and facial dysmorphism, among other signs. With the
      report of this new case, and after an extensive review of the literature, we
      attempt to delineate the Neuhauser syndrome phenotype.

PMID- 24032290
TI  - Clinical, cytogenetic and molecular characterization of two cases of mosaic ring
      chromosome 13.
AB  - The occurrence of mosaic ring chromosome 13 is rare. The mechanism of ring
      chromosome formation is usually associated with loss of genetic material. We
      report 2 cases of mosaic ring chromosome 13, resulting in deletion of 13qter. The
      first patient, a 15 year-old boy, presented a delayed psychomotor development,
      mental retardation, dysmorphic features and bleeding disorders associated with a
      de novo terminal 13q34 deletion. The second case was a foetus of 31 weeks with
      prenatal diagnosis of severe malformation such as holoprosencephaly, congenital
      cardiac defects, gastro-intestinal abnormalities with intrauterine growth
      retardation, the molecular analysis showed a de novo deletion encompassing the
      region 13q31.3-q34.

PMID- 24032291
TI  - Papillorenal syndrome with de novo reciprocal translocation t(2;15) (q31; q26).
AB  - Renal hypoplasia is a congenital anomaly, the etiology of which is not yet fully
      known. Genetic studies have shown that certain genes, in utero environmental
      factors and molecular mechanisms have a role in the identification ofnephron
      formation and kidney size. The coexistence of bilateral renal hypoplasia and
      optic disc coloboma is observed in papillorenal syndrome, which caused by the
      mutation of the PAX2 gene. In the case presented in this article, bilateral renal
      hypoplasia and optic disc coloboma have been detected to coexist. The analysis of
      the PAX2 gene, which was carried out with an eye to the papillorenal syndrome,
      did not reveal any mutations. However, de novo t(2;15) (q31; q26) (reciprocal
      translocation) was detected in chromosome analysis. As far as we know, there are
      not any publications focusing on the clinical importance of this type of
      translocation. In cases with renal hypoplasia and optic disc coloboma, the
      possibility of a de novo translocation between chromosomes 2 and 15 should be
      considered.

PMID- 24032292
TI  - Partial proximal trisomy 14: identification and molecular characterization in a
      girl with global developmental delay.
AB  - Chromosomal rearrangements associated with a disease play a significant role in
      the phenotypic manifestation. Here we report a 9-month-old girl with de novo
      partial proximal trisomy 14 with seizures and global developmental delay.
      Cytogenetic investigations revealed a karyotype of 47,XX+marker. The marker was
      approximately the size of G-group chromosomes and almost mistaken as chromosome
      22 due to its banding pattern but the trisomy 22 was ruled out considering its
      lethality. To find out the origin of the marker chromosome, Spectral karyotyping
      (SKY) was performed which showed the marker to be of chromosome 14 origin.
      Further Molecular cytogenetic analysis with whole chromosome 14 confirmed the
      marker as a derivative 14. Fluorescence in situ hybridization (FISH) with
      centromeric probe 14 also showed 3 signals. Further fine mapping with three
      Bacterial Artificial Chromosome clones helped us to tentatively find the extent
      of the break point regions. The use of SKY and FISH permitted the
      characterization of this cytogenetic abnormality. The clinical data of the
      present case are compared with other published cases in the literature. This
      helps in better genetic counseling and also in the genotype/phenotype
      correlation. The impact of the extra chromosomal part in relation with the
      phenotype of the patient is also discussed.

PMID- 24032293
TI  - De novo terminal 4q deletion syndrome with new ocular findings in Turkish twins:
      case report.
AB  - The 4q deletion syndrome is a rare chromosome deletion syndrome with a wide range
      of clinical phenotypes. Herein we report cases of twins (karyotype 46, XY)
      carrying terminal deletion of the chromosome 4 (q31qter) segment resulting in
      craniofacial dysmorphism, skeletal anomalies, ocular findings and cardiac defect.

PMID- 24032294
TI  - Associated malformations among infants with radial ray deficiency.
AB  - Infants with radial ray deficiencies very often have other associated congenital
      anomalies. The reported frequency and types of associated malformations vary
      between different studies. The purpose of this investigation was to assess the
      frequency and types of associated malformations among infants with radial ray
      deficiencies in a geographically well-defined population from 1979 to 2004 of
      346,831 consecutive births. Of the 73 infants with radial ray deficiencies born
      during this period (prevalence at birth of 2.1 per 10,000), 75% had associated
      malformations. Infants with associated malformation were divided into
      recognizable conditions (16 (22%) infants with chromosomal and 20 (27%) with non
      chromosomal conditions), and non recognizable conditions (19 (26%) infants with
      multiple malformations). Trisomies 18 and autosomal deletions were the most
      frequent chromosomal abnormalities. VACTERL association, thrombocytopenia absent
      radii syndrome, Fanconi anemia and Holt-Oram syndrome were most often present in
      recognizable non chromosomal conditions. Malformations in the musculoskeletal,
      cardiovascular and urogenital systems were the most common other anomalies in
      infants with multiple malformations and non recognizable conditions. The
      frequency of associated malformations in infants with radial ray deficiencies
      emphasizes the need for a thorough investigation of these infants. Routine
      screening for other malformations especially musculoskeletal, cardiac and
      urogenital systems anomalies may need to be considered in infants with radial ray
      deficiencies, and referral of these infants for genetic evaluation and counseling
      seems warranted.

PMID- 24032295
TI  - Dilated cardiomyopathy in a patient with 22q11.2 microdeletion syndrome.

PMID- 24032296
TI  - Callosotomy in a girl with refractory epilepsy and Smith-Magenis syndrome.

PMID- 24032297
TI  - A boy with cleft palate, hearing impairment, microcephaly, micrognathia and
      psychomotor retardation and a microdeletion in 6p25.3 involving the DUSP22 gene.

PMID- 24032298
TI  - Phacomatosis pigmentovascularis type IIB associated with Sturge-Weber syndrome: a
      case report and review of the literature.

PMID- 24032299
TI  - A new finding in glutaric acidemia type II: dental anomalies.

PMID- 24032300
TI  - The DSM-5 has arrived.

PMID- 24032301
TI  - Japanese Americans' health concerns and depressive symptoms: implications for
      disaster counseling.
AB  - This study examined factors contributing to depressive symptoms among Japanese
      Americans. Data were collected in Houston, Texas, in 2008, before the March 2011
      Japan earthquake, through a community survey including demographic and mental
      health questions and the Hopkins Symptoms Checklist. Among 43 Japanese American
      respondents in this convenience sample, the depression prevalence was 11.6
      percent. Chi-square results found that having anxiety symptoms and holding a
      master's degree had statistically significant relationships with depressive
      symptoms. An independent sample t test found that those having depressive
      symptoms experienced significantly more health issues than those without
      depressive symptoms. When these statistically significant variables were entered
      into a logistic regression model, the overall effect of having health issues,
      anxiety symptoms, and a master's degree collectively predicted depressive
      symptoms. It was also found that Japanese Americans rarely consult mental health
      professionals; in particular, female Japanese American respondents tend to seek
      help from religious leaders. As implied by these findings, the reluctance of
      Japanese Americans to seek formal help can be explained by social stigma, a
      health-oriented approach to treatment, and other cultural considerations.
      Practice implications focus on disaster counseling with a connection between
      mental health needs and health care support.

PMID- 24032302
TI  - Self-injurious behavior in older adults with intellectual disabilities.
AB  - Self-injurious behavior (SIB) is a distressing type of problem behavior that may
      be exhibited in individuals with intellectual disabilities (IDs). This article
      provides an overview of SIB, its underlying causes and functions, as well as
      other key variables associated with its manifestation. Adults with IDs are
      routinely living longer. Given this rapidly emerging and expanding population,
      special attention is given to SIB in aging adults with IDs that may result from
      age-related risk factors. Risks include increasing and unresolved health issues,
      physical changes, declining physical abilities, transitions to new residential
      environments, and the potential for experiencing loss and bereavement. The
      article concludes with practice implications for social workers who may encounter
      older individuals with IDs and SIB.

PMID- 24032303
TI  - Implicit spiritual assessment: an alternative approach for assessing client
      spirituality.
AB  - To provide optimal services, a spiritual assessment is often administered to
      understand the intersection between clients' spirituality and service provision.
      Traditional assessment approaches, however, may be ineffective with clients who
      are uncomfortable with spiritual language or who are otherwise hesitant to
      discuss spirituality overtly. This article orients readers to an implicit
      spiritual assessment, an alternative approach that may be more valid with such
      clients. The process of administering an implicit assessment is discussed, sample
      questions are provided to help operationalize this approach, and suggestions are
      offered to integrate an implicit assessment with more traditional assessment
      approaches. By using terminology that is implicitly spiritual in nature, an
      implicit assessment enables practitioners to identify and operationalize
      dimensions of clients' experience that may be critical to effective service
      provision but would otherwise be overlooked.

PMID- 24032304
TI  - Recognizing new opportunities: reconceptualizing policy advocacy in everyday
      organizational practice.
AB  - Policy advocacy is a concept that is of both practical and historical importance
      to the profession of social work. To keep up with developments in how advocacy is
      practiced at the ground level, however, social work research on advocacy needs to
      expand in scope. Changes in government contracting and public management
      practices have reshaped the opportunity structure for policy advocacy,
      incentivizing a kind of advocacy that is routine, professionalized, and
      collaborative. At the same time, these practices have raised questions about
      democratic representation and the degree to which social work advocacy adequately
      reflects client concerns. This article presents a model for how policy advocacy
      can be usefully reconceptualized to account for changes in the policy and funding
      environment and concludes by suggesting ways that social work research and theory
      can better reflect practice realities.

PMID- 24032305
TI  - The effect of prenatal and postnatal care on childhood obesity.
AB  - Childhood obesity continues to be a major public health problem in the United
      States. If this problem is unresolved, some children will be at risk for
      disorders such as type 2 diabetes, high blood pressure, and cancer and will
      become a high economic and social burden for society. Using the National
      Longitudinal Survey of Youth, Child and Young Adult sample (N = 6,643), this
      study examined the relationship between the effect of pre- and postnatal
      characteristics and obesity. The findings of this study show that the probability
      of childhood obesity can be lessened if pregnant women do not smoke and do not
      gain significant pregnancy-related weight. Moreover, breast feeding and health
      insurance were also found to be correlated to avoiding childhood obesity.

PMID- 24032306
TI  - School-based social work interventions: a cross-national systematic review.
AB  - Across the globe, social workers serve schools in a variety of capacities,
      providing services such as skills training; individual, group, and family
      counseling; crisis intervention; home visits; parent support and education; and
      advocacy for students, families, and school systems. To date, no synthesis of the
      literature exists examining tier 1 and tier 2 cross-national school-based social
      work interventions. Therefore, the purpose of this systematic review was twofold:
      (1) to identify tier 1 and tier 2 school-based interventions that involve social
      workers and (2) to examine the extent to which the interventions are efficacious
      with school-based youths. A computerized search with inclusion and exclusion
      criteria was conducted using several databases. Eighteen studies were included
      for the final sample in this review. Effect sizes were calculated for all
      outcomes to determine magnitude of treatment effect. Results indicated that most
      of the studies were conducted in the United States (n = 14) and half (n = 9) of
      the included interventions were tier 1. Many positive effect sizes were found.
      Interventions aimed to treat a variety of outcomes such as sexual health,
      aggression, self-esteem, school attendance, identity, and depression. More
      research is needed to determine the effectiveness of school-based social work
      worldwide.

PMID- 24032307
TI  - Caregivers' moral narratives of their African American children's out-of-school
      suspensions: implications for effective family-school collaborations.
AB  - In this qualitative study, the authors examined the culturally nuanced meanings
      of out-of-school suspensions for 30 lower income caregivers of African American
      children suspended from school. Caregivers were invited to describe their
      experiences of their children's suspensions during in-depth, individual,
      audiotaped interviews. Caregivers generally valued their children's school
      success, recognized when their children had misbehaved, and supported educators'
      imposition of appropriate consequences. Out-of-school suspensions, however, were
      rarely viewed as appropriate consequences. On the contrary, caregivers produced
      emotionally laden moral narratives that generally characterized their children's
      suspensions as unjust; harmful to children; negligent in helping children with
      underlying problems such as bullying; undermining parents' racial socialization;
      and, in general, racially problematic. Suspensions also contributed to some
      families' withdrawal from participation in their schools. Understanding how
      caregivers experience children's out-of-school suspensions provides important
      clues to how families and schools can work together to effectively reduce racial
      disparities in out-of-school suspensions.

PMID- 24032308
TI  - Resolving social problems associated with sexuality: can a "sex-positive"
      approach help?

PMID- 24032309
TI  - The DSM-5 and the bereavement exclusion: a call for critical evaluation.

PMID- 24032310
TI  - Passport biopsies: hospital deportations and implications for social work.

PMID- 24032311
TI  - Margaret Sanger and the Nazis: how many degrees of separation?

PMID- 24032312
TI  - [Motives and wishes to adopt children in a social change: results of a
      longitudinal view].
AB  - 150 files of adopted children chosen from the archive of the protestant
      association for adopted and foster children in Duesseldorf-Wittlaer, being
      mediated to families between 1947 and 1987, were evaluated with a special
      evaluation document, regarding the motives and wishes to adopt children. The
      results indicate that the expectation of adoptive parents of their potential
      adopted child has changed essentially during the period that was regarded.
      Possible causes could be norms and values being in a social and historical
      change, but also changes in the adoption processes.

PMID- 24032313
TI  - [Diagnostic of ADHD in childhood and adolescence with the K-SADS-PL].
AB  - Attention Deficit-/Hyperactivity Disorder (ADHD) is one of the most prevalent
      psychiatric disorders in childhood and adolescence, often accompanied by comorbid
      disorders. A high standard of diagnostic assessment combined with a demand for
      valid diagnostic instruments is necessary. The K-SADS-PL is an established semi
      structured interview, focusing on the categorical assessment of psychiatric
      disorders. The aim of the following study was to examine specific characteristics
      of ADHD symptomatology including functional and behavioral assessment. Therefore
      correlations between the result in a diagnostic interview (K-SADS-PL) and
      different ADHD-specific instruments were performed. Groups were formed (exposed
      vs. unexposed), based on the diagnostic finding in the K-SADS-PL. Group-specific
      test score differences were calculated and compared by multivariate analyses of
      covariance. Children with ADHD showed a significantly higher impact of conduct
      and emotional problems than the unexposed group. Health related quality of life
      was more impaired in children and families suffering from ADHD which refers to
      the relevance of family-oriented psychotherapy.

PMID- 24032314
TI  - [How children who's siblings are diagnosed with cancer experience and regulate
      the disease].
AB  - The aim of this study is to investigate behaviour problems and emotional
      regulation of children who's siblings are diagnosed with cancer. Participants
      were assessed with the Strengths and Difficulties Questionnaire (SDQ) and the
      MacArthur Story Stem Battery (MSSB). Both instruments were administered twice
      (shortly after diagnosis and at the end of treatment). Brothers and sisters of 14
      children suffering from cancer were compared with 18 siblings of healthy
      individuals. In the SDQ no differences between the two groups were found. At time
      1 the MSSB showed significant differences in number and quality of displayed
      contents, representation of parents and the way of performing the narrative. At
      time 2 narratives changed particularly in the treatment group, but some
      differences still remained. Overall siblings of children suffering from cancer
      showed more intrapsychic reaction to the disease than became obvious in their
      behaviour. This fosters the conclusion that there may be a need for specific
      support for siblings of children with cancer in order to prevent them from
      psychic disorders and pathological mourning reactions.

PMID- 24032315
TI  - [Mental disorders in adolescence: current trends in therapy].
AB  - On the basis of the high prevalence for behavioural problems and mental disorders
      in adolescence and its persistence into adulthood it is tested whether and based
      upon which emphasis this topic is considered in the recent discussion on
      psychotherapy. Therefore, a bibliometric analysis is given that summarizes the
      issue in the 2011 and 2012 volumes of representative German child and adolescent
      psychological and psychiatric journals. The focus lies on conduct disorder,
      depression, deliberate self-harm, dissociative disorder, and post traumatic
      stress disorder.

PMID- 24032316
TI  - Native reading direction and corresponding preferences for left- or right-lit
      images.
AB  - The first language an individual learns has been shown to influence performance
      on cognitive tasks. Individuals who first learn to read and write in a left-to
      right direction (native left-to-right readers) tend to bisect lines left of
      centre and draw counterclockwise circles, whereas those who learn to read and
      write from right-to-left (native right-to-left readers) will bisect lines closer
      to the objective centre and draw circles in a clockwise direction. The aim of the
      current study was to assess group differences in image preferences and eye
      movements when participants are simultaneously presented with an original and
      mirror image with an obvious illumination difference. Twenty native left-to-right
      readers (4 men, 16 women) and 25 native right-to-left readers (13 men, 12 women)
      participated. Left-to-right readers made more fixations on the left side of
      images and exhibited a significantly different left-lit image bias than right-to
      left readers' choices. These results draw attention to the influence that reading
      direction has on scanning distributions and lighting preferences, and question
      previous results finding no difference between groups.

PMID- 24032317
TI  - A preliminary assessment of the reliability and validity of a computerized
      working memory task.
AB  - The aim of the current study was to evaluate the psychometric properties of a
      recently developed measure of working memory: the Double Span Task. The Double
      Span Task is the first experimental task designed to assess all three components
      of Baddeley's (1992) model of working memory. The reliability of the Double Span
      Task was assessed in a sample of 105 older adults (M age = 64.3 yr., SD = 6.4).
      The internal consistency and test-retest reliability of the Double Span Task were
      good. The validity of the Double Span Task was assessed using a different sample
      of 49 older adults (M age = 70.0 yr., SD = 9.3). Performance on the Double Span
      Task was positively correlated with performance on a well-established measure of
      working memory, the Letter Number Sequencing Task. The Double Span Task also
      showed good discriminant validity. The Double Span Task is a reliable and valid
      measure of all three components of the working memory system.

PMID- 24032318
TI  - Age and gestural differences in the ease of rotating a virtual 3D image on a
      large, multi-touch screen.
AB  - Providing a natural mapping between multi-touch gestures and manipulations of
      digital content is important for user-friendly interfaces. Although there are
      some guidelines for 2D digital content available in the literature, a guideline
      for manipulation of 3D content has yet to be developed. In this research, two
      sets of gestures were developed for experiments in the ease of manipulating 3D
      content on a touchscreen. As there typically are large differences between age
      groups in the ease of learning new interfaces, we compared a group of adults with
      a group of children. Each person carried out three tasks linked to rotating the
      digital model of a green turtle to inspect major characteristics of its body.
      Task completion time, subjective evaluations, and gesture changing frequency were
      measured. Results showed that using the conventional gestures for 2D object
      rotation was not appropriate in the 3D environment. Gestures that required
      multiple touch points hampered the real-time visibility of rotational effects on
      a large screen. While the cumulative effects of 3D rotations became complicated
      after intensive operations, simpler gestures facilitated the mapping between 2D
      control movements and 3D content displays. For rotation in Cartesian coordinates,
      moving one fingertip horizontally or vertically on a 2D touchscreen corresponded
      to the rotation angles of two axes for 3D content, while the relative movement
      between two fingertips was used to control the rotation angleof the third axis.
      Based on behavior analysis, adults and children differed in the diversity of
      gesture types and in the touch points with respect to the object's contours.
      Offering a robust mechanism for gestural inputs is necessary for universal
      control of such a system.

PMID- 24032319
TI  - Effects of position and task demands on endogenous eyeblink.
AB  - The present study investigated the effects of the supine position and task
      demands on blink activities. 24 participants (M age = 21.7 yr., SD = 0.5)
      performed the Japanese version of the Reading Span Test to investigate the
      effects of task difficulty. Eyeblink activities were detected by
      electrooculogram, via a wireless system, and were analyzed using newly developed
      software. Results showed that the supine position did not affect blink rate
      itself, but some wave characteristics of blinks, such as blink amplitude and
      closing and re-opening duration, were influenced; specifically, amplitude was
      reduced and durations increased. Further analyses suggested that task demands
      affected eyeblink rates but did not affect waveform attributes. Eyeblink rates
      increased during task performance and decreased during rest periods but it was
      not confirmed that this task demand effect was larger in the supine position than
      in the sitting position.

PMID- 24032320
TI  - Second language listening difficulties perceived by low-level learners.
AB  - The purpose was the develop a questionnaire to identify the specific listening
      difficulties of second language (L2) learners. Based on previous research, a
      questionnaire containing 31 items was developed and administered to 1,056 college
      freshmen. The whole sample was split randomly into two subsamples, each
      containing 528 cases. Exploratory factor analysis was performed to analyse the
      first subsample, and six factors were extracted, explaining a total of 57.1% of
      variance. To test the factor model, confirmatory factor analysis was conducted
      with the second subsample. Various fit indices were examined. The best fitting
      model for the data was a 23-item, six-factor model representing text, input
      channel and surroundings, relevance, listener, speaker, and task. Apart from the
      listener factor, all components are external ones and deemed to be uncontrollable
      by listeners. L2 learners must take an active role in listening practice to
      overcome L2 listening difficulties.

PMID- 24032321
TI  - Effect of color contrast on visual lobe shape characteristics.
AB  - This study examined the effects of the color contrast of target and background
      objects on visual lobe area and shape characteristics. For visual lobe mapping
      the participants had to locate a single colour target amongst a homogeneous
      background of non-targets during a brief presentation. Targets of six different
      colors (red, yellow, green, cyan, blue, purple) were tested, the non-targets were
      black and the background was metallic grey. The results showed that color
      contrast did not affect visual lobe parameters under the constant luminance
      contrast condition of 6:1 tested in the experiment. Subjective preference
      evaluations showed that the blue and purple targets resulted in the highest
      visual comfort and overall preference, respectively, while the yellow target was
      the most negatively rated. The color preferences here were somewhat different
      from the previous color combination studies. It might be due in part to the
      constant luminance contrast and display polarity used here.

PMID- 24032322
TI  - Evaluation of an automated procedure for detecting frequency-following responses
      in American and Chinese neonates.
AB  - To date, observations of the scalp-recorded frequency-following response (FFR) to
      voice pitch have depended on subjective interpretation of the experimenter. The
      purpose of this study was to develop and evaluate an automated procedure for
      detecting the presence of a response. Twenty American (9 boys, 1-3 days) and 20
      Chinese (10 boys, 1-3 days) neonates were recruited. A Chinese monosyllable that
      mimicked the English vowel /i/ with a rising pitch (117-166 Hz) was used as the
      stimulus. Three objective indices (Frequency Error, Tracking Accuracy, and Pitch
      Strength) were computed from the recorded brain waves and the test results were
      compared with human judgments to calculate the sensitivity and specificity
      values. Results demonstrated that the automated procedure produced sensitivity
      values between 53-90% and specificity values between 80-100%, and could be used
      to assess the presence of an FFR for neonates who were born in a tonal or non
      tonal language environment.

PMID- 24032323
TI  - An implicit assessment of the effect of artificial cheek raising: when your face
      smiles, the world looks nicer.
AB  - Experiments were conducted with 80 undergraduate participants (52 men and 28
      women) to examine whether the sensation of having the cheeks lifted or pulled
      down would elicit different responses in an implicit association test. Implicit
      emotional responses were measured for two facial feedback conditions by utilizing
      a modified Affect Misattribution Procedure. The participants wore one of two
      types of simple devices designed to either raise or lower the cheeks, and rated
      neutral targets preceded by three types (positive, neutral, or negative) of prime
      photos. The results showed that the participants whose cheeks were raised tended
      to rate the targets statistically more positively than did those whose cheeks
      were lowered.

PMID- 24032324
TI  - The effect of interior aircraft noise on pilot performance.
AB  - This study examined the effect of the interior sounds of an aircraft cockpit on
      ratings of affect and expected performance decrement. While exposed to 12
      interior aircraft sounds, of which half were modified to correspond to what is
      experienced with an active noise reduction (ANR) headset, 23 participants rated
      their affective reactions and how they believed their performance on various
      tasks would be affected. The results suggest that implementation of ANR-technique
      has a positive effect on ratings of expected performance. In addition, affective
      reactions to the noise are related to ratings of expected performance. The
      implications of these findings for both research and pilot performance are
      discussed.

PMID- 24032325
TI  - Context is quick, knowledge is slow: rapid time-course of contextual modulations
      in the horizontal-vertical illusion.
AB  - One of the oldest visual illusions consists of observers' tendency to estimate
      vertical lines as longer than equal horizontal lines. This Horizontal-Vertical
      Illusion has been studied widely; however, most studies may not generalize to
      natural contexts because they have not addressed the low-level processes that
      occur rapidly and in response to context-free lines vs the possibility for high
      level processes that arise over time in response to context. These issues were
      investigated via a novel design: rapid time-sequencing embedded within the
      context of natural images. Participants saw different levels of context and the
      Horizontal-Vertical Illusion was measured. In traditional Horizontal-Vertical
      Illusion displays without natural context, there was a robust invariance of the
      illusion to stimulus duration. Within context, however, there was strong
      modulation: the magnitude of the illusion decreased by over 50% or increased over
      30%, depending upon placement within context. Knowledge of object properties such
      as size or line length did not account for this effect. It appears that previous
      domain-general investigations of the Horizontal-Vertical Illusion did not address
      the specific higher-order processes that produce the illusion in natural
      contexts.

PMID- 24032326
TI  - A comparison of Hispanic middle school students' performance, and perceived and
      actual physical exertion, on the traditional and treadmill one-mile runs.
AB  - The purpose of this study was to assess whether a treadmill mile is an acceptable
      FitnessGram Test substitute for the traditional one-mile run for middle school
      boys and girls. Peak heart rate and perceived physical exertion of the
      participants were also measured to assess students' effort. 48 boys and 40 girls
      participated, with approximately 85% classified as Hispanic. Boys' mean time for
      the traditional one-mile run, as well as peak heart rate and perceived exertion,
      were statistically significantly faster and higher, respectively, than for the
      treadmill mile. Girls' treadmill mile times were not statistically significantly
      different from the traditional one-mile run. There were no statistically
      significant differences for girl's peak heart rate or perceived exertion. The
      results suggest that providing middle school students a choice of completing the
      FitnessGram mile run in either traditional one-mile run or treadmill one-mile
      format may positively affect performance.

PMID- 24032327
TI  - Does verbal and gestural expression ability predict comprehension ability in
      cerebral palsy?
AB  - Some people with cerebral palsy have motor and associated impairments that may
      hinder verbal and gestural expression to various extents. This study explores
      whether the ability to produce verbal or gestural expressions may be related to
      the comprehension of verbal communications and gestures. The influence of
      severity of motor impairment, general cognitive performance, and age on
      comprehension ability was also explored. Forty people with cerebral palsy were
      assigned to different groups according to their verbal and gestural expression
      abilities. A neuropsychological assessment of comprehension abilities and general
      cognitive performance was carried out. Multiple linear regression analysis was
      applied to identify the possible influence of expression abilities on
      comprehension abilities and also to detect the possible contribution of severity
      of motor impairment, general cognitive performance, and age. Results indicate
      that verbal and gestural comprehension was mainly predicted by general cognitive
      performance. Severity of motor impairment and age did not contribute to
      predicting comprehension abilities. Only verbal grammar comprehension was
      significantly predicted by verbal expression ability. Verbal expression ability
      may be an important marker for cerebral palsy therapies. In non-ambulant patients
      with bilateral cerebral palsy, impaired gestural expression should not be taken
      as an indicator of impaired gestural comprehension.

PMID- 24032328
TI  - Atypical caudate anatomy in children who stutter.
AB  - A temporal motor defect in speech preparation and/or planning may contribute to
      the development of stuttering. This defect may be linked to a dysfunctional
      cortical-subcortical network at the level of the striatum. To determine whether
      structural differences exist and whether group differences are associated with
      stuttering severity or manual laterality, the caudate was measured in 14 children
      who stutter (CWS) and in a control group of right-handed boys, ages 8-13 years.
      There was a statistically significant hemisphere by group effect for caudate
      volume. CWS had reduced right caudate volume and atypical leftward asymmetry
      compared to controls. Nine of the 13 CWS with atypical caudate asymmetry had
      atypical manual laterality. These anomalies may represent a vulnerability that
      perturbs speech planning/preparation and contributes to inefficiencies in action
      perception coupling that may be an indicator of stuttering susceptibility. These
      results suggest that right-handed boys who stutter may have a defect in the
      feedforward cortico-striato-thalamo-cortical networks.

PMID- 24032329
TI  - Chronic pain effect on body schema and neuropsychological performance in
      athletes: a pilot study.
AB  - The ability to recognize the body parts blindfolded is called body schema.
      Chronic pain disrupts cognitive function and could lead to an altered body
      schema. Commonly competitive athletes have chronic pain, but still train and
      compete. The goal of this study was to assess the body schema of competitive
      athletes with chronic pain. Pain was measured with the McGill Pain Questionnaire.
      To assess the body schema, the Image Marking Procedure was used to assess the
      capacity of the participants to project their bodies in space. Neuropsychological
      performance was assessed with the Grooved Pegboard Test. There was no difference
      in body schema between groups; neuropsychological performance indicated better
      scores in the athlete group. This study showed that despite chronic pain, the
      athlete group presented unaltered body schema and better neuropsychological
      performance, perhaps explained by self-selection.

PMID- 24032330
TI  - Postural stability during one-leg stance on an unstable moving platform and its
      relationship with each leg.
AB  - This study examined the laterality of the supporting leg in postural stability
      during a one-leg stance test on an unstable moving platform and its practice
      effect. 30 male university students were evaluated using the omnidirection
      stability index (OSI) during a one-leg stance test on an unstable moving platform
      (three trials). The leg used when kicking a ball was defined as the manipulation
      leg (ML) and the supporting leg was defined as the non-manipulation leg (NML).
      According to the two-way repeated measures analysis of variance (ANOVA; trials x
      legs), a statistically significant difference was observed only on the leg
      factor, and OSI values of the second and third trials were less for the ML than
      the NML. The correlation between both legs was statistically significant but not
      high. The ML was superior to NML with regard to stability, and no practice effect
      with trials was evident in either leg.

PMID- 24032331
TI  - Posturography characteristics of obese children with and without associated
      disorders.
AB  - A group of 59 obese children ages 6-12 years were interviewed for current medical
      diagnoses (e.g., Attention Deficit Hyperactivity Disorder- ADHD, and clumsiness)
      and later were examined posturographically for balance and stability. General
      stability of all the obese children deviated significantly from norms. 32.2% of
      the obese children had a pattern of balance that could indicate orthopedic
      problems. Obese children with ADHD or perceived clumsiness had significantly
      worse balance and postural performance compared to other obese children. Balance
      and posture among obese children without suspicion of problems were similar to
      non-obese controls. In conclusion, obese children with associated disorders (such
      as ADHD and perceived clumsiness) manifested disturbance in balance control.
      Thus, physical activity interventions for these children should include safety
      measures to decrease the chances of falling and subsequent injury.

PMID- 24032332
TI  - Peak torque and electromyographic responses during fatiguing concentric muscle
      actions with eyes-open versus eyes-closed.
AB  - This study compared peak torque and electromyographic (EMG) mean frequency
      responses during fatiguing muscle actions with eyes-open vs eyes-closed. On four
      separate days, 21 men (M age = 23 yr.) performed 100 repeated maximal concentric
      muscle actions of the forearm flexors with eyes-open, eyes-closed, eyes-closed
      for first 50 muscle actions, and eyes-closed for the last 50 muscle actions while
      surface EMG signals were collected from the biceps brachii. The data were
      examined with seven separate repeated measures analyses of variance. There were
      no mean differences among the conditions for initial, average, and final peak
      torque, percent decline, the linear slope coefficient for the decline in peak
      torque, as well as the linear slope coefficient and y-intercept for the
      normalized EMG mean frequency vs repetition number relationships. These findings
      indicate performance during fatiguing muscle actions is not influenced by whether
      participants have their eyes open or closed throughout testing.

PMID- 24032333
TI  - Effects of a short-term coordination exercise program during school recess:
      agility of seven- to eight-year-old elementary school children.
AB  - This study tested the effect of a short-term coordination program focused on
      improving the agility of school children ages 7 to 8 years. Healthy Japanese
      children were placed in an experimental group of 26 children (10 girls, 16 boys)
      and a control group of 20 children (9 girls, 11 boys). The experimental group
      participated in 10 coordination program sessions during recesses; each session
      was performed 1 to 3 times per week, for 26 days. No differences were observed
      between the groups in repeated side-step scores prior to the program, although an
      interaction was observed after the completion of the treatment. The short-term
      coordination program was effective in increasing the agility of elementary school
      children aged 7 to 8 years.

PMID- 24032334
TI  - Blocked and alternating variable practice and unintended spatial variations in
      continuous aiming movements.
AB  - The main goal of the study was to test a prediction of schema theory: a wider
      range of variable practice would result in better transfer performance compared
      to a narrower range of variable practice in less-studied, continuous aiming
      movements. Constant and variable amplitude continuous aiming movements were
      investigated in the preferred hand of participants of college age (N = 32; 8 men,
      24 women). Participants made continuous rapid reversal movements with a lever in
      the horizontal plane. Groups attempted to reach a short (20 degrees) target and a
      long target (either 45 degrees or 70 degrees) in separate constant-practice
      conditions, but alternated between the two targets in a variable practice
      condition. On the transfer test, participants alternated between unpracticed 10
      degrees and 80 degrees targets. Four blocks of practice trials were provided in
      each condition, with 20 movements made in each. Movements were more accurate and
      consistent during constant practice compared to variable practice, with the 20
      degrees-70 degrees group having greater spatial errors compared to the 20 degrees
      45 degrees group. Both groups performed equally well on the novel transfer test
      suggesting that adequate practice variability had been provided during
      acquisition.

PMID- 24032335
TI  - Disturbance in hitting accuracy by professional and collegiate baseball players
      due to intentional change of target position.
AB  - The present study investigated bat control of skilled baseball batters during tee
      batting, faced with an intentional change in target position. Twelve, skilled,
      male baseball players (M age = 24 yr., SD = 4) participated in the study.
      Participants were instructed to hit a baseball off a tee 0.8 m from the ground
      (Hitting condition), and also to deliberately swing just above the ball (Air
      Swing condition). The task for the participants was to perform, in alternate
      order, 15 swings at a real baseball on a stationary tee and 15 swings at an
      imaginary ball that was said to be on top of the real baseball. The participants
      were instructed to hit the ball toward center field just as they would hit in a
      game. While most participants could hit the real ball in the sweet area of the
      bat, only one participant did so in the Air Swing condition. Average distances
      from the center of the sweet area to ball center at the moment of ball-bat
      contact in the Air Swing condition (85 mm) were significantly greater than the
      distance in the Hitting condition (38 mm). The larger error in hitting an
      imaginary ball in the sweet area could be due to perceptual changes following the
      batter's altered focus, expectation of a lack of contact, and/or lack of feedback
      from the swing. It was suggested that baseball batters should be aware of the
      possible error in hitting accurately when they intentionally shifted the target.

PMID- 24032336
TI  - Sex-related trends in participation and performance in the 'Swiss Bike Masters'
      from 1994-2012.
AB  - General participation in contests such as ultra-marathons and ultra-triathlons
      has increased considerably over the past 30 years, especially among women. This
      study investigated performance trends in the Swiss Bike Masters, one of the first
      and most prestigious mountain bike, ultra-endurance races in its class, with
      comparisons of participation and performance trends to similar races. The
      development of performance in the Swiss Bike Masters held between 1994 and 2012
      was investigated by analysing the number of finishers, their age, sex, and
      cycling speed. Between 1994 and 2009, the athletes had to cover 120 kilometers
      with a total difference in altitude of 5,000 meters. Since 2010, the race
      distance was shortened to 105 kilometers and the total difference in altitude was
      reduced to 4,400 meters. The total men participating and total finishing
      decreased significantly, while women's participation has remained low. The age of
      the annual winners and the annual top three finishers showed no changes over
      time. Performances of the annual fastest women improved, while performances of
      the annual fastest men remained unchanged. To summarize, rate of finishing has
      decreased for men and has been stable, but low, among women. The sex difference
      in cycling speed for the best cyclists has decreased across the years.

PMID- 24032337
TI  - Predictive importance of anthropometric and training data in recreational male
      Ironman triathletes and marathon runners: comment on the study by Gianoli, et al.
      (2012).
AB  - Anthropometric and training data have been reported as statistically significant
      predictors of race performance in endurance events. However, it is well
      established that physiological characteristics, i.e., maximal oxygen uptake
      (VO2max), the use of a high percentage of VO2max during sustained exercise, and
      work efficiency are predominant predictors of performance in those events. Thus,
      the essential issue is whether the anthropometric and training data give
      additional predictive power beyond these other measures.

PMID- 24032338
TI  - Effect of a moderate-intensity aerobic exercise on estimates of egocentric
      distance.
AB  - The goal was to explore the effect of a moderate-intensity exercise on egocentric
      distance estimates (the distance between the participant and an object in space)
      in physically trained and untrained participants (N = 54), divided into three
      groups of 18 national-level soccer players, 18 sedentary people, and 18 controls.
      Participants engaged in a distance estimation task at rest, and also while
      pedalling on an ergocycle for 10 min. at 60% of the maximal aerobic intensity.
      Estimates were recorded during pre-exercise, stability Phase 1 (between the 1st
      and the 2nd min. of exercise), Phase 2 (5th to 6th min.), Phase 3, (9th to 10th
      min.), and immediately after the exercise. Estimates of egocentric distance were
      more accurate in trained than untrained participants. Perception improved during
      and after the exercise in comparison with pre-exercise. In addition, the group x
      exercise interaction indi- cated estimation improved during and after exercise,
      with more accuracy in the trained than untrained participants. Fitness and
      moderate aerobic exercise improve the egocentric distance estimation in humans.

PMID- 24032339
TI  - Attentional processes and choking under pressure.
AB  - The self-focus theory of choking under pressure explains decreases in performance
      of well-learned motor tasks with an increase in skill-focused attention. This
      shift in attentional focus has been demonstrated; however, specific propositions
      about the processes in pressure-induced attentional shift are yet to be
      developed. This study assesses whether specific aspects of movement execution
      attract more attention than others when movements are executed under pressure.
      Such elements are important in conscious movement control before execution
      becomes automated through practice; under pressure, attention may be redirected
      to these elements. Basketball free throws were executed by 22 junior national
      team members in a low and high pressure situation. Two dual task/focus conditions
      (related to different aspects of the movement) were implemented in each pressure
      condition. This dual task paradigm was used as a direct and detailed measure of
      skill focused attention, suitable to show specific pressure induced shifts of
      attention that lead to performance decrements. Pressure was induced by telling
      players that their performance would be evaluated by coaches. Players were
      defined as chokers if their performance decreased under this pressure. Chokers
      showed differences with regard to their attentional focus on movement execution
      in the pressure conditions compared to the players defined as non-chokers. The
      findings suggest that attentional shifts during choking can be related to
      specific aspects of movement execution.

PMID- 24032340
TI  - Sex differences in ultra-triathlon performance at increasing race distance.
AB  - It has been argued that women should be able to outrun men in ultra-endurance
      distances. The present study investigated the sex difference in overall race
      times and split times between elite female and male Ironman triathletes competing
      in Ironman Hawaii (3.8 km swimming, 180 km cycling, and 42.195 km running) and
      Double Iron ultra-triathletes (7.6 km swimming, 360 km cycling, and 84.4 km
      running). Data from 20,638 athletes, including 5,163 women and 15,475 men
      competing in Ironman Hawaii and from 143 women and 1,252 men competing in Double
      Iron ultra-triathlon races held worldwide between 1999 and 2011 were analyzed. In
      Ironman Hawaii, the sex difference in performance of the top three athletes
      remained unchanged during the period studied for overall race time. For Double
      Iron ultra-triathletes, the sex difference for the top three athletes remained
      unchanged for overall race time. Sex differences increased as endurance race
      distances increased and showed no changes over time. It appears that women are
      unlikely to close the gap in ultra-endurance performance with men in ultra
      triathlons in the near future. Physiological (e.g., maximum oxygen uptake) and
      anthropometric characteristics (e.g., skeletal muscle mass) may set biological
      limits for women.

PMID- 24032341
TI  - Toward a synthesis of hirsutellone B by the concept of double cyclization.
AB  - This account describes a strategy for directly forming three of the six rings
      found in the polyketide natural product hirsutellone B via a novel cyclization
      cascade. The key step in our approach comprises two transformations: a large-ring
      forming, nucleophilic capture of a transient acylketene and an intramolecular
      Diels-Alder reaction, both of which occur in tandem through thermolyses of
      appropriately functionalized, polyunsaturated dioxinones. These thermally induced
      "double cyclization" cascades generate three new bonds, four contiguous
      stereocenters, and a significant fraction of the polycyclic architecture of
      hirsutellone B. The advanced macrolactam and macrolactone intermediates that were
      synthesized by this process possess key features of the hirsutellone framework,
      including the stereochemically dense decahydrofluorene core and the strained para
      cyclophane ring. However, attempts to complete the carbon skeleton of
      hirsutellone B via transannular carbon-carbon bond formation were undermined by
      competitive O-alkylation reactions. This account also documents how we adapted to
      this undesired outcome through an evaluation of several distinct strategies for
      synthesis, as well as our eventual achievement of a formal total synthesis of
      hirsutellone B. 

PMID- 24032342
TI  - The Spanish linguistic validation of the ureteral stent symptom questionnaire.
AB  - BACKGROUND AND PURPOSE: Ureteral Stent Symptoms Questionnaire (USSQ) is an
      intervention-specific health-related quality-of-life (HrQoL) measure. We describe
      development and validation of the Spanish version. MATERIALS AND METHODS: We
      followed established methods to develop the Spanish version of the original USSQ.
      After pilot testing, we conducted a formal validation study; 70 patients,
      undergoing placement of ureteral stents, successfully completed the Spanish USSQ
      as well as the EuroQoL-5D (male and female), the ICIQ male and female lower
      urinary tract symptoms questionnaires at weeks 1 and 4 after stent insertions,
      and at week 4 after their removal. In addition, 40 healthy people acted as a
      control group and completed the same questionnaires twice at 3-week intervals.
      Statistical analyses were performed to evaluate reliability, validity, and
      sensitivity to change of the Spanish USSQ. RESULTS: After revision of the initial
      two drafts after translation, back translation, and pilot testing, a final draft
      was developed that underwent field testing. Psychometric analyses revealed
      satisfactory internal consistencies (Cronbach alpha coefficients: 0.73-0. 85) and
      test-retest reliability (Spearman correlation coefficient: >0.6) for the domains
      of urinary symptom, body pain, and general health. It demonstrated satisfactory
      discriminant validity (sensitivity to change, p<0.01), convergent validity (good
      correlations between the domains of the USSQ and existing validated
      questionnaires), and test-retest reliability (p<0.001). Analysis of the domains
      of the sexual matter (21.4%) and work performance (35.7%) were limited because of
      the small proportion of the study population for whom it was applicable.
      CONCLUSIONS: Results of our development and validation study demonstrate that the
      new Spanish version of the USSQ is a psychometrically valid intervention-specific
      measurer for use in the second most common language in the world. It is a
      reliable outcome measure that could be used for both clinical and research
      purposes.

PMID- 24032343
TI  - Paediatric essential thrombocythaemia: clinical and molecular features, diagnosis
      and treatment.
AB  - The incidence of essential thrombocythaemia (ET) in children (age <=18 years) is
      extremely low. The natural course of the disorder in children has not been
      clarified. The rarity of patients and the variability of tested parameters make
      it difficult to draw any definitive conclusion in pathogenesis and diagnosis of
      paediatric ET. What makes the onset of thrombocytosis earlier in children is
      still uncertain. A diagnostic algorithm for paediatric ET has not been
      established, and current risk stratification used to guide therapeutic decisions
      in adults has not been validated in children. Vascular complications and
      transformation to myelofibrosis and leukaemia in this special entity have been
      reported, suggesting that ET in children is not an entirely benign disease. The
      crucial question is how to identify patients who are at high risk of
      complications and need treatment. There are insufficient data to recommend a
      specific agent in children. The purpose of this review is to outline the most
      recent progress in paediatric ET and to help with understanding the clinical
      course, molecular features, diagnosis and treatment strategies in this special
      group. 

PMID- 24032344
TI  - Degradable and comb-like PEG-based copolymers by nitroxide-mediated radical ring
      opening polymerization.
AB  - Three cyclic ketene acetals, 2-methylene-1,3-dioxepane (MDO), 5,6-benzo-2
      methylene-1,3-dioxepane (BMDO), and 2-methylene-4-phenyl-1,3-dioxolane (MPDL),
      have been copolymerized with oligo(ethylene glycol) methyl ether methacrylate and
      a small amount of acrylonitrile (or styrene) at 90  degrees C by
      nitroxidemediated radical ring-opening polymerization, as a convenient way to
      prepare degradable PEG-based copolymers for biomedical applications. MPDL was the
      best candidate, enabling high monomer conversions to be reached and well-defined
      PEG-based copolymers with adjustable amount of ester groups in the main chain to
      be synthesized, leading to nearly complete hydrolytic degradation (5% KOH aqueous
      solution, ambient temperature). The noncytotoxicity of the obtained copolymers
      was shown on three different cell lines (i.e., fibroblasts, endothelial cells and
      macrophages), representing a promising approach for the design of degradable
      precursors for PEGylation and bioconjugation via the NMP technique. 

PMID- 24032345
TI  - One-dimensional palladium wires: influence of molecular changes on supramolecular
      structure.
AB  - Nanostructured materials based on one-dimensional (1D) metal wires are of
      potential utility; however, to date, there is a lack of synthetic methods that
      allow for variation of structure and therefore properties. Here we report the use
      of molecular control elements to alter the solid-state structures of 1D palladium
      wires, including Pd-Pd bond distances and the porosity of the supramolecular
      framework. 

PMID- 24032346
TI  - Theoretical prediction of rare gas containing hydride cations: HRgBF+ (Rg = He,
      Ar, Kr, and Xe).
AB  - The existence of rare-gas-containing hydride ions of boron (HRgBF(+)) has been
      predicted by using ab initio quantum chemical methods. The HRgBF(+) ions are
      obtained by inserting a rare gas (Rg) atom in between the H and B atoms of a
      HBF(+) ion, and the geometries are optimized for minima as well as transition
      states using second-order Moller-Plesset perturbation theory (MP2), density
      functional theory (DFT), and coupled-cluster theory (CCSD(T)) based techniques.
      The predicted HRgBF(+) ions are found to be metastable, and they exhibit a linear
      structure at the minima and a nonlinear planar structure at the transition state,
      corresponding to Cinfinityv and Cs symmetries, respectively. All of the predicted
      HRgBF(+) ions show negative binding energies with respect to the two-body
      dissociation channel, leading to global minima (HBF(+) + Rg) on the singlet
      potential energy surface. In contrast, the dissociation energies corresponding to
      another two-body dissociation channel leading to HRg(+) + BF and two three-body
      dissociation channels corresponding to the dissociation into H + Rg + BF(+) and
      H(+) + Rg + BF show very high positive energies. Apart from positive dissociation
      energies, the predicted ions show finite barrier heights corresponding to the
      transition states involving a H-Rg-B bending mode, leading to the global minima
      products (HBF(+) + Rg). The finite barrier heights in turn would prevent the
      metastable HRgBF(+) species from transforming to global minima products.
      Structure, harmonic vibrational frequencies, stability, and Mulliken and natural
      bonding orbital (NBO) charge distribution values for all of the species are
      reported using the MP2 and DFT methods. Furthermore, the intrinsic reaction
      coordinate analysis confirms that the metastable minimum-energy structure and the
      global minimum products are connected through the corresponding transition state
      for each of the species on the respective singlet potential energy surface. Atoms
      in-molecules (AIM) analysis indicates that the HRgBF(+) ions are best described
      as HRg(+)BF and are analogous to the isoelectronic HRgCO(+) and HRgN2(+) ions.
      The energetic along with charge redistribution and spectroscopic data strongly
      support the possible existence of HRgBF(+) ions. Hence, it might be possible to
      generate HRgBF(+) ions in the DC discharge plasma of a BF3/H2/Rg mixture at low
      temperature, and the predicted ions may be characterized using the magnetic field
      modulated infrared laser spectroscopic technique, which has been used earlier to
      characterize HBF(+) ions. 

PMID- 24032347
TI  - A simple method to measure protein side-chain mobility using NMR chemical shifts.
AB  - Protein side-chain motions are involved in many important biological processes
      including enzymatic catalysis, allosteric regulation, and the mediation of
      protein-protein, protein-DNA, protein-RNA, and protein-cofactor interactions. NMR
      spectroscopy has long been used to provide insights into the motions of side
      chain groups. Currently, the method of choice for studying side-chain dynamics by
      NMR is the measurement of methyl (2)H autorelaxation. Methyl (2)H autorelaxation
      exhibits simple relaxation mechanisms and can be straightforwardly converted to
      meaningful dynamic parameters. However, methyl groups can only be found in 6 of
      19 side-chain bearing amino acids. Consequently, only a sparse assessment of
      protein side-chain dynamics is possible. Therefore, there is a significant
      interest in developing novel methods of studying side-chain motions that can be
      applied to all types of side-chains. Here, we show how side-chain chemical shifts
      can be used to determine the magnitude of fast side-chain motions in proteins.
      The chemical shift method is applicable to all side-chain bearing residues and
      does not require any additional measurements beyond standard NMR experiments for
      backbone and side-chain assignments. 

PMID- 24032348
TI  - Native American ancestry affects the risk for gene methylation in the lungs of
      Hispanic smokers from New Mexico.
AB  - RATIONALE: Gene promoter methylation detected in sputum predicts lung cancer risk
      in smokers. Compared with non-Hispanic whites (NHW), Hispanics have a lower age
      standardized incidence for lung cancer. OBJECTIVES: This study compared the
      methylation prevalence in sputum of NHWs with Hispanics using the Lovelace
      Smokers cohort (n = 1998) and evaluated the effect of Native American ancestry
      (NAA) and diet on biomarkers for lung cancer risk. METHODS: Genetic ancestry was
      estimated using 48 ancestry markers. Diet was assessed by the Harvard University
      Dietary Assessment questionnaire. Methylation of 12 genes was measured in sputum
      using methylation-specific polymerase chain reaction. The association between NAA
      and risk for methylation was assessed using generalized estimating equations. The
      ethnic difference in the association between pack-years and risk for lung cancer
      was assessed in the New Mexico lung cancer study. MEASUREMENTS AND MAIN RESULTS:
      Overall Hispanics had a significantly increased risk for methylation across the
      12 genes analyzed (odds ratio, 1.18; P = 0.007). However, the risk was reduced by
      32% (P = 0.032) in Hispanics with high versus low NAA. In the New Mexico lung
      cancer study, Hispanic non-small cell lung cancer cases have significantly lower
      pack-years than NHW counterparts (P = 0.007). Furthermore, compared with NHW
      smokers, Hispanic smokers had a more rapidly increasing risk for lung cancer as a
      function of pack-years (P = 0.058). CONCLUSIONS: NAA may be an important risk
      modifier for methylation in Hispanic smokers. Smoking intensity may have a
      greater impact on risk for lung cancer in Hispanics compared with NHWs.

PMID- 24032349
TI  - Assessing the risk of pH-dependent absorption for new molecular entities: a novel
      in vitro dissolution test, physicochemical analysis, and risk assessment
      strategy.
AB  - Weak base therapeutic agents can show reduced absorption or large pharmacokinetic
      variability when coadministered with pH-modifying agents, or in achlorhydria
      disease states, due to reduced dissolution rate and/or solubility at high gastric
      pH. This is often referred to as pH-effect. The goal of this study was to
      understand why some drugs exhibit a stronger pH-effect than others. To study
      this, an API-sparing, two-stage, in vitro microdissolution test was developed to
      generate drug dissolution, supersaturation, and precipitation kinetic data under
      conditions that mimic the dynamic pH changes in the gastrointestinal tract. In
      vitro dissolution was assessed for a chemically diverse set of compounds under
      high pH and low pH, analogous to elevated and normal gastric pH conditions
      observed in pH-modifier cotreated and untreated subjects, respectively.
      Represented as a ratio between the conditions, the in vitro pH-effect correlated
      linearly with clinical pH-effect based on the Cmax ratio and in a non-linear
      relationship based on AUC ratio. Additionally, several in silico approaches that
      use the in vitro dissolution data were found to be reasonably predictive of the
      clinical pH-effect. To explore the hypothesis that physicochemical properties are
      predictors of clinical pH-effect, statistical correlation analyses were conducted
      using linear sequential feature selection and partial least-squares regression.
      Physicochemical parameters did not show statistically significant linear
      correlations to clinical pH-effect for this data set, which highlights the
      complexity and poorly understood nature of the interplay between parameters.
      Finally, a strategy is proposed for implementation early in clinical development,
      to systematically assess the risk of clinical pH-effect for new molecular
      entities that integrates physicochemical analysis and in vitro, in vivo and in
      silico methods. 

PMID- 24032350
TI  - TTE for fluid responsiveness?

PMID- 24032351
TI  - 2,3-cis-procyanidins elicit endothelium-dependent relaxation in porcine coronary
      arteries via activation of the PI3/Akt kinase signaling pathway.
AB  - Polyphenols including procyanidins have been reported to reduce the risk of
      cardiovascular diseases. However, polyphenolic extracts represent complex
      mixtures, and detailed information on their chemical composition is commonly
      lacking. The aim of this study was to investigate the potential of a highly
      purified and chemically defined 2,3-cis-procyanidin sample (di- to hexameric
      [4beta,8]-linked oligomers) from Nelia meyeri to relax coronary arteries and to
      get insight into the underlying mechanisms. The procyanidins produced a
      concentration-dependent relaxation in endothelium-intact vascular rings by
      activation of the NO and endothelium-derived hyperpolarizing factor (EDHF)
      signaling pathway via PI3/Akt kinase in a redox-sensitive manner, with O2(-) as
      key species predominantly produced by xanthine oxidase and NADPH oxidase. Our
      observations in tissue bath studies were confirmed by Western blotting; 2,3-cis
      procyanidins induced phosphorylation of eNOS and Akt in a ROS-dependent manner.
      These findings provide a basis for comparing the relaxant response and mode of
      action with that of structurally related proanthocyanidins. Our results may
      contribute to a better understanding of the potential link between the beneficial
      effects of proanthocyanidins on vascular health and their broad distribution in
      many fruits, natural food sources, and foodstuffs. 

PMID- 24032353
TI  - Robust automated mass spectra interpretation and chemical formula calculation
      using mixed integer linear programming.
AB  - Untargeted metabolite profiling using liquid chromatography and mass spectrometry
      coupled via electrospray ionization is a powerful tool for the discovery of novel
      natural products, metabolic capabilities, and biomarkers. However, the
      elucidation of the identities of uncharacterized metabolites from spectral
      features remains challenging. A critical step in the metabolite identification
      workflow is the assignment of redundant spectral features (adducts, fragments,
      multimers) and calculation of the underlying chemical formula. Inspection of the
      data by experts using computational tools solving partial problems (e.g.,
      chemical formula calculation for individual ions) can be performed to
      disambiguate alternative solutions and provide reliable results. However, manual
      curation is tedious and not readily scalable or standardized. Here we describe an
      automated procedure for the robust automated mass spectra interpretation and
      chemical formula calculation using mixed integer linear programming optimization
      (RAMSI). Chemical rules among related ions are expressed as linear constraints
      and both the spectra interpretation and chemical formula calculation are
      performed in a single optimization step. This approach is unbiased in that it
      does not require predefined sets of neutral losses and positive and negative
      polarity spectra can be combined in a single optimization. The procedure was
      evaluated with 30 experimental mass spectra and was found to effectively identify
      the protonated or deprotonated molecule ([M + H](+) or [M - H](-)) while being
      robust to the presence of background ions. RAMSI provides a much-needed
      standardized tool for interpreting ions for subsequent identification in
      untargeted metabolomics workflows. 

PMID- 24032352
TI  - A geochemical approach to determine sources and movement of saline groundwater in
      a coastal aquifer.
AB  - Geochemical evaluation of the sources and movement of saline groundwater in
      coastal aquifers can aid in the initial mapping of the subsurface when geological
      information is unavailable. Chloride concentrations of groundwater in a coastal
      aquifer near San Diego, California, range from about 57 to 39,400 mg/L. On the
      basis of relative proportions of major-ions, the chemical composition is
      classified as Na-Ca-Cl-SO4, Na-Cl, or Na-Ca-Cl type water. delta(2)H and
      delta(18)O values range from -47.70/00 to -12.80/00 and from -7.00/00 to 
      1.20/00, respectively. The isotopically depleted groundwater occurs in the deeper
      part of the coastal aquifer, and the isotopically enriched groundwater occurs in
      zones of sea water intrusion. (87)Sr/(86)Sr ratios range from about 0.7050 to
      0.7090, and differ between shallower and deeper flow paths in the coastal
      aquifer. (3)H and (14)C analyses indicate that most of the groundwater was
      recharged many thousands of years ago. The analysis of multiple chemical and
      isotopic tracers indicates that the sources and movement of saline groundwater in
      the San Diego coastal aquifer are dominated by: (1) recharge of local
      precipitation in relatively shallow parts of the flow system; (2) regional flow
      of recharge of higher-elevation precipitation along deep flow paths that freshen
      a previously saline aquifer; and (3) intrusion of sea water that entered the
      aquifer primarily during premodern times. Two northwest-to-southeast trending
      sections show the spatial distribution of the different geochemical groups and
      suggest the subsurface in the coastal aquifer can be separated into two
      predominant hydrostratigraphic layers.

PMID- 24032354
TI  - Pancake syndrome induced by ingestion of tempura.

PMID- 24032356
TI  - Dissolution properties, solid-state transformation and polymorphic
      crystallization: progesterone case study.
AB  - Progesterone is a natural steroid hormone and a poor soluble drug which presents
      two polymorphs (forms 1 and 2). Different methods to obtain form 2 were tested
      and a complete solid-state characterization of both polymorphs (forms 1 and 2)
      was conducted. X-ray powder diffraction, hot stage microscopy, Fourier transform
      infrared, dispersive Raman, (13)C solid-state nuclear magnetic resonance
      spectroscopy, thermal analysis, scanning electron microscopy techniques and
      intrinsic dissolution rates (IDR) were applied to investigate physical-chemical
      and dissolution properties of these two polymorphs. Form 2 was obtained from
      diluted solutions and from melting after cooling at room temperature. Form 1 was
      obtained from concentrated solutions and, a mixture of both polymorphs was
      crystallized from intermediate solutions. The crystal habit was not a distinctive
      characteristic of each polymorph. The effect of mechanical stress was evaluated
      in the metastable polymorph (form 2). We observed that grinding form 2 produced
      seeds of form 1 that induced the transformation of form 2 into form 1 at high
      temperature. The polymorphic quantification from XRD patterns of ground samples
      were carried out by the Rietveld method. After grinding and at room temperature
      conditions (~25  degrees C), it was observed the transformation of 17% of form 2
      into form 1 in 10 days.

PMID- 24032357
TI  - School absence due to toothache associated with sociodemographic factors, dental
      caries status, and oral health-related quality of life in 12- and 15-year-old
      Thai children.
AB  - OBJECTIVES: The objective of this study is to assess prevalence and extent of
      school absence due to toothache, dental caries, and Oral Health-Related Quality
      of Life (OHRQoL) in a subsample of the Thailand national oral health survey. In
      addition, associations of school absence as the outcome variable with explanatory
      behavioral and sociodemographic variables, dental caries, and OHRQoL were
      investigated. METHODS: Study sample was half of the Sixth Thailand National Oral
      Health Survey sample (1,063 12-year-old and 811 15-year-old children). Children
      were orally examined and interviewed about OHRQoL using the Child Oral Impacts on
      Daily Performances or the Oral Impacts on Daily Performances indices. Children
      completed a sociodemographic and behavioral questionnaire on school absence due
      to toothache in current semester. RESULTS: Over a 3-month period, 5.1 percent of
      12- and 4.4 percent of 15-year-olds absented themselves from school due to
      toothache. The number of days absent in 12-year-olds was significantly higher
      than in 15-year-olds. For 12-year-olds, OHRQoL and toothache were significantly
      associated with school absence. Severe dental decay was the main dental factor
      related to school absence but not significantly associated with school absence in
      the adjusted analyses. Children in lower school grades and those who received
      dental treatment in current semester were more likely to miss school compared
      with their counterparts. CONCLUSIONS: About one in 20 of Thai school-aged
      children reported missing school due to toothache. School absence due to
      toothache was inversely associated with the current year of study and positively
      with recently receiving dental treatment and with OHRQoL and toothache in 12-year
      olds.

PMID- 24032355
TI  - Neuron-specific specificity protein 4 bigenomically regulates the transcription
      of all mitochondria- and nucleus-encoded cytochrome c oxidase subunit genes in
      neurons.
AB  - Neurons are highly dependent on oxidative metabolism for their energy supply, and
      cytochrome c oxidase (COX) is a key energy-generating enzyme in the mitochondria.
      A unique feature of COX is that it is one of only four proteins in mammalian
      cells that are bigenomically regulated. Of its thirteen subunits, three are
      encoded in the mitochondrial genome and ten are nuclear-encoded on nine different
      chromosomes. The mechanism of regulating this multisubunit, bigenomic enzyme
      poses a distinct challenge. In recent years, we found that nuclear respiratory
      factors 1 and 2 (NRF-1 and NRF-2) mediate such bigenomic coordination. The latest
      candidate is the specificity factor (Sp) family of proteins. In N2a cells, we
      found that Sp1 regulates all 13 COX subunits. However, we discovered recently
      that in primary neurons, it is Sp4 and not Sp1 that regulates some of the key
      glutamatergic receptor subunit genes. The question naturally arises as to the
      role of Sp4 in regulating COX in primary neurons. The present study utilized
      multiple approaches, including chromatin immunoprecipitation, promoter mutational
      analysis, knockdown and over-expression of Sp4, as well as functional assays to
      document that Sp4 indeed functionally regulate all 13 subunits of COX as well as
      mitochondrial transcription factors A and B. The present study discovered that
      among the specificity family of transcription factors, it is the less known
      neuron-specific Sp4 that regulates the expression of all 13 subunits of
      mitochondrial cytochrome c oxidase (COX) enzyme in primary neurons. Sp4 also
      regulates the three mitochondrial transcription factors (TFAM, TFB1M, and TFB2M)
      and a COX assembly protein SURF-1 in primary neurons. 

PMID- 24032358
TI  - Abstracts of the European Academy of Childhood Disability 25th Annual Meeting.
      October 1-12, 2013. Newcastle-Gateshead, United Kingdom.

PMID- 24032359
TI  - Evaluating and approaching a strange animal: children's trust in informant
      testimony.
AB  - This study examined 3- to 7-year-old children's reliance on informant testimony
      to learn about a novel animal. Sixty participants were given positive or negative
      information about an Australian marsupial from an informant described as a
      maternal figure or a zookeeper. Children were asked which informant was correct
      and were invited to touch the animal, which was a stuffed toy hidden in a crate.
      Overall, younger children endorsed the zookeeper's testimony about the animal,
      but touched the animal more readily when the maternal figure provided positive
      information. Older children endorsed the informant who provided positive
      information, but showed some sensitivity to zookeeper expertise. Age differences
      were obtained in the association between participant characteristics and
      informant selection and animal approach behavior. 

PMID- 24032360
TI  - Growth and molecular responses to long-distance stimuli in poplars: bending vs
      flame wounding.
AB  - Inter-organ communication is essential for plants to coordinate development and
      acclimate to mechanical environmental fluctuations. The aim of this study was to
      investigate long-distance signaling in trees. We compared on young poplars the
      short-term effects of local flame wounding and of local stem bending for two
      distal responses: (1) stem primary growth and (2) the expression of
      mechanoresponsive genes in stem apices. We developed a non-contact measurement
      method based on the analysis of apex images in order to measure the primary
      growth of poplars. The results showed a phased stem elongation with alternating
      nocturnal circumnutation phases and diurnal growth arrest phases in Populus
      tremula * alba clone INRA 717-1B4. We applied real-time polymerase chain reaction
      (RT-PCR) amplifications in order to evaluate the PtaZFP2, PtaTCH2, PtaTCH4,
      PtaACS6 and PtaJAZ5 expressions. The flame wounding inhibited primary growth and
      triggered remote molecular responses. Flame wounding induced significant changes
      in stem elongation phases, coupled with inhibition of circumnutation. However,
      the circadian rhythm of phases remained unaltered and the treated plants were
      always phased with control plants during the days following the stress. For bent
      plants, the stimulated region of the stem showed an increased PtaJAZ5 expression,
      suggesting the jasmonates may be involved in local responses to bending. No
      significant remote responses to bending were observed.

PMID- 24032361
TI  - Histopathological changes in rabbit gastric mucosa after chronic exposure to
      pickled vegetables: an experimental study.
AB  - Gastric cancer (GC) is very common in Iran. Daily consumption of pickled
      vegetables is a routine dietary habit in most areas of Iran. Because pickled
      vegetables have been associated with GC it can be of importance to study the
      relationship between the two. We have therefore studied the histo-morphological
      effects of pickled vegetables on the Rabbit gastric mucosa. Forty and twenty
      healthy male rabbits were respectively allocated in the experimental and control
      groups. The rabbits were fed freely with pickled (experimental group) and fresh
      vegetables (control group) for 1 yr. The gastric mucosa of rabbits was examined
      and the results were compared. In addition to all the rabbits of the control
      group, 14 rabbits (35%) of the experimental group had normal gastric mucosa. The
      rest showed abnormal changes including atypia-so called indefinite for dysplasia
      in 10 (25%), low-grade dysplasia in 14 (35%), and high-grade dysplasia in 2 (5%).
      The analysis showed significant difference between results of the 2 groups (P <
      0.001). Daily consumption of pickled vegetables can produce atypical and
      dysplastic changes in the gastric mucosa. Such preneoplastic changes can
      potentially transform to gastric carcinoma. This process could be prevented by
      reduction or cessation of daily pickled food consumption. 

PMID- 24032362
TI  - Evaluating and adapting the Mediterranean diet for non-Mediterranean populations:
      a critical appraisal.
AB  - This review outlines the limitations of current techniques for evaluating the
      Mediterranean diet in Mediterranean versus non-Mediterranean populations.
      Differences between the two populations with regard to the foods that are
      available, food processing and preparation techniques, and eating and lifestyle
      habits may influence the implementation and effects of a Mediterranean diet in
      non-Mediterranean regions. For example, the composition of food groups may vary
      significantly, due to differences in the specific foods within a food group and
      to differences in aspects of food production and preparation. Notable differences
      between the diets of Mediterranean versus non-Mediterranean populations include
      the source of monounsaturated fatty acids (olive oil versus meat), the amount of
      vegetables consumed and their manner of preparation, the source of alcohol (wine
      versus other) and the pattern of intake, and the types of meat and dairy products
      consumed. Lifestyle factors such as meal patterns and exposure to sunlight may
      also act as confounding factors when the overall benefits of a Mediterranean diet
      are assessed. Improving the calculation of Mediterranean diet scores and
      measuring plasma nutrient levels may help mitigate the effects of confounders.
      These considerations could have important health implications when a
      Mediterranean diet is implemented by non-Mediterranean populations. 

PMID- 24032364
TI  - Fatty acid consumption and the risk of osteoporotic fracture.
AB  - Osteoporosis is a disease characterized by low bone mass and the structural
      deterioration of bone tissue. It is estimated that 44 million Americans and 55%
      of those over 50 years of age are currently affected by this disease. Among other
      risk factors for osteoporotic fracture, dietary fat in general and essential
      fatty acids (EFA) in particular have recently been investigated because of their
      suspected impact on the bone remodeling process. This article reviews the growing
      body of literature concerning EFA and bone health. In particular, two recent
      large prospective cohort studies evaluating the association between multiple
      types of EFA and risk of osteoporotic fracture are highlighted. The results of
      these studies are placed in context with the existing literature, and
      recommendations for future investigation are presented. 

PMID- 24032363
TI  - Dietary phytochemicals in cancer prevention and therapy: a complementary approach
      with promising perspectives.
AB  - The population is aging. Over the coming years, the incidence of age-related
      chronic diseases such as cancer is expected to continue to increase.
      Phytochemicals, which are non-nutritive chemicals found in plants and food, have
      emerged as modulators of key cellular signaling pathways exerting proven
      anticancer effects. The challenge now is to develop personalized supplements
      comprised of specific phytochemicals for each clinical situation. This will be
      possible once a better understanding is gained of the molecular basis explaining
      the impact of phytochemicals on human health. The aim of the present literature
      review is to summarize current knowledge of the dietary phytochemicals with
      proven antitumor activity, with a special emphasis placed on their molecular
      targets. Also discussed are the limits of existing research strategies and the
      future directions of this field. 

PMID- 24032365
TI  - Clinical outcomes of vitamin D deficiency and supplementation in cancer patients.
AB  - Results of recent studies suggest that circulating levels of vitamin D may play
      an important role in cancer-specific outcomes. The present systematic review was
      undertaken to determine the prevalence of vitamin D deficiency (<25 nmol/L) and
      insufficiency (25-50 nmol/L) in cancer patients and to evaluate the association
      between circulating calcidiol (the indicator of vitamin D status) and clinical
      outcomes. A systematic search of original, peer-reviewed studies on calcidiol at
      cancer diagnosis, and throughout treatment and survival, was conducted yielding
      4,706 studies. A total of 37 studies met the inclusion criteria for this review.
      Reported mean blood calcidiol levels ranged from 24.7 to 87.4 nmol/L, with up to
      31% of patients identified as deficient and 67% as insufficient. The efficacy of
      cholecalciferol supplementation for raising the concentration of circulating
      calcidiol is unclear; standard supplement regimens of <1,000 IU D3 /day may not
      be sufficient to maintain adequate concentrations or prevent decreasing
      calcidiol. Dose-response studies linking vitamin D status to musculoskeletal and
      survival outcomes in cancer patients are lacking.

PMID- 24032366
TI  - Aligning nutrition assistance programs with the Dietary Guidelines for Americans.
AB  - Nutrition assistance programs, including the Special Supplemental Nutrition
      Program for Women, Infants, and Children (WIC), the National School Lunch and
      School Breakfast Programs (NSLP/SBP), and the Child and Adult Care Food Program
      (CACFP), are intended to offer low-income families the opportunity for a
      healthier food pattern that promotes overall health and reduces risk for chronic
      disease. To be successful in improving the diets of underserved Americans
      requires a unified approach toward meeting the nutritional needs of program
      participants. Newly revised recommendations increase intakes of fruits,
      vegetables, and whole-grain-rich foods while reducing consumption of saturated
      fats, added sugars, and sodium. In addition to improving the nutritional profile
      of meals and snacks for NSLP and CACFP and meal patterns for WIC, the new
      recommendations ensure variety within food groups for menus across a week and
      allow for regional and cultural preferences and increased flexibility of choice
      within food groups. The newly revised meal pattern recommendations are broadly
      applicable to the design of feeding programs for any age group and for any
      combination of meals and snacks being provided. 

PMID- 24032367
TI  - Role of dietary factors in survival and mortality in colorectal cancer: a
      systematic review.
AB  - The role of dietary factors in the outcome of colorectal cancer (CRC) has been
      the subject of many studies, but results are inconclusive. Presented here are the
      results of a systematic review of studies published on dietary factors and CRC
      outcome in the English literature between March 2002 and March 2012. Studies were
      subdivided into survival studies in CRC patients and CRC mortality studies in the
      general population. Sixteen of the 636 studies identified--5 on survival and 11
      on mortality--met the predefined inclusion criteria. No consistent association
      between individual dietary components and CRC outcome was detected in the
      survival studies. In the mortality studies, an association between meat intake
      and increased CRC mortality was found in two ecologic studies; however, two
      prospective cohort studies did not confirm this association. An inverse
      association between cereal intake and CRC mortality was found in two ecologic
      studies. In conclusion, published studies investigating dietary factors and
      outcome in CRC are heterogeneous in design and findings. No dietary component was
      conclusively and consistently associated with survival in CRC patients. The
      results of mortality studies seem to indicate that meat intake has an adverse
      effect on CRC mortality, while cereal intake may be protective.

PMID- 24032368
TI  - Experimental and theoretical characterization of the 2(2)A'-1(2)A' transition of
      BeOH/D.
AB  - The hydroxides of Ca, Sr, and Ba are known to be linear molecules, while MgOH is
      quasilinear. High-level ab initio calculations for BeOH predict a bent
      equilibrium structure with a bond angle of 140.9 degrees , indicating a
      significant contribution of covalency to the bonding. However, experimental
      confirmation of the bent structure is lacking. In the present study, we have used
      laser excitation techniques to observe the 2(2)A'-1(2)A' transition of BeOH/D in
      the energy range of 30300-32800 cm(-1). Rotationally resolved spectra were
      obtained, with sufficient resolution to reveal spin splittings for the
      electronically excited state. Two-color photoionization was used to determine an
      ionization energy of 66425(10) cm(-1). Ab initio calculations were used to guide
      the analysis of the spectroscopic data. Multireference configuration interaction
      calculations were used to construct potential energy surfaces for the 1(2)A',
      2(2)A', and 1(2)A" states. The rovibronic eigenstates supported by these surfaces
      were determined using the Morse oscillator rigid bender internal dynamics
      Hamiltonian. The theoretical results were in sufficiently good agreement with the
      experimental data to permit unambiguous assignment. It was confirmed that the
      equilibrium geometry of the ground state is bent and that the barrier to
      linearity lies below the zero-point energies for both BeOH and BeOD.

PMID- 24032369
TI  - A computational study of the copper(II)-catalyzed enantioselective intramolecular
      aminooxygenation of alkenes.
AB  - The origin of the enantioselectivity in the [Cu(R,R)-Ph-box](OTf)2-catalyzed
      intramolecular aminooxygenation of N-sulfonyl-2-allylanilines and 4
      pentenylsulfonamides to afford chiral indolines and pyrrolidines, respectively,
      was investigated using density functional theory (DFT) calculations. The
      pyrrolidine-forming transition-state model for the major enantiomer involves a
      chairlike seven-membered cyclization transition state with a distorted square
      planar copper center, while the transition-state model for the minor enantiomer
      was found to have a boatlike cyclization geometry having a distorted tetrahedral
      geometry about the copper center. Similar copper-geometry trends were observed in
      the chiral indoline-forming reactions. These models were found to be
      qualitatively consistent with experimental results and allow for rationalization
      of how substitution on the substrate backbone and N-sulfonyl substituent affect
      the level of enantioselectivity in these and related copper(II)-catalyzed
      enantioselective reactions. 

PMID- 24032370
TI  - Prostate histoscanning in clinically localized biopsy proven prostate cancer: an
      accuracy study.
AB  - PURPOSE: To assess the accuracy of prostate histoscanning (PHS) for spatial
      detection and localization of prostate cancer (PCa). PATIENTS AND METHODS:
      Prospective, single center study from January to September 2012 was conducted.
      Inclusion criterion was biopsy confirmed PCa in patients scheduled for radical
      prostatectomy. In total, 98 patients were included in the study. Results of PHS
      were compared against whole-mount step sectioning by the Stanford technique. A
      lower limit of 0.1 cm(3) was used for PHS. A dedicated 12-sector form was used
      for spatial correlation. The urologist and pathologist were blinded for each
      other's results. Sensitivity, specificity, and receiver operating characteristic
      curves were calculated with a logistic regression model for covariates. RESULTS:
      PHS performance for detection of PCa lesions >=0.1 cm(3) had sensitivity of 60%,
      specificity of 66%, and area under the curve (AUC) of 0.63. Posterior and
      anterior sectors achieved sensitivity of 77%, specificity of 39%, and 28% and
      84%, respectively. The model containing PHS positivity within a given sector
      reached sensitivity of 73.4%, specificity of 65.7%, and AUC of 0.75. In a ogistic
      regression model, the performance of PHS was affected by sector location, rectal
      distance, index, and total cancer volume (all P<0.0001) and bladder fullness
      (P=0.02). The best PHS accuracy was present in midposterior sectors. CONCLUSIONS:
      PHS has a potential for clinical practice, especially if PHS positivity within
      given sectors is taken into account. A trained operator is important. More
      studies are necessary to test different detection limits in various clinical
      settings, such as targeted biopsies and image guided focal therapy.

PMID- 24032371
TI  - Au10Mo4Zn89: a fully ordered complex intermetallic compound analyzed by TOPOS.
AB  - The compound Au10Mo4Zn89 has been synthesized, and its structure has been
      analyzed by single-crystal X-ray diffraction. The compound crystallizes in cubic
      space group F43m (No. 216) with a unit cell that contains 412 atoms. The
      structure is largely tetrahedrally closely packed, but an octahedral arrangement
      of atoms is incompatible with tetrahedral close packing. The structure of the
      ordered Au10Mo4Zn89 compound has been described by using the algorithm of
      automatic geometric and topological analysis that is implemented in TOPOS as the
      "Nanoclustering" procedure.

PMID- 24032372
TI  - Influence of seasonal variation and methyl jasmonate mediated induction of
      glucosinolate biosynthesis on quinone reductase activity in broccoli florets.
AB  - Methyl jasmonate spray treatments (250 MUM) were utilized to alter glucosinolate
      composition in the florets of the commercial broccoli F1 hybrids 'Pirate',
      'Expo', 'Green Magic', 'Imperial', and 'Gypsy' grown in replicated field
      plantings in 2009 and 2010. MeJA treatment significantly increased glucoraphanin
      (11%), gluconasturtiin (59%), and neoglucobrassicin (248%) concentrations and
      their hydrolysis products including sulforaphane (152%), phenethyl isothiocyanate
      (318%), N-methoxyindole-3-carbinol (313%), and neoascorbigen (232%) extracted
      from florets of these genotypes over two seasons. Increased quinone reductase
      (QR) activity was significantly correlated with increased levels of sulforaphane,
      N-methoxyindole-3-carbinol, and neoascorbigen. Partitioning experiment-wide trait
      variances indicated that the variability in concentrations of sulforaphane (29%),
      neoascorbigen (48%), and QR activity (72%) was influenced by year-associated
      weather variables, whereas variation in neoglucobrassicin (63%) and N
      methoxyindole-3-carbinol (46%) concentrations was primarily attributed to methyl
      jasmonate treatment. These results suggest that methyl jasmonate treatment can
      enhance QR inducing activity by increased hydrolysis of glucoraphanin into
      sulforaphane and the hydrolysis products of neoglucobrassicin. 

PMID- 24032373
TI  - Design and characterization of chitosan-alginate microspheres for ocular delivery
      of azelastine.
AB  - The use of mucoadhesive biopolymers is one of the best approaches to prolong the
      drug residence inside the cul-de-sac, consequently increasing the
      bioavailability. Thus, the focus of this work was to develop mucoadhesive
      microspheres to overcome the limitations of ocular drug delivery. The chitosan
      sodium alginate microspheres of azelastine hydrochloride were fabricated using
      modified ionotropic gelation technique. The particle size, zeta potential,
      entrapment efficiency and drug release kinetics were evaluated and characterized
      by SEM, FT-IR, DSC, in vitro mucoadhesion and in vivo study. The microspheres had
      average particle size in the range of 3.55 to 6.70 um and zeta potential +24.55
      to +49.56 mV. The fabricated microspheres possess maximum drug entrapment of
      73.05% with 65% mucin binding efficiency and revealed a controlled release over
      the 8-h period following a non-Fickian diffusion. SEM showed that microspheres
      were distinct solid with irregular shape. FT-IR and DSC results concluded the
      drug entrapment into microspheres. In vivo studies on ocular rat model revealed
      that azelastine microspheres had better efficacy. Chitosan sodium alginate
      microspheres prepared were in particle size range suitable for ocular purpose. In
      vitro release and in vivo efficacy studies revealed that the microspheres were
      effective in prolonging the drug's presence in cul de sac with improved
      therapeutic efficacy.

PMID- 24032374
TI  - Surface-initiated dehydrogenative polymerization of monolignols: a quartz crystal
      microbalance with dissipation monitoring and atomic force microscopy study.
AB  - This work highlights a real-time and label-free method to monitor the
      dehydrogenative polymerization of monolignols initiated by horseradish peroxidase
      (HRP) physically immobilized on surfaces using a quartz crystal microbalance with
      dissipation monitoring (QCM-D). The dehydrogenative polymer (DHP) films are
      expected to provide good model substrates for studying ligninolytic enzymes. The
      HRP was adsorbed onto gold or silica surfaces or onto and within porous
      desulfated nanocrystalline cellulose films from an aqueous solution. Surface
      immobilized HRP retained its activity and selectivity for monolignols as
      coniferyl and p-coumaryl alcohol underwent dehydrogenative polymerization in the
      presence of hydrogen peroxide, whereas sinapyl alcohol polymerization required
      the addition of a nucleophile. The morphologies of the DHP layers on the surfaces
      were investigated via atomic force microscopy (AFM). Data from QCM-D and AFM
      showed that the surface-immobilized HRP-initiated dehydrogenative polymerization
      of monolignols was greatly affected by the support surface, monolignol
      concentration, hydrogen peroxide concentration, and temperature. 

PMID- 24032375
TI  - Tryptophan-accelerated electron flow across a protein-protein interface.
AB  - We report a new metallolabeled blue copper protein, Re126W122Cu(I) Pseudomonas
      aeruginosa azurin, which has three redox sites at well-defined distances in the
      protein fold: Re(I)(CO)3(4,7-dimethyl-1,10-phenanthroline) covalently bound at
      H126, a Cu center, and an indole side chain W122 situated between the Re and Cu
      sites (Re-W122(indole) = 13.1 A, dmp-W122(indole) = 10.0 A, Re-Cu = 25.6 A). Near
      UV excitation of the Re chromophore leads to prompt Cu(I) oxidation (<50 ns),
      followed by slow back ET to regenerate Cu(I) and ground-state Re(I) with
      biexponential kinetics, 220 ns and 6 MUs. From spectroscopic measurements of
      kinetics and relative ET yields at different concentrations, it is likely that
      the photoinduced ET reactions occur in protein dimers, (Re126W122Cu(I))2 and that
      the forward ET is accelerated by intermolecular electron hopping through the
      interfacial tryptophan: *Re//<-W122<-Cu(I), where // denotes a protein-protein
      interface. Solution mass spectrometry confirms a broad oligomer distribution with
      prevalent monomers and dimers, and the crystal structure of the Cu(II) form shows
      two Re126W122Cu(II) molecules oriented such that redox cofactors Re(dmp) and W122
      indole on different protein molecules are located at the interface at much
      shorter intermolecular distances (Re-W122(indole) = 6.9 A, dmp-W122(indole) = 3.5
      A, and Re-Cu = 14.0 A) than within single protein folds. Whereas forward ET is
      accelerated by hopping through W122, BET is retarded by a space jump at the
      interface that lacks specific interactions or water molecules. These findings on
      interfacial electron hopping in (Re126W122Cu(I))2 shed new light on optimal redox
      unit placements required for functional long-range charge separation in protein
      complexes. 

PMID- 24032376
TI  - Quercetin increases the efficacy of glioblastoma treatment compared to standard
      chemoradiotherapy by the suppression of PI-3-kinase-Akt pathway.
AB  - The goal of the present study was to compare the efficacy of treatment with
      irradiation (IR), temozolomide, and quercetin, alone, or in combinations, on 2
      glioblastoma cell lines, DBTRG-05 and U-251. Cell viability assay, flow cytometry
      analysis, colony formation assay, and Western blot analysis were used to compare
      the effects of treatment on the 2 cell lines. The greatest reduction in cell
      viability and colony formation was observed when cells were treated with a
      combination of the agents including quercetin. The treatment of cells with the
      combination of IR and quercetin was equal to the efficiency of the combination of
      IR and temozolomide in decreasing cell viability as well as colony formation.
      Quercetin alone, or in combination with IR, increased the cleavage of caspase-3
      and PARP-1 showing an activated apoptosis and significantly reduced the level of
      phospho-Akt. Moreover, these treatments increased the levels of phospho-ERK,
      phospho-JNK, phospho-p38, and phospho-RAF1. Our data indicate that the
      supplementation of standard therapy with quercetin increases efficacy of
      treatment of experimental glioblastoma through synergism in the induction of
      apoptosis via the cleavage of caspase-3 and PARP-1 and by the suppression of the
      actitivation of Akt pathway. 

PMID- 24032377
TI  - Healthcare disparities in patients with acute respiratory distress syndrome.
      Toward equity.

PMID- 24032378
TI  - Type 2 immune responses in obese individuals with asthma.

PMID- 24032379
TI  - Faster, higher, stronger.

PMID- 24032380
TI  - Alveolar macrophage dysfunction and chronic alcohol use. Time to think about
      zinc.

PMID- 24032381
TI  - Envisioning sophisticated electronic health records through the lens of health
      care reform.

PMID- 24032383
TI  - Angiosarcoma with extensive pulmonary metastases, presenting with spontaneous
      bilateral pneumothoraces.

PMID- 24032384
TI  - Concepts of arterial oxygen saturation in the presence of carboxyhemoglobin.

PMID- 24032385
TI  - Reply: Concepts of arterial oxygen saturation in the presence of
      carboxyhemoglobin.

PMID- 24032386
TI  - The effect of etanercept on lung leukocyte margination and fibrin deposition
      after cardiac surgery.

PMID- 24032382
TI  - An official American Thoracic Society/European Respiratory Society statement:
      Update of the international multidisciplinary classification of the idiopathic
      interstitial pneumonias.
AB  - BACKGROUND: In 2002 the American Thoracic Society/European Respiratory Society
      (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs) defined
      seven specific entities, and provided standardized terminology and diagnostic
      criteria. In addition, the historical "gold standard" of histologic diagnosis was
      replaced by a multidisciplinary approach. Since 2002 many publications have
      provided new information about IIPs. PURPOSE: The objective of this statement is
      to update the 2002 ATS/ERS classification of IIPs. METHODS: An international
      multidisciplinary panel was formed and developed key questions that were
      addressed through a review of the literature published between 2000 and 2011.
      RESULTS: Substantial progress has been made in IIPs since the previous
      classification. Nonspecific interstitial pneumonia is now better defined.
      Respiratory bronchiolitis-interstitial lung disease is now commonly diagnosed
      without surgical biopsy. The clinical course of idiopathic pulmonary fibrosis and
      nonspecific interstitial pneumonia is recognized to be heterogeneous. Acute
      exacerbation of IIPs is now well defined. A substantial percentage of patients
      with IIP are difficult to classify, often due to mixed patterns of lung injury. A
      classification based on observed disease behavior is proposed for patients who
      are difficult to classify or for entities with heterogeneity in clinical course.
      A group of rare entities, including pleuroparenchymal fibroelastosis and rare
      histologic patterns, is introduced. The rapidly evolving field of molecular
      markers is reviewed with the intent of promoting additional investigations that
      may help in determining diagnosis, and potentially prognosis and treatment.
      CONCLUSIONS: This update is a supplement to the previous 2002 IIP classification
      document. It outlines advances in the past decade and potential areas for future
      investigation.

PMID- 24032387
TI  - The role of arrhythmias in defining cardiac dysfunction during sepsis.

PMID- 24032388
TI  - Reply: The role of arrhythmias in defining cardiac dysfunction during sepsis.

PMID- 24032389
TI  - Changes in physician reimbursement by medicare for critical care services from
      1998 to 2008.

PMID- 24032390
TI  - A proof of concept for the detection and classification of pulmonary arterial
      hypertension through breath analysis with a sensor array.

PMID- 24032391
TI  - Nasal neurogenic inflammation markers increase after diesel exhaust inhalation in
      individuals with asthma.

PMID- 24032392
TI  - Life-threatening bleeding after endobronchial biopsy in a patient with
      bronchiectasis.

PMID- 24032393
TI  - Role of central and peripheral chemoreceptors in vasopressin secretion control.
AB  - In this review, we analyzed the role played by central and peripheral
      chemoreceptors (CHRs) in vasopressin (AVP) secretion control. Central neural
      pathways subserving osmotic and non-osmotic control of AVP secretion are strictly
      correlated to brain areas participating in chemoreception mechanisms. Among the
      different brain areas involved in central chemoreception, the most important site
      has been localized in the retrotrapezoid nucleus of the rostral ventrolateral
      medulla. These central CHRs are able to detect very small pH/CO2 fluctuations,
      participating in brain blood flow regulation, acid-base balance and blood
      pressure control. Decreases in arterial pH and increases in arterial pCO2
      stimulate AVP release by the Supraoptic and Paraventricular Nuclei. Carotid CHRs
      transduce low arterial O2 tension into increased action potential activity,
      leading to bradycardia and coronary vasodilatation via vagal stimulation, and
      systemic vasoconstriction via catecholaminergic stimulation. Stimulation of
      carotid CHRs by hypoxia increases neurohypophyseal blood flow and AVP release, an
      effect inhibited by CHRs denervation. Two renal CHRs have been identified: Type
      R1 CHRs do not have a resting discharge but are activated by renal ischemia and
      hypotension; Type R2 CHRs have a resting discharge and respond to backflow of
      urine into the renal pelvis. Signals arising from renal CHRs modulate the
      activity of hypothalamic AVPergic neurons: activation of R1 and R2 CHRs,
      following increased intrapelvic pressure with solutions of mannitol, NaCl and
      KCl, produces a significant increase of AVP secretion and the same effect has
      been obtained by the intrarenal infusion of bradykinin, which excites afferent
      renal nerves, as well as by the electrical stimulation of these nerves. 

PMID- 24032395
TI  - Is universal screening for hepatitis C infection prior to commencing antitumour
      necrosis factor-alpha therapy necessary?
AB  - BACKGROUND: Screening for hepatitis C virus (HCV) prior to the commencement of
      antitumour necrosis factor (anti-TNF)-alpha therapies for dermatological disease
      is recommended for all patients. OBJECTIVES: To determine the incidence of HCV
      infection among dermatology patients who were screened for HCV infection prior to
      commencing anti-TNF-alpha therapies. METHODS: We reviewed the HCV infection
      status of all patients attending our dermatology department who had been tested
      for evidence of HCV infection between January 2005 and November 2012. We
      identified patients who had been tested as part of routine screening prior to
      commencing anti-TNF-alpha therapy using dermatology departmental records.
      RESULTS: In total, 215 patients were screened for HCV infection prior to
      commencing anti-TNF-alpha therapies. Among this group, 143 patients (66.5%) were
      male and 72 (33.5%) were female. None of these patients tested positive for
      active HCV infection. One patient tested positive for HCV antibody with negative
      HCV antigen and HCV RNA. This indicated previous HCV infection that had cleared.
      This patient had abnormal liver function tests and a history of alcohol excess.
      CONCLUSIONS: There were no cases of active HCV infection diagnosed through
      pretreatment anti-TNF-alpha screening in our department, which is located in a
      low-prevalence area for HCV infection. In view of the lack of evidence of harm
      associated with anti-TNF-alpha use in HCV-infected patients, we propose that
      screening for HCV infection in low-prevalence areas should be targeted to those
      with pre-existing risk factors. This is consistent with current guidelines from
      the Royal College of General Practitioners. Targeted screening rather than
      universal screening may be a safe and cost-effective option among patients being
      evaluated for anti-TNF-alpha therapies.

PMID- 24032394
TI  - Cerebral glucose metabolism in an immature rat model of pediatric traumatic brain
      injury.
AB  - Altered cerebral metabolism and mitochondrial function have been identified in
      experimental and clinical studies of pediatric traumatic brain injury (TBI).
      Metabolic changes detected using (1)H (proton) magnetic resonance spectroscopy
      correlate with long-term outcomes in children after severe TBI. We previously
      identified early (4-h) and sustained (24-h and 7-day) abnormalities in brain
      metabolites after controlled cortical impact (CCI) in immature rats. The current
      study aimed to identify specific alterations of cerebral glucose metabolism at 24
      h after TBI in immature rats. Rats (postnatal days 16-18) underwent CCI to the
      left parietal cortex. Sham rats underwent craniotomy only. Twenty-four hours
      after CCI, rats were injected (intraperitoneally) with [1,6-(13)C]glucose. Brains
      were removed, separated into hemispheres, and frozen. Metabolites were extracted
      with perchloric acid and analyzed using (1)H and (13)C-nuclear magnetic resonance
      spectroscopy. TBI resulted in decreases in N-acetylaspartate in both hemispheres,
      compared to sham contralateral. At 24 h after TBI, there was significant decrease
      in the incorporation of (13)C label into [3-(13)C]glutamate and [2
      (13)C]glutamate in the injured brain. There were no differences in percent
      enrichment of [3-(13)C]glutamate, [4-(13)C]glutamate, [3-(13)C]glutamine, or [4
      (13)C]glutamine. There was significantly lower percent enrichment of [2
      (13)C]glutamate in both TBI sides and the sham craniotomy side, compared to sham
      contralateral. No differences were detected in enrichment of (13)C glucose label
      in [2-(13)C]glutamine, [2-(13)C]GABA (gamma-aminobutyric acid), [3-(13)C]GABA, or
      [4-(13)C]GABA, [3-(13)C]lactate, or [3-(13)C]alanine between groups. Results
      suggest that overall oxidative glucose metabolism in the immature brain recovers
      at 24 h after TBI. Specific reductions in [2-(13)C]glutamate could be the result
      of impairments in either neuronal or astrocytic metabolism. Future studies should
      aim to identify pathways leading to decreased metabolism and develop cell
      selective "metabolic rescue."

PMID- 24032396
TI  - How does the cell overcome LCP nanoparticle-induced calcium toxicity?
AB  - To address the question of how cells respond to the possible Ca(2+) toxicity
      caused by the release of Ca(2+) into the cytoplasm by LCP nanoparticles, a series
      of in vitro and in vivo studies using Ca(2+) pump inhibitors were conducted. The
      results indicated that two major Ca(2+) pumps on the plasma membrane and the
      mitochondrial membrane, respectively, were able to rapidly respond to the
      elevated cytosolic Ca(2+) concentration and prevent Ca(2+)-induced apoptosis or
      necrosis. However, exposure to specific inhibitors of calcium pumps would cause
      LCP-treated H460 cells to undergo necrosis both in vitro and in vivo. These
      results demonstrated that the Ca(2+) delivered by LCP was not toxic to cells when
      the cells contain functional Ca(2+) pumps. 

PMID- 24032397
TI  - Cerebral hyperaemia after isoflurane anaesthesia for craniotomy of patients with
      supratentorial brain tumour.
AB  - BACKGROUND: Few studies look into cerebral blood flow (CBF) changes during
      emergence from general anaesthesia for craniotomy. The purpose of this study was
      to assess CBF changes during emergence from general anaesthesia for craniotomy,
      through monitoring blood oxygen saturation of jugular vein bulb (SjvO2 ) and
      transcranial Doppler (TCD). METHODS: We enrolled 30 patients undergoing selective
      craniotomy (group C) for supratentorial brain tumour resection and 30 patients
      undergoing selective abdominal surgery (group A). Mean velocity of middle
      cerebral artery (Vmca), mean arterial pressure (MAP), SjvO2 (only measured in
      group C), and arterial CO2 partial pressure were measured before anaesthesia, at
      tracheal extubation, and 30, 60, 90, 120 min after extubation. RESULTS: Vmca of
      the same side of tumour was significantly higher than contralateral Vmca before
      anaesthesia and at all times after extubation in group C. The ipsilateral Vmca
      increased significantly (95.7 +/- 16.9 cm/s vs. 63.7 +/- 6.7 cm/s, P < 0.01) at
      extubation in group C, then declined but still above baseline significantly in
      the first 2 h after extubation. While Vmca of the right side changed only
      slightly (63.6 +/- 7.7 cm/s vs. 61.8 +/- 8.1 cm/s, P < 0.01) but significantly at
      extubation in group A. SjvO2 increased significantly (81.4% +/- 7.4% vs. 60.9% +/
      3.7%, P < 0.01) at extubation in group C, and remained above baseline
      significantly for 2 h. There was no significant correlation between Vmca and MAP
      at any time. CONCLUSIONS: Cerebral hyperaemia occurs after supratentorial brain
      tumour resection surgery. The hyperaemia is more pronounced on the same side as
      the tumour.

PMID- 24032398
TI  - A silver cluster-DNA equilibrium.
AB  - DNA encapsulates silver clusters, and these hybrid nanomaterials form molecular
      sensors. We discuss a silver cluster-oligonucleotide sensor with four
      characteristics. First, a specific reporting cluster forms within a single
      stranded DNA. This template uses the 5' cluster domain CCCCAACTCCTT with
      different 3' recognition sites for complementary oligonucleotides. The modular
      composite strand exclusively forms a cluster with lambdamax = 400 nm and with low
      emission. Conjugates were chromatographically purified, and their elemental
      analysis measured a cluster adduct with ~11 silver atoms. Second, hybridization
      transforms the cluster. Size exclusion chromatography shows that the 3'
      recognition sites of the single-stranded conjugates hybridize with their
      complements. This secondary structural change both shifts cluster absorption from
      400 to 490 nm and develops emission at 550 nm. Third, cluster size remains
      intact. Like their violet predecessors, purified blue-green clusters have ~11
      silver atoms. Cluster integrity is further supported by extracting the complement
      from the blue-green conjugate and reversing the spectral changes. Fourth, the
      cluster transformation is an equilibrium. Complementary strands generate an
      isosbestic point and thus directly link single-stranded hosts for the violet
      cluster and their hybridized analogs for the blue-green cluster. This equilibrium
      shifts with temperature. A van't Hoff analysis shows that longer and more stable
      duplexes favor the blue-green cluster. However, hybridized cluster hosts are less
      stable than their native DNA counterparts, and stability further degrades when
      short complements expose nucleobases within S1-S2. Duplex instability suggests
      that unpaired nucleobases coordinate the violet cluster and favor the single
      stranded sensor. A balance between innate hybridization and exogenous folding
      highlights a distinct feature of silver clusters for sensing: they are both
      chromophoric reporters and ligands that modulate analyte-sensor interactions. 

PMID- 24032399
TI  - When can inverted water tables occur beneath streams?
AB  - Decline in regional water tables (RWT) can cause losing streams to disconnect
      from underlying aquifers. When this occurs, an inverted water table (IWT) will
      develop beneath the stream, and an unsaturated zone will be present between the
      IWT and the RWT. The IWT marks the base of the saturated zone beneath the stream.
      Although a few prior studies have suggested the likelihood of an IWT without a
      clogging layer, most of them have assumed that a low-permeability streambed is
      required to reduce infiltration from surface water to groundwater, and that the
      IWT only occurs at the bottom of the low-permeability layer. In this study, we
      use numerical simulations to show that the development of an IWT beneath an
      unclogged stream is theoretically possible under steady-state conditions. For a
      stream width of 1 m above a homogeneous and isotropic sand aquifer with a 47 m
      deep RWT (measured in an observation point 20 m away from the center of the
      stream), an IWT will occur provided that the stream depth is less than a critical
      value of 4.1 m. This critical stream depth is the maximum water depth in the
      stream to maintain the occurrence of an IWT. The critical stream depth decreases
      with stream width. For a stream width of 6 m, the critical stream depth is only 1
      mm. Thus while theoretically possible, an IWT is unlikely to occur at steady
      state without a clogging layer, unless a stream is very narrow or shallow and the
      RWT is very deep. 

PMID- 24032400
TI  - Periodontal regeneration using periodontal ligament stem cell-transferred amnion.
AB  - Periodontal disease is characterized by the destruction of tooth supporting
      tissues. Regeneration of periodontal tissues using ex vivo expanded cells has
      been introduced and studied, although appropriate methodology has not yet been
      established. We developed a novel cell transplant method for periodontal
      regeneration using periodontal ligament stem cell (PDLSC)-transferred amniotic
      membrane (PDLSC-amnion). The aim of this study was to investigate the
      regenerative potential of PDLSC-amnion in a rat periodontal defect model.
      Cultured PDLSCs were transferred onto amniotic membranes using a glass substrate
      treated with polyethylene glycol and photolithography. The properties of PDLSCs
      were investigated by flow cytometry and in vitro differentiation. PDLSC-amnion
      was transplanted into surgically created periodontal defects in rat maxillary
      molars. Periodontal regeneration was evaluated by microcomputed tomography (micro
      CT) and histological analysis. PDLSCs showed mesenchymal stem cell-like
      characteristics such as cell surface marker expression (CD90, CD44, CD73, CD105,
      CD146, and STRO-1) and trilineage differentiation ability (i.e., into
      osteoblasts, adipocytes, and chondrocytes). PDLSC-amnion exhibited a single layer
      of PDLSCs on the amniotic membrane and stability of the sheet even with movement
      and deformation caused by surgical instruments. We observed that the PDLSC-amnion
      enhanced periodontal tissue regeneration as determined by micro-CT and histology
      by 4 weeks after transplantation. These data suggest that PDLSC-amnion has
      therapeutic potential as a novel cell-based regenerative periodontal therapy. 

PMID- 24032401
TI  - Social identity complexity, cross-ethnic friendships, and intergroup attitudes in
      urban middle schools.
AB  - This study investigated contextual antecedents (i.e., cross-ethnic peers and
      friends) and correlates (i.e., intergroup attitudes) of social identity
      complexity in seventh grade. Social identity complexity refers to the perceived
      overlap among social groups with which youth identify. Identifying mostly with
      out-of-school sports, religious affiliations, and peer crowds, the ethnically
      diverse sample (N = 622; Mage in seventh grade = 12.56) showed moderately high
      complexity. Social identity complexity mediated the link between cross-ethnic
      friendships and ethnic intergroup attitudes, but only when adolescents had a high
      proportion of cross-ethnic peers at school. Results are discussed in terms of how
      school diversity can promote complex social identities and positive intergroup
      attitudes.

PMID- 24032402
TI  - Dental service mix among working-age adults in the United States, 1999 and 2009.
AB  - OBJECTIVE: In the United States, health-care costs are increasing while state and
      federal budgets contract. In order to establish a baseline and provide data for
      alternative oral health workforce models, this report describes the types of
      dental procedures received by US working-age adults in 2009 and looks at trends
      since 1999. METHODS: Data for this analysis came from the 1999 and 2009 Medical
      Expenditure Panel Surveys. The primary outcome variable represented the types of
      dental procedures undergone during a dental visit in the preceding year.
      Descriptive variables included dental insurance coverage and income. Analysis was
      restricted to adults aged 21-64 years. RESULTS: In 2009, diagnostic and
      preventive procedures accounted for >75 percent of all dental services received
      by working-age adults. Those with public insurance and those who were uninsured,
      as well as those with lower income, were less likely to receive these services
      than their peers. Between 1999 and 2009, small but statistically significant
      increases in the proportion of preventive and diagnostic procedures received
      occurred in the nation. The likelihood that a preventive service would be
      received during a visit also increased during this period, while the probability
      that a restorative procedure would be undergone went down. CONCLUSIONS:
      Preventive-type procedures represented the vast majority of dental services
      received by working-age adults in 2009. Between 1999 and 2009, receipt of
      preventive-type procedures generally increased while receipt of surgical-type
      procedures decreased. These findings emphasize the health-promoting role of the
      dental team and provide a baseline for the measurement of future trends.

PMID- 24032403
TI  - Differential regulation of CaMKIIalpha interactions with mGluR5 and NMDA
      receptors by Ca(2+) in neurons.
AB  - Two glutamate receptors, metabotropic glutamate receptor 5 (mGluR5), and
      ionotropic NMDA receptors (NMDAR), functionally interact with each other to
      regulate excitatory synaptic transmission in the mammalian brain. In exploring
      molecular mechanisms underlying their interactions, we found that Ca(2+)
      /calmodulin-dependent protein kinase IIalpha (CaMKIIalpha) may play a central
      role. The synapse-enriched CaMKIIalpha directly binds to the proximal region of
      intracellular C terminal tails of mGluR5 in vitro. This binding is state
      dependent: inactive CaMKIIalpha binds to mGluR5 at a high level whereas the
      active form of the kinase (following Ca(2+) /calmodulin binding and activation)
      loses its affinity for the receptor. Ca(2+) also promotes calmodulin to bind to
      mGluR5 at a region overlapping with the CaMKIIalpha-binding site, resulting in a
      competitive inhibition of CaMKIIalpha binding to mGluR5. In rat striatal neurons,
      inactive CaMKIIalpha constitutively binds to mGluR5. Activation of mGluR5 Ca(2+) 
      dependently dissociates CaMKIIalpha from the receptor and simultaneously promotes
      CaMKIIalpha to bind to the adjacent NMDAR GluN2B subunit, which enables
      CaMKIIalpha to phosphorylate GluN2B at a CaMKIIalpha-sensitive site. Together,
      the long intracellular C-terminal tail of mGluR5 seems to serve as a scaffolding
      domain to recruit and store CaMKIIalpha within synapses. The mGluR5-dependent
      Ca(2+) transients differentially regulate CaMKIIalpha interactions with mGluR5
      and GluN2B in striatal neurons, which may contribute to cross-talk between the
      two receptors. We show that activation of mGluR5 with a selective agonist
      triggers intracellular Ca(2+) release in striatal neurons. Released Ca(2+)
      dissociates preformed CaMKIIalpha from mGluR5 and meanwhile promotes active
      CaMKIIalpha to bind to the adjacent NMDAR GluN2B subunit, which enables
      CaMKIIalpha to phosphorylate GluN2B at a CaMKIIalpha-sensitive site. This agonist
      induced cascade seems to mediate crosstalk between mGluR5 and NMDA receptors in
      neurons. 

PMID- 24032404
TI  - Safety and efficacy of pulsed imatinib with or without G-CSF versus continuous
      imatinib in chronic phase chronic myeloid leukaemia patients at 5 years follow
      up.

PMID- 24032405
TI  - Conceptual distinctions between reflex and nonreflex precipitated seizures in the
      epilepsies: a systematic review of definitions employed in the research
      literature.
AB  - Seizure precipitation is a defining characteristic of reflex seizures and
      epilepsies, but seizure precipitants are also commonly reported for patients with
      epilepsies not considered to be reflex in nature. This raises the questions of
      exactly how reflex and nonreflex epilepsies with seizure precipitants are
      defined, and how these concepts are differentiated from one another in current
      practice. In this systematic literature review, definitions of reflex seizures,
      reflex epilepsies, and precipitation in a nonreflex context were extracted from
      published primary research papers. Content analysis was applied to these
      definitions to identify their main features, allowing comparisons to be made
      between definitions of the different concepts. Results indicated that there was
      little consistency within definitions of a given term, and that although some
      differences in definition content were found between terms, it was evident that
      clear defining characteristics to differentiate them from one another were
      lacking. These findings are discussed in the context of current debates regarding
      classification of the reflex epilepsies and the extent to which the distinction
      between reflex and nonreflex epilepsies is a meaningful one. Suggestions are made
      for how clarity might be increased in ongoing research in this area. 

PMID- 24032406
TI  - Quantum chemical and kinetics study of the thermal gas phase decomposition of 2
      chloropropene.
AB  - A detailed theoretical study of the kinetics of the thermal decomposition of 2
      chloropropene over the 600-1400 K temperature range has been done. The reaction
      takes place through the elimination of HCl with the concomitant formation of
      propyne or allene products. Relevant molecular properties of the reactant and
      transition states were calculated for each reaction channel at 14 levels of
      theory. From information provided by the BMK, MPWB1K, BB1K, M05-2X, and M06-2X
      functionals, specific for chemical kinetics studies, high-pressure limit rate
      coefficients of (5.8 +/- 1.0) * 10(14) exp[-(67.8 +/- 0.4 kcal mol(-1))/RT] s(-1)
      and (1.1 +/- 0.2) * 10(14) exp[-(66.8 +/- 0.5 kcal mol(-1))/RT] s(-1) were
      obtained for the propyne and allene channels, respectively. The pressure effect
      over the reaction was analyzed through the calculation of the low-pressure limit
      rate coefficients and falloff curves. An analysis of the branching ratio between
      the two channels as a function of pressure and temperature, based on these
      results and on computed specific rate coefficients, show that the propyne forming
      channel is predominant. 

PMID- 24032407
TI  - Tris(beta-diketonato) Ru(III) complexes as chiral dopants for nematic liquid
      crystals: the effect of the molecular structure on the helical twisting power.
AB  - Doping nematic liquid crystals with optically active compounds transforms them
      into chiral nematic phases with helical structures. In this phenomenon, the
      chirality of the dopant molecules is transferred or amplified to the bulk of the
      liquid crystals. Delta-[Ru(acac)3] (acac = acetylacetonato) is known to work as
      one of the dopants with a strong helical twisting power (HTP). In this study, we
      have systematically modified [Ru(acac)3] to clarify the correlation between the
      molecular structure and HTP; we have designed and synthesized five new Ru(III)
      complexes, [Ru(acac)2(acacC8)] (RuC8-1, acac = acetylacetonate, acacC8 = 3-(4'
      octyloxy-phenylalkynyl)-pentane-2,4-dionato), [Ru(acac)(acacC8)2] (RuC8-2),
      [Ru(acacC8)3] (RuC8-3), [Ru(acacC0)3] (RuC0-3, acacC0 = 3-(phenylalkynyl)-pentane
      2,4-dionato), and [Ru(acacC24)3] (RuC24-3, acacC24 = 3-(3',4',5'-tri(octyloxy)
      phenylalkynyl)-pentane-2,4-dionato). All the complexes, except for RuC0-3, could
      be separated into Delta, Lambda isomers by HPLC on a chiral column and were
      examined as chiral dopants for a nematic liquid crystal, N-(4-methoxybenzilidene)
      4-butylaniline (MBBA). The Delta isomers of RuC8-1, RuC8-2, RuC8-3, and RuC24-3
      induced a right-handed (P) helix and the magnitudes of the HTPs (/MUm(-1)) were
      determined as follows: RuC8-1 (+60) < RuC8-2 (+109) > RuC8-3 (+78) > RuC24-3
      (+41). The HTPs of the ruthenium dopants were not simply proportional to their
      size. The highest HTP observed in biaxial RuC8-2 was attributed to the balance of
      the molecular helicity and high ordering in MBBA based on the surface chirality
      model. 

PMID- 24032408
TI  - Fine tuning the disassembly time of thermoresponsive polymer nanoparticles.
AB  - Timed-released disassembly of nanoparticles without a remote trigger or
      environmental cues is demonstrated in this work. The reversible addition
      fragmentation chain transfer (RAFT) polymerization allowed the fine-tuning of the
      chemical composition in the diblock copolymers, in which the first block
      consisted of a hydrophilic monomer (DMA) and the second random block consisted of
      three different monomers: (a) the thermoresponsive NIPAM, (b) the self-catalyzed
      hydrolyzable DMAEA, and (c) the hydrophobic BA. These diblock copolymers were
      solubilized in water below the lower critical solution temperature (LCST) of the
      thermoresponsive second block, and heated to 37  degrees C (i.e., >LCST) to form
      small micelle nanoparticles with a narrow particle size distribution. As DMAEA
      hydrolyzed to acrylic acid groups, the LCST of the diblock increased, and the
      time at the start of micelle disassembly (t(start)) corresponded to the point
      where the LCST was equal to the solution temperature (i.e., 37  degrees C). The
      high water content in the PNIPAM core allowed an even degradation of the core
      over time. The copolymer composition allowed fine control over t(start), as this
      time was linearly dependent upon the BA units in the second block. These
      nanoparticles could also be designed to be stable (i.e., not disassemble) over a
      wide pH range or disassemble below a pH of 7.3. Additionally, the time from the
      start of disassembly to full unimer formation (t(degrade)) could be controlled by
      the amount of DMAEA units in the second block. A longer t(degrade) (~5.5 h) was
      found when the number of DMAEA units was 42 compared to t(degrade) of 1.1 h for
      25 units. The nanoparticles designed in this work, through fine control of the
      polymer chemical composition, have the potential for drug delivery purposes for
      timed-release of drugs and prodrugs and other wide-ranging applications where
      timed-release would be beneficial.

PMID- 24032409
TI  - Prenatal plumbing--vascular tissue formation in the plant embryo.
AB  - The first vascular tissue precursors are specified early during embryogenesis.
      These precursors give rise to the multi-layered cylinder of hypocotyl and root
      through controlled, oriented divisions. Concomitant with its growth, the bundle
      is patterned into xylem and phloem tissues, and intervening procambial cells.
      These patterns are later maintained during post-embryonic growth and vascular
      cells will eventually differentiate, displaying characteristic secondary cell
      wall modifications. Given that the vascular system forms de novo in a simple yet
      predictable fashion, the embryo provides an excellent model system to study early
      developmental aspects of vascular tissue formation. However, the benefits of this
      model are only beginning to be exploited, and most knowledge about the vascular
      development is derived from growing post-embryonic tissues. Importantly, it is
      unclear how much of these established post-embryonic mechanisms can be
      extrapolated to tissue formation during embryogenesis. Here we review concepts
      established in the model plant Arabidopsis thaliana and focus on recent advances
      made in understanding embryonic vascular development. 

PMID- 24032411
TI  - Authentication of fish products by large-scale comparison of tandem mass spectra.
AB  - Authentication of food is a major concern worldwide to ensure that food products
      are correctly labeled in terms of which animals are actually processed for
      consumption. Normally authentication is based on species recognition by
      comparison of selected sequences of DNA or protein. We here present a new robust,
      proteome-wide tandem mass spectrometry method for species recognition and food
      product authentication. The method does not use or require any genome sequences
      or selection of tandem mass spectra but uses all acquired data. The experimental
      steps were performed in a simple, standardized workflow including protein
      extraction, digestion, and data analysis. First, a set of reference spectral
      libraries was generated using unprocessed muscle tissue from 22 different fish
      species. Query tandem mass spectrometry data sets from "unknown" fresh muscle
      tissue samples were then searched against the reference libraries. The number of
      matching spectra could unambiguously identify the origin of all fresh samples. A
      number of processed samples were also analyzed to further test the robustness and
      applicability of the method. The results clearly show that the method is also
      able to correctly identify heavily processed samples. 

PMID- 24032410
TI  - Features of modularly assembled compounds that impart bioactivity against an RNA
      target.
AB  - Transcriptomes provide a myriad of potential RNAs that could be the targets of
      therapeutics or chemical genetic probes of function. Cell-permeable small
      molecules, however, generally do not exploit these targets, owing to the
      difficulty in the design of high affinity, specific small molecules targeting
      RNA. As part of a general program to study RNA function using small molecules, we
      designed bioactive, modularly assembled small molecules that target the noncoding
      expanded RNA repeat that causes myotonic dystrophy type 1 (DM1), r(CUG)(exp).
      Herein, we present a rigorous study to elucidate features in modularly assembled
      compounds that afford bioactivity. Different modular assembly scaffolds were
      investigated, including polyamines, alpha-peptides, beta-peptides, and peptide
      tertiary amides (PTAs). On the basis of activity as assessed by improvement of
      DM1-associated defects, stability against proteases, cellular permeability, and
      toxicity, we discovered that constrained backbones, namely, PTAs, are optimal.
      Notably, we determined that r(CUG)(exp) is the target of the optimal PTA in
      cellular models and that the optimal PTA improves DM1-associated defects in a
      mouse model. Biophysical analyses were employed to investigate potential sources
      of bioactivity. These investigations show that modularly assembled compounds have
      increased residence times on their targets and faster on rates than the RNA
      binding modules from which they were derived. Moreover, they have faster on rates
      than the protein that binds r(CUG)(exp), the inactivation of which gives rise to
      DM1-associated defects. These studies provide information about features of small
      molecules that are programmable for targeting RNA, allowing for the facile
      optimization of therapeutics or chemical probes against other cellular RNA
      targets. 

PMID- 24032412
TI  - Surface-modified silicon nanoparticles with ultrabright photoluminescence and
      single-exponential decay for nanoscale fluorescence lifetime imaging of
      temperature.
AB  - In this Communication, we report fabrication of ultrabright water-dispersible
      silicon nanoparticles (SiNPs) with quantum yields (QYs) up to 75% through a
      novelly designed chemical surface modification. A simple one-pot surface
      modification was developed that improves the photoluminescent QYs of SiNPs from
      8% to 75% and meanwhile makes SiNPs water-dispersible. Time-correlated single
      photon counting and femtosecond time-resolved photoluminescence techniques
      demonstrate the emergence of a single and uncommonly highly emissive
      recombination channel across the entire NP ensemble induced by surface
      modification. The extended relatively long fluorescence lifetime (FLT), with a
      monoexponential decay, makes such surface-modified SiNPs suitable for
      applications involving lifetime measurements. Experimental results demonstrate
      that the surface-modified SiNPs can be utilized as an extraordinary
      nanothermometer through FLT imaging. 

PMID- 24032413
TI  - Laparoscopic versus open surgery for renal masses with infrahepatic tumor
      thrombus: the largest series of retroperitoneal experience from China.
AB  - OBJECTIVE: To compare the treatment outcome of laparoscopic versus open surgery
      for renal masses with infrahepatic (levels I and II) tumor thrombus and analyze
      the largest series of retroperitoneal experience in such cases from China.
      MATERIALS AND METHODS: Forty-nine patients with renal masses with infrahepatic
      tumor thrombus were analyzed retrospectively between January 2009 and January
      2013 at our institution. The diagnosis was confirmed by computed tomography
      and/or magnetic resonance imaging preoperatively. They were divided into two
      groups based on the detailed surgical approach applied. Group 1 (A, pure
      laparoscopic; B, laparoscopic nephrectomy with open thrombectomy) consisted of 17
      patients (34.7%) and group 2 (pure open) consisted of 32 patients (65.3%).
      RESULTS: The two groups were comparable with regard to all of the patients'
      baseline characteristics. All operations were performed successfully without
      severe complications. In group 1, the mean operative time was 208.5 minutes, the
      mean estimated blood loss was 147.1 mL, the mean postoperative hospital stay was
      5.8 days, and only two patients (11.8%) accepted blood transfusion with a mean
      quantity of 300 mL. In group 2, the figures were 268.3 minutes, 1345.3 mL, 12.5
      days, respectively, and a total of 17 patients (53.1%) received transfusion with
      a mean quantity of 1488.2 mL. The differences of all these parameters were
      statistically significant between both groups (p<0.05). However, comparisons
      between the group 1A and 1B in all of the perioperative characteristics were not
      statistically significant. During a mean follow-up of 18.2 months, 13 patients in
      group 1 and 26 patients in group 2 survived. The difference in the cancer
      survival rates between both groups was not statistically significant.
      CONCLUSIONS: Although it remains technically complex, demanding and challenging
      for renal masses with infrahepatic tumor thrombus, laparoscopic surgery with a
      retroperitoneal approach can make favorable perioperative results and comparable
      survival rates in selectively less complex patients compared with the traditional
      open surgery.

PMID- 24032414
TI  - In vitro cytotoxicity and bioavailability of solid lipid nanoparticles containing
      tamoxifen citrate.
AB  - The objective of this study was to evaluate the influence of solid lipid
      nanoparticles (SLN) loaded with the poorly water-soluble drug tamoxifen citrate
      (TC) on the in vitro antitumor activity and bioavailability of the drug. TC
      loaded SLN were prepared by solvent injection method using glycerol monostearate
      (GMS) or stearic acid (SA) as lipid matrix. Poloxamer 188 or tween 80 were used
      as stabilizers. TC-loaded SLN (F3 and F4) prepared using GMS and stabilized by
      poloxamer 188 showed highest entrapment efficiency % (86.07 +/- 1.74 and 90.40 +/
      1.22%) and reasonable mean particle sizes (130.40 +/- 9.45 and 243.80 +/- 12.33
      nm), respectively. The in vitro release of TC from F3 and F4 exhibited an initial
      burst effect followed by a sustained drug release. In vitro cytotoxicity of F3
      against human breast cancer cell line MCF-7 showed comparable antitumor activity
      to free drug. Moreover, the results of bioavailability evaluation of TC-loaded
      SLN in rats compared to free TC indicated that 160.61% increase in the oral
      bioavailability of TC. The obtained results suggest that incorporation of the
      poorly water-soluble drug TC in SLN preserves the in vitro antitumor activity and
      significantly enhance oral bioavailability of TC in rats.

PMID- 24032415
TI  - Techniques for temperature monitoring during laser-induced thermotherapy: an
      overview.
AB  - Laser-induced thermotherapy (LITT) is a hyperthermic procedure recently employed
      to treat cancer in several organs. The amount of coagulated tissue depends on the
      temperature distribution around the applicator, which plays a crucial role for an
      optimal outcome: the removal of the whole neoplastic tissue, whilst preventing
      damage to the surrounding healthy tissue. Although feedback concerning tissue
      temperature could be useful to drive the physician in the adjustment of laser
      settings and treatment duration, LITT is usually performed without real-time
      monitoring of tissue temperature. During recent decades, many thermometric
      techniques have been developed to be used during thermal therapies. This paper
      provides an overview of techniques and sensors employed for temperature
      measurement during tissue hyperthermia, focusing on LITT, and an investigation of
      their performances in this application. The paper focuses on the most promising
      and widespread temperature monitoring techniques, splitting them into two groups:
      the former includes invasive techniques based on the use of thermocouples and
      fibre-optic sensors; the second analyses non-invasive methods, i.e. magnetic
      resonance imaging-, computerised tomography- and ultrasound-based thermometry.
      Background information on measuring principle, medical applications, advantages
      and weaknesses of each method are provided and discussed.

PMID- 24032416
TI  - Effects of aclidinium bromide in a cigarette smoke-exposed Guinea pig model of
      chronic obstructive pulmonary disease.
AB  - Long-acting muscarinic antagonists are widely used to treat chronic obstructive
      pulmonary disease (COPD). In addition to bronchodilation, muscarinic antagonism
      may affect pulmonary histopathological changes. The effects of long-acting
      muscarinic antagonists have not been thoroughly evaluated in experimental models
      of COPD induced by chronic exposure to cigarette smoke (CS). We investigated the
      effects of aclidinium bromide on pulmonary function, airway remodeling, and lung
      inflammation in a CS-exposed model of COPD. A total of 36 guinea pigs were
      exposed to CS and 22 were sham exposed for 24 weeks. Animals were nebulized daily
      with vehicle, 10 MUg/ml, or 30 MUg/ml aclidinium, resulting in six experimental
      groups. Pulmonary function was assessed weekly by whole-body plethysmography,
      determining the enhanced pause (Penh) at baseline, after treatment, and after
      CS/sham exposure. Lung changes were evaluated by morphometry and
      immunohistochemistry. CS exposure increased Penh in all conditions. CS-exposed
      animals treated with aclidinium showed lower baseline Penh than untreated animals
      (P = 0.02). CS induced thickening of all bronchial wall layers, airspace
      enlargement, and inflammatory cell infiltrate in airways and septa. Treatment
      with aclidinium abrogated the CS-induced smooth muscle enlargement in small
      airways (P = 0.001), and tended to reduce airspace enlargement (P = 0.054).
      Aclidinium also attenuated CS-induced neutrophilia in alveolar septa (P = 0.04).
      We conclude that, in guinea pigs chronically exposed to CS, aclidinium has an
      antiremodeling effect on small airways, which is associated with improved
      respiratory function, and attenuates neutrophilic infiltration in alveolar septa.
      These results indicate that, in COPD, aclidinium may exert beneficial effects on
      lung structure in addition to its bronchodilator action. 

PMID- 24032418
TI  - Lower groundwater 14C age by atmospheric CO2 uptake during sampling and analysis.
AB  - Uptake of atmospheric CO2 during sample collection and analysis, and consequent
      lowering of estimated ages, has rarely been considered in radiocarbon dating of
      groundwater. Using field and laboratory experiments, we show that atmospheric CO2
      can be easily and rapidly absorbed in hyperalkaline solutions used for the
      extraction of dissolved inorganic carbon, resulting in elevated 14C measurements.
      Kinetic isotope fractionation during atmospheric CO2 uptake may also result in
      decrease of delta13C, leading to insufficient corrections for addition of dead
      carbon by geochemical processes. Consequently, measured 14C values of groundwater
      should not be used for age estimation without corresponding delta13C values, and
      historical 14C data in the range of 1 to 10% modern Carbon should be re-evaluated
      to ensure that samples with atmospheric contamination are recognized
      appropriately. We recommend that samples for 14C analysis should be collected and
      processed in the field and the laboratory without exposure to the atmosphere.
      These precautions are considered necessary even if 14C measurements are made with
      an accelerator mass spectrometer.

PMID- 24032417
TI  - Observational study of ezetimibe discontinuation in primary care practices in the
      UK.
AB  - OBJECTIVE: We investigated the circumstances of ezetimibe discontinuation as its
      prescribing had been discouraged in some publications. RESEARCH DESIGN AND
      METHODS: Adults on stable lipid-modifying therapy (LMT) including ezetimibe, who
      then had >8 weeks cessation in their prescribed ezetimibe regimen (2010-2011)
      were identified from THIN UK primary care database. Lipid values and parallel
      changes to other LMT were described overall and in a sub-group with a history of
      diabetes, cardiovascular disease or familial hypercholesterolaemia (high-risk
      group). RESULTS: Ezetimibe therapy stopped in 7087 patients after a mean of 38
      months; 67.0% were in the high-risk group. No lipid readings were recorded for
      16.1% of patients in the year before and 26.2% in the year after ezetimibe
      stopped; 11.0% and 12.4% in the high-risk group respectively. In the prior year,
      60.2% patients with any lipid reading had a total cholesterol (T-cholesterol) <5
      mmol/l and 59.2% had a T-cholesterol <5 mmol/l and LDL-cholesterol <3 mmol/l. In
      the high-risk group, 66.8% had a T-cholesterol <5 mmol/l, 38.9% had either a T
      cholesterol <4 or a LDL-cholesterol <2 mmol/l and 29.4% had reached both targets.
      In both populations, 42% patients had 6 months' follow-up after ezetimibe stopped
      with no change to other LMT. An LMT change within 8 weeks (19%) was usually a new
      statin while 27% overall had a further ezetimibe prescription after 8-26 weeks.
      LIMITATIONS: Only absolute lipid values were included, as percentage change from
      baseline level may not be reliable. The study included a larger proportion of
      patients in Scotland relative to the UK population. CONCLUSIONS: Prescribed
      ezetimibe often stopped without either a recent lipid value or attainment of
      optimal, or sometimes minimum, lipid targets. Patients did not always receive
      parallel intensification of other LMT or a further ezetimibe prescription within
      6 months.

PMID- 24032419
TI  - Buckled structures and 5-azacytidine enhance cardiogenic differentiation of
      adipose-derived stem cells.
AB  - AIM: Myocardial infarction is caused after impairment of heart wall muscle
      following an immense cell loss and also when the myocardial tissue is lacking the
      inherent capacity to regenerate for normal functioning of myocardium. An
      immediate challenge in cardiac regeneration is to devise a strategy that leads to
      a reproducible degree of cardiac differentiation. We have speculated that ex vivo
      pretreatment of adipose-derived stem cells (ADSCs) using 5-azacytidine and a
      suitable patterned nanofibrous construct could lead to cardiomyogenic
      differentiation and results in superior biological and functional effects on
      cardiac regeneration of infarcted myocardium. MATERIALS & METHODS: Polyglycerol
      sebacate/gelatin fibers were fabricated by core/shell electrospinning with
      polyglycerol sebacate as the core material and gelatin as the shell material.
      Patterning of the core/shell fibers to form orthogonal and looped buckled
      nanostructures was achieved. RESULTS: Results demonstrated that the buckled
      fibers showing an orthogonal orientation and looped pattern had a Young's modulus
      of approximately 3.59 +/- 1.58 MPa and 2.07 +/- 0.44 MPa, respectively, which was
      comparable to that of native myocardium. The ADSCs cultured on these scaffolds
      demonstrated greater expression of the cardiac-specific marker proteins actinin,
      troponin and connexin 43, as well as characteristic multinucleation as shown by
      immunocytochemical and morphological analysis, indicating complete cardiogenic
      differentiation of ADSCs. CONCLUSION: In the natural milieu, cardiomyogenic
      differentiation probably involves multiple signaling pathways and we have
      postulated that a buckled structure combination of chemical treatment and
      environment-driven strategy induces cardiogenic differentiation of ADSCs. The
      combination of patterned buckled fibrous structures with stem cell biology may
      prove to be a productive device for myocardial infarction.

PMID- 24032420
TI  - Graphene-based three-dimensional hierarchical sandwich-type architecture for high
      performance Li/S batteries.
AB  - A multiwalled carbon nanotube/sulfur (MWCNT@S) composite with core-shell
      structure was successfully embedded into the interlay galleries of graphene
      sheets (GS) through a facile two-step assembly process. Scanning and transmission
      electron microscopy images reveal a 3D hierarchical sandwich-type architecture of
      the composite GS-MWCNT@S. The thickness of the S layer on the MWCNTs is ~20 nm.
      Raman spectroscopy, X-ray diffraction, thermogravimetric analysis, and energy
      dispersive X-ray analysis confirm that the sulfur in the composite is highly
      crystalline with a mass loading up to 70% of the composite. This composite is
      evaluated as a cathode material for Li/S batteries. The GS-MWCNT@S composite
      exhibits a high initial capacity of 1396 mAh/g at a current density of 0.2C (1C =
      1672 mA/g), corresponding to 83% usage of the sulfur active material. Much
      improved cycling stability and rate capability are achieved for the GS-MWCNT@S
      composite cathode compared with the composite lacking GS or MWCNT. The superior
      electrochemical performance of the GS-MWCNT@S composite is mainly attributed to
      the synergistic effects of GS and MWCNTs, which provide a 3D conductive network
      for electron transfer, open channels for ion diffusion, strong confinement of
      soluble polysulfides, and effective buffer for volume expansion of the S cathode
      during discharge.

PMID- 24032421
TI  - Simultaneous online enrichment and identification of trace species based on
      microfluidic droplets.
AB  - A facile online enrichment protocol has been proposed based on microfluidic
      droplets acting as an interface between a liquid chromatography separation system
      and detection systems of ESI-MS/MS and laser-induced fluorescence. Low-abundance
      species were successfully concentrated and analyzed in this system via droplet
      shrinkage. The proposed platform significantly increased the enrichment
      efficiency and detection sensitivity with reduced sample handling steps, short
      analysis time, and no cross-contamination. The presented system is universal,
      shows no discrimination, and is easily coupled with other separation and
      detection approaches. 

PMID- 24032422
TI  - Tandem reaction of 1-copper(I) alkynes for the synthesis of 1,4,5-trisubstituted
      5-chloro-1,2,3-triazoles.
AB  - A novel tandem reaction of 1-copper(I) alkynes with azides (cycloaddition) and
      then NCS (electrophilic substitution) was developed as an efficient method for
      the synthesis of 1,4,5-trisubstituted 5-chloro-1,2,3-triazoles. The method offers
      a rare example that a tandem reaction of an organometallic substrate does not
      involve in the reactivity of the metal-carbon bond in the first step. 

PMID- 24032424
TI  - Fibroblast cell therapy enhances initial healing in recessive dystrophic
      epidermolysis bullosa wounds: results of a randomized, vehicle-controlled trial.
AB  - BACKGROUND: Fibroblast cell therapy can modify disease biology in recessive
      dystrophic epidermolysis bullosa (RDEB) although whether it improves wound
      healing is not clear. OBJECTIVE: To assess the effects of injecting of allogeneic
      fibroblasts into the margins of chronic erosions in individuals with RDEB in a
      prospective, double-blind, randomized, vehicle-controlled phase II trial.
      METHODS: Erosions were randomized 1:1, to either a single treatment of 5 * 10(6)
      fibroblasts per linear cm of erosion margin or vehicle. All subjects continued
      standard wound care. The trial sponsor, participants and study outcome assessor
      were masked to treatment allocation. A hierarchy of endpoints germane to erosion
      closure was assessed. RESULTS: Twenty-six erosions in 11 subjects with RDEB were
      injected; 14 erosions received fibroblasts and 12 vehicle alone. A single series
      of injections was given at day 0 and all follow-up visits were completed.
      Treatment difference between fibroblasts and vehicle was -23.5% [95% confidence
      interval (CI) -3.5 to -43.5, P = 0.025] at day 7, -19.15% (95% CI 3.36 to -41.66,
      P = 0.089) at day 14 and -28.83% (95% CI 7.97 to -65.63, P = 0.11) at day 28.
      Beyond day 28, however, changes in mean erosion area did not differ significantly
      between the two groups. CONCLUSION: A single intradermal injection of allogeneic
      fibroblasts increases the initial rate of erosion healing in subjects with RDEB
      within the first 28 days but not thereafter. Further studies are needed to
      address the potential benefits of retreatment as well as optimal cell delivery.

PMID- 24032423
TI  - Non-invasive detection of neurochemical changes prior to overt pathology in a
      mouse model of spinocerebellar ataxia type 1.
AB  - Spinocerebellar ataxia type 1 (SCA1) is a hereditary, progressive and fatal
      movement disorder that primarily affects the cerebellum. Non-invasive imaging
      markers to detect early disease in SCA1 will facilitate testing and
      implementation of potential therapies. We have previously demonstrated the
      sensitivity of neurochemical levels measured by (1) H magnetic resonance
      spectroscopy (MRS) to progressive neurodegeneration using a transgenic mouse
      model of SCA1. In order to investigate very early neurochemical changes related
      to neurodegeneration, here we utilized a knock-in mouse model, the Sca1(154Q/2Q)
      line, which displays milder cerebellar pathology than the transgenic model. We
      measured cerebellar neurochemical profiles of Sca1(154Q/2Q) mice and wild-type
      littermates using 9.4T MRS at ages 6, 12, 24, and 39 weeks and assessed the
      cerebellar pathology of a subset of the mice at each time point. The
      Sca1(154Q/2Q) mice displayed very mild cerebellar pathology even at 39 weeks,
      however, were distinguished from wild types by MRS starting at 6 weeks. Taurine
      and total choline levels were significantly lower at all ages and glutamine and
      total creatine levels were higher starting at 12 weeks in Sca1(154Q/2Q) mice than
      controls, demonstrating the sensitivity of neurochemical levels to
      neurodegeneration related changes in the absence of overt pathology. We measured
      cerebellar neurochemical alterations in a knock-in mouse model of spinocerebellar
      ataxia type 1, a hereditary movement disorder, using ultra-high field magnetic
      resonance spectroscopy (MRS). Very early neurochemical alterations were
      detectable prior to overt pathology in the volume-of-interest for MRS.
      Alterations were indicative of osmolytic changes and of disturbances in membrane
      phospholipid and energy metabolism. 

PMID- 24032426
TI  - Arthroscopic-guided ulnar distraction for the correction of elbow incongruency in
      four dogs.
AB  - Four skeletally immature, small breed dogs (five elbows) with elbow incongruency
      were evaluated for forelimb lameness. Findings on clinical examination included
      pain, effusion and decreased range of motion of the affected elbow. Radiography,
      computed tomography and arthroscopy demonstrated elbow incongruency in all dogs.
      Fragmented medial coronoid process was diagnosed arthroscopically in three dogs
      (four elbows). Arthroscopic subtotal coronoidectomy was performed in all cases of
      fragmented medial coronoid process. Incongruency was corrected with acute ulnar
      lengthening under arthroscopic visualisation. The ulna was stabilised with a
      plate following correction. In two elbows an ostectomy of the anconeal process
      was performed to prevent impingement against the olecranon fossa. All dogs
      demonstrated improvement in lameness scores and client-scored visual analogue
      scale scores. Postoperative computed tomography showed significant improvement in
      elbow incongruency in all dogs. Arthroscopic-guided ulnar lengthening may be
      considered as a valid treatment in severe cases of elbow incongruency. 

PMID- 24032425
TI  - Clinical dissection of early onset absence epilepsy in children and prognostic
      implications.
AB  - PURPOSE: To investigate whether patients with typical absence seizures (TAS)
      starting in the first 3 years of life, conformed to Panayiotopoulos's definition
      of childhood absence epilepsy (CAE), show different electroclinical course than
      those not fulfilling CAE criteria. METHODS: In this multicenter retrospective
      study, we choose a fixed duration follow-up of 36 months to examine the
      electroclinical course of epilepsy in all children with TAS starting before 3
      years of age. The probands who fulfilled Panayiotopoulos's criteria for CAE were
      classified as having pure early onset absence epilepsy (P-EOAE), whereas those
      who did not as nonpure EOAE (NP-EOAE). In addition, these two groups of patients
      were further stratified according to the number of antiepileptic drugs taken to
      obtain initial seizure control (mono-, bi-, and tritherapy). KEY FINDINGS:
      Patients with P-EOAE (n = 111) showed earlier initial seizure control (p = 0.030)
      and better seizure-free survival curve (p = 0.004) than those with NP-EOAE (n =
      77). No mutation in SLC2A1 gene or abnormal neuroimaging was observed in P-EOAE.
      Among patients with NP-EOAE, those receiving tritherapy showed increased risk of
      structural brain abnormalities (p = 0.001) or SLC2A1 mutations (p = 0.001) but
      fewer myoclonic features (p = 0.031) and worse seizure-free survival curve (p =
      0.047) than those treated with mono- and bitherapy. Children with NP-EOAE had
      2.134 the odds of having relapse during the follow-up compare to those with P
      EOAE. SIGNIFICANCE: Children with early onset TAS who did meet Panayiotopoulos's
      criteria showed a favorable course of epilepsy, whereas patients not fulfilling
      Panayiotopoulos's criteria showed increased risk of relapse at long-term follow
      up.

PMID- 24032427
TI  - Effects of adrenaline on rhythm transitions in out-of-hospital cardiac arrest.
AB  - BACKGROUND: We wanted to study the effects of intravenous (i.v.) adrenaline
      (epinephrine) on rhythm transitions during cardiac arrest with initial or
      secondary ventricular fibrillation/tachycardia (VF/VT). METHODS: Post hoc
      analysis of patients included in a randomised controlled trial of i.v. drugs in
      adult, non-traumatic out-of-hospital cardiac arrest patients who were
      defibrillated and had a readable electrocardiography recording. Patients who
      received adrenaline were compared with patients who did not. Cardiac rhythms were
      annotated manually using the defibrillator data. RESULTS: Eight hundred and forty
      nine patients were included in the randomised trial of which 223 were included in
      this analysis; 119 in the adrenaline group and 104 in the no-adrenaline group.
      The proportion of patients with one or more VF/VT episodes after temporary return
      of spontaneous circulation (ROSC) was higher in the adrenaline than in the no
      adrenaline group, 24% vs. 12%, P = 0.03. Most relapses from ROSC to VF/VT in the
      no-adrenaline group occurred during the first 20 min of resuscitation, whereas
      patients in the adrenaline group experienced such relapses even after 20 min.
      Fibrillations from asystole or pulseless electrical activity, shock resistant
      VF/VT and the number of rhythm transitions per patient was higher in the
      adrenalin group compared with the no-adrenalin group: 90% vs. 69%, P < 0.001; 46%
      vs. 33%, P = 0.006; median 8 (5,13) vs. 2 (1,5), P < 0.001, respectively.
      CONCLUSION: Patients who received adrenaline had more rhythm transitions from
      ROSC and non-shockable rhythms to VF/VT.

PMID- 24032429
TI  - Structure-property relationship of amplified spontaneous emission in organic
      semiconductor materials: TPD, DPABP, and NPB.
AB  - N,N'-Diphenyl-N,N'-bis(3-methylphenyl)-(1,1'-biphenyl)-4,4'-diamine (TPD) was
      demonstrated to be suitable for stimulated emission in doping and nondoping
      planar waveguide structure, but the mechanism for its lasing is of ambiguity.
      With the aim of providing a microsscopic picture for its lasing, we performed a
      combined experimental and theortical investigation of the absorption,
      photoluminescence (PL), and stimulated emission of TPD and other two similar
      molecules: 1,4-bis (diphenylamino)biphenyl (DPABP) and N,N'-diphenyl-N,N'-bis(1
      naphthyl)-1,1'-biphenyl-4,4"-diamine (NPB). It was found that DPABP shows the
      same amplified spontaneous emission (ASE) characteristics as TPD, but NPB did
      not. In theory, density functional theory (DFT) and Franck-Condon Principle were
      used to analyze the molecular geometry in the electronic ground state as well as
      the optically excited state and the vibrational levels in electronic ground
      state, respectively. The calculation results show that for TPD and DPABP, several
      strongly elongated high-frequency modes (1199-1664 cm(-1)) in the carbon rings
      contribute to the distinct first vibronic sideband in the PL spectra, which form
      an effective four-level system for lasing. For NPB, when the peripheral toluene
      or benzene is replaced with naphthyl, a number of strongly elongated low
      frequency modes (11-689 cm(-1)) deriving from naphthyl leads to a series of
      energy sublevels, which destroys the four-level system. Our results provided a
      new insight and better understanding into the lasing of organic molecules. 

PMID- 24032428
TI  - One hundred years of grain omics: identifying the glutens that feed the world.
AB  - Glutens, the storage proteins in wheat grains, are a major source of protein in
      human nutrition. The protein composition of wheat has therefore been an important
      focus of cereal research. Proteomic tools have been used to describe the genetic
      diversity of wheat germplasms from different origins at the level of
      polymorphisms in alleles encoding glutenin and gliadin, the two main proteins of
      gluten. More recently, proteomics has been used to understand the impact of
      specific gluten proteins on wheat quality. Here we review the impact of
      proteomics on the study of gluten proteins as it has evolved from fractionation
      and electrophoretic techniques to advanced mass spectrometry. In the postgenome
      era, proteomics is proving to be essential in the effort to identify and
      understand the interactions between different gluten proteins. This is helping to
      fill in gaps in our knowledge of how the technological quality of wheat is
      determined by the interaction between genotype and environment. We also collate
      information on the various storage protein alleles identified and their
      prevalence, which makes it possible to infer the effects of wheat selection on
      grain protein content. We conclude by reviewing the more recent use of
      transgenesis aimed at improving the quality of gluten. 

PMID- 24032431
TI  - Encapsulation of a rhodamine dye within a bile acid binding protein: toward water
      processable functional bio host-guest materials.
AB  - New strategies are requested for the preparation of bioinspired host-guest
      complexes to be employed in technologically relevant applications, as sensors and
      optoelectronic devices. We report here a new approach employing a single
      monomeric protein as host for the strongly fluorescent rhodamine dye. The
      selected protein, belonging to the intracellular lipid binding protein family,
      fully encapsulates one rhodamine molecule inside its cavity forming a host-guest
      complex stabilized by H and pi-hydrogen bonds, a salt bridge, and favorable
      hydrophobic contacts, as revealed by the NMR derived structural model. The
      protein-dye solutions are easily processable and form homogeneous thin films
      exhibiting excellent photophysical and morphological properties, as derived from
      photoluminescence and AFM data. The obtained results represent the proof of
      concept of the viability of this bio host-guest system for the development of
      bioinspired optoelectronic devices. 

PMID- 24032430
TI  - Patients with chronic lymphocytic leukaemia and clonal deletion of both 17p13.1
      and 11q22.3 have a very poor prognosis.
AB  - Detection of a 17p13.1 deletion (loss of TP53) or 11q22.3 deletion (loss of ATM),
      by fluorescence in situ hybridization (FISH), in chronic lymphocytic leukaemia
      (CLL) patients is associated with a poorer prognosis. Because TP53 and ATM are
      integral to the TP53 pathway, we hypothesized that 17p13.1- (17p-) and 11q22.3-
      (11q-) occurring in the same cell (clonal 17p-/11q-) would confer a worse
      prognosis than either 17p- or 11q-. We studied 2184 CLL patients with FISH (1995
      2012) for the first occurrence of 17p-, 11q-, or clonal 17p-/11q-. Twenty (1%)
      patients had clonal 17p-/11q-, 158 (7%) had 17p- (including 4 with 17p- and 11q-
      in separate clones), 247 (11%) had 11q-, and 1759 (81%) had neither 17p- nor 11q
      . Eleven of 15 (73%) tested patients with clonal 17p-/11q- had dysfunctional TP53
      mutations. Overall survival for clonal 17p-/11q- was significantly shorter (1.9
      years) than 17p- (3.1 years, P = 0.04), 11q- (4.8 years, P <= 0.0001), or neither
      17p- nor 11q- (9.3 years, P <= 0.0001). Clonal 17p-/11q- thus conferred
      significantly worse prognosis, suggesting that loss of at least one copy of both
      TP53 and ATM causes more aggressive disease. Use of an ATM/TP53 combination FISH
      probe set could identify these very-high risk patients. 

PMID- 24032432
TI  - Probing of optical near-fields by electron Rescattering on the 1 nm scale.
AB  - We present a new method of measuring optical near-fields within ~1 nm of a metal
      surface based on rescattering of photoemitted electrons. With this method, we
      precisely measure the field enhancement factor for tungsten and gold nanotips as
      a function of tip radius. The agreement with Maxwell simulations is very good.
      Further simulations yield a field enhancement map for all materials, which shows
      that optical near-fields at nanotips are governed by a geometric effect under
      most conditions, while plasmon resonances play only a minor role. Last, we
      consider the implications of our results on quantum mechanical effects near the
      surface of nanostructures and discuss features of quantum plasmonics.

PMID- 24032434
TI  - Genotype diversity of methicillin-resistant Staphylococcus aureus in Shenyang,
      China.
AB  - BACKGROUND: The aim of this study was to better understand methicillin-resistant
      Staphylococcus aureus (MRSA) at the molecular level by investigating the
      genotypic characteristics and evolutionary patterns of MRSA clones in Shenyang,
      China. METHODS: We analyzed the molecular epidemiology of 60 MRSA isolates in
      Shenyang, China, between 2002 and 2008, using pulsed-field gel electrophoresis
      (PFGE), multilocus sequence typing (MLST), staphylococcal cassette chromosome mec
      (SCCmec) typing, and S. aureus protein A (spa) typing. They were examined for
      their antimicrobial susceptibilities. RESULTS: Among the 60 isolates, ST239 was
      identified most frequently (34 isolates; 58%), followed by ST5 (20 isolates;
      34%). Nine spa types were obtained and 4 PFGE strain families (A, B, C, and D)
      were resolved. Spa type t030, which corresponded to PFGE genotypes A1, A3, and
      A4, constituted 45% (27/60) of all isolates; spa type t037, which corresponded to
      PFGE type A2, accounted for 13% (8/60) of all isolates. These 2 spa genotypes
      belonged to ST239 and carried SCCmec type III. Isolates genotyped as spa type
      t002 comprised 27% (16/60) of the study set and included isolates typed as PFGE
      B1 and B2, ST5, and SCCmec II. Most of MRSA isolates belonging to ST239 were
      susceptible to trimethoprim-sulfamethoxazole. The minimum inhibitory
      concentration (MIC50) of vancomycin among MRSA isolates belonging to ST5 (2 mg/l)
      was higher than that for other isolates (1 mg/l). CONCLUSIONS: These data
      document 2 major epidemic MRSA clones in Shenyang, China: ST239-MRSA-SCCmec type
      III-t037/t030 and ST5-MRSA-SCCmec type II-t002.

PMID- 24032435
TI  - Recent advancements in the therapeutics of food allergy.
AB  - Food allergy is a health complication induced by certain food in the susceptible
      individuals. Due to lack of permanent cure and the global prevalence, the
      preventive approach is highly required for food allergy. Recently published
      patents have shown significant improvements in the food allergy research. In this
      review, an attempt has been done to highlight the recently developed patents
      related to the detection of allergens in food mixture. Also, patents regarding
      treatment options like use of herbal therapy, antihistamines, pre-, pro and
      synbiotics, nanocarriers, hypoallergens and several immune molecules towards
      amelioration of food allergy have been reviewed in this article. 

PMID- 24032436
TI  - Effect of pillar modules and their stoichiometry in 3D porous frameworks of
      Zn(II) with [Fe(CN)6]3-: high CO2/N2 and CO2/CH4 selectivity.
AB  - We report the synthesis, single-crystal structural characterization, and
      selective gas adsorption properties of three new 3D metal-organic frameworks of
      Zn(II), {[Zn3(bipy)3(H2O)2][Fe(CN)6]2.2(bipy).3H2O}n (1),
      {[Zn3(bipy)][Fe(CN)6]2.(C2H5OH).H2O}n (2), and
      {[Zn3(azpy)2(H2O)2][Fe(CN)6]2.4H2O}n (3) (bipy = 4,4'-bipyridyl and azpy = 4,4'
      azobipyridyl), bridged by [Fe(CN)6](3-) and exobidentate pyridyl-based linkers.
      Compounds 1-3 have been successfully isolated by varying the organic linkers
      (bipy and azpy) and their ratios during the synthesis at RT. Frameworks 1 and 3
      feature a biporous-type network. At 195 K, compounds 1-3 selectively adsorb CO2
      and completely exclude other small molecules, such as N2, Ar, O2, and CH4.
      Additionally, we have also tested the CO2 uptake capacity of 1 and 3 at ambient
      temperatures. By using the isotherms measured at 273 and 293 K, we have
      calculated the isosteric heat of CO2 adsorption, which turned out to be 35.84 and
      35.53 kJ mol(-1) for 1 and 3, respectively. Furthermore, a reasonably high heat
      of H2 adsorption (7.97 kJ mol(-1) for 1 and 7.73 kJ mol(-1) for 3) at low
      temperatures suggests strong interaction of H2 molecules with the unsaturated
      Zn(II) metal sites and as well as with the pore surface. Frameworks 1 and 3 show
      high selectivity to CO2 over N2 and CH4 at 273 K, as calculated based on the IAST
      model. The high values of DeltaH(CO2) and DeltaH(H2) stem from the preferential
      electrostatic interaction of CO2 with the unsaturated metal sites, pendent
      nitrogen atoms of [Fe(CN)6](3-), and pi-electron cloud of bipyridine aromatic
      rings as understood from first-principles density functional theory based
      calculations.

PMID- 24032433
TI  - Activation of alpha7-containing nicotinic receptors on astrocytes triggers AMPA
      receptor recruitment to glutamatergic synapses.
AB  - Astrocytes, an abundant form of glia, are known to promote and modulate synaptic
      signaling between neurons. They also express alpha7-containing nicotinic
      acetylcholine receptors (alpha7-nAChRs), but the functional relevance of these
      receptors is unknown. We show here that stimulation of alpha7-nAChRs on
      astrocytes releases components that induce hippocampal neurons to acquire more
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors post
      synaptically at glutamatergic synapses. The increase is specific in that no
      change is seen in synaptic NMDA receptor clusters or other markers for
      glutamatergic synapses, or in markers for GABAergic synapses. Moreover, the
      increases in AMPA receptors on the neuron surface are accompanied by increases in
      the frequency of spontaneous miniature synaptic currents mediated by the
      receptors and increases in the ratio of evoked synaptic currents mediated by AMPA
      versus NMDA receptors. This suggests that stimulating alpha7-nAChRs on astrocytes
      can convert 'silent' glutamatergic synapses to functional status. Astrocyte
      derived thrombospondin is necessary but not sufficient for the effect, while
      tumor necrosis factor-alpha is sufficient but not necessary. The results identify
      astrocyte alpha7-nAChRs as a novel pathway through which nicotinic cholinergic
      signaling can promote the development of glutamatergic networks, recruiting AMPA
      receptors to post-synaptic sites and rendering the synapses more functional. We
      find that activation of nicotinic receptors on astrocytes releases a component
      that specifically recruits AMPA receptors to glutamatergic synapses. The
      recruitment appears to occur preferentially at what may be 'silent synapses',
      that is, synapses that have all the components required for glutamatergic
      transmission (including NMDA receptors) but lack sufficient AMPA receptors to
      generate a response. The results are unexpected and open up new possibilities for
      mechanisms underlying network formation and synaptic plasticity. 

PMID- 24032437
TI  - Cognitive behavior therapy for depression in people with epilepsy: a systematic
      review.
AB  - Cognitive behavioral therapy (CBT) is a recommended treatment for depression in
      people with epilepsy (PWE); however, a recent Cochrane review found that there
      was insufficient evidence that any psychological therapy is effective. This
      conclusion provides little help to clinicians who provide interventions for
      depressed PWE. The aim of this review was to systematically and qualitatively
      review the literature on the efficacy of CBT for depression in PWE based on
      randomized controlled trials (RCTs) and case series. We aim to determine patterns
      in the literature to inform the type of CBT, if any, that should be offered to
      PWE who are depressed. Databases MEDLINE, PsycINFO, and the Cochrane EBM Reviews
      were searched via OVID. Selection criteria included the following: (1)
      participants with epilepsy; (2) use of CBT; (3) valid depression outcome measure;
      and (4) published in peer-reviewed journal in English. Inclusions of studies were
      assessed by two independent researchers. We identified 14 outcome papers for 13
      CBT trials including 6 randomized controlled trials (RCTs) and 7 case series.
      Positive effects of CBT on depression were reported in three of six RCTs. A
      review of their content revealed that all effective RCTs specifically tailored
      CBT to improve depression. Conversely, two of three RCTs that failed to find
      depression-related effects focused on improving seizure-control. This pattern was
      also observed in the case series. Although limited in number and having
      methodologic limitations, the treatment studies included in our review suggest
      that interventions tailored toward improving depression are possibly efficacious,
      whereas those that focus on improving seizure control do not appear to be.
      However, this review highlights that there is need for further RCTs in this area
      in order to confirm the possible efficacy of CBT for depression in PWE.

PMID- 24032438
TI  - Can obese stone formers follow dietary recommendations?
AB  - INTRODUCTION: Obese patients have an increased risk of kidney stones, and several
      studies have identified specific urinary derangements on 24-hour collections. The
      objective of this study was to assess obese and super-obese stone formers, and
      their compliance with dietary modifications over time, based on 24-hour urine
      outcomes. PATIENTS AND METHODS: A retrospective review was performed searching
      for all stone formers who completed a 24-hour urine collection before and after
      dietary counseling for stone prevention. Patients were excluded if placed on
      medical therapy in addition to dietary therapy. Patients were divided in three
      main groups according to their body mass index (BMI): 30, 30-40, and >40 kg/m(2).
      Demographic data and 24-hour urine stone risk parameters (volume, sodium, uric
      acid, citrate, and oxalate) were assessed. Initial 24-hour urine results were
      compared to follow-up results after dietary counseling. Then, the outcomes from
      each group were compared to each other. RESULTS: Two hundred and fourteen stone
      formers (67% male) were identified with a mean age of 49.5+/-15.0 years. One
      hundred twenty-eight (59.8%) patients had BMI <30 kg/m(2), 61 (28.5%) between 30
      40 kg/m(2), and 25 (11.7%) >40 kg/m(2). Among patients with BMI <30 kg/m(2),
      there were significant improvements in all urinary parameters (p<0.001) as well
      as in the group with BMI between 30 to 40 kg/m(2) (p=0.02 for oxalate, p<0.001
      for other parameters). Among super-obese patients, there were significant
      improvements in the urinary volume (p=0.03), sodium (p<0.001), uric acid
      (p=0.001), and oxalate (p<0.001). There were no significant differences in the
      improvements observed in the urinary volume (p=0.69), sodium (p=0.08), uric acid
      (p=0.17), and citrate levels (p=0.97) between the groups. CONCLUSION: Dietary
      recommendations can be an equally effective strategy in decreasing the risk or
      stone recurrence in obese and super-obese kidney stone formers as it is in those
      who are not obese.

PMID- 24032440
TI  - The WHI: have our worst fears come true?

PMID- 24032439
TI  - Monothiol glutaredoxins can bind linear [Fe3S4]+ and [Fe4S4]2+ clusters in
      addition to [Fe2S2]2+ clusters: spectroscopic characterization and functional
      implications.
AB  - Saccharomyces cerevisiae mitochondrial glutaredoxin 5 (Grx5) is the archetypical
      member of a ubiquitous class of monothiol glutaredoxins with a strictly conserved
      CGFS active-site sequence that has been shown to function in biological
      [Fe2S2](2+) cluster trafficking. In this work, we show that recombinant S.
      cerevisiae Grx5 purified aerobically, after prolonged exposure of the cell-free
      extract to air or after anaerobic reconstitution in the presence of glutathione,
      predominantly contains a linear [Fe3S4](+) cluster. The excited-state electronic
      properties and ground-state electronic and vibrational properties of the linear
      [Fe3S4](+) cluster have been characterized using UV-vis absorption/CD/MCD, EPR,
      Mossbauer, and resonance Raman spectroscopies. The results reveal a rhombic S =
      5/2 linear [Fe3S4](+) cluster with properties similar to those reported for
      synthetic linear [Fe3S4](+) clusters and the linear [Fe3S4](+) clusters in purple
      aconitase. Moreover, the results indicate that the Fe-S cluster content
      previously reported for many monothiol Grxs has been misinterpreted exclusively
      in terms of [Fe2S2](2+) clusters, rather than linear [Fe3S4](+) clusters or
      mixtures of linear [Fe3S4](+) and [Fe2S2](2+) clusters. In the absence of GSH,
      anaerobic reconstitution of Grx5 yields a dimeric form containing one [Fe4S4](2+)
      cluster that is competent for in vitro activation of apo-aconitase, via intact
      cluster transfer. The ligation of the linear [Fe3S4](+) and [Fe4S4](2+) clusters
      in Grx5 has been assessed by spectroscopic, mutational, and analytical studies.
      Potential roles for monothiol Grx5 in scavenging and recycling linear [Fe3S4](+)
      clusters released during protein unfolding under oxidative stress conditions and
      in maturation of [Fe4S4](2+) cluster-containing proteins are discussed in light
      of these results. 

PMID- 24032441
TI  - Vitamins and bone health in women.

PMID- 24032442
TI  - Calcitriol enhances 5-aminolevulinic acid-induced fluorescence and the effect of
      photodynamic therapy in human glioma.
AB  - BACKGROUND: Glioma recurrence frequently occurs close to the marginal area of the
      surgical cavity as a result of residual infiltrating glioma cells. Fluorescence
      guided surgery with 5-aminolevulinic acid (ALA) for resection of gliomas has been
      used as an effective therapeutic approach to discriminate malignant tissue from
      brain tissue and to facilitate patient prognosis. ALA-based photodynamic therapy
      is an effective adjuvant treatment modality for gliomas. However, insufficient
      protoporphyrin IX (PpIX) accumulation may limit the applicability of fluorescence
      guided resection and photodynamic therapy in the marginal areas of gliomas.
      METHODS: To be able to understand how to overcome these issues, human glioma
      cells and normal astrocytes were used as the model system. Glioma cells and
      astrocytes were preconditioned with calcitriol for 48 hours and then incubated
      with ALA. Changes in ALA-induced PpIX fluorescence and cell survival after light
      exposure were assessed. Furthermore, expression of porphyrin synthetic enzymes in
      pretreated glioma cells was analyzed. RESULTS: Calcitriol can be administered
      prior to ALA as a non-toxic preconditioning regimen to significantly enhance ALA
      induced PpIX levels and fluorescence. This increase in PpIX level was detected
      preferentially in glioma versus normal cells. Also, calcitriol pretreated glioma
      cells exhibited increased cell death following ALA-based photodynamic therapy.
      Furthermore, mechanistic studies documented that expression of the porphyrin
      synthesis enzymes coproporphyrinogen oxidase was increased by calcitriol at the
      mRNA level. CONCLUSION: We demonstrated for the first time a simple, non-toxic
      and highly effective preconditioning regimen to selectively enhance PpIX
      fluorescence and the response of ALA-PDT in glioma cells. This finding suggests
      that the combined treatment of glioma cells with calcitriol plus ALA may provide
      an effective and selective therapeutic modality to enhance ALA-induced PpIX
      fluorescent quality for improving discrimination of tumor tissue and PDT
      efficacy.

PMID- 24032443
TI  - Dose-adapted salvage radiotherapy after radical prostatectomy based on an erMRI
      target definition model: toxicity analysis.
AB  - BACKGROUND: To assess treatment tolerance by patients treated with a dose-adapted
      salvage radiotherapy (SRT) protocol based on an multiparametric endorectal
      magnetic resonance imaging (erMRI) failure definition model after radical
      prostatectomy (RP). MATERIAL AND METHODS: A total of 171 prostate cancer patients
      recurring after RP undergoing erMRI before SRT were analyzed. A median dose of 64
      Gy was delivered to the prostatic bed (PB) with, in addition, a boost of 10 Gy to
      the suspected relapse as visualized on erMRI in 131 patients (76.6%).
      Genitourinary (GU) and gastrointestinal (GI) toxicities were scored using the
      RTOG scale. RESULTS: Grade >= 3 GU and GI acute toxicity were observed in three
      and zero patients, respectively. The four-year grade >= 2 and >= 3 late GU and GI
      toxicity-free survival rates (109 patients with at least two years of follow-up)
      were 83.9 +/- 4.7% and 87.1 +/- 4.2%, and 92.1 +/- 3.6% and 97.5 +/- 1.7%,
      respectively. Boost (p = 0.048) and grade >= 2 acute GU toxicity (p = 0.008) were
      independently correlated with grade >= 2 late GU toxicity on multivariate
      analysis. CONCLUSIONS: A dose-adapted, erMRI-based SRT approach treating the PB
      with a boost to the suspected local recurrence may potentially improve the
      therapeutic ratio by selecting patients that are most likely expected to benefit
      from SRT doses above 70 Gy as well as by reducing the size of the highest-dose
      target volume. Further prospective trials are needed to investigate the use of
      erMRI in SRT as well as the role of dose-adapted protocols and the best
      fractionation schedule.

PMID- 24032444
TI  - Vitamin C prevents cigarette smoke-induced pulmonary emphysema in mice and
      provides pulmonary restoration.
AB  - Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis.
      We investigated whether VC treatment prevents and cures smoke-induced emphysema
      in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize
      VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the
      first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l)
      [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to
      cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed
      when the mice were 6 months of age. The second study began after the
      establishment of smoke-induced emphysema (a treatment study). These mice no
      longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2
      months. Morphometric analysis was performed, and measurements of oxidative
      stress, collagen synthesis, and vascular endothelial growth factor in the lungs
      were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean
      linear intercepts [MLI] and 106.5% increases of destructive index compared with
      the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely
      resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema
      persisted in the VC(L) group after smoking cessation, whereas VC treatment
      provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of
      destructive index compared with VC(L) group). VC treatment diminished oxidative
      stress, increased collagen synthesis, and improved vascular endothelial growth
      factor levels in the lungs. Our results suggest that VC not only prevents smoke
      induced emphysema in SMP30-KO mice but also restores emphysematous lungs.
      Therefore, VC may provide a new therapeutic strategy for treating chronic
      obstructive pulmonary disease in humans. 

PMID- 24032445
TI  - Characteristics of groundwater recharge on the North China Plain.
AB  - Groundwater recharge is an important component of the groundwater system. On the
      North China Plain (NCP), groundwater is the main water supply. Because of large
      scale overexploitation, the water table has declined, which has produced severe
      adverse effects on the environment and ecosystem. In this article, tracer
      experiment and watershed model were used to calculate and analyze NCP groundwater
      recharge. In the tracer experiment, average recharge was 108 mm/year and recharge
      coefficient 0.16. With its improved irrigation, vegetation coverage and
      evapotranspiration modules, the INFIL3.0 model was used for calculation of
      groundwater recharge. Regional modeling results showed an average recharge of 102
      mm/year and recharge coefficient 0.14, for 2001-2009. These values are very
      similar to those from the field tracer experiment. Influences in the two methods
      were analyzed. The results can provide an important reference for NCP groundwater
      recharge. 

PMID- 24032446
TI  - Enhancement of anion binding in lanthanide optical sensors.
AB  - In the design of molecular sensors, researchers exploit binding interactions that
      are usually defined in terms of topology and charge complementarity. The
      formation of complementary arrays of highly cooperative, noncovalent bonding
      networks facilitates protein-ligand binding, leading to motifs such as the "lock
      and-key". Synthetic molecular sensors often employ metal complexes as key design
      elements as a way to construct a binding site with the desired shape and charge
      to achieve target selectivity. In transition metal complexes, coordination
      number, structure and ligand dynamics are governed primarily by a combination of
      inner-sphere covalent and outer-sphere noncovalent interactions. These
      interactions provide a rich variable space that researchers can use to tune
      structure, stability, and dynamics. In contrast, lanthanide(III)-ligand complex
      formation and ligand-exchange dynamics are dominated by reversible electrostatic
      and steric interactions, because the unfilled f shell is shielded by the larger,
      filled d shell. Luminescent lanthanides such as terbium, europium, dysprosium,
      and samarium display many photophysical properties that make them excellent
      candidates for molecular sensor applications. Complexes of lanthanide ions act as
      receptors that exhibit a detectable change in metal-based luminescence upon
      binding of an anion. In our work on sensors for detection of dipicolinate, the
      unique biomarker of bacterial spores, we discovered that the incorporation of an
      ancillary ligand (AL) can enhance binding constants of target anions to
      lanthanide ions by as much as two orders of magnitude. In this Account, we show
      that selected ALs in lanthanide/anion systems greatly improve sensor performance
      for medical, planetary science, and biodefense applications. We suggest that the
      observed anion binding enhancement could result from an AL-induced increase in
      positive charge at the lanthanide ion binding site. This effect depends on
      lanthanide polarizability, which can be established from the ionization energy of
      Ln(3+) -> Ln(4+). These results account for the order Tb(3+) > Dy(3+) > Eu(3+) ~
      Sm(3+). As with many lanthanide properties, ranging from hydration enthalpy to
      vaporization energy, this AL-induced enhancement shows a large discrepancy
      between Tb(3+) and Eu(3+) despite their similarity in size, a phenomenon known as
      the "gadolinium break". This discrepancy, based on the unusual stabilities of the
      Eu(2+) and Tb(4+) oxidation states, results from the half-shell effect, as both
      of these ions have half-filled 4f-shells. The high polarizability of Tb(3+)
      explains the extraordinarily large increase in the binding affinity of anions for
      terbium compared to other lanthanides. We recommend that researchers consider
      this AL-induced enhancement when designing lanthanide-macrocycle optical sensors.
      Ancillary ligands also can reduce the impact of interfering species such as
      phosphate commonly found in environmental and physiological samples. 

PMID- 24032449
TI  - Calculating osmotic pressure of xylitol solutions from molality according to
      UNIFAC model and measuring it with air humidity osmometry.
AB  - The osmotic pressure of xylitol solution at a wide concentration range was
      calculated according to the UNIFAC model and experimentally determined by our
      newly reported air humidity osmometry. The measurements from air humidity
      osmometry were compared with UNIFAC model calculations from dilute to saturated
      solution. Results indicate that air humidity osmometry measurements are
      comparable to UNIFAC model calculations at a wide concentration range by two one
      sided test and multiple testing corrections. The air humidity osmometry is
      applicable to measure the osmotic pressure and the osmotic pressure can be
      calculated from the concentration.

PMID- 24032447
TI  - Overexpression of CaWRKY27, a subgroup IIe WRKY transcription factor of Capsicum
      annuum, positively regulates tobacco resistance to Ralstonia solanacearum
      infection.
AB  - WRKY proteins are encoded by a large gene family and are linked to many
      biological processes across a range of plant species. The functions and
      underlying mechanisms of WRKY proteins have been investigated primarily in model
      plants such as Arabidopsis and rice. The roles of these transcription factors in
      non-model plants, including pepper and other Solanaceae, are poorly understood.
      Here, we characterize the expression and function of a subgroup IIe WRKY protein
      from pepper (Capsicum annuum), denoted as CaWRKY27. The protein localized to
      nuclei and activated the transcription of a reporter GUS gene construct driven by
      the 35S promoter that contained two copies of the W-box in its proximal upstream
      region. Inoculation of pepper cultivars with Ralstonia solanacearum induced the
      expression of CaWRKY27 transcript in 76a, a bacterial wilt-resistant pepper
      cultivar, whereas it downregulated the expression of CaWRKY27 transcript in Gui-1
      3, a bacterial wilt-susceptible pepper cultivar. CaWRKY27 transcript levels were
      also increased by treatments with salicylic acid (SA), methyl jasmonate (MeJA)
      and ethephon (ETH). Transgenic tobacco plants overexpressing CaWRKY27 exhibited
      resistance to R. solanacearum infection compared to that of wild-type plants.
      This resistance was coupled with increased transcript levels in a number of
      marker genes, including hypersensitive response genes, and SA-, JA- and ET
      associated genes. By contrast, virus-induced gene silencing (VIGS) of CaWRKY27
      increased the susceptibility of pepper plants to R. solanacearum infection. These
      results suggest that CaWRKY27 acts as a positive regulator in tobacco resistance
      responses to R. solanacearum infection through modulation of SA-, JA- and ET
      mediated signaling pathways. 

PMID- 24032448
TI  - Measurement of delta18O, delta17O, and 17O-excess in water by off-axis integrated
      cavity output spectroscopy and isotope ratio mass spectrometry.
AB  - Stable isotopes of water have long been used to improve understanding of the
      hydrological cycle, catchment hydrology, and polar climate. Recently, there has
      been increasing interest in measurement and use of the less-abundant (17)O
      isotope in addition to (2)H and (18)O. Off-axis integrated cavity output
      spectroscopy (OA-ICOS) is demonstrated for accurate and precise measurements
      delta(18)O, delta(17)O, and (17)O-excess in liquid water. OA-ICOS involves no
      sample conversion and has a small footprint, allowing measurements to be made by
      researchers collecting the samples. Repeated (514) high-throughput measurements
      of the international isotopic reference water standard Greenland Ice Sheet
      Precipitation (GISP) demonstrate the precision and accuracy of OA-ICOS:
      delta(18)OVSMOW-SLAP = -24.74 +/- 0.070/00 (1sigma) and delta(17)OVSMOW-SLAP = 
      13.12 +/- 0.050/00 (1sigma). For comparison, the International Atomic Energy
      Agency (IAEA) value for delta(18)OVSMOW-SLAP is -24.76 +/- 0.090/00 (1sigma) and
      an average of previously reported values for delta(17)OVSMOW-SLAP is -13.12 +/-
      0.060/00 (1sigma). Multiple (26) high-precision measurements of GISP provide a
      (17)O-excessVSMOW-SLAP of 23 +/- 10 per meg (1sigma); an average of previously
      reported values for (17)O-excessVSMOW-SLAP is 22 +/- 11 per meg (1sigma). For all
      these OA-ICOS measurements, precision can be further enhanced by additional
      averaging. OA-ICOS measurements were compared with two independent isotope ratio
      mass spectrometry (IRMS) laboratories and shown to have comparable accuracy and
      precision as the current fluorination-IRMS techniques in delta(18)O, delta(17)O,
      and (17)O-excess. The ability to measure accurately delta(18)O, delta(17)O, and
      (17)O-excess in liquid water inexpensively and without sample conversion is
      expected to increase vastly the application of delta(17)O and (17)O-excess
      measurements for scientific understanding of the water cycle, atmospheric
      convection, and climate modeling among others. 

PMID- 24032450
TI  - Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)
      gamma chain (-) (NRG) mice is similar but not identical to the original stem cell
      donor.
AB  - The murine immune system is not necessarily identical to it human counterpart,
      which has led to the construction of humanized mice. The current study analysed
      whether or not a human immune system contained within the non-obese diabetic
      (NOD)-Rag1(null) -gamma chain(null) (NRG) mouse model was an accurate
      representation of the original stem cell donor and if multiple mice constructed
      from the same donor were similar to one another. To that end, lightly irradiated
      NRG mice were injected intrahepatically on day 1 of life with purified cord blood
      derived CD34(+) stem and progenitor cells. Multiple mice were constructed from
      each cord blood donor. Mice were analysed quarterly for changes in the immune
      system, and followed for periods up to 12 months post-transplant. Mice from the
      same donor were compared directly with each other as well as with the original
      donor. Analyses were performed for immune reconstitution, including flow
      cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was
      observed that NRG mice could be 'humanized' long-term using cord blood stem
      cells, and that animals constructed from the same cord blood donor were nearly
      identical to one another, but quite different from the original stem cell donor
      immune system. 

PMID- 24032451
TI  - Fluxional cyclic seleninate ester: NMR and computational studies, glutathione
      peroxidase-like behavior, and unexpected rearrangement.
AB  - The oxidation of allyl selenide 12 with hydrogen peroxide produced the
      corresponding allyl selenurane 14, the cyclic seleninate ester 4, or the
      rearranged O-allyl seleninate ester 18, dependng on the conditions. Crossover
      experiments with selenide 12 and its deuterated crotyl analogue 27 indicated an
      intramolecular rearrangement that proceeds by an intramolecular pathway where the
      allyl or crotyl group is translocated via its distal carbon atom to the
      hydroxymethyl functionality. Variable-temperature NMR experiments with cyclic
      seleninate ester 4 revealed fluxional behavior at room temperature that was
      catalyzed by trifluoroacetic acid. Computational studies indicated an activation
      energy of 12.3 kcal mol(-1) for hydroxyl interchange at selenium, comparable to
      the value of 15.5 kcal mol(-1) derived from the NMR experiments. The glutathione
      peroxidase-like activity of 4 was measured in an assay where the catalysis of the
      reduction of hydrogen peroxide with benzyl thiol was monitored by the appearance
      of dibenzyl disulfide. The catalytic activity of 4 was double that observed with
      the unsubstituted seleninate ester 2 but was limited by the competing
      accumulation of the relatively inert selenenyl sulfide 32, resulting in a
      deactivation pathway that competes with the primary catalytic cycle. 

PMID- 24032452
TI  - Potassium bromide-associated panniculitis.
AB  - Two cases of panniculitis associated with administration of potassium bromide in
      dogs are reported. Both dogs were treated with potassium bromide for idiopathic
      epilepsy for over 1 year. Dose increases in both cases were associated with
      panniculitis, characterised by painful subcutaneous nodules in a generalised
      distribution over the trunk. Nodule eruption waxed and waned in one dog and was
      persistent in the other. In both cases, panniculitis was accompanied by lethargy
      and pyrexia. Panniculitis, lethargy and pyrexia resolved and failed to recur
      after discontinuation of potassium bromide. No other cause of panniculitis could
      be determined for either dog. Panniculitis has been reported after administration
      of potassium bromide in humans and may be a form of drug-induced erythema
      nodosum. To the authors' knowledge, these are the first reports of potassium
      bromide-associated panniculitis in dogs. 

PMID- 24032453
TI  - Dependent and paranoid personality patterns in myotonic dystrophy type 1.
AB  - OBJECTIVES: To analyze frequency and type of personality pattern in patients with
      myotonic dystrophy type 1 (DM1), to correlate these findings with clinical data,
      and to assess its possible influence on quality of life (QoL). MATERIALS AND
      METHODS: This cross-sectional study comprised 62 patients with DM1. Following
      measures were used: Muscular Impairment Rating Scale, Raven's Standard
      Progressive Matrices (RSPM), Millon Multiaxial Clinical Inventory I (MMCI), SF
      36, and Individualized Neuromuscular Quality of Life (INQoL) questionnaires.
      RESULTS: The presence of at least one pathological personality trait with score
      above 85 on MMCI was found in 47 (75.8%) patients. After clinical interview, 36
      (58.1%) subjects had significant personality impairment. The most common
      personality trait in our cohort of patients was dependent found in 51.6% of
      patients, followed by paranoid (38.7%). Higher score on dependent personality
      scale correlated with lower education (rho = -0.251, P = 0.049). Dependent
      personality scores significantly differed between patients with physical and
      intellectual work (93.1 +/- 8.9 vs 66.9 +/- 31.7, P = 0.011). Paranoid score was
      higher in patients with lower education (rho = -0.293, P = 0.021), lower score on
      RSPM test (rho = -0.398, P = 0.004) and larger number of CTG repeats (rho =
      0.254, P = 0.046). Presence of dependent personality was not in association with
      QoL scores (P > 0.05). On the other hand, patients with paranoid personality
      trait had worse QoL than those without it (P < 0.05). CONCLUSION: Almost 60% of
      our patients with DM1 had clinically significant personality impairment, with
      dependent and paranoid personality patterns being the most common. Paranoid
      personality may decrease QoL in these patients, which gives us new opportunities
      for symptomatic therapy in DM1.

PMID- 24032454
TI  - Proteomics in deciphering the auxin commitment in the Arabidopsis thaliana root
      growth.
AB  - The development of plant root systems is characterized by a high plasticity, made
      possible by the continual propagation of new meristems. Root architecture is
      fundamental for overall plant growth, abiotic stress resistance, nutrient uptake,
      and response to environmental changes. Understanding the function of genes and
      proteins that control root architecture and stress resistance will contribute to
      the development of more sustainable systems of intensified crop production. To
      meet these challenges, proteomics provide the genome-wide scale characterization
      of protein expression pattern, subcellular localization, post-translational
      modifications, activity regulation, and molecular interactions. In this review,
      we describe a variety of proteomic strategies that have been applied to study the
      proteome of the whole organ and of specific cell types during root development.
      Each has advantages and limitations, but collectively they are providing
      important insights into the mechanisms by which auxin structures and patterns the
      root system and into the interplay between signaling networks, auxin transport
      and growth. The acquisition of proteomic, transcriptomic, and metabolomic data
      sets of the root apex on the cell scale has revealed the high spatial complexity
      of regulatory networks and fosters the use of new powerful proteomic tools for a
      full understanding of the control of root developmental processes and
      environmental responses. 

PMID- 24032455
TI  - Comment on "Coherence and uncertainty in nanostructured organic photovoltaics".

PMID- 24032457
TI  - Poly(ethylene glycol) conjugation stabilizes the secondary structure of alpha
      helices by reducing peptide solvent accessible surface area.
AB  - We investigate the effect of poly(ethylene glycol) (PEG) side-chain conjugation
      on the conformational behavior of an alpha-helix using molecular dynamics
      simulations in explicit solvents of varying hydrophobicity. Our simulations
      illustrate an increase in peptide helicity with increasing PEG molecular weight
      in the range ~400 to 1800 Da. The data with varying PEG contour lengths as well
      as constant force pulling simulations that allow control over the end-to-end
      length of PEG indicate a strong inverse correlation between peptide helicity and
      solvent accessible surface area (SASA). A residue-based mapping analysis reveals
      that the formation of a protecting PEG shell around peptide helix in water is
      facilitated by two distinct mechanisms that depend on the solvent environment.
      First, cationic residues such as lysine interact favorably with PEG due to strong
      polar interactions with PEG oxygen atoms. Additionally, we find that hydrophobic
      residues interact strongly with PEG to reduce their SASA in polar solvents by
      polymer shielding. Our simulations illustrate that these two mechanisms that
      involve side-chain chemistry and solvent polarity govern the preferred
      conformation of PEG on the helix surface and thus the stability of peptide
      secondary structure. These findings elucidate the molecular mechanisms
      underpinning recent experimental findings on the stability and conformational
      dynamics of protein-PEG conjugates.

PMID- 24032456
TI  - A multicentre, phase II trial of ofatumumab monotherapy in relapsed/progressive
      diffuse large B-cell lymphoma.
AB  - This international, multicentre phase II study was conducted to assess
      ofatumumab, a human anti-CD20 monoclonal antibody, in patients with
      relapsed/progressive diffuse large B-cell lymphoma (DLBCL) who were ineligible
      for autologous stem cell transplantation (TI) or who had relapse/progression
      after transplantation (PT). Eighty-one patients received ofatumumab 300 mg
      intravenously (IV) on Day 1, followed by seven weekly IV infusions of 1000 mg.
      Patients in the TI and PT groups had received a median of 3 (range, 1-7) and 5
      (range, 2-7) prior therapies, respectively. One-third of patients did not respond
      to the last prior therapy, and 53% had failed two or more rituximab-containing
      therapies. Overall response rate was 13% for the TI group (seven partial
      responses) and 8% for the PT group (two complete responses). Median progression
      free survival was 2.6 months, and median duration of response was 9.5 months. The
      most common Grade 3-4 adverse events were neutropenia (11%), leucopenia (6%),
      lymphopenia (6%) and thrombocytopenia (6%). Sixteen deaths have been reported,
      with disease progression as the most common cause of death. In conclusion,
      ofatumumab monotherapy was well tolerated and provided clinical benefit to some
      DLBCL patients in this study.

PMID- 24032458
TI  - Local atomic and electronic structure of boron chemical doping in monolayer
      graphene.
AB  - We use scanning tunneling microscopy and X-ray spectroscopy to characterize the
      atomic and electronic structure of boron-doped and nitrogen-doped graphene
      created by chemical vapor deposition on copper substrates. Microscopic
      measurements show that boron, like nitrogen, incorporates into the carbon lattice
      primarily in the graphitic form and contributes ~0.5 carriers into the graphene
      sheet per dopant. Density functional theory calculations indicate that boron
      dopants interact strongly with the underlying copper substrate while nitrogen
      dopants do not. The local bonding differences between graphitic boron and
      nitrogen dopants lead to large scale differences in dopant distribution. The
      distribution of dopants is observed to be completely random in the case of boron,
      while nitrogen displays strong sublattice clustering. Structurally, nitrogen
      doped graphene is relatively defect-free while boron-doped graphene films show a
      large number of Stone-Wales defects. These defects create local electronic
      resonances and cause electronic scattering, but do not electronically dope the
      graphene film.

PMID- 24032459
TI  - Chronic inhibition of cGMP-specific phosphodiesterase 5 suppresses endoplasmic
      reticulum stress in heart failure.
AB  - BACKGROUND AND PURPOSE: Inhibition of the cGMP-specific phosphodiesterase 5
      (PDE5) exerts profound beneficial effects on failing hearts. However, the
      mechanisms underlying the therapeutic effects of PDE5 inhibition on heart failure
      are unclear. The purpose of this study was to investigate whether PDE5 inhibition
      decreases endoplasmic reticulum (ER) stress, a key event in heart failure.
      EXPERIMENTAL APPROACH: Heart failure was induced by isoprenaline s.c. injection
      in Sprague-Dawley rats and transverse aortic constriction (TAC) in mice. PDE5 was
      inhibited with sildenafil. Heart function was detected by invasive pressure
      volume analysis and echocardiography. ER stress markers were analysed by Western
      blotting. Apoptosis was measured by flow cytometric analysis. KEY RESULTS: PDE5
      inhibition markedly attenuated isoprenaline-induced and TAC-induced cardiac
      hypertrophy and dysfunction, and reduced ER stress and apoptosis. Further, PDE5
      inhibition with sildenafil largely prevented ER stress and reduced apoptosis in
      isoprenaline- or thapsigargin-treated cardiomyocytes. PKG inhibition markedly
      prevented the protective effects of sildenafil in vivo and in vitro. To further
      understand the mechanism of the effect of PDE5 inhibition on ER stress, we
      demonstrated that PDE5 inhibitor increased sarco-(endo)-plasmic reticulum Ca(2+) 
      ATPase activity via phosphorylation of phospholamban at Ser(16) . This may
      contribute to the attenuation of ER stress induced by PDE5 inhibition. CONCLUSION
      AND IMPLICATIONS: These results suggest that PDE5 inhibition can attenuate ER
      stress and improve cardiac function in vivo and in vitro. Suppression of ER
      stress by inhibiting PDE5 may contribute to the therapeutic effects on heart
      failure.

PMID- 24032461
TI  - Conformation control of abiotic alpha-helical foldamers.
AB  - With the aim to find new protein-protein inhibitors, a three part methodology was
      applied to oligophenylpyridines. Theoretical ring twist angle predictions have
      been validated by X-ray diffraction and molecular dynamics simulations with NMR
      constraints. Careful choice of substituent and nitrogen positions in
      oligophenylpyridyl foldamer units opens the way to conformational control of the
      side chain distribution of this alpha-helix mimic. 

PMID- 24032460
TI  - Alternative polyadenylation and miR-34 family members regulate tau expression.
AB  - Tau pathologically aggregates in Alzheimer's disease, and evidence suggests that
      reducing tau expression may be safe and beneficial for the prevention or
      treatment of this disease. We sought to examine the role of the 3'-untranslated
      region (3'-UTR) of human tau mRNA in regulating tau expression. Tau expresses two
      3'-UTR isoforms, long and short, as a result of alternative polyadenylation.
      Using luciferase reporter constructs, we found that expression from these
      isoforms is differentially controlled in human neuroblastoma cell lines M17D and
      SH-SY5Y. Several microRNAs were computationally identified as candidates that
      might bind the long, but not short, tau 3'-UTR isoform. A hit from a screen of
      candidates, miR-34a, was subsequently shown to repress the expression of
      endogenous tau protein in M17D cells. Conversely, inhibition of endogenously
      expressed miR-34 family members leads to increased endogenous tau expression. In
      addition, through an unbiased screen of fragments of the human tau 3'-UTR using a
      luciferase reporter assay, we identified several other regions in the long tau 3'
      UTR isoform that contain regulatory cis-elements. Improved understanding of the
      regulation of tau expression by its 3'-UTR may ultimately lead to the development
      of novel therapeutic strategies for the treatment of Alzheimer's disease and
      other tauopathies. mRNA 3'-untranslated regions (3'-UTR) often regulate
      transcript stability or translation. Despite the centrality of the tau protein in
      Alzheimer's and other neurodegenerative diseases, the human tau 3'-UTR has been
      little studied. This report identifies regions of the tau 3'-UTR that influence
      expression and shows that microRNA (miR)-34a targets this 3'-UTR to lower
      expression, which is considered an important therapeutic goal. 

PMID- 24032462
TI  - Epilepsy on the horizon: Dublin forum focused on epilepsy care and research in
      Europe.

PMID- 24032463
TI  - Porous and robust lanthanide metal-organoboron frameworks as water tolerant Lewis
      acid catalysts.
AB  - Porous and robust 12-connected metal-organic frameworks (MOFs) were constructed
      by linking tetranuclear lanthanide (Ln) carbonate clusters with organoboron
      derived tricarboxylate bridging ligands. The high-connectivity Ln-MOFs feature
      remarkable thermal and hydrolytic stability and a large number of isolated Lewis
      acid B(III) and Ln(III) sites on the pore surfaces. The Nd-MOF assisted with
      sodium dodecylsulfate was found to be highly effective, recyclable, and reusable
      heterogeneous catalyst for the carbonyl allylation reaction, the Diels-Alder
      reaction, and the Strecker-type reaction in water. The transformations were
      cocatalyzed by Nd(III) and B(III) Lewis acids, with activities much higher than
      those of the individual organoboron and lanthanide counterparts and their
      mixture. This work highlights the potential of generating highly efficient water
      tolerant solid catalysts via heterogenization of different weak and/or mild Lewis
      acids in confined spaces of robust MOFs. 

PMID- 24032464
TI  - Would the indwelling internal ureteral stent influence renal function despite
      relief of benign ureteral obstruction?
AB  - OBJECTIVES: To assess the effect of internal ureteral stents (IUS) on renal
      function (RF) and to determine factors associated with the RF changes. METHODS:
      Between February 2009 and September 2012, 103 patients with bilateral or IUS in a
      solitary kidney were retrospectively analyzed. The estimated glomerular
      filtration rate (eGFR) was calculated using the Chronic Kidney Disease
      Epidemiology Collaboration Equation (CKD-EPI). It was calculated from serum
      creatinine after adequate relief of obstruction (baseline) and at last follow-up.
      Deterioration of eGFR was considered if the last eGFR declined by >20% from the
      baseline value. Predictors of RF changes were detected using univariate and
      multivariate binary logistic regression analyses. RESULTS: The mean patients' age
      was 54+/-14 years with males constituting 71.4% of the study population. During
      follow-up after IUS fixation, the median eGFR has declined from 50.6 mL/min/1.73
      m(2) at baseline to 25 mL/min/1.73 m(2) at time of last follow-up (p<0.0001).
      Fifty-two (50.5%) patients experienced decline in their RF by >20% of baseline
      value. On multivariate analysis, positive urine culture (odds ratio [OR]: 3;
      p=0.026), baseline eGFR <60 mL/min (OR: 3.6; p=0.011), and extraluminal
      obstruction (OR: 2.9; p=0.035) were independent predictors of RF deterioration.
      CONCLUSIONS: One half of patients with IUS lasting more than 3 months experienced
      RF deterioration during follow-up. This decline was significantly associated with
      positive urine cultures, presence of CKD, and extraluminal obstruction. All
      efforts should be exerted for active treatment of associated urinary tract
      infection and active follow-up of RF.

PMID- 24032465
TI  - Dopant-induced modification of active site structure and surface bonding mode for
      high-performance nanocatalysts: CO oxidation on capping-free (110)-oriented
      CeO2:Ln (Ln = La-Lu) nanowires.
AB  - Active center engineering at atomic level is a grand challenge for catalyst
      design and optimization in many industrial catalytic processes. Exploring new
      strategies to delicately tailor the structures of active centers and bonding
      modes of surface reactive intermediates for nanocatalysts is crucial to high
      efficiency nanocatalysis that bridges heterogeneous and homogeneous catalysis.
      Here we demonstrate a robust approach to tune the CO oxidation activity over CeO2
      nanowires (NWs) through the modulation of the local structure and surface state
      around Ln(Ce)' defect centers by doping other lanthanides (Ln), based on the
      continuous variation of the ionic radius of lanthanide dopants caused by the
      lanthanide contraction. Homogeneously doped (110)-oriented CeO2:Ln NWs with no
      residual capping agents were synthesized by controlling the redox chemistry of
      Ce(III)/Ce(IV) in a mild hydrothermal process. The CO oxidation reactivity over
      CeO2:Ln NWs was dependent on the Ln dopants, and the reactivity reached the
      maximum in turnover rates over Nd-doped samples. On the basis of the results
      obtained from combined experimentations and density functional theory
      simulations, the decisive factors of the modulation effect along the lanthanide
      dopant series were deduced as surface oxygen release capability and the bonding
      configuration of the surface adsorbed species (i.e., carbonates and bicarbonates)
      formed during catalytic process, which resulted in the existence of an optimal
      doping effect from the lanthanide with moderate ionic radius.

PMID- 24032466
TI  - Design, synthesis and biological screening of some pyridinylpyrazole and
      pyridinylisoxazole derivatives as potential anti-inflammatory, analgesic,
      antipyretic and antimicrobial agents.
AB  - A series of substituted pyridinylpyrazole (or isoxazole) derivatives were
      synthesized and evaluated for their anti-inflammatory (AI) activity using
      formalin-induced paw edema bioassays. Their inhibitory activities of
      cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) were also determined. The
      analgesic activity of the same compounds was evaluated using rat-tail withdrawal
      technique. Their antipyretic activity was also evaluated. The results revealed
      that compounds 4a,b, 6a, 8a, 14c and 15a exhibited significant AI and analgesic
      activities. Compounds 5a, 6a and 8a displayed good antipyretic activity.
      Compounds 14c and 15a showed good COX-2 inhibitory activity and weak inhibition
      of COX-1. Additionally, the most active compounds were shown to have a large
      safety margin (ALD50 >300-400 mg / Kg) and minimal ulcerogenic potentialities
      when administered orally at a dose of 300 mg/Kg. Docking studies for 14c and 15a
      with COX-2 showed good binding profile. Antimicrobial evaluation proved that most
      of the compounds exhibited distinctive activity against the gram negative
      bacteria, P. aeruginosa and E coli. 

PMID- 24032467
TI  - Detectable serum ethylene glycol levels after subcutaneous injection of
      antifreeze.

PMID- 24032468
TI  - The role of chest and abdominal computed tomography in assessing the severity of
      acute corrosive ingestion.
AB  - CONTEXT: Corrosive substance ingestion is a toxicological emergency with
      relatively high mortality requiring rational surgical decisions. OBJECTIVE:
      Evaluate the role of chest and abdominal computed tomography (CT) in assessing
      the severity of acute corrosive ingestion. METHODS: A retrospective study of
      adults admitted due to corrosive ingestion, who underwent gastrointestinal
      endoscopy and CT within 48 h of admission. Endoscopy findings were graded as 0,
      1, 2a, 2b, 3a, and 3b (Zargar's criteria), CT findings were graded as 0, 1, 2,
      and 3. For each patient endoscopy and CT grades were compared, and sensitivity
      and specificity for predicting mortality or emergency laparotomy were calculated.
      RESULTS: Twenty-three patients were included, aged 18-87 years; seven underwent
      emergency laparotomy, five died. Endoscopy grading was higher than CT grading in
      14 patients (66%). The sensitivities of endoscopy grades 2b and 3 to predict
      mortality and emergency laparotomy were 1 and 0.8, respectively; the
      specificities were 0.38 and 0.37, respectively. The sensitivities of CT grade 3
      to predict mortality and emergency laparotomy were 0.4 and 0.28, respectively;
      the specificities were 0.94 and 0.93, respectively. Three patients had pulmonary
      infiltrates on CT but not on chest X-ray. DISCUSSION. CT tends to underestimate
      the severity of corrosive ingestion compared with endoscopy. It has lower
      sensitivity and higher specificity than endoscopy in predicting major outcome. CT
      can provide important information on lung injury, and when endoscopy cannot be
      completed. CONCLUSION: CT should not be the only basis for surgical decisions
      during the initial phase of acute corrosive ingestions.

PMID- 24032469
TI  - Residue analyses and exposure assessment of the Irish population to nitrofuran
      metabolites from different food commodities in 2009-2010.
AB  - An exposure assessment to nitrofuran residues was performed for three human
      populations (adults, teenagers and children), based on residue analyses of foods
      of animal origin (liver, honey, eggs and aquaculture) covering the 2-year period
      2009-2010. The occurrence of nitrofuran metabolites in food on the Irish market
      was determined for the selected period using the data from Ireland's National
      Food Residue Database (NFRD) and from results obtained from the analysis of
      retail samples (aquaculture and honey). Laboratory analyses of residues were
      performed by methods validated in accordance with Commission Decision 2002/657/EC
      regarding performance of the analytical method and interpretation of results.
      Semicarbazide (SEM) was the contaminant most frequently identified and its
      content ranged from 0.09 to 1.27 MUg kg(-1). SEM is currently used as a marker of
      nitrofuran abuse, but it may also occur from other sources. The presence of
      nitrofuran metabolite 3-amino-2-oxazolidinone (AOZ) was detected in two
      aquaculture samples (prawns) at 1.63 and 1.14 MUg kg(-1), but such a low number
      of positive cases did not present sufficient data for a full AOZ exposure
      assessment. Therefore, the evaluation of exposure was focused on SEM-containing
      food groups only. Exposure assessments were completed using a probabilistic
      approach that generated 10 iterations. The results of both the upper- and lower
      bound exposure assessments demonstrate that SEM exposure for Irish adults,
      teenagers and children from selected food commodities are well below EFSA
      estimated safe levels. 

PMID- 24032471
TI  - Three-Dimensional Nonlinear Contact Finite Element Analysis of Mandibular All-on
      4 Design.
AB  - The All-on-4 design was used successfully for restoring edentulous mandible. This
      design avoids anatomic cripples such as inferior alveolar nerve by tilting
      posterior implants. Moreover, tilting posterior implants of All-on-4 design had a
      mechanical preference than the conventional design. On the other hand, the
      anterior implants are parallel at the lateral incisor region. Several researches
      showed favorable results for tilting posterior implants. However, research did
      not study the influence of the anterior implant position or orientation on the
      mechanical aspects of this design. This study analyzes the influence of varying
      anterior implant position and orientation of the All-on-4 design using nonlinear
      contact 3D finite-element analysis. Three copied 3-dimensional models of the All
      on-4 design were classified according to anterior implant position and
      orientation. The frictional contact between fixtures and bone was the contact
      type in this finite element analysis. Finally, von Mises stress and strain at
      implant and bone levels were recorded and analyzed using finite element software.
      Stress concentrations were detected mainly around the posterior implant at the
      loaded side. Values of the maximum equivalent stress and strain were around
      tilted implants of design III followed by design II, then design I. Changing the
      position or orientation of the anterior implants in All-on-4 design influences
      stress-strain distribution of the whole design. 

PMID- 24032470
TI  - Corticosteroids inhibit sphingosine 1-phosphate-induced interleukin-6 secretion
      from human airway smooth muscle via mitogen-activated protein kinase phosphatase
      1-mediated repression of mitogen and stress-activated protein kinase 1.
AB  - Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that plays an important
      proinflammatory role in asthmatic airways. Corticosteroids are first-line
      antiinflammatories in asthma; however, their repressive effects on S1P-induced
      cytokine secretion have not been investigated. To address this, our in vitro
      study reveals the molecular mechanisms by which corticosteroids inhibit S1P
      induced IL-6 expression in the pivotal immunomodulatory cell type, airway smooth
      muscle (ASM). We first uncover the cellular signaling pathways responsible: S1P
      activates a cyclic adenosine monophosphate/cAMP response-element-binding protein
      (CREB)/CRE-dependent pathway to induce IL-6 transcription, concomitant with
      stimulation of the mitogen-activated protein kinase (MAPK) superfamily and
      downstream mitogen and stress-activated protein kinase 1 (MSK1) and histone H3
      phosphorylation. In this way, S1P stimulates parallel signaling pathways to
      induce IL-6 secretion via CRE-driven transcription of the IL-6 gene promoter in a
      relaxed chromatin environment achieved through histone H3 phosphorylation.
      Second, we investigated how corticosteroids mediate their repressive effects. The
      corticosteroid dexamethasone inhibits S1P-induced IL-6 protein secretion and mRNA
      expression, but CREB/CRE transrepression, inhibition of IL-6 mRNA stability, or
      subcellular relocation of MSK1 were not responsible for the repressive effects of
      dexamethasone. Rather, we show that dexamethasone rapidly induces up-regulation
      of the MAPK deactivator MAPK phosphatase 1 (MKP-1) and that MKP-1 blocks the MAPK
      driven activation of MSK1 and phosphorylation of histone H3. This was confirmed
      by treatment with triptolide, an inhibitor of MKP-1 up-regulation, where
      repressive effects of corticosteroids were reversed. Our study reveals the
      molecular mechanism underlying the antiinflammatory capacity of corticosteroids
      to repress proinflammatory functions induced by the potent bioactive sphingolipid
      S1P in the lung. 

PMID- 24032472
TI  - Effects of marine overwash for atoll aquifers: environmental and human factors.
AB  - Inundation of atoll islands by marine overwash is a serious threat to fresh
      groundwater, which can be a critical emergency water resource after artificial
      storage or other water resource infrastructure has been exhausted or destroyed.
      In contrast to drought, which slowly exhausts water supplies and often can be
      forecasted in time, overwash can occur with little warning and can ruin both rain
      catchment storage and groundwater reserves. In this study, a SUTRA-based model is
      applied to estimate how groundwater contamination by overwash and subsequent
      recovery of fresh groundwater are influenced by geologic factors (aquifer
      hydraulic conductivity, dispersivity, and the presence or absence of a reef flat
      plate), the seasonal timing of the event (wet vs. dry), and the presence of hand
      dug wells that penetrate the reef flat plate. Actual tidal and rainfall data from
      regions in the western Pacific are applied to simulated 30-month recovery periods
      for hypothetical islands with properties and conditions characteristic of the
      western Pacific. For all scenarios, results indicate that 12 to 16 months are
      required to achieve 60% recovery of fresh groundwater. However, the time required
      to restore useful quantities of groundwater to acceptable salt concentration at
      depths typical of hand-dug wells is only 3 to 6 months. Of particular interest is
      the influence of the reef flat plate, which acts as a barrier to infiltrating
      seawater, thus preserving a pocket of confined freshwater during an overwash
      event and the recovery, which could probably be utilized if the necessary tools
      and equipment are on hand. 

PMID- 24032473
TI  - Inoculation of selenium hyperaccumulator Stanleya pinnata and related non
      accumulator Stanleya elata with hyperaccumulator rhizosphere fungi--investigation
      of effects on Se accumulation and speciation.
AB  - Little is known about how fungi affect elemental accumulation in
      hyperaccumulators (HAs). Here, two rhizosphere fungi from selenium (Se) HA
      Stanleya pinnata, Alternaria seleniiphila (A1) and Aspergillus leporis (AS117),
      were used to inoculate S. pinnata and related non-HA Stanleya elata. Growth and
      Se and sulfur (S) accumulation were analyzed. Furthermore, X-ray microprobe
      analysis was used to investigate elemental distribution and speciation. Growth of
      S. pinnata was not affected by inoculation or by Se. Stanleya elata growth was
      negatively affected by AS117 and by Se, but combination of both did not reduce
      growth. Selenium translocation was reduced in inoculated S. pinnata, and
      inoculation reduced S translocation in both species. Root Se distribution and
      speciation were not affected by inoculation in either species; both species
      accumulated mainly (90%) organic Se. Sulfur, in contrast, was present equally in
      organic and inorganic forms in S. pinnata roots. Thus, these rhizosphere fungi
      can affect growth and Se and/or S accumulation, depending on host species. They
      generally enhanced root accumulation and reduced translocation. These effects
      cannot be attributed to altered plant Se speciation but may involve altered
      rhizosphere speciation, as these fungi are known to produce elemental Se. Reduced
      Se translocation may be useful in applications where toxicity to herbivores and
      movement of Se into the food chain is a concern. The finding that fungal
      inoculation can enhance root Se accumulation may be useful in Se biofortification
      or phytoremediation using root crop species. 

PMID- 24032474
TI  - FRET-based biofriendly apo-GO(x)-modified gold nanoprobe for specific and
      sensitive glucose sensing and cellular imaging.
AB  - In this paper, we have developed a biofriendly and high sensitive apo-GOx
      (inactive form of glucose oxidase)-modified gold nanoprobe for quantitative
      analysis of glucose and imaging of glucose consumption in living cells. This
      detection system is based on fluorescence resonance energy transfer between apo
      GOx modified AuNPs (Au nanoparticles) and dextran-FITC (dextran labeled with
      fluorescein isothiocyanate). Once glucose is present, quenched fluorescence of
      FITC recovers due to the higher affinity of apo-GOx for glucose over dextran. The
      nanoprobe shows excellent selectivity toward glucose over other monosaccharides
      and most biological species present in living cells. A detection limit as low as
      5 nM demonstrates the high sensitivity of the nanoprobe. Introduction of apo-GOx,
      instead of GOx, can avoid the consumption of O2 and production of H2O2 during the
      interaction with glucose, which may exert effects on normal physiological events
      in living cells and even lead to cellular damage. Due to the low toxicity of this
      detection system and reliable cellular uptake ability of AuNPs, imaging of
      intracellular glucose consumption was successfully realized in cancer cells. 

PMID- 24032476
TI  - Synthesis and characterization of new derivatives of alginic acid and evaluation
      of their iron(III)-crosslinked beads as potential controlled release matrices.
AB  - CONTEXT: The excellent gelling and safety profiles of alginic acid combined,
      however, with drawbacks of its ionotropically crosslinked beads (i.e. their quick
      release of loaded drugs) prompted us to chemically modify alginic acid.
      OBJECTIVE: Alginic acid was chemically conjugated with four amines of varying
      hydrophilic-hydrophobic properties (i.e. tris(hydroxymethyl)methyl-, allyl-,
      benzyl- or pentyl-amines) in an attempt to enhance the drug release profiles from
      respective metal crosslinked beads. MATERIALS AND METHODS: Chemical conjugation
      procedures were performed using dicyclohexylcarbodiimide as a coupling agent and
      the resulting new derivatives were characterized using proton nuclear magnetic
      resonance ((1)H NMR), infrared (IR) spectroscopy and differential scanning
      calorimetry (DSC). These modified polymers were used to prepare iron (III)
      crosslinked beads loaded with folic acid as model drug, which were tested in
      vitro to assess their folic acid release profiles. RESULTS AND DISCUSSION:
      Interestingly, the resulting beads accessed enteric release kinetics, with
      tris(hydroxymethyl)methyl-amide alginic conjugate producing most pronounced
      enteric profile. CONCLUSION: The results suggest the possibility of achieving
      controlled drug release from alginate-based beads via facile chemical
      modification of alginic acid.

PMID- 24032475
TI  - Disease-modifying therapy in multiple sclerosis and chronic inflammatory
      demyelinating polyradiculoneuropathy: common and divergent current and future
      strategies.
AB  - Multiple sclerosis (MS) and chronic inflammatory demyelinating
      polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating
      disorders of the central and peripheral nervous system. Although both disorders
      share some fundamental pathogenic elements, treatments do not provide uniform
      effects across both disorders. We aim at providing an overview of current and
      future disease-modifying strategies in these disorders to demonstrate
      communalities and distinctions. Intravenous immunoglobulins (IVIG) have
      demonstrated short- and long-term beneficial effects in CIDP but are not
      effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are
      orally administered immunomodulatory drugs that are already approved or likely to
      be approved in the near future for the basic therapy of patients with relapsing
      remitting MS (RRMS) due to positive results in Phase III clinical trials.
      However, clinical trials with these drugs in CIDP have not (yet) been initiated.
      Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to
      evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab,
      ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of
      clinical development for their use in RRMS patients. Attempts to study the safety
      and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e.
      rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way.
      We provide an overview of the mechanism of action and clinical data available on
      disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding
      of the relative effects of therapies in these two disorders may aid rational
      treatment selection and the development of innovative treatment approaches in the
      future. 

PMID- 24032478
TI  - A(2A) adenosine receptors and Parkinson's disease severity.
AB  - OBJECTIVES: In the last decade, increasing evidence suggests a key role of
      adenosine in Parkinson's disease (PD) and A2A adenosine receptors (A2A ARs) as an
      important pharmacological target in PD. An overexpression of A2A ARs has been
      found in putamen and in peripheral blood cells of PD patients. The primary aim of
      this study was to verify whether the alterations in A2A ARs in lymphocytes of PD
      subjects correlate with disease severity. MATERIAL AND METHODS: A consecutive
      sample of PD patients was enrolled. A clinical examination and a face-to-face
      interview were carried out. A2A ARs were investigated to verify the affinity and
      receptor density in lymphocyte membranes. The data were compared with those found
      in healthy controls. Moreover, the correlation between A2A AR density and
      affinity and clinical variables was evaluated in PD patients. RESULTS: In human
      lymphocyte membranes from PD patients, an increase in A2A AR density and a
      decrease in A2A AR affinity were found if compared with healthy subjects. A
      statistically significant correlation between the A2A AR density or affinity and
      specific clinical parameters as motor and cognitive impairment was detected.
      Patients with higher A2A AR density and lower affinity were more likely to
      exhibit motor complications. CONCLUSIONS: Parkinson's disease patients show an
      A2A AR upregulation in lymphocyte membranes if compared with healthy subjects.
      The correlation found between A2A AR density or affinity and clinical parameters
      highlights the central role of A2A AR modulation in the pharmacological treatment
      for PD and could suggest the putative role of A2A AR as a candidate biomarker of
      PD severity.

PMID- 24032477
TI  - Identification and characterization of second-generation invader locked nucleic
      acids (LNAs) for mixed-sequence recognition of double-stranded DNA.
AB  - The development of synthetic agents that recognize double-stranded DNA (dsDNA) is
      a long-standing goal that is inspired by the promise for tools that detect,
      regulate, and modify genes. Progress has been made with triplex-forming
      oligonucleotides, peptide nucleic acids, and polyamides, but substantial efforts
      are currently devoted to the development of alternative strategies that overcome
      the limitations observed with the classic approaches. In 2005, we introduced
      Invader locked nucleic acids (LNAs), i.e., double-stranded probes that are
      activated for mixed-sequence recognition of dsDNA through modification with "+1
      interstrand zippers" of 2'-N-(pyren-1-yl)methyl-2'-amino-alpha-l-LNA monomers.
      Despite promising preliminary results, progress has been slow because of the
      synthetic complexity of the building blocks. Here we describe a study that led to
      the identification of two simpler classes of Invader monomers. We compare the
      thermal denaturation characteristics of double-stranded probes featuring
      different interstrand zippers of pyrene-functionalized monomers based on 2'-amino
      alpha-l-LNA, 2'-N-methyl-2'-amino-DNA, and RNA scaffolds. Insights from
      fluorescence spectroscopy, molecular modeling, and NMR spectroscopy are used to
      elucidate the structural factors that govern probe activation. We demonstrate
      that probes with +1 zippers of 2'-O-(pyren-1-yl)methyl-RNA or 2'-N-methyl-2'-N
      (pyren-1-yl)methyl-2'-amino-DNA monomers recognize DNA hairpins with similar
      efficiency as original Invader LNAs. Access to synthetically simple monomers will
      accelerate the use of Invader-mediated dsDNA recognition for applications in
      molecular biology and nucleic acid diagnostics. 

PMID- 24032479
TI  - Topiramate as an add-on antiepileptic drug in treating refractory canine
      idiopathic epilepsy.
AB  - OBJECTIVES: To evaluate the efficacy and safety of topiramate as an add-on
      therapy in dogs with refractory idiopathic epilepsy. METHOD: Prospective, open
      label, non-comparative clinical trial of topiramate in dogs with idiopathic
      epilepsy and poor seizure control despite therapeutic serum concentrations of
      phenobarbital and potassium bromide. The efficacy of topiramate was evaluated by
      comparing seizure and seizure day frequencies during a retrospective 2-month
      period with a prospective short-term follow-up of 6 months. An additional long
      term follow-up period ranging from 3 to 9 months was conducted on dogs that
      responded to topiramate therapy during the short-term follow-up. RESULTS: Ten
      dogs were included. Five (50%) responded to topiramate therapy during the short
      term follow-up showing a significant (P=0.04) decrease of 66% in seizure
      frequency. Three of the five dogs remained responders during the long-term follow
      up. Weight loss, sedation and ataxia were the most common adverse effects of
      topiramate therapy, but in dogs with moderate sedation or ataxia, signs subsided
      in a few weeks to few months to mild sedation or ataxia. CLINICAL SIGNIFICANCE:
      Topiramate may be effective as an add-on medication in treating canine idiopathic
      epilepsy. Apart from sedation and ataxia reported in some of the dogs, topiramate
      was well-tolerated.

PMID- 24032480
TI  - Short- and long-term outcome of linear morphoea in children.
AB  - BACKGROUND: Linear morphoea (LM) is a rare fibrosing disorder of the limbs or the
      face that may cause functional disability and severe aesthetic sequelae. Despite
      a wide range of therapeutics reported for LM, there is currently a lack of
      consensus on the optimal therapy. Little is known about the long-term outcome of
      this disease. OBJECTIVES: To describe the short- and long-term outcome of a large
      series of patients with LM acquired in childhood. METHODS: A retrospective chart
      review of 52 paediatric patients with LM seen in our centre during a 20-year span
      (1990-2010) and a telephone survey in 2011 to assess the long-term outcome of
      these patients. RESULTS: Limbs were affected twice as often as the face, with a
      higher proportion of female patients. Stabilization was obtained after a mean
      disease duration of 5.4 years. Patients sometimes experienced long stretches of
      disease quiescence followed by reactivation; 31% of patients reported active
      disease after 10 years. All but one patient had aesthetic sequelae, and 38% had
      functional limitations. The effectiveness of methotrexate and systemic
      corticosteroids was apparent in the short term. CONCLUSIONS: LM needs prolonged
      monitoring as the disease can have very long periods of quiescence followed by
      reactivation. The combination of methotrexate and systemic corticosteroids was
      effective in the early stages of the disease but did not seem to prevent long
      standing active disease or relapse in the long term.

PMID- 24032481
TI  - Proteome analysis of plastids from developing seeds of Jatropha curcas L.
AB  - In this study, we performed a proteomic analysis of plastids isolated from the
      endosperm of developing Jatropha curcas seeds that were in the initial stage of
      deposition of protein and lipid reserves. Proteins extracted from the plastids
      were digested with trypsin, and the peptides were applied to an EASY-nano LC
      system coupled inline to an ESI-LTQ-Orbitrap Velos mass spectrometer, and this
      led to the identification of 1103 proteins representing 804 protein groups, of
      which 923 proteins were considered as true identifications, and this considerably
      expands the repertoire of J. curcas proteins identified so far. Of the identified
      proteins, only five are encoded in the plastid genome, and none of them are
      involved in photosynthesis, evidentiating the nonphotosynthetic nature of the
      isolated plastids. Homologues for 824 out of 923 identified proteins were present
      in PPDB, SUBA, or PlProt databases while homologues for 13 proteins were not
      found in any of the three plastid proteins databases but were marked as
      plastidial by at least one of the three prediction programs used. Functional
      classification showed that proteins belonging to amino acids metabolism comprise
      the main functional class, followed by carbohydrate, energy, and lipid
      metabolisms. The small and large subunits of Rubisco were identified, and their
      presence in the plastids is considered to be an adaptive feature counterbalancing
      for the loss of one-third of the carbon as CO2 as a result of the conversion of
      carbohydrate to oil through glycolysis. While several enzymes involved in the
      biosynthesis of several precursors of diterpenoids were identified, we were
      unable to identify any terpene synthase/cyclase, which suggests that the plastids
      isolated from the endosperm of developing seeds do not synthesize phorbol esters.
      In conclusion, our study provides insights into the major biosynthetic pathways
      and certain unique features of the plastids from the endosperm of developing
      seeds at the whole proteome level. 

PMID- 24032482
TI  - Triplet state formation in photoexcited slip-stacked perylene-3,4:9,10
      bis(dicarboximide) dimers on a xanthene scaffold.
AB  - Two covalent perylene-3,4:9,10-bis(dicarboximide) (PDI) dimers in which the PDI
      molecules are attached to a xanthene (Xan) scaffold in which the long axes of the
      two pi-pi stacked PDI molecules are slipped by 4.3 and 7.9 A were prepared. These
      dimers are designed to mimic J-aggregates and provide insights into the
      photophysics of triplet state formation in PDI aggregates that target organic
      electronics. Using ultrafast transient absorption and stimulated Raman
      spectroscopy, the mechanism of (3)*PDI formation was found to depend strongly on
      a competition between the rate of Xan(*+)-PDI(*-) formation involving the spacer
      group and the rate of excimer-like state formation. Which mechanism is favored
      depends on the degree of electronic coupling between the two PDI molecules and/or
      solvent polarity. Singlet exciton fission to produce (3)*PDI does not compete
      kinetically with these processes. The excimer-like state decays relatively slowly
      with tau = 28 ns to produce (3)*PDI, while charge recombination of Xan(*+)-PDI(*
      ) yields (3)*PDI more than an order of magnitude faster. The perpendicular
      orientation between the pi orbitals of PDI and the Xan bridge provides a large
      enough orbital angular momentum change to greatly increase the intersystem
      crossing rate via Xan(*+)-PDI(*-) -> (3)*PDI charge recombination. These results
      highlight the importance of understanding inter-chromophore electronic coupling
      in a wide range of geometries as well as the active role that molecular spacers
      can play in the photophysics of covalent models for self-assembled chromophore
      aggregates. 

PMID- 24032483
TI  - Targeted resequencing for analysis of clonal composition of recurrent gene
      mutations in chronic lymphocytic leukaemia.
AB  - Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic
      leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to
      determine the genetic profile, intratumoural heterogeneity, and clonal structure
      of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were most frequently
      mutated (16.3%, 16.9%, 10.7%). We found evidence for subclonal mutations in 67.5%
      of CLL cases with mutations of cancer consensus genes. We observed selection of
      subclones and found initial evidence for convergent mutations in CLL. Our data
      suggest that assessment of (sub)clonal structure may need to be integrated into
      analysis of the mutational profile in CLL.

PMID- 24032484
TI  - Robust superhydrophobic/superoleophilic sponge for effective continuous
      absorption and expulsion of oil pollutants from water.
AB  - With the growth of oil production and transportation, there is greater potential
      for accidental oil spills. Here we fabricated a robust superhydrophobic and
      superoleophilic carbon nanotube/poly(dimethylsiloxane)-coated polyurethane sponge
      for the continuous absorption and expulsion of oils and organic solvents from
      water surfaces. When applied in conjunction with a vacuum system, this sponge
      could separate great amounts of oils-up to 35000 times its own weight-from water
      in a one-step process and could also separate surfactant-free water-in-oil
      emulsions with high efficiency (oil purity: >99.97 wt %), making it a promising
      candidate material for use in oil-spill cleanups. 

PMID- 24032485
TI  - Understanding the effect of secondary structure on molecular interactions of poly
      L-lysine with different substrates by SFA.
AB  - Nonspecific adsorption of proteins on biomaterial surfaces challenges the
      widespread application of engineered materials, and understanding the impact of
      secondary structure of proteins and peptides on their adsorption process is of
      both fundamental and practical importance in bioengineering. In this work, poly-L
      lysine (PLL)-based alpha-helices and beta-sheets were chosen as a model system to
      investigate the effect of secondary structure on peptide interactions with
      substrates of various surface chemistries. Circular dichroism (CD) was used to
      confirm the presence of both alpha-helix and beta-sheet structured PLL in aqueous
      solutions and upon adsorption to quartz, where these secondary structures seemed
      to be preserved. Atomic force microscopy (AFM) imaging showed different surface
      patterns for adsorbed alpha-helix and beta-sheet PLL. Interactions between PLL of
      different secondary structures and various substrates (i.e., PLL, Au, mica, and
      poly(ethylene glycol) (PEG)) were directly measured using a surface forces
      apparatus (SFA). It was found that beta-sheet PLL films showed higher adsorbed
      layer thicknesses in general. Adhesion energies of beta-sheet versus Au and beta
      sheet versus beta-sheet were considerably higher than that of alpha-helix versus
      Au and alpha-helix versus alpha-helix systems, respectively. Au and beta-sheet
      PLL interactions seemed to be more dependent on the salt concentration than that
      of alpha-helix, while the presence of a grafted PEG layer greatly diminished any
      attraction with either PLL structure. The molecular interaction mechanism of
      peptide in different secondary structures is discussed in terms of Derjaguin
      Landau-Verwey-Overbeek (DLVO) theory, Alexander-de Gennes (AdG) steric model and
      hydrogen bonding, which provides important insight into the fundamental
      understanding of the interaction mechanism between proteins and biomaterials.

PMID- 24032486
TI  - A beta-boronopeptide bundle of known structure as a vehicle for polyol
      recognition.
AB  - Despite significant progress in the design of receptors and sensors for simple
      polyols and monosaccharides, few synthetic receptors discriminate among multiple
      saccharide units simultaneously, especially under physiological conditions.
      Described here is the three-dimensional structure of a supramolecular complex-a
      beta-peptide bundle-designed for the potential to interact simultaneously with as
      many as eight discrete monosaccharide units. The preliminary evaluation of this
      construct as a vehicle for polyol binding is also presented. 

PMID- 24032487
TI  - Empiric validation of simulation models for estimating glucose meter performance
      criteria for moderate levels of glycemic control.
AB  - BACKGROUND: We used simulation modeling to relate glucose meter performance
      criteria to insulin dosing errors for patients on a moderate glycemic control
      protocol (glucose target, 110-150 mg/dL) and empirically validated assumptions
      from simulation models using observed glucose meter and laboratory glucose values
      obtained nearly simultaneously. SUBJECTS AND METHODS: The 25,948 glucose values
      from 1,513 patients on a moderate glycemic control protocol were used to
      represent the expected distribution of glucose values in this patient population.
      Simulation models were used to relate glucose meter analytical performance to
      insulin dosing errors assuming 10%, 15%, or 20% total allowable error (TEa). In
      addition, 4,017 paired glucose meter and serum laboratory glucose measurements
      drawn within 5 min of each other were used to generate an empiric dataset to
      validate simulation model assumptions relating glucose meter performance to
      insulin dosing errors. RESULTS: Large (three or more category) insulin dosing
      errors are predicted to occur only under the 20% TEa condition. Two category
      insulin dosing errors were common (6-20% of all insulin dosing decisions) when
      20% TEa was assumed, but frequency decreased to only 0.2% of dosing decisions
      when 10% TEa was modeled. When insulin dosing error rates were measured
      empirically by comparing paired glucose meter and laboratory glucose values,
      insulin dosing error rates were very similar to those predicted for the 20% TEa
      condition. CONCLUSIONS: Both simulation models and empiric data demonstrate that
      glucose meters that perform at >=20% TEa allow large insulin dosing errors during
      a moderate glycemic control protocol.

PMID- 24032488
TI  - Medical students in psychiatry.

PMID- 24032489
TI  - Research into recruitment: critical gaps in the literature.
AB  - The aim of this paper is to systematically review the literature available
      internationally on recruitment into psychiatry. A 5-stage search strategy was
      followed to identify all relevant studies published between 1999-2012. These were
      then critically appraised using a standardized tool, and the results summarized.
      A total of 128 studies were identified. Surveys were the most common design
      (40%), and 76% of studies used medical students as subjects; 36% of the studies
      were from the USA, followed by 25% from the UK. There were no studies found from
      South America. There is a need for more research into other potential applicant
      groups before medical school, and for research carried out in Africa, Asia and
      South America.

PMID- 24032490
TI  - What attracts medical students towards psychiatry? A review of factors before and
      during medical school.
AB  - Potential psychiatrists decide on their careers before, during or after medical
      school. This article summarises the literature focusing on the first two groups.
      Pre-medical school factors associated with choosing psychiatry include gender,
      academic aptitude, ethnicity and migration, exposure to mental illness, economic
      considerations and medical school route and selection. Factors involved in
      influencing career choice at medical school level include attitudes towards
      psychiatry, teaching methods, quality and length of clinical exposure, electives
      and enrichment activities, and personality factors. Considering these factors may
      improve recruitment to psychiatry and address shortages in the speciality.

PMID- 24032491
TI  - Undergraduate medical students' attitudes towards psychiatry: an international
      cross-sectional survey between India and Japan.
AB  - Undergraduate psychiatric education has an important role in developing
      psychiatric knowledge, decreasing stigma towards mental illness, and promoting
      psychiatry as a career choice. The attitudes and beliefs of medical students
      towards psychiatry have not been well understood, especially in non-western
      countries. To clarify this aspect, we have conducted a cross-sectional study
      between India and Japan. This study, conducted at two centres, one each in India
      and Japan, used a semi-structured questionnaire to evaluate the attitudes and
      beliefs of third-year medical students towards mental illness and psychiatry;
      such as emotions experienced dealing with psychiatric patients, aetiology and
      treatment of psychiatric disorders, and psychiatry as a career choice. A total of
      79 medical students from India and 77 from Japan participated in the present
      study. Significant differences were observed in the emotions experienced by the
      medical students while dealing with psychiatric patients. Most medical students
      (> 90%) from both study sites favoured psychiatrists for treatment of psychiatric
      illness. Psychiatry as a carrier choice was significantly related to the
      nationality of the medical students. The findings of the current study provide
      insight in to the attitudes of third-year medical students from India and Japan
      towards psychiatric patients.

PMID- 24032492
TI  - Recruiting medical students into psychiatry in lower income countries.
AB  - There is a serious shortage of psychiatrists and poor recruitment of new
      psychiatry trainees worldwide. Low and middle income countries suffer
      disproportionately on many accounts. A negative attitude towards psychiatry is
      thought to contribute to poor recruitment of psychiatry trainees. Previous
      reviews have focused on the attitudes of medical students in high income
      countries, but factors relevant to attitude and recruitment may be different in
      lower income countries. Here we review studies of medical students' attitudes
      towards psychiatry from low and lower-middle income countries, summarize key
      themes which negatively influence attitudes, and suggest strategies for
      overcoming them. Major themes include stigma, perceived status of psychiatry,
      lack of psychiatric trainers, local cultural beliefs, poor working conditions,
      and quality of patient care.

PMID- 24032493
TI  - Motivations of medical students towards psychiatry: a perspective from Turkey.
AB  - Recruitment in psychiatry has been an ongoing challenge worldwide; Turkey is no
      exception. In this article we have reviewed the issue from multiple aspects.
      Negative opinions on psychiatry among medical students have been associated with
      various matters, such as problems with scientific soundness, stigma, prestige and
      financial incentives. It has been reported that these negative opinions could be
      reversed by clinical exposure, improved knowledge base and increased affiliation
      with the field. Unfortunately, reversed attitudes do not have permanency.
      Considering that there has not been any study focusing on recruitment problems in
      Turkey, we attempted to provide a perspective by reporting the results of our
      study conducted with Turkish medical students. Attractive qualities of psychiatry
      were of particular interest. We found that brain research, neuroscience,
      philosophy, psychotherapy and academics are main areas of interest in psychiatry.
      We attempt to discuss our findings in view of current literature while noting
      current setbacks of psychiatry residency training in Turkey. We conclude that
      there exists a great need for working strategies in order to improve recruitment
      in psychiatry, addressing the stigma and correcting false beliefs such as
      treatment inefficacy or compromised scientific solidity.

PMID- 24032494
TI  - Factors that influence the choice of psychiatry as a career by medical students
      at the School of Medicine, College of Health Sciences, University of Nairobi.
AB  - The aim of this paper is to assess the particular factors facilitating and those
      hampering the choice of psychiatry as a career by medical students at the
      University of Nairobi in a cross-sectional population study of medical students
      at the University of Nairobi, College of Health Sciences, School of Medicine
      using self-administered questionnaires. A total of 31 students (13%) said they
      would like to be psychiatrists while 44 (18%) were neutral and 170 (69%) did not
      want to become psychiatrists. The factors that made psychiatry interesting for
      the students included the view that the problems presented by psychiatric
      patients were often particularly interesting and challenging and the fact that
      mental illness presented the field of medicine with one of the greatest
      challenges. Discouraging factors articulated by the students included views that
      psychiatry was a vague and speculative speciality, psychiatry was not an
      important part of the curriculum in medical schools, and psychiatric patients
      tend to make more emotional demands on their doctors than other patients. There
      was a negative view of psychiatric patients who most of the students thought were
      strange, dangerous and incurable, although they were curious to know more about
      them. Most of the negative influence in psychiatry is due to the misconceptions
      that students have about its prestige and scope, the rewards it offers in terms
      of job satisfaction and opportunities and the negative views towards psychiatric
      patients. Integration of psychiatry into the curriculum may address these
      misunderstandings.

PMID- 24032495
TI  - Challenges for psychiatric recruitment and training in Chile.
AB  - This paper aims to describe the current challenges to recruitment of
      psychiatrists in Chile, and investigate factors related to interest in psychiatry
      from medical students of the Chilean Biobio Region. An online survey was
      completed by 39 medical students currently performing the internship. This survey
      included questions regarding socio-demographic aspects, probability of choosing a
      medical speciality, influencing factors on the choice of the medical speciality,
      and personal features. Students were separated in two groups for the analysis
      based on their likelihood of choosing psychiatry as a career. A total of 35.9% of
      the respondents showed some degree of interest in psychiatry. Factors considered
      important by the respondents were academic opportunities, training vacancies, and
      balance between job and personal life. The low participation in the study does
      not allow the extrapolation of data to the national situation, and may represent
      response bias to those already interested in psychiatry as a career. However,
      Chile has an average psychiatrist rate per number of inhabitants for the region,
      but an uneven distribution of this resource. National policies must be focused on
      this issue in order to reduce the gap in mental healthcare.

PMID- 24032496
TI  - Psychiatric specialization as an option for medical students in the Indian
      context.
AB  - There is a shortage of psychiatrists in India and psychiatry as a subject of
      specialization is not a preferred option among medical undergraduates. There is
      inadequate exposure to psychiatry during the medical undergraduate training in
      India which might contribute towards it. There are attempts to overcome the
      negative attitudes towards psychiatry and mental illness among medical
      undergraduates by changes in the curriculum. In this paper we attempt to review
      studies on attitudes of undergraduate students towards psychiatry and compare the
      results with findings from our own survey done as a part of International Study
      of Student Career Choice in Psychiatry (ISoSCCiP) project.

PMID- 24032497
TI  - Exploring the ideas and expectations of German medical students towards career
      choices and the speciality of psychiatry.
AB  - The aim of this study was to explore the ideas and expectations of medical
      students toward their career choices and the speciality of psychiatry. A total of
      323 students of the Hannover Medical School filled in a questionnaire about their
      career choices, preferred medical specialization, factors of influence on career
      choices and attitude towards psychiatry. The three most important factors of
      influence appeared to be: (1) work-life balance, (2) flexible working hours, (3)
      career prospects. Although expectations towards the professional life of
      psychiatrists were quite positive among the students, there was only a small
      number of students (n = 53 of 318 respondents, 17%) interested in specializing in
      psychiatry. Important reasons for choosing psychiatry included personal
      experience with somatic or mental health issues and practical experience in
      psychiatry. Most of the students experienced clinical exposure to psychiatry but
      at a much later period in the curriculum. For a career choice of psychiatry as a
      speciality it seems to be important to start psychiatric education in medical
      school early. The positive aspects of the professional life in psychiatry, such
      as flexible working hours, career prospects and good work-life balance should be
      more emphasized.

PMID- 24032498
TI  - Challenges for trainees in psychiatry and early career psychiatrists.
AB  - Psychiatry as a discipline will undergo major changes in the coming years.
      Although changes can be particularly stimulating and challenging from an
      intellectual, scientific and social viewpoint, the new generations of
      psychiatrists must be prepared to face these changes and deal with them
      appropriately. Paradigms which have represented the foundations of psychiatry in
      the last century now need a major revision. In particular, both trainees in
      psychiatry and early career psychiatrists need to (1) (re)discover
      psychopathology, (2) improve mental healthcare through integrated treatments, (3)
      identify and treat new syndromes, (4) promote an image of psychiatry with
      patients at the heart of care and as advocates for each other by fighting stigma
      and promoting the recruitment in psychiatry by medical students. These can be
      achieved by increasing involvement in institutions and organizations to influence
      the agenda. In this paper the possible contribution of trainees and early career
      psychiatrists is discussed and recommendations are made in order to set a new
      agenda for early career psychiatrists who will still be practising 2-3 decades
      from now.

PMID- 24032499
TI  - Student career choice in psychiatry: findings from 18 UK medical schools.
AB  - Psychiatry recruitment continues to be a problem in the UK and large-scale
      studies are required to understand the factors surrounding this. A quantitative,
      cross-sectional online survey, incorporating demographics, career choices,
      teaching exposure, attitudes to psychiatry and personality factors, was
      administered to final-year UK medical students. A total of 484 students from 18
      medical schools responded (66% women). Sixteen (16%) had chosen psychiatry at
      medical school entry. By final year, 15 respondents (3%) had decided to pursue a
      career in psychiatry, while another 78 (17%) were seriously considering it. There
      was little difference in the quality ratings of lectures and small group teaching
      between those interested in psychiatry and those not. Experience of 'enrichment
      activities' (psychiatry special study modules or components, psychiatric
      research, university psychiatry clubs, and psychiatry electives) were
      significantly more likely to take up psychiatry. Causality cannot, however, be
      determined in this study. The study identified several distinct groups of UK
      students: those deciding on psychiatry before medical school and maintaining that
      career choice, those deciding on psychiatry during medical school, and those
      interested in other fields. Addressing psychiatry teaching and exposure may
      improve recruitment into the speciality.

PMID- 24032500
TI  - Attracting young academics into the field of psychiatry and psychotherapy in
      Switzerland--the Zurich 'Study Focus on Psychiatry' and training concept for
      medical psychotherapy.
AB  - For several years the demand regarding psychiatrists in Switzerland can only be
      satisfied by recruiting colleagues from other countries. Given the global
      increase of mental disorders, initiatives encouraging young academics to choose
      psychiatry as their speciality, and enhancing the attractiveness of our field,
      are urgently needed. Two projects for the promotion of young academics are
      presented in this paper, one working with medical students, the other with
      residents in psychiatry. The Zurich 'Study Focus on Psychiatry' provides medical
      students with knowledge and key competencies in psychiatry at an early stage of
      their undergraduate training. This way, students are offered an opportunity to
      have a thorough look into psychiatry as a clinical specialism and as a science.
      The three-year psychotherapy training curriculum in medical psychotherapy
      provides residents in psychiatry and psychotherapy with specific training in
      either cognitive behavioural, or psychodynamic, or systemic psychotherapy.
      Additionally, and independent of the psychotherapeutic orientation they have
      chosen, all trainees attend joint sessions focusing on generic elements of
      psychotherapy and facilitating a hands-on transfer of psychotherapeutic
      principles into their clinical routine. These two projects aim at enhancing the
      attractiveness of psychiatry and psychotherapy as a speciality, and thus
      contributing to the promotion of young academics.

PMID- 24032501
TI  - International study of student career choice in psychiatry (ISoSCCiP): results
      from Modena, Italy.
AB  - Italy was one of the 16 countries to take part in the International Study of
      Student Career Choice in Psychiatry (ISoSCCiP). This paper reports and comments
      on the IsoSCCiP data on Italian medical students. Italian final year medical
      students from the University of Modena and Reggio Emilia were asked to fill in an
      on-line questionnaire during the first semester of two consecutive academic years
      (2009-2010, 2010-2011). Step-wise logistic regressions were performed. Of the 231
      students invited, 106 returned completed questionnaires (response rate = 46.7%).
      Women constituted 66%, and mean age was 25.14 (SD = 1.15). Psychiatry was the
      second most common choice of possible career by students (5.7%, n = 6). Choosing
      psychiatry was predicted by having volunteered for further clinical/research
      activities in psychiatry (p = 0.01), believing that 'the problems presented by
      psychiatric patients are often particularly interesting and challenging' (p <
      0.01), and by accounts of personal/family experience with physical illness (p <
      0.01). Both personal factors and factors related to training may be involved in
      the choice of psychiatry among Italian medical students. Cultural and
      organizational specificities of Italian mental healthcare may be involved,
      particularly the strong tradition of social psychiatry.

PMID- 24032502
TI  - Encouraging French medical students to choose a career in psychiatry: how and
      why?
AB  - There is an increasing demand for psychiatrists in France. This paper reviews the
      reasons for French medical students choosing psychiatry and the rationale and
      mechanisms for encouraging them towards this medical speciality. The main factors
      associated with choosing psychiatry as a career are the quantity and quality of
      undergraduate training and placements in psychiatry, better attitudes towards
      psychiatry and more emphasis on a positive life/work balance. The quality of
      postgraduate training can also influence students' decisions. Medical students
      should be encouraged to choose psychiatry first to counterbalance the existing
      stigma towards mental illness within the society, but also towards psychiatry
      within the medical profession, and second because of the current decline in
      French medical demography. Ways to improve recruitment are a selection process
      that favours a large number of psychiatric trainees, and an increase in the
      quality and quantity of training. Providing medical students with relevant
      information about training in psychiatry, notably through a national trainees'
      association, will not only improve the quality of care by increasing recruitment
      in psychiatry, but also ensure that all future doctors are familiar with and
      develop positive attitudes towards mental health issues.

PMID- 24032503
TI  - Recruitment to psychiatry in the Czech Republic: 'waiting for resuscitation'?
AB  - Recruitment to psychiatry is becoming a serious obstacle in providing first-class
      mental health treatment in many countries worldwide. We attempt to address this
      burning issue by examining medical student's attitudes towards psychiatry and
      factors influencing their career choice in the Czech Republic. In 2010, 71
      students in their last year of medical school at the First Faculty of Medicine,
      Charles University, Prague were recruited in this quantitative cross-sectional
      online study. From the sample, 16% (n = 11) of students were considering
      psychiatry as a career path. An important factor in choosing psychiatry as a
      career path was personal/family presence of mental illness. Longer experience
      with psychiatry placement also contributed to the choice of psychiatry, as well
      as participation in elective courses or psychiatric research projects. Students
      considering psychiatry were less systematic compared to the group not considering
      psychiatry. Low reported levels of recruitment to psychiatry present a
      problematic issue in the Czech Republic. To make psychiatry more appealing to
      medical students, proactive steps by the relevant stakeholders need to be
      implemented. These strategies should include steps such as allocating more time
      for psychiatry in the medical curriculum, better quality of lectures, and the
      inclusion of additional elective courses.

PMID- 24032504
TI  - Are there future psychiatrists among medical students in Croatia? The role of
      premedical and medical factors on career choice in psychiatry.
AB  - Despite the high prevalence of mental disorders, a worldwide shortage of
      psychiatrists exists. Moreover, the number of students interested in choosing
      psychiatry as their future profession is low and psychiatry is frequently
      regarded as one of the least wanted medical specializations. We report the
      findings of a cross-sectional quantitative survey of final year Croatian medical
      students as part of the International Survey of Student Career Choice in
      Psychiatry (ISoSCCiP). The questionnaire consisted of three sections: socio
      demographic factors, psychiatric education during medical school, and attitudes
      and personality characteristics. Out of 200 students, 122 completed the
      questionnaire (response rate 61%). The overall student evaluation of the
      compulsory psychiatry curriculum was 'average'. Significantly higher ratings were
      reported by students who attended special psychiatry teaching modules, or felt
      more involved in the teaching of the subject. Poor evaluation of medical school
      psychiatric education significantly increased the likelihood of not choosing
      psychiatry as a future career. The choice of psychiatry was also predicted by
      attitudes towards psychiatry and by personal characteristics. In conclusion,
      student ratings of medical school psychiatric education and involvement in
      teaching appear to influence choice towards psychiatry. Addressing these issues
      may increase the number of students motivated to pursue psychiatry as their
      future career choice.

PMID- 24032505
TI  - Recruitment and training of psychiatrists in Hong Kong: what puts medical
      students off psychiatry--an international experience.
AB  - The Hospital Authority employs over 60,000 staff and manages 41 public hospitals
      and institutions, 47 specialist outpatient clinics and 74 general outpatient
      clinics throughout Hong Kong. It received HK$41.14 billion (L 3.475 billion) of
      funding from the government in the year 2012 to 2013, which represented 92% of
      its funding income (Census & Statistics Department, 2013). This public healthcare
      system uses 3% of the Hong Kong gross domestic product (GDP) to provide 88% of
      inpatient services and 28% outpatient services locally, while the private sector
      provides only 12% of inpatient services and 72% of outpatient services with 2.3%
      of GDP. There is a heavy reliance on the public sector to provide healthcare to
      most of the patients requiring more intensive hospitalization. Hong Kong
      currently only has about 280 specialists in psychiatry serving a population of
      over 7 million people, of whom 90 work in the private sector. According to the
      World Health Organization (WHO) Mental Health Atlas 2011 country profiles (WHO,
      2011), the number of psychiatrists per 100,000 population is 4.39, compared to
      12.76 in Australia, 10.1 in Japan, 5.12 in Korea, and 2.81 in Singapore. There is
      a shortage of psychiatrists, especially in the public mental health sector, which
      urgently needs to be tackled. This article looks at the current trend in
      psychiatry teaching and recruitment from medical school and the training scheme
      provided by the Hong Kong College of Psychiatrists.

PMID- 24032506
TI  - Psychiatry career in Brazil: regional disparities, differences and similarities
      in an international context.
AB  - This review explores the literature related to career choice of psychiatry in
      Brazil through selection of scientific articles published in the period from 1999
      to 2013 in the MEDLINE and SciELO databases. There are currently 145 medical
      schools in Brazil, the highest concentration being in the more developed areas.
      In 2005, there were 6,003 psychiatrists working in Brazil, a rate of 3.3
      psychiatrists per 100,000 inhabitants, with unequal distribution across the
      geographical regions of the country: a rate of 4.5 psychiatrists/100,000
      inhabitants in the southern region, and less than one psychiatrist per 100,000
      inhabitants in the northern region. The south and south-east regions comprise 56%
      of the national population and 76% of the residency posts in psychiatry. In 2013,
      27% of the residency posts in psychiatry were not filled, particularly in the
      north and north-east areas, where the shortage of professionals is more
      pronounced. The number of specialized doctors is far below what is needed to
      cover the burden attributed to neuropsychiatric disorders in the country. The
      main hypotheses to explain this imbalance in Brazil are the relatively low
      exposure to the speciality during undergraduate course work, the stigma attached
      to mental disorders, and the poor organization of mental healthcare services.

PMID- 24032507
TI  - Seizure predisposition after perinatal hypoxia: effects of subsequent age and of
      an epilepsy predisposing gene mutation.
AB  - PURPOSE: There is a gap in our knowledge of the factors that modulate the
      predisposition to seizures following perinatal hypoxia. Herein, we investigate in
      a mouse model the effects of two distinct factors: developmental stage after the
      occurrence of the perinatal insult, and the presence of a seizure predisposing
      mutation. METHODS: Effects of age: P6 (postnatal day 6) mouse pups were subjected
      to acute hypoxia down to 4% O2 over the course of 45 min. Seizure
      susceptibilities to flurothyl-induced seizures (single exposures) and to
      flurothyl kindling were determined at specific subsequent ages. Effects of
      mutation: Heterozygote mice, with deletion of one copy of the Kcn1a gene,
      subjected to P6 hypoxia were compared as adults to wild-type mice with respect to
      susceptibility to a single exposure to flurothyl and to the occurrence of
      spontaneous seizures as detected by hippocampal electroencephalography (EEG) and
      video recordings. KEY FINDINGS: Effects of age: As compared to controls, wild
      type mice exposed to P6 hypoxia had a shortened seizure latency in response to a
      single flurothyl exposure at P50, but not at P7 or P28 (p < 0.04). In addition,
      perinatal hypoxia at P6 enhanced the rate of development of flurothyl kindling
      performed at P28-38 (p < 0.03), but not at P7-17. Effects of mutation: Kcn1a
      heterozygous mice subjected to P6 hypoxia exhibited increased susceptibility to
      flurothyl-induced seizures at P50 as compared to Normoxia heterozygote
      littermates, and to wild-type Hypoxia and Normoxia mice. In addition,
      heterozygotes exposed to P6 hypoxia were the only group in which spontaneous
      seizures were detected during the period of long-term monitoring (p < 0.027 in
      all comparisons). SIGNIFICANCE: Our data establish a mouse model of mild
      perinatal hypoxia in which we document the following: (1) the emergence, after a
      latent period, of increased susceptibility to flurothyl-induced seizures, and to
      flurothyl induced kindling; and (2) an additive effect of a gene mutation to the
      seizure predisposing consequences of perinatal hypoxia, thereby demonstrating
      that a modifier (or susceptibility) gene can exacerbate the long-term
      consequences of hypoxic injury.

PMID- 24032508
TI  - Imidazoles as promising scaffolds for antibacterial activity: a review.
AB  - In the last few decades, a lot of work has been done on heterocycles, especially
      the imidazole ring, to obtain a scaffold with potential pharmacological
      properties such as antibacterial, antifungal, anticancer, antiviral, antidiabetic
      and others, with lesser side effects. The search for new biologically active
      imidazoles continues to be an interesting area of investigation in medicinal
      chemistry. The present paper aims to bring together and discuss the wealth of
      information on antibacterial profile of imidazoles. So it can be employed for
      future development to obtain new potent drug molecules. 

PMID- 24032509
TI  - Antiviral medication in sexually transmitted diseases. Part I: HSV, HPV.
AB  - Sexually transmitted diseases (STD) are one of the most prevalent infectious
      diseases in the world and important cause of morbidity and mortality. Especially
      STDs of viral etiology are difficult to cure. In many cases the antiviral therapy
      can relieve the symptoms but not eliminate the virus. During the past decades,
      considerable progress has been made in the development of antiviral drugs. One of
      the oldest antiviral medications is acyclovir (ACV). It is approved to treat
      initial and recurrent genital herpes and as a suppressive therapy in severe
      recurrent genital infections as well. Drug resistance to ACV and related drugs is
      seen among immunocompromised hosts, including human immunodeficiency virus HIV
      infected patients. Resistant infections can be managed by second-line drugs -
      foscarnet or cidofovir- but they are more toxic than ACV. In case of HPV there is
      not known specific target for the medication and that is why the substances used
      in human papilloma virus HPV infection therapy are either antimitotics or
      immunomodulators. The Part I review focuses on mechanisms of actions and
      mechanisms of resistance to antiviral agents used in a treatment of the genital
      herpes and genital HPV infection. In Part II we will show the therapeutic options
      in other sexually transmitted infections: hepatitis B, C and HIV. 

PMID- 24032510
TI  - Development of ribonucleotide reductase inhibitors: a review on structure
      activity relationships.
AB  - Ribonucleotide reductase (RNR, E.C. 1.17.4.1), which is composed of two
      dissimilar proteins (subunits), often referred as R1 (containing polythiols) and
      R2 (containing non-heme iron and a free tyrosyl radical), which contribute to the
      role played by the enzyme. RNRs are one of the important targets in anticancer
      and antiviral drug development and many RNR inhibitors have been discovered at
      the end of the 20(th) century; many of them are already in clinical use. Triapine
      (3-AP) is one of the important RNR inhibitors belonging to the class of
      thiosemicarbazone derivatives, used in the treatment of various cancers. The
      structure activity relationship (SAR) studies on the investigated RNR inhibitors
      showed that the nitrogen atom in the pyridine (or other heterocycles) forms
      coordination complexes with the metal ions along with the imine, oxo and thio
      atoms of the thiosemicarbazone or semicarbazone pharmacophores. The computational
      analyses results in the adenine and purine derivatives suggest that the nitrogen
      atoms in the adenine rings make several hydrogen bonds with the water molecules
      present in the active site, as well as Gly249 and Glu288 residues. The OH group
      in third position of the sugar moiety interacts with the Ser217 (C=O) and the
      water molecules through hydrogen bonds. The aromatic rings in the molecules
      interact with the tyrosine residues. The thiosemicarbazone or semicarbazone
      derivatives explain that the flexibility and polar properties in the
      thiosemicarbazone or semicarbazone pharmacophoric regions allow the molecules to
      coordinate with the metal ion (especially iron) present in the RNR enzymes. This
      review concluded that RNR inhibitors composed of different fragments such as
      aryl, heteroaryl, sugar moiety, polar groups, flexible bonds, etc which are
      required for the binding of the molecules to the RNR enzymes. Further, the
      fragmental analysis of the RNR inhibitors on different toxicological and
      metabolic targets can provide significant novel molecules with acceptable
      pharmacokinetic properties. 

PMID- 24032511
TI  - The progress towards the development of DHQO derivatives and related analogues
      with inotropic effects.
AB  - During the course of the past two decades, our group has worked towards the
      development of increasingly potent inotropic agents by making structural
      modifications to compounds derived from 3,4-dihydro-2(1H)-quinolinone (DHQO) and
      related analogues. Herein, we describe the design and synthesis of a new series
      of DHQO derivatives and the subsequent evaluation of their positive inotropic
      activity towards left atrium stroke volume in isolated rabbit-heart preparations.
      Some of these derivatives presented favorable in vitro activities compared with
      the reference drug, milrinone, and compound 10a, in particular is currently being
      investigated as a preclinical drug candidate. This review also describes our
      progress towards the development of DHQO derivatives and related analogues with
      positive inotropic activities from 1999 to 2013. 

PMID- 24032512
TI  - Comprehensive Review on Natural beta-Carbolines as Anti-Malarial Agents.
AB  - Malaria is one of the major health problems in developing countries. It kills 1-2
      million people every year and also it affects financially status of many
      countries. Developed resistance to aminoquinoline(chloroquine), quinoline
      methanols (Quinine, Mefloquine) created troubles in malarial chemotherapy and
      signs of appearance of resistance to artemisinin based combination therapy (ACT)
      created emergency to develop novel antimalarial agents with high efficacy before
      spreading of resistance to ACT. From the ages natural products played important
      role in antimalarial therapy, identification of natural products, semisynthetic
      and synthetic analogs with potent antiplasmodium activity is one of the best
      method to develop novel antimalarial agents. In this review, we are presenting
      the antimalarial activity of natural beta-carboline alkaloids and special
      interest on manzamine alkaloids and their structure activity relationship.

PMID- 24032513
TI  - Triglyceride Metabolism and Hepatic Diseases.
AB  - Triglycerides participate in key metabolic functions such as energy storage,
      thermal insulation and as deposit for essential and non-essential fatty acids
      that can be used as precursors for the synthesis of structural and functional
      phospholipids. The liver is a central organ in the regulation of triglyceride
      metabolism, and it participates in triglyceride synthesis, export, uptake and
      oxidation. The metabolic syndrome and associated diseases are among the main
      concerns of public health worldwide. One of the metabolic syndrome components is
      impaired triglyceride metabolism. Diseases associated with the metabolic syndrome
      promote the appearance of hepatic alterations e.g., non-alcoholic steatosis,
      steatohepatitis, fibrosis, cirrhosis and cancer. In this article, we review the
      molecular actions involved in impaired triglyceride metabolism and its
      association with hepatic diseases. We discuss mechanisms that reconcile the
      chronic inflammation and insulin resistance, and new concepts on the role of
      intestinal micro-flora permeability and proliferation in fatty liver etiology. We
      also describe the participation of oxidative stress in the progression of events
      leading from steatosis to steatohepatitis and fibrosis. Finally, we provide
      information regarding the mechanisms that link fatty acid accumulation during
      steatosis with changes in growth factors and cytokines that lead to the
      development of neoplasticcells. One of the main medical concerns vis-a-vishepatic
      diseases is the lack of symptoms at the onset of the illness and, as result, its
      late diagnosis. The understandings of the molecular mechanisms that underlie
      hepatic diseases could help design strategies towards establishing markers for
      their accurate and timely diagnosis.

PMID- 24032514
TI  - Colonic drug delivery systems based on natural polysaccharides and their
      evaluation.
AB  - Natural polysaccharides are found in abundance, are inexpensive, safe and
      available in a variety of structures which can easily be modified chemically and
      biochemically. A number of natural gums and mucilages along with their chemically
      modified forms have been evaluated as controlled drug delivery devices. They are
      reported to be capable of providing the desired drug release profiles and in some
      cases, have shown comparable drug release properties with currently available
      sustained release products in the market. Colon specific drug delivery based on
      natural polysaccharides has highly been acclaimed in recent years. A colon
      specific drug delivery system should prevent drug release in the stomach as well
      as the small intestine. Several polysaccharides have been reported to be capable
      of preventing drug release in the upper GI tract while being susceptible to
      enzymatic degradation by colonic bacterial enzymes. A wide range of natural or
      modified polysaccharides has been investigated for peroral delivery of drugs to
      the colon. As the release of drug from these polysaccharides based systems is
      independent of pH and gastric emptying time these polysaccharides based systems
      are considered the most effective and preferable means for colonic drug delivery
      in terms of target specificity. 

PMID- 24032515
TI  - Benzopyran derivatives as cardio-selective ATP-sensitive potassium channel
      openers: a review.
AB  - Benzopyran derivatives are the potassium channel openers (KCOs) having
      antihypertensive, cardio-protective, myocardial protectors, powerful peripheral
      vasodilators and anti-ischemic activity. Their usage as anti-ischemic including
      angina, hypertension and diabetes is thought to be due to the stimulation of KATP
      channels which are contemplated to produce vasorelaxation and myocardial
      protection. It is observed that potassium channels are involved in mediating the
      cardio-protective effects of pre-conditioning in animal models and man. KCOs
      protect heart from an ischemic insult without contribution from vasodilatation.
      This review provides an overview of the characteristics of KCOs and their actions
      on subtypes used widely for the treatments of various diseases including
      hypertension, cardiac ischemia, arrhythmia, smooth muscle relaxation, diabetes,
      cardio-protective and anti-angiogenic activities. 

PMID- 24032516
TI  - Saponins: the potential chemotherapeutic agents in pursuing new anti-glioblastoma
      drugs.
AB  - Saponins are natural glycosides consisting of a triterpene or steroid aglycone
      with a range of pharmacological properties such as significant anti-tumor
      activity. In this article, we review our recent progress in the studies of the
      saponins possessing anticancer effects, especially anti-glioblastoma effects from
      twelve species of marine organisms and terrestrial plants. The anti-glioblastoma
      active saponins discovered by other researchers in recent decades are also
      reviewed and compared. Systematic extraction, isolation and structural
      elucidation on the saponin constituents from three species of starfishes, five
      species of sea cucumbers and four species of medicinal plants led to the
      identification of more than 129 saponins, among which 76 saponins are new
      compounds. Most of the new compounds were found to possess relatively rare
      structural features showing in vitro cytotoxicity against tumor cells, especially
      glioblastoma cells. Several saponins exhibited significant anti-glioblastoma
      effects in vivo by in situ administration (interstitial chemotherapy) and their
      haemolytic side effects were avoided in the tests. Multiple mechanisms of action,
      such as interfering with cell cycle progression, inducing apoptosis, promoting
      stabilization of microtubule, as well as several signal transduction pathways,
      were involved in their anticancer effects. The review provided valuable leads for
      pursuing new anti-glioblastoma drugs, and established a new viewpoint for further
      development of these marine and terrestrial organisms. The successful approach to
      administrate saponins in situ conquered the bottleneck in the development of
      saponins as new drugs- haemolytic effects. It means that saponins may be
      developed as potential chemotherapeutic agents in pursuing new antiglioblastoma
      drugs. 

PMID- 24032517
TI  - Molecular recognition in a diverse set of protein-ligand interactions studied
      with molecular dynamics simulations and end-point free energy calculations.
AB  - End-point free energy calculations using MM-GBSA and MM-PBSA provide a detailed
      understanding of molecular recognition in protein-ligand interactions. The
      binding free energy can be used to rank-order protein-ligand structures in
      virtual screening for compound or target identification. Here, we carry out free
      energy calculations for a diverse set of 11 proteins bound to 14 small molecules
      using extensive explicit-solvent MD simulations. The structure of these complexes
      was previously solved by crystallography and their binding studied with
      isothermal titration calorimetry (ITC) data enabling direct comparison to the MM
      GBSA and MM-PBSA calculations. Four MM-GBSA and three MM-PBSA calculations
      reproduced the ITC free energy within 1 kcal.mol(-1) highlighting the challenges
      in reproducing the absolute free energy from end-point free energy calculations.
      MM-GBSA exhibited better rank-ordering with a Spearman rho of 0.68 compared to
      0.40 for MM-PBSA with dielectric constant (epsilon = 1). An increase in epsilon
      resulted in significantly better rank-ordering for MM-PBSA (rho = 0.91 for
      epsilon = 10), but larger epsilon significantly reduced the contributions of
      electrostatics, suggesting that the improvement is due to the nonpolar and
      entropy components, rather than a better representation of the electrostatics.
      The SVRKB scoring function applied to MD snapshots resulted in excellent rank
      ordering (rho = 0.81). Calculations of the configurational entropy using normal
      mode analysis led to free energies that correlated significantly better to the
      ITC free energy than the MD-based quasi-harmonic approach, but the computed
      entropies showed no correlation with the ITC entropy. When the adaptation energy
      is taken into consideration by running separate simulations for complex, apo, and
      ligand (MM-PBSAADAPT), there is less agreement with the ITC data for the
      individual free energies, but remarkably good rank-ordering is observed (rho =
      0.89). Interestingly, filtering MD snapshots by prescoring protein-ligand
      complexes with a machine learning-based approach (SVMSP) resulted in a
      significant improvement in the MM-PBSA results (epsilon = 1) from rho = 0.40 to
      rho = 0.81. Finally, the nonpolar components of MM-GBSA and MM-PBSA, but not the
      electrostatic components, showed strong correlation to the ITC free energy; the
      computed entropies did not correlate with the ITC entropy. 

PMID- 24032520
TI  - The importance of clear language.

PMID- 24032518
TI  - Peptidylglycine alpha-amidating monooxygenase heterozygosity alters brain copper
      handling with region specificity.
AB  - Copper (Cu), an essential trace element present throughout the mammalian nervous
      system, is crucial for normal synaptic function. Neuronal handling of Cu is
      poorly understood. We studied the localization and expression of Atp7a, the major
      intracellular Cu transporter in the brain, and its relation to peptidylglycine
      alpha-amidating monooxygenase (PAM), an essential cuproenzyme and regulator of Cu
      homeostasis in neuroendocrine cells. Based on biochemical fractionation and
      immunostaining of dissociated neurons, Atp7a was enriched in post-synaptic
      vesicular fractions. Cu followed a similar pattern, with ~ 20% of total Cu in
      synaptosomes. A mouse model heterozygous for the Pam gene (PAM+/-) was
      selectively Cu deficient in the amygdala. As in cortex and hippocampus, Atp7a and
      PAM expression overlap in the amygdala, with highest expression in interneurons.
      Messenger RNA levels of Atox-1 and Atp7a, which deliver Cu to the secretory
      pathway, were reduced in the amygdala but not in the hippocampus in PAM+/- mice,
      GABAB receptor mRNA levels were similarly affected. Consistent with Cu
      deficiency, dopamine beta-monooxygenase function was impaired as evidenced by
      elevated dopamine metabolites in the amygdala, but not in the hippocampus, of
      PAM+/- mice. These alterations in Cu delivery to the secretory pathway in the
      PAM+/- amygdala may contribute to the physiological and behavioral deficits
      observed. Atp7a, a Cu-transporting P-type ATPase, is localized to the trans-Golgi
      network and to vesicles distributed throughout the dendritic arbor. Tissue
      specific alterations in Atp7a expression were found in mice heterozygous for
      peptidylglycine alpha-amidating monooxygenase (PAM), an essential neuropeptide
      synthesizing cuproenzyme. Atp7a and PAM are highly expressed in amygdalar
      interneurons. Reduced amygdalar expression of Atox-1 and Atp7a in PAM
      heterozygous mice may lead to reduced synaptic Cu levels, contributing to the
      behavioral and neurochemical alterations seen in these mice.

PMID- 24032519
TI  - Disrupted pulmonary artery cyclic guanosine monophosphate signaling in mice with
      hyperoxia-induced pulmonary hypertension.
AB  - Pulmonary hypertension (PH) occurs in 25 to 35% of premature infants with
      significant bronchopulmonary dysplasia (BPD). Neonatal mice exposed to 14 days of
      hyperoxia develop BPD-like lung injury and PH. To determinne the impact of
      hyperoxia on pulmonary artery (PA) cyclic guanosine monophosphate (cGMP)
      signaling in a murine model of lung injury and PH, neonatal C57BL/6 mice were
      placed in room air, 75% O2 for 14 days (chronic hyperoxia [CH]) or 75% O2 for 24
      hours, followed by 13 days of room air (acute hyperoxia with recovery [AHR]) with
      or without sildenafil. At 14 days, mean alveolar area, PA medial wall thickness
      (MWT), right ventricular hypertrophy (RVH), and vessel density were assessed. PA
      protein was analyzed for cGMP, soluble guanylate cyclase, and PDE5 activity. CH
      and AHR mice had RVH, but only CH mice had increased alveolar area and MWT and
      decreased vessel density. In CH and AHR PAs, soluble guanylate cyclase activity
      was decreased, and PDE5 activity was increased. In CH mice, sildenafil attenuated
      MWT and RVH but did not improve mean alveolar area or vessel density. In CH and
      AHR PAs, sildenafil decreased PDE5 activity and increased cGMP. Our results
      indicate that prolonged hyperoxia leads to lung injury, PH, RVH, and disrupted PA
      cGMP signaling. Furthermore, 24 hours of hyperoxia causes RVH and disrupted PA
      cGMP signaling that persists for 13 days. Sildenafil reduced RVH and restored
      vascular cGMP signaling but did not attenuate lung injury. Thus, hyperoxia can
      rapidly disrupt PA cGMP signaling in vivo with sustained effects, and concurrent
      sildenafil therapy can be protective. 

PMID- 24032521
TI  - Continuation of TNF blockade in patients with inflammatory rheumatic disease. An
      observational study on surgical site infections in 1,596 elective orthopedic and
      hand surgery procedures.
AB  - BACKGROUND: Increased infection risk in inflammatory rheumatic diseases may be
      due to inflammation or immunosuppressive treatment. The influence of tumor
      necrosis factor (TNF) inhibitors on the risk of developing surgical site
      infections (SSIs) is not fully known. We compared the incidence of SSI after
      elective orthopedic surgery or hand surgery in patients with a rheumatic disease
      when TNF inhibitors were continued or discontinued perioperatively. PATIENTS AND
      METHODS: We included 1,551 patients admitted for elective orthopedic surgery or
      hand surgery between January 1, 2003 and September 30, 2009. Patient demographic
      data, previous and current treatment, and factors related to disease severity
      were collected. Surgical procedures were grouped as hand surgery, foot surgery,
      implant-related surgery, and other surgery. Infections were recorded and defined
      according to the 1992 Centers for Disease Control definitions for SSI. In 2003
      2005, TNF inhibitors were discontinued perioperatively (group A) but not during
      2006-2009 (group B). RESULTS: In group A, there were 28 cases of infection in 870
      procedures (3.2%) and in group B, there were 35 infections in 681 procedures
      (5.1%) (p = < 0.05). Only foot surgery had significantly more SSIs in group B,
      with very low rates in group A. In multivariable analysis with groups A and B
      merged, only age was predictive of SSI in a statistically significant manner.
      INTERPRETATION: Overall, the SSI rates were higher after abolishing the
      discontinuation of anti-TNF perioperatively, possibly due to unusually low rates
      in the comparator group. None of the medical treatments analyzed, e.g.
      methotrexate or TNF inhibitors, were significant risk factors for SSI.
      Continuation of TNF blockade perioperatively remains a routine at our center.

PMID- 24032522
TI  - A micro-architectural evaluation of osteoporotic human femoral heads to guide
      implant placement in proximal femoral fractures.
AB  - BACKGROUND AND PURPOSE: The micro-architecture of bone has been increasingly
      recognized as an important determinant of bone strength. Successful operative
      stabilization of fractures depends on bone strength. We evaluated the osseous
      micro-architecture and strength of the osteoporotic human femoral head. MATERIAL
      AND METHODS: 6 femoral heads, obtained during arthroplasty surgery for femoral
      neck fracture, underwent micro-computed tomography (microCT) scanning at 30 MUm,
      and bone volume ratio (BV/TV), trabecular thickness, structural model index,
      connection density, and degree of anisotropy for volumes of interest throughout
      the head were derived. A further 15 femoral heads underwent mechanical testing of
      compressive failure stress of cubes of trabecular bone from different regions of
      the head. RESULTS: The greatest density and trabecular thickness was found in the
      central core that extended from the medial calcar to the physeal scar. This
      region also correlated with the greatest degree of anisotropy and proportion of
      plate-like trabeculae. In the epiphyseal region, the trabeculae were organized
      radially from the physeal scar. The weakest area was found at the apex and
      peripheral areas of the head. The strongest region was at the center of the head.
      INTERPRETATION: The center of the femoral head contained the strongest trabecular
      bone, with the thickest, most dense trabeculae. The apical region was weaker.
      From an anatomical and mechanical point of view, implants that achieve fixation
      in or below this central core may achieve the most stable fixation during
      fracture healing.

PMID- 24032523
TI  - Revision to reverse shoulder arthroplasty with retention of the humeral
      component.
AB  - BACKGROUND: Revision in failed shoulder arthroplasty often requires removal of
      the humeral component with a significant risk of fracture and bone loss. Newer
      modular systems allow conversion from anatomic to reverse shoulder arthroplasty
      with retention of a well-fixed humeral stem. We report on a prospectively
      evaluated series of conversions from hemiarthroplasty to reverse shoulder
      arthroplasty. METHODS: In 14 cases of failed hemiarthroplasty due to rotator cuff
      deficiency and painful pseudoparalysis (in 13 women), revision to reverse
      shoulder arthroplasty was performed between October 2006 and 2010, with retention
      of the humeral component using modular systems. Mean age at the time of operation
      was 70 (56-80) years. Pre- and postoperative evaluation followed a standardized
      protocol including Constant score, range of motion, and radiographic analysis.
      Mean follow-up time was 2.5 (2-5.5) years. RESULTS: Mean Constant score improved
      from 9 (2-16) to 41 (17-74) points. Mean lengthening of the arm was 2.6 (0.9-4.7)
      cm without any neurological complications. One patient required revision due to
      infection. INTERPRETATION: Modular systems allow retainment of a well-fixed
      humeral stem with good outcome. There is a risk of excessive humeral lengthening.

PMID- 24032524
TI  - Reduced length of hospital stay after the introduction of a rapid recovery
      protocol for primary THA procedures.
AB  - BACKGROUND AND PURPOSE: Rapid recovery protocols after total hip arthroplasty
      (THA) have been introduced worldwide in the last few years and they have reduced
      the length of hospital stay. We show the results of the introduction of a rapid
      recovery protocol for primary THA for unselected patients in our large teaching
      hospital. PATIENTS AND METHODS: In a retrospective cohort study, we included all
      1,180 patients who underwent a primary THA between July 1, 2008 and June 30,
      2012. These patients were divided into 3 groups: patients operated before,
      during, and after the introduction of the rapid recovery protocol. There were no
      exclusion criteria. All complications, re-admissions, and reoperations were
      registered and analyzed. RESULTS: The mean length of hospital stay decreased from
      4.6 to 2.9 nights after the introduction of the rapid recovery protocol. There
      were no statistically significant differences in the rate of complications, re
      admissions, or reoperations between the 3 groups. INTERPRETATION: In a large
      teaching hospital, the length of hospital stay decreased after introduction of
      our protocol for rapid recovery after THA in unselected patients, without any
      increase in complications, re-admissions, or reoperation rate.

PMID- 24032525
TI  - Humeral surface replacement for osteoarthritis.
AB  - BACKGROUND AND PURPOSE: Humeral resurfacing has shown promising results for
      osteoarthritis, but revisions for glenoid erosion have been reported frequently.
      We investigated the hypothesis that preoperative glenoid wear and postoperative
      progress of glenoid erosion would influence the clinical outcome. METHODS: We
      reviewed 61 resurfacing hemiarthroplasties (55 patients) for primary
      osteoarthritis. 6 patients were lost to follow-up and 5 had undergone revision
      arthroplasty. This left 50 shoulders in 44 patients (mean age 66 years) that were
      followed for mean 30 (12-44) months. Complications, revisions, and the age- and
      sex-related Constant score were assessed. Radiographs were evaluated for
      loosening and glenoid erosion according to Walch. RESULTS: Of the 50 shoulders
      that were functionally assessed, the average age- and sex-related Constant score
      was 73%. In patients with preoperative type-B2 glenoids, at 49% it was lower than
      in type-A1 glenoids (81%, p = 0.03) and in type-B1 glenoids (84%, p = 0.02). The
      average age- and sex-related Constant score for patients with type-A2 glenoids
      (60%) was lower than for type-A1 and -B1 glenoids and higher than for type-B2
      glenoids, but the differences were not statistically significant. In the total
      population of 61 shoulders, the radiographs showed postoperative glenoid erosion
      in 38 cases and no humeral prosthetic loosening. Revision arthroplasty was
      performed in 11 cases after 28 (7-69) months. The implant size had no
      statistically significant influence on the functional outcome. The size was
      considered to be adequate in 28 of the 50 functionally assessed shoulders. In 21
      cases, the implant size was too large and in 1 case it was too small.
      INTERPRETATION: We found frequent postoperative glenoid erosion and a high rate
      of revision arthroplasty after humeral resurfacing for primary osteoarthritis.
      Oversizing of the implants was common, but it had no statistically significant
      influence on the functional outcome. Inferior results were found in the presence
      of increased eccentric preoperative glenoid wear. Total shoulder arthroplasty
      should be considered in these patients.

PMID- 24032526
TI  - Duloxetine prophylaxis for episodic migraine in persons without depression: a
      prospective study.
AB  - OBJECTIVE: The objective of this pilot study is to evaluate the effects of daily
      duloxetine, 60-120 mg, on the frequency, duration, and severity of migraine
      attacks and the level of disability in episodic migraineurs. BACKGROUND: There is
      a need for more proven effective migraine preventive medications. Two
      antidepressants, both of which block serotonin and norepinephrine reuptake, have
      been shown to be effective in the preventive treatment of migraine. Neither has
      earned a level A recommendation in the 2012 guidelines of the American Academy of
      Neurology. Duloxetine also blocks serotonin and norepinephrine reuptake. METHODS:
      This was a prospective, 5-visit study on duloxetine treatment of episodic
      migraine headache with 4-10 migraine days, and less than 15 headache days per
      month. Patients were titrated to a goal dose of 120 mg. They were excluded if
      they had depression. RESULTS: There were 22 completers plus 5 subjects who took
      at least 1 dose of drug. The mean duloxetine dose was 110 mg. In a modified
      intent-to-treat analysis, subjects went from 9.2 +/- 2.7 headache days per month
      at baseline to 4.5 +/- 3.4 headache days per month (P < .001). There were no
      significant differences in the average headache duration, average headache
      severity, maximum headache attack severity, and level of functioning. Fifty-two
      percent of subjects had a 50% or greater improvement in headache days.
      CONCLUSIONS: Migraine prophylactic treatment with high-dose duloxetine may be
      effective in a nondepressed individual. The reported treatment response is in
      line with other commonly used migraine preventives.

PMID- 24032528
TI  - Evidence to challenge the universality of the Horiuti-Polanyi mechanism for
      hydrogenation in heterogeneous catalysis: origin and trend of the preference of a
      non-Horiuti-Polanyi mechanism.
AB  - The Horiuti-Polanyi mechanism has been considered to be universal for explaining
      the mechanisms of hydrogenation reactions in heterogeneous catalysis for several
      decades. In this work, we examine this mechanism for the hydrogenation of
      acrolein, the simplest alpha,beta-unsaturated aldehyde, in gold-based systems as
      well as some other metals using extensive first-principles calculations. It is
      found that a non-Horiuti-Polanyi mechanism is favored in some cases. Furthermore,
      the physical origin and trend of this mechanism are revealed and discussed
      regarding the geometrical and electronic effects, which will have a significant
      influence on current understandings on heterogeneous catalytic hydrogenation
      reactions and the future catalyst design for these reactions. 

PMID- 24032527
TI  - Natural killer T cell defects in multiple myeloma and the impact of lenalidomide
      therapy.
AB  - The causes of multiple myeloma (MM) remain obscure and there are few known risk
      factors; however, natural killer T (NKT) cell abnormalities have been reported in
      patients with MM, and therapeutic targeting of NKT cells is promoted as a
      potential treatment. We characterized NKT cell defects in treated and untreated
      patients with MM and determined the impact of lenalidomide therapy on the NKT
      cell pool. Lenalidomide is an immunomodulatory drug with co-stimulatory effects
      on NKT cells in vitro and is an approved treatment for MM, although its mode of
      action in that context is not well defined. We find that patients with
      relapsed/progressive MM had a marked deficiency in NKT cell numbers. In contrast,
      newly diagnosed patients had relatively normal NKT cell frequency and function
      prior to treatment, although a specific NKT cell deficiency emerged after high
      dose melphalan and autologous stem cell transplantation (ASCT) regimen. This also
      impacted NK cells and conventional T cells, but the recovery of NKT cells was
      considerably delayed, resulting in a prolonged, treatment-induced NKT cell
      deficit. Longitudinal analysis of individual patients revealed that lenalidomide
      therapy had no in-vivo impact on NKT cell numbers or cytokine production, either
      as induction therapy, or as maintenance therapy following ASCT, indicating that
      its clinical benefits in this setting are independent of NKT cell modulation.

PMID- 24032530
TI  - Improving the identification rate of endogenous peptides using electron transfer
      dissociation and collision-induced dissociation.
AB  - Tandem mass spectrometry (MS/MS) combined with bioinformatics tools have enabled
      fast and systematic protein identification based on peptide-to-spectrum matches.
      However, it remains challenging to obtain accurate identification of endogenous
      peptides, such as neuropeptides, peptide hormones, peptide pheromones, venom
      peptides, and antimicrobial peptides. Since these peptides are processed at sites
      that are difficult to predict reliably, the search of their MS/MS spectra in
      sequence databases needs to be done without any protease setting. In addition,
      many endogenous peptides carry various post-translational modifications, making
      it essential to take these into account in the database search. These
      characteristics of endogenous peptides result in a huge search space, frequently
      leading to poor confidence of the peptide characterizations in peptidomics
      studies. We have developed a new MS/MS spectrum search tool for highly accurate
      and confident identification of endogenous peptides by combining two different
      fragmentation methods. Our approach takes advantage of the combination of two
      independent fragmentation methods (collision-induced dissociation and electron
      transfer dissociation). Their peptide spectral matching is carried out separately
      in both methods, and the final score is built as a combination of the two
      separate scores. We demonstrate that this approach is very effective in
      discriminating correct peptide identifications from false hits. We applied this
      approach to a spectral data set of neuropeptides extracted from mouse pituitary
      tumor cells. Compared to conventional MS-based identification, i.e., using a
      single fragmentation method, our approach significantly increased the peptide
      identification rate. It proved also highly effective for scanning spectra against
      a very large search space, enabling more accurate genome-wide searches and
      searches including multiple potential post-translational modifications. 

PMID- 24032529
TI  - The role of dopamine D2, but not D3 or D4, receptor subtypes, in quinpirole
      induced inhibition of the cardioaccelerator sympathetic outflow in pithed rats.
AB  - BACKGROUND AND PURPOSE: Quinpirole (a dopamine D2-like receptor agonist) inhibits
      the cardioaccelerator sympathetic outflow in pithed rats by sympathoinhibitory D2
      like receptors. The present study was designed to identify pharmacologically the
      specific D2-like receptor subtypes (i.e. D2 , D3 and D4) involved in this
      sympathoinhibition by quinpirole. EXPERIMENTAL APPROACH: One hundred fourteen
      male Wistar rats were pithed, artificially ventilated with room air and prepared
      for either preganglionic spinal (C7-T1) stimulation of the cardioaccelerator
      sympathetic outflow (n = 102) or i.v. bolus injections of exogenous noradrenaline
      (n = 12). This approach resulted in frequency-dependent and dose-dependent
      tachycardic responses, respectively, as previously reported by our group. KEY
      RESULTS: I.v. continuous infusions of quinpirole (0.1-10 MUg kg(-1)  min(-1)),
      but not of saline (0.02 mL min(-1)), dose-dependently inhibited the
      sympathetically induced tachycardic responses. Moreover, the cardiac
      sympathoinhibition induced by 3 MUg kg(-1)  min(-1) quinpirole (which failed to
      affect the tachycardic responses to i.v. noradrenaline) was: (i) unchanged after
      i.v. injections of the antagonists SB-277011-A (D3 ; 100-300 MUg kg(-1)) or L
      745,870 (D4 ; 30-100 MUg kg(-1)); and (ii) markedly blocked and abolished by,
      respectively, 100 and 300 MUg kg(-1) of the D2 preferring receptor subtype
      antagonist L-741,626. These doses of antagonists, which did not affect per se the
      sympathetically induced tachycardic responses, were high enough to completely
      block their respective receptors. CONCLUSIONS AND IMPLICATIONS: The cardiac
      sympathoinhibition induced by 3 MUg kg(-1)  min(-1) quinpirole involves the
      dopamine D2 receptor subtype, with no evidence for the involvement of the D3 or
      D4 subtypes. This provides new evidence for understanding the modulation of the
      cardioaccelerator sympathetic outflow.

PMID- 24032531
TI  - Formulation of ciprofloxacin hydrochloride loaded biodegradable nanoparticles:
      optimization of technique and process variables.
AB  - Poly lactic-co-glycolic acid (PLGA 502 H) nanoparticles incorporating
      ciprofloxacin HCl (CP) were prepared by double emulsion solvent diffusion
      technique. METHODS: The influence of the application of probe sonication besides
      the high pressure homogenization in the preparation of the secondary emulsion and
      its application during the solidification step were studied. Their effect on the
      particle size, Zeta potential and the percent encapsulation efficiency of the
      drug (EE %) were investigated. The effect of the addition of polyvinyl alcohol
      (PVA) during the preparation of the primary emulsion was studied. Moreover, the
      effect of the addition of 0.1 M sodium chloride and/or adjusting the external and
      extracting phases to pH 7.4 were investigated. The selected formula was examined
      using IR, X-ray, DSC and SEM and in vitro drug release. RESULTS: These
      formulations showed an appropriate particle size ranges between 135.7-187.85 nm,
      a mean zeta potential ranging from -0.839 to -6.81 mV and a mean EE% which ranged
      from 35% to 69%. CONCLUSION: The presented data revealed the superiority of using
      probe sonication besides high pressure homogenization during the formation of
      secondary emulsion. Moreover, the results indicated that the tested factors had a
      pronounced significant effect on the EE%.

PMID- 24032532
TI  - Research progress on the mechanisms of combined bevacizumab and radiotherapy.
AB  - Bevacizumab, one of the best-known patents of VEGF inhibitor, has demonstrated
      significant radiosensitive effects on various preclinical tumor models and
      clinical trials recently. The radiosensitive effects of this novel patent have
      achieved satisfactory efficacy through the following mechanisms: normalization of
      the tumor vasculature, overcoming resistance to radiation, inhibition of
      repopulation after radiation, and blockade of radiation-induced increased VEGF
      expression. The combination of bevacizumab with radiotherapy in the treatment of
      malignant tumors was an inevitable path for the further clinical development of
      bevacizumab and a very good opportunity for improving the curative effect of
      radiotherapy. However, many questions such as those regarding the bevacizumab
      administration dosage and schedule, radio sensitivity efficacy evaluation and
      multi-target radiosensitive therapy need further research. The advent of
      bevacizumab combined with radiation has left physicians to encounter multiple
      challenges as well as opportunities for improving anti-cancer drug treatments. 

PMID- 24032533
TI  - T regulatory cells and related immunoregulatory factors in polymorphic light
      eruption following ultraviolet A1 challenge.
AB  - BACKGROUND: Polymorphic light eruption (PLE) is considered to be an autoimmune
      mediated skin condition in which the normal ultraviolet (UV)-induced local
      immunosuppression appears to be absent, leading to recognition of photoinduced
      autoantigens and subsequent inflammation. OBJECTIVES: To investigate T regulatory
      cells (Tregs) and related immunoregulatory factors in PLE lesions and controls.
      METHODS: Skin biopsies were performed in 13 patients with UVA1-challenged PLE, 12
      female patients with chronic discoid lupus erythematosus (CDLE) and 11 healthy
      controls who had exposure to UVA1. Immunohistochemistry and four-colour
      immunofluorescence studies were performed. RESULTS: Patients with CDLE and UVA1
      exposed controls showed significantly decreased epidermal immunoreactivity for
      CD1a compared with patients with PLE (P = 0.0001). Four-colour immunofluorescence
      revealed a median percentage of CD4+CD25+FOXP3+ Tregs of 7.6% (range 3.7-13.6%)
      in PLE, a median of 11.7% (range 9.5-13.9%) in CDLE and a median of 3.4% (range 0
      6.8%) in controls. Compared with UVA1-exposed controls, PLE and CDLE lesions
      showed significantly decreased transforming growth factor (TGF)-beta1
      immunoreactivity in the epidermis (P = 0.0003). In PLE lesions, we observed
      significantly decreased interleukin (IL)-10 expression compared with CDLE (P =
      0.022). In the dermis, receptor activator of nuclear factor-kappaB ligand (RANKL)
      expression was increased in UVA1-exposed controls compared with PLE and CDLE (P =
      0.018). CONCLUSIONS: Similar to CDLE lesions, UVA1-challenged PLE lesions display
      an altered immunoregulatory network, as indicated by decreased epidermal or
      dermal expression of TGF-beta1, IL-10 and RANKL, and a relatively low number of
      Tregs, particularly when compared with other inflammatory skin conditions
      reported in the literature.

PMID- 24032534
TI  - Crystalline phase modulates the potency of nanometric TiO2 to adhere to and
      perturb the stratum corneum of porcine skin under indoor light.
AB  - Nanometric TiO2 is largely employed in cosmetics, but in vitro toxic effects have
      been reported when nano-TiO2 is exposed to UV light. The photoreactivity of TiO2
      largely depends on its crystal phase, namely, anatase and rutile. Surface
      acidity, which is also dependent on crystal structure, may impart a positive or
      negative charge to the nanomaterial surface and ultimately modulate particle
      adhesion to tissues. Three nanometric TiO2 powders with a different crystal
      lattice and surface charge (anatase, rutile, and anatase/rutile) have been
      employed here to investigate their interaction with the skin and to examine the
      molecular mechanisms of the TiO2-induced oxidative damage. The strength of the
      interaction of nano-TiO2 with skin has been revealed by chemiometric mapping (MU
      XRF and SEM-EDS) after tissue washing. Positively charged anatase and
      anatase/rutile, but not negatively charged rutile, were strongly held on the skin
      surface and were able to promote a structural rearrangement of the lipid bilayer
      in the stratum corneum (DSC and Raman) under controlled indoor illumination (UVA
      < 1 mW/m2). Under the same conditions, cell-free reactivity tests (ROS-mediated
      free-radical release and lipoperoxidation) indicated that anatase and
      anatase/rutile are more reactive than rutile, suggesting a ROS-mediated oxidative
      mechanism that may alter the structure of the stratum corneum. Both the higher
      oxidative potential and the stronger adhesion to skin of anatase and
      anatase/rutile TiO2 may explain the stronger disorganization induced by these two
      samples and suggests the use of rutile to produce safer TiO2-based cosmetic and
      pharmaceutical products.

PMID- 24032535
TI  - Infrared spectra in the 3 MUm region of ethane and ethane clusters in helium
      droplets.
AB  - Ethane and ethane clusters (N ~ 10(2)-10(4)) were studied inside helium droplets
      with infrared laser spectroscopy. The spectra were measured in the 2880-3000 cm(
      1) range, which covers the nu5, nu(8+11), and nu7 vibrational bands of ethane.
      Partially resolved rotational fine structure in the spectrum of the monomer
      reveals solvent-induced band origin blue shifts that are each approximately 1 cm(
      1). The effective B(He) and A(He) rotational constants were found to be reduced
      by 52% and 16% in comparison to their gas phase values, respectively. Spectra of
      the clusters show the same three bands shifted toward low frequency by
      approximately 10 cm(-1) because of intermolecular interactions in the clusters.
      The spectra of the ethane clusters are dominated by the nu7 band, whereas the
      relative intensities of the nu5 and nu(8+11) bands are about a factor of 5 weaker
      than for single molecules or for solid ethane, the spectrum of which is also
      reported here.

PMID- 24032536
TI  - Natalizumab saturation: biomarker for individual treatment holiday after
      natalizumab withdrawal?
AB  - BACKGROUND: More and more patients with multiple sclerosis (MS) switch from
      natalizumab to fingolimod because of the risk of progressive multifocal
      leukoencephalopathy. The duration of the treatment holiday is still under debate
      referring to a possible recurrence of disease activity. AIM OF THE STUDY: The aim
      of this study was to evaluate the prognostic value of natalizumab saturation on T
      cells for the recurrence of clinical and radiological disease activity. METHODS:
      Cell surface-bound natalizumab saturation (in%) of CD8+ and CD4+ T cells from
      five patients with MS was determined before initiation of fingolimod by flow
      cytometry and related to clinical and MRI outcome during a 6-month follow-up.
      RESULTS: In two patients with either clinical or radiological disease activity,
      the natalizumab saturation on CD8+ and CD4+ T cells was <30%. In contrast, the
      remaining three patients with absence of disease activity had a median
      natalizumab saturation of 70% (range 59-79%) on CD4+ and 66% (range 52-68%) on
      CD8+ T cells. CONCLUSIONS: The data of this pilot study indicate that clinical
      and radiological disease activity is closely linked to natalizumab saturation at
      the time point of switch. The determination of natalizumab saturation may be an
      essential tool to monitor cessation of natalizumab treatment.

PMID- 24032537
TI  - Presentation and management of trapped neutrophil syndrome (TNS) in UK Border
      collies.
AB  - Three UK bred Border collie puppies were presented for investigation of pyrexia
      and severe lameness with associated joint swelling. Investigations revealed
      neutropenia, radiographic findings suggesting metaphyseal osteopathy, and
      polyarthritis and all dogs were subsequently confirmed with trapped neutrophil
      syndrome. Clinical improvement was seen after treatment with prednisolone and
      antibiotics and the dogs all survived to adulthood with a good short- to medium
      term outcome. Trapped neutrophil syndrome is an important differential diagnosis
      for young Border collie dogs in the UK presenting with pyrexia, neutropenia and
      musculoskeletal signs. 

PMID- 24032538
TI  - Clinical characteristics of pulsatile tinnitus caused by sigmoid sinus
      diverticulum and wall dehiscence: a study of 54 patients.
AB  - CONCLUSIONS: CT angiography (CTA) and digital subtraction angiography (DSA) are
      valuable tools in imaging work-ups for the diagnosis of sigmoid sinus
      diverticulum (SSD) and sigmoid sinus wall dehiscence (SSWD). The development of
      pulsatile tinnitus (PT) resulting from SSD and SSWD may be associated with the
      dominance of venous systems. OBJECTIVE: Our goal was to evaluate the clinical
      characteristics of PT caused by SSD and SSWD. METHODS: This was a retrospective
      chart review undertaken in a tertiary academic referral center. Fifty-four
      patients with PT due to SSD and SSWD were recruited. Hospital files of these
      patients were assessed. Data included medical history, physical examinations,
      auxiliary examinations, and radiographic findings of CTA and DSA. RESULTS: The
      study population comprised 51 females and 3 males. Most patients with PT caused
      by SSD and SSWD were middle-aged women. All had normal otoscopy results.
      Anomalies occurred in or adjacent to the region of the transverse-sigmoid sinus
      junction in 52 patients. Half of the patients (27/54) presented abnormal results
      of examination of blood lipids. There were 57.41% (31/54) cases with ipsilateral
      dominance of the venous system, 9.26% (5/54) cases with contralateral dominance,
      and 33.33% (18/54) cases with co-dominance of the venous system.

PMID- 24032539
TI  - Enhanced electrochemical performance of highly porous supercapacitor electrodes
      based on solution processed polyaniline thin films.
AB  - Enhancement to the electrochemical performance of supercapacitor electrodes were
      realized by incorporating highly porous conductive polymer films prepared with
      solution-processed polyaniline. The resultant nanostructures contained
      characteristic pores measuring 30-150 nm. Such electrodes generated from a
      solution of polyaniline-camphorsulfonic acid (PANI/CSA) exhibited higher porosity
      and electro-catalytic activity than those generated from conventional PANI
      nanomaterials. These improvements were attributed to faster ion diffusion at the
      PANI electrode/electrolyte interface. The highest specific capacitance observed
      for a supercapacitor fabricated with a porous PANI electrode obtained was 361 F
      g(-1) at 0.25 A g(-1), which is more than twice that of an equivalent electrode
      made with pristine PANI. Furthermore, supercapacitors made with highly porous
      PANI electrodes exhibited high electrochemical stability and rate performances. 

PMID- 24032540
TI  - Child cured of HIV: can this be repeated?
AB  - Eradication of HIV infection is the most challenging research area in the
      HIV/AIDS field. Treatment of HIV infection with antiretrovirals halts viral
      replication but fails to eradicate infection because it does not eliminate latent
      viruses. Eradication has only been achieved in one exceptional case after bone
      marrow transplantation. For this reason, researchers were surprised by a report
      describing the first cure of an HIV-infected individual using antiretrovirals. It
      was an in utero HIV-infected newborn treated immediately after birth with a
      potent antiretroviral combination. After treatment interruption, the child showed
      no evidence for active HIV infection; she was apparently cured. The case is
      particular and can be seen as an extreme case of postexposure prophylaxis.
      Moreover, due to strong immunological differences between newborns and adults,
      the case does not provide new hope for adult HIV-infected individuals, although
      it may open new treatment standards for functional cure of HIV-infected newborns.
      However, new studies to proof the benefit of immediate treatment of HIV-exposed
      newborns will require the definition of point of care diagnostic tools, drug
      regimens and the minimal time from birth to therapy introduction, and also
      importantly, when and under what settings should treatment be interrupted to test
      for functional cure. 

PMID- 24032541
TI  - A novel fluorescence imaging approach to monitor salt stress-induced modulation
      of ouabain-sensitive ATPase activity in sunflower seedling roots.
AB  - Seedlings exposed to salt stress are expected to show modulation of intracellular
      accumulation of sodium ions through a variety of mechanisms. Using a new
      methodology, this work demonstrates ouabain (OU)-sensitive ATPase activity in the
      roots of sunflower seedlings subjected to salt stress (120 mM NaCl). 9
      Anthroylouabain (a derivative of ouabain known to inhibit Na(+), K(+) -ATPase
      activity in animal systems, EC 3.6.3.9) has been used as a probe to analyze OU
      sensitive ATPase activity in sunflower (Helianthus annuus) seedling roots by
      spectrofluorometric estimation and localization of its spatial distribution using
      confocal laser scanning microscopy. Salt stress for 48 h leads to a significant
      induction of OU-sensitive ATPase activity in the meristematic region of the
      seedling roots. Calcium ions (10 mM) significantly inhibit enzyme activity and a
      parallel accumulation of sodium ions in the cytosol of the columella cells,
      epidermis and in the cells of the meristematic region of the roots is evident. As
      a rapid response to NaCl stress, the activity of OU-sensitive ATPase gets
      localized in the nuclear membrane of root protoplasts and it gets inhibited after
      treatment with calcium ions. Nuclear membrane localization of the OU-sensitive
      ATPase activity highlights a possible mechanism to efflux sodium ions from the
      nucleus. Thus, a correlation between OU-sensitive ATPase activity, its modulation
      by calcium ions and accumulation of sodium ions in various regions of the
      seedling roots, has been demonstrated using a novel approach in a plant system.

PMID- 24032542
TI  - Epilepsy in individuals with neurofibromatosis type 1.
AB  - PURPOSE: To describe the clinical characteristics and outcomes of individuals
      with neurofibromatosis type 1 (NF1) and seizures in the largest cohort reported
      to date. METHODS: A retrospective cross-sectional review of 536 individuals with
      NF1 was performed, and clinical data from 51 individuals with a history of at
      least one seizure were analyzed. KEY FINDINGS: In individuals with NF1, 9.5% had
      a history of at least one unprovoked seizure, and 6.5% had documented epilepsy.
      Individuals with seizures were more likely to have inherited NF1 from their
      mother (p = 0.001). Focal seizures were the most common type, occurring in 57% of
      individuals, although generalized seizures, specific electroclinical syndromes,
      and the presence of multiple seizure types were also noted. Moreover, in 21% of
      individuals with a previously unremarkable magnetic resonance imaging (MRI)
      study, neuroimaging at seizure onset revealed a new structural abnormality. In
      this population, 77% of individuals required multiple antiepileptic drugs (AEDs),
      and some required epilepsy surgery, with the best results following temporal lobe
      glioma resection. SIGNIFICANCE: Compared to the general population, seizures are
      more common in individuals with NF1, where they are often focal and related to an
      intracranial neoplasm. These observations suggest that all individuals with NF1
      and a new seizure should undergo MRI despite previous normal neuroimaging.
      Individuals with seizures and NF1 typically require more aggressive therapy than
      those without NF1 and should be considered for epilepsy surgery when appropriate.

PMID- 24032543
TI  - Peptide-catalyzed diastereo- and enantioselective cyclopropanation of aromatic
      alpha,beta-unsaturated aldehydes.
AB  - Highly diastereo- and enantioselective cyclopropanation of aromatic alpha,beta
      unsaturated aldehydes was achieved using a resin-supported peptide catalyst under
      aqueous conditions. In the peptide sequence, the residue possessing an oxygen
      atom with the appropriate length of the side chain was essential for attaining
      good diastereoselectivity. 

PMID- 24032544
TI  - The Notch signaling pathway: its role in focal CNS demyelination and
      apotransferrin-induced remyelination.
AB  - Oligodendroglial damage and demyelination are common pathological features
      characterizing white matter and neurodegenerative disorders. Identifying the
      signaling pathways involved in myelin repair through oligodendroglial progenitor
      maturation is essential for the development of new therapies. This article
      investigated the role of the Notch signaling pathway in CNS demyelination and
      apotransferrin-induced remyelination in a focal lysolecithin-induced
      demyelination model in rats. Notch was found activated in Nestin-expressing
      neural progenitor cells and in NG2-expressing oligodendroglial precursor cells in
      the subventricular zone and corpus callosum of lysolecithin-demyelinated rats.
      Notch activation seemed to be driven by Jagged1, which led to a high expression
      of downstream gene Hes5 in the subventricular zone of demyelinated rats.
      Apotransferrin injection induced remyelination, while the injection of the gamma
      secretase inhibitor reversed this effect. In addition, 24 h after apotransferrin
      injection, evidence showed Notch activation concomitantly with an increase in
      F3/contactin levels and the up-regulation of the myelin-associated glycoprotein
      gene in the subventricular zone and corpus callosum of demyelinated rats.
      Collected evidence supports the participation of both canonical and non-canonical
      Notch signaling pathways in demyelination/remyelination. Notch activation was
      found to trigger Hes5 expression as a consequence of focal demyelination, which
      might promote oligodendroglial precursor cell proliferation. During
      apotransferrin-induced remyelination, Notch activation seemed to be mediated by
      the expression of F3/contactin, which might induce apotransferrin-mediated
      oligodendroglial maturation. Evidence of the participation of Notch signaling in
      the demyelination/remyelination process will help further understand
      demyelinating disorders such as Multiple Sclerosis and the use of aTf should be
      taken into consideration as a possible therapeutic intervention.

PMID- 24032545
TI  - What about the neuroimaging findings in social anxiety disorder?
AB  - In the present article, structural, neurochemical and functional neuroimaging
      investigations performed on patients with social anxiety disorder were reviewed.
      A PubMed search was performed to identify all structural and functional
      neuroimaging studies published between 1980 and February 2013. The studies and
      case reports on neuroimaging in social anxiety disorder were grouped under the
      subheadings of structural, functional and magnetic resonance spectroscopic
      imaging. It seems that structural studies involve examination of abnormalities in
      the basal ganglia structures like caudate nucleus, thalamus, and putamen,
      hippocampus and amygdala abnormalities in summary. Neurochemical investigations
      reveal the deficiencies in the GABAergic system and over-activation in the
      glutamatergic system in social anxiety disorder. Functional neuroimaging
      investigations implicate the role of limbic-medial prefrontal circuit. 

PMID- 24032546
TI  - Somatic treatments excluding psychopharmacology in obsessive- compulsive
      disorder: a review.
AB  - Somatic treatments other than psychotropic drugs are increasingly used in the
      patients with obsessive compulsive disorder (OCD), however there has been little
      systematic review of them. Therefore, the present review deals with a variety of
      somatic treatment methods excluding psychotropic drugs. A literature search was
      performed on the PubMed database from the beginning of 1980, to September 2012,
      for published English, Turkish and French-language articles of somatic treatment
      approaches (excluding psychopharmacological agents) in the treatment of OCD. The
      search was carried out by using some terms in detail. Afterwards, the obtained
      investigations on electroconvusive therapy (ECT), deep brain stimulation (DBS),
      neurosurgical methods and transcranial magnetic stimulation (TMS) were presented.
      Although psychopharmacological treatment and psychotherapeutic approaches are
      primary treatment modalities in the management of OCD, other somatic treatment
      options seem to be used as alternatives, especially for patients with
      treatmentresistant OCD. 

PMID- 24032547
TI  - Stent-oriented versus patient-oriented outcome in patients undergoing early
      percutaneous coronary intervention for acute coronary syndrome: 2-year report
      from the BASE-ACS trial.
AB  - BACKGROUND: The BASE-ACS trial demonstrated an outcome of the titanium-nitride
      oxide-coated bioactive stents (BAS) statistically non-inferior to that of the
      everolimus-eluting stents (EES) at 12-month follow-up in patients presenting with
      acute coronary syndrome (ACS). We performed a post hoc analysis of the BASE-ACS
      trial with particular focus on stent-oriented versus patient-oriented outcome at
      24-month follow-up. METHODS: A total of 827 patients with ACS were randomly
      assigned to receive either BAS (417) or EES (410). Stent-oriented outcome was
      defined as a composite of cardiac death, target vessel-related non-fatal
      myocardial infarction, or ischemia-driven target lesion revascularization.
      Patient-oriented outcome was defined as a composite of all-cause death, any non
      fatal myocardial infarction, or any revascularization. RESULTS: Clinical follow
      up for 24 months was completed in 406 (97.4%) patients in the BAS group and in
      398 (97.1%) in the EES group. Stent-oriented outcome at 24-month follow-up
      occurred at similar frequencies in the two stent groups (10.1% for BAS versus
      11.2% for EES, P=0.53). Likewise, patient-oriented outcome at 24-month follow-up
      was similar in the two groups (16.3% versus 19.8%, respectively, P=0.2).
      CONCLUSIONS: In patients presenting with ACS, the rates of both stent-oriented
      and patient-oriented outcomes at 24-month follow-up in the BAS group were similar
      to those in the EES group.

PMID- 24032548
TI  - Molecular dynamics simulation and site-directed mutagenesis of alcohol
      acyltransferase: a proposed mechanism of catalysis.
AB  - Aroma in Vasconcellea pubescens fruit is determined by esters, which are the
      products of catalysis by alcohol acyltransferase (VpAAT1). VpAAT1 protein
      structure displayed the conserved HxxxD motif facing the solvent channel in the
      center of the structure. To gain insight into the role of these catalytic
      residues, kinetic and site-directed mutagenesis studies were carried out in
      VpAAT1 protein. Based on dead-end inhibition studies, the kinetic could be
      described in terms of a ternary complex mechanism with the H166 residue as the
      catalytic base. Kinetic results showed the lowest Km value for hexanoyl-CoA.
      Additionally, the most favorable predicted substrate orientation was observed for
      hexanoyl-CoA, showing a coincidence between kinetic studies and molecular docking
      analysis. Substitutions H166A, D170A, D170N, and D170E were evaluated in silico.
      The solvent channel in all mutant structures was lost, showing large differences
      with the native structure. Molecular docking and molecular dynamics simulations
      were able to describe unfavored energies for the interaction of the mutant
      proteins with different alcohols and acyl-CoAs. Additionally, in vitro site
      directed mutagenesis of H166 and D170 in VpAAT1 induced a loss of activity,
      confirming the functional role of both residues for the activity, H166 being
      directly involved in catalysis. 

PMID- 24032549
TI  - Control of PbSe nanorod aspect ratio by limiting phosphine hydrolysis.
AB  - The aspect ratio and yield of PbSe nanorods synthesized by the reaction of Pb
      oleate with tris(diethylamino)phosphine selenide are highly sensitive to the
      presence of water, making it critical to control the amount of water present in
      the reaction. By carefully drying the reaction precursors and then intentionally
      adding water back into the reaction, the nanorod aspect ratio can be controlled
      from 1.1 to 10 and the yield from 1 to 14% by varying the water concentration
      from 0 to 204 mM. (31)P{(1)H} and (1)H NMR show that water reacts with
      tris(diethylamino)phosphine to create bis(diethylamido)phosphorous acid. It was
      determined that bis(diethylamido)phosphorous acid is responsible for the observed
      aspect ratio and yield changes. Finally, it was found that excess oleic acid in
      the reaction can also react with tris(diethylamino)phosphine to create
      bis(diethylamido)phosphorous acid, and upon the removal of both excess oleic acid
      and water, highly uniform, nonbranching nanorods were formed. 

PMID- 24032550
TI  - Induction of estrogen-sensitive epithelial cells derived from human-induced
      pluripotent stem cells to repair ovarian function in a chemotherapy-induced mouse
      model of premature ovarian failure.
AB  - The incidence of premature ovarian failure (POF), a condition causing amenorrhea
      and hypergonadotropic hypoestrogenism in women before the age of 40, has been
      increasing in recent years. As an irreversible pathological change, improved
      treatment strategies for this disease are urgently needed. In this study, a type
      of microRNA (miR-17-3p) was used to guide the differentiation of human-induced
      pluripotent stem (iPS) cells into hormone-sensitive ovarian epithelial (OSE)-like
      cells in vitro. To prevent their morphological transformation into fibroblast
      like cells, MiR-17-3p, a microRNA that suppresses vimentin expression, was
      transfected into human iPS cells. Subsequently, these cells were successfully
      induced into OSE-like cells in vitro after treatment with estrogen and cell
      growth factors. Compared with controls, iPS cells transfected with miR-17-3p
      expressed higher levels of epithelial markers (cytokeratin 7, AE1, AE3, and E
      cadherin) and estrogen receptors (ERalpha and ERbeta) while levels of mesenchymal
      markers (fibronectin, vimentin, and N-cadherin) lowered after the induction. The
      human iPS cell-derived OSE-like cells were then injected into cyclophosphamide
      induced POF model mice to determine their potential benefit as grafts to repair
      ovarian tissues. The OSE-like cells survived within POF mouse ovaries for at
      least 14 days in vivo. Compared with the negative controls, expressions of
      cytokeratin 7 and ERbeta proteins were elevated while fibronectin and vimentin
      levels in ovarian tissues were downregulated in the OSE-like cell transplantation
      group. Moreover, the ovarian weight and plasma E2 level increased over time in
      the transplantation with OSE-like cells, compared with control groups. Hence, we
      can draw the conclusion that iPS cells can be induced to differentiate into OSE
      like cells in vitro. 

PMID- 24032552
TI  - Raman spectroscopy: new perspectives for its clinical application in diagnosis.

PMID- 24032551
TI  - Does the racial/ethnic composition of Medicare Advantage plans reflect their
      areas of operation?
AB  - OBJECTIVE: To assess the extent to which the racial/ethnic composition of
      Medicare Advantage (MA) plans reflects the composition of their areas of
      operation, given the potential incentives created by the Centers for Medicare &
      Medicaid Services' Quality Bonus Payments for such plans to avoid enrolling
      racial/ethnic minority beneficiaries. DATA SOURCES/STUDY SETTING: 2009 Medicare
      Consumer Assessment of Healthcare Providers and Systems (MCAHPS) survey and
      administrative data from the Medicare Enrollment Database. DATA
      COLLECTION/EXTRACTION METHODS: We defined each plan's area of operation as all
      counties in which it had MA enrollees, and we created a matrix of race/ethnicity
      by plan by county of residence to assess the racial/ethnic distribution of each
      plan's enrollees in comparison with the racial/ethnic composition of MA
      beneficiaries in its operational area. PRINCIPAL FINDINGS: There is little
      evidence that health plans are selectively underenrolling blacks, Latinos, or
      Asians to a substantial degree. A small but potentially important subset of plans
      disproportionately serves minority beneficiaries. CONCLUSIONS: These findings
      provide a baseline profile that will enable crucial ongoing monitoring to assess
      how the implementation of Quality Bonus Payments may affect MA plan coverage of
      minority populations.

PMID- 24032553
TI  - Long-term anti-FVIII antibody response in Bethesda-negative haemophilia A
      patients receiving continuous replacement therapy.
AB  - It has previously been shown that patients with haemophilia A may develop non
      neutralizing anti-factor VIII (FVIII) antibodies (NNA) that escape detection by
      the Bethesda assay, but are detected using immune-based assays. We and others
      found NNAs to be directed not only towards non-functional parts of the protein,
      but towards all regions of the FVIII protein. We also showed a heterogeneous
      antibody response towards different FVIII products. However, the clinical
      relevance and the natural history of NNA remain unclear. Therefore, we followed a
      cohort of unrelated subjects with haemophilia A for 4 years with the goal of
      exploring the long-term development of NNA using an enzyme-linked immunosorbent
      assay (ELISA). Ten of 78 subjects (12.8%) exhibited an immune response that was
      transient and heterogeneous, and none of the subjects developed an FVIII
      inhibitor. The result of the ELISA was examined in relation to clinical variables
      and no significant associations between a positive ELISA and age, F8 mutation,
      port-a-cath implantation and HCV infection were shown. Interestingly, patients
      with NNA had significantly fewer bleeding episodes (P = 0.048) compared with NNA
      negative subjects. The results indicate that the immune response to FVIII
      products within an individual may vary over time. However, the clinical impact of
      NNA remains unclear. 

PMID- 24032554
TI  - Early clinical response as a predictor of subsequent response to ixekizumab
      treatment: results from a phase II study of patients with moderate-to-severe
      plaque psoriasis.
AB  - BACKGROUND: Early identification of responsiveness to biologic treatments in
      psoriasis has significant clinical and economic implications. OBJECTIVES: To
      evaluate whether early clinical improvements in Psoriasis Area and Severity Index
      (PASI) scores could predict subsequent clinical responses in patients treated
      with ixekizumab, an anti-interleukin-17 monoclonal antibody. METHODS: This post
      hoc analysis was derived from a phase II study in patients with moderate-to
      severe plaque psoriasis (n = 114) who received multiple doses of ixekizumab 10,
      25, 75 or 150 mg subcutaneously over 20 weeks. PASI score improvements from
      baseline to weeks 2, 4 and 6 were evaluated to determine the optimal threshold
      for predicting subsequent PASI responses at week 12. RESULTS: Early clinical
      improvement in disease symptoms at weeks 4 and 6 was predictive of >= 75%
      improvement in PASI score (PASI 75) at week 12 with >= 90% predictability. A 40
      50% improvement in PASI (PASI 40 to PASI 50) from baseline to weeks 4 and 6 was
      the optimum range for predicting PASI 75 response at week 12. For all doses
      combined, achieving PASI 40 at week 4 or week 6 was associated with high negative
      predictive values (NPVs) (80% and 95%, respectively) and positive predictive
      values (PPVs) (89% and 84%, respectively). For all doses combined, achieving PASI
      50 at week 4 or week 6 was associated with NPVs of 71% and 89% and PPVs of 94%
      and 89%, respectively. Sensitivity analysis with the high-dose group (75 and 150
      mg) results confirmed these findings. CONCLUSIONS: Early clinical responses (and
      nonresponse) may help predict later clinical responses in patients treated with
      ixekizumab.

PMID- 24032555
TI  - Possible pathogenic role of T helper type 9 cells and interleukin (IL)-9 in
      atopic dermatitis.
AB  - T helper type 9 (Th9) cells are a novel identified subset of CD4(+) T helper
      cells, which could partly contribute to allergic inflammation, while the precise
      contribution of Th9 cells in atopic dermatitis (AD) remains unknown. We aimed to
      explore the possible role of Th9 cells in AD pathogenesis. The Th9 cell
      percentage, transcription factor PU.1 and cytokine interleukin (IL)-9 mRNA
      levels, as well as IL-9 serum concentration in peripheral circulation, were
      measured in AD patients, psoriasis patients and healthy controls. The Th9 cell
      percentage, PU.1 and IL-9 expression levels of AD patients were all increased
      significantly compared with the other two control groups (P < 0.01), and
      correlated positively with SCORing Atopic Dermatitis index, serum immunoglobulin
      (Ig)E and thymus- and activation-regulated chemokine (TARC) levels (P < 0.05). In
      simple AD patients and AD patients complicated by allergic rhinitis or asthma,
      there were no significant differences in the Th9 cell percentage, PU.1 and IL-9
      expression levels between them. At the same time, IL-9 and vascular endothelial
      growth factor (VEGF) mRNA levels were detected in AD lesions and normal skin
      samples, which were both distinctly elevated in AD lesions, and there was a
      positive association between them (P < 0.01). Keratinocytes were cultured with IL
      9 stimulation and the secretion of VEGF was detected. IL-9 can promote the
      secretion of VEGF by keratinocytes in a time- and dose-dependent manner. In
      conclusion, the expansion of the Th9 cell subset, up-regulation of the PU.1
      transcription factor and increased secretion of the IL-9 cytokine may contribute
      to the pathogenesis of AD, which may be supported by the increased release of
      VEGF by keratinocyes after IL-9 stimulation.

PMID- 24032556
TI  - Thiaplakortones A-D: antimalarial thiazine alkaloids from the Australian marine
      sponge Plakortis lita.
AB  - A high-throughput screening campaign using a prefractionated natural product
      library and an in vitro antimalarial assay identified active fractions derived
      from the Australian marine sponge Plakortis lita . Bioassay-guided fractionation
      of the CH2Cl2/CH3OH extract from P. lita resulted in the purification of four
      novel thiazine-derived alkaloids, thiaplakortones A-D (1-4). The chemical
      structures of 1-4 were determined following analysis of 1D/2D NMR and MS data.
      Comparison of the chiro-optical data for 3 and 4 with literature values of
      related N-methyltryptophan natural products was used to determine the absolute
      configuration for both thiaplakortones C and D as 11S. Compounds 1-4 displayed
      significant growth inhibition against chloroquine-sensitive (3D7) and chloroquine
      resistant (Dd2) Plasmodium falciparum (IC50 values <651 nM) and only moderate
      cytotoxicity against HEK293 cells (IC50 values >3.9 MUM). Thiaplakortone A (1)
      was the most active natural product, with IC50 values of 51 and 6.6 nM against
      3D7 and Dd2 lines, respectively. 

PMID- 24032558
TI  - Identification of octenal-related dA and dC adducts formed by reactions with a
      hemin-omega-6-fat peroxidation model system.
AB  - Deoxynucleosides were reacted in a lipid peroxidation model system, emulsified
      hemin-ethyl linoleate, and the adducts thus produced were analyzed by HPLC.
      Substantial amounts of stable adducts were detected in the dA- and dC-reaction
      mixtures. The structures of the major dA and dC adducts, other than the known 4
      oxo-2-nonenal adducts, were determined to be etheno-type adducts, with a C6 side
      chain bearing an alpha-hydroxyl-group. These results suggested that the substance
      involved in adduct formation is 2,3-epoxyoctanal. This compound showed
      mutagenicity in Salmonella strains TA 100 and TA 104 without the S-9 mix. In
      addition, based on the structure of a minor dC adduct, another possibly involved
      mutagen, 4-oxo-2-octenal, was proposed. These mutagens may be formed during
      storage and cooking of food, or during digestion, and may be involved in human
      cancers.

PMID- 24032561
TI  - Carbon nanotubes for the label-free detection of biomarkers.
AB  - Carbon nanotubes (CNTs) have been of high interest because of their potential to
      complement or to replace current biomedical sensor and assay techniques. By
      taking advantage of their unique electrical and optical properties, CNTs can be
      integrated into highly sensitive sensors and probes. We highlight recent advances
      toward applying CNTs to the biomedical field, focusing on a report by Reuel et
      al. in this issue of ACS Nano, wherein the inherent near-infrared (NIR)
      fluorescence of functionalized arrays of single-walled carbon nanotubes (SWNTs)
      is utilized for detection of several important biological markers. 

PMID- 24032559
TI  - The effect of lung deflation on the position of the pleura during subclavian vein
      cannulation in infants receiving mechanical ventilation: an ultrasound study.
AB  - We evaluated the effect of lung deflation on the relative position of the pleura
      compared with a reference line during supra- and infraclavicular approaches to
      the right subclavian vein. The reference line was drawn relative to the predicted
      pathway of the needle. The distances between the pleura and the reference line
      for supra- and infraclavicular approaches were measured during inspiration and
      expiration in 41 infants. Measurements were repeated with the application of 5
      cmH2O positive end-expiratory pressure (PEEP) and in the Trendelenburg position.
      Lung deflation during the supraclavicular approach significantly decreased the
      volume of lung crossing the reference line by a median (IQR [range]) of 1.0 (0.6
      to 1.3 [0.0 to 4.8]) mm, p < 0.001, irrespective of the application of PEEP or
      patient position. However, during the infraclavicular approach, lung deflation
      showed no change in the distance of the pleura from the reference line regardless
      of PEEP or patient position. We conclude that lung deflation moves the lung apex
      caudally and can reduce the potential risk of pneumothorax during a
      supraclavicular approach to the right subclavian vein in infants.

PMID- 24032557
TI  - Functionally biased signalling properties of 7TM receptors - opportunities for
      drug development for the ghrelin receptor.
AB  - The ghrelin receptor is a 7 transmembrane (7TM) receptor involved in a variety of
      physiological functions including growth hormone secretion, increased food intake
      and fat accumulation as well as modulation of reward and cognitive functions.
      Because of its important role in metabolism and energy expenditure, the ghrelin
      receptor has become an important therapeutic target for drug design and the
      development of anti-obesity compounds. However, none of the compounds developed
      so far have been approved for commercial use. Interestingly, the ghrelin receptor
      is able to signal through several different signalling pathways including Galphaq
      , Galphai/o , Galpha12/13 and arrestin recruitment. These multiple signalling
      pathways allow for functionally biased signalling, where one signalling pathway
      may be favoured over another either by selective ligands or through mutations in
      the receptor. In the present review, we have described how ligands and mutations
      in the 7TM receptor may bias the receptors to favour either one G-protein over
      another or to promote G-protein independent signalling pathways rather than G
      protein-dependent pathways. For the ghrelin receptor, both agonist and inverse
      agonists have been demonstrated to signal more strongly through the Galphaq 
      coupled pathway than the Galpha12/13 -coupled pathway. Similarly a ligand that
      promotes Galphaq coupling over Galphai coupling has been described and it has
      been suggested that several different active conformations of the receptor may
      exist dependent on the properties of the agonist. Importantly, ligands with such
      biased signalling properties may allow the development of drugs that selectively
      modulate only the therapeutically relevant physiological functions, thereby
      decreasing the risk of side effects. LINKED ARTICLES: This article is part of a
      themed section on Neuropeptides. To view the other articles in this section visit
      http://dx.doi.org/10.1111/bph.2013.170.issue-7.

PMID- 24032562
TI  - Electronic structure and optical properties of the thiolate-protected Au28(SMe)20
      cluster.
AB  - The recently reported crystal structure of the Au28(TBBT)20 cluster (TBBT: p-tert
      butylbenzenethiolate) is analyzed with (time-dependent) density functional theory
      (TD-DFT). Bader charge analysis reveals a novel trimeric Au3(SR)4 binding motif.
      The cluster can be formulated as Au14(Au2(SR)3)4(Au3(SR)4)2. The electronic
      structure of the Au14(6+) core and the ligand-protected cluster were analyzed,
      and their stability can be explained by formation of distorted eight-electron
      superatoms. Optical absorption and circular dichroism (CD) spectra were
      calculated and compared to the experiment. Assignment of handedness of the
      intrinsically chiral cluster is possible. 

PMID- 24032563
TI  - Introduction to a Virtual Special Issue to mark the publication of the 200(th)
      volume of New Phytologist.

PMID- 24032564
TI  - Cyanobacterial nitrogen fixation in association with feather mosses: moss as
      boss?

PMID- 24032565
TI  - Modulating effects of ontogeny on the outcome of plant-plant interactions along
      stress gradients.

PMID- 24032566
TI  - When paleontology and molecular genetics meet: a genetic context for the
      evolution of conifer ovuliferous scales.

PMID- 24032567
TI  - Therapeutic effect of adeno-associated virus (AAV)-mediated ADNF-9 expression on
      cochlea of kanamycin-deafened guinea pigs.
AB  - CONCLUSION: rAAV-NT4-ADNF-9 could ameliorate the damage to auditory function and
      repair previous impairment of cochlear hair cell loss induced by kanamycin.
      OBJECTIVE: To investigate the therapeutic effect of ADNF-9 on cochlear hair cells
      using the recombinant adeno-associated virus (AAV) carrying fusion gene NT4-ADNF
      9 and the kanamycin-deafened guinea pig model. METHODS: Forty white guinea pigs
      with normal auricle reflex and normal auditory brainstem responses (ABRs) were
      randomly divided into four groups. Kanamycin was administered to the animals in
      groups A, B, and C to establish the deafened guinea pig model. rAAV-NT4-ADNF-9,
      vector only, and artificial perilymph were then delivered to the cochlear tissue
      of animals in groups A, B, and C, respectively, through the round window
      membrane. Animals in group D did not receive any treatment and acted as normal
      controls. The hearing thresholds on the surgery side were recorded before and
      after the transfection treatment. Fourteen days after treatment, cochleae were
      removed for paraffin slide preparation and cochlear surface preparation. A phase
      contrast microscope was used to observe the protective effect of ADNF-9 on hair
      cells. RESULTS: Significant reduction of the ABR threshold was observed after
      rAAV-NT4-ADNF-9 treatment (p < 0.05). After 14 days of treatment, the ABR
      threshold was also significantly different between the rAAV-NT4-ADNF-9-infected
      group and the non-infected group. Moreover, phase contrast microscopy showed
      significantly less hair cell damage or hair cell loss in the group treated with
      rAAV-NT4-ADNF-9 than in the groups treated with vector only or artificial
      perilymph (p < 0.05).

PMID- 24032568
TI  - Relationship between tympanic membrane retraction and habitual sniffing in
      patients with cholesteatoma.
AB  - CONCLUSION: Habitual sniffing affects the pathogenicity and recurrence of
      cholesteatoma. Postoperative instructions requesting patients to cease sniffing
      may reduce the retraction and recurrence of cholesteatoma. OBJECTIVE: To examine
      the relationship between tympanic membrane retraction and habitual sniffing in
      patients with cholesteatoma. METHODS: We recruited 98 patients (102 ears) who
      were surgically treated for cholesteatoma by canal wall-down tympanoplasty (22
      ears) or canal wall-down tympanoplasty with reconstruction methods (80 ears). We
      classified these patients into two groups on the basis of their preoperative
      habitual sniffing: habitual and non-habitual sniffers. The findings of the
      contralateral tympanic membrane were examined in each group and were classified
      according to the Tos classifications. Next, we evaluated the incidence of 1-year
      postoperative tympanic membrane retraction treated by the canal-down
      tympanoplasty with reconstruction method in the following three groups: non
      habitual sniffing group, sniffing cessation group, and continual sniffing group.
      RESULTS: In habitual sniffers, the Tos classifications of contralateral tympanic
      membrane were normal in 7% (3/41). In contrast, for non-habitual sniffers, the
      findings were normal in 39% (21/54). These results indicate that sniffing causes
      tympanic membrane retraction. The tympanic membranes of patients in the sniffing
      cessation group were largely normal after surgery. However, more than 50% of the
      patients who continued to sniff after surgery showed retraction or recurrent
      cholesteatoma.

PMID- 24032569
TI  - Secondary endolymphatic hydrops after sudden deafness.
AB  - CONCLUSION: Patients with sudden deafness who had abnormal ocular vestibular
      evoked myogenic potential (oVEMP)/cervical VEMP (cVEMP) responses but retained
      caloric function may subsequently develop secondary hydrops with a mean interval
      of 8 years. OBJECTIVE: This study applied the inner ear test battery in patients
      who had sudden deafness previously to elucidate how secondary endolymphatic
      hydrops occurs years after sudden deafness. METHODS: Twenty patients who had
      experienced recent vertiginous attacks several years after sudden deafness (group
      A) and 20 patients without rotational vertiginous episode for at least 5 years
      following sudden deafness (group B) were enrolled. All patients underwent an
      inner ear test battery comprising audiometry, caloric test, and oVEMP and cVEMP
      tests. RESULTS: The mean interval from initial sudden deafness to vertiginous
      attack in group A was 8 years, with a mean hearing level of 66 +/- 20 dB, which
      did not significantly differ from 61 +/- 20 dB in group B. For the vestibular
      test results, the percentages of abnormal cVEMP, oVEMP, and caloric tests in
      group A were 65%, 70%, and 25%, respectively. Compared to the respective 70%,
      60%, and 75% abnormalities in group B, only the caloric test differed
      significantly.

PMID- 24032570
TI  - Multiplex analyses of cytokine and chemokine release from the cultured fibroblast
      of nasal polyps: the effect of IL-17A.
AB  - CONCLUSION: Our results demonstrate for the first time a potentially enhanced
      basal secretion of monocyte chemoattractant protein-1 (MCP-1) and interleukin
      (IL)-17A-stimulated secretion of IL-6 from nasal polyp fibroblasts, enhanced
      basal secretion of IL-6 from eosinophilic nasal polyp fibroblasts, and a
      remarkable up-regulation of IL-9 and granulocyte colony-stimulating factor (G
      CSF) from nasal fibroblasts by IL-17A stimulation. OBJECTIVES: The fibroblast,
      one of the main cell types making up nasal polyps, is thought to be a target cell
      of various cytokines. METHODS: Subcultured fibroblasts were established from
      human polyp biopsy tissues. Simultaneous quantification of 27 kinds of cytokines
      and chemokines in culture supernatants in unstimulated and IL-17A-stimulated
      conditions was performed with a human multiplex cytokine assay system. RESULTS:
      The IL-17A receptor was expressed at similar levels in all three groups. In the
      eosinophilic group, basal secretion levels of IL-6 were significantly higher than
      those in the control and non-eosinophilic groups. Basal secretion of MCP-1 in
      both the non-eosinophilic and eosinophilic groups was also higher than that of
      the control group. Both IL-9 and G-CSF secretion were remarkably enhanced by IL
      17A stimulation in all three groups. The receptor-mediated response by IL-17A
      significantly up-regulated IL-6 release alone in the non-eosinophilic and
      eosinophilic groups as compared with the control group.

PMID- 24032571
TI  - Relationship between extracapsular spread and FDG PET/CT in oropharyngeal
      squamous cell carcinoma.
AB  - CONCLUSION: Median maximum standardized uptake (SUVmax) cut-off values of FDG
      PET/CT higher than 3.85 were found to be associated with a greater risk cervical
      lymph node metastasis with extracapsular spread (ECS) in patients with
      oropharyngeal squamous cell carcinoma (OPSCC). OBJECTIVES: The purpose of this
      study was to evaluate the use of FDG PET/CT for the identification of ECS and to
      establish its histologic correlates in OPSCC. METHODS: The medical records of 78
      patients who underwent FDG PET/CT for OPSCC before surgery were reviewed.
      RESULTS: ECS was present in 42% (42/69) of dissected necks and in 51% (54/106) of
      dissected cervical levels. The SUVmax values of cervical lymph nodes with and
      without ECS were found to be significantly different (6.73 +/- 3.78 vs 3.02 +/-
      2.24, p < 0.001). The SUVmax cut-off value for differentiating necks with ECS
      from those without ECS was 3.85. The presence of ECS (p = 0.036) and median
      SUVmax (using 3.85 as a cut-off) (p = 0.037) were found to have a significant
      adverse effect on 5-year disease-specific survival by univariate analysis. The
      multivariate analysis showed a significant association of 5-year disease-specific
      survival with ECS (hazard ratio (HR) = 32.3 in cervical metastasis with ECS, p =
      0.012; and HR = 19.6 in cervical metastasis without ECS, p = 0.024).

PMID- 24032572
TI  - Impact of head and neck malignancies on risk factors and survival in systemic
      lupus erythematosus.
AB  - CONCLUSIONS: Systemic lupus erythematosus (SLE) is associated with an increased
      risk of developing a head and neck malignancy (HNM). A history of SLE did not
      significantly impact the survival of our study cohort after cancer developed.
      OBJECTIVES: To examine the risk and survival rates of HNM in patients with SLE.
      METHODS: This was a population-based, retrospective cohort study. We compared
      patients newly diagnosed with SLE between 2001 and 2008 (n = 8751) with age
      matched controls (1:10) (n = 87 510). The incidence of HNMs at the end of 2009
      was then determined. RESULTS: We found a 2.16-fold higher risk of HNMs in
      patients diagnosed with SLE compared with the risk of first malignancy in the age
      matched controls (incidence rate ratio, IRR = 2.16, p < 0.05). The site with the
      highest incidence of HNMs in SLE patients was the oral cavity (5/11, 45.45%),
      followed by the nasopharynx (4/11, 36.36%). SLE displayed no synergic effect on
      the survival of SLE patients with an HNM compared with age-matched controls with
      a new HNM (p = 0.2446).

PMID- 24032573
TI  - Surgery with postoperative radiotherapy for pN2 head and neck squamous cell
      carcinoma.
AB  - CONCLUSION: Factors that affected prognosis were T stage and extracapsular spread
      in patients that underwent primary surgery with postoperative radiotherapy for
      pN2 head and neck carcinoma. OBJECTIVES: The purpose of this study was to examine
      treatment outcomes and define prognostic factors for pN2 head and neck carcinoma.
      METHODS: A total of 209 patients underwent surgery with postoperative
      radiotherapy between 1994 and 2011. Primary tumor sites were the oropharynx (n =
      70), hypopharynx (n = 48), larynx (n = 47), and oral cavity (n = 44). There were
      21, 83, 60, and 45 patients with stage T1 to T4 cancers, respectively. The N
      stages were 20 N2a, 129 N2b, and 60 N2c. RESULTS: The recurrence rate was 40%
      (83/209) over a mean observation period of 39 months. The 5-year disease-free
      survival (DFS), disease-specific survival (DSS), and overall survival (OS) rates
      in our cohort were 44%, 60%, and 56%, respectively. The presence of advanced T
      stage or extracapsular spread had a significant adverse effect on 5-year DFS,
      DSS, and OS rates according to Kaplan-Meier survival curves. Multivariate Cox
      regression analysis confirmed the significant association between 5-year DSS rate
      and advanced T stage (hazard ratio (HR), 2.20; 95% confidence interval (CI), 1.26
      3.82; p = 0.005) and extracapsular spread (HR, 2.29; 95% CI, 1.24-4.21; p =
      0.008).

PMID- 24032574
TI  - A strategy to design efficient fermentation processes for traditional beverages
      production: prickly pear wine.
AB  - This paper describes a methodology to establish an optimal process design for
      prickly pear wine production that preserves the peculiar and unique traits of
      traditional products, generating at the same time, technical information for
      appropriate design of both bioreactor and overall process. The strategy includes
      alcoholic fermentation optimization by the mixed native culture composed by
      Pichia fermentans and Saccharomyces cerevisiae, followed by malolactic
      fermentation optimization by Oenococcus oeni. The optimization criteria were
      based on multiple output functions: alcohol content, volatile compounds profile,
      organic acids profile, and compound contents related to color, which were
      analyzed by spectroscopy-chromatography methods and sensory analysis. The results
      showed that the mixed culture inoculated into a bioreactor containing prickly
      pear juice with 20  degrees Bx of fermentable sugars concentration, processed at
      a constant temperature of 20  degrees C for 240 h, leads to a fermented product
      with 9.93% (v/v) total alcohol content, and significant abundance of volatile
      compounds, which provide fruity and ethereal aromatic notes, complemented by a
      lively but not unpleasant acidity. This young wine was further subjected to
      malolactic fermentation at constant temperature (16  degrees C) for 192 h,
      decreasing malic acid, and balancing volatile compounds contents, thus resulting
      in a product with better aroma and flavor perception, and a velvety feeling of
      long aftertaste. Repeated assays showed that the process is stable, predictable,
      controllable, and reproducible. These results were used for process design and
      spreadsheet construction in order to simulate the process, and properly select
      and size the equipment required for such process. 

PMID- 24032575
TI  - Expedient and versatile formation of novel amino-deoxy-ketoheptuloses.
AB  - Novel monoketoheptuloses have been synthesized employing an amination step in a
      pre- and/or post-C1 chain elongation using a Petasis reagent by starting from
      aldohexoses or aldohexosamines. A series of gluco and manno configured 1-/3-deoxy
      1-/3-amino-ketohept-2-uloses could be obtained. 

PMID- 24032576
TI  - Roflumilast : the new orally active, selective phophodiesterase-4 inhibitor, for
      the treatment of COPD.
AB  - INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a progressive
      disease, the clinical course of which is punctuated by acute exacerbations. While
      long-acting bronchodilators and inhaled corticosteroids can reduce exacerbations,
      some patients do not respond adequately to these agents. Roflumilast , a novel
      orally active, once-daily phophodiesterase-4-selective inhibitor with anti
      inflammatory properties, has been shown to reduce exacerbations and has been
      approved for the treatment of the subset of COPD patients with symptoms of
      chronic cough and sputum who have a history of exacerbations. AREAS COVERED: This
      article describes the pre-clinical and clinical pharmacology of roflumilast and
      analytically reviews the published data from the most relevant Phase-II and -III
      clinical trials evaluating its efficacy and safety. EXPERT OPINION: Roflumilast
      is the first drug specifically targeted to a particular subset of the
      heterogeneous population of COPD patients, namely those with chronic bronchitis
      in addition to severe airflow obstruction and an exacerbation history. Its
      efficacy in reducing exacerbations in patients already receiving a LABA or
      anticholinergic bronchodilator underscores its potential utility as an add-on
      agent in patients who continue to experience exacerbations despite treatment with
      other agents. Adverse events include gastrointestinal side effects, most
      commonly, as well as unexplained weight loss.

PMID- 24032577
TI  - Plasma apelin levels, blood pressure and cardiovascular risk factors in a coastal
      Chinese population.
AB  - OBJECTIVES: To describe the relationship of plasma apelin levels with blood
      pressure in a coastal Chinese population. METHODS: This cross-sectional study
      included a total of 1031 subjects from the coastal areas of China. One-way
      analysis of variance (ANOVA) and linear trend test, Pearson's correlation
      analysis, as well as multivariate linear regression analysis were used to
      evaluate the association between plasma apelin levels and blood pressure.
      RESULTS: Plasma apelin levels dropped with increasing quartiles of systolic blood
      pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure
      (MABP) (all P<0.001). SBP, DBP, and MABP values decreased as the apelin levels
      increased within the quartiles. After adjusting for age and gender, the
      significant differences in SBP, DBP, and MABP between the groups within the
      apelin quartiles remained (all P<0.05). A significant negative correlation
      between SBP, DBP, as well as MABP and apelin levels was observed (all P<0.01);
      even after adjusting for cardiovascular confounding factors, this negative
      correlation remained (all P<0.001). CONCLUSION: A negative correlation between
      plasma apelin levels and blood pressure was found in this 1000-population-based
      epidemiological study. Apelin may become a potential therapeutic target of anti
      hypertensive treatment.

PMID- 24032578
TI  - Microsurgical management of acute traumatic injuries of the hand and fingers.
AB  - Traumatic injuries of the hand and fingers may be devastating and can result in
      irreversible functional and psychological problems in individuals who sustain
      them. They occur in all age groups, ranging from the elderly to young children.
      The management of these injuries can be challenging and onerous. As a result, it
      is imperative that the surgeon be both knowledgeable and meticulous in order to
      afford the best possible outcomes. This review focuses on the anatomy, initial
      evaluation, and acute management of these injuries. A variety of treatment
      algorithms are discussed as well, including primary closure, grafting, commonly
      utilized flaps, and replantation. 

PMID- 24032579
TI  - Polydactyly: a review.
AB  - Polydactyly of the hand is a difficult problem and poses a unique challenge for
      the hand surgeon. The embryology of limb development is complex, leading to a
      host of different phenotypes of polydactyly. Polydactyly can occur in any digit
      and is described as preaxial, postaxial, and central, based on location.
      Classification systems exist for each of these locations, which guide treatment
      options. Surgical treatment needs to address the aesthetic and functional aspect
      of hand reconstruction. Careful consideration and planning of surgical treatment
      individualized to each patient is required to obtain the best possible outcome.

PMID- 24032580
TI  - The rise of the metal elbow.
AB  - Painful arthritis of the elbow joint has long been a challenging problem. Elbow
      arthroplasty has emerged as viable treatment method for many patients. Implant
      design and surgical technique have evolved to provide more predict-able symptom
      relief without compromising function. Elbow arthroplasty can now be used to treat
      a wide variety of conditions, including osteoarthritis, rheumatoid arthritis, and
      fractures. This review article presents historical and contemporary perspectives
      on elbow arthroplasty. A thorough discussion of implant design, surgical
      technique, and clinical outcomes is presented. 

PMID- 24032581
TI  - Upper extremity golf injuries.
AB  - Golf is a global sport enjoyed by an estimated 60 million people around the
      world. Despite the common misconception that the risk of injury during the play
      of golf is minimal, golfers are subject to a myriad of potential pathologies.
      While the majority of injuries in golf are attributable to overuse, acute
      traumatic injuries can also occur. As the body's direct link to the golf club,
      the upper extremities are especially prone to injury. A thorough appreciation of
      the risk factors and patterns of injury will afford accurate diagnosis,
      treatment, and prevention of further injury. 

PMID- 24032582
TI  - Updates in the use of bone grafts in the lumbar spine.
AB  - There has been a rapid increase in the number of lumbar fusion procedures
      performed in the last 10 years. Many of these procedures involve the use of bone
      grafts and specifically bone graft extenders and substitutes. Fusion depends on
      host and surgical factors including the selection of an appropriate graft. Bone
      grafts have osteoconductive, osteoinductive, and osteogenic properties. Iliac
      crest autograft has long been considered the gold standard for bone graft
      procedures as it inherently imparts all three. However, its use is associated
      with significant disadvantages including donor site pain, increased operative
      time, and insufficient availability. Allograft has been used to avoid the
      complications of donor site morbidity but has increased risks of rejection,
      disease transmission, and slower incorporation into the host bone. The use of
      alternative bone grafting options, such as demineralized bone matrix, synthetics
      (ceramics), bone morphogenetic proteins, collagen-based matrices, autogenous
      growth factors, and bone marrow aspirate, have become routine in some
      institutions. This review paper highlights the different bone grafting options
      currently available, discusses their pros and cons, and briefly reviews the
      relevant literature.

PMID- 24032583
TI  - Fusionless surgery for scoliosis.
AB  - Scoliosis is a very common condition, affecting approximately 7 million children
      in the United States. Treatment of this condition in young children can be
      challenging. A variety of techniques that avoid spinal fusion have been developed
      to manage scoliosis in this patient population. This review article describes
      several of these methods, including growing rods, prosthetic ribs, vertebral
      stapling, and vertebral tethering. Particular attention is given to literature
      discussing each technique. 

PMID- 24032584
TI  - Platelet rich placebo? Evidence for platelet rich plasma in the treatment of
      tendinopathy and augmentation of tendon repair.
AB  - Platelet rich plasma (PRP), an autologous sample of blood with a platelet
      concentration above baseline values, is hypothesized to augment soft tissue
      healing. Its use in sports medicine has risen dramatically, with common
      applications including the treatment of refractory tendinopathy and augmenting
      tendon repair. Many commercial preparation systems are available, but the optimal
      preparation remains unknown. Increasing numbers of clinical studies evaluating
      PRP have been reported and have provided both positive and negative evidence for
      its effectiveness. Well-designed, controlled studies are still lacking, but PRP
      may have a benefit for patients with tendinopathy that is refractory to other non
      surgical treatments. Its use in tendon repair is currently not supported.
      Randomized, controlled studies with documentation of platelet, white blood cell,
      and growth factor concentration in the PRP preparation are necessary for future
      comparative research. Use of PRP should be approached judiciously until further
      evidence is available. 

PMID- 24032585
TI  - Osteochondral allografts: applications in treating articular cartilage defects in
      the knee.
AB  - Chondral injury in the knee is a unique challenge to the orthopaedic surgeon.
      Given the high probability of progression to knee arthrosis, the treatment of
      symptomatic cartilage defects of the knee has become an important surgical
      intervention in young, active patients. The demand for an alternative to
      prosthetic resurfacing has driven the trend towards biologic resurfacing and
      joint preservation. Osteochondral allografts are composed of hyaline cartilage
      attached to subchondral bone and are suited for large osteochondral lesions. This
      allograft tissue must be harvested, processed, and stored appropriately to reduce
      the risks of graft failure and potential complications. With appropriate
      indications and surgical techniques, osteochondral allografts have been shown to
      have good long-term graft survival and patient outcomes.

PMID- 24032586
TI  - Total hip arthroplasty periprosthetic femoral fractures: a review of
      classification and current treatment.
AB  - Periprosthetic fractures of the femur after total hip replacement can present
      some unique challenges to the treating reconstructive orthopedic surgeon.
      Treatment may differ depending on fracture location, bone condition, implant
      stability, patient characteristics, and surgeon experience. It is imperative that
      adequate and sufficient mechanical fixation be achieved in the treatment of these
      patients. It is crucial that the treating orthopaedic surgeon have a clear and
      effective treatment plan to manage these complex cases. The patient's final
      outcome is dependent on fracture union, implant stability, early functional
      recovery, and return to pre-injury independence. This review presents an overview
      of the current diagnostic and treatment approaches, with the goal of providing a
      template for optimal decision-making when dealing with these complex injuries. 

PMID- 24032587
TI  - High-performance total knee replacement.
AB  - The concept of a high-performance total knee replacement has gained prominence
      because of continued technological improvements by implant manufacturers and the
      changing expectations of an increasingly younger, more active patient population.
      Improvements in surgical technique, instrumentation, implant design,
      biomaterials, and implant fixation have occurred in recent years. The literature
      is inconclusive whether novel approaches can lead to improvements in patient
      satisfaction rates, address objectively measured parameters, and improve implant
      survival rates, while doing so in a cost-efficient manner. 

PMID- 24032588
TI  - The evolution of the Ilizarov technique: part 1: the history of limb lengthening.
AB  - The history of limb-lengthening surgery can be traced back to the nineteenth
      century. Since that time, the orthopaedic community has made tremendous progress
      in performing successful lengthening procedures. Among the important contributors
      to the field, Dr. Gavril Ilizarov remains one of the most significant innovators.
      Because of advancements over the past century, limb lengthening has become a
      viable method of treating severe bony deformities and defects. This article, the
      first of a two-part series, reviews the history of distraction osteosynthesis. 

PMID- 24032589
TI  - The evolution of the Ilizarov technique: part 2: the principles of distraction
      osteosynthesis.
AB  - The history of limb-lengthening surgery can be traced back to the 19th Century.
      Since that time, the orthopaedic community has made tremendous progress in
      performing successful lengthening procedures. Among the important contributors to
      the field is Dr. Gavril Ilizarov. Because of advancements over the past century,
      limb lengthening has become a viable method of treating severe bony deformities
      and defects. This article, the second of a two-part series, reviews the
      principles of distraction osteosynthesis, including a thorough discussion of
      indications, instrumentation, and surgical technique. 

PMID- 24032590
TI  - Post-traumatic ankle arthritis.
AB  - Post-traumatic ankle arthritis can be a very disabling condition especially in
      young patients. Localization of the pain is important to allow appropriate
      treatment. Non-surgical treatment options include anti-inflammatory medications
      and use of bracing. Multiple surgical options range from joint sparing procedures
      for the younger patient to total ankle replacement for the older, less active
      patient. Arthrodesis remains the gold standard and is the procedure of choice for
      younger patients who are heavy laborers and in patients with severe arthritis who
      are not candidates for a total ankle replacement. Joint sparing operations
      include allograft resurfacing, arthroscopic debridement and osteophyte resection,
      joint distraction arthroplasty, and supramalleolar osteotomy. In older low demand
      patients, the surgeon may consider a total ankle arthroplasty as an alternative
      to arthrodesis. 

PMID- 24032591
TI  - Intracellular poly(I:C) initiated gastric adenocarcinoma cell apoptosis and
      subsequently ameliorated NK cell functions.
AB  - Natural killer (NK) cells are granular lymphocytic cells that exert essential
      functions in viral infection defense and tumor immune surveillance. However, the
      functions of NK cells were impaired in cancer patients. Polycytidylic acid
      [poly(I:C)] has been used as an immune adjuvant to improve innate and adaptive
      immune responses. In this study, intracellular poly(I:C) could trigger gastric
      adenocarcinoma cells apoptosis quickly. Meanwhile, the sensitivity of poly(I:C)
      treated gastric adenocarcinoma cells to NK cell cytolysis was increased,
      concomitant with the elevated expression of MICA/B and Fas. Furthermore, the
      cytolytic activity of NK cells against tumor cells was augmented significantly by
      the supernatant from poly(I:C)-transfected tumor cells compared with NK cells
      treated by the supernatant from untreated tumor cells, as well as the
      proliferation and migration abilities of NK cells. In this process, the
      activating receptors and cytolysis-associated molecules of NK cells were up
      regulated. Further investigation showed that type I interferon (IFN) produced by
      poly(I:C)-transfected gastric adenocarcinoma cells played an important role in
      this process. Our findings demonstrated that intracellular poly(I:C) not only
      triggered gastric adenocarcinoma cell apoptosis, but also enhanced NK responses
      via inducing type I IFN production by gastric adenocarcinoma cells. These
      functions make poly(I:C) a promising therapeutic medicine for gastric
      adenocarcinoma. 

PMID- 24032592
TI  - Studies on the inactivation of human parvovirus 4.
AB  - BACKGROUND: Human parvovirus 4 (PARV4) is a novel parvovirus, which like
      parvovirus B19 (B19V) can be a contaminant of plasma pools used to prepare plasma
      derived medicinal products. Inactivation studies of B19V have shown that it is
      more sensitive to virus inactivation strategies than animal parvoviruses.
      However, inactivation of PARV4 has not yet been specifically addressed. STUDY
      DESIGN AND METHODS: Treatment of parvoviruses by heat or low-pH conditions causes
      externalization of the virus genome. Using nuclease treatment combined with real
      time polymerase chain reaction, the extent of virus DNA externalization was used
      as an indirect measure of the inactivation of PARV4, B19V, and minute virus of
      mice (MVM) by pasteurization of albumin and by low-pH treatment. Infectivity
      studies were performed in parallel for B19V and MVM. RESULTS: PARV4 showed
      greater resistance to pasteurization and low-pH treatment than B19V, although
      PARV4 was not as resistant as MVM. There was a 2- to 3-log reduction of
      encapsidated PARV4 DNA after pasteurization and low-pH treatment. In contrast,
      B19V was effectively inactivated while MVM was stable under these conditions.
      Divalent cations were found to have a stabilizing effect on PARV4 capsids. In the
      absence of divalent cations, even at neutral pH, there was a reduction of PARV4
      titer, an effect not observed for B19V or MVM. CONCLUSION: In the case of heat
      treatment and incubation at low pH, PARV4 shows intermediate resistance when
      compared to B19V and MVM. Divalent cations seem important for stabilizing PARV4
      virus particles.

PMID- 24032593
TI  - Cu-catalyzed esterification reaction via aerobic oxygenation and C-C bond
      cleavage: an approach to alpha-ketoesters.
AB  - The Cu-catalyzed novel aerobic oxidative esterification reaction of 1,3-diones
      for the synthesis of alpha-ketoesters has been developed. This method combines C
      C sigma-bond cleavage, dioxygen activation and oxidative C-H bond
      functionalization, as well as provides a practical, neutral, and mild synthetic
      approach to alpha-ketoesters which are important units in many biologically
      active compounds and useful precursors in a variety of functional group
      transformations. A plausible radical process is proposed on the basis of
      mechanistic studies. 

PMID- 24032594
TI  - Calcified neurocysticercosis lesions and antiepileptic drug-resistant epilepsy: a
      surgically remediable syndrome?
AB  - PURPOSE: In contrast to the well-recognized association between acute symptomatic
      seizures and neurocysticercosis, the association between antiepileptic drug (AED)
      resistant epilepsy and calcified neurocysticercosis lesions (CNLs) is poorly
      understood. We studied the association between AED-resistant epilepsy and CNLs,
      including the feasibility and outcome of resective surgery. METHODS: From the
      prospective database maintained at our epilepsy center, we reviewed the data of
      all patients with AED-resistant epilepsy who underwent presurgical evaluation
      from January 2001 to July 2010 and had CNL on imaging. We used clinical,
      neuroimaging, and interictal, ictal, and intracranial electroencephalography
      (EEG) findings to determine the association between CNL and epilepsy. Suitable
      candidates underwent resective surgery. KEY FINDINGS: Forty-five patients
      fulfilled the inclusion criteria. In 17 patients, CNL was proven to be the
      causative lesion for AED-resistant epilepsy (group 1); in 18 patients, CNL was
      associated with unilateral hippocampal sclerosis (HS; group 2); and in 10
      patients, CNLs were considered as incidental lesions (group 3). In group 1
      patients, CNLs were more common in frontal lobes (12/17), whereas in group 2
      patients, CNLs were more commonly located in temporal lobes (11/18; p = 0.002).
      Group 2 patients were of a younger age at epilepsy onset than those in group 1
      (8.9 +/- 7.3 vs. 12.6 +/- 6.8 years, p = 0.003). Perilesional gliosis was more
      common among patients in group 1 when compared to group 3 patients (12/17 vs.
      1/10; p = 0.006). Fifteen patients underwent resective surgery. Among group 1
      patients, four of five became seizure-free following lesionectomy alone. In group
      2, four patients underwent anterior temporal lobectomy (ATL) alone, of whom one
      became seizure-free; five underwent ATL combined with removal of CNL (two of them
      after intracranial EEG and all of them became seizure-free, whereas one patient
      underwent lesionectomy alone and did not become seizure-free. SIGNIFICANCE: In
      endemic regions, although rare, CNLs are potential cause for AED-resistant and
      surgically remediable epilepsy, as well as dual pathology. Presence of
      perilesional gliosis contributes to epileptogenicity of these lesions. For those
      patients with CNL and HS, resection of both lesions favors better chance of
      seizure-free outcome.

PMID- 24032595
TI  - Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis
      through interaction with misfolded superoxide dismutase 1.
AB  - Although the aberrant assembly of mutant superoxide dismutase 1 (mSOD1) is
      implicated in the pathogenesis of familial amyotrophic lateral sclerosis (ALS),
      the molecular basis of superoxide dismutase 1 (SOD1) oligomerization remains
      undetermined. We investigated the roles of transglutaminase 2 (TG2), an
      endogenous cross-linker in mSOD1-linked ALS. TG2 interacted preferentially with
      mSOD1 and promoted its oligomerization in transfected cells. Purified TG2
      directly oligomerized recombinant mutant SOD1 and the apo-form of the wild-type
      SOD1 proteins in a calcium-dependent manner, indicating that misfolded SOD1 is a
      substrate of TG2. Moreover, the non-cell-autonomous effect of extracellular TG2
      on the neuroinflammation was suggested, since the TG2-mediated soluble SOD1
      oligomers induced tumor necrosis factor-alpha, interleukin-1beta, and nitric
      oxide in microglial BV2 cells. TG2 was up-regulated in the spinal cord of pre
      symptomatic G93A SOD1 transgenic mice and in the hypoglossal nuclei of mice
      suffering nerve ligation. Furthermore, inhibition of spinal TG2 by cystamine
      significantly delayed the progression and reduced SOD1 oligomers and microglial
      activation. These results indicate a novel role of TG2 in SOD1 oligomer-mediated
      neuroinflammation, as well as in the involvement in the intracellular aggregation
      of misfolded SOD1 in ALS.

PMID- 24032596
TI  - Characteristics and evaluation of an injectable clarithromycin lipid-based
      complex in vitro and in vivo.
AB  - The purpose of this paper is to prepare a less-irritating and lipid-based
      clarithromycin complex (LCC) by the route of intravenous administration qualified
      with high drug-loading and fine particle size. The LCC was prepared by the
      injection of organic solvent phase (containing clarithromycin, sodium cholesterol
      sulfate and phospholipid at a molar ratio of 1:1:1.5) into the Tris buffer
      solution (0.05 M, pH 7.2) at 40  degrees C, and then was concentrated by
      ultrafiltration to remove the organic solvent. The technique of lyophilization
      was applied to obtain the LCC lyophilized products. Evaluation of the injectable
      LCC was performed by particle sizes analysis, transmission electron microscope,
      entrapment efficiency, stability and irritation tests. The LCC possessed a log
      normal size distribution with an average size of 75.4 nm. The drug entrapment
      efficiency was above 97.0%, which was influenced by the amount of phospholipid,
      pH value of the media and ionic strength of aqueous suspension. The results of
      stability and irritation tests proved that LCC had more stability and less
      irritation. This unique LCC formulation may be applied to the human by the route
      of injection with less or no irritation. LCC could be an appropriate candidate
      for intravenous preparation and has a great potential for clinical and industrial
      scale production.

PMID- 24032598
TI  - Long-term result and patient reported outcome of wrist splint treatment for
      carpal tunnel syndrome.
AB  - Carpal tunnel syndrome (CTS) is the commonest peripheral neuropathy presenting to
      specialist hand and wrist clinics. This study investigated the long-term outcome
      of carpal tunnel syndrome treated with isolated night wrist splint and the
      factors determining the likelihood of success of this intervention. Seventy-five
      patients referred to a specialist hand clinic with CTS were given night wrist
      splint treatment for 3 months as per a previous study protocol. Fifty-two
      patients from this cohort did not wish to have surgery after wrist splint
      treatment and were followed for a further 33-month period. Baseline pain and
      numbness levels were recorded on a Visual Analogue Scale (VAS) using a
      questionnaire upon first presentation. A further questionnaire at 36 months
      reassessed pain and numbness levels, patients' satisfaction with the treatment,
      and whether they had subsequent surgical decompression. Of the patients who
      completed the follow-up questionnaire 33 months after their period of
      conservative management, 43% were successfully treated with splint treatment
      alone. There was no difference in the VAS for pain or numbness at the baseline
      and at 36 months between successful and failed treatment groups. Patients
      successfully treated with wrist splinting alone reported a higher level of
      satisfaction with their treatment compared to patients who failed wrist splint
      treatment or had surgical decompression. The results reinforce the previous
      recommendation on wrist splinting as a first-line treatment in the Primary Care
      setting. Referral to specialist hand and wrist clinics should be reserved for
      patients with symptoms refractory to this initial measure.

PMID- 24032597
TI  - Interleukin-1beta triggers the differentiation of macrophages with enhanced
      capacity to present mycobacterial antigen to T cells.
AB  - The rapid differentiation of monocytes into macrophages (MPhi) and dendritic
      cells is a pivotal aspect of the innate immune response. Differentiation is
      triggered following recognition of microbial ligands that activate pattern
      recognition receptors or directly by pro-inflammatory cytokines. We demonstrate
      that interleukin-1beta (IL-1beta) induces the rapid differentiation of monocytes
      into CD209(+) MPhi, similar to activation via Toll-like receptor 2/1, but with
      distinct phenotypic and functional characteristics. The IL-1beta induced MPhi
      express higher levels of key markers of phagocytosis, including the Fc-receptors
      CD16 and CD64, as well as CD36, CD163 and CD206. In addition, IL-1beta-induced
      MPhi exert potent phagocytic activity towards inert particles, oxidized low
      density lipoprotein and mycobacteria. Furthermore, IL-1beta-induced MPhi express
      higher levels of HLA-DR and effectively present mycobacterial antigens to T
      cells. Therefore, the ability of IL-1beta to induce monocyte differentiation into
      MPhi with both phagocytosis and antigen-presenting function is a distinct part of
      the innate immune response in host defence against microbial infection.

PMID- 24032599
TI  - Radiotherapy for lentigo maligna: a literature review and recommendations for
      treatment.
AB  - Lentigo maligna (LM) incidence is increasing. LM frequently involves the face
      near critical anatomical structures and as a consequence clinical management is
      challenging. Nonsurgical therapies, including radiotherapy (RT), are increasingly
      used. Evidenced-based treatment guidelines are lacking. We conducted a review of
      previously published data analysing RT treatment of LM. A search of PubMed,
      Embase and Medline databases to June 2012 identified nine clinical studies that
      examined the use of RT for LM treatment in at least five patients. Nine studies
      described 537 patients with LM treated with definitive primary RT, between 1941
      and 2009, with a median reported follow-up time of 3 years. Eight articles could
      be reviewed for oncological outcome data. There were 18 recurrences documented in
      a total of 349 assessable patients (5%). Salvage was successful in the majority
      of recurrent LM cases by using further RT, surgery or other therapies.
      Progression to LM melanoma (LMM) occurred in five patients (five out of 349,
      1.4%) who all had poor outcomes. There were five marginal recurrences documented
      out of 123 assessable patients (4%). There were eight in-field recurrences
      documented with either LM (five) or LMM (three) out of 171 assessable patients
      (5%). A series of recommendations were then developed for RT parameters for
      treatment of LM. These parameters include treatment volume, dose, dose per
      fraction and outcome measures. These may be of use in prospective data
      collection.

PMID- 24032602
TI  - A generic simulation model for planning critical care resource requirements.
AB  - Intensive care capacity planning based on factual or forecasted mean admission
      numbers and mean length of stay without taking non-linearity and variability into
      account is fraught with error. Simulation modelling may allow for a more accurate
      assessment of capacity needs. We developed a generic intensive care simulation
      model using data generated from anonymised patient records of all admissions to
      four different hospital intensive care units. The model was modified and
      calibrated stepwise to identify important parameters and their values to obtain a
      match between model predictions and actual data. The most important
      characteristic of the final model was the dependency of admission rate on actual
      occupancy. Occupancy, coverage and transfers of the final model were found to be
      within 2% of the actual data for all four simulated intensive care units. We have
      shown that this model could provide accurate decision support for planning
      critical care resource requirements. 

PMID- 24032600
TI  - Rasburicase in the prevention of laboratory/clinical tumour lysis syndrome in
      children with advanced mature B-NHL: a Children's Oncology Group Report.
AB  - Laboratory (LTLS) and clinical (CTLS) tumour lysis syndrome (TLS) are frequent
      complications in newly diagnosed children with advanced mature B cell non-Hodgkin
      lymphoma (B-NHL). Rasburicase, compared to allopurinol, results in more rapid
      reduction of uric acid in paediatric patients at risk for TLS. However, the
      safety and efficacy of rasburicase for the treatment or or prevention of TLS has
      not been prospectively evaluated. Children with newly diagnosed stage III-IV,
      bone marrow(+) and/or central nervous system(+) mature B-NHL received hydration
      and rasburicase prior to cytoreductive therapy. Rasburicase was safe and well
      tolerated and there were no grade III-IV toxicities probably or directly related
      to rasburicase. Patients with an initial lactate dehydrogenase >=2* upper limit
      of normal had a significantly elevated uric acid level (P = 0.005), increased
      incidence of TLS (P-0.005) and lower glomerular filtration rate (GFR; P < 0.001).
      Following rasburicase, there was only a 9% and 5% incidence of LTLS and CTLS,
      respectively. Furthermore, there was a significant improvement in estimated GFR
      from Day 0 to Day 7 following rasburicase (P = 0.0007) and only 1.3% of patients
      required new onset renal assisted support after rasburicase administration. A TLS
      strategy incorporating rasburicase prior to cytoreductive chemotherapy proved
      safe and effective in preventing new onset renal failure and was associated with
      a significant improvement in GFR. 

PMID- 24032603
TI  - Hypermethylation of HOXA10 gene in mid-luteal endometrium from women with ovarian
      endometriomas.
AB  - A decrease in HOXA10 gene expression in eutopic mid-secretory endometrium has
      been found in women with endometriosis-associated infertility. Promoter
      hypermethylation of HOXA10 is thought to be the leading mechanism for epigenetic
      gene regulation in patients with endometriosis. In our series we documented
      significantly higher HOXA10 promoter methylation levels in women with ovarian
      endometriomas than in healthy controls during the mid-luteal phase. Development
      of epigenetic-based strategies for non-surgical treatment of infertility related
      to ovarian endometriomas could be an attractive field of research in the coming
      years. 

PMID- 24032601
TI  - Targeting hexokinase II to mitochondria to modulate energy metabolism and reduce
      ischaemia-reperfusion injury in heart.
AB  - Mitochondrially bound hexokinase II (mtHKII) has long been known to confer cancer
      cells with their resilience against cell death. More recently, mtHKII has emerged
      as a powerful protector against cardiac cell death. mtHKII protects against
      ischaemia-reperfusion (IR) injury in skeletal muscle and heart, attenuates
      cardiac hypertrophy and remodelling, and is one of the major end-effectors
      through which ischaemic preconditioning protects against myocardial IR injury.
      Mechanisms of mtHKII cardioprotection against reperfusion injury entail the
      maintenance of regulated outer mitochondrial membrane (OMM) permeability during
      ischaemia and reperfusion resulting in stabilization of mitochondrial membrane
      potential, the prevention of OMM breakage and cytochrome C release, and reduced
      reactive oxygen species production. Increasing mtHK may also have important
      metabolic consequences, such as improvement of glucose-induced insulin release,
      prevention of acidosis through enhanced coupling of glycolysis and glucose
      oxidation, and inhibition of fatty acid oxidation. Deficiencies in expression and
      distorted cellular signalling of HKII may contribute to the altered sensitivity
      of diabetes to cardiac ischaemic diseases. The interaction of HKII with the
      mitochondrion constitutes a powerful endogenous molecular mechanism to protect
      against cell death in almost all cell types examined (neurons, tumours, kidney,
      lung, skeletal muscle, heart). The challenge now is to harness mtHKII in the
      treatment of infarction, stroke, elective surgery and transplantation. Remote
      ischaemic preconditioning, metformin administration and miR-155/miR-144
      manipulations are potential means of doing just that.

PMID- 24032605
TI  - Controlling the physical and biological properties of highly fluorescent aqueous
      quantum dots using block copolymers of different size and shape.
AB  - The phase transfer of fluorescent CdSe based quantum dots (QDs) while retaining
      their properties and offering some advantages concerning the stability and
      functionalization characteristics is an important and intensively investigated
      field of research. Here we report how to tune and control the properties of
      CdSe/CdS/ZnS core-shell-shell QDs in water, using poly(isoprene-block-ethylene
      oxide) (PI-b-PEO) as a versatile system of amphiphilic diblock copolymers for the
      micellular encapsulation of nanoparticles (NPs). We show the synthesis of a novel
      PI-b-(PEO)2 miktoarm star polymer and how this different architecture besides the
      variation of the polymers' molecular weight gives us the opportunity to control
      the size of the built constructs in water between 24 and 53 nm. Because of this
      size control, an upper limit of the construct's diameter for the cellular uptake
      could be determined by a systemic study with human alveolar epithelial cells
      (A549) and murine macrophage leukemia cell (RAW-264.7). Furthermore, fluorescence
      quenching experiments with copper(II) and iron(III) ions show a strong influence
      of the used polymer on the shielding against these ions. This enables us to
      control the permeability of the polymer shell from very porous shells, which
      allow an almost complete cation exchange up to very dense shells. These even
      offer the possibility to perform copper(I) catalyzed click reactions while
      keeping the fluorescence of the QDs. All these results underline the huge
      variability and controllability of the PI-b-PEO diblock copolymer system for the
      encapsulation and functionalization of nanoparticles for biological applications.
      As a general trend, it can be stated that those coatings, which were most stable
      against quenchers, also showed the best resistivity with respect to unspecific
      cellular uptake. 

PMID- 24032604
TI  - Triiodothyronine and free thyroxine levels are differentially associated with
      metabolic profile and adiposity-related cardiovascular risk markers in euthyroid
      middle-aged subjects.
AB  - BACKGROUND: We have previously shown that in healthy young men, a less favorable
      body composition is associated with higher free triiodothyronine (fT3) levels
      within the euthyroid range. Besides, a higher free-triiodothyronine-to-free
      thyroxin (fT3-to-fT4) ratio has been related to a less favorable metabolic
      phenotype and more placental growth in pregnant women. In the present study, we
      therefore investigated whether serum thyrotropin (TSH), thyroid hormone levels,
      and the fT3-to-fT4 ratio are associated with metabolic and adiposity-related
      cardiovascular risk markers in a healthy population of middle-aged euthyroid men
      and women. METHODS: Thyroid parameters were measured in 2524 generally healthy
      subjects from the Asklepios Study (35-55 years, mean age 46 years). Analyses were
      restricted to 2315 subjects (1138 women and 1177 men), not using thyroid
      medication, not having anti-TPO levels above clinical cutoff values or TSH levels
      outside the reference range (0.27-4.2 mU/L). Twenty-seven percent of the women
      and 47.5% of the men were overweight, while 13% of women and 17% of men were
      obese. Twenty percent of the subjects were active smokers. Serum thyroid function
      parameters were determined by electrochemiluminescence. RESULTS: fT3 and the fT3
      to-fT4 ratio were positively related to body mass index (BMI), waist
      circumference, and components of metabolic syndrome, that is, triglycerides,
      systolic and diastolic blood pressure, and fasting plasma glucose, and negatively
      with HDL-cholesterol levels, whereas fT4 was negatively associated with BMI,
      waist circumference, and triglycerides (p<0.001). TSH related positively with
      total cholesterol levels (p<0.01), triglycerides, and systolic and diastolic
      blood pressure (p<0.001). The fT3-to-fT4 ratio was further positively associated
      with the adiposity-related inflammation markers interleukin-6 and high
      sensitivity C-reactive protein and to pulse wave velocity. All associations were
      adjusted for sex, age, height, and smoking, and most associations persisted after
      additional adjustment for weight or waist circumference. CONCLUSION: In healthy
      euthyroid middle-aged men and women, higher fT3 levels, lower fT4 levels, and
      thus a higher fT3-to-fT4 ratio are consistently associated with various markers
      of unfavorable metabolic profile and cardiovascular risk.

PMID- 24032606
TI  - Adsorptive removal of patulin from apple juice using Ca-alginate-activated carbon
      beads.
AB  - This study aimed to investigate the adsorption of patulin from apple juice by Ca
      alginate-activated carbon (Ca-alginate-AC) beads. The capacity of patulin was
      determined by high-performance liquid chromatography. The results showed that Ca
      alginate-AC beads have significant ability to reduce patulin from contaminated
      apple juice. Furthermore, the adsorption process did not affect the quality of
      apple juice. The effects of contact time, initial patulin concentration,
      adsorbent dose, and temperature were assessed. The removal percentage of patulin
      increased with contact time, adsorbent dose, and temperature. A reduction was
      also noted to bind patulin at increased levels of contamination. The equilibrium
      data were fitted to Langmuir, Freundlich, and Temkin isotherm models and the
      isotherm constants were calculated at different temperatures. The adsorption
      equilibrium was best described by the Freundlich isotherm (R(2) > 0.990). The
      pseudo 1st-order model was found to describe the kinetic data satisfactorily.
      Thermodynamic parameters such as standard Gibbs free energy (DeltaG??), standard
      enthalpy (DeltaH?), and standard entropy (DeltaS?) were evaluated. The results
      showed that the adsorption was spontaneous and endothermic nature. 

PMID- 24032607
TI  - A novel tandem sequence to pyrrole syntheses by 5-endo-dig cyclization of 1,3
      enynes with amines.
AB  - The synthesis of pentasubstituted pyrroles has been described using molecular
      iodine from 1,3-enynes and amines via a sequential tandem aza-Michael addition,
      iodocyclization, and oxidative aromatization. The protocol is simple and
      efficient to afford the target products at ambient conditions. 

PMID- 24032608
TI  - Nucleocapsid of Tomato spotted wilt tospovirus forms mobile particles that
      traffic on an actin/endoplasmic reticulum network driven by myosin XI-K.
AB  - A number of viral proteins from plant viruses, other than movement proteins, have
      been shown to traffic intracellularly along actin filaments and to be involved in
      viral infection. However, there has been no report that a viral capsid protein
      may traffic within a cell by utilizing the actin/endoplasmic reticulum (ER)
      network. We used Tomato spotted wilt tospovirus (TSWV) as a model virus to study
      the cell biological properties of a nucleocapsid (N) protein. We found that TSWV
      N protein was capable of forming highly motile cytoplasmic inclusions that moved
      along the ER and actin network. The disruption of actin filaments by latrunculin
      B, an actin-depolymerizing agent, almost stopped the intracellular movement of N
      inclusions, whereas treatment with a microtubule-depolymerizing reagent,
      oryzalin, did not. The over-expression of a myosin XI-K tail, functioning in a
      dominant-negative manner, completely halted the movement of N inclusions.
      Latrunculin B treatment strongly inhibited the formation of TSWV local lesions in
      Nicotiana tabacum cv Samsun NN and delayed systemic infection in N. benthamiana.
      Collectively, our findings provide the first evidence that the capsid protein of
      a plant virus has the novel property of intracellular trafficking. The findings
      add capsid protein as a new class of viral protein that traffics on the actin/ER
      system. 

PMID- 24032610
TI  - RAPID3, an index of only 3 patient self-report core data set measures, but not
      ESR, recognizes incomplete responses to methotrexate in usual care of patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To perform a longitudinal cohort study concerning the capacity of
      prospectively-collected erythrocyte sedimentation rates (ESR) and scores for
      physical function, pain, patient global estimate, and routine assessment of
      patient index data (RAPID3) on a multidimensional health assessment questionnaire
      (MDHAQ), to recognize incomplete versus adequate responses to methotrexate in
      rheumatoid arthritis (RA) in one usual care setting, prior to description of
      RAPID3. METHODS: All patients were seen in one academic setting, in which MDHAQ
      scores were collected in all patients at all visits in the infrastructure of
      care. ESR was collected in all RA patients. All 93 RA patients in whom
      methotrexate was initiated between 1996 and 2001 with available 5-year follow-up
      were analyzed. "Incomplete response" was defined as initiation of subsequent
      biological therapy and "adequate response" as no biological therapy over 5 years.
      Measures were analyzed at the baseline methotrexate visit and at a subsequent
      visit: in 30 "incomplete responders" when biological therapy was prescribed; and
      in 63 "adequate responders 2.6 years after methotrexate initiation (mean interval
      to biological therapy in "incomplete responders"). RESULTS: ESR fell similarly by
      33% to 36% in both groups. MDHAQ scores fell by 56% to 79% over 2.6 years in
      adequate responders but increased by 0% to 31% in incomplete responders. Median
      RAPID3 fell from 10.6 to 3.6 (low severity=3.1 to 6, remission<=3) in adequate
      responders and rose from 14.9 to 16.2 (high severity>12) in incomplete
      responders. CONCLUSION: RAPID3, but not ESR, recognizes incomplete versus
      adequate methotrexate responses in usual clinical care, and may be useful in busy
      usual care settings.

PMID- 24032609
TI  - This de-wormed world?

PMID- 24032611
TI  - The urge to prove and its ills.
AB  - The urge to prove rather than the healthy self-critique is much in vogue. This
      trend ranges from our haste in making our research findings public before they go
      through the traditional peer review to almost every domain of our activity as
      physicians and scientists. We seem to be in general content with what we know
      about disease mechanisms, our ability to diagnose, treat, and prevent. I propose
      that this lack of self-critique is also an important component of the less than
      desired status of the physician-drug industry relationship. What is more worrying
      is that the physicians seem to take as the norm that if there is drug industry
      sponsoring in a study the results are always tainted. I propose that "our urge to
      prove" is very much behind this unfortunate state of affairs. I like to think the
      more we stay away from the urge to prove and bring in cerebral activity in the
      direction of self-critique much less likely will the drug industry be able to
      meddle in our affairs. 

PMID- 24032612
TI  - Features and publication rates of scientific abstracts presented at a
      rheumatology congress--EULAR 2008.
AB  - OBJECTIVE: Various types of scientific abstracts are selected and presented at
      meetings and listed in abstract books. Recently, a systematic review has shown
      that 45% of 30,000 abstracts were published in a journal. The aim of this study
      was to determine the features of abstracts selected to be presented at a EULAR
      meeting (2008) and the corresponding publication rates. METHODS: The EULAR 2008
      Abstract Book was extracted, presented abstracts were assessed, their publication
      status was checked, and features related with publication rate were determined.
      The publication status of abstracts as of January 20, 2011, was verified using
      PubMed. RESULTS: A total of 1,732 abstracts were assessed. Median publication
      duration was 13 (range: 0 to 31) months. Most of the abstracts (N=339) were of
      multi-national origin. Sixty seven percent of abstracts were clinical and 563
      (33%) abstracts were preclinical. We found that 601 of all abstracts (34.7%) had
      been published in a journal, and most of were published in a rheumatology
      journal. Fifty-seven percent of published abstracts were in journals with an
      impact factor higher than 4. The publication rate was correlated with
      presentation type, number of centers involved, trial design, and number of
      patients enrolled. CONCLUSIONS: We found that the publication rate of EULAR 2008
      abstracts at 30 months was approximately 35%. This is a high rate compared to a
      previously published systematic review that investigated the publication rate of
      studies initially presented as abstracts in medical meetings, which reported the
      publication rate at 24 and 36 months as 20.7% and 28.1%, respectively. More than
      half of the published abstracts were accepted by high-impact journals.
      Presentation type, number of centers, trial design, and enrolled patient numbers
      were all correlated with the rate of publication.

PMID- 24032613
TI  - A laboratory comparison of a new arthroscopic transosseous rotator cuff repair to
      a double row transosseous equivalent rotator cuff repair using suture anchors.
AB  - BACKGROUND: Because current instrumentation makes it possible to perform an
      arthroscopic transosseous rotator cuff repair, we performed a biomechanical
      comparison of a double-row transosseous equivalent rotator cuff repair using
      suture anchors to an arthroscopic, transosseous rotator cuff repair to determine
      if they provided similar fixation stability. METHODS: Six pairs of shoulders were
      used. One of each pair had a standard double row, transosseous equivalent
      arthroscopic rotator cuff repair using a suture-bridge technique with suture
      anchors, and the other had an arthroscopic transosseous repair using an Xbox
      technique. The repairs were cycled at 150 N for 10,000 cycles with movement of
      the lateral cuff edge recorded and then tested to failure. RESULTS: The total
      cuff edge displacement at 10,000 cycles in the anchor group (transosseous
      equivalent repair) was 7.9 mm and 6.3 mm for the bone tunnel group (transosseous
      repair); these were not significantly different (p=0.19). The anchor group failed
      at an average of 309 N and the bone tunnel group at an average of 339 N (p=0.22).
      DISCUSSION: Biomechanical testing suggests that arthroscopic, transosseous
      rotator cuff repair using a Xbox suture configuration is similar in strength and
      stability to an arthroscopic transosseous equivalent suture-bridge repair. Both
      techniques demonstrated difficulty in maintaining the lateral position of the
      tendon.

PMID- 24032614
TI  - Re-displacement of extraphyseal distal radius fractures following initial
      reduction in skeletally immature patients--can it be prevented?
AB  - PURPOSE: The purpose of this study was to evaluate the efficacy of sugar tongs
      splints to maintain reduction of pediatric distal radius and distal both bones
      forearm fractures compared to acute casting. MATERIALS AND METHODS: The trauma
      database of an urban level-one trauma center was queried for skeletally immature
      patients who had sustained a displaced extraphyseal distal radius fracture.
      Inclusion criteria included: complete radiographs, skeletal immaturity, and
      presence of a displaced fracture of the radius within the metaphyseal segment,
      proximal to the distal radial physis, with or without an associated ulna
      fracture. All patients were seen in the emergency department and treated with a
      standardized protocol of closed reduction and immobilization. All radiographs
      were reviewed for initial and residual displacement. Baseline demographic data
      was also collected, including age at time of injury, handedness, and mechanism of
      injury. Need for operative intervention and associated complications were noted.
      All fractures were followed until union. RESULTS: Thirty-three patients were
      treated with closed reduction and immobilization in a sugar tongs splint, 10
      patients were acutely casted, and 2 patients were placed into a short arm volar
      splint. Twenty-five patients who were initially splinted were treated to
      completion without the need for operative intervention. Eight of the patients
      treated with sugar tongs splints (24%) required surgery. Eight patients who were
      initially casted were treated to completion closed. Two of the patients who were
      initially casted (22%) required operative intervention for loss of reduction.
      Both of the patients who were initially immobilized using a volar splint were
      treated to completion without operative intervention. There was no statistically
      significant difference in the need for operative intervention amongst these
      groups. CONCLUSIONS: This study demonstrates that use of closed reduction and
      placement of a sugar tongs splint can effectively maintain reduction of
      extraphyseal distal radius fractures with rates of displacement similar to that
      seen with acute casting.

PMID- 24032615
TI  - Functional outcomes of anterior cruciate ligament reconstruction with tibialis
      anterior allograft.
AB  - BACKGROUND: Allografts offer potential advantages over autografts in anterior
      cruciate ligament reconstruction (ACLR), including the absence of donor site
      morbidity, shorter operative times, improved cosmesis, and easier rehabilitation.
      There is limited and conflicting outcome data for ACLR with tibialis anterior
      allograft. The purpose of this study was to evaluate the functional outcomes of
      ACLR with tibialis anterior allograft. METHODS: We retrospectively evaluated
      primary ACL reconstructions using tibialis anterior allograft between January
      2004 and December 2006. Clinical outcomes were measured by KT-1000 arthrometry,
      and International Knee Documentation Committee (IKDC), Lysholm, and Tegner
      scores. RESULTS: 19 patients were available for follow-up at a mean of 2.7 years
      (range: 2.0 to 3.2). One patient experienced a traumatic re-rupture that required
      revision and another patient was advised to undergo revision reconstruction for a
      failed graft. Based on IKDC and Lysholm scoring, 12 patients (63%) had good or
      excellent results, 4 (21%) patients had fair results, and 3 (16%) patients had
      poor results. The mean side-to-side difference was 2.7 mm (0 to 8.2) and the mean
      decrease in Tegner activity level was 1.4 (0 to 6). CONCLUSION: An alarming
      number of patients demonstrated residual laxity after ACL reconstruction with
      tibialis anterior allograft. We recommend against using tibialis anterior
      allograft as a first choice graft for high demand patients.

PMID- 24032616
TI  - Tibial plateau fractures with and without meniscus tear--results of a
      standardized treatment protocol.
AB  - OBJECTIVES: The purpose of this study was to determine what patient and injury
      factors are associated with the presence of a meniscus tear in tibial plateau
      fractures. We also sought to compare functional outcome, pain scores, and range
      of motion between patient groups with and without meniscal injury. MATERIALS AND
      METHODS: A total of 99 patients with 101 acute tibial plateau fractures were
      included in the study cohort. Patients were divided into two groups: those with
      and without meniscus tears at the time of initial injury. Statistical analysis
      with Student's t-test for continuous variables and chi square test for
      categorical variables was performed to compare those with and without a meniscal
      tear. Logistic regression was performed to identify the variables that predicted
      the presence of a meniscus tear and repeated ANOVA measures were used to assess
      functional outcome scores. RESULTS: Fifty-four patients with 56 tibial plateau
      fractures (55%) were found to have an associated meniscal tear. The average
      amount of joint depression in this group was 12.3 mm (range: 2.0 to 29.5 mm). The
      remaining 45 patients with 45 fractures (45%) had an average depression of 5.4 mm
      (range: 0.0 to 12.8 mm). Degree of tibial plateau depression was the only
      significant predictor of meniscal injury. CONCLUSIONS: Our findings suggest that
      amount of depression in tibial plateau fractures is a significant predictor of
      the occurrence of a meniscus tear with an odds ratio of 1.36. We also found no
      significant difference in the functional outcome, pain scores, and knee range of
      motion between the group with and without meniscus tears at the longest follow-up
      interval. These findings suggest that acute repair of meniscal injury following
      traumatic fracture of the tibial plateau could produce functional results similar
      to those patients that did not sustain a meniscus tear.

PMID- 24032617
TI  - Erdheim-Chester disease--clinical pathological case discussion.

PMID- 24032618
TI  - Adult onset Still's disease as a paraneoplastic syndrome--a case report and
      review of the literature.
AB  - Adult onset Still's disease (AOSD) is a systemic inflammatory disease with
      unknown etiology and characterized by evanescent salmon pink rash, sore throat,
      liver dysfunction, lymphadenopathy, hepatosplenomegaly, arthritis, and
      leukocytosis. It is a diagnosis of exclusion; however, there are case reports in
      the literature about patients with malignancies and AOSD-like signs and symptoms.
      Here we report a patient with AOSD seems to be associated with sarcomatoid renal
      cell carcinoma. This phenomenon is not distinguishable from primary AOSD either
      in presentation or in treatment; except for the main purpose of the management
      should be targeted to the underlying malignancy. 

PMID- 24032619
TI  - Combined ankle and talus fractures--a case report.
AB  - A 50-year-old male patient sustained a supination-adduction type ankle fracture
      with an associated sagittal split fracture of the talus. The patient was treated
      initially in a short leg splint, and upon presentation to an orthopaedic surgeon,
      an external fixator was applied. After the soft tissue swelling improved enough
      to permit open reduction and internal fixation, the patient was brought back to
      the operating room for definitive treatment with removal of the external fixator
      and open reduction and placement of internal fixation. The patient's
      postoperative course was uncomplicated. At the 6-week follow-up visit, he was
      noted to have a radiographic Hawkin's sign in the dome of the talus. At 3 months
      postoperatively, he was weightbearing as tolerated with radiographic evidence of
      fracture healing, and his ankle range of motion was from 30 degrees  of plantar
      flexion to 15 degrees  of dorsiflexion. At 6 months postoperatively, the patient
      had no complaints and was ambulating in a regular shoe. His plantar flexion was
      35 degrees  and his dorsiflexion was 15 degrees . His subtalar motion was from 5
      degrees  of eversion to 10 degrees  of inversion. He returned for his one-year
      follow-up doing well without complaints, and he had returned to his previous
      activities. 

PMID- 24032620
TI  - Multiple nerve injuries following repair of a distal biceps tendon rupture--case
      report and review of the literature.
AB  - Current repair of a distal biceps tendon rupture has reverted to the single
      incision technique. Postoperative complications are rare, but the most common are
      due to neuropraxia. We present the case of patient who sustained multiple nerve
      injuries following distal biceps repair. This case is presented with a review of
      the literature. 

PMID- 24032621
TI  - Extra-articular knee lesion with high fluorodeoxyglucose-uptake on positron
      emission tomography.
AB  - Pigmented villonodular synovitis (PVNS) is an uncommon musculoskeletal tumor that
      is typically benign and often diagnosed radiologically by magnetic resonance
      imaging (MRI). Fluorodeoxyglucose (FDG)-uptake positron emission tomography (PET)
      is an imaging tool primarily used in oncology to evaluate malignancy. FDG
      measures metabolic activity with standardized uptake value (SUV). A high SUV is
      suggestive of malignancy. We report a case of PVNS detected incidentally by FDG
      PET as an extracapsular mass adherent to vastus medialis tendon with a high SUV
      of 15.1. Given the patient's history of cancer and the high SUV, the lesion was
      initially considered a malignancy. The objective of this case report is to
      illustrate that even a high-SUV mass detected with PET imaging does not
      necessarily indicate malignancy, and thus a benign lesion can also demonstrate
      such elevated signal. 

PMID- 24032622
TI  - Blood system changes since recognition of transfusion-associated AIDS.

PMID- 24032623
TI  - Resveratrol derivatives: a patent review (2009 - 2012).
AB  - INTRODUCTION: There is currently a wealth of information on the effects of
      resveratrol and its derivatives in therapeutic, cosmetic and nutraceutical patent
      applications. Structure-activity studies of the resveratrol scaffold provide a
      foundation for the development of new analogs with potent activity or other
      beneficial properties. Ongoing research has yielded promising results and
      potential use in the treatment of various diseases. AREAS COVERED: This review
      provides analysis of patents published from January 2009 to April 2013. There is
      a focus on different approaches for the production of resveratrol derivatives,
      combinations of new derivatives with old drugs, and applications in therapeutic
      areas, nutraceutical compositions and cosmetics. EXPERT OPINION: The ability of
      resveratrol to interact with a disparate array of subcellular targets is uncanny.
      Nonetheless, even though limited or no toxicity is apparent, the molecule is not
      a panacea due to lack of potency and issues with bioavailability. Thus, as
      witnessed by a number of patents, a large assortment of derivatives have been
      synthesized under the guise of having superior characteristics for treating or
      preventing various diseases or for use as neutraceutics and cosmetics. Some of
      these suppositions are probably correct, but evidence-based applications are
      essentially nil due to a lack of commitment in terms of investing the resources
      necessary for the conduct of obligatory clinical trials. Current usage is largely
      based on anecdotes and publicity. Hopefully, at some point in time, it will be
      possible to follow a standard protocol with a predicable outcome.

PMID- 24032624
TI  - Autonomic neuropathy in HIV is unrecognized and associated with medical
      morbidity.
AB  - Autonomic dysfunction is common in HIV. However, its clinical impact is not well
      understood and its protean symptoms make it difficult to diagnose. We sought to
      determine: (1) whether autonomic neuropathy is associated with morbidity and
      predicted mortality in HIV as measured by the Veterans Aging Cohort Study (VACS)
      index; and (2) if healthcare providers recognize the diagnosis of autonomic
      neuropathy. Data were obtained from 102 HIV-infected adults enrolled in a
      prevalence study of autonomic dysfunction from 2011-2012. Participants were
      predominantly minority with nearly equal numbers of men and women. Most were
      receiving an antiretroviral regimen with a nucleoside reverse transcriptase
      inhibitor backbone and a base of a non-nucleoside reverse transcriptase
      inhibitor, protease inhibitor, or integrase inhibitor. Autonomic neuropathy was
      defined using a laboratory-based autonomic assessment, the Composite Autonomic
      Severity Score (CASS). Medical records were reviewed for the year prior to the
      autonomic assessment. We found that the autonomic neuropathy score (CASS) was
      associated with the VACS index. We also found that among 53 participants with
      symptomatic autonomic neuropathy, the diagnosis had been considered for only one.
      The majority of the symptoms were either unexplained or attributed to medication
      side effects. This study demonstrates that autonomic neuropathy in HIV is
      associated with serious co-morbid illnesses known to increase mortality risk, and
      that HIV healthcare providers rarely consider autonomic neuropathy in their
      differential diagnoses. Future studies are needed to determine if autonomic
      neuropathy is an independent risk factor for mortality in HIV, and to raise
      awareness of its signs and symptoms.

PMID- 24032625
TI  - HIV medication adherence and HIV symptom severity: the roles of sleep quality and
      memory.
AB  - The purpose of the current study was to examine the extent to which self-reported
      sleep quality, a clinically malleable factor, is associated with both HIV
      medication adherence and self-reported HIV symptom severity. In addition, we
      sought to examine whether sleep quality may explain the association between HIV
      medication adherence and symptom severity, as well as the role of self-reported
      memory functioning in terms of the above relations. This study took place from
      April 2010 to March 2012. Participants were 129 HIV-positive individuals who
      completed an ART pill count and series of structured clinical interviews and self
      report questionnaires on sleep, memory, and HIV symptom severity. A series of
      regressions were conducted to test study hypotheses. After accounting for
      covariates (i.e., problematic alcohol, nicotine, and cannabis use, and mood
      disorder diagnosis), results indicated that self-reported sleep quality was
      associated with HIV medication adherence and self-reported HIV symptom severity,
      and that sleep quality partially mediated the relation between medication
      adherence and self-reported HIV symptom severity. In addition, memory functioning
      moderated the relation between self-reported sleep quality and HIV symptom
      severity, such that the interaction of poor sleep quality and relatively good
      memory functioning was associated with heightened self-reported HIV symptom
      severity. This study highlights the importance of assessing sleep and memory
      among HIV-infected individuals as they may represent treatment targets for those
      experiencing poor medication adherence or particularly severe HIV symptoms. Such
      information could lead to the inclusion of adjunct brief interventions to target
      sleep and memory functioning in order to reduce symptom severity among HIV
      positive individuals with poor medication adherence.

PMID- 24032626
TI  - Cost-effectiveness of telaprevir in combination with pegylated interferon alpha
      and ribavirin in treatment-experienced chronic hepatitis C genotype 1 patients.
AB  - BACKGROUND: Telaprevir (TVR,T) and boceprevir (BOC,B) are direct-acting
      antivirals (DAAs) used for the treatment of chronic genotype 1 hepatitis C virus
      (HCV) infection. This analysis evaluated the cost-effectiveness of TVR combined
      with pegylated interferon (Peg-IFN) alfa-2a plus ribavirin (RBV) compared with
      Peg-IFN alfa-2a and RBV (PR) alone or BOC plus Peg-IFN alfa-2b and RBV in
      treatment-experienced patients. METHODS: A Markov cohort model of chronic
      genotype 1 HCV disease progression reflected the pathway of experienced patients
      retreated with DAA therapy. The population was stratified by previous response to
      treatment (i.e., previous relapsers, partial responders, and null responders).
      Sustained virologic response (SVR) rates were derived from a mixed-treatment
      comparison that included results from separate Phase III trials of TVR and BOC.
      Incremental cost per life year (LY) gained and quality-adjusted-life-year (QALY)
      gained were computed at lifetime, adopting the NHS perspective. Costs and health
      outcomes were discounted at 3.5%. Uncertainty was assessed using deterministic
      and probabilistic sensitivity analyses. Sub-group analyses were carried out by
      interleukin (IL)-28B genotype. RESULTS: Higher costs and improved outcomes were
      associated with T/PR relative to PR alone for all experienced patients (ICER of
      L6079). T/PR was cost-effective for each sub-group population with high SVR
      advantage in relapsers (ICER of L2658 vs L7593 and L20,875 for partial and null
      responders). T/PR remained cost-effective regardless of IL-28B sub-type. Compared
      to B/PR, T/PR prolonged QALYs by 0.57 and reduced lifetime costs by L13,960 for
      relapsers. For partial responders T/PR was less costly but less efficacious than
      B/PR, equating to an ICER of L128,117 per QALY gained. LIMITATIONS: No head-to
      head trial provides direct evidence of better efficacy of T/PR vs B/PR.
      CONCLUSION: T/PR is cost-effective compared with PR alone in experienced patients
      regardless of treatment history and IL-28B genotype. Compared to B/PR, T/PR is
      always cost-saving but only more effective in relapsers.

PMID- 24032627
TI  - Functional and structural brain networks in epilepsy: what have we learned?
AB  - Brain functioning is increasingly seen as a complex interplay of dynamic neural
      systems that rely on the integrity of structural and functional networks. Recent
      studies that have investigated functional and structural networks in epilepsy
      have revealed specific disruptions in connectivity and network topology and,
      consequently, have led to a shift from "focus" to "networks" in modern epilepsy
      research. Disruptions in these networks may be associated with cognitive and
      behavioral impairments often seen in patients with chronic epilepsy. In this
      review, we aim to provide an overview that would introduce the clinical
      neurologist and epileptologist to this new theoretical paradigm. We focus on the
      application of a theory, called "network analysis," to characterize resting-state
      functional and structural networks and discuss current and future clinical
      applications of network analysis in patients with epilepsy. 

PMID- 24032628
TI  - Membrane proteins can have high kinetic stability.
AB  - Approximately 10% of water-soluble proteins are considered kinetically stable
      with unfolding half-lives in the range of weeks to millenia. These proteins only
      rarely sample the unfolded state and may never unfold on their respective
      biological time scales. It is still not known whether membrane proteins can be
      kinetically stable, however. Here we examine the subunit dissociation rate of the
      trimeric membrane enzyme, diacylglycerol kinase, from Escherichia coli as a proxy
      for complete unfolding. We find that dissociation occurs with a half-life of at
      least several weeks, demonstrating that membrane proteins can remain locked in a
      folded state for long periods of time. These results reveal that evolution can
      use kinetic stability to regulate the biological function of membrane proteins,
      as it can for soluble proteins. Moreover, it appears that the generation of
      kinetic stability could be a viable target for membrane protein engineering
      efforts. 

PMID- 24032629
TI  - Natural gum as mucoadhesive controlled release carriers: evaluation of
      cefpodoxime proxetil by D-optimal design technique.
AB  - The present study deals with the development of mucoadhesive controlled release
      tablets of Cefpodoxime Proxetil to increase the gastric residence time and thus
      prolong drug release, reduce dosing frequency and improve oral bioavailability.
      Tablets were prepared using sodium alginate and karaya gum, a natural polymer,
      with a synthetic polymer hydroxypropylmethylcellulose (K100LV) and Karaya gum
      with HPMC K100LV in various ratios to optimize the drug release profile using D
      Optimal technique. Pre- and post-compression parameters of tablets prepared with
      various formulations (S1-S9, C1-C9) were evaluated. The FTIR and DSC studies
      revealed that no physiochemical interaction between excipients and drug. The
      formulation S7 showed prolonged drug release, and the mechanism of drug release
      from the optimized formulation was confirmed using the Korsmeyer-Peppas model to
      be non-Fickian release transport and n value was found 0.605 indicating both
      diffusion and erosion mechanism from these natural gums. The optimized
      formulation showed mucoadhesive strength >35 g. An in vivo study was performed on
      rabbits using an X-ray imaging technique. The radiological evidence suggests that
      the tablets adheres (more than 10 hours) to a rabbit's stomach. No significant
      changes were found in the physical appearance, drug content, mucoadhesive study
      and in vitro dissolution pattern after storage at 40  degrees C/75% relative
      humidity for 3 months.

PMID- 24032630
TI  - Incorporation of CF3-pseudoprolines into peptides: a methodological study.
AB  - The peptide coupling reactions allowing the incorporation of trifluoromethyl
      substituted oxazolidine-type pseudoprolines (CF3-PsiPro) into peptide chains have
      been studied. While standard protocols can be used for the peptide coupling
      reaction at the C-terminal position of the CF3-PsiPro, acid chloride activation
      has to be used for the peptide coupling reaction at the N-terminal position to
      overcome the decrease of nucleophilicity of the CF3-PsiPro. We demonstrate that
      the N-amidification of a diastereomeric mixture of CF3-PsiPro using Fmoc
      protected amino acid chloride without base gave the corresponding dipeptides as a
      single diastereomer (6 examples). The ratio of the cis and trans amide bond
      conformers was determined by NMR study, highlighting the role of the Xaa side
      chains in the control of the peptide backbone conformation. Finally a tripeptide
      bearing a central CF3-PsiPro has been successfully synthesized. 

PMID- 24032631
TI  - Autophagy activation by interferon-gamma via the p38 mitogen-activated protein
      kinase signalling pathway is involved in macrophage bactericidal activity.
AB  - Macrophages are involved in many essential immune functions. Their role in cell
      autonomous innate immunity is reinforced by interferon-gamma (IFN-gamma), which
      is mainly secreted by proliferating type 1 T helper cells and natural killer
      cells. Previously, we showed that IFN-gamma activates autophagy via p38 mitogen
      activated protein kinase (p38 MAPK), but the biological importance of this
      signalling pathway has not been clear. Here, we found that macrophage
      bactericidal activity increased by 4 hr after IFN-gamma stimulation. Inducible
      nitric oxide synthase (NOS2) is a major downstream effector of the Janus kinase
      signal transducer and activator of transcription 1 signalling pathway that
      contributes to macrophage bactericidal activity via nitric oxide (NO) generation.
      However, no NO generation was observed after 4 hr of IFN-gamma stimulation, and
      macrophage bactericidal activity at early stages after IFN-gamma stimulation was
      not affected by the NOS inhibitors, NG-methyl-l-arginine acetate salt and
      diphenyleneiodonium chloride. These results suggest that an NOS2-independent
      signalling pathway is involved in IFN-gamma-mediated bactericidal activity. We
      also found that this macrophage activity was attenuated by the addition of the
      p38 MAPK inhibitors, PD 169316, SB 202190, and SB 203580, or by the expression of
      short hairpin RNA against p38alpha or the essential factors for autophagy, Atg5
      and Atg7. Collectively, our results suggest that the IFN-gamma-mediated autophagy
      via p38 MAPK, without the involvement of NOS2, also contributes to the ability of
      macrophages to kill intracellular bacteria. These observations provide direct
      evidence that p38 MAPK-mediated autophagy can support IFN-gamma-mediated cell
      autonomous innate immunity.

PMID- 24032633
TI  - Mouthparts and their setae of the intertidal isopod Cirolana harfordi.
AB  - The cirolanid isopod Cirolana harfordi is described as a scavenger and a predator
      that lives in the intertidal region. In order to understand the microanatomy of
      the mouthparts and the setae that allow this animal to handle and eat its food, a
      scanning electron microscopy study was conducted. C. harfordi displays a variety
      in the types of setae distributed on its mouthparts in a site-specific fashion,
      including complex setae placed on the medial edge of the maxilliped and maxilla.
      Terminal pores in some setae were found to contain a cupule, which is a
      hemispherical structure, housed in the concave recess of the pore, which
      demonstrates that the pore is more than merely a thinning of the cuticle as has
      been proposed. Future studies on setal morphology are needed for comparative
      microanatomy of cirolanid isopods. 

PMID- 24032632
TI  - Nucleic acid oxidation: an early feature of Alzheimer's disease.
AB  - Studies of oxidative damage during the progression of Alzheimer's disease (AD)
      suggest its central role in disease pathogenesis. To investigate levels of
      nucleic acid oxidation in both early and late stages of AD, levels of multiple
      base adducts were quantified in nuclear and mitochondrial DNA from the superior
      and middle temporal gyri (SMTG), inferior parietal lobule (IPL), and cerebellum
      (CER) of age-matched normal control subjects, subjects with mild cognitive
      impairment, preclinical AD, late-stage AD, and non-AD neurological disorders
      (diseased control; DC) using gas chromatography/mass spectrometry. Median levels
      of multiple DNA adducts in nuclear and mitochondrial DNA were significantly (p <=
      0.05) elevated in the SMTG, IPL, and CER in multiple stages of AD and in DC
      subjects. Elevated levels of fapyguanine and fapyadenine in mitochondrial DNA
      suggest a hypoxic environment early in the progression of AD and in DC subjects.
      Overall, these data suggest that oxidative damage is an early event not only in
      the pathogenesis of AD but is also present in neurodegenerative diseases in
      general. Levels of oxidized nucleic acids in nDNA and mtDNA were found to be
      significantly elevated in mild cognitive impairment (MCI), preclinical
      Alzheimer's disease (PCAD), late-stage AD (LAD), and a pooled diseased control
      group (DC) of frontotemporal dementia (FTD) and dementia with Lewy bodies (DLB)
      subjects compared to normal control (NC) subjects. Nucleic acid oxidation peaked
      early in disease progression and remained elevated. The study suggests nucleic
      acid oxidation is a general event in neurodegeneration.

PMID- 24032634
TI  - Anti-Mullerian hormone levels in salpingectomized compared with
      nonsalpingectomized women with tubal factor infertility and women with
      unexplained infertility.
AB  - OBJECTIVE: To investigate the consequence of salpingectomy on ovarian reserve by
      measuring anti-Mullerian hormone (AMH) levels before in vitro fertilization (IVF)
      treatment in salpingectomized women compared with nonsalpingectomized women with
      tubal factor infertility, women with unexplained infertility and fertile control
      women, and to evaluate whether AMH levels could predict IVF outcome. DESIGN:
      Cross-sectional study extended from a previous prospective study. SETTING: Four
      university fertility clinics. PATIENTS: Seventy-one women with infertility and 21
      fertile controls. INTERVENTIONS: Blood sampling and IVF and embryo transfer in
      the following cycle. MAIN OUTCOME MEASURE: Serum AMH levels and oocytes
      retrieved. RESULTS: Anti-Mullerian hormone levels were significantly lower in the
      salpingectomy infertility group (median 16.1, range 5.2-54 pmol/L) compared with
      the nonsalpingectomy tubal factor infertility group (median 23.4, range 3.5-50
      pmol/L; p = 0.04). In all groups, AMH levels correlated positively with the
      number of oocytes retrieved. AMH predicted poor response (five or fewer oocytes)
      with a sensitivity and specificity of 90% and 70%, at a 19 pmol/L cut-off value.
      CONCLUSION: Serum AMH levels were lower in salpingectomized women compared with
      women with tubal factor infertility and preserved Fallopian tubes, indicating
      that ovarian reserve might be affected by tubal surgery. Furthermore, serum AMH
      levels could predict a poor oocyte response (five or fewer oocytes) in the study
      group of infertile women.

PMID- 24032635
TI  - Identification of human leucocyte antigen (HLA)-A*0201-restricted cytotoxic T
      lymphocyte epitopes derived from HLA-DObeta as a novel target for multiple
      myeloma.
AB  - Despite the recent development of effective therapeutic agents against multiple
      myeloma (MM), new therapeutic approaches, including immunotherapies, remain to be
      developed. Here we identified novel human leucocyte antigen (HLA)-A*0201 (HLA-A2)
      restricted cytotoxic T lymphocyte (CTL) epitopes from a B cell specific molecule
      HLA-DObeta (DOB) as a potential target for MM. By DNA microarray analysis, the
      HLA-DOB expression in MM cells was significantly higher than that in normal
      plasma cells. Twenty-five peptides were predicted to bind to HLA-A2 from the
      amino acid sequence of HLA-DOB. When screened for the immunogenicity in HLA-A2
      transgenic mice immunized with HLA-DOB cDNA, 4 peptides were substantially
      immunogenic. By mass spectrometry analysis of peptides eluted from HLA-A2
      immunoprecipitates of MM cell lines, only two epitopes, HLA-DOB232-240
      (FLLGLIFLL) and HLA-DOB185-193 (VMLEMTPEL), were confirmed for their physical
      presence on cell surface. When healthy donor blood was repeatedly stimulated in
      vitro with these two peptides and assessed by antigen-specific gamma-interferon
      secretion, HLA-DOB232-240 was more immunogenic than HLA-DOB185-193 .
      Additionally, the HLA-DOB232-240 -specific CTLs, but not the HLA-DOB185-193 
      specific CTLs, displayed an major histocompatibility complex class I-restricted
      reactivity against MM cell lines expressing both HLA-A2 and HLA-DOB. Taken
      together, based on the physical presence on tumour cell surface and high
      immunogenicity, HLA-DOB232-240 might be useful for developing a novel
      immunotherapy against MM. 

PMID- 24032636
TI  - Influence of a modified propofol equilibration rate constant (k(e0)) on the
      effect-site concentration at loss and recovery of consciousness with the Marsh
      model.
AB  - This study compared the predicted effect-site concentration of propofol at loss
      and recovery of consciousness when using target-controlled infusion devices with
      the same pharmacokinetic model (Marsh) but a different plasma effect-site
      equilibration rate constant (ke0 ), the Diprifusor(TM) (ke0 0.26 min(-1) ) and
      Base PrimeaTM (ke0 1.21 min(-1) ). We studied 60 female patients undergoing minor
      gynaecological surgery under general anaesthesia. Although the total dose of
      propofol and time until loss of consciousness were comparable, the effect-site
      concentration at loss of consciousness was significantly lower with the
      Diprifusor than with the Base Primea (1.2 (0.3) MUg.ml(-1) vs 4.5 (0.9) MUg.ml(
      1) , respectively, p < 0.001). The effect-site concentration at recovery of
      consciousness was significantly higher with the Diprifusor than with the Base
      Primea (1.8 (0.4) MUg.ml(-1) vs 1.5 (0.2) MUg.ml(-1) , respectively, p = 0.01).
      In conclusion, the effect-site concentration of propofol differs depending on the
      ke0 , despite the use of the same pharmacokinetic model. Therefore, the ke0
      should be considered when predicting loss and recovery of consciousness based on
      the effect-site concentration of propofol.

PMID- 24032638
TI  - Closing the circle: a thirty-year retrospective on the AIDS/blood epidemic.

PMID- 24032639
TI  - Hepatitis B virus reactivation after ustekinumab treatment.

PMID- 24032640
TI  - Cardioprotective 3',4'-dihydroxyflavonol attenuation of JNK and p38(MAPK)
      signalling involves CaMKII inhibition.
AB  - DiOHF (3',4'-dihydroxyflavonol) is cardioprotective against I/R
      (ischaemia/reperfusion) injury. The biological activities of flavonols are
      associated with kinase modulation to alter cell signalling. We thus investigated
      the effects of DiOHF on the activation of MAPKs (mitogen-activated protein
      kinases) that regulate the cardiac stress response. In an ovine model of I/R, JNK
      (c-Jun N-terminal kinase), p38(MAPK), ERK (extracellular-signal-regulated kinase)
      and Akt were activated, and NP202, a pro-drug of DiOHF, reduced infarct size and
      inhibited JNK and p38(MAPK) activation, whereas ERK and Akt phosphorylation were
      unaltered. Similarly, in cultured myoblasts, DiOHF pre-treatment preserved
      viability and inhibited activation of JNK and p38(MAPK), but not ERK in response
      to acute oxidative and chemotoxic stress. Furthermore, DiOHF prevented stress
      activation of the direct upstream regulators MKK4/7 (MAPK kinase 4/7) and MKK3/6
      respectively. We utilized small-molecule affinity purification and identified
      CaMKII (Ca(2+)/calmodulin-dependent protein kinase II) as a kinase targeted by
      DiOHF and demonstrated potent CaMKII inhibition by DiOHF in vitro. Moreover, the
      specific inhibition of CaMKII with KN-93, but not KN-92, prevented oxidative
      stress-induced activation of JNK and p38(MAPK). The present study indicates DiOHF
      inhibition of CaMKII and attenuation of MKK3/6->p38(MAPK) and MKK4/7->JNK
      signalling as a requirement for the protective effects of DiOHF against stress
      stimuli and myocardial I/R injury.

PMID- 24032637
TI  - WNT/Frizzled signalling: receptor-ligand selectivity with focus on FZD-G protein
      signalling and its physiological relevance: IUPHAR Review 3.
AB  - The wingless/int1 (WNT)/Frizzled (FZD) signalling pathway controls numerous
      cellular processes such as proliferation, differentiation, cell-fate decisions,
      migration and plays a crucial role during embryonic development. Nineteen
      mammalian WNTs can bind to 10 FZDs thereby activating different downstream
      pathways such as WNT/beta-catenin, WNT/planar cell polarity and WNT/Ca(2+) .
      However, the mechanisms of signalling specification and the involvement of
      heterotrimeric G proteins are still unclear. Disturbances in the pathways can
      lead to various diseases ranging from cancer, inflammatory diseases to metabolic
      and neurological disorders. Due to the presence of seven-transmembrane segments,
      evidence for coupling between FZDs and G proteins and substantial structural
      differences in class A, B or C GPCRs, FZDs were grouped separately in the IUPHAR
      GPCR database as the class FZD within the superfamily of GPCRs. Recently,
      important progress has been made pointing to a direct activation of G proteins
      after WNT stimulation. WNT/FZD and G protein coupling remain to be fully
      explored, although the basic observation supporting the nature of FZDs as GPCRs
      is compelling. Because the involvement of different (i) WNTs; (ii) FZDs; and
      (iii) intracellular binding partners could selectively affect signalling
      specification, in this review we present the current understanding of
      receptor/ligand selectivity of FZDs and WNTs. We pinpoint what is known about
      signalling specification and the physiological relevance of these interactions
      with special emphasis on FZD-G protein interactions.

PMID- 24032641
TI  - Deep brain stimulation of the centromedian thalamic nucleus for the treatment of
      generalized and frontal epilepsies.
AB  - PURPOSE: Deep brain stimulation (DBS) of the thalamus is an emerging surgical
      option for people with medically refractory epilepsy that is not suitable for
      resective surgery, or in whom surgery has failed. Our main aim was to evaluate
      the efficacy of bilateral centromedian thalamic nucleus (CMN) DBS for seizure
      control in generalized epilepsy and frontal lobe epilepsy with a two-center,
      single-blind, controlled trial. METHODS: Participants were adults with refractory
      generalized or frontal lobe epilepsy. Seizure diaries were kept by
      patients/carers prospectively from enrollment. The baseline preimplantation
      period was followed by a control period consisting of a blind stimulation-OFF
      phase of at least 3 months, a 3-month blind stimulation-ON phase, and a 6-month
      unblinded stimulation-ON phase. The control period was followed by an unblinded
      long-term extension phase with stimulation-ON in those patients in whom
      stimulation was thought to be effective. KEY FINDINGS: Eleven patients were
      recruited at King's College Hospital (London, United Kingdom United Kingdom) and
      at University Hospital La Princesa (Madrid, Spain). Among the five patients with
      frontal lobe epilepsy, only one patient had >50% improvement in seizure frequency
      during the blind period. In the long-term extension phase, two patients with
      frontal lobe epilepsy had >50% improvement in seizure frequency. All six patients
      with generalized epilepsy had >50% improvement in seizure frequency during the
      blind period. In the long-term extension phase, five of the six patients showed
      >50% improvement in the frequency of major seizures (one became seizure free, one
      had >99% improvement, and three had 60-95% reduction in seizure frequency). Among
      patients with generalized epilepsy, the DBS implantation itself appears to be
      effective, as two patients remained seizure free during 12 and 50 months with DBS
      OFF, and the remaining four had 50-91% improvement in the initial 3 months with
      DBS OFF. SIGNIFICANCE: DBS implantation and stimulation of the CMN appears to be
      a safe and efficacious treatment, particularly in patients with refractory
      generalized epilepsy. CMN stimulation was not as effective in frontal lobe
      epilepsy, which requires further studies. DBS of the CMN should be considered as
      a treatment option, particularly in patients with refractory generalized epilepsy
      syndromes.

PMID- 24032642
TI  - Revision of hemoproteid genera and description and redescription of two species
      of chelonian hemoproteid parasites.
AB  - Pigmented hemosporidian parasites that do not exhibit erthyrocytic schizogony,
      and infect birds, chelonians, and squamates, have been classified in various
      genera over time. These classifications have reflected vertebrate hosts, insect
      vectors, and variations in morphology and life history observed in representative
      species. Side-necked turtles ( Podocnemis spp.) from the Peruvian Amazon were
      screened for hemoparasites and 2 species of hemosporid parasites infecting these
      hosts were observed. Molecular phylogenetic analysis of these new isolates, along
      with parasites from lizards, a snake, and a variety of Haemoproteus species from
      birds from both the Haemoproteus and Parahaemoproteus subgenera, strongly support
      the separation of the non-avian parasites into a separate genus. The name with
      precedent for this group is Haemocystidium Castellani and Willey 1909, and we
      propose that subgeneric classification of Haemocystidium and Simondia be applied
      to parasites of squamates and chelonians, respectively. We offer a description of
      Haemocystidium (Simondia) pacayae n. sp. and a redescription of Haemocystidium
      (Simondia) peltocephali ( Lainson and Naiff 1998 , n. comb.) Morphologically, the
      parasites are quite similar, with H. pacayae slightly more elongated than H.
      peltocephali. The discovery and identification of parasite species is urgent,
      especially in endangered species and wildlife inhabiting rapidly declining
      ecosystems such as the Amazon.

PMID- 24032643
TI  - Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a
      review.
AB  - INTRODUCTION: Compelling evidence has highlighted the complex pleiotropic
      functions elicited by the melatonin in cancer cells. Melatonin behaves as a
      'smart killer', i.e., modulating anti-apoptotic processes in normal cells, and
      triggering pro-apoptotic signals in cancer cells. AREAS COVERED: Melatonin
      induces programmed cell death in a wide range of different tumors (breast, gastro
      intestinal, hematological, prostate, osteosarcoma, melanoma, kidney, etc...).
      Mechanisms of action and molecular pathways involved in pro-apoptotic processes
      under melatonin treatment are discussed. EXPERT OPINION: Melatonin involvement in
      apoptotic processes is a new and relevant field of investigation. Even in tumor
      models unresponsive to melatonin alone, this hormone can significantly amplify
      the cytostatic and the cytotoxic effects triggered by other compounds or
      conventional drugs. We are far from having a satisfactory understanding about how
      and when melatonin exerts its beneficial effects. Melatonin in the nanomolar
      range activates the intrinsic and/or the extrinsic apoptotic pathway in cancer
      cells, namely through an increase in the p53/MDM2p ratio and downregulation of
      Sirt1. This finding is of great relevance since there is intense research ongoing
      to identify nontoxic feasible inhibitors of MDM2 and Sirt1. Melatonin should be
      evaluated for the management of those cancers where both of these are
      overexpressed and functionally strategic.

PMID- 24032644
TI  - Correlating the plasmonic and structural evolutions during the sulfidation of
      silver nanocubes.
AB  - Ag/Ag2S hybrid nanostructures have recently received much attention, because of
      their synthetically tunable plasmonic properties and enhanced chemical stability.
      Sulfidation of pregrown Ag nanocrystals is a facile process for making Ag/Ag2S
      nanostructures. Understanding the sulfidation process can help in finely
      controlling the compositional and structural parameters and in turn tailoring the
      plasmonic properties. Herein we report on our study of the structural and
      plasmonic evolutions during the sulfidation process of Ag nanocubes, which is
      carried out at both the ensemble and single-particle levels. Ensemble extinction
      measurements show that sulfidation first causes the disappearance of the high
      order triakontadipolar plasmon modes, which have electric charges located on the
      sharp vertices and edges of Ag nanocubes, suggesting that sulfidation starts at
      the vertices of Ag nanocubes. As sulfidation goes on, the dipolar plasmon peak
      gradually red-shifts, with its intensity first decreasing and then increasing.
      Electron microscopy characterizations reveal that sulfidation progresses from the
      outer region to the center of Ag nanocubes. The cubic shape is maintained
      throughout the sulfidation process, with the edge length being increased
      gradually. Single-particle scattering measurements show that the dipolar plasmon
      peak red-shifts and decreases in intensity during sulfidation. An additional
      scattering peak appears at a shorter wavelength at the late stage of sulfidation.
      The difference in the sulfidation behavior between ensemble and single-particle
      measurements is understood with electrodynamic simulations. During ensemble
      measurements, the Ag core is increasingly truncated, and it becomes a nanosphere
      eventually. Sulfidation stops at an intermediate stage. During single-particle
      measurements, Ag nanocubes are completely transformed into Ag2S, leading to the
      observation of the shorter-wavelength scattering peak. 

PMID- 24032645
TI  - Immunological changes and increased expression of myxovirus resistance protein a
      in thyroid tissue of patients with recent onset and untreated Graves' disease.
AB  - BACKGROUND: Few studies have systematically examined the immune cells that
      infiltrate thyroid tissue at the time of the onset of Graves' disease (GD). The
      role of viruses in the pathogenesis of autoimmune thyroid diseases is
      controversial. The present study analyzed inflammatory responses with respect to
      signs of virus infection. METHODS: Thyroid tissue was obtained from 22 patients
      with newly diagnosed and untreated GD, 24 patients with chronic GD, and 24
      controls. Inflammation was assessed by immunostaining for CD4+ and CD8+ T cells,
      plasma cells (CD138+), and plasmacytoid dendritic cells (PDCs). The production of
      interferon-inducible myxovirus resistance protein A (MxA) was analyzed as a sign
      of virus infection. RESULTS: The degree of thyroid inflammation and fibrosis was
      significantly higher in both patient groups compared with that in controls. The
      number of CD4+ T cells and plasma cells (activated B cells) was significantly
      higher in both patient groups. CD8+ cells were only present in patients with
      chronic disease. MxA expression and the number of PDCs increased only in patients
      with newly diagnosed GD. There was a strong positive correlation between the
      number of PDCs and the number of MxA+ leucocytes. CONCLUSION: The increase in
      CD8+ T cells during the chronic stage of GD suggests that they may play a role in
      progression of the autoimmune process from early to chronic thyroiditis.
      Upregulation of MxA expression during the early stages of the disease, and the
      positive correlation between the number of PDCs and the number of MxA+
      leucocytes, suggests that activated PDCs secrete type I IFNs at the lesion site,
      possibly in response to viral infection.

PMID- 24032646
TI  - Recycling rare earth elements from industrial wastewater with flowerlike nano
      Mg(OH)(2).
AB  - Treatment of wastewater containing low-concentration yet highly-expensive rare
      earth elements (REEs) is one of the vital issues in the REEs separation and
      refining industry. In this work, the interaction and related mechanism between
      self-supported flowerlike nano-Mg(OH)2 and low-concentration REEs wastewater were
      investigated. More than 99% REEs were successfully taken up by nano-Mg(OH)2.
      Further analysis revealed that the REEs could be collected on the surface of
      Mg(OH)2 as metal hydroxide nanoparticles (<5 nm). An ion-exchange model was
      proposed as a critical factor for both guaranteeing the reaction speed and
      maintaining the self-supported structure of the materials. In addition, a method
      was developed to further separate the immobilized REEs and the residual magnesium
      hydroxide by varying the solution pH. In a pilot-scale experiment, the REEs from
      practical wastewater were immobilized effectively at a high flow rate. We
      anticipate this work can provide a good example for the recycling of valuable
      REEs in practical industrial applications. 

PMID- 24032647
TI  - Age, allocation and availability of nonstructural carbon in mature red maple
      trees.
AB  - The allocation of nonstructural carbon (NSC) to growth, metabolism and storage
      remains poorly understood, but is critical for the prediction of stress tolerance
      and mortality. We used the radiocarbon ((14) C) 'bomb spike' as a tracer of
      substrate and age of carbon in stemwood NSC, CO2 emitted by stems, tree ring
      cellulose and stump sprouts regenerated following harvesting in mature red maple
      trees. We addressed the following questions: which factors influence the age of
      stemwood NSC?; to what extent is stored vs new NSC used for metabolism and
      growth?; and, is older, stored NSC available for use? The mean age of extracted
      stemwood NSC was 10 yr. More vigorous trees had both larger and younger stemwood
      NSC pools. NSC used to support metabolism (stem CO2 ) was 1-2 yr old in spring
      before leaves emerged, but reflected current-year photosynthetic products in late
      summer. The tree ring cellulose (14) C age was 0.9 yr older than direct ring
      counts. Stump sprouts were formed from NSC up to 17 yr old. Thus, younger NSC is
      preferentially used for growth and day-to-day metabolic demands. More recently
      stored NSC contributes to annual ring growth and metabolism in the dormant
      season, yet decade-old and older NSC is accessible for regrowth.

PMID- 24032648
TI  - N-heterocyclic carbene catalyzed asymmetric intermolecular Stetter reaction:
      origin of enantioselectivity and role of counterions.
AB  - The mechanism and the role of KOtBu in an enantioselective NHC-catalyzed Stetter
      reaction between p-chlorobenzaldehyde and N-acylamido acrylate is established
      using DFT(M06-2X) methods. The Gibbs free energies are found to be significantly
      lower for transition states with explicit bound KOtBu as compared to the
      conventional pathways without the counterions. An intermolecular proton transfer
      from HOtBu to the prochiral carbon is identified as the stereocontrolling step.
      The computed enantioselectivities are in excellent agreement with the
      experimental results. 

PMID- 24032650
TI  - Efficient convergent synthesis of bi-, tri-, and tetra-antennary complex type N
      glycans and their HIV-1 antigenicity.
AB  - The structural diversity of glycoproteins often comes from post-translational
      glycosylation with heterogeneous N-glycans. Understanding the complexity of
      glycans related to various biochemical processes demands a well-defined synthetic
      sugar library. We report herein a unified convergent strategy for the rapid
      production of bi-, tri-, and tetra-antennary complex type N-glycans with and
      without terminal N-acetylneuraminic acid residues connected via the alpha-2,6 or
      alpha-2,3 linkages. Moreover, using sialyltransferases to install sialic acid can
      minimize synthetic steps through the use of shared intermediates to simplify the
      complicated procedures associated with conventional sialic acid chemistry.
      Furthermore, these synthetic complex oligosaccharides were compiled to create a
      glycan array for the profiling of HIV-1 broadly neutralizing antibodies PG9 and
      PG16 that were isolated from HIV infected donors. From the study of antibody
      PG16, we identified potential natural and unnatural glycan ligands, which may
      facilitate the design of carbohydrate-based immunogens and hasten the HIV vaccine
      development. 

PMID- 24032649
TI  - Antigen-specific B lymphocytes acquire proteoglycan aggrecan from cartilage
      extracellular matrix resulting in antigen presentation and CD4+ T-cell
      activation.
AB  - The majority of studies examining antigen-presenting cell (APC) function have
      focused on the capture and presentation of antigens released from pathogens or
      damaged cells. However, antigen-specific B cells are also capable of efficiently
      extracting antigens that are either tethered to, or integrally part of the plasma
      membrane of various target cells. In this study we show that B cells are also
      highly efficient at extracting integral components of the extracellular matrix
      (ECM) for subsequent presentation. In particular we demonstrate that B cells
      specific for aggrecan, an integral component of cartilage ECM, acquire this
      rheumatoid arthritis candidate autoantigen in both a B-cell-receptor-dependent
      and a contact-dependent manner. We also demonstrate that the subsequent
      presentation of aggregan from ECM leads to CD4(+) T-cell activation and effector
      cell formation. Recent studies have identified B-cell-mediated antigen
      presentation as essential for the development of autoimmunity, but a unique role
      for B cells compared with other APC has yet to be defined. Our findings lead us
      to propose that the acquisition of ECM-derived autoantigens represents a
      mechanism that defines the APC requirement for B cells in the development of
      autoimmunity. 

PMID- 24032651
TI  - Modeling hard clinical end-point data in economic analyses.
AB  - OBJECTIVE: The availability of hard clinical end-point data, such as that on
      cardiovascular (CV) events among patients with type 2 diabetes mellitus, is
      increasing, and as a result there is growing interest in using hard end-point
      data of this type in economic analyses. This study investigated published
      approaches for modeling hard end-points from clinical trials and evaluated their
      applicability in health economic models with different disease features. METHODS:
      A review of cost-effectiveness models of interventions in clinically significant
      therapeutic areas (CV diseases, cancer, and chronic lower respiratory diseases)
      was conducted in PubMed and Embase using a defined search strategy. Only studies
      integrating hard end-point data from randomized clinical trials were considered.
      For each study included, clinical input characteristics and modeling approach
      were summarized and evaluated. RESULTS: A total of 33 articles (23 CV, eight
      cancer, two respiratory) were accepted for detailed analysis. Decision trees,
      Markov models, discrete event simulations, and hybrids were used. Event rates
      were incorporated either as constant rates, time-dependent risks, or risk
      equations based on patient characteristics. Risks dependent on time and/or
      patient characteristics were used where major event rates were >1%/year in models
      with fewer health states (<7). Models of infrequent events or with numerous
      health states generally preferred constant event rates. LIMITATIONS: The detailed
      modeling information and terminology varied, sometimes requiring interpretation.
      CONCLUSIONS: Key considerations for cost-effectiveness models incorporating hard
      end-point data include the frequency and characteristics of the relevant clinical
      events and how the trial data is reported. When event risk is low, simplification
      of both the model structure and event rate modeling is recommended. When event
      risk is common, such as in high risk populations, more detailed modeling
      approaches, including individual simulations or explicitly time-dependent event
      rates, are more appropriate to accurately reflect the trial data.

PMID- 24032652
TI  - Executive function, self-regulation and attribution in acquired brain injury: A
      scoping review.
AB  - Impairments in executive function, self-regulation and attribution individually
      have been implicated in impairment in goal-directed behaviour, resulting in
      reduced participation in daily activities by individuals with brain injury. There
      is minimal literature that explicitly addresses the relationships among these
      constructs, how these may be affected by brain injury and the implications for
      rehabilitation. The objectives of this study were to determine what is known
      about the relationship between executive function, self-regulation and
      attribution, and to understand how these inter-relationships affect goal-directed
      behaviour in adults with acquired brain injury. A scoping review of the cognitive
      neuroscience, neuropsychology, rehabilitation, educational and social psychology
      literature from 1985 to 2011 was performed. The identified literature provided
      definitions of the constructs and insight into the relationships between them
      according to their neural underpinnings and theoretical models. These data also
      provided for the development of a new model illustrating the hypothesised
      relationships between constructs. This review and the model developed, suggest
      that attribution may play an important role in executive function and self
      regulation. Rehabilitation interventions that address formulation of appropriate
      attributions should be considered in conjunction with those targeting self
      regulation and executive function for individuals with brain injury. 

PMID- 24032654
TI  - HE4 and CA125 levels in the preoperative assessment of endometrial cancer
      patients: a prospective multicenter study (ENDOMET).
AB  - OBJECTIVE: To evaluate whether human epididymis protein 4 (HE4) and CA125
      correlate with known high-risk prognostic factors for endometrial cancer. DESIGN:
      Prospective multicenter study. SETTING: Three Danish tertiary gynecological
      oncology centers. POPULATION: A total of 352 patients with endometrial cancer and
      atypical endometrial hyperplasia consecutively referred between 1 September 2009
      and 1 January 2012. METHODS: Preoperative blood samples were obtained from all
      patients. Biomarker levels were correlated with pathological characteristics of
      hysterectomy specimens. MAIN OUTCOME MEASURES: FIGO stage, depth of myometrial
      invasion, cervical involvement, lymph node metastases, and histological type and
      grade of tumor. RESULTS: We found that both HE4 and CA125 were significantly
      positively correlated with histological grade (HE4: p = 0.002 and CA125: p =
      0.027), lymph node metastases (HE4: p = 0.013 and CA125: p < 0.0001), myometrial
      invasion (p < 0.0001) and cervical involvement (p < 0.0001). Furthermore, a
      significant increase was found with increasing FIGO stage for both markers (p <
      0.0001). In a combined index including age, the diagnostic value increases. Area
      under the receiver operating characteristics curves were higher for the index
      compared with the markers individually for all our endpoints. The calculated
      plots for the combined index may assist gynecologists in predicting the risk of
      deep myometrial invasion, cervical involvement and lymph node metastases. The
      analyses emphasize that the combined markers should be used in the prediction of
      prognostic factors. CONCLUSION: This study confirmed that the markers are
      significantly elevated in patients with prognostic high-risk factors and may,
      therefore, be used as an additional tool in combination with imaging and clinical
      information when planning the treatment of endometrial cancer patients.

PMID- 24032653
TI  - The GPCR, class C, group 6, subtype A (GPRC6A) receptor: from cloning to
      physiological function.
AB  - GPRC6A (GPCR, class C, group 6, subtype A) is a class C GPCR that has been cloned
      from human, mouse and rat. Several groups have shown that the receptor is
      activated by a range of basic and small aliphatic L-alpha-amino acids of which L
      arginine, L-lysine and L-ornithine are the most potent compounds with EC50 values
      in the mid-micromolar range. In addition, several groups have shown that the
      receptor is either directly activated or positively modulated by divalent cations
      such as Ca(2+) albeit in concentrations above 5 mM, which is above the
      physiological concentration in most tissues. More recently, the peptide
      osteocalcin and the steroid testosterone have also been suggested to be
      endogenous GPRC6A agonists. The receptor is widely expressed in all three species
      which, along with the omnipresence of the amino acids and divalent cation
      ligands, suggest that the receptor could be involved in a broad range of
      physiological functions. So far, this has mainly been addressed by analyses of
      genetically modified mice where the GPRC6A receptor has been ablated. Although
      there has been some discrepancies among results reported from different groups,
      there is increasing evidence that the receptor is involved in regulation of
      inflammation, metabolism and endocrine functions. GPRC6A could thus be an
      interesting target for new drugs in these therapeutic areas.

PMID- 24032655
TI  - Distinctive immunoglobulin VH gene features of cutaneous marginal zone lymphomas
      in Asian cases.

PMID- 24032657
TI  - Design and characterization of Amoitone B-loaded nanostructured lipid carriers
      for controlled drug release.
AB  - Amoitone B, a novel compound chemically synthesized as the analogue of
      cytosporone B, has been proved to own superior affinity with Nur77 than its
      parent compound and exhibit notable anticancer activity. However, its application
      is seriously restricted due to the water-insolubility and short biological half
      time. The aim of this study was to construct an effective delivery system for
      Amoitone B to realize sustained release, thus prolong drug circulation time in
      body and improve the bioavailability. Nanostructured lipid carriers (NLC) act as
      a new type of colloidal drug delivery system, which offer the advantages of
      improved drug loading and sustained release. Amoitone B-loaded NLC (AmB-NLC)
      containing glyceryl monostearate (GMS) and various amounts of medium chain
      triglycerides (MCT) were successfully prepared by emulsion-evaporation and low
      temperature-solidification technology with a particle size of about 200 nm and a
      zeta potential value of about -20 mV. The results of X-ray diffraction and DSC
      analysis showed amorphous crystalline state of Amoitone B in NLC. Furthermore,
      the drug entrapment efficacy (EE) was improved compared with solid lipid
      nanoparticles (SLN). The EE range was from 71.1% to 84.7%, enhanced with the
      increase of liquid lipid. In vitro drug release studies revealed biphasic drug
      release patterns with burst release initially and prolonged release afterwards
      and the release was accelerated with augment of liquid lipid. These results
      demonstrated that AmB-NLC could be a promising delivery system to control drug
      release and improve loading capacity, thus prolong drug action time in body and
      enhance the bioavailability.

PMID- 24032656
TI  - Genetic sensor for strong methylating compounds.
AB  - Methylating chemicals are common in industry and agriculture and are often toxic,
      partly due to their propensity to methylate DNA. The Escherichia coli Ada protein
      detects methylating compounds by sensing aberrant methyl adducts on the
      phosphoester backbone of DNA. We characterize this system as a genetic sensor and
      engineer it to lower the detection threshold. By overexpressing Ada from a
      plasmid, we improve the sensor's dynamic range to 350-fold induction and lower
      its detection threshold to 40 MUM for methyl iodide. In eukaryotes, there is no
      known sensor of methyl adducts on the phosphoester backbone of DNA. By fusing the
      N-terminal domain of Ada to the Gal4 transcriptional activation domain, we built
      a functional sensor for methyl phosphotriester adducts in Saccharomyces
      cerevisiae. This sensor can be tuned to variable specifications by altering the
      expression level of the chimeric sensor and changing the number of Ada operators
      upstream of the Gal4-sensitive reporter promoter. These changes result in a
      detection threshold of 28 MUM and 5.2-fold induction in response to methyl
      iodide. When the yeast sensor is exposed to different SN1 and SN2 alkylating
      compounds, its response profile is similar to that observed for the native Ada
      protein in E. coli, indicating that its native function is retained in yeast.
      Finally, we demonstrate that the specifications achieved for the yeast sensor are
      suitable for detecting methylating compounds at relevant concentrations in
      environmental samples. This work demonstrates the movement of a sensor from a
      prokaryotic to eukaryotic system and its rational tuning to achieve desired
      specifications.

PMID- 24032658
TI  - Synthesis of eight stereoisomers of pochonicine: nanomolar inhibition of beta-N
      acetylhexosaminidases.
AB  - Pochonicine, the first naturally occurring polyhydroxylated pyrrolizidine
      containing an acetamidomethyl group, which was isolated from Pochonia
      suchlasporia var. suchlasporia TAMA 87, together with its enantiomer and their C
      1 and/or C-3 epimers, have been synthesized from the sugar-derived cyclic
      nitrones 9D and 9L, respectively. An in-depth NMR study showed that both the (1)H
      and (13)C NMR spectra of the synthetic pochonicines (1D and 1L) matched very well
      with those of natural pochonicine in D2O, which unequivocally determined the
      relative configuration of the natural product as 1D or 1L. In addition,
      comparison of the optical rotations of the synthetic pochonicines and that of the
      natural product, but more convincingly their glycosidase inhibition profiles,
      confirmed the absolute configuration of natural pochonicine as
      1R,3S,5R,6R,7S,7aR. Thereby, the structure of natural pochonicine was
      unequivocally determined as (+)-(1R,3S,5R,6R,7S,7aR)-pochonicine (1D).
      Glycosidase inhibition experiments showed that natural pochonicine 1D and its
      epimers 2D, 3D, and 4D all are powerful inhibitors of hexosaminidases (five beta
      N-acetylglucosaminidases and two beta-N-acetylgalactosaminidases) while their
      enantiomers 1L, 2L, 3L, and 4L are much weaker inhibitors of the same enzymes. (
      )-3-epi-Pochonicine (2L) was found to be a potent and selective inhibitor of
      alpha-l-rhamnosidase. None of the compounds showed any inhibition of alpha
      GalNAcase. 

PMID- 24032659
TI  - Kinetic study of seawater reverse osmosis membrane fouling.
AB  - Reverse osmosis (RO) membrane fouling is not a static state but a dynamic
      phenomenon. The investigation of fouling kinetics and dynamics of change in the
      composition of the foulant mass is essential to elucidate the mechanism of
      fouling and foulant-foulant interactions. The aim of this work was to study at a
      lab scale the fouling process with an emphasis on the changes in the relative
      composition of foulant material as a function of operating time. Fouled membrane
      samples were collected at 8 h, and 1, 2, and 4 weeks on a lab-scale RO unit
      operated in recirculation mode. Foulant characterization was performed by CLSM,
      AFM, ATR-FTIR, pyrolysis GC-MS, and ICP-MS techniques. Moreover, measurement of
      active biomass and analysis of microbial diversity were performed by ATP analysis
      and DNA extraction, followed by pyro-sequencing, respectively. A progressive
      increase in the abundance of almost all the foulant species was observed, but
      their relative proportion changed over the age of the fouling layer. Microbial
      population in all the membrane samples was dominated by specific groups/species
      belonging to Proteobacteria and Actinobacteria phyla; however, similar to abiotic
      foulant, their relative abundance also changed with the biofilm age. 

PMID- 24032660
TI  - Heterogeneity of alleles encoding high- and low-prevalence red blood cell
      antigens across Africa: useful data to facilitate transfusion in African
      patients.
AB  - Ethnic variations in red blood cell (RBC) antigens can be a source of
      alloimmunization, especially in migrant populations. To improve transfusion
      safety in continental Africa and countries with African migrants, we performed
      RBC genotyping to determine allele frequencies coding for high- and low
      prevalence antigens. A total of 481 blood samples were collected in ethnic groups
      from West, Central and East Africa. Molecular typing was performed using a
      polymerase chain reaction - reverse sequence specific oligonucleotide method.
      Results demonstrated no DI*1, DI*3, YT*2, SC*2, LW*7, KN*2 alleles in any sample
      and the CO*2 allele was rare. The frequency of LU*1 was comparable to that of
      European-Caucasians (2%) except in Biaka pygmies (8%). The frequency of CROM*-1
      was high in Mbuti pygmies (13%). High frequency of KN*7 and KN*6 may reflect
      selection pressure in the countries investigated. Analysis of Dombrock allele
      patterns confirmed uneven distribution of the DO*1 and DO*2 alleles with high
      frequencies of DO*-4 and DO*-5 in all groups. Altogether, findings demonstrated
      extensive allele-frequency heterogeneity across Africa and suggested that
      knowledge of patient ethnicity gives information about the high-prevalence
      antigens that may be lacking. These data are medically useful to support
      transfusion care of African migrants living in countries where the majority of
      the population is from a different ethnical background.

PMID- 24032661
TI  - Adaptive characterization of recrystallization kinetics in IF steel by electron
      backscatter diffraction.
AB  - In this study, a rigorous methodology for quantifying recrystallization kinetics
      by electron backscatter diffraction is proposed in order to reduce errors
      associated with the operator's skill. An adaptive criterion to determine
      adjustable grain orientation spread depending on the recrystallization stage is
      proposed to better identify the recrystallized grains in the partially
      recrystallized microstructure. The proposed method was applied in characterizing
      the microstructure evolution during annealing of interstitial-free steel cold
      rolled to low and high true strain levels of 0.7 and 1.6, respectively. The
      recrystallization kinetics determined by the proposed method was found to be
      consistent with the standard method of Vickers microhardness. The application of
      the proposed method to the overall recrystallization stages showed that it can be
      used for the rigorous characterization of progressive microstructure evolution,
      especially for the severely deformed material. 

PMID- 24032662
TI  - Cool microcontact printing to fabricate thermosensitive microgel patterns.
AB  - A facile method, cool microcontact printing (cool MUCP), of fabricating microgel
      patterns under ambient conditions is developed. By using spontaneously condensed
      water on the surface of cold items and the phase transition of polymer microgels
      below the lower critical solution temperature (LCST), a cool
      poly(dimethylsiloxane) (PDMS) stamp can be easily decorated with a thin layer of
      water ink and its pattern can substantially transfer to a substrate that is
      assembled with microgels. As a proof of concept, one kind of thermosensitive
      microgel (i.e., poly(N-isopropylacrylamide) (pNIPAM)) is selected to demonstrate
      our method. A series of pNIPAM microgel patterns with various geometries can be
      easily generated by featured PDMS stamps through a cool MUCP method. The results
      of control experiment using room-temperature PDMS stamps or patterning the pNIPAM
      microgel-incorporated fluorescent probe reveal that condensed cold water on a
      cool PDMS stamp plays an important role when microgel particles are lifted off.
      In addition, it is also observed that both humidity and contact pressure have
      effects on the shapes of the pattern fabricated by cool MUCP, and more precise or
      sophisticate patterns can be obtained by adjusting the conditions. It is
      envisioned that this practically available method, as a good extension to MUCP,
      can facilitate the design of complex patterns, affording great convenience for
      many inherent applications ranging from photonics to chemical sensing to
      biotechnology. 

PMID- 24032663
TI  - Decontamination of prions in a plasma product manufacturing environment.
AB  - BACKGROUND: The high resistance of prions to inactivating treatments requires the
      proper management of decontaminating procedures of equipment in contact with
      materials of human or animal origin destined for medical purposes. Sodium
      hydroxide (NaOH) is widely used today for this purpose as it inactivates a wide
      variety of pathogens including prions. STUDY DESIGN AND METHODS: Several NaOH
      treatments were tested on prions bound to either stainless steel or
      chromatographic resins in industrial conditions with multiple prion strains.
      RESULTS: Data show a strong correlation between inactivation results obtained by
      immunochemical detection of the prion protein and those obtained with infectivity
      assays and establish effective inactivation treatments for prions bound to
      stainless steel or chromatographic resins (ion exchange and affinity), including
      treatments with lower NaOH concentrations. Furthermore, no obvious strain
      specific behavior difference was observed between experimental models.
      CONCLUSION: The results generated by these investigations show that industrial
      NaOH decontamination regimens (in combination with the NaCl elution in the case
      of the chromatography process) attain substantial prion inactivation and/or
      removal between batches, thus providing added assurance to the biologic safety of
      the final plasma-derived medicinal products.

PMID- 24032664
TI  - Serratus plane block: do we need to learn another technique for thoracic wall
      blockade?

PMID- 24032665
TI  - Biological and environmental transformations of copper-based nanomaterials.
AB  - Copper-based nanoparticles are an important class of materials with applications
      as catalysts, conductive inks, and antimicrobial agents. Environmental and safety
      issues are particularly important for copper-based nanomaterials because of their
      potential large-scale use and their high redox activity and toxicity reported
      from in vitro studies. Elemental nanocopper oxidizes readily upon atmospheric
      exposure during storage and use, so copper oxides are highly relevant phases to
      consider in studies of environmental and health impacts. Here we show that copper
      oxide nanoparticles undergo profound chemical transformations under conditions
      relevant to living systems and the natural environment. Copper oxide nanoparticle
      (CuO-NP) dissolution occurs at lysosomal pH (4-5), but not at neutral pH in pure
      water. Despite the near-neutral pH of cell culture medium, CuO-NPs undergo
      significant dissolution in media over time scales relevant to toxicity testing
      because of ligand-assisted ion release, in which amino acid complexation is an
      important contributor. Electron paramagnetic resonance (EPR) spectroscopy shows
      that dissolved copper in association with CuO-NPs are the primary redox-active
      species. CuO-NPs also undergo sulfidation by a dissolution-reprecipitation
      mechanism, and the new sulfide surfaces act as catalysts for sulfide oxidation.
      Copper sulfide NPs are found to be much less cytotoxic than CuO-NPs, which is
      consistent with the very low solubility of CuS. Despite this low solubility of
      CuS, EPR studies show that sulfidated CuO continues to generate some ROS activity
      due to the release of free copper by H2O2 oxidation during the Fenton-chemistry
      based EPR assay. While sulfidation can serve as a natural detoxification process
      for nanosilver and other chalcophile metals, our results suggest that sulfidation
      may not fully and permanently detoxify copper in biological or environmental
      compartments that contain reactive oxygen species.

PMID- 24032667
TI  - Phosphine-catalyzed domino benzannulation: an efficient method to construct
      biaryl skeletons.
AB  - The first phosphine-catalyzed domino benzannulation reaction to prepare a variety
      of functionalized biaryls from allenoates and dienic sulfones is developed. 

PMID- 24032666
TI  - Molecular features of neural stem cells enable their enrichment using
      pharmacological inhibitors of survival-promoting kinases.
AB  - Isolating a pure population of neural stem cells (NSCs) has been difficult since
      no exclusive surface markers have been identified for panning or FACS
      purification. Moreover, additional refinements for maintaining NSCs in culture
      are required, since NSCs generate a variety of neural precursors (NPs) as they
      proliferate. Here, we demonstrate that post-natal rat NPs express low levels of
      pro-apoptotic molecules and resist phosphatidylinositol 3'OH kinase and
      extracellular regulated kinase 1/2 inhibition as compared to late oligodendrocyte
      progenitors. Furthermore, maintaining subventricular zone precursors in LY294002
      and PD98059, inhibitors of PI3K and ERK1/2 signaling, eliminated lineage
      restricted precursors as revealed by enrichment for Nestin(+)/SOX-2(+) cells. The
      cells that survived formed neurospheres and 89% of these neurospheres were
      tripotential, generating neurons, astrocytes, and oligodendrocytes. Without this
      enrichment step, less than 50% of the NPs were Nestin(+)/SOX-2(+) and 42% of the
      neurospheres were tripotential. In addition, neurospheres enriched using this
      procedure produced 3-times more secondary neurospheres, supporting the conclusion
      that this procedure enriches for NSCs. A number of genes that enhance survival
      were more highly expressed in neurospheres compared to late oligodendrocyte
      progenitors. Altogether, these studies demonstrate that primitive neural
      precursors can be enriched using a relatively simple and inexpensive means that
      will facilitate cell replacement strategies using stem cells as well as other
      studies whose goal is to reveal the fundamental properties of primitive neural
      precursors.

PMID- 24032669
TI  - A survey of mycotoxins in domestic rice in Iran by liquid chromatography tandem
      mass spectrometry.
AB  - In this study, a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method
      was applied for the simultaneous detection and quantification of a broad spectrum
      of mycotoxins and fungal metabolites in domestic rice in Iran. A total of 20
      fungal metabolites were detected in 65 rice samples. The result showed that all
      of the samples were contaminated to at least one mycotoxin. The most prevalent
      fungal metabolites were brevianamide F (81.5%), emodin (46.1%) and tryptophol
      (43.1%). The occurrence of aflatoxin B1 (AFB1), ochratoxin A (OTA), zearalenone
      (ZEN) and fumonisin B1 (FB1) was 21.5%, 4.6%, 29.2% and 9.2%, respectively. No
      detectable level of deoxynivelenol was found in any of the samples. The mean
      level of regulated mycotoxins was lower than the maximum limit. Co-occurrence of
      AF1-ZEN, ZEN-OTA and FB1-ZEN were observed in 4.6%, 3.1% and 4.6% of samples,
      respectively. This is the first report indicating the contamination of domestic
      rice in Iran with mycotoxins such as alternaria metabolites, citrinin, tryptophol
      and kojic acid.

PMID- 24032671
TI  - Evidence to practice commentary: advancing the evidence and the right to
      participation.

PMID- 24032670
TI  - Microstructural integrity of early- versus late-myelinating white matter tracts
      in medial temporal lobe epilepsy.
AB  - PURPOSE: Patients with medial temporal lobe epilepsy (MTLE) exhibit structural
      brain damage involving gray matter (GM) and white matter (WM). The mechanisms
      underlying tissue loss in MTLE are unclear and may be associated with a
      combination of seizure excitotoxicity and WM vulnerability. The goal of this
      study was to investigate whether late-myelinating WM tracts are more vulnerable
      to injury in MTLE compared with early myelinating tracts. METHODS: Diffusional
      kurtosis imaging scans were obtained from 25 patients with MTLE and from 36
      matched healthy controls. Diffusion measures from regions of interest (ROIs) for
      both late- and early myelinating WM tracts were analyzed. Regional Z-scores were
      computed with respect to normal controls to compare WM in early myelinating
      tracts versus late-myelinating tracts. KEY FINDINGS: We observed that late
      myelinating tracts exhibited a larger decrease in mean, axial, and radial
      kurtosis compared with early myelinating tracts. We also observed that the change
      in radial kurtosis was more pronounced in late-myelinating tracts ipsilateral to
      the side of seizure onset. SIGNIFICANCE: These results suggest a developmentally
      based preferential susceptibility of late-myelinating WM tracts to damage in
      MTLE. Brain injury in epilepsy may be due to the pathologic effects of seizures
      in combination with regional WM vulnerability.

PMID- 24032672
TI  - Intermittent BRAF-inhibitor therapy is a feasible option: report of a patient
      with metastatic melanoma.

PMID- 24032673
TI  - Dynamic conformational switching in the chemokine ligand is essential for G
      protein-coupled receptor activation.
AB  - Chemokines mediate diverse functions from organogenesis to mobilizing leucocytes,
      and are unusual agonists for class-A GPCRs (G-protein-coupled receptors) because
      of their large size and multi-domain structure. The current model for receptor
      activation, which involves interactions between chemokine N-loop and receptor N
      terminal residues (Site-I) and between chemokine N-terminal and receptor
      extracellular loop/transmembrane residues (Site-II), fails to describe
      differences in ligand/receptor selectivity and the activation of multiple
      signalling pathways. In the present study, we show in neutrophil-activating
      chemokine CXCL8 that the highly conserved GP (glycine-proline) motif located
      distal to both N-terminal and N-loop residues couples Site-I and Site-II
      interactions. GP mutants showed large differences from native-like to complete
      loss of function that could not be correlated with the specific mutation,
      receptor affinity or subtype, or a specific signalling pathway. NMR studies
      indicated that the GP motif does not influence Site-I interactions, but molecular
      dynamics simulations suggested that this motif dictates substates of the CXCL8
      conformational ensemble. We conclude that the GP motif enables diverse receptor
      functions by controlling cross-talk between Site-I and Site-II, and further
      propose that the repertoire of chemokine functions is best described by a
      conformational ensemble model in which a network of long-range coupled indirect
      interactions mediate receptor activity.

PMID- 24032674
TI  - HDAC inhibitors restore C-fibre sensitivity in experimental neuropathic pain
      model.
AB  - BACKGROUND AND PURPOSE: Hypoesthesia is a clinical feature of neuropathic pain.
      The feature is partly explained by the evidence of epigenetic repression of Nav
      1.8 sodium channel in the dorsal root ganglion (DRG). EXPERIMENTAL APPROACH: We
      investigated the possibility of trichostatin A (TSA), valproic acid (VPA) and
      suberoylanilide hydroxamic acid (SAHA) to reverse the unique C-fibre sensitivity
      observed following partial ligation of sciatic nerve in mice. KEY RESULTS: Nerve
      injury-induced down-regulation of DRG Nav 1.8 sodium channel and C-fibre-related
      hypoesthesia were reversed by TSA, VPA and SAHA treatments, which inhibit histone
      deacetylase (HDAC), and increase histone acetylation at the regulatory sequence
      of Nav 1.8. CONCLUSIONS AND IMPLICATIONS: Taken together, these studies provide
      the evidence that hypoesthesia and underlying down-regulation of Nav 1.8,
      negative symptoms observed in nerve injury-induced neuropathic pain models are
      regulated by an epigenetic chromatin remodelling through HDAC-related
      machineries.

PMID- 24032676
TI  - Therapeutic potential of amniotic fluid-derived cells for treating the injured
      nervous system.
AB  - There is a need for improved therapy for acquired brain injury, which has proven
      resistant to treatment by numerous drugs in clinical trials and continues to
      represent one of the leading causes of disability worldwide. Research into cell
      based therapies for the treatment of brain injury is growing rapidly, but the
      ideal cell source has yet to be determined. Subpopulations of cells found in
      amniotic fluid, which is readily obtained during routine amniocentesis, can be
      easily expanded in culture, have multipotent differentiation capacity, are non
      tumourigenic, and avoid the ethical complications associated with embryonic stem
      cells, making them a promising cell source for therapeutic purposes. Beneficial
      effects of amniotic fluid cell transplantation have been reported in various
      models of nervous system injury. However, evidence that amniotic fluid cells can
      differentiate into mature, functional neurons in vivo and incorporate into the
      existing circuitry to replace lost or damaged neurons is lacking. The mechanisms
      by which amniotic fluid cells improve outcomes after experimental nervous system
      injury remain unclear. However, studies reporting the expression and release of
      neurotrophic, angiogenic, and immunomodulatory factors by amniotic fluid cells
      suggest they may provide neuroprotection and (or) stimulate endogenous repair and
      remodelling processes in the injured nervous system. In this paper, we address
      recent research related to the neuronal differentiation of amniotic fluid-derived
      cells, the therapeutic efficacy of these cells in animal models of nervous system
      injury, and the possible mechanisms mediating the positive outcomes achieved by
      amniotic fluid cell transplantation.

PMID- 24032677
TI  - Calmodulin activation of polo-like kinase 1 is required during mitotic entry.
AB  - Polo-like kinase 1 (Plk1) is a conserved key regulator of the G2/M transition,
      but its upstream spatiotemporal regulators remain unknown. With the help of
      immunofluorescence, co-immunoprecipitation, and glutathione S-transferase (GST)
      pull-down assay, we found that calmodulin (CaM) is one such regulatory molecule
      that associates with Plk1 from G2 to metaphase. More importantly, this
      interaction results in considerable stimulation of Plk1 kinase activity leading
      to hyperphosphorylation of Cdc25C. Our results provide new insight into the role
      of CaM as an upstream regulator of Plk1 activation during mitotic entry. 

PMID- 24032678
TI  - An unusual effect of NADP+ on the thermostability of the nonphosphorylating
      glyceraldehyde-3-phosphate dehydrogenase from Streptococcus mutans.
AB  - Adiabatic differential scanning calorimetry was used to investigate the effect of
      NADP+ on the irreversible thermal denaturation of the nonphosphorylating
      glyceraldehyde-3-phosphate dehydrogenase (GAPN) from Streptococcus mutans. The
      GAPN-NADP+ binary complex showed a strongly decreased thermal stability, with a
      difference of about 20  degrees C between the temperatures of the thermal
      transition peak maxima of the complex and the free protein. This finding was
      similar to the previously described thermal destabilization of GAPN upon binding
      of inorganic phosphate to the substrate binding site and can be interpreted as
      the shift of the equilibrium between 2 conformers of tetrameric GAPN upon
      addition of the coenzyme. Single amino acid substitution, known to abolish the
      NADP+ binding, cancelled the calorimetric effect of the coenzyme. GAPN thermal
      inactivation was considerably decelerated in the presence of NADP+ showing that
      the apparent change in stability of the active centre can be the opposite to that
      of the whole protein molecule. NADP+ could also reactivate the inactive GAPN*
      species, obtained by the heating of the apoenzyme below the thermal denaturation
      transition temperature. These effects may reflect a mechanism that provides GAPN
      the sufficient flexibility for the earlier observed profound active site
      reorganizations required during the catalytic cycle. The elevated thermal
      stability of the apoenzyme may, in turn, be important for maintaining a constant
      level of active GAPN--an enzyme that is known to be crucial for the effective
      supply of the reducing equivalents in S. mutans and its ability to grow under
      aerobic conditions.

PMID- 24032675
TI  - Mast cells, glia and neuroinflammation: partners in crime?
AB  - Glia and microglia in particular elaborate pro-inflammatory molecules that play
      key roles in central nervous system (CNS) disorders from neuropathic pain and
      epilepsy to neurodegenerative diseases. Microglia respond also to pro
      inflammatory signals released from other non-neuronal cells, mainly those of
      immune origin such as mast cells. The latter are found in most tissues, are CNS
      resident, and traverse the blood-spinal cord and blood-brain barriers when
      barrier compromise results from CNS pathology. Growing evidence of mast cell-glia
      communication opens new perspectives for the development of therapies targeting
      neuroinflammation by differentially modulating activation of non-neuronal cells
      that normally control neuronal sensitization - both peripherally and centrally.
      Mast cells and glia possess endogenous homeostatic mechanisms/molecules that can
      be up-regulated as a result of tissue damage or stimulation of inflammatory
      responses. Such molecules include the N-acylethanolamine family. One such member,
      N-palmitoylethanolamine is proposed to have a key role in maintenance of cellular
      homeostasis in the face of external stressors provoking, for example,
      inflammation. N-Palmitoylethanolamine has proven efficacious in mast-cell
      mediated experimental models of acute and neurogenic inflammation. This review
      will provide an overview of recent progress relating to the pathobiology of
      neuroinflammation, the role of microglia, neuroimmune interactions involving mast
      cells and the possibility that mast cell-microglia cross-talk contributes to the
      exacerbation of acute symptoms of chronic neurodegenerative disease and
      accelerates disease progression, as well as promoting pain transmission pathways.
      We will conclude by considering the therapeutic potential of treating systemic
      inflammation or blockade of signalling pathways from the periphery to the brain
      in such settings.

PMID- 24032679
TI  - Unveiling the paradoxical nature of myelodysplastic syndromes (MDS): why
      hypercellular marrow strongly favors accelerated apoptosis.
AB  - The pathogenesis of bone marrow failure in myelodysplastic syndromes (MDS) is an
      unresolved mystery. MDS causes peripheral blood cytopenias and increased bone
      marrow cellularity. This apparent paradox has been interpreted as a sign of
      intramedullary destruction of a substantial portion of the developing
      hematopoietic cells by apoptosis. The present study aimed to delineate the exact
      mechanistic relationship between the bone marrow hypercellularity and the
      accelerated apoptosis in an N-ethyl-N-nitrosourea (ENU)-induced experimental MDS
      mouse model. The observations made so far clarify the quantitative and
      qualitative changes that occur in the bone marrow microenvironment through cell
      cycle analysis, especially involving the telomerase reverse transcriptase (TERT)
      and p53 expression patterns. The survival fate of the bone marrow cells were
      observed by measuring the expression level of some intracellular protein
      molecules like apoptosis signal-regulating kinase 1 (ASK-1), c-Jun N-terminal
      kinase (JNK), and cleaved caspase-3 of the extrinsic pathway toward apoptosis. We
      found myelodysplasia damage occurs within one or more multipotent progenitor
      populations resulting in uncontrolled cellular proliferation within the MDS bone
      marrow. Then, due to homeostatic balance, this high cellular burden is minimized
      by activating the apoptosis pathway. As a result, the peripheral blood suffers
      cellular deprivation. This study can throw some light on the mechanism of disease
      progression and also help to reveal the paradoxical nature of the disease.

PMID- 24032680
TI  - Clinorotation enhances autophagy in vascular endothelial cells.
AB  - Individuals exposed to extended periods of spaceflight or prolonged 6 degrees 
      head-down-tilt bed rest often suffer from health hazards represented by
      cardiovascular deconditioning. Many studies have reported that alterations in
      vascular endothelial cells contribute to cardiovascular dysfunction induced by
      microgravity. Autophagy, a lysosomal degradation pathway, serves an adaptive role
      for survival, differentiation, and development in cellular homeostasis, and can
      be triggered by various environmental stimuli. However, whether autophagy can be
      induced in endothelial cells by real or simulated microgravity remains to be
      determined. This study was designed to investigate the effects of simulated
      microgravity on the activation of autophagy in human umbilical vein endothelial
      cells (HUVECs). We report here that clinorotation, a simulated model of
      microgravity, enhances autophagosome formation, increases LC3 and beclin-1
      expression, and promotes the conversion of LC3-I to LC3-II in HUVECs. These
      results demonstrate that simulated microgravity for 48 h activates autophagy of
      vascular endothelial cells.

PMID- 24032681
TI  - Increased oxidative stress and decreased membrane fluidity in erythrocytes of CAD
      patients.
AB  - One of many risk factors for cardiovascular disease appears to be oxidative
      stress. To estimate possible changes in redox balance, membrane fluidity, and
      cholesterol level in erythrocytes was collected erythrocytes from patients
      diagnosed with coronary artery disease (CAD). The study included 20 patients with
      previous myocardial infarction occurring more than 6 months prior to the time of
      screening with low-density lipoprotein cholesterol (LDL-C) > 70 mg/dL and 21
      healthy controls. The following parameters were studied: catalase, glutathione
      peroxidase (GPx), superoxide dismutase (SOD), thiobarbituric acid reactive
      substrates (TBARS), sulfhydryl (SH) groups in membrane protein, total cholesterol
      level, and erythrocyte membrane fluidity. Our study showed an increase in the
      level of lipid peroxidation (13%) and total cholesterol (19%), and a decrease in
      membrane fluidity (14%) in the subsurface layers and in the deeper layers of
      erythrocyte membrane (7%) isolated from patients with CAD in comparison to
      healthy controls. A significant decrease in catalase (10%) and SOD (17%)
      activities were also observed. No changes in GPx activity or the level of SH
      groups were observed. Our study indicates that there are disorders in the
      antioxidant system as well as changes in the membrane structure of erythrocytes
      obtained from CAD patients.

PMID- 24032682
TI  - DNA damage induced by phenylalanine and its analogue p-chlorophenylalanine in
      blood and brain of rats subjected to a model of hyperphenylalaninemia.
AB  - Phenylketonuria (PKU) is a disease caused by a deficiency of phenylalanine
      hydroxylase (PAH), resulting in an accumulation of phenylalanine (Phe) in the
      brain tissue, cerebrospinal fluid, and other tissues of PKU patients. Considering
      that high levels of Phe are associated with neurological dysfunction and that the
      mechanisms underlying the neurotoxicity in PKU remain poorly understood, the main
      objective of this study was to investigate the in vivo and in vitro effects of
      Phe on DNA damage, as determined by the alkaline comet assay. The results showed
      that, compared to control group, the levels of DNA migration were significantly
      greater after acute administration of Phe, p-chlorophenylalanine (p-Cl-Phe, an
      inhibitor of PAH), or a combination thereof in cerebral cortex and blood,
      indicating DNA damage. These treatments also provoked increase of carbonyl
      content. Additionally, when Phe or p-Cl-Phe was present in the incubation medium,
      we observed an increase in the frequency and index of DNA damage in the cerebral
      cortex and blood, without affecting lactate dehydrogenase (LDH) release. Our in
      vitro and in vivo findings indicate that DNA damage occurs in the cerebral cortex
      and blood of rats receiving Phe, suggesting that this mechanism could be, at
      least in part, responsible for the neurological dysfunction in PKU patients. 

PMID- 24032683
TI  - Knockdown of prothymosin alpha leads to apoptosis and developmental defects in
      zebrafish embryos.
AB  - Prothymosin alpha (ProTalpha) is an abundant nuclear protein involved in cellular
      processes intricately linked to development, such as cell proliferation and
      apoptosis. Although it is known that ProTalpha inhibits the formation of
      apoptosome and blocks caspase-3 activity, its mechanism of function in the
      apoptotic machinery is still under investigation. We have studied the cellular
      role of ProTalpha by knocking down its expression in HeLa cells with small
      hairpin RNA (shRNA) in the absence of apoptotic stimuli. Flow cytometric analysis
      showed that the live cell population was significantly decreased with a
      concomitant increase of the apoptotic populations. To understand the
      physiological role of ProTalpha within the context of embryonic development, we
      knocked down the Ptmab zebrafish ortholog using 2 specific morpholino
      oligonucleotides. Ptmab morphants exhibited growth retardation, bended trunks,
      and curly tails. The frequency of occurrence of the phenotypic defects was
      increased in a morpholino dose-dependent manner. Co-injection of ptmaa mRNA with
      ptmab morpholino partially rescued the morphological defects. Immunostaining with
      the anti-phospho-histone H3 (pH3) antibody suggested that the abnormalities of
      Ptmab morphants could be due to defective cell proliferation that results in
      growth imbalances. TUNEL fluorescent labelling and Acridine Orange staining of
      the morphants showed high rates of cell death in the head and tail regions.
      Concomitantly, the active form of caspase-3 was detected in Ptmab morphants. Our
      data suggest a conserved anti-apoptotic role of ProTalpha between zebrafish and
      humans, and provide the first evidence that ProTalpha is important for early
      embryogenesis.

PMID- 24032684
TI  - Mycophenolic acid affects basic functions of human keratinocytes in the IMPDH
      dependent manner.
AB  - Clinical studies suggest that the immunosuppressant MPA is associated with
      impaired wound healing. It is believed that the main cause of impairment is the
      inhibition of inflammatory response. However, it is unknown whether MPA may
      directly affect epidermal cells. The aim of our study was to examine the direct
      influence of mycophenolic acid, the selective blocker of de novo purine
      synthesis, on human epidermal keratinocyte morphology, proliferation, motile
      activity, and differentiation in in vitro culture. The number of keratinocytes
      cultured in the presence of MPA was counted and cell motility was measured by a
      time-lapse computer-aided method. Cell morphology was determined by flow and
      image cytometry methods. Real-time RT-PCR analysis was employed to investigate
      the expression of markers of differentiation. We showed that MPA induces
      irreversible inhibition of cell proliferation, causes cell enlargement and
      impairs cell locomotion in a time-dependent manner. The level of expression of
      differentiation markers was significantly reduced by MPA treatment. All these
      effects were reversed by the addition of guanine. Our results indicated that MPA
      impairs basic functions of human skin keratinocytes via intracellular guanosine
      nucleotide depletion, which may be directly reflected in wound healing problems
      in patients treated with this immunosuppressant. 

PMID- 24032685
TI  - BDNF protects human vascular endothelial cells from TNFalpha-induced apoptosis.
AB  - Brain-derived neurotrophic factor (BDNF) enhances periodontal tissue
      regeneration. Tissue regeneration is characterized by inflammation that directs
      the quality of tissue repair. In this study, we investigated the anti-apoptotic
      effect of BDNF against the toxicity of tumor necrosis factor alpha (TNFalpha),
      which is known for its pro-apoptotic action in human microvascular endothelial
      cells (HMVECs). We demonstrate that BDNF attenuates TNFalpha-increased Annexin V
      positive cells, lactic dehydrogenase (LDH) release, and intercellular adhesion
      molecule 1 (ICAM-1) mRNA and cleaved caspase-3 expression. In addition,
      biochemical analyses indicate that TNFalpha increases phosphatase and tensin
      homolog (PTEN) expression; however, it decreases phosphorylated PTEN. BDNF did
      not affect PTEN expression, but it did increase the phosphorylation of PTEN. BDNF
      induced Akt phosphorylation was inhibited by TNFalpha. Terminal deoxynucleotidyl
      transferase (TdT) dUTP nick end labeling (TUNEL) assay showed that the PTEN
      inhibitor bpV(pic) rescues HMVECs from TNFalpha-induced apoptosis. In conclusion,
      BDNF protects HMVECs from toxicity of TNFalpha through the regulation of the
      PTEN/Akt pathway.

PMID- 24032686
TI  - Striatal cholinergic functional alterations in hypoxic neonatal rats: role of
      glucose, oxygen, and epinephrine resuscitation.
AB  - Molecular processes regulating cholinergic functions play an important role in
      the control of respiration under hypoxia. Cholinergic alterations and its further
      complications in respiration due to hypoxic insult in neonatal rats and the
      effect of glucose, oxygen, and epinephrine resuscitation was evaluated in the
      present study. Receptor binding and gene expression studies were done in the
      corpus striatum to analyse the changes in total muscarinic receptors, muscarinic
      M1, M2, M3 receptors, and the enzymes involved in acetylcholine metabolism,
      choline acetyltransferase and acetylcholinesterase. Neonatal hypoxia decreased
      total muscarinic receptors with reduced expression of muscarinic M1, M2, and M3
      receptor genes. The reduction in acetylcholine metabolism is indicated by the
      downregulated choline acetyltransferase and upregulated acetyl cholinesterase
      expression. These cholinergic disturbances were reversed to near control in
      glucose-resuscitated hypoxic neonates. The adverse effects of immediate
      oxygenation and epinephrine administration are also reported. The present
      findings points to the cholinergic alterations due to neonatal hypoxic shock and
      suggests a proper resuscitation method to ameliorate these striatal changes. 

PMID- 24032687
TI  - The role of caveolae in regulating calcitonin receptor-like receptor subcellular
      distribution in vascular smooth muscle cells.
AB  - To determine whether caveolae and caveolin-1 affect the distribution of
      calcitonin receptor-like receptors (CLR) in vascular smooth muscle cell (VSMC)
      membranes, we have used VSMCs cell line A10. We found that calcitonin gene
      related peptide (CGRP) reduced CLR protein in the VSMC membrane in a time
      dependent manner, which was dramatically decreased after 4 h CGRP treatment, and
      remained at a low level after 16 h. CGRP8-37 or beta-cyclodextrin (beta-CD)
      blocked this effect, without changing the total levels of CLR protein and mRNA in
      the cells. Co-immunoprecipitation experiments showed that CLR bound to caveolin-1
      in cell membrane fractions. Confocal laser microscopic studies confirmed this co
      localization relationship at the cell plasma membrane. Thus, our data indicate
      that the structural integrity of caveolae plays an important role in regulating
      subcellular distribution of CLR.

PMID- 24032688
TI  - Synthesis of the BCDE molecular fragment of azadiradione mediated by
      titanocene(III).
AB  - A practical, short, and diastereoselective synthesis of the azadiradione BCDE
      fragment from a readily available starting material is described. The key step
      was the titanocene(III)-promoted tandem cyclization of unsaturated epoxy nitrile.

PMID- 24032689
TI  - Quantitative sonoelastography of the uterine cervix by interposition of a
      synthetic reference material.
AB  - OBJECTIVE: To develop a reference material that allows quantitative elastography
      of the uterine cervix using the calculation of the approximate tissue stiffness
      expressed as Young's modulus (N/mm(2) ). Further, to test the elastography
      equipment on phantoms from a clinical perspective regarding the distance
      dependence and the influence of a heterogeneous material. DESIGN: Methodological
      study. SETTING: Aarhus University Hospital, Denmark. POPULATION: Six mid- and
      five full-term pregnant women. METHODS: Reference caps and phantoms with Young's
      moduli between 0.07 and 0.40 N/mm(2) were made of silicone and oil. By using
      reference caps, the approximate Young's moduli of the cervixes were calculated
      from strain ratios obtained by elastography. MAIN OUTCOME MEASURES: Approximate
      Young's modulus of the cervix. RESULTS: The recordings of the phantoms revealed
      that the calculation of the approximate Young's moduli became unreliable at
      distances above 10-15 mm from the transducer. This was further increased for a
      phantom which included a soft layer imitating the cervical canal. The approximate
      Young's modulus obtained from the anterior cervical lip was 0.08 N/mm(2) in mid
      term and 0.03 N/mm(2) in full-term pregnant women (Wilcoxon rank-sum test, p =
      0.01). CONCLUSION: The reference cap constitutes a promising tool for
      quantitative elastography of the anterior cervical lip. Figures obtained from the
      posterior cervical lip are less plausible due to the distance from the transducer
      and the heterogeneity introduced by the cervical canal. The method has the
      potential to be used to supplement cervical length assessment when evaluating
      women at risk of preterm delivery and when planning induction of labor.

PMID- 24032690
TI  - Activity descriptor identification for oxygen reduction on nonprecious
      electrocatalysts: linking surface science to coordination chemistry.
AB  - Developing nonprecious group metal based electrocatalysts for oxygen reduction is
      crucial for the commercial success of environmentally friendly energy conversion
      devices such as fuel cells and metal-air batteries. Despite recent progress,
      elegant bottom-up synthesis of nonprecious electrocatalysts (typically Fe-N(x)/C)
      is unavailable due to lack of fundamental understanding of molecular governing
      factors. Here, we elucidate the mechanistic origin of oxygen reduction on
      pyrolyzed nonprecious catalysts and identify an activity descriptor based on
      principles of surface science and coordination chemistry. A linear relationship,
      depicting the ascending portion of a volcano curve, is established between oxygen
      reduction turnover number and the Lewis basicity of graphitic carbon support
      (accessed via C 1s photoemission spectroscopy). Tuning electron
      donating/withdrawing capability of the carbon basal plane, conferred upon it by
      the delocalized pi-electrons, (i) causes a downshift of e(g)-orbitals (d(z(2)))
      thereby anodically shifting the metal ion's redox potential and (ii) optimizes
      the bond strength between the metal ion and adsorbed reaction intermediates
      thereby maximizing oxygen-reduction activity.

PMID- 24032691
TI  - Targeting IL-8 signalling to inhibit breast cancer stem cell activity.
AB  - Although survival from breast cancer has improved significantly over the past 20
      years, disease recurrence remains a significant clinical problem. The concept of
      stem-like cells in cancer has been gaining currency over the last decade or so,
      since evidence for stem cell activity in human leukaemia and solid tumours,
      including breast cancer, was first published. Evidence indicates that this sub
      population of cells, known as cancer stem-like cells (CSCs), is responsible for
      driving tumour formation and disease progression. In breast cancer, there is good
      evidence that CSCs are intrinsically resistant to conventional chemo-, radio- and
      endocrine therapies. By evading the effects of these treatments, CSCs are held
      culpable for disease recurrence. Hence, in order to improve treatment there is a
      need to develop CSC-targeted therapies. Interleukin-8 (IL-8), an inflammatory
      cytokine, is upregulated in breast cancer and associated with poor prognostic
      factors. Accumulating evidence demonstrates that IL-8, through its receptors
      CXCR1/2, is an important regulator of breast CSC activity. Inhibiting CXCR1/2
      signalling has proved efficacious in pre-clinical models of breast cancer
      providing a good rationale for targeting CXCR1/2 clinically. Here, we discuss the
      role of IL-8 in breast CSC regulation and development of novel therapies to
      target CXCR1/2 signalling in breast cancer. 

PMID- 24032692
TI  - Plasma-assisted combustion technology for NOx reduction in industrial burners.
AB  - Stronger regulations on nitrogen oxide (NOx) production have recently promoted
      the creation of a diverse array of technologies for NOx reduction, particularly
      within the combustion process, where reduction is least expensive. In this paper,
      we discuss a new combustion technology that can reduce NOx emissions within
      industrial burners to single-digit parts per million levels without employing
      exhaust gas recirculation or other NOx reduction mechanisms. This new technology
      uses a simple modification of commercial burners, such that they are able to
      perform plasma-assisted staged combustion without altering the outer
      configuration of the commercial reference burner. We embedded the first-stage
      combustor within the head of the commercial reference burner, where it operated
      as a reformer that could host a partial oxidation process, producing hydrogen
      rich reformate or synthesis gas product. The resulting hydrogen-rich flow then
      ignited and stabilized the combustion flame apart from the burner rim.
      Ultimately, the enhanced mixing and removal of hot spots with a widened flame
      area acted as the main mechanisms of NOx reduction. Because this plasma burner
      acted as a low NOx burner and was able to reduce NOx by more than half compared
      to the commercial reference burner, this methodology offers important cost
      effective possibilities for NOx reduction in industrial applications. 

PMID- 24032693
TI  - International survey on plasma transfusion practices in critically ill children.
AB  - BACKGROUND: Studies have shown heterogeneity in red blood cell transfusion
      practices. Although plasma transfusion is common in intensive care, there are no
      data on plasma transfusion practices in pediatric critical care units. STUDY
      DESIGN AND METHODS: A scenario-based survey was sent to 718 pediatric critical
      care physicians working in Europe, North America, Australia, and New Zealand.
      Respondents were asked to report their decisions regarding plasma transfusion
      practice with respect to four scenarios: pneumonia, septic shock, traumatic brain
      injury (TBI), and postoperative care after a Tetralogy of Fallot correction.
      RESULTS: The response rate was 187 of 718 (26%); half of the responders worked in
      North America. The proportion of physicians who transfused plasma to nonbleeding
      patients, solely based on abnormal international normalized ratio (INR), varied
      from 66% for pneumonia to 84% for TBI (p < 0.001). In such nonbleeding patients,
      the median INR threshold that would trigger plasma transfusion was 2.5 for
      pneumonia and septic shock patients and 2.0 for TBI and the cardiac postoperative
      patients (p < 0.001). Minor bleeding, minor surgery, insertion of a femoral line,
      hypotension, abnormal activated partial thromboplastin time, thrombocytopenia,
      and anemia levels were important determinants of plasma transfusion, whereas none
      of the respondents' demographic characteristics were important. CONCLUSION: More
      than two-thirds of responding pediatric critical care physicians prescribe plasma
      transfusions for nonbleeding critically ill children. Additionally, there is a
      significant variation in transfusion practice patterns with respect to plasma
      transfusion thresholds.

PMID- 24032694
TI  - Construction of vicinal all-carbon quaternary stereocenters by catalytic
      asymmetric alkylation reaction of 3-bromooxindoles with 3-substituted indoles:
      total synthesis of (+)-perophoramidine.
AB  - Highly congested vicinal all-carbon quaternary stereocenters were generated via
      catalytic asymmetric alkylation reaction of 3-bromooxindoles with 3-substituted
      indoles. These catalytic reactions proceeded in excellent yields with a broad
      scope on either reaction partner, and with outstanding diastereo- and
      enantiocontrol. The newly developed method led to the total synthesis of (+)
      perophoramidine in a highly efficient manner. 

PMID- 24032695
TI  - Patch testing for allergic contact dermatitis to cigarettes: smoked/unsmoked
      components and formaldehyde factors.
AB  - A patient with hand dermatitis reported that switching her smoking hand resulted
      in reduced symptoms. When allergy to cigarettes is suspected the literature
      supports standard allergy testing as well as testing the individual components of
      cigarettes. Initial standard patch testing revealed an allergy to formaldehyde
      and the formaldehyde releasing agent, quaternium-15. The patient did not react to
      her usual roll-your-own cigarette components but reacted to the smoked filter
      paper of a particular brand of cigarette she frequently borrowed from a friend.
      Possible explanations include either a variation of ingredients between
      cigarettes that alters the formaldehyde concentration or another unidentified
      allergen in the branded cigarette causing allergic contact dermatitis. 

PMID- 24032696
TI  - A technique to identify core journals for neurosurgery using citation scatter
      analysis and the Bradford distribution across neurosurgery journals.
AB  - OBJECT: The volume of scientific literature doubles approximately every 7 years.
      The coverage of this literature provided by online compendia is variable and
      incomplete. It would hence be useful to identify "core" journals in any field and
      validate whether the h index and impact factor truly identify the core journals
      in every subject. The core journals in every medical specialty would be those
      that provide a current and comprehensive coverage of the science in that
      specialty. Identifying these journals would make it possible for individual
      physicians to keep abreast of research and clinical progress. METHODS: The top 10
      neurosurgical journals (on the basis of impact factor and h index) were selected.
      A database of all articles cited in the reference lists of papers published in
      issues of these journals published in the first quarter of 2012 was generated.
      The journals were ranked based on the number of papers cited from each. This
      citation rank list was compared with the h index and impact factor rank lists.
      The rank list was also examined to see if the concept of core journals could be
      validated for neurosurgical literature using Bradford's law. RESULTS: A total of
      22,850 papers spread across 2522 journals were cited in neurosurgical literature
      over 3 months. Although the top 10 journals were the same, irrespective of
      ranking criterion (h index, impact factor, citation ranking), the 3 rank lists
      were not congruent. The top 25% of cited articles obeyed the Bradford
      distribution; beyond this, there was a zone of increased scatter. Six core
      journals were identified for neurosurgery. CONCLUSIONS: The core journals for
      neurosurgery were identified to be Journal of Neurosurgery, Neurosurgery, Spine,
      Acta Neurochirurgica, Stroke, and Journal of Neurotrauma. A list of core journals
      could similarly be generated for every subject. This would facilitate a focused
      reading to keep abreast of current knowledge. Collated across specialties, these
      journals could depict the current status of medical science.

PMID- 24032697
TI  - Posterior inferior cerebellar artery aneurysms.

PMID- 24032698
TI  - Medial temporal epilepsy.

PMID- 24032699
TI  - Neurosurgery in the Byzantine Empire: the contributions of Paul of Aegina (625
      690 AD).
AB  - Paul of Aegina (625-690 AD) was born on the island of Aegina and was one of the
      most prominent physician-writers of the Byzantine Empire. His work Epitome of
      Medicine, comprised of 7 books, was a comprehensive compendium of the medical and
      surgical knowledge of his time and was subsequently translated into multiple
      languages. Paul of Aegina made valuable contributions to neurosurgical subjects
      and described procedures for the treatment of nerve injuries, hydrocephalus, and
      fractures of the skull and spine. His work combined the ancient knowledge of
      Hippocrates and Galen with contemporary medical observations and served as a
      bridge between Byzantine and Arabic medicine. He is considered to be one of the
      great ancient Greek medical writers and his work has influenced the subsequent
      evolution of Western European and Arab medicine. This paper provides an account
      of his contribution to the management of neurosurgical pathologies during the
      Byzantine era, as described in his medical compendium, Epitome of Medicine. 

PMID- 24032700
TI  - Core journals.

PMID- 24032701
TI  - Predicting inpatient complications from cerebral aneurysm clipping: the
      Nationwide Inpatient Sample 2005-2009.
AB  - OBJECT: Precise delineation of individualized risks of morbidity and mortality is
      crucial in decision making in cerebrovascular neurosurgery. The authors attempted
      to create a predictive model of complications in patients undergoing cerebral
      aneurysm clipping (CAC). METHODS: The authors performed a retrospective cohort
      study of patients who had undergone CAC in the period from 2005 to 2009 and were
      registered in the Nationwide Inpatient Sample (NIS) database. A model for outcome
      prediction based on preoperative individual patient characteristics was
      developed. RESULTS: Of the 7651 patients in the NIS who underwent CAC, 3682
      (48.1%) had presented with unruptured aneurysms and 3969 (51.9%) with
      subarachnoid hemorrhage. The respective inpatient postoperative risks for death,
      unfavorable discharge, stroke, treated hydrocephalus, cardiac complications, deep
      vein thrombosis, pulmonary embolism, and acute renal failure were 0.7%, 15.3%,
      5.3%, 1.5%, 1.3%, 0.6%, 2.0%, and 0.1% for those with unruptured aneurysms and
      11.5%, 52.8%, 5.5%, 39.2%, 1.7%, 2.8%, 2.7%, and 0.8% for those with ruptured
      aneurysms. Multivariate analysis identified risk factors independently associated
      with the above outcomes. A validated model for outcome prediction based on
      individual patient characteristics was developed. The accuracy of the model was
      estimated using the area under the receiver operating characteristic curve, and
      it was found to have good discrimination. CONCLUSIONS: The featured model can
      provide individualized estimates of the risks of postoperative complications
      based on preoperative conditions and can potentially be used as an adjunct in
      decision making in cerebrovascular neurosurgery.

PMID- 24032702
TI  - The incidence of complications in elective cranial neurosurgery associated with
      dural closure material.
AB  - OBJECT: Dural closure with synthetic grafts has been suggested to contribute to
      the incidence of infection and CSF leak. The objective of this study was to
      assess the contribution of choice of dural closure material, as well as other
      factors, to the incidence of infection and CSF leak. METHODS: A retrospective,
      consecutive cohort study of adult patients undergoing elective craniotomy was
      established between April 2010 and March 2011 at a single center. Exclusion
      criteria consisted of trauma, bur hole placement alone, and temporary CSF fluid
      diversion. RESULTS: Three hundred ninety-nine patients were included (mean follow
      up 396.6 days). Nonautologous (synthetic) dural substitute was more likely to be
      used (n = 106) in cases of reoperation (p = 0.001). Seventeen patients developed
      a surgical site infection and 12 patients developed a CSF leak. Multivariate
      logistic regression modeling identified estimated blood loss (OR 1.002, 95% CI
      1.001-1.003; p < 0.001) and cigarette smoking (OR 2.198, 95% CI 1.109-4.238; p =
      0.019) as significant predictors of infection. Synthetic dural graft was not a
      predictor of infection in multivariate analysis. Infratentorial surgery (OR
      4.348, 95% CI 1.234-16.722; p = 0.024) and more than 8 days of postoperative
      corticosteroid treatment (OR 3.886, 95% CI 1.052-16.607; p = 0.048) were
      significant predictors for the development of CSF leak. Synthetic dural graft was
      associated with a lower likelihood of CSF leak (OR 0.072, 95% CI 0.003-0.552; p =
      0.036). CONCLUSIONS: The use of synthetic dural closure material is not
      associated with surgical site infection and is associated with a reduced
      incidence of CSF leak. Modifiable risk factors exist for craniotomy complications
      that warrant vigilance and further study.

PMID- 24032703
TI  - Magnetic resonance imaging validation of pituitary gland compression and
      distortion by typical sellar pathology.
AB  - OBJECT: Identification of the normal pituitary gland is an important component of
      presurgical planning, defining many aspects of the surgical approach and
      facilitating normal gland preservation. Magnetic resonance imaging is a proven
      imaging modality for optimal soft-tissue contrast discrimination in the brain.
      This study is designed to validate the accuracy of localization of the normal
      pituitary gland with MRI in a cohort of surgical patients with pituitary mass
      lesions, and to evaluate for correlation between presurgical pituitary hormone
      values and pituitary gland characteristics on neuroimaging. METHODS: Fifty-eight
      consecutive patients with pituitary mass lesions were included in the study.
      Anterior pituitary hormone levels were measured preoperatively in all patients.
      Video recordings from the endoscopic or microscopic surgical procedures were
      available for evaluation in 47 cases. Intraoperative identification of the normal
      gland was possible in 43 of 58 cases. Retrospective MR images were reviewed in a
      blinded fashion for the 43 cases, emphasizing the position of the normal gland
      and the extent of compression and displacement by the lesion. RESULTS: There was
      excellent agreement between imaging and surgery in 84% of the cases for normal
      gland localization, and in 70% for compression or noncompression of the normal
      gland. There was no consistent correlation between preoperative pituitary
      dysfunction and pituitary gland localization on imaging, gland identification
      during surgery, or pituitary gland compression. CONCLUSIONS: Magnetic resonance
      imaging proved to be accurate in identifying the normal gland in patients with
      pituitary mass lesions, and was useful for preoperative surgical planning.

PMID- 24032704
TI  - Assessment of the rate of spinal motor axon regeneration by choline
      acetyltransferase immunohistochemistry following sciatic nerve crush injury in
      mice.
AB  - OBJECT: The purpose of this study was to examine whether choline
      acetyltransferase (ChAT) staining can be used for assessing the rate of motor
      neuron regeneration at an early phase of axon outgrowth. METHODS: The authors
      developed a new sciatic nerve crush model in adult mice. In this model, in
      addition to performing a sciatic nerve crush injury, the authors excised the
      ipsilateral lumbar L3-6 dorsal root ganglion (DRG), which resulted in
      degeneration of the sensory fibers entering into the sciatic nerve. Crushed nerve
      sections obtained at Day 3 or Day 7 postinjury were analyzed by means of
      immunostaining. RESULTS: The immunostaining showed that ChAT, a motor axon
      specific antigen, was totally co-localized with growth-associated protein 43 (GAP
      43), which is expressed in regenerating nerves and transported into growth cones.
      CONCLUSIONS: Our results suggest that measuring the length of motor axon
      outgrowth by ChAT immunostaining is reliable. ChAT staining provides a more
      convenient method for evaluating the rate of motor axon outgrowth in a mixed
      nerve.

PMID- 24032705
TI  - Selective amygdalohippocampectomy versus anterior temporal lobectomy in the
      management of mesial temporal lobe epilepsy: a meta-analysis of comparative
      studies.
AB  - OBJECT: Whether selective amygdalohippocampectomy (SelAH) has similar seizure
      outcomes and better neuropsychological outcomes compared with anterior temporal
      lobectomy (ATL) is a matter of debate. The aim of this study was to compare the 2
      types of surgery with respect to seizure outcomes and changes in IQ scores.
      METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant
      studies published between January 1990 and September 2012. Studies comparing
      SelAH and ATL with respect to seizure and intelligence outcomes were included.
      Two reviewers assessed the quality of the included studies and independently
      extracted the data. Odds ratios and standardized mean deviations with 95%
      confidence intervals were used to compare pooled proportions of freedom from
      seizures and changes in IQ scores between the SelAH and ATL groups. RESULTS:
      Three prospective and 10 retrospective studies were identified involving 745 and
      766 patients who underwent SelAH and ATL, respectively. The meta-analysis
      demonstrated a statistically significant reduction in the odds of seizure freedom
      for patients who underwent SelAH compared with those who underwent ATL (OR 0.65
      [95% CI 0.51-0.82], p = 0.0005). The differences between the changes in all IQ
      scores after the 2 types of surgery were not statistically significant,
      regardless of the side of resection. CONCLUSIONS: Selective
      amygdalohippocampectomy statistically reduced the odds of being seizure free
      compared with ATL, but the clinical significance of this reduction needs to be
      further validated by well-designed randomized trials. Selective
      amygdalohippocampectomy did not have better outcomes than ATL with respect to
      intelligence.

PMID- 24032706
TI  - Low-dose intravenous heparin infusion in patients with aneurysmal subarachnoid
      hemorrhage: a preliminary assessment.
AB  - OBJECT: Aneurysmal subarachnoid hemorrhage (aSAH) predisposes to delayed
      neurological deficits, including stroke and cognitive and neuropsychological
      abnormalities. Heparin is a pleiotropic drug that antagonizes many of the
      pathophysiological mechanisms implicated in secondary brain injury after aSAH.
      METHODS: The authors performed a retrospective analysis in 86 consecutive
      patients with Fisher Grade 3 aSAH due to rupture of a supratentorial aneurysm who
      presented within 36 hours and were treated by surgical clipping within 48 hours
      of their ictus. Forty-three patients were managed postoperatively with a low-dose
      intravenous heparin infusion (Maryland low-dose intravenous heparin infusion
      protocol: 8 U/kg/hr progressing over 36 hours to 10 U/kg/hr) beginning 12 hours
      after surgery and continuing until Day 14 after the ictus. Forty-three control
      patients received conventional subcutaneous heparin twice daily as deep vein
      thrombosis prophylaxis. RESULTS: Patients in the 2 groups were balanced in terms
      of baseline characteristics. In the heparin group, activated partial
      thromboplastin times were normal to mildly elevated; no clinically significant
      hemorrhages or instances of heparin-induced thrombocytopenia or deep vein
      thrombosis were encountered. In the control group, the incidence of clinical
      vasospasm requiring rescue therapy (induced hypertension, selective intraarterial
      verapamil, and angioplasty) was 20 (47%) of 43 patients, and 9 (21%) of 43
      patients experienced a delayed infarct on CT scanning. In the heparin group, the
      incidence of clinical vasospasm requiring rescue therapy was 9% (4 of 43, p =
      0.0002), and no patient suffered a delayed infarct (p = 0.003). CONCLUSIONS: In
      patients with Fisher Grade 3 aSAH whose aneurysm is secured, postprocedure use of
      a low-dose intravenous heparin infusion may be safe and beneficial.

PMID- 24032707
TI  - Intracranial biomechanics following cortical contusion in live rats.
AB  - OBJECT: The goal of this study was to examine the mechanical properties of living
      rat intracranial contents and corresponding brain structural alterations
      following parietal cerebral cortex contusion. METHODS: After being anesthetized,
      young adult rats were subjected to parietal craniotomy followed by cortical
      contusion using a calibrated weight-drop method. Magnetic resonance imaging was
      used to visualize the contusion. At the site of contusion, instrumented force
      controlled indentation was performed 2 hours to 21 days later on the intact dural
      surface. The force-deformation (stress-strain) relationship was used to calculate
      elastic (indentation modulus) and strain changes over time, and constant hold or
      cyclic stress was used to evaluate viscoelastic deformation. These measurements
      were followed by histological studies. RESULTS: At contusion sites, the
      indentation modulus was significantly decreased at 1-3 days and tended to be
      above control values at 21 days. Multicycle indentation showed that the brain
      tended to accumulate more strain (an indicator of viscosity) by 1 day after the
      contusion. Imaging and histological studies showed local edema and hemorrhage at
      6 hours to 3 days and accumulation of reactive astrocytes, which began at 3 days
      and was pronounced by 21 days. CONCLUSIONS: The viscoelastic properties of living
      rat brain change following contusion. Initially, edema and tissue necrosis occur,
      and the brain becomes less elastic and less viscous. Later, along with undergoing
      reactive astroglial changes, the brain tends to become stiffer than normal. These
      quantitative data, which are related to the physical changes in the brain
      following trauma and which reflect subjective impressions upon palpation, will be
      useful for understanding emerging diagnostic tools such as magnetic resonance
      elastography.

PMID- 24032708
TI  - Occipital lobe.

PMID- 24032709
TI  - Effects of exercise on stress-induced changes of norepinephrine and serotonin in
      rat hippocampus.
AB  - Exercise is beneficial to brain and can attenuate stress-induced hippocampal
      damages. However, the details involved monoamine neurotransmitter in exercise to
      counteract stress have not been well elucidated. The aim of this study was to
      examine exercise-induced responses of the norepinephrine (NE) and serotonin (5
      HT) systems in counteracting stress-induced hippocampal damages. Rats were
      divided into exercise (four weeks of voluntary wheel running), stress (three
      weeks of restraint stress), exercise-stress (three weeks of stress following four
      weeks of exercise), and control groups. Levels of NE and 5-HT were detected with
      high-performance liquid chromatography (HPLC), mRNA expression was detected with
      real-time fluorescence quantitative reverse transcription polymerase reaction (FQ
      RT-PCR) and proteins associated with 5-HT1Alpha receptors (5-HT1Alpha-R) and
      beta2-adrenergic receptors (beta2-AR) were analyzed by western blotting. 5-HT
      levels were highest (P < 0.01) in the exercised group, lowest (P < 0.05) in the
      stressed rats, and were similar (P = 0.065) in stressed and exercise-stressed
      rats. NE levels were highest (P < 0.01) in the exercised group, and higher in the
      exercise-stressed than the stressed rats (P < 0.01). 5-HT1A-R mRNA expression was
      highest (P < 0.01) in the exercised group, lowest in the stressed group. The 5
      HT1Alpha-R protein expression changed in the same tendency as its mRNA levels.
      The beta2-AR mRNA was highest in exercised rats (P < 0.05), and its protein
      expression was higher in the exercised and exercise-stress rats than in the
      control and stress rats (P < 0.05). In conclusion, norepinephrine may represent
      endophenotypic features of exercise states. Serotonin levels may be more
      susceptible to stress and responsible for deleterious stress-induced effects.
      Norepinephrine and serotonin may both contribute to counteraction of stress
      induced hippocampal damages of physical exercises. 

PMID- 24032710
TI  - Herbal haemorrhoidal cream for haemorrhoids.
AB  - Although hemorrhoids are one of the most common diseases in the world, the exact
      etiology underlying the development of hemorrhoids is not clear. Many different
      ointments are currently used to treat hemorrhoids; however, there is little
      evidence of the efficacy of these treatments to support their use. The aim of
      this study was to compare different herbal creams used for the treatment of
      hemorrhoids. Twenty-eight male Wistar albino rats, 6-8 weeks old and weighing 160
      180 g, were used in this study as 1-control, 2-croton oil, 3-croton oil+fig
      leaves+artichoke leaves+walnut husks and 4-croton oil+fig leaves+artichoke
      leaves+walnut husks+horse chestnut fruit. After 3 days of croton oil application,
      rats were treated with 0.1 ml of cream or saline twice a day for 15 days by
      syringe. Tissue and blood samples were collected for histological,
      immunohistochemical and biochemical studies. Statistical significance was
      determined using one-way ANOVA followed by Tukey's multiple comparison tests.
      Croton oil administration resulted in severe inflammation. The third group showed
      partial improvement in inflammation; however, the greatest degree of improvement
      was seen in the fourth group, and some recovered areas were observed.
      Myeloperoxidase immunoreactivity was found to be decreased in the third and
      fourth groups compared to the second group. Additionally, biochemical analyses
      (Myeloperoxidase, Malondyaldehyde, nitrate/nitrite and nitrotyrosine levels and
      Superoxide Dismutase activity) were in agreement with the histological and
      immunohistochemical results. In conclusion, croton oil causes inflammation in the
      anal area and results in hemorrhoids. Treatment with our herbal hemorrhoid creams
      demonstrated anti-inflammatory and anti-oxidant effects in this model. 

PMID- 24032711
TI  - The joint effect of hOGG1 genotype and smoking habit on endometriosis in Taiwan.
AB  - This study has two aims: [1] to evaluate the association between hOGG1 genotypic
      polymorphism and endometriosis risk, and [2] to investigate the joint effects of
      hOGG1 genotype and smoking habit on endometriosis susceptibility in Taiwan. For
      this purpose, the well-known polymorphic variants of hOGG1, codon 326, was
      genotyped and analyzed of its association with the risk of endometriosis. In
      total, 153 patients with endometriosis and 636 non-endometriosis healthy controls
      were recruited and genotyped. The methodology for genotyping is polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP). Pearson's Chi
      square test was performed to compare the distributions of the genotypes between
      case and control groups. The results showed that the hOGG1 codon 326 genotypes
      were not differently distributed between the endometriosis and non-endometriosis
      control groups in both genotypic (P = 0.6212) and allelic (P = 0.4006) frequency
      analysis. We have further analyzed the genotypic-smoking joint effects on
      endometriosis risk and found an obvious interaction between hOGG1 codon 326
      genotypes and smoking status. The hOGG1 codon 326 genotypes were increased in
      endometriosis risk only in the smoker groups (P = 0.0061), but not in the non
      chewer group (P = 0.0648). Our results provide the evidence that the hOGG1 codon
      326 genotype may have a joint effect with smoking on the development of
      endometriosis. 

PMID- 24032712
TI  - Functional connectivity changes during consolidation of inhibitory avoidance
      memory in rats: a manganese-enhanced MRI study.
AB  - Consolidation of memory involves transfer of encoded information into a durable
      neural representation, but how this is transacted in the nervous system remains
      elusive. It has been proposed that memory consolidation is subserved by formation
      of a cell assembly due to coincidence of pre- and post-synaptic activity therein
      after learning. To capture such off-line changes, manganese-enhanced magnetic
      resonance imaging (MEMRI) was used to trace brain activity during the memory
      consolidation period. Male Wistar rats were trained on the one-trial inhibitory
      avoidance task and received intraventricular infusion of manganese ion shortly
      after training. The MEMRI taken 1 day later showed that brain areas including the
      prelimbic, insular and anterior pirifrom cortices of the learning group had
      significantly lower memory-related MEMRI signal than those of the control group.
      The functional network was revealed by correlating the MEMRI signals among
      regions followed by graph theoretical analysis. Learning sculpted the non
      discriminative connectivity among many brain regions in the controls into a
      network in the trained rats with selected connectivity among regions implicated
      in inhibitory avoidance learning. The network could be organized into three
      clusters presumably subserving different functions. The results suggest that the
      brain prunes excessive functional connectivity in a cell assembly to consolidate
      new memory. 

PMID- 24032713
TI  - Histone trimethylation of the p53 gene by expression of a constitutively active
      prolactin receptor in prostate cancer cells.
AB  - Prolactin (PRL) is a pituitary polypeptide hormone characterized by multiple
      biological actions including stimulation of growth in the prostate, breast and
      ovarian epithelial cells. A sizable body of reports has presented evidences to
      indicate the involvement of PRL in the pathogenic process of cancers of the
      reproductive system, such as prostate and breast cancers. PRL exerts its effects
      by dimerizing its receptor (PRLR) on the plasma membrane, and initiating cellular
      Jak-Stat signal pathway. We have previously cloned from prostate cancer cells a
      natural variant of PRLR in which the S2 subdomain of the extracellular domain is
      missing (DeltaS2). Our preliminary data showed that DeltaS2 PRLR was able to
      dimerize and to constitutively activate the beta-casein promoter (in the absence
      of its ligand, PRL) in breast and prostate epithelial cells. Enhancer of zeste
      homologue 2 (EZH2), an important histone-modifying enzyme, is able to
      trimethylate histone 3 on lysine 27 (H3K27Me3), consequently leading to gene
      silencing, especially silencing of tumor suppressor genes such as p53. We
      hypothesized that DeltaS2 PRLR played an important pathogenic role in prostate
      cancer through, at least partly, alterations in the expression of EZH2 and the
      trimethylation of histone 3 on lysine 27. In the present study, overexpression of
      DeltaS2 PRLR in prostate epithelial cells was achieved by infection with an
      adenoviral vector carrying the cDNA. The viable cell number overexpressing
      DeltaS2 PRLR was assessed using MTS reagent. Western blot, chromatin
      immunoprecipitation (ChIP) assay and acid histone extraction were applied to
      detect expression of EZH2 as well as trimethylation of histone 3, respectively.
      In prostate epithelial cells, overexpression of DeltaS2 PRLR increased the levels
      of EZH2 methyltransferase mRNA and protein, induced EZH2 methyltransferase
      recruitment to chromatin, increased the trimethylation of histone 3 on lysine 27,
      and decreased expression of the p53 gene. We concluded that DeltaS2 PRLR plays an
      important pathogenic role in prostate cancer through epigenetic covalent
      modification leading to chromatin remodeling. Hypertrimethylation on H3K27 of the
      p53 gene promoter region due to elevated expression of DeltaS2 PRLR by
      alternative splicing of the pre-mRNA in its full-length form might serve as a new
      mechanism underlying human prostate cancer. 

PMID- 24032714
TI  - Role of neuronal nitric oxide synthase in the cardiac ischemia reperfusion in
      mice.
AB  - Several studies have demonstrated the role of endothelial and inducible nitric
      oxide synthase in cardiac ischemia reperfusion(IR). However, the role of neuronal
      nitric oxide synthase (nNOS) in IR is still controversial. The present study was
      designed to explore the possible involvement of nNOS in cardiac IR. nNOS-/-
      knockout (KO) and wild type C57 (WT) mice were subjected to 45 min of ischemia by
      left descending branch of coronary artery ligation followed by 3 h reperfusion,
      which plasma was collected for creatine kinase (CK) and lactate dehydrogenase
      (LDH) measurements, terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling (TUNEL) staining and measurements of activities of caspase-3, -8, -9,
      phospho-p38, -ERK, -JNK mitogen-activated protein kinase (MAPK) and phospho-nNOS,
      phospho-eNOS and iNOS. IR induced cardiac tissue apoptosis by increases of TUNEL
      staining and activities of caspase-3, -8, and -9, accompanied with increase of CK
      and LDH concentration and phosphorylation of p38, ERK and JNK MAPK and phospho
      nNOS, phospho-eNOS and iNOS in both mouse strains. However, IR induced increases
      of TUNEL staining and activities of caspase-3, -8 and -9, and CK and LDH
      concentrations and activation of p38 MAPK were markedly lower in KO mice compared
      with WT mice. But the phosphorylation of eNOS was significantly higher compared
      with WT IR group (P < 0.05). The data obtained suggest that nNOS exacerbates IR
      induced injury maybe involving p38 MAPK activation. 

PMID- 24032715
TI  - Effects of 3, 5, 3'-triiodothyronine (t3) and follicle stimulating hormone on
      apoptosis and proliferation of rat ovarian granulosa cells.
AB  - Thyroid hormone (TH) is important for normal reproductive functions and
      dysregulation of TH support is associated with reproductive disorders. We have
      previously reported that 3,5,3'-triiodothyronine (T3) increases follicle
      stimulating hormone (FSH)-induced preantral follicle growth in vitro. Interaction
      of hormones with apoptosis and proliferation of granulosa cells is poorly
      understood. The present study investigated the role and the mechanism of T3
      and/or FSH on granulosa cell apoptosis and proliferation. Granulosa cells
      harvested from DES-primed immature rats were exposed to T3 (1 nM) and/or FSH (100
      ng/ml) for 24-48 h. We demonstrated by TUNEL assays that the hormones prevented
      cells from C8-ceramide-induced apoptosis. The Src/PI3K/Akt pathway was involved
      in the regulation of granulosa cell survival. While ineffective alone, T3
      significantly enhanced the proliferating cell nuclear antigen (PCNA) content of
      FSH-induced granulosa cells, consistent with the cell number pattern after
      treatment. Moreover, the action of the hormones on cell proliferation was also
      shown to be mediated by the Src/PI3K/Akt pathway. Taken together, these results
      suggest that T3 potentiates the cell survival action of FSH through inhibiting
      cell apoptosis and promoting cell proliferation. Moreover, the protective and
      survival effects of hormones are mediated by the activation of Src/PI3K/Akt
      pathway. 

PMID- 24032716
TI  - Effect of balance training on postural balance control and risk of fall in
      children with diplegic cerebral palsy.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of balance
      training on postural control and fall risk in children with diplegic cerebral
      palsy. METHODS: Thirty spastic diplegic cerebral palsied children (10-12 years)
      were included in this study. Children were randomly assigned into two equal-sized
      groups: control and study groups. Participants in both groups received a
      traditional physical therapy exercise program. The study group additionally
      received balance training on the Biodex balance system. Treatment was provided 30
      min/d, 3 d/week for 3 successive months. To evaluate the limit of stability and
      fall risk, participated children received baseline and post-treatment assessments
      using the Biodex balance system. Overall directional control, total time to
      complete the test, overall stability index of the fall risk test and total score
      of the pediatric balance scale were measured. RESULTS: Children in both groups
      showed significant improvements in the mean values of all measured variables post
      treatment (p < 0.05). The results also showed significantly better improvement in
      the measured parameters for the study group, as compared to the control group (p
      < 0.05). CONCLUSION: Balance training on Biodex system is a useful tool that can
      be used in improving postural balance control in children with diplegic cerebral
      palsy.

PMID- 24032717
TI  - Assessing leaf photoprotective mechanisms using terrestrial LiDAR: towards
      mapping canopy photosynthetic performance in three dimensions.
AB  - Terrestrial laser scanning (TLS) data allow spatially explicit (x, y, z) laser
      return intensities to be recorded throughout a plant canopy, which could
      considerably improve our understanding of how physiological processes vary in
      three-dimensional space. However, the utility of TLS data for the quantification
      of plant physiological properties remains largely unexplored. Here, we test
      whether the laser return intensity of green (532-nm) TLS correlates with changes
      in the de-epoxidation state of the xanthophyll cycle and photoprotective non
      photochemical quenching (NPQ), and compare the ability of TLS to quantify these
      parameters with the passively measured photochemical reflectance index (PRI). We
      exposed leaves from five plant species to increasing light intensities to induce
      NPQ and de-epoxidation of violaxanthin (V) to antheraxanthin (A) and zeaxanthin
      (Z). At each light intensity, the green laser return intensity (GLRI), narrowband
      spectral reflectance, chlorophyll fluorescence emission and xanthophyll cycle
      pigment composition were recorded. Strong relationships between both predictor
      variables (GLRI, PRI) and both explanatory variables (NPQ, xanthophyll cycle de
      epoxidation) were observed. GLRI holds promise to provide detailed (mm)
      information about plant physiological status to improve our understanding of the
      patterns and mechanisms driving foliar photoprotection. We discuss the potential
      for scaling these laboratory data to three-dimensional canopy space. 

PMID- 24032718
TI  - Intravenous nicotine injection induces rapid, experience-dependent sensitization
      of glutamate release in the ventral tegmental area and nucleus accumbens.
AB  - Although numerous data suggest that glutamate (GLU) is involved in mediating the
      neural effects of nicotine, direct data on nicotine-induced changes in GLU
      release are still lacking. Here, we used high-speed amperometry with enzyme-based
      GLU and enzyme-free GLU-null biosensors to examine changes in extracellular GLU
      levels in the ventral tegmental area (VTA) and nucleus accumbens shell (NAcc)
      induced by intravenous nicotine in a low, behaviorally active dose (30 MUg/kg) in
      freely moving rats. Using this approach, we found that the initial nicotine
      injection in drug-naive conditions induces rapid, transient, and relatively small
      GLU release (~ 90 nM; latency ~ 15 s, duration ~ 60 s) that is correlative in the
      VTA and NAcc. Following subsequent nicotine injections within the same session,
      this phasic GLU release was supplemented by stronger tonic increases in GLU
      levels (100-300 nM) that paralleled increases in drug-induced locomotor
      activation. GLU responses induced by repeated nicotine injections were more
      phasic and stronger in the NAcc than in VTA. Therefore, GLU is phasically
      released within the brain's reinforcement circuit following intravenous nicotine
      administration. Robust enhancement of nicotine-induced GLU responses following
      repeated injections suggests this change as an important mediator of sensitized
      behavioral and neural effects of nicotine. By using high-speed amperometry with
      glutamate (GLU) biosensors, we show that i.v. nicotine at a low, behaviorally
      relevant dose induces rapid GLU release in the NAcc and VTA that is enhanced
      following repeated drug injections. This is the first study reporting second
      scale fluctuations in extracellular GLU levels induced by nicotine in two
      critical structures of the motivation-reinforcement circuit and rapid
      sensitization of GLU responses coupled with locomotor sensitization.

PMID- 24032719
TI  - Serious Hazards of Transfusion (SHOT) haemovigilance and progress is improving
      transfusion safety.
AB  - The Serious Hazards of Transfusion (SHOT) UK confidential haemovigilance
      reporting scheme began in 1996. Over the 16 years of reporting, the evidence
      gathered has prompted changes in transfusion practice from the selection and
      management of donors to changes in hospital practice, particularly better
      education and training. However, half or more reports relate to errors in the
      transfusion process despite the introduction of several measures to improve
      practice. Transfusion in the UK is very safe: 2.9 million components were issued
      in 2012, and very few deaths are related to transfusion. The risk of death from
      transfusion as estimated from SHOT data in 2012 is 1 in 322,580 components issued
      and for major morbidity, 1 in 21,413 components issued; the risk of transfusion
      transmitted infection is much lower. Acute transfusion reactions and transfusion
      associated circulatory overload carry the highest risk for morbidity and death.
      The high rate of participation in SHOT by National Health Service organizations,
      99.5%, is encouraging. Despite the very useful information gained about
      transfusion reactions, the main risks remain human factors. The recommendations
      on reduction of errors through a 'back to basics' approach from the first annual
      SHOT report remain absolutely relevant today.

PMID- 24032720
TI  - r-Shaped hybrid nanogenerator with enhanced piezoelectricity.
AB  - Piezoelectric and triboelectric nanogenerators (NGs) have been proposed in the
      past few years to effectively harvest mechanical energy from the environment.
      Here, a polydimethylsiloxane (PDMS) layer is placed under the aluminum electrode
      of polyvinylidene fluoride (PVDF), thus forming an r-shaped hybrid NG.
      Micro/nanostructures have been fabricated on the PDMS surface and the aluminum
      electrodes of PVDF to enhance the output performance. Power densities of the
      piezoelectric part and the triboelectric part are 10.95 and 2.04 mW/cm(3),
      respectively. Moreover, influence of the triboelectric charges on the
      piezoelectric output voltage is investigated. Both finite element method
      simulations and experimental measurements are conducted to verify this
      phenomenon. The novel hybrid NG is also demonstrated as a power source for
      consumer electronics. Through one cycle of electric generation, 10 light-emitting
      diodes are lighted up instantaneously, and a 4-bit liquid crystal display can
      display continuously for more than 15 s. Besides, the device is integrated into a
      keyboard to harvest energy in the typing process. 

PMID- 24032721
TI  - Nine things to remember about human genome diversity.
AB  - Understanding how and why humans are biologically different is indispensable to
      get oriented in the ever-growing body of genomic data. Here we discuss the
      evidence based on which we can confidently state that humans are the least
      genetically variable primate, both when individuals and when populations are
      compared, and that each individual genome can be regarded as a mosaic of
      fragments of different origins. Each population is somewhat different from any
      other population, and there are geographical patterns in that variation. These
      patterns clearly indicate an African origin for our species, and keep a record of
      the main demographic changes accompanying the peopling of the whole planet.
      However, only a minimal fraction of alleles, and a small fraction of combinations
      of alleles along the chromosome, is restricted to a single geographical region
      (and even less so to a single population), and diversity between members of the
      same population is very large. The small genomic differences between populations
      and the extensive allele sharing across continents explain why historical
      attempts to identify, once and for good, major biological groups in humans have
      always failed. Nevertheless, racial categorization is all but gone, especially in
      clinical studies. We argue that racial labels may not only obscure important
      differences between patients but also that they have become positively useless
      now that cheap and reliable methods for genotyping are making it possible to
      pursue the development of truly personalized medicine. 

PMID- 24032722
TI  - Association of CXCL12 and CXCR4 gene polymorphisms with the susceptibility and
      prognosis of renal cell carcinoma.
AB  - CXCL12 and its unique receptor CXCR4, play important roles in inflammation and
      cancer metastasis. This study was undertaken to investigate the association of
      CXCL12 and CXCR4 polymorphisms with risk and prognosis of renal cell carcinoma
      (RCC) in the Chinese population. Blood was collected from 322 RCC patients and
      402 healthy controls. The CXCL12 rs1801157G/A polymorphism and CXCR4 rs2228014C/T
      polymorphism were genotyped by polymerase chain reaction-restriction fragment
      length polymorphism. Results showed that prevalence of CXCL12 rs1801157AA
      genotype was significantly increased in RCC cases than in controls [odds ratio
      (OR) = 3.07, 95% confidence interval (CI), 1.98-5.46, P = 6.1 * 10(-6) ; data
      were adjusted for age and sex]. Similarly, subjects carrying CXCR4 rs2228014CT or
      TT genotypes showed significantly high risk of RCC (OR = 1.77, 95% CI, 1.28-2.71,
      P = 0.0003; OR = 4.01, 95% CI, 1.87-9.12, P = 7.8 * 10(-4) , respectively; data
      were adjusted for age and sex). When analyzing the survival time of RCC, patients
      with CXCL12 rs1801157AA genotype revealed significantly shorter survival time
      compared to cases with CXCL12 rs1801157GG and GA genotypes (P = 0.001), whereas
      RCC patients carrying CXCR4 rs2228014CT and TT genotypes showed shorter survival
      time than the wild type (P = 0.002). These data indicated that CXCL12 and CXCR4
      may be new risk factors for RCC and could be used as prognostic markers for this
      malignancy. 

PMID- 24032723
TI  - Interleukin-6 level and gene polymorphism in spontaneous miscarriage.
AB  - The aetiology of spontaneous miscarriage, the most common pregnancy complication,
      remains undefined. One of postulated factors involved in miscarriage pathology is
      interleukin 6 (IL-6). Therefore, the aim of the study was to evaluate IL-6 and
      interleukin 6 receptor (IL-6R) gene polymorphisms in patients with spontaneous
      miscarriage. One hundred fifty-seven patients diagnosed with spontaneous
      miscarriage and age and gestational time matched controls were included in the
      case-control study. In all study participants circulating IL-6 levels
      (chemiluminescent immunoassay) and IL6-174G>C as well as IL6R rs2228145:A>C
      polymorphisms were evaluated. The distribution of IL6 as well as IL6R alleles and
      genotypes were similar in the controls and patients with miscarriage. Only a
      trend of more frequent appearance of -174GC+CC and C allele in the patients with
      miscarriage was noted. Blood serum concentrations of IL-6 were significantly
      elevated in patients with miscarriage vs those with physiological pregnancy.
      Likewise, IL-6 concentrations differ significantly with the types of miscarriage.
      The highest concentrations of the cytokine was seen in subjects with incomplete
      miscarriage (4.28 +/- 4.88 pg/ml) followed by imminent miscarriage (2.97 +/- 2.42
      pg/ml), and then missed miscarriage (2.07 +/- 1.90 pg/ml), being significantly
      the lowest in missed miscarriage group. No association between the IL6 genotype
      and IL-6 serum concentration were noted, both in the miscarriage group and in the
      control group. The findings of the study support the role of IL-6 in spontaneous
      miscarriage irrespectively of its type. However, no correlation between
      circulating IL-6 and IL6 gene polymorphism, as well as IL-6 and IL-6R
      polymorphisms associations with spontaneous miscarriage were revealed. 

PMID- 24032724
TI  - Distribution patterns of variability for 18 immune system genes in Amerindians-
      relationship with history and epidemiology.
AB  - Native American populations generally have a higher prevalence of infectious
      diseases than non-Native populations and this fact can induce different pressures
      in their immune system. We investigated the patterns of population
      differentiation (FST ) of 32 polymorphisms related to adaptive immune response in
      four Native American populations (Ache, Guarani-Kaiowa, Guarani-Nandeva and
      Kaingang), and the results were compared with the three major world population
      data [Yoruba of Ibadan, Nigeria (YRI), Utah residents with northern and Western
      Europe ancestry (CEU) and Han Chinese of Beijing, China (CHB)] available in the
      HapMap database. The Ache clearly differentiated from the other Amerindians, but
      when all Native Americans were compared with the samples of other ethnic groups
      the lowest difference (0.08) was found with CHB (Asians), the second lowest
      (0.15) with YRI (Africans) and the most marked with CEU (European-derived). The
      considerable intra and interethnic differences found can be explained both in
      terms of diverse evolutionary distances and more recent environmental pathogen
      exposures; and they should be appropriately considered prior to any specific
      public health action. 

PMID- 24032725
TI  - Annexin A11 gene polymorphism (R230C variant) and sarcoidosis in a Portuguese
      population.
AB  - A recent genome-wide association study detected a protective effect for the
      annexin A11 rs1049550*T allele (R230Cvariant) in susceptibility to sarcoidosis.
      We evaluated the association between rs1049550 C/T and sarcoidosis
      susceptibility, distinct disease phenotypes and evolution in a Portuguese
      population. We performed a case-control study of 208 patients and 197 healthy
      controls. Samples were genotyped for rs1049550 C/T using real-time polymerase
      chain reaction. The frequency of the annexin A11 rs1049550*T allele was
      significantly lower in patients than in controls (33.2 vs 44.9%, P < 0.001). Odds
      ratio of 0.52 and 0.44 were obtained, respectively for carriers of one (CT) and
      two (TT) copies normalized to the CC wild-type genotype (P < 0.001). There were
      no significant differences in patients with and without Lofgren syndrome. A
      significant increase in the frequency of the T allele was observed in patients
      with bronchoalveolar lavage (BAL) fluid neutrophilia (P = 0.04). No significant
      associations were seen for lung function pattern, radiological stages or
      different forms of disease evolution. Our study confirms that rs1049550*T allele
      exerts a significant protective effect on sarcoidosis susceptibility. Given the
      role of annexin A11 in cell division, apoptosis and neutrophil function, this
      polymorphism may affect key elements of granulomatous and interstitial
      inflammation in sarcoidosis. 

PMID- 24032726
TI  - A novel HLA allele, HLA-A*02:393, identified in a two generation Italian family.
AB  - HLA-A*02:393 differs by a single nucleotide substitution from both A*02:26
      (A524G) and from A*02:40:01 (T527A). 

PMID- 24032727
TI  - A novel HLA-B allele, HLA-B*39:01:16, identified by super high-resolution single
      molecule sequence-based typing in a Japanese individual.
AB  - HLA-B*39:01:16 differs from B*39:01:03 by one nucleotide 348 (codon 116) T to C. 

PMID- 24032728
TI  - Identification of a novel HLA-B*40 allele, HLA-B*40:211, in a Chinese individual.
AB  - HLA-B*40:211 allele differs from HLA-B*40:02:01 by an amino acid exchange at
      position 132, which has a missense mutation in exon 3 from Ser to Tyr. 

PMID- 24032729
TI  - A novel HLA allele, HLA-B*40:227, was identified by polymerase chain reaction
      sequence-based typing in a Chinese individual.
AB  - HLA-B*40:227 has one nucleotide change from B*40:01:01 in exon 2 at position 265
      C>G. 

PMID- 24032730
TI  - The novel HLA-B*48:19 allele, identified by sequence-based typing in a Chinese
      individual.
AB  - HLA-B*48:19 differs from HLA-B*48:01:01 exon 3 2 nt at position 195 and 196 (C->T
      and T->G). 

PMID- 24032731
TI  - Identification of a novel HLA-DRB1*13 variant allele: DRB1*13:154.
AB  - A newly identified allele, named HLA-DRB1*13:154, differs from DRB1*13:13 by the
      single nucleotide substitution 227T-A at codon 47 in exon 2. 

PMID- 24032732
TI  - A new HLA-DPB1 allele, HLA-DPB1*142:01, identified in a Peruvian organ donor.
AB  - The new HLA-DPB1*142:01 allele differs from DPB1*26:01:02 and DPB1*56:01 at
      codons 65 (I65>L65) and 35 (F35>Y35), respectively. 

PMID- 24032733
TI  - Identification of a new HLA-DQB1*03 variant, DQB1*03:39, by sequence-based typing
      in a Chinese Han individual.
AB  - HLA-DQB1*03:39 is identical to HLA-DQB1*03:03:02, except for one nucleotide
      change at nt 477 (C->G) in exon 3. 

PMID- 24032734
TI  - A new allele, HLA-DQB1*04:09.
AB  - The novel allele HLA-DQB1*04:09 differs from DQB1*04:02:01 by three nonsynonymous
      nucleotide substitutions in exon 2. 

PMID- 24032735
TI  - A nonsynonymous mutation at HLA-E defines the new E*01:06 allele in Brazilian
      individuals.
AB  - We report a novel nonclassical class I HLA-E*01:06 allele observed in Brazilian
      individuals. 

PMID- 24032736
TI  - Identification of a novel allele MICA*008:05 by sequence-based typing.
AB  - The new allele differs from MICA*008:01:01 by a single nucleotide substitution at
      position 591 of exon 3. 

PMID- 24032737
TI  - Nomenclature for factors of the HLA system, update April 2013.

PMID- 24032738
TI  - Nomenclature for factors of the HLA system, update May 2013.

PMID- 24032739
TI  - Nomenclature for factors of the HLA system, update June 2013.

PMID- 24032740
TI  - A histochemical study of the posterior silk glands of Bombyx mori during
      metamorphosis from larvae to pupae using frozen sections.
AB  - The fine structures of the whole bodies and the posterior silk glands of Bombyx
      mori during metamorphosis from larvae to pupae in the cocoon were preserved
      virtually without damage when frozen sections were prepared using an adhesive
      plastic film. We used frozen sections for histochemical and enzyme histochemistry
      to characterize the metamorphosis of the posterior silk glands. Frozen sections
      were stained with DAPI to observe nuclear changes, examined using the TUNEL
      method to detect DNA fragments, and investigated using in situ hybridization to
      detect B. mori caspase expression. Both DNA fragments and expression of B. mori
      caspase increased with progressing metamorphosis. The degeneration of the
      posterior silk gland during metamorphosis appears to be an apoptotic event.

PMID- 24032741
TI  - A randomized controlled trial of third-trimester routine ultrasound in a non
      selected population.
AB  - OBJECTIVE: To compare detection rates of small-for-gestational-age fetuses, large
      for-gestational-age fetuses, congenital anomalies and adverse perinatal outcomes
      in pregnancies randomized to third-trimester routine ultrasound or ultrasound on
      clinical indication. DESIGN: Randomized controlled trial. SETTING: National
      Center for Fetal Medicine in Norway between 1989 and 1992. POPULATION: A total of
      6780 pregnancies from a non-selected population. METHODS: Two routine ultrasound
      examinations at 18 and 33 weeks were compared with routine ultrasound at 18 weeks
      and ultrasound on clinical indication. Suspected small-for-gestational-age
      fetuses were followed with serial scans and cardiotocography. Doppler ultrasound
      was not used. MAIN OUTCOME MEASURES: Detection rates of small-for-gestational-age
      and large-for-gestational-age fetuses, congenital anomalies and adverse perinatal
      outcomes. RESULTS: Third trimester routine ultrasound improved detection rates of
      small-for-gestational-age fetuses from 46 to 80%, but overall perinatal morbidity
      and mortality remained unchanged. Detection of large-for-gestational-age fetuses
      increased from 36 to 91%. There was a significant increase of induction of labor
      and elective cesarean sections due to suspected small-for-gestational-age and a
      significant decrease of induction of labor and elective cesarean sections due to
      suspected large-for-gestational-age in the study group; there were no other
      differences regarding intervention. The detection rate of congenital anomalies
      was 56%, with no significant difference between the groups. CONCLUSIONS: Routine
      use of third-trimester routine ultrasound increased detection rates of small-for
      gestational-age and large-for-gestational-age fetuses. This did not alter
      perinatal outcomes. Third-trimester ultrasound screening should not be rejected
      before a policy of adding Doppler surveillance to the high-risk group identified
      has been investigated further.

PMID- 24032743
TI  - Fractalkine/CX3CL1 modulates GABAA currents in human temporal lobe epilepsy.
AB  - PURPOSE: The chemokine fractalkine/CX3CL1 and its receptor CX3CR1 are widely
      expressed in the central nervous system (CNS). Recent evidence showed that CX3CL1
      participates in inflammatory responses that are common features of CNS disorders,
      such as epilepsy. Mesial temporal lobe epilepsy (MTLE) is the prevalent form of
      focal epilepsy in adults, and hippocampal sclerosis (HS) represents the most
      common underlying pathologic abnormality, as demonstrated at autopsy and
      postresection studies. Relevant features of MTLE are a characteristic pattern of
      neuronal loss, as are astrogliosis and microglia activation. Several factors
      affect epileptogenesis in patients with MTLE, including a lack of gamma
      aminobutyric acid (GABA)ergic inhibitory efficacy. Therefore, experiments were
      designed to investigate whether, in MTLE brain tissues, CX3CL1 may influence
      GABAA receptor (GABAA R) mediated transmission, with a particular focus on the
      action of CX3CL1 on the use-dependent decrease (rundown) of the GABA-evoked
      currents (IGABA ), a feature underlying the reduction of GABAergic function in
      epileptic tissue. METHODS: Patch-clamp recordings were obtained from cortical
      pyramidal neurons in slices from six MTLE patients after surgery. Alternatively,
      the cell membranes from epileptic brain tissues of 17 MTLE patients or from
      surgical samples and autopsies of nonepileptic patients were microtransplanted
      into Xenopus oocytes, and IGABA were recorded using the standard two
      microelectrode voltage-clamp technique. Immunohistochemical staining and double
      labeling studies were carried out on the same brain tissues to analyze CX3CR1
      expression. KEY FINDINGS: In native pyramidal neurons from cortical slices of
      patients with MTLE, CX3CL1 reduced IGABA rundown and affected the recovery of
      IGABA amplitude from rundown. These same effects were confirmed in oocytes
      injected with cortical and hippocampal MTLE membranes, whereas CX3CL1 did not
      influence IGABA in oocytes injected with nonepileptic tissues. Consistent with a
      specific effect of CX3CL1 on tissues from patients with MTLE, CX3CR1
      immunoreactivity was higher in MTLE sclerotic hippocampi than in control tissues,
      with a prominent expression in activated microglial cells. SIGNIFICANCE: These
      findings indicate a role for CX3CL1 in MTLE, supporting recent evidence on the
      relevance of brain inflammation in human epilepsies. Our data demonstrate that in
      MTLE tissues the reduced GABAergic function can be modulated by CX3CL1. The
      increased CX3CR1 expression in microglia and the modulation by CX3CL1 of
      GABAergic currents in human epileptic brain suggests new therapeutic approaches
      for drug-resistant epilepsies based on the evidence that the propagation of
      seizures can be influenced by inflammatory processes.

PMID- 24032745
TI  - Another case of concomitant fetal renal tubular dysgenesis and placental massive
      perivillous fibrin deposition.

PMID- 24032744
TI  - Targeting the ABCG2-overexpressing multidrug resistant (MDR) cancer cells by
      PPARgamma agonists.
AB  - BACKGROUND AND PURPOSE: Multidrug resistance (MDR), usually mediated by
      overexpression of efflux transporters such as P-gp, ABCG2 and/or MRP1, remains a
      major obstacle hindering successful cancer chemotherapy. There has been great
      interest in the development of inhibitors towards these transporters to
      circumvent resistance. However, since the inhibition of transporter is not
      specific to cancer cells, a decrease in the cytotoxic drug dosing may be needed
      to prevent excess toxicity, thus undermining the potential benefit brought about
      by a drug efflux inhibitor. The design of potent MDR modulators specific towards
      resistant cancer cells and devoid of drug-drug interactions will be needed to
      effect MDR reversal. EXPERIMENTAL APPROACH: Recent evidence suggests that the
      PTEN/PI3K/Akt pathway may be exploited to alter ABCG2 subcellular localization,
      thereby circumventing MDR. Three PPARgamma agonists (telmisartan, pioglitazone
      and rosiglitazone) that have been used in the clinics were tested for their
      effect on the PTEN/PI3K/Akt pathway and possible reversal of ABCG2-mediated drug
      resistance. KEY RESULTS: The PPARgamma agonists were found to be weak ABCG2
      inhibitors by drug efflux assay. They were also shown to elevate the reduced PTEN
      expression in a resistant and ABCG2-overexpressing cell model, which inhibit the
      PI3K-Akt pathway and lead to the relocalization of ABCG2 from the plasma membrane
      to the cytoplasma, thus apparently circumventing the ABCG2-mediated MDR.
      CONCLUSIONS AND IMPLICATIONS: Since this PPARgamma/PTEN/PI3K/Akt pathway
      regulating ABCG2 is only functional in drug-resistant cancer cells with PTEN
      loss, the PPARgamma agonists identified may represent promising agents targeting
      resistant cells for MDR reversal.

PMID- 24032746
TI  - High efficiency hybrid silicon nanopillar-polymer solar cells.
AB  - Recently, inorganic/organic hybrid solar cells have been considered as a viable
      alternative for low-cost photovoltaic devices because the Schottky junction
      between inorganic and organic materials can be formed employing low temperature
      processing methods. We present an efficient hybrid solar cell based on highly
      ordered silicon nanopillars (SiNPs) and poly(3,4-ethylene
      dioxythiophene):polystyrenesulfonate (PEDOT:PSS). The proposed device is formed
      by spin coating the organic polymer PEDOT:PSS on a SiNP array fabricated using
      metal assisted electroless chemical etching process. The characteristics of the
      hybrid solar cells are investigated as a function of SiNP height. A maximum power
      conversion efficiency (PCE) of 9.65% has been achieved for an optimized SiNP
      array hybrid solar cell with nanopillar height of 400 nm, despite the absence of
      a back surface field enhancement. The effect of an ultrathin atomic layer
      deposition (ALD), grown aluminum oxide (Al2O3), as a passivation layer
      (recombination barrier) has also been studied for the enhanced electrical
      performance of the device. With the inclusion of the ultrathin ALD deposited
      Al2O3 between the SiNP array textured surface and the PEDOT:PSS layer, the PCE of
      the fabricated device was observed to increase to 10.56%, which is ~10% greater
      than the corresponding device without the Al2O3 layer. The device described
      herein is considered to be promising toward the realization of a low-cost, high
      efficiency inorganic/organic hybrid solar cell. 

PMID- 24032748
TI  - Methylprednisolone fails to attenuate lung injury in a mouse model of transfusion
      related acute lung injury.
AB  - BACKGROUND: Transfusion-related acute lung injury (TRALI) is the leading cause of
      transfusion-related morbidity and mortality. Anecdotally, TRALI patients have
      been treated with corticosteroids. However, evidence for its therapeutic
      rationale in TRALI is lacking. We determined the effects of corticosteroids on
      lung injury in a "two-hit" mouse model of antibody-mediated TRALI. STUDY DESIGN
      AND METHODS: BALB/c mice were primed with lipopolysaccharide, after which TRALI
      was induced by injecting major histocompatibility complex (MHC)-I antibody
      against H2K(d) . Mice infused with phosphate-buffered saline served as controls.
      Simultaneously, one group of TRALI mice was infused with methylprednisolone (MPS;
      2 mg/kg). Mice were supported by mechanical ventilation for 2 hours, after which
      bronchoalveolar lavage fluid (BALF) and lung homogenate were obtained. Statistics
      were obtained by one-way analysis of variance or Kruskal-Wallis. RESULTS:
      Injection of MHC-I antibodies resulted in TRALI, indicated by pulmonary edema and
      increased BALF levels of protein and the proinflammatory mediators macrophage
      inflammatory protein-2, keratinocyte-derived chemokine, and interleukin (IL)-6.
      Administration of MPS did not affect the amount of edema nor pulmonary protein
      and chemokine levels. MPS reduced systemic inflammatory reaction as well as IL-6
      levels in the BALF. CONCLUSION: In a two-hit model of antibody-mediated TRALI,
      MPS attenuated the IL-6 host response, but failed to prevent the development of
      lung injury.

PMID- 24032747
TI  - Arabidopsis thaliana Nfu2 accommodates [2Fe-2S] or [4Fe-4S] clusters and is
      competent for in vitro maturation of chloroplast [2Fe-2S] and [4Fe-4S] cluster
      containing proteins.
AB  - Nfu-type proteins are essential in the biogenesis of iron-sulfur (Fe-S) clusters
      in numerous organisms. A number of phenotypes including low levels of Fe-S
      cluster incorporation are associated with the deletion of the gene encoding a
      chloroplast-specific Nfu-type protein, Nfu2 from Arabidopsis thaliana (AtNfu2).
      Here, we report that recombinant AtNfu2 is able to assemble both [2Fe-2S] and
      [4Fe-4S] clusters. Analytical data and gel filtration studies support
      cluster/protein stoichiometries of one [2Fe-2S] cluster/homotetramer and one [4Fe
      4S] cluster/homodimer. The combination of UV-visible absorption and circular
      dichroism and resonance Raman and Mossbauer spectroscopies has been employed to
      investigate the nature, properties, and transfer of the clusters assembled on
      Nfu2. The results are consistent with subunit-bridging [2Fe-2S](2+) and [4Fe
      4S](2+) clusters coordinated by the cysteines in the conserved CXXC motif. The
      results also provided insight into the specificity of Nfu2 for the maturation of
      chloroplastic Fe-S proteins via intact, rapid, and quantitative cluster transfer.
      [2Fe-2S] cluster-bound Nfu2 is shown to be an effective [2Fe-2S](2+) cluster
      donor for glutaredoxin S16 but not glutaredoxin S14. Moreover, [4Fe-4S] cluster
      bound Nfu2 is shown to be a very rapid and efficient [4Fe-4S](2+) cluster donor
      for adenosine 5'-phosphosulfate reductase (APR1), and yeast two-hybrid studies
      indicate that APR1 forms a complex with Nfu2 but not with Nfu1 and Nfu3, the two
      other chloroplastic Nfu proteins. This cluster transfer is likely to be
      physiologically relevant and is particularly significant for plant metabolism as
      APR1 catalyzes the second step in reductive sulfur assimilation, which ultimately
      results in the biosynthesis of cysteine, methionine, glutathione, and Fe-S
      clusters.

PMID- 24032750
TI  - Genetic programming and serial processing for time series classification.
AB  - This work describes an approach devised by the authors for time series
      classification. In our approach genetic programming is used in combination with a
      serial processing of data, where the last output is the result of the
      classification. The use of genetic programming for classification, although still
      a field where more research in needed, is not new. However, the application of
      genetic programming to classification tasks is normally done by considering the
      input data as a feature vector. That is, to the best of our knowledge, there are
      not examples in the genetic programming literature of approaches where the time
      series data are processed serially and the last output is considered as the
      classification result. The serial processing approach presented here fills a gap
      in the existing literature. This approach was tested in three different problems.
      Two of them are real world problems whose data were gathered for online or
      conference competitions. As there are published results of these two problems
      this gives us the chance to compare the performance of our approach against top
      performing methods. The serial processing of data in combination with genetic
      programming obtained competitive results in both competitions, showing its
      potential for solving time series classification problems. The main advantage of
      our serial processing approach is that it can easily handle very large datasets. 

PMID- 24032749
TI  - Identification of co-expressed gene signatures in mouse B1, marginal zone and B2
      B-cell populations.
AB  - In mice, three major B-cell subsets have been identified with distinct
      functionalities: B1 B cells, marginal zone B cells and follicular B2 B cells.
      Here, we used the growing body of publicly available transcriptomics data to
      create an expression atlas of 84 gene expression microarray data sets of distinct
      mouse B-cell subsets. These data were subjected to network-based cluster analysis
      using BioLayout Express(3D). Using this analysis tool, genes with related
      functions clustered together in discrete regions of the network graph and enabled
      the identification of transcriptional networks that underpinned the functional
      activity of distinct cell populations. Some gene clusters were expressed highly
      by most of the cell populations included in this analysis (such as those with
      activity related to house-keeping functions). Others contained genes with
      expression patterns specific to distinct B-cell subsets. While these clusters
      contained many genes typically associated with the activity of the cells they
      were specifically expressed in, many novel B-cell-subset-specific candidate genes
      were identified. A large number of uncharacterized genes were also represented in
      these B-cell lineage-specific clusters. Further analysis of the activities of
      these uncharacterized candidate genes will lead to the identification of novel B
      cell lineage-specific transcription factors and regulators of B-cell function. We
      also analysed 36 microarray data sets from distinct human B-cell populations.
      These data showed that mouse and human germinal centre B cells shared similar
      transcriptional features, whereas mouse B1 B cells were distinct from proposed
      human B1 B cells.

PMID- 24032751
TI  - Effect of pore structure of nanometer scale porous films on the measured elastic
      modulus.
AB  - The impact of pore structure of nanoporous films on the measured elastic modulus
      is demonstrated for silica-based nanoporous low-k films that are fabricated using
      an alternative manufacturing sequence which allows a separate control of porosity
      and matrix properties. For this purpose, different experimental techniques for
      measuring the elastic properties were compared, including nanoindentation, laser
      induced surface acoustic wave spectroscopy (LAwave), and ellipsometric
      porosimetry (EP). The link between the elastic response of these nanoporous
      materials and their internal pore structure was investigated using positronium
      annihilation lifetime spectroscopy (PALS), EP, and diffusion experiments. It is
      shown that the absolute value of the Berkovich indentation modulus is very
      sensitive to the local pore structure and stiffness of the substrate and can be
      influenced by densification and/or anisotropic elasticity upon indentation, while
      on the other hand spherical indentation results are less sensitive to the local
      pore structure. The comparison of Berkovich and spherical indentation results
      combined with finite element simulations can potentially reveal changes in the
      internal structure of the film. For nanoporous films with porosity above the
      percolation threshold, the elastic modulus results obtained with LAwave and EP
      agree very well with spherical indentation results. On the other hand, below the
      percolation threshold, the elastic modulus values determined by these techniques
      deviate from the spherical indentation results. This was explained in terms of
      specific technique related effects that appear to be sensitive to the specific
      arrangement and morphology of the pores. 

PMID- 24032754
TI  - Good grief.

PMID- 24032752
TI  - Spherical monovalent ions at aqueous liquid-vapor interfaces: interfacial
      stability and induced interface fluctuations.
AB  - Ion-specific interfacial behaviors of monovalent halides impact processes such as
      protein denaturation, interfacial stability, and surface tension modulation, and
      as such, their molecular and thermodynamic underpinnings garner much attention.
      We use molecular dynamics simulations of monovalent anions in water to explore
      effects on distant interfaces. We observe long-ranged ion-induced perturbations
      of the aqueous environment, as suggested by experiment and theory. Surface stable
      ions, characterized as such by minima in potentials of mean force computed using
      umbrella sampling MD simulations, induce larger interfacial fluctuations compared
      to nonsurface active species, conferring more entropy approaching the interface.
      Smaller anions and cations show no interfacial potential of mean force minima.
      The difference is traced to hydration shell properties of the anions, and the
      coupling of these shells with distant solvent. The effects correlate with the
      positions of the anions in the Hofmeister series (acknowledging variations in
      force field ability to recapitulate essential underlying physics), suggesting how
      differences in induced, nonlocal perturbations of interfaces may be related to
      different specific-ion effects in dilute biophysical and nanomaterial systems. 

PMID- 24032753
TI  - Prevalence and correlates of pain and pain treatment in a western Kenya referral
      hospital.
AB  - BACKGROUND: Pain is often inadequately evaluated and treated in sub-Saharan
      Africa (SSA). OBJECTIVE: We sought to assess pain levels and pain treatment in
      400 hospitalized patients at a national referral hospital in western Kenya, and
      to identify factors associated with pain and pain treatment. DESIGN: Using face
      validated Kiswahili versions of two single-item pain assessment tools, the
      Numerical Rating Scale (NRS) and the Faces Pain Scale-Revised (FPS-R), we
      determined patients' pain levels. Additional data collected included patient
      demographics, prescribed analgesics, and administered analgesics. We calculated
      mean pain ratings and pain management index (PMI) scores. RESULTS: Averaged
      between the NRS and FPS-R, 80.5% of patients endorsed a nonzero level of pain and
      30% of patients reported moderate to severe pain. Older patients, patients with
      HIV, and cancer patients had higher pain ratings. Sixty-six percent of patients
      had been prescribed analgesics at some point during their hospitalization, the
      majority of which were nonopioids. A majority of patients (66%) had undertreated
      pain (negative scores on the PMI). CONCLUSION: This study shows that hospitalized
      patients in Kenya are experiencing pain and that this pain is often undertreated.

PMID- 24032755
TI  - Effectiveness of integration of palliative medicine specialist services into the
      intensive care unit of a community teaching hospital.
AB  - BACKGROUND: Collaboration between palliative medicine and the intensive care unit
      (ICU) represents best practice and offers important benefits. However, achieving
      effective collaboration between these two specialties can be challenging.
      OBJECTIVE: Assess effectiveness of integrating palliative medicine specialists in
      the ICU. DESIGN: Retrospective chart review. RESULTS: Of 201 patients who
      qualified for palliative consultation using a palliative screening tool, 92 were
      referred and 109 were not referred for palliative medicine consultation. The
      number of screening criteria met was similar between the two groups. Palliative
      medicine consult volume increased significantly compared with preintegration
      (7.7+/-3.4 versus 4.4+/-2.8 consults per month, p=0.04). No significant
      difference in hospital mortality was found between the referred and unreferred
      groups (32/92 [35%] versus 26/109 [24%], p=0.09). ICU length of stay was
      significantly shorter in the referred group (7 versus 11 days, p<0.001). Referred
      patients were more frequently enrolled in hospice compared with unreferred
      patients (32/92 [37%] versus 3/109 [3%], p<0.001). ICU physicians referred
      patients significantly more often for dementia and ventilator withdrawal (13/16,
      p=0.003; 24/29, p<0.001, respectively) and significantly less often for ICU stay
      longer than 10 days (21 versus 49, p=0.001). CONCLUSIONS: Integrating palliative
      medicine specialists into intensive care was associated with a significant
      increase in use of palliative medicine services and a significant decrease in ICU
      length of stay for referred patients without a significant increase in mortality.
      The screening tool effectively identified patients at high risk of death. Given
      the high mortality rate of the unreferred patients, the criteria could be more
      widely adopted by ICU physicians to consider expanding palliative medicine
      referrals.

PMID- 24032756
TI  - Chronic cutaneous cytomegalovirus infection in a patient with severe combined
      immunodeficiency syndrome.

PMID- 24032757
TI  - Catalytic asymmetric insertion of diazoesters into aryl-CHO bonds: highly
      enantioselective construction of chiral all-carbon quaternary centers.
AB  - This paper describes a catalytic enantioselective route to synthesize
      functionalized all-carbon quaternary acyclic systems via a boron Lewis acid
      promoted formal C-C insertion of diazoesters into aryl-CHO bonds. In the presence
      of chiral (S)-oxazaborolidinium cation 1d as a catalyst, the reaction proceeded
      in good yield (up to 83%) with good regioselectivity (up to 88:12) and excellent
      enantioselectivity (up to 99% ee). The synthetic potential of this method was
      illustrated by conversion of the products to both alpha- and beta-amino esters. 

PMID- 24032758
TI  - Development of enantioselective synthetic routes to the hasubanan and acutumine
      alkaloids.
AB  - We describe a general strategy to prepare the hasubanan and acutumine alkaloids,
      a large family of botanical natural products that display antitumor, antiviral,
      and memory-enhancing effects. The absolute stereochemistry of the targets is
      established by an enantioselective Diels-Alder reaction between 5
      (trimethylsilyl)cyclopentadiene (36) and 5-(2-azidoethyl)-2,3
      dimethoxybenzoquinone (24). The Diels-Alder adduct 38 is transformed to the
      tetracyclic imine 39 by a Staudinger reduction-aza-Wittig sequence. The latter
      serves as a universal precursor to the targets. Key carbon-carbon bond
      constructions include highly diastereoselective acetylide additions to the N
      methyliminium ion derived from 39 and Friedel-Crafts and Hosomi-Sakurai
      cyclizations to construct the carbocyclic skeleton of the targets. Initially,
      this strategy was applied to the syntheses of (-)-acutumine (4), (-)
      dechloroacutumine (5), and four hasubanan alkaloids (1, 2, 3, and 8). Herein, the
      synthetic route is adapted to the syntheses of six additional hasubanan alkaloids
      (12, 13, 14, 15, 18, and 19). The strategic advantage of 5
      (trimethylsilyl)cyclopentadiene Diels-Alder adducts is demonstrated by site
      selective functionalization of distal carbon-carbon pi-bonds in the presence of
      an otherwise reactive norbornene substructure. Evaluation of the
      antiproliferative properties of the synthetic metabolites revealed that four
      hasubanan alkaloids are submicromolar inhibitors of the N87 cell line. 

PMID- 24032761
TI  - Violation of detailed balance accelerates relaxation.
AB  - Recent studies have experienced the acceleration of convergence in Markov chain
      Monte Carlo methods implemented by the systems without detailed balance condition
      (DBC). However, such advantage of the violation of DBC has not been confirmed in
      general. We investigate the effect of the absence of DBC on the convergence
      toward equilibrium. Surprisingly, it is shown that the DBC violation always makes
      the relaxation faster. Our result implies the existence of a kind of
      thermodynamic inequality that connects the nonequilibrium process relaxing toward
      steady state with the relaxation process which has the same probability
      distribution as its equilibrium state. 

PMID- 24032760
TI  - IgG4-related disease with cutaneous manifestations treated with rituximab: case
      report and literature review.
AB  - Immunoglobulin type gamma 4 (Ig)G4-related disease (IgG4-RD) is a relatively
      recently described clinical entity characterised by elevated levels of serum IgG4
      and tissue infiltration of IgG4+ plasma cells in various organ systems. Cutaneous
      involvement is rare but is becoming increasingly appreciated; typically
      presenting as erythematous papules and/or nodules that are commonly pruritic. We
      report a case of IgG4-RD presenting with persistent pruritic papules and
      unilateral parotid swelling. His serum IgG4 level was elevated and a histological
      examination of his skin biopsies found a lymphoplasmacytic infiltration with an
      excess of IgG4+ non-clonal plasma cells. The patient was intolerant of oral
      prednisolone, however complete resolution of the cutaneous lesions was achieved
      with the anti-CD20 antibody, rituximab. 

PMID- 24032762
TI  - Spatially modulated kinks in shallow granular layers.
AB  - We report on the experimental observation of spatially modulated kinks in a
      shallow one-dimensional fluidized granular layer subjected to a periodic air
      flow. We show the appearance of these solutions as the layer undergoes a
      parametric instability. Due to the inherent fluctuations of the granular layer,
      the kink profile exhibits an effective wavelength, a precursor, which modulates
      spatially the homogeneous states and drastically modifies the kink dynamics. We
      characterize the average and fluctuating properties of this solution. Finally, we
      show that the temporal evolution of these kinks is dominated by a hopping
      dynamics, related directly to the underlying spatial structure. 

PMID- 24032759
TI  - Toxicity and efficacy evaluation of multiple targeted polymalic acid conjugates
      for triple-negative breast cancer treatment.
AB  - Engineered nanoparticles are widely used for delivery of drugs but frequently
      lack proof of safety for cancer patient's treatment. All-in-one covalent
      nanodrugs of the third generation have been synthesized based on a poly(beta-L
      malic acid) (PMLA) platform, targeting human triple-negative breast cancer
      (TNBC). They significantly inhibited tumor growth in nude mice by blocking
      synthesis of epidermal growth factor receptor, and alpha4 and beta1 chains of
      laminin-411, the tumor vascular wall protein and angiogenesis marker. PMLA and
      nanodrug biocompatibility and toxicity at low and high dosages were evaluated in
      vitro and in vivo. The dual-action nanodrug and single-action precursor
      nanoconjugates were assessed under in vitro conditions and in vivo with multiple
      treatment regimens (6 and 12 treatments). The monitoring of TNBC treatment in
      vivo with different drugs included blood hematologic and immunologic analysis
      after multiple intravenous administrations. The present study demonstrates that
      the dual-action nanoconjugate is highly effective in preclinical TNBC treatment
      without side effects, supported by hematologic and immunologic assays data. PMLA
      based nanodrugs of the PolycefinTM family passed multiple toxicity and efficacy
      tests in vitro and in vivo on preclinical level and may prove to be optimized and
      efficacious for the treatment of cancer patients in the future.

PMID- 24032763
TI  - Oscillatory athermal quasistatic deformation of a model glass.
AB  - We report computer simulations of oscillatory athermal quasistatic shear
      deformation of dense amorphous samples of a three-dimensional model glass former.
      A dynamical transition is observed as the amplitude of the deformation is varied:
      For large values of the amplitude the system exhibits diffusive behavior and loss
      of memory of the initial conditions, whereas localization is observed for small
      amplitudes. Our results suggest that the same kind of transition found in driven
      colloidal systems is present in the case of amorphous solids (e.g., metallic
      glasses). The onset of the transition is shown to be related to the onset of
      energy dissipation. Shear banding is observed for large system sizes, without,
      however, affecting qualitative aspects of the transition. 

PMID- 24032764
TI  - Holographic measurements of anisotropic three-dimensional diffusion of colloidal
      clusters.
AB  - We measure all nonzero elements of the three-dimensional diffusion tensor D for
      clusters of colloidal spheres to a precision of 1% or better using digital
      holographic microscopy. We study both dimers and triangular trimers of spheres,
      for which no analytical calculations of the diffusion tensor exist. We observe
      anisotropic rotational and translational diffusion arising from the asymmetries
      of the clusters. In the case of the three-particle triangular cluster, we also
      detect a small but statistically significant difference in the rotational
      diffusion about the two in-plane axes. We attribute this difference to weak
      breaking of threefold rotational symmetry due to a small amount of particle
      polydispersity. Our experimental measurements agree well with numerical
      calculations and show how diffusion constants can be measured under conditions
      relevant to colloidal self-assembly, where theoretical and even numerical
      prediction is difficult. 

PMID- 24032765
TI  - Rotation-induced grain growth and stagnation in phase-field crystal models.
AB  - We consider grain growth and stagnation in polycrystalline microstructures. From
      the phase-field crystal modeling of the coarsening dynamics, we identify a
      transition from a grain-growth stagnation upon deep quenching below the melting
      temperature T(m) to a continuous coarsening at shallower quenching near T(m). The
      grain evolution is mediated by local grain rotations. In the deep quenching
      regime, the grain assembly typically reaches a metastable state where the kinetic
      barrier for recrystallization across boundaries is too large and grain rotation
      with subsequent coalescence or boundary motion is infeasible. For quenching near
      T(m), we find that the grain growth depends on the average rate of grain
      rotation, and follows a power-law behavior with time, with a scaling exponent
      that depends on the quenching depth.

PMID- 24032766
TI  - Temporal decorrelations in compressible isotropic turbulence.
AB  - Temporal decorrelations in compressible isotropic turbulence are studied using
      the space-time correlation theory and direct numerical simulation. A swept-wave
      model is developed for dilatational components, while the classic random sweeping
      model is proposed for solenoidal components. The swept-wave model shows that the
      temporal decorrelations in dilatational fluctuations are dominated by two
      physical processes: random sweeping and wave propagation. These models are
      supported by the direct numerical simulation of compressible isotropic
      turbulence, in the sense that all curves of normalized time correlations for
      different wave numbers collapse into a single one using the normalized time
      separations. The swept-wave model is further extended to account for a constant
      mean velocity. 

PMID- 24032767
TI  - Modified reduced Ostrovsky equation: integrability and breaking.
AB  - The modified reduced Ostrovsky equation is a reduction of the modified Korteweg
      de Vries equation, in which the usual linear dispersive term with a third-order
      derivative is replaced by a linear nonlocal integral term, representing the
      effect of background rotation. Here we study the case when the cubic nonlinear
      term has the same polarity as the rotation term. This equation is integrable
      provided certain slope constraints are satisfied. We demonstrate, through
      theoretical analysis and numerical simulations, that when this constraint is not
      satisfied at the initial time, wave breaking inevitably occurs. 

PMID- 24032768
TI  - Monte Carlo algorithm for simulating the O(N) loop model on the square lattice.
AB  - An efficient algorithm is presented to simulate the O(N) loop model on the square
      lattice for arbitrary values of N>0. The scheme combines the worm algorithm with
      a new data structure to resolve both the problem of loop crossings and the
      necessity of counting the number of loops at each Monte Carlo update. With the
      use of this scheme, the line of critical points (and other properties) of the
      O(N) model on the square lattice for 0<N<=2 have been determined. 

PMID- 24032769
TI  - Search times with arbitrary detection constraints.
AB  - Random encounters in space are central to describing diffusion-limited reactions,
      animal foraging, search processes, and many other situations in nature. These
      encounters, however, are often constrained by the capacity of the searcher to
      detect and/or recognize its target. This can be due to limited binding and
      perception abilities of the searcher or hiding and avoiding mechanisms used by
      the target. Hence detection failure upon passage over the target location turns
      the process into an n-passage problem, with n being random. Here we provide a
      general description of this detection problem for arbitrary dimensions and
      arbitrary detection constraints. The mean detection time (MDT) for a random
      searcher embedded in a sea of homogeneously distributed targets is obtained as a
      function of the target density rho, the size domain L, and the effective
      detection distance a. While the scaling with rho and L is found to be universal
      and equivalent to that found for the corresponding first-passage problem, the
      scaling of the MDT on a depends on the specific detection mechanism considered. 

PMID- 24032770
TI  - Ginzburg criterion for ionic fluids: the effect of Coulomb interactions.
AB  - The effect of the Coulomb interactions on the crossover between mean-field and
      Ising critical behavior in ionic fluids is studied using the Ginzburg criterion.
      We consider the charge-asymmetric primitive model supplemented by short-range
      attractive interactions in the vicinity of the gas-liquid critical point. The
      model without Coulomb interactions exhibiting typical Ising critical behavior is
      used to calibrate the Ginzburg temperature of the systems comprising
      electrostatic interactions. Using the collective variables method, we derive a
      microscopic-based effective Hamiltonian for the full model. We obtain explicit
      expressions for all the relevant Hamiltonian coefficients within the framework of
      the same approximation, i.e., the one-loop approximation. Then we consistently
      calculate the reduced Ginzburg temperature t(G) for both the purely Coulombic
      model (a restricted primitive model) and the purely nonionic model (a hard-sphere
      square-well model) as well as for the model parameters ranging between these two
      limiting cases. Contrary to the previous theoretical estimates, we obtain the
      reduced Ginzburg temperature for the purely Coulombic model to be about 20 times
      smaller than for the nonionic model. For the full model including both short
      range and long-range interactions, we show that t(G) approaches the value found
      for the purely Coulombic model when the strength of the Coulomb interactions
      becomes sufficiently large. Our results suggest a key role of Coulomb
      interactions in the crossover behavior observed experimentally in ionic fluids as
      well as confirm the Ising-like criticality in the Coulomb-dominated ionic
      systems.

PMID- 24032771
TI  - Local time in diffusive media and applications to imaging.
AB  - Local time is the measure of how much time a random walk has visited a given
      position. In multiple scattering media, where waves are diffuse, local time
      measures the sensitivity of the waves to the local medium's properties. Local
      variations of absorption, velocity, and scattering between two measurements yield
      variations in the wave field. These variations are proportional to the local time
      of the volume where the change happened and the amplitude of variation. The wave
      field variations are measured using correlations and can be used as input in a
      inversion algorithm to produce variation maps. The present article gives the
      expression of the local time in dimensions one, two, and three and an expression
      of its fluctuations, in order to perform such inversions and estimate their
      accuracy. 

PMID- 24032772
TI  - Solid-liquid transition in polydisperse Lennard-Jones systems.
AB  - We study melting of a face-centered crystalline solid consisting of polydisperse
      Lennard-Jones spheres with Gaussian polydispersity in size. The phase diagram
      reproduces the existence of a nearly temperature invariant terminal
      polydispersity (delta(t) =/~ 0.11), with no signature of reentrant melting. The
      absence of reentrant melting can be attributed to the influence of the attractive
      part of the potential upon melting. We find that at terminal polydispersity the
      fractional density change approaches zero, which seems to arise from vanishingly
      small compressibility of the disordered phase. At constant temperature and volume
      fraction the system undergoes a sharp transition from crystalline solid to the
      disordered amorphous or fluid state with increasing polydispersity. This has been
      quantified by second- and third-order rotational invariant bond orientational
      order, as well as by the average inherent structure energy. The translational
      order parameter also indicates a similar sharp structural change at delta =/~
      0.09 in case of T(*) = 1.0, phi = 0.58. The free energy calculation further
      supports the sharp nature of the transition. The third-order rotationally
      invariant bond order shows that with increasing polydispersity, the local cluster
      favors a more icosahedral arrangement and the system loses its local crystalline
      symmetry. Interestingly, the value of structure factor S(k) of the amorphous
      phase at delta =/~ 0.10 (just beyond the solid-liquid transition density at T(*)
      = 1) becomes 2.75, which is below the value of 2.85 required for freezing given
      by the empirical Hansen-Verlet rule of crystallization, well known in the theory
      of freezing.

PMID- 24032773
TI  - Dynamics of influence on hierarchical structures.
AB  - Dichotomous spin dynamics on a pyramidal hierarchical structure (the Bethe
      lattice) are studied. The system embodies a number of classes, where a class
      comprises nodes that are equidistant from the root (head node). Weighted links
      exist between nodes from the same and different classes. The spin (hereafter
      state) of the head node is fixed. We solve for the dynamics of the system for
      different boundary conditions. We find necessary conditions so that the classes
      eventually repudiate or acquiesce in the state imposed by the head node. The
      results indicate that to reach unanimity across the hierarchy, it suffices that
      the bottommost class adopts the same state as the head node. Then the rest of the
      hierarchy will inevitably comply. This also sheds light on the importance of mass
      media as a means of synchronization between the topmost and bottommost classes.
      Surprisingly, in the case of discord between the head node and the bottommost
      classes, the average state over all nodes inclines towards that of the bottommost
      class regardless of the link weights and intraclass configurations. Hence the
      role of the bottommost class is signified. 

PMID- 24032774
TI  - Avalanche dynamics of elastic interfaces.
AB  - Slowly driven elastic interfaces, such as domain walls in dirty magnets, contact
      lines wetting a nonhomogeneous substrate, or cracks in brittle disordered
      material proceed via intermittent motion, called avalanches. Here we develop a
      field-theoretic treatment to calculate, from first principles, the space-time
      statistics of instantaneous velocities within an avalanche. For elastic
      interfaces at (or above) their (internal) upper critical dimension d>=d(uc)
      (d(uc)=2,4 respectively for long-ranged and short-ranged elasticity) we show that
      the field theory for the center of mass reduces to the motion of a point particle
      in a random-force landscape, which is itself a random walk [Alessandro, Beatrice,
      Bertotti, and Montorsi (ABBM) model]. Furthermore, the full spatial dependence of
      the velocity correlations is described by the Brownian-force model (BFM) where
      each point of the interface sees an independent Brownian-force landscape. Both
      ABBM and BFM can be solved exactly in any dimension d (for monotonous driving) by
      summing tree graphs, equivalent to solving a (nonlinear) instanton equation. We
      focus on the limit of slow uniform driving. This tree approximation is the mean
      field theory (MFT) for realistic interfaces in short-ranged disorder, up to the
      renormalization of two parameters at d=d(uc). We calculate a number of
      observables of direct experimental interest: Both for the center of mass, and for
      a given Fourier mode q, we obtain various correlations and probability
      distribution functions (PDF's) of the velocity inside an avalanche, as well as
      the avalanche shape and its fluctuations (second shape). Within MFT we find that
      velocity correlations at nonzero q are asymmetric under time reversal. Next we
      calculate, beyond MFT, i.e., including loop corrections, the one-time PDF of the
      center-of-mass velocity u[over .] for dimension d<d(uc). The singularity at small
      velocity P(u[over .])~1/u[over .](a) is substantially reduced from a=1 (MFT) to
      a=1-2/9(4-d)+... (short-ranged elasticity) and a=1-4/9(2-d)+... (long-ranged
      elasticity). We show how the dynamical theory recovers the avalanche-size
      distribution, and how the instanton relates to the response to an infinitesimal
      step in the force.

PMID- 24032775
TI  - Commutative law for products of infinitely large isotropic random matrices.
AB  - Ensembles of isotropic random matrices are defined by the invariance of the
      probability measure under the left (and right) multiplication by an arbitrary
      unitary matrix. We show that the multiplication of large isotropic random
      matrices is spectrally commutative and self-averaging in the limit of infinite
      matrix size N->infinity. The notion of spectral commutativity means that the
      eigenvalue density of a product ABC... of such matrices is independent of the
      order of matrix multiplication, for example, the matrix ABCD has the same
      eigenvalue density as ADCB. In turn, the notion of self-averaging means that the
      product of n independent but identically distributed random matrices, which we
      symbolically denote by AAA..., has the same eigenvalue density as the
      corresponding power A(n) of a single matrix drawn from the underlying matrix
      ensemble. For example, the eigenvalue density of ABCCABC is the same as that of
      A(2)B(2)C(3). We also discuss the singular behavior of the eigenvalue and
      singular value densities of isotropic matrices and their products for small
      eigenvalues lambda->0. We show that the singularities at the origin of the
      eigenvalue density and of the singular value density are in one-to-one
      correspondence in the limit N->infinity: The eigenvalue density of an isotropic
      random matrix has a power-law singularity at the origin ~|lambda|(-s) with a
      power sepsilon(0,2) when and only when the density of its singular values has a
      power-law singularity ~lambda(-sigma) with a power sigma=s/(4-s). These results
      are obtained analytically in the limit N->infinity. We supplement these results
      with numerical simulations for large but finite N and discuss finite-size effects
      for the most common ensembles of isotropic random matrices.

PMID- 24032776
TI  - Microscopic theory of anomalous diffusion based on particle interactions.
AB  - We present a master equation formulation based on a Markovian random walk model
      that exhibits subdiffusion, classical diffusion, and superdiffusion as a function
      of a single parameter. The nonclassical diffusive behavior is generated by
      allowing for interactions between a population of walkers. At the macroscopic
      level, this gives rise to a nonlinear Fokker-Planck equation. The diffusive
      behavior is reflected not only in the mean squared displacement
      [<r(2)(t)>~t(gamma) with 0<gamma<=1.5] but also in the existence of self-similar
      scaling solutions of the Fokker-Planck equation. We give a physical
      interpretation of sub- and superdiffusion in terms of the attractive and
      repulsive interactions between the diffusing particles and we discuss
      analytically the limiting values of the exponent gamma. Simulations based on the
      master equation are shown to be in agreement with the analytical solutions of the
      nonlinear Fokker-Planck equation in all three diffusion regimes.

PMID- 24032777
TI  - Crystal growth inside an octant.
AB  - We study crystal growth inside an infinite octant on a cubic lattice. The growth
      proceeds through the deposition of elementary cubes into inner corners. After
      rescaling by the characteristic size, the interface becomes progressively more
      deterministic in the long-time limit. Utilizing known results for the crystal
      growth inside a two-dimensional corner, we propose a hyperbolic partial
      differential equation for the evolution of the limiting shape. This equation is
      interpreted as a Hamilton-Jacobi equation, which helps in finding an analytical
      solution. Simulations of the growth process are in excellent agreement with
      analytical predictions. We then study the evolution of the subleading correction
      to the volume of the crystal, the asymptotic growth of the variance of the volume
      of the crystal, and the total number of inner and outer corners. We also show how
      to generalize the results to arbitrary spatial dimension. 

PMID- 24032778
TI  - Typical and rare fluctuations in nonlinear driven diffusive systems with
      dissipation.
AB  - We consider fluctuations of the dissipated energy in nonlinear driven diffusive
      systems subject to bulk dissipation and boundary driving. With this aim, we
      extend the recently introduced macroscopic fluctuation theory to nonlinear driven
      dissipative media, starting from the fluctuating hydrodynamic equations
      describing the system mesoscopic evolution. Interestingly, the action associated
      with a path in mesoscopic phase space, from which large-deviation functions for
      macroscopic observables can be derived, has the same simple form as in
      nondissipative systems. This is a consequence of the quasielasticity of
      microscopic dynamics, required in order to have a nontrivial competition between
      diffusion and dissipation at the mesoscale. Euler-Lagrange equations for the
      optimal density and current fields that sustain an arbitrary dissipation
      fluctuation are also derived. A perturbative solution thereof shows that the
      probability distribution of small fluctuations is always Gaussian, as expected
      from the central limit theorem. On the other hand, strong separation from the
      Gaussian behavior is observed for large fluctuations, with a distribution which
      shows no negative branch, thus violating the Gallavotti-Cohen fluctuation
      theorem, as expected from the irreversibility of the dynamics. The dissipation
      large-deviation function exhibits simple and general scaling forms for weakly and
      strongly dissipative systems, with large fluctuations favored in the former case
      but heavily suppressed in the latter. We apply our results to a general class of
      diffusive lattice models for which dissipation, nonlinear diffusion, and driving
      are the key ingredients. The theoretical predictions are compared to extensive
      numerical simulations of the microscopic models, and excellent agreement is
      found. Interestingly, the large-deviation function is in some cases nonconvex
      beyond some dissipation. These results show that a suitable generalization of
      macroscopic fluctuation theory is capable of describing in detail the fluctuating
      behavior of nonlinear driven dissipative media. 

PMID- 24032779
TI  - Ground states of an Ising model on an extended Shastry-Sutherland lattice and the
      1/2-magnetization plateau in some rare-earth-metal tetraborides.
AB  - A complete solution of the ground-state problem for an Ising model on the Shastry
      Sutherland lattice with an additional interaction along the diagonals of "empty"
      squares in an applied magnetic field is presented. A rigorous proof is given that
      this interaction gives rise to a plateau at one-half of the saturation
      magnetization. Such a fractional plateau has been observed in some rare-earth
      metal tetraborides, in particular in strong Ising magnets ErB(4) (where it is the
      only one) and TmB(4) (where it is the broadest one), but its origin has remained
      unclear. Our study sheds new light on the solution of this problem.

PMID- 24032780
TI  - Correlation functions in liquids and crystals: free-energy functional and liquid
      to-crystal transition.
AB  - A free-energy functional for a crystal that contains both the symmetry-conserved
      and symmetry-broken parts of the direct pair-correlation function has been used
      to investigate the crystallization of fluids in three dimensions. The symmetry
      broken part of the direct pair-correlation function has been calculated using a
      series in ascending powers of the order parameters and which contains three- and
      higher-body direct correlation functions of the isotropic phase. It is shown that
      a very accurate description of freezing transitions for a wide class of
      potentials is found by considering the first two terms of this series. The
      results found for freezing parameters including the structure of the frozen phase
      for fluids interacting via the inverse power potential u(r)=epsilon(sigma/r)(n)
      for n ranging from 4 to infinity are in very good agreement with simulation
      results. It is found that for n>6.5 the fluid freezes into a face-centered cubic
      (fcc) structure while for n<=6 the body-centered cubic (bcc) structure is
      preferred. The fluid-bcc-fcc triple point is found to be at 1/n=0.158, which is
      in good agreement with simulation result.

PMID- 24032781
TI  - Momentum distribution functions in ensembles: the inequivalence of
      microcannonical and canonical ensembles in a finite ultracold system.
AB  - It is demonstrated in many thermodynamic textbooks that the equivalence of the
      different ensembles is achieved in the thermodynamic limit. In this present work
      we discuss the inequivalence of microcanonical and canonical ensembles in a
      finite ultracold system at low energies. We calculate the microcanonical momentum
      distribution function (MDF) in a system of identical fermions (bosons). We find
      that the microcanonical MDF deviates from the canonical one, which is the Fermi
      Dirac (Bose-Einstein) function, in a finite system at low energies where the
      single-particle density of states and its inverse are finite. 

PMID- 24032782
TI  - Critical manifold of globally coupled overdamped anharmonic oscillators driven by
      additive Gaussian white noise.
AB  - We consider an infinite array of globally coupled overdamped anharmonic
      oscillators subject to additive Gaussian white noise which is closely related to
      the mean field Phi(4)-Ginzburg-Landau model. We prove the existence of a well
      behaved critical manifold in the parameter space which separates a symmetric
      phase from a symmetry broken phase. Given two of the system parameters, there is
      a unique critical value of the third. The proof exploits that the critical
      control parameter a(c) is bounded by its limit values for weak and strong noise.
      In these limits, the mechanism of symmetry breaking differs. For weak noise, the
      distribution is Gaussian and the symmetry is broken as the whole distribution is
      shifted in either the positive or the negative direction. For strong noise, there
      is a symmetric double-peak distribution and the symmetry is broken as the weights
      of the peaks become different. We derive an ordinary differential equation whose
      solution describes the critical manifold. Using a series ansatz to solve this
      differential equation, we determine the critical manifold for weak and strong
      noise and compare it to numerical results. We derive analytic expressions for the
      order parameter and the susceptibility close to the critical manifold.

PMID- 24032783
TI  - Non-Gaussian propagator for elephant random walks.
AB  - For almost a decade the consensus has held that the random walk propagator for
      the elephant random walk (ERW) model is a Gaussian. Here we present strong
      numerical evidence that the propagator is, in general, non-Gaussian and, in fact,
      non-Levy. Motivated by this surprising finding, we seek a second, non-Gaussian
      solution to the associated Fokker-Planck equation. We prove mathematically, by
      calculating the skewness, that the ERW Fokker-Planck equation has a non-Gaussian
      propagator for the superdiffusive regime. Finally, we discuss some unusual
      aspects of the propagator in the context of higher order terms needed in the
      Fokker-Planck equation. 

PMID- 24032784
TI  - Invariance in the recurrence of large returns and the validation of models of
      price dynamics.
AB  - Starting from a robust, nonparametric definition of large returns ("excursions"),
      we study the statistics of their occurrences, focusing on the recurrence process.
      The empirical waiting-time distribution between excursions is remarkably
      invariant to year, stock, and scale (return interval). This invariance is related
      to self-similarity of the marginal distributions of returns, but the excursion
      waiting-time distribution is a function of the entire return process and not just
      its univariate probabilities. Generalized autoregressive conditional
      heteroskedasticity (GARCH) models, market-time transformations based on volume or
      trades, and generalized (Levy) random-walk models all fail to fit the statistical
      structure of excursions. 

PMID- 24032785
TI  - Zero-temperature random-field Ising model on a bilayered Bethe lattice.
AB  - The zero-temperature random-field Ising model is solved analytically for
      magnetization versus external field for a bilayered Bethe lattice. The mechanisms
      of infinite avalanches which are observed for small values of disorder are
      established. The effects of variable interlayer interaction strengths on infinite
      avalanches are investigated. The spin-field correlation length is calculated and
      its critical behavior is discussed. Direct Monte Carlo simulations of spin-flip
      dynamics are shown to support the analytical findings. We find, paradoxically,
      that a reduction of the interlayer bond strength can cause a phase transition
      from a regime with continuous magnetization reversal to a regime where
      magnetization exhibits a discontinuity associated with an infinite avalanche.
      This effect is understood in terms of the proposed mechanisms for the infinite
      avalanche. 

PMID- 24032786
TI  - Optimal sensor selection for noisy binary detection in stochastic pooling
      networks.
AB  - Stochastic Pooling Networks (SPNs) are a useful model for understanding and
      explaining how naturally occurring encoding of stochastic processes can occur in
      sensor systems ranging from macroscopic social networks to neuron populations and
      nanoscale electronics. Due to the interaction of nonlinearity, random noise, and
      redundancy, SPNs support various unexpected emergent features, such as
      suprathreshold stochastic resonance, but most existing mathematical results are
      restricted to the simplest case where all sensors in a network are identical.
      Nevertheless, numerical results on information transmission have shown that in
      the presence of independent noise, the optimal configuration of a SPN is such
      that there should be partial heterogeneity in sensor parameters, such that the
      optimal solution includes clusters of identical sensors, where each cluster has
      different parameter values. In this paper, we consider a SPN model of a binary
      hypothesis detection task and show mathematically that the optimal solution for a
      specific bound on detection performance is also given by clustered heterogeneity,
      such that measurements made by sensors with identical parameters either should
      all be excluded from the detection decision or all included. We also derive an
      algorithm for numerically finding the optimal solution and illustrate its utility
      with several examples, including a model of parallel sensory neurons with Poisson
      firing characteristics. 

PMID- 24032787
TI  - Sampling fractional Brownian motion in presence of absorption: a Markov chain
      method.
AB  - We numerically study fractional Brownian motion (fBm) with an absorbing boundary
      at the origin for selected values of the Hurst exponent Hepsilon[0,1]. Using a
      Monte Carlo sampling technique, we are able to numerically generate these fBm
      processes at discrete times for up to 10(7) time steps, even for values as small
      as H=1/4. The results are compatible with previous analytical results that
      suggest that the distribution of (rescaled) endpoints y follow a power law
      P(+)(y)~y(phi) with phi=(1-H)/H, even for small values of H. Furthermore, for
      H=0.5 we study analytically the finite-length corrections to first order, namely
      a plateau of P(+)(y) for y->0 which decreases with increasing process length.
      These corrections are compatible with our numerical results.

PMID- 24032788
TI  - Diffusion of small particles in a solid polymeric medium.
AB  - We analyze diffusion of small particles in a solid polymeric medium taking into
      account a short-range particle-polymer interaction. The system is modeled by a
      particle diffusion on a ternary lattice where the sites occupied by polymer
      segments are blocked, the ones forming the hull of the chains correspond to the
      places at which the interaction takes place, and the rest are voids, in which the
      diffusion is free. In the absence of interaction the diffusion coefficient shows
      only a weak dependence on the polymer chain length and its behavior strongly
      resembles the usual site percolation. In the presence of interactions the
      diffusion coefficient (and especially its temperature dependence) shows a
      nontrivial behavior depending on the sign of interaction and on whether the voids
      and the hulls of the chains percolate or not. The temperature dependence may be
      Arrhenius-like or strongly non-Arrhenius, depending on parameters. The analytical
      results obtained within the effective medium approximation are in qualitative
      agreement with those of Monte Carlo simulations. 

PMID- 24032789
TI  - Nonequilibrium density matrix for quantum transport: Hershfield approach as a
      McLennan-Zubarev form of the statistical operator.
AB  - In this paper, we formally demonstrate that the nonequilibrium density matrix
      developed by Hershfield for the steady state has the form of a McLennan-Zubarev
      nonequilibrium ensemble. The correction term in this pseudoequilibrium Gibbs-like
      ensemble is directly related to the entropy production in the quantum open
      system. The fact that both methods state that a nonequilibrium steady state can
      be mapped onto a pseudoequilibrium, permits us to develop nonequilibrium
      quantities from formal expressions equivalent to the equilibrium case. We provide
      an example: the derivation of a nonequilibrium distribution function for the
      electron population in a scattering region in the context of quantum transport. 

PMID- 24032790
TI  - Renormalization group calculations for wetting transitions of infinite order and
      continuously varying order: local interface Hamiltonian approach.
AB  - We study the effect of thermal fluctuations on the wetting phase transitions of
      infinite order and of continuously varying order, recently discovered within a
      mean-field density-functional model for three-phase equilibria in systems with
      short-range forces and a two-component order parameter. Using linear functional
      renormalization group calculations within a local interface Hamiltonian approach,
      we show that the infinite-order transitions are robust. The exponential
      singularity (implying 2-alpha(s)=infinity) of the surface free energy excess at
      infinite-order wetting as well as the precise algebraic divergence (with beta(s)=
      1) of the wetting layer thickness are not modified as long as omega<2, with omega
      the dimensionless wetting parameter that measures the strength of thermal
      fluctuations. The interface width diverges algebraically and universally (with
      nu([perpendicular])=1/2). In contrast, the nonuniversal critical wetting
      transitions of finite but continuously varying order are modified when thermal
      fluctuations are taken into account, in line with predictions from earlier
      calculations on similar models displaying weak, intermediate, and strong
      fluctuation regimes.

PMID- 24032791
TI  - Diverging fluctuations in a spatial five-species cyclic dominance game.
AB  - A five-species predator-prey model is studied on a square lattice where each
      species has two prey and two predators on the analogy to the rock-paper-scissors
      lizard-Spock game. The evolution of the spatial distribution of species is
      governed by site exchange and invasion between the neighboring predator-prey
      pairs, where the cyclic symmetry can be characterized by two different invasion
      rates. The mean-field analysis has indicated periodic oscillations in the species
      densities with a frequency becoming zero for a specific ratio of invasion rates.
      When varying the ratio of invasion rates, the appearance of this zero-eigenvalue
      mode is accompanied by neutrality between the species associations. Monte Carlo
      simulations of the spatial system reveal diverging fluctuations at a specific
      invasion rate, which can be related to the vanishing dominance between all pairs
      of species associations. 

PMID- 24032792
TI  - Efficiency of harvesting energy from colored noise by linear oscillators.
AB  - We investigate the performance of a linear electromechanical oscillator as an
      energy harvester of finite-bandwidth random vibrations. We derive exact
      analytical expressions for the net electrical power and the efficiency of the
      conversion of the power supplied by the noise into electrical power for arbitrary
      colored noise. We apply our results to the important case of exponentially
      correlated noise and discuss the tuning of parameters to achieve good performance
      of the device. 

PMID- 24032793
TI  - Particle dynamics in two-dimensional random-energy landscapes: experiments and
      simulations.
AB  - The dynamics of individual colloidal particles in random potential energy
      landscapes was investigated experimentally and by Monte Carlo simulations. The
      value of the potential at each point in the two-dimensional energy landscape
      follows a Gaussian distribution. The width of the distribution, and hence the
      degree of roughness of the energy landscape, was varied and its effect on the
      particle dynamics studied. This situation represents an example of Brownian
      dynamics in the presence of disorder. In the experiments, the energy landscapes
      were generated optically using a holographic setup with a spatial light
      modulator, and the particle trajectories were followed by video microscopy. The
      dynamics is characterized using, e.g., the time-dependent diffusion coefficient,
      the mean squared displacement, the van Hove function, and the non-Gaussian
      parameter. In both experiments and simulations the dynamics is initially
      diffusive, showing an extended subdiffusive regime at intermediate times before
      diffusive motion is recovered at very long times. The dependence of the long-time
      diffusion coefficient on the width of the Gaussian distribution agrees with
      theoretical predictions. Compared to the dynamics in a one-dimensional potential
      energy landscape, the localization at intermediate times is weaker and the
      diffusive regime at long times reached earlier, which is due to the possibility
      to avoid local maxima in two-dimensional energy landscapes. 

PMID- 24032794
TI  - Random-matrix-theory approach to mesoscopic fluctuations of heat current.
AB  - We consider an ensemble of fully connected networks of N oscillators coupled
      harmonically with random springs and show, using random-matrix-theory
      considerations, that both the average phonon heat current and its variance are
      scale invariant and take universal values in the large N limit. These anomalous
      mesoscopic fluctuations is the hallmark of strong correlations between normal
      modes. 

PMID- 24032795
TI  - Dynamics of an electric dipole moment in a stochastic electric field.
AB  - The mean-field dynamics of an electric dipole moment in a deterministic and a
      fluctuating electric field is solved to obtain the average over fluctuations of
      the dipole moment and the angular momentum as a function of time for a Gaussian
      white-noise stochastic electric field. The components of the average electric
      dipole moment and the average angular momentum along the deterministic electric
      field direction do not decay to zero, despite fluctuations in all three
      components of the electric field. This is in contrast to the decay of the average
      over fluctuations of a magnetic moment in a stochastic magnetic field with
      Gaussian white noise in all three components. The components of the average
      electric dipole moment and the average angular momentum perpendicular to the
      deterministic electric-field direction oscillate with time but decay to zero, and
      their variance grows with time. 

PMID- 24032796
TI  - Normal dynamic scaling in the class of the nonlinear molecular-beam-epitaxy
      equation.
AB  - The scaling of local height fluctuations is studied numerically in lattice growth
      models of the class of the nonlinear stochastic equation of Villain-Lai-Das Sarma
      (VLDS) in substrate dimensions d=1 and 2. In d=1, the average local slopes of the
      conserved restricted solid-on-solid (CRSOS) models converge to a finite value in
      the long-time limit, with power-law corrections in time whose exponents are close
      to 0.1. Other VLDS models in d=1, such as that of Das Sarma and Tamborenea, show
      a divergence of local slopes up to 10(6) monolayers, typical of anomalous
      roughening, but a comparison of roughness distributions shows that they scale as
      the linear fourth-order growth equation in those time scales. Normal scaling is
      also obtained in a modified VLDS equation with instability suppression, in
      contrast to recent numerical works. In d=2, a CRSOS model and a model with
      lateral aggregation of diffusing particles show normal scaling of the local
      slopes, also with small correction exponents. These results consistently show
      that the VLDS class has normal dynamic scaling in d=1 and 2, in agreement with
      the theoretical predictions of Phys. Rev. Lett. 94, 166103 (2005), and they show
      that the apparently anomalous features observed in previous works are effects of
      large scaling correction terms or crossover effects.

PMID- 24032797
TI  - Single-particle fluctuations and directional correlations in driven hard-sphere
      glasses.
AB  - Via event-driven molecular dynamics simulations and experiments, we study the
      packing-fraction and shear-rate dependence of single-particle fluctuations and
      dynamic correlations in hard-sphere glasses under shear. At packing fractions
      above the glass transition, correlations increase as shear rate decreases: the
      exponential tail in the distribution of single-particle jumps broadens and
      dynamic four-point correlations increase. Interestingly, however, upon decreasing
      the packing fraction, a broadening of the exponential tail is also observed,
      while dynamic heterogeneity is shown to decrease. An explanation for this
      behavior is proposed in terms of a competition between shear and thermal
      fluctuations. Building upon our previous studies [Chikkadi et al., Europhys.
      Lett. 100, 56001 (2012)], we further address the issue of anisotropy of the
      dynamic correlations. 

PMID- 24032798
TI  - Random matrix ensemble with random two-body interactions in the presence of a
      mean field for spin-one boson systems.
AB  - For bosons carrying spin-one degree of freedom, we introduce an embedded Gaussian
      orthogonal ensemble of random matrices generated by random two-body interactions
      in the presence of a mean field that is spin (S) scalar [called BEGOE(1+2)-S1].
      Embedding algebra for the ensemble, for m bosons in Omega number of single
      particle levels (each triply degenerate), is U(3Omega)?G?G1?SO(3) with SO(3)
      generating the spin S. A method for constructing the ensemble for a given
      (Omega,m,S) has been developed. Numerical calculations show that (i) the form of
      the fixed-(m, S) density of states is close to a Gaussian; (ii) for a strong
      enough interaction, level fluctuations follow GOE; (iii) fluctuation in energy
      centroids is large; and (iv) spectral widths are nearly constant with respect to
      S for S<S(max)/2. Moreover, we identify two different pairing symmetry algebras
      in the space defined by BEGOE(1+2)-S1 and numerical results show that random
      interactions generate ground states with maximal value for the pair expectation
      value.

PMID- 24032799
TI  - Evolution equation for tagged-particle density and correlations in single-file
      diffusion.
AB  - We derive and study a theoretical description for single-file diffusion, i.e.,
      diffusion in a one-dimensional lattice of particles with hard core interaction.
      It is well known that for this system a tagged particle has anomalous diffusion
      for long times. The novelty of the present approach is that it allows for the
      derivation of correlations between a tagged particle and other particles of the
      system at a given distance with empty sites in between. The behavior of the
      correlation gives deeper insights into the processes involved. The numerical
      integration of differential equations are in good agreement with Monte Carlo
      simulations. 

PMID- 24032800
TI  - Bose-Einstein condensation of light: general theory.
AB  - A theory of Bose-Einstein condensation of light in a dye-filled optical
      microcavity is presented. The theory is based on the hierarchical maximum entropy
      principle and allows one to investigate the fluctuating behavior of the photon
      gas in the microcavity for all numbers of photons, dye molecules, and excitations
      at all temperatures, including the whole critical region. The master equation
      describing the interaction between photons and dye molecules in the microcavity
      is derived and the equivalence between the hierarchical maximum entropy principle
      and the master equation approach is shown. The cases of a fixed mean total photon
      number and a fixed total excitation number are considered, and a much sharper,
      nonparabolic onset of a macroscopic Bose-Einstein condensation of light in the
      latter case is demonstrated. The theory does not use the grand canonical
      approximation, takes into account the photon polarization degeneracy, and exactly
      describes the microscopic, mesoscopic, and macroscopic Bose-Einstein condensation
      of light. Under certain conditions, it predicts sub-Poissonian statistics of the
      photon condensate and the polarized photon condensate, and a universal relation
      takes place between the degrees of second-order coherence for these condensates.
      In the macroscopic case, there appear a sharp jump in the degrees of second-order
      coherence, a sharp jump and kink in the reduced standard deviations of the
      fluctuating numbers of photons in the polarized and whole condensates, and a
      sharp peak, a cusp, of the Mandel parameter for the whole condensate in the
      critical region. The possibility of nonclassical light generation in the
      microcavity with the photon Bose-Einstein condensate is predicted. 

PMID- 24032801
TI  - Phase diagram of a cyclic predator-prey model with neutral-pair exchange.
AB  - In this paper we obtain the phase diagram of a four-species predator-prey lattice
      model by using the proposed gradient method. We consider cyclic transitions
      between consecutive states, representing invasion or predation, and allowed the
      exchange between neighboring neutral pairs. By applying a gradient in the
      invasion rate parameter one can see, in the same simulation, the presence of two
      symmetric absorbing phases, composed by neutral pairs, and an active phase that
      includes all four species. In this sense, the study of a single-valued interface
      and its fluctuations give the critical point of the irreversible phase transition
      and the corresponding universality classes. Also, the consideration of a
      multivalued interface and its fluctuations bring the percolation threshold. We
      show that the model presents two lines of irreversible first-order phase
      transition between the two absorbing phases and the active phase. Depending on
      the value of the system parameters, these lines can converge into a triple point,
      which is the beginning of a first-order irreversible line between the two
      absorbing phases, or end in two critical points belonging to the directed
      percolation universality class. Standard simulations for some characteristic
      values of the parameters confirm the order of the transitions as determined by
      the gradient method. Besides, below the triple point the model presents two
      standard percolation lines in the active phase and above a first-order
      percolation transition as already found in other similar models. 

PMID- 24032802
TI  - Force fluctuations in stretching a tethered polymer.
AB  - The recently proposed fluctuation relation in unfolding forces [Phys. Rev. E 84,
      060101(R) (2011)] is reexamined taking into account the explicit time dependence
      of the force distribution. The stretching of a tethered Rouse polymer is exactly
      solved and the ratio of the probabilities of positive to negative forces is shown
      to be an exponential in force. Extensive steered molecular dynamics simulations
      of unfolding of deca alanine peptide confirm the form of fluctuation relation
      proposed earlier, but with explicit correct time dependence of unfolding forces
      taken into account. From exact calculations and simulations, a linear dependence
      of the constant in the exponential of the fluctuation relation on average
      unfolding forces and inverse temperature is proposed. 

PMID- 24032803
TI  - Renormalization group flow of hexatic membranes.
AB  - We investigate hexatic membranes embedded in Euclidean D-dimensional space using
      a reparametrization invariant formulation combined with exact renormalization
      group equations. An XY model coupled to a fluid membrane, when integrated out,
      induces long-range interactions between curvatures described by a Polyakov term
      in the effective action. We evaluate the contributions of this term to the
      running surface tension, bending, and Gaussian rigidities in the approximation of
      vanishing disinclination (vortex) fugacity. We find a non-Gaussian fixed point
      where the membrane is crinkled and has a nontrivial fractal dimension. 

PMID- 24032804
TI  - Anomalous diffusion in the evolution of soccer championship scores: real data,
      mean-field analysis, and an agent-based model.
AB  - Statistics of soccer tournament scores based on the double round robin system of
      several countries are studied. Exploring the dynamics of team scoring during
      tournament seasons from recent years we find evidences of superdiffusion. A mean
      field analysis results in a drift velocity equal to that of real data but in a
      different diffusion coefficient. Along with the analysis of real data we present
      the results of simulations of soccer tournaments obtained by an agent-based model
      which successfully describes the final scoring distribution [da Silva et al.,
      Comput. Phys. Commun. 184, 661 (2013)]. Such model yields random walks of scores
      over time with the same anomalous diffusion as observed in real data. 

PMID- 24032805
TI  - From local force-flux relationships to internal dissipations and their impact on
      heat engine performance: the illustrative case of a thermoelectric generator.
AB  - We present an in-depth analysis of the sometimes understated role of the
      principle of energy conservation in linear irreversible thermodynamics. Our case
      study is that of a thermoelectric generator (TEG), which is a heat engine of
      choice in irreversible thermodynamics, owing to the coupling between the
      electrical and heat fluxes. We show why Onsager's reciprocal relations must be
      considered locally and how internal dissipative processes emerge from the
      extension of these relations to a global scale: The linear behavior of a heat
      engine at the local scale is associated with a dissipation process that must
      partake in the global energy balance. We discuss the consequences of internal
      dissipations on the so-called efficiency at maximum power, in the light of our
      comparative analyses of exoreversibility and endoreversibility on the one hand
      and of two classes of heat engines, autonomous and periodically driven, on the
      other hand. Finally, basing our analysis on energy conservation, we also discuss
      recent works which claim the possibility to overcome the traditional boundaries
      on efficiency imposed by finite-time thermodynamics in thermoelectric systems
      with broken time-reversal symmetry; this we do by introducing a "thermal"
      thermopower and an "electrical" thermopower which permits an analysis of the
      thermoelectric response of the TEG considering a possible dissymmetry between the
      electrical/thermal and the thermal/electrical couplings. 

PMID- 24032806
TI  - Anomalous velocity distributions in active Brownian suspensions.
AB  - Large-scale simulations and analytical theory have been combined to obtain the
      nonequilibrium velocity distribution, f(v), of randomly accelerated particles in
      suspension. The simulations are based on an event-driven algorithm, generalized
      to include friction. They reveal strongly anomalous but largely universal
      distributions, which are independent of volume fraction and collision processes,
      which suggests a one-particle model should capture all the essential features. We
      have formulated this one-particle model and solved it analytically in the limit
      of strong damping, where we find that f(v) decays as 1/v for multiple decades,
      eventually crossing over to a Gaussian decay for the largest velocities. Many
      particle simulations and numerical solution of the one-particle model agree for
      all values of the damping. 

PMID- 24032807
TI  - Critical behavior of the ideal-gas Bose-Einstein condensation in the Apollonian
      network.
AB  - We show that the ideal Boson gas displays a finite-temperature Bose-Einstein
      condensation transition in the complex Apollonian network exhibiting scale-free,
      small-world, and hierarchical properties. The single-particle tight-binding
      Hamiltonian with properly rescaled hopping amplitudes has a fractal-like energy
      spectrum. The energy spectrum is analytically demonstrated to be generated by a
      nonlinear mapping transformation. A finite-size scaling analysis over several
      orders of magnitudes of network sizes is shown to provide precise estimates for
      the exponents characterizing the condensed fraction, correlation size, and
      specific heat. The critical exponents, as well as the power-law behavior of the
      density of states at the bottom of the band, are similar to those of the ideal
      Boson gas in lattices with spectral dimension d(s)=2ln(3)/ln(9/5)~/=3.74.

PMID- 24032808
TI  - Continuum percolation of overlapping disks with a distribution of radii having a
      power-law tail.
AB  - We study the continuum percolation problem of overlapping disks with a
      distribution of radii having a power-law tail; the probability that a given disk
      has a radius between R and R+dR is proportional to R(-(a+1)), where a>2. We show
      that in the low-density nonpercolating phase, the two-point function shows a
      power-law decay with distance, even at arbitrarily low densities of the disks,
      unlike the exponential decay in the usual percolation problem. As in the problem
      of fluids with long-range interaction, we argue that in our problem, the critical
      exponents take their short-range values for a>3-eta(sr) whereas they depend on a
      for a<3-eta(sr) where eta(sr) is the anomalous dimension for the usual
      percolation problem. The mean-field regime obtained in the fluid problem
      corresponds to the fully covered regime, a<=2, in the percolation problem. We
      propose an approximate renormalization scheme to determine the correlation length
      exponent nu and the percolation threshold. We carry out Monte Carlo simulations
      and determine the exponent nu as a function of a. The determined values of nu
      show that it is independent of the parameter a for a>3-eta(sr) and is equal to
      that for the lattice percolation problem, whereas nu varies with a for 2<a<3
      eta(sr). We also determine the percolation threshold of the system as a function
      of the parameter a.

PMID- 24032809
TI  - Helices in the wake of precipitation fronts.
AB  - A theoretical study of the emergence of helices in the wake of precipitation
      fronts is presented. The precipitation dynamics is described by the Cahn-Hilliard
      equation and the fronts are obtained by quenching the system into a linearly
      unstable state. Confining the process onto the surface of a cylinder and using
      the pulled-front formalism, our analytical calculations show that there are front
      solutions that propagate into the unstable state and leave behind a helical
      structure. We find that helical patterns emerge only if the radius of the
      cylinder R is larger than a critical value R>R(c), in agreement with recent
      experiments.

PMID- 24032810
TI  - Variational principle for fractional kinetics and the Levy Ansatz.
AB  - A variational principle is developed for fractional kinetics based on the
      auxiliary-field formalism. It is applied to the Fokker-Planck equation with
      spatiotemporal fractionality, and a variational solution is obtained with the
      help of the Levy Ansatz. It is shown how the whole range from subdiffusion to
      superdiffusion is realized by the variational solution as a competing effect
      between the long waiting time and the long jump. The motion of the center of the
      probability distribution is also analyzed in the case of a periodic drift. 

PMID- 24032811
TI  - Nonequilibrium work by charge control in a Josephson junction.
AB  - We consider a single Josephson junction in the presence of time varying gate
      charge, and examine the nonequilibrium work done by the charge control in the
      framework of fluctuation theorems. Assuming first a high quality junction with
      negligible Ohmic current, we obtain the probability distribution functions of the
      work and confirm the Crooks relation to give the estimation of the free energy
      changes DeltaF=0. The reliability of DeltaF estimated from the Jarzynksi equality
      is crucially dependent on protocol parameters, while the Bennett's acceptance
      ratio method yields consistently DeltaF=0. We examine the behaviors of the work
      average and point out its relation to heat and entropy production associated with
      the circuit control. Finally considering finite tunnel resistance we discuss
      dissipation effects on the work statistics. 

PMID- 24032812
TI  - Nonexistence of equilibrium states at absolute negative temperatures.
AB  - We show that states of macroscopic systems with purported absolute negative
      temperatures are not stable under small, yet arbitrary, perturbations. We prove
      the previous statement using the fact that, in equilibrium, the entropy takes its
      maximum value. We discuss that, while Ramsey theoretical reformulation of the
      second law for systems with negative temperatures is logically correct, it must
      be a priori assumed that those states are in thermodynamic equilibrium. Since we
      argue that those states cannot occur, reversible processes are impossible, and,
      thus, Ramsey identification of absolute negative temperatures is untenable. 

PMID- 24032813
TI  - Statistics of superior records.
AB  - We study statistics of records in a sequence of random variables. These identical
      and independently distributed variables are drawn from the parent distribution
      rho. The running record equals the maximum of all elements in the sequence up to
      a given point. We define a superior sequence as one where all running records are
      above the average record expected for the parent distribution rho. We find that
      the fraction of superior sequences S(N) decays algebraically with sequence length
      N, S(N)~N(-beta) in the limit N->infinity. Interestingly, the decay exponent beta
      is nontrivial, being the root of an integral equation. For example, when rho is a
      uniform distribution with compact support, we find beta=0.450265. In general, the
      tail of the parent distribution governs the exponent beta. We also consider the
      dual problem of inferior sequences, where all records are below average, and find
      that the fraction of inferior sequences I(N) decays algebraically, albeit with a
      different decay exponent, I(N)~N(-alpha). We use the above statistical measures
      to analyze earthquake data.

PMID- 24032814
TI  - Fluctuation theorem for hidden entropy production.
AB  - Elimination of seemingly unnecessary variables in Markovian models may cause a
      difference in the value of irreversible entropy production between the original
      and reduced dynamics. We show that such difference, which we call the hidden
      entropy production, obeys an integral fluctuation theorem if all variables are
      time-reversal invariant, or if the density function is symmetric with respect to
      the change of sign of the time-reversal antisymmetric variables. The theorem has
      wide applicability, since the proposed condition is mostly satisfied in the case
      where the hidden fast variables are equilibrated. The main consequence of this
      theorem is that the entropy production decreases by the coarse-graining
      procedure. By contrast, in the case where a stochastic process is obtained by
      coarse-graining a deterministic and reversible dynamics, the entropy production
      may increase, implying that the integral fluctuation theorem should not hold for
      such reductions. We reveal, with an explicit example, that the nonequilibrated
      time-reversal antisymmetric variables play a crucial role in distinguishing these
      two cases, thus guaranteeing the consistency of the presented theorem. 

PMID- 24032815
TI  - Quasiparticle parametrization of mean fields, Galilei invariance, and universal
      conserving response functions.
AB  - The general possible form of mean-field parametrization in a running frame in
      terms of current, energy, and density functionals is examined under the
      restrictions of Galilean invariance. It is found that only two density-dependent
      parameters remain which are usually condensed in a position-dependent effective
      mass and the self-energy formed by current and mass. The position-dependent mass
      induces a position-dependent local current, which is identified for different
      nonlinear frames. In a second step the response to an external perturbation and
      relaxation towards a local equilibrium is investigated. The response function is
      found to be universal in the sense that the actual parametrization of the local
      equilibrium does not matter and is eliminated from the theory due to the
      conservation laws. The explicit form of the response with respect to density,
      momentum, and energy is derived. The compressibility sum rule as well as the sum
      rule by first- and third-order frequency moments are proved analytically to be
      fulfilled simultaneously. The results are presented for Bose or Fermi systems in
      one, two, and three dimensions. 

PMID- 24032816
TI  - Dynamics of multiphase systems with complex microstructure. I. Development of the
      governing equations through nonequilibrium thermodynamics.
AB  - In this paper we present a general model for the dynamic behavior of multiphase
      systems in which the bulk phases and interfaces have a complex microstructure
      (for example, immiscible polymer blends with added compatibilizers, or polymer
      stabilized emulsions with thickening agents dispersed in the continuous phase).
      The model is developed in the context of the GENERIC framework (general equation
      for the nonequilibrium reversible irreversible coupling). We incorporate scalar
      and tensorial structural variables in the set of independent bulk and surface
      excess variables, and these structural variables allow us to link the highly
      nonlinear rheological response typically observed in complex multiphase systems,
      directly to the time evolution of the microstructure of the bulk phases and phase
      interfaces. We present a general form of the Poisson and dissipative brackets for
      the chosen set of bulk and surface excess variables, and show that to satisfy the
      entropy degeneracy property, we need to add several contributions to the moving
      interface normal transfer term, involving the tensorial bulk and interfacial
      structural variables. We present the full set of balance equations, constitutive
      equations, and boundary conditions for the calculation of the time evolution of
      the bulk and interfacial variables, and this general set of equations can be used
      to develop specific models for a wide range of complex multiphase systems. 

PMID- 24032817
TI  - Dynamics of multiphase systems with complex microstructure. II. Particle
      stabilized interfaces.
AB  - In this paper we use the GENERIC (general equation for nonequilibrium reversible
      irreversible coupling) nonequilibrium thermodynamics framework to derive
      constitutive equations for the surface extra stress tensor of an interface
      stabilized by a two-dimensional suspension of anisotropic colloidal particles.
      The dependence of the surface stress tensor on the microstructure of the
      interface is incorporated through a dependence on a single tensorial structural
      variable, characterizing the average orientation of the particles. The
      constitutive equation for the stress tensor is combined with a time-evolution
      equation describing the changes in the orientation tensor as a result of the
      applied deformation field. We examine the predictions of the model in in-plane
      steady shear flow, in-plane oscillatory shear flow, and oscillatory dilatational
      flow. The model is able to predict the experimentally observed shear thinning
      behavior in surface shear flow, and also the experimentally observed emergence of
      even harmonics in the frequency spectrum of the surface stress in oscillatory
      dilatational flow. Our results show that the highly nonlinear stress-deformation
      behavior of interfaces with a complex microstructure can be modeled well using
      simple structural models like the one presented here. 

PMID- 24032818
TI  - Brownian motion of a harmonic oscillator in a noninertial reference frame.
AB  - The Brownian motion of a charged harmonic oscillator in the presence of
      additional force fields, such as a constant magnetic field and arbitrary time
      dependent electric and mechanical forces, is studied in a rotational reference
      frame under uniform motion. By assuming an isotropic surrounding medium (a scalar
      friction constant), we solve explicitly the Smoluchowski equation associated with
      the Langevin equation for the charged harmonic oscillator and calculate the mean
      square displacements along and orthogonal to the rotation axis. 

PMID- 24032819
TI  - Opinion dynamics model with weighted influence: exit probability and dynamics.
AB  - We introduce a stochastic model of binary opinion dynamics in which the opinions
      are determined by the size of the neighboring domains. The exit probability here
      shows a step function behavior, indicating the existence of a separatrix
      distinguishing two different regions of basin of attraction. This behavior, in
      one dimension, is in contrast to other well known opinion dynamics models where
      no such behavior has been observed so far. The coarsening study of the model also
      yields novel exponent values. A lower value of persistence exponent is obtained
      in the present model, which involves stochastic dynamics, when compared to that
      in a similar type of model with deterministic dynamics. This apparently
      counterintuitive result is justified using further analysis. Based on these
      results, it is concluded that the proposed model belongs to a unique dynamical
      class. 

PMID- 24032820
TI  - Group superballistic diffusion: bimodal velocity inducing coexistence of two
      states in a corrugated plane.
AB  - We consider anomalous diffusion of a particle moving in a tilted periodic
      potential in the presence of Levy noise and nonlinear friction. Using Monte Carlo
      simulations, we have found some interesting characteristics of diffusion in such
      a nonlinear system: when the noise intensity is weak and the external force is
      close to the critical value at which local minima of the potential just vanish,
      the nonmonotonic behavior of the effective diffusion index and the superballistic
      diffusion are observed. This is due to the bimodal nature of the velocity
      distribution, and thus the test particles exist in either a running state or a
      long-tailed behind state in the spatial coordinate; the latter is disintegrated
      into small pieces of the probability peaks. We provide a relation between the
      group diffusion coefficient and the phase diffusion coefficient. It is shown that
      the distance between the above two-state centers increasing with time plays the
      definitive role in the superballistic group diffusion. 

PMID- 24032821
TI  - Fractional fluctuation effects on the light scattered by a viscoelastic
      suspension.
AB  - We generalize fluctuating hydrodynamics to study the effect of fractional time
      derivatives on the light-scattering spectrum of a suspension in a viscoelastic
      solvent under an external density gradient. Viscoelasticity introduces additional
      memory effects into the fluctuating hydrodynamic equations, causing the time
      scales associated with the mesoscopic variables and those of the microscopic
      events to be no longer well separated. This situation is taken into account by
      introducing Caputo's fractional time derivative into the description. The
      structure factor of the suspension is calculated, and we find that its
      nonequilibrium correction is an odd function of the frequency. It exhibits a
      shift towards negative frequencies proportional to the magnitude of the imposed
      gradient. We consider solvents that are described by Maxwell's or power-law
      rheological equations of state. The fractional structure factor is compared with
      the nonfractional one, and it is found that the ratio of the former to the latter
      may be positive and up to two orders of magnitude for both types of
      viscoelasticity. This prediction of our model calculation suggests that this
      relative change might be measurable. 

PMID- 24032822
TI  - Intrinsic creep of a granular column subjected to temperature changes.
AB  - Minute external perturbations, such as temperature variations, can lead to a
      creep of the fragile structures that are the granular piles. We report a study,
      resolved in space and time, of the dynamics associated with the slow compaction
      of a granular column submitted to thermal cycles. Avoiding the thermal dilations
      of the container, we observe that the material still creeps, even in the absence
      of external mechanical perturbations. The latter intrinsic creep of the material
      exhibits several surprising features: the compaction of the material is not
      homogeneous along the column height, and sudden collapses involve the entire
      system even if one could expect arches to screen the mechanical interaction
      between regions far apart from one another. In addition, the analysis of the
      dependence of the flow rate on the frequency of the temperature cycles suggests
      that the creep is mainly induced by the propagation of the temperature profile,
      slow temperature changes being less efficient than rapid ones in making the
      material flow. 

PMID- 24032823
TI  - Long-range interactions in randomly driven granular fluids.
AB  - We study the long-range spatial correlations in the nonequilibrium steady state
      of a randomly driven granular fluid with the emphasis on obtaining the explicit
      form of the static structure factors. The presence of immobile particles immersed
      in such a fluidized bed of fine particles leads to the confinement of the
      fluctuation spectrum of the hydrodynamic fields, which results in effective long
      range interactions between the intruders. The analytical predictions are in
      agreement with the results of discrete element method simulations. By changing
      the shape and orientation of the intruders, we address how the effective force is
      affected by small changes in the boundary conditions. 

PMID- 24032824
TI  - Low-velocity impact cratering experiments in a wet sand target.
AB  - Low-velocity impact cratering experiments were conducted in a wet sand target.
      With the addition of interstitial water, the sand stiffens and the yield stress
      sigma(y) increases by a factor of 10 and we observe a significant change in the
      resulting crater shape. A small water saturation (S~0.02) is sufficient to
      inhibit the crater wall collapse, which causes the crater diameter d to decrease
      and the crater depth to increase, and results in the steepening of the crater
      wall. With a further addition of water (S~0.04), the collapse is completely
      inhibited such that cylindrical craters form and the impactor penetration depth
      delta and ejecta dispersal are suppressed. However, for S>0.7, the wet sand
      becomes fluidized such that both d and delta increase thereafter. Comparing the
      relevant stresses, we find that cylindrical craters form when the yield stress is
      more than about three times larger than the gravitational stress such that it can
      withstand collapse. Experiments with different impactor sizes D and velocities
      indicate that for S<=0.02, gravity-regime scaling applies for d. However, the
      scaling gradually fails as S increases. In contrast, we find that delta/D can be
      scaled by the inertial stress normalized by the yield stress, for a wide range of
      S. This difference in the scaling is interpreted as arising from d being affected
      by whether or not the crater wall collapses, whereas delta is determined by the
      penetration process that occurs prior to collapse. The experimental parameter
      space in terms of dimensionless numbers indicates that our experiments may
      correspond to impact cratering in small asteroids.

PMID- 24032825
TI  - Local stresses in the Janssen granular column.
AB  - We study experimentally the distribution of local stresses in a granular material
      confined inside a vertical cylinder. We use an image correlation technique to
      measure the displacement field of the container induced by the forces exerted by
      the grains on the inner wall. We describe an optimization procedure based on the
      linear theory of elastic shells to deduce the distribution of these forces from
      the measured displacement field. They correspond to the stress field of the
      granular material close to the container's inner wall. We first confirm the
      validity of Janssen's description for various experiments, including the
      influence of the bead diameter and the effect of an additional mass on top of the
      granular column. We then apply this method to determine the stress field during
      the gravity-driven discharge of a silo through an aperture. 

PMID- 24032826
TI  - Disordered strictly jammed binary sphere packings attain an anomalously large
      range of densities.
AB  - Previous attempts to simulate disordered binary sphere packings have been limited
      in producing mechanically stable, isostatic packings across a broad spectrum of
      packing fractions. Here we report that disordered strictly jammed binary packings
      (packings that remain mechanically stable under general shear deformations and
      compressions) can be produced with an anomalously large range of average packing
      fractions 0.634<=phi<=0.829 for small to large sphere radius ratios alpha
      restricted to alpha>=0.100. Surprisingly, this range of average packing fractions
      is obtained for packings containing a subset of spheres (called the backbone)
      that are exactly strictly jammed, exactly isostatic, and also generated from
      random initial conditions. Additionally, the average packing fractions of these
      packings at certain alpha and small sphere relative number concentrations x
      approach those of the corresponding densest known ordered packings. These
      findings suggest for entropic reasons that these high-density disordered packings
      should be good glass formers and that they may be easy to prepare experimentally.
      We also identify an unusual feature of the packing fraction of jammed backbones
      (packings with rattlers excluded). The backbone packing fraction is about 0.624
      over the majority of the alpha-x plane, even when large numbers of small spheres
      are present in the backbone. Over the (relatively small) area of the alpha-x
      plane where the backbone is not roughly constant, we find that backbone packing
      fractions range from about 0.606 to 0.829, with the volume of rattler spheres
      comprising between 1.6% and 26.9% of total sphere volume. To generate isostatic
      strictly jammed packings, we use an implementation of the Torquato-Jiao
      sequential linear programming algorithm [Phys. Rev. E 82, 061302 (2010)], which
      is an efficient producer of inherent structures (mechanically stable
      configurations at the local maxima in the density landscape). The identification
      and explicit construction of binary packings with such high packing fractions
      could have important practical implications for granular composites where density
      is critical both to material properties and fabrication cost, including for solid
      propellants, concrete, and ceramics. The densities and structures of jammed
      binary packings at various alpha and x are also relevant to the formation of a
      glass phase in multicomponent metallic systems.

PMID- 24032827
TI  - Stable and metastable hard-sphere crystals in fundamental measure theory.
AB  - Using fully minimized fundamental measure functionals, we investigate free
      energies, vacancy concentrations, and density distributions for bcc, fcc, and hcp
      hard-sphere crystals. Results are complemented by an approach due to Stillinger,
      which is based on expanding the crystal partition function in terms of the number
      n of free particles while the remaining particles are frozen at their ideal
      lattice positions. The free energies of fcc and hcp and one branch of bcc agree
      well with Stillinger's approach truncated at n=2. A second branch of bcc
      solutions features rather spread-out density distributions around lattice sites
      and large equilibrium vacancy concentrations and is presumably linked to the
      shear instability of the bcc phase. Within fundamental measure theory and the
      Stillinger approach (n=2), hcp is more stable than fcc by a free energy per
      particle of about 0.001k(B)T. In previous simulation work, the reverse situation
      has been found, which can be rationalized in terms of effects due to a correlated
      motion of at least five particles in the Stillinger picture.

PMID- 24032828
TI  - Lattice-gas Poisson-Boltzmann approach for sterically asymmetric electrolytes.
AB  - We derive a modification of the Poisson-Boltzmann (PB) equation brought about by
      the finite and different sizes of mobile ions. The equation we obtain contains
      explicitly the size asymmetry of the electrolyte, enabling one to apply the PB
      approach to the cases where this effect may be of importance. We show that the
      modification we propose predicts the asymmetry of the double-layer capacitance.
      Our approach thus provides a transparent analytical framework for a previously
      proposed heuristic modification of the PB equation, which also predicts the same
      effect. In addition, a detailed exposition of the lattice-based calculation of
      the entropy, accounting for steric, spatial correlations, enables us to clearly
      pinpoint some of the drawbacks of such an approach, which are not entirely
      obvious in previous attempts to include the steric effects in the PB equation. 

PMID- 24032829
TI  - Duration of bubble rearrangements in a coarsening foam probed by time-resolved
      diffusing-wave spectroscopy: impact of interfacial rigidity.
AB  - In aqueous foams, the diffusive gas transfer among neighboring bubbles drives a
      coarsening process which is accompanied by intermittent rearrangements of the
      structure. Using time-resolved diffusing-wave spectroscopy, we probe the dynamics
      of these events as a function of the rigidity of the gas-liquid interfaces,
      liquid viscosity, bubble size, and confinement pressure. We present in detail two
      independent techniques for analyzing the light scattering data, from which we
      extract the rearrangement duration. Our results show that interfacial rheology
      has a major impact on this duration. In the case of low interfacial rigidity, the
      rearrangements strongly slow down as the pressure is decreased close to the value
      zero where the bubble packing unjams. In contrast, if the interfaces are rigid,
      rearrangement durations are independent of the confinement pressure in the same
      investigated range. Using scaling arguments, we discuss dissipation mechanisms
      that may explain the observed dependency of the rearrangement dynamics on foam
      structure, pressure, and physicochemical solution properties. 

PMID- 24032830
TI  - Kinetics of DNA-coated sticky particles.
AB  - DNA-functionalized particles are promising for complex self-assembly due to their
      specific controllable thermoreversible interactions. However, there has been
      little work on the kinetics and the aggregation rate, which depend on the rate of
      particle encounters and the probability that an encounter results in particles
      sticking. In this study, we investigate theoretically and experimentally the
      aggregation times of micron-scale particles as a function of DNA coverage and
      salt concentration. Our 2-MUm colloids accommodate up to 70,000 DNA strands. For
      full coverage and high salt concentration, the aggregation time is 5 min while
      for 0.1 coverage and low salt it is 4 days. A simple model using reaction-limited
      kinetics and experimental oligomer hybridization rates describes the data well. A
      controlling factor is the Coulomb barrier at the nanometer scale retarding DNA
      hybridization. Our model allows easy measurements of microscopic hybridization
      rates from macroscopic aggregation and enables the design of complex self
      assembly schemes with controlled kinetics.

PMID- 24032831
TI  - Free-energy functionals of the electrostatic potential for Poisson-Boltzmann
      theory.
AB  - In simulating charged systems, it is often useful to treat some ionic components
      of the system at the mean-field level and solve the Poisson-Boltzmann (PB)
      equation to get their respective density profiles. The numerically intensive task
      of solving the PB equation at each step of the simulation can be bypassed using
      variational methods that treat the electrostatic potential as a dynamic variable.
      But such approaches require the access to a true free-energy functional: a
      functional that not only provides the correct solution of the PB equation upon
      extremization, but also evaluates to the true free energy of the system at its
      minimum. Moreover, the numerical efficiency of such procedures is further
      enhanced if the free-energy functional is local and is expressed in terms of the
      electrostatic potential. Existing PB functionals of the electrostatic potential,
      while possessing the local structure, are not free-energy functionals. We present
      a variational formulation with a local free-energy functional of the potential.
      In addition, we also construct a nonlocal free-energy functional of the
      electrostatic potential. These functionals are suited for employment in
      simulation schemes based on the ideas of dynamical optimization. 

PMID- 24032832
TI  - Effective electrostatic interactions in mixtures of charged colloids.
AB  - We present a theory of effective electrostatic interactions in polydisperse
      suspensions of charged macroions, generalizing to mixtures a theory previously
      developed for monodisperse suspensions. Combining linear response theory with a
      random phase approximation for microion correlations, we coarse grain the
      microion degrees of freedom to derive general expressions for effective macroion
      macroion pair potentials and a one-body volume energy. For model mixtures of
      charged hard-sphere colloids, we give explicit analytical expressions. The
      resulting effective pair potentials have the same general form as predicted by
      linearized Poisson-Boltzmann theory, but consistently incorporate dependence on
      macroion density and excluded volume via the Debye screening constant. The volume
      energy, which depends on the average macroion density, contributes to the free
      energy and so can influence thermodynamic properties of deionized suspensions. To
      validate the theory, we compute radial distribution functions of binary mixtures
      of oppositely charged colloidal macroions from molecular dynamics simulations of
      the coarse-grained model (with implicit microions), taking effective pair
      potentials as input. Our results agree closely with corresponding results from
      more computationally intensive Monte Carlo simulations of the primitive model
      (with explicit microions). Simulations of a mixture with large size and charge
      asymmetries indicate that charged nanoparticles can enhance electrostatic
      screening of charged colloids. The theory presented here lays a foundation for
      future large-scale modeling of complex mixtures of charged colloids,
      nanoparticles, and polyelectrolytes. 

PMID- 24032833
TI  - Orientational ordering of colloidal dispersions by application of time-dependent
      external forces.
AB  - We discuss a method of organizing incoherent motion of a colloidal suspension to
      produce synchronized, coherent motion, extending the discussion of our recent
      Letter [Moths and Witten, Phys. Rev. Lett. 110, 028301 (2013)]. The method does
      not require interaction between the objects. Instead, the effect is controlled by
      the "twist matrix" which gives the angular velocity of an asymmetric object in a
      fluid resulting from a weak external force. We analyze the two types of forcing
      considered in the Letter: a force alternating between two directions and a
      continuously rotating force. For the alternating force, we justify the claim of
      the Letter that under appropriate forcing conditions, the orientational entropy
      of the objects decreases indefinitely with time, on average. We provide a bound
      on that rate in terms of the twist matrix. For the case of rotating force, we
      derive conditions for phased-locked motion of the objects to the force and prove
      that there is only one stable phase-locked orientation under these conditions. We
      find numerically that the fastest alignment typically occurs for tilt angles of
      order unity. We discuss how the alignment effect scales with the object size for
      external forcing caused by gravity or an electric field. Under practical forcing
      conditions we estimate that the alignment should persist despite rotational
      diffusion for objects larger than about 10 microns. Potential misalignment owing
      to hydrodynamic interaction of the objects is estimated to be negligible at
      volume fractions smaller than about 10(-4.5) (10(-3)) when the forcing is
      gravitational (electrophoretic).

PMID- 24032834
TI  - Fluctuating mobility generation and transport in glasses.
AB  - In the context of the random first order transition theory we use an extended
      mode coupling theory of the glass transition that includes activated events to
      account for spatiotemporal structures in rejuvenating glasses. We numerically
      solve fluctuating dynamical equations for mobility and fictive temperature fields
      which capture both mobility generation through activated events and facilitation
      effects. Upon rejuvenating, a source of high mobility at a glass surface
      initiates a growth front of mobility which propagates into the unstable low
      mobility region. The speed of the front quantitatively agrees with experiments on
      the rejuvenation of ultrastable glasses, which "melt" from their surface. 

PMID- 24032835
TI  - Attractive interaction and bridging transition between neutral colloidal
      particles due to preferential adsorption in a near-critical binary mixture.
AB  - We examine the solvent-mediated interaction between two neutral colloidal
      particles due to preferential adsorption in a near-critical binary mixture. We
      take into account the renormalization effect due to the critical fluctuations
      using the recent local functional theory [J. Chem. Phys. 136, 114704 (2012)]. We
      calculate the free energy and the force between two colloidal particles as
      functions of the temperature T, the composition far from the colloidal particles
      c(infinity), and the colloid separation l. The interaction is much enhanced when
      the component favored by the colloid surfaces is poor in the reservoir. For such
      off-critical compositions, we find a surface of a first-order bridging transition
      l=l(cx)(T,c(infinity)) in the T-c(infinity)-l space in a universal, scaled form,
      across which a discontinuous change occurs between separated and bridged states.
      This surface starts from the bulk coexistence surface (CX) and ends at a bridging
      critical line where l is determined by T as l=l(c)(T). On approaching the
      critical line, the discontinuity vanishes and the derivatives of the force with
      respect to T and l both diverge. Furthermore, bridged states continuously change
      into separated states if c(infinity) (or T) is varied from a value on CX to a
      value far from CX with l kept smaller than l(c)(T).

PMID- 24032836
TI  - Yield-strain and shear-band direction in amorphous solids under two-dimensional
      uniaxial loading.
AB  - It is well known experimentally that well-quenched amorphous solids exhibit a
      plastic instability in the form of a catastrophic shear localization at a well
      defined value of the external strain. The instability may develop to a shear band
      that in some cases is followed by a fracture. It is also known that the values of
      the yield strain (and yield stress), as well as the direction of the shear band
      with respect to the principal stress axis, vary considerably with variations in
      the external loading conditions. In this paper we present a microscopic theory of
      these phenomena for two-dimensional athermal amorphous solids that are strained
      quasistatically. We present analytic formulas for the yield strains for different
      loading conditions, as well as for the angles of the shear bands. We explain that
      the external loading conditions determine the eigenvalues of the quadrupolar
      Eshelby inclusions which model the nonaffine displacement field. These inclusions
      model elementary plastic events and determine both the yield strain and the
      direction of the shear band. We show that the angles of the shear bands with
      respect to the principal stress axis are limited theoretically between 30 degrees
      and 60 degrees . Available experimental data conform to this prediction.

PMID- 24032837
TI  - Capturing self-propelled particles in a moving microwedge.
AB  - Catching fish with a fishing net is typically done either by dragging a fishing
      net through quiescent water or by placing a stationary basket trap into a stream.
      We transfer these general concepts to micron-sized self-motile particles moving
      in a solvent at low Reynolds number and study their collective trapping behavior
      by means of computer simulations of a two-dimensional system of self-propelled
      rods. A chevron-shaped obstacle is dragged through the active suspension with a
      constant speed v and acts as a trapping "net." Three trapping states can be
      identified corresponding to no trapping, partial trapping, and complete trapping
      and their relative stability is studied as a function of the apex angle of the
      wedge, the swimmer density, and the drag speed v. When the net is dragged along
      the inner wedge, complete trapping is facilitated and a partially trapped state
      changes into a complete trapping state if the drag speed exceeds a certain value.
      Reversing the drag direction leads to a reentrant transition from no trapping to
      complete trapping and then back to no trapping upon increasing the drag speed
      along the outer wedge contour. The transition to complete trapping is marked by a
      templated self-assembly of rods forming polar smectic structures anchored onto
      the inner contour of the wedge. Our predictions can be verified in experiments of
      artificial or microbial swimmers confined in microfluidic trapping devices. 

PMID- 24032838
TI  - Overlap fluctuations in glass-forming liquids.
AB  - We analyze numerically thermal fluctuations of the static overlap between
      equilibrium configurations in a glass-forming liquid approaching the glass
      transition. We find that the emergence of slow dynamics near the onset
      temperature correlates with the development of non-Gaussian probability
      distributions of overlap fluctuations, measured using both annealed and quenched
      definitions. Below a critical temperature, a thermodynamic field conjugate to the
      overlap induces a first-order phase transition, whose existence we numerically
      demonstrate in the annealed case. These results establish that the approach to
      the glass transition is accompanied by profound changes in the nature of
      thermodynamic fluctuations, deconstructing the view that glassy dynamics occurs
      with little structural evolution. 

PMID- 24032839
TI  - Distribution of local relaxation events in an aging three-dimensional glass:
      spatiotemporal correlation and dynamical heterogeneity.
AB  - We investigate the spatiotemporal distribution of microscopic relaxation events,
      defined through particle hops, in a model polymer glass using molecular dynamics
      simulations. We introduce an efficient algorithm to directly identify hops during
      the simulation, which allows the creation of a map of relaxation events for the
      whole system. Based on this map, we present density-density correlations between
      hops and directly extract correlation scales. These scales define collaboratively
      rearranging groups of particles and their size distributions are presented as a
      function of temperature and age. Dynamical heterogeneity is spatially resolved as
      the aggregation of hops into clusters, and we analyze their volume distribution
      and growth during aging. A direct comparison with the four-point dynamical
      susceptibility chi(4) reveals the formation of a single dominating cluster prior
      to the chi(4) peak, which indicates maximally correlated dynamics. An analysis of
      the fractal dimension of the hop clusters finds slightly noncompact shapes in
      excellent agreement with independent estimates from four-point correlations.

PMID- 24032840
TI  - Phonons in two-dimensional soft colloidal crystals.
AB  - The vibrational modes of pristine and polycrystalline monolayer colloidal
      crystals composed of thermosensitive microgel particles are measured using video
      microscopy and covariance matrix analysis. At low frequencies, the Debye relation
      for two-dimensional harmonic crystals is observed in both crystal types; at
      higher frequencies, evidence for van Hove singularities in the phonon density of
      states is significantly smeared out by experimental noise and measurement
      statistics. The effects of these errors are analyzed using numerical simulations.
      We introduce methods to correct for these limitations, which can be applied to
      disordered systems as well as crystalline ones, and we show that application of
      the error correction procedure to the experimental data leads to more pronounced
      van Hove singularities in the pristine crystal. Finally, quasilocalized low
      frequency modes in polycrystalline two-dimensional colloidal crystals are
      identified and demonstrated to correlate with structural defects such as
      dislocations, suggesting that quasilocalized low-frequency phonon modes may be
      used to identify local regions vulnerable to rearrangements in crystalline as
      well as amorphous solids. 

PMID- 24032841
TI  - Dynamics of nanoconfined water under pressure.
AB  - We report a study of the effects of pressure on the diffusivity of water
      molecules confined in single-wall carbon nanotubes (SWNT) with average mean pore
      diameter of ~16 A. The measurements were carried out using high-resolution
      neutron scattering, over the temperature range 220<=T<=260 K, and at two pressure
      conditions: ambient and elevated pressure. The high pressure data were collected
      at constant volume on cooling, with P varying from ~1.92 kbar at temperature
      T=260 K to ~1.85 kbar at T=220 K. Analysis of the observed dynamic structure
      factor S(Q,E) reveals the presence of two relaxation processes, a faster
      diffusion component (FC) associated with the motion of "caged" or restricted
      molecules, and a slower component arising from the free water molecules diffusing
      within the SWNT matrix. While the temperature dependence of the slow relaxation
      time exhibits a Vogel-Fulcher-Tammann law and is non-Arrhenius in nature, the
      faster component follows an Arrhenius exponential law at both pressure
      conditions. The application of pressure remarkably slows down the overall
      molecular dynamics, in agreement with previous observations, but most notably
      affects the slow relaxation. The faster relaxation shows marginal or no change
      with pressure within the experimental conditions.

PMID- 24032842
TI  - Translational and rotational dynamics of colloidal particles in suspension:
      effect of shear.
AB  - We report a generalization of a nonequilibrium thermodynamic theory for the
      mesoscopic dynamics of radially symmetric interacting particles to anisotropic
      pairwise interactions and attain the one- and two-particle Fokker-Planck kinetics
      equations at a low-density limit that provides the translational-rotational
      coupling of their motion due to hydrodynamic interactions, from which we derived
      the balance equations of linear, angular momentum, and energy dissipation due to
      particle interactions and energy interchange with heat bath. In this low-density
      approximation, an already-known virial expression for the long-time translational
      collective diffusion coefficient of an orientational isotropic suspension in
      terms of the fluid equilibrium microstructure is recovered. An external shear
      flow induces, in the diffusive regime, vorticity effects into the rotational
      diffusion property of the colloidal particles. They manifest in the appearance of
      the particle's rotational viscosity due to vortex flow. The Smoluchowski equation
      that governs the dynamical relaxation of colloid microstructure due to particle's
      Brownian motion under stationary flow is provided. 

PMID- 24032843
TI  - Microbranching in mode-I fracture in a randomly perturbed lattice.
AB  - We study mode-I fracture in lattices using atomistic simulations with randomly
      distributed bond lengths. By using a small parameter that measures the variation
      of the bond length between the atoms in perfect lattices and using a three-body
      force law, simulations reproduce the qualitative behavior of the beyond-steady
      state cracks in the high-velocity regime, including reasonable microbranching. In
      particular, the effect of the lattice structure on the crack appears minimal,
      even though in terms of the physical properties such as the structure factor g(r)
      and the radial or angular distributions, these lattices share the physical
      properties of perfect lattices rather than those of an amorphous material (e.g.,
      the continuous random network model). A clear transition can be seen between
      steady-state cracks, where a single crack propagates in the midline of the
      sample, and the regime of unstable cracks, where microbranches start to appear
      near the main crack, in line with previous experimental results. This is seen in
      both a honeycomb lattice and a fully hexagonal lattice. This model reproduces the
      main physical features of propagating cracks in brittle materials, including the
      total length of microbranches as a function of driving displacement and the
      increasing amplitude of oscillations of the electrical resistance. In addition,
      preliminary indications of power-law behavior of the microbranch shapes can be
      seen, potentially reproducing one of the most intriguing experimental results of
      brittle fracture. There was found to exist a critical degree of disorder, i.e., a
      sharp threshold between the cleaving behavior characterizing perfect lattices and
      the microbranching behavior that characterizes amorphous materials. 

PMID- 24032844
TI  - Long-wave model for strongly anisotropic growth of a crystal step.
AB  - A continuum model for the dynamics of a single step with the strongly anisotropic
      line energy is formulated and analyzed. The step grows by attachment of adatoms
      from the lower terrace, onto which atoms adsorb from a vapor phase or from a
      molecular beam, and the desorption is nonnegligible (the "one-sided" model). Via
      a multiscale expansion, we derived a long-wave, strongly nonlinear, and strongly
      anisotropic evolution PDE for the step profile. Written in terms of the step
      slope, the PDE can be represented in a form similar to a convective Cahn-Hilliard
      equation. We performed the linear stability analysis and computed the nonlinear
      dynamics. Linear stability depends on whether the stiffness is minimum or maximum
      in the direction of the step growth. It also depends nontrivially on the
      combination of the anisotropy strength parameter and the atomic flux from the
      terrace to the step. Computations show formation and coarsening of a hill-and
      valley structure superimposed onto a long-wavelength profile, which independently
      coarsens. Coarsening laws for the hill-and-valley structure are computed for two
      principal orientations of a maximum step stiffness, the increasing anisotropy
      strength, and the varying atomic flux. 

PMID- 24032845
TI  - Desorption-induced structural changes of metal/Si(111) surfaces: kinetic Monte
      Carlo simulations.
AB  - We used a configuration-based kinetic Monte Carlo model to explain important
      features related to formation of the (?3*?3)R30 degrees  mosaic of metal and
      semiconductor atoms on the Si(111) surface. Using first-order desorption
      processes, we simulate the surprising zero-order desorption spectra, reported in
      some cases of metal desorption from the Si(111) surface. We show that the
      mechanism responsible for the zerolike order of desorption is the enhanced
      desorption from disordered areas. Formation of the ?3*?3 mosaic with properties
      of a strongly frustrated antiferromagnetic Ising model is simulated by a
      configuration-sensitive desorption. For substitution of desorbed metal atoms by
      Si adatoms, fast diffusion of the adatoms on top of a 1*1 layer is proposed as
      the most probable. Simulations of desorption-induced structural transitions
      provide us a link between underlying atomistic processes and the observed
      evolving morphologies with resultant macroscopic desorption fluxes. An effect of
      the desorption sensitivity on a configuration of neighboring atoms is emphasized.

PMID- 24032846
TI  - Linear stability analysis of a horizontal phase boundary separating two miscible
      liquids.
AB  - The evolution of small disturbances to a horizontal interface separating two
      miscible liquids is examined. The aim is to investigate how the interfacial mass
      transfer affects development of the Rayleigh-Taylor instability and propagation
      and damping of the gravity-capillary waves. The phase-field approach is employed
      to model the evolution of a miscible multiphase system. Within this approach, the
      interface is represented as a transitional layer of small but nonzero thickness.
      The thermodynamics is defined by the Landau free energy function. Initially, the
      liquid-liquid binary system is assumed to be out of its thermodynamic
      equilibrium, and hence, the system undergoes a slow transition to its
      thermodynamic equilibrium. The linear stability of such a slowly diffusing
      interface with respect to normal hydro- and thermodynamic perturbations is
      numerically studied. As a result, we show that the eigenvalue spectra for a sharp
      immiscible interface can be successfully reproduced for long-wave disturbances,
      with wavelengths exceeding the interface thickness. We also find that thin
      interfaces are thermodynamically stable, while thicker interfaces, with the
      thicknesses exceeding an equilibrium value, are thermodynamically unstable. The
      thermodynamic instability can make the configuration with a heavier liquid lying
      underneath unstable. We also find that the interfacial mass transfer introduces
      additional dissipation, reducing the growth rate of the Rayleigh-Taylor
      instability and increasing the dissipation of the gravity waves. Moreover, mutual
      action of diffusive and viscous effects completely suppresses development of the
      modes with shorter wavelengths. 

PMID- 24032847
TI  - Anomalously fast kinetics of lipid monolayer buckling.
AB  - We reexamine previous observations of folding kinetics of compressed lipid
      monolayers in light of the accepted mechanical buckling mechanism recently
      proposed by L. Pocivavsek et al. [Science 320, 912 (2008)]. Using simple models,
      we set conservative limits on (a) the energy released in the mechanical buckling
      process and (b) the kinetic energy entailed by the observed folding motion. These
      limits imply a kinetic energy at least 30 times greater than the energy supplied
      by the buckling instability. We discuss possible extensions of the accepted
      picture that might resolve this discrepancy. 

PMID- 24032848
TI  - Interface kinetics in phase-field models: isothermal transformations in binary
      alloys and step dynamics in molecular-beam epitaxy.
AB  - We present a unified description of interface kinetic effects in phase-field
      models for isothermal transformations in binary alloys and steps dynamics in
      molecular-beam-epitaxy. The phase-field equations of motion incorporate a kinetic
      cross-coupling between the phase field and the concentration field. This cross
      coupling generalizes the phenomenology of kinetic effects and was omitted until
      recently in classical phase-field models. We derive general expressions
      (independent of the details of the phase-field model) for the kinetic
      coefficients within the corresponding macroscopic approach using a physically
      motivated reduction procedure. The latter is equivalent to the so-called thin
      interface limit but is technically simpler. It involves the calculation of the
      effective dissipation that can be ascribed to the interface in the phase-field
      model. We discuss in detail the possibility of a nonpositive definite matrix of
      kinetic coefficients, i.e., a negative effective interface dissipation, although
      being in the range of stability of the underlying phase-field model. Numerically
      we study the step-bunching instability in molecular-beam-epitaxy due to the
      Ehrlich-Schwoebel effect, present in our model due to the cross-coupling. Using
      the reduction procedure we compare the results of the phase-field simulations
      with the analytical predictions of the macroscopic approach. 

PMID- 24032849
TI  - Anharmonicity, solvation forces, and resolution in atomic force microscopy at the
      solid-liquid interface.
AB  - Solid-liquid interfaces are central to nanoscale science and technology and
      control processes as diverse as self-assembly, heterogeneous catalysis, wetting,
      electrochemistry, or protein function. Experimentally, measuring the structure
      and dynamics of solid-liquid interfaces with molecular resolution remains a
      challenge. This task can, in principle, be achieved with atomic force microscopy
      (AFM), which functions locally, and with nanometer precision. When operated
      dynamically and at small amplitudes, AFM can provide molecular-level images of
      the liquid solvation layers at the interfaces. At larger amplitudes, results in
      the field of multifrequency AFM have shown that anharmonicities in the tip motion
      can provide quantitative information about the solid's mechanical properties. The
      two approaches probe opposite aspects of the interface and are generally seen as
      distinct. Here it is shown that, for amplitudes A<d, the thickness of the
      solvation region, the tip mainly probes the interfacial liquid, and subnanometer
      resolution can be achieved through solvation forces. For A>d, the tip trajectory
      becomes rapidly anharmonic due to the tip tapping the solid, and the resolution
      decreases. A nonlinear transition between the two regimes occurs for A~d and can
      be quantified with the second harmonic of the tip oscillation. These results,
      confirmed by computer simulations, remain valid in most experimental conditions.
      Significantly, they provide an objective criterion to enhance resolution and to
      decide whether the results are dominated by the properties of the solid or of the
      liquid.

PMID- 24032850
TI  - Transitions through critical temperatures in nematic liquid crystals.
AB  - We obtain estimates for critical nematic liquid crystal (LC) temperatures under
      the action of a slowly varying temperature-dependent control variable. We show
      that biaxiality has a negligible effect within our model and that these delay
      estimates are well described by a purely uniaxial model. The static theory
      predicts two critical temperatures: the supercooling temperature below which the
      isotropic phase loses stability and the superheating temperature above which the
      ordered nematic states do not exist. In contrast to the static problem, the
      isotropic phase exhibits a memory effect below the supercooling temperature in
      the dynamic framework. This delayed loss of stability is independent of the rate
      of change of temperature and depends purely on the initial value of the
      temperature. We also show how our results can be used to improve estimates for LC
      material constants. 

PMID- 24032851
TI  - Shape and chirality transitions in off-axis twist nematic elastomer ribbons.
AB  - Using both experiments and finite element simulations, we explore the shape
      evolution of off-axis twist nematic elastomer ribbons as a function of
      temperature. The elastomers are prepared by cross-linking the mesogens with
      planar anchoring of the director at top and bottom surfaces with a 90 degrees 
      left-handed twist. Shape evolution depends sensitively on the off-axis director
      orientation at the sample midplane. Both experiments and theoretical studies show
      that when the director at midplane is parallel to either the ribbon's long or
      short axes, ribbons form either helicoids or spirals depending on aspect ratio
      and temperature. Simulation studies show that if the director at midplane is off
      axis, ribbons never form helicoids, instead evolving to distorted spiral shapes.
      Experimental studies for two samples with off-axis geometry show agreement with
      this prediction. Samples in all these geometries show a remarkable transition
      from right- to left-handed chiral shapes on change of temperature. Simulations
      predict off-axis samples also change their macroscopic chirality at fixed
      temperature, depending on the angular offset. These results provide insight into
      the mechanisms driving shape evolution and macroscopic chirality, enabling
      engineering design of these materials for future applications.

PMID- 24032852
TI  - Chemically induced twist-bend nematic liquid crystals, liquid crystal dimers, and
      negative elastic constants.
AB  - Here we report the chemical induction of the twist-bend nematic phase in a
      nematic mixture of ether-linked liquid crystal dimers by the addition of a dimer
      with methylene links; all dimers have an odd number of groups in the spacer
      connecting the two mesogenic groups. The twist-bend phase has been identified
      from its optical texture and x-ray scattering pattern as well as NMR
      spectroscopy, which demonstrates the phase chirality. Theory predicts that the
      key macroscopic property required for the stability of this chiral phase formed
      from achiral molecules is for the bend elastic constant to tend to be negative;
      in addition the twist elastic constant should be smaller than half the splay
      elastic constant. To test these important aspects of the prediction we have
      measured the bend and splay elastic constants in the nematic phase preceding the
      twist-bend nematic using the classic Frederiks methodology and all three elastic
      constants employing the dynamic light scattering approach. Our results show that,
      unlike the splay, the bend elastic constant is small and decreases significantly
      as the transition to the induced twist-bend nematic phase is approached, but then
      exhibits unexpected behavior prior to the phase transition. 

PMID- 24032853
TI  - Positron annihilation studies of 4-n-butyl-4'-isothiocyanato-1,1'-biphenyl.
AB  - Positron annihilation lifetime spectroscopy (PALS) measurements were performed
      between 93 and 293 K in order to study the supercooled smectic-E (Sm-E) phase of
      4-n-butyl-4'-isothiocyanato-1,1'-biphenyl (4TCB), the ordered molecular crystal
      of 4TCB, and the phase transition between the Sm-E phase and the ordered
      molecular crystal of 4TCB. The phase transition was well reflected in the abrupt
      increase of the ortho-positronium (o-Ps) lifetime and intensity. The value of the
      o-Ps lifetime in the Sm-E liquid crystalline phase of 4TCB, i.e., 2.21 ns at room
      temperature, was explained by the formation of bubbles induced by Ps atoms, which
      are created due to a liquidlike state of the butyl chains of 4TCB molecules in
      the Sm-E phase. The temperature dependence of the o-Ps intensity for the
      supercooled Sm-E phase can be explained by thermal generation of sites where
      bubbles are formed; an activation energy equal to 0.30+/-0.02 eV was estimated.
      This value was compared with the activation energies of molecular motions. The o
      Ps lifetime in the ordered molecular crystal was interpreted as originating from
      the annihilation of o-Ps confined in molecular vacancy-type imperfections in the
      crystal lattice. The value of the o-Ps pickoff annihilation between 1.8 and 1.9
      ns is in accordance with the size of the molecular vacancy for the 4TCB crystal
      lattice. Its intensity is lower than 5%. The isothermal crystallization of the
      4TCB Sm-E phase was observed by PALS. The low-dimensional crystal growth was
      concluded from the Avrami equation fitted to the time dependence of the o-Ps
      intensity, which resulted in an Avrami exponent equal to 1.73.

PMID- 24032854
TI  - Field-induced director dynamics in confined nematic liquid crystals imposed by a
      strong orthogonal electric field.
AB  - The field-induced director dynamics for a low molar mass nematic liquid crystal
      (LC) has been investigated theoretically based on the hydrodynamic theory
      including the director motion with appropriate boundary and initial conditions.
      Analysis of the numerical results for the turn-on process provides evidence for
      the appearance of the spatially periodic patterns in 4-n-pentyl-4'-cyanobiphenyl
      LC film, only in response to the suddenly applied strong electric field
      orthogonal to the magnetic field. It has been shown that at the values of the
      voltage of 200 V across the 194.7 MUm LC film and the magnetic field of 7.05 T
      directed at the angle alpha=1.57(~89.99 degrees ) between two fields, there is a
      threshold value of the amplitude of the thermal fluctuations of the director over
      the LC sample which provides the nonuniform rotation mode rather than the uniform
      one, whereas the lower values both of the amplitude and the angle alpha
      [<1.565(~88.81 degrees )] dominate the uniform mode. During the turn-off process,
      the reorientation of the director to its equilibrium orientation is characterized
      by the complex destruction of the initially periodic structure to a monodomain
      state.

PMID- 24032855
TI  - Dynamic light scattering and viscosity measurements in a ternary and quaternary
      discotic lyotropic nematic liquid crystal: tuning the backflow with salt.
AB  - Using a dynamic light scattering technique, we measure the damping rate of
      thermal fluctuations of the nematic director for the so-called disklike nematic
      N(D) phase of both the ternary lyotropic K-laurate-1-decanol-H(2)O system and the
      quaternary one of similar composition except for the addition of salt
      (K(2)SO(4)). By varying the scattering angle in suitable geometries and
      polarizations, we are able to measure the orientational diffusivities associated
      with the pure deformations of splay and twist. A previous study made in the N(D)
      phase of the same ternary system yielded a large deviation between the splay and
      twist diffusivities. The effect was then interpreted in terms of the anisotropy
      between their associated viscosities due to induced flows, or backflow. In the
      present work we observe a strong increase of the backflow as an effect of the
      added salt. In addition, we make auxiliary measurements of shear viscosity and
      magnetic instabilities, which help to characterize the effect of the salt in the
      orientational diffusivities as they are mixed quantities involving elastic
      constants and viscosity coefficients.

PMID- 24032856
TI  - Deviations of the glass transition temperature in amorphous conjugated polymer
      thin films.
AB  - The deviations of the glass transition temperature (T(g)) in thin films of an
      amorphous conjugated polymer poly(9,9-dioctylfluorene-co-N-(4
      butylphenyl)diphenylamine) (TFB) are reported. Monotonic and nonmonotonic T(g)
      deviations are observed in TFB thin films supported on Si-SiOx and poly(3,4
      ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS), respectively. A three
      layer model is developed to fit both monotonic and nonmonotonic T(g) deviations
      in these films. A 5-nm PEDOT:PSS capping layer was not found to be effective to
      remove the free-surface effect in Si-SiOx supported TFB films.

PMID- 24032857
TI  - Thermomechanical properties and deformation of coarse-grained models of hard-soft
      block copolymers.
AB  - In this paper, we investigate the enhancement mechanism of the mechanical
      properties for hard-soft block copolymers by using molecular dynamics simulations
      at various temperatures. A coarse-grained approach is adopted to study
      sufficiently generic models. Our numerical experiments demonstrate that the
      nonbond potential plays a more significant role in mechanical properties compared
      to the bond potential. This finding serves as a cornerstone to understand the
      hard-soft materials. To explore the effect of hard segments, four copolymers with
      different concentrations and energy factors that describe the interaction between
      hard beads are conducted. Simulation results show that the mechanical
      performances of the system with large attractive force and small concentration of
      hard segments could be improved dramatically in conjunction with a moderate
      increment of the glass transition temperature. In particular, the energy factor
      shows a substantial influence in determining the microphase separation as well as
      the morphology of hard domains. These observations are believed to provide design
      guidelines for polymeric materials in engineering practice. 

PMID- 24032858
TI  - DNA-binding-protein inhomogeneity in E. coli modeled as biphasic facilitated
      diffusion.
AB  - We have recently shown that nonspecifically bound lac repressors are spatially
      inhomogeneous in E. coli cells and depends upon the location of its encoding gene
      and the DNA compaction state [Kuhlman and Cox, Mol. Syst. Biol. 8, 610 (2012)].
      Here we model this inhomogeneity as a consequence of diffusion within and
      exchange between two distinct intracellular phases: the condensed chromosomal DNA
      and an extrachromosomal compartment, the cytoplasm. We discuss the consequences
      of this model for the target search process. 

PMID- 24032859
TI  - Entrainment range of nonidentical circadian oscillators by a light-dark cycle.
AB  - The suprachiasmatic nucleus (SCN) is a principal circadian clock in mammals,
      which controls physiological and behavioral daily rhythms. The SCN has two main
      features: Maintaining a rhythmic cycle of approximately 24 h in the absence of a
      light-dark cycle (free-running period) and the ability to entrain to external
      light-dark cycles. Both free-running period and range of entrainment vary from
      one species to another. To understand this phenomenon, we investigated the
      diversity of a free-running period by the distribution of coupling strengths in
      our previous work [Phys. Rev. E 80, 030904(R) (2009)]. In this paper we
      numerically found that the dispersion of intrinsic periods among SCN neurons
      influence the entrainment range of the SCN, but has little influence on the free
      running periods under constant darkness. This indicates that the dispersion of
      coupling strengths determines the diversity in free-running periods, while the
      dispersion of intrinsic periods determines the diversity in the entrainment
      range. A theoretical analysis based on two coupled neurons is presented to
      explain the results of numerical simulations. 

PMID- 24032860
TI  - Role of directional fidelity in multiple aspects of extreme performance of the
      F(1)-ATPase motor.
AB  - Quantitative understanding of the best possible performance of nanomotors allowed
      by physical laws pertains to the study of nanomotors from biology as well as
      nanotechnology. The biological nanomotor F(1) ATPase is the best available model
      system as it is the only nanomotor known for extreme energy conversion near the
      limit of energy conservation. Using a unified theoretical framework centered on a
      concept called directional fidelity, we analyze recent experiments in which the
      F(1) motor's performance was measured for controlled chemical potentials and
      expose from the experiments quantitative evidence for the motor's multiple
      extreme performances in directional fidelity, speed, and catalytic capability
      close to physical limits. Specifically, the motor nearly exhausts the available
      energy from the fuel to retain the highest possible directional fidelity for an
      arbitrary load, encompassing the motor's extreme energy conversion and beyond.
      The theory-experiment comparison implies a tight chemomechanical coupling up to
      stalemate as futile steps occur, but unlikely involve fuel consumption. The F(1)
      motor data also help clarify the relation between directional fidelity and
      experimentally measured stepping ratio.

PMID- 24032861
TI  - Transition from an antiphase error-correction mode to a synchronization mode in
      mutual hand tracking.
AB  - Proactive motion in hand tracking and in finger bending, in which the body motion
      occurs prior to the reference signal, has been previously reported when a
      periodic target signal was shown to the subjects at relatively high frequencies.
      These phenomena indicate that the human sensory-motor system tends to choose an
      anticipatory mode rather than a reactive mode, when the target motion is
      relatively fast. The present research was undertaken to study what kind of mode
      appears in the sensory-motor system when two persons were asked to track the hand
      position of the partner at various mean tracking frequency. The experimental
      results showed that a transition from a mutual error-correction mode to a
      synchronization mode occurred in the same region of the transition frequency with
      the one from a reactive error-correction mode to a proactive anticipatory mode
      reported previously in the target tracking experiments of the single subjects.
      Present research indicated that synchronization of body motion occurred only when
      both of the pair subjects operated in a proactive anticipatory mode. We also
      presented mathematical models to explain the behavior of the error-correction
      mode and the synchronization mode. 

PMID- 24032862
TI  - Quantifying spatial structure in experimental observations and agent-based
      simulations using pair-correlation functions.
AB  - We define a pair-correlation function that can be used to characterize
      spatiotemporal patterning in experimental images and snapshots from discrete
      simulations. Unlike previous pair-correlation functions, the pair-correlation
      functions developed here depend on the location and size of objects. The pair
      correlation function can be used to indicate complete spatial randomness,
      aggregation, or segregation over a range of length scales, and quantifies spatial
      structures such as the shape, size, and distribution of clusters. Comparing pair
      correlation data for various experimental and simulation images illustrates their
      potential use as a summary statistic for calibrating discrete models of various
      physical processes. 

PMID- 24032863
TI  - Multiplectoneme phase of double-stranded DNA under torsion.
AB  - We use the wormlike chain model to study supercoiling of DNA under tension and
      torque. The model reproduces experimental data for a broad range of forces, salt
      concentrations, and contour lengths. We find a plane of first-order phase
      transitions ending in a smeared-out line of critical points, the multiplectoneme
      phase, which is characterized by a fast twist-mediated diffusion of plectonemes
      and a torque that rises after plectoneme formation with increasing linking
      number. The discovery of this phase at the same time resolves the discrepancies
      between existing models and experiment. 

PMID- 24032864
TI  - Registration and analysis of the shape fluctuations of nearly spherical lipid
      vesicles.
AB  - The analysis of shape fluctuations of giant nearly spherical lipid vesicles
      observed via optical microscopy is one of the widely used methods for the
      determination of the bending elasticity of lipid membranes. Although the method
      has been used already for three decades, the values of this material constant,
      obtained by different groups for membranes of the same composition, in identical
      conditions, differ significantly. The aim of the present work is the development
      of the method, enabling us to avoid the influence of artifacts on the value of
      the measured bending modulus. This is achieved by rejection of some images of the
      vesicle or the whole vesicle when they do not satisfy the requirements (selection
      criteria) of the applied theory. The bending modulus of 1-stearoyl-2-oleoyl-sn
      glycerol-3-phosphocholine lipid membranes is determined via the advanced method
      described here. The results are compared with the values in the literature and
      their difference is discussed. 

PMID- 24032865
TI  - Time-dependent information transmission in a model regulatory circuit.
AB  - Many biological regulatory systems respond with a physiological delay when
      processing signals. A simple model of regulation which respects these features
      shows how the ability of a delayed output to transmit information is limited: at
      short times by the time scale of the dynamic input, at long times by that of the
      dynamic output. We find that topologies of maximally informative networks
      correspond to commonly occurring biological circuits linked to stress response
      and that circuits functioning out of steady state may exploit absorbing states to
      transmit information optimally. 

PMID- 24032866
TI  - Generalized cable theory for neurons in complex and heterogeneous media.
AB  - Cable theory has been developed over the last decade, usually assuming that the
      extracellular space around membranes is a perfect resistor. However,
      extracellular media may display more complex electrical properties due to various
      phenomena, such as polarization, ionic diffusion, or capacitive effects, but
      their impact on cable properties is not known. In this paper, we generalize cable
      theory for membranes embedded in arbitrarily complex extracellular media. We
      outline the generalized cable equations, then consider specific cases. The
      simplest case is a resistive medium, in which case the equations recover the
      traditional cable equations. We show that for more complex media, for example, in
      the presence of ionic diffusion, the impact on cable properties such as voltage
      attenuation can be significant. We illustrate this numerically, always by
      comparing the generalized cable to the traditional cable. We conclude that the
      nature of intracellular and extracellular media may have a strong influence on
      cable filtering as well as on the passive integrative properties of neurons. 

PMID- 24032867
TI  - Exact partition function zeros of the Wako-Saito-Munoz-Eaton beta hairpin model.
AB  - I compute exact partition function zeros of beta hairpins, using both analytic
      and numerical methods, extending previous work [J. Lee, Phys. Rev. Lett. 110,
      248101 (2013)] where only a restricted class of hairpins was considered. The
      zeros of beta hairpins with an odd number of peptide bonds are computed and the
      difference of the distribution of zeros from those for an even number of peptide
      bonds is explained in terms of additional entropy of liberating the extra bond at
      the turn region. Upon the introduction of a hydrophobic core in the central
      region of the hairpin, the zeros are distributed uniformly on two concentric
      circles corresponding to the hydrophobic collapse and the transition to the fully
      folded conformation. One of the circles dissolves as the core moves toward the
      turn or the tip region, which is explained in terms of the similarity of the
      intermediate state with the folded or unfolded states. The exact partition
      function zeros for a hairpin with a more complex structure of native contacts,
      the 16 C-terminal residues of streptococcal protein G B1, are numerically
      computed and their loci are closely approximated by concentric circles. 

PMID- 24032868
TI  - Energetics of the single-headed kinesin KIF1A.
AB  - KIF1A is a single-headed molecular motor that moves processively and
      unidirectionally along a microtubule by using the chemical energy released by
      hydrolyzing adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and
      inorganic phosphate (P(i)). Although the movement of KIF1A seems to have
      successfully been explained by a simple Brownian motor model of the flashing
      ratchet type, this model is not suited to discuss the energetics of KIF1A. We
      introduce an elaborated model of the ratchet type to investigate how the chemical
      free energy is converted into mechanical work by taking account of the binding
      and release of reactant (ATP) and product (ADP and P(i)) molecules to and from
      the motor. The efficiency of energy transduction, the power output, and other
      quantities are calculated from the analytically obtained steady-state solution of
      the Fokker-Planck equations. It turns out that the concentrations of the reactant
      and product molecules that optimize both the efficiency and the power are close
      to those in the cell.

PMID- 24032869
TI  - Protein translocation in narrow pores: inferring bottlenecks from native
      structure topology.
AB  - Coarse-grained simulations of protein translocation across narrow pores suggest
      that the transport is characterized by long stall events. The translocation
      bottlenecks and the associated free-energy barriers are found to be strictly
      related to the structural properties of the protein native structure. The
      ascending ramps of the free-energy profile systematically correspond to regions
      of the chain denser in long range native contacts formed with the untranslocated
      portion of the protein. These very regions are responsible for the stalls
      occurring during the protein transport along the nanopore. The decomposition of
      the free energy in internal energyand entropic terms shows that the dominant
      energetic contribution can be estimated on the base of the protein native
      structure only. Interestingly, the essential features of the dynamics are
      retained in a reduced phenomenological model of the process describing the
      evolution of a suitable collective variable in the associated free-energy
      landscape. 

PMID- 24032870
TI  - Multiscale codes in the nervous system: the problem of noise correlations and the
      ambiguity of periodic scales.
AB  - Encoding information about continuous variables using noisy computational units
      is a challenge; nonetheless, asymptotic theory shows that combining multiple
      periodic scales for coding can be highly precise despite the corrupting influence
      of noise [Mathis, Herz, and Stemmler, Phys. Rev. Lett. 109, 018103 (2012)].
      Indeed, the cortex seems to use periodic, multiscale grid codes to represent
      position accurately. Here we show how such codes can be read out without taking
      the long-term limit; even on short time scales, the precision of such codes
      scales exponentially in the number N of neurons. Does this finding also hold for
      neurons that are not firing in a statistically independent fashion? To assess the
      extent to which biological grid codes are subject to statistical dependences, we
      first analyze the noise correlations between pairs of grid code neurons in
      behaving rodents. We find that if the grids of two neurons align and have the
      same length scale, the noise correlations between the neurons can reach values as
      high as 0.8. For increasing mismatches between the grids of the two neurons, the
      noise correlations fall rapidly. Incorporating such correlations into a
      population coding model reveals that the correlations lessen the resolution, but
      the exponential scaling of resolution with N is unaffected. 

PMID- 24032871
TI  - Transport dynamics of molecular motors that switch between an active and inactive
      state.
AB  - Molecular motors are involved in key transport processes in the cell. Many of
      these motors can switch from an active to a nonactive state, either spontaneously
      or depending on their interaction with other molecules. When active, the motors
      move processively along the filaments, while when inactive they are stationary.
      We treat here the simple case of spontaneously switching motors, between the
      active and inactive states, along an open linear track. We use our recent analogy
      with vehicular traffic, where we go beyond the mean-field description. We map the
      phase diagram of this system, and find that it clearly breaks the symmetry
      between the different phases, as compared to the standard total asymmetric
      exclusion process. We make several predictions that may be testable using
      molecular motors in vitro and in living cells. 

PMID- 24032872
TI  - Mechanism for synchronized motion between two humans in mutual tapping
      experiments: transition from alternative mode to synchronization mode.
AB  - We performed mutual tapping experiments between two humans to investigate the
      conditions required for synchronized motion. A transition from an alternative
      mode to a synchronization mode was discovered under the same conditions as when a
      subject changed from a reactive mode to an anticipation mode in single tapping
      experiments. The experimental results suggest that the cycle time for each
      tapping motion is tuned by a proportional control that is based on
      synchronization errors and cycle time errors. As the tapping frequency increases,
      a mathematical model based on feedback control in the sensory-motor closed loop
      predicts a discrete transition of the mode as the gain factors of the
      proportional control decrease. The conditions for synchronization are shown as a
      consequence of the coupled dynamics based on the next feedback loop in the
      sensory-motor system. 

PMID- 24032873
TI  - Filter-based multiscale entropy analysis of complex physiological time series.
AB  - Multiscale entropy (MSE) has been widely and successfully used in analyzing the
      complexity of physiological time series. We reinterpret the averaging process in
      MSE as filtering a time series by a filter of a piecewise constant type. From
      this viewpoint, we introduce filter-based multiscale entropy (FME), which filters
      a time series to generate multiple frequency components, and then we compute the
      blockwise entropy of the resulting components. By choosing filters adapted to the
      feature of a given time series, FME is able to better capture its multiscale
      information and to provide more flexibility for studying its complexity.
      Motivated by the heart rate turbulence theory, which suggests that the human
      heartbeat interval time series can be described in piecewise linear patterns, we
      propose piecewise linear filter multiscale entropy (PLFME) for the complexity
      analysis of the time series. Numerical results from PLFME are more robust to data
      of various lengths than those from MSE. The numerical performance of the adaptive
      piecewise constant filter multiscale entropy without prior information is
      comparable to that of PLFME, whose design takes prior information into account. 

PMID- 24032874
TI  - Local mechanical response in semiflexible polymer networks subjected to an
      axisymmetric prestress.
AB  - Analytical and numerical calculations are presented for the mechanical response
      of fiber networks in a state of axisymmetric prestress, in the limit where
      geometric nonlinearities such as fiber rotation are negligible. This allows us to
      focus on the anisotropy deriving purely from the nonlinear force-extension curves
      of individual fibers. The number of independent elastic coefficients for
      isotropic, axisymmetric, and fully anisotropic networks are enumerated before
      deriving expressions for the response to a locally applied force that can be
      tested against, e.g., microrheology experiments. Localized forces can generate
      anisotropy away from the point of application, so numerical integration of
      nonlinear continuum equations is employed to determine the stress field, and
      induced mechanical anisotropy, at points located directly behind and in front of
      a force monopole. Results are presented for the wormlike chain model in
      normalized forms, allowing them to be easily mapped to a range of systems.
      Finally, the relevance of these findings to naturally occurring systems and
      directions for future investigation are discussed. 

PMID- 24032875
TI  - Linking actin networks and cell membrane via a reaction-diffusion-elastic
      description of nonlinear filopodia initiation.
AB  - Reaction-diffusion models have been used to describe pattern formation on the
      cellular scale, and traditionally do not include feedback between cellular shape
      changes and biochemical reactions. We introduce here a distinct reaction
      diffusion-elasticity approach: The reaction-diffusion part describes bistability
      between two actin orientations, coupled to the elastic energy of the cell
      membrane deformations. This coupling supports spatially localized patterns, even
      when such solutions do not exist in the uncoupled self-inhibited reaction
      diffusion system. We apply this concept to describe the nonlinear (threshold
      driven) initiation mechanism of actin-based cellular protrusions and provide
      support by several experimental observations. 

PMID- 24032876
TI  - Effect of undulations on spontaneous braid formation.
AB  - This paper is an extension of a recent study where it was shown that forces
      dependent on molecular helical structure may cause two DNA molecules to
      spontaneously braid [R. Cortini et al., Biophys. J. 101, 875 (2011)]. Here,
      bending fluctuations of molecular center lines about the braid axis are
      incorporated into the braiding theory, which may be generalized to other helix
      dependent interactions and other helical molecules. The free energy of the pair
      of molecules is recalculated and compared to its value without incorporating
      undulations. We find that the loss of configurational entropy due to confinement
      of the molecules in the braid is quite high. This contribution to the free energy
      increases the amount of attraction needed for spontaneous braiding due to helix
      dependent forces. The theory will be further developed for plectonemes and braids
      under mechanical forces in later work. 

PMID- 24032877
TI  - Automatic sorting of point pattern sets using Minkowski functionals.
AB  - Point pattern sets arise in many different areas of physical, biological, and
      applied research, representing many random realizations of underlying pattern
      formation mechanisms. These pattern sets can be heterogeneous with respect to
      underlying spatial processes, which may not be visually distiguishable. This
      heterogeneity can be elucidated by looking at statistical measures of the
      patterns sets and using these measures to divide the pattern sets into distinct
      groups representing like spatial processes. We introduce here a numerical
      procedure for sorting point pattern sets into spatially homogenous groups using
      functional principal component analysis (FPCA) applied to the approximated
      Minkowski functionals of each pattern. We demonstrate that this procedure
      correctly sorts pattern sets into similar groups both when the patterns are drawn
      from similar processes and when the second-order characteristics of the pattern
      are identical. We highlight this routine for distinguishing the molecular
      patterning of fluorescently labeled cell membrane proteins, a subject of much
      interest in studies investigating complex spatial signaling patterns involved in
      the human immune response. 

PMID- 24032878
TI  - Effect of the interconnected network structure on the epidemic threshold.
AB  - Most real-world networks are not isolated. In order to function fully, they are
      interconnected with other networks, and this interconnection influences their
      dynamic processes. For example, when the spread of a disease involves two
      species, the dynamics of the spread within each species (the contact network)
      differs from that of the spread between the two species (the interconnected
      network). We model two generic interconnected networks using two adjacency
      matrices, A and B, in which A is a 2N*2N matrix that depicts the connectivity
      within each of two networks of size N, and B a 2N*2N matrix that depicts the
      interconnections between the two. Using an N-intertwined mean-field
      approximation, we determine that a critical susceptible-infected-susceptible
      (SIS) epidemic threshold in two interconnected networks is 1/lambda(1)(A+alphaB),
      where the infection rate is beta within each of the two individual networks and
      alphabeta in the interconnected links between the two networks and
      lambda(1)(A+alphaB) is the largest eigenvalue of the matrix A+alphaB. In order to
      determine how the epidemic threshold is dependent upon the structure of
      interconnected networks, we analytically derive lambda(1)(A+alphaB) using a
      perturbation approximation for small and large alpha, the lower and upper bound
      for any alpha as a function of the adjacency matrix of the two individual
      networks, and the interconnections between the two and their largest eigenvalues
      and eigenvectors. We verify these approximation and boundary values for
      lambda(1)(A+alphaB) using numerical simulations, and determine how component
      network features affect lambda(1)(A+alphaB). We note that, given two isolated
      networks G(1) and G(2) with principal eigenvectors x and y, respectively,
      lambda(1)(A+alphaB) tends to be higher when nodes i and j with a higher
      eigenvector component product x(i)y(j) are interconnected. This finding suggests
      essential insights into ways of designing interconnected networks to be robust
      against epidemics.

PMID- 24032879
TI  - Random walk with priorities in communicationlike networks.
AB  - We study a model for a random walk of two classes of particles (A and B). Where
      both species are present in the same site, the motion of A's takes precedence
      over that of B's. The model was originally proposed and analyzed in Maragakis et
      al. [Phys. Rev. E 77, 020103(R) (2008)]; here we provide additional results. We
      solve analytically the diffusion coefficients of the two species in lattices for
      a number of protocols. In networks, we find that the probability of a B particle
      to be free decreases exponentially with the node degree. In scale-free networks,
      this leads to localization of the B's at the hubs and arrest of their motion. To
      remedy this, we investigate several strategies to avoid trapping of the B's,
      including moving an A instead of the hindered B, allowing a trapped B to hop with
      a small probability, biased walk toward non-hub nodes, and limiting the capacity
      of nodes. We obtain analytic results for lattices and networks, and we discuss
      the advantages and shortcomings of the possible strategies. 

PMID- 24032880
TI  - Impact of compatibility on the organization of mutualistic networks.
AB  - Distinct relationships such as activation, inhibition, cooperation, and
      competition are not established independently but in a correlated manner in
      complex systems. Thus the patterns of one type of interaction may reflect the
      impacts of other classes of interactions, but its quantitative understanding
      remains to be done. Referring to the plant-pollinator mutualistic networks, here
      we propose and investigate the structural features of a model bipartite network,
      in which the mutualistic relationship between two different types of nodes is
      established under the influence of the compatibility among the nodes of the same
      type. Interestingly, we find that the degree distributions obtained for extremely
      broad compatibility distributions are similar to those for a constant
      compatibility, both of which deviate from those for the Gaussian compatibility
      distributions. We present the analytic arguments to explain this finding. Also
      the dependence of the topological similarity of two nodes on their compatibility
      is illustrated. We discuss the application of our findings to complex systems. 

PMID- 24032881
TI  - Motifs in triadic random graphs based on Steiner triple systems.
AB  - Conventionally, pairwise relationships between nodes are considered to be the
      fundamental building blocks of complex networks. However, over the last decade,
      the overabundance of certain subnetwork patterns, i.e., the so-called motifs, has
      attracted much attention. It has been hypothesized that these motifs, instead of
      links, serve as the building blocks of network structures. Although the relation
      between a network's topology and the general properties of the system, such as
      its function, its robustness against perturbations, or its efficiency in
      spreading information, is the central theme of network science, there is still a
      lack of sound generative models needed for testing the functional role of
      subgraph motifs. Our work aims to overcome this limitation. We employ the
      framework of exponential random graph models (ERGMs) to define models based on
      triadic substructures. The fact that only a small portion of triads can actually
      be set independently poses a challenge for the formulation of such models. To
      overcome this obstacle, we use Steiner triple systems (STSs). These are
      partitions of sets of nodes into pair-disjoint triads, which thus can be
      specified independently. Combining the concepts of ERGMs and STSs, we suggest
      generative models capable of generating ensembles of networks with nontrivial
      triadic Z-score profiles. Further, we discover inevitable correlations between
      the abundance of triad patterns, which occur solely for statistical reasons and
      need to be taken into account when discussing the functional implications of
      motif statistics. Moreover, we calculate the degree distributions of our triadic
      random graphs analytically. 

PMID- 24032882
TI  - Replicator dynamics with turnover of players.
AB  - We study adaptive dynamics in games where players abandon the population at a
      given rate and are replaced by naive players characterized by a prior
      distribution over the admitted strategies. We demonstrate how such a process
      leads macroscopically to a variant of the replicator equation, with an additional
      term accounting for player turnover. We study how Nash equilibria and the
      dynamics of the system are modified by this additional term for prototypical
      examples such as the rock-paper-scissors game and different classes of two-action
      games played between two distinct populations. We conclude by showing how player
      turnover can account for nontrivial departures from Nash equilibria observed in
      data from lowest unique bid auctions. 

PMID- 24032883
TI  - Costly bilingualism model in a population with one zealot.
AB  - We consider a costly bilingualism model in which one can take two strategies in
      parallel. We investigate how a single zealot triggers the cascading behavior and
      how the compatibility of the two strategies affects when interacting patterns
      change. First, the role of the interaction range in the cascading is studied by
      increasing the range from local to global. We find that people sometimes do not
      favor taking the superior strategy even though its payoff is higher than that of
      the inferior one. This is found to be caused by the local interactions rather
      than the global ones. Applying this model to social networks, we find that the
      location of the zealot is also important for larger cascading in heterogeneous
      networks. 

PMID- 24032884
TI  - Duality between equilibrium and growing networks.
AB  - In statistical physics any given system can be either at an equilibrium or away
      from it. Networks are not an exception. Most network models can be classified as
      either equilibrium or growing. Here we show that under certain conditions there
      exists an equilibrium formulation for any growing network model, and vice versa.
      The equivalence between the equilibrium and nonequilibrium formulations is exact
      not only asymptotically, but even for any finite system size. The required
      conditions are satisfied in random geometric graphs in general and causal sets in
      particular, and to a large extent in some real networks. 

PMID- 24032885
TI  - Effect of overpasses in the Biham-Middleton-Levine traffic flow model with random
      and parallel update rule.
AB  - The effect of overpasses in the Biham-Middleton-Levine traffic flow model with
      random and parallel update rules has been studied. An overpass is a site that can
      be occupied simultaneously by an eastbound car and a northbound one. Under
      periodic boundary conditions, both self-organized and random patterns are
      observed in the free-flowing phase of the parallel update model, while only the
      random pattern is observed in the random update model. We have developed mean
      field analysis for the moving phase of the random update model, which agrees with
      the simulation results well. An intermediate phase is observed in which some cars
      could pass through the jamming cluster due to the existence of free paths in the
      random update model. Two intermediate states are observed in the parallel update
      model, which have been ignored in previous studies. The intermediate phases in
      which the jamming skeleton is only oriented along the diagonal line in both
      models have been analyzed, with the analyses agreeing well with the simulation
      results. With the increase of overpass ratio, the jamming phase and the
      intermediate phases disappear in succession for both models. Under open boundary
      conditions, the system exhibits only two phases when the ratio of overpasses is
      below a threshold in the random update model. When the ratio of the overpass is
      close to 1, three phases could be observed, similar to the totally asymmetric
      simple exclusion process model. The dependence of the average velocity, the
      density, and the flow rate on the injection probability in the moving phase has
      also been obtained through mean-field analysis. The results of the parallel model
      under open boundary conditions are similar to that of the random update model. 

PMID- 24032886
TI  - Enhancing community integrity of networks against multilevel targeted attacks.
AB  - The community structure and the robustness are two important properties of
      networks for analyzing the functionality of complex systems. The community
      structure is crucial to understand the potential functionality of complex
      systems, while the robustness is indispensable to protect the functionality of
      complex systems from malicious attacks. When a network suffers from an
      unpredictable attack, its structural integrity would be damaged. Earlier studies
      focused on the integrity of the node structure or the edge structure when a
      network suffers from a single-level malicious attack on the nodes or the edges.
      In this study, we model the attack on the network as a two-level targeted one.
      Then, we propose a community robustness index to evaluate the integrality of the
      community structure when the network suffers from the modeled attack. The
      proposed index plays an important role in analyzing the ability of the real
      systems to resist unpredictable failures. Finally, based on the proposed
      community robustness index, a greedy algorithm is devised to mitigate the network
      attack. Experiments on three real network systems show that with minor changes in
      links the community robustness of networks can be greatly improved. The results
      also demonstrate that the community structures in the optimized networks remain
      practically unchanged compared with the original ones. 

PMID- 24032887
TI  - Continuous-time random walks on networks with vertex- and time-dependent forcing.
AB  - We have investigated the transport of particles moving as random walks on the
      vertices of a network, subject to vertex- and time-dependent forcing. We have
      derived the generalized master equations for this transport using continuous time
      random walks, characterized by jump and waiting time densities, as the underlying
      stochastic process. The forcing is incorporated through a vertex- and time
      dependent bias in the jump densities governing the random walking particles. As a
      particular case, we consider particle forcing proportional to the concentration
      of particles on adjacent vertices, analogous to self-chemotactic attraction in a
      spatial continuum. Our algebraic and numerical studies of this system reveal an
      interesting pair-aggregation pattern formation in which the steady state is
      composed of a high concentration of particles on a small number of isolated pairs
      of adjacent vertices. The steady states do not exhibit this pair aggregation if
      the transport is random on the vertices, i.e., without forcing. The manifestation
      of pair aggregation on a transport network may thus be a signature of self
      chemotactic-like forcing. 

PMID- 24032888
TI  - Gravity versus radiation models: on the importance of scale and heterogeneity in
      commuting flows.
AB  - We test the recently introduced radiation model against the gravity model for the
      system composed of England and Wales, both for commuting patterns and for public
      transportation flows. The analysis is performed both at macroscopic scales, i.e.,
      at the national scale, and at microscopic scales, i.e., at the city level. It is
      shown that the thermodynamic limit assumption for the original radiation model
      significantly underestimates the commuting flows for large cities. We then
      generalize the radiation model, introducing the correct normalization factor for
      finite systems. We show that even if the gravity model has a better overall
      performance the parameter-free radiation model gives competitive results,
      especially for large scales. 

PMID- 24032889
TI  - Slow epidemic extinction in populations with heterogeneous infection rates.
AB  - We explore how heterogeneity in the intensity of interactions between people
      affects epidemic spreading. For that, we study the susceptible-infected
      susceptible model on a complex network, where a link connecting individuals i and
      j is endowed with an infection rate beta(ij)=lambdaw(ij) proportional to the
      intensity of their contact w(ij), with a distribution P(w(ij)) taken from face-to
      face experiments analyzed in Cattuto et al. [PLoS ONE 5, e11596 (2010)]. We find
      an extremely slow decay of the fraction of infected individuals, for a wide range
      of the control parameter lambda. Using a distribution of width a we identify two
      large regions in the a-lambda space with anomalous behaviors, which are
      reminiscent of rare region effects (Griffiths phases) found in models with
      quenched disorder. We show that the slow approach to extinction is caused by
      isolated small groups of highly interacting individuals, which keep epidemics
      alive for very long times. A mean-field approximation and a percolation approach
      capture with very good accuracy the absorbing-active transition line for weak
      (small a) and strong (large a) disorder, respectively.

PMID- 24032890
TI  - Language change in a multiple group society.
AB  - The processes leading to change in languages are manifold. In order to reduce
      ambiguity in the transmission of information, agreement on a set of conventions
      for recurring problems is favored. In addition to that, speakers tend to use
      particular linguistic variants associated with the social groups they identify
      with. The influence of other groups propagating across the speech community as
      new variant forms sustains the competition between linguistic variants. With the
      utterance selection model, an evolutionary description of language change, Baxter
      et al. [Phys. Rev. E 73, 046118 (2006)] have provided a mathematical formulation
      of the interactions inside a group of speakers, exploring the mechanisms that
      lead to or inhibit the fixation of linguistic variants. In this paper, we take
      the utterance selection model one step further by describing a speech community
      consisting of multiple interacting groups. Tuning the interaction strength
      between groups allows us to gain deeper understanding about the way in which
      linguistic variants propagate and how their distribution depends on the group
      partitioning. Both for the group size and the number of groups we find scaling
      behaviors with two asymptotic regimes. If groups are strongly connected, the
      dynamics is that of the standard utterance selection model, whereas if their
      coupling is weak, the magnitude of the latter along with the system size governs
      the way consensus is reached. Furthermore, we find that a high influence of the
      interlocutor on a speaker's utterances can act as a counterweight to group
      segregation. 

PMID- 24032891
TI  - Decentralized routing on spatial networks with stochastic edge weights.
AB  - We investigate algorithms to find short paths in spatial networks with stochastic
      edge weights. Our formulation of the problem of finding short paths differs from
      traditional formulations because we specifically do not make two of the usual
      simplifying assumptions: (1) we allow edge weights to be stochastic rather than
      deterministic and (2) we do not assume that global knowledge of a network is
      available. We develop a decentralized routing algorithm that provides en route
      guidance for travelers on a spatial network with stochastic edge weights without
      the need to rely on global knowledge about the network. To guide a traveler, our
      algorithm uses an estimation function that evaluates cumulative arrival
      probability distributions based on distances between pairs of nodes. The
      estimation function carries a notion of proximity between nodes and thereby
      enables routing without global knowledge. In testing our decentralized algorithm,
      we define a criterion that makes it possible to discriminate among arrival
      probability distributions, and we test our algorithm and this criterion using
      both synthetic and real networks. 

PMID- 24032892
TI  - Dynamical influence processes on networks: general theory and applications to
      social contagion.
AB  - We study binary state dynamics on a network where each node acts in response to
      the average state of its neighborhood. By allowing varying amounts of
      stochasticity in both the network and node responses, we find different outcomes
      in random and deterministic versions of the model. In the limit of a large, dense
      network, however, we show that these dynamics coincide. We construct a general
      mean-field theory for random networks and show this predicts that the dynamics on
      the network is a smoothed version of the average response function dynamics.
      Thus, the behavior of the system can range from steady state to chaotic depending
      on the response functions, network connectivity, and update synchronicity. As a
      specific example, we model the competing tendencies of imitation and
      nonconformity by incorporating an off-threshold into standard threshold models of
      social contagion. In this way, we attempt to capture important aspects of
      fashions and societal trends. We compare our theory to extensive simulations of
      this "limited imitation contagion" model on Poisson random graphs, finding
      agreement between the mean-field theory and stochastic simulations. 

PMID- 24032893
TI  - Degree-based attacks are not optimal for desynchronization in general networks.
AB  - Suppressing harmful synchronization in complex networked systems is receiving
      increasing interest in various contexts including epileptic seizure and the
      Internet and traffic congestion. It is traditionally believed that by disrupting
      the most important nodes (i.e., those nodes of high degrees) synchronization can
      be effectively mitigated. However, this approach can perform poorly in more
      general situations such as homogeneous (random) or small world networks. In this
      article, we investigate how topological properties, such as the heterogeneity of
      the network can have an impact on its desynchronization. In particular, we
      propose a topology-aware scheme that chooses topologically sufficiently
      diversified contrarian nodes by taking into account the patterns of connectivity
      among them. Hence, a maximal number of nodes in the network can be influenced,
      leading to a more global impact and greater disruption to synchronization. Our
      scheme demonstrates significantly improved performance on various networked
      systems including homogeneous networks, small world, and even scale-free
      networks. 

PMID- 24032894
TI  - Spontaneous scale-free structure in adaptive networks with synchronously
      dynamical linking.
AB  - Inspired by the anti-Hebbian learning rule in neural systems, we study how the
      feedback from dynamical synchronization shapes network structure by adding new
      links. Through extensive numerical simulations, we find that an adaptive network
      spontaneously forms scale-free structure, as confirmed in many real systems.
      Moreover, the adaptive process produces two nontrivial power-law behaviors of
      deviation strength from mean activity of the network and negative degree
      correlation, which exists widely in technological and biological networks.
      Importantly, these scalings are robust to variation of the adaptive network
      parameters, which may have meaningful implications in the scale-free formation
      and manipulation of dynamical networks. Our study thus suggests an alternative
      adaptive mechanism for the formation of scale-free structure with negative degree
      correlation, which means that nodes of high degree tend to connect, on average,
      with others of low degree and vice versa. The relevance of the results to
      structure formation and dynamical property in neural networks is briefly
      discussed as well. 

PMID- 24032895
TI  - Nonlinear stability of traffic models and the use of Lyapunov vectors for
      estimating the traffic state.
AB  - Valuable information for estimating the traffic flow is obtained with current GPS
      technology by monitoring position and velocity of vehicles. In this paper, we
      present a proof of concept study that shows how the traffic state can be
      estimated using only partial and noisy data by assimilating them in a dynamical
      model. Our approach is based on a data assimilation algorithm, developed by the
      authors for chaotic geophysical models, designed to be equivalent but
      computationally much less demanding than the traditional extended Kalman filter.
      Here we show that the algorithm is even more efficient if the system is not
      chaotic and demonstrate by numerical experiments that an accurate reconstruction
      of the complete traffic state can be obtained at a very low computational cost by
      monitoring only a small percentage of vehicles. 

PMID- 24032896
TI  - Chaotic scattering on individual quantum graphs.
AB  - For chaotic scattering on quantum graphs, the semiclassical approximation is
      exact. We use this fact and employ supersymmetry, the color-flavor
      transformation, and the saddle-point approximation to calculate the exact
      expression for the lowest and asymptotic expressions in the Ericson regime for
      all higher correlation functions of the scattering matrix. Our results agree with
      those available from the random-matrix approach to chaotic scattering. We
      conjecture that our results hold universally for quantum-chaotic scattering. 

PMID- 24032897
TI  - Intermittent explosions of dissipative solitons and noise-induced crisis.
AB  - Dissipative solitons show a variety of behaviors not exhibited by their
      conservative counterparts. For instance, a dissipative soliton can remain
      localized for a long period of time without major profile changes, then grow and
      become broader for a short time-explode-and return to the original spatial
      profile afterward. Here we consider the dynamics of dissipative solitons and the
      onset of explosions in detail. By using the one-dimensional complex Ginzburg
      Landau model and adjusting a single parameter, we show how the appearance of
      explosions has the general signatures of intermittency: the periods of time
      between explosions are irregular even in the absence of noise, but their mean
      value is related to the distance to criticality by a power law. We conjecture
      that these explosions are a manifestation of attractor-merging crises, as the
      continuum of localized solitons induced by translation symmetry becomes connected
      by short-lived trajectories, forming a delocalized attractor. As additive noise
      is added, the extended system shows the same scaling found by low-dimensional
      systems exhibiting crises [J. Sommerer, E. Ott, and C. Grebogi, Phys. Rev. A 43,
      1754 (1991)], thus supporting the validity of the proposed picture. 

PMID- 24032898
TI  - Resonance energy transport and exchange in oscillator arrays.
AB  - It is well known that complete energy transfer between two weakly coupled linear
      oscillators occurs only at resonance. If the oscillators are nonlinear, the
      amplitude dependence of their frequencies may destroy, in general, any eventual
      resonance. This means that no substantial energy transfer may occur unless,
      exceptionally, resonance persists during the transfer. In this paper, the self
      sustained resonance is considered for an oscillator array consisting of n coupled
      linear oscillators (a primary system) initially excited by impulse loading and
      connected to an essentially nonlinear attachment (NLA). Under the condition of
      resonance, initial energy is transferred to the NLA and then travels back and
      forth between the linear and nonlinear oscillators. It is shown that the general
      mechanism of the energy transport is similar to that in the previously studied
      system of two coupled oscillators but, in contrast to the two degree-of-freedom
      case, the multidimensional system requires a proper tuning not only for the NLA
      but for the entire array. In this work, we develop an order-reduction procedure,
      which allows the separated dynamical analysis for the pair of nonlinearly coupled
      oscillators and the remaining (n-1) linear oscillators. Using simplifications
      based on the low-order reduced model, we detect an admissible domain of
      parameters ensuring resonance interaction and then derive a closed-form
      approximate solution adequately describing the transient processes in the entire
      system. We obtain explicit approximate solutions for both conservative (complete
      energy exchange) and dissipative (irreversible energy transfer) systems and then
      illustrate the theoretical results by an example of the four degree-of-freedom
      system. Analytical results are confirmed by numerical simulations. 

PMID- 24032899
TI  - Wave competitions around interfaces of two oscillatory media.
AB  - Wave competition is an important phenomenon for pattern formation and pattern
      control, which are required in many practical applications. In this work we
      consider the competition of wave trains around interfaces of two one-dimensional
      oscillatory media, modeled by complex Ginzburg-Landau equations with different
      system control parameters. The wave trains are generated by pacings at two
      boundaries of the media. In the presence of both normal wave trains and antiwave
      trains, extremely rich phenomena can be observed by varying the control
      parameters of the systems. These rich behaviors can be fully understood and
      physically well explained, based on the competitions of three kinds of wave
      trains: the two wave trains generated by external pacings and the wave train
      generated internally at the interface. 

PMID- 24032900
TI  - Persistence of uphill anomalous transport in inhomogeneous media.
AB  - For systems out of equilibrium and subjected to a static bias force it can often
      be expected that particle transport will usually follow the direction of this
      bias. However, counterexamples exist where particles exhibit uphill motion (known
      as absolute negative mobility, ANM), particularly in the case of coupled
      particles. Examples in single particle deterministic systems are less common.
      Recently, in one such example, uphill motion was shown to occur for an inertial
      driven and damped particle in a spatially symmetric periodic potential. The
      source of this anomalous transport was a combination of two periodic driving
      signals which together are asymmetric under time reversal. In this paper we
      investigate the phenomena of ANM for a deterministic particle evolving in a
      periodic and symmetric potential subjected to an external unbiased periodic
      driving and nonuniform space-dependent damping. It will be shown that this system
      exhibits a complicated response behavior as certain control parameters are
      varied, most notably being enhanced parameter regimes exhibiting ANM as the
      static bias force is increased. Moreover, the solutions exhibiting ANM are shown
      to be, at least over intermediate time periods, superdiffusive, in contrast to
      the solutions that follow the bias where the diffusion is normal. 

PMID- 24032901
TI  - Chaos and ergodicity of two hard disks within a circular billiard.
AB  - We investigate dynamical properties of the system of two interacting hard disks
      within a circular billiard numerically in the case of zero total angular
      momentum. Varying the radius of two identical disks, we examine chaotic
      irregularity and ergodicity of the system. Single-particle configuration and
      velocity distributions are obtained from dynamical trajectory calculations and
      compared with those in the microcanonical ensemble. We also analyze properties of
      trajectories by calculating the finite-time maximum Lyapunov exponent and clarify
      the existence of sticky motions around Kolmogorov-Arnold-Moser (KAM) tori even
      for small radii of disks. It is shown that the present system is almost ergodic
      in spite of the existence of tori for small radii of disks since the ratio of
      tori to the whole phase space is extremely small. On the other hand, a number of
      tori increase abruptly as the radius of disks increases beyond some value and
      tori prevent trajectories to run over the phase space uniformly, which makes the
      ergodicity of the system broken down. 

PMID- 24032902
TI  - Synchronization of a Josephson junction array in terms of global variables.
AB  - We consider an array of Josephson junctions with a common LCR load. Application
      of the Watanabe-Strogatz approach [Physica D 74, 197 (1994)] allows us to
      formulate the dynamics of the array via the global variables only. For identical
      junctions this is a finite set of equations, analysis of which reveals the
      regions of bistability of the synchronous and asynchronous states. For disordered
      arrays with distributed parameters of the junctions, the problem is formulated as
      an integro-differential equation for the global variables; here stability of the
      asynchronous states and the properties of the transition synchrony-asynchrony are
      established numerically. 

PMID- 24032903
TI  - Correlation properties of exactly solvable chaotic oscillators.
AB  - We derive exact expressions for the autocorrelation and cross-correlation
      functions of wave forms generated by two exactly solvable chaotic systems. For
      each system, an analytic expression exists for chaotic solutions, which we use to
      evaluate correlation integrals explicitly. For some specific parameter values, we
      calculate the mean and variance of the correlation functions averaged over all
      possible solutions. The mean autocorrelation is shown to decay at a rate equal to
      the Kolmogorov-Sinai entropy. All derived results are shown to agree with
      numerical calculations of the corresponding quantities. 

PMID- 24032904
TI  - Bistability and chaos at low levels of quanta.
AB  - We study nonlinear phenomena of bistability and chaos at a level of few quanta.
      For this purpose, we consider a single-mode dissipative oscillator with strong
      Kerr nonlinearity with respect to the dissipation rate driven by a monochromatic
      force as well as by a train of Gaussian pulses. The quantum effects and
      decoherence in the oscillatory mode are investigated in the framework of the
      purity of states and the Wigner functions calculated from the master equation. We
      demonstrate the quantum chaotic regime by means of a comparison between the
      contour plots of the Wigner functions and the strange attractors on the classical
      Poincare section. Considering bistability at a low limit of quanta, we analyze
      the minimal level of excitation numbers at which the bistable regime of the
      system is displayed. We also discuss the formation of an oscillatory chaotic
      regime by varying oscillatory excitation numbers at ranges of a few quanta. We
      demonstrate quantum-interference phenomena that are assisted hysteresis-cycle
      behavior and quantum chaos for the oscillator driven by a train of Gaussian
      pulses. We establish the border of quantum-classical correspondence for chaotic
      regimes in the case of strong nonlinearities. 

PMID- 24032905
TI  - Information directionality in coupled time series using transcripts.
AB  - In ordinal symbolic dynamics, transcripts describe the algebraic relationship
      between ordinal patterns. Using the concept of transcript, we exploit the
      mathematical structure of the group of permutations to derive properties and
      relations among information measures of the symbolic representations of time
      series. These theoretical results are then applied for the assessment of coupling
      directionality in dynamical systems, where suitable coupling directionality
      measures are introduced depending only on transcripts. These measures improve the
      reliability of the information flow estimates and reduce to well-established
      coupling directionality quantifiers when some general conditions are satisfied.
      Furthermore, by generalizing the definition of transcript to ordinal patterns of
      different lengths, several of the commonly used information directionality
      measures can be encompassed within the same framework. 

PMID- 24032906
TI  - Nonlinear localized modes in two-dimensional electrical lattices.
AB  - We report the observation of spontaneous localization of energy in two spatial
      dimensions in the context of nonlinear electrical lattices. Both stationary and
      moving self-localized modes were generated experimentally and theoretically in a
      family of two-dimensional square as well as honeycomb lattices composed of 6 * 6
      elements. Specifically, we find regions in driver voltage and frequency where
      stationary discrete breathers, also known as intrinsic localized modes (ILMs),
      exist and are stable due to the interplay of damping and spatially homogeneous
      driving. By introducing additional capacitors into the unit cell, these lattices
      can controllably induce mobile discrete breathers. When more than one such ILMs
      are experimentally generated in the lattice, the interplay of nonlinearity,
      discreteness, and wave interactions generates a complex dynamics wherein the ILMs
      attempt to maintain a minimum distance between one another. Numerical simulations
      show good agreement with experimental results and confirm that these phenomena
      qualitatively carry over to larger lattice sizes. 

PMID- 24032907
TI  - Fractal dynamics in chaotic quantum transport.
AB  - Despite several experiments on chaotic quantum transport in two-dimensional
      systems such as semiconductor quantum dots, corresponding quantum simulations
      within a real-space model have been out of reach so far. Here we carry out
      quantum transport calculations in real space and real time for a two-dimensional
      stadium cavity that shows chaotic dynamics. By applying a large set of magnetic
      fields we obtain a complete picture of magnetoconductance that indicates fractal
      scaling. In the calculations of the fractality we use detrended fluctuation
      analysis-a widely used method in time-series analysis-and show its usefulness in
      the interpretation of the conductance curves. Comparison with a standard method
      to extract the fractal dimension leads to consistent results that in turn
      qualitatively agree with the previous experimental data. 

PMID- 24032908
TI  - Dynamics of self-organized driven particles with competing range interaction.
AB  - Nonequilibrium self-organized patterns formed by particles interacting through
      competing range interaction are driven over a substrate by an external force. We
      show that, with increasing driving force, the preexisted static patterns evolve
      into dynamic patterns either via disordered phase or depinned patterns or via the
      formation of nonequilibrium stripes. Strikingly, the stripes are formed either in
      the direction of the driving force or in the transverse direction, depending on
      the pinning strength. The revealed dynamical patterns are summarized in a
      dynamical phase diagram. 

PMID- 24032909
TI  - Radial sine-Gordon kinks as sources of fast breathers.
AB  - We consider radial sine-Gordon kinks in two, three, and higher dimensions. A full
      two-dimensional simulation showing that azimuthal perturbations remain small
      allows us to reduce the problem to the one-dimensional radial sine-Gordon
      equation. We solve this equation on an interval [r(0),r(1)] and absorb all
      outgoing radiation. As the kink shrinks toward r(0), before the collision, its
      motion is well described by a simple law derived from the conservation of energy.
      In two dimensions for r(0)<=2, the collision disintegrates the kink into a fast
      breather, while for r(0)>=4 we obtain a kink-breather metastable state where
      breathers are shed at each kink "return." In three and higher dimensions d, an
      additional kink-oscillon state appears for small r(0). On the application side,
      the kink disintegration opens the way for new types of terahertz microwave
      generators.

PMID- 24032910
TI  - Semiclassical wave functions for open quantum billiards.
AB  - We present a semiclassical approximation to the scattering wave function Psi(r,k)
      for an open quantum billiard, which is based on the reconstruction of the Feynman
      path integral. We demonstrate its remarkable numerical accuracy for the open
      rectangular billiard and show that the convergence of the semiclassical wave
      function to the full quantum state is controlled by the mean path length or
      equivalently the dwell time for a given scattering state. In the numerical
      implementation a cutoff length in the maximum path length or, equivalently, a
      maximum dwell time tau(max) included implies a finite energy resolution
      DeltaE~tau(max)(-1). Possible applications include leaky billiards and systems
      with decoherence present.

PMID- 24032911
TI  - Double-discrete solitons in fishnet arrays of optical fibers.
AB  - We demonstrate that crossed arrays of optical fibers support the double-discrete
      linear and nonlinear propagation of light beams, in which not only the transverse
      coordinate (the fiber's number) is discrete, but also the longitudinal
      (propagation) coordinate, i.e., the number of the fiber-crossing site, is
      effectively discrete too. In the linear limit, this transmission regime features
      double-discrete self-collimation. The nonlinear fishnet arrays with both focusing
      and defocusing nonlinearities give rise to double-discrete spatial solitons.
      Solitons bifurcating from two different branches of the linear dispersion
      relation feature strong interactions and form composite states. In the continuum
      limit, the model of the nonlinear fishnet reduces to a system of coupled-mode
      equations similar to those describing Bragg gratings, but without the cross-phase
      modulation terms. 

PMID- 24032912
TI  - Akhmediev breathers, Ma solitons, and general breathers from rogue waves: a case
      study in the Manakov system.
AB  - We present explicit forms of general breather (GB), Akhmediev breather (AB), Ma
      soliton (MS), and rogue wave (RW) solutions of the two-component nonlinear
      Schrodinger (NLS) equation, namely Manakov equation. We derive these solutions
      through two different routes. In the forward route, we first construct a suitable
      periodic envelope soliton solution to this model from which we derive GB, AB, MS,
      and RW solutions. We then consider the RW solution as the starting point and
      derive AB, MS, and GB in the reverse direction. The second approach has not been
      illustrated so far for the two component NLS equation. Our results show that the
      above rational solutions of the Manakov system can be derived from the standard
      scalar nonlinear Schrodinger equation with a modified nonlinearity parameter.
      Through this two-way approach we establish a broader understanding of these
      rational solutions, which will be of interest in a variety of situations. 

PMID- 24032913
TI  - Solvable model for solitons pinned to a parity-time-symmetric dipole.
AB  - We introduce the simplest one-dimensional nonlinear model with parity-time (PT)
      symmetry, which makes it possible to find exact analytical solutions for
      localized modes ("solitons"). The PT-symmetric element is represented by a
      pointlike (delta-functional) gain-loss dipole ~delta'(x), combined with the usual
      attractive potential ~delta(x). The nonlinearity is represented by self-focusing
      (SF) or self-defocusing (SDF) Kerr terms, both spatially uniform and localized.
      The system can be implemented in planar optical waveguides. For the sake of
      comparison, also introduced is a model with separated delta-functional gain and
      loss, embedded into the linear medium and combined with the delta-localized Kerr
      nonlinearity and attractive potential. Full analytical solutions for pinned modes
      are found in both models. The exact solutions are compared with numerical
      counterparts, which are obtained in the gain-loss-dipole model with the delta'
      and delta functions replaced by their Lorentzian regularization. With the
      increase of the dipole's strength gamma, the single-peak shape of the numerically
      found mode, supported by the uniform SF nonlinearity, transforms into a double
      peak. This transition coincides with the onset of the escape instability of the
      pinned soliton. In the case of the SDF uniform nonlinearity, the pinned modes are
      stable, keeping the single-peak shape.

PMID- 24032914
TI  - Attractive and repulsive contributions of localized excitability inhomogeneities
      and elimination of spiral waves in excitable media.
AB  - The attracting and repelling of spiral waves in a two-dimensional excitable
      medium in the presence of localized excitability inhomogeneities are studied. The
      choice of two effects depends on the comparison of excitabilities inside and
      outside the localized obstacle. We inspect the changes in attracting and
      repelling behaviors with respect to the size of the obstacle and the initial
      distance between the center of the spiral core and the obstacle. To understand
      the occurrence of these phenomena, we investigated the small v-value areas near
      the tip and the function of the wave velocity as the excitability parameter
      epsilon. Considering the attributes of the attractive obstacle, an eliminating
      scheme of spiral waves is proposed in which the attractive obstacle is rapidly
      moved at several fixed times. This method can avoid the high-amplitude and high
      frequency stimulus in most conventional methods.

PMID- 24032915
TI  - Moving Bragg grating solitons in a cubic-quintic nonlinear medium with dispersive
      reflectivity.
AB  - The stability and collision dynamics of moving solitons in Bragg gratings with
      cubic-quintic nonlinearity and dispersive reflectivity are investigated. Two
      disjoint families of solitons are found on the plane of the coefficient of
      quintic nonlinearity versus the normalized frequency (eta,Omega(norm)). Through
      numerical stability analysis, we have identified stability regions on the
      (eta,Omega(norm)) plane for various values of dispersive reflectivity parameter
      (m) and velocity (v). The size of stability regions is found to be dependent on m
      and v. Collisions of counterpropgating Type 1 and Type 2 solitons have been
      systematically investigated. It is found that for low to moderate values of
      dispersive reflectivity, the collisions of Type 1 solitons can result in various
      outcomes such as separation of solitons with reduced, increased, unchanged, or
      asymmetric velocities and generation of a quiescent soliton by merger or
      formation of three solitons. For strong dispersive reflectivity (e.g., m=0.5),
      the collisions of low-velocity in-phase Type 1 solitons may lead to repulsion of
      solitons, asymmetric separation, merger into a single soliton, or formation of
      three solitons (one quiescent and two moving solitons). At higher velocities
      collisions predominantly lead to the formation of three solitons. For m=0.5, in
      phase Type 2 solitons may repel or form a temporary bound state of quiescent Type
      1 solitons that subsequently splits into two asymmetrically separating Type 1
      solitons. pi-out-of-phase Type 2 solitons may also merge to form a quiescent Type
      1 soliton.

PMID- 24032916
TI  - Barycentric fixed-mass method for multifractal analysis.
AB  - We present a method to estimate the multifractal spectrum of point distributions.
      The method incorporates two motivated criteria (barycentric pivot point selection
      and nonoverlapping coverage) in order to reduce edge effects, improve precision,
      and reduce computation time. Implementation of the method on synthetic benchmarks
      demonstrates the superior performance of the proposed method compared with
      existing alternatives routinely used in the literature. Finally, we use the
      method to estimate the multifractal properties of the widely studied growth
      process of diffusion-limited aggregation (DLA) and compare our results with
      recent and earlier studies. Our tests support the conclusion of a genuine but
      weak multifractality of the central core of DLA clusters, with D(q) decreasing
      from 1.75+/-0.01 for q=-10 to 1.65+/-0.01 for q =+10.

PMID- 24032917
TI  - Control of excitable pulses in an injection-locked semiconductor laser.
AB  - In spite of numerous theoretical and experimental reports of excitability in
      lasers with injected signal based on the locking-unlocking transition, the
      response of the system to controlled external perturbations (which is at the
      basis of the definition of excitable systems) has not been experimentally studied
      yet. In the following, we analyze the response of an injection-locked
      semiconductor laser to different external perturbations. We demonstrate the
      existence of a perturbation threshold beyond which the response of the system is
      independent of the strength of the stimulation and, thus, demonstrate its
      excitable character. We show that optically perturbing such an excitable system
      via the control of the phase of the injection beam can be useful for optical
      pulse generation. 

PMID- 24032918
TI  - Finger competition in lifting Hele-Shaw flows with a yield stress fluid.
AB  - A weakly nonlinear approach is used to investigate interfacial pattern formation
      in a lifting Hele-Shaw cell containing a yield stress fluid surrounded by a fluid
      of negligible viscosity. By considering the onset of nonlinear effects and the
      regime in which viscous effects dominate over yield stress, we study how the
      system responds to changes in two controlling dimensionless parameters: (i) the
      geometric aspect ratio (ratio of the initially circular radius of the fluid-fluid
      interface to the initial Hele-Shaw cell plate spacing), and (ii) a yield stress
      parameter (relative measure of yield stress to viscous forces). Within this
      context, we discuss how these key factors influence interface stability and
      finger competition dynamics during early linear and intermediate stages of
      pattern evolution. 

PMID- 24032919
TI  - Simple model of the Rayleigh-Taylor instability, collapse, and structural
      elements.
AB  - The mechanisms and structural elements of the Rayleigh-Taylor instability whose
      evolution results in the occurrence of the collapse have been studied in the
      scope of the rotating shallow water model with horizontal density gradient.
      Analysis of the instability mechanism shows that two collapse scenarios are
      possible. One scenario implies anisotropic collapse during which the contact area
      of a collapsing fragment with the bottom contracts into a spinning segment. The
      other implies isotropic contracting of the area into a point. The rigorous
      integral criteria and power laws of collapses are found. 

PMID- 24032920
TI  - Asymptotic and numerical analysis of electrohydrodynamic flows of dielectric
      liquid.
AB  - We perform an asymptotic analysis of electrohydrodynamic (EHD) flow of nonpolar
      liquid subjected to an external, nonuniform electric field. The domain of
      interest covers the bulk as well as the thin dissociation layers (DSLs) near the
      electrodes. Outer (i.e., bulk) equations for the ion transport in hierarchical
      order of perturbation parameters can be expressed in linear form, whereas the
      inner (i.e., DSL) equations take a nonlinear form. We derive a simple formula in
      terms of various parameters which can be used to estimate the relative importance
      of the DSL-driven flow compared with the bulk-driven flow. EHD flow over a pair
      of cylindrical electrodes is then solved asymptotically and numerically. It is
      found that in large geometric scale and high ion concentration the EHD flow is
      dominated by the bulk-charge-induced flow. As the scale and concentration are
      decreased, the DSL-driven slip velocity increases and the resultant flow tends to
      dominate the domain and finally leads to flow reversal. We also conduct a flow
      visualization experiment to verify the analysis and attain good agreement between
      the two results with parameter tuning. We finally show, based on the comparison
      of experimental and numerical solutions, that the rate of free-ion generation
      (dissociation) should be less than the one predicted from the existing formula. 

PMID- 24032921
TI  - Effective slip-length tensor for a flow over weakly slipping stripes.
AB  - We discuss the flow past a flat heterogeneous solid surface decorated by slipping
      stripes. The spatially varying slip length, b(y), is assumed to be small compared
      to the scale of the heterogeneities, L, but finite. For such weakly slipping
      surfaces, earlier analyses have predicted that the effective slip length is
      simply given by the surface-averaged slip length, which implies that the
      effective slip-length tensor becomes isotropic. Here we show that a different
      scenario is expected if the local slip length has steplike jumps at the edges of
      slipping heterogeneities. In this case, the next-to-leading term in an expansion
      of the effective slip-length tensor in powers of max[b(y)/L] becomes comparable
      to the leading-order term, but anisotropic, even at very small b(y)/L. This leads
      to an anisotropy of the effective slip and to its significant reduction compared
      to the surface-averaged value. The asymptotic formulas are tested by numerical
      solutions and are in agreement with results of dissipative particle dynamics
      simulations. 

PMID- 24032922
TI  - Instability of streaks in pipe flow of shear-thinning fluids.
AB  - This study is motivated by recent experimental results dealing with the
      transition to turbulence in a pipe flow of shear-thinning fluids, where a streaky
      flow with an azimuthal wave number n=1 is observed in the transitional regime.
      Here, a linear stability analysis of pipe flow of shear-thinning fluids modulated
      azimuthally by finite amplitude streaks is performed. The shear-thinning behavior
      of the fluid is described by the Carreau model. The streaky base flows considered
      are obtained from two-dimensional direct numerical simulation using finite
      amplitude longitudinal rolls as the initial condition and by extracting the
      velocity field at time t(max), where the amplitude of the streaks reaches its
      maximum, denoted by A(max). It is found that the amplitude A(max) increases with
      increasing Reynolds number as well as with increasing amplitude E(0) of the
      initial longitudinal rolls. For sufficiently large streaks amplitude, streamwise
      velocity profiles develop inflection points, leading to instabilities. Depending
      on the threshold amplitude A(c), two different modes may trigger the instability
      of the streaks. If A(c) exceeds approximately 41.5% of the centerline velocity,
      the instability mode is located near the axis of the pipe, i.e., it is a "center
      mode." For weaker amplitude A(c), the instability mode is located near the pipe
      wall, in the region of highest wall normal shear, i.e., it is a "wall mode." The
      threshold amplitude A(c) decreases with increasing shear-thinning effects. The
      energy equation analysis indicates that (i) wall modes are driven mainly by the
      work of the Reynolds stress against the wall normal shear and (ii) for center
      modes, the contribution of the normal wall shear remains dominant; however, it is
      noted that the contribution of the Reynolds stress against the azimuthal shear
      increases with increasing shear-thinning effects.

PMID- 24032923
TI  - Ultrasound-induced acoustophoretic motion of microparticles in three dimensions.
AB  - We derive analytical expressions for the three-dimensional (3D) acoustophoretic
      motion of spherical microparticles in rectangular microchannels. The motion is
      generated by the acoustic radiation force and the acoustic streaming-induced drag
      force. In contrast to the classical theory of Rayleigh streaming in shallow,
      infinite, parallel-plate channels, our theory does include the effect of the
      microchannel side walls. The resulting predictions agree well with numerics and
      experimental measurements of the acoustophoretic motion of polystyrene spheres
      with nominal diameters of 0.537 and 5.33 MUm. The 3D particle motion was recorded
      using astigmatism particle tracking velocimetry under controlled thermal and
      acoustic conditions in a long, straight, rectangular microchannel actuated in one
      of its transverse standing ultrasound-wave resonance modes with one or two half
      wavelengths. The acoustic energy density is calibrated in situ based on
      measurements of the radiation dominated motion of large 5-MUm-diameter particles,
      allowing for quantitative comparison between theoretical predictions and
      measurements of the streaming-induced motion of small 0.5-MUm-diameter particles.

PMID- 24032924
TI  - Dynamics of squeezing fluids: clapping wet hands.
AB  - Droplets splash around when a fluid volume is quickly compressed. This phenomenon
      has been observed during common activities such as kids clapping with wet hands.
      The underlying mechanism involves a fluid volume being compressed vertically
      between two objects. This compression causes the fluid volume to be ejected
      radially and thereby generate fluid threads and droplets at a high speed. In this
      study, we designed and performed laboratory experiments to observe the process of
      thread and drop formation after a fluid is squeezed. A thicker rim at the outer
      edge forms and moves after the squeezing, and then becomes unstable and breaks
      into smaller drops. This process differs from previous well-known examples (i.e.,
      transient crown splashes and continuous water bells) in aspects of transient
      fluid feeding, expanding rim dynamics, or sparsely distributed drops. We compared
      experimental measurements with theoretical models over three different stages;
      early squeezing, intermediate sheet-expansion, and later break-up of the liquid
      thread. In the earlier stage, the fluid is squeezed and its initial velocity is
      governed by the lubrication force. The outer rim of the liquid sheet forms curved
      trajectories due to gravity, inertia, drag, and surface tension. At the late
      stage, drop spacing set by the initial capillary instability does not change in
      the course of rim expansion, consequently final ejected droplets are very sparse
      compared to the size of the rim. 

PMID- 24032925
TI  - Three-sphere magnetic swimmer in a shear flow.
AB  - We consider a low-Reynolds-number swimmer made from three spheres linked by two
      slender arms, and explore its motion in a shear flow. This rodlike three-sphere
      swimmer finally follows the direction dictated by the shear flow. To overcome
      this shortcoming, we propose a model in which the two outer spheres have
      permanent magnetic moments along the arms. This magnetic swimmer can be navigated
      to a desired direction by applying an external static and uniform magnetic field.

PMID- 24032926
TI  - Vibrations of cylindrical objects obstructing a Poiseuille-type flow.
AB  - Using the lattice Boltzmann equation, we numerically studied the dynamics of a
      physical model system, the Poiseuille flow-induced vibrations (PFIV). At a
      moderate Reynolds number, for flows past a cylinder that is free to move in the
      cross-flow direction while being fixed in the streamwise direction, between two
      parallel walls, a variety of distinct vibration regimes involving symmetrical
      periodic vibration, deflective quasiperiodic vibration, and deflective periodic
      vibration with corresponding wake states were observed. The data analysis shows
      that the distribution of the lift coefficient depending on the blockage ratio
      plays an important role in such a system. A further study of the case of two side
      by-side identical cylinders demonstrates the existence of two distinct
      cooperative vibrations of the cylinders, e.g., in-phase-synchronized vibration
      (IPSV) and anti-phase-synchronized vibration (APSV). The result reveals that
      there is a critical blockage ratio, beyond which a phase transition between IPSV
      and APSV occurs. For the phenomena observed here, PFIV can be considered a new
      type of vortex-induced vibration, and such a system is expected to find
      applications in fluid mixing. 

PMID- 24032927
TI  - Transition to chaos of natural convection between two infinite differentially
      heated vertical plates.
AB  - Natural convection of air between two infinite vertical differentially heated
      plates is studied analytically in two dimensions (2D) and numerically in two and
      three dimensions (3D) for Rayleigh numbers Ra up to 3 times the critical value
      Ra(c)=5708. The first instability is a supercritical circle pitchfork bifurcation
      leading to steady 2D corotating rolls. A Ginzburg-Landau equation is derived
      analytically for the flow around this first bifurcation and compared with results
      from direct numerical simulation (DNS). In two dimensions, DNS shows that the
      rolls become unstable via a Hopf bifurcation. As Ra is further increased, the
      flow becomes quasiperiodic, and then temporally chaotic for a limited range of
      Rayleigh numbers, beyond which the flow returns to a steady state through a
      spatial modulation instability. In three dimensions, the rolls instead undergo
      another pitchfork bifurcation to 3D structures, which consist of transverse rolls
      connected by counter-rotating vorticity braids. The flow then becomes time
      dependent through a Hopf bifurcation, as exchanges of energy occur between the
      rolls and the braids. Chaotic behavior subsequently occurs through two competing
      mechanisms: a sequence of period-doubling bifurcations leading to intermittency
      or a spatial pattern modulation reminiscent of the Eckhaus instability.

PMID- 24032928
TI  - Influence of granular packing on porosity and tortuosity.
AB  - In a granular porous medium the packing configuration and the shape of the grains
      influence how fluid flows through it. This is directly related to the porosity
      and tortuosity of the pore space. In this paper we present an analytical function
      relating the porosity phi and the tortuosity tau of a granular pore medium by
      means of a packing parameter B. A general expression to estimate B for different
      representative elementary volumes and grain shapes is presented; in particular,
      for polyhedral packings. Exploring the packing parameter properties, we discuss
      the nonuniqueness of the packing-shape combination in relation to B and the
      porosity behavior for the special cases 0<B<1, B=1, and B>1.

PMID- 24032929
TI  - Synchronization of rigid microrotors by time-dependent hydrodynamic interactions.
AB  - We investigate the emergent dynamical behavior of hydrodynamically coupled
      microrotors. The two rotors are confined in a plane and move along circles driven
      by active forces. The three-dimensional fluid is described by the linearized,
      time-dependent Navier-Stokes equations instead of the usually adopted Stokes
      equations. We demonstrate that time-dependent hydrodynamic interactions lead to
      synchronization of the rotational motion. The time dependence of the phase
      difference between the rotors is determined and synchronization times are
      extracted for various external torques and rotor separations by solving the
      underlaying integrodifferential equations numerically. In addition, an analytical
      expression is provided for the synchronization time. 

PMID- 24032930
TI  - Thick drops on a slowly oscillating substrate.
AB  - We examine the evolution of a liquid drop on an inclined substrate oscillating
      vertically. The oscillations are weak and slow, which makes the liquid's inertia
      and viscosity negligible (so that the drop's shape is determined by a balance of
      surface tension, gravity, and vibration-induced inertial force). No assumptions
      are made about the drop's thickness, which extends our previous results on thin
      drops [Benilov, Phys. Rev. E 84, 066301 (2011)] to more realistic situations. It
      is shown that, if the amplitude of the substrate's oscillations exceeds a certain
      threshold value epsilon(*), the drop climbs uphill. epsilon(*), however, strongly
      depends on the thickness of the drop, which, in turn, depends on the liquid's
      equilibrium contact angle beta[over -]. In particular, there is a dramatic
      decrease in epsilon(*) when beta[over -] exceeds a certain threshold, which means
      that thick drops climb uphill for a much weaker vibration of the substrate. At
      the same time, the frequency range of the substrate's vibration within which
      drops climb uphill becomes much narrower.

PMID- 24032931
TI  - Formation of curvature singularities on the interface between dielectric liquids
      in a strong vertical electric field.
AB  - The nonlinear dynamics of the interface between two deep dielectric fluids in the
      presence of a vertical electric field is studied. We consider the limit of a
      strong external electric field where electrostatic forces dominate over
      gravitational and capillary forces. The nonlinear integrodifferential equations
      for the interface motion are derived under the assumption of small interfacial
      slopes. It is shown in the framework of these equations that, in the generic
      case, the instability development leads to the formation of root singularities at
      the interface in a finite time. The interfacial curvature becomes infinite at
      singular points, while the slope angles remain relatively small. The curvature is
      negative in the vicinity of singularities if the ratio of the permittivities of
      the fluids exceeds the inverse ratio of their densities, and it is positive in
      the opposite case (we consider that the lower fluid is heavier than the upper
      one). In the intermediate case, the interface evolution equations describe the
      formation and sharpening of dimples at the interface. The results obtained are
      applicable for the description of the instability of the interface between two
      magnetic fluids in a vertical magnetic field. 

PMID- 24032932
TI  - Substrate constraint modifies the Rayleigh spectrum of vibrating sessile drops.
AB  - In this work, we study the resonance behavior of mechanically oscillated, sessile
      water drops. By mechanically oscillating sessile drops vertically and within
      prescribed ranges of frequencies and amplitudes, a rich collection of resonance
      modes are observed and their dynamics subsequently investigated. We first present
      our method of identifying each mode uniquely, through association with spherical
      harmonics and according to their geometric patterns. Next, we compare our
      measured resonance frequencies of drops to theoretical predictions using both the
      classical theory of Lord Rayleigh and Lamb for free, oscillating drops, and a
      prediction by Bostwick and Steen that explicitly considers the effect of the
      solid substrate on drop dynamics. Finally, we report observations and analysis of
      drop mode mixing, or the simultaneous coexistence of multiple mode shapes within
      the resonating sessile drop driven by one sinusoidal signal of a single
      frequency. The dynamic response of a deformable liquid drop constrained by the
      substrate it is in contact with is of interest in a number of applications, such
      as drop atomization and ink jet printing, switchable electronically controlled
      capillary adhesion, optical microlens devices, as well as digital microfluidic
      applications where control of droplet motion is induced by means of a
      harmonically driven substrate. 

PMID- 24032933
TI  - Dispersive hydrodynamics in viscous fluid conduits.
AB  - The evolution of the interface separating a conduit of light, viscous fluid
      rising buoyantly through a heavy, more viscous, exterior fluid at small Reynolds
      numbers is governed by the interplay between nonlinearity and dispersion.
      Previous authors have proposed an approximate model equation based on physical
      arguments, but a precise theoretical treatment for this two-fluid system with a
      free boundary is lacking. Here, a derivation of the interfacial equation via a
      multiple scales, perturbation technique is presented. Perturbations about a state
      of vertically uniform, laminar conduit flow are considered in the context of the
      Navier-Stokes equations with appropriate boundary conditions. The ratio of
      interior to exterior viscosities is the small parameter used in the asymptotic
      analysis, which leads systematically to a maximal balance between buoyancy
      driven, nonlinear self-steepening and viscous, interfacial stress induced,
      nonlinear dispersion. This results in a scalar, nonlinear partial differential
      equation describing large amplitude dynamics of the cross-sectional area of the
      intrusive fluid conduit, in agreement with previous derivations. The leading
      order behavior of the two-fluid system is completely characterized in terms of
      the interfacial dynamics. The regime of model validity is characterized and shown
      to agree with previous experimental studies. Viscous fluid conduits provide a
      robust setting for the study of nonlinear, dispersive wave phenomena. 

PMID- 24032934
TI  - Oscillating and star-shaped drops levitated by an airflow.
AB  - We investigate the spontaneous oscillations of drops levitated above an air
      cushion, eventually inducing a breaking of axisymmetry and the appearance of
      "star drops". This is strongly reminiscent of the Leidenfrost stars that are
      observed for drops floating above a hot substrate. The key advantage of this work
      is that we inject the airflow at a constant rate below the drop, thus eliminating
      thermal effects and allowing for a better control of the flow rate. We perform
      experiments with drops of different viscosities and observe stable states,
      oscillations, and chimney instabilities. We find that for a given drop size the
      instability appears above a critical flow rate, where the latter is largest for
      small drops. All these observations are reproduced by numerical simulations,
      where we treat the drop using potential flow and the gas as a viscous lubrication
      layer. Qualitatively, the onset of instability agrees with the experimental
      results, although the typical flow rates are too large by a factor 10. Our
      results demonstrate that thermal effects are not important for the formation of
      star drops and strongly suggest a purely hydrodynamic mechanism for the formation
      of Leidenfrost stars. 

PMID- 24032935
TI  - Anisotropy of flow in stochastically generated porous media.
AB  - Models of porous media are often applied to relatively small systems, which leads
      not only to system-size-dependent results, but also to phenomena that would be
      absent in larger systems. Here we investigate one such finite-size effect:
      anisotropy of the permeability tensor. We show that a nonzero angle between the
      external body force and macroscopic flux vector exists in three-dimensional
      periodic models of sizes commonly used in computer simulations and propose a
      criterion, based on the ratio of the system size to the grain size, for this
      phenomenon to be relevant or negligible. The finite-size anisotropy of the porous
      matrix induces a pressure gradient perpendicular to the axis of a porous duct and
      we analyze how this effect scales with the system and grain sizes. We also
      analyze how the size of the representative elementary volume (REV) for anisotropy
      compares with the REV for permeability. 

PMID- 24032936
TI  - Mechanism of vibration-induced repulsion force on a particle in a viscous fluid
      cell.
AB  - Space platforms such as the Space Shuttle and International Space Station have
      been considered an ideal environment for production of protein and semiconductor
      crystals of superior quality due to the negligible gravity-induced convection.
      Although it was believed that under microgravity environment diffusive mass
      transport would dominate the growth of the crystals, some related experiments
      have not shown satisfactory results possibly due to the movement of the growing
      crystals in fluid cells caused by small vibrations present in the space platforms
      called g-jitter. In ground-based experiments, there have been clear observations
      of attraction and repulsion of a solid particle with respect to a nearby wall of
      the fluid cell due to small vibrations. The present work is a numerical
      investigation on the physical mechanisms responsible for the repulsion force,
      which has been predicted to increase with the cell vibration frequency and
      amplitude, as well as the fluid viscosity. Moreover, the simulations have
      revealed that the repulsion force occurs mostly due to the increased pressure in
      the narrow gap between the particle and the nearest wall. 

PMID- 24032937
TI  - Interaction of bubbles in an inviscid and low-viscosity shear flow.
AB  - The pressure loads on two identical spherical bubbles impulsively introduced in
      an inviscid simple shear flow are calculated. The interaction force due to these
      pressure loads is employed to model the dynamics of air bubbles injected to a low
      viscosity fluid sheared in a Couette device at the first shear flow instability
      where the bubbles are trapped inside the stable Taylor vortex. It was shown that
      the interaction between the bubbles in the primary shear flow drives them away
      from each other. The performed simulations revealed that in an inviscid flow the
      separation distances between equal size bubbles undergo complex periodic motion.
      The presence of low-viscosity results in a qualitative change of the interaction
      pattern: The bubbles either eventually assume an ordered string with equal
      separation distances between all neighbors or some of them collide. The first
      regime is qualitatively similar to the behavior of bubbles at low Reynolds number
      [Prakash et al., Phys. Rev. E 87, 043002 (2013)]. Furthermore, if the Reynolds
      number exceeds some critical value the temporal behavior of the separations
      becomes nonmonotonic and exhibits over- and undershooting of the equilibrium
      separations. The latter effects were observed in the experiments, but are not
      predicted by the low Reynolds number model of the process [Prakash et al., Phys.
      Rev. E 87, 043002 (2013)]. 

PMID- 24032938
TI  - Electric-field-driven contact-line dynamics of two immiscible fluids over
      chemically patterned surfaces in narrow confinements.
AB  - We investigate the contact-line dynamics of two immiscible fluids in a narrow
      fluidic confinement comprising wettability-gradient surfaces, where the bulk
      fluid motion is actuated by an externally applied electric field. We assume that
      the channel walls bear spatially uniform surface potential. Our analysis, based
      on the diffuse interface formalism, reveals that the contact line undergoes stick
      slip motion over the chemical patches and its velocity is a strong function of
      the interfacial electrokinetics. We also show that the tendency of the contact
      line of getting pinned to the selected patches can decrease or increase with its
      progression along the channel, depending on the ratio of the permittivities of
      the two fluids. Finally, we establish the functional dependency of the time taken
      by the contact line to move across the patches (capillary filling time) on the
      combined consequences of interfacial electrochemistry and wettability patterning.

PMID- 24032939
TI  - Mixing and internal dynamics of droplets impacting and coalescing on a solid
      surface.
AB  - The coalescence and mixing of a sessile and an impacting liquid droplet on a
      solid surface are studied experimentally and numerically in terms of lateral
      separation and droplet speed. Two droplet generators are used to produce
      differently colored droplets. Two high-speed imaging systems are used to
      investigate the impact and coalescence of the droplets in color from a side view
      with a simultaneous gray-scale view from below. Millimeter-sized droplets were
      used with dynamical conditions, based on the Reynolds and Weber numbers, relevant
      to microfluidics and commercial inkjet printing. Experimental measurements of
      advancing and receding static contact angles are used to calibrate a contact
      angle hysteresis model within a lattice Boltzmann framework, which is shown to
      capture the observed dynamics qualitatively and the final droplet configuration
      quantitatively. Our results show that no detectable mixing occurs during impact
      and coalescence of similar-sized droplets, but when the sessile droplet is
      sufficiently larger than the impacting droplet vortex ring generation can be
      observed. Finally we show how a gradient of wettability on the substrate can
      potentially enhance mixing. 

PMID- 24032940
TI  - Intermittent flow in yield-stress fluids slows down chaotic mixing.
AB  - We present experimental results of chaotic mixing of Newtonian fluids and yield
      stress fluids using a rod-stirring protocol with a rotating vessel. We show how
      the mixing of yield-stress fluids by chaotic advection is reduced compared to the
      mixing of Newtonian fluids and explain our results, bringing to light the
      relevant mechanisms: the presence of fluid that only flows intermittently, a
      phenomenon enhanced by the yield stress, and the importance of the peripheral
      region. This finding is confirmed via numerical simulations. Anomalously slow
      mixing is observed when the synchronization of different stirring elements leads
      to the repetition of slow stretching for the same fluid particles. 

PMID- 24032941
TI  - Nonlinear pattern formation in thin liquid films under external vibrations.
AB  - We study a thin liquid film with a free surface on a planar horizontal substrate.
      The substrate is subjected to oscillatory accelerations in the normal and/or in
      the horizontal direction(s). The description is based on the longwave
      approximation including inertia effects, which are important due to the large
      velocities imparted by external vibrations. The linearized system is examined
      using the Floquet analysis. Pattern formation in the nonlinear regime is computed
      numerically from the longwave equations for the thickness and the flow rate of
      the fluid in two and in three spatial dimensions. For certain amplitude and
      frequency ranges, combined lateral and normal oscillations can give rise to one
      or more traveling drops, similar to recent experimental findings by Brunet et al.
      [Phys. Rev. Lett. 99, 144501 (2007)]. 

PMID- 24032942
TI  - Rayleigh-Taylor stability boundary at solid-liquid interfaces.
AB  - A previous model for the Rayleigh-Taylor instability [A. R. Piriz, J. J. Lopez
      Cela, and N. A. Tahir, Phys. Rev. E 80, 046305 (2009)] has been extended in order
      to study an interface between an elastic-plastic solid and a Newtonian liquid and
      determine the stability region given by the initial perturbation amplitude xi(0)
      and wavelength lambda. The stability region is found to be enhanced by the effect
      of the liquid viscosity, but it reaches an asymptote for a sufficiently high
      viscosity. In addition, it is also found that the boundary for the transition
      from the elastic to the plastic regime get closer to the stability boundary up to
      both boundaries coincide for a high enough liquid viscosity, thus making the
      onset of plastic flow a sufficient condition for instability.

PMID- 24032943
TI  - Interfacial instability of two superimposed immiscible viscous fluids in a
      vertical Hele-Shaw cell under horizontal periodic oscillations.
AB  - The effect of horizontal periodic oscillations on the interfacial instability of
      two immiscible, viscous fluids of different densities, confined in a vertical
      Hele-Shaw cell, is investigated. An inviscid linear stability analysis of the
      viscous basic flow leads to the periodic Mathieu oscillator describing the
      evolution of interfacial amplitude. We examine mainly the effect of the periodic
      oscillations and the influence of the viscosity on the stability of the
      interface. The results show that a decrease in the viscosity contrast has a
      stabilizing effect on the Kelvin-Helmholtz instability, which is displaced
      towards the long-wave region. The effects of other parameters such as the
      frequency number and the Weber number are also examined. 

PMID- 24032944
TI  - Hydromagnetic thin film flow: linear stability.
AB  - This paper deals with the long wave instability of an electroconductor fluid
      film, flowing down an inclined plane at small to moderate Reynolds numbers, under
      the action of electromagnetic fields. A coherent second order long wave model and
      two simplified versions of it, referred to as first and second reduced models
      (FRM and SRM), are proposed to describe the nonlinear behavior of the flow. The
      modeling procedure consists of a combination of the lubrication theory and the
      weighted residual approach using an appropriate projection basis. A suitable
      choice of weighting functions allows a significant reduction of the dimension of
      the problem. The full model is naturally unique, i.e., independent of the
      particular form of the trial functions. The linear stability of the problem is
      investigated, and the influence of electromagnetic field on the flow stability is
      analyzed. Two cases are considered: the applied magnetic field is either normal
      or parallel to the fluid flow direction, while the electric field is transversal.
      The numerical solution of the Orr-Sommerfeld (OS) eigenvalue problem and those of
      the depth averaging model are used to assess the accuracy of the reduced models.
      It is found that the current models have the advantage of the Benney-like model,
      which is known to asymptote the exact solution near criticality. Moreover, far
      from the instability threshold, the current reduced models continue to follow the
      OS solution up to moderate Reynolds numbers, while the averaging model diverges
      rapidly. The model SRM gives better results than FRM beyond sufficiently high
      Reynolds numbers. 

PMID- 24032945
TI  - Interaction between a pair of particles settling in a stratified fluid.
AB  - The anisotropic structure of fluidized suspensions is governed by their
      microstructures which are in turn determined by the dynamics of particle pair
      interactions. Here, we present a numerical simulation of particle interaction in
      linearly stratified fluids. It is shown that unlike homogeneous fluids,
      stratification results in the attraction of particles settling abreast. The
      attraction between the particles is characterized by the combined effects of
      buoyancy, inertia, and diffusion. The interaction of the particles settling in
      tandem can be fundamentally altered due to the presence of the background density
      gradients and the drafting-kissing-tumbling behavior in a homogeneous fluid can
      be replaced by drafting-kissing-separation or drafting-separation phenomenon
      depending on the strength of the stratification. In the case of weak
      stratification, drafting-kissing-tumbling occurs, however, a prolonged kissing
      time is observed and the rate of change of the orientation of particles is
      reduced. It is shown that the formation of the buoyancy-induced vortical
      structures and the generation of stratified jets behind the particles are the
      fundamental mechanisms in governing the dynamics of the particle pair interaction
      in stratified fluids. 

PMID- 24032946
TI  - Simulating the dynamics of complex plasmas.
AB  - Complex plasmas are low-temperature plasmas that contain micrometer-size
      particles in addition to the neutral gas particles and the ions and electrons
      that make up the plasma. The microparticles interact strongly and display a
      wealth of collective effects. Here we report on linked numerical simulations that
      reproduce many of the experimental results of complex plasmas. We model a
      capacitively coupled plasma with a fluid code written for the commercial package
      comsol. The output of this model is used to calculate forces on microparticles.
      The microparticles are modeled using the molecular dynamics package lammps, which
      we extended to include the forces from the plasma. Using this method, we are able
      to reproduce void formation, the separation of particles of different sizes into
      layers, lane formation, vortex formation, and other effects. 

PMID- 24032947
TI  - Nonstationary magnetosonic wave dynamics in plasmas exhibiting collapse.
AB  - In a Lagrangian fluid approach, an explicit method has been presented previously
      to obtain an exact nonstationary magnetosonic-type wave solution in compressible
      magnetized plasmas of arbitrary resistivity showing competition among
      hydrodynamic convection, magnetic field diffusion, and dispersion [Chakrabarti et
      al., Phys. Rev. Lett. 106, 145003 (2011)]. The purpose of the present work is
      twofold: it serves (i) to describe the physical and mathematical background of
      the involved magnetosonic wave dynamics in more detail, as proposed by our
      original Letter, and (ii) to present an alternative approach, which utilizes the
      Lagrangian mass variable as a new spatial coordinate [Schamel, Phys. Rep. 392,
      279 (2004)]. The obtained exact nonlinear wave solutions confirm the correctness
      of our previous results, indicating a collapse of the magnetic field irrespective
      of the presence of dispersion and resistivity. The mean plasma density, on the
      other hand, is less singular, showing collapse only when dispersive effects are
      negligible. These results may contribute to our understanding of the generation
      of strongly localized magnetic fields (and currents) in plasmas, and they are
      expected to be of special importance in the astrophysical context of magnetic
      star formation. 

PMID- 24032948
TI  - Re-examining the Cairns-Tsallis model for ion acoustic solitons.
AB  - Recently, a hybrid distribution function [Tribeche et al., Phys. Rev. E 85,
      037401 (2012)] was proposed to describe a plasma species with an enhanced
      superthermal component. This combines a Cairns-type "nonthermal" form with the
      Tsallis theory for nonextensive thermodynamics. Using this alternative model, the
      propagation of arbitrary amplitude ion acoustic solitary waves in a two-component
      plasma is investigated. From a careful study of the distribution function it is
      found that the model itself is valid only for a very restricted range in the q
      nonextensive parameter and the nonthermality parameter, alpha. Solitary waves,
      the amplitude and nature of which depend sensitively on both q and alpha, can
      exist within a narrow range of allowable Mach numbers. Both positive and negative
      potential structures are found, and coexistence may occur. 

PMID- 24032949
TI  - Discharging of dust particles in the afterglow of plasma with large dust density.
AB  - The discharging of dust particles in the afterglow of plasma with large dust
      density is studied. We used measured electron and metastable dependencies to
      calculate the rate describing collection of electrons by dust particles by
      solving the electron balance equation. This rate is compared with the rate
      calculated using the orbital motion limited (OML) theory. It is found that the
      OML theory may not be applied for description of dust charging at large afterglow
      times, and the energetic electrons generated in metastable-metastable collisions
      significantly affect charging of dust particles. The time dependence for dust
      charge is calculated by two different approaches: first, the "standard" approach
      is used, which assumes that ion and electron fluxes to the dust particles are
      different in the afterglow. Second, the dust charge is calculated by assuming
      that desorption of electrons from dust particles is very fast. Both approaches
      gave similar results for dust charging. In addition, the effects of secondary
      emission due to ion-dust and metastable-dust collisions on dust discharging are
      investigated. The main source of dust charging in the late afterglow of plasma
      with large dust density are the energetic electrons generated in Ar(m) metastable
      metastable collisions.

PMID- 24032950
TI  - Self-modulation of nonlinear Alfven waves in a strongly magnetized relativistic
      electron-positron plasma.
AB  - We study the self-modulation of a circularly polarized Alfven wave in a strongly
      magnetized relativistic electron-positron plasma with finite temperature. This
      nonlinear wave corresponds to an exact solution of the equations, with a
      dispersion relation that has two branches. For a large magnetic field, the Alfven
      branch has two different zones, which we call the normal dispersion zone (where
      domega/dk>0) and the anomalous dispersion zone (where domega/dk<0). A nonlinear
      Schrodinger equation is derived in the normal dispersion zone of the Alfven wave,
      where the wave envelope can evolve as a periodic wave train or as a solitary
      wave, depending on the initial condition. The maximum growth rate of the
      modulational instability decreases as the temperature is increased. We also study
      the Alfven wave propagation in the anomalous dispersion zone, where a nonlinear
      wave equation is obtained. However, in this zone the wave envelope can evolve
      only as a periodic wave train. 

PMID- 24032951
TI  - Ultrasharp-front laser pulses generated by energetic-electron flux triggering of
      laser propagation in overdense plasmas.
AB  - This paper reports that an initially opaque plasma foil, irradiated by a laser
      pulse with intensity below the self-induced transparency (SIT) threshold, will
      become transparent, if a flux of energetic electrons is present. Based on this
      phenomenon, named flux-induced transparency (FIT), an approach to obtaining
      ultrasharp-front laser pulses is proposed. With the presence of an energetic
      electron flux generated by a p-polarized laser irradiating an overdense plasma
      foil from the rear side, the propagation of an s-polarized laser irradiating the
      front surface of the foil can be manipulated. The transmitted s-polarized laser
      pulse has an ultrasharp front which rises by three orders of magnitude within a
      few laser cycles. The profile of the transmitted pulse is tunable by controlling
      the time at which the energetic-electron flux arrives at the front surface. 

PMID- 24032952
TI  - Kinetic theory of fully degenerate electrons in the long scale limit.
AB  - The kinetic theory of fully degenerate electrons in a weakly coupled plasma is
      considered. We derive an evolution equation for a generalized Fermi surface that
      also depends on the electron spin state. The equation allows for the study of
      weakly nonlinear modifications of the Fermi surface within perturbation theory.
      We apply the theory to Landau damping of ion-acoustic waves. The transition to
      the nonlinear stage and the nonlinear modification of the Fermi surface are
      investigated. 

PMID- 24032953
TI  - Stability of three-dimensional dust acoustic waves in a dusty plasma with two
      opposite polarity dust species including dust size distribution.
AB  - Propagation of dust acoustic waves (DAWs) with the effect of power law dust size
      distribution (DSD) in a magnetized dusty plasma with opposite polarity dust is
      studied. Using a reductive perturbation method, a Zakharov-Kuznetsov equation
      appropriate for describing three-dimensional DAWs is derived. The compressive and
      rarefactive solitons are possible in the present model. Due to the DSD effect, a
      soliton with a smaller amplitude and width and a larger velocity is observed. The
      stability criterion for obliquely propagating DAWs in such plasma using small-k
      expansion method is investigated. The growth rate of instability is derived and
      analyzed under the effect of power law DSD. It is found that the growth rate of
      instability is strongly affected by the power law DSD. The relevance of these
      findings to space plasma phenomena is briefly discussed. 

PMID- 24032954
TI  - Optical signatures of the charge of a dielectric particle in a plasma.
AB  - With an eye on dust particles immersed into an ionized gas, we study the effect
      of a negative charge on the scattering of light by a dielectric particle with a
      strong transverse optical phonon resonance in the dielectric constant. Surplus
      electrons alter the scattering behavior of the particle by their phonon-limited
      conductivity in the surface layer (negative electron affinity) or in the bulk of
      the particle (positive electron affinity). We identify a charge-dependent
      increase of the extinction efficiency for low frequencies, a shift of the
      extinction resonance above the transverse optical phonon frequency, and a rapid
      variation of the polarization angles over this resonance. These effects could be
      used for noninvasive optical measurements of the charge of the particle. 

PMID- 24032955
TI  - Equilibrium probability distribution of a conductive sphere's floating charge in
      a collisionless, drifting Maxwellian plasma.
AB  - A dust grain in a plasma has a fluctuating electric charge, and past work
      concludes that spherical grains in a stationary, collisionless plasma have an
      essentially Gaussian charge probability distribution. This paper extends that
      work to flowing plasmas and arbitrarily large spheres, deriving analytic charge
      probability distributions up to normalizing constants. We find that these
      distributions also have good Gaussian approximations, with analytic expressions
      for their mean and variance. 

PMID- 24032956
TI  - Coherent transmission of an ultrasonic shock wave through a multiple scattering
      medium.
AB  - We report measurements of the transmitted coherent (ensemble-averaged) wave
      resulting from the interaction of an ultrasonic shock wave with a two-dimensional
      random medium. Despite multiple scattering, the coherent waveform clearly shows
      the steepening that is typical of nonlinear harmonic generation. This is taken
      advantage of to measure the elastic mean free path and group velocity over a
      broad frequency range (2-15 MHz) in only one experiment. Experimental results are
      found to be in good agreement with a linear theoretical model taking into account
      spatial correlations between scatterers. These results show that nonlinearity and
      multiple scattering are both present, yet uncoupled. 

PMID- 24032957
TI  - Twisted rogue-wave pairs in the Sasa-Satsuma equation.
AB  - Exact explicit rogue wave solutions of the Sasa-Satsuma equation are obtained by
      use of a Darboux transformation. In addition to the double-peak structure and an
      analog of the Peregrine soliton, the rogue wave can exhibit an intriguing twisted
      rogue-wave pair that involves four well-defined zero-amplitude points. This
      exotic structure may enrich our understanding on the nature of rogue waves. 

PMID- 24032958
TI  - Effects of parity-time symmetry in nonlinear Klein-Gordon models and their
      stationary kinks.
AB  - In this work, we introduce some basic principles of PT-symmetric Klein-Gordon
      nonlinear field theories. By formulating a particular antisymmetric gain and loss
      profile, we illustrate that the stationary states of the model do not change.
      However, the stability critically depends on the gain and loss profile. For a
      symmetrically placed solitary wave (in either the continuum model or a discrete
      analog of the nonlinear Klein-Gordon type), there is no effect on the steady
      state spectrum. However, for asymmetrically placed solutions, there exists a
      measurable effect of which a perturbative mathematical characterization is
      offered. It is generally found that asymmetry towards the lossy side leads
      towards stability, while towards the gain side produces instability. Furthermore,
      a host of finite size effects, which disappear in the infinite domain limit, are
      illustrated in connection to the continuous spectrum of the problem. 

PMID- 24032959
TI  - Parameter retrieval of chiral metamaterials based on the state-space approach.
AB  - This paper deals with the introduction of an approach for the electromagnetic
      characterization of homogeneous chiral layers. The proposed method is based on
      the state-space approach and properties of a 4*4 state transition matrix. Based
      on this, first, the forward problem analysis through the state-space method is
      reviewed and properties of the state transition matrix of a chiral layer are
      presented and proved as two theorems. The formulation of a proposed
      electromagnetic characterization method is then presented. In this method,
      scattering data for a linearly polarized plane wave incident normally on a
      homogeneous chiral slab are combined with properties of a state transition matrix
      and provide a powerful characterization method. The main difference with respect
      to other well-established retrieval procedures based on the use of the scattering
      parameters relies on the direct computation of the transfer matrix of the slab as
      opposed to the conventional calculation of the propagation constant and impedance
      of the modes supported by the medium. The proposed approach allows avoiding
      nonlinearity of the problem but requires getting enough equations to fulfill the
      task which was provided by considering some properties of the state transition
      matrix. To demonstrate the applicability and validity of the method, the
      constitutive parameters of two well-known dispersive chiral metamaterial
      structures at microwave frequencies are retrieved. The results show that the
      proposed method is robust and reliable. 

PMID- 24032960
TI  - Dynamic implicit-solvent coarse-grained models of lipid bilayer membranes:
      fluctuating hydrodynamics thermostat.
AB  - We introduce a thermostat based on fluctuating hydrodynamics for dynamic
      simulations of implicit-solvent coarse-grained models of lipid bilayer membranes.
      We show our fluctuating hydrodynamics approach captures interesting correlations
      in the dynamics of lipid bilayer membranes that are missing in simulations
      performed using standard Langevin dynamics. Our momentum conserving thermostat
      accounts for solvent-mediated momentum transfer by coupling coarse-grained
      degrees of freedom to stochastic continuum fields that account for both the
      solvent hydrodynamics and thermal fluctuations. We present both a general
      framework and specific methods to couple the particle and continuum degrees of
      freedom in a manner consistent with statistical mechanics and amenable to
      efficient computational simulation. For self-assembled vesicles, we study the
      diffusivity of lipids and their spatial correlations. We find the hydrodynamic
      coupling yields within the bilayer interesting correlations between diffusing
      lipids that manifest as a vortex-like structure similar to those observed in
      explicit-solvent simulations. We expect the introduced fluctuating hydrodynamics
      methods to provide a way to extend implicit-solvent models for use in a wide
      variety of dynamic studies. 

PMID- 24032961
TI  - Determination of bed elevation in the enhanced lattice Boltzmann method for the
      shallow-water equations.
AB  - The bed slope in the shallow-water equations reflects the bed topography. It is
      not a flow variable and cannot be determined in the solution to the flow
      equations. An immovable nonflat bed affects a flow as a force term, but the flow
      has no effect on it. Only when the bed term is correctly represented in a
      numerical method can it generate an accurate solution. In the enhanced lattice
      Boltzmann method for the shallow-water equations (eLABSWE), using an individual
      Chapman-Enskog analysis, it is found that such a correct representation can be
      achieved by retaining C(alpha)=2lambda(alpha), in which C(alpha) is the
      coefficient for bed elevation in the lattice Boltzmann equation and lambda(alpha)
      is that for the water depth in the local equilibrium distribution function. The
      finding has been validated through simulations of a water at rest in a dish
      shaped lake, a wind-induced shallow flow in the same lake, and a steady flow over
      a two-dimensional bed hump.

PMID- 24032962
TI  - Dynamics of the sub-Ohmic spin-boson model: a comparison of three numerical
      approaches.
AB  - Dynamics of the sub-Ohmic spin-boson model is examined using three numerical
      approaches, namely the Dirac-Frenkel time-dependent variation with the Davydov
      D(1) ansatz, the adaptive time-dependent density matrix renormalization group
      method within the representation of orthogonal polynomials, and a perturbative
      approach based on a unitary transformation. In order to probe the validity
      regimes of the three approaches, we study the dynamics of a qubit coupled to a
      bosonic bath with and without a local field. Comparison of the up-state
      population evolution shows that the three approaches are in agreement in the weak
      coupling regime but exhibit marked differences when the coupling strength is
      large. The Davydov D(1) ansatz and the time-dependent density matrix
      renormalization group can both be reliably employed in the weak-coupling regime,
      while the former is also valid in the strong-coupling regime as judged by how
      faithfully the trial state follows the Schrodinger equation. We further explore
      the bipartite entanglement dynamics between two qubits coupled with individual
      bosonic baths which reveals entanglement sudden death and revival.

PMID- 24032963
TI  - Isotropic model for cluster growth on a regular lattice.
AB  - There exists a plethora of mathematical models for cluster growth and/or
      aggregation on regular lattices. Almost all suffer from inherent anisotropy
      caused by the regular lattice upon which they are grown. We analyze the little
      known model for stochastic cluster growth on a regular lattice first introduced
      by Ferreira Jr. and Alves [J. Stat. Mech. Theo. & Exp. (2006) P11007], which
      produces circular clusters with no discernible anisotropy. We demonstrate that
      even in the noise-reduced limit the clusters remain circular. We adapt the model
      by introducing a specific rearrangement algorithm so that, rather than adding
      elements to the cluster from the outside (corresponding to apical growth), our
      model uses mitosis-like cell splitting events to increase the cluster size. We
      analyze the surface scaling properties of our model and compare it to the
      behavior of more traditional models. In "1+1" dimensions we discover and explore
      a new, nonmonotonic surface thickness scaling relationship which differs
      significantly from the Family-Vicsek scaling relationship. This suggests that,
      for models whose clusters do not grow through particle additions which are solely
      dependent on surface considerations, the traditional classification into
      "universality classes" may not be appropriate. 

PMID- 24032964
TI  - Linking hydrophobicity and hydrodynamics by the hybrid fluctuating hydrodynamics
      and molecular dynamics methodologies.
AB  - The development of a hybrid fluctuating hydrodynamics (FHD) and molecular
      dynamics (MD) simulation method that combines the molecular dynamics of moving
      particles with the fluctuating hydrodynamics of solvent fields on Eulerian grid
      cells is presented. This method allows resolution of solute-solvent interfaces
      and realization of excluded volumes of particles in the presence of hydrodynamic
      coupling. With these capabilities, we show that the ubiquitous forces mediated by
      the solvent, hydrophobicity and hydrodynamics, can be linked in a mesoscopic
      simulation. The strategies we devise to overcome the numerical issues of mixing
      variables in the Eulerian and Lagrangian coordinate systems, i.e., using a pair
      of auxiliary fluids to realize the excluded volumes of particles and assigning
      collocating gridding systems on solutes to interface with solvent fields, are
      also presented. Simulation results show that the hybrid FHD and MD method can
      reproduce the solvation free energies and scaling laws of particles dynamics for
      hydrophobes of different sizes. The collapse of two hydrophobic particles was
      also simulated to illustrate that the hybrid FHD and MD method has the potential
      to be generally applied to study nanoscale self-assembly and dynamics-structure
      function relationships of biomolecules. 

PMID- 24032965
TI  - Phase-field crystal model with a vapor phase.
AB  - Phase-field crystal (PFC) models are able to resolve atomic length scale features
      of materials during temporal evolution over diffusive time scales. Traditional
      PFC models contain solid and liquid phases, however many important materials
      processing phenomena involve a vapor phase as well. In this work, we add a vapor
      phase to an existing PFC model and show realistic interfacial phenomena near the
      triple point temperature. For example, the PFC model exhibits density
      oscillations at liquid-vapor interfaces that compare favorably to data available
      for interfaces in metallic systems from both experiment and molecular-dynamics
      simulations. We also quantify the anisotropic solid-vapor surface energy for a
      two-dimensional PFC hexagonal crystal and find well-defined step energies from
      measurements on the faceted interfaces. Additionally, the strain field beneath a
      stepped interface is characterized and shown to qualitatively reproduce
      predictions from continuum models, simulations, and experimental data. Finally,
      we examine the dynamic case of step-flow growth of a crystal into a
      supersaturated vapor phase. The ability to model such a wide range of surface and
      bulk defects makes this PFC model a useful tool to study processing techniques
      such as chemical vapor deposition or vapor-liquid-solid growth of nanowires. 

PMID- 24032966
TI  - No-go theorem for ergodicity and an Einstein relation.
AB  - We provide a simple no-go theorem for ergodicity and the generalized Einstein
      relation for anomalous diffusion processes. The theorem states that either
      ergodicity in the sense of equal time and ensemble averaged mean squared
      displacements (MSD) is broken, and/or the generalized Einstein relation for time
      averaged diffusivity and mobility is invalid, which is in complete contrast to
      normal diffusion processes. We also give a general relation for the time averages
      of drift and MSD for ergodic (in the MSD sense) anomalous diffusion processes,
      showing that the ratio of these quantities depends on the measurement time. The
      Levy walk model is used to exemplify the no-go theorem. 

PMID- 24032967
TI  - Nonstandard scaling law of fluctuations in finite-size systems of globally
      coupled oscillators.
AB  - Universal scaling laws form one of the central issues in physics. A nonstandard
      scaling law or a breakdown of a standard scaling law, on the other hand, can
      often lead to the finding of a new universality class in physical systems.
      Recently, we found that a statistical quantity related to fluctuations follows a
      nonstandard scaling law with respect to the system size in a synchronized state
      of globally coupled nonidentical phase oscillators [I. Nishikawa et al., Chaos
      22, 013133 (2012)]. However, it is still unclear how widely this nonstandard
      scaling law is observed. In the present paper, we discuss the conditions required
      for the unusual scaling law in globally coupled oscillator systems and validate
      the conditions by numerical simulations of several different models. 

PMID- 24032968
TI  - Lehmann effects and rotatoelectricity in liquid crystalline systems made of
      achiral molecules.
AB  - We discuss Lehmann effects and rotato-electricity for liquid crystalline phases
      made of achiral molecules. We point out that for static and dynamic Lehmann
      effects to exist, it is not necessary to have chiral molecules provided the
      overall structure has macroscopic chirality. This question is of direct relevance
      for liquid crystalline phases formed by bent-core molecules provided they have a
      sufficiently low symmetry. This includes systems which break parity symmetry and
      have overall C(2) or C(1) symmetry. We point out that for liquid crystalline gels
      and elastomers one should be able to observe rotato-electricity for systems with
      macroscopic chirality. Rotatoelectricity is associated with the relative
      rotations between two subsystems, namely, between the network and the director,
      in an external electric field. Candidates include gels and even monolayers
      prepared from bent-core molecules with sufficiently low symmetry.

PMID- 24032969
TI  - Critical avalanches and subsampling in map-based neural networks coupled with
      noisy synapses.
AB  - Many different kinds of noise are experimentally observed in the brain. Among
      them, we study a model of noisy chemical synapse and obtain critical avalanches
      for the spatiotemporal activity of the neural network. Neurons and synapses are
      modeled by dynamical maps. We discuss the relevant neuronal and synaptic
      properties to achieve the critical state. We verify that networks of functionally
      excitable neurons with fast synapses present power-law avalanches, due to rebound
      spiking dynamics. We also discuss the measuring of neuronal avalanches by
      subsampling our data, shedding light on the experimental search for self
      organized criticality in neural networks. 

PMID- 24032970
TI  - Generalized Achlioptas process for the delay of criticality in the percolation
      process.
AB  - We extend the Achlioptas model for the delay of criticality in the percolation
      problem. Instead of having a completely random connectivity pattern, we
      generalize the idea of the two-site probe in the Achlioptas model for connecting
      smaller clusters, by introducing two models: the first one by allowing any number
      k of probe sites to be investigated, k being a parameter, and the second one
      independent of any specific number of probe sites, but with a probabilistic
      character which depends on the size of the resulting clusters. We find
      numerically the complete spectrum of critical points and our results indicate
      that the value of the critical point behaves linearly with k after the value of k
      = 3. The range k = 2-3 is not linear but parabolic. The more general model of
      generating clusters with probability inversely proportional to the size of the
      resulting cluster produces a critical point which is equivalent to the value of k
      being in the range k = 5-7. 

PMID- 24032971
TI  - Engagement in the electoral processes: scaling laws and the role of political
      positions.
AB  - We report on a statistical analysis of the engagement in the electoral processes
      of all Brazilian cities by considering the number of party memberships and the
      number of candidates for mayor and councillor. By investigating the relationships
      between the number of party members and the population of voters, we have found
      that the functional forms of these relationships are well described by sublinear
      power laws (allometric scaling) surrounded by a multiplicative log-normal noise.
      We have observed that this pattern is quite similar to those we previously
      reported for the relationships between the number of candidates (mayor and
      councillor) and population of voters [Europhys. Lett. 96, 48001 (2011)],
      suggesting that similar universal laws may be ruling the engagement in the
      electoral processes. We also note that the power-law exponents display a clear
      hierarchy, where the more influential is the political position the smaller is
      the value of the exponent. We have also investigated the probability
      distributions of the number of candidates (mayor and councillor), party
      memberships, and voters. The results indicate that the most influential positions
      are characterized by distributions with very short tails, while less influential
      positions display an intermediate power-law decay before showing an exponential
      like cutoff. We discuss the possibility that, in addition to the political power
      of the position, limitations in the number of available seats can also be
      connected with this changing of behavior. We further believe that our empirical
      findings point out to an under-representation effect, where the larger the city
      is, the larger are the obstacles for more individuals to become directly engaged
      in the electoral process. 

PMID- 24032972
TI  - Limiting phase trajectories and emergence of autoresonance in nonlinear
      oscillators.
AB  - Existence of stable autoresonance (AR) with continuously growing energy is
      directly connected with the inherent property of nonlinear systems to remain in
      resonance when the driving frequency varies in time. However, the physical
      mechanism underlying the transformation of bounded oscillations into AR remains
      unclear. As this paper demonstrates, the emergence of AR from stable bounded
      oscillations is basically analogous to the transition from quasilinear to
      nonlinear oscillations in the time-invariant oscillator driven by an external
      harmonic excitation with constant frequency, and AR can occur as a result of the
      loss of stability of the so-called limiting phase trajectory. We obtain the
      parametric threshold, which determines the transition from bounded oscillations
      to AR in the time-dependent system. The accuracy of the obtained approximations
      is confirmed by numerical simulations. 

PMID- 24032973
TI  - Large-amplitude oscillations in the rectangular Fermi accelerator.
AB  - Exponential energy growth in a rectangular billiard with an oscillating bar has
      been clearly demonstrated earlier. Using the log-normal approximation, analytical
      estimates for the energy growth rate have also been provided. However, these
      analytical estimates are valid only when the amplitude of oscillation of the bar
      is small. In this paper, for larger oscillation amplitude, the log-normal
      approximation is numerically shown to be invalid and analytical estimates are
      obtained for the true energy growth rate in the case of very large particle
      velocities or small bar length. It is also shown that when everything else
      remains constant, the length of the bar which gives rise to maximum energy growth
      rate decreases as the oscillation amplitude increases and the true value of this
      maximizing length is also smaller than what is predicted by the log-normal
      approximation. Thus, the rectangular Fermi accelerator forms a very good example
      of a contemporary research problem where the limitations of the log-normal
      approximation can be easily appreciated. 

PMID- 24032974
TI  - Bright solitons from the nonpolynomial Schrodinger equation with inhomogeneous
      defocusing nonlinearities.
AB  - Extending the recent work on models with spatially nonuniform nonlinearities, we
      study bright solitons generated by the nonpolynomial self-defocusing (SDF)
      nonlinearity in the framework of the one-dimensional (1D) Munoz-Mateo-Delgado (MM
      D) equation (the 1D reduction of the Gross-Pitaevskii equation with the SDF
      nonlinearity), with the local strength of the nonlinearity growing at |x|
      >infinity faster than |x|. We produce numerical solutions and analytical ones,
      obtained by means of the Thomas-Fermi approximation, for nodeless ground states
      and for excited modes with one, two, three and four nodes, in two versions of the
      model, with steep (exponential) and mild (algebraic) nonlinear-modulation
      profiles. In both cases, the ground states and the single-node ones are
      completely stable, while the stability of the higher-order modes depends on their
      norm (in the case of the algebraic modulation, they are fully unstable). Unstable
      states spontaneously evolve into their stable lower-order counterparts. 

PMID- 24032975
TI  - Comment on "Subgraph centrality in complex networks".
AB  - We disprove a conjecture of Estrada and Rodriguez-Velazquez [Phys. Rev. E 71,
      056103 (2005)] that if a graph has identical subgraph centrality for all nodes,
      then the closeness and betweenness centralities are also identical for all nodes.

PMID- 24032976
TI  - Comment on "Proposal of a critical test of the Navier-Stokes-Fourier paradigm for
      compressible fluid continua".
AB  - Recently, a critical test of the Navier-Stokes-Fourier equations for compressible
      fluid continua was proposed [H. Brenner, Phys. Rev. E 87, 013014 (2013)]. It was
      shown that the equations of bivelocity hydrodynamics imply that a compressible
      fluid in an isolated rotating circular cylinder attains a nonequilibrium steady
      state with a nonuniform temperature increasing radially with distance from the
      axis. We demonstrate that statistical mechanical arguments, involving Hamiltonian
      dynamics and ergodicity due to irregularity of the wall, lead instead to a
      thermal equilibrium state with uniform temperature. This is the situation to be
      expected in experiment. 

PMID- 24032977
TI  - Bendamustine efficacy in Hodgkin lymphoma patients relapsed/refractory to
      brentuximab vedotin.

PMID- 24032978
TI  - Lynch syndrome mutations shared by the Baltic States and Poland.

PMID- 24032979
TI  - Distinctive features of the D101N and D101G variants of superoxide dismutase 1;
      two mutations that produce rapidly progressing motor neuron disease.
AB  - Mutations in superoxide dismutase 1 (SOD1) associated with familial amyotrophic
      lateral sclerosis induce misfolding and aggregation of the protein with the
      inherent propensity of mutant SOD1 to aggregate generally correlating, with a few
      exceptions, to the duration of illness in patients with the same mutation. One
      notable exception was the D101N variant, which has been described as wild-type
      like. The D101N mutation is associated with rapidly progressing motor neuron
      degeneration but shows a low propensity to aggregate. By assaying the kinetics of
      aggregation in a well-characterized cultured cell model, we show that the D101N
      mutant is slower to initiate aggregation than the D101G mutant. In this cell
      system of protein over-expression, both mutants were equally less able to acquire
      Zn than WT SOD1. In addition, both of these mutants were equivalently less able
      to fold into the trypsin-resistant conformation that characterizes WT SOD1. A
      second major difference between the two mutants was that the D101N variant more
      efficiently formed a normal intramolecular disulfide bond. Overall, our findings
      demonstrate that the D101N and D101G variants exhibit clearly distinctive
      features, including a different rate of aggregation, and yet both are associated
      with rapidly progressing disease. We sought to better characterize the
      biochemical features of two SOD1 mutants associated with rapidly progressing
      disease, the D101G and wild-type like D101N mutants. We observed using our cell
      model that that although similarities were observed when comparing the ability to
      bind metals and resist trypsin digestion, these mutants differed in their ability
      to initiate aggregation and to form the normal intramolecular disulfide bond. We
      conclude that these mutants exhibit distinct properties despite producing similar
      disease phenotypes in patients.

PMID- 24032980
TI  - A synthetic framework for modeling the genetic basis of phenotypic plasticity and
      its costs.
AB  - The phenotype of an individual is controlled not only by its genes, but also by
      the environment in which it grows. A growing body of evidence shows that the
      extent to which phenotypic changes are driven by the environment, known as
      phenotypic plasticity, is also under genetic control, but an overall picture of
      genetic variation for phenotypic plasticity remains elusive. Here, we develop a
      model for mapping quantitative trait loci (QTLs) that regulate environment
      induced plastic response. This model enables geneticists to test whether there
      exist actual QTLs that determine phenotypic plasticity and, if there are, further
      test how plasticity QTLs control the costs of plastic response by dissecting the
      genetic correlation of phenotypic plasticity and trait value. The model was used
      to analyze real data for grain yield of winter wheat (Triticum aestivum), leading
      to the detection of pleiotropic QTLs and epistatic QTLs that affect phenotypic
      plasticity and its cost in this crop. 

PMID- 24032981
TI  - IspC as target for antiinfective drug discovery: synthesis, enantiomeric
      separation, and structural biology of fosmidomycin thia isosters.
AB  - The emergence and spread of multidrug-resistant pathogens are widely believed to
      endanger human health. New drug targets and lead compounds exempt from cross
      resistance with existing drugs are urgently needed. We report on the synthesis
      and properties of "reverse" thia analogs of fosmidomycin, which inhibit the first
      committed enzyme of a metabolic pathway that is essential for the causative
      agents of tuberculosis and malaria but is absent in the human host. Notably, IspC
      displays a high level of enantioselectivity for an alpha-substituted fosmidomycin
      derivative. 

PMID- 24032983
TI  - Behavior patterns of physical therapists in screening for loss of protective
      sensation in clients with diabetes.
AB  - Peripheral neuropathy is a common consequence of diabetes that often results in
      loss of protective sensation. Early identification of this loss is critical to
      minimize secondary complications. The authors' purpose was to assess the behavior
      patterns of physical therapists as to their opinions and behaviors related to
      sensory testing for individuals with diabetes. A questionnaire was sent to
      physical therapists across the United States with the following results: a high
      level of agreement concerning the benefits of sensory testing, but with a far
      less agreement as to the actual performance of sensory testing by those same
      physical therapists.

PMID- 24032984
TI  - Simplifying the negotiating process with physicians: critical elements in
      negotiating from private practice to employed physician.
AB  - The authors attempt to simplify the key elements to the process of negotiating
      successfully with private physicians. From their experience, the business
      elements that have resulted in the most discussion center on the compensation
      including the incentive plan. Secondarily, how the issue of malpractice is
      handled will also consume a fair amount of time. What the authors have also
      learned is that the intangible issues can often be the reason for an unexpectedly
      large amount of discussion and therefore add time to the negotiation process. To
      assist with this process, they have derived a negotiation checklist, which seeks
      to help hospital leaders and administrators set the proper framework to ensure
      successful negotiation conversations. More importantly, being organized and
      recognizing these broad issues upfront and remaining transparent throughout the
      process will help to ensure a successful negotiation.

PMID- 24032982
TI  - Subclinical early posttraumatic seizures detected by continuous EEG monitoring in
      a consecutive pediatric cohort.
AB  - PURPOSE: Traumatic brain injury (TBI) is an important cause of morbidity and
      mortality in children, and early posttraumatic seizures (EPTS) are a contributing
      factor to ongoing acute damage. Continuous video-EEG monitoring (cEEG) was
      utilized to assess the burden of clinical and electrographic EPTS. METHODS:
      Eighty-seven consecutive, unselected (mild - severe), acute TBI patients
      requiring pediatric intensive care unit (PICU) admission at two academic centers
      were monitored prospectively with cEEG per established clinical TBI protocols.
      Clinical and subclinical seizures and status epilepticus (SE, clinical and
      subclinical) were assessed for their relation to clinical risk factors and short
      term outcome measures. KEY FINDINGS: Of all patients, 42.5% (37/87) had seizures.
      Younger age (p = 0.002) and injury mechanism (abusive head trauma - AHT, p <
      0.001) were significant risk factors. Subclinical seizures occurred in 16.1%
      (14/87), while 6.9% (6/87) had only subclinical seizures. Risk factors for
      subclinical seizures included younger age (p < 0.001), AHT (p < 0.001), and
      intraaxial bleed (p < 0.001). SE occurred in 18.4% (16/87) with risk factors
      including younger age (p < 0.001), AHT (p < 0.001), and intraaxial bleed (p =
      0.002). Subclinical SE was detected in 13.8% (12/87) with significant risk
      factors including younger age (p < 0.001), AHT (p = 0.001), and intraaxial bleed
      (p = 0.004). Subclinical seizures were associated with lower discharge King's
      Outcome Scale for Childhood Head Injury (KOSCHI) score (p = 0.002). SE and
      subclinical SE were associated with increased hospital length of stay (p = 0.017
      and p = 0.041, respectively) and lower hospital discharge KOSCHI (p = 0.007 and p
      = 0.040, respectively). SIGNIFICANCE: cEEG monitoring significantly improves
      detection of seizures/SE and is the only way to detect subclinical seizures/SE.
      cEEG may be indicated after pediatric TBI, particularly in younger children, AHT
      cases, and those with intraaxial blood on computerized tomography (CT).

PMID- 24032985
TI  - Pharmacists: an important resource to improve core measure performance.
AB  - In 2001, the Quality Initiative from the Department of Health and Human Services
      resulted in the development of a set of core measures focused on five patient
      populations. Although not part of the original list of providers able to document
      core measures involving medications, pharmacists were added to the list in
      November 2007. Within the set of core measures, there are 22 of 44 (50%) that are
      medication related. The authors' purpose is to describe the role of a pharmacist
      in meeting core measurements and provide an example of how a pharmacist is
      utilized at our institution.

PMID- 24032986
TI  - Puerperal sepsis: a traveller's tale.

PMID- 24032988
TI  - Decreased head circumference in shunt-treated compared with healthy children.
AB  - OBJECT: In this study, the authors' goal was to compare head circumference in
      hydrocephalic children during the first 4 years of ventriculoperitoneal (VP)
      shunt treatment with data on healthy children and to investigate predictors of
      skull growth in children with a VP shunt. METHODS: Children from western Sweden
      treated for hydrocephalus with an initial VP shunt insertion performed between
      2001 and 2006 who were younger than 12 months of age at the time of surgery were
      included. Children with major brain malformations, craniofacial syndromes, large
      cysts, and tumors were excluded. Head circumference, weight, and height at 9
      defined ages up to 4 years were obtained and compared with data from a reference
      population of 3650 healthy children using the standard deviation score (SDS).
      Predictors (length, weight, etiology of hydrocephalus, valve type, number of
      revisions, valve setting, number of adjustments, and time of first surgery) for
      head circumference SDS and changes in head circumference SDS from shunt insertion
      at 1 year to last measurement were analyzed using bivariate and multiple linear
      regression analysis. RESULTS: Fifty children were included. The mean SDSs for
      head circumference in shunt-treated compared with healthy children were 1.95 +/-
      2.50 at shunt insertion (p < 0.001, n = 44), 0.38 +/- 1.97 at 1 year (p = 0.27, n
      = 33), -0.96 +/- 2.05 at 2 years (p = 0.046, n = 21), -1.39 +/- 2.25 at 3 years
      (p = 0.026, n = 16), and 0.63 +/- 3.34 at 4 years (p = 0.73, n = 4). Significant
      predictors for low head circumference SDS at 1 year of age were low weight (p =
      0.002) and short height (p = 0.022) and at last measurement low weight (p <
      0.0001), short height (p = 0.002), and 1-4 shunt revisions (p = 0.034). A
      significant predictor for change in head circumference SDS from shunt insertion
      to 1 year of age was the number of shunt valve revisions (p = 0.04) and at last
      measurement an etiology of intraventricular hemorrhage (p = 0.0058). CONCLUSIONS:
      Shunt-treated children have smaller head circumferences at 2 and 3 years of age
      than healthy children. Low weight, short height, etiology of intraventricular
      hemorrhage, and frequent shunt valve revisions are predictors for decreased head
      circumference. Prospective, randomized studies comparing skull growth using fixed
      and adjustable pressure-regulated shunt valves and flow-regulated valves are
      needed.

PMID- 24032989
TI  - Safety of surgical treatment for patients with scoliosis and surgically corrected
      congenital cardiac malformations: a comparison with patients with scoliosis and
      normal hearts.
AB  - OBJECT: The safety of spinal fusion has been poorly studied in children with
      surgically corrected congenital cardiac malformations (CCMs). The objective of
      this study was to evaluate the safety of spinal fusion in patients with CCMs
      following cardiac surgery. METHODS: A retrospective study was conducted on 32
      patients with scoliosis who received surgical treatment for their CCMs (CCM
      group). Sixty-four age- and sex-matched patients with scoliosis and normal hearts
      who received spinal fusion served as the control group. These 2 groups were
      compared for demographic distribution, blood loss, transfusion requirements, and
      incidence of postoperative complications. RESULTS: The ages, curve pattern
      distributions, and number of levels fused were similar between the 2 groups
      before spinal fusion. Overall, a total of 7 patients in the CCM group (21.9%) and
      5 (7.8%) in the control group had documented postoperative complications. The
      perioperative allogenic blood transfusion rate and mean red blood cell
      transfusion requirement in the CCM group were significantly higher than those
      found in patients in the control group (68.7% vs 28.1%, respectively, p = 0.000;
      and 2.68 +/- 2.76 units/patient vs 0.76 +/- 1.07 units/patient, respectively, p =
      0.011). In the CCM group, a preoperative major curve magnitude >= 80 degrees  was
      the most accurate indicator of an increased risk for a major complication (p =
      0.019), whereas no statistically significant correlation was noted between
      postoperative complications and age, type of congenital heart disease, operative
      duration, and estimated blood loss during the operation and transfusion.
      CONCLUSIONS: Spinal fusion subsequent to prior cardiac surgery is relatively safe
      and effective in correcting the spinal deformity for patients with scoliosis and
      surgically corrected CCMs. A preoperative major curve magnitude >= 80 degrees 
      may be a risk factor in predicting postoperative complications in scoliotic
      patients with surgically corrected CCMs.

PMID- 24032987
TI  - Cholinergic interactions between donepezil and prucalopride in human colon:
      potential to treat severe intestinal dysmotility.
AB  - BACKGROUND AND PURPOSE: Cholinesterase inhibitors such as neostigmine are used
      for acute colonic pseudo-obstruction, but cardio-bronchial side-effects limit
      use. To minimize side-effects, lower doses could be combined with a 5-HT4
      receptor agonist, which also facilitates intestinal cholinergic activity.
      However, safety concerns, especially in the elderly, require drugs with good
      selectivity of action. These include the AChE inhibitor donepezil (used for
      Alzheimer's disease, with reduced cardio-bronchial liability) and prucalopride,
      the first selective, clinically available 5-HT4 receptor agonist. This study
      examined their individual and potential synergistic activities in human colon.
      EXPERIMENTAL APPROACH: Neuronally mediated muscle contractions and relaxations of
      human colon were evoked by electrical field stimulation (EFS) and defined
      phenotypically as cholinergic, nitrergic or tachykinergic using pharmacological
      tools; the effects of drugs were determined as changes in 'area under the curve'.
      KEY RESULTS: Prucalopride increased cholinergically mediated contractions (EC50
      855 nM; 33% maximum increase), consistent with its ability to stimulate
      intestinal motility; donepezil (477%) and neostigmine (2326%) had greater
      efficacy. Concentrations of donepezil (30-100 nM) found in venous plasma after
      therapeutic doses had minimal ability to enhance cholinergic activity. However,
      donepezil (30 nM) together with prucalopride (3, 10 MUM) markedly increased EFS
      evoked contractions compared with prucalopride alone (P = 0.04). For example, the
      increases observed with donepezil and prucalopride 10 MUM together or alone were,
      respectively, 105 +/- 35%, 4 +/- 6% and 35 +/- 21% (n = 3-7, each concentration).
      CONCLUSIONS AND IMPLICATIONS: Potential synergy between prucalopride and
      donepezil activity calls for exploration of this combination as a safer, more
      effective treatment of colonic pseudo-obstruction.

PMID- 24032990
TI  - Tolerance of early pallidal stimulation in pediatric generalized dystonia.
AB  - The authors report on 2 cases of pediatric generalized dystonia with a DYT1
      mutation; the patients, an 11-year-old girl and a 9-year-old boy, underwent
      chronic, pallidal deep brain stimulation (DBS) of the globus pallidus internus
      (GPi). The dystonic postures in both cases showed dramatic improvements with
      pallidal DBS, but each patient's symptoms gradually recurred within a year,
      irrespective of exhaustive readjustments of the stimulation settings. After the
      recurrence of the dystonic symptoms, the DBS leads were replaced within the GPi
      in one patient (Case 1) and additional DBS leads were implanted into the
      bilateral subthalamic nuclei in the other patient (Case 2). Neither measure
      produced any further clinical benefit, and the patient in Case 2 died of status
      dystonicus 2 days after reoperation. These findings suggest that early pallidal
      DBS for pediatric dystonia is indeed effective, although there are some cases in
      which its therapeutic effect is lost. One possible reason may be the ability of
      the preadolescent brain to tolerate chronic electrical stimuli during the active
      maturation process. 

PMID- 24032991
TI  - Congenital giant plexiform neurofibroma with occipital calvarial dysplasia in
      association with meningoencephalocele in neurofibromatosis Type 1 and segmental
      neurofibromatosis: report of 2 cases.
AB  - Giant plexiform neurofibroma (GPNF) of the scalp is an extremely rare lesion
      reported in association with neurofibromatosis. Occipital location of GPNF is
      even more infrequent, especially in association with occipital dysplasia (OD).
      The authors report 2 pediatric cases of GPNF associated with OD. The first case
      had an associated meningoencephalocele, and the second had large vascular
      channels within the lesion and the dominant ipsilateral transverse sinus lying in
      the center of the calvarial defect. The authors present these 2 unusual cases
      with a review of literature and discuss the radiological findings, theories of
      etiopathogenesis of the OD, and management dilemmas.

PMID- 24032992
TI  - Response to Bortolotti et al. 2012--a re-evaluation of our polymerase chain
      reaction-restriction fragment length polymorphism genotyping method.

PMID- 24032993
TI  - Spinal intramedullary ependymal cyst--current concepts for diagnosis and surgical
      management.
AB  - We describe a case of a 48-year-old woman who presented with neck pain and
      progressive left arm weakness. Magnetic Resonance Imaging showed a cervical
      intramedullary cystic lesion. The lesion was removed and neuropathological
      analysis revealed an ependymal cyst.

PMID- 24032994
TI  - Accelerating the controlled synthesis of metal-organic frameworks by a
      microfluidic approach: a nanoliter continuous reactor.
AB  - Segmented microfluidics was applied to the ultrafast crystallization of
      dicarboxylate based MIL-88B type metal-organic frameworks (MOFs; Fe-MIL-88B-NH2,
      Fe-MIL-88B, and Fe-MIL-88B-Br). Particular attention was paid to the influence of
      the temperature, residence time, and slug volume on the size and crystal size
      distribution of the MOFs. Average sizes in the 90-900 nm range with relatively
      narrow crystal size distributions were obtained with residence times as short as
      20 s depending on the MOF type and synthesis conditions. 

PMID- 24032996
TI  - Abstracts of the 101st FDI Annual World Dental Congress.

PMID- 24032995
TI  - Utility of cross-matched platelet transfusions in patients with hypoproliferative
      thrombocytopenia: a systematic review.
AB  - BACKGROUND: Multiply transfused hypoproliferative thrombocytopenic (HT) patients
      with alloimmune transfusion refractoriness require specially selected platelets
      (PLTs). Cross-matching apheresis PLTs is a popular support option, avoiding
      requirements for large panels of typed donors for HLA-based selection. We
      undertook a systematic review of the utility of various cross-matching techniques
      on mortality reduction, prevention of hemorrhage, alloimmunization and
      refractoriness, and improvement in PLT utilization or count increments. STUDY
      DESIGN AND METHODS: A systematic review to December 2012 was conducted of
      MEDLINE, EMBASE, and Cochrane databases along with a bibliographic search of
      pertinent references. RESULTS: Of 146 retrieved citations, 20 met inclusion
      criteria. Eleven more were chosen from bibliographies, describing 29 unique
      cohorts. All but five enrolled transfusion-refractory, predominantly
      alloimmunized patients. Cross-match impact on mortality and hemorrhage could not
      be assessed from these studies. Two studies demonstrated durable corrected count
      increments and/or breadth of alloimmunization throughout cross-match support;
      none addressed development or persistence of refractoriness. In alloimmunized
      refractory patients and nonrefractory cohorts with greater than 25%
      alloimmunization, higher increments were seen with cross-match-compatible PLTs
      than incompatible or un-cross-matched units. In two nonrefractory,
      nonalloimmunized cohorts, the lack of utility of cross-match was reflected by
      test sensitivity of less than 20%. Comparison of cross-matched PLT success with
      that of HLA-identical units revealed inferior success rates for the former in one
      study and equivalent rates in another. No trend was observed regarding relative
      utility of the various commonly employed techniques. CONCLUSION: Cross-matched
      PLTs are useful in increasing PLT counts in alloimmunized, transfusion-refractory
      HT patients, but data about their impact on hemorrhage and mortality are lacking.

PMID- 24032997
TI  - Lichen sclerosus associated with perineal urethrostomy.

PMID- 24032998
TI  - Interaction of azole compounds with DOPC and DOPC/ergosterol bilayers by spin
      probe EPR spectroscopy: implications for antifungal activity.
AB  - The influence of two antifungal azoles, the newly synthesized compound CPA18 and
      the commercial drug fluconazole (FLC), on the physical state of 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC) and DOPC/ergosterol bilayers was investigated by
      spin probe electron paramagnetic resonance (EPR) spectroscopy with the aim of
      ascertaining if direct interactions with the plasma membrane are implied in the
      mechanism of action against Candida albicans . 5- and 16-Doxyl-stearic acids (5
      DSA and 16-DSA, respectively) were employed to this purpose, and EPR spectra were
      acquired in the 0 to 40  degrees C temperature range. Spectral line shapes were
      analyzed within the theory for slow motion EPR using a microscopically ordered
      macroscopically disordered model to describe the DOPC multilamellar vesicles and
      an axially symmetric Brownian model for the spin probe motion. For CPA18
      remarkable changes in the molecular organization and dynamics of the phospholipid
      bilayers were found in the region immediately below the polar head groups, probed
      by 5-DSA, whereas the bilayer core, probed by 16-DSA, was only slightly affected.
      On the other hand, no effects of FLC on DOPC bilayers were revealed in the
      regions examined. Small differences were observed between DOPC and
      DOPC/ergosterol systems. The direct interactions of CPA18 with model membranes
      here highlighted may contribute to the observed fungicidal properties against
      both fluconazole-sensitive and -resistant C. albicans strains. 

PMID- 24032999
TI  - Glycemic control and urinary incontinence in women with diabetes mellitus.
AB  - BACKGROUND: Although many studies have shown that diabetes increases the risk for
      urinary incontinence, it is unclear whether poor glycemic control in women with
      diabetes is associated with incontinence. This study aims to determine the
      relationship between the hemoglobin A1c (HbA1c) level and urinary incontinence in
      a large, diverse cohort of older women. METHODS: We examined 6026 older women who
      responded to a survey (62% response rate) and were enrolled in the Diabetes and
      Aging Study, an ethnically stratified random sample of patients with diabetes
      enrolled in Kaiser Permanente Northern California. Our primary independent
      variable was the mean of all HbA1c measurements in the year preceding the survey.
      Outcomes included the presence/absence of incontinence and limitations in daily
      activities due to incontinence. We used modified Poisson regression and ordinal
      logistic regression models to account for age, race, body mass index, parity,
      diabetes treatment, duration of diabetes, and comorbidity. RESULTS: Sixty-five
      percent of women reported incontinence (mean age 59+/-10 years). After
      adjustment, HbA1c levels were not associated with the presence or absence of
      incontinence. However, among women reporting incontinence, HbA1c >=9% was
      associated with more limitations due to incontinence than HbA1c <6% (adjusted
      odds ratio 1.67, 95% confidence interval: 1.09-2.57). CONCLUSION: In this cross
      sectional analysis, HbA1c level is not associated with the presence or absence of
      incontinence. However, for women with incontinence, poor glycemic control (HbA1c
      >=9%) is associated with more limitations in daily activities due to
      incontinence. Longitudinal studies are needed to determine whether improving
      glycemic control to HbA1c <9% leads to fewer limitations in daily activities due
      to incontinence.

PMID- 24033000
TI  - Contraceptive history, unintended pregnancy, and contraceptive method choice
      among urban low-income women.
AB  - BACKGROUND: Nearly half of pregnancies in the United States are unintended, a
      proportion that has remained constant in the last decade. Half of unintended
      pregnancies occur among women not using any contraception, but little is known
      about how contraceptive history and contraceptive priorities predict
      contraceptive method choice. METHODS: Among 1454 women not currently seeking
      pregnancy who completed a computer-based contraceptive assessment module at an
      urban reproductive health center, factors associated with not obtaining a
      contraceptive method were assessed. RESULTS: The 1454 participants were low
      income (98% had incomes <200% federal poverty level), predominantly Hispanic
      (71%), and foreign-born (76%). None were seeking to become pregnant, but 15% did
      not obtain a method of contraception. In adjusted analyses, women who had ever
      had an unintended pregnancy-41% of the sample-were significantly more likely to
      leave their visit without receiving a method (adjusted odds ratio [AOR]=1.67, 95%
      confidence interval [CI]: 1.21-2.30), as were women who were not using
      contraception at the start of their visit (AOR=3.82, 95% CI: 2.73-5.35). In an
      adjusted model, prioritizing no hormones or the preference of not wanting to
      interrupt sex to use a method was not a significant predictor of obtaining a
      method. CONCLUSIONS: Analyses revealed that women at higher risk of unintended
      pregnancy identified by their contraceptive histories were significantly more
      likely to leave their healthcare visit without a method of contraception.
      Additional research is needed on ways to help women obtain effective, medically
      indicated contraceptive methods that fit their reproductive life goals,
      priorities, and preferences.

PMID- 24033001
TI  - In honour of Professor Vladimir Torchilin, Recipient of the Journal of Drug
      Targeting's Life-Time Achievement Award for 2013.

PMID- 24033002
TI  - Emergency obstetric simulation training: how do we know where we are going, if we
      don't know where we have been?
AB  - BACKGROUND: Obstetric emergencies contribute significantly to maternal morbidity
      and mortality. Current training in the management of obstetric emergencies in
      Australia and internationally focusses on utilising a multidisciplinary
      simulation-based model. Arguments for and against this type of training exist,
      using both economic and clinical reasoning. AIMS: To identify the evidence base
      for the clinical impact of simulation training in obstetric emergencies and to
      address some of the concerns regarding appropriate delivery of obstetric
      emergency training in the Australian setting. METHODS: A literature search was
      performed to identify research undertaken in the area of obstetric emergency
      training. The initial literature search using broad search terms identified 887
      articles which were then reviewed and considered for inclusion if they provided
      original research with a specific emphasis on the impact of training on clinical
      outcomes. RESULTS: Ninety-two articles were identified, comprising evidence in
      the following clinical situations: eclampsia, shoulder dystocia, postpartum
      haemorrhage, maternal collapse, cord prolapse and teamwork training. Evidence
      exists for a benefit in knowledge or skills gained from simulation training and
      for the benefit of training in small units without access to high-fidelity
      equipment or facilities. CONCLUSIONS: Evidence exists for a positive impact of
      training in obstetric emergencies, although the majority of the available
      evidence applies to evaluation at the level of participants' confidence,
      knowledge or skills rather than at the level of impact on clinical outcomes. The
      model of simulation-based training is an appropriate one for the Australian
      setting and should be further utilised in rural and remote settings.

PMID- 24033003
TI  - SPG4-related hereditary spastic paraplegia: frequency and mutation spectrum in
      Brazil.

PMID- 24033004
TI  - Integer quantum Hall state in two-component Bose gases in a synthetic magnetic
      field.
AB  - We study two-component (or pseudospin-1/2) Bose gases in a strong synthetic
      magnetic field. Using exact diagonalization, we show that a bosonic analog of an
      integer quantum Hall state with no intrinsic topological order appears at the
      total filling factor nu=1+1 when the strengths of intracomponent and
      intercomponent interactions are comparable with each other. This provides a prime
      example of a symmetry-protected topological phase in a controlled setting of
      quantum gases. The real-space entanglement spectrum of this state is found to be
      comprised of counterpropagating chiral modes consistent with the edge theory
      derived from an effective Chern-Simons theory. 

PMID- 24033005
TI  - No-go theorems for psi-epistemic models based on a continuity assumption.
AB  - The quantum state psi is a mathematical object used to determine the
      probabilities of different outcomes when measuring a physical system. Its
      fundamental nature has been the subject of discussions since the inception of
      quantum theory. Is it ontic, that is, does it correspond to a real property of
      the physical system? Or is it epistemic, that is, does it merely represent our
      knowledge about the system? Assuming a natural continuity assumption and a weak
      separability assumption, we show here that epistemic interpretations of the
      quantum state are in contradiction with quantum theory. Our argument is different
      from the recent proof of Pusey, Barrett, and Rudolph and it already yields a
      nontrivial constraint on psi-epistemic models using a single copy of the system
      in question. 

PMID- 24033006
TI  - Dynamic stabilization of a quantum many-body spin system.
AB  - We demonstrate dynamic stabilization of a strongly interacting quantum spin
      system realized in a spin-1 atomic Bose-Einstein condensate. The spinor Bose
      Einstein condensate is initialized to an unstable fixed point of the spin-nematic
      phase space, where subsequent free evolution gives rise to squeezing and quantum
      spin mixing. To stabilize the system, periodic microwave pulses are applied that
      rotate the spin-nematic many-body fluctuations and limit their growth. The
      stability diagram for the range of pulse periods and phase shifts that stabilize
      the dynamics is measured and compares well with a stability analysis. 

PMID- 24033007
TI  - Quantum chaos in SU(3) models with trapped ions.
AB  - A scheme to generate long-range spin-spin interactions between three-level ions
      in a chain is presented, providing a feasible experimental route to the rich
      physics of well-known SU(3) models. In particular, we demonstrate different
      signatures of quantum chaos which can be controlled and observed in experiments
      with trapped ions. 

PMID- 24033008
TI  - Tunnel ionization dynamics of bound systems in laser fields: how long does it
      take for a bound electron to tunnel?
AB  - A numerical method is developed by which the tunnel ionization dynamics of bound
      systems in laser fields can be isolated from the total wave function, as given by
      the time-dependent Schrodinger equation. The analysis of the numerical data for a
      step function field reveals the following definition for the tunnel time. It is
      the time it takes the ground state to develop the underbarrier wave function
      components necessary for reaching the static field ionization rate. This
      definition is generalized to time varying laser fields. The tunnel time is found
      to scale with the Keldysh tunnel time. Our Letter establishes the physical
      meaning of the tunnel time, its relation to the Keldysh tunnel time, and suggests
      how it can be measured. 

PMID- 24033009
TI  - Topological order in the projected entangled-pair states formalism: transfer
      operator and boundary Hamiltonians.
AB  - We study the structure of topological phases and their boundaries in the
      projected entangled-pair states (PEPS) formalism. We show how topological order
      in a system can be identified from the structure of the PEPS transfer operator
      and subsequently use these findings to analyze the structure of the boundary
      Hamiltonian, acting on the bond variables, which reflects the entanglement
      properties of the system. We find that in a topological phase, the boundary
      Hamiltonian consists of two parts: A universal nonlocal part which encodes the
      nature of the topological phase and a nonuniversal part which is local and
      inherits the symmetries of the topological model, which helps to infer the
      structure of the boundary Hamiltonian and thus possibly of the physical edge
      modes. 

PMID- 24033010
TI  - Waveguide-QED-based photonic quantum computation.
AB  - We propose a new scheme for quantum computation using flying qubits--propagating
      photons in a one-dimensional waveguide interacting with matter qubits. Photon
      photon interactions are mediated by the coupling to a four-level system, based on
      which photon-photon pi-phase gates (CONTROLLED-NOT) can be implemented for
      universal quantum computation. We show that high gate fidelity is possible, given
      recent dramatic experimental progress in superconducting circuits and photonic
      crystal waveguides. The proposed system can be an important building block for
      future on-chip quantum networks.

PMID- 24033011
TI  - Quantum simulation of noncausal kinematic transformations.
AB  - We propose the implementation of Galileo group symmetry operations or, in
      general, linear coordinate transformations in a quantum simulator. With an
      appropriate encoding, unitary gates applied to our quantum system give rise to
      Galilean boosts or spatial and time parity operations in the simulated dynamics.
      This framework provides us with a flexible toolbox that enhances the versatility
      of quantum simulation theory, allowing the direct access to dynamical quantities
      that would otherwise require full tomography. Furthermore, this method enables
      the study of noncausal kinematics and phenomena beyond special relativity in a
      quantum controllable system. 

PMID- 24033012
TI  - Relativistic motion generates quantum gates and entanglement resonances.
AB  - We show that the relativistic motion of a quantum system can be used to generate
      quantum gates. The nonuniform acceleration of a cavity is used to generate well
      known two-mode quantum gates in continuous variables. Observable amounts of
      entanglement between the cavity modes are produced through resonances that appear
      by repeating periodically any trajectory. 

PMID- 24033013
TI  - Universal fault-tolerant quantum computation with only transversal gates and
      error correction.
AB  - Transversal implementations of encoded unitary gates are highly desirable for
      fault-tolerant quantum computation. Though transversal gates alone cannot be
      computationally universal, they can be combined with specially distilled resource
      states in order to achieve universality. We show that "triorthogonal" stabilizer
      codes, introduced for state distillation by Bravyi and Haah [Phys. Rev. A 86,
      052329 (2012)], admit transversal implementation of the controlled-controlled-Z
      gate. We then construct a universal set of fault-tolerant gates without state
      distillation by using only transversal controlled-controlled-Z, transversal
      Hadamard, and fault-tolerant error correction. We also adapt the distillation
      procedure of Bravyi and Haah to Toffoli gates, improving on existing Toffoli
      distillation schemes. 

PMID- 24033014
TI  - Partial-measurement backaction and nonclassical weak values in a superconducting
      circuit.
AB  - We realize indirect partial measurement of a transmon qubit in circuit quantum
      electrodynamics by interaction with an ancilla qubit and projective ancilla
      measurement with a dedicated readout resonator. Accurate control of the
      interaction and ancilla measurement basis allows tailoring the measurement
      strength and operator. The tradeoff between measurement strength and qubit
      backaction is characterized through the distortion of a qubit Rabi oscillation
      imposed by ancilla measurement in different bases. Combining partial and
      projective qubit measurements, we provide the solid-state demonstration of the
      correspondence between a nonclassical weak value and the violation of a Leggett
      Garg inequality. 

PMID- 24033015
TI  - Exact lattice Boltzmann equation.
AB  - The lattice Boltzmann equation is derived from the Bhatnagar-Gross-Krook kinetic
      equation using the Euler-Maclaurin integration formula. Unlike previous attempts
      to connect the lattice Boltzmann method with the kinetic theory, the result is
      free of any relaxation-type approximation. It shows that the conventional lattice
      Bhatnagar-Gross-Krook simulations of hydrodynamics belong to a parameter domain
      which is disconnected from the kinetic theory domain. 

PMID- 24033016
TI  - Near-Heisenberg-limited atomic clocks in the presence of decoherence.
AB  - The ultimate stability of atomic clocks is limited by the quantum noise of the
      atoms. To reduce this noise it has been suggested to use entangled atomic
      ensembles with reduced atomic noise. Potentially this can push the stability all
      the way to the limit allowed by the Heisenberg uncertainty relation, which is
      denoted the Heisenberg limit. In practice, however, entangled states are often
      more prone to decoherence, which may prevent reaching this performance. Here we
      present an adaptive measurement protocol that in the presence of a realistic
      source of decoherence enables us to get near-Heisenberg-limited stability of
      atomic clocks using entangled atoms. The protocol may thus realize the full
      potential of entanglement for quantum metrology despite the detrimental influence
      of decoherence. 

PMID- 24033017
TI  - Efficient atomic clocks operated with several atomic ensembles.
AB  - Atomic clocks are typically operated by locking a local oscillator (LO) to a
      single atomic ensemble. In this Letter, we propose a scheme where the LO is
      locked to several atomic ensembles instead of one. This results in an exponential
      improvement compared to the conventional method and provides a stability of the
      clock scaling as (alphaN)(-m/2) with N being the number of atoms in each of the m
      ensembles and alpha a constant depending on the protocol being used to lock the
      LO.

PMID- 24033018
TI  - Axial symmetry breaking in self-induced flavor conversionof supernova neutrino
      fluxes.
AB  - Neutrino-neutrino refraction causes self-induced flavor conversion in dense
      neutrino fluxes. For the first time, we include the azimuth angle of neutrino
      propagation as an explicit variable and find a new generic multi-azimuth-angle
      instability which, for simple spectra, occurs in the normal neutrino mass
      hierarchy. Matter suppression of this instability in supernovae requires larger
      densities than the traditional bimodal case. The new instability shows explicitly
      that solutions of the equations for collective flavor oscillations need not
      inherit the symmetries of initial or boundary conditions. This change of paradigm
      requires reconsideration of numerous results in this field. 

PMID- 24033019
TI  - Internal bremsstrahlung signature of real scalar dark matter and consistency with
      thermal relic density.
AB  - A gamma-ray excess from the Galactic center consistent with line emission around
      130 GeV was recently found in the Fermi-LAT data. Although the Fermi-LAT
      Collaboration has not confirmed its significance, such a signal would be a clear
      signature of dark matter annihilation. Until now, there have been many attempts
      to explain the excess by dark matter. However, these efforts tend to give too
      small cross sections into photons if consistency with the correct thermal relic
      density of dark matter is required. In this Letter, we consider a simple Yukawa
      interaction that can be compatible with both aspects and show which parameters
      are favored. 

PMID- 24033020
TI  - Can all cosmological observations be accurately interpreted with a unique
      geometry?
AB  - The recent analysis of the Planck results reveals a tension between the best fits
      for (Omega(m0), H(0)) derived from the cosmic microwave background or baryonic
      acoustic oscillations on the one hand, and the Hubble diagram on the other hand.
      These observations probe the Universe on very different scales since they involve
      light beams of very different angular sizes; hence, the tension between them may
      indicate that they should not be interpreted the same way. More precisely, this
      Letter questions the accuracy of using only the (perturbed) Friedmann-Lemaitre
      geometry to interpret all the cosmological observations, regardless of their
      angular or spatial resolution. We show that using an inhomogeneous "Swiss-cheese"
      model to interpret the Hubble diagram allows us to reconcile the inferred value
      of Omega(m0) with the Planck results. Such an approach does not require us to
      invoke new physics nor to violate the Copernican principle.

PMID- 24033021
TI  - Evidence for maximal acceleration and singularity resolution in covariant loop
      quantum gravity.
AB  - A simple argument indicates that covariant loop gravity (spin foam theory)
      predicts a maximal acceleration and hence forbids the development of curvature
      singularities. This supports the results obtained for cosmology and black holes
      using canonical methods. 

PMID- 24033022
TI  - Lattice study of radiative J/psi decay to a tensor glueball.
AB  - The radiative decay of J/psi into a pure gauge tensor glueball is studied in the
      quenched lattice QCD formalism. With two anisotropic lattices, the multipole
      amplitudes E1(0), M2(0), and E3(0) are obtained to be 0.114(12)(6) GeV, 
      0.011(5)(1)  GeV, and 0.023(8)(1) GeV, respectively. The first error comes from
      the statistics, the Q2 interpolation, and the continuum extrapolation, while the
      second is due to the uncertainty of the scale parameter r0(-1)=410(20)  MeV.
      Thus, the partial decay width Gamma(J/psi->gammaG(2++)) is estimated to be
      1.01(22)(10) keV, which corresponds to a large branch ratio 1.1(2)(1)*10(-2). The
      phenomenological implication of this result is also discussed.

PMID- 24033023
TI  - Spacetime and flux tube S-matrices at finite coupling for N=4 supersymmetric Yang
      Mills theory.
AB  - We propose a nonperturbative formulation of planar scattering amplitudes in N=4
      supersymmetric Yang-Mills theory, or, equivalently, polygonal Wilson loops. The
      construction is based on the operator product expansion approach and introduces a
      new decomposition of the Wilson loop in terms of fundamental building blocks
      named pentagon transitions. These transitions satisfy a simple relation to the
      worldsheet S matrix on top of the so-called Gubser-Klebanov-Polyakov vacuum which
      allows us to bootstrap them at any value of the coupling. In this Letter we
      present a subsector of the full solution which we call the gluonic part. We match
      our results with both weak and strong coupling data available in the literature. 

PMID- 24033024
TI  - Impact of a CP-violating Higgs sector: from LHC to baryogenesis.
AB  - We observe a generic connection between LHC Higgs data and electroweak
      baryogenesis: the particle that contributes to the CP-odd hgg or hgammagamma
      vertex would provide the CP-violating source during a first-order phase
      transition. It is illustrated in the two Higgs doublet model that a common
      complex phase controls the lightest Higgs properties at the LHC, electric dipole
      moments, and the CP-violating source for electroweak baryogenesis. We perform a
      general parametrization of Higgs effective couplings and a global fit to the LHC
      Higgs data. Current LHC measurements prefer a nonzero phase for tanbeta?1 and
      electric dipole moment constraints still allow an order-one phase for tanbeta~1,
      which gives sufficient room to generate the correct cosmic baryon asymmetry. We
      also give some prospects in the direct measurements of CP violation in the Higgs
      sector at the LHC.

PMID- 24033025
TI  - Unravelling tth via the matrix element method.
AB  - Associated production of the Higgs boson with a top-antitop pair is a key channel
      to gather further information on the nature of the newly discovered boson at the
      LHC. Experimentally, however, its observation is very challenging due to the
      combination of small rates, difficult multijet final states, and overwhelming
      backgrounds. In the standard model, the largest number of events is expected when
      h->bb, giving rise to a W+ W- bbbb signature, deluged in tt + jets. A promising
      strategy to improve the sensitivity is to maximally exploit the theoretical
      information on the signal and background processes by means of the matrix element
      method. We show how, despite the complexity of the final state, the method can be
      efficiently applied to discriminate the signal against combinatorial and tt +
      jets backgrounds. Remarkably, we find that a moderate integrated luminosity in
      the next LHC run will be enough to make the signature involving both W's decaying
      leptonically as sensitive as the single-lepton one.

PMID- 24033026
TI  - Pion distribution amplitude from lattice QCD.
AB  - A method is explained through which a pointwise accurate approximation to the
      pion's valence-quark distribution amplitude (PDA) may be obtained from a limited
      number of moments. In connection with the single nontrivial moment accessible in
      contemporary simulations of lattice-regularized QCD, the method yields a PDA that
      is a broad concave function whose pointwise form agrees with that predicted by
      Dyson-Schwinger equation analyses of the pion. Under leading-order evolution, the
      PDA remains broad to energy scales in excess of 100 GeV, a feature which signals
      persistence of the influence of dynamical chiral symmetry breaking. Consequently,
      the asymptotic distribution phipi(asy)(x) is a poor approximation to the pion's
      PDA at all such scales that are either currently accessible or foreseeable in
      experiments on pion elastic and transition form factors. Thus, related
      expectations based on phi phipi(asy)(x) should be revised.

PMID- 24033028
TI  - Time-dependent theory of angular correlations in sequential double ionization.
AB  - In this work, we emphasize the importance of the bound-state dynamics to the two
      electron ejection in double ionization processes. The conclusions of the present
      study are pertinent to all excitation or decay processes that proceed via well
      defined intermediate states. A general strong-field time-dependent density matrix
      theory is established and applied to the case of neon, allowing us to analyze the
      role of the ionizing field in the interpretation of reported angular patterns [M.
      Kurka et al., J. Phys. B 42, 141002 (2009); A. S. Kheifets, J. Phys. B 42, 134016
      (2009)] and in the dynamic ionic alignment. The present analysis reveals that
      short-pulse coherent excitation of the neon ionic doublet 2P(1/2,3/2) leads to
      quantum beats in the two-electron angular correlation patterns.

PMID- 24033027
TI  - Charge form factor and sum rules of electromagnetic response functions in 12C.
AB  - An ab initio calculation of the 12C elastic form factor and sum rules of
      longitudinal and transverse response functions measured in inclusive (e, e')
      scattering are reported, based on realistic nuclear potentials and
      electromagnetic currents. The longitudinal elastic form factor and sum rule are
      found to be in satisfactory agreement with available experimental data. A direct
      comparison between theory and experiment is difficult for the transverse sum
      rule. However, it is shown that the calculated transverse sum rule has large
      contributions from two-body currents, indicating that these mechanisms lead to a
      significant enhancement of the quasielastic transverse response. This fact may
      have implications for the anomaly observed in recent neutrino quasielastic charge
      changing scattering experiments on 12C.

PMID- 24033029
TI  - Coherent control at its most fundamental: carrier-envelope-phase-dependent
      electron localization in photodissociation of a H2(+) molecular ion beam target.
AB  - Measurements and calculations of the absolute carrier-envelope-phase (CEP)
      effects in the photodissociation of the simplest molecule, H2(+), with a 4.5-fs
      Ti:sapphire laser pulse at intensities up to (4+/-2)*10(14)  W/cm2 are presented.
      Localization of the electron with respect to the two nuclei (during the
      dissociation process) is controlled via the CEP of the ultrashort laser pulses.
      In contrast to previous CEP-dependent experiments with neutral molecules, the
      dissociation of the molecular ions is not preceded by a photoionization process,
      which strongly influences the CEP dependence. Kinematically complete data are
      obtained by time- and position-resolved coincidence detection. The phase
      dependence is determined by a single-shot phase measurement correlated to the
      detection of the dissociation fragments. The experimental results show
      quantitative agreement with ab initio 3D time-dependent Schrodinger equation
      calculations that include nuclear vibration and rotation.

PMID- 24033030
TI  - Guaranteed convergence of the Kohn-Sham equations.
AB  - A sufficiently damped iteration of the Kohn-Sham (KS) equations with the exact
      functional is proven to always converge to the true ground-state density,
      regardless of the initial density or the strength of electron correlation, for
      finite Coulomb systems. We numerically implement the exact functional for one
      dimensional continuum systems and demonstrate convergence of the damped KS
      algorithm. More strongly correlated systems converge more slowly. 

PMID- 24033031
TI  - Evolution of interatomic Coulombic decay in the time domain.
AB  - During the past 15 years a novel decay mechanism of excited atoms has been
      discovered and investigated. This so-called interatomic Coulombic decay (ICD)
      involves the chemical environment of the electronically excited atom: the
      excitation energy is transferred (in many cases over long distances) to a
      neighbor of the initially excited particle usually ionizing that neighbor. It
      turned out that ICD is a very common decay route in nature as it occurs across
      van der Waals and hydrogen bonds. The time evolution of ICD is predicted to be
      highly complex, as its efficiency strongly depends on the distance of the atoms
      involved and this distance typically changes during the decay. Here we present
      the first direct measurement of the temporal evolution of ICD using a novel
      experimental approach. 

PMID- 24033032
TI  - Time-resolved measurement of interatomic coulombic decay in Ne2.
AB  - The lifetime of interatomic Coulombic decay (ICD) [L. S. Cederbaum et al., Phys.
      Rev. Lett. 79, 4778 (1997)] in Ne2 is determined via an extreme ultraviolet pump
      probe experiment at the Free-Electron Laser in Hamburg. The pump pulse creates a
      2s inner-shell vacancy in one of the two Ne atoms, whereupon the ionized dimer
      undergoes ICD resulting in a repulsive Ne+(2p(-1))-Ne+(2p(-1)) state, which is
      probed with a second pulse, removing a further electron. The yield of coincident
      Ne+-Ne2+ pairs is recorded as a function of the pump-probe delay, allowing us to
      deduce the ICD lifetime of the Ne2(+)(2s(-1)) state to be (150+/-50)  fs, in
      agreement with quantum calculations.

PMID- 24033033
TI  - Observation of transverse Bose-Einstein condensation via Hanbury Brown-Twiss
      correlations.
AB  - A fundamental property of a three-dimensional Bose-Einstein condensate is long
      range coherence; however, in systems of lower dimensionality, not only is the
      long-range coherence destroyed but additional states of matter are predicted to
      exist. One such state is a "transverse condensate," first predicted by van Druten
      and Ketterle [Phys. Rev. Lett. 79, 549 (1997)], in which the gas condenses in the
      transverse dimensions of a highly anisotropic trap while remaining thermal in the
      longitudinal dimension. Here, we detect the transition from a three-dimensional
      thermal gas to a gas undergoing transverse condensation by probing Hanbury Brown
      Twiss correlations. 

PMID- 24033034
TI  - Quantum jump approach for work and dissipation in a two-level system.
AB  - We apply the quantum jump approach to address the statistics of work in a driven
      two-level system coupled to a heat bath. We demonstrate how this question can be
      analyzed by counting photons absorbed and emitted by the environment in repeated
      experiments. We find that the common nonequilibrium fluctuation relations are
      satisfied identically. The usual fluctuation-dissipation theorem for linear
      response applies for weak dissipation and/or weak drive. We point out qualitative
      differences between the classical and quantum regimes. 

PMID- 24033035
TI  - Multicolor quantum metrology with entangled photons.
AB  - Entangled photons can be used to make measurements with an accuracy beyond that
      possible with classical light. While most implementations of quantum metrology
      have used states made up of a single color of photons, we show that entangled
      states of two colors can show supersensitivity to optical phase and path length
      by using a photonic crystal fiber source of photon pairs inside an
      interferometer. This setup is relatively simple and robust to experimental
      imperfections. We demonstrate sensitivity beyond the standard quantum limit and
      show superresolved interference fringes using entangled states of two, four, and
      six photons. 

PMID- 24033036
TI  - Optical spectrum analyzer with quantum-limited noise floor.
AB  - Interactions between atoms and lasers provide the potential for unprecedented
      control of quantum states. Fulfilling this potential requires detailed knowledge
      of frequency noise in optical oscillators with state-of-the-art stability. We
      demonstrate a technique that precisely measures the noise spectrum of an
      ultrastable laser using optical lattice-trapped 87Sr atoms as a quantum
      projection noise-limited reference. We determine the laser noise spectrum from
      near dc to 100 Hz via the measured fluctuations in atomic excitation, guided by a
      simple and robust theory model. The noise spectrum yields a 26(4) mHz linewidth
      at a central frequency of 429 THz, corresponding to an optical quality factor of
      1.6*10(16). This approach improves upon optical heterodyne beats between two
      similar laser systems by providing information unique to a single laser and
      complements the traditionally used Allan deviation which evaluates laser
      performance at relatively long time scales. We use this technique to verify the
      reduction of resonant noise in our ultrastable laser via feedback from an optical
      heterodyne beat. Finally, we show that knowledge of our laser's spectrum allows
      us to accurately predict the laser-limited stability for optical atomic clocks.

PMID- 24033037
TI  - Surface plasmons and nonlocality: a simple model.
AB  - Surface plasmons on metals can concentrate light into subnanometric volumes and
      on these near atomic length scales the electronic response at the metal interface
      is smeared out over a Thomas-Fermi screening length. This nonlocality is a
      barrier to a good understanding of atomic scale response to light and complicates
      the practical matter of computing the fields. In this Letter, we present a local
      analogue model and show that spatial nonlocality can be represented by replacing
      the nonlocal metal with a composite material, comprising a thin dielectric layer
      on top of a local metal. This method not only makes possible the quantitative
      analysis of nonlocal effects in complex plasmonic phenomena with unprecedented
      simplicity and physical insight, but also offers great practical advantages in
      their numerical treatment. 

PMID- 24033038
TI  - Harnessing optical vortex lattices in nematic liquid crystals.
AB  - By creating self-induced vortexlike defects in the nematic liquid crystal layer
      of a light valve, we demonstrate the realization of programable lattices of
      optical vortices with arbitrary distribution in space. On each lattice site,
      every matter vortex acts as a photonic spin-to-orbital momentum coupler and an
      array of circularly polarized input beams is converted into an output array of
      vortex beams with topological charges consistent with the matter lattice. The
      vortex arrangements are explained on the basis of light-induced matter defects of
      both signs and consistent topological rules. 

PMID- 24033039
TI  - Distribution of the smallest eigenvalue in the correlated Wishart model.
AB  - Wishart random matrix theory is of major importance for the analysis of
      correlated time series. The distribution of the smallest eigenvalue for Wishart
      correlation matrices is particularly interesting in many applications. In the
      complex and in the real case, we calculate it exactly for arbitrary empirical
      eigenvalues, i.e., for fully correlated Gaussian Wishart ensembles. To this end,
      we derive certain dualities of matrix models in ordinary space. We thereby
      completely avoid the otherwise unsurmountable problem of computing a highly
      nontrivial group integral. Our results are compact and much easier to handle than
      previous ones. Furthermore, we obtain a new universality for the distribution of
      the smallest eigenvalue on the proper local scale. 

PMID- 24033040
TI  - Extension of a suspended soap film: a homogeneous dilatation followed by new film
      extraction.
AB  - Liquid foams are widely used in industry for their high effective viscosity,
      whose local origin is still unclear. This Letter presents new results on the
      extension of a suspended soap film, in a configuration mimicking the elementary
      deformation occurring during foam shearing. We evidence a surprising two-step
      evolution: the film first extends homogeneously, then its extension stops, and a
      new thicker film is extracted from the meniscus. The second step is independent
      of the nature of the surfactant solution, whereas the initial extension is only
      observed for surfactant solutions with negligible dilatational moduli. We predict
      this complex behavior using a model based on Frankel's theory and on interface
      rigidification induced by confinement. 

PMID- 24033041
TI  - Annular fast electron transport in silicon arising from low-temperature
      resistivity.
AB  - Fast electron transport in Si, driven by ultraintense laser pulses, is
      investigated experimentally and via 3D hybrid particle-in-cell simulations. A
      transition from a Gaussian-like to an annular fast electron beam profile is
      demonstrated and explained by resistively generated magnetic fields. The results
      highlight the potential to completely transform the beam transport pattern by
      tailoring the resistivity-temperature profile at temperatures as low as a few eV.

PMID- 24033042
TI  - Rotational resonance of nonaxisymmetric magnetic braking in the KSTAR tokamak.
AB  - One of the important rotational resonances in nonaxisymmetric neoclassical
      transport has been experimentally validated in the KSTAR tokamak by applying
      highly nonresonant n=1 magnetic perturbations to rapidly rotating plasmas. These
      so-called bounce-harmonic resonances are expected to occur in the presence of
      magnetic braking perturbations when the toroidal rotation is fast enough to
      resonate with periodic parallel motions of trapped particles. The predicted and
      observed resonant peak along with the toroidal rotation implies that the toroidal
      rotation in tokamaks can be controlled naturally in favorable conditions to
      stability, using nonaxisymmetric magnetic perturbations. 

PMID- 24033043
TI  - Raman-induced interactions in a single-component Fermi gas near an s-wave
      Feshbach resonance.
AB  - Ultracold gases of interacting spin-orbit-coupled fermions are predicted to
      display exotic phenomena such as topological superfluidity and its associated
      Majorana fermions. Here, we experimentally demonstrate a route to strongly
      interacting single-component atomic Fermi gases by combining an s-wave Feshbach
      resonance (giving strong interactions) and spin-orbit coupling (creating an
      effective p-wave channel). We identify the Feshbach resonance by its associated
      atomic loss feature and show that, in agreement with our single-channel
      scattering model, this feature is preserved and shifted as a function of the spin
      orbit-coupling parameters. 

PMID- 24033044
TI  - Extended interplanar linking in graphite formed from vacancy aggregates.
AB  - The mechanical and electrical properties of graphite and related materials such
      as multilayer graphene depend strongly on the presence of defects in the lattice
      structure, particularly those which create links between adjacent planes. We
      present findings which suggest the existence of a new type of defect in the
      graphite or graphene structure which connects adjacent planes through continuous
      hexagonal sp2 bonding alone and can form through the aggregation of individual
      vacancy defects. The energetics and kinetics of the formation of this type of
      defect are investigated with atomistic density functional theory calculations.
      The resultant structures are then employed to simulate high resolution
      transmission electron microscopy images, which are compared to recent
      experimental images of electron irradiation damaged graphite.

PMID- 24033045
TI  - Free energy generalization of the Peierls potential in iron.
AB  - In body-centered-cubic (bcc) crystals, 1/2<111> screw dislocations exhibit high
      intrinsic lattice friction as a consequence of their nonplanar core structure,
      which results in a periodic energy landscape known as the Peierls potential U(P).
      The main features determining plastic flow, including its stress and temperature
      dependences, can be derived directly from this potential, hence its importance.
      In this Letter, we use thermodynamic integration to provide a full thermodynamic
      extension of U(P) for bcc Fe. We compute the Peierls free energy path as a
      function of stress and temperature and show that the critical stress vanishes at
      700 K, supplying the qualitative elements that explain plastic behavior in the
      athermal limit.

PMID- 24033046
TI  - Fluctuation-stabilized marginal networks and anomalous entropic elasticity.
AB  - We study the elastic properties of thermal networks of Hookean springs. In the
      purely mechanical limit, such systems are known to have a vanishing rigidity when
      their connectivity falls below a critical, isostatic value. In this work, we show
      that thermal networks exhibit a nonzero shear modulus G well below the isostatic
      point and that this modulus exhibits an anomalous, sublinear dependence on
      temperature T. At the isostatic point, G increases as the square root of T, while
      we find G?Talpha below the isostatic point, where alpha?0.8. We show that this
      anomalous T dependence is entropic in origin.

PMID- 24033047
TI  - Lead is not off center in PbTe: the importance of r-space phase information in
      extended x-ray absorption fine structure spectroscopy.
AB  - PbTe is a well-known thermoelectric material. Recent x-ray total scattering
      studies suggest that Pb moves off center along 100 in PbTe, by ~0.2  A at 300 K,
      producing a split Pb-Te pair distribution. We present an extended x-ray
      absorption fine structure spectroscopy (EXAFS) study of PbTe (and Tl doped PbTe)
      to determine if Pb or Te is off center. EXAFS provides sensitive r- or k-space
      phase information which can differentiate between a split peak for the Pb-Te
      distribution (indicative of off-center Pb) and a thermally broadened peak. We
      find no evidence for a split peak for Pb-Te or Te-Pb. At 300 K, the vibration
      amplitude for Pb-Te (or Te-Pb) is large; this thermally induced disorder is
      indicative of weak bonds, and the large disorder is consistent with the low
      thermal conductivity at 300 K. We also find evidence of an anharmonic potential
      for the nearest Pb-Te bonds, consistent with the overall anharmonicity found for
      the phonon modes. This effect is modeled by a "skew" factor (C3) which
      significantly improves the fit of the Pb-Te and Te-Pb peaks for the high
      temperature EXAFS data; C3 becomes significant above approximately 150-200 K. The
      consequences of these results will be discussed. 

PMID- 24033048
TI  - Direct evidence of two equilibration mechanisms in glassy polymers.
AB  - We investigated the kinetics of enthalpy recovery of several glass-forming
      polymers at temperatures significantly below the glass transition temperature
      (Tg) and for aging times up to one year. We find a double-step recovery at
      relatively low aging temperatures for the longest investigated aging times. The
      enthalpy recovered after the two-step decay approximately equals that expected by
      extrapolation from the melt. The two-step enthalpy recovery indicates the
      presence of two time scales for glass equilibration. The equilibration time of
      the first recovery step exhibits relatively weak temperature dependence, whereas
      that of the second step possesses pronounced temperature dependence, compatible
      with the Vogel-Fulcher-Tammann behavior. These results, while leaving open the
      question of the divergence of the relaxation time and that of a thermodynamic
      singularity at a finite temperature, reveal a complex scenario of glassy
      dynamics.

PMID- 24033049
TI  - Young's equation at the nanoscale.
AB  - In 1805, Thomas Young was the first to propose an equation to predict the value
      of the equilibrium contact angle of a liquid on a solid. Today, the force exerted
      by a liquid on a solid, such as a flat plate or fiber, is routinely used to
      assess this angle. Moreover, it has recently become possible to study wetting at
      the nanoscale using an atomic force microscope. Here, we report the use of
      molecular-dynamics simulations to investigate the force distribution along a 15
      nm fiber dipped into a liquid meniscus. We find very good agreement between the
      measured force and that predicted by Young's equation. 

PMID- 24033050
TI  - Experimental evidence for oxygen sublattice control in polar infinite layer
      SrCuO2.
AB  - A recent theoretical study [Phys. Rev. B 85, 121411(R) (2012)] predicted a
      thickness limit below which ideal polar cuprates turn nonpolar driven by the
      associated electrostatic instability. Here we demonstrate this possibility by
      inducing a structural transformation from the bulk planar to chainlike structure
      upon reducing the SrCuO2 repeat thickness in SrCuO2/SrTiO3 superlattices with
      unit-cell precision. Our results, based on structural investigation by x-ray
      diffraction and high resolution scanning transmission electron microscopy,
      demonstrate that the oxygen sublattice can essentially be built by design. In
      addition, the electronic structure of the chainlike structure, as studied by x
      ray absorption spectroscopy, shows the signature for preferential hole occupation
      in the Cu 3d(3z2-r2) orbital, which is different from the planar case.

PMID- 24033051
TI  - Unusual two-stage kinetics of ethylene adsorption on Si(100) unraveled by surface
      optical spectroscopy and Monte Carlo simulation.
AB  - The adsorption of ethylene on a Si(100)-2*1 surface in an ultrahigh vacuum has
      been monitored at room temperature by use of real-time surface differential
      reflectance spectroscopy, which clearly demonstrated that the adsorption follows
      a two-stage process. About half a monolayer is obtained for 1 L, while the second
      stage is much slower, yielding the complete monolayer for an exposure of ~400  L.
      The kinetics over the full range has been successfully reproduced by a Monte
      Carlo calculation. The key point of this two-stage adsorption kinetic lies in the
      reduced adsorption probability (by a factor of several hundreds) on the Si
      dimers, neighbors of dimers which have already reacted, with respect to the
      adsorption probability on isolated dimers. This new kind of adsorption kinetics,
      due to a repulsion between already adsorbed molecules and additional molecules
      impinging on the surface, makes it a textbook case for a "cooperative" adsorption
      process. 

PMID- 24033052
TI  - Intrinsic fluid interfaces and nonlocality.
AB  - We present results of an extensive molecular dynamics simulation of the structure
      and fluctuations of a liquid-gas interface, close to its triple point, in a
      system with cutoff Lennard-Jones interactions. The equilibrium density profile,
      averaged and (shape dependent) constrained intrinsic density profiles together
      with the fluctuations of the interfacial shape are extracted using an intrinsic
      sampling method. The correlation between fluctuations in the interfacial shape
      and in the intrinsic density show that the latter is not due to rigid
      translations of some underlying profile, as is most commonly assumed. Instead,
      over the whole range of wavelengths from the system size down to the molecular
      diameter, we see wave-vector dependent behavior in good agreement with a nonlocal
      interfacial Hamiltonian theory specifying the shape dependence of the intrinsic
      profiles. 

PMID- 24033053
TI  - Organization of strongly interacting directed polymer liquids in the presence of
      stringent constraints.
AB  - The impact of impenetrable obstacles on the energetics and equilibrium structure
      of strongly repulsive directed polymers is investigated. As a result of the
      strong interactions, regions of severe polymer depletion and excess are found in
      the vicinity of the obstacle, and the associated free-energy cost is found to
      scale quadratically with the average polymer density. The polymer-polymer
      interactions are accounted for via a sequence of transformations: from the 3D
      line liquid to a 2D fluid of Bose particles to a 2D composite fermion fluid and,
      finally, to a 2D one-component plasma. The results presented here are applicable
      to a range of systems consisting of noncrossing directed lines. 

PMID- 24033054
TI  - Nonpareil Yb behavior in YbMn6Ge(6-x)Sn(x).
AB  - We investigate the temperature dependence of the Yb valence in YbMn6Ge1.8Sn4.2
      and YbMn6Ge1.6Sn4.4 using resonant inelastic x-ray scattering experiments. Yb is
      found to be in an intermediate valent state in the whole investigated temperature
      range (10-450 K). We thus prove that the unusually high magnetic ordering
      temperature of Yb (~60 and 90 K for x=4.2 and 4.4, respectively) involves an
      intermediate valent Yb, an unprecedentedly observed phenomenon. Further, an
      anomalous increase in the Yb valence is observed upon cooling. A scenario is
      proposed to explain this unusual behavior. It is based on the presence of
      magnetically ordered Mn moments and on an Anderson Hamiltonian with a Zeeman term
      modeling the magnetic interactions.

PMID- 24033055
TI  - Carrier separation at dislocation pairs in CdTe.
AB  - Through the use of aberration corrected scanning transmission electron
      microscopy, the atomic configuration of CdTe intragrain Shockley partial
      dislocation pairs has been determined: Single Cd and Te columns are present at
      opposite ends of both intrinsic and extrinsic stacking faults. These columns have
      threefold and fivefold coordination, indicating the presence of dangling bonds.
      Counterintuitively, density-functional theory calculations show that these
      dislocation cores do not act as recombination centers; instead, they lead to
      local band bending that separates electrons and holes and reduces undesirable
      carrier recombination. 

PMID- 24033056
TI  - Evidence for short-range-ordered charge stripes far above the charge-ordering
      transition in La1.67Sr0.33NiO4.
AB  - The temperature evolution of structural effects associated with charge order (CO)
      and spin order in La1.67Sr0.33NiO4 has been investigated using neutron powder
      diffraction. We report an anomalous shrinking of the c/a lattice parameter ratio
      that correlates with T(CO). The sign of this change can be explained by the
      change in interlayer Coulomb energy between the static-stripe-ordered state and
      the fluctuating-stripe-ordered state or the charge-disordered state. In addition,
      we identify a contribution to the mean-square displacements of Ni and in-plane O
      atoms whose width correlates quite well with the size of the pseudogap extracted
      from the reported optical conductivity, with a non-Debye-like component that
      persists below and well above T(CO). We infer that dynamic charge-stripe
      correlations survive to T~2T(CO).

PMID- 24033057
TI  - Phase space for the breakdown of the quantum Hall effect in epitaxial graphene.
AB  - We report the phase space defined by the quantum Hall effect breakdown in polymer
      gated epitaxial graphene on SiC (SiC/G) as a function of temperature, current,
      carrier density, and magnetic fields up to 30 T. At 2 K, breakdown currents
      (I(c)) almost 2 orders of magnitude greater than in GaAs devices are observed.
      The phase boundary of the dissipationless state (rho(xx)=0) shows a [1-(T/T(c))2]
      dependence and persists up to T(c)>45  K at 29 T. With magnetic field I(c) was
      found to increase ?B(3/2) and T(c)?B2. As the Fermi energy pproaches the Dirac
      point, the nu=2 quantized Hall plateau appears continuously from fields as low as
      1 T up to at least 19 T due to a strong magnetic field dependence of the carrier
      density.

PMID- 24033058
TI  - Anisotropic electronic state via spontaneous phase separation in strained
      vanadium dioxide films.
AB  - We resolved the enigma of anisotropic electronic transport in strained vanadium
      dioxide (VO2) films by inquiring into the role that strain plays in the nanoscale
      phase separation in the vicinity of the insulator-to-metal transition. The root
      source of the anisotropy was visualized as the formation of a peculiar
      unidirectional stripe state which accompanies the phase transition. Furthermore,
      nanoscale infrared spectroscopy unveils distinct facets of electron-lattice
      interplay at three different stages of the phase transition. These stages include
      the initial formation of sparse nonpercolating metallic domains without
      noticeable involvement of the lattice followed by an electron-lattice coupled
      anisotropic stripe state close to percolation which ultimately evolves into a
      nearly isotropic rutile metallic phase. Our results provide a unique mesoscopic
      perspective for the tunable macroscopic phenomena in strained metal oxide films.

PMID- 24033059
TI  - Localized many-particle Majorana modes with vanishing time-reversal symmetry
      breaking in double quantum dots.
AB  - We introduce the concept of spinful many-particle Majorana modes with local odd
      operator products, thereby preserving their local statistics. We consider a
      superconductor-double-quantum-dot system where these modes can arise with
      negligible Zeeman splitting when Coulomb interactions are present. We find a
      reverse Mott-insulator transition, where the even- and odd-parity bands become
      degenerate. Above this transition, Majorana operators move the system between the
      odd-parity ground state, associated with elastic cotunneling, and the even-parity
      ground state, associated with crossed Andreev reflection. These Majorana modes
      are described in terms of one, three, and five operator products. Parity
      conservation results in a 4pi periodic supercurrent in the even state and no
      supercurrent in the odd state. 

PMID- 24033060
TI  - Ultrahigh magnetic field study of layer split bands in graphite.
AB  - We report studies of the magnetospectroscopy of graphite into a new regime of
      high energies and ultrahigh magnetic fields which allows us to perform the first
      spectroscopic studies of the interlayer split-off bands, E1 and E2. These bands
      can be well described by an asymmetric bilayer model and have only a small
      interlayer band gap asymmetry. We show that all of the properties of the
      electrons and holes can be described by a simple relativistic behavior determined
      by gamma0 and gamma1.

PMID- 24033061
TI  - Spatially separated spin carriers in spin-semiconducting graphene nanoribbons.
AB  - A graphene nanoribbon with sawtooth edges has a ferromagnetic ground state. Using
      first-principles and tight-binding model calculations, we show that, under a
      transverse electrical field, the sawtooth graphene nanoribbons become a spin
      semiconductor whose charge carriers are not only spin polarized in energy space
      but also spatially separated at different edges. Low-energy excitation produces
      spin-up electrons localized at one edge and spin-down holes at the opposite edge,
      and the excitation energy of spin carries can be tuned by the electric field to
      reach a new state of spin gapless semiconductor. Also, the spin semiconducting
      states are shown to be robust against at least 10% edge disorder. These features
      demonstrate a good tunability of spin carriers for spintronics applications. 

PMID- 24033062
TI  - Model evidence of an anisotropic chiral d+id-wave pairing state for the water
      intercalated Na(x)CoO2.yH2O superconductor.
AB  - Since its discovery, the superconducting phase in water-intercalated sodium
      cobaltates Na(x)CoO2.yH2O (x~0.3, y~1.3) has posed fundamental challenges in
      terms of experimental investigation and theoretical understanding. By a combined
      cluster calculation and renormalization group approach, we find an anisotropic
      chiral d+id-wave state as a consequence of multiorbital effects, Fermi surface
      topology, and magnetic fluctuations. It naturally explains the singlet property
      and close-to-nodal gap features of the superconducting phase as indicated by
      experiments.

PMID- 24033063
TI  - Detection of antiferromagnetic ordering in heavily doped LaFeAsO(1-x)H(x)
      pnictide superconductors using nuclear-magnetic-resonance techniques.
AB  - We studied double superconducting (SC) domes in LaFeAsO(1-x)H(x) by using 75As
      and 1H nuclear-magnetic-resonance techniques and unexpectedly discovered that a
      new antiferromagnetic (AF) phase follows the double SC domes on further H doping,
      forming a symmetric alignment of AF and SC phases in the electronic phase
      diagram. We demonstrated that the new AF ordering originates from the nesting
      between electron pockets, unlike the nesting between electron and hole pockets,
      as seen in the majority of undoped pnictides. The new AF ordering is derived from
      the features common to high-Tc pnictides; however, it has not been reported so
      far for other high-Tc pnictides because of their poor electron doping capability.

PMID- 24033064
TI  - Spin-orbital coupling in a triplet superconductor-ferromagnet junction.
AB  - We study the interplay of spin and orbital degrees of freedom in a triplet
      superconductor-ferromagnet junction. Using a self-consistent spatially dependent
      mean-field theory, we show that increasing the angle between the ferromagnetic
      moment and the triplet vector order parameter enhances or suppresses the p-wave
      gap close to the interface, according to whether the gap antinodes are parallel
      or perpendicular to the boundary, respectively. The associated change in
      condensation energy establishes an orbitally dependent preferred orientation for
      the magnetization. When both gap components are present, as in a chiral
      superconductor, first-order transitions between different moment orientations are
      observed as a function of the exchange field strength. 

PMID- 24033066
TI  - Excitation spectra of disordered dimer magnets near quantum criticality.
AB  - For coupled-dimer magnets with quenched disorder, we introduce a generalization
      of the bond-operator method, appropriate to describe both singlet and
      magnetically ordered phases. This allows for a numerical calculation of the
      magnetic excitations at all energies across the phase diagram, including the
      strongly inhomogeneous Griffiths regime near quantum criticality. We apply the
      method to the bilayer Heisenberg model with bond randomness and characterize both
      the broadening of excitations and the transfer of spectral weight induced by
      disorder. Inside the antiferromagnetic phase this model features the remarkable
      combination of sharp magnetic Bragg peaks and broad magnons, the latter arising
      from the tendency to localization of low-energy excitations. 

PMID- 24033065
TI  - Identifying the electronic character and role of the Mn states in the valence
      band of (Ga,Mn)As.
AB  - We report high-resolution hard x-ray photoemission spectroscopy results on
      (Ga,Mn)As films as a function of Mn doping. Supported by theoretical calculations
      we identify, for both low (1%) and high (13%) Mn doping values, the electronic
      character of the states near the top of the valence band. Magnetization and
      temperature-dependent core-level photoemission spectra reveal how the delocalized
      character of the Mn states enables the bulk ferromagnetic properties of
      (Ga,Mn)As. 

PMID- 24033067
TI  - Self-organized criticality in glassy spin systems requires a diverging number of
      neighbors.
AB  - We investigate the conditions required for general spin systems with frustration
      and disorder to display self-organized criticality, a property which so far has
      been established only for the fully connected infinite-range Sherrington
      Kirkpatrick Ising spin-glass model [Phys. Rev. Lett. 83, 1034 (1999)]. Here, we
      study both avalanche and magnetization jump distributions triggered by an
      external magnetic field, as well as internal field distributions in the short
      range Edwards-Anderson Ising spin glass for various space dimensions between 2
      and 8, as well as the fixed-connectivity mean-field Viana-Bray model. Our
      numerical results, obtained on systems of unprecedented size, demonstrate that
      self-organized criticality is recovered only in the strict limit of a diverging
      number of neighbors and is not a generic property of spin-glass models in finite
      space dimensions. 

PMID- 24033068
TI  - Unveiling the physics of the doped phase of the t - J model on the kagome
      lattice.
AB  - We investigate the ground state properties of the kagome lattice t - J model at
      low doping by variational Monte Carlo calculations. The resulting state possesses
      an interesting balance of spin exchange and kinetic exchange through the building
      blocks of stars which are linked by triangles and their internal hexagons. While
      the spin exchange is taking place mainly on the stars, hopping is favored on the
      hexagons. There is a density modulation, resulting in the holes having an
      effective static contribution. From this observation, how holes lead to
      dimerization in this model and why a particular valence bond crystal pattern is
      formed can be understood. Furthermore, we argue the optimal doping for this
      state. We discuss our result in connection with static impurities, and show the
      likely relevance to the diluted kagome lattice Heisenberg model, describing
      actual compounds.

PMID- 24033069
TI  - Reversal of the lattice structure in SrCoO(x) epitaxial thin films studied by
      real-time optical spectroscopy and first-principles calculations.
AB  - Using real-time spectroscopic ellipsometry, we directly observed a reversible
      lattice and electronic structure evolution in SrCoO(x) (x=2.5-3) epitaxial thin
      films. Drastically different electronic ground states, which are extremely
      susceptible to the oxygen content x, are found in the two topotactic phases:
      i.e., the brownmillerite SrCoO2.5 and the perovskite SrCoO3. First-principles
      calculations confirmed substantial differences in the electronic structure,
      including a metal-insulator transition, which originate from the modification in
      the Co valence states and crystallographic structures. More interestingly, the
      two phases can be reversibly controlled by changing the ambient pressure at
      greatly reduced temperatures. Our finding provides an important pathway to
      understanding the novel oxygen-content-dependent phase transition uniquely found
      in multivalent transition metal oxides.

PMID- 24033070
TI  - Electronic structure of spinel-type nitride compounds Si3N4, Ge3N4, and Sn3N4
      with tunable band gaps: application to light emitting diodes.
AB  - In this Letter using experimental and theoretical methods, we show that the solid
      solutions of group 14 nitrides having spinel structure (gamma-M3N4 where M=Si,
      Ge, Sn) exhibit mainly direct electronic band gaps with values that span the
      entire visible wavelength region, making these hard and thermally stable
      materials suitable for optoelectronic devices and, in particular, lighting
      applications. Using the simulated band structure, we also calculate the exciton
      binding energy. The combination of large exciton binding energies and the tunable
      electronic band gaps in the visible range makes these binary spinel nitrides and
      their solid solutions a new class of multifunctional materials with
      optoelectronic properties that can be engineered to suit the desired application.

PMID- 24033071
TI  - Ferroelectric phase transitions in small particles and local regions.
AB  - Phase transitions in spherical particles of a cubic ferroelectric are considered
      within Landau-Ginzburg-Devonshire theory. Concentrating on effects of the
      depolarizing field, we study competition between states with homogeneous
      polarization and vortex structures. For large radii of the sphere (R>Rc), the
      phase transition is into a vortex state while for R<Rc it might be into an
      homogeneous state. Rc is proportional to the square root of the dielectric
      constant of the environment. If this constant is of the order of unity, a
      transition into homogeneous state is practically impossible. The obtained results
      are applied to a discussion of the formation of "polar nanoclusters" in relaxors.

PMID- 24033072
TI  - Spin pumping and enhanced Gilbert damping in thin magnetic insulator films.
AB  - Precessing magnetization in a thin-film magnetic insulator pumps spins into
      adjacent metals; however, this phenomenon is not quantitatively understood. We
      present a theory for the dependence of spin pumping on the transverse mode number
      and in-plane wave vector. For long-wavelength spin waves, the enhanced Gilbert
      damping for the transverse mode volume waves is twice that of the macrospin mode,
      and for surface modes, the enhancement can be ten or more times stronger. Spin
      pumping is negligible for short-wavelength exchange spin waves. We corroborate
      our analytical theory with numerical calculations in agreement with recent
      experimental results. 

PMID- 24033073
TI  - Two-dimensional melting under quenched disorder.
AB  - We study the influence of quenched disorder on the two-dimensional melting
      behavior of superparamagnetic colloidal particles, using both video microscopy
      and computer simulations of repulsive parallel dipoles. Quenched disorder is
      introduced by pinning a fraction of the particles to an underlying substrate. We
      confirm the occurrence of the Kosterlitz-Thouless-Halperin-Nelson-Young scenario
      and observe an intermediate hexatic phase. While the fluid-hexatic transition
      remains largely unaffected by disorder, the hexatic-solid transition shifts to
      lower temperatures with increasing disorder. This results in a significantly
      broadened stability range of the hexatic phase. In addition, we observe
      spatiotemporal critical(like) fluctuations, which are consistent with the
      continuous character of the phase transitions. Characteristics of first-order
      transitions are not observed. 

PMID- 24033074
TI  - Shear thickening in non-Brownian suspensions: an excluded volume effect.
AB  - Shear thickening appears as an increase of the viscosity of a dense suspension
      with the shear rate, sometimes sudden and violent at high volume fraction. Its
      origin for noncolloidal suspension with non-negligible inertial effects is still
      debated. Here we consider a simple shear flow and demonstrate that fluid inertia
      causes a strong microstructure anisotropy that results in the formation of a
      shadow region with no relative flux of particles. We show that shear thickening
      at finite inertia can be explained as an increase of the effective volume
      fraction when considering the dynamically excluded volume due to these shadow
      regions. 

PMID- 24033075
TI  - Eigenvalue spectra of modular networks.
AB  - A large variety of dynamical processes that take place on networks can be
      expressed in terms of the spectral properties of some linear operator which
      reflects how the dynamical rules depend on the network topology. Often, such
      spectral features are theoretically obtained by considering only local node
      properties, such as degree distributions. Many networks, however, possess large
      scale modular structures that can drastically influence their spectral
      characteristics and which are neglected in such simplified descriptions. Here, we
      obtain in a unified fashion the spectrum of a large family of operators,
      including the adjacency, Laplacian, and normalized Laplacian matrices, for
      networks with generic modular structure, in the limit of large degrees. We focus
      on the conditions necessary for the merging of the isolated eigenvalues with the
      continuous band of the spectrum, after which the planted modular structure can no
      longer be easily detected by spectral methods. This is a crucial transition point
      which determines when a modular structure is strong enough to affect a given
      dynamical process. We show that this transition happens in general at different
      points for the different matrices, and hence the detectability threshold can vary
      significantly, depending on the operator chosen. Equivalently, the sensitivity to
      the modular structure of the different dynamical processes associated with each
      matrix will be different, given the same large-scale structure present in the
      network. Furthermore, we show that, with the exception of the Laplacian matrix,
      the different transitions coalesce into the same point for the special case where
      the modules are homogeneous but separate otherwise. 

PMID- 24033076
TI  - Hepatosplenic T-cell lymphoma.

PMID- 24033077
TI  - Synthesis, structure, and cytotoxicity studies of some fungal isochromanes.
AB  - Ustusorane D and penicisochromans B-D are natural isochromans isolated from
      Aspergillus ustus 094102 and Penicillium sp. PSU-F40, respectively. Herein, we
      report the syntheses of (-)-ustusorane D and (+)-penicisochroman B and the
      structures of penicisochromans C and D. The relative configuration of natural
      ustusorane D and the absolute configuration of natural penicisochroman B were
      determined. Two plausible structures for penicisochroman C were evaluated through
      synthesis, but their 1H and 13C NMR data were not in agreement with those of the
      natural product. The structural revision and the determination of the absolute
      configuration of natural penicisochroman D were achieved. Structure-activity
      relationship studies of the synthetic compounds as well as a series of related
      isochromans indicated that the enone of the furanone moiety was essential for the
      cytotoxicity of these compounds toward HCT116 human colon cancer cells.
      Pseudodeflectusin, the related natural isochroman, suppressed cell growth and
      induced apoptosis in HCT116 cells.

PMID- 24033078
TI  - Acute fetal asphyxia after gastric rupture in a pregnant patient with a gastric
      band.
AB  - We report a 37-year-old primigravida with a gastric band who developed the
      clinical picture of abdominal pain, vomiting and regurgitation coexistent with a
      cardiotocogram with severe variable decelerations with absent variability at 33
      weeks' gestation. After partial improvement with gastric band enlargement, new
      aggravation of symptoms and recurrence of a pathological cardiotocogram led to an
      emergency cesarean section. Intraoperatively, hemoperitoneum from gastric rupture
      was verified and partial gastrectomy was performed. After bariatric surgery,
      pregnant women are at increased risk of gastrointestinal complications, which may
      need prompt and multidisciplinary diagnosis and management in order to avoid
      maternal-fetal morbidity and mortality.

PMID- 24033079
TI  - Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in
      humans: Lost in translation.

PMID- 24033080
TI  - Vaccine-associated enhanced respiratory disease does not interfere with the
      adaptive immune response following challenge with pandemic A/H1N1 2009.
AB  - The implications of sequential prime and challenge with mismatched influenza A
      viruses is a concern in mammals, including humans. We evaluated the ability of
      pigs affected with vaccine-associated enhanced respiratory disease (VAERD) to
      generate a humoral immune response against the heterologous challenge virus
      inciting the VAERD. Vaccinated and challenged (V/C) pigs were administered an
      inactivated swine delta-cluster H1N2 (MN08) vaccine with an HA similar to pre
      2009 seasonal human viruses and challenged with heterologous A(H1N1) pandemic
      2009 (H1N1pdm09). Vaccination induced MN08-specific hemagglutination inhibition
      (HI) antibody but not cross-reacting H1N1pdm09 HI antibody. However, vaccinated
      pigs demonstrated significantly higher post-challenge anti-H1N1pdm09 serum
      neutralizing (SN) antibodies at 14 and 21 days post inoculation (dpi) compared to
      nonvaccinated, challenged pigs (NV/C), indicating a priming effect of the
      vaccine. Serum and lung whole virus anti-H1N1pdm09 IgG ELISA antibodies in the
      vaccinated group were significantly higher than the challenge only pigs at all
      time points evaluated. Lung IgA ELISA antibodies to both antigens were detected
      at 2, 5, and 21 dpi in vaccine-primed pigs, contrasted against mucosal ELISA
      antibody responses detected only at 21 dpi in the naive-challenged group.
      Collectively, vaccine-primed pigs demonstrated a robust humoral immune response
      and elevated local adaptive cytokine levels, indicating VAERD does not adversely
      affect the induction of an immune response to challenge with heterologous virus
      despite the severe clinical disease and underlying lung pathology. Thus, original
      antigenic sin does not appear to be a component of VAERD.

PMID- 24033081
TI  - Invasive forb benefits from water savings by native plants and carbon
      fertilization under elevated CO2 and warming.
AB  - As global changes reorganize plant communities, invasive plants may benefit. We
      hypothesized that elevated CO2 and warming would strongly influence invasive
      species success in a semi-arid grassland, as a result of both direct and water
      mediated indirect effects. To test this hypothesis, we transplanted the invasive
      forb Linaria dalmatica into mixed-grass prairie treated with free-air CO2
      enrichment and infrared warming, and followed survival, growth, and reproduction
      over 4 yr. We also measured leaf gas exchange and carbon isotopic composition in
      L. dalmatica and the dominant native C3 grass Pascopyrum smithii. CO2 enrichment
      increased L. dalmatica biomass 13-fold, seed production 32-fold, and clonal
      expansion seven-fold, while warming had little effect on L. dalmatica biomass or
      reproduction. Elevated CO2 decreased stomatal conductance in P. smithii,
      contributing to higher soil water, but not in L. dalmatica. Elevated CO2 also
      strongly increased L. dalmatica photosynthesis (87% versus 23% in P. smithii), as
      a result of both enhanced carbon supply and increased soil water. More broadly,
      rapid growth and less conservative water use may allow invasive species to take
      advantage of both carbon fertilization and water savings under elevated CO2 .
      Water-limited ecosystems may therefore be particularly vulnerable to invasion as
      CO2 increases.

PMID- 24033083
TI  - Changes of urinary phospholipids in the chronic kidney disease patients.
AB  - OBJECTIVE: To evaluate whether urinary phospholipids could be regarded as
      biomarkers of chronic kidney disease. MATERIALS AND METHODS: Thirteen healthy
      volunteers and 26 consecutive chronic kidney disease patients were included.
      Urinary phospholipids were quantified by high-performance liquid chromatography
      coupled with electrospray ionization tandem mass spectrometry. RESULTS: Urinary
      phosphatidylcholines concentrations (PC 16:0/16:0, 16:0/22:3, 16:0/18:1 and
      16:0/18:2) were significantly higher both in glomerulonephritis group (all p <
      0.001) and in tubulointerstitial injury group (all p < 0.05) than in healthy
      control group. Meanwhile, sphingomyelin concentrations (SM 18:1/16:0 and
      18:1/18:0) in glomerulonephritis group were significantly higher than those in
      healthy control group (all p < 0.001). Urinary PCs and SMs were positively
      correlated with proteinuria but negatively correlated with serum albumin.
      Meanwhile, PCs were positively correlated with serum creatinine. CONCLUSION: Our
      work first demonstrated that urinary phospholipids might be biomarkers for the
      chronic kidney disease patients. Increased urinary phospholipids in chronic
      kidney disease patients might result from proteinuria, damaged kidney function or
      proteinuria induced hypoalbuminemia or lipotoxicity.

PMID- 24033082
TI  - The association between red blood cell and platelet transfusion and subsequently
      developing idiopathic pneumonia syndrome after hematopoietic stem cell
      transplantation.
AB  - BACKGROUND: Blood transfusions are common during hematopoietic stem cell
      transplantation (HSCT) and may contribute to lung injury. STUDY DESIGN AND
      METHODS: This study examined the associations between red blood cell (RBC) and
      platelet (PLT) transfusions and idiopathic pneumonia syndrome (IPS) among 914
      individuals who underwent myeloablative allogeneic HSCT between 1997 and 2001.
      Patients received allogeneic blood transfusions at their physicians' discretion.
      RBCs, PLTs, and a composite of "other" transfusions were quantified as the sum of
      units received each 7-day period from 6 days before transplant until IPS onset,
      death, or Posttransplant Day 120. RBC and PLT transfusions were modeled as
      separate time-varying exposures in proportional hazards models adjusted for IPS
      risk factors (age, baseline disease, irradiation dose) and other transfusions.
      Timing of PLT transfusion relative to myeloid engraftment and PLT ABO blood group
      (match vs. mismatch) were included as potential interaction terms. RESULTS:
      Patients received a median of 9 PLT and 10 RBC units. There were 77 IPS cases
      (8.4%). Each additional PLT unit transfused in the prior week was associated with
      16% higher IPS risk (hazard ratio, 1.16; 95% confidence interval, 1.09-1.23; p <
      0.001). Recent RBC and PLT transfusions were each significantly associated with
      greater risk of IPS when examined without the other; only PLT transfusions
      retained significance when both exposures were included in the model. The PLT
      association was not modified by engraftment or ABO mismatch. CONCLUSION: PLT
      transfusions are associated with greater risk of IPS after myeloablative HSCT.
      RBCs may also contribute; however, these findings need confirmation.

PMID- 24033084
TI  - Genetic polymorphism of KIR2DL4 (CD158d), a putative NK cell receptor for HLA-G,
      does not influence susceptibility to asthma.
AB  - Human leukocyte antigen (HLA)-G is upregulated on the bronchial epithelium of
      asthma patients and genetic polymorphism affecting expression of HLA-G has been
      reported to influence susceptibility to asthma. As the NK cell receptor KIR2DL4
      has been reported to induce interferon gamma (IFNgamma) secretion when ligated
      with HLA-G, we postulated that the 9A/10A genetic polymorphism of KIR2DL4 which
      influences receptor structure may influence susceptibility to asthma. KIR2DL4
      genotypes were determined in two cohorts of children (n = 219 and n = 1356) in
      whom total serum IgE, allergen-specific IgE, atopy, bronchial reactivity and
      asthma symptoms had been studied between birth and 14 years. No reproducible
      associations with KIR2DL4 genotype were identified, leading us to conclude that
      the KIR2DL4 9A/10A polymorphism has no influence on susceptibility to asthma.

PMID- 24033085
TI  - Exercise as a therapeutic tool to prevent mitochondrial degeneration in
      nonalcoholic steatohepatitis.
AB  - Nonalcoholic fatty liver disease, encompassing hepatic steatosis, nonalcoholic
      steatohepatitis (NASH), fibrosis and cirrhosis, is a significant health problem
      associated with modern lifestyle, based on caloric overconsumption and physical
      inactivity. Although the mechanisms associated with progression from the 'benign'
      steatosis to NASH are still elusive, mitochondrial dysfunction seems to play an
      important role in this degenerative process. Degeneration of mitochondrial
      function during NASH has been associated with impaired beta-oxidation, oxidative
      phosphorylation and increased reactive oxygen species production, contributing to
      hepatocyte death and inflammatory response. Despite the fact that several
      therapeutic approaches can be used in the context of NASH, including insulin
      sensitizing agents, anti-obesity drugs, lipid-lowering drugs or mitochondrial
      targeted drugs, dietary and physical activity are still the most effective
      strategies. In fact, active lifestyles decrease insulin resistance and body
      weight and result in decreased histological signs of liver injury. In fatty
      liver, physical activity prevents the disease progression through mitochondrial
      adaptations, namely by increasing cytochrome c content, enzyme activities and
      fatty acid oxidation, which are lost after some days of physical inactivity.
      However, less is known about the effect of physical activity on NASH-associated
      mitochondrial dysfunction. After a brief characterization of NASH and its
      association with liver mitochondrial (dys)function, the present review addresses
      the impact of physical (in)activity on NASH and, particularly, the possible
      contribution of active lifestyles to the modulation of liver mitochondrial
      dysfunction. 

PMID- 24033086
TI  - Layer-by-layer polymer coating on discrete particles of cubic lyotropic liquid
      crystalline dispersions (cubosomes).
AB  - Cubic phase lyotropic liquid crystalline colloidal dispersions (cubosomes) were
      surface-modified with seven polyelectrolyte layers using a layer-by-layer (LbL)
      approach. The first layer consisted of a copolymer synthesized from methacrylic
      acid and oleoyl methacrylate for enhanced incorporation within the bilayer of the
      cubic nanostructure. Six additional layers of poly(L-lysine) and poly(methacrylic
      acid) were then sequentially added, followed by a washing procedure to remove
      polymer aggregates from the soft matter particles. Polymer buildup was monitored
      via microelectrophoresis, dynamic light scattering, and small-angle X-ray
      scattering. Polymer-coated cubosomes were observed with cryo-transmission
      electron microscopy. A potential application of the modified nanostructured
      particles presented in this study is to reduce the burst-release effect
      associated with drug-loaded cubosomes. The effectiveness of this approach was
      demonstrated through loading and release results from a model hydrophilic small
      molecule (fluorescein).

PMID- 24033087
TI  - Establishment of lipiodol as a fertility treatment - prospective study of the
      complete innovative treatment data set.
AB  - BACKGROUND: Our randomised controlled trial (RCT) found that a
      hysterosalpingogram (HSG) with the oil-soluble contrast medium (OSCM) lipiodol
      improves pregnancy rates amongst couples with unexplained and endometriosis
      related infertility. These results were supported by the findings of our
      observational study of the first 100 women to undergo the procedure after it was
      offered as an innovative treatment in New Zealand from September 2003. AIM: To
      further assess the safety and efficacy of lipiodol procedures and present
      together the complete data set of the procedures performed in our RCT and those
      performed as innovative procedures (n = 296) prior to it being offered as a
      standard fertility treatment. METHODS: Women with infertility underwent a
      therapeutic lipiodol procedure by HSG technique with fluoroscopy X-ray screening.
      Primary outcomes were clinical pregnancy within six months of the procedure and
      live birth. RESULTS: The overall pregnancy rate for the 296 women was 40.2%. The
      live birth/ongoing pregnancy rate was 31.4%. The pregnancy rates for women under
      the age of 40 with endometriosis and unexplained infertility were 51.1 and 31.4%,
      respectively. CONCLUSION: Lipiodol can now be considered a standard treatment for
      both unexplained and endometriosis-related infertility. The precise mechanism
      behind the fertility-enhancing effect of lipiodol has yet to be elucidated. This
      study supports a mechanism of effect on the endometrium with possible enhanced
      receptivity of the endometrium to embryo implantation.

PMID- 24033088
TI  - Non-irradiated female survivors of childhood acute lymphoblastic leukaemia are at
      risk of long-term increases in weight and body mass index.
AB  - We report long-term, including final height, auxological data from our
      retrospective study of non-irradiated survivors of childhood acute lymphoblastic
      leukaemia (ALL). Body mass index (BMI) standard deviation score (SDS) increases
      in females, due to increased weight-SDS, persisted to final height, with probable
      adverse long-term health outcomes. In contrast, males demonstrated increased BMI
      SDS in follow-up, due to reduced height-SDS, not increased weight-SDS, but such
      changes had resolved by final height. Childhood ALL survivors, particularly
      females, are therefore at potential increased risk of developing the metabolic
      syndrome during follow-up. We recommend that strategies to minimize weight gain
      should be implemented during ALL treatment. 

PMID- 24033089
TI  - Oral administration of alkaloid fraction from Ruta graveolens inhibits oxidative
      stress and inflammation in hypercholesterolemic rabbits.
AB  - CONTEXT: The anti-atherogenic effect of alkaloid fraction from Ruta graveolens
      Linn (Rutaceae) extract is suspected to be related to its activities of
      antioxidation and anti-inflammation. OBJECTIVE: This study investigated the
      efficacy of alkaloid fraction isolated from Ruta graveolens (AFR) in reducing
      oxidative damage and inflammation in hypercholesteremic rabbits. MATERIALS AND
      METHODS: The New Zealand white rabbits were randomly divided into three groups:
      Group I rabbits were fed with normal chow diet for 90 d. Group II rabbits were
      fed with 1% cholesterol-enriched diet. Group III rabbits were fed with 1%
      cholesterol-enriched diet together with AFR (10 mg/kg/daily for 90 d). RESULTS
      AND DISCUSSION: The results showed that on treatment with AFR significantly
      lowered the level of total cholesterol and LDL-C and showed an increment in the
      level of HDL-C. LD50 of the AFR in rats is greater than 525 mg/kg. Activities of
      antioxidant enzymes such as superoxide dismutase, catalase and glutathione
      peroxidase and GSH level were decreased in cholesterol-fed rabbit and
      supplementation of AFR significantly enhanced the activities of these antioxidant
      enzymes and GSH level. Increased activities of enzymes such as cyclooxygenase-2,
      15-lipoxygenase and myeloperoxidase were significantly suppressed by AFR
      administration. The acute phase proteins, total WBC count and TBARS
      concentrations were significantly increased by hypercholesteromic diet, which
      were significantly decreased by AFR treatment. Histopathological studies of aorta
      in cholesterol-fed rabbit showed plaque formation and significant changes in
      aortic wall. Administration of AFR showed no changes in aortic wall. CONCLUSION:
      AFR reduces oxidative stress and inflammation and reduces the aortic pathology in
      hypercholesteromic rabbits.

PMID- 24033090
TI  - Preservation of cell viability and protein conformation on immobilization within
      nanofibers via electrospinning functionalized yeast.
AB  - We investigate the immobilization of a model system of functionalized yeast that
      surface-display enhanced green fluorescent protein (eGFP) within chemically
      crosslinked polyvinyl alcohol (PVA) nanofibers. Yeast is incorporated into water
      insoluble nanofibrous materials by direct electrospinning with PVA followed by
      vapor phase chemical crosslinking of the polymer. Incorporation of yeast into the
      fibers is confirmed by elemental analysis and the viability is indicated by
      live/dead staining. Following electrospinning and crosslinking, we confirm that
      the yeast maintains its viability as well as the ability to express eGFP in the
      correct conformation. This method of processing functionalized yeast may thus be
      a powerful tool in the direct immobilization of properly folded, active enzymes
      within electrospun nanofibers with potential applications in biocatalysis. 

PMID- 24033091
TI  - Prior preterm birth and maternal subclinical cardiovascular disease 4 to 12 years
      after pregnancy.
AB  - BACKGROUND: We considered that women with prior preterm birth (PTB) would have
      evidence of subclinical atherosclerosis, endothelial dysfunction, and arterial
      stiffness. METHODS: Four to 12 years after pregnancy, blood pressure and fasting
      lipids were analyzed, and women underwent evaluation, following standardized
      protocols, of carotid intima-media thickness (IMT), brachial flow-mediated
      dilation (FMD), and pulse wave velocity (PWV). Women with prior preterm (<37
      weeks, n=181) or term births (>= 37 weeks, n=306) were compared. Those with
      preeclampsia or term small-for-gestational-age (SGA) births were excluded.
      RESULTS: Women with a prior preterm vs. term birth had higher blood pressure, on
      average, and a more atherogenic lipid profile. They also had marginally higher
      IMT (0.579 standard error [SE] 0.005-vs. 0.567 [0.004] mm, p=0.06), adjusted for
      body size, demographics, and smoking. IMT differences were greater among those
      with non-preeclamptic-indicated PTB (0.034 mm, p=0.05) and PTB<34 weeks (0.024
      mm, p=0.04) compared to those with term births. These differences appeared to be
      explained in part by the atherogenic lipid elevations in women with preterm
      birth. Women with prior PTB<34 weeks tended to have lower FMD, but results were
      not statistically significant. PWV did not differ according to PTB. CONCLUSIONS:
      In the decade following pregnancy, women with non-preeclamptic-indicated PTB or
      PTB delivered before 34 weeks had higher blood pressure, atherogenic lipids, and
      IMT compared to women with term births. There may be subgroups of women with a
      prior PTB with excess cardiovascular risk that is detectable before overt
      clinical disease.

PMID- 24033092
TI  - The burden of uterine fibroids for African-American women: results of a national
      survey.
AB  - BACKGROUND: Uterine fibroids have a disproportionate impact on African-American
      women. There are, however, no data to compare racial differences in symptoms,
      quality of life, effect on employment, and information-seeking behavior for this
      disease. METHODS: An online survey was conducted by Harris Interactive between
      December 1, 2011 and January 16, 2012. Participants were U.S. women aged 29-59
      with symptomatic uterine fibroids. African-American women were oversampled to
      allow statistical comparison of this high-risk group. Bivariate comparison of
      continuous and categorical measures was based on the t-test and the Chi-squared
      test, respectively. Multivariable adjustment of risk ratios was based on log
      binomial regression. RESULTS: The survey was completed by 268 African-American
      and 573 white women. There were no differences between groups in education,
      employment status, or overall health status. African-American women were
      significantly more likely to have severe or very severe symptoms, including heavy
      or prolonged menses (RR=1.51, 95% CI 1.05-2.18) and anemia (RR=2.73, 95% CI 1.47
      5.09). They also more often reported that fibroids interfered with physical
      activities (RR=1.67, 95% CI 1.20-2.32) and relationships (RR=2.27, 95% CI 1.23
      4.22) and were more likely to miss days from work (RR=1.77, 95% CI 1.20-2.61).
      African-American women were more likely to consult friends and family (36 vs.
      22%, P=0.004) and health brochures (32 vs. 18%, P<0.001) for health information.
      Concerns for future fertility (RR=2.65, 95% CI 1.93-3.63) and pregnancy (RR=2.89,
      95% CI 2.11-3.97) following fibroid treatments were key concerns for black women.
      CONCLUSIONS: African-American women have more severe symptoms, unique concerns,
      and different information-seeking behavior for fibroids.

PMID- 24033093
TI  - Protein photochromism observed by ultrafast vibrational spectroscopy.
AB  - Photochromic proteins, such as Dronpa, are of particular importance in bioimaging
      and form the basis of ultraresolution fluorescence microscopy. The photochromic
      reaction involves switching between a weakly emissive neutral trans form of the
      chromophore (A) and its emissive cis anion (B). Controlling the rates of
      switching has the potential to significantly enhance the spatial and temporal
      resolution in microscopy. However, the mechanism of the switching reaction has
      yet to be established. Here we report a high signal-to-noise ultrafast transient
      infrared investigation of the photochromic reaction in the mutant Dronpa2, which
      exhibits facile switching behavior. In these measurements we excite both the A
      and B forms and observe the evolution in the IR difference spectra over hundreds
      of picoseconds. Electronic excitation leads to bleaching of the ground electronic
      state and instantaneous (subpicosecond) changes in the vibrational spectrum of
      the protein. The chromophore and protein modes evolve with different kinetics.
      The chromophore ground state recovers in a fast nonsingle-exponential relaxation,
      while in a competing reaction the protein undergoes a structural change. This
      results in formation of a metastable form of the protein in its ground electronic
      state (A'), which subsequently evolves on the time scale of hundreds of
      picoseconds. The changes in the vibrational spectrum that occur on the
      subnanosecond time scale do not show unambiguous evidence for either proton
      transfer or isomerization, suggesting that these low-yield processes occur from
      the metastable state on a longer time scale and are thus not the primary
      photoreaction. Formation of A', and further relaxation of this state to the cis
      anion B, are relatively rare events, thus accounting for the overall low yield of
      the photochemical reaction. 

PMID- 24033095
TI  - Agomelatine in depression.
AB  - INTRODUCTION: Agomelatine is a relatively new antidepressant with a mechanism of
      action that is different from other antidepressants: it is a melatonergic agonist
      and a 5-HT2C antagonist. It is an effective treatment for depression, with
      relatively mild side effects. It may be a valuable pharmacological alternative in
      the clinical approach on depression. AREAS COVERED: The literature about
      agomelatine has been comprehensively reviewed. Agomelatine's efficacy, safety and
      tolerability are reviewed based on the studies undertaken in patients with major
      depressive disorder (MDD) and bipolar disorder (BPD). EXPERT OPINION: Agomelatine
      has shown an antidepressant effect in preclinical models, and the results of a
      large-scale clinical trial program, conducted in MDD, indicate both an
      antidepressant activity and a favorable tolerability profile. Agomelatine has no
      discontinuation syndrome, sexual discomfort is rare, and it is generally weigh
      neutral. The drug appears to be relatively safe in case of overdose. However,
      some cases of elevated hepatic transaminases are reported during treatment. As
      agomelatine has a mechanism of action that differs from other agents, it may
      represent a valuable additional treatment option in those patients who do not
      respond fully or who do not tolerate the side effects of other antidepressants.

PMID- 24033096
TI  - Characterization of the novel HLA-DPA1*02:05 allele identified by sequence-based
      typing.
AB  - The novel HLA-DPA1*02:05 variant allele differs from the closest allele
      DPA1*02:02:02. 

PMID- 24033097
TI  - Extreme diversification of the mating type-high-mobility group (MATA-HMG) gene
      family in a plant-associated arbuscular mycorrhizal fungus.
AB  - Arbuscular mycorrhizal fungi (AMF) are important plant symbionts that have long
      been considered evolutionary anomalies because of their apparent long-term lack
      of sexuality, but recent explorations of available DNA sequence have challenged
      this notion by revealing the presence of homologues of fungal mating type-high
      mobility group (MATA-HMG) and core meiotic genes in these organisms. To obtain
      more insights into the sexual potential of AMF, homologues of MATA-HMGs were
      sought in the transcriptome of three AMF isolates, and their functional and
      evolutionary trajectories were studied in genetically divergent strains of
      Rhizophagus irregularis using conventional and quantitative PCR procedures. Our
      analyses revealed the presence of at least 76 homologues of MATA-HMGs in R.
      irregularis isolates. None of these was found to be surrounded by genes generally
      found near other known fungal mating type loci, but here we report the presence
      of a 9-kb-long region in the AMF R. irregularis harbouring a total of four tandem
      repeated MATA-HMGs; a feature that highlights a potentially elevated intragenomic
      diversity in this AMF species. The present study provides intriguing insights
      into the genome evolution of R. irregularis, and represents a stepping stone for
      understanding the potential of these fungi to undergo cryptic sex. 

PMID- 24033100
TI  - Supramolecular assemblies of amide-derived organogels featuring rigid pi
      conjugated phenylethynyl frameworks.
AB  - Organogels, being an important class of soft materials, have evolved to be one of
      the most attractive subjects bridging supramolecular chemistry and material
      sciences due to their structural diversity and associated physical properties.
      Myriad applications in fields such as optoelectronics, light harvesting,
      environmental science, and regenerative medicine are being envisaged.
      Supramolecular gels usually are formed through self-aggregation of small-molecule
      gelators to form entangled self-assembled fibrillar networks through a
      combination of non covalent interactions such as hydrogen bonding, pi-pi
      stacking, electrostatic forces, donor-acceptor interactions, metal coordination,
      solvophobic forces, and van der Waals interactions. This feature article
      discusses recent and current state of research on amide derived organogelators
      bearing rigid conjugated phenylethynyl building blocks. Selective examples from
      our works along with some closely related examples from literature have been
      highlighted to showcase the structural diversity and their potential applications
      in supramolecular chemistry and materials science. 

PMID- 24033099
TI  - Alveolar bone regeneration potential of a traditional Chinese medicine, Bu-Shen
      Gu-Chi-Wan, in experimental periodontitis.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the effect of
      a traditional Chinese medicine, Bu-Shen-Gu-Chi-Wan, on experimental periodontitis
      and bone regeneration in rat. MATERIAL AND METHODS: Sixty female Sprague-Dawley
      rats were divided equally into three groups: a healthy control group (Group N); a
      periodontitis group (Group P); and the Bu-Shen-Gu-Chi-Wan treatment group (Group
      T). A 0.2-mm wire was placed around the maxillary first molar and Porphyromonas
      gingivalis was injected into the gingival sulcus. Rats in different groups were
      administered 0.9% normal saline or Bu-Shen-Gu-Chi-Wan solution (4 g/kg of body
      weight, for three alternate days), and the animals were killed after 4 wk.
      Morphological analysis of alveolar bone rebuilding was performed using micro
      computed tomography (micro-CT) and stereomicroscopy, and the variation of
      inflammation in the periodontium was determined histologically. The serum levels
      of the proinflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis
      factor-alpha (TNF-alpha) and of the bone-turnover biomarkers pyridinoline cross
      linked carboxyterminal telopeptide of type I collagen (ICTP) and osteocalcin (OC)
      were determined using radioimmunoassays. RESULTS: After treatment with Bu-Shen-Gu
      Chi-Wan, there were significant decreases in the levels of IL-1beta, TNF-alpha,
      ICTP and OC and decreased inflammatory infiltration in the periodontal tissues of
      Group T. significant changes in alveolar bone volume and density were detected by
      micro-CT, but stereomicroscopy did not detect a significant improvement of
      alveolar bone height. CONCLUSION: The data of the present study suggest that the
      traditional Chinese medicine, Bu-Shen-Gu-Chi-Wan, has anti-inflammatory function
      in experimental periodontitis and may simultaneously improve alveolar bone
      remodeling.

PMID- 24033101
TI  - Antiproliferative cardiac glycosides from the latex of Antiaris toxicaria.
AB  - Phytochemical investigation of the latex of Antiaris toxicaria resulted in the
      isolation of 15 new [antiarosides J-X (1-15)] and 17 known cardiac glycosides.
      The effects of the cardiac glycosides on apoptosis and the expression of orphan
      nuclear receptor Nur77 were examined in human NIH-H460 lung cancer cells. Several
      of the cardiac glycosides induced apoptosis in lung cancer cells, which was
      accompanied by induction of Nur77 protein expression. Treatment of cancer cells
      with the cardiac glycosides resulted in translocation of the Nur77 protein from
      the nucleus to the cytoplasm and subsequent targeting to mitochondria. The
      results show that the cardiac glycosides exert their apoptotic effect through the
      Nur77-dependent apoptotic pathway. 

PMID- 24033098
TI  - Mechanisms governing the health and performance benefits of exercise.
AB  - Humans are considered among the greatest if not the greatest endurance land
      animals. Over the last 50 years, as the population has become more sedentary,
      rates of cardiovascular disease and its associated risk factors such as obesity,
      type 2 diabetes and hypertension have all increased. Aerobic fitness is
      considered protective for all-cause mortality, cardiovascular disease, a variety
      of cancers, joint disease and depression. Here, I will review the emerging
      mechanisms that underlie the response to exercise, focusing on the major target
      organ the skeletal muscle system. Understanding the mechanisms of action of
      exercise will allow us to develop new therapies that mimic the protective actions
      of exercise. 

PMID- 24033102
TI  - Guideline on the prevention of secondary central nervous system lymphoma: British
      Committee for Standards in Haematology.
AB  - The guideline group was selected to be representative of UK-based medical
      experts. Ovid MEDLINE, EMBASE and NCBI Pubmed were searched systematically for
      publications in English from 1980 to 2012 using the MeSH subheading 'lymphoma,
      CNS', 'lymphoma, central nervous system', 'lymphoma, high grade', 'lymphoma,
      Burkitt's', 'lymphoma, lymphoblastic' and 'lymphoma, diffuse large B cell' as
      keywords, as well as all subheadings. The writing group produced the draft
      guideline, which was subsequently revised by consensus by members of the Haemato
      oncology Task Force of the British Committee for Standards in Haematology (BCSH).
      The guideline was then reviewed by a sounding board of ~50 UK haematologists, the
      BCSH and the British Society for Haematology (BSH) Committee and comments
      incorporated where appropriate. The 'GRADE' system was used to quote levels and
      grades of evidence, details of which can be found in Appendix I. The objective of
      this guideline is to provide healthcare professionals with clear guidance on the
      optimal prevention of secondary central nervous system (CNS) lymphoma. The
      guidance may not be appropriate to patients of all lymphoma sub-types and in all
      cases individual patient circumstances may dictate an alternative approach.
      Acronyms are defined at time of first use. 

PMID- 24033103
TI  - Body Mass Index of First Nations youth in Ontario, Canada: influence of sleep and
      screen time.
AB  - INTRODUCTION: Prevalence rates of overweight and obesity in Canada have risen
      rapidly in the past 20 years. Concurrent with the obesity epidemic, sleep time
      and physical activity levels have decreased among youth. Aboriginal youth
      experience disproportionately high obesity prevalence but there is inadequate
      knowledge of contributing factors. This research aimed to examine sleep and
      screen time behavior and their relationship to Body Mass Index (BMI) in on
      reserve First Nations youth from Ontario, Canada. METHODS: This was an
      observational population-based study of cross-sectional design. Self-reported
      physical activity, screen time, and lifestyle information was collected from 348
      youth aged 10-18 years residing in five northern, remote First Nations
      communities and one southern First Nations community in Ontario, Canada, from
      October 2004 to June 2010. Data were collected in the school setting using the
      Waterloo Web-based Eating Behaviour Questionnaire. Based on self-reported height
      and weight, youth were classified normal (including underweight), overweight and
      obese according to BMI. Descriptive cross-tabulations and Pearson's chi2 tests
      were used to compare screen time, sleep habits, and physical activity across BMI
      categories. RESULTS: Participants demonstrated low levels of after-school
      physical activity, and screen time in excess of national guidelines. Overall,
      75.5% reported being active in the evening three or less times per week.
      Approximately one-quarter of the surveyed youth watched more than 2 hours of
      television daily and 33.9% spent more than 2 hours on the internet or playing
      video games. For boys, time using the internet/video games (p=0.022) was
      positively associated with BMI category, with a greater than expected proportion
      of obese boys spending more than 2 hours using the internet or video games daily
      (56.7%). Also for boys, time spent outside after school (p=0.033) was negatively
      associated with BMI category, with a lesser than expected proportion spending
      'most of the time' outside (presumably being active) after school. These
      relationships were not observed in girls. Adjusted standardized residuals suggest
      a greater than expected proportion of obese individuals had a television in their
      bedroom (66.7%) as compared with the rest of the population. CONCLUSIONS: The
      current study adds to the limited information about contributors to overweight
      and obesity in First Nations youth living on-reserve in Canada. Concerns about
      inadequate sleep, excess screen time, and inadequate physical activity mirror
      those of the general population. Further investigation is warranted to improve
      the understanding of how various lifestyle behaviors influence overweight,
      obesity, and the development of chronic disease among First Nations youth.
      Initiatives to reduce screen time, increase physical activity, and encourage
      adequate sleep among on-reserve First Nations youth are recommended.

PMID- 24033104
TI  - Expression, purification, and solid-state NMR characterization of the membrane
      binding heme protein nitrophorin 7 in two electronic spin states.
AB  - The nitrophorins (NPs) comprise a group of NO transporting ferriheme b proteins
      found in the saliva of the blood sucking insect Rhodnius prolixus . In contrast
      to other nitrophorins (NP1-4), the recently identified membrane binding isoform
      NP7 tends to form oligomers and precipitates at higher concentrations in
      solution. Hence, solid-state NMR (ssNMR) was employed as an alternative method to
      gain structural insights on the precipitated protein. We report the expression
      and purification of (13)C,(15)N isotopically labeled protein together with the
      first ssNMR characterization of NP7. Because the size of NP7 (21 kDa) still
      provides a challenge for ssNMR, the samples were reverse labeled with Lys and Val
      to reduce the number of crosspeaks in two-dimensional spectra. The two electronic
      spin states with S = 1/2 and S = 0 at the ferriheme iron were generated by the
      complexation with imidazole and NO, respectively. ssNMR spectra of both forms are
      well resolved, which allows for sequential resonance assignments of 22 residues.
      Importantly, the ssNMR spectra demonstrate that aggregation does not affect the
      protein fold. Comparison of the spectra of the two electronic spin states allows
      the determination of paramagnetically shifted cross peaks due to pseudocontact
      shifts, which assists the assignment of residues close to the heme center. 

PMID- 24033105
TI  - Expression of asparagine synthetase predicts in vitro response to L-asparaginase
      in canine lymphoid cell lines.
AB  - l-asparaginase (L-asp), a bacterial enzyme that depletes extracellular
      asparagine, is used to treat acute lymphoblastic leukemia in humans and a variety
      of aggressive lymphoid malignancies in dogs. Resistance to this drug is an
      important cause of treatment failure in both species. Using canine lymphoid cell
      lines, we found that L-asp sensitivity is strongly negatively correlated with the
      level of methylation of the asparagine synthetase (ASNS) promoter. Selection for
      in vitro resistance was accompanied by increased ASNS promoter methylation and
      decreased ASNS mRNA expression. In addition, treatment with the hypomethylating
      agent 5-azacytidine increased resistance to L-asp. ASNS methylation and
      expression is not predictive of overall survival or progression-free survival in
      canine lymphoma patients treated with L-asp. Our data suggest that ASNS is an
      important factor in mediating the in vitro response of canine lymphoid cells to L
      asp; however, resistance mechanisms may be more complex in dogs treated
      clinically with L-asp, potentially due to concurrent treatments.

PMID- 24033106
TI  - Case series of patients with acute myeloid leukemia receiving hypomethylation
      therapy and retrospectively found to have IDH1 or IDH2 mutations.

PMID- 24033107
TI  - Genetic polymorphism of tumor necrosis factor promoter region and susceptibility
      to develop Hodgkin lymphoma in a Mexican population.
AB  - Hodgkin lymphoma (HL) is a rare neoplasm of the lymphatic system, in which
      inflammation and allelic variants in cytokines have been proposed as etiological
      factors. Epstein-Barr virus infection is often associated as a risk factor in HL
      and since cytokines are involved in the humoral response to viral infection. Our
      aim was to study the association between single nucleotide polymorphisms (SNPs)
      located in the tumor necrosis factor (TNF) gene (- 376G> A, - 238G> A and 581G>
      A) in a sample of Mexican patients (56 cases) and their susceptibility to develop
      HL, comparing these SNPs among healthy individuals (127 controls). Frequencies
      for TNF - 238G> A and TNF 581G> A showed no significant differences between cases
      and controls. However, the proportion of cases with the GA genotype of - 376 SNP
      showed a significant difference as compared to controls, odds ratio = 4.41 (95%
      confidence interval: 1.21-16.6), p = 0.02. We found that in this group of
      patients from Mexico the SNP - 376G> A in TNF shows an association with higher
      risk for HL.

PMID- 24033108
TI  - Transition of idiopathic CD4 + lymphocytopenia into mycosis fungoides?

PMID- 24033109
TI  - Plasma cell neoplasm associated chronic neutrophilic leukemia with membrane
      proximal and truncating CSF3R mutations.

PMID- 24033110
TI  - Morphologic features of binucleated lymphocytes to assess the diagnosis of
      persistent B-cell polyclonal lymphocytosis or other mature B-cell neoplasms.
AB  - The observation of binucleated lymphocytes (BNLs) on a peripheral blood smear is
      essential to the diagnosis of persistent polyclonal B-cell lymphocytosis (PPBL).
      Only a few case reports have mentioned their presence in other contexts, mainly
      mature B-cell neoplasms such as chronic lymphocytic leukemia or reactive
      circumstances such as multiple sclerosis undergoing natalizumab treatment. We
      sought to investigate whether any particular morphologic features of BNL were
      more specific to PPBL than other diseases. We reviewed peripheral blood smears of
      a series of patients affected by PPBL or harboring BNLs whatever the diagnosis.
      We found that BNLs in PPBL were heterogeneous, but mostly medium-sized with a
      moderately abundant basophilic cytoplasm, sometimes vacuolated. The chromatin was
      mature in an asymmetrically bilobed nucleus showing one to two nucleoli. Though
      mainly observed in patients with PPBL, all these criteria remained non-specific.
      Conversely, the presence of either monocytoid or hyperbasophilic cells had
      clinical value to confirm PPBL. We conclude that a substantial percentage of BNLs
      possessing the morphologic features described and observed in a context of
      monocytoid and/or hyperbasophilic lymphocytes is predictive of the diagnosis of
      PPBL.

PMID- 24033111
TI  - Successful treatment with allogeneic hematopoietic stem cell transplant in a
      mature B-cell leukemia with MYC and BCL2 translocation.

PMID- 24033112
TI  - Rapid acceleration of ferrous iron/peroxymonosulfate oxidation of organic
      pollutants by promoting Fe(III)/Fe(II) cycle with hydroxylamine.
AB  - The reaction between ferrous iron (Fe(II)) with peroxymonosulfate (PMS) generates
      reactive oxidants capable of degrading refractory organic contaminants. However,
      the slow transformation from ferric iron (Fe(III)) back to Fe(II) limits its
      widespread application. Here, we added hydroxylamine (HA), a common reducing
      agent, into Fe(II)/PMS process to accelerate the transformation from Fe(III) to
      Fe(II). With benzoic acid (BA) as probe compound, the addition of HA into
      Fe(II)/PMS process accelerated the degradation of BA rapidly in the pH range of
      2.0-6.0 by accelerating the key reactions, including the redox cycle of
      Fe(III)/Fe(II) and the generation of reactive oxidants. Both sulfate radicals and
      hydroxyl radicals were considered as the primary reactive oxidants for the
      degradation of BA in HA/Fe(II)/PMS process with the experiments of electron spin
      resonance and alcohols quenching. Moreover, HA was gradually degraded to N2, N2O,
      NO2 (-), and NO3 (-), while the environmentally friendly gas of N2 was considered
      as its major end product in the process. The present study might provide a
      promising idea based on Fe(II)/PMS process for the rapid degradation of
      refractory organic contaminants in water treatment.

PMID- 24033113
TI  - Unexpected imidazoquinoxalinone annulation products in the photoinitiated
      reaction of substituted-3-methyl-quinoxalin-2-ones with N-phenylglycine.
AB  - Photoinduced electron transfer between N-phenylglycine (NPG) and electronically
      excited triplets of 7-substituted-3-methyl-quinoxalin-2-ones in acetonitrile
      generate the respective ion radical pair, where by decarboxylation the phenyl
      amino-alkyl radical, PhNHCH2*, is generated. This radical reacts with the 3
      methyl-quinoxalin-2-ones ground states, leading to the product 2. Other,
      unexpected, 7-substituted-1,2,3,3a-tetrahydro-3a-methyl-2-phenylimidazo[1,5
      a]quinoxalin-4(5H)-ones, annulation products, 3a-f, were generated; likely by the
      addition of two PhNHCH2* radicals, to positions 3 and 4 of the quinoxalin-2-ones.
      The reaction mechanism includes a photoinduced one electron transfer initiation
      step, propagation steps involving radical intermediates and NPG with radical
      chain termination steps that lead to the respective products 2a-f and 3a-f and
      NPG by-products. The proposed mechanism accounts for the strong dependency found
      for the initial photoconsumption quantum yields on the electron-withdrawing power
      of the substituent. Therefore, photolysis of common reactants widely used such as
      NPG and substituted quinoxalin-2-ones may provide a simple synthetic way to the
      unusual, unreported tetrahydro-imidazoquinoxalinones 3a-f.

PMID- 24033114
TI  - Preferential solvation in carbonyl-twisted PRODAN derivatives.
AB  - The Roses and Bosch model for preferential solvation is used to analyze the
      fluorescence behavior of two PRODAN derivatives in binary solvents with one or
      two protic components. The preferential solvation results suggest that the
      excited PRODAN derivatives form two H-bonds. The model allows for determining the
      characteristics of the singly H-bonded excited states. They show red-shifted
      fluorescence but relatively little quenching. In contrast, the doubly H-bonded
      excited states are significantly quenched when the protic solvent is a strong H
      bond donor (large SA value). With two protic solvents there is little
      preferential interaction even though the solvents have very different H-bond
      forming ability. 

PMID- 24033115
TI  - Stress and worry: examining intolerance of uncertainty's moderating effect.
AB  - Intolerance of uncertainty (IU), or the way an individual perceives, interprets,
      and reacts to uncertainty in life, has been frequently investigated in relation
      to anxiety and worry. While a substantial body of research suggests that
      individual differences in IU foster stress and anxiety, IU's involvement as a
      potential moderator in the relation between stressful events and worry has only
      recently been investigated. Therefore, the present study examined the moderating
      effect of IU on the relation between daily hassles and worry as well as major
      life events and worry in a sample of 1092 young adults. Results revealed that IU
      showed a significant moderation effect in the relation between daily stress and
      worry. More specifically, when the two factors were examined individually only
      inhibitory IU served as a moderator between daily stress and worry. While major
      life events significantly predicted worry, no moderation effect was found for
      this relation. These findings highlight the need to better understand the
      mechanisms through which IU impacts worry and contributes to anxiety. 

PMID- 24033116
TI  - Immune regulation of bone loss by Th17 cells in oestrogen-deficient osteoporosis.
AB  - BACKGROUND: The role of T helper (Th) 17 cells in autoimmune diseases has been
      extensively studied recently, but its function in oestrogen-deficient
      osteoporosis remains undefined. This review aimed to explore the role of Th17
      cells in regulating bone loss induced by oestrogen deficiency. MATERIALS AND
      METHODS: We searched PubMed, Embase, Google Scholar and Biosis up to 1 February
      2013 for immune regulation of oestrogen-deficient osteoporosis by Th17 cells.
      Terms relevant to immunity, oestrogen deficiency, osteoporosis and Th17 cells
      were used for database searching. Seventy-five papers met the predetermined
      searching criteria. RESULTS: Studies indicate Th17 lineage to be a potent
      osteoclastogenic mediator in oestrogen-deficient osteoporosis. Oestrogen
      deficiency promotes osteoclastogenesis by up-regulating Th17 cell populations in
      bone marrow and IL-17 levels in peripheral blood. Meanwhile, transcription
      factors involved in Th17 cell differentiation, such as RORgammat and RORalpha,
      are highly expressed in ovariectomized animals. Treatment with IL-17
      significantly promotes production of RANKL, TNF and IL-6 as well as TRAP(+) cells
      in culture; blocking IL-17 pathway significantly reduces abundance of Th17 cells
      and effectively prevents bone loss in ovariectomized mice. CONCLUSIONS: The main
      body of literatures suggests Th17 to be a critical modulator in the pathogenesis
      of oestrogen-deficient osteoporosis, which supports the notion that oestrogen
      deficient osteoporosis is a complex interplay between oestrogen, osteoclastogenic
      cytokines and osteoclasts. In addition, therapeutic strategies targeting IL-17
      networks may be clinically useful in treatment for postmenopausal osteoporosis.

PMID- 24033117
TI  - A stereologic study of the plantar fat pad in young and aged rats.
AB  - Plantar fat pad (PFP) is a tissue structure that absorbs the initial impact of
      walking and running and ultimately bears body weight at standing. This study was
      designed to quantify the histomorphological changes of the PFP in aged rats. The
      most medial PFP was dissected from the hind feet of young rats (4 months old, n =
      6) and aged rats (24 months old, n = 6). Histological structure and cellular
      senescence of PFP were analyzed stereologically and histomorphometrically.
      Immunohistochemistry of matrix metalloproteinase 9 (MMP9) was also performed on
      PFP tissue sections. Compared with young rats, the thickness of epidermis, dermis
      and septa of the PFP were significantly reduced in the aged rats. The total
      volume of adipose tissue in the PFP of aged rats was only about 65% of that in
      the young rats. The microvascular density and the number of fat pad units (FPU),
      a cluster of adipocytes enclosed by elastin septa, in the PFP were unchanged in
      the aged rats. In the aged rats, the number of adipocytes per FPU was reduced but
      the number of simple adipocyte clusters, without surrounding septa, was
      increased. The shift of the types of adipocyte clusters in the aged PFP was
      accompanied by degradation of elastin fibers and increased expression of MMP9. In
      conclusion, the PFP, particularly the elastic septa, degenerates significantly in
      aged rats and this may contribute to the pathology of PFP-related diseases. 

PMID- 24033118
TI  - Vulnerable infected populations and street markets for ARVs: Potential
      implications for PrEP rollout in the USA.
AB  - Widespread diversion of antiretroviral (ARV) medications to illicit markets has
      recently been documented among indigent patients in South Florida. The recent
      approval of ARVs for pre-exposure prophylaxis (PrEP) has the potential to broaden
      these illicit markets, as high-risk individuals seek ARVs without a prescription
      or medical supervision. Nonadherence among diverters and unsupervised use of ARVs
      for treatment or PrEP increase risks of treatment failure, drug resistance, and
      disease transmission. We report the scope of ARV diversion among substance-using
      men who have sex with men in South Florida. Structured interviews (N = 515)
      queried demographics, HIV status, mental distress, substance dependence, and
      sexual risks. HIV-positive participants answered questions about medical care,
      treatment, and ARV adherence and diversion. Median age was 39. Of 46.4% who were
      HIV-positive, 79.1% were prescribed ARVs. Of these, 27% reported selling/trading
      ARVs. Reasons for diversion were sharing/trading with friends, sale/trade for
      money/drugs, and sale/trade of unused medications. ARV diverters, compared to
      nondiverters, were more likely to be substance dependent (74.5% vs. 58.7%, p =
      0.046) and have traded sex for money/drugs (60.8% vs. 32.6%, p < 0.001), and less
      likely to be adherent to ARVs (54.9% vs. 73.9%, p = 0.012). ARV diversion should
      be a particular concern in communities of high-risk men who have sex with men as
      uninfected men in such communities are likely to benefit most from PrEP but
      unlikely to have access to PrEP and necessary ancillary services through the
      health-care system. The implications of diversion for increased risks of
      treatment failure, disease transmission, and PrEP failure should be carefully
      considered in developing policy and behavioral supports to scaling up treatment
      as prevention and PrEP. 

PMID- 24033119
TI  - Marine natural products: bryostatins in preclinical and clinical studies.
AB  - CONTEXT: Bryostatins represent an important group of pharmaceutically promising
      substances. These compounds are produced by commensal microorganisms naturally
      occurring in marine invertebrates, mainly in bryozoans. The most frequently
      investigated substance is bryostatin-1, which is a highly oxygenated macrolide
      with a polyacetate backbone. OBJECTIVE: The aim of this work was to summarize
      documented preclinical and clinical effects of bryostatin-class compounds.
      METHODS: A literature search was made of Medline and Web of Science databases in
      2012. RESULTS AND CONCLUSION: Our review showed that bryostatins are potent
      agonists of protein kinase C. In addition to this, their significant
      antineoplastic activity against several tumor types has also been established and
      described. Bryostatin's anticancer activity has been proved against various
      cancer types. Moreover, significant results have been achieved by using
      bryostatin-1 in combination with other therapies, including combination with
      vaccine testing. Concerning other important properties that bryostatins possess,
      their ability to sensitize some resistant cells to chemotherapy agents, or
      immunoactivity and further stimulating growth of new neural connections, and
      enhancing effect on long-term memory are worth mentioning. In particular, some
      new bryostatin analogs could represent potential therapeutic agent for the
      treatment of cancer and other diseases in future.

PMID- 24033120
TI  - Extranodal NK/T cell lymphoma, nasal type, presenting with meningeal infiltration
      in a Caucasian female.

PMID- 24033121
TI  - Prevalence of human papillomavirus in epithelial ovarian cancer tissue. A meta
      analysis of observational studies.
AB  - OBJECTIVE: The role of human papillomavirus (HPV) in the pathogenesis of ovarian
      cancer is controversial, and conflicting results have been published. We
      conducted a systematic review and meta-analysis to estimate the prevalence of HPV
      in epithelial ovarian cancer tissue. MATERIAL AND METHODS: Observational studies
      published until 4 March 2013 were identified in PubMed and Embase. We adhered to
      MOOSE guidelines and included 22 studies (case-control, cross-sectional studies).
      A pooled estimate of the HPV prevalence with corresponding 95% confidence
      interval (CI) was calculated based on a random effect model. In a meta-regression
      analysis we examined the contribution of different factors to heterogeneity.
      Furthermore, publication bias was evaluated. RESULTS: The pooled HPV prevalence
      in ovarian cancer tissue was 15.5%, but wide variation was found (0-66.7%). After
      stratification by geographical region, publication year, tissue type and method
      of HPV detection, we found that the prevalence of HPV varied most markedly by
      geographical area, the prevalence being 45.6% (95% CI, 31.0-60.3) in Asia, 18.5%
      (95% CI, 8.5-28.6) in Eastern Europe, 1.1% (95% CI, -1.6 to 3.8) in Western
      Europe and zero in North America. A meta-regression analysis revealed that the
      difference between geographical regions could not be explained by HPV detection
      method or type of tissue. CONCLUSIONS: Great geographical variation exists in HPV
      prevalence in ovarian cancer tissue, which is not explained by different HPV
      detection methods. The results suggest that HPV is unlikely to play an important
      role in Western European and American women, but cannot reject a role of HPV in
      other populations.

PMID- 24033122
TI  - Predicting blood donation maintenance: the importance of planning future
      donations.
AB  - BACKGROUND: Interventions to retain blood donors need to target the most
      influential and changeable factors. This study tested antecedents of three
      successive donation decisions. STUDY DESIGN AND METHODS: Participants were donors
      who had donated for the first time 1 year previous (n = 1018). Intention to
      continue donating, vasovagal reactions, deferral, anxiety, and planning failure
      were measured. Analyses distinguished between 1) those who registered for
      donation after questionnaire completion, versus those who did not; 2) those who
      did or did not register for donation a second time after questionnaire
      completion; and 3) those who did or did not register for donation a third time
      after questionnaire completion. RESULTS: Three logistic regression analyses
      showed that the first donation decision was influenced by intention (odds ratio
      [OR], 1.70; 95% confidence interval [CI], 1.30-2.21), number of donations made in
      the first year (OR, 2.35; 95% CI, 1.81-3.06), vasovagal reactions (OR, 0.92; 95%
      CI, 0.87-0.97), and planning failure (OR, 0.81; 95% CI, 0.70-0.95). The second
      donation decision was influenced by intention (OR, 1.44; 95% CI, 1.06-1.95) and
      planning failure (OR, 0.67; 95% CI, 0.57-0.78), while the third decision was
      influenced only by planning failure (OR, 0.85; 95% CI, 0.73-1.00). CONCLUSION:
      This indicates that for new donors, retention efforts should focus on the
      promotion of a positive intention and decreasing vasovagal reactions. However,
      decreasing planning failure could be an even better investment since planning
      seems to determine long-term retention.

PMID- 24033123
TI  - Trafficking of gold nanorods in breast cancer cells: uptake, lysosome maturation,
      and elimination.
AB  - Gold nanorods (AuNRs) have been largely investigated driven by their promising
      potentials in drug delivery, imaging, and photodynamic therapy because of their
      distinctive physicochemical properties. It is widely known that AuNRs can be
      taken up by different cells, however, the trafficking of the nanorods in cells
      are less known. In this work, the behaviors and fate of AuNRs in the human breast
      cancer cell line MDA-MB-231 were intensively probed by transmission electron
      microscopy (TEM) with detailed time resolution, together with induced couple
      plasmon mass spectroscopy (ICP-MS), confocal microscopy, Western blot, and cell
      viability assay. We reveal that AuNRs enter the classic lysosome maturation
      through endocytosis and are sequestered in the vesicular system even during cell
      division. AuNRs can escape from the lysosomes occasionally and the escaped AuNRs
      are recycled back into the lysosomal system through cytoprotective autophagy. The
      dilution of AuNRs in cells is mainly attributed to the cell division rather than
      exocytosis, because expelled AuNRs can be re-endocytosed by the cells. The
      feature of vesicular restriction guarantees other organelles such as mitochondria
      and nucleus are exempted from the direct exposure to AuNRs. 

PMID- 24033125
TI  - A hierarchical model for probabilistic independent component analysis of multi
      subject fMRI studies.
AB  - An important goal in fMRI studies is to decompose the observed series of brain
      images to identify and characterize underlying brain functional networks.
      Independent component analysis (ICA) has been shown to be a powerful
      computational tool for this purpose. Classic ICA has been successfully applied to
      single-subject fMRI data. The extension of ICA to group inferences in
      neuroimaging studies, however, is challenging due to the unavailability of a pre
      specified group design matrix. Existing group ICA methods generally concatenate
      observed fMRI data across subjects on the temporal domain and then decompose
      multi-subject data in a similar manner to single-subject ICA. The major
      limitation of existing methods is that they ignore between-subject variability in
      spatial distributions of brain functional networks in group ICA. In this article,
      we propose a new hierarchical probabilistic group ICA method to formally model
      subject-specific effects in both temporal and spatial domains when decomposing
      multi-subject fMRI data. The proposed method provides model-based estimation of
      brain functional networks at both the population and subject level. An important
      advantage of the hierarchical model is that it provides a formal statistical
      framework to investigate similarities and differences in brain functional
      networks across subjects, for example, subjects with mental disorders or
      neurodegenerative diseases such as Parkinson's as compared to normal subjects. We
      develop an EM algorithm for model estimation where both the E-step and M-step
      have explicit forms. We compare the performance of the proposed hierarchical
      model with that of two popular group ICA methods via simulation studies. We
      illustrate our method with application to an fMRI study of Zen meditation. 

PMID- 24033126
TI  - Fluorescence-excitation and emission spectra from LH2 antenna complexes of
      Rhodopseudomonas acidophila as a function of the sample preparation conditions.
AB  - The high sensitivity of optical spectra of pigment-protein complexes to
      temperature and pressure is well known. In the present study, we have
      demonstrated the significant influence of the environments commonly used in bulk
      and single-molecule spectroscopic studies at low temperatures on the LH2
      photosynthetic antenna complex from Rhodopseudomonas acidophila. A transfer of
      this LH2 complex from a bulk-buffer solution into a spin-coated polymer film
      results in a 189 cm(-1) blue shift of the B850 excitonic absorption band at 5 K.
      Within the molecular exciton model, the origin of this shift could be
      disentangled into three parts, namely to an increase of the local site energies,
      a contraction of the exciton band, and a decrease of the displacement energy.

PMID- 24033128
TI  - An inhibitor of oil body mobilization in Arabidopsis.
AB  - Fatty acid beta-oxidation is an essential process in many aspects of plant
      development, and storage oil in the form of triacylglycerol (TAG) is an important
      food source for humans and animals, for biofuel and for industrial feedstocks. In
      this study we characterize the effects of a small molecule, diphenyl
      methylphosphonate, on oil mobilization in Arabidopsis thaliana. Confocal laser
      scanning microscopy, transmission electron microscopy and quantitative lipid
      profiling were used to examine the effects of diphenyl methylphosphonate
      treatment on seedlings. Diphenyl methylphosphonate causes peroxisome clustering
      around oil bodies but does not affect morphology of other cellular organelles. We
      show that this molecule blocks the breakdown of pre-existing oil bodies resulting
      in retention of TAG and accumulation of acyl CoAs. The biochemical and phenotypic
      effects are consistent with a block in the early part of the beta-oxidation
      pathway. Diphenyl methylphosphonate appears to be a fairly specific inhibitor of
      TAG mobilization in plants and whilst further work is required to identify the
      molecular target of the compound it should prove a useful tool to interrogate and
      manipulate these pathways in a controlled and reproducible manner. 

PMID- 24033130
TI  - The relationship of HLA-class I derived leader peptide mismatch and renal
      function within the first 12 months post-renal transplant.

PMID- 24033127
TI  - Pharmacotherapeutics for substance-use disorders: a focus on dopaminergic
      medications.
AB  - INTRODUCTION: Illicit substance-use is a substantial public health concern,
      contributing over $150 billion in costs annually to Americans. A complex disease,
      a substance-use disorder affects neural circuits involved in reinforcement,
      motivation, learning and memory, and inhibitory control. AREAS COVERED: The
      modulatory influence of dopamine in mesocorticolimbic circuits contributes to
      encoding the primary reinforcing effects of substances and numerous studies
      suggest that aberrant signaling within these circuits contributes to the
      development of a substance-use disorder in some individuals. Decades of research
      focused on the clinical development of medications that directly target dopamine
      receptors has led to recent studies of agonist-like dopaminergic treatments for
      stimulant-use disorders and, more recently, cannabis-use disorder. Human studies
      evaluating the efficacy of dopaminergic agonist-like medications to reduce
      reinforcing effects and substance-use provide some insight into the design of
      future pharmacotherapy trials. A search of PubMed using specific brain regions,
      medications, and/or the terms 'dopamine', 'cognition', 'reinforcement',
      'cocaine', 'methamphetamine', 'amphetamine', 'cannabis',
      'treatment/pharmacotherapy', 'addiction/abuse/dependence' identified articles
      relevant to this review. EXPERT OPINION: Conceptualization of substance-use
      disorders and their treatment continues to evolve. Current efforts increasingly
      focus on a strategy fostering combination pharmacotherapies that target multiple
      neurotransmitter systems.

PMID- 24033129
TI  - How and why does the 5-HTTLPR gene moderate associations between maternal
      unresponsiveness and children's disruptive problems?
AB  - This study tested the 5-HTTLPR gene as a moderator in the relation between
      maternal unresponsiveness and child externalizing symptoms in a disadvantaged,
      predominantly Black sample of two hundred and one 2-year-old children and their
      mothers. Using a multimethod, prospective design, structural equation model
      analyses indicated that maternal unresponsiveness significantly predicted
      increases in externalizing symptoms 2 years later only for children possessing
      the LL genotype. Moderation was expressed in a "for better" or "for worse" form
      hypothesized in differential susceptibility theory. In examining why the risk
      posed by maternal unresponsiveness differed across the 5-HTTLPR polymorphism,
      mediated moderation analyses showed that children's angry reactivity to maternal
      negativity partly accounted for the greater susceptibility of homozygous L
      carriers to variations in maternal unresponsiveness. 

PMID- 24033131
TI  - Cytotoxic clerodane diterpenoids from the leaves and twigs of Casearia balansae.
AB  - Ten new clerodane diterpenoids (1-10), caseabalansins A-G, 18-epicaseabalansin A,
      2-epicaseabalansin B, and 2-epicaseabalansin C, one new triterpenoid, balansinone
      (11), and seven known diterpenoids (12-18) were obtained from the leaves and
      twigs of Casearia balansae. Compounds 1 and 2 are the first examples of clerodane
      diterpenoids with an oxygen bridge between C-2 and C-19, and compounds 5-7 are
      three new diterpenoid artifacts presumably formed during the extraction process.
      The structures of the new compounds were established on the basis of extensive
      spectroscopic data, and that of 11 was verified by single-crystal X-ray
      crystallographic analysis. Compound 15 showed cytotoxic activity against the
      tumor cell lines PC3, DU145, SKOV3, and A549 with IC50 values of 4.5, 4.3, 5.1,
      and 5.7 MUM, respectively. Compounds 1a, 2a, and 4 showed selective activity
      against PC3 tumor cells.

PMID- 24033132
TI  - Patient perceptions of second transplants in myeloma: impact on recruitment in
      the British Society of Blood and Marrow Transplantation/UK Myeloma Forum Myeloma
      X Relapse (Intensive) Trial.

PMID- 24033134
TI  - Boric acid inhibits alveolar bone loss in rats by affecting RANKL and
      osteoprotegerin expression.
AB  - BACKGROUND AND OBJECTIVE: The goal of the present study was to evaluate the
      effects of systemic boric acid on the levels of expression of RANKL and
      osteoprotegerin (OPG) and on histopathologic and histometric changes in a rat
      periodontitis model. MATERIAL AND METHODS: Twenty-four Wistar rats were divided
      into three groups of eight animals each: nonligated (NL); ligature only (LO); and
      ligature plus treatment with boric acid (BA) (3 mg/kg per day for 11 d). A 4/0
      silk suture was placed in a subgingival position around the mandibular right
      first molars; after 11 d the rats were killed, and alveolar bone loss in the
      first molars was histometrically determined. Periodontal tissues were examined
      histopathologically to assess the differences among the study groups. RANKL and
      OPG were detected immunohistochemically. RESULTS: Alveolar bone loss was
      significantly higher in the LO group than in the BA and NL groups (p < 0.05). The
      number of inflammatory infiltrate and osteoclasts in the LO group was
      significantly higher than that in the NL and BA groups (p < 0.05). The numbers of
      osteoblasts in LO and BA groups were significantly higher compared with NL group
      (p < 0.05). There were significantly more RANKL-positive cells in the LO group
      than in the BA and NL groups (p < 0.05). There was a higher number of OPG
      positive cells in the BA group than in the LO and NL groups (p < 0.05).
      CONCLUSION: The present study shows that systemic administration of boric acid
      may reduce alveolar bone loss by affecting the RANKL/OPG balance in periodontal
      disease in rats.

PMID- 24033135
TI  - Carbon-dot-loaded alginate gels as recoverable probes: fabrication and mechanism
      of fluorescent detection.
AB  - We prepare a solid and green film of carbon-dot-loaded alginate gels with a pore
      structure. Compared to carbon dot suspension, the film exhibits stronger blue
      light emission. The porous structure of the film enables ion diffusion and
      contact with the CDs incorporated in the gel network, and thus the
      photoluminescence (PL) behavior of the film can be influenced by ions. The PL of
      the film shows a sensitive and selective quenching effect to Cu(2+), and it can
      be repeatedly used as a fluorescent probe to recognize Cu(2+) with a detection
      limit of 5 ppm. A band bending mechanism is proposed to understand the effects of
      surface/interface states and metal ions on the PL behavior of carbon-dot-loaded
      alginate gels, and it has been supported by our further experimental results.
      This band bending mechanism provides a clear physical insight into ion detection
      by PL behavior. 

PMID- 24033133
TI  - Conformational features of tau fibrils from Alzheimer's disease brain are
      faithfully propagated by unmodified recombinant protein.
AB  - Fibrils composed of tau protein are a pathological hallmark of several
      neurodegenerative disorders including Alzheimer's disease (AD). Here we show that
      when recombinant tau protein is seeded with paired helical filaments (PHFs)
      isolated from AD brain, the amyloid formed shares many of the structural features
      of AD PHFs. In contrast, tau amyloids formed with heparin as an inducing agent-a
      common biochemical model of tau misfolding-are structurally distinct from brain
      derived PHFs. Using ultrastructural analysis by electron microscopy, circular
      dichroism, and chemical denaturation, we found that AD seeded recombinant tau
      fibrils were not significantly different than tau fibrils isolated from AD brain
      tissue. Tau fibrils produced by incubating recombinant tau with heparin had
      significantly narrower fibrils with a longer periodicity, higher chemical
      stability, and distinct secondary structure compared to AD PHFs. The addition of
      heparin to the reaction of recombinant tau and AD PHFs also corrupted the
      templating process, resulting in a mixture of fibril conformations. Our results
      suggest that AD-isolated PHFs act as a conformational template for the formation
      of recombinant tau fibrils. Therefore, the use of AD PHFs as seeds to stimulate
      recombinant tau amyloid formation produces synthetic tau fibers that closely
      resemble those associated with AD pathology and provides a biochemical model of
      tau misfolding that may be of improved utility for structural studies and drug
      screening. These results also demonstrate that post-translational modifications
      such as phosphorylation are not a prerequisite for the propagation of the tau
      fibril conformation found in AD. 

PMID- 24033136
TI  - Trophic cascades from wolves to grizzly bears in Yellowstone.
AB  - We explored multiple linkages among grey wolves (Canis lupus), elk (Cervus
      elaphus), berry-producing shrubs and grizzly bears (Ursus arctos) in Yellowstone
      National Park. We hypothesized competition between elk and grizzly bears whereby,
      in the absence of wolves, increases in elk numbers would increase browsing on
      berry-producing shrubs and decrease fruit availability to grizzly bears. After
      wolves were reintroduced and with a reduced elk population, we hypothesized there
      would be an increase in the establishment of berry-producing shrubs, such as
      serviceberry (Amelanchier alnifolia), which is a major berry-producing plant. We
      also hypothesized that the percentage fruit in the grizzly bear diet would be
      greater after than before wolf reintroduction. We compared the frequency of fruit
      in grizzly bear scats to elk densities prior to wolf reintroduction during a time
      of increasing elk densities (1968-1987). For a period after wolf reintroduction,
      we calculated the percentage fruit in grizzly bear scat by month based on scats
      collected in 2007-2009 (n = 778 scats) and compared these results to scat data
      collected before wolf reintroduction. Additionally, we developed an age structure
      for serviceberry showing the origination year of stems in a northern range study
      area. We found that over a 19-year period, the percentage frequency of fruit in
      the grizzly diet (6231 scats) was inversely correlated (P < 0.001) with elk
      population size. The average percentage fruit in grizzly bear scats was higher
      after wolf reintroduction in July (0.3% vs. 5.9%) and August (7.8% vs. 14.6%)
      than before. All measured serviceberry stems accessible to ungulates originated
      since wolf reintroduction, while protected serviceberry growing in a nearby
      ungulate exclosure originated both before and after wolf reintroduction.
      Moreover, in recent years, browsing of serviceberry outside of the exclosure
      decreased while their heights increased. Overall, these results are consistent
      with a trophic cascade involving increased predation by wolves and other large
      carnivores on elk, a reduced and redistributed elk population, decreased
      herbivory and increased production of plant-based foods that may aid threatened
      grizzly bears.

PMID- 24033138
TI  - Toward ovine iPSCs.
AB  - Abstract Interest in pluripotent livestock stem cells has been with us for over 2
      decades, and although much has been claimed over the years, it is only recently
      that real progress has been achieved. The recent developments have revolved
      around the ability to reprogram somatic cells to become induced pluripotent stem
      cells (iPSCs). Progress has been achieved in porcine, bovine, equine, and ovine
      species; but for each species, the extent of progress is different. I review the
      position of ovine iPSCs and comment on the two main drivers for this work-to
      produce "better" cells for nuclear transfer and to develop a good in vitro system
      to study the early development of ruminants.

PMID- 24033137
TI  - Regulation of MSK1-Mediated NF-kappaB Activation Upon UVB Irradiation.
AB  - Nuclear Factor Kappa-B (NF-kappaB) is a transcription factor that controls
      expression of genes involved in the immune and inflammatory responses as well as
      being a key component in the onset of cancers. In this study, we provided
      evidence that mitogen- and stress-activated protein kinase (MSK1) is responsible
      for a noncanonical late-phase activation of NF-kappaB upon UVB irradiation. Our
      data demonstrated that following UVB irradiation, MSK1 is activated via
      phosphorylation at the 24 h time point coinciding with translocation of NF-kappaB
      into the nucleus. Investigations into the signaling pathways upstream of MSK1
      through the use of specific inhibitors for mitogen-activated protein kinase and
      p38 revealed that both kinases are required for full phosphorylation during the
      late phase (24 h), while p38 is paramount for phosphorylation during the early
      phase (6 h). Electromobility shift assays (EMSA) showed that inhibition of MSK1
      resulted in a marked reduction in NF-kappaB binding affinity without altering the
      nuclear translocation of NF-kappaB. Supershift EMSA implicate that the p65, but
      not p50, isoform of NF-kappaB is involved in late-phase activation in response to
      UVB irradiation. Together, the results of these studies shed light onto a novel
      pathway of MSK1-mediated late-phase activation of NF-kappaB in response to UVB
      irradiation.

PMID- 24033139
TI  - Some reminiscences of Keith Campbell.

PMID- 24033140
TI  - Sheep: the first large animal model in nuclear transfer research.
AB  - The scope of this article is not to provide an exhaustive review of nuclear
      transfer research, because many authoritative reviews exist on the biological
      issues related to somatic and embryonic cell nuclear transfer. We shall instead
      provide an overview on the work done specifically on sheep and the value of this
      work on the greater nuclear transfer landscape.

PMID- 24033143
TI  - Oil spill source identification by principal component analysis of electrospray
      ionization Fourier transform ion cyclotron resonance mass spectra.
AB  - One fundamental challenge with either acute or chronic oil spills is to identify
      the source, especially in highly polluted areas, near natural oil seeps, when the
      source contains more than one petroleum product or when extensive weathering has
      occurred. Here we focus on heavy fuel oil that spilled (~200,000 L) from two
      suspected fuel tanks that were ruptured on the motor vessel (M/V) Cosco Busan
      when it struck the San Francisco-Oakland Bay Bridge in November 2007. We
      highlight the utility of principal component analysis (PCA) of elemental
      composition data obtained by high resolution FT-ICR mass spectrometry to
      correctly identify the source of environmental contamination caused by the
      unintended release of heavy fuel oil (HFO). Using ultrahigh resolution
      electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass
      spectrometry, we uniquely assigned thousands of elemental compositions of
      heteroatom-containing species in neat samples from both tanks and then applied
      principal component analysis. The components were based on double bond
      equivalents for constituents of elemental composition, CcHhN1S1. To determine if
      the fidelity of our source identification was affected by weathering, field
      samples were collected at various intervals up to two years after the spill. We
      are able to identify a suite of polar petroleum markers that are environmentally
      persistent, enabling us to confidently identify that only one tank was the source
      of the spilled oil: in fact, a single principal component could account for 98%
      of the variance. Although identification is unaffected by the presence of higher
      polarity, petrogenic oxidation (weathering) products, future studies may require
      removal of such species by anion exchange chromatography prior to mass spectral
      analysis due to their preferential ionization by ESI.

PMID- 24033141
TI  - Interspecies somatic cell nuclear transfer: advancements and problems.
AB  - Embryologists working with livestock species were the pioneers in the field of
      reprogramming by somatic cell nuclear transfer (SCNT). Without the "Dolly
      experiment," the field of cellular reprogramming would have been slow and induced
      plutipotent cells (iPSCs) would not have been conceived. The major drive of the
      work in mammalian cloning was the interest of the breeding industry to propagate
      superior genotypes. Soon it was realized that the properties of oocytes could be
      used also to clone endangered mammalian species or to reprogram the genomes of
      unrelated species through what is known as interspecies (i) SCNT, using easily
      available oocytes of livestock species. iSCNT for cloning animals works only for
      species that can interbreed, and experiments with taxonomically distant species
      have not been successful in obtaining live births or deriving embryonic stem cell
      (ESC) lines to be used for regenerative medicine. There are controversial reports
      in the literature, but in most cases these experiments have underlined some of
      the cellular and molecular mechanisms that are incomplete during cell nucleus
      reprogramming, including the failure to organize nucleoli, silence somatic cell
      genes, activate the embryonic genome, and resume mitochondrial replication and
      function, thus indicating nucleus-cytoplasmic incompatibility.

PMID- 24033144
TI  - Proficiency testing for blood group genotyping.

PMID- 24033142
TI  - Bone marrow mesenchymal stem cells are an attractive donor cell type for
      production of cloned pigs as well as genetically modified cloned pigs by somatic
      cell nuclear transfer.
AB  - The somatic cell nuclear transfer (SCNT) technique has been widely applied to
      clone pigs or to produce genetically modified pigs. Currently, this technique
      relies mainly on using terminally differentiated fibroblasts as donor cells. To
      improve cloning efficiency, only partially differentiated multipotent mesenchymal
      stem cells (MSCs), thought to be more easily reprogrammed to a pluripotent state,
      have been used as nuclear donors in pig SCNT. Although in vitro-cultured embryos
      cloned from porcine MSCs (MSCs-embryos) were shown to have higher preimplantation
      developmental ability than cloned embryos reconstructed from fibroblasts (Fs
      embryos), the difference in in vivo full-term developmental rate between porcine
      MSCs-embryos and Fs-embryos has not been investigated so far. In this study, we
      demonstrated that blastocyst total cell number and full-term survival abilities
      of MSCs-embryos were significantly higher than those of Fs-embryos cloned from
      the same donor pig. The enhanced developmental potential of MSCs-embryos may be
      associated with their nuclear donors' DNA methylation profile, because we found
      that the methylation level of imprinting genes and repeat sequences differed
      between MSCs and fibroblasts. In addition, we showed that use of transgenic
      porcine MSCs generated from transgene plasmid transfection as donor cells for
      SCNT can produce live transgenic cloned pigs. These results strongly suggest that
      porcine bone marrow MSCs are a desirable donor cell type for production of cloned
      pigs and genetically modified cloned pigs via SCNT.

PMID- 24033145
TI  - Exploration of antimicrobial potential of essential oils of Cinnamomum
      glanduliferum, Feronia elephantum, Bupleurum hamiltonii and Cyclospermum
      leptophyllum against foodborne pathogens.
AB  - CONTEXT: Cinnamomum glanduliferum (Wall.) Meissn. (Lauraceae), Feronia elephantum
      Correa (Rutaceae), Bupleurum hamiltonii Balak (Apiaceae) and Cyclospermum
      leptophyllum (Pers.) Sprague ex Britton & P. Wilson (Apiaceae) are common species
      found in Northwest Himalaya and are widely used as folk medicine. The study
      became more interesting because hitherto there are no reports on the
      antimicrobial screening of these species with specific chemical composition.
      OBJECTIVE: The antimicrobial potential of the essential oils of C. glanduliferum,
      F. elephantum, B. hamiltonii and C. leptophyllum against some commonly occurring
      foodborne pathogenic and spoilage bacteria was explored in this study. MATERIALS
      AND METHODS: Antimicrobial screening studies of essential oils were performed
      against some Gram-positive and Gram-negative bacterial strains using broth
      dilution methods. Each essential oil was prepared by serial double dilution
      method to get final concentrations ranging from 0.85--440.0 ug/ml in a 96
      microtiter plate. RESULTS: The in vitro studies revealed that C. glanduliferum
      oil was very active against Gram-negative bacteria, A. salmonicida (MIC 1.72
      ug/ml), E. coli (MIC 3.43 ug/ml), and P. aeruginosa (MIC 3.43 ug/ml) as compared
      to the standards gentamicin and kanamicin. Oil of C. leptophyllum exhibited
      better inhibitory activity profile against Gram-positive S. aureus (MIC 3.43
      MUg/ml) and Gram-negative E. herbicola (MIC 1.72 MUg/ml) and P. aeruginosa (MIC
      3.43 MUg/ml) as compared to the standards. DISCUSSION AND CONCLUSION: These
      results reveal that these essential oils may be used in the treatment of diseases
      caused by the foodborne pathogenic and spoilage bacteria. Their importance as
      potential medicinal agents is based on the antimicrobial findings.

PMID- 24033146
TI  - Tests of an adaptive QM/MM calculation on free energy profiles of chemical
      reactions in solution.
AB  - We present reaction free energy calculations using the adaptive buffered force
      mixing quantum mechanics/molecular mechanics (bf-QM/MM) method. The bf-QM/MM
      method combines nonadaptive electrostatic embedding QM/MM calculations with
      extended and reduced QM regions to calculate accurate forces on all atoms, which
      can be used in free energy calculation methods that require only the forces and
      not the energy. We calculate the free energy profiles of two reactions in aqueous
      solution: the nucleophilic substitution reaction of methyl chloride with a
      chloride anion and the deprotonation reaction of the tyrosine side chain. We
      validate the bf-QM/MM method against a full QM simulation, and show that it
      correctly reproduces both geometrical properties and free energy profiles of the
      QM model, while the electrostatic embedding QM/MM method using a static QM region
      comprising only the solute is unable to do so. The bf-QM/MM method is not
      explicitly dependent on the details of the QM and MM methods, so long as it is
      possible to compute QM forces in a small region and MM forces in the rest of the
      system, as in a conventional QM/MM calculation. It is simple, with only a few
      parameters needed to control the QM calculation sizes, and allows (but does not
      require) a varying and adapting QM region which is necessary for simulating
      solutions.

PMID- 24033147
TI  - High nasal carriage of methicillin-resistant Staphylococcus aureus among healthy
      Tanzanian under-5 children.
AB  - This study aimed to determine the prevalence of Staphylococcus aureus and
      methicillin-resistant S. aureus (MRSA) carriage, risk factors of colonization and
      antimicrobial susceptibility patterns of S. aureus strains. The study was
      conducted at the Muhimbili National Hospital in Dar es Salaam, Tanzania. Nasal
      swabs were obtained from children and S. aureus was isolated and identified using
      conventional culture methods. MRSA was screened and confirmed using the cefoxitin
      disk and multiplex real-time polymerase chain reaction, respectively. Antibiotic
      susceptibility was performed using the Kirby-Bauer disk diffusion method. MRSA
      isolates were further characterized by pulsed field gel electrophoresis (PFGE)
      profiling. Of 285 children included in the study, S. aureus was detected in 114
      (40%). Of the 114 isolates, 12 (10.5%) were MRSA. PFGE results showed that these
      MRSA isolates are epidemiologically unrelated. Resistance of all S. aureus to
      trimethoprim-sulfamethoxazole, tetracycline, gentamicin, and ciprofloxacin was
      65.8%, 23.7%, 27.2%, and 4.4%, respectively. No resistance to vancomycin was
      found. The prevalence of inducible clindamycin resistance, constitutive
      clindamycin resistance, MS phenotype (resistance to erythromycin alone), and
      multidrug resistance was 16.7%, 1.8%, 14.0%, and 16.8%, respectively. None of the
      risk factors examined was found to be significant. This is the first report of S.
      aureus and nasal carriage of MRSA and a high rate of S. aureus carriage was found
      in Tanzanian under-5 children. The study findings support the need for proper
      health education and effective infection control measures for healthcare workers.

PMID- 24033148
TI  - Advancing allele group-specific amplification of the complete HLA-C gene-
      isolation of novel alleles from three allele groups (C*04, C*07 and C*08).
AB  - A variety of strategies have been designed for sequence-based HLA typing (SBT)
      and for the isolation of new human leucocyte antigen (HLA) alleles, but
      unambiguous characterization of complete genomic sequences remains a challenge.
      We recently reported a simple method for the group-specific amplification (GSA)
      and sequencing of a full-length C*04 genomic sequence in isolation from the
      accompanying allele. Here we build on this strategy and present homologous
      methods that enable the isolation of HLA-C alleles belonging to another two
      allele groups. Using this approach, which can be applied to sequence-based typing
      in some clinical settings, we have successfully characterized three novel HLA-C
      alleles (C*04:128, C*07:01:01:02, and C*08:62). 

PMID- 24033149
TI  - Mutations of the GATA2 and CEBPA genes in paediatric acute myeloid leukaemia.

PMID- 24033150
TI  - Secondary metabolites from the Chinese liverwort Cephaloziella kiaeri.
AB  - Sixteen new clerodane diterpenoids, cephaloziellins A-P (1-16), and two known
      analogues (17 and 18) were isolated from an EtOH extract of the Chinese liverwort
      Cephaloziella kiaeri. The structures of the new compounds were elucidated from
      extensive spectroscopic data (IR, UV, HRESIMS, 1D NMR, and 2D NMR), and the
      structures of 5, 9, and 15 were confirmed by single-crystal X-ray diffraction
      analyses. The absolute configurations of all new compounds were established by
      comparing experimental and calculated electronic circular dichroism spectra. 

PMID- 24033151
TI  - Degradation of polar organic micropollutants during riverbank filtration:
      complementary results from spatiotemporal sampling and push-pull tests.
AB  - The fate of polar organic micropollutants (logDOW (pH 7) between -4.2 and +3.5)
      during riverbank filtration (RBF) at the river Thur was studied using both
      spatiotemporally resolved sampling and single-well push-pull tests (PPT),
      followed by LC-MS/MS analysis. The Thur is a dynamic prealpine river with an
      alluvial sandy-gravel aquifer, which is characterized by short groundwater travel
      times (a few days) from surface water infiltration to groundwater extraction. The
      spatiotemporal sampling allowed tracing concentration dynamics in the river and
      the groundwater and revealed persistence for the drug carbamazepine, while the
      herbicide MCPA (2-methyl-4-chloro-phenoxyacetic acid) and the drug 4
      acetamidoantipyrine were very quickly degraded under the prevalent aerobic
      conditions. The corrosion inhibitor 1H-benzotriazole was degraded slightly,
      particularly in a transect influenced by river restoration measures. For the
      first time in situ first-order degradation rate constants for three pesticides
      and two pharmaceuticals were determined by PPTs, which confirmed the results of
      the spatiotemporal sampling. Atenolol was transformed almost completely to
      atenolol acid. Rate constants of 0.1-1.3 h(-1) for MCPA, 2,4-D, mecoprop,
      atenolol, and diclofenac, corresponding to half-lives of 0.6-6.3 h, demonstrated
      the great potential of RBF systems to degrade organic micropollutants and
      simultaneously the applicability of PPTs for micropollutants in such dynamic
      systems. 

PMID- 24033152
TI  - Event centrality and posttraumatic outcomes in the context of pervasive violence:
      a study of teachers in El Salvador.
AB  - It is well established that the importance assigned to a trauma can affect one's
      recovery and psychological health in numerous ways. Event centrality is an
      increasingly popular construct that captures the tendency among survivors to
      reevaluate and possibly accommodate their worldviews posttrauma. The centrality
      given to trauma appears to serve as a "double-edged sword" in that this construct
      might factor prominently in both posttraumatic stress disorder (PTSD) and
      posttraumatic growth (PTG). Focusing on 257 violence-exposed teachers from
      educational departments throughout El Salvador, we examined whether the
      centrality assigned by the teachers to stressful life events uniquely predicted
      both PTSD symptomatology and PTG. Results revealed that event centrality was
      positively related to both PTSD and PTG, even when controlling for demographic
      factors, violence exposure, and depression. In addition, PTSD symptomatology and
      PTG were not associated with one another in this sample. In summary, these
      findings support the role of event centrality as a contributing factor for PTSD
      and PTG among persons exposed to pervasive trauma. 

PMID- 24033154
TI  - The acute inflammatory response to photodynamic therapy.

PMID- 24033155
TI  - Commentary: daily care of aged skin.

PMID- 24033156
TI  - Bath vs. oral psoralen plus ultraviolet A: is one more effective than the other?

PMID- 24033157
TI  - Neurotensin serum levels and skin gene expression are increased in atopic
      dermatitis.
AB  - BACKGROUND: Neurotensin (NT) participates in immune responses, but the mechanisms
      are not known. We have previously shown that NT augments the ability of
      corticotropin-releasing hormone (CRH) to increase mast-cell-dependent vascular
      permeability in rodents. We also showed that NT stimulates human mastcell release
      of vascular endothelial growth factor, and that CRH is increased in the serum of
      patients with atopic dermatitis (AD), an inflammatory skin condition involving
      mast cells. OBJECTIVES: To measure serum levels of NT, and lesional skin
      expression of NT and the main NT receptor (NTR-1) in AD, and to compare it with
      skin expression in chronic urticaria (CU) and urticaria pigmentosa (UP). METHODS:
      Serum NT was measured with a Milliplex microbead array. Skin NT and NTR-1 gene
      expression was determined with quantitative polymerase chain reaction.
      Immunohistochemistry was performed using a mouse monoclonal antibody for NT, and
      a rabbit polyclonal antibody for NTR-1. Mast cells were counterstained with Leder
      dye. RESULTS: Neurotensin is significantly elevated in the serum of patients with
      AD compared with healthy controls (P = 0.0001). NT gene expression is also
      significantly increased in lesional skin of patients with AD compared with
      controls (P = 0.0194). Moreover, immunohistochemistry of AD lesions shows NT >
      NTR-1 staining of perivascular cells, many of which are identified as mast cells
      after staining with Leder dye. There was no statistically significant difference
      in NT and NTR-1 lesional skin gene expression in patients with either CU or UP.
      CONCLUSIONS: These results suggest that interactions between NT and mast cells
      may occur and contribute to AD pathogenesis.

PMID- 24033159
TI  - Comment on: Rural Generalism and the Queensland Health pathway--implications for
      rural clinical supervisors, placements and rural medical education providers.

PMID- 24033160
TI  - Genome evolution and speciation: toward quantitative descriptions of pattern and
      process.
AB  - Studies of patterns of differentiation across genomes are accumulating, yet
      integrative work that combines approaches and fully capitalizes on new
      technologies to test explicit hypotheses is still rare. Thus, debates persist
      about the rate, magnitude, and causes of genomic change. This special section is
      devoted to helping resolve these debates. The eight studies contained within
      demonstrate how we can begin to move away from vague metaphors toward
      quantitative and more precise descriptors of patterns of genetic architecture and
      divergence. However, a particular genomic pattern can often arise via different
      combinations of various processes such as selection, gene flow, recombination,
      mutation, genetic drift, and demographic variability. Thus, substantial
      challenges remain in elucidating which evolutionary processes generated observed
      genomic patterns. Nonetheless, the studies in this section demonstrate ways
      forward toward bridging pattern and process, including experimental work, genetic
      mapping, increased knowledge of natural history and demography, and comparative
      studies spanning taxa at different points in the speciation continuum. Such
      collective work will lead to more powerful hypothesis testing. Future work can
      also help better integrate the contributions of ecology, genome structure (e.g.,
      inversions and translocations), and genetic conflict to genome evolution. 

PMID- 24033161
TI  - Divergence is focused on few genomic regions early in speciation: incipient
      speciation of sunflower ecotypes.
AB  - Early in speciation, as populations undergo the transition from local adaptation
      to incipient species, is when a number of transient, but potentially important,
      processes appear to be most easily detected. These include signatures of
      selective sweeps that can point to asymmetry in selection between habitats,
      divergence hitchhiking, and associations of adaptive genes with environments. In
      a genomic comparison of ecotypes of the prairie sunflower, Helianthus petiolaris,
      occurring at Great Sand Dunes National Park and Preserve (Colorado), we found
      that selective sweeps were mainly restricted to the dune ecotype and that there
      was variation across the genome in whether proximity to the nondune population
      constrained or promoted divergence. The major regions of divergence were few and
      large between ecotypes, in contrast with an interspecific comparison between H.
      petiolaris and a sympatric congener, Helianthus annuus. In general, the large
      regions of divergence observed in the ecotypic comparison swamped locus-specific
      associations with environmental variables. In both comparisons, regions of high
      divergence occurred in portions of the genetic map with high marker density,
      probably reflecting regions of low recombination. The difference in genomic
      distributions of highly divergent regions between ecotypic and interspecific
      comparisons highlights the value of studies spanning the spectrum of speciation
      in related taxa. 

PMID- 24033162
TI  - The genetic architecture of reproductive isolation during speciation-with-gene
      flow in lake whitefish species pairs assessed by RAD sequencing.
AB  - During speciation-with-gene-flow, effective migration varies across the genome as
      a function of several factors, including proximity of selected loci,
      recombination rate, strength of selection, and number of selected loci. Genome
      scans may provide better empirical understanding of the genome-wide patterns of
      genetic differentiation, especially if the variance due to the previously
      mentioned factors is partitioned. In North American lake whitefish (Coregonus
      clupeaformis), glacial lineages that diverged in allopatry about 60,000 years ago
      and came into contact 12,000 years ago have independently evolved in several
      lakes into two sympatric species pairs (a normal benthic and a dwarf limnetic).
      Variable degrees of reproductive isolation between species pairs across lakes
      offer a continuum of genetic and phenotypic divergence associated with adaptation
      to distinct ecological niches. To disentangle the complex array of genetically
      based barriers that locally reduce the effective migration rate between whitefish
      species pairs, we compared genome-wide patterns of divergence across five lakes
      distributed along this divergence continuum. Using restriction site associated
      DNA (RAD) sequencing, we combined genetic mapping and population genetics
      approaches to identify genomic regions resistant to introgression and derive
      empirical measures of the barrier strength as a function of recombination
      distance. We found that the size of the genomic islands of differentiation was
      influenced by the joint effects of linkage disequilibrium maintained by selection
      on many loci, the strength of ecological niche divergence, as well as demographic
      characteristics unique to each lake. Partial parallelism in divergent genomic
      regions likely reflected the combined effects of polygenic adaptation from
      standing variation and independent changes in the genetic architecture of
      postzygotic isolation. This study illustrates how integrating genetic mapping and
      population genomics of multiple sympatric species pairs provide a window on the
      speciation-with-gene-flow mechanism. 

PMID- 24033163
TI  - Genome divergence and the genetic architecture of barriers to gene flow between
      Lycaeides idas and L. Melissa.
AB  - Genome divergence during speciation is a dynamic process that is affected by
      various factors, including the genetic architecture of barriers to gene flow.
      Herein we quantitatively describe aspects of the genetic architecture of two sets
      of traits, male genitalic morphology and oviposition preference, that putatively
      function as barriers to gene flow between the butterfly species Lycaeides idas
      and L. melissa. Our analyses are based on unmapped DNA sequence data and a
      recently developed Bayesian regression approach that includes variable selection
      and explicit parameters for the genetic architecture of traits. A modest number
      of nucleotide polymorphisms explained a small to large proportion of the
      variation in each trait, and average genetic variant effects were nonnegligible.
      Several genetic regions were associated with variation in multiple traits or with
      trait variation within- and among-populations. In some instances, genetic regions
      associated with trait variation also exhibited exceptional genetic
      differentiation between species or exceptional introgression in hybrids. These
      results are consistent with the hypothesis that divergent selection on male
      genitalia has contributed to heterogeneous genetic differentiation, and that both
      sets of traits affect fitness in hybrids. Although these results are encouraging,
      we highlight several difficulties related to understanding the genetics of
      speciation. 

PMID- 24033164
TI  - Convergence and divergence during the adaptation to similar environments by an
      Australian groundsel.
AB  - Adaptation to replicate environments is often achieved through similar phenotypic
      solutions. Whether selection also produces convergent genomic changes in these
      situations remains largely unknown. The variable groundsel, Senecio lautus, is an
      excellent system to investigate the genetic underpinnings of convergent
      evolution, because morphologically similar forms of these plants have adapted to
      the same environments along the coast of Australia. We compared range-wide
      patterns of genomic divergence in natural populations of this plant and searched
      for regions putatively affected by natural selection. Our results indicate that
      environmental adaptation followed complex genetic trajectories, affecting
      multiple loci, implying both the parallel recruitment of the same alleles and the
      divergence of completely different genomic regions across geography. An analysis
      of the biological functions of candidate genes suggests that adaptation to
      coastal environments may have occurred through the recruitment of different genes
      participating in similar processes. The relatively low genetic convergence that
      characterizes the parallel evolution of S. lautus forms suggests that evolution
      is more constrained at higher levels of biological organization. 

PMID- 24033165
TI  - Heterogeneous Genomic Differentiation in marine threespine sticklebacks:
      adaptation along an environmental gradient.
AB  - Evolutionary divergence among populations occupying ecologically distinct
      environments can occur even in the face of on-going gene flow. However, the
      genetic underpinnings, as well as the scale and magnitude at which this
      differentiation occurs in marine habitats are not well understood. We
      investigated the patterns and degree of genomic heterogeneity in threespine
      sticklebacks (Gasterosteus aculeatus) by assessing genetic variability in 20
      nongenic and 20 genic (associated with genes important for freshwater adaptation)
      microsatellite loci in samples collected from 38 locations spanning the entire
      Baltic Sea coast to the North Sea boundary. Population divergence (F(ST) ~ 0.026)
      and structuring (five genetic clusters) was significantly more pronounced in the
      genic as compared to nongenic markers (F(ST) ~ 0.008; no genetic clusters).
      Patterns of divergence in the genic markers--45% of which were identified as
      outliers--correlated with local differences in salinity. Yet, a strong positive
      correlation between divergence in genic and nongenic markers, and their
      association with environmental factors suggests that adaptive divergence is
      reducing gene flow across the genome. Apart from providing a clear demonstration
      of heterogeneous genomic patterns of differentiation in a marine species, the
      results are indicative of adaptive population structuring across the relatively
      young Baltic Sea in spite of ample opportunities for gene flow.

PMID- 24033166
TI  - Chromosomal rearrangements and the genetics of reproductive barriers in mimulus
      (monkey flowers).
AB  - Chromosomal rearrangements may directly cause hybrid sterility and can facilitate
      speciation by preserving local adaptation in the face of gene flow. We used
      comparative linkage mapping with shared gene-based markers to identify potential
      chromosomal rearrangements between the sister monkeyflowers Mimulus lewisii and
      Mimulus cardinalis, which are textbook examples of ecological speciation. We then
      remapped quantitative trait loci (QTLs) for floral traits and flowering time
      (premating isolation) and hybrid sterility (postzygotic isolation). We identified
      three major regions of recombination suppression in the M. lewisii * M.
      cardinalis hybrid map compared to a relatively collinear Mimulus parishii * M.
      lewisii map, consistent with a reciprocal translocation and two inversions
      specific to M. cardinalis. These inferences were supported by targeted
      intraspecific mapping, which also implied a M. lewisii-specific reciprocal
      translocation causing chromosomal pseudo-linkage in both hybrid mapping
      populations. Floral QTLs mapped in this study, along with previously mapped
      adaptive QTLs, were clustered in putatively rearranged regions. All QTLs for male
      sterility, including two underdominant loci, mapped to regions of recombination
      suppression. We argue that chromosomal rearrangements may have played an
      important role in generating and consolidating barriers to gene flow as natural
      selection drove the dramatic ecological and morphological divergence of these
      species. 

PMID- 24033167
TI  - Genetic divergence along the speciation continuum: the transition from host race
      to species in rhagoletis (Diptera: tephritidae).
AB  - Studies of related populations varying in their degrees of reproductive isolation
      can provide insights into speciation. Here, the transition from partially
      isolated host races to more fully separated sibling species is investigated by
      comparing patterns of genetic differentiation between recently evolved (~150
      generations) apple and ancestral hawthorn-infesting populations of Rhagoletis
      pomonella to their sister taxon, the undescribed flowering dogwood fly attacking
      Cornus florida. No fixed or diagnostic private alleles differentiating the three
      populations were found at any of 23 microsatellites and 10 allozymes scored.
      Nevertheless, allele frequency differences were sufficient across loci for
      flowering dogwood fly populations from multiple localities to form a diagnosable
      genotypic cluster distinct from apple and hawthorn flies, indicative of species
      status. Genome-wide patterns of differentiation were correlated between the host
      races and species pair comparisons along the majority of chromosomes, suggesting
      that similar disruptive selection pressures affect most loci. However,
      differentiation was more pronounced, with some additional regions showing
      elevated divergence, for the species pair comparison. Our results imply that
      Rhagoletis sibling species such as the flowering dogwood fly represent host races
      writ large, with the transition to species status primarily resulting from
      increased divergence of the same regions separating apple and hawthorn flies. 

PMID- 24033168
TI  - Genetic hitchhiking and the dynamic buildup of genomic divergence during
      speciation with gene flow.
AB  - A major issue in evolutionary biology is explaining patterns of differentiation
      observed in population genomic data, as divergence can be due to both direct
      selection on a locus and genetic hitchhiking. "Divergence hitchhiking" (DH)
      theory postulates that divergent selection on a locus reduces gene flow at
      physically linked sites, facilitating the formation of localized clusters of
      tightly linked, diverged loci. "Genome hitchhiking" (GH) theory emphasizes genome
      wide effects of divergent selection. Past theoretical investigations of DH and GH
      focused on static snapshots of divergence. Here, we used simulations assessing a
      variety of strengths of selection, migration rates, population sizes, and
      mutation rates to investigate the relative importance of direct selection, GH,
      and DH in facilitating the dynamic buildup of genomic divergence as speciation
      proceeds through time. When divergently selected mutations were limiting, GH
      promoted divergence, but DH had little measurable effect. When populations were
      small and divergently selected mutations were common, DH enhanced the
      accumulation of weakly selected mutations, but this contributed little to
      reproductive isolation. In general, GH promoted reproductive isolation by
      reducing effective migration rates below that due to direct selection alone, and
      was important for genome-wide "congealing" or "coupling" of differentiation
      (F(ST)) across loci as speciation progressed.

PMID- 24033169
TI  - On the findability of genotypes.
AB  - Can we define a measure that describes how easy or difficult it is for a
      population to evolve to a specific genotype? For populations evolving under weak
      mutation on a time-invariant fitness landscape, I argue that one appropriate
      measure is the expected waiting time, starting from equilibrium, for a population
      to become fixed for a given genotype. Under this definition for the "findability"
      of genotypes, I show that for any pair of genotypes (1) a population at
      equilibrium is always more likely to fix at the more findable before the less
      findable genotype and (2) the expected time to evolve from the more findable to
      the less findable genotype is always greater that the expected time to evolve in
      the opposite direction. Although increasing the fitness of a genotype always
      increases its findability, in general there is no simple relationship between the
      rank ordering of genotypes by fitness and the rank ordering of genotypes by
      findability. I also present a method for quantifying the relative contributions
      of mutation, selection, substitution rate, and probability of reversion to a
      genotype's findability. 

PMID- 24033170
TI  - Short indels are subject to insertion-biased gene conversion.
AB  - Recombination between homologous loci is accompanied by formation of
      heteroduplexes. Repairing mismatches in heteroduplexes often leads to single
      nucleotide substitutions in a process known as gene conversion. Gene conversion
      was shown to be GC-biased in different organisms; that is, a W(A or T)->S(G or C)
      substitution is more likely in this process than a S->W substitution. Here, we
      show that the insertion/deletion ratio for short noncoding indels that reach
      fixation between species is positively correlated with the recombination rate in
      Drosophila melanogaster, Homo sapiens, and Saccharomyces cerevisiae. This
      correlation is both due to an increase of the fixation rate of insertions and
      decrease of the fixation rate of deletions in regions of high recombination.
      Whole-genome data on indel polymorphism and divergence in D. melanogaster rule
      out mutation biases and selection as the cause of this trend, pointing to
      insertion-biased gene conversion as the most likely explanation. The bias toward
      insertions is the strongest for single-nucleotide indels, and decreases with
      indel length. In regions of high recombination rate this bias leads to an up to
      ~5-fold excess of fixed short insertions over deletions, and substantially
      affects the evolution of DNA segments. 

PMID- 24033171
TI  - Evolution of viviparity: a phylogenetic test of the cold-climate hypothesis in
      phrynosomatid lizards.
AB  - The evolution of viviparity is a key life-history transition in vertebrates, but
      the selective forces favoring its evolution are not fully understood. With >100
      origins of viviparity, squamate reptiles (lizards and snakes) are ideal for
      addressing this issue. Some evidence from field and laboratory studies supports
      the "cold-climate" hypothesis, wherein viviparity provides an advantage in cold
      environments by allowing mothers to maintain higher temperatures for developing
      embryos. Surprisingly, the cold-climate hypothesis has not been tested using both
      climatic data and phylogenetic comparative methods. Here, we investigate the
      evolution of viviparity in the lizard family Phrynosomatidae using GIS-based
      environmental data, an extensive phylogeny (117 species), and recently developed
      comparative methods. We find significant relationships between viviparity and
      lower temperatures during the warmest (egg-laying) season, strongly supporting
      the cold-climate hypothesis. Remarkably, we also find that viviparity tends to
      evolve more frequently at tropical latitudes, despite its association with cooler
      climates. Our results help explain this and two related patterns that seemingly
      contradict the cold-climate hypothesis: the presence of viviparous species
      restricted to low-elevation tropical regions and the paucity of viviparous
      species at high latitudes. Finally, we examine whether viviparous taxa may be at
      higher risk of extinction from anthropogenic climate change. 

PMID- 24033172
TI  - An adaptive radiation of frogs in a southeast Asian island archipelago.
AB  - Living amphibians exhibit a diversity of ecologies, life histories, and species
      rich lineages that offers opportunities for studies of adaptive radiation. We
      characterize a diverse clade of frogs (Kaloula, Microhylidae) in the Philippine
      island archipelago as an example of an adaptive radiation into three primary
      habitat specialists or ecotypes. We use a novel phylogenetic estimate for this
      clade to evaluate the tempo of lineage accumulation and morphological
      diversification. Because species-level phylogenetic estimates for Philippine
      Kaloula are lacking, we employ dense population sampling to determine the
      appropriate evolutionary lineages for diversification analyses. We explicitly
      take phylogenetic uncertainty into account when calculating diversification and
      disparification statistics and fitting models of diversification. Following
      dispersal to the Philippines from Southeast Asia, Kaloula radiated rapidly into
      several well-supported clades. Morphological variation within Kaloula is partly
      explained by ecotype and accumulated at high levels during this radiation,
      including within ecotypes. We pinpoint an axis of morphospace related directly to
      climbing and digging behaviors and find patterns of phenotypic evolution
      suggestive of ecological opportunity with partitioning into distinct habitat
      specialists. We conclude by discussing the components of phenotypic diversity
      that are likely important in amphibian adaptive radiations. 

PMID- 24033173
TI  - Genetic differentiation and selection against migrants in evolutionarily
      replicated extreme environments.
AB  - We investigated mechanisms of reproductive isolation in livebearing fishes (genus
      Poecilia) inhabiting sulfidic and nonsulfidic habitats in three replicate river
      drainages. Although sulfide spring fish convergently evolved divergent
      phenotypes, it was unclear if mechanisms of reproductive isolation also evolved
      convergently. Using microsatellites, we found strongly reduced gene flow between
      adjacent populations from different habitat types, suggesting that local
      adaptation to sulfidic habitats repeatedly caused the emergence of reproductive
      isolation. Reciprocal translocation experiments indicate strong selection against
      immigrants into sulfidic waters, but also variation among drainages in the
      strength of selection against immigrants into nonsulfidic waters. Mate choice
      experiments revealed the evolution of assortative mating preferences in females
      from nonsulfidic but not from sulfidic habitats. The inferred strength of sexual
      selection against immigrants (RI(s)) was negatively correlated with the strength
      of natural selection (RI(m)), a pattern that could be attributed to
      reinforcement, whereby natural selection strengthens behavioral isolation due to
      reduced hybrid fitness. Overall, reproductive isolation and genetic
      differentiation appear to be replicated and direct consequences of local
      adaptation to sulfide spring environments, but the relative contributions of
      different mechanisms of reproductive isolation vary across these evolutionarily
      independent replicates, highlighting both convergent and nonconvergent
      evolutionary trajectories of populations in each drainage.

PMID- 24033175
TI  - How selfing, inbreeding depression, and pollen limitation impact nuclear
      cytoplasmic gynodioecy: a model.
AB  - Gynodioecy, the co-occurrence of females and hermaphrodites, is often due to
      conflicting interactions between cytoplasmic male sterility genes and nuclear
      restorers. Although gynodioecy often occurs in self-compatible species, the
      effect of self-pollination, inbreeding depression, and pollen limitation acting
      differently on females and hermaphrodites remains poorly known in the case of
      nuclear-cytoplasmic gynodioecy (NCG). In this study, we model NCG in an infinite
      population and we study the effect of selfing rate, inbreeding depression, and
      pollen limitation on the maintenance of gynodioecy and on sex ratios at
      equilibrium. We found that selfing and inbreeding depression have a strong
      impact, which depends on whether restorer cost acts on male or female fitness.
      When cost affects male fitness, the strength of cost has no effect, whereas
      selfing and inbreeding depression only impact gynodioecy by modifying the value
      of the female advantage. When cost affects female fitness, selfing facilitates
      NCG and reduces the role of strength of the cost, even when no inbreeding
      depression occurs, whereas inbreeding depression globally restricts the
      maintenance of the polymorphism. Finally, we found that pollen limitation could
      additionally strongly modify the dynamic of gynodioecy. We discuss our findings
      in the light of empirical data available in gynodioecious species. 

PMID- 24033174
TI  - Sexual traits are sensitive to genetic stress and predict extinction risk in the
      stalk-eyed fly, Diasemopsis meigenii.
AB  - The handicap principle predicts that sexual traits are more susceptible to
      inbreeding depression than nonsexual traits. However, this hypothesis has
      received little testing and results are inconsistent. We used 11 generations of
      full-sibling mating to test the effect of inbreeding on sexual and nonsexual
      traits in the stalk-eyed fly Diasemopsis meigenii. Consistent with the
      theoretical predictions, the male sexual trait (eyespan) decreased more than
      nonsexual traits (female eyespan and male wing length), even after controlling
      for body size variation. In addition, male eyespan was a reliable predictor of
      line extinction, unlike other nonsexual traits. After 11 generations, inbred
      lines were crossed to generate inbred and outbred families. All morphological
      traits were larger in outbred individuals than inbred individuals. This heterosis
      was greater in male eyespan than in male wing length, but not female eyespan. The
      elevated response in male eyespan to genetic stress mirrored the result found
      using environmental stress during larval development and suggests that common
      mechanisms underlie the patterns observed. Overall, these results support the
      hypothesis that male sexual traits suffer more from inbreeding depression than
      nonsexual traits and are in line with predictions based on the handicap
      principle. 

PMID- 24033176
TI  - Intraclutch differences in egg characteristics mitigate the consequences of age
      related hierarchies in a wild passerine.
AB  - The relative age of an individual's siblings is a major cause of fitness
      variation in many species. In Blue tits (Cyanistes caeruleus), we show that age
      hierarchies are predominantly caused by incubation preclutch completion, such
      that last laid eggs hatch later than early laid eggs. However, after
      statistically controlling for incubation behavior late laid eggs are shown to
      hatch more quickly than early laid eggs reducing the amount of asynchrony. By
      experimentally switching early and late laid eggs between nests on the day they
      were laid, we controlled for the effect of differential incubation and found that
      the faster hatching times of late laid eggs remains. Chicks that hatched earlier
      were heavier and had higher probability of fledgling, and chicks that hatched
      from experimental eggs had patterns of growth and survival consistent with this.
      Egg mass explained a small part of this variation, but the remainder must be due
      to egg composition. These results are consistent with the idea that intrinsic
      differences between eggs across the laying sequence serve to mitigate the effects
      of age-related hierarchies. We also show that between-clutch variation in
      prenatal developmental rate exists and that it is mainly environmental in origin
      rather than genetic. 

PMID- 24033177
TI  - Disentangling genetic and prenatal sources of familial resemblance across
      ontogeny in a wild passerine.
AB  - Cross-fostering experiments are widely used by quantitative geneticists to study
      genetics and by behavioral ecologists to study the effects of prenatal
      investment. Generally, the effects of genes and prenatal investment are
      confounded and the interpretation given to such experiments is largely dependent
      on the interests of the researcher. Using a large-scale well-controlled
      experiment on a wild population of blue tits (Cyanistes caeruleus), we are able
      to partition variation in body mass across ontogeny into the effects of genes and
      the effects of between-clutch variation in egg characteristics. We show that
      although egg effects are important early in ontogeny they quickly dissipate,
      suggesting that the genetic interpretation of cross-fostering experiments may be
      preferable for many types of trait. However, the heritability of body mass is
      smaller than has previously been reported. Our results suggest that this is due
      to a combination of controlling postnatal environmental effects more carefully
      and accounting for viability selection operating early in ontogeny. 

PMID- 24033178
TI  - Pupariation site preference within and between Drosophila sibling species.
AB  - Holometabolous insects pass through a sedentary pupal stage and often choose a
      location for pupation that is different from the site of larval feeding. We have
      characterized a difference in pupariation site choice within and between sibling
      species of Drosophila. We found that, in nature, Drosophila sechellia pupariate
      within their host fruit, Morinda citrifolia, and that they perform this behavior
      in laboratory assays. In contrast, in the laboratory, geographically diverse
      strains of Drosophila simulans vary in their pupariation site preference; D.
      simulans lines from the ancestral range in southeast Africa pupariate on fruit,
      or a fruit substitute, whereas populations from Europe or the New World select
      sites off of fruit. We explored the genetic basis for the evolved preference in
      puariation site preference by performing quantitative trait locus mapping within
      and between species. We found that the interspecific difference is controlled
      largely by loci on chromosomes X and II. In contrast, variation between two
      strains of D. simulans appears to be highly polygenic, with the majority of
      phenotypic effects due to loci on chromosome III. These data address the genetic
      basis of how new traits arise as species diverge and populations disperse. 

PMID- 24033179
TI  - Patterns of mating, generation of diversity, and fitness of offspring in a Geum
      hybrid swarm.
AB  - To understand the evolutionary consequences of hybridization between the
      outcrossing plant Geum rivale (Rosaceae) and the selfer Geum urbanum, we tested
      the predictions of two simple models that assume either (A) low or (B) high
      pollen fitness in hybrids. Model A predicts only four genotypic classes (G.
      rivale, G. rivale backcross [BC(R)], F1, and Geum urbanum) and asymmetric
      introgression from inbreeding to outbreeding species. Model B predicts additional
      genotypic classes and potential generation of novel inbreeding lines in the
      hybrid swarm. Amplified fragment length polymorphism (AFLP) analysis of adults
      revealed only the four genotypes predicted by model A. However, microsatellite
      analysis of parent-progeny arrays demonstrated production of selfed offspring by
      F1 and BC(R) maternal parents and contribution of these genotypes to outcross
      pollen pools, as predicted by model B. Moreover, AFLP and morphological analysis
      showed that the offspring generation comprised genotypes and phenotypes covering
      the entire spectrum of variation between the two parental species, in line with
      model B. A common garden experiment indicated no systematic reduction in fitness
      of offspring derived from hybrid parents. The genetic structure of the adults in
      the Geum hybrid swarm cannot be explained by restricted mating patterns but may
      result from ecological selection acting on a diverse offspring population.

PMID- 24033180
TI  - Body and limb size dissociation at the origin of birds: uncoupling allometric
      constraints across a macroevolutionary transition.
AB  - The origin of birds and powered flight is a classic major evolutionary
      transition. Research on their origin often focuses on the evolution of the wing
      with trends of forelimb elongation traced back through many nonavian maniraptoran
      dinosaurs. We present evidence that the relative forelimb elongation within avian
      antecedents is primarily due to allometry and is instead driven by a reduction in
      body size. Once body size is factored out, there is no trend of increasing
      forelimb length until the origin of birds. We report that early birds and
      nonavian theropods have significantly different scaling relationships within the
      forelimb and hindlimb skeleton. Ancestral forelimb and hindlimb allometric
      scaling to body size is rapidly decoupled at the origin of birds, when wings
      significantly elongate, by evolving a positive allometric relationship with body
      size from an ancestrally negative allometric pattern and legs significantly
      shorten by keeping a similar, near isometric relationship but with a reduced
      intercept. These results have implications for the evolution of powered flight
      and early diversification of birds. They suggest that their limb lengths first
      had to be dissociated from general body size scaling before expanding to the wide
      range of fore and hindlimb shapes and sizes present in today's birds. 

PMID- 24033181
TI  - Stepwise evolution of resistance to toxic cardenolides via genetic substitutions
      in the Na+/K+ -ATPase of milkweed butterflies (lepidoptera: Danaini).
AB  - Despite the monarch butterfly (Danaus plexippus) being famous for its adaptations
      to the defensive traits of its milkweed host plants, little is known about the
      macroevolution of these traits. Unlike most other animal species, monarchs are
      largely insensitive to cardenolides, because their target site, the sodium pump
      (Na(+)/K(+) -ATPase), has evolved amino acid substitutions that reduce
      cardenolide binding (so-called target site insensitivity, TSI). Because many, but
      not all, species of milkweed butterflies (Danaini) are associated with
      cardenolide-containing host plants, we analyzed 16 species, representing all
      phylogenetic lineages of milkweed butterflies, for the occurrence of TSI by
      sequence analyses of the Na(+)/K(+) -ATPase gene and by enzymatic assays with
      extracted Na(+)/K(+) -ATPase. Here we report that sensitivity to cardenolides was
      reduced in a stepwise manner during the macroevolution of milkweed butterflies.
      Strikingly, not all Danaini typically consuming cardenolides showed TSI, but
      rather TSI was more strongly associated with sequestration of toxic cardenolides.
      Thus, the interplay between bottom-up selection by plant compounds and top-down
      selection by natural enemies can explain the evolutionary sequence of adaptations
      to these toxins.

PMID- 24033182
TI  - Epistatic interactions determine the mutational pathways and coexistence of
      lineages in clonal Escherichia coli populations.
AB  - Understanding how diversity emerges in a single niche is not fully understood.
      Rugged fitness landscapes and epistasis between beneficial mutations could
      explain coexistence among emerging lineages. To provide an experimental test of
      this notion, we investigated epistasis among four pleiotropic mutations in rpoS,
      mglD, malT, and hfq present in two coexisting lineages that repeatedly fixed in
      experimental populations of Escherichia coli. The mutations were transferred into
      the ancestral background individually or in combination of double or triple
      alleles. The combined competitive fitness of two or three beneficial mutations
      from the same lineage was consistently lower than the sum of the competitive
      fitness of single mutants--a clear indication of negative epistasis within
      lineages. We also found sign epistasis (i.e., the combined fitness of two
      beneficial mutations lower than the ancestor), not only from two different
      lineages (i.e., hfq and rpoS) but also from the same lineage (i.e., mglD and
      malT). The sign epistasis between loci of different lineages indeed indicated a
      rugged fitness landscape, providing an epistatic explanation for the coexistence
      of distinct rpoS and hfq lineages in evolving populations. The negative and sign
      epistasis between beneficial mutations within the same lineage can further
      explain the order of mutation acquisition.

PMID- 24033183
TI  - HvZIP7 mediates zinc accumulation in barley (Hordeum vulgare) at moderately high
      zinc supply.
AB  - High expression of zinc (Zn)-regulated, iron-regulated transporter-like protein
      (ZIP) genes increases root Zn uptake in dicots, leading to high accumulation of
      Zn in shoots. However, none of the ZIP genes tested previously in monocots could
      enhance shoot Zn accumulation. In this report, barley (Hordeum vulgare) HvZIP7
      was investigated for its functions in Zn transport. The functions of HvZIP7 in
      planta were studied using in situ hybridization and transient analysis of
      subcellular localization with a green fluorescent protein (GFP) reporter.
      Transgenic barley lines overexpressing HvZIP7 were also generated to further
      understand the functions of HvZIP7 in metal transport. HvZIP7 is strongly induced
      by Zn deficiency, primarily in vascular tissues of roots and leaves, and its
      protein was localized in the plasma membrane. These properties are similar to its
      closely related homologs in dicots. Overexpression of HvZIP7 in barley plants
      increased Zn uptake when moderately high concentrations of Zn were supplied.
      Significantly, there was a specific enhancement of shoot Zn accumulation, with no
      measurable increase in iron (Fe), manganese (Mn), copper (Cu) or cadmium (Cd).
      HvZIP7 displays characteristics of low-affinity Zn transport. The unique function
      of HvZIP7 provides new insights into the role of ZIP genes in Zn homeostasis in
      monocots, and offers opportunities to develop Zn biofortification strategies in
      cereals. 

PMID- 24033184
TI  - Medical abortion: a path to safe, high-quality abortion care in Latin America and
      the Caribbean.
AB  - BACKGROUND: Abortion rates in Latin America and the Caribbean (LAC) are nearly
      triple those in Western Europe, due to less use of contraception and highly
      restrictive abortion laws. Women resort to clandestine and often unsafe methods
      to end unwanted pregnancies, exposing themselves to the risk of complications and
      mortality. Medical abortion (MA) presents a safer alternative. OBJECTIVES: To
      present evidence of MA's contributions to reduced complications, describe
      strategies to enhance safe MA, and highlight existing barriers to access in LAC,
      while examining MA's role in newly legal abortion services. RESULTS: Substantial
      declines in abortion-related morbidity and mortality and lower costs of treating
      complications are observed in LAC with MA than with other self-induction methods.
      Telephone hotlines, telemedicine and harm reduction models enhance access to
      safer abortion and help reduce complication rates by facilitating information on
      MA's proper use. Misoprostol is registered in most LAC countries, but access is
      increasingly limited by regulations and cost. CONCLUSION: Despite highly
      restrictive abortion laws in LAC, MA increases access to safer abortion. Yet,
      significant barriers remain and much more must be done to enhance use of modern
      contraceptive and safer abortion methods among women in the region.

PMID- 24033185
TI  - Impact of heart magnetic resonance imaging on chelation choices, compliance with
      treatment and risk of heart disease in patients with thalassaemia major.
AB  - This study aimed to verify the impact of heart magnetic resonance imaging on
      chelation choices and patient compliance in a single-institution cohort as well
      as its predictive value for heart failure and arrhythmias. Abnormal cardiac T2*
      values determined changes in treatment in most subjects. Heart T2* was confirmed
      to be highly predictive over 1 year for heart failure and arrhythmias. The choice
      of chelation regimens known to remove heart iron efficiently was not sufficient
      by itself to influence the risk. Compliance with treatment had a more remarkable
      role. 

PMID- 24033186
TI  - Visible-light photoredox catalysis: selective reduction of carbon dioxide to
      carbon monoxide by a nickel N-heterocyclic carbene-isoquinoline complex.
AB  - The solar-driven reduction of carbon dioxide to value-added chemical fuels is a
      longstanding challenge in the fields of catalysis, energy science, and green
      chemistry. In order to develop effective CO2 fixation, several key considerations
      must be balanced, including (1) catalyst selectivity for promoting CO2 reduction
      over competing hydrogen generation from proton reduction, (2) visible-light
      harvesting that matches the solar spectrum, and (3) the use of cheap and earth
      abundant catalytic components. In this report, we present the synthesis and
      characterization of a new family of earth-abundant nickel complexes supported by
      N-heterocyclic carbene-amine ligands that exhibit high selectivity and activity
      for the electrocatalytic and photocatalytic conversion of CO2 to CO. Systematic
      changes in the carbene and amine donors of the ligand have been surveyed, and
      [Ni((Pr)bimiq1)](2+) (1c, where (Pr)bimiq1 = bis(3
      (imidazolyl)isoquinolinyl)propane) emerges as a catalyst for electrochemical
      reduction of CO2 with the lowest cathodic onset potential (E(cat) = -1.2 V vs
      SCE). Using this earth-abundant catalyst with Ir(ppy)3 (where ppy = 2
      phenylpyridine) and an electron donor, we have developed a visible-light
      photoredox system for the catalytic conversion of CO2 to CO that proceeds with
      high selectivity and activity and achieves turnover numbers and turnover
      frequencies reaching 98,000 and 3.9 s(-1), respectively. Further studies reveal
      that the overall efficiency of this solar-to-fuel cycle may be limited by the
      formation of the active Ni catalyst and/or the chemical reduction of CO2 to CO at
      the reduced nickel center and provide a starting point for improved photoredox
      systems for sustainable carbon-neutral energy conversion.

PMID- 24033187
TI  - Laser photofabrication of cell-containing hydrogel constructs.
AB  - The two-photon polymerization (2PP) of photosensitive gelatin in the presence of
      living cells is reported. The 2PP technique is based on the localized cross
      linking of photopolymers induced by femtosecond laser pulses. The availability of
      water-soluble photoinitiators (PI) suitable for 2PP is crucial for applying this
      method to cell-containing materials. Novel PIs developed by our group allow 2PP
      of formulations with up to 80% cell culture medium. The cytocompatibility of
      these PIs was evaluated by an MTT assay. The results of cell encapsulation by 2PP
      show the occurrence of cell damage within the laser-exposed regions. However,
      some cells located in the immediate vicinity and even within the 2PP-produced
      structures remain viable and can further proliferate. The control experiments
      demonstrate that the laser radiation itself does not damage the cells at the
      parameters used for 2PP. On the basis of these findings and the reports by other
      groups, we conclude that such localized cell damage is of a chemical origin and
      can be attributed to reactive species generated during 2PP. The viable cells
      trapped within the 2PP structures but not exposed to laser radiation continued to
      proliferate. The live/dead staining after 3 weeks revealed viable cells occupying
      most of the space available within the 3D hydrogel constructs. While some of the
      questions raised by this study remain open, the presented results indicate the
      general practicability of 2PP for 3D processing of cell-containing materials. The
      potential applications of this highly versatile approach span from precise
      engineering of 3D tissue models to the fabrication of cellular microarrays. 

PMID- 24033188
TI  - In/Ga-free, inkjet-printed charge transfer doping for solution-processed ZnO.
AB  - An In/Ga-free doping method of zinc oxide (ZnO) is demonstrated utilizing a
      printable charge transfer doping layer (CTDL) based on (3
      aminopropyl)triethoxysilane (APS) molecules. The self-assembled APS molecules
      placed on top of ZnO thin films lead to n-type doping of ZnO and filling shallow
      electron traps, due to the strong electron-donating characteristics of the amine
      group in APS molecules. The CTDL doping can tune the threshold voltage and the
      mobility of the ZnO thin-film transistors (TFTs) as one varies the grafting
      density of the APS molecules and the thickness of the underneath ZnO thin films.
      From an optimized condition, high-performance ZnO TFTs can be achieved that
      exhibit an electron mobility of 4.2 cm(2)/(V s), a threshold voltage of 10.5 V,
      and an on/off current ratio larger than 10(7). More importantly, the method is
      applicable to simple inkjet processes, which lead to produce high-performance
      depletion load ZnO inverters through selective deposition of CTDL on ZnO thin
      films. 

PMID- 24033190
TI  - Zeitlupe senses blue-light fluence to mediate circadian timing in Arabidopsis
      thaliana.
AB  - Plants employ a variety of light, oxygen, voltage (LOV) domain photoreceptors to
      regulate diverse aspects of growth and development. The Zeitlupe (ZTL), Flavin
      Kelch-Fbox-1 (FKF1), and LOV-Kelch-Protein-2 (LKP2) proteins dictate measurement
      of the day length, flowering time, and regulation of the circadian clock by blue
      light regulation of protein complex formation. Previous reports indicated that
      ZTL photochemistry was irreversible, which is inconsistent with its role in
      marking the day-night transition. A kinetic model of LOV domain function predicts
      that ZTL has evolved unique photochemical parameters to allow it to function as a
      sensor of environmental light intensity. Moreover, our model indicates that a
      photocatalyzed reverse reaction is required for the sensitivity of LOV domains to
      light fluence. Inclusion of a photocatalyzed rate constant allows the
      establishment of a photostationary steady state of light-activated proteins,
      whose relative population is sensitive to daily (circadian) or positional
      (phototropism) oscillations in light intensity. Photochemical characterization
      confirms that ZTL undergoes adduct decay on a time scale of hours in contrast to
      previous reports. The fast photocycle allows detection of the day-night
      transition facilitating circadian timing. ZTL kinetics reflect an evolutionary
      adaptation of the ZTL/FKF1/LKP2 family to function in distinct aspects of blue
      light signaling. 

PMID- 24033189
TI  - Clinical outcomes of periodontal therapy are not influenced by the ATC/TTC
      haplotype in the IL8 gene.
AB  - BACKGROUND AND OBJECTIVE: Although chronic periodontitis (CP) is a multifactorial
      condition, few studies have investigated the potential association of gene
      variants with the outcome of periodontal therapy. In a previous study, we
      reported that variants in the interleukin-8 (IL8) gene were associated with CP in
      a Brazilian population. The aim of this nonrandomized study was to investigate
      whether genetic susceptibility to CP, conferred by the presence of the IL8
      ATC/TTC haplotype, influences the clinical outcomes of nonsurgical periodontal
      therapy and the IL-8 protein levels in the gingival crevicular fluid. MATERIAL
      AND METHODS: Forty-one individuals were grouped according to the presence
      (susceptible to CP; n = 21) or absence (not susceptible to CP; n = 20) of the IL8
      ATC/TTC haplotype. These individuals received nonsurgical periodontal therapy
      from one periodontist, who was blinded to the genetic status of each patient, and
      follow up continued for 45 d. The clinical parameters and gingival crevicular
      fluid samples were collected at baseline and on day 45. The IL-8 levels were
      determined by an ELISA. The data were subjected to the Mann-Whitney U-test,
      Wilcoxon and Spearman tests and to multiple logistic-regression analysis.
      RESULTS: No significant differences between patients with or without the IL8
      ATC/TTC haplotype were found for the outcome of nonsurgical periodontal therapy
      and IL-8 levels. The multiple logistic-regression analysis did not show a
      statistically significant association between the IL8 haplotype and the variables
      studied. CONCLUSION: In this longitudinal clinical study, we observed that
      neither the outcome of nonsurgical periodontal therapy nor the IL-8 levels were
      influenced by the IL8 ATC/TTC CP-susceptibility haplotype. Additional studies of
      CP patients from other ethnic populations are necessary to confirm these results.

PMID- 24033191
TI  - Spaceflight environment induces mitochondrial oxidative damage in ocular tissue.
AB  - A recent report shows that more than 30% of the astronauts returning from Space
      Shuttle missions or the International Space Station (ISS) were diagnosed with eye
      problems that can cause reduced visual acuity. We investigate here whether
      spaceflight environment-associated retinal damage might be related to oxidative
      stress-induced mitochondrial apoptosis. Female C57BL/6 mice were flown in the
      space shuttle Atlantis (STS-135), and within 3-5 h of landing, the spaceflight
      and ground-control mice, similarly housed in animal enclosure modules (AEMs) were
      euthanized and their eyes were removed for analysis. Changes in expression of
      genes involved in oxidative stress, mitochondrial and endothelial cell biology
      were examined. Apoptosis in the retina was analyzed by caspase-3
      immunocytochemical analysis and terminal deoxynucleotidyl transferase-mediated
      dUTP nick-end labeling (TUNEL) assay. Levels of 4-hydroxynonenal (4-HNE) protein,
      an oxidative specific marker for lipid peroxidation were also measured.
      Evaluation of spaceflight mice and AEM ground-control mice showed that expression
      of several genes playing central roles in regulating the mitochondria-associated
      apoptotic pathway were significantly altered in mouse ocular tissue after
      spaceflight compared to AEM ground-control mice. In addition, the mRNA levels of
      several genes, which are responsible for regulating the production of reactive
      oxygen species were also significantly up-regulated in spaceflight samples
      compared to AEM ground-control mice. Further more, the level of HNE protein was
      significantly elevated in the retina after spaceflight compared to controls. Our
      results also revealed that spaceflight conditions induced significant apoptosis
      in the retina especially inner nuclear layer (INL) and ganglion cell layer (GCL)
      compared to AEM ground controls. The data provided the first evidence that
      spaceflight conditions induce oxidative damage that results in mitochondrial
      apoptosis in the retina. This data suggest that astronauts may be at increased
      risk for late retinal degeneration. 

PMID- 24033192
TI  - Changes of reactive oxygen and nitrogen species and mitochondrial functioning in
      human K562 and HL60 cells exposed to ionizing radiation.
AB  - Free radicals generated by mitochondria are candidates for mediating long-lasting
      effects of radiation on cells, including genetic instability. To better
      understand the significance of reactive oxygen species (ROS) and reactive
      nitrogen species (RNS) in these long-term effects we assayed ROS and RNS levels,
      the mitochondrial membrane potential and mass, and the frequency of DNA strand
      breaks, apoptosis and necrosis in human leukemic cells (K562 and HL60) after 12
      Gy of X irradiation. An increase in intracellular ROS level was observed
      immediately post-irradiation, and about 24 h later a second increase of ROS was
      accompanied by increase in nitrogen oxide, mitochondrial potential and
      mitochondrial mass in both cell types. The second peak of ROS level was partially
      inhibited by rotenone, an inhibitor of mitochondrial complex I, in K562 but not
      in HL60 cells suggesting that the sources of ROS differed in the two cell types.
      The frequency of DNA breaks showed kinetics similar to ROS levels, with a sharp
      peak immediately after irradiation and a second increase 24 and 48 h later, which
      was significantly higher in K562 cells. Forty-eight hours after irradiation an
      increase in the frequency of apoptotic cells was observed in both cell lines,
      which became larger and statistically significant in K562 cells after inhibition
      of mitochondrial complex I. Our results show that ionizing radiation activates
      cellular processes which produce long-lasting ROS and RNS radicals, which may
      have different sources in different cell types and could participate in cellular
      signaling networks important for radiosensitivity and mode of cell death. 

PMID- 24033193
TI  - Australia's leadership in developing goals for sustainable global health.

PMID- 24033194
TI  - Doctors, death certificates and reporting to coroners - room for improvement.

PMID- 24033195
TI  - Can professionalism be taught?

PMID- 24033196
TI  - Pyoderma gangrenosum - a frequently misdiagnosed skin condition.

PMID- 24033199
TI  - Legislate for patient-delivered partner therapy for chlamydia.

PMID- 24033200
TI  - The after-life of drugs: a responsible care initiative for reducing their
      environmental impact.

PMID- 24033201
TI  - Further erosion of equality and job mobility of Australian junior doctors.

PMID- 24033202
TI  - Junior doctors leading hospital improvement.

PMID- 24033203
TI  - Risk of measles transmission on aeroplanes: Australian experience 2007-2011.

PMID- 24033205
TI  - Modifying the gluten-free threshold for foods: first do no harm.

PMID- 24033206
TI  - Diet and nutrition: the folly of the reductionist approach.

PMID- 24033207
TI  - Vitamin D and health in adults in Australia and New Zealand.

PMID- 24033208
TI  - Vitamin D and health in adults in Australia and New Zealand.

PMID- 24033209
TI  - Trends in amphetamine-related harms in Victoria.

PMID- 24033210
TI  - Sharper tools - chronic conditions and avoidable admission.

PMID- 24033211
TI  - Attitudes of a private hospital community to medical student teaching.

PMID- 24033212
TI  - Clinical transfusion practice update: haemovigilance, complications, patient
      blood management and national standards.
AB  - Blood transfusion is not without risk. Although the risks of HIV and hepatitis
      transmission have diminished, haemovigilance programs highlight that other
      significant transfusion hazards remain. Sepsis from bacterial contamination is
      the most common residual infectious hazard in developed countries, and events due
      to clerical error are problematic. Unnecessary transfusions should be avoided.
      New national guidelines on patient blood management (PBM) emphasise holistic
      approaches, including strategies to reduce transfusion requirements.
      Perioperative PBM should incorporate preoperative haemoglobin and medication
      optimisation, intraoperative blood conservation, and consideration of restrictive
      postoperative transfusion and cell-salvage techniques. When massive transfusion
      is required, hospitals should implement massive transfusion protocols. These
      protocols reduce mortality, improve communication and facilitate adequate
      provision of blood products. They should include multidisciplinary team
      involvement and guidelines for use of blood components and adjunctive agents.
      Although fresh frozen plasma to red blood cell and platelet to red blood cell
      ratios of >= 1 : 2 appear to reduce mortality in trauma patients who receive
      massive transfusion, there is insufficient evidence to recommend specific ratios.
      Systematic reviews have found no significant benefit of recombinant activated
      factor VII in critical bleeding, and an increase in thromboembolic events;
      specialist haematology advice is therefore recommended when considering use of
      this agent. The National Safety and Quality Health Service Standards address use
      of blood and blood products, and provide important transfusion principles for
      adoption by all clinicians. Storage of red cells in additive solution results in
      changes, known as the "storage lesion", and studies to determine the clinical
      effect of the age of blood at transfusion are ongoing. 

PMID- 24033213
TI  - Non-reporting of reportable deaths to the coroner: when in doubt, report.
AB  - OBJECTIVE: To better understand the non-reporting of reportable deaths by
      determining the frequency and nature of reportable deaths referred to the
      Coroners Court of Victoria (CCOV) by the Registry of Births, Deaths and Marriages
      (BDM). DESIGN AND SETTING: Review of referrals from BDM to the CCOV between 2003
      and 2011 where an external cause of death was recorded on the death certificate,
      with detailed review for the period 1 July 2010 to 30 June 2011. MAIN OUTCOME
      MEASURES: Frequency and nature of deaths referred, accuracy of cause of death
      recorded on death certificate, and degree of change made to cause of death after
      investigation. RESULTS: Over 9 years, there were 4283 referrals (annual mean,
      476). Of 656 deaths referred between 1 July 2010 and 30 June 2011, 320 (48.8%)
      were found to be reportable. Most causes of death related to injuries; less
      common were choking, deaths after medical procedures, poisoning and transport
      related deaths. Most of the deceased were women (55.9%), were aged >= 80 years
      (80.0%), and died in hospital (68.4%). In 309 cases (96.6%), the coroner changed
      the cause of death after investigation, with a major change in 146 (45.6%), minor
      change in 160 (50.0%), and deletion of comorbidities in three (0.9%). Twenty-one
      cases (6.6%) were investigated further, with one proceeding to an inquest.
      CONCLUSIONS: Deaths referred by BDM represent a proportion of the unquantified
      pool of non-reported deaths. Non-reporting of potentially reportable deaths and
      inaccurate completion of death certificates have significant implications for the
      health system and community. Further education of medical practitioners about
      reportable deaths and death certificates is required. Doctors should report any
      death about which they have doubt.

PMID- 24033214
TI  - "They liked it if you said you cried": how medical students perceive the teaching
      of professionalism.
AB  - OBJECTIVE: To discover what Australian medical students think about the way
      professionalism is taught in their medical curriculum. DESIGN, PARTICIPANTS AND
      SETTING: Qualitative study including five focus groups between 2 June 2010 and 30
      September 2010, comprised of medical students from both undergraduate and
      postgraduate entry programs who were in the last 1-2 years of the medical program
      and had undertaken rural longitudinal integrated clinical placements. RESULTS:
      The five focus groups ran for a total of 5.5 hours. Participants (16 women and 24
      men; mean age, 26 years [range 23-32 years]) expressed a low regard for the ways
      in which professionalism had been taught and assessed in their learning programs.
      They "gamed the system", giving assessors the results on reflective writing
      assignments that they believed would gain them a pass. They considered
      experiential learning - observing good professional practice - to be the best way
      (some view it as the only way) to learn professionalism and consolidate what they
      learned, and formed their individual mental model of professionalism through
      group reflection with their peers in medical school. CONCLUSIONS: While students
      will always be critical of their curriculum, the universal negative views we
      captured indicate that current teaching would benefit from review. We suggest a
      less didactic approach in early years, with more evaluation and feedback from
      students to assure relevance; an emphasis on true reflection, as opposed to
      guided reflections linked to overformalised requirements; and more attention
      devoted to role-modelling and mentoring in the clinical years of training.

PMID- 24033215
TI  - Asbestos exposure during home renovation in New South Wales.
AB  - OBJECTIVE: Asbestos exposure is causally associated with the development of
      malignant mesothelioma (MM), which is increasingly being reported after exposure
      to asbestos fibro sheeting in Australia. In this study, we investigate self
      reported non-occupational asbestos exposure during home renovation in New South
      Wales. DESIGN AND SETTING: Cross-sectional mailed questionnaire examining
      renovation activity, tasks undertaken during renovation and self-reported
      exposure to asbestos among respondents and their family members in NSW between
      January and June 2008. PARTICIPANTS: 10 000 adults aged 18-99 years, randomly
      selected from the NSW electoral roll. We received 3612 responses, while 365
      questionnaires did not reach addressees, giving an overall response rate of
      37.5%. MAIN OUTCOME MEASURES: Differences in self-reported asbestos exposure
      between do-it-yourself (DIY) and non-DIY renovators. RESULTS: 1597 participants
      (44.2%) had renovated their home and among these, 858 participants (53.7%) self
      reported as DIY renovators. Of these, 527 (61.4%) reported asbestos exposure
      during home renovations, 337 (39.3%) reported that their partner had been exposed
      to asbestos during renovations, and 196 (22.8%) reported that their children had
      been exposed. More than 20% of renovators planned to further renovate their
      current homes within the next 5 years. CONCLUSIONS: Self-reported asbestos
      exposure during home renovation is common. This preventable exposure could place
      adults and children at risk of MM many years into the future. Although such
      exposure is self-reported and ideally should be verified, this study identifies a
      potentially important problem in NSW.

PMID- 24033216
TI  - Cost savings from a telemedicine model of care in northern Queensland, Australia.
AB  - OBJECTIVE: To conduct a cost analysis of a telemedicine model for cancer care
      (teleoncology) in northern Queensland, Australia, compared with the usual model
      of care from the perspective of the Townsville and other participating hospital
      and health services. DESIGN: Retrospective cost-savings analysis; and a one-way
      sensitivity analysis performed to test the robustness of findings in net savings.
      PARTICIPANTS AND SETTING: Records of all patients managed by means of
      teleoncology at the Townsville Cancer Centre (TCC) and its six rural satellite
      centres in northern Queensland, Australia between 1 March 2007 and 30 November
      2011. MAIN OUTCOME MEASURES: Costs for set-up and staffing to manage the service,
      and savings from avoidance of travel expenses for specialist oncologists,
      patients and their escorts, and for aeromedical retrievals. RESULTS: There were
      605 teleoncology consultations with 147 patients over 56 months, at a total cost
      of $442 276. The cost for project establishment was $36 000,
      equipment/maintenance was $143 271, and staff was $261 520. The estimated travel
      expense avoided was $762 394; this figure included the costs of travel for
      patients and escorts of $658 760, aeromedical retrievals of $52 400 and travel
      for specialists of $47 634, as well as an estimate of accommodation costs for a
      proportion of patients of $3600. This resulted in a net saving of $320 118. Costs
      would have to increase by 72% to negate the savings. CONCLUSION: The teleoncology
      model of care at the TCC resulted in net savings, mainly due to avoidance of
      travel costs. Such savings could be redirected to enhancing rural resources and
      service capabilities. This teleoncology model is applicable to geographically
      distant areas requiring lengthy travel.

PMID- 24033217
TI  - Quad bike related injury in Victoria, Australia.
AB  - OBJECTIVE: To enumerate and describe fatal and hospital-treated injury associated
      with quad bike use in Victoria. DESIGN: Retrospective descriptive analysis of
      coronial records and hospital-treated injury data (2002-03 to 2010-11). MAIN
      OUTCOME MEASURES: Number of quad bike-related fatalities, hospital admissions,
      emergency department (ED) presentations, and results of a trend and severity
      analysis (International Classification of Disease-based Injury Severity Score;
      ICISS). RESULTS: There were 19 fatalities, 766 hospital admissions and 816 ED
      presentations. The peak age group for fatalities and admissions was 15-29 years
      (26.3% and 27.9%, respectively), with children 0-14 years being the most common
      group presenting to EDs (32.2%). Males were strongly overrepresented (84.2% of
      fatalities, 73.8% of admissions and 71.2% of ED presentations). Intracranial
      injury (26.3%), fractures (15.8%) and traumatic asphyxiation (15.8%) were the
      most common injuries among fatal cases. Fractures accounted for half all
      admissions. Twenty-eight per cent of admissions were classified as "serious"
      (ICISS, <= 0.941) and, over the 9-year study period, the frequency of admissions
      increased significantly by an estimated 41.4% (95% CI, 9.6%-78.9%). This was
      significant for males (53.2%; 95% CI, 11.5%-104.4%) and people aged 15-29 years
      (163.1%; 95% CI, 75.2%-253.7%). CONCLUSION: Quad bikes are imposing a significant
      injury burden in Victoria. Fatalities are frequent, while the number of
      admissions, often serious, increased over the study period. Children were
      involved across all levels of severity. A range of prevention approaches, such as
      mandatory fitting of crush protection devices to protect riders in the event of a
      roll over, are required.

PMID- 24033218
TI  - First report of probable neurobrucellosis in Australia.
AB  - We report the first known Australian case of probable neurobrucellosis, in a
      young feral-pig shooter who presented with episodic left-sided visual loss and
      left-sided numbness and headache. Treatment with intravenous ceftriaxone and oral
      rifampicin, doxycycline and trimethoprim-sulfamethoxazole resulted in a good
      clinical response.

PMID- 24033219
TI  - MJA, MDA National, Nossal Global Health Prize - Utilising humanism to (re)fortify
      global health leadership.

PMID- 24033220
TI  - Acute onset of lower limb weakness, sphincter dysfunction and sensory disturbance
      in an older woman.

PMID- 24033221
TI  - Dynamics of macronutrient self-medication and illness-induced anorexia in virally
      infected insects.
AB  - Some animals change their feeding behaviour when infected with parasites, seeking
      out substances that enhance their ability to overcome infection. This 'self
      medication' is typically considered to involve the consumption of toxins,
      minerals or secondary compounds. However, recent studies have shown that
      macronutrients can influence the immune response and that pathogen-challenged
      individuals can self-medicate by choosing a diet rich in protein and low in
      carbohydrates. Infected individuals might also reduce food intake when infected
      (i.e. illness-induced anorexia). Here, we examine macronutrient self-medication
      and illness-induced anorexia in caterpillars of the African armyworm (Spodoptera
      exempta) by asking how individuals change their feeding decisions over the time
      course of infection with a baculovirus. We measured self-medication behaviour
      across several full-sib families to evaluate the plasticity of diet choice and
      underlying genetic variation. Larvae restricted to diets high in protein (P) and
      low in carbohydrate (C) were more likely to survive a virus challenge than those
      restricted to diets with a low P : C ratio. When allowed free choice, virus
      challenged individuals chose a higher protein diet than controls. Individuals
      challenged with either a lethal or sublethal dose of virus increased the P : C
      ratio of their chosen diets. This was mostly due to a sharp decline in
      carbohydrate intake, rather than an increased intake of protein, reducing overall
      food intake, consistent with an illness-induced anorexic response. Over time the
      P : C ratio of the diet decreased until it matched that of controls. Our study
      provides the clearest evidence yet for dietary self-medication using
      macronutrients and shows that the temporal dynamics of feeding behaviour depends
      on the severity and stage of the infection. The strikingly similar behaviour
      shown by different families suggests that self-medication is phenotypically
      plastic and not a consequence of genetically based differences in diet choice
      between families.

PMID- 24033222
TI  - Motivated by meaning: testing the effect of knowledge-infused rewards on
      preschoolers' persistence.
AB  - Research and theory suggest that young children are highly attuned to causality.
      This study explores whether this drive can motivate task engagement. Fifty-six 3-
      and 4-year-olds completed a motor task as many times as desired, viewing a
      picture of a novel item upon each completion. Forty-two randomly assigned
      children then received either: (a) causally rich information regarding the item,
      (b) causally weak information regarding the item, or (c) a tangible reward. The
      remaining 14 children participated in a baseline condition featuring no rewards.
      Preschoolers completed more trials when rewarded with causally rich than causally
      weak information, or when given no reward. Children also trended toward lengthier
      persistence in the causally rich than the tangible reward condition. Implications
      for theory and educational practice are discussed. 

PMID- 24033223
TI  - A comprehensive survey of both RHD and RHCE allele frequencies in sub-Saharan
      Africa.
AB  - BACKGROUND: The RH system is one of the most polymorphic blood group systems with
      numerous allele variants affecting Rh polypeptides expression. This complexity is
      at the origin of difficulties for transfusion of African patients especially
      sickle cell disease patients requiring chronic transfusion therapy with high risk
      of immunization. As a complete survey of RH variants is lacking in African
      populations, we performed red blood cell genotyping to determine the type and
      frequency of RHD and RHCE alleles in sub-Saharan African populations. STUDY
      DESIGN AND METHODS: A total of 347 blood samples were collected from individuals
      of six nonpygmoid and three pygmoid populations. RH typing was performed using
      two single-tube multiplex polymerase chain reaction amplifications (BioArray
      Solutions, Immucor). RESULTS: All six sub-Saharan nonpygmoid populations
      exhibited constant variety in both type and frequency of aberrant RHD and RHCE
      alleles. Predicted partial RH1 (1.8%) and RH5 (0.9%) phenotypes were less than
      expected. Conversely, predicted partial phenotype RH2 (5.5%) was frequent. Data
      confirmed the high frequency of samples positive for the non-clinically
      significant RH10/RH20 antigens (39.5%) and revealed a high frequency of RH54
      (DAK, 8.1%). The pygmoid groups showed higher percentages of predicted partial RH
      antigens and greater heterogeneity reflecting wide genetic differentiation.
      CONCLUSION: Our data show that frequencies of aberrant RHD and RHCE alleles were
      similar, irrespective of location and ethnicity. In view of the predicted
      frequencies and relative clinical significance of both private antigens and high
      prevalence antigens absent, the most relevant assays for individuals of African
      descent in a transfusion setting are for 1) partial RH2 in the patient and 2)
      RH54 (DAK) in the donor.

PMID- 24033224
TI  - Synthesis, Characterization and Photocatalytic Activity of Mg-Impregnated ZnO
      SnO2 Coupled Nanoparticles.
AB  - ZnO-SnO2 nanoparticles were prepared by coprecipitation method; then Mg, with
      different molar ratios and calcination temperatures, was loaded on the coupled
      nanoparticles by impregnation method. The synthesized nanoparticles were
      characterized by X-ray diffraction (XRD), field emission scanning electron
      microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX), transmission
      electron microscopy (TEM), diffuse reflectance spectroscopy (DRS), and Brunauer
      Emmett-Teller (BET) techniques. Based on XRD results, the ZnO-SnO2 and Mg/ZnO
      SnO2 nanoparticles were made of ZnO and SnO2 nanocrystallites. According to DRS
      spectra, the band gap energy value of 3.13 and 3.18 eV were obtained for ZnO-SnO2
      and Mg/ZnO-SnO2 nanoparticles, respectively. BET analysis revealed a Type III
      isotherm with a microporous structure and surface area of 32.051 and 49.065 m(2) 
      g(-1) for ZnO-SnO2 and Mg/ZnO-SnO2 , respectively. Also, the spherical shape of
      nanocrystallites was deduced from TEM and FESEM images. The photocatalytic
      performance of pure ZnO-SnO2 and Mg/ZnO-SnO2 was analyzed in the photocatalytic
      removal of methyl orange (MO). The results indicated that Mg/ZnO-SnO2 exhibited
      superior photocatalytic activity to bare ZnO-SnO2 photocatalyst due to high
      surface area, increased MO adsorption and larger band gap energy. Maximum
      photocatalytic activity of Mg/ZnO-SnO2 nanoparticles was obtained with 0.8 mol%
      Mg and calcination temperature of 350 degrees C.

PMID- 24033225
TI  - Hydroxysafflor yellow A attenuates left ventricular remodeling after pressure
      overload-induced cardiac hypertrophy in rats.
AB  - CONTEXT: Hydroxysafflor yellow A (HSYA), the main chemical component of the
      safflower yellow pigments, is used extensively in traditional Chinese medicine
      for the treatment of cerebrovascular and cardiovascular diseases. OBJECTIVE: The
      present study determined the effects of HSYA on left ventricular hypertrophy
      after pressure overload and investigated the underlying mechanisms. MATERIALS AND
      METHODS: Cardiac hypertrophy was induced by the ligation of abdominal aorta in
      male Wistar rats. The rats were then divided into five groups and treated with
      captopril (100 mg/kg) or HSYA at different doses (0, 10, 20 and 40 mg/kg). Six
      weeks after treatment, the weight of left ventricle, LVMI (left ventricular mass
      index) and pathological changes were measured. MMP-2 (metalloproteinase 2) and
      MMP-9 (metalloproteinase 9) levels were determined by ELISA. Protein expressions
      of Bcl-2 and Bax were evaluated by immunohistochemistry. RESULTS: HSYA (20, 40
      mg/kg) significantly attenuated the increase of LVMI (ventricular weight/body
      weight) by 13.04 and 30.43% respectively, when compared with the model group.
      This was associated with the amelioration of pathological lesion, such as cardiac
      muscle fibers were smaller and the nuclei of cardiomyocytes were lightly stained
      in animals treated with HSYA (20, 40 mg/kg). In addition, the administration of
      HSYA at doses of 20 and 40 mg/kg increased the Bcl-2/Bax ratio (1.17 +/- 0.08 and
      1.39 +/- 0.07 versus 0.71 +/- 0.06). In addition, the serum MMP-2 and MMP-9
      levels were blocked by the treatment at doses of 20 and 40 mg/kg HSYA (MMP-2,
      76.1 +/- 9.2 and 65.6 +/- 6.8 versus 82.9 +/- 6.2, ng/ml; MMP-9, 66.6 +/- 4.8 and
      57.5 +/- 5.0 versus 83.5 +/- 6.0, ng/ml). CONCLUSION: These findings indicated
      that HSYA has beneficial effects on hypertensive ventricular remodeling, which
      may involve mechanisms of inhibiting cell apoptosis and suppressing
      metalloproteinases expression.

PMID- 24033226
TI  - Multiscale simulation of the ground and photo-induced charge-separated states of
      a molecular triad in polar organic solvent: exploring the conformations,
      fluctuations, and free energy landscapes.
AB  - The approach of a multiscale simulation that combines quantum chemical
      calculations, classical molecular dynamics simulations, and statistical physics
      to integrate the information of the electronic states of a conformationally
      complex molecule into its structural distribution over an ensemble was performed
      to understand the influence of a polar organic solvent on the structural
      stability of carotene-porphyrin-fullerene molecular triad in both the ground and
      the photoinduced charge-separated excited states. The excited states of the triad
      were computed with the ab initio quantum chemical calculations using the
      algebraic diagrammatic construction through the second order correction (ADC(2))
      method and the time-dependent density functional theory (TDDFT). The replica
      exchange molecular dynamics was used for the enhanced sampling of the ensemble in
      order to explore the phase space of the ground state and the photoinduced charge
      separated excited state of triad in explicit tetrahydrofuran (THF) solvent. An
      importance sampling was strategically employed to bridge the gap between the two
      computational methods that aim to explore distinct realms of dynamics. We
      analyzed the free energy landscape, the structural fluctuations, the solvent
      arrangements, the static dielectric constant, and the interactions between the
      triad and the solvent molecules. The analysis of the free energy landscape of the
      triad indicates that the charge-separated excited state of the triad is
      thermodynamically stable in a linearly extended geometry, while the ground-state
      triad explores several extended and bent conformations that are populated in the
      local free energy minima separated by low free energy barriers at an order of
      thermal fluctuation (k(B)T). The stabilization of a linearly extended structure
      of the charge-separated excited state triad is predominantly due to the solvation
      interactions (van der Waals and electrostatic interactions) between the triad and
      the THF molecules as well as the interactions within the THF molecules.
      Differences in the charge distribution on a molecular triad induce slight changes
      in the dielectric property of THF near the triad. Our study suggests that by
      measuring the differences in a dielectric response of solvent near the triad, it
      is possible to provide insight into the population of the charge-separated
      electronic state of the triad relative to that of the ground state.

PMID- 24033227
TI  - Measurement of steroid hormones in saliva: Effects of sample storage condition.
AB  - Measurement of steroid hormones in saliva is increasingly common in elite sport
      settings. However, this environment may enforce handling and storage practices
      that introduce error in measurement of hormone concentrations. We assessed the
      influence of storage temperature and duration on reproducibility of salivary
      steroid levels. Nine healthy adults provided morning and afternoon saliva samples
      on two separate occasions. Each sample was divided into identical saliva aliquots
      which were stored long-term (i.e. 28 and 84 days) at - 80 degrees C or - 20
      degrees C (testing day 1), and short-term (i.e. 1, 3, 7 and 14 days) at 4 degrees
      C or 20 degrees C (testing day 2). Samples were analyzed for cortisol,
      testosterone and estradiol using ELISA. In non-freezer conditions, there was a
      decrease from baseline to 7 days in testosterone (- 26 +/- 15%) and estradiol (-
      58 +/- 17%) but not cortisol concentrations (p < 0.001). This decrease was larger
      in samples stored at room temperature than in the refrigerator (p <= 0.01). There
      were small but significant changes in measured concentrations of all hormones
      after 28 and/or 84 days of storage in freezer conditions (p <= 0.01), but these
      were generally within 12% of baseline concentrations, and may be partly explained
      by inter-assay variability. Whole saliva samples to be analyzed for cortisol,
      testosterone and estradiol should be frozen at - 20 degrees C or below within 24
      h of collection, and analyzed within 28 days. Storage of samples for measurement
      of testosterone and estradiol at temperatures above - 20 degrees C can introduce
      large error variance to measured concentrations.

PMID- 24033228
TI  - Experienced continuity of care in patients at risk for depression in primary
      care.
AB  - BACKGROUND: Existing studies about continuity of care focus on patients with a
      severe mental illness. OBJECTIVES: Explore the level of experienced continuity of
      care of patients at risk for depression in primary care, and compare these to
      those of patients with heart failure. METHODS: Explorative study comparing
      patients at risk for depression with chronic heart failure patients. Continuity
      of care was measured using a patient questionnaire and defined as ( 1 ) number of
      care providers contacted (personal continuity); ( 2 ) collaboration between care
      providers in general practice (team continuity) (six items, score 1-5); and ( 3 )
      collaboration between GPs and care providers outside general practice (cross
      boundary continuity) (four items, score 1-5). RESULTS: Most patients at risk for
      depression contacted several care providers throughout the care spectrum in the
      past year. They experienced high team continuity and low cross-boundary
      continuity. In their general practice, they contacted more different care
      providers for their illness than heart failure patients did (P < 0.01). Patients
      at risk for depression experienced a slightly better collaboration between these
      care providers in their practice: a mean score of 4.3 per item compared to 4.0
      for heart failure patients (P = 0.03). The perceived cross-boundary continuity,
      however, was reversed: a mean score of 3.5 per item for patients at risk for
      depression, compared to 4.0 for heart failure patients (P = 0.01). CONCLUSION:
      The explorative comparison between patients at risk for depression and heart
      failure patients shows small differences in experienced continuity of care. This
      should be analysed further in a more robust study.

PMID- 24033229
TI  - Bipolar disease and excess mortality - is 'hidden' glucose part of the game?

PMID- 24033230
TI  - Parental attitudes, values, and beliefs toward the return of results from exome
      sequencing in children.
AB  - Exome sequencing is being offered for children with undiagnosed conditions to
      identify a primary (causative) variant. Parental preferences for learning
      secondary (incidental) variants are largely unexplored. Our objective was to
      characterize values and beliefs that shape parents' preferences for learning
      their children's sequencing results. We conducted semi-structured interviews with
      25 parents of 13 minor probands with a variety of rare genetic conditions.
      Parents were asked to discuss their preferences to receive four types of results
      from exome sequencing. Many parents preferred to receive all types of results.
      Parents had the most positive attitudes toward learning about variants that
      predispose to disorders treatable or preventable in childhood. They had
      reservations about learning about predispositions for untreatable adult-onset
      conditions and carrier status for recessive conditions. Parents described their
      success in coping with their child's condition as evidence for an ability to
      manage any additional negative health information. They felt responsible for
      learning about secondary variants, desiring a gain in control over their child's
      health. Our findings suggest that investigators should incorporate parents'
      perceptions of the value in receiving secondary variant information about their
      children when designing studies employing exome sequencing. 

PMID- 24033231
TI  - Sequencing of a novel HLA-B allele, B*51:153, in a Spanish individual.
AB  - HLA-B*51:153 shows two nucleotide differences compared with B*51:08 at codon 163
      (CTG>ACG).

PMID- 24033232
TI  - Reinterpreting the mechanism of inhibition of Mycobacterium tuberculosis D
      alanine:D-alanine ligase by D-cycloserine.
AB  - d-Cycloserine is a second-line drug approved for use in the treatment of patients
      infected with Mycobacterium tuberculosis, the etiologic agent of tuberculosis.
      The unique mechanism of action of d-cycloserine, compared with those of other
      clinically employed antimycobacterial agents, represents an untapped and
      exploitable resource for future rational drug design programs. Here, we show that
      d-cycloserine is a slow-onset inhibitor of MtDdl and that this behavior is
      specific to the M. tuberculosis enzyme orthologue. Furthermore, evidence is
      presented that indicates d-cycloserine binds exclusively to the C-terminal d
      alanine binding site, even in the absence of bound d-alanine at the N-terminal
      binding site. Together, these results led us to propose a new model of d
      alanine:d-alanine ligase inhibition by d-cycloserine and suggest new
      opportunities for rational drug design against an essential, clinically validated
      mycobacterial target. 

PMID- 24033234
TI  - Editorial: programs for strengthening families.

PMID- 24033233
TI  - Changes in angiogenesis and hypoxia-inducible factor-1alpha protein expression in
      relapsed/refractory indolent non-Hodgkin lymphomas.
AB  - Angiogenesis is involved in the pathogenesis and progression of non-Hodgkin
      lymphomas (NHL), and hypoxia-inducible factor-1alpha (HIF-1alpha, also termed
      HIF1A) might contribute to this process. Currently, there is no direct evidence
      that the clinical progression of indolent NHL is associated with angiogenesis,
      and the expression of HIF-1alpha at recurrence is unknown. Matched lymph node
      biopsies at diagnosis and recurrence of relapsed/refractory indolent NHL patients
      were analysed by immunohistochemical and morphometric analysis. We observed an
      increased vascular network and HIF-1alpha protein expression in the second
      biopsy, providing direct evidence that angiogenesis is an essential process for
      disease progression. 

PMID- 24033235
TI  - In the wake of violence: enacting and witnessing hope among people.
AB  - In the territory of violence and despair, hope is rare. Recent work on hope has
      shifted attention from hope as a feeling to hope as a practice that people can do
      together. This case report of a family exposed to domestic violence highlights
      the role played by a South African police officer in the mother's actions to
      separate from the context of violence. As a witness to the violence, the police
      officer acted from an ethic of justice and an ethic of compassion. Outsider
      witnessing of a counseling session resulted in the recruiting of a community of
      acknowledgement for the mother, the police officer, and an Assistant Commissioner
      of Police. Listening carefully and doing hope together gave rise to alliances
      against practices of violence. As a step of accountability, the authors used
      reflexive practices to question their responses and to avoid colonizing
      practices. 

PMID- 24033236
TI  - Couples therapy with childhood sexual abuse survivors (CSA) and their partners:
      establishing a context for witnessing.
AB  - This article proposes a clinical practice for therapy with couples in which one
      partner suffered sexual abuse in childhood. Such couples often encounter unique
      difficulties with physical contact, intimacy, sexuality, communication, and
      trust, and their relationship dynamic may be marked by reenactments of past
      traumatic relational patterns. This clinical practice is founded on the
      assumption that establishing the witnessing lacking during the traumatic event in
      childhood can break the traumatic reenactments in adulthood, and spur recovery.
      The suggested practice may facilitate twofold witnessing: the couple's therapist
      witnesses the reenactments of the trauma in the couple's relationship; and the
      survivor's partner witnesses the trauma's effect on the survivor's personal life
      and relationship. Twofold witnessing can help break the cycle of traumatic
      reenactment and help the survivor integrate the events of her life into a more
      coherent, continuous narrative. The partner's presence also facilitates
      acknowledgement of what happened to the survivor, and helps the survivor
      elaborate on her stories of resistance, survival, and strength. Finally, each of
      the partners is able to appear more wholly and fully, and together to tell the
      preferred stories of their life as a couple, replete with the multiple relational
      patterns they wish to live, which may contradict the characteristics of the
      original trauma. 

PMID- 24033237
TI  - Fortalezas familiares program: building sociocultural and family strengths in
      latina women with depression and their families.
AB  - The purpose of this article is to describe Fortalezas Familiares (FF; Family
      Strengths), a community-based prevention program designed to address relational
      family processes and promote well-being among Latino families when a mother has
      depression. Although depression in Latina women is becoming increasingly
      recognized, risk and protective mechanisms associated with children's outcomes
      when a mother has depression are not well understood for Latino families. We
      begin by reviewing the literature on risk and protective psychosocial mechanisms
      by which maternal depression may affect Latino youth, using family systems theory
      and a developmental psychopathology framework with an emphasis on sociocultural
      factors shaping family processes. Next, we describe the theoretical basis and
      development of the FF program, a community-based 12-week intervention for Latina
      immigrant women with depression, other caregivers, and their children. Throughout
      this article, we use a case study to illustrate a Latina mother's vulnerability
      to depression and the family's response to the FF program. Recommendations for
      future research and practice include consideration of sociocultural processes in
      shaping both outcomes of Latino families and their response to interventions. 

PMID- 24033238
TI  - Feasibility, acceptability, and preliminary outcomes of the Fortalezas Familiares
      intervention for latino families facing maternal depression.
AB  - This pilot study examined the feasibility, acceptability, and preliminary
      outcomes of a linguistically and culturally adapted intervention for immigrant
      Latina mothers with depression and their families. Fortalezas Familiares (Family
      Strengths) is a community-based, 12-week, multifamily group intervention that
      aims to increase communication about family processes leading up to and affected
      by the mother's depression, build child coping and efficacy, enhance parenting
      competence and skills, and promote cultural and social assets within the family.
      In terms of feasibility, of 16 families who enrolled and participated in the
      intervention, 13 families attended more than 90% of meetings and completed the
      intervention. Posttests reported positive changes following the intervention,
      including improved psychological functioning, increased family and marital
      support, and enhanced family functioning, as reported by mothers and other
      caregivers. Mothers also reported decreased conduct and hyperactivity problems
      among their children. Children reported positive changes in their psychological
      functioning and coping, parenting warmth and acceptance, and overall family
      functioning. Postintervention focus groups and surveys measuring acceptability
      revealed families' satisfaction with the intervention and suggested areas of
      improvement. We discuss similarities and differences in outcomes between the
      adapted intervention, Fortalezas Familiares, and the original intervention,
      Keeping Families Strong, and propose future areas of intervention adaptation and
      development. 

PMID- 24033239
TI  - A randomized controlled trial of group Stepping Stones Triple P: a mixed
      disability trial.
AB  - Stepping Stones Triple P (SSTP) is a parenting program designed for families of a
      child with a disability. The current study involved a randomized controlled trial
      of Group Stepping Stones Triple P (GSSTP) for a mixed-disability group.
      Participants were 52 families of children diagnosed with an Autism Spectrum
      Disorder, Down syndrome, Cerebral Palsy, or an intellectual disability. The
      results demonstrated significant improvements in parent-reported child behavior,
      parenting styles, parental satisfaction, and conflict about parenting. Results
      among participants were similar despite children's differing impairments. The
      intervention effect was maintained at 6-month follow-up. The results indicate
      that GSSTP is a promising intervention for a mixed-disability group. Limitations
      of the study, along with areas for future research, are also discussed. 

PMID- 24033240
TI  - A review of the nurtured heart approach to parenting: evaluation of its
      theoretical and empirical foundations.
AB  - The Nurtured Heart Approach to parenting (NHA; Glasser & Easley, 2008) is
      summarized and evaluated in terms of its alignment with current theoretical
      perspectives and empirical evidence in family studies and developmental science.
      Originally conceived and promoted as a behavior management approach for parents
      of difficult children (i.e., with behavior disorders), NHA is increasingly
      offered as a valuable strategy for parents of any children, despite a lack of
      published empirical support. Parents using NHA are trained to minimize attention
      to undesired behaviors, provide positive attention and praise for compliance with
      rules, help children be successful by scaffolding and shaping desired behavior,
      and establish a set of clear rules and consequences. Many elements of the
      approach have strong support in the theoretical and empirical literature;
      however, some of the assumptions are more questionable, such as that negative
      child behavior can always be attributed to unintentional positive reinforcement
      by parents responding with negative attention. On balance, NHA appears to promote
      effective and validated parenting practices, but its effectiveness now needs to
      be tested empirically. 

PMID- 24033241
TI  - Father enrollment and participation in a parenting intervention: personal and
      contextual predictors.
AB  - Fathers are an important, though often underrepresented, population in family
      interventions. Notably, the inclusion of ethnic minority fathers is particularly
      scarce. An understanding of factors that promote and hinder father participation
      may suggest strategies by which to increase fathers' presence in studies designed
      to engage the family unit. The current research examined Mexican origin (MO)
      fathers' involvement in a family-focused intervention study. Participants
      included 495 fathers from eligible two-parent MO families with an adolescent
      child. Individual, familial, and culturally relevant predictors based on father,
      mother, and/or child report data were collected through pretest interviews and
      included in two separate logistic regression analyses that predicted the
      following: (1) father enrollment in the study and (2) father participation in the
      intervention. Results indicated that higher levels of maternal education and
      lower levels of economic stress and interparental conflict were associated with
      increased father enrollment in the study. Rates of father participation in the
      intervention were higher among families characterized by lower levels of
      interparental conflict, economic stress, and Spanish language use. Results
      highlight the relevancy of the familial and environmental context to MO fathers'
      research participation decisions. These findings as well as their implications
      for future research and practice are discussed. 

PMID- 24033242
TI  - Outcomes of an intensive couple relationship education program with fragile
      families.
AB  - Couple relationship education (CRE) has been proposed as one means to help
      fragile families stabilize their relationships. The current research is one of
      the first studies to look at the outcomes of a CRE program with fragile families
      in the areas of couple stability and marriage formation. Data were from the
      Family Formation Project, a federal and state funded program working with fragile
      family couples (n = 96) in a metropolitan area. A historical cohort control group
      quasi-experimental research design was used with a matched control group from the
      Fragile Family and Child Well-being Study. The intervention consisted of in-home
      education and support, group educational events, and social service referrals.
      Findings showed that couples had the same rate of couple stability as the control
      group but an increased rate of marriage. These findings suggest that CRE can help
      fragile families achieve marriage when that is their goal, but that some fragile
      families may need more than CRE to help them stabilize their relationship, or
      they may be better off separating. 

PMID- 24033243
TI  - Alliance and group cohesion in relationship education.
AB  - Relationship education programs have been shown as an effective way to increase
      relationship functioning. There is less known about how process factors, such as
      alliance with the leader or group dynamics, affect outcomes in these
      interventions. We examined group cohesion and alliance with the leader in a
      relationship education program tailored for individuals. Specifically, we
      examined whether participants' ratings (n = 126) of the group cohesion and
      alliance with the leader were associated with changes in relationship adjustment,
      relationship confidence, and communication quality from pre- to postintervention.
      The results demonstrated that participants' perceptions of the cohesion among the
      members in their relationship education group, but not the leader-participant
      alliance, made a significant contribution to the changes in participants'
      relationship functioning. These results suggest that the group dynamics among the
      members in the group are important ingredients in relationship education.
      Implications for relationship programs are provided. 

PMID- 24033244
TI  - Applying the creating lasting family connections marriage enhancement program to
      marriages affected by prison reentry.
AB  - Divorce proportions are currently high in the US and they are even higher among
      those who are incarcerated with substance abuse problems. Although much research
      has examined marital interventions, only two studies have examined marital
      interventions with prison populations. There is some empirical evidence that
      incarcerated couples benefit from traditional marital therapy (O'Farrell and Fals
      Stewart, 1999, Addictions: A comprehensive guidebook, New York, Oxford University
      Press). An adaptation of the evidence-based Creating Lasting Family Connections
      program was implemented with 144 married couples, where one spouse was
      incarcerated, in a southern state with particularly high divorce and
      incarceration proportions. Results suggested that married men exposed to the
      program had larger improvements in some relationship skills relative to a
      convenience sample of men not so exposed. Both husbands and wives exposed to the
      program exhibited similar and significant increases in relationship skills. The
      results were comparable to a Prevention and Relationship Enhancement Program
      adaptation for inmates. The implications of the findings for prevention
      practitioners are discussed. 

PMID- 24033245
TI  - Asian couples in negotiation: a mixed-method observational study of cultural
      variations across five Asian regions.
AB  - The purpose of this study was to explore variations in how contemporary couples
      from five different Asian regions negotiate disagreements. Video recordings of 50
      couples (10 each from Japan, Korea, Mainland China, Taiwan, and Hong Kong)
      discussing unresolved disagreements provided raw data for quantitative and
      qualitative analyses. First, teams of coders from each region used a common
      protocol to make quantitative ratings of content themes and interaction patterns
      for couples from their own region. An interregional panel of investigators then
      performed in-depth qualitative reviews for half of these cases, noting cultural
      differences not only in observed patterns of couple behavior but also in their
      own perceptions of these patterns. Both quantitative and qualitative analyses
      revealed clear regional differences on dimensions such as overt negativity,
      demand-withdraw interaction, and collaboration. The qualitative results also
      provided a richer, more nuanced view of other (e.g., gender-linked) conflict
      management patterns that the quantitative analyses did not capture.
      Inconsistencies between qualitative and quantitative data and between the
      qualitative observations of investigators from different regions were most
      pronounced for couples from Korea and Japan, whose conflict styles were subtler
      and less direct than those of couples from the other regions. 

PMID- 24033246
TI  - More than one way to be happy: a typology of marital happiness.
AB  - This study utilized observational and self-report data from 57 happily married
      couples to explore assumptions regarding marital happiness. Suggesting that
      happily married couples are not a homogeneous group, cluster analyses revealed
      the existence of three types of couples based on their observed behaviors in a
      problem-solving task: (1) mutually engaged couples (characterized by both
      spouses' higher negative and positive problem-solving); (2) mutually supportive
      couples (characterized by both spouses' higher positivity and support); and (3)
      wife compensation couples (characterized by high wife positivity). Although
      couples in all three clusters were equally happy with and committed to their
      marriages, these clusters were differentially associated with spouses'
      evaluations of their marriage. Spouses in the mutually supportive cluster
      reported greater intimacy and maintenance and less conflict and ambivalence,
      although this was more consistently the case in comparison to the wife
      compensation cluster, as opposed to the mutually engaged cluster. The
      implications of these typologies are discussed as they pertain to efforts on the
      part of both practitioners to promote marital happiness and repair marital
      relations when couples are faced with difficulties. 

PMID- 24033247
TI  - Linguistic indicators of wives' attachment security and communal orientation
      during military deployment.
AB  - Military deployment affects thousands of families each year, yet little is known
      about its impact on nondeployed spouses (NDSs) and romantic relationships. This
      report examines two factors-attachment security and a communal orientation with
      respect to the deployment-that may be crucial to successful dyadic adjustment by
      the NDS. Thirty-seven female NDSs reported on their relationship satisfaction
      before and during their partner's deployment, and 20 also did so 2 weeks
      following their partner's return. Participants provided a stream-of-consciousness
      speech sample regarding their relationship during the deployment; linguistic
      coding of sample transcripts provided measures of each participant's (a)
      narrative coherence, hypothesized to reflect attachment security with respect to
      their deployed spouse; and (b) frequency of first person plural pronoun use (we
      talk), hypothesized to reflect a communal orientation to coping. More frequent
      first person plural pronounuse-we-talk-was uniquely associated with higher
      relationship satisfaction during the deployment, and greater narrative coherence
      was uniquely associated with higher relationship satisfaction during
      postdeployment. Discussion centers on the value of relationship security and
      communal orientations in predicting how couples cope with deployment and other
      types of relationship stressors. 

PMID- 24033248
TI  - Wives' and husbands' cortisol reactivity to proximal and distal dimensions of
      couple conflict.
AB  - Poor marital quality has been linked repeatedly to spouses' health problems, with
      alterations to physiological stress response systems, such as the hypothalamic
      pituitary-adrenocortical (HPA) axis, as one putative mechanism. This study
      assessed wives' and husbands' HPA axis (i.e., cortisol) reactivity to marital
      criticism during laboratory-based conflict discussions, in the context of marital
      aggression experienced during the previous year. Ninety-five couples provided one
      saliva sample prior to-and three samples following-a triadic family conflict
      discussion involving their teenage child. Marital criticism during the conflict
      discussion was related to heightened HPA reactivity for husbands only. For wives,
      an interaction emerged between criticism during the conflict and previous-year
      marital aggression: only those wives who had experienced high levels of marital
      aggression demonstrated a positive association between criticism and cortisol
      output. Husbands thus appeared to be more physiologically reactive to the in-the
      moment critical behaviors, whereas wives' responses to proximal conflict were
      related to previous and perhaps more chronic experiences of marital aggression.
      These findings shed light on ways in which within-couple processes during family
      conflicts involving children contribute to individual physiological functioning,
      enhancing our understanding of the role of family relationships in physical
      health outcomes. 

PMID- 24033249
TI  - Sleep perception in non-insomniac healthy elderly: a 3-year longitudinal study.
AB  - OBJECTIVES: Older adults complain of sleep disturbances more often than younger
      adults do. It is not clear whether the age-related rise in sleep problems is
      related to aging itself or to health-related quality of life. The aim of this
      study was to explore the presence of self-reported sleep problems in healthy
      elderly individuals and to evaluate whether changes occurred over a 3-year follow
      up. METHODS: A total of 314 older community-dwelling volunteers, aged 71.6+/-1.0
      years old, were examined and followed for 3 years. All of the subjects completed
      questionnaires evaluating anxiety, depression, and sleepiness and the Pittsburgh
      Sleep Quality Index (PSQI) at the first and second evaluations. On the basis of
      the PSQI items, the subjects were classified as good or bad sleepers and as
      short, normal, or long sleepers. RESULTS: At baseline, 53% of the subjects
      reported good sleep, with 61% reporting a sleep duration of approximately 7 hr.
      The total sleep time and the numbers of short, normal, and long sleepers were
      similar at baseline and at 3 years later. Over time, there was a slight increase
      (p<0.001) in bad sleepers (53%) and a rise in the occasional hypnotic intake
      (p<0.001). Considering individual variation, the majority of subjects remained
      stable at follow-up for sleep duration (65%), sleep quality (75%), and medication
      (83%). CONCLUSIONS: In a healthy older population, the majority of the subjects
      did not report bad and short sleep at baseline and did not have significant
      changes in self-perceived sleep 3 years later. These findings suggest that the
      reported sleep disturbances described in the elderly are more dependent on
      physical, environmental, and health factors rather than on age-dependent sleep
      changes. CLINICAL TRIAL REGISTRATION: NCT 00759304 and NCT 00766584.

PMID- 24033250
TI  - A randomized, open-label, phase I/II trial to investigate the maximum tolerated
      dose of the Polo-like kinase inhibitor BI 2536 in elderly patients with
      refractory/relapsed acute myeloid leukaemia.
AB  - Polo-like kinases (Plks) play an important role in cell cycle checkpoint controls
      and are over-expressed in acute myeloid leukaemia (AML). BI 2536, a novel Plk
      inhibitor, induces mitotic arrest and apoptosis. In this phase I/II trial of BI
      2536 in 68 elderly patients with relapsed/refractory AML, three schedules were
      investigated (day 1, days 1-3, and days 1 + 8). Maximum tolerated dose was 350
      and 200 mg in the day 1 and days 1 + 8 schedules, respectively. The day 1-3
      schedule appeared equivalent to the day 1 schedule and was discontinued early. BI
      2536 exhibited multi-compartmental pharmacokinetic behaviour. The majority of
      patients showed an increase of bone marrow cells in G2/M with a characteristic
      pattern of mitotic catastrophe. The overall response rate in the day 1 and day 1
      + 8 schedules was 9% (5/54) with 2 complete and 3 partial responses. The majority
      of drug-related adverse events grade >=3 were haematological. Taken together, Plk
      inhibition induced cell cycle arrest in AML blasts in vivo and BI 2536
      monotherapy showed modest clinical activity in this poor prognosis patient group.

PMID- 24033251
TI  - Lower risk of atopic dermatitis among infants born extremely preterm compared
      with higher gestational age.
AB  - BACKGROUND: It is not yet known whether the risk of developing atopic dermatitis
      (AD) is influenced by preterm birth. Moreover, AD risk has not been assessed in a
      large sample of extremely preterm infants (< 29 weeks' gestation). OBJECTIVES: To
      determine whether the risk of AD is influenced by preterm birth. METHODS: We
      investigated the relationship between gestational age (GA) and AD using data from
      two independent population-based cohorts, including a total of 2329 preterm
      infants, of whom 479 were born extremely preterm. RESULTS: There was a lower
      percentage of children with AD in the extremely preterm group compared with those
      born at a greater GA (Epipage cohort, 2-year outcome: 13.3% for 24-28 weeks,
      17.6% for 29-32 weeks, 21.8% for 33-34 weeks, P = 0.02; LIFT cohort, 5-year
      outcome: 11% for 24-28 weeks, 21.5% for 29-32 weeks, 19.6% for 33-34 weeks, P =
      0.11). After adjusting for confounding variables, a lower GA (< 29 weeks) was
      significantly associated with decreased risk of AD in the Epipage cohort
      [adjusted odds ratio (aOR) 0.57, 95% confidence interval (CI) 0.37-0.87; P =
      0.009] and the LIFT cohort (aOR 0.41, 95% CI 0.18-0.90; P = 0.03). CONCLUSIONS:
      Very low GA (< 29 weeks) was associated with a lower risk of AD compared with
      higher GA (29-34 weeks) and full-term birth.

PMID- 24033252
TI  - Multiple step growth of single crystalline rutile nanorods with the assistance of
      self-assembled monolayer for dye sensitized solar cells.
AB  - A novel multiple step growth (MSG) process has been developed to synthesize
      rutile nanorods (NRs) on fluorine-doped tin oxide (FTO) glass with the assistance
      of a self-assembled monolayer (SAM) aiming to increase the internal surface area
      of the 1D materials for dye sensitized solar cell (DSSC) applications. The
      experimental result reveals that the SAM layer can be selectively decomposed at
      the tip of the nanorod, namely the rutile (001) surface, due to the anisotropic
      photocatalytic property of the rutile. The remaining SAM layer on the side-wall
      of the NRs remains intact and serves as water repellent which prevents the radial
      growth of the NRs during the next step hydrothermal synthesis; therefore, the
      spacing between the NRs and the porosity of the NR array can be retained after
      additional growth cycles. On the other hand, introduction of a middle layer
      formed via TiCl4 solution treatment before the next growth cycle is found to be
      an effective way to control the diameters of the newly grown NRs. The performance
      of DSSC made from the rutile NRs grown using the MSG technique has been examined,
      and it is significantly affected by the internal surfaces of the NRs.
      Furthermore, the MSG combined with NR etching treatment by acid at low
      temperature (150  degrees C) leads to a significant enhancement in the solar cell
      performance. The gigantic wettability difference of the NRs before and after the
      SAM treatment as well as the MSG method could be adapted to prepare
      superhydrophobic and superhydrophilic nanostructured patterns for other
      applications. 

PMID- 24033253
TI  - Emerging drugs for treatment of anemia of chronic kidney disease.
AB  - INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) prevent transfusions among
      anemic patients with chronic kidney disease (CKD). Clinical trials, meta
      analyses, and guidelines identify arterial and venous thromboembolism as well as
      myocardial event risks with the traditional ESAs, erythropoietin (EPO), and
      darbepoietin. Side effects of anemia treatment, considering frequency and dosage
      of treatment as well as targeted hemoglobin levels when utilizing ESAs, greatly
      impact overall well-being and the quality of life. There is a need for less
      frequent but equally effective ESAs in this setting. AREAS COVERED: The three
      generations of ESAs used in CKD-associated anemia are described. Cost
      effectiveness of the utilization of these therapies, in addition to emerging
      therapies, is also presented. The few clinical and controlled trials only
      highlight the need for clarity in molecular biology surrounding the components
      that control EPO levels and utilization. EXPERT OPINION: Anemia associated with
      CKD is an important area for development of newer therapies which are potentially
      safer and more convenient to administer.

PMID- 24033254
TI  - Nitrogen removal from wastewater by coupling anammox and methane-dependent
      denitrification in a membrane biofilm reactor.
AB  - This work demonstrates, for the first time, the feasibility of nitrogen removal
      by using the synergy of anammox and denitrifying anaerobic methane oxidation
      (DAMO) microorganisms in a membrane biofilm reactor (MBfR). The reactor was fed
      with synthetic wastewater containing nitrate and ammonium. Methane was delivered
      from the interior of hollow fibres in the MBfR to the biofilm that grew on the
      fiber's outer wall. After 24 months of operation, the system achieved a nitrate
      and an ammonium removal rate of about 190 mgN L(-1) d(-1) (or 86 mgN m(-2) d(-1),
      with m(2) referring to biofilm surface area) and 60 mgN L(-1) d(-1) (27 mgN m(-2)
      d(-1)), respectively. No nitrite accumulation was observed. Fluorescence in situ
      hybridization (FISH) analysis indicated that DAMO bacteria (20-30%), DAMO archaea
      (20-30%) and anammox bacteria (20-30%) jointly dominated the microbial community.
      Based on the known metabolism of these microorganisms, mass balance, and isotope
      studies, we hypothesize that DAMO archaea converted nitrate, both externally fed
      and produced by anammox, to nitrite, with methane as the electron donor. Anammox
      and DAMO bacteria jointly removed the nitrite produced, with ammonium and methane
      as the electron donor, respectively. The process could potentially be used for
      anaerobic nitrogen removal from wastewater streams containing ammonium and
      nitrate/nitrite. 

PMID- 24033256
TI  - Open Stomata 1 (OST1) is limiting in abscisic acid responses of Arabidopsis guard
      cells.
AB  - Open Stomata 1 (OST1) (SnRK2.6 or SRK2E), a serine/threonine protein kinase, is a
      positive regulator in abscisic acid (ABA)-mediated stomatal response, but OST1
      regulation of K(+) and Ca(2+) currents has not been studied directly in guard
      cells and it is unknown whether OST1 activity is limiting in ABA-mediated
      stomatal responses. We employed loss-of-function and gain-of-function approaches
      to study native ABA responses of Arabidopsis guard cells. We performed stomatal
      aperture bioassays, patch clamp analyses and reactive oxygen species (ROS)
      measurements. ABA inhibition of inward K(+) channels and light-induced stomatal
      opening are reduced in ost1 mutants while transgenic plants overexpressing OST1
      show ABA hypersensitivity in these responses. ost1 mutants are insensitive to ABA
      induced stomatal closure, regulation of slow anion currents, Ca(2+) -permeable
      channel activation and ROS production while OST1 overexpressing lines are
      hypersensitive for these responses, resulting in accelerated stomatal closure in
      response to ABA. Overexpression of OST1 in planta in the absence of ABA
      application does not affect basal apertures or ion currents. Moreover, we
      demonstrate the physical interaction of OST1 with the inward K(+) channel KAT1,
      the anion channel SLAC1, and the NADPH oxidases AtrbohD and AtrbohF. Our findings
      support OST1 as a critical limiting component in ABA regulation of stomatal
      apertures, ion channels and NADPH oxidases in Arabidopsis guard cells. 

PMID- 24033257
TI  - General approach for engineering small-molecule-binding DNA split aptamers.
AB  - Here we report a general method for engineering three-way junction DNA aptamers
      into split aptamers. Split aptamers show significant potential for use as
      recognition elements in biosensing applications, but reliable methods for
      generating these sequences are currently lacking. We hypothesize that the three
      way junction is a "privileged architecture" for the elaboration of aptamers into
      split aptamers, as it provides two potential splitting sites that are distal from
      the target binding pocket. We propose a general method for split aptamer
      engineering that involves removing one loop region, then systematically modifying
      the number of base pairs in the remaining stem regions in order to achieve
      selective assembly only in the presence of the target small molecule. We screen
      putative split aptamer sequence pairs using split aptamer proximity ligation
      (StAPL) technology developed by our laboratory, but we validate that the results
      obtained using StAPL translate directly to systems in which the aptamer fragments
      are assembling noncovalently. We introduce four new split aptamer sequences,
      which triples the number of small-molecule-binding DNA split aptamers reported to
      date, and the methods described herein provide a reliable route for the
      engineering of additional split aptamers, dramatically advancing the potential
      substrate scope of DNA assembly based biosensors. 

PMID- 24033259
TI  - Does parental involvement matter for student achievement and mental health in
      high school?
AB  - Parental involvement in education remains important for facilitating positive
      youth development. This study conceptualized parental involvement as a
      multidimensional construct-including school-based involvement, home-based
      involvement, and academic socialization-and examined the effects of different
      types of parental involvement in 10th grade on student achievement and depression
      in 11th grade (approximately ages 15-17 years). In addition, this study tested
      whether parental involvement influenced adolescent outcomes by increasing their
      academic engagement in school. A total of 1,056 adolescents participated in the
      study (51% males; 53% European American, 40% African American, and 7% other).
      Parental involvement was found to improve academic and emotional functioning
      among adolescents. In addition, parental involvement predicted adolescent
      academic success and mental health both directly and indirectly through
      behavioral and emotional engagement.

PMID- 24033258
TI  - Juveniles and migrants as drivers for seasonal epizootics of avian influenza
      virus.
AB  - Similar to other infectious diseases, the prevalence of low pathogenic avian
      influenza viruses (LPAIV) has been seen to exhibit marked seasonal variation.
      However, mechanisms driving this variation in wild birds have yet to be tested.
      We investigated the validity of three previously suggested drivers for the
      seasonal dynamics in LPAIV infections in wild birds: (i) host density, (ii)
      immunologically naive young and (iii) increased susceptibility in migrants. To
      address these questions, we sampled a key LPAIV host species, the mallard Anas
      platyrhynchos, on a small spatial scale, comprehensively throughout a complete
      annual cycle, measuring both current and past infection (i.e. viral and
      seroprevalence, respectively). We demonstrate a minor peak in LPAIV prevalence in
      summer, a dominant peak in autumn, during which half of the sampled population
      was infected, and no infections in spring. Seroprevalence of antibodies to a
      conserved gene segment of avian influenza virus (AIV) peaked in winter and again
      in spring. The summer peak of LPAIV prevalence coincided with the entrance of
      unfledged naive young in the population. Moreover, juveniles were more likely to
      be infected, shed higher quantities of virus and were less likely to have
      detectable antibodies to AIV than adult birds. The arrival of migratory birds, as
      identified by stable hydrogen isotope analysis, appeared to drive the autumn peak
      in LPAIV infection, with both temporal coincidence and higher infection
      prevalence in migrants. Remarkably, seroprevalence in migrants was substantially
      lower than viral prevalence throughout autumn migration, further indicating that
      each wave of migrants amplified local AIV circulation. Finally, while host
      abundance increased throughout autumn, it peaked in winter, showing no direct
      correspondence with either of the LPAIV infection peaks. At an epidemiologically
      relevant spatial scale, we provide strong evidence for the role of migratory
      birds as key drivers for seasonal epizootics of LPAIV, regardless of their role
      as vectors of these viruses. This study exemplifies the importance of
      understanding host demography and migratory behaviour when examining seasonal
      drivers of infection in wildlife populations. 

PMID- 24033260
TI  - Immobilized organic photosensitizers with versatile reactivity for various
      visible-light applications.
AB  - Various photosensitizers were grafted by conventional peptide coupling methods to
      functionalized silica with several macroscopic shapes (powders, films) or
      embedded in highly transparent and microporous silica xerogel monoliths. Owing to
      the transparency and free-standing shape of the monoliths, the transient species
      arising from irradiation of the PSs could be analyzed and were not strikingly
      different from those observed in solutions. The observed reactivity for either
      liquid-solid (alpha-terpinene oxygenation vs dehydrogenation) or gas-solid
      (dimethylsulfide, DMS, solvent-free oxidation) reactions was consistent with the
      properties of the excited states of the PSs under consideration. Immobilized
      anthraquinone-derived materials preferentially react in both cases by electron
      transfer from the substrate to the triplet state of the sensitizer, in spite of
      an efficient singlet oxygen production. The recently developed 9,14
      dicyanobenzo[b]triphenylene-3-carboxylic acid, DBTP-COOH, efficiently reacts via
      energy transfer to yield singlet oxygen from its triplet state. It was shown to
      perform better than 9,10-dicyanoanthracene and rose bengal for DMS oxidation and
      alpha-terpinene photooxygenation to ascaridole, respectively. Thus, by a proper
      choice of the organic immobilized photocatalyst, it is possible to develop
      efficient and reusable materials, activated under visible light, for various
      applications and to tune the reaction pathway, opening the way to green oxidation
      processes. 

PMID- 24033261
TI  - Efficiently identifying significant associations in genome-wide association
      studies.
AB  - Over the past several years, genome-wide association studies (GWAS) have
      implicated hundreds of genes in common disease. More recently, the GWAS approach
      has been utilized to identify regions of the genome that harbor variation
      affecting gene expression or expression quantitative trait loci (eQTLs). Unlike
      GWAS applied to clinical traits, where only a handful of phenotypes are analyzed
      per study, in eQTL studies, tens of thousands of gene expression levels are
      measured, and the GWAS approach is applied to each gene expression level. This
      leads to computing billions of statistical tests and requires substantial
      computational resources, particularly when applying novel statistical methods
      such as mixed models. We introduce a novel two-stage testing procedure that
      identifies all of the significant associations more efficiently than testing all
      the single nucleotide polymorphisms (SNPs). In the first stage, a small number of
      informative SNPs, or proxies, across the genome are tested. Based on their
      observed associations, our approach locates the regions that may contain
      significant SNPs and only tests additional SNPs from those regions. We show
      through simulations and analysis of real GWAS datasets that the proposed two
      stage procedure increases the computational speed by a factor of 10.
      Additionally, efficient implementation of our software increases the
      computational speed relative to the state-of-the-art testing approaches by a
      factor of 75.

PMID- 24033262
TI  - Reconciliation revisited: handling multiple optima when reconciling with
      duplication, transfer, and loss.
AB  - Phylogenetic tree reconciliation is a powerful approach for inferring
      evolutionary events like gene duplication, horizontal gene transfer, and gene
      loss, which are fundamental to our understanding of molecular evolution. While
      duplication-loss (DL) reconciliation leads to a unique maximum-parsimony
      solution, duplication-transfer-loss (DTL) reconciliation yields a multitude of
      optimal solutions, making it difficult to infer the true evolutionary history of
      the gene family. This problem is further exacerbated by the fact that different
      event cost assignments yield different sets of optimal reconciliations. Here, we
      present an effective, efficient, and scalable method for dealing with these
      fundamental problems in DTL reconciliation. Our approach works by sampling the
      space of optimal reconciliations uniformly at random and aggregating the results.
      We show that even gene trees with only a few dozen genes often have millions of
      optimal reconciliations and present an algorithm to efficiently sample the space
      of optimal reconciliations uniformly at random in O(mn(2)) time per sample, where
      m and n denote the number of genes and species, respectively. We use these
      samples to understand how different optimal reconciliations vary in their node
      mappings and event assignments and to investigate the impact of varying event
      costs. We apply our method to a biological dataset of approximately 4700 gene
      trees from 100 taxa and observe that 93% of event assignments and 73% of mappings
      remain consistent across different multiple optima. Our analysis represents the
      first systematic investigation of the space of optimal DTL reconciliations and
      has many important implications for the study of gene family evolution.

PMID- 24033263
TI  - Adherence and assured administration of medications in bipolar patients.
AB  - Adherence to treatment is a major determinant of outcome in bipolar disorder.
      Poor insight, attitudes towards treatment, and poor understanding of medications
      and the illness can all lead to reduced adherence. Nonadherence and partial
      adherence both also appear to play a significant role in relapse and recurrence.
      Clinicians can address the problem of poor adherence by ensuring medication
      administration. Assured administration can be accomplished with long-acting
      atypical antipsychotic medications. Case series and naturalistic trials utilizing
      first generation antipsychotics suggest that depot antipsychotics are effective
      in reducing relapse in bipolar illness. Controlled studies with second generation
      agents confirm this impression. Depot antipsychotics, including long-acting first
      and second-generation agents, can be important adjuncts in the long-term
      management of bipolar illness. 

PMID- 24033264
TI  - New insights into the diagnosis and chemotheraphy for visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) is a severe form of leishmaniasis - a disease caused
      by protozoan parasites and transmitted by the bite of certain species of sand
      fly. In VL, parasites migrate to the vital organs and bone marrow, destroying
      white and red blood cells. VL has been called the parasitic version of HIV/AIDs
      (Human immunodeficiency virus infection / acquired immunodeficiency syndrome), as
      it attacks the immune system. The most common form of the disease is cutaneous
      leishmaniasis, which causes skin lesions and often leaves the infected individual
      permanently disfigured. Even though the disease is treatable, current treatments
      are difficult to administer, too expensive, or toxic for extensive use in
      developing nations. Furthermore, resistance to treatment is an increasing
      problem, particularly in India. 90% of people with VL die if the infection is
      left untreated, and death can come within 2 years, significantly faster than
      AIDS. The search for new drugs continues, with new chemical and natural
      compounds. Many potential drug targets have been identified in biochemical and
      molecular studies, and some have been validated. Attempts to exploit these
      targets are in progress. This article reviews the epidemiology, clinical
      features, control Strategies, diagnosis and current treatment about visceral
      leishmaniasis. 

PMID- 24033265
TI  - Absence of the right wing of the ilium generated a compensatory scoliosis in
      rhesus monkey in captivity: diagnostic imaging and its alteration on the SEPNT.
AB  - BACKGROUND: Congenital scoliosis (CS) is defined as lateral curvatures of the
      spine provoked by the anomalous development of the vertebral bodies. It is
      associated with neuromuscular anomalies, which can be genetic, caused by the
      compensation of discrepancies in the length of the extremities or intrarachidian
      anomalies. METHODS: This study was carried out in 2-year-old female, showed
      alterations in the gait, mainly in the hind limbs, a clumsy gait and a slight
      claudication in the right hindlimb. To perform the imaging study were: X-Ray
      projections and Computerized Axial Tomography, neurophysiological evaluation was
      performed by means somatosensory-evoked potentials of the tibial nerve (SEPTN).
      RESULTS: The results showed an enlargement of the latencies from the L5 to the
      cortex, mainly in the left afference, correlated with the imaging studies.
      CONCLUSIONS: There is no doubt that the concurrent use of different diagnostic
      tools complements knowledge regarding the physiopathogenesis of these
      osteopathologies.

PMID- 24033267
TI  - The plant extract of Pao pereira potentiates carboplatin effects against ovarian
      cancer.
AB  - CONTEXT: Herbal preparation of Pao pereira [Geissospermum vellosii Allem
      (Apocynaceae)] has long been used by oncologic patients and Integrative Medicine
      practitioners in South America. However, its anticancer activities have not been
      systematically studied. OBJECTIVE: To investigate the anticancer effects of beta
      carboline alkaloids-enriched extract from Pao pereira (Pao), either alone or in
      combination with carboplatin, in preclinical ovarian cancer models. MATERIALS AND
      METHODS: Cytotoxicity of Pao (0-800 ug/ml) against different ovarian cancer cell
      lines and an immortalized epithelial cell line was detected by flow cytometry,
      MTT assay and colony formation in soft agar. Combination of Pao and carboplatin,
      a primary chemotherapeutic drug for ovarian cancer, was evaluated using Chou
      Talalay's methods. Mice bearing intraperitoneally spread ovarian cancer were
      treated with 20 or 50 mg/kg/day Pao by i.p. injection. Carboplatin at 15
      mg/kg/week i.p. was compared and combined to Pao treatments. RESULTS: Pao
      selectively inhibited ovarian cancer cell growth with IC50 values of 180-235
      ug/ml, compared to 537 ug/ml in normal cells. Pao induced apoptosis dose- and
      time-dependently and completely inhibited colony formation of tumor cells in soft
      agar at 400 ug/ml. Pao greatly enhanced carboplatin cytotoxicity, with dose
      reduction (DRIs) for carboplatin at 1.2-10 fold. In vivo, Pao alone suppressed
      tumor growth by 79% and decreased volume of ascites by 55%. When Pao was combined
      with carboplatin, tumor inhibition reached 97% and ascites was completely
      eradicated. DISCUSSION AND CONCLUSION: Pao possess potent antitumor activity and
      could enhance carboplatin effect, and therefore holds therapeutic potential in
      the treatment of ovarian cancer.

PMID- 24033266
TI  - A systematic approach to assessing the clinical significance of genetic variants.
AB  - Molecular genetic testing informs diagnosis, prognosis, and risk assessment for
      patients and their family members. Recent advances in low-cost, high-throughput
      DNA sequencing and computing technologies have enabled the rapid expansion of
      genetic test content, resulting in dramatically increased numbers of DNA variants
      identified per test. To address this challenge, our laboratory has developed a
      systematic approach to thorough and efficient assessments of variants for
      pathogenicity determination. We first search for existing data in publications
      and databases including internal, collaborative and public resources. We then
      perform full evidence-based assessments through statistical analyses of
      observations in the general population and disease cohorts, evaluation of
      experimental data from in vivo or in vitro studies, and computational predictions
      of potential impacts of each variant. Finally, we weigh all evidence to reach an
      overall conclusion on the potential for each variant to be disease causing. In
      this report, we highlight the principles of variant assessment, address the
      caveats and pitfalls, and provide examples to illustrate the process. By sharing
      our experience and providing a framework for variant assessment, including access
      to a freely available customizable tool, we hope to help move towards
      standardized and consistent approaches to variant assessment. 

PMID- 24033268
TI  - Adult Attachment Ratings (AAR): an item response theory analysis.
AB  - The Adult Attachment Ratings (AAR) include 3 scales for anxious, ambivalent
      attachment (excessive dependency, interpersonal ambivalence, and compulsive care
      giving), 3 for avoidant attachment (rigid self-control, defensive separation, and
      emotional detachment), and 1 for secure attachment. The scales include items
      (ranging from 6-16 in their original form) scored by raters using a 3-point
      format (0 = absent, 1 = present, and 2 = strongly present) and summed to produce
      a total score. Item response theory (IRT) analyses were conducted with data from
      414 participants recruited from psychiatric outpatient, medical, and community
      settings to identify the most informative items from each scale. The IRT results
      allowed us to shorten the scales to 5-item versions that are more precise and
      easier to rate because of their brevity. In general, the effective range of
      measurement for the scales was 0 to +2 SDs for each of the attachment constructs;
      that is, from average to high levels of attachment problems. Evidence for
      convergent and discriminant validity of the scales was investigated by comparing
      them with the Experiences of Close Relationships-Revised (ECR-R) scale and the
      Kobak Attachment Q-sort. The best consensus among self-reports on the ECR-R,
      informant ratings on the ECR-R, and expert judgments on the Q-sort and the AAR
      emerged for anxious, ambivalent attachment. Given the good psychometric
      characteristics of the scale for secure attachment, however, this measure alone
      might provide a simple alternative to more elaborate procedures for some
      measurement purposes. Conversion tables are provided for the 7 scales to
      facilitate transformation from raw scores to IRT-calibrated (theta) scores. 

PMID- 24033269
TI  - V-type allosteric inhibition is described by a shift in the rate-determining step
      for alpha-isopropylmalate synthase from Mycobacterium tuberculosis.
AB  - The kinetic parameters affected by allosteric mechanisms contain collections of
      rate constants that vary based on differences in the relative rates of individual
      steps in the reaction. Thus, it may not be useful to compare enzymes with similar
      allosteric mechanisms unless the point of regulation has been identified. Rapid
      reaction kinetics and kinetic isotope effects provide a detailed description of V
      type feedback allosteric inhibition in alpha-isopropylmalate synthase from
      Mycobacterium tuberculosis, an evolutionarily conserved model allosteric system.
      Results are consistent with a shift in the rate-determining step from product
      release to the hydrolytic step in catalysis in the presence of the effector. 

PMID- 24033271
TI  - Two novel HLA class II alleles, DRB1*11:131 and DQB1*05:01:05, identified by
      sequence-based typing.
AB  - Two novel class II human leukocyte antigen alleles HLA-DRB1*11:131 and HLA
      DQB1*05:01:05 are described. 

PMID- 24033270
TI  - Noninvasive fluorescence resonance energy transfer imaging of in vivo premature
      drug release from polymeric nanoparticles.
AB  - Understanding in vivo drug release kinetics is critical for the development of
      nanoparticle-based delivery systems. In this study, we developed a fluorescence
      resonance energy transfer (FRET) imaging approach to noninvasively monitor in
      vitro and in vivo cargo release from polymeric nanoparticles. The FRET donor dye
      (DiO or DiD) and acceptor dye (DiI or DiR) were individually encapsulated into
      poly(ethylene oxide)-b-polystyrene (PEO-PS) nanoparticles. When DiO (donor)
      nanoparticles and DiI (acceptor) nanoparticles were coincubated with cancer cells
      for 2 h, increased FRET signals were observed from cell membranes, suggesting
      rapid release of DiO and DiI to cell membranes. Similarly, increased FRET ratios
      were detected in nude mice after intravenous coadministration of DiD (donor)
      nanoparticles and DiR (acceptor) nanoparticles. In contrast, another group of
      nude mice i.v. administrated with DiD/DiR coloaded nanoparticles showed decreased
      FRET ratios. Based on the difference in FRET ratios between the two groups, in
      vivo DiD/DiR release half-life from PEO-PS nanoparticles was determined to be 9.2
      min. In addition, it was observed that the presence of cell membranes facilitated
      burst release of lipophilic cargos while incorporation of oleic acid-coated iron
      oxide into PEO-PS nanoparticles slowed the release of DiD/DiR to cell membranes.
      The developed in vitro and in vivo FRET imaging techniques can be used to
      screening stable nanoformulations for lipophilic drug delivery. 

PMID- 24033272
TI  - Treatment of elderly patients with acute lymphoblastic leukaemia using a
      paediatric-based protocol.
AB  - All newly diagnosed patients aged 60-79 years with acute lymphoblastic leukaemia
      (ALL) receiving induction chemotherapy with a modified paediatric-based regimen
      over a 7-year period were retrospectively analysed (n = 51, median age 65 years).
      The treatment regimen consisted of induction, central nervous system prophylaxis,
      seven cycles of intensification and 24 cycles of maintenance. BCR-ABL1 negative
      patients received weekly asparaginase during intensification, while BCR-ABL1+
      patients received daily imatinib. Post-remission therapy was given in an
      outpatient setting. The complete response rate was 75%, with an induction
      mortality of 20%; 6% of patients had resistant disease. 37% of patients who
      achieved a complete remission relapsed. The estimated 5-year overall survival was
      40% for BCR-ABL1 negative and 47% for BCR-ABL1+ patients (P = not significant);
      the 5-year disease-free survival was 57% and 39%, respectively (P = NS). The post
      induction phase was generally well tolerated, with 81% able to complete the
      intensification phase and proceed to maintenance. In conclusion, administration
      of this modified paediatric-based protocol is feasible and active for elderly
      patients with ALL. Survival is superior to most previously reported series in
      this age group, but remains worse compared to younger patients. Further
      improvement of the toxicity profile, particularly during induction, is required
      to improve outcomes.

PMID- 24033273
TI  - A post-DSM-III wake-up call to European psychiatry.

PMID- 24033274
TI  - Aspects of ion hydration. Adiabatic compressibility compared to the dielectric
      properties of aqueous electrolyte solutions.
AB  - Adiabatic compressibility data and principal dielectric relaxation times for
      aqueous solutions of 1:1 and 2:1 valent electrolytes are evaluated to yield their
      relative molal shifts Bkappa and Bd, respectively, at low solute concentration.
      Cationic (Bx(+)) and anionic (Bx(-)) contributions to these quantities are
      calculated and compared to one another. For some ions also the correspondent
      relative molal shifts (Bm(+/-)) in the intramolecular proton magnetic relaxation
      rates are considered. Clear correlations between Bkappa(+/-) and Bd(+/-) values
      are found for most series of ions. Within the series of halide ions, for example,
      Bkappa(-) increases, whereas Bd(-) decreases with anion radius. For large
      hydrophobic cations the opposite is true; that is, Bkappa(+) increases and Bd(+)
      decreases with molar volume of ion. In general, the magnitudes |Bk(+/-)| in the
      changes of the compressibility coefficient are smaller than in the shifts of the
      dielectric relaxation time. The situation is more complicated with dielectrically
      saturated small ions. Since the apparently irrotationally bound water molecules
      around such ions do not contribute to the dielectric spectra by reorientation,
      comparison of compressibility changes with changes in the proton magnetic
      relaxation rate rather than in the dielectric relaxation time is more
      appropriate. Some composite ions, such as BF4(-), show special features which
      can, however, be explained by a nonspherical charge distribution at the ion
      surface.

PMID- 24033275
TI  - Measurement equivalence of the autism symptom phenotype in children and youth.
AB  - BACKGROUND: The Autism Diagnostic Interview-Revised (ADI-R) is a gold standard
      assessment of Autism Spectrum Disorder (ASD) symptoms and behaviours. A key
      underlying assumption of studies using the ADI-R is that it measures the same
      phenotypic constructs across different populations (i.e., males/females,
      younger/older, verbal/nonverbal). The objectives of this study were to evaluate
      alternative measurement models for the autism symptom phenotype based on the ADI
      R algorithm items and to examine the measurement equivalence of the most
      parsimonious and best fitting model across subgroups of interest. METHODS: Data
      came from the Autism Genome Project consortium and consisted of 3,628 children
      aged 4-18 years (84.2% boys and 75% verbal). Twenty-eight algorithm items
      applicable to both verbal and nonverbal participants were used in the analysis.
      Measurement equivalence of the autism phenotype was examined using categorical
      confirmatory factor analysis. RESULTS: A second-order model resembling the
      proposed DSM-5 two-factor structure of the phenotype showed good overall fit, but
      not for all the subgroups. The autism symptom phenotype was best indexed by the
      first-order, six-factor measurement model proposed by Liu et al. (2011). This
      model was well fitting and measurement equivalent across subgroups of
      participants (age, verbal ability and sex). CONCLUSIONS: The autism symptom
      phenotype is adequately characterized by a six-factor measurement model; this
      model appears to be measurement equivalent across subgroups of children and youth
      with ASD that differ in age, sex and verbal ability. The two-factor model
      provides equally good fit for the sample as a whole, but comparison of these two
      dimensions between subgroups that might differ in terms of age, sex or verbal
      ability is challenged by lack of measurement equivalence.

PMID- 24033277
TI  - Opportunities to build groundwater resilience in the semi-arid tropics.
AB  - Agricultural water management (AWM) is the adaptation strategy for increasing
      agricultural production through enhancing water resources availability while
      maintaining ecosystem services. This study characterizes groundwater hydrology in
      the Kothapally agricultural watershed, in hard rock Deccan plateau area in India
      and assesses the impact of AWM interventions on groundwater recharge using a
      calibrated and validated hydrological model, SWAT, in combination with observed
      water table data in 62 geo-referenced open wells. Kothapally receives, on
      average, 750 mm rainfall (nearly 90% of annual rainfall) during the monsoon
      season (June to October). Water balance showed that 72% of total rainfall was
      converted as evapotranspiration (ET), 16% was stored in aquifer, and 8% exported
      as runoff from the watershed boundary with AWM interventions. Nearly 60% of the
      runoff harvested by AWM interventions recharged shallow aquifers and rest of the
      40% increased ET. Water harvesting structures (WHS) contributed 2.5 m additional
      head in open wells, whereas hydraulic head under natural condition was 3.5 m,
      resulting in total 6 m rise in water table during the monsoon. At the field
      scale, WHSs recharged open wells at a 200 to 400 m spatial scale. 

PMID- 24033276
TI  - Flow-mediated stem cell labeling with superparamagnetic iron oxide nanoparticle
      clusters.
AB  - This study presents a strategy to enhance the uptake of superparamagnetic iron
      oxide nanoparticle (SPIO) clusters by manipulating the cellular mechanical
      environment. Specifically, stem cells exposed to an orbital flow ingested almost
      a 2-fold greater amount of SPIO clusters than those cultured statically.
      Improvements in magnetic resonance (MR) contrast were subsequently achieved for
      labeled cells in collagen gels and a mouse model. Overall, this strategy will
      serve to improve the efficiency of cell tracking and therapies. 

PMID- 24033278
TI  - Anaerobic oxidation of ethene coupled to sulfate reduction in microcosms and
      enrichment cultures.
AB  - Ethene is considered recalcitrant under anaerobic conditions, but biological
      reduction to ethane and oxidation to CO2 have been reported; however, little is
      known about these processes or the organisms carrying them out. In this report we
      describe sulfate dependent ethene consumption in microcosms prepared with
      sediments from a freshwater canal. A first dose of 0.6 mmol/L ethene was consumed
      within 77 days, and a second dose was largely consumed twelve days later.
      Material from this microcosm was transferred into growth medium with ethene as
      the only electron donor (except for trace amounts of vitamins) and sulfate as the
      electron acceptor. Four doses of ethene were consumed at increasing rates, and
      the cultures have been transferred at least eight times in this medium.
      Conversion of [(14)C]ethene primarily to (14)CO2 was demonstrated in fifth and
      sixth generation cultures, as well as production of sulfide in other cultures,
      confirming the ethene/sulfate couple. Ovoid cells 1-2 MUm in diameter were found
      in cultures containing ethene and sulfate, and quantitative PCR showed large
      increases in bacterial 16S rRNA gene copy number. Over half of a 16S rRNA gene
      clone library from a sixth-generation culture was a phylotype with a sequence ca.
      90% identical with a clade of Deltaproteobacteria that includes Desulfovirga
      adipica and several Syntrophobacter spp. These studies have solidified the
      concept that deficits in mass balances for chloroethene fate in sulfate reducing
      zones of contaminated groundwater sites may be due to ethene oxidation, and
      suggest a unique phylotype is involved in this process. 

PMID- 24033279
TI  - Can tissue dielectric constant measurement aid in differentiating lymphoedema
      from lipoedema in women with swollen legs?
AB  - BACKGROUND: Distinguishing lymphoedema from lipoedema in women with swollen legs
      can be difficult. Local tissue water content can be quantified using tissue
      dielectric constant (TDC) measurements. OBJECTIVES: To examine whether TDC
      measurements can differentiate untreated lower extremity lymphoedema from
      lipoedema, and to test interobserver agreement. METHODS: Thirty-nine women
      participated in the study; 10 patients with lipoedema (LipP), nine patients with
      untreated lymphoedema (U-LP), 10 patients with lymphoedema treated with
      compression bandaging for >= 4 weeks (T-LP) and 10 healthy controls. All subjects
      were measured at three predefined sites (foot, ankle and lower leg). All groups
      except U-LP were measured by three blinded investigators. Using a handheld
      device, a 300-MHz electromagnetic wave is transmitted into the skin via a 2.5-mm
      depth probe. TDC calculated from the reflected wave is directly proportional to
      tissue water content ranging from 1 (vacuum) to 78.5 (pure water). RESULTS: Mean
      +/- SD TDC values for U-LP were 48.8 +/- 5.2. TDC values of T-LP, LipP and
      controls were 34.0 +/- 6.6, 29.5 +/- 6.2 and 32.3 +/- 5.7, respectively. U-LP had
      significantly higher TDC values in all measurement sites compared with all other
      groups (P < 0.001). A cut-off value of 40 for ankle and lower-leg measurements
      correctly differentiated all U-LP from LipP and controls. Intraclass correlation
      coefficients were 0.94 for the ankle and the lower leg and 0.63 for the foot.
      CONCLUSIONS: TDC values of U-LP were significantly higher than those of T-LP,
      LipP and controls and may aid in differentiating lymphoedema from lipoedema.
      Interobserver agreement was high in ankle and lower-leg measurements but low in
      foot measurements.

PMID- 24033280
TI  - Gemtuzumab ozogamicin for treatment of newly diagnosed acute myeloid leukaemia: a
      systematic review and meta-analysis.
AB  - Evidence regarding the efficacy of gemtuzumab ozogamicin (GO) addition to
      standard induction chemotherapy in newly diagnosed acute myeloid leukaemia (AML)
      is conflicting. This systematic review aimed to identify and summarize all
      evidence regarding the benefits and harms of adding GO to conventional
      chemotherapy for induction treatment of AML. A comprehensive literature search of
      two databases (PUBMED and Cochrane) from inception up to November 22, 2012, and 4
      years of proceedings from four major haematology/oncology conferences was
      undertaken. Endpoints included benefits (complete remission, relapse-free, event
      free, and overall survival), and harms (early mortality and incidence of hepatic
      veno-occlusive disease/sinusoidal obstructive syndrome). Seven trials (3942
      patients) met all inclusion criteria. Addition of GO showed improved relapse-free
      [Hazard Ratio (HR) = 0.84 (95% confidence interval (CI) 0.71-0.99)] and event
      free survival [HR = 0.59 (95%CI 0.48-0.74)] but not overall survival [HR = 0.95
      (95%CI 0.83-1.08)]. Addition of GO resulted in higher rate of early mortality
      [Risk Ratio = 1.60 (95%CI 1.07-2.39)]. Improved overall survival was observed in
      studies using a lower cumulative GO dose (<6 mg/m(2) ) [HR = 0.89 (95%CI 0.81
      0.99)]. Addition of GO to conventional chemotherapy as induction therapy may
      improve relapse-free and event-free survival, but does not impact overall
      survival and significantly increases early mortality in AML. 

PMID- 24033281
TI  - Evaluating pharmacokinetics and toxicity of luminescent quantum dots.
AB  - INTRODUCTION: Luminescent quantum dots (QDs) are widely utilized in the field of
      biology and medicine due to their excellent optical properties. The ultimate goal
      of QD research is the fabrication of favorable luminescent nanoprobes or
      nanocarriers. However, their toxicity and pharmacokinetics, in the human body,
      are of crucial concern and must be thoroughly investigated before QDs are used in
      clinical applications. AREAS COVERED: This review summarizes the recent
      developments of toxicity and pharmacokinetics with QDs. Furthermore, the article
      explains the pathway of QD absorption in living systems as well as the
      distribution and clearance of QDs. The authors also highlight the effects of the
      physicochemical characteristics of QDs on the toxicity and pharmacokinetics in
      animals. EXPERT OPINION: Although the toxicity and pharmacokinetics of different
      luminescent QDs have been investigated, most of these studies have focused on the
      behaviors of II B-VI A and III A-V A QDs in rodents. Investigations of the IV A
      QDs are still in an early stage. One other shortcoming in the current research is
      the lack of different animal models, especially primates, which are needed in
      addition to the current rodent models.

PMID- 24033282
TI  - The effect of gut microbiota on drug metabolism.
AB  - INTRODUCTION: Numerous drugs and toxicants must be metabolized to an active form.
      Metabolic activation by host tissues, such as the liver, has been well studied.
      However, drug and toxicant metabolism by the intestinal microbiota is an
      unexplored, but essential, field of study in pharmacology and toxicology. The
      taxonomic diversity and sheer numbers of the intestinal microbiota, and their
      capacity to metabolize xenobiotics, underscore the importance of this mode of
      metabolism. AREAS COVERED: Metabolism by the intestinal microbiota has focused on
      the natural products of glycosides hydrolyzed by intestinal microbiota enzymes,
      but not by host tissues. Metabolism of synthetic drugs by the intestinal
      microbiota has been less-intensively investigated. This review provides an
      overview of xenobiotic metabolism by the intestinal microbiota of both natural
      products and synthetic drugs. EXPERT OPINION: Metabolism by the intestinal
      microbiota might result in a different metabolite profile than that produced by
      host tissues. This could potentially result in either activation or inactivation
      of the pharmacological and/or toxicological actions of the compound in question.
      The contribution of the intestinal microbiota to drug metabolism remains
      relatively unexplored. Therefore, studies of xenobiotic metabolism by the
      intestinal microbiota need to be included in new drug development as well as
      classical studies of host tissue metabolism.

PMID- 24033284
TI  - Application of atmospheric pressure photo ionization hydrogen/deuterium exchange
      high-resolution mass spectrometry for the molecular level speciation of nitrogen
      compounds in heavy crude oils.
AB  - We report here for the first time the application of atmospheric pressure photo
      ionization hydrogen/deuterium exchange (APPI HDX) coupled to high-resolution mass
      spectrometry for molecular level speciation of nitrogen containing compounds in
      crude oils. The speciation was done based on different combinations of ions
      produced from nitrogen containing compounds with various functional groups. To
      prove the concept, 20 nitrogen containing standard compounds were analyzed. As a
      result, it was shown that the nitrogen containing compound (M) with a primary
      amine functional group mainly produced a combination of [M - 2H + 2D](*+) and ([M
      - 2H + 2D] + D)(+) ions, one with a secondary amine including alkylated or
      phenylated pyrrole a combination of [M - H + D](*+) and ([M - H + D] + D)(+), one
      with a tertiary amine including N-alkylated or phenylated pyrrole a combination
      of [M](*+) and [M + D](+), and one with a pyridine functional group mostly [M +
      D](+) ions. The concept was successfully applied to do nitrogen speciation of
      resins fractions of two oil samples. Combined with the subsequent investigation
      of double bond equivalence distribution, it was shown that resins of Qinhuangdao
      crude oil sample contained mostly alkylated pyrrole and N-alkylated pyrrole type
      compounds but resins of shale oil extract contained mostly pyridine type nitrogen
      compounds. It was also shown that the speciation of individual elemental
      composition was also possible by use of this method. Overall, this study clearly
      shows that atmospheric pressure photo ionization hydrogen/deuterium exchange
      (APPI HDX) coupled to high-resolution mass spectrometry is a powerful analytical
      method to do nitrogen speciation of crude oil compounds at the molecular level. 

PMID- 24033285
TI  - Beliefs about thought probability: evidence for persistent errors in mindreading
      and links to executive control.
AB  - Four- to 10-year-olds' and adults' (N = 263) ability to inhibit privileged
      knowledge and simulate a naive perspective were examined. Participants viewed
      pictures that were then occluded aside from a small ambiguous part. They offered
      suggestions for how a naive person might interpret the hidden pictures, as well
      as rated the probability that a naive person would think of several different
      pictures (with one picture being the actual item). Results indicated a
      significant increase between ages 4 and 7 years in attributing novel
      interpretations; however, all age groups overestimated the probability that a
      naive person could guess the actual pictures. Individual differences in working
      memory and inhibitory control predicted participants' thought suggestions as well
      as aspects of their probability judgments.

PMID- 24033286
TI  - Retrotransposon BARE displays strong tissue-specific differences in expression.
AB  - The BARE retrotransposon comprises c. 10% of the barley (Hordeum vulgare) genome.
      It is actively transcribed, translated and forms virus-like particles (VLPs). For
      retrotransposons, the inheritance of new copies depends critically on where in
      the plant replication occurs. In order to shed light on the replication strategy
      of BARE in the plant, we have used immunolocalization and in situ hybridization
      to examine expression of the BARE capsid protein, Gag, at a tissue-specific
      level. Gag is expressed in provascular tissues and highly localized in companion
      cells surrounding the phloem sieve tubes in mature vascular tissues. BARE Gag and
      RNA was not seen in the shoot apical meristem of young seedlings, but appeared,
      following transition to flowering, in the developing floral spike. Moreover, Gag
      has a highly specific localization in pre-fertilization ovaries. The strong
      presence of Gag in the floral meristems suggests that newly replicated copies
      there will be passed to the next generation. BARE expression patterns are
      consistent with transcriptional regulation by predicted response elements in the
      BARE promoter, and in the ovary with release from epigenetic transcriptional
      silencing. To our knowledge, this is the first analysis of the expression of
      native retrotransposon proteins within a plant to be reported. 

PMID- 24033287
TI  - Unbiased next generation sequencing analysis confirms the existence of autosomal
      dominant Alport syndrome in a relevant fraction of cases.
AB  - The mode of inheritance of Alport syndrome (ATS) has long been controversial. In
      1927, the disease was hypothesized as a dominant condition in which males were
      more severely affected than females. In 1990, it was considered an X-linked (XL)
      semidominant condition, due to COL4A5 mutations. Later on, a rare autosomal
      recessive (AR) form due to COL4A3/COL4A4 mutations was identified. An autosomal
      dominant (AD) form was testified more recently by the description of some large
      pedigrees but the real existence of this form is still questioned by many and its
      exact prevalence is unknown. The introduction of next generation sequencing (NGS)
      allowed us to perform an unbiased simultaneous COL4A3-COL4A4-COL4A5 analysis in
      87 Italian families (273 individuals) with clinical suspicion of ATS. In 48 of
      them (55%), a mutation in one of the three genes was identified: the inheritance
      was XL semidominant in 65%, recessive in 4% and most interestingly AD in 31% (15
      families). The AD form must therefore be seriously taken into account in all
      pedigrees with affected individuals in each generation. Furthermore, a high
      frequency of mutations (>50%) was shown in patients with only 1 or 2 clinical
      criteria, suggesting NGS as first-level analysis in cases with a clinical
      suspicion of ATS. 

PMID- 24033288
TI  - Microbial translocation and metabolic and body composition measures in treated
      and untreated HIV infection.
AB  - Circulating levels of microbial products such as lipopolysaccharide (LPS) are
      increased in HIV infection. Microbial translocation promotes obesity, insulin
      resistance, and dyslipidemia in other settings. We examined data from 178
      subjects: an Indiana University (IU) cross-sectional study [N=49 on
      antiretroviral therapy (ART), N=47 not on ART], and a 24 week prospective study
      of ART initiation ACTG 5152s (N=82). Pearson correlations were used to describe
      relationships of plasma LPS levels and soluble CD14 (sCD14), a marker of monocyte
      activation, with metabolic and body composition measures. HOMA-IR (a measure of
      insulin resistance) and LPS were correlated for the combined cohorts (r=0.19,
      p=0.02), particularly in the 5152s ART-naive cohort (r=0.41, p<0.01).
      Triglycerides were correlated with LPS in the combined cohort (r=0.32, p<0.01),
      and all subsets excluding the IU on ART subset. There were negative correlations
      between sCD14 and high-density lipoprotein (HDL) cholesterol in all subjects (r=
      0.21, p<0.01), as well as the IU subset not on ART (r=-0.32, p=0.04). Large
      particle HDL as measured by NMR spectroscopy, but not HDL cholesterol, was
      negatively correlated with LPS (r=-0.18, p=0.02), particularly among the IU
      subset receiving ART (r=-0.33, p=0.03). In the combined cohorts, sCD14 was
      negatively correlated with lean mass as well as trunk and limb fat. There is a
      relationship between microbial translocation markers and metabolic effects,
      particularly lipoproteins. During prolonged ART, microbial translocation was
      associated with an adverse effect on large HDL and thus may contribute to the
      increased cardiovascular disease risk observed during chronic treatment of HIV.

PMID- 24033290
TI  - Can you give me a hand? A comparison of hands and feet as optimal anatomical
      sites for skin conductance recording.
AB  - The fingers and feet have long been accepted as optimal anatomical recording
      sites for electrodermal activity. The available literature suggests that the feet
      are more responsive than the fingers. The present report compared skin
      conductance level (SCL) and responses (SCRs) from the left foot and the distal
      phalanges of the fingers on the nondominant hand among 19 participants. The
      principal results were (a) SCRs recorded from the fingers were significantly
      larger and more frequent with shorter latencies than SCRs from the foot, (b) SCL
      from the fingers was significantly higher than from the foot, (c) the fingers
      exhibited significantly greater discrimination conditioning than the foot, and
      (d) skin conductance measures recorded from the fingers and foot were
      significantly positively correlated. Specifically, our results demonstrate that
      the distal phalanges of the fingers are electrodermally more responsive than the
      abductor hallucis area of the foot. 

PMID- 24033289
TI  - Estrogen receptor-beta regulates human tryptophan hydroxylase-2 through an
      estrogen response element in the 5' untranslated region.
AB  - In the dorsal raphe nucleus, 17beta-estradiol (E2) increases the expression of
      the brain-specific, rate-limiting enzyme for serotonin biosynthesis, tryptophan
      hydroxylase-2 (Tph2). Although estrogen receptor beta (ERbeta) has been localized
      to Tph2 neurons, little is known about the transcriptional regulation of the Tph2
      gene by estrogen. Since the ERbeta agonist, diarylpropionitrile (DPN) also
      increases Tph2 expression, we tested the hypothesis that E2 regulates the Tph2
      promoter through direct interactions with ERbeta. A serotonergic cell line, B14,
      which endogenously expresses ERbeta was transiently transfected with a fragment
      of the human TPH2 5'-untranslated region (5'-UTR) cloned into a luciferase
      reporter vector (TPH2-luc). Treatment with E2 or DPN caused a dose-dependent
      increase of TPH2-luc activity. In contrast, E2 conjugated to bovine serum
      albumin, which is cell membrane impermeable, had no effect on TPH2-luc activity.
      An estrogen receptor (ER) antagonist blocked E2 or DPN-induced TPH2-luc activity
      suggesting a classical ER mechanism. In silico analysis revealed an estrogen
      response element (ERE) half-site located within the TPH2 5'-UTR. Deletion and
      site-directed mutation of this site abolished ligand-induced TPH2-luc activity.
      These results support the concept that there is a direct and functional
      interaction between E2:ERbeta and the ERE half-site of the TPH2 promoter to
      regulate Tph2 expression. We illustrate a direct regulation of the TPH2
      transcription by estradiol and ERbeta via a newly identified ERE half-site within
      the TPH2 promoter: (i) Estradiol- or an ERbeta agonist-induced TPH2 transcription
      was blocked by an ER antagonist, while (ii) membrane impermeable form of
      estradiol did not induce transcription. (iii) Deletion or mutation of the ERE
      half-site abolished ligand-induced TPH2 transcription. 

PMID- 24033291
TI  - Impact of polyphenols and polyphenol-rich dietary sources on gut microbiota
      composition.
AB  - Gut microbiota plays a key role in host physiology and metabolism. Indeed, the
      relevance of a well-balanced gut microbiota composition to an individual's health
      status is essential for the person's well-being. Currently, investigations are
      focused on analyzing the effects of pre- and probiotics as new therapeutic tools
      to counteract the disruption of intestinal bacterial balance occurring in several
      diseases. Polyphenols exert a wide range of beneficial health effects. However,
      although specific attention has been paid in recent years to the function of this
      "biological entity" in the metabolism of polyphenols, less is known about the
      modulatory capacity of these bioactive compounds on gut microbiota composition.
      This review provides an overview of the latest investigations carried out with
      pure polyphenols, extracts rich in polyphenols, and polyphenol-rich dietary
      sources (such as cocoa, tea, wine, soy products, and fruits) and critically
      discusses the consequences to gut microbiota composition which are produced. 

PMID- 24033292
TI  - Anti-HIV-1 integrase activity of Mimusops elengi leaf extracts.
AB  - CONTEXT: Integrase (IN) is one of the three human immunodeficiency virus type 1
      (HIV-1) enzymes that, together with a reverse transcriptase and protease, allow
      the virus to reproduce itself after infecting the host cells. Any new knowledge
      on inhibitors of this enzyme could provide essential clues for the development of
      anti-HIV drugs. OBJECTIVE: To evaluate the anti-HIV-1 IN activity of some Thai
      medicinal plant extracts, and to isolate the active compounds from the extract
      that possessed the strongest anti-HIV-1 IN activity. MATERIALS AND METHODS:
      Ethanol extracts of eight Thai medicinal plants (10-100 ug/mL) were evaluated for
      their inhibitory effect against HIV-1 IN. An extract of Mimusops elengi L.
      (Sapotaceae) leaves that possessed the strongest anti-HIV-1 IN activity was
      fractionated to isolate the active compounds by an anti-HIV-1 IN assay-guided
      isolation process. RESULTS AND DISCUSSION: The leaf extract from M. elengi had
      the strongest anti-HIV-1 IN activity with an IC50 value of 62.1 ug/mL. A bioassay
      guided isolation of the active compounds from M. elengi leaf extract resulted in
      the isolation of active compounds, identified as a mixture of gallocatechin and
      epigallocatechin. This mixture of gallocatechin and epigallocatechin showed
      satisfactory anti-HIV-1 IN activity with an IC50 value of 35.0 uM. A flavanol
      glycoside, mearnsitrin was also isolated but was inactive at a concentration of
      100 uM.

PMID- 24033293
TI  - Development and validation of an explicit aggressive beliefs and attitudes scale.
AB  - This work outlines the development and validation of a new self-report measure
      that assesses explicit aggressive beliefs and attitudes within the normal adult
      population (using 7 samples, total N = 3,533). These explicit aggressive beliefs
      and attitudes are expected to reflect aggressive biases including hostile
      attribution, potency, retribution, victimization by powerful others, derogation
      of target, and social discounting. The resulting scale is reliable with a
      hierarchical 6-factor structure, and displays convergent and discriminant
      validity. Criterion-related validity studies indicate incremental effects over
      socially desirable response bias, related implicit and explicit aggression
      measures, and is predictive of self-reported and other-reported aggression
      related behaviors. 

PMID- 24033294
TI  - A rule for designing safer nanomaterials: do not interfere with the cellular
      redox equilibrium.

PMID- 24033295
TI  - Long-term effects of post-ischaemic oestrogen on brain injury in a rat transient
      forebrain ischaemia model.
AB  - BACKGROUND: The current study was conducted to compare the effects of post
      treatment with oestrogen on histological and neurological outcomes after short (7
      day) and long (28-day) recovery periods in rats subjected to transient forebrain
      ischaemia. METHODS: Male Sprague-Dawley rats were randomly assigned to one of
      five groups: vehicle (7-day recovery period), vehicle (28-day recovery period),
      oestrogen (17beta-estradiol 200 MUg/kg, 7-day), oestrogen (17beta-estradiol 200
      MUg /kg, 28-day), or sham surgical (n = 8 in each group). After forebrain
      ischaemia was induced with bilateral carotid artery occlusion and haemorrhagic
      hypotension (mean arterial pressure = 40 mmHg) for 10 min, the brain was
      reperfused for 7 or 28 days. Either 17beta-estradiol or vehicle was injected
      intravenously during the initial 2 min of reperfusion. To evaluate histological
      damage, the number of intact neurons per 1 mm in the hippocampal CA1 subfield was
      counted at 7 or 28 days after transient forebrain ischaemia. RESULTS: At 7 days
      after ischaemia, the number of intact neurons in the hippocampal CA1 subfield was
      significantly greater in the oestrogen group [57.5 (46.5)/mm: median
      (interquartile range)] than in the vehicle group [10 (19.5) /mm; P = 0.014].
      However, there was no difference between groups at 28 days after ischaemia
      [vehicle: 11 (20)/mm vs. oestrogen: 6 (11)/mm]. The neurological deficit scores
      in the oestrogen and vehicle groups were not different from the sham group at any
      point post-ischaemia. CONCLUSION: The current study indicates that post-ischaemic
      administration of oestrogen provided short-term but not long-term neuroprotective
      effects in transient forebrain ischaemia in rats.

PMID- 24033296
TI  - Incidence of haematological malignancies by ethnic group in England, 2001-7.
AB  - The aetiology of most haematological malignancies is largely unknown. Studies of
      migrant populations can provide insights into the relative importance of genetic
      and environmental risk factors for these diseases. This study compares incidence
      rates in British Indians, Pakistanis, Bangladeshis, Black Africans, Black
      Caribbeans, Chinese and Whites in England from 2001 to 2007. We analysed 134,302
      haematological cancer registrations with ethnicity obtained by linkage to the
      Hospital Episodes Statistics database. Mid-year population estimates from 2001 to
      2007 were used. Incidence rate ratios adjusted for age, sex and income were
      calculated, comparing the six ethnic groups to Whites and to each other. Whites
      had the highest rates for most subtypes. However, Blacks experienced more than
      double the incidence of plasma cell and mature T-cell neoplasms compared to other
      ethnic groups. There were also significant differences in incidence between
      Indians, Pakistanis and Bangladeshis for Hodgkin lymphoma and mature B-cell
      neoplasms and between Black African and Black Caribbeans for mature B-cell and
      other lymphoid neoplasms (all P < 0.001). Our results show that the risk of
      haematological cancers varies greatly by ethnic group, including within those
      groups that have traditionally been grouped together (South Asians and Blacks)
      with many of these differences not explicable by known risk factors.

PMID- 24033297
TI  - Social justice and HIV vaccine research in the age of pre-exposure prophylaxis
      and treatment as prevention.
AB  - The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP)
      as means of HIV prevention raises issues of justice concerning how most fairly
      and equitably to apportion resources in support of the burgeoning variety of
      established HIV treatment and prevention measures and further HIV research,
      including HIV vaccine research. We apply contemporary approaches to social
      justice to assess the ethical justification for allocating resources in support
      of HIV vaccine research given competing priorities to support broad
      implementation of HIV treatment and prevention measures, including TasP and PrEP.
      We argue that there is prima facie reason to believe that a safe and effective
      preventive HIV vaccine would offer a distinct set of ethically significant
      benefits not provided by current HIV treatment or prevention methods. It is
      thereby possible to justify continued support for HIV vaccine research despite
      tension with priorities for treatment, prevention, and other research. We then
      consider a counter-argument to such a justification based on the uncertainty of
      successfully developing a safe and effective preventive HIV vaccine. Finally, we
      discuss how HIV vaccine research might now be ethically designed and conducted
      given the new preventive options of TasP and PrEP, focusing on the ethically
      appropriate standard of prevention for HIV vaccine trials. 

PMID- 24033300
TI  - Editorial: Recent developments in HIV vaccines.

PMID- 24033301
TI  - HIV vaccine efficacy and immune correlates of risk.
AB  - Although immune correlates of protection for HIV vaccines have remained an
      intractable question, RV144 provided the first evidence that an HIV vaccine could
      provide protective efficacy against HIV acquisition. The study of correlates of
      risk has opened large and unforeseen avenues of exploration and hope for the most
      exciting time of HIV vaccine development. Several elements in the RV144 post-hoc
      analysis and recent macaque challenge studies suggest that antibodies directed
      against the V2 loop of gp120 are functional and may have played a protective role
      against virus acquisition. Several protective mechanisms against sexual
      transmission of HIV are evoked including blocking the gp120- alpha4beta7
      interaction and ADCC although possibly mitigated by high levels of Env-specific
      IgA, both mechanisms contributing at least partially to the protective effect.
      Several questions remain unanswered that will deserve intensive assessments, in
      particular, IgG and IgA Env antibodies in mucosal secretions, Env-specific IgG
      subclasses, cross-reaction of V2 antibodies, role of T-follicular helper cells,
      and B-cell memory. Whether RV144 correlates of risk are universal and apply at
      least partially to other populations at higher risk for HIV acquisition and other
      modes of transmission (rectal, injecting drug users) is unknown and remains to be
      explored. Future efficacy trials using the same vaccine concept tested in high
      risk heterosexual populations and in men having sex with men may answer this
      question. In addition, the determination of early events in the pathogenesis
      among HIV-infected vaccine recipients based on current correlates knowledge would
      offer unprecedented information about correlates biomarkers in the peripheral
      blood and gut mucosa during early acute HIV infection. 

PMID- 24033299
TI  - Lessons learned from HIV vaccine clinical efficacy trials.
AB  - The past few years have witnessed many promising advances in HIV prevention
      strategies involving preexposure prophylaxis approaches. Some may now wonder
      whether an HIV vaccine is still needed, and whether developing one is even
      possible. The partial efficacy reported in the RV144 trial and the encouraging
      results of the accompanying immune correlates analysis suggest that an effective
      HIV vaccine is achievable. These successes have provided a large impetus and
      guidance for conducting more HIV vaccine trials. A key lesson learned from RV144
      is that assessment of HIV acquisition is now a feasible and valuable primary
      objective for HIV preventive vaccine trials. In this article we review how RV144
      and other HIV vaccine efficacy trials have instructed the field and highlight
      some of the HIV vaccine concepts in clinical development. After a long and
      significant investment, HIV vaccine clinical research is paying off in the form
      of valuable lessons that, if applied effectively, will accelerate the path toward
      a safe and effective vaccine. Together with other HIV prevention approaches,
      preventive and therapeutic HIV vaccines will be invaluable tools in bringing the
      epidemic to an end. 

PMID- 24033298
TI  - Recent advances on the use of structural biology for the design of novel envelope
      immunogens of HIV-1.
AB  - Many efforts have been made in the worldwide quest for a prophylactic HIV vaccine
      to end the AIDS pandemic, but none has yet succeeded. The lessons learned have
      repeatedly informed us that the traditional or conventional approaches directly
      using the pathogens or subunits will not be sufficient for an effective HIV/AIDS
      vaccine. Recent advances in structure-based technology have shown some promise in
      the quest for a better immunogen in HIV vaccine development. According to the
      basic binding structural relationship of an antigen and an antibody, structure
      based antigen design could bring some hope for the development of an effective
      vaccine against HIV.

PMID- 24033302
TI  - Cervical spine clearance in the traumatically injured patient: is multidetector
      CT scanning sufficient alone? Clinical article.
AB  - OBJECT: Clearance of the cervical spine in patients who have sustained trauma
      remains a contentious issue. Clinical examination alone is sufficient in
      neurologically intact patients without neck pain. Patients with neck pain or
      those with altered mental status or a depressed level of consciousness require
      further radiographic evaluation. However, no consensus exists as to the
      appropriate imaging modality. Some advocate multidetector CT (MDCT) scanning
      alone, but this has been criticized because MDCT is not sensitive in detecting
      ligamentous injuries that can often only be identified on MRI. METHODS: Patients
      were identified retrospectively from a prospectively maintained database at a
      Level I trauma center. All patients admitted between January 2004 and June 2011
      who had a cervical MDCT scan interpreted by a board-certified radiologist as
      being without evidence of acute traumatic injury and who also had a cervical MRI
      study obtained during the same hospital admission were included. Data collected
      included patient demographics, mechanism of injury, Glasgow Coma Scale score at
      the time of MRI, the indication for and findings on MRI, and the number, type,
      and indication for cervical spine procedures. RESULTS: A total of 1004 patients
      were reviewed, of whom 614 were male, with an overall mean age of 47 years. The
      indication for MRI was neck pain in 662 patients, altered mental status in 467,
      and neurological signs or symptoms in 157. The MRI studies were interpreted as
      normal in 645 patients, evidencing ligamentous injury alone in 125, and showing
      nonspecific degenerative changes in the remaining patients. Of the 125 patients
      with ligamentous injuries, 66 (52.8%) had documentation of clearance (29
      clinical, 37 with flexion-extension radiographs). Another 32 patients were
      presumed to be self-cleared, bringing the follow-up rate to 82% (98 of 119). Five
      patients died prior to clearance, and 1 patient was transferred to another
      facility prior to clearance. Based on these data, the 95% confidence interval for
      the assertion that clinically irrelevant ligamentous injury in the face of normal
      MDCT is 97%-100%. No patient with ligamentous injury on MRI was documented to
      require a surgical procedure or halo orthosis for instability. Thirty-nine
      patients ultimately underwent cervical surgical procedures (29 anterior and 10
      posterior; 5 delayed) for central cord syndrome (21), quadriparesis (9), or
      discogenic radicular pain (9). None had an unstable spine. CONCLUSIONS: In this
      study population, MRI did not add any additional information beyond MDCT in
      identifying unstable cervical spine injuries. Magnetic resonance imaging
      frequently detected ligamentous injuries, none of which were found to be unstable
      at the time of detection, during the course of admission, or on follow-up.
      Magnetic resonance imaging provided beneficial clinical information and guided
      surgical procedures in patients with neurological deficits or radicular pain. An
      MDCT study with sagittal and coronal reconstructions negative for acute injury in
      patients without an abnormal motor examination may be sufficient alone for
      clearance.

PMID- 24033303
TI  - Screw-related complications in the subaxial cervical spine with the use of
      lateral mass versus cervical pedicle screws: a systematic review.
AB  - OBJECT: Lateral mass screws (LMS) have been used extensively with a low
      complication rate in the subaxial spine. Recently, cervical pedicle screws (CPS)
      have been introduced, and are thought to provide more optimal stabilization of
      the subaxial spine in certain circumstances. However, because of the concern for
      neurovascular injury, the routine use of CPS in this location remains
      controversial. Despite this controversy, however, there are no articles directly
      comparing screw-related complications of each procedure in the subaxial cervical
      spine. The purpose of this study was to evaluate screw-related complications of
      LMS and CPS in the subaxial cervical spine. METHODS: A PubMed/MEDLINE and
      Cochrane Collaboration Library search was executed, using the key words "lateral
      mass screw" and "cervical pedicle screw." Clinical studies evaluating surgical
      procedures of the subaxial cervical spine in which either LMS or CPS were used
      and complications were reported were included. Studies in which the number of
      patients who had subaxial cervical spine surgery and the number of screws placed
      from C-3 to C-7 could not be specified were excluded. Data on screw-related
      complications of each study were recorded and compared. RESULTS: Ten studies of
      LMS and 12 studies of CPS were included in the analysis. Vertebral artery
      injuries were slightly but statistically significantly higher with the use of CPS
      relative to LMS in the subaxial cervical spine. Although the use of LMS was
      associated with a higher rate of screw loosening, screw pullout, loss of
      reduction, pseudarthrosis, and revision surgery, this finding was not
      statistically significant. CONCLUSIONS: Based on the available literature, it
      appears that perioperative neurological and late biomechanical complication
      rates, including pseudarthrosis, are similarly low for both LMS and CPS
      techniques. In contrast, vertebral artery injuries, although statistically
      significantly more common when using CPS, are extremely rare with both
      techniques, which may justify their nonroutine use in select cases. Given the
      paucity of well-designed studies available, this recommendation may be a
      reflection of deficiencies in the available studies. Surgeons using either
      technique should have intimate knowledge of cervical anatomy and an adequate
      preoperative evaluation for each patient, with the final selection based on
      individual case requirements and anatomical limitations.

PMID- 24033304
TI  - Primary surgical management by reduction and fixation of unstable hangman's
      fractures with discoligamentous instability or combined fractures: clinical
      article.
AB  - OBJECT: Several controversial issues arise in the management of unstable
      hangman's fractures. Some surgeons perform external reduction and immobilize the
      patient's neck in a halo vest, while others perform surgical reduction and
      internal fixation. The nonsurgical treatments with rigid collar or halo vest
      immobilization present problems, including nonunion, pseudarthrosis, skull
      fracture, and scalp laceration and may also fail to achieve anatomical
      realignment of the local C2-3 kyphosis. With recent advances in surgical
      technique and technology, surgical intervention is increasingly performed as the
      primary treatment in high cervical fractures. The outcomes of such surgeries are
      often superior to those of conservative treatment. The authors propose that
      surgical intervention as a primary management for hangman's fracture may avoid
      risks inherent in conservative management when severe circumferential
      discoligamentous instability is present and may reduce the risk of catastrophic
      results at the fracture site. The purposes of this study were to assess fracture
      healing following expedient reduction and surgical fixation and to propose a
      guideline for treatment of unstable hangman's fractures. METHODS: From April 2006
      to December 2011, the authors treated 105 patients with high cervical fractures.
      This study included 23 (21.9%) of these patients (15 men and 8 women; mean age
      46.4 years) with Type II, IIa, and III hangman's fractures according to the
      Levine and Edwards classification. The patient's age, sex, mechanism of injury,
      associated injuries, neurological status, and complications were ascertained. The
      authors retrospectively assessed the clinical outcome (Neck Disability Index),
      radiological findings (disc height, translation, and angulation), and bony
      healing. RESULTS: The average follow-up period was 28.9 months (range 12-63.2
      months). The overall average Neck Disability Index score at the time of this
      study was 6.6 +/- 2.3. The average duration of hospitalization was 20.3 days, and
      fusion was achieved in all cases by 14.8 +/- 1.6 weeks after surgery, as
      demonstrated on dynamic radiographs and cervical 3D CT scans. The mean
      pretreatment translation was 6.9 +/- 3.2 mm, and the mean postoperative
      translation was 1.6 +/- 1.8 mm (mean reduction 5.2 +/- 3.1 mm). The initial
      angulation was 4.7 degrees  +/- 5.3 degrees  and the postoperative angulation was
      2.5 degrees  +/- 1.8 degrees  (mean reduction 6.1 degrees  +/- 5.3 degrees ). The
      preoperative and postoperative values for translation and angulation differed
      significantly (p < 0.05). The overall C2-3 disc height was 6.7 +/- 1.2 mm
      preoperatively, whereas 3 months after surgery it was 6.4 +/- 1.1 mm. These
      values did not differ significantly (p = 0.0963). CONCLUSIONS: The authors
      observed effective reduction and bony healing in cases of unstable hangman's
      fractures after fixation, and all patients experienced favorable clinical
      outcomes with neck pain improvement. The protocols allowed for physiological
      reconstruction of the fractured deformities and avoided external fixation. The
      authors suggest that posterior reduction and screw fixation should be used as a
      primary treatment to promote stability of hangman's fracture in the presence of
      discoligamentous instability or combined fractures.

PMID- 24033305
TI  - Spinal extradural arteriovenous fistulas: clinical article.
AB  - OBJECT: Our understanding of spinal extradural arteriovenous fistulas (eAVFs) is
      relatively limited. In this study the authors aimed to provide the demographics,
      natural history, and treatment results of these rare lesions. METHODS: The
      authors performed a pooled analysis of data in the PubMed database through
      December 2012. Individualized patient data were extracted to elucidate
      demographic, clinical, and angioarchitectural features of spinal eAVFs as well as
      outcomes following different treatment strategies. RESULTS: Information on 101
      patients was extracted from 63 eligible studies. The mean patient age was 45.9
      years, and there was no significant overall sex predilection. Only 3% of the
      lesions were incidental, whereas 10% occurred in patients who had presented with
      hemorrhage. None of the 64 patients with at least 1 month of untreated follow-up
      sustained a hemorrhage over a total of 83.8 patient-years. Patients with
      lumbosacral eAVFs were significantly older (mean age 58.7 years, p < 0.0001),
      were significantly more often male (70% male, p = 0.02), had significantly worse
      presenting Aminoff-Logue motor and bladder scores (p = 0.0008 and < 0.0001,
      respectively), and had the greatest prevalence of lesions with intradural venous
      drainage (62% of cases, p < 0.0001). Neurofibromatosis Type 1 (30% of cases, p <
      0.0001) and subarachnoid hemorrhage (9% of cases, p = 0.06) were associated with
      and exclusively found in patients with cervical eAVFs. The overall complete
      obliteration rate was 91%. After a mean follow-up of 1.7 years, the clinical
      condition was improved in 89% of patients, the same in 9%, and worse in 2%.
      Obliteration rates and outcome at follow-up did not significantly differ between
      surgical and endovascular treatment modalities. CONCLUSIONS: Spinal eAVFs are
      rare lesions with a low risk of hemorrhage; they cause neurological morbidity as
      a result of mass effect and/or venous hypertension. Their treatment is associated
      with a high rate of complete obliteration and improvement in preoperative
      symptoms.

PMID- 24033307
TI  - Prediction of RNA 1H and 13C chemical shifts: a structure based approach.
AB  - The use of NMR-derived chemical shifts in protein structure determination and
      prediction has received much attention, and, as such, many methods have been
      developed to predict protein chemical shifts from three-dimensional (3D)
      coordinates. In contrast, little attention has been paid to predicting chemical
      shifts from RNA coordinates. Using the random forest machine learning approach,
      we developed RAMSEY, which is capable of predicting both (1)H and protonated
      (13)C chemical shifts from RNA coordinates. In this report, we introduce RAMSEY,
      assess its accuracy, and demonstrate the sensitivity of RAMSEY-predicted chemical
      shifts to RNA 3D structure. 

PMID- 24033306
TI  - Meditation improves self-regulation over the life span.
AB  - The use of meditation to improve emotion and attention regulation has a long
      history in Asia and there are many practitioners in Western countries. Much of
      the evidence on the effectiveness of meditation is either anecdotal or a
      comparison of long-term meditators with controls matched in age and health.
      Recently, it has been possible to establish changes in self-regulation in
      undergraduate students after only 5 days of meditation practice, allowing
      randomized trials comparing effects of meditation with other self-control methods
      such as relaxation training. Early studies took place in Chinese universities;
      however, similar effects have been obtained with U.S. undergraduates, and with
      Chinese children aged 4.5 years and older Chinese participants aged 65 years.
      Studies using neuroimaging techniques have shown that meditation improves
      activation and connectivity in brain areas related to self-regulation, and these
      findings may provide an opportunity to examine remediation of mental disorders in
      a new light. 

PMID- 24033308
TI  - Investigating groundwater flow between Edwards and Trinity aquifers in central
      Texas.
AB  - Understanding the nature of communication between aquifers can be challenging
      when using traditional physical and geochemical groundwater sampling approaches.
      This study uses two multiport wells completed within Edwards and Trinity aquifers
      in central Texas to determine the degree of groundwater inter-flow between
      adjacent aquifers. Potentiometric surfaces, hydraulic conductivities, and
      groundwater major ion concentrations and Sr isotope values were measured from
      multiple zones within three hydrostratigraphic units (Edwards and Upper and
      Middle Trinity aquifers). Physical and geochemical data from the multiport wells
      were combined with historical measurements of groundwater levels and geochemical
      compositions from the region to characterize groundwater flow and identify
      controls on the geochemical compositions of the Edwards and Trinity aquifers. Our
      results suggest that vertical groundwater flow between Edwards and Middle Trinity
      aquifers is likely limited by low permeability, evaporite-rich units within the
      Upper and Middle Trinity. Potentiometric surface levels in both aquifers vary
      with changes in wet vs. dry conditions, indicating that recharge to both aquifers
      occurs through distinct recharge areas. Geochemical compositions in the Edwards,
      Upper, and Middle Trinity aquifers are distinct and likely reflect groundwater
      interaction with different lithologies (e.g., carbonates, evaporites, and
      siliceous sediments) as opposed to mixing of groundwater between the aquifers.
      These results have implications for the management of these aquifers as they
      indicate that, under current conditions, pumping of either aquifer will likely
      not induce vertical cross-formational flow between the aquifers. Inter-flow
      between the Trinity and the Edwards aquifers, however, should be reevaluated as
      pumping patterns and hydrogeologic conditions change. 

PMID- 24033309
TI  - Ion mobility studies of carbohydrates as group I adducts: isomer specific
      collisional cross section dependence on metal ion radius.
AB  - Carbohydrates play numerous critical roles in biological systems.
      Characterization of oligosaccharide structures is essential to a complete
      understanding of their functions in biological processes; nevertheless, their
      structural determination remains challenging in part due to isomerism. Ion
      mobility spectrometry provides the means to resolve gas phase ions on the basis
      of their shape-to-charge ratios, thus providing significant potential for
      separation and differentiation of carbohydrate isomers. Here, we report on the
      determination of collisional cross sections for four groups of isomeric
      carbohydrates (including five isomeric disaccharides, four isomeric
      trisaccharides, two isomeric pentasaccharides, and two isomeric hexasaccharides)
      as their group I metal ion adducts (i.e., [M + Li](+), [M + Na](+), [M + K](+),
      [M + Rb](+), and [M + Cs](+)). In all, 65 collisional cross sections were
      measured, the great majority of which have not been previously reported. As
      anticipated, the collisional cross sections of the carbohydrate metal ion adducts
      generally increase with increasing metal ion radius; however, the collisional
      cross sections were found to scale with the group I cation size in isomer
      specific manners. Such measurements are of substantial analytical value, as they
      illustrate how the selection of charge carrier influences carbohydrate ion
      mobility determinations. For example, certain pairs of isomeric carbohydrates
      assume unique collisional cross sections upon binding one metal ion, but not
      another. On the whole, these data suggest a role for the charge carrier as a
      probe of carbohydrate structure and thus have significant implications for the
      continued development and application of ion mobility spectrometry for the
      distinction and resolution of isomeric carbohydrates. 

PMID- 24033310
TI  - Autosomal dominant PIK3R1 mutations cause SHORT syndrome.
AB  - PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy. Thauvin
      Robinet et al. (2013) The American Journal of Human Genetics 93: 141-149 SHORT
      syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase
      signalling. Chudasama et al. (2013) The American Journal of Human Genetics 93:
      150-157 Mutations in PIK3R1 cause SHORT syndrome. Dyment et al. (2013) The
      American Journal of Human Genetics 93: 158-166. 

PMID- 24033311
TI  - Zeolitic imidazolate framework-8 for fast adsorption and removal of
      benzotriazoles from aqueous solution.
AB  - 1H-benzotriazole (BTri) and 5-tolyltriazole (5-TTri) are emerging pollutants; the
      development of novel materials for their efficient adsorption and removal is thus
      of great significance in environmental sciences. Here, we report the application
      of zeolitic imidazolate framework-8 (ZIF-8) as a novel adsorbent for fast removal
      of BTri and 5-TTri in aqueous solution in view of adsorption isotherms, kinetics
      and thermodynamics, desorption, and adsorbent regeneration. The adsorption of
      BTri and 5-TTri on ZIF-8 was very fast, and most of BTri and 5-TTri were adsorbed
      in the first 2 min. The adsorption for BTri and 5-TTri follows a pseudo-second
      order kinetics and fits the Langmuir adsorption model with the adsorption
      capacity of 298.5 and 396.8 mg g(-1) for BTri and 5-TTri at 30  degrees C,
      respectively. The adsorption was a spontaneous and endothermic process controlled
      by positive entropy change. No remarkable effects of pH, ionic strength, and
      dissolved organic matter on the adsorption of BTri and 5-TTri on ZIF-8 were
      observed. The used ZIF-8 could be regenerated effectively and recycled at least
      three times without significant loss of adsorption capacity. In addition, ZIF-8
      provided much larger adsorption capacity and faster adsorption kinetics than
      activated carbon and ZIF-7. The hydrophobic and pi-pi interaction between the
      aromatic rings of the BTri and 5-TTri and the aromatic imizole rings of the ZIF
      8, and the coordination of the nitrogen atoms in BTri and 5-TTri molecules to the
      Zn(2+) ions in the ZIF-8 framework was responsible for the efficient adsorption.
      The fast adsorption kinetics, large adsorption capacity, excellent reusability as
      well as the pH, ionic strength, and dissolved organic matter insensitive
      adsorption create potential for ZIF-8 to be effective at removing benzotriazoles
      from aqueous solution. 

PMID- 24033312
TI  - Increasing concentrations of perfluoroalkyl acids in Scandinavian otters (Lutra
      lutra) between 1972 and 2011: a new threat to the otter population?
AB  - Liver samples from 140 otters (Lutra lutra) from Sweden and Norway were analyzed
      for 10 perfluoroalkyl carboxylic acids (PFCAs; C6-C15), 4 perfluoroalkane
      sulfonic acids (PFSAs; C4,C6,C8,C10) and perfluorooctane sulfonamide (FOSA).
      Perfluorooctane sulfonic acid (PFOS) was the dominant compound accounting for
      approximately 80% of the fluorinated contaminants and showing concentrations up
      to 16 MUg/g wet weight. Perfluorononanoic acid (PFNA) was the dominant PFCA (up
      to 640 ng/g wet weight) closely followed by the C10 and C11 homologues. A spatial
      comparison between otters from southwestern Norway, southern and northern Sweden
      sampled between 2005 and 2011 revealed that the samples from southern Sweden had
      generally the largest contaminant load, but two PFCAs and FOSA were higher
      concentrated in the Norwegian samples. A temporal trend study was performed on
      otters from southern Sweden collected between 1972 and 2011. Seven PFCAs (C8
      C14), PFOS and perfluorodecane sulfonic acid (PFDS) showed significantly
      increasing trends with doubling times between 5.5 and 13 years. The PFCAs also
      showed significantly increasing trends over the period 2002 to 2011. These
      findings together with the exceptionally high liver concentrations of PFOS are of
      great concern for the Scandinavian otter populations. 

PMID- 24033313
TI  - Punishment insensitivity and impaired reinforcement learning in preschoolers.
AB  - BACKGROUND: Youth and adults with psychopathic traits display disrupted
      reinforcement learning. Advances in measurement now enable examination of this
      association in preschoolers. The current study examines relations between
      reinforcement learning in preschoolers and parent ratings of reduced
      responsiveness to socialization, conceptualized as a developmental vulnerability
      to psychopathic traits. METHODS: One hundred and fifty-seven preschoolers (mean
      age 4.7 +/- 0.8 years) participated in a substudy that was embedded within a
      larger project. Children completed the 'Stars-in-Jars' task, which involved
      learning to select rewarded jars and avoid punished jars. Maternal report of
      responsiveness to socialization was assessed with the Punishment Insensitivity
      and Low Concern for Others scales of the Multidimensional Assessment of Preschool
      Disruptive Behavior (MAP-DB). RESULTS: Punishment Insensitivity, but not Low
      Concern for Others, was significantly associated with reinforcement learning in
      multivariate models that accounted for age and sex. Specifically, higher
      Punishment Insensitivity was associated with significantly lower overall
      performance and more errors on punished trials ('passive avoidance').
      CONCLUSIONS: Impairments in reinforcement learning manifest in preschoolers who
      are high in maternal ratings of Punishment Insensitivity. If replicated, these
      findings may help to pinpoint the neurodevelopmental antecedents of psychopathic
      tendencies and suggest novel intervention targets beginning in early childhood.

PMID- 24033314
TI  - Expression of a gene encoding beta-ureidopropionase is critical for pollen
      germination in tomatoes.
AB  - Global warming has seriously decreased world crop yield. High temperatures affect
      development, growth and, particularly, reproductive tissues in plants. A gene
      encoding beta-ureidopropionase (SlUPB1, EC 3.5.1.6) was isolated from the stamens
      of a heat-tolerant tomato (CL5915) using suppression subtractive hybridization.
      SlUPB1 catalyzes the production of beta-alanine, the only beta-form amino acid in
      nature. In the anthesis stage, SlUPB1 expression in CL5915 stamens, growing at
      35/30 degrees C (day/night), was 2.16 and 2.93 times greater than that in a heat
      sensitive tomato (L4783) cultivated at 30/25 degrees C or 25/20 degrees C,
      respectively. Transgenic tomatoes, upregulating SlUPB1 in L4783 and
      downregulating SlUPB1 in CL5915, were constructed, and the amount of beta-alanine
      measured by liquid chromatography-electrospray ionization-mass spectrometry in
      the transgenic overexpression of SlUPB1 was higher than that of L4783. However,
      the beta-alanine in the transgenics downregulating SlUPB1 was significantly lower
      than the beta-alanine of CL5915. Pollen germination rates of these transgenics
      were analyzed under different developmental and germinating temperatures. The
      results indicated that germination rates of transgenics overexpressing SlUPB1
      were higher than germination rates of the background tomato L4783. Germination
      rates of transgenics downregulating SlUPB1 were significantly lower than
      germination rates of background tomato CL5915, indicating the necessity of
      functional SlUPB1 for pollen germination. Pollen germinating in the buffer with
      the addition of beta-alanine further indicated that beta-alanine effectively
      enhanced pollen germination in tomatoes with low SlUPB1 expression. Together,
      these results showed that the expression of SlUPB1 is important for pollen
      germination, and beta-alanine may play a role in pollen germination under both
      optimal and high temperatures. 

PMID- 24033315
TI  - Concurrent and separate inside-out transition of platelet apoptosis and
      activation markers to the platelet surface.
AB  - The cell plasma membrane is tightly coupled with the vital processes of apoptosis
      and activation. In the current study, we investigated exposure of the apoptosis
      marker phosphatidylserine (PS) and activation marker P-selectin (CD62) on the
      plasma membrane of anucleate platelets. We found that, depending on triggering
      stimuli, the plasma membrane of human platelets may exist in four states with
      predominant exposure of (i) PS but not CD62 (75.9 +/- 2.8% of total cells), (ii)
      CD62 but not PS (86.2 +/- 1.3%), (iii) both PS and CD62 (89.6 +/- 1.0%) or (iv)
      neither PS nor CD62 (87.9-97.5%), when platelets were treated at optimal
      conditions with pro-apoptotic BH3 mimetic ABT-737, thrombin, calcium ionophore
      A23187 or control diluents, respectively. The dynamics of PS exposure induced by
      ABT-737 is a slow temperature-dependent process requiring 90 min treatment at 37
      degrees C rather than at room temperature for obtaining high levels of PS
      exposure. In contrast, thrombin-induced CD62 exposure and A23187-induced PS and
      CD62 exposure showed fast temperature-independent dynamics. This model of
      selective and concurrent stimulation of PS and/or CD62 transition to the platelet
      surface provides an experimental horizon for elucidating the roles of plasma
      membrane markers of platelet apoptosis and activation in platelet clearance. 

PMID- 24033317
TI  - Enzyme sensitive synthetic polymer micelles based on the azobenzene motif.
AB  - In this study, we investigate the potential of an artificial structural motif,
      azobenzene, in the preparation of enzyme sensitive polymeric nanostructures. For
      this purpose, an azobenzene linkage is established at the copolymer junction of
      an amphiphilic diblock copolymer. This polymer assembles into a micellar
      structure in water. Treatment with the enzyme azoreductase, in the presence of
      coenzyme NADPH, results in the cleavage of the azo-based copolymer junction and
      disruption of the micellar assembly. These results suggest that azobenezene is a
      useful non-natural structural motif for the preparation of enzyme responsive
      polymer nanoparticles. Due to the presence of azoreductase in the human
      intestine, such nanomaterials are anticipated to find applicability in the arena
      of colon-specific delivery systems. 

PMID- 24033316
TI  - The effects of performance-based rewards on neurophysiological correlates of
      stimulus, error, and feedback processing in children with ADHD.
AB  - Rewards have been shown to improve behavior and cognitive processes implicated in
      attention-deficit hyperactivity disorder (ADHD), but the information-processing
      mechanisms by which these improvements occur remain unclear. We examined the
      effect of performance-based rewards on ERPs related to processing of the primary
      task stimuli, errors, and feedback in children with ADHD and typically developing
      controls. Participants completed a flanker task containing blocks with and
      without performance-based rewards. Children with ADHD showed reduced amplitude of
      ERPs associated with processing of the flanker stimuli (P3) and errors (ERN, Pe),
      but did not differ in feedback-processing (FRN). Rewards enhanced flanker-related
      P3 amplitude similarly across groups and error-related Pe amplitude
      differentially for children with ADHD. These findings suggest that rewards may
      improve cognitive deficits in children with ADHD through enhanced processing of
      relevant stimuli and increased error evaluation. 

PMID- 24033318
TI  - Memory functioning in individuals with traumatic brain injury: an examination of
      the Wechsler Memory Scale-Fourth Edition (WMS-IV).
AB  - This study was designed to examine the construct validity of the Wechsler Memory
      Scale-Fourth Edition (WMS-IV) in individuals with traumatic brain injury (TBI).
      One hundred individuals with TBI (n = 35 complicated mild/moderate TBI; n = 65
      severe TBI) and 100 matched controls from the WMS-IV normative dataset completed
      the WMS-IV. Multivariate analyses indicated that severe TBI participants had
      poorer performance than matched controls on all index scores and subtests.
      Individuals with complicated mild/moderate TBI performed more poorly than
      controls on all index scores, as well as on tests of visual memory (Designs I and
      II; Visual Reproduction I and II) and visual working memory (Spatial Addition;
      Symbol Span), but not on auditory verbal memory tests (Logical Memory I and II;
      Verbal Paired Associates I and II). After controlling for time since injury,
      severe TBI participants had significantly lower scores than the complicated
      mild/moderate TBI on 4 of the 5 WMS-IV index scores (Auditory Memory, Visual
      Memory, Immediate Memory, Delayed Memory) and 4 of the 10 WMS-IV subtests
      (Designs I and II, Verbal Pairs II, Logical Memory II). Effect sizes for index
      and subtest scores were generally moderate for the complicated mild/moderate
      group and moderate-to-large for the severe TBI group. Findings provide support
      for the construct validity of the WMS-IV in individuals with TBI. 

PMID- 24033319
TI  - Mangiferin and its aglycone, norathyriol, improve glucose metabolism by
      activation of AMP-activated protein kinase.
AB  - CONTEXT: Mangiferin has been reported to possess antidiabetic activities.
      Norathyriol, a xanthone aglycone, has the same structure as mangiferin, except
      for a C-glucosyl bond. To our best knowledge, no study has been conducted to
      determine and compare those two compounds on glucose consumption in vitro.
      OBJECTIVE: In this study, the effects of norathyriol and mangiferin on glucose
      consumption in normal and insulin resistance (IR) L6 myotubes were evaluated.
      Simultaneously, the potential mechanism of this effect was also investigated.
      MATERIALS AND METHODS: Normal or IR L6 myotubes were incubated with norathyriol
      (2.5 ~ 10 MUM, 0.625 ~ 2.5 MUM), mangiferin (10 ~ 40 MUM, 2.5 ~ 10 MUM) or
      rosiglitazone (20 MUM) and/or 0.05 nM insulin for 24 h, respectively. The glucose
      consumption was assessed using the glucose oxidase method. Immunoblotting was
      performed to detect protein kinase B (PKB/Akt) and AMP-activated protein kinase
      (AMPK) phosphorylation in L6 myotubes cells. RESULTS: Norathyriol and mangiferin
      treatment alone increased the glucose consumption 61.9 and 56.3%, respectively,
      in L6 myotubes and made additional increasing with 0.05 nM insulin. In IR L6
      myotubes, norathyriol treatment made increasing with or without insulin,
      mangiferin treatment also made increasing but only when co-treated with insulin.
      Immunoblotting results showed that norathyriol and mangiferin produced an
      increase of 1.9 - and 1.8-fold in the phosphorylation levels of the AMPK, but not
      in Akt. DISCUSSION AND CONCLUSION: Our findings suggest that norathyriol and
      mangiferin could improve the glucose utilization and insulin sensitivity by up
      regulation of the phosphorylation of AMPK. Norathyriol may be considered as an
      active metabolite responsible for the antidiabetic activity of mangiferin.

PMID- 24033320
TI  - Occurrence, stability, and determination of formyl folates in foods.
AB  - The B-vitamin folate has specific tasks as a one-carbon (C1) group supplier in
      the building and repair of DNA and RNA as well as in the methylation of
      homocysteine to methionine. Folate occurs in all living cells as a dynamic pool
      of several interconvertible forms carrying different C1 groups. Along the food
      chain, this dynamic pool of folates constantly changes due to either enzymatic or
      chemical interconversions during food processing and storage. These
      interconversions make it difficult to determine individual folate forms in foods.
      The formyl folates, the second most predominant forms of food folates, after 5
      methyltetrahydrofolate, are particularly prone to interconvert at low pH. Today,
      this knowledge is often neglected, leading to risks for analytical
      underestimation of formyl folates. The purpose of the review is to explore the
      stability and interconversions of formyl folates in foods as well as to analyze
      the pitfalls in the determination of formyl folates. 

PMID- 24033322
TI  - My body is a cage: mechanisms and modulation of plant cell growth.
AB  - 388 I. 388 II. 389 III. 389 IV. 390 V. 391 VI. 393 VII. 394 VIII. 398 399
      References 399 SUMMARY: The wall surrounding plant cells provides protection from
      abiotic and biotic stresses, and support through the action of turgor pressure.
      However, the presence of this strong elastic wall also prevents cell movement and
      resists cell growth. This growth can be likened to extending a house from the
      inside, using extremely high pressures to push out the walls. Plants must
      increase cell volume in order to explore their environment, acquire nutrients and
      reproduce. Cell wall material must stretch and flow in a controlled manner and,
      concomitantly, new cell wall material must be deposited at the correct rate and
      site to prevent wall and cell rupture. In this review, we examine biomechanics,
      cell wall structure and growth regulatory networks to provide a 'big picture' of
      plant cell growth. 

PMID- 24033321
TI  - Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive
      pulmonary disease.
AB  - RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have
      elevated cardiovascular risk, and myocardial injury is common during severe
      exacerbations. Little is known about the prevalence, magnitude, and underlying
      mechanisms of cardiovascular risk in community-treated exacerbations. OBJECTIVES:
      To investigate how COPD exacerbations and exacerbation frequency impact
      cardiovascular risk and myocardial injury, and whether this is related to airway
      infection and inflammation. METHODS: We prospectively measured arterial stiffness
      (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with
      stable COPD. Fifty-five patients had paired stable and exacerbation assessments,
      repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was
      identified using polymerase chain reaction. MEASUREMENTS AND MAIN RESULTS: COPD
      exacerbation frequency was related to stable-state arterial stiffness (rho =
      0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent
      exacerbators (mean +/- SD aPWV, 11.4 +/- 2.1 vs. 10.3 +/- 2.0 ms(-1); P = 0.025).
      Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to
      exacerbation (n = 55) and fell slowly during recovery. In those with airway
      infection at exacerbation (n = 24) this rise was greater (1.4 +/- 1.6 vs. 0.7 +/-
      1.3 ms(-1); P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P <
      0.001). Increases in cardiac biomarkers at exacerbation were higher in those with
      ischemic heart disease (n = 12) than those without (n = 43) (mean +/- SD increase
      in troponin T, 0.011 +/- 0.009 vs. 0.003 +/- 0.006 MUg/L, P = 0.003; N-terminal
      pro-brain natriuretic peptide, 38.1 +/- 37.7 vs. 5.9 +/- 12.3 pg/ml, P < 0.001).
      CONCLUSIONS: Frequent COPD exacerbators have greater arterial stiffness than
      infrequent exacerbators. Arterial stiffness rises acutely during COPD
      exacerbations, particularly with airway infection. Increases in arterial
      stiffness are related to inflammation, and are slow to recover. Myocardial injury
      is common and clinically significant during COPD exacerbations, particularly in
      those with underlying ischemic heart disease.

PMID- 24033324
TI  - How the 2SLS/IV estimator can handle equality constraints in structural equation
      models: a system-of-equations approach.
AB  - Parameters in structural equation models are typically estimated using the
      maximum likelihood (ML) approach. Bollen (1996) proposed an alternative non
      iterative, equation-by-equation estimator that uses instrumental variables.
      Although this two-stage least squares/instrumental variables (2SLS/IV) estimator
      has good statistical properties, one problem with its application is that
      parameter equality constraints cannot be imposed. This paper presents a
      mathematical solution to this problem that is based on an extension of the
      2SLS/IV approach to a system of equations. We present an example in which our
      approach was used to examine strong longitudinal measurement invariance. We also
      investigated the new approach in a simulation study that compared it with ML in
      the examination of the equality of two latent regression coefficients and strong
      measurement invariance. Overall, the results show that the suggested approach is
      a useful extension of the original 2SLS/IV estimator and allows for the effective
      handling of equality constraints in structural equation models. 

PMID- 24033323
TI  - Adoptive gay father families: parent-child relationships and children's
      psychological adjustment.
AB  - Findings are presented on a U.K. study of 41 gay father families, 40 lesbian
      mother families, and 49 heterosexual parent families with an adopted child aged 3
      9 years. Standardized interview and observational and questionnaire measures of
      parental well-being, quality of parent-child relationships, child adjustment, and
      child sex-typed behavior were administered to parents, children, and teachers.
      The findings indicated more positive parental well-being and parenting in gay
      father families compared to heterosexual parent families. Child externalizing
      problems were greater among children in heterosexual families. Family process
      variables, particularly parenting stress, rather than family type were found to
      be predictive of child externalizing problems. The findings contribute to
      theoretical understanding of the role of parental gender and parental sexual
      orientation in child development.

PMID- 24033325
TI  - Do social relationships buffer the effects of widowhood? A prospective study of
      adaptation to the loss of a spouse.
AB  - The idea that strong social relationships can buffer the negative effects of
      stress on well-being has received much attention in existing literature. However,
      previous studies have used less than ideal research designs to test this
      hypothesis, making it difficult to draw firm conclusions regarding the buffering
      effects of social support. In this study, we examined the buffering hypothesis in
      the context of reaction and adaptation to widowhood in three large longitudinal
      datasets. We tested whether social relationships moderated reaction and
      adaptation to widowhood in samples of people who experienced loss of a spouse
      from three longitudinal datasets of nationally representative samples from
      Germany (N = 1,195), Great Britain (N = 562), and Australia (N = 298). We found
      no evidence that social relationships established before widowhood buffered
      either reaction or adaptation to the death of one's spouse. Similarly, social
      relationships that were in place during the first year of widowhood did not help
      widows and widowers recover from this difficult event. Social relationships
      acquired prior to widowhood, or those available in early stages of widowhood, do
      not appear to explain individual differences in adaptation to loss. 

PMID- 24033326
TI  - Linking ecomechanics and ecophysiology to interspecific interactions and
      community dynamics.
AB  - To predict community-level responses to climate change, we must understand how
      variation in environmental conditions drives changes in an organism's ability to
      acquire resources and translate those resources into growth, reproduction, and
      survival. This challenge can be approached mechanistically by establishing
      linkages from biophysics to community ecology. For example, body temperature can
      be predicted from environmental conditions and species-specific morphological and
      behavioral traits. Variation in body temperature within and among species
      dictates physiological performance, rates of resource acquisition, and growth.
      These ecological characteristics, along with population size, define the strength
      with which species interact. Finally, the direct (individual level) and indirect
      (community level) effects of temperature jointly determine community structure.
      This mechanistic framework can complement correlational approaches to better
      predict ecological responses to climate change and identify which characteristics
      of a species or community act as leverage points for change. Research priorities
      for further development of the mechanistic approach include documentation and
      prediction of relevant spatial and temporal variation in body temperature and the
      relationships between body temperature, individual performance, and interspecific
      interactions. 

PMID- 24033327
TI  - Alcohol modulation of cardiac matrix metalloproteinases (MMPs) and tissue
      inhibitors of MMPs favors collagen accumulation.
AB  - BACKGROUND: Chronic alcohol consumption has been shown in human and animal
      studies to result in collagen accumulation, myocardial fibrosis, and heart
      failure. Cardiac fibroblasts produce collagen and regulate extracellular matrix
      (ECM) homeostasis through the synthesis and activity of matrix metalloproteinases
      (MMPs) and tissue inhibitors of MMPs (TIMPs), with the balance of MMPs/TIMPs
      determining the rate of collagen turnover. Dynamic changes of MMP and TIMP
      expression were reported in alcohol-induced hepatic fibrosis; however, the effect
      of alcohol on MMP/TIMP balance in the heart and cardiac fibroblasts is unknown.
      We hypothesized that alcohol exposure alters cardiac fibroblast MMP and TIMP
      expression to promote collagen accumulation in the heart. METHODS: Cardiac
      fibroblasts isolated from adult rats were cultured in the presence of alcohol
      (12.5 to 200 mM) for 48 hours. MMP, TIMP, and collagen type I and III expression
      were assayed by Western blot analysis. Hydroxyproline (HPro) was used as a marker
      of collagen production. The in vivo cardiac effects of ethanol (EtOH) were
      determined using rats exposed to EtOH vapor for 2 weeks, resulting in blood
      alcohol levels of 150 to 200 mg/dl. Cardiac collagen volume fraction (CVF), as
      well as MMP, TIMP, and collagen expression, was assessed. RESULTS: EtOH-exposed
      rats exhibited up-regulation of TIMP-1, TIMP-3 and TIMP-4 in the heart, with no
      significant increases in MMPs. Cardiac fibroblasts exhibited transformation to a
      profibrotic phenotype following exposure to alcohol. These changes were reflected
      by increased alpha-smooth muscle actin and collagen I and III expression, as well
      as increased collagen secretion. In vivo EtOH exposure also produced fibrosis,
      indicated by increased CVF and expression of collagens. CONCLUSIONS: Alcohol
      exposure modulates cardiac fibroblast MMP/TIMP expression favoring a profile
      associated with collagen accumulation. Our data suggest that this disrupted
      MMP/TIMP profile may contribute to the development of myocardial fibrosis and
      cardiac dysfunction resulting from chronic alcohol abuse.

PMID- 24033329
TI  - Methylated-(3'')-epigallocatechin gallate analog suppresses tumor growth in Huh7
      hepatoma cells via inhibition of angiogenesis.
AB  - It is agreed that many of the antitumor effects of (-)-epigallocatechin gallate
      (EGCG) are mediated by various other effects. We report a new finding, namely,
      the antiproliferation potential and mechanism of methylated-(3'')
      epigallocatechin gallate analog (MethylEGCG) having a stronger anti-oxidation
      effect than EGCG. MethylEGCG inhibited activity of vascular endothelial growth
      factor (VEGF)-depended VEGF receptor 2 and p42/44 MAPK, cell proliferation, and
      tube formation in human umbilical vascular endothelial cells (HUVECs) at 1 MU M.
      Even low- dose (1.1 mg/kg i.p. 8.3 mg/kg p.o.) administration suppressed tumor
      growth in xenografted Huh7 hepatoma mice by 50%. CD31 positive cells, visualized
      in blood vessels, were reduced in tumors by 18%, suggesting high antitumor
      activity via inhibition of angiogenesis. This study indicated that the
      modification of the 3'' position methylation of EGCG (MethylEGCG) could reduce
      cell growth effects at a low concentration in vivo. 

PMID- 24033328
TI  - Molecular findings and clinical data in a cohort of 150 patients with
      anophthalmia/microphthalmia.
AB  - Anophthalmia and microphthalmia (AM) are the most severe malformations of the
      eye, corresponding respectively to reduced size or absent ocular globe. Wide
      genetic heterogeneity has been reported and different genes have been
      demonstrated to be causative of syndromic and non-syndromic forms of AM. We
      screened seven AM genes [GDF6 (growth differentiation factor 6), FOXE3 (forkhead
      box E3), OTX2 (orthodenticle protein homolog 2), PAX6 (paired box 6), RAX (retina
      and anterior neural fold homeobox), SOX2 (SRY sex determining region Y-box 2),
      and VSX2 (visual system homeobox 2 gene)] in a cohort of 150 patients with
      isolated or syndromic AM. The causative genetic defect was identified in 21% of
      the patients (32/150). Point mutations were identified by direct sequencing of
      these genes in 25 patients (13 in SOX2, 4 in RAX, 3 in OTX2, 2 in FOXE3, 1 in
      VSX2, 1 in PAX6, and 1 in GDF6). In addition eight gene deletions (five SOX2, two
      OTX2 and one RAX) were identified using a semi-quantitative multiplex polymerase
      chain reaction (PCR) [quantitative multiplex PCR amplification of short
      fluorescent fragments (QMPSF)]. The causative genetic defect was identified in
      21% of the patients. This result contributes to our knowledge of the molecular
      basis of AM, and will facilitate accurate genetic counselling. 

PMID- 24033330
TI  - Latex-less opium poppy: cause for less latex and reduced peduncle strength.
AB  - A genotype 'Sujata' developed earlier at CSIR-CIMAP from its parent 'Sampada' is
      considered to be the latex-less variety of Papaver somniferum. These two
      genotypes are contrasting in terms of latex and stem strength. Earlier we have
      carried out microarray analysis to identify differentially expressing genes from
      the capsules of the two genotypes. In this study, the peduncles of the two
      genotypes were compared for the anatomy revealing less number of laticifers in
      the cortex and vascular bundles. One of the important cell wall-related genes
      (for laccase) from the microarray analysis showing significantly higher
      expression in 'Sampada' capsule was taken up for further characterization in the
      peduncle here. It was functionally characterized through transient overexpression
      and RNAi suppression in 'Sujata' and 'Sampada'. The increase in acid insoluble
      lignin and total lignin in overexpressed tissue of 'Sujata', and comparable
      decrease in suppressed tissue of 'Sampada', along with corresponding increase and
      decrease in the transcript abundance of laccase confirm the involvement of
      laccase in lignin biosynthesis. Negligible transcript in phloem compared to the
      xylem tissue localized its expression in xylem tissue. This demonstrates the
      involvement of P. somniferum laccase in lignin biosynthesis of xylem, providing
      strength to the peduncle/stem and preventing lodging. 

PMID- 24033331
TI  - Radiofrequency catheter ablation for supraventricular tachycardia: a comparison
      study of children aged 0-4 and 5-9 years.
AB  - BACKGROUND: The safety and effectiveness of radiofrequency catheter ablation
      (RFCA) for supraventricular tachycardia (SVT) in young children was investigated.
      METHODS: Ninety-five children who underwent RFCA procedures were stratified
      according to age (group 1, 0-4 years, n = 24; group 2, 5-9 years, n = 71) and
      were evaluated retrospectively. RESULTS: Among the 95 patients, atrioventricular
      reentrant tachycardia was 78.9%, atrioventricular nodal reentrant tachycardia was
      10.5%, and ectopic atrial tachycardia was 8.4%. The acute success rate of RFCA
      was 97.9% and the recurrence rate was 11.6%. RFCA was performed for different
      main reasons in each group, including drug-resistant tachycardia (37.5% in group
      1 vs 7% in group 2; P = 0.001) and symptomatic tachycardia (4.2% in group 1 vs
      57.7% in group 2; P < 0.001). There was no significant difference in success
      rate, recurrence rate, and procedure and fluoroscopy duration between the two
      groups. The acute success rates did not differ significantly between patients
      with a single accessory pathway (AP) and those with multiple APs; however,
      failure or recurrence was more common in the patients with multiple APs (38.5% vs
      11.5%; P = 0.01). The multiple APs were found frequently on the right side (P =
      0.005). Septal dyskinesia with left ventricular dysfunction in Wolff-Parkinson
      White syndrome and tachycardia-induced cardiomyopathy improved after RFCA.
      CONCLUSIONS: RFCA was found to be effective and safe for SVT in young children.

PMID- 24033332
TI  - Electrical resistivity characterization of anisotropy in the Biscayne Aquifer.
AB  - Electrical anisotropy occurs when electric current flow varies with azimuth. In
      porous media, this may correspond to anisotropy in the hydraulic conductivity
      resulting from sedimentary fabric, fractures, or dissolution. In this study, a 28
      electrode resistivity imaging system was used to investigate electrical
      anisotropy at 13 sites in the Biscayne Aquifer of SE Florida using the rotated
      square array method. The measured coefficient of electrical anisotropy generally
      ranged from 1.01 to 1.12 with values as high as 1.36 found at one site. The
      observed electrical anisotropy was used to estimate hydraulic anisotropy (ratio
      of maximum to minimum hydraulic conductivity) which ranged from 1.18 to 2.83. The
      largest values generally were located on the Atlantic Coastal Ridge while the
      lowest values were in low elevation areas on the margin of the Everglades to the
      west. The higher values of anisotropy found on the ridge may be due to increased
      dissolution rates of the oolitic facies of the Miami formation limestone compared
      with the bryozoan facies to the west. The predominate trend of minimum
      resistivity and maximum hydraulic conductivity was E-W/SE-NW beneath the ridge
      and E-W/SW-NE farther west. The anisotropy directions are similar to the
      predevelopment groundwater flow direction as indicated in published studies. This
      suggests that the observed anisotropy is related to the paleo-groundwater flow in
      the Biscayne Aquifer. 

PMID- 24033333
TI  - The behavioral impact of baroreflex function: a review.
AB  - The baroreflex consists of a negative feedback loop adjusting heart activity to
      blood pressure fluctuations. This review is concerned with interactions between
      baroreflex function and behavior. In addition to changes in baroreflex cardiac
      control subject to behavioral manipulations, interindividual differences in
      reflex function predicted psychological and central nervous features. The
      sensitivity of the reflex was inversely related to cognitive performance, evoked
      potential amplitudes, experimental pain sensitivity, and the severity of clinical
      pain. Possible variables moderating the strength of the associations are tonic
      blood pressure, gender, and psychiatric disease. It is suggested that these
      observations reflect inhibition of higher brain function by baroreceptor
      afferents. While in many cases increased baroreflex function implies stronger
      inhibition, individual and situational factors modulate the behavioral impact of
      cardiac regulation. 

PMID- 24033334
TI  - Mechanism of formation of trans fatty acids under heating conditions in triolein.
AB  - To elucidate the relationship between heat-induced cis/trans isomerization and
      reaction temperature and energy in unsaturated lipids, we investigated the
      molecular mechanism of the heat-induced cis/trans isomerization of 18:1 isomers.
      Triolein (18:1,9c) was heated at two range temperatures (130, 160, 190, 220 
      degrees C and 135, 140, 145, 150, 155  degrees C) and analyzed by the gas
      chromatography (GC) method. When the heating temperature increased to 150 
      degrees C, the amount of trans 18:1n-9 changed from 0.0897 mg/g oil (1 h) to
      0.1700 mg/g oil (3 h). This study shows that the cis to trans isomerization may
      occur at 150  degrees C. The formation of fatty acid isomers followed a proton
      transfer route. All key geometries, transition states, intermediates, and bond
      dissociation energies (BDE) were optimized at the B3LYP/6-31G* level for the
      density functional theory (DFT). The zero-point energy corrections of the isomers
      were carried out using calculations at the B3LYP/6-311++G** level. The calculated
      energy difference between the cis and trans oleic acid was equal to 7.6 kJ/mol,
      and the energy barriers of the transition from cis 18:1n-9 to trans 18:1n-9 were
      294.5 kJ/mol. The intrinsic reaction coordinates (IRCs) were obtained to be used
      as an expression of the reaction route and to analyze the transition states and
      intermediates. The study results suggest that the heating temperature should be
      kept under 150  degrees C, to avoid the risk of trans fatty acid (TFA) intake in
      daily food. 

PMID- 24033335
TI  - The volume of nonneoplastic parenchyma in a minimally invasive partial
      nephrectomy specimen: predictive factors and impact on renal function.
AB  - PURPOSE: To identify predictors of nonneoplastic parenchymal volume excised
      during minimally invasive partial nephrectomy (PN) and determine the impact on
      postoperative renal function. PATIENTS AND METHODS: A total of 206 patients
      underwent laparoscopic or robot-assisted PN between 2003 and 2011. Parenchymal
      volume was estimated by subtraction of calculated tumor volume from total
      specimen volume. Univariate and multivariate regression analyses were used to
      examine the association of parenchymal volume with tumor and surgical factors.
      Percent and absolute changes in estimated glomerular filtration rate (eGFR) on
      the day after surgery, 1 to 12 months, and >12 months after surgery were
      correlated with parenchymal volume. RESULTS: Increased tumor size (P<0.001),
      earlier era of surgery (P=0.04), and longer ischemia time (P=0.05) were
      associated with higher parenchymal volume. Robotic surgery was not associated
      with better parenchymal preservation. Median percent change in eGFR at 1 to 12
      months (mean=6.7 months) and >12 months (mean=28.3 months) was -10.9% and -12.1%,
      respectively. No association was found between the volume of parenchyma and
      change in eGFR. Longer ischemia time was associated with decrease in eGFR only
      the first day after surgery (P=0.005). Higher body mass index BMI and Charlson
      comorbidity index and lower preoperative eGFR were associated with decrease in
      eGFR 1 to 12 months after surgery (P=0.006, 0.04, 0.001, respectively).
      CONCLUSIONS: In our cohort, larger tumors, longer ischemia time, and earlier era
      of PN were associated with increased amount of nonneoplastic parenchyma excised
      during surgery. We did not observe a relationship between absolute volume of
      parenchyma and change in renal function after surgery. Baseline renal function
      and comorbidities were the strongest determinants of long-term renal function.

PMID- 24033336
TI  - Milk flow obstruction caused by varicose vein of the teat in dairy cattle.
AB  - OBJECTIVE: To describe varicose vein as a cause of obstruction of the teat
      cistern in dairy cattle and to report therapeutic options and outcome. STUDY
      DESIGN: Retrospective case series. ANIMALS: Dairy cows (n = 22). METHODS: Medical
      records (1998-2011) of dairy cows admitted for milking difficulties caused by a
      teat varicose vein were reviewed. Three treatment approaches were used:
      sclerotherapy, ligation of the vein associated with sclerotherapy, and
      phlebectomy. Long-term outcome was obtained >= 6 months after treatment and
      defined as a milking improvement. Descriptive statistics were used to determine
      the population at risk and a chi square test was used to evaluate the
      relationship between treatments and outcomes. RESULTS: Twenty-four teats (22
      cows) had a varicose vein. Forequarters were more frequently affected than rear
      quarters (P < .01). Three sclerotherapies, 12 ligations associated with
      sclerotherapy and 6 phlebectomies were performed. Five veins were not treated.
      Overall prognosis with treatment was good (84%) at >= 6 months and was not
      significantly different between treatment types (P = .38). Recurrence of the
      obstruction by the varicose vein occurred in 3 of 19 teats. CONCLUSIONS AND
      CLINICAL RELEVANCE: Several surgical options are available for treatment of teat
      varicose veins. The overall prognosis of return to normal milking is good.

PMID- 24033338
TI  - Individual and organisational factors influencing registered nurses' attitudes
      towards patient advocacy in Swedish community health care of elders.
AB  - AIM: The aim of this study was to describe and explore individual and
      organisational factors potentially influencing registered nurses' (RNs) attitudes
      towards patient advocacy. METHODS AND SAMPLE: In a quantitative cross-sectional
      study, data were collected from 226 RNs in community health care of elders. A
      questionnaire was used to measure a number of factors including attitudes towards
      patient advocacy, nursing competence, personality traits, individual preferences
      regarding the quality of health care and working climate. A multiple regression
      analysis was performed. RESULTS: The results showed that individual factors of
      nursing competence and individual preferences of the quality of health care, as
      well as organisational factors of the working climate, explained 26.2% of the
      variance in the RNs' attitudes towards patient advocacy. CONCLUSIONS: Although
      the mentioned individual factors may be intertwined, the conclusion is that both
      individual and organisational factors influenced RNs' attitudes towards patient
      advocacy. The results do not verify that nursing experience, workplace
      experience, educational level or personality traits influence the RNs' attitudes
      towards patient advocacy. The proportion of explained variance indicates that
      additional factors also influence attitudes towards patient advocacy, and more
      research is needed to shed further light on these factors.

PMID- 24033337
TI  - Tuftsin signals through its receptor neuropilin-1 via the transforming growth
      factor beta pathway.
AB  - Tuftsin (Thr-Lys-Pro-Arg) is a natural immunomodulating peptide found to
      stimulate phagocytosis in macrophages/microglia. Tuftsin binds to the receptor
      neuropilin-1 (Nrp1) on the surface of cells. Nrp1 is a single-pass transmembrane
      protein, but its intracellular C-terminal domain is too small to signal
      independently. Instead, it associates with a variety of coreceptors. Despite its
      long history, the pathway through which tuftsin signals has not been described.
      To investigate this question, we employed various inhibitors to Nrp1's
      coreceptors to determine which route is responsible for tuftsin signaling. We use
      the inhibitor EG00229, which prevents tuftsin binding to Nrp1 on the surface of
      microglia and reverses the anti-inflammatory M2 shift induced by tuftsin.
      Furthermore, we demonstrate that blockade of transforming growth factor beta
      (TGFbeta) signaling via TbetaR1 disrupts the M2 shift similar to EG00229. We
      report that tuftsin promotes Smad3 phosphorylation and reduces Akt
      phosphorylation. Taken together, our data show that tuftsin signals through Nrp1
      and the canonical TGFbeta signaling pathway. Despite the 40-year history of the
      tetrapeptide tuftsin (TKPR), a macrophage and microglial activator, its mechanism
      of action has not been defined. Here, we report that the tuftsin-mediated anti
      inflammatory M2 shift in microglia is caused specifically by tuftsin binding to
      the receptor neuropilin-1 (Nrp1) and signaling through TGFbeta receptor-1, a
      coreceptor of Nrp1. We further show that tuftsin signals via the canonical
      TGFbeta pathway and promotes TGFbeta release from target cells. 

PMID- 24033339
TI  - Pharmacokinetic/pharmacodynamic relationship of marbofloxacin against Pasteurella
      multocida in a tissue-cage model in yellow cattle.
AB  - The fluoroquinolone antimicrobial drug marbofloxacin was administered to yellow
      cattle intravenously and intramuscularly at a dose of 2 mg/kg of body weight in a
      two-period crossover study. The pharmacokinetic properties of marbofloxacin in
      serum, inflamed tissue-cage fluid (exudate), and noninflamed tissue-cage fluid
      (transudate) were studied by using a tissue-cage model. The in vitro and ex vivo
      activities of marbofloxacin in serum, exudate, and transudate against a
      pathogenic strain of Pasteurella multocida (P. multocida) were determined.
      Integration of in vivo pharmacokinetic data with the in vitro MIC provided mean
      values for the area under the curve (AUC)/MIC for serum, exudate, and transudate
      of 155.75, 153.00, and 138.88, respectively, after intravenous dosing and 160.50,
      151.00, and 137.63, respectively, after intramuscular dosing. After intramuscular
      dosing, the maximum concentration/MIC ratios for serum, exudate, and transudate
      were 21.13, 9.13, and 8.38, respectively. The ex vivo growth inhibition data
      after intramuscular dosing were fitted to the inhibitory sigmoid Emax equation to
      provide the values of AUC/MIC required to produce bacteriostasis, bactericidal
      activity, and elimination of bacteria. The respective values for serum were
      17.25, 31.29, and 109.62, and slightly lower values were obtained for transudate
      and exudate. It is proposed that these findings might be used with MIC50 or MIC90
      data to provide a rational approach to the design of dosage schedules which
      optimize efficacy in respect of bacteriological as well as clinical cures. 

PMID- 24033340
TI  - Reliability of quantification measures of actinic keratosis.
AB  - BACKGROUND: Enumerating actinic keratoses (AKs) is highly variable but important
      to standardize as new therapies are emerging. OBJECTIVES: To assess the
      reliability of four different methods used to quantify AKs and to investigate
      whether a consensus meeting affects the reliability. METHODS: This was a single
      blinded study of 12 experienced dermatologist raters counting AKs on the face and
      ears of nine subjects before and after a consensus meeting. Raters were recruited
      from investigators of a multicentre Veterans Affairs cooperative study. The
      intraclass correlation coefficient (ICC) among raters for pre- and post-consensus
      evaluations was the primary outcome measure. RESULTS: Of the four assessment
      methods, the 'total count' method had the greatest ICC for both pre- (0.18, P =
      0.04) and post-consensus (0.66, P = < 0.0001) assessments. Total count was also
      the only pre-consensus ICC for which the null hypothesis of no association among
      assessments was rejected. CONCLUSIONS: Total AK count appears to be the most
      reliable measure of quantifying AKs on the face and ears. Educational consensus
      discussion prior to assessment improves reliability of this measure.

PMID- 24033341
TI  - Cooking methods and esophageal squamous cell carcinoma in high-risk areas of
      Iran.
AB  - Cooking methods have been implicated in the etiology of gastrointestinal cancers,
      reflecting exposure to potential carcinogens as results of cooking. We used a
      validated food frequency questionnaire and a pretested cooking method
      questionnaire in 3 groups: 40 esophageal squamous cell carcinoma (ESCC) cases
      from a high-risk area in northeast of Iran, 40 healthy subjects from the same
      high-risk area, and 40 healthy subjects from a low-risk area in Southern Iran. We
      compared the frequency of boiling, grilling, and frying, and the frying score
      among these 3 groups. We also calculated "frying index" by multiplying the
      frequency of each fried food item by its frying score. Mean frying to boiling
      ratios were 18.2:1, 12.8:1, and 2.6:1 for cases, high-risk controls, and low-risk
      controls, respectively (P < 0.01). Reuse of cooking oil for frying was reported
      in 37.5% of the ESCC cases, 25% of high-risk controls, and 7.5% of low-risk
      controls (P < 0.001). Frying index was higher in the high-risk than in the low
      risk controls (P < 0.001) and in cases than in the high-risk controls (P < 0.05)
      after adjusting for smoking, opium use, rural residence, education, and
      ethnicity. High-temperature cooking and frying may be associated with increased
      risk of ESCC in high-risk areas. 

PMID- 24033342
TI  - More cells, bigger cells or simply reorganization? Alternative mechanisms leading
      to changed internode architecture under contrasting stress regimes.
AB  - Shading and mechanical stress (MS) modulate plant architecture by inducing
      different developmental pathways. Shading results in increased stem elongation,
      often reducing whole-plant mechanical stability, while MS inhibits elongation,
      with a concomitant increase in stability. Here, we examined how these organ-level
      responses are related to patterns and processes at the cellular level by exposing
      Impatiens capensis to shading and MS. Shading led to the production of narrower
      cells along the vertical axis. By contrast, MS led to the production of fewer,
      smaller and broader cells. These responses to treatments were largely in line
      with genetic differences found among plants from open and closed canopy sites.
      Shading- and MS-induced plastic responses in cellular characteristics were
      negatively correlated: genotypes that were more responsive to shading were less
      responsive to MS and vice versa. This negative correlation, however, did not
      scale to mechanical and architectural traits. Our data show how environmental
      conditions elicit distinctly different associations between characteristics at
      the cellular level, plant morphology and biomechanics. The evolution of optimal
      response to different environmental cues may be limited by negative correlations
      of stress-induced responses at the cellular level. 

PMID- 24033343
TI  - Chromium stress response effect on signal transduction and expression of
      signaling genes in rice.
AB  - Hexavalent chromium [Cr(VI)] is a non-essential metal for normal plants and is
      toxic to plants at high concentrations. However, signaling pathways and molecular
      mechanisms of its action on cell function and gene expression remain elusive. In
      this study, we found that Cr(VI) induced endogenous reactive oxygen species (ROS)
      generation and Ca(2+) accumulation and activated NADPH oxidase and calcium
      dependent protein kinase. We investigated global transcriptional changes in rice
      roots by microarray analysis. Gene expression profiling indicated activation of
      abscisic acid-, ethylene- and jasmonic acid-mediated signaling and inactivation
      of gibberellic acid-related pathways in Cr(VI) stress-treated rice roots. Genes
      encoding signaling components such as the protein kinases domain of unknown
      function 26, receptor-like cytoplasmic kinase, LRK10-like kinase type 2 and
      protein phosphatase 2C, as well as transcription factors WRKY and
      apetala2/ethylene response factor were predominant during Cr(VI) stress. Genes
      involved in vesicle trafficking were subjected to functional characterization.
      Pretreating rice roots with a vesicle trafficking inhibitor, brefeldin A,
      effectively reduced Cr(VI)-induced ROS production. Suppression of the vesicle
      trafficking gene, Exo70, by virus-induced gene silencing strategies revealed that
      vesicle trafficking is required for mediation of Cr(VI)-induced ROS production.
      Taken together, these findings shed light on the molecular mechanisms in
      signaling pathways and transcriptional regulation in response to Cr stress in
      plants.

PMID- 24033344
TI  - Malfolded protein structure and proteostasis in lung diseases.
AB  - Recent discoveries indicate that disorders of protein folding and degradation
      play a particularly important role in the development of lung diseases and their
      associated complications. The overarching purpose of the National Heart, Lung,
      and Blood Institute workshop on "Malformed Protein Structure and Proteostasis in
      Lung Diseases" was to identify mechanistic and clinical research opportunities
      indicated by these recent discoveries in proteostasis science that will advance
      our molecular understanding of lung pathobiology and facilitate the development
      of new diagnostic and therapeutic strategies for the prevention and treatment of
      lung disease. The workshop's discussion focused on identifying gaps in scientific
      knowledge with respect to proteostasis and lung disease, discussing new research
      advances and opportunities in protein folding science, and highlighting novel
      technologies with potential therapeutic applications for diagnosis and treatment.

PMID- 24033345
TI  - Optimization of extracellular truncated staphylococcal protein A expression in
      Escherichia coli BL21 (DE3).
AB  - Staphylococcal protein A (SpA) plays an important role in Staphylococcus aureus
      pathogenesis. The recombinant SpA is also widely used in biotechnology to purify
      polyclonal and monoclonal immunoglobulin G antibodies. In this study, expression
      and secretion of a truncated form of SpA containing five immunoglobulin-binding
      domains using its own native signal sequence were optimized in Escherichia coli.
      Optimization was carried out using response surface method (RSM), making use of
      the interaction between five variables. The initial results revealed that the
      signal peptide from S. aureus was recognized in E. coli and the resulting SpA was
      expressed and secreted into the medium. Compounds, such as glycine, affected the
      secretion of SpA into the culture medium. The central composite design experiment
      showed that the optimum conditions for the maximum expression of recombinant
      truncated SpA in E. coli included 10% (w/v) lactose, 1.77% (w/v) glycine,
      induction time of 11 H, an optical density (600) of 1.1, and a temperature of 33 
      degrees C. Optimization using RSM resulted in a fivefold increase in the
      secretion of SpA. To date, this is the first study of its kind regarding the
      definite influence of glycine concentration and duration of the cultivation
      period on the secretion of SpA.

PMID- 24033346
TI  - Down-regulation of EMP1 is associated with epithelial hyperplasia and metaplasia
      in nasal polyps.
AB  - AIMS: The aim of this study was to assess protein and mRNA expression of
      epithelial membrane protein 1 (EMP1) in the nasal mucosa of patients with nasal
      polyps (NP), and to determine what changes occur in response to
      glucocorticosteroid (GC) treatment. METHODS AND RESULTS: NP tissue was obtained
      from 55 patients, 18 of whom were treated with nasal GCs (i.e. these 18 patients
      had NP biopsies taken before and after treatment). Biopsies of inferior turbinate
      mucosa from 30 healthy subjects were used as controls. Quantitative PCR and
      immunohistochemistry were performed to determine the expression levels of EMP1.
      EMP1 mRNA expression was significantly lower (2.77-fold) in tissues from NP
      patients before GC treatment when compared to controls, but was increased in
      these patients after GC treatment. EMP1 staining in nasal epithelium co-localized
      with both basal (p63(+)) and differentiated (CK18(+)) epithelial cells. Their
      immunoreactivity was significantly greater in controls than NP patients. EMP1
      mRNA levels were lower in the epithelium with severe hyperplasia (1.79-fold) or
      with metaplasia (1.85-fold) as compared to those with mild to moderate
      hyperplasia or non-metaplastic epithelium, respectively. Positive correlations
      between EMP1 and other epithelial cell-related gene (e.g. JUN, PTGS2, AREG etc.)
      mRNAs were observed. CONCLUSIONS: EMP1 could be a biomarker for aberrant
      epithelial remodelling and metaplasia in chronic inflammatory upper airway mucosa
      (e.g. NP).

PMID- 24033347
TI  - Increased phosphatidylcholine concentration in saliva reduces surface tension and
      improves airway patency in obstructive sleep apnoea.
AB  - Surface tension may have important role for maintaining upper airway patency in
      patients with obstructive sleep apnoea. It has been demonstrated that elevated
      surface tension increases the pharyngeal pressures required to reopen the upper
      airway following collapse. The aim of the study was to evaluate the associations
      between the concentrations of endogenous surfactants in saliva with indices of
      upper airway patency in obstructive sleep apnoea. We studied 20 male patients
      with obstructive sleep apnoea (age: 60.3 +/- 10.3 years; BMI: 25.9 +/- 4.6 kg m(
      2); AHI: 41.5 +/- 18.6 events h(-1)). We obtained 100-MUL samples of saliva prior
      to overnight polysomnographic sleep study. The surface tension was determined
      using the pull-off force technique. The concentration of phosphatidylcholine (PC)
      was evaluated by liquid chromatography-mass spectrometry (LC-MS/MS). Regression
      analysis between apnoea, hypopnoea and apnoea/hypopnoea indices and the ratio of
      hypopnoea time/total disordered breathing time (HT/DBT) with surface tension and
      PC were performed. P < 0.05 was considered significant. The mean saliva surface
      tension was 48.8 +/- 8.0 mN m(-1) and PC concentration was 15.7 +/- 11.1 nM. The
      surface tension was negatively correlated with the PC concentration (r = -0.48, P
      = 0.03). There was a significant positive correlation between surface tension
      with hypopnoea index (r = 0.50, P = 0.03) and HT/DBT (r = 0.6, P = 0.006), but
      not apnoea or apnoea/hypopnoea index (P > 0.11). Similarly, PC concentration
      negatively correlated with hypopnoea index (r = -0.45, P = 0.04) and HT/DBT (r = 
      0.6, P = 0.004), but not with apnoea index or AHI (P > 0.08). An increase in
      salivary PC concentration may increase upper airway patency in obstructive sleep
      apnoea through a reduction in surface tension.

PMID- 24033348
TI  - Congenital ectopic toenail.

PMID- 24033349
TI  - Transfusion reaction due to Klebsiella pneumoniae-contaminated red blood cells: a
      case report.

PMID- 24033351
TI  - Confocal laser endomicroscopy in gastrointestinal and pancreatobiliary diseases.
AB  - Confocal laser endomicroscopy (CLE) is an emerging diagnostic procedure that
      enables in vivo pathological evaluation during ongoing endoscopy. There are two
      types of CLE: endoscope-based CLE (eCLE), which is integrated in the tip of the
      endoscope, and probe-based CLE (pCLE), which goes through the accessory channel
      of the endoscope. Clinical data of CLE have been reported mainly in
      gastrointestinal (GI) diseases including Barrett's esophagus, gastric neoplasms,
      and colon polyps, but, recently, a smaller pCLE, which goes through a catheter or
      a fine-needle aspiration needle, was developed and clinical data in the diagnosis
      of biliary stricture or pancreatic cysts have been increasingly reported. The
      future application of this novel technique expands beyond the pathological
      diagnosis to functional or molecular imaging. Despite these promising data, the
      generalizability of the procedure should be confirmed especially in Japan and
      other Asian countries, where the current diagnostic yield for GI luminal diseases
      is high. Given the high cost of CLE devices, cost-benefit analysis should also be
      considered.

PMID- 24033350
TI  - Infant emotional withdrawal: a precursor of affective and cognitive disturbance
      in fetal alcohol spectrum disorders.
AB  - BACKGROUND: Our aim was to test the hypothesis that emotional withdrawal is an
      early indicator of affective disorder in infants heavily exposed prenatally to
      alcohol, which is independent of alcohol-related effects on mother-infant
      interaction and temperament and discriminated between children later diagnosed
      with fetal alcohol syndrome (FAS) and partial FAS (PFAS) and predicted cognitive
      and affective outcomes at 5 and 9 years. METHODS: The sample consisted of Cape
      Coloured (mixed ancestry) infants, whose mothers were interviewed during
      pregnancy regarding their alcohol consumption using a timeline follow-back
      approach. Infant emotional withdrawal (n = 85) was assessed on the Alarm Distress
      Baby Scale at 6.5 months. Mother-infant interaction was evaluated from video
      recordings during free play and infant feeding at 6.5 months (n = 127). Infant
      temperament was assessed by maternal report on the EAS Temperament Survey at 13
      months (n = 119). Sociodemographic and psychological correlates of maternal
      alcohol use and infant iron deficiency were examined as potential confounders.
      The children were diagnosed for FAS/PFAS by expert dysmorphologists at 5 years,
      cognitive and affective function at 5 and 9 years. RESULTS: Prenatal alcohol
      exposure was associated with increased infant emotional withdrawal and decreased
      activity, but unrelated to mother-infant interaction or any other temperament
      measures. Children later diagnosed with FAS and PFAS at 5 years exhibited more
      emotional withdrawal and less responsivity and activity as infants. Infant
      withdrawal, responsivity, quality of interaction, and maternal sensitivity also
      predicted poorer IQ and affective response at 5 and 9 years. When all 4 infant
      affective measures were examined simultaneously in a regression analysis, only
      infant emotional withdrawal persisted as a significant predictor of 9-year IQ.
      CONCLUSIONS: This study is the first to document a direct effect of fetal alcohol
      exposure on emotional withdrawal in infancy. These data link prenatal alcohol to
      a specific aspect of infant affective function not attributable to mother-infant
      interaction, infant temperament, or other socioemotional aspects of the infant's
      environment and identify infant emotional withdrawal as an early indicator of
      affective disturbance, particularly in children later diagnosed with FAS and
      PFAS.

PMID- 24033352
TI  - Melatonin-enhanced autophagy protects against neural apoptosis via a
      mitochondrial pathway in early brain injury following a subarachnoid hemorrhage.
AB  - Melatonin is a strong antioxidant that has beneficial effects against early brain
      injury (EBI) following a subarachnoid hemorrhage (SAH) in rats; protection
      includes reduced mortality and brain water content. The molecular mechanisms
      underlying these clinical effects in the SAH model, however, have not been
      clearly identified. This study was undertaken to determine the influence of
      melatonin on neural apoptosis and the potential mechanism of these effects in EBI
      following SAH using the filament perforation model of SAH in male Sprague Dawley
      rats. Melatonin (150 mg/kg) or vehicle was given via an intraperitoneal injection
      2 hr after SAH induction. Brain samples were extracted 24 hr after SAH. The
      results show that melatonin treatment markedly reduced caspase-3 activity and the
      number of TUNEL-positive cells, while the treatment increased the LC3-II/LC3-I,
      an autophagy marker, which indicated that melatonin-enhanced autophagy
      ameliorated apoptotic cell death in rats subjected to SAH. To further identify
      the mechanism of autophagy protection, we demonstrated that melatonin
      administration reduced Bax translocation to the mitochondria and the release of
      cytochrome c into the cytosol. Taken together, this report demonstrates that
      melatonin improved the neurological outcome in rats by protecting against neural
      apoptosis after the induction of filament perforation SAH; moreover, the
      mechanism of these antiapoptosis effects was related to the enhancement of
      autophagy, which ameliorated cell apoptosis via a mitochondrial pathway.

PMID- 24033353
TI  - Grappling with interdisciplinary research: response to Pooley.

PMID- 24033354
TI  - Ex vivo biomechanical comparison of a 3.5 mm locking compression plate applied
      cranially and a 2.7 mm locking compression plate applied medially in a gap model
      of the distal aspect of the canine radius.
AB  - OBJECTIVE: To compare a medially applied 2.7 mm locking compression plate (LCP)
      to a cranially applied 3.5 mm LCP in a cadaveric distal radial fracture gap
      model. STUDY DESIGN: In vitro mechanical testing of paired cadaveric limbs SAMPLE
      POPULATION: Paired radii (n = 8) stabilized with either a 2.7 mm LCP medially or
      a 3.5 mm LCP cranially. METHODS: Simulated distal radial comminuted fractures
      were created and stabilized with an LCP plate on the cranial surface in 1 limb,
      and on the medial surface in the contralateral limb. Gap stiffness, gap strain,
      and failure properties were compared between cranial and medial plate positions.
      Limb constructs were axially loaded, cyclically through 4 conditions that allowed
      mediolateral or craniocaudal bending at walk and trot loads, before monotonic
      failure loading. The effects of plate position on mechanical variables were
      assessed using paired t-tests. RESULTS: Gap stiffness was greater for cranial
      plate constructs than medial plate constructs for axial loading with mediolateral
      bending, but lower with craniocaudal bending. However, in loading that
      facilitated craniocaudal bending the medial plate construct also had bending
      apparent in the mediolateral direction. Gap strains for the different conditions
      followed similar trends as stiffness. Cranial plate constructs had significantly
      higher monotonic stiffness, yield, and failure loads. CONCLUSION: The larger,
      cranially applied LCP was biomechanically superior to the smaller, medially
      applied LCP in our distal radial fracture gap model, however the medial plate was
      superior to the cranial plate in cyclic loading allowing craniocaudal bending.

PMID- 24033355
TI  - Efficacy and safety of cryoablation of parahissian accessory pathways in
      children: a single institution study.
AB  - BACKGROUND: Catheter cryoablation of supraventricular tachycardias involving the
      perinodal regions is considered to be a safer alternative compared to
      radiofrequency ablation. Limited information is available for efficacy, midterm
      outcomes, and complications regarding the ablation of parahissian accessory
      pathways (APs) in pediatric patients. METHODS: A retrospective review of all
      pediatric patients who underwent cryoablation for treatment of a parahissian AP
      was performed. RESULTS: Twenty-five patients (median age 13 years and weight 45.6
      kg) underwent cryoablation of a parahissian AP. Median number of cryolesions
      applied was four (range: 3-6). Initial procedural success was achieved in 23
      patients (23/25, 92%). Transient third-degree atrioventricular (AV) block was
      noted in two patients. There was no permanent AV block. Transient right bundle
      branch block (RBBB) was observed in one patient and permanent RBBB occurred in
      two patients. Of the patients successfully ablated with cryo, there was only one
      recurrence (1/23, 4.3%) over a follow-up of 17.5 months (range 6-34 months).
      CONCLUSION: Cryoablation of parahissian APs is both safe and effective with a low
      risk of recurrence in pediatric patients.

PMID- 24033356
TI  - Effects of fasudil on the portal and systemic hemodynamics of patients with
      cirrhosis.
AB  - BACKGROUND AND AIM: Fasudil, a Rho-kinase inhibitor, has been shown to reduce
      portal venous pressure in cirrhotic rats. However, its effects on portal and
      systemic hemodynamics have not been investigated in cirrhotic patients with
      portal hypertension. The aim of this study was to assess the effects of fasudil
      on the portal and systemic hemodynamics of cirrhotic patients with portal
      hypertension. METHODS: Twenty-three patients with cirrhosis and portal
      hypertension were studied. Systemic and portal hemodynamics were measured prior
      to and 50 min after the initiation of intravenous administration of 30 mg fasudil
      (n = 15) or placebo (n = 8). RESULTS: After fasudil, there were significant
      decreases in both mean arterial pressure (P < 0.05) and systemic vascular
      resistance (P < 0.05), whereas the heart rate increased significantly (P < 0.05).
      There was a significant decrease in the hepatic venous pressure gradient (P <
      0.05). Portal vascular resistance also decreased significantly (P < 0.01).
      Placebo caused no significant effects. There were no symptomatic reactions caused
      by changes in the mean arterial pressure or heart rate after fasudil.
      CONCLUSIONS: In cirrhotic patients with portal hypertension, fasudil lowers
      portal vascular resistance, resulting in decreased portal venous pressure with
      reducing arterial pressure.

PMID- 24033357
TI  - Patients' motives for consenting or refusing to participate in a clinical trial
      in organ transplantation.
AB  - BACKGROUND: The goal of this health-psychology study was to investigate the range
      of motives that make someone consent or refuse participation in a clinical
      transplant trial. METHODS: The study involved (i) preparatory interviews with
      five transplant patients who took part in clinical trials and five persons from
      the general public; (ii) we created a questionnaire with scaled responses; (iii)
      we selected 468 patients, divided into two groups: patients waiting for a
      transplant and patients who already had a transplant; (iv) we obtained patient
      consents, sent out the questionnaire, and recorded responses; (v) data were
      analysed using descriptive statistics, exploratory factorial analyses,
      correlations and regressions. RESULTS: Two hundred and ten patients answered the
      questionnaire. Motives were classified into the following: (i) Motives to consent
      participating in a clinical trial (pride in participating, hope for better
      quality of life, sufficient and clear information, discussion with others
      participating in a trial, altruism); or (ii) Motives to refuse participating (no
      information on medical teams, lack of explanation, fear of additional expenses,
      being considered a "guinea pig"). CONCLUSIONS: This study contributes to our
      understanding of the motivations of patients who accepted or refused
      participation in a clinical transplantation trial.

PMID- 24033358
TI  - Effects of adalimumab therapy in adult subjects with moderate-to-severe psoriasis
      on Th17 pathway.
AB  - BACKGROUND: Until relatively recently, psoriasis has been considered to be a
      mainly T helper (Th)1-driven inflammatory disease; however, several findings have
      now assessed a major role for Th17 cells in its pathogenesis. Adalimumab is a
      biological agent that inhibits TNF-alpha, a pro-inflammatory cytokine with a
      pivotal role in the mechanisms of the disease. OBJECTIVE: To elucidate the in
      vivo effects of adalimumab therapy on Th17 pathway. METHODS: Quantitative real
      time reverse transcriptase polymerase chain reaction was used to analyse levels
      of expression of Th17 polarizing cytokines (IL-23A, TGF-beta, IL-1beta, IL-6),
      Th17 cytokines (IL-17, IL-22) as well as TNF-alpha, Th1 polarizing cytokine (IFN
      alpha) and Th17 downstream effector mediators, such as chemokines (IL-8, CCL-20)
      in skin and peripheral blood mononuclear cells before and after 16 weeks of
      adalimumab therapy. Similarly, gene expression of Th17 induced mediators by
      keratinocytes (antimicrobial peptides: HBD-2, S100A7) was investigated at skin
      level. In addition, cutaneous and plasma IL-17 was examined by
      immunohistochemistry and enzyme-linked immunosorbent assay respectively. Efficacy
      of the treatment was assessed by several clinical index scores as well as
      epidermal thickness reduction. RESULTS: Adalimumab therapy led to improvement in
      skin disease scores in all patients. Moreover, adalimumab treatment down
      modulated Th17 pathway at skin level. Plasma IL-17 levels and IL-17-positive
      cells in psoriatic lesional skin were decreased by adalimumab treatment.
      CONCLUSIONS: Our data highlight that the immunomodulatory activity of adalimumab
      is associated with considerable clinical improvements as well as a potent shut
      down of Th17 response in patients with moderate-to-severe psoriasis.

PMID- 24033359
TI  - Applications and functions of food-grade phosphates.
AB  - Food-grade phosphates are used in the production of foods to function as buffers,
      sequestrants, acidulants, bases, flavors, cryoprotectants, gel accelerants,
      dispersants, nutrients, precipitants, and as free-flow (anticaking) or ion
      exchange agents. The actions of phosphates affect the chemical leavening of
      cakes, cookies, pancakes, muffins, and doughnuts; the even melt of processed
      cheese; the structure of a frankfurter; the bind and hydration of delicatessen
      meats; the fluidity of evaporated milk; the distinctive flavor of cola beverages;
      the free flow of spice blends; the mineral content of isotonic beverages; and the
      light color of par-fried potato strips. In the United States, food-grade
      phosphates are generally recognized as safe, but use levels have been defined for
      some foods by the Code of Federal Regulations, specifically Titles 9 and 21 for
      foods regulated by the U.S. Department of Agriculture (USDA) and the U.S. Food
      and Drug Administration (FDA), respectively. Standards for food purity are
      defined nationally and internationally in sources such as the Food Chemicals
      Codex and the Joint Food and Agriculture Organization and World Health
      Organization (FAO/WHO) Expert Committee on Food Additives. 

PMID- 24033361
TI  - Content validity of the Chinese version of Resilience Scale for older people.

PMID- 24033360
TI  - Metabolic products of [2-(13) C]ethanol in the rat brain after chronic ethanol
      exposure.
AB  - Most ingested ethanol is metabolized in the liver to acetaldehyde and then to
      acetate, which can be oxidized by the brain. This project assessed whether
      chronic exposure to alcohol can increase cerebral oxidation of acetate. Through
      metabolism, acetate may contribute to long-term adaptation to drinking. Two
      groups of adult male Sprague-Dawley rats were studied, one treated with ethanol
      vapor and the other given room air. After 3 weeks the rats received an
      intravenous infusion of [2-(13) C]ethanol via a lateral tail vein for 2 h. As the
      liver converts ethanol to [2-(13) C]acetate, some of the acetate enters the
      brain. Through oxidation the (13) C is incorporated into the metabolic
      intermediate alpha-ketoglutarate, which is converted to glutamate (Glu),
      glutamine (Gln), and GABA. These were observed by magnetic resonance spectroscopy
      and found to be (13) C-labeled primarily through the consumption of ethanol
      derived acetate. Brain Gln, Glu, and, GABA (13) C enrichments, normalized to (13)
      C-acetate enrichments in the plasma, were higher in the chronically treated rats
      than in the ethanol-naive rats, suggesting increased cerebral uptake and
      oxidation of circulating acetate. Chronic ethanol exposure increased
      incorporation of systemically derived acetate into brain Gln, Glu, and GABA, key
      neurochemicals linked to brain energy metabolism and neurotransmission. The liver
      converts ethanol to acetate, which may contribute to long-term adaptation to
      drinking. Astroglia oxidize acetate and generate neurochemicals, while neurons
      and glia may also oxidize ethanol. When (13) C-ethanol is administered
      intravenously, (13) C-glutamine, glutamate, and GABA, normalized to (13) C
      acetate, were higher in chronic ethanol-exposed rats than in control rats,
      suggesting that ethanol exposure increases cerebral oxidation of circulating
      acetate. 

PMID- 24033362
TI  - Dental sealants and composite restorations and longitudinal changes in immune
      function markers in children.
AB  - OBJECTIVE: Resins used in dental composites, derived from bisphenol-A (BPA), have
      been shown to alter immune cells. The objective of this study was to explore
      children's immune function changes in relation to resin composite treatment.
      DESIGN: We conducted secondary data analysis of the New England Children's
      Amalgam Trial immune function substudy (N = 59). Immune function was measured pre
      treatment and up to five times post-treatment through 5-year follow-up.
      Multivariable generalized linear regression models were used to estimate the
      association between three classes of resin composites (bisphenol-A-diglycidyl
      dimethacrylate [BisGMA]-based flowables used for preventive sealants; urethane
      dimethacrylate [UDMA]-based compomer restorations; bisGMA-based restorations) and
      changes in immune function markers measured annually. RESULTS: Total white blood
      cell counts and responsiveness of T cells or neutrophils were not appreciably
      altered by composite treatment levels. Changes in B cell responsiveness were
      greater throughout follow-up among children with more bisGMA-based composite
      restorations, which opposed findings for amalgam treatment levels. Monocyte
      responsiveness changes were decreased at 6 months with greater treatment, but not
      over longer follow-up. CONCLUSIONS: Results of this analysis showed no overt
      immune function alterations associated with resin composites. Additional research
      regarding lymphocyte activation may be warranted given the consistency of results
      within these analyses and with a prior study showing increased B cell activation.

PMID- 24033363
TI  - Comparison of the germination rates of Metarhizium spp. conidia from Japan at
      high and low temperatures.
AB  - The knowledge of the growth characteristics of entomopathogenic fungi at
      different temperatures is very important for understanding their ecology and
      field efficacy as biological control agents. However, the relationships between
      their DNA-based phylogenetic tree classifications and growth characteristics at
      different temperatures have not been adequately investigated. In this study, we
      compared the phylogenetic relationships between Metarhizium anisopliae sensu lato
      and M. flavoviride isolates obtained from soils in various environments in Japan
      and the germination rates of their conidia on agar medium in hot and cold
      conditions. The results showed that the 89 Japanese isolates belonged to the
      clade of eight species, according to the molecular phylogenetic analysis. The
      germination rates of isolates belonging to the M. brunneum and M. flavoviride
      var. pemphigi clades were higher at lower temperatures (9.7-11.0 degrees C) and
      lower at higher temperatures (34.3-35.2 degrees C) compared with the other six
      species. The isolates of these two species originated from different geographical
      regions in Japan, despite their uniform germination characteristics. This study
      detected the clear interspecific differences in the in vitro germination
      characteristics of the Japanese isolates of Metarhizium spp. at two different
      temperature regimes. SIGNIFICANCE AND IMPACT OF THE STUDY: The relationships
      between the growth characteristics and phylogenetic placements have not been
      adequately investigated in species of the entomopathogenic fungus Metarhizium.
      This study determined the relationships between the germination rates in hot and
      cold conditions and the phylogenetic placements of 89 Japanese soil isolates of
      Metarhizium spp. Fourteen isolates each of M. brunneum and M. flavoviride var.
      pemphigi, identified by molecular phylogenetic analysis, showed relatively high
      germination rates at lower temperatures and low germination rates at higher
      temperatures compared with isolates, which were identified as six other species.
      This study detected a strong relationship between the phylogenetic placements of
      Japanese Metarhizium spp. isolates and their in vitro germination
      characteristics.

PMID- 24033364
TI  - Upregulated autocrine vascular endothelial growth factor (VEGF)/VEGF receptor-2
      loop prevents apoptosis in haemangioma-derived endothelial cells.
AB  - BACKGROUND: The autocrine vascular endothelial growth factor (VEGF)/VEGF receptor
      (VEGFR)-2 loop is required to maintain the transformed phenotype of many tumours,
      in part, by preventing apoptotic cell death in response to many different
      stimuli. However, it is unclear whether constitutive VEGF/VEGFR-2 activation in
      haemangioma-derived endothelial cells (HaemECs) can lead to a general suppression
      of apoptosis. OBJECTIVES: The objective of this study was to investigate whether
      the autocrine VEGF loop promotes HaemEC survival via its receptor, VEGFR-2.
      METHODS: HaemECs and human umbilical vein endothelial cells (HUVECs) were serum
      starved for 12-48 h. Cell apoptosis was measured. The potential mechanisms of
      VEGF/VEGFR-2-induced HaemEC survival were investigated, and the role of the
      autocrine VEGF/VEGFR-2 loop in preventing propranolol-induced apoptotic HaemEC
      death was also analysed. RESULTS: Compared with HUVECs, HaemECs showed increased
      resistance to apoptosis induced by serum starvation. Upregulated VEGF/VEGFR-2
      signalling in HaemECs induced an autocrine signalling loop, which resulted in Akt
      activation. Furthermore, this activation of Akt was necessary for VEGF/VEGFR-2
      induced protection against serum deprivation-induced HaemEC apoptosis. In
      addition, Bcl-2, which functions as an anti-apoptotic factor and direct
      downstream target of PI3K/Akt, was decreased by the inhibition of VEGF/VEGFR-2,
      which led to an increase in caspase-3 activity, caspase-9 activity and HaemEC
      apoptosis. Moreover, HaemECs acquired greater resistance to propranolol treatment
      than HUVECs, whereas inhibition of VEGF/VEGFR-2 signalling in HaemECs sensitized
      these cells to propranolol-induced apoptosis. CONCLUSIONS: Our results
      demonstrate that upregulation of the autocrine VEGF/VEGFR-2 loop can induce
      general resistance to apoptotic stimuli in HaemECs.

PMID- 24033365
TI  - Expression of miR-155 and miR-126 in situ in cutaneous T-cell lymphoma.
AB  - Recently, miR-155 has been implicated in cutaneous T-cell lymphoma (CTCL). Thus,
      elevated levels of miR-155 were observed in skin lesions from CTCL patients as
      judged from qPCR and micro-array analysis and aberrant, high miR-155 expression
      was associated with severe disease. Moreover, miR-155 promoted proliferation of
      malignant T cells in vitro. Little is, however, known about which cell types
      express miR-155 in vivo in CTCL skin lesions. Here, we study miR-155 expression
      using in situ hybridization (ISH) with a miR-155 probe, a negative control
      (scrambled), and a miR-126 probe as a positive control in nine patients with
      mycosis fungoides, the most frequent subtype of CTCL. We provide evidence that
      both malignant and non-malignant T cells stain weakly to moderately positive with
      the miR-155 probe, but generally negative with the miR-126 and negative control
      probes. Reversely, endothelial cells stain positive for miR-126 and negative for
      miR-155 and the control probe. Solitary T cells with a malignant morphology
      display brighter staining with the miR-155 probe. Taken together, our findings
      suggest that both malignant and non-malignant T cells express miR-155 in situ in
      CTCL. Moreover, they indicate heterogeneity in miR-155 expression among malignant
      T cells. 

PMID- 24033366
TI  - Pre-, peri-, and postoperative oral administration of branched-chain amino acids
      for primary liver cancer patients for hepatic resection: a systematic review.
AB  - Pre-, peri-, and postoperative oral administration of branched-chain amino acids
      (BCAA) to patients with primary liver cancer (PLC) during hepatic resection (HR)
      remains controversial. The aim of this systematic review was to evaluate the
      efficacy and safety of this practice. Seven literature databases were
      systematically searched for randomized controlled trials (RCTs) that reported pre
      , peri-, and postoperative oral administration of BCAA for PLC patients during
      HR. Three RCTs were included in a meta-analysis in which risk ratios (RRs) and
      95% confidence intervals (95% CIs) were calculated. The 2 groups showed similar
      recurrence rates (RR = 1.03, 95% CI 0.78 to 1.36) and similar overall survival
      (RR = 0.91, 95% CI 0.71 to 1.18). Adverse events related to oral administration
      of BCAA were more than the control group, including nausea, vomiting, diarrhea,
      abdominal distension, abdominal pain, and hypertension. However, all adverse
      reactions disappeared after symptomatic treatment. The available evidence
      suggests that although pre-, peri-, and postoperative oral BCAA for patients with
      PLC is safe, it is of questionable clinical value. More RCTs are warranted to
      explore this question definitively. 

PMID- 24033367
TI  - Early transcriptional responses to mercury: a role for ethylene in mercury
      induced stress.
AB  - Understanding the cellular mechanisms of plant tolerance to mercury (Hg) is
      important for developing phytoremediation strategies of Hg-contaminated soils.
      The early responses of alfalfa (Medicago sativa) seedlings to Hg were studied
      using transcriptomics analysis. A Medicago truncatula microarray was hybridized
      with high-quality root RNA from M. sativa treated with 3 MUM Hg for 3, 6 and 24
      h. The transcriptional pattern data were complementary to the measurements of
      root growth inhibition, lipid peroxidation, hydrogen peroxide (H2 O2 )
      accumulation and NADPH-oxidase activity as stress indexes. Of 559 differentially
      expressed genes (DEGs), 91% were up-regulated. The majority of DEGs were shared
      between the 3 and 6 h (60%) time points, including the 'stress', 'secondary
      metabolism' and 'hormone metabolism' functional categories. Genes from ethylene
      metabolism and signalling were highly represented, suggesting that this
      phytohormone may be relevant for metal perception and homeostasis. Ethylene
      insensitive alfalfa seedlings preincubated with the ethylene signalling inhibitor
      1-methylcyclopronene and Arabidopsis thaliana ein2-5 mutants confirmed that
      ethylene participates in the early perception of Hg stress. It modulates root
      growth inhibition, NADPH-oxidase activity and Hg-induced apoplastic H2 O2
      accumulation. Therefore, ethylene signalling attenuation could be useful in
      future phytotechnological applications to ameliorate stress symptoms in Hg
      polluted plants.

PMID- 24033368
TI  - A curious case of the World Health Organization's (WHO) approach on alcohol use
      disorders--inferences from the WHO list of essential drugs.

PMID- 24033369
TI  - Current management of left ventricular assist device erosion.
AB  - Left ventricular assist device (LVAD) pocket infection is a serious and
      potentially fatal complication. Not infrequently, the device erodes externally
      through the thoracoabdominal wall or internally into the peritoneum. In this
      article, we report two cases to illustrate the presentation and challenges
      associated with management of LVAD-pocket infection and wound necrosis.
      Afterward, we review the current therapeutic strategies for LVAD erosion.

PMID- 24033370
TI  - Functional analyses of three ASMT gene family members in rice plants.
AB  - N-acetylserotonin methyltransferase (ASMT) is the final enzyme in a biosynthetic
      pathway that produces melatonin. ASMT may play a rate-limiting role in the
      production of this bioactive molecule in plants. There are three ASMT genes
      (ASMT1-ASMT3) in the rice genome, but only ASMT1 has been functionally
      characterized. A major barrier to further progress in characterizing these genes
      has been a failure of functional expression within the Escherichia coli. Purified
      recombinant ASMT2 and ASMT3 are inactive in ASMT enzyme catalysis. To determine
      the biological functions of ASMT2 and ASMT3, we first overexpressed them in rice
      calli, which resulted in enhanced production of melatonin in the respective
      transgenic calli. To further corroborate the functions of ASMT2 and ASMT3 as ASMT
      genes, we generated stable transgenic rice plants. ASMT enzyme activity was
      increased in comparison with the wild type in T2 homozygous transgenic rice
      plants expressing three ASMT genes independently. When seedlings were treated
      with 1 mm N-acetylserotonin (NAS), leaf melatonin contents were higher in the
      three transgenic lines than in the wild type. There were no significant
      differences between the transgenic lines and the wild type without this
      treatment. ASMT1 and ASMT2 transcripts were highly expressed in stems and
      flowers, but ASMT3 was barely detectable in any of the plant organs. All three
      ASMT mRNAs were simultaneously induced in treatments with abscisic and methyl
      jasmonic acids. 

PMID- 24033371
TI  - Predictive model of avian electrocution risk on overhead power lines.
AB  - Electrocution on overhead power structures negatively affects avian populations
      in diverse ecosystems worldwide, contributes to the endangerment of raptor
      populations in Europe and Africa, and is a major driver of legal action against
      electric utilities in North America. We investigated factors associated with
      avian electrocutions so poles that are likely to electrocute a bird can be
      identified and retrofitted prior to causing avian mortality. We used historical
      data from southern California to identify patterns of avian electrocution by
      voltage, month, and year to identify species most often killed by electrocution
      in our study area and to develop a predictive model that compared poles where an
      avian electrocution was known to have occurred (electrocution poles) with poles
      where no known electrocution occurred (comparison poles). We chose variables that
      could be quantified by personnel with little training in ornithology or electric
      systems. Electrocutions were more common at distribution voltages (<= 33 kV) and
      during breeding seasons and were more commonly reported after a retrofitting
      program began. Red-tailed Hawks (Buteo jamaicensis) (n = 265) and American Crows
      (Corvus brachyrhynchos) (n = 258) were the most commonly electrocuted species. In
      the predictive model, 4 of 14 candidate variables were required to distinguish
      electrocution poles from comparison poles: number of jumpers (short wires
      connecting energized equipment), number of primary conductors, presence of
      grounding, and presence of unforested unpaved areas as the dominant nearby land
      cover. When tested against a sample of poles not used to build the model, our
      model distributed poles relatively normally across electrocution-risk values and
      identified the average risk as higher for electrocution poles relative to
      comparison poles. Our model can be used to reduce avian electrocutions through
      proactive identification and targeting of high-risk poles for retrofitting.

PMID- 24033372
TI  - Increased CD5-positive polyclonal B cells in Castleman disease: a diagnostic
      pitfall.

PMID- 24033373
TI  - Interference between active implanted medical devices and electromagnetic field
      emitting devices is rare but real: results of an incidence study in a population
      of physicians in France.
AB  - BACKGROUND AND OBJECTIVE: Assessing the behavior of active implanted medical
      devices (AIMDs) in response to electromagnetic field (EMF) transmitters is a
      current issue of great importance. Given the numerous telecommunication systems
      and our lack of knowledge as to the impact of electromagnetic effects, this study
      investigated the reality of possible AIMD disturbance by EMFs by interviewing
      health professionals. METHOD: A self-administered postal questionnaire was sent
      to almost 5,000 physicians in five specialties: cardiology; endocrinology; ears,
      nose, and throat; urology; and neurology. It collected data on the existence and
      annual number of incidents observed and the conditions under which they occurred,
      the EMF sources involved, and the means of managing the malfunctions. RESULTS: A
      total of 1,188 physicians agreed to participate. Sixteen percent of participants
      reported cases of implant failure, three-quarters of whom, mainly in cardiology,
      reported rates of at least one incident per year-amounting to more than 100
      incidents per year in all. Severity appeared to be moderate (discomfort or
      transient symptoms), but frequently required resetting or, more rarely, replacing
      the device. Some serious incidents were, however, reported. The sources
      implicated were basically of two types: electronic security systems (antitheft
      and airport gates) and medical electromagnetic radiation devices. These incidents
      were poorly reported within the public health system, preventing follow-up and
      effective performance of alert and surveillance functions. CONCLUSION: Although
      minor, the risk of interference between EMF sources and AIMDs is real and calls
      for vigilance. It particularly concerns antitheft and airport security gates,
      though other sources may also cause incidents.

PMID- 24033374
TI  - More protected vibrational states at the dissociation limit of SCCl2.
AB  - Local vibrational coupling models predict that intramolecular vibrational energy
      redistribution (IVR) is not completely statistical even at the dissociation limit
      of polyatomic molecules. Thus states protected from IVR and from rapid
      dissociation form regular progressions and can be assigned vibrational quantum
      numbers. We previously observed such regular progressions of states in
      vibrational spectra of the molecule SCCl2, but a discrepancy in the density of
      such states remained between theory and experiment. Here we show that the gap can
      be closed by observing and assigning additional vibrational transitions above the
      dissociation limit of SCCl2, and by carefully analyzing the theoretically
      expected density of protected states. The newly observed transitions originate
      from recently assigned and more highly excited vibrational levels in the B
      electronic state, connecting to the X ground state by different Franck-Condon
      factors. Based on our analysis of Franck-Condon activity, we conclude that theory
      and experiment agree within measurement uncertainty. Consistency between theory
      and experiment implies that even more protected states should be observed for
      larger molecules, leading to nonstatistical dissociation reactions. 

PMID- 24033375
TI  - Transanal colorectal resection using natural orifice translumenal endoscopic
      surgery (NOTES).
AB  - The surgical management of rectal cancer has evolved over the past century, with
      total mesorectal excision (TME) emerging as standard of care. As a result of the
      morbidity associated with open TME, minimally invasive techniques have become
      popular. Natural orifice translumenal endoscopic surgery (NOTES) has been held as
      the next revolution in surgical techniques, offering the possibility of
      'incisionless' TME. Early clinical series of transanal TME with laparoscopic
      assistance (n = 72) are promising, with overall intraoperative and postoperative
      complication rates of 8.3% and 27.8%, respectively, similar to laparoscopic TME.
      The mesorectal specimen was intact in all patients, and 94.4% had negative
      margins. There was no oncological recurrence in average-risk patients at short
      term follow up, and 2-year survival rates in high-risk patients were comparable
      to that after laparoscopic TME. These preliminary studies demonstrate transanal
      NOTES TME with laparoscopic assistance to be clinically feasible and safe given
      careful patient selection, surgical expertise, and appropriate procedural
      training. We are hopeful that with optimization of transanal instruments and
      surgical techniques, pure transanal NOTES TME will become a viable alternative to
      open and laparoscopic TME in the future.

PMID- 24033376
TI  - Age-induced hair greying - the multiple effects of oxidative stress.
AB  - An obvious sign of ageing is hair greying, or the loss of pigment production and
      deposition within the hair shafts. Numerous mechanisms, acting at different
      levels and follicular locations, contribute to hair greying, ranging from
      melanocyte stem cells defects to follicular melanocyte death. One key issue that
      is in common to these processes is oxidative damage. At the hair follicle stem
      cells niche, oxidative stress, accelerated by B-cell lymphoma 2 gene (BCL-2)
      depletion, leads to selective apoptosis and diminution of melanocyte stem cells,
      reducing the repopulation of newly formed anagen follicles. Melanotic bulbar
      melanocytes express high levels of BCL-2 to enable survival from melanogenesis-
      and ultraviolet A (UVA)-induced reactive oxygen species (ROS) attacks. With
      ageing, the bulbar melanocyte expression of anti-oxidant proteins such as BCL-2,
      and possibly TRP-2, is reduced, and the dedicated enzymatic anti-oxidant defence
      system throughout the follicle weakens, resulting in enhanced oxidative stress. A
      marked reduction in catalase expression and activity results in millimolar
      accumulation of hydrogen peroxide, contributing to bulbar melanocyte malfunction
      and death. Interestingly, amelanotic melanocytes at the outer root sheath (ORS)
      are somewhat less affected by these processes and survive for longer time even
      within the white, ageing hair follicles. Better understanding of the overtime
      susceptibility of melanocytes to oxidative stress at the different follicular
      locations might yield clues to possible therapies for the prevention and reversal
      of hair greying. 

PMID- 24033377
TI  - Suppressive effect of mangosteen rind extract on the spontaneous development of
      atopic dermatitis in NC/Tnd mice.
AB  - Atopic dermatitis (AD) is a chronic and relapsing skin disorder characterized by
      pruritic and dry skin lesions with allergic inflammation. Recent studies have
      revealed anti-inflammatory and anti-allergic effects of xanthones in mangosteen
      through regulation of the nuclear factor (NF)-kappaB signaling pathway.
      Activation of NF-kappaB signals is responsible for allergic inflammation in AD.
      To develop a new preventive therapy for AD, we examined the effects of the
      natural medicine, mangosteen rind extract (ME), on AD in a murine model. ME (250
      mg/kg per day) was administrated to NC/Tnd mice, a model for human AD, for 6
      weeks to evaluate its preventive effects on AD. We also confirmed the effects of
      ME on various immune cell functions. Oral administration of ME prevented the
      increase of clinical skin severity scores, plasma total immunoglobulin E levels,
      scratching behavior, transepidermal water loss and epidermal hyperplasia in
      NC/Tnd mice; moreover, no adverse effects were noted. We demonstrated that ME
      suppressed thymic stromal lymphopoietin and interferon-gamma mRNA expression both
      in vitro and in vivo. Not only immunoglobulin E production from splenic B cells
      but also immunoglobulin E-mediated degranulation of bone marrow-derived cultured
      mast cells was significantly reduced by the addition of ME to the culture. In
      addition, mRNA expression levels of nerve growth factor were decreased in ME
      administrated NC/Tnd mice compared with those of controls. Keratinocyte
      proliferation was well-controlled by ME application. Oral administration of ME
      exhibited its suppressive potential on the early development of AD by controlling
      inflammation, itch and epidermal barrier function.

PMID- 24033378
TI  - Biomechanical comparison of four technique for pelvic flexure enterotomy closure
      in horses.
AB  - OBJECTIVE: To compare 4 techniques for pelvic flexure enterotomy closure in
      horses. STUDY DESIGN: Ex-vivo study. SAMPLE POPULATION: Cadaveric ascending colon
      specimens (n = 48 horses). METHODS: Pelvic flexure enterotomies of different
      lengths (5 cm, 10 cm) were performed and closed with 1 of 4 techniques: handsewn
      2 layer (HS2); handsewn 1 layer (HS1); skin staples (SKS); or TA90 stapling
      device (TA90). Time to close each enterotomy, bursting pressure, luminal
      reduction, and cost were calculated and compared. RESULTS: HS2 was significantly
      more time consuming to perform in the 5 cm group whereas in the 10 cm group, only
      the HS1 and SKS were faster than the other techniques. Luminal reduction was not
      different between techniques in either group. HS2 resulted in consistently higher
      bursting pressure compared with SKS and TA90 in the 5 cm group and compared to
      all other techniques in the 10 cm group. CONCLUSION: The TA90 technique had the
      lowest bursting pressure and highest cost. The HS2 technique was strongest.

PMID- 24033379
TI  - Great expectations-defining quality in pediatric sedation: outcomes of a
      multidisciplinary consensus conference.
AB  - PURPOSE: Recognizing the inconsistencies in sedation practices, the Society for
      Pediatric Sedation convened this meeting to begin the process of defining quality
      as it relates to the field of pediatric sedation. SCOPE: Millions of procedures
      are performed each year on children. Caring for children, even for routine
      procedures, can be challenging. Children may not have the ability to follow
      commands, tolerate painful stimuli, or even lie still for a diagnostic study.
      Therefore, pharmacologic sedation with medications designed to blunt the
      awareness of the patient and provide relief of pain and anxiety is necessary.
      METHODS: A multidisciplinary group of sedation providers and quality methodology
      experts met in November 2011. Through 2 days of didactics, small workgroups, and
      consensus discussions, the attendees met the objectives of exploring quality in
      pediatric sedation around the Institute of Medicine's () six aims of quality:
      Safe, Effective, Patient Centered, Timely, Efficient, and Equitable. RESULTS: The
      conference findings outlined in this document address the Agency for Healthcare
      Research and Quality's (AHRQ) mission of improving quality healthcare for all
      Americans, especially for underrepresented groups such as children. The
      conference outlines a key next step in defining and achieving quality in
      pediatric procedural sedation.

PMID- 24033380
TI  - Renal allograft outcomes following early corticosteroid withdrawal in Hispanic
      transplant recipients.
AB  - BACKGROUND: Renal transplant outcomes in Hispanics have been conflicting
      regarding acute rejection (AR) and allograft survival. Additionally, the
      feasibility of early corticosteroid withdrawal (ECW) regimens among Hispanics has
      not been adequately addressed. The purpose of this study is to report outcomes
      following ECW among Hispanic renal transplant recipients. METHODS: We
      retrospectively reviewed 498 consecutive renal transplants performed at our
      institution between July 2005 and October 2007, including 73 Hispanic and 146
      white recipients who had ECW (median follow-up 49 months). Demographics,
      transplant data, and outcomes of Hispanic and white recipients (WR) were
      analyzed. RESULTS: Hispanics had a higher incidence of diabetes mellitus and
      hypertension (p = 0.007), a higher proportion of blood type O (p = 0.006), and a
      higher serum panel reactive antibody at the time of transplantation (p = 0.02)
      compared with WR. Additionally, Hispanics were on dialysis longer than WR prior
      to transplantation (p = 0.03). Nevertheless, the incidence of AR, patient, and
      graft survival rates was similar (p > 0.05) between Hispanics and WR. Ethnicity
      was not an independent predictor of inferior patient and graft outcomes in
      multivariate analyses. CONCLUSION: Our single-center experience indicates that
      ECW can be performed in Hispanic renal transplant recipients, with patient and
      allograft outcomes comparable with those observed in WR.

PMID- 24033381
TI  - Effects of interocclusal distance on bite force and masseter EMG in healthy
      participants.
AB  - The aim of this study was to investigate effects of interocclusal distance (IOD)
      on bite force and masseter electromyographic (EMG) activity during different
      isometric contraction tasks. Thirty-one healthy participants (14 women and 17
      men, 21.2 +/- 1.8 years) were recruited. Maximal Voluntary Occlusal Bite Force
      (MVOBF) between the first molars and masseter EMG activity during all the
      isometric-biting tasks were measured. The participants were asked to bite at
      submaximal levels of 20%, 40%, 60% and 80% MVOBF with the use of visual feedback.
      The thickness of the force transducer was set at 8, 12, 16 and 20 mm (= IOD), and
      sides were tested in random sequence. MVOBF was significantly higher at 8 mm
      compared with all other IODs (P < 0.001). Only in women, IOD always had
      significant influence on the corresponding root-mean-square (RMS) value of EMG (P
      < 0.011). When biting was performed on the ipsilateral side to the dominant hand,
      the working side consistently showed higher masseter EMG activity compared with
      the balancing side (P < 0.020). On the contralateral side, there was no
      difference between the masseter EMG at any IODs. The results replicated the
      finding that higher occlusal forces can be generated between the first molars at
      shorter IODs. The new finding in this study was that an effect of hand dominance
      could be found on masseter muscle activity during isometric biting. This may
      suggest that there can be a general dominant side effect on human jaw muscles
      possibly reflecting differences in motor unit recruitment strategies. 

PMID- 24033382
TI  - Impulsivity in inpatient substance abusers: an exploratory study.

PMID- 24033383
TI  - Impact of CYP3A5 genetic polymorphisms on the pharmacokinetics and short-term
      remission in patients with ulcerative colitis treated with tacrolimus.
AB  - BACKGROUND AND AIM: The pharmacokinetics of tacrolimus (Tac) differ among
      individuals, and genetic polymorphisms of cytochrome P-450 (CYP) 3A4, CYP3A5, and
      ABCB1 are thought to be involved. The aim of this study was to clarify whether
      these genetic polymorphisms affect the pharmacokinetics of Tac in patients with
      ulcerative colitis. METHODS: The subjects in this study were 45 patients with
      moderate-to-severe ulcerative colitis who were resistant to other therapies and
      were treated with Tac. The subjects were tested for genetic polymorphisms of
      CYP3A4, CYP3A5, and ABCB1, and the relationship between Tac pharmacokinetics and
      the remission rate was investigated. RESULTS: Of the 45 subjects, 24 (53.3%) were
      CYP3A5 expressers (Exp), and 21 (46.7%) were non-expressers (Non-Exp). The trough
      level and the dose-adjusted trough level on days 2-5 were significantly higher in
      the Non-Exp group than in the Exp group (10.16 +/- 5.84 vs 4.47 +/- 2.50 ng/mL, P
      < 0.0001, 139.36 +/- 77.43 vs 61.37 +/- 41.55 ng/mL per mg/kg/day, P < 0.0001).
      The percentage of patients achieving the optimal trough level on days 2-5 was
      significantly higher in the Non-Exp group than in the Exp group (40.0% vs 4.3%, P
      = 0.01). This trend was also observed on days 7-10. On multivariate analysis,
      factors associated with achievement of the optimal trough level were food non
      intake and Non-Exp of CYP3A5. The remission rate was significantly higher in the
      Non-Exp group than in the Exp group (47.6% vs 16.7%, P = 0.046). CONCLUSIONS:
      CYP3A5 genetic polymorphisms affected the pharmacokinetics of Tac, so that the
      short-term clinical remission rate was different between Exp and Non-Exp of
      CYP3A5.

PMID- 24033384
TI  - Unusual forms of alopecia areata in a Trichology Unit.
AB  - BACKGROUND: Alopecia areata (AA) occurs with the apparition of asyntomatic non
      inflamatory alopecia plaques without scars. We distinguish several variants which
      are divided into two groups: typical forms (AA in single or multiple plaques) and
      atypical forms (by its presentation, evolution or paradoxical regrowth).
      OBJETIVES AND METHODS: We describe the cases of AA treated in our Trichology Unit
      between January 2000 and December 2011. RESULTS: We obtained 488 cases of AA. 114
      (23.36%) were unusual form of AA or had paradoxical regrowth. The most common
      unusual form of AA was sisaipho type (7.37%), followed by AA for black and blonde
      hair (5.32%), atypical diffuse forms (4.30%), androgenetic alopecia type and
      (3.89%) and AA rectangular occipital (0.68%). Furthermore, we found nine cases of
      paradoxical regrowth (1.84%). CONCLUSIONS: Atypical variants of AA in our series
      are less than 25% of all cases, although it should be noted that since it is a
      specialized unit, we may be making a selection bias to be more difficult to
      diagnose cases or poor outcome.

PMID- 24033385
TI  - In Darwinian evolution, feedback from natural selection leads to biased
      mutations.
AB  - Natural selection provides feedback through which information about the
      environment and its recurring challenges is captured, inherited, and accumulated
      within genomes in the form of variations that contribute to survival. The
      variation upon which natural selection acts is generally described as "random."
      Yet evidence has been mounting for decades, from such phenomena as mutation
      hotspots, horizontal gene transfer, and highly mutable repetitive sequences, that
      variation is far from the simplifying idealization of random processes as white
      (uniform in space and time and independent of the environment or context).  This
      paper focuses on what is known about the generation and control of mutational
      variation, emphasizing that it is not uniform across the genome or in time, not
      unstructured with respect to survival, and is neither memoryless nor independent
      of the (also far from white) environment. We suggest that, as opposed to
      frequentist methods, Bayesian analysis could capture the evolution of nonuniform
      probabilities of distinct classes of mutation, and argue not only that the
      locations, styles, and timing of real mutations are not correctly modeled as
      generated by a white noise random process, but that such a process would be
      inconsistent with evolutionary theory. 

PMID- 24033387
TI  - Treatment of shelter cats with oral terbinafine and concurrent lime sulphur
      rinses.
AB  - BACKGROUND: Dermatophytosis is an important contagious and infectious skin
      disease in an animal shelter. Itraconazole is the commonly used systemic
      antifungal drug, but it is expensive in some countries and, at times, difficult
      to obtain. Terbinafine is a fungicidal allylamine with documented in vitro and in
      vivo efficacy against Microsporum canis in pet cats and in cats with experimental
      infections. HYPOTHESIS/OBJECTIVES: To describe the use of oral terbinafine for
      the treatment of M. canis dermatophytosis in shelter cats. METHODS: The response
      to treatment of 85 shelter cats with naturally occurring M. canis dermatophytosis
      was monitored by examination, weekly toothbrush fungal cultures and the number of
      colony-forming units on fungal culture plates. Cats were treated with either 14
      (n = 21) or 21 days (n = 64) of terbinafine per os (p.o.) along with concurrent
      twice weekly lime sulphur rinses and daily environmental disinfection. RESULTS:
      Cats treated with 14 days of terbinafine p.o. showed an initial response to
      therapy but by week 6 had relapsed and required rescue therapy with a course of
      itraconazole (10 mg/kg p.o.) to obtain a cure. Cats treated with 21 days of
      terbinafine p.o. showed a response to treatment similar to published reports
      using itraconazole p.o. for 21 days. The mean and median number of days to
      mycological cure was 22.70 (range 13-39). Terbinafine was well tolerated. None of
      the cats developed oral lesions postgrooming of lime sulphur rinses. CLINICAL
      SIGNIFICANCE: Where itraconazole is not available, substitution with terbinafine
      in established protocols may allow shelters to treat cats that otherwise would go
      untreated.

PMID- 24033386
TI  - RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal
      pulmonary vascular smooth muscle cell proliferation.
AB  - OBJECTIVES: Platelet-activating factor (PAF) is produced by pulmonary vascular
      smooth muscle cells (PVSMC). We studied effects of Rho kinase on PAF stimulation
      of PVSMC proliferation in an attempt to understand the role of RhoA/Rho kinase on
      PAF-induced ovine foetal pulmonary vascular remodelling. Our hypothesis is that
      PAF acts through Rho kinase, as one of its downstream signals, to induce arterial
      (SMC-PA) and venous (SMC-PV) cell proliferation in the hypoxic lung environment
      of the foetus, in utero. MATERIALS AND METHODS: Rho kinase and MAPK effects on
      PAF receptor (PAFR)-mediated cell population expansion, and PAFR expression, were
      studied by DNA synthesis, western blot analysis and immunocytochemistry. Effects
      of constructs T19N and G14V on PAF-induced cell proliferation were also
      investigated. RESULTS: Hypoxia increased PVSMC proliferation and Rho kinase
      inhibitors, Y-27632 and Fasudil (HA-1077) as well as MAPK inhibitors PD 98059 and
      SB 203580 attenuated PAF stimulation of cell proliferation. RhoA T19N and G14V
      stimulated cell proliferation, but co-incubation with PAF did not affect
      proliferative effects of the constructs. PAFR protein expression was
      significantly downregulated in both cell types by both Y-27632 and HA-1077, with
      comparable profiles. Also, cells treated with Y-27632 had less PAF receptor
      fluorescence with significant disruption of cell morphology. CONCLUSIONS: Our
      results show that Rho kinase non-specifically modulated PAFR-mediated responses
      by a translational modification of PAFR protein, and suggest that, in vivo,
      activation of Rho kinase by PAF may be a further pathway to sustain PAFR-mediated
      PVSMC proliferation.

PMID- 24033388
TI  - Quadriceps strength and endurance in fibrotic idiopathic interstitial pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Quadriceps muscle dysfunction is an important
      contributor to exercise limitation in chronic obstructive pulmonary disease, but
      little is known about skeletal muscle function and its impact on exercise
      capacity in patients with fibrotic idiopathic interstitial pneumonia (IIP). The
      aim of the study was to compare quadriceps strength and endurance in patients
      with fibrotic IIP and healthy controls, and relate it to exercise capacity.
      METHODS: Quadriceps strength and endurance, as well as respiratory muscle
      strength, and 6-min walk distance were compared among 25 patients with fibrotic
      IIP, forced vital capacity mean (standard deviation) 78.7 (14.0) %predicted,
      carbon monoxide transfer factor 40.3 (10.9) %predicted and 33 age-matched healthy
      controls using non-volitional measures. Quadriceps strength was assessed using
      magnetic femoral nerve stimulation (quadriceps twitch force), and endurance using
      the decay in force in response to repetitive magnetic stimulation of the
      quadriceps over 5 min. RESULTS: Both groups had comparable anthropometrics,
      gender proportion and respiratory muscle strength. Patients were significantly
      weaker than controls; quadriceps twitch force 10.1 (3.0) kg versus 8.0 (2.4) kg
      (P = 0.013). Quadriceps force in response to repetitive magnetic stimulation
      declined significantly more rapidly in patients during the endurance protocol (P
      < 0.001). In controls, there was a significant relationship between 6-min walk
      distance and quadriceps twitch force (r 0.40, P = 0.038), and quadriceps
      endurance (r 0.59, P = 0.016). In patients, only PaO2 and inspiratory muscle
      strength were retained as independent correlates of 6-min walk distance (r(2)  =
      0.3 P = 0.022). CONCLUSIONS: Quadriceps strength and endurance are reduced in
      patients with fibrotic IIP compared with healthy controls, but are less tightly
      correlated with exercise performance.

PMID- 24033389
TI  - Implantable cardioverter defibrillators in electric and magnetic fields of 400 kV
      power lines.
AB  - BACKGROUND: Implantable cardioverter defibrillator (ICD) therapy has increased in
      Western countries. The aim of the study was to investigate the function of ICDs
      using a human-shaped phantom in electric and magnetic fields of 400 kV power
      lines. METHODS: The phantom was used in the following manner: isolated from the
      ground, earthed from a foot, or earthed from a hand. RESULTS: We performed 37 ICD
      tests using 10 different ICD devices. When the electric fields varied from 6.8
      kV/m to 7.5 kV/m (humidity 70.5%) and the magnetic field was 2.0 MUT, one of the
      ICDs tested recorded 258 ventricular beats/min when a simulated heart signal was
      applied to ICD electrodes. When the exposure was 5.1 kV/m, the same ICD had a
      similar disturbance; however, in a 0.9 kV/m field, it worked correctly.
      CONCLUSIONS: Consequently, no effect on ICDs functioning was observed up to 0.9
      kV/m, while anomalous behavior in some conditions was observed when levels
      exceeded 5.1 kV/m; ICD malfunctioning seems possible within 11.5 m from 400 kV
      power lines or in conditions inducing exposures exceeding 5 kV/m. Further
      development of this research field is needed.

PMID- 24033390
TI  - Life history as a predictor of salamander recovery rate from timber harvest in
      southern appalachian forests, USA.
AB  - Forest management often represents a balance between social, economic, and
      ecological objectives. In the eastern United States, numerous studies have
      established that terrestrial salamander populations initially decline in
      abundance following timber harvest, yet the large-scale and long-term
      consequences are relatively unknown. We used count data from terrestrial survey
      points to examine the relation between salamander abundance and historic timber
      harvest while accounting for imperfect detection of individuals. Overall, stream-
      and terrestrial-breeding salamanders appeared to differ by magnitude of
      population decline, rate of population recovery, and extent of recolonization
      from surrounding forest. Specifically, estimated abundance of both species groups
      was positively associated with stand age and recovery rates were predicted to
      increase over time for red-legged salamanders (Plethodon shermani) and decrease
      in stream-breeding species. Abundance of stream-breeding salamanders was
      predicted to reach a peak by 100 years after timber harvest, and the population
      growth rate of red-legged salamanders was predicted to undergo a significant
      increase 100 years after harvest. Estimated abundance of stream-breeding
      salamanders in young forest stands was also negatively associated with the
      distance to adjacent forest, a result that suggests immigration has a role in the
      recovery of these species. Our results indicate that salamander abundance in
      young forest stands may be only modestly lower than in more mature forest but
      that full recovery from timber harvest may take a substantial amount of time and
      that species life history may affect patterns of recovery. Historia de Vida como
      un Vaticinador de la Tasa de Recuperacion de una Salamandra a la Colecta de
      Madera en los Bosques del Sur de los Apalaches, E.U.A. 

PMID- 24033391
TI  - Dual effect of cAMP agonist on ameliorative function of PKA inhibitor in morphine
      dependent mice.
AB  - The present study shows interactive effects of bucladesine (db-cAMP) as a cyclic
      adenosine monophosphate (cAMP) agonist and H-89 as a protein kinase A (PKA)
      inhibitor on naloxone-induced withdrawal signs in morphine-dependent mice.
      Animals were treated subcutaneously with morphine thrice daily with doses
      progressively increased from 50 to 125 mg/kg. A last dose of morphine (50 mg/kg)
      was administered on the 4th day. Several withdrawal signs were precipitated by
      intraperitoneal (i.p.) administration of naloxone (5 mg/kg). Different doses of
      bucladesine (50, 100, 200 nm/mouse) and H-89 (0.05, 0.5, 1, 5 mg/kg) were
      administered (i.p.) 60 min before naloxone injection. In combination groups,
      bucladesine was injected 15 min before H-89 injection. Single administration of H
      89 (0.5, 1, 5 mg/kg) and bucladesine (50, 100 nm/mouse) significantly attenuated
      prominent behavioral signs of morphine withdrawal. Lower doses of bucladesine
      (50, 100 nm/mouse) in combination with H-89 (0.05 mg/kg) increased the inhibitory
      effects of H-89 on withdrawal signs while in high dose (200 nm/mouse) decreased
      the ameliorative function of H-89 (0.05 mg/kg) in morphine-dependent animals. It
      is concluded that H-89 and bucladesine could affect morphine withdrawal syndrome
      via possible interaction with cyclic nucleotide messengering systems, protein
      kinase A signaling pathways, and modified related neurotransmitters. 

PMID- 24033392
TI  - Genital pyoderma gangrenosum: report of two cases and published work review of
      Japanese cases.
AB  - Pyoderma gangrenosum is an ulcerative skin disorder showing characteristic non
      infectious ulcers and affects the lower extremities in approximately 70% of
      cases. Pyoderma gangrenosum is commonly associated with systemic diseases such as
      inflammatory bowel disease, rheumatoid arthritis and hematological malignancies.
      Herein, we report two cases of Japanese patients diagnosed with genital pyoderma
      gangrenosum. Case 1 was a 74-year-old woman without associated systemic
      complications, whose skin lesion resembled a squamous cell carcinoma and was
      limited to the vulva. Case 2 is an 89-year-old man, who suffered from
      myelodysplastic syndrome and acute myeloid leukemia, and presented with penile
      and leg ulcers mimicking pressure sores. Both cases responded well to systemic
      steroids. We review 13 genital pyoderma gangrenosum cases (76.9% male; aged 30-89
      years) from 1996 to 2012 in Japan, including 11 previously reported cases and the
      present study's two cases. Four of the 13 genital pyoderma gangrenosum cases had
      associated systemic diseases and their skin lesions spread to the extragenital
      areas. Eight of the remaining nine genitalia-localized pyoderma gangrenosum cases
      had no associated systemic diseases. In conclusion, genital pyoderma gangrenosum
      is rare and may be misdiagnosed. It should therefore be considered in cases of
      refractory genital ulcers. In addition, genitalia-localized pyoderma gangrenosum
      tends to be without systemic complications.

PMID- 24033393
TI  - Diversity and biological activities of the bacterial community associated with
      the marine sponge Phorbas tenacior (Porifera, Demospongiae).
AB  - The diversity of the cultivable microbiota of the marine sponge Phorbas tenacior
      frequently found in the Mediterranean Sea was investigated, and its potential as
      a source of antimicrobial, antioxidant and antiplasmodial compounds was
      evaluated. The cultivable bacterial community was studied by isolation,
      cultivation and 16S rRNA gene sequencing. Twenty-three bacterial strains were
      isolated and identified in the Proteobacteria (alpha or gamma classes) and
      Actinobacteria phyla. Furthermore, three different bacterial morphotypes
      localized extracellularly within the sponge tissues were revealed by microscopic
      observations. Bacterial strains were assigned to seven different genera, namely
      Vibrio, Photobacterium, Shewanella, Pseudomonas, Ruegeria, Pseudovibrio and
      Citricoccus. The strains affiliated to the same genus were differentiated
      according to their genetic dissimilarities using random amplified polymorphic DNA
      (RAPD) analyses. Eleven bacterial strains were selected for evaluation of their
      bioactivities. Three isolates Pseudovibrio P1Ma4, Vibrio P1MaNal1 and Citricoccus
      P1S7 revealed antimicrobial activity; Citricoccus P1S7 and Vibrio P1MaNal1
      isolates also exhibited antiplasmodial activity, while two Vibrio isolates P1Ma8
      and P1Ma5 displayed antioxidant activity. These data confirmed the importance of
      Proteobacteria and Actinobacteria associated with marine sponges as a reservoir
      of bioactive compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents
      the first report on the diversity of the cultivable bacteria associated with the
      marine sponge Phorbas tenacior, frequently found in the Mediterranean Sea.
      Evaluation of the antiplasmodial, antimicrobial and antioxidant activities of the
      isolates has been investigated and allowed to select bacterial strains,
      confirming the importance of Proteobacteria and Actinobacteria as sources of
      bioactive compounds.

PMID- 24033394
TI  - Inflammatory bowel disease and novel endoscopic technologies.
AB  - Conventional ileocolonoscopy and barium small bowel follow-through are useful
      techniques for assessing the extension and severity of disease in patients with
      inflammatory bowel disease (IBD). More recently, novel techniques to enable IBD
      diagnosis have been developed, such as capsule endoscopy (CE), balloon
      enteroscopy (BE), computed tomography enterography (CTE) and magnetic resonance
      enterography (MRE). The advantages of CE and BE are that they enable mucosal
      assessment directly whereas the usefulness of CTE/MRE is in its ability to enable
      detection of transmural inflammation, stenosis, and extraintestinal lesions
      including abscesses and fistulas. In ulcerative colitis (UC), colitis-associated
      dysplasia/cancer is one of the critical complications in patients with chronic
      disease. Detection of colitis-associated cancer is difficult in cases with
      inflammation. Magnification colonoscopy has been used to detect dysplasia in
      patients with chronic UC. Furthermore, colon CE and endocytoscopy have also
      developed and these might be used for selected patients in the near future.

PMID- 24033395
TI  - Expression of matrix metalloproteinase-13 in odontoblast-like cells.

PMID- 24033396
TI  - Response to Dr. Tjaderhane and Dr. Salo's letter.

PMID- 24033397
TI  - Use of inverse spatial conservation prioritization to avoid biological diversity
      loss outside protected areas.
AB  - Globally expanding human land use sets constantly increasing pressure for
      maintenance of biological diversity and functioning ecosystems. To fight the
      decline of biological diversity, conservation science has broken ground with
      methods such as the operational model of systematic conservation planning (SCP),
      which focuses on design and on-the-ground implementation of conservation areas.
      The most commonly used method in SCP is reserve selection that focuses on the
      spatial design of reserve networks and their expansion. We expanded these methods
      by introducing another form of spatial allocation of conservation effort relevant
      for land-use zoning at the landscape scale that avoids negative ecological
      effects of human land use outside protected areas. We call our method inverse
      spatial conservation prioritization. It can be used to identify areas suitable
      for economic development while simultaneously limiting total ecological and
      environmental effects of that development at the landscape level by identifying
      areas with highest economic but lowest ecological value. Our method is not based
      on a priori targets, and as such it is applicable to cases where the effects of
      land use on, for example, individual species or ecosystem types are relatively
      small and would not lead to violation of regional or national conservation
      targets. We applied our method to land-use allocation to peat mining. Our method
      identified a combination of profitable production areas that provides the needed
      area for peat production while retaining most of the landscape-level ecological
      value of the ecosystem. The results of this inverse spatial conservation
      prioritization are being used in land-use zoning in the province of Central
      Finland. 

PMID- 24033398
TI  - Effects of astaxanthin and esterified glucomannan on hematological and serum
      parameters, and liver pathological changes in broilers fed aflatoxin-B1
      contaminated feed.
AB  - The effects of astaxanthin (ASTA) and esterified glucomannan (EMG) on
      hematological and serum parameters, and liver pathological changes in broilers
      fed on aflatoxin-B1 (AFB1) contaminated diet were investigated. Two hundred and
      forty 10-day-old broilers were randomly assigned to one of five dietary
      treatments including: (i) control diet; (ii) AFB1-contaminated diet; (iii) AFB1 +
      EGM diet; (iv) AFB1 + ASTA diet; and (v) AFB1 + EGM + ASTA diet. At 35 days old,
      blood and liver tissue samples were collected for analysis. Results indicated
      that total white blood cell (WBC) number, hemoglobin (Hgb) concentration,
      hematocrit (Hct) level, serum alanine amino transferase (AST) and gamma-glutamyl
      transferase (GGT) activities, red blood cell (RBC) number, serum globulin (GLB)
      and urea nitrogen (BUN) concentrations (P < 0.05) were increased by feeding AFB1
      contaminated diet. EMG and ASTA alleviated the alteration of RBC, WBC, Hgb and
      AST caused by AFB1-contaminated diet. Liver superoxide dismutase (SOD) activity
      was reduced, while myeloperoxidase (MPO) activity was increased by AFB1
      contaminated diet (P < 0.05). Both EGM and ASTA restrained the increase of MPO
      activity (P < 0.05). Degeneration of the liver tissues was found in broilers fed
      AFB1-contaminated diet. It suggested that feeding 0.4 mg/kg AFB1-contaminated
      diet resulted in adverse effects on blood parameters and liver morphology.
      Dietary addition of EGM addition at 5 g/kg diet, ASTA at 10 mg/kg diet and
      especially their combination showed positive protection effects on alleviating
      the alteration of feeding AFB1. The results indicated that supplementation of 5 g
      EGM/kg diet, 10 mg ASTA/kg diet and their combination could partially or greatly
      alleviate the adverse effects caused by AFB1, with the EGM+ASTA group receiving
      the most effective treatment. 

PMID- 24033399
TI  - Isolation and characterization of chitin-degrading micro-organisms from the
      faeces of Goeldi's monkey, Callimico goeldii.
AB  - AIMS: The objective of this study was the isolation and characterization of
      chitin-degrading micro-organisms from the faeces of the insectivorous Goeldi's
      monkey, Callimico goeldii. METHODS AND RESULTS: Faeces samples were screened for
      chitin-degrading bacteria using basal medium in which chitin was included as the
      carbon and energy source. Of fifteen bacterial isolates with chitin-degrading
      activity, fourteen were also capable of degrading cellulose. All isolates were
      either aerobes or facultative anaerobes. CONCLUSIONS: Phylogenetic analyses of
      those isolates exhibiting strongest activity, as determined by the most
      distinctive zones of clearing in chitin-supplemented medium, were identified as
      Cellulosimicrobium spp., Arthrobacter spp., Staphylococcus spp. and
      Enterobacteriaceae. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports on
      the isolation of chitin-degrading microflora from nonhuman primates. Considering
      that chitin and cellulose are the most abundant naturally occurring polymers, it
      is of interest to note that the majority of isolates are capable of digesting
      both substrates. This may be of significance given that omnivorous primates live
      in seasonal environments, where the availability of food items varies with the
      seasons. Furthermore, given the presence of a chitin-degrading microflora, this
      may have implications, in terms of the inclusion of fungi and/or insects in the
      diets of these animals in captivity, whether as part of medical research or
      conservation programmes.

PMID- 24033400
TI  - Gastric parietal cell vacuolation mimicking gastric carcinoma.

PMID- 24033401
TI  - Liver transplantation in alcoholic patients.

PMID- 24033402
TI  - Improving completion rates for client intake forms through Audio Computer
      Assisted Self-Interview (ACASI): results from a pilot study with the Avon Breast
      Health Outreach Program.
AB  - This study compares rates of completion of client intake forms (CIFs) collected
      via three interview modes: audio computer-assisted self-interview (ACASI), face
      to-face interview (FFI), and self-administered paper-based interview (SAPI). A
      total of 303 clients served through the Avon Breast Health Outreach Program
      (BHOP) were sampled from three U.S. sites. Clients were randomly assigned to
      complete a standard CIF via one of the three interview modes. Logistic regression
      analyses demonstrated that clients were significantly more likely to complete the
      entire CIF via ACASI than either FFI or SAPI. The greatest observed differences
      were between ACASI and SAPI; clients were almost six times more likely to
      complete the CIF via ACASI as opposed to SAPI (AOR = 5.8, p < .001). We recommend
      that where feasible, ACASI be utilized as an effective means of collecting client
      level data in healthcare settings. Adoption of ACASI in health centers may
      translate into higher completion rates of intake forms by clients, as well as
      reduced burden on clinic staff to enter data and review intake forms for
      completion. 

PMID- 24033403
TI  - Hypocalcemia immediately after renal transplantation.
AB  - BACKGROUND: After renal transplantation (RTX), hypercalcemia, mainly due to
      persistent hyperparathyroidism, and hypophosphatemia, caused by the improved
      ability to excrete phosphorus in the renal tubules, are expected. However,
      immediately after RTX, a transient reduction in serum calcium (Ca) levels has
      been previously reported, the reason for which is not clear. PATIENTS AND
      METHODS: In 21 patients receiving ABO compatible living donor kidney transplants,
      serum levels of Ca, phosphorus, intact parathyroid hormone (iPTH), 1,25
      dihydroxyvitamin D, and tacrolimus were measured within three wk after RTX, along
      with urinary Ca and phosphorus excretion. The immunosuppressive regimen consisted
      of a three-drug combination including a glucocorticoid, a calcineurin inhibitor,
      and an antimetabolite agent. RESULTS: Serum Ca levels declined significantly
      during the first post-operative week. Urinary Ca excretion increased immediately
      after RTX and gradually normalized. Increased urinary Ca excretion did not
      correlate with serum levels of iPTH and tacrolimus. CONCLUSIONS: Immediately
      after RTX, regardless of serum iPTH and tacrolimus levels, transient increases in
      urinary Ca excretion and hypocalcemia were observed. Administration of
      glucocorticoids is one potential cause of inappropriate urinary Ca wasting.

PMID- 24033404
TI  - Clinical tools do not predict pathological complete response in patients with
      esophageal squamous cell cancer treated with definitive chemoradiotherapy.
AB  - Chemoradiotherapy for locally advanced esophageal squamous cell carcinoma is
      associated with high rates of pathological complete response. A pathological
      complete response is recognized to be an important predictor of improved
      survival, to the extent that observation rather than surgery is advocated by some
      in patients with presumed pathological complete response based on their clinical
      response. The goal of this study was to look at the ability of clinical variables
      to predict pathological complete response after chemoradiotherapy for locally
      advanced esophageal squamous cell carcinoma. We reviewed retrospectively patients
      with locally advanced esophageal squamous cell carcinoma who underwent
      chemoradiotherapy followed by surgery and compared those with pathological
      complete response to patients with residual disease. Between January 1996 and
      December 2010, 116 patients met inclusion criteria. Fifty-six percent of patients
      had a pathological complete response and a median survival of 128.1 months versus
      28.4 months in patients with residual disease. When compared with patients with
      residual disease, patients with a pathological complete response had a lower post
      neoadjuvant positron emission tomography (PET) maximum standardized uptake value
      (SUVmax), a larger decrease in PET SUVmax, a less thick tumor on post
      chemoradiotherapy computed tomography and a higher rate of normal appearing post
      chemoradiotherapy endoscopy with benign biopsy of the tumor bed. However, none of
      these characteristics alone was able to correctly identify patients with a
      pathological complete response, and none has significant specificity. Although
      the rate of pathological complete response after chemoradiotherapy is high in
      patients with esophageal squamous cell carcinoma, the ability of identifying
      patients with pathological complete response is limited. A reduction of the PET
      SUVmax by >70%, a normal appearing endoscopic examination, and no residual
      disease on biopsy all were seen in >65% of the patients with a pathological
      complete response. Even if these findings were unable to confirm the absence of
      residual disease in the primary tumor, they can help guide expectant management
      in high-risk patients. 

PMID- 24033405
TI  - Dithiocarb (N,N-diethyldithiocarbamate, DEDTC) decreases levels of biogenic
      monoamines in the adult mouse brain.
AB  - AIMS: Dithiocarb (diethyldithiocarbamate, DEDTC) belongs to the group of
      dithiocarbamates and is the main metabolite of disulphiram, a drug of choice for
      the treatment of alcohol dependence. Its therapeutic potential relays on its
      ability to create an unpleasant aversive reaction following the ingestion of
      alcohol, and this effect is usually accompanied by neurobehavioural symptoms.
      Most of these can be attributed to the impaired metabolism of brain biogenic
      amines. METHODS: To gain new insights into the dithiocarbamates and their effects
      on neurotransmitter systems, an in vivo experimental model based on daily
      injections of DEDTC in adult mice for 7 days was established. To this end, the
      concentrations of the three major brain monoamines, dopamine (DA), noradrenaline
      (NA) and serotonin (5-HT) were measured in whole brain extracts with high
      performance liquid chromatography (HPLC). The levels of D2 dopamine receptor
      (D2R) were evaluated by Western blot and by immunohistochemical techniques the
      cell pattern of tyrosine hydroxylase (TH), dopa beta hydroxylase (DBH) and
      choline acetyltransferase ChAT) were analysed. RESULTS: A significant reduction
      in DA and 5-HT levels was observed, whereas NA was not affected. Moreover,
      decreases in D2R levels, as well as in enzymes such as TH, DBH and ChAT, were
      found. CONCLUSIONS: Our data suggest that DEDTC provokes alterations in biogenic
      amines and in different substrates of neurotransmitter systems, which could
      explain some of the neurobehavioural effects observed in patients treated with
      disulphiram.

PMID- 24033406
TI  - Unravelling the genetic complexity of sorghum seedling development under low
      temperature conditions.
AB  - Sorghum is a promising alternative to maize for bioenergy production in Europe;
      however, its use is currently limited by poor adaptation to low temperatures
      during and after germination. We collected multi-trait phenotype data under
      optimal and suboptimal temperatures in a genetically diverse recombinant inbred
      line (RIL) mapping population showing contrasting segregation patterns for pre-
      and post-emergence chilling tolerance. Germination, emergence, seedling
      development, root architecture and seedling survival were assessed in two
      different seedlots. Emergence and root establishment were found to be the key
      determinants of development and survival under chilling stress. Highly
      interactive epistatic quantitative trait loci (QTL) hotspots, including a
      previously unknown QTL on Sb06 with a significant effect on prolonged chilling
      survival, were found to regulate different physiological mechanisms contributing
      to maintenance of growth and development despite the chilling temperatures. The
      major QTL regions harbour promising candidate genes with known roles in abiotic
      stress tolerance. Identification of loci in the QTL hotspot regions conferring
      maintenance of cell division and growth under early chilling stress represents a
      promising step towards breeding for successful establishment of sorghum in
      temperate climates. 

PMID- 24033407
TI  - Recent and future changes in extreme rainfall in the Catskills region of New
      York.
AB  - Recent flooding events in the Catskills such as Tropical Storm Irene have raised
      concerns regarding changes in the frequency of heavy rainfall. The extreme
      precipitation records of four long-term observing sites are analyzed based on two
      measures of heavy rainfall. The number of events that produce >=50.8 mm of
      precipitation per year show little evidence of an increasing trend. Rather, the
      climatology of Catskills stations is marked by considerable year-to-year and
      decade-to-decade variability. Because of this variability, a different measure of
      extreme precipitation, the 100-year storm, attained its highest value in the
      early 1960s. This was an artifact of the reliance of the analysis procedure on a
      relatively short record that coincided with high precipitation. Current
      engineering design for infrastructure affected by extreme rainfall is based on
      this metric. After 1960, the 100-year storm declined, until rising again after
      1990. This rise is consistent with a regional trend toward higher precipitation
      extremes. Climate-model projections show this trend continuing at a rate of 2-3%
      per decade through 2069. The serendipitously high 100-year-storm value computed
      in 1960 may provide some buffer to the expected effects of this change in extreme
      rainfall in the Catskills.

PMID- 24033408
TI  - Irritable bowel syndrome in patients with chronic pruritus of undetermined
      origin.
AB  - BACKGROUND: Chronic pruritus is an important distressing condition that is often
      refractory to treatment. Irritable bowel syndrome (IBS) is a functional
      gastrointestinal disorder that occurs without an organic cause. OBJECTIVES: We
      aimed to investigate the relationship between chronic pruritus of undetermined
      origin (CPUO) and IBS. METHODS: Eighty patients with chronic pruritus (CP) of
      undetermined origin and fifty healthy control subjects without pruritus were
      included into the study. All of the participants were examined by a
      gastroenterologist for concomitant IBS. RESULTS: The frequency of IBS was found
      higher in patients with CP of undetermined origin (P: 0.02), but we did not
      observe any significant association between pruritus intensity and either
      presence of IBS (P: 0.08) or the subtypes of the syndrome (P: 0.40). Furthermore,
      patients with CP of undetermined origin between 40 and 60 years, female gender
      and longer duration of the disease were found to be significantly associated with
      the presence of IBS (P: 0.02, P: 0.01 and P < 0.001). CONCLUSIONS: We found that
      the frequency of IBS was higher in patients with CP than in healthy controls. Our
      study is the first report about the relation between CP of undetermined origin
      and IBS. Further studies with larger numbers of the patients are needed to show
      association between IBS and CPUO using laboratory tests to define underlying
      diseases such as lactose intolerance, functional dyspepsia and emotional
      diseases.

PMID- 24033409
TI  - First report of isolation of Mycobacterium novocastrense from water supplies.
AB  - We herein present the first documented report associated with the isolation of
      Mycobacterium novocastrense from environment. The identification and
      characterization of four unrelated isolates, one from the surface water and the
      other three from hospital water, were achieved by various conventional and
      molecular tests including a genus-specific PCR for Mycobacterium based on 65-kDa
      heat shock protein (hsp) gene and 16S rDNA sequencing. Our findings might shed
      further light on the natural habitat of this rare Mycobacterium.

PMID- 24033410
TI  - Health and safety risks associated with public injecting among people who inject
      drugs in Bangkok, Thailand.
AB  - INTRODUCTION AND AIMS: The injection of illicit drugs in public spaces is known
      to pose significant health risks to people who inject drugs (IDU). However, to
      our knowledge this practice has not been explored in the Asian context.
      Therefore, we sought to characterise the prevalence of and factors associated
      with public injecting among a community-recruited sample of IDU in Bangkok,
      Thailand. DESIGN AND METHODS: Data were derived from the Mitsampan Community
      Research Project between July and October 2011. Using multivariate logistic
      regression, this cross-sectional study examined the prevalence and correlates of
      public injecting within the past six months among 437 IDU participants. RESULTS:
      In total, 121 (27.7%) participants reported injecting drugs in a public space
      within the past six months. In multivariate analyses, public drug injection was
      independently associated with male gender [adjusted odds ratio (AOR) 2.51, 95%
      confidence interval (CI)) 1.29-5.22], weekly heroin injection (AOR 2.19, 95% CI
      1.27-3.77), assisted injection (AOR 1.93, 95% CI 1.06-3.49), rushed injection
      (AOR 4.36, 95% CI 2.65-7.24), incarceration (AOR 2.27, 95% CI 1.01-5.04) and
      noticing police presence where drugs are bought or used (AOR 1.83, 95% CI 1.06
      3.19). DISCUSSION AND CONCLUSION: A substantial proportion of Thai IDU in our
      sample reported recent public drug injection. This behaviour was independently
      associated with a wide range of individual and contextual factors that pose
      significant health and safety risks to the IDU. These findings highlight the
      importance of addressing the broader social and physical risk environment
      surrounding IDU as a means of preventing negative health outcomes among this
      population.

PMID- 24033411
TI  - Life after critical illness: an overview.
AB  - AIMS AND OBJECTIVES: To illustrate the potential physical and psychological
      problems faced by patients after an episode of critical illness, highlight some
      of the interventions that have been tested and identify areas for future
      research. BACKGROUND: Recovery from critical illness is an international problem
      and as an issue is likely to increase. For some, recovery from critical illness
      is prolonged, subject to physical and psychological problems that may negatively
      impact upon health-related quality of life. METHODS: The literature accessed for
      this review includes the work of a number of key researchers in the field of
      critical care research. These were identified from a number of sources include
      (1) personal knowledge of the research field accumulated over the last decade and
      (2) using the search engine 'The Knowledge Network Scotland'. RESULTS: Fatigue
      and weakness are significant problems for critical care survivors and are common
      in patients who have been in ICU for more than one week. Psychological problems
      include anxiety, depression, post-traumatic stress, delirium and cognitive
      impairment. Prevalence of these problems is difficult to establish for a number
      of methodological reasons that include the use of self-report questionnaires, the
      number of different questionnaires used and the variation in administration and
      timing. Certain subgroups of ICU survivors especially those at the more severe
      end of the illness severity spectrum are more at risk and this has been
      demonstrated for both physical and psychological problems. Findings from
      international studies of a range of potential interventions are presented.
      However, establishing effectiveness for most of these still has to be empirically
      demonstrated. CONCLUSION: What seems clear is the need for a co-ordinated,
      multidisciplinary, designated recovery and rehabilitation pathway that begins as
      soon as the patient is admitted into an intensive care unit.

PMID- 24033412
TI  - Risk factor-based interventions or population-based smoking policy initiatives in
      tobacco smoking prevention? A reply to Najman (2013) concerning commentary on
      Lindstrom et al. (2013).

PMID- 24033413
TI  - Hospital-integrated general practice: a promising way to manage walk-in patients
      in emergency departments.
AB  - RATIONALE, AIMS AND OBJECTIVES: The inappropriate use and overcrowding of
      emergency departments (EDs) by walk-in patients are well-known problems in many
      countries. The current study aimed to determine whether ambulatory walk-in
      patients could be treated more efficiently in a new hospital-integrated general
      practice (HGP) for emergency care services compared to a traditional ED. METHODS:
      We conducted a pre-post comparison before and after the implementation of a new
      HGP. Participants were walk-in patients attending the ED of a city hospital in
      Zurich. Main outcome measures were differences in total process time, time
      intervals between stages of care and diagnostic resources used. RESULTS: The
      median process time from admission to discharge was 120 minutes in the ED
      [interquartile range (IQR): 80-165] versus 60 minutes in the HGP (IQR: 40-90) (P
      < 0.001). The adjusted odds ratio of receiving any additional diagnostics was
      1.86 (95% confidence interval 1.06-3.27; P = 0.032) for ED doctors versus general
      practitioners (GPs) when controlling for patients' age, sex and injury-related
      medical problems. CONCLUSION: The HGP is an efficient way to manage walk-in
      patients with regard to process time and utilization of additional diagnostic
      resources. The involvement of GPs in the HGPs should be considered as a promising
      model to overcome the inappropriate use of resources in EDs for walk-in patients
      who can be treated by ambulatory care.

PMID- 24033414
TI  - MicroRNA profile before and after antiviral therapy in liver transplant
      recipients for hepatitis C virus cirrhosis.
AB  - BACKGROUND AND AIM: Management of hepatitis C virus (HCV) recurrence is a major
      challenge after liver transplantation. Significant dysregulated expression of HCV
      receptors (i.e. claudin-1, occludin, tetraspanin CD81, scavenger receptor type
      B1) has been shown recently during HCV infection. This might facilitate
      hepatocytic entry and reinfection of HCV. MicroRNAs (miRs) play role in the
      regulation of gene expression. We aimed to characterize miR expression profiles
      related to HCV infection and antiviral therapy in adult liver transplant
      recipients, with special emphasis on miRs predicted to target HCV receptors.
      METHODS: Twenty-eight adult liver transplant recipients were enrolled in the
      study. Paired biopsies were obtained at the time of HCV recurrence and at the end
      of antiviral treatment. MiRs for HCV receptors were selected using target
      prediction software. Expression levels of miR-21, miR-23a miR-34a, miR-96, miR
      99a*, miR-122, miR-125b, miR-181a-2*, miR-194, miR-195, miR-217, miR-221, and miR
      224 were determined by reverse transcription-quantitative polymerase chain
      reaction. RESULTS: miR-99a* and miR-224 expressions were increased in HCV
      recurrence samples, while miR-21 and miR-194 were decreased in comparison to
      normal liver tissue. Increased expressions of miR-221, miR-224, and miR-217 were
      observed in samples taken after antiviral therapy when compared with HCV
      recurrence samples. High HCV titer at recurrence was associated with higher level
      of miR-122. CONCLUSIONS: Samples at recurrence of HCV and after antiviral therapy
      revealed distinct HCV-related miR expression profiles, with significant
      dysregulation of those miRNAs potentially targeting mRNAs of HCV receptors. In
      particular, miR-194 and miR-21 might be involved in the regulation of HCV
      receptor proteins' expression during HCV infection and antiviral therapy.

PMID- 24033415
TI  - Mechanical compressive force inhibits adipogenesis of adipose stem cells.
AB  - OBJECTIVE: The aim of this study was to investigate effects of mechanical
      compressive force on differentiation of adipose-derived stem cells (ASCs) in
      vitro. MATERIALS AND METHODS: Mice ASCs were treated with compressive force (2000
      MUepsilon, 1 Hz) for 2 or 6 h after adipogenic induction for 3 days, then oil red
      O staining was used to examine oil droplet-filled cells. Adipogenic genes, PPAR
      gamma1 and APN, were examined by real-time PCR and immunofluorescence (IF)
      staining was performed to test expression of de-PPAR-gamma and ph-PPAR-gamma at
      the protein level. RESULTS: Our data showed that mechanical compressive force
      reduced numbers of oil droplet-filled cells, and down-regulated mRNA levels of
      both PPAR-gamma1 and APN and protein level of PPAR-gamma, in ASCs. CONCLUSIONS:
      In culture medium containing adipogenic stimuli, mechanical compressive force
      inhibited adipogenesis of ASCs.

PMID- 24033416
TI  - Proximal and distal gastro-oesophageal reflux in chronic obstructive pulmonary
      disease and bronchiectasis.
AB  - BACKGROUND AND OBJECTIVE: The aims of this observational study were (i) to
      examine the prevalence of symptomatic and clinically silent proximal and distal
      gastro-oesophageal reflux (GOR) in adults with chronic obstructive pulmonary
      disease (COPD) or bronchiectasis, (ii) the presence of gastric aspiration, and
      (iii) to explore the possible clinical significance of this comorbidity in these
      conditions. METHODS: Twenty-seven participants with COPD, 27 with bronchiectasis
      and 17 control subjects completed reflux symptom evaluation and dual-channel 24 h
      oesophageal pH monitoring. In those with lung disease, pepsin levels in sputum
      samples were measured using enzyme-linked immunosorbent assay, with disease
      severity (lung function and high-resolution computed tomography) also measured.
      RESULTS: The prevalence of GOR in COPD was 37%, in bronchiectasis was 40% and in
      control subjects was 18% (P = 0.005). Of those diagnosed with GOR, clinically
      silent reflux was detected in 20% of participants with COPD and 42% with
      bronchiectasis. While pepsin was found in 33% of COPD and 26% of bronchiectasis
      participants, the presence of pepsin in sputum was not related to a diagnosis of
      GOR based on oesophageal pH monitoring in either condition. Neither a diagnosis
      of GOR nor the presence of pepsin was associated with increased severity of lung
      disease in COPD or bronchiectasis. CONCLUSIONS: The prevalence of GOR in COPD or
      bronchiectasis is twice that of the control population, and the diagnosis could
      not be based on symptoms alone. Pepsin was detected in sputum in COPD and
      bronchiectasis, suggesting a possible role of pulmonary aspiration, which
      requires further exploration.

PMID- 24033417
TI  - Response.

PMID- 24033418
TI  - Isolation and partial characterization of a bacteriocin produced by Lactobacillus
      plantarum BM-1 isolated from a traditionally fermented Chinese meat product.
AB  - Lactobacillus plantarum BM-1 isolated from a traditionally fermented Chinese meat
      product was found to produce a novel bacteriocin that is active against a wide
      range of gram-positive and gram-negative bacteria. Production of the bacteriocin
      BM-1 started early in the exponential phase and its maximum activity (5120 AU/mL)
      was recorded early during the stationary phase (16 hr). Bacteriocin BM-1 is
      sensitive to proteolytic enzymes but stable in the pH range of 2.0-10.0 and heat
      resistant (15 min at 121 degrees C). This bacteriocin was purified through pH
      mediated cell adsorption-desorption and cation-exchange chromatography on an SP
      Sepharose Fast Flow column. The molecular weight of the purified bacteriocin BM-1
      was determined to be 4638.142 Da by electrospray ionization Fourier transform
      mass spectrometry. Furthermore, the N-terminal amino acid sequence was obtained
      through automated Edman degradation and found to comprise the following 15 amino
      acid residues: H2 N-Lys-Tyr-Tyr-Gly-Asn-Gly-Val-Tyr-Val-Gly-Lys-His-Ser-Cys-Ser.
      Comparison of this sequence with that of other bacteriocins revealed that
      bacteriocin BM-1 contains the consensus YGNGV amino acid motif near the N
      terminus. Based on its physicochemical characteristics, molecular weight, and N
      terminal amino acid sequence, plantaricin BM-1 is a novel class IIa bacteriocin. 

PMID- 24033419
TI  - Strains of the intestinal spirochaete Brachyspira pilosicoli attach to and
      aggregate erythrocytes.
AB  - The anaerobic intestinal spirochaete Brachyspira pilosicoli colonizes the large
      intestine of various species of mammals and birds, where it may induce colitis.
      Strains of the spirochaete have also been isolated from the bloodstream of
      immunocompromised human patients and have been seen in liver sections, and a
      similar systemic spread was recently observed in experimentally infected
      chickens. Some other spirochaete species that may be present in blood attach to
      and aggregate erythrocytes, and this is believed to contribute to disease
      severity. The aim of the current study was to determine whether B. pilosicoli
      strains have the capacity to attach to and aggregate erythrocytes. Initially,
      four strains of B. pilosicoli were incubated with erythrocytes from sheep, cows,
      pigs, dogs, humans, chickens and geese, and were observed by phase-contrast
      microscopy. Only strain WesB attached, and this was only with erythrocytes from
      chickens and geese. Subsequently, six other strains of B. pilosicoli were tested
      just with goose erythrocytes, and five attached to and caused aggregation of the
      erythrocytes. Scanning and transmission electron microscopy demonstrated that
      spirochaetes abutted and apparently firmly attached to the erythrocyte membranes.
      Aggregation of erythrocytes by B. pilosicoli may contribute to disease severity
      in species that develop a spirochaetaemia. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The intestinal spirochaete Brachyspira pilosicoli has been isolated from the
      bloodstream of immunocompromised human patients, and spread to the liver has been
      reported in humans and in experimentally infected chickens. In this study, B.
      pilosicoli was shown to undergo attachment by one cell end to chicken and goose
      erythrocytes in vitro and to aggregate them. This activity has the potential to
      contribute to disease severity in avian and possibly other species that develop a
      spirochaetaemia and systemic spread. Avian erythrocytes may be useful for
      studying the mechanisms by which B. pilosicoli attaches to cells.

PMID- 24033420
TI  - Migraine-like episodic pain behavior in a dog: can dogs suffer from migraines?
AB  - Migraines and other primary headache disorders commonly affect people. There is
      evidence to suggest that migraines can occur in dogs. In this review, we present
      a dog with paroxysmal episodes that have a striking resemblance to human
      migraine, and we give an overview of migraine in people. The current
      classification, clinical signs, and diagnosis in people are discussed, as well as
      the anatomy of head pain, pathophysiology, pharmacology, and treatment options. 

PMID- 24033421
TI  - Hypercoagulability and ACTH-dependent hyperadrenocorticism in dogs.
AB  - BACKGROUND: Dogs with hyperadrenocorticism are at risk of thromboembolic disease,
      which might be caused by an underlying hypercoagulable state.
      HYPOTHESIS/OBJECTIVES: To assess hemostatic function in dogs with ACTH-dependent
      hyperadrenocorticism (ADHAC) before and after treatment. ANIMALS: Nineteen dogs
      with ADHAC and 40 normal dogs. METHODS: Prospective, observational study. Dogs
      with ADHAC were recruited from the referral hospital patient population; normal
      dogs were recruited from staff and students at the study's institution.
      Hemostasis was assessed before and at 3 and 6 months after treatment with
      trilostane (T0, T3, T6) by kaolin-activated thrombelastography with platelet
      mapping (TEG-PM), prothrombin time, activated partial thromboplastin time,
      fibrinogen concentration, and antithrombin activity (AT). RESULTS: Dogs with
      ADHAC had statistically significantly increased alpha-angle (P < .01) and maximum
      amplitude (MA)(thrombin) (P < .01) on TEG-PM, and significantly decreased kappa
      (P < .005) at T0, T3, and T6. Platelet count (P < .001) and fibrinogen
      concentration (P < .001), but not AT activity, were increased in dogs with ADHAC
      at T0, T3, and T6. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with ADHAC have
      thrombelastographic evidence of hypercoagulability and remained hypercoagulable
      during treatment. AT deficiency does not appear to be involved in the
      pathogenesis of hypercoagulability in this population.

PMID- 24033422
TI  - Evaluation of efficacy of mineral oil, charcoal, and smectite in a rat model of
      equine cantharidin toxicosis.
AB  - BACKGROUND: The efficacy of orally administered therapeutics for the treatment of
      cantharidin intoxication has not been evaluated in controlled studies. OBJECTIVE:
      To develop a model of acute cantharidin intoxication in laboratory rats and to
      evaluate in this model the relative efficacy of 3 gastrointestinal therapies used
      to treat equine cantharidin toxicosis. ANIMALS: Sixty-four male Sprague-Dawley
      rats. METHODS: A blinded, randomized, controlled study was performed on rats
      surgically implanted with telemetry transmitters for evaluating heart rate,
      locomotor activity, and body temperature. Orogastric administration of
      cantharidin was performed within 15 seconds before administration of mineral oil,
      activated charcoal, or smectite. Negative control groups received therapeutic
      agents alone. Urine was collected for cantharidin analysis. Rats were sacrificed
      24 hours after intoxication, and tissues were collected for histopathologic
      evaluation. Data analysis included ANOVA procedures and contingency tables.
      RESULTS: Six of 8 cantharidin-intoxicated rats treated with mineral oil died;
      bradycardia and hypothermia developed in the animals of this group 0-8 hours
      after intoxication. Rats treated with mineral oil had higher urine cantharidin
      concentrations than rats receiving cantharidin alone or with smectite (P = .04).
      The most severe hypothermia (30.6 degrees C +/- 1.0) developed in rats
      administered mineral oil at 4-8 hours after intoxication, whereas those treated
      with charcoal (35.2 degrees C +/- 0.8) had mean body temperatures higher than all
      other treatment groups (P = .03). Survival times in the charcoal (P = .16) and
      smectite (P = .12) treatment groups were not statistically different from
      negative controls. CONCLUSIONS AND CLINICAL IMPORTANCE: Mineral oil is often used
      in the treatment of equine cantharidin toxicosis. Our findings suggest that
      mineral oil increases cantharidin absorption, worsening morbidity and fatality in
      rats.

PMID- 24033423
TI  - Accurate antemortem diagnosis of equine protozoal myeloencephalitis (EPM) based
      on detecting intrathecal antibodies against Sarcocystis neurona using the SnSAG2
      and SnSAG4/3 ELISAs.
AB  - BACKGROUND: Recent work demonstrated the value of antigen-specific antibody
      indices (AI and C-value) to detect intrathecal antibody production against
      Sarcocystis neurona for antemortem diagnosis of equine protozoal
      myeloencephalitis (EPM). OBJECTIVES: The study was conducted to assess whether
      the antigen-specific antibody indices can be reduced to a simple serum :
      cerebrospinal fluid (CSF) titer ratio to achieve accurate EPM diagnosis. ANIMALS:
      Paired serum and CSF samples from 128 horses diagnosed by postmortem examination.
      The sample set included 44 EPM cases, 35 cervical-vertebral malformation (CVM)
      cases, 39 neurologic cases other than EPM or CVM, and 10 non-neurologic cases.
      METHODS: Antibodies against S. neurona were measured in serum and CSF pairs using
      the SnSAG2 and SnSAG4/3 (SnSAG2, 4/3) ELISAs, and the ratio of each respective
      serum titer to CSF titer was determined. Likelihood ratios and diagnostic
      sensitivity and specificity were calculated based on serum titers, CSF titers,
      and serum : CSF titer ratios. RESULTS: Excellent diagnostic sensitivity and
      specificity was obtained from the SnSAG2, 4/3 serum : CSF titer ratio.
      Sensitivity and specificity of 93.2 and 81.1%, respectively, were achieved using
      a ratio cutoff of <=100, whereas sensitivity and specificity were 86.4 and 95.9%,
      respectively, if a more rigorous cutoff of <=50 was used. Antibody titers in CSF
      also provided good diagnostic accuracy. Serum antibody titers alone yielded much
      lower sensitivity and specificity. CONCLUSIONS AND CLINICAL IMPORTANCE: The study
      confirms the value of detecting intrathecal antibody production for antemortem
      diagnosis of EPM, and they further show that the antigen-specific antibody
      indices can be reduced in practice to a simple serum : CSF titer ratio.

PMID- 24033425
TI  - ACVIM member engagement and brand assessment survey: Corona Insights survey
      results summary.

PMID- 24033424
TI  - Expression of leptin and iNOS in oral melanomas in dogs.
AB  - BACKGROUND: Oral melanoma (OM) in dogs is an aggressive malignancy, with clinical
      behavior resembling cutaneous melanomas in humans. Melanoma in humans is promoted
      by an inflammatory environment that is contributed to by leptin and inducible
      nitric oxide synthase (iNOS). OBJECTIVE: To determine if the patterns of leptin
      and iNOS expression are similar in OM in dogs and cutaneous melanomas in humans.
      ANIMALS: Twenty client-owned dogs. METHODS: Retrospective case study.
      Immunostaining of the OM tumors from each dog was scored for percentage and
      intensity of leptin and iNOS expression. Mitotic index was used as an indicator
      of tumor aggression. RESULTS: Leptin was detected in >=75% of the tumor cells in
      specimens from 11 dogs. One tumor expressed leptin in <=25% of the cells. The
      intensity of leptin expression was variable with 6, 9, and 5 cases exhibiting low
      , moderate-, and high-intensity staining, respectively. OM with the lowest
      percentage of iNOS positive cells displayed the highest mitotic indices (P =
      .006, ANOVA). CONCLUSIONS AND CLINICAL IMPORTANCE: The expression of leptin is a
      common finding in melanomas in dogs. These data suggest that the possibility of
      future clinical applications, such as measuring the concentrations of plasma
      leptin as a screening tool or leptin as a target for therapy. The relevance of
      iNOS is not as clear in dogs with OM, for which other directed therapeutics might
      be more appropriate.

PMID- 24033427
TI  - Human embryonic stem cell differentiation into odontoblastic lineage: an in vitro
      study.
AB  - AIM: The aim of this study was to differentiate human embryonic stem cells
      (hESCs) into odontoblastic lineage in an optimized culture milieu. METHODOLOGY:
      In Phase 1, hESCs were differentiated into mesenchymal stem cells (H9-MSCs). In
      Phase 2, H9-MSCs were then differentiated into odontoblast-like cells (H9-Odont)
      under the stimulation of FGF-8 and BMP-4. Alternatively, H9-MSCs were
      differentiated into osteogenic lineage (H9-Osteo). In Phase 3, H9-Odont were
      seeded on 17% EDTA-treated dentine substrates in the presence of FGF-8 and BMP-4
      for further differentiation. All experiments were performed in triplicate (n =
      3). One-way anova was used to test hESC differentiation into different cell
      types. Post hoc Tukey's test was used to compare between groups. P < 0.05 was
      considered statistically significant. RESULTS: H9-Odont expressed the
      odontoblastic marker DSPP gene 125.47 +/- 0.1 (SD)-folds higher compared with H9
      MSCs at mRNA level (real-time RT-PCR). Additionally, the flow cytometry results
      revealed 53.1 +/- 3.4 (SD) % of DSP (+) cells in H9-Odont. Alternatively, H9
      Osteo expressed 5.9 +/- 2.2 (SD) % of DSP (+) cells. Moreover, the SEM results
      demonstrated that H9-Odont were found to undergo morphological changes from a
      fibroblast-like shape into more rounded shapes with cytoplasmic extensions into
      the dentinal tubules when seeded on 17% EDTA-treated dentine substrate in the
      presence of FGF-8 and BMP-4. However, H9-Osteo and H9-MSCs did not show similar
      morphological changes under similar culture milieu. CONCLUSION: This study
      supports the potential of hESCs as a stable, consistent, unlimited and 'off-the
      shelf' cell source to obtain odontoblastic cells for future clinical and research
      applications.

PMID- 24033426
TI  - Using autopsy brain tissue to study alcohol-related brain damage in the genomic
      age.
AB  - The New South Wales Tissue Resource Centre at the University of Sydney,
      Australia, is one of the few human brain banks dedicated to the study of the
      effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the
      National Network of Brain Banks and also focuses on schizophrenia and healthy
      control tissue. Alcohol abuse is a major problem worldwide, manifesting in such
      conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol
      dependency, and alcoholic neurodegeneration. The latter is also referred to as
      alcohol-related brain damage (ARBD). The study of postmortem brain tissue is
      ideally suited to determining the effects of long-term alcohol abuse, but it also
      makes an important contribution to understanding pathogenesis across the spectrum
      of alcohol misuse disorders and potentially other neurodegenerative diseases.
      Tissue from the bank has contributed to 330 peer-reviewed journal articles
      including 120 related to alcohol research. Using the results of these articles,
      this review chronicles advances in alcohol-related brain research since 2003, the
      so-called genomic age. In particular, it concentrates on transcriptomic
      approaches to the pathogenesis of ARBD and builds on earlier reviews of
      structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry
      2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539). 

PMID- 24033428
TI  - Anticancer effects of suberoylanilide hydroxamic acid in esophageal squamous
      cancer cells in vitro and in vivo.
AB  - The effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase
      inhibitor, have not been studied in esophageal squamous cell cancer (ESCC). Cell
      viability assay; flow cytometry for cell cycle and annexin V apoptosis assays;
      assays for cell migration, invasion, and adhesion to extracellular matrix (ECM);
      and immunoblotting and immunofluorescence staining were performed in three ESCC
      cell lines. Tumor xenograft with semiquantitative immunohistochemistry was used
      to study the effects of SAHA in vivo. SAHA effectively inhibited growth of ESCC
      cells with half-inhibitory concentrations (IC50 ) ranging from 2.6 to 6.5
      MUmol/L. SAHA restored acetylation of histone 3 lysine 9 (H3K9Ac) and histone 4
      lysine 12 (H4K12Ac) with an induction of G1 or G2 cell cycle arrest and
      apoptosis. Expression of cell cycle checkpoint regulatory proteins including
      cyclin-dependent kinases (CDKs) and cyclins was decreased, whereas expression of
      cell cycle suppressors, p21, p27, and Rb was increased in ESCC cells after SAHA
      treatment. SAHA inhibited migration, invasion, and ECM adhesion in ESCC cells
      with an induction of E-cadherin expression. SAHA significantly inhibited growth
      of ESCC tumors with increased expression of p21, p27, Rb, and E-cadherin while
      decreasing expression of CDK4 and cyclin D1 within the murine tumors. In
      conclusion, SAHA had antigrowth activity against ESCC cells in vitro and in vivo
      while inhibiting cell migration, cell invasion, and ECM adhesion, suggesting its
      potential as an epigenetic therapeutic agent for ESCC. 

PMID- 24033430
TI  - Accelerating type-specific ovarian carcinoma research: Calculator for Ovarian
      Subtype Prediction (COSP) is a reliable high-throughput tool for case review.
AB  - AIMS: The recent recognition that ovarian carcinoma is composed of five distinct
      disease entities has served to increase the value of accurate histotyping.
      Reliable identification of histotypes is essential for the success of studies
      testing novel therapies, as well as for biomarker discovery research. The aim of
      this study was to examine the utility of a nine-marker immunohistochemical (IHC)
      panel, designated the Calculator for Ovarian Subtype Prediction (COSP), to
      reliably reproduce the consensus diagnosis of two expert gynaecological
      pathologists. METHODS AND RESULTS: A total of 423 cases from the AGO-OVAR11 trial
      were evaluated using the COSP IHC panel, and compared to original diagnoses from
      >100 local contributing pathologists and independent expert gynaecopathology
      review. The overall concordance between COSP and expert review was 89%; in cases
      where a local pathologist's diagnosis was confirmed by COSP, the expert
      gynaecopathologist also agreed in 97.5% of cases. CONCLUSIONS: The incorporation
      of COSP into a high-throughput diagnostic review algorithm will decrease the need
      for expert review by identifying a small number of difficult cases that truly
      require expert review. This modification will serve to increase the efficiency of
      the diagnostic review process, which will probably serve to reduce operational
      costs and expedite translational studies on ovarian carcinoma.

PMID- 24033431
TI  - Eliminating visiting hour restrictions in hospitals.
AB  - BACKGROUND: Hospitals typically restrict visiting hours to ensure a restful
      environment for patients and to allow clinical staff to work. With increased
      public reporting focused on patient satisfaction and renewed efforts to improve
      patient and family engagement, hospitals may want to consider evaluating their
      current restrictions on visitation. Liberal visitation practices can decrease
      patient anxiety and benefit patients and families. METHODS: Morristown Medical
      Center, a 690-bed tertiary acute care facility and a 78-bed rehabilitation
      hospital, initiated a 24-h visitation policy. With input from nurses, physicians,
      administrators, and security, we developed a policy that emphasizes patient and
      staff safety and places the patient at the center of decision making. Comparison
      of patient satisfaction scores before and after the open visitation policy was
      implemented, which was made using the chi-square test. RESULTS: In the first 8
      months of the open visitation policy, the medical center received 14,444 "after
      hours" (8:00 p.m. to 5:00 a.m.) visitors. During this period, there was no
      increase in the number of complaints from patients or visitors. Incidence of
      security events did not change, despite the higher number of visitors. Patient
      satisfaction scores rose on both a commercial satisfaction survey and on the
      Hospital Consumer Assessment of Healthcare Providers and Systems survey. Unit
      staff received fewer phone calls for patient updates and acknowledged that the
      experience had been positive. DISCUSSION: Our experience suggests that
      implementation of open visitation at acute care and long-term care institutions
      can be accomplished with little disruption, is well utilized by visitors,
      improves the patient and family experience, and is generally accepted by hospital
      staff.

PMID- 24033429
TI  - Competition between isoprene emission and pigment synthesis during leaf
      development in aspen.
AB  - In growing leaves, lack of isoprene synthase (IspS) is considered responsible for
      delayed isoprene emission, but competition for dimethylallyl diphosphate (DMADP),
      the substrate for both isoprene synthesis and prenyltransferase reactions in
      photosynthetic pigment and phytohormone synthesis, can also play a role. We used
      a kinetic approach based on post-illumination isoprene decay and modelling DMADP
      consumption to estimate in vivo kinetic characteristics of IspS and
      prenyltransferase reactions, and to determine the share of DMADP use by different
      processes through leaf development in Populus tremula. Pigment synthesis rate was
      also estimated from pigment accumulation data and distribution of DMADP use from
      isoprene emission changes due to alendronate, a selective inhibitor of
      prenyltransferases. Development of photosynthetic activity and pigment synthesis
      occurred with the greatest rate in 1- to 5-day-old leaves when isoprene emission
      was absent. Isoprene emission commenced on days 5 and 6 and increased
      simultaneously with slowing down of pigment synthesis. In vivo Michaelis-Menten
      constant (Km ) values obtained were 265 nmol m(-2) (20 MUm) for DMADP-consuming
      prenyltransferase reactions and 2560 nmol m(-2) (190 MUm) for IspS. Thus, despite
      decelerating pigment synthesis reactions in maturing leaves, isoprene emission in
      young leaves was limited by both IspS activity and competition for DMADP by
      prenyltransferase reactions. 

PMID- 24033432
TI  - Multiple marker effects of single nucleotide polymorphisms in three genes,
      AKIRIN2, EDG1 and RPL27A, for marbling development in Japanese Black cattle.
AB  - Marbling in beef, measured by Beef Marbling Standard (BMS) number, is an
      economically important trait for beef cattle breeding and markets in Japan. We
      previously detected three single nucleotide polymorphisms (SNPs) associated with
      BMS number of Japanese Black in Oita prefecture: c.*188G>A in AKIRIN2,
      g.1471620G>T in EDG1 and g.3109537C>T in RPL27A. Here, we carried out single and
      multiple marker association analyses for the three SNPs in a different commercial
      Japanese Black population of 892 genotyped animals. The single marker analyses
      with the model including a single SNP showed significant associations of all SNPs
      with BMS number. The multiple marker analysis with the model including the main
      effects of the three SNPs and their interactions detected only significant main
      effects of g.1471620G>T and g.3109537C>T and a significant interaction between
      c.*188G>A and g.1471620G>T. These findings suggest the presence of inter-allelic
      interactions among genes affecting the development of beef marbling. For
      effective marker-assisted selection for BMS number, interactions among these
      markers need to be considered. 

PMID- 24033433
TI  - Complications related to invasive hemodynamic monitors during adult liver
      transplantation.
AB  - The rate of complications directly related to invasive monitors during liver
      transplantation (LT) was reviewed in 1206 consecutive adult LTs performed over
      8.6 yr (1/1/2004-7/31/2012). The designated anesthesiologists placed intra
      operative monitors, including two arterial catheters (via the radial and the
      right femoral arteries), central venous catheters (a 9 Fr. catheter and an 18 Fr.
      veno-venous bypass [VVB] return cannula in an internal jugular vein), a pulmonary
      artery catheter, and a transesophageal echocardiography (TEE) probe. A 17 Fr. VVB
      drainage cannula was placed via the left femoral vein. No Clavien-Dindo Grade V
      (death) or Grade IV (organ dysfunction) complication was identified. Nine Grade
      III complications (requiring surgical intervention) and 15 Grade II complications
      (conservative treatment) were noted. Seven (0.58% in 1206 cases) were related to
      a femoral arterial line with Grade III of four; seven (0.58%) were due to VVB
      return cannula in the femoral vein with Grade III of one; four (0.33%) were
      related to central venous catheters with Grade III of two; four (0.33%) were due
      to a TEE probe with Grade III of two; and two minor complications (0.17%) that
      were related to a radial arterial line. No complication was observed with a
      pulmonary arterial catheter. Current invasive monitors placed during LT have an
      acceptable risk.

PMID- 24033434
TI  - The Escherichia coli phylogenetic group B2 with integrons prevails in childhood
      recurrent urinary tract infections.
AB  - The aim of our study was to characterize the phylogenetic groups of Escherichia
      coli, antibiotic resistance, and containment of class 1 integrons in the first
      attack of pyelonephritis and in subsequent recurrences in young children.
      Altogether, 89 urine E. coli isolates from 41 children with urinary tract
      infection (UTI) were studied for prevalence and persistence of phylogenetic
      groups by pulsed-field gel electrophoresis (PFGE), antibacterial resistance by
      minimal inhibitory concentrations (MIC) and class 1 integrons by PCR.
      Phylogenetic group B2 was most common (57%), followed by D (20%), A (18%) and B1
      (5%). Overall resistance to betalactams was 61%, trimethoprim-sulfamethoxazole
      28%, and was not associated with phylogenetic groups. According to PFGE, the same
      clonal strain persisted in 77% of patients. The persistence was detected most
      often in phylogenetic group B2 (70%). Phylogenetic group B2 more often contained
      class 1 integrons than group A. Integron positive strains had higher MIC values
      of cefuroxime, cefotaxime, and gentamicin. In conclusion, phylogenetic group B2
      was the most common cause of the first episode of pyelonephritis, as well as in
      case of the persistence of the same strain and contained frequently class 1
      integrons in childhood recurrent UTI. An overall frequent betalactam resistance
      was equally distributed among phylogenetic groups.

PMID- 24033436
TI  - Patterns of selection and allele diversity of class I and class II major
      histocompatibility loci across the species range of sockeye salmon (Oncorhynchus
      nerka).
AB  - The major histocompatibility complex (MHC), an important component of the
      vertebrate immune system, provides an important suite of genes to examine the
      role of genetic diversity at non-neutral loci for population persistence. We
      contrasted patterns of diversity at the two classical MHC loci in sockeye salmon
      (Oncorhynchus nerka), MHC class I (UBA) and MHC class II (DAB), and neutral
      microsatellite loci across 70 populations spanning the species range from
      Washington State to Japan. There was no correlation in allelic richness or
      heterozygosity between MHC loci or between MHC loci and microsatellites. The two
      unlinked MHC loci may be responding to different selective pressures; the
      distribution of FST values for the two loci was uncorrelated, and evidence for
      both balancing and directional selection on alleles and lineages of DAB and UBA
      was observed in populations throughout the species range but rarely on both loci
      within a population. These results suggest that fluctuating selection has
      resulted in the divergence of MHC loci in contemporary populations. 

PMID- 24033437
TI  - Prevalence and quality of clinical pathways in Swedish intensive care units: a
      national survey.
AB  - RATIONALE, AIMS AND OBJECTIVES: To identify the prevalence of clinical pathways
      (CPs) in Swedish intensive care units (ICUs) and to explore the quality, content
      and evidence base of the documents. METHODS: A descriptive and explorative survey
      of all Swedish ICUs (N84) and a review of submitted examples of CPs (n12) were
      conducted. RESULTS: CPs were in use at 20% of the Swedish ICUs. There was a
      significant geographic variation but no relationship between the use of CPs and
      category of hospital, type of ICU, size of ICU or type of health record applied.
      In total, 56 CPs were reported within a range of scopes and extensions. The
      content of the ICUs' CPs, as well as the degree to which they were
      interprofessional, evidence based, and renewed varied. CONCLUSIONS: Progress has
      been made in relation to CPs in recent years, but there is potential for further
      improvements. None of the ICUs had CPs that contained all key characteristics of
      a high-quality, interprofessional and evidence-based CP identified in the
      literature. Greater knowledge sharing and cooperation within the field would be
      beneficial, and further research is needed.

PMID- 24033438
TI  - The posterior cingulate cortex as a plausible mechanistic target of meditation:
      findings from neuroimaging.
AB  - There has been an increased interest in mindfulness and meditation training over
      the past decade. As evidenced by exponential growth in the number of publications
      since the beginning of the 21st century, progressively more is becoming known
      about both the clinical efficacy and underlying neurobiological mechanisms of
      mindfulness training. This paper briefly highlights psychological models of
      stress that converge between ancient and modern day (e.g., operant conditioning);
      identifies key brain regions that, with these models, are biologically plausible
      targets for mindfulness (e.g., posterior cingulate cortex); and discusses recent
      and emerging findings from neuroimaging studies of meditation therein, including
      new advances using real-time functional magnetic resonance imaging neurofeedback
      in neurophenomenological studies. 

PMID- 24033439
TI  - Phosphorylation of tau protein at sites Ser(396-404) is one of the earliest
      events in Alzheimer's disease and Down syndrome.
AB  - AIMS: Phosphorylation, conformational changes and cleavage of tau protein have
      been widely suggested to contribute to abnormal tau processing in the
      pathogenesis of Alzheimer's disease, as well as in other tauopathies.
      Consistently, many phosphorylated sites, such as Ser(199-202) -Thr(205) and
      Ser(396-404) , have been associated with this pathological processing. The
      present study examined the chronological appearance of phosphorylation during the
      neurofibrillary tangle (NFT) evolution in Alzheimer disease (AD) and Down
      syndrome. METHODS: Immunohistochemistry for modified tau [phosphorylated at
      Ser(199-202) -Thr(205) (AT8) and Ser(396-404) (PHF-1) or truncated at D(421)
      (TauC3) and E(391) (MN423)] was performed on paraffin-embedded human brain
      sections. Double immunofluorescence for phosphorylated and truncated tau was used
      to detect intensity and distribution of tau immunoreactivity, and provided
      detailed characterization of NFT pathology. RESULTS: Phosphorylation at sites
      Ser(396-404) was significantly increased when compared with phosphorylations at
      sites Ser(199-202) -Thr(205) . Around 50% of the total structures containing
      phosphorylation at sites Ser(396-404) were found as early phospho-tau aggregates
      with a well-preserved neuronal soma. Phosphorylation of tau protein at sites
      Ser(396) coexists with early and late truncation events. Tau abnormal processing
      in Down syndrome consistently showed similar alterations as observed in AD.
      CONCLUSION: Phosphorylation of tau protein at the carboxyl terminus may be among
      the earliest tau events, and it occurs prior to the apparition of the classical
      fibrillar structure. Finally, these data validate PHF-1 as an efficient marker
      for AD cytopathology following the progression of tau aggregation into NFT.

PMID- 24033441
TI  - Biodiversity offsets and the challenge of achieving no net loss.
AB  - Businesses, governments, and financial institutions are increasingly adopting a
      policy of no net loss of biodiversity for development activities. The goal of no
      net loss is intended to help relieve tension between conservation and development
      by enabling economic gains to be achieved without concomitant biodiversity
      losses. biodiversity offsets represent a necessary component of a much broader
      mitigation strategy for achieving no net loss following prior application of
      avoidance, minimization, and remediation measures. However, doubts have been
      raised about the appropriate use of biodiversity offsets. We examined what no net
      loss means as a desirable conservation outcome and reviewed the conditions that
      determine whether, and under what circumstances, biodiversity offsets can help
      achieve such a goal. We propose a conceptual framework to substitute the often ad
      hoc approaches evident in many biodiversity offset initiatives. The relevance of
      biodiversity offsets to no net loss rests on 2 fundamental premises. First,
      offsets are rarely adequate for achieving no net loss of biodiversity alone.
      Second, some development effects may be too difficult or risky, or even
      impossible, to offset. To help to deliver no net loss through biodiversity
      offsets, biodiversity gains must be comparable to losses, be in addition to
      conservation gains that may have occurred in absence of the offset, and be
      lasting and protected from risk of failure. Adherence to these conditions
      requires consideration of the wider landscape context of development and offset
      activities, timing of offset delivery, measurement of biodiversity, accounting
      procedures and rule sets used to calculate biodiversity losses and gains and
      guide offset design, and approaches to managing risk. Adoption of this framework
      will strengthen the potential for offsets to provide an ecologically defensible
      mechanism that can help reconcile conservation and development. Balances de
      Biodiversidad y el Reto de No Obtener Perdida Neta. 

PMID- 24033440
TI  - Laser and light-based treatment of Keloids--a review.
AB  - BACKGROUND: Keloids are an overgrowth of fibrotic tissue outside the original
      boundaries of an injury and occur secondary to defective wound healing. Keloids
      often have a functional, aesthetic, or psychosocial impact on patients as
      highlighted by quality-of-life studies. OBJECTIVES: Our goal is to provide
      clinicians and scientists an overview of the data available on laser and light
      based therapies for treatment of keloids, and highlight emerging light-based
      therapeutic technologies and the evidence available to support their use.
      METHODS: We employed the following search strategy to identify the clinical
      evidence reported in the biomedical literature: in November 2012, we searched
      PubMed.gov, Ovid MEDLINE, Embase and Cochrane Reviews (1980-present) for
      published randomized clinical trials, clinical studies, case series and case
      reports related to the treatment of keloids. The search terms we utilized were
      'keloid(s)' AND 'laser' OR 'light-emitting diode' (LED) OR 'photodynamic therapy'
      (PDT) OR 'intense pulsed light' OR 'low level light' OR 'phototherapy.' RESULTS:
      Our search yielded 347 unique articles. Of these, 33 articles met our inclusion
      and exclusion criteria. CONCLUSION: We qualitatively conclude that laser and
      light-based treatment modalities may achieve favourable patient outcomes.
      Clinical studies using CO2 laser are more prevalent in current literature and a
      combination regimen may be an adequate ablative approach. Adding light-based
      treatments, such as LED phototherapy or PDT, to laser treatment regimens may
      enhance patient outcomes. Lasers and other light-based technology have introduced
      new ways to manage keloids that may result in improved aesthetic and symptomatic
      outcomes and decreased keloid recurrence.

PMID- 24033442
TI  - Stem cells: a recapitulation of development.
AB  - Pluripotent stem cells are cells that can differentiate into any tissue from all
      germ layers and include embryonic stem cells and induced pluripotent cells (iPS).
      Embryonic stem cells are derived from 8-day blastocysts obtained from unutilized
      embryos following in vitro fertilization, while iPS is obtained following
      transfection of dermal fibroblasts with pluripotent genes (sex determining region
      Y-binding, Kruppel-like factor 4, octamer-binding transcription factor 4 and c
      Myc). The major challenge is to differentiate these cells into lung epithelium
      for therapeutic applications as well as to model lung diseases such as cystic
      fibrosis. In this review, the developmental pathways of the lung and how these
      pathways have been recapitulated in vitro to induce differentiation of
      pluripotent cells to lung epithelium were examined. 

PMID- 24033443
TI  - Could plant lectins become promising anti-tumour drugs for causing autophagic
      cell death?
AB  - Plant lectins, a group of highly diverse carbohydrate-binding proteins of non
      immune origin, are ubiquitously distributed through a variety of plant species,
      and have recently drawn rising attention due to their remarkable ability to kill
      tumour cells using mechanisms implicated in autophagy. In this review, we provide
      a brief outline of structures of some representative plant lectins such as
      concanavalin A, Polygonatum cyrtonema lectin and mistletoe lectins. These can
      target autophagy by modulating BNIP-3, ROS-p38-p53, Ras-Raf and PI3KCI-Akt
      pathways, as well as Beclin-1, in many types of cancer cells. In addition, we
      further discuss how plant lectins are able to kill cancer cells by modulating
      autophagic death, for therapeutic purposes. Together, these findings provide a
      comprehensive perspective concerning plant lectins as promising new anti-tumour
      drugs, with respect to autophagic cell death in future cancer therapeutics. 

PMID- 24033444
TI  - Comparison of innate immune activation after prolonged feeding of milk fermented
      with three species of Lactobacilli.
AB  - The present investigation aimed at identifying the abilities of three different
      species of probiotic lactobacilli to modulate cellular immune responses in mouse
      neutrophils and macrophages in vivo over a study period of 60 days. Neutrophil
      respiratory burst enzymes (cytochrome c reductase and MPO) showed remarkable
      increased activity (P <= 0.01) after consumption of milks fermented by different
      species of probiotics over 30 and 60 days of feeding trials. Enzyme activities
      (beta-galactosidase and beta-glucuronidase) and nitric oxide production also
      increased considerably (P <= 0.01) in macrophages, both in peritoneal fluid and
      in enriched cell cultures. The effects of enhanced enzyme activities were
      corroborated by simultaneous increases in the phagocytic activities of
      neutrophils and macrophages. The increases in cellular functions were invariably
      maximal during the first 30 days of study and were maintained, but did not
      increase, over the next 30 days. Further, Lactobacillus helveticus-fed groups
      were most effective at modulating neutrophil functions whereas Lactobacillus
      paracasei-fed groups were more potent at enhancing macrophage functions.
      Together, our results indicate that probiotics have strain specific effects on
      stimulating cellular functions while not causing excessive stimulation of the
      immune system over longer feeding periods, thereby resulting in maximum and
      stable health benefits. 

PMID- 24033445
TI  - Neoadjuvant chemotherapy with gemcitabine plus carboplatin followed by immediate
      radical cystectomy for muscle-invasive bladder cancer.

PMID- 24033446
TI  - Preoperative level of serum amyloid A is superior to C-reactive protein in the
      prognosis of esophageal squamous cell carcinoma.
AB  - Preoperative elevations in the levels of serum amyloid A (SAA) or C-reactive
      protein (CRP) have been reported to be prognostic indicators in several
      malignancies. The aim of this study is to evaluate the serum levels of SAA and
      CRP in the prognosis of esophageal squamous cell carcinoma (ESCC). In total, 252
      patients with ESCC who had undergone surgery with curative-intent were
      retrospectively recruited. The specificity, sensitivity, and prognostic value of
      SAA or CRP levels were measured as the area under the receiver operating
      characteristic (ROC) curve (AUC). The clinical value of SAA and CRP levels as
      prognostic indicators was evaluated using Cox's proportional hazards model. The 1
      , 3-, and 5-year overall survival (OS) rates for the entire cohort of patients
      with ESCC were 71.0%, 61.0%, and 43.0%, respectively. The correlation between the
      levels of SAA and CRP was significant (r(2) = 0. 685, P < 0.001). The ROC
      analysis showed that the levels of CRP were associated with a significantly lower
      overall accuracy than were the SAA levels (AUC, 0.615 vs. 0.880; P < 0.001). For
      the complete cohort, the median OS was 52.0 months longer in patients with low
      preoperative serum levels of SAA (72.0 months) compared with patients who had
      high SAA levels (20.0 months, P < 0.001). The median OS among patients with low
      CRP levels was also longer compared with the patients who had high CRP levels
      (72.0 vs. 51.0 months, respectively; P < 0.001). Subgroup analyses showed that
      the preoperative elevated levels of SAA could find significant differences in OS
      for stage I, stage II, and stage III (P < 0.001, P = 0.001, and P < 0.001,
      respectively), whereas the increased levels of CRP could only find a difference
      in OS for stage II cancers. After a multivariate analysis, preoperative elevated
      level of SAA was found to be an independently and significant prognostic factor
      (P < 0.001). Our study indicates that the preoperative levels of SAA and CRP can
      act as prognostic factors, and that elevated levels of these proteins are
      associated with negative effects on the survival of patients with ESCC. SAA
      showed a higher prognostic value than CRP in both cohort and subgroup analysis. 

PMID- 24033447
TI  - The impact of loupes and microscopes on vision in endodontics.
AB  - AIM: To report on an intraradicular visual test in a simulated clinical setting
      under different optical conditions. METHODOLOGY: Miniaturized visual tests with E
      optotypes (bar distance from 0.01 to 0.05 mm) were fixed inside the root canal
      system of an extracted maxillary molar at different locations: at the orifice, a
      depth of 5 mm and the apex. The tooth was mounted in a phantom head for a
      simulated clinical setting. Unaided vision was compared with Galilean loupes
      (2.5* magnification) with integrated light source and an operating microscope (6*
      magnification). The influence of the dentists' age within two groups was
      evaluated: <40 years (n = 9) and >=40 years (n = 15). RESULTS: Some younger
      dentists were able to identify the E-optotypes at the orifice, but otherwise,
      natural vision did not reveal any measurable result. With Galilean loupes, the
      younger dentists <40 years could see a 0.05 mm structure at the root canal
      orifice, in contrast to the older group >=40 years. Only the microscope allowed
      the observation of structures inside the root canal, independent of age.
      CONCLUSION: Unaided vision and Galilean loupes with an integrated light source
      could not provide any measurable vision inside the root canal, but younger
      dentists <40 years could detect with Galilean loupes a canal orifice
      corresponding to the tip of the smallest endodontic instruments. Dentists over 40
      years of age were dependent on the microscope to inspect the root canal system.

PMID- 24033448
TI  - Successful failure: good for the self and science.

PMID- 24033450
TI  - Regarding "feasibility and safety of same-day discharge after implantable
      cardioverter defibrillator placement for primary prevention".

PMID- 24033451
TI  - Light induces jasmonate-isoleucine conjugation via OsJAR1-dependent and 
      independent pathways in rice.
AB  - The bioactive form of jasmonate is the conjugate of the amino acid isoleucine
      (Ile) with jasmonic acid (JA), which is biosynthesized in a reaction catalysed by
      the GH3 enzyme JASMONATE RESISTANT 1 (JAR1). We examined the biochemical
      properties of OsJAR1 and its involvement in photomorphogenesis of rice (Oryza
      sativa). OsJAR1 has a similar substrate specificities as its orthologue in
      Arabidopsis. However, osjar1 loss-of-function mutants did not show as severe
      coleoptile phenotypes as the JA-deficient mutants coleoptile photomorphogenesis 2
      (cpm2) and hebiba, which develop long coleoptiles in all light qualities we
      examined. Analysis of hormonal contents in the young seedling stage revealed that
      osjar1 mutants are still able to synthesize JA-Ile conjugate in response to blue
      light, suggesting that a redundantly active enzyme can conjugate JA and Ile in
      rice seedlings. A good candidate for this enzyme is OsJAR2, which was found to be
      able to catalyse the conjugation of JA with Ile as well as with some additional
      amino acids. In contrast, if plants in the vegetative stage were mechanically
      wounded, the content of JA-Ile was severely reduced in osjar1, demonstrating that
      OsJAR1 is the most important JA-Ile conjugating enzyme in the wounding response
      during the vegetative stage.

PMID- 24033452
TI  - Phenotypic and genetic trends of patellar luxation in Dutch Flat-Coated
      Retrievers.
AB  - Canine patellar luxation has been described in various dog breeds, with high
      prevalence especially in smaller dogs. Most dogs suffer from medial displacement
      of the patella, although in larger dogs lateral displacement is also seen. A sex
      predisposition has been described for females. Patellar luxation is considered a
      polygenic, multifactorial disorder. From 1990 to 2007, in total 3834 Flat-Coated
      Retrievers were screened; 23.6% of those animals were affected with patellar
      luxation. Lateral displacement of the patella was most common in this breed (61%
      of cases), whereas medial (31% of cases) and lateral and medial (8% of cases)
      were less common. Unilateral involvement (51% of cases) was just as often
      observed as was bilateral involvement (49% of cases). Females were more often
      affected with patellar luxation (30% of all tested females) than were males (17%
      of all tested males). The heritability of patellar luxation was 0.17 +/- 0.03 in
      this population, and breeding with one affected parent increased the prevalence
      of patellar luxation in offspring by 45% compared to that with two unaffected
      parents. Since the start of the screening program, there was an initial decrease
      from 28% to 18% in incidence, but this stagnated thereafter. The annual average
      estimated breeding values followed the same pattern. With approximately one
      quarter of the Dutch Flat-Coated Retrievers being affected with patellar
      luxation, this population shows unusually high prevalence compared with reports
      in other large-breed dogs. The heritability for patellar luxation in this
      population was moderate (0.17), indicating that environmental factors play a
      large role in the manifestation of the disorder. A screening program reduced the
      prevalence of patellar luxation in this breed, but improvement has recently
      stagnated. Inclusion of breeding values in the screening program could improve
      its effectiveness. 

PMID- 24033453
TI  - Using "near misses" analysis to prevent wrong-site surgery.
AB  - The purpose of our pre-post intervention study was to reduce the number of near
      miss events pertaining to wrong-site surgery, including incorrectly sided
      surgical bookings and incorrectly performed preoperative time-out procedures. Pre
      and postintervention, incorrectly booked cases, and improperly performed
      presurgical time-out procedures were recorded. We then educated each surgeon and
      their staff regarding the importance of and proper way to perform these tasks.
      Subsequently, the monthly percentage of incorrectly booked surgical procedures
      and improperly performed time-outs were significantly decreased. INTRODUCTION: In
      2004, the Joint Commission published comprehensive guidelines to prevent wrong
      site surgery. Seven years have passed, and the incidence has not declined. The
      Joint Commission estimates that in the United States, wrong-site procedures
      including surgeries occur at least 40 times a week. "Near misses" are events that
      could have harmed a patient, but did not due to chance or mitigation. Improperly
      performed time-out procedures and inaccurate surgical bookings are considered
      near misses and could ultimately lead to "never events," such as wrong-site
      surgery. Near-miss analysis is a highly effective method of preventing rare,
      "never events." We hypothesize that proper education of surgeons and staff will
      be effective in reducing the number of near misses. METHODS: All cases analyzed
      were performed at an academic, orthopedic surgery specialty institution. From
      August 2010 to May 2011, near misses were identified and stored in Patient Safety
      Net (PSN), an electronic database. We tracked these cases and educated each
      offending attending physician and his or her staff about the importance of
      accurate surgical bookings. Additionally, we began an observational program to
      carefully review presurgical time-out procedures as they occurred. We tracked the
      percentage of these improperly performed time-outs and counseled offenders
      (attending surgeon, or any member of the operating room staff who made the error)
      regarding the deficiencies that caused the time-out to be ineffective. The number
      of near misses that occurred before and after the interventions were recorded and
      analyzed. RESULTS: Of the 12,215 cases included in this study, 6,126 cases
      formulated the "pre-education" cohort, while a total of 6,089 cases formulated
      the "post-education" cohort. In the first four months of the study, the monthly
      rate of incorrectly booked cases was 0.75%. Since the intervention, the rate
      decreased to 0.41% (p = .0139). The percentage of improperly performed time-out
      procedures decreased from 18.7% to 5.9% after the educational interventions were
      performed (p < .0001). CONCLUSION: A program designed to educate physicians to
      the importance of decreasing near misses for wrong-site surgery is effective.
      When analyzing the literature, it is clear that the reduction in near misses
      observed in this study decreases the likelihood of a wrong-site surgery.

PMID- 24033455
TI  - Wound events in kidney transplant patients receiving de novo everolimus: a pooled
      analysis of three randomized controlled trials.
AB  - Data were pooled from three prospective, multicenter trials in which 1996 de novo
      kidney transplant recipients were randomized to everolimus 1.5 or 3.0 mg or
      mycophenolic acid (MPA), with cyclosporine and steroids. Wound healing
      complications reported as adverse events were retrospectively reviewed in a
      blinded manner. The incidence of wound healing adverse events was 17.6% (351 of
      1996) by day 90 and was similar for everolimus 1.5 mg (16.6% [110 of 661]) vs.
      MPA (14.3% [95 of 665]) (p = 0.255), but higher with everolimus 3.0 mg (21.8%
      [146 of 670]) (p < 0.001 vs. MPA). Similar results were observed for wound
      healing complications reported as serious adverse events. The 12-month incidence
      of lymphocele was 11.2% with everolimus 1.5 mg and 8.9% with MPA (p = 0.171), but
      lymphocele reported as a serious adverse event were more frequent with everolimus
      1.5 mg (6.5% vs. 3.5%; p = 0.012). The hazard ratio (HR) for any wound healing
      complication vs. MPA was not significantly higher for everolimus <3 ng/mL (HR
      1.33; 95% CI 0.94-1.88; p = 0.104), but increased to 1.46 (95% CI 1.12-1.90; p =
      0.005) for 3-8 ng/mL and 1.69 (95% CI 1.20-2.38; p = 0.002) for >8 ng/mL. These
      results suggest that de novo kidney transplant patients receiving an initial
      everolimus dose of 1.5 mg do not appear to have a pronounced increased risk of
      wound healing complications vs. patients receiving MPA.

PMID- 24033454
TI  - Effects of ethanol on immune response in the brain: region-specific changes in
      adolescent versus adult mice.
AB  - BACKGROUND: Alcohol use occurs across the life span beginning in adolescence and
      continuing through adulthood. Ethanol (EtOH)-induced pathology varies with age
      and includes changes in neurogenesis, neurodegeneration, and glial cell
      activation. EtOH-induced changes in glial activation and immune activity are
      believed to contribute to EtOH-induced neuropathology. Recent studies indicate an
      emerging role of glial-derived neuroimmune molecules in alcohol abuse and
      addiction. METHODS: Adolescent and adult C57BL/6 mice were treated via gavage
      with 6 g/kg EtOH for 10 days, and tissue was harvested 1 day post treatment. We
      compared the effects of EtOH on chemokine and cytokine expression and astrocyte
      glial fibrillary acidic protein (GFAP) immunostaining and morphology in the
      hippocampus, cerebellum, and cerebral cortex. RESULTS: EtOH increased mRNA levels
      of the chemokine CCL2/MCP-1 in all 3 regions of adult mice relative to controls.
      The cytokine interleukin-6 (IL-6) was selectively increased only in the adult
      cerebellum. EtOH did not affect mRNA levels of the cytokine tumor necrosis factor
      alpha (TNF-alpha) in any of these brain regions in adult animals. Interestingly,
      CCL2, IL-6, and TNF-alpha mRNA levels were not increased in the hippocampus,
      cerebellum, or cortex of adolescent mice. EtOH treatment of adult and adolescent
      mice resulted in increased GFAP immunostaining. CONCLUSIONS: Collectively, these
      data indicate an age- and region-specific susceptibility to EtOH regulation of
      neuroinflammatory and addiction-related molecules as well as astrocyte phenotype.
      These studies may have important implications concerning differential alcohol
      induced neuropathology and alcohol addiction across the life span.

PMID- 24033457
TI  - Adaptive response in stress granule formation and bulk translational repression
      upon a combined stress of mild heat shock and mild ethanol stress in yeast.
AB  - The formation of cytoplasmic mRNA-protein complex granules termed 'processing
      bodies and stress granules' is often induced in the stress responses of
      eukaryotic cells. Most previous studies on stress granules have focused on the
      response to a single type of stress, and little information is available about
      the response to combined stress. Additionally, the effects of adaptation on
      stress granule formation and bulk translation activity are poorly understood. We
      investigated the formation of stress granules upon combined exposure to mild heat
      shock (37  degrees C) and mild ethanol stress (5% v/v) in Saccharomyces
      cerevisiae. Although neither stress alone induced stress granule formation, their
      combination caused a pronounced repression of translation activity and the
      formation of stress granules. Pretreatment with each mild stress significantly
      attenuated the formation of stress granules and caused changes in the composition
      of stress granules upon the subsequent combined stress and facilitated stress
      granule disassembly accompanied by smooth translational resurrection during the
      recovery process, indicating that yeast cells can induce adaptations in stress
      granule formation. However, the pretreated cells still exhibited a severe
      repression of translation activity. These findings provide novel and fundamental
      insight into the regulation of yeast stress granules. 

PMID- 24033456
TI  - Evidence for the role of vacuolar soluble pyrophosphatase and inorganic
      polyphosphate in Trypanosoma cruzi persistence.
AB  - Trypanosoma cruzi infection leads to development of a chronic disease but the
      mechanisms that the parasite utilizes to establish a persistent infection despite
      activation of a potent immune response by the host are currently unknown. Unusual
      characteristics of T. cruzi are that it possesses cellular levels of
      pyrophosphate (PPi ) at least 10 times higher than those of ATP and molar levels
      of inorganic polyphosphate (polyP) within acidocalcisomes. We characterized an
      inorganic soluble EF-hand containing pyrophosphatase from T. cruzi (TcVSP) that,
      depending on the pH and cofactors, can hydrolyse either pyrophosphate (PPi ) or
      polyphosphate (polyP). The enzyme is localized to both acidocalcisomes and
      cytosol. Overexpression of TcVSP (TcVSP-OE) resulted in a significant decrease in
      cytosolic PPi , and short and long-chain polyP levels. Additionally, the TcVSP-OE
      parasites showed a significant growth defect in fibroblasts, less responsiveness
      to hyperosmotic stress, and reduced persistence in tissues of mice, suggesting
      that PPi and polyP are essential for the parasite to resist the stressful
      conditions in the host and to maintain a persistent infection. 

PMID- 24033458
TI  - Southern montane populations did not contribute to the recolonization of West
      Siberian Plain by Siberian larch (Larix sibirica): a range-wide analysis of
      cytoplasmic markers.
AB  - While many species were confined to southern latitudes during the last
      glaciations, there has lately been mounting evidence that some of the most cold
      tolerant species were actually able to survive close to the ice sheets. The
      contribution of these higher latitude outposts to the main recolonization thrust
      remains, however, untested. In the present study, we use the first range-wide
      survey of genetic diversity at cytoplasmic markers in Siberian larch (Larix
      sibirica; four mitochondrial (mt) DNA loci and five chloroplast (cp) DNA SSR
      loci) to (i) assess the relative contributions of southern and central areas to
      the current L. sibirica distribution range; and (ii) date the last major
      population expansion in both L. sibirica and adjacent Larix species. The
      geographic distribution of cpDNA variation was uninformative, but that of
      mitotypes clearly indicates that the southernmost populations, located in
      Mongolia and the Tien-Shan and Sayan Mountain ranges, had a very limited
      contribution to the current populations of the central and northern parts of the
      range. It also suggests that the contribution of the high latitude cryptic
      refugia was geographically limited and that most of the current West Siberian
      Plain larch populations likely originated in the foothills of the Sayan
      Mountains. Interestingly, the main population expansion detected through
      Approximate Bayesian Computation (ABC) in all four larch species investigated
      here pre-dates the LGM, with a mode in a range of 220,000-1,340,000 years BP.
      Hence, L. sibirica, like other major conifer species of the boreal forest, was
      strongly affected by climatic events pre-dating the Last Glacial Maximum.

PMID- 24033459
TI  - Fructose, pregnancy and later life impacts.
AB  - Fructose is an increasingly common constituent of the Westernized diet due to
      cost and production efficiencies. Although an integral component of our pre
      industrial revolution diet, over the past two decades human and animal studies
      have highlighted that excessive fructose intake appears to be associated with
      adverse metabolic effects. Excessive intake of fructose is the combined result of
      increased total energy consumption and increased portion sizes of foods, which
      often incorporate the fructose-containing sugars sucrose and high-fructose corn
      syrup (HFCS). The adverse metabolic effects following excessive fructose
      consumption have become a hot topic in mainstream media and there is now rigorous
      scientific debate regarding periods of exposure, dosage levels, interactive
      effects with other sugars and fats and mechanisms underlying the actions of
      fructose. There is still a degree of controversy regarding the extent to which
      sugars such as sucrose and HFCS have contributed to the current epidemic of
      obesity and diabetes. Furthermore, an increasing number of infants are being
      exposed to sugar-sweetened food and beverages before birth and during early
      postnatal life, highlighting the importance of determining the long-term effects
      of this perinatal exposure on the developing offspring. There are limited human
      observational and controlled studies identifying associations of excessive
      sweetened food and beverage consumption with poor pregnancy outcomes. Animal
      research has demonstrated an increased incidence of gestational diabetes as well
      as altered maternal, fetal and offspring metabolic function, although the long
      term effects and the mechanism underlying these perturbations are ill defined.
      This review aims to understand the role of early life fructose exposure in
      modifying postnatal risk of disease in the offspring, focusing on fructose intake
      during pregnancy and in early postnatal life. 

PMID- 24033460
TI  - Roles of patch characteristics, drought frequency, and restoration in long-term
      trends of a widespread amphibian.
AB  - Despite the high profile of amphibian declines and the increasing threat of
      drought and fragmentation to aquatic ecosystems, few studies have examined long
      term rates of change for a single species across a large geographic area. We
      analyzed growth in annual egg-mass counts of the Columbia spotted frog (Rana
      luteiventris) across the northwestern United States, an area encompassing 3
      genetic clades. On the basis of data collected by multiple partners from 98 water
      bodies between 1991 and 2011, we used state-space and linear-regression models to
      measure effects of patch characteristics, frequency of summer drought, and
      wetland restoration on population growth. Abundance increased in the 2 clades
      with greatest decline history, but declined where populations are considered most
      secure. Population growth was negatively associated with temporary hydroperiods
      and landscape modification (measured by the human footprint index), but was
      similar in modified and natural water bodies. The effect of drought was mediated
      by the size of the water body: populations in large water bodies maintained
      positive growth despite drought, whereas drought magnified declines in small
      water bodies. Rapid growth in restored wetlands in areas of historical population
      declines provided strong evidence of successful management. Our results highlight
      the importance of maintaining large areas of habitat and underscore the greater
      vulnerability of small areas of habitat to environmental stochasticity. Similar
      long-term growth rates in modified and natural water bodies and rapid, positive
      responses to restoration suggest pond construction and other forms of management
      can effectively increase population growth. These tools are likely to become
      increasingly important to mitigate effects of increased drought expected from
      global climate change. Papeles de las Caracteristicas del Fragmento, Frecuencia
      de Sequia y Restauracion en las Tendencias a Largo Plazo de un Anfibio
      Ampliamente Distribuido. 

PMID- 24033461
TI  - Addiction research centres and the nurturing of creativity: the Kurihama medical
      and addiction centre-a profile.
AB  - The Kurihama Medical and Addiction Center began to conduct research and to
      provide medical care for alcohol-related problems in 1963, when special
      alcoholism treatment wards were established in Japan for the first time. At
      first, the provision of medical care to patients was prioritized. However,
      training courses for specialists were initiated in 1975, and the Department of
      Clinical Research was established in 1984, which led to the formation of the
      present management structure in which the centre's staff are shared by three
      departments: Medical Care, Clinical Research and Education and Information. The
      Department of Medical Care provides specialized treatment for alcohol use
      disorders and medical services for other conditions, including behavioural
      addictions such as internet addiction and gambling disorder, as well as dementia
      and other psychiatric disorders. The Departments of Clinical Research and
      Education and Information are engaged mainly in specialized activities related to
      alcohol. The Department of Clinical Research conducts research on the
      epidemiology of alcohol use, the effects of alcohol on health and the treatment
      of alcohol use disorders in Japan, in cooperation with universities and other
      research institutions. The Department of Education and Information fosters the
      human capacity to achieve the primary, secondary and tertiary prevention of
      alcohol-related problems and the dissemination of information on alcohol. The
      centre also performs alcohol-related problem prevention activities, government
      consultations and international collaborative research and personal exchanges,
      thereby functioning as a central institution for alcohol policy-based medical
      services and research in Japan. 

PMID- 24033462
TI  - Emphysema and pulmonary fibrosis: coincidence or conspiracy?

PMID- 24033463
TI  - Chemical properties of upland forest soils in the Catskills region.
AB  - The Catskills forest provides a valuable array of ecosystem services for local
      and regional populations, including the provision of forest products, wildlife
      habitats, and high-quality water. These services depend on chemical and
      biological processes that occur in forest soils. In 2011, we sampled soils in 25
      headwater catchments in the Catskills region to quantify the pools of soil
      nutrients and examine the variation in soil properties in the region. The average
      soil depth in the 50 excavated pits was 56.6 cm. Average soil mass was 205
      kg/m(2). The pools of soil carbon and nitrogen averaged 58.5 and 3.95 Mg/ha,
      respectively. The thin organic horizons accounted for less than 1% of soil mass,
      but included 14% of the soil carbon and 11% of soil nitrogen. Catskills forest
      soils are highly acidic, with mean pH ranging between 3.9 and 4.75. Base
      saturation was high (>60%) in organic horizons and low (12-31%) in mineral soils.
      The pool of exchangeable calcium is approximately equivalent to 20 years of
      calcium export from headwater streams, raising concerns regarding the ability of
      these catchments to maintain current stream calcium concentrations. The data and
      samples collected in this study provide a baseline for future soil monitoring in
      the region.

PMID- 24033464
TI  - Efficacy and complications of urinary drainage procedures in idiopathic
      retroperitoneal fibrosis complicated by extrinsic ureteral obstruction.
AB  - OBJECTIVE: To investigate the efficacy and complications of urinary drainage
      procedures in patients with idiopathic retroperitoneal fibrosis complicated by
      ureteral obstruction. METHODS: A retrospective study of 30 idiopathic
      retroperitoneal fibrosis patients involving 44 obstructed urinary units who
      underwent urinary drainage from January 2002 through April 2010 was carried out.
      Data of all diagnostic procedures, blood and urine cultures, and hospital
      admissions were collected and analyzed. RESULTS: In 12 of 44 (27%) cases,
      percutaneous nephrostomy was carried out at the first step. Attempted ureteral
      stenting at the first step was successful in 25 of 32 (79%) cases, of which 20
      (80%) cases could be managed successfully by ureteral stenting alone throughout
      the study period. Successful prolonged urinary drainage with percutaneous
      nephrostomy alone was accomplished in 10 cases, three at the first step and seven
      at the second step after failed intraureteral stent insertion or after
      unsuccessful maintenance of urinary drainage with an intraureteral stent. A total
      of 21 urinary tract infection episodes occurred in 11 patients. The incidence and
      accumulated incidence of acute pyelonephritis was 0.062 episodes/100 person-days
      and 30%, respectively. The incidence and accumulated incidence of urosepsis was
      0.015 episodes/100 person-days and 6.6%, respectively. The overall number of
      complications did not differ between external and internal urinary drainage
      procedures (percutaneous nephrostomy, 21% vs intraureteral stent, 17.9%; P =
      0.79). CONCLUSION: Both intraureteral stent and percutaneous nephrostomy
      placement are a safe way to relieve urinary obstruction in idiopathic
      retroperitoneal fibrosis patients, and they have comparable complication rates.
      Over time, the need for using both management options in the same patient might
      be required. Hence, these techniques should be regarded as complementary.

PMID- 24033465
TI  - Audiological abnormalities in patients with alopecia areata.
AB  - BACKGROUND: Audiological abnormalities seen in various autoimmune disorders
      raises the question of whether such abnormalities also exist in alopecia areata.
      OBJECTIVE: This study was performed to detect possible audiological abnormalities
      in Alopecia areata (AA) patients. METHODS: The study population consisted of 51
      patients with AA and 51 healthy controls. Autoscopic and audiometric examinations
      of both ears were performed in patients and controls. Audiometric examinations
      were performed using a pure tone audiometer in a silent cabin. Pure tone
      thresholds were determined for each ear at frequencies of 250-16000 Hz for air
      conduction. RESULTS: Sensorineural hypoacusis was found in 28 patients with AA
      (54.9%). Six of these 28 patients showed unilateral minimal hearing loss (>30 dB)
      at high frequencies only (4000-16 000 Hz), while 22 showed bilateral minimal
      hearing loss (>30 dB) at high frequencies only (4000-16 000 Hz). Hypoacusis was
      observed in 13 control subjects (25.4%). Sensorineural hypoacusis was
      significantly more frequent in AA patients than controls (P = 0.002). CONCLUSION:
      Follicular melanocytes may be an important target in the autoimmune process of AA
      and AA may have an effect on hearing function by affecting the melanocytes in the
      inner ear. Therefore, there may be a relationship between sensorineural hearing
      loss and the autoimmune disease, AA.

PMID- 24033466
TI  - Is the reciprocating movement per se able to improve the cyclic fatigue
      resistance of instruments?
AB  - AIM: To compare cyclic fatigue resistance of two geometrically similar nickel
      titanium instruments, used in conditions similar to clinical use in reciprocating
      and continuous rotary motion. METHODOLOGY: Four groups of eighteen instruments
      each, Reciproc((r)) files sizes ISO 25 and 40 (R25 and R40) and Mtwo((r)) files
      sizes ISO 25 and 40 (M25 and M40), were tested in reciprocating and continuous
      rotary motion, employing a novel experiment device. An artificial root canal
      (diameter, 1.4 mm; angle of curvature, 60  degrees ; and curvature radius, 5 mm)
      was milled into a stainless steel block. To simulate clinical conditions, instead
      of rotating the file in static position, the set-up was designed to produce a
      continuous up-and-down pecking motion along the vertical axis of the instrument.
      Time to fracture (TTF) and push-pull cycles (PPC) were recorded, the number of
      cycles to fracture (NCF) was determined, and fractured instrument surfaces were
      examined under a scanning electron microscope (SEM). RESULTS: Mean time to
      fracture was 34.44 +/- 8.58 min for R25 in reciprocation motion, 35.77 +/- 4.82
      min for R40 in reciprocation motion, 12.15 +/- 1.74 min for M25 in continuous
      rotary motion and 13.27 +/- 2.02 min for M40 in continuous rotary motion, whereas
      28.52 +/- 3.27 min for R25 in continuous rotary motion, 23.87 +/- 1.52 min for
      R40 in continuous rotary motion, 31.07 +/- 1.79 min for M25 in reciprocation
      motion and 31.08 +/- 3.26 min for M40 in reciprocation motion. There was a
      significant difference (P < 0.0001) for the cyclic fatigue resistance between the
      reciprocation motion and the continuous rotary motion groups. Reciproc((r)) files
      in reciprocating movement had a significantly higher NCF than Mtwo((r)) files,
      when used in continuous rotation. The highest resistance to failure was shown by
      Reciproc((r)) files in reciprocation movement, followed by Mtwo((r)) files in
      reciprocation and Reciproc((r)) files in continuous motion. Mtwo((r)) files in
      continuous rotary movement had the least resistance. SEM analysis of the fracture
      surface confirmed typical features of cyclic fatigue failure. CONCLUSION:
      Reciprocating movement increased the cyclic fatigue resistance of NiTi
      instruments.

PMID- 24033467
TI  - In silico analysis and experimental validation of molecular mechanisms of
      salvianolic acid A-inhibited LPS-stimulated inflammation, in RAW264.7
      macrophages.
AB  - OBJECTIVES: The aim of this study was to explore mechanisms by which salvianolic
      acid A (SAA) revealed its anti-inflammatory activity, in lipopolysaccharide (LPS)
      stimulated RAW264.7 cells. MATERIALS AND METHODS: Nitric oxide (NO) concentration
      was determined by the Griess reaction and cell viability was assessed by MTT
      assay. Interleukin-6, TNFalpha and interleukin-1beta were determined by ELISA.
      The RAW264.7 cells were transfected with siRNA against p38 or HO-1. Expressions
      of COX-2, inducible NO synthase (iNOS), NF-kappaB, HO-1, p-p38 and
      phosphorylation of IkappaB kinase alpha/beta were detected by western blotting.
      Potential targets of SAA were analysed by homology modelling, target prediction,
      protein-protein interaction prediction and docking studies. RESULTS: Salvianolic
      acid A suppressed LPS-triggered production of NO, TNFalpha and Interleukin-6. It
      also reduced protein expression of inducible NO synthase and COX-2, and reduced
      translocation of NF-kappaB to nuclei. Moreover, SAA promoted expression of
      phosphorylated p38, and downstream HO-1. Zn (II) protoporphyrin IX, a specific
      inhibitor of HO-1, or siRNA against HO-1 could effectively increase transfer of
      NF-kappaB. SAA was predicted to target amyloid-beta protein-like protein and
      arachidonate 5-lipoxygenase, that could regulate p38 and HO-1. CONCLUSIONS: In
      silico analysis and experimental validation together demonstrated that SAA
      exhibited its anti-inflammatory effect via the p38-HO-1 pathway in LPS-stimulated
      RAW264.7 cells, reduced transfer of NF-kappaB to the nuclei and thus reduced
      production of inflammatory mediators.

PMID- 24033468
TI  - Relationship between gamma-interferon gene polymorphisms and susceptibility to
      brucellosis infection.
AB  - Interferon-gamma (IFN-gamma) is a pro-inflammatory cytokine that plays a pivotal
      role in the defense mechanism against Brucella infection. It was hypothesized
      that the IFN-gamma in (+874 A/T in intron 1) TT and +5644 T/A, TT genotypes,
      which are reportedly associated with high IFN production, are associated with
      susceptibility to brucellosis in Iranian subjects. Genotyping of these IFN-gamma
      variants by an allele-specific polymerase chain reaction method was performed in
      281 subjects, comprising 153 patients with active brucellosis and 128 healthy
      controls. It was found that the +874 minor allele (A) and homozygote genotype
      (AA) were significantly more frequently present in brucellosis patients than in
      controls (OR = 2.588; 95% CI, 1.313-5.104; P = 0.006 for the AA genotype; OR =
      1.575; 95% CI, 1.124-2.216; P = 0.010 for the A allele). However, the allelic and
      genotypic distribution of the IFN-gamma polymorphism at position UTR5644 A>T did
      not differ significantly between patients and controls (P > 0.05). The
      distribution of haplotypes in this study suggests that the T/A haplotype
      (+874/UTR5644), which was present more frequently in controls than in patients,
      may protect subjects against Brucella infection. It is suggested that IFN-gamma
      +874 AA genotype and A allele are risk factors for developing brucellosis
      infection in Iranian subjects. 

PMID- 24033469
TI  - Intra-VTA deltorphin, but not DPDPE, induces place preference in ethanol-drinking
      rats: distinct DOR-1 and DOR-2 mechanisms control ethanol consumption and reward.
AB  - BACKGROUND: While there is a growing body of evidence that the delta opioid
      receptor (DOR) modulates ethanol (EtOH) consumption, development of DOR-based
      medications is limited in part because there are 2 pharmacologically distinct DOR
      subtypes (DOR-1 and DOR-2) that can have opposing actions on behavior. METHODS:
      We studied the behavioral influence of the DOR-1-selective agonist [D-Pen(2) ,D
      Pen(5) ]-Enkephalin (DPDPE) and the DOR-2-selective agonist deltorphin
      microinjected into the ventral tegmental area (VTA) on EtOH consumption and
      conditioned place preference (CPP) and the physiological effects of these 2 DOR
      agonists on GABAergic synaptic transmission in VTA-containing brain slices from
      Lewis rats. RESULTS: Neither deltorphin nor DPDPE induced a significant place
      preference in EtOH-naive Lewis rats. However, deltorphin (but not DPDPE) induced
      a significant CPP in EtOH-drinking rats. In contrast to the previous finding that
      intra-VTA DOR-1 activity inhibits EtOH consumption and that this inhibition
      correlates with a DPDPE-induced inhibition of GABA release, here we found no
      effect of DOR-2 activity on EtOH consumption nor was there a correlation between
      level of drinking and deltorphin-induced change in GABAergic synaptic
      transmission. CONCLUSIONS: These data indicate that the therapeutic potential of
      DOR agonists for alcohol abuse is through a selective action at the DOR-1 form of
      the receptor.

PMID- 24033470
TI  - Remote monitoring of left ventricular assist device parameters after HeartAssist
      5 implantation.
AB  - Although several left ventricular assist devices (LVADs) have been used widely,
      remote monitoring of LVAD parameters has been available only recently. We present
      our remote monitoring experience with an axial-flow LVAD (HeartAssist-5, MicroMed
      Cardiovascular, Inc., Houston, TX, USA). Five consecutive patients who were
      implanted a HeartAssist-5 LVAD because of end-stage heart failure due to ischemic
      (n=4) or idiopathic (n=1) cardiomyopathy, and discharged from hospital between
      December 2011 and January 2013 were analyzed. The data (pump speed, pump flow,
      power consumption) obtained from clinical visits and remote monitoring were
      studied. During a median follow-up of 253 (range: 80-394) days, fine tuning of
      LVADs was performed at clinical visits. All patients are doing well and are in
      New York Heart Association Class-I/II. A total of 39 alarms were received from
      three patients. One patient was hospitalized for suspected thrombosis and was
      subjected to physical examinations as well as laboratory and echocardiographic
      evaluations; however, no evidence of thrombus washout or pump thrombus was found.
      The patient was treated conservatively. Remaining alarms were due to insufficient
      water intake and were resolved by increased water consumption at night and summer
      times, and fine tuning of pump speed. No alarms were received from the remaining
      two patients. We believe that remote monitoring is a useful technology for early
      detection and treatment of serious problems occurring out of hospital thereby
      improving patient care. Future developments may ease troubleshooting, provide
      more data from the patient and the pump, and eventually increase physician and
      patient satisfaction. Despite all potential clinical benefits, remote monitoring
      should be taken as a supplement to rather than a substitute for routine clinical
      visits for patient follow-up.

PMID- 24033472
TI  - Anatomical and histological organization of the testes of the inseminating
      catfish Trachelyopterus striatulus (Steindachner, 1877) (Siluriformes:
      Auchenipteridae).
AB  - The testicular morphology, spermatogenesis and occurrence of sperm in the ovarian
      lumen of Trachelyopterus striatulus were studied using anatomical, histological
      and biometric techniques. A total of 50 catfish (T. striatulus) were captured,
      measuring 14.9 +/- 2.5 cm of standard length, body weight was 81.2 +/- 34.5 g and
      their testes weighed 16.9 +/- 6.1 g. The testes of T. striatulus are paired
      organs, showing two distinct regions: cranial, which shows a compact medial part
      and with fringes ventrally, and caudal region, which is formed of the seminal
      vesicle with fringes laterally and two saculiform expansions. The testes
      presented a length of 35.2 +/- 6.9 mm, and the fringes showed a cranial length of
      12.1 +/- 3.8 mm and caudal length of 6.4 +/- 2.6 mm. Histologically, the cranial
      fringes are spermatogenic and showed cells with significantly different nuclear
      diameters, ranging from 8.2 +/- 1.5 MUm (primary spermatogonia) to 1.88 +/- 0.3
      MUm (spermatid). The seminal vesicles and saculiform expansions showed tubules
      with a simple prismatic secretory epithelium containing spermatozoa and secretion
      into the lumen. The caudal fringes are exclusively for secretory flow, consisting
      of tubules with a simple cuboidal epithelium. The common spermatic duct showed a
      simple cuboidal epithelium and contained spermatozoa with secretion into the
      lumen. The secretion of the caudal region is acidophilic, with neutral
      glycoproteins and sialomucin. T. striatulus ovaries showed free spermatozoa or
      were organized in spermatozeugmata into the ovarian lumen and between the
      ovuligers lamellae.

PMID- 24033473
TI  - Increased amoeboid microglial density in the olfactory bulb of Parkinson's and
      Alzheimer's patients.
AB  - The olfactory bulb (OB) is affected early in both Parkinson's (PD) and
      Alzheimer's disease (AD), evidenced by the presence of disease-specific protein
      aggregates and an early loss of olfaction. Whereas previous studies showed
      amoeboid microglia in the classically affected brain regions of PD and AD
      patients, little was known about such changes in the OB. Using a morphometric
      approach, a significant increase in amoeboid microglia density within the
      anterior olfactory nucleus (AON) of AD and PD patients was observed. These
      amoeboid microglia cells were in close apposition to beta-amyloid,
      hyperphosphorylated tau or alpha-synuclein deposits, but no uptake of
      pathological proteins by microglia could be visualized. Subsequent analysis
      showed (i) no correlation between microglia and alpha-synuclein (PD), (ii) a
      positive correlation with beta-amyloid (AD), and (iii) a negative correlation
      with hyperphosphorylated tau (AD). Furthermore, despite the observed pathological
      alterations in neurite morphology, neuronal loss was not apparent in the AON of
      both patient groups. Thus, we hypothesize that, in contrast to the classically
      affected brain regions of AD and PD patients, within the AON rather than neuronal
      loss, the increased density in amoeboid microglial cells, possibly in combination
      with neurite pathology, may contribute to functional deficits. 

PMID- 24033474
TI  - Associations of single nucleotide polymorphisms in candidate genes with the
      polled trait in Datong domestic yaks.
AB  - The domestic yak (Bos grunniens) is an iconic symbol of animal husbandry at high
      altitudes. Yaks exhibit unique external characteristics including long hair and
      large horns. However, hornless yaks can be found in different breeds and
      different populations. The hornless trait is also known as polled, and the POLL
      locus has been fine-mapped to chromosome 1 in cattle (Bos taurus), although the
      underlying genetic basis of the polled trait is still unclear in the yak. Thus,
      we performed an association study to identify the genetic polymorphisms
      responsible for the polled trait in the yak. Fifty polled Datong domestic yaks
      and 51 horned individuals were selected randomly from a huge herd and were used
      as the case and control groups respectively for the association analysis. Twelve
      genes located in the candidate region of the POLL locus in cattle were used as
      references to detect DNA polymorphisms related to yak polledness, which were
      analyzed by sequencing and a high-resolution melting test. We applied Fisher's
      exact test and haplotype analysis to show that a 147-kb segment that included
      three protein-coding genes C1H21orf62, GCFC1 and SYNJ1 was the most likely
      location of the POLL mutation in domestic yaks. 

PMID- 24033476
TI  - Expansion of acute flaccid paralysis surveillance: beyond poliomyelitis.

PMID- 24033475
TI  - Multicenter review of liver transplant for hepatitis B-related liver disease:
      disparities in gender and ethnicity.
AB  - Orthotopic liver transplantation (OLT) is the preferred treatment for selected
      patients with hepatitis B virus (HBV)-related liver disease. This study aimed to
      (i) define long-term outcomes following OLT for HBV; (ii) to quantify the
      incidence of HBV recurrence (rHBV) as it relates to anti-HBV treatment; and (iii)
      to determine outcomes for specific patient subgroups. We performed a
      retrospective chart review of 738 patients undergoing OLT between 1985 and 2010
      at seven US transplant centers and divided the patients into 3 eras, 1985-1994,
      1995-2004, and 2005-2010, based on hepatitis B immunoglobulin and antiviral
      therapies. In Era 3, female gender (p = 0.002), recurrent hepatocellular cancer
      (p < 0.001), and retransplantation (p = 0.01) were significantly associated with
      worse survival on multivariate analysis. Survival at three yr was poor for all
      ethnicities in Era 1, but significantly improved for all except black Americans
      by Era 3. Era 2 data showed a continued increase in rHBV from five to 10 yr
      (16.6%, 26.2%). In conclusion, while OLT outcomes have improved because of
      combination antiviral and immunoglobulin therapy, women and black Americans may
      not have realized an equal benefit. The rate of rHBV is significant even 10 yr
      post-transplant with survival affected.

PMID- 24033477
TI  - Feasibility of esophagogastric junction distensibility measurement during Nissen
      fundoplication.
AB  - Increased esophagogastric junction distensibility has been implicated in the
      development of gastroesophageal reflux disease (GERD). Previous authors have
      demonstrated a reduction in distensibility following anti-reflux surgery, but the
      changes during the operation are not clear. Our study aimed to ascertain the
      feasibility of measuring intraoperative distensibility changes and to assess if
      this would have potential to modify the operation. Seventeen patients with GERD
      were managed in a standardized manner consisting of preoperative assessment with
      symptom scoring, endoscopy, 24 hours pH studies, and manometry. Patients then
      underwent laparoscopic Nissen fundoplication with intraoperative distensibility
      measurement using an EndoFLIP EF-325 functional luminal imaging probe (Crospon
      Ltd, Galway, Ireland). This device utilizes impedance planimetry technology to
      measure cross-sectional area and distensibility within a balloon-tipped catheter.
      This is inflated at the esophagogastric junction to fixed distension volumes.
      Thirty-second median cross-sectional area and intraballoon pressure measurements
      were recorded at 30 and 40 mL balloon distensions. Measurement time points were
      initially after induction of anesthesia, after pneumoperitoneum, after hiatal
      mobilization, after hiatal repair, after fundoplication, and finally pre
      extubation. Postoperatively, patients continued on protocol and were discharged
      after a two-night stay tolerating a sloppy diet. Patients with a hiatus hernia on
      high-resolution manometry had a significantly higher initial esophagogastric
      junction distensibility index (DI) than those without. Hiatus repair and
      fundoplication resulted in a significant overall reduction in the median DI from
      the initial to final recordings (30 mL balloon distension reduction of 3.26 mm(2)
      /mmHg (P = 0.0087), 40 mL balloon distension reduction of 2.39 mm(2) /mmHg [P =
      0.0039]). There was also a significant reduction in the DI after
      pneumoperitoneum, hiatus repair, and fundoplication at 40 mL balloon distension.
      Two individual cases in the series highlight the utility of the system in
      potentially changing the operation. After fundoplication, patient 7 recorded a DI
      of 0.47 mm(2) /mmHg, the lowest in our series, and subsequently required
      reoperation because of significant symptoms of dysphagia. Patient 12 had a
      fundoplication that appeared visually too tight and was converted
      intraoperatively to a Lind 270 degrees  wrap resulting in a change in the DI from
      0.65 to 0.89 mm(2) /mmHg. Laparoscopic Nissen fundoplication results in a
      significant reduction in the distensibility of the esophagogastric junction. The
      EndoFLIP system is able to demonstrate significant changes during the operation
      and may help guide intraoperative modification. Larger multicenter studies with
      long-term follow up would be beneficial to develop a target range of
      distensibility associated with good outcome. 

PMID- 24033478
TI  - Insulin dysregulation.
AB  - Abnormalities of insulin metabolism include hyperinsulinaemia and insulin
      resistance, and these problems are collectively referred to as insulin
      dysregulation in this review. Insulin dysregulation is a key component of equine
      metabolic syndrome: a collection of endocrine and metabolic abnormalities
      associated with the development of laminitis in horses, ponies and donkeys.
      Insulin dysregulation can also accompany prematurity and systemic illness in
      foals. Causes of insulin resistance are discussed, including pathological
      conditions of obesity, systemic inflammation and pituitary pars intermedia
      dysfunction, as well as the physiological responses to stress and pregnancy. Most
      of the discussion of insulin dysregulation to date has focused on insulin
      resistance, but there is increasing interest in hyperinsulinaemia itself and
      insulin responses to feeding. An oral sugar test or in-feed oral glucose
      tolerance test can be performed to assess insulin responses to dietary
      carbohydrates, and these tests are now recommended for use in clinical practice.
      Incretin hormones are likely to play an important role in postprandial
      hyperinsulinaemia and are the subject of current research. Insulin resistance
      exacerbates hyperinsulinaemia, and insulin sensitivity can be measured by
      performing a combined glucose-insulin test or i.v. insulin tolerance test. In
      both of these tests, exogenous insulin is administered and the rate of glucose
      uptake into tissues measured. Diagnosis and management of hyperinsulinaemia is
      recommended to reduce the risk of laminitis. The term insulin dysregulation is
      introduced here to refer collectively to excessive insulin responses to sugars,
      fasting hyperinsulinaemia and insulin resistance, which are all components of
      equine metabolic syndrome. 

PMID- 24033479
TI  - Secretion of atypical protein substrates by the ESAT-6 secretion system of
      Staphylococcus aureus.
AB  - Staphylococcus aureus encodes the specialized ESAT-6 Secretion System (ESS). EsxA
      and EsxB are secreted by the ESS pathway, and share sequence features of ESAT-6
      and CFP-10 of the Type VII Secretion System (T7SS) of Mycobacterium tuberculosis.
      Unlike ESAT-6 and CFP-10, EsxA and EsxB do not interact. Instead, EsxB associates
      with a novel substrate, EsxD, and EsxA dimerizes with itself or EsxC (EsaC).
      Unlike EsxA and EsxB, EsxC and EsxD do not share obvious sequence features of
      WXG100 proteins nor PE/PPE and Esp families of proteins, all of which belong to
      the pfam EsxAB clan of mycobacterial T7SS. EsxD carries the C-terminal motif
      YxxxD/E that has been proposed to target T7 substrates for secretion in
      mycobacteria. Here, we find that deletion, but not amino acid substitutions, in
      this motif prevent secretion of EsxA and EsxC but not EsxB or EsxD. This is
      unlike the genetic inactivation of esxA, esxB, esxC or esxD that leads to loss of
      secretion of all four substrates. Thus, substrate secretion can be uncoupled by
      deleting the last six amino acids of EsxD. The physical association of EsxC and
      EsxD with canonical WXG100 proteins suggests that these proteins belong to the
      EsxAB clan. 

PMID- 24033480
TI  - Differential trafficking of saccharidic probes following aspirin in clinical
      tests of intestinal permeability in young healthy women.
AB  - The effects of inflammatory changes on the absorption of different-sized probes
      and their permeability ratios are poorly understood. The aim of the present study
      was to determine the effects of a pharmacological agent on the permeability of
      the gut mucosa to saccharidic probes of larger and smaller molecular weight.
      Permeability was assessed by half-hourly urinary excretion of a combined dose of
      d-mannitol, l-rhamnose and lactulose following consumption of a single 600 mg
      dose of aspirin and compared with a placebo in a cross-over study in 20 healthy
      female volunteers. The temporal patterns of excretion of all probes were bimodal,
      being best fitted by polynomial functions. The relatively small early peak was
      evident for at least 4 h for smaller sugars, but was less evident with lactulose,
      being overshadowed by a larger second peak. These conclusions were further
      supported by separate analyses of the segments of the temporal plots between 2.5
      and 4 h and between 4.5 and 6 h. The forms of these curves did not change
      significantly following dosing with aspirin. A greater proportion of the total
      dose of mannitol than rhamnose was excreted over the collection period. Following
      the consumption of aspirin, the cumulative rate of excretion of the smaller
      sugars (i.e. mannitol and rhamnose) was significantly reduced whereas that of
      lactulose was increased over the 6 h collection period. Aspirin has opposite
      effects on the absorption of larger and smaller probes, influencing the outcome
      of the test. These results have important consequences for the design and
      comparison of clinical tests of permeability.

PMID- 24033481
TI  - Pleiotropy in the melanocortin system: expression levels of this system are
      associated with melanogenesis and pigmentation in the tawny owl (Strix aluco).
AB  - The adaptive function of melanin-based coloration is a long-standing debate. A
      recent genetic model suggested that pleiotropy could account for covariations
      between pigmentation, behaviour, morphology, physiology and life history traits.
      We explored whether the expression levels of genes belonging to the melanocortin
      system (MC1R, POMC, PC1/3, PC2 and the antagonist ASIP), which have many
      pleiotropic effects, are associated with melanogenesis (through variation in the
      expression of the genes MITF, SLC7A11, TYR, TYRP1) and in turn melanin-based
      coloration. We considered the tawny owl (Strix aluco) because individuals vary
      continuously from light to dark reddish, and thus, colour variation is likely to
      stem from differences in the levels of gene expression. We measured gene
      expression in feather bases collected in nestlings at the time of melanin
      production. As expected, the melanocortin system was associated with the
      expression of melanogenic genes and pigmentation. Offspring of darker reddish
      fathers expressed PC1/3 to lower levels but tended to express PC2 to higher
      levels. The convertase enzyme PC1/3 cleaves the POMC prohormone to obtain ACTH,
      while the convertase enzyme PC2 cleaves ACTH to produce alpha-melanin-stimulating
      hormone (alpha-MSH). ACTH regulates glucocorticoids, hormones that modulate
      stress responses, while alpha-MSH induces eumelanogenesis. We therefore conclude
      that the melanocortin system, through the convertase enzymes PC1/3 and PC2, may
      account for part of the interindividual variation in melanin-based coloration in
      nestling tawny owls. Pleiotropy may thus account for the covariation between
      phenotypic traits involved in social interactions (here pigmentation) and life
      history, morphology, behaviour and physiology. 

PMID- 24033482
TI  - Are physician productivity and quality of care related?
AB  - This study examines the relationship between clinical quality of care and
      physician productivity in the public sector clinical setting. This longitudinal
      study takes place in Jefferson County, Alabama using data from six public sector
      clinics. Data representing 21 physicians across 13 consecutive quarters
      representing 44,765 person observations were analyzed. Four variables were
      selected to represent quality of care for this pediatric patient population; two
      of which pertained to antibiotic use and two pertained to asthma care. Findings
      from multivariate analyses examining each quality of care measure and controlling
      for other visit and practice characteristics indicate that three of the four
      quality measures were significantly related to productivity. Specifically, the
      percent of asthma patients with documented asthma severity classification was
      negatively related to physician productivity (beta = -.24, p = .04), although the
      magnitude of this relationship was small. The percent of asthma patients
      prescribed an inhaled corticosteroid who also had a severity classification was
      negatively related to physician productivity (beta = -.23, p = .03) and the
      percent of patients prescribed oral antibiotics was marginally negatively related
      to physician productivity (beta = -.09, p = .09). In general, findings suggest
      that a relationship exists between quality of healthcare and physician
      productivity. Future research should continue to examine this relationship across
      other disciplines and healthcare settings. 

PMID- 24033483
TI  - Immunodiagnosis of sheep infections with Echinococcus granulosus: in 35 years
      where have we come?
AB  - W. K. Yong and D. D. Heath published in 1979 a seminal paper in the first issue
      of Parasite immunology describing their efforts to determine whether the arc 5
      precipitin band, formed when test human serum is reacted against electrophoresed
      hydatid cyst fluid antigen, would be a suitable immunodiagnostic test for the
      identification of sheep infected with Echinococcus granulosus. Although they
      found antibodies to arc 5 in the sera of hydatid-infected sheep, the sera of some
      sheep harbouring Taenia ovis and T. hydatigena also precipitated the hydatid cyst
      fluid arc 5 antigen, so they concluded arc 5 antibodies were not suitable for the
      specific immunodiagnosis of E. granulosus infection in sheep in New Zealand.
      Subsequent work has shown that the existence of multiple infections with
      different taeniid species, antigenic cross-reactivity between these related
      parasites and the low level of specific antibody response to infection continue
      to hinder efforts to improve the diagnosis of hydatid infection in sheep and
      other natural intermediate hosts, thereby preventing the development of any
      practical test. In particular, the poor antibody response of ruminants to
      naturally acquired hydatid infection may prove an insurmountable barrier in
      future efforts to develop a reliable and accurate immunological test.

PMID- 24033484
TI  - Clonal seborrheic keratosis: dermoscopic and confocal microscopy
      characterization.
AB  - BACKGROUND: The diagnosis of clonal seborrheic keratosis may be challenging
      clinically and histologically. OBJECTIVE: In our study, we describe the common
      aspects of this benign entity that show peculiar dermoscopic and confocal
      findings. METHODS: A total of nine clonal seborrheic keratosis were analyzed.
      RESULTS: Upon dermoscopy, it reveals the presence of globular-like structures and
      sharply demarcated borders whereas confocal microscopy displays the typical
      intraepidermal nesting of pigmented keratinocytes that permits to have a reliable
      in vivo diagnosis. CONCLUSIONS: Dermoscopy and confocal microscopy permit to in
      vivo diagnose this variant of seborrheic keratosis.

PMID- 24033485
TI  - Hydrogeochemistry of the Catskill Mountains of New York.
AB  - Major ion chemistry of Catskill region groundwater is characterized on the basis
      of 207 analyses compiled from three sources, including a web-based U.S.
      Geological Survey database, state agency regulatory compliance data, and sampling
      of trailside springs performed by the authors. All samples were analyzed for the
      complete set of major ions, including calcium, magnesium, sodium, potassium,
      bicarbonate, chloride, sulfate, and nitrate. Groundwater in pristine, high
      elevation areas of the Catskill Peaks was found to be predominantly of calcium
      bicarbonate, calcium sulfate, or calcium bicarbonate-sulfate types, with
      relatively low ionic strength. Groundwater at lower elevations along the margins
      of the region or in valley bottoms was predominantly of sodium-chloride or sodium
      bicarbonate types, showing the effects of road salt and other local pollution
      sources. Nitrate and sulfate enrichment attributable to regional air pollution
      sources were most evident in the high-elevation spring samples, owing to the
      generally low concentrations of other major ions. Trailside springs appear to be
      viable low-cost sources for obtaining samples representative of groundwater,
      especially in remote and inaccessible areas of the Catskill forest preserve. 

PMID- 24033486
TI  - Polysomnographic evaluation of non-invasive ventilation in children with
      neuromuscular disease.
AB  - BACKGROUND AND OBJECTIVE: In the last 20 years, research efforts have been
      focused on the use of non-invasive ventilation (NIV) as a mean of avoiding
      tracheostomy in patients affected by neuromuscular diseases (NMD). Nocturnal NIV
      has been a particular focus as sleep is a risk factor for respiratory failure in
      NMD patients. The objective of our study was to evaluate the efficacy of
      nocturnal NIV in improving the respiratory function of NMD patients evaluated by
      polysomnography (PSG) and arterial blood gas (ABG) analysis parameters. METHODS:
      Ten children affected by NMD underwent PSG and ABG analysis evaluation at the
      onset of their respiratory failure and during nocturnal NIV therapy. RESULTS: We
      found a statistically significant improvement of the lowest oxygen desaturation
      (nadir SaO2 ), apnoea-hypopnoea index (AHI) and oxygen desaturation index (ODI)
      after NIV treatment in all patients. Mean SaO2 also improved, although this
      result was not statistical significant, while the percentage of episodes of
      desaturation with a SaO2 <90% and <80% decreased with a statistical significance
      (P < 0.0001). After NIV, only one patient showed an episode of desaturation
      lasting more than 5 min (10.6 min length), and we also found an improvement of
      daytime blood gas parameters with a normalization of these indexes. CONCLUSIONS:
      NIV was effective in improving respiratory parameters at night in patients
      affected by respiratory muscular weakness, as evaluated by PSG and ABG analysis.

PMID- 24033487
TI  - Association of dilated cardiomyopathy with the striatin mutation genotype in
      boxer dogs.
AB  - BACKGROUND: Myocardial disease in the Boxer dog is characterized by 1 of 2
      clinical presentations, dilated cardiomyopathy (DCM) characterized by ventricular
      systolic dysfunction, dilatation and tachyarrhythmias, and arrhythmogenic right
      ventricular cardiomyopathy (ARVC) characterized by ventricular tachyarrhythmias,
      syncope, and sudden death. Boxer ARVC has been associated with a deletion in the
      striatin gene in some families. HYPOTHESIS/OBJECTIVES: We hypothesized that both
      presentations represent a single disease, and the development of DCM in the Boxer
      is associated with the striatin deletion. ANIMALS: Thirty-three adult Boxer dogs
      with DCM, 29 adult Boxer dogs with the striatin deletion and ARVC, and 16 Boxers
      without cardiac disease. METHODS: DNA samples were evaluated for the striatin
      deletion. Association of the deletion with the DCM phenotype was tested by a
      Fisher's exact test. T-tests were used to evaluate potential differences between
      the positive heterozygous and positive homozygous groups with DCM with regard to
      age, LVIDD, LVIDS, and FS%. RESULTS: Thirty of 33 dogs with DCM were positive for
      the striatin deletion. The striatin mutation and the homozygous genotype were
      strongly associated with the DCM phenotype (P < .001 and P = .005). There was no
      statistical difference between the heterozygous and homozygous groups with regard
      to age and echocardiographic measurements. CONCLUSIONS AND CLINICAL IMPORTANCE:
      This study demonstrates an association between DCM in the Boxer dog and the
      striatin mutation, particularly with the homozygous genotype. The observation
      that 3/33 dogs developed DCM and lacked the striatin mutation suggests that there
      is at least 1 other cause of DCM in the Boxer dog.

PMID- 24033488
TI  - Impact of neighborhood biomass cooking patterns on episodic high indoor
      particulate matter concentrations in clean fuel homes in Dhaka, Bangladesh.
AB  - Exposure to particulate matter (PM2.5 ) from the burning of biomass is associated
      with increased risk of respiratory disease. In Dhaka, Bangladesh, households that
      do not burn biomass often still experience high concentrations of PM2.5 , but the
      sources remain unexplained. We characterized the diurnal variation in the
      concentrations of PM2.5 in 257 households and compared the risk of experiencing
      high PM2.5 concentrations in biomass and non-biomass users. Indoor PM2.5
      concentrations were estimated every minute over 24 h once a month from April 2009
      through April 2010. We found that households that used gas or electricity
      experienced PM2.5 concentrations exceeding 1000 MUg/m(3) for a mean of 35 min
      within a 24-h period compared with 66 min in biomass-burning households. In both
      households that used biomass and those that had no obvious source of particulate
      matter, the probability of PM2.5 exceeding 1000 MUg/m(3) were highest during
      distinct morning, afternoon, and evening periods. In such densely populated
      settings, indoor pollution in clean fuel households may be determined by biomass
      used by neighbors, with the highest risk of exposure occurring during cooking
      periods. Community interventions to reduce biomass use may reduce exposure to
      high concentrations of PM2.5 in both biomass and non-biomass using households. 

PMID- 24033489
TI  - Laparoscopic limited liver resection decreases morbidity irrespective of the
      hepatic segment resected.
AB  - OBJECTIVES: The laparoscopic approach is widely used in abdominal surgery.
      However, the benefits of laparoscopy in liver surgery have hitherto been
      insufficiently established. This study sought to investigate these benefits and,
      in particular, to establish whether or not the laparoscopic approach is
      beneficial in patients with lesions involving the posterosuperior segments of the
      liver. METHODS: Outcomes in a cohort of patients undergoing mostly minor
      hepatectomy (50 laparoscopic and 52 open surgery procedures) between January 2000
      and December 2010 at the University Clinic of Navarra were analysed. The two
      groups displayed similar clinical characteristics. RESULTS: Patients submitted to
      laparoscopic liver resection (LLR) had a lower risk for complications [odds ratio
      (OR) = 0.24, 95% confidence interval (CI) 0.07-0.74; P = 0.013] and shorter
      hospital stay (OR = 0.08, 95% CI 0.02-0.27; P < 0.001) independently of the
      presence of classical risk factors for complications. In the cohort of patients
      with lesions involving posterosuperior liver segments (20 laparoscopic, 21 open
      procedures), LLR was associated with significantly fewer complications (OR =
      0.16, 95% CI 0.04-0.71) and a lower risk for a long hospital stay (OR = 0.1, 95%
      CI 0.02-0.43). CONCLUSIONS: This study confirms that the laparoscopic approach to
      hepatic resection decreases the risk for post-surgical complications and lengthy
      hospitalization in patients undergoing minor liver resections. This beneficial
      effect is observed even in patients with lesions located in segments that require
      technically difficult resections.

PMID- 24033490
TI  - Physicochemical and mechanical properties of zirconium oxide and niobium oxide
      modified Portland cement-based experimental endodontic sealers.
AB  - AIM: To evaluate the physicochemical and mechanical properties of Portland cement
      based experimental sealers (ES) with different radiopacifying agents (zirconium
      oxide and niobium oxide micro- and nanoparticles) in comparison with the
      following conventional sealers: AH Plus, MTA Fillapex and Sealapex. METHODOLOGY:
      The materials were tested for setting time, compressive strength, flow, film
      thickness, radiopacity, solubility, dimensional stability and formaldehyde
      release. Data were subjected to anova and Tukey tests (P < 0.05). RESULTS: MTA
      Fillapex had the shortest setting time and lowest compressive strength values (P
      < 0.05) compared with the other materials. The ES had flow values similar to the
      conventional materials, but higher film thickness (P < 0.05) and lower
      radiopacity (P < 0.05). Similarly to AH Plus, the ES were associated with
      dimensional expansion (P > 0.05) and lower solubility when compared with MTA
      Fillapex and Sealapex (P < 0.05). None of the endodontic sealers evaluated
      released formaldehyde after mixing. CONCLUSION: With the exception of
      radiopacity, the Portland cement-based experimental endodontic sealers presented
      physicochemical properties according to the specifications no 57 ANSI/ADA (ADA
      Professional Product Review, 2008) and ISO 6876 (Dentistry - Root Canal Sealing
      Materials, 2012, British Standards Institution, London, UK). The sealers had
      setting times and flow ability that was adequate for clinical use, satisfactory
      compressive strength and low solubility. Additional studies should be carried out
      with the purpose of decreasing the film thickness and to determine the ideal
      ratio of radiopacifying agents in Portland cement-based root canal sealers.

PMID- 24033491
TI  - Post-chemotherapy maturation in supratentorial primitive neuroectodermal tumors.
AB  - Maturation in central nervous system embryonal tumors is an uncommon phenomenon
      that is mainly reported in the context of specific histological subgroups of
      medulloblastoma. In this report we describe two cases of histological maturation
      in patients with supratentorial primitive neuroectodermal tumor with strikingly
      different outcomes. We discuss the potential impact of such findings on treatment
      and outcome. 

PMID- 24033492
TI  - Expression studies of six human obesity-related genes in seven tissues from
      divergent pig breeds.
AB  - Obesity has reached epidemic proportions globally and has become the cause of
      several major health risks worldwide. Presently, more than 100 loci have been
      related to obesity and metabolic traits in humans by genome-wide association
      studies. The complex genetic architecture behind obesity has triggered a need for
      the development of better animal models than rodents. The pig has emerged as a
      very promising biomedical model to study human obesity traits. In this study, we
      have characterized the expression patterns of six obesity-related genes, leptin
      (LEP), leptin receptor (LEPR), melanocortin 4 receptor (MC4R), fat mass and
      obesity associated (FTO), neuronal growth regulator 1 (NEGR)1 and adiponectin
      (ADIPOQ), in seven obesity-relevant tissues (liver; muscle; pancreas;
      hypothalamus; and retroperitoneal, subcutaneous and mesenteric adipose tissues)
      in two pig breeds (production pigs and Gottingen minipigs) that deviate
      phenotypically and genetically from each other with respect to obesity traits. We
      observe significant differential expression for LEP, LEPR and ADIPOQ in muscle
      and in all three adipose tissues. Interestingly, in pancreas, LEP expression is
      only detected in the fat minipigs. FTO shows significant differential expression
      in all tissues analyzed, and NEGR1 shows significant differential expression in
      muscle, pancreas, hypothalamus and subcutaneous adipose tissue. The MC4R
      transcript can be detected only in hypothalamus. In general, the expression
      profiles of the investigated genes are in accordance with those observed in human
      studies. Our study shows that both the differences between the investigated
      breeds and the phenotypic state with respect to obesity/leanness play a large
      role for differential expression of the obesity-related genes. 

PMID- 24033493
TI  - Nocturia Quality-of-Life questionnaire is a useful tool to predict nocturia and a
      risk of falling in Japanese outpatients: a cross-sectional survey.
AB  - OBJECTIVES: To evaluate the Japanese version of the Nocturia Quality-of-Life
      questionnaire for prediction of night-time voiding and risk of falling. METHODS:
      A survey was carried out from October 2008 to June 2009 in outpatients at 15
      general hospitals and 80 general clinics in Tochigi, Japan, using the Nocturia
      Quality-of-Life questionnaire, overactive bladder symptom score and self
      administered questionnaires on night-time symptoms (awakening, number of voids,
      incontinence and falling). RESULTS: The survey was completed by 2494 participants
      (1154 men, 1208 women; mean age 63.2 +/- 15.1 years). Overactive bladder was
      diagnosed in 625 participants (25.1%) according to the Japanese overactive
      bladder guideline using overactive bladder symptom score. Awakening during sleep
      was reported by 80.1% of the participants, and 70.4% awakened to go to the
      toilet. The mean Nocturia Quality-of-Life score was 86.8 +/- 16.9. The Nocturia
      Quality-of-Life score was lower in patients with overactive bladder, benign
      prostatic hyperplasia, diabetes, hypertension and cardiovascular diseases. The
      Nocturia Quality-of-Life score was significantly decreased in patients with night
      time symptoms (P < 0.001). Nocturia Quality-of-Life scores and those for
      subdomains were correlated with overactive bladder symptom score. Nocturia
      Quality-of-Life <=90 had 63.1% sensitivity and 78.6% specificity in indicating
      night-time voiding more than twice, and Nocturia Quality-of-Life questionnaire
      <=80 had 70.2% sensitivity and 79.5% specificity in indicating the probability of
      falling at least once. Logistic analysis showed that 10-year increase in age and
      overactive bladder in all participants were significant risk factors for Nocturia
      Quality-of-Life <=90. CONCLUSIONS: The Nocturia Quality-of-Life questionnaire
      represents a useful tool to predict nocturia and risk of falling in Japanese
      patients.

PMID- 24033494
TI  - Location and characterization of female germline stem cells (FGSCs) in juvenile
      porcine ovary.
AB  - OBJECTIVES: Existence of germline stem cells (GSCs) in juvenile mammalian female
      ovaries has been drastically debated recently since reports that adult mouse
      ovaries still have mitotically active germ cells have been proposed. In addition,
      definitive location of such female germline stem cells (FGSCs) had not been
      demonstrated. MATERIALS AND METHODS: We segregated porcine FGSCs mechanically
      from ovary cortex, and tested our hypotheses by utilizing immunofluorescent
      staining, qRT-PCR and western blotting. RESULTS: We attached emphasis to
      unambiguous location of FGSCs, which settle simultaneously in the theca.
      Dissected cells from porcine thecal layers maintained similar characteristics to
      mouse FGSCs and ESCs over 4-months in vitro culture. CONCLUSION: These results
      may provide a new resource for the study of oogenesis and therapy for ovarian
      sterility.

PMID- 24033495
TI  - Overall picture of an emerging neonatal infectious disease induced by a
      superantigenic exotoxin mainly produced by methicillin-resistant Staphylococcus
      aureus.
AB  - Since 1992, many neonates in neonatal intensive care units in Japan have been
      developing fever and systemic exanthema. Immunological analyses of neonates with
      these symptoms has revealed that the bacterial superantigen, toxic shock syndrome
      toxin-1 (TSST-1) is the cause. The name neonatal TSS-like exanthematous disease
      (NTED) has been applied to this condition. The most striking clinical finding has
      been that none of the term neonates have developed shock or died of NTED. The
      timing of NTED epidemics has coincided with the spread of emerging TSST-1
      producing methicillin-resistant Staphylococcus aureus clones in Japan. The low
      frequency of pregnant women with positive anti-TSST-1 antibody titers could be
      one reason for the spread of NTED in Japan. Neonates have immune tolerance
      against TSST-1 and may actively suppress the immune response to NTED with
      interleukin-10. According to the T cell responses in infants or young children
      with diseases induced by TSST-1, the pathophysiology of TSST-1-related diseases
      may be age-dependent. The precise mechanism of anergy and deletion of specific T
      cells stimulated with TSST-1 should be investigated in neonates infected with
      NTED. Both NTED and TSS might provide good models for analyzing the mechanism(s)
      of neonatal immune tolerance and the age-dependence of human immunity. This
      disease has not only become representative of diseases caused by superantigens,
      but has also yielded a considerable amount of evidence about human immune
      reactions against superantigens. 

PMID- 24033496
TI  - Histology of palate and soft palate tonsil of collared peccary (Tayassu tajacu).
AB  - Peccaries are characterized by a prominent skin gland, known as scent gland,
      which is located in the middle of the rump. These animals are able to survive in
      a great variety of habitats, from humid tropical forests to semi-arid areas. They
      are omnivorous animals, and their diet includes fibrous material, vegetables,
      fruits, small vertebrates and insects. Collared peccary hard palate and soft
      palate tonsils were studied, macroscopic morphometric data were collected and
      tissue samples were paraffin-embedded. Sections were stained with HE, Gomori's
      trichrome and von Kossa; the first two were used to study general organization
      and the latter to detect calcium deposits. The hard palate showed one incisive
      papilla followed by several rugae united by a distinct raphe. The hard palate is
      lined by a keratinised squamous epithelium resting on a dense connective, whereas
      in the soft palate, the epithelium is parakeratinised and showed lymphocyte
      infiltration. The palate showed several pacinian corpuscles in the propria
      submucosa. Two ovoid-shaped tonsils were found in the soft palate, and several
      crypts were observed on its surface. The epithelium was highly infiltrated by
      lymphocytes, and within the crypts, tonsilloliths were frequently observed. The
      study showed that the general organization of collared peccary palate is similar
      to other species, but in its oropharynx, only the soft palate tonsil was present
      and the pacinian corpuscles formed small aggregates. 

PMID- 24033497
TI  - The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) in the
      assessment of alcohol use disorders among acute injury patients.
AB  - BACKGROUND: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)
      is a brief alcohol screening test and a candidate for inclusion in recommended
      screening and brief intervention protocols for acute injury patients. The
      objective of the current study was to examine the performance of the AUDIT-C to
      risk stratify injury patients with regard to their probability of having an
      alcohol use disorder. METHODS: Participants (n = 1,004) were from a multisite
      Australian acute injury study. Stratum-specific likelihood ratio (SSLR) analysis
      was used to examine the performance of previously recommended AUDIT-C risk zones
      based on a dichotomous cut-point (0 to 3, 4 to 12) and risk zones derived from
      SSLR analysis to estimate the probability of a current alcohol use disorder.
      RESULTS: Almost a quarter (23%) of patients met criteria for a current alcohol
      use disorder. SSLR analysis identified multiple AUDIT-C risk zones (0 to 3, 4 to
      5, 6, 7 to 8, 9 to 12) with a wide range of posttest probabilities of alcohol use
      disorder, from 5 to 68%. The area under receiver operating characteristic curve
      (AUROC) score was 0.82 for the derived AUDIT-C zones and 0.70 for the recommended
      AUDIT-C zones. A comparison between AUROCs revealed that overall the derived
      zones performed significantly better than the recommended zones in being able to
      discriminate between patients with and without alcohol use disorder. CONCLUSIONS:
      The findings of SSLR analysis can be used to improve estimates of the probability
      of alcohol use disorder in acute injury patients based on AUDIT-C scores. In
      turn, this information can inform clinical interventions and the development of
      screening and intervention protocols in a range of settings.

PMID- 24033498
TI  - Predictors and outcomes of acyclovir-resistant herpes simplex virus infection
      among hematopoietic cell transplant recipients: case-case-control investigation.

PMID- 24033499
TI  - Design method of a foldable ventricular assist device for minimally invasive
      implantation.
AB  - To date, ventricular assist devices (VADs) have become accepted as a therapeutic
      solution for end-stage heart failure patients when a donor heart is not
      available. Newer generation VADs allow for a significant reduction in size and an
      improvement in reliability. However, the invasive implantation still limits this
      technology to critically ill patients. Recently, expandable/deployable devices
      have been investigated as a potential solution for minimally invasive insertion.
      Such a device can be inserted percutaneously via peripheral vessels in a
      collapsed form and operated in an expanded form at the desired location. A common
      structure of such foldable pumps comprises a memory alloy skeleton covered by
      flexible polyurethane material. The material properties allow elastic deformation
      to achieve the folded position and withstand the hydrodynamic forces during
      operation; however, determining the optimal geometry for such a structure is a
      complex challenge. The numerical finite element method (FEM) is widely used and
      provides accurate structural analysis, but computation time is considerably high
      during the initial design stage where various geometries need to be examined.
      This article details a simplified two-dimensional analytical method to estimate
      the mechanical stress and deformation of memory alloy skeletons. The method was
      applied in design examples including two popular types of blade skeletons of a
      foldable VAD. Furthermore, three force distributions were simulated to evaluate
      the strength of the structures under different loading conditions experienced
      during pump operation. The results were verified with FEM simulations. The
      proposed two-dimensional method gives a close stress and deformation estimation
      compared with three-dimensional FEM simulations. The results confirm the
      feasibility of such a simplified analytical approach to reveal priorities for
      structural optimization before time-consuming FEM simulations, providing an
      effective tool in the initial structural design stage of foldable minimally
      invasive VADs. 

PMID- 24033500
TI  - The relationship between complaints of night-time heartburn and sleep-related
      gastroesophageal reflux.
AB  - This study investigated whether the complaint of night-time heartburn (NHB) as
      opposed to daytime heartburn (DHB) is a reliable reflection of actual sleep
      related reflux events. Three groups of individuals were studied: individuals with
      complaints of NHB at least twice per week (n = 24), individuals with complaints
      of DHB (n = 23), and normal participants without any complaints of regular
      heartburn during the day or night (n = 25). All three groups were studied on one
      occasion with combined pH monitoring and polysomnography, and subjective
      questionnaires about sleep disturbance and sleep quality were given to all
      participants. The NHB group had significantly more sleep-related reflux events
      compared with both DHB and control groups (P < 0.01). DHB subjects had
      significantly (P < 0.05) more sleep-related reflux events than normal controls.
      Total acid contact time (ACT) was significantly (P < 0.05) elevated in the NHB
      group compared with both the DHB and control group. Sleep-related ACT was also
      significantly (P < 0.05) elevated in the NHB group compared with the other two
      groups, while upright (daytime) ACT was not significantly different. The NHB
      group was significantly (P < 0.05) worse regarding measures of both objective and
      subjective sleep quality. Subjects with exclusively DHB do have sleep-related
      reflux that is greater than normal controls. Subjects with NHB have significantly
      more sleep-related reflux, and both objective and subjective sleep abnormalities
      compared with normal controls. Complaints of NHB reflect sleep-related reflux
      events and may be indicative of a more clinically significant condition. 

PMID- 24033501
TI  - Follicular trachoma and trichiasis prevalence in an urban community in The
      Gambia, West Africa: is there a need to include urban areas in national trachoma
      surveillance?
AB  - OBJECTIVES: Urban areas are traditionally excluded from trachoma surveillance
      activities, but due to rapid expansion and population growth, the urban area of
      Brikama in The Gambia may be developing social problems that are known risk
      factors for trachoma. It is also a destination for many migrants who may be
      introducing active trachoma into the area. This study aimed to determine the
      prevalence and risk factors for follicular trachoma and trichiasis in Brikama.
      METHODS: A community-based cross-sectional prevalence survey including 27
      randomly selected households in 12 randomly selected enumeration areas (EAs) of
      Brikama. Selected households were offered eye examinations, and the severity of
      trachoma was graded according to WHO's simplified grading system. Risk factor
      data were collected from each household via a questionnaire. RESULTS: The overall
      prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9
      years was 3.8% (95% CI 2.5-5.6), and the overall prevalence of trichiasis in
      adults aged >=15 years was 0.46% (95% CI 0.17-1.14). EA prevalence of TF varied
      from 0% to 8.4%. The major risk factors for TF were dirty faces (P < 0.01, OR =
      9.23, 95% CI 1.97-43.23), nasal discharge (P = 0.039, OR = 5.11, 95% CI 1.08
      24.10) and residency in Brikama for <1 year (P = 0.047, OR = 7.78, 95% CI 1.03
      59.03). CONCLUSIONS: Follicular trachoma can be considered to have been
      eliminated as a public health problem in Brikama according to WHO criteria.
      However, as the prevalence in some EAs is >5%, it may be prudent to include
      Brikama in surveillance programmes. Trichiasis remains a public health problem
      (>0.1%), and active case finding needs to be undertaken.

PMID- 24033502
TI  - Familial short stature is associated with a novel dominant-negative heterozygous
      insulin-like growth factor 1 receptor (IGF1R) mutation.

PMID- 24033503
TI  - Temporal analysis of genetic structure to assess population dynamics of
      reintroduced swift foxes.
AB  - Reintroductions are increasingly used to reestablish species, but a paucity of
      long-term postrelease monitoring has limited understanding of whether and when
      viable populations subsequently persist. We conducted temporal genetic analyses
      of reintroduced populations of swift foxes (Vulpes velox) in Canada (Alberta and
      Saskatchewan) and the United States (Montana). We used samples collected 4 years
      apart, 17 years from the initiation of the reintroduction, and 3 years after the
      conclusion of releases. To assess program success, we genotyped 304 hair samples,
      subsampled from the known range in 2000 and 2001, and 2005 and 2006, at 7
      microsatellite loci. We compared diversity, effective population size, and
      genetic connectivity over time in each population. Diversity remained stable over
      time and there was evidence of increasing effective population size. We
      determined population structure in both periods after correcting for differences
      in sample sizes. The geographic distribution of these populations roughly
      corresponded with the original release locations, which suggests the release
      sites had residual effects on the population structure. However, given that both
      reintroduction sites had similar source populations, habitat fragmentation, due
      to cropland, may be associated with the population structure we found. Although
      our results indicate growing, stable populations, future connectivity analyses
      are warranted to ensure both populations are not subject to negative small
      population effects. Our results demonstrate the importance of multiple sampling
      years to fully capture population dynamics of reintroduced populations. Analisis
      Temporal de la Estructura Genetica para Evaluar la Dinamica Poblacional de Zorros
      (Vulpes velox) Reintroducidos. 

PMID- 24033504
TI  - Effect of clenbuterol on tracheal mucociliary transport in horses undergoing
      simulated long-distance transportation.
AB  - BACKGROUND: Pneumonia is observed in horses after long-distance transportation in
      association with confinement of head position leading to reduction in tracheal
      mucociliary clearance rate (TMCR). HYPOTHESIS/OBJECTIVES: Clenbuterol, a beta-2
      agonist shown to increase TMCR in the horse, will ameliorate the effects of a
      fixed elevated head position on large airway contamination and inflammation in a
      model of long-distance transportation model. ANIMALS: Six adult horses. METHODS:
      A cross-over designed prospective study. Horses were maintained with a fixed
      elevated head position for 48 hours to simulate long-distance transport, and
      treated with clenbuterol (0.8 MUg/kg PO q12h) or a placebo starting 12 hours
      before simulated transportation. TMCR was measured using a charcoal clearance
      technique. Data were collected at baseline and 48 hours, and included TMCR,
      tracheal wash cytology and quantitative culture, rectal temperature, CBC,
      fibrinogen, and serum TNFalpha, IL-10, and IL-2 levels. There was a 18-21 day
      washout between study arms, and data were analyzed using regression analysis and
      Wilcoxon rank-sum tests. RESULTS: Tracheal mucociliary clearance rate was
      significantly decreased after transportation in both treatment (P = .002) and
      placebo (P = .03) groups. There was a significant effect of treatment on TMCR,
      with the treatment group showing half the reduction in TMCR compared with the
      placebo group (P = .002). Other significant differences between before- and after
      transportation samples occurred for serum fibrinogen, peripheral eosinophil
      count, quantitative culture, tracheal bacteria, and degenerate neutrophils,
      though no treatment effect was found. CONCLUSIONS AND CLINICAL IMPORTANCE:
      Treatment with clenbuterol modestly attenuates the deleterious effects of this
      long-distance transportation model on tracheal mucociliary clearance.

PMID- 24033505
TI  - Neural correlates of nondual awareness in meditation.
AB  - Dualities such as self versus other, good versus bad, and in-group versus out
      group are pervasive features of human experience, structuring the majority of
      cognitive and affective processes. Yet, an entirely different way of
      experiencing, one in which such dualities are relaxed rather than fortified, is
      also available. It depends on recognizing, within the stream of our
      consciousness, the nondual awareness (NDA)--a background awareness that precedes
      conceptualization and intention and that can contextualize various perceptual,
      affective, or cognitive contents without fragmenting the field of experience into
      habitual dualities. This paper introduces NDA as experienced in Tibetan Buddhist
      meditation and reviews the results of our study on the influence of NDA on
      anticorrelated intrinsic and extrinsic networks in the brain. Also discussed are
      preliminary data from a current study of NDA with minimized phenomenal content
      that points to involvement of a precuneus network in NDA.

PMID- 24033506
TI  - Dietary competition between the alien Asian Musk Shrew (Suncus murinus) and a re
      introduced population of Telfair's Skink (Leiolopisma telfairii).
AB  - Re-introduction of rare species to parts of their historical range is becoming
      increasingly important as a conservation strategy. Telfair's Skinks (Leiolopisma
      telfairii), once widespread on Mauritius, were until recently found only on Round
      Island. There it is vulnerable to stochastic events, including the introduction
      of alien predators that may either prey upon it or compete for food resources.
      Consequently, skinks have been introduced to Ile aux Aigrettes, another small
      Mauritian island that has been cleared of rats. However, the island has been
      invaded by Asian Musk Shrews (Suncus murinus), a commensal species spread by man
      well beyond its natural Asian range. Our aim was to use next-generation
      sequencing to analyse the diets of the shrews and skinks to look for niche
      competition. DNA was extracted from skink faeces and from the stomach contents of
      shrews. Application of shrew- and skink-specific primers revealed no mutual
      predation. The DNA was then amplified using general invertebrate primers with
      tags to identify individual predators, and then sequenced by 454 pyrosequencing.
      119 prey MOTUs (molecular taxonomic units) were isolated, although none could be
      identified to species. Seeding of cladograms with known sequences allowed higher
      taxonomic assignments in some cases. Although most MOTUs were not shared by
      shrews and skinks, Pianka's niche overlap test showed significant prey overlap,
      suggesting potentially strong competition where food resources are limited. These
      results suggest that removal of the shrews from the island should remain a
      priority. 

PMID- 24033507
TI  - Kidney regeneration by non-platelet RNA-containing particle-derived cells.
AB  - We found a group of non-platelet RNA-containing particles (NPRCPs) in human
      umbilical cord blood. These particles can aggregate, fuse and become non
      nucleated cells when cocultured with nucleated cells in vitro. The non-nucleated
      cells further differentiate into nucleated cells expressing octamer binding
      transcription factor 4 (OCT4). The NPRCPs are approximately 1-5 MUm in diameter,
      have a thin bilayer membrane, contain short RNAs and microRNAs and express OCT4,
      sex-determining region Y 2 (SOX2) and DEAD box polypeptide 4 (DDX4). To confirm
      the function of NPRCPs in vivo, we examined the effects of tail vein-injected
      green fluorescent protein (GFP)-labelled NPRCPs on mouse kidneys damaged by prior
      ischaemia and reperfusion from Day 1 to Week 6. Within 1 day of injection of
      NPRCPs, immunofluorescence and immunohistochemistry revealed a large number of
      extravasated NPRCPs in the renal calyces, damaged glomeruli and duct tubules.
      During the course of regeneration, NPRCPs fused into large, non-nucleated
      cellular structures that further became large nucleated cells to regenerate
      multicellular kidney tubules. In addition, many NPRCPs became tiny nucleated
      cellular structures that further differentiated into interstitial cells in
      connective tissue. The extravasated NPRCPs also arranged themselves into non-cell
      glomerular structures before further regenerating into nucleated cells of the
      glomerulus. In conclusion, the results demonstrate that, via different patterns
      of differentiation, NPRCP-derived cells can regenerate mouse kidney tissue
      damaged by ischaemia.

PMID- 24033508
TI  - Age-dependent baseline values of faecal cortisol metabolites in the American mink
      (Neovison vison) under semi-natural housing conditions.
AB  - The welfare of an animal is ensured if it is able to fully satisfy its essential
      species-typical needs in all functional aspects of behaviour. In mink,
      stereotypies and apathy, internal and/or external injuries as well as increased
      susceptibility to disease have been known to occur as a result of chronic stress.
      The non-invasive method of analysing faecal cortisol metabolites (FCM) allows
      conclusions to be drawn about the stress level in the respective housing system.
      The objective of this study is to find out how the cortisol metabolites content
      in the faecal changes with increasing age of the mink under semi-natural housing
      conditions. Thus, 40 American mink (Neovison vison) were housed in two outdoor
      enclosures imitating natural conditions. Throughout the entire study (13th to
      32nd week of life), faecal samples were collected to measure cortisol
      metabolites. No differences in FCM concentrations between the two outdoor
      enclosures were found. In the young mink lower, less fluctuating FCM levels were
      found than in older animals. After the first faecal collection in the 13th/14th
      week of life, the level of metabolites decreased slightly (p = 0.032; 17th/18th
      week). From the 22nd/23rd week onwards until the 30th/31st week, shortly before
      the animals were pelted, continuously increasing concentrations were then
      measured. Increasing FCM levels with advancing age of the animals are probably
      attributable to the onset of sexual maturity and/or the respective season. This
      has to be taken into account in future studies using this method for assessing
      welfare and when comparing different mink housing systems.

PMID- 24033509
TI  - Horse-, rider-, venue- and environment-related risk factors for elimination from
      Federation Equestre Internationale endurance rides due to lameness and metabolic
      reasons.
AB  - REASONS FOR PERFORMING THE STUDY: There is limited information on risk factors
      for elimination from endurance rides. OBJECTIVES: To assess risk factors for
      elimination for lameness and metabolic reasons from Federation Equestre
      Internationale (FEI) endurance rides of 80-160 km distance. STUDY DESIGN:
      Unmatched case-control. METHODS: Venue-, horse- and rider-related data were
      collected from the FEI website. Data on weather conditions and terrain were
      collected at the venue. Univariable and multivariable logistic regression
      analyses were used to assess risk factors for elimination for lameness and
      metabolic reasons, respectively. RESULTS: Multivariable logistic regression on
      1435 horse starts revealed that the venue was significantly associated with
      elimination for lameness (P = 0.013). The horse's previous experience at a
      greater distance than the current ride (odds ratio [OR] = 0.82, 95% confidence
      interval [CI] 0.71-0.95, P = 0.008) and > 90 days elapsed since the last FEI ride
      (OR = 0.78, 95% CI 0.62-0.99, P = 0.044) significantly reduced the risk of
      elimination for lameness. In the multivariable model for elimination for
      metabolic reasons, the venue (P = 0.011), increasing number of started horses (OR
      = 1.008, 95% CI 1.00-1.01, P = 0.001) and deep sand or soil on the track (OR =
      1.98, 95% CI 1.17-3.35, P = 0.001) significantly increased the risk of
      elimination for metabolic reasons. CONCLUSIONS: Reducing the frequency of racing
      may contribute to decreased risk of elimination for lameness. Competing in deep
      sand or soil may contribute to exhaustion, leading to elimination for metabolic
      reasons. Eliminations are likely to be the end result of a complex process, and
      not every aspect was or can be measured. Further studies with a larger number of
      horse starts and assessment of variables that could not be measured in this study
      may identify additional risk factors that can be modified.

PMID- 24033510
TI  - Influence of the exposure of MTA with and without calcium chloride to phosphate
      buffered saline on the push-out bond strength to dentine.
AB  - AIM: To analyse the influence of exposure of mineral trioxide aggregate (MTA)
      with and without calcium chloride (CaCl2 ) to phosphate-buffered saline (PBS) on
      the push-out bond strength, over different experimental periods. METHODOLOGY: One
      hundred and twenty dentine discs with standardized cavities were filled with MTA
      with and without 10% CaCl2 . The specimens were randomly divided as follows (n =
      30): (G1) MTA in contact with a moistened cotton pellet, (G2) MTA immersed in
      PBS, (G3) MTA + CaCl2 in contact with a moistened cotton pellet and (G4) MTA +
      CaCl2 immersed in PBS. The samples were stored for 3, 28 and 60 days. The bond
      strengths were measured with the Instron Testing machine. Data were analysed
      using the three-way anova and Tukey test (P < 0.05). RESULTS: In general, the
      samples of MTA with and without CaCl2 , exposed to PBS, had higher bond strength
      values in all study periods (P < 0.05). Analysis of the influence of addition of
      CaCl2 to MTA (G1 * G3) evidenced significant differences in bond strength in the
      different periods (P < 0.05). CONCLUSIONS: The exposure of MTA to PBS positively
      influenced the push-out bond strength, whereas the addition of CaCl2 had a
      negative influence.

PMID- 24033511
TI  - Dual input control: activation of the Bartonella henselae VirB/D4 type IV
      secretion system by the stringent sigma factor RpoH1 and the BatR/BatS two
      component system.
AB  - The co-ordinated expression of virulence factors is a critical process for any
      bacterial pathogen to colonize its host. Here we investigated the mechanisms of
      niche adaptation of the zoonotic pathogen Bartonella henselae by combining
      genetic approaches and shotgun proteomics. We demonstrated that expression of the
      VirB/D4 type IV secretion system (T4SS) and its secreted effector proteins
      require the alternative sigma factor RpoH1, which levels are controlled by the
      stringent response (SR) components DksA and SpoT. The RpoH1-dependent activation
      requires an active BatR/BatS two-component system (TCS) while BatR expression is
      controlled by RpoH1 and the SR components. Deletion of spoT results in a strong
      attenuation of VirB/D4 T4SS expression whereas dksA, rpoH1 or batR deletion fully
      abolishes its activity. In contrast to their activating effect on the VirB/D4
      T4SS, which is critical at the early stage of host infection, SpoT and DksA
      negatively regulate the Trw T4SS, which mediates host-specific erythrocyte
      infection at a later stage of the colonization process. Our findings support a
      model where the SR signalling and the physiological pH-induced BatR/BatS TCS
      conjointly control the spatiotemporal expression of B. henselae adaptation
      factors during host infection. 

PMID- 24033512
TI  - Fertility outcomes of patients with early stage endometrial carcinoma.
AB  - AIM: Three to five percent of endometrial carcinoma patients are younger than 40
      years and may desire fertility. Conservative treatment can be employed in these
      cases. We aimed to review treatment outcomes of patients who were diagnosed with
      endometrial carcinoma and who wanted to preserve their fertility. MATERIAL AND
      METHODS: We reviewed nine patients who were diagnosed with early stage
      endometrial carcinoma and wanted to spare their fertility. The patients were
      followed up at Baskent University Adana Research Center from January 2004 to
      December 2011. RESULTS: In all patients the carcinoma presented as polyps, which
      were resected by hysteroscopy. After being informed about both surgical and
      medical therapies, four patients preferred surgery and five preferred medical
      treatment. The mean number of in vitro fertilization trials after conservative
      treatment was 3.25. One woman, who was on medroxyprogesterone acetate, delivered
      a healthy term baby from a fresh cycle. Another woman, who was on dydrogesterone,
      got pregnant from a thawing cycle, which later ended up in a missed abortus. Of
      all the patients who chose medical treatment, three had surgery at the end. One
      woman developed an ovarian tumor during the follow-up; one woman had a recurrence
      of endometrial carcinoma on dilatation and curettage for missed abortus and one
      woman tried in vitro fertilization several times and could not get pregnant, thus
      decided to have surgery. Two women had stage IA endometrial carcinoma and one had
      stage IIB ovarian carcinoma. CONCLUSION: Conservative treatment of endometrial
      carcinoma is safe in most cases. However, patients should be well-informed about
      the risks of conservative treatment because delaying definitive treatment
      sometimes worsens the prognosis.

PMID- 24033513
TI  - Optimal immunity meets natural variation: the evolutionary biology of host
      defence.
AB  - This editorial introduces the seven articles that comprise the Parasite
      Immunology special issue on the Evolutionary Biology of Host Defence. The
      rationale for an evolutionary approach to immunoparasitology is briefly outlined,
      and then the articles are placed in that broader context. A central aim of each
      article is to explain the generation and maintenance of immunological
      heterogeneity among hosts in nature. The authors describe new tools and
      approaches that enable unprecedented insight into evolutionary and immunological
      processes in both the laboratory and the wild. The examples discussed include
      insects, birds and mammals (as hosts) and trypanosomes, apicomplexans and
      nematodes (as parasites).

PMID- 24033514
TI  - Predictors of morbidity and mortality after hepatectomy in elderly patients:
      analysis of 7621 NSQIP patients.
AB  - OBJECTIVES: Increasingly, surgeons are performing hepatectomies in older
      patients. This study was designed to analyse the incidences of and risk factors
      for post-hepatectomy morbidity and mortality in elderly patients. METHODS: All
      elective hepatectomies for the period 2005-2010 recorded in the American College
      of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database
      were evaluated. Factors associated with 30-day rates of morbidity and mortality
      were compared between patients aged >=75 years and those aged <75 years. RESULTS:
      Elderly patients accounted for 894 of 7621 (11.7%) hepatectomies. These patients
      more frequently had comorbidities (diabetes, cardiovascular or lung disease,
      lower albumin, elevated creatinine, anaesthesia risk; all P < 0.05) and were more
      likely to undergo partial or left rather than right or extended hepatectomies (P
      = 0.013). Despite the lesser surgical magnitude of these procedures, elderly
      patients experienced higher rates of severe complications (23.9% versus 18.4%; P
      < 0.001) and overall postoperative mortality (4.8% versus 2.0%; P < 0.001). The
      occurrence of any severe complication was associated with a mortality rate of
      20.1% in elderly patients and 10.8% in non-elderly patients (P < 0.001). This
      disparity in mortality was more pronounced in patients with two or more (31.7%
      versus 20.2%; P < 0.001) and three or more (46.3% versus 31.1%; P < 0.001) severe
      complications. Independent risk factors for severe complications and/or mortality
      included an albumin level of < 4 g/dl, lung disease, intraoperative transfusion,
      a concurrent intra-abdominal operation, and an operative time of >240 min (all P
      < 0.05). CONCLUSIONS: Given their lower physiologic reserve, elderly patients are
      at much greater risk for mortality after severe complications. To improve
      outcomes, surgeons should balance age and preoperative comorbidities with
      magnitude of hepatectomy.

PMID- 24033515
TI  - Emphysematous pyelonephritis: clinical characteristics and prognostic factors.
AB  - OBJECTIVES: Emphysematous pyelonephritis is a severe necrotizing infection of the
      renal parenchyma and perirenal tissues that is caused by gas-producing bacterial
      pathogens. The aim of the present study was to determine the clinical
      characteristics and prognostic factors of patients with emphysematous
      pyelonephritis. METHODS: We retrospectively analyzed the clinical and laboratory
      data, imaging findings, and outcomes of 32 patients with emphysematous
      pyelonephritis. Receiver operating characteristic curve analysis was carried out
      on variables that were significantly associated with patient mortality. RESULTS:
      The overall survival rate was 87.5% (28/32). Escherichia coli (43.6%) was the
      most common organism cultured from urine and blood specimens. Hypoalbuminemia,
      shock as the presenting feature, bacteremia, need for hemodialysis and
      polymicrobial infection were significantly more common in cases resulting in
      death. The area under the receiver operating characteristic curve was 0.96. The
      cut-off point determined by the maximum Youden index (0.93) for three of these
      five factors yielded a sensitivity of 1.00 and specificity of 0.93. Shock as an
      initial presentation (P = 0.039) and polymicrobial infection (P = 0.010) were
      significantly associated with poor outcome. There were no significant differences
      in the clinical or laboratory features of the patients who did or did not undergo
      nephrectomy. CONCLUSION: Hypoalbuminemia, shock as an initial presentation,
      bacteremia, indications for hemodialysis and polymicrobial infection represent
      prognostic factors for mortality in patients with emphysematous pyelonephritis.
      Patients presenting with more than two of these prognostic factors carry the
      highest risk of mortality, and they require timely diagnosis and aggressive
      management.

PMID- 24033516
TI  - Measurements of semi-volatile organic compounds in settled dust: influence of
      storage temperature and duration.
AB  - Indoor dust samples cannot always be analyzed immediately after collection.
      However, little information is currently available on how storage conditions may
      affect measurements. This study was designed to determine how sample storage
      conditions may affect the concentration of semi-volatile organic compounds
      (SVOCs) in the dust. A composite dust was prepared using a Standard Reference
      Material (SRM 2585) with real indoor dust samples. The composite dust was stored
      in various types of packaging, at different temperatures (-18 degrees C, 5
      degrees C, 20 degrees C, and 35 degrees C), and in different light conditions.
      The concentration of SVOCs was measured after various storage durations. No
      effect on SVOC concentrations was observed for the composite dust stored in an
      amber glass vial at -18 degrees C for 36 months. At 5 degrees C, 20 degrees C,
      and 35 degrees C, losses occurred for the more volatile compounds. The
      experimental storage conditions clearly showed that temperature and duration
      affected the concentrations of SVOCs in the composite dust. The type of packaging
      material (polyethylene zip bag or polyethylene garbage bag) did not seem to have
      a systematic effect on the preservation of SVOCs in the composite dust. Maximum
      storage duration times are proposed for each compound at various temperatures.
      For most compounds, samples can be stored for 2 months at 20 degrees C. For
      samples that cannot be analyzed immediately, we recommend to store them in the
      dark at -18 degrees C to ensure a good recovery of all tested compounds. 

PMID- 24033517
TI  - Validation of a single-nucleotide polymorphism panel for parentage testing of
      farmed red deer.
AB  - Red deer behaviour prevents the accurate physical matching of dams to fawns and,
      therefore, breeders have to rely on DNA-based parentage testing. A panel
      consisting of 100 single nucleotide polymorphism markers, with an average minor
      allele frequency of 0.25, was able to resolve 92% of fawns to both parents. In
      comparison, an existing 12-marker microsatellite panel was able to resolve 68% of
      fawns to both parents. When excluding dam DNA information, the single nucleotide
      polymorphism panel matched 81% of the fawns to their sires and the microsatellite
      panel 71%. 

PMID- 24033518
TI  - A primary health care strategic framework.

PMID- 24033519
TI  - Comprehensive picture of rural women's needs in maternity care in Tasmania,
      Australia.
AB  - OBJECTIVE: This study investigates (i) rural women's needs in maternity care in
      Tasmania; (ii) the current rural maternity services in Tasmania; and (iii) the
      gap between women's needs and the services provided. DESIGN: Mixed methods study
      was adopted. A questionnaire explored women's views on rural maternity services
      from antenatal to postnatal care and also invited comments from the participants.
      Interviews were conducted to provide comprehensive insights into their needs in
      maternity care. SETTING: Six rural communities in Tasmania, Australia.
      PARTICIPANTS: Women who have had childbirth experiences in rural areas in
      Tasmania. RESULTS: Two hundred ten women completed the questionnaire with a
      response rate of 35%. There were over 150 written comments from the survey.
      Twenty-two follow-up interviews were conducted. This paper reports the written
      comments from the survey and interviews. Five main themes emerged from the data,
      namely (i) access needs, (ii) safety needs, (iii) needs for rural birthing
      services, (iv) support needs and (v) needs for quality services. CONCLUSION: This
      study has revealed a comprehensive picture of rural women's needs in maternity
      care throughout their pregnancy to the early postnatal period. There is a major
      lack of maternity services in rural areas of Tasmania. The lack of rural
      maternity services shifts cost and risk from the health care system to rural
      women and their families. Women want to have greater access to maternity services
      in their local community and be ensured safety for themselves and their babies.
      Moreover, they need more support from the health care system and they desire
      quality services.

PMID- 24033520
TI  - Recombinant tissue plasminogen activator (rt-PA) utilisation by rural clinicians
      in acute ischaemic stroke: an audit of current practice and clinical outcomes.
AB  - OBJECTIVE: This audit of activity reports on current rates of recombinant tissue
      plasminogen activator (rt-PA) use within specialised stroke care units in rural
      New South Wales (NSW). It measures stroke onset-to-treatment time and morbidity
      outcomes for patients treated with rt-PA and aims to establish the safety and
      effectiveness of rt-PA use in rural NSW. DESIGN, SETTING AND PARTICIPANTS:
      Medical records reviews of patients admitted with acute ischaemic stroke at two
      rural NSW hospitals between 1 July 2008 and 30 June 2010. MAIN OUTCOME MEASURES:
      Treatment with rt-PA, morbidity scores 5 days post-stroke or discharge, incidence
      of intracranial haemorrhage and mortality rate 6 months post-stroke were
      recorded. Treatment protocol violations were assessed and time to treatment from
      stroke onset and hospital admission. RESULTS: Of 605 patients admitted with acute
      ischaemic stroke, 20 (3.3%) received rt-PA treatment. Of these two, 10% had
      symptomatic intracranial haemorrhage and one died within 6 months. Morbidity
      scores for those treated with rt-PA were similar to those not treated. The median
      onset-to-needle time was 2 hours and 34 min, and the median door-to-needle time
      was 1 hour and 40 min. There were no treatment protocol violations. CONCLUSION:
      Recombinant tissue plasminogen activator can be delivered in rural Australian
      hospitals in a timely manner within recommended implementation guidelines. Acute
      stroke thrombolytic services in rural Australian facilities had comparable
      outcomes to metropolitan facilities. Small numbers of thrombolysed patients
      prevented a validation study of the well-defined outcome benefits from rt-PA. The
      need for ongoing data collection in regional settings is supported.

PMID- 24033521
TI  - Characteristics of rural hospital services for people with dementia: findings
      from the Hospital Dementia Services Project.
AB  - OBJECTIVE: To obtain information about aged care services in rural New South
      Wales public hospitals, and to describe key operational aspects of their service
      delivery models. DESIGN: A mixed methods design was used to combine data
      collected from: (i) a survey of public hospitals and (ii) qualitative site visits
      in a sample of eleven rural sites. SETTING: Rural public hospitals in NSW,
      Australia. PARTICIPANTS: Qualitative data were collected from multidisciplinary
      clinicians, managers and community service providers who participated in site
      visits in 2010 and from surveys of NSW public hospitals in 2009/10 about aged
      care and dementia services. RESULTS: Survey and site visit findings demonstrated
      that rural hospitals have fewer secure beds for managing patients with disturbed
      behaviour due to dementia and delirium and fewer speciality aged care staff than
      metropolitan hospitals. Site visit participants also described how secure
      environments can aid care for people with dementia even in the absence of
      clinical specialists. CONCLUSION: The care of people with dementia in rural
      hospitals is constrained by access to specialist aged care staff and the physical
      environment of the hospital. Clinicians are adept at maximising resources to
      manage diagnosis and transitions for people with dementia. Further understanding
      of how key operational aspects of clinical leadership and environmental
      modifications impact on a range of patient outcomes would be valuable.

PMID- 24033522
TI  - They've given me that many tablets, I'm bushed. I don't know where I'm going:
      Aboriginal and Torres Strait Islander peoples' experiences with medicines.
AB  - OBJECTIVE: To explore Aboriginal and Torres Strait Islander patients' experiences
      with medicines and the barriers and facilitators to their effective use of
      medicines. DESIGN: A descriptive, qualitative study, using 18 semi-structured
      focus groups with 101 Aboriginal and Torres Strait participants. Groups were
      conducted at 11 Aboriginal health services. These were recorded, transcribed and
      a thematic analysis was performed. SETTINGS AND PARTICIPANTS: Participants were
      Aboriginal and Torres Strait Islander patients, taking multiple medicines, who
      attended Aboriginal health services (AHSs) and who spoke English. AHSs varied in
      governance, size and service delivery models as well as their locations which
      were across urban, regional, rural and remote settings. RESULTS: Major themes
      identified were consistent across all settings and patients. These were confusion
      over medicines, perceived lack of advice from health professionals to patients
      about medicines and challenges in having effective interactions with medical
      practitioners and pharmacists. Participants wanted more information about
      medicine, indications for medicine, how they should be used, potential side
      effects, drug interactions and duration of therapy. They also reported an absence
      of appropriate medication labelling and written information. CONCLUSION: Many
      Aboriginal and Torres Strait Islander patients take multiple medicines and often
      find managing their medicines difficult and worrying. These patients require more
      comprehensive information, verbal and written, and more effective communications
      from doctors and pharmacists about medication indications, mechanisms, side
      effects, drug interactions and duration of treatment. Pharmacists have an
      opportunity to play a greater role in improving understanding of medicines and
      treatment choices.

PMID- 24033523
TI  - Safe play areas on farms in New South Wales.
AB  - OBJECTIVE: To assess the prevalence and security of fenced house yards on NSW
      farms and rural properties with a view to providing information to increase the
      development of safe play areas on farms. DESIGN: A cross-sectional stratified
      study using computer-assisted telephone interviewing. SETTING: Interviews were
      conducted in the four rural Area Health Services throughout February to December
      2008. PARTICIPANTS: Randomly selected sample of 1117 adults living on a farm or
      rural property in the study areas. MAIN OUTCOME MEASURES: Self-reported issues
      involving fenced house yards or safe play areas for children. RESULTS: Overall,
      79.8% of farm respondents reported that they had a fenced house yard or safe play
      area. For those respondents with a fenced house yard, 66.6% reported that it was
      secure enough to prevent /make it difficult for a young child to wander away
      unsupervised. Based on these figures, it is estimated that only 53.1% of all
      farms or rural properties have a secure fenced house yard or safe play area.
      There were statistically significant variations between geographic locations,
      with the North Coast (37.7%) being lower. CONCLUSIONS: This study illustrates a
      need across rural NSW to further promote, install or upgrade secure fenced house
      yards or safe play areas. While all geographic regions of the state could improve
      provision to protect children, there may also be some that are in need of more
      intensive intervention programs to enhance compliance. Such a proposition may
      also be relevant on a national level.

PMID- 24033524
TI  - Job stress and burnout among urban and rural hospital physicians in Japan.
AB  - OBJECTIVE: To elucidate the differences in job stress and burnout status of
      Japanese hospital physicians between large cities, small cities, and towns and
      villages. DESIGN: Cross-sectional study. SETTING: Postal self-administered
      questionnaires were distributed to 2937 alumni of Asahikawa Medical University.
      PARTICIPANTS: Four hundred and twenty-two hospital physicians. MAIN OUTCOME
      MEASURES: The Brief Job Stress Questionnaire was used to evaluate job demand, job
      control and social support. The Japanese version of the Maslach Burnout Inventory
      General Survey (MBI-GS) was used to evaluate burnout. An analysis of covariance
      was conducted on the mean scores on the Brief Job Stress Questionnaire and the
      MBI-GS scales after adjusting for sex, age and specialties. RESULTS: In adjusted
      analyses, the job demand score was significantly different among physicians in
      the three areas. In Bonferroni post-hoc tests, scores in large cities was
      significantly higher than those in small cities and towns and villages. The job
      control score showed a significant difference and a marginally significant trend,
      with large cities associated with lower job control. There were significant
      differences in support from supervisors and that from family/friends, and scores
      in large cities was significantly higher than those in small cities in the post
      hoc test. There was a significant effect on the exhaustion scale of the MBI-GS,
      with large cities associated with higher exhaustion, and scores in large cities
      was significantly higher than those in small cities. CONCLUSIONS: Urban hospital
      physicians had more job demand, less job control and exhaustion caused by
      burnout, and rural hospital physicians had less social support.

PMID- 24033525
TI  - Health outcomes of eating disorder clients in a rural setting.

PMID- 24033526
TI  - Perceptions of body satisfaction and desired weight loss among Tasmanian
      adolescents.

PMID- 24033527
TI  - Retention of allied health professionals in Tasmania.

PMID- 24033528
TI  - How can you help to close the gap?

PMID- 24033529
TI  - The relationship between excessive alcohol consumption and alcohol use disorders
      according to DSM-IV and DSM-5.
AB  - BACKGROUND: Although it seems intuitive that alcohol use disorders (AUDs) include
      excessive alcohol consumption (EAC), this notion is not well established. This
      study investigates to which degree EAC (defined as >14/21 drinks weekly for
      women/men and at least three 5+ drinking days per week) and AUD overlap and
      whether problematic alcohol use groups (EAC-only, AUD-only, and EAC + AUD) differ
      from each other and from nonproblematic alcohol users regarding
      sociodemographics, mental health problems, functioning, and service utilization.
      METHODS: Data were derived from the Netherlands Mental Health Survey and
      Incidence Study-2, a population-based study including 5,443 current drinkers
      (aged 18 to 64) interviewed with the Composite International Diagnostic Interview
      3.0. Both DSM-IV AUDs and a proxy of DSM-5 AUD are considered. RESULTS: Of the
      current drinkers, 3.8% reported 12-month EAC. Twelve-month prevalence of DSM-IV
      and DSM-5 AUD were 5.4 and 4.4%, respectively. Regarding DSM-IV, only 17.7% of
      subjects with AUD reported EAC and 25.3% of those with EAC had an AUD. Compared
      with nonproblematic alcohol users, the 3 groups of problematic alcohol use (EAC
      only, AUD-only, and EAC + AUD) were more often associated with mental health
      problems, poorer functioning, and service utilization. There were few differences
      between EAC-only and AUD-only regarding these correlates. However, EAC + AUD had
      strongest associations with above-mentioned correlates compared with the other 3
      groups. Compared with DSM-IV findings, DSM-5 AUDs had slightly larger overlap
      with EAC, but correlates were similarly associated with problematic alcohol use
      groups. CONCLUSIONS: Findings indicate limited overlap between EAC and AUD. Yet,
      both dimensions were similarly associated with other problems suggesting that
      both should be included in future epidemiological research to detect the total
      group of problematic alcohol users.

PMID- 24033530
TI  - Low molecular weight heparin dosing and monitoring in solid organ transplant
      recipients.
AB  - Anti-Xa monitoring for low molecular weight heparin (LMWH) is currently
      recommended in obese, renally impaired, and pregnant patients. Substantial
      evidence indicates that solid organ transplant (SOT) patients are at an increased
      risk of renal impairment, thus representing a population at risk of LMWH
      accumulation. The purpose of this study was to review our experience with LMWH
      dosing and monitoring in a cohort of transplant recipients. This was a
      retrospective, single-center review of 96 SOT patients receiving enoxaparin
      treatment and anti-Xa monitoring. The percent of patients with supratherapeutic
      anti-Xas (>1 IU/mL) was determined, as was the relationship between enoxaparin
      dosages and anti-Xa levels and bleeding. The cohort had a mean age of 62 yr and
      creatinine clearance of 59 mL/min and was primarily lung transplant recipients
      (73%). The mean enoxaparin dose was 0.82 mg/kg, which resulted in a mean anti-Xa
      level of 0.98 IU/mL. Despite the reduced enoxaparin dose, 44% of patients
      experienced a supratherapeutic anti-Xa level. Patients with supratherapeutic anti
      Xas had higher doses than those within the therapeutic range (0.89 mg/kg vs. 0.77
      mg/kg; p = 0.002). No major bleeds occurred. Supratherapeutic anti-Xa levels are
      common in transplant patients receiving enoxaparin therapy. Empirically reduced
      dosing of enoxaparin and monitoring may warrant consideration in this population.

PMID- 24033531
TI  - S-100 protein-positive mast cells in canine paranal sinus (Sinus paranalis).
AB  - The aim of this study was to establish the immunocytochemical expression of S-100
      protein in mast cells, localized in the wall of dog's paranal sinus. Control
      serial sections were used for immunocytochemical detection of tryptase-positive
      mast cells. It was observed that S-100-positive cells have the same morphology
      and localization as the tryptase-positive mast cells, which indicated that S-100
      positive cells are most probably mast cells with abilities as dendritic cells. In
      conclusion, for the first time, the current study gave evidence that mast cells
      in this organ possess one more function, such as dendritic cells. 

PMID- 24033533
TI  - Protective immunity by oral immunization with heat-killed Shigella strains in a
      guinea pig colitis model.
AB  - The protective efficacy of and immune response to heat-killed cells of monovalent
      and hexavalent mixtures of six serogroups/serotypes of Shigella strains (Shigella
      dysenteriae 1, Shigella flexneri 2a, S. flexneri 3a, S. flexneri 6, Shigella
      boydii 4, and Shigella sonnei) were examined in a guinea pig colitis model. A
      monovalent or hexavalent mixture containing 1 * 10(7) of each serogroup/serotype
      of heat-killed Shigella cells was administered orally on Days 0, 7, 14 and 21. On
      Day 28, the immunized animals were challenged rectally with 1 * 10(9) live
      virulent cells of each of the six Shigella serogroups/serotypes. In all immunized
      groups, significant levels of protection were observed after these challenges.
      The serum titers of IgG and IgA against the lipopolysaccharide of each of the six
      Shigella serogroups/serotypes increased exponential during the course of
      immunization. High IgA titers against the lipopolysaccharide of each of the six
      Shigella serogroups/serotypes were also observed in intestinal lavage fluid from
      all immunized animals. These data indicate that a hexavalent mixture of heat
      killed cells of the six Shigella serogroups/serotypes studied would be a possible
      broad-spectrum candidate vaccine against shigellosis. 

PMID- 24033532
TI  - Pathogenesis and outcomes of traumatic injuries of the esophagus.
AB  - Traumatic injury of the esophagus is extremely uncommon. The aims of this study
      were to use the Pennsylvania Trauma Outcome Study (PTOS) database to identify
      clinical factors predictive of esophageal trauma, and to report the morbidity and
      mortality of this injury. A cross-sectional review of patients presenting to 20
      Level I trauma centers in Pennsylvania from 2004 to 2010 was performed. We
      compared clinical and demographic variables between patients with and without
      esophageal trauma both prior to and after arrival in the emergency room (ER).
      Primary mechanism of injury and clinical outcomes were analyzed. There were 231
      694 patients and 327 (0.14%) had esophageal trauma. Patients with esophageal
      trauma were considerably younger than those without this injury. The risk of
      esophageal trauma was markedly increased in males (odds ratio [OR] = 2.62 [CI
      1.98-3.47]). The risk was also increased in African Americans (OR = 4.61 [CI 3.65
      5.82]). Most cases were from penetrating gunshot and stab wounds. Only 34 (10.4%)
      of esophageal trauma patients underwent an upper endoscopy; diagnosis was usually
      made by CT, surgery, or autopsy. Esophageal trauma patients were more likely to
      require surgery (35.8% vs. 12.5%; P < 0.001). Patients with esophageal trauma had
      a substantially higher mortality than those without the injury (20.5% vs. 1.4%; P
      < 0.005). In logistic regression modeling, traumatic injury of the esophagus (OR
      = 3.43 [2.50-4.71]) and male gender (OR = 1.52 [1.46-1.59]) were independently
      associated with mortality. For those patients with esophageal trauma, there was
      an association between trauma severity and mortality (OR = 1.10 [1.07-1.12]) but
      not for undergoing surgery within the first 24 hours of hospitalization (OR =
      0.84; 0.39-1.83). Our study on traumatic injury of the esophagus is in
      concordance with previous studies demonstrating that this injury is rare but
      carries considerable morbidity (~46%) and mortality (~20%). The injury has a
      higher morbidity and mortality when the thoracic esophagus is involved compared
      to the cervical esophagus alone. The injury most commonly occurs in younger,
      Black males suffering gunshot wounds. Efforts to control gun violence in
      Pennsylvania are of paramount importance. 

PMID- 24033534
TI  - Recognition of similar objects using simulated prosthetic vision.
AB  - Due to the limitations of existing techniques, even the most advanced visual
      prostheses, using several hundred electrodes to transmit signals to the visual
      pathway, restrict sensory function and visual information. To identify the
      bottlenecks and guide prosthesis designing, psychophysics simulations of a visual
      prosthesis in normally sighted individuals are desirable. In this study,
      psychophysical experiments of discriminating objects with similar profiles were
      used to test the effects of phosphene array parameters (spatial resolution, gray
      scale, distortion, and dropout rate) on visual information using simulated
      prosthetic vision. The results showed that the increase in spatial resolution and
      number of gray levels and the decrease in phosphene distortion and dropout rate
      improved recognition performance, and the accuracy is 78.5% under the optimum
      condition (resolution: 32 * 32, gray level: 8, distortion: k = 0, dropout: 0%).
      In combined parameter tests, significant facial recognition accuracy was achieved
      for all the images with k = 0.1 distortion and 10% dropout. Compared with other
      experiments, we find that different objects do not show specific sensitivity to
      the changes of parameters and visual information is not nearly enough even under
      the optimum condition. The results suggests that higher spatial resolution and
      more gray levels are required for visual prosthetic devices and further research
      on image processing strategies to improve prosthetic vision is necessary,
      especially when the wearers have to accomplish more than simple visual tasks. 

PMID- 24033535
TI  - Offsets and conservation of the species of the EU habitats and birds directives.
AB  - Biodiversity offsets are intended to achieve no net loss of biodiversity due to
      economic and human development. A variety of biodiversity components are
      addressed by offset policies. It is required that loss of protected species due
      to development be offset under the EU Habitats and Birds Directives in Europe. We
      call this type of offset a species-equality offset because the offset pertains to
      the same species affected by the development project. Whether species equality
      can be achieved by offset design is unknown. We addressed this gap by reviewing
      derogation files (i.e., specific files that describe mitigation measures to
      ensure no net loss under the EU Habitats and Birds Directives) from 85
      development projects in France (2009-2010). We collected information on type of
      effect (reversible vs. irreversible) and characteristics of affected and offset
      sites (i.e., types of species, total area). We analyzed how the type of effect
      and the affected-site characteristics influenced the occurrence of offset
      measures. The proportion of species targeted by offset measures (i.e., offset
      species) increased with the irreversibility of the effect of development and the
      conservation status of the species affected by development (i.e., affected
      species). Not all effects on endangered species (International Union for
      Conservation of Nature Red List) were offset; on average, 82% of affected species
      would be offset. Twenty-six percent of species of least concern were offset
      species. Thirty-five percent of development projects considered all affected
      species in their offset measures. Species richness was much lower in offset sites
      than in developed sites even after offset proposals. For developed areas where
      species richness was relatively high before development, species richness at
      offset sites was 5-10 times lower. The species-equality principle appears to have
      been applied only partially in offset policies, as in the EU directives. We
      suggest the application of this principle through offsets is highly important for
      the long-term conservation of biodiversity in Europe. Compensaciones y
      Conservacion de las Especies de las Directivas de Habitats y Aves de la UE. 

PMID- 24033536
TI  - Combined gamma-tocotrienol and Met inhibitor treatment suppresses mammary cancer
      cell proliferation, epithelial-to-mesenchymal transition and migration.
AB  - OBJECTIVES: Dysregulation of Met signalling is associated with malignant
      transformation. Combined treatment has been shown to reduce Met activation and
      mammary tumour cell proliferation. Experiments here, were conducted to determine
      mechanisms involved in mediating anti-cancer effects of combined gamma
      tocotrienol and SU11274 (Met inhibitor) treatment in various mammary cancer cell
      lines. MATERIALS AND METHODS: Treatment effects on mouse (+SA) and human (MCF-7,
      and MDA-MB-231) mammary cancer cell lines, and normal mouse (CL-S1) and human
      (MCF10A) mammary epithelial cell lines were compared. Cell proliferation and
      survival were determined by MTT assay and Ki-67 staining; protein expression was
      determined by western blot analysis. Immunofluorescence staining was also used to
      characterize expression and localization of multiple epithelial and mesenchymal
      markers. Cell migration was determined using a wound-healing assay. RESULTS:
      Combined treatment with gamma-tocotrienol and SU11274 resulted in synergistic
      inhibition of +SA, MCF-7, and MDA-MB-231, but not CL-S1 or MCF10A cell growth
      that was associated with reduction in Akt STAT1/5 and NFkappaB activation and
      corresponding blockade in epithelial-to-mesenchymal transition, as indicated by
      increased expression of E-cadherin, beta-catenin, and cytokeratins 8/18
      (epithelial markers) and corresponding reduction in vimentin (mesenchymal marker)
      and reduction in cancer cell motility. CONCLUSIONS: Suggest that combined gamma
      tocotrienol and Met inhibitor treatment may provide benefit in treatment of
      breast cancers characterized by aberrant Met activity.

PMID- 24033537
TI  - Clinical characteristics of Graves' orbitopathy in patients showing discrepancy
      between levels from TBII assays and TSI bioassay.
AB  - OBJECTIVE: To investigate clinical characteristics of patients with Graves'
      orbitopathy (GO) who showed discrepancies between levels of thyroid-stimulating
      immunoglobulin (TSI) and thyrotropin-binding inhibitory immunoglobulin (TBII).
      DESIGN: Comparative case series. PATIENTS: A total of 317 patients with GO in
      whom Mc4-TSI and M22-TRAb (third-generation TBII) were measured simultaneously.
      Patients were divided into four groups according to TRAb levels as followings:
      Group 1, TBII and TSI < median value; Group 2, TBII >= median, TSI < median;
      Group 3, TBII < median, TSI >= median; Group 4, both TBII and TSI >= median.
      MEASUREMENT: Endocrine and ophthalmic clinical manifestations in each group.
      RESULTS: The median value of M22-TRAb was 6.11 IU/l and that of Mc4-TSI was 415.1
      (SRR%). One hundred seventeen patients were classified as Group 1, 41 patients as
      Group 2, 41 patients as group 3 and 118 patients as group 4. Mean CAS was
      significantly higher in Groups 3 (2.2) and 4 (2.2) than in Groups 1 (1.6) and 2
      (1.4; P = 0.001, ANOVA). Mean modified NOSPECS scores were significantly higher
      (P < 0.001, ANOVA) in Groups 3 (4.1) and 4 (4.1) than in Groups 1 (3.1) and 2
      (2.3). The proportion of patients with hyperthyroidism was larger in Group 2
      (85.4% [35/41 patients]) than in Group 3 (48.8% [20/41 patients]; P = 0.002).
      CONCLUSIONS: GO is more active and severe in patients with predominant Mc4-TSI
      than in patients with predominant M22-TRAb. Patients with hyperthyroidism were
      more likely to be included with patients with predominant M22-TRAb than with
      predominant Mc4-TSI.

PMID- 24033538
TI  - Multidrug-resistant TB in Zambia: review of national data from 2000 to 2011.
AB  - BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is posing a great threat to
      global TB control. The burden in Zambia is not well defined because routine
      surveillance data are scarce. We reviewed national MDR-TB data for the last
      decade to inform future public health policy with respect to MDR-TB in Zambia.
      METHOD: Retrospective review of national surveillance of MDR-TB data, TB
      programme and laboratory reports between 2000 and 2011. RESULTS: The total number
      of DSTs performed during this 11-year period was 2,038 and accounted for 2.6%
      (2,038/78,639) of all the retreatment cases notified. The total number of
      diagnosed MDR-TB cases for this period was 446, of which 56.3% (251/446) were
      male and 41.7% (186/446) female. Only one child was found to have MDR-TB. Poly
      drug resistance accounted for 18.9% (172/911) of the DR-TB cases and 8.4% of the
      total DSTs. 8.8% (80/911) of the DR-TB cases showed either rifampicin mono- or
      poly-resistance other than MDR-TB. No XDR-TB was reported. There were no data
      available on DR-TB and HIV co-infection. Only 65 MDR-TB patients were notified
      and put on second-line treatment according to WHO guidelines. CONCLUSIONS:
      Multidrug-resistant tuberculosis may be an emerging challenge in Zambia. There is
      a need to invest in improving the capacity of the TB programme to detect and
      manage MDR-TB.

PMID- 24033539
TI  - Establishing epigenetic domains via chromatin-bound histone modifiers.
AB  - The eukaryotic nucleus harbors the DNA genome, which associates with histones and
      other chromosomal proteins into a complex referred to as chromatin. It provides
      an additional layer of so-called epigenetic information via histone modifications
      and DNA methylation on top of the DNA sequence that determines the cell's active
      gene expression program. The nucleus is devoid of internal organelles separated
      by membranes. Thus, free diffusive transport of proteins and RNA can occur
      throughout the space accessible for a given macromolecule. At the same time,
      chromatin is partitioned into different specialized structures such as nucleoli,
      chromosome territories, and heterochromatin domains that serve distinct
      functions. Here, we address the question of how the activity of chromatin
      modifying enzymes is confined to chromatin subcompartments. We discuss mechanisms
      for establishing activity gradients of diffusive chromatin-modifying enzymes that
      could give rise to distinct chromatin domains within the cell nucleus.
      Interestingly, such gradients might directly result from immobilization of the
      enzymes on the flexible chromatin chain. Thus, locus-specific tethering of these
      enzymes to chromatin could have the potential to establish, maintain, or modulate
      epigenetic patterns of characteristic domain size. 

PMID- 24033540
TI  - Nucleoside analog inhibits microRNA-214 through targeting heat-shock factor 1 in
      human epithelial ovarian cancer.
AB  - The important functions of heat shock factor 1 (HSF1) in certain malignant
      cancers have granted it to be an appealing target for developing novel strategy
      for cancer therapy. Here, we report that higher HSF1 expression is associated
      with more aggressive malignization in epithelial ovarian tumors, indicating that
      targeting HSF1 is also a promising strategy against ovarian cancer. We found that
      a nucleoside analog (Ly101-4B) elicits efficient inhibition on HSF1 expression
      and potent anticancer activity on epithelial ovarian cancer both in vitro and in
      vivo. Moreover, by targeting HSF1, Ly101-4B inhibits the biogenesis of microRNA
      214, which has been revealed to be overexpressed and to promote cell survival in
      human ovarian epithelial tumors. These findings demonstrate that Ly101-4B is a
      promising candidate for ovarian cancer therapy, and expand our understanding of
      HSF1, by revealing that it can regulate microRNA biogenesis in addition to its
      canonical function of regulating protein-coding RNAs.

PMID- 24033541
TI  - Effect of a prebiotic on performance of partridge.
AB  - An experiment was conducted to investigate the effect of a prebiotic on
      performance of partridge. The experiment was carried out with a total of eighty
      day-old male Chukar partridge (Alectoris chukar chukar) chicks in a completely
      randomized design. The dietary treatments consisted of a control and an
      experimental treatment, and each treatment was replicated four times with 10
      chicks per replicate. The experimental period lasted 16 weeks with a starter
      period (0-8 weeks) and a grower period (9-16 weeks). The control group was fed
      the basal diet, while the experimental group was fed the basal diet supplemented
      with 0.18% prebiotic Aspergillus meal in each period. Performance parameters
      included body weight gain, cumulative feed consumption and cumulative FCR and
      were recorded at biweekly intervals. Carcass characteristics and blood parameters
      were measured at the end of the experiment (week 16). Although the results showed
      that prebiotic had no significant effect on body weight gain and cumulative feed
      conversion ratio; however, the supplementation of Aspergillus meal significantly
      (p < 0.05) decreased cumulative feed consumption. Also prebiotic significantly
      increased percentages of breast and gastrointestinal tract, decreased percentage
      of back-neck, decreased blood triglyceride and total cholesterol content and
      increased blood calcium content. From this study, it was concluded that dietary
      supplementation of 0.18% Aspergillus meal might offer beneficial effects on
      partridge feed consumption, carcass quality and blood cholesterol.

PMID- 24033542
TI  - Regulation of fetal lung development in response to maternal overnutrition.
AB  - With the worldwide obesity epidemic, the proportion of women entering pregnancy
      overweight or obese has increased significantly in recent years. Babies born to
      obese women are at an increased risk of respiratory complications at birth and in
      childhood. In addition to maternal diabetes, there are a number of metabolic
      changes that the fetus of an overnourished mother experiences in utero that may
      modulate lung development and represent the mechanisms underlying the increased
      risk of respiratory complications. Herein we highlight a series of factors
      associated with the intrauterine environment of an overnourished mother that may
      impact on fetal lung development and lead to an increased risk of complications
      at birth or in postnatal life.

PMID- 24033543
TI  - Genetic analysis reveals diverse kin-directed routes to helping in the rifleman
      Acanthisitta chloris.
AB  - The social organization of cooperatively breeding species is extremely variable,
      with diverse social group composition and patterns of relatedness. Species that
      exhibit alternative routes to helping within the same population are potentially
      useful systems to investigate the causes and fitness consequences of diverse
      evolutionary pathways to cooperative behaviour. In this study, we use
      microsatellite markers and field observations to describe helping behaviour and
      patterns of relatedness in the unusual cooperative breeding system of the
      rifleman Acanthisitta chloris. First, we show that rifleman helpers consist of a
      remarkably diverse demographic, including males and females, who may be adult or
      juvenile, failed breeders or nonbreeders, or even successful breeders that
      simultaneously feed their own brood. Adult helpers mostly helped at first-brood
      nests, while first-brood juveniles assisted their parents at second broods.
      Second, we show that rifleman pairs are strictly sexually monogamous, and helpers
      did not gain any current reproductive success through helping. Third, genotyping
      showed that contrary to previous assumptions, helpers were closely related to the
      recipients of their care and preferentially directed care towards relatives over
      contemporaneous nests of nonrelatives. Finally, we show that variation in helper
      provisioning effort was attributed to age: juvenile helpers provisioned less than
      adults and were less responsive to the demands of a growing brood. Overall, our
      results show that the diverse routes to helping in this unusual species are
      driven by the common theme of kinship between helper and recipients, resulting in
      a previously underestimated potential for helpers to gain indirect fitness
      benefits. 

PMID- 24033544
TI  - A study of the endodontic workforce in Australia in 2010.
AB  - AIMS: To investigate the current workforce situation for specialist Endodontists
      in Australia to help plan for the future of the specialty. METHODOLOGY: An online
      questionnaire was sent via email to all registered Endodontists that were
      identified from the Australian and New Zealand Academy of Endodontists database
      and the Australian Dental Association Directory. The questionnaire comprised
      questions on demographic characteristics, practice type, teaching and research
      activities, busyness and expected retirement time. All results were transferred
      to a statistical software program (SPSS v.19) for analysis. RESULTS: The response
      rate was 50%. The majority of respondents (84%) were male. The most common
      (64.5%) type of practice was single location private practice. The majority (93%)
      of Endodontists are located in state capital cities. Many respondents (61%) did
      some teaching. A minority of respondents (16%) were currently involved in
      research. The next available nonemergency appointment was more than 1 week away
      for 84% of respondents. More than half the respondents (52%) do not have
      allocated time for emergency patients. Only 18% of respondents plan to retire in
      the next 5 years and another 15% within 5-10 years. Although 58% of practice
      owners indicated that they have sufficient space and facilities to employ another
      Endodontist, only 33% would consider to employ or have an associate join their
      practice. CONCLUSION: Most Endodontists in Australia are male private
      practitioners who work in a single state capital city location. Many teach but
      few carry out research. They are fully booked with routine patients and have no
      spare scheduled appointments for emergencies; these have to be seen at the end of
      the day, or between scheduled patients. There will be a steady rate of retirement
      in the future and only just enough newly qualified Endodontists are being trained
      to maintain the specialty workforce at current levels.

PMID- 24033545
TI  - Assessment of permanent brachytherapy combined with androgen deprivation therapy
      in an intermediate-risk prostate cancer group without a Gleason score of 4 + 3: a
      single Japanese institutional experience.
AB  - OBJECTIVES: To evaluate the outcome of low-dose-rate permanent brachytherapy
      combined with anti-androgen deprivation therapy for intermediate-risk prostate
      cancer excluding biopsy Gleason score 4 + 3. METHODS: Patients included in the
      intermediate-risk group were those presenting clinical stage T1c to T2c (by
      magnetic resonance imaging staging), Gleason score 3 + 4 or lower and/or prostate
      specific antigen less than 20 ng/mL, whereas those with clinical stage T1c to
      T2a, Gleason score 3 + 3 and prostate-specific antigen less than 10 ng/mL
      represented the low-risk group, and were used as controls. In the intermediate
      risk group, therapy with a luteinizing hormone-releasing hormone analog was
      continued for at least 6 months before and after permanent brachytherapy.
      RESULTS: A total of 147 low-risk group patients and 139 intermediate-risk group
      patients were included in the study. The median follow up was 51 and 52 months
      for the intermediate-risk group and low-risk group, respectively. The 5-year
      overall, cause-specific and distant-metastasis-free survival rates in the low
      risk group and intermediate-risk group were 97.6/99.2, 100/100 and 100/100%,
      respectively. The 5-year biochemical disease-free survival in these groups were
      95.9 and 92.5%, respectively (P = 0.18). There was no sexual activity and desire
      for erection before treatment in 50%, and in 46% of the patients in the low-risk
      group and intermediate-risk group, respectively. Overall satisfaction score at 2
      years after permanent brachytherapy significantly improved, compared with
      pretreatment (P = 0.0399). CONCLUSIONS: In intermediate-risk prostate cancer,
      excluding biopsy Gleason score 4 + 3, permanent brachytherapy combined with
      androgen deprivation therapy for 6 months or more represents an effective
      treatment option in Japanese patients, based on a favorable prognosis, adverse
      event profile and quality of life analysis.

PMID- 24033546
TI  - Comparison of reproductive outcome, including the pattern of loss, between
      couples with chromosomal abnormalities and those with unexplained repeated
      miscarriages.
AB  - AIM: Chromosomal abnormalities are an important cause of repeated miscarriage.
      Several studies have discussed the association between chromosomal abnormalities
      and repeated miscarriage. This study attempts to describe the pattern of
      miscarriage in this group of women and the eventual pregnancy outcome of couples
      with chromosomal abnormalities compared with couples with unexplained repeated
      pregnancy loss. MATERIAL AND METHODS: This was a retrospective study involving
      795 couples with repeated miscarriages. RESULTS: Out of 795 couples, 28 (3.52%)
      were found to have a chromosomal abnormality (carrier group). Over half (65.5%)
      of the chromosomal abnormalities were balanced reciprocal translocations. After
      referral, this carrier group had a total of 159 pregnancies, leading to 36 live
      births (22.6%) among 18 couples. The after referral miscarriage rate in the
      chromosomal anomaly group (55.6%) was significantly (P < 0.01) higher than that
      in the unexplained recurrent miscarriage group (28.1%). In couples with
      chromosomal anomaly, the miscarriages were more likely to occur between 6 and 12
      weeks' gestation. CONCLUSIONS: The encouraging cumulative live birth rate of
      64.3% for couples with chromosomal anomaly and repeated miscarriage suggests that
      further attempts at natural conception are a viable option.

PMID- 24033547
TI  - Completing the audit cycle: the impact of an electronic reporting system on the
      feedback loop in surgical specialties.
AB  - INTRODUCTION: The feedback loop of incident reporting is essential in improving
      patient care. Few studies have followed the loop around its cycle and little data
      are available concerning the impact of interventions. We investigated the
      feedback loop before and after the implementation of an electronic reporting
      system. METHOD: Data were collected before and after our intervention. Data were
      analyzed in terms of the percentage of incidents evaluated, the percentage of
      incidents resulting in action, whether correlations demonstrated an increased
      rate of action taken as incident risk score increased. RESULTS: Prior to our
      intervention, 43% and 40% of incidents reported were evaluated and acted upon,
      respectively. Postintervention, the number of incidents reported increased by
      198%. All incidents were evaluated and 66% were acted upon. Both pre- and
      postintervention, no correlations demonstrated an increase in action taken as
      incident severity increased. CONCLUSION: Our intervention resulted in a
      considerable increase in the number of incidents reported, evaluated, and acted
      upon. Such an effect would be expected to improve patient safety, although
      further studies are needed to definitively confirm this. We therefore recommend
      the use of electronic systems and further studies to evaluate their impact on
      patient safety.

PMID- 24033548
TI  - Mitochondrial translation factors of Trypanosoma brucei: elongation factor-Tu has
      a unique subdomain that is essential for its function.
AB  - Mitochondrial translation in the parasitic protozoan Trypanosoma brucei relies on
      imported eukaryotic-type tRNAs as well as on bacterial-type ribosomes that have
      the shortest known rRNAs. Here we have identified the mitochondrial translation
      elongation factors EF-Tu, EF-Ts, EF-G1 and release factor RF1 of trypanosomatids
      and show that their ablation impairs growth and oxidative phosphorylation. In
      vivo labelling experiments and a SILAC-based analysis of the global proteomic
      changes induced by EF-Tu RNAi directly link EF-Tu to mitochondrial translation.
      Moreover, EF-Tu RNAi reveals downregulation of many nuclear encoded subunits of
      cytochrome oxidase as well as of components of the bc1-complex, whereas most
      cytosolic ribosomal proteins were upregulated. Interestingly, T. brucei EF-Tu has
      a 30-amino-acid-long, highly charged subdomain, which is unique to
      trypanosomatids. A combination of RNAi and complementation experiments shows that
      this subdomain is essential for EF-Tu function, but that it can be replaced by a
      similar sequence found in eukaryotic EF-1a, the cytosolic counterpart of EF-Tu. A
      recent cryo-electron microscopy study revealed that trypanosomatid mitochondrial
      ribosomes have a unique intersubunit space that likely harbours the EF-Tu binding
      site. These findings suggest that the trypanosomatid-specific EF-Tu subdomain
      serves as an adaption for binding to these unusual mitochondrial ribosomes. 

PMID- 24033549
TI  - Delay in surgical treatment of patients with hilar cholangiocarcinoma: does time
      impact outcomes?
AB  - BACKGROUND: Substantial time elapses before patients with hilar
      cholangiocarcinoma (HCC) receive surgical treatment because of time-consuming
      preoperative staging and other interventions, including biliary drainage and
      portal vein embolization. Prolonged times potentially lead to unresectability and
      the formation of metastases, yet these issues have not been investigated
      previously in HCC. This study aimed to evaluate the time between onset of
      symptoms and the provision of ultimate treatment in patients with HCC and the
      impact of the length of time on outcomes. METHODS: Delays in the treatment of
      consecutive patients with HCC were evaluated by contacting general practitioners
      (GPs) and extracting data from hospital files. Time periods were correlated with
      resectability, occurrence of metastasis, tumour stage and survival using logistic
      and Cox regression analyses. RESULTS: Treatment times in 209 consecutive HCC
      patients were evaluated. The median time from first GP visit until presentation
      at the tertiary centre was 35 days. Time until treatment was longer when initial
      symptoms did not include jaundice (non-specific symptoms, P < 0.001). Duration of
      workup and preoperative biliary drainage at the tertiary centre prior to final
      surgical treatment resulted in an additional median time of 74 days. No
      correlation was found between treatment time in weeks and resectability [odds
      ratio (OR) 1.010, 95% confidence interval (CI) 0.985-1.036], metastasis (OR =
      0.947, 95% CI 0.897-1.000), tumour stage (OR = 1.006, 95% CI 0.981-1.031) or
      survival in resected patients (hazard ratio = 0.996, 95% CI 0.975-1.018).
      CONCLUSIONS: The time that elapses between the presentation of symptoms and final
      treatment in patients with HCC is substantial, especially in patients with non
      specific symptoms. This time, however, does not affect resectability, metastasis,
      tumour stage or survival, which suggests that preoperative optimization should
      not be omitted because of potential delays in treatment.

PMID- 24033551
TI  - The fate of indefinite and low-grade dysplasia in ulcerative colitis and primary
      sclerosing cholangitis colitis before and after liver transplantation.
AB  - BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and ulcerative
      colitis (UC) are at an increased risk of colorectal neoplasia, but it is unknown
      if liver transplantation (LT) alters neoplasia progression. AIM: To examine the
      natural history of indefinite dysplasia (IND) and low-grade dysplasia (LGD) that
      develop in patients with PSC-UC with and without LT. METHODS: We performed a
      retrospective review of patients with PSC and UC evaluated at our institution
      between 1993 and 2011 who were diagnosed with IND or LGD before or after LT for
      PSC. The primary end point was neoplasia progression or persistent LGD. RESULTS:
      Ninety-six patients (non-LT n = 63, LT n = 33) were examined. For the IND group,
      multifocal lesions were significantly associated with time to neoplasia
      progression [hazard ratio (HR), 3.5; 95% confidence interval (CI), 1.3-9.7],
      while 5-aminosalicylate (5-ASA) use was protective (HR, 0.2; 95% CI, 0.1-0.6).
      For patients with LGD, multifocal lesions were significantly associated with the
      primary end point (HR, 7.1; 95% CI, 1.7-28.3), while LT was protective (HR, 0.3;
      95% CI, 0.1-0.9). CONCLUSIONS: In PSC-UC patients with IND, 5-ASA use was
      associated with a decreased the risk of neoplasia progression, regardless of
      transplant status. In contrast, multifocal IND and LGD were associated with
      neoplasia progression or persistent LGD. Patients who developed LGD following LT
      for PSC were less likely to have progressive neoplasia or persistent LGD,
      compared with those who had not been transplanted.

PMID- 24033550
TI  - Psychiatric comorbidity and 12-step participation: a longitudinal investigation
      of treated young adults.
AB  - BACKGROUND: Evidence indicates that 12-step mutual-help organizations (MHOs),
      such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA), can play an
      important role in extending and potentiating the recovery benefits of
      professionally delivered addiction treatment among young adults with substance
      use disorders (SUD). However, concerns have lingered regarding the suitability of
      12-step organizations for certain clinical subgroups, such as those with dual
      diagnosis (DD). This study examined the influence of diagnostic status (DD vs.
      SUD-only) on both attendance and active involvement (e.g., having a sponsor,
      verbal participation during meetings) in, and derived benefits from, 12-step MHOs
      following residential treatment. METHODS: Young adults (N = 296; 18 to 24 years
      old; 26% female; 95% Caucasian; 47% DD [based on structured diagnostic
      interview]), enrolled in a prospective naturalistic study of SUD treatment
      effectiveness, were assessed at intake and 3, 6, and 12 months posttreatment on
      12-step attendance/active involvement and percent days abstinent (PDA). t-Tests
      and lagged, hierarchical linear models (HLM) examined the extent to which
      diagnostic status influenced 12-step participation and any derived benefits,
      respectively. RESULTS: For DD and SUD-only patients, posttreatment attendance and
      active involvement in 12-step organizations were similarly high. Overall, DD
      patients had significantly lower PDA relative to SUD-only patients. All patients
      appeared to benefit significantly from attendance and active involvement on a
      combined 8-item index. Regarding the primary effects of interest, significant
      differences did not emerge in derived benefit between DD and SUD-only patients
      for either attendance (p = 0.436) or active involvement (p = 0.062). Subsidiary
      analyses showed, however, that DD patients experienced significantly greater
      abstinence-related benefit from having a 12-step sponsor. CONCLUSIONS: Despite
      concerns regarding the clinical utility of 12-step MHOs for DD patients, findings
      indicate that DD young adults participate and benefit as much as SUD-only
      patients, and may benefit more from high levels of active involvement,
      particularly having a 12-step sponsor. Future work is needed to clarify how
      active 12-step involvement might offset the additional recovery burden of a
      comorbid mental illness on substance use outcomes.

PMID- 24033553
TI  - How much immunosuppression is needed after liver transplantation?

PMID- 24033552
TI  - Differentiating suicide ideators from attempters: violence--a research note.
AB  - Which factors distinguish suicide attempters from suicide ideators is a
      relatively neglected question in suicidology. Data from the 2001 Youth Risk
      Behavior Survey, encompassing 1,439 youth suicide ideators and 1,097 attempters,
      was used to explore which factors best differentiate suicide attempters from
      ideators, with a focus on violence involvement. Measures of violence include the
      contexts of fights, dating, and weapons carrying. Controls were incorporated for
      psychiatric disorders, risky sexual behavior, school integration, and
      demographics. Controlling for the other variables, violence differentiated
      attempts from ideation: fighting (OR = 2.18) and weapon carrying (OR = 1.13).
      Psychiatric factors that predicted attempts over ideation included major
      depression (OR = 1.86), use of cocaine (OR = 2.34), and having a suicide plan (OR
      = 2.69), while demographic factors included gender, age, residence in the
      Midwest, and Hispanic, African American, or Asian ethnicity. A supplementary
      analysis (N = 11,546) determined that violence also helped to differentiate
      suicide ideators from nonsuicidal youth. Four factors (including violence
      involvement, eating disorders, and gender consistently) differentiated both
      between suicide attempts and ideation, and also between suicide ideators and
      nonsuicidal youth. The link between violence involvement and suicidality is
      interpreted in terms of the capability for suicide from the interpersonal theory
      of suicide. 

PMID- 24033554
TI  - The carrier prevalence of severe combined immunodeficiency, lavender foal
      syndrome and cerebellar abiotrophy in Arabian horses in South Africa.
AB  - REASONS FOR PERFORMING STUDY: The carrier prevalence of severe combined
      immunodeficiency (SCID), lavender foal syndrome (LFS) and cerebellar abiotrophy
      (CA) in Arabian foals in South Africa was determined in order to quantify the
      potential impact of these conditions locally. Furthermore, the carrier prevalence
      of SCID prior to and following the introduction of a genetic test was compared to
      evaluate the effect of testing in the population. OBJECTIVES: To estimate the
      carrier prevalence of SCID, LFS and CA in registered purebred Arabians born in
      South Africa in the 2004/5 and 2009/10 foaling seasons and compare the changes in
      prevalence in these disorders between the 2 groups of foals. STUDY DESIGN: Cross
      sectional survey. METHODS: Samples were collected from individuals randomly
      selected from 2 populations of purebred Arabian foals born during the 2004/5 and
      2009/10 foaling seasons. Genetic testing for SCID, LFS and CA was performed on
      DNA extracts using specific polymerase chain reactions, with the products being
      analysed using fragment analysis on a genetic analyser. RESULTS: The carrier
      prevalence of LFS and CA for the 2009/10 season was 11.7% (95% confidence
      interval [CI] 7.6-17.0%) and 5.1% (95% CI 2.5-9.1%), respectively, with no
      statistically significant change in prevalence between the 2004/5 and 2009/10
      foaling seasons. However, the carrier prevalence of SCID was found to have
      decreased significantly from 6.4% (95% CI 4.8-8.3%) in the 2004/5 foals to 3.4%
      (95% CI 2.2-5.1%) in the 2009/10 foals (P = 0.009). CONCLUSIONS: The results of
      this study indicate that genetic screening of Arabian horses for SCID may have
      played a role in significantly reducing the carrier prevalence within the
      breeding population and thereby reducing the birth of clinically affected
      individuals. This study provides an indication of the positive effect of genetic
      screening for specific conditions in horses.

PMID- 24033555
TI  - Unique properties of cluster of differentiation 93 in the umbilical cord blood of
      neonates.
AB  - It has previously been reported by these authors that cluster of differentiation
      (CD) 93 is co-expressed on naive T-lymphocytes (CD4(+) CD45RA(+) cells) in
      neonatal umbilical cord blood cells (UCBCs) but not on normal adult peripheral
      blood cells (PBCs). In this study, expression of CD93 on other lymphocyte subsets
      and the concentration of soluble formed CD93 (sCD93) in serum or culture
      supernatants from neonatal umbilical cord blood (UCB) was examined. It was found
      that CD93 is also co-expressed on CD2(+) , CD16(+) , CD56(+) or CD25(+) cells in
      the lymphocyte population of neonatal UCBCs, but not on normal adult PBCs. The
      concentrations of sCD93 in serum and culture supernatants from neonatal UCB were
      significantly greater than those from normal adult peripheral blood. The
      concentrations of sCD93 in culture supernatants from neonatal UCBCs and normal
      adult PBCs treated with phorbol 12-myristate 13-acetate (PMA) were significantly
      enhanced compared with those without PMA treatment. The degree of enhancement of
      sCD93 by PMA in culture supernatants from neonatal UCBCs was significantly
      greater than that of normal adult PBCs and enhancement of sCD93 by PMA in the
      culture supernatants from neonatal UCBCs and normal adult PBCs was significantly
      suppressed by PKC inhibitor. Interestingly, the high concentration of serum sCD93
      in neonates was significantly decreased in sera from infants at 1 month after
      birth. Expression of CD93 on the lymphocyte population of PBCs from infants at 1
      month after birth was also significantly decreased, compared with that for
      neonatal UCBCs. These findings indicate that CD93 in neonatal UCB has unique
      properties as an immunological biomarker. 

PMID- 24033556
TI  - It's a funny thing....

PMID- 24033557
TI  - The use of a double-lumen central venous catheter for airway management in
      pediatric patients undergoing laryngeal papillomatosis surgery.
AB  - PURPOSE: To evaluate the efficacy and safety of a spontaneous ventilation
      anesthesia technique with insufflation of oxygen and volatile agent through a
      double-lumen central venous catheter (DLCVC) in pediatric patients undergoing
      suspension laryngoscopic surgery for laryngeal papillomatosis. METHODS: Thirty
      six pediatric patients with laryngeal papillomatosis undergoing suspension
      laryngoscopic surgery were anesthetized with oxygen and volatile anesthetic
      insufflation while spontaneously breathing. Anesthesia was induced by inhalation
      of 8% sevoflurane in oxygen by mask. Atropine, dexamethasone, lidocaine, and
      midazolam were administered intravenously. The tip of a 7Fr DLCVC was inserted
      below the glottis after placement of the laryngoscope and establishing
      suspension. Anesthesia was maintained with insufflation of 4-6% sevoflurane and
      oxygen with a total fresh gas flow of 6 l.min(-1) through the 14G (larger lumen)
      of the DLCVC. Endtidal carbon dioxide tension (PetCO2) was monitored using the
      other lumen of the DLCVC, which was connected to the CO2 sampling line. Duration
      of the procedure as well as total anesthesia time was recorded.
      Electrocardiography (ECG), heart rate (HR), mean arterial pressure (MAP), oxygen
      saturation (SpO2), and PetCO2 were also monitored. Arterial blood was sampled for
      blood gas analysis including pH, PaO2 , PaCO2 , and actual base excess (ABE).
      Complications, including intraoperative patient movement, hypoxemia (SpO2 < 95%
      during oxygen insufflation), nausea, vomiting, bronchospasm, and arrhythmias,
      were recorded. RESULTS: There was a significant increase in PetCO2 and PaCO2 (P
      values <0.05) as well as a decrease in ABE, pH, and PaO2 (P values <0.05) in
      samples collected before and after surgery. MAP, HR, and SpO2 after surgery were
      not significantly different from after induction values (P values >0.05). During
      surgery, SpO2 < 95% in three cases and body movements in three cases were
      observed. No patient had any other of the complications previously described.
      Furthermore, no postsurgical endotracheal intubation was needed in any patient.
      CONCLUSION: After establishing an adequate depth of anesthesia, a spontaneous
      ventilation anesthesia technique with insufflation of oxygen and volatile agent
      through a DLCVC is feasible in pediatric patients undergoing suspension
      laryngoscopic surgery for laryngeal papillomatosis.

PMID- 24033558
TI  - Primary and secondary immune responses to keyhole limpet hemocyanin in rats after
      infusion of hemoglobin vesicle, an artificial oxygen carrier.
AB  - Hemoglobin vesicles (HbVs), artificial oxygen carriers encapsulating concentrated
      Hb solution on phospholipid vesicles (liposomes), are promising candidates for
      clinically useful transfusion. Although HbV infusion transiently suppressed the
      proliferative response of rat splenic T-cells to concanavalin A or keyhole limpet
      hemocyanin (KLH), a T-cell-dependent antigen, in ex vivo culture conditions, HbV
      infusion did not affect the primary IgG antibody response. We extended our
      assessment of the effects of HbV infusion on the systemic immune response using
      primary and secondary responses to KLH in rats. We observed that the generation
      of primary anti-KLH IgM antibody in HbV-infused rats was not suppressed but was
      instead higher than those in saline-infused rats. Furthermore, HbV infusion did
      not suppress the increase of IgG subclass of KLH antibody in secondary response.
      The T cell response to KLH of bulk spleen cells, as derived from 2-3 months after
      secondary KLH immunization, was unaffected by infusion of HbV, suggesting that
      HbV loading has no suppressive effect on homeostatic survival of memory T-cells
      against KLH. These results indicate that HbV is highly biocompatible in systemic
      immune responses in rats. 

PMID- 24033559
TI  - Review of equine piroplasmosis.
AB  - Equine piroplasmosis is caused by one of 2 erythrocytic parasites Babesia caballi
      or Theileria equi. Although the genus of the latter remains controversial, the
      most recent designation, Theileria, is utilized in this review. Shared
      pathogenesis includes tick-borne transmission and erythrolysis leading to anemia
      as the primary clinical outcome. Although both parasites are able to persist
      indefinitely in their equid hosts, thus far, only B. caballi transmits across
      tick generations. Pathogenesis further diverges after transmission to equids in
      that B. caballi immediately infects erythrocytes, whereas T.equi infects
      peripheral blood mononuclear cells. The recent re-emergence of T.equi in the
      United States has increased awareness of these tick-borne pathogens, especially
      in terms of diagnosis and control. This review focuses in part on factors leading
      to the re-emergence of infection and disease of these globally important
      pathogens.

PMID- 24033560
TI  - Antitumor efficacy of C-X-C motif chemokine ligand 14 in hepatocellular carcinoma
      in vitro and in vivo.
AB  - C-X-C motif chemokine ligand 14 (CXCL14) is a novel gene that is expressed in
      many normal cells but is absent from or expressed at very low levels in cancerous
      tissues such as head and neck squamous cell carcinoma (HNSCC), prostate cancer,
      and pancreatic cancer. However, the relationship between CXCL14 and
      hepatocellular carcinoma (HCC) remains unclear. Therefore, the exact function of
      CXCL14, which may modulate antitumor immune responses in certain cancers, was
      evaluated. CXCL14 was downregulated in HCC tissues compared to adjacent normal
      tissues. Moreover, overexpression of CXCL14 had an inhibitory effect on cell
      proliferation, induced apoptosis and inhibited the invasion of HCC cells in
      vitro. Upregulation of CXCL14 by lentivirus also significantly suppressed the
      growth of subcutaneous tumors in nude mice in vivo. We further demonstrated that
      the loss of CXCL14 expression was regulated by promoter hypermethylation. CXCL14
      induced tumor cell apoptosis through both the mitochondrial and nuclear apoptosis
      pathways. CXCL14 suppressed tumor cell proliferation through regulation of the
      cell cycle by downregulation of cyclins and cyclin-dependent kinases. In
      conclusion, CXCL14 plays a pivotal role as a potential tumor suppressor in HCC.
      The re-expression or upregulation of this gene may provide a novel strategy in
      HCC therapy in the future. 

PMID- 24033561
TI  - Treated and untreated women with idiopathic precocious puberty: long-term follow
      up and reproductive outcome between the third and fifth decades.
AB  - CONTEXT: Central precocious puberty (CPP), treated or untreated, may have
      implications in adulthood. OBJECTIVE: To assess the reproductive outcome and
      social adjustment of former CPP women between the 3rd and 5th decades of life.
      DESIGN: Cross-sectional study of an historical cohort. METHODS: Demographic data
      and gynaecological history of 214 CPP women aged 25-56 years [135 GnRH analogue
      (GnRHa)-treated, 18 cyproterone acetate (CyA)-treated, 61 untreated] and of 446
      controls with normal puberty, matched for age and year of birth, were recorded in
      a structured interview. RESULTS: Marital status, education and number of children
      were similar in CPP women and controls. Clinical hyperandrogenism (acne/hirsutism
      with oligomenorrhoea) was more frequently reported in CPP women than in controls:
      GnRHa-treated 29.6% vs 17.4% (P = 0.006), CyA-treated 50% vs 20.4% (P = 0.04),
      untreated 34.4% vs 17.2% (P = 0.003), with no significant difference between CPP
      groups. Spontaneous pregnancy was similarly achieved by treated CPP and controls:
      GnRHa-treated 90.4% vs 93.4%, CyA-treated 86.7% vs 90.2%. Assisted fertilization
      rate was higher in untreated CPP than treated CPP groups (P = 0.006) and controls
      (P = 0.03). Untreated CPP was the only parameter associated with clinical
      hyperandrogenism (OR=2.04, 95% CI, 1.0-4.16, P = 0.07) and fertility problems
      (OR=3.40, 95% CI, 1.15-10.0, P = 0.047). Course of pregnancy was uneventful in
      90.2% of CPP women and 90.9% of controls. CONCLUSIONS: The increased rate of
      clinical hyperandrogenism among CPP women implies that the underlying
      neuroendocrine dysfunction persists into adult life. Pubertal suppression
      treatment may have a protective effect as fertility problems were more prevalent
      only among untreated CPP women. Educational achievements and marital status were
      unaffected by CPP.

PMID- 24033562
TI  - Characterization of plasma cytokines in an infant population cohort of challenge
      proven food allergy.
AB  - BACKGROUND: Sensitization to food allergens indicates the production of food
      specific IgE; however, sensitization is not a definite indicator of allergic
      reaction upon ingestion (N Engl J Med, 344, 2001, 30: J Allergy Clin Immunol,
      120, 2007, 491). Currently, food challenge is the best approach to identify the
      presence or absence of allergy. While 95% positive predictive values (PPVs)
      thresholds for sIgE can assist with identifying increased likelihood of allergy
      among those who are sensitized, there are no specific biological markers that
      differentiate between allergic and sensitized individuals. OBJECTIVES: To
      determine whether plasma serum cytokine profiles predict (i) sensitization to
      peanut and egg and (ii) food allergy among sensitized infants. METHODS: Peanut
      sensitized (PT) and egg-sensitized 14-month-old infants and nonsensitized
      controls enrolled in HealthNuts, a population-based study of food allergy,
      underwent an oral food challenge (OFC). Blood was collected within 1 h after OFC.
      Serum levels of Th1, Th2 and regulatory cytokines were determined in allergic (n
      = 79), sensitized (n = 40) and nonsensitized, nonallergic (n = 37) infants by
      multiplex assay. RESULTS: Food-sensitized infants had significantly higher plasma
      IL-4, IL-13, IL-12p70 and lower IL-10 levels compared to nonsensitized infants.
      IL-10 and IL-6 levels were significantly higher in sensitized compared with
      allergic infants. Egg-allergic infants had significantly higher IL-13 and IL
      12p70 levels compared to peanut-allergic (PA) infants. CONCLUSION: Levels of Th2
      related cytokines in plasma are higher in food-sensitized infants, irrespective
      of clinical food allergy status. In contrast, IL-10 levels appear to predict food
      allergy among sensitized infants. Differences in IL-13 and IL-12p70 between egg-
      and peanut-allergic infants could help explain the different resolution rates of
      the allergies.

PMID- 24033563
TI  - Effects of Rho-kinase inhibition on myosin light chain phosphorylation and
      obstruction-induced detrusor overactivity.
AB  - OBJECTIVES: To study the relationship between myosin light chain phosphorylation
      of the detrusor muscle and spontaneous smooth muscle contractions in a rabbit
      model of partial outlet obstruction. METHODS: New Zealand white rabbit urinary
      bladders were partially obstructed for 2 weeks. Rabbits were euthanized, detrusor
      muscle strips were hung on a force transducer and spontaneous activity was
      measured at varying concentrations (0-0.03 MUM/L) of the Rho-kinase inhibitors
      GSK 576371 or 0.01 MUM/L Y27632. Basal myosin light chain phosphorylation was
      measured by 2-D gel electrophoresis in control and GSK 576371-treated strips.
      RESULTS: Both drugs suppressed the force of spontaneous contractions, whereas GSK
      576371 had a more profound effect on the frequency of the contractions. The IC50
      values for the inhibition of frequency and force of spontaneous contractions were
      0.17 MUM/L and 0.023 MUM/L for GSK 576371, respectively. The compound
      significantly decreased the basal myosin light chain phosphorylation from 28.0 +/
      3.9% to 13.5 +/- 1.9% (P < 0.05). At 0.01 MUM/L, GSK 576371 inhibited
      spontaneous bladder overactivity by 50%, but inhibited carbachol-elicited
      contractions force by just 25%. CONCLUSIONS: These data suggest that Rho-kinase
      regulation of myosin light chain phosphorylation contributes to the spontaneous
      detrusor activity induced by obstruction. This finding could have therapeutic
      implications by providing another therapeutic option for myogenic, overactive
      bladder.

PMID- 24033564
TI  - The effect of flow rate and agitation technique on irrigant extrusion ex vivo.
AB  - AIM: To evaluate (i) the effect of irrigant flow rate, needle type, needle
      insertion depth and apical constriction diameter and (ii) the effect of
      ultrasonic, sonic and manual dynamic agitation on irrigant extrusion using a
      recently introduced method. METHODOLOGY: Thirty-two human teeth with a straight
      root canal were prepared to size 35, 0.06 taper and assigned to group A or B. The
      apical constriction diameter was 0.15-0.25 mm. Specimens were mounted on a
      plastic vial filled with distilled water to simulate a periapical lesion. A point
      conductivity probe was used to determine the volume of irrigant extruded into the
      vial. Within group A, NaOCl was delivered at 0.14 or 0.26 mL s(-1) by an open
      ended or a closed-ended needle at 1 or 3 mm short of working length (WL). In
      group B, NaOCl was agitated at high or low power either by an ultrasonically or
      sonically oscillating instrument inserted at 1 or 3 mm short of WL or by manual
      push-pull strokes of a gutta-percha cone. Results were analysed by repeated
      measures anovas, at 0.05 significance. RESULTS: An increase in the flow rate
      resulted in increased extrusion (P < 0.001). The open-ended needle extruded
      significantly more irrigant than the closed-ended (P < 0.001). Extrusion
      decreased as needles moved away from WL (P < 0.001). The effect of apical
      constriction diameter was not significant (P > 0.454). Manual dynamic agitation
      extruded significantly more irrigant than sonic and ultrasonic agitation (P <
      0.001). CONCLUSIONS: Irrigant flow rate, needle type and insertion depth and
      agitation technique had a significant effect on extrusion.

PMID- 24033565
TI  - Turnover of Se in adequately fed chickens using Se-75 as a tracer.
AB  - Inorganic selenium (Se) in the form of selenite is applied to livestock to avoid
      Se deficiency. Selenite is, however, an artificial Se source in diets of
      unsupplemented chickens. It is therefore hypothesized that organic Se sources,
      such as Se-enriched yeast and wheat, could be a more suitable Se supply in animal
      nutrition, although information on the transition of Se from organic Se sources
      in fast-growing chickens is scarce. In this work, chickens were fed a low Se diet
      (0.27 +/- 0.01 mg Se/kg, Se-enriched yeast) until 20 days of age, after which the
      Se concentration was increased to maximum concentration allowed by the poultry
      industry in Europe (0.5 p.p.m. Se). At the same time, a daily contribution of
      carrier-free (75)Se tracer from labelled wheat was administered from day 20 to
      27. The chickens showed S and Se homeostasis, as the concentration of S and Se in
      liver, blood or kidney remained about constant, and steady state of S and Se in
      the other organs was reached 1 day after the diet shift. The uptake of (75)Se was
      readily seen in all organs. After 1 week, the depuration of the (75)Se tracer was
      followed, and biological half-lives and retention in individual organs were
      determined. The shortest biological half-lives were observed in major metabolic
      organs, the liver, kidney and pancreas with half-lives close to 4 days. There was
      a significant (p < 0.05) uptake in lung, brain and muscle that reached steady
      state when the administration of (75)Se was terminated. The half-life of (75)Se
      in heart was 9 days and 7 days in blood. The longest half-lives were observed in
      muscle (12 days), brain and lungs (13 days). All half-lives were shorter than in
      Se deplete animals.

PMID- 24033566
TI  - Hyperforin inhibits cell proliferation and differentiation in mouse embryonic
      stem cells.
AB  - OBJECTIVES: Hyperforin, a phloroglucinol derivative of St. John's Wort, has been
      identified as the major molecule responsible for this plant's products anti
      depressant effects. It can be expected that exposure to St. John's Wort during
      pregnancy occurs with some frequency although embryotoxic or teratogenic effects
      of St. John's Wort and hyperforin have not yet been experimentally examined in
      detail. In this study, to determine any embryotoxic effects of hyperforin, we
      have attempted to determine whether hyperforin affects growth and survival
      processes of employing mouse embryonic stem (mES) cells (representing embryonic
      tissue) and fibroblasts (representing adult tissues). MATERIALS AND METHODS: We
      used a modified embryonic stem cell test, which has been validated as an in vitro
      developmental toxicity protocol, mES cells, to assess embryotoxic potential of
      chemicals under investigation. RESULTS: We have identified that high
      concentrations of hyperforin inhibited mouse ES cell population growth and
      induced apoptosis in fibroblasts. Under our cell culture conditions, ES cells
      mainly differentiated into cardiomyocytes, although various other cell types were
      also produced. In this condition, hyperforin affected ES cell differentiation
      into cardiomyocytes in a dose-dependent manner. Analysis of tissue-specific
      marker expression also revealed that hyperforin at high concentrations partially
      inhibited ES cell differentiation into mesodermal and endodermal lineages.
      CONCLUSIONS: Hyperforin is currently used in the clinic as a safe and effective
      antidepressant. Our data indicate that at typical dosages it has only a low risk
      of embryotoxicity; ingestion of large amounts of hyperforin by pregnant women,
      however, may pose embryotoxic and teratogenic risks.

PMID- 24033567
TI  - Nutrient displacement associated with walnut supplementation in men.
AB  - BACKGROUND: Dietary guidance issued by various global government agencies
      recommends nut consumption within the context of a healthy-eating pattern. Nuts
      are nutrient dense and may promote nutrient adequacy. As an energy-dense food,
      nuts must replace other foods in the diet to prevent an excess of calories.
      METHODS: We evaluated how recommending the inclusion of walnuts (75 g day(-1) )
      in the diet affected energy and nutrient intake in men (45-75 years; mean body
      mass index = 27.6 kg m(-2) ; n = 19) at risk for developing prostate cancer.
      Guidance was provided about incorporating walnuts isocalorically in a healthy
      diet. Three-day food records and body weight were collected at baseline and after
      two 8-week diet periods (usual versus walnut supplement diets). RESULTS: Energy
      intake on the walnut supplement diet exceeded the usual diet, although body
      weight was maintained. Energy intake was lower on the actual walnut supplement
      diet than the calculated walnut diet [10,865 kJ (2595 kcal) versus 11,325 kJ
      (2705 kcal) per day, respectively] and contributed 23% less energy than 75 g of
      walnuts. Approximately, 86% and 85% of the total fat and saturated fatty acids
      from walnuts were not displaced, whereas the increase in fibre from the usual
      diet to the actual walnut supplement diet represented less than one-half (39%) of
      the fibre provided by 75 g of walnuts. Walnuts were substituted, in part, for
      other foods, and the nutrient profile of the diet was improved, however, the
      beneficial effect of walnuts on the diet quality was not optimized. CONCLUSIONS:
      Individuals do not optimally implement food-based guidance. Consequently,
      nutrition professionals play a key role in teaching the implementation of food
      based recommendations.

PMID- 24033568
TI  - Descriptions of euthanasia as social representations: comparing the views of
      Finnish physicians and religious professionals.
AB  - In many western societies health professionals play a powerful role in people's
      experiences of dying. Religious professionals, such as pastors, are also
      confronted with the issues surrounding death and dying in their work. It is
      therefore reasonable to assume that the ways in which death-related topics, such
      as euthanasia, are constructed in a given culture are affected by the views of
      these professionals. This qualitative study addresses the ways in which Finnish
      physicians and religious professionals perceive and describe euthanasia and
      conceptualises these descriptions and views as social representations. Almost all
      the physicians interviewed saw that euthanasia does not fit the role of a
      physician and anchored it to different kinds of risks such as the slippery slope.
      Most of the religious and world-view professionals also rejected euthanasia. In
      this group, euthanasia was rejected on the basis of a religious moral code that
      forbids killing. Only one of the religious professionals - the freethinker with
      an atheist world-view - accepted euthanasia and described it as a personal
      choice, as did the one physician interviewed who accepted it. The article shows
      how the social representations of euthanasia are used to protect professional
      identities and to justify their expert knowledge of death and dying. 

PMID- 24033569
TI  - Neurocognitive consequences of socioeconomic disparities: the intersection of
      cognitive neuroscience and public health.

PMID- 24033570
TI  - Associations between children's socioeconomic status and prefrontal cortical
      thickness.
AB  - Childhood socioeconomic status (SES) predicts executive function performance and
      measures of prefrontal cortical function, but little is known about its
      anatomical correlates. Structural MRI and demographic data from a sample of 283
      healthy children from the NIH MRI Study of Normal Brain Development were used to
      investigate the relationship between SES and prefrontal cortical thickness.
      Specifically, we assessed the association between two principal measures of
      childhood SES, family income and parental education, and gray matter thickness in
      specific subregions of prefrontal cortex and on the asymmetry of these areas.
      After correcting for multiple comparisons and controlling for potentially
      confounding variables, parental education significantly predicted cortical
      thickness in the right anterior cingulate gyrus and left superior frontal gyrus.
      These results suggest that brain structure in frontal regions may provide a
      meaningful link between SES and cognitive function among healthy, typically
      developing children. 

PMID- 24033571
TI  - Higher education is an age-independent predictor of white matter integrity and
      cognitive control in late adolescence.
AB  - Socioeconomic status is an important predictor of cognitive development and
      academic achievement. Late adolescence provides a unique opportunity to study how
      the attainment of socioeconomic status (in the form of years of education)
      relates to cognitive and neural development, during a time when age-related
      cognitive and neural development is ongoing. During late adolescence it is
      possible to disambiguate age- and education-related effects on the development of
      these processes. Here we assessed the degree to which higher educational
      attainment was related to performance on a cognitive control task, controlling
      for age. We then used diffusion tensor imaging (DTI) to assess the degree to
      which white matter microstructure might mediate this relationship. When covarying
      age, significant associations were found between educational attainment and
      fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) and
      cingulum bundle (CB). Further, when covarying age, FA in these regions was
      associated with cognitive control. Finally, mediation analyses revealed that the
      age-independent association between educational attainment and cognitive control
      was completely accounted for by FA in these regions. The uncinate fasciculus, a
      late-myelinated control region not implicated in cognitive control, did not
      mediate this effect. 

PMID- 24033573
TI  - Socioeconomic status and functional brain development - associations in early
      infancy.
AB  - Socioeconomic status (SES) impacts on both structural and functional brain
      development in childhood, but how early its effects can be demonstrated is
      unknown. In this study we measured resting baseline EEG activity in the gamma
      frequency range in awake 6-9-month-olds from areas of East London with high
      socioeconomic deprivation. Between-subject comparisons of infants from low- and
      high-income families revealed significantly lower frontal gamma power in infants
      from low-income homes. Similar power differences were found when comparing
      infants according to maternal occupation, with lower occupational status groups
      yielding lower power. Infant sleep, maternal education, length of gestation, and
      birth weight, as well as smoke exposure and bilingualism, did not explain these
      differences. Our results show that the effects of socioeconomic disparities on
      brain activity can already be detected in early infancy, potentially pointing to
      very early risk for language and attention difficulties. This is the first study
      to reveal region-selective differences in functional brain development associated
      with early infancy in low-income families. 

PMID- 24033572
TI  - What are the links between maternal social status, hippocampal function, and HPA
      axis function in children?
AB  - The association of parental social status with multiple health and achievement
      indicators in adulthood has driven researchers to attempt to identify mechanisms
      by which social experience in childhood could shift developmental trajectories.
      Some accounts for observed linkages between parental social status in childhood
      and health have hypothesized that early stress exposure could result in chronic
      disruptions in hypothalamic-pituitary-adrenal (HPA) axis activation, and that
      this activation could lead to long-term changes. A robust literature in adult
      animals has demonstrated that chronic HPA axis activation leads to changes in
      hippocampal structure and function. In the current study, consistent with studies
      in animals, we observe an association between both maternal self-rated social
      status and hippocampal activation in children and between maternal self-rated
      social status and salivary cortisol in children. 

PMID- 24033574
TI  - Childhood poverty, chronic stress, and young adult working memory: the protective
      role of self-regulatory capacity.
AB  - Prior research shows that childhood poverty as well as chronic stress can damage
      children's executive functioning (EF) capacities, including working memory.
      However, it is also clear that not all children suffer the same degree of adverse
      consequences from risk exposure. We show that chronic stress early in life (ages
      9-13) links childhood poverty from birth to age 13 to young adult working memory.
      However, 9-year-olds high in self-regulatory capacity, assessed by a standard
      delay of gratification protocol, are protected from such insults. Self-regulatory
      skills may afford the developing prefrontal cortex some protection from childhood
      poverty. 

PMID- 24033575
TI  - Linking childhood poverty and cognition: environmental mediators of non-verbal
      executive control in an Argentine sample.
AB  - Tests of attentional control, working memory, and planning were administered to
      compare the non-verbal executive control performance of healthy children from
      different socioeconomic backgrounds. In addition, mediations of several
      sociodemographic variables, identified in the literature as part of the
      experience of child poverty, between socioeconomic status and cognitive
      performance were assessed. Results show: (1) significant differences in
      performance between groups in most dependent variables analyzed - however, not in
      all variables associated with attentional control domains; (2) significant
      indirect effects of literacy activities on working memory and fluid processing
      domains, as well as computer resources effects on fluid processing; and (3)
      marginal indirect effects of computer resources on attentional control and
      working memory domains. These findings extend analysis of the impact of poverty
      on the development of executive control, through information based on the
      assessment of combined neurocognitive paradigms and the identification of
      specific environmental mediators. 

PMID- 24033576
TI  - Commentary: neurocognitive consequences of socioeconomic disparities.

PMID- 24033577
TI  - Blocking a redundant cue: what does it say about preschoolers' causal competence?
AB  - The current study investigates the degree to which preschoolers can engage in
      causal inferences in a blocking paradigm, a paradigm in which a cue is
      consistently linked with a target, either alone (A-T) or paired with another cue
      (AB-T). Unlike previous blocking studies with preschoolers, we manipulated the
      causal structure of the events without changing the specific contingencies. In
      particular, cues were said to be either potential causes (prediction condition),
      or they were said to be potential effects (diagnosis condition). The causally
      appropriate inference is to block the redundant cue B when it is a potential
      cause of the target, but not when it is a potential effect. Findings show a stark
      difference in performance between preschoolers and adults: While adults blocked
      the redundant cue only in the prediction condition, children blocked the
      redundant cue indiscriminately across both conditions. Therefore, children, but
      not adults, ignored the causal structure of the events. These findings challenge
      a developmental account that attributes sophisticated machinery of causal
      reasoning to young children. 

PMID- 24033578
TI  - The effect of early visual deprivation on the development of face detection.
AB  - The expertise of adults in face perception is facilitated by their ability to
      rapidly detect that a stimulus is a face. In two experiments, we examined the
      role of early visual input in the development of face detection by testing
      patients who had been treated as infants for bilateral congenital cataract.
      Experiment 1 indicated that, at age 9 to 20, patients' accuracy and response
      times on a Mooney face detection task were normal. Experiment 2 revealed that the
      neural mechanisms underlying face detection in a similar group of adult patients
      are abnormal: the amplitude of both the P100 and N170 event-related potential
      were larger in patients than in visually normal controls, and the extent of
      augmentation was related to the duration of deprivation. Thus, early visual
      experience is necessary for the establishment of normal neural networks for face
      detection; abnormalities at these early processing stages may contribute to the
      deficits we previously reported in configural face processing for this patient
      cohort. 

PMID- 24033579
TI  - Neural responses to witnessing peer rejection after being socially excluded: fMRI
      as a window into adolescents' emotional processing.
AB  - During adolescence, concerns about peer rejection and acceptance become
      increasingly common. Adolescents regularly experience peer rejection firsthand
      and witness these behaviors among their peers. In the current study, neuroimaging
      techniques were employed to conduct a preliminary investigation of the affective
      and cognitive processes involved in witnessing peer acceptance and rejection -
      specifically when these witnessed events occur in the immediate aftermath of a
      firsthand experience with rejection. During an fMRI scan, 23 adolescents
      underwent a simulated experience of firsthand peer rejection. Then, immediately
      following this experience they watched as another adolescent was ostensibly first
      accepted and then rejected. Findings indicated that in the immediate aftermath of
      being rejected by peers, adolescents displayed neural activity consistent with
      distress when they saw another peer being accepted, and neural activity
      consistent with emotion regulation and mentalizing (e.g. perspective-taking)
      processes when they saw another peer being rejected. Furthermore, individuals
      displaying a heightened sensitivity to firsthand rejection were more likely to
      show neural activity consistent with distress when observing a peer being
      accepted. Findings are discussed in terms of how witnessing others being accepted
      or rejected relates to adolescents' interpretations of both firsthand and
      observed experiences with peers. In addition, the potential impact that witnessed
      events might have on the broader perpetuation of bullying at this age is also
      considered. 

PMID- 24033580
TI  - Learning to look: probabilistic variation and noise guide infants' eye movements.
AB  - Young infants have demonstrated a remarkable sensitivity to probabilistic
      relations among visual features (Fiser & Aslin, 2002; Kirkham et al., 2002).
      Previous research has raised important questions regarding the usefulness of
      statistical learning in an environment filled with variability and noise, such as
      an infant's natural world. In an eye-tracking experiment, 8-month-old infants
      viewed sequences of spatio-temporal events with three different transitional
      probabilities (1.0-Deterministic, 0.75-High probability, and 0.5-Low
      probability). Across two between-subjects conditions, the sequences were
      presented with or without competing visual distracters. Results show that as
      transitional probability decreased, infants distributed less attention to the
      predictable locations and their anticipations were less often correct. With no
      distraction, infants had faster saccadic latencies to the high probability
      events; however, with distracters present in the stimulus environment, infants'
      eye movements shifted to favour the deterministic relations. These findings
      suggest that infants integrate multiple sources of variability to guide visual
      attention and facilitate the detection and learning of statistically reliable
      events. 

PMID- 24033581
TI  - Mapping subcortical brain maturation during adolescence: evidence of hemisphere-
      and sex-specific longitudinal changes.
AB  - Early to mid-adolescence is an important developmental period for subcortical
      brain maturation, but longitudinal studies of these neurodevelopmental changes
      are lacking. The present study acquired repeated magnetic resonance images from
      60 adolescent subjects (28 female) at ages 12.5 and 16.5 years to map changes in
      subcortical structure volumes. Automated segmentation techniques optimized for
      longitudinal measurement were used to delineate volumes of the caudate, putamen,
      nucleus accumbens, pallidum, hippocampus, thalamus and the whole brain. Amygdala
      volumes were described using manual tracing methods. The results revealed
      heterogeneous maturation across the regions of interest (ROIs), and change was
      differentially moderated by sex and hemisphere. The caudate, thalamus and putamen
      declined in volume, more for females relative to males, and decreases in the
      putamen and thalamus were greater in the left hemisphere. The pallidum increased
      in size, but more so in the left hemisphere. While the left nucleus accumbens
      increased in size, the right accumbens decreased in size over the follow-up
      period. Increases in hippocampal volume were greater in the right hemisphere.
      While amygdala volume did not change over time, the left hemisphere was
      consistently larger than the right. These results suggest that subcortical brain
      development from early to middle adolescence is characterized by striking
      hemispheric specialization and sexual dimorphisms, and provide a framework for
      interpreting normal and abnormal changes in cognition, affect and behavior.
      Moreover, the differences in findings compared to previous cross-sectional
      research emphasize the importance of within-subject assessment of brain
      development during adolescence. 

PMID- 24033582
TI  - Rhizobium leguminosarum is the symbiont of lentils in the Middle East and Europe
      but not in Bangladesh.
AB  - Lentil is the oldest of the crops that have been domesticated in the Fertile
      Crescent and spread to other regions during the Bronze Age, making it an ideal
      model to study the evolution of rhizobia associated with crop legumes.
      Housekeeping and nodulation genes of lentil-nodulating rhizobia from the region
      where lentil originated (Turkey and Syria) and regions to which lentil was
      introduced later (Germany and Bangladesh) were analyzed to determine their
      genetic diversity, population structure, and taxonomic position. There are four
      different lineages of rhizobia associated with lentil nodulation, of which three
      are new and endemic to Bangladesh, while Mediterranean and Central European
      lentil symbionts belong to the Rhizobium leguminosarum lineage. The endemic
      lentil grex pilosae may have played a significant role in the origin of these new
      lineages in Bangladesh. The presence of R. leguminosarum with lentil at the
      center of origin and in countries where lentil was introduced later suggests that
      R. leguminosarum is the original symbiont of lentil. Lentil seeds may have played
      a significant role in the initial dispersal of this Rhizobium species within the
      Middle East and on to other countries. Nodulation gene sequences revealed a high
      similarity to those of symbiovar viciae.

PMID- 24033583
TI  - Population genetic analyses provide insights on the introduction pathway and
      spread patterns of the North American forest pathogen Heterobasidion irregulare
      in Italy.
AB  - A population genetics approach is used to identify the most likely introduction
      site and introduction pathway for the North American forest pathogen
      Heterobasidion irregulare using 101 isolates from six sites in Italy and 34
      isolates from five sites in North America. Diversity indices based on sequences
      from ten loci indicate the highest diversity in Italy is found in
      Castelfusano/Castelporziano and that diversity progressively decreases with
      increasing distance from that site. AMOVA, Bayesian clustering and principal
      coordinates analyses based on 12 SSR loci indicate high levels of gene flow among
      sites, high frequency of admixing, and fail to identify groups of genotypes
      exclusive to single locations. Cumulatively, these analyses suggest the current
      infestation is the result of multiple genotypes expanding their range from a
      single site. Based on two sequenced loci, a single source site in North America
      could provide enough variability to explain the variability observed in Italy.
      These results support the notion that H. irregulare was introduced originally in
      Castelporziano: because Castelporziano has been sealed off from the rest of the
      world for centuries except for a camp set up by the US military in 1944, we
      conclude the fungus may have been transported in infected wood used by the
      military. Finally, spatial autocorrelation analyses using SSR data indicate a
      significant under-dispersion of alleles up to 0.5-10 km, while a significant
      overdispersion of alleles was detected at distances over 80 km: these ranges can
      be used to make predictions on the likely dispersal potential of the invasive
      pathogen.

PMID- 24033585
TI  - Comment on "protective arms of the renin-angiotensin system in neurological
      disease": Reply.

PMID- 24033584
TI  - Three-dimensional volumetry in 107 normal livers reveals clinically relevant
      inter-segment variation in size.
AB  - BACKGROUND: The anatomic resection of Couinaud's segments is one of the key
      techniques in liver surgery. However, the territories and volumes of the eight
      segments are not adequately assessed based on portal branching. METHODS: Three
      dimensional (3D) perfusion-based volumetry was performed in 107 normal livers.
      Based on Couinaud classification, the portal branches were identified and the
      volumes of each segment were calculated. The relationships between branching
      patterns of the portal veins and segmental volumes were assessed. RESULTS: In
      descending order of volume, median volumes of segments VIII, VII, IV, V, III, VI,
      II and I were recorded. Segment VIII was the largest, accounting for a median of
      26.1% (range: 11.1-38.0%) of total liver volume (TLV), whereas segments II and
      III each represented <10% of TLV. In 69.2% of subjects, the portal branches of
      segment V diverged from the trunk of the branches of segment VIII. No
      relationship was found between branching type and segment volume. CONCLUSIONS:
      The territories and volumes of Couinaud's segments vary among segments, as well
      as among individuals. Detailed 3D volumetry is useful for preoperative
      evaluations of the dissection line and of future liver remnant volume in anatomic
      segmentectomy.

PMID- 24033586
TI  - Alcohol consumption, heavy drinking, and mortality: rethinking the j-shaped
      curve.
AB  - BACKGROUND: High average daily consumption of alcohol has been associated with
      elevated mortality risk, but more moderate consumption, relative to abstinence,
      has been associated with reduced mortality risk. However, average daily
      consumption can be complicated to assess, limiting its usefulness in both
      research and clinical practice. There are also concerns that average consumption
      fails to capture the risk associated with certain drinking patterns, such as
      heavy episodic drinking. This study assessed mortality associated with drinking
      pattern, operationalized as the frequency of both heavy and nonheavy drinking
      occasions. METHODS: Data from the 1997 to 2001 administrations of the National
      Health Interview Survey (NHIS; n = 111,511) were paired with the current release
      of the NHIS Linked Mortality Files, which provided mortality follow-up data
      through the end of 2006. We estimated the impact of drinking pattern on all-cause
      mortality, operationalized as the frequency of heavy (5+ drinks) and nonheavy (<5
      drinks) drinking occasions. Other covariates in the model included survey wave,
      sex, age, race/ethnicity, ratio of family income to poverty threshold,
      educational attainment, body mass index, and smoking status. RESULTS: Over a
      third of past-year drinkers reported heavy drinking. Mortality risk increased
      steadily as heavy drinking frequency increased; daily heavy drinkers exhibited an
      almost 2-fold risk of death compared with abstainers (p < 0.001). Regular
      nonheavy drinking was associated with decreased mortality, similar to the "J
      shaped curve" highlighted in past research on alcohol mortality; this potential
      protective effect peaked around 2 nonheavy occasions per week. CONCLUSIONS: Any
      heavy drinking likely elevates mortality risk, and substantial health benefits
      could be realized by reducing heavy drinking occasions or limiting overall
      drinking. Heavy and nonheavy drinking frequencies are valid targets for clinical
      screening and could be helpful in assessing risk and promoting less harmful
      drinking behavior.

PMID- 24033587
TI  - Predictive performance of reported population pharmacokinetic models of
      vancomycin in Chinese adult patients.
AB  - WHAT IS KNOWN AND OBJECTIVE: There are numerous studies on population
      pharmacokinetics of vancomycin in adult patients. However, there is no such
      research for Chinese adult patients. This study was conducted to evaluate the
      predictive performance of reported population pharmacokinetic models of
      vancomycin in Chinese adult patients and to identify some models appropriate for
      our population. METHODS: A literature search was conducted in PubMed to obtain
      the population pharmacokinetic models of vancomycin published between December
      2010 and September 2012. The models were assessed using concentration data
      collected from Chinese patients for external validation. Models with relatively
      poor predictability were excluded from further analysis. The performance of the
      remaining models was evaluated in patients with different levels of creatinine
      clearance, age, body weight and sex by Bayesian method. This method was also used
      to compare the predictive performance based on peak concentration and trough
      concentration and the predictability based on different number of observed
      concentrations. RESULTS: One hundred and sixty-five blood concentrations from 72
      Chinese adult patients were collected retrospectively to serve as the test data
      set. The evaluated models included all those reported in the seven publications
      reviewed by Marsot et al. and three other studies published after December 2010.
      Three models with poor performance on external validation were excluded from the
      next Bayesian analysis. The distribution of covariates in the model building data
      set had an important effect on prediction. The predictability based on
      peak/trough concentration was similar among the evaluated models, and no
      significant difference was found using our data set except for Roberts' model. As
      expected, an increased number of samples improved the performance of the Bayesian
      prediction. WHAT IS NEW AND CONCLUSION: With our data set, the performance of the
      evaluated models varied. The characteristics of the patient population and
      distribution of covariates should be given more consideration when choosing a
      model to predict blood concentrations. The model developed by Purwonugroho et al.
      using a data set from patients similar to ours is appropriate for Bayesian dose
      predictions for vancomycin concentrations in our population of Chinese adult
      patients.

PMID- 24033588
TI  - Maternal suicide is the leading cause of pregnancy-related deaths in Sri Lanka.

PMID- 24033589
TI  - Impact of the 2009 Taiwan tobacco hazards prevention act on smoking cessation.
AB  - AIMS: In January 2009, the government of Taiwan amended the 1997 Tobacco Hazards
      Prevention Act by extending smoke-free areas to include almost all enclosed work
      places and public places, adding graphic health warnings to cigarette packages,
      totally banning tobacco advertisements, promotion and sponsorship and increasing
      tobacco taxes. This study examined the impact of the 2009 amended Act on smoking
      cessation in Taiwan. DESIGN: Taiwan Adult Tobacco Surveys 2007 and 2010, each
      with a nationally representative sample of adults aged 18 years and older (n = 16
      588, and n = 16 295, respectively). PARTICIPANTS: All recent active smokers
      (current smokers plus former smokers who quit smoking within the past 12 months)
      were used for the analyses (n = 3783 in 2007, and n = 2777 in 2010).
      MEASUREMENTS: Quit attempt rate and annual cessation rate (defined as having
      succeeded in quitting for at least 3 months) among recent active smokers were
      compared between the pre-Act (2007) and post-Act (2010) periods. FINDINGS: The
      quit attempt rate increased significantly from 39.4% in 2007 to 42.9% in 2010.
      The annual cessation rate increased significantly from 7.1 to 8.9%. A
      multivariate analysis, controlling for demographic characteristics, showed that
      the implementation of the 2009 Act was associated with an increase in the quit
      attempt rate [odds ratio (OR) = 1.14; 95% confidence interval (CI) = 1.03-1.25]
      and the annual cessation rate (OR = 1.28; 95% CI = 1.08-1.53). CONCLUSIONS: The
      comprehensive tobacco control programme introduced in 2009 in Taiwan, which
      combined smoke-free legislation with a tobacco tax increase, graphic health
      warning labels and a total ban on tobacco advertisements, was associated with
      increases in quit attempt rate and annual cessation rate.

PMID- 24033590
TI  - Distal limb desensitisation following analgesia of the digital flexor tendon
      sheath in horses using four different techniques.
AB  - REASONS FOR PERFORMING STUDY: Controversy exists about the desensitisation
      obtained after diagnostic analgesia of the digital flexor tendon sheath (DFTS)
      during lameness examinations. OBJECTIVES: To determine whether DFTS analgesia
      results in inadvertent desensitisation of the palmar/plantar digital nerves and
      whether this depends on the injection technique used. STUDY DESIGN: Crossover
      experimental study. METHODS: The DFTS of 9 horses were injected with local
      anaesthetic solution and radiodense contrast medium using one of the following
      techniques: Proximal (at lateral proximal recess of the DFTS), Axial (axial to
      the lateral proximal sesamoid bone), Base (at base of the lateral proximal
      sesamoid bone), and Distal (at palmar/plantar mid-pastern). In total, 72
      injections were performed. Skin desensitisation at the heel bulbs was tested with
      a dynamometer before and at 15, 30, 90 and 120 min after injection. RESULTS:
      Overall, complete desensitisation of a heel bulb at one or more time points after
      injection occurred in 22 limbs (30.6%). An additional 7 limbs were partially
      desensitised. Complete skin desensitisation occurred in 10, 3, 4 and 5 limbs
      using the Proximal, Axial, Base and Distal techniques respectively. Significant
      differences between techniques were only found at T30. The probability of skin
      desensitisation at the heel bulbs was 4 times higher when using the Proximal
      compared with the Axial and Base techniques in the forelimbs, and 3 times higher
      compared with the Axial and Distal techniques in the hindlimbs. Skin
      desensitisation nearly always occurred exclusively on the lateral heel bulb.
      Bilateral desensitisation only occurred in 5 limbs. CONCLUSIONS: Anaesthesia of
      the palmar/plantar digital nerves with distal limb desensitisation often occurs
      after DFTS analgesia. A higher chance of desensitisation exists when injecting
      the proximal DFTS recess. It is advisable to verify skin sensitivity at the heel
      bulbs after DFTS analgesia to avoid false interpretations about the origin of
      pain causing lameness.

PMID- 24033591
TI  - Accuracy of acoustic respiration rate monitoring in pediatric patients.
AB  - BACKGROUND: Rainbow acoustic monitoring (RRa) utilizes acoustic technology to
      continuously and noninvasively determine respiratory rate from an adhesive sensor
      located on the neck. OBJECTIVE: We sought to validate the accuracy of RRa, by
      comparing it to capnography, impedance pneumography, and to a reference method of
      counting breaths in postsurgical children. METHODS: Continuous respiration rate
      data were recorded from RRa and capnography. In a subset of patients,
      intermittent respiration rate from thoracic impedance pneumography was also
      recorded. The reference method, counted respiratory rate by the retrospective
      analysis of the RRa, and capnographic waveforms while listening to recorded
      breath sounds were used to compare respiration rate of both capnography and RRa.
      Bias, precision, and limits of agreement of RRa compared with capnography and RRa
      and capnography compared with the reference method were calculated. Tolerance and
      reliability to the acoustic sensor and nasal cannula were also assessed. RESULTS:
      Thirty-nine of 40 patients (97.5%) demonstrated good tolerance of the acoustic
      sensor, whereas 25 of 40 patients (62.5%) demonstrated good tolerance of the
      nasal cannula. Intermittent thoracic impedance produced erroneous respiratory
      rates (>50 b.min(-1) from the other methods) on 47% of occasions. The bias +/- SD
      and limits of agreement were -0.30 +/- 3.5 b.min(-1) and -7.3 to 6.6 b.min(-1)
      for RRa compared with capnography; -0.1 +/- 2.5 b.min(-1) and -5.0 to 5.0 b.min(
      1) for RRa compared with the reference method; and 0.2 +/- 3.4 b.min(-1) and -6.8
      to 6.7 b.min(-1) for capnography compared with the reference method. CONCLUSIONS:
      When compared to nasal capnography, RRa showed good agreement and similar
      accuracy and precision but was better tolerated in postsurgical pediatric
      patients.

PMID- 24033592
TI  - Design and evaluation of radiolabeled tracers for tumor imaging.
AB  - The growing understanding of tumor biology and the identification of tumor
      specific genetic and molecular alterations, such as the overexpression of
      membrane receptors and other proteins, allows for personalization of patient
      management using targeted therapies. However, this puts stringent demands on the
      diagnostic tools used to identify patients who are likely to respond to a
      particular treatment. Radionuclide molecular imaging is a promising noninvasive
      method to visualize and characterize the expression of such targets. A number of
      different proteins, from full-length antibodies and their derivatives to small
      scaffold proteins and peptide receptor-ligands, have been applied to molecular
      imaging, each demonstrating strengths and weaknesses. Here, we discuss the
      concept of molecular targeting and, in particular, molecular imaging of cancer
      associated targets. Additionally, we describe important biotechnological
      considerations and desired features when designing and developing tracers for
      radionuclide molecular imaging. 

PMID- 24033593
TI  - Purification and characterization of a protein with antifungal,
      antiproliferative, and HIV-1 reverse transcriptase inhibitory activities from
      small brown-eyed cowpea seeds.
AB  - A 36-kDa protein, with an N-terminal sequence highly homologous to
      polygalacturonase (PG) inhibiting proteins, was isolated from small brown-eyed
      cowpea seeds. The protein was unadsorbed on diethylaminoethyl cellulose but
      adsorbed on both Affi-gel blue gel and SP-sepharose. It inhibited mycelial growth
      in the fungus Mycosphaerella arachidicola with an half-maximal (50%) inhibitory
      concentration (IC50 ) of 3.3 uM. It reduced [methyl-(3) H] thymidine
      incorporation into MBL2 lymphoma and L1210 leukemia cells with an IC50 of 7.4 and
      5.4 uM, respectively. It inhibited human immunodeficiency virus type 1 (HIV-1)
      reverse transcriptase with an IC50 of 12.9 uM. However, it did not inhibit PG.
      The potent antifungal and antitumor activities of the protein suggest that it can
      be developed into an antifungal agent for combating M. arachidicola invasion in
      crops and an agent for cancer therapy in humans.

PMID- 24033594
TI  - Development of a novel fluorescent protein construct by genetically fusing green
      fluorescent protein to the N-terminal of aspartate dehydrogenase.
AB  - We developed a fluorescent protein construct by genetically fusing green
      fluorescent protein (GFP) to aspartate dehydrogenase from Thermotoga maritima.
      The fusion protein was cloned, heterologously expressed in Escherichia coli
      cells, and purified by Ni-chelate affinity chromatography. It was then introduced
      into a measurement cuvette to monitor its fluorescence signal. Aspartate
      dehydrogenase functioned as the biorecognition element, and aspartate-induced
      conformational change was converted to a fluorescence signal by GFP. The
      recombinant protein responded to l-aspartate (l-Asp) linearly within the
      concentration range of 1-50 mM, and it was capable of giving a fluorescence
      signal in 1 Min. Although a linear response was also observed for l-Glu, the
      fluorescence signal was 2.7 times lower than that observed for l-Asp. In the
      present study, we describe two novelties: development of a genetically encoded
      fluorescent protein construct for monitoring of l-Asp in vitro, and employment of
      aspartate dehydrogenase scaffold as a biorecognition element. A few genetically
      encoded amino-acid biosensors have been described in the literature, but to our
      knowledge, a protein has not been constructed solely for determination of l-Asp.
      Periplasmic ligand binding proteins offer high binding affinity in the micromolar
      range, and they are frequently used as biorecognition elements. Instead of
      choosing a periplasmic l-Asp binding protein, we attempted to use the substrate
      specificity of aspartate dehydrogenase enzyme.

PMID- 24033595
TI  - Expression and characterization of Rv0447c product, potentially the
      methyltransferase involved in tuberculostearic acid biosynthesis in Mycobacterium
      tuberculosis.
AB  - In this study, a previously uncharacterized gene (Rv0447c) of Mycobacterium
      tuberculosis, designated as an unknown fatty-acid methyltransferase (ufaA1), was
      cloned, expressed in Escherichia coli, and purified. The biochemical
      characterization of the purified protein (UfaA1) showed it to be a
      methyltransferase that catalyzes biosynthesis of the tuberculostearic acid (10
      methylstearic-acid, TSA), a significant constituent lipid of the mycobacterial
      cell wall and a clinical marker of the disease. Here, we show that UfaA1
      transfers the methyl group from S-adenosyl-l-methionine (SAM) to the double bond
      of oleic acid in phosphatidylethanolamine or phosphatidylcholine to produce TSA.
      Optimal activity was obtained between pH 7.0 and pH 8.0. The methyltransferase
      activity of UfaA1 was severely inhibited by S-adenosyl-l-homocysteine. The Km
      values for dioleyl phosphatidylethanolamine, SAM, and nicotinamide adenine
      dinucleotide phosphate were 14, 13, and 83 uM, respectively, with Vmax of 1.3-1.6
      nmol/Min. These results identify the Rv0447c gene product of M. tuberculosis as
      the methyltransferase that catalyzes the biosynthesis of TSA. This provides new
      information in mycobacterial cell wall synthesis.

PMID- 24033596
TI  - Inhibitory potential of Grifola frondosa bioactive fractions on alpha-amylase and
      alpha-glucosidase for management of hyperglycemia.
AB  - This study examined the inhibitory effects of Grifola frondosa (GF), a medicinal
      mushroom popularly consumed in traditional medicine and health food, on digestive
      enzymes related to type 2 diabetes; chemical profiles and inhibitory kinetics of
      its bioactive fractions were also analyzed. Results showed that all GF extracts
      showed weak anti-alpha-amylase activity; however, strong anti-alpha-glucosidase
      activity was noted on GF n-hexane extract (GF-H). Further fractionation confirmed
      that compared with acarbose (a commercial alpha-glucosidase inhibitor), the
      nonpolar fraction of GF possessed a stronger anti-alpha-glucosidase activity but
      a weaker anti-alpha-amylase activity. These activities were not derived from
      ergosterol and ergosterol peroxide, two major compounds of this fraction. The
      inhibitory kinetics of GF-H on alpha-glucosidase was competitive inhibition. GF-H
      was as good as acarbose in inhibiting the starch digestion in vitro. Oleic acid
      and linoleic acid could be the major active constituents that have contributed to
      the potency of GF in inhibiting alpha-glucosidase activity. 

PMID- 24033598
TI  - Derivation of the extrinsic values of biological diversity from its intrinsic
      value and of both from the first principles of evolution.
AB  - Conservation ethics have been based on 2 philosophical value systems: extrinsic
      value (defined broadly to include all values that derive from something external
      to the thing valued) and intrinsic value. Valuing biological diversity on the
      basis of an extrinsic value system is problematic because measurement is often
      difficult; extrinsic value changes as spatial or temporal scales change;
      extrinsic value differs on the basis of external factors; some species have
      trivial or negative extrinsic values; and extrinsic value varies across human
      cultures and societies and with such factors as socioeconomic conditions,
      individual experiences, and educational backgrounds. Valuing biological diversity
      on the basis of an intrinsic value system also poses challenges because intrinsic
      value can be seen as a disguised form of human extrinsic value; intrinsic value
      is initially ambiguous as to which objects or characteristics of biological
      diversity are to being valued; all aspects of biological diversity (e.g., species
      and ecosystems) are transitory; species and ecosystems are not static concrete
      entities; and intrinsic value of one species is often in conflict with the
      intrinsic value of other species. Extrinsic and intrinsic value systems share a
      common origin, such that extrinsic values are always derived from intrinsic value
      and life mutely expresses both intrinsic and extrinsic values-these are derived
      from and are products of biological evolution. Probing the values that underlie
      conservation helps the community clearly articulate its aims. Derivacion de los
      Valores Extrinsecos de la Biodiversidad a Partir de sus Valores Intrinsecos y de
      Ambos a Partir de los Primeros Principios de la Evolucion. 

PMID- 24033599
TI  - Organ donation: what else can be done besides legislature?
AB  - With the ongoing organ shortage for transplantation, Singapore has adopted an
      organ opt-out scheme: Human Organ Transplant Act (HOTA) that presumes consent
      unless specified otherwise. Likewise, receptivity of doctors and medical students
      (MS), as future doctors, can positively influence organ donation (OD) rates. We
      explored the knowledge and attitudes of MS toward OD. MS from all five yr of
      medical school were recruited using self-administered questionnaires. There were
      294 completed questionnaires with 49.3% males and 45.6% pre-clinical students.
      The MS were generally knowledgeable about organ transplantation, but deficient in
      the knowledge of some aspects of HOTA. The majority of the MS were receptive
      toward OD. Traditional values rather than religion were possible barriers toward
      OD. 50.7% of the MS were concerned that donated organs may be inappropriately
      used, while 32% had concerns that doctors would prematurely terminate treatment
      if the patient is a potential organ donor. Fewer clinical students shared such
      concerns, compared with the pre-clinical students. The MS have a good
      understanding of basic tenets of OD and are receptive toward OD. Potential
      barriers for OD advocation are local traditional values and reservations
      regarding the appropriate use of harvested organs and provision of appropriate
      care to donor patients. These concerns are areas to address. 

PMID- 24033600
TI  - Different methods of hilar clamping during partial nephrectomy: Impact on renal
      function.
AB  - OBJECTIVES: To evaluate the impact of different hilar clamping methods on changes
      in renal function after partial nephrectomy. METHODS: We analyzed the clinical
      data of 369 patients who underwent partial nephrectomy for a single renal tumor
      of size <=4.0 cm and a normal contralateral kidney. Patients were separated into
      three groups depending on hilar clamping method: non-clamping, cold ischemia and
      warm ischemia. Estimated glomerular filtration rate was examined at preoperative,
      nadir and 1 year postoperatively. Percent change in estimated glomerular
      filtration rate was used as the parameter to assess the renal functional outcome.
      RESULTS: Percent change in nadir estimated glomerular filtration rate in the non
      clamping group was significantly less compared with the cold ischemia and warm
      ischemia groups (P < 0.001). However, no significant differences among the groups
      were noted in percent change of estimated glomerular filtration rate at 1 year (P
      = 0.348). The cold ischemia group had a similar serial change of postoperative
      renal function compared with the warm ischemia group. Percent change in 1-year
      estimated glomerular filtration rate increased with increasing ischemia time in
      the cold ischemia (P for trend = 0.073) and warm ischemia groups (P for trend =
      0.010). On multivariate analysis, hilar clamping (both warm ischemia and cold
      ischemia) were significantly associated with percent change in nadir estimated
      glomerular filtration rate, but not in 1-year estimated glomerular filtration
      rate. CONCLUSIONS: Non-clamping partial nephrectomy results in a lower percent
      change in nadir estimated glomerular filtration rate, whereas it carries an
      estimated glomerular filtration rate change at 1 year that is similar to partial
      nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia
      provide a similar effect on renal function. Therefore, when hilar clamping is
      required, minimization of ischemia time is necessary.

PMID- 24033601
TI  - Comparison of continuous-flow and pulsatile-flow blood pumps on reducing
      pulmonary artery pressure in patients with fixed pulmonary hypertension.
AB  - Pulmonary hypertension (PH) is considered as a risk factor for morbidity and
      mortality in patients undergoing heart transplantation. Recently, left
      ventricular assist device (LVAD) implantation has been increasingly used in
      reducing pulmonary artery pressure (PAP) in patients with PH unresponsive to
      medical therapy. Herein, we aimed to compare the efficacy of continuous-flow and
      pulsatile-flow blood pumps on the improvement of PH in mechanical circulatory
      support patients. Twenty-seven patients with end-stage heart failure who
      underwent LVAD implantation surgery were enrolled. Fifteen of them (55.6%) had
      continuous-flow pump (HeartWare Ventricular Assist System, HeartWare, Inc.,
      Miramar, FL, USA), and 12 of them (44.4%) had pulsatile pump (Berlin Heart EXCOR
      ventricular assist device, Berlin Heart AG, Berlin, Germany). The efficacy of
      LVADs on the improvement of PH was compared between continuous-flow and pulsatile
      pumps by the evaluation of systolic PAP, tricuspid annular plane systolic
      excursion (TAPSE), right ventricular systolic motion (RVSM), right ventricular
      ejection fraction (RVEF), and grade of tricuspid insufficiency (TI) for each of
      the study participants. All of the 15 patients who underwent continuous-flow
      blood pump implantation surgery (Group 1) were male with a mean age of 46.9 +/-
      11.7 years, and in pulsatile-flow blood pump implanted participants (Group 2),
      the mean age was 40.6 +/- 16.8 years, all of whom were also male (P=0.259). Mean
      follow-up was 313.7 +/- 241.3 days in Group 1 and 448.7 +/- 120.7 days in Group 2
      (P=0.139). In Group 1, mean preoperative and postoperative systolic PAP were
      measured as 51.7 +/- 12.2 mm Hg and 22.2 +/- 3.4 mm Hg, respectively, while those
      in Group 2 were 54.5 +/- 7.5 mm Hg and 33.9 +/- 6.4 mm Hg, respectively. A
      significantly greater decrease in systolic PAP was noticed in patients with
      continuous-flow blood pumps (P=0.023); however, no statistically significant
      difference was found when we considered the change in TAPSE between study groups
      (P=0.112). A statistical significance in the alteration of RVEF, RVSM, and the
      grade of TI during study visits was not found between the study groups (P=0.472,
      P=0.887, and P=0.237, respectively). Although the two studied types of LVADs were
      found to be effective in reducing PAP in heart transplantation candidates with
      PH, lesser postoperative systolic PAP values were achieved in patients who
      underwent continuous-flow pump implantation surgery.

PMID- 24033602
TI  - Ophthalmological outcome and visuospatial ability in very preterm children
      measured at 2.5 years corrected age.
AB  - AIM: To investigate the ophthalmological outcome of very preterm children at 2.5
      years corrected age (CA) and perform a test of visuospatial and cognitive
      abilities. METHODS: A population-based, prospective study (LOVIS study) in
      Uppsala County, Sweden, comprised 111 very preterm children (<32 w gestational
      age [GA]) born between 1 January 2004 and 31 December 2007. Ophthalmic
      evaluations were undertaken in 98/109 children (89.9%) alive at 2.5 years.
      Spatial cognition was investigated with a test of five alternative blocks in 48
      preterm and 25 term-born children. RESULTS: Visual impairment, strabismus or
      refractive errors, were found in 12% of the children. None of the children were
      blind in both eyes. Logistic regression analyses revealed significant
      associations between strabismus and periventricular leucomalacia/intraventricular
      haemorrhage (OR 9.6, p = 0.025) and between refractive errors and severe
      retinopathy of prematurity (OR 9.8, p = 0.011) and GA (OR 0.763, p = 0.034). Oval
      and rectangular blocks were significantly more difficult to insert into a box for
      preterm than full-term children (p = 0.048 and 0.013, respectively). There was a
      significant correlation between total scores for the five blocks and GA at birth
      (p = 0.035). CONCLUSION: Eye and visual problems were found in 12% of the preterm
      children at 30 months CA. Preterm children had difficulties with blocks of
      complex shapes.

PMID- 24033603
TI  - The impact of exposure to peer suicidal self-directed violence on youth suicidal
      behavior: a critical review of the literature.
AB  - There is considerable evidence that being exposed to the suicide or suicidal
      behavior of another can increase the risk for suicide. Significant relationships
      between media coverage and youth suicide have been documented in the professional
      literature. Exposure to familial suicidal behavior has also been established as a
      risk factor for youth suicidal behavior; However, peer suicide exposure is not as
      clear cut as research results in this area have been mixed. In the current paper
      the empirical literature focused on the associations between exposure to peer
      suicides and suicide attempts and youth suicidal behavior is critically reviewed.
      Effect sizes were computed for each of the 23 studies included in the review to
      allow for cross-study comparisons. The results demonstrate that having a friend
      or acquaintance attempt suicide is significantly related to risk for suicidal
      thoughts and behavior. However, the support for the relationship between the
      suicide of a peer and youth suicidal behavior was less consistent. Implications
      for clinical practice and suicide postvention as well as areas of future research
      are discussed. 

PMID- 24033604
TI  - Tolerogenic CX3CR1+ B cells suppress food allergy-induced intestinal inflammation
      in mice.
AB  - BACKGROUND: B lymphocytes are an important cell population of the immune
      regulation; their role in the regulation of food allergy has not been fully
      understood yet. OBJECTIVE: This study aims to investigate the role of a
      subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T
      cells (Treg) and in the suppression of food allergy-induced intestinal
      inflammation in mice. METHODS: The intestinal mucosa-derived CD5+ CD19+ CX3CR1+
      TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper
      (Th)2 inflammation was established to assess the immune regulatory role of this
      subpopulation of TolBCs. RESULTS: A subpopulation of CD5+ CD19+ CX3CR1+ B cells
      was detected in the mouse intestinal mucosa. The cells also expressed
      transforming growth factor (TGF)-beta and carried integrin alpha v beta 6
      (alphavbeta6). Exposure to recombinant alphavbeta6 and anti-IgM antibody induced
      naive B cells to differentiate into the TGF-beta-producing TolBCs. Coculturing
      this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs.
      Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced
      intestinal Th2 pattern inflammation in mice. CONCLUSIONS: CD5+ CD19+ CX3CR1+
      TolBCs are capable of inducing Tregs in the intestine and suppress food allergy
      related Th2 pattern inflammation in mice.

PMID- 24033605
TI  - Tumor-suppressive microRNA-143/145 cluster targets hexokinase-2 in renal cell
      carcinoma.
AB  - Our recent studies of microRNA (miRNA) expression signatures have indicated that
      the miR-143/145 cluster is significantly downregulated in several types of cancer
      and represents a putative tumor-suppressive miRNA in human cancers. The aim of
      this study was to investigate the functional significance of the miR-143/145
      cluster in cancer cells and to identify novel molecular targets of the miR
      143/145 cluster in renal cell carcinoma (RCC). The expression levels of miR-143
      and miR-145 were significantly downregulated in RCC tissues compared with
      adjacent non-cancerous tissues. A significant positive correlation was recognized
      between miR-143 and miR-145 expression. Restoration of mature miR-143 or miR-145
      in 786-O and A498 RCC cells revealed that both mature miRNAs significantly
      inhibited cancer cell proliferation and invasion, suggesting that the miR-143/145
      cluster functioned as a tumor suppressor in RCC. Gene expression data and in
      silico database analysis showed that the hexokinase-2 (HK2) gene, which encodes a
      glycolytic enzyme crucial for the Warburg effect in cancer cells, was a candidate
      target of the miR-143/145 cluster. Luciferase reporter assays showed that both
      miR-143 and miR-145 directly regulated HK2. In RCC clinical specimens, the
      expression of HK2 was significantly higher in cancer tissues than in non
      cancerous tissues. Silencing HK2 suppressed RCC cell proliferation and invasion,
      suggesting that HK2 has oncogenic functions in RCC. Thus, our data showed that
      loss of the tumor-suppressive miR-143/145 cluster enhanced RCC cell proliferation
      and invasion through targeting HK2. 

PMID- 24033606
TI  - Adrenal ganglioneuroma: features and outcomes of 27 cases at a referral cancer
      centre.
AB  - BACKGROUND: Adrenal ganglioneuroma (AGN) is a rare neurogenic tumour that can
      mimic other adrenal neoplasms. Limited information, mostly derived from small
      cases series, is available for AGN. METHODS: A retrospective review for AGNs seen
      at a tertiary referral centre describing important features to distinguish AGN
      from other adrenal neoplasms. RESULTS: Of 53 ganglioneuromas, 27 were AGNs.
      Median age was 31 years (range, 1.7-64 years) and median tumour size was 8 cm
      (range, 1.5-20 cm). Seventeen AGNs (63%) were detected incidentally and nine
      patients (33%) presented with abdominal/back discomfort. Catecholamine levels,
      available for 21 patients, were normal. On computed tomography (CT), most AGNs
      were homogenous and well circumscribed with a median density of 32.5 Hounsfield
      units (HU) on unenhanced CT; 40 HU on postcontrast venous phase; and 66.5 HU on
      delayed postcontrast phase. On magnetic resonance imaging (MRI), AGNs had hypo
      intense signal on T1-weighted images with heterogeneous hyperintense signal on T2
      weighted images. In four patients, there was no tumour growth during median
      follow-up of 48 months (range, 21-60 months). One patient had malignant
      peripheral nerve sheath tumour arising from AGN. Thirteen patients with resected
      AGN had no recurrence during a median follow-up of 50 months (range, 2-135
      months). CONCLUSIONS: We herein describe the largest AGN series reported to date.
      Isolated AGNs do not produce catecholamines and have CT imaging characteristics
      that can help in distinguishing them from other adrenal and para-adrenal
      neoplasms. The natural history of AGNs is usually benign, although local extra
      adrenal extension or malignant transformation can rarely occur.

PMID- 24033607
TI  - Rearing conditions influence nutrient availability of plant extracts supplemented
      diets when fed to broiler chickens.
AB  - The effects of a standardised mixture of essential oils, including 5% carvacrol,
      3% cinnamaldehyde and 2% capsicum (XT 6930; Pancosma S.A), on dietary apparent
      metabolisable energy corrected for nitrogen retention (AMEn), nutrient
      digestibility and mucin secretions, measured as sialic acid (SA) were
      investigated in broilers fed on the same diet but reared under different
      conditions, that is, cages and floor pens littered with wood shavings used in
      previous broiler study. The use of XT reduced (p < 0.05) nitrogen digestibility
      (0.585 vs. 0.544) and tended (p = 0.072) to reduce dry matter digestibility
      (0.733 vs. 0.717) of the diet when fed to birds reared in cages. However, XT
      supplementation improved (p < 0.05) fat digestibility (0.844 vs. 0.862) and
      tended (p = 0.093) to increase AMEn (14.01 vs. 14.25 MJ/kg DM) of the same diet
      when fed to broilers reared in floor pens. Essential oils supplementation tended
      (p = 0.059) to increase the secretion of SA, when fed to birds reared in cages
      (11.24 vs. 14.18 MUg), but did not influence (p > 0.05) the SA secretion from
      birds reared in floor pens. The results obtained from the cage study tend to be
      the opposite of those obtained from the floor pen study. This suggests that the
      efficiency of dietary plant extracts may be influenced by the rearing/hygienic
      conditions of poultry. Based on the overall results, it can be concluded that
      information on rearing conditions should be taken into account for more complete
      interpretation of the experimental data emanating from experiments involving use
      of essential oils typified by those considered in this study. 

PMID- 24033608
TI  - Treg cells are negatively correlated with increased memory B cells in pre
      eclampsia while maintaining suppressive function on autologous B-cell
      proliferation.
AB  - PROBLEM: The objective of this study was to determine the simultaneous changes
      and the correlation between circulating regulatory T (Tregs) and B-cell subsets
      in normal pregnancy (NP) and pre-eclampsia (PE). Meanwhile, the regulatory
      function of Tregs on B-cell proliferation was evaluated in vitro. METHOD OF
      STUDY: A total of 32 PE and 40 NP women matched for age, gestational age, and
      parity were included. Using flow cytometry, the percentages of peripheral blood
      Tregs and B-cell subsets were determined. Moreover, the regulatory function of
      Tregs on autologous B-cell proliferation in PE and NP was investigated in vitro
      by flow cytometry and analyzed by modfit software. RESULTS: The proportions (%)
      of CD4(+)  Foxp3(+) (P < 0.001) and CD4(+)  CD25(+)  Foxp3(+) (P < 0.01) cells
      within total CD4(+) T cells were significantly decreased in PE as compared to
      those of NP. However, no difference was found in CD4(+)  CD25(+) cells in CD4(+)
      T cell population. CD19(+)  CD27(+) (P < 0.05) and CD19(+)  CD27(+)  IgD(+) (P <
      0.01) B cells within CD19(+) B cells (%) in PE were higher than those of NP.
      Negative correlations between the percentage of CD4(+)  CD25(+)  Foxp3(+) in
      CD4(+) T cells and that of CD19(+)  CD27(+) (r = -0.384, P < 0.05) and CD19(+) 
      CD27(+)  IgD(+) (r = -0.402, P < 0.05) in CD19(+) B cells were present in PE but
      not in NP. Furthermore, the in vitro study demonstrated a significant increase in
      B-cell proliferation in PE as compared to NP. Tregs in PE were able to suppress
      the proliferation and precursor frequency of autologous B cells (P < 0.05 each).
      CONCLUSION: The study indicates that a negative correlation between Tregs and
      memory B cells is present in women with PE, characterized by a systemic decrease
      in Tregs and an increase in memory B cells. Although the quantitative deficit of
      Tregs is present in PE, the Tregs still have a suppressive role in autologous B
      cell proliferation.

PMID- 24033609
TI  - Can individual patients assess differences in quality of life between groups of
      patients?
AB  - This qualitative study piloted a method for eliciting patient opinion on the size
      of group differences in quality of life (QOL) scores from the EORTC QLQ-C30.
      Using scenarios from published studies, patients were asked the differences in
      QOL they would expect between two groups of patients or a group of patients over
      time. Interviews were transcribed verbatim and thematic analysis used. Eleven
      breast cancer patients were interviewed. The final thematic framework consisted
      of three major themes: (1) their ability to use published data to judge the size
      of differences in QOL scores, (2) their ability to gain familiarity and
      understanding of the QLQ-C30 questionnaire in an interview situation and (3)
      their ability to understand and assess differences from a group of patients
      rather than on an individual basis. Patients felt able to understand the
      questionnaire and scoring. They provided an opinion on whether differences in QOL
      scores were trivial, small, medium or large. Patient perspectives were often
      based on their own experience of the disease and treatments and their opinions
      were varied. In order to estimate clinically meaningful differences from
      published literature, a larger number of patients with varied experiences would
      be required and a consensus process used to align opinions where possible. 

PMID- 24033610
TI  - The role of SDF-1 and CXCR4 on odontoblastic differentiation in human dental pulp
      cells.
AB  - AIM: To examine the role of stromal cell-derived factor 1 (SDF-1) signalling
      during odontogenic differentiation in human dental pulp cells (HDPCs).
      METHODOLOGY: Human dental pulp cells were treated with differentiation medium,
      recombinant human SDF-1, neutralizing antibody for SDF-1 or CXCR4, pertussis
      toxin (PTX) and AMD3100. The expression of SDF-1 and its receptor chemokine
      receptor type 4 (CXCR4) was measured by reverse transcription-polymerase chain
      reaction (RT-PCR) and Western blotting. Odontoblastic differentiation was
      determined using alkaline phosphatase (ALP) activity assay, mineralized nodule
      formation and marker mRNAs by RT-PCR. RESULTS: Marked upregulation of SDF-1 and
      CXCR4 mRNA and protein was observed in cells grown 7 days in osteogenic induction
      medium. The addition of recombinant human SDF-1 to HDPCs significantly (P < 0.05)
      increased ALP activity, mineralized nodule formation and odontoblast marker mRNAs
      in a dose-dependent manner. Blocking SDF-1 signalling using antibodies against
      SDF-1 or CXCR4, or the G-protein-coupled receptor inhibitor PTX, and CXCR4
      inhibitor AMD3100, strongly suppressed induction of odontogenic differentiation
      in HDPCs. CONCLUSIONS: Odontoblastic differentiation was stimulated by SDF-1
      activation and repressed by SDF-1/CXCR4 inhibition. Thus, SDF-1/CXCR4 signalling
      may be a new therapeutic target and strategy to promote repair and regeneration
      in endodontics.

PMID- 24033611
TI  - Effects of stair-climbing on balance, gait, strength, resting heart rate, and
      submaximal endurance in healthy seniors.
AB  - Stair-climbing serves as a feasible opportunity to remain physically active
      within everyday-life. Data on neuromuscular and cardiorespiratory performance
      after regular stair-climbing in seniors are scarce. Forty-eight seniors were
      stratified to a one- (taking every step, INT1) or two-step strategy (every second
      step, INT2) or a control group (CON). Thirty-nine seniors [females: n = 22,
      males: n = 17; age: 70.5 (SD 5.1) years; BMI: 25.8 (3.1) kg/m(2)] completed the 8
      week intervention (three weekly sessions). Before and after the intervention,
      balance, gait, strength, and submaximal endurance (at different intensities) were
      assessed. Maximal strength and explosive power did not improve significantly
      (0.10 < P < 0.78). Resting heart rate was significantly reduced in INT2 (-8/min)
      compared with INT1 (0/min, P = 0.02) and CON (0/min, P = 0.03). Compared with
      CON, perceived exertion for all intensities (0.007 < P < 0.03) and submaximal
      exercise heart rate during moderate uphill walking significantly decreased (
      11/min; P < 0.05) in INT2. Step counts for forward beam balancing (4.5 cm width)
      increased in INT2 (P = 0.007) compared with CON. With more pronounced effects in
      INT2, stair-climbing significantly improved resting and exercise heart rates,
      perceived exertion, and dynamic balance performance in healthy seniors and may
      contribute to better overall fitness, reduced fall risk, and less perceived
      strain during daily life activities.

PMID- 24033612
TI  - Society of cosmetic scientists - birthday greetings!

PMID- 24033613
TI  - Relationship between vitamin D knowledge and 25-hydroxyvitamin D levels amongst
      pregnant women.
AB  - BACKGROUND: Pregnant women living at northerly latitudes are at risk of
      suboptimal vitamin D status. There is a paucity of studies correlating knowledge,
      attitudes and practices of vitamin D with serum levels amongst pregnant women. We
      aimed to determine the prevalence of suboptimal vitamin D status in pregnant
      women of various ethnicities attending two Dublin maternity hospitals and to
      assess levels of knowledge, attitudes and practices concerning vitamin D.
      METHODS: We conducted a cross-sectional study of 116 pregnant women of Irish,
      Asian, Sub-Saharan African and Middle Eastern and North African (MENA) origin.
      Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D
      (25OHD). We examined knowledge, attitudes and practices concerning vitamin D
      using an interview-assisted questionnaire. RESULTS: The median (interquartile
      range) 25OHD level was 25.9 (16.5-44.7) nmol L(-1). Using a cut-off point of <30
      nmol L(-1) , the proportion at risk of deficiency was significantly higher among
      MENA (88%; P < 0.001) and Sub-Saharan African women (68%; P = 0.019) than Irish
      women (36%). Eighty-two women (71%) reported they had insufficient knowledge
      about vitamin D and its sources. Vitamin D containing supplement usage was the
      strongest predictor of 25OHD levels >=30 nmol L(-1) (odds ratio = 18.03, 95%
      confidence interval = 5.7256.8, P < 0.001). CONCLUSIONS: Suboptimal vitamin D
      status is common in this cohort of pregnant women, especially among those of Sub
      Saharan African and MENA origin. Awareness of vitamin D dietary sources is poor
      among all subgroups. Recommending vitamin D containing supplements may be the
      best strategy at present for improving vitamin D status with a need for increased
      vitamin D education.

PMID- 24033615
TI  - An evaluation of the pharmacokinetics of treprostinil diolamine in subjects with
      hepatic impairment.
AB  - WHAT IS KNOWN AND OBJECTIVE: Treprostinil diolamine (oral treprostinil) is a
      prostacyclin analogue under evaluation for the treatment for pulmonary arterial
      hypertension (PAH). This study assessed the pharmacokinetics (PK) and safety of
      treprostinil following oral administration of a single sustained-release 1 mg
      dose in subjects with hepatic impairment. METHODS: Four cohorts, including
      healthy volunteers, and subjects with mild, moderate and severe hepatic
      impairment were enrolled. Thirty subjects completed the study. Mean treprostinil
      clearance values (CL/F) decreased with the severity of hepatic impairment. The
      decrease in CL/F resulted in a marked increase in exposure levels of
      treprostinil. Relative to healthy subjects, mean area under the curve from time
      zero to 24 h after dosing interval (AUC0-24) values in subjects with mild,
      moderate and severe hepatic impairment increased by approximately 2.2-, 4.9- and
      7.6-fold, respectively. The most frequent adverse events (AEs) exhibited in this
      study were similar to those seen with prostacyclin and its analogues and with AEs
      seen in other clinical studies with oral treprostinil (e.g. headache, diarrhoea
      and nausea). The overall incidence of all AEs and the specific events of headache
      and nausea increased with severity of hepatic impairment. WHAT IS NEW AND
      CONCLUSION: Based on these results, dosage adjustments should be performed in
      subjects with hepatic impairment.

PMID- 24033614
TI  - Treatment options in painful chronic pancreatitis: a systematic review.
AB  - BACKGROUND: Longlasting and unbearable pain is the most common and striking
      symptom of chronic pancreatitis. Accordingly, pain relief and improvement in
      patients' quality of life are the primary goals in the treatment of this disease.
      This systematic review aims to summarize the available data on treatment options.
      METHODS: A systematic search of MEDLINE/PubMed and the Cochrane Library was
      performed according to the PRISMA statement for reporting systematic reviews and
      meta-analysis. The search was limited to randomized controlled trials and meta
      analyses. Reference lists were then hand-searched for additional relevant titles.
      The results obtained were examined individually by two independent investigators
      for further selection and data extraction. RESULTS: A total of 416 abstracts were
      reviewed, of which 367 were excluded because they were obviously irrelevant or
      represented overlapping studies. Consequently, 49 full-text articles were
      systematically reviewed. CONCLUSIONS: First-line medical options include the
      provision of pain medication, adjunctive agents and pancreatic enzymes, and
      abstinence from alcohol and tobacco. If medical treatment fails, endoscopic
      treatment offers pain relief in the majority of patients in the short term.
      However, current data suggest that surgical treatment seems to be superior to
      endoscopic intervention because it is significantly more effective and,
      especially, lasts longer.

PMID- 24033616
TI  - Using genetic techniques to quantify reinvasion, survival and in situ breeding
      rates during control operations.
AB  - Determining the origin of individuals caught during a control/eradication
      programme enables conservation managers to assess the reinvasion rates of their
      target species and evaluate the level of success of their control methods. We
      examine how genetic techniques can focus management by distinguishing between
      hypotheses of 'reinvasion' and 'survivor', and defining kin groups for invasive
      stoats (Mustela erminea) on Secretary Island, New Zealand. 205 stoats caught on
      the island were genotyped at 16 microsatellite loci, along with 40 stoats from
      the opposing mainland coast, and the age and sex were determined for each
      individual. Using these data, we compare and combine a variety of genetic
      techniques including genetic clustering, population assignment and kinship-based
      techniques to assess the origin of each stoat. The population history and
      individual movement could be described in fine detail, with results indicating
      that both in-situ survival and breeding, and reinvasion are occurring.
      Immigration to the island was found to be generally low, apart from in 1 year
      where around 8 stoats emigrated from the mainland. This increased immigration was
      probably linked to a stoat population spike on the mainland in that year, caused
      by a masting event of southern beech forest (Nothofagus sp.) and the subsequent
      rodent irruption. Our study provides an example of some of the ways genetic
      analyses can feed directly into informing management practices for invasive
      species.

PMID- 24033617
TI  - Traumatic intracranial injury in intoxicated patients with minor head trauma.
AB  - OBJECTIVES: Studies focusing on minor head injury in intoxicated patients report
      disparate prevalences of intracranial injury. It is unclear if the typical
      factors associated with intracranial injury in published clinical decision rules
      for computerized tomography (CT) acquisition are helpful in differentiating
      patients with and without intracranial injuries, as intoxication may obscure
      particular features of intracranial injury such as headache and mimic other signs
      of head injury such as altered mental status. This study aimed to estimate the
      prevalence of intracranial injury following minor head injury (Glasgow Coma Scale
      [GCS] score >=14) in intoxicated patients and to assess the performance of
      established clinical decision rules in this population. METHODS: This was a
      prospective cohort study of consecutive intoxicated adults presenting to the
      emergency department (ED) following minor head injury. Historical and physical
      examination features included those from the Canadian CT Head Rule, National
      Emergency X-Radiography Utilization Study (NEXUS), and New Orleans Criteria. All
      patients underwent head CT. RESULTS: A total of 283 patients were enrolled, with
      a median age of 40 years (interquartile range [IQR] = 28 to 48 years) and median
      alcohol concentration of 195 mmol/L (IQR = 154 to 256 mmol/L). A total of 238 of
      283 (84%) were male, and 225 (80%) had GCS scores of 15. Clinically important
      injuries (injuries requiring admission to the hospital or neurosurgical follow
      up) were identified in 23 patients (8%; 95% confidence interval [CI] = 5% to
      12%); one required neurosurgical intervention (0.4%, 95% CI = 0% to 2%). Loss of
      consciousness and headache were associated with clinically important intracranial
      injury on CT. The Canadian CT Head Rule had a sensitivity of 70% (95% CI = 47% to
      87%) and NEXUS criteria had a sensitivity of 83% (95% CI = 61% to 95%) for
      clinically important injury in intoxicated patients. CONCLUSIONS: In this study,
      the prevalence of clinically important injury in intoxicated patients with minor
      head injury was significant. While the presence of the common features associated
      with intracranial injury in nonintoxicated patients should raise clinical
      suspicion for intracranial injury in intoxicated patients, the Canadian CT Head
      Rule and NEXUS criteria do not have adequate sensitivity to be applied in
      intoxicated patients with minor head injury.

PMID- 24033618
TI  - Provision of out-of-hospital analgesia to older fallers with suspected fractures:
      above par, but opportunities for improvement exist.
AB  - OBJECTIVES: Paramedics frequently attend older patients who have fallen and
      sustained suspected fractures, a population of patients who may be at risk of
      inadequate analgesic care. This prospective study aimed to describe the rate and
      effectiveness of analgesia administered by paramedics to older patients with
      suspected fractures secondary to falls and to identify predictive factors
      associated with provision of analgesia. METHODS: A cohort of older patients aged
      greater than 65 years with suspected fall-related fractures was extracted from a
      database of 1,610 cases collected during a prospective, nonconsecutive
      observational study of older people who had fallen and received an ambulance
      response from October 1, 2010, through June 30, 2011. Fall-specific data,
      collected on scene by paramedics using a specially designed data form, were
      linked to patient clinical records and dispatch information. Descriptive analyses
      were performed to describe rates and effectiveness of analgesic administration,
      and multivariate logistic regression was conducted to identify factors associated
      with provision of analgesia. RESULTS: Of 1,610 patients in the observational
      study database, there were 333 patients identified as having suspected fractures,
      thus forming the study population. The mean (+/-SD) age was 82 (+/-8) years, and
      75% were female. Suspected fractures of the hip were most common (42%). An
      initial pain score was recorded in 67% of cases, and the median initial pain
      severity was 8 of 10 (interquartile range [IQR] = 5 to 9). Overall, 60% received
      analgesia, and 80% of those received parenteral opiates. Intravenous (IV)
      morphine was most common (63%), followed by methoxyflurane (39%) and intranasal
      fentanyl (17%). Administration of oral analgesics was uncommon. Analgesia was
      considered to be clinically effective (>=30% relative reduction in pain severity)
      in 62% of cases. Patients with suspected hip fractures had greater odds of
      receiving analgesia compared to those with suspected fractures at other
      anatomical sites (odds ratio [OR] = 2.7, 95% confidence interval [CI] = 1.17 to
      6.32; p = 0.02). Compared to those with mild pain, the odds of receiving
      analgesia increased significantly for patients with moderate pain (OR = 6.5, 95%
      CI = 2.3 to 18.8; p < 0.0001) and severe pain (OR = 31.1, 95% CI = 9.9 to 97.6; p
      < 0.0001). CONCLUSIONS: In this population of older people who fell and sustained
      suspected fractures, two-thirds received paramedic-administered analgesia. The
      majority of patients received clinically effective analgesia, and the presence of
      a suspected hip fracture increased the likelihood of receiving pain relief.

PMID- 24033619
TI  - Forecasting daily emergency department visits using calendar variables and
      ambient temperature readings.
AB  - OBJECTIVES: This study aimed to develop different models to forecast the daily
      number of patients seeking emergency department (ED) care in a general hospital
      according to calendar variables and ambient temperature readings and to compare
      the models in terms of forecasting accuracy. METHODS: The authors developed and
      tested six different models of ED patient visits using total daily counts of
      patient visits to an ED in Sao Paulo, Brazil, from January 1, 2008, to December
      31, 2010. The first 33 months of the data set were used to develop the ED patient
      visits forecasting models (the training set), leaving the last 3 months to
      measure each model's forecasting accuracy by the mean absolute percentage error
      (MAPE). Forecasting models were developed using three different time-series
      analysis methods: generalized linear models (GLM), generalized estimating
      equations (GEE), and seasonal autoregressive integrated moving average (SARIMA).
      For each method, models were explored with and without the effect of mean daily
      temperature as a predictive variable. RESULTS: The daily mean number of ED visits
      was 389, ranging from 166 to 613. Data showed a weekly seasonal distribution,
      with highest patient volumes on Mondays and lowest patient volumes on weekends.
      There was little variation in daily visits by month. GLM and GEE models showed
      better forecasting accuracy than SARIMA models. For instance, the MAPEs from GLM
      models and GEE models at the first month of forecasting (October 2012) were 11.5
      and 10.8% (models with and without control for the temperature effect,
      respectively), while the MAPEs from SARIMA models were 12.8 and 11.7%. For all
      models, controlling for the effect of temperature resulted in worse or similar
      forecasting ability than models with calendar variables alone, and forecasting
      accuracy was better for the short-term horizon (7 days in advance) than for the
      longer term (30 days in advance). CONCLUSIONS: This study indicates that time
      series models can be developed to provide forecasts of daily ED patient visits,
      and forecasting ability was dependent on the type of model employed and the
      length of the time horizon being predicted. In this setting, GLM and GEE models
      showed better accuracy than SARIMA models. Including information about ambient
      temperature in the models did not improve forecasting accuracy. Forecasting
      models based on calendar variables alone did in general detect patterns of daily
      variability in ED volume and thus could be used for developing an automated
      system for better planning of personnel resources.

PMID- 24033620
TI  - Qualitative factors in patients who die shortly after emergency department
      discharge.
AB  - OBJECTIVES: Early death after emergency department (ED) discharge may signal
      opportunities to improve care. Prior studies are limited by incomplete mortality
      ascertainment and lack of clinically important information in administrative
      data. The goal in this hypothesis-generating study was to identify patient and
      process of care themes that may provide possible explanations for early
      postdischarge mortality. METHODS: This was a qualitative analysis of medical
      records of adult patients who visited the ED of any of six hospitals in an
      integrated health system (Kaiser Permanente Southern California [KPSC]) and died
      within 7 days of discharge in 2007 and 2008. Nonmembers, visits to non-health
      plan hospitals, patients receiving or referred to hospice care, and patients with
      do not attempt resuscitation or do not intubate orders (DNAR/DNI) were excluded.
      Under the guidance of two qualitative research scientists, a team of three
      emergency physicians used grounded theory techniques to identify patient clinical
      presentations and processes of care that serve as potential explanations for poor
      outcome after discharge. RESULTS: The source population consisted of a total of
      290,092 members with 446,120 discharges from six KPSC EDs in 2007 and 2008. A
      total of 203 deaths occurred within 7 days of ED discharge (0.05%). Sixty-one
      randomly chosen cases were reviewed. Patient-level themes that emerged included
      an unexplained persistent acute change in mental status, recent fall, abnormal
      vital signs, ill-appearing presentation, malfunctioning indwelling device, and
      presenting symptoms remaining at discharge. Process-of-care factors included a
      discrepancy in history of present illness, incomplete physical examination, and
      change of discharge plan by a third party, such as a consulting or admitting
      physician. CONCLUSIONS: In this hypothesis-generating study, qualitative research
      techniques were used to identify clinical and process-of-care factors in patients
      who died within days after discharge from an ED. These potential predictors will
      be formally tested in a future quantitative study.

PMID- 24033621
TI  - Influenza testing, diagnosis, and treatment in the emergency department in 2009
      2010 and 2010-2011.
AB  - OBJECTIVES: The objective was to describe patterns of rapid influenza test
      ordering, diagnosis of influenza, and antiviral prescribing by the treating
      physician for children and adults presenting to emergency departments (EDs) with
      fever and acute respiratory symptoms in Winston-Salem, North Carolina, over two
      influenza seasons. METHODS: The authors prospectively enrolled patients
      presenting to the ED with fever and acute respiratory symptoms for two influenza
      seasons: H1N1 pandemic of September 2009 through mid-May 2010 and November 2010
      through April 2011. Enrolled patients had nose or and throat swabs obtained and
      tested for influenza by viral culture and polymerase chain reaction (PCR)
      testing. Demographic information and medical history were obtained by patient or
      guardian report. Testing, treatment, and discharge diagnosis from the ED visit,
      as well as medical history and insurance status, were ascertained from chart
      review. RESULTS: Among 2,293 eligible patients approached, 1,657 (72%) were
      enrolled, of whom 38% were younger than 18 years, 47% were 18 to 49 years, and
      15% were 50 years of age and older. Overall, 14% had culture- or PCR-confirmed
      influenza. The odds of 1) rapid influenza test ordering, 2) a physician diagnosis
      of influenza, and 3) prescribing antiviral treatment during the ED visit were
      fourfold higher among patients with than without culture- or PCR-confirmed
      influenza. The odds of rapid influenza test ordering were threefold lower in
      2009/2010 than 2010/2011, whereas the odds of physician diagnosis of influenza
      and antiviral prescriptions were 2- and 3.5-fold higher, respectively.
      CONCLUSIONS: In 2009/2010 compared to 2010/2011, the odds of rapid influenza test
      ordering were lower, whereas the odds of influenza-specific discharge diagnoses
      and antiviral prescriptions were higher among patients presenting to the ED with
      culture/PCR-confirmed influenza. These results demonstrated a gap between
      clinical practice and recommendations for the diagnosis and treatment of
      influenza from the Centers for Disease Control and Prevention (CDC).

PMID- 24033623
TI  - Effect of barcode-assisted medication administration on emergency department
      medication errors.
AB  - OBJECTIVES: Barcode-assisted medication administration (BCMA) is technology with
      demonstrated benefit in reducing medication administration errors in hospitalized
      patients; however, it is not routinely used in emergency departments (EDs). EDs
      may benefit from BCMA, because ED medication administration is complex and error
      prone. METHODS: A naive observational study was conducted at an academic medical
      center implementing BCMA in the ED. The rate of medication administration errors
      was measured before and after implementing an integrated electronic medical
      record (EMR) with BCMA capacity. Errors were classified as wrong drug, wrong
      dose, wrong route of administration, or a medication administration with no
      physician order. The error type, severity of error, and medications associated
      with errors were also quantified. RESULTS: A total of 1,978 medication
      administrations were observed (996 pre-BCMA and 982 post-BCMA). The baseline
      medication administration error rate was 6.3%, with wrong dose errors
      representing 66.7% of observed errors. BCMA was associated with a reduction in
      the medication administration error rate to 1.2%, a relative rate reduction of
      80.7% (p < 0.0001). Wrong dose errors decreased by 90.4% (p < 0.0001), and
      medication administrations with no physician order decreased by 72.4% (p =
      0.057). Most errors discovered were of minor severity. Antihistamine medications
      were associated with the highest error rate. CONCLUSIONS: Implementing BCMA in
      the ED was associated with significant reductions in the medication
      administration error rate and specifically wrong dose errors. The results of this
      study suggest a benefit of BCMA on reducing medication administration errors in
      the ED.

PMID- 24033622
TI  - Computed tomography with intravenous contrast alone: the role of intra-abdominal
      fat on the ability to visualize the normal appendix in children.
AB  - BACKGROUND: Computed tomography (CT) with enteric contrast is frequently used to
      evaluate children with suspected appendicitis. The use of CT with intravenous
      (IV) contrast alone (CT IV) may be sufficient, however, particularly in patients
      with adequate intra-abdominal fat (IAF). OBJECTIVES: The authors aimed 1) to
      determine the ability of radiologists to visualize the normal (nondiseased)
      appendix with CT IV in children and to assess whether IAF adequacy affects this
      ability and 2) to assess the association between IAF adequacy and patient
      characteristics. METHODS: This was a retrospective 16-center study using a
      preexisting database of abdominal CT scans. Children 3 to 18 years who had CT IV
      scan and measured weights and for whom appendectomy history was known from
      medical record review were included. The sample was chosen based on age to yield
      a sample with and without adequate IAF. Radiologists at each center reread their
      site's CT IV scans to assess appendix visualization and IAF adequacy. IAF was
      categorized as "adequate" if there was any amount of fat completely surrounding
      the cecum and "inadequate" if otherwise. RESULTS: A total of 280 patients were
      included, with mean age of 10.6 years (range = 3.1 to 17.9 years). All 280 had no
      history of prior appendectomy; therefore, each patient had a presumed normal
      appendix. A total of 102 patients (36.4%) had adequate IAF. The proportion of
      normal appendices visualized with CT IV was 72.9% (95% confidence interval [CI] =
      67.2% to 78.0%); the proportions were 89% (95% CI = 81.5% to 94.5%) and 63% (95%
      CI = 56.0% to 70.6%) in those with and without adequate IAF (95% CI for
      difference of proportions = 16% to 36%). Greater weight and older age were
      strongly associated with IAF adequacy (p < 0.001), with weight appearing to be a
      stronger predictor, particularly in females. Although statistically associated,
      there was noted overlap in the weights and ages of those with and without
      adequate IAF. CONCLUSIONS: Protocols using CT with IV contrast alone to visualize
      the appendix can reasonably include weight, age, or both as considerations for
      determining when this approach is appropriate. However, although IAF will more
      frequently be adequate in older, heavier patients, highly accurate prediction of
      IAF adequacy appears challenging solely based on age and weight.

PMID- 24033624
TI  - Evaluating current patterns of assessment for self-harm in emergency departments:
      a multicenter study.
AB  - OBJECTIVES: The objective was to describe self-harm assessment practices in U.S.
      emergency departments (EDs) and to identify predictors of being assessed.
      METHODS: This was a prospective observational cohort study of adults presenting
      to eight U.S. EDs. A convenience sample of adults presenting to the EDs during
      covered research shifts was entered into a study log. Self-harm assessment was
      defined as ED documentation of suicide attempt; suicidal ideation; or nonsuicidal
      self-injury thoughts, behaviors, or both. Institution characteristics were
      compared relative to percentage assessed. To identify predictive patient
      characteristics, multivariable generalized linear models were created controlling
      for weekend presentation, time of presentation, age, sex, and race and ethnicity.
      RESULTS: Among 94,354 charts, self-harm assessment ranged from 3.5% to 31%,
      except for one outlying site at 95%. Overall, 26% were assessed (11% excluding
      the outlying site). Current self-harm was present in 2.7% of charts. Sites with
      specific self-harm assessment policies had higher assessment rates. In the
      complete model, adjusted risk ratios (aRR) for assessment included age >= 65
      years (0.56, 95% confidence interval [CI] = 0.35 to 0.92) and male sex (1.17, 95%
      CI = 1.10 to 1.26). There was an interaction between these variables in the
      smaller model (excluding outlying site), with males < 65 years of age being more
      likely to be assessed (aRR = 1.14, 95% CI = 1.02 to 1.37). CONCLUSIONS: Emergency
      department assessment of self-harm was highly variable among institutions.
      Presence of specific assessment policies was associated with higher assessment
      rates. Assessment varied based upon patient characteristics. The identification
      of self-harm in 2.7% of ED patients indicates that a substantial proportion of
      current risk of self-harm may go unidentified, particularly in certain patient
      groups.

PMID- 24033625
TI  - Frequency of pregnancy testing among adolescent emergency department visits.
AB  - OBJECTIVES: The objective was to estimate the frequency of pregnancy testing
      among adolescent emergency department (ED) patients and to determine factors
      associated with testing. METHODS: This was a retrospective cross-sectional study
      using the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 2005
      through 2009 of ED visits by females ages 14 to 21 years. The frequency of
      pregnancy testing among all visits was estimated for potential reproductive
      health complaints and for those associated with exposure to potentially
      teratogenic radiation. Multivariable logistic regression modeling was performed
      to calculate adjusted probabilities and odds ratios (ORs) with 95% confidence
      intervals (CIs) to evaluate factors associated with pregnancy testing by patient
      characteristics. RESULTS: The authors identified 11,531 visits, representing an
      estimated 41.0 million female adolescent ED visits. Of these, 20.9% (95% CI =
      19.3% to 22.5%) included pregnancy testing. Among visits for potential
      reproductive health complaints and those associated with exposure to potentially
      teratogenic radiation, 44.5% (95% CI = 41.3% to 47.8%) and 36.7% (95% CI = 32.5%
      to 40.9%), respectively, included pregnancy testing. Among the entire study
      population, we found statistically significant differences in pregnancy testing
      by age, race or ethnicity, hospital admission, and geographic region (p < 0.001
      for all). CONCLUSIONS: A minority of female adolescent ED visits included
      pregnancy testing, even if patients presented with potential reproductive health
      complaints or received exposure to ionizing radiation. Small but statistically
      significant differences in pregnancy testing rates were noted based on age, race
      or ethnicity, ED disposition, and geographic region. Future studies should focus
      on designing quality improvement interventions to increase pregnancy testing in
      adolescent ED patients, especially among those in whom pregnancy complications or
      the risk of potentially teratogenic radiation exposure is higher.

PMID- 24033626
TI  - Waiver of informed consent in pediatric resuscitation research: a systematic
      review.
AB  - BACKGROUND: In critical care and emergency medicine research, obtaining consent
      can be problematic when patients present with life-threatening conditions. This
      issue is further complicated in children, as even while coherent, they are often
      incapable of making decisions regarding their own care. To enable the ethical
      conduct of research in such situations, the Food and Drug Administration (FDA) of
      the United States has set recommendations for the conduct of research employing a
      waiver of consent. These regulations have been termed "exception from informed
      consent," or EFIC. As this is an evolving concept with limited pediatric
      experience, the authors conducted a review to examine the conduct of emergency
      research in the absence of prospectively obtained informed consent. Our review
      focused both on opinions and on the ability to conduct research without informed
      consent in life-threatening situations. METHODS: A systematic review of the
      literature was undertaken in accordance with the PRISMA guidelines. Medline,
      CINAHL, and EMBASE databases were searched on January 9, 2013. Eligibility
      criteria included: 1) examined a method of conducting research in a life
      threatening situation, 2) involved a real or theoretical clinical situation, 3)
      involved patients less than 18 years of age or a substitute decision-maker, and
      4) reported at least one quantifiable outcome. The findings were synthesized
      qualitatively with the pertinent results summarized and discussed. RESULTS:
      Eleven articles matched the eligibility criteria. Six focused on community
      consultation and public disclosure, three focused on the feasibility of employing
      a waiver of consent, and two examined attitudes toward emergency research. Of the
      studies focusing on community consultation, four defined the community as
      previous or current patients and health care providers and administrators in the
      study's home institution; the other two defined the community as the general
      population. Although there was heterogeneity in study designs, settings, and
      outcome measures, overall 68% (3,219 of 4,767) of subjects surveyed supported the
      use of EFIC under select circumstances (individual study range = 50% to 92%).
      Caregiver support increased among those in whom the situation was a more possible
      reality (e.g., critical care unit patients) and varied by the scenario and method
      of presentation (e.g., bulleted handout vs. preferred). Several studies revealed
      that patient accrual and time to intervention are impeded when prospective
      informed consent is required. Finally, deferred consent, although endorsed and
      used outside of the United States, continues to raise important ethical
      questions, particularly related to the need and timing of disclosure.
      CONCLUSIONS: Limited data exist evaluating ethical issues in pediatric acute care
      resuscitation research. This review highlighted the fact that every proposal is
      unique and the method of obtaining consent (or waiver) requires careful
      consideration by local ethics committees. Particular attention must be paid to
      use of the population selected for community consultation. Several studies
      highlighted the need to consider the use of alternatives to prospective informed
      consent to enable the conduct of research in emergency departments (EDs) in life
      threatening situations. Future research should evaluate children's opinions on
      this topic.

PMID- 24033627
TI  - Global Emergency Medicine: a review of the literature from 2012.
AB  - OBJECTIVES: The Global Emergency Medicine Literature Review (GEMLR) conducts an
      annual search of peer-reviewed and grey literature relevant to global emergency
      medicine (EM) to identify, review, and disseminate the most important new
      research in this field to a worldwide audience of academics and clinical
      practitioners. METHODS: This year, our search identified 4,818 articles written
      in six languages. These articles were distributed among 20 reviewers for initial
      screening based on their relevance to the field of global EM. Two additional
      reviewers searched and screened the grey literature. A total of 224 articles were
      deemed appropriate by at least one reviewer and were approved by their editor for
      formal scoring of overall quality and importance. RESULTS: Of the 224 articles
      that met our predetermined inclusion criteria, 56% were categorized as Emergency
      Care in Resource-limited Settings, 18% as EM development, and 26% as Disaster and
      Humanitarian Response. A total of 28 articles received scores of 16 or higher and
      were selected for formal summary and critique. Inter-rater reliability for two
      reviewers using our scoring system was good, with an intraclass correlation
      coefficient of 0.625 (95% confidence interval = 0.512 to 0.711). CONCLUSIONS: In
      2012 there were more disaster and humanitarian response articles than in previous
      years. As in prior years, the majority of articles addressed the acute management
      of infectious diseases or the care of vulnerable populations such as children and
      pregnant women.

PMID- 24033628
TI  - Automated outcome classification of emergency department computed tomography
      imaging reports.
AB  - BACKGROUND: Reliably abstracting outcomes from free-text electronic health
      records remains a challenge. While automated classification of free text has been
      a popular medical informatics topic, performance validation using real-world
      clinical data has been limited. The two main approaches are linguistic (natural
      language processing [NLP]) and statistical (machine learning). The authors have
      developed a hybrid system for abstracting computed tomography (CT) reports for
      specified outcomes. OBJECTIVES: The objective was to measure performance of a
      hybrid NLP and machine learning system for automated outcome classification of
      emergency department (ED) CT imaging reports. The hypothesis was that such a
      system is comparable to medical personnel doing the data abstraction. METHODS: A
      secondary analysis was performed on a prior diagnostic imaging study on 3,710
      blunt facial trauma victims. Staff radiologists dictated CT reports as free text,
      which were then deidentified. A trained data abstractor manually coded the
      reference standard outcome of acute orbital fracture, with a random subset double
      coded for reliability. The data set was randomly split evenly into training and
      testing sets. Training patient reports were used as input to the Medical Language
      Extraction and Encoding (MedLEE) NLP tool to create structured output containing
      standardized medical terms and modifiers for certainty and temporal status.
      Findings were filtered for low certainty and past/future modifiers and then
      combined with the manual reference standard to generate decision tree classifiers
      using data mining tools Waikato Environment for Knowledge Analysis (WEKA) 3.7.5
      and Salford Predictive Miner 6.6. Performance of decision tree classifiers was
      evaluated on the testing set with or without NLP processing. RESULTS: The
      performance of machine learning alone was comparable to prior NLP studies
      (sensitivity = 0.92, specificity = 0.93, precision = 0.95, recall = 0.93, f-score
      = 0.94), and the combined use of NLP and machine learning showed further
      improvement (sensitivity = 0.93, specificity = 0.97, precision = 0.97, recall =
      0.96, f-score = 0.97). This performance is similar to, or better than, that of
      medical personnel in previous studies. CONCLUSIONS: A hybrid NLP and machine
      learning automated classification system shows promise in coding free-text
      electronic clinical data.

PMID- 24033629
TI  - In reply.

PMID- 24033630
TI  - Perceived danger while intoxicated uniquely contributes to driving after
      drinking.
AB  - BACKGROUND: Previous findings suggest that alcohol alters perceptions of risky
      behaviors such as drinking and driving. However, studies testing these
      perceptions as a predictor of drinking and driving typically measure these
      perceptions while participants are sober. This study tested whether the perceived
      danger of driving after drinking assessed while intoxicated was associated with
      increased willingness to drive and self-reported drinking-and-driving behavior
      over and above perceptions assessed while sober. Additionally, we tested the
      effect of acute tolerance on the perceived danger of driving after drinking
      assessed on the ascending and descending limbs of the breath alcohol
      concentration (BrAC) curve. METHODS: Eighty-two young adults attended 2
      counterbalanced laboratory sessions. In one session, participants consumed a
      moderate dose of alcohol (men: 0.72 g/kg, women: 0.65 g/kg) and reported their
      perceived danger of driving and willingness to drive at multiple points across
      the BrAC curve. On a separate occasion, participants remained sober and appraised
      the dangerousness of driving at a hypothetical, illegal BrAC. RESULTS:
      Perceptions of the dangerousness of driving following alcohol administration were
      associated with increased willingness to drive and higher rates of self-reported
      drinking-and-driving behavior over and above perceptions reported when sober.
      Furthermore, perceived danger was reduced on the descending limb of the BrAC
      curve, compared with the ascending limb, suggesting the occurrence of acute
      tolerance. CONCLUSIONS: Results from this study suggest that intoxicated
      perceptions are uniquely associated with drinking-and-driving decisions and that
      the perceived danger of drinking and driving is lower on the descending limb of
      the BrAC curve. Efforts to prevent alcohol-impaired driving have focused on
      increasing awareness of the danger of driving after drinking. Prevention efforts
      may be enhanced by educating drivers about how intoxication can alter perceived
      danger, and interventions may benefit from targeting perceptions of dangerousness
      while individuals are intoxicated in addition to when they are sober.

PMID- 24033631
TI  - Single or repeated gonadotropin-releasing hormone agonist treatment avoids
      hysterectomy in premenopausal women with large symptomatic fibroids with no
      effects on sexual function.
AB  - AIM: The aim of our study was to explore the effects on symptoms and female
      sexual function of the medical management with gonadotropin-releasing hormone
      agonist (GnRHa) in women of more than 45 years old compared to surgical
      management. METHODS: Women with symptomatic uterine fibroids were enrolled to
      participate to the present open-label study. We offered two different treatment
      options: medical with GnRHa for 6 months (group A) or hysterectomy (group B). The
      patients were reviewed in follow-up for 24 months. The impact of medical or
      surgical therapy on sexual life was evaluated. RESULTS: No significant
      differences were found in population characteristics between the two groups.
      GnRHa treatment was efficient in reducing symptoms in 88% of patients but 22% of
      patients needed adjunctive cycles of medical therapy. After 24 months, 16% of the
      patients did not complete the study. The failure percentage of the medical
      treatment was 12%. No severe side-effects were recorded, and eight patients had
      reached menopause. No significant differences were observed in the Female Sexual
      Function Index score in each domain between the medical and surgical groups, with
      total scores of 18.94 +/- 10.16 and 22.00 +/- 8.86, respectively (mean +/-
      standard deviation), and the prevalence of dysfunction was 12% and 22%,
      respectively, similar to the general population of the same age. CONCLUSION: We
      found that medical therapy with GnRHa is a satisfactory alternative to surgery
      for fibroids in women of more than 45 years old.

PMID- 24033632
TI  - A closer look at the evidence for sex differences in the genetic and
      environmental influences on gambling in the national longitudinal study of
      adolescent health: from disordered to ordered gambling.
AB  - BACKGROUND AND AIMS: To reconcile an inconsistency in the disordered gambling
      literature by revisiting a previous study that claimed to find evidence for large
      gender differences in the magnitude of genetic and environmental influences.
      DESIGN: Univariate structural equation twin models were fitted to decompose the
      variation in gambling behavior into additive genetic, shared environmental and
      unique environmental influences. SETTING: United States. PARTICIPANTS:
      Participants were 1196 same-sex and unlike-sex twins (18-28 years of age, 49%
      male, 51% female) from the National Longitudinal Study of Adolescent Health (Add
      Health). MEASUREMENTS: Eight questions about normative and problematic gambling
      involvement were assessed by in-person interview. Although disordered gambling
      symptoms were assessed, the number of individuals who were administered these
      questions precluded twin analysis, including analysis of potential gender
      differences. Of the eight questions, only three were deemed usable for twin
      analysis-these were all questions about normative gambling involvement. FINDINGS:
      Individual differences in (non-disordered) gambling involvement were explained
      completely by family [C = 38% (30-46%)] and unique environmental factors [E = 62%
      (54-70%)]. There was no evidence for genetic factors (A = 0), nor was there
      evidence for sex differences (Deltachi(2) = 1.23, d.f. = 2, P = 0.54).
      CONCLUSIONS: There appears to be no evidence for gender differences in the
      genetic contributions to disordered gambling. Family environment appears to play
      a significant role in explaining individual differences in (non-disordered)
      gambling involvement among emerging adults.

PMID- 24033633
TI  - Antibiotic sensitivity and resistance patterns in pediatric staphylococcal
      scalded skin syndrome.
AB  - Historical resistance patterns often guide empiric antibiotic choices in
      staphylococcal scalded skin syndrome (SSSS), but little is known about the
      difference in susceptibility between SSSS and other childhood staphylococcal
      infections. A retrospective chart review of culture-confirmed cases of SSSS seen
      in the inpatient dermatology consultation service at the Children's Hospital of
      Philadelphia between 2005 and 2011 was performed. Most cases of SSSS at our
      institution are due to oxacillin-susceptible Staphylococcus aureus, and
      approximately half of the cases are due to clindamycin-resistant strains.
      Clindamycin and a penicillinase-resistant penicillin are suggested as empiric
      treatment for SSSS until culture susceptibility data are available to guide
      therapy. 

PMID- 24033634
TI  - Cancer therapeutics revisited; novel drugs targeting cell signalling pathways,
      genome wide association studies and other trials and tribulations.

PMID- 24033635
TI  - Repeatability of the combined glucose-insulin tolerance test and the effect of a
      stressor before testing in horses of 2 breeds.
AB  - BACKGROUND: The increasing number of horses diagnosed with insulin resistance
      (IR) and the suggested link between IR and laminitis has highlighted the need to
      accurately diagnose IR in clinical practice. HYPOTHESIS/OBJECTIVES: The aim of
      the study was to evaluate the repeatability of the combined glucose-insulin
      tolerance test (CGIT) as well as to determine the effect of 2 different breeds
      and the effect of a stressor on the test results. ANIMALS: Clinically normal
      horses, 9 Standardbred horses and 9 Icelandic horses. METHODS: Prospective
      clinical nonrandomized trial. The CGIT was performed on all horses on 2 occasions
      3 weeks apart. An additional CGIT was performed on four of the Standardbred and
      four of the Icelandic horses after transportation to a new environment (stressor)
      the day before testing. RESULTS: Calculated parameters for the glucose curve of
      the CGIT had low repeatability, whereas the parameters for the insulin curve had
      high repeatability. There was an effect of breed (Standarbred versus Icelandic
      horse) as well as stress on the glucose dynamics, but not on the insulin dynamics
      of the CGIT. CONCLUSION AND CLINICAL IMPORTANCE: Repeatability of the glucose
      dynamics of the CGIT is low. In addition, there appears to be breed differences
      in the glucose dynamics. It is therefore suggested that diagnosis of IR should
      not be made solely based on results from the glucose curve of the CGIT.

PMID- 24033636
TI  - A systematic review and quantitative analysis of neurocognitive outcomes in
      children with four chronic illnesses.
AB  - BACKGROUND: Concern has been expressed that infants and children exposed to
      uneventful surgery and anesthesia may incur neurological injury that becomes
      manifest in poor scholastic performance or future learning difficulties. A recent
      meta-analysis of seven clinical studies examined the relationship between
      learning or behavior difficulties and pediatric exposure to anesthesia/surgery
      and reported an odds ratio of 1.4; however, the level of association and causal
      factors remain unclear. The purpose of our study is to provide context to the
      pediatric anesthesia neurotoxicity question by reviewing the evidence linking
      four childhood illnesses with neurocognitive development. In the present review,
      we have sought to quantify the magnitude of the impact of chronic illness on
      neurocognitive development through a systematic review of publications that
      report the developmental trajectory of patients with four childhood diseases:
      cystic fibrosis (CF), hemophilia A, end-stage renal disease (ESRD) and end-stage
      liver disease (ESLD). METHODS: Studies were identified by searching the
      electronic databases OVID MEDLINE and Pubmed and scanning reference lists of
      articles by two authors. Limits were applied to the English language and to
      humans. We used the following search terms: CF, hemophilia A, ESRD, ESLD in
      combination with academic performance, educational status, educational
      measurement, learning, achievement, developmental delay, learning disabilities,
      intellectual disabilities, behavioral disorders, intelligence quotient (IQ),
      cognition, school problems, absenteeism, school attendance, anxiety, learning
      regression, or developmental regression. The search strategy was reviewed
      independently by all four authors. Eligibility assessment was performed
      independently in an unblinded standardized manner by two authors who chose
      relevant articles from the overall search results by scanning the titles and
      abstracts of articles and from the references within citations. The full-text
      publications were reviewed by all four authors. All pertinent data related to the
      objectives were collected and independently reviewed by two authors. The data
      were summarized in the form reported in the studies. When possible, reported data
      were submitted to analysis with the Mantel-Haenszel method using a random effects
      model. Analyses were performed using the Review Manager computer program.
      RESULTS: In the studies retrieved, the main outcomes were measures of
      intellectual or cognitive characteristics, as exemplified by the Wechsler battery
      of tests. Reporting of measures of achievement (for example, GPA) was rare.
      Children with CF and hemophilia A did not appear disadvantaged by their disease
      as general intelligence levels were comparable with the general population norms.
      In children with ESRD, mean IQ reported during dialysis improved after
      transplantation. Although they improved relative to their pretransplantation
      cognitive functioning, children with ESLD who received transplants are
      approximately eight IQ points below the population norm. CONCLUSIONS: Overall,
      the results suggest that the burden of chronic childhood illness, by itself, does
      not impair cognitive development in children with hemophilia A and CF. Children
      with ESRD and ESLD, despite optimal management, show a mild cognitive deficit
      compared with the population norm. Given the impact of these four specific
      chronic illnesses on neurocognitive outcome in children and the improvement in IQ
      post-transplant in both ESRD and ESLD, the results suggest that the effect of an
      uncontrolled confounding illness on neurocognitive development is small.

PMID- 24033637
TI  - Effects of magnetic nanoparticle-incorporated human bone marrow-derived
      mesenchymal stem cells exposed to pulsed electromagnetic fields on injured rat
      spinal cord.
AB  - Transplanting mesenchymal stem cells into injured lesions is currently under
      study as a therapeutic approach for spinal cord injury. In this study, the
      effects of a pulsed electromagnetic field (PEMF) on injured rat spinal cord were
      investigated in magnetic nanoparticle (MNP)-incorporated human bone marrow
      derived mesenchymal stem cells (hBM-MSCs). A histological analysis revealed
      significant differences in MNP-incorporated cell distribution near the injured
      site under the PEMF in comparison with that in the control group. We confirmed
      that MNP-incorporated cells were widely distributed in the lesions under PEMF.
      The results suggest that MNP-incorporated hBM-MSCs were guided by the PEMF near
      the injured site, and that PEMF exposure for 8 H per day over 4 weeks promoted
      behavioral recovery in spinal cord injured rats. The results show that rats with
      MNP-incorporated hBM-MSCs under a PEMF were more effective on the Basso, Beattie,
      and Bresnahan behavioral test and suggest that the PEMF enhanced the action of
      transplanted cells for recovery of the injured lesion.

PMID- 24033638
TI  - Multiple lineages of Avian malaria parasites (Plasmodium) in the Galapagos
      Islands and evidence for arrival via migratory birds.
AB  - Haemosporidian parasites in the genus Plasmodium were recently detected through
      molecular screening in the Galapagos Penguin (Spheniscus mendiculus). We
      summarized results of an archipelago-wide screen of 3726 endemic birds
      representing 22 species for Plasmodium spp. through a combination of molecular
      and microscopy techniques. Three additional Plasmodium lineages were present in
      Galapagos. Lineage A-infected penguins, Yellow Warblers (Setophaga petechia
      aureola), and one Medium Ground Finch (Geospiza fortis) and was detected at
      multiple sites in multiple years [corrected]. The other 3 lineages were each
      detected at one site and at one time; apparently, they were transient infections
      of parasites not established on the archipelago. No gametocytes were found in
      blood smears of infected individuals; thus, endemic Galapagos birds may be dead
      end hosts for these Plasmodium lineages. Determining when and how parasites and
      pathogens arrive in Galapagos is key to developing conservation strategies to
      prevent and mitigate the effects of introduced diseases. To assess the potential
      for Plasmodium parasites to arrive via migratory birds, we analyzed blood samples
      from 438 North American breeding Bobolinks (Dolichonyx oryzivorus), the only
      songbird that regularly migrates through Galapagos. Two of the ephemeral
      Plasmodium lineages (B and C) found in Galapagos birds matched parasite sequences
      from Bobolinks. Although this is not confirmation that Bobolinks are responsible
      for introducing these lineages, evidence points to higher potential arrival rates
      of avian pathogens than previously thought. Linajes Multiples de Parasitos de
      Malaria Aviar (Plasmodium) en las Islas Galapagos y Evidencia de su Arribo por
      Medio de Aves Migratorias.

PMID- 24033639
TI  - Inguinal hernia containing a kidney with a duplicated system: an exceptionally
      rare case.
AB  - An inguinal hernia is a commonly encountered surgical case, with multiple unusual
      contents being reported. We present an exceptionally rare case of an inguinal
      hernia. Computed tomography imaging of the 62-year-old male patient showed a
      large left inguinal hernia extending into the left scrotum that contained a
      duplicated left kidney. There was an associated large left hydrocele and
      incidental non-obstructive nephrolithiasis. Left nephropexy, left orchiectomy,
      and repair of the incarcerated left inguinal hernia with mesh placement via a
      preperitoneal (retroperitoneal) approach were performed. The patient was
      discharged to home on post-operative day 5 and the post-operative course was
      uneventful. We discuss a possible mechanism for this rare event. 

PMID- 24033640
TI  - Unsuccessful validation of 2004 model for predicting academic or behavioural
      limitations after childhood bacterial meningitis.
AB  - AIM: In 2004, a model identifying children at risk of academic or behavioural
      limitations after bacterial meningitis (BM) was presented. Risk factors were male
      gender, low birthweight, lower educational level of the father, Streptococcus
      pneumoniae, lower cerebrospinal fluid (CSF) leucocyte count, delay between
      admission and start of antibiotics, dexamethasone <2 days, seizures and prolonged
      fever. The aim of this study was to validate that prediction model in an
      independent cohort. METHODS: Academic or behavioural limitations were determined
      in 93 Dutch school-age BM survivors. Risk factors for limitations were obtained
      from medical files. Validation was performed by applying the model in the cohort,
      then assessing discrimination and goodness of fit. Multiple imputation techniques
      were used to deal with missing values. RESULTS: Although fit of the model
      appeared good when it came to similarity of expected and observed cases (p-value
      of the Hosmer-Lemeshow test 0.24-0.57), discrimination was poor. Area under the
      curve (AUC) of the receiver operated characteristics (ROC) curve of the model was
      0.83 (95% CI: 0.77-0.89) in the development cohort and 0.53 (95% CI: 0.41-0.65)
      in the validation cohort. CONCLUSION: External validation of the model was
      unsuccessful. It is not suitable for implementation in practice.

PMID- 24033641
TI  - Detection of bacterial DNA by PCR in dogs with stifle pathology.
AB  - OBJECTIVE: To determine presence of bacterial DNA in canine stifles with cranial
      cruciate ligament rupture (CCLR) and medial patellar luxation (MPL) compared to
      normal canine stifles (control). STUDY DESIGN: Prospective clinical study.
      ANIMALS: Dogs (n = 44). METHODS: Dogs of varying age, breed, sex, and weight
      residing in California were assessed for stifle pathology (CCLR, MPL, or normal
      control). Synovial fluid of all stifles was assessed for the presence of
      bacterial DNA using broad-ranging 16S rRNA primers and PCR. RESULTS: Bacterial
      DNA was detected in normal control stifles and those with CCLR and MPL. There
      were no statistical differences in the copy numbers of bacterial DNA in the
      stifle synovial fluid among groups (P > .05); however, synovial fluid specimens
      from dogs with stifle pathology (CCLR and MPL combined) tended to have higher
      copy numbers of bacterial DNA than those from controls (P = .06). There was no
      significant difference in the number of bacterial DNA between the CCLR and MPL
      groups (P = .57). The copy numbers of bacterial DNA had a weak positive
      significant correlation with the duration of lameness in CCLR group (P < .05).
      CONCLUSIONS: Increased detection of bacterial DNA in the stifle synovial fluid
      may indicate joint pathology but not be directly linked to a specific joint
      disease.

PMID- 24033643
TI  - Detection of a new OsHV-1 DNA strain in the healthy Pacific oyster, Crassostrea
      gigas Thunberg, from the Gulf of California.

PMID- 24033642
TI  - Involvement of homologous recombination in the synergism between cisplatin and
      poly (ADP-ribose) polymerase inhibition.
AB  - Poly (ADP-ribose) polymerase (PARP) plays a critical role in responding to DNA
      damage, by activating DNA repair pathways responsible for cellular survival.
      Inhibition of PARP is used to treat certain solid cancers, such as breast and
      ovarian cancers. However, its effectiveness with other solid cancers, such as
      esophageal squamous cell carcinoma (ESCC), has not been clarified. We evaluated
      the effects of PARP inhibition on the survival of human esophageal cancer cells,
      with a special focus on the induction and repair of DNA double-strand breaks. The
      effects were monitored by colony formation assays and DNA damage responses, with
      immunofluorescence staining of gammaH2AX and RAD51. We found that PARP inhibition
      synergized with cisplatin, and the cells were highly sensitive, in a similar
      manner to the combination of cisplatin and 5-fluorouracil (5-FU). Comparable
      increases in RAD51 foci formation were observed after each combined treatment
      with cisplatin and either 3-aminobenzamide (3-AB) or 5-FU in three human
      esophageal cancer cell lines, TE11, TE14, and TE15. In addition, decreasing the
      amount of RAD51 by RNA interference rendered the TE11 cells even more
      hypersensitive to these treatments. Our findings suggested that the homologous
      recombinational repair pathway may be involved in the synergism between cisplatin
      and either 3-AB or 5-FU, and that 3-AB and 5-FU may similarly modify the
      cisplatin-induced DNA damage to types requiring the recruitment of RAD51 proteins
      for their repair. Understanding these mechanisms could be useful for improving
      the clinical outcome of ESCC patients who suffer from aggressive disease that
      presently lacks effective treatment options. 

PMID- 24033644
TI  - Jugular valve incompetence in transient global amnesia. A problem revisited.
AB  - BACKGROUND AND PURPOSE: Previous studies have suggested that transient global
      amnesia (TGA) may be provoked by cerebral venous congestion due to a reflux
      during Valsalva maneuver (VM) caused by internal jugular venous valve
      incompetence (IJVVI). We investigated the hemodynamic consequences of postural
      changes on IJVVI and on intracranial veins in patients with TGA and control
      subjects. MATERIALS AND METHODS: IJVVI was assessed by means of extracranial
      color-coded duplex sonography during VM in 28 patients with TGA and 25 controls.
      The basal vein Rosenthal was examined by transcranial color-coded sonography
      registering flow velocities (FV) at rest and during VM. These measurements were
      performed in the supine and in a sitting position. RESULTS: IJVVI was identified
      in supine position in 19/28 (68%) of TGA patients and in 7/25 (28%) of controls
      (P < .05). Body position had no effect on the detection of IJVVI. Intracranial
      venous FV at rest and during VM did neither differ between patients and controls,
      nor between persons with and without IJVVI. CONCLUSIONS: Consistent with results
      of other groups, we found a significantly higher rate of IJVVI in TGA patients
      compared to controls. However, we found no differences of intracranial venous
      circulation between groups nor an effect of body position. This sheds doubt on
      the assumption of a causative effect of IJVVI in TGA.

PMID- 24033645
TI  - Comparison of hepatic adaptation in extreme metabolic phenotypes observed in
      early lactation dairy cows on-farm.
AB  - The aim was to study the variation in metabolic responses in early-lactating
      dairy cows (n = 232) on-farm that were pre-selected for a high milk fat content
      (>45 g/l) and a high fat/protein ratio in milk (>1.5) in their previous
      lactation. Blood was assayed for concentrations of metabolites and hormones.
      Liver was measured for mRNA abundance of 25 candidate genes encoding enzymes and
      receptors involved in gluconeogenesis (6), fatty acid beta-oxidation (6), fatty
      acid and triglyceride synthesis (5), cholesterol synthesis (4), ketogenesis (2)
      and the urea cycle (2). Two groups of cows were formed based on the plasma
      concentrations of glucose, non-esterified fatty acids (NEFA) and beta
      hydroxybutyric acid (BHBA) (GRP+, high metabolic load; glucose <3.0 mm, NEFA >300
      MUm and BHBA >1.0 mm, n = 30; GRP-, low metabolic load; glucose >3.0 mm, NEFA
      <300 MUm and BHBA <1.0 mm, n = 30). No differences were found between GRP+ and
      GRP- for the milk yield at 3 weeks post-partum, but milk fat content was higher
      (p < 0.01) for GRP+ than for GRP-. In week 8 post-partum, milk yield was higher
      in GRP+ in relation to GRP- (37.5 vs. 32.5 kg/d; p < 0.01). GRP+ in relation to
      GRP- had higher (p < 0.001) NEFA and BHBA and lower glucose, insulin, IGF-I, T3 ,
      T4 concentrations (p < 0.01). The mRNA abundance of genes related to
      gluconeogenesis, fatty acid beta-oxidation, fatty acid and triglyceride
      synthesis, cholesterol synthesis and the urea cycle was different in GRP+
      compared to GRP- (p < 0.05), although gene transcripts related to ketogenesis
      were similar between GRP+ and GRP-. In conclusion, high metabolic load post
      partum in dairy cows on-farm corresponds to differences in the liver in relation
      to dairy cows with low metabolic load, even though all cows were pre-selected for
      a high milk fat content and fat/protein ratio in milk in their previous
      lactation. 

PMID- 24033646
TI  - The association between neutropenia and prognosis in stage III colorectal cancer
      patients receiving adjuvant chemotherapy.
AB  - Neutropenia during chemotherapy has been reported to be a predictor of better
      survival in patients with several types of cancer, although there are no reports
      on stage III colorectal cancer (CRC). The purpose of this study was to examine
      the association between neutropenia and prognosis in stage III CRC patients
      receiving adjuvant chemotherapy consisting of oral uracil and tegafur (UFT) plus
      leucovorin (LV). We retrospectively analysed 123 patients with stage III CRC who
      received UFT/LV as adjuvant chemotherapy. The end-point was disease-free survival
      (DFS). Survival curves of the two categories (neutropenia absent vs. present)
      were estimated using the Kaplan-Meier method and compared by the log-rank test.
      We estimated the hazard ratio (HR) for DFS according to neutropenia after
      adjustment for covariates by multivariate analyses using Cox's regression
      analysis. A total of 33 (26.8%) patients experienced neutropenia. Patients
      without neutropenia showed a significantly lower DFS than those with neutropenia
      (3-year DFS 57.3% vs. 81.2%, P = 0.0213). By multivariate analysis, neutropenia
      and histological type were independent prognostic factors, with HR of 0.410
      (neutropenia absent vs. present, P = 0.045) and 4.793 (well to moderately
      differentiated vs. poorly differentiated, P = 0.004) respectively. We
      demonstrated that neutropenia occurring during adjuvant chemotherapy consisting
      of UFT/LV may be a prognostic factor of recurrence in stage III CRC patients. 

PMID- 24033647
TI  - Use of eye-pointing by children with cerebral palsy: what are we looking at?
AB  - BACKGROUND: Children with cerebral palsy often show significant communication
      impairment due to limited or absent speech. Further, motor impairment can
      restrict the use of movement, including pointing, to signal interest and intent.
      For some children, controlled gaze can be an effective 'point-substitute': such
      'eye-pointing' can be used to request items, establish mutual interest in an
      event, or select vocabulary within an alternative or augmentative communication
      (ACC) system. However, in clinical practice there is a lack of clarity about how
      the term 'eye-pointing' is used, how 'eye-pointing' is recognized or how it
      relates to social development. AIMS: To present a clinical description of the
      term 'eye-pointing' with reference to children with severe cerebral palsy who
      cannot speak or finger-point. To consider this description within a wider
      discussion of the importance of gaze in communication development. METHODS &
      PROCEDURES: Cumulative clinical observations during assessment of children
      referred to a specialist multidisciplinary communication clinic have provoked
      discussion between the authors on what factors precipitate use of the term 'eye
      pointing' in young children with severe cerebral palsy. In particular, discussion
      has centred on whether use of the term is appropriate in individual cases and
      whether guidance is available about how gaze should be observed in this
      developmentally vulnerable group of children. A literature search was also
      conducted in order to explore whether the use and meaning of the term is
      established. CONCLUSIONS & IMPLICATIONS: In interactions with non-speaking
      children, determining whether a child is using eye-gaze communicatively requires
      observation and interpretation of several factors. These processes will be
      informed by reflection on what is known about other aspects of the child's
      communication and interaction skills. Within the literature, the term 'eye
      pointing' is sometimes used when describing the communication functions of
      individuals using augmentative and alternative communication (AAC) systems, and
      is occasionally qualified by a definition. No papers have been found that set out
      a clinical description universally applicable to children with severe motor
      impairment. Moreover, guidance is lacking on how possible episodes of 'eye
      pointing' might be confidently distinguished from other episodes of directed gaze
      in young, developing communicators. The discussion of the term makes reference to
      the importance of gaze in early communication development, and explores factors
      that might influence gaze and its interpretation in young children with cerebral
      palsy. A description of eye-pointing for this group is offered. The authors
      suggest that this will bring practical benefits to those supporting the
      communication development of children with severe cerebral palsy.

PMID- 24033648
TI  - Child speech, language and communication need re-examined in a public health
      context: a new direction for the speech and language therapy profession.
AB  - BACKGROUND: Historically speech and language therapy services for children have
      been framed within a rehabilitative framework with explicit assumptions made
      about providing therapy to individuals. While this is clearly important in many
      cases, we argue that this model needs revisiting for a number of reasons. First,
      our understanding of the nature of disability, and therefore communication
      disabilities, has changed over the past century. Second, there is an increasing
      understanding of the impact that the social gradient has on early communication
      difficulties. Finally, understanding how these factors interact with one other
      and have an impact across the life course remains poorly understood. AIMS: To
      describe the public health paradigm and explore its implications for speech and
      language therapy with children. METHODS & PROCEDURES: We test the application of
      public health methodologies to speech and language therapy services by looking at
      four dimensions of service delivery: (1) the uptake of services and whether those
      children who need services receive them; (2) the development of universal
      prevention services in relation to social disadvantage; (3) the risk of over
      interpreting co-morbidity from clinical samples; and (4) the overlap between
      communicative competence and mental health. OUTCOMES & CONCLUSIONS: It is
      concluded that there is a strong case for speech and language therapy services to
      be reconceptualized to respond to the needs of the whole population and according
      to socially determined needs, focusing on primary prevention. This is not to
      disregard individual need, but to highlight the needs of the population as a
      whole. Although the socio-political context is different between countries, we
      maintain that this is relevant wherever speech and language therapists have a
      responsibility for covering whole populations. Finally, we recommend that speech
      and language therapy services be conceptualized within the framework laid down in
      The Ottawa Charter for Health Promotion.

PMID- 24033649
TI  - Adapting to conversation with semantic dementia: using enactment as a
      compensatory strategy in everyday social interaction.
AB  - BACKGROUND: Studies to date in semantic dementia have examined communication in
      clinical or experimental settings. There is a paucity of research describing the
      everyday interactional skills and difficulties seen in this condition. AIMS: To
      examine the everyday conversation, at home, of an individual with semantic
      dementia. METHODS & PROCEDURES: A 71-year-old man with semantic dementia and his
      wife were given a video camera and asked to record natural conversation in the
      home situation with no researcher present. Recordings were also made in the home
      environment, with the individual with semantic dementia in conversation with a
      member of the research team. Conversation analysis was used to transcribe and
      analyse the data. Recurring features were noted to identify conversational
      patterns. OUTCOMES & RESULTS: Analysis demonstrated a repeated practice by the
      speaker with semantic dementia of acting out a diversity of scenes (enactment).
      As such, the speaker regularly used direct reported speech along with
      paralinguistic features (such as pitch and loudness) and non-vocal communication
      (such as body posture, pointing and facial expression) as an adaptive strategy to
      communicate with others in conversation. CONCLUSIONS & IMPLICATIONS: This case
      shows that while severe difficulties may be present on neuropsychological
      assessment, relatively effective communicative strategies may be evident in
      conversation. A repeated practice of enactment in conversation allowed this
      individual to act out, or perform what he wanted to say, allowing him to generate
      a greater level of meaningful communication than his limited vocabulary alone
      could achieve through describing the events concerned. Such spontaneously
      acquired adaptive strategies require further attention in both research and
      clinical settings in semantic dementia and analysis of interaction in this
      condition, using conversation analysis, may be helpful.

PMID- 24033650
TI  - Using computers to enable self-management of aphasia therapy exercises for word
      finding: the patient and carer perspective.
AB  - BACKGROUND: Speech and language therapy (SLT) for aphasia can be difficult to
      access in the later stages of stroke recovery, despite evidence of continued
      improvement with sufficient therapeutic intensity. Computerized aphasia therapy
      has been reported to be useful for independent language practice, providing new
      opportunities for continued rehabilitation. The success of this option depends on
      its acceptability to patients and carers. AIMS: To investigate factors that
      affect the acceptability of independent home computerized aphasia therapy
      practice. METHODS & PROCEDURES: An acceptability study of computerized therapy
      was carried out alongside a pilot randomized controlled trial of computer aphasia
      therapy versus usual care for people more than 6 months post-stroke. Following
      language assessment and computer exercise prescription by a speech and language
      therapist, participants practised three times a week for 5 months at home with
      monthly volunteer support. Semi-structured interviews were conducted with 14
      participants who received the intervention and ten carers (n = 24). Questions
      from a topic guide were presented and answered using picture, gesture and written
      support. Interviews were audio recorded, transcribed verbatim and analysed
      thematically. Three research SLTs identified and cross-checked themes and
      subthemes emerging from the data. OUTCOMES & RESULTS: The key themes that emerged
      were benefits and disadvantages of computerized aphasia therapy, need for help
      and support, and comparisons with face-to-face therapy. The independence,
      flexibility and repetition afforded by the computer was viewed as beneficial and
      the personalized exercises motivated participants to practise. Participants and
      carers perceived improvements in word-finding and confidence-talking. Computer
      practice could cause fatigue and interference with other commitments. Support
      from carers or volunteers for motivation and technical assistance was seen as
      important. Although some participants preferred face-to-face therapy, using a
      computer for independent language practice was perceived to be an acceptable
      alternative. CONCLUSIONS & IMPLICATIONS: Independent computerized aphasia therapy
      is acceptable to stroke survivors. Acceptability can be maximized by tailoring
      exercises to personal interests of the individual, ensuring access to support and
      giving consideration to fatigue and life style when recommending practice
      schedules.

PMID- 24033651
TI  - Event narratives in 11-14 year olds with autistic spectrum disorder.
AB  - BACKGROUND: Children with autistic spectrum disorder (ASD) are known to have
      difficulties in narrative language and especially with use of evaluative
      enrichment devices. However, little is known about their production of event
      narratives. AIMS: To establish if children with ASD differ from typically
      developing peers in their production of general and specific event narratives,
      and, if so, how this might be affected by levels of oral language. METHODS &
      PROCEDURES: Performance on general and specific event narrative tasks of 27 high
      functioning children with ASD, aged 11-14 years, was compared with that of
      language- and age-matched groups of typically developing children. Narratives
      were coded for structural and evaluative language measures. OUTCOMES & RESULTS:
      The general and specific event narratives of the ASD group differed from those of
      both comparison groups in structural language measures. They were shorter,
      contained fewer different word roots and had shorter mean length of utterances.
      In evaluative measures they differed from those of the typically developing age
      match group but not the younger language match group in the number of causal
      statements made in both event conditions, and in mental state references and
      evaluative devices in the specific event narrative condition. CONCLUSIONS &
      IMPLICATIONS: Children with ASD display specific difficulties with the use of
      grammar and vocabulary in event narratives which cannot be explained in terms of
      language levels. However, the use of evaluative devices was commensurate with
      oral language levels. Implications for intervention are discussed.

PMID- 24033652
TI  - Markers for persistent specific expressive language delay in 3-4-year-olds.
AB  - BACKGROUND: Identifying 3-4-year-olds who are most at risk of persisting language
      difficulties, and possibly specific language impairment (SLI), is difficult due
      to the natural variation of language in young children. In older children,
      markers for SLI have been identified that differentiate between children with and
      without SLI. It is not known whether these markers can be used at an earlier age
      to identify children most at risk of persisting language difficulties. AIMS: To
      identify possible risk markers of current status that distinguish children who
      have specific expressive language delay (SELD) from the variation observed in
      normally developing children at age 3;0-4;0 and 4;0-5;0. To determine the most
      suitable measure(s) that would predict which children with SELD at age 3;0-4;0
      were likely to have persistent expressive language delay (PELD) at age 4;0-5;0.
      METHODS & PROCEDURES: Forty-seven children with SELD and 47 children with typical
      language development (TLD) were assessed on language, nonverbal IQ and marker
      tasks at age 3;0-4;0 (baseline). Ninety-one children were reassessed on the
      measures one year later (follow-up). At both time points, the marker tasks were
      compared with a reference standard (Expressive Communication subscale (EC) of the
      Preschool Language Scale-3 (PLS-3) (UK)) to determine the most useful marker for
      identifying children with SELD. Possible predictors were examined to determine
      the most suitable measure(s) that would predict which children with SELD at
      baseline were likely to have PELD at follow-up. OUTCOME & RESULTS: A modified
      version of Recalling Sentences, a subtest of the Clinical Evaluation of Language
      Fundamentals (CELF)-Preschool UK, was the most useful marker for identifying
      children with SELD at baseline and at follow-up. Thirty-five (76.1%) of the 46
      children with SELD at baseline had PELD at follow-up. Performance on the Auditory
      Comprehension (AC) and EC subscales of the PLS-3 (UK) and on modified Recalling
      Sentences at age 3;0-4;0 were predictors of PELD at age 4;0-5;0. CONCLUSIONS &
      IMPLICATIONS: A modified Recalling Sentences task was a good risk marker for SELD
      at age 3;0-4;0 and SELD at age 4;0-5;0. PLS-3 AC, PLS-3 EC and modified Recalling
      Sentences at baseline were the best predictors of PELD. The use of modified
      Recalling Sentences as a predictive marker requires confirmation.

PMID- 24033653
TI  - Clinical markers in Italian-speaking children with and without specific language
      impairment: a study of non-word and real word repetition as predictors of
      grammatical ability.
AB  - BACKGROUND: In many languages a weakness in non-word repetition serves as a
      useful clinical marker of specific language impairment (SLI) in children.
      However, recent work in Italian has shown that the repetition of real words may
      also have clinical utility. For young typically developing Italian children, real
      word repetition is more predictive of particular grammatical abilities than is
      non-word repetition. This finding is important because these particular
      grammatical abilities--the production of present-tense third-person plural
      inflections and direct-object clitic pronouns--are precisely those that are
      problematic for Italian-speaking children with SLI. Along with their grammatical
      requirements, these two morpheme types present a significant
      phonological/prosodic challenge for these children. AIMS: To replicate the
      findings with young typically developing Italian children and to determine
      whether real word repetition is also more predictive of the use of these two
      morpheme types than is non-word repetition in a group of Italian-speaking
      children with SLI. METHODS & PROCEDURES: Seventeen Italian-speaking children with
      SLI and 17 younger typically developing children matched for mean length of
      utterance participated in tasks of real word and non-word repetition as well as
      tasks requiring the production of direct-object clitic pronouns and present-tense
      third-person plural inflections. OUTCOMES & RESULTS: Children with SLI were less
      accurate than their younger peers on all measures. Importantly, for the younger
      typically developing children, real word repetition explained a significant
      amount of variance in the use of third-person plural inflections and direct
      object clitic pronouns. For the children with SLI, in contrast, non-word
      repetition was a significant predictor, whereas real word repetition was not a
      contributing factor. CONCLUSIONS & IMPLICATIONS: It is argued that in Italian
      SLI, the grammatical details showing the greatest weakness present
      phonological/prosodic obstacles as well as grammatical challenges to these
      children. Consequently, non-word repetition emerges as a predictor of these
      grammatical weaknesses in SLI, unlike the profile observed in typically
      developing Italian children.

PMID- 24033654
TI  - Beyond static assessment of children's receptive vocabulary: the dynamic
      assessment of word learning (DAWL).
AB  - BACKGROUND: Children's low scores on vocabulary tests are often erroneously
      interpreted as reflecting poor cognitive and/or language skills. It may be
      necessary to incorporate the measurement of word-learning ability in estimating
      children's lexical abilities. AIMS: To explore the reliability and validity of
      the Dynamic Assessment of Word Learning (DAWL), a new dynamic assessment of
      receptive vocabulary. METHODS & PROCEDURES: A dynamic assessment (DA) of word
      learning ability was developed and adopted within a nursery school setting with
      15 children aged between 3;07 and 4;03, ten of whom had been referred to speech
      and language therapy. OUTCOMES & RESULTS: A number of quantitative measures were
      derived from the DA procedure, including measures of children's ability to
      identify the targeted items and to generalize to a second exemplar, as well as
      measures of children's ability to retain the targeted items. Internal, inter
      rater and test-retest reliability of the DAWL was established as well as
      correlational measures of concurrent and predictive validity. CONCLUSIONS &
      IMPLICATIONS: The DAWL was found to provide both quantitative and qualitative
      information which could be used to improve the accuracy of differential diagnosis
      and the understanding of processes underlying the child's performance. The latter
      can be used for the purpose of designing more individualized interventions.

PMID- 24033655
TI  - Phonological therapy in jargon aphasia: effects on naming and neologisms.
AB  - BACKGROUND: Jargon aphasia is one of the most intractable forms of aphasia with
      limited recommendation on amelioration of associated naming difficulties and
      neologisms. The few naming therapy studies that exist in jargon aphasia have
      utilized either semantic or phonological approaches, but the results have been
      equivocal. Moreover, the effect of therapy on the characteristics of neologisms
      is less explored. AIMS: This study investigates the effectiveness of a
      phonological naming therapy (i.e., phonological component analysis-PCA) on
      picture-naming abilities and on quantitative and qualitative changes in
      neologisms for an individual with jargon aphasia (FF). METHODS & PROCEDURES: FF
      showed evidence of jargon aphasia with severe naming difficulties and produced a
      very high proportion of neologisms. A single-subject multiple probe design across
      behaviours was employed to evaluate the effects of PCA therapy on the accuracy
      for three sets of words. In therapy, a phonological components analysis chart was
      used to identify five phonological components (i.e. rhymes, first sound, first
      sound associate, final sound and number of syllables) for each target word.
      Generalization effects-change in per cent accuracy and error pattern-were
      examined comparing pre- and post-therapy responses on the Philadelphia Naming
      Test, and these responses were analysed to explore the characteristics of the
      neologisms. The quantitative change in neologisms was measured by change in the
      proportion of neologisms from pre- to post-therapy and the qualitative change was
      indexed by the phonological overlap between target and neologism. OUTCOMES &
      RESULTS: As a consequence of PCA therapy, FF showed a significant improvement in
      his ability to name the treated items. His performance in maintenance and follow
      up phases remained comparable with his performance during the therapy phases.
      Generalization to other naming tasks did not show a change in accuracy, but
      distinct differences in error pattern (an increase in proportion of real word
      responses and a decrease in proportion of neologisms) were observed. Notably, the
      decrease in neologisms occurred with a corresponding trend for increase in the
      phonological similarity between the neologisms and the targets. CONCLUSIONS &
      IMPLICATIONS: This study demonstrated the effectiveness of a phonological therapy
      for improving naming abilities and reducing the amount of neologisms in an
      individual with severe jargon aphasia. The positive outcome of this research is
      encouraging, as it provides evidence for effective therapies for jargon aphasia
      and also emphasizes that use of the quality and quantity of errors may provide a
      sensitive outcome measure to determine therapy effectiveness, in particular for
      client groups who are difficult to treat.

PMID- 24033657
TI  - Reduction in central H2O2 levels prevents voluntary ethanol intake in mice: a
      role for the brain catalase-H2O2 system in alcohol binge drinking.
AB  - BACKGROUND: Hydrogen peroxide (H2 O2 ) is the cosubstrate used by the enzyme
      catalase to form Compound I (the catalase-H2 O2 system), which is the major
      pathway for the conversion of ethanol (EtOH) into acetaldehyde in the brain. This
      centrally formed acetaldehyde has been shown to be involved in some of the
      psychopharmacological effects induced by EtOH in rodents, including voluntary
      alcohol intake. It has been observed that different levels of this enzyme in the
      central nervous system (CNS) result in variations in the amount of EtOH consumed.
      This has been interpreted to mean that the brain catalase-H2 O2 system, by
      determining EtOH metabolism, mediates alcohol self-administration. To date,
      however, the role of H2 O2 in voluntary EtOH drinking has not been investigated.
      METHODS: In the present study, we explored the consequence of a reduction in
      cerebral H2 O2 levels in volitional EtOH ingestion. With this end in mind, we
      injected mice of the C57BL/6J strain intraperitoneally with the H2 O2 scavengers
      alpha-lipoic acid (LA; 0 to 50 mg/kg) or ebselen (Ebs; 0 to 25 mg/kg) 15 or 60
      minutes, respectively, prior to offering them an EtOH (10%) solution following a
      drinking-in-the-dark procedure. The same procedure was followed to assess the
      selectivity of these compounds in altering EtOH intake by presenting mice with a
      (0.1%) solution of saccharin. In addition, we indirectly tested the ability of LA
      and Ebs to reduce brain H2 O2 availability. RESULTS: The results showed that both
      LA and Ebs dose-dependently reduced voluntary EtOH intake, without altering
      saccharin consumption. Moreover, we demonstrated that these treatments decreased
      the central H2 O2 levels available to catalase. CONCLUSIONS: Therefore, we
      propose that the amount of H2 O2 present in the CNS, by determining brain
      acetaldehyde formation by the catalase-H2 O2 system, could be a factor that
      determines an animal's propensity to consume EtOH.

PMID- 24033656
TI  - Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month
      outcomes.
AB  - Reduced upper airway muscle activity during sleep is a key contributor to
      obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates
      upper airway dilator muscles, including the genioglossus, and has the potential
      to reduce obstructive sleep apnea severity. The objective of this study was to
      examine the safety, feasibility and efficacy of a novel hypoglossal nerve
      stimulation system (HGNS; Apnex Medical, St Paul, MN, USA) in treating
      obstructive sleep apnea at 12 months following implantation. Thirty-one subjects
      (35% female, age 52.4 +/- 9.4 years) with moderate to severe obstructive sleep
      apnea and unable to tolerate positive airway pressure underwent surgical
      implantation and activation of the hypoglossal nerve stimulation system in a
      prospective single-arm interventional trial. Primary outcomes were changes in
      obstructive sleep apnea severity (apnea-hypopnea index, from in-laboratory
      polysomnogram) and sleep-related quality of life [Functional Outcomes of Sleep
      Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 +/- 16% of
      nights for 5.4 +/- 1.4 h per night. There was a significant improvement (P <
      0.001) from baseline to 12 months in apnea-hypopnea index (45.4 +/- 17.5 to 25.3
      +/- 20.6 events h(-1) ) and Functional Outcomes of Sleep Questionnaire score
      (14.2 +/- 2.0 to 17.0 +/- 2.4), as well as other polysomnogram and symptom
      measures. Outcomes were stable compared with 6 months following implantation.
      Three serious device-related adverse events occurred: an infection requiring
      device removal; and two stimulation lead cuff dislodgements requiring
      replacement. There were no significant adverse events with onset later than 6
      months following implantation. Hypoglossal nerve stimulation demonstrated
      favourable safety, feasibility and efficacy.

PMID- 24033658
TI  - Attitudes towards and knowledge of nutrition support amongst health care
      professionals on London intensive care units.
AB  - BACKGROUND: Nutrition support on intensive care units (ICUs) has gained a higher
      profile ever since the development of published guidelines (Clin. Nutr. 2006, 25,
      210; J. Parenter. Enteral Nutr. 2009, 33, 277;
      http://www.nice.org.uk/Guidance/CG32; Clin. Nutr. 2009, 28, 387). However, there
      are limited data available on knowledge and attitudes towards nutrition support
      specific to ICU. METHODS: An online survey was sent to all healthcare
      professionals working on ICUs across London via an e-mail link. The aim of the
      study was to assess the knowledge base of and attitudes of staff towards
      nutrition support, within an ICU setting, and to understand their educational
      needs. The results were analysed using descriptive statistics. RESULTS: Attitudes
      were in line with the evidence in current nutrition guidelines. The proportion of
      healthcare professionals who were regarded as demonstrating sufficient
      understanding of the evidence set out in the nutrition support guidelines were
      44% of clinicians, 26% of nurses, 76% of dietitians and 67% of other staff. In
      total, 59% of staff wanted more education on a number of aspects related to
      nutrition support on ICU. CONCLUSIONS: The present study highlights the need for
      more prominent dissemination of the current guidelines and illustrates the
      preferred mode. Specific gaps in knowledge regarding energy intake and the use of
      parenteral feeding are highlighted. It is hoped that the present survey will help
      to guide education in this area.

PMID- 24033659
TI  - Rates of emergency department visits due to pneumonia in the United States, July
      2006-June 2009.
AB  - OBJECTIVES: Pneumonia hospitalization rates are frequently reported as a measure
      of pneumonia disease burden in the United States. However, a detailed
      understanding of pneumonia burden in all health care settings, including the
      emergency department (ED), is essential for measuring the full effect of this
      disease on the population and planning and evaluating interventions to reduce
      pneumonia-related morbidity. The aim of this study was to quantify pneumonia
      attributable ED visits in the United States among children and adults during the
      3-year period July 2006 through June 2009. METHODS: Rates of pneumonia ED visits
      were calculated using the Nationwide Emergency Department Sample (NEDS), the
      largest source of U.S. ED data. Pneumonia ED visits were identified using
      International Classification of Diseases (ICD) codes within NEDS. A pneumonia ED
      visit was defined by a primary (first-listed) pneumonia discharge diagnosis or a
      secondary pneumonia diagnosis with an accompanying primary diagnosis of
      respiratory failure, shock, septicemia, a sign or symptom consistent with
      pneumonia, another acute respiratory infection, or an acute exacerbation of a
      chronic pulmonary disease. Population-based annual rates of pneumonia ED visits
      stratified by age group and geographic region from July 2006 through June 2009
      were calculated. The percentages of pneumonia ED visits resulting in treat-and
      release outpatient ED visits were also calculated within each age stratum.
      RESULTS: During the study period, 6,917,025 ED visits for pneumonia were
      identified, representing 2.2% of all U.S. ED visits. During the 3 study years,
      defined as July through June of 2006-2007, 2007-2008, and 2008-2009, pneumonia ED
      visit rates per 1,000 person-years were 7.4 (95% confidence interval [CI] = 7.0
      to 7.8), 7.8 (95% CI = 7.3 to 8.2), and 7.6 (95% CI = 7.1 to 8.0), respectively.
      Annual rates were stable over the 3 years within each age group and geographic
      region. Overall, 39.3% of pneumonia ED visits, including 74.5% of pediatric and
      28.1% of adult visits, were managed as treat-and-release outpatient visits.
      CONCLUSIONS: Pneumonia accounts for 2.2% of ED visits in the United States and
      results in approximately seven to eight ED visits per 1000 persons per year. A
      substantial proportion of pneumonia cases diagnosed in the ED are managed in
      treat-and-release ED outpatient visits, highlighting that enumeration of ED visit
      rates provides important complementary information to hospitalization rates for
      the assessment of pneumonia burden.

PMID- 24033660
TI  - Elevated serum IGF-I, but unaltered sex steroid levels, in healthy boys with
      pubertal gynaecomastia.
AB  - OBJECTIVE: Pubertal gynaecomastia is a very common condition. Although the
      underlying aetiology is poorly understood, it is generally accepted that excess
      of oestrogens and deficit of androgens are involved in the pathogenesis.
      Furthermore, adiposity as well as the GH/IGF-I axis may play a role. In this
      study, we elucidate the association of adiposity and levels of follicle
      stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin
      (SHBG), testosterone, oestrogen, IGF-I and IGFBP-3 with the presence of pubertal
      gynaecomastia in a large cohort of healthy boys. PATIENTS: A total of 501 healthy
      Danish school boys (aged 6.1-19.8 year) from the COPENHAGEN Puberty Study.
      MEASUREMENTS: Anthropometry and pubertal stages (PH1-6 and G1-5) were evaluated,
      and the presence of gynaecomastia was assessed. Body fat percentage was
      calculated by means of four skin folds and impedance. Nonfasting blood samples
      were analysed for FSH, LH, testosterone, SHBG, oestradiol, IGF-I, IGFBP-3 and
      prolactin. RESULTS: We found that 23% (31/133) of all pubertal boys had
      gynaecomastia. More specifically, 63% (10/16) of boys in genital stage 4 had
      gynaecomastia. Boys with gynaecomastia had significantly higher IGF-I levels
      compared with controls (IGF-I SD-score 0.72 vs -0.037, P < 0.001). This
      difference was maintained after adjusting for confounders (age and pubertal
      stage). Sex steroid levels, oestradiol/testosterone ratio or free testosterone
      were not associated with the presence of gynaecomastia with or without adjustment
      for confounders. CONCLUSIONS: IGF-I levels were elevated in healthy boys with
      pubertal gynaecomastia compared with boys without gynaecomastia, whereas sex
      steroid levels did not differ. We speculate that the GH-IGF-I axis may be
      involved in the pathogenesis of pubertal gynaecomastia.

PMID- 24033661
TI  - Humoral hypercalcemia caused by uterine corpus carcinosarcoma consisting of
      squamous cell carcinoma in its epithelial component.
AB  - Humoral hypercalcemia of malignancy (HHM) is a paraneoplastic syndrome primarily
      caused by a tumor-producing parathyroid hormone-related protein (PTH-rP). We
      describe the first reported case of a uterine carcinosarcoma causing HHM. A 70
      year-old patient was transferred to our hospital for a uterine tumor accompanied
      by impaired consciousness. The laboratory tests indicated anemia, malnutrition,
      elevated serum calcium and elevated PTH-rP. Emergency surgery, including
      abdominal hysterectomy and bilateral salpingo-oophorectomy, was performed due to
      uncontrollable uterine bleeding. The pathological diagnosis was carcinosarcoma
      consisting of pure squamous cell carcinoma in its epithelial component.
      Postoperatively, chemotherapy with paclitaxel and carboplatin was performed. The
      patient had recurrent tumors at the para-aortic lymph nodes 11 months after the
      initial surgery and underwent a pelvic and para-aortic lymphadenectomy, which
      removed all of the recurrent tumors. 

PMID- 24033662
TI  - Legal substance use and the development of a DSM-IV cannabis use disorder during
      adolescence: the TRAILS study.
AB  - AIMS: To examine whether early onset of tobacco or alcohol use, and continued use
      of tobacco or alcohol in early adolescence, are related to a higher likelihood of
      developing a cannabis use disorder during adolescence. DESIGN AND SETTING: Data
      were used from four consecutive assessment waves of the TRacking Adolescents'
      Individual Lives Survey (TRAILS), a general Dutch population study. TRAILS is an
      ongoing longitudinal study that will follow the same group of adolescents from
      the ages of 10 to 24 years. PARTICIPANTS: The sample consisted of 1108 (58%
      female) adolescents (mean ages at the four assessment waves are 11.09, 13.56,
      16.27 and 19.05 years, respectively) MEASUREMENTS: Cannabis use disorders were
      assessed using the Composite International Diagnostic Interview 3.0 (CIDI).
      Adolescent tobacco and alcohol use were assessed using self-report
      questionnaires. FINDINGS: Early-onset tobacco use [odds ratio (OR) = 1.82,
      confidence interval (CI) = 1.05-3.14, P < 0.05], but not early-onset alcohol use
      (OR = 1.33, CI = 0.84-2.12, P > 0.05), was associated with a higher likelihood of
      developing a cannabis use disorder. Similarly, adolescents who reported continued
      use of tobacco (OR = 2.47, CI = 1.02-5.98, P < 0.05), but not continued use of
      alcohol (OR = 1.71, CI = 0.87-3.38, P > 0.05), were more likely to develop a
      cannabis use disorder. CONCLUSIONS: Early-onset and continued tobacco use appear
      to predict the development of a cannabis use disorder in adolescence, whereas
      early onset and continued alcohol use do not.

PMID- 24033663
TI  - Risks to children and young adults.

PMID- 24033664
TI  - Cyproheptadine-induced myeloma cell apoptosis is associated with inhibition of
      the PI3K/AKT signaling.
AB  - Recent studies revealed that the anti-allergic cyproheptadine displays anti-blood
      cancer activity. However, its mechanism is still elusive. In this study,
      cyproheptadine was found to decrease the expression of anti-apoptotic proteins,
      including Bcl-2, Mcl-1, and XIAP. More importantly, cyproheptadine-induced
      apoptosis was accompanied by suppressing AKT activation in myeloma cells. In the
      subsequent study, cyproheptadine was found to inhibit insulin-like growth factor
      1-triggered AKT activation in a time- and concentration-dependent manner.
      Specifically, cyproheptadine blocked AKT translocation from nuclei for
      phosphorylation. This inhibition led to suppressed activation of p70S6K and
      4EBP1, two key downstream signaling proteins in the PI3K/AKT pathway. However,
      cyproheptadine did not display inhibition on activation of IGF-1R or STAT3,
      possible upstream signals of AKT activation. These results further demonstrated
      that cyproheptadine suppresses the PI3K/AKT signaling pathway, which is probably
      critical for cyproheptadine-induced MM cell apoptosis. 

PMID- 24033665
TI  - The effect of an oral probiotic containing lactobacillus, bifidobacterium, and
      bacillus species on the vaginal microbiota of spayed female dogs.
AB  - BACKGROUND: Recurrent urinary tract infections (UTIs) are often difficult to
      treat. Vaginal colonization with lactic acid-producing bacteria (LAB) is
      associated with reduced frequency of recurrent UTIs in women. Oral probiotics
      might help increase the prevalence of vaginal LAB and decrease the frequency of
      recurrent UTIs in dogs. HYPOTHESIS: Administration of an oral probiotic
      supplement containing Lactobacillus, Bifidobacterium, and Bacillus species will
      increase the prevalence of LAB in the vagina of dogs. ANIMALS: Thirty-five
      healthy, spayed female dogs without history of recurrent UTIs. METHODS:
      Prospective, controlled study. Enrolled dogs received an oral probiotic
      supplement for 14 or 28 days. A vaginal tract culture was obtained from each dog
      before and after oral probiotic administration. Twenty-three dogs received the
      oral probiotic supplement daily for a period of 14 days and 12 dogs received the
      oral probiotic supplement daily for a period of 28 days. RESULTS: Lactic acid
      producing bacteria were isolated from 7 of 35 dogs prior to probiotic
      administration. After the treatment course, 6 of 35 dogs had LAB isolated. Only
      one of these dogs had LAB (Enterococcus canintestini) isolated for the first
      time. Enterococcus canintestini was the most common LAB isolated from all dogs in
      this study, although it was not included in the probiotic supplement. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Lactic acid-producing bacteria are not a common isolate
      from the vaginal vault of dogs. Administration of this oral probiotic supplement
      for a 2- or 4-week period did not increase the prevalence of vaginal LAB in dogs.

PMID- 24033666
TI  - Metabolic tumor volume by positron emission tomography/computed tomography as a
      clinical parameter to determine therapeutic modality for early stage Hodgkin's
      lymphoma.
AB  - Recent studies have shown that metabolic tumor volume (MTV) by positron emission
      tomography/computed tomography (PET/CT) is an important prognostic parameter in
      patients with non-Hodgkin's lymphoma. However, it is unknown whether doxorubicin,
      bleomycin, vinblastine, dacarbazine (ABVD) alone in early stage Hodgkin's
      lymphoma would lead to similar disease control as combined modality therapy (CMT)
      using MTV by PET/CT. One hundred and twenty-seven patients with early stage
      Hodgkin's lymphoma who underwent PET/CT at diagnosis were enrolled. The MTV was
      delineated on PET/CT by the area >=SUV(max), 2.5 (standardized uptake value
      [SUV]). Sixty-six patients received six cycles of ABVD only. The other 61
      patients received CMT (involved-field radiotherapy after 4-6 cycles of ABVD). The
      calculated MTV cut-off value was 198 cm(3) . Clinical outcomes were compared
      according to several prognostic factors (i.e. age >=50 years, male, performance
      status >=2, stage II, B symptoms, >=4 involved sites, extranodal site, large
      mediastinal mass, CMT, elevated erythrocyte sedimentation rate and high MTV).
      Older age (progression-free survival [PFS], P = 0.003; overall survival [OS], P =
      0.007), B symptoms (PFS, P = 0.006; OS, P = 0.036) and high MTV (PFS, P = 0.008;
      OS, P = 0.007) were significant independent prognostic factors. Survival of two
      high MTV groups treated with ABVD only and CMT were lower than the low MTV groups
      (PFS, P < 0.012; OS, P < 0.045). ABVD alone was sufficient to control disease in
      those with low MTV status. However, survival was poor, even if the CMT was
      assigned a high MTV status. The MTV would be helpful for deciding the therapeutic
      modality in patients with early stage Hodgkin's lymphoma.

PMID- 24033667
TI  - Detection of Cryptosporidium and Giardia in clinical laboratories in Europe--a
      comparative study.
AB  - To determine the routine diagnostic methods used and compare the performance in
      detection of oocysts of Cryptosporidium species and cysts of Giardia intestinalis
      in faecal samples by European specialist parasitology laboratories and European
      clinical laboratories. Two sets of seven formalin-preserved faecal samples, one
      containing cysts of Giardia intestinalis and the other, containing oocysts of
      Cryptosporidium, were sent to 18 laboratories. Participants were asked to examine
      the specimens using their routine protocol for detecting these parasites and
      state the method(s) used. Eighteen laboratories answered the questionnaire. For
      detection of Giardia, 16 of them used sedimentation/concentration followed by
      light microscopy. Using this technique the lower limit of detection of Giardia
      was 17.2 cysts/mL of faeces in the best performing laboratories. Only three of 16
      laboratories used fluorescent-conjugated antibody-based microscopy. For detection
      of Cryptosporidium acid-fast staining was used by 14 of the 17 laboratories that
      examined the samples. With this technique the lower limit of detection was 976
      oocysts/mL of faeces. Fluorescent-conjugated antibody-based microscopy was used
      by only five of the 17 laboratories. There was variation in the lower limit of
      detection of cysts of Giardia and oocysts of Cryptosporidium between laboratories
      using the same basic microscopic methods. Fluorescent-conjugated antibody-based
      microscopy was not superior to light microscopy under the conditions of this
      study. There is a need for a larger-scale multi-site comparison of the methods
      used for the diagnosis of these parasites and the development of a Europe-wide
      laboratory protocol based upon its findings.

PMID- 24033668
TI  - Real evaporative cooling efficiency of one-layer tight-fitting sportswear in a
      hot environment.
AB  - Real evaporative cooling efficiency, the ratio of real evaporative heat loss to
      evaporative cooling potential, is an important parameter to characterize the real
      cooling benefit for the human body. Previous studies on protective clothing
      showed that the cooling efficiency decreases with increasing distance between the
      evaporation locations and the human skin. However, it is still unclear how
      evaporative cooling efficiency decreases as the moisture is transported from the
      skin to the clothing layer. In this study, we performed experiments with a
      sweating torso manikin to mimic three different phases of moisture absorption in
      one-layer tight-fitting sportswear. Clothing materials Coolmax((r)) (CM; INVISTA,
      Wichita, Kansas, USA; 100%, profiled cross-section polyester fiber), merino wool
      (MW; 100%), sports wool (SW; 50% wool, 50% polyester), and cotton (CO; 100%) were
      selected for the study. The results demonstrated that, for the sportswear
      materials tested, the real evaporative cooling efficiency linearly decreases with
      the increasing ratio of moisture being transported away from skin surface to
      clothing layer (adjusted R(2) >0.97). In addition, clothing fabric thickness has
      a negative effect on the real evaporative cooling efficiency. Clothing CM and SW
      showed a good ability in maintaining evaporative cooling efficiency. In contrast,
      clothing MW made from thicker fabric had the worst performance in maintaining
      evaporative cooling efficiency. It is thus suggested that thin fabric materials
      such as CM and SW should be used to manufacture one-layer tight-fitting
      sportswear. 

PMID- 24033669
TI  - Comparison of the biomechanical properties of a ventral cervical intervertebral
      anchored fusion device with locking plate fixation applied to cadaveric canine
      cervical spines.
AB  - OBJECTIVE: To evaluate fixation properties of a new intervertebral anchored
      fusion device and compare these with ventral locking plate fixation. STUDY
      DESIGN: In vitro biomechanical evaluation. ANIMALS: Cadaveric canine C4-C7
      cervical spines (n = 9). METHODS: Cervical spines were nondestructively loaded
      with pure moments in a nonconstraining testing apparatus to induce
      flexion/extension while angular motion was measured. Range of motion (ROM) and
      neutral zone (NZ) were calculated for (1) intact specimens, (2) specimens after
      discectomy and fixation with a purpose-built intervertebral fusion cage with
      integrated ventral fixation, and (3) after removal of the device and fixation
      with a ventral locking plate. RESULTS: Both fixation techniques resulted in a
      decrease in ROM and NZ (P < .001) compared with the intact segments. There were
      no significant differences between the anchored spacer and locking plate
      fixation. CONCLUSION: An anchored spacer appears to provide similar biomechanical
      stability to that of locking plate fixation.

PMID- 24033673
TI  - Abstracts of the Royal Pharmaceutical Society (RPS) Annual Conference 2013.
      September 8-9, 2013. Birmingham, United Kingdom.

PMID- 24033670
TI  - CYP2D6 variation, behaviour and psychopathology: implications for
      pharmacogenomics-guided clinical trials.
AB  - Individual and population differences in polymorphic cytochrome P450 enzyme
      function have been known for decades. The biological significance of these
      differences has now been deciphered with regard to drug metabolism, action and
      toxicity as well as disposition of endogenous substrates, including neuroactive
      compounds. While the cytochrome P450 enzymes occur abundantly in the liver, they
      are expressed in most tissues of the body, albeit in varying amounts, including
      the brain. The latter location of cytochrome P450s is highly pertinent for
      susceptibility to neuropsychiatric diseases, not to mention local drug metabolism
      at the site of psychotropic drug action in the brain. In the current era of
      personality medicine with companion theranostics (i.e. the fusion of therapeutics
      with diagnostics), this article underscores that such versatile biological roles
      of cytochrome P450s offer multiple points of entry for personalized medicine and
      rational therapeutics. We focus our discussion on CYP2D6, one of the most
      intensively researched drug and endogenous compound metabolism pathways, with a
      view to relevance for, and optimization of, pharmacogenomic-guided clinical
      trials. Working on the premise that CYP2D6 is related to human behaviour and
      certain personality traits such as serotonin and dopamine system function, we
      further suggest that the motivation of healthy volunteers to participate in
      clinical trials may in part be influenced by an under- or over-representation of
      certain CYP2D6 metabolic groups. 

PMID- 24033674
TI  - Editorial comment from Dr Schiavina et al. to Standardized assessment of
      complications in a contemporary series of European patients undergoing radical
      cystectomy.

PMID- 24033675
TI  - Assessing risk and guidance on monitoring of Batrachochytrium dendrobatidis in
      Europe through identification of taxonomic selectivity of infection.
AB  - Amphibians are globally threatened, but not all species are affected equally by
      different threatening processes. This is true for the threat posed by the
      chytridiomycete fungus (Batrachochytrium dendrobatidis). We compiled a European
      data set for B. dendrobatidis to analyze the trends of infection in European
      amphibians. The risk of infection was not randomly distributed geographically or
      taxonomically across Europe. Within countries with different prevalence,
      infection was nonrandom in certain amphibian taxa. Brown frogs of the genus Rana
      were unlikely to be infected, whereas frogs in the families Alytidae and
      Bombinatoridae were significantly more likely to be infected than predicted by
      chance. Frogs in the 2 families susceptible to B. dendrobatidis should form the
      core of attempts to develop spatial surveillance studies of chytridiomycosis in
      Europe. Ideally, surveys for B. dendrobatidis should be augmented by sampling the
      widespread genus Pelophylax because this taxon exhibits geographically
      inconsistent overinfection with B. dendrobatidis and surveillance of it may
      facilitate recognition of factors causing spatial variability of infection
      intensity. Several European amphibian taxa were not represented in our data set;
      however, surveillance of unsampled species should also occur when warranted.

PMID- 24033676
TI  - Early predictive value of susceptibility weighted imaging (SWI) in pediatric
      hypoxic-ischemic injury.
AB  - Susceptibility weighted imaging (SWI) provides information about the
      intravascular cerebral blood oxygenation level. Deoxyhemoglobin is increased in
      tissue with increased oxygen extraction fraction. Accordingly, the draining veins
      in hypoxic-ischemic brain may reveal abnormally low SWI signal. We report on a
      boy with hypoxic-ischemic injury (HII) after cardiac arrest and the ability of
      SWI to depict areas of HII by focusing on the venous cerebral drainage. 

PMID- 24033678
TI  - Masson tumor arising in a congenital vascular anomaly.
AB  - Congenital and infantile Masson's tumors are rare. We report a case of Masson's
      tumors arising within a congenital vascular mass in an otherwise healthy infant.
      The diagnosis was made following surgical excision and supported by histologic
      staining. There has been no recurrence of the lesions to date. 

PMID- 24033677
TI  - Childhood verbal development and drinking behaviors from adolescence to young
      adulthood: a discordant twin-pair analysis.
AB  - BACKGROUND: Studies suggest that better cognitive and verbal abilities in
      childhood predict earlier experimentation with alcohol and higher levels of
      drinking in adolescence, whereas poorer ability is related to a higher likelihood
      of remaining abstinent. Whether individual differences in language development in
      childhood predict differences in adolescent drinking behaviors has not been
      studied. METHODS: To address that question, we compared co-twins from twin pairs
      discordant for their childhood language development and studied associations of
      parental reports of within-pair differences in age at speaking words, age at
      learning to read, and expressive language skills during school age with self
      reported within-pair differences in drinking, intoxication, and alcohol-related
      problems across adolescence and young adulthood. Data from 2 longitudinal
      population-based samples of twin families were used, with verbal developmental
      differences in childhood reported by the parents when the twins were 12 and 16
      years of age, respectively. RESULTS: Conditional logistic regression analyses and
      within-pair correlation analyses suggested positive associations between verbal
      development and drinking behaviors in both data sets. In analyses adjusted for
      birth order and birth weight, the co-twin reported to be verbally more advanced
      in childhood tended to report more frequent drinking and intoxication in
      adolescence in both samples. Better verbal development also was associated with
      the likelihood of having friends who drink in adolescence. CONCLUSIONS: These
      findings suggest that, adjusting for familial and other factors shared by co
      twins, better verbal development in childhood predicts more frequent drinking and
      intoxication in adolescence and young adulthood, possibly due, in part, to peer
      associations.

PMID- 24033679
TI  - Enterobius vermicularis: Can it be a possible pathogen in Bartholin gland abscess
      formation?
AB  - The most frequent disorders of the Bartholin glands are cysts or abscesses.
      Bartholin gland abscesses occur generally as a result of polymicrobial infections
      or agents that cause sexually transmitted diseases. But as far as we know, no
      parasite has been previously reported among the infectious agents that are
      detected from the abscesses of the Bartholin gland. Here, we report a 45-year-old
      woman, in the Bartholin abscess aspirate of whom Enterobius vermicularis eggs
      were detected in between the inflammatory infiltrate by cytological examination. 

PMID- 24033680
TI  - Meeting challenges related to the dietary assessment of ethnic minority
      populations.
AB  - BACKGROUND: Migrants from the Indian subcontinent comprise the largest minority
      group in the UK. With the process of migration come alterations in lifestyle and
      eating habits. The present study aimed to disseminate the valuable information,
      experiences and challenges faced by researchers who conduct studies with ethnic
      minority groups in the area of diet and nutritional surveys, with an emphasis on
      migrant South Asians. METHODS: The findings reported are the result of research
      carried out during 2008-2012, involving 1100 face-to-face dietary recalls
      conducted in the UK among South Asian children (aged 1.5-11 years; n = 300) and
      adults (>=30 years; n = 100). RESULTS: Factors to consider when planning and
      carrying out diet and nutrition survey studies among migrant South Asians were
      identified and include the employment of culture-specific tools, visual aid
      reinforcement and the involvement of key community members and translators to
      facilitate recruitment and data collection. One of the best practices found when
      working with minority groups was the use of incentives and tangible benefits to
      reward study participants. It was also found that constant communication and
      follow-up of the study participants improved the quality of the data and the
      likelihood of maintaining links with community members for future studies.
      CONCLUSIONS: From the results of in-house studies and a revision of practices
      reported in earlier literature, two 24-h face-to-face dietary recalls are
      recommended as the optimal method for the dietary assessment of migrant South
      Asians. To complement this assessment, ethnic-specific food frequency
      questionnaires such as that developed and successfully implemented among South
      Asians in the present study must be employed.

PMID- 24033681
TI  - Sleep and cardiovascular phenotype in middle-aged hypocretin-deficient
      narcoleptic mice.
AB  - Narcolepsy with cataplexy (NC) is a lifelong disorder caused by loss of
      hypothalamic hypocretin/orexin (HCRT) neurones, often starting in childhood. NC
      patients show altered control of heart rate (HR) and a normotensive non-dipper
      blood pressure (BP) profile, but the natural history and prognostic significance
      of these alterations remain unclear. Similar alterations have been observed in
      HCRT-ataxin-3 transgenic (TG) NC mice lacking HCRT neurones, but studies have
      been limited to young adult individuals <4 months of age. Here we evaluated long
      term effects of NC on derangements in the wake-sleep state and cardiovascular
      control by studying middle-aged TG. We chronically instrumented TG and wild-type
      mice aged 10-11 months with electrodes for sleep scoring and a telemetric
      transducer for BP and HR measurements. We then recorded mice in freely behaving
      conditions. TG showed a NC phenotype including fragmentation of wakefulness,
      reduced latency to rapid eye movement sleep (REMS) and cataplexy-like events. TG
      also showed blunted BP decline on entering non-rapid eye movement sleep (NREMS),
      enhanced BP increase on passing to REMS, increased HR, and blunted changes in HR
      upon arousal and awakening from NREMS. Histological and ultrastructural analysis
      of cardiovascular and renal tissue did not reveal evidence of subclinical
      hypertensive organ damage. These data indicate that HCRT neurone loss in TG
      causes alterations in wake-sleep behaviour and cardiovascular control that are
      not peculiar to the beginning of the disease but are maintained at least up to
      middle age. These alterations are similar to those in adult NC patients, but do
      not produce early subclinical damage to the heart and kidneys. 

PMID- 24033684
TI  - Diagnostic accuracy of fingerstick beta-hydroxybutyrate for ketonuria in pregnant
      women with nausea and vomiting.
AB  - OBJECTIVES: The aim of this study was to determine whether a rapid, fingerstick
      beta-hydroxybutyrate (beta-OHB) test predicts ketonuria in pregnant women with
      nausea and vomiting. METHODS: A convenience sample of 82 pregnant women who
      presented to the Barnes-Jewish Hospital emergency department (ED) with complaints
      of nausea or vomiting were enrolled into an institutional review board-approved,
      prospective, observational study. Exclusion criteria were temperature of >38.3
      degrees C, altered mental status, prisoners, and >1 L of any intravenous (IV)
      fluid before screening. Subjects had fingerstick beta-OHB tests, with results
      reported in increments of 0.1 mmol/L. Urine ketone results were made available
      once reported as part of standard care and varied from 0 (trace) to +4 values.
      Ketonuria was defined as a urine ketone value of 3+ or 4+ and was analyzed as a
      dichotomous, categorical variable. A contingency table and receiver operator
      characteristic (ROC) curve were constructed for comparing the beta-OHB values to
      those urine ketone values for each patient. RESULTS: Mean (+/-SD) beta-OHB was
      0.43 (+/-0.52) mmol/L, and median urine was 1+ for the cohort as a whole. The
      area under the ROC curve equaled 0.95. The sensitivity and specificity for a
      fingerstick test of >0.45 mmol/L were 89 and 94.5%, respectively. The positive
      likelihood ratio (LR) was 16, and the negative LR was 0.12. CONCLUSIONS:
      Fingerstick beta-OHB is a rapid and reliable diagnostic tool that correlates well
      with ketonuria and identifies ketonemia in pregnant women with nausea and
      vomiting. Fingerstick beta-OHB testing has the potential to increase triage
      efficiency, shorten length-of-stay times, and positively affect patient outcomes
      in an ED setting.

PMID- 24033683
TI  - Effects of high-fat and high-carbohydrate diets on fat and carbohydrate oxidation
      and plasma metabolites in healthy cats.
AB  - High-fat (HF) or high-carbohydrate (HC) diets (30% fat, 18.9% carbohydrate; HF
      and 10% fat, 46.3% carbohydrate; HC) and lengths of adaptation were investigated
      in cats (Felis catus; 10 +/- 2 months, 3.6 +/- 0.3 kg). Cats randomly received
      each treatment for 14 days in a crossover design with a 14-day washout period
      between each diet. Three 22-h indirect calorimetry studies were conducted after
      acute (day 0), semichronic (day 4) and chronic (day 13) dietary exposure. Blood
      samples were collected after a 24-h fast on days 1, 5 and 14. When cats consumed
      the HC and HF diet, oxidation of the restricted nutrient exceeded intake while
      oxidation of the nutrient in excess matched intake. Mean max energy expenditure
      (EE) of cats consuming the HF and HC diet were 107 and 102 kcal/kg(0.67)/day and
      occurred at a mean of 4 and 12 h post-feeding respectively. Maximal fat (0.90
      g/h) and carbohydrate (carbohydrate; 1.42 g/h) oxidation were attained at 26 min
      and 10.4 h post-feeding respectively. The changes observed in macronutrient
      oxidation and EE suggest that cats adapt whole-body nutrient metabolism in
      response to changes in dietary macronutrient content, but may require longer than
      14 day to adapt to a macronutrient that is present at a lower concentration in
      the diet.

PMID- 24033682
TI  - Chronic alcohol ingestion primes the lung for bleomycin-induced fibrosis in mice.
AB  - BACKGROUND: Alcohol abuse increases the risk for acute lung injury (ALI). In both
      experimental models and in clinical studies, chronic alcohol ingestion causes
      airway oxidative stress and glutathione depletion and increases the expression of
      transforming growth factor beta-1 (TGFbeta1), a potent inducer of fibrosis, in
      the lung. Therefore, we hypothesized that alcohol ingestion could promote
      aberrant fibrosis following experimental ALI and that treatment with the
      glutathione precursor s-adenosylmethionine (SAMe) could mitigate these effects.
      METHODS: Three-month-old C57BL/6 mice were fed standard chow +/- alcohol (20%
      v/v) in their drinking water for 8 weeks and +/-SAMe (4% w/v) during the last 4
      weeks. ALI was induced by intratracheal instillation of bleomycin (2.5 units/kg),
      and lungs were assessed histologically at 7 and 14 days for fibrosis and at 14
      days for the expression of extracellular matrix proteins and TGFbeta1. RESULTS:
      Alcohol ingestion had no apparent effect on lung inflammation at 7 days, but at
      14 days after bleomycin treatment, it increased lung tissue collagen deposition,
      hydroxyproline content, and the release of activated TGFbeta1 into the airway. In
      contrast, SAMe supplementation completely mitigated alcohol-induced priming of
      these aberrant fibrotic changes through decreased TGFbeta1 expression in the
      lung. In parallel, SAMe decreased alcohol-induced TGFbeta1 and Smad3 mRNA
      expressions by lung fibroblasts in vitro. CONCLUSIONS: These new experimental
      findings demonstrate that chronic alcohol ingestion renders the experimental
      mouse lung susceptible to fibrosis following bleomycin-induced ALI, and that
      these effects are likely driven by alcohol-mediated oxidative stress and its
      induction and activation of TGFbeta1.

PMID- 24033685
TI  - How mothers interact with children with suspected cow's milk allergy symptoms.
AB  - AIM: To characterize mother-child interaction in children with suspected
      gastrointestinally manifested cow's milk allergy (GI-CMA) and to explore factors
      associated with the parentally perceived symptoms. METHODS: We invited a randomly
      selected group of children with suspected GI-CMA and their mothers to take part
      in a video recording of them playing together. The mother-child interaction was
      rated using the Emotional Availability Scales (EAS, 4th edition) and compared
      with national normative data. RESULTS: Video recordings were conducted with 24
      patients (15 girls and nine boys) with a median age of 10.1 months (range 2.1
      20.5 months) undergoing a double-blind, placebo-controlled food challenge for
      cow's milk allergy. The EAS profile in the challenge negative group (17/24) was
      significantly different from the normative data. The scores for maternal
      sensitivity (p = 0.0049) and nonintrusiveness (p = 0.0192), together with child
      responsiveness (p = 0.0053) and involvement of mother (p = 0.0085), were all
      significantly lower when compared to the normative data. The dimensions of
      maternal nonhostility and structuring, as well as the scores of the challenge
      positive group, did not differ from the normative data. CONCLUSION: Dysfunctional
      mother-child emotional interaction was frequent in young children with suspected
      GI-CMA ruled out by the cow's milk challenge. Appropriate psychological support
      should be considered.

PMID- 24033686
TI  - Uncertainty importance analysis using parametric moment ratio functions.
AB  - This article presents a new importance analysis framework, called parametric
      moment ratio function, for measuring the reduction of model output uncertainty
      when the distribution parameters of inputs are changed, and the emphasis is put
      on the mean and variance ratio functions with respect to the variances of model
      inputs. The proposed concepts efficiently guide the analyst to achieve a targeted
      reduction on the model output mean and variance by operating on the variances of
      model inputs. The unbiased and progressive unbiased Monte Carlo estimators are
      also derived for the parametric mean and variance ratio functions, respectively.
      Only a set of samples is needed for implementing the proposed importance analysis
      by the proposed estimators, thus the computational cost is free of input
      dimensionality. An analytical test example with highly nonlinear behavior is
      introduced for illustrating the engineering significance of the proposed
      importance analysis technique and verifying the efficiency and convergence of the
      derived Monte Carlo estimators. Finally, the moment ratio function is applied to
      a planar 10-bar structure for achieving a targeted 50% reduction of the model
      output variance. 

PMID- 24033687
TI  - Long-term prognosis of childhood acute promyelocytic leukaemia with arsenic
      trioxide administration in induction and consolidation chemotherapy phases: a
      single-centre experience.
AB  - OBJECTIVES: The efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide
      (As2 O3 ) as induction therapy for adult acute promyelocytic leukaemia (APL) has
      been documented in several clinical trials. However, the role of ATRA/As2 O3
      combination in induction and consolidation therapy in children remains unclear.
      Here, we report the efficacy of combined treatment with As2 O3 and ATRA as
      induction and consolidation chemotherapy to treat newly diagnosed childhood APL.
      METHODS: From 1998 to 2011, 43 children with newly diagnosed APL received
      induction and consolidation chemotherapy with ATRA and As2 O3 (Protocol B). Rates
      of complete remission (CR), event-free survival (EFS), disease-free survival
      (DFS), and overall survival (OS) and drug toxicity were compared between children
      treated with Protocol B and 25 others treated previously with ATRA alone as
      induction chemotherapy (Protocol A). RESULTS: Of 43 patients treated with
      Protocol B, 41 (95.4%) achieved CR (two died of intracranial haemorrhage on day
      10 and 14). In contrast, only 20 (80%) of 25 patients treated with Protocol A
      achieved CR. Thus, the CR rate was significantly lower in patients receiving
      induction chemotherapy with Protocol A than in those treated with Protocol B (P =
      0.045, chi(2) = 6.508). Of the 41 patients who achieved CR on induction therapy
      with Protocol B, 40 also received consolidation therapy. Molecular relapse, but
      no overt morphological relapse, occurred in one patient at 25 months after
      diagnosis; this patient regained CR status with As2 O3 treatment. With a median
      follow-up period of 75 months, estimated EFS, DFS and OS rates were 92.5 +/-
      4.2%, 97.1 +/- 2.9% and 95.3 +/- 3.2%, respectively, for Protocol B. In contrast,
      with a median follow-up of 127 months, the EFS, DFS and OS rates at 75 months
      were 70.4 +/- 9.4%, 76.4 +/- 9.2% and 70.4 +/- 9.4%, respectively, for Protocol
      A. Thus, patients treated with Protocol A showed significantly lower EFS (P =
      0.021) and OS (P = 0.007) rates than those treated with Protocol B. CONCLUSIONS:
      Application of As2 O3 and ATRA as induction and consolidation chemotherapy
      resulted in excellent outcomes and improved long-term prognosis in children with
      newly diagnosed APL.

PMID- 24033688
TI  - A 1-year prospective analysis of injuries in amateur and elite fistball.
AB  - The purpose of this study was to examine the incidence and mechanisms of acute
      injuries in the sport of fistball. No scientific studies on injury
      characteristics have yet been conducted in this traditional sport game. The study
      was conducted prospectively over the course of 12 months. During a total of
      40.308 h of sport-specific exposure, 240 players reported 492 injuries,
      representing an overall injury rate of 12.2 injuries/1000 h of exposure. Most
      injuries were classified as bagatelle injuries (67.8%). The majority of the
      injuries were located in the knee (23.5%) followed by the elbow (11.9%) and the
      hip (11.5%). Ankle injuries resulted in the longest impairment from sports
      participation. The most common types of injury were abrasions (38.2%), contusions
      (21.1%), distortions (7.5%) and muscle strains (6.9%). Wrong or insufficient
      equipment (15.0%) was the most commonly mentioned causes of injury. The data
      indicate that the injury risk in fistball is rather high; however, the sport
      should not be considered a high-risk sport because most of the injuries are
      slight and do not prevent the players from training or competition. Injury
      prevention strategies should include the development of fistball-specific
      protective equipment with focus on the knee and elbow joint.

PMID- 24033689
TI  - CT scan based determination of optimal bone corridor for atlantoaxial ventral
      screw fixation in miniature breed dogs.
AB  - OBJECTIVE: To describe the most reliable insertion angle, corridor length and
      width to place a ventral transarticular atlantoaxial screw in miniature breed
      dogs. STUDY DESIGN: Retrospective CT imaging study. SAMPLE POPULATION: Cervical
      CT scans of toy breed dogs (n = 21). METHODS: Dogs were divided into 2 groups-
      group 1: no atlantoaxial abnormalities; group 2: atlantoaxial instability.
      Insertion angle in medial to lateral and ventral to dorsal direction was measured
      in group 1. Corridor length and width were measured in groups 1 and 2. Corridor
      width was measured at 3 points of the corridor. Each variable was measured 3
      times and the mean used for statistical analysis. RESULTS: Mean +/- SD optimal
      transarticular atlantoaxial insertion angle was determined to be 40 +/- 1 degrees
      in medial to lateral direction from the midline and 20 +/- 1 degrees  in ventral
      to dorsal direction from the floor of the neural canal of C2. Mean corridor
      length was 7 mm (range, 4.5-8.0 mm). Significant correlation was found between
      corridor length, body weight, and age. Mean bone corridor width ranged from 3 to
      5 mm. Statistically significant differences were found between individuals,
      gender and measured side. CONCLUSIONS: Optimal placement of a transarticular
      screw for atlantoaxial joint stabilization is very demanding because the screw
      path corridor is very narrow.

PMID- 24033690
TI  - Australian caregivers' management of childhood ailments.
AB  - AIM: To profile medication dosing behaviour of caregivers of children aged 5
      years and under in fever and cough/cold management. METHODS: Caregivers (n = 97),
      recruited from childcare centres in Sydney, Australia, were presented two
      scenarios in a face to face consultation with the researcher, requiring them to
      make decisions about the management of a child, including medicine dosing.
      Accuracy of doses and appropriateness of management were documented. Focus groups
      explored factors surrounding caregivers' skills. RESULTS: In the fever scenario,
      45% (44/97) chose to medicate when temperature was below 38 degrees C. Many
      measured incorrect doses and stated inappropriate dosage intervals. Only 23%
      managed the scenario appropriately. In the cough/cold scenario, 43% (38/89) chose
      to medicate. Overall, only 35% (45/127) of dose measurements observed were
      accurate based on the child's weight. Focus groups revealed that caregivers are
      not aware of risks associated with children's medicines and when to medicate.
      CONCLUSIONS: The ability of caregivers to accurately measure and administer doses
      is important. Determining the motivations to use medicines, as well as dosing
      behaviours is necessary to improve the quality use of medicines.

PMID- 24033691
TI  - Fighting drug-resistant Plasmodium falciparum: the challenge of artemisinin
      resistance.
AB  - Following a decade-long scale up of malaria control through vector control
      interventions, the introduction of rapid diagnostic tests and highly efficacious
      Artemisinin-based Combination Therapy (ACT) along with other measures, global
      malaria incidence declined significantly. The recent development of artemisinin
      resistance on the Cambodia-Thailand border, however, is of great concern. This
      review encompasses the background of artemisinin resistance in Plasmodium
      falciparum, its situation, especially in the Greater Mekong Sub-region (GMS), and
      the responses taken to overcome this resistance. The difficulties in defining
      resistance are presented, particularly the necessity of measuring the clinical
      response to artemisinins using the slow parasite-clearance phenotype. Efforts to
      understand the molecular basis of artemisinin resistance and the search for
      molecular markers are reviewed. The markers, once identified, can be applied as
      an efficient tool for resistance surveillance. Despite the limitation of current
      surveillance methods, it is important to continue vigilance for artemisinin
      resistance. The therapeutic efficacy "in vivo study" network for monitoring
      antimalarial resistance in the GMS has been strengthened. GMS countries are
      working together in response to artemisinin resistance and aim to eliminate all
      P. falciparum parasites. These efforts are crucial since a resurgence of malaria
      due to drug and/or insecticide resistance, program cuts, lack of political
      support and donor fatigue could set back malaria control success in the sub
      region and threaten malaria control and elimination if resistance spreads to
      other regions. 

PMID- 24033693
TI  - Epitheliocystis in three wild fish species in Tasmanian waters.

PMID- 24033692
TI  - UGT1A1*6, 1A7*3, and 1A9*22 genotypes predict severe neutropenia in FOLFIRI
      treated metastatic colorectal cancer in two prospective studies in Japan.
AB  - Retrospective studies have suggested that UDP-glucuronosyltransferase (UGT)1A1,
      UGT1A7, and UGT1A9 predict severe toxicity and efficacy of irinotecan-containing
      regimens. We prospectively evaluated the impact of UGT1A genotypes and haplotypes
      on severe toxicity and efficacy in patients treated with fluorouracil,
      leucovorin, and irinotecan combination chemotherapy (FOLFIRI) for metastatic
      colorectal cancer (mCRC) from the two prospective multicenter phase II studies in
      Japan. The FLIGHT1 study was a first-line FOLFIRI trial, and FLIGHT2 was a FOLFOX
      refractory, second-line FOLFIRI trial. A total of 73 patients agreed to
      additional analysis, and were genotyped for UGT1A polymorphisms, UGT1A1*28
      (TA6>TA7), UGT1A1*6 (211G>A), UGT1A1*27 (686C>A), UGT1A1*60 (-3279T>G), UGT1A1*93
      (-3156G>A), UGT1A7 (-57T>G), UGT1A7*3 (387T>G, 622T>C), and UGT1A9*22 (T9>T10).
      Of 73 patients, 34 developed G3/4 severe hematological toxicities. The toxicities
      were significantly more frequent in patients with UGT1A1*6 (211A), UGT1A7 (387G),
      and UGT1A9*22 reference alleles (T9). Haplotype I, which consists of all
      favorable alleles, was associated with a significant reduction in hematologic
      toxicity (P = 0.031). In contrast, haplotype II, which contains four high-risk
      alleles, showed significantly higher hematologic toxicity than the other
      haplotypes (P = 0.010). Six out of seven patients who were homozygous for
      UGT1A1*28 or *6 experienced severe hematological toxicity despite the fact that
      their response rate was not impaired (42.9%). We concluded that UGT1A
      polymorphisms, especially UGT1A1*6, are important for the prediction of severe
      toxicity of FOLFIRI in northeast Asian populations. In this regard, haplotype
      analyses should substantially impact the prediction of severe hematological
      toxicities of FOLFIRI. ( CLINICAL TRIAL REGISTRATION: UMIN000002388 and
      UMIN000002476).

PMID- 24033694
TI  - Tricuspid atresia associated with truncus arteriosus versus aortopulmonary
      window: combining fetal and postnatal echocardiography to make the diagnosis.
AB  - The coincident occurrence of tricuspid atresia and aortopulmonary window (APW) is
      exceedingly rare, with one previous case reported in the literature. We present a
      patient with tricuspid atresia, pulmonary atresia, and APW. Postnatal
      echocardiograms demonstrated no visible pulmonary valve, and additional defects
      including a bicuspid aortic valve, right aortic arch and anomalous coronary
      arteries raised suspicion for tricuspid atresia with persistent truncus
      arteriosus. However, fetal echocardiography and direct visualization of the
      anatomy confirmed the alternate diagnosis. The patient underwent successful
      palliation consisting of APW repair, atrial septectomy and a 3.5 mm modified
      Blalock-Taussig shunt, followed by a bidirectional cavopulmonary connection. 

PMID- 24033695
TI  - Editorial comment to "Recent status of the treatment of stress urinary
      incontinence".

PMID- 24033697
TI  - Diagnostic utility of D-dimer concentrations in dogs with pulmonary embolism.
AB  - BACKGROUND: Pulmonary embolism (PE) is a complication of systemic disease in
      dogs. Antemortem diagnosis is challenging because of the lack of a confirmatory
      test. OBJECTIVES: To retrospectively determine the diagnostic utility of D-dimer
      concentrations in dogs with necropsy-confirmed PE. ANIMALS: Ten dogs with PE
      confirmed at necropsy that had D-dimer concentrations measured and 10 control
      dogs with D-dimer concentrations available that lacked PE on necropsy. METHODS:
      The computerized medical record database was searched for dogs with necropsy
      confirmed PE that had D-dimer concentrations measured at that visit. An age-, sex
      , and breed-matched control group was identified. Signalment, location of PE, and
      coagulation profiles were collected. Sensitivity, specificity, negative
      predictive value (NPV), and positive predictive value (PPV) were calculated using
      a D-dimer concentration of 250 ng/mL. RESULTS: Coagulation profiles were not
      different between dogs with and without PE. Using 250 ng/mL as a cut-off D-dimer
      concentration, the sensitivity and specificity were 80 and 30%, respectively, for
      the diagnosis of PE. The NPV and PPV were 60 and 53.0%, respectively. D-dimer
      concentration <103 ng/mL had 100% sensitivity for ruling out PE and no value was
      100% specific. CONCLUSIONS AND CLINICAL IMPORTANCE: D-dimer concentrations <250
      ng/mL have a high sensitivity for the absence of PE, but PE still can occur in
      dogs with a normal D-dimer concentration. Increased D-dimer concentrations are
      not specific for PE.

PMID- 24033696
TI  - Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene
      (CYP2A6).
AB  - BACKGROUND AND AIMS: Evidence suggests that both the nicotinic receptor alpha5
      subunit (CHRNA5) and Cytochrome P450 2A6 (CYP2A6) genotypes influence smoking
      cessation success and response to pharmacotherapy. We examine the effect of
      CYP2A6 genotype on smoking cessation success and response to cessation
      pharmacotherapy, and combine these effects with those of CHRNA5 genotypes.
      DESIGN: Placebo-controlled randomized smoking cessation trial. SETTING:
      Ambulatory care facility in Wisconsin, USA. PARTICIPANTS: Smokers (n = 709) of
      European ancestry were randomized to placebo, bupropion, nicotine replacement
      therapy or combined bupropion and nicotine replacement therapy. MEASUREMENTS:
      Survival analysis was used to model time to relapse using nicotine metabolism
      derived from CYP2A6 genotype-based estimates. Slow metabolism is defined as the
      lowest quartile of estimated metabolic function. FINDINGS: CYP2A6-defined
      nicotine metabolic function moderated the effect of smoking cessation
      pharmacotherapy on smoking relapse over 90 days [hazard ratio (HR) = 2.81, 95%
      confidence interval (CI) = 1.32-5.99, P = 0.0075], with pharmacotherapy
      significantly slowing relapse in fast (HR = 0.39, 95% CI = 0.28-0.55, P = 1.97 *
      10(-8)), but not slow metabolizers (HR = 1.09, 95% CI = 0.55-2.17, P = 0.80).
      Further, only the effect of nicotine replacement, and not bupropion, varies with
      CYP2A6-defined metabolic function. The effect of nicotine replacement on
      continuous abstinence is moderated by the combined genetic risks from CYP2A6 and
      CHRNA5 (Wald = 7.44, d.f. = 1, P = 0.0064). CONCLUSIONS: Nicotine replacement
      therapy is effective among individuals with fast, but not slow, CYP2A6-defined
      nicotine metabolism. The effect of bupropion on relapse likelihood is unlikely to
      be affected by nicotine metabolism as estimated from CYP2A6 genotype. The
      variation in treatment responses among smokers with genes may guide future
      personalized smoking cessation interventions.

PMID- 24033698
TI  - Relationship between cerebral atherosclerosis and leukoaraiosis in aged patients:
      results from DSA.
AB  - BACKGROUND AND PURPOSE: There are some controversial results on the relationship
      between cerebral atherosclerosis and leukoaraiosis in the published papers, where
      cerebral atherosclerosis was often evaluated by ultrasonography, CTA or MRA. We
      analyzed data in which patients underwent both MRI and DSA to explore the above
      relationship in the aged people. METHODS: Three hundred and thirty-three patients
      were enrolled in the study from the Nanjing Stroke Registry. They underwent both
      cerebral DSA and MRI. Age, sex, and vascular risk factors were collected.
      Atherosclerosis was scored from grade 0 to 4. Leukoaraiosis was scored from grade
      0 to 3. RESULTS: Cerebral artery stenosis was not correlated with the presence of
      leukoaraiosis. There were no correlations between the number of cerebral
      moderately or more severely stenotic arteries and the severity of leukoaraiosis
      in periventricular, deep, or whole white matter (P = .747, .268, and .608,
      respectively). Old age (odds ratio = 1.103, P = .027) and hypertension (odds
      ratio = 2.748, P = .003) were correlated with leukoaraiosis in the
      periventricular white matter. Old age (odds ratio = 1.073, P = .031) and prior
      stroke (odds ratio = 2.678, P = .002) were correlated with leukoaraiosis in the
      deep white matter. CONCLUSIONS: No apparent correlation exists between cerebral
      artery stenosis and the presence and severity of leukoaraiosis.

PMID- 24033699
TI  - Endothelial function and sleep: associations of flow-mediated dilation with
      perceived sleep quality and rapid eye movement (REM) sleep.
AB  - Endothelial function typically precedes clinical manifestations of cardiovascular
      disease and provides a potential mechanism for the associations observed between
      cardiovascular disease and sleep quality. This study examined how subjective and
      objective indicators of sleep quality relate to endothelial function, as measured
      by brachial artery flow-mediated dilation (FMD). In a clinical research centre,
      100 non-shift working adults (mean age: 36 years) completed FMD testing and the
      Pittsburgh Sleep Quality Index, along with a polysomnography assessment to obtain
      the following measures: slow wave sleep, percentage rapid eye movement (REM)
      sleep, REM sleep latency, total arousal index, total sleep time, wake after sleep
      onset, sleep efficiency and apnea-hypopnea index. Bivariate correlations and
      follow-up multiple regressions examined how FMD related to subjective (i.e.,
      Pittsburgh Sleep Quality Index scores) and objective (i.e., polysomnography
      derived) indicators of sleep quality. After FMD showed bivariate correlations
      with Pittsburgh Sleep Quality Index scores, percentage REM sleep and REM latency,
      further examination with separate regression models indicated that these
      associations remained significant after adjustments for sex, age, race,
      hypertension, body mass index, apnea-hypopnea index, smoking and income (Ps <
      0.05). Specifically, as FMD decreased, scores on the Pittsburgh Sleep Quality
      Index increased (indicating decreased subjective sleep quality) and percentage
      REM sleep decreased, while REM sleep latency increased (Ps < 0.05). Poorer
      subjective sleep quality and adverse changes in REM sleep were associated with
      diminished vasodilation, which could link sleep disturbances to cardiovascular
      disease.

PMID- 24033700
TI  - The effects of the 2006 Russian alcohol policy on alcohol-related mortality: an
      interrupted time series analysis.
AB  - BACKGROUND: The aim of this study was to determine the impact of a set of 2006
      Russian alcohol policies on alcohol-related mortality in the country. METHODS: We
      used autoregressive integrated moving average interrupted time series techniques
      to model the impact of the policy on the number of sex-specific monthly deaths of
      those aged 15+ years due to alcohol poisoning, alcoholic cardiomyopathy,
      alcoholic liver cirrhosis, and alcohol-related mental and behavioral disorders.
      The time series began in January 2000 and ended in December 2010. The alcohol
      policy was implemented in January 2006. RESULTS: The alcohol policy resulted in a
      significant gradual and sustained decline in male deaths due to alcohol poisoning
      (omegao = -92.631, p < 0.008, delta1 = 0.883, p < 0.001) and in significant
      immediate and sustained declines in male (omega0 = -63.20, p < 0.05) and female
      (omega0 = -64.28, p < 0.005) deaths due to alcoholic liver cirrhosis.
      CONCLUSIONS: The 2006 suite of alcohol policies in Russia was responsible for an
      annual decline of about 6,700 male alcohol poisoning deaths and about 760 male
      and about 770 female alcoholic liver cirrhosis deaths. Without the alcohol
      policy, male alcohol poisoning deaths would have been 35% higher and male and
      female alcoholic liver cirrhosis deaths would have been 9 and 15% higher,
      respectively. We contextualize our findings in relation to declining mortality in
      Russia and to results from recent studies of the impact of this law on other
      causes of death.

PMID- 24033701
TI  - Providing habitat for native mammals through understory enhancement in forestry
      plantations.
AB  - The Convention on Biological Diversity (CBD) expects forestry plantations to
      contribute to biodiversity conservation. A well-developed understory in forestry
      plantations might serve as a surrogate habitat for native species and mitigate
      the negative effect of plantations on species richness. We experimentally tested
      this hypothesis by removing the understory in Monterey pine (Pinus radiata)
      plantations in central Chile and assessing changes in species richness and
      abundance of medium-sized mammals. Frequency of occurrence of mammals, including
      kodkods (Leopardus guigna), culpeo foxes (Pseudalopex culpaeus), lesser grisons
      (Conepatus chinga), and Southern pudu deer (Pudu puda), was low in forest stands
      with little to no understory relative to stands with well-developed undergrowth
      vegetation. After removing the understory, their frequency of occurrence
      decreased significantly, whereas in control stands, where understory was not
      removed, their frequency did not change. This result strongly supports the idea
      that facilitating the development of undergrowth vegetation may turn forestry
      stands into secondary habitats as opposed to their containing no habitat for
      native mammals. This forestry practice could contribute to conservation of
      biological diversity as it pertains to CBD targets.

PMID- 24033702
TI  - The effects of varenicline on alcohol seeking and self-administration in baboons.
AB  - BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) may play a critical role
      in alcohol reinforcement and consumption. The effects of varenicline, an nAChR
      partial agonist, on alcohol seeking and self-administration responses were
      evaluated in 2 groups of baboons trained under a 3-component chained schedule of
      reinforcement (CSR). METHODS: Alcohol (4% w/v; n = 4; alcohol group) or a
      preferred nonalcoholic beverage (n = 4; control group) was available for self
      administration only in component 3 of the CSR. Responses in component 2, required
      to gain access to alcohol, provided indices of seeking behavior. Varenicline
      (0.032 to 0.32 mg/kg; 0.32 mg/kg twice daily [BID]) and vehicle were administered
      before CSR sessions subchronically (5 consecutive days). Higher doses (0.56, 1.0
      mg/kg) were attempted, but discontinued due to adverse effects. RESULTS:
      Subchronic varenicline administration significantly (p < 0.05) decreased the
      seeking response rate and increased the time to complete the response requirement
      to gain access to the daily supply of alcohol at the higher doses (0.32 mg/kg,
      0.32 mg/kg BID dosing) in the alcohol group compared with the control group. Mean
      number of drinks was significantly decreased (p < 0.05), but effects did not
      differ between groups. The pattern of drinking was characterized by a high rate
      during an initial bout. Number of drinks during and duration of the initial bout
      were significantly decreased in the alcohol group, compared with the control
      group, at 0.32 mg/kg (p < 0.05). CONCLUSIONS: Varenicline may be clinically
      useful for reducing alcohol-seeking behaviors prior to alcohol exposure. Given
      the modest effects on drinking itself, varenicline may be better suited as a
      treatment in combination with a pharmacotherapy that significantly reduces
      alcohol consumption.

PMID- 24033703
TI  - Recent pregnancy trends among early adolescent girls in Japan.
AB  - AIM: The paper examines recent time trends, explores potentially influential
      background factors and discusses prevention strategies of pregnancy among girls
      under 15 years of age in Japan. METHODS: Using Japanese government data, we first
      analyzed time trends of early adolescence (<15 years of age) abortion, live birth
      and child sexual abuse from 2003 to 2010. Second, we analyzed ecological
      correlations of early adolescent pregnancy (abortion, live birth and stillbirth)
      with pregnancy in other age groups, child sexual abuse, and indicators of
      juvenile victimization and juvenile delinquency, using prefectural data. RESULTS:
      We found that rates of both abortion and live birth in early adolescents have
      increased since 2005 (annual percent change 5.3% and 2.3%, respectively), despite
      declining rates in older age groups. The abortion ratio in early adolescence
      remained the highest among all age groups in Japan. The early adolescent
      pregnancy rate showed significant correlation with the rates of juvenile
      victimization of welfare crimes (obscenity, alcohol drinking, smoking and drug
      use) (Spearman's rank correlation coefficient [rs] = 0.42, P = 0.00) and juvenile
      delinquency among junior high school students (12-14 years of age) (rs = 0.69, P
      = 0.00). CONCLUSION: The observed rise in rates of abortion, live birth and child
      sexual abuse among early adolescents along with strong ecological correlations of
      their pregnancy rate with juvenile victimization and delinquency indicators
      suggests that epidemiological investigation and public health programs at the
      individual and community levels are needed to address the complex social roots of
      these trends and to produce effective improvements in early adolescent
      reproductive health.

PMID- 24033704
TI  - The Zyxin-related protein thyroid receptor interacting protein 6 (TRIP6) is
      overexpressed in Ewing's sarcoma and promotes migration, invasion and cell
      growth.
AB  - BACKGROUND INFORMATION: Ewing's sarcoma (ES) is the second most common bone
      associated malignancy in children and is driven by the fusion oncogene EWS/FLI1
      and characterised by rapid growth and early metastasis. Here, we explored the
      role of the Zyxin-related protein thyroid receptor interacting protein 6 (TRIP6)
      in ES. The Zyxin family comprises seven homologous proteins involved in migration
      and proliferation of many cell types of which Zyxin has been described as a
      tumour suppressor in ES. RESULTS: By interrogation of published microarray data
      (n = 1254), we observed that of all Zyxin proteins, only TRIP6 is highly
      overexpressed in primary ES compared with normal tissues. Re-analysis of
      published EWS/FLI1 gain- and loss-of-function microarray experiments as well as
      chromatin-immunoprecipitation assays revealed that TRIP6 overexpression is not
      mediated by EWS/FLI1. Microarray and subsequent gene-set enrichment analyses of
      ES cells with and without RNA interference-mediated TRIP6 knockdown demonstrated
      that TRIP6 expression confers a pro-proliferative and pro-invasive
      transcriptional signature to ES cells. While short-term proliferation was not
      considerably affected by TRIP6 knockdown, silencing of the protein significantly
      reduced migration, invasion, long-term proliferation and clonogenicity of ES
      cells in vitro as well as tumourigenicity in vivo. CONCLUSIONS: Taken together,
      our data indicate that TRIP6 acts, in contrast to Zyxin, as an oncogene that
      partially accounts for the autonomous migratory, invasive and proliferative
      properties of ES cells independent of EWS/FLI1.

PMID- 24033705
TI  - Interhospital transfers from U.S. emergency departments: implications for
      resource utilization, patient safety, and regionalization.
AB  - OBJECTIVES: The authors sought to describe the demographic and clinical
      characteristics of interhospital transfers from U.S. emergency departments (EDs)
      along with the primary reasons for transfers. METHODS: This was a retrospective,
      cross-sectional analysis of the 1997 through 2009 National Hospital Ambulatory
      Medical Care Survey (NHAMCS). Visit-level characteristics were compared for
      patients who were transferred, admitted, or discharged. Additionally, data on
      primary reason for transfer for available years (2005 through 2008) were
      reviewed. Weighted analyses produced nationally representative estimates.
      RESULTS: During this time period, 1.8% (95% confidence interval [CI] = 1.7% to
      2.0%) of ED patients were transferred to other hospitals. Compared to visits
      resulting in admission, those resulting in transfer were more likely to involve
      patients who were <18 years old (18% vs. 7.9%), male (53% vs. 46%), with Medicaid
      (22% vs. 16%) or self-payment (15% vs. 8.2%) as a primary expected source of
      payment, having a visit related to injury (40% vs. 19%), and from a nonurban ED
      (29% vs. 15%). Among transferred patients, 28% (95% CI = 27% to 30%) received
      four to six diagnostic tests, and 31% (95% CI = 29% to 34%) received more than
      six diagnostic tests prior to transfer; 52% (95% CI = 50% to 54%) had diagnostic
      imaging, and 17% (95% CI = 16% to 19%) had cross-sectional imaging. Of the
      patients transferred from 2005 through 2008, 47% (95% CI = 43% to 53%) were
      transferred for a higher level of care, and 29% (95% CI = 26% to 35%) were
      transferred for psychiatric care. CONCLUSIONS: Transfer of ED patients was
      relatively rare, but was more common among specific, potentially high-risk
      populations. Diagnostic testing, including advanced imaging, was common prior to
      transfer. A majority of transfers were for reasons indicating limited resources
      or expertise at the referring facility.

PMID- 24033706
TI  - Visual cortex organisation in a macaque monkey with macular degeneration.
AB  - The visual field is retinotopically represented in early visual areas. It has
      been suggested that when adult primary visual cortex (V1) is deprived of normal
      retinal input it is capable of large-scale reorganisation, with neurons inside
      the lesion projection zone (LPZ) being visually driven by inputs from intact
      retinal regions. Early functional magnetic resonance imaging (fMRI) studies in
      humans with macular degeneration (MD) report > 1 cm spread of activity inside the
      LPZ border, whereas recent results report no shift of the LPZ border. Here, we
      used fMRI population receptive field measurements to study, for the first time,
      the visual cortex organisation of one macaque monkey with MD and to compare it
      with normal controls. Our results showed that the border of the V1 LPZ remained
      stable, suggesting that the deafferented area V1 zone of the MD animal has
      limited capacity for reorganisation. Interestingly, the pRF size of non
      deafferented V1 voxels increased slightly (~20% on average), although this effect
      appears weaker than that in previous single-unit recording reports. Area V2 also
      showed limited reorganisation. Remarkably, area V5/MT of the MD animal showed
      extensive activation compared to controls stimulated over the part of the visual
      field that was spared in the MD animal. Furthermore, population receptive field
      size distributions differed markedly in area V5/MT of the MD animal. Taken
      together, these results suggest that V5/MT has a higher potential for
      reorganisation after MD than earlier visual cortex. 

PMID- 24033707
TI  - The adverse events profile of anti-IGF-1R monoclonal antibodies in cancer
      therapy.
AB  - AIM(S): Insulin-like growth factor-1 receptor (IGF-1R) targeted therapies have
      become one of the intriguing areas in anticancer drug development during the last
      decade. As one of these therapies, anti-IGF-1R monoclonal antibodies (mAbs) are
      also advancing further in development. Our purpose was to conduct a systematic
      review of the adverse events (AEs) caused by anti-IGF-1R monoclonal antibodies in
      cancer therapy. METHODS: We searched the term'IGF-1R monoclonal antibody' in the
      Pubmed database and found 389 related articles. After elaborate selection, 15
      clinical studies that satisfied our criteria were then adopted for further
      analysis. We extracted all the useful information about the AEs of mAbs from the
      enrolled studies. Every kind of reported AE as well as corresponding incidences
      were summed up and calculated. We compared AE incidence differences in two age
      groups, and analyzed toxicities of mAbs used as a single agent or combined with
      chemotherapies. Finally, the differences of AE profiles between individual mAbs
      were also valued. RESULTS: AEs were more severe in the lower age group and 13 of
      19 AE incidences in the single-agent group were significantly lower than in the
      combination group (P < 0.05). R1507 seemed to show a worse AE profile than
      cixutumumab and figitumumab. CONCLUSIONS: When anti-IGF-1R mAbs are used for
      cancer therapy, it is essential to choose the proper drug and combined
      chemotherapies to reduce AE occurrences. Also, administration of these mAbs to
      younger patients should be more carefully supervised. Furthermore, some more
      frequently observed AEs for specific mAb should be paid adequate attention.

PMID- 24033708
TI  - Cognitive enhancement in children and adolescents: is it in their best interests?
AB  - Evidence suggests children and adolescents are consuming stimulants and
      nonstimulants in the hopes of improving academic performance through cognitive
      enhancement. As such, clinicians may be faced with requests to prescribe
      enhancers for their paediatric patients. In this article, we analyse the ethics
      of cognitive enhancement in paediatrics in the light of the best interests
      standard, a guiding principle, often used to make decisions for minors in moral,
      legal, social and medical contexts. CONCLUSION: Cognitive enhancement in children
      and adolescents does not represent an ethical ideal that societies should strive
      for. Furthermore, paediatric cognitive enhancement does not meet the criteria for
      a minimally acceptable practice, given the health-related risks posed by these
      medications and the coercive environments such a practice creates. In line with a
      recent policy statement by the American Academy of Neurology, ethical and
      clinical arguments based on the best interests of paediatric patients encourage
      clinicians to refrain from engaging in this practice.

PMID- 24033710
TI  - Congenital thrombotic thrombocytopenic purpura caused by new compound
      heterozygous mutations of the ADAMTS13 gene.
AB  - Upshaw-Schulman syndrome (USS) is due to severe congenital deficiency of von
      Willebrand factor (VWF)-cleaving protease ADAMTS13 (a disintegrin and
      metalloprotease with thrombospondin type 1 domains, nr 13) activity resulting in
      the presence of unusually large forms of VWF in the circulation, causing
      intravascular platelet clumping and thrombotic microangiopathy. Our patient, a 26
      year-old man, had attacks of thrombotic thrombocytopenic purpura (TTP) with
      thrombocytopenia and a urine dipstick positive for hemoglobin (4+), often as the
      only sign of hemolytic activity. He had ADAMTS13 activity of <1% of normal plasma
      without the presence of inhibitors of ADAMTS13. ADAMTS13 deficiency was caused by
      two new mutations of the ADAMTS13 gene: a deletion of a single nucleotide in
      exon17 (c. 2042 delA) leading to a frameshift (K681C fs X16), and a missense
      mutation in exon 25 (c.3368G>A) leading to p.R1123H. This case report confirms
      the importance of the analysis of the ADAMTS13 activity and its inhibitor in
      patients who have episodes of TTP, with a very low platelet count and sometimes
      without the classic biochemical signs of hemolysis. 

PMID- 24033709
TI  - Lack of functional TSLP receptors mitigates Th2 polarization and the
      establishment and growth of 4T1 primary breast tumours but has different effects
      on tumour quantities in the lung and brain.
AB  - The 4T1 mammary carcinoma cell line produces TSLP. We had hypothesized that TSLP
      promotes the development of a permissive environment for the growth and
      metastasis of primary tumour and that this is associated with a Th2-polarized
      antitumour immune response. We found that, in Tslpr(-/-) mice, the mean tumour
      diameters were smaller from days 27 to 40, and relatively fewer tumour cells were
      present in the lung, compared with wild-type mice. Polarization of the Th2
      cytokine profile was also diminished in Tslpr(-/-) mice. These findings confirmed
      those reported previously by others. Here, we further show that primary tumours
      are established less often in Tslpr(-/-) mice and that, unexpectedly, the
      relative number of tumour cells in the brain is greater in Tslpr(-/-) mice
      compared with wild-type mice. Findings from our cytotoxicity assays show that 4T1
      directed lysis is undetectable in both WT and Tslpr(-/-) mice, ruling out the
      possibility that altered cytotoxic responses in Tslpr(-/-) mice are responsible
      for the differences we observed. In a human tissue microarray, positive staining
      for TSLP was seen in tumour cells from breast cancer tissue, but it was also seen
      in normal glandular epithelial cells from normal breast tissue, which has not
      been shown before. Thus, our findings provide new insight into the effects of
      TSLP in metastatic breast cancer. 

PMID- 24033711
TI  - Streptococcus bovis group and biliary tract infections: an analysis of 51 cases.
AB  - Streptococcus bovis is a well-known cause of endocarditis, but its role in other
      infections has not been well described. We analysed prospectively all patients
      with biliary tract infections caused by S. bovis group during the period 1988
      2011. We selected those cases associated with cholangitis and cholecystitis,
      defined according to Tokyo guidelines. Identification of the strains was
      performed using the API 20 Strep and the GP card of the Vitek 2 system, and was
      confirmed by molecular methods. Our series included 51 cases (30 cholangitis and
      21 cholecystitis). The associated microorganisms were: Streptococcus infantarius
      (biotype II/1) 29 cases (57%), Streptococcus gallolyticus subsp. pasteurianus
      (biotype II/2) 20 cases (39%) and Streptococcus gallolyticus subsp. gallolyticus
      (biotype I) two cases (4%). The only difference found between S. infantarius and
      S. gallolyticus subsp. pasteurianus was a greater association of the first with
      malignant strictures of the bile ducts: 48% (14/29) versus 5% (1/20), p <0.001.
      Thirty-seven of the cases also had bacteraemia, causing 20% (37/185) of all S.
      bovis bacteraemia, with differences between S. gallolyticus subsp. gallolyticus
      (2/112; 2%) and the other two microorganisms: S. infantarius and S. gallolyticus
      subsp. pasteurianus (35/73; 48%; p <0.001). The vast majority of biliary tract
      infections due to S. bovis group are caused by S. infantarius and S. gallolyticus
      subsp. pasteurianus (S. bovis biotype II), and nearly half of the bacteraemia due
      to these two species has a biliary source (43% of the S. infantarius and 56% of
      S. gallolyticus subsp. pasteurianus).

PMID- 24033712
TI  - Editorial: Looking to the future with courage, commitment, competence and
      compassion.

PMID- 24033713
TI  - Validation of the Swedish version of the Nursing Delirium Screening Scale used in
      patients 70 years and older undergoing cardiac surgery.
AB  - AIMS AND OBJECTIVES: Validation of the Swedish version of the Nursing Delirium
      Screening Scale as a screening tool for nurses to use to detect postoperative
      delirium in patients 70 years and older undergoing cardiac surgery. BACKGROUND:
      Delirium is common among old patients after cardiac surgery. Underdiagnosis and
      poor documentation of postoperative delirium is problematic, and nurses often
      misread the signs. DESIGN: A prospective observational study. METHODS: Patients
      (n = 142) scheduled for cardiac surgery were assessed three times daily by the
      nursing staff using the Nursing Delirium Screening Scale. Nursing Delirium
      Screening Scale was compared with the Mini Mental State Examination and the
      Organic Brains Syndrome Scale, evaluated day one and day four postoperatively.
      Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental
      Disorders - DSM-IV-TR criteria. RESULTS: A larger proportion of patients were
      diagnosed with delirium according to the Mini Mental State Examination and
      Organic Brains Syndrome Scale compared with the Nursing Delirium Screening Scale,
      both on day one and day four. The Nursing Delirium Screening Scale protocol
      identified the majority of hyperactive and mixed delirium patients, whereas
      several with hypoactive delirium were unrecognised. CONCLUSIONS: The Swedish
      version of the Nursing Delirium Screening Scale was easily incorporated into
      clinical care and showed high sensitivity in detecting hyperactive symptoms of
      delirium. However, in the routine use by nurses, the Nursing Delirium Screening
      Scale had low sensitivity in detecting hypoactive delirium, the most prevalent
      form of delirium after cardiac surgery. Nursing Delirium Screening Scale probably
      has to be combined with cognitive testing to detect hypoactive delirium.
      RELEVANCE TO CLINICAL PRACTICE: Nurses play a key role in detecting delirium. The
      Nursing Delirium Screening Scale was easy incorporated instrument for clinical
      practice and identified the majority of hyperactive and mixed delirium, but
      several of the patients with hypoactive delirium were unrecognised. Training of
      assessment and cognitive testing seems to be necessary to detect hypoactive
      delirium.

PMID- 24033715
TI  - Altered cingulate and insular cortex activation during risk-taking in
      methamphetamine dependence: losses lose impact.
AB  - AIMS: To determine if methamphetamine-dependent (MD) individuals exhibit
      behavioral or neural processing differences in risk-taking relative to healthy
      comparison participants (CTL). DESIGN: This was a cross-sectional study comparing
      two groups' behavior on a risk-taking task and neural processing as assessed
      using functional magnetic resonance imaging (fMRI). SETTINGS: The study was
      conducted in an in-patient treatment center and a research fMRI facility in the
      United States. PARTICIPANTS: Sixty-eight recently abstinent MD individuals
      recruited from a treatment program and 40 CTL recruited from the community
      completed the study. MEASUREMENTS: The study assessed risk-taking behavior
      (overall and post-loss) using the Risky Gains Task (RGT), sensation-seeking,
      impulsivity and blood-oxygenation-level-dependent activation in the brain during
      the decision phase of the RGT. FINDINGS: Relative to CTL, MD displayed decreased
      activation in the bilateral rostral anterior cingulate cortex (ACC) and greater
      activation in the left insula across risky and safe decisions (P < 0.05). Right
      mid-insula activation among CTL did not vary between risky and safe decisions,
      but among MD it was higher during risky relative to safe decisions (P < 0.05).
      Among MD, lower activation in the right rostral ACC (r = -0.39, P < 0.01) and
      higher activation in the right mid-insula (r = 0.35, P < 0.01) during risky
      decisions were linked to a higher likelihood of choosing a risky option following
      a loss. CONCLUSIONS: Methamphetamine-dependent individuals show disrupted risk
      related processing in both anterior cingulate and insula, brain areas that have
      been implicated in cognitive control and interoceptive processing. Attenuated
      neural processing of risky options may lead to risk-taking despite experiencing
      negative consequences.

PMID- 24033716
TI  - Recovery of Pseudomonas koreensis from eye lesions in golden mahseer, Tor
      putitora (Hamilton, 1822) in Uttarakhand, India.

PMID- 24033717
TI  - Modeling uncertainties in workforce disruptions from influenza pandemics using
      dynamic input-output analysis.
AB  - Influenza pandemic is a serious disaster that can pose significant disruptions to
      the workforce and associated economic sectors. This article examines the impact
      of influenza pandemic on workforce availability within an interdependent set of
      economic sectors. We introduce a simulation model based on the dynamic input
      output model to capture the propagation of pandemic consequences through the
      National Capital Region (NCR). The analysis conducted in this article is based on
      the 2009 H1N1 pandemic data. Two metrics were used to assess the impacts of the
      influenza pandemic on the economic sectors: (i) inoperability, which measures the
      percentage gap between the as-planned output and the actual output of a sector,
      and (ii) economic loss, which quantifies the associated monetary value of the
      degraded output. The inoperability and economic loss metrics generate two
      different rankings of the critical economic sectors. Results show that most of
      the critical sectors in terms of inoperability are sectors that are related to
      hospitals and health-care providers. On the other hand, most of the sectors that
      are critically ranked in terms of economic loss are sectors with significant
      total production outputs in the NCR such as federal government agencies.
      Therefore, policy recommendations relating to potential mitigation and recovery
      strategies should take into account the balance between the inoperability and
      economic loss metrics. 

PMID- 24033718
TI  - Increased mortality rate and suicide in Swedish former elite male athletes in
      power sports.
AB  - Physical training has been shown to reduce mortality in normal subjects, and
      athletes have a healthier lifestyle after their active career as compared with
      normal subjects. Since the 1950s, the use of anabolic androgenic steroids (AAS)
      has been frequent, especially in power sports. The aim of the present study was
      to investigate mortality, including causes of death, in former Swedish male elite
      athletes, active 1960-1979, in wrestling, powerlifting, Olympic lifting, and the
      throwing events in track and field when the suspicion of former AAS use was high.
      Results indicate that, during the age period of 20-50 years, there was an excess
      mortality of around 45%. However, when analyzing the total study period, the
      mortality was not increased. Mortality from suicide was increased 2-4 times among
      the former athletes during the period of 30-50 years of age compared with the
      general population of men. Mortality rate from malignancy was lower among the
      athletes. As the use of AAS was marked between 1960 and 1979 and was not doping
      listed until 1975, it seems probable that the effect of AAS use might play a part
      in the observed increased mortality and suicide rate. The otherwise healthy
      lifestyle among the athletes might explain the low malignancy rates. 

PMID- 24033719
TI  - Clinical and economic value of performing dialysis vascular access procedures in
      a freestanding office-based center as compared with the hospital outpatient
      department among Medicare ESRD beneficiaries.
AB  - Dialysis vascular access (DVA) care is being increasingly provided in
      freestanding office-based centers (FOC). Small-scale studies have suggested that
      DVA care in a FOC results in favorable patient outcomes and lower costs. To
      further evaluate this issue, data were drawn from incident and prevalent ESRD
      patients within a 4-year sample (2006-2009) of Medicare claims (USRDS) on cases
      who receive at least 80% of their DVA care in a FOC or a hospital outpatient
      department (HOPD). Using propensity score matching techniques, cases with a
      similar clinical and demographic profile from these two sites of service were
      matched. Medicare utilization, payments, and patient outcomes were compared
      across the matched cohorts (n = 27,613). Patients treated in the FOC had
      significantly better outcomes (p < 0.001), including fewer related or unrelated
      hospitalizations (3.8 vs. 4.4), vascular access-related infections (0.18 vs.
      0.29), and septicemia-related hospitalizations (0.15 vs. 0.18). Mortality rate
      was lower (47.9% vs. 53.5%) as were PMPM payments ($4,982 vs. $5,566). This study
      shows that DVA management provided in a FOC has multiple advantages over that
      provided in a HOPD. 

PMID- 24033720
TI  - Radiographic outcome and complications of tibial plateau leveling osteotomy
      stabilized with an anatomically contoured locking bone plate.
AB  - OBJECTIVE: To evaluate the short-term clinical performance of an anatomically pre
      contoured, locking plate in dogs undergoing tibial plateau leveling osteotomy
      (TPLO) for cranial cruciate ligament (CrCL) disease. STUDY DESIGN: Prospective,
      multi-center clinical study. ANIMALS: Dogs (n = 56) undergoing TPLO. METHODS:
      Signalment and operative data were recorded. Preoperative, postoperative, and
      follow-up tibial plateau angle (TPA) were measured from radiographic images.
      Intraoperative and postoperative complications were recorded; the latter were
      categorized as minor if additional surgery was not necessary, and major if
      surgery was needed to resolve the complication. Bone healing was scored and
      change in tibial plateau angle (TPACH ) between postoperative and follow up
      radiographic images was calculated. RESULTS: Mean (+/- SD) preoperative TPA was
      28.6 +/- 3.8 degrees , and mean postoperative TPA was 4.8 +/- 1.9 degrees . Four
      intraoperative complications (7.1%) including 2 cases of intra-articular screw
      placement, 3 minor postoperative complications (5.4%), and no major or
      catastrophic postoperative complications occurred. Median bone healing grade was
      4/4 (excellent union >75% healing). Mean TPACH was 0.15 +/- 1.32 degrees .
      CONCLUSIONS: Use of this anatomically contoured, locking TPLO plate by
      experienced surgeons is associated with accurate tibial plateau leveling,
      reliably excellent bone union at follow-up exam, minimal TPACH , and a lower
      complication rate than previously reported. Confining contouring to the distal
      shaft of the plate ensures there is precise apposition to the tibial diaphysis
      and mitigates the risk of intra-articular screw placement.

PMID- 24033721
TI  - Interaction between avoidance of photon absorption, excess energy dissipation and
      zeaxanthin synthesis against photooxidative stress in Arabidopsis.
AB  - Plants evolved photoprotective mechanisms in order to counteract the damaging
      effects of excess light in oxygenic environments. Among them, chloroplast
      avoidance and non-photochemical quenching concur in reducing the concentration of
      chlorophyll excited states in the photosynthetic apparatus to avoid
      photooxidation. We evaluated their relative importance in regulating excitation
      pressure on photosystem II. To this aim, genotypes were constructed carrying
      mutations impairing the chloroplast avoidance response (phot2) as well as
      mutations affecting the biosynthesis of the photoprotective xanthophyll
      zeaxanthin (npq1) or the activation of non-photochemical quenching (npq4),
      followed by evaluation of their photosensitivity in vivo. Suppression of
      avoidance response resulted in oxidative stress under excess light at low
      temperature, while removing either zeaxanthin or PsbS had a milder effect. The
      double mutants phot2 npq1 and phot2 npq4 showed the highest sensitivity to
      photooxidative stress, indicating that xanthophyll cycle and qE have additive
      effects over the avoidance response. The interactions between non-photochemical
      quenching and avoidance responses were studied by analyzing the kinetics of
      fluorescence decay and recovery at different light intensities. phot2
      fluorescence decay lacked a component, here named as qM. This kinetic component
      linearly correlated with the leaf transmittance changes due to chloroplast
      relocation induced by white light and was absent when red light was used as
      actinic source. On these basis we conclude that a decrease in leaf optical
      density affects the apparent non-photochemical quenching (NPQ) rise kinetic.
      Thus, excess light-induced fluorescence decrease is in part due to avoidance of
      photon absorption rather than to a genuine quenching process. 

PMID- 24033722
TI  - Lower gefitinib dose led to earlier resistance acquisition before emergence of
      T790M mutation in epidermal growth factor receptor-mutated lung cancer model.
AB  - Non-small-cell lung cancers with epidermal growth factor receptor (EGFR)
      mutations are sensitive to EGFR tyrosine kinase inhibitors (TKIs); however,
      unlike cytotoxic agents, it is generally accepted that minimal doses of drugs
      inhibiting target molecules are sufficient when molecular-targeted agents,
      including EGFR-TKIs, are used. Thus, any utility of higher doses remains unclear.
      We compared low-dose (15 mg/kg) gefitinib therapy with high-dose (50 mg/kg)
      therapy using an EGFR-mutated lung cancer xenograft model. Both gefitinib doses
      induced tumor shrinkage, but tumors regrew in the low-dose group within 1 month,
      whereas tumors in the high-dose group did not. Neither the T790M mutation nor MET
      amplification was apparent in regrown tumors. We also compared outcomes after two
      doses of gefitinib (5 and 25 mg/kg) in a transgenic EGFR-mutated lung cancer
      mouse model. In line with the results obtained using the xenograft model, both
      gefitinib doses completely inhibited tumor growth, but tumors treated with the
      lower dose of gefitinib developed earlier drug resistance. In conclusion, a low
      gefitinib dose caused tumors to become drug-resistant prior to acquisition of the
      T790M mutation or MET amplification in EGFR-mutated models of lung cancer. This
      suggests that it is important to optimize the EGFR-TKI dose for treatment of EGFR
      mutation-associated lung cancer. Gefitinib may need to be given at a dose greater
      than the minimum required for inhibition of target molecules.

PMID- 24033723
TI  - Editorial comment to Bone dissemination of prostate cancer after holmium laser
      enucleation of the prostate: a case report and a review of the literature.

PMID- 24033724
TI  - The A-dip of aortic regurgitation.
AB  - Careful analysis of the aortic regurgitation (AR) Doppler signal often provides
      important information regarding left heart hemodynamics. Here we illustrate a
      pattern on the AR signal, known as the A-dip that suggests the presence of
      elevated LVEDP. 

PMID- 24033725
TI  - One-year results of a prospective, randomized trial comparing two machine
      perfusion devices used for kidney preservation.
AB  - Studies have shown beneficial effects of machine perfusion (MP) on early kidney
      function and long-term graft survival. The aim of this study was to investigate
      whether the type of perfusion device could affect outcome of transplantation of
      deceased donor kidneys. A total of 50 kidneys retrieved from 25 donors were
      randomized to machine perfusion using a flow-driven (FD) device (RM3; Waters
      Medical Inc) or a pressure-driven (PD) device (LifePort; Organ Recovery Systems),
      24 of these kidneys (n = 12 pairs; 48%) were procured from expanded criteria
      donors (ECD). The primary endpoints were kidney function after transplantation
      defined using the incidence of delayed graft function (DGF), the number of
      hemodialysis sessions required, graft function at 12 months, and analyses of
      biopsy. DGF was similar in both groups (32%; 8/25). Patients with DGF in the FD
      group required a mean of 4.66 hemodialysis sessions versus 2.65 in the PD group
      (P = 0.005). Overall, 1-year graft survival was 80% (20/25) vs. 96% (24/25) in
      the FD and PD groups. One-year graft survival of ECD kidneys was 66% (8/12) in
      the FD group versus 92% (11/12) in the PD group. Interstitial fibrosis and
      tubular atrophy were significantly more common in the FD group - 45% (5/11) vs.
      0% (0/9) (P = 0.03) in PD group. There were no differences in creatinine levels
      between the groups. Machine perfusion using a pressure-driven device generating
      lower pulse stress is superior to a flow-driven device with higher pulse stress
      for preserving kidney function.

PMID- 24033726
TI  - A novel biomaterial: bacterial cellulose and its new era applications.
AB  - Bacterial cellulose (BC) is a promising natural polymer that is produced by
      bacteria and that has unique and desirable structural, physical, and chemical
      properties. From the time when the remarkable properties of BC were found 15
      years ago compared with plant cellulose, interest has grown in BC and it has
      become an article of trade in diverse applications. Following this trend, this
      paper reviews the progress of relevant studies, including general information
      about cellulose, production by microorganisms as well as BC cultivation, and its
      properties. The applications reviewed in the present article comprise biological
      and nonbiological fields. The latest use of BC in the biomedical, environmental,
      agricultural, electronic, food, and industrial fields is discussed with its
      applications in composite form. The present article attempts to amass the
      assorted uses of BC under one umbrella. Thus, recent advances in BC applications
      in different fields are thoroughly reviewed. This article concludes with the need
      for future research of BC to make it commercialized as vital biomaterial. 

PMID- 24033727
TI  - Hypersomnia with dilated pupils in adenosine monophosphate deaminase (AMPD)
      deficiency.

PMID- 24033728
TI  - Prediction of tamoxifen outcome by genetic variation of CYP2D6 in post-menopausal
      women with early breast cancer.
AB  - The question of whether genetic polymorphisms of CYP2D6 can affect treatment
      outcome in patients with early post-menopausal oestrogen receptor (ER)-positive
      breast cancer has been a matter of debate over the past few years. In this
      article we revisit the hypothesis of CYP2D6 being a potential tamoxifen outcome
      predictor and provide detailed insight into the ongoing controversy that
      prevented the CYP2D6 marker from being accepted by the scientific and clinical
      community. We summarize the available pharmacokinetic, pharmacodynamic and
      pharmacogenetic evidence and resolve the controversy based on the recognized
      methodological and statistical issues. The cumulative evidence suggests that
      genotyping for CYP2D6 is clinically relevant in post-menopausal women. This is
      important, because the clarification of this issue has the potential to resolve a
      clinical management question that is relevant to hundreds of thousands of women
      diagnosed with ER-positive breast cancer each year, who should not be denied
      effective endocrine therapy. 

PMID- 24033729
TI  - Activation of the epithelial-to-mesenchymal transition factor snail mediates
      acetaldehyde-induced intestinal epithelial barrier disruption.
AB  - BACKGROUND: Acetaldehyde (AcH) is mutagenic and can reach high concentrations in
      colonic lumen after ethanol consumption and is associated with intestinal barrier
      dysfunction and an increased risk of progressive cancers, including colorectal
      carcinoma. Snail, the transcription factor of epithelial-mesenchymal transition,
      is known to down-regulate expression of tight junction (TJ) and adherens junction
      (AJ) proteins, resulting in loss of epithelial integrity, cancer progression, and
      metastases. As AcH is mutagenic, the role of Snail in the AcH-induced disruption
      of intestinal epithelial TJs deserves further investigation. Our aim was to
      investigate the role of oxidative stress and Snail activation in AcH-induced
      barrier disruption in Caco-2 monolayers. METHODS: The monolayers were exposed
      from the apical side to AcH +/- L-cysteine. Reactive oxygen species (ROS)
      generation and Snail activation were assessed by ELISA and immunofluorescence.
      Paracellular permeability, localization, and expression of ZO-1, occludin, E
      cadherin, and beta-catenin were examined using transepithelial electrical
      resistance (TEER), fluorescein isothiocyanate-labeled dextran 4 kDa (FITC-D4),
      immunofluorescence, and ELISA, respectively. Involvement of Snail was further
      addressed by inhibiting Snail using small interfering RNA (siRNA). RESULTS:
      Exposure to 25 MUM AcH increased ROS generation and ROS-dependently induced Snail
      phosphorylation. In addition, AcH increased paracellular permeability (decrease
      in TEER and increase in FITC-D4 permeation) in association with redistribution
      and decrease of TJ and AJ protein levels, which could be attenuated by L
      cysteine. Knockdown of Snail by siRNA attenuated the AcH-induced redistribution
      and decrease in the TJ and AJ proteins, in association with improvement of the
      barrier function. CONCLUSIONS: Our data demonstrate that oxidative stress
      mediated Snail phosphorylation is likely a novel mechanism contributing to the
      deleterious effects of AcH on the TJ and AJ, and intestinal barrier function.

PMID- 24033730
TI  - Evolving basilar artery stenosis with watershed ischemia.
AB  - Basilar artery stenosis where flow restriction constitutes the main
      pathomechanism are exceptional. Here, we report a case where the lesion
      progression was characterized by watershed infarct between the anterior inferior
      superior cerebellar arteries and deep pontine arteries, indicating a significant
      hemodynamic impairment. 

PMID- 24033731
TI  - Diagnostic evaluation of monoclonal gammopathy of undetermined significance.

PMID- 24033732
TI  - Actual and potential use of population viability analyses in recovery of plant
      species listed under the US endangered species act.
AB  - Use of population viability analyses (PVAs) in endangered species recovery
      planning has been met with both support and criticism. Previous reviews promote
      use of PVA for setting scientifically based, measurable, and objective recovery
      criteria and recommend improvements to increase the framework's utility. However,
      others have questioned the value of PVA models for setting recovery criteria and
      assert that PVAs are more appropriate for understanding relative trade-offs
      between alternative management actions. We reviewed 258 final recovery plans for
      642 plants listed under the U.S. Endangered Species Act to determine the number
      of plans that used or recommended PVA in recovery planning. We also reviewed 223
      publications that describe plant PVAs to assess how these models were designed
      and whether those designs reflected previous recommendations for improvement of
      PVAs. Twenty-four percent of listed species had recovery plans that used or
      recommended PVA. In publications, the typical model was a matrix population model
      parameterized with <=5 years of demographic data that did not consider
      stochasticity, genetics, density dependence, seed banks, vegetative reproduction,
      dormancy, threats, or management strategies. Population growth rates for
      different populations of the same species or for the same population at different
      points in time were often statistically different or varied by >10%. Therefore,
      PVAs parameterized with underlying vital rates that vary to this degree may not
      accurately predict recovery objectives across a species' entire distribution or
      over longer time scales. We assert that PVA, although an important tool as part
      of an adaptive-management program, can help to determine quantitative recovery
      criteria only if more long-term data sets that capture spatiotemporal variability
      in vital rates become available. Lacking this, there is a strong need for viable
      and comprehensive methods for determining quantitative, science-based recovery
      criteria for endangered species with minimal data availability. Uso Actual y
      Potencial del Analisis de Viabilidad Poblacional para la Recuperacion de Especies
      de Plantas Enlistadas en el Acta de Especies En Peligro de E.U.A. 

PMID- 24033734
TI  - Hypophosphatemia in patients with hepatitis B virus infection undergoing long
      term adefovir dipivoxil therapy.
AB  - AIM: The purpose of this study was to clarify the frequency of hypophosphatemia
      and other clinical features in patients with hepatitis B undergoing long-term
      therapy with adefovir dipivoxil (ADF). METHODS: Seventeen hepatitis B patients
      treated with a combination of lamivudine and ADF were analyzed. They were divided
      into two groups: patients who developed hypophosphatemia (P < 2.5 mg/dL) (group
      A) and those who did not (group B). The frequency of hypophosphatemia and other
      clinical features were retrospectively analyzed. RESULTS: There were six patients
      (35.3%) in group A. The treatment period was 57.3 +/- 15.6 and 61.8 +/- 25.7
      months in groups A and B, respectively. No differences were found between the
      groups prior to treatment. Among the six patients in group A, osteomalacia was
      observed in two, while a pathological fracture of the scapula was found in one.
      Decreases in phosphate (96 weeks after starting ADF), estimated glomerular
      filtration rate (eGFR) (48 weeks) and uric acid (24 weeks) levels, and increases
      in creatinine and alkaline phosphatase were noted in group A. CONCLUSION:
      Hypophosphatemia occurred in 35% of the patients under the long-term treatment
      with ADF. Although it was not possible to predict the decrease in phosphate
      before ADF therapy, decreases in uric acid and eGFR may be the early events
      relating to low phosphatemia.

PMID- 24033733
TI  - Side effects from oral opioids in older adults during the first week of treatment
      for acute musculoskeletal pain.
AB  - OBJECTIVES: The authors sought to describe the frequency of short-term side
      effects experienced by older adults initiating treatment with opioid-containing
      analgesics for acute musculoskeletal pain. METHODS: This was a cross-sectional
      study of individuals age 65 years or older initiating analgesic treatment
      following emergency department (ED) visits for acute musculoskeletal pain.
      Patients were called by phone 4 to 7 days after their ED visits to assess the
      intensity of six common opioid-related side effects using a 0 to 10 scale and to
      assess medication discontinuation due to side effects. Propensity score matching
      was used to compare side effects among patients initiating treatment with any
      opioid-containing analgesics to side effects among those initiating treatment
      with only nonopioids. RESULTS: Of 104 older patients initiating analgesic
      treatment following ED visits for musculoskeletal pain, 71 patients took opioid
      containing analgesics, 15 took acetaminophen, and 18 took ibuprofen. Among the
      patients who took opioids, at least one side effect of moderate or severe
      intensity (score >= 4) was reported by 62%. Among patients with matching
      propensity scores, those taking opioids were more likely to have had moderate or
      severe side effects than those taking only nonopioids (62%, 95% confidence
      interval [CI] = 48% to 74% vs. 4%, 95% CI = 1% to 20%) and were also more likely
      to have discontinued treatment due to side effects (16%, 95% CI = 8% to 29% vs.
      0%, 95% CI = 0% to 13%). The most common side effects due to opioids were
      tiredness, nausea, and constipation. CONCLUSIONS: Among older adults initiating
      treatment with opioid-containing analgesics for musculoskeletal pain, side
      effects were common and sometimes resulted in medication discontinuation.

PMID- 24033735
TI  - The role of the human leukocyte antigen system in retinopathy of prematurity: a
      pilot study.
AB  - AIM: To assess the association between the human leukocyte antigen system and
      retinopathy of prematurity. METHODS: Neonates of <32 weeks of gestational age,
      born at two level III neonatal intensive care units from January 2000 to December
      2001 and from January 2006 to June 2009, were included in the study. Demographic
      and clinical data were recorded, and retinopathy was classified according to the
      International Classification. Epithelial cells were collected from the oral
      cavity and the HLA were studied using the PCR/SSO method. Univariate and
      multivariate analyses were performed using SPSS(r) v.18. RESULTS: We evaluated
      156 neonates, including 82 (52.6%) males. Median gestational age was 29 (23-31)
      weeks, and median birth weight was 1030 (525-1935) grams. Seventy (44.9%) of the
      neonates developed retinopathy. Alleles HLA-B*38, HLA-Cw*12, HLA-DRB1*09, HLA
      DRB1*14 (univariate analysis) and HLA-A*68 and HLA-Cw*12 were associated to
      retinopathy (multivariate analysis). CONCLUSION: The results suggest that the HLA
      system may be associated with the development of retinopathy of prematurity. A
      large-scale population-based study should be performed to clarify this
      association.

PMID- 24033736
TI  - Effects of in vitro exposure to mercury on male gonads and sperm structure of the
      tropical fish tuvira Gymnotus carapo (L.).
AB  - This study investigated the progressive effects of HgCl2 in the testis and sperm
      of the tropical fish tuvira Gymnotus carapo L. exposed to increasing Hg
      concentrations (5-30 MUm) and increasing exposure times (24-96 h). Histopathology
      and metal concentrations in the testis were observed. Hg concentrations in the
      testis reached 5.1 and 5.2 MUg g(-1) in fish exposed to 20 and 30 MUm of Hg,
      respectively. Hg effects on testicular tissue were observed even at low Hg
      concentrations, with no alterations in gonadosomatic index. However, the
      quantitative analysis of the induced alterations (lesion index) demonstrated that
      the Hg effects in testis became more severe after exposure to higher
      concentrations (20 and 30 MUm) and during longer exposure (72 and 96 h), probably
      leading to partial or total loss of the organ function. Hg exposure (20 MUm) also
      affected sperm count and altered sperm morphology. This study showed that HgCl2
      caused progressive damage to testicular tissue, reduced sperm count and altered
      sperm morphology. These results are important in establishing a direct
      correlation between Hg accumulation and severity of lesions.

PMID- 24033737
TI  - A conceptual framework for cost management training in the Limpopo Province of
      South Africa.
AB  - AIMS: This paper describes the perceptions of nurse managers about their dual
      role in nursing units as cost centres. BACKGROUND: The tertiary hospital in the
      Limpopo province is the first institution to appoint nurse managers with a dual
      role in cost centres. The development of a conceptual framework for a context
      specific programme for Cost Centre Managers is the first of its nature in South
      Africa. METHOD: A qualitative, exploratory, descriptive design was followed. The
      target population included nurse managers (n = 35) formally appointed as cost
      centre managers with a dual role of delivering quality care and cost management.
      A focus group and individual interviews were conducted until data saturation
      occurred. RESULTS: Personal and professional distress, an empowering potential of
      being a cost centre manager, and the need for decentralized cost centre
      management were indicated as barriers for nurse managers that led to a framework
      for a context-specific training programme. CONCLUSION: There is a need for a
      context-specific training programme for cost centre managers in a hospital with
      cost centres. IMPLICATIONS FOR NURSING MANAGEMENT: The training of cost centre
      managers for their dual role in cost centres could enhance cost effectiveness,
      quality care and staff satisfaction.

PMID- 24033738
TI  - Risk-taking behaviours and beliefs about fertility in university students.
AB  - AIMS AND OBJECTIVES: To investigate the risk-taking behaviours and beliefs about
      fertility among university students in Turkey. BACKGROUND: Young people are
      usually ignorant about reproductive health and engage in risky practices. DESIGN:
      A descriptive cross-sectional study. METHODS: The convenience sample of the study
      was consisted of 1030 undergraduate students. Data were collected using a self
      administered question form, and students' reproductive health and lifestyle
      behaviours related with infertility, their beliefs about the risk factors and
      fertility myths were questioned. RESULTS: The mean age of the students was 20.4
      (SD = 2) and ranged between the ages of 16-37. Sexual activity rate was higher
      among men and 47% of men had more than one sexual partner. Condom use rate was
      low among women. Underweight was more common among women, while overweight was
      seen more among men. Students mostly did not exercise regularly. Alcohol was not
      common, and the rates of smoking were 15% and 23% for women and men,
      respectively. Only 35-50% of students thought that smoking, alcohol, stress,
      sexually transmitted diseases, infections, pollution, chemicals, radiation and
      cancer treatment could be risk factors for fertility. Advanced age and obesity
      were seen as risk factors for women. Of the students, 50-65% believed that having
      more than one sexual partner, being underweight, high-level exercise, excessive
      caffeine, chronic disease and medications could not have an effect on fertility.
      Women were more concerned about being infertile, and half of students believed
      that infertility is preventable. CONCLUSION: Turkish university students have
      insufficient knowledge of reproductive health, and they have false beliefs that
      might affect their risk perception or views about fertility. RELEVANCE TO
      CLINICAL PRACTICE: Reproductive healthcare services for young adults should be
      made more widespread and accessible, and nurses, health providers and instructors
      should be supportive of them in these matters.

PMID- 24033739
TI  - Understanding public perceptions of benefits and risks of childhood vaccinations
      in the United States.
AB  - In the face of a growing public health concern accompanying the reemerging threat
      of preventable diseases, this research seeks mainly to explain variations in the
      perceived benefits and risks of vaccinations among the general public in the
      United States. As Mary Douglas and Aaron Wildavsky's grid-group cultural theory
      of risk perception claims, the analytical results based upon original data from a
      nationwide Internet survey of 1,213 American adults conducted in 2010 suggest
      that individuals' cultural predispositions contribute to the formation of their
      perceptions pertaining to vaccine benefits and risks at both societal and
      individual levels, in conjunction with other factors suggested by previous risk
      perception literature, such as perceived prevalence of diseases, trust, knowledge
      level, and demographic characteristics. Those with a strong hierarch orientation
      tend to envision greater benefits and lesser risks and conceive of a relatively
      high ratio of benefit to risk when compared to other cultural types. By contrast,
      those with a strong fatalist tendency are inclined to emphasize risks and
      downplay benefits while conceiving of a low vaccination benefit-risk ratio.
      Situated between hierarchs and fatalists, strong egalitarians are prone to
      perceive greater benefits, smaller risks, and a more positive benefit-risk ratio
      than strong individualists. 

PMID- 24033740
TI  - Acquired uterine arteriovenous malformation developing in retained products of
      conception: a diagnostic dilemma.
AB  - Abnormal uterine bleeding in the postabortal period requires meticulous
      diagnostic work-up to decide proper management. Imaging modalities including
      Doppler sonography and magnetic resonance imaging in concert with clinical and
      laboratory findings are useful to narrow the differential diagnoses but are not
      definitive. Presence of increased uterine vascularity and arteriovenous shunting
      is non-specific and can be detected in a variety of conditions including retained
      trophoblastic tissue, gestational trophoblastic disease, arteriovenous
      malformation (AVM), placental polyp and vascular neoplasm. We present here a case
      of a multiparous woman with unexplained postabortal bleeding posing a diagnostic
      challenge. Excluding the possibility of AVM before attempting dilatation and
      curettage in such a clinical scenario is crucial to prevent catastrophic
      bleeding. 

PMID- 24033741
TI  - KPC-2 and OXA-48 carbapenemase-harbouring Enterobacteriaceae detected in an
      Austrian wastewater treatment plant.
AB  - Multiresistant Enterobacteriaceae, like carbapenemase-producing strains, have
      their primary reservoir in medical institutions. They can also be found with
      increasing tendency in other reservoirs. One possible way for entrance of
      multiresistant Enterobacteriaceae into the environment is via waste water. The
      aim of the study was to screen isolates from a wastewater treatment plant for the
      presence of carbapenemase-producing Enterobacteriaceae. Three isolates harboured
      carbapenemase genes, one Klebsiella pneumoniae harboured KPC-2 and one K.
      pneumoniae and one Escherichia coli harboured OXA-48. This is the first report of
      carbapenemase-harbouring Enterobacteriaceae isolated outside medical institutions
      in Austria and the first detection of KPC-harbouring K. pneumonia MLST ST 1245. 

PMID- 24033742
TI  - Evaluation of an oral health promotion program at the time of birth on dental
      caries in 5-year-old children in Vorarlberg, Austria.
AB  - OBJECTIVES: The aim of this study was to evaluate the effect of an early oral
      health promotion program (OHPP) on oral health of 5-year-old children in Austria
      by providing new mothers with dental health counseling. METHODS: Qualified dental
      health educators visited all mothers at time after birth in regional hospitals in
      Vorarlberg and counseled them regarding the oral health of their children as a
      one-off intervention. Mothers were given comprehensive oral hygiene instructions
      for their children and themselves (daily use of fluoride toothpaste, restoration
      of own caries lesions), which included practical tooth brush training and dietary
      counseling by the use of brief motivational interviewing and anticipatory
      guidance approaches. After 5 years, a case-cohort study was conducted to evaluate
      the program with annual dental check-ups of 471 children and a parent survey.
      Dental caries was scored using WHO diagnostic criteria at dentine level without
      radiography. To compare oral health parameters (dmfs/dmft, care index), children
      were allocated to intervention and control group and matched on basis of age,
      sex, ethnicity, and socio-economic status (SES) and analyzed statistically.
      RESULTS: Children whose mothers participated in the OHPP showed significantly
      lower caries prevalence and experience (33.2%; 3.2 +/- 7.4 d3-4 mfs/1.5 +/- 2.5
      d3-4 mft) than children whose mothers did not participate (42.6%; 5.2 +/- 6.4 d3
      4 mfs/2.4 +/- 4.1 d3-4 mft). Bivariate analysis showed that ethnicity, SES, age
      at which toothbrushing started, supervision of toothbrushing, use of fluoride
      salt, and use of fluoride toothpaste were significantly related to d3-4 mft.
      CONCLUSIONS: The OHPP was an effective community-based preventive approach for
      improving oral health in preschool children.

PMID- 24033744
TI  - Effect of short-chain fatty acids and acidification on the phasic and tonic motor
      activity of the human colon.
AB  - BACKGROUND: The effects of bacterial fermentation on human colonic motor activity
      could be explained by colonic acidification or short-chain fatty acid (SCFA)
      production. We compared in healthy volunteers the colonic motor effects of
      intracolonic infusion of neutral or acidic saline solutions and then of neutral
      or acidic solutions containing an SCFA mixture. METHODS: 20 healthy volunteers
      swallowed a probe (with an infusion catheter, 6 perfused catheters and a balloon
      connected to a barostat) that migrated into the colon. Colonic motor activity was
      recorded in fasting basal state (1 h), during (3 h) and after (2 h) intracolonic
      infusion in a random order on two consecutive days of 750 mL of NaCl at pH 7.0
      (neutral saline) or 4.5 (acidic saline) in 10 volunteers (first experiment) and
      of an SCFA mixture (acetic acid 66%, propionic acid 24% and butyric acid 10%; 100
      mM) at pH 7.0 or 4.5 in 10 other volunteers (second experiment). We determined
      for each hour a global motility index (reflecting phasic activity recorded by all
      catheters), the mean balloon volume (reflecting tonic activity), and the mean
      number of high-amplitude-propagated contractions (HAPCs). KEY RESULTS:
      Intracolonic infusion of neutral or acidic solutions containing saline or an SCFA
      mixture did not change the global motility index, the barostat balloon volume, or
      the HAPC number compared with basal values. CONCLUSIONS & INFERENCES: Under our
      experimental conditions, these findings suggest that the stimulation of colonic
      motor activity induced by carbohydrate fermentation is not explained by the
      acidification of the colonic contents or the resulting production of SCFAs.

PMID- 24033743
TI  - N-linked glycan profiling of GGTA1/CMAH knockout pigs identifies new potential
      carbohydrate xenoantigens.
AB  - BACKGROUND: The temporary or long-term xenotransplantation of pig organs into
      people would save thousands of lives each year if not for the robust human
      antibody response to pig carbohydrates. Genetically engineered pigs deficient in
      galactose alpha1,3 galactose (gene modified: GGTA1) and N-glycolylneuraminic acid
      (gene modified: CMAH) have significantly improved cell survival when challenged
      by human antibody and complement in vitro. There remains, however, a significant
      portion of human antibody binding. METHODS: To uncover additional xenoantigens,
      we compared the asparagine-linked (N-linked) glycome from serum proteins of
      humans, domestic pigs, GGTA1 knockout pigs, and GGTA1/CMAH knockout pigs using
      mass spectrometry. Carbohydrate structures were determined with assistance from
      GlycoWorkbench, Cartoonist, and SimGlycan software by comparison to existing
      database entries and collision-induced dissociation fragmentation data. RESULTS:
      Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS) analysis of reduced and solid-phase permethylated glycans resulted
      in the detection of high-mannose, hybrid, and complex type N-linked glycans in
      the 1000-4500 m/z ion range. GGTA1/CMAH knockout pig samples had increased
      relative amounts of high-mannose, incomplete, and xylosylated N-linked glycans.
      All pig samples had significantly higher amounts of core and possibly antennae
      fucosylation. CONCLUSIONS: We provide for the first time a comparison of the
      serum protein glycomes of the human, domestic pig, and genetically modified pigs
      important to xenotransplantation.

PMID- 24033745
TI  - Assessment of the craniocaudal stability of four extracapsular stabilization
      techniques during two cyclic loading protocols: a cadaver study.
AB  - OBJECTIVE: To (1) compare the effect of cyclic loading on craniocaudal tibial
      translation in cranial cruciate ligament (CrCL)-deficient stifles after
      extracapsular stabilization, and (2) evaluate the effect of peak force during
      cyclic loading on the rate of development of craniocaudal laxity. STUDY DESIGN:
      Biomechanical cadaveric study. SAMPLE POPULATION: Cadaveric pelvic limbs (n = 24
      pairs) from skeletally mature dogs. METHODS: Twenty-four pairs of stifles were
      randomly assigned to 4 stabilization groups: nylon leader lateral circumfabellar
      tibial suture (NLS); FiberTape lateral circumfabellar-tibial suture (FTLS);
      TightRope (TR); or bone anchor (BA). Contralateral limbs were cyclically loaded
      to produce cranial tibial translation at peak forces of either 80 or 160 N.
      Craniocaudal displacement of the tibia was measured with a mechanical testing
      machine during cyclic loading with the CrCL intact, after CrCL transection, and
      after extracapsular stabilization. The number of cycles each construct underwent
      before reaching 200% and 300% of the mean craniocaudal displacement present
      during cyclic loading of the CrCL-intact stifles was calculated. Number of cycles
      among treatment groups was compared with a Kruskal-Wallis test. P < .05 was
      considered significant. RESULTS: Mean +/- SD translation before and after CrCL
      transection were 3.9 +/- 0.6 and 14.6 +/- 1.7 mm, respectively. TR constructs
      resisted significantly more cycles than NLS constructs before reaching 7.8 mm
      (200%) and 11.7 mm (300%) of translation when loaded to 80 N. No other
      differences between constructs were significant at a peak load of 80 N. All
      constructs reached 7.8 and 11.7 mm of translation in fewer cycles when loaded to
      160 N than at 80 N. CONCLUSIONS: TR constructs were most resistant to elongation
      during cyclic loading. Doubling the peak force during cyclic loading
      significantly decreased the number of cycles constructs withstood, supporting
      recommendations for restricting postoperative activity after extracapsular
      stabilization of the CrCL-deficient stifle.

PMID- 24033746
TI  - Regulation of cell divisions and differentiation by MALE STERILITY32 is required
      for anther development in maize.
AB  - Male fertility in flowering plants relies on proper division and differentiation
      of cells in the anther, a process that gives rise to four somatic layers
      surrounding central germinal cells. The maize gene male sterility32 (ms32)
      encodes a basic helix-loop-helix (bHLH) transcription factor, which functions as
      an important regulator of both division and differentiation during anther
      development. After the four somatic cell layers are generated properly through
      successive periclinal divisions, in the ms32 mutant, tapetal precursor cells fail
      to differentiate, and, instead, undergo additional periclinal divisions to form
      extra layers of cells. These cells become vacuolated and expand, and lead to
      failure in pollen mother cell development. ms32 expression is specific to the pre
      meiotic anthers and is distributed initially broadly in the four lobes, but as
      the anther develops, its expression becomes restricted to the innermost somatic
      layer, the tapetum. The ms32-ref mac1-1 double mutant is unable to form tapetal
      precursors and also exhibits excessive somatic proliferation leading to numerous,
      disorganized cell layers, suggesting a synergistic interaction between ms32 and
      mac1. Altogether, our results show that MS32 is a major regulator in maize anther
      development that promotes tapetum differentiation and inhibits periclinal
      division once a tapetal cell is specified. 

PMID- 24033747
TI  - Hepatic ischemia reperfusion injury is associated with acute kidney injury
      following donation after brain death liver transplantation.
AB  - Donation after cardiac death liver transplant recipients have an increased
      frequency of acute kidney injury (AKI). This suggests that hepatic ischemia
      reperfusion injury may play a critical role in the pathogenesis of AKI after
      liver transplantation. The aim of this single-center study was to determine if
      hepatic ischemia-reperfusion injury, estimated by peak peri-operative serum amino
      transferase (AST), is associated with AKI following donation after brain death
      (DBD) liver transplantation. A total of 296 patients received 298 DBD liver
      transplants from January 2007 to June 2011. The incidence of AKI was 35.9%. AKI
      was a risk factor for chronic kidney disease (P = 0.037) and mortality (P =
      0.002). On univariate analysis, peak AST correlated with peak creatinine (P <
      0.001) and peak change in creatinine from baseline (P < 0.001). Peak AST was
      higher in AKI patients (P < 0.001). The incidence of AKI in patients with a peak
      AST of <1500, 1500-2999 and >= 3000 U/l was 26.1%, 39.8% and 71.2%, respectively
      (P < 0.001). On multiple logistic regression analysis, peak AST was independently
      associated with the development of AKI (P < 0.001). In conclusion, hepatic
      ischemia-reperfusion injury demonstrates a strong relationship with peri
      operative AKI in DBD liver transplant recipients.

PMID- 24033748
TI  - Music, musicians, medicine, and the kidney.
AB  - The relationship between music, medicine and nephrology is ancient; ranging from
      musicians afflicted with kidney disease, contributors to nephrology who were
      musicians, and the use of music to treat renal maladies. Musicians have long been
      afflicted by diseases of the kidney, particularly nephrolithiasis, for which
      Marin Marais in 1725 composed a unique piece for the viol detailing the harrowing
      experience of 'cutting for stone.' Beethoven and Mozart were afflicted by kidney
      disease, as are several current musicians. Where past musicians succumbed to
      their failing kidneys, the advent of renal replacement therapy has given today's
      musicians, such as James DePreist and Natalie Cole, the opportunity to continue
      performing and composing. Several notable physicians of old have excelled as
      musicians; one example is Jacob Henle (1809-1885), for whom the loop of Henle is
      named, another is Robert Christison, a contemporary of Richard Bright, who is
      considered a 'founder of nephrology'. Importantly, music therapy, as used in the
      times of Hippocrates and King David, has evolved from an empiric to a well
      established scientific discipline. Given the recent enlarging body of scholarly
      studies of music therapy, its rudimentary role in nephrology deserves further
      exploration. 

PMID- 24033750
TI  - Upregulation of tissue and urinary uroplakin mRNA in patients with vesicoureteral
      reflux.

PMID- 24033749
TI  - Effect of uracil addition on proteomic profiles and 1,3-beta-glucan production in
      Agrobacterium sp.
AB  - Uridine diphosphate (UDP)-glucose is a precursor of 1,3-beta-glucan and is
      synthesized from glucose-1-phosphate and uridine triphosphate (UTP). Uracil was
      used as a precursor for UTP, which resulted in an increase in both the UDP
      glucose level and the rate of 1,3-beta-glucan synthesis. 1,3-beta-Glucan
      production metabolism was reactivated after uracil addition during fermentation.
      2D-PAGE was used to examine the changes in the expression level of the key
      metabolic enzymes in the production of 1,3-beta-glucan after uracil addition. The
      results showed that the expression levels of UTP-glucose-1-phosphate
      uridylytransferase, phosphoglucomutase, and 1,3-beta-glucan synthase catalytic
      subunit, key metabolic enzymes in the curdlan biosynthesis pathway, were
      increased after uracil addition by 3.5%, 30%, and 35%, respectively. Uracil
      phosphoribosyltransferase, which converts uracil to uridine monophosphate (UMP),
      was also upregulated 79% more than that without uracil addition. However, the
      expression levels of orotidine 5-phosphate decarboxylase, glucose-1-phosphate
      adenylyltransferase, and glucose-6-phosphate isomerase were decreased after
      uracil addition. This proteomic information is useful for predicting changes in
      the pathway of uracil utilization. This work provides proteomic information for
      the integrative analysis of bioinformatic databases, which can be used to predict
      and understand the metabolism of glucan synthesis at the cellular level. 

PMID- 24033751
TI  - Age differences in the association of obstructive sleep apnea risk with cognition
      and quality of life.
AB  - Using a sample of 2925 stroke-free participants drawn from a national population
      based study, we examined cross-sectional associations of obstructive sleep apnea
      (OSA) risk with cognition and quality of life and whether these vary with age,
      while controlling for demographics and comorbidities. Included participants from
      the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were
      aged 47-93 years. OSA risk was categorized as high or low based on responses to
      the Berlin Sleep Questionnaire. Cognitive function was assessed with standardized
      fluency and recall measures. Depressive symptoms were assessed with the four-item
      Center for Epidemiologic Studies Depression Scale. Health-related quality of life
      (HRQoL) was assessed with the Medical Outcomes Study Short Form-12 (SF-12).
      Multivariate analyses of covariance (mancova) statistics were applied separately
      to the cognitive and quality of life dependent variables while accounting for
      potential confounders (demographics, comorbidities). In fully adjusted models,
      those at high risk for OSA had significantly lower cognitive scores (Wilks'
      lambda = 0.996, F3,2786  = 3.31, P < 0.05) and lower quality of life [depressive
      symptoms and HRQoL] (Wilks' lambda = 0.989, F3,2786  = 10.02, P < 0.0001).
      However, some of the associations were age-dependent. Differences in cognition
      and quality of life between those at high and low obstructive sleep apnea risk
      were most pronounced during middle age, with attenuated effects after age 70
      years. 

PMID- 24033752
TI  - Voxel-based morphometry of disproportionate cerebrospinal fluid space
      distribution for the differential diagnosis of idiopathic normal pressure
      hydrocephalus.
AB  - OBJECTIVE: To determine whether voxel-based morphometry of the cerebrospinal
      fluid (CSF) space can accurately differentiate iNPH from other related
      neurological disorders. METHODS: Nineteen patients with surgically proven iNPH
      and 24 patients with Alzheimer's disease (AD), 18 patients with Parkinson's
      disease (PD), and 14 healthy elderlies were examined. Regions of interest (ROIs)
      in the ventricular/sylvian (VS) and high convexity/midline (HCM) areas were used
      in VBM, and differences in CSF volume within these ROIs among the 4 groups were
      examined. RESULTS: The relative CSF volume in the VS-ROI in the iNPH group (.64)
      was significantly higher than that in the AD, PD, and healthy control groups
      (.26, .29, and .17, respectively; P < .001), whereas the relative CSF volume in
      the HCM-ROI was significantly reduced in the iNPH (.10) than in the other (.17,
      .16, and .16, respectively) groups (P < .001). Furthermore, the ratio of the 2
      areas (VS/HCM) was markedly higher in the iNPH (6.87) than in the other (1.65,
      1.74, .97, respectively) groups (P < .001), with sensitivity and specificity of
      .89 and 1.00, respectively. CONCLUSIONS: The VBM-based CSF space analysis can
      detect disproportionate changes in CSF space and differentiate iNPH patients from
      those with AD or PD and healthy elderlies accurately.

PMID- 24033753
TI  - Clinical experience of subcutaneous and transvenous implantable cardioverter
      defibrillators in children and teenagers.
AB  - BACKGROUND: Subcutaneous implantable cardioverter defibrillator (S-ICD) systems
      have no components in contact with the heart and may avoid complications such as
      lead fracture, venous obstruction, or endocarditis that occur with transvenous
      leads. Concerns have been raised regarding inappropriate shocks and pocket
      erosion with S-ICD systems. We have compared the performance of S-ICD and
      transvenous ICD systems in children and teenagers. METHODS: We studied
      consecutive patients <20 years of age who received an ICD over a 4-year period in
      two Scottish centers. Baseline characteristics, complications, and ICD therapy
      were recorded. The primary outcome measure was survival. The secondary outcome
      measure was survival-free from inappropriate ICD therapy or system revision.
      RESULTS: Nine S-ICD were implanted in nine patients. Eight transvenous ICD were
      implanted in six patients; two were redo procedures. Baseline characteristics
      were well matched. Median duration of follow-up was lower for S-ICD (20 months)
      than for transvenous ICD (36 months, P = 0.0262). Survival was 100% in both
      groups. Survival free of inappropriate therapy or system revision was 89% for S
      ICD and 25% for transvenous ICD systems (log-rank test, P = 0.0237). No S-ICD
      were extracted, but three transvenous ICD were extracted due to infection (n = 1)
      and lead failure (n = 2). CONCLUSIONS: In real-world use in children and
      teenagers, S-ICD may offer similar survival benefit to transvenous ICD, with a
      lower incidence of complications requiring reoperation. In the absence of
      randomized trials, S-ICD should be compared prospectively with transvenous ICD in
      large multicenter registries with comparable periods of follow-up.

PMID- 24033754
TI  - Sustained response to low-dose rituximab in idiopathic autoimmune hemolytic
      anemia.
AB  - OBJECTIVES: To evaluate the sustained response to low-dose (LD) rituximab in
      autoimmune hemolytic anemia (AIHA), the ex vivo effect on anti-RBC antibody
      production by mitogen-stimulated direct antiglobulin test (MS-DAT), and the in
      vitro dose effect of the drug on the production of anti-RBC antibodies. METHODS:
      Thirty two patients, 18 warm (W) AIHA and 14 cold hemagglutinin disease (CHD),
      were treated with LD rituximab (100 mg fixed dose *4 weekly infusions) along with
      a short course of oral prednisone. Complete clinical examination, blood counts,
      and hemolytic markers were performed at enrollment and at month 6, 12, 24, and
      36. RESULTS: Hematological parameters significantly improved at all time points
      compared to enrollment. The overall response was 90%, 100%, 100%, and 89% and the
      relapse-free survival 87%, 79%, 68%, and 68% at 6, 12, 24, and 36 months,
      respectively. Response rates were slightly better in WAIHA than in CHD, and
      relapse risk was greater in cold than warm forms (HR 2.1, 95% CI 0.6-7.9). Four
      patients were retreated (one patient twice), all achieving a response, lasting a
      median of 18 months (range 9-30). Treatment was well tolerated without adverse
      events or infections. Anti-RBC antibody production by MS-DAT significantly
      decreased over time. In vitro studies showed that rituximab effectively inhibited
      anti-RBC antibody production at 50 MUg/mL, 1/6 of the drug concentration after
      therapy with standard doses. CONCLUSIONS: These data confirm that LD rituximab
      treatment is effective and induces sustained responses in AIHA, and that a lower
      dose of the drug is enough to down-regulate autoantibody production.

PMID- 24033755
TI  - Prevalence of minimal hepatic encephalopathy and quality of life in patients with
      decompensated cirrhosis.
AB  - AIM: Minimal hepatic encephalopathy (MHE) affects more than 30% of patients with
      cirrhosis, and it has been suggested that despite no recognizable clinical
      symptoms of neurological abnormalities, it may affect health-related quality of
      life (HRQL); however, this fact remains controversial. The aim of our study was
      to evaluate the prevalence of MHE and HRQL in patients diagnosed with
      decompensated cirrhosis. METHODS: Patients with liver cirrhosis were selected
      independent of the etiology of the disease. All patients underwent a complete
      clinical history, and only patients with decompensated hepatic cirrhosis were
      included. Psychometric tests were applied to evaluate the presence of MHE along
      with the Chronic Liver Disease Questionnaire. Appetite was measured by verbal and
      visual analog scales. RESULTS: One hundred and twenty-five patients were included
      with a median age of 56.0 years. They were classified according to the Child-Pugh
      index as A, (n = 56), B, (n = 51) and C (n = 18). Prevalence of MHE was 44.0% (n
      = 55). In patients with MHE, a significant reduction was observed in domains of
      activity (3.3 [2.0] vs 4.8 [2.8]), fatigue (3.2 [2.0] vs 3.9 [2.3]), systemic
      symptoms (3.8 [2.0] vs 4.8 [1.7]), emotional function (3.6 [1.9] vs 4.0 [1.9])
      and global scoring (3.7 [1.7] vs 4.3 [1.8]) when compared with non-MHE patients
      (n = 70). Twenty-two percent of the patients with MHE reported little appetite
      compared with 11% in the non-MHE group. CONCLUSION: The results suggest that MHE
      and a reduction in appetite are associated with deterioration in HRQL in patients
      with decompensated cirrhosis.

PMID- 24033756
TI  - Raman spectrometric discrimination of flexirubin pigments from two genera of
      Bacteroidetes.
AB  - Flexirubins are specific polyene pigments produced by several genera of
      Bacteroidetes. Colonies and cell extracts of Flavobacterium johnsoniae and
      Flexibacter elegans have been investigated by Raman spectroscopy to show that
      this fast and non-destructive technique can be used to differentiate these
      pigments from carotenoids and to compare the flexirubin content of the two
      microorganisms. The presence or absence of certain distinguishing features in the
      CH combination band region at 2500-2750 cm(-1) can assist in the discrimination
      between the two flexirubins investigated. Raman spectroscopy is thus a suitable
      tool not only to detect flexirubin pigments in bacterial cells, but also to
      further characterize the pigments present in members of the Bacteroidetes genera
      that are rich in flexirubins.

PMID- 24033757
TI  - What do we learn from repeated population analyses?
AB  - Population analyses are performed on new and existing drugs. They play an
      important role in quantifying the time course of drug effects and provide a means
      of understanding the impact of variability between individuals on dosing
      requirements. For some drugs there have been several population analyses reported
      in the literature. It is important to understand how repeated population analyses
      can value add and what authors and readers can consider when reviewing such
      analyses. The purpose of this review is to explore what is learnt from repeated
      population analyses and provide an understanding of how the value-added nature of
      these analyses can be considered. 

PMID- 24033758
TI  - Application of relative real-time PCR to detect differential expression of
      virulence genes in Vibrio anguillarum under standard and stressed growth
      conditions.
AB  - In this study, we aimed to understand whether abiotic factors affect the
      expression of virulence genes in Vibrio anguillarum. We observed the in vitro
      responses of two Mediterranean strains of V. anguillarum to temperature, NaCl and
      iron concentration changes. We monitored growth performance and gene
      transcription levels by comparing the results obtained under stressed conditions
      (temperatures of 5  degrees C, 15  degrees C and 37  degrees C; NaCl
      concentrations of 3% and 5%; and iron depletion and excess) with those obtained
      under standard growth conditions (25  degrees C, 1.5% NaCl and 0.6 MUm of iron).
      The results showed that the strains respond differently. The strain 975/I was
      most strongly affected by conditions of 15  degrees C and iron depletion; these
      conditions induced increased transcription levels of empA, angR and fatA. Growth
      of the strain 17/I was inhibited at 15  degrees C and in iron depletion
      conditions; this strain also showed dramatic changes in the transcription levels
      of toxR and tonB2 under increased NaCl concentrations. These results demonstrate
      that environmental stress affects the expression of virulence genes in V.
      anguillarum that have implications for the competitiveness, stress tolerance and
      the ability of V. anguillarum to cause infection.

PMID- 24033759
TI  - Gastrointestinal: vomiting stones.

PMID- 24033760
TI  - Gastrointestinal: a rare cause of anal pain: gastric heterotopia of the rectum.

PMID- 24033761
TI  - Hepatobiliary and pancreatic: transient hepatic ischemia caused by acute portal
      vein thrombosis.

PMID- 24033763
TI  - High variability in the exposure of baclofen in alcohol-dependent patients.
AB  - BACKGROUND: Baclofen is a GABA-B receptor agonist used in the treatment of
      spasticity. Recently, baclofen is used out of its label to decrease craving of
      alcoholic patients. Its optimal use in these patients requires further
      pharmacokinetic information. The objective of this study was to characterize the
      pharmacokinetics of baclofen in alcohol-dependent patients. Randomized clinical
      trials are ongoing to evaluate the efficacy for this new indication. METHODS:
      Thirty-seven outpatients (weight: 74.0 kg [42.0 to 104.0]; age: 49 years [31 to
      68]) followed in the addictology unit were studied. Total mean dose of 77.9 mg
      (30 to 240) per day was administered by oral route. Therapeutic drug monitoring
      allowed the measurement of 139 plasma concentrations. The following covariates
      were evaluated: demographic data (age, body weight, height, sex), biological data
      (creatinine, urea, AST, ALT, albumin, PR, VGM, PAL, CDT, GGT), and tobacco
      consumption (number of cigarettes and Fagerstrom test). Pharmacokinetic analysis
      was performed by using a nonlinear mixed-effect population model (NONMEM 7.2
      software). RESULTS: Data were modeled with a 1-compartment pharmacokinetic model.
      The population typical mean (95% confidence interval [95% CI]) values for
      clearance (CL), apparent volume of distribution (V), and rate constant of
      absorption (Ka) were 9.9 l/h (9.0 to 11.1), 80.7 l (63.6 to 96.9), and 4.6/h (1.5
      to 19.9), respectively. The interindividual variability of CL (95% CI) and V (95%
      CI), and residual variability (95% CI) were 56.0% (47.9 to 60.7), 68.3% (48.7 to
      80.1), and 0.096 mg/l (0.079 to 0.107), respectively. CONCLUSIONS: Baclofen
      exhibited a linear pharmacokinetics with a proportional relationship from 30 to
      240 mg per day, the dose range currently used in alcoholic patients. A wide
      interpatient variability was observed which could not be explained by the
      covariates. This high variation of baclofen exposure may explain the lack of
      response observed for some patients.

PMID- 24033762
TI  - Contribution of hydrogen sulfide to the control of coronary blood flow.
AB  - OBJECTIVE: This study examined the mechanisms by which H2 S modulates coronary
      microvascular resistance and myocardial perfusion at rest and in response to
      cardiac ischemia. METHODS: Experiments were conducted in isolated coronary
      arteries and in open-chest anesthetized dogs. RESULTS: We found that the H2 S
      substrate l-cysteine (1-10 mM) did not alter coronary tone of isolated arteries
      in vitro or coronary blood flow in vivo. In contrast, intracoronary (ic) H2 S
      (0.1-3 mM) increased coronary flow from 0.49 +/- 0.08 to 2.65 +/- 0.13 mL/min/g
      (p < 0.001). This increase in flow was unaffected by inhibition of Kv channels
      with 4-aminopyridine (p = 0.127) but was attenuated (0.23 +/- 0.02-1.13 +/- 0.13
      mL/min/g) by the KATP channel antagonist glibenclamide (p < 0.001). Inhibition of
      NO synthesis (l-NAME) did not attenuate coronary responses to H2 S.
      Immunohistochemistry revealed expression of CSE, an endogenous H2 S enzyme, in
      myocardium. Inhibition of CSE with beta-cyano-l-alanine (10 MUM) had no effect on
      baseline coronary flow or responses to a 15-second coronary occlusion (p = 0.82).
      CONCLUSIONS: These findings demonstrate that exogenous H2 S induces potent,
      endothelial-independent dilation of the coronary microcirculation predominantly
      through the activation of KATP channels, however, our data do not support a
      functional role for endogenous H2 S in the regulation of coronary microvascular
      resistance.

PMID- 24033764
TI  - Guidelines for the treatment of pneumonia and urinary tract infections:
      evaluation of methodological quality using the Appraisal of Guidelines, Research
      and Evaluation II instrument.
AB  - Reliance on evidence-based medicine requires high methodological standards from
      guideline developers. We sought to determine the methodological quality of
      guidelines on pneumonia and urinary tract infections (UTIs). We included
      guidelines published by national or international committees in the last 10 years
      providing recommendations for antibiotic type or duration. We applied the
      Appraisal of Guidelines for Research and Evaluation II checklist, adding under
      each item the specific focus relevant to bacterial infections, addressing
      antibiotic resistance and local epidemiology. Three assessors scored each
      guideline independently. Mean aggregated scores, converted to percentage per
      domain, are presented. We included 13 guidelines on the treatment of pneumonia
      and seven guidelines for the treatment of UTI. 'Scope and purpose' scored 69.4%
      for pneumonia and 71.4% for UTI. Guidelines were downgraded for lack of an
      epidemiological overview relevant to intended users. 'Stakeholder involvement'
      scored 39.5% for pneumonia and 44.5% UTI, with the major fault being lack of
      patient consultation. 'Rigour of development' scored 42.8% for pneumonia and
      56.9% for UTI. Commonly, the search process lacked precision, no risk of bias
      assessment was performed, outcomes in primary studies were not critically
      assessed or used to direct recommendations, and there was no formal methodology
      for formulating recommendations. 'Clarity of presentation' scored highest: 67.7%
      for pneumonia and 68.5% for UTI. 'Applicability' of the guidelines in antibiotic
      stewardship programmes was usually not addressed: 16.9% and 25.4%, respectively.
      'Editorial independence' scored 30.6% for pneumonia and 55.6% for UTI. Formal
      examination of guidelines in infectious diseases showed worrying findings related
      to core methodology and potential bias caused by competing interests.

PMID- 24033765
TI  - Visual fatigue effects on vergence dynamics in asymptomatic individuals.
AB  - PURPOSE: To evaluate objectively changes in vergence dynamics following
      intentional visual fatiguing tasks using congruent (C) and non-congruent (NC)
      vergence stimulus demands. METHODS: Pre- and post-task vergence dynamics to a
      10.3 degrees  disparity stimulus were recorded objectively in 12 adult,
      asymptomatic individuals for both convergence and divergence. There were two
      fatigue-inducing tasks: Congruent or C-task: Subjects altered bifixation (50
      cycles) between reduced Snellen charts at 2 m and at 20 cm every 3 s. Non
      congruent or NC task: Subjects performed 50 cycles of vergence flipper (7Delta
      BO/BI), while bifixating a reduced Snellen chart at 40 cm. Pre- and post-task
      mean amplitude, time constant, peak velocity, and steady-state response
      variability were compared. RESULTS: There was a significant increase in mean post
      task, steady-state response variability for both the C and NC tasks. However,
      there were no significant group differences for either convergence or divergence
      between the pre- and post-mean amplitude, time constant, and peak velocity
      parameters for both the C and NC tasks, although post-task peak velocity was
      consistently reduced. CONCLUSIONS: Steady-state vergence response variability was
      found to be the critical objective parameter to demonstrate significant fatigue
      effects in the group. Peak velocity was also consistently reduced to a small
      extent in the NC task. We speculate that these fatigue effects are of a central,
      and not of peripheral, origin.

PMID- 24033766
TI  - Comparison of cortical thickness in patients with early-stage versus late-stage
      amnestic mild cognitive impairment.
AB  - BACKGROUND AND PURPOSE: Disappointing outcomes from clinical trials involving
      amyloid-modifying therapies for Alzheimer's disease (AD) have prompted more focus
      on the concept of early-stage (E) amnestic mild cognitive impairment (E-aMCI).
      However, limited evidence suggests that E-aMCI may represent aMCI at a very early
      stage of AD. Furthermore, the nature of the progression of E-aMCI to late-stage
      aMCI (L-aMCI) remains unclear. Therefore, the aim of the present study was to
      characterize patterns of cortical thinning in both E-aMCI and L-aMCI patients.
      METHODS: Cortical thicknesses were measured in 190 patients with aMCI and 147
      subjects with normal cognition. In accordance with memory test scores involving
      delayed recall items, aMCI patients were divided into two subgroups, containing
      73 E-aMCI subjects with milder memory impairment [scores between -1.5 standard
      deviation (SD) and -1.0 SD compared with age- and education-matched norms] and
      117 L-aMCI subjects with more severe memory impairment (scores lower than -1.5
      SD). RESULTS: Compared with controls, the E-aMCI group exhibited cortical
      thinning in the left medial temporal and insular regions, whereas the L-aMCI
      group showed cortical thinning in widespread regions, including the bilateral
      dorsolateral prefrontal, anterior and medial temporal, and temporo-parietal
      association cortices, and the precuneus. When the two aMCI groups were directly
      compared, the L-aMCI group showed greater cortical thinning in the right superior
      prefrontal, medial temporal, posterior cingulate and lateral parietal cortices.
      CONCLUSION: Our findings suggest that E-aMCI might represent an early symptomatic
      stage of AD. Furthermore, L-aMCI might resemble AD more closely than E-aMCI, in
      terms of the topography of cortical thinning.

PMID- 24033767
TI  - Googling trends in conservation biology.
AB  - Web-crawling approaches, that is, automated programs data mining the internet to
      obtain information about a particular process, have recently been proposed for
      monitoring early signs of ecosystem degradation or for establishing crop
      calendars. However, lack of a clear conceptual and methodological framework has
      prevented the development of such approaches within the field of conservation
      biology. Our objective was to illustrate how Google Trends, a freely accessible
      web-crawling engine, can be used to track changes in timing of biological
      processes, spatial distribution of invasive species, and level of public
      awareness about key conservation issues. Google Trends returns the number of
      internet searches that were made for a keyword in a given region of the world
      over a defined period. Using data retrieved online for 13 countries, we exemplify
      how Google Trends can be used to study the timing of biological processes, such
      as the seasonal recurrence of pollen release or mosquito outbreaks across a
      latitudinal gradient. We mapped the spatial extent of results from Google Trends
      for 5 invasive species in the United States and found geographic patterns in
      invasions that are consistent with their coarse-grained distribution at state
      levels. From 2004 through 2012, Google Trends showed that the level of public
      interest and awareness about conservation issues related to ecosystem services,
      biodiversity, and climate change increased, decreased, and followed both trends,
      respectively. Finally, to further the development of research approaches at the
      interface of conservation biology, collective knowledge, and environmental
      management, we developed an algorithm that allows the rapid retrieval of Google
      Trends data. 

PMID- 24033768
TI  - Clinical peptidomic analysis by a one-step direct transfer technology: its
      potential utility for monitoring of pathophysiological status in female
      reproductive system disorders.
AB  - To date, numerous studies have searched for candidate molecules or clinical
      examination methods as potential biomarkers for monitoring intractable diseases,
      such as carcinomas. Evidence accumulated over the past decade shows that many
      proteolytic peptides appear in human humoral fluids, including peripheral blood,
      in association with an individual's health condition. Although an analysis of the
      whole peptide (the 'peptidome') using mass spectrometry is thought to be one of
      the most powerful and promising experimental approaches, it has failed to
      identify biomarkers in the clinical blood samples, presumably due to the
      methodological limitations. In general, commonly used techniques for proteomic
      analysis of blood require the removal of large amounts of serum/plasma proteins
      prior to mass spectrometry analysis, and this step seems to have resulted in the
      overlooking of important biomarkers during the analytical process. Here, we
      provide a brief overview of a new quantitative peptidomic analysis by a one-step
      direct transfer technology without depletion of major blood proteins. Using this
      technology, we herein report experimental data on serum peptidomic analysis for
      patients with pregnancy-induced hypertension as a clinical model. In addition, we
      refer to the potential utility of this approach for the monitoring of
      pathophysiological status in female reproductive system disorders in general. 

PMID- 24033769
TI  - Literature review: preoperative radiotherapy and rectal cancer - impact on acute
      symptom presentation and quality of life.
AB  - AIMS AND OBJECTIVES: This paper presents a critical review of published
      literature detailing side effects of preoperative radiotherapy in patients with
      rectal cancer and the impact of their treatment on their quality of life which
      will assist in guiding nursing management in the future. BACKGROUND: Preoperative
      radiotherapy for rectal cancer leads to a number of side effects that have a
      negative influence on patients' quality of life. Although studies have
      investigated the various adverse effects that can occur, these have not yet been
      critically appraised and synopsised to form a comprehensive review of their
      prevalence and effects on the quality of life of patients with rectal cancer.
      DESIGN: This literature review study addresses the aims and objectives. METHODS:
      Following a literature search of electronic databases, 23 articles were retrieved
      that met the selection criteria with papers discussed in relation to symptoms
      that present due to this treatment, with six of these 23 studies also referring
      to health-related quality of life. RESULTS: Preoperative radiotherapy leads to a
      number of common adverse effects including diarrhoea, dermatological problems,
      micturition problems, fatigue, sexual dysfunction and pain. Some can lead to a
      decline in quality of life during treatment and cause prolonged surgical recovery
      times, but there appears to be no long-term deterioration in quality of life.
      CONCLUSIONS: There is a paucity of literature that specifically examines fatigue
      and quality of life in relation to patients with rectal cancer during
      preoperative radiotherapy treatment. RELEVANCE TO CLINICAL PRACTICE: Awareness of
      the prevalence and severity of the acute side effects of preoperative
      radiotherapy will enable nurses to thoroughly assess these symptoms, plan and
      implement appropriate interventions and evaluate outcomes. This will assist in
      optimising the quality of life of patients with rectal cancer and may hasten
      postoperative recovery times.

PMID- 24033770
TI  - Effect of postoperative xylazine administration on cardiopulmonary function and
      recovery quality after isoflurane anesthesia in horses.
AB  - OBJECTIVE: To evaluate equine cardiopulmonary function and recovery quality after
      administration of 0.25 or 0.50 mg/kg xylazine intravenously (IV) during recovery.
      STUDY DESIGN: Randomized, blinded, prospective, clinical study. ANIMALS: Horses
      (n = 20). METHODS: During recovery after 3 hours of isoflurane anesthesia for
      arthroscopic surgery, horses were administered either 0.25 mg/kg (G25, n = 10) or
      0.50 mg/kg (G50, n = 10) xylazine intravenously. Vital signs and arterial blood
      samples were obtained during recovery before sedation (baseline), 5, 10, 20, 30,
      and 45 minutes after xylazine and 30 minutes after standing. The quality of
      recovery scores ranged from 10 to 72 (10 = best, 72 = worst). RESULTS: G25 horses
      recovered faster (mean +/- SD, 33 +/- 5 min) than G50 horses (50 +/- 7 min, P <
      .0001). Mean maximal decrease in arterial oxygen tension was 55 +/- 11 mmHg in
      G25 (at 10 minutes; P < .05) and 54 +/- 7 mmHg in G50 (at 20 minutes; P < .01).
      G25 group had a total recovery score (23 [range 18-29]) and number of attempts to
      stand (4 +/- 2) greater than the G50 group (18 [10-23] and 1 +/- 1, respectively;
      P < .001). CONCLUSIONS: Both doses of xylazine promoted a moderate and transient
      hypoxemia during recovery; however, the 0.5 mg/kg dose produced a longer and
      improved quality of recovery from anesthesia.

PMID- 24033771
TI  - The perfectly motivated nurse and the others: workplace and personal
      characteristics impact preference of nursing tasks.
AB  - AIMS: To identify whether motivation of nurses coincides with personal values,
      workplace or personal characteristics. BACKGROUND: Shortage of nursing workforce
      compromises patient care. Motivation and job satisfaction are factors considered
      to make nurses quit. Little is known about measurement and variation of nurses'
      motivation. Funding for human resource programmes is limited - effective
      programmes could focus on nurses in need of motivational support. METHODS:
      Exploratory study with nurses using questionnaires in an academic hospital in
      Germany. Work motivation was approximated through preference of nursing tasks.
      Questionnaires measured personal values, preference of generic nursing tasks, and
      workplace and personal characteristics. RESULTS: A total of 212 questionnaires
      were usable. Higher motivation was found in groups of nurses with the dominant
      personal value 'Benevolence', with high self-rated expertise, in the middle of
      their career or working in surgical or general wards. Motivation was low in
      nurses with the dominant value 'Hedonism', or nurses in internal medicine or with
      low to medium self-rated expertise or who used computers infrequently.
      CONCLUSIONS: Motivation coincided with dominant personal values, workplace and
      personal characteristics. The results should be validated in other settings.
      IMPLICATIONS FOR NURSING MANAGEMENT: Human resource programmes could focus on
      nurses whose motivation is at risk. Prospectively highly motivated individuals
      should be hired with priority.

PMID- 24033772
TI  - Cranio-caudal (transradial) approach for renal artery intervention.
AB  - This report describes the technique of transradial renal angiography and
      interventions. We illustrate the approach using typical case images. We believe
      cranio-caudal approach to the renal artery for diagnostic and therapeutic
      catheterization offers advantages over the traditional femoral approach.

PMID- 24033773
TI  - The inflammatory response in blood and in remote organs following acute kidney
      injury.
AB  - In patients with acute kidney injury (AKI) mortality remains high, despite the
      fact that the patients are treated with continuous renal replacement therapy. The
      interaction between the kidney and the immune system might explain the high
      mortality observed in AKI. In order to elucidate the interaction between the
      kidney and immune system we developed a two-hit model of AKI and endotoxemia. Our
      hypothesis was that ischemia/reperfusion (I/R) of the kidney simultaneously with
      endotoxemia would generate a more extensive inflammatory response compared to I/R
      of the hind legs. Our expectation was that elevated levels of cytokines would be
      found in both blood and in organs distant to the kidneys. Forty mice were divided
      into five groups. The mice were subjected to the following operations: A: Sham
      only, no lipopolysaccharide (LPS); B: I/R of both kidneys + LPS; C: LPS only; D:
      Nephrectomy + LPS; E: I/R of both hind legs + LPS. In groups B and E, I/R times
      were identical. All mice were kept alive for 24 h and then sacrificed. Levels of
      interleukin (IL)-1beta, IL-6, IL-10, and tumor necrosis factor-alpha were
      measured in the blood. The activity of myeloperoxidase (MPO) in lungs, kidneys,
      and liver was evaluated as an indirect measurement of accumulation of
      granulocytes. In this study, significantly higher amount of IL-6 and IL-10 in the
      plasma was observed following renal I/R compared to hind leg I/R. The elevated
      levels of cytokine in plasma were observed following nephrectomy and endotoxemia.
      The neutrophil infiltration of distant organs measured by the levels of MPO in
      the lung and liver also showed a significantly higher level in renal I/R compared
      to hind leg I/R. Renal I/R is associated with a more pronounced inflammatory
      response in blood and distant organs. The high cytokine levels measured following
      nephrectomy might be explained by compromised elimination of cytokines by the
      kidney in AKI.

PMID- 24033774
TI  - Regenerative treatment of male stress urinary incontinence by periurethral
      injection of autologous adipose-derived regenerative cells: 1-year outcomes in 11
      patients.
AB  - OBJECTIVES: To assess the efficacy and safety of a novel cell therapy for male
      stress urinary incontinence consisting of periurethral injection of autologous
      adipose-derived regenerative cells, and to determine the 1-year outcomes.
      METHODS: A total of 11 male patients with persistent stress urinary incontinence
      after prostate surgery were included in the study. The Celution system was used
      to isolate adipose-derived regenerative cells from abdominal adipose tissue
      obtained by liposuction. Subsequently, these regenerative cells, and a mixture of
      regenerative cells and adipose tissue were transurethrally injected into the
      rhabdosphincter and submucosal space of the urethra, respectively. The 1-year
      outcomes were assessed using a 24-h pad test, a validated patient questionnaire,
      urethral pressure profile, transrectal ultrasonography and magnetic resonance
      imaging. RESULTS: Stress urinary incontinence improved progressively in eight
      patients during the 1-year follow up, as determined by a 59.8% decrease in the
      leakage volume in the 24-h pad test, decreased frequency and amount of
      incontinence, and improved quality of life. One patient achieved total
      continence. The mean maximum urethral closing pressure and functional profile
      length increased from 35.5 to 44.7 cmH2O, and from 20.4 to 26.0 mm, respectively.
      Magnetic resonance imaging showed the sustained presence of the injected adipose
      tissue, and enhanced ultrasonography showed a progressive increase in blood flow
      to the injected area in all patients. No significant adverse events were observed
      peri- or postoperatively. CONCLUSION: Periurethral injection of autologous
      adipose-derived regenerative cells might represent a safe and feasible treatment
      modality for male stress urinary incontinence.

PMID- 24033775
TI  - Tidal volume and minute ventilation parameters derived from pacemaker impedance
      measurements can predict experimental heart failure development.
AB  - BACKGROUND: Specific respiratory patterns and periodic breathing have been
      associated with heart failure. Less is known regarding changes in tidal volume
      (TV) and minute ventilation (MV) as a result of early heart failure (HF)
      decompensation. METHODS AND RESULTS: Twelve adult Yucatan minipigs were implanted
      with a biventricular pacemaker and a left ventricular pressure sensor. HF was
      induced using high-rate pacing at 240 paces per minute for 2-4 weeks, followed by
      2 weeks of recovery. Left ventricular pressure measurements and weekly
      echocardiograms verified the development of HF. The right and left ventricular
      intrathoracic impedance (RVITI and LVITI, respectively) signals were used to
      determine the respiratory parameters of rate, TV, and MV. Compared to baseline
      (BL), during HF, the TV dropped 68% for RVITI and 61% for LVITI (P < 0.0001 for
      both). Correspondingly, MV dropped 34% for RVITI and 27% for LVITI (P < 0.0001
      for both). The daily medians of the respiratory rate (RR) and the longest breath
      interval (LBI) did not change significantly from BL to HF and recovery. However,
      circadian variation of the RR and the LBI became blunted during HF development.
      All derived respiratory parameters showed the reverse trend during the recovery
      period. CONCLUSION: TV and MV change independently from the RR in early HF
      decompensation. Tracking the changes of TV and MV with an implantable device may
      provide an additional method for early HF detection and assessment of the
      response to therapy.

PMID- 24033776
TI  - Identification of active oxalotrophic bacteria by Bromodeoxyuridine DNA labeling
      in a microcosm soil experiments.
AB  - The oxalate-carbonate pathway (OCP) leads to a potential carbon sink in
      terrestrial environments. This process is linked to the activity of oxalotrophic
      bacteria. Although isolation and molecular characterizations are used to study
      oxalotrophic bacteria, these approaches do not give information on the active
      oxalotrophs present in soil undergoing the OCP. The aim of this study was to
      assess the diversity of active oxalotrophic bacteria in soil microcosms using the
      Bromodeoxyuridine (BrdU) DNA labeling technique. Soil was collected near an
      oxalogenic tree (Milicia excelsa). Different concentrations of calcium oxalate
      (0.5%, 1%, and 4% w/w) were added to the soil microcosms and compared with an
      untreated control. After 12 days of incubation, a maximal pH of 7.7 was measured
      for microcosms with oxalate (initial pH 6.4). At this time point, a DGGE profile
      of the frc gene was performed from BrdU-labeled soil DNA and unlabeled soil DNA.
      Actinobacteria (Streptomyces- and Kribbella-like sequences), Gammaproteobacteria
      and Betaproteobacteria were found as the main active oxalotrophic bacterial
      groups. This study highlights the relevance of Actinobacteria as members of the
      active bacterial community and the identification of novel uncultured
      oxalotrophic groups (i.e. Kribbella) active in soils.

PMID- 24033777
TI  - Lost in translation.

PMID- 24033778
TI  - Lost indeed, but not in translation.

PMID- 24033779
TI  - Commentary on Subbaraman et al. (2013) [corrected]: cravings as a mediator and
      moderator of drinking outcomes in the COMBINE Study.

PMID- 24033780
TI  - Commentary on Kuntsche & Labhart (2013): when and why does pre-gaming occur?

PMID- 24033781
TI  - Commentary on Derringer et al. (2013): more evidence for a unidimensional
      framework for substance use disorders.

PMID- 24033782
TI  - Commentary on Ling et al. (2013): is there a role for psychotherapy in the
      treatment of opioid dependence?

PMID- 24033783
TI  - Contrasting calcium localization and speciation in leaves of the Medicago
      truncatula mutant cod5 analyzed via synchrotron X-ray techniques.
AB  - Oxalate-producing plants accumulate calcium oxalate crystals (CaOx(c)) in the
      range of 3-80% w/w of their dry weight, reducing calcium (Ca) bioavailability.
      The calcium oxalate deficient 5 (cod5) mutant of Medicago truncatula has been
      previously shown to contain similar Ca concentrations to wild-type (WT) plants,
      but lower oxalate and CaOx(c) concentrations. We imaged the Ca distribution in WT
      and cod5 leaflets via synchrotron X-ray fluorescence mapping (SXRF). We observed
      a difference in the Ca distribution between cod5 and WT leaflets, manifested as
      an abundance of Ca in the interveinal areas and a lack of Ca along the secondary
      veins in cod5, i.e. the opposite of what is observed in WT. X-ray
      microdiffraction (MUXRD) of M. truncatula leaves confirmed that crystalline
      CaOx(c) (whewellite; CaC2 O4 . H2 O) was present in the WT only, in cells
      sheathing the secondary veins. Together with MUXRD, microbeam Ca K-edge X-ray
      absorption near-edge structure spectroscopy (MUXANES) indicated that, among the
      forms of CaOx, i.e. crystalline or amorphous, only amorphous CaOx was present in
      cod5. These results demonstrate that deletion of COD5 changes both Ca
      localization and the form of CaOx within leaflets.

PMID- 24033784
TI  - Thermal stability and activity improvements of a Ca-independent alpha-amylase
      from Bacillus subtilis CN7 by C-terminal truncation and hexahistidine-tag fusion.
AB  - Simultaneous improvements of thermostability and activity of a Ca-independent
      alpha-amylase from Bacillus subtilis CN7 were achieved by C-terminal truncation
      and his6-tag fusion. C-terminal truncation, which eliminates C-terminal 194-amino
      acid residues from the intact mature alpha-amylase, raised the turnover number by
      35% and increased the thermostability in terms of half-life at 65  degrees C by
      threefold. A his6-tag fusion at either the C- or N-terminus of truncated alpha
      amylase further enhanced its turnover number by 59% and 37%, respectively.
      Molecular modeling revealed that these improvements could be attributed to
      structural rearrangement and reorientation of the catalytic residues.

PMID- 24033785
TI  - Solid-surface vitrification and in-straw dilution after warming of in vitro
      produced bovine embryos.
AB  - Three experiments were designed to test a solid-surface vitrification system for
      bovine in vitro-produced embryos and to develop a simple method of in-straw
      dilution after warming, which can be potentially used for direct transfer in the
      field. Experiment 1 evaluated embryo survival rates (i.e. re-expansion and
      hatching) after vitrification and warming in three different solutions: VS1 (20%
      ethylene glycol (EG) + 20% propanediol (PROH) + 0.25 m trehalose (Tr)), VS2 (20%
      EG + 1M Tr) or VS3 (30% EG + 0.75 m Tr). Re-expansion and hatching rates were
      higher (p < 0.05) for embryos vitrified in VS3 (72.2 +/- 1.9 and 58.2 +/- 0.8)
      than VS1 (64.4 +/- 0.9 and 37.2 +/- 2.5) or VS2 (68.5 +/- 1.5 and 49.6 +/- 1.0; p
      < 0.05). Experiment 2 was designed to compare two methods of vitrification: glass
      micropipettes or solid surface, using the VS1 or VS3 solutions. No significant
      differences were detected between the two methods; but re-expansion and hatching
      rates were higher (p < 0.05) with VS3 (73.5 +/- 3.1 and 47.1 +/- 2.1) than VS1
      (63.3 +/- 3.3 and 39.7 +/- 2.8). In experiment 3, embryos were vitrified by solid
      surface in VS1 or VS3 solutions and cryoprotectants were diluted in-straw after
      warming in a TCM 199, 0.25 m sucrose solution or holding media. Survival rates of
      embryos vitrified in VS3 did not differ between those exposed to 0.25 m sucrose
      (74.7 +/- 1.3 and 57.2 +/- 2.2) or holding (77.3 +/- 1.4 and 58.0 +/- 2.5) medium
      after warming; however, survival rates of embryos vitrified in VS1 were higher (p
      < 0.05) in those exposed to 0.25 m sucrose (67.7 +/- 2.3 and 47.0 +/- 1.7) than
      holding medium (54.5 +/- 1.0 and 27.7 +/- 3.1). In conclusion, solid-surface
      vitrification using simplified EG-based solutions and in-straw dilution with
      holding media may be a practical alternative for cryopreservation and direct
      transfer of in vitro-produced bovine embryos. 

PMID- 24033786
TI  - Targeted hepatitis C screening among ex-injection drug users in the community.
AB  - BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is one of the
      leading causes of cirrhosis and hepatocellular carcinoma worldwide. It is highly
      prevalent among injection drug users (IDUs) but is often undiagnosed because they
      represent an underprivileged group that faces multiple barriers to medical care.
      Here, we report the results of the New Life New Liver Project, which provides
      targeted HCV screening and education for ex-IDUs in the community. METHODS:
      Patients were recruited through the social worker networks and referrals by
      fellow ex-IDUs, and rapid diagnosis was based on point-of-care anti-HCV testing
      at rehabilitation centers. RESULTS: From 2009 to 2012, we served 234 subjects.
      One hundred thirty (56%) subjects were anti-HCV positive. The number needed to
      screen to detect one patient with positive anti-HCV was 1.8 (95% confidence
      interval, 1.6-2.0). However, only 69 (53%) HCV patients attended subsequent
      follow-up at regional hospitals, and 26 (20%) received antiviral therapy.
      Patients who attended follow-up were older, had higher education level and more
      active disease as evidenced by higher alanine aminotransferase, HCV RNA, and
      liver stiffness measurement by transient elastography. CONCLUSIONS: Targeted
      screening in ex-IDUs is effective in identifying patients with HCV infection in
      the community. Improvement in the referral system and introduction of interferon
      free regimens are needed to increase treatment uptake.

PMID- 24033787
TI  - Combining the 'bottom up' and 'top down' approaches in pharmacokinetic modelling:
      fitting PBPK models to observed clinical data.
AB  - Pharmacokinetic models range from being entirely exploratory and empirical, to
      semi-mechanistic and ultimately complex physiologically based pharmacokinetic
      (PBPK) models. This choice is conditional on the modelling purpose as well as the
      amount and quality of the available data. The main advantage of PBPK models is
      that they can be used to extrapolate outside the studied population and
      experimental conditions. The trade-off for this advantage is a complex system of
      differential equations with a considerable number of model parameters. When these
      parameters cannot be informed from in vitro or in silico experiments they are
      usually optimized with respect to observed clinical data. Parameter estimation in
      complex models is a challenging task associated with many methodological issues
      which are discussed here with specific recommendations. Concepts such as
      structural and practical identifiability are described with regards to PBPK
      modelling and the value of experimental design and sensitivity analyses is
      sketched out. Parameter estimation approaches are discussed, while we also
      highlight the importance of not neglecting the covariance structure between model
      parameters and the uncertainty and population variability that is associated with
      them. Finally the possibility of using model order reduction techniques and
      minimal semi-mechanistic models that retain the physiological-mechanistic nature
      only in the parts of the model which are relevant to the desired modelling
      purpose is emphasized. Careful attention to all the above issues allows us to
      integrate successfully information from in vitro or in silico experiments
      together with information deriving from observed clinical data and develop
      mechanistically sound models with clinical relevance. 

PMID- 24033788
TI  - Prevalence of computed tomographic subchondral bone lesions in the scapulohumeral
      joint of 32 immature dogs with thoracic limb lameness.
AB  - Osteochondrosis is a common developmental abnormality affecting the subchondral
      bone of immature, large breed dogs. The purpose of this retrospective study was
      to describe CT lesions detected in scapulohumeral joints of 32 immature dogs
      undergoing CT for thoracic limb lameness. Eight dogs (14 scapulohumeral joints)
      had arthroscopy following imaging. Thirteen dogs (19 scapulohumeral joints) were
      found to have CT lesions, including 10 dogs (16 scapulohumeral joints) with
      subchondral bone lesions and 3 dogs with enthesopathy of the supraspinatus
      tendon. In one dog, subchondral bone lesions appeared as large oval defects
      within the mid-aspect of the glenoid cavities, bilaterally. These lesions
      resembled osseous cyst-like lesions commonly identified in the horse. This is the
      first report of such a presentation of a subchondral bone lesion in the glenoid
      cavity of a dog. In all dogs, small, focal, round or linear lucent defects were
      visible within the cortical bone at the junction of the greater tubercle and
      intertubercular groove. These structures were thought to represent vascular
      channels. Findings from this study support the use of CT as an adjunct modality
      for the identification and characterization of scapulohumeral subchondral bone
      lesions in immature dogs with thoracic limb lameness. 

PMID- 24033789
TI  - Shaping and remodeling of the fetoplacental circulation: aspects of health and
      disease.
AB  - Extensive vascular adaptations occur during pregnancy, and these result in the
      formation of a low-resistance placental circulation that maintains high blood
      flow to the developing fetus. These adaptations encompass both functional and
      structural alterations, including altered vasoreactivity of resistance vessels,
      arterial remodeling and angiogenesis. This Special Topics issue presents a
      collection of expert reviews that summarize the current state of knowledge on the
      regulation of the structural and functional changes that occur within the
      fetoplacental circulation, as well as introduce emerging research questions and
      tools. Emphasis is placed on defining the mechanisms that underlie these
      physiological adaptations, as a foundation for applying this knowledge to the
      development of improved early detection markers and treatments for pathological
      conditions such as preeclampsia, gestational diabetes mellitus, and fetal growth
      restriction. 

PMID- 24033790
TI  - Liver-specific deceased donor risk indices.
AB  - In order to assess the quality of the donor liver, procuring surgeons should
      accurately evaluate not only general donor risk indices, such as donor age,
      causes of brain death and cold ischemic time, but also consider the specific
      donor risk indices. In this review, we focus on liver-specific deceased donor
      risk indices, including liver steatosis, anti-hepatitis B core (HBc) positive or
      hepatitis C virus (HCV) positive donors, hypernatremia and anatomical variations.
      Liver steatosis is strongly associated with poor graft function after liver
      transplantation. Liver with more than 40-50% macrosteatosis should not be used.
      However, at present the quantity of fatty livers lack accepted standards. The
      computerized image analysis programs should be used to automate the determination
      of fat content in liver biopsy specimens. Liver grafts from anti-HBc positive
      donors can be safely used, preferentially in hepatitis B surface antigen (HBsAg)
      positive or anti-HBc/anti-HBs positive recipients. HCV positive allografts free
      from fibrosis or severe inflammation are a safe option for HCV positive
      recipients. The procurement team should consider liver biopsy to evaluate these
      HCV positive allografts. Donor serum sodium over 150 mm may predict a higher rate
      of graft primary non-functions. Recently, however, some investigators reported
      the sodium level likely has little clinical impact on post-transplant liver
      function. The incidence of hepatic artery variations has been reported to be
      approximately 30%. To avoid injuries, it is very important to know and identify
      these variations with precision at the time of organ procurement. 

PMID- 24033791
TI  - Development of a selective and differential medium for capsulated Lactococcus
      garvieae.
AB  - A selective and differential medium termed 'LG agar' was developed for the
      isolation and presumptive identification of Lactococcus garvieae that results in
      black colonies with red halos. In this study, all 14 strains of L. garvieae and
      only 9 of the 148 strains representing 38 other species were able to grow on the
      LG agar. The nine viable strains on LG agar plates (including Enterococcus
      faecalis, Enterococcus faecium, Lactococcus lactis, Vibrio fluvialis, Vibrio
      furnissii, Vibrio mimicus and Vibrio salmonicida) were further differentiated
      from L. garvieae by various colours or colony features. Colonies isolated from
      the mixing culture and the infected giant sea perch using LG agar plates were all
      positively identified as L. garvieae by conventional tests and 16S rDNA
      sequencing. Furthermore, LG agar discriminated capsulated strains of L. garvieae,
      which were believed to be correlated with pathogens of fish and shellfish, from
      non-capsulated ones by colony appearances. The specificity and differentiating
      ability of LG agar suggest that this medium displays considerable potential for
      primary isolation and presumptive identification of L. garvieae from pathological
      and environmental samples.

PMID- 24033792
TI  - Ultraviolet radiation and nanoparticle induced intracellular free radicals
      generation measured in human keratinocytes by electron paramagnetic resonance
      spectroscopy.
AB  - BACKGROUND: Several nanoparticle-based formulations used in cosmetics and
      dermatology are exposed to sunlight once applied to the skin. Therefore, it is
      important to study possible synergistic effects of nanoparticles and ultraviolet
      radiation. METHODS: Electron paramagnetic resonance spectroscopy (EPR) was used
      to detect intracellular free radicals induced by ultraviolet B (UVB) radiation
      and amorphous silica nanoparticle and to evaluate the influence of nanoparticle
      surface chemistry on particle cytotoxicity toward HaCaT cells. Uncoated titanium
      dioxide nanoparticles served as positive control. In addition, particle
      intracellular uptake, viability, and induction of interleukin-6 were measured.
      RESULTS: We found that photo-activated titanium dioxide particles induced a
      significant amount of intracellular free radicals. On the contrary, no
      intracellular free radicals were generated by the investigated silica
      nanoparticles in the dark as well as under UVB radiation. However, under UVB
      exposure, the non-functionalized silica nanoparticles altered the release of IL
      6. At the same concentrations, the amino-functionalized silica nanoparticles had
      no influence on UVB-induced IL-6 release. CONCLUSION: EPR spectroscopy is a
      useful technique to measure nanoparticle-induced intracellular free radicals. Non
      toxic concentrations of silica particles enhanced the toxicity of UVB radiation.
      This synergistic effect was not mediated by particle-generated free radicals and
      correlated with particle surface charge and intracellular distribution.

PMID- 24033793
TI  - Mycobacterium leprae DNA in peripheral blood may indicate a bacilli migration
      route and high-risk for leprosy onset.
AB  - Leprosy epidemiological studies have been restricted to Mycobacterium leprae DNA
      detection in nasal and oral mucosa samples with scarce literature on peripheral
      blood. We present the largest study applying quantitative real-time PCR (qPCR)
      for the detection of M. leprae DNA in peripheral blood samples of 200 untreated
      leprosy patients and 826 household contacts, with results associated with
      clinical and laboratory parameters. To detect M. leprae DNA a TaqMan qPCR assay
      targeting the M. leprae ML0024 genomic region was performed. The ML0024 qPCR in
      blood samples detected the presence of bacillus DNA in 22.0% (44/200) of the
      leprosy patients: 23.2% (16/69) in paucibacillary (PB), and 21.4% (28/131) in
      multibacillary (MB) patients. Overall positivity among contacts was 1.2%
      (10/826), with similar percentages regardless of whether the index case was PB or
      MB. After a follow-up period of 7 years, 26 contacts have developed leprosy.
      Comparing the results of healthy contacts with those that become ill, ML0024 qPCR
      positivity at the time of diagnosis of their index case represented an impressive
      14.78-fold greater risk for leprosy onset (95% CI 3.6-60.8; p <0.0001). In brief,
      contacts with positive PCR in blood at diagnosis of index cases are at higher
      risk of later leprosy onset and this marker might be combined with other
      prognostic markers for management of contacts, which requires further studies.

PMID- 24033794
TI  - Development and preliminary validation of a questionnaire on regular exercise
      beliefs among patients with chronic obstructive pulmonary disease.
AB  - AIMS AND OBJECTIVES: To develop a Regular Exercise Belief Questionnaire and test
      its psychometric properties for patients with chronic obstructive pulmonary
      disease. BACKGROUND: Regular exercise has been shown to significantly improve
      physical capacity and the quality of life of patients with chronic obstructive
      pulmonary disease. However, their adherence to long-term exercise is low. To
      develop an effective strategy for promoting good exercise behaviours, it is
      important to have a validated instrument to evaluate factors related to engaging
      in exercise. DESIGN AND METHODS: A cross-sectional design was used for the study.
      Construction of the Regular Exercise Belief Questionnaire was based on the Theory
      of Planned Behaviour Reliability and validity were assessed using a sample of 136
      male patients with chronic obstructive pulmonary disease. The construct validity
      of the questionnaire was confirmed through exploratory factor analysis and known
      group technique. RESULTS: Exploratory factor analysis resulted in an eight-factor
      solution that explained 70.4% of the total variance. The internal consistency of
      the Regular Exercise Belief Questionnaire was 0.83-0.93. The Regular Exercise
      Belief Questionnaire was preliminarily found to be reliable and exhibited
      satisfactory validity for patients with chronic obstructive pulmonary disease.
      CONCLUSION: The Regular Exercise Belief Questionnaire is the first theory-based
      measure of exercise beliefs among patients with chronic obstructive pulmonary
      disease. The questionnaire provides an effective method to examine behaviour
      beliefs, normative beliefs and control beliefs about regular exercise. CLINICAL
      RELEVANCE: The measure can be used to periodically evaluate the exercise beliefs
      in clinics and to examine the effectiveness of exercise programmes in patients
      with chronic obstructive pulmonary disease. The result of the evaluation could
      also apply to identify strategies related to promoting exercise behaviours.

PMID- 24033796
TI  - Evaluation of percutaneously adjustable hydraulic urethral sphincters with and
      without induced mechanical failure.
AB  - OBJECTIVE: To describe (1) the radiographic appearance of intact hydraulic
      urethral sphincters (HUS) and (2) the success of leak detection using clinically
      feasible methods. STUDY DESIGN: Prospective, blinded in vitro study. SAMPLE
      POPULATION: Thirty HUS devices (10 each of 8, 10, and 12 mm diameter sizes).
      MATERIALS AND METHODS: All devices were inflated with saline (0.9% NaCl) solution
      to complete occlusion, inspected, and weighed over a 24-hour period for
      manufacturing defects. HUS phantoms were created to mimic surrounding soft
      tissues. One randomly selected HUS of each size was evaluated radiographically at
      different inflation volumes and angles. All HUS systems were then evaluated in
      random order before and after puncture with volumetry, manometry, radiography,
      and contrast fluoroscopy. Volumetry was the total volume (mL) retrieved from each
      HUS system. Manometry was the pressure (cm H2 O) within each HUS system. The HUS
      devices were filled to a known volume before each measurement. RESULTS: When all
      HUS sizes were considered, volumetry did not reveal significant differences
      before and after puncture, but manometry was significantly different (P < .001).
      Radiography was 63.8% sensitive and 88.3% specific for puncture diagnosis, with
      inter-observer agreement of 0.58. Contrast fluoroscopy was 78.4% sensitive and
      100% specific, with inter-observer agreement of 0.97. CONCLUSIONS: Of those
      methods tested, contrast fluoroscopy was the most sensitive, specific, and
      consistent method of leak detection. Manometry was also helpful, but may be
      difficult to use clinically. Volumetry and radiography were relatively poor
      indicators of leakage in this model.

PMID- 24033795
TI  - Is there a one-way street from essential tremor to Parkinson's disease? Possible
      biological ramifications.
AB  - There is considerable evidence for an association between essential tremor (ET)
      and Parkinson's disease (PD), although the topic remains somewhat controversial.
      An important issue, not previously addressed, is what seems to be the
      unidirectional nature of the relationship (ET->ET + PD and not PD->PD + ET). The
      aims of this review are (i) to discuss the evidence for and against a
      unidirectional relationship and (ii) to discuss the implications of such a
      unidirectional relationship, if it exists, for disease mechanisms. Evidence 'for'
      a unidirectional relationship includes (i) abundant clinical anecdotal
      observation and (ii) clinical and epidemiological studies. Evidence 'against' is
      theoretical rather than empirical. Overall, the evidence 'for' is stronger,
      although additional studies are needed in order to be certain; for the time
      being, it might be best to leave this as an open question. The biological
      ramifications/extensions of such a unidirectional relationship include (i) that
      the association is causal (i.e., some aspect of ET pathophysiology predisposes an
      individual to develop PD) and (ii) that some ET cases may have a circumscribed
      form of Lewy body disease, and the secondary development of PD may represent a
      spread of those Lewy bodies in the brainstem. The presence and nature of the
      links between ET and PD are controversial. Further primary data (epidemiological
      and pathological) are needed to improve understanding of the relationship and its
      implications for the pathogenesis of both disorders.

PMID- 24033797
TI  - Ecological sustainability as the fourth landmark in the development of
      conservation ethics.
AB  - Aldo Leopold, in "The Land Ethic," made 2 important contributions to conservation
      ethics: he emphasized the community and ecosystem levels of organization and he
      explicitly included people as members of the biotic community. Leopold's writings
      remain eloquent, inspirational, and influential, but the ideas he describes are
      inherently complex, and ecological science has continued to evolve since "The
      Land Ethic" was published in 1949. We used 4 sets of quotations from Leopold's
      essays to develop our commentary on the meaning of and challenges in interpreting
      his work and to explore the ongoing development of conservation ethics: the "A-B
      cleavage" (Leopold's description of the contrast between utilitarian value versus
      a broader definition of value in nature), "land health" and the rightness of
      human action, the right of all species to continued existence in natural
      populations "at least in spots," and humans as "plain member[s] and citizen[s]"
      of the "land-community." We define the broader function of land and land health
      in "The Land Ethic" as including completeness, dynamic stability, and self
      renewal in a way that incorporates the needs of humans and all other species. We
      argue that the consequences of implementing Leopold's land ethic include multiple
      conservation goals nested within an overall systems approach and that
      conservation science must clarify the implications of Leopold's ethic by
      quantitatively investigating and defining large-scale, system-level ecological
      sustainability. At this scale, land use will encompass areas ranging from large
      expanses of wilderness to areas dominated by humans.

PMID- 24033798
TI  - The American Society for Veterinary Clinical Pathology Regulatory Affairs
      Committee's clinical pathology best practices recommendations will impact the
      discipline of veterinary toxicologic clinical pathology.

PMID- 24033799
TI  - Magic mirror on the wall, who is the fairest of them all?: you, my Queen, are
      fairest of all!

PMID- 24033800
TI  - Skunk musk causes methemoglobin and Heinz body formation in vitro.
AB  - BACKGROUND: A captive Red Panda developed a regenerative anemia with Heinz bodies
      after being sprayed by a skunk. A definite cause-and-effect relationship between
      skunk musk and oxidative erythrocyte damage has not been reported, but it was
      suspected in one reported case of a dog with Heinz body hemolytic anemia.
      OBJECTIVE: The objective was to determine whether skunk musk induces oxidative
      HGB damage in vitro. METHODS: Plasma and RBC were harvested from heparinized
      blood of 3 dogs, 3 cats, and a Red Panda. Skunk musk was solubilized in ethanol
      and mixed with plasma from each species to make stock solutions of 4% musk and 4%
      ethanol. Aliquots of RBC were resuspended in autologous stock solutions and
      solvent controls to yield musk concentrations of 0%, 0.04%, and 0.4% (by volume).
      Aliquots were incubated at 37 degrees C for 4-72 hours and assessed for oxidative
      damage by visual inspection, optical absorbance spectroscopy, transmission
      electron microscopy, and light microscopy after Wright and vital New Methylene
      Blue staining. RESULTS: Dose-dependent brown color and absorption changes
      characteristic of methemoglobin were present by 4 hours and increased over 24
      hours (Red Panda) and 72 hours (dog and cat). Similarly, there were time
      dependent (all species) and dose-dependent (dog and cat) increases in the number
      of Heinz bodies, which were present by 4 hours and numerous by 24 hours.
      CONCLUSIONS: In vitro, skunk musk causes Heinz body and methemoglobin formation
      in canine, feline, and Red Panda RBC, supporting the clinical association between
      Heinz body hemolytic anemia and skunk spray exposure.

PMID- 24033801
TI  - Markers of iron metabolism in retired racing Greyhounds with and without
      osteosarcoma.
AB  - BACKGROUND: Greyhounds have well-described clinicopathologic idiosyncrasies,
      including a high prevalence of osteosarcoma (OSA). Hematocrit, HGB, and HGB
      oxygen affinity are higher than in other dogs, while haptoglobin concentration is
      lower, so we hypothesized that Greyhounds have a different iron metabolism. To
      our knowledge, there are no reports on serum iron profiles in Greyhounds.
      OBJECTIVES: To elucidate iron metabolism in Greyhounds, we wanted to compare
      serum iron concentration, total iron-binding capacity (TIBC), and percent
      transferrin saturation (%SAT) in healthy retired racing Greyhounds (RRGs) with
      OSA (RRGs - OSA), and also with non-Greyhounds (NGs), without and with OSA (NGs -
      OSA). METHODS: Serum iron concentration and unsaturated iron-binding capacity
      (UIBC) were measured by standard methods, and TIBC and %SAT were calculated in
      RRGs (n = 25), RRGs - OSA (n = 28), NGs (n = 30), and NGs - OSA (n = 32).
      RESULTS: TIBC was lower in RRGs than in NGs (P < .0001), and in RRGs - OSA than
      in NGs - OSA (P < .0001). NGs - OSA had lower TIBC than healthy NGs (P = .003).
      Percent SAT was higher in RRGs than in NGs (P < .0001) and in RRGs - OSA (P =
      .008), and %SAT was also lower in NGs than in NGs - OSA (P = .004). Percent SAT
      was also higher in RRGs - OSA than in NGs - OSA (P = .001). Both RRGs - OSA (P =
      .02) and NGs - OSA (P < .0001) had lower serum iron concentrations than their
      healthy counterparts. CONCLUSION: Lower TIBC and higher %SAT may constitute
      another Greyhound idiosyncrasy compared with other dogs. In this study, all dogs
      with OSA had higher serum iron concentrations and %SAT than healthy dogs.

PMID- 24033802
TI  - Pelvic magnetic resonance imaging in the ewe: a model for experimental
      gynecologic research.
AB  - AIM: Our goal was to demonstrate the feasibility of pelvic magnetic resonance
      imaging (MRI) in the ewe. MATERIAL AND METHODS: Two ewes underwent a pelvic 3
      Tesla MRI scan, under light anesthesia, with T2-weighted fast spin-echo images
      and T1-weighted spoiled gradient-echo images. Multiplan T1 weighted images were
      also obtained after the intravenous injection of a contrast product. One ewe was
      anestrous and the other one had undergone ovarian stimulation. RESULTS: No
      incident occurred during the examination. Both the uterus (with two horns) and
      the ovaries were identified. The intensity of the endometrial, myometrial and
      ovarian signals was similar to that encountered in women. The uterus and ovaries
      could be enhanced in both cases. Pelvic vasculature was also studied. In the case
      of hormonal stimulation, the endometrium was thicker, follicular growth was
      identified and enhancement seemed greater. CONCLUSION: MRI in the ewe is feasible
      and could be helpful in experimental gynecologic research, especially in uterus
      transplantation.

PMID- 24033803
TI  - Molecular characterization and antibiotic resistance of clinical isolates of
      methicillin-resistant Staphylococcus aureus obtained from Southeast of Iran
      (Kerman).
AB  - Staphylococcus aureus infections, particularly infections caused by methicillin
      resistant S. aureus (MRSA) strains, are emerging as a major public health
      problem. The aim of this study was to determine the prevalence of MRSA,
      antibiotic resistance profile and staphylococcal cassette chromosome mec (SCCmec)
      type of MRSA isolates obtained from clinical samples. Totally, 162 S. aureus
      isolates were obtained from clinical samples at three university hospitals in
      Kerman, Iran from March 2011 to February 2012. All isolates were identified as S.
      aureus by phenotypic methods and confirmed by PCR amplification of the nuc gene.
      MRSA isolates were screened by phenotypic tests and confirmed by presence of mecA
      gene. The minimum inhibitory concentrations (MICs) of the MRSA isolates against
      antibacterial agents were determined by E-test. All isolates were analyzed by PCR
      for the presence of mecA and pvl genes. SCCmec typing of MRSA isolates was
      performed by multiplex PCR assay. Strain typing was carried out with REP-PCR.
      Using mecA gene PCR and phenotypic methods, 56.8% of the isolates were identified
      as MRSA. All MRSA isolates were susceptible to vancomycin and linezolid. The
      sensitivity of MRSA isolates to trimethoprim-sulfamethoxazole, clindamycin,
      ciprofloxacin, gentamicin, and erythromycin was 70.66, 66.53, 42.4, 38.05, and
      29.35%, respectively. The most frequent SCCmec types were type III (48.31%)
      followed by type V (19.1%), type I (16.85%), and type IV (3.37%). The pvl gene
      was detected in 3.08% of isolates (two MRSA and three MSSA isolates). REP-PCR
      typing divided the 92 MRSA isolates into 10 distinct clusters. Our results
      indicate that vancomycin and linezolid are the most effective antibacterial
      agents against MRSA isolates and SCCmec type III is predominant in MRSA strains
      in this area.

PMID- 24033804
TI  - The Arabidopsis calmodulin-like protein, CML39, functions during early seedling
      establishment.
AB  - During Ca(2+) signal transduction, Ca(2+)-binding proteins known as Ca(2+)
      sensors function to decode stimulus-specific Ca(2+) signals into downstream
      responses. Plants possess extended families of unique Ca(2+) sensors termed
      calmodulin-like proteins (CMLs) whose cellular roles are not well understood.
      CML39 encodes a predicted Ca(2+) sensor whose expression is strongly increased in
      response to diverse external stimuli. In the present study, we explored the
      biochemical properties of recombinant CML39, and used a reverse genetics approach
      to investigate its physiological role. Our data indicate that Ca(2+) binding by
      CML39 induces a conformational change in the protein that results in an increase
      in exposed-surface hydrophobicity, a property that is consistent with its
      predicted function as a Ca(2+) sensor. Loss-of-function cml39 mutants resemble
      wild-type plants under normal growth conditions but exhibit persistent arrest at
      the seedling stage if grown in the absence of sucrose or other metabolizable
      carbon sources. Under short-day conditions, cml39 mutants display increased
      sucrose-induced hypocotyl elongation. When grown in the dark, cml39 mutants show
      impaired hypocotyl elongation in the absence of sucrose. Promoter-reporter data
      indicate that CML39 expression is prominent in the apical hook in dark-grown
      seedlings. Collectively, our data suggest that CML39 functions in Arabidopsis as
      a Ca(2+) sensor that plays an important role in the transduction of light signals
      that promote seedling establishment.

PMID- 24033805
TI  - The chicken-wing morphology: an anatomical challenge for left atrial appendage
      occlusion.
AB  - OBJECTIVES: To describe the particular assessment and closure strategy that was
      followed in patients with left atrial appendages (LAA) with an early and severe
      bend. BACKGROUND: The presence of a chicken-wing morphology with an early and
      severe bend constitutes one of the most difficult anatomical settings for
      transcatheter LAA occlusion. METHODS: Between November 2009 and December 2012,
      patients who presented chicken-wing LAA with an early (<20 mm from the ostium)
      and severe bend (<180 degrees ) were identified and included in the analysis. A
      particular implanting strategy consisting of deploying the distal lobe of the
      device inside the chicken-wing bend was used in all cases. RESULTS: Among 42
      patients who underwent LAA occlusion during the study period, 5 (12%) presented
      the pre-specified anatomy. Following the mentioned implanting strategy, all
      patients underwent successful LAA occlusion using the Amplatzer Cardiac Plug (n =
      2) and the Amplatzer Amulet (n = 3). Successful occlusion was achieved in all
      patients. None of them presented any procedural complication. Follow-up
      transesophageal echocardiography at 3 months showed successful LAA sealing in all
      patients and no device embolization or thrombosis. CONCLUSIONS: According to our
      results, the pre-specified closing implantation technique for chicken-wing LAAs
      with an early and severe bend might be a valid strategy for this challenging
      anatomical setting. Further cases will be necessary to confirm the results.

PMID- 24033806
TI  - Temporal stability in the spectral representation of complex fractionated atrial
      electrograms.
AB  - BACKGROUND: Although local electrograms during atrial fibrillation (AF) are often
      spectrally analyzed over 8-second (8s) intervals, changes may be common over
      intervals as short as 2s. We sought to determine whether averaged 2s measurements
      of electrogram spectral parameters were similar to 8s measurements, and whether
      the 2s intervals could provide an estimate of the temporal stability of the
      signal frequency content in paroxysmal versus persistent AF. METHODS: Complex
      fractionated atrial electrograms (CFAEs) were acquired outside the pulmonary vein
      ostia and from free wall sites in nine paroxysmal and 10 longstanding persistent
      AF patients. Using a 2s sliding calculation window, a frequency spectrum was
      computed every 100 ms over an interval of 8.4 seconds (82 spectra in total). The
      dominant frequency (DF), the dominant amplitude (DA), and the mean spectral
      profile (MP) were measured. The 2s measurements were compared to single 8.4
      second interval measurements. Coefficients of variation (COV) were computed from
      the 82 spectra for each CFAE recording to determine temporal variability of
      parameters. RESULTS: Over the sliding 2s computation intervals, as for fixed 8.4
      second computation intervals, mean DA and DF were significantly higher in
      longstanding persistent AF while MP was significantly higher in paroxysmal AF (P
      <= 0.001). The COV was significantly higher for the DF parameter in paroxysmal AF
      (P < 0.001) and significantly higher for the MP parameter in persistent AF (P <
      0.02). CONCLUSIONS: For both paroxysmal and persistent AF data, the 2s sliding
      window averages provide similar results to single 8.4-second intervals, and
      information regarding temporal stability was additionally obtained in the
      process.

PMID- 24033807
TI  - Exposure to workplace bullying and post-traumatic stress disorder symptomology:
      the role of protective psychological resources.
AB  - AIM: To examine the relationship between nurses' exposure to workplace bullying
      and Post-Traumatic Stress Disorder symptomology and the protective role of
      psychological capital (PsyCap). BACKGROUND: Workplace bullying has serious
      organisational and health effects in nursing. Few studies have examined the
      relation of workplace bullying to serious mental health outcomes, such as Post
      Traumatic Stress Disorder. Even fewer have examined the effect of intrapersonal
      strengths on the health impact of workplace bullying. METHOD: A survey of 1205
      hospital nurses was conducted to test the hypothesized model. Nurses completed
      standardized measures of bullying, Post-Traumatic Stress Disorder and PsyCap.
      RESULT: A moderated regression analysis revealed that more frequent exposure to
      workplace bullying was significantly related to Post-Traumatic Stress Disorder
      symptomology regardless of the PsyCap level. That is, PsyCap did not moderate the
      bullying/PTSD relationship in either group. Bullying exposure and PsyCap were
      significant independent predictors of Post-Traumatic Stress Disorder symptoms in
      both groups. Efficacy, a subdimension of PsyCap, moderated the bullying/Post
      Traumatic Stress Disorder relationship only among experienced nurses. CONCLUSION:
      Workplace bullying appears to be predictive of Post-Traumatic Stress Disorder
      symptomology, a serious mental health outcome. IMPLICATIONS FOR NURSING
      MANAGEMENT: Workplace bullying is a serious threat to nurses' health and calls
      for programmes that eliminate bullying and encourage greater levels of positive
      resources among nurses.

PMID- 24033808
TI  - Invasion of rhizobial infection thread by non-rhizobia for colonization of Vigna
      radiata root nodules.
AB  - Legumes develop symbiotic relationships with Rhizobium by a complex exchange of
      signals. Despite the high specificity between symbiotic partners, the presence of
      non-rhizobial bacteria in root nodules has been reported. To investigate how
      these rhizobacteria enter root nodules, fluorescently tagged Pseudomonas
      fluorescens and Klebsiella pneumoniae were co-inoculated with host-nodulating
      Ensifer adhaerens to Vigna radiata seedlings and root hair infection was
      monitored using confocal microscopy at 5 days post inoculation. Pseudomonas
      fluorescens and K. pneumoniae invaded the root hair only when co-inoculated with
      E. adhaerens. Recovery of inoculated tagged strains and confirmation through CLSM
      and 16S rRNA gene sequencing confirmed that the test rhizobacteria occupied
      nodules. We hereby report with the help of confocal microscopy that rhizobacteria
      migrate along the length of host-nodulating rhizobial strain and become localized
      in root nodules. We further report isolation of eight non-rhizobial bacterial
      genera, predominantly Bacillus spp. and Paenibacillus spp., from nodules of field
      grown V. radiata. 

PMID- 24033809
TI  - Survival after nephroureterectomy for upper tract urothelial carcinoma: a
      population-based competing-risks analysis.
AB  - OBJECTIVES: To examine the rates of cancer-specific mortality, other-cause and
      bladder cancer mortality in patients with upper-tract urothelial carcinoma
      undergoing radical nephroureterectomy. METHODS: Relying on the Surveillance,
      Epidemiology, and End Results database, 9899 patients treated with radical
      nephroureterectomy were identified. A 20-strata graphical aid was constructed
      using age (<60, 60-69, 70-79, >79 years) and American Joint Committee on
      Cancer/TNM stage (pT1N0/x , pT2N0/x , pT3N0/x , pT4N0/x , pTany pN1-3) as
      stratifying variables. The 5-year cancer-specific mortality, other-cause and
      bladder cancer mortality rates were generated through competing-risks Poisson
      regression methodologies. Multivariable competing-risks regression models were
      used to test the effect of age and stage on three different end-points: cancer
      specific mortality, other-cause and bladder cancer mortality. RESULTS: Overall,
      1797 (18.1%), 891 (9.1%) and 3090 (31.2%) patients died of cancer-specific
      mortality, other-cause and bladder cancer mortality, respectively. Following
      stratification according to age and stage, the proportion of patients who
      succumbed to cancer-specific mortality (11.7-21.9%) and other-cause mortality
      (8.9-30.4%) increased with age. In contrast, with increasing stage, the
      proportion of patients who died of cancer-specific mortality increased (7.2
      37.5%), whereas the proportion of other-cause mortality remained stable (18.9
      22.0%). The rate of bladder cancer mortality increased with advancing stage. At
      multivariable competing-risk regression model, besides age and stage, women, type
      of surgery, grade and location were associated with higher cancer-specific
      mortality. Furthermore, ureteral location, stage and grade were associated with
      bladder cancer mortality. CONCLUSIONS: The developed graphical aid for prediction
      of cancer-specific mortality, other-cause, and bladder cancer mortality according
      to age and stage in patients with upper-tract urothelial carcinoma undergoing
      radical nephroureterectomy can be useful for physicians and patients during
      clinical counseling.

PMID- 24033810
TI  - Evaluation of butyrate-induced production of a mannose-6-phosphorylated
      therapeutic enzyme using parallel bioreactors.
AB  - Bioreactor process changes can have a profound effect on the yield and quality of
      biotechnology products. Mannose-6-phosphate (M6P) glycan content and the
      enzymatic catalytic kinetic parameters are critical quality attributes (CQAs) of
      many therapeutic enzymes used to treat lysosomal storage diseases (LSDs). Here,
      we have evaluated the effect of adding butyrate to bioreactor production cultures
      of human recombinant beta-glucuronidase produced from CHO-K1 cells, with an
      emphasis on CQAs. The beta-glucuronidase produced in parallel bioreactors was
      quantified by capillary electrophoresis, the catalytic kinetic parameters were
      measured using steady-state analysis, and mannose-6-phosphorylation status was
      assessed using an M6P-specific single-chain antibody fragment. Using this
      approach, we found that butyrate treatment increased beta-glucuronidase
      production up to approximately threefold without significantly affecting the
      catalytic properties of the enzyme. However, M6P content in beta-glucuronidase
      was inversely correlated with the increased enzyme production induced by butyrate
      treatment. This assessment demonstrated that although butyrate dramatically
      increased beta-glucuronidase production in bioreactors, it adversely impacted the
      mannose-6-phosphorylation of this LSD therapeutic enzyme. This strategy may have
      utility in evaluating manufacturing process changes to improve therapeutic enzyme
      yields and CQAs. 

PMID- 24033811
TI  - Repeated diagnoses of lifetime alcohol use disorders in a prospective study:
      insights into the extent and nature of the reliability and validity problem.
AB  - BACKGROUND: Prior research indicates that assessments of lifetime alcohol use
      disorders (AUDs) show low sensitivity and are unreliable when assessed by a
      single, retrospective interview. This study sought to replicate and extend
      previous research by calculating the lifetime prevalence rate of AUDs using both
      single retrospective assessments of lifetime diagnosis and repeated assessments
      of both lifetime and past-year diagnoses over a 16-year period within the same
      high-risk sample. In addition, this study examined factors that contributed to
      the consistency in reporting lifetime AUDs over time. METHODS: Using prospective
      data, the reliability and validity of lifetime estimates of alcohol dependence
      and AUD were examined in several ways. Data were drawn from a cohort of young
      adults at high and low risk for alcoholism, originally ascertained as first-time
      college freshmen (N = 489 at baseline) at a large, public university and assessed
      over 16 years. RESULTS: Compared with using a single, lifetime retrospective
      assessment of DSM-III disorders assessed at approximately age 34, lifetime
      estimates derived from using multiple, prospective assessments of both past-year
      and lifetime AUD were substantially higher (25% single lifetime vs. 41%
      cumulative past-year vs. 46% cumulative lifetime). This pattern of findings was
      also found when conducting these comparisons at the symptom level. Further, these
      results suggest that some factors (e.g., symptoms endorsed, prior consistency in
      reporting of a lifetime AUD, and family history status) are associated with the
      consistency in reporting lifetime AUDs over time. CONCLUSIONS: Based on these
      findings, lifetime diagnoses using a single measurement occasion should be
      interpreted with considerable caution given they appear to produce potentially
      large prevalence underestimates. These results provide further insight into the
      extent and nature of the reliability and validity problem with lifetime AUDs.

PMID- 24033813
TI  - Factors that predict mortality in children with Wilson disease associated acute
      liver failure and comparison of Wilson disease specific prognostic indices.
AB  - BACKGROUND AND AIMS: Wilson disease (WD) associated acute liver failure (ALF)
      affects children more than adults. The predictors of mortality and outcome in
      patients without encephalopathy are not clear. We investigated the ability of
      prognostic factors and various models including model for end-stage liver disease
      (MELD) to predict mortality among children with WD and ALF. METHODS: We analyzed
      the admission characteristics in 61 children <18 years with WD and ALF. Factors
      associated with mortality on univariate Cox regression analysis were analyzed by
      forward stepwise Cox hazards regression. The prognostic models such as Nazer's
      model, revised Kings College Model, and pediatric end-stage liver disease/model
      for end-stage liver disease (PELD/MELD) score were compared. RESULTS: Of the 145
      children < 18 years with WD, 61 experienced ALF of whom 33 (54%) died, including
      22/27 (81.5%) with encephalopathy and 11/34 (32.4%) without encephalopathy. The
      mean age of children with ALF was 9.7 years, 38(62.3%) were boys. Prognostic
      factors significant for mortality included encephalopathy, international
      normalized ratio, total proteins, total and direct bilirubin, alkaline
      phosphatase, serum creatinine, and white blood cell count. Forward stepwise Cox
      proportional hazards regression identified encephalopathy (hazard ratio 2.88; CI
      1.1-7.4) and total bilirubin (hazard ratio 1.05; CI: 1.02-1.09) as predictors of
      outcome. The area under the receiver operating curve (AUC) of the Nazer index,
      revised King's College Criteria, and PELD/MELD were 0.74, 0.76, and 0.75,
      respectively. CONCLUSIONS: Mortality in children with WD and ALF is 54% including
      81.5% with encephalopathy and 32.4% without encephalopathy. The prognostic
      models, MELD/PELD score, Nazer index and Kings College Criteria are comparable
      with a AUC between 0.74-0.76.

PMID- 24033812
TI  - Immunological and microbiological findings after the application of two
      periodontal surgical techniques: a randomized, controlled clinical trial.
AB  - AIM: To examine microbiological and immunological alterations following two
      periodontal surgical techniques, over a 6-month period. MATERIALS AND METHODS: A
      total of 30 chronic periodontitis patients participated in the present randomized
      controlled clinical trial and were randomized in two groups. Modified Widman flap
      (MWF) was applied in the control group and apically positioned flap (APF),
      without intervention to the bone, in the experimental group. Gingival crevicular
      fluid samples and subgingival plaque samples from the operated sites were
      collected at baseline, 6th, 12th and 24th post-operative week. RESULTS: No major
      differences were noticed in immunological and microbiological profile of patients
      receiving either modified MWF or APF, for a period of 6 months. CONCLUSIONS: The
      choice of the periodontal surgical procedure does not seem to affect the
      immunological and the microbiological profile of patients with chronic
      periodontitis.

PMID- 24033814
TI  - Magnetic resonance imaging of primary and concomitant flexor enthesopathy in the
      canine elbow.
AB  - Flexor enthesopathy is a recently recognized elbow disorder in dogs and
      considered to be an important differential diagnosis for elbow lameness. Primary
      and concomitant forms of the disease have been previously described and
      treatments differ for the two forms. The goal of this prospective study was to
      compare magnetic resonance imaging (MRI) findings for dogs with primary flexor
      enthesopathy (n = 17), concomitant flexor enthesopathy (n = 23), elbow dysplasia
      alone (n = 13), and normal elbows (n = 7). Each elbow joint underwent MRI using
      the same low-field scanner. Sequences included transverse and sagittal T1
      weighted (before and after IV contrast), transverse and sagittal T2-weighted, and
      dorsal STIR. For each elbow, MRI lesions were recorded based on a consensus of
      two observers unaware of group status. Magnetic resonance imaging lesions
      involving flexor tendons were found in 100% of clinically affected joints with
      primary flexor enthesopathy and 96% of clinically affected joints with
      concomitant flexor enthesopathy. Thickened flexor muscles were the most common
      lesions, followed by hyperintense tendon signal and contrast enhancement.
      Irregular, thickened medial humeral epicondyle, edema, and calcified body lesions
      were less frequently observed. Magnetic resonance imaging characteristics of
      flexor enthesopathy were not found in normal joints or those affected by elbow
      dysplasia alone. No significant differences in frequencies and details of
      individual MRI characteristics were found between primary and concomitant flexor
      enthesopathy groups. Findings indicated that MRI is a sensitive technique for
      detection of flexor enthesopathy lesions in dogs, however, MRI characteristics do
      not allow differentiation of primary versus concomitant forms of the disease.

PMID- 24033815
TI  - Acquired factor X deficiency in systemic amyloidosis: management of two cases.

PMID- 24033816
TI  - Renal impairment during the treatment of telaprevir with peginterferon and
      ribavirin in patients with chronic hepatitis C.
AB  - AIM: Renal damage has been reported as an important complication during
      combination treatment of peginterferon (PEG IFN), ribavirin (RBV) and telaprevir
      (TVR) for chronic hepatitis C. However, very little is known about this
      complication. We investigated the role TVR plays in renal damage during this
      triple therapy. METHODS: Twenty-five chronic hepatitis C patients with genotype 1
      and high viral load received TVR in combination with PEG IFN and RBV for 12 weeks
      followed by treatment with PEG IFN and RBV. Renal function of these patients was
      prospectively evaluated for 16 weeks. RESULTS: Creatinine clearance decreased
      significantly during PEG IFN/RBV/TVR treatment. Consequently, serum creatinine
      and cystatin C significantly rose during PEG IFN/RBV/TVR treatment. Serum
      creatinine returned to pretreatment levels after the termination of TVR. The
      increase of serum creatinine and cystatin C from baseline significantly
      correlated with serum TVR level at day 7, which was determined by starting dose
      of TVR per bodyweight . When the patients were classified according to the
      starting dose of TVR per bodyweight, renal impairment was observed only in the
      high-dose (TVR >=33 mg/kg per day) group, not in the low-dose (TVR <33 mg/kg per
      day) group. CONCLUSION: These results suggest that TVR dose per bodyweight is
      important for the occurrence of renal impairment in PEG IFN/RBV/TVR treatment.

PMID- 24033817
TI  - Analysis of factors affecting the life quality of the patients with late stomach
      cancer.
AB  - AIMS AND OBJECTIVES: To provide a theoretical basis for the clinical care of
      patients with late stomach cancer, we investigated the life quality and analysed
      its related factor in the patients with late stomach cancer. BACKGROUND: Due to
      the lack of effective screening methods, stomach cancer usually has been in the
      advanced stage when patients are diagnosed. However, the treatment for late
      stomach cancer is a tough problem in today's medicine. Chemotherapy or
      radiotherapy brings patients physiological and psychological distress and heavy
      financial burden, affecting patients' therapeutic effects, prognosis and life
      quality. DESIGN: The patients with late stomach cancer were included, and then,
      questionnaires about the life quality were completed. METHODS: Questionnaires
      including European Organisation for Research on Treatment of Cancer Quality of
      Life Questionnaire-Core 30, Social Support Rating Scale, Medical Coping Modes
      Questionnaire and Self-rating Anxiety Scale were completed by 173 patients with
      late stomach cancer who received treatment in our hospital between May 2010 and
      May 2011. Correlation analyses were performed. RESULTS: The overall score of the
      life quality of the patients with late stomach cancer was only 29.54 +/- 12.21.
      The social support, medical coping modes, anxiety and patients' clinical data
      (except radiotherapy) markedly affected the overall life quality of the patients
      with late stomach cancer (p < 0.05). CONCLUSION: The life quality of the patients
      with late stomach cancer is poor and is associated with many factors. RELEVANCE
      TO CLINICAL PRACTICE: This study provides a theoretical basis for better nursing
      the patients with late stomach cancer and improving their life quality.

PMID- 24033818
TI  - Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated
      with hand, foot and mouth disease in Spain.
AB  - Hand, foot and mouth disease (HFMD) is a childhood illness frequently caused by
      genotypes belonging to the enterovirus A species, including coxsackievirus (CV)
      A16 and enterovirus (EV)-71. Between 2010 and 2012, several outbreaks and
      sporadic cases of HFMD occurred in different regions of Spain. The objective of
      the present study was to describe the enterovirus epidemiology associated with
      HFMD in the country. A total of 80 patients with HFMD or atypical rash were
      included. Detection and typing of the enteroviruses were performed directly in
      clinical samples using molecular methods. Enteroviruses were detected in 53 of
      the patients (66%). CV-A6 was the most frequent genotype, followed by CV-A16 and
      EV-71, but other minority types were also identified. Interestingly, during
      almost all of 2010, CV-A16 was the only causative agent of HFMD but by the end of
      the year and during 2011, CV-A6 became predominant, while CV-A16 was not
      detected. In 2012, however, both CV-A6 and CV-A16 circulated. EV-71 was
      associated with HFMD symptoms only in three cases during 2012. All Spanish CV-A6
      sequences segregated into one major genetic cluster together with other European
      and Asian strains isolated between 2008 and 2011, most forming a particular
      clade. Spanish EV-71 strains belonged to subgenogroup C2, as did most of the
      European sequences circulated. In conclusion, the recent increase of HFMD cases
      in Spain and other European countries has been due to a larger incidence of
      circulating species A enteroviruses, mainly CV-A6 and CV-A16, and the emergence
      of new genetic variants of these viruses. 

PMID- 24033821
TI  - Two nursing mothers treated with zonisamide: Should breast-feeding be avoided?
AB  - Zonisamide, an antiepileptic drug, is excreted into breast milk, but information
      regarding the safety of breast-feeding while using this drug is limited. We
      present the cases of two nursing mothers, taking 300 and 100 mg/day zonisamide.
      At 5 days after delivery, the milk concentrations and relative infant doses of
      the drug were 18.0 and 5.1 MUg/mL, and 44 and 36%, respectively. In the first
      case, the mother fed colostrum and continued partial breast-feeding thus reducing
      the relative infant dose to 8%. The neonatal serum concentration of zonisamide
      declined to below the limit of detection at day 34 after birth. In the second
      case, the mother breast-fed partially until 2 weeks postpartum. No adverse effect
      was observed in the infants. These findings suggest that mothers taking
      zonisamide should not breast-feed exclusively, but may not have to avoid partial
      breast-feeding, with significant caution regarding adverse effects in infants.

PMID- 24033822
TI  - Reduction in facial hyperpigmentation after treatment with a combination of
      topical niacinamide and tranexamic acid: a randomized, double-blind, vehicle
      controlled trial.
AB  - BACKGROUND: Facial hyperpigmentation occurs in multiple conditions. In addition,
      many Asian women desire a lighter skin color. Thus, there is a need for the
      development of skin lightening agents, and niacinamide and tranexamic acid (TXA)
      are promising candidates. OBJECTIVE: To assess the effectiveness of a combination
      of niacinamide and TXA as a topical moisturizing formulation for treatment of
      irregular facial pigmentation. MATERIALS AND METHODS: A total of 42 Korean women
      (age range: 30-60 years) who were not pregnant, nursing, or undergoing any
      concurrent therapy were enrolled in this study for 8 weeks. Subjects used a twice
      daily regimen of either a moisturizing cream containing 2% niacinamide + 2% TXA
      (test formulation; n = 21) or cream vehicles (vehicle control; n = 21) in
      addition to an assigned sunscreen each morning. Pigmentation was measured
      objectively using a mexameter and chromameter, in addition to physicians'
      assessment using clinical photographs. RESULTS: The niacinamide + TXA formulation
      regimen was significantly (P < 0.05) more effective than the vehicle control
      formulation regimen in reducing the appearance of pigmentation. CONCLUSION: A
      formulation containing the combination of niacinamide + TXA reduced the
      appearance of irregular pigmentation, providing an effect beyond that achieved
      with sunscreen.

PMID- 24033819
TI  - The effectiveness of propranolol in treating infantile haemangiomas: a meta
      analysis including 35 studies.
AB  - AIMS: Propranolol may have shown excellent results as a first line therapy in
      infantile haemangiomas (IHs) at all sites in the body, but this conclusion
      remains controversial. In an attempt to resolve this issue, we performed a meta
      analysis. METHODS: A search of the literature using PubMed, MEDLINE, Cochrane
      Library databases and China National Knowledge Infrastructure (CNKI) was
      performed to identify studies which estimated the efficacy of propranolol therapy
      in infants with haemangiomas all sites of the body. The pooled odds ratio (OR)
      along with the corresponding 95% confidence intervals (CI) were assessed using a
      fixed effects model. RESULTS: Thirty-five studies involving 324 infantile
      haemangioma(IH) patients and 248 controls were retrieved and analyzed. The
      efficacy of propranolol was greater than other therapies in treating IHs (OR =
      9.67, 95% CI 6.62, 14.12, P < 0.001). In a stratified analysis by sites of
      tumour, propranolol was a more effective therapy when compared with steroids (OR
      = 9.67, 95% CI 6.61, 14.15, P < 0.001), vincristine (OR = 9.00, 95% CI 2.15,
      37.66, P = 0.003) and laser treatment (OR = 9.00, 95% CI 1.42, 57.12, P = 0.020)
      in treating cutaneous IHs (OR = 24.95, 95% CI 9.48, 65.64, P < 0.001), peri
      ocular IHs (OR = 9.39, 95% CI 3.88, 22.71, P < 0.001), infantile airway
      haemangiomas (OR = 20.91, 95% CI 7.81, 55.96, P < 0.001) and infantile hepatic
      haemangiomas (OR = 9.89, 95% CI 1.20, 81.54, P = 0.033). CONCLUSION: The current
      meta-analysis provided strong evidence for propranolol as a first line therapy
      for IHs.

PMID- 24033824
TI  - What is your diagnosis? An endotracheal wash from a dyspneic 3-month-old female
      Labrador Retriever.

PMID- 24033823
TI  - Vernalization requirement duration in winter wheat is controlled by TaVRN-A1 at
      the protein level.
AB  - Winter wheat requires a period of low temperatures to accelerate flowering
      (vernalization). This requirement could make winter wheat more vulnerable to
      elevated global temperature via insufficient vernalization. All known
      vernalization genes are cloned according to qualitative variation in
      vernalization requirement between spring and winter wheat, but the genes
      controlling quantitative variation for more or less vernalization requirement
      among winter wheat cultivars remain unknown. We report here that the gene for the
      vernalization requirement duration in winter wheat was cloned using a BC(1)F(2:3)
      population that segregated in a 3:1 ratio of early-flowering plants and late
      flowering plants after vernalization for 3 weeks. The positional cloning of the
      gene for vernalization requirement duration demonstrated that this trait is
      controlled by TaVRN-A1 at the protein level. The Ala(180) in vrn-A1a, encoded by
      the dominant allele for 3-week vernalization, was mutated to Val(180) in vrn-A1b,
      encoded by the recessive allele for 6-week vernalization. Further studies with in
      vitro protein pull-down assays and immunoprecipitation analyses indicated that
      the mutated Val(180) in vrn-A1b protein decreased the ability to bind with TaHOX1
      (the first homeobox protein in Triticum aestivum). The direct binding of TaVRN-A1
      and TaHOX1 proteins was confirmed in the nucleus of living plant cells by
      bimolecular fluorescence complementation (BiFC) analyses. The TaHOX1 gene was
      found to be upregulated by low temperatures, and to have a significant genetic
      effect on heading date, suggesting that TaHOX1 functions in the flowering pathway
      in winter wheat.

PMID- 24033825
TI  - Social research and biodiversity conservation.

PMID- 24033826
TI  - The (mis)management of migrant nurses in the UK: a sociological study.
AB  - AIM: To examine Nepali migrant nurses' professional life in the UK. BACKGROUND:
      In the late 1990 s the UK experienced an acute nursing shortage. Within a decade
      over 1000 Nepali nurses migrated to the UK. METHOD: A multi-sited ethnographic
      approach was chosen for this study. Between 2006 and 2009, 21 in-depth interviews
      with Nepali nurses were conducted in the UK using snowballing sampling. RESULT:
      Nepali migrant nurses are highly qualified and experienced in specialised areas
      such as critical care, management and education. However, these nurses end up
      working in the long-term care sector, providing personal care for elderly people 
      an area commonly described by migrant nurses as British Bottom Care (BBC). This
      means that migrant nurses lack career choices and professional development
      opportunities, causing them frustration and lack of job satisfaction. CONCLUSION:
      International nurse migration is an inevitable part of globalisation in health.
      Nurse managers and policy makers need to explore ways to make better use of the
      talents of the migrant workforce. IMPLICATIONS FOR NURSING MANAGEMENT: We offer a
      management strategy to bring policies for the migrant workforce into line with
      the wider workforce plans by supporting nurses in finding jobs relevant to their
      expertise and providing career pathways.

PMID- 24033827
TI  - Does the severity of hangovers decline with age? Survey of the incidence of
      hangover in different age groups.
AB  - BACKGROUND: Alcohol hangover is a growing research area, but differences across
      the life span have not been assessed. Here, we test the hypothesis that the
      severity of hangovers depends on age. METHODS: A cross-sectional study of 51,645
      men and women aged 18 to 94 years old, who participated in the population-based
      Danish Health Examination Study (DANHES) in Denmark between 2007 and 2008, formed
      the database for our study. RESULTS: The incidence of severe hangover was lower
      among older than younger participants. Odds ratios for experiencing severe
      hangover following an episode of binge drinking were 6.8, 4.8, 3.0, and 2.0 among
      the 18 to 29, 30 to 39, 40 to 49, and 50 to 59-year-old men, compared with those
      aged 60+ years. For women, similar results were obtained. This finding could not
      be explained by the usual amount of alcohol consumption, frequency of binge
      drinking, or the proportion of alcohol consumed with meals. CONCLUSIONS: We found
      that hangover following engagement in binge drinking is much more common in the
      young than in the older age groups.

PMID- 24033828
TI  - Interaction between caspofungin or voriconazole and cefoperazone-sulbactam or
      piperacillin-tazobactam by in vitro and in vivo methods.
AB  - Immunosuppressive patients are at risk of fungal and bacterial infections.
      Therefore, these patients receive prophylactic, preemptive, empirical or target
      antifungal and concomitant antibiotic therapy. To this end, caspofungin (CAS) or
      voriconazole (VRC) antifungals and cefoperazone-sulbactam (CPZ/SAM) or
      piperacillin-tazobactam (PIP/TAZ) antibiotics may be used. Here, we aimed to
      investigate the interaction between these antifungals and antibiotics by in vitro
      and in vivo methods. The interaction was tested by chequerboard analysis and
      fractional inhibitory concentration index (FICI). It was also tested in a
      neutropenic mice-invasive candidiasis model and evaluated by fungal burden in
      kidney tissue of infected animals from the first day to the fifth day of
      treatment with 24 h intervals. A synergism was detected between CAS and CPZ/SAM
      (FICI = 0.1) and PIP/TAZ (FICI = 0.3). Fungal burden in tissues of drug-treated
      mice was reduced compared with controls in a time-dependent manner. In comparison
      with CAS-alone treated group, there were 1.32 log10 reductions of fungal burden
      in CAS + CPZ/SAM (p = 0.002) and in CAS + PIP/TAZ group (p = 0.14). The same
      interactions were not found with VRC and antibiotics. CPZ/SAM had stronger
      synergistic interaction with CAS than PIP/TAZ. The mechanism of synergism is not
      well understood. This is most likely due to an increase in the anticandidal
      effect of CAS plus antibiotics.

PMID- 24033829
TI  - Minimal influence of expertise on the evaluation of colorectal neoplastic lesions
      by confocal laser endomicroscopy.
AB  - BACKGROUND AND AIMS: Three different confocal laser endomicroscopy (CLE)
      diagnostic systems including Maiz, Sanduleanu, and Qilu had been developed to
      differentiate between benign and neoplastic colorectal lesions. This study was
      designed to compare and evaluate these three diagnostic systems by different
      levels of expertise. METHODS: Thirty-nine patients with 50 colorectal polyps,
      including 23 hyperplastic polyps and 27 adenomas diagnosed by histopathology,
      were recruited. Four confocal images (two superficial images and two deeper
      images) and one conventional white-light endoscopic image were selected from each
      of the 50 lesions in this study by an experienced endomicroscopist. Selected
      images were evaluated by three experienced CLE investigators and three non
      experienced ones. The accuracy and interobserver agreement between experienced
      and non-experienced investigators for prediction of colorectal neoplasia were
      determined. RESULTS: The diagnostic accuracy was 84%, 81%, and 87%, respectively,
      using the Maiz, Sanduleanu, and Qilu diagnostic system, while the sensitivity was
      85%, 79%, and 85%, the specificity was 83%, 84%, and 89%, respectively. There is
      no significant difference on diagnostic accuracy between experienced and non
      experienced investigators. In addition, there is a short learning curve for non
      experienced CLE investigators identified in this study. CONCLUSIONS: The three
      diagnostic systems for the prediction of colorectal hyperplastic polyp or adenoma
      have a high accuracy, sensitivity, and specificity. The diagnostic accuracy was
      not significantly influenced by the expertise in CLE.

PMID- 24033830
TI  - Assessment of adequate safety margin using single coupling interval-upper limit
      of vulnerability test.
AB  - PURPOSE: Upper limit of vulnerability (ULV) testing using T-wave scanning shocks
      at multiple coupling intervals correlates well with defibrillation threshold
      (DFT), but remains underutilized in clinical practice. We measured DFT and ULV at
      a single coupling interval (SCI), with the aim to identify adequate safety margin
      at a coupling interval that correlates best with DFT. METHODS: Consecutive
      patients undergoing implantable cardioverter defibrillator implantation underwent
      simultaneous SCI-ULV and DFT assessment. Following a drive train of 400 ms, a T
      wave-coupled shock was delivered. To minimize shocks, patients were randomized to
      programmed shock at 20 ms before peak (Group I), at peak (Group II), or 20 ms
      after peak (Group III) of T wave. An initial T-wave test shock at 9 J was
      followed by +/-2 J shocks, until SCI-ULV was ascertained. Device rescue shocks
      were programmed at test shock +2 J and +4 J shocks followed by external rescue
      shock. RESULTS: There were 200 patients: 66 patients in Group I, 67 patients each
      in Groups II and III; mean age was 68.9 +/- 12.4 years; 75% of patients men, 66%
      with ischemic heart disease and mean ejection fraction of 27.1 +/- 7.1%. Overall,
      the mean number of ventricular fibrillation induction was 1.39 +/- 0.8, mean SCI
      ULV energy was 7.97 +/- 3.39 J, and mean DFT was 8.68 +/- 3.19 J. The correlation
      between SCI-ULV and DFT improved from Group I to Group III and was best in Group
      III (r(2) = 0.689). There were no major adverse events. CONCLUSIONS: SCI-ULV
      measured 20 ms after the peak of the T wave correlates well with DFT for
      assessment of adequate safety margin.

PMID- 24033831
TI  - Functional and transcriptomic analysis of the regulation of osteoblasts by
      mechano-growth factor E peptide.
AB  - Mechano-growth factor (MGF), a splice variant of insulin-like growth factor I
      (IGF-I), was discovered by Goldspink and colleagues in 1996; since then many
      studies have implicated MGF as an important local tissue repair factor. Although
      the short 24-amino-acid C-terminal peptide of MGF (MGF-Ct24E) has a variety of
      biological activities, its role in bone formation has not yet been clarified.
      Accordingly, the aim of this study was to investigate the role of MGF-Ct24E in
      the proliferation, differentiation, and mineralization of rat calvarial
      osteoblasts. Interestingly, although MGF-Ct24E significantly increased the
      proliferation and retarded the differentiation of osteoblasts during the first 3
      days, prolonged treatment with MGF-Ct24E for up to 3 weeks promoted cell
      differentiation. To determine the molecular mechanisms behind this plurality, we
      carried out global transcriptional profiling of osteoblasts in response to MGF
      Ct24E and identified differentially expressed genes by bioinformatics analysis.
      Gene ontology analysis indicated that MGF-Ct24E enhanced the expression of genes
      associated with osteoblast proliferation and the cell cycle and downregulated
      genes involved with osteoblast differentiation, skeletal system, and bone
      development. Moreover, KEGG pathway-based analysis indicated that MGF-Ct24E
      directly altered focal adhesion and cell cycle progression, in addition to
      regulating the actin cytoskeleton and gap junctions. In conclusion, MGF-Ct24E has
      a marked ability to increase bone formation by increasing cell proliferation and
      delaying cell differentiation during prophase, as well as by stimulating
      osteoblast differentiation during the advanced stage. The mechanism of action of
      MGF-Ct24E during the initial stages of bone formation in vitro involves
      upregulation of the expression of genes involved in proliferation and cell cycle
      progression, and the repression of differentiation-related genes. 

PMID- 24033832
TI  - A two-yr prospective study of bone health in children after renal transplantation
      employing two imaging techniques.
AB  - The aim of this study was to prospectively and longitudinally evaluate bone
      properties with the use of two bone imaging techniques (dual energy X-ray
      absorptiometry [DXA], and quantitative ultraSonography [QUS]) in pediatric renal
      transplant recipients. Fourteen patients (eight boys and six girls) with a mean
      age of 12.25 +/- 3.11 yr (range: 8-17.5 yr) completed a two-yr follow-up.
      Measurements of bone mineral density (BMD) by DXA at lumbar spine and hip and
      speed of sound (SOS) by QUS at radius and tibia were performed at the beginning
      and at the end of the study. A significant improvement in mean Z-score of SOS
      values measured at tibia (1.01 +/- 1.31 vs. -0.46 +/- 1.14, p = 0.005) was
      observed. On the contrary, mean Z-score of BMD values measured at femoral neck
      was significantly reduced (-1.95 +/- 2.15 vs. -0.33 +/- 1.13, p = 0.041).
      Finally, multivariate stepwise regression analyses showed that glomerular
      filtration rate at the beginning of the study was the best predictor of the
      difference in BMD Z-scores measured at lumbar spine. Additionally, values of
      intact parathormone (iPTH) at the beginning of the study and the change in iPTH
      throughout the study predicted the 72.3% of the difference in Z-score of SOS
      measured at radius with an inverse relationship.

PMID- 24033833
TI  - Influence of splenectomy in patients with liver cirrhosis and hypersplenism.
AB  - AIM: Splenectomy improves hypersplenic thrombocytopenia in cirrhotic patients
      with hypersplenism. However, the long-term influence of splenectomy has not been
      clarified. We examined whether splenectomy improved liver fibrosis and caused
      immunological changes. METHODS: We collected liver and spleen specimens and
      peripheral blood (PB) from 26 patients with hepatitis C virus-related liver
      cirrhosis. An immunohistochemical examination of CD4, CD8, forkhead box P3,
      granzyme B and transforming growth factor-beta1, and Masson-trichrome stain were
      performed in spleen and liver tissues and in seven cases of follow-up liver
      biopsy sections obtained after splenectomy. We obtained PB before and at various
      intervals after splenectomy. We also examined the ratio of CD4(+) and CD8(+)
      lymphocytes in PB using flow cytometry. RESULTS: We observed improvements in
      liver fibrosis in four biopsy specimens obtained after splenectomy, in which
      fibrotic areas significantly decreased from 19.5% to 8.2% (P < 0.05). Increases
      were also observed in the ratio of CD8(+) cells in PB after splenectomy, which
      resulted in a significant decrease in the CD4(+) /CD8(+) ratio (P < 0.001). The
      carcinogenic rate in patients with a CD4(+)  : CD8(+) ratio that decreased by
      more than 0.5 at 1 month after splenectomy was significantly lower than that in
      patients with a ratio that decreased by less than 0.5 (P < 0.05). CONCLUSION:
      Splenectomy may improve liver fibrosis and cause beneficial immunological changes
      in cirrhotic patients with hepatitis. Improvements in antitumor mechanisms can be
      also expected.

PMID- 24033834
TI  - Ghrelin prevents the development of dermal fibrosis in bleomycin-induced
      scleroderma.
AB  - BACKGROUND: Scleroderma is a chronic inflammatory disease characterized by
      widespread fibrosis of the skin and the internal organs. Ghrelin is a polypeptide
      hormone produced by various tissues and inflammatory cells. In experimental
      studies, ghrelin has been shown to have anti-inflammatory and antioxidant
      effects, in addition to its metabolic actions. AIM: To evaluate the potential
      preventive effects of ghrelin on a mouse model of bleomycin (BLM)-induced
      scleroderma. METHODS: This study involved five groups of BALB/c mice (n = 7 in
      each group). Mice in the control group received 100 MUL/day of phosphate-buffered
      saline (PBS) subcutaneously, while the other four groups were given 100 MUg/day
      of BLM (dissolved in 100 MUL PBS) subcutaneously. Three of the BLM-treated groups
      received intraperitoneal doses (10 ng/kg/day) of acylated, nonacylated or total
      ghrelin. Animals were killed at the end of the fourth week, and blood and tissue
      samples were collected for further analysis. Dermal thickness, serum levels of
      transforming growth factor-beta1, numbers of inflammatory cells on the dermal
      layer and numbers of alpha-smooth muscle actin-positive cells were determined.
      RESULTS: BLM increased dermal thickness, numbers of inflammatory cells on the
      dermal layer and activity of the myofibroblastic cells. Application of acylated,
      nonacylated and total ghrelin decreased the infiltration of inflammatory cells
      and the activity of the myofibroblastic cells, and reduced dermal fibrosis.
      CONCLUSIONS: Based on these results, it appears that ghrelin has an antifibrotic
      action, in addition to the anti-inflammatory and antioxidant effects that have
      been documented previously. The pathogenic and therapeutic roles of ghrelin in
      scleroderma should be evaluated by further studies.

PMID- 24033835
TI  - Epithelioid sarcoma-like (pseudomyogenic) hemangioendothelioma, clinically
      mimicking dermatofibroma, diagnosed by skin biopsy in a 30-year-old man.
AB  - Epithelioid sarcoma-like (pseudomyogenic) hemangioendothelioma (ESHE) represents
      a rare soft tissue and bone tumor that typically presents as nodule(s) in the
      distal extremities of young adults. The nodules traverse several tissue planes
      simultaneously and can involve the dermis, subcutis, skeletal muscle and bone.
      ESHE shares clinical and microscopic features with epithelioid sarcoma (ES), and,
      accordingly, is commonly misdiagnosed as ES. However, unlike ES, which has a poor
      prognosis, ESHE commonly follows an indolent course. Herein, we report a case of
      ESHE diagnosed by skin biopsy that clinically mimicked a dermatofibroma. We also
      provide clinical photographs of the lesions in various stages of development,
      representing information that has not been previously published, to our
      knowledge. 

PMID- 24033836
TI  - Psychosocial effects of Tai Chi exercise on people with rheumatoid arthritis.
AB  - AIMS AND OBJECTIVES: To investigate the perceived psychosocial effects of
      participating in taught sessions of Tai Chi on people diagnosed with rheumatoid
      arthritis (RA). BACKGROUND: Tai Chi is thought to be psychologically as well as
      physically beneficial for people with arthritis. DESIGN: This study adopted a
      qualitative approach to follow-up participants who had previously demonstrated
      physical and psychological benefits from a specifically modified Tai Chi
      programme in an attempt to explore perceived psychosocial improvements. METHODS:
      Nineteen semi-structured, audio-taped, interviews were carried out with
      participants who had taken part in, twice weekly, group-based Tai Chi sessions
      for 12 weeks. Data from transcripts were analysed using thematic analysis.
      RESULTS: Analysis suggests that participating in shared Tai Chi sessions provides
      increased awareness of the links between mind and body; reduces anxiety and
      depression; and improves self-esteem, self-efficacy and motivation. It was
      particularly striking to find that the highly structured nature of Tai Chi was
      felt to improve memory and seemed to offer aesthetic experiences through
      developing graceful, 'fluid' moves rather than the 'jarring' movements often
      imposed by having RA. Such group sessions were found to provide social support
      and help improve participants' sense of perspective. CONCLUSION: Although small
      scale, this study suggests that Tai Chi has the potential to offer psychosocial
      benefits for people with RA. RELEVANCE TO CLINICAL PRACTICE: Offering Tai Chi
      alongside traditional treatments for RA could promote psychological health and
      well-being, help inform clinical decision-making and prove cost-effective.

PMID- 24033837
TI  - Computed tomography of canine elbow joints affected by primary and concomitant
      flexor enthesopathy.
AB  - Flexor enthesopathy is an important differential diagnosis for elbow lameness in
      dogs. The disorder can be a primary cause of elbow lameness or concomitant with
      other elbow pathology. Since treatment differs for primary and concomitant forms
      of flexor enthesopathy, a noninvasive method for distinguishing between them is
      needed. In the current prospective study, computed tomographic (CT) examination
      was performed before and after IV injection of contrast in 17 dogs with primary
      flexor enthesopathy, 24 dogs with concomitant flexor enthesopathy, 13 dogs with
      elbow dysplasia, and seven normal dogs. Dogs were assigned to groups based on
      results of clinical examination and at least three other imaging modalities.
      Computed tomographic lesions consistent with flexor enthesopathy were found in
      all clinically affected joints with primary flexor enthesopathy and in 29 of the
      30 clinically affected joints with concomitant flexor enthesopathy. Those lesions
      were not found in sound elbows or joints affected by elbow dysplasia. Flexor
      lesions detected in dogs with primary flexor enthesopathy were not significantly
      different from those detected in dogs with the concomitant form. Findings
      indicated that CT can be applied to detect flexor enthesopathy, but a distinction
      between the primary and concomitant forms was not always possible. Authors
      recommend the use of multiple diagnostic techniques for treatment planning in
      affected dogs. 

PMID- 24033838
TI  - Commentary: malignant melanoma in pigmented skin: does the current interventional
      model fit a different clinical, histological, and molecular entity?

PMID- 24033839
TI  - Commentary: Alcohol plus chlorhexidine is more efficient than alcohol alone for
      phenol-based chemical matricectomy: in vitro study.

PMID- 24033840
TI  - Femur fracture in a woman with severe factor X deficiency - an experience using
      factor X concentrate in surgery.

PMID- 24033841
TI  - Swallow syncope after cardiac surgery in a sheep.

PMID- 24033842
TI  - Discrimination between cutaneous pigmentation and erythema: comparison of the
      skin colorimeters Dermacatch and Mexameter.
AB  - BACKGROUND/PURPOSE: Reproducibility and specificity of the present skin
      colorimeters is still limited as alterations in erythema can bias the measurement
      of melanin and vice versa. Here, Dermacatch((r)) , a new colorimeter covering the
      visible light spectrum, has been compared with Mexameter((r)) , an established
      narrow-band reflectance spectrophotometer. METHODS: Repeated measurements with
      both devices were initially collected on colour charts. Then, measures were
      compared on 12 human volunteers before and after exposure to UVB, and/or
      modulation of skin erythema. RESULTS: In vitro sensitivity of Dermacatch to
      erythema/melanin covered a broader wavelength spectrum than Mexameter while in
      vivo sensitivity of both devices was similar. Interestingly, Mexameter's melanin
      and erythema values were falsely affected by an increase in erythema or variation
      in pigmentation respectively. On the contrary, Dermacatch's melanin and erythema
      values remained constant in the same circumstances. Furthermore, as Mexameter was
      at least twice less reproducible than Dermacatch, Mexameter showed an increased
      risk of a confusion over the detection of erythema or melanin fluctuations.
      CONCLUSION: The analysis of more than 18,000 measures indicated that, Dermacatch
      has a significantly higher specificity and reproducibility than Mexameter in the
      measurement of skin pigmentation and erythema.

PMID- 24033843
TI  - Outcomes of combination therapy for chronic antibody-mediated rejection in renal
      transplantation.
AB  - AIM: Chronic antibody-mediated rejection (CAMR) in renal transplant patients has
      poor allograft outcomes. However, treatment strategy has not been established
      yet. Herein, we present short-term outcomes of combination therapy for CAMR.
      METHODS: We identified nine patients with CAMR or suspicious CAMR who were
      treated with antihumoral therapy from 2010 to 2011 and analyzed their medical
      records retrospectively. RESULTS: Five patients had CAMR, and four patients had
      suspicious CAMR. Severe transplant glomerulopathy (TG) was observed in seven
      patients. The estimated glomerular filtration rate (eGFR) was decreased in all
      patients before treatment. We used three different treatment regimens: (i) high
      dose intravenous immunoglobulin (IVIG) and rituximab; (ii) high-dose IVIG,
      rituximab, and bortezomib; and (iii) plasmapheresis with low-dose IVIG, rituximab
      and bortezomib. After treatment with one of these three regimens, graft function
      improved or stabilized in six patients, whereas three patients showed further
      deterioration of eGFR. The third regimen suppressed deterioration of renal
      function in all patients. Most patients showed no progression of proteinuria.
      Infectious complications due to Pneumocystis jirovecii pneumonia and herpes
      zoster occurred in two patients. CONCLUSION: Combination therapy for CAMR might
      be effective, even in patients with relatively late-stage CAMR.

PMID- 24033844
TI  - Cysteine sulfinic acid decarboxylase regulation: A role for farnesoid X receptor
      and small heterodimer partner in murine hepatic taurine metabolism.
AB  - AIM: Bile acid synthesis is regulated by nuclear receptors including farnesoid X
      receptor (FXR) and small heterodimer partner (SHP), and by fibroblast growth
      factor 15/19 (FGF15/19). We hypothesized that hepatic cysteine sulfinic acid
      decarboxylase (CSAD) (a key enzyme in taurine synthesis) is regulated by bile
      acids (BA). The aim of this study was to investigate CSAD regulation by BA
      dependent regulatory mechanisms. METHODS: Mice were fed a control diet or a diet
      supplemented with either 0.5% cholate or 2% cholestyramine. To study BA dependent
      pathways, we utilized GW4064 (FXR agonist), FGF19 or T-0901317 (liver X receptor
      [LXR] agonist) and Shp-/- mice. Tissue mRNA was determined by quantitative
      reverse transcription polymerase chain reaction. Amino acids were measured by
      high-performance liquid chromatography. RESULTS: Mice supplemented with dietary
      cholate exhibited reduced hepatic CSAD mRNA while those receiving cholestyramine
      exhibited increased mRNA. Activation of FXR suppressed CSAD mRNA expression
      whereas CSAD expression was increased in Shp-/- mice. Hepatic hypotaurine
      concentration (the product of CSAD) was higher in Shp-/- mice with a
      corresponding increase in serum taurine conjugated BA. FGF19 administration
      suppressed hepatic cholesterol 7-alpha-hydroxylase (CYP7A1) mRNA but did not
      change CSAD mRNA expression. LXR activation induced CYP7A1 mRNA yet failed to
      induce CSAD mRNA expression. CONCLUSION: BA regulate CSAD mRNA expression in a
      feedback fashion via mechanisms involving SHP and FXR but not FGF15/19 or LXR.
      These findings implicate BA as regulators of CSAD mRNA via mechanisms shared with
      CYP7A1.

PMID- 24033845
TI  - Clinical and cytogenetic results of a large series of amniocentesis cases from
      Turkey: report of 6124 cases.
AB  - AIM: The aim of this study was to document the clinical and cytogenetic results
      of a large series of amniocentesis (AS) cases from Turkey. MATERIAL AND METHODS:
      Second-trimester amniocentesis cases performed in Suleymaniye Maternity Hospital
      for Research and Training between January 2007 and December 2011 were included.
      RESULTS: During this period, 6124 AS were performed. Indications were increased
      risk in maternal serum screening (MSS) (56%), advanced maternal age (29%) and
      pathologic ultrasound finding (11.5%). Most frequent MSS abnormality was abnormal
      triple test result (58%). Overall culture success rate was 98.8%. Chromosomal
      abnormality was detected in 215 (3.6%) of the 6052 cytogenetic results (74.9%
      numerical, 25.1% structural). Most frequent numerical chromosomal abnormality was
      trisomy 21 (61.9%). Clinically insignificant polymorphisms were the most frequent
      structural changes (n = 571). Most frequent polymorphism was increase in
      heterochromatin region in the 1st chromosome (n = 158). Advanced maternal age had
      a positive predictive value of 5.2%. Among the MSS tests, the combined test had
      the highest positive predictive value (5.2%). CONCLUSIONS: In our study, abnormal
      MSS (and among these, abnormal triple test result) was the most frequent
      indication for amniocentesis. Our overall culture success rate was 98.8%.
      Frequency of major chromosomal abnormality was 3.2% and trisomy 21 was the most
      frequent abnormality.

PMID- 24033846
TI  - Genetic dissection of a TIR-NB-LRR locus from the wild North American grapevine
      species Muscadinia rotundifolia identifies paralogous genes conferring resistance
      to major fungal and oomycete pathogens in cultivated grapevine.
AB  - The most economically important diseases of grapevine cultivation worldwide are
      caused by the fungal pathogen powdery mildew (Erysiphe necator syn. Uncinula
      necator) and the oomycete pathogen downy mildew (Plasmopara viticola). Currently,
      grapegrowers rely heavily on the use of agrochemicals to minimize the potentially
      devastating impact of these pathogens on grape yield and quality. The wild North
      American grapevine species Muscadinia rotundifolia was recognized as early as
      1889 to be resistant to both powdery and downy mildew. We have now mapped
      resistance to these two mildew pathogens in M. rotundifolia to a single locus on
      chromosome 12 that contains a family of seven TIR-NB-LRR genes. We further
      demonstrate that two highly homologous (86% amino acid identity) members of this
      gene family confer strong resistance to these unrelated pathogens following
      genetic transformation into susceptible Vitis vinifera winegrape cultivars. These
      two genes, designated resistance to Uncinula necator (MrRUN1) and resistance to
      Plasmopara viticola (MrRPV1) are the first resistance genes to be cloned from a
      grapevine species. Both MrRUN1 and MrRPV1 were found to confer resistance to
      multiple powdery and downy mildew isolates from France, North America and
      Australia; however, a single powdery mildew isolate collected from the south
      eastern region of North America, to which M. rotundifolia is native, was capable
      of breaking MrRUN1-mediated resistance. Comparisons of gene organization and
      coding sequences between M. rotundifolia and the cultivated grapevine V. vinifera
      at the MrRUN1/MrRPV1 locus revealed a high level of synteny, suggesting that the
      TIR-NB-LRR genes at this locus share a common ancestor.

PMID- 24033847
TI  - Exploring the impact of transformational leadership on nurse innovation
      behaviour: a cross-sectional study.
AB  - AIM: This study explored the influences of transformational leadership on nurse
      innovation behaviour and the mediating role of organisational climate.
      BACKGROUND: Recently, global nursing experts have been aggressively encouraging
      nurses to pursue innovation in nursing in order to improve nursing outcomes.
      Nursing innovation, in turn, is affected by nursing leadership. METHOD: We
      employed a questionnaire survey to collect data, and selected a sample of nurses
      from hospitals in Taiwan. A total of 439 valid surveys were obtained.
      Hierarchical multiple regression model analysis was conducted to test the study
      hypothesis. RESULT: The mean values of agreement of nurse innovation behaviour
      and transformational leadership were 3.40 and 3.78, respectively. Patient safety
      climate and innovation climate were found to have full mediating effects on the
      relationship between transformational leadership and innovation behaviour.
      CONCLUSION: Organisational climate has a significant impact on innovation
      behaviour. Transformational leadership has indirect effects on innovation
      behaviour via the mediation of patient safety climate and innovation climate.
      IMPLICATIONS FOR NURSING MANAGEMENT: Hospitals should enhance transformational
      leadership by designing leadership training programmes and establishing
      transformational culture. In addition, nursing managers should foster nursing
      innovation through improvements in organisational climate.

PMID- 24033848
TI  - Using a systematic approach to select flagship species for bird conservation.
AB  - Conservation marketing campaigns that focus on flagship species play a vital role
      in biological diversity conservation because they raise funds and change people's
      behavior. However, most flagship species are selected without considering the
      target audience of the campaign, which can hamper the campaign's effectiveness.
      To address this problem, we used a systematic and stakeholder-driven approach to
      select flagship species for a conservation campaign in the Serra do Urubu in
      northeastern Brazil. We based our techniques on environmental economic and
      marketing methods. We used choice experiments to examine the species attributes
      that drive preference and latent-class models to segment respondents into groups
      by preferences and socioeconomic characteristics. We used respondent preferences
      and information on bird species inhabiting the Serra do Urubu to calculate a
      flagship species suitability score. We also asked respondents to indicate their
      favorite species from a set list to enable comparison between methods. The
      species' traits that drove audience preference were geographic distribution,
      population size, visibility, attractiveness, and survival in captivity. However,
      the importance of these factors differed among groups and groups differed in
      their views on whether species with small populations and the ability to survive
      in captivity should be prioritized. The popularity rankings of species differed
      between approaches, a result that was probably related to the different ways in
      which the 2 methods measured preference. Our new approach is a transparent and
      evidence-based method that can be used to refine the way stakeholders are engaged
      in the design of conservation marketing campaigns.

PMID- 24033849
TI  - What is your diagnosis? Equine transtracheal wash fluid.

PMID- 24033850
TI  - KISS1 expression in colorectal cancer.
AB  - Kisspeptins, the products of the KISS1 gene, are involved in cancer invasion,
      migration, metastasis and angiogenesis, while they induce apoptosis in various
      cancers. Herein, we studied KISS1 expression in colorectal cancer. We analyzed
      KISS1 expression using immunohistochemistry and image analysis in normal and
      malignant tissue samples from 60 patients with colorectal adenocarcinoma. The
      results correlated with various clinicopathological parameters. The expression of
      KISS1 was much higher in normal than in malignant colonic mucosa. However, among
      malignant tissues, KISS1 expression was higher in larger tumors (>4 cm) than in
      smaller ones (<=4 cm) and in stages III and IV than in stages I and II. In
      addition, it was higher in patients with lymph node metastases. Moreover, KISS1
      levels in the normal mucosa and their difference from those in the malignant
      mucosa were higher in the right part of the large intestine than in the left one.
      KISS1 expression is reduced during the malignant transformation of the colonic
      mucosa and there is a difference in the expression pattern between the right and
      the left part of the large intestine. However, larger and advanced colorectal
      tumors express higher KISS1 levels than smaller and localized ones.

PMID- 24033851
TI  - Efficacy of biologics in the treatment of moderate-to-severe plaque psoriasis: a
      systematic review and meta-analysis of randomized controlled trials with
      different time points.
AB  - BACKGROUND: Differences in response rates of biologics for the treatment of
      moderate-to-severe plaque psoriasis have been reported in several meta-analyses
      published to date. However, the usefulness of these meta-analyses is limited as
      they do not reflect currently approved recommendations in the Summaries of
      Product Characteristics (SmPCs) and clinical practice. OBJECTIVE: To estimate the
      efficacy of biologics in the treatment of moderate-to-severe plaque psoriasis in
      the currently approved conditions of use in the European Union (EU) at relevant
      time points for evaluation of response in clinical practice (failure assessment
      as recommended in the SmPCs and/or at the end of the induction phase). METHODS:
      Randomized placebo-controlled studies of biologics currently authorized in the EU
      in adult patients with a diagnosis of moderate-to-severe plaque psoriasis were
      searched in several databases. A meta-analysis using fixed or random-effects
      model depending on heterogeneity across and within studies was performed. The
      efficacy was estimated using risk difference (RD) of Psoriasis Area and Severity
      Index (PASI) 50, PASI 75 and PASI 90 response rates at the endpoint in clinical
      trials, at the end of the induction phase (week 24) and at the time points
      recommended for evaluation of primary failure in the approved SmPCs. Several
      sensitivity analyses were performed to assess for robustness. RESULTS: Sixteen
      publications met the defined inclusion criteria. According to this meta-analysis
      at the primary endpoint times, infliximab (at week 10) has the greatest
      probability of response with respect to placebo for all PASI-based efficacy
      measures (PASI 50, PASI 75 and PASI 90). At the end of the induction phase (week
      24), ustekinumab 45 mg has the greatest probability of achieving PASI 75 response
      (RD 75.5%, 95%CI 71.5-79.4%], followed by ustekinumab 90 mg, infliximab,
      adalimumab and etanercept. At the time points recommended for primary failure
      assessment according to the approved SmPCs, ustekinumab 45 mg (at week 28) also
      has the greatest probability of achieving PASI 50 response [RD 80.7%, 95%CI 77.2
      84.2%], followed by ustekinumab 90 mg, infliximab, adalimumab and etanercept.
      CONCLUSION: From a clinical practice perspective, and in terms of the most
      relevant efficacy measures (PASI 50 and PASI 75) and time points (end of
      induction phase [week 24] and time to assess primary failure as per the SmPCs),
      in the currently approved conditions of use ustekinumab is the most efficacious
      therapeutic alternative for moderate-to-severe plaque psoriasis, followed by
      infliximab, adalimumab and etanercept.

PMID- 24033852
TI  - Site of initial diabetes education does not affect metabolic outcomes in children
      with T1DM.
AB  - OBJECTIVE: To determine the difference in metabolic outcomes at 1 and 2 yr post
      type 1 diabetes mellitus (T1DM) diagnosis in children depending on the site of
      initial diabetes education: inpatient, vs. outpatient, vs. mixed locations.
      PATIENTS AND METHODS: A retrospective chart review was performed for all patients
      with new onset antibody positive T1DM, aged 1-18 yr old, diagnosed in 2004-2009,
      and followed for at least 1 yr in a diabetes program at a tertiary academic
      health care center. Patients were divided into three groups based on the site of
      initial diabetes education: inpatient, outpatient, and mixed locations. The
      primary outcome was A1c at 1 and 2 yr. RESULTS: We enrolled 238 children (133
      boys), mean (+/- SD) age 9.9 (+/- 4.1). A1c levels did not differ among
      inpatient, outpatient, and mixed location groups at 1 and 2 yr post diagnosis (p
      = 0.85 and p = 0.69, respectively) and the long-acting insulin doses were similar
      at 1 and 2 yr (p = 0.18 and p = 0.15, respectively). There was no difference in
      the number of acute diabetes complications between the groups. At 1 yr, 21.8% of
      outpatient-educated children were on insulin pump therapy in contrast to 14.7% of
      inpatient and 2.7% of mixed educated groups (p = 0.04). CONCLUSIONS: Families of
      children with new onset T1DM can be successfully and safely educated in a clinic
      setting. An 'education' admission for a medically stable patient is not necessary
      most of the time, however, clinical judgment and careful assessment of the
      family's coping and learning capabilities are important when determining the site
      of education.

PMID- 24033853
TI  - Microvascular invasion in small hepatocellular carcinoma: is it predictable with
      preoperative diffusion-weighted imaging?
AB  - BACKGROUND AND AIM: The presence of microvascular invasion (MVI) is an
      independent risk factor affecting recurrence-free survival following surgical
      treatment for small hepatocellular carcinoma (HCC). Our aim in this study was to
      investigate whether diffusion-weighted imaging (DWI) could be useful in
      predicting MVI for small HCC. METHODS: Breath-hold DWI (b-value 0, 500 s/mm(2) )
      and gadopentate dimeglumine-enhanced dynamic imaging of preoperative magnetic
      resonance imaging of 109 surgically proven small HCCs from 92 patients were
      retrospectively analyzed. The signal intensity ratio on DWI and apparent
      diffusion coefficients (ADCs) for lesions were quantitatively measured. Signal
      intensity ratio and ADC of DWI, tumor size, tumor shape, tumor capsule,
      peritumoral enhancement on arterial phase images, and dynamic enhancement pattern
      were analyzed as radiological parameters reflecting MVI and were compared with
      histopathological references. The chi-square test, Fisher's exact test, Mann
      Whitney U test, and the independent t-test were used for univariate analysis. To
      identify the independent predictors of MVI among these radiological parameters
      and to evaluate their diagnostic performance, multivariate logistic regression
      analysis and receiver operating characteristic curve analysis were performed,
      respectively. RESULTS: A univariate analysis showed that a lower ADC value (P =
      0.005) and irregular circumferential enhancement (P = 0.020) showed statistically
      significant associations with MVI. A multiple logistic regression analysis showed
      that the ADC value and irregular circumferential enhancement were independent
      predictors of MVI. With a cut-off of 1.227 * 10(-3)  mm(2) /s, the ADC value
      provided a sensitivity of 66.7% and a specificity of 78.6% in the prediction of
      MVI with an odds ratio of 7.63 (P < 0.01). CONCLUSIONS: Lower ADC values (< 1.227
      * 10(-3)  mm(2) /s) on DWI with b-value of 0.500 s/mm(2) can be a useful
      preoperative predictor of MVI for small HCCs.

PMID- 24033854
TI  - Enhanced production of Monacolin K by addition of precursors and surfactants in
      submerged fermentation of Monascus purpureus 9901.
AB  - The main problem in Monacolin K (MK) production by submerged fermentation of
      Monascus purpureus is low productivity. In this study, on one hand, addition of
      precursors was used to activate the biosynthesis of MK. When 4.0 g/L of sodium
      citrate was supplemented at the 48th H of the fermentation, the final MK
      production reached to 1,658.9 +/- 28.5 mg/L after 20 day of fermentation, which
      was improved by 52.6% compared with that of the control. On the other hand,
      addition of surfactants could increase the permeability of cell membrane, thus
      driving more intracellular metabolites secreted into the fermentation broth and
      alleviating the product inhibition. When 40.0 g/L of Triton X-100 was added at
      the beginning of the fermentation, the final MK production reached to 2,026.0 +/-
      30.4 mg/L after 20 day of fermentation, which was improved by 84.9% compared with
      that of the control. These results are helpful to provide some new insights into
      the biosynthetic regulation on MK production; the approach can be applied to
      other fungal fermentation processes for enhancing production of useful
      metabolites.

PMID- 24033855
TI  - The safety and efficacy of acute graft-versus-host disease prophylaxis with a
      higher target blood concentration of cyclosporine around 500 ng/mL.
AB  - Cyclosporine (CsA) is the most widely used immunosuppressive agent for the
      prevention of acute graft-versus-host disease (GVHD). In a previous report, the
      incidence of acute GVHD was decreased by increasing the target blood
      concentration of CsA during a continuous infusion from 300 to 500 ng/mL without
      excessive toxicities. To confirm these results, we retrospectively analyzed 69
      patients who received a continuous infusion of CsA at a higher target CsA level
      between 450 and 550 ng/mL (CsA500 group) and compared the clinical outcome with
      29 patients who received CsA with a lower target concentration between 250 and
      350 ng/mL (CsA300 group). The target concentration was determined based on the
      status of background diseases. Multivariate analysis revealed that the incidence
      of grade III-IV acute GVHD was significantly lower in the CsA500 group, although
      the incidence of grade II-IV acute GVHD was not different. Toxicities were
      equivalently observed between the two groups. Concomitant administration of
      voriconazole or itraconazole and higher hematocrit were identified as independent
      significant factors for higher concentration/dose ratio of CsA. The average dose
      of CsA to maintain CsA level around 500 ng/mL was higher compared with the
      previous study (3.4 mg/kg vs. 2.7 mg/kg at three wk), probably due to the
      difference in measuring method of CsA concentration. We conclude that continuous
      infusion of CsA with a target level between 450 and 550 ng/mL is a feasible and
      effective GVHD prophylaxis, but caution should be paid for the difference in
      measuring method.

PMID- 24033856
TI  - Comparison between computed tomography and (99m)TC- pertechnetate scintigraphy
      characteristics of the thyroid gland in cats with hyperthyroidism.
AB  - Scintigraphy is currently the reference standard for diagnosing feline
      hyperthyroidism; however, computed tomography (CT) is more widely available in
      veterinary practice. The purposes of this prospective study were to describe the
      CT appearance of thyroid glands in cats with hyperthyroidism and compare CT
      findings with findings from (99m) Tc-pertechnetate scintigraphy. Twenty-five
      adult hyperthyroid cats were included. Plain CT images were acquired for each cat
      and the following characteristics recorded for each thyroid lobe: visibility,
      delineation, position, attenuation, shape, and subjective size. Scintigraphic
      images were also acquired and the following characteristics recorded:
      radiopharmaceutical uptake, delineation, ectopic foci, shape, and subjective
      size. In CT images, thyroid lobes were most commonly found between the second and
      fourth cervical vertebrae, dorsolateral to the trachea. Affected thyroid lobes
      (based on scintigraphy reference standard) were most commonly oval and moderately
      enlarged in CT images. A heterogeneous attenuation pattern (isoattenuating to
      adjacent soft tissues with hypo- and hyperattenuating foci) was most commonly
      found in affected thyroid lobes. A positive correlation (P < 0.01) was identified
      between CT and scintigraphy for left-to-right thyroid lobe size relationship and
      subjective size of the larger thyroid lobe. The CT estimated mass was
      significantly higher (median = 148.8; range = [0;357.6]) for the more active
      thyroid lobe compared to the less active thyroid lobe (median = 84.6; range =
      [0;312.3]); (W = 154; P < 0.01). Findings indicated that CT may not reliably
      differentiate unilateral vs. bilateral hyperthyroidism in cats; however, CT may
      be a reliable alternative test for correctly identifying the more active thyroid
      lobe.

PMID- 24033857
TI  - Authors' reply: Combining two antibodies to define E-cadherin loss of expression
      in non-lobular breast carcinomas: when less is more.

PMID- 24033858
TI  - Promoter deletions of Klebsiella pneumoniae carbapenemase (KPC)-encoding genes
      (blaKPC -2) and efflux pump (AcrAB) on beta-lactam susceptibility in KPC
      producing Enterobacteriaceae.
AB  - Klebsiella pneumoniae carbapenemase (KPC)-encoding genes containing promoter
      deletions (bla(KPC-2a), bla(KPC-2b), and bla(KPC-2c) have disseminated in
      Enterobacteriaceae. The minimal inhibitory concentrations (MICs) to beta-lactams
      in clinical KPC-producing Enterobacteriaceae range from susceptible to high-level
      resistant, resulting in diagnostic problems. To better understand the variability
      in beta-lactam MICs among KPC-producing Enterobacteriaceae, three isoforms of
      bla(KPC-2) gene were used to transform Escherichia coli W4573 and its deletion
      mutant of an efflux pump (AcrAB) to examine the effects on beta-lactam
      susceptibility. MICs to beta-lactams in E. coli W4573 and its acrAB mutant strain
      increased 1- to 500-fold (MIC from 0.125 to 64 MUg mL(-1) of aztreonam) in the
      bla(KPC-2a), bla(KPC-2b), and bla(KPC-2c) transformants compared with the cloning
      vector alone. However, transformants of the acrAB mutant strain remained
      susceptible to all beta-lactams tested except for aztreonam and carbenicillin.
      Levels of the three promoters' length and carbapenemase activities in the
      transformants harboring the bla(KPC-2a), bla(KPC-2b), and bla(KPC-2c) were
      correlated to the levels of beta-lactam MICs in both E. coli W4573 and its mutant
      of an efflux pump (AcrAB). Overall, these results suggest that promoter-deletions
      of bla(KPC-2) gene and AcrAB may be associated with the variability in beta
      lactam MICs in KPC-producing Enterobacteriaceae.

PMID- 24033860
TI  - Fingerprint CD34 immunopositivity to distinguish neurofibroma from an
      early/paucicellular desmoplastic melanoma can be misleading.

PMID- 24033859
TI  - Sulphur-oxidizing and sulphate-reducing communities in Brazilian mangrove
      sediments.
AB  - Mangrove soils are anaerobic environments rich in sulphate and organic matter.
      Although the sulphur cycle is one of the major actors in this ecosystem, little
      is known regarding the sulphur bacteria communities in mangrove soils. We
      investigated the abundance, composition and diversity of sulphur-oxidizing (SOB)
      and sulphate-reducing (SRB) bacteria in sediments from three Brazilian mangrove
      communities: two contaminated, one with oil (OilMgv) and one with urban waste and
      sludge (AntMgv), and one pristine (PrsMgv). The community structures were
      assessed using quantitative real-time polymerase chain reaction (qPCR),
      polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and
      clone libraries, using genes for the enzymes adenosine-5'-phosphosulphate
      reductase (aprA) and sulphite reductase (Dsr) (dsrB). The abundance for qPCR
      showed the ratio dsrB/aprA to be variable among mangroves and higher according to
      the gradient observed for oil contamination in the OilMgv. The PCR-DGGE patterns
      analysed by Nonmetric Multidimensional Scaling revealed differences among the
      structures of the three mangrove communities. The clone libraries showed that
      Betaproteobacteria, Gammaproteobacteria and Deltaproteobacteria were the most
      abundant groups associated with sulphur cycling in mangrove sediments. We
      conclude that the microbial SOB and SRB communities in mangrove soils are
      different in each mangrove forest and that such microbial communities could
      possibly be used as a proxy for contamination in mangrove forests. 

PMID- 24033861
TI  - Oral l-ornithine-l-aspartate in minimal hepatic encephalopathy: A randomized,
      double-blind, placebo-controlled trial.
AB  - AIM: Evaluate efficacy/safety of oral l-ornithine-l-aspartate (LOLA) in
      controlling minimal hepatic encephalopathy (MHE). METHODS: Consecutive cirrhotic
      outpatients with MHE (defined by psychometric number connection tests A/B [NCT
      A/B] and digit symbol substitution test [DSST] score of >2 standard deviations)
      were randomized to a 60-day oral LOLA (5 g t.i.d) or placebo group. Critical
      flicker frequency test (CFF), quantitative electroencephalogram (qEEG), arterial
      ammonia (NH3), Beck's anxiety-depression forms and liver disease quality of life
      (LD-QOL) were assessed. Patients were followed for 6 months after the end of the
      study to assess LOLA prophylactic role on overt hepatic encephalopathy (OHE).
      RESULTS: Sixty-four patients were included, 63 (98.4%) with MHE. In six of these
      patients, CFT was less than 39 Hz (9.52%); NH3 was increased in 32 (50.8%); 25%
      had abnormal qEEG. Age, sex, scholarship, Child-Pugh (CP), Model for End-Stage
      Liver Disease, NCT-A/B, DSST, CFF and NH3 were similar in both groups at the
      baseline. LOLA led to a significant improvement in NCT-B age-controlled z-score
      (3.4 +/- 3.4 vs 1.5 +/- 2.3, P = 0.01) and CFF (42.2 +/- 5.8 vs 45.2 +/- 5.8, P =
      0.02), comparing the first and the last visit, but there were no differences
      between LOLA and placebo regarding the whole psychometric battery, CFF, LD-QOL
      and Beck's forms. No serious adverse effects occurred. Patients taking LOLA had
      less episodes of OHE at 6 months (5% vs 37.9%, P = 0.016), as they have
      significant improvement on liver function assessed by CP (P < 0.001). CONCLUSION:
      A 60-day oral LOLA course was not better than placebo in treating MHE, but was
      useful in preventing further episodes of OHE.

PMID- 24033862
TI  - Ethnic differences in objective and subjective skin irritation response: an
      international study.
AB  - BACKGROUND: Due to global marketing in the cosmetics industry, it is important to
      assess ethnic population susceptibility when evaluating the safety of cosmetic
      products or chemicals. OBJECTIVES: To investigate ethnic variations in skin
      irritation response to positive irritants. METHODS: Clinical testing was
      performed in four countries on two ethnic groups - Asian and Caucasian. We
      performed patch tests on the subjects' back with 0.5% aqueous sodium lauryl
      sulfate (SLS) and 0.15% retinol prepared in 1,3-butylene glycol. Stinging tests
      were performed using 5% aqueous lactic acid and 0.001% (w/v) capsaicin prepared
      in 10% ethanol solution separately. RESULTS: The incidence of self-perceived skin
      sensitivity was similar in the two ethnic groups. However, the incidence of
      adverse skin reaction to cosmetics appeared significantly higher in Asian (33.0%)
      than in Caucasian subjects (11.3%). For standard positive irritants such as 0.5%
      aqueous SLS solution, Asian subjects showed significantly higher scores than
      Caucasian subjects. The incidence of positive reaction to the 0.15% retinol patch
      test tended to be higher in Asian than in Caucasian subjects. Our data also
      showed that neurosensitivity to 5% lactic acid and 0.001% capsaicin was higher in
      Asian than in Caucasian subjects. CONCLUSION: Although self-reported skin
      sensitivity does not appear to differ according to ethnicity, there are ethnic
      differences in objective and subjective skin irritation responses to several
      standard positive materials.

PMID- 24033864
TI  - Socioeconomic disparities of periodontitis in Koreans based on the KNHANES IV.
AB  - OBJECTIVES: The aim of this study was to identify the socioeconomic factors
      associated with the prevalence of periodontitis in Koreans. METHODS: Cross
      sectional data from 12 763 subjects, 15 years old and above, who underwent
      periodontal examinations were obtained from the Korean National Health and
      Nutrition Examination Survey IV (2007-209). Multivariate linear and logistic
      regression analyses were applied to estimate the association between
      socioeconomic indicators and prevalence of periodontitis. RESULTS: A significant
      association was found between increasing age and periodontitis. Participants with
      higher income were less likely to have periodontitis (aOR = 0.9 and 95% CI = 0.78
      0.98, and aOR = 0.7 and 95% CI = 0.60-0.80 in the middle and highest quintiles of
      monthly household income, respectively). In addition, participants living in
      rural areas were less likely to have periodontitis (aOR = 0.9 and 95% CI = 0.81
      0.99), and current smokers were more likely to have periodontitis (aOR = 1.7 and
      95% CI = 1.49-1.89). The analysis of comorbidities revealed that individuals with
      diabetes mellitus (DM) were significantly more likely to have periodontitis (aOR
      = 1.4 and 95% CI = 1.18-1.68). CONCLUSIONS: In a rapidly increasing Korean
      population, the lower socioeconomic groups as well as individuals with DM were
      significantly more likely to present with periodontitis.

PMID- 24033863
TI  - Composite efficacy parameters and predictors of hypoglycaemia in basal-plus
      insulin therapy--a combined analysis of 713 type 2 diabetic patients.
AB  - AIMS: We aimed to identify predictors of hypoglycaemia in patients with poorly
      controlled type 2 diabetes treated with a single daily bolus of insulin glulisine
      on top of insulin glargine and oral antidiabetic drugs (basal-plus regimen).
      METHODS: We retrospectively analysed four large basal-plus trials including 713
      patients (47% female) with type 2 diabetes, mean age of 59.9 +/- 9.5 years and
      diabetes duration of 11 +/- 7.0 years. Predictors for symptomatic, severe and
      nocturnal hypoglycaemia were identified by multivariate logistic regression
      analyses, calculation of odds ratios (ORs) and Wald 95% confidence intervals
      (CIs). RESULTS: Mean numbers of hypoglycaemic events per year were 4.64 +/- 11.4
      (symptomatic < 60 mg/dl), 0.59 +/- 2.28 (nocturnal) and 0.03 +/- 0.22 (severe). A
      total of 44.5% of patients reached the composite endpoint of glycated haemoglobin
      (HbA1c) <7.0% plus no severe hypoglycaemia, and 26.7% reached the composite of
      HbA1c <7.0% plus no symptomatic hypoglycaemia. Predictors of nocturnal and
      symptomatic hypoglycaemia were female gender (OR 1.82; 95% CI 1.07-3.11 and OR
      1.89; 95% CI 1.31-2.78), diabetes duration >10 versus <5 years (OR 2.61; 95% CI
      1.03-6.59 and OR 2.01; 95% CI 1.15-3.51) and higher basal insulin dose (per unit
      of increase) (OR 1.01; 95% CI 1.00-1.03 and OR 1.01; 95% CI 1.00-1.02).
      Conversely, a higher body mass index (BMI) (27-30 vs. <27 kg/m(2) and >30 vs. <27
      kg/m(2) ) conferred a reduced risk of symptomatic hypoglycaemia with an OR of
      0.53 (95% CI 0.31-0.90) and an OR of 0.61 (95% CI 0.39-0.97). CONCLUSIONS: Female
      gender, a long diabetes duration and higher basal insulin dose were predictors of
      hypoglycaemia, while protection was provided by BMI > 30. These results may help
      to successfully establish basal-plus insulin regimen in individual patients on
      their transition from basal-only to basal-bolus treatment.

PMID- 24033865
TI  - Ten-day Quadruple therapy comprising proton-pump inhibitor, bismuth,
      tetracycline, and levofloxacin achieves a high eradication rate for Helicobacter
      pylori infection after failure of sequential therapy.
AB  - BACKGROUND: Sequential therapy has been recommended in the Maastricht IV/Florence
      Consensus Report as the first-line treatment for Helicobacter pylori eradication
      in regions with high clarithromycin resistance. However, it fails in 5-24% of
      infected subjects, and the recommended levofloxacin-containing triple rescue
      therapy only achieves a 77% eradication rate after failure of sequential therapy.
      AIM: To investigate the efficacy of a novel quadruple therapy comprising proton
      pump inhibitor, bismuth, tetracycline, and levofloxacin for rescue treatment of
      sequential therapy. METHODS: This was a multicenter study in which H. pylori
      infected patients who had failed sequential therapy received a 10-day quadruple
      therapy (esomeprazole (40 mg b.d), tripotassium dicitrato bismuthate (120 mg
      q.d.s.), tetracycline (500 mg q.d.s.), and levofloxacin (500 mg o.d.) for 10
      days). H. pylori status was examined 6 weeks after the end of treatment. RESULTS:
      From July 2007 to June 2012, twenty-four subjects received 10-day quadruple
      therapy. The eradication rates according to intention-to-treat and per-protocol
      analyses were both 95.8% (23 of 24; 95% confidence interval, 87.8-103.8%).
      Adverse events were seen in 25.0% (6 of 24) of the patients. Drug compliance was
      100.0% (24/24). CONCLUSIONS: The 10-day quadruple therapy comprising proton-pump
      inhibitor, bismuth, tetracycline, and levofloxacin achieves a very high
      eradication rate for H. pylori infection after failure of sequential therapy. It
      is well tolerated and has great potential to become a good choice of rescue
      treatment following non-bismuth-containing quadruple therapy in regions with high
      clarithromycin resistance.

PMID- 24033866
TI  - Comparing accuracy of the Yale swallow protocol when administered by registered
      nurses and speech-language pathologists.
AB  - AIMS AND OBJECTIVES: (1) To describe the results of a web-based teaching module
      used by registered nurses to identify patients at risk of aspiration and (2) to
      determine accuracy of the registered nurse-administered 3-ounce water swallow
      challenge protocol, that is, drinking three ounces of water, a basic cognitive
      screen and oral mechanism evaluation, when compared with blinded ratings from
      speech-language pathology. BACKGROUND: Early identification of potential
      swallowing problems is important prior to ingestion of food, fluid and
      medications. Unfortunately, current nurse-administered screens use a variety of
      non-evidence-based assessments. It would be beneficial to use a valid, reliable
      and evidence-based screen, that is, the Yale swallow protocol. DESIGN:
      Prospective, blinded, referral-based. METHODS: Fifty-two registered nurses and
      101 inpatients participated. First, each participant was administered the 3-ounce
      water swallow challenge protocol by a speech-language pathologist. Second, a
      nurse administered the protocol to the same patient within one hour and
      independently recorded results and diet recommendations. The nurse was blinded to
      the study's purpose and results of the speech-language pathologist's initial
      screening. Out of view, but simultaneous with the nurse-administered protocol, a
      speech-language pathologist rerated the patient's challenge for comparison with
      initial results and determined the accuracy of the nurse-administered protocol.
      RESULTS: Intra- and inter-rater protocol agreements for the two speech-language
      pathologists were 100%. Inter-rater protocol agreement between registered nurses
      and speech-language pathologists was 98.01%. CONCLUSIONS: Results confirm the
      reliability and accuracy of a registered nurse-administered Yale swallow
      protocol. The consequence of 98% accuracy combined with previously reported 96.5%
      sensitivity, 97.9% negative predictive value and <2% false negative rate allowed
      for adoption of the protocol for the entire general hospital population.
      RELEVANCE TO CLINICAL PRACTICE: Avoidance of preventable prandial pulmonary
      aspiration as a cause of nosocomial infection is an important goal for all acute
      care hospitalised patients deemed at risk of aspiration.

PMID- 24033868
TI  - Detection of chronic obstructive pulmonary disease in community-based annual lung
      cancer screening: Chiba Chronic Obstructive Pulmonary Disease Lung Cancer
      Screening Study Group.
AB  - BACKGROUND AND OBJECTIVE: Detection of chronic obstructive pulmonary disease
      (COPD) is crucial in the management of COPD. The aim of this study was to
      establish the utility of a community-based lung cancer screening for detecting
      COPD. METHODS: In Japan, community-based lung cancer screening for residents who
      are 40 years or older using chest radiography is well established. A screening
      system in Chiba City, Japan, was used to detect COPD. The criteria to consider
      COPD at screening included age of 60 years or older, a smoking history and
      chronic respiratory symptoms. Participants fulfilling these criteria were
      referred for diagnostic evaluation consisting of pulmonary function testing (PFT)
      and chest computed tomography (CT). RESULTS: Of 89,100 Chiba City residents who
      underwent lung cancer screening, 72,653 residents were 60 years or older. Among
      them, 878 (1.0%) were identified with suspected COPD and referred for further
      evaluation. Of those identified, a total of 567 residents (64.6%, 567/878)
      underwent further evaluations, and 161 (28.4%) were reported to have COPD, with
      38.5% of them requiring COPD treatment. To verify the diagnoses from the
      secondary evaluation centres, PFT and CT data were collected from 228 study
      participants, and 24.9% were diagnosed with COPD. CT findings classified
      according to the Goddard classification revealed that 20.1% of these participants
      had moderate to severe emphysema. CONCLUSIONS: COPD screening added to a
      community-based lung cancer screening programme may be effective in the detection
      of patients with COPD.

PMID- 24033867
TI  - A rice lectin receptor-like kinase that is involved in innate immune responses
      also contributes to seed germination.
AB  - Seed germination and innate immunity both have significant effects on plant life
      spans because they control the plant's entry into the ecosystem and provide
      defenses against various external stresses, respectively. Much ecological
      evidence has shown that seeds with high vigor are generally more tolerant of
      various environmental stimuli in the field than those with low vigor. However,
      there is little genetic evidence linking germination and immunity in plants.
      Here, we show that the rice lectin receptor-like kinase OslecRK contributes to
      both seed germination and plant innate immunity. We demonstrate that knocking
      down the OslecRK gene depresses the expression of alpha-amylase genes, reducing
      seed viability and thereby decreasing the rate of seed germination. Moreover, it
      also inhibits the expression of defense genes, and so reduces the resistance of
      rice plants to fungal and bacterial pathogens as well as herbivorous insects.
      Yeast two-hybrid and co-immunoprecipitation experiments revealed that OslecRK
      interacts with an actin-depolymerizing factor (ADF) in vivo via its kinase
      domain. Moreover, the rice adf mutant exhibited a reduced seed germination rate
      due to the suppression of alpha-amylase gene expression. This mutant also
      exhibited depressed immune responses and reduced resistance to biotic stresses.
      Our results thus provide direct genetic evidence for a common physiological
      pathway connecting germination and immunity in plants. They also partially
      explain the common observation that high-vigor seeds often perform well in the
      field. The dual effects of OslecRK may be indicative of progressive adaptive
      evolution in rice. 

PMID- 24033869
TI  - Rates of new infections in British Columbia continue to decline at a faster rate
      than in other Canadian regions.

PMID- 24033870
TI  - The nature and origin of nucleus-like intracellular inclusions in
      Paleoproterozoic eukaryote microfossils.
AB  - The well-known debate on the nature and origin of intracellular inclusions (ICIs)
      in silicified microfossils from the early Neoproterozoic Bitter Springs Formation
      has recently been revived by reports of possible fossilized nuclei in
      phosphatized animal embryo-like fossils from the Ediacaran Doushantuo Formation
      of South China. The revisitation of this discussion prompted a critical and
      comprehensive investigation of ICIs in some of the oldest indisputable eukaryote
      microfossils-the ornamented acritarchs Dictyosphaera delicata and
      Shuiyousphaeridium macroreticulatum from the Paleoproterozoic Ruyang Group of
      North China-using a suite of characterization approaches: scanning electron
      microscopy (SEM), transmission electron microscopy (TEM), and focused ion beam
      scanning electron microscopy (FIB-SEM). Although the Ruyang acritarchs must have
      had nuclei when alive, our data suggest that their ICIs represent neither
      fossilized nuclei nor taphonomically condensed cytoplasm. We instead propose that
      these ICIs likely represent biologically contracted and consolidated eukaryotic
      protoplasts (the combination of the nucleus, surrounding cytoplasm, and plasma
      membrane). As opposed to degradational contraction of prokaryotic cells within a
      mucoidal sheath-a model proposed to explain the Bitter Springs ICIs-our model
      implies that protoplast condensation in the Ruyang acritarchs was an in vivo
      biologically programmed response to adverse conditions in preparation for
      encystment. While the discovery of bona fide nuclei in Paleoproterozoic
      acritarchs would be a substantial landmark in our understanding of eukaryote
      evolution, the various processes (such as degradational and biological
      condensation of protoplasts) capable of producing nuclei-mimicking structures
      require that interpretation of ICIs as fossilized nuclei be based on
      comprehensive investigations. 

PMID- 24033871
TI  - The prevalence of onychomycosis in psoriatic patients: a systematic review.
AB  - We systematically reviewed all available literature concerning the prevalence of
      onychomycosis in patients with nail psoriasis and the distribution of pathogens
      causing onychomycosis in this specific group of patients. Databases searched were
      Pubmed, EMBASE and the Cochrane Controlled Clinical Trial Register. All studies
      reporting on the prevalence of onychomycosis in nail psoriasis were obtained, and
      quality assessment was determined by the STrengthening the Reporting of
      OBservational studies in Epidemiology checklist. Literature search revealed 720
      studies, of which 10 studies met the inclusion criteria. The major limitation of
      the review was the heterogeneity of the included studies, which prevented the
      possibility to conduct a meta analysis. However, the average prevalence of 18.0%
      of onychomycosis in psoriatic patients seems to be increased when compared with
      control groups and literature on healthy population, even though the ultimate
      evidence remains lacking. As in the literature hypothesized shift in causative
      agents from dermatophytes to yeasts and/or moulds could not be confirmed. The
      clinical consequence of the relatively high prevalence of onychomycosis in
      psoriasis may be a general advice to rule out onychomycosis or concomitant
      onychomycosis in these patients with (suspected) nail psoriasis. This advice is
      stressed by the relative simplicity of treating the contribution of onychomycosis
      in the nail dystrophy but also the fact that nail psoriasis mostly is treated by
      immunosuppressive drugs, like steroids, methotrexate or biologics which may
      aggravate mycotic nail infections. 

PMID- 24033872
TI  - Transformation of admission interview to documentation for nursing practice.
AB  - The admission interview is usually the first structured meeting between patient
      and nurse. The interview serves as the basis for personalised nursing and care
      planning and is the starting point for the clinic's documentation of the patient
      and his course of treatment. In this way, admission interviews constitute a basis
      for reporting by each nurse on the patient to nursing colleagues. This study
      examined how, by means of the admission interview, nurses constructed written
      documentation of the patient and his course of treatment for use by fellow
      nurses. A qualitative case study inspired by Ricoeur was conducted and consisted
      of five taped admission interviews, along with the written patient documentation
      subsequently worked out by the nurse. The findings were presented in four
      constructed themes: Admission interviews are the nurse's room rather than the
      patient's; Information on a surgical object; The insignificant but necessary
      contact; and Abnormalities must be medicated. It is shown how the nurse's
      documentation was based on the admission interview, the medical record details on
      the patient (facts that are essential to know in relation to disease and
      treatment), as well as the nurse's preconception of how to live a good life, with
      or without disease. Often, the patient tended to become an object in the nurse's
      report. It is concluded that in practice, the applied documentation system, VIPS,
      comes to act as the framework for what is important to the nurse to document
      rather than a tool that enables her to document what is important to the
      individual patient and his special circumstances and encounter with the health
      system. 

PMID- 24033874
TI  - Splenic lymph follicles generate immunoglobulin M-producing B cells in primary
      biliary cirrhosis.
AB  - AIM: To reveal the site of immunoglobulin (Ig)M production in primary biliary
      cirrhosis (PBC) we performed immunohistochemical analysis on spleens collected
      from patients with PBC. METHODS: Splenic tissue samples were collected at the
      time of the autopsy from patients with hepatic failure. Immunostaining for IgM,
      CD21 and CXCL13 were performed using the splenic tissue samples. RESULTS: The
      samples from five out of eight cases with PBC but not in eight cases of chronic
      hepatitis C virus infection showed accumulation of IgM positive cells in CD21
      positive lymph follicles. The CXCL13 positive cells also accumulated in the
      center of the lymph follicles where the IgM positive cells accumulated.
      CONCLUSION: The present results suggest that excess IgM is produced from the
      spleen of PBC. Furthermore, it was suggested that CXCL13 positive follicular
      dendritic cells possibly contribute to this process.

PMID- 24033873
TI  - The threat of disease increases as species move toward extinction.
AB  - At local scales, infectious disease is a common driver of population declines,
      but globally it is an infrequent contributor to species extinction and
      endangerment. For species at risk of extinction from disease important questions
      remain unanswered, including when does disease become a threat to species and
      does it co-occur, predictably, with other threats? Using newly compiled data from
      the International Union for Conservation of Nature (IUCN) Red List, we examined
      the relative role and co-occurrence of threats associated with amphibians, birds,
      and mammals at 6 levels of extinction risk (i.e., Red List status categories:
      least concern, near threatened, vulnerable, endangered, critically endangered,
      and extinct in the wild/extinct). We tested the null hypothesis that the
      proportion of species threatened by disease is the same in all 6 Red List status
      categories. Our approach revealed a new method for determining when disease most
      frequently threatens species at risk of extinction. The proportion of species
      threatened by disease varied significantly between IUCN status categories and
      linearly increased for amphibians, birds, and all species combined as these taxa
      move from move from least concern to critically endangered. Disease was
      infrequently the single contributing threat. However, when a species was
      negatively affected by a major threat other than disease (e.g., invasive species,
      land-use change) that species was more likely to be simultaneously threatened by
      disease than species that had no other threats. Potential drivers of these trends
      include ecological factors, clustering of phylogenetically related species in Red
      List status categories, discovery bias among species at greater risk of
      extinction, and availability of data. We echo earlier calls for baseline data on
      the presence of parasites and pathogens in species when they show the first signs
      of extinction risk and arguably before. La Amenaza de Enfermedades Incrementa a
      Medida que las Especies se Aproximan a la Extincion. 

PMID- 24033875
TI  - Low back pain and associated imaging findings among HIV-infected patients
      referred to an HIV/palliative care clinic.
AB  - BACKGROUND: Low back pain is a common cause of chronic pain in human
      immunodeficiency virus (HIV)-infected patients. The American College of
      Physicians and American Pain Society guidelines for diagnostic imaging in low
      back pain are difficult to apply to patients with chronic illnesses like HIV who
      may have risk factors for cancer or compression fractures, but whether imaging
      all such patients for low back pain improves outcomes is unknown. OBJECTIVE: Our
      objective was to describe patients referred to a chronic pain-focused
      HIV/palliative care clinic (HPCC) with back pain and their associated lumbar
      spine imaging findings. METHODS: We conducted a retrospective chart review of
      patients at a palliative care clinic that sees patients with HIV, most of whom
      have chronic pain. Charts with a diagnosis of low back pain were cross-referenced
      with an imaging database and any magnetic resonance imaging (MRI) of the lumbar
      spine with or without contrast were identified. RESULTS: Seventy-six of 137
      patients referred to the HPCC were found to have back pain. These patients were
      mainly young (median age 45, interquartile range 40-51) with well-controlled HIV.
      Twenty-two (29%) of these patients had an MRI of the lumbar spine, and 11 (50%)
      of these warranted follow-up, most of whom had degenerative disc disease,
      including four with findings concerning for malignancy. DISCUSSION: This is the
      first study to explore the role of spinal imaging in HIV-infected patients. In
      our study, four patients had findings concerning for malignancy. These findings
      suggest that spinal imaging should be considered in the work up of HIV-infected
      patients with moderate to severe back pain.

PMID- 24033877
TI  - Biosorption and biotransformation of fluoranthene by the white-rot fungus
      Pleurotus eryngii F032.
AB  - Major concern about the presence of fluoranthene, which consists of four fused
      benzene rings, in the environment has been raised in the past few years due to
      its toxic, mutagenic, and persistent organic pollutant properties. In this study,
      we investigated the removal of fluoranthene under static and agitated conditions.
      About 89% fluoranthene was removed within 30 days under the agitated condition,
      whereas under the static condition, only 54% fluoranthene was removed. We further
      investigated the behavior and mechanism of fluoranthene biosorption and
      biotransformation by Pleurotus eryngii F032 to accelerate the elimination of
      fluoranthene. The optimum conditions for the elimination of fluoranthene by P.
      eryngii F032 included a temperature of 35  degrees C, pH 3, 0.2% inoculum
      concentration, and a C/N ratio of 16. Under these conditions at the initial
      fluoranthene concentration of 10 mg/L, more than 95% of fluoranthene was
      successfully removed within 30 days. Of those factors influencing the
      biodegradation of fluoranthene, salinity, glucose, and rhamnolipid content were
      of the greatest importance. Degradation metabolites identified using gas
      chromatography-mass spectrometry were 1-naphthalenecarboxylic acid and salicylic
      acid, suggesting possible metabolic pathways. Finally, it can be presumed that
      the major mechanism of fluoranthene elimination by white-rot fungi is to
      mineralize polycyclic aromatic hydrocarbons via biotransformation enzymes like
      laccase.

PMID- 24033876
TI  - Serum Helicobacter pylori CagA antibody titer as a useful marker for advanced
      inflammation in the stomach in Japan.
AB  - BACKGROUND AND AIM: Subjects infected with Helicobacter pylori containing cagA do
      not always induce serum CagA antibody. Our previous meta-analysis showed that
      serum CagA seropositivity was associated with gastric cancer even in East Asian
      countries. However, it remains unclear why serum CagA-positive status is
      associated with gastric cancer. In this study, we aimed to examine the
      relationship between anti-CagA antibody titer and the levels of pepsinogen (PG),
      and histological score. METHODS: Eighty-eight H. pylori-positive Japanese
      patients with gastritis were included. Serum CagA antibody titer, PG I, and PG II
      were evaluated by ELISA. Histological scores were evaluated according to Update
      Sydney System. CagA expression was examined by immunoblot. RESULTS:
      Seroprevalence of CagA antibody was found in 75.0%. Interestingly, serum CagA
      antibody titer was significantly correlated with PG I and PG II levels (P = 0.003
      and 0.004, respectively). Serum CagA antibody titer was also significantly
      correlated with mucosal inflammation in the corpus (P = 0.04). On the other hand,
      bacterial density was not related with CagA antibody titer. CagA expression level
      of the strains was irrespective of the status of PG and serum CagA antibody.
      CONCLUSIONS: Subjects with higher serum CagA antibody titer can be considered as
      high-risk population for the development of gastric cancer from the point of
      strong gastric inflammatory response even in Japan. Host recognition rather than
      bacterial colonization might be associated with the difference of serum CagA
      antibody titer.

PMID- 24033878
TI  - Development and validation of the Burdens in Oral Surgery Questionnaire (BiOS-Q).
AB  - Patients' perspective is increasingly re-cognised as an important outcome measure
      in oral surgery. However, how patients perceive the surgical treatment cannot be
      assessed currently. This would be an important indicator for process-related
      quality of care. It was the aim to develop and to validate an instrument for the
      assessment of patient-based measures of process-related quality of care in oral
      surgery. The new Burdens in Oral Surgery Questionnaire (BiOS-Q) was developed in
      two steps in patients undergoing oral surgery. First, an item pool was created
      using semi-structured interviews in 90 patients. Second, a preliminary version
      was applied in 297 consecutively recruited patients to assess redundancy,
      completion rates, face validity, difficulty and distribution. Psychometric
      properties of the final version of the questionnaire were evaluated. The BiOS-Q
      consists of 16 items and showed satisfactory internal consistency (Cronbach's
      alpha = 0.84) and excellent test-retest reliability (ICC = 0.90). The
      questionnaire's mean score was significantly correlated with dentists' burdens (r
      = 0.44) and patients' overall satisfaction (r = 0.39) indicating sufficient
      validity. The BiOS-Q is a reliable and valid instrument for the assessment of
      patient-based process-related quality of care in oral surgery.

PMID- 24033879
TI  - Endoscopic ultrasound-guided tissue acquisition.
AB  - Endoscopic ultrasound (EUS) is an indispensable tool for tissue acquisition in
      patients with gastrointestinal tumors. While fine-needle aspiration (FNA) has
      been routinely carried out for establishing tissue diagnosis, the emerging
      concept of tailoring chemotherapeutic agents based on molecular markers has
      increased the demand for core tissue procurement by means of EUS-guided fine
      needle biopsy (EUS-FNB). In addition, FNB may offset the limitations of FNA
      wherein the diagnostic sensitivity is incumbent on the availability of an onsite
      cytopathologist. Given the increasing number of procedures being done, developing
      a unit-specific algorithmic approach for needle selection is important to improve
      the procedural efficiency and utilization of resources. Finally, the best
      outcomes can be attained only by practicing evidence-based techniques, procuring
      adequate quantity of sample for ancillary studies and processing the specimens
      appropriately.

PMID- 24033880
TI  - Japanese guidance for use of biologics for psoriasis (the 2013 version).
AB  - The clinical use of adalimumab and infliximab, human anti-tumor necrosis factor
      (TNF)-alpha monoclonal antibodies, for psoriasis began in January 2010. In
      January 2011, ustekinumab, a human anti-interleukin-12/23p40 (IL-12/23p40)
      monoclonal antibody, was newly approved as the third biologic with an indication
      for psoriasis. While all of these biologics are expected to exhibit excellent
      therapeutic effect for psoriasis and to contribute to the improvement of quality
      of life in patients, these drugs require careful safety measures to prevent
      adverse drug reactions, such as serious infections. The new guidance, an English
      version prepared by revising the Japanese Guidance/Safety Manual for Use of
      Biologics for Psoriasis 2011 (in Japanese), is intended to provide up-to-date,
      evidence-based recommendations and safety measures on the use of biologics, and
      describes the optimal use of the three biologics, medical requirements for
      facilities for using biologics, details of safety measures against reactivation
      of tuberculosis and hepatitis B virus infection, and recommendable combination
      therapies with biologics. 

PMID- 24033881
TI  - Vertical mother-neonate transfer of maternal gut bacteria via breastfeeding.
AB  - Breast milk has recently been recognized as source of commensal and potential
      probiotic bacteria. The present study investigated whether viable strains of gut
      associated obligate anaerobes are shared between the maternal and neonatal gut
      ecosystem via breastfeeding. Maternal faeces, breast milk and corresponding
      neonatal faeces collected from seven mothers-neonate pairs at three neonatal
      sampling points were analyzed by culture-independent (pyrosequencing) and culture
      dependent methods (16S rRNA gene sequencing, pulsed field gel electrophoresis,
      random amplified polymorphic DNA and repetitive extragenic palindromic polymerase
      chain reaction. Pyrosequencing allowed identifying gut-associated obligate
      anaerobic genera, like Bifidobacterium, Bacteroides, Parabacteroides and members
      of the Clostridia (Blautia, Clostridium, Collinsella and Veillonella) shared
      between maternal faeces, breast milk and neonatal faeces. Using culture, a viable
      strain of Bifidobacterium breve was shown to be shared between all three
      ecosystems within one mother-neonate pair. Furthermore, pyrosequencing revealed
      that several butyrate-producing members of the Clostridia (Coprococcus,
      Faecalibacterium, Roseburia and Subdoligranulum) were shared between maternal
      faeces and breast milk. This study shows that (viable) obligate gut-associated
      anaerobes may be vertically transferred from mother to neonate via breastfeeding.
      Thus, our data support the recently suggested hypothesis of a novel way of mother
      neonate communication, in which maternal gut bacteria reach breast milk via an
      entero-mammary pathway to influence neonatal gut colonization and maturation of
      the immune system. 

PMID- 24033882
TI  - Effects of 24-epibrassinolide on plant growth, osmotic regulation and ion
      homeostasis of salt-stressed canola.
AB  - This study evaluated effects of foliar spraying 24-epibrassinoide (24-EBL) on the
      growth of salt-stressed canola. Seedlings at the four-leaf stage were treated
      with 150 mM NaCl and different concentrations of 24-EBL (10(-6), 10(-8), 10(-10),
      10(-12) M) for 15 days. A concentration of 10(-10) M 24-EBL was chosen as optimal
      and used in a subsequent experiment on plant biomass and leaf water potential
      parameters. The results showed that 24-EBL mainly promoted shoot growth of salt
      stressed plants and also ameliorated leaf water status. Foliar spraying of salt
      stressed canola with 24-EBL increased osmotic adjustment ability in all organs,
      especially in younger leaves and roots. This was mainly due to an increase of
      free amino acid content in upper leaves, soluble sugars in middle leaves, organic
      acids and proline in lower leaves, all of these compounds in roots, as well as
      essential inorganic ions. Na(+) and Cl(-) sharply increased in different organs
      under salt stress, and 24-EBL reduced their accumulation. 24-EBL improved the
      uptake of K(+), Ca(2+), Mg(2+) and NO3(-) in roots, which were mainly transported
      to upper leaves, while NO3(-) was mainly transported to middle leaves. Thus, 24
      EBL improvements in ion homeostasis of K(+)/Na(+), Ca(2+)/Na(+), Mg(2+)/Na(+) and
      NO3(-)/Cl(-), especially in younger leaves and roots, could be explained. As most
      important parts, younger leaves and roots were the main organs protected by 24
      EBL via improvement in osmotic adjustment ability and ion homeostasis. Further,
      physiological status of growth of salt-stressed canola was ameliorated after 24
      EBL treatment.

PMID- 24033883
TI  - Placental abnormalities detected by ultrasonography in a case of confined
      placental mosaicism for trisomy 2 with severe fetal growth restriction.
AB  - Clinical outcome of confined placental mosaicism (CPM) is varied, from normal
      pregnancy to intrauterine fetal death. It has been suggested that CPM for trisomy
      2 is less likely to cause serious adverse effect on pregnancy. We hereby report a
      case of CPM for trisomy 2, which presented severe fetal growth restriction (FGR)
      and placental abnormalities. A 30-year-old woman was referred to our hospital at
      17+2 weeks because of marked FGR. Ultrasonography demonstrated prominent
      placental hypertrophy with multiple focal defects without any fetal structural
      abnormalities. Amniocentesis at 18+3 weeks revealed normal karyotype. Fetal
      growth rate worsened with gestational weeks, reaching -7 standard deviation at 36
      weeks. At 37 weeks, the fetal condition suddenly deteriorated, ending in a
      stillbirth of a 756-g female baby. Postnatal cytogenetic analysis by array
      comparative genomic hybridization revealed trisomy 2 of the chorionic villi, and
      CPM for trisomy 2 was suggested as the cause of FGR and placental abnormalities.

PMID- 24033884
TI  - Wireless communication in clinical environments with unique needs.
AB  - Wireless technology in healthcare has been associated with communication-related
      improvements in workflow; however, there are barriers to adoption. This study
      examined predictors of use of wireless communication devices (WCDs) in
      environments with unique needs (i.e., intensive care unit [ICU]). Nurses were
      recruited in the ICU to complete a paper questionnaire to assess their
      willingness to use WCDs. The Theory of Planned Behaviour was used to assess
      attitudes, subjective norms, perceived control, and behavioral intent. Responses
      included Likert scale scores and open-ended questions. Data were collected before
      and following the implementation of WCDs in ICU. The combined effects of
      attitudes, perceived control and subjective norms on behavioral intent were
      tested using the general linear model. The narrative data were analyzed using a
      thematic analysis approach. Attitudes and subjective norms were predictors of
      behavioral intent to use WCDs preimplementation but not postimplementation.
      Differences in the factors affecting intent to use WCDs between the ICU and the
      surgical unit may be related to the unique nature of the critical care
      environment, and to the lack of a comprehensive preimplementation strategy. A
      study examining predictors of use on a general inpatient unit where a
      comprehensive implementation strategy was not employed would provide insight into
      whether these findings are related to the implementation strategy or the unique
      nature of the critical care environment. Improved understanding of the function
      and application of innovative technology at the point of care, and attention to
      the process of implementation may improve adoption of this potentially beneficial
      device. 

PMID- 24033885
TI  - Evaluation of micronuclear frequencies in both circulating lymphocytes and buccal
      epithelial cells of patients with oral lichen planus and oral lichenoid contact
      reactions.
AB  - OBJECTIVE: The aim of this study was to evaluate the frequency of micronuclei
      (MNs) in both circulating lymphocytes and buccal epithelial cells of patients
      with oral lichenoid contact reactions (OLCRs) or with oral lichen planus (OLP)
      and compare their MN scores with those of healthy controls (HCs). MATERIAL AND
      METHODS: The study group included 21 patients (mean age 51.3 +/- 12.4; 6 males,
      15 females) with OLCRs and 22 patients (mean age 47.6 +/- 14.4; 4 males, 18
      females) with OLP who were clinically diagnosed and histopathologically confirmed
      according to WHO diagnostic criteria (WHO Collaborating Centre for Oral
      Precancerous Lesions, 1978). All patients with OLCR demonstrated contact allergy
      to tested dental materials when evaluated by skin patch testing according to
      International Contact Dermatitis Research Group (ICDRG), while all OLP patients
      tested negative to patch testing. Seventeen individuals with no oral mucosal
      disorders (mean age 51.7 +/- 11.3; 8 males, 9 females) were recruited to
      constitute the healthy control group. [Correction added on 30 May 2014, after
      first online publication: the term, 'mean age' has been added to the text in
      parenthesis throughout the Material and Methods section.] Clinical features
      including type of OLP, location, disease severity, presence of skin lesions,
      presence of systemic disease including any allergies and dental (periodontal)
      status were recorded. MN analyses were performed on peripheral blood lymphocytes
      and on smears of buccal epithelial cells of all three study groups. RESULTS: Most
      OLP and OLCR lesions were of reticular type (83%), and OLP lesions were
      distributed bilaterally on the buccal mucosa (90.5%). The medians of MN
      frequencies in buccal epithelial cells in OLP and OLCR groups were significantly
      higher when compared with HC group (P < 0.001). [Correction added on 30 May 2014,
      after first online publication: in the results, 2nd sentence, the word
      'lymphocytes' has been removed.] There was no significant difference between OLP
      group (14.5 range 3-95) and OLCR group (16.0 range 3-93) in terms of median MN
      frequencies in buccal epithelial cells (P = 0.724) nor in peripheral lymphocytes
      between OLP group (2.0 range 0-7) and OLCR group (1.0 range 0-6) (P = 0.92).
      [Correction added on 30 May 2014, after first online publication: (P = 0.92) was
      wrongly placed after 'peripheral lymphocytes' and has now been shifted to the end
      of the last sentence.] CONCLUSIONS: Micronuclei scores do not distinguish OLP
      from OLCR when using buccal smears. OLP and OLCR both demonstrated significantly
      higher MN frequencies in buccal cells, compared with healthy controls. MN
      assessment in both buccal epithelial cells and circulating lymphocytes may serve
      as a potential biomarker tool for evaluating any cancer risk in OLP and OLCR.
      [Correction added on 30 May 2014, after first online publication: the first and
      second sentences in the conclusions have been slightly changed.].

PMID- 24033886
TI  - Perceptions of living with a device-based treatment: an account of patients
      treated with deep brain stimulation for Parkinson's disease.
AB  - OBJECTIVES: Deep brain stimulation (DBS) is an established treatment for
      Parkinson's disease. Little is known about patients' own perceptions of living
      with the implanted hardware. We aimed to explore patients' own perceptions of
      living with an implanted device. MATERIALS AND METHODS: Semistructured interviews
      with open-ended questions were conducted with 42 patients (11 women) who had been
      on DBS for a mean of three years. The questions focused on patients' experiences
      of living with and managing the DBS device. The interviews were transcribed
      verbatim and analyzed according to the difference and similarity technique in
      grounded theory. RESULTS: From the patients' narratives concerning living with
      and managing the DBS device, the following four categories emerged: 1) The device
      not a big issue: although the hardware was felt inside the body and also visible
      from outside, the device as such was not a big issue. 2) Necessary carefulness:
      Patients expressed the need to be careful when performing certain daily
      activities in order not to dislocate or harm the device. 3) Continuous need for
      professional support: Most patients relied solely on professionals for fine
      tuning the stimulation rather than using their handheld controller, even if this
      entailed numerous visits to a remote hospital. 4) Balancing symptom relief and
      side-effects: Patients expressed difficulties in finding the optimal match
      between decrease of symptoms and stimulation-induced side-effects. CONCLUSIONS:
      The in-depth interviews of patients on chronic DBS about their perceptions of
      living with an implanted device provided useful insights that would be difficult
      to capture by quantitative evaluations.

PMID- 24033887
TI  - Lobular carcinoma of male breast diagnosed on fine needle aspiration cytology--a
      case report.

PMID- 24033889
TI  - Local excision of rectal cancer followed by radical surgery because of poor
      prognostic features does not compromise the long term oncologic outcome.
AB  - AIM: The outcome of patients undergoing full-thickness local excision (LE) of
      rectal cancers may be compromised if poor prognostic features are found in the LE
      specimen. Our aim was to evaluate the long-term results of radical surgery
      performed after LE because poor prognostic factors are identified. METHOD:
      Patients with biopsy-proven rectal cancer who had undergone full-thickness LE
      followed by radical surgery because of a positive margin, T stage >=3,
      lymphovascular invasion, poor differentiation or mucinous histology were
      identified from a prospective database. Their records were retrospectively
      reviewed and follow up was updated. RESULTS: Between 1995 and 2003, 17 patients
      underwent LE followed by radical surgery because of poor prognostic features.
      Combined chemotherapy and radiotherapy was given to 11 (65%) patients before
      radical surgery. Patients underwent radical surgery after a median of 14 (range:
      0-40) weeks from LE. Nine underwent a low anterior resection and eight an
      abdominoperineal resection. At the time of radical surgery, residual disease was
      found in six (35%) patients (in lymph nodes in three; intramural in two; and both
      lymph nodes and intramural in one). Four of the patients with residual disease
      had undergone neoadjuvant therapy before radical surgery. The mean follow up was
      110 (95% CI: 92-129) months. Recurrence-free survival at 10 years was 88%. There
      was no case of local recurrence, and two patients died of metastatic disease.
      CONCLUSION: In this series patients who underwent early radical surgery because
      of poor prognostic features found at LE had good overall and cancer-specific long
      term survival. Even after neoadjuvant therapy, more than a third of patients had
      residual disease at the time of radical surgery. We therefore recommend radical
      surgery with neoadjuvant therapy when poor prognostic features are found at LE.

PMID- 24033888
TI  - Three-dimensional evaluation of upper airway in patients with different
      anteroposterior skeletal patterns.
AB  - OBJECTIVES: To investigate variability in the upper airway of subjects with
      different anteroposterior skeletal patterns by evaluating the volume and the most
      constricted cross-sectional area of the pharyngeal airway and defining
      correlations between the different variables. MATERIAL AND METHODS: The study
      sample consisted of 60 patients (29 boys, 31 girls) divided into three groups:
      Class I (1 <= ANB <= 3), Class II (ANB>3), and Class III (ANB<1), to evaluate how
      the jaw relationship affects the airway volume and the most constricted cross
      sectional area (Min-CSA). Differences between groups were determined using the
      Tukey-Kramer test. Correlations between variables were tested using Pearson's
      correlation coefficient. RESULTS: The volume and the Min-CSA of the pharyngeal
      airway (PA) were significantly related to anteroposterior skeletal patterns (p <
      0.05). The nasopharyngeal airway (NA) volume of Class I and Class III subjects
      was significantly larger than that of Class II subjects (p < 0.05). The Min-CSA
      and the length of PA were significantly related to the volume of PA (p < 0.05).
      The site and the size of the Min-CSA varied among the three groups. CONCLUSIONS:
      The volume and the most constricted cross-sectional area of the airway varied
      with different anteroposterior skeletal patterns. The NA volume of Class I and
      Class III subjects was significantly larger than that of patients with a Class II
      skeletal pattern.

PMID- 24033890
TI  - Precursor-derived versus de-novo carcinogenesis depends on lineage-specific mucin
      phenotypes of intramucosal gland-forming gastric neoplasms.
AB  - AIMS: To clarify the lineage-specific carcinogenesis of gland-forming gastric
      neoplasms, by characterizing mucin phenotypes and proliferation patterns
      immunohistochemically using monoclonal antibodies against MUC2, MUC5AC, MUC6,
      CD10 and Ki67. METHODS AND RESULTS: We analysed 49 gland-forming intramucosal
      neoplasms, including 15 non-invasive low-grade neoplasms (group A), 10 non
      invasive high-grade neoplasms (group B) and 24 intramucosal adenocarcinomas
      (group C). The mode of gland-forming gastric carcinoma development was different
      between the intestinal and gastric lineages. The pure intestinal-type accounted
      for 93% of group A, 50% of group B and 4.2% of group C tumours. A zonal pattern
      of cell proliferation was well retained in group A tumours and was lost size
      dependently in group B tumours. These findings suggest that non-invasive low
      grade neoplasms of the intestinal lineage progress to non-invasive high-grade
      neoplasms, but rarely to intramucosal adenocarcinomas. In tumours of the gastric
      lineage, which exhibited pure gastric or mixed phenotypes, the polarity of cell
      proliferation and differentiation was well retained in small (?5 mm) tumours but
      was lost in larger tumours in groups B and C. CONCLUSIONS: Intramucosal
      adenocarcinomas of the gastric lineage may often arise de novo, develop in the
      proper gastric mucosa, and are partially derived from non-invasive high-grade
      neoplasms.

PMID- 24033891
TI  - Are salmeterol's beneficial effects on corticosteroid action in the airways
      executed at the epithelial barrier?

PMID- 24033892
TI  - Histopathological characteristics of hypervascular cholangiocellular carcinoma as
      an early stage of cholangiocellular carcinoma.
AB  - AIM: Prognosis of hypervascular cholangiocellular carcinoma (h-CCC) is reportedly
      better than that of ordinary hypovascular CCC (o-CCC). The aim of this study is
      to clarify the histopathological characteristics of h-CCC. METHODS: On the basis
      of the findings in the arterial phase of contrast-enhanced computed tomography,
      16 cases of mass-forming-type CCC were divided into two groups (h-CCC, n = 8; o
      CCC, n = 8). Areas of high (Area H-a) and low (Area H-b) attenuation in h-CCC
      cases and areas of low attenuation in o-CCC cases (Area O) were delineated. These
      areas were then evaluated histopathologically to determine the proportion of
      tumor cells, fibrous stroma, arterial vessel density, and immunohistochemical
      expression of Vascular endothelial growth factor; angiopoietin-2; cytokeratin 7,
      CK19, SOX9 and SOX17 genes; epithelial cell adhesion molecule; and the Bmi-1, Ki
      67, epithelial membrane antigen and polyclonal carcinoembryonic antigen. RESULTS:
      The areal ratio of tumor cells decreased and that of fibrous stroma increased in
      the following order: Area H-a, Area H-b and Area O. Values for AVD and neural
      cell adhesion molecule positivity rate were significantly higher in Area H-a than
      in Areas H-b or O. Expressions of vascular endothelial growth factor and
      angiopoietin-2 were significantly higher in Areas H-a and H-b than in Area O. The
      Ki-67 labeling index increased in the following order: Area H-a, Area H-b and
      Area O. CONCLUSION: A high areal ratio of tumor cells and AVD as well as a high
      expression of stem cells and angiogenic markers were observed in cases of h-CCC,
      whereas the areal ratio of fibrous stroma and malignant potential were low. These
      results suggest that h-CCC may represent the early stage of CCC.

PMID- 24033893
TI  - Congenital Reproductive Abnormalities.
AB  - Congenital defects of the reproductive system are associated with a number of
      adverse health consequences. The pathophysiology of these defects is thought to
      be mullerian abnormalities, but they can also be attributed to failure of cells
      to degenerate appropriately during embryogenesis. The management of these
      congenital defects is dependent on the type of defect present and the severity of
      presentation. Women with congenital defects of the reproductive system have
      physical as well as psychosocial issues that must be addressed, and the condition
      frequently creates medical challenges for health care providers. 

PMID- 24033894
TI  - Conclusions from the HIV in Europe Copenhagen 2012 Conference and ways forward:
      working together for optimal HIV testing and earlier care.
AB  - The objective of this article is to set the scene for this supplement by
      presenting and discussing the overall outcomes of the HIV in Europe Copenhagen
      2012 Conference and how the HIV in Europe initiative intends to further address
      challenges and themes raised during the conference. 

PMID- 24033895
TI  - Routine HIV testing in the emergency department: tough lessons in sustainability.
AB  - OBJECTIVES: Routine HIV testing in nonspecialist settings has been shown to be
      acceptable to patients and staff in pilot studies. The question of how to embed
      routine HIV testing, and make it sustainable, remains to be answered. METHODS: We
      established a service of routine HIV testing in an emergency department (ED) in
      London, delivered by ED staff as part of routine clinical care. All patients aged
      16 to 65 years were offered an HIV test (latterly the upper age limit was
      removed). Meetings were held weekly and two outcome measures examined: test offer
      rate (coverage) and test uptake. Sustainability methodology (process mapping;
      plan-do-study-act (PDSA) cycles) was applied to maximize these outcome measures.
      RESULTS: Over 30 months, 44,582 eligible patients attended the ED. The mean
      proportion offered an HIV test was 14%, varying from 6% to 54% per month over the
      testing period. The mean proportion accepting a test was 63% (range 33-100%). A
      total of 4327 HIV tests have been performed. Thirteen patients have been
      diagnosed with HIV infection (0.30%). PDSA cycles having the most positive and
      sustained effects on the outcome measures include the expansion to offer blood
      based HIV tests in addition to the original oral fluid tests, and the engagement
      of ED nursing staff in the programme. CONCLUSIONS: HIV testing can be delivered
      in the ED, but constant innovation and attention have been required to maintain
      it over 30 months. Patient uptake remains high, suggesting acceptability, but
      time will be required before true embedding in routine clinical practice is
      achieved.

PMID- 24033896
TI  - Acceptability, feasibility and costs of universal offer of rapid point of care
      testing for HIV in an acute admissions unit: results of the RAPID project.
AB  - OBJECTIVES: UK guidance recommends that acute medical admissions are offered an
      HIV test. Our aim was to determine whether a dedicated staff member using a
      multimedia tool, a model found effective in the USA, is an acceptable, feasible,
      and cost-effective model when translated to a UK setting. METHODS: Over 4 months
      in 2010, a health advisor (HA) approached 19-65-year-olds at a central London
      acute medical admissions unit and offered a rapid HIV point of care test (POCT)
      with the aid of an educational video. Feasibility and acceptability were assessed
      through surveys and uptake rates. Costs per case of HIV infection identified were
      established. RESULTS: Of the 606 eligible people admitted during the pilot, 324
      (53.5%) could not be approached or were individuals for whom testing was deemed
      inappropriate. In total, 23.0% of eligible admissions had an HIV POCT. Of the
      patients who watched the video and had not recently been tested for HIV, 93.6%
      (131 of 140) agreed to an HIV test; four further patients had an HIV test but did
      not watch the video. Three tests (2.2%; three of 135) were reactive and all were
      confirmed HIV positive on laboratory testing. HIV testing in this setting was
      felt to be appropriate by 97.5% of individuals. The cost per patient was L21, and
      the cost per case of HIV identified was L1083. CONCLUSIONS: Universal POCT HIV
      testing in an acute medical setting, facilitated by an educational video and
      dedicated staff, appears acceptable, feasible, effective, and low cost. These
      findings support the recommendation of HIV testing for all medical admissions in
      high-prevalence settings, although with this model a significant proportion
      remained untested.

PMID- 24033897
TI  - HIV testing among Portuguese men who have sex with men--results from the European
      MSM Internet Survey (EMIS).
AB  - OBJECTIVES: To describe HIV testing behaviour and context of MSM in Portugal
      participating in the European MSM Internet Survey (EMIS). METHODS: Data for the
      Portuguese sample were extracted and those for 5187 participants were analysed.
      Multivariate logistic regression models were fitted to quantify the association
      between participants' characteristics and HIV testing behaviour and context.
      RESULTS: Seventy-two percent of the participants had ever been tested for HIV and
      among those ever tested, 11% were diagnosed with HIV. Primary care was the most
      common testing setting for HIV-negative men (37%). Compared to those never
      tested, men who had ever taken an HIV test had higher educational level (aOR
      1.89, 95% CI 1.67-2.14) and identified themselves as gay/homosexual more
      frequently (aOR 1.94 , 95% CI 1.70-2.20). HIV testing odds significantly
      increased with the number of sexual partners in the previous 12 months. Those who
      reported unprotected anal intercourse (UAI) with a partner of unknown or
      serodiscordant HIV status in the previous 12 months were less likely to report an
      HIV test (aOR 0.38, 95% CI 0.33-0.44). Among those never tested or who tested
      negative, 41% and 22% reported UAI with a partner of unknown or serodiscordant
      status in the previous 12 months, respectively. Among men with diagnosed HIV, 72%
      were currently on antiretroviral therapy and 58% reported an undetectable viral
      load. More than one third (38%) of those who had detectable or
      unknown/undisclosed viral load reported at least one episode of UAI with a
      partner of unknown or serodiscordant HIV status in the last 12 months.
      CONCLUSIONS: Actual interventions should focus on: improving testing uptake and
      counselling; increasing treatment coverage; achieving and maintaining an
      undetectable viral load; and intensifying prevention efforts focused on
      consistent condom use.

PMID- 24033898
TI  - Quality of HIV care in the United Kingdom: key indicators for the first 12 months
      from HIV diagnosis.
AB  - OBJECTIVES: Prompt HIV diagnosis and treatment are associated with increased
      longevity and reduced transmission. The aim of the study was to examine late
      diagnoses and to assess the quality of care following diagnosis. METHODS:
      National surveillance and cohort data were used to examine late HIV diagnoses and
      to assess the quality of care received in the 12 months following HIV diagnosis.
      RESULTS: In 2011, 79% (4910/6219) of persons (15 years and over) diagnosed with
      HIV infection had CD4 counts reported within 3 months; of these, 49% were
      diagnosed late (CD4 count < 350 cells/MUL). Adults aged 50 years and over were
      more likely to be diagnosed late (67%) compared with those aged 15-24 years
      (31%). Sixty-four per cent of heterosexual men were diagnosed late compared with
      46% of women and 36% of men who have sex with men (MSM) (P < 0.01). The
      percentage of late diagnoses was highest among black African adults (66%)
      compared with other ethnicities; 96% of black African adults diagnosed late were
      born abroad. Overall, 88% and 97% of patients were linked to care within 1 and 3
      months of diagnosis, respectively, with little variation by demographics and
      exposure category. The crude 1-year mortality rate was 31.6 per 1000 persons
      diagnosed in 2010. It was highest among adults diagnosed late (40.3/1000 versus
      5.2/1000 for prompt diagnoses) and particularly among those aged 50 years and
      over. Excluding deaths, 85% of the 5833 diagnosed in 2010 were retained in care
      in 2011; 92% of the 2264 adults diagnosed late in 2010 received antiretroviral
      therapy by the end of 2011. CONCLUSIONS: The National Health Service provides
      high-quality care to persons newly diagnosed with HIV infection in the UK, with
      no evidence of health inequalities. Despite excellent care, half of adults are
      diagnosed late according to the threshold at which national guidelines recommend
      treatment should begin. Such patients have an 8-fold increased risk of 1-year
      mortality compared with those diagnosed promptly. Reducing late diagnosis of HIV
      infection remains a public health priority in the UK.

PMID- 24033899
TI  - BCN Checkpoint, a community-based centre for men who have sex with men in
      Barcelona, Catalonia, Spain, shows high efficiency in HIV detection and linkage
      to care.
AB  - OBJECTIVES: We assessed the efficiency of BCN Checkpoint in detecting new cases
      of HIV infection and efficiently linking newly diagnosed individuals to care.
      METHODS: This study analysed during 2007-2012 the number of tests performed and
      the number of persons tested in BCN Checkpoint, the HIV prevalence, global and in
      first visits, the capacity of HIV detection compared to the reported cases in MSM
      in Catalonia, and the linkage to care rate. RESULTS: During the six years a total
      of 17.319 tests were performed and 618 HIV-positive cases were detected. Median
      prevalence of clients who visited the centre for the first time was 5.4% (4.1
      5.8). BCN Checkpoint detected 36.3% (35.0-40.4) of all reported cases in MSM
      during 2009-2011. Linkage to care was achieved directly in 90.5% of the cases and
      only 2.4% of cases were lost to follow-up. CONCLUSIONS: A community-based centre,
      addressed to a key population at risk, can be less effort consuming (time and
      funding) and show high efficiency in HIV detection and linkage to care.

PMID- 24033900
TI  - HIV testing uptake among female sex workers and men who have sex with men in
      Tbilisi, Georgia.
AB  - OBJECTIVES: The aim of the study was to investigate HIV testing practice among
      female sex workers (FSWs) and men who have sex with men (MSM) in Tbilisi, Georgia
      and to identify determinants of never testing behaviour among MSM. METHODS: Data
      obtained in two rounds of bio-behavioural surveys among FSWs (2006 and 2009) and
      MSM (2007 and 2010) were analysed. Determinants of never testing behaviour among
      MSM were investigated among 278 respondents recruited in 2010 through respondent
      driven sampling. RESULTS: Knowledge about the availability of HIV testing and
      never testing behaviour did not show changes among FSWs and MSM. Every third FSW
      and every second MSM had never been tested for HIV according to the latest
      surveys in 2010. In bivariate analysis among MSM, consistent condom use during
      anal intercourse with a male partner in the last year, awareness of HIV testing
      locations and preventive programme coverage were negatively associated with never
      testing behaviour, while those who considered themselves at no risk of HIV
      transmission were more likely to have never been tested. In multivariate
      analysis, lower odds of never testing for HIV remained for those who were aware
      of HIV testing locations [adjusted odds ratio (AOR) 0.12; 95% confidence interval
      (CI) 0.04-0.32] and who reported being covered by HIV prevention programmes (AOR
      0.26; 95% CI 0.12-0.56). CONCLUSIONS: In view of the concentrated HIV epidemic
      among MSM in Georgia and the low rate of HIV testing uptake, interventions in
      this key population should take into consideration the factors associated with
      testing behaviour. The barriers to HIV testing and counselling uptake should be
      further investigated.

PMID- 24033901
TI  - Comparison of two HIV testing strategies in primary care centres: indicator
      condition-guided testing vs. testing of those with non-indicator conditions.
AB  - OBJECTIVES: The aim of the study was to compare prospectively indicator-condition
      (IC)-guided testing versus testing of those with non-indicator conditions (NICs)
      in four primary care centres (PCCs) in Barcelona, Spain. METHODS: From October
      2009 to February 2011, patients aged from 18 to 65 years old who attended a PCC
      for a new herpes zoster infection, seborrhoeic eczema, mononucleosis syndrome or
      leucopenia/thrombopenia were included in the IC group, and one in every 10
      randomly selected patients consulting for other reasons were included in the NIC
      group. A proportion of patients in each group were offered an HIV test; those who
      agreed to be tested were given a rapid finger-stick HIV test (?6 per test).
      Epidemiological and clinical data were collected and analysed. RESULTS: During
      the study period, 775 patients attended with one of the four selected ICs, while
      66,043 patients presented with an NIC. HIV screening was offered to 89 patients
      with ICs (offer rate 11.5%), of whom 85 agreed to and completed testing (94.4 and
      100% acceptance and completion rates, respectively). In the NIC group, an HIV
      test was offered to 344 persons (offer rate 5.2%), of whom 313 accepted (90.9%)
      and 304 completed (97.1%) testing. HIV tests were positive in four persons
      [prevalence 4.7%; 95% confidence interval (CI) 1.3-11.6%] in the IC group and in
      one person in the NIC group (prevalence 0.3%; 95% CI 0.01-1.82%; P < 0.009). If
      every eligible person had taken an HIV test, we would have spent ?4650 in the IC
      group and ?396,258 in the NIC group, and an estimated 36 (95% CI 25-49) and 198
      persons (95% CI 171-227), respectively, would have been diagnosed with HIV
      infection. The estimated cost per new HIV diagnosis would have been ?129 (95% CI
      ?107-153) in the IC group and ?2001 (95% CI ?1913-2088) in the NIC group.
      CONCLUSIONS: Although the number of patients included in the study was small and
      the results should be treated with caution, IC-guided HIV testing, based on four
      selected ICs, in PCCs seems to be a more feasible and less expensive strategy to
      improve diagnosis of HIV infection in Spain than a nontargeted HIV testing
      strategy.

PMID- 24033902
TI  - Association of injecting drug use and late enrolment in HIV medical care in
      Odessa Region, Ukraine.
AB  - OBJECTIVES: Late entry of HIV-positive persons into specialized care is a
      significant challenge to limiting the spread of the HIV epidemic. In 2008-2010,
      only 54% of 108,116 persons who tested HIV positive enrolled in care at AIDS
      Centers in Ukraine, and almost half of new AIDS cases are found in patients with
      first-time HIV diagnoses. We aimed to identify factors associated with delayed
      enrolment in HIV care in Odessa Region, Ukraine. METHODS: We conducted a
      retrospective data analysis of patients who enrolled in HIV care in 1995-2010,
      comparing patients on the basis of the reported route of HIV transmission
      (injecting drug use or sexual transmission). The nonparametric Mann-Whitney U
      test was used to compare the groups. RESULTS: During the period analysed, the
      delay in enrolment in HIV care among people who inject drugs (PWID) in Odessa
      Region was longer than that among people infected via sexual transmission. The
      mean delay in enrolment in care among PWID increased over time for men and women;
      their mean age at the time of enrolment also gradually increased. Urban residents
      accounted for the majority of HIV cases, with some growth in the proportion of
      rural residents. CONCLUSIONS: People who acquired HIV via injecting drug use
      showed later enrolment in HIV care compared with people infected via sexual
      transmission. There is an urgent need to improve HIV counselling and referral
      services, taking into account differences in the behaviour of drug-using and non
      drug-using populations.

PMID- 24033903
TI  - HIV testing of patients diagnosed with tuberculosis increased in Denmark during
      the period from 2007 to 2009.
AB  - We examined the trends of HIV testing among patients notified with TB in Denmark
      during a 3-year period from 2007 to 2009. We were able to obtain HIV testing
      status for 96%. There was a significant increase of patients examined for HIV
      infection during the 3-year period. HIV prevalence among HIV-tested TB patients
      in Denmark is much higher than in the average population. It seems there is an
      increasing awareness in Denmark towards testing TB cases for HIV co-infection. 

PMID- 24033905
TI  - Automatic oral fluid-based HIV testing in HIV screening programmes: automatic for
      the people.
AB  - OBJECTIVES: UK guidelines recommend routine HIV testing in general clinical
      settings when the local HIV prevalence is > 0.2%. During pilot programmes
      evaluating the guidelines, we used laboratory-based testing of oral fluid from
      patients accepting tests. Samples (n = 3721) were tested manually using the Bio
      Rad Genscreen Ultra HIV Ag-Ab test (Bio-Rad Laboratories Ltd, Hemel Hempstead,
      UK). This was a methodologically robust method, but handling of samples was
      labour intensive. We performed a validation study to ascertain whether automation
      of oral fluid HIV testing using the fourth-generation HIV test on the Abbott
      Architect (Abbott Diagnostics, Maidenhead, UK) platform was possible. METHODS:
      Oral fluid was collected from 143 patients (56 known HIV-positive volunteers and
      87 others having contemporaneous HIV serological tests) using the Oracol+ device
      (Malvern Medicals, Worcester, UK). Samples were tested concurrently: manually
      using the Genscreen Ultra test and automatically on the Abbott Architect.
      RESULTS: For oral fluid, the level of agreement of results between the platforms
      was 100%. All results agreed with HIV serology. The use of the Oracol+ device
      produced high-quality samples. Subsequent field use of the test has shown a
      specificity of 99.97% after nearly 3000 tests. CONCLUSIONS: Laboratory-based HIV
      testing of oral fluid requires less training of local staff, with fewer demands
      on clinical time and space than near-patient testing. It is acceptable to
      patients. The validation exercise and subsequent clinical experience support
      automation, with test performance preserved. Automation reduces laboratory
      workload and speeds up the release of results. Automated oral fluid testing is
      thus a viable option for large-scale HIV screening programmes.

PMID- 24033904
TI  - Who are the men who have sex with men in Spain that have never been tested for
      HIV?
AB  - OBJECTIVES: The aims of the study were to describe the sociodemographic profile
      of men who have sex with men (MSM) who have never been tested for HIV and to
      analyse factors associated with never having been tested. METHODS: The European
      MSM Internet Survey (EMIS) was implemented in 2010 in 38 European countries on
      websites for MSM and collected data on sociodemographics, sexual behaviour, and
      other sexual health variables. A logistic regression analysis was conducted to
      assess variables associated with never having been tested for HIV. RESULTS: Of
      the 13,111 respondents living in Spain, 26% had never been tested for HIV. Those
      who had never been tested were significantly more likely to live in a settlement
      with fewer than 100,000 inhabitants, be younger than 25 years old, have a lower
      education level, be a student, and identify themselves as bisexual. In the
      multivariate analysis, to have never been tested for HIV was associated with
      being born in Spain [odds ratio (OR) 1.35; 95% confidence interval (CI) 1.192
      1.539], living outside large settlements (OR 1.37; 95% CI 1.216-1.534), being
      younger than 25 years old (OR 2.94; 95% CI 2.510-3.441), being out to no one or
      only a few people (OR 2.16; 95% CI 1.938-2.399), having had no nonsteady partners
      in the last 12 months (OR 1.26; 95% CI 1.109-1.422), and being not at all
      confident to access HIV testing (OR 3.66; 95% CI 2.676-5.003), among others
      factors. CONCLUSIONS: The profile of the MSM who had never been tested for HIV
      indicates that most of them were men who were hard to reach (young, bisexual men,
      in the closet). Interventions should aim to improve access to and the convenience
      of testing.

PMID- 24033906
TI  - Attitudes to rapid HIV testing among Spanish General Practitioners.
AB  - OBJECTIVES: The objectives of this study were to investigate the acceptability of
      rapid HIV testing among general practitioners in Spain and to identify perceived
      barriers and needs in order to implement rapid testing in primary care settings.
      METHODS: An anonymous questionnaire was distributed online to all members of the
      two largest Spanish scientific medical societies for family and community
      medicine. The study took place between 15th June and 31st October 2010. RESULTS:
      Completed questionnaires were returned by 1308 participants. The majority (90.8%)
      of respondents were General Practitioners (GP). Among all respondents, 70.4% were
      aware of the existence of rapid tests for the diagnosis of HIV but they did not
      know how to use them. Nearly 80% of participants would be willing to offer rapid
      HIV testing in their practices and 74.7% would be confident of the results
      obtained by these tests. The barriers most commonly identified by respondents
      were a lack of time and a need for training, both in the use of rapid tests
      (44.3% and 56.4%, respectively) and required pre- and post-test counselling
      (59.2% and 34.5%, respectively). CONCLUSIONS: This study reveals a high level of
      acceptance and willingness on the part of GPs to offer rapid HIV testing in their
      practices. Nevertheless, the implementation of rapid HIV testing in primary care
      will not be possible without moving from comprehensive pre-test counselling
      towards brief pre-test information and improving training in the use of rapid
      tests.

PMID- 24033907
TI  - Feasibility and acceptability of HIV screening through the use of rapid tests by
      general practitioners in a Brussels area with a substantial African community.
AB  - OBJECTIVES: To assess:1) if HIV screening with rapid tests in neighbourhoods with
      a substantial African community is feasible and acceptable among GPs and
      patients; 2) HIV seroprevalence. METHODS: Multicenter prospective study with 10
      trained physicians. Use of HIV standard test and INSTI Ultrarapid test. INCLUSION
      CRITERIA: MSM, sex worker, multiple sexual partners, having returned or coming
      from a country with high HIV prevalence, IVDU, Indicator conditions as defined by
      HIV Indicator Diseases across Europe Study, having an AIDS-defining illness,
      having had a recent pregnancy or abortion; or presenting other risks. RESULTS:
      From August 2010 to August 2011, 10 trained GPs offered an HIV test to 224
      patients: 51% ?, 48% ?, 43% Caucasians, 45% Africans. INCLUSION CRITERIA: 32%
      "high risk group", 9% returning from an endemic country, 29% with an indicator
      condition; 12 patients (6%) refused the standard test. The INSTI was offered to
      217(97%), 197 performed with 2 reactive rapid tests confirmed. The seroprevalence
      according to ethnic origin was 0% among Caucasians and 2.2% among Africans and
      was 1.5% among patients with an indicator condition. 1087 consecutive
      consultations of the same GPs were recorded: 42% patients had >= 1 inclusion
      criteria among which 41% of offered tests, that is to say 59% of "missed
      opportunities". The reasons for not offering the test as recorded for 55% of
      patients:"not indicated" 44.5%, "no time" 33%, "impossible to propose" 15%, test
      completed previously 11%, known HIV-positive 4%. CONCLUSIONS: Standard and rapid
      tests are well received by patients but were usually not offered by doctors who
      have been trained.

PMID- 24033908
TI  - Infant dental enucleation in an East African population in Sweden: a cross
      sectional study on dental records.
AB  - AIM: To examine the prevalence of infant dental enucleation (IDE) of primary
      canines, an East African traditional remedial procedure, in a multiethnic
      population of children in Sweden. DESIGN: A cross-sectional study was conducted
      of dental records of 1133 patients (mean age 4.6 years, SD +/- 1.4) attending one
      public dental service clinic in Sweden. The clinic was located in an area with a
      large multiethnic community. All were born within the years 2002-2006 and had
      received a check-up in one of the years 2007-2009. A registry was made of missing
      primary canines where no reason could be found. In documented cases, information
      about ethnic origin was extracted. Statistical grouping was made according to
      known East African ethnicities. RESULTS: At least 36 ethnicities were recorded.
      Twenty-four (2.1%) patients were missing one or more canines according to the
      criteria for IDE. Significant difference was seen when comparison was made
      between patients of known East African ethnicities, of whom 20.8% (21/101)
      manifested findings consistent with the criteria, and the rest of the population
      (3/1032; P < 0.001). CONCLUSIONS: Prevalence of cases suggestive of IDE among
      patients of East African origin points to a need for increased awareness within
      dental and healthcare communities.

PMID- 24033909
TI  - Therapeutic strategy for patients with bleeding rectal varices complicating liver
      cirrhosis.
AB  - AIM: Although rupture of rectal varices is rarely encountered, it may provoke
      massive and fatal hemorrhage in patients with liver cirrhosis. We examined the
      clinical features of patients showing bleeding from rectal varices to establish a
      suitable therapeutic strategy for the lesions. METHODS: Twelve cirrhotic patients
      with bleeding rectal varices were enrolled. Surgical suture, endoscopic variceal
      ligation (EVL) or balloon tamponade was performed to achieve the initial
      hemostasis. Then, the feeding and drainage vessels of the varices were evaluated
      by computed tomography, and additional procedures were undertaken: EVL was
      performed when the sizes of the varices and feeding vessels were small. In
      contrast, in patients with varices of large sizes, balloon-occluded retrograde
      transvenous obliteration (B-RTO) was performed when single or two drainage
      vessels were identified, while endoscopic injection sclerotherapy (EIS) using
      ethanolamine oleate was carried out for varices with three or more drainage
      vessels. RESULTS: The Child-Pugh class was grade A in four, B in six and C in two
      patients. Eleven patients had received previous therapy for esophageal varices.
      Initial hemostasis was achieved by surgical suture in three patients, EVL in one
      patient and balloon tamponade in two patients. EVL, EIS and B-RTO were carried
      out as additional procedures in seven, three and one patient, respectively.
      Rebleeding from the rectal varices occurred in only one patient who underwent EVL
      as an additional procedure. CONCLUSION: Bleeding from rectal varices was
      controlled satisfactorily by the therapeutic strategy of selecting EVL, EIS or B
      RTO as an additional therapy according to the size and hemodynamics of the
      varices.

PMID- 24033910
TI  - A multicenter, randomized, double-blinded, placebo-controlled phase III study of
      Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage
      (CLEAR III).
AB  - BACKGROUND: In adults, intraventricular thrombolytic therapy with recombinant
      tissue plasminogen activator (rtPA) facilitates resolution of intraventricular
      haemorrhage (IVH), reduces intracranial pressure, decreases duration of
      cerebrospinal fluid diversion, and may ameliorate direct neural injury. We
      hypothesize that patients with small parenchymal haematoma volumes (<30 cc) and
      relatively large IVH causing acute obstructive hydrocephalus would have improved
      clinical outcomes when given injections of low-dose rtPA to accelerate lysis and
      evacuation of IVH compared with placebo. METHODS: The Clot Lysis Evaluation of
      Accelerated Resolution of Intraventricular Hemorrhage III trial is an
      investigator-initiated, phase III, randomized, multicenter, double-blind, placebo
      controlled study comparing the use of external ventricular drainage (EVD)
      combined with intraventricular injection of rtPA to EVD plus intraventricular
      injection of normal saline (placebo) for the treatment of IVH. Patients with
      known symptom onset within 24 h of the computed tomography scan confirmed IVH and
      third or fourth ventricle obstruction, with or without supratentorial
      intracerebral haemorrhage volume <30 cc, who require EVD are screened with a
      computed tomography scan at least six hours after EVD placement and, if
      necessary, at consecutive 12-h intervals until stabilization of any intracranial
      bleeding has been established. Patients who meet clinical and imaging criteria
      (no ongoing coagulopathy and no suspicion of aneurysm, arteriovenous
      malformation, or any other vascular anomaly) will be randomized to either
      intraventricular rtPA or placebo. RESULTS: The primary outcome measure is
      dichotomized modified Rankin Scale 0-3 vs. 4-6 at 180 days. Clinical secondary
      outcomes include additional modified Rankin Scale dichotomizations at 180 days (0
      4 vs. 5-6), ordinal modified Rankin Scale (0-6), mortality and safety events at
      30 days, mortality at 180 days, functional status measures, type and intensity of
      intensive care unit management, rate and extent of ventricular blood clot
      removal, and quality of life measures.

PMID- 24033911
TI  - Chemical and ultrastructural studies of lignocellulose biodegradation during
      Agaricus bisporus cultivation.
AB  - During Agaricus bisporus cultivation, lignocellulose degradation is the result of
      the activity of both the mushroom and microbial communities developed during the
      composting. To investigate the lignocellulose degradation in detail from the
      beginning to the end of the process, the functional groups of cellulose,
      hemicellulose, and lignin have been studied with Fourier transform infrared
      spectroscopy and the morphological changes of lignocelluloses were elucidated
      with scanning electron microscopy. The aperture of lignin and cellulose increased
      to enable the mycelia of A. bisporus to penetrate into the medium and to degrade
      lignocelluloses in a more direct way. The chemical structure changes implied a
      preferential use of lignin that could make for better use of cellulose to boost
      growth of A. bisporus. Changes in chemical structure together with
      ultrastructural changes induced by the microbial flora during cultivation
      substrate production by the composting substrate are important in promoting the
      utilization of lignocelluloses by A. bisporus. 

PMID- 24033912
TI  - A resequencing program in India detects the rare JAK2 L579F mutation in patients
      suffering from polycythemia vera and negative for JAK2 V617F.

PMID- 24033913
TI  - Comparative genomics and transcriptomics analysis of experimentally evolved
      Escherichia coli MC1000 in complex environments.
AB  - It has recently become feasible to study the basis and nature of evolutionary
      changes in bacteria in an experimental setting using defined media. However,
      assessment of adaptive changes in complex environments has been scarce. In an
      effort to describe the responses in such environments, we unravel, in a
      comparative approach, the transcriptional and genetic profiles of 19 Escherichia
      coli strains that evolved in Luria Bertani medium under three different oxygen
      regimes over 1000 generations. A positive relationship between upregulation of
      gene expression and the number of mutations was observed, suggesting that a
      number of metabolic pathways were activated. Phenotypic polymorphisms were
      observed in parallel cultures, of which some were related with mutations at the
      regulatory level. Non-parallel responses were observed at the intrapopulational
      level, which is indicative of diversifying selection. Parallel responses
      encompassed transcriptome diversity, and their effects were directly affected by
      differing genomic backgrounds. A fluctuating selective force produced higher
      phenotypic diversity compared with constant forces. This study demonstrates how
      phenotypic innovations may depend on the relationship between genomic changes and
      local ecological conditions. Using both comparative genomics and transcriptomics
      approaches, the results help elucidating various adaptive responses in cultures
      in unexplored complex environments. 

PMID- 24033915
TI  - Unusual ectopic pregnancies: a retrospective analysis of 65 cases.
AB  - AIM: The aim of this study was to retrospectively investigate unusual ectopic
      pregnancies (EP) and compare them with fallopian ones. MATERIAL AND METHODS: A
      total of 1000 cases of ectopic pregnancies were analyzed, including 65 unusual
      cases. We discussed distribution, incidence, risk factors, examinations,
      treatments and prognoses. RESULTS: Ovarian pregnancy was associated with
      placement of intrauterine device and pelvic inflammatory diseases. Extratubal EP
      have a high rate of misdiagnosis and presented more serious manifestations. Some
      unusual EP could be diagnosed by ultrasonography. Ovarian pregnancy was usually
      manifested as positive culdocentesis. Most of the unusual EP underwent surgery,
      except some early cervical and corneal pregnancies. CONCLUSION: Although
      extratubal pregnancies are difficult to diagnose, some histories and auxiliary
      examinations could make diagnosis easier for clinical physicians. Surgery is
      still the most effective approach for treatment of unusual EP, while conservative
      treatment of mifepristone combined with methotrexate or curettage could be used
      for early diagnosis and treatment of cervical pregnancy.

PMID- 24033916
TI  - Physiological and biotechnological implications of transcript-level variation
      under abiotic stress.
AB  - The discovery of genes that can be used to increase plant tolerance to
      environmental stress has practical implications for agriculture, since knowledge
      at the molecular level can potentially be translated from model plants to crops
      or from tolerant to sensitive cultivars. For more than a decade, researchers have
      attempted to identify transcriptional and metabolic pathways involved in stress
      tolerance using functional genomics tools. In some cases, promising results were
      obtained when a clear causal link was found between transcripts and
      tolerance/sensitivity to stress. However, recent reports question the global
      translational power of functional genomics for biotechnological applications, as
      one of the main limitations seems to be the large variability in gene expression.
      Transcript-level variability under stress has not been considered of interest in
      the scientific literature because it is intuitively obvious, but most reports
      seem to naively overlook the consequences. Here, three case situations are
      reviewed (variability between genotypes, variability due to environmental
      interactions and variability between stressors) in support of the concept that
      inherent transcript-level variation in biological systems may limit our knowledge
      of environmental plant tolerance and of functional genomics in molecular stress
      physiology. 

PMID- 24033914
TI  - Insulin and IGF1 enhance IL-17-induced chemokine expression through a GSK3B
      dependent mechanism: a new target for melatonin's anti-inflammatory action.
AB  - Obesity is a chronic inflammation with increased serum levels of insulin, insulin
      like growth factor 1 (IGF1), and interleukin-17 (IL-17). The objective of this
      study was to test a hypothesis that insulin and IGF1 enhance IL-17-induced
      expression of inflammatory chemokines/cytokines through a glycogen synthase
      kinase 3beta (GSK3B)-dependent mechanism, which can be inhibited by melatonin. We
      found that insulin/IGF1 and lithium chloride enhanced IL-17-induced expression of
      C-X-C motif ligand 1 (Cxcl1) and C-C motif ligand 20 (Ccl20) in the Gsk3b(+/+) ,
      but not in Gsk3b(-/-) mouse embryonic fibroblast (MEF) cells. IL-17 induced
      higher levels of Cxcl1 and Ccl20 in the Gsk3b(-/-) MEF cells, compared with the
      Gsk3b(+/+) MEF cells. Insulin and IGF1 activated Akt to phosphorylate GSK3B at
      serine 9, thus inhibiting GSK3B activity. Melatonin inhibited Akt activation,
      thus decreasing P-GSK3B at serine 9 (i.e., increasing GSK3B activity) and
      subsequently inhibiting expression of Cxcl1 and Ccl20 that was induced either by
      IL-17 alone or by a combination of insulin and IL-17. Melatonin's inhibitory
      effects were only observed in the Gsk3b(+/+) , but in not Gsk3b(-/-) MEF cells.
      Melatonin also inhibited expression of Cxcl1, Ccl20, and Il-6 that was induced by
      a combination of insulin and IL-17 in the mouse prostatic tissues. Further,
      nighttime human blood, which contained high physiologic levels of melatonin,
      decreased expression of Cxcl1, Ccl20, and Il-6 in the PC3 human prostate cancer
      xenograft tumors. Our data support our hypothesis and suggest that melatonin may
      be used to dampen IL-17-mediated inflammation that is enhanced by the increased
      levels of insulin and IGF1 in obesity. 

PMID- 24033917
TI  - Hospital-acquired conditions after orthopedic surgery do not affect patient
      satisfaction scores.
AB  - INTRODUCTION: The purpose of this study was to determine whether development of a
      hospital-acquired condition (HAC) affected responses to Hospital Consumer
      Assessment of Healthcare Providers and Systems (HCAHPS) survey questions. HCAHPS
      is a national, standardized satisfaction survey. Patient responses form, in part,
      the basis for Medicare reimbursement to hospitals via the value-based purchasing
      system established by the Patient Protection and Affordable Care Act of 2010. We
      hypothesized that patients who developed an HAC would be less satisfied with
      their care. METHODS: We randomly distributed the HCAHPS survey, a validated,
      standardized measure of patient satisfaction, to 6,056 patients discharged from
      our institution for any orthopedic admission over a 2-year period. All patients
      who develop HACs are logged by our hospital quality assurance monitoring system.
      We reviewed the HCAHPS database, identified completed surveys associated with
      patients who had developed an HAC, and compared satisfaction scores between
      patients with HACs and patients without HACs. Survey scores were normalized to a
      100-point scale. Univariate analysis was performed for two global ratings, and
      six specific satisfaction categories. Subgroup analysis was performed for
      surgical site infections (SSIs) and venous thromboembolic disease (VTE). RESULTS:
      A total of 2,876 controls and 159 HAC cases were identified from completed
      surveys. The cases and controls were similar in terms of race, however, the HAC
      group contained significantly more women (p < .001). Patients in the HAC group
      also were, on average, significantly older, with a mean age of 66.84 versus 58.65
      (p < .001). There was no difference in satisfaction scores in patients' mean
      rating of communication by nurses (p = .81), communication by doctors (p = .31),
      communication about medications (p = .69), pain control (p = .66), the
      cleanliness of the hospital environment (p = .54), and the quietness of the
      hospital (p = .589). The mean normalized score for overall satisfaction was 93.99
      (out of 100) for controls and 94.84 for HAC cases (p = .61). The mean normalized
      score for overall willingness to recommend the hospital to others was 90.22 for
      controls and 90.65 for HAC cases (p = .77). There was no statistically
      significant difference in satisfaction for patients with SSI versus VTE versus
      all other HACs (p > .05). DISCUSSION: Performance on HCAHPS is an area that
      demands hospital attention both to provide patient-centered care and to maximize
      revenue. Development of an HAC was not associated with decreased satisfaction
      scores in a population of orthopedic surgery patients at a private, university
      affiliated specialty center. The lack of any statistically significant difference
      in patient satisfaction may be attributable to patient satisfaction with care in
      response to complications, the decreased sensitivity inherent to using a general
      satisfaction survey, or a homogeneity among orthopedic surgery patients and their
      expectations of care.

PMID- 24033918
TI  - Inflammatory changes with features of chronic leukocytoclastic vasculitis in a
      Spitz nevus.

PMID- 24033919
TI  - Surveillance transbronchial biopsies in infant lung and heart-lung transplant
      recipients: practice, safety and value.

PMID- 24033920
TI  - Distinct microscopic features of perineural invasion in adenoid cystic carcinoma
      of the head and neck.

PMID- 24033921
TI  - Stapled vs hand suture closure of loop ileostomy: a meta-analysis.
AB  - AIM: Loop ileostomies are widely used in colorectal surgery to reduce the
      consequences of distal anastomotic failure. The optimal surgical technique for
      their closure has yet not been defined. A meta-analysis was performed to compare
      the outcome after stapled or hand sutured ileostomy closure. METHOD: An
      electronic literature search of EMBASE, PubMed and the Cochrane Library was
      undertaken to identify studies reporting stapled and hand sutured ileostomy
      closure. End-points included postoperative small bowel obstruction (SBO),
      anastomotic leakage, wound infection, overall postoperative complications,
      operation time, hospital stay and surgery-related cost. RESULTS: Fourteen studies
      including 5084 patients were identified. Meta-analysis showed that stapled
      closure was associated with a lower rate of SBO overall (OR = 0.56, P < 0.00001)
      and early (within 30 days of closure) SBO (OR = 0.51, P < 0.00001). This
      difference persisted for direct ileostomy closure (OR = 0.62, P = 0.02) or
      closure with bowel resection and hand sewn anastomosis (OR = 0.44, P < 0.00001).
      Stapled closure required a shorter inpatient stay (mean difference -1.22, P <
      0.0001) and operating time (mean difference -11.21, P = 0.01). No significant
      difference was noted between the two techniques in terms of anastomotic leakage,
      wound infection, overall complications or cost. CONCLUSION: Stapled side-to-side
      anastomosis is associated with fewer complications, especially SBO, than hand
      sewn ileostomy closure by direct suture or resection and anastomosis. It is
      quicker to perform and associated with fewer postoperative bowel obstructions.

PMID- 24033922
TI  - Contact dissociation from paddle leads: a report of two cases.

PMID- 24033923
TI  - Immune cell-derived C3a and C5a costimulate human T cell alloimmunity.
AB  - Emerging evidence indicates that complement provides costimulatory signals for
      murine T cells but whether complement impacts human T cells remains unclear. We
      observed production of complement activation products C3a and C5a during in vitro
      cultures of human T cells responding to allogeneic dendritic cells (DC). Both
      partners expressed the receptors for C3a (C3aR) and C5a (C5aR) and C3aR- and C5aR
      antagonists inhibited T cell proliferation. Recombinant C3a/C5a promoted CD4(+) T
      cell expansion, bypassed the inhibitory effects of CTLA4-Ig, and induced AKT
      phosphorylation, the latter biochemically linking C3aR/C5aR to known T cell
      signaling pathways. Lowering DC C3a/C5a production by siRNA knockdown of DC C3
      reduced T cell alloresponses. Conversely downregulating DC expression of the
      complement regulatory protein decay-accelerating factor increased immune cell
      C3a/C5a and augmented T cell proliferation, identifying antigen presenting cells
      as the dominant complement source. Pharmacological C5aR blockade reduced graft
      versus host disease (GVHD) scores, prolonged survival, and inhibited T cell
      responses in NOD scid gammac(null) mouse recipients of human peripheral blood
      mononuclear cells, verifying that the mechanisms apply in vivo. Together our
      findings unequivocally document that immune cell-derived complement impacts human
      T cell immunity and provide the foundation for future studies targeting C3aR/C5aR
      as treatments of GVHD and organ transplant rejection in humans.

PMID- 24033925
TI  - A fragile bond: adoptive parents' experiences of caring for children with a
      diagnosis of reactive attachment disorder.
AB  - AIMS AND OBJECTIVES: To understand how adoptive parents caring for children with
      a diagnosis of reactive attachment disorder (RAD) make sense of their life-worlds
      by establishing the meanings that underlie and structure their experiences of
      their everyday lives. BACKGROUND: Reactive attachment disorder is a serious
      psychosocial disorder of childhood that causes short- and long-term relationship,
      health and social consequences for children. It is more likely to be observed in
      children being cared for by foster carers, kinship carers or adoptive parents.
      Exploration of adoption from parents' perspectives is not well documented, and no
      previous work has been undertaken to understand the challenges of caring for
      children with a diagnosis of reactive attachment disorder. DESIGN: The study was
      guided by Husserl's phenomenology, which aims to uncover the underlying essential
      meanings intrinsic to a phenomenon. Three concepts are central to this approach:
      essences, intuiting and eidetic reduction. METHODS: Semi-structured interviews
      were conducted with eight adoptive parents. Data were analysed using an
      adaptation of Colaizzi's method. RESULTS: Four essential elements fundamental to
      participants' lived experiences of caring for a child with a diagnosis of RAD
      were uncovered: being profoundly unprepared, being insecure, being assailed by
      unexpected emotions and being committed. CONCLUSIONS: The parent-child
      relationship is a fragile bond developed at an unexpectedly high personal cost;
      it is a committed relationship but vulnerable to continual destabilisation. The
      involvement in the preparation of adoptive parents of child and adolescent mental
      health (CAMH) staff with expertise in the impact of early neglect or separation
      on children should be considered. RELEVANCE TO CLINICAL PRACTICE: The development
      of systems to prepare, screen and identify potential challenges and problems
      prior to adoption might help adoptive parents. Access to a CAMH professional in
      the pre and postadoption phases might assist potential adoptive parents in making
      informed decisions around the choice of a child for adoption.

PMID- 24033924
TI  - Glycolytic fast-twitch muscle fiber restoration counters adverse age-related
      changes in body composition and metabolism.
AB  - Aging is associated with the development of insulin resistance, increased
      adiposity, and accumulation of ectopic lipid deposits in tissues and organs.
      Starting in mid-life there is a progressive decline in lean muscle mass
      associated with the preferential loss of glycolytic, fast-twitch myofibers.
      However, it is not known to what extent muscle loss and metabolic dysfunction are
      causally related or whether they are independent epiphenomena of the aging
      process. Here, we utilized a skeletal-muscle-specific, conditional transgenic
      mouse expressing a constitutively active form of Akt1 to examine the consequences
      of glycolytic, fast-twitch muscle growth in young vs. middle-aged animals fed
      standard low-fat chow diets. Activation of the Akt1 transgene led to selective
      skeletal muscle hypertrophy, reversing the loss of lean muscle mass observed upon
      aging. The Akt1-mediated increase in muscle mass led to reductions in fat mass
      and hepatic steatosis in older animals, and corrected age-associated impairments
      in glucose metabolism. These results indicate that the loss of lean muscle mass
      is a significant contributor to the development of age-related metabolic
      dysfunction and that interventions that preserve or restore fast/glycolytic
      muscle may delay the onset of metabolic disease. 

PMID- 24033926
TI  - Diabetic retinopathy risk prediction for fundus examination using sparse
      learning: a cross-sectional study.
AB  - BACKGROUND: Blindness due to diabetic retinopathy (DR) is the major disability in
      diabetic patients. Although early management has shown to prevent vision loss,
      diabetic patients have a low rate of routine ophthalmologic examination. Hence,
      we developed and validated sparse learning models with the aim of identifying the
      risk of DR in diabetic patients. METHODS: Health records from the Korea National
      Health and Nutrition Examination Surveys (KNHANES) V-1 were used. The prediction
      models for DR were constructed using data from 327 diabetic patients, and were
      validated internally on 163 patients in the KNHANES V-1. External validation was
      performed using 562 diabetic patients in the KNHANES V-2. The learning models,
      including ridge, elastic net, and LASSO, were compared to the traditional
      indicators of DR. RESULTS: Considering the Bayesian information criterion, LASSO
      predicted DR most efficiently. In the internal and external validation, LASSO was
      significantly superior to the traditional indicators by calculating the area
      under the curve (AUC) of the receiver operating characteristic. LASSO showed an
      AUC of 0.81 and an accuracy of 73.6% in the internal validation, and an AUC of
      0.82 and an accuracy of 75.2% in the external validation. CONCLUSION: The sparse
      learning model using LASSO was effective in analyzing the epidemiological
      underlying patterns of DR. This is the first study to develop a machine learning
      model to predict DR risk using health records. LASSO can be an excellent choice
      when both discriminative power and variable selection are important in the
      analysis of high-dimensional electronic health records.

PMID- 24033927
TI  - Perception of soft mechanical stress in Arabidopsis leaves activates disease
      resistance.
AB  - BACKGROUND: In a previous study we have shown that wounding of Arabidopsis
      thaliana leaves induces a strong and transient immunity to Botrytis cinerea, the
      causal agent of grey mould. Reactive oxygen species (ROS) are formed within
      minutes after wounding and are required for wound-induced resistance to B.
      cinerea. RESULTS: In this study, we have further explored ROS and resistance to
      B. cinerea in leaves of A. thaliana exposed to a soft form of mechanical
      stimulation without overt tissue damage. After gentle mechanical sweeping of leaf
      surfaces, a strong resistance to B. cinerea was observed. This was preceded by a
      rapid change in calcium concentration and a release of ROS, accompanied by
      changes in cuticle permeability, induction of the expression of genes typically
      associated with mechanical stress and release of biologically active diffusates
      from the surface. This reaction to soft mechanical stress (SMS) was fully
      independent of jasmonate (JA signaling). In addition, leaves exposed soft
      mechanical stress released a biologically active product capable of inducing
      resistance to B. cinerea in wild type control leaves. CONCLUSION: Arabidopsis can
      detect and convert gentle forms of mechanical stimulation into a strong
      activation of defense against the virulent fungus B. cinerea.

PMID- 24033928
TI  - Unraveling enzyme discrimination during cellulosome assembly independent of
      cohesin-dockerin affinity.
AB  - Bacterial cellulosomes are generally believed to assemble at random, like those
      produced by Clostridium cellulolyticum. They are composed of one scaffolding
      protein bearing eight homologous type I cohesins that bind to any of the type I
      dockerins borne by the 62 cellulosomal subunits, thus generating highly
      heterogeneous complexes. In the present study, the heterogeneity and random
      assembly of the cellulosomes were evaluated with a simpler model: a
      miniscaffoldin containing three C. cellulolyticum cohesins and three cellulases
      of the same bacterium bearing the cognate dockerin (Cel5A, Cel48F, and Cel9G).
      Surprisingly, rather than the expected randomized integration of enzymes, the
      assembly of the minicellulosome generated only three distinct types of complex
      out of the 10 possible combinations, thus indicating preferential integration of
      enzymes upon binding to the scaffoldin. A hybrid scaffoldin that displays one
      cohesin from C. cellulolyticum and one from C. thermocellum, thus allowing
      sequential integration of enzymes, was exploited to further characterize this
      phenomenon. The initial binding of a given enzyme to the C. thermocellum cohesin
      was found to influence the type of enzyme that subsequently bound to the C.
      cellulolyticum cohesin. The preferential integration appears to be related to the
      length of the inter-cohesin linker. The data indicate that the binding of a
      cellulosomal enzyme to a cohesin has a direct influence on the dockerin-bearing
      proteins that will subsequently interact with adjacent cohesins. Thus, despite
      the general lack of specificity of the cohesin-dockerin interaction within a
      given species and type, bacterial cellulosomes are not necessarily assembled at
      random.

PMID- 24033929
TI  - Both extracellular chitinase and a new cyclic lipopeptide, chromobactomycin,
      contribute to the biocontrol activity of Chromobacterium sp. C61.
AB  - Chromobacterium sp. strain C61 displays antifungal activities in vitro and has
      been used successfully for the biocontrol of plant diseases under field
      conditions. In this study, the roles of extracellular chitinase and an antifungal
      compound produced by strain C61 were investigated to elucidate their
      contributions to biological control activity. The bacterium possessed a locus
      chi54 encoding an extracellular chitinase, and mutation of chi54 eliminated
      chitinase production. Production of the extracellular enzyme and expression of
      the chi54 transcript were increased in the wild-type strain when chitin was added
      to the culture medium. In vitro assays showed that purified chitinase inhibited
      spore germination of multiple pathogens. However, the in planta biocontrol
      activity of filtrates of cultures grown in the presence of chitin was lower than
      that of filtrates grown without chitin, indicating that correlation between
      chitinase and biocontrol activity was lacking. The analysis of C61 culture
      filtrates revealed an antifungal cyclic lipopeptide, chromobactomycin, whose
      structure contained a unique nonameric peptide ring. The purified
      chromobactomycin inhibited the growth of several phytopathogenic fungi in vitro,
      and plant application significantly reduced disease severity for several
      pathogens. Furthermore, the production of chromobactomycin was reduced in
      cultures amended with chitin. These data suggest that the production of both the
      extracellular chitinase Chi54 and the newly identified antibiotic
      chromobactomycin can contribute, in an interconnected way, to the suppression of
      plant disease by Chromobacterium sp. strain C61.

PMID- 24033930
TI  - Efficacy and long-term outcomes of radiofrequency ablation in the elderly with
      hepatocellular carcinoma.
AB  - AIM: The use of radiofrequency ablation (RFA) in elderly patients is increasing
      in those with hepatocellular carcinoma (HCC). This study compares the elderly
      (>=75 years old) to non-elderly patients (<75 years old) in the outcomes of the
      efficacy and safety of RFA. METHODS: Three hundred and thirty-five patients, 103
      elderly and 232 non-elderly, with naive HCC who were treated with RFA from 1999
      to 2012 were enrolled. Patient characteristics, complications, length of hospital
      stay, overall survival (OS), median survival time (MST), recurrence-free survival
      (RFS) and factors related to OS were analyzed. RESULTS: Median age was 79 years
      (range, 75-88) in the elderly group and 65 years (38-74) in the non-elderly
      group. The proportion of women (45.6% and 28.0%), hepatitis C virus infection
      (63.1% and 50.4%) and comorbidities (78.6% and 44.0%) in the elderly group
      compared to the non-elderly group, respectively, was significantly higher. No
      difference existed in the complications and length of hospital stay. The 5-year
      OS rates and MST were 67.3% and 90.5 months in the elderly group and 60.9% and
      86.4 months in the non-elderly group, respectively (P = 0.486). The median RFS
      time was 20 months in the elderly group and 18.7 months in the non-elderly group
      (P = 0.429). In multivariate analysis, the Child-Pugh grade and tumor-node
      metastasis stage were significantly associated with OS (P < 0.001, =0.003); age
      was not (P = 0.355). CONCLUSION: RFA in elderly patients is as effective and safe
      as in non-elderly patients for the treatment of HCC.

PMID- 24033931
TI  - A safety evaluation of the intravitreal use of a beta-2 agonist in rabbit eyes.

PMID- 24033932
TI  - A case-control study on serum antioxidants status (Se, Zn, and Cu) in children
      with chronic myeloid leukemia.

PMID- 24033933
TI  - The Motivation-Facilitation Theory of Prenatal Care Access.
AB  - Despite the availability of services, accessing health care remains a problem in
      the United States and other developed countries. Prenatal care has the potential
      to improve perinatal outcomes and decrease health disparities, yet many women
      struggle with access to care. Current theories addressing access to prenatal care
      focus on barriers, although such knowledge is minimally useful for clinicians. We
      propose a middle-range theory, the motivation-facilitation theory of prenatal
      care access, which condenses the prenatal care access process into 2 interacting
      components: motivation and facilitation. Maternal motivation is the mother's
      desire to begin and maintain care. Facilitation represents the goal of the clinic
      to create easy, open access to person-centered beneficial care. This simple model
      directs the focus of research and change to the interface of the woman and the
      clinic and encourages practice-level interventions that facilitate women entering
      and maintaining prenatal care. 

PMID- 24033934
TI  - X-ray crystallographic and fluorometric analysis of the interactions of rhein to
      human serum albumin.
AB  - To investigate the interactions between natural drugs and human serum albumin
      (HSA), we performed fluorescence spectroscopy and X-ray crystallography to gain
      insight into binding mechanism and behaviour of rhein to HSA. Our fluorescence
      results demonstrated that rhein strongly binds with HSA, and other compounds may
      affect binding affinity of rhein to different extent. Structural analysis
      revealed that rhein binds to the IIA subdomain of HSA. The carboxylate group of
      rhein forms hydrogen bonds with Arg218 and Lys199, as well as a salt bond with
      Arg222. Hydroxyl group (4) of rhein forms a hydrogen bond with His242, and
      hydroxyl group (5) of rhein forms a hydrogen bond with Arg257. Oxygen atom (7) of
      rhein forms a hydrogen bond with Arg222, and oxygen atom (6) of rhein forms a
      hydrogen bond with H2O. Furthermore, hydroxyl group (4) of rhein also forms a
      hydrogen bond with H2O. Our results reveal the biochemical and structural
      characteristics of the interaction between rhein and HSA, providing guidance for
      future development of rhein-based compounds and a drug-HSA delivery system.

PMID- 24033935
TI  - Light regulates motility, attachment and virulence in the plant pathogen
      Pseudomonas syringae pv tomato DC3000.
AB  - Pseudomonas syringae pv tomato DC3000 (Pto) is the causal agent of the bacterial
      speck of tomato, which leads to significant economic losses in this crop. Pto
      inhabits the tomato phyllosphere, where the pathogen is highly exposed to light,
      among other environmental factors. Light represents a stressful condition and
      acts as a source of information associated with different plant defence levels.
      Here, we analysed the presence of both blue and red light photoreceptors in a
      group of Pseudomonas. In addition, we studied the effect of white, blue and red
      light on Pto features related to epiphytic fitness. While white and blue light
      inhibit motility, bacterial attachment to plant leaves is promoted. Moreover,
      these phenotypes are altered in a blue-light receptor mutant. These light
      controlled changes during the epiphytic stage cause a reduction in virulence,
      highlighting the relevance of motility during the entry process to the plant
      apoplast. This study demonstrated the key role of light perception in the Pto
      phenotype switching and its effect on virulence. 

PMID- 24033936
TI  - Reform direction of medical education in China: implementing "competency-based"
      medical education.

PMID- 24033937
TI  - Association of chronic obstructive pulmonary disease with coronary artery
      disease.
AB  - BACKGROUND: The relationship between chronic obstructive pulmonary disease (COPD)
      and coronary artery disease (CAD) remains largely unknown. This study aimed to
      explore the association of COPD with CAD, especially with multi-vessel disease
      (VD). METHODS: The data of 354 patients who underwent multi-detector computed
      tomography (MDCT) for suspected CAD were analyzed. Luminal narrowing was defined
      as at least one lesion 50% or greater stenosis. The analysis of serum
      biochemistry profile and spirometry were performed on all eligible patients, and
      the diagnosis of COPD was defined as the criteria of Global Initiative for
      Chronic Obstructive Lung Disease. RESULTS: Patients with CAD had a significantly
      higher complication of COPD than those without CAD (11.8% vs. 3.7%, P < 0.001).
      Comparing with patients without COPD, those with COPD were more likely to have
      multi-VD, proportion of smoking and high C-reactive protein (CRP) (P < 0.001).
      Multivariate Logistic regression analysis revealed that the multi-VD was
      significantly correlated with COPD (P=0.012) and CRP (P=0.015). CONCLUSIONS:
      There was a high complication of COPD in patients with CAD, and COPD may be a
      critical risk factor for CAD, especially for multi-VD. CAD and COPD were closely
      associated and the interplay of systemic inflammation might in part explain the
      relationship between them.

PMID- 24033938
TI  - Pneumonia relevant to lung transplantation and pathogen distribution.
AB  - BACKGROUND: Pneumonia is the most common cause of morbidity and mortality in lung
      transplant (LT) recipients. The aim of the present study was to evaluate the
      incidence, etiology, risk factors and prognosis of pneumonia in LT recipients.
      METHODS: The LT cohort consisted of 28 recipients receiving LT in Beijing Chao
      Yang Hospital from August 2005 to April 2011. Data collected included demographic
      data, underlying disorders, time and type of transplant, follow-up information,
      date of last follow-up, and patient status. A retrospective analysis was made of
      observational data that were prospectively collected. RESULTS: Twenty-two
      patients of 28 LT recipients had 47 episodes of pneumonia throughout the study
      period. Thirtyeight episodes of pneumonia in 19 recipients occurred post-LT with
      a median follow-up of 257.5 days (1-2104 days), the incidence of pneumonia was
      192.4 episodes per 100 LT/year and its median time of onset was 100.5 days (0-946
      days) post-transplantation. Bacteria, virus and fungi accounted for 62%, 16% and
      15% of the microbial pathogens, respectively. The most frequent were Pseudomonas
      aeruginosa (20%), cytomegalovirus (CMV) (15%), and Aspergillus fumigatus (10%). A
      total of 29% (11/38) of pneumonias occurred in the first month post-LT, and then
      the incidence decreased gradually. The incidence of CMV pneumonia was 25% (7/28)
      with a median time of 97 days (10-971 days). More than one bacterial infection
      and CMV infection were independent risk factors for aspergillus infection. The
      incidence of pulmonary tuberculosis (TB) was 18% (5/28), and the history of TB
      was a risk factor for TB relapse. There were 58% (7/12) of recipients who died of
      infection, and 71% (5/7) of these died in the first year after LT. CONCLUSIONS:
      Pneumonia is still a major cause of morbidity and mortality in LT recipients. The
      most frequent microorganisms were Pseudomonas aeruginosa, CMV, and Aspergillus
      fumigates. The incidence of CMV pneumonia decreases with a delayed median time of
      onset. More than one incidence of bacterial infection and CMV infection are
      independent risk factors for aspergillus infection. LT recipients are at high
      risk for TB, and the history of TB is a risk factor for TB relapse.

PMID- 24033939
TI  - Combined detections of interleukin 27, interferon-gamma, and adenosine deaminase
      in pleural effusion for diagnosis of tuberculous pleurisy.
AB  - BACKGROUND: Previous studies reported interleukin-27 (IL-27), interferon-gamma
      (IFN-gamma), or adenosine deaminase (ADA) alone plays a helpful role in
      diagnosing tuberculous pleural effusion (TPE). The present study aims at
      comparing the diagnostic accuracy of pleural IL-27, IFN-gamma, and ADA, and
      investigate the diagnostic accuracy of the combination of IL-27, IFN-gamma,
      or/and ADA for differentiating TPE from pleural effusions with the other
      etiologies. METHODS: The concentrations of IL-27, IFN-gamma and ADA were
      simultaneously determined in pleural fluids and sera from 40 patients with TPE;
      26 with malignant pleural effusion, seven with infectious pleural effusion, and
      eight with transudative pleural effusion by enzyme linked immunosorbent assay and
      colorimetric method. The corresponding biochemical indexs were also
      simultaneously determined. RESULTS: The concentrations of pleural IL-27 and IFN
      gamma in the tuberculous group were significantly higher than those in the
      malignant, infectious, and transudative groups. The concentrations of ADA in TPE
      were significantly higher than those in MPE or transudative effusions, while much
      lower than those in infectious effusions. Among these three biomarkers, IL-27 was
      the most effective for TPE diagnosis, with the cut off value of 900.8 ng/L. IL-27
      had a high sensitivity of 95% and specificity of 97.6% for differential diagnosis
      of TPE from non-TPEs. Combinations of IL-27, IFN-gamma and ADA measurements
      further increased the sensitivity or specificity up to 100%. CONCLUSIONS:
      Compared to non-TPEs, IL-27, IFN-gamma and ADA all simultaneously increased in
      TPE; and among these three rapid detection methods, IL-27 appeared to be the best
      for distinguishing tuberculous from non-TPEs, especially from MPE. Combinations
      of the three markers (IL-27, IFN-gamma and ADA) yielded the highest sensitivity
      and specificity. These findings suggest that the applications of a new biomarker,
      IL-27, alone or with IFN-gamma and ADA, may contribute to more efficient
      diagnosis strategies in the management of tuberculous pleurisy.

PMID- 24033940
TI  - Decreased and dysfunctional circulating endothelial progenitor cells in patients
      with chronic obstructive pulmonary disease.
AB  - BACKGROUND: It has been widely demonstrated that endothelial progenitor cells are
      involved in several diseases and that they have therapeutic implications. In
      order to define the altered pulmonary vascular homeostasis in chronic obstructive
      pulmonary disease, we sought to observe the level and functions of circulating
      endothelial progenitor cells in patients with chronic obstructive pulmonary
      disease. METHODS: The total study population included 20 patients with chronic
      obstructive pulmonary disease and 20 control subjects. The number of circulating
      endothelial progenitor cells (CD34(+)/CD133(+)/VEGFR-2(+) cells) was counted by
      flow cytometry. Circulating endothelial progenitor cells were also cultured in
      vitro and characterized by uptake of DiIacLDL, combining with UEA-I, and
      expression of von Willebrand factor and endothelial nitric oxide synthase.
      Adhesion, proliferation, production of nitric oxide, and expression of
      endothelial nitric oxide synthase and phosphorylated-endothelial nitric oxide
      synthase were detected to determine functions of circulating endothelial
      progenitor cells in patients with chronic obstructive pulmonary disease. RESULTS:
      The number of circulating endothelial progenitor cells in the chronic obstructive
      pulmonary disease group was lower than in the control group: (0.54 +/- 0.16)% vs.
      (1.15 +/- 0.57)%, P < 0.05. About 80% of adherent peripheral blood mononuclear
      cells cultured in vitro were double labeled with Dil-acLDL and UEA-1. The 92% and
      91% of them were positive for von Willebrand factor and endothelial nitric oxide
      synthase, respectively. Compared with the control, there were significantly fewer
      adhering endothelial progenitor cells in chronic obstructive pulmonary disease
      patients: 18.7 +/- 4.8/field vs. 45.0 +/- 5.9/field, P < 0.05. The proliferation
      assay showed that the proliferative capacity of circulating endothelial
      progenitor cells from chronic obstructive pulmonary disease patients was
      significantly impaired: 0.135 +/- 0.038 vs. 0.224 +/- 0.042, P < 0.05.
      Furthermore, nitric oxide synthase (112.06 +/- 10.00 vs. 135.41 +/- 5.38, P <
      0.05), phosphorylated endothelial nitric oxide synthase protein expression (88.89
      +/- 4.98 vs. 117.98 +/- 16.49, P < 0.05) and nitric oxide production ((25.11 +/-
      5.27) umol/L vs. (37.72 +/- 7.10) umol/L, P < 0.05) were remarkably lower in
      endothelial cells from the chronic obstructive pulmonary disease group than the
      control. CONCLUSION: Circulating endothelial progenitor cells were decreased and
      functionally impaired in patients with chronic obstructive pulmonary disease.

PMID- 24033941
TI  - Computed tomography in predicting smear-negative pulmonary tuberculosis in AIDS
      patients.
AB  - BACKGROUND: The correct diagnosis of sputum smear-negative pulmonary tuberculosis
      in AIDS patients is very important to their therapy. We aimed to assess the value
      of the computed tomography (CT) and clinical findings in predicting smear
      negative pulmonary tuberculosis in AIDS patients. METHODS: A total of 121 AIDS
      patients suspected of smear-negative pulmonary tuberculosis by clinical and
      radiographic findings were recruited. Pulmonary tuberculosis was diagnosed in 57
      (47.1%) patients. The CT and clinical predictors were selected to diagnose AIDS
      related pulmonary tuberculosis through univariate and multivariate Logistic
      analysis. RESULTS: Multivariate analysis showed that five variables, including
      weight loss, presence of miliary nodules, necrotic lymph node, lobular
      consolidation, tree-in-bud sign, were independent predictors of pulmonary
      tuberculosis in AIDS patients. Predicted scores based on the five variables were
      used to identify pulmonary tuberculosis. If the predicted score of 3 was taken as
      the ideal cut-off point in the diagnosis of AIDS-related smear-negative pulmonary
      tuberculosis, the sensitivity, specificity, positive predictive value, negative
      predictive value, and accuracy were 84.2%, 81.2%, 80.0%, 85.2%, and 82.6%,
      respectively. CONCLUSION: The prediction method based on five key factors of
      clinical and CT findings are useful in guiding the diagnosis of smear-negative
      pulmonary tuberculosis in AIDS patients.

PMID- 24033942
TI  - Positive end expiratory pressure titrated by transpulmonary pressure improved
      oxygenation and respiratory mechanics in acute respiratory distress syndrome
      patients with intra-abdominal hypertension.
AB  - BACKGROUND: Intra-abdominal hypertension (IAH) is common in acute respiratory
      distress syndrome (ARDS) patients and when resulting in decrease of chest wall
      compliance will weaken the effect of positive end expiratory pressure (PEEP). We
      investigated the effect of PEEP titrated by transpulmonary pressure (Ptp) on
      oxygenation and respiratory mechanics in ARDS patients with IAH compared with
      PEEP titrated by ARDSnet protocol. METHODS: ARDS patients admitted to the
      intensive care unit (ICU) of the Zhongda Hospital were enrolled. Patients were
      ventilated with volume control mode with tidal volume of 6 ml/kg under two
      different PEEP levels titrated by Ptp method and ARDSnet protocol. Respiratory
      mechanics, gas exchange and haemodynamics were measured after 30 minutes of
      ventilation in each round. IAH was defined as intra-abdominal pressure of 12 mmHg
      or more. RESULTS: Seven ARDS patients with IAH and 8 ARDS patients without IAH
      were enrolled. PEEP titrated by Ptp were significant higher than PEEP titrated by
      ARDSnet protocol in both ARDS patients with IAH ((17.3 +/- 2.6) cmH2O vs. (6.3 +/
      1.6) cmH2O and without IAH ((9.5 +/- 2.1) cmH2O vs. (7.8 +/- 1.9) cmH2O).
      Arterial pressure of O2/fraction of inspired oxygen (PaO2/FiO2) was much higher
      under PEEP titrated by Ptp when compared with PEEP titrated by ARDSnet protocol
      in ARDS patients with IAH ((27.2 +/- 4.0) cmHg vs. (20.9 +/- 5.0) cmHg. But no
      significant difference of PaO2/FiO2 between the two methods was found in ARDS
      patients without IAH. In ARDS patients with IAH, static compliance of lung and
      respiratory system were higher under PEEP titrated by Ptp than by ARDSnet
      protocol. In ARDS patients with IAH, central venous pressure (CVP) was higher
      during PEEP titrated by Ptp than by ARDSnet protocol. CONCLUSION: Positive end
      expiratory pressure titrated by transpulmonary pressure was higher than PEEP
      titrated by ARDSnet protocol and improved oxygenation and respiratory mechanics
      in ARDS patients with IAH.

PMID- 24033943
TI  - Exhaled hydrogen sulfide in patients with chronic obstructive pulmonary disease
      and its correlation with exhaled nitric oxide.
AB  - BACKGROUND: Exhaled nitric oxide (NO) is a noninvasive biomarker of airway
      inflammation in pulmonary diseases. Hydrogen sulfide (H2S), as the third member
      of the gasotransmitter family, is involved in the pathophysiological process in
      lung diseases. H2S also exists in exhaled breath and can be sampled non
      invasively. The study investigated the level of exhaled H2S in patients with
      chronic obstructive pulmonary disease (COPD) and its correlation with exhaled NO.
      METHODS: Levels of exhaled NO and H2S, lung function, and cell differential
      counts in induced sputum were studied in 19 patients with acute exacerbation of
      COPD (AECOPD), 19 patients with stable COPD and seven healthy smoke controls.
      RESULTS: Exhaled H2S levels were similar in patients with AECOPD (10.0 parts per
      billion (ppb), 8.0-13.0 ppb), stable COPD (10.0 ppb, 9.0-12.0 ppb), and healthy
      controls (9.0 ppb, 8.0-16.0 ppb) (P > 0.05). Exhaled NO levels were similar in
      patients with AECOPD (155.0 ppb, 129.0-190.0 ppb), stable COPD (154.0 ppb, 133.0
      175.0 ppb) and healthy controls (165.0 ppb, 112.0-188.0 ppb) (P > 0.05). Exhaled
      H2S levels correlated positively with exhaled NO in all healthy controls and
      patients with COPD (r=0.467, P < 0.01). No significant correlation was found
      between the exhaled H2S level and percentage of predicted FEV1 (P > 0.05) and
      proportion of different cell types in induced sputum (P > 0.05). CONCLUSIONS:
      There is a correlation between exhaled H2S and exhaled NO. The role of exhaled
      H2S in airway inflammation in COPD still needs further investigation.

PMID- 24033944
TI  - Correlation of Epworth Sleepiness Scale with multiple sleep latency test and its
      diagnostic accuracy in assessing excessive daytime sleepiness in patients with
      obstructive sleep apnea hypopnea syndrome.
AB  - BACKGROUND: Excessive daytime sleepiness (EDS) is often associated with
      obstructive sleep apnea hypopnea syndrome (OSAHS) and contributes to a number of
      comorbidities in these patients. Therefore, early detection of EDS is critical in
      disease management. We examined the association between Epworth Sleepiness Scale
      (ESS) and multiple sleep latency test (MSLT) and diagnostic accuracy of ESS in
      assessing EDS in OSAHS patients. METHODS: The ESS, MSLT and overnight
      polysomnography were administered to 107 Chinese patients to assess EDS and its
      correlations with polysomnographic parameters. The diagnostic accuracy of ESS in
      classifying EDS (mean sleep latency (MSL) <= 10 minutes) was evaluated by
      calculating the area under ROC curve. RESULTS: As the severity of OSAHS
      increased, MSL decreased with increase in ESS score. Conversely, patients with
      worsening EDS (shorter MSL) were characterized by advanced nocturnal hypoxaemia
      and sleep disruption compared to those with normal MSL, suggesting EDS is
      associated with more severe OSAHS. There was a negative correlation between ESS
      score and MSL and both moderately correlated with some polysomnographic nocturnal
      hypoxaemic parameters. The area under ROC curve of ESS for identifying EDS was
      0.80 (95% CI: 0.71 to 0.88) and ESS score >= 12 provided the best predictive
      value with a sensitivity of 80% and specificity of 69%. CONCLUSION: The ESS score
      moderately correlates with MSL and our ROC study supports ESS as a screening
      strategy for assessing EDS in OSAHS.

PMID- 24033945
TI  - ERK signaling mediates enhanced angiotensin II-induced rat aortic constriction
      following chronic intermittent hypoxia.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) has been recognized as an independent
      risk factor for systemic hypertension. The study investigated the functional
      consequences of chronic intermittent hypoxia (CIH) on aortic constriction induced
      by angiotensin II (Ang II) and the possible signaling involving ERK1/2 and
      contractile proteins such as myosin light chain kinase (MLCK), myosin phosphatase
      targeting subunit (MYPT1) and myosin light chain (MLC). METHODS: Male Wistar rats
      were randomly divided into CIH group and normoxia group and exposed to either CIH
      procedure or air-air cycles. Phosphorylation of ERK1/2, MYPT1 and MLC was
      assessed by Western blotting following constrictor studies in the presence or
      absence of PD98059 (10 umol/L). RESULTS: CIH-exposure resulted in more body
      weight gain and elevated blood pressure, which could be attenuated by
      pretreatment with PD98059. Endothelium-removed aortic rings from CIH rats
      exhibited higher constrictor sensitivity to Ang II (Emax: (138.56 +/- 5.78)%
      versus (98.45+/-5.31)% of KCl; pD2: 7.98 +/- 0.14 versus 8.14 +/- 0.05,
      respectively). CIH procedure exerted complex effects on ERK expressions (total
      ERK1/2 decreased whereas the ratio of phosphorylated to total ERK1/2 increased).
      CIH aortas had higher MLCK mRNA and basal phosphorylation of MYPT1 and MLC. In
      parallel to greater increases in phosphorylation of ERK1/2, MYPT1 and MLC, Ang II
      induced aortic constriction was significantly enhanced in CIH rats, which was
      largely reversed by PD98059. However vascular constriction of normoxia rats
      remained unchanged despite similar but smaller changing tendency of proteins
      phosphorylation. CONCLUSION: These data suggest that CIH exposure results in
      aortic hyperresponsiveness to Ang II, presumably owing to more activated ERK1/2
      signaling pathway.

PMID- 24033946
TI  - Adiponectin alleviates contractile dysfunction of genioglossus in rats exposed to
      chronic intermittent hypoxia.
AB  - BACKGROUND: Genioglossal dysfuntion takes an important role in pathogenesis of
      obstructive sleep apnea hypopnea syndrome (OSAHS) in which chronic intermittent
      hypoxia (CIH) is the major pathological origin. Recent studies have suggested
      genioglossal injury induced by CIH might be improved by adiponectin. The aim of
      this study was to investigate the effects of adiponectin on genioglossus
      contractile properties in rats exposed to CIH. METHODS: Thirty-nine healthy male
      Wistar rats were randomly divided into three groups: normal control (NC), CIH and
      adiponectin supplement (CIH+Ad) with 13 rats in each. Rats in NC were kept
      breathing normal air, while rats in CIH and CIH+Ad experienced the same CIH
      environment eight hours per day for 35 successive days. Rats in CIH+Ad were given
      intravenous adiponectin of 10 ug twice a week for 30 successive days. Rats in the
      NC and CIH were injected with normal saline as a control. After 35 days' CIH
      exposure, the levels of serum adiponectin and genioglossus contractile properties
      were compared. RESULTS: Serum adiponectin level was significantly lower in CIH
      than in NC (1210 ng/ml vs. 2236 ng/ml). Serum adiponectin level in CIH+Ad (1844
      ng/ml) was significantly higher than CIH but lower than NC. Twitch tension, time
      to peak tension, half relaxation time and tetanic tension were significantly
      lower in CIH than NC and improved in CIH+Ad. All mean tetanic fatigue indices
      decreased more rapidly in the first 20 seconds than during the subsequent 100
      seconds. Tetanic fatigue indices in NC and CIH+Ad were significantly higher
      compared to CIH. CONCLUSIONS: CIH could lead to hypoadiponectinaemia, impaired
      genioglossus contractile properties and decreased fatigue resistance in rats.
      Such changes could be partially offset by supplementation of adiponectin.

PMID- 24033947
TI  - Ang II type 1 receptor expression in rat aorta exposed to chronic intermittent
      hypoxia: effects of p38MAPK and ERK1/2 signaling.
AB  - BACKGROUND: Obstructive sleep apnea is a frequent medical condition consisting of
      repetitive sleep-related episodes of upper air ways obstruction and can lead to
      hypertension. Ang II type 1 receptor (AT1R) played important roles in
      hypertension since it binds with Ang II, controlling salt-water and blood
      pressure homeostasis. This study explores rat aorta AT1R expression during
      intermittent hypoxia (IH) and the signaling pathways involved. METHODS: A rat
      model and a cell model used a BioSpherix-OxyCycler A84 system and a ProOx C21
      system respectively. The arterial blood pressure was recorded by a Nihon Kohden
      Polygraph System. Immunohistochemic was used to focus and analyze the expression
      of AT1R in rat aorta. Real-time PCR and Western blotting were used to explore the
      signaling pathways that participated in AT1R expression. RESULTS: In this study,
      we found that chronic intermittent hypoxia (CIH) induced AT1R transcription which
      increased the blood pressure in rat aorta compared to normoxia and to sustained
      hypoxia. The AT1R protein expression in the aorta was similar to the real-time
      PCR results. We explored the signaling mechanisms involved in the AT1R induction
      in both rat aorta and the aortic endothelial cells by real-time PCR and Western
      blotting. Compared to normoxia, CIH increased ERK1 mRNA transcription but not
      ERK2 or p38MAPK in the aorta; whereas sustained hypoxia (SH) upregulated ERK2 but
      not ERK1 or p38MAPK mRNA. In cells, IH induced AT1R expression with ERK1/2
      phosphorylation but reduced p38MAPKs phosphorylation, whereas SH induced only
      ERK1/2 phosphorylation. The ERK1/2 inhibitor PD98059 attenuated the IHinduced
      AT1R increase but the p38MAPK inhibitor SB203580 did not. CONCLUSIONS: Our
      results indicate that CIH induced the elevation of rat blood pressure and aorta
      AT1R expression. Moreover, AT1R expression in IH and sustained hypoxia might be
      regulated by different signal transduction pathways, highlighting a novel
      regulatory function through ERK1/2 signaling in IH.

PMID- 24033948
TI  - Adiponectin protects the genioglossus of rats against chronic intermittent
      hypoxia-induced injury via inhibition of endoplasmic reticulum stress.
AB  - BACKGROUND: Obstructive sleep apnea hypopnea syndrome, characterized by chronic
      intermittent hypoxia (CIH), is closely correlated with genioglossus dysfunction.
      CIH has been identified to mediate mitochondrial damage in genioglossus. It has
      been reported that endoplasmic reticulum stress (ERS) could be induced by
      mitochondrial dysfunction. This study aimed to investigate the role of ERS in CIH
      induced genioglossus injury, as well as the possible intervention effect of
      adiponectin (Ad) supplement in rats. METHODS: Forty-five male Wistar rats were
      randomly divided into three groups and submitted to room air (group A, n=15) as a
      control or CIH (groups B and C, n=15, respectively). Throughout the exposure
      period, intravenous Ad was given in group C; while intravenous normal saline was
      simultaneously given in groups A and B. After 35-day exposure, genioglossus
      samples were obtained from the pentobarbital-anaesthetized rats via surgical
      dissection, following blood sampling. Western blotting was applied to detect
      expressions of ERS signals and associated apoptotic pathways in genioglossus.
      Serum adiponectin levels were assessed via enzyme-linked immunosorbent assay
      (ELISA). RESULTS: Significant hypoadiponectinemia was revealed in group B only (P
      < 0.05). Compared to those in groups A and C, expressions of markers involved in
      ERS, such as glucose regulated protein 78 (GRP78), p-PERK, phosphorylated
      eukaryotic initiation factor 2a (p-eIF2a), phosphorylated inositol-requiring
      transmembrane kinase/endoribonuclease 1a (p-IRE1a), spliced X-Box binding protein
      1 (XBP1s) and activating transcription factor 6 (ATF6), were significantly
      enhanced in group B (all P < 0.01); while no significant difference was shown
      between groups A and C (all P > 0.05). ERSassociated apoptotic pathways were
      remarkably activated in group B. The involved markers detected as the expression
      of CCAAT/enhancer binding protein homologous protein (CHOP), B-cell
      lymphoma/leukemia associatied X protein (BAX) and caspase-12 were significantly
      elevated (all P < 0.01). Transvenous adiponectin supplement improved the above
      CIHinduced pathological changes in group C. CONCLUSION: Beyond
      hypoadiponectinemia, CIH could enhance ERS and induce activation of ERS
      associated apoptotic pathways in genioglossus, which could be significantly
      improved by adiponectin supplement.

PMID- 24033949
TI  - Inhibition of nuclear factor-kappaB activity enhanced chemosensitivity to
      cisplatin in human lung adeno-carcinoma A549 cells under chemical hypoxia
      conditions.
AB  - BACKGROUND: Tumor hypoxia, one of the features of solid tumors, is associated
      with chemo-resistance. Recently, nuclear factor-kappaB (NF-kappaB) was found to
      be activated during hypoxia. However, the impact of NF-kappaB activation on chemo
      resistance during hypoxia remains unknown. METHODS: Human lung adenocarcinoma
      A549 cells were transfected with NF-kappaB p65siRNA and treated with cobalt
      chloride (CoCl2) to mimic hypoxia in the presence or absence of cisplatin. NF
      kappaB expression was measured by Western blotting, immune-fluorescence and real
      time PCR. Hypoxia-inducible factor-1alpha (HIF-1alpha) and Bcl-2 expression were
      determined by Western blotting. Cell apoptosis and survival with half-maximum
      inhibitory concentration (IC50) of cisplatin were determined by Annexin V-FITC/PI
      and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT),
      respectively. RESULTS: Exposure of A549 cells to CoCl2 increased nuclear HIF-1a
      protein expression, and enhanced NF-kappaB p65 protein nuclear accumulation (the
      mark of NF-kappaB activation) in a time and dose dependant manner. CoCl2 did not
      promote apoptosis in A549 cells; on the contrary, it reduced cisplatin-induced
      apoptosis and increased the IC50 of cisplatin. However, when we inhibited CoCl2
      induced activation of NF-kappaB through NF-kappaB p65siRNA, cisplatin-induced
      apoptosis was increased and IC50 of cisplatin was reduced to levels similar to
      those in control cells. Meanwhile, CoCl2-induced Bcl-2 overexpression was down
      regulated in the presence of cisplatin when NF-kappaB activity was inhibited.
      CONCLUSION: Up-regulating Bcl-2 might be involved in NF-kappaB activation induced
      resistance to cisplatin in A549 cells under CoCl2-induced chemical hypoxia.

PMID- 24033950
TI  - Murine calcium-activated chloride channel family member 3 induces asthmatic
      airway inflammation independently of allergen exposure.
AB  - BACKGROUND: Expression of murine calcium-activated chloride channel family member
      3 (mCLCA3) has been reported to be increased in the airway epithelium of
      asthmatic mice challenged with ovalbumin (OVA). However, its role in asthmatic
      airway inflammation under no OVA exposure has not yet been clarified. METHODS:
      mCLCA3 plasmids were transfected into the airways of normal BALB/c mice. mCLCA3
      expression and airway inflammation in mouse lung tissue were evaluated. Cell
      differentials and cytokines in bronchoalveolar lavage fluid (BALF) were analyzed.
      The expression of mCLCA3 protein and mucus protein mucin-5 subtype AC (MUC5AC)
      were analyzed by Western blotting. The mRNA levels of mCLCA3, MUC5AC and
      interleukin-13 (IL-13) were determined quantitatively. RESULTS: mCLCA3 expression
      was not detected in the control group while strong immunoreactivity was detected
      in the OVA and mCLCA3 plasmid groups, and was strictly localized to the airway
      epithelium. The numbers of inflammatory cells in lung tissue and BALF were
      increased in both mCLCA3 plasmid and OVA groups. The protein and mRNA levels of
      mCLCA3 and MUC5AC in the lung tissue were significantly increased in the mCLCA3
      plasmid and OVA groups compared to the control group. The level of IL-13, but not
      IL-4, IL-5, IFN-gamma, CCL2, CCL5 or CCL11, was significantly increased compared
      with control group in BALF in the mCLCA3 plasmid and OVA groups. The level of IL
      13 in the BALF in the mCLCA3 plasmid group was much higher than that in the OVA
      group (P < 0.05). The level of mCLCA3 mRNA in lung tissue was positively
      correlated with the levels of MUC5AC mRNA in lung tissue, IL-13 mRNA in lung
      tissue, the number of eosinophils in BALF, and the content of IL-13 protein in
      BALF. The level of IL-13 mRNA in lung tissue was positively correlated with the
      number of eosinophils in BALF and the level of MUC5AC mRNA in lung tissue.
      CONCLUSION: These findings suggest that increased expression of a single-gene,
      mCLCA3, could simulate an asthma attack, and its mechanism may involve mCLCA3
      overexpression up-regulating IL-13 expression.

PMID- 24033951
TI  - Dexamethasone enhances invasiveness of Aspergillus fumigatus conidia and
      fibronectin expression in A549 cells.
AB  - BACKGROUND: The efficacies of current treatments for invasive aspergillus (IA)
      are unsatisfactory and new therapeutic targets or regimens to treat IA are
      urgently needed. Previous studies have indicated that the ability of conidia to
      invade host cells is critical in IA development and fibronectin has a hand in the
      conidia adherence process. In the clinical setting, many patients who receive
      glucocorticoid for extended periods are susceptible to Aspergillus fumigatus (A.
      fumigatus) infection, for this reason we investigated the effect of
      glucocorticoid on conidia invasiveness by comparing the invasiveness of A.
      fumigatus conidia in the type II human alveolar cell line (A549) cultured with
      different concentrations of dexamethasone. We also explored the relationships
      between dexamethasone and fibronectin expression. METHODS: Following culture with
      anti-fibronectin antibodies and/or dexamethasone, type II human alveolar A549
      cells were infected with conidia of A. fumigatus. After 4 hours, the
      extracellular free conidia were washed away and the remaining immobilized conidia
      were released using Triton-X 100 and quantified by counting the colony-forming
      units. The invasiveness of conidia was measured by calculating the invasion rate
      (%). The transcription of the fibronectin gene in cells cultured with different
      concentrations of dexamethasone for 24 hours was tested by fluorogenic
      quantitative RT-PCR while the expression of fibronectinin cells cultured for 48
      hours was tested by Western blotting and immunocytochemistry. RESULTS: A
      significant reduction in the invasiveness of conidia was seen in the cells
      cultured with anti-fibronectin antibody ((14.42 +/- 1.68)% vs. (19.17 +/- 2.53)%,
      P < 0.05), but no significant difference was observed in cells cultured with a
      combination of anti-fibronectin antibody and dexamethasone (6.37 +/- 10(-5)
      mol/L). There was no correlation between the dexamethasone concentration and the
      invasiveness of conidia after dexamethasone pretreatment of cells for 4 hours. In
      contrast, after pretreated for 24 hours, the invasiveness of conidia in the
      presence of 6.37*10(-5) mol/L dexamethasone ((24.66 +/- 2.41)%) was higher than
      for the control ((19.17 +/- 2.53)%) and the 0.25*10(-5) mol/L group ((19.93 +/-
      3.06)%), and the invasiveness in the 1.27*10(-5) mol/L group ((22.47 +/- 2.46)%)
      was also higher than in the control, P < 0.05. The relative transcripts of the
      fibronectin gene after exposure to 6.37*10(-5) mol/L dexamethasone (9.19*10(-3)+/
      1.2*10(-3)) was higher than for the control (4.61*10(-3)+/- 1.54*10(-3)) and the
      0.25*10(-5) mol/L group (6.20*10(-3)+/- 1.93*10(-3)), and expression in the
      1.27*10(-5) mol/L group (7.94*10(-3)+/- 2.24*10(-3)) was also higher than for the
      control, P < 0.05. High concentrations of dexamethasone promoted fibronectin
      production after culture for 48 hours. CONCLUSIONS: Dexamethasone can increase
      invasiveness of A. fumigatus conidia by promoting fibronectin expression. This
      may partially explain why patients who are given large doses of glucocorticoids
      for extended periods are more susceptible to A. fumigatus infection.

PMID- 24033952
TI  - Glycated albumin may be a choice, but not an alternative marker of glycated
      hemoglobin for glycemic control assessment in diabetic patients undergoing
      maintenance hemodialysis.
AB  - BACKGROUND: It has been suggested that glycated hemoglobin (HbA1c) underestimate
      the actual glycemic control levels in maintenance hemodialysis (MHD) patients,
      because of anemia and the using of erythropoietin (EPO); it was recommended that
      glycated albumin (GA) should be an alternative marker. Therefore, the assessment
      performances of glycemic control were compared between GA and HbA1c in this
      research by referring to mean plasma glucose (MPG) in diabetes mellitus (DM)
      patients undergoing MHD or not. METHODS: MPG was calculated according to the data
      registered at enrollment and follow-up 2 months later and corresponding HbA1c,
      albumin (ALB), GA, etc. were measured in 280 cases. A case-control study for
      comparing GA and HbA1c was done among the groups of MHD patients with DM (n=88)
      and without DM (NDM; n=90), and non-MHD ones with DM (n=102) using MPG for an
      actual glycemic control standard. RESULTS: In these 3 groups, only for DM
      patients' (whether undergoing MHD or not), GA and HbA1c correlated with MPG
      significantly (P < 0.01). Through linear regression analysis, it could be found
      that the regression curves of GA almost coincided in MHD and non-MHD patients
      with DM, because the intercepts (2.418 vs. 2.329) and slopes (0.053 vs. 0.057)
      were very close to each other. On the contrary, regression curves of HbA1c did
      not coincide in the two groups, because variance of the slopes (0.036 vs. 0.052)
      were relatively large. Through comparing receiver operating characteristic (ROC)
      areas under the curve (AUC), it could be understood that the assessment
      performances of GA and HbA1c in MHD patients were lower than those in non-MHD
      ones, and assessment performance of HbA1c in MHD patients was better than GA (P <
      0.05). In addition, the effects of Hb and EPO dose on HbA1c, or that of ALB on GA
      were unobvious in our study. CONCLUSIONS: Actual glycemic control level in MHD
      patients with DM may be underestimated by HbA1c, and it could be avoided by GA;
      however, glycemic evaluating performance of HbA1c may be still better than that
      of GA. Therefore, HbA1c should not be replaced completely although GA can be used
      as a choice to monitor glycemic level.

PMID- 24033953
TI  - Clinical features of retinal diseases masquerading as retrobulbar optic neuritis.
AB  - BACKGROUND: Managements of optic neuritis (ON) included high-dose corticosteroids
      or combined with systemic immunomodulatory agents. It was important to make a
      correct diagnosis of ON before initiation of treatment. The purpose of the study
      was to report and analyze the clinical features of retinal diseases in patients
      who were misdiagnosed as having retrobulbar ON. METHODS: Retrospective review of
      26 patients (38 eyes) initially diagnosed with retrobulbar ON but were ultimately
      diagnosed with retinal or macular diseases. Data obtained from fundus
      examination, fluorescence fundus angiography (FFA), automated static perimetry,
      full-field electroretinogram (ffERG), multifocal electroretinogram (mfERG), and
      optical coherence tomography (OCT) were evaluated. RESULTS: Thirty-eight eyes of
      26 patients were found to have misdiagnosis of retrobulbar ON, based on normal or
      slight abnormal fundus findings and abnormal visual evoked potentials (VEP). The
      mean age of the patients was 34 years and the correct diagnosis of the patients
      included acute zonal occult outer retinopathy (AZOOR, 15 eyes, 14 patients),
      occult macular dystrophy (OMD, 8 eyes, 4 patients), cone or cone-rod dystrophy
      (10 eyes, 5 patients), acute macular neuroretinopathy (AMNR, 3 eyes, 2 patients),
      and cancer-associated retinopathy (CAR, 2 eyes, 1 patient). CONCLUSION: When
      attempting to diagnose retrobulbar ON in clinical practice, it is crucial to
      carry out necessary examinations of the retinal function and morphology to
      decrease misdiagnosis.

PMID- 24033954
TI  - Relationship between serum bilirubin levels and optic neuritis.
AB  - BACKGROUND: Bilirubin is the end product of heme catabolism and has strong
      antioxidant properties. Serum bilirubin levels are reported to be reduced in
      patients with multiple sclerosis (MS) and neuromyelitis optica (NMO). The
      pathophysiology of optic neuritis (ON) resembles that of MS; however, the role of
      endogenous bilirubin in ON is unclear. The aim of this study is to measure serum
      bilirubin levels in patients with ON, and to investigate the correlation between
      ON and serum antioxidant status of bilirubin. METHODS: Serum levels of bilirubin
      were measured in 42 patients with ON, 50 patients with multiple sclerosis (MS),
      48 patients with neuromyelitis optica (NMO) and 48 healthy control subjects.
      RESULTS: Serum total bilirubin (Tbil), direct bilirubin (Dbil) and indirect
      bilirubin (Ibil) levels in patients with ON were significantly lower than those
      in the healthy controls. However, no statistical significance was found between
      levels in the ON and MS, ON and NMO, and MS and NMO groups. In patients with ON,
      serum Tbil, Dbil, and Ibil levels were lower in those with recurrence or those
      with ON for a longer duration (>= 1 year). Moreover, Tbil, Dbil, and Ibil
      concentrations were lower in patients with papillitis than in those with
      retrobulbar type ON, but the differences were not statistically significant.
      CONCLUSIONS: Low antioxidant status may exist in patients with ON. But serum
      levels of Tbil, Dbil, and Ibil did not correlate with clinical presentations,
      such as recurrence, duration of disease and subtypes of ON. Low antioxidant
      status already existed in MS or NMO patients before systemic symptoms appeared.

PMID- 24033955
TI  - Association of CYBA rs7195830 polymorphism with estimated glomerular filtration
      rate in an adult Han sample from Jiangsu province, China.
AB  - BACKGROUND: Reactive oxygen species are thought to contribute to the development
      of renal damage. The P22phox subunit of nicotinamide adenine dinucleotide
      phosphate (NAPDH) oxidase, encoded by the cytochrome b245a polypeptide gene,
      CYBA, plays a key role in superoxide anion production. We investigated the
      association of CYBA rs7195830 polymorphism with estimated glomerular filtration
      rate (eGFR) and the role it plays in the pathogenesis of chronic kidney disease
      (CKD) in a Han Chinese sample. METHODS: The Gaoyou study enrolled 4473
      participants. Serum levels of creatinine were measured and eGFR was estimated
      using the Chronic Kidney Disease Epidemiology Collaboration equations. The CYBA
      polymorphisms were genotyped. Then we investigated the association between eGFR
      and the rs7195830 polymorphism in the recessive model. RESULTS: The AA genotype
      of rs7195830 was associated with significantly lower values of eGFR compared with
      the GG and AG genotypes ((102.76 +/- 17.07) ml*min(-1)*1.73 m(-2) vs. (105.08 +/-
      16.30) ml*min(-1)+/- 1.73 m(-2)). The association remained significant in the
      recessive model after adjusting for age, gender, body mass index, smoking,
      hypertension, diabetes mellitus, uric acid, triglyceride, low density lipoprotein
      cholesterol and high density lipoprotein cholesterol (beta=1.666, P=0.031). The
      rs7195832 AA genotype was an independent risk factor for CKD: eGFR <60 ml*min(
      1)*1.73 m(-2) (odds ratio=3.32; 95% CI=1.21-9.13). CONCLUSION: The AA genotype of
      rs7195830 is independently associated with lower estimated glomerular filtration
      rate and is significantly associated with CKD.

PMID- 24033956
TI  - Effects of nasal continuous positive airway pressure treatment on insulin
      resistance and ghrelin levels in non-diabetic apnoeic patients with coronary
      heart disease.
AB  - BACKGROUND: Obesity is a common risk factor for several diseases. Obesity related
      hormone and increased insulin resistance (IR) may contribute to the effects of
      obstructive sleep apnoea on cardiovascular consequences. We investigated ghrelin
      and IR in non-diabetic apnoeic patients with stable coronary heart disease and
      assessed the effects of continuous positive airway pressure (CPAP). METHODS:
      Plasma ghrelin, glucose and insulin were measured in 22 patients with CPAP and 22
      matched controls without CPAP at baseline and three months. Indexes including
      homeostasis model assessment IR (HOMA IR), HOMA S and HOMA beta were calculated
      for the assessment of IR, insulin sensitivity and pancreatic beta cell function.
      RESULTS: At three months follow-up, plasma ghrelin levels and HOMA IR in CPAP
      group were significantly decreased (P=0.002 and 0.046, respectively) while those
      in control group increased significantly (P=0.012 and 0.009, respectively).
      Significant moderate correlations were found between ghrelin vs. HOMA IR and
      ghrelin vs. HOMA S after CPAP, however, for those without CPAP, no significant
      associations were observed. CONCLUSIONS: Short-term effective continuous positive
      airway pressure had a significant effect on lowering plasma ghrelin levels and
      IR, but not body fat. Further large scale and longer term studies are warranted
      to corroborate these findings.

PMID- 24033957
TI  - Pressure therapy upregulates matrix metalloproteinase expression and
      downregulates collagen expression in hypertrophic scar tissue.
AB  - BACKGROUND: Pressure therapy improves hypertrophic scar healing, but the
      mechanisms for this process are not well understood. We sought to investigate the
      differential expression of matrix metalloproteinases (Mmps) and collagen in
      posttraumatic hypertrophic scar tissue with mechanical pressure and delineate the
      molecular mechanisms of pressure therapy for hypertrophic scars. METHODS:
      Fibroblast lines of normal skin and scar tissue were established and a mechanical
      pressure system was devised to simulate pressure therapy. Reverse transcription
      polymerase chain reaction (RT-PCR) and Western blotting assays were used to
      compare differences in the mRNA and protein expression of Mmps and collagen in
      scar fibroblasts before and after pressure therapy. RESULTS: The expression
      differed between the hypertrophic scar cell line and the normal cell line. RT-PCR
      assays showed that Collagen I, highly expressed in the hypertrophic scar cell
      line, decreased significantly after pressure therapy. Mmp2, Mmp9, and Mmp12
      expression in the hypertrophic scar tissue increased significantly after pressure
      therapy (P < 0.05). Western blotting assays further revealed that Mmp9 and Mmp12
      expression increased significantly in the hypertrophic scar tissue after pressure
      therapy (P < 0.05) but not Mmp2 expression (P > 0.05). CONCLUSION: Mechanical
      pressure induces degradation of Collagen I in hypertrophic scar tissue by
      affecting the expression of Mmp9 and Mmp12.

PMID- 24033958
TI  - Clinical analysis of laparoscopic surgery for ovarian masses under different
      conditions during the second trimester.
AB  - BACKGROUND: Laparoscopic surgery in pregnant women has become increasingly more
      common; however, the safety of laparoscopy in this population has been widely
      debated in emergent situations and big size at bigger pregnant weeks. This study
      was to determine the characteristics of laparoscopic surgery for adnexal masses
      in different conditions during the second trimester of pregnancy. METHODS:
      Between April 2002 and December 2011, 24 patients with suspected ovary cyst
      during the second trimester underwent laparoscopic surgery at the Peking Union
      Medical College Hospital retrospectively. Clinical data were collected
      retrospectively and patient's outcomes were analyzed. RESULTS: The incidence of
      laparoscopic surgery for ovarian cysts during pregnancy was 0.12% of all
      laparoscopic gynecological surgeries performed at the hospital. No patients
      required conversion. There were 9 (37.5%) patients whose gestational age was no
      less than 16 weeks, and 15 patients whose gestational age was less than 16 weeks;
      no difference was noted in the operation time between the two groups (P > 0.05).
      Emergency surgery due to abdominal pain was performed in 4 (16.7%) patients, 2
      (8.3%) of whom underwent simple salpingo-oophorectomy because of ovarian
      necrosis. The other patients underwent enucleation of the ovarian cyst. There
      were no severe complications. Twenty (83.3%) pregnant women delivered healthy
      term infants and 4 (16.7%) cases were lost to follow up. CONCLUSION: Laparoscopic
      surgery for ovary masses is a safe and feasible procedure for the treatment of
      ovary cyst in different conditions during the second trimester, even if
      gestational age reaching 16-19 weeks or in emergency.

PMID- 24033959
TI  - Preliminary exploration of the development of a collagenous artificial dura mater
      for sustained antibiotic release.
AB  - BACKGROUND: Intracranial infection is one of the most common complications of
      open craniocerebral injury and of conventional craniotomy in neurosurgery. The
      presence of blood-brain barrier leads to lower drug concentrations in the
      cerebrospinal fluid than in the venous blood. Increasing the intravenous dosage
      or frequency carries the risk of systemic adverse reactions or infections in
      other parts of the body. Developing an artificial dura mater (ADM) for sustained
      antibiotic release for use during neurosurgery can solve the problems perfectly.
      METHODS: Three types of drug-loaded ADMs made of collagen and containing
      cefuroxime sodium, ceftriaxone sodium, or norvancomycin were prepared. The
      antibacterial activity and sustained release characteristics of the ADMs were
      examined using bacteriostatic and release tests. RESULTS: Single-layered collagen
      based ADMs (40 mm*50 mm*5 mm) containing 18 mg cefuroxime sodium or ceftriaxone
      sodium were not suitable for continued development because of drug preservation
      and stability issues. Using smaller ADMs (20 mm*30 mm*7 mm), containing 4.86 mg
      of norvancomycin, with increased collagen density and a three-layered film with
      two outer drug-free films above and below the antibiotic layer resulted in
      sustained cumulative release of 2.91 mg (59.9%) of norvancomycin over 72 hours.
      The similar factor (f2) comparison method proved that products from a same batch
      were statistically significant similar (f2 > 50). CONCLUSIONS: Artificial ADMs
      made of collagen can be processed to provide a mature dural repair material for
      the sustained release of norvancomycin. This system may provide a basis for
      developing sustained release materials for other drugs.

PMID- 24033960
TI  - Effect of artificial colloids on blood coagulation during shock stage of severe
      burn injury.
AB  - BACKGROUND: There are controversies about the use of artificial colloids. This
      research was aimed to determine the effect of various artificial colloids on
      blood coagulation in the shock stage of severe burn injury. METHODS: Totally, 18
      female Ba-Ma mini-pigs were subjected to a 40% total body surface third-degree
      flame burn under anesthesia. Resuscitation therapy was applied 2 hours after the
      injury, using the burn shock fluid resuscitation formula commonly accepted in the
      surgical treatment of burns. The Ba-Ma mini-pigs were randomly assigned to three
      groups (six pigs in each group): succinylated gelatin group (the artificial
      colloid used was succinylated gelatin Injection), hydroxyethyl starch group (the
      artificial colloid used was hydroxyethyl starch (130/0.4)), and allogeneic plasma
      group (the colloid used was allogeneic plasma). Blood samples were collected from
      the animals prior to the burn injury and again at intervals of 4, 8, 24 and 48
      hours post-injury. The platelet count (PLT), prothrombin time (PT), international
      normalized ratio (INR), activated partial thromboplastin time (APTT), and
      fibrinogen (Fib) were measured, followed by a statistical analysis of all
      results. RESULTS: The PLT of succinylated gelatin group and hydroxyethyl starch
      group at intervals of 24 and 48 hours were (124.3 +/- 52.7), (78.8 +/- 16.4) *
      10(9)/L and (159.0 +/- 62.8), (87.3 +/- 32.0)* 10(9)/L respectively. But in the
      allogeneic plasma group at intervals of 8, 24, and 48 hours were (234.3 +/-
      52.6), (136.0 +/- 47.4), (75.8 +/- 31.0) * 10(9)/L. The decrease were all
      statistically significant (P < 0.05, P < 0.01) when compared to pre-burn ((383.3
      +/- 77.9), (382.7 +/- 65.7), (381.0 +/- 49.4)* 10(9)/L). The PLT among the three
      groups, at all the time points, had no statistical difference (P > 0.05).
      Compared to pre-burn ((10.8 +/- 0.9), (11.4 +/- 0.8), (10.6 +/- 0.7) seconds),
      the PT of succinylated gelatin group and hydroxyethyl starch group at 24 hours
      were (14.5 +/- 1.5) and (16.2 +/- 1.3) seconds, whereas in the allogeneic plasma
      group at 8 and 24 hours the PT were (13.0 +/- 0.9) and (14.5 +/- 1.5) seconds,
      i.e., an increase in the statistical significance (P > 0.01). Statistical
      significance was observed at 8 and 48 hours between the succinylated gelatin
      group and hydroxyethyl starch group, and at 48 hours between the hydroxyethyl
      starch and allogeneic plasma group (P < 0.05). The INR at 24 hours were (1.26 +/-
      0.13) in the succinylated gelatin group, (1.40 +/- 0.11) in the hydroxyethyl
      starch group, and (1.13 +/- 0.07) and (1.26 +/- 0.13) at 8 and 24 hours in the
      allogeneic plasma group. When compared with pre-burn ((0.94 +/- 0.08), (0.99 +/-
      0.07), and (0.92 +/- 0.06) seconds), the other groups have increased
      significantly (P > 0.01). The comparison at 8 and 48 hours between the
      succinylated gelatin group and the hydroxyethyl starch group, at 48 hours between
      hydroxyethyl starch group and allogeneic plasma group showed statistical
      difference (P < 0.01). The APTT of succinylated gelatin group and hydroxyethyl
      starch group at 24 hours were (13.1 +/- 1.1) and (14.6 +/- 2.9) seconds. The APTT
      of the allogeneic plasma group at 4, 8 and 24 hours were (10.9 +/- 1.4), (11.8 +/
      1.1), and (13.7 +/- 1.5) seconds. Compared to pre-burn ((11.5 +/- 4.2), (11.2 +/
      3.3), (10.1 +/- 1.4) seconds), they were statistically significant (P < 0.05).
      There was no statistical difference in the APTT between the three groups, at all
      the time points. The Fib of the succinylated gelatin group at 24 and 48 hours
      were (4.3 +/- 0.3) and (4.7 +/- 0.2) g/L, (4.1 +/- 0.3), and (5.0 +/- 0.1) g/L in
      allogeneic plasma group, and at 8, 24, and 48 hours the Fib for the hydroxyethyl
      starch group was (2.9 +/- 0.4), (4.0 +/- 0.5), and (4.6 +/- 0.6) g/L. Compared to
      pre-burn ((2.4 +/- 0.2), (2.5 +/- 0.3), (2.6 +/- 0.5) g/L), they were all
      statistically significant (P < 0.01). There was no statistical difference in APTT
      between the three groups, at all time points. CONCLUSION: The changes of the
      indices in blood coagulation during the shock phase of a severe burn injury
      correlate with the stress response to the burn, rather than to the application of
      HES (130/0.4) and succinylated gelatin.

PMID- 24033961
TI  - Analysis of transforming growth factor beta signaling in chronic rhinosinusitis.
AB  - BACKGROUND: It has been reported that there is a significant difference in the
      local tissue concentration of transforming growth factor (TGF)-beta1 between
      chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis
      without nasal polyps (CRSwNP) patients. TGF-beta has been reported to play an
      important role in regulating epithelial cell repair in lower airway remodeling
      and may be a critical factor involved in the remodeling process of chronic
      rhinosinusitis (CRS). METHODS: Ethmoidal mucosal samples collected from CRS and
      healthy control patients were analyzed for TGF-beta1, TGF-beta receptor I, TGF
      beta receptor II, Smad3, phospho-Smad3, Smad7, and Smad anchor for receptor
      activation by Western blotting analysis. The proliferation of sinonasal
      epithelial cells at baseline and after TGF-beta1 and/or EGF stimulation was
      evaluated by the MTT assay. RESULTS: In CRSsNP, TGF-beta1, TGF-beta receptor I,
      TGF-beta receptor II, and Smad3 protein levels were significantly higher than
      controls. In CRSwNP, TGF-beta1, Smad3, and pSmad3 protein levels were
      significantly lower than controls. Smad7 protein was significantly higher in CRS
      than controls. In vitro experiments demonstrated that the baseline proliferation
      levels of sinonasal epithelial cells were lower in CRS than controls.
      CONCLUSIONS: CRSwNP is characterized by a lower level of TGF-signaling compared
      with the control. In CRSsNP, although the upstream signaling of TGF-beta was
      enhanced, the high Smad7 protein expression may restrain the downstream signaling
      components (e.g., pSmad3) and the TGF-beta antiproliferative effect on sinonasal
      epithelium. The difference in the local tissue concentration of TGF-beta1 between
      CRSsNP and CRSwNP patients did not result in significant differences in
      epithelial proliferation.

PMID- 24033962
TI  - Establishment of a novel method for primary culture of normal human cervical
      keratinocytes.
AB  - BACKGROUND: Cervical keratinocytes are recovered at a low numbers and frequently
      associated with contaminating human fibroblasts which rapidly overgrow the
      epithelial cells in culture with medium supplemented with 10% fetal bovine serum
      (FBS). However, it is difficult to initiate keratinocyte cultures with serum-free
      keratinocyte growth medium alone because cell attachment can be poor. Therefore,
      the culture of these cells is extremely difficult. In this study, we described a
      modified culture medium and coated culture plastics for growing normal human
      cervical epithelial cells in vitro. METHODS: Normal cervical epithelial tissue
      pieces were obtained and digested with type I collagenase to dissociate the cells
      and a single cell suspension produced. The cells were cultured on plastic tissue
      culture substrate alone or substrate coated with collagen type I from rat tail,
      with modified keratinocyte serum-free medium (K-SFM) supplemented with 5% FBS.
      After attachment, the medium were replaced with K-SFM without FBS. The expression
      of basal keratins of the ectocervical epithelium, K5, K14 and K19 were assayed by
      immunofluorescence with monoclonal antibodies to identify the cell purity.
      RESULTS: Our results indicate that cells attached to the culture plastic more
      quickly in K-SFM supplemented with 5% FBS than in K-SFM alone, as well as to
      tissue culture plastic coated with collagen type I than plastic alone. The
      modified medium composed of K-SFM and 5% FBS combined with a specific tissue
      culture plastic coated with collagen type I from rat tail was the best method for
      culture of normal cervical epithelial cells. K5, K14 and K19 were assayed and
      keratinocyte purity was nearly 100%. CONCLUSION: A novel, simple and effective
      method can be used to rapidly obtain highly purified keratinocytes from normal
      human cervical epithelium.

PMID- 24033963
TI  - Chemotherapy with or without gefitinib in patients with advanced non-small-cell
      lung cancer: a meta-analysis of 6,844 patients.
AB  - BACKGROUND: Gefitinib is widely used in patients with advanced non-small-cell
      lung cancer (NSCLC), in whom chemotherapy had failed. Previous trials reported
      inconsistent findings regarding the efficacy of gefitinib on overall survival
      (OS) and progression free survival (PFS). This study was to evaluate the effects
      of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients
      with NSCLC. METHODS: We systematically searched Medline, EmBase, the Cochrane
      Central Register of Controlled Trials, reference lists of articles, and
      proceedings of major meetings for relevant literature. Randomized controlled
      trials (RCTs) comparing chemotherapy with and without gefitinib in the treatment
      of patients with advanced NSCLC were included in our analysis. The primary
      endpoints were OS and PFS. RESULTS: Of 182 relevant studies, 12 were included in
      the final analysis, which consisted of 6844 patients with NSCLC. Overall, we
      noted that gefitinib therapy had an 8% improvement in the OS as compared to the
      gefitinib-free therapy, but this difference was not statistically significant
      (HR, 0.92; 95% CI: 0.85-1.00; P=0.051). Furthermore, gefitinib therapy had
      significantly longer PFS compared to gefitinib-free therapy (HR, 0.72; 95% CI
      0.60-0.87, P=0.001). Patients receiving gefitinib therapy also had a more
      frequent objective response rate (ORR) than the control arm (OR, 2.51; 95% CI,
      1.67-3.78, P < 0.001). Rashes, diarrhea, dry skin, pruritus, paronychia, and
      abnormal hepatic function were more frequent in the gefitinib therapy group.
      CONCLUSIONS: Treatment with gefitinib had a clear effect on PFS and ORR, and it
      might contribute considerably to the OS. Furthermore, there was some evidence of
      benefit for gefitinib therapy among patients with adenocarcinoma.

PMID- 24033964
TI  - Vitamin D status and the risk of pancreatic cancer: a meta-analysis.
AB  - BACKGROUND: Vitamin D status in relation to pancreatic cancer risks is still
      inconsistent. This study was performed to evaluate the association between
      vitamin D status and risk of pancreatic cancer using a meta-analysis approach.
      METHODS: A systemic review of all relevant literature in English was performed by
      searching Pubmed, Web of Science and Embase to identify eligible studies from the
      earliest available date to April 1, 2012. The search terms "vitamin D", "25
      hydroxyvitamin D", "pancreatic cancer" or "pancreatic neoplasms" were used to
      retrieve relevant papers. Inclusion criteria were: (1) the exposure of interest
      was intake of vitamin D or blood levels of vitamin D; (2) the outcome of interest
      was pancreatic cancer; (3) data on high and low intake or blood vitamin D in
      cases and controls were available; (4) odds ratio (OR) estimates with 95%
      confidence interval (CI) were provided; (5) primary epidemiological data were
      provided reporting pancreatic cancer incidence. The combined OR values and their
      95% CIs were calculated via a meta-analysis. The potential presence of
      publication bias was estimated using Egger's regression asymmetry test. RESULTS:
      Nine studies with a total of 1 206 011 participants met the inclusion criteria.
      The test for heterogeneity showed there were significant differences among the
      included studies (I(2)=70.9%, P=0.001), so a randomized-effects model was used in
      the meta-analysis. The pooled OR of pancreatic cancer for the highest versus the
      lowest categories of vitamin D level was 1.14 (95% CI 0.896-1.451), and the Z
      score for the overall effect was 1.06 (P=0.288), showing that there was no
      significant association between vitamin D levels and the risk of pancreatic
      cancer. Egger's test indicated there was a low possibility of publication bias in
      this study (P=0.348). CONCLUSION: Dietary vitamin D or circulating concentrations
      of 25-hydroxyvitamin D are not associated with the risk of pancreatic cancer
      based on evidence from currently published studies.

PMID- 24033965
TI  - Interleukin-18 promoter gene -607C/A polymorphism and tuberculosis risk: a meta
      analysis.
AB  - BACKGROUND: Numerous studies have evaluated the association between interleukin
      18 (IL-18) promoter gene -607C/ A (rs1946518) polymorphism and tuberculosis (TB)
      risk. However, the results remain apparently conflicting. The aim of this study
      was to investigate whether IL-18-607C/A polymorphism is associated with
      susceptibility to TB. METHODS: Publications addressing the association between
      the IL-18-607C/A polymorphism and TB risk were selected from the Pubmed, Cochrane
      Library, Embase, CNKI and Wanfang databases. Data were extracted from the studies
      by two independent reviewers. Statistical analysis was performed using RevMan
      5.0.25 and STATA 11.0 software. RESULTS: Eight case-control studies with a total
      of 1166 TB patients and 1734 controls were retrieved. Meta-analysis results
      showed significant association between IL-18-607C/A polymorphism and TB risk in
      all comparisons of the A allele versus C allele (OR=1.17, 95% CI 1.05-1.30,
      P=0.004), AA versus CC (OR=1.43, 95% CI 1.14-1.81, P=0.002), CA+AA versus CC
      (OR=1.20, 95% CI 1.01-1.42, P=0.04) and AA versus CA+CC (OR=1.30, 95% CI 1.07
      1.58, P=0.007). In subgroup analysis by nationality, a significant association
      between IL-18-607C/A polymorphism and TB risk in the comparisons of A versus C,
      CA+AA versus CC and AA versus CA+CC (OR=1.22, 95% CI 1.07-1.38, P=0.002; OR=1.31,
      95% CI 1.06-1.61, P=0.01; OR=1.32, 95% CI 1.07-1.63, P=0.01, respectively) were
      found in Chinese population but not in Indian and Iranian populations.
      CONCLUSION: This study suggests that the -607C/A polymorphism of IL-18 gene would
      be a risk factor for TB, especially in Chinese population. To further evaluate
      gene-to-gene and gene-to-environment interactions on -607C/A polymorphism and
      tuberculosis risk, more studies with thousands of patients are required.

PMID- 24033966
TI  - Brain stimulation for treatment of refractory epilepsy.
AB  - OBJECTIVE: We review the targets of the deep brain and the responsive
      neurostimulation system (RNS) to identify the best optimal stimulation parameters
      and the best mode of stimulation, whether cyclical, continuous, or smarter. DATA
      SOURCES: This review is based on data obtained from published articles from 1950
      to 2013. To perform the PubMed literature search, the following keywords were
      input: deep brain stimulation (DBS), RNS, and refractory epilepsy. STUDY
      SELECTION: Articles containing information related to brain stimulation or RNS
      for the treatment of refractory epilepsy were selected. RESULTS: The currently
      available treatment options for those patients who resist multiple antiepileptic
      medications and surgical procedures include electric stimulation, both direct and
      indirect, of brain nuclei thought to be involved in epileptogenesis. The number
      of potential targets has increased over the years to include the anterior nucleus
      of the thalamus, the centromedian nucleus of the thalamus, the hippocampus, the
      subthalamic nucleus, the caudate nucleus, and the cerebellum, among others. The
      results of a randomized controlled trial and the RNS trial were published to
      reveal the effectiveness. CONCLUSIONS: Although statistically significant
      reductions in seizures have been observed using several different stimulation
      techniques, including vagus nerve stimulation, DBS, and RNS, these effects are
      currently only palliative and do not approach the efficacy comparable with that
      seen in resection in appropriately selected patients. More research is needed to
      determine optimal stimulation targets and techniques as well as to determine
      which epilepsy patients will benefit most from this technology.

PMID- 24033967
TI  - Role of CXCL12/CXCR4 signaling axis in pancreatic cancer.
AB  - OBJECTIVE: This review focuses on the state-of-the-art of CXCL12/CXCR4 signaling
      axis in pancreatic cancer and its role in tumor progression. DATA SOURCES:
      Relevant articles published in English were identified by searching in Pubmed
      from 1997 to 2013, with keywords "CXCL12", "CXCR4" and "pancreatic cancer".
      Important references from selected articles were also retrieved. STUDY SELECTION:
      Articles about CXCL12/CXCR4 signaling axis in pancreatic cancer and relevant
      mechanisms were selected. RESULTS: Pancreatic cancer has been one of the most
      lethal human malignancies, with median survival less than one year and overall 5
      year survival only 6%. Tumor cells from pancreatic cancer express high level of
      CXCR4. CXCL12, the ligand for CXCR4, is extensively secreted by neighboring
      stromal cells and other distant organs. CXCL12 primarily binds to CXCR4, induces
      intracellular signaling through several divergent pathways, which are involved in
      progression and metastasis of pancreatic cancer. CONCLUSIONS: CXCL12/CXCR4
      signaling axis may play an important role in the communication between pancreatic
      cancer cells and their microenvironment, which may have effect on tumor
      proliferation, invasion, angiogenesis, metastasis and chemoresistance.
      CXCL12/CXCR4 signaling axis may serves as a novel therapeutic target for
      pancreatic cancer.

PMID- 24033968
TI  - Bronchial thermoplasty.

PMID- 24033969
TI  - Albumin for fluid resuscitation in patients with sepsis: what do we expect for?

PMID- 24033970
TI  - Unique association of adiponectin isoforms with serum cytokines and redox
      molecules in patients with chronic obstructive pulmonary disease.

PMID- 24033971
TI  - Experience and early outcome of treating retrograde type A dissection with
      primary entry tear in the descending thoracic aorta.

PMID- 24033972
TI  - New ideas for the diagnosis and treatment of Fanconi syndrome: a pilot study.

PMID- 24033973
TI  - Sarcomatoid malignant pleural mesothelioma confirmed by full-thickness biopsy.

PMID- 24033974
TI  - Successful management of incarcerated Morgagni's diaphragmatic hernia in a 62
      year-old man.

PMID- 24033975
TI  - Spotlight on inflammatory reaction in acute myocardial infarction combined with
      acute myeloid leukemia.

PMID- 24033976
TI  - Sufentanil induced muscle rigidity identified by ventilator graphics in medical
      intensive care unit.

PMID- 24033977
TI  - Serum CA125 changes in one case with malignant transformation from benign
      endometriosis to Mullerian adenosarcoma.

PMID- 24033978
TI  - Targetoid hemosiderotic hemangioma (Hobnail Hemangioma): typical clinical and
      histological presentation.

PMID- 24033979
TI  - Successful application of a novel dressing for the treatment of ulcerative
      cutaneous sarcoidosis.

PMID- 24033981
TI  - Modulation by essential oil of vaccine response and production improvement in
      chicken challenged with velogenic Newcastle disease virus.
AB  - AIM: To evaluate the impact of Eucalyptus and peppermint essential oils on immune
      modulation and production of broiler chicken challenged with a molecularly
      characterized velogenic NewCastle disease virus (vNDV). METHODS AND RESULTS: The
      experimental design included five treatments with three replicate pens/treatment
      comprised of 12-day-old broilers chicks/replicate. The five treatments included a
      positive challenge control (non-NDV vaccinated/nonessential oil
      treated/challenged) (NNEOC), a negative challenge control (NDV
      vaccinated/essential oil treated/unchallenged) (VEOU), a non-NDV
      vaccinated/essential oil treated/challenged (NEOC), a NDV vaccinated/nonessential
      oil treated/challenged (VNEOC) and a NDV vaccinated/essential oil
      treated/challenged (VEOC). The lowest mean survival rate (0.0%) and lowest
      production performance were obtained by the positive challenge control, while the
      best mean survival (93.3%) and average body weight (2649 g) were obtained by the
      negative challenge controls (P < 0.05). Among the three others challenged
      treatments, the best mean survival (79.2%), highest mean body weight at 42 days
      of age (2445 g), the lowest feed conversion ratio (1.60) and the highest serum
      conversion immunopotentiation at 35 days of age determined by ELISA and
      hemagglutination titres were obtained by the VEOC birds compared with respective
      means obtained by birds of the NEOC and VNEOC treatments (P < 0.05). CONCLUSIONS:
      The results supported the possibility of using the essential oils of Eucalyptus
      and Peppermint in broilers to immunopotentiate the response to vaccination
      against velogenic NDV, helping in significant improvement of survival and
      production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides information
      about the potential use of essential oils of eucalyptus and peppermint that can
      be exploited as commercial immunopotentiators for the protection of NDV
      vaccinated broiler chickens against economic velogenic NDV.

PMID- 24033982
TI  - Symmetric nodules on both soles in a 4-month-old baby.

PMID- 24033983
TI  - Ambulatory arterial stiffness index: Is there an additional value to characterize
      cardiovascular risk in children with kidney transplant?

PMID- 24033980
TI  - Surface L-type Ca2+ channel expression levels are increased in aged hippocampus.
AB  - Age-related increase in L-type Ca(2+) channel (LTCC) expression in hippocampal
      pyramidal neurons has been hypothesized to underlie the increased Ca(2+) influx
      and subsequent reduced intrinsic neuronal excitability of these neurons that lead
      to age-related cognitive deficits. Here, using specific antibodies against Cav
      1.2 and Cav 1.3 subunits of LTCCs, we systematically re-examined the expression
      of these proteins in the hippocampus from young (3 to 4 month old) and aged (30
      to 32 month old) F344xBN rats. Western blot analysis of the total expression
      levels revealed significant reductions in both Cav 1.2 and Cav 1.3 subunits from
      all three major hippocampal regions of aged rats. Despite the decreases in total
      expression levels, surface biotinylation experiments revealed significantly
      higher proportion of expression on the plasma membrane of Cav 1.2 in the CA1 and
      CA3 regions and of Cav 1.3 in the CA3 region from aged rats. Furthermore, the
      surface biotinylation results were supported by immunohistochemical analysis that
      revealed significant increases in Cav 1.2 immunoreactivity in the CA1 and CA3
      regions of aged hippocampal pyramidal neurons. In addition, we found a
      significant increase in the level of phosphorylated Cav 1.2 on the plasma
      membrane in the dentate gyrus of aged rats. Taken together, our present findings
      strongly suggest that age-related cognitive deficits cannot be attributed to a
      global change in L-type channel expression nor to the level of phosphorylation of
      Cav 1.2 on the plasma membrane of hippocampal neurons. Rather, increased
      expression and density of LTCCs on the plasma membrane may underlie the age
      related increase in L-type Ca(2+) channel activity in CA1 pyramidal neurons. 

PMID- 24033984
TI  - Molecular characterization of Listeria monocytogenes isolated from fresh seafood
      samples in Iran.
AB  - BACKGROUND: Among all species of Listeria, Listeria monocytogenes (L.
      monocytogenes) is a major pathogenic microorganism of humans and animals and L.
      ivanovii is rarely pathogenic for humans. The objective of this study was to
      isolate and characterize Listeria species and to determine the frequencies of
      virulence genes in L. monocytogenes serotypes in fresh fish, shrimp, crab and
      lobster in Isfahan and Shahrekord, Iran. METHODS: From September 2010 to April
      2011, a total of 300 marine food samples were purchased from supermarkets of
      Isfahan and Shahrekord cities, Iran. All samples were cultured and the positive
      samples for L. monocytogenes were analyzed for presence of serotypes and
      virulence genes. RESULTS: From the total 300 samples, 23 (10.45%) fresh fish and
      1 (2.5%) shrimp samples were positive for Listeria spp., but there were no
      positive lobster and crab samples for Listeria species. Only L. monocytogenes was
      isolated from 17 fish (7.25%) and 1 shrimp (2.5%) samples while L. innocua, L.
      ivanovii and L. seeligeri only detected in fish samples (2 (0.9%), 3 (1.36%) and
      1 (0.45%)), respectively. The plcA, prfA, actA, hlyA and iap virulence genes were
      detected in all of the 18 L. monocytogenes isolates. Totally, the 4b, 1/2a and
      1/2b serotypes were detected in 66.66%, 5.55% and 27.77% bacterial isolates,
      respectively. CONCLUSIONS: Consumption of these sea foods, either raw or
      undercooked, may contribute to food-borne illness due to L. monocytogenes in
      Iran. The hygienic quality of sea food products should be observe. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3422944359800606.

PMID- 24033985
TI  - Randomized controlled trial comparing efficacy between a vaginal misoprostol
      loading and non-loading dose regimen for second-trimester pregnancy termination.
AB  - AIM: The aim of this study was to compare the efficacy of vaginal misoprostol
      loading dose regimen with non-loading dose regimen for termination of second
      trimester pregnancy with live fetuses. MATERIAL AND METHODS: A randomized
      controlled trial was conducted on pregnant women with a live fetus at 14-28
      weeks. The patients were randomly allocated to receive either the vaginal
      misoprostol loading dose regimen (600 mcg, then 400 mcg every 6 h) or the non
      loading dose regimen (400 mcg every 6 h). Failure to abort within 48 h was
      considered to be a failure. RESULTS: Of 157 recruited women, 77 were assigned to
      be in group 1 (loading group) and 80 were in group 2 (non-loading group). The
      median abortion time was not statistically different between the groups (14.08;
      95% confidence interval: 12.45-17.77 h and 14.58; 95% confidence interval: 12.8
      17.27 h, P > 0.05). The rates of abortion within 24 h and 48 h were also
      comparable between the groups. Fever and chills were more common in the loading
      group. No other serious complications, such as postpartum hemorrhage and uterine
      rupture, were found. CONCLUSION: Vaginal misoprostol in the loading dose regimen
      had a similar efficacy to the non-loading dose regimen but was associated with
      more adverse maternal effects.

PMID- 24033986
TI  - Retinal degeneration and persistent serous detachment in the absence of active
      choroidal neovascularization in pseudoxanthoma elasticum.

PMID- 24033987
TI  - Human cumulative culture: a comparative perspective.
AB  - Many animals exhibit social learning and behavioural traditions, but human
      culture exhibits unparalleled complexity and diversity, and is unambiguously
      cumulative in character. These similarities and differences have spawned a debate
      over whether animal traditions and human culture are reliant on homologous or
      analogous psychological processes. Human cumulative culture combines high
      fidelity transmission of cultural knowledge with beneficial modifications to
      generate a 'ratcheting' in technological complexity, leading to the development
      of traits far more complex than one individual could invent alone. Claims have
      been made for cumulative culture in several species of animals, including
      chimpanzees, orangutans and New Caledonian crows, but these remain contentious.
      Whilst initial work on the topic of cumulative culture was largely theoretical,
      employing mathematical methods developed by population biologists, in recent
      years researchers from a wide range of disciplines, including psychology,
      biology, economics, biological anthropology, linguistics and archaeology, have
      turned their attention to the experimental investigation of cumulative culture.
      We review this literature, highlighting advances made in understanding the
      underlying processes of cumulative culture and emphasising areas of agreement and
      disagreement amongst investigators in separate fields.

PMID- 24033988
TI  - The mouse pathology ontology, MPATH; structure and applications.
AB  - BACKGROUND: The capture and use of disease-related anatomic pathology data for
      both model organism phenotyping and human clinical practice requires a relatively
      simple nomenclature and coding system that can be integrated into data collection
      platforms (such as computerized medical record-keeping systems) to enable the
      pathologist to rapidly screen and accurately record observations. The MPATH
      ontology was originally constructed in 2,000 by a committee of pathologists for
      the annotation of rodent histopathology images, but is now widely used for coding
      and analysis of disease and phenotype data for rodents, humans and zebrafish.
      CONSTRUCTION AND CONTENT: MPATH is divided into two main branches describing
      pathological processes and structures based on traditional histopathological
      principles. It does not aim to include definitive diagnoses, which would
      generally be regarded as disease concepts. It contains 888 core pathology terms
      in an almost exclusively is_a hierarchy nine layers deep. Currently, 86% of the
      terms have textual definitions and contain relationships as well as logical
      axioms to other ontologies such the Gene Ontology. APPLICATION AND UTILITY: MPATH
      was originally devised for the annotation of histopathological images from mice
      but is now being used much more widely in the recording of diagnostic and
      phenotypic data from both mice and humans, and in the construction of logical
      definitions for phenotype and disease ontologies. We discuss the use of MPATH to
      generate cross-products with qualifiers derived from a subset of the Phenotype
      and Trait Ontology (PATO) and its application to large-scale high-throughput
      phenotyping studies. MPATH provides a largely species-agnostic ontology for the
      descriptions of anatomic pathology, which can be applied to most amniotes and is
      now finding extensive use in species other than mice. It enables investigators to
      interrogate large datasets at a variety of depths, use semantic analysis to
      identify the relations between diseases in different species and integrate
      pathology data with other data types, such as pharmacogenomics.

PMID- 24033989
TI  - Systematic review of self-expanding stents in the management of benign colorectal
      obstruction.
AB  - AIM: Colorectal obstruction due to benign disease is likely to become more
      prevalent. Self-expanding stents have been shown to be effective in reducing
      morbidity and allowing one-stage resection or improved palliation in colorectal
      cancer. This review assessed the use of self-expanding stents in benign
      colorectal obstruction. METHOD: A systematic review was performed using PubMed,
      Embase and the Cochrane Library. Keywords included: 'benign disease' 'colorectal
      obstruction', 'stent', 'endoprosthesis' and 'prosthesis' Original articles from
      all relevant listings were sourced. These were hand searched for further articles
      of relevance. The main outcome measures assessed were technical and clinical
      success, perforation, reobstruction and stoma avoidance in the bridge to surgery
      population. RESULTS: The search strategy identified 130 articles; the 21 included
      studies yielded a pooled analysis of 122 patients. Diverticulitis was the
      predominant aetiology (66/122, 54%). Technical success was achieved in 115/122
      (94%) and clinical success in 108/120 (87%) patients. Overall, the perforation
      rate was 12% (15/122) and the reobstruction rate was 14% (17/122). A stoma was
      avoided in 48% (23/48) of bridge to surgery patients. Perforation and stoma
      avoidance in the bridge to surgery group were worse with an aetiology of
      diverticulitis. CONCLUSION: Complication rates in stenting for benign colorectal
      obstruction are higher than for malignant obstruction. On the basis of limited
      published evidence, stenting cannot be recommended for benign colorectal
      obstruction.

PMID- 24033990
TI  - Atlas-based analysis of cardiac shape and function: correction of regional shape
      bias due to imaging protocol for population studies.
AB  - BACKGROUND: Cardiovascular imaging studies generate a wealth of data which is
      typically used only for individual study endpoints. By pooling data from multiple
      sources, quantitative comparisons can be made of regional wall motion
      abnormalities between different cohorts, enabling reuse of valuable data. Atlas
      based analysis provides precise quantification of shape and motion differences
      between disease groups and normal subjects. However, subtle shape differences may
      arise due to differences in imaging protocol between studies. METHODS: A
      mathematical model describing regional wall motion and shape was used to
      establish a coordinate system registered to the cardiac anatomy. The atlas was
      applied to data contributed to the Cardiac Atlas Project from two independent
      studies which used different imaging protocols: steady state free precession
      (SSFP) and gradient recalled echo (GRE) cardiovascular magnetic resonance (CMR).
      Shape bias due to imaging protocol was corrected using an atlas-based
      transformation which was generated from a set of 46 volunteers who were imaged
      with both protocols. RESULTS: Shape bias between GRE and SSFP was regionally
      variable, and was effectively removed using the atlas-based transformation.
      Global mass and volume bias was also corrected by this method. Regional shape
      differences between cohorts were more statistically significant after removing
      regional artifacts due to imaging protocol bias. CONCLUSIONS: Bias arising from
      imaging protocol can be both global and regional in nature, and is effectively
      corrected using an atlas-based transformation, enabling direct comparison of
      regional wall motion abnormalities between cohorts acquired in separate studies.

PMID- 24033992
TI  - [In Process Citation].

PMID- 24033991
TI  - Induction of cardiac allograft tolerance across a full MHC barrier in miniature
      swine by donor kidney cotransplantation.
AB  - We have previously shown that tolerance of kidney allografts across a full major
      histocompatibility complex (MHC) barrier can be induced in miniature swine by a
      12-day course of high-dose tacrolimus. However, that treatment did not prolong
      survival of heart allografts across the same barrier. We have now tested the
      effect of cotransplanting an allogeneic heart and kidney from the same MHC
      mismatched donor using the same treatment regimen. Heart allografts (n = 3) or
      heart plus kidney allografts (n = 5) were transplanted into MHC-mismatched
      recipients treated with high-dose tacrolimus for 12 days. As expected, all
      isolated heart allografts rejected by postoperative day 40. In contrast, heart
      and kidney allografts survived for >200 days with no evidence of rejection on
      serial cardiac biopsies. Heart/kidney recipients lost donor-specific
      responsiveness in cell-mediated lympholysis and mixed-lymphocyte reaction assays,
      were free of alloantibody and exhibited prolonged survival of donor, but not
      third-party skin grafts. Late (>100 days) removal of the kidney allografts did
      not cause acute rejection of the heart allografts (n = 2) and did not abrogate
      donor-specific unresponsiveness in vitro. While kidney-induced cardiac allograft
      tolerance (KICAT) has previously been demonstrated across a Class I disparity,
      these data demonstrate that this phenomenon can also be observed across the more
      clinically relevant full MHC mismatch. Elucidating the renal element(s)
      responsible for KICAT could provide mechanistic information relevant to the
      induction of tolerance in recipients of isolated heart allografts as well as
      other tolerance-resistant organs.

PMID- 24033994
TI  - The legislation on living organ donation in Western Europe: legal and ethical
      analysis and impact on clinical practice.
AB  - In Europe there are various directives on living organ donation (LOD) that are
      applied differently in member countries. The objectives of this study were as
      follows: (1) to identify the most relevant normative differences among the
      countries of Western Europe, and (2) to evaluate the evolution of LOD data in
      these countries. We performed comparative analysis of national legislations to
      identify the most significant common and different regulatory elements that were
      evaluated subsequently from an ethical-legal point of view. For data analysis on
      LOD, we used the EULOD database of donations in Europe. Relevant legislative
      differences emerged among European countries. Through legal and ethical analysis,
      it has possible to delineate two legal guidelines: on the one hand, based
      primarily on informed consent applying the principle of individual autonomy, and
      on the other hand, informed consent associated with legal and medical criteria.
      From 1992 to 2009, countries with standards based primarily on individual
      informed consent showed an increase in LOD from 5.5% to 25.3%, which was greater
      than those in countries that had additional legal requirements, namely, from 1.6%
      to 16.0.%. The distinct transpositions of the European Directives among singles
      countries related to LOD are based essentially only on the request for informed
      consent or for additional medical and legal requirements. The former practices
      which increases LOD, can facilitate "organ tourism." 

PMID- 24033995
TI  - Organ donation awareness project for Piedmont high school students.
AB  - FOREWORD: Law no. 91 of April 1, 1999 confirmed the principle of citizens' free
      choice and awareness with regards the donation of their own organs and tissue.
      Many studies have shown that information/communication programs aimed at
      secondary school students are able to significantly increase their propensity
      toward donation. Students who are made more aware of the topics of donation and
      transplantation are, in turn, a means of information for their families and
      acquaintances. METHODS: To be effective, communication must contain both
      cognitive and emotional elements. This is the principle underlying the
      development of an awareness-building project that involves the viewing of a play
      "Two of Hearts"-telling the story of a transplant patient, followed by a brief
      scientific presentation aimed at clarifying the basic concepts of transplantation
      medicine, and then an open discussion between the students and experts. This
      initiative was promoted by the Piedmont Regional Tissue and Organ Procurement
      Coordination Agency, the Communication Office of the Piedmont Region, and the
      Regional Education Office for Piedmont. RESULTS: Seven meetings took place in the
      main town of each of the provinces that make up the Piedmont Region. These were
      attended by a total of 1373 students, who were each given an anonymous
      questionnaire. In all, 785 returned the questionnaire; of these, 95% affirmed
      that the contents of the meeting had been clearly presented, and 57% stated that
      they had spoken about it with their family and friends. The project proved be a
      good tool for communicating with young people and, via them, with their families;
      at least 2300 people were reached in this way.

PMID- 24033996
TI  - Organ and tissue donation in migrants: advanced course for cross-cultural
      mediators.
AB  - Between 2004 and 2010 in Piedmont (Italy Northern Region) 1556 brain-death
      situations were reported, including 113 (7.3%) in migrants as potential organ and
      tissue donors. The health staff often has to face migrants, who show great
      cultural differences and language difficulties. The Molinette Hospital Customer
      Care Service, the Piedmont Regional Tissue and Organ Procurement Coordination
      Agency (RPC), and the Cross-Cultural Mediators Association (CMA) organized a
      special course for intercultural mediators, to decrease misunderstandings between
      the health staff and the migrants' families and to improve professional
      communication. In 2011, 28 cultural-linguistic mediators representing different
      groups of migrants in Piemonte took part in a specific course. Over a 5 month
      period they were informed about emotional and communicative aspects, proper to
      the moment of death, as well as organ donation as an intercultural field, the
      professional role of the mediator, the clinical and forensic aspects of brain
      death and donation, and the psychological aspects of organ donation. The course
      was organized by cultural-linguistic mediators of the CMA, the staff of the RPC
      and the teachers at Turin University. The list of the 21 mediators who passed the
      final exam was given to organ and tissue donation hospital co-ordinators in
      Piedmont, so that if necessary, they could obtain the cooperation of these
      qualified people. 

PMID- 24033997
TI  - Hospital health professionals' education about organ and tissue donation: a Turin
      hospital experience.
AB  - The culture of organ and tissue donation is not particularly well established
      among the general population, who often receive incorrect, incomplete
      information. Unfortunately, even among health workers not directly involved in
      the field of transplantation (laypersons), there is a poor level of knowledge
      concerning the underlying principles, mechanisms, and results. To increase lay
      health workers' knowledge and awareness of the importance of donation and
      transplantation, we organized an educational session for (nurses, doctors,
      healthcare workers, technicians, and other professionals) at a hospital
      coordinating service in Turin. The project was divided into 3 phases: first
      (February 2010), we performed an initial survey using an instrument containing 18
      questions. We sought to assess the level of awareness of hospital personnel.
      Among 880 distributed questionnaires, 346 were compiled and returned to the
      authors (39.31%). During the second phase, covering the following 24 months, we
      held 15 educational courses on the subject of transplantation for 483
      participants. In the third and last phase (February 2012), we performed a second
      survey, distributing, 785 questionnaires identical to the previous one, among
      which 404 were compiled and returned (51.46%). 

PMID- 24033998
TI  - Organ donation and transplantation in migrants: Piedmont reality from 2004 to
      2011.
AB  - BACKGROUND: Over the last 20 years, an increasing number of people have
      immigrated into Italy. On January 1, 2011, there were 4,570,317 foreign residents
      in Italy, including 398,910 in the Piedmont region (Italian National Statistics
      Institute data). The Romanian community was the largest, followed by the Moroccan
      and Albanian ones. The numbers are even layer if we consider illegal immigrants.
      As a result, the number of foreign people with brain death has increased, as well
      as the number of foreign people needing organ transplantations. METHODS: The
      Piedmont Regional Coordination Agency of Tissue and Organ Procurement has
      analyzed our 1781 brain death situations between January 2004 and December 2011,
      including 126 (7%) in people not born in Italy (migrants). RESULTS: Non-refusal
      for donation occurred in 79 cases (62.7%). The agency also analyzed each
      community looking at number of brain deaths and non-refusals of donation. We
      utilized 61 donors, for 174 transplantations. Migrants in Italy are not only
      potential tissue and organ donors, but also potential tissue and organ
      recipients. Between 2004 and 2011, 222 patients who had not been born in Italy
      had been transplanted with: a liver (n = 66), a kidney (n = 130), a heart (n =
      21) or a lung (n = 5).

PMID- 24033999
TI  - Living organ donations: a comparison between the positions of national bioethics
      committees.
AB  - Numerous documents have been published by the national bioethics committees of
      the European Union and Council of Europe member countries on the subject of organ
      transplantation. The present paper examines those that address the question of
      living donation with a focus on kidney grafts. Although it is not possible to
      ensure absolute completeness since not all the documents produced over the years
      are accessible and English translations are often lacking, this review covered
      evaluations of the most significant ones. There has been a preponderance of
      attention to the issue of informed consent, while the issue of donor risk has
      been addressed only summarily, if at all. 

PMID- 24034000
TI  - Ethical evaluation of risks related to living donor transplantation programs.
AB  - The shortage of available cadaveric organs for transplantation and the growing
      demand has incresed live donation. To increase the number of transplantations
      from living donors, programs have been implemented to coordinate donations in
      direct or indirect form (cross-over, paired, and domino chain). Living donors
      with complex medical conditions are accepted by several transplantation programs.
      In this way, the number of transplants from living has exceeded that from cadaver
      donors in several European countries. No mortality has been reported in the case
      of lung, pancreas, or intestinal Living donations, but the perioperative
      complications range from 15% to 30% for pancreas and lung donors. In living
      kidney donors, the perioperative mortality is 3 per 10,000. Their frequency of
      end-stage renal disease does not exceed the United States rate for the general
      population. However, long-term follow-up studies of living donors for kidney
      transplantations have several limitations. The frequency of complications in live
      donor liver transplantation is 40%, of these, 48% are possibly life-threatening
      according to the Clavien classification. Residual disability, liver failure, or
      death has occurred in 1% of cases. The changes in live donor acceptance criteria
      raise ethical issues, in particular, the physician's role in evaluating and
      accepting the risks taken by the living donor. Some workers argue to set aside
      medical paternalism on behalf of the principle of donor autonomy. In this way the
      medical rule "primum non nocere" is overcome. Transplantation centers should
      reason beyond the shortage of organs and think in terms of the care for both
      donor and recipient. 

PMID- 24034001
TI  - The concept of self and emotional involvement in living kidney donation: a
      psychometric investigation.
AB  - OBJECTIVE: The aim of our study was to analyze, from a psychological point of
      view, living kidney donor personality, examining a sample of 18 living kidney
      donors. PATIENTS AND METHODS: The personality study was performed using The
      Millon Clinical Multiaxial Inventory-III in 18 potential kidney donors, 6 of whom
      were genetically and 12 emotionally related individuals. RESULTS: Our study
      showed the presence of narcissistic, histrionic, and obsessive-compulsive
      personality traits in living kidney donors. CONCLUSIONS: It is necessary to
      explore the development of motivation for living donation in order to achieve and
      maintain a harmonious relationship with the recipient while respecting their
      individuality.

PMID- 24034002
TI  - Urgent lung transplantation national program: the Italian experience.
AB  - INTRODUCTION: An urgent lung transplantation national program in Italy was
      developed over the past three years. Indispensable conditions that were included
      in the program were invasive respiratory support and/or extracorporeal vascular
      device (DECAP excluded). The aim of this study was to test the effectiveness of
      the program. MATERIALS AND METHODS: We analyzed urgent lung requests received
      between 2009 and 2011 taking into account primary pathology, request outcome,
      average waiting time, and organ origin. Taking as reference the same period of
      time, we also examined the ordinary waiting list, waiting list mortality, and
      number of transplantations performed and we have compared them with another three
      year period prior to the activation of the program. RESULTS: The total number of
      urgent requests was 43. Primary pathologies with the highest incidence proportion
      were cystic fibrosis (40%) and idiopathic pulmonary fibrosis (26.6%). A total of
      34 requests (79%) were successfully dealt with and 9 of them were suspended
      because of worsening conditions. The average waiting time was 17.9 days. During
      the same period of time 340 lung transplantations were performed and there were
      499, 524, and 564 wait-listed patients in 2009, 2010, and 2011, respectively. The
      mortality rate was 21.3%. Over the previous three-year period 295
      transplantations were performed and there were 457, 476, and 464 wait-listed
      patients in 2006, 2007, and 2008, respectively. Also the mortality rate was
      25.3%. DISCUSSION: Urgent lung transplantations can provide patients in an
      imminent life-threatening situation with adequate care without affecting the
      mortality rate of patients on the ordinary waiting list.

PMID- 24034003
TI  - Patients on liver transplantation waiting list with Model for End-Stage Liver
      Disease score >= 30: experience in the Organizzazione Centro Sud Trapianti macro
      area.
AB  - INTRODUCTION: From 2011 a program was developed for liver transplant recipients
      with Model for End-Stage Liver Disease (MELD) score >=30. We examined its
      effectiveness and impact on the other subjects on the waiting list. MATERIALS AND
      METHODS: We analyzed requests received between January 2011 and May 2012 for the
      primary pathology, the outcome, the average waiting time, and the origin of the
      organ. We examined the ordinary waiting list for mortality rates and numbers of
      transplantations over this period (group A) versus a comparable preceding period
      (group B). RESULTS: There were 38 requests for 33 patients. Their primary
      pathologies were cirrhosis associated with viral infection (n = 15), delayed
      graft failure (DGF; n = 5), biliary cirrhosis (n = 4), hepatocellular carcinoma
      (HCC; n = 3 including 2 with cirrhosis), cryptogenic cirrhosis (n = 3),
      postalcoholic cirrhosis (n = 2), metabolic disease (n = 2), and iatrogenic
      disease (n = 1). Of the requests, 25 were successfully dealt with, whereas 5
      requests were temporarily suspended and 2 were permanently suspended because of
      better or worse patient conditions. There were 6 deceased patients. Transplanted
      organs came from the inter-regional area in 64% of cases. The average waiting
      time was 5.9 days. Within group A were a 311 transplantations among 723 waiting
      list patients on with a 13.7% mortality rate. Within group B were 305
      transplantations among 871 wait-listed patients with a 14% mortality rate.
      DISCUSSION: The liver transplantation program for recipients with MELD scores >=
      30 allowed recipients in critical condition to receive grafts without altering
      substantially the opportunities for recipients on the elective waiting list.

PMID- 24034004
TI  - A preliminary European Liver and Intestine Transplant Association-European Liver
      Transplant Registry study on informed recipient consent and extended criteria
      liver donation.
AB  - The European Liver and Intestine Transplant Association (ELITA) and the European
      Liver Transplant Registry (ELTR) coordinated the distribution to European liver
      transplantation centers of an electronic questionnaire, developed by the first
      author, concerning the definition of extended criteria liver donation (ECD) and
      the implication for informed consent of transplant recipients. Completed
      questionnaires were received from 35 centers. All centers accepted ECD liver
      donors. The criteria for defining a liver donor as ECD were as follows: steatosis
      in 33 centers (94%); age up to 80 years in 15 centers (43%); serum sodium >165
      mmol/L in 25 centers (71%); intensive care unit (ICU) stay with ventilation
      longer than 7 days in 17 centers (48%); aspartate aminotransferase (AST) >90 U/L,
      in 6 centers (17%); body mass index (BMI) >30 in 19 centers (54%); alanine
      aminotransferase (ALT) >105 U/L in 8 centers (23%); serum bilirubin >3 mg/dL in
      15 centers (43%); and all criteria together in 2 centers (6%). Thirty-one centers
      informed the transplantation candidate of the ECD status of the donor, 20 (65%)
      when the patient registered for transplantation, 1 (3%) when an ECD liver became
      available, and 10 centers (32%) on both occasions. Thirteen centers required the
      liver transplantation candidate to sign a special consent form. Twenty centers
      informed the potential recipient of the donor's serology. Only 6 centers informed
      the potential recipient of any high-risk behavior of the donor.

PMID- 24034005
TI  - Urgent liver, heart, and lung transplantation programs in Italy: activities and
      evaluation of outcomes.
AB  - The Italian national transplantation network has set up programs for liver,
      heart, and lung transplantation in urgent conditions. The aim of this study was
      to analyze the capability of these programs to meeting needs and their quality.
      In period between 2008 and 2011, the total number of urgent transplant requests
      was analyzed by organ, reason, and outcome, namely waiting time, graft origin,
      and number of transplantations with their one- and three-year graft survivals.
      There were urgent requests for 312 livers, 268 hearts, and 43 lungs totted among
      which 72%, 63%, and 79% were met, respectively. Actuarial graft survival rates at
      one and three years were 62% and 61% for liver and 73.1% and 70.5% for heart
      transplantations, respectively. The rate of satisfied requests and the graft
      outcomes showed that the national urgency programs meet the healthcare needs of
      patients with a short life expectancy, achieving good quality donor-recipient
      match.

PMID- 24034006
TI  - Extracorporeal membrane oxygenation as a bridge to organ donation: a case report.
AB  - Hemodynamic instability is a frequent complication in potential organ donors.
      Despite maximal medical therapy, it can lead to cardiac arrest with consequent
      loss of organs. In this study we present the use of extracorporeal membrane
      oxygenation circulation (ECMO) as a bridge to organ procurement in a potential
      donor with hemodynamic instability. A 14-year-old girl who drowned in a pool
      experienced cardiorespiratory arrest with prolonged resuscitation. In the
      intensive care unit (ICU), she displayed hemodynamic instability requiring high
      doses of inotropis agents. After 60 hours for ICU admission clinical diagnosis of
      brain death, was established and consent for organ donation obtained. During the
      observation period, the hemodynamic instability worsened, requiring ECMO which
      was continued during transport to the operating room and during organ retrieval,
      totaling 3 hours. We retrieved liver, kidneys, heart valves and cornea. Liver and
      kidney transplantations were successfully performed in 3 recipients, all of whom
      displayed appropriate organ functions after 15 months. In conclusion, ECMO
      support of potential donors can be used to prevent cardiac arrest, preserve
      organs, and thus increase the number of potential donors.

PMID- 24034007
TI  - Extracorporeal membrane oxygenation as bridge to lung transplantation.
AB  - Lung transplantation (OLT) is a viable option for end-stage pulmonary diseases in
      selected patients with satisfactory long-term results. However, the paucity of
      available donors engenders a prolonged stay on the waiting list with progressive
      decline of lung function. In cases of sudden respiratory failure, admission to an
      intensive care unit with institution of extracorporeal membrane oxygenation
      (ECMO) may be an option while a waiting an emergency OLT. In 12 OLT candidates we
      started ECMO because of acute decline of lung function. Eleven patients had
      cystic fibrosis and the other subject, histiocytosis X. In 7 patients bilateral
      OLT was performed after a mean waiting time of 6 days from ECMO institution; 5
      patients died on ECMO at a mean time of 11.6 days. After OLT 2 patients required
      reoperation for hemothorax; renal failure and acute leg ischemia occurred in 2
      patients. The mean weaning time from ECMO after OLT was 2.14 days. No patient
      died in the perioperative period and 1-year survival was 85.7%. ECMO represents a
      valid option as a bridge to urgent OLT for selected candidates.

PMID- 24034008
TI  - Ex vivo lung perfusion increases the pool of lung grafts: analysis of its
      potential and real impact on a lung transplant program.
AB  - BACKGROUND: Among the strategies to increase the number of lung transplants, ex
      vivo lung perfusion (EVLP) represents a novel technique to expand the donor pool.
      METHODS: Data from donors referred to our center were retrospectively analyzed to
      identify grafts that could potentially be potentially reconditioned by EVLP and
      for comparison with those obtained by clinical application of EVLP program in our
      center. RESULTS: Among 75 rejected lungs, 23 organs have been identified as
      potentially treatable with EVLP with a hypothetic increase of lung transplant
      activity of 53%. After the introduction of the EVLP program in our center, lung
      transplantation with reconditioned grafts was performed in 7 (23%) patients with
      a 30% increase in transplant procedures. CONCLUSION: Although less than expected,
      EVLP increased the number of lungs suitable for transplantation.

PMID- 24034009
TI  - Initial experience with robot-assisted nephrectomy for living-donor kidney
      transplantation: feasibility and technical notes.
AB  - BACKGROUND: Robot-assisted surgery provide endowrist instruments and 3
      dimensional visualization of the operative field that are improvements over
      traditional laparoscopy. The few research studies published so far have
      demonstrated that living-donor nephrectomy using the robot-assisted technique is
      safe and feasible, providing advantages for patients. METHODS: Since November
      2009, we performed 20 robot-assisted living-donor nephrectomies. Eight patients
      underwent hand-assisted robotic nephrectomy, whereas 20, totally robotic
      nephrectomy. RESULTS: Median intraoperative bleeding was 174 mL (range, 10-750)
      but no patient needed intraoperative transfusion with blood cells. The median
      warm ischemia time was 3.16 minutes (range, 0.30-6.5). there was no case of
      conversion to an open procedure. The median operative time was 311 minutes
      (range, 85-530); the median console time was 160 minutes (range, 135-220).
      CONCLUSION: Robot-assisted living-donor kidney recovery was a safe and effective
      procedure. The totally robotic recovery is an evolving technique. The prospect of
      robotic staplers, endowrist ligature, and robotic single port may further
      increase these advantages.

PMID- 24034010
TI  - Expanding the living donor pool, "Ist Act": analysis of the causes of exclusion
      of potential kidney donors.
AB  - BACKGROUND: The evaluation of a potential living kidney donor (LKD) leads to
      exclusion of at least 50% of candidates. The aim of this study was to analyze the
      reasons for exclusion of potential LKDs referred to our center. METHODS: We
      retrospectively analyzed historic and clinical data of all potential LKDs who
      were evaluated over 7 years from January 2005 to March 2012. Data were obtained
      by review of an electronic database. RESULTS: Among 79 (50 female, 29 male)
      candidates, 24 (30.3%) successfully donated, comprising 22 related and 2
      unrelated donors. We excluded 45 (56.9%), and 10 (12.6%) are actively undergoing
      evaluation. Reasons for exclusion were medical (n = 14; 31%), nonmedical (n = 18;
      40%), positive cross-match (n = l7.7%), pregnancy (n = 2; 4.4%), and other
      reasons (n = 3; 6.6%). Of the 14 donors excluded for medical reasons, 75.8% were
      due to diabetes, cardiovascular disease, hypertension, or obesity and 21.5% to
      inadequate renal function, malignancy, or liver disease. Of the 18 (40%) excluded
      for nonmedical reasons, 6 (33.3%) were because the intended recipient received a
      deceased-donor transplantation before the evaluation could be completed, 5
      (27.7%) because the recipient was no longer a candidate for transplantation, 5
      (27.7%) because of donor withdrawal, and 2 (11.1%) for other reasons.
      CONCLUSIONS: Positive cross-match and deceased-donor transplantation during the
      evaluation process were the 2 most common reasons for LKD exclusion. Evaluation
      of potential LKDs is time consuming, requiring a remarkable amount of human and
      material resources. A dedicated pathway for the diagnostic work-up of LKDs may
      speed- the evaluation process and improve its efficiency, use of ABO-incompatible
      or paired-exchange donations may increase the yield of donor organs.

PMID- 24034011
TI  - Renal transplant in patients with polycystic disease: the Italian experience.
AB  - We analyzed the results of kidney transplantation in autosomal dominent
      polycystic kidney disease (ADPKD) patients in Italy, including 14,305
      transplantations performed from January 2002 to December 2010, including: 12,859
      first single or double kidneys from cadaveric donors (13% polycystic), 172
      combined liver-kidney cases (22% polycystic), and 1,303 living-donor organs (7%
      polycystic). Among the first transplantations (12,008 single, 851 double), with
      follow-ups ranging from 16 to 120 months, polycystic patients demonstrated better
      graft survival compared with other kidney diseases (86% vs 82% at 5 years; P <
      .01); mortality was not different (92% vs 79% at 1 year). A better trend was
      obtained also among combined liver-kidney transplantations in ADPKD. Regarding
      pretransplantation management of polycystic patients, we noticed a conservative
      attitude in 32/35 transplant centers. The main indication for nephrectomy was for
      the lack of abdominal space. Regarding instrumental studies, 86% of centers asked
      for second-level investigations computerized tomography for kidney dimensions.
      Radiologic investigations for vasculocerebral malformations were required in 97%
      of the centers: 74% as a routine and 23% in the presence of familial history of
      cerebral hemorrhage. Polycystic patients are good candidates for kidney
      transplantation with correct management before transplantation.

PMID- 24034012
TI  - Effects of ischemia-reperfusion injury in kidney transplantation: risk factors
      and early and long-term outcomes in a single center.
AB  - INTRODUCTION: Ischemia-reperfusion injury (IRI) causes a high rate of delayed
      graft function (DGF), the most frequent complication in the immediate
      postoperative period after cadaveric donor kidney transplantation. Herein we
      evaluated the impact of donor and recipient characteristics on DGF development in
      terms of the incidence of acute rejection episodes, hospital stay, renal
      function, and long-term graft and patient survivals. MATERIALS AND METHODS:
      Between February 1998 and July 2011, 761 patients underwent cadaveric donor
      kidney transplantations. DGF was defined as the need for dialysis in the first
      week. Patients were subdivided according to initial graft function as immediate
      graft function (IGF) or DGF. RESULTS: DGF observed in 241 patients (31.6%) was
      associated independently with expanded criteria donors, extended cold ischemia
      time, Karpinsky histological score, and prior dialysis duration both univariate
      and multivariate analysis. The incidence of acute rejection episodes was 18.1%
      among the DGF group versus 1.3% in the IGF group (P < .01). DGF significantly
      reduced both graft and patient survivals at 6, 12, 36, and 60 months. CONCLUSION:
      DGF was responsible for a longer hospital stay, worse early and long-term renal
      function, a higher incidence of acute rejection episodes as well as reduced graft
      and patient survivals.

PMID- 24034013
TI  - Influence of cytotoxic T-lymphocyte antigen-4 polymorphisms on acute rejection
      onset of cadaveric renal transplants.
AB  - We retrospectively examined in cadaveric renal transplants the association
      between acute rejection episodes (ARE) and single nucleotide polymorphisms (SNPs)
      localized in the cytotoxic T-lymphocyte antigen (CTLA)-4 promoter, -1147T/C and 
      318C/T, in exon 1 +49A/G and within the 3' untranslated region (UTR) CT60G/A.
      Each one of these SNPs may influence the cell surface expression of the CTLA-4
      molecule. Seventy-two cadaveric renal transplant recipients with at least 6
      month's follow-up were genotyped for CTLA-4 dimorphisms using direct sequencing
      of specific polymerase chain reaction products. Allele frequencies in both groups
      of patients with or without acute rejection (ARE and non-ARE) did not show
      significant differences in various nucleotide positions. At the level of genotype
      frequency we first noted a positive association to acute rejection of G/G
      genotypes (ARE af = 14.7%, non-ARE af = 5.9%) for the +49 (cod. 17), which was
      associated with decreased expression of the CTLA-4 full-length molecule. In
      contrast, the AG genotype seemed to be protective (61.8% vs 32.4%, P = .028; odds
      ratio [OR] = 0.2961). Regarding the CT60G/A dimorphism, noteworthy was the
      identification of a significantly higher incidence of CT60 A/A genotype in ARE
      compared with non-ARE group (29.7% vs 8.6%; Yates P = .035; OR = 4.51). Such
      association of protective AA genotype with ARE, as observed also in autoimmunity,
      was associated with an increased level of sCTLA-4 induced by the polymorphism,
      which blocks B7-flCTLA-4 interactions, enhancing T-cell reactivity by preventing
      transduction of inhibitory signals. Considering the various polymorphic sites in
      the haplotype, we observed a significant increase in ARE among patients of the
      CTLA4 +49A/CT60A (HF = 51.5% vs 29.5%; P = .014; OR = 2.545) and a reduction
      among the +49A/CT60G (17.6% vs 33.8%; P = .04; OR = 0.4193) 2-loci haplotype, As
      regards the -1147/-318/+49/CT60 CTLA-4 4-loci haplotypes, we observed a
      significantly higher frequency of the CCAA haplotype in ARE patients comparison
      with those free of rejection (HF = 51.8% vs 31.1%, P = .046 OR = 2.363). These
      findings are consistent with those observed in allogeneic stem cell
      transplantation, wherein patients with CT60 AA showed a major incidence of graft
      versus-host disease. An association of protective AA genotype with ARE, as
      observed also in autoimmunity was associated with an increased level of sCTLA-4
      induced by this polymorphism, which blocking the B7-flCTLA-4 interaction, would
      enhance T-cell reactivity by preventing transduction of inhibitory signals.

PMID- 24034014
TI  - Advanced age is not an exclusion criterion for kidney transplantation.
AB  - INTRODUCTION: Renal transplantation in patients older than 60 years has long been
      regarded with skepticism owing to the increased risk of complications although,
      as compared with dialysis treatment, a graft seems to improve not only the
      quality of life but also long-term patient survival. This study sought to analyze
      the impact of recipient age older than 60 years on patient and graft outcomes.
      MATERIALS AND METHODS: We retrospectively investigated the outcomes of 761 kidney
      transplant recipients from cadaveric donors performed between February 1998 and
      July 2011. While 69 subjects were at least 60 years of age (group A), 692 were
      younger than 60 years (group B) at the time of transplantation. RESULT: Mean
      follow-up was 60.1 +/- 38.5 months. Delayed graft function (DGF) requiring
      dialysis was observed in 36 group A (52.1%) and 205 group B (29.6%) subjects (P =
      .001). However, there were also significant differences between group A and group
      B in terms of mean donor age (60.3 vs 44.6 years; P < .001) and mean donor
      estimated creatinine clearance (57.8 vs 83.4 mL/min; P < .001). There were no
      significant differences in death-censored graft survival between the two groups,
      but elderly patients experienced worse survival (P = .0005). The most common
      causes of patient death were myocardial infarction, other cardiovascular
      complications, and tumors. CONCLUSION: Kidney transplantation is a good option
      for elderly recipients with end-stage renal disease, providing long graft
      survival and a good quality of life, although these patients are more likely to
      develop cancer or cardiovascular disease. Our findings suggested that older
      patients should not be excluded a priori from transplantation, but meticulous
      screening for cancer and heart disease should be always be performed to improve
      outcomes.

PMID- 24034015
TI  - High nerve growth factor blood concentration in renal transplantation: a new
      prognostic marker?
AB  - BACKGROUND: Nerve growth factor (NGF) belongs to the family of neurotropic
      proteins NGF is markedly expressed in proteinuric renal diseases and in end-stage
      renal disease; it might be involved in kidney physiopathology. To date, little is
      known about NGF concentrations in kidney transplant recipients (KTRs). Because
      NGF exerts its action on cell survival and differentiation, tissue repair, and
      inflammatory responses, it may also be implicated in the pathogenesis of chronic
      allograft nephropathy. The aim of this study was to determine circulating NGF
      concentrations in KTRs and to ascertain their use as a prognostic marker for
      kidney transplant outcomes. METHODS: Using enzyme-linked immunosorbent assay, we
      performed quantification of NGF in the serum of 40 prevalent KTRs at baseline and
      at 6 months. RESULTS: NGF concentrations in KTRs averaged 1.16 +/- 0.67 ng/mL.
      They negative-linearly correlated with recipient age. Logistic multivariate
      regression analysis showed NGF to be independently associated with increased
      proteinuria over the 6-month follow-up. CONCLUSIONS: Our data demonstrated that
      serum concentrations of NGF in KTRs were elevated and that they could be
      considered to be a prognostic marker in kidney transplantation.

PMID- 24034016
TI  - The study of personality in renal transplant patients: possible predictor of an
      adequate social adaptation?
AB  - BACKGROUND: This study explored the personality characteristic traits within a
      sample of renal transplant patients, seeking to obtain predictive index for
      likely clinical impacts. PATIENTS AND METHODS: The personality study was
      performed using the Structured Clinical Interview Axis II Personality Disorders
      for Diagnostic and Statistical Manual of Mental Disorders fourth edition, text
      revision in 60 recipients of kidney transplantations from deceased donors.
      RESULTS: The personality trait that prevailed in the female gender was
      borderline, while in the male gender it appeared to be predominantly obsessive
      compulsive personality trait. CONCLUSIONS: The personality study proved to be a
      good index to predict effects on the level of social adjustment. In this way,
      patients who have shown pathologic personality traits can be identified early to
      provide adequate psychologic-psychiatric support and follow-up.

PMID- 24034017
TI  - The reduction of left ventricular hypertrophy after renal transplantation is not
      influenced by the immunosuppressive regimen.
AB  - BACKGROUND: Cardiovascular (CV) disease is the first cause of death after kidney
      transplantation. Left ventricular hypertrophy (LVH) is one of the main CV risk
      factors. It has been reported that the antiproliferative properties of everolimus
      (EVE) treatment may decrease left ventricular mass. The aim of this study was to
      evaluate the evolution of LVH in two groups of kidney transplant recipients
      receiving immunosuppressive treatment with low-dose calcineurin inhibitor (CNI) +
      EVE or CNI + mycophenolate mofetil (MMF). METHODS: We evaluated 104 patients of
      mean age 47.5 +/- 13.1 years who underwent kidney transplantation between January
      2006 and December 2009 pretransplant by echocardiography, which was repeated
      every year for 3 years during which all patients continued the initial therapy.
      Over the 3-year period 76 subjects were treated with MMF, and 28 with EVE. We
      recorded left ventricular end-diastolic diameter (LVEDD), interventricular septum
      thickness in diastole (IVSTD), left ventricular posterior wall thickness in
      diastole (LVPWD), left ventricular end-diastolic volume and end-systolic volume
      during the follow-up echocardiographic evaluations. RESULTS: No differences in
      the evolution of the echocardiographic parameters were observed between the two
      groups-MMF versus EVE group: LVEDD, 50.3 +/- 5.1 versus 51.2 +/- 6.7 mm; IVSTD,
      11.2 +/- 1.9 versus 11.3 +/- 2 mm; LVPWD, 10.2 +/- 1.9 versus 10.5 +/- 1.7 mm;
      relative wall thickness, 0.041 +/- 0.08 versus 0.42 +/- 0.08; ejection fraction,
      63 +/- 6% versus 61 +/- 5%; and left ventricular mass index, 113 +/- 28.9 versus
      121.9 +/- 39.4 g/m(2), respectively. Compared with pretransplant
      echocardiographic evaluations, similar reductions in left ventricular mass index
      were noted in both groups after transplantation. CONCLUSIONS: We observed that
      after renal transplantation there was a reduction of the LVH respect to the
      pretransplant dialytic status. The two immunosuppressive regimen did not
      influence the evolution of post-transplant LVH.

PMID- 24034018
TI  - Complications and graft survival in kidney transplants with vascular variants:
      our experience and literature review.
AB  - INTRODUCTION: In the literature several reconstructive techniques for vascular
      anastomoses in case of kidney graft vascular variants are reported. This article
      reports our experience in kidney transplants with vascular anomalies. MATERIALS
      AND METHODS: Between January 1996 and June 2012, 154 cadaveric kidney
      transplantations were performed at our center. In 35 case, vascular variants were
      found. Among the arterial variants we observed 27 double arteries, 2 cases with 3
      arteries, and 1 case with 4 arteries. All cases of Venous variants were double
      veins. Based on the type of reconstructive technique used, we divided transplants
      into group A (n = 22) separate multiple arterial anastomoses; group B (n = 8)
      anastomosis on the aortic patch; group C (n = 4) single anastomosis in case of 2
      arteries with a common ostium at the aortic origin. The venous variants were
      treated with ligation of the vein of smaller caliber. RESULTS: Kidney preparation
      to the back table lasted on average 50 minutes with no significant differences
      between the 3 groups and no significant timing increase compared to renal
      transplants without vascular anomalies (mean warm ischemia 40 minutes, range 30
      60 minutes). The mean cold ischemia time was limited to 16 hours from the removal
      and the mean warm ischemia was 50 minutes (range 30-70 minutes). There were no
      differences in timing between group C and single anastomoses, whereas groups A
      and B showed mean warm ischemia time was slightly increased compared to group C
      (P < .05). There were no significant differences in terms of delayed upturn of
      graft function and graft survival between groups A, B, and C and compared to
      transplants without vascular anomalies. CONCLUSIONS: In our series we observed
      similar results performing the reimplantation on aortic patch and separate
      multiple arterial anastomoses. Considering our experience, we believe that
      vascular variants are not an indication to exclude a graft for transplantation.

PMID- 24034019
TI  - Incidence of late deep venous thrombosis among renal transplant patients.
AB  - BACKGROUND: Kidney transplant recipients (KTRs) manifest hypercoagulable state
      that contributes to an increased incidence of deep vein thrombosis (DVT), not
      only early but also late in their course. KTRs display an imbalance of hemostatic
      mechanisms with a multifactorial rise in procoagulant factors, partly related to
      traditional risk factors and partly to transplantation. The aim of this study was
      to evaluate the incidence of first episodes of DVT among KTRs, focusing on risk
      factors. METHODS: From 2008 to 2011, we evaluated 30 kidney transplant patients
      who >=4 months there after transplantation developed DVT in the lower limbs only,
      lower limbs complicated by pulmonary embolism or retinal thrombosis. We analyzed
      causes of primary nephropathy, immunosuppressive regimen, post-transplantation
      infections, and erythrocytosis. DVT was diagnosed by color Doppler ultrasound or
      eye examination. RESULTS: A significantly increased incidence of DVT was observed
      among patients receiving cyclosporine or cyclosporine + mammalian target of
      rapamycin inhibitors, affected by polycystic kidney diseases, systemic lupus
      erythematosus or nephrotic syndrome, or displaying rapid and/or excessive
      correction of hematocrit values. DVT was not significantly related to an acute
      infection (cytomegalovirus) or to the prior dialysis modality. CONCLUSIONS:
      Hypercoagulability is a multifactorial condition in KTRs, representing a severe
      complication in stable patients. Prevention may consist of either accurate
      pretransplantation screening for thrombophilia or identification of patients at
      higher DVT risk.

PMID- 24034020
TI  - Laparoscopic approach for down-staging in hepatocellular carcinoma patients who
      are candidates for liver transplantation.
AB  - INTRODUCTION: The aim of this study was to assess the impact of laparoscopic
      thermoablation (LTA) and laparoscopic resection (LR) as neoadjuvant therapy
      before orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC).
      METHODS: From June 2005 to November 2010, 50 consecutive patients affected by HCC
      with liver cirrhosis were treated with LTA under ultrasound guidance or LR. Of
      them, 10 patients (mean age, 58.3 +/- 5.59 years; male:female, 8:2) underwent
      OLT. They were mostly Child-Pugh class A (80%). RESULTS: A LTA of 12 nodules was
      achieved in 7 patients and an LR of 3 HCC nodules in the other 3 subjects. The
      mean length of surgery was 163 minutes (range; 60-370). The mean hospital stay
      was 6.1 days. Transient mild postoperative liver failure was reported in 1 case.
      Complete tumor necrosis was observed in 10 thermoablated nodules (83.3%) via
      spiral computerized tomographic scan at 1 month after treatment; the resected
      patients showed absence of recurrence. All patients underwent OLT after a mean
      interval of 7 months. The histology of the native liver showed complete necrosis
      in 9/12 thermoablated nodules (75%); a recurrence at surgical site occurred in 1
      patient in the resection group. CONCLUSIONS: Laparoscopic ultrasound can be used
      in potential OLTs candidates to accurately stage HCC in advanced cirrhosis with
      minimal morbidity. LTA and LR proved to be safe and effective techniques for HCC
      patients, representing a valid "bridge" to OLT.

PMID- 24034021
TI  - From listing to transplant: nephrologic monitoring in cirrhotic patients awaiting
      liver transplantation.
AB  - Nephrologic monitoring of end-stage liver disease (ESLD) patients is part of
      evaluation for orthotopic liver transplantation (OLT). The numerous causes of
      renal dysfunction in ESLD patients sometimes relate to the extent of liver damage
      or sometimes more closely to organic nephropathy. The aim of this study was to
      evaluate renal function through a specific nephrologic form applied in our
      outpatient clinic to optimize nephrologic monitoring in ESLD patients awaiting
      OLT. We enrolled 69 cirrhotic patients (56 men, 13 women) awaiting OLT from April
      2008 to January 2012. All patients were evaluated at listing and every 3 months
      until OLT. The most interesting result was the stable values of serum creatinine
      from listing to transplantation. We think that dedicated liver transplant
      nephrologic evaluation is important in the follow-up of ESLD patients awaiting
      OLT, because the presence of renal dysfunction may represent an important
      criterion for specific therapeutic interventions to minimize pre-OLT renal
      injuries that limit the effect of impaired renal function on patient outcomes.

PMID- 24034022
TI  - Resistive index and MELD-Na: nephrologic monitoring in cirrhotic patients
      awaiting liver transplantation.
AB  - Renal dysfunction in cirrhotic patients is primarily related to disturbances in
      circulatory function. In decompensated cirrhosis, ascites and water retention are
      associated with development of dilutional hyponatremia. The arterial resistive
      index (RI) is a measure of resistance to arterial flow within the renal vascular
      bed. Hyponatremia is an independent predictor of mortality in patients with
      ascites. The aim of this study was to evaluate intrarenal RI in end-stage liver
      disease (ESLD) patients awaiting liver transplantation (LT) and its association
      with renal and hepatic function as assessed by Model for End-Stage Liver Disease
      (MELD) and MELD-Na scores. We evaluated 40 cirrhotic patients (23 males, 17
      females) awaiting LT from January 2009 to January 2012. Twenty-six of the 40
      patients (65%) showed a renal RI >= 0.70, the normal value according to standard
      reported evaluations. Patients with RI >= 0.70 showed significantly higher MELD
      and MELD-Na scores as well as greater higher serum creatinine and lower serum
      sodium concentrations compared with subject displaying RI <0.70. The most
      relevant result of our study was the strong association between elevated renal RI
      in ESLD patients and advanced liver dysfunction, as demonstrated by MELD and MELD
      Na scores, hyponatremia, ascites, and acute renal failure episodes. In
      conclusion, this study suggested that intrarenal RI assessment should be
      considered in the clinical and nephrologic monitoring of cirrhotic patients
      awaiting LT.

PMID- 24034023
TI  - Living-donor liver transplantation: donor selection criteria and postoperative
      outcomes. A single-center experience with a 10-year follow-up.
AB  - BACKGROUND: Donor safety must be considered to be a priority in live-donor liver
      transplantation (LDLT). The aim of this study was to evaluate these outcomes with
      special attention to surgical complications and their treatment. METHODS: From
      March 2001 to March 2012, 80 live donors underwent right hepatectomy (5-8
      segments). The middle hepatic vein was always left in the donor. Our
      retrospective study analyzed surgical outcomes and complications according to the
      Clavien classification modified for live donors. RESULTS: With a median follow up
      of 63.2 +/- 12.6 months, the mortality was 0%. Two donors experienced
      intraoperative complications, but all of them had complete recovery there after.
      Among the 22 complications in 17 donors (21.2%), 7 (8.7%) were major
      complications (Clavien grade 2b) but only 2 donors required surgical treatment.
      CONCLUSIONS: LDLT is a safe and feasible modality to alleviate the cadaveric
      donor shortage. The efficacy of this procedure is similar to that with deceased
      donors.

PMID- 24034024
TI  - Impact of Model for End-Stage Liver Disease score on transfusion rates in liver
      transplantation.
AB  - BACKGROUND: Liver transplantation (OLT) can entail a high risk of blood loss
      requiring transfusions, which increase morbidity and mortality. In recent years
      many efforts have been spent to improve the surgical and anesthetic management to
      decrease transfusion rates during OLT. Preoperative predictors for transfusion in
      OLT, remain uncertain. METHODS: We retrospectively reviewed the 219 OLT performed
      from 2005 to 2011 focusing on blood product (BP) transfusions. Statistical
      analysis sought the impact of transfusions on OLT outcomes to identify possible
      independent predictors of higher BP requirements. RESULTS: The 1- and 3-year
      survival rates were 86.6% and 76.45% for patients and 81.0% and 71.8% for grafts
      respectively. The mean intra- and perioperative red blood cell (RBC) transfusion
      rates were 12.3 +/- 11.7 U and 15.5 +/- 13.0 U respectively. A statistical
      analysis demonstrated a significant influence of BP transfusion on post-OLT
      complications and survivals. Multivariate logistic regression analysis showed the
      Model for End-Stage Liver Disease (MELD) score to be the only independent
      predictor of perioperative RBC transfusions. CONCLUSIONS: Our results confirmed
      the link between intra- and perioperative transfusions and outcome of OLT
      patients. MELD score resulted the only independent variable associated with
      increased perioperative RBC transfusions.

PMID- 24034025
TI  - Arterial anastomosis in liver transplantation for Rendu-Osler-Weber disease: two
      case reports.
AB  - Liver transplantation (LT) in patients with hereditary hemorrhagic telangiectasia
      (HHT), or Rendu-Osler-Weber, disease is a problematic procedure. In patients with
      hepatic involvement due to clinically significant arterovenous malformations,
      there is high risk of intraoperative bleeding and intra- or perioperative
      complications. Some surgical corrections have been proposed for venous problems,
      concerning the vena caval anastomosis. A common finding in HHT is arterial
      enlargement of the celiac trunk and of the common hepatic artery. We report 2
      cases of LT in HHT where the arterial anastomosis was successfully performed
      using the splenic artery of the recipient, which shows less tendency for
      enlargement than the celiac trunk.

PMID- 24034026
TI  - Multiple ways to manage portal thrombosis during liver transplantation: surgical
      techniques and outcomes.
AB  - BACKGROUND: Portal vein thrombosis (PVT) is a well-recognized complication of
      chronic liver disease with a prevalence ranging from 1% to 16%. MATERIALS AND
      METHODS: We performed a retrospective review of 447 consecutive patients who
      underwent liver transplantation (OLT) between October 2000 and December 2011
      comparing 51 recipients with PVT (study group) with 399 without PVT (control
      group). The aim of this study was to determine the impact of pre-existent PVT on
      the surgical procedure, to identify specific preventable perioperative
      complications, and based on our studies and other works, to determine whether
      this group of patients are acceptable candidates for OLT. RESULTS: Among the 51
      patients with PVT, 44 showed partial and 7 complete thrombosis. In 47 cases, we
      performed a thromboendovenectomy. There were six anastomoses at the confluence of
      the superior mesenteric vein (SMV) and one, with a venous graft interposition. In
      four complete thrombosis recipients we performed an extra-anatomic by pass
      between the main trunk of the SMV and the donor portal vein. Compared with the
      control group, regarding preoperative characteristics, PVT patients were older at
      the time of transplantation (P = .001) and had a higher use of TIPS (P = .02).
      The operative characteristics showed a longer warm ischemia time in the PVT group
      (46.9 +/- 22.5 vs 39.3 +/- 15 min; P = .004). There were significant differences
      in postoperative evaluations, nor in the complication rates. Overall survivals at
      10 years were similar: 61.7% versus 65.3%; (P = .9). CONCLUSION: Although PVT was
      associated with greater operative complexity, it had no influence on
      postoperative complications or overall survival.

PMID- 24034027
TI  - Recipient-donor age matching in liver transplantation: a single-center
      experience.
AB  - OBJECTIVE: The aim of this study was to investigate whether donor age was a
      predictor of outcomes in liver transplantation, representing an independent risk
      factor as well as its impact related to recipient age-matching. METHODS: We
      analyzed prospectively collected data from 221 adult liver transplantations
      performed from January 2006 to September 2009. RESULTS: Compared with recipients
      who received grafts from donors <60 years old, transplantation from older donors
      was associated with significantly higher rates of graft rejection (9.5% vs 3.5%;
      P = .05) and worse graft survival (P = .021). When comparing recipient and graft
      survivals according to age matching, we observed significantly worse values for
      age-mismatched (P values .029 and .037, respectively) versus age-matched
      patients. After adjusting for covariates in a multivariate model, age mismatch
      was an independent risk factor for patient death (hazard ratio [HR] 2.13, 95%
      confidence interval [CI] 1.1-4.17; P = .027) and graft loss (HR 3.86, 95% CI 1.02
      15.47; P = .046). CONCLUSIONS: The results of this study suggest to that
      optimized donor allocation takes into account both donor and recipient ages
      maximize survival of liver-transplanted patients.

PMID- 24034028
TI  - Use of grafts from anti-HBc-positive donors in liver transplantation: a 5-year,
      single-center experience.
AB  - INTRODUCTION: Liver transplantation (OLT) is the treatment of choice for advanced
      hepatic disease. The growing gap between waiting list patients and the number of
      donations has led to acceptance of less than optimal donors. The aim of this
      study was to evaluate the 5-year experience with anti hepatitis B core antigen
      (HBc)-positive liver donors. PATIENTS AND METHODS: All recipients of anti-HBc
      positive grafts from January 2005 to December 2010 were evaluated annually after
      OLT for liver disease etiology, Model for End-Stage Liver Disease (MELD) score,
      and the presence of hepatocellular carcinoma (HCC) liver biopsy histology and
      serology for hepatitis B virus (HBsAg, anti-HBs, HBV-DNA), hepatitis C virus, and
      hepatitis D virus as well as antiviral prophylaxis to prevent de novo HBV.
      RESULTS: Among the 249 OLT performed from January 2005 to December 2010, (9.3%)
      cases used grafts from anti-HBc-positive donors. Etiologics of liver disease
      among the recipients were HBV (n = 13; 32.5%), HCV (n = 13; 32.5%) or other
      causes (n = 14; 35%). In 20 of the 40 patients (50%), HCC was found in the
      explanted organ. Of 40 recipients of anti-HBc-positive grafts 11 died, and 7
      (17.5%) required retransplantation. Various regimens were employed as post
      transplantation antiviral prophylaxis: (l) Immune globulin (25.8%); (2) Oral
      antiviral drugs (9.7%); and (3) combined prophylaxis (51.6%) or no treatment
      (12.9%). No difference was observed in patient or graft survival in relation to
      the etiology of liver disease, the MELD score, or the presence of HCC at the time
      of OLT, except graft survival was significantly reduced among recipient who
      underwent transplantation for non-HBV or non-HCV liver diseases compared with
      those engrafted due to viral hepatitis (P = .0062). No difference was observed in
      histologic features (grading and staging) compared with the antiviral
      prophylactic therapy; the 2 patients (5%) who developed de novo HBV had not
      received prophylaxis after OLT. CONCLUSIONS: Matching anti-HBc-positive grafts to
      recipients without HBV infection before OLT, may be especially safe.

PMID- 24034029
TI  - Liver transplantation for hepatocellular carcinoma within Milan Criteria in
      patients with Model for End-Stage Liver Disease score below 15: the impact of the
      etiology of cirrhosis on long-term survival.
AB  - BACKGROUND: Liver transplantation (OLT) is the gold standard therapy for patients
      with cirrhosis complicated by hepatocellular carcinoma (HCC) within Milan
      Criteria (MC). We evaluated the impact of the etiology of the underlying liver
      disease on long-term outcomes of patients undergoing OLT for HCC within MC having
      a Model for End-stage Liver Disease (MELD) score < 15. METHODS: From November
      2002 to December 2009, we performed 203 primary OLTs from brain-dead donors in
      recipients with HCC and cirrhosis with biochemical MELD scores below 15. We
      excluded 31 patients outside MC on the explant pathology of the native liver. The
      remaining 172 were divided into 3 groups according to the etiology of the
      underlying cirrhosis: hepatitis C virus-positive (HCV+; n = 78; 45%), hepatitis B
      virus-positive (HBV+; n = 65; 38%) and other indications (n = 29; 17%). The
      groups were compared for donor and recipient features, donor-recipient match, and
      transplant variables. The study endpoint was long-term patient survival. RESULTS:
      The groups were similar, except for a greater prevalence of hepatitis B core
      antibody-positive grafts in the HBV+ group and less frequent HCC bridging
      procedures in the other indications group. After a median follow-up of 72 months,
      HCC recurrence was observed in 8 (4.7%) patients (6 HCV+, 2 other indications), 5
      of whom died. Overall 5-year patient survival of 82%, revealed significant
      differences among groups: 98.3% in HBV+, 67.1% in HCV+, and 85.8% in other
      indications (HBV+ vs other indications: P = .01; HBV+ vs HCV+: P = .0001; HCV+ vs
      other indications: P = NS). In the HCV+ group, recurrent HCV hepatitis was the
      most frequent cause of death. Upon multivariate analysis, HBV positivity in the
      recipient was an independent predictor of better patient survival (hazard ratio =
      0.10, 95% confidence interval 0.02-0.64, P = .013). CONCLUSIONS: Etiology of the
      underlying cirrhosis significantly influenced the long-term survival after OLT of
      patients with HCC within MC and MELD < 15. It should be taken into account in
      estimation of survival benefit.

PMID- 24034030
TI  - Hyperbilirubinemia after liver transplantation: the role of coupled plasma
      filtration adsorption.
AB  - Hyperbilirubinemia often accompanies liver failure; therefore, artificial liver
      support devices are currently used as a bridge to more definitive treatments to
      eliminate water-soluble and albumin-bound toxins. We report 2 patients, of which,
      after liver transplantation, the first experienced early allograft dysfunction
      and the other hyperbilirubinemia linked to chronic rejection. After 3 cycles of
      coupled plasma filtration adsorption (CPFA), the bilirubin promptly decreased in
      both cases. CPFA is an extracorporeal therapy that uses plasma filtration
      associated with an adsorbent cartridge and hemofiltration to remove cytokines and
      inflammatory mediators associated with septic shock, severe sepsis, and multiple
      organ dysfunction syndrome. Each cycle of treatment lowered the bilirubin of our
      patients by ~40%. CPFA deserves attention as a potential inexpensive short
      lasting device to treat hyperbilirubinemia after liver surgery or
      transplantation. Moreover, the effects of CPFA should be further studied to
      address inflammatory mediators in chronic rejection after liver transplantation
      or other immunologic disorders.

PMID- 24034031
TI  - Surveillance of bacterial and fungal infections in the postoperative period
      following liver transplantation: a series from 2005-2011.
AB  - Orthotopic liver transplantation (OLT) is a life-saving procedure for the
      treatment of many end-stage diseases, but infectious and acute rejection episodes
      remain major causes of morbidity and mortality. Bacterial and fungal infections
      can be due to intra-abdominal, biliary, respiratory, urinary, wound, central
      venous catheters (CVC) or unknown sources. Using the computerized database of our
      microbiology laboratory, we analyzed all the bacterial and fungal infections in
      the first three months following OLT among 151 consecutive adult recipients at
      single center between January 2005 and December 2011. Samples included blood,
      bile CVC, urine, and bronchoalveolar lavage (BAL) specimen. Culture and
      identification of the isolated microorganisms was done in accordance with
      standard microbiological procedures. Three hundred thirteen samples from the
      above sites showed positive results for gram-positive cocci (n = 137; 43.8%),
      gram-negative rods (n = 156; 49.8%), and Candida species (n = 19; 6.1%). One
      patient (0.3%) experienced a CVC-related infection caused by Fusarium oxysporum.
      Bacterial and particularly biliary tract infections seem to play major roles in
      morbidity and mortality in the first three months following OLT. The major
      contributors to patient morbidity and mortality were candidemia and/or invasive
      candidiasis mainly from the biliary tract and/or CVC-related infections.

PMID- 24034032
TI  - Incidence, management, and results of hepatic artery stenosis after liver
      transplantation in the era of donor to recipient match.
AB  - INTRODUCTION: Hepatic artery stenosis (HAS) is an important complication after
      liver transplantation. However, studies are not conclusive in terms of
      definition, incidence, best treatment, and timing of intervention. The aim of
      this study was to evaluate the incidence of SSHA that occurred in a single center
      over the past 12 years, pointing out diagnostic and therapeutic strategies.
      METHODS: The incidence of HAS was reviewed in 258 liver transplant recipients
      between January 1999 and December 2011. All patients underwent Doppler ultrasound
      (DUS) at fixed times. Multidetector computed tomographic angiography (MDCTA) was
      performed to confirm the DUS findings. RESULTS: HAS occurred in 23 cases (9.3%).
      In all cases diagnosis was performed by DUS resulting in a sensitivity of 100%
      and a specificity of 99.6%. Based on DUS and MDCTA data integration, in 10 cases
      we adopted the "wait and see" strategy, whereas 13 patients underwent
      interventional radiology techniques. CONCLUSION: DUS monitoring is efficacious in
      the diagnosis of HAS after liver transplantation. Interventional radiology
      procedures are safe and efficacious.

PMID- 24034033
TI  - Liver resection in transplanted patients: a single-center Western experience.
AB  - BACKGROUND: Liver resection (LR) in liver transplant (OLT) recipients, an
      extremely rare situation, who performed on 8 recipients. METHODS: This
      retrospective analysis of prospectively collected data concerned 8 (0.66%) 1198
      LR cases among OLT performed from 1997 to 2011. We analyzed demographic data,
      surgical indications, and postoperative courses. RESULTS: The indications were
      resectable recurrent hepatocellular carcinomas (HCC, n = 3), persistent fistula
      from a posterior sectorial duct (n = 1), recurrent cholangitis due to anastomotic
      stricture on the posterior sectorial duct (n = l), hydatid cyst (n = l), left
      arterial hepatic thrombosis with secondary ischemic cholangitis (n = 1), and a
      large symptomatic biliary cyst (n = 1). The mean interval time to liver resection
      was 23.7 months (range, 5-47). LR included right hepatectomy (n = 1), right
      posterior hepatectomy (n = 1), left lobectomy (n = 4), pericystectomy (n = 1), or
      biliary fenestration (n = 1). Which there was no postoperative mortality, the
      global morbidity rate was 62% (5/8). The mean follow-up after LR was 92 months
      (range, 11-156). No patients required retransplantation. None of the 3 patients
      who underwent LR for HCC showed a recurrence. CONCLUSIONS: LR in OLT recipients
      is safe, but associated with a high morbidity rate. This procedure can avoid
      retransplantation in highly selected patients, presenting a possible option
      particularly for transplanted patients with a resectable, recurrent HCC.

PMID- 24034034
TI  - De novo malignancies following liver transplantation: results from a multicentric
      study in central and southern Italy, 1990-2008.
AB  - OBJECTIVE: The objective of this study was to quantify incidence rates (IR) and
      risks of de novo tumors (except nonmelanoma skin cancers) in patients who
      underwent orthotopic liver transplantation (OLT) in central and southern Italy.
      METHODS: Data were collected on 1675 patients (75.5% males) who underwent OLT in
      six Italian transplantation centers in central and southern Italy (1990-2008).
      The time at risk of cancer (person years [PY]) was computed from OLT to the date
      of cancer diagnosis, death, or last follow-up, whichever occurred first. The
      number of observed cancer cases were compared with the expected one using data
      from population-based cancer registries. We computed gender- and age-standardized
      incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: During
      10,104.3 PYs (median follow-up, 5.2 years), 98 patients (5.9% of the total) were
      diagnosed with a de novo malignancy (for a total of 100 diagnoses). Twenty-two of
      these cancers were post-transplantation lymphoproliferative disorders (PTLD; 18
      non-Hodgkin lymphoma [NHL] and 2 Hodgkin's lymphoma [HL]), 6 were Kaposi's
      sarcoma (KS), and 72 were solid tumors (19 head and neck [H&N], 13 lung, 11 colon
      rectum, 6 bladder, and 4 melanoma). The overall incidence was 9.9 cases/10(3)
      PYs, with a 1.4-fold significantly increased SIR (95% CI, l.2-1.7). Significantly
      increased SIRs were observed for KS (37.3), PTLD (3.9), larynx (5.7), melanoma
      (3.1), tongue (7.1), and H&N (4.5) cancers. CONCLUSIONS: These results confirmed
      that OLT patients are at greater risk for cancer, mainly malignancies either
      virus-associated or related to pre-existent factors (eg, alcohols). These
      observations point to the need to improve cancer surveillance after OLT. The on
      going enrollment of patients in the present cohort study will help to elucidate
      the burden of cancer after OLT and better identify risk factors associated with
      its development.

PMID- 24034035
TI  - Incidence of upper aerodigestive tract cancer after liver transplantation for
      alcoholic cirrhosis: a 10-year experience in an Italian center.
AB  - INTRODUCTION: The aim of this study was to evaluate the incidence, clinical
      characteristics, treatment, and outcome of de novo tumors (DNT) of the upper
      aerodigestive tract in patients with alcoholic cirrhosis after orthotopic liver
      transplantation (OLT). METHODS: Among 225 consecutive OLT performed between
      January 2002 and January 2012, a total of 205 patients received a first liver
      allograft. Eleven (4.9%) patients developed DNT (lung, pancreas, bowel,
      esophagus, larynx, tongue, tonsil, and lymphoma). Among these, we observed 5
      patients with DNT of the upper aerodigestive tract. RESULTS: The 5 patients with
      DNT of the upper aerodigestive tract underwent OLT for alcoholic cirrhosis. There
      were 4 men and 1 woman with a mean age at transplantation of 47 years. The mean
      period of alcohol abuse was 90 months. The tumors occurred after a mean post
      transplantation time of 39 months. The immunosuppressive regimen included
      Tacrolimus, mTOR, mycophenolate mofetil (MMF), and low-dose steroids. We observed
      2 cases of squamous cell carcinoma of the esophagus, 1 case of tonsillar cancer,
      1 case of larynx carcinoma, and 1 case of tongue carcinoma. All patients
      underwent surgical excision. After surgery, 4 patients received chemotherapy and
      2 patients radiotherapy. At present, among the 5 patients with DNT of the upper
      aerodigestive tract, only 2 are alive without disease and 1 is alive with a local
      recurrence. CONCLUSION: The incidence of DNT of the upper aerodigestive tract
      after OLT is higher among patients receiving a transplant for alcoholic
      cirrhosis. This could be due to an additional effect of post-transplantation
      immunosuppression in patients exposed to alcohol before transplantation. We
      suggest a careful post-transplantation follow-up and more attention to improve
      early diagnosis.

PMID- 24034036
TI  - Tailored cytomegalovirus management in lung transplant recipient: a single-center
      experience.
AB  - INTRODUCTION: Among solid organ recipients lung transplant recipients are at
      highest risk to be affected by cytomegalovirus infection (CMV) or to die from CMV
      disease. Two strategies are usually adopted in the clinical management of
      transplant recipients: antiviral prophylaxis and pre-emptive therapy. METHODS: In
      our center we adopted from 2007 a combined prophylaxis with anti-CMV
      immunoglobulins in the first post-transplant year and antiviral therapy
      (gancyclovir or valgancyclovir) from post-transplant day 15 for 3 weeks and in
      case of CMV bronchoalveolar lavage specimen positivity (polymerase chain reaction
      or shell vial). Moreover, we studied specific cellular immune response by an
      Elispot assay to define responder patients by the number of spot forming units
      (<5 nonresponders, 5-20 weeks, 20-100 good, >100 very good responders). RESULTS:
      We reduced acute rejections (from 17% to 6%, odds ratio 3.25), lymphocytic
      bronchitis bronchiolitis (from 11% to 2%), and first-year CMV pneumonia after the
      first post-transplant month (from 6.4% to 1%). We showed in nonresponders an
      earlier onset (68 vs 204 post-transplant days) and a longer duration (>14 days vs
      <14 days) of infection (P < .05 for all referred data). DISCUSSION: The morbility
      reduction has been obtained by antiviral therapy, increasing costs and risk of
      side effects. Our more recent studies show a population with a good immune
      response that probably doesn't need a pharmacological intervention but just a
      strict follow-up. CONCLUSION: Our proposed strategy is now tailoring the therapy
      on immune response clinical application, limiting to the specimen positivity in
      nonresponders.

PMID- 24034037
TI  - Low-flow venovenous CO2 removal in association with lung protective ventilation
      strategy in patients who develop severe progressive respiratory acidosis after
      lung transplantation.
AB  - BACKGROUND: Primary graft dysfunction (PGD) might occur after lung
      transplantation. In some severe cases, conventional therapies like ventilatory
      support, administration of inhaled nitric oxide (iNO), and intravenous
      prostacyclins are not sufficient to provide an adequate gas exchange. The aim of
      our study was to evaluate the use of a lung protective ventilation strategy
      associated with a low-flow venovenous CO2 removal treatment to reduce ventilator
      associated injury in patients that develop severe PGD after lung transplantation.
      METHODS: From January 2009 to January 2011, 3 patients developed PGD within 24
      hours after lung transplantation. In addition to conventional medical treatment,
      including hemodynamic support, iNO and prostaglandin E1 (PGE1), we initiated a
      ventilatory protective strategy associated with low-flow venovenous CO2 removal
      treatment (LFVVECCO2R). Hemodynamic and respiratory parameters were assessed at
      baseline as well as after 3, 12, 24, and 48 hours. RESULTS: No adverse events
      were registered. Despite decreased baseline elevated pulmonary positive
      pressures, application of a protective ventilation strategy with LFVVECCO2R
      reduced PaCO2 and pulmonary infiltrates as well as increased pH values and
      PaO2/FiO2 ratios. Every patient showed simultaneous improvement of clinical and
      hemodynamic conditions. They were weaned from mechanical ventilation and
      extubated after 24 hours after the use of the low-flow venovenous CO2 removal
      device. CONCLUSION: The use of LFVVECCO2R together with a protective lung
      ventilation strategy during the perioperative period of lung transplantation may
      be a valid clinical strategy for patients with PGD and severe respiratory
      acidosis occured despite adequate mechanical ventilation.

PMID- 24034038
TI  - Inhaled nitric oxide versus sodium nitroprusside for preoperative evaluation of
      pulmonary hypertension in heart transplant candidates.
AB  - OBJECTIVE: The development of pulmonary hypertension before heart transplantation
      increases the risk for postoperative right ventricular failure. Reversibility of
      pulmonary vascular resistance (PVR), which indicates the feasibility of heart
      transplantation, can be tested with the use of intravenous vasodilators, such as
      sodium nitroprusside (NaNTP) or prostacyclin. However, the drawback of these
      drugs is the development of systemic hypotension. The aim of this study was to
      evaluate the safely and feasibility of inhaled nitric oxide (iNO) compared with
      sodium nitroprusside to test PVR reversibility, while avoiding systemic
      hypotension. MATERIALS AND METHODS: We included all patients who were affected by
      end stage heart failure undergoing evaluation for heart transplantation if they
      showed elevated PVR > 2.5 Wood units and mean pulmonary arterial pressure (mPAP)
      >25 mm Hg. The hemodynamic parameters measured by right heart catheterization
      were: systolic blood pressure (SBP), mPAP, pulmonary capillary wedge pressure,
      and cardiac index (CI). The following variables were derived: transpulmonary
      gradient (TPG) and PVR. All patients were tested by both iNO (20-40 ppm) and
      intravenous NaNTP, at increasing dosages which were titrated based on systemic
      pressure. We randomly assigned the order of administration of iNO and NaNTP.
      RESULTS: The 9 male candidates has an average age of 56 +/- 4 years. Seven of the
      9 (71%) had postischemic cardiomyopathy, and 2 had idiopathic cardiomyopathy. We
      observed a reduction of mPAP (32% and 14%), PVR (41% and 32%), TPG (20% and 26%),
      and SBP (17% and 5%) and an increase of CI with administration of NaNTP and iNO,
      respectively. CONCLUSIONS: We observed a reduction in PVR and mPAP with
      administration of either iNO and NaNTP. A better effect of NaNTP was attributed
      to reducted post-load of the left ventricle. However, the main advantage of iNO
      was the absence of systemic hypotension and its selectivity for pulmonary
      vascular system, as underscored by TPG reduction.

PMID- 24034039
TI  - Pathfast presepsin assay for early diagnosis of bacterial infections in surgical
      patients: preliminary study.
AB  - BACKGROUND: Various biomarkers have been studied for diagnosing bacterial
      infections, seeking to stop the sepsis cascade. Presepsin, which is ~13 kDa in
      size, has been identified to increase specifically in the blood of sepsis
      patients. Additionally, measurement of presepsin is useful to evaluate the
      severity of infection and monitor clinical responses. We evaluated the analytical
      and clinical performance of the Pathfast presepsin (PFP) assay system for early
      diagnosis of infection. MATERIALS AND METHODS: From November 2011 to June 2012 we
      studied 70 adult patients, including 35 cadaveric organ transplant recipients and
      35 abdominal surgery patients. The 32 female and 38 male subjects had a mean age
      of 56.1 years (range, 19-70). Heparinized whole blood for PFP assay was tested at
      48 hours after surgery together with blood cultures. RESULTS: The mean presepsin
      level (PL) in the 50 positive patients was 3,957.45 pg/mL (range 255-20,000). For
      transplant patients, PL was 3,034.43 +/- 2,880.791 pg/mL, with 30 positive
      results. Microbiologic findings confirmed the presence of bacterial infections
      within 69 +/- 2.5 hours from enrollment despite that when the test was performed,
      70% showed no sign or symptom of infection. In 15 abdominal surgery patients, the
      PFP test was negative with negative blood cultures. The positive PFP test in 20
      other abdominal surgery patients showed PL of 2,363 +/- 7,988.47 pg/mL in the
      absence of signs or symptoms of infection in 25% of them. The 20 positive
      patients showed positive blood cultures within 67 +/- 1.8 hours from enrollment.
      CONCLUSIONS: The PFP test had a (100%) sensitivity to show the presence of
      infection in a short time (15 min), confirmed by positive blood cultures.

PMID- 24034040
TI  - Evaluation of Epstein-Barr virus-specific immunologic response in solid organ
      transplant recipients with an enzyme-linked ImmunoSpot assay.
AB  - Epstein-Barr virus (EBV) is a gamma-herpes virus, responsible for infectious
      mononucleosis in immunocompetent hosts. Cellular immunity appears rapidly during
      EBV primary infection, keeping it silent despite long-life persistence in B
      lymphocytes. Defects of the EBV-specific cellular immunity are supposed to be the
      basis of post-transplantation lymphoproliferative disorders, promoted by high
      levels of immunosuppression. We retrospectively reviewed 197 solid organ
      transplant recipients to investigate EBV-specific lymphocyte responsiveness using
      Enzyme-linked ImmunoSpot assay (EliSpot), which assesses the EBV-specific
      interferon (IFN)-gamma producing peripheral blood mononuclear cells, and kinetics
      of EBV infection/reactivation post-transplantation using quantitative real-time
      polymerase chain reaction (PCR) on whole blood. Overall, 102 of the 197 patients
      (51.8%) showed EBV responsiveness at the EBV-EliSpot assay: 68 (66.6%) showed a
      persistently positive EBV response in 3 or more determinations and 34 (33.3%) had
      transient episodes of nonresponsiveness. Ninety-five (48.2%) patients were
      persistently EBV nonresponders. EBV-DNAemia data were available for 58 patients:
      27.6% presented at least one episode of EBV-DNA occurrence. No differences were
      found in EBV-EliSpot response stratification between the groups of patients who
      experienced episodes of EBV reactivation and those without EBV-DNAemia. However,
      EBV DNAemia peak values tended to be higher in the first year post
      transplantation in the group of patients with a persistent positive EBV-specific
      immune response. EBV viral load quantitation in blood and EliSpot EBV-specific
      immune response determination may represent a powerful tool for monitoring solid
      organ transplant recipients, guiding immunosuppression modulation in patients
      with active EBV replication.

PMID- 24034041
TI  - Quality of life and energy expenditure in transplant recipient football players.
AB  - Football (soccer) is a highly motivating leisure activity with important
      potential as a health-promoting activity also for transplant recipients. The aim
      of this study was to assess the "on the field" energy expenditure during football
      games and the quality of life of transplant recipients practicing football.
      Twenty-two recipients of kidney (n = 11), bone marrow (n = 7), liver (n = 3) or
      corneal (n = 1) transplantations had an overall mean age of 37 +/- 9 years, body
      mass index of 23.5 +/- 2.4 kg/m(2), and time after transplantation of 9.3 +/- 6.4
      years. They were compared with 25 healthy football players of mean age 41 +/- 10
      years and body mass index of 26.3 +/- 3.9 kg/m(2). There were no significant
      differences between transplant recipients and controls regarding mean energy
      expenditure (393 +/- 113 vs 392 +/- 132 kcal/h) number of steps (3.978 +/- 1.317
      vs 3.933 +/- 1.563) during, and capillary blood lactate concentrations (4.8 +/-
      0.9 vs 5.2 +/- 1.3 mmol/L) after the matches. The SF-36 questionnaire
      administered before the matches showed transplant recipient players to score
      significantly worse in the scales of general (P < .05) and mental health (P <
      .01). This study indicated that transplant recipients involved in football
      matches attained a level of energy expenditure and a quality of life consistent
      with a healthy lifestyle. Football has the potential to be implemented as a
      permanent health-promoting activity also for transplant recipients.

PMID- 24034042
TI  - For anti-HLA-specific donor antibodies detection by flow cytometry cytotoxic
      crossmatches comparison of methods.
AB  - Anti-HLA-specific donor antibodies induce rapid, irreversible destruction of the
      transplant (hyperacute rejection) that today happens rarely due to immunologic
      studies-prospective crossmatch-of patients awaiting the kidney graft. The usual
      approach for pretransplant donor/recipient evaluation is based on 2 methods: (1)
      the cytotoxic complement crossmatch (CDC) and (2) the flow cytometric crossmatch
      (FCX). The CDC crossmatch is positive when complement-fixing antibodies are
      present, an absolute contraindication to kidney transplantation. The more
      sensitive FCX-positive crossmatch detects low concentrations of unable to fix
      performed antibodies complement. It is an "index" of possible damage due to
      accelerated rejection. The target of our study was to develop a cytotoxic flow
      cytometry crossmatch (cFCX) that detected cytotoxic antibodies move sensitively
      than the traditional CDC method and also was less subjective and more
      standardized for interpretation studying sera from 23 patients; the cFCX showed
      the requested efficiency characteristics even in an emergency. In addition, the
      new method permited one to calculate a cutoff for positivity (average value of
      the negative control + 2 standard deviations), assuring an "objective"
      interpretation of the results that agreed with the CDC but was more sensitive and
      accurate allowing solution of ambiguous results for cases of "doubt"-positive CDC
      crossmatch. Furthermore, our aim was to correlate the effect of the strength of
      the anti-HLA antibodies determined by mean fluorescence intensity value of
      LabScreen Single Antigen beads with results of CDC, cFCX, and FCX methods.

PMID- 24034043
TI  - Combined kidney and vascularized total bladder transplantation: experience in an
      animal model.
AB  - BACKGROUND: Few reports have described a partial bladder graft with an en bloc
      kidney transplantation, mainly to facilitate reconstruction of the urinary tract,
      but also to augment the native bladder. The present study assessed the
      feasibility to graft vascularized total bladder in association with a renal
      transplantation. METHODS: The right kidney, in continuity with the ureter and the
      entire bladder, was retrieved from three female pigs weighing 20 g. The visceral
      bloc was transplanted to three recipient pigs of the same weight. The entire
      bladder was transplanted with its vascular connection to ensure a better blood
      supply. After 3 days of observation, one recipient was humanely killed to examine
      the bladder graft. Oxygen saturation in the bladder graft monitored for 8 hours
      was compared with the native bladder in the other two recipients. All three
      bladder grafts were examined by a pathologist. RESULTS: All bladder grafts seemed
      to be macroscopically well-perfused upon removal of the vascular clamps. In case
      1, the recipient was clinically well with good urinary output over the first 2
      days of observation; is contrast, on day 3 the animal displayed an acute reduced
      urinary output. Laparotomy on day 3 of observation showed recent thrombosis of
      the bladder and renal graft vessels. In cases 2 and 3, oxygen saturations of the
      bladder graft were normal during the 8-hour observation period, without any
      difference between the graft and the native bladder. CONCLUSIONS: According to
      our results, vascularized total bladder transplantation is feasible. In
      combination with renal transplantation, it could be applied as an alternative to
      bladder augmentation or total bladder replacement.

PMID- 24034044
TI  - Liver transplantation in children with congenital cardiac defects: a case report
      and a short literature review.
AB  - Advances in surgical techniques and follow-up of patients with complex congenital
      heart disease who were corrected in childhood increasingly survive to adolescence
      or adulthood. Increasingly anesthesiologists encounter these cases for major
      noncardiac surgery, including orthotopic liver transplantation (OLT) wherein
      there is an augmented risk of significant perioperative hemodynamic instability.
      We performed a successful OLT in a 12-year-old boy with end-stage cryptogenetic
      liver fibrosis and hepatopulmonary syndrome who was born with a double outflow
      right ventricle, pulmonary atresia, and pulmonary artery hypoplasia corrected at
      the age of 1 month. By the time he was considered for OLT his altered pulmonary
      valve apparatus resulted in severe pulmonary regurgitation, dilated right atrium
      and ventricle, and elevated right heart pressures. After a temporarily successful
      angioplasty he was at first placed on the waiting list, then removed, and finally
      relisted following implantation of a prosthetic pulmonary valve that resulted in
      significant reduction of right heart pressures.

PMID- 24034045
TI  - Extracorporeal membrane oxygenation rescue therapy in a case of portopulmonary
      hypertension during liver transplantation: a case report.
AB  - Portopulmonary hypertension has been reported in 2% to 9% of candidates for liver
      transplantation (OLT). If it is moderate to severe, it represents a
      contraindication to the procedure until pulmonary vasodilatative therapy has been
      optimized. We report the case of a 43-year-old man, scheduled for OLT due to
      alcoholic cirrhosis with hemosiderosis. His Model for End-Stage Liver Disease was
      25 at that time. The preoperative evaluation showed a severe alteration of
      diffusion (pO2 68 mm Hg), without hepatopulmonary syndrome or portopulmonary
      hypertension (PPH) upon basal and dobutamine stress echocardiography. At the
      beginning of the OLT the hemodynamic profile showed mean pulmonary artery
      pressure (mPAP) 38 mm Hg, wedge pressure (WP) 19 mm Hg, cardiac output (CO) 9.1
      L/min, pulmonary vascular resistance (PVR) 166 dyne s/cm(5), transpulmonary
      gradient (TPG) 19 mm Hg, which lead us to promptly initiate inhaled nitric oxide
      (iNO) and intravenous epoprostenol 2 to 5 ng/kg/min. Upon graft reperfusion the
      hemodynamic profile was: mPAP 47 mm Hg, WP 23 mm Hg, CO 14.2 L/min, PVR 135 dyne
      s/cm(5), TPG 24 mm Hg, and at the end of surgery, mPAP 39 mm Hg, WP 20 mm Hg, CO
      10.6 L/min, PVR 123 dyne s/cm(5), TPG 19 mm Hg. On postoperative day (POD) 3, we
      observed severe worsening of PPH: mPAP 60 mm Hg, WP 10 mm Hg, CO 9.8 L/min, PVR
      395 dyne s/cm(5), TPG 50 mm Hg even with maximal pulmonary vasodilatatory therapy
      (ambrisentan 5 mg, intravenous sildenafil 20 mg * 3 and epoprostenol 22
      ng/kg/min, iNO). Severe acute respiratory distress syndrome (ARDS) was presents.
      Therefore we decided to begin veno-venous extracorporeal membrane oxygenation (v
      v ECMO) to correct the hypoxic vasoconstriction. Subsequent weaning from
      inotropic support with iNO and epoprostenol was possible on POD 7 due to mPAP 42
      mm Hg, WP 15 mm Hg, CO 7.9 L/min, PVR 273 dyne s/cm(5), and TPG 27 mm Hg. On POD
      11 he was weaned from ECMO due to: mPAP 40 mm Hg, WP 16 mm Hg, CO 6.5 L/min, PVR
      295 dyne s/cm(5) and TPG 24 mm Hg. The patient was extubated on POD 17. The
      cardiac catheterization 1 month after OLT showed: mPAP 28 mm Hg, WP 13 mm Hg, CO
      5.4 L/min, PVR 220 dyne s/cm(5) and TPG 15 mm Hg. ECMO rescue therapy in this
      "extreme" case allowed us to correct hypoxemia responsible for worsening of
      pulmonary hypertension allowing time to reach the goal of vasodilatatory therapy.

PMID- 24034046
TI  - Two brothers with renal and hepatic polycystic disease treated with combined
      liver and kidney transplantation: a case report.
AB  - We report two brothers with renal and hepatic polycystic disease who developed
      end-stage renal failure, requiring hemodialysis, and organomegaly syndrome
      related to the gigantic size of the liver and both kidneys. Although there was no
      liver failure, combined liver and kidney transplantation was performed owing to
      worsening of the clinical condition. In both cases, successful transplantation
      was accomplished with intra-abdominal engraftment of the liver and kidneys
      through the same abdominal incision. 

PMID- 24034047
TI  - A case report of AA amyloidosis associated with familial periodic fever syndrome
      diagnosed after kidney transplantation: never say never.
AB  - Recurrent or "de novo" AA amyloidosis in the renal allograft is rarely described.
      We describe a case of severe nephrotic syndrome in a recipient of a kidney graft
      with a previous diagnosis of polycystic nephropathy caused by AA amyloidosis
      diagnosed only after the renal transplantation. The disease was possibly a tumor
      necrosis factor receptor-associated periodic syndrome (TRAPS). TRAPS is a rare
      hereditary inflammatory disease never reported to the best of our knowledge, as a
      de novo diagnosis in the transplantation setting. Biopsy of the renal graft,
      indicated for the onset of heavy proteinuria, and genetic investigation provided
      the clues for diagnosis. 

PMID- 24034048
TI  - Deep vein thrombosis as debut of cytomegalovirus infection associated with type
      II cryoglobulinemia, with antierythrocyte specificity in a kidney transplant
      recipient: a case report.
AB  - Immunologic alterations, such as cryoglobulinemia, have been described in the
      acute phase of primary cytomegalovirus (CMV) infections in immunocompetent
      patients. There are few references about these influences of a primary CMV
      infection in an at-risk kidney transplant recipient (donor positive/recipient
      negative-D(+)/R(-)). Herein we have described the case of a 46-year-old man, who
      was naive for CMV and underwent renal transplantation from a CMV+ cadaveric
      donor, thereby at high risk for disease transmission. The immunosuppression
      consisted of basiliximab, tacrolimus, mycophenolate mofetil, and steroids. The
      recipient was not treated with CMV prophylaxis, but rather regularly screened for
      possible pre-emptive treatment. At 35 days after transplantation, he was admitted
      because of deep vein thrombosis (DVT) in the transplant ipsilateral lower limb
      accompanied by oliguria, fever, and epigastric pain accompanied by type II
      cryoglobulinemia and acute CMV infection. The direct antiglobulin test (DAT) for
      C3d was positive. The cryoglobulins displayed anti-red blood cell specificity,
      with maximum activity at 4 degrees C. The DVT was successfully treated with
      locoregional thrombolysis in combination with anticoagulant therapy. The DAT
      improved with CMV treatment and increased steroid therapy. The urine output and
      renal function tests improved with resolution of the thrombosis, achieving
      complete recovery without sequelae. Our hypothesis was that CMV infection
      triggered cryoglobulinemia. The blood disorder caused hyperviscosity, inducing
      DVT. This case, of CMV infection showed associated cryoglobulinemia presenting
      with antierythrocyte specificity in a kidney transplant recipient.

PMID- 24034049
TI  - A newly identified mutation in the complement factor I gene not associated with
      early post-transplant recurrence of atypical hemolytic-uremic syndrome: a case
      report.
AB  - Atypical hemolytic uremic syndrome (aHUS), which can recur after renal
      transplantation, is associated with poor graft outcomes. The underlying genetic
      defect, namely, mutations in genes coding for the complement factor H, I (CFI),
      or membrane cofactor protein, greatly impacts the risk of aHUS recurrence. We
      report here the case of a patient with chronic renal failure due to aHUS in which
      screening for complement mutations, performed before wait-listing for kidney
      transplantation, showed a never described previously heterozygous mutation in the
      exon II of the CFI gene. Specifically, this mutation leads to a substitution of
      cytosine for guanosine at nucleotide 148, resulting in the change at amino acid
      50 from arginine to proline. Subsequently, he received a renal allograft from
      deceased donor. Good graft function was established immediately, without clinical
      features of aHUS. Due to a lack of data on this mutation, we avoided prophylactic
      treatment for aHUS but closely monitored biochemical markers of aHUS to treat a
      possible recurrence. Immunosuppressive treatment was based on basiliximab,
      tacrolimus, steroids, and mycophenolic acid. At the time of discharge the serum
      creatinine was 1.4 mg/dL. Ten months after transplantation the patient is doing
      well without evidence of aHUS. Our case suggested that a heterozygous mutation in
      exon II of the CFI gene was not associated with a risk of early post-transplant
      aHUs recurrence adding new knowledge on complement mutations implicated in aHUS
      post-transplant recurrences.

PMID- 24034050
TI  - Complete clinical remission of psoriasis 6 months after renal transplantation.
AB  - BACKGROUND: Psoriasis, one of the most common immune-mediated inflammatory
      diseases of the skin is mediated by activated effector T cells. CASE REPORT: We
      report a case of a 56-year-old white man with a 22-year history of severe
      psoriasis vulgaris with plaque and joint involvement, who experienced a complete
      clinical remission after renal transplantation. The patient had been on
      hemodialysis for 6 years because of chronic renal failure caused by an
      undetermined chronic nephropathy. Psoriasis, which worsened over the years, was
      symmetrically distributed as erythematous scaly plaques that had increased until
      they covered about 50% of the body surface, involving mainly the abdomen, legs,
      back, and arms. The patient also complained of severe itching an responsive to
      drugs. He had been treated with topical and systemic corticosteroids and
      phototherapy several times without benefit. After renal transplantation he
      underwent immunosuppressive therapy with corticosteroids, mycophenolate mofetil
      (MMF), and tacrolimus (Advagraf, beginning starting dose 1 mg/kg/day, C0 10
      ng/mL). RESULTS: From the early days post-surgery the patient reported a fast
      improvement in the itching with progressive reduction of the skin lesions. After
      4 months follow-up the psoriasis had completely regressed, presumably due to the
      immunosuppressive regimen. CONCLUSION: This finding suggests that systemic
      immunosuppressive drugs may be useful for psoriasis an responsive to conventional
      therapy.

PMID- 24034051
TI  - Plasmacytoma-like post-transplantation lymphoproliferative disorder confined to
      the renal allograft: a case report.
AB  - A 44-year-old woman who had end-stage kidney disease from diabetes and
      hypertension underwent a deceased donor kidney transplantation. Eighteen months
      after the transplantation she developed an abrupt increase in her creatinine
      level and a kidney biopsy specimen showed the presence of a plasma cell-rich
      infiltrate. A vast majority of the plasma cells were kappa (kappa) light chain
      restricted on in situ hybridization. kappa and lambda (lambda) free light chain
      were elevated in her serum and so was the kappa/lambda ratio. A bone marrow
      biopsy specimen showed no evidence of clonal plasmacytosis. A positron emission
      tomography (PET) scan showed hypermetabolic activity confined to the kidney.
      Prior to transplantation she was Epstein-Barr virus (EBV) immunoglobulin (Ig)G
      negative but had detectable EBV based on polymerase chain reaction (PCR) in her
      blood during this episode. Despite reduction in immunosuppression there was no
      change in the kappa/lambda ratio and her renal function worsened. She underwent a
      transplant nephrectomy and her kappa/lambda ratio became normal. Twenty-one
      months later she is lymphoma-free and doing well on dialysis. Plasmacytoma-like
      post-transplantation lymphoproliferative disorder (PTLD) is rare and even more is
      the localization of the malignancy to the allograft. When reduction of
      immunosuppression is unsuccessful in treatment, removal of the organ may be
      necessary as is demonstrated in our case.

PMID- 24034052
TI  - Headaches after renal transplantation--a case report.
AB  - Headaches are one of the most common medical complaints. The differentiation of
      benign primary headaches from the small number of patients with secondary
      headaches may be challenging, but failure to recognize a serious headache can be
      fatal. We report the case of a 49-year-old renal transplant patient, who was
      admitted to hospital because of intractable right-sided headaches. Cerebral
      imaging was unremarkable. Not until 2 days later did the patient develop a rash
      of grouped vesicles located in the right dermatome C3. Consecutively
      cerebrospinal fluid tested positive for Varizella zoster virus (VZV), indicating
      VZV meningitis. Therapy was started with intravenous acyclovir with rapid
      improvement. Here in we have described an atypical case of VZV reactivation in a
      renal transplant patient, who initially presented with headaches without any skin
      manifestation. Because of their compromised immune system, transplant patients
      have a high risk for visceral involvement of VZV infections, which are a life
      threatening emergency. Therefore, vaccination of seronegative patients should be
      part of the pretransplant workup. Accurate and fast diagnosis of infection is
      essential to immediately start antiviral therapy.

PMID- 24034053
TI  - Tuberculous sacroiliitis in a renal transplant recipient: a case report.
AB  - Although Mycobacterium tuberculosis (TB) is the predominant infectious disease
      after solid organ transplantation worldwide, extrapulmonary involvement in the
      sacroiliac (SI) joint has never been reported in renal transplant patients.
      Herein we have described a 59-year-old man who presented with left hip pain and
      fever at 1 year after renal transplantation. He had a positive Patrick's test on
      the left hip, elevated serum C-reactive protein, and widening of left SI joint on
      pelvic radiograph. Although the initial workup including blood culture, acid-fast
      stain, and tumor markers was nonrevealing, whole body bone scan and magnetic
      resonance imaging were suggestive of left sacroiliitis. Surgical debridement with
      biopsy confirmed mycobacterium TB infection. After a complete course of anti-TB
      treatment, his symptoms significantly resolved. Given the inconspicuous and
      protean symptoms of extrapulmonary TB, a high index of suspicion for TB
      sacroiliitis in renal transplant recipients with unexplained hip pain is
      warranted for early diagnosis and prompt treatment.

PMID- 24034054
TI  - Successful renal transplantation from a brain-dead deceased donor who died from
      snakebite: a case report.
AB  - Even though India is the country with the highest annual number of deaths
      (50,000) from snakebite, there is contradictory evidence regarding acceptance of
      deceased donors (DD) who died from this cause. We present 2 successful renal
      transplantations (RTx) from a brain-dead DD who died from a neurotoxic snakebite
      without manifestations of a viper bite. We accepted the donor as he exhibited no
      evidence of hematoxic snakebite. Rather the findings were consistent with a
      neurotoxic bite (probably krait), which can cause hypoxic brain injury. Both
      recipients established good diuresis intraoperatively and did not require
      hemodialysis. The patients were discharged with good diuresis and normal serum
      creatinines. After 3-month follow-up, both recipients show normal graft function.
      According to our experience of favorable RTx outcomes from a brain-dead DD who
      died from neurotoxic snakebite may expand the donor pool.

PMID- 24034055
TI  - Chest pain after kidney transplantation owing to pneumomediastinum: a case
      report.
AB  - BACKGROUND: Chest pain in kidney transplant recipients can signify a life
      threatening condition. CASE REPORT: A patient with polycystic kidney disease who
      underwent living donor kidney transplantation with open bilateral native
      nephrectomy developed acute substernal chest pain 10 days post-transplantation.
      History, physical, and diagnostic studies identified no cardiac or pulmonary
      causes for the pain, but radiography showed mediastinal air. No vascular or
      thoracic injury explained the development of the pneumomediastinum. After 1 day
      on oxygen, the chest pain symptoms resolved. Repeat x-rays showed resolution of
      the pneumomediastinum. DISCUSSION: Pneumomediastinum resulting from air migrating
      from the abdominal cavity to the thorax has not been described after open removal
      of diseased abdominal organs. This case illustrates that creation of a potential
      space in the abdominal cavity can be associated with the development of
      pneumomediastinum. CONCLUSIONS: Conservative measures were sufficient to resolve
      the pneumomediastinum and symptoms in this patient.

PMID- 24034056
TI  - Acute renal failure caused by hyperuremic acidemia in ABO-incompatible kidney
      transplant maintained with cyclosporine and high-dose mizoribine: a case report.
AB  - INTRODUCTION: The shortage of cadaver organs has led to expansion of living donor
      kidney transplantations with, 30% increase among ABO-incompatible cases in Japan
      and the use of marginal extended donors. Herein we have reported the outcome
      after an ABO-incompatible kidney transplantation from an aged living-related
      donor who suffered from mild diabetes mellitus and hypertension. CASE REPORT: A
      48-year-old man underwent ABO-incompatible kidney transplantation from his 76
      year-old father, using anti-CD20 antibody induction, followed by cyclosporine
      (CsA), mycophenolate mofetil (MMF), and prednisolone. After the operation, MMF
      was switched to high-dose mizoribine (MZ). He was discharged from the hospital on
      postoperative day (POD) 28 with a serum creatinine (sCr) of 1.47 mg/dL. On POD 34
      when the sCr was 8.14 mg/dL, his urine examination showed uric acid crystals with
      serum uric acid of 24.6 mg/dL. Biopsy findings showed no evidence of acute
      rejection but mild tubulointerstitial injury. Hemodialysis performed twice to
      reduce uric acid was accompanied by hydration. CsA/MZ was switched to
      tacrolims/MMF; benzbromarone, to febuxostat to treat hyperuric acidemia. On POD
      58, sCr reduced to 1.75 mg/dL he was discharged. On POD 416, graft function was
      stable with sCr of 1.70 mg/dL. CONCLUSION: Common side effect of MZ is
      hyperuricemia which presumably caused acute renal failure of this aged marginal
      donor kidney.

PMID- 24034057
TI  - An odd application of artificial vascular graft in the kidney transplantation of
      a patient with severe deep vein thrombosis: a case report.
AB  - Transplantation of a living-related donor kidney was performed for a 41-year-old
      man. The planned right donor nephrectomy from the patient's 64-year-old father
      was uneventful. However the recipient's bilateral iliac veins and inferior vena
      cava were occluded, requiring a connection of the donor renal vein to the
      recipient's right great saphenous vein using an artificial vascular graft. On
      postoperative day 9, the patient recovered normal renal function with a serum
      creatinine that gradually decreased to 1.399 mg/dL. Color Doppler and computed
      tomography angiography imaging showed patency of the artificial vascular graft
      with no evidence of thrombosis. In addition, warfarin was used to improve his
      protein S deficiency. 

PMID- 24034058
TI  - Breast involvement with post-transplant lymphoproliferative disease in a renal
      transplant recipient.
AB  - Post-transplant lymphoproliferative disease (PTLD) is a life-threatening
      complication among 1% to 20% of all organ transplant recipients. The majority of
      cases, if not all, are associated with Epstein-Barr virus (EBV) infection. Herein
      we report a 28 year-old woman who developed EBV-related PTLD in both her breasts
      at 12 years after renal transplantation. The purpose of this case description was
      to document the imaging findings in the breast associated with PTLD. 

PMID- 24034059
TI  - Aggressive pulmonary calcification developed after living donor kidney
      transplantation in a patient with primary hyperparathyroidism.
AB  - Metastatic pulmonary calcification, defined as calcium deposition in the intact
      lung, is commonly seen in patients with chronic renal failure, and it is known to
      be a benign clinical condition when detected by chance in an asymptomatic
      patient. Here we report the case of a 33-year-old woman who developed rapid and
      aggressive metastatic pulmonary calcification shortly after a living donor kidney
      transplantation, which induced acute antibody-mediated rejection. The patient's
      metastatic pulmonary calcification was successfully improved by extensive
      treatment for graft rejection, the correction of her accompanying primary
      hyperparathyroidism, and medical treatment with a bisphosphonate and sodium
      thiosulfate. Aggressive pulmonary calcification is reported as a rare
      complication seen in patients who have undergone a failed renal transplantation.
      A failed renal graft and accompanying secondary hyperparathyroidism seem to
      accelerate metastatic calcification. Most of the patients who develop aggressive
      pulmonary calcification suffer from the rapid progression of dyspnea and
      occasionally fever, and they die of respiratory failure. Pulmonary calcification
      should be considered in a patient developing dyspnea and unexplained pulmonary
      infiltrate, especially in the context of renal graft rejection; otherwise the
      prognosis of the patient will be very poor. 

PMID- 24034060
TI  - Refractory and massive lymphocele in a transplant patient with encapsulating
      peritoneal sclerosis treated with a single infusion of bleomycin: a case report.
AB  - A 26-year-old Caucasian man developed a large lymphocele after living-related
      kidney transplantation necessitating repeated drainage of large volumes every
      other day owing to ureteral compression. An open laparotomy for internal drainage
      was unsuccessful because of severe encapsulating peritoneal sclerosis. Prolonged
      external drainage with a catheter was inefficient. Repeated fine-needle
      aspirations of large volumes were needed to maintain ureteral patency over a
      period of 4 months. Finally, a single instillation of bleomycin immediately and
      effectively treated the lympocele with no relapse over the following 5 years. The
      presence of encapsulating peritoneal sclerosis seemed to be an obstacle to
      surgical treatment.

PMID- 24034061
TI  - Urgent liver transplantation for chemotherapy-induced HBV reactivation: a
      suitable option in patients recently treated for malignant lymphoma.
AB  - BACKGROUND: Hepatitis B (HBV) reactivation induced by chemotherapy is a problem
      currently encountered in the management of malignancies. HBV reactivation occurs
      particularly in patients who were not checked for HBV status, and therefore have
      not undergone antiviral prophylaxis. HBV reactivation may ultimately lead to
      fulminant liver failure (FLF). Liver transplantation (OLT), the only remaining
      effective treatment option, is generally denied for subjects with a recent
      history of malignancy. CASE REPORTS: We described retrospectively three cases of
      FLF caused by HBV reactivation in two men and one woman undergoing rituximab
      containing chemotherapy for malignant lymphomas: follicular, diffuse large B-cell
      and lymphoplasmacytic types. The two men reactivated after eight cycles of
      rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone and the
      one woman after 13 cycles of rituximab monotherapy; their hematologic disease was
      in remission. All three patients were hepatitis B surface antigen (HBsAg)
      positive with high HBV DNA levels. Neither man had been screened for HBV before
      chemotherapy; the woman had been treated with lamivudine (LAM) experiencing an
      HBV flare-up due to emergence of LAM resistance. All patients fulfilled King's
      College criteria for urgent OLT upon admission to the transplant center and
      underwent an urgent OLT. Their hemato-oncologic prognosis was considered to be
      favorable. All three patients are alive (54, 46, and 37 months post
      transplantation), tumor-free and HBsAg negative on a standard HBV prophylaxis
      regimen: hepatitis B immunoglobulin and LAM + adefovir or tenofovir. CONCLUSIONS:
      Before chemotherapy appropriate prophylaxis for HBV reactivation should always be
      administered to at-risk patients. However, if reactivation with FLF occurs, OLT
      should not be generally denied. The prognosis of the hematologic malignancy
      should be assessed; OLT should be considered for patients in remission with a
      favorable long-term prognosis, for our data suggest acceptable survival.

PMID- 24034062
TI  - Successful kidney and liver transplantation from a donor with immune
      thrombocytopenia.
AB  - Antibodies directed against platelet-surface antigen cause immune
      thrombocytopenia. Transplantation from a donor with immune thrombocytopenia has
      rarely been reported in the literature and never with a platelet count of 1 *
      10(9)/L. We report one liver transplant recipient and one kidney transplant
      recipient who received organs from a donor with immune thrombocytopenia dying
      from intracranial hemorrhage. The kidney recipient showed no evidence of
      thrombocytopenia after transplantation. However, in the liver recipient, the
      platelet count nadired at 4 * 10(9)/L and normalized within 3 months.
      Transplantation of a liver from a donor suffering from immune thrombocytopenia
      must be considered with great caution. Other organs are suitable for
      transplantation; however, recipients of these organs must be followed carefully
      for evidence of immune thrombocytopenia and treatment offered accordingly.

PMID- 24034063
TI  - Fludarabine, low-dose cyclophosphamide and rabbit antithymocyte globulin allowed
      stable engraftment after allogeneic peripheral blood stem cell transplantation
      for poly-transfused dyskeratosis congenita patient: case report.
AB  - BACKGROUND: Dyskeratosis congenita (DC) is characterized by the clinical triad of
      reticular skin pigmentation, oral leukoplakia, and nail dystrophy associated with
      bone marrow failure (BMF) and an high risk to develop cancer and pulmonary
      complications. The only curative treatment for patients with DC and BMF is stem
      cell transplantation. Due to the rarity of the disease, the best transplant
      procedure is not yet known. The use of myeloablative procedures has been
      associated with high mortality. In the last 2 decades, encouraging results have
      been obtained with nonmyeloablative procedures. Heavily transfused patients have
      an additional risk of graft failure. CASE REPORT: Herein we have reported a 4
      year-old boy with DC and severe BMF at the time of transplantation, who had been
      transfused with nonleucodepleted blood products for 18 months. He experienced a
      favorable outcome after nonmyeloablative transplant conditioning using low-dose
      cyclophosphamide (40 mg/kg), fludarabine (180 mg/kg), and rabbit antithymocyte
      globulin (10 mg/kg). The patient received a peripheral stem cell graft containing
      7.52 * 10(6) CD34/kg from an HLA identical sister. Graft versus host disease
      (GVHD) prophylaxis consisted of a short-term combination of cyclosporine and
      methotrexate. RESULTS: We observed rapid neutrophil engraftment on day +21 and
      for platelets on day +40. No early or late complications were recorded during 15
      months follow-up. The patient developed only grade I skin GVHD. On day +30,
      chimerism assay showed 100% donor cells. CONCLUSION: Long-term follow-up is
      essential to establish the efficacy and safety of this procedure.

PMID- 24034064
TI  - Successful treatment of both acute leukemia and active Crohn's disease after
      allogeneic hematopoietic stem cell transplantation using reduced-intensity
      conditioning with fludarabine and busulfan: a case report.
AB  - BACKGROUND: A 32-year-old man diagnosed with acute myelomonocytic leukemia (M4)
      concurrently had active Crohn's disease (CD) that was refractory to azathioprine
      and anti-tumor necrosis factor. CASE REPORT: He underwent an allogeneic bone
      marrow transplantation from a one HLA-DR allele-mismatched unrelated donor to
      achieve the first complete remission of leukemia. The conditioning regimen
      consisted of fludarabine (180 mg/m(2)) and busulfan (8.0 mg/kg) without T-cell
      depletion. Graft-versus-host disease (GVHD) prophylaxis included tacrolimus and
      mycophenolate mofetil. Cefotaxime was prescribed for a secondary bacterial
      infection in a perianal abscess before the start of conditioning chemotherapy.
      Although low-grade diarrhea persisted, there were no signs of either acute GVHD
      or CD in the mucosal biopsy specimens on day 24. Complete remission of leukemia
      and near remission of CD were sustained for 20 months after transplantation
      without any immunosuppressive drug. CONCLUSIONS: Allogeneic heamtopoietic stem
      cell transplantation with reduced-intensity conditioning is a possible
      therapeutic option for patients with severe and/or refractory CD.

PMID- 24034065
TI  - Screening of drug target proteins by 2D ligand matching approach.
AB  - Drugs interacting with off-target proteins would bring about side-effects. The
      identification of the proteins that a drug can bind is thus valuable for
      evaluating its side-effects. We established a system based on PDB database for
      screening for proteins a drug could bind. Firstly, all complexes in the PDB
      database were sorted by species; then, a ligand database was established by
      extracting ligands from the structure data files. Secondly, all proteins were
      clustered according to their sequence similarity with the protein originally
      bound with the ligand in PDB. To search the potential target proteins of a drug,
      the query drug structure is compared with all ligands in the database to obtain
      similar scores. Ligands with similar sores greater than a certain threshold were
      flagged. Protein clusters associating with these ligands would be considered as
      potential targets of the query drug. To test the reliability of this approach,
      three drugs from DrugBank were used to search for their binding proteins by our
      method. The results showed that all the corresponding target proteins were found.
      The method presented here was rapid, scalable and could be used for high
      efficient drug side-effects analysis. 

PMID- 24034066
TI  - Update on oral fungal infections.
AB  - The incidence of oral fungal infections has increased in recent years as a result
      of factors such as increased number of solid organ transplantations and the
      widespread use of immunosuppressive drug therapies. This article reviews the
      diagnosis and treatment of oral fungal infections. At one time oral fungal
      infections were a relatively uncommon event, but with advances in health care and
      polypharmacy in an increasingly aging population, these infections are becoming a
      more routine clinical finding. The dental practitioner therefore needs to be
      familiar with the diagnosis and management of oral fungal infections. 

PMID- 24034067
TI  - Erythema multiforme: a review of epidemiology, pathogenesis, clinical features,
      and treatment.
AB  - Erythema multiforme (EM) is an acute, immune-mediated disorder affecting the skin
      and/or mucous membranes, including the oral cavity. Target or iris lesions
      distributed symmetrically on the extremities and trunk characterize the
      condition. Infections are the most common cause of EM and the most frequently
      implicated infectious agent causing clinical disease is the herpes simplex virus.
      The diagnosis of EM is typically based on the patient's history and clinical
      findings. Management involves controlling the underlying infection or causative
      agent, symptom control, and adequate hydration. The epidemiology, pathogenesis,
      clinical features, diagnosis, and treatment of EM are reviewed in this article. 

PMID- 24034068
TI  - Pemphigus.
AB  - Pemphigus vulgaris and paraneoplastic pemphigus are 2 subtypes of pemphigus that
      involve the oral mucosa. These autoimmune blistering disorders have antibodies
      targeted against proteins of keratinocyte adhesion, thereby causing acantholysis.
      Clinical findings include oral erosions and flaccid cutaneous bullae and
      erosions. Further malignancy workup in patients with suspected paraneoplastic
      pemphigus is warranted. Retrospective uncontrolled studies suggest that
      immunosuppressive agents reduce mortality in pemphigus vulgaris and cohort
      uncontrolled studies of rituximab, a monoclonal antibody against CD20, suggest it
      is an effective treatment for refractory patients. Ongoing studies will define
      its role in early disease. 

PMID- 24034070
TI  - Systemic lupus erythematosus: epidemiology, pathophysiology, manifestations, and
      management.
AB  - Systemic lupus erythematosus is a chronic autoimmune disorder characterized by
      production of autoantibodies directed against nuclear and cytoplasmic antigens,
      affecting several organs. Although cause is largely unknown, pathophysiology is
      attributed to several factors. Clinically, this disorder is characterized by
      periods of remission and relapse and may present with various constitutional and
      organ-specific symptoms. Diagnosis is achieved via clinical findings and
      laboratory examinations. Therapies are based on disease activity and severity.
      General treatment considerations include sun protection, diet and nutrition,
      smoking cessation, exercise, and appropriate immunization, whereas organ-specific
      treatments include use of steroidal and nonsteroidal anti-inflammatory drugs,
      immunosuppressive agents, and biologic agents. 

PMID- 24034069
TI  - Mucous membrane pemphigoid.
AB  - Mucous membrane pemphigoid (MMP) is chronic and frequently associated with
      exacerbations and remissions of clinical signs and symptoms. Clinicians should
      use pathologic and immunonologic techniques to help diagnose patients.
      Multidisciplinary collaboration is often necessary for the diagnosis and proper
      treatment of MMP. Systemic adjuvant immunosuppressive therapy is necessary for
      patients with progressive disease. In spite of the advances in available
      immunosuppressive medications and biologics, scarring is a significant
      complication in many cases. Surgical intervention is not curable; however, it may
      be necessary for restoring function and improving quality of life. 

PMID- 24034071
TI  - An update on granulomatous diseases of the oral tissues.
AB  - With new insights into the pathogenesis of specific granulomatous diseases, and
      with the advent of high-throughput genetic screening and availability of next
      generation biological therapies, clinicians have several options at their
      disposal to help ensure accurate diagnosis and effective treatment. This article
      highlights some of the current knowledge about the more common granulomatous
      systemic diseases that may be encountered in clinical practice. 

PMID- 24034072
TI  - Oral lesions associated with human immunodeficiency virus disease.
AB  - Human immunodeficiency virus (HIV)-associated oral disease among people living
      with HIV infection includes oral candidiasis, oral hairy leukoplakia, Kaposi
      sarcoma, oral warts, herpes simplex virus ulcers, major aphthous ulcers or ulcers
      not otherwise specified, HIV salivary gland disease, and atypical gingival and
      periodontal diseases. Diagnosis of some oral lesions is based on clinical
      appearance and behavior, whereas others require biopsy, culture, or imaging for
      definitive diagnosis. Management strategies including pharmacologic and
      nonpharmacologic approaches are discussed in this article. Dentists also need to
      be cognizant of the potential oral side effects of HIV antiretroviral
      medications. 

PMID- 24034073
TI  - Pigmented lesions of the oral cavity: an update.
AB  - Oral pigmentation may be focal, multifocal, or diffuse. The lesions may be blue,
      purple, brown, gray, or black. They may be macular or tumefactive. Some are
      localized harmless accumulations of melanin, hemosiderin, or exogenous metal;
      others are harbingers of systemic or genetic disease; and some can be associated
      with life-threatening medical conditions that require immediate intervention. The
      differential diagnosis for any pigmented lesion is extensive, and can include
      examples of endogenous and exogenous pigmentation. Although biopsy is a helpful
      and necessary aid in the diagnosis of focally pigmented lesions, with diffuse
      presentations lesions require a thorough history and laboratory studies to
      establish a definitive diagnosis. 

PMID- 24034074
TI  - Clinical approaches to oral mucosal disorders.

PMID- 24034075
TI  - Molecular characterization of TaSTOP1 homoeologues and their response to
      aluminium and proton (H(+)) toxicity in bread wheat (Triticum aestivum L.).
AB  - BACKGROUND: Aluminium (Al) toxicity is considered to be one of the major
      constraints affecting crop productivity on acid soils. Being a trait governed by
      multiple genes, the identification and characterization of novel transcription
      factors (TFs) regulating the expression of entire response networks is a very
      promising approach. Therefore, the aim of the present study was to clone,
      localize, and characterize the TaSTOP1 gene, which belongs to the zinc finger
      family (Cys2His2 type) transcription factor, at molecular level in bread wheat.
      RESULTS: TaSTOP1 loci were cloned and localized on the long arm of homoeologous
      group 3 chromosomes [3AL (TaSTOP1-A), 3BL (TaSTOP1-B) and 3DL (TaSTOP1-D)] in
      bread wheat. TaSTOP1 showed four potential zinc finger domains and the
      homoeologue TaSTOP1-A exhibited transactivation activity in yeast. Expression
      profiling of TaSTOP1 transcripts identified the predominance of homoeologue
      TaSTOP1-A followed by TaSTOP1-D over TaSTOP1-B in root and only predominance of
      TaSTOP1-A in shoot tissues of two diverse bread wheat genotypes. Al and proton
      (H(+)) stress appeared to slightly modulate the transcript of TaSTOP1
      homoeologues expression in both genotypes of bread wheat. CONCLUSIONS: Physical
      localization of TaSTOP1 results indicated the presence of a single copy of
      TaSTOP1 on homoeologous group 3 chromosomes in bread wheat. The three
      homoeologues of TaSTOP1 have similar genomic structures, but showed biased
      transcript expression and different response to Al and proton (H(+)) toxicity.
      These results indicate that TaSTOP1 homoeologues may differentially contribute
      under Al or proton (H(+)) toxicity in bread wheat. Moreover, it seems that
      TaSTOP1-A transactivation potential is constitutive and may not depend on the
      presence/absence of Al at least in yeast. Finally, the localization of TaSTOP1 on
      long arm of homoeologous group 3 chromosomes and the previously reported major
      loci associated with Al resistance at chromosome 3BL, through QTL and genome wide
      association mapping studies suggests that TaSTOP1 could be a potential candidate
      gene for genomic assisted breeding for Al tolerance in bread wheat.

PMID- 24034076
TI  - Campylobacter jejuni and cytopenias.
AB  - BACKGROUND: Leukopenia and thrombocytopenia in a febrile patient are not uncommon
      and may be a diagnostic clue in patients without an alternative explanation for
      cytopenias. This has not been reported in Campylobacter jejuni infections.
      METHODS: A healthy patient with fever, rigors, and an acute diarrheal illness was
      noted to have a white blood cell count of 2.65 * 10(9)/L and platelet level of
      125 * 10(9)/L. Retrospective chart review of all adult C. jejuni stool-positive
      cases admitted over 1 year revealed leukopenia in 6 of 20 (30%), thrombocytopenia
      in 5 of 20 (25%), and both in 1 of 20 (5%). RESULTS: Cytopenias were mild,
      transient, and not associated with prolonged hospital stay or complications.
      CONCLUSIONS: Acute C. jejuni infections should be added to the differential
      diagnosis of acute febrile illnesses that may be associated with leukopenia or
      thrombocytopenia. Cytopenias can be an important diagnostic clue in febrile
      illnesses, and their differential is presented.

PMID- 24034078
TI  - Treatment for acute ischemic stroke: new evidence from China.

PMID- 24034077
TI  - Public health services knowledge and utilization among immigrants in Greece: a
      cross-sectional study.
AB  - BACKGROUND: During the 90s, Greece has been transformed to a host country for
      immigrants mostly from the Balkans and Eastern European Countries, who currently
      constitute approximately 9% of the total population. Despite the increasing
      number of the immigrants, little is known about their health status and their
      accessibility to healthcare services. This study aimed to explore the perceived
      barriers to access and utilization of healthcare services by immigrants in
      Greece. METHODS: A pilot cross-sectional study was conducted from January to
      April 2012 in Athens, Greece. The study population consisted of 191 immigrants
      who were living in Greece for less than 10 years. We developed a questionnaire
      that included information about sociodemographic characteristics, health status,
      public health services knowledge and utilization and difficulties in health
      services access. Statistical analysis included Pearson's *2 test, *2 test for
      trend, Student's t-test, analysis of variance and Pearson's correlation
      coefficient. RESULTS: Only 20.4% of the participants reported that they had a
      good/very good degree of knowledge about public health services in Greece. A
      considerable percentage (62.3%) of the participants needed at least once to use
      health services but they could not afford it, during the last year, while 49.7%
      used public health services in the last 12 months in Greece. Among the most
      important problems were long waiting times in hospitals, difficulties in
      communication with health professionals and high cost of health care. Increased
      ability to speak Greek was associated with increased health services knowledge
      (p<0.001). Increased family monthly income was also associated with less
      difficulties in accessing health services (p<0.001). CONCLUSIONS: The empowerment
      and facilitation of health care access for immigrants in Greece is necessary.
      Depending on the needs of the migrant population, simple measures such as
      comprehensive information regarding the available health services and the terms
      for accessibility is an important step towards enabling better access to needed
      services.

PMID- 24034079
TI  - Ninety-day administration of dl-3-n-butylphthalide for acute ischemic stroke: a
      randomized, double-blind trial.
AB  - BACKGROUND: Dl-3-n-butylphthalide (NBP), first isolated from the seeds of celery,
      showed efficacy in animal models of stroke. This study was a clinical trial to
      assess the efficacy and safety of NBP with a continuous dose regimen among
      patients with acute ischemic stroke. METHODS: A randomized, double-blind, double
      dummy trial enrolled 573 patients within 48 hours of onset of ischemic stroke in
      China. Patients were randomly assigned to receive a 14-day infusion of NBP
      followed by an NBP capsule, a 14-day infusion of NBP followed by aspirin, or a 14
      day infusion of ozagrel followed by aspirin. The efficacy measures were Barthel
      index score and the modified Rankin scale (mRS) at day 90. Differences among the
      three groups on mRS were compared using chi(2) test of proportions (with two
      sided alpha = 0.05) and Logistic regression analysis was conducted to take the
      baseline National Institutes of Health Stroke Scale (NIHSS) score into
      consideration. RESULTS: Among the 535 subjects included in the efficacy analysis,
      90-day treatment with NBP was associated with a significantly favorable outcome
      than 14-day treatment with ozagrel as measured by mRS (P < 0.001). No significant
      difference was found among the three groups on Barthel index at day 90. The rate
      of adverse events was similar among the three groups. CONCLUSIONS: The 90-day
      treatment with NBP could improve outcomes at the third month after stroke. The
      NBP treatment (both intravenous and oral) is safe (ChiCTR-TRC-09000483).

PMID- 24034080
TI  - Neurological deterioration in the acute phase of minor ischemic stroke is an
      independent predictor of poor outcomes at 1 year: results from the China National
      Stroke Registry (CNSR).
AB  - BACKGROUND: The risk of clinical deterioration still exists in the acute phase
      despite the fact that patients with minor stroke may display less severe
      symptoms. The impact of this clinical deterioration on long-term outcomes is
      unknown. We characterized the clinical features of neurological deterioration
      (ND) in the acute phase of minor ischemic stroke (MIS) and investigated its
      impact on mid- and long-term outcomes. METHODS: This was a multi-centered,
      prospective clinical study involving patients with MIS (the National Institutes
      of Health Stroke Scale, NIHSS <=3) recruited from the China National Stroke
      Registry. Patients were included who had been hospitalized within 24 hours of
      stroke onset. Baseline characteristics, complication rates during
      hospitalization, etiology of stroke, as well as 3-, 6-, and 12-month post-stroke
      outcomes were compared between patients with and without ND during the acute
      phase. RESULTS: A number of 368 (15.2%) out of 2424 patients included in the
      study exhibited ND in the acute phase. Compared to patients without ND, patients
      with ND had longer hospital stay, increased rate of baseline diabetes, and
      multiple complications. Multivariate Logistic regression indicated that ND in
      acute phase was an independent factor predictive of increased dependence
      (adjusted odds ratio = 5.20, 95% CI, 3.51-7.70, P < 0.001) at 12-month post
      stroke. CONCLUSIONS: The risk of ND in the acute phase is high in patients with
      MIS. ND in the acute phase is an independent predictor for poor outcomes at 12
      months post-stroke onset.

PMID- 24034081
TI  - Psychological distress, family functioning, and social support in family
      caregivers for patients with dementia in the mainland of China.
AB  - BACKGROUND: Dementia is a chronic progressive disease seriously affecting the
      patient's daily life and working skills and may cause the patient disability and
      dependence. Thus, caring for dementia patients inevitably falls on families in
      the mainland of China. Unfortunately, there are rarely enough reports available
      about mental health and social support in family caregivers for domestic dementia
      patients. This study aimed to investigate the changes in psychological status and
      social support in domestic dementia family caregivers and hope the government and
      relevant departments pay more attention to the family caregiver's psychological
      change, which may be better for dementia patients. METHODS: Fifty-eight immediate
      family caregivers (family group) for dementia patients, including 21 Alzheimer's
      disease (AD) and 37 vascular dementia inpatients, were recruited for interview.
      Fifty-eight age- and sex-matched normal volunteers (control group) were also
      interviewed in the same period. The psychiatric distress was assessed by the
      Symptom Checklist 90 (SCL-90), family functioning was assessed by the Family
      Assessment Device (FAD), and the social support was assessed by the
      Multidimensional Scale of Perceived Social Support (MSPSS). Group differences
      were analyzed using unpaired t test for comparison of SCL-90, FAD, and MSPSS mean
      scores. Pearson's correlation coefficient was used to find the association
      between the various dimensions of FAD and the social support from dementia family
      caregivers. RESULTS: Except phobic anxiety dimension, the other dimensions of SCL
      90 mean scores were significantly higher in the family group than those in the
      control group (P < 0.05). In the family group, except affective involvement
      dimension, the other dimensions of FAD mean scores were within the scope of
      unhealthy family functioning. Significant differences in problem solving,
      communication, roles, affective responsiveness, behavioral control, general
      functioning, and the total MSPSS mean scores were seen between the family group
      and the control group (P < 0.01). Except affective involvement dimension, the
      other dimensions of the family functioning correlated with the perceived social
      support in the family group (P < 0.05 or 0.01). CONCLUSIONS: Dementia patients
      have a negative effect on families' mental health in the mainland of China.
      Dementia family caregivers experience defected family functioning and low levels
      of social support.

PMID- 24034082
TI  - An overview of neurocritical care in China: a nationwide survey.
AB  - BACKGROUND: Little quantitative evidence was available regarding the development
      of NICUs in China. The purpose of this survey was to evaluate the current
      situation of neurointensive care units (NICUs) across China. METHODS: The
      directors of NICUs from 100 tertiary care hospitals across China were contacted
      and asked to complete a closed response questionnaire regarding their NICUs.
      Basic information, equipment, and technology information available in the units,
      as well as staffing information were investigated. RESULTS: Seventy-six
      questionnaires were returned (a 68% response rate). Of 76 NICUs, 43 units
      constituted the majority. The number of each NICU bed varied from 4 to 45,
      occupying 2%-30% of the total department beds. Over 70% of NICUs were equipped
      with many emergency treatment equipments as well as physiological and biochemical
      monitoring equipments, while 34%-70% of NICUs still lacked some kinds of
      equipments such as defibrillators. Some specialist equipments were still
      partially lacking in 62%-95% of NICUs. A vast majority of the NICUs were equipped
      with neurocritical care directors, full-time attending physicians, and head
      nurses, but full-time NICU residents and neurocritical care nurses were still
      lacking in nearly half (53%) and one-third (33%-37%) of NICUs, respectively. In
      76 NICUs, full-time neurointensivists and nurses added up to 359 and 852,
      respectively. In addition, 78%-97% of all the surveyed NICUs were severely short
      of non-neurological professional staffs. CONCLUSION: In China, neurocritical care
      has developed rapidly, but there is still a shortage of well-equipped and well
      staffed NICUs across the nation currently.

PMID- 24034083
TI  - Features of a Chinese family with cerebral cavernous malformation induced by a
      novel CCM1 gene mutation.
AB  - BACKGROUND: Familial cerebral cavernous malformations (CCMs), characterized by
      hemorrhagic stroke, recurrent headache and epilepsy, are congenital vascular
      anomalies of the central nervous system. Familial CCMs is an autosomal dominant
      inherited disorder and three CCM genes have been identified. We report a Chinese
      family with CCMs and intend to explore clinical, pathological, magnetic resonance
      imaging (MRI) features and pathogenic gene mutation of this family. METHODS:
      Totally 25 family members underwent brain MRI examination and clinical check. Two
      patients with surgical indications had surgical treatment and the specimens were
      subjected to histopathological and microstructural examination. In addition,
      polymerase chain reaction (PCR) and direct sequencing were performed with genomic
      DNA extracted from 25 family members' blood samples for mutation detection.
      RESULTS: Brain MRI identified abnormal results in seven family members. All of
      them had multiple intracranial lesions and four cases had skin cavernous
      hemangioma. T2-weighted sequence showed that the lesions were typically
      characterized by an area of mixed signal intensity. Gradient-echo (GRE) sequence
      was more sensitive to find micro-cavernous hemangiomas. There was a wide range in
      the clinical manifestations as well as the age of onset in the family. The
      youngest patient was an 8-year-old boy with least intracranial lesions.
      Histopathological and microstructural examination showed that CCMs were typically
      discrete multi-sublobes of berry-like lesions, with hemorrhage in various stages
      of illness evolution. They were formed by abnormally enlarged sinusoids and the
      thin basement membranes. A novel T deletion mutation in exon 14 of CCM1 gene was
      identified by mutation detection in the seven patients. But unaffected members
      and healthy controls did not carry this mutation. CONCLUSIONS: The clinical
      manifestations were heterogenic within this family. We identified a novel
      mutation (c.1396delT) was the disease-causing mutation for this family and
      extended the mutational spectrum of CCMs.

PMID- 24034084
TI  - Isolated medial rectus palsy.

PMID- 24034085
TI  - Perihematomal endothelin-1 level is associated with an increase in blood-brain
      barrier permeability in a rabbit model of intracerebral hematoma.
AB  - BACKGROUND: Endothelin-1 (ET-1) has deleterious effects on water homeostasis,
      cerebral edema, and blood-brain barrier (BBB) integrity. Highly expressed ET-1
      was observed after intracerebral hemorrhage (ICH); however, ET-1 changes and
      their relationship with BBB disruption within 24 hours of ICH have not been
      thoroughly investigated. The aim of the present study was to observe the changes
      in perihematomal ET-1 levels in various phases of ICH and their correlation with
      the BBB integrity in a rabbit model of ICH. METHODS: Twenty-five rabbits (3.2-4.3
      kg body weight) were randomly divided into a normal control group (five rabbits)
      and a model group (20 rabbits). Animals in the model group were equally divided
      into four subgroups (five rabbits each to be sacrificed at 6, 12, 18, and 24
      hours following ICH establishment). An ICH model was prepared in the model group
      by infusing autologous arterial blood into the rabbit brain. ET-1 expression in
      perihematomal brain tissues was determined using immunohistochemistry and color
      image analysis, and the permeability of the BBB was assayed using the Evan's Blue
      (EB) method. A repeated measures analysis of variance was used to make
      comparisons of the ET-1 and EB content across the entire time series. RESULTS:
      The number of perihematomal endothelial cells with ET-1 positive expressions
      following 6, 12, 18, and 24 hours ICH model establishment was 9.32, 13.05, 15.90,
      and 20.44, respectively, but as low as 6.67 in the control group. The average
      transmittance of ET-1-positive cell bodies at 6, 12, 18, and 24 hours after ICH
      was 99.10, 97.40, 85.70, and 80.80, respectively, but 100.12 in the control
      group. These data reveal that the expression of ET-1 was significantly increased
      at 6, 12, 18, and 24 hours after ICH compared with the control group, and a
      marked decrease in the average transmittance of ET-1-positive cell bodies was
      noted (P < 0.05). Similarly, the perihematomal EB content at 6, 12, 18, and 24
      hours after ICH was 29.39 +/- 1.16, 32.20 +/- 0.73, 33.63 +/- 1.08, and 35.26 +/-
      1.12, respectively, in the model group and 28.06 +/- 0.80 in the control group.
      The results indicate that a significant increase in the EB content in the model
      group was observed compared with that of the control group (P < 0.05). Moreover,
      a positive correlation between the number of ET-1-positive endothelial cells and
      BBB permeability was observed (r = 0.883, P < 0.05). CONCLUSIONS: High levels of
      ET-1 are closely associated with BBB disruption. ET-1 may play an important role
      in the pathogenesis of secondary brain injury after ICH.

PMID- 24034086
TI  - Combined therapy with methylprednisolone and ulinastatin in experimental
      autoimmune encephalomyelitis.
AB  - BACKGROUND: Our previous study had demonstrated that ulinastatin (UTI) had a
      neuroprotective effect in experimental autoimmune encephalomyelitis (EAE).
      Methylprednisolone has been recommended to be a standard drug in multiple
      sclerosis (MS) therapies. The present study was to investigate the protective
      effects of UTI combined methylprednisolone in EAE. METHODS: Mice were divided
      into a UTI treatment group, a methylprednisolone treatment group, a combined
      treatment group with UTI and methylprednisolone, a normal saline treatment group,
      and a normal control group. EAE mice were induced in groups receiving different
      combined treatments, or respective monotherapies. Demyelination was evaluated by
      Solochrome cyanin staining. 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP)/
      myelin basic protein (MBP)/ the precursor form of nerve growth factor
      (proNGF)/p75/ inducible nitric oxide synthase (iNOS) proteins in cerebral cortex
      of EAE were detected by Western blotting. RESULTS: The combined treatment group
      had a lower clinical score (0.61 +/- 0.06) and demyelinating score (1.33 +/-
      0.33) than the groups with normal saline (clinical score: 1.39 +/- 0.08, P <
      0.001; demyelinating score: 2.75 +/- 0.49, P < 0.05) or monotheraphies. Compared
      with the saline treated EAE group, UTI combined methylprednisolone significantly
      increased expressions of CNP (1.14 +/- 0.06 vs. 0.65 +/- 0.04, P < 0.001), MBP
      (1.28 +/- 0.14 vs. 0.44 +/- 0.17, P < 0.001), and decreased expressions of proNGF
      (1.08 +/- 0.10 vs. 2.32 +/- 0.12, P < 0.001), p75 (1.13 +/- 0.13 vs. 2.33 +/-
      0.17, P < 0.001), and iNOS (1.05 +/- 0.31 vs. 2.17 +/- 0.13, P < 0.001) proteins
      in EAE. Furthermore, UTI combined methylprednisolone could significantly
      upregulate MBP (1.28 +/- 0.14 vs. 1.01 +/- 0.15, P < 0.05) expression and
      downregulate iNOS (1.05 +/- 0.31 vs. 1.35 +/- 0.14, P < 0.05) expression compared
      to methylprednisolone treatment EAE group. And proNGF expression was
      significantly lower in combined treatment (1.08 +/- 0.10) than that in UTI (1.51
      +/- 0.24, P < 0.05) or methylprednisolone (1.31 +/- 0.04, P < 0.05) treatment
      group. CONCLUSION: Combination treatment of UTI with methylprednisolone was shown
      to protect EAE, suggesting that combination therapy is a potential novel
      treatment in MS.

PMID- 24034087
TI  - A single-site retrospective study of pediatric arterial ischemic stroke etiology,
      clinical presentation, and radiologic features.
AB  - BACKGROUND: Stroke occurs upon obstruction of cerebral blood circulation and is
      clinically characterized by sudden onset symptoms. Advanced age is the main risk
      factor of stroke, but cases of pediatric stroke have been rarely reported. This
      study aimed to determine the etiology, clinical presentation, and radiologic
      features of neurological deficit for pediatric arterial ischemic stroke (PAIS).
      METHODS: The medical records of 42 PAIS patients (age range: 9 months to 13
      years) treated at Wuhan Children's Hospital between July 2007 and January 2011
      were retrospectively reviewed. Infarction location was first determined by
      craniocerebral computed tomography and magnetic resonance (MR) imaging. The
      stenotic or occluded main cerebral arteries and/or branches were determined by MR
      angiography and digital subtraction angiography. RESULTS: The majority of the 42
      PAIS cases (66.7%, n = 28) were <= 3 years old (vs. >3 years old: 33.3%, n = 14;
      P<0.05), but the male: female ratio was similar in both groups (P > 0.05). The
      most frequently reported signs and symptoms for both age groups were limited
      physical activity followed by convulsions and delirium, but convulsions were more
      prevalent in children <= 3 years-old. Children > 3 years-old mainly experienced
      the limited physical activity symptoms, including hemiparalysis, aphasia, and
      ataxia. For all 42 cases, the most frequent etiologies were infections (38.1%, n
      = 16), iron deficiency anemia (16.7%, n = 7), and moyamoya syndrome (11.9%, n =
      5). The predominant infarcts among all cases were middle cerebral artery (63.6%,
      n = 21) and basal ganglia (64.3%, n = 27). CONCLUSIONS: PAIS occurs more
      frequently in younger children and this group most frequently presents with
      convulsion as the initial symptom. The overall etiologies of PAIS may be
      different from those of adult stroke and the involved regions may be
      distinguishing features of PAIS or its different forms, but more research is
      required.

PMID- 24034088
TI  - National survey of doctor-reported secondary preventive treatment for patients
      with acute coronary syndrome in China.
AB  - BACKGROUND: Long-term use of antiplatelet agents, statins, beta-blockers and
      angiotensin-converting enzyme inhibitors are proven therapies for secondary
      prevention in acute coronary syndrome. However, little is known of physicians'
      opinion about their use in China. METHODS: In 2010, standard questionnaires were
      posted to chief cardiologists in 1397 geographically diverse and representative
      sample of tertiary and secondary hospitals in China, collecting information about
      their opinions on the recommended treatments for acute coronary syndrome.
      RESULTS: A total of 1009 (72%) cardiologists responded with a valid
      questionnaire. Of them, 77% reported routine use of all the four main secondary
      preventive treatments, with little difference between secondary and tertiary
      hospitals (75% vs. 79%, P = 0.16). Of the cardiologists reporting routine or
      selective use of aspirin, beta-blockers, statins and angiotensin-converting
      enzyme inhibitors, 94%, 85%, 73% and 86% would recommend indefinite use
      respectively. For all the 4 treatments combined, only 63.5% reported indefinite
      use at the same time, with no significant difference between secondary and
      tertiary hospitals (62% vs. 65%, P = 0.17), nor between hospitals with or without
      fast track for primary percutaneous coronary intervention (66% vs. 61%, P =
      0.50). CONCLUSIONS: Although Chinese cardiologists seem well informed about the
      value of main secondary preventive treatments for acute coronary syndrome, there
      is still gap in their understanding of the need for combined and prolonged use of
      these treatments.

PMID- 24034089
TI  - Initial experience of occluding special type patent ductus arterioses using the
      Amplatzer vascular plug.
AB  - BACKGROUND: Occluders licensed for clinical use are not fit for some special
      Krichenko E patent ductus arterioses. The Amplatzer vascular plug I (AVP1) has
      not been licensed for use for closure of patent ductus arteriose. We report our
      initial experience to occluding special type patent ductus arterioses with the
      AVP1-a single lobe device of single layer Nitinol mesh for short vessel landing
      zones. METHODS: Patients referred with small and long Krichenko E patent ductus
      arterioses 1 mm to 3 mm in diameter underwent occlusion using AVP1. All cases
      underwent pre-, intra- and post-procedural echocardiography and chest X-ray at
      the completion of the procedure, the next day and at a 30-day, 3-month and 6
      month follow-up visits. Device sizing for device waist diameter and length was
      based on aortography. RESULTS: From April 2008 to June 2012, 26 patients with a
      mean age of (7.6 +/- 8.0) years (range 6 months-32 years) and a mean weight of
      (23.8 +/- 14.8) kg (range 7-67 kg) underwent successful patent ductus arteriose
      closure. The mean ductus diameter was (2.1 +/- 0.7) mm (range 1-3 mm).
      Transpulmonary (22/26) and transaortic approaches (4/26) were used. No persistent
      patency was observed after 24 hours and after one month. No device displacement,
      residual flow and iatrogenic coarctation of the aorta were observed after three
      months and six months. CONCLUSIONS: The AVP1 makes it easy to close some
      Krichenko E patent ductus arterioses. Smaller delivery catheter profile and
      symmetric cylindrical device shape allow for use for small and long Krichenko E
      patent ductus arterioses 1 mm to 3 mm in diameter and small patients through
      transaortic approaches. Broader experience is required to further delineate
      device and patient selection as well as to document its long-term efficacy and
      safety.

PMID- 24034090
TI  - Heart rate distribution and predictors of resting heart rate after initiation of
      beta-blocker treatment in patients with coronary artery disease: REsults of
      Sympathetic Evaluation And Research of China (RESEARCH) study.
AB  - BACKGROUND: The importance of heart rate as secondary prevention strategies for
      patients with coronary artery disease (CAD) is emphasized by multiple guidelines.
      However, limited information is available on the heart rate distribution and the
      change patterns of resting heart rate when initiating beta-blocker therapy among
      Chinese patients with CAD. METHODS: The REsults of Sympathetic Evaluation And
      Research of China (RESEARCH) study is a multi-centre, prospective, observational
      study involving 147 centers in 23 cities across China. All eligible beta-blocker
      naive patients were prescribed with metroprolol succinate. Initial dosage and
      target heart rate were selected at the discretion of their physicians in charge
      according to their usual institutional practice. The heart rate distribution and
      the change patterns of resting heart rate after initiation of beta-blocker
      therapy were observed. RESULTS: The majority of patients (63.6%) were prescribed
      with 47.5 mg metroprolol succinate. At baseline, there were only 17.4% of
      patients whose heart rate was less than 70 beats per minute, and the proportion
      reached 42.5% and 79.1%, one month and two months after initiation of beta
      blockers, respectively. Multivariate linear regression analysis showed that
      baseline heart rate (B = 0.900, SE = 0.006, t = 141.787, P < 0.0001) and the
      dosage (B = -0.007, SE = 0.002, t = -3.242, P = 0.001) were independent
      predictors of resting heart rate 2 months after beta-blocker therapy.
      CONCLUSIONS: Resting heart rate is not optimally controlled in a broadly
      representative cohort of Chinese outpatients with CAD even after initiation of
      beta-blocker therapy, and baseline heart rate and the dosage of beta-blocker are
      both independent predictors of resting heart rate after beta-blocker therapy.

PMID- 24034091
TI  - Risk factors for perioperative major cardiac events in Chinese elderly patients
      with coronary heart disease undergoing noncardiac surgery.
AB  - BACKGROUND: Few studies have investigated perioperative major adverse cardiac
      events (MACEs) in elderly Chinese patients with coronary heart disease (CHD)
      undergoing noncardiac surgery. This study examined the incidence and risk factors
      for perioperative MACE in elderly patients who underwent noncardiac surgery, and
      established a risk stratification system. METHODS: This retrospective
      observational clinical study included 482 patients aged >=60 years with CHD who
      underwent elective major noncardiac surgery at the Peking Union Medical College
      Hospital. The primary outcome was MACE within 30 days after surgery. Risk factors
      were evaluated using multivariate Logistic regression analysis. RESULTS:
      Perioperative MACE occurred in 61(12.66%) of the study patients. Five independent
      risk factors for perioperative MACE were identified: history of heart failure,
      preoperative arrhythmia, preoperative diastolic blood pressure <=75 mmHg,
      American Society of Anesthesiologists grade 3 or higher, and intraoperative blood
      transfusion. The area under the receiver operating characteristic curve for the
      risk-index score was 0.710+/-0.037. Analysis of the risk stratification system
      showed that the incidence of perioperative MACE increased significantly with
      increasing levels of risk. CONCLUSIONS: Elderly Chinese patients with CHD who
      undergo noncardiac surgery have a high risk of perioperative MACE. Five
      independent risk factors for perioperative MACE were identified. Our risk
      stratification system may be useful for assessing perioperative cardiac risk in
      elderly patients undergoing noncardiac surgery.

PMID- 24034092
TI  - A phase II trial of oxaliplatin plus S-1 as a first-line chemotherapy for
      patients with advanced gastric cancer.
AB  - BACKGROUND: Palliative chemotherapy has been shown to have a survival benefit for
      patients with recurrent or metastatic gastric cancer. We conducted a Phase II
      trial to determine the efficacy and safety of S-1 plus oxaliplatin (SOX regimen)
      as first-line chemotherapy for patients with unresectable locally advanced or
      metastatic gastric cancer. METHODS: Eligible patients had measurable lesions and
      no previous history of chemotherapy (except adjuvant chemotherapy). Oxaliplatin
      was administered intravenously at a dose of 130 mg/m(2) on day 1. S-1 was
      administered orally in doses of 80, 100, or 120 mg/d according to body surface
      areas of <1.25 m(2), 1.25-1.5 m(2), or >1.5 m(2) respectively; the total dose was
      divided into two daily doses on days 1-14. Treatments were repeated every 3 weeks
      until disease progression or intolerable toxicity occurred. RESULTS: Forty-three
      patients were enrolled in the study. All were assessable for efficacy and adverse
      events. The objective response and disease control rates were 55.8% and 76.7%
      respectively. The median follow-up time was 16.5 months. The median progression
      free survival time was 7 months (95% CI, 5.8-8.2 months) and the median overall
      survival time was 16.5 months (95% CI, 9.7-23.3 months). The one-year survival
      rate was 54.2%. Major adverse reactions were grade 3/4 neutropenia (9.3%) and
      thrombocytopenia (20.9%). CONCLUSION: The SOX regimen with oxaliplatin at a dose
      of 130 mg/m(2) was found to be effective and safe as a first-line chemotherapy in
      Chinese patients with advanced gastric cancer.

PMID- 24034093
TI  - Renoprotective effect of alprostadil in combination with statins in patients with
      mild to moderate renal failure undergoing coronary angiography.
AB  - BACKGROUND: The role of alprostadil and statins in contrast-induced acute kidney
      injury (CI-AKI) is controversial. The purpose of this study was to explore the
      efficacy of combined therapy with alprostadil and statins in protecting renal
      function and preventing contrast-induced nephropathy (CIN) in patients undergoing
      coronary angiography. METHODS: A total of 156 consecutive patients with mild to
      moderate renal failure who underwent coronary angiography were enrolled in our
      study, and randomly categorized into two groups. In the statins group, 80
      patients were treated with statins before and after coronary angiography. In the
      alprostadil plus statins group, 76 patients were treated with statins and
      alprostadil before and after coronary angiography. Serum creatinine (SCr), serum
      cystatin (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) were
      detected after administration of contrast media, and adverse events were
      evaluated within six months. RESULTS: In both groups, the SCr, CysC and NGAL
      significantly increased after coronary angiography and peaked at 48, 24 and 6
      hours, respectively. SCr, CysC and NGAL were significantly lower in the
      alprostadil plus statins group than in the statins group (P < 0.05). The
      incidence of CIN in the alprostadil plus statins group was slightly lower than in
      the statins group. The incidence of adverse events within six months in the
      alprostadil plus statins group was significantly lower than in the statins group
      (P = 0.034). CONCLUSIONS: Intravenous alprostadil in combination with oral
      statins is superior to statins alone for protecting renal function in patients
      with mild to moderate renal dysfunction who undergo coronary angiography, and can
      reduce the incidence of adverse events seen within six months.

PMID- 24034094
TI  - Gender disparity in early death after ST-elevation myocardial infarction.
AB  - BACKGROUND: Females with acute myocardial infarction (AMI) have a higher risk of
      adverse outcomes because of receiving less evidence-based medical care. Our aim
      was to investigate the gender disparity in early death after ST-elevation
      myocardial infarction (STEMI) in the current era. METHODS: A total of 1429
      consecutive patients with STEMI in the Liaoning district were analyzed. We
      compared hospital care and cardiac event data by sex for in-patients with acute
      STEMI within 24 hours of symptom onset. RESULTS: In the emergency reperfusion
      group (n = 754), in-hospital mortality occurred in 4.2% of the males and 11.2% of
      the females (P = 0.001). In the non-emergency reperfusion group (n = 675), in
      hospital mortality occurred in 13.0% of the males and 22.9% of the females (P =
      0.001). Multivariate Logistic regression analysis revealed female sex as an
      independent risk factor of death for STEMI patients during hospitalization (OR =
      1.691, P = 0.007). After controlling for patients who died within 24 hr after
      admission, female sex was no longer an independent risk factor (OR = 1.409, P =
      0.259). CONCLUSION: Female sex was an independent risk factor for in-hospital
      mortality of STEMI patients, which is explained by an excess of very early
      deaths.

PMID- 24034095
TI  - Predicted lower limit of normal reduces misclassification risk of airflow
      limitation in asymptomatic elderly never-smokers.
AB  - BACKGROUND: It remains controversial what better defines abnormal lung function
      at the extremes of age. This study aimed to establish new spirometric reference
      equations for residents in Jinan and compare the most accepted two spirometric
      definitions of chronic obstructive pulmonary disease (COPD)-a fixed post
      bronchodilator ratio of forced expiratory volume in one second to forced vital
      capacity (FEV1/FVC) below 70% vs. FEV1/FVC < lower limit of normal (LLN)-in an
      elderly population (age >=60 years). METHODS: Among 10 002 cases, only never
      smokers who had no respiratory symptoms or diagnoses of cardiopulmonary diseases
      and whose lung function measurements strictly followed the American Thoracic
      Society guidelines, were included in the statistical analysis. For each gender,
      prediction equations of FEV1, FVC, FEV1/FVC and corresponding LLN values were
      developed using multiple regression models. RESULTS: In this cross-sectional
      study, spirometric reference values were statistically derived from a sample of
      1328 healthy never-smokers (672 males, 656 females), age 56-84 years. As
      expected, age and height were the main predictors for all lung function
      parameters. Using the two spirometric definitions, the number of pulmonary
      function test results interpreted as obstructed varied markedly in the elderly
      population for both genders (males: chi(2) = 19.59, P < 0.01; females: chi(2) =
      5.67, P = 0.017). CONCLUSIONS: The Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) criterion probably leads to overdiagnosis in asymptomatic elderly
      never-smokers. Our study suggests that the predicted LLN values will reduce the
      misclassification risk instead. However, cohort studies are urgently needed for
      clinical validation.

PMID- 24034096
TI  - Benefits of intra-operative systemic chemotherapy during curative surgery in
      patients with locally advanced gastric cancer.
AB  - BACKGROUND: There is little information on the impact of intra-operative systemic
      chemotherapy on gastric cancer. The aim of this study was to identify prognostic
      factors in patients with locally advanced gastric cancer and undergoing curative
      resection, with a focus on evaluating survival benefits and tolerance of intra
      operative systemic chemotherapy. METHODS: We retrospectively analyzed
      clinicopathological data for 264 consecutive patients who underwent curative
      resection for gastric cancer at Peking Union Medical College Hospital from
      January 2002 to January 2007. Survival curves were plotted using the Kaplan-Meier
      method and compared using log-rank tests. Univariate and multivariate analyses
      were performed with the Cox proportional hazard model. RESULTS: Patients who
      received intra-operative systemic chemotherapy had higher 5-year overall survival
      and 5-year disease-free survival rates (P = 0.019 and 0.010, respectively) than
      patients who did not receive intra-operative systemic chemotherapy. In the
      subgroup analysis, systemic intra-operative chemotherapy benefited the 5-year
      overall survival and disease-free survival rates for patients with cancer of
      stage pTNM IB-IIIB, but not stage pTNM IIIC. Patients who received intra
      operative systemic chemotherapy in combination with post-operative chemotherapy
      had higher 5-year overall survival and 5-year disease-free survival rates (P =
      0.046 and 0.021, respectively) than patients who only received postoperative
      chemotherapy. However, the difference in these rates between patients who
      received only intra-operative systemic chemotherapy and patients who only
      received curative surgery was not statistically significant (P = 0.150 and 0.170,
      respectively). Multivariate analyses showed that intra-operative systemic
      chemotherapy was a favorable prognostic factor for the overall survival and
      disease-free survival rates (P = 0.048 and 0.023, respectively). No grade 4
      toxicities related to intra-operative systemic chemotherapy were recorded within
      the 4 weeks after surgery. CONCLUSION: Intra-operative systemic chemotherapy
      during curative surgery may benefit patients with stage pTNM IBIIIB gastric
      cancer in terms of both overall survival and disease-free survival.

PMID- 24034097
TI  - Psychological symptoms and associated risk factors in Chinese freshmen: a three
      year follow-up study.
AB  - BACKGROUND: The first year of attending university induces a stressful experience
      for many college students. The experience exposes these students to challenging
      circumstances and raises expectations, which consequently increases the risk of
      psychiatric disorders and may exacerbate pre-existing problems. This study was
      designed to explore the risk factors of psychological symptoms among freshmen in
      China. METHODS: A three-year follow-up study was designed in a sample of Chinese
      college freshmen. To set up the baseline interviews, subjects from 25 high
      schools in Beijing were interviewed during the first year in high school. Three
      years later, we followed up with the 1547 students from 15 of the previously
      selected 25 high schools after they had entered universities. Association between
      potential risk factors and the occurrence of psychological symptoms measured by
      the Symptoms Check List-90 was evaluated in unconditional logistic regression
      models with Wald test. RESULTS: Among the 1547 interviewed college freshmen in
      the study, 120 students (7.8%) manifested at least one psychological symptom.
      Personality dysfunction (OR = 3.655, 95% CI 1.967-6.793), parental rejection (OR
      = 2.619, 95% CI 1.544-4.442), age >= 20 (OR = 2.578, 95% CI 1.227-5.418),
      disfavored university (OR = 2.054, 95% CI 1.376-3.066), non-first-choice academic
      major (OR = 1.887, 95% CI 1.255-2.837) and no orientation (OR = 1.739, 95% CI
      1.025-2.951) were determined to be the risk factors of psychological symptoms
      among the college freshmen in China. CONCLUSIONS: Psychological symptoms of
      college freshmen are associated with personality traits, parental rearing
      behavior and study environment. Therefore, it is important to pay attention to
      changes in mental health as students enter or decide on colleges and increase
      education geared towards mental health issues for students in high school and
      universities in China.

PMID- 24034098
TI  - Pattern of instent neointimal formation compared to native atherosclerosis in the
      coronary bifurcation lesions: volumetric intravascular ultrasound analysis.
AB  - BACKGROUND: No clinical study has systematically analyzed and compared
      circumferential neointimal and plaque distribution of stent neointimal
      proliferation and in native atherosclerotic plaques. This study aimed to
      investigate and compare the pattern of instent neointimal formation and native
      atherosclerosis in the coronary bifurcation lesions by volumetric analysis using
      systematic intravascular ultrasound (IVUS). METHODS: We examined bifurcation
      lesions in native coronary artery (plaque group, n = 102) and stented
      bifurcations at 9-month follow-up (neointima group, n = 51) using volumetric IVUS
      analysis of both the main vessel (MV) and side branch (SB). Three 5-mm segments
      were analyzed; the proximal MV (MVp), distal MV (MVd) and SB ostium (SBo). For
      each segment, volumetric analysis was performed in each of four quadrants
      (divided according to the branch takeoff and the geometric center of the lumen);
      carinal, epicardial, abcarinal, and myocardial. The eccentricity index was
      defined as the ratio of the abcarinal plaque (or neointimal) volume to the
      carinal plaque (or neointimal) volume. RESULTS: The plaque distribution differed
      significantly between the four quadrants, with the largest in the abcarinal
      quadrant, followed by the myocardial, epicardial, and carinal quadrants. The
      distribution of neointima was similar in the MV, but the four quadrants in the SB
      did not differ significantly. The eccentricity indices of both the MVd (P <
      0.001) and SBo (P = 0.001) were significantly higher for the plaque group than
      the neointima group. CONCLUSIONS: The distribution of neointimal proliferation
      seems to have a similar pattern to that of atherosclerotic plaque in native
      coronary arteries, particularly in the main vessel, but the trend is less
      prominent.

PMID- 24034099
TI  - Reoperation on aortic disease in patients with previous aortic valve surgery.
AB  - BACKGROUND: Aortic valve replacement (AVR) is a safe and effective method in the
      treatment of aortic valve diseases. This study aimed to increase the
      understanding on re-treatment of aortic diseases after aortic valve surgery
      through a retrospective analysis of 47 related cases. METHODS: Forty-seven
      patients (38 males and 9 females) with previous aortic valve surgery have
      received reoperation on aorta from January 2003 to June 2012, and the mean
      interval time of re-intervention to aortic disease was 6 years ((6.0 +/- 3.8)
      years). The secondary aortic surgery included aortic root replacement (14 cases),
      ascending aorta replacement (10 cases), aortic root/ascending aorta plus total
      arch replacement with stented elephant trunk implantation (21 cases), and total
      thoracoabdominal aorta replacement (2 cases). All these patients have received
      outpatient re-exams or follow-up by phone calls. RESULTS: After the initial
      aortic valve replacement, patients suffered from aortic dissection (25 cases,
      53%), ascending aortic aneurysm (12 cases, 26%) or aortic root aneurysm (10
      cases, 21%). Diameter in ascending aorta increased (5.2 +/- 7.1) mm per year and
      aortic sinus (3.3 +/- 3.1) mm per year. The annual growth value of diameter in
      ascending aorta was higher in patients with rheumatic heart disease than that in
      Marfan syndrome (P < 0.05). All 47 patients have received reoperation on aorta.
      One patient died in operating room because aortic dissection seriously involved
      right coronary artery. Seven patients had renal insufficiency after operation;
      neurological complications occurred in 14 patients including 7 patients with
      stroke and the others with transient brain dysfunction. All patients were
      followed up, the mean survival time was (97.25 +/- 17.63) months, 95% confidence
      interval was 55.24-73.33 months. Eight cases were died during follow-up and five
      year survival rate was 83%. CONCLUSION: To reduce the aortic adverse events after
      first aortic valve surgery, it is necessary to actively treat and strictly follow
      up patients with previous aortic operation especially patients with Marfan
      syndrome and rheumatic heart disease.

PMID- 24034100
TI  - Effect of endoscopic retrograde cholangiopancreatography combined with
      laparoscopy and choledochoscopy on the treatment of Mirizzi syndrome.
AB  - BACKGROUND: Mirizzi syndrome is often difficult to diagnose before surgery, and
      is often accompanied by extensive adhesions in the cystohepatic (Calot's)
      triangle and the difficulty of separating tissue can lead to bile duct injury and
      other intraoperative and postoperative complications. The aim of this study is to
      investigate minimally invasive means of treating different types of Mirizzi
      syndrome. METHODS: Fifty-four patients diagnosed with Mirizzi syndrome were
      enrolled between July 2004 and May 2012. The diagnosis was further refined
      according to the Csendes classification. Twenty-seven patients were treated with
      a combination of endoscopic retrograde cholangiopancreatography (ERCP),
      laparoscopy, and choledochoscopy (tripartite approach group); type I in 16 cases,
      type II five cases, and type III in six cases. Twenty-seven patients were treated
      with laparotomy (routine approach group); type I in 19 cases, type II in six
      cases, and type III in two cases. The operation time, blood loss during
      operation, initiation of intake time of food, postoperative complications, and
      hospital stays were compared between two groups. RESULTS: All patients were
      successfully cured in surgical operation. The operation time was (49.7 +/- 27.5)
      minutes, blood loss during operation was (21.1 +/- 15.9) ml, initiation of intake
      time of food was (6.3 +/- 2.7) hours, postoperative complications were with two
      cases (7%, 2/27), and hospital stay was (6.7 +/- 1.8) days in the tripartite
      approach group. In the routine approach group, the operation time was (85.1 +/-
      20.3) minutes, blood loss during operation was (150.3 +/- 20.5) ml, initiation of
      intake time of food was (36.6 +/- 10.3) hours, postoperative complications were
      with three cases (11%, 3/27), and hospital stay was (10.9 +/- 3.4) days. Except
      for postoperative complications, there were significant differences in the
      operation time, blood loss during operation, initiation of intake time of food,
      and hospital stays between two groups (P < 0.05). CONCLUSIONS: ERCP combined with
      laparoscopy and choledochoscopy is a safe and effective means of treating Mirizzi
      syndrome. The approach is minimally invasive and patients recover quickly
      requiring only brief hospitalization.

PMID- 24034101
TI  - Stenting of iliac vein obstruction following catheter-directed thrombolysis in
      lower extremity deep vein thrombosis.
AB  - BACKGROUND: Catheter-directed thrombolysis (CDT) for deep venous thrombosis (DVT)
      of the lower extremity has good effect, but whether iliac vein stent placement
      after thrombolytic therapy is still controversial. The goal of this study was to
      evaluate the efficacy of stent placement in the iliac vein following CDT in lower
      extremity DVT. METHODS: This was a single-center, prospective, randomized
      controlled clinical trial. After receiving CDT, the major branch of the distal
      iliac vein was completely patent in 155 patients with lower extremity DVT, and 74
      of these patients with iliac vein residual stenosis of >50% were randomly divided
      into a control group (n = 29) and a test group (n = 45). In the test group,
      stents were implanted in the iliac vein, whereas no stents were implanted in the
      control group. We evaluated the clinical indicators, including patency of the
      deep vein, C in CEAP classification, Venous Clinical Severity Score (VCSS), and
      Chronic Venous Insufficiency Questionnaire (CIVIQ) Score. RESULTS: All patients
      had postoperative follow-up visits for a period of 6-24 months. Venography or
      color ultrasound was conducted in subjects. There was a significant difference
      between the patency rate at the last follow-up visit (87.5% vs. 29.6%) and the 1
      year patency rate (86.0% vs. 54.8%) between the test and control groups. The
      change in the C in CEAP classification pre- and post-procedure was significantly
      different between the test and control groups (1.61 +/- 0.21 vs. 0.69 +/- 0.23).
      In addition, at the last follow-up visit, VCSS and CIVIQ Score were both
      significantly different between the test and control groups (7.57 +/- 0.27 vs.
      0.69 +/- 0.23; 22.67 +/- 3.01 vs. 39.34 +/- 6.66, respectively). CONCLUSION: The
      stenting of iliac vein obstruction following CDT in lower extremity DVT may
      increase the patency of the deep vein, and thus provides better efficacy and
      quality of life.

PMID- 24034102
TI  - Clinical classification and treatment of leukokeratosis of the vocal cords.
AB  - BACKGROUND: Leukokeratosis of the vocal cords is a clinical descriptive
      diagnosis, which includes a group of squamous intraepithelial lesions of the
      vocal cord mucosa. We investigated the clinical classification and treatment
      efficacy of leukokeratosis of the vocal cords. METHODS: We conducted a
      retrospective analysis of the medical history, laryngoscopic examinations,
      morphological features under a surgical microscope, and pathology results of 360
      cases of leukokeratosis of the vocal cords to examine correlations among
      treatment modalities, therapeutic effects, and clinical features. RESULTS: All
      cases were divided into four types based on symptoms, examination results, and
      treatment efficacies as follows: 21 patients had type I inflammatory leukoplakia
      and their vocal cord morphology and voice quality recovered after conservative
      therapies; 76 patients had type II frictional polyps and received CO2 laser
      submucosal cordectomy; 68 patients had type III sulcus vocalis and received
      mucosal slicing with dredging; and 195 cases had type IV simple leukokeratosis
      and received partial subligamental cordectomy with CO2 lasers or transmuscular
      cordectomy. Our treatment achieved a surgical cure rate of 90.9% (308/339), with
      a recurrence rate of 9.1% (31/339) and malignant transformation rate of 6.5%
      (22/339). All cancerous transformations occurred in type IV patients. CONCLUSION:
      Choosing conservative or CO2 laser surgery based on the morphological
      characteristics of squamous epithelial lesions of keratinized vocal cord mucosa
      can maximally protect voice quality, reduce complications, and improve the cure
      rate.

PMID- 24034103
TI  - Electrophysiological characteristics of cardiomyocyte-like cells from rat bone
      marrow derived mesenchymal stem cells by four inductors.
AB  - BACKGROUND: Bone marrow derived mesenchymal stem cells (BMdMSCs) can
      differentiate into cardiomyocyte-like cells induced by different inductors
      individually or collectively. In this study, by inducing BMdMSCs with p53
      inhibitor (p-fifty three inhibitor-alpha, PFT-alpha), 5-azacytidine (5-AZA),
      angiotensin-II (Ang-II) and bone morphogenic protein-2 (BMP-2) we compared the
      influences of four inductors on the differentiation of rat BMdMSCs into
      caridomyocyte like-cells. METHODS: BMdMSCs were collected from the bone marrow of
      Sprague Dawley rats and after the fourth generation, the purified cells were
      divided into five groups: 5-AZA (10 umol/L), Ang-II (0.1 umol/L), PFT-alpha (20
      umol/L), BMP-2 (10 ug/L) and control. The purity of the BMdMSCs and the cardiac
      differentiation rates were obtained by flow cytometry. The expressions of cTnT in
      the BMdMSCs after four weeks of induction were detected by immunofluorescence and
      the expressions of cTnI and Cx43 detected by Western blotting. The green
      fluorescent levels reflecting intracellular calcium transient function were
      determined by laser scanning confocal microscopy. The total potassium current
      levels of cells were measured on patch clamp. RESULTS: All inductors affected to
      a different degree the differentiation of BMdMSCs into cardiomyocyte-like cells
      and the expressions of cTnT, cTnI and Cx43 suggesting that the combination of
      inductors could be an improved method for cardiac regenerative medicine. In
      addition, the total potassium current level and calcium transient in PFT-alpha
      cardiomyocyte-like cells were higher than other groups. CONCLUSIONS: The cardiac
      differentiation of BMdMSCs induced by PFT-alpha, 5-AZA, Ang-II and BMP-2 has been
      improved at different levels. PFT-alpha has an advantage of differentiation rate
      and electrophysiological function over other inductors.

PMID- 24034104
TI  - A modified tricuspid valve annuloplasty technique for functional tricuspid
      regurgitation.
AB  - BACKGROUND: Functional tricuspid regurgitation often occurs in patients with
      concomitant left sided, valve disease. Several types of tricuspid valve
      annuloplasty have been described, but there is no consensus on the management of
      functional tricuspid regurgitation. We report a modified annuloplasty technique
      and compare its efficacy with the conventional Kay technique. METHODS: A
      retrospective review was made of 60 patients who received tricuspid valve
      annuloplasty (group A, modified method; group B, Kay technique) and the early and
      midterm outcomes of modified method and Kay technique were compared. RESULTS:
      Three patients underwent ring annuloplasty using a semirigid Carpentier-Edwards
      ring due to failing suture annuloplasty. All patients were completely cured when
      they left the hospital. The follow-up time was (32 +/- 7) months in group A and
      (30 +/- 7) months in group B. After three years, tricuspid regurgitation
      decreased by more than two grades in 13 patients in group A and 11 in group B.
      The mean postoperative regurgitation grade in group A was lower than group B at
      12, 24 and 36 months but not significantly. Three of 28 patients developed
      recurrent tricuspid regurgitation in group A and five of 26 patients in group B
      during the follow-up period (three deaths and three ring annuloplasties
      excluded). Freedom from recurrent tricuspid regurgitation in group A was higher
      than that group B at all follow-up points. Postoperative right atrium diameter,
      right ventricle endodiastolic dimension and tricuspid regurgitation area
      decreased obviously in both groups. The right ventricle endodiastolic dimension
      and tricuspid regurgitation area improved more significantly in group A than
      group B over three years of follow-up, CONCLUSIONS: The modified annuloplasty
      technique achieved the same outcomes as the conventional Kay annuloplasty over
      the first three years postoperation. As this modified technique is simple and
      less expensive, it is another option for correction of functional tricuspid
      regurgitation.

PMID- 24034105
TI  - Inhibition of p38 activity reverses claudin-6 induced cell apoptosis, invasion,
      and migration.
AB  - BACKGROUND: Claudin-6 is a protein component of tight junctions and its
      expression could downregulate the malignant phenotype of breast carcinoma. Here
      we investigated the mechanisms of claudin-6 induced human MCF-7 breast cancer
      cells apoptosis, invasion, and migration. METHODS: Terminal deoxyribonucleotide
      transferase-mediated nick-end labeling assay and Annexin-V/PI double stain assay
      were carried out to evaluate apoptosis. Inhibitors of each pathway were used to
      inactivate the signaling pathways. The expression of claudin-6 and phosphate p38,
      Erk 1/2 and Akt protein levels was confirmed by Western blotting analysis.
      Invasive and migratory traits of claudin-6 expressing cells were determined by
      Boyden chamber invasion assay and monolayer wound-healing assay. RESULTS: Cells
      with high-level expression of claudin-6 had a higher rate of apoptosis than
      control cells. Western blotting assay showed that by contrast to control groups,
      p38 pathways were more activated in claudin-6 expressing cells. However, after
      inhibitor SB203580 treatment, the activation status could be significantly
      counteracted. Furthermore, by applying inhibitors to the apoptotic rate, invasive
      and migratory traits were also recovered in cells with claudin-6 expression.
      CONCLUSION: Claudin-6 may function through p38 mitogen-activated protein kinase
      pathway, of which inhibition may reverse claudin-6-induced cell apoptosis,
      invasion, and migration.

PMID- 24034106
TI  - Future application of hair follicle stem cells: capable in differentiation into
      sweat gland cells.
AB  - BACKGROUND: Sweat glands (SGs) can not regenerate after complete destruction in
      the severe skin injury, so it is important to find a ideal stem cell source in
      order to regenerate functional SGs. Hair follicle stem cells (HFSCs) possess the
      obvious properties of the adult stem cells, which are multipotent and easily
      accessible. In this research, we attempted to direct the HFSCs suffered from the
      sweat gland cells (SGCs) special differentiation by a co-operative coculture
      system in vitro. METHODS: The designed co-culture microenvironment in the
      transwell was consist of two critial factors: heat shocked SGCs and dermis-like
      mesenchymal tissue, which appeared independently in the two control groups; after
      induction, the purified induced SGC-like cells were transplanted into the full
      thickness scalded wounds of the nude mice, after 4 weeks, the reconstructed SG
      like structures were identified by immunohistochemical and immunofluorescence
      analysis. RESULTS: A part of HFSCs in experimental group finally expressed SGCs
      phenotypes, by contrast, the control group 1 which just containing dermis-like
      mesenchymal tissue failed and the control group 2 consisted of heat shocked SGCs
      was in a poor efficiency; by immunofluorescence staining and flow cytometry
      analysis, the expression of HFSCs special biomarkers was down regulated, instead
      of the positive efficiency of SGCs special antigens increased; besides, the
      induced SGCs displayed a high expression of ectodysplasin A (EDA) and
      ectodysplasin A receptor (EDAR) genes and proteins; after cell transplantation,
      the youngest SG-like structures formed and be positive in SGCs special antigens,
      which never happened in untreated wounds (P < 0.05). CONCLUSION: The HFSCs are
      multipotential and capable in differentiating into SGCs which promise a potential
      stem cells reservoir for future use; our special co-culture microenvironment is
      promising for HFSCs differentiating; the induced SGCs are functional and could
      work well in the regeneration of SGs.

PMID- 24034107
TI  - Effects of low molecular weight heparin on clot rate and activated clotting time:
      an in vitro study.
AB  - BACKGROUND: Due to lack of point-of-care testing, the use of low-molecular-weight
      heparin (LMWH) therapy in some special patients is restricted. This study was
      designed to explore the effects of LMWH on clot rate (CR) and activated clotting
      time (ACT), and to search for an appropriate method for bedside monitoring of
      anticoagulant activity of LMWH. METHODS: Thirty-two healthy volunteers were
      selected from the staff of Beijing Tongren Hospital. CR and ACT were measured
      with different reagents (glass beads, diatomite, kaolin and magnetic bar) on
      blood samples spiked with increasing concentrations of LMWH (dalteparin, 0.2-1.8
      IU/ml). Correlations between concentrations of LMWH and values of CR and ACT were
      analysed based on the data obtained and regression analysis was performed to
      establish a regression equation. RESULTS: With the increase in doses of
      dalteparin, CR values reduced gradually. The values of CR of four reagents (glass
      beads, diatomite, kaolin and magnetic bar) were 20.4-4.5 IU/min, 27.4-6.9 IU/min,
      27.5-7.9 IU/min and 7.8-0.1 IU/min respectively and an linear relationship was
      observed between the CR values and dalteparin concentrations (P < 0.05). The
      values of ACT were 173-615 seconds, 130-270 seconds, 123-226 seconds, 337-1411
      seconds respectively, which showed a linear regression between the ACT values and
      dalteparin concentrations (P < 0.01). Differences in slope of the regression
      curves of ACT were observed with all the reagents tested (glass beads 248.2 s/IU,
      diatomite 74.8 s/IU, kaolin 58.2 s/IU and magnetic bar 1112.2 s/IU, P < 0.01).
      While the minimum concentration of dalteparin was 0.2 IU/ml, 0.4 IU/ml, 1.4 IU/ml
      and 0.2 IU/ml separately, the ACT values of the four coagulants (glass beads,
      diatomite, kaolin and magnetic bar) were beyond the normal limit and showed a
      noticeable increase respectively (P < 0.01). CONCLUSIONS: This study showed that
      there was an excellent linear relationship between the CR and ACT values and
      dalteparin concentrations for all the four reagents (glass beads, diatomite,
      kaolin and magnetic bar) in vitro. The sensitivity of different coagulation
      reagents to LMWH different. Choosing a suitable reagent, both CR and ACT were
      possible to be used as a convenient bedside test for LMWH.

PMID- 24034108
TI  - Zinc ion implantation-deposition modification of titanium for enhanced adhesion
      of focal plaques of osteoblast-like cells.
AB  - BACKGROUND: Surface modification by ion implantation-deposition is well
      established in materials science and can be an effective way to improve
      biocompatibility. The aim of this study is to evaluate the chemical composition
      of a modified titanium (Ti) surface after zinc (Zn) ion implantation and
      deposition and examine the effect of the modification on the formation of
      cellular focal adhesion plaques in vitro. METHODS: cp-Ti discs were modified with
      Zn ion implantation and deposition via PIIID. The chemical composition of the
      surface modification was characterized by X-ray photoelectron spectroscopy (XPS).
      The formation of focal adhesion plaques on the modified Ti was investigated with
      human osteoblast-like MG-63 cells that were seeded onto the Ti surfaces and
      quantified by morphometric analysis under a confocal microscope. RESULTS: XPS
      data revealed that the modified Zn-Ti surface consisted of Ti, oxygen, Zn, and
      carbon. In addition, Gaussian fitting of the spectra indicated that the modified
      surface contained titanium dioxide and zinc oxide. After 6 hours of MG-63 cell
      culture, there were significantly more focal adhesion plaques on the modified
      surfaces than observed on the nonmodified Ti (P < 0.05). CONCLUSION: Zn ion
      implantation and deposition greatly improved the biocompatibility of Ti for the
      growth of MG-63 cells.

PMID- 24034109
TI  - A new gene ontology-based measure for the functional similarity of gene products.
AB  - BACKGROUND: Although biomedical ontologies have standardized the representation
      of gene products across species and databases, a method for determining the
      functional similarities of gene products has not yet been developed. METHODS: We
      proposed a new semantic similarity measure based on Gene Ontology that considers
      the semantic influences from all of the ancestor terms in a graph. Our measure
      was compared with Resnik's measure in two applications, which were based on the
      association of the measure used with the gene co-expression and the protein
      protein interactions. RESULTS: The results showed a considerable association
      between the semantic similarity and the expression correlation and between the
      semantic similarity and the protein-protein interactions, and our measure
      performed the best overall. CONCLUSION: These results revealed the potential
      value of our newly proposed semantic similarity measure in studying the
      functional relevance of gene products.

PMID- 24034110
TI  - Advances on hypoxia inducible factor-1.

PMID- 24034111
TI  - Fatal hemolysis due to clostridium perfrigens blood stream infection.

PMID- 24034112
TI  - Is trapping a safe method to treat complex internal carotid aneurysms?

PMID- 24034113
TI  - Expression of human WFDC2 protein from patients with serous carcinomas by the two
      tier system.

PMID- 24034114
TI  - Rosuvastatin escape in a Chinese elderly with hyperlipidemia.

PMID- 24034115
TI  - Optic neuritis combined with hepatitis B and neurosyphilis.

PMID- 24034116
TI  - Steel wire causing pseudoaneurysm of descending aorta.

PMID- 24034117
TI  - Primary Hodgkin disease of the spine could mimic eosinophilic granuloma
      initially.

PMID- 24034118
TI  - Hemophagocytic syndrome: a rare but fatal complication after liver
      transplantation.

PMID- 24034119
TI  - Subcutaneous panniculitis-like T-cell lymphoma accompanied with discoid lupus
      erythematosus.

PMID- 24034120
TI  - Progressive macular hypomelanosis with asymmetrically distributed lesions.

PMID- 24034121
TI  - Cervical granulocytic sarcoma.

PMID- 24034122
TI  - A fast growing conjunctival malignant melanoma.

PMID- 24034123
TI  - Hepatic resection for intrahepatic cholangiocarcinoma after a failed trial of
      radiofrequency ablation.

PMID- 24034124
TI  - Neuroblastoma mistaken for acute leukemia based on bone marrow morphology.

PMID- 24034125
TI  - Acute leukemic iridocylitis in an adult with acute lymphoblastic leukemia as an
      initial presentation of relapse.

PMID- 24034126
TI  - Ataxia and arbovirus.

PMID- 24034127
TI  - A "tricky" subarachnoid hemorrhage.

PMID- 24034128
TI  - A case of limbic encephalitis with positive antibody to the GABAB receptor.

PMID- 24034129
TI  - Caenorhabditis elegans-based in vivo screening of bioactives from marine sponge
      associated bacteria against Vibrio alginolyticus.
AB  - AIM: To establish Caenorhabditis elegans based in vivo method for screening
      bioactives from marine sponge associated bacteria (SAB) against Vibrio species.
      METHODS AND RESULTS: About 256 SAB isolates were screened for their ability to
      rescue C. elegans infected with Vibrio species. The chloroform extract of the
      positive isolate was subjected to column fractionation and purity of the active
      fraction was analysed using HPLC. Further, the components were elucidated using
      GC/MS. The active fraction was tested for its in vivo rescue activity,
      antibacterial and anti-QS activity. In vivo colonization reduction and biofilm
      inhibition efficiency were assessed using GFP-tagged V. alginolyticus using
      confocal laser scanning microscopy (CLSM). The ability of the active fraction in
      modulating expression of V. alginolyticus quorum sensing (QS) regulators luxT and
      lafK was measured using real-time PCR. The results indicated that the chloroform
      extract of SAB4.2 displayed significant rescue activity against V. alginolyticus
      by inhibiting the QS pathway. HPLC analysis of the active fraction revealed a
      single major peak and GC/MS analysis suggested Pyrrolo[1,2-a]pyrazine-1,4-dione,
      hexahydro-3-(2-methylpropyl) as the major constituent. The potent bacterial
      isolate was identified as Alcaligenes faecalis. CONCLUSIONS: In vivo screening
      using C. elegans identified a marine isolate that inhibits the virulence of V.
      alginolyticus by interrupting the QS pathway. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The study provides a C. elegans based in vivo screening method for
      identifying bioactives from natural resources by overcoming the disadvantages of
      traditional in vitro plate assays.

PMID- 24034130
TI  - Ibopamine challenge test can be used to differentiate glaucoma suspects from
      glaucoma patients.
AB  - BACKGROUND: Many countries face the challenge of a rising number of patients with
      or at risk of developing glaucoma. A test to differentiate between people who are
      unlikely to develop glaucoma and those at risk for the disease could be
      clinically useful. Ibopamine, when administered topically, temporarily increases
      aqueous production. Normal eyes with healthy trabecular meshwork show no
      significant change in intraocular pressure (IOP) following an ibopamine
      challenge; however, those with glaucoma demonstrate elevated IOP. DESIGN: The
      study was designed as a prospective case-control study in a tertiary hospital.
      PARTICIPANTS: Patients were recruited consecutively as they presented to glaucoma
      clinics at Flinders Medical Centre (n = 39); the sample included 18 glaucoma
      suspects and 21 patients with glaucoma. All patients had open anterior chamber
      angles and no evidence of secondary glaucoma. METHODS: Patients underwent IOP
      measurements followed by instillation of ibopamine 2% solution and subsequent
      repeated IOP assessment. The difference between the baseline measurement and that
      taken at 45 min was determined and compared between groups. MAIN OUTCOME MEASURE:
      The outcome measure was the positivity of the ibopamine challenge test, defined
      by an increase in IOP > 3 mmHg. RESULTS: We observed a mean increase in IOP of
      1.9 +/- 1.6 mmHg or 12.5 +/- 10.3%) for glaucoma suspects and 7.4 +/- 4 mmHg or
      52.4 +/- 26.5% for glaucoma patients (P < 0.0001). Four glaucoma suspects (22%)
      and 19 glaucoma patients (90%) tested positive (P < 0.0001). CONCLUSION: This
      study demonstrates that ibopamine has potential as a test to differentiate
      glaucoma suspects from patients with glaucoma.

PMID- 24034131
TI  - Ethnobotanical appraisal and cultural values of medicinally important wild edible
      vegetables of Lesser Himalayas-Pakistan.
AB  - BACKGROUND: The association among food and health is momentous as consumers now
      demand healthy, tasty and natural functional foods. Knowledge of such food is
      mainly transmitted through the contribution of individuals of households.
      Throughout the world the traditions of using wild edible plants as food and
      medicine are at risk of disappearing, hence present appraisal was conducted to
      explore ethnomedicinal and cultural importance of wild edible vegetables used by
      the populace of Lesser Himalayas-Pakistan. METHODS: Data was collected through
      informed consent semi-structured interviews, questionnaires, market survey and
      focus group conversation with key respondents of the study sites including 45
      female, 30 children and 25 males. Cultural significance of each species was
      calculated based on use report. RESULTS: A total of 45 wild edible vegetables
      belonging to 38 genera and 24 families were used for the treatment of various
      diseases and consumed. Asteraceae and Papilionoideae were found dominating
      families with (6 spp. each), followed by Amaranthaceae and Polygonaceae.
      Vegetables were cooked in water (51%) followed by diluted milk (42%) and both in
      water and diluted milk (7%). Leaves were among highly utilized plant parts (70%)
      in medicines followed by seeds (10%), roots (6%), latex (4%), bark, bulb,
      flowers, tubers and rhizomes (2% each). Modes of preparation fall into seven
      categories like paste (29%), decoction (24%), powder (14%), eaten fresh (12%),
      extract (10%), cooked vegetable (8%) and juice (4%). Ficus carica was found most
      cited species with in top ten vegetables followed by Ficus palmata, Bauhinia
      variegata, Solanum nigrum, Amaranthus viridis, Medicago polymorpha, Chenopodium
      album, Cichorium intybus, Amaranthus hybridus and Vicia faba. CONCLUSIONS:
      Patterns of wild edible plant usage depend mainly on socio-economic factors
      compare to climatic conditions or wealth of flora but during past few decades
      have harshly eroded due to change in the life style of the inhabitants. Use
      reports verified common cultural heritage and cultural worth of quoted taxa is
      analogous. Phytochemical analysis, antioxidant activities, pharmacological
      applications; skill training in farming and biotechnological techniques to
      improve the yield are important feature prospective regarding of wild edible
      vegetables.

PMID- 24034132
TI  - Management of preanalytical phase for routine hematological testing: is the
      pneumatic tube system a source of laboratory variability or an important facility
      tool?

PMID- 24034133
TI  - Impact of cilostazol on the progression of carotid atherosclerosis in patients
      with retinal vascular occlusion.
AB  - BACKGROUND: Cilostazol, a selective phosphodiesterase three inhibitor, has been
      proposed to have beneficial effects in the prevention of atherosclerosis. AIMS:
      We aimed to investigate the effects of cilostazol on carotid intima-media
      thickening (IMT) and total plaque area (TPA) in patients with retinal vascular
      occlusion. METHODS: A total of 63 consecutive vascular occlusive retinopathy
      patients with carotid atherosclerosis were enrolled. We examined changes in the
      carotid IMT/TPA and visual acuity/macular thickness before and after 1-year
      treatment with cilostazol (200 mg/day). RESULTS: The mean IMT of both common
      carotid arteries (CCAs) and internal carotid arteries (ICAs) were significantly
      reduced after cilostazol treatment. There was no significant difference in the
      TPA of both CCAs before and after the treatment (before; 0.61 +/- 0.94 vs. after;
      0.45 +/- 0.79 cm(2) , P = 0.291); however, significant plaque regression (before;
      0.14 +/- 0.15 vs. after; 0.25 +/- 0.14 cm(2) , P = 0.004) was observed in
      selected patients (n = 30) with a TPA <0.5 cm(2) . The improvement in macular
      thickness was significantly associated with an improvement in carotid IMT (r =
      0.42, P = 0.001) and TPA (r = 0.23, P = 0.04). CONCLUSION: Cilostazol potently
      inhibited the progression of carotid IMT and may play a role in the early carotid
      plaque regression in patients with retinal vascular occlusion.

PMID- 24034134
TI  - Structural insights into the arms race between host and virus along RNA silencing
      pathways in Arabidopsis thaliana.
AB  - RNA silencing refers to a conserved sequence-specific gene-regulation mechanism
      mediated by small RNA molecules. In plants, microRNA (miRNA) and small
      interfering RNA (siRNA) represent two major types of small RNA molecules which
      play pivotal roles in plant developmental control and antiviral defences. To
      escape these plant defences, plant viruses have encoded a vast array of viral
      suppressors of RNA silencing (VSRs) to attack the host antiviral silencing
      pathway by interfering with small RNA processing, RNA-induced silencing complex
      (RISC) assembly, viral mRNA cleavage etc. Transgenic plants expressing distinct
      VSRs often show developmental aberrations that resemble the phenotype of miRNA
      deficient mutants, implying a potential intrinsic link between VSRs and the miRNA
      pathway (at least in Arabidopsis thaliana) even though their pathogenic
      mechanisms remain largely unknown. In this review, we summarise our current
      structural understandings of the arms race between the host and virus along the
      RNA silencing pathway in A. thaliana by focusing on several important
      ribonucleoprotein (RNP) structures involved in RNA silencing and unique
      structural features adopted by VSRs.

PMID- 24034135
TI  - Online profiling of triacylglycerols in plant oils by two-dimensional liquid
      chromatography using a single column coupled with atmospheric pressure chemical
      ionization mass spectrometry.
AB  - The complexity of natural triacylglycerols (TAGs) in various edible oils is high
      because of the hundreds of TAG compositions, which makes the profiling of TAGs
      quite difficult. In this investigation, a rapid and high-throughput method for
      online profiling of TAGs in plant oils by two-dimensional (2D) liquid
      chromatography using a single column coupled with atmospheric pressure chemical
      ionization (APCI) mass spectrometry was reported. A novel mixed-mode 2D
      chromatographic column packed with silver-ion-modified octyl and sulfonic co
      bonded silica was employed in this online 2D separation system. This novel 2D
      column combined the features of C8 column and silver-ion. In comparison with the
      traditional C18 column and silver-ion column, which are the two main columns used
      for the separation of complex TAGs in natural oil samples, this novel 2D column,
      could provide hydrophobic interactions as well as pi-complexation interactions.
      It exhibited much higher selectivity for the separation of TAGs, and the
      separation was rapid. This online 2D separation system was successful in the
      separation of a large number of TAG solutes, and the TAG structures were
      evaluated by analyzing their APCI mass spectra information. This system was
      applied for the profiling of TAGs in peanut oils, corn oils, and soybean oils. 30
      TAGs in peanut oils, 18 TAGs in corn oils, and 21 TAGs in soybean oils were
      determined and quantified. The highest relative content of TAGs was LLL, which
      was found in corn oil with the relative content up to 45.43 (%, w/w), and the
      lowest relative content of TAGs was LLS and OSS, which was found in soybean oil
      and corn oil respectively, with the relative content only 0.01 (%, w/w). In
      addition, the TAG data were analyzed by principal component analysis (PCA).
      Results of PCA enabled a clear identification of different plant oils. This
      method provided an efficient and convenient chromatographic technology for the
      fast characterization and quantification of complex TAGs in plant oils at high
      selectivity. It has great potential as a routine analytical method for analysis
      of edible oil quality and authenticity control. 

PMID- 24034136
TI  - Purification of omega-3 polyunsaturated fatty acids from fish oil using silver
      thiolate chromatographic material and high performance liquid chromatography.
AB  - Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have become increasingly
      popular in dietary supplements worldwide and global demand for higher purity
      omega-3 PUFAs in clinical applications has been rising rapidly in the recent
      years. Traditional methods for isolating omega-3 PUFAs however, generally require
      multiple, cumbersome steps to obtain high purity (>95%) products. In this study,
      we report an efficient liquid chromatography method for purifying individual
      omega-3 fatty acid ethyl esters (FAEEs), eicosapentaenoic acid (EPA, C20:5) and
      docosahexaenoic acid (DHA, C22:6), at >95% purity using a silver(I)
      mercaptopropyl stationary phase, otherwise known as silver-thiolate
      chromatographic material (AgTCM). We demonstrate the key variables controlling
      separation of FAEEs with a silver(I)-thiolate stationary phase and examine
      important similarities and differences between silver-thiolate and silver-ion
      chromatography in regards to the separation mechanism taking place. We
      demonstrate the separation behavior of FAEEs under various conditions such as
      mobile phase composition, flow rate and sample injection amount. Purification of
      EPA and DHA was carried out on an analytical and semi-preparative scale and the
      resulting purity was determined by GC-FID. We report high attainable purity for
      EPA (>95%) and DHA (>99%) from a single isocratic separation of fish oil FAEEs
      within 5-10min using a mobile phase of heptane/acetone (95:5, % v/v). 

PMID- 24034137
TI  - Systematic comparison of sensitivity between hydrophilic interaction liquid
      chromatography and reversed phase liquid chromatography coupled with mass
      spectrometry.
AB  - Hydrophilic interaction liquid chromatography (HILIC) appears as a promising
      strategy to increase sensitivity with electrospray ionization source (ESI/MS). In
      the present study, peak heights, background noises and signal-to-noise ratios
      (S/N) obtained with HILIC-MS/MS and RPLC-MS/MS conditions were systematically
      compared using a dataset of 56 basic drugs possessing diverse physico-chemical
      properties. Various mobile phase conditions were investigated, including
      different pH (3 and 6 in HILIC; 3, 6 and 9 in RPLC) and flow rates (300, 600 and
      1000MUL/min). The average gain in sensitivity obtained between HILIC and RPLC was
      equal to 7 and 10 at pH 3 and 6, respectively. However, this value was not
      reliable, since it was altered by a few compounds possessing an "extreme"
      behaviour (gain in sensitivity from 100-fold to >8000-fold better). Then, the
      median gain in sensitivity, equal to 4 in our case, whatever the pH, should be
      considered. For about 90% of the tested compounds and analytical conditions, the
      best S/N was systematically attained under HILIC mode. Thanks to PCA
      representation, it was shown that the basic compounds with pKa between 6 and 8
      generally had the best sensitivity in HILIC at pH 6, while the best sensitivity
      for basic analytes possessing pKa higher than 8 was usually obtained in HILIC at
      pH 3. As previously reported, the sensitivity gain in HILIC vs. RPLC was
      explained by the difference in acetonitrile concentration at elution (in average
      29% ACN in RPLC and 82% ACN in HILIC at pH 6) leading to better analytes'
      desolvation. However, it seems that this high proportion of solvent also
      favourably influenced the ionization by modifying pH and pKa. Indeed the weakest
      bases of our training set of compounds (pKa between 2 and 5) showed an
      unexpectedly strong gain in sensitivity, between 20 and 100-fold in comparison to
      RPLC. These results prove that the ionic character of analytes in solution (i.e.,
      pKa and pH) and the ionization mechanism (i.e., proton transfer) also play an
      important role for explaining the sensitivity enhancement in HILIC. 

PMID- 24034138
TI  - Ethyl propiolate derivatisation for the analysis of varietal thiols in wine.
AB  - Varietal thiols [3-mercaptohexan-1-ol (3MH), 3-mercaptohexyl acetate (3MHA) and 4
      mercapto-4-methylpentan-2-one (4MMP)] have been extensively studied in the recent
      literature. Nonetheless the hardest obstacle for research focussing on this class
      of compounds is the lack of quick, user-friendly and sensitive analytical
      methods. The current paper presents the use of ethyl propriolate (ETP) as a novel
      derivatising agent to quantify varietal thiols and the first time quantification
      of the thiol-ETP adducts via gas chromatography-mass spectrometry. Method
      optimisation including choice of the best SPE cartridge, derivatisation pH and
      adducts stability is presented. Validation of the method via stable isotope
      dilution was carried out. Detection limits in both model wine (4MMP 7.2ng/L, 3MHA
      40.0ng/L and 3MH 91.2ng/L) and white wine (4MMP 24.5ng/L, 3MHA 120.9ng/L and 3MH
      194.6ng/L) for the novel ETP-based method were lower than those obtained with the
      p-HMB method. Finally, 14 New Zealand Sauvignon blanc were analysed with both the
      new method and the organo-mercury based procure: good correlations were obtained
      for 3MH and 3MHA. Detection limits obtained with the new methods, its rapidity
      and reproducibility make this protocol perfectly suitable for oenological
      purposes. 

PMID- 24034139
TI  - Anticancer Activity of New Synthetic alpha-Methylene-delta-Lactones on Two Breast
      Cancer Cell Lines.
AB  - Natural products are important leads in drug discovery. The search for effective
      plant-derived anticancer agents or their synthetic analogues has continued to be
      of interest to biologists and chemists for a long time. In this report,
      cytotoxicity and anticancer activity of new synthetic alpha-methylene-delta
      lactones was tested against two breast cancer cell lines, invasive, hormone
      independent MDA-MB-231 and hormone-dependent MCF-7. Cytotoxicity was examined
      using MTT assay. The ability to induce apoptosis and changes in mitochondrial
      membrane potential was studied by flow cytometry. The expression levels of pro-
      and anti-apoptotic genes were determined by quantitative real-time PCR. Cancer
      cell migration and invasion were assessed by wound healing and Matrigel assays.
      Additionally, secretion of proteins associated with invasiveness,
      metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) was
      investigated using commercial ELISA kits and MMP-9 activity by gelatin
      zymography. A natural sesquiterpene lactone, parthenolide, was used as a positive
      control. Screening results showed all four analogues to be highly cytotoxic. The
      most potent compound of the series, 1-isopropyl-2-methylene-1,2
      dihydrobenzochromen-3-one, designated DL-3, which reduced the number of viable
      MDA-MB-231 and MCF-7 cells with the IC50 values of 5.3 MUM and 3.54 MUM,
      respectively, was selected for further research. DL-3 activated the intrinsic
      pathway of apoptosis, associated with the loss of mitochondrial membrane
      potential and changes in Bax/Bcl-2 ratio. DL-3 also inhibited the movement of
      both types of breast cancer cells. Suppression of cell migration and invasion was
      the result of the decreased secretion of enzymes responsible for the degradation
      of the extracellular matrix, MMP-9 and uPA. These findings show that the
      synthetic alpha-methylene-delta-lactone, DL-3, displays potential to be further
      explored in the development of new anticancer agents. 

PMID- 24034140
TI  - Revisions to the international guidelines on the diagnosis and therapy of chronic
      urticaria.
AB  - At the end of 2012, more than 300 participants discussed and agreed on the update
      of the international guidelines on urticaria at the 4th International Consensus
      Meeting (URTICARIA 2012). Currently, the recommendations are in the final process
      of international coordination. In preparation for the update, questions were
      prepared by an expert panel; this was followed by a systematic literature search.
      The questions and the resulting recommendations were discussed by the
      participants and decided upon in an open vote. Consensus was defined as at least
      75% agreement. The updated guidelines will modify and improve the currently
      available guidelines in various areas, especially in therapy. For the treatment
      of chronic urticaria, the new algorithm recommends a three-step process starting
      with a standard dose of a non-sedating H1 antihistamine. If there is an
      insufficient treatment response, the dosage should be increased up to four times.
      In, therapy refractory patients, omalizumab, cyclosporine A, or montelukast are
      advised in the third step. Short-term corticosteroid treatment for a maximum of
      10 days may be considered. H2 antihistamines and dapsone, which were included in
      the previous version of the guidelines, are absent in the updated and revised
      version because of changes in the evidence level. 

PMID- 24034141
TI  - Risk factors, preemptive therapy, and antiperistaltic agents for Clostridium
      difficile infection in cancer patients.
AB  - BACKGROUND: Clostridium difficile infection (CDI) is a serious complication of
      chemotherapy including high-dose regimens with autologous stem cell
      transplantation (ASCT). Antiperistaltic agents are contraindicated in CDI and
      preemptive CDI therapy is not recommended. We assessed the incidence, risk
      factors, and outcomes of CDI in patients with newly diagnosed multiple myeloma
      (MM) receiving similar antineoplastic therapy and supportive care including
      antiperistaltic agents and preemptive CDI antibiotics for significant diarrhea.
      METHODS: A total of 303 consecutive MM patients (2004-2007) were enrolled in a
      protocol consisting of induction chemotherapy, tandem melphalan (MEL)-ASCT, and
      consolidation. Patients with grade 2-4 diarrhea were simultaneously tested for
      CDI, and initiated on antiperistaltic agents (loperamide) and preemptive anti-CDI
      therapy. Risk factors, including prior CDI and MM immunoglobulin (Ig) isotype,
      were evaluated. Multinomial logistic regression was used to compute the relative
      risk ratio (RRR) and 95% confidence intervals (CIs). RESULTS: There were 43 cases
      of CDI (14.2%) during 1529 chemotherapy courses (536 ASCT). IgA MM protected
      against CDI (RRR 0.35; 95% CI 0.13-0.93, P = 0.04) whereas CDI during first
      induction markedly increased the risk of recurrence during second induction (RRR
      = 10.94; 95% CI 1.90, 62.92, P = 0.01) and following MEL-ASCT (RRR = 6.63; 95% CI
      1.51, 29.12, P = 0.01). No CDI-related surgical intervention or death ensued
      despite use of antiperistaltic agents. CONCLUSIONS: CDI was not uncommon in
      cancer patients receiving chemotherapy. IgA myeloma appears to be protective.
      Concurrent antiperistaltic (loperamide) and preemptive CDI therapies were
      associated with excellent outcomes. Prior CDI history increased the risk for
      recurrence during successive chemotherapy courses.

PMID- 24034142
TI  - Persistent hyperparathyroidism is a major risk factor for fractures in the five
      years after kidney transplantation.
AB  - The risk of fractures after kidney transplantation is high. Hyperparathyroidism
      frequently persists after successful kidney transplantation and contributes to
      bone loss, but its impact on fracture has not been demonstrated. This
      longitudinal study was designed to evaluate hyperparathyroidism and its
      associations with mineral disorders and fractures in the 5 posttransplant years.
      We retrospectively analyzed 143 consecutive patients who underwent kidney
      transplantation between August 2004 and April 2006. The biochemical parameters
      were determined at transplantation and at 3, 12 and 60 months
      posttransplantation, and fractures were recorded. The median intact parathyroid
      hormone (PTH) level was 334 ng/L (interquartile 151-642) at the time of
      transplantation and 123 ng/L (interquartile 75-224) at 3 months. Thirty fractures
      occurred in 22 patients. The receiver operating characteristic (ROC) curve
      analysis for PTH at 3 months (area under the ROC curve = 0.711, p = 0.002) showed
      that a good threshold for predicting fractures was 130 ng/L (sensitivity = 81%,
      specificity = 57%). In a multivariable analysis, independent risk factors for
      fracture were PTH >130 ng/L at 3 months (adjusted hazard ratio [AHR] = 7.5, 95%
      CI 2.18-25.50), and pretransplant osteopenia (AHR = 2.7, 95% CI 1.07-7.26). In
      summary, this study demonstrates for the first time that persistent
      hyperparathyroidism is an independent risk factor for fractures after kidney
      transplantation.

PMID- 24034143
TI  - Patterns of uptake in a biennial faecal occult blood test screening programme for
      colorectal cancer.
AB  - AIM: The patterns of response in faecal occult blood test (FOBT) screening were
      studied. METHOD: A total of 251,578 people invited three times for faecal occult
      blood testing were categorized according to how they responded to the
      invitations, as follows: YNN, NYN, NNY, NYY, YNY, YYN, YYY or NNN (Y = response;
      N = no response). RESULTS: Overall, 163,038 (64.8%) responded at least once, and
      of those the biggest category was YYY (98,494, 60.4%). Of 1927 cancers diagnosed
      in the age group eligible for screening, there were 405 screen-detected cancers,
      529 interval cancers and 993 cancers arising in people who had not been screened
      for over 2 years (i.e. falling outside the interval cancer category). In the YYY
      group, 79 screen-detected cancers would have been missed had the members of this
      group responded YNN and 65 had they responded YYN. In the YYN group, 104
      screening cancers would have been missed if they had followed the YNN pattern. In
      most cases, the screen-detected cancers were diagnosed at the last invitation
      accepted, indicating that, after a diagnosis of cancer, further screening
      invitations were rarely accepted. Accordingly, the numbers of screen-detected and
      interval cancers were adjusted for likely pattern of response according to the
      proportion of the whole population falling into each pattern. With this
      adjustment, 40.9% of the cancers in the YYY group were screen detected compared
      with 29.3% in the YYN group and 20.7% in the YNN group (P < 0.001). Among those
      who responded once, twice and three times, the stage distribution of screen
      detected cancers was similar, indicating that the prognosis of screen-detected
      cancer is unlikely to be poorer if not detected at the first screen. CONCLUSION:
      This study is the first to examine patterns of response to screening invitations
      and confirms the importance to individuals of continuing to accept repeated
      screening invitations.

PMID- 24034144
TI  - Wall shear stress measured by phase contrast cardiovascular magnetic resonance in
      children and adolescents with pulmonary arterial hypertension.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a devastating disease with
      significant morbidity and mortality. At the macroscopic level, disease
      progression is observed as a complex interplay between mean pulmonary artery
      pressure, pulmonary vascular resistance, pulmonary vascular stiffness, arterial
      size, and flow. Wall shear stress (WSS) is known to mediate or be dependent on a
      number of these factors. Given that WSS is known to promote architectural vessel
      remodeling, it is imperative that the changes of this factor be quantified in the
      presence of PAH. METHODS: In this study, we analyzed phase contrast imaging of
      the right pulmonary artery derived from cardiovascular magnetic resonance to
      quantify the local, temporal and circumferentially averaged WSS of a PAH
      population and a pediatric control population. In addition, information about
      flow and relative area change were derived. RESULTS: Although the normotensive
      and PAH shear waveform exhibited a WSS profile which is uniform in magnitude and
      direction along the vessel circumference at systole, time-averaged WSS (2.2 +/-
      1.6 vs. 6.6 +/- 3.4 dynes/cm(2), P = 0.018) and systolic WSS (8.2 +/- 5.0 v. 20.0
      +/- 9.1 dynes/cm(2), P = 0.018) was significantly depressed in the PAH population
      as compared to the controls. BSA-indexed PA diameter was significantly larger in
      the PAH population (1.5 +/- 0.4 vs. 0.7 +/- 0.1 cm/m(2), P = 0.003). CONCLUSIONS:
      In the presence of preserved flow rates through a large PAH pulmonary artery, WSS
      is significantly decreased. This may have implications for proximal pulmonary
      artery remodeling and cellular function in the progression of PAH.

PMID- 24034146
TI  - Derivation and assessment of risk prediction models using case-cohort data.
AB  - BACKGROUND: Case-cohort studies are increasingly used to quantify the association
      of novel factors with disease risk. Conventional measures of predictive ability
      need modification for this design. We show how Harrell's C-index, Royston's D,
      and the category-based and continuous versions of the net reclassification index
      (NRI) can be adapted. METHODS: We simulated full cohort and case-cohort data,
      with sampling fractions ranging from 1% to 90%, using covariates from a cohort
      study of coronary heart disease, and two incidence rates. We then compared the
      accuracy and precision of the proposed risk prediction metrics. RESULTS: The C
      index and D must be weighted in order to obtain unbiased results. The NRI does
      not need modification, provided that the relevant non-subcohort cases are
      excluded from the calculation. The empirical standard errors across simulations
      were consistent with analytical standard errors for the C-index and D but not for
      the NRI. Good relative efficiency of the prediction metrics was observed in our
      examples, provided the sampling fraction was above 40% for the C-index, 60% for
      D, or 30% for the NRI. Stata code is made available. CONCLUSIONS: Case-cohort
      designs can be used to provide unbiased estimates of the C-index, D measure and
      NRI.

PMID- 24034147
TI  - 4-Aminoquinoline-beta-lactam conjugates: synthesis, antimalarial, and
      antitubercular evaluation.
AB  - A library of quinoline-beta-lactam-based hybrids was synthesized and tested for
      their antimalarial and antitubercular activities. The present antimalarial data
      showed the dependence of activity on the nature of linker, N-1 substituent of the
      beta-lactam ring as well as the length of alkyl chain. Most of the compounds are
      not as efficient as chloroquine in inhibiting the culture growth of Plasmodium
      falciparum W2 strain. Nevertheless, the synthesized hybrids showed better
      antitubercular activities (up to five times) compared with cephalexin (up to
      three times) and ethionamide. 

PMID- 24034148
TI  - Monitoring named entity recognition: the League Table.
AB  - BACKGROUND: Named entity recognition (NER) is an essential step in automatic text
      processing pipelines. A number of solutions have been presented and evaluated
      against gold standard corpora (GSC). The benchmarking against GSCs is crucial,
      but left to the individual researcher. Herewith we present a League Table web
      site, which benchmarks NER solutions against selected public GSCs, maintains a
      ranked list and archives the annotated corpus for future comparisons. RESULTS:
      The web site enables access to the different GSCs in a standardized format
      (IeXML). Upon submission of the annotated corpus the user has to describe the
      specification of the used solution and then uploads the annotated corpus for
      evaluation. The performance of the system is measured against one or more GSCs
      and the results are then added to the web site ("League Table"). It displays
      currently the results from publicly available NER solutions from the Whatizit
      infrastructure for future comparisons. CONCLUSION: The League Table enables the
      evaluation of NER solutions in a standardized infrastructure and monitors the
      results long-term. For access please go to http://wwwdev.ebi.ac.uk/Rebholz
      srv/calbc/assessmentGSC/. CONTACT: rebholz@ifi.uzh.ch.

PMID- 24034149
TI  - The influence of organizational context on the use of research by nurses in
      Canadian pediatric hospitals.
AB  - BACKGROUND: Organizational context is recognized as an important influence on the
      successful implementation of research by healthcare professionals. However, there
      is relatively little empirical evidence to support this widely held view.
      METHODS: The objective of this study was to identify dimensions of organizational
      context and individual (nurse) characteristics that influence pediatric nurses'
      self-reported use of research. Data on research use, individual, and contextual
      variables were collected from registered nurses (N = 735) working on 32 medical,
      surgical and critical care units in eight Canadian pediatric hospitals using an
      online survey. We used Generalized Estimating Equation modeling to account for
      the correlated structure of the data and to identify which contextual dimensions
      and individual characteristics predict two kinds of self-reported research use:
      instrumental (direct) and conceptual (indirect). RESULTS: Significant predictors
      of instrumental research use included: at the individual level; belief suspension
      implement, research use in the past, and at the hospital unit (context) level;
      culture, and the proportion on nurses possessing a baccalaureate degree or
      higher. Significant predictors of conceptual research use included: at the
      individual nurse level; belief suspension-implement, problem solving ability, use
      of research in the past, and at the hospital unit (context) level; leadership,
      culture, evaluation, formal interactions, informal interactions, organizational
      slack-space, and unit specialty. CONCLUSIONS: Hospitals, by focusing attention on
      modifiable elements of unit context may positively influence nurses' reported use
      of research. This influence of context may extend to the adoption of best
      practices in general and other innovative or quality interventions.

PMID- 24034150
TI  - Cancer of Oesophagus or Gastricus - New Assessment of Technology of
      Endosonography (COGNATE): report of pragmatic randomised trial.
AB  - BACKGROUND: Endoscopic ultrasonography is recommended for staging gastro
      oesophageal cancers, but has never been evaluated. OBJECTIVE: COGNATE (Cancer of
      Oesophagus or Gastricus - New Assessment of Technology of Endosonography)
      therefore aimed to evaluate whether adding 'endoscopic ultrasound' (EUS) to the
      usual staging algorithm changes treatment, improves (quality-adjusted) survival,
      and uses resources cost-effectively. DESIGN: Pragmatic parallel-group trial.
      Patients with gastro-oesophageal cancer received standard staging algorithms.
      Multidisciplinary teams chose provisional management plans from endoscopic
      mucosal resection, immediate surgery, surgery after chemotherapy, or chemotherapy
      and radiotherapy. We used dynamic randomisation to allocate consenting patients
      remotely by telephone in equal proportions between EUS and not. Thereafter we
      recorded changes in management plan, use of health-care resources, and three
      aspects of participant-reported quality of life: generic [measured by European
      Quality of Life - 5 Dimensions (EQ-5D)], cancer related [Functional Assessment of
      Cancer Therapy - General scale (FACT-G)] and condition-specific [FACT -
      Additional Concerns scale (FACT-AC)]. We followed participants regularly until
      death or the end of the trial - for between 1 and 4.5 years. We devised a quality
      assurance programme to maintain standards of endosonographic reporting. SETTING:
      Eight British hospitals, of which two - one Scottish teaching hospital and one
      English district general hospital - contributed 80% of participants; we combined
      the other six for analysis. PARTICIPANTS: Patients were eligible if they had a
      diagnosis of gastro-oesophageal cancer, had not started treatment, were free of
      metastatic disease, were fit for surgery (even if not planned) and had American
      Society of Anesthesiologists and World Health Organization grades of less than 3.
      INTERVENTIONS: Intervention group: standard staging algorithm plus EUS; control
      group: standard staging algorithm. MAIN OUTCOME MEASURES: Primary: quality
      adjusted survival. Secondary: survival; health-related quality of life (EQ-5D,
      FACT-G and FACT-AC scales); changes in management plan; and complete resection
      rate. Although blinding participants was neither possible nor desirable, those
      responsible for analysis remained blind until the Trial Steering Committee had
      reviewed the definitive analysis. RESULTS: We randomised 223 patients, of whom
      213 yielded enough data for primary analysis. EUS improved survival adjusted for
      generic quality of life with a hazard ratio of 0.705 [95% confidence interval
      (CI) 0.499 to 0.995], and crude survival with a hazard ratio of 0.706 (95% CI
      0.501 to 0.996). The benefits of EUS were significantly greater for those with
      poor initial quality of life, but did not differ between centres. EUS reduced net
      use of health-care resources by L2860 (95% 'bootstrapped' CI from -L2200 to
      L8000). Combining benefits and savings shows that EUS is likely to be cost
      effective, with 96% probability of achieving the National Institute for Health
      and Care Excellence criterion of costing of < L20,000 to gain a QALY. There were
      no serious adverse reactions attributable to EUS. EUS enhanced the management
      plan for many participants, increased the proportion of tumours completely
      resected from 80% (44 out of 55) to 91% (48 out of 53), and improved the survival
      of those who changed plan; although underpinning the significant differences in
      outcome, none of these process differences was itself significant. CONCLUSION:
      Endoscopic ultrasound significantly improves (quality-adjusted) survival, has the
      potential to reduce health-care resource use (not statistically significant) and
      is probably cost-effective (with 96% probability). We recommend research into the
      best time to evaluate new technologies. TRIAL REGISTRATION: ISRCTN1444215.
      FUNDING: This project was funded by the NIHR Health Technology Assessment
      programme and will be published in full in Health Technology Assessment; Vol. 17,
      No. 39. See the HTA programme website for further project information.

PMID- 24034151
TI  - Association of single-nucleotide polymorphism rs4236601 near caveolin 1 and 2
      with primary open-angle glaucoma: a meta-analysis.
AB  - BACKGROUND: To clarify the effects of a single-nucleotide polymorphism,
      rs4236601[A] near caveolin 1 and 2, on primary open-angle glaucoma (POAG) risk.
      DESIGN: Meta-analysis. PARTICIPANTS: A total of 5774 patients and 40 598 controls
      from previously reported case-control studies were included. METHODS: A
      comprehensive literature search was performed for studies published up to April
      2013. Summary odds ratios (ORs) and 95% confidence intervals (CI) were
      calculated, employing random- or fixed-effects models according to between-study
      heterogeneity. Publication bias of the literature articles was evaluated using
      funnel plots and Egger's test. MAIN OUTCOME MEASURES: OR for the effects of
      rs4236601[A] on POAG risk. RESULTS: Five eligible studies were included in this
      meta-analysis. Overall, the association between rs4236601[A] and risk for POAG
      was statistically significant (OR = 1.23, 95% CI 1.12-1.34; P < 0.001).
      Stratified analyses showed that the association between rs4236601[A] and POAG
      risk was statistically significant in Caucasians (OR = 1.25, 95% CI 1.18-1.33; P
      < 0.001) and Asians (OR = 3.33, 95% CI 1.56-7.08; P = 0.003) but not in Africans.
      Increased risks were found in age- and sex-matched studies (OR = 1.26, 95% CI
      1.14-1.40; P < 0.001), but no statistically significant risk was found in
      unmatched studies. CONCLUSIONS: This meta-analysis suggests that rs4236601[A] is
      associated with increased risk for POAG in Caucasian and Asian populations.
      However, well-designed gene-environment interaction studies and studies including
      more ethnic groups are required in further investigations.

PMID- 24034152
TI  - A prospective study on a cohort of horses and ponies selected for participation
      in the European Eventing Championship: reasons for withdrawal and predictive
      value of fitness tests.
AB  - BACKGROUND: Eventing is generally recognized as a challenging equestrian
      discipline and wastage figures for this discipline are relatively high. There is
      a need for information that provides insight into the causes of wastage and
      withdrawal from competition, for animal welfare and economic reasons. The aim of
      the present investigation was to conduct a prospective study following the entire
      national selection of event horses (n = 20) and ponies (n = 9) in the Netherlands
      that prepared for the European Championship in 2010 (ponies) and 2011 (horses),
      noting causes of withdrawal and monitoring fitness using standardized exercise
      tests (SETs), with heart rate (HR; beats/min), speed (V; m/s) and plasma lactate
      concentrations (LA; mmol/L) as measured parameters. RESULTS: In SET-I, performed
      at the beginning of the season, horses (n = 17) had a mean VLA4 (V at LA 4
      mmol/L) of 10.3 +/- 0.4 m/s with a mean V200 (V at 200 beats/min) of 11.4 +/- 0.8
      m/s and ponies (n = 9) a mean VLA4 of 7.8 +/- 0.9 m/s and V200 of 9.6 +/- 0.7
      m/s. Before SET-II, performed six weeks before the European Championship, 16/20
      horses and 6/9 ponies were withdrawn. The most common reason for withdrawal was
      locomotor injury (9/16 horses, 4/6 ponies; P < 0.001 and P = 0.011,
      respectively). Other reasons included an animal 'not meeting the competition
      criteria' (4/16 horses, 2/6 ponies) and being sold (3/16 horses). Animals were
      divided on the basis of VLA4 and recovery-HR during SET-I into good and average
      performers. Average performers were significantly more likely to be injured
      (50.0%) than good performers (0%, P = 0.05). In a subpopulation of ten horses, in
      which all condition training sessions were evaluated for HR and speed, HRpeak was
      significantly lower in horses that stayed sound (186 +/- 9 beats/min) compared
      with horses withdrawn from training and competition because of injury (201 +/- 5
      beats/min; P = 0.016). CONCLUSIONS: Of the national selection, 45% of all animals
      were unavailable for the European Championship because of locomotor injuries.
      Field tests were useful in assessing the potential injury risk, as individuals
      with better fitness indices (good performers) were less likely to become injured
      than average performers. Furthermore, monitoring of training sessions showed
      predictive value for future injuries, as horses withdrawn because of injury later
      on showed already higher peak HRs during condition training than horses that
      stayed sound. Therefore the increase in peak HR seemed to precede visible
      lameness in a horse.

PMID- 24034154
TI  - Estimation of muscle atrophy based on muscle thickness in knee surgery patients.
AB  - The purpose of this study was to establish an accurate estimation of muscle
      atrophy in the quadriceps femoris (QF) muscle group. Eighteen individuals who
      underwent meniscectomy participated in the study (nine men and nine women, mean
      age 44.4 years). Both operated and non-operated thighs were scanned by magnetic
      resonance imaging to determine the volume and thickness of the QF muscle group.
      Muscle volume was estimated using eleven axial images, and muscle thickness was
      measured at the anterior, lateral and medial regions of the proximal, mid- and
      distal thigh, respectively. A stepwise linear regression analysis was performed
      to obtain the relationship between the difference in muscle volume and the
      difference in muscle thickness between operated and non-operated limbs. There was
      no significant difference in muscle volume of the QF between operated (806.6 +/-
      220.0 cm(3) ) and non-operated (913.7 +/- 241.5 cm(3) ) limbs. Based on the
      stepwise linear regression analysis, the difference in muscle volume was
      significantly correlated with the difference in muscle thickness at the anterior
      proximal thigh and lateral mid-thigh and anterior mid-thigh (R = 0.93, P<0.01).
      In conclusion, the difference in muscle volume between operated and non-operated
      limbs can be estimated accurately by measuring muscle thickness of the QF at
      three sites: the anterior proximal thigh, the lateral mid-thigh and anterior mid
      thigh. Muscle thickness can be measured easily using imaging techniques such as
      ultrasonography. We propose that this method provides an easy and accurate
      estimate of knee surgery-induced muscle atrophy in clinical medicine. 

PMID- 24034155
TI  - The demise of the pathway may have been greatly exaggerated.

PMID- 24034153
TI  - Neuroprotection by sildenafil: neuronal networks potentiation in acute
      experimental stroke.
AB  - AIMS: Sildenafil, a phosphodiesterase type 5 inhibitor, has been found to produce
      functional recovery in ischemic rats by increasing the cGMP level and triggering
      neurogenesis. The aim of this study was to investigate further sildenafil
      mechanisms. METHODS: Male Sprague-Dawley rats underwent middle cerebral artery
      occlusion and reperfusion, followed by intraperitoneal or intravenous treatment
      of sildenafil starting 2 h later. Behavioral tests were performed on day 1 or day
      7 after reperfusion, while cerebral infarction, edema, Nissl staining, Fluoro
      Jade B staining, and electron microscopy studies were carried out 24 h
      poststroke. The cGMP-dependent Nogo-66 receptor (Nogo-R) pathway, synaptophysin,
      PSD-95/neuronal nitric oxide synthases (nNOS), brain-derived neurotrophic factor
      (BDNF)/tropomyosin-related kinase B (TrkB), and nerve growth factor
      (NGF)/tropomyosin-related kinase A (TrkA) were measured. RESULTS: Sildenafil
      enhanced neurological recovery and inhibited infarction, even following delayed
      administration 4 h after stroke onset. Furthermore, sildenafil reduced the loss
      of neurons and modulated the expressions of the cGMP-dependent Nogo-R pathway.
      Moreover, sildenafil protected the structure of synapses and mediated the
      expressions of synaptophysin, PSD-95/nNOS, BDNF/TrkB, and NGF/TrkA. CONCLUSIONS:
      Sildenafil produces significant neuroprotective effects on injured neurons in
      acute stroke, and these are mediated by the cGMP-dependent Nogo-R pathway,
      NGF/TrkA, and BDNF/TrkB.

PMID- 24034156
TI  - Philosophic reflections on the meaning of touch in nurse-patient interactions.
AB  - In this paper I examine the meaning of physical touch as it occurs in the nurse
      patient interaction. There are two aspects of the nurse-patient relationship that
      are found in most nurse-patient interactions which together have profound
      implications for nurses as practitioners and as individual human persons. The
      first is the clinical intimacy of the nurse-patient relationship where nurses
      touch, rub, smooth, clean, dress and otherwise physically interact with patients.
      The other is the existential crisis, the possibility of loss, suffering and death
      that lurks at the horizon of most, if not all, healthcare encounters. Edmund
      Husserl, Merleau-Ponty and more recently Robert Sokolowski argue that tactile
      sensations and resultant perceptions are fundamental to all sensory perception.
      Further, they argue that tactile sensation is fundamental for the ongoing
      constitution of 'my' self as a person and for the development and exercise of
      human intersubjectivity. If tactile interaction is crucial to the development of
      our very selves as persons and a significant aspect of our interaction with
      patients includes direct or observed tactile sensations and if further these
      sensations occur around the context of existential crises for our patients, then
      nurse's very selves as persons are being challenged by these interactions. Here,
      then I examine the philosophical argument for the role of tactile sensations in
      our human development and briefly look at contemporary neurophysiologic research
      that supports this philosophical account. I then suggest ways such physical
      intimacy can lead to a strengthening or weakening of the person of the nurse and
      the nursing interaction and end with some thoughts about ways to support nurses
      in these activities. 

PMID- 24034157
TI  - Some may beg to differ: individual beliefs and group political claims.
AB  - While nurses can and do behave as intentional political agents, claims that
      nurses collectively do (empiric), should (normative) or must (regulatory) act to
      advance political objectives lack credibility. This paper challenges the
      coherence and legitimacy of political demands placed upon nurses. It is not
      suggested that nurses ought not to contribute to political discourse and
      activity. That would be foolish. However, the idea that nursing can own or
      exhibit a general political will is discarded. It is suggested that to protect
      and advance political discussion, to aid explanatory adequacy and clarity, the
      form in which nursing associates itself with political claims merits critical
      appraisal. Thus significant numbers of nurses probably reject or disagree with
      many of the political claims that attach to them--claims often made on their
      behalf. More specifically, the individual beliefs and goals of nurses can be in
      conflict with the political pronouncements of nursing scholars and organizations
      (group agents). It is proposed that nurses need not share substantive normative
      beliefs/goals and, if this proposal holds, group descriptors such as 'nurses' and
      'nursing' cannot meaningfully or easily attach to political claims. Shared value
      theory is linked to the fallacy of composition and the concept of collective
      ascription error is introduced to explore the implausibility of using group
      descriptors such as 'nurses' and 'nursing' to refer to the beliefs/goals of all
      nurses.

PMID- 24034158
TI  - Nursing opinion leadership: a preliminary model derived from philosophic theories
      of rational belief.
AB  - Opinion leaders are informal leaders who have the ability to influence others'
      decisions about adopting new products, practices or ideas. In the healthcare
      setting, the importance of translating new research evidence into practice has
      led to interest in understanding how opinion leaders could be used to speed this
      process. Despite continued interest, gaps in understanding opinion leadership
      remain. Agent-based models are computer models that have proven to be useful for
      representing dynamic and contextual phenomena such as opinion leadership. The
      purpose of this paper is to describe the work conducted in preparation for the
      development of an agent-based model of nursing opinion leadership. The aim of
      this phase of the model development project was to clarify basic assumptions
      about opinions, the individual attributes of opinion leaders and characteristics
      of the context in which they are effective. The process used to clarify these
      assumptions was the construction of a preliminary nursing opinion leader model,
      derived from philosophical theories about belief formation. 

PMID- 24034159
TI  - Understanding 'caring' through biopolitics: the case of nurses under the Nazi
      regime.
AB  - These days, discussions of what might be the 'essence' or the 'core' of nursing
      and nursing practice sooner or later end in a discussion about the concept of
      care. Most of the 'newer' nursing theories use this concept as a theoretical core
      concept. Even though these theoretical approaches use the concept of care with
      very different philosophical foundations and theoretical consistency, they concur
      in defining care as the essence of nursing and thereby glorify goodness as the
      decisive characteristic of nursing. These theoretical approaches neglect the fact
      that nursing is above all a profession with a societal task and is characterized
      by an asymmetrical power relation between nurses and their patients. Based on the
      results of a research project that analysed the role nurses played in the killing
      of psychiatric patients in Germany during the Nazi regime, I demonstrate that an
      approach based on the concept of care is not able to explain how nurses were able
      to commit crimes of such atrocity. These crimes were bound to an emotional
      investment that sustained the production of 'life unworthy of living'. In the
      case of nurses under the Nazi regime, certainly a kind of sadism was at issue
      that can only be explained if we recognize that the social bond is characterized
      by a certain tension; 'goodness' that caring theories assign to the social bond
      always coexists with the capacity for destruction. Using the Foucauldian
      theoretical framework of biopower and biopolitics enables one to analyse violence
      and power as integral parts of nurses' practice. Seen from this perspective, the
      killing of patients was part of a biopolitical programme and not a relapse into
      barbarism. The concept of care obscures the political agenda of nursing and does
      not provide a critical and political framework to analysing nursing practice. 

PMID- 24034160
TI  - Domestic abuse as a transgressive practice: understanding nurses' responses
      through the lens of abjection.
AB  - Domestic abuse is a worldwide public health issue with long-term health and
      social consequences. Nurses play a key role in recognizing and responding to
      domestic abuse. Yet there is considerable evidence that their responses are often
      inappropriate and unhelpful, such as trivializing or ignoring the abuse.
      Empirical studies have identified several reasons why nurses' responses are
      sometimes wanting. These include organizational constraints, e.g. lack of time
      and privacy; and interpersonal factors such as fear of offending women and lack
      of confidence. We propose, however, that these factors present only a partial
      explanation. Drawing on the work of Julia Kristeva, we suggest that alternative
      understandings may be derived through applying the concept of abjection.
      Abjection is a psychological defence against any threat (the abject) to the clean
      and proper self that results in rejection of the abject. Using examples from our
      own domestic abuse research, we contend that exposure of nurses to the horror of
      domestic abuse evokes a state of abjection. Domestic abuse (the abject)
      transgresses established social boundaries of clean and proper. Thus when exposed
      to patients' and clients' experiences of it, some nurses subconsciously reject
      domestic abuse as a possibility (abjection). They do this to protect themselves
      from the horror of the act, but in so doing, render themselves unable to
      formulate appropriate responses. Rather than understanding the practice of some
      nurses as wilfully neglectful or ignorant, we argue that through a state of
      abjection, they are powerless to act. This does not refute existing evidence
      about nurses' responses to domestic abuse. Rather, as a relatively unknown
      concept in nursing, abjection provides an additional explanatory layer that
      accounts for why some nurses respond the way they do. Crucially, it elucidates
      the need for nurses to be supported emotionally when faced with the transgressive
      practice of abuse. 

PMID- 24034162
TI  - Hypocalcaemia after an occult calcium channel blocker overdose: a case report and
      literature review.
AB  - Hypocalcaemia is a rare complication of calcium channel blocker overdose, having
      been reported only once previously (J Toxicol Clin Toxicol, 1992, 30, 309). In
      this article, we report a case of a 37-year-old woman who developed hypocalcaemia
      after a verapamil overdose, review the literature and propose a mechanism for
      this rare finding. 

PMID- 24034163
TI  - Use of Sysmex XE-2100 and XE-5000 hematology analyzers for the diagnosis of
      malaria in a nonendemic country (France).
AB  - INTRODUCTION: Most studies dealing with automated hematology analyzers (HAs) and
      malaria diagnosis are conducted in endemic countries. METHODS: We retrospectively
      studied cell blood counts (CBCs) performed with Sysmex XE-2100 and XE-5000 HAs in
      our center (Angers, France) regarding 67 patients returning from endemic areas
      and infected with various Plasmodium species. RESULTS: In 83% of infected samples
      with Plasmodium vivax (Pv), ovale (Po), or malariae (Pm), extra clouds of dots
      were present in neutrophil and/or eosinophil area(s) on routine differential
      (DIFF) scattergrams. In contrast, samples infected with Plasmodium falciparum
      (Pf) failed to show such DIFF scattergrams, or any other suggesting malaria
      infection (0/ 49 pts). Abnormal areas from DIFF scattergrams were related to the
      presence of mature schizonts and gametocytes, undestroyed by lysis agent, the
      latter not observed in Pf-infected patients from our series. The internal
      parameter WBC[DIFF] - WBC[BASO] raised in parallel to parasitemia in Pv, Po, and
      Pm samples but could not be used as a surrogate for parasitemia. In Pf infection,
      reticulocyte/ immature reticulocyte fraction (IRF) ratio showed a significant
      correlation with parasitemia (P < 0.05). A diagnostic model developed for Pf in
      endemic countries showed sensitivity of 77%. CONCLUSION: Using SYSMEX analyzers,
      Pv, Po, and Pm infections are easy to ascertain as DIFF scattergrams are almost
      specific (specificity = 99.9%). Pf infection diagnosis by CBC may be a more
      promising tool.

PMID- 24034164
TI  - Involvement of histone modifications in plant abiotic stress responses.
AB  - As sessile organisms, plants encounter various environmental stimuli including
      abiotic stresses during their lifecycle. To survive under adverse conditions,
      plants have evolved intricate mechanisms to perceive external signals and respond
      accordingly. Responses to various stresses largely depend on the plant capacity
      to modulate the transcriptome rapidly and specifically. A number of studies have
      shown that the molecular mechanisms driving the responses of plants to
      environmental stresses often depend on nucleosome histone post-translational
      modifications including histone acetylation, methylation, ubiquitination, and
      phosphorylation. The combined effects of these modifications play an essential
      role in the regulation of stress responsive gene expression. In this review, we
      highlight our current understanding of the epigenetic mechanisms of histone
      modifications and their roles in plant abiotic stress response.

PMID- 24034166
TI  - Leaf-associated fungal diversity in acidified streams: insights from combining
      traditional and molecular approaches.
AB  - We combined microscopic and molecular methods to investigate fungal assemblages
      on alder leaf litter exposed in the benthic and hyporheic zones of five streams
      across a gradient of increasing acidification for 4 weeks. The results showed
      that acidification and elevated Al concentrations strongly depressed sporulating
      aquatic hyphomycetes diversity in both zones of streams, while fungal diversity
      assessed by denaturing gradient gel electrophoresis (DGGE) appeared unaffected.
      Clone library analyses revealed that fungal communities on leaves were dominated
      by members of Ascomycetes and to a lesser extent by Basidiomycetes and
      Chytridiomycetes. An important contribution of terrestrial fungi was observed in
      both zones of the most acidified stream and in the hyporheic zone of the
      reference circumneutral stream. The highest leaf breakdown rate was observed in
      the circumneutral stream and occurred in the presence of both the highest
      diversity of sporulating aquatic hyphomycetes and the highest contribution to
      clone libraries of sequences affiliated with aquatic hyphomycetes. Both methods
      underline the major role played by aquatic hyphomycetes in leaf decomposition
      process. Our findings also bring out new highlights on the identity of leaf
      associated fungal communities and their responses to anthropogenic alteration of
      running water ecosystems. 

PMID- 24034167
TI  - Donor age and early graft failure after lung transplantation: a cohort study.
AB  - Lungs from older adult organ donors are often unused because of concerns for
      increased mortality. We examined associations between donor age and transplant
      outcomes among 8860 adult lung transplant recipients using Organ Procurement and
      Transplantation Network and Lung Transplant Outcomes Group data. We used
      stratified Cox proportional hazard models and generalized linear mixed models to
      examine associations between donor age and both 1-year graft failure and primary
      graft dysfunction (PGD). The rate of 1-year graft failure was similar among
      recipients of lungs from donors age 18-64 years, but severely ill recipients
      (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs
      from donors age 56-64 years had increased rates of 1-year graft failure (p-values
      for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors
      <18 and >=65 years had increased rates of 1-year graft failure (adjusted hazard
      ratio [HR] 1.23, 95% CI 1.01-1.50 and adjusted HR 2.15, 95% CI 1.47-3.15,
      respectively). Donor age was not associated with the risk of PGD. In summary, the
      use of lungs from donors age 56 to 64 years may be safe for adult candidates
      without a high LAS and the use of lungs from pediatric donors is associated with
      a small increase in early graft failure.

PMID- 24034169
TI  - Field efficacy of nonpathogenic Streptomyces species against potato common scab.
AB  - AIMS: The primary objective of these experiments was to reduce pathogenicity and
      virulence of endemic soil pathogenic Streptomyces strains that cause potato
      common scab (CS) using nonpathogenic Streptomyces strains to suppress CS in a
      field situation. METHODS AND RESULTS: Nonpathogenic Streptomyces strains that had
      shown potential for mitigating CS in greenhouse assays were used in Michigan and
      Pennsylvania fields known to have high CS disease pressure. Five biocontrol (BC)
      strains and three potato cultivars were used in 2009, and three BC strains and
      three cultivars were used in 2010 in each location. The effects of BC strains on
      CS disease incidence and severity differed between locations, years and potato
      cultivars. When overall means of individual BC treatments were compared with
      nontreated controls, CS incidence and severity were decreased by all BC strains
      in PA2009, PA2010 and MI2010, particularly in cultivar 'Yukon Gold' in MI.
      Biocontrol treatments also significantly shifted the proportions of superficial,
      raised and pitted lesion types in some cultivar/biocontrol treatment
      combinations. CONCLUSIONS: All BC strains significantly reduced CS incidence and
      severity on 'Yukon Gold' in three of four trials, and one BC strain significantly
      improved the lesion severity profile in cultivar 'Atlantic'. No BC strain
      significantly reduced CS incidence and severity on all potato cultivars in the
      different years and locations. SIGNIFICANCE AND IMPACT OF THE STUDY: Several
      nonpathogenic Streptomyces strains showed potential to reduce CS incidence and
      severity on two important potato-chipping cultivars in the field. These results
      can be further applied to reduce CS disease severity in potatoes.

PMID- 24034168
TI  - Novel insight into the detailed myocardial motion and deformation of the rodent
      heart using high-resolution phase contrast cardiovascular magnetic resonance.
AB  - BACKGROUND: Phase contrast velocimetry cardiovascular magnetic resonance (PC-CMR)
      is a powerful and versatile tool allowing assessment of in vivo motion of the
      myocardium. However, PC-CMR is sensitive to motion related artifacts causing
      errors that are geometrically systematic, rendering regional analysis of
      myocardial function challenging. The objective of this study was to establish an
      optimized PC-CMR method able to provide novel insight in the complex regional
      motion and strain of the rodent myocardium, and provide a proof-of-concept in
      normal and diseased rat hearts with higher temporal and spatial resolution than
      previously reported. METHODS: A PC-CMR protocol optimized for assessing the
      motion and deformation of the myocardium in rats with high spatiotemporal
      resolution was established, and ten animals with different degree of cardiac
      dysfunction underwent examination and served as proof-of-concept. Global and
      regional myocardial velocities and circumferential strain were calculated, and
      the results were compared to five control animals. Furthermore, the global strain
      measurements were validated against speckle-tracking echocardiography, and inter-
      and intrastudy variability of the protocol were evaluated. RESULTS: The presented
      method allows assessment of regional myocardial function in rats with high level
      of detail; temporal resolution was 3.2 ms, and analysis was done using 32
      circumferential segments. In the dysfunctional hearts, global and regional
      function were distinctly altered, including reduced global peak values, increased
      regional heterogeneity and increased index of dyssynchrony. Strain derived from
      the PC-CMR data was in excellent agreement with echocardiography (r = 0.95, p <
      0.001; limits-of-agreement -0.02 +/- 3.92%strain), and intra- and interstudy
      variability were low for both velocity and strain (limits-of-agreement, radial
      motion: 0.01 +/- 0.32 cm/s and -0.06 +/- 0.75 cm/s; circumferential strain: -0.16
      +/- 0.89%strain and -0.71 +/- 1.67%strain, for intra- and interstudy,
      respectively). CONCLUSION: We demonstrate, for the first time, that PC-CMR
      enables high-resolution evaluation of in vivo circumferential strain in addition
      to myocardial motion of the rat heart. In combination with the superior geometric
      robustness of CMR, this ultimately provides a tool for longitudinal studies of
      regional function in rodents with high level of detail.

PMID- 24034170
TI  - Declining cardiopulmonary exercise capacity is not associated with worsening
      systolic systemic ventricular dysfunction in adults with transposition of great
      arteries after atrial switch operation.
AB  - BACKGROUND/OBJECTIVE: Cardiopulmonary exercise capacity is often reduced in
      patients with transposition of the great arteries after atrial switch operation.
      Reduced exercise capacity may be caused by deterioration of systemic right
      ventricular function over time. This study analyzed serial changes in systemic
      right ventricular function and cardiopulmonary exercise capacity in young adults
      with transposition of the great arteries after atrial redirection surgery.
      METHODS: Twenty-one patients (37% female, mean age 23.2 +/- 3.3, mean age at
      surgery 12.8 +/- 14 years) with transposition of the great arteries after atrial
      switch operation were included in this study. Patients were followed up for a
      mean period of 39.6 +/- 13.1 months. Exercise capacity expressed as peak VO2 max,
      systemic right ventricular function and subpulmonary left ventricular function
      assessed by cardiac magnetic resonance imaging and NT-proBNP levels were obtained
      at baseline and follow-up. Changes in peak VO2 max were correlated to changes in
      cardiac magnetic resonance imaging and NT-proBNP levels. RESULTS: Baseline peak
      VO2 max decreased significantly (28.31 +/- 5.80 mL/kg/min vs. 25.17 +/- 5.71
      mL/kg/min, P = .005) on follow-up. Cardiac magnetic resonance imaging parameters
      of systemic right ventricular ejection fraction as well as subpulmonary left
      ventricular ejection fraction remained unchanged (44.68 +/- 6.59% vs. 45.65 +/-
      9.60%, P = .54, 60.18 +/- 6.29% vs. 61.52 +/- 5.30%, P = .35). NT-proBNP levels
      did not increase (211.7 +/- 85.7 ng/mL vs. 261.2 +/- 182.2 ng/mL, P = .16).
      CONCLUSIONS: After atrial switch operation for transposition of the great
      arteries we observed a declining functional exercise capacity. This was not
      associated with worsening systemic right ventricular function, suggesting that
      other factors are contributing to the decline in physical exercise capacity.

PMID- 24034171
TI  - Brucellosis in a renal transplant recipient.
AB  - Brucellosis is one of the most common systemic zoonotic diseases transmitted by
      consumption of unpasteurized dairy products or by occupational contact with
      infected animals. Brucellosis is rare in renal transplant recipients. Only 3
      cases have been reported in the literature. We report a case of brucellosis with
      hematologic and hepatobiliary complications in a patient 3 years after renal
      transplantation. The mean time from transplantation to the diagnosis of
      brucellosis in these 4 reported patients was 5.1 years (range 17 months to 13
      years). All patients had fever and constitutional symptoms, and all attained
      clinical cure after combination antibiotic therapy. Given the small number of
      patients, further study is needed to identify the characteristics of brucellosis
      in renal transplant recipients. Drug interactions and acute renal failure
      developed in our patient during antibiotic treatment. Therefore, we should
      monitor the levels of immunosuppressive agents frequently. Several studies have
      shown in vitro susceptibilities of Brucella melitensis to tigecycline. In our
      patient, fever finally subsided after tigecycline administration. The minimum
      inhibitory concentration of tigecycline using Etest was 0.094 MUg/mL. Tigecycline
      may be a potential option for treatment of brucellosis in the setting of
      transplantation. 

PMID- 24034172
TI  - Omental pedicle flaps following proctectomy: a systematic review.
AB  - AIM: Abdominoperineal excision (APR) for cancer carries significant morbidity of
      the perineal wound. An omental pedicle graft has been used to fill the pelvis and
      limit attendant complications after radical extirpation of the anorectum. A
      review of the literature was conducted to determine whether omentoplasty
      following APR reduces perineal wound complications. METHOD: Three major databases
      (PubMed, MEDLINE and the Cochrane Library) were searched. The review included
      original articles reporting outcomes after APR and omentoplasty from January 1950
      to July 2012. RESULTS: Fourteen studies involving 891 patients (mean age 61
      years, 59.8% men) were included. Median follow-up was 13.5 months. A variety of
      omentoplasty techniques added a median of 20 min to the operating time. The mean
      rate of primary wound healing was 66.8%, time to wound healing 24 days and
      weighted mean wound infection rate 14.4% with omentoplasty compared with 50.1%,
      79 days and 18.5% in patients having no omentoplasty. CONCLUSION: Omental
      mobilization, transfer and buttressing of primary perineal repair following
      proctectomy reduces perineal wound morbidity with minimal additional operating
      time or flap-associated morbidity.

PMID- 24034173
TI  - Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS): rationale
      and design for meta-analyses of individual patient data of randomized controlled
      trials that evaluate the effect of physical activity and psychosocial
      interventions on health-related quality of life in cancer survivors.
AB  - BACKGROUND: Effective interventions to improve quality of life of cancer
      survivors are essential. Numerous randomized controlled trials have evaluated the
      effects of physical activity or psychosocial interventions on health-related
      quality of life of cancer survivors, with generally small sample sizes and modest
      effects. Better targeted interventions may result in larger effects. To realize
      such targeted interventions, we must determine which interventions that are
      presently available work for which patients, and what the underlying mechanisms
      are (that is, the moderators and mediators of physical activity and psychosocial
      interventions). Individual patient data meta-analysis has been described as the
      'gold standard' of systematic review methodology. Instead of extracting aggregate
      data from study reports or from authors, the original research data are sought
      directly from the investigators. Individual patient data meta-analyses allow for
      adequate statistical analysis of intervention effects and moderators of such
      effects.Here, we report the rationale and design of the Predicting OptimaL cAncer
      RehabIlitation and Supportive care (POLARIS) Consortium. The primary aim of
      POLARIS is 1) to conduct meta-analyses based on individual patient data to
      evaluate the effect of physical activity and psychosocial interventions on the
      health-related quality of life of cancer survivors; 2) to identify important
      demographic, clinical, personal, or intervention-related moderators of the
      effect; and 3) to build and validate clinical prediction models identifying the
      most relevant predictors of intervention success. METHODS/DESIGN: We will invite
      investigators of randomized controlled trials that evaluate the effects of
      physical activity and/or psychosocial interventions on health-related quality of
      life compared with a wait-list, usual care or attention control group among adult
      cancer survivors to join the POLARIS consortium and share their data for use in
      pooled analyses that will address the proposed aims. We are in the process of
      identifying eligible randomized controlled trials through literature searches in
      four databases. To date, we have identified 132 eligible and unique trials.
      DISCUSSION: The POLARIS consortium will conduct the first individual patient data
      meta-analyses in order to generate evidence essential to targeting physical
      activity and psychosocial programs to the individual survivor's characteristics,
      capabilities, and preferences. REGISTRATION PROSPERO: International prospective
      register of systematic reviews, CRD42013003805.

PMID- 24034174
TI  - Mapping the disease gene in two congenital motor nystagmus families.

PMID- 24034175
TI  - Accurate identification of the six human Plasmodium spp. causing imported
      malaria, including Plasmodium ovale wallikeri and Plasmodium knowlesi.
AB  - BACKGROUND: Accurate identification of Plasmodium infections in non-endemic
      countries is of critical importance with regard to the administration of a
      targeted therapy having a positive impact on patient health and management and
      allowing the prevention of the risk of re-introduction of endemic malaria in such
      countries. Malaria is no longer endemic in Italy where it is the most commonly
      imported disease, with one of the highest rates of imported malaria among
      European non-endemic countries including France, the UK and Germany, and with a
      prevalence of 24.3% at the University Hospital of Parma. Molecular methods showed
      high sensitivity and specificity and changed the epidemiology of imported malaria
      in several non-endemic countries, highlighted a higher prevalence of Plasmodium
      ovale, Plasmodium vivax and Plasmodium malariae underestimated by microscopy and,
      not least, brought to light both the existence of two species of P. ovale
      (Plasmodium ovale curtisi and Plasmodium ovale wallikeri) and the infection in
      humans by Plasmodium knowlesi, otherwise not detectable by microscopy. METHODS:
      In this retrospective study an evaluation of two real-time PCR assays able to
      identify P. ovale wallikeri, distinguishing it from P. ovale curtisi, and to
      detect P. knowlesi, respectively, was performed applying them on a subset of 398
      blood samples belonging to patients with the clinical suspicion of malaria.
      RESULTS: These assays revealed an excellent analytical sensitivity and no cross
      reactivity versus other Plasmodium spp. infecting humans, suggesting their
      usefulness for an accurate and complete diagnosis of imported malaria. Among the
      128 patients with malaria, eight P. ovale curtisi and four P. ovale wallikeri
      infections were detected, while no cases of P. knowlesi infection were observed.
      DISCUSSION AND CONCLUSIONS: Real-time PCR assays specific for P. ovale wallikeri
      and P. knowlesi were included in the panel currently used in the University
      Hospital of Parma for the diagnosis of imported malaria, accomplishing the goal
      of adhering to the recommendations of the World Health Organization to countries
      that are malaria-free to include the improvement of the early diagnosis of all
      cases of imported malaria.

PMID- 24034176
TI  - Factors influencing pharmacists' adoption of prescribing: qualitative application
      of the diffusion of innovations theory.
AB  - BACKGROUND: In 2007, Alberta became the first Canadian jurisdiction to grant
      pharmacists a wide range of prescribing privileges. Our objective was to
      understand what factors influence pharmacists' adoption of prescribing using a
      model for the Diffusion of Innovations in healthcare services. METHODS:
      Pharmacists participated in semi-structured telephone interviews to discuss their
      prescribing practices and explore the facilitators and barriers to
      implementation. Pharmacists working in community, hospital, PCN, or other
      settings were selected using a mix of random and purposive sampling. Two
      investigators independently analyzed each transcript using an Interpretive
      Description approach to identify themes. Analyses were informed by a model
      explaining the Diffusion of Innovations in health service organizations. RESULTS:
      Thirty-eight participants were interviewed. Prescribing behaviours varied from
      non-adoption through to product, disease, and patient focused use of prescribing.
      Pharmacists' adoption of prescribing was dependent on the innovation itself,
      adopter, system readiness, and communication and influence. Adopting pharmacists
      viewed prescribing as a legitimization of previous practice and advantageous to
      instrumental daily tasks. The complexity of knowledge required for prescribing
      increased respectively in product, disease and patient focused prescribing
      scenarios. Individual adopters had higher levels of self-efficacy toward
      prescribing skills. At a system level, pharmacists who were in practice settings
      that were patient focused were more likely to adopt advanced prescribing
      practices, over those in product-focused settings. All pharmacists stated that
      physician relationships impacted their prescribing behaviours and individual
      pharmacists' decisions to apply for independent prescribing privileges.
      CONCLUSIONS: Diffusion of Innovations theory was helpful in understanding the
      multifaceted nature of pharmacists' adoption of prescribing. The characteristics
      of the prescribing model itself which legitimized prior practices, the model of
      practice in a pharmacy setting, and relationships with physicians were prominent
      influences on pharmacists' prescribing behaviours.

PMID- 24034177
TI  - The impact of neighborhood deprivation on patients' unscheduled out-of-hours
      healthcare seeking behavior: a cross-sectional study.
AB  - BACKGROUND: The use of unscheduled out of hours medical care is related to the
      social status of the patient. However, the social variance in the patient's
      preference for a hospital based versus a primary care based facility, and the
      impact of specific patient characteristics such as the travel distance to both
      types of facilities is unclear. This study aims to determine the social gradient
      in emergency care seeking behavior (consulting the emergency department (ED) in a
      hospital or the community-based Primary Care Center (PCC)) taking into account
      patient characteristics including the geographical distance from the patient's
      home to both services. METHODS: A cross-sectional study, including 7,723 patients
      seeking out-of-hours care during 16 weekends and 2 public holidays was set up in
      all EDs and PCCs in Ghent, Belgium. Information on the consulted type of service,
      and neighborhood deprivation level was collected, but also the exact geographical
      distance from the patient's home to both types of services, and if the patient
      has a regular GP. RESULTS: Patients living in a socially deprived area have a
      higher propensity to choose a hospital-based ED than their counterparts living in
      more affluent neighborhoods. This social difference persists when taking into
      account distance to both services, having a regular GP, and being hospitalized or
      not. The impact of the distance between the patient's home address and the
      location of both types of services on the patient's choice of service is rather
      small. CONCLUSIONS: Initiatives aiming to lead patients more to PCC by penalizing
      inappropriate ED use might increase health inequity when they are not twinned
      with interventions improving the access to primary care services and tackling the
      underlying mechanisms of patients' emergency care seeking behavior. Further
      research exploring the impact of out-of-hours care organization (gatekeeping,
      payment systems, ...) and the patient's perspectives on out-of-hours care
      services is needed.

PMID- 24034178
TI  - Nitric oxide and carbon monoxide diffusing capacity after a 1-h oxygen dive to 9
      m of sea water.
AB  - INTRODUCTION: To prevent extensive pulmonary lesions in submerged oxygen divers
      lung function like the forced vital capacity (FVC) or the diffusing capacity for
      carbon monoxide (DL,co) are used to monitor pulmonary oxygen toxicity (POT). As
      the diffusing capacity for nitric oxide (DL,no) measures more accurately the
      membrane diffusing capacity compared to DL,co we hypothesized that DL,no is
      superior in monitoring the onset of physiological changes indicative of POT as
      compared to DL,co or FVC. METHOD: 26 healthy divers (mean age 30.7 +/- 6.2 years)
      made two submerged dives to 190 kPa for 1 h on two randomized separate days,
      whilst breathing 100% oxygen or compressed air. FVC, DL,no, DL,co and alveolar
      volume (VA ) were measured 6 times during a 26-h period. RESULTS: Up to 8 h no
      significant differences in outcomes were found between the oxygen and air dives.
      However, at 8 h after the oxygen dives there was a significant reduction in
      DL,no, DL,co and VA as compared with air dives. In contrast, the reduction in FVC
      was significantly greater after the air dive. At 22 h there were no longer
      differences in outcomes between the dives. CONCLUSIONS: These data show that
      DL,no and DL,co are significantly reduced 8 h after submerged oxygen dives as
      compared to similar air dives. Together with the reduction in VA this may be
      indicative of interstitial edema as an early sign of POT. Our data warrant
      validation of the superiority of DL,no and DL,co over FVC in the practical
      monitoring of divers.

PMID- 24034179
TI  - Nuclear Factor-kappaB-Mediated Endothelin Receptor Up-Regulation Increases Renal
      Artery Contractility in Rats.
AB  - Increased renal artery contractility leads to renal vasospasm and ischaemia as
      well as kidney damage. This study was designed to examine the hypothesis that
      organ culture of renal arteries induces transcriptional up-regulation of
      endothelin type A (ETA ) and type B2 (ETB2 ) receptors in the smooth muscle cells
      via activation of nuclear factor-kappaB (NF-kappaB) and subsequently increases
      renal artery contractility. Rat renal artery segments were organ-cultured for 6
      or 24 hr to increase endothelin receptor-mediated contraction. To dissect
      molecular mechanisms involved in this process, inhibitors for NF-kappaB
      signalling pathway (MG-132 and BMS345541), transcription (actinomycin D) and
      translation (cycloheximide) were used during organ culture. Endothelin receptors
      were studied using a sensitive myograph (functional contractility), real-time PCR
      (mRNA analysis) and immunohistochemistry (protein localization). Compared with
      fresh segments, contractile responses to endothelin-1 (non-selective endothelin
      receptor agonist) and sarafotoxin 6c (selective ETB receptor agonist) were
      significantly increased in the segments after 24 hr of organ culture; ETB2
      receptor-mediated maximal contraction increased from 2.7 +/- 0.5 to 135.3 +/- 5.1
      (p < 0.001), and potency (pEC50 ) of ETA receptor agonist increased from 8.20 +/-
      0.04 to 8.72 +/- 0.07 (p < 0.001). This was in parallel with increased
      corresponding mRNA and protein expression for ETA and ETB2 receptors. BMS345541,
      MG-132, actinomycin D or cyclohexamide, respectively, suppressed the up
      regulation of ETA and ETB2 receptors. Immunostaining performed with specific
      antibody showed that IkappaB was phosphorylated during organ culture. In
      conclusion, activation of NF-kappaB mediates up-regulation of ETA and ETB2
      receptors and subsequently increases renal artery contractility, which may
      contribute to renal vasospasm and ischaemia as well as kidney damage. 

PMID- 24034180
TI  - A case of de novo aleukemic mast cell leukemia without c-KIT mutations in exons 8
      and 17.

PMID- 24034181
TI  - A systematic review of sevoflurane and isoflurane minimum alveolar concentration
      in domestic cats.
AB  - OBJECTIVE: The purpose of this systematic review is to summarize the results of
      studies which have determined the minimum alveolar concentration (MAC) of
      isoflurane and sevoflurane in domestic cats. STUDY DESIGN: Systematic review.
      ANIMALS: Cats. METHODS USED: A comprehensive search of research literature was
      performed without language restriction. The search utilized the Pubmed, Google
      Scholar, and CAB Abstracts electronic databases using a combination of free text
      terms 'Minimum alveolar concentration', 'sevoflurane', 'isoflurane',
      'anesthetic', 'cat', 'cats' or 'feline'. The search was conducted from November
      2010 to June 2012. RESULTS: The MAC for isoflurane ranged from 1.20 +/- 0.13% to
      2.22 +/- 0.35% and the MAC for sevoflurane ranged from 2.5 +/- 0.2% to 3.95 +/-
      0.33%. The average MAC for isoflurane was 1.71 +/- 0.07% and for sevoflurane was
      3.08 +/- 0.4%. CONCLUSIONS & CLINICAL RELEVANCE: The average MAC for isoflurane
      was 1.71 +/- 0.07% and for sevoflurane was 3.08 +/- 0.4%. Methodology differed
      among studies, and particular attention should be paid in the future to
      appropriate reporting of methods to allow sound conclusions to be made from the
      results.

PMID- 24034182
TI  - Honouring social accountability: a moral responsibility of the medical
      profession.

PMID- 24034183
TI  - Variations in cerebral arterial circle of Willis in adult Pakistani population.
AB  - OBJECTIVE: To identify the anatomical variations in cerebral arterial circle of
      Willis. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department
      of Anatomy, University of Health Sciences, Lahore, from February 2009 to January
      2010. METHODOLOGY: Human brains were removed from fifty-one consecutive cadavers
      at the time of autopsy from Forensic Department, King Edward Medical University,
      Lahore, to observe anatomical variations in the cerebral arterial circle
      regarding its completeness, pattern and symmetry. The individual cerebral vessels
      were also noted for the presence, origin, caliber and symmetry. Pictures from
      each dissection, showing the complete circle were taken. The variations of the
      circle as whole and segmental variations were studied and described in
      percentage. RESULTS: Thirty-seven (72.5%) of the 51 (100%) cerebral arterial
      circles were complete; 15 subjects (29.4%) had typical configuration; 25 (49%)
      had symmetrical arrangement and 39 subjects (76.4%) had different types of
      variations in their component vessels. Variations were most common in the
      posterior communicating artery followed by anterior communicating artery, pre
      communicating segments of the posterior cerebral and pre-communicating segments
      of anterior cerebral arteries. No circle was found with aneurysm. CONCLUSION:
      Different variations in the formation of circle of Willis and in its component
      vessels are common in the local adult population of Pakistan. These should be
      taken into consideration during angiographic evaluation and neurosurgical
      procedures on the anterior circulation.

PMID- 24034184
TI  - Frequency and risk factors in the post-ERCP pancreatitis in a tertiary care
      centre.
AB  - OBJECTIVE: To evaluate the frequency and associated factors in the post
      endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. STUDY DESIGN:
      Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Endoscopy Suite of
      Surgical Unit IV, Civil Hospital, Karachi, from December 2009 to November 2010.
      METHODOLOGY: Patients undergoing ERCP were included. Patients who had presented
      with pancreatitis or raised amylase levels before procedure or patients who had
      previous history of surgery on the biliary or pancreatic systems were excluded
      from the study. Pearson chi-square and Fisher's exact test were used for
      qualitative data and t-test for quantitative data. Significance was taken as p 2
      0.05. Odds ratio was calculated for the qualitative data using 95% confidence
      interval. RESULTS: Age of the study population ranged from 9 to 90 years (mean
      age 46.5 +/- 14.94 years, median 45 years). Male to female ratio was 1:1.87.
      Pancreatitis was seen in 18 patients (3.6%), mild in 15 (3%), moderate in one
      (0.2%) and severe in 2 (0.4%). Mean amylase level at 4 hours and 24 hours was
      280.93 +/- 539.13 and 168.83 +/- 338.34 respectively. Pancreatitis was seen in
      15/326 (4.6%) females and 3/174 (1.72%) males. Statistically significant
      increased risk for pancreatitis was seen in difficult cannulation (9.8%, p =
      0.006), prolonged cannulation time (7.6 minute, p = 0.002), pancreatic duct
      cannulation (13.7%, p = 0.001) and pancreatic duct contrast injection (13.4%, p <
      0.001). CONCLUSION: The frequency of post-ERCP pancreatitis was 3.6%. Difficult
      cannulation, pancreatic duct cannulation, pancreatic duct contrast injection and
      balloon sphincteroplasty were associated with higher frequency of post-ERCP
      pancreatitis. Reuse of ERCP accessories poses no additional risk to the frequency
      of pancreatitis.

PMID- 24034185
TI  - Surgical presentation and outcome of parotid gland tumours.
AB  - OBJECTIVE: To assess the clinical presentation and outcome of surgical management
      of various parotid gland disorders requiring parotidectomy. STUDY DESIGN: Case
      series. PLACE AND DURATION OF STUDY: Department of General Surgery, Pakistan
      Institute of Medical Sciences (PIMS), Islamabad, from January 2003 to December
      2010. METHODOLOGY: Patients presenting in surgical OPD with parotid gland
      disorders requiring parotidectomy were included. Data were obtained through the
      Hospital Management Information System (HMIS) and patient charts. The
      sociodemographic profile of the patient, presenting features among patients,
      benign versus malignant nature of the disease, FNAC reports, type of surgical
      procedure instituted, complications encountered and histology reports of the
      surgical specimens were all recorded on a proforma. The data were subjected to
      statistical analysis with SPSS version 15. RESULTS: Out of 126 patients, 62 (49%)
      were males and 64 (51%) females with mean age of 41 +/- 12.6 years. All had
      presented with a lump usually painless. One hundred and fourteen (90.47%)
      patients had benign pathology while 9.52% (n = 12) had malignanciy. Superficial
      parotidectomy was carried out in 79.36% (n = 100) patients, total parotidectomy
      in 19% (n = 24) and extended total parotidectomy was performed in 2 cases (with
      mucoepidermoid carcinoma). The most common post-operative complication was
      greater auricular nerve paresis (n = 19; 15%) followed by facial nerve transient
      paresis (n = 10; 8%). There was no in-hospital mortality. CONCLUSION: Parotid
      gland lumps commonly affect relatively young individuals of either gender. Most
      of the patients have benign pathology. Superficial parotidectomy is the most
      commonly offered surgical procedure. Parotid surgeries are safely performed in
      general surgery units with low morbidity and no mortality.

PMID- 24034186
TI  - Evaluation of different phenotypic methods for detection of amp C Beta-lactamase
      producing bacteria in clinical isolates.
AB  - OBJECTIVE: To compare the sensitivity and specificity of different phenotypic
      methods for detection of Amp C betalactamase producing bacteria. STUDY DESIGN:
      Analytical study. PLACE AND DURATION OF STUDY: Department of Microbiology, Army
      Medical College / National University of Sciences and Technology (NUST),
      Islamabad, Pakistan, from June 2010 to December 2010. METHODOLOGY: A total of 150
      clinical isolates were screened for presence of Amp C beta-lactamase by using the
      cefoxitin disc. The confirmatory methods evaluated were inhibitor based assay
      (boronic acid), Amp C disc test and Amp C Etest. Three dimensional enzyme extract
      assay was used as the reference method for determining the sensitivity and
      specificity. RESULTS: Among the total isolates tested, 62.8% bacteria showed the
      presence of Amp C beta-lactamase by standard three dimensional enzyme extract
      assay. Among the three methods compared, boronic acid disk test found out to be
      highly sensitive (88%) and specific (92%) for the detection of Amp C beta
      lactamase producing bacteria. CONCLUSION: Detection of Amp C production is
      crucial in order to establish the antibiotic therapy and to attain the favourable
      clinical outcomes. Implementation of simple tests like boronic acid disk tests in
      the laboratories will help to alleviate the spread of Amp C beta-lactamase
      harboring organisms.

PMID- 24034187
TI  - Comparison of sensitivity of QuantiFERON-TB gold test and tuberculin skin test in
      active pulmonary tuberculosis.
AB  - OBJECTIVE: To compare the sensitivity of tuberculin skin test (TST) and
      quantiFERON-TB gold test (QFT-G) in active pulmonary tuberculosis. STUDY DESIGN:
      Analytical study. PLACE AND DURATION OF STUDY: Department of Pulmonology, Fauji
      Foundation Hospital, Rawalpindi, from July 2011 to January 2012. METHODOLOGY:
      QuantiFERON-TB gold test (QFT-G) was evaluated and compared it with tuberculin
      skin test (TST) in 50 cases of active pulmonary tuberculosis, in whom tuberculous
      infection was suspected on clinical, radiological and microbiological grounds.
      Sensitivity was determined against postive growth for Mycobacterium tuberculosis.
      RESULTS: Out of 50 cases, 43 were females and 7 were males. The mean age was
      41.84 +/- 19.03 years. Sensitivity of QFT-G was 80% while that of TST was 28%.
      CONCLUSION: QFT-G has much higher sensitivity than TST for active pulmonary
      tuberculosis. It is unaffected by prior BCG administration and prior exposure to
      atypical mycobacteria. A positive QFT-G result can be an adjunct to diagnosis in
      patients having clinical and radiological data compatible with pulmonary
      tuberculosis.

PMID- 24034188
TI  - In vitro susceptibility of chloramphenicol against methicillin-resistant
      Staphylococcus aureus.
AB  - OBJECTIVE: To determine the in vitro susceptibility of chloramphenicol against
      methicillin-resistant Staphylococcus aureus. STUDY DESIGN: Cross-sectional study.
      PLACE AND DURATION OF STUDY: Department of Microbiology, Armed Forces Institute
      of Pathology, Rawalpindi, from January to June 2012. METHODOLOGY: One hundred and
      seventy four isolates of methicillin-resistant Staphylococcus aureus were
      included in this study using cefoxitin (30 MUg) disc for detection. Minimum
      inhibitory concentration (MIC) of chloramphenicol against MRSA was determined by
      using E-strip (AB BIO DISK). The susceptibility was determined by swabbing the
      Mueller-Hinton agar (MHA) plates with the resultant saline suspension of MRSA and
      applying E-strip of chloramphenicol from AB Biodisk Sweden and determining the
      MIC of chloramphenicol (in MUg/ml). Clinical and Laboratory Standards Institute
      (CLSI) recommendations of <= 8 MUg/ml being sensitive, 16 MUg/ml as intermediate
      and >=32 MUg/ml as resistant were followed in interpreting the results. RESULTS:
      Out of the 174 MRSA isolates, 132 (75.86%) isolates were susceptible to
      chloramphenicol with MICs of <= 8 MUg/ml, 38 (21.84%) were resistant >=32 MUg/ml
      while 4 (2.30%) were in intermediate range with MIC of 16MUg/ml. CONCLUSION:
      Chloramphenicol has shown good in vitro activity against MRSA and is likely to
      have a key role in the treatment of MRSA infections providing us a good
      alternative to newer expensive antimicrobials in resource limited countries.

PMID- 24034189
TI  - Long-term outcome of primary external dacryocystorhinostomy.
AB  - OBJECTIVE: To assess the long-term functional outcome of external
      dacryocystorhinostomy (DCR) in terms of epiphora. STUDY DESIGN: Single-group
      cohort study. PLACE AND DURATION OF STUDY: Section of Ophthalmology, The Aga Khan
      University Hospital, Karachi, from January 2000 to June 2010. METHODOLOGY: This
      study included adults who underwent external DCR surgery at the AKUH during
      January 2000 to June 2010. The main outcome measure was the proportion of
      patients reporting to have developed epiphora after surgery. During the
      telephonic interviews participants were asked if they had a recurrence (symptoms
      such as watering or discharge) after surgery. Individuals answering in
      affirmative were asked when the symptoms started. Data on age at surgery, gender
      and pre-operative symptoms were collected from medical records. Recurrence-free
      curves were calculated according to the Kaplan-Meier method. RESULTS: A total of
      44 persons who underwent DCR surgery were contactable by telephone in 2011 and
      all agreed to participate in the study. The mean age of the patients at the time
      of surgery was 48.0 +/- 15.8 years. Overall, 38.6% (17/44) participants reported
      having developed epiphora after surgery. The overall median recurrence-free time
      was 1.7 years; there was no statistically significant difference in the median
      recurrence-free time between men and women. CONCLUSION: The long-term functional
      outcome of external DCR surgery does not appear to be optimal and, in fact, far
      worse than the short-term results reported in the international literature.

PMID- 24034190
TI  - Mini transverse versus longitudinal incision in carpal tunnel syndrome.
AB  - OBJECTIVE: To evaluate the effectiveness of mini-transverse compared with mini
      longitudinal incision for carpal tunnel release (CTR) with reference to
      postoperative functional capacity, symptom severity and complication rate. STUDY
      DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Cumhuriyet University
      Medical Faculty, Department of Orthopaedics, Tokat State Hospital, Department of
      Orthopaedics and Medical Park Tokat Hospital, Department of Neurosurgery, from
      January 2007 to January 2009. METHODOLOGY: This study included 93 hands of 79
      patients with carpal tunnel syndrome (CTS), which were operated between 2007 and
      2009. Patients were divided according to incision types into Group-1 (undergoing
      mini-longitudinal incision) and Group-2 (undergoing mini-transverse incision).
      Patients were evaluated initially and at 3 weeks after treatment according to
      symptom severity and functional status of Boston Questionnaire (BQ). Demographic
      and clinical data were analyzed and compared statistically between two groups.
      RESULTS: Statistically significant differences were observed in BQ symptom and
      functional scores between the pre- and postoperative period (p < 0.0001). BQ
      symptom and functional scores at postoperative period were better in Group-1 than
      Group-2 (p = 0.044 and p = 0.023 respectively). The scar hypersensitivity (p =
      0.258) and tenderness (p = 1.00) associated with the incision sites were not
      statistically different. CONCLUSION: Longitudinal incision is more effective on
      symptom and functional conditions than transverse incision. However, there was
      less scar formation with transverse incision.

PMID- 24034191
TI  - Effect of ascorbic acid on long-term cold exposure induced changes in thyroid
      activity in Sprague Dawley rats.
AB  - OBJECTIVE: To determine the effect of ascorbic acid supplementation on long-term
      cold exposure induced changes in thyroid activity in Sprague-Dawley rats. STUDY
      DESIGN: Experimental study. PLACE AND DURATION OF STUDY: Physiology Department of
      Islamic International Medical College, Rawalpindi, National Institute of Health,
      Islamabad and Railway Hospital, Rawalpindi, from January to December 2009.
      METHODOLOGY: Ninety Sprague-Dawley rats were randomly divided into three groups
      of control, cold exposed and cold exposed along with ascorbic acid
      supplementation. After one month, their thyroid levels were analyzed by using
      chemiluminescent immunometric assay on Siemens Immulite 2000 Analyzer. RESULTS:
      After 4 weeks of cold exposure to experimental animals, the thyroid activity was
      raised significantly in the cold exposed group as compared to the control group
      (p-value for T3 difference = 0.004, T4 difference = 0.002 and TSH difference <
      0.001). Supplementation with ascorbic acid in the third group normalized the
      thyroid hormone activity with p-value for difference in levels of T3 being
      0.6661, T4 = 0.027 and TSH = 0.0028. CONCLUSION: Ascorbic acid prevented the cold
      induced changes in thyroid hormone levels in rodents.

PMID- 24034192
TI  - Small eyes big problems: is cataract surgery the best option for the
      nanophthalmic eyes?
AB  - Nanophthalmos refers to an eyeball of short axial length, usually less than 20 mm
      which leads to angle closure glaucoma due to relatively large lens. Intra-ocular
      lens extraction relieves the angle closure in nanophthalmos. Cataract surgery in
      a nanophthalmic eye is technically difficult with high risk of complications such
      as posterior capsular rupture, uveal effusion, choroidal haemorrhage, vitreous
      haemorrhage, malignant glaucoma, retinal detachment and aqueous misdirection.
      Various options are explained in the literature to perform cataract surgery in
      nanophthalmos, like extracapsular cataract extraction with or without
      sclerostomy; small-incision cataract extraction by phacoemulsification which not
      only helps maintain the anterior chamber during surgery but also reduces the
      incidence of complications due to less fluctuation of intraocular pressure (IOP)
      during the surgery. Cataract surgery deepens and widens the anterior chamber
      angle in nanophthalmic eyes and has beneficial effects on IOP in eyes with
      nanophthalmos but is associated with a high incidence of complications. 

PMID- 24034194
TI  - Ortner syndrome with recurrent pericardial effusion: a diagnostic and therapeutic
      dilemma.
AB  - Ortner syndrome is a rare condition characterized by hoarseness of voice in
      association with a cardiovascular disease. It is caused by compression of the
      left recurrent laryngeal nerve by the pulmonary artery or left atrium. Mitral
      stenosis is a well-recognized cause, however, a number of cardiac and non-cardiac
      conditions have also been described. Prognosis of Ortner syndrome depends on the
      underlying aetiology as well as the duration of illness. The case presented here
      describes a 35-year-old man with hoarseness of voice with recurrent pericardial
      effusion. Initially, a microbiologically proven diagnosis of tuberculous
      aetiology with resistance to Rifampicin was made; lack of optimum response and
      recurrence of pericardial effusion lead to subsequent diagnosis of metastatic
      adenocarcinoma. The patient responded to some extent to systemic and
      intrapericardial chemotherapy. Immunocompromised state associated with malignancy
      may predispose to infection including tuberculosis.

PMID- 24034193
TI  - Retained temporary epicardial pacing wires: a rare cause of prosthetic valve
      endocarditis.
AB  - Temporary epicardial pacing wires (TEPWs) are commonly used during cardiac
      surgery to meet unforeseen complications like heart blocks or asystole. These are
      generally considered to be safe. The incidence of major complications with their
      use is low, but could be life threatening. Complications can be divided into
      those encountered during placement, removal, or retention of temporary epicardial
      pacing wires. We report a rare case of prosthetic mitral valve endocarditis
      caused by TEPWs that migrated into the pulmonary artery, presenting 5 months
      following mitral and aortic valve replacement surgery that required percutaneous
      removal of these temporary pacing wires via a right femoral vein approach. This
      case highlights the fact that delayed complications can rarely occur due to
      retained TEPWs and may have serious consequences. This fact should be taken into
      account when the strategy on dealing with such wires following cardiac surgery is
      determined. Routine retention of temporary epicardial pacing wires is not
      recommended. 

PMID- 24034195
TI  - Adrenal angiomyolipoma.
AB  - Adrenal angiomyolipoma is a rare tumour arising from the mesenchymal tissue
      containing fat cells. A 72 years old lady presented with right upper quadrant
      pain. She underwent laparotomy after relevant imaging and investigations and was
      found to have a right sided adrenal angiomyolipoma confirmed on histopathology,
      which was encasing the inferior vena cava and renal veins. Due to its diagnostic
      difficulty, potential to achieve large size and possible complications; surgeons
      and pathologists should keep angiomyolipoma in mind when dealing with an adrenal
      mass. 

PMID- 24034196
TI  - Appendicitis in a malrotated gut: an unusual cause of left upper quadrant
      abdominal pain.
AB  - In this case report, we present a case of young male with left sided acute
      appendicitis who presented with left upper quadrant abdominal pain. The purpose
      of this report is to increase awareness in the emergency physicians and young
      surgeons of this rare presentation, with high suspicion of index could lead to
      facilitate early recognition and decrease morbidity and mortality. 

PMID- 24034197
TI  - An isolated tuberculous liver abscess in a non-immunocompromised patient.
AB  - A liver abscess is an uncommon extra-pulmonary manifestation of a common disease
      that is tuberculosis. It usually follows primary infection in the lung or the
      gut. Tuberculous liver abscess in a non-immunocompromised patient in the absence
      of primary disease elsewhere is an extremely rare occurrence. We report here a
      case of a tuberculous liver abscess in a 30 years old female who presented a
      considerable diagnostic challenge. 

PMID- 24034198
TI  - Mandibular ameloblastic carcinoma.
AB  - Ameloblastic carcinoma is a rare aggressive odontogenic tumour that exhibits
      malignant histologic features in the primary site or in metastasis. This rare
      tumour needs immediate attention because of its aggressive and infiltrative
      nature. However, there are controversies regarding the definitive treatment
      because of the very few cases in the literature database. Here, we report a case
      of a 64-year-old male Asian patient who presented with a non-tender exophytic
      proliferative mass of 3 months duration. It was finally diagnosed as ameloblastic
      carcinoma and promptly treated surgically with a regular follow-up. Local long
      term control and follow-up is imperative in such patient laying emphasis on
      potential pulmonary metastasis. 

PMID- 24034199
TI  - Epiglottic abscess causing acute airway obstruction in an adult.
AB  - Acute epiglottitis is an acute inflammation in the supraglottic region of the
      oropharynx which is a potentially life-threatening condition leading to rapid
      upper airway obstruction. An infrequent sequel of acute epiglottitis is the
      epiglottic abscess. Less than 50 cases have been reported in the international
      literature and even less are the cases that acute surgical intervention was
      necessary to secure the airway. We report a young man with sudden onset of
      odynophagia, dysphonia and dyspnea and rapidly progression of upper airway
      obstruction. Clinical examination with fiberoptic nasopharyngolaryngoscope in
      emergency department demonstrated an epiglottic abscess. An urgent tracheostomy
      was performed in order to secure patient's airway and afterward, the patient
      underwent direct laryngoscopy and drainage of abscess and intravenous antibiotics
      were administrated. The diagnosis of epiglottic abscess should be considered in
      adult patients with odynophagia and dysphonia. Principles of treatment include
      aggressive airway management, surgical drainage of abscess and intravenous
      antibiotics. 

PMID- 24034200
TI  - Pulmonary arteriovenous malformation in cryptogenic liver cirrhosis.
AB  - The cause in 10 - 20% cases of liver cirrhosis (LC) cannot be elucidated, and are
      thus termed cryptogenic. Pulmonary arteriovenous malformations (PAVMs) are
      relatively rare, but the most common anomaly involving the pulmonary tree.
      Although the rare correlation between LC and PAVM is well-known, there have been
      no reports of PAVMs occurring in cryptogenic LC. We report a case of PAVM that
      occurred in cryptogenic liver cirrhosis in a 3 years old male child. The child
      presented with complaints of malena, hematemesis and variceal bleed. The
      examination revealed a child with respiratory distress, irritability,
      tachycardia, clubbing and abdominal distention. He was worked up for recurrent
      variceal bleeding secondary to portal hypertension but the oxygen saturation
      during hospital stay kept deteriorating. The diagnosis of hepatopulmonary
      syndrome as the cause of persistent hypoxemia in the absence of other cardio
      pulmonary causes was then made by enhanced echocardiogram using agitated saline.
      He improved significantly after liver transplantation performed abroad. At a 6
      months follow-up, the child was stable with no evidence of intrapulmonary
      shunting on repeat echo. 

PMID- 24034201
TI  - A simple working classification proposed for the latrogenic lesions of teeth and
      associated structures in the oral cavity.
AB  - Iatrogenic lesions can affect both hard and soft tissues in the oral cavity,
      induced by the dentist's activity, manner or therapy. There is no approved simple
      working classification for the iatrogenic lesions of teeth and associated
      structures in the oral cavity in the literature. A simple working classification
      is proposed here for iatrogenic lesions of teeth and associated structures in the
      oral cavity based on its relation with dental specialities. The dental
      specialities considered in this classification are conservative dentistry and
      endodontics, orthodontics, oral and maxillofacial surgery and prosthodontics.
      This classification will be useful for the dental clinician who is dealing with
      diseases of oral cavity. 

PMID- 24034202
TI  - Frequently isolated bacteria and their culture and sensitivity pattern in a
      medical ICU.
AB  - Empirical antibiotic therapy in seriously ill patients requires careful selection
      of antibiotics. This study was planned to determine the pattern of bacterial
      infections and culture sensitivities in patients admitted to a medical intensive
      care unit (ICU). Patients with positive bacterial cultures from specimens of
      blood, urine, endo-tracheal tube, suction catheter, and tracheal aspirates were
      included. Data regarding microbial isolates and their culture sensitivities was
      collected. Escherichia coli (E. coli), Pseudomonas aerogenosa (PA), Klebsiella
      pneumonea (KP), Staphylococcus aureus (SA) and methicillin resistant
      Staphylococcus aureus (MRSA) were the most frequently isolated bacteria. E coli
      showed 100% sensitivity to sulbactam potentiated sulfoperazone, and meropenam. PA
      were sensitive to gentamycin, imepenam, and sparfloxacin in > 70% cases. All KP
      isolates were sensitive to amikacin, imepenam and sparfloxacin. SA were 100%
      sensitive to amikacin. MRSA were 100% sensitive to vancomycine and linezolid.
      Based on these results, sulbactam potentiated cefoperazone in combination with
      amikacin seems the best empirical antibiotic regimen. Imipenam usage can be an
      alternative. 

PMID- 24034203
TI  - Use of enteral nutritional supplementation: a survey of level II and III neonatal
      units in England.
AB  - Enteral nutritional supplementation is widely used in preterm babies on Neonatal
      Units (NNUs). There is little published evidence on appraising their long-term
      efficacy. We evaluated the current practice of enteral nutritional
      supplementation in 96 level II and III NNUs in England. 96%, 98%, 98% and 56%
      units use breast milk fortification (BMF), iron, multivitamins and folic acid
      supplementation respectively. Iron, multivitamins and folic acid supplements are
      routinely commenced in babies < 35 weeks gestation by 73%, 68% and 39% NNUs
      respectively. Seventy eight percent NNUs only use BMF for babies that are not
      gaining weight. Continuing variable practice of enteral nutritional
      supplementation and current use of anecdotal evidence and best guess
      recommendations highlights the need for a unified approach and collaborative
      multinational research to produce standardised guidelines. 

PMID- 24034204
TI  - Cardiothoracic surgery: a dying specialty in the modern medical era.

PMID- 24034205
TI  - Congenital nephrotic syndrome with hypothyroidism: an unusual association.

PMID- 24034206
TI  - Clinical patterns of juvenile idiopathic arthritis in Zambia.
AB  - BACKGROUND: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of
      disorders with different disease manifestations among various populations. There
      are few reports of JIA among indigenous Africans especially sub-Saharan Africa.
      We present herein the clinical patterns of JIA encountered at a tertiary hospital
      in Lusaka, Zambia. METHOD: Hospital records of patients with a diagnosis of
      chronic arthritis with onset at the age of 16 years or less presenting to
      University Teaching Hospital, Lusaka, Zambia for the periods 1994-98 and 2006
      2010 were retrospectively reviewed and reclassified as Juvenile Idiopathic
      Arthritis (JIA) based on the International League of Associations for
      Rheumatology (ILA R) JIA diagnostic criteria. RESULTS: In total, 126 patients
      with chronic arthritis of onset at age 16 years or less were evaluated over these
      periods at the hospital. Of these, 85 could further be analyzed by ILAR JIA
      criteria but 7 (8.24%) were HIV seropositive and were assessed separately. The
      average age at disease onset among the 78 JIA patients was 8.70 years (range: 1
      15 years) with average age at first visit to hospital being 11.3 years (range: 2
      to 25 years) and with a female to male ratio of 1.2:1. Polyarticular rheumatoid
      factor negative JIA, at 34.62%, was the most frequent type of chronic arthritis
      encountered. Oligoarthritis was found in 32.05% while 11.54% and 14.10% were
      polyarticular rheumatoid factor positive and systemic JIA, respectively.
      Enthesitis-related arthritis was found in 6.41% and only 1.28% were determined to
      have psoriatic arthritis among this population. CONCLUSION: JIA is predominantly
      a polyarticular rheumatoid factor negative disease in Zambia. Late presentation
      is an issue with major implications for educational input and resource
      acquisition. There is need to elucidate the genetics and environmental factors of
      JIA in this region.

PMID- 24034207
TI  - Anterior translocation of the right pulmonary artery to avoid airway compression
      in aortic arch repair.
AB  - BACKGROUND: Airway compression caused by an enlarged right pulmonary artery (RPA)
      in patients with a large shunt can usually be managed with intracardiac repair
      and concomitant anterior aortopexy. However, anterior aortopexy can be less
      effective or even dangerous in patients with coexisting arch anomaly due to
      excessive tension at the arch repair site. We have adopted anterior translocation
      of RPA without aortic transection in the group of patients with a high risk of
      postoperative airway compression. We reviewed the early and midterm results of
      this technique. METHODS: From February 2006 to January 2013, 8 patients underwent
      RPA anterior translocation as a concomitant procedure in one-stage repair of
      ventricular septal defect (VSD) and aortic arch anomaly to avoid postoperative
      airway problems. The enlarged RPA was disconnected from the main pulmonary artery
      (MPA) at its origin and was relocated anterior to the ascending aorta, and
      subsequently reimplanted to the U-shaped trapdoor incision at the anterolateral
      MPA wall. The mean age at operation was 34 days (median, 14 days, 6 to 77 days),
      and the mean body weight was 3.6 kg (2.15 to 5.5 kg). All patients had
      coarctation of the aorta and VSD except 1 who had aortic arch interruption. Five
      patients were dependent on a ventilator preoperatively. Six patients had evidence
      of preoperative bronchial compression (left; 4, right and left; 2), and 2 had a
      high probability of postoperative bronchial compression due to unusual anterior
      location of the descending aorta. RESULTS: There was no early or late death.
      There were no postoperative airway problems such as reintubation or left lung
      atelectasis. Widely patent RPA was confirmed on postoperative computed
      tomographic angiography in all patients. The mean follow-up duration was 54.0 +/-
      17.1 months. One patient required balloon angioplasty for mild stenosis at the
      clamping site 3 years after the operation. All patients had no RPA stenosis at
      the latest follow-up evaluation. CONCLUSIONS: Anterior translocation of the RPA
      as a concomitant procedure in one-stage repair of VSD and arch anomaly is a safe
      and effective procedure to avoid postoperative airway problems in high-risk
      patients.

PMID- 24034209
TI  - Rare earth metals are essential for methanotrophic life in volcanic mudpots.
AB  - Growth of Methylacidiphilum fumariolicum SolV, an extremely acidophilic
      methanotrophic microbe isolated from an Italian volcanic mudpot, is shown to be
      strictly dependent on the presence of lanthanides, a group of rare earth elements
      (REEs) such as lanthanum (Ln), cerium (Ce), praseodymium (Pr) and neodymium (Nd).
      After fractionation of the bacterial cells and crystallization of the methanol
      dehydrogenase (MDH), it was shown that lanthanides were essential as cofactor in
      a homodimeric MDH comparable with one of the MDHs of Methylobacterium extorquens
      AM1. We hypothesize that the lanthanides provide superior catalytic properties to
      pyrroloquinoline quinone (PQQ)-dependent MDH, which is a key enzyme for both
      methanotrophs and methylotrophs. Thus far, all isolated MxaF-type MDHs contain
      calcium as a catalytic cofactor. The gene encoding the MDH of strain SolV was
      identified to be a xoxF-ortholog, phylogenetically closely related to mxaF.
      Analysis of the protein structure and alignment of amino acids showed potential
      REE-binding motifs in XoxF enzymes of many methylotrophs, suggesting that these
      may also be lanthanide-dependent MDHs. Our findings will have major environmental
      implications as metagenome studies showed (lanthanide-containing) XoxF-type MDH
      is much more prominent in nature than MxaF-type enzymes.

PMID- 24034210
TI  - Benchmarking outcomes in resident-performed cataract surgery with toric
      intraocular lenses: response.

PMID- 24034208
TI  - Reducing infection transmission in solid organ transplantation through donor
      nucleic acid testing: a cost-effectiveness analysis.
AB  - For solid organ transplant (SOT) donors, nucleic acid-amplification testing (NAT)
      may reduce human immunodeficiency virus (HIV) and hepatitis C virus (HCV)
      transmission over antibody (Ab) testing given its shorter detection window
      period. We compared SOT donor NAT + Ab versus Ab alone using decision models to
      estimate incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted
      life year [QALY] gained) from the societal perspective across a range of HIV/HCV
      prevalence values and NAT costs. The cost per QALY gained was calculated for two
      scenarios: (1) favorable: low cost ($150/donor)/high prevalence (HIV: 1.5%; HCV:
      18.2%) and (2) unfavorable: high cost ($500/donor)/low prevalence (HIV: 0.1%;
      HCV: 1.5%). In the favorable scenario, adding NAT screening cost $161 013 per
      QALY gained for HIV was less costly) for HCV, and cost $86 653 per QALY gained
      for HIV/HCV combined. For the unfavorable scenario, the costs were $15 568 484,
      $221 006 and $10 077 599 per QALY gained, respectively. Universal HCV NAT + Ab
      for donors appears cost-effective to reduce infection transmission from SOT
      donors, while HIV NAT + Ab is not, except where HIV NAT is <=$150/donor and
      prevalence is >=1.5%. Our analyses provide important data to facilitate the
      decision to implement HIV and HCV NAT for deceased SOT donors and shape national
      policy regarding how to reduce infection transmission in SOT.

PMID- 24034211
TI  - Lack of association between family history of stroke and 1-year outcomes after
      acute ischemic stroke in Chinese.

PMID- 24034212
TI  - Using corrected cone-beam CT image for accelerated partial breast irradiation
      treatment dose verification: the preliminary experience.
AB  - BACKGROUND: Accurate target localization is mandatory in the accelerated partial
      breast irradiation (APBI) delivery. Dosimetric verification for positional error
      will further guarantee the accuracy of treatment delivery. The purpose of this
      study is to evaluate the clinical feasibility of a cone beam computer tomographic
      (CBCT) image correction method in APBI. METHODS: A CBCT image correction method
      was developed. First, rigid image registration was proceeded for CTs and CBCTs;
      second, these images were separated into four parts; then, ratio images for each
      of the four parts of planning CTs/CBCTs were calculated and filtered to reduce
      the high spatial frequency; finally, the enhanced CBCT images were generated
      combing the four parts. An anthropomorphic thorax rando phantom was used to
      evaluate the feasibility and accuracy of the CBCT correction method. The CBCT
      images of consecutive 10 patients receiving APBI were corrected using the above
      method and dosimetric variations were evaluated. Each set of CBCT is composed of
      three images: one acquired after skin-marker setup, one after online setup
      correction and one after treatment delivery. RESULTS: The phantom study showed
      the improved accuracy of dose calculation with corrected CBCT. The Dose Volume
      Histogram (DVH) difference between the planning CT and corrected CBCT is less
      than the difference between the planning CT and original CBCT. The maximum dose
      difference between the corrected CBCT and planning CT is 0.8% in PTV_EVAL V100,
      which is 3.8% between original CBCT and planning. In the patient study, 67.4% of
      fractions benefit from CBCT setup corrections in PTV_EVAL D95, while in 47.4% of
      the fractions, reduced dose coverage was found on the post-treatment CBCT.
      Overall, the CBCT based initial setup correction guaranteed target dose coverage
      in 9 patients. CONCLUSIONS: A generic CBCT image correction algorithm was created
      and proved to be easily implemented in clinic. Compared to the original CBCT, the
      corrected CBCT has more accuracy in dose calculation. The CBCT guided APBI based
      on initial skin setup is not sufficient to guarantee the accurate dose delivery
      throughout each fraction. The long treatment delivery time may compromise the
      target coverage benefits in some patients.

PMID- 24034213
TI  - Epstein-Barr virus-associated smooth muscle tumors in a composite tissue
      allograft and a pediatric liver transplant recipient.
AB  - Epstein-Barr virus (EBV) is known to establish latent infections in B-lymphocytes
      that can cause lymphoproliferative disorders particularly in immunocompromised
      patients. More recently, the development of rare EBV-associated smooth muscle
      tumors has been reported in transplant recipients. We herein describe 2 new cases
      of EBV-associated post-transplant smooth muscle tumors (EBV-PTSMT), including the
      first in a facial composite tissue graft recipient. Among the striking features
      shared by these 2 patients were their young ages, the fact that they were naive
      for EBV before the transplantation, that they developed a post-transplant
      lymphoproliferative disorder before the diagnosis of EBV-PTSMT, and that they
      responded favorably to reduction of immunosuppression. Radiological and
      histologic features of EBV-PTSMT are shown. Finally, pathophysiology and
      therapeutic management of EBV-PTSMT are discussed based on a comprehensive review
      of the literature. 

PMID- 24034214
TI  - Alternatives to antibiotics as growth promoters for use in swine production: a
      review.
AB  - In the past two decades, an intensive amount of research has been focused on the
      development of alternatives to antibiotics to maintain swine health and
      performance. The most widely researched alternatives include probiotics,
      prebiotics, acidifiers, plant extracts and neutraceuticals such as copper and
      zinc. Since these additives have been more than adequately covered in previous
      reviews, the focus of this review will be on less traditional alternatives. The
      potential of antimicrobial peptides, clay minerals, egg yolk antibodies,
      essential oils, eucalyptus oil-medium chain fatty acids, rare earth elements and
      recombinant enzymes are discussed. Based on a thorough review of the literature,
      it is evident that a long and growing list of compounds exist which have been
      tested for their ability to replace antibiotics as feed additives in diets fed to
      swine. Unfortunately, the vast majority of these compounds produce inconsistent
      results and rarely equal antibiotics in their effectiveness. Therefore, it would
      appear that research is still needed in this area and that the perfect
      alternative to antibiotics does not yet exist. 

PMID- 24034215
TI  - Phononics - a field that has come of age.

PMID- 24034216
TI  - Fabrication of lactate biosensor based on lactate dehydrogenase immobilized on
      cerium oxide nanoparticles.
AB  - An electrochemical biosensor was developed to determine lactate that plays an
      important role in clinical diagnosis, fermentation and food quality analysis.
      Abnormal concentration of lactate has been related to diseases such as hypoxia,
      acute heart disorders, lactic acidosis, muscle fatigue and meningitis. Also,
      lactate concentration in blood helps to evaluate the athletic performance in
      sports. The main aim of the work is to fabricate NADH/LDH/Nano-CeO2/GCE bio
      electrode for sensing lactate in human blood samples. Toward this, CeO2
      nanoparticles were synthesized by a hydroxide mediated approach using cerium
      nitrate hexahydrate (Ce(NO3)3.6H2O) and NaOH as precursors. X-ray diffraction
      (XRD) and Field Emission Scanning Electron Microscopy (FE-SEM) studies were
      carried out to determine the structural and morphological characteristics of CeO2
      nanoparticles. XRD pattern indicated the formation of highly crystalline CeO2
      nanoparticles with face centered cubic structure. The FE-SEM studies revealed the
      formation of nanospherical particles of size 29.73+/-2.59 nm. The working
      electrode was fabricated by immobilizing nicotinamide adenine dinucleotide (NADH)
      and lactate dehydrogenase (LDH) on GCE surface with CeO2 nanoparticles as an
      interface. Electrochemical studies were carried out through cyclic voltammetry
      using a three electrode system with NADH/LDH/NanoCeO2/GCE as a working electrode,
      Ag/AgCl saturated with 0.1M KCl as a reference electrode and Pt wire as a counter
      electrode. From the amperometric study, the linearity was found to be in the
      range of 0.2-2 mM with the response time of less than 4s.

PMID- 24034217
TI  - High-yield aqueous phase exfoliation of graphene for facile nanocomposite
      synthesis via emulsion polymerization.
AB  - Aqueous phase exfoliation was developed for producing high-yield graphene
      nanosheets from expanded graphite (EG). The process included ultrasonication with
      sodium dodecyl sulfate (SDS) emulsion in aqueous phase. The high throughput
      exfoliation process was characterized by UV-vis spectroscopy, transmission
      electron microscopy (TEM) and electrical impedance spectroscopy (EIS). Controlled
      sonication experiments revealed that optimum exfoliation corresponds to maxima in
      UV-vis spectra. TEM results showed that the exfoliated graphene comprised
      nanoflakes having <=5 layers (~60%) and <=10 layers for 90% of the product. The
      potential use of this highly dispersed graphene was demonstrated by one-pot
      synthesis of graphene/polymer composite via in situ emulsion polymerization with
      styrene. The integrated role of SDS included adsorption and exfoliation of
      graphite, dispersion of graphene produced and assisting with micelle formation in
      emulsion. The high surface area graphene nanosheets as dispersed phase in
      polymeric nanocomposites showed significant improvement in thermal stability and
      electrical conductivity.

PMID- 24034218
TI  - Heterogeneous Fenton-like oxidation of monochlorobenzene using green synthesis of
      iron nanoparticles.
AB  - Iron nanoparticles (Fe NPs) were synthesized using tea extracts as a catalyst for
      the Fenton-like oxidation of monochlorobenzene (MCB), where 69%, 53%, and 39% of
      MCB were, respectively, degraded by Fe NPs synthesized using green tea extracts,
      oolong tea extracts, and black tea extracts. Fe NPs synthesized using green tea
      extracts (GT-Fe NPs) demonstrated the best degradation since green tea contains a
      high concentration of caffeine/polyphenols used as both reducing and capping
      agents in the synthesis of Fe NPs. This was confirmed by SEM image, EDS, and XRD
      pattern of GT-Fe NPs. In addition, batch experiments show that the oxidation of
      MCB and the removal of chemical oxygen demand (COD) using GT-Fe NPs were 81% and
      31%, respectively, at optimal conditions, where dosages were 0.6g/L GT-Fe NPs,
      0.045 mol/L H2O2, and initial pH of 3.0. Compared to homogeneous Fenton oxidation
      of MCB, GT-Fe NPs as a heterogeneous catalyst indicate that Fe(2+) and Fe(3+)
      leached from GT-Fe NPs nanoparticles and consequently reduced the formation of
      iron sludge. Finally, GT-Fe NPs were successful in removing MCB from wastewaters,
      and the possible Fenton-like oxidative mechanism of MCB was proposed. The
      proposition was based on adsorption of MCB on the surface of GT-Fe NPs,
      decomposition of H2O2, generation of hydroxyl radicals, and oxidation of MCB.

PMID- 24034219
TI  - Induced-charge electroosmotic flow around dielectric particles in uniform
      electric field.
AB  - The current research of induced-charge electroosmotic flow (ICEOF) is mostly
      confined to systems with ideally or fully polarizable surfaces (e.g., metal).
      However, most materials in nature have various degrees of polarizability, which
      directly affects the induced charges and subsequently the induced-charge
      electroosmotic flow. This paper studied the effect of the polarizability of the
      materials on the ICEOF. An analytical expression of the induced potential on the
      surface of a dielectric particle in a uniform electrical field was derived. Three
      dimensional transient numerical simulations of the ICEOF and the motion of
      dielectric particles were performed to study the effect of the polarizability.
      Simulation results show that the transportation of the dielectric particle in a
      microchannel is not affected by the polarizability of the particle; however, the
      interaction of two dielectric particles is sensitive to the polarizability of the
      particles. 

PMID- 24034220
TI  - Specific behavior of the p-aminothiophenol--silver sol system in their Ultra
      Violet-Visible (UV-Visible) and Surface Enhanced Raman (SERS) spectra.
AB  - The UV-Visible and Surface Enhanced Raman Spectroscopy (SERS) behavior of silver
      sol (a typical SERS agent) were studied in the presence of different bifunctional
      thiols such as p-aminothiophenol, p-mercaptobenzoic acid, p-nitrothiophenol, p
      aminothiophenol hydrochloride, and 2-mercaptoethylamine hydrochloride in diluted
      aqueous solution. Our results confirm that the p-aminothiophenol induced
      aggregation of citrate stabilized silver colloid originates from its
      electrostatic nature, as well as the azo-bridge formation cannot be the reason of
      the observed time dependent UV-Visible spectra. Based on our parallel SERS and
      electrospray ionization mass spectrometry measurements, we have concluded that
      certain amount of oxidized form of the probe molecule has to be present for the
      so-called b2-mode enhancement in the SERS spectrum of p-aminothiophenol. Our
      findings seem to support the idea that the azo-bridge formation is responsible
      for the b2-mode enhancement in the SERS spectrum of p-aminothiophenol. 

PMID- 24034221
TI  - Electrokinetics in undeveloped flows.
AB  - For the correct interpretation of results of tangential electrokinetic
      measurements with porous materials, in particular, composite/asymmetric membranes
      on porous supports, it is necessary to have the data available for various
      channel heights. In some kinds of equipment, the variation of channel height is
      technically possible only for a range of relatively large heights. This
      communication shows that under these conditions, the fluid flow can become
      undeveloped and the conventional approaches to the interpretation of
      electrokinetic measurements should be modified accordingly. In particular, the
      dependence of streaming-current coefficient on the channel height becomes sub
      linear. If the experimental data are available only for larger channel heights,
      this can be mistakenly taken for the manifestation of contribution of porous sub
      structure to the streaming current. In this communication, we investigate
      electrokinetic phenomena in undeveloped flows both numerically and
      experimentally. We confirm that the aforementioned sub-linearity occurs for
      nonporous as well as porous substrates. We also demonstrate that the channel
      heights estimated from the volume flow rate by using numerical simulations of
      undeveloped flows are in very good agreement with the reference values obtained
      from the electrical conductance (in contrast to the values estimated by using the
      conventional approach of Hagen-Poiseuille equation). The numerical fitting of
      channel-height dependences of streaming-current coefficient enables us to
      separate the contributions of external surface and porous sub-structure (in case
      of porous substrates) and obtain quite reasonable values of (effective) zeta
      potentials in both cases. Nonetheless, the accuracy of experimental data
      deteriorates with increasing channel height, so it is generally advisable to vary
      the heights within a range below 100-150 MUm.

PMID- 24034222
TI  - Transformation of micelles into supramolecular vesicles triggered by the
      formation of [4]pseudorotaxanes.
AB  - Spontaneous formation of supramolecular vesicles which are triggered by the
      formation of [4]pseudorotaxane B was demonstrated, whereas both Guest and
      [2]pseudorotaxane A, the precursors of [4]pseudorotaxane B, only assemble into
      micelles in DMF/water solution. The remarkable transformation of Guest from
      micelles to supramolecular vesicles was confirmed through DLS, TEM, and Cryo-TEM
      experiments. The cumulative release of a model drug, 5-carboxyfluorescein (CF),
      was used to determine the permeability of the supramolecular vesicles. No leakage
      of entrapped CF was observed within 48 h by fluorescence measurement, indicating
      the high stability of supramolecular vesicles. The formation mechanism of
      supramolecular vesicles self-assembled by [4]pseudorotaxane B was also discussed.
      In [4]pseudorotaxane B, CB[6] is used to increase the hydrophobic property of
      site beta, which acts as hydrophobic "tail." Meanwhile, CB[7] plays the role of
      increasing "head area" of site alpha, which acts as hydrophilic "head." The
      synergistic effect of CB[6] and CB[7] induces the formation of supramolecular
      vesicles. Moreover, the effect of DMF content was investigated by TEM
      observations. It was found that the [4]pseudorotaxane B can self-assemble into
      regular supramolecular vesicles when the DMF content is in the range of 50-70%.

PMID- 24034223
TI  - Comparison of complexes formed by a crustacean and a vertebrate trypsin with
      bovine pancreatic trypsin inhibitor - the key to achieving extreme stability?
AB  - This paper provides evidence for the extremely high resistance of a complex of
      crayfish trypsin (CFT) and bovine pancreatic trypsin inhibitor (BPTI) against
      heating and chemical denaturing agents such as sodium dodecyl sulfate (SDS) and
      urea. To dissociate this complex, 15 min boiling in SDS was necessary, compared
      to a complex of bovine trypsin (BT) (EC 3.4.21.4) and BPTI, which dissociates in
      SDS without boiling. The CFT-BPTI complex remained stable even in 9 m urea, while
      the BT-BPTI complex started to dissociate at concentrations of approximately 4 m
      urea. The melting temperatures of the BT-BPTI and CFT-BPTI complexes, as
      determined by differential scanning calorimetry, were found to be 79.6 and 100.1 
      degrees C, respectively. The behaviour of the apo-enzymes - CFT was found to have
      a less stable structure compared to BT - did not provide a definite indication
      regarding the differential effects on their stabilities. To explore the
      structural features responsible for this extreme stability, we crystallized CFT
      in complex with BPTI, and identified extended contacts compared to the BT-BPTI
      complex. Comparison of the B-factors of similar trypsin-trypsin inhibitor
      complexes suggests that molecular flexibility of the components is also required
      for the strong protein-protein interaction. Although the structural reason for
      the extreme stability of the CFT-BPTI complex is not yet fully understood, our
      study may be a starting point for the development of new protein complexes with
      enhanced stability.

PMID- 24034224
TI  - Gene expression profile is associated with chemoradiation resistance in rectal
      cancer.
AB  - AIM: Patients with rectal cancer who achieve a complete pathological response
      after preoperative chemoradiation (CRT) have an improved oncological outcome.
      Identifying factors associated with a lack of response could help our
      understanding of the underlying biology of treatment resistance. This study aimed
      to develop a gene expression signature for CRT-resistant rectal cancer using high
      throughput nucleotide microarrays. METHOD: Pretreatment biopsies of rectal
      adenocarcinomas were prospectively collected and freshly frozen according to an
      institutional review board-approved protocol. Total tumour mRNA was extracted and
      gene expression levels were measured using microarrays. Patients underwent
      proctectomy after completing standard long-course CRT and the resected specimens
      were graded for treatment response. Gene expression profiles for nonresponders
      were compared with those of responders. Differentially expressed genes were
      analyzed for functional significance using the Ingenuity Pathway Analysis (IPA)
      software. RESULTS: Thirty-three patients treated between 2006 and 2009 were
      included. We derived 812-gene and 183-gene signatures separating nonresponders
      from responders. The classifiers were able to identify nonresponders with a
      sensitivity and specificity of 100% using the 812-gene signature, and sensitivity
      and specificity of 33% and 100% using the 183-gene signature. IPA canonical
      pathway analysis revealed a significant ratio of differentially expressed genes
      in the 'DNA double-strand break repair by homologous recombination' pathway.
      CONCLUSION: Certain rectal cancer gene profiles are associated with poor response
      to CRT. Alterations in the DNA double-strand break repair pathway could
      contribute to treatment resistance and provides an opportunity for further
      studies.

PMID- 24034225
TI  - Automated screening for tuberculosis by multiparametric analysis of data obtained
      during routine complete blood count.
AB  - INTRODUCTION: The main goal of this study was to develop a multiparametric cell
      population data (CPD) model that combines information from several morphologic
      parameters generated by DxH800, in addition to the traditional parameters
      regularly reported in the CBC-diff, and to test the performance of this model in
      screening the general population for primary tuberculosis (TB). METHODS: A total
      of 3741 study cases were divided into two groups, test and validation set at cut
      off value of 6000 WBCs/MUL. We developed multiparametric model for primary TB
      screening (TB hemeprint), selected CPD, and calculated parameters which could
      discriminate primary TB from other non-TB diseases and normal control in test
      set. We applied it to the validation set, which was a set of completely different
      samples, to test its reproducibility if applied to a routine laboratory test.
      RESULTS: After screening primary TB using TB hemeprint, sensitivity, specificity,
      PPV, and NPV were 85.4%, 89.6%, 31.1%, and 99.1%, respectively, in primary TB
      with lower than 6000 WBCs/MUL of test set (test set-L). In primary TB with higher
      than 6000 WBCs/MUL of test set (test set-H), those values were 83.1%, 85.6%,
      29.7%, and 98.6%, respectively. There were only 0.4% (2/461) and 0.6% (2/326) of
      normal control samples included in test set-L and -H, respectively. Diagnostic
      efficiencies except sensitivity in each validation set were very comparable with
      those in each test set. CONCLUSION: Tuberculosis hemeprint may allow us to screen
      primary TB with acceptable sensitivity and specificity using combination of TB
      specific CPD and calculated parameters.

PMID- 24034226
TI  - Determination of platinum surface contamination in veterinary and human oncology
      centres using inductively coupled plasma mass spectrometry.
AB  - The objective of this study was to determine the surface contamination with
      platinum-containing antineoplastic drugs in veterinary and human oncology
      centres. Inductively coupled plasma mass spectrometry was used to measure
      platinum levels in surface samples. In veterinary and human oncology centres,
      46.3 and 68.9% of the sampled surfaces demonstrated platinum contamination,
      respectively. Highest platinum levels were found in the preparation rooms (44.6
      pg cm(-2)) in veterinary centres, while maximal levels in human centres were
      found in oncology patient-only toilets (725 pg cm(-2)). Transference of platinum
      by workers outside areas where antineoplastic drugs were handled was observed in
      veterinary and human oncology centres. In conclusion, only low levels of platinum
      contamination attributable to carboplatin were found in the sampled veterinary
      oncology centres. However, dispersion of platinum outside areas where
      antineoplastic drugs were handled was detected in veterinary and human oncology
      centres. Consequently, not only personnel, but also others may be exposed to
      platinum.

PMID- 24034227
TI  - Skeletal muscle metabolic gene response to carbohydrate feeding during exercise
      in the heat.
AB  - BACKGROUND: Heat stress down-regulates mitochondrial function, while carbohydrate
      supplementation attenuates the exercise induced stimulation of mitochondrial
      biogenesis in humans. The effects of exogenous carbohydrate during exercise in
      the heat on metabolic mRNA have not been investigated in humans. The purpose of
      this study was to determine the impact of exercise with and without carbohydrate
      supplementation on skeletal muscle metabolic response in the heat. METHODS: Eight
      recreationally active males (4.05 +/- 0.2 L.min-1) completed 2 trials which
      included 1 hr of cycling at 70% workload max and 3 hr recovery in a hot
      environment. Both trials were conducted in a climate controlled environmental
      chamber (38 degrees C and 40% RH). The trials differed by the consumption of
      either a 6% carbohydrate (CHO) containing beverage (8 ml.kg-1.hr-1) or placebo
      (P) during exercise in random order. Muscle biopsies were obtained from the
      vastus lateralis before exercise, immediately post-exercise and at the end of the
      3 hr recovery period. Muscle was analyzed for muscle glycogen and mRNA related to
      metabolic and mitochondrial development (MFN2, PGC-1alpha, GLUT4, UCP3). Expired
      gases were measured to determine whole body substrate use during exercise.
      RESULTS: Carbohydrate oxidation and muscle glycogen utilization did not differ
      between trials, whereas fat oxidation was elevated during exercise in P. Exercise
      caused an increase in PGC-1alpha, and GLUT4 (P < 0.05) independent of exogenous
      carbohydrate provision. Carbohydrate consumption attenuated the mRNA response in
      UCP3 (P < 0.05). CONCLUSIONS: This study indicates that the provision of
      exogenous carbohydrate attenuates the stimulation of mRNA expression of UCP3
      following exercise in the heat.

PMID- 24034229
TI  - Abstracts of the Australasian Society of Clinical Immunology and Allergy (ASCIA)
      24th Annual Scientific Meeting. September 11-13, 2013. Perth, Australia.

PMID- 24034228
TI  - Pre-existing Schistosoma japonicum infection alters the immune response to
      Plasmodium berghei infection in C57BL/6 mice.
AB  - BACKGROUND: Since helminths and malaria parasites are often co-endemic, it is
      important to clarify the immunoregulatory mechanism that occurs during the
      process of co-infection. A previous study confirmed that dendritic cells (DCs)
      are involved in the establishment and regulation of the T-cell-mediated immune
      response to malaria infection. In the current study, distinct response profiles
      for splenic DCs and regulatory T cell (Treg) responses were assessed to evaluate
      the effects of a pre-existing Schistosoma japonicum infection on malaria
      infection. METHODS: Malaria parasitaemia, survival rate, brain histopathology and
      clinical experimental cerebral malaria (ECM) were assessed in both Plasmodium
      berghei ANKA-mono-infected and S. japonicum-P. berghei ANKA-co-infected mice.
      Cell surface/intracellular staining and flow cytometry were used to analyse the
      level of splenic DC subpopulations, toll-like receptors (TLRs), DC surface
      molecules, Tregs (CD4+CD25+Foxp3+), IFN-gamma/IL-10-secreting Tregs, and IFN
      gamma+/IL-10+-Foxp3-CD4+ T cells. IFN-gamma, IL-4, IL-5, IL-10 and IL-13 levels
      were determined in splenocyte supernatants using enzyme-linked immunosorbent
      assay (ELISA). RESULTS: The co-infected mice had significantly higher malaria
      parasitaemia, compared with the mono-infected mice, on days 2, 3, 7 and 8 after
      P. berghei ANKA infection. Mono-infected mice had a slightly lower survival rate,
      while clinical ECM symptoms, and brain pathology, were significantly more severe
      during the period of susceptibility to ECM. On days 5 and 8 post P. berghei ANKA
      infection, co-infected mice had significantly lower levels of CD11c+CD11b+,
      CD11c+CD45R/B220+, CD11c+TLR4+, CD11c+TLR9+, CD11c+MHCII+, CD11c+CD86+, IFN-gamma
      secreting Tregs, and IFN-gamma+Foxp3-CD4+ T cells in single-cell suspensions of
      splenocytes when compared with P. berghei ANKA-mono-infected mice. Co-infected
      mice also had significantly lower levels of IFN-gamma and higher levels of IL-4,
      IL-5, and IL-13 in splenocyte supernatants compared to mono-infected mice. There
      were no differences in the levels of IL-10-secreting Tregs or IL-10+Foxp3-CD4+ T
      cells between co-infected and mono-infected mice. CONCLUSIONS: A Tregs-associated
      Th2 response plays an important role in protecting against ECM pathology. Pre
      existing S. japonicum infection suppressed TLR ligand-induced DC maturation and
      had an anti-inflammatory effect during malaria infection not only by virtue of
      its ability to induce Th2 responses, but also by directly suppressing the ability
      of DC to produce pro-inflammatory mediators.

PMID- 24034231
TI  - Donor cancer transmission in kidney transplantation: a systematic review.
AB  - Transplantation of any biological material from a donor to a host will carry some
      inherent risk of disease transmission. Our aims were to summarize the totality of
      the published evidence about donor cancer transmission among kidney transplant
      recipients and to determine the cancer-specific survival of these patients. We
      systematically reviewed all case reports, case series and registry studies that
      described the outcomes of kidney transplant recipients with donor cancer
      transmission published to December 2012. A total of 69 studies with 104 donor
      transmitted cancer cases were identified. The most common transmitted cancer
      types were renal cancer (n = 20, 19%), followed by melanoma (n = 18, 17%),
      lymphoma (n = 15, 14%) and lung cancer (n = 9, 9%). Patients with melanoma and
      lung cancers had the worst prognosis, with less than 50% of recipients surviving
      after 24 months from transplantation. Recipients with transmitted renal cancers
      had the best outcomes, with over 70% of recipients surviving for at least 24
      months after transplantation. Overall, the risk of donor transmission of cancer
      appears low, but there is a high likelihood of reporting bias. Our findings
      support the current recommendations for rejecting organs from donors with a
      history of melanoma and lung cancer, but suggest that the use of donor kidneys
      with a history of small, incidental renal cell cancer may be reasonable.

PMID- 24034230
TI  - Application of quantitative second-line drug susceptibility testing at a
      multidrug-resistant tuberculosis hospital in Tanzania.
AB  - BACKGROUND: Lack of rapid and reliable susceptibility testing for second-line
      drugs used in the treatment of multidrug-resistant tuberculosis (MDR-TB) may
      limit treatment success. METHODS: Mycobacterium tuberculosis isolates from
      patients referred to Kibong'oto National TB Hospital in Tanzania for second-line
      TB treatment underwent confirmatory speciation and susceptibility testing.
      Minimum inhibitory concentration (MIC) testing on MYCOTB Sensititre plates was
      performed for all drugs available in the second-line formulary. We chose to
      categorize isolates as borderline susceptible if the MIC was at or one dilution
      lower than the resistance breakpoint. M. tuberculosis DNA was sequenced for
      resistance mutations in rpoB (rifampin), inhA (isoniazid, ethionamide), katG
      (isoniazid), embB (ethambutol), gyrA (fluoroquinolones), rrs (amikacin,
      kanamycin, capreomycin), eis (kanamycin) and pncA (pyrazinamide). RESULTS: Of 22
      isolates from patients referred for second-line TB treatment, 13 (59%) were MDR
      TB and the remainder had other resistance patterns. MIC testing identified 3
      (14%) isolates resistant to ethionamide and another 8 (36%) with borderline
      susceptibility. No isolate had ofloxacin resistance, but 10 (45%) were borderline
      susceptible. Amikacin was fully susceptible in 15 (68%) compared to only 11 (50%)
      for kanamycin. Resistance mutations were absent in gyrA, rrs or eis for all 13
      isolates available for sequencing, but pncA mutation resultant in amino acid
      change or stop codon was present in 6 (46%). Ten (77%) of MDR-TB patients had at
      least one medication that could have logically been modified based on these
      results (median 2; maximum 4). The most common modifications were a change from
      ethioniamide to para-aminosalicylic acid, and the use of higher dose
      levofloxacin. CONCLUSIONS: In Tanzania, quantitative second-line susceptibility
      testing could inform and alter MDR-TB management independent of drug-resistance
      mutations. Further operational studies are warranted.

PMID- 24034232
TI  - Primary hepatic aspergillosis following induction chemotherapy for acute
      leukemia.
AB  - Invasive aspergillosis (IA) contributes significantly to the burden of infectious
      complications in heavily immunosuppressed patients with acute leukemia. The
      infection is typically acquired via inhalation into the respiratory tract, and
      the lungs are most commonly involved. However, disseminated disease may occur and
      reports of isolated extrapulmonary infection suggest the gastrointestinal tract
      is likely an additional portal of entry for this organism. We describe a case of
      primary hepatic aspergillosis in a patient with acute myelogenous leukemia. The
      patient did not respond to medical therapy with antifungals and ultimately
      required surgical exploration and drainage. IA should be considered in an
      immunosuppressed patient with hepatic abscesses and may require a combined
      surgical and medical approach to therapy. 

PMID- 24034233
TI  - Cultural relevance of the quality-of-life tools for people with kidney failure.
AB  - BACKGROUND: Many tools are used to examine the Quality of Life (QOL) of patients
      with kidney disease, but little is known about how culturally relevant they are
      and why one should utilise one tool over another. As part of a larger study on
      the QOL of dialysis patients in United Arab Emirates, the cultural relevance of
      two tools (SF-36 and the QOL Index) was examined. This paper suggests a model to
      establish cultural relevance of QOL tools. METHOD: A descriptive comparative
      survey design using a mixed method design was used in 2007 to study the QOL of
      161 patients on dialysis and 350 people from the community. The cultural
      relevance of each tool was assessed by (i) examining missed questions, (ii)
      asking respondents about the cultural relevance of each tool, (iii) asking
      respondents what questions could be added or deleted to make the tools more
      culturally relevant and (iv) asking respondents to identify the factors that
      might contribute to their QOL. RESULTS: Of respondents, 94.7% from the dialysis
      sample and 90.4% from the community sample considered both tools culturally
      relevant. The QOL Index tool had more missing data. Many of the themes generated
      from the analysis of the qualitative data were addressed by the subscales of both
      tools. Themes not addressed by either tool were concerned with values, safety and
      country. CONCLUSION: Cultural adaptation of QOL tools needs to follow well
      established guidelines. The target population should be involved in establishing
      the cultural relevance of QOL tools.

PMID- 24034234
TI  - Single institution's dosimetry and IGRT analysis of prostate SBRT.
AB  - BACKGROUND AND PURPOSE: To report single institution's IGRT and dosimetry
      analysis on the 37 Gy/5 fraction prostate SBRT clinical trial. MATERIALS/METHODS:
      The IRB (Duke University Medical Center) approved clinical trial has treated 28
      patients with stage T1-T2c prostate cancer with a regimen of 37 Gy in 5 fractions
      using IMRT and IGRT protocols since 2009. The clinical trial protocol requires
      CT/MRI imaging for the prostate delineation; a margin of 3 mm in posterior
      direction and 5 mm elsewhere for planning target volume (PTV); and strict dose
      constraints for primary organs-at-risks (OARs) including the bladder, the rectum,
      and the femoral heads. Rigid IGRT process is also an essential part of the
      protocol. Precise patient and prostate positioning and dynamic tracking of
      prostate motion are performed with electromagnetic localization device (Calypso)
      and on-board imaging (OBI) system. Initial patient and target alignment is
      performed based on fiducials with OBI imaging system and Calypso system. Prior to
      treatment, cone-beam CT (CBCT) is performed for soft tissue alignment
      verification. During treatment, per-beam corrections for target motion using
      translational couch movements is performed before irradiating each field, based
      on electromagnetic localization or on-board imaging localization. Dosimetric
      analysis on target coverage and OAR sparing is performed based on key DVH
      parameters corresponding to protocol guidance. IGRT analysis is focused on the
      average frequency and magnitude of corrections during treatment, and overall
      intra-fractional target drift. A margin value is derived using actual target
      motion data and the margin recipe from Van Herk et al., and is compared to the
      current one in practice. In addition, cumulative doses with and without per-beam
      IGRT corrections are compared to assess the benefit of online IGRT. RESULTS: 1.
      No deviation has been found in 10 of 14 dosimetric constraints, with minor
      deviations in the rest 4 constraints.2. Online IGRT techniques including Calypso,
      OBI and CBCT supplement each other to create an effective and reliable system on
      tracking target and correcting intra-fractional motion.3. On average 1/2
      corrections have been performed per fraction, with magnitude of (0.22 +/- 0.11)
      cm. Average target drift magnitude is (0.7 +/- 1.3) mm in one direction during
      each fraction.4. Benefit from per-beam correction in overall review is small:
      most differences from no correction are < 0.1 Gy for PTV D1cc/Dmean and < 1%/1.5
      cc for OAR parameters. Up to 1.5 Gy reduction was seen in PTV D99% without online
      correction. Largest differences for OARs are -4.1 cc and +1.6 cc in the V50% for
      the bladder and the rectum, respectively. However, online IGRT helps to catch
      unexpected significant target motion.5. Margin derived from actual target motion
      is 2.5 mm isotropic, consist with current practice. CONCLUSIONS: Clinical
      experience of the 37 Gy/5-fraction prostate SBRT from a single institution is
      reported. Dosimetric analysis demonstrated excellent target coverage and OAR
      sparing for our first 28 patients in this trial. Online IGRT techniques
      implemented are both effective and reliable. Per-beam correction in general
      provides a small benefit in dosimetry. Target motion measured by online
      localization devices confirms that current margin selection is adequate.

PMID- 24034235
TI  - Overexpression of a modified 6-phosphofructo-1-kinase results in an increased
      itaconic acid productivity in Aspergillus niger.
AB  - A modified 6-phosphofructo-1-kinase was expressed in a citrate producing
      Aspergillus niger strain in combination with cis-aconitate decarboxylase from
      Aspergillus terreus to study the effect on the production of itaconic acid. The
      modified pfkA gene was also expressed in combination with the itaconic acid
      biosynthetic cluster from A. terreus, which consists of cis-aconitate
      decarboxylase cadA, a putative mitochondrial transporter mttA and a putative
      plasmamembrane transporter mfsA. The combined expression of pfkA and cadA
      resulted in increased citrate levels, but did not show increased itaconic acid
      levels. The combined expression of pfkA with the itaconic acid biosynthetic
      cluster resulted in significantly increased itaconic acid production at earlier
      time points. Also the itaconic acid productivity increased significantly. The
      maximum itaconic acid productivity that was reached under these conditions was
      0.15 g/L/h, which is only a factor 17 lower than the 2.5 g/L/h that according to
      the US Department of Energy should be achieved to have an economically feasible
      production process. 

PMID- 24034236
TI  - Rapid release revealed: honoring the synapse.
AB  - This year, the Albert Lasker Basic Medical Research Award will be shared by
      Richard Scheller and Thomas Sudhof for their elucidation of the molecular
      mechanisms underlying neurotransmitter release. Their discoveries provided
      insight into the molecular basis of synaptic transmission and enhanced our
      understanding of how synaptic dysfunction may cause neuropsychiatric disorders. 

PMID- 24034237
TI  - A tribute to a remarkably sound solution.
AB  - For their work on the development of the modern cochlear implant, which bestows
      hearing to individuals with profound deafness, Ingeborg Hochmair, Graeme Clark,
      and Blake Wilson are the 2013 recipients of the Lasker~DeBakey Clinical Medical
      Research Award. 

PMID- 24034238
TI  - Every life has equal value.
AB  - The 2013 Lasker~Bloomberg Public Service Award will be given to Bill and Melinda
      Gates "for leading an historic transformation in the way we view the globe's most
      pressing health concerns and improving the lives of millions of the world's most
      vulnerable." 

PMID- 24034239
TI  - A template for new drugs against Alzheimer's disease.
AB  - Alzheimer's disease (AD) is associated with the deposition of beta-amyloid
      (Abeta) plaques in the brain. In this issue, by cleverly processing patient
      samples, Lu et al. define a novel structural model of Abeta fibrils from AD
      brain, revealing surprising differences from in vitro fibrils. These findings may
      lead to structure-specific inhibitors and more selective amyloid-imaging methods.

PMID- 24034240
TI  - Self-eating limits EGFR-dependent tumor growth.
AB  - Autophagy is a cell-autonomous, catabolic process that plays context-dependent
      roles in tumor growth and progression. Wei et al. report that EGFR signaling
      promotes tumor growth through phosphorylation and functional inactivation of
      Beclin 1 and the consequent suppression of autophagy.

PMID- 24034241
TI  - Intrinsic activity of odorant receptors guides sensory map formation.
AB  - Olfactory sensory neurons innervate the olfactory bulb in stereotyped patterns
      according to the odorant receptors they express. A study by Nakashima et al. in
      this issue demonstrates that the odorant receptor's level of intrinsic activity
      in the absence of activating odorant-influences the guidance of olfactory axons
      to their targets.

PMID- 24034242
TI  - Motion detection: neuronal circuit meets theory.
AB  - Motion detection in fly vision has been investigated experimentally and
      theoretically for half of a century, yet mechanistic insights into the neuronal
      computation have only started to emerge. In a recent issue of Nature, two studies
      provide major insights into how motion direction is extracted from the image flow
      projected onto the retina. 

PMID- 24034243
TI  - Long noncoding RNAs usher in a new era in the biology of enhancers.
AB  - Enhancer-associated long noncoding RNAs act over long distances and across
      chromosomes to activate transcription at distal promoters. Here, we address the
      latest advances made toward understanding the role of long noncoding RNA
      expression and the involvement of these RNAs in enhancer function through
      association with protein factors and modulation of chromatin structure. 

PMID- 24034244
TI  - The regulation of cell size.
AB  - An adult animal consists of cells of vastly different size and activity, but the
      regulation of cell size remains poorly understood. Recent studies uncovering some
      of the signaling pathways important for size/growth control, together with the
      identification of diseases resulting from aberrations in these pathways, have
      renewed interest in this field. This Review will discuss our current
      understanding of how a cell sets its size, how it can adapt its size to a
      changing environment, and how these processes are relevant to human disease. 

PMID- 24034245
TI  - Structure and subunit topology of the INO80 chromatin remodeler and its
      nucleosome complex.
AB  - INO80/SWR1 family chromatin remodelers are complexes composed of >15 subunits and
      molecular masses exceeding 1 MDa. Their important role in transcription and
      genome maintenance is exchanging the histone variants H2A and H2A.Z. We report
      the architecture of S. cerevisiae INO80 using an integrative approach of electron
      microscopy, crosslinking and mass spectrometry. INO80 has an embryo-shaped head
      neck-body-foot architecture and shows dynamic open and closed conformations. We
      can assign an Rvb1/Rvb2 heterododecamer to the head in close contact with the
      Ino80 Snf2 domain, Ies2, and the Arp5 module at the neck. The high-affinity
      nucleosome-binding Nhp10 module localizes to the body, whereas the module that
      contains actin, Arp4, and Arp8 maps to the foot. Structural and biochemical
      analyses indicate that the nucleosome is bound at the concave surface near the
      neck, flanked by the Rvb1/2 and Arp8 modules. Our analysis establishes a
      structural and functional framework for this family of large remodelers.

PMID- 24034246
TI  - Molecular architecture of the ATP-dependent chromatin-remodeling complex SWR1.
AB  - The ATP-dependent chromatin-remodeling complex SWR1 exchanges a variant histone
      H2A.Z/H2B dimer for a canonical H2A/H2B dimer at nucleosomes flanking histone
      depleted regions, such as promoters. This localization of H2A.Z is conserved
      throughout eukaryotes. SWR1 is a 1 megadalton complex containing 14 different
      polypeptides, including the AAA+ ATPases Rvb1 and Rvb2. Using electron
      microscopy, we obtained the three-dimensional structure of SWR1 and mapped its
      major functional components. Our data show that SWR1 contains a single
      heterohexameric Rvb1/Rvb2 ring that, together with the catalytic subunit Swr1,
      brackets two independently assembled multisubunit modules. We also show that SWR1
      undergoes a large conformational change upon engaging a limited region of the
      nucleosome core particle. Our work suggests an important structural role for the
      Rvbs and a distinct substrate-handling mode by SWR1, thereby providing a
      structural framework for understanding the complex dimer-exchange reaction.

PMID- 24034247
TI  - Nucleosome-free region dominates histone acetylation in targeting SWR1 to
      promoters for H2A.Z replacement.
AB  - The histone variant H2A.Z is a genome-wide signature of nucleosomes proximal to
      eukaryotic regulatory DNA. Whereas the multisubunit chromatin remodeler SWR1 is
      known to catalyze ATP-dependent deposition of H2A.Z, the mechanism of SWR1
      recruitment to S. cerevisiae promoters has been unclear. A sensitive assay for
      competitive binding of dinucleosome substrates revealed that SWR1 preferentially
      binds long nucleosome-free DNA and the adjoining nucleosome core particle,
      allowing discrimination of gene promoters over gene bodies. Analysis of mutants
      indicates that the conserved Swc2/YL1 subunit and the adenosine triphosphatase
      domain of Swr1 are mainly responsible for binding to substrate. SWR1 binding is
      enhanced on nucleosomes acetylated by the NuA4 histone acetyltransferase, but
      recognition of nucleosome-free and nucleosomal DNA is dominant over interaction
      with acetylated histones. Such hierarchical cooperation between DNA and histone
      signals expands the dynamic range of genetic switches, unifying classical gene
      regulation by DNA-binding factors with ATP-dependent nucleosome remodeling and
      posttranslational histone modifications.

PMID- 24034248
TI  - SWR-C and INO80 chromatin remodelers recognize nucleosome-free regions near +1
      nucleosomes.
AB  - SWR-C/SWR1 and INO80 are multisubunit complexes that catalyze the deposition and
      removal, respectively, of histone variant H2A.Z from the first nucleosome at the
      start of genes. How they target and engage these +1 nucleosomes is unclear. Using
      ChIP-exo, we identified the subnucleosomal placement of 20 of their subunits
      across the yeast genome. The Swc2 subunit of SWR-C bound a narrowly defined
      region in the adjacent nucleosome-free region (NFR), where it positioned the Swr1
      subunit over one of two sites of H2A.Z deposition at +1. The genomic binding maps
      suggest that many subunits have a rather plastic organization that allows
      subunits to exchange between the two complexes. One outcome of promoting
      H2A/H2A.Z exchange was an enhanced turnover of entire nucleosomes, thereby
      creating dynamic chromatin at the start of genes. Our findings provide unifying
      concepts on how these two opposing chromatin remodeling complexes function
      selectively at the +1 nucleosome of nearly all genes.

PMID- 24034249
TI  - Molecular structure of beta-amyloid fibrils in Alzheimer's disease brain tissue.
AB  - In vitro, beta-amyloid (Abeta) peptides form polymorphic fibrils, with molecular
      structures that depend on growth conditions, plus various oligomeric and
      protofibrillar aggregates. Here, we investigate structures of human brain-derived
      Abeta fibrils, using seeded fibril growth from brain extract and data from solid
      state nuclear magnetic resonance and electron microscopy. Experiments on tissue
      from two Alzheimer's disease (AD) patients with distinct clinical histories
      showed a single predominant 40 residue Abeta (Abeta40) fibril structure in each
      patient; however, the structures were different from one another. A molecular
      structural model developed for Abeta40 fibrils from one patient reveals features
      that distinguish in-vivo- from in-vitro-produced fibrils. The data suggest that
      fibrils in the brain may spread from a single nucleation site, that structural
      variations may correlate with variations in AD, and that structure-specific
      amyloid imaging agents may be an important future goal.

PMID- 24034250
TI  - EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor
      progression, and tumor chemoresistance.
AB  - Cell surface growth factor receptors couple environmental cues to the regulation
      of cytoplasmic homeostatic processes, including autophagy, and aberrant
      activation of such receptors is a common feature of human malignancies. Here, we
      defined the molecular basis by which the epidermal growth factor receptor (EGFR)
      tyrosine kinase regulates autophagy. Active EGFR binds the autophagy protein
      Beclin 1, leading to its multisite tyrosine phosphorylation, enhanced binding to
      inhibitors, and decreased Beclin 1-associated VPS34 kinase activity. EGFR
      tyrosine kinase inhibitor (TKI) therapy disrupts Beclin 1 tyrosine
      phosphorylation and binding to its inhibitors and restores autophagy in non-small
      cell lung carcinoma (NSCLC) cells with a TKI-sensitive EGFR mutation. In NSCLC
      tumor xenografts, the expression of a tyrosine phosphomimetic Beclin 1 mutant
      leads to reduced autophagy, enhanced tumor growth, tumor dedifferentiation, and
      resistance to TKI therapy. Thus, oncogenic receptor tyrosine kinases directly
      regulate the core autophagy machinery, which may contribute to tumor progression
      and chemoresistance.

PMID- 24034251
TI  - Diverse autophagosome membrane sources coalesce in recycling endosomes.
AB  - Autophagic protein degradation is mediated by autophagosomes that fuse with
      lysosomes, where their contents are degraded. The membrane origins of
      autophagosomes may involve multiple sources. However, it is unclear if and where
      distinct membrane sources fuse during autophagosome biogenesis. Vesicles
      containing mATG9, the only transmembrane autophagy protein, are seen in many
      sites, and fusions with other autophagic compartments have not been visualized in
      mammalian cells. We observed that mATG9 traffics from the plasma membrane to
      recycling endosomes in carriers that appear to be routed differently from ATG16L1
      containing vesicles, another source of autophagosome membrane. mATG9- and ATG16L1
      containing vesicles traffic to recycling endosomes, where VAMP3-dependent
      heterotypic fusions occur. These fusions correlate with autophagosome formation,
      and both processes are enhanced by perturbing membrane egress from recycling
      endosomes. Starvation, a primordial autophagy activator, reduces membrane
      recycling from recycling endosomes and enhances mATG9-ATG16L1 vesicle fusion.
      Thus, this mechanism may fine-tune physiological autophagic responses.

PMID- 24034252
TI  - Dynein recruitment to nuclear pores activates apical nuclear migration and
      mitotic entry in brain progenitor cells.
AB  - Radial glial progenitors (RGPs) are elongated epithelial cells that give rise to
      neurons, glia, and adult stem cells during brain development. RGP nuclei migrate
      basally during G1, apically using cytoplasmic dynein during G2, and undergo
      mitosis at the ventricular surface. By live imaging of in utero electroporated
      rat brain, we find that two distinct G2-specific mechanisms for dynein nuclear
      pore recruitment are essential for apical nuclear migration. The "RanBP2-BicD2"
      and "Nup133-CENP-F" pathways act sequentially, with Nup133 or CENP-F RNAi
      arresting nuclei close to the ventricular surface in a premitotic state. Forced
      targeting of dynein to the nuclear envelope rescues nuclear migration and cell
      cycle progression, demonstrating that apical nuclear migration is not simply
      correlated with cell-cycle progression from G2 to mitosis, but rather, is a
      required event. These results reveal that cell-cycle control of apical nuclear
      migration occurs by motor protein recruitment and identify a role for nucleus-
      and centrosome-associated forces in mitotic entry. PAPERCLIP: 

PMID- 24034253
TI  - Agonist-independent GPCR activity regulates anterior-posterior targeting of
      olfactory sensory neurons.
AB  - G-protein-coupled receptors (GPCRs) are known to possess two different
      conformations, active and inactive, and they spontaneously alternate between the
      two in the absence of ligands. Here, we analyzed the agonist-independent GPCR
      activity for its possible role in receptor-instructed axonal projection. We
      generated transgenic mice expressing activity mutants of the beta2-adrenergic
      receptor, a well-characterized GPCR with the highest homology to odorant
      receptors (ORs). We found that mutants with altered agonist-independent activity
      changed the transcription levels of axon-targeting molecules--e.g., Neuropilin-1
      and Plexin-A1--but not of glomerular segregation molecules--e.g., Kirrel2 and
      Kirrel3--thus causing shifts in glomerular locations along the anterior-posterior
      (A-P) axis. Knockout and in vitro experiments demonstrated that Gs, but not Golf,
      is responsible for mediating the agonist-independent GPCR activity. We conclude
      that the equilibrium of conformational transitions set by each OR is the major
      determinant of expression levels of A-P-targeting molecules.

PMID- 24034254
TI  - Lck availability during thymic selection determines the recognition specificity
      of the T cell repertoire.
AB  - Thymic selection requires signaling by the protein tyrosine kinase Lck to
      generate T cells expressing alphabeta T cell antigen receptors (TCR). For reasons
      not understood, the thymus selects only alphabetaTCR that are restricted by major
      histocompatibility complex (MHC)-encoded determinants. Here, we report that Lck
      proteins that were coreceptor associated promoted thymic selection of
      conventionally MHC-restricted TCR, but Lck proteins that were coreceptor free
      promoted thymic selection of MHC-independent TCR. Transgenic TCR with MHC
      independent specificity for CD155 utilized coreceptor-free Lck to signal thymic
      selection in the absence of MHC, unlike any transgenic TCR previously described.
      Thus, the thymus can select either MHC-restricted or MHC-independent alphabetaTCR
      depending on whether Lck is coreceptor associated or coreceptor free. We conclude
      that the intracellular state of Lck determines the specificity of thymic
      selection and that Lck association with coreceptor proteins during thymic
      selection is the mechanism by which MHC restriction is imposed on a randomly
      generated alphabetaTCR repertoire.

PMID- 24034256
TI  - High-content siRNA screen reveals global ENaC regulators and potential cystic
      fibrosis therapy targets.
AB  - Dysfunction of ENaC, the epithelial sodium channel that regulates salt and water
      reabsorption in epithelia, causes several human diseases, including cystic
      fibrosis (CF). To develop a global understanding of molecular regulators of ENaC
      traffic/function and to identify of candidate CF drug targets, we performed a
      large-scale screen combining high-content live-cell microscopy and siRNAs in
      human airway epithelial cells. Screening over 6,000 genes identified over 1,500
      candidates, evenly divided between channel inhibitors and activators. Genes in
      the phosphatidylinositol pathway were enriched on the primary candidate list, and
      these, along with other ENaC activators, were examined further with secondary
      siRNA validation. Subsequent detailed investigation revealed ciliary neurotrophic
      factor receptor (CNTFR) as an ENaC modulator and showed that inhibition of
      (diacylglycerol kinase, iota) DGKiota, a protein involved in PiP2 metabolism,
      downgrades ENaC activity, leading to normalization of both Na+ and fluid
      absorption in CF airways to non-CF levels in primary human lung cells from CF
      patients.

PMID- 24034255
TI  - Decoding information in cell shape.
AB  - Shape is an indicator of cell health. But how is the information in shape
      decoded? We hypothesize that decoding occurs by modulation of signaling through
      changes in plasma membrane curvature. Using analytical approaches and numerical
      simulations, we studied how elongation of cell shape affects plasma membrane
      signaling. Mathematical analyses reveal transient accumulation of activated
      receptors at regions of higher curvature with increasing cell eccentricity. This
      distribution of activated receptors is periodic, following the Mathieu function,
      and it arises from local imbalance between reaction and diffusion of soluble
      ligands and receptors in the plane of the membrane. Numerical simulations show
      that transient microdomains of activated receptors amplify signals to downstream
      protein kinases. For growth factor receptor pathways, increasing cell
      eccentricity elevates the levels of activated cytoplasmic Src and nuclear
      MAPK1,2. These predictions were experimentally validated by changing cellular
      eccentricity, showing that shape is a locus of retrievable information storage in
      cells.

PMID- 24034257
TI  - Treatment, outcome and quality of life after Fournier's gangrene: a multicentre
      study.
AB  - AIM: The object of this study was to describe the course of Fournier's gangrene
      and assess quality of life in a group of affected patients. METHOD: We evaluated
      patients who received inpatient treatment for Fournier's gangrene at five
      hospitals in northern Germany from 1995 to 2010. Surviving patients were asked to
      take part in a clinical follow-up and complete the Short-Form 36 (SF-36) quality
      of-life questionnaire and a disease-specific questionnaire including a physical
      examination. RESULTS: Of the 86 patients, 72 (83.7%) were men. The mean age of
      the patients was 57.9 +/- 13.9 (25-89) years. The mean length of hospital stay
      was 52.0 +/- 54.0 (1-329) days. Fourteen (16.3%) patients (eight men) died
      primarily from Fournier's gangrene. The most common aetiological event was
      anogenital abscess formation (n = 24; 27.9%). Seventy-one (82.5%) patients had a
      mixed polymicrobial infection. SF-36 physical role functioning (P = 0.010),
      physical functioning (P = 0.008), general health (P = 0.010) and physical health
      summary (P = 0.006) scores were significantly lower than those of the normal
      population. Deterioration in sexual function was reported by 65% of the patients.
      CONCLUSION: Patients with Fournier's gangrene experience persistent physical and
      mental health problems for a long period of time following their primary hospital
      stay and must receive long-term care from a variety of specialists, otherwise the
      disease leads to an increase in the duration of morbidity and a decrease in
      quality of life.

PMID- 24034258
TI  - Letter from the editor: Body image.

PMID- 24034259
TI  - Letter from the editor: Lung cancer screening and a terminology quiz.

PMID- 24034260
TI  - Letter from the guest editor: Thoracic neoplasia.

PMID- 24034261
TI  - Case of the season: cystic thymoma.

PMID- 24034262
TI  - Subsolid pulmonary nodule management and lung adenocarcinoma classification:
      state of the art and future trends.

PMID- 24034263
TI  - Lung cancer: positron emission tomography/computed tomography and the new staging
      system.

PMID- 24034264
TI  - Malignant pleural mesothelioma: role of CT, MRI, and PET/CT in staging evaluation
      and treatment considerations.

PMID- 24034265
TI  - Metastatic disease to the lungs and pleura: an overview.

PMID- 24034266
TI  - Esophageal malignancy and staging.

PMID- 24034267
TI  - Tracheal and airway neoplasms.

PMID- 24034269
TI  - Characterization of HOX gene expression in canine mammary tumour cell lines from
      spontaneous tumours.
AB  - Spatial/temporal controls of development are regulated by the homeotic (HOX) gene
      complex and require integration with oncogenes and tumour suppressors regulating
      cell cycle exit. Spontaneously derived neoplastic canine mammary carcinoma cell
      models were investigated to determine if HOX expression profiles were associated
      with neoplasia as HOX genes promote neoplastic potential in human cancers.
      Comparative assessment of human and canine breast cancer expression profiles
      revealed remarkable similarity for all four paralogous HOX gene clusters and
      several unlinked HOX genes. Five canine HOX genes were overexpressed with
      expression profiles consistent with oncogene-like character (HOXA1, HOXA13,
      HOXD4, HOXD9 and SIX1) and three HOX genes with underexpressed profiles (HOXA11,
      HOXC8 and HOXC9) were also identified as was an apparent nonsense mutation in
      HOXC6. This data, as well as a comparative analysis of similar data from human
      breast cancers suggested expression of selected HOX genes in canine mammary
      carcinoma could be contributing to the neoplastic phenotype. 

PMID- 24034268
TI  - Serological responses to a soluble recombinant chimeric Plasmodium vivax
      circumsporozoite protein in VK210 and VK247 population.
AB  - BACKGROUND: Circumsporozoite protein (CSP) is essential for sporozoite formation
      and sporozoite invasion into human hepatocyte. Previously, a recombinant P. vivax
      CSP based on chimeric repeats (rPvCSP-c) representing two major alleles VK210 and
      VK247 within central region has been designed. Naturally acquired humoral immune
      responses study show that antigenicity of rPvCSP-c was much higher than that of
      native strain. However, the serologic reactivity of rPvCSP-c was still unclear in
      detail. METHODS: In present study, recognition of rPvCSP-c in vivax malaria typed
      VK210 and VK247 alleles was assessed. VK210 typed and VK247 typed sera from adult
      residents reacted specifically with rPvCSP-c using protein array and immunoblot
      assay. Additionally, anti-rPvCSP-c serum recognized the fixed VK210 and VK247
      sporozoites by immunofluorescence assay. Furthermore, statistic analysis was
      performed for correlational detection. RESULTS: The rPvCSP-c reacted with both
      VK210 typed and VK247 typed P. vivax infected patient sera and anti-rPvCSP-c
      immune serum also reacted with VK210 and VK247 sporozoite parasites of P. vivax
      specifically. There was a positive correlation between increased antibody level,
      age of patients and also associated with pvcsp repeat number, although the level
      of responses did vary considerably in their reactivity to the rPvCSP-c from
      negative to very high level within each age group. CONCLUSIONS: These data
      confirmed the serologic reactivity of the novel rPvCSP-c in exposed both VK210
      and VK247 populations. These results strongly suggested that this recombinant CSP
      was biologically active and potently immunogenic across major strains and raised
      the prospect that this protein could be used as serologic marker.

PMID- 24034270
TI  - New microarchitectures of (Er,Yb):Lu2O3 nanocrystals embedded in PMMA: synthesis,
      structural characterization, and luminescent properties.
AB  - We report the formation of two-dimensional disordered arrays of
      poly(methyl)methacrylate (PMMA) microcolumns with embedded single size
      distribution of Lu0.990Er0.520Yb0.490 nanocrystals, (Er,Yb):Lu2O3, using a
      disordered porous silicon template. The cubic (Er,Yb):Lu2O3 nanocrystals, which
      crystallize into the cubic system with Ia3- space group, were synthesized using
      the modified Pechini method. Electronic microscopic techniques were used to study
      the distribution of the nanocrystals in the PMMA columns. Cathodoluminescence was
      used to observe the visible luminescence of the particles. Red emission
      attributed to 4 F9/2 -> 4I15/2 erbium transition is predominant in these new
      composites. 

PMID- 24034271
TI  - Evaluation of the effect of acute sibutramine in female rats in the elevated T
      maze and elevated plus-maze tests.
AB  - Sibutramine is a serotonin and norepinephrine reuptake inhibitor indicated for
      the treatment of obesity. A pre-clinical study showed that acute administration
      of sibutramine promoted anxiolytic- and panicolytic-like effects in male rats.
      However, in clinical reports, sibutramine favoured the onset of panic attacks in
      women. In this study, the effect of sibutramine on experimental anxiety in
      females and the relevance of different oestrous cycle phases for this effect were
      analysed. In experiment 1, both male and female rats were submitted to acute
      intraperitoneal injection of sibutramine or vehicle 30 min. before testing in the
      elevated T-maze (ETM) and in the open-field test (OF). Females in the pro-oestrus
      (P), oestrus (E), early dioestrus (ED) and late dioestrus (LD) phases were tested
      in the ETM and OF (experiment 2) or in the elevated plus-maze (EPM) 30 min. after
      the injection of sibutramine. Sibutramine impaired the escape response in the ETM
      in both males and females. This effect was observed for P, E and ED, but not for
      LD females. Sibutramine altered neither the inhibitory avoidance in the ETM nor
      the behaviour of females in the EPM. Thus, sibutramine promoted a panicolytic
      like effect in female rats cycling at P, E and ED, but not in the LD phase and
      did not alter behaviours related to anxiety in both ETM and EPM. Considering that
      pre-clinical studies aiming the screening of anxiolytic drugs employ male
      rodents, data here obtained reinforce the importance of better understanding the
      effects of drugs in females.

PMID- 24034273
TI  - Overexpression of a soybean salicylic acid methyltransferase gene confers
      resistance to soybean cyst nematode.
AB  - Salicylic acid plays a critical role in activating plant defence responses after
      pathogen attack. Salicylic acid methyltransferase (SAMT) modulates the level of
      salicylic acid by converting salicylic acid to methyl salicylate. Here, we report
      that a SAMT gene from soybean (GmSAMT1) plays a role in soybean defence against
      soybean cyst nematode (Heterodera glycines Ichinohe, SCN). GmSAMT1 was identified
      as a candidate SCN defence-related gene in our previous analysis of soybean
      defence against SCN using GeneChip microarray experiments. The current study
      started with the isolation of the full-length cDNAs of GmSAMT1 from a SCN
      resistant soybean line and from a SCN-susceptible soybean line. The two cDNAs
      encode proteins of identical sequences. The GmSAMT1 cDNA was expressed in
      Escherichia coli. Using in vitro enzyme assays, E. coli-expressed GmSAMT1 was
      confirmed to function as salicylic acid methyltransferase. The apparent Km value
      of GmSAMT1 for salicylic acid was approximately 46 MUM. To determine the role of
      GmSAMT1 in soybean defence against SCN, transgenic hairy roots overexpressing
      GmSAMT1 were produced and tested for SCN resistance. Overexpression of GmSAMT1 in
      SCN-susceptible backgrounds significantly reduced the development of SCN,
      indicating that overexpression of GmSAMT1 in the transgenic hairy root system
      could confer resistance to SCN. Overexpression of GmSAMT1 in transgenic hairy
      roots was also found to affect the expression of selected genes involved in
      salicylic acid biosynthesis and salicylic acid signal transduction.

PMID- 24034272
TI  - Perturbations to the IGF1 growth pathway and adult energy homeostasis following
      disruption of mouse chromosome 12 imprinting.
AB  - AIM: Disruption to insulin-like growth factor (IGF) signalling pathways during
      early life causes growth retardation and defects of developing metabolic organs
      that can alter set points of energy homeostasis for a lifetime. Inheritance of
      two maternal copies of human chromosome 14q32.2 (Temple syndrome) causes severe
      foetal growth retardation and post-natal failure to thrive. Disruption of
      imprinted gene dosage in the orthologous region on mouse chromosome 12 also
      affects growth. Here, we investigated whether altering chromosome 12-imprinted
      gene dosage can affect IGF signalling. METHODS: We investigated mice with a
      transgene insertion at the imprinted domain of chromosome 12. This lesion causes
      misexpression of neighbouring genes such that the expression of non-coding RNAs
      is elevated, and levels of delta-like homologue 1 (Dlk1), retrotransposon-like 1
      (Rtl1) and deiodinase 3 (Dio3) transcripts are reduced. RESULTS: We observed
      three key phenotypes in these mice: (i) embryonic growth retardation associated
      with altered expression of IGF1 binding proteins, (ii) peri-natal failure to
      thrive accompanied by hypothyroidism and low serum IGF1. Unexpectedly this
      phenotype was growth hormone independent. (iii) Adult animals had reduced glucose
      tolerance as a result of endocrine pancreatic insufficiency. CONCLUSIONS: We
      propose that all of these phenotypes are attributable to impaired IGF action and
      show for the first time that the chromosome 12 cluster in the mouse is an
      imprinted locus that modulates the IGF signalling pathway. We propose that growth
      retardation observed in human Temple syndrome might have a similar cause.

PMID- 24034275
TI  - Engendering independence while living with purpose: women's lives after leaving
      abusive intimate partners.
AB  - PURPOSE: The purpose of this study was to determine the common meanings a history
      of violence has for women out of abusive and violent relationships with an
      intimate male partner for 5 or more years. SPECIFIC AIMS: To describe the common
      meanings and shared practices of women who left violent and abusive heterosexual
      intimate relationships 5 or more years ago, the challenges they face in their
      current lives, and the resources they use to meet those challenges. An additional
      aim is to elucidate practical advice they have for others who want to be
      supportive of the efforts of women recovering from intimate partner violence.
      METHODS: An interpretive phenomenological approach using Heideggerian
      hermeneutics was utilized. Approval of the University Social Sciences
      Institutional Review Board was obtained. Participants were recruited by means of
      fliers distributed through a domestic violence listserv and through postings in
      health clinics in western New York. Interviews were recorded and transcribed. A
      hermeneutic team approach was used for analysis and interpretation of texts.
      RESULTS: Twenty-one women of various ages, ethnicities, and backgrounds, who self
      identified as being out of abusive relationships for 5 or more years, were
      interviewed. Six themes were identified: developing and maintaining self
      reliance; negotiating relationships; creating a safe and supportive environment;
      challenging societal roles and expectations; nurturing the self; and protecting
      the children. Engendering independence while living with purpose was the
      constitutive pattern that unified the themes. CONCLUSIONS: Women can successfully
      establish productive, meaningful lives after violence and will fiercely protect
      and maintain their independence as they negotiate relationships and developmental
      challenges throughout their lives. A need for control of their lives and
      difficulty trusting others remain a lasting legacy of living with a history of
      violence. CLINICAL RELEVANCE: This is the first study that examines women's lives
      5 or more years after leaving violent and abusive relationships. Findings
      indicate that women can successfully leave violent and abusive relationships, and
      challenge the widely accepted notion that women do not leave.

PMID- 24034274
TI  - Early transcriptomic adaptation to Na2CO3 stress altered the expression of a
      quarter of the total genes in the maize genome and exhibited shared and
      distinctive profiles with NaCl and high pH stresses.
AB  - Sodium carbonate (Na2CO3) presents a huge challenge to plants by the combined
      damaging effects of Na+, high pH, and CO32-. Little is known about the cellular
      responses to Na2CO3 stress. In this study, the transcriptome of maize (Zea mays
      L. cv. B73) roots exposed to Na2CO3 stress for 5 h was compared with those of
      NaCl and NaOH stresses. The expression of 8,319 genes, representing over a
      quarter of the total number of genes in the maize genome, was altered by Na2CO3
      stress, and the downregulated genes (5,232) outnumbered the upregulated genes
      (3,087). The effects of Na2CO3 differed from those of NaCl and NaOH, primarily by
      downregulating different categories of genes. Pathways commonly altered by
      Na2CO3, NaCl, and NaOH were enriched in phenylpropanoid biosynthesis, oxidation
      of unsaturated fatty acids, ATP-binding cassette (ABC) transporters, as well as
      the metabolism of secondary metabolites. Genes for brassinosteroid biosynthesis
      were specifically upregulated by Na2CO3, while genes involved in ascorbate and
      aldarate metabolism, protein processing in the endoplasmic reticulum and by N
      glycosylation, fatty acid biosynthesis, and the circadian rhythm were
      downregulated. This work provides the first holistic picture of early
      transcriptomic adaptation to Na2CO3 stress, and highlights potential molecular
      pathways that could be manipulated to improve tolerance in maize.

PMID- 24034276
TI  - A new mutation in the gene encoding mitochondrial seryl-tRNA synthetase as a
      cause of HUPRA syndrome.
AB  - BACKGROUND: HUPRA syndrome is a rare mitochondrial disease characterized by
      hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis.
      This syndrome was previously described in three patients with a homozygous
      mutation c.1169A > G (p.D390G) in SARS2, encoding the mitochondrial seryl-tRNA
      synthetase. CASE PRESENTATION: Here we report the clinical and genetic findings
      in a girl and her brother. Both patients were clinically diagnosed with the HUPRA
      syndrome. Analysis of the pedigree identified a new homozygous mutation c.1205G >
      A (p.R402H) in SARS2 gene. This mutation is very rare in the population and it is
      located at the C-terminal globular domain of the homodimeric enzyme very close to
      p.D390G. CONCLUSION: Several data support that p.R402H mutation in SARS2 is a new
      cause of HUPRA syndrome.

PMID- 24034277
TI  - Serosurvey for schmallenberg virus in alpine wild ungulates.
AB  - Because Schmallenberg virus (SBV) was first reported in domestic ruminants in
      Northern Italy in February 2012, we conducted a serosurvey to assess the presence
      of SBV-specific antibodies in free-ranging alpine ruminants. The tested serum
      samples were from chamois (23) and red deer (352) hunted from 2007 to 2013. All
      of the serum samples collected through September, 2012, tested negative, whereas
      a single chamois serum and 21 red deer sera taken during the 2012-2013 hunting
      season tested positive for the presence of SBV antibodies. Because this
      serosurvey is suggestive of an active SBV circulation in Alpine wildlife,
      targeted surveillance should be performed on wild ruminants to monitor the spread
      of the virus and to assess the epidemiological role of wildlife at the interface
      with domestic animals. 

PMID- 24034278
TI  - Comparison between kinetic modelling and graphical analysis for the
      quantification of [18F]fluoromethylcholine uptake in mice.
AB  - BACKGROUND: Until now, no kinetic model was described for the oncologic tracer
      [18F]fluoromethylcholine ([18F]FCho), so it was aimed to validate a proper model,
      which is easy to implement and allows tracer quantification in tissues. METHODS:
      Based on the metabolic profile, two types of compartmental models were evaluated.
      One is a 3C2i model, which contains three tissue compartments and two input
      functions and corrects for possible [18F]fluorobetaine ([18F]FBet) uptake by the
      tissues. On the other hand, a two-tissue-compartment model (2C1i) was evaluated.
      Moreover, a comparison, based on intra-observer variability, was made between
      kinetic modelling and graphical analysis. RESULTS: Determination of the [18F]FCho
      to-[18F]FBet uptake ratios in tissues and evaluation of the fitting of both
      kinetic models indicated that corrections for [18F]FBet uptake are not mandatory.
      In addition, [18F]FCho uptake is well described by the 2C1i model and by
      graphical analysis by means of the Patlak plot. CONCLUSIONS: The Patlak plot is a
      reliable, precise, and robust method to quantify [18F]FCho uptake independent of
      scan time or plasma clearance. In addition, it is easily implemented, even under
      non-equilibrium conditions and without creating additional errors.

PMID- 24034280
TI  - Cryptococcal meningitis presenting as sinusitis in a renal transplant recipient.
AB  - Cryptococcal meningitis is a relatively common invasive fungal infection in
      immunocompromised patients, especially in solid organ transplant recipients.
      Clinical presentation typically includes fever, headache, photophobia, neck
      stiffness, and/or altered mental status. Unusual presentations may delay
      diagnosis. Therapy is challenging in renal transplant patients because of the
      nephrotoxicity associated with amphotericin B, the recommended treatment. We
      present a case of cryptococcal meningitis in a renal transplant recipient
      presenting as acute sinusitis with successful treatment using fluconazole as
      primary therapy. 

PMID- 24034281
TI  - America's cancer care crisis.

PMID- 24034279
TI  - ACTH-independent macronodular adrenocortical hyperplasia reveals prevalent
      aberrant in vivo and in vitro responses to hormonal stimuli and coupling of
      arginine-vasopressin type 1a receptor to 11beta-hydroxylase.
AB  - BACKGROUND: Adrenal Cushing's syndrome caused by ACTH-independent macronodular
      adrenocortical hyperplasia (AIMAH) can be accompanied by aberrant responses to
      hormonal stimuli. We investigated the prevalence of adrenocortical reactions to
      these stimuli in a large cohort of AIMAH patients, both in vivo and in vitro.
      METHODS: In vivo cortisol responses to hormonal stimuli were studied in 35
      patients with ACTH-independent bilateral adrenal enlargement and (sub-)clinical
      hypercortisolism. In vitro, the effects of these stimuli on cortisol secretion
      and steroidogenic enzyme mRNA expression were evaluated in cultured AIMAH and
      other adrenocortical cells. Arginine-vasopressin (AVP) receptor mRNA levels were
      determined in the adrenal tissues. RESULTS: Positive serum cortisol responses to
      stimuli were detected in 27/35 AIMAH patients tested, with multiple responses
      within individual patients occurring for up to four stimuli. AVP and
      metoclopramide were the most prevalent hormonal stimuli triggering positive
      responses in vivo. Catecholamines induced short-term cortisol production more
      often in AIMAH cultures compared to other adrenal cells. Short- and long-term
      incubation with AVP increased cortisol secretion in cultures of AIMAH cells. AVP
      also increased steroidogenic enzyme mRNA expression, among which an aberrant
      induction of CYP11B1. AVP type 1a receptor was the only AVPR expressed and levels
      were high in the AIMAH tissues. AVPR1A expression was related to the AVP-induced
      stimulation of CYP11B1. CONCLUSIONS: Multiple hormonal signals can simultaneously
      induce hypercortisolism in AIMAH. AVP is the most prevalent eutopic signal and
      expression of its type 1a receptor was aberrantly linked to CYP11B1 expression.

PMID- 24034282
TI  - Closing the killer gap in children's health inequality.

PMID- 24034283
TI  - e-cigarettes: a moral quandary.

PMID- 24034284
TI  - Japan's strategy for global health diplomacy: why it matters.

PMID- 24034285
TI  - The Future Hospital Commission.

PMID- 24034288
TI  - Kevin Fong: medicine at the final frontier.

PMID- 24034289
TI  - Immunisation against meningococcus B.

PMID- 24034290
TI  - Immunisation against meningococcus B.

PMID- 24034291
TI  - Which future for doctors in China?

PMID- 24034293
TI  - Immunisation against meningococcus B.

PMID- 24034292
TI  - UK medical students, debt, and career choices.

PMID- 24034294
TI  - WHO's budgetary allocation and disease burden.

PMID- 24034295
TI  - Which future for doctors in China?

PMID- 24034296
TI  - Regulation of devices for cognitive enhancement.

PMID- 24034297
TI  - Kidney attack versus heart attack: evolution of classification and diagnostic
      criteria.

PMID- 24034298
TI  - Research misconduct and scientific integrity: a call for a global forum.

PMID- 24034299
TI  - Profound anaemia and acute blindness in a Jehovah's Witness.

PMID- 24034300
TI  - Water-perfused manometry vs three-dimensional high-resolution manometry: a
      comparative study on a large patient population with anorectal disorders.
AB  - AIM: Our aim was to compare for the first time measurements obtained with water
      perfused catheter anorectal manometry and three-dimensional (3D) high-resolution
      manometry in patients with anorectal disorders. METHOD: Consecutive patients
      referred to our centre for anorectal manometry (ARM) were recruited to undergo
      the two procedures successively. Conventional manometry was carried out using a
      water-perfused catheter (WPAM) and high-resolution manometry was achieved with a
      3D probe (3DHRAM). For each procedure, parameters recorded included the
      following: anal canal length, resting pressure, squeeze pressure and rectal
      sensitivity. RESULTS: Two hundred and one patients were included in this study.
      The mean values for resting and squeeze pressures were correlated and found to be
      significantly higher when measured with 3DHRAM than with WPAM. However, the
      length of the anal canal was not significantly different when measured by the two
      techniques without correlation between the two mean values obtained. The presence
      of the rectoanal inhibitory reflex was systematically assessed by both WPAM and
      3DHRAM and anismus was also systematically diagnosed by both WPAM and 3DHRAM.
      CONCLUSION: The pressure values obtained with 3DHRAM are correlated with those
      measured with conventional manometry but are systematically higher. 3DHRAM has
      the advantage of providing a pressure recording over the entire length and
      circumference of the anal canal, allowing a more useful physiological assessment
      of anorectal function.

PMID- 24034301
TI  - A case-control study of non-monitored ECG metrics preceding in-hospital
      bradyasystolic cardiac arrest: implication for predictive monitor alarms.
AB  - OBJECTIVES: We investigated whether additional electrocardiographic (ECG) metrics
      not available on current patient monitors could predict bradyasystolic cardiac
      arrest in hospitalized adult patients. METHODS: A retrospective case-control
      design was used to study eight ECG metrics from 22 adult bradyasystolic patients
      and their 45 control patients. The eight ECG metrics included heart rate, QRS
      width, interval from P-wave peak to QRS onset (PRp), heart rate-corrected
      interval from QRS onset to T-wave peak (QTpc), amplitude of QRS peak (rAmp),
      amplitude of P-wave (pAmp), amplitude of T-wave (tAmp), and absolute difference
      in the ECG amplitudes at QRS onset and offset divided by rAmp, that is, relative
      J-point amplitude (relJAmp). We derived the maximal true-positive rate (TPR) of
      detecting cardiac arrest at a globally minimal false-positive rate (FPR) for each
      metric and for the absolute slope values resulted from a linear fitting of the
      time series of these metrics. We also recorded the first time crossing the
      detection threshold to the time of arrest as lead time. RESULTS: Conditions of
      relJAmp >20% and PRp >196.6 ms, respectively, achieved a TPR of 22.7% and 27.3%
      with zero FPRs. The lead prediction time of these two conditions was 5.7 +/- 6.8
      hours and 8.0 +/- 7.2 hours, respectively. Performance of triggers based on the
      absolute slope values depended on the window length used for linear fitting. rAmp
      slope of a 2-hour window, PRp slope of a 30-minute window, and relJAmp slope of a
      2-hour window achieved the best TPR of 27.3% (FPR = 2.3%, lead time = 6.5 +/- 5.7
      hours), 14.3% (FPR=0.0%, lead time = 10.9 +/- 10.9), and 18.2% (FPR = 2.3%, lead
      time = 8.8 +/- 9.8), respectively. McNemar test showed that only relJAmp >20.0%
      is significantly different from the baseline trigger of HR >149.3 bpm (p=0.046).
      In addition, metrics-based and slope-based triggers were complementary as an "OR"
      combination of two single-metric triggers raised the TPR up to 45.4% with zero
      FPR. CONCLUSIONS: It is feasible to compute additional metrics from continuous
      ECG from bedside monitors. These additional parameters can provide highly
      specific triggers for predicting bradyasystolic cardiac arrest. Complementary
      triggers based on the slope of trending of these ECG metrics can further increase
      the sensitivity without incurring false positives.

PMID- 24034302
TI  - QRS analysis using wavelet transformation for the prediction of response to
      cardiac resynchronization therapy: a prospective pilot study.
AB  - BACKGROUND: Wider QRS and left bundle branch block morphology are related to
      response to cardiac resynchronization therapy (CRT). A novel time-frequency
      analysis of the QRS complex may provide additional information in predicting
      response to CRT. METHODS: Signal-averaged electrocardiograms were prospectively
      recorded, before CRT, in orthogonal leads and QRS decomposition in three
      frequency bands was performed using the Morlet wavelet transformation. RESULTS:
      Thirty eight patients (age 65+/-10years, 31 males) were studied. CRT responders
      (n=28) had wider baseline QRS compared to non-responders and lower QRS energies
      in all frequency bands. The combination of QRS duration and mean energy in the
      high frequency band had the best predicting ability (AUC 0.833, 95%CI 0.705
      0.962, p=0.002) followed by the maximum energy in the high frequency band (AUC
      0.811, 95%CI 0.663-0.960, p=0.004). CONCLUSIONS: Wavelet transformation of the
      QRS complex is useful in predicting response to CRT.

PMID- 24034305
TI  - Personalized medicine and the role of health economics and outcomes research:
      issues, applications, emerging trends, and future research.
AB  - The decade since the completion of the sequencing of the human genome has
      witnessed significant advances in the incorporation of genomic information in
      diagnostic, treatment, and reimbursement practices. Indeed, as case in point,
      there are now several dozen commercially available genomic tests routinely
      applied across a wide range of disease states in predictive or prognostic
      applications. Moreover, many involved in the advancement of personalized medicine
      would view emerging approaches to stratify patients in meaningful ways beyond
      genomic information as a signal of the progress made. Yet despite these advances,
      there remains a general sense of dissatisfaction about the progress of
      personalized medicine in terms of its contribution to the drug development
      process, to the efficiency and effectiveness of health care delivery, and
      ultimately to the provision of the right treatment to the right patient at the
      right time. Academicians, payers, and manufacturers alike are struggling not only
      with how to embed the new insights that personalized medicine promises but also
      with the fundamental issues of application in early drug development,
      implications for health technology assessment, new demands on traditional health
      economic and outcomes research methods, and implications for reimbursement and
      access. In fact, seemingly prosaic issues such as the definition and composition
      of the term "personalized medicine" are still unresolved. Regardless of these
      issues, practitioners are increasingly compelled to find practical solutions to
      the challenges and opportunities presented by the evolving face of personalized
      medicine today. Accordingly, the articles comprising this Special Issue offer
      applied perspectives geared toward professionals and policymakers in the field
      grappling with developing, assessing, implementing, and reimbursing personalized
      medicine approaches. Starting with a framework with which to characterize
      personalized medicine, this Special Issue proceeds to illuminate issues related
      to the intersection of personalized medicine and comparative effectiveness; use
      of personalized medicine approaches in drug development; methodological
      challenges; and payer approaches to evaluation and reimbursement of
      pharmacodiagnostics in the United States and Europe. It concludes with a look
      ahead, underscoring current controversies yet to be resolved along with their
      implications for further research and policy. It is hoped that these articles
      will help inform the daily challenges faced by the International Society for
      Pharmacoeconomics and Outcomes Research (ISPOR) community as it collectively
      addresses what promises to be a new era in drug development and health care
      delivery. 

PMID- 24034304
TI  - Effects of short-term fructooligosaccharide intake on equol production in
      Japanese postmenopausal women consuming soy isoflavone supplements: a pilot
      study.
AB  - BACKGROUND: Recent studies suggest that some of the clinical effectiveness of soy
      or daidzein, which is a type of isoflavone, may be attributed to a person's
      ability to produce equol from daidzein. Equol, which is a metabolite of one of
      the major soybean isoflavones called daidzein, is produced in the
      gastrointestinal tract by certain intestinal microbiota where present. Habitual
      dietary patterns may alter the intestinal bacterial profile, and influence the
      metabolism of isoflavones and the production of equol. Fructooligosaccharides
      (FOS) have a prebiotic activity as well as being a dietary fibre. The purpose of
      the present study was to determine whether FOS supplementation increases equol
      production in equol producers and stimulates equol production in equol non
      producers in Japanese postmenopausal women. METHODS: A soy challenge was used to
      assess equol-producer status prior to the start of the study in healthy
      postmenopausal Japanese women. The study involved 4 separate groups in randomised
      crossover design. First, subjects were classified as equol producers (n = 25) or
      non-producers (n = 18), and then they were randomly assigned to the FOS or
      control group. All subjects received a daily dose of 37 mg isoflavone conjugates
      in the capsule (21 mg aglycone form) and either FOS (5 g/day) or sucrose as
      control, in a randomised crossover study design. Equol -production was assessed
      by testing the serum and urine before and after the 2-week supplementation
      period. RESULTS: The analyses were conducted on 34 subjects completed the study,
      21 (61.8%) were classified as equol producers, and 13 (38.2%) as non-producers.
      Significant differences were observed in the interaction effect of time * equol
      state after 1 week of intervention (p = 0.006). However there were no effects
      after 2 weeks of intervention (p = 0.516). Finally, in both equol producers and
      non-producers, FOS supplementation did not affect the serum equol concentration
      or the urinary equol to daidzein concentration ratios. CONCLUSIONS: We have
      reported that FOS intervention (5 g/day for 2 weeks) does not significantly
      modulate the capacity of intestinal microbiota to produce equol in postmenopausal
      Japanese women, in either equol producers or non-producers in this pilot study.
      Further larger investigations that explore the roles of specific intestinal
      microbiota in equol production will enable the establishment of dietary
      conditions that are required to enhance equol production.

PMID- 24034303
TI  - Protein crystallography for aspiring crystallographers or how to avoid pitfalls
      and traps in macromolecular structure determination.
AB  - The number of macromolecular structures deposited in the Protein Data Bank now
      approaches 100,000, with the vast majority of them determined by crystallographic
      methods. Thousands of papers describing such structures have been published in
      the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been
      awarded for discoveries based on macromolecular crystallography. New hardware and
      software tools have made crystallography appear to be an almost routine (but
      still far from being analytical) technique and many structures are now being
      determined by scientists with very limited experience in the practical aspects of
      the field. However, this apparent ease is sometimes illusory and proper
      procedures need to be followed to maintain high standards of structure quality.
      In addition, many noncrystallographers may have problems with the critical
      evaluation and interpretation of structural results published in the scientific
      literature. The present review provides an outline of the technical aspects of
      crystallography for less experienced practitioners, as well as information that
      might be useful for users of macromolecular structures, aiming to show them how
      to interpret (but not overinterpret) the information present in the coordinate
      files and in their description. A discussion of the extent of information that
      can be gleaned from the atomic coordinates of structures solved at different
      resolution is provided, as well as problems and pitfalls encountered in structure
      determination and interpretation.

PMID- 24034306
TI  - Melding regulatory, pharmaceutical industry, and U.S. payer perspectives on
      improving approaches to heterogeneity of treatment effect in research and
      practice.
AB  - Effective pursuit of the science and management of heterogeneity of treatment
      effect (HTE) relies on the mutual understanding of the perspectives of, and
      collaboration among, the various stakeholders in health care. In this article, we
      compare, contrast, and endeavor to find areas of alignment across the
      perspectives of three such stakeholders -regulators, the biopharmaceutical and
      device industry, and U.S. payers. First, we discuss how evidence of HTE is
      generated and could be improved upon. For pharmaceuticals, much of the initial
      research is conducted by the pharmaceutical industry, guided by basic science but
      also delimited by potential markets, regulatory approval requirements, trial size
      considerations, and payer expectations for evidence of value. Once a drug is
      marketed, further evidence can be generated via combining trial data, conducting
      meta-analysis, and analyzing real-world results through observational research
      designs; we explore how these efforts can benefit from cooperation across these
      stakeholders. Second, we discuss the equally important utilization of HTE
      evidence so that physicians and patients have access to and can benefit from the
      learnings from this research. Research findings must be translated into
      actionable information and guidelines that can be incorporated into everyday
      practice. Doing so requires interaction and collaboration among all involved,
      based on facilitated communication as well as further evaluation research. We
      provide examples of several cross-sectorial initiatives that are under way in
      this area. Finally, we explore some economic aspects of HTE research as part of
      the drug development, marketing, and treatment process. Understanding the
      economic incentives present is fundamental to aligning those incentives to
      improve the availability and utilization of HTE evidence. Clear understandings
      among regulators, pharma, and payers about high-value targets, methods to
      efficiently generate and communicate information, and value propositions can lead
      to "win-win" scenarios for patients, individual payers, the health care system
      overall, and the future of drug development in producing new medicines. 

PMID- 24034307
TI  - Value-based assessment of pharmacodiagnostic testing from early stage development
      to real-world use.
AB  - Disease etiology may be regarded as a consequence of both genotypic and
      biochemical phenomena, which impact individual patients in different ways.
      Disease prognosis, beneficial treatment response, and susceptibility to adverse
      drug effects are often intimately tied to individual biology. Clinical and
      genetic biomarkers applied individually or in concert are increasingly used to
      stratify patient populations in terms of prognosis, therapeutic benefit, or
      safety. As a result, clinical trialists are challenged to design studies that
      reflect these determinants of outcome, to optimize the patient's eventual
      clinical course both in the trial and in actual practice. These designs are
      informed both by preclinical studies and by real-world research that can
      establish proof of concept for a novel biomarker and provide a basic
      understanding of the relationship between biomarker and clinical outcome. As
      clinical and real-world studies unfold, a deeper understanding of the nature of
      the biomarker and its potential uses in drug development is gained. Specifically,
      one can eventually define the biomarker as prognostic (i.e., predicts disease
      progression), predictive (predicts treatment response or adverse outcome(s)), or
      exhibiting both prognostic and predictive properties. One must further validate
      the performance of these emerging biomarkers, again in both the trial and real
      world environments. The eventual adoption of the biomarker as a useful
      pharmacodiagnostic test is premised upon this early translational research. In
      this article, the development and validation of predictive and prognostic
      biomarkers is discussed by using selected examples that highlight factors
      contributing to the valuation of biomarkers and their application to personalized
      medicine in the real world. 

PMID- 24034308
TI  - Current methodological issues in the economic assessment of personalized
      medicine.
AB  - There is a need for methodological scrutiny in the economic assessment of
      personalized medicine. In this article, we present a list of 10 specific issues
      that we argue pose specific methodological challenges that require careful
      consideration when designing and conducting robust model-based economic
      evaluations in the context of personalized medicine. Key issues are related to
      the correct framing of the research question, interpretation of test results,
      data collection of medical management options after obtaining test results, and
      expressing the value of tests. The need to formulate the research question
      clearly and be explicit and specific about the technology being evaluated is
      essential because various test kits can have the same purpose and yet differ in
      predictive value, costs, and relevance to practice and patient populations. The
      correct reporting of sensitivity/specificity, and especially the false negatives
      and false positives (which are population dependent), of the investigated tests
      is also considered as a key element. This requires additional structural
      complexity to establish the relationship between the test result and the
      consecutive treatment changes and outcomes. This process involves translating the
      test characteristics into clinical utility, and therefore outlining the clinical
      and economic consequences of true and false positives and true and false
      negatives. Information on treatment patterns and on their costs and outcomes,
      however, is often lacking, especially for false-positive and false-negative test
      results. The analysis can even become very complex if different tests are
      combined or sequentially used. This potential complexity can be handled by
      explicitly showing how these tests are going to be used in practice and then
      working with the combined sensitivities and specificities of the tests. Each of
      these issues leads to a higher degree of uncertainty in economic models designed
      to assess the added value of personalized medicine compared with their simple
      pharmaceutical counterparts. To some extent, these problems can be overcome by
      performing early population-level simulations, which can lead to the
      identification and collection of data on critical input parameters. Finally, it
      is important to understand that a test strategy does not necessarily lead to more
      quality-adjusted life-years (QALYs). It is possible that the test will lead to
      not only fewer QALYs but also fewer costs, which can be defined as "decremental"
      cost per QALYs. Different decision criteria are needed to interpret such results.

PMID- 24034310
TI  - Reflections on market access for personalized medicine: recommendations for
      Europe.
AB  - This article aims to provide an overview of the current literature focusing on
      the reimbursement of personalized medicine across the European Union. The article
      starts by describing types of perspectives that are possible (general public,
      patient, payer, provider, service commissioner, and policymaker). The description
      of perspectives also explains the importance of understanding the different
      possible decision criteria and processes from the various perspectives by taking
      into account budget constraints. The article then focuses on an example of
      personalized medicine, namely, the use of companion diagnostic-medicine
      combinations, to describe the role of reimbursement/payer agencies across the
      European Union to control the introduction and coverage of such companion
      diagnostic-medicine technologies. The article touches on the strategic challenges
      and the use of economic evidence to introduce personalized medicine from a health
      policy perspective. The article also draws on empirical studies that have
      explored patients' and clinicians' views of examples of personalized medicine to
      illustrate the challenges for developing patient-centered and timely health care
      services. 

PMID- 24034309
TI  - Regulation, reimbursement, and the long road of implementation of personalized
      medicine--a perspective from the United States.
AB  - There is undisputed evidence that personalized medicine, that is, a more precise
      assessment of which medical intervention might best serve an individual patient
      on the basis of novel technology, such as molecular profiling, can have a
      significant impact on clinical outcomes. The field, however, is still new, and
      the demonstration of improved effectiveness compared with standard of care comes
      at a cost. How can we be sure that personalized medicine indeed provides a
      measurable clinical benefit, that we will be able to afford it, and that we can
      provide adequate access? The risk-benefit evaluation that accompanies each
      medical decision requires not only good clinical data but also an assessment of
      cost and infrastructure needed to provide access to technology. Several examples
      from the last decade illustrate which types of personalized medicines and
      diagnostic tests are easily being taken up in clinical practice and which types
      are more difficult to introduce. And as regulators and payers in the United
      States and elsewhere are taking on personalized medicine, an interesting
      convergence can be observed: better, more complete information for both approval
      and coverage decisions could be gained from a coordination of regulatory and
      reimbursement questions. Health economics and outcomes research (HEOR) emerges as
      an approach that can satisfy both needs. Although HEOR represents a well
      established approach to demonstrate the effectiveness of interventions in many
      areas of medical practice, few HEOR studies exist in the field of personalized
      medicine today. It is reasonable to expect that this will change over the next
      few years. 

PMID- 24034311
TI  - Economic incentives for evidence generation: promoting an efficient path to
      personalized medicine.
AB  - The preceding articles in this volume have identified and discussed a wide range
      of methodological and practical issues in the development of personalized
      medicine. This concluding article uses the resulting insights to identify
      implications for the economic incentives for evidence generation. It argues that
      promoting an efficient path to personalized medicine is going to require
      appropriate incentives for evidence generation including: 1) a greater
      willingness on the part of payers to accept prices that reflect value; 2)
      consideration of some form of intellectual property protection (e.g., data
      exclusivity) for diagnostics to incentivize generation of evidence of clinical
      utility; 3) realistic expectations around the standards for evidence; and 4)
      public investment in evidence collection to complement the efforts of payers and
      manufacturers. It concludes that such incentives could build and maintain a
      balance among: 1) realistic thresholds for evidence and the need for payers to
      have confidence in the clinical utility of the drugs and tests they use; 2)
      payment for value, with prices that ensure cost-effectiveness for health systems;
      and 3) levels of intellectual property protection for evidence generation that
      provide a return for those financing research and development, while encouraging
      competition to produce both better and more efficient tests. 

PMID- 24034312
TI  - The faces of personalized medicine: a framework for understanding its meaning and
      scope.
AB  - The objective of this article was to provide a framework for understanding the
      different definitions of the term "personalized medicine." The term personalized
      medicine is used regularly but interpreted in different ways. This article
      approaches the term by starting with a broad view of clinical medicine, where
      three components can be distinguished: the questions (e.g., what is the
      diagnosis?), the methods used to answer them (e.g., a test), and the available
      actions (e.g., to give or not give a particular drug). Existing definitions of
      personalized medicine disagree about which questions, methods, and actions fall
      within its domain. Some define the term narrowly, referring to the use of a
      diagnostic test to predict drug response, thereby clarifying whether or not a
      patient will benefit from that drug. An example of this combination is the
      HER2/neu test to predict the effectiveness of trastuzumab in breast cancer. Many
      who adopt this definition associate the concept of personalized medicine with
      fields such as genetics, genomics, and other types of "-omics." In contrast,
      others view personalized medicine as a concept that has always existed, because
      medicine has always considered the needs of the individual. One definition of
      personalized medicine that accommodates both interpretations is "the use of
      combined knowledge (genetic or otherwise) about a person to predict disease
      susceptibility, disease prognosis, or treatment response and thereby improve that
      person's health." This predictive ability can increase over time through
      innovations in various technologies, resulting in further improvements in health
      outcomes. Moreover, these developments can lead to a better understanding of the
      underlying causes of disease, which can eventually lead to breakthroughs in the
      treatment of individual patients. In that sense, a truly personalized form of
      medicine can also be seen as an ideal, a goal that will be achieved only after
      multiple advances in science. Although the term personalized medicine was
      rechristened somewhat recently, our ability to personalize medicine will continue
      to advance in unimaginable ways as we come to learn more about the heterogeneity
      that exists among individuals and diseases. 

PMID- 24034313
TI  - Computational prediction of RNA secondary structure.
AB  - The purpose of this section is to detail methods for the computational prediction
      of RNA secondary structure. This protocol is intended to provide an easy entry
      into the field of RNA structure prediction for those wishing to utilize it in
      their research and to suggest 'best practices' for going from sequence to
      secondary structure depending on the available data. 

PMID- 24034314
TI  - Reverse-transcription PCR (RT-PCR).
AB  - RT-PCR is commonly used to test for genetic diseases and to characterize gene
      expression in various tissue types, cell types, and over developmental time
      courses. This serves as a form of expression profiling, but typically as a
      candidate approach. RT-PCR is also commonly used to clone cDNAs for further use
      with other molecular biology techniques (e.g., see Oligo(dT)-primed RT-PCR
      isolation of polyadenylated RNA degradation intermediates and Circularized RT-PCR
      (cRT-PCR): analysis of RNA 5' ends, 3' ends, and poly(A) tails). 

PMID- 24034315
TI  - Northern blotting.
AB  - To measure the size and amount of RNA transcribed from a specific gene of
      interest. 

PMID- 24034316
TI  - Explanatory chapter: nuclease protection assays.
AB  - Nuclease protection assays are a highly sensitive, solution-based technique used
      to detect and quantify specific RNA targets from complex RNA mixtures. Today,
      this technique is frequently performed using kits, and the following chapter will
      explain the principles of how these kits work and some considerations to keep in
      mind when using them. 

PMID- 24034317
TI  - In vitro transcription from plasmid or PCR-amplified DNA.
AB  - This protocol describes the synthesis and purification of RNAs using plasmid DNA
      or PCR-amplified DNA as a template. This procedure should give NTP-free, full
      length RNA for all sizes of RNA. This protocol is derived from Milligan and
      Uhlenbeck, the classic paper on T7 transcription reactions, with modifications. 

PMID- 24034318
TI  - Measurement of in vivo RNA synthesis rates.
AB  - A technique is described to directly measure ongoing transcription from
      individual genes in permeabilized cells of either the budding yeast Saccharomyces
      cerevisiae or the fission yeast Schizosaccharomyces pombe. Transcription run-on
      (TRO) analysis is used to compare the relative rates of synthesis for specific
      transcripts in cells grown under different environmental conditions or harvested
      at different stages of development. As the amount of an individual RNA species
      present at any given time is determined by its net rate of synthesis and
      degradation, an accurate picture of transcription per se can be obtained only by
      directly measuring de novo synthesis of RNA (if you are interested in RNA
      degradation, see Method for measuring mRNA decay rate in Saccharomyces
      cerevisiae). Most techniques employed to measure changes in the relative levels
      of individual transcripts present under different conditions, including Northern
      analysis (see Northern blotting), RT-PCR (see Reverse-transcription PCR (RT
      PCR)), nuclease protection assays (see Explanatory Chapter: Nuclease Protection
      Assays), and genome-wide assays, such as microarray analysis and high throughput
      RNA sequencing, measure changes in the steady-state level of a transcript, which
      may or may not reflect the actual changes in transcription of the gene. Recent
      studies carried out in fission yeast have demonstrated that increases in the
      steady-state level (accumulation) of many individual mRNAs occur without any
      significant changes in transcription rates (McPheeters et al., 2009),
      highlighting the important role of regulated RNA stability in determining gene
      expression programs (Harigaya et al., 2006). 

PMID- 24034319
TI  - Method for measuring mRNA decay rate in Saccharomyces cerevisiae.
AB  - Eukaryotic mRNA degradation is an essential aspect of gene regulation. Properly
      turning off transcript generation ensures that protein synthesis does not occur
      indefinitely. By ensuring that all mRNAs are destroyed, cells can adapt quickly
      to changing physiological and environmental conditions. Eukaryotic cytoplasmic
      mRNA degradation is predominately initiated by removal of the poly(A) tail at the
      3' end (deadenylation). Following deadenylation, either the mRNA is degraded in a
      3'-5' manner or the cap is removed and the mRNA is degraded 5'-3' (reviewed in
      Coller and Parker, 2004). Determining mRNA decay rates, as indicated by mRNA half
      life, is vital to understand how mRNA stability is modulated under various
      physiological conditions. 

PMID- 24034320
TI  - Analysis of polysomes from bacteria.
AB  - In actively growing cells, the rate of translation initiation is relatively
      rapid. As a result, multiple ribosomes simultaneously engaged in translation
      become spaced along single mRNA molecules. These structures, termed polysomes,
      can be separated from ribosomal subunits and single ribosomes because they
      migrate faster through sucrose gradients (Noll, 2008). In fact, polysomes
      containing various numbers of ribosomes can be resolved from one another since
      each ribosome adds substantial mass. It is straightforward to prepare bacterial
      lysates and resolve all the ribosomal fractions using sucrose gradient
      sedimentation. The resulting polysome 'profile' can provide a sort of snapshot of
      the translation activity in the cell. Polysome analysis has been used to study
      the effects of mutations and/or growth conditions on translation and to address
      whether particular cellular components are associated with the translational
      machinery (Powers and Noller, 1990; Gregory et al., 1994; Moine and Dahlberg,
      1994; Firpo et al., 1996; Fredrick et al., 2000; Ataide et al., 2009; Melamed et
      al., 2009; Saini et al., 2009). In combination with other techniques, polysome
      analysis has been used to deduce rate constants for certain phases of translation
      (e.g., initiation, elongation, termination) (Arava et al., 2003; 2005). Finally,
      use of purified polysomes in biochemical experiments has been instrumental for
      the isolation and characterization of translation factors such as ribosome
      recycling factor (RRF) (Hirashima and Kaji, 1972; Fujiwara et al., 2001; Hirokawa
      et al., 2002; Ito et al., 2002). Here, we describe a simple and convenient method
      of preparing and analyzing polysomes from Escherichia coli, which should be
      generally applicable to many bacteria. We also discuss parameters that influence
      the ribosome density on mRNA, which should be kept in mind when polysome profiles
      are being interpreted. 

PMID- 24034321
TI  - Polysome profile analysis--yeast.
AB  - More than one 80S monosome can translate an mRNA molecule at a time producing
      polysomes. The most widely used method to separate 40S and 60S ribosomal subunits
      from 80S monosomes and polysomes is a high-velocity centrifugation of whole cell
      extracts in linear sucrose gradients. This polysome profile analysis technique
      has been routinely used to monitor translational fitness of cells under a variety
      of physiological conditions, to investigate functions of initiation factors
      involved in translation, to reveal defects in ribosome biogenesis, to determine
      roles of 5' UTR structures on mRNA translatability, and more recently for
      examination of miRNA-mediated translational repression (see an application of
      this protocol on Polysome analysis for determining mRNA and ribosome association
      in Saccharomyces cerevisiae). 

PMID- 24034322
TI  - Polysome analysis of mammalian cells.
AB  - To assess the global translational level of mammalian cells (see similar
      protocols for bacteria and yeast on Analysis of polysomes from bacteria, Polysome
      Profile Analysis - Yeast and Polysome analysis for determining mRNA and ribosome
      association in Saccharomyces cerevisiae). 

PMID- 24034323
TI  - Polysome analysis for determining mRNA and ribosome association in Saccharomyces
      cerevisiae.
AB  - The control of mRNA translation is vital for gene expression and it is regulated
      under various physiological and pathological conditions (Groppo and Richter,
      2009). For example, under some physiological conditions, translational initiation
      is impaired. Therefore, the association of mRNA with ribosomes and/or ribosomal
      subunits can provide a powerful means to dissect specific aspects of
      posttranscriptional mRNA regulation. This protocol describes a technique used to
      determine ribosome occupancy on mRNA. 

PMID- 24034324
TI  - Oligo(dT)-primed RT-PCR isolation of polyadenylated RNA degradation
      intermediates.
AB  - The posttranscriptional modification of RNA by polyadenylation serves various
      purposes, among them to assist in RNA degradation (see an alternative protocol
      for measuring RNA degradation on Method for measuring mRNA decay rate in
      Saccharomyces cerevisiae). This function, once thought to occur in prokaryotic or
      organellar systems alone, is now known to operate in the nuclei and cytoplasm of
      eukaryotes as well (Slomovic et al., 2008; Slomovic et al., 2010; Houseley and
      Tollervey, 2009; Deutscher, 2006). Poly(A)-assisted RNA decay begins with the
      endonucleolytic cleavage of the transcript. Following this, a poly(A) or oligo(A)
      tail is added to the 3' end of the cleavage product. This tag serves as a
      'landing pad' for 3'-5' exoribonucleases that then begin to digest the RNA
      fragment. Truncated RNA molecules that have undergone tail addition but have yet
      to be degraded are called degradation intermediates. The detection of such
      intermediates is considered a tell-tale sign that poly(A)-assisted RNA decay
      occurs in the organism being studied. Determination of the tail nucleotide
      composition by DNA sequencing often aids the researcher in identifying the enzyme
      responsible for tail synthesis since tails can be either homopolymeric
      (exclusively A residues) or heteropolymeric (A-rich tails that may include other
      nucleotides). The following protocol, based on oligo(dT)-primed reverse
      transcription, describes the step-by-step detection and isolation of adenylated
      degradation intermediates in the study of poly(A)-assisted RNA decay. 

PMID- 24034326
TI  - RNA radiolabeling.
AB  - Radioactive end-labeling is useful for visualizing and allowing the detection of
      nucleic acids at trace concentrations. Radioactive end-labeling can be carried
      out on RNA, DNA, or other modified nucleic acids. For RNA, the uses of end
      labeling extend beyond simple detection of the intact RNA. A number of RNA
      molecules studied by biologists form three-dimensional structures in solution,
      and many of the techniques used to study these structures depend on the ability
      to visualize the RNA after fragmentation. Labeling at either the 5'- or 3'-end
      serves as a gateway into these structural analysis techniques (see Structural
      Analysis of RNA Backbone Using In-Line Probing), and protocols for these labeling
      procedures are described below (for a nonradiactive labeling protocol, see
      Fluorescently Labeling Synthetic RNAs). 

PMID- 24034325
TI  - Circularized RT-PCR (cRT-PCR): analysis of the 5' ends, 3' ends, and poly(A)
      tails of RNA.
AB  - Many techniques that are used to characterize individual RNA molecules can
      potentially alter the original transcript sequence or its posttranscriptional
      modifications, such as polyadenylation. Methods that are designed to define the
      ends of an RNA molecule, for example, oligonucleotide ligation, avoid altering
      the transcript sequence but can usually fulfill only one objective per experiment
      (e.g., define the 5' or the 3' end). In contrast, not only does circularized
      reverse transcription coupled with PCR (cRT-PCR) preserve the original 5' and 3'
      ends of the transcript and posttranscriptionally added extensions, but also the
      material from one experimental procedure can be utilized in order to characterize
      both the 5' and 3' ends. Furthermore, if suitable oligonucleotide primers are
      designed, cRT-PCR can be used to isolate truncated, adenylated (and
      nonadenylated) molecules that are intermediates in RNA decay (Slomovic and
      Schuster, 2008). 

PMID- 24034327
TI  - Fluorescently labeling synthetic RNAs.
AB  - This protocol covers the steps required to incorporate N-hydroxysuccinamide (NHS)
      functionalized fluorophores into synthetic RNAs containing a residue derivatized
      with a primary amine. This method has been widely used to label RNA
      oligonucleotides that are used directly, targeted to a complementary RNA using
      base pairing rules, or covalently ligated to a RNA of interest (Ha et al., 1999;
      Hodak et al., 2005; Baum and Silverman, 2007; Sattint et al., 2008; Akiyama and
      Stone, 2009; Solomatin and Herschlag, 2009). While this technique is quite
      general, the details of a particular experiment can vary, therefore, it is always
      important to keep in mind that other labeling strategies are available and should
      potentially be considered. 

PMID- 24034328
TI  - Analysis of RNA by analytical polyacrylamide gel electrophoresis.
AB  - Polyacrylamide gel electrophoresis (PAGE) is a powerful tool for analyzing RNA
      samples. Denaturing PAGE provides information on the sample composition and
      structural integrity of the individual RNA species. Nondenaturing gel
      electrophoresis allows separation of the conformers and alternatively folded RNA
      species. It also can be used to resolve RNA protein complexes and to detect RNA
      complex formation by analyzing changes in the electrophoretic mobility of the
      RNA. RNA can be visualized within gels by different methods depending on the
      nature of the detection reagent. RNA molecules can be stained with various dyes,
      including toluidine blue, SYBR green, and ethidium bromide. Radioactively labeled
      RNA molecules are visualized by autoradiography, and fluorescently labeled RNA
      molecules can be observed with a fluorescence scanner. Generally, gels between
      0.4 and 1.5mm thick are used for analytical PAGE. Gels thinner than 1mm are
      fragile and thus usually are not stained but rather are used for radiolabeled
      RNA. The gels are dried and the radiolabeled RNA is visualized by
      autoradiography. 

PMID- 24034330
TI  - Explanatory chapter: nucleic acid concentration determination.
AB  - This protocol describes a method for determining the concentration of a nucleic
      acid sample. 

PMID- 24034329
TI  - RNA purification by preparative polyacrylamide gel electrophoresis.
AB  - Preparative polyacrylamide gel electrophoresis (PAGE) is a powerful tool for
      purifying RNA samples. Denaturing PAGE allows separation of nucleic acids that
      differ by a single nucleotide in length. It is commonly used to separate and
      purify RNA species after in vitro transcription, to purify naturally occurring
      RNA variants such as tRNAs, to remove degradation products, and to purify labeled
      RNA species. To preserve RNA integrity following purification, RNA is usually
      visualized by UV shadowing or stained with ethidium bromide or SYBR green dyes. 

PMID- 24034331
TI  - RNA purification--precipitation methods.
AB  - When working with RNA, the need often arises to concentrate a sample or purify it
      from various salts, nucleotides, and proteins. RNA precipitation is an easy and
      cost-effective method for the concentration of RNA, leaving a pellet that can be
      resuspended in the buffer of choice. 

PMID- 24034332
TI  - Reverse transcriptase dideoxy sequencing of RNA.
AB  - During the course of studying the structure and function of RNA molecules and the
      proteins that they may encode, as well as studies of the expression of a given
      gene, there often arises a need to learn the nucleotide sequence of an RNA
      molecule. While the sequence of a particular RNA is ordinarily encompassed within
      a corresponding DNA sequence, RNA sequencing lends the advantage of giving the
      transcription initiation and termination sequences, and the sites where
      modifications from the original DNA sequence occur. 

PMID- 24034333
TI  - RNA structure experimental analysis--chemical modification.
AB  - The purpose of this protocol is to identify 'footprints' of protein on RNA.
      However, it can also be used to analyze the secondary structure of RNA. This
      protocol is optimized for large RNA molecules; however, it can be adapted for the
      study of small RNAs. 

PMID- 24034334
TI  - Structural analysis of RNA backbone using in-line probing.
AB  - To determine the secondary structure characteristics of nucleotides in an RNA
      polymer. 

PMID- 24034335
TI  - Methods in Enzymology. Laboratory methods in enzymology: RNA. Preface.

PMID- 24034336
TI  - Self-reported quality of life in a Scottish first-episode psychosis cohort:
      associations with symptomatology and premorbid adjustment.
AB  - BACKGROUND: There is increased interest in quality of life (QoL) as a clinically
      relevant factor in adjustment to, and recovery from, first-episode psychosis
      (FEP). Given the subjective nature of QoL, it is proposed that this variable may
      be associated with compromised functioning prior to the onset of psychosis, and
      may also have an impact on an individual's adjustment to psychosis after
      treatment is initiated. AIM: The current study aims to explore associations
      between subjective QoL, symptomatology, premorbid adjustment, duration of
      untreated psychosis (DUP) and engagement with services after onset of treatment.
      METHOD: A cross-sectional cohort of Scottish individuals undergoing treatment for
      FEP were characterized in terms of psychotic symptomatology, premorbid
      adjustment, DUP and service engagement. Self-reported QoL was measured using the
      World Health Organization Quality of Life Brief Scale, allowing for the
      measurement of physical, psychological, social relational and environmental
      aspects of QoL. RESULTS: Higher scores for subjective QoL components were
      associated with better premorbid adjustment, lower positive psychotic symptoms,
      lower negative symptoms and less cognitive disorganization. Childhood premorbid
      adjustment predicted both physical and social relationship QoL. DISCUSSION:
      Subjective QoL domains differ in their associations with clinical and premorbid
      factors. The relationship between premorbid adjustment and QoL requires further
      exploration in FEP.

PMID- 24034337
TI  - Characterization of a purine permease family gene OsPUP7 involved in growth and
      development control in rice.
AB  - In this study, PUP-type cytokinin transporter genes were identified in rice
      (Oryza sativa L.). The Oryza sativa purine permease (OsPUP) family has 12 members
      that show similar predicted protein sequences with AtPUPs. To reveal the
      functions of OsPUP genes, we searched the T-DNA mutant library of rice and found
      one mutant for the member OsPUP7. The T-DNA insertion caused a new transcript
      that encodes a protein with 26 amino acids different from the native OsPUP7 at
      the C-terminus. The mutant showed multiple phenotypic changes including increased
      plant height, big seeds, and delayed flowering. The mutant also showed increased
      sensitivity to drought and salt stresses and treatments with kinetin and abscisic
      acid. OsPUP7 is expressed mainly in the vascular bundle, pistil, and stamens. The
      measurement of cytokinins (CKs) showed that CK content in the mutant spikelets
      accumulated higher than that in the wild type. Moreover, uptake experiment in the
      yeast fcy2 mutant suggested that OsPUP7 has the ability to transport caffeine, a
      CK derivative. Our results indicate that the PUP transport system also exists in
      rice, and OsPUP7 has an important role in the transport of CK, thus affecting
      developmental process and stress responses. 

PMID- 24034338
TI  - Elderly age is not a negative predictive factor for virological response to
      therapy with pegylated interferon-alpha and ribavirin in chronic hepatitis C
      virus patients.
AB  - BACKGROUND & AIMS: Age is frequently discussed as negative host factor to achieve
      a sustained virological response (SVR) to antiviral therapy of chronic hepatitis
      C. However, elderly patients often show advanced fibrosis/cirrhosis as known
      negative predictive factor. The aim of this study was to assess age as an
      independent predictive factor during antiviral therapy. METHODS: Overall, 516
      hepatitis C patients were treated with pegylated interferon-alpha and ribavirin,
      thereof 66 patients >=60 years. We analysed the impact of host factors (age,
      gender, fibrosis, haemoglobin, previous hepatitis C treatment) and viral factors
      (genotype, viral load) on SVR per therapy course by performing a generalized
      estimating equations (GEE) regression modelling, a matched pair analysis and a
      classification tree analysis. RESULTS: Overall, SVR per therapy course was 42.9
      and 26.1%, respectively, in young and elderly patients with hepatitis C virus
      (HCV) genotypes 1/4/6. The corresponding figures for HCV genotypes 2/3 were 74.4
      and 84%. In the GEE model, age had no significant influence on achieving SVR. In
      matched pair analysis, SVR was not different in young and elderly patients (54.2
      and 55.9% respectively; P = 0.795 in binominal test). In classification tree
      analysis, age was not a relevant splitting variable. CONCLUSIONS: Age is not a
      significant predictive factor for achieving SVR, when relevant confounders are
      taken into account. As life expectancy in Western Europe at age 60 is more than
      20 years, it is reasonable to treat chronic hepatitis C in selected elderly
      patients with relevant fibrosis or cirrhosis but without major concomitant
      diseases, as SVR improves survival and reduces carcinogenesis.

PMID- 24034339
TI  - Metabolic engineering of beta-carotene in orange fruit increases its in vivo
      antioxidant properties.
AB  - Orange is a major crop and an important source of health-promoting bioactive
      compounds. Increasing the levels of specific antioxidants in orange fruit through
      metabolic engineering could strengthen the fruit's health benefits. In this work,
      we have afforded enhancing the beta-carotene content of orange fruit through
      blocking by RNA interference the expression of an endogenous beta-carotene
      hydroxylase gene (Csbeta-CHX) that is involved in the conversion of beta-carotene
      into xanthophylls. Additionally, we have simultaneously overexpressed a key
      regulator gene of flowering transition, the FLOWERING LOCUS T from sweet orange
      (CsFT), in the transgenic juvenile plants, which allowed us to obtain fruit in an
      extremely short period of time. Silencing the Csbeta-CHX gene resulted in oranges
      with a deep yellow ('golden') phenotype and significant increases (up to 36-fold)
      in beta-carotene content in the pulp. The capacity of beta-carotene-enriched
      oranges for protection against oxidative stress in vivo was assessed using
      Caenorhabditis elegans as experimental animal model. Golden oranges induced a 20%
      higher antioxidant effect than the isogenic control. This is the first example of
      the successful metabolic engineering of the beta-carotene content (or the content
      of any other phytonutrient) in oranges and demonstrates the potential of genetic
      engineering for the nutritional enhancement of fruit tree crops. 

PMID- 24034340
TI  - Tobacco control in patients treated for chronic pain: a survey of pain fellowship
      program directors.
AB  - BACKGROUND AND OBJECTIVES: Previous studies have established the relationship
      between tobacco use and pain severity among patients suffering from chronic pain.
      Unfortunately, many physicians feel underprepared to counsel patients on smoking
      cessation. The purpose of this study was to identify the attitudes, beliefs, and
      practices of pain medicine fellowship directors in regard to tobacco control
      interventions and trainee education. METHODS: Program directors of ACGME
      accredited pain medicine fellowships were surveyed via a web-based form to assess
      current practices in tobacco intervention and to gauge interest in incorporating
      tobacco control into their current fellowship training curriculum. RESULTS: Of
      the respondents, the majority indicated that they frequently asking their
      patients about tobacco use and advise them to quit. In addition, most agreed that
      presenting tobacco control is a responsibility of pain physicians. However, few
      consistently provided any assistance with quitting. Finally, the majority of
      program directors felt that pain medicine fellowships should include tobacco
      control training and were interested in incorporating an educational module about
      smoking and pain into their training program. CONCLUSIONS: This survey of pain
      medicine fellowship program directors indicates that although smoking cessation
      interventions are not being consistently applied in academic pain practices,
      there is a strong interest in doing so. Furthermore, the majority of program
      directors recognized the importance of incorporating tobacco control training
      into pain medicine fellowships. This recognition may provide an opportunity to
      develop a web-based training module that could be easily incorporated into the
      upcoming milestones in pain medicine training.

PMID- 24034341
TI  - Characteristics of lipid micro- and nanoparticles based on supercritical
      formation for potential pharmaceutical application.
AB  - The interest of the pharmaceutical industry in lipid drug delivery systems due to
      their prolonged release profile, biocompatibility, reduction of side effects, and
      so on is already known. However, conventional methods of preparation of these
      structures for their use and production in the pharmaceutical industry are
      difficult since these methods are usually multi-step and involve high amount of
      organic solvent. Furthermore, some processes need extreme conditions, which can
      lead to an increase of heterogeneity of particle size and degradation of the
      drug. An alternative for drug delivery system production is the utilization of
      supercritical fluid technique. Lipid particles produced by supercritical fluid
      have shown different physicochemical properties in comparison to lipid particles
      produced by classical methods. Such particles have shown more physical stability
      and narrower size distribution. So, in this paper, a critical overview of
      supercritical fluid-based processes for the production of lipid micro- and
      nanoparticles is given and the most important characteristics of each process are
      highlighted. 

PMID- 24034342
TI  - U.S. Centers for Disease Control and Prevention launches new chronic kidney
      disease surveillance system website.
AB  - The burden of chronic kidney disease (CKD) is substantial and is associated with
      poor health outcomes including increase hospitalizations and premature deaths, as
      well as considerable health care cost. In recognition of this mounting public
      health problem, the U.S. Centers for Disease Control and Prevention and their
      collaborators created a national CKD surveillance system. This commentary
      introduces the national CKD surveillance system and discusses some of its
      potential uses. 

PMID- 24034343
TI  - TRPV4-mediated calcium influx and ciliary activity in human native airway
      epithelial cells.
AB  - The transient receptor potential vanilloid 4 (TRPV4) is a calcium permeable ion
      channel expressed in airway epithelial cells. Based on studies of cell lines and
      animals, TRPV4 has been suggested to play a role in the regulation of ciliary
      beat frequency (CBF). Whether the same is true for human ciliated epithelial
      cells is not known. Therefore, the aim was to examine the expression and function
      of TRPV4 in human native nasal epithelial cells. Expression of TRPV4 mRNA in
      nasal epithelial cells and in the cell lines BEAS2B and 16HBE was confirmed by
      quantitative real-time PCR. A marked apical TRPV4 immunoreactivity was observed
      in nasal epithelial cells using immunocytochemistry. Responses to pharmacological
      modulation of TRPV4 were assessed with calcium imaging and CBF measurements. The
      TRPV4 agonist GSK1016790A produced concentration-dependent calcium responses in
      TRPV4-expressing HEK293, BEAS2B and 16HBE cells, and the TRPV4 antagonist
      HC067047 caused a rightward shift of the GSK1016790A concentration-response
      curves. Nasal epithelial cells responded to the TRPV4 agonist GSK1016790A with
      increased intracellular calcium signals and increased CBF, followed by cessation
      of ciliary beating and cell death. These effects were prevented or inhibited by
      the TRPV4 antagonist HC067047, the TRP channel blocker ruthenium red or removal
      of extracellular calcium. We conclude that TRPV4 is expressed in human primary
      nasal epithelial cells and modulates epithelial calcium levels and CBF. Thus,
      TRPV4 may participate in mucociliary clearance and airway protection. However,
      exaggerated activation of TRPV4 may result in epithelial cell death. 

PMID- 24034344
TI  - Interleukin-1 beta and tumor necrosis factor alpha inhibit migration activity of
      chondrogenic progenitor cells from non-fibrillated osteoarthritic cartilage.
AB  - INTRODUCTION: The repair capability of traumatized articular cartilage is highly
      limited so that joint injuries often lead to osteoarthritis. Migratory
      chondrogenic progenitor cells (CPC) might represent a target cell population for
      in situ regeneration. This study aims to clarify, whether 1) CPC are present in
      regions of macroscopically intact cartilage from human osteoarthritic joints, 2)
      CPC migration is stimulated by single growth factors and the cocktail of factors
      released from traumatized cartilage and 3) CPC migration is influenced by
      cytokines present in traumatized joints. METHODS: We characterized the cells
      growing out from macroscopically intact human osteoarthritic cartilage using a
      panel of positive and negative surface markers and analyzed their differentiation
      capacity. The migratory response to platelet-derived growth factor (PDGF)-BB,
      insulin-like growth factor 1 (IGF-1), supernatants obtained from in vitro
      traumatized cartilage and interleukin-1 beta (IL-1beta) as well as tumor necrosis
      factor alpha (TNF-alpha) were tested with a modified Boyden chamber assay. The
      influence of IL-1beta and TNF-alpha was additionally examined by scratch assays
      and outgrowth experiments. RESULTS: A comparison of 25 quadruplicate marker
      combinations in CPC and bone-marrow derived mesenchymal stromal cells showed a
      similar expression profile. CPC cultures had the potential for adipogenic,
      osteogenic and chondrogenic differentiation. PDGF-BB and IGF-1, such as the
      supernatant from traumatized cartilage, induced a significant site-directed
      migratory response. IL-1beta and TNF-alpha significantly reduced basal cell
      migration and abrogated the stimulative effect of the growth factors and the
      trauma supernatant. Both cytokines also inhibited cell migration in the scratch
      assay and primary outgrowth of CPC from cartilage tissue. In contrast, the
      cytokine IL-6, which is present in trauma supernatant, did not affect growth
      factor induced migration of CPC. CONCLUSION: These results indicate that
      traumatized cartilage releases chemoattractive factors for CPC but IL-1beta and
      TNF-alpha inhibit their migratory activity which might contribute to the low
      regenerative potential of cartilage in vivo.

PMID- 24034346
TI  - Nocturia among elderly men living in a rural area in Egypt, and its impact on
      sleep quality and health-related quality of life.
AB  - AIM: Nocturia is such a commonplace occurrence in the lives of many older adults
      that it is frequently overlooked as a potential cause of sleep disturbance. The
      aim of the present study was to evaluate the prevalence of nocturia among elderly
      men living in a rural area in Egypt, and its impact on sleep quality and health
      related quality of life (HRQoL). METHOD: This was a cross-sectional study. A
      total of 1200 elderly men participated in the survey. The Pittsburgh Sleep
      Quality Index (PSQI) Arabic version and the short form-36 (SF-36) were used in
      this survey. RESULTS: The prevalence of nocturia in the studied participants (>=
      1 void/night) was 63.5%. With the criterion (>= 2 voids/night) the prevalence was
      46.0%. Multivariate logistic regression analysis showed that nocturia is an
      independent risk factor of poor sleep quality (OR 5.08), and poor sleep is an
      independent risk factor of the poor physical component of QoL (OR 17.6) and the
      mental component of QoL (OR 3.2). CONCLUSION: Nocturia is widely prevalent among
      elderly men living in a rural area in Egypt. The adverse effect of nocturia on
      QoL is related to poor sleep.

PMID- 24034345
TI  - Probiotic milk consumption in pregnancy and infancy and subsequent childhood
      allergic diseases.
AB  - BACKGROUND: Whether probiotics, which can influence the microbiome, prevent
      infant eczema or allergic disease remains an open question. Most studies have
      focused on high-risk infants. OBJECTIVES: We sought to assess whether consumption
      of probiotic milk products protects against atopic eczema, rhinoconjunctivitis,
      and asthma in early childhood in a large population-based pregnancy cohort (the
      Norwegian Mother and Child Cohort study). METHODS: We examined associations
      between consumption of probiotic milk products in pregnancy and infancy with
      questionnaire-reported atopic eczema, rhinoconjunctivitis, and asthma in 40,614
      children. Relative risks (RRs) were calculated by using general linear models
      adjusted for potential confounders. RESULTS: Consumption of probiotic milk in
      pregnancy was associated with a slightly reduced relative risk (RR) of atopic
      eczema at 6 months (adjusted RR, 0.94; 95% CI, 0.89-0.99) and of
      rhinoconjunctivitis between 18 and 36 months (adjusted RR, 0.87; 95% CI, 0.78
      0.98) compared with no consumption during pregnancy. Maternal history of allergic
      disease did not notably influence the associations. When both the mother (during
      pregnancy) and infant (after 6 months of age) had consumed probiotic milk, the
      adjusted RR of rhinoconjunctivitis was 0.80 (95% CI, 0.68-0.93) relative to no
      consumption by either. Probiotic milk consumption was not associated with asthma
      at 36 months. CONCLUSIONS: In this population-based cohort consumption of
      probiotic milk products was related to a reduced incidence of atopic eczema and
      rhinoconjunctivitis, but no association was seen for incidence of asthma by 36
      months of age.

PMID- 24034347
TI  - Global insights into energetic and metabolic networks in Rhodobacter sphaeroides.
AB  - BACKGROUND: Improving our understanding of processes at the core of cellular
      lifestyles can be aided by combining information from genetic analyses, high
      throughput experiments and computational predictions. RESULTS: We combined data
      and predictions derived from phenotypic, physiological, genetic and computational
      analyses to dissect the metabolic and energetic networks of the facultative
      photosynthetic bacterium Rhodobacter sphaeroides. We focused our analysis on
      pathways crucial to the production and recycling of pyridine nucleotides during
      aerobic respiratory and anaerobic photosynthetic growth in the presence of an
      organic electron donor. In particular, we assessed the requirement for NADH/NADPH
      transhydrogenase enzyme, PntAB during respiratory and photosynthetic growth.
      Using high-throughput phenotype microarrays (PMs), we found that PntAB is
      essential for photosynthetic growth in the presence of many organic electron
      donors, particularly those predicted to require its activity to produce NADPH.
      Utilizing the genome-scale metabolic model iRsp1095, we predicted alternative
      routes of NADPH synthesis and used gene expression analyses to show that
      transcripts from a subset of the corresponding genes were conditionally increased
      in a DeltapntAB mutant. We then used a combination of metabolic flux predictions
      and mutational analysis to identify flux redistribution patterns utilized in the
      DeltapntAB mutant to compensate for the loss of this enzyme. Data generated from
      metabolic and phenotypic analyses of wild type and mutant cells were used to
      develop iRsp1140, an expanded genome-scale metabolic reconstruction for R.
      sphaeroides with improved ability to analyze and predict pathways associated with
      photosynthesis and other metabolic processes. CONCLUSIONS: These analyses
      increased our understanding of key aspects of the photosynthetic lifestyle,
      highlighting the added importance of NADPH production under these conditions. It
      also led to a significant improvement in the predictive capabilities of a
      metabolic model for the different energetic lifestyles of a facultative organism.

PMID- 24034348
TI  - The tRNA 3'-end processing enzyme tRNase Z2 contributes to chloroplast biogenesis
      in rice.
AB  - tRNase Z (TRZ) is a ubiquitous endonuclease that removes the 3'-trailer from
      precursor tRNAs during maturation. In yeast and animals, TRZ regulates the cell
      cycle via its (t)RNA processing activity; however, its physiological function in
      higher plants has not been well characterized. This study describes the
      identification of a rice (Oryza sativa) TRZ2 mutant; plants homozygous for the
      osatrz2 mutation were albinos with deficient chlorophyll content. A microscopic
      analysis of the mutant plants revealed that the transition of proplastids to
      chloroplasts was arrested at an early stage, and the number and size of the
      plastids in callus cells was substantially decreased. A genetic complementation
      test and an RNA interference analysis confirmed that disruption of OsaTRZ2 was
      responsible for the mutant phenotype. OsaTRZ2 is expressed in all rice tissues,
      but is preferentially expressed in leaves, sheathes, and calli. OsaTRZ2 was
      subcellularly localized in chloroplasts, and displayed tRNA 3'-end processing
      activity in both in vitro and in vivo assays. In the osatrz2 mutants,
      transcription of plastid-encoded and nucleus-encoded RNA polymerases was severely
      reduced and moderately increased, respectively. These results suggest that the
      tRNA 3' processing activity of OsaTRZ2 contributes to chloroplast biogenesis. 

PMID- 24034349
TI  - New venues for the treatment of hepatitis: pharmacological or genetical
      interventions of macrophage polarization by targeting Ang/Tie-2 axis.

PMID- 24034350
TI  - Emergence of well differentiated neuroendocrine (carcinoid) tumours following
      chemoradiotherapy for rectal adenocarcinoma.

PMID- 24034351
TI  - Detection of Toxoplasma gondii in the milk of naturally infected goats in the
      Northeast of Brazil.
AB  - The aim of the present study was to detect the genomic DNA of Toxoplasma gondii
      in milk samples from naturally infected goats in the state of Pernambuco,
      (Brazil). In total, 248 blood serum samples were collected and processed from
      lactating goats and then submitted to a search for antibodies to T. gondii
      through the indirect immunofluorescence reaction. Samples with a score of 64 or
      more were considered positive. In total, 248 milk samples were collected and
      processed from the same group of goats in order to study the DNA of T. gondii
      using the polymerase chain reaction (PCR) technique. In the serum samples, 56/248
      (22.58%) of the animals were positive, whereas the DNA of the parasite was
      detected in 15/248 (6.05%) of the milk samples. Five of these 15 samples were
      animals who were also positive in the serology. This study reports the first
      occurrence of the elimination of T. gondii from the milk of naturally infected
      goats in the north-east of Brazil. It is suggested that the consumption of in
      natura goat milk may constitute a potential risk to the health of milk consumers
      in this region.

PMID- 24034352
TI  - Sleep duration and adiposity in older adolescents from Otago, New Zealand:
      relationships differ between boys and girls and are independent of food choice.
AB  - BACKGROUND: While relationships between sleep and BMI have been extensively
      studied in younger children the effect of sleep duration on adiposity in
      adolescents, who are undergoing rapid growth periods, is less well known. There
      is also a lack of consistent evidence on the role of sleep on other measures of
      adolescent body composition which may be more reflective of health than BMI in
      this age group. Previous research investigating whether these relationships
      differ between sexes is also inconsistent. Therefore the objective of this study
      was to investigate relationships between sleep duration and multiple body
      composition measures in older adolescents and to investigate if these
      relationships differ between boys and girls. METHODS: A web-based cross-sectional
      survey and anthropometric measurement of 685 adolescents (mean age 15.8 years)
      from 11 schools in Otago, New Zealand. Height and weight were measured by trained
      researchers and fat mass and fat-free mass were estimated using bio-impedance.
      Generalised estimating equations were used to examine associations between sleep
      duration and the following body composition measures: BMI, waist circumference
      (WC), waist-to-height ratio (WHtR), fat mass index (FMI), and fat-free mass index
      (FFMI). Analyses were adjusted for ethnicity, deprivation, the number of screens
      in the bedroom and fruit and vegetable consumption. RESULTS: When data from all
      participants were analysed together, no significant relationships were seen
      between sleep duration and any body composition measure but significant sex
      interactions were seen. An hour increase in average nightly sleep duration in
      boys only was associated with decreases of 1.2% for WC, 0.9% for WHtR, 4.5% for
      FMI and 1.4% for FFMI in multivariate models. Similar results were seen for
      weekday and weekend night sleep duration. CONCLUSIONS: Sex specific factors may
      play a role in relationships between sleep and body composition in older
      adolescents. The results in boys were most pronounced for FMI, a measure of total
      adiposity, which suggests that insufficient sleep in adolescent boys may affect
      fat mass more than lean mass and that the use of measures such as BMI may result
      in an under-estimation of relationships.

PMID- 24034353
TI  - Blockade of mitochondrial calcium uniporter prevents cardiac mitochondrial
      dysfunction caused by iron overload.
AB  - AIM: Iron overload in the heart can lead to iron-overload cardiomyopathy and
      cardiac arrhythmia. In the past decades, growing evidence has suggested that
      cardiac mitochondrial dysfunction is associated with the development of cardiac
      dysfunction and lethal arrhythmias. Despite these facts, the effect of iron
      overload on cardiac mitochondrial function is still unclear. In this study, we
      determined the effects of iron overload on the cardiac mitochondrial function and
      the routes of cardiac mitochondrial iron uptake. We tested the hypothesis that
      iron overload can lead to cardiac mitochondrial dysfunction and that
      mitochondrial calcium uniporter (MCU) plays a major role for cardiac
      mitochondrial iron uptake under iron-overload condition. Cardiac mitochondrial
      function was assessed via the determination of mitochondrial swelling,
      mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane
      potential changes. METHODS: Isolated cardiac mitochondria from male Wistar rats
      were used in this study. To determine the routes for cardiac mitochondrial iron
      uptake, isolated mitochondria were exposed to MCU blocker (Ru360), mitochondrial
      permeability transition pore (mPTP) blocker (cyclosporin A) and an iron chelator
      (deferoxamine). RESULTS: We found that (i) iron overload caused cardiac
      mitochondrial dysfunction, indicated by increased ROS production, mitochondrial
      membrane depolarization and mitochondrial swelling; and (ii) only MCU blocker
      completely protected cardiac mitochondrial dysfunction caused by iron overload.
      CONCLUSIONS: These findings strongly suggest that MCU could be the major route
      for iron uptake into cardiac mitochondria. The inhibition of MCU could be the
      novel pharmacological intervention for preventing iron-overload cardiomyopathy.

PMID- 24034354
TI  - Deformations of amygdala morphology in familial pediatric bipolar disorder.
AB  - OBJECTIVE: Smaller amygdalar volumes have been consistently observed in pediatric
      bipolar disorder subjects compared to healthy control subjects. Whether smaller
      amygdalar volume is a consequence or antecedent of the first episode of mania is
      not known. Additionally, smaller volume has not been localized to specific
      amygdala subregions. METHODS: We compared surface contour maps of the amygdala
      between 22 youths at high risk for bipolar disorder, 26 youths meeting full
      diagnostic criteria for pediatric familial bipolar disorder, and 24 healthy
      control subjects matched for age, gender, and intelligence quotient. Amygdalae
      were manually delineated on three-dimensional spoiled gradient echo images by a
      blinded rater using established tracing protocols. Statistical surface mesh
      modeling algorithms supported by permutation statistics were used to identify
      regional surface differences between the groups. RESULTS: When compared to high
      risk subjects and controls, youth with bipolar disorder showed surface
      deformations in specific amygdalar subregions, suggesting smaller volume of the
      basolateral nuclei. The high-risk subjects did not differ from controls in any
      subregion. CONCLUSIONS: These findings support previous reports of smaller
      amygdala volume in pediatric bipolar disorder and map the location of abnormality
      to specific amygdala subregions. These subregions have been associated with fear
      conditioning and emotion-enhanced memory. The absence of amygdala size
      abnormalities in youth at high risk for bipolar disorder suggests that reductions
      might occur after the onset of mania.

PMID- 24034355
TI  - An exploratory analysis of the impact of a university campus smoking ban on staff
      and student smoking habits in Japan.
AB  - BACKGROUND: Smoking bans in public places have been shown to have an impact on
      smoking habits, however the potential influence of a university smoking ban on
      faculty and staff smoking habits remains elusive. METHODS: This cross sectional
      study was implemented in Nayoro City, Japan in 2011, among the faculty and
      students of the Nayoro City University. Five years after the declaration of a
      total ban on smoking on a university campus, the smoking characteristics of all
      students, teachers and office workers, and the policy's impact on smokers were
      investigated. The survey was conducted through an anonymous, self-administered,
      multiple-choice questionnaire. Information was gathered on the characteristics
      and smoking characteristics of respondents, and the smokers attitudes toward
      smoking. RESULTS: The recovery rate was 62.1%. Among respondents, smoking
      prevalence was 17.9% in teachers and office workers, and 4.0% in students. Among
      all smokers, 46.4% did not abstain from smoking while at the university and they
      indicated their smoking areas were "on the streets next to the campus": 16 and
      "outdoors on campus": 3, respectively. As for smokers, 29.6% of them reduced the
      number of cigarettes smoked per day as a result of the smoking ban. None of the
      ex-smokers replied that their principal motivation for quitting smoking was the
      smoking ban. CONCLUSIONS: The ban on smoking served a motivator for smokers to
      reduce in smoking, but not serve as an effective motivator to quit smoking.

PMID- 24034356
TI  - Engineering stereoselectivity of ThDP-dependent enzymes.
AB  - Thiamine diphosphate-dependent enzymes are broadly distributed in all organisms,
      and they catalyse a broad range of C-C bond forming and breaking reactions.
      Enzymes belonging to the structural families of decarboxylases and transketolases
      have been particularly well investigated concerning their substrate range,
      mechanism of stereoselective carboligation and carbolyase reaction. Both
      structurally different enzyme families differ also in stereoselectivity: enzymes
      from the decarboxylase family are predominantly R-selective, whereas those from
      the transketolase family are S-selective. In recent years a key focus of our
      studies has been on stereoselective benzoin condensation-like 1,2-additions.
      Meanwhile, several S-selective variants of pyruvate decarboxylase, benzoylformate
      decarboxylase and 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate
      (SEPHCHC) synthase as well as R-selective transketolase variants were created
      that allow access to a broad range of enantiocomplementary alpha-hydroxyketones
      and alpha,alpha'-dihydroxyketones. This review covers recent studies and the
      mechanistic understanding of stereoselective C-C bond forming thiamine
      diphosphate-dependent enzymes, which has been guided by structure-function
      analyses based on mutagenesis studies and from influences of different substrates
      and organic co-solvents on stereoselectivity. 

PMID- 24034357
TI  - A whole-genome SNP array (RICE6K) for genomic breeding in rice.
AB  - The advances in genotyping technology provide an opportunity to use genomic tools
      in crop breeding. As compared to field selections performed in conventional
      breeding programmes, genomics-based genotype screen can potentially reduce number
      of breeding cycles and more precisely integrate target genes for particular
      traits into an ideal genetic background. We developed a whole-genome single
      nucleotide polymorphism (SNP) array, RICE6K, based on Infinium technology, using
      representative SNPs selected from more than four million SNPs identified from
      resequencing data of more than 500 rice landraces. RICE6K contains 5102 SNP and
      insertion-deletion (InDel) markers, about 4500 of which were of high quality in
      the tested rice lines producing highly repeatable results. Forty-five functional
      markers that are located inside 28 characterized genes of important traits can be
      detected using RICE6K. The SNP markers are evenly distributed on the 12
      chromosomes of rice with the average density of 12 SNPs per 1 Mb and can provide
      information for polymorphisms between indica and japonica subspecies as well as
      varieties within indica and japonica groups. Application tests of RICE6K showed
      that the array is suitable for rice germplasm fingerprinting, genotyping bulked
      segregating pools, seed authenticity check and genetic background selection.
      These results suggest that RICE6K provides an efficient and reliable genotyping
      tool for rice genomic breeding. 

PMID- 24034358
TI  - Center of excellence for sexual medicine.

PMID- 24034359
TI  - The cosmetic circumcision.

PMID- 24034362
TI  - Adherence to the USDA dietary recommendations for fruit and vegetable intake and
      risk of fatal stroke among ethnic groups: a prospective cohort study.
AB  - BACKGROUND: Stroke is the fourth leading cause of death in the U.S. and stroke
      mortality rates differ substantially by ethnic group. The impact of adherence to
      the USDA dietary guidelines on risk for fatal stroke among different ethnic
      groups has not previously been examined. METHODS: A prospective cohort design was
      used to examine associations between adherence with dietary recommendations for
      fruit and vegetable intake and risk for stroke mortality among 174,888 men and
      women representing five ethnic groups; African American, Native Hawaiian,
      Japanese American, Latino, and Caucasian. Dietary intake was assessed using a
      mailed quantitative food frequency questionnaire. Associations were examined
      using Cox proportional hazards models. RESULTS: There was no evidence that
      ethnicity modified associations between fruit and vegetable intake and stroke
      mortality. When data for different ethnicities were combined, a reduced risk for
      fatal stroke was observed among women who were adherent with the USDA dietary
      recommendations for vegetable intake, although this result did not reach
      statistical significance (RR = 0.84, 95% CI = 0.68-1.04). No associations were
      observed among men. CONCLUSIONS: The results of this study do not provide
      evidence that dietary intake of fruits and vegetables differentially impacts risk
      for stroke mortality among different ethnic groups.

PMID- 24034363
TI  - Biological psychiatry: raising the bar.

PMID- 24034361
TI  - Microbial alginate production, modification and its applications.
AB  - Alginate is an important polysaccharide used widely in the food, textile,
      printing and pharmaceutical industries for its viscosifying, and gelling
      properties. All commercially produced alginates are isolated from farmed brown
      seaweeds. These algal alginates suffer from heterogeneity in composition and
      material properties. Here, we will discuss alginates produced by bacteria; the
      molecular mechanisms involved in their biosynthesis; and the potential to utilize
      these bacterially produced or modified alginates for high-value applications
      where defined material properties are required. 

PMID- 24034364
TI  - Pregnancy, a risky time: keep calm, clean, and carry on!

PMID- 24034365
TI  - Enduring effects of adolescent drug exposure.

PMID- 24034366
TI  - The impact of crystalloidal and colloidal infusion preparations on coronary
      vascular integrity, interstitial oedema and cardiac performance in isolated
      hearts.
AB  - INTRODUCTION: Recent data suggested an interaction between plasma constituents
      and the endothelial glycocalyx to be relevant for vascular barrier function. This
      might be negatively influenced by infusion solutions, depending on ionic
      composition, pH and binding properties. The present study evaluated such an
      influence of current artificial preparations. METHODS: Isolated guinea pig hearts
      were prepared in a modified Langendorff mode and perfused with Krebs-Henseleit
      buffer augmented with 1g% human albumin. After equilibration the perfusion was
      switched to replacement of one half buffer by either isotonic saline (NaCl),
      ringer's acetate (Ri-Ac), 6% and 10% hydroxyethyl starch (6% and 10% HES, resp.),
      or 4% gelatine (Gel), the artificial colloids having been prepared in balanced
      solution. We analysed glycocalyx shedding, functional integrity of the vascular
      barrier and heart performance. RESULTS: While glycocalyx shedding was not
      observed, diluting albumin concentration towards 0.5g% by artificial solutions
      was associated with a marked functional breakdown of vascular barrier competence.
      This effect was biggest with isotonic saline and significantly attenuated with
      artificial colloids, the difference in the pressure dependent transvascular fluid
      filtration (basal vs. during infusion in groups NaCl, Ri-Ac, 6% HES, 10% HES and
      Gel, n = 6 each) being 0.31 +/- 0.03 vs. 1.00 +/- 0.04; 0.27 +/- 0.03 vs. 0.81 +/
      0.03; 0.29 +/- 0.03 vs. 0.68 +/- 0.02; 0.32 +/- 0.03 vs. 0.59 +/- 0.08 and 0.31
      +/- 0.04 vs. 0.61 +/- 0.03 g/5min, respectively. Heart performance was directly
      related to pH value (7.38 +/- 0.06, 7.33 +/- 0.03, 7.14 +/- 0.04, 7.08 +/- 0.04,
      7.25 +/- 0.03), the change in the rate pressure product being 21,702 +/- 1969 vs.
      21,291 +/- 2,552; 22,098 +/- 2,115 vs. 14,114 +/- 3,386; 20,897 +/- 2,083 vs.
      10,671 +/- 1,948; 21,822 +/- 2,470 vs. 10,047 +/- 2,320 and 20,955 +/- 2,296 vs.
      15,951 +/- 2,755 mmHg * bpm, respectively. CONCLUSIONS: It appears important to
      maintain the pH value within a physiological range to maintain optimal myocardial
      contractility. Using colloids prepared in calcium-containing, balanced solutions
      for volume replacement therapy may attenuate the breakdown of vascular barrier
      competence in the critically ill.

PMID- 24034367
TI  - Reframing risk part I: Legal and ethical standards for medical risk disclosure.

PMID- 24034368
TI  - Reframing risk part II: Methods for improving medical risk communication.

PMID- 24034369
TI  - Secondary syphilis and suspected child abuse.

PMID- 24034370
TI  - Outdated dermatologic drug samples and obligations to the patient.

PMID- 24034371
TI  - On the cusp of a revolution: melanoma molecular diagnostics.

PMID- 24034372
TI  - Goeckerman regimen for management of psoriasis refractory to biologic therapy:
      the University of California San Francisco experience.

PMID- 24034373
TI  - Systematic review of the efficacy and adverse events associated with infliximab
      treatment of hidradenitis suppurativa in patients with coexistent inflammatory
      diseases.

PMID- 24034374
TI  - Association of gender, tumor necrosis factor inhibitor therapy, and myocardial
      infarction risk in patients with psoriasis.

PMID- 24034375
TI  - Measuring quality of life in epidermolysis bullosa in Mexico: cross-cultural
      validation of the Hispanic version of the Quality of Life in Epidermolysis
      Bullosa questionnaire.

PMID- 24034376
TI  - Pathologic nodal evaluation is increasingly commonly performed for patients with
      Merkel cell carcinoma.

PMID- 24034377
TI  - Intravenous immunoglobulin for refractory cutaneous dermatomyositis: a
      retrospective analysis from an academic medical center.

PMID- 24034378
TI  - Isotretinoin for high-grade or refractory epidermal growth factor receptor
      inhibitor-related acneiform papulopustular eruptions.

PMID- 24034379
TI  - Kawasaki disease: part I. Diagnosis, clinical features, and pathogenesis.
AB  - Kawasaki disease, or mucocutaneous lymph node syndrome, most commonly affects
      children between 6 months and 5 years of age. Approximately 90% of patients have
      mucocutaneous manifestations. This article will focus on the epidemiology of
      Kawasaki disease in the United States as it relates to other countries, the
      diagnosis of Kawasaki disease, its clinical course, and the currently accepted
      theories of pathogenesis. A particular focus is given to the various dermatologic
      manifestations that may occur. 

PMID- 24034380
TI  - Kawasaki disease: part II. Complications and treatment.
AB  - Kawasaki disease, or mucocutaneous lymph node syndrome, is the leading cause of
      acquired heart disease in children in the United States and other developed
      countries. Coronary artery lesions are the most significant cause of morbidity
      and mortality. Treatment should ideally be provided within 10 days of symptom
      onset to reduce the risk of coronary artery complications. The standard of care
      for treatment is intravenous immunoglobulin plus aspirin, but adding
      corticosteroids may provide additional benefit for high-risk patients. Some
      patients do not respond to intravenous immunoglobulin and require additional
      therapy. Part II of this continuing medical education article will focus on the
      complications of Kawasaki disease and potential treatment options. 

PMID- 24034381
TI  - Whitish papule on the vulva.

PMID- 24034382
TI  - An unusual discoloration.

PMID- 24034383
TI  - Dermoscopy should always be performed...even in clear-cut cases!

PMID- 24034384
TI  - Small brown circles: an important diagnostic clue for pigmented squamous cell
      carcinoma.

PMID- 24034385
TI  - Hutchinson-Gilford progeria syndrome: report of 2 cases and a novel LMNA mutation
      of HGPS in China.

PMID- 24034386
TI  - Complete and rapid regression of primary cutaneous follicular lymphoma with
      repeated oral administration of acitretin for palmoplantar psoriasis.

PMID- 24034387
TI  - Neurotoxicity in the setting of pediatric atopic dermatitis treated with modified
      cyclosporine and itraconazole.

PMID- 24034388
TI  - Eruptive squamous cell carcinoma in a patient receiving abatacept for rheumatoid
      arthritis.

PMID- 24034389
TI  - Systemic involvement in TREX1-associated familial chilblain lupus.

PMID- 24034390
TI  - Clinical remission of Merkel cell carcinoma after treatment with imatinib.

PMID- 24034391
TI  - Acute generalized exanthematous pustulosis in a patient receiving high-dose
      recombinant interleukin-2.

PMID- 24034392
TI  - Successful treatment of verruciform xanthoma with imiquimod.

PMID- 24034393
TI  - Scalp melanoma in a woman with LEOPARD syndrome: possible implication of PTPN11
      signaling in melanoma pathogenesis.

PMID- 24034395
TI  - Human papillomavirus type 57 in generalized verrucosis without immunodeficiency.

PMID- 24034394
TI  - Postsurgical erosive papulonodular dermatosis.

PMID- 24034396
TI  - Infiltrating syringomatous adenoma of the nipple: a case report.

PMID- 24034397
TI  - Disseminated infection with cutaneous involvement caused by Mycobacterium
      malmoense in an immunocompromised patient.

PMID- 24034398
TI  - Is prurigo pigmentosa an inflammatory version of confluent and reticulated
      papillomatosis?

PMID- 24034399
TI  - Malignant melanoma from a nevus of Ota in a pediatric patient with fatal outcome.

PMID- 24034400
TI  - Potential exsanguination from a punch biopsy.

PMID- 24034401
TI  - Green foot syndrome: a case series of 14 patients from an armed forces hospital.

PMID- 24034402
TI  - Targetoid palmoplantar Sweet syndrome as presenting sign of severe Crohn's
      disease.

PMID- 24034403
TI  - Cutaneous lupus mucinosis successfully treated with systemic corticosteroid and
      systemic tacrolimus combination therapy.

PMID- 24034404
TI  - Dermoscopy of pseudoxanthoma elasticum-like papillary dermal elastolysis.

PMID- 24034405
TI  - Successful treatment of a chronic venous leg ulcer using a topical beta-blocker.

PMID- 24034406
TI  - Candida rib osteomyelitis: erythema and nodule in midline scar.

PMID- 24034407
TI  - Multiple minute digitate hyperkeratoses.

PMID- 24034408
TI  - Distribution of the corticobulbar tract in the internal capsule.
AB  - It is generally thought that the corticobulbar tract descends through the genu of
      the internal capsule (IC). There have been several reports that genu lesions
      cause bulbar symptoms such as facial palsies, dysarthria, and dysphagia. However,
      the precise location of the corticobulbar tract in the IC remains controversial.
      The purpose of our study is to assess whether the corticobulbar tract passes
      through the IC genu. We reviewed 26 patients with selective IC infarction and
      located the sites related to bulbar symptoms. In addition, using diffusion tensor
      imaging, we reconstructed tracts passing through the IC in ten subjects without
      cerebral infarction. Patients with genu infarction, which extended to more than
      half of the posterior limb of the IC, showed bulbar symptoms. However, patients
      with genu infarction, which was limited to the genu, did not have bulbar
      symptoms. In contrast, patients with lesions limited to the posterior limb may
      show bulbar symptoms. According to statistical maps of the region of interest,
      the lesions related to bulbar symptoms were localized to areas that were beyond
      the midpoint of the posterior limb of the IC. In diffusion tensor imaging of
      subjects without cerebral infarctions, the corticobulbar and corticospinal tracts
      did not pass through the IC genu. Our data provide evidence that the
      corticobulbar tract does not pass through the IC genu. The proposed location of
      the corticobulbar tract in the level of the IC lies beyond the midpoint of the
      posterior limb. 

PMID- 24034409
TI  - A new CSF1R mutation presenting with an extensive white matter lesion mimicking
      primary progressive multiple sclerosis.
AB  - HDLS (Hereditary Diffuse Leukodystrophy with Spheroids) is a hereditary
      leukodystrophy whose main clinical manifestations include parkinsonism,
      spasticity, and ataxia. Genetic defects in the colony-stimulating factor 1
      receptor (CSF1R) gene have been reported in many HDLS cases. The present report
      describes a new missense mutation Arg777Gln involving exon 18 of the CSF1R gene
      in a sporadic patient presenting with tumor-like lesions mimicking primary
      progressive multiple sclerosis. The patient was initially diagnosed with a
      progressive variant of multiple sclerosis and received inadequate treatments.
      Although most HDLS cases have a positive family history, this disease should also
      be suspected in sporadic patients showing unusual white matter lesions at MRI. 

PMID- 24034410
TI  - How long does it take to diagnose cervical dystonia?
AB  - BACKGROUND: Dystonia is a neurological disorder characterized by involuntary
      twisting movements and postures. The neck is among the most commonly affected
      regions, and diagnosis can be made readily through a simple clinical evaluation.
      The goal of this study was to explore how long it took patients to receive a
      diagnosis of cervical dystonia after symptom onset. METHODS: A structured
      questionnaire was administered at outpatient clinics of a tertiary care academic
      medical center to 146 consecutively evaluated patients. The questionnaire
      addressed the length of time from symptom onset to diagnosis, the numbers and
      types of providers seen before reaching a diagnosis, and treatments attempted
      prior to receiving botulinum toxin. RESULTS: A total of 108 patients saw a mean
      of 3.5 providers over a mean period of 44 months from symptom onset to diagnosis.
      For patients with symptom onset in the last decade only, patients saw a mean of
      3.0 providers over a mean of 14 months. CONCLUSIONS: Although cervical dystonia
      is the most common form of dystonia with clinical features readily identifiable
      by a simple history and examination, patients typically see multiple providers
      over more than a year before reaching a diagnosis and receiving optimal therapy.
      Improved awareness of the clinical features will enable patients to obtain
      appropriate therapy more rapidly.

PMID- 24034411
TI  - Association between physical activity and serum C-peptide levels among the
      elderly.
AB  - AIM: Serum C-peptide is an active peptide that has important physiological
      functions and characteristics in the elderly. The present study aimed to
      investigate the association between physical activity and serum C-peptide level
      independent of insulin level among the elderly. METHODS: The study included 1700
      elderly participants aged >= 65 years. Stratified analysis of covariance was used
      to compare serum C-peptide levels in participants with different physical
      activity levels. Two separate multiple linear regression models were created to
      estimate the association between physical activity and serum C-peptide level.
      RESULTS: The results of analysis of covariance stratified by sex, body mass index
      and serum insulin level showed that those who engaged in vigorous physical
      activity had lower serum C-peptide levels than those who engaged in light or no
      physical activity. Separate multiple linear regression analysis showed that in
      those with low serum C-peptide levels (<= 0.621 nmol/L), physical activity was
      significantly positively associated with the serum C-peptide level. In contrast,
      physical activity was negatively associated with the serum C-peptide level among
      those with serum C-peptide level >0.621 nmol/L. CONCLUSIONS: The serum C-peptide
      level showed a significant two-way association with physical activity. The
      present findings suggest that physical activity modification is important for
      improving serum C-peptide levels among the elderly.

PMID- 24034412
TI  - Different B-type methionine sulfoxide reductases in Chlamydomonas may protect the
      alga against high-light, sulfur-depletion, or oxidative stress.
AB  - The genome of unicellular green alga Chlamydomonas reinhardtii contains four
      genes encoding B-type methionine sulfoxide reductases, MSRB1.1, MSRB1.2, MSRB2.1,
      and MSRB2.2, with functions largely unknown. To understand the cell defense
      system mediated by the methionine sulfoxide reductases in Chlamydomonas, we
      analyzed expression and physiological roles of the MSRBs under different abiotic
      stress conditions using immunoblotting and quantitative polymerase chain reaction
      (PCR) analyses. We showed that the MSRB2.2 protein was accumulated in cells
      treated with high light (1,300 uE/m2 per s), whereas MSRB1.1 was accumulated in
      the cells under 1 mmol/L H2O2 treatment or sulfur depletion. We observed that the
      cells with the MSRB2.2 knockdown and overexpression displayed increased and
      decreased sensitivity to high light, respectively, based on in situ chlorophyll a
      fluorescence measures. We also observed that the cells with the MSRB1.1 knockdown
      and overexpression displayed decreased and increased tolerance to sulfur
      depletion and oxidative stresses, respectively, based on growth and H2-producing
      performance. The physiological implications revealed from the experimental data
      highlight the importance of MSRB2.2 and MSRB1.1 in protecting Chlamydomonas cells
      against adverse conditions such as high-light, sulfur-depletion, and oxidative
      stresses.

PMID- 24034413
TI  - Bioaccumulation and ecotoxicity of carbon nanotubes.
AB  - Carbon nanotubes (CNT) have numerous industrial applications and may be released
      to the environment. In the aquatic environment, pristine or functionalized CNT
      have different dispersion behavior, potentially leading to different risks of
      exposure along the water column. Data included in this review indicate that CNT
      do not cross biological barriers readily. When internalized, only a minimal
      fraction of CNT translocate into organism body compartments. The reported CNT
      toxicity depends on exposure conditions, model organism, CNT-type, dispersion
      state and concentration. In the ecotoxicological tests, the aquatic organisms
      were generally found to be more sensitive than terrestrial organisms.
      Invertebrates were more sensitive than vertebrates. Single-walled CNT were found
      to be more toxic than double-/multi-walled CNT. Generally, the effect
      concentrations documented in literature were above current modeled average
      environmental concentrations. Measurement data are needed for estimation of
      environmental no-effect concentrations. Future studies with benchmark materials
      are needed to generate comparable results. Studies have to include better
      characterization of the starting materials, of the dispersions and of the
      biological fate, to obtain better knowledge of the exposure/effect relationships.

PMID- 24034415
TI  - How good is controlled attenuation parameter and fatty liver index for assessing
      liver steatosis in general population: correlation with ultrasound.
AB  - BACKGROUND & AIMS: Liver steatosis measurement by controlled attenuation
      parameter (CAP) is a non-invasive method for diagnosing steatosis, based on
      transient elastography. Its usefulness as screening procedure for hepatic
      steatosis in general population has not been previously evaluated. The aim of
      this study was to evaluate the diagnostic accuracy of CAP and fatty liver index
      (FLI) for detection and quantification of steatosis in general population.
      METHODS: Recruitment was done from a prospective epidemiological study of the
      general adult population. Steatosis was evaluated using CAP, FLI and ultrasound
      (US). Steatosis scored according to Hamaguchi's US scoring, from 0 (S0) to 6 (S6)
      points. Hepatic steatosis defined by score >=2 (S>=2) and moderate/severe
      steatosis by score >=4 (S>=4). Performance of CAP and FLI for diagnosing
      steatosis compared with US was assessed using areas under receiver operating
      characteristic curves (AUROC). RESULTS: From 219 consecutive individuals studied,
      13 (5.9%) excluded because of failure/unreliable liver stiffness measurements.
      Steatosis prevalence: S>=2 38.4% and S>=4 12.1%. CAP significantly correlated
      with steatosis (rho = 0.73, P < 0.0001), steatosis score (rho = 0.76; P <
      0.0001), FLI (rho = 0.69), waist circumference (rho = 0.62), body mass index (rho
      = 0.55), triglyceride (rho = 0.49), HOMA-IR (rho = 0.26), alcohol consumption
      (rho = 0.24) and cholesterol (rho = 0.19), not with liver stiffness measurements.
      Using CAP and FLI, AUROC's were 0.94 (95% CI 0.91-0.97, P < 0.001) and 0.91 for
      S>=2; 0.95 (95% CI 0.90-0.99, P < 0.001) and 0.93 for S>=4 respectively. Optimal
      cut-off value of CAP and FLI were 243 dB/m and 48 for S>=2; 303.5 dB/m and 62 for
      S>=4 respectively. CONCLUSION: Controlled attenuation parameter and FLI seem
      promising tools for screening and steatosis quantification in the general
      population. Larger studies are needed for validation.

PMID- 24034416
TI  - Identifying indicators of colorectal cancer care coordination: a Delphi study.
AB  - AIM: Care coordination is an important aspect of the quality of cancer care but
      is difficult to evaluate due to the lack of valid and reliable measures. This
      study was conducted to identify a set of objective measures of colorectal cancer
      care coordination that could be included in a medical record audit tool. METHOD:
      A two-stage Delphi study was conducted to gain consensus among a national panel
      of experts about the validity of 41 potential indicators of colorectal cancer
      care coordination that had been identified during a literature review. The expert
      panel comprised 20 members from the National Health and Medical Research
      Colorectal Cancer Guidelines Working Party plus representatives from cancer
      nursing/coordination, general practice and cancer consumers. RESULTS: Consensus
      was reached on the validity of 15 of 41 potential indicators, including those
      that focused on practical aspects of communication (legibility, clarity, content
      and timeliness of hospital discharge letters, documentation of outcomes of
      multidisciplinary team meetings) and appropriateness (documentation of
      preoperative consultation with a stoma therapist, discussions and referrals for
      adjuvant therapy for appropriate patients, and treatment by an experienced
      colorectal surgeon). There was lack of consensus on the validity of indicators
      relating to access to and efficiency of services. CONCLUSION: The study has
      identified a core set of measures considered to be valid indicators of colorectal
      cancer care coordination. A medical record audit based on these measures could be
      used to monitor adequacy of cancer care coordination and will complement
      subjective measures based on self-reported experiences of patients and carers.

PMID- 24034414
TI  - Prenatal glucocorticoids and maternal smoking during pregnancy independently
      program adult nicotine dependence in daughters: a 40-year prospective study.
AB  - BACKGROUND: Maternal smoking during pregnancy (MSDP) is an independent risk
      factor for offspring nicotine dependence (ND), but mechanisms remain unknown. We
      investigated prenatal glucocorticoid (cortisol) and androgen (testosterone)
      associations with offspring ND over 40 years and the possibility that prenatal
      glucocorticoids and androgens would mediate links between MSDP and offspring ND.
      METHODS: Participants were 1086 mother-adult offspring pairs (59% female) from
      the New England Family Study, a 40-year longitudinal follow-up of the
      Collaborative Perinatal Project. MSDP was assessed prospectively at each prenatal
      visit. Maternal cortisol, testosterone, and cotinine (nicotine metabolite) were
      assayed from third trimester maternal sera. Offspring lifetime ND was assessed
      via structured interview. RESULTS: Significant bivariate associations emerged
      for: 1) MSDP/cotinine and lifetime ND; and 2) maternal cortisol and lifetime ND,
      for daughters only. In multivariate models, maternal cortisol and MSDP/cotinine
      remained significantly and independently associated with increased odds of
      lifetime ND of daughters. However, cortisol did not mediate the MSDP-lifetime ND
      relation. No associations emerged between maternal testosterone and offspring ND.
      CONCLUSIONS: Results provide the first evidence in support of prenatal
      glucocorticoid programming of adult ND over 40 years in daughters only. Our study
      highlights two independent prenatal pathways leading to increased risk for ND in
      daughters: elevated prenatal glucocorticoids and MSDP/nicotine exposure. Daughter
      specific effects of glucocorticoid and MSDP programming over 40 years highlight
      the breadth and persistence of sexually dimorphic programming effects in humans.
      Results do not support androgen programming of offspring ND.

PMID- 24034417
TI  - Health inequity in the Northern Territory, Australia.
AB  - INTRODUCTION: Understanding health inequity is necessary for addressing the
      disparities in health outcomes in many populations, including the health gap
      between Indigenous and non-Indigenous Australians. This report investigates the
      links between Indigenous health outcomes and socioeconomic disadvantage in the
      Northern Territory of Australia (NT). METHODS: Data sources include deaths,
      public hospital admissions between 2005 and 2007, and Socio-Economic Indexes for
      Areas from the 2006 Census. Age-sex standardisation, standardised rate ratio,
      concentration index and Poisson regression model are used for statistical
      analysis. RESULTS: There was a strong inverse association between socioeconomic
      status (SES) and both mortality and morbidity rates. Mortality and morbidity
      rates in the low SES group were approximately twice those in the medium SES
      group, which were, in turn, 50% higher than those in the high SES group. The
      gradient was present for most disease categories for both deaths and hospital
      admissions. Residents in remote and very remote areas experienced higher
      mortality and hospital morbidity than non-remote areas. Approximately 25-30% of
      the NT Indigenous health disparity may be explained by socioeconomic
      disadvantage. CONCLUSIONS: Socioeconomic disadvantage is a shared common
      denominator for the main causes of deaths and principal diagnoses of
      hospitalisations for the NT population. Closing the gap in health outcomes
      between Indigenous and non-Indigenous populations will require improving the
      socioeconomic conditions of Indigenous Australians.

PMID- 24034418
TI  - A role for the DtxR family of metalloregulators in gram-positive pathogenesis.
AB  - Given the central role of transition metal ions in a variety of biochemical
      processes, the colonization, survival, and proliferation of a bacterium within a
      host hinges upon its ability to overcome the metal ion deprivation that
      characterizes nutritional immunity. Metalloregulatory, or 'metal-sensing'
      proteins have evolved in bacteria to mediate metal ion homeostasis by activating
      or repressing the expression of genes encoding metal ion transport systems upon
      binding their cognate metal ion. Yet increasing evidence in the literature
      supports an additional role for these metalloregulatory proteins in pathogenesis.
      Herein, we survey studies on the DtxR family of metalloregulators, namely DtxR
      (Cornyebacterium diphtheriae), SloR (Streptococcus mutans), MtsR (Streptococcus
      pyogenes), and MntR (Staphylococcus aureus) to describe how metalloregulation
      enables adaptive virulence gene expression within the mammalian host. This
      research has important implications for drug design, as the generation of hyper
      repressive metalloregulatory proteins may represent a mechanism by which to
      attenuate bacterial pathogenicity. The fact that metalloregulators are unique to
      prokaryotes makes these proteins especially attractive therapeutic targets. 

PMID- 24034420
TI  - Increased N-terminal cleavage of alpha-2-antiplasmin in patients with liver
      cirrhosis.
AB  - BACKGROUND: The activity of alpha-2-antiplasmin (alpha2AP), the main fibrinolytic
      inhibitor, is modified by N- and C-terminal proteolytic cleavages. C-terminal
      cleavage converts plasminogen-binding alpha2AP (PB-alpha2AP) into a non
      plasminogen-binding derivative. N-terminal cleavage by antiplasmin-cleaving
      enzyme (APCE), a soluble, circulating derivative of fibroblast activation protein
      (FAP), turns native Met-alpha2AP into Asn-alpha2AP, which is more quickly
      crosslinked into fibrin. OBJECTIVES: We developed two novel enzyme-linked
      immunosorbent assays (ELISAs) to determine the N-terminal variation of alpha2AP
      to test the hypothesis that liver cirrhosis, characterized by increased
      expression of FAP/APCE, results in increased N-terminal cleavage of alpha2AP.
      PATIENTS/METHODS: alpha2AP and FAP/APCE antigen levels were measured in the
      plasma samples of 75 patients with cirrhosis with different severities and 30
      healthy control individuals. The percentage of N-terminal cleavage of alpha2AP
      was calculated. RESULTS: Compared with levels (median [interquartile range]) in
      control individuals, total PB-alpha2AP levels and Met-PB-alpha2AP levels were
      reduced in cirrhosis patients (27.3 [21.4-41.3] MUg mL(-1) vs. 56.2 [49.6-62.8]
      MUg mL(-1) , P < 0.001, and 2.7 [1.7-5.5] MUg mL(-1) vs. 12.1 [11.0-15.3] MUg mL(
      1) , P < 0.001, respectively). Interestingly, the percentage of N-terminal
      cleavage was increased in the patients (87.8 [85.0-91.6]% vs. 77.2 [72.2-79.8]%
      in controls, P < 0.001), as well as the plasma FAP/APCE levels (166 [60-550] ng
      mL(-1) in patients vs. 107 [67-157] ng mL(-1) in controls, P < 0.001).
      Additionally, all variables significantly correlated with the severity of
      disease. CONCLUSIONS: Using our novel ELISAs we found increased N-terminal
      cleavage of alpha2AP in liver cirrhosis patients, which correlated with the
      severity of disease and is likely to have reflected the increased FAP/APCE levels
      in these patients.

PMID- 24034419
TI  - Disturbances in reality testing as markers of risk in offspring of parents with
      bipolar disorder: a systematic review from a developmental psychopathology
      perspective.
AB  - OBJECTIVES: This comprehensive review examined the prevalence and progression of
      disturbances in reality testing (DRT), defined as psychotic symptoms, cognitive
      disruptions, and thought problems, in offspring of parents with bipolar disorder
      (O-BD). Our approach was grounded in a developmental psychopathology perspective
      and considered a broader phenotype of risk within the bipolar-schizophrenia
      spectrum as measured by categorical and dimensional assessments of DRT in high
      risk youth. METHODS: Relevant studies were identified from numerous sources
      (e.g., PubMed, reference sections, and colleagues). Inclusion criteria were: (i)
      family risk studies published between 1975 and 2012 in which O-BD were contrasted
      with a comparison group (e.g., offspring of parents who had other psychiatric
      disorders or were healthy) on DRT outcomes and (ii) results reported for
      categorical or dimensional assessments of DRT (e.g., schizophrenia, psychotic
      symptoms, cluster A personality traits, or thought problems), yielding a total of
      23 studies. RESULTS: Three key findings emerged: (i) categorical approaches of
      DRT in O-BD produced low incidence base rates and almost no evidence of
      significant differences in DRT between O-BD and comparison groups, whereas (ii)
      many studies using dimensional assessments of DRT yielded significant group
      differences in DRT. Furthermore, (iii) preliminary evidence from dimensional
      measures suggested that the developmental progression of DRT in O-BD might
      represent a prodrome of severe psychological impairment. CONCLUSIONS: Preliminary
      but promising evidence suggests that DRT is a probable marker of risk for future
      impairment in O-BD. Methodological strengths and weaknesses, the psychometric
      properties of primary DRT constructs, and future directions for developmental and
      longitudinal research with O-BD are discussed.

PMID- 24034421
TI  - Fractal-like kinetics of intracellular enzymatic reactions: a chemical framework
      of endotoxin tolerance and a possible non-specific contribution of macromolecular
      crowding to cross-tolerance.
AB  - BACKGROUND: The response to endotoxin (LPS), and subsequent signal transduction
      lead to the production of cytokines such as tumor necrosis factor-alpha (TNF
      alpha) by innate immune cells. Cells or organisms pretreated with endotoxin enter
      into a transient state of hyporesponsiveness, referred to as endotoxin tolerance
      (ET) which represents a particular case of negative preconditioning. Despite
      recent progress in understanding the molecular basis of ET, there is no consensus
      yet on the primary mechanism responsible for ET and for the more complex cases of
      cross tolerance. In this study, we examined the consequences of the
      macromolecular crowding (MMC) and of fractal-like kinetics (FLK) of intracellular
      enzymatic reactions on the LPS signaling machinery. We hypothesized that this
      particular type of enzyme kinetics may explain the development of ET phenomenon.
      METHOD: Our aim in the present study was to characterize the chemical kinetics
      framework in ET and determine whether fractal-like kinetics explains, at least in
      part, ET. We developed an ordinary differential equations (ODE) mathematical
      model that took into account the links between the MMC and the LPS signaling
      machinery leading to ET. We proposed that the intracellular fractal environment
      (MMC) contributes to ET and developed two mathematical models of enzyme kinetics:
      one based on Kopelman's fractal-like kinetics framework and the other based on
      Savageau's power law model. RESULTS: Kopelman's model provides a good image of
      the potential influence of a fractal intracellular environment (MMC) on ET. The
      Savageau power law model also partially explains ET. The computer simulations
      supported the hypothesis that MMC and FLK may play a role in ET. CONCLUSION: The
      model highlights the links between the organization of the intracellular
      environment, MMC and the LPS signaling machinery leading to ET. Our FLK-based
      model does not minimize the role of the numerous negative regulatory factors. It
      simply draws attention to the fact that macromolecular crowding can contribute
      significantly to the induction of ET by imposing geometric constrains and a
      particular chemical kinetic for the intracellular reactions.

PMID- 24034422
TI  - Serum total bilirubin levels and prevalence of diabetic retinopathy in a Chinese
      population.
AB  - BACKGROUND: Patients with type 2 diabetes (T2D) are at a high risk of developing
      microvascular complications, such as diabetic retinopathy (DR). Previous studies
      have shown that low serum bilirubin concentrations in T2D patients may increase
      the risk of diabetic complications. Thus, the aim of the present was to
      investigate the association between the prevalence of DR and serum concentrations
      of total bilirubin in a Chinese population. METHODS: The present study was a
      population-based cross-sectional study on 1761 T2D patients aged >=40 years from
      the Jiading district of Shanghai, China. Fundus photographs were taken to confirm
      the presence and severity of DR. Subjects were assigned to quartiles based on
      serum total bilirubin concentrations (Quartile (Q) 1 <0.60 mg/dL; Q2 0.60-0.76
      mg/dL; Q3 0.77-0.99 mg/dL; Q4 >0.99 mg/dL). Logistic regression models were used
      to explore the association between bilirubin concentrations and the prevalence of
      DR. RESULTS: The prevalence of DR in the entire study population was 9.6%. The
      prevalence of DR was significantly lower in Q4 compared with the other three
      quartiles (Ptrend  = 0.004). After adjustment for multiple confounding factors,
      T2D patients in Q4 (i.e. serum bilirubin >0.99 mg/dL) were less likely (odds
      ratio 0.55; 95% confidence interval 0.33-0.91) to suffer from DR than patients in
      Q1 (i.e. serum bilirubin <0.60 mg/dL). CONCLUSION: Serum bilirubin concentrations
      were inversely associated with DR in an elderly Chinese population, independent
      of traditional risk factors for microvascular complications.

PMID- 24034423
TI  - Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms.
AB  - The incidence of thyroid cancer has been rising over the past few decades along
      with a parallel increase in obesity. Observational studies have provided evidence
      for a potential association between the two. By contrast, clinical data for a
      link between type 2 diabetes mellitus, a condition strongly associated with
      obesity, and thyroid cancer are limited and largely not supportive of such an
      association. Obesity leads to hypoadiponectinemia, a pro-inflammatory state, and
      insulin resistance, which, in turn, leads to high circulating insulin and insulin
      like growth factor-1 levels, thereby possibly increasing the risk for thyroid
      cancer. Thus, insulin resistance possibly plays a pivotal role in underlying the
      observed association between obesity and thyroid cancer, potentially leading to
      the development and/or progression of thyroid cancer, through its
      interconnections with other factors including insulin-like growth factor-1,
      adipocytokines/cytokines and thyroid-stimulating hormone. In this review,
      epidemiological and clinical evidence and potential mechanisms underlying the
      proposed association between obesity and thyroid cancer risk are reviewed. If the
      association between obesity and thyroid cancer demonstrated in observational
      studies proves to be causal, targeting obesity (and/or downstream mediators of
      risk) could be of importance in the prevention and management of thyroid cancer. 

PMID- 24034424
TI  - Women with provoked vestibulodynia experience clinically significant reductions
      in pain regardless of treatment: results from a 2-year follow-up study.
AB  - INTRODUCTION: Provoked vestibulodynia (PVD) is a prevalent genital pain syndrome
      that has been assumed to be chronic, with little spontaneous remission. Despite
      this assumption, there is a dearth of empirical evidence regarding the
      progression of PVD in a natural setting. Although many treatments are available,
      there is no single treatment that has demonstrated efficacy above others. AIMS:
      The aims of this secondary analysis of a prospective study were to (i) assess
      changes over a 2-year period in pain, depressive symptoms, and sexual outcomes in
      women with PVD; and (ii) examine changes based on treatment(s) type. METHODS:
      Participants completed questionnaire packages at Time 1 and a follow-up package 2
      years later. MAIN OUTCOME MEASURES: Visual analog scale of genital pain, Global
      Measure of Sexual Satisfaction, Female Sexual Function Index, Beck Depression
      Inventory, Dyadic Adjustment Scale, and sexual intercourse attempts over the past
      month. RESULTS: Two hundred thirty-nine women with PVD completed both time one
      and two questionnaires. For the sample as a whole, there was significant
      improvement over 2 years on pain ratings, sexual satisfaction, sexual function,
      and depressive symptoms. The most commonly received treatments were physical
      therapy, sex/psychotherapy, and medical treatment, although 41.0% did not undergo
      any treatment. Women receiving no treatment also improved significantly on pain
      ratings. No single treatment type predicted better outcome for any variable
      except depressive symptoms, in which women who underwent surgery were more likely
      to improve. DISCUSSION: These results suggest that PVD may significantly reduce
      in severity over time. Participants demonstrated clinically significant pain
      improvement, even when they did not receive treatment. Furthermore, the only
      single treatment type predicting better outcomes was surgery, and only for
      depressive symptoms, accounting for only 2.3% of the variance. These data do not
      demonstrate the superiority of any one treatment and underscore the need to have
      control groups in PVD treatment trials, otherwise improvements may simply be the
      result of natural progression.

PMID- 24034425
TI  - Women with disability: the experience of maternity care during pregnancy, labour
      and birth and the postnatal period.
AB  - BACKGROUND: It has been estimated that 9.4% of women giving birth in the United
      Kingdom have one or more limiting longstanding illness which may cause
      disability, affecting pregnancy, birth and early parenting. No large scale
      studies on a nationally representative population have been carried out on the
      maternity experiences of disabled women to our knowledge. METHOD: Secondary
      analysis of data from a survey of women in 2010 by English National Health
      Service Trusts on behalf of the Care Quality Commission was undertaken. 144
      trusts in England took part in the postal survey.Women self-identified with
      disability and were excluded if less than 16 years of age or if their baby had
      died. The 12 page structured questionnaire with sections on antenatal, labour and
      birth and postnatal care covered access, information, communication and choice.
      Descriptive and adjusted analyses compared disabled and non-disabled groups.
      Comparisons were made separately for five disability subgroups: physical
      disability, sensory impairment, mental health conditions, learning disability and
      women with more than one type of disability. RESULTS: Disabled women comprised
      6.14% (1,482) of the total sample (24,155) and appeared to use maternity services
      more than non-disabled women. Most were positive about their care and reported
      sufficient access and involvement, but were less likely to breastfeed. The
      experience of women with different types of disability varied: physically
      disabled women used antenatal and postnatal services more, but had less choice
      about labour and birth; the experience of those with a sensory impairment
      differed little from the non-disabled women, but they were more likely to have
      met staff before labour; women with mental health disabilities also used services
      more, but were more critical of communication and support; women with a learning
      disability and those with multiple disabilities were least likely to report a
      positive experience of maternity care. CONCLUSION: This national study describes
      disabled women's experiences of pregnancy, child birth and postnatal care in
      comparison with non-disabled women. While in many areas there were no
      differences, there was evidence of specific groups appropriately receiving more
      care. Areas for improvement included infant feeding and better communication in
      the context of individualised care.

PMID- 24034426
TI  - Reducing assembly complexity of microbial  genomes with single-molecule
      sequencing.
AB  - BACKGROUND: The short reads output by first- and second-generation DNA sequencing
      instruments cannot completely reconstruct microbial chromosomes. Therefore, most
      genomes have been left unfinished due to the significant resources required to
      manually close gaps in draft assemblies. Third-generation, single-molecule
      sequencing addresses this problem by greatly increasing sequencing read length,
      which simplifies the assembly problem. RESULTS: To measure the benefit of single
      molecule sequencing on microbial genome assembly, we sequenced and assembled the
      genomes of six bacteria and analyzed the repeat complexity of 2,267 complete
      bacteria and archaea. Our results indicate that the majority of known bacterial
      and archaeal genomes can be assembled without gaps, at finished-grade quality,
      using a single PacBio RS sequencing library. These single-library assemblies are
      also more accurate than typical short-read assemblies and hybrid assemblies of
      short and long reads. CONCLUSIONS: Automated assembly of long, single-molecule
      sequencing data reduces the cost of microbial finishing to $1,000 for most
      genomes, and future advances in this technology are expected to drive the cost
      lower. This is expected to increase the number of completed genomes, improve the
      quality of microbial genome databases, and enable high-fidelity, population-scale
      studies of pan-genomes and chromosomal organization.

PMID- 24034427
TI  - Detoxification of sulfur mustard by enzyme-catalyzed oxidation using
      chloroperoxidase.
AB  - One of the most interesting methods for the detoxification of sulfur mustard is
      enzyme-catalyzed oxidation. This study examined the oxidative destruction of a
      sulfur mustard by the enzyme chloroperoxidase (EC 1.11.1.10). Chloroperoxidase
      (CPO) belongs to a group of enzymes that catalyze the oxidation of various
      organic compounds by peroxide in the presence of a halide ion. The enzymatic
      oxidation reaction is affected by several factors: pH, presence or absence of
      chloride ion, temperature, the concentrations of hydrogen peroxide and enzyme and
      aqueous solubility of the substrate. The optimum reaction conditions were
      determined by analyzing the effects of all factors, and the following conditions
      were selected: solvent, Britton-Robinson buffer (pH=3) with tert-butanol (70:30
      v/v); CPO concentration, 16U/mL; hydrogen peroxide concentration, 40mmol/L;
      sodium chloride concentration, 20mmol/L. Under these reaction conditions, the
      rate constant for the reaction is 0.006s(-1). The Michaelis constant, a measure
      of the affinity of an enzyme for a particular substrate, is 1.87*10(-3)M for this
      system. The Michaelis constant for enzymes with a high affinity for their
      substrate is in the range of 10(-5) to 10(-4)M, so this value indicates that CPO
      does not have a very high affinity for sulfur mustard. 

PMID- 24034428
TI  - Effect of cell senescence on the impedance measurement of adipose tissue-derived
      stem cells.
AB  - Label-free and real-time monitoring of stem cells based on electrical impedance
      measurement is increasingly utilized for the quality control of the isolated stem
      cells to be used in stem cell-based tissue therapy or regenerative medicine. In
      spite of that the proliferative capacity and multipotency of stem cells are
      dependent on the type and age of the source tissue, however, the effect of the
      cell senescence on the impedance measurement of stem cells has not yet been
      studied. We investigated whether the senescence of adipose tissue-derived stem
      cells (ADSCs) can be detected by electrical impedance spectroscopy. For this,
      ADSCs at passage 9 and 31 were prepared and those genetic characteristics and
      growth kinetics were evaluated by quantitative polymerase chain reaction and cell
      counting. While the identified ADSCs were grown on the indium tin oxide
      electrodes, the impedance spectra were measured and interpreted by fitting
      analysis with an equivalent circuit model. ADSCs at passage 9 adhered on the
      electrode were small and spindle-shaped whereas the cells at passage 31 were
      flattened and larger than younger cells. At the beginning of culture time when
      the cell adhesion occurred, the resistance at 4.6kHz of passage 31 cells was
      higher than passage 9 due to the larger size of older cells. Afterwards, the
      value of passage 9 cells increased higher than passage 31, since younger cells
      proliferated more than old cells. Therefore, the impedance measurement could
      characterize the proliferative capacity of ADSCs during expanded culture. 

PMID- 24034429
TI  - Improvement of thermostable aldehyde dehydrogenase by directed evolution for
      application in Synthetic Cascade Biomanufacturing.
AB  - The aldehyde dehydrogenase from Thermoplasma acidophilum, which was previously
      implemented as a key enzyme in a synthetic cell-free reaction cascade for the
      production of alcohols, was optimized by directed evolution. Improvements have
      been made to enhance reaction velocity and solubility. Using a random approach
      followed by site-directed and saturation mutagenesis, three beneficial amino acid
      mutations were found after screening of ca. 20,000 variants. Mutation Y399C
      enhanced the protein solubility after recombinant expression in Escherichia coli
      6-fold. Two further mutations, F34M and S405N, enhanced enzyme activity with the
      cofactor NAD(+) by a factor of eight. Impacts on enzyme stability and substrate
      specificity were negligible. Modeling of the enzyme structure did not reveal any
      direct interactions between the amino acid substitutions and residues of the
      active site or the enzyme's substrates. Thus, a directed evolution approach
      allowed for the generation of improved enzyme variants which were unlikely to be
      found by rational or semi-rational strategies. 

PMID- 24034430
TI  - Cellulase-lignin interactions-the role of carbohydrate-binding module and pH in
      non-productive binding.
AB  - Non-productive cellulase adsorption onto lignin is a major inhibitory mechanism
      preventing enzymatic hydrolysis of lignocellulosic feedstocks. Therefore,
      understanding of enzyme-lignin interactions is essential for the development of
      enzyme mixtures and processes for lignocellulose hydrolysis. We have studied
      cellulase-lignin interactions using model enzymes, Melanocarpus albomyces Cel45A
      endoglucanase (MaCel45A) and its fusions with native and mutated carbohydrate
      binding modules (CBMs) from Trichoderma reesei Cel7A. Binding of MaCel45A to
      lignin was dependent on pH in the presence and absence of the CBM; at high pH,
      less enzyme bound to isolated lignins. Potentiometric titration of the lignin
      preparations showed that negatively charged groups were present in the lignin
      samples and that negative charge in the samples was increased with increasing pH.
      The results suggest that electrostatic interactions contributed to non-productive
      enzyme adsorption: Reduced enzyme binding at high pH was presumably due to
      repulsive electrostatic interactions between the enzymes and lignin. The CBM
      increased binding of MaCel45A to the isolated lignins only at high pH.
      Hydrophobic interactions are probably involved in CBM binding to lignin, because
      the same aromatic amino acids that are essential in CBM-cellulose interaction
      were also shown to contribute to lignin-binding. 

PMID- 24034431
TI  - Enhanced production of bioethanol from waste of beer fermentation broth at high
      temperature through consecutive batch strategy by simultaneous saccharification
      and fermentation.
AB  - Malt hydrolyzing enzymes and yeast glycolytic and fermentation enzymes in the
      waste from beer fermentation broth (WBFB) were identified by sodium dodecyl
      sulfate polyacrylamide gel electrophoresis (SDS-PAGE). A new 'one-pot consecutive
      batch strategy' was developed for efficient bio-ethanol production by
      simultaneous saccharification and fermentation (SSF) using WBFB without
      additional enzymes, microbial cells, or carbohydrates. Bio-ethanol production was
      conducted in batches using WBFB supernatant in the first phase at 25-67 degrees C
      and 50rpm, followed by the addition of 3% WBFB solid residue to the existing
      culture broth in the second phase at 67 degrees C. The ethanol production
      increased from 50 to 102.5g/L when bare supernatant was used in the first phase,
      and then to 219g ethanol/L in the second phase. The amount of ethanol obtained
      using this strategy was almost equal to that obtained using the original WBFB
      containing 25% solid residue at 33 degrees C, and more than double that obtained
      when bare supernatant was used. Microscopic and gel electrophoresis studies
      revealed yeast cell wall degradation and secretion of cellular material into the
      surrounding medium. Scanning electron microscopy (SEM) and Fourier transform
      infrared spectroscopy (FTIR) supported the existence of enzymes in WBFB involved
      in bioethanol production at elevated temperatures. The results of this study will
      provide insight for the development of new strategies for biofuel production. 

PMID- 24034432
TI  - High production of cold-tolerant chitinases on shrimp wastes in bench-top
      bioreactor by the Antarctic fungus Lecanicillium muscarium CCFEE 5003: bioprocess
      optimization and characterization of two main enzymes.
AB  - The Antarctic fungus Lecanicillium muscarium CCFEE-5003 was preliminary
      cultivated in shaken flasks to check its chitinase production on rough shrimp and
      crab wastes. Production on shrimp shells was much higher than that on crab shells
      (104.6+/-9.3 and 48.6+/-3.1U/L, respectively). For possible industrial
      applications, bioprocess optimization was studied on shrimp shells in bioreactor
      using RSM to state best conditions of pH and substrate concentration.
      Optimization improved the production by 137% (243.6+/-17.3). Two chitinolytic
      enzymes (CHI1 and CHI2) were purified and characterized. CHI1 (MW ca. 61kDa)
      showed optima at pH 5.5 and 45 degrees C while CHI2 (MW ca. 25kDa) optima were at
      pH 4.5 and 40 degrees C. Both enzymes maintained high activity levels at 5
      degrees C and were inhibited by Fe(++), Hg(++) and Cu(++). CHI2 was strongly
      allosamidin-sensitive. Both proteins were N-acetyl-hexosaminidases (E.C.
      3.2.1.52) but showed different roles in chitin hydrolysis: CHI1 could be defined
      as "chitobiase" while CHI2 revealed a main "eso-chitinase" activity. 

PMID- 24034433
TI  - Utilization of proteinaceous materials for power generation in a mediatorless
      microbial fuel cell by a new electrogenic bacteria Lysinibacillus sphaericus VA5.
AB  - In this study, a bacterial strain, Lysinibacillus sphaericus which is relatively
      new in the vast list of biocatalysts known to produce electricity has been tested
      for its potential in power production. It is cited from the literature that the
      organism is deficient in some sugar or polysaccharide processing enzymes and thus
      is tested for its ability to utilize substrates mainly rich in protein components
      like beef extract and with successive production of electricity. The particular
      species has been found to generate a maximum power density of 85mW/m(2) and
      current density of ~270mA/m(2) using graphite felt as electrode. The maximum Open
      Circuit Voltage and current has been noted as 0.7Vand 0.8mA during these
      operational cycles. Cyclic voltammetry studies indicate the presence of some
      electroactive compounds which can facilitate electron transfer from bacteria to
      electrode. The number of electrogens able to generate electricity in mediator
      free conditions are few, and the study introduces more divergence to that
      population. Substrate specificity and electricity generation efficacy of the
      strain in treating wastewater, specially rich in protein content has been
      reported in the study. As the species has been found to be efficient in utilizing
      proteinaceous material, the technique can be useful to treat specific type of
      wastewaters like wastewater from slaughterhouses or from meat packaging industry.
      Treating them in a more economical way which generates electricity as a outcome
      must be preferred over the conventional aerobic treatments. Emphasizing on
      substrate specificity, the study introduces this novel Lysinibacillus strain as a
      potent biocatalyst and its sustainable role in MFC application for bioenergy
      generation. 

PMID- 24034434
TI  - Antioxidant defense system responses and role of nitrate reductase in the redox
      balance maintenance in Bradyrhizobium japonicum strains exposed to cadmium.
AB  - In this work, we evaluated the effects of cadmium (Cd) on the antioxidant defense
      system responses and the role of nitrate reductase (NR) in the redox balance
      maintenance in Bradyrhizobium japonicum strains. For that, B. japonicum USDA110
      and its NR defective mutant strain (GRPA1) were used. Results showed that the
      addition of 10MUM Cd did not modify the aerobic growth of the wild type strain
      while the mutant strain was strongly affected. Anaerobic growth revealed that
      only the parental strain was able to grow under this condition. Cd reduced
      drastically the NR activity in B. japonicum USDA110 and increased lipid peroxide
      content in both strains. Cd decreased reduced glutathione (GSH)/oxidized
      glutathione (GSSG) ratio in B. japonicum USDA110 although, a significant
      increased was observed in the mutant GRPA1. GSH-related enzymes were induced by
      Cd, being more evident the increase in the mutant strain. This different behavior
      observed between strains suggests that NR enzyme plays an important role in the
      redox balance maintenance in B. japonicum USDA 110 exposed to Cd. 

PMID- 24034435
TI  - Molecular and biochemical characterization of three GH62 alpha-l
      arabinofuranosidases from the soil deuteromycete Penicillium funiculosum.
AB  - Penicillium funiculosum is an industrial fungus exploited for its capacity to
      secrete a wide array of glycosyl hydrolases (GHs) and glycosyl transferases
      (GTs). These enzymes are part of an enzymatic cocktail that is commercialized
      under the name RovabioExcel((r)), which is used as feed additive in animal
      nutrition. The genome sequence of this filamentous fungus has revealed a
      remarkable richness in several accessory enzymes, and notably in alpha-l
      arabinofuranosidases (alpha-l-AFases) that participate in the hydrolysis of
      arabinoxylans (AX) in corn/wheat fibers used in poultry feed. Here, we report on
      the molecular and biochemical characterization of three GH62 family alpha-l
      AFases encoding genes in this filamentous fungus. Amino acids sequences showed
      strong similarities (>65%) between them, as well with GH62 enzymes from other
      filamentous fungi. Interestingly, one of the three PfABF62, namely PfABF62c is
      unique in bearing at its N-terminus a canonical family 1 carbohydrate-binding
      module (CBM1) of 37 amino acids length, which was shown to help the protein to
      bind to microcrystalline cellulose. Also, this PfABF62c showed optimal pH and
      temperature of 2.8 and 50 degrees C, respectively, whereas optimal activity for
      PfABF62a and PfABF62b were measured at 40 degrees C and at pH ranging between 2.6
      and 4.5. Arabinan and arabinoxylan, but no other sugars or polymers were found to
      augment the thermal transition of the three enzymes by 3-5 degrees C as measured
      by differential scanning fluorimetry. Finally, enzymatic hydrolysis fingerprints
      of heteroxylans allowed concluding that the mode of action of the GH62 enzymes
      from this fungal species was to remove arabinofuranosyl residues linked in
      position O-2 and O-3 of substituted xylose units in arabinoxylan chains. 

PMID- 24034436
TI  - Synthesis of nucleotide sugars and alpha-galacto-oligosaccharides by recombinant
      Escherichia coli cells with trehalose substrate.
AB  - Useful nucleoside diphosphate (NDP)-sugars and alpha-galacto-oligosaccharides
      were synthesized by recombinant Escherichia coli whole cells and compared to
      those produced by enzyme-coupling. Production yields of NDP-glucoses (Glcs) by
      whole cells harboring trehalose synthase (TS) were 60% for ADP-Glc, 82% for GDP
      Glc, and 27% for UDP-Glc, based on NDP used. Yield of UDP-galactose (Gal) by the
      whole-cell harboring a UDP-Gal 4-epimerase (pGALE) was 26% of the quantity of UDP
      Glc. alpha-Galacto-oligosaccharides, alpha-Gal epitope (Galalpha-3Galbeta-4Glu)
      and globotriose (Galalpha-4Galbeta-4Glu), were produced by the combination of
      three recombinant whole cells harboring TS, pGALE, and alpha
      galactosyltransferase, with production yields of 48% and 54%, based on UDP,
      respectively. Production yields of NDP-sugars and alpha-galacto-oligosaccharides
      by recombinant whole-cell reactions were approximately 1.5 times greater than
      those of enzyme-coupled reactions. These results suggest that a recombinant whole
      cell system using cells harboring TS with trehalose as a substrate may be used as
      an alternative and practical method for the production of NDP-sugars and alpha
      galacto-oligosaccharides. 

PMID- 24034437
TI  - Dietary intake of polyunsaturated fatty acids and fish among US children 12-60
      months of age.
AB  - This study aimed to estimate intake of individual polyunsaturated fatty acids
      (PUFAs), identify major dietary sources of PUFAs and estimate the proportion of
      individuals consuming fish among US children 12-60 months of age, by age and race
      and ethnicity. The study employed a cross-sectional design using US National
      Health and Nutrition Examination Survey data. Representative sample of US
      population based on selected counties. SUBJECTS: 2496 US children aged 12-60
      months. Mean daily intake of n-6 PUFAs and eicosapentaenoic acid (EPA) varied by
      age, with children 12-24 months of age having lower average intakes (mg or g day(
      1) ) than children 49-60 months of age and the lowest n6 : n3 ratio, upon
      adjustment for energy intake. Docosahexaenoic acid (DHA) intake was low (20 mg
      day(-1) ) compared to typical infant intake and did not change with age. Compared
      to non-Hispanic white children, Mexican American children had higher DHA and
      arachidonic acid (AA) intake. In the previous 30 days, 53.7% of children ever
      consumed fish. Non-Hispanic black children were more likely than non-Hispanic
      white children to have consumed fish (64.0% vs. 53.0%). Results indicate low
      prevalence of fish intake and key n-3 PUFAs, relative to n-6 fatty acids, which
      suggests room for improvement in the diets of US children. More research is
      needed to determine how increasing dietary intakes of n-3 PUFAs like DHA could
      benefit child health.

PMID- 24034438
TI  - Towards practical time-of-flight secondary ion mass spectrometry
      lignocellulolytic enzyme assays.
AB  - BACKGROUND: Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is a
      surface sensitive mass spectrometry technique with potential strengths as a
      method for detecting enzymatic activity on solid materials. In particular, ToF
      SIMS has been applied to detect the enzymatic degradation of woody
      lignocellulose. Proof-of-principle experiments previously demonstrated the
      detection of both lignin-degrading and cellulose-degrading enzymes on solvent
      extracted hardwood and softwood. However, these preliminary experiments suffered
      from low sample throughput and were restricted to samples which had been solvent
      extracted in order to minimize the potential for mass interferences between low
      molecular weight extractive compounds and polymeric lignocellulose components.
      RESULTS: The present work introduces a new, higher-throughput method for
      processing powdered wood samples for ToF-SIMS, meanwhile exploring likely sources
      of sample contamination. Multivariate analysis (MVA) including Principal
      Component Analysis (PCA) and Multivariate Curve Resolution (MCR) was regularly
      used to check for sample contamination as well as to detect extractives and
      enzyme activity. New data also demonstrates successful ToF-SIMS analysis of
      unextracted samples, placing an emphasis on identifying the low-mass secondary
      ion peaks related to extractives, revealing how extractives change previously
      established peak ratios used to describe enzyme activity, and elucidating peak
      intensity patterns for better detection of cellulase activity in the presence of
      extractives. The sensitivity of ToF-SIMS to a range of cellulase doses is also
      shown, along with preliminary experiments augmenting the cellulase cocktail with
      other proteins. CONCLUSIONS: These new procedures increase the throughput of
      sample preparation for ToF-SIMS analysis of lignocellulose and expand the
      applications of the method to include unextracted lignocellulose. These are
      important steps towards the practical use of ToF-SIMS as a tool to screen for
      changes in plant composition, whether the transformation of the lignocellulose is
      achieved through enzyme application, plant mutagenesis, or other treatments.

PMID- 24034439
TI  - Prediction of morbidity and mortality in patients with chronic hepatitis C by non
      invasive liver fibrosis models.
AB  - BACKGROUND & AIMS: Liver fibrosis is prognostic of outcomes among patients with
      chronic hepatitis C (CHC). We evaluated the accuracy of non-invasive markers and
      liver biopsy in predicting morbidity and mortality in CHC patients. METHODS:
      Compensated CHC patients were evaluated over a 10-year period. Non-invasive
      markers including Hepascore, FIB-4, APRI and liver biopsy results were
      retrospectively collated. Follow-up morbidity and mortality data were obtained
      from the Western Australian Data Linkage System. The prognostic significance of
      baseline non-invasive markers and biopsy were assessed using Kaplan-Meier
      analysis. RESULTS: A total of 406 subjects (64% male, mean age 48 +/- 11 years)
      were followed up for 2385 person-years, during which there were 22 (5.4%) deaths
      including 14 (3.4%) who died from liver disease or required liver
      transplantation. Sixteen (3.9%) subjects developed liver decompensation.
      Hepascore and liver biopsy (P < 0.005) but not APRI or FIB-4 were predictive of
      overall and liver-related mortality as well as liver decompensation. A
      Hepascore>0.5 was associated with increased overall mortality [Hazard Ratio
      (95%CI) 6.7 (2.6-17), P < 0.001], liver-related mortality [32.8 (4.3-250), P =
      0.001] and risk of future decompensation [11.8 (3.3-41), P < 0.001], whereas a
      Hepascore <=0.5 was associated with a 99% probability of not dying from liver
      related causes over 10 years. Hepascore had comparable accuracy with liver biopsy
      in predicting liver-related mortality with AUROC of 0.86 (95%CI 0.80-0.90) and
      0.87 (0.79-0.96), respectively. CONCLUSION: Hepascore is predictive of overall
      and liver-related mortality and morbidity in CHC patients with comparable
      accuracy to liver biopsy. Hepascore may be a useful prognostic marker in clinical
      practice.

PMID- 24034440
TI  - Measurement of rotational deformity: using a smartphone application is more
      accurate than conventional methods.
AB  - BACKGROUND: We assessed the accuracy of three different methods measuring the
      angle between two fixed Kirschner wires for the potential purpose of determining
      correction during rotational osteotomy of long bones. METHODS: Thirty-one
      orthopaedic consultants and registrars were prospectively asked to measure the
      angle between two fixed Kirschner wires in four saw bones models using three
      different techniques: visual estimation (VE), osteotomy templates (OT), and a
      contemporary smartphone (iPhone4; SP) with its gyroscopic function. These three
      methods were compared with the value obtained by computed tomography (CTV), which
      we considered the preferred value. RESULTS: For the pooled data for all four bone
      models, the mean difference of the VE compared with the CTV was 5.4 degrees  +/-
      5.3 degrees ; the mean difference of the OT compared with the CTV was 2.9 +/- 3.8
      degrees ; and the mean difference of the SP compared with the CTV was 0.8 +/- 0.9
      degrees . Using the pooled data, the difference between using each of these
      methods was highly significant, as demonstrated by the one-way analysis of
      variance across groups (P <= 0.001). In addition, for the pooled data the
      independent t-test between each pair of the three methods (VE and OT, VE and SP,
      and OT and SP) also demonstrated these differences were highly significant (P <=
      0.001) for all three comparisons. In this study, the number of years of
      orthopaedic experience did not significantly influence the ability of individual
      test subjects. CONCLUSION: Measurement of a rotational deformity using a SP app
      was significantly more accurate and consistent than both VE and OT. We believe
      the currently available SP technology provides orthopaedic surgeons with a
      significantly better alternative method of determining the magnitude of
      rotational deformity when performing corrective osteotomies.

PMID- 24034441
TI  - Fatigue loading and R-curve behavior of a dental glass-ceramic with multiple flaw
      distributions.
AB  - OBJECTIVES: To determine the effects of surface finish and mechanical loading on
      the rising toughness curve (R-curve) behavior of a fluorapatite glass-ceramic
      (IPS e.max ZirPress) and to determine a statistical model for fitting fatigue
      lifetime data with multiple flaw distributions. MATERIALS AND METHODS:
      Rectangular beam specimens were fabricated by pressing. Two groups of specimens
      (n=30) with polished (15 MUm) or air abraded surface were tested under rapid
      monotonic loading in oil. Additional polished specimens were subjected to cyclic
      loading at 2 Hz (n=44) and 10 Hz (n=36). All fatigue tests were performed using a
      fully articulated four-point flexure fixture in 37 degrees C water. Fractography
      was used to determine the critical flaw size and estimate fracture toughness. To
      prove the presence of R-curve behavior, non-linear regression was used. Forward
      stepwise regression was performed to determine the effects on fracture toughness
      of different variables, such as initial flaw type, critical flaw size, critical
      flaw eccentricity, cycling frequency, peak load, and number of cycles. Fatigue
      lifetime data were fit to an exclusive flaw model. RESULTS: There was an increase
      in fracture toughness values with increasing critical flaw size for both loading
      methods (rapid monotonic loading and fatigue). The values for the fracture
      toughness ranged from 0.75 to 1.1 MPam(1/2) reaching a plateau at different
      critical flaw sizes based on loading method. SIGNIFICANCE: Cyclic loading had a
      significant effect on the R-curve behavior. The fatigue lifetime distribution was
      dependent on the flaw distribution, and it fit well to an exclusive flaw model.

PMID- 24034443
TI  - Response to Loganathan et al. (2013): prolonged pudendal nerve terminal motor
      latency is associated with decreased resting and squeeze pressures in the intact
      anal sphincter.

PMID- 24034442
TI  - Impact of low-level gestational exposure to organophosphate pesticides on
      neurobehavior in early infancy: a prospective study.
AB  - BACKGROUND: National data suggest widespread gestational exposure to
      organophosphate pesticides (OPs) based on the detection of OP metabolites in the
      urine of pregnant women. Associations with early infant neurobehavior are largely
      understudied, with only two studies reporting abnormal reflexes in newborns in
      association with gestational exposure to OPs. Our objective was to utilize
      biological markers of OP metabolites in pregnant women and a comprehensive
      assessment of infant neurobehavior to determine the association of gestational
      exposure to OPs with neurobehavioral outcomes during early infancy. METHODS:
      Among a cohort of 350 mother/infant pairs, we measured six common
      dialkylphosphate metabolites of OP pesticides in maternal urine, at two times
      during pregnancy (16 w & 26 w gestation), then calculated aggregate
      concentrations of diethylphosphate, dimethylphosphate, and total dialkyphosphate
      metabolites. We measured infant neurobehavior at about five weeks of age using
      the NICU Network Neurobehavioral Scale (NNNS), a comprehensive assessment of
      neurobehavior in young infants. Analyses of associations between gestational
      exposure to OPs and neurobehavior at five weeks included multiple linear and
      logistic regression. RESULTS: After adjustment for covariates, higher creatinine
      corrected urinary concentrations of diethylphosphate metabolites were associated
      with improved attention and reduced lethargy and hypotonia in young infants.
      Higher creatinine-corrected urinary concentrations of total dialkylphosphate
      metabolites were associated with fewer signs of autonomic stress. Women who were
      white, married, had advanced education, and reported more frequent consumption of
      fresh fruits and vegetables had higher concentrations of OP metabolites during
      pregnancy. CONCLUSIONS: In this sample of pregnant women whose urinary
      concentrations of dialkylphosphate metabolites are representative of national
      exposure levels, we found no detrimental effects of gestational exposure to OPs
      on neurobehavioral outcomes among young infants. These results are important as
      they suggest there may be minimal to no detectable adverse impact of low level
      prenatal OP exposure on the neurobehavior of young infants.

PMID- 24034444
TI  - Reproductive tradeoff limits the predatory efficiency of female Arizona Bark
      Scorpions (Centruroides sculpturatus).
AB  - BACKGROUND: Life history tradeoffs may result from temporal and physiological
      constraints intrinsic to an organism. When faced with limited time and energy,
      compromises occur and these resources are allocated among essential activities,
      such as body growth, maintenance, foraging, mating, and offspring care. We
      investigated potential tradeoffs that may occur between reproductive activities
      and feeding performance in female Arizona Bark Scorpions (Centruroides
      sculpturatus) by comparing the time taken to capture prey between non
      reproductive and reproductive females (gravid females and females exhibiting
      maternal care, i.e. carrying offspring on their backs). RESULTS: Gravid females
      were as efficient at catching prey as non-gravid females. To control for
      variation in the duration of the maternal care period, we removed all offspring
      from all post-parturient females after 5 days. Brooding females and females 24
      hours following offspring removal (FOR) did not successfully capture prey within
      the 900-second trial period. Twenty-eight days FOR, females caught prey faster
      than females displaying maternal care and females 24 hours FOR, but were not as
      efficient at catching prey as non-gravid and gravid females. When pursuing prey,
      C. sculpturatus exhibiting maternal care used an active foraging strategy more
      frequently than non-gravid, gravid, and females 28 days FOR. In contrast, non
      gravid, gravid, and females 28 days FOR used active and ambush foraging with
      similar frequency. CONCLUSIONS: Our data suggest that reproduction does not
      significantly reduce the predatory efficiency of gravid C. sculpturatus, and that
      these females can cope with increasing body mass and the physiological costs of
      gestation. However, the observation that brooding females and females 24 hours
      FOR did not catch prey within the trial period indicates that maternal care
      significantly reduces predatory efficiency in these scorpions. Females 28 days
      FOR were still not as efficient at catching prey as non-gravid and gravid
      females, suggesting that reproductive costs extend for at least 4 weeks after the
      end of the maternal care period. Preferential use of an active foraging strategy
      by brooding females may increase prey encounter rates, allowing the scorpions to
      more rapidly replenish energy reserves depleted during reproduction. However,
      active foraging may be energetically costly and increase predation risk for
      brooding females. Our findings regarding antagonistic interactions between
      reproduction and feeding in female C. sculpturatus demonstrate the pervasive
      nature of reproductive costs for viviparous females, and may provide insight on
      factors that influence the diversity of reproductive strategies observed in
      nature.

PMID- 24034445
TI  - The significance of clinical margins in CO2 laser resected laryngeal squamous
      cell carcinoma and its impact on disease management: our experience in twenty
      nine patients.

PMID- 24034447
TI  - Kleine-Levin syndrome and bipolar disorder: a differential diagnosis of recurrent
      and resistant depression.
AB  - OBJECTIVES: Kleine-Levin syndrome (KLS) is a rare sleep disorder (1-2 reported
      cases per one million individuals) primarily affecting young subjects. Episodes
      are characterized by hypersomnia, cognitive impairment, feelings of
      derealization, and, less frequently, hyperphagia (66%), hypersexuality [53%
      (principally men)], and depressed mood [53% (predominantly women)]. KLS cases are
      frequently misdiagnosed and pose therapeutic challenges (i.e., amantadine and
      mood stabilizers are only marginally effective). The cause of KLS is unknown, but
      an association between KLS and mood disorders has been suggested by some clinical
      analogies. METHODS: We report the case of a 44-year-old Caucasian woman with
      bipolar I disorder referred by her psychiatrist to our psychiatric center for
      recurrent and resistant major depression according to DSM-IV-TR criteria.
      RESULTS: Following examination, we confirmed the diagnoses of bipolar I disorder
      and KLS. The patient experienced about 15 evenly distributed KLS episodes, each
      lasting about one week, which occurred during the six years following her first
      manifestation at age 18 years. An electroencephalogram was performed during a KLS
      episode and showed high-amplitude theta waves in the left and right temporal
      lobes, with predominance in the left hemisphere. The pronounced bipolar disorder
      symptomatology, starting at 15 years of age with major depression and a suicide
      attempt, had impeded the identification of KLS, which was not diagnosed until the
      age of 42. CONCLUSIONS: Bipolar disorder may obscure KLS, with each condition
      adversely affecting the course of the other, and consequently, the co-occurrence
      of KLS and bipolar disorder may be underestimated. KLS and bipolar disorder may
      share common vulnerability factors, such as immune-inflammatory and circadian
      disturbances, and there may be a genetic predisposition for both. Additionally,
      mood stabilizers may be effective for KLS and bipolar disorder.

PMID- 24034446
TI  - Homology modeling and ligand docking of Mitogen-activated protein kinase
      activated protein kinase 5 (MK5).
AB  - BACKGROUND: Mitogen-activated protein kinase-activated protein kinase 5 (MK5) is
      involved in one of the major signaling pathways in cells, the mitogen-activated
      protein kinase pathway. MK5 was discovered in 1998 by the groups of Houng Ni and
      Ligou New, and was found to be highly conserved throughout the vertebrates.
      Studies, both in vivo and in vitro, have shown that it is implicated in tumor
      suppression as well as tumor promotion, embryogenesis, anxiety, locomotion, cell
      motility and cell cycle regulation. METHODS: In order to obtain a molecular model
      of MK5 that can be used as a working tool for development of chemical probes,
      three MK5 models were constructed and refined based on three different known
      crystal structures of the closely related MKs; MK2 [PDB: 2OZA and PDB: 3M2W] and
      MK3 [PDB: 3FHR]. The main purpose of the present MK5 molecular modeling study was
      to identify the best suited template for making a MK5 model. The ability of the
      generated models to effectively discriminate between known inhibitors and decoys
      was analyzed using receiver operating characteristic (ROC) curves. RESULTS:
      According to the ROC curve analyzes, the refined model based on 3FHR was most
      effective in discrimination between known inhibitors and decoys. CONCLUSIONS: The
      3FHR-based MK5 model may serve as a working tool for development of chemical
      probes using computer aided drug design. The biological function of MK5 still
      remains elusive, but its role as a possible drug target may be elucidated in the
      near future.

PMID- 24034448
TI  - Genetic factors in exercise adoption, adherence and obesity.
AB  - Physical activity and exercise play critical roles in energy balance. While many
      interventions targeted at increasing physical activity have demonstrated efficacy
      in promoting weight loss or maintenance in the short term, long term adherence to
      such programmes is not frequently observed. Numerous factors have been examined
      for their ability to predict and/or influence physical activity and exercise
      adherence. Although physical activity has been demonstrated to have a strong
      genetic component in both animals and humans, few studies have examined the
      association between genetic variation and exercise adherence. In this review, we
      provide a detailed overview of the non-genetic and genetic predictors of physical
      activity and adherence to exercise. In addition, we report the results of
      analysis of 26 single nucleotide polymorphisms in six candidate genes examined
      for association to exercise adherence, duration, intensity and total exercise
      dose in young adults from the Training Interventions and Genetics of Exercise
      Response (TIGER) Study. Based on both animal and human research, neural
      signalling and pleasure/reward systems in the brain may drive in large part the
      propensity to be physically active and to adhere to an exercise programme.
      Adherence/compliance research in other fields may inform future investigation of
      the genetics of exercise adherence. 

PMID- 24034449
TI  - Samples from subdivided populations yield biased estimates of effective size that
      overestimate the rate of loss of genetic variation.
AB  - Many empirical studies estimating effective population size apply the temporal
      method that provides an estimate of the variance effective size through the
      amount of temporal allele frequency change under the assumption that the study
      population is completely isolated. This assumption is frequently violated, and
      the magnitude of the resulting bias is generally unknown. We studied how gene
      flow affects estimates of effective size obtained by the temporal method when
      sampling from a population system and provide analytical expressions for the
      expected estimate under an island model of migration. We show that the temporal
      method tends to systematically underestimate both local and global effective size
      when populations are connected by gene flow, and the bias is sometimes dramatic.
      The problem is particularly likely to occur when sampling from a subdivided
      population where high levels of gene flow obscure identification of subpopulation
      boundaries. In such situations, sampling in a manner that prevents biased
      estimates can be difficult. This phenomenon might partially explain the
      frequently reported unexpectedly low effective population sizes of marine
      populations that have raised concern regarding the genetic vulnerability of even
      exceptionally large populations. 

PMID- 24034450
TI  - Evaluation of the profibrinolytic properties of a bispecific antibody-based
      inhibitor against human and mouse thrombin-activatable fibrinolysis inhibitor and
      plasminogen activator inhibitor-1.

PMID- 24034451
TI  - Quality of obstetric care in the sparsely populated sub-arctic area of Norway
      2009-2011.
AB  - BACKGROUND: It is challenging to obtain high quality obstetric care in a sparsely
      populated area. In the subarctic region of Norway, significant distances, weather
      conditions and seasonable darkness have called for a decentralized care model. We
      aimed to explore the quality of this care. METHODS: A retrospective study
      employing data (2009-11) from the Medical Birth Registry of Norway was initiated.
      Northern Norwegian and Norwegian figures were compared. Midwife administered
      maternity units, departments at local and regional specialist hospitals were
      compared. National registry data on post-caesarean wound infection (2009-2010)
      was added. Quality of care was measured as rate of multiple pregnancies,
      caesarean section, post-caesarean wound infection, Apgar score <7, birth weight
      <2.5 kilos, perineal rupture, stillbirth, eclampsia, pregnancy induced diabetes
      and vacuum or forceps assisted delivery. There were 15,586 births in 15 delivery
      units. RESULTS: Multiple pregnancies were less common in northern Norway (1.3 vs.
      1.7%) (P = 0.02). Less use of vacuum (6.6% vs. 8.3%) (P = 0.01) and forceps (0.9%
      vs 1.7%) (P < 0.01) assisted delivery was observed. There was no difference with
      regard to pregnancy induced diabetes, caesarean section, stillbirth, Apgar score
      < 7 and eclampsia. A significant difference in birth weight < 2.5 kilos (4.7% vs.
      5.0%) (P < 0.04) and perineal rupture grade 3 and 4 (1.5% vs. 2.3%) (P < 0.02)
      were revealed. The post-caesarean wound infection rate was higher (10.5% vs.
      7.4%) (P < 0.01). CONCLUSION: Northern Norway had an obstetric care of good
      quality. Birth weight, multiple pregnancies and post-caesarean wound infection
      rates should be further elucidated.

PMID- 24034453
TI  - Burns in children: standard and new treatments.
AB  - Outcomes of patients with burns have improved substantially over the past two
      decades. Findings from a 2012 study in The Lancet showed that a burn size of more
      than 60% total body surface area burned (an increase from 40% a decade ago) is
      associated with risks and mortality. Similar data have been obtained in adults
      and elderly people who have been severely burned. We discuss recent and future
      developments in burn care to improve outcomes of children. 

PMID- 24034454
TI  - [Anti-Hu antibodies: a remarkable immulogical phenotype for several
      paraneoplastic syndromes].

PMID- 24034455
TI  - [Pulmonary diseases and non-amyloid light chain deposition].

PMID- 24034452
TI  - Dengue 2 infection of HepG2 liver cells results in endoplasmic reticulum stress
      and induction of multiple pathways of cell death.
AB  - BACKGROUND: A number of studies have implicated the direct involvement of the
      liver in dengue virus (DENV) infection, and it has been widely shown that liver
      cells subsequently undergo apoptosis. The mechanism by which liver cells undergo
      apoptosis in response to DENV infection remains unclear. To provide further
      information on the mechanism of apoptosis in DENV infected liver cells, HepG2
      cells were infected with DENV 2 and analyzed for the induction of ER stress,
      apoptosis and autophagy. RESULTS: In response to DENV infection, HepG2 cells
      showed the induction of both the ER resident unfolded protein response as well as
      the Noxa/PUMA stress response pathways. Proteolytic activation of caspases 4, 7,
      8 and 9 was observed as well as changes in mitochondrial transmembrane potential.
      Increased monodansylcadaverine staining was observed in DENV infected cells,
      consistent with the previously reported induction of autophagy. CONCLUSIONS:
      These results are consistent with a model in which the induction of multiple ER
      stress pathways is coupled with the induction of multiple cell death pathways as
      a mechanism to ensure the removal of infected liver cells from the system.

PMID- 24034456
TI  - [Lung cancer in nonsmoker: a separate entity].

PMID- 24034457
TI  - [Hospital undertaking of patients with a resection of lung cancer].
AB  - INTRODUCTION: The aim of the study is to describe the hospital management of
      patients undergoing pulmonary resection for lung cancer in France. METHODS: Data
      from patients who underwent resection for "malignant neoplasm of bronchus and
      lung" in 2008 were analyzed from French PMSI database. Hospitalizations,
      chemotherapy and radiotherapy sessions were analyzed one year before and after
      the procedure. RESULTS: In 2008, 9161 patients were hospitalized for a resection
      of lung tumor. Sex ratio was 2.8 (n=6736 men) and average age was 62.8 years.
      During hospitalization for surgery, 3.5% of patients (n=323) died. In the year
      before the procedure, 10% of patients (n=961) received neoadjuvant chemotherapy
      (mean number: 5.2 sessions per patient). In the year after the procedure, 41% of
      patients (n=3796) received adjuvant chemotherapy (6.6 sessions per patient), 9%
      (n=812) received adjuvant radiotherapy (16.8 sessions per patient), 6% (n=562)
      were re-hospitalized for surgery for an additional procedure. CONCLUSION: In
      France, pulmonary resection for lung cancer was associated for about half of
      patients in a multimodal treatment with combination between chemotherapy and/or
      radiotherapy.

PMID- 24034458
TI  - [Epidemiology and incidence of primary lung cancer in a region with low tobacco
      consumption: Guadeloupe (French West Indies). Data from the cancer registry 2008
      2009].
AB  - INTRODUCTION: Few data are available about primary lung cancer in the Caribbean.
      The purpose of this study was to provide, for the first time, the epidemiological
      and clinical characteristics of primary lung cancer in the archipelago of
      Guadeloupe (French West Indies). METHODS: From the cancer registry, we identified
      in this retrospective study, all incident cases of primary lung cancer that had
      occurred between 1st January 2008 and 31st December 2009 in Guadeloupe. RESULTS:
      Over the period from 2008 to 2009, 106 patients with primary lung cancer were
      identified. Males accounted for 72.6% and the women for 27.4%. Mean incidence
      rate over the 2 years was estimated at 13.4/100000 persons-years (95% CI: [6.0
      20.8]) in men (world standardized) and 4.2/100000 persons-years (95% CI: [0.3
      8.1]) in women. The median age at initial diagnosis was 65 years for men and 66
      years for women. We noted a proportion of 61.3% of current smokers, 4.7% of
      passive smokers and 34% of non-smokers. The comorbidities were present in 41% of
      patients. Non-small cell lung cancer (NSCLC) accounted for 88.7% of lung cancers
      and small cell lung cancer for 7.5%. The most common histological type was
      adenocarcinoma (43%) followed by squamous cell (24%). Stage III and IV patients
      accounted for 64.1% of individuals with NSCLC. CONCLUSION: The incidence of
      primary lung cancer in Guadeloupe is relatively low compared to metropolitan
      France. Guadeloupe is also a French department where the rate of tobacco
      consumption is one of the lowest.

PMID- 24034460
TI  - [The indoor sport: is it a risk factor for allergic rhinitis?].
AB  - INTRODUCTION: The high prevalence of allergic rhinitis that occurs in elite
      athletes has been extensively investigated. However, data among recreational
      athletes practicing indoor activities remain contradictory. The aim of the
      present study was to determine whether taking part in gym based sporting
      activities constitutes a risk factor for allergic rhinitis in recreational
      athletes. METHODS: A group of 50 recreational athletes was examined. A specific
      questionnaire for the screening of allergic rhinitis and a battery of skin prick
      tests to aeroallergens were administered to each participant. Measurements of
      nasal symptoms, peak nasal inspiratory flow (PNIF) and lung function were also
      obtained before and after a training session. RESULTS: Thirty-two percent of the
      participants were atopic, 18% suffered from allergic rhinitis. This prevalence is
      similar to that of the general population (16.9%). After exercise, nasal symptom
      prevalence did not change significantly. However, an improvement in nasal
      inspiratory flow was observed in 70% of the participants. No statistically
      significant change in lung function was noticed. CONCLUSIONS: Our results showed
      that the occasional practice of sport in the gyms does not constitute a risk
      factor for atopy or allergic rhinitis. However, this kind of activity induces an
      increase in the nasal patency of both the healthy and the rhinitic subjects.

PMID- 24034459
TI  - [Correlation of the manifestations of tuberculosis and the degree of
      immunosuppression in patients with HIV].
AB  - CONTEXT: Correlation of the manifestations of tuberculosis and the degree of
      immunosuppression in patients with HIV. BACKGROUND: The advent of HIV has
      contributed to the increase in the number of people with tuberculosis. The
      clinical and paraclinical of TB/HIV co-infected are polymorphic and function of
      immune status. OBJECTIVES: To determines the clinical and paraclinical
      characteristics of TB related to different levels of CD4 lymphocytes.
      METHODOLOGY: A retrospective case series based on analysis of 450 patients with
      both TB/HIV co-infections. It focused on the records of patients with pulmonary
      smear-positive (TPM +) with a positive HIV status. The effect of
      immunosuppression was analyzed in groups based on the CD4 count (<200/mm(3), of
      200-350/mm(3) and>350/mm(3)), in a chronological fashion from April to September
      2010 until there were 150 patients in each CD4 group. RESULTS: Among the 450
      patients, 71.1% were between 25 and 45years old. The clinical signs were more
      significant as the level of CD4 fell. The clinical signs were predominantly fever
      (93%) and weight loss (62.7%). Pulmonary cavitation (59.3%), infiltrates (38.7%)
      and the location of the lesions at the lung apex (72%) were more common in the
      third group patients. By contrast, extra pulmonary lesions (mediastinal
      lymphadenopathy, pleurisy) and normal x-ray (9.3%) were more frequent in patients
      of the first group. The scarcity of cavitations (22.3% compared to 59.3% CD4>350)
      and the increase in associated lesions became more marked if patients were
      immunocompromised. Hematologic, hepatic, renal disorders were more frequent and
      severe in the most immunocompromised patient group. CONCLUSION: HIV-associated
      tuberculosis has an atypical clinical, radiological, biological presentation and
      is more severe when there is significant immunosuppression.

PMID- 24034461
TI  - [Anti-Hu antibody syndrome: diagnostic and therapeutic difficulties].
AB  - INTRODUCTION: Anti-Hu antibody syndrome is a paraneoplastic syndrome usually
      associated with small cell lung carcinoma which induces various symptoms,
      particularly neurological ones. CASE REPORT: We describe the case of a 49-year
      old woman with a small cell lung carcinoma who initially experiences a
      spontaneous regression but then developed neurological symptoms associated with
      severe autonomic dysfunction manifesting as chronic intestinal pseudo-obstruction
      and leading finally to hemodynamic failure. CONCLUSION: Anti-Hu antibody syndrome
      remains a rare entity. Its diagnosis must be considered in the face of neurologic
      symptoms associated with small cell lung cancer.

PMID- 24034462
TI  - [An unusual cause of cystic lung disease: light chain deposition disease].
AB  - INTRODUCTION: Light chain deposition disease is a rare clinical entity
      characterized by deposition of monoclonal immunoglobulin light chains in organs.
      The kidneys are almost always affected, while the lung manifestations that have
      been reported, including nodular or diffuse disease, especially cystic lesions,
      are unusual. CASE REPORT: We report the case of a 60-year-old man with a diffuse
      infiltrative lung disease characterized by numerous apical cysts. The diagnosis
      of light chain deposition cystic lung disease was obtained by surgical lung
      biopsy. Light chain deposits in the salivary glands were the only extrapulmonary
      manifestation. Despite 12 chemotherapy cycles, the patient's lung function and
      radiological appearances worsened. CONCLUSION: This is the fourth case describing
      a cystic lung disease due to light chain deposition in the literature. It
      highlights the need for comprehensive investigations so as not to miss this rare
      cause of cystic lung disease, which appears to be related to a primary pulmonary
      lymphoproliferative disorder. The only treatment that appears to be effective is
      lung transplantation.

PMID- 24034463
TI  - [Biological diagnosis of resistance to erlotinib in a malignant pleural
      effusion].
AB  - INTRODUCTION: The characterization of genetic abnormalities in non-small cell
      lung cancer (NSCLC) constitutes a theranostic revolution which is leading to
      rapid progress in the personalized management of this condition. CASE REPORT: We
      present the case of a patient with NSCLC harboring an activating mutation of the
      Epidermal Growth Factor Receptor (EGFR). After two years of treatment with a
      tyrosine kinase inhibitor (TKI), the development of a pleural effusion
      demonstrated that the NSCLC had progressed. The T790M mutation was identified in
      tumour cells from the pleural aspirate. This anomaly had not been observed in the
      initial lung biopsy sample. CONCLUSION: The genetic study of tumour cells
      contained in a biological fluid could be used to initiate molecular monitoring of
      the NSCLC tumour, without requiring repeated tissue biopsies and to customize the
      treatment in some patients with NSCLC.

PMID- 24034464
TI  - [Lung cancer in never smokers: a French national cohort (BioCAST/IFCT-1002)].
AB  - Around 5 to 25% of lung cancer worldwide occurs in lifelong non-smokers (less
      than 100 cigarettes in lifetime). Lung cancer in never smokers (LCINS) shows many
      clinical, epidemiological and molecular differences compared to those related to
      tobacco. It is therefore often considered as a separate entity. LCINS is also a
      good model for the study of lung cancer risk factors and tumoral mutation
      profiles (usually more common and specific). However, most data has come from
      retrospective studies and/or from Asian populations, although this disease shows
      high geographic lability. The BioCAST/IFCT-1002 is a national, multicentric,
      prospective study promoted by the French intergroup IFCT. The first objective is
      to describe the clinical and molecular epidemiology of LCINS in a French
      population. Detailed data (including exposure to many risk factors) are collected
      directly from the patient through a standardized questionnaire completed during a
      telephone interview. All patients also undergo blood sampling for the analysis of
      genomic polymorphisms and the characterization of epigenetic anomalies. BioCAST
      hopes to provide concrete answers for clinicians and patients about this entity. 

PMID- 24034465
TI  - Differential DNA methylation with age displays  both common and dynamic features
      across  human tissues that are influenced by CpG  landscape.
AB  - BACKGROUND: DNA methylation is an epigenetic modification that changes with age
      in human tissues, although the mechanisms and specificity of this process are
      still poorly understood. We compared CpG methylation changes with age across 283
      human blood, brain, kidney, and skeletal muscle samples using methylation arrays
      to identify tissue-specific age effects. RESULTS: We found age-associated CpGs
      (ageCGs) that are both tissue-specific and common across tissues. Tissue-specific
      age CGs are frequently located outside CpG islands with decreased methylation,
      and common ageCGs show the opposite trend. AgeCGs are significantly associated
      with poorly expressed genes, but those with decreasing methylation are linked
      with higher tissue-specific expression levels compared with increasing
      methylation. Therefore, tissue-specific gene expression may protect against
      common age-dependent methylation. Distinguished from other tissues, skeletal
      muscle age CGs are more associated with expression, enriched near genes related
      to myofiber contraction, and closer to muscle-specific CTCF binding sites. Kidney
      specific ageCGs are more increasingly methylated compared to other tissues as
      measured by affiliation with kidney-specific expressed genes. Underlying
      chromatin features also mark common and tissue-specific age effects reflective of
      poised and active chromatin states, respectively. In contrast with decreasingly
      methylated ageCGs, increasingly methylated ageCGs are also generally further from
      CTCF binding sites and enriched within lamina associated domains. CONCLUSIONS:
      Our data identified common and tissue-specific DNA methylation changes with age
      that are reflective of CpG landscape and suggests both common and unique
      alterations within human tissues. Our findings also indicate that a simple
      epigenetic drift model is insufficient to explain all age-related changes in DNA
      methylation.

PMID- 24034466
TI  - Change to either a nonandrogenic or androgenic progestin-containing oral
      contraceptive preparation is associated with improved sexual function in women
      with oral contraceptive-associated sexual dysfunction.
AB  - INTRODUCTION: It is a commonly held belief that combined oral contraceptive (COC)
      pills containing an androgenic progestin may be less likely to impair sexual
      function than COCs containing an anti-androgenic progestin. AIM: The study aims
      to compare the effects of a COC containing a progestin with an anti-androgenic
      profile (estradiol valerate [E2 V]/dienogest [DNG]) to that of one with an
      androgenic progestin (ethinyl estradiol [EE]/levonorgestrel [LNG]) on sexual
      function in women with COC-associated sexual dysfunction. METHODS: In this
      multicenter, randomized, double-blind, noninferiority study, women with COC
      associated female sexual dysfunction (FSD) were randomized to E2 V/DNG or EE/LNG
      for six cycles. The primary outcome was the change in the sum of Female Sexual
      Function Index (FSFI) desire and arousal component scores between baseline and
      cycle 6. Secondary outcome measures included changes to the FSFI domains, the
      Female Sexual Distress Scale (FSDS-R), Vaginal Health Assessment, the Atrophy
      Symptom Questionnaire, and the Psychological General Well Being Index over six
      treatment cycles. MAIN OUTCOME MEASURE: The main outcome is the change in the sum
      of FSFI desire and arousal component scores between baseline and cycle 6.
      RESULTS: Of 276 women screened, 213 received treatment and 191 completed the
      study. The mean increase in the sum of FSFI desire and arousal component scores
      was 5.90 (standard deviation [SD] 5.45) for E2 V/DNG and 5.79 (SD 6.17) for
      EE/LNG (change from baseline P < 0.0001, both groups). Both treatments showed
      equal efficacy and were associated with improvements in all domains of the FSFI,
      with no between-group differences. Both COCs reduced the distress associated with
      FSD, as indicated by reduced FSDS-R scores. CONCLUSION: In women with COC
      associated FSD, switching to either E2 V/DNG or EE/LNG was associated with
      equivalent improvements in symptoms, challenging the perception that COCs
      containing anti-androgenic progestins have a detrimental effect on sexual
      function relative to those containing androgenic progestins.

PMID- 24034467
TI  - The Academy celebrates its 40(th) anniversary.

PMID- 24034468
TI  - History counts: how history can shape our understanding of health policy.
AB  - Historians of nursing can inform and provide perspective and context to the
      discipline and to policy makers. This article provides several examples of the
      interplay of history and health policy debates across time and place. From issues
      of the nursing workforce to discussions about the skill level needed to safely
      care for patients and the issues of practice boundaries, history provides
      evidence for shaping our understanding of and engagement with health policy.
      History offers a way to understand the present and think about the future. It
      illustrates a critical perspective for both action and advocacy.

PMID- 24034470
TI  - A nursing historical perspective on the medical home: impact on health care
      policy.
AB  - BACKGROUND: The idea of a "medical home" is rapidly gaining in popularity in
      health policy circles today. In the face of a shortage of primary care
      physicians, it has led to a national debate about who should lead the homes, who
      should deliver care, the kind of care that should be offered, and the location of
      that care. A historical examination of nurses' role in primary care can provide
      evidence to inform the current dialogue. PURPOSE: This article provides insight
      into nursing's role in primary health care during the early 20th century.
      METHODS: Traditional historical methods were used. DISCUSSION/CONCLUSIONS: Three
      historical case studies provide evidence of how nursing and medicine worked
      together in the past and informs the discussion about using nurses to deliver
      primary health care today. Policy makers should not overlook the central role
      nurses have long played in providing access to care for numerous underserved
      populations. Makers should not overlook the central role nurses have long played
      in providing access to care for numerous underserved populations.

PMID- 24034469
TI  - "All who nurse for hire": nursing and the mixed legacy of legislative victories.
AB  - Sustained support of policy initiatives by nursing has resulted in significant
      legislative victories. One victory, the passage of the 1938 New York State Todd
      Feld Act, which underwent legislative debate at a time when the nurse labor
      market was in disarray, during an economic depression, and before U.S. entry into
      World War II, reinforces our understanding that nursing must be a strong shepherd
      for policies beneficial for health care delivery. Designed to correct serious
      deficiencies in the nursing workforce, the act successfully required licensing
      for those working as registered and practical nurses. Yet, its provisions failed
      to stop all unlicensed nurse workers from practicing. Rapid changes occurring in
      the nurse labor market against the backdrop of growing hospital power over the
      employment of all nurse workers minimized the act's effectiveness. Policy
      implications include the need to focus on the complex nature of health care
      policy initiatives, flexibility in the face of changing circumstances, and
      acceptance of political realities.

PMID- 24034471
TI  - The role of Catholic nurses in women's health care policy disputes: a historical
      study.
AB  - BACKGROUND: The Catholic Church oversees the nation's largest group of not-for
      profit health care facilities, and in certain areas a Catholic hospital is the
      only hospital available. Recently, Catholic hospitals' provision of health care
      services to women in the areas of reproductive procedures has come under
      scrutiny. PURPOSE: This article examines the role of Catholic sister nurses in
      health policy for women. METHODS: Using historical analysis, this article focuses
      on the tensions between Catholic religious priests and sister nurses over access
      to health care. DISCUSSION: A historical examination of Catholic hospitals'
      influence on health policy offers a vehicle to contemplate the role that religion
      plays in the area of women's health. CONCLUSION: Catholic sister nurses used the
      Catholic Church's organizational power to influence health policy that affected
      their hospitals. However, they exercised due restraint in their advocacy efforts,
      always having to be mindful of ecclesiastical barriers they could not abridge,
      particularly those that pertained to reproduction. This has significantly
      affected health policy for women.

PMID- 24034472
TI  - Assessment of shock index in healthy dogs and dogs in hemorrhagic shock.
AB  - OBJECTIVE: To compare the shock index (SI) in a population of healthy dogs to a
      population of dogs with confirmed hemorrhagic shock. DESIGN: Retrospective
      analysis of data collected prospectively from 2 previous studies. SETTING:
      University teaching hospital. ANIMALS: Seventy-eight healthy control dogs
      enrolled in a study to establish a reference interval for a tissue oxygen
      monitor; 38 dogs with confirmed hemorrhagic shock enrolled in a study to evaluate
      the tissue oxygen monitor in hemorrhagic shock. The heart rate and systolic blood
      pressure obtained during the respective studies were used to calculate the SI.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Shock index was significantly
      higher in the hemorrhage group (median 1.37, range 0.78-4.35) than the control
      group (median 0.91, range 0.57-1.53); 92% of the dogs in hemorrhagic shock had an
      SI of >0.91. Compared with controls, dogs in hemorrhagic shock had significantly
      lower body temperatures (median 38.3 degrees C, range 35.6-39.9 degrees C versus
      median 38.7 degrees C, range 37.5-39.9 degrees C), higher heart rates (median
      150/min, range 120-220/min versus median 110/min range 80-150/min), lower
      systolic blood pressures (mean 112 mm Hg, SD +/-35.8 mm Hg versus mean 125 mm Hg,
      SD +/-21.5 mm Hg), higher lactate concentrations (median 0.51 mmol/L, range 0.078
      1.41 mmol/L versus median 0.11 mmol/L, range 0.033-0.33 mmol/L), and lower
      hemoglobin concentrations (median 81 g/L, range 56-183 g/L versus median 162.5
      g/L, range 133-198 g/L). CONCLUSIONS: Shock index is a simple and easy
      calculation that can be used as an additional triage tool and should prompt
      further investigation for hemorrhage if the values are >0.9.

PMID- 24034473
TI  - Prospective memory impairment and its implications for community living skills in
      bipolar disorder.
AB  - OBJECTIVE: Prospective memory (PM) refers to the ability to undertake intended
      actions in the future. The functional significance of PM in bipolar disorder (BD)
      has not yet been investigated. This study examined PM impairment and its role in
      community living skills in clinically stable individuals with BD. METHODS:
      Seventy-six individuals with BD and 44 healthy individuals were assessed with the
      Chinese version of the Cambridge Prospective Memory Test. Socio-demographic
      characteristics, retrospective memory (RM; the ability to recall or recognize
      past information), and intelligence were also measured in all participants. The
      clinical condition and community living skills of patients with BD were rated
      independently with standardized instruments. RESULTS: Patients with BD showed PM
      impairment and their PM total scores independently predicted the level of
      community living skills in regression analyses. In follow-up analyses, the
      contribution was found to be accounted for by the time-based PM scores.
      CONCLUSIONS: Given the expanding body of research on the utility of PM in
      predicting functioning, these findings further support the role of PM in
      community living skills in individuals with BD. The results suggest that PM
      training might be an integral part of clinical rehabilitation devised for
      individuals with BD.

PMID- 24034474
TI  - Best practice in alien species risk assessment: a comment on Leung et al. (2012).
AB  - The TEASI model is presented in Leung et al. (2012; TEASIng apart alien species
      risk assessments: a framework for best practices. Ecol. Lett., 15, 1475) as a
      framework for best practice in alien species risk assessment. This is not
      supported by the paper's review as it does not define good, bad or best practice
      and therefore cannot logically make this claim. 

PMID- 24034475
TI  - Proteomics methods for subcellular proteome analysis.
AB  - The elucidation of the subcellular distribution of proteins under different
      conditions is a major challenge in cell biology. This challenge is further
      complicated by the multicompartmental and dynamic nature of protein localization.
      To address this issue, quantitative proteomics workflows have been developed to
      reliably identify the protein complement of whole organelles, as well as for
      protein assignment to subcellular location and relative protein quantification
      based on different cell culture conditions. Here, we review quantitative MS-based
      approaches that combine cellular fractionation with proteomic analysis. The
      application of these methods to the characterization of organellar composition
      and to the determination of the dynamic nature of protein complexes is improving
      our understanding of protein functions and dynamics. 

PMID- 24034476
TI  - Small bowel obstruction following laparoscopic ventral mesh rectopexy.

PMID- 24034477
TI  - Making progress on the WHO Public Health Research Agenda for Influenza.

PMID- 24034480
TI  - Brief literature review for the WHO global influenza research agenda--highly
      pathogenic avian influenza H5N1 risk in humans.
AB  - Highly pathogenic avian influenza A H5N1 viruses remain a significant health
      threat to humans given the continued rare occurrence of human cases with a high
      case fatality rate. This brief literature review summarizes available evidence of
      risk factors for H5N1 infection in humans and updates a recent systematic review
      published in early 2011. Several epidemiologic studies have been published to
      evaluate the risk factors for H5N1 infection in humans, including contact with
      poultry and poultry products and non-poultry-related contact such as from H5N1
      contaminated water. While most H5N1 cases are attributed to exposure to sick
      poultry, it is unclear how many may be due to human-to-human transmission. The
      collective results of published literature suggest that transmission risk of H5N1
      from poultry to humans may be highest among individuals who may have been in
      contact with the highest potential concentrations of virus shed by poultry. This
      suggests that there may be a threshold of virus concentration needed for
      effective transmission and that circulating H5N1 strains have not yet mutated to
      transmit readily from either poultry to human or from human to human. However,
      the mode of potential transmission can be quite varied throughout different
      countries and by study with exposures ranging from visiting a wet market,
      preparing infected poultry for consumption, to swimming or bathing in ponds
      frequented by poultry. Several important data gaps remain in the understanding of
      the epidemiology of H5N1 in humans and limit our ability to interpret the results
      of the available H5N1 seroepidemiologic studies. 

PMID- 24034479
TI  - Intervention strategies to reduce the risk of zoonotic infection with avian
      influenza viruses: scientific basis, challenges and knowledge gaps.
AB  - A range of measures has been recommended and used for the control and prevention
      of avian influenza. These measures are based on the assessment of local
      epidemiological situations, field observations and other scientific information.
      Other non-technical factors are (or in some cases should be) taken into account
      when developing and recommending control measures. The precise effects under
      field conditions of most individual interventions applied to control and prevent
      avian influenza have not been established or subjected to critical review, often
      because a number of measures are applied simultaneously without controls. In most
      cases, the combination of measures used results in control or elimination of the
      virus although there are some countries where this has not been the case. In
      others, especially those with low poultry density, it is not clear whether the
      link between the adoption of a set of measures and the subsequent control of the
      disease is causative. This article discusses the various measures recommended,
      with particular emphasis on stamping out and vaccination, examines how these
      measures assist in preventing zoonotic infections with avian influenza viruses
      and explores gaps in knowledge regarding their effectiveness. 

PMID- 24034481
TI  - Animal influenza research needs: protecting humans, animals, food, and economies.

PMID- 24034478
TI  - Virus-specific factors associated with zoonotic and pandemic potential.
AB  - Influenza A is a highly contagious respiratory virus in constant evolution and
      represents a threat to both veterinary and human public health. IA viruses (IAVs)
      originate in avian reservoirs but may adapt to humans, either directly or through
      the spillover to another mammalian species, to the point of becoming pandemic.
      IAVs must successfully be able to (i) transmit from animal to human, (ii)
      interact with host cells, and (iii) transmit from human to human. The mechanisms
      by which viruses evolve, cause zoonotic infections, and adapt to a new host
      species are indeed complex and appear to be a heterogeneous collection of viral
      evolutionary events rather than a single phenomenon. Progress has been made in
      identifying some of the genetic markers mainly associated with virulence and
      transmission; this achievement has improved our knowledge of how to manage a
      pandemic event and of how to identify IAVs with pandemic potential. Early
      evidence of emerging viruses and surveillance of animal IAVs is made possible
      only by strengthening the collaboration between the public and veterinary health
      sectors. 

PMID- 24034482
TI  - An updated systematic review of the role of host genetics in susceptibility to
      influenza.
AB  - The World Health Organization has identified studies of the role of host genetics
      on susceptibility to severe influenza as a priority. A systematic review was
      conducted in June 2011 to summarise the evidence on the role of host genetics in
      susceptibility to influenza, and this report updates that previously published
      review. Animal studies suggest that genetic control of susceptibility to severe
      influenza in mice is complex and not controlled by a single locus, but there is
      encouraging evidence that some of the host genetic determinants of susceptibility
      to severe disease may be common across influenza subtypes. Although a number of
      studies on genetic susceptibility to influenza in humans have been published
      recently, all are underpowered and unreplicated, so do not provide robust
      statistical evidence of an association between the identified genetic loci and
      susceptibility. One study does however present convincing functional evidence for
      an important role for IFITM3 in susceptibility to severe influenza in mice, and
      some evidence that this may also be important in human A/H1N1/pdm2009 infection. 

PMID- 24034484
TI  - Improving influenza vaccine virus selection: report of a WHO informal
      consultation held at WHO headquarters, Geneva, Switzerland, 14-16 June 2010.

PMID- 24034483
TI  - Routes of influenza transmission.
AB  - Remarkably little is known definitively about the modes of influenza
      transmission. Thus, important health policy and infection control issues remain
      unresolved. These shortcomings have been exposed in national and international
      pandemic preparedness activities over recent years. Indeed, WHO, CDC, ECDC and
      the U.S. Institute of Medicine have prioritised understanding the modes of
      influenza transmission as a critical need for pandemic planning. Studying
      influenza transmission is difficult; seasonality, unpredictable attack rates,
      role of environmental parameters such as temperature and humidity, numbers of
      participants required and confounding variables all present considerable
      obstacles to the execution of definitive studies. A range of investigations
      performed to date have failed to provide definitive answers and key questions
      remain. Reasons for this include the fact that many studies have not sought to
      investigate routes of transmission as a primary objective (instead, they have
      evaluated specific interventions) and that fieldwork in natural settings,
      specifically assessing the dynamics and determinants of transmission between
      humans, has been limited. The available evidence suggests that all routes of
      transmission (droplet, aerosol and contact) have a role to play; their relative
      significance will depend on the set of circumstances acting at a given time.
      Dictating the process are factors related to the virus itself, the host and the
      environment. 

PMID- 24034485
TI  - Impact of H1N1 on socially disadvantaged populations: summary of a systematic
      review.
AB  - BACKGROUND: Previous reviews found that the H1N1 pandemic was associated with a
      large proportion of hospitalizations, severe illness, workplace absenteeism, and
      high costs. However, the burden among socially disadvantaged groups of the
      population is unclear. This is a summary of a previously published systematic
      review commissioned by the World Health Organization on the burden of H1N1
      pandemic (influenza A/Mexico/2009 (H1N1)) among socially disadvantaged
      populations. METHODS: MEDLINE and EMBASE were searched to identify studies
      reporting hospitalization, severe illness, and mortality attributable to the 2009
      H1N1 pandemic among socially disadvantaged populations, including ethnic
      minorities and low-income or lower-middle-income economy countries (LIC/LMIC).
      SAS and Review Manager were used to conduct random effects meta-analysis.
      RESULTS: Forty-eight cohort studies and 14 companion reports including 44 777
      patients were included after screening 787 citations and 164 full-text articles.
      Twelve of the included studies provided data on LIC/LMIC, including one study
      from Guatemala, two from Morocco, one from Pakistan, and eight from India, plus
      four companion reports. The rest provided data on ethnic minorities living in
      high-income economy countries (HIC). Significantly more hospitalizations were
      observed among ethnic minorities versus nonethnic minorities in two North
      American studies [1313 patients, odds ratio (OR) 2.26 (95% confidence interval:
      1.53-3.32)]. Among hospitalized patients in HIC, statistically significant
      differences in intensive care unit admissions (n = 8 studies, 15 352 patients, OR
      0.84 [0.69-1.02]) and deaths (n = 6 studies, 14 757 patients, OR 0.85 [95% CI:
      0.73-1.01]) were not observed. CONCLUSION: We found significantly more
      hospitalizations among ethnic minorities versus nonethnic minorities in North
      America, yet no differences in intensive care unit admissions or deaths among
      H1N1-infected hospitalized patients were observed in North America and Australia.
      Our results suggest a similar burden of H1N1 between ethnic minorities and
      nonethnic minorities living in HIC.

PMID- 24034486
TI  - Assessing key model parameters for economic evaluation of pandemic influenza
      interventions: the data source matters.
AB  - BACKGROUND: In our previous systematic review of economic evaluations of pandemic
      influenza interventions, five model parameters, namely probability of pandemic,
      duration of pandemic, severity, attack rate, and intervention efficacy, were not
      only consistently used in all studies but also considered important by authors.
      OBJECTIVES: Because these parameters originated from sources of varying quality
      ranging from experimental studies to expert opinion, this study aims to analyze
      the variation in values used according to sources of information across studies.
      METHODS: An analysis of estimated values of key parameters for economic modeling
      was performed against their different data sources, following the standard
      hierarchy of evidence. RESULTS: A lack of good-quality evidence to estimate
      pandemic duration, pandemic probability, and mortality reduction from antiviral
      treatment results in a large variation of values used in economic evaluations.
      Although there are variations in quality of evidence used for attack rate, basic
      reproduction number, and reduction in hospitalizations from antiviral treatment,
      the estimated values do not vary significantly. The use of higher-quality
      evidence results in better precision of estimated values compared to lower
      quality sources. CONCLUSION: Hierarchies of evidence are a necessary tool to
      identify appropriate model parameters to populate economic evaluations and should
      be included in methodological guidelines. Knowledge gaps in some key parameters
      should be addressed, because if good-quality evidence is available, future
      economic evaluations will be more reliable. Some gaps may not be fulfilled by
      research but consensus among experts to ensure consistency in the use of these
      assumptions.

PMID- 24034487
TI  - Macroeconomic impact of pandemic influenza and associated policies in Thailand,
      South Africa and Uganda.
AB  - BACKGROUND: Research has shown the value of conducting a macroeconomic analysis
      of the impact of influenza pandemics. However, previous modelling applications
      focus on high-income countries, and there is a lack of evidence concerning the
      potential impact of an influenza pandemic on lower- and middle-income countries.
      OBJECTIVES: To estimate the macroeconomic impact of pandemic influenza in
      Thailand, South Africa and Uganda with particular reference to pandemic (H1N1)
      2009. METHODS: A single-country whole-economy Computable General Equilibrium
      (CGE) model was set up for each of the three countries in question and used to
      estimate the economic impact of declines in labour attributable to morbidity,
      mortality and school closure. RESULTS: Overall GDP impacts were less than 1% of
      GDP for all countries and scenarios. Uganda's losses were proportionally larger
      than those of Thailand and South Africa. Labour-intensive sectors suffer the
      largest losses. CONCLUSION: The economic cost of unavoidable absence in the event
      of an influenza pandemic could be proportionally larger for low-income countries.
      The cost of mild pandemics, such as pandemic (H1N1) 2009, appears to be small,
      but could increase for more severe pandemics and/or pandemics with greater
      behavioural change and avoidable absence.

PMID- 24034488
TI  - Influenza vaccination for immunocompromised patients: summary of a systematic
      review and meta-analysis.
AB  - Vaccination of immunocompromised patients is recommended in many national
      guidelines to protect against severe or complicated influenza infection. However,
      due to uncertainties over the evidence base, implementation is frequently patchy
      and dependent on individual clinical discretion. We conducted a systematic review
      and meta-analysis to assess the evidence for influenza vaccination in this
      patient group. Healthcare databases and grey literature were searched and
      screened for eligibility. Data extraction and assessments of risk of bias were
      undertaken in duplicate, and results were synthesised narratively and using meta
      analysis where possible. Our data show that whilst the serological response
      following vaccination of immunocompromised patients is less vigorous than in
      healthy controls, clinical protection is still meaningful, with only mild
      variation in adverse events between aetiological groups. Although we encountered
      significant clinical and statistical heterogeneity in many of our meta-analyses,
      we advocate that immunocompromised patients should be targeted for influenza
      vaccination. 

PMID- 24034489
TI  - Antivirals for influenza: a summary of a systematic review and meta-analysis of
      observational studies.
AB  - Despite the use of antivirals to treat patients with severe influenza, questions
      remain with respect to effects and safety. Although a recent systematic review
      has provided some indication of benefit, the analysis is limited by the quality
      of the available evidence from randomized controlled trials. To supplement the
      existing information, the authors conducted a systematic review of observational
      studies of antiviral treatment for influenza. This report summarises the findings
      of that review. Similar to the randomised trials, the confidence in the estimates
      of the effects for decision-making is low to very low primarily due to the risk
      of selection and publication bias in the observational studies. From these
      observational studies, the summary estimates suggest that oseltamivir may reduce
      mortality, hospitalisation and duration of symptoms compared with no treatment.
      Inhaled zanamivir may also reduce symptom duration and hospitalisations, but
      patients may experience more complications compared with no treatment. Earlier
      treatment with antivirals is generally associated with better outcomes than later
      treatment. Further high-quality evidence is needed to inform treatment guidelines
      because of the overall low to very low quality of evidence. 

PMID- 24034490
TI  - Supply of neuraminidase inhibitors related to reduced influenza A (H1N1)
      mortality during the 2009-2010 H1N1 pandemic: summary of an ecological study.
AB  - When the influenza A (H1N1) pandemic spread across the globe from April 2009 to
      August 2010, many WHO Member States used antiviral drugs, specifically
      neuraminidase inhibitors (NAIs) oseltamivir and zanamivir, to treat influenza
      patients in critical condition. Antivirals have been found to be effective in
      reducing severity and duration of influenza illness, and likely reduce morbidity;
      however, it is unclear whether NAIs used during the pandemic reduced H1N1
      mortality. To assess the association between antivirals and influenza mortality,
      at an ecologic level, country-level data on supply of oseltamivir and zanamivir
      were compared to laboratory-confirmed H1N1 deaths (per 100 000 people) from July
      2009 to August 2010 in 42 WHO Member States. From this analysis, it was found
      that each 10% increase in kilograms of oseltamivir, per 100 000 people, was
      associated with a 1.6% reduction in H1N1 mortality over the pandemic period
      [relative rate (RR) = 0.84 per log increase in oseltamivir supply]. Each 10%
      increase in kilogram of active zanamivir, per 100 000, was associated with a 0.3%
      reduction in H1N1 mortality (RR = 0.97 per log increase). While limitations exist
      in the inference that can be drawn from an ecologic evaluation, this analysis
      offers evidence of a protective relationship between antiviral drug supply and
      influenza mortality and supports a role for influenza antiviral use in future
      pandemics. This article summarises the original study described previously, which
      can be accessed through the following citation: Miller PE, Rambachan A, Hubbard
      RJ, Li J, Meyer AE, et al. (2012) Supply of Neuraminidase Inhibitors Related to
      Reduced Influenza A (H1N1) Mortality during the 2009-2010 H1N1 Pandemic: An
      Ecological Study. PLoS ONE 7(9): e43491. 

PMID- 24034491
TI  - Clinical care for severe influenza and other severe illness in resource-limited
      settings: the need for evidence and guidelines.
AB  - The 2009 influenza A (H1N1) pandemic highlighted the importance of quality
      hospital care of the severely ill, yet there is evidence that the impact of the
      2009 pandemic was highest in low- and middle-income countries with fewer
      resources. Recent data indicate that death and suffering from seasonal influenza
      and severe illness in general are increased in resource-limited settings.
      However, there are limited clinical data and guidelines for the management of
      influenza and other severe illness in these settings. Life-saving supportive care
      through syndromic case management is used successfully in high-resource intensive
      care units and in global programs such as the Integrated Management of Childhood
      Illness (IMCI). While there are a variety of challenges to the management of the
      severely ill in resource-limited settings, several new international initiatives
      have begun to develop syndromic management strategies for these environments,
      including the World Health Organization's Integrated Management of Adult and
      Adolescent Illness Program. These standardized clinical guidelines emphasize
      syndromic case management and do not require high-resource intensive care units.
      These efforts must be enhanced by quality clinical research to provide missing
      evidence and to refine recommendations, which must be carefully integrated into
      existing healthcare systems. Realizing a sustainable, global impact on death and
      suffering due to severe influenza and other severe illness necessitates an
      ongoing and concerted international effort to iteratively generate, implement,
      and evaluate best-practice management guidelines for use in resource-limited
      settings. 

PMID- 24034492
TI  - Vaccination of healthcare workers to protect patients at increased risk of acute
      respiratory disease: summary of a systematic review.
AB  - Healthcare workers (HCWs) are at increased risk of exposure to respiratory
      pathogens and may transmit infection to vulnerable patients. This study
      summarises a recent systematic review, which aimed to assess evidence that
      influenza or pneumococcal vaccination of HCWs provides indirect protection for
      those patients most at risk of severe or complicated acute respiratory infection.
      A number of healthcare databases and sources of grey literature were searched
      using a predefined strategy, and citations screened for eligibility in accordance
      with specified inclusion criteria. Risk of bias was assessed using validated
      tools and results summarised qualitatively. Twenty papers were included in the
      final review, all of which considered influenza vaccination of HCW. As such,
      planned subanalysis of pneumococcal vaccination was discarded. The majority of
      primary research studies included (11/14) were conducted in long-term care
      facilities, but there was marked heterogeneity in terms of the population,
      intervention/exposure and outcomes considered. Consistency in the direction of
      effect was observed across several different outcome measures, suggesting that
      influenza vaccination of HCWs is likely to offer some protection. Further
      evidence is, however, required from acute care settings. 

PMID- 24034493
TI  - Healthcare worker compliance with seasonal and pandemic influenza vaccination.
AB  - Healthcare workers (HCWs) can be an important source of transmission of influenza
      to patients and family members, and their well-being is fundamental to the
      maintenance of healthcare services during influenza outbreaks and pandemics.
      Unfortunately, studies have shown consistently low levels of compliance with
      influenza vaccination among HCWs, a finding that became particularly pronounced
      during recent pandemic vaccination campaigns. Among the variables associated with
      vaccine acceptance in this group are demographic factors, fears and concerns over
      vaccine safety and efficacy, perceptions of risk and personal vulnerability, past
      vaccination behaviours and experience with influenza illness, as well as certain
      situational and organisational constructs. We report the findings of a review of
      the literature on these factors and highlight some important challenges in
      interpreting the data. In particular, we point out the need for longitudinal
      study designs, as well as focused research and interventions that are adapted to
      the most resistant HCW groups. Multi-pronged strategies are an important step
      forward in ensuring that future influenza vaccination campaigns, whether directed
      at seasonal or pandemic strains, will be successful in ensuring broad coverage
      among HCWs. 

PMID- 24034494
TI  - Bacterial and viral infections associated with influenza.
AB  - Influenza-associated bacterial and viral infections are responsible for high
      levels of morbidity and death during pandemic and seasonal influenza episodes. A
      review was undertaken to assess and evaluate the incidence, epidemiology,
      aetiology, clinical importance and impact of bacterial and viral co-infection and
      secondary infection associated with influenza. A review was carried out of
      published articles covering bacterial and viral infections associated with
      pandemic and seasonal influenza between 1918 and 2009 (and published through
      December 2011) to include both pulmonary and extra-pulmonary infections. While
      pneumococcal infection remains the predominant cause of bacterial pneumonia, the
      review highlights the importance of other co- and secondary bacterial and viral
      infections associated with influenza, and the emergence of newly identified dual
      infections associated with the 2009 H1N1 pandemic strain. Severe influenza
      associated pneumonia is often bacterial and will necessitate antibiotic
      treatment. In addition to the well-known bacterial causes, less common bacteria
      such as Legionella pneumophila may also be associated with influenza when new
      influenza strains emerge. This review should provide clinicians with an overview
      of the range of bacterial and viral co- or secondary infections that could
      present with influenza illness. 

PMID- 24034495
TI  - Unresolved issues in risk communication research: the case of the H1N1 pandemic
      (2009-2011).
AB  - The 2009 H1N1 pandemic had considerable impact on risk perceptions, vaccination
      campaigns, and global health governance. In this context, risk communication
      issues have been probably the most puzzling and the least understood in
      retrospect. This article reviews the current knowledge on the following issues:
      risk and pandemic perceptions; vaccination perceptions and practices; rumors and
      rumor propagation; and health risk communication. It also highlights the research
      gaps in these areas that remain to be further explored in the future. 

PMID- 24034497
TI  - Poly(ethylene glycol)-block-cationic polylactide nanocomplexes of differing
      charge density for gene delivery.
AB  - Representing a new type of biodegradable cationic block copolymer, well-defined
      poly(ethylene glycol)-block-cationic polylactides (PEG-b-CPLAs) with tertiary
      amine-based cationic groups were synthesized by thiol-ene functionalization of an
      allyl-functionalized diblock precursor. Subsequently the application of PEG-b
      CPLAs as biodegradable vectors for the delivery of plasmid DNAs (pDNAs) was
      investigated. Via the formation of PEG-b-CPLA:pDNA nanocomplexes by spontaneous
      electrostatic interaction, pDNAs encoding luciferase or enhanced green
      fluorescent protein were successfully delivered to four physiologically distinct
      cell lines (including macrophage, fibroblast, epithelial, and stem cell).
      Formulated nanocomplexes demonstrated high levels of transfection with low levels
      of cytotoxicity and hemolysis when compared to a positive control. Biophysical
      characterization of charge densities of nanocomplexes at various polymer:pDNA
      weight ratios revealed a positive correlation between surface charge and gene
      delivery. Nanocomplexes with high surface charge densities were utilized in an in
      vitro serum gene delivery inhibition assay, and effective gene delivery was
      observed despite high levels of serum. Overall, these results help to elucidate
      the influence of charge, size, and PEGylation of nanocomplexes upon the delivery
      of nucleic acids in physiologically relevant conditions.

PMID- 24034498
TI  - PEGylated fullerene/iron oxide nanocomposites for photodynamic therapy, targeted
      drug delivery and MR imaging.
AB  - Recently, fullerene and fullerene derivatives owning to their highly enriched
      physical and chemical properties have been widely explored for applications in
      many different fields including biomedicine. In this study, iron oxide
      nanoparticles (IONPs) were decorated onto the surface of fullerene (C60), and
      then PEGylation was performed to improve the solubility and biocompatibility of
      C60-IONP, obtaining a multi-functional C60-IONP-PEG nanocomposite with strong
      superparamagnetism and powerful photodynamic therapy capacity. Hematoporphyrin
      monomethyl ether (HMME), a new photodynamic anti-cancer drug, was conjugated to
      C60-IONP-PEG, forming a C60-IONP-PEG/HMME drug delivery system, which
      demonstrated an excellent magnetic targeting ability in cancer therapy. Compared
      with free HMME, remarkably enhanced photodynamic cancer cell killing effect using
      C60-IONP-PEG/HMME was realized not only in a cultured B16-F10 cells in vitro but
      also in an in vivo murine tumor model due to 23-fold higher HMME uptake of tumor
      and strong photodynamic activity of C60-IONP-PEG. Moreover, C60-IONP-PEG could be
      further used as a T2-contrast agent for in vivo magnetic resonance imaging. Our
      work showed C60-IONP-PEG/HMME had a great potential for cancer theranostic
      applications.

PMID- 24034496
TI  - Characterization of synergistic anti-cancer effects of docosahexaenoic acid and
      curcumin on DMBA-induced mammary tumorigenesis in mice.
AB  - BACKGROUND: The major obstacles to the successful use of individual nutritional
      compounds as preventive or therapeutic agents are their efficacy and
      bioavailability. One approach to overcoming this problem is to use combinations
      of nutrients to induce synergistic effects. The objective of this research was to
      investigate the synergistic effects of two dietary components: docosahexaenoic
      acid (DHA), an omega-3 fatty acid present in cold-water fish, and curcumin (CCM),
      an herbal nutrient present in turmeric, in an in vivo model of DMBA-induced
      mammary tumorigenesis in mice. METHODS: We used the carcinogen DMBA to induce
      breast tumors in SENCAR mice on control, CCM, DHA, or DHA + CCM diets. Appearance
      and tumor progression were monitored daily. The tumors were harvested 15 days
      following their first appearance for morphological and immunohistological
      analysis. Western analysis was performed to determine expression of maspin and
      survivin in the tumor tissues. Characterization of tumor growth was analyzed
      using appropriate statistical methods. Otherwise all other results are reported
      as mean +/- SD and analyzed with one-way ANOVA and Tukey's post hoc procedure.
      RESULTS: Analysis of gene microarray data indicates that combined treatment with
      DHA + CCM altered the profile of "PAM50" genes in the SK-BR-3 cell line from an
      ER-/Her-2+ to that resembling a "normal-like" phenotype. The in vivo studies
      demonstrated that DHA + CCM treatment reduced the incidence of breast tumors,
      delayed tumor initiation, and reduced progression of tumor growth. Dietary
      treatment had no effect on breast size development, but tumors from mice on a
      control diet (untreated) were less differentiated than tumors from mice fed CCM
      or DHA + CCM diets. The synergistic effects also led to increased expression of
      the pro-apoptotic protein, maspin, but reduced expression of the anti-apoptotic
      protein, survivin. CONCLUSIONS: The SK-BR-3 cells and DMBA-induced tumors, both
      with an ER- and Her-2+ phenotype, were affected by the synergistic interaction of
      DHA and CCM. This suggests that the specific breast cancer phenotype is an
      important factor for predicting efficacy of these nutraceuticals. The combination
      of DHA and CCM is potentially a dietary supplemental treatment for some breast
      cancers, likely dependent upon the molecular phenotype of the cancer.

PMID- 24034499
TI  - In vivo ultrasound visualization of non-occlusive blood clots with thrombin
      sensitive contrast agents.
AB  - The use of microbubbles as ultrasound contrast agents is one of the primary
      methods to diagnose deep venous thrombosis. However, current microbubble imaging
      strategies require either a clot sufficiently large to produce a circulation
      filling defect or a clot with sufficient vascularization to allow for targeted
      accumulation of contrast agents. Previously, we reported the design of a
      microbubble formulation that modulated its ability to generate ultrasound
      contrast from interaction with thrombin through incorporation of aptamer
      containing DNA crosslinks in the encapsulating shell, enabling the measurement of
      a local chemical environment by changes in acoustic activity. However, this
      contrast agent lacked sufficient stability and lifetime in blood to be used as a
      diagnostic tool. Here we describe a PEG-stabilized, thrombin-activated
      microbubble (PSTA-MB) with sufficient stability to be used in vivo in circulation
      with no change in biomarker sensitivity. In the presence of actively clotting
      blood, PSTA-MBs showed a 5-fold increase in acoustic activity. Specificity for
      the presence of thrombin and stability under constant shear flow were
      demonstrated in a home-built in vitro model. Finally, PSTA-MBs were able to
      detect the presence of an active clot within the vena cava of a rabbit
      sufficiently small as to not be visible by current non-specific contrast agents.
      By activating in non-occlusive environments, these contrast agents will be able
      to detect clots not diagnosable by current contrast agents.

PMID- 24034501
TI  - Vertical electric field stimulated neural cell functionality on porous amorphous
      carbon electrodes.
AB  - We demonstrate the efficacy of amorphous macroporous carbon substrates as
      electrodes to support neuronal cell proliferation and differentiation in electric
      field mediated culture conditions. The electric field was applied perpendicular
      to carbon substrate electrode, while growing mouse neuroblastoma (N2a) cells in
      vitro. The placement of the second electrode outside of the cell culture medium
      allows the investigation of cell response to electric field without the
      concurrent complexities of submerged electrodes such as potentially toxic
      electrode reactions, electro-kinetic flows and charge transfer (electrical
      current) in the cell medium. The macroporous carbon electrodes are uniquely
      characterized by a higher specific charge storage capacity (0.2 mC/cm(2)) and low
      impedance (3.3 kOmega at 1 kHz). The optimal window of electric field stimulation
      for better cell viability and neurite outgrowth is established. When a uniform or
      a gradient electric field was applied perpendicular to the amorphous carbon
      substrate, it was found that the N2a cell viability and neurite length were
      higher at low electric field strengths (<= 2.5 V/cm) compared to that measured
      without an applied field (0 V/cm). While the cell viability was assessed by two
      complementary biochemical assays (MTT and LDH), the differentiation was studied
      by indirect immunostaining. Overall, the results of the present study
      unambiguously establish the uniform/gradient vertical electric field based
      culture protocol to either enhance or to restrict neurite outgrowth respectively
      at lower or higher field strengths, when neuroblastoma cells are cultured on
      porous glassy carbon electrodes having a desired combination of electrochemical
      properties.

PMID- 24034500
TI  - Aqueous two-phase printing of cell-containing contractile collagen microgels.
AB  - This work describes the use of aqueous two-phase systems to print cell-containing
      contractile collagen microdroplets. The fully aqueous conditions enable
      convenient formation of sub-microliter 'microgels' that are much smaller than
      otherwise possible to fabricate while maintaining high cell viability. The
      produced microgels contract over several days, mimicking the behavior of
      macroscale contraction assays, which have been valued as an important biological
      readout for over three decades. Use of microgels not only reduces reagent
      consumption and increases throughput of the assay, but also improves transport of
      molecules into and out of the collagen matrix, thereby enabling efficient and
      more precise studies of timed stimulation profiles. Utility of the technology is
      demonstrated by analyzing the effects of TGF-beta1 on gel contraction, and we
      demonstrate that brief 'burst' stimulation profiles in microgels prompt
      contraction of the matrix, a feature not observed in the conventional macroscale
      assay. The fully aqueous process also enables the integration of contractile
      collagen microgels within existing cell culture systems, and we demonstrate proof
      of-principle experiments in which a contractile collagen droplet is fabricated in
      situ on an existing epithelial monolayer. The simplicity, versatility and ability
      to robustly produce collagen microgels should allow effective translation of this
      microengineering technology into a variety of research environments.

PMID- 24034502
TI  - A review of optical imaging and therapy using nanosized graphene and graphene
      oxide.
AB  - Nanosized graphene and graphene oxide (GO) are photoluminescent due to the
      presence of bandgaps and edges/defects. The excellent photostability of these
      nanomaterials makes them superior to molecular dyes for biological imaging. They
      can also produce intensive heat under laser irradiation, enabling them to serve
      as photothermal agents for cancer treatment. In this work, recent studies on the
      photoluminescence of these materials, their applications for biological imaging
      and photothermal cancer therapy are reviewed. Properties of laser, particularly
      the temporal property (continuous wave or pulsed), affect its interaction with
      materials. Therefore, the photoluminescence and photothermal effects, as well as
      their applications under both single (one)-photon (continuous wave laser) and two
      photon (pulsed laser) excitation were summarized and analyzed. Synergistic
      therapy which combines chemotherapy and photothermal therapy using these
      materials is also reviewed. Finally, critical issues and challenges for further
      research and in medical applications of these materials are analyzed.

PMID- 24034503
TI  - Polybutylcyanoacrylate nanoparticles for delivering hormone response element
      conjugated neurotrophin-3 to the brain of intracerebral hemorrhagic rats.
AB  - Hypertensive intracerebral hemorrhage (ICH) is a rapidly evolutional pathology,
      inducing necrotic cell death followed by apoptosis, and alters gene expression
      levels in surrounding tissue of an injured brain. For ICH therapy by controlled
      gene release, the development of intravenously administrable delivery vectors to
      promote the penetration across the blood-brain barrier (BBB) is a critical
      challenge. To enhance transfer efficiency of genetic materials under hypoxic
      conditions, polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were used to
      mediate the intracellular transport of plasmid neurotrophin-3 (NT-3) containing
      hormone response element (HRE) with a cytomegalovirus (cmv) promoter and to
      differentiate induced pluripotent stem cells (iPSCs). The differentiation ability
      of iPSCs to neurons was justified by various immunological stains for protein
      fluorescence. The effect of PBCA NP/cmvNT-3-HRE complexes on treating ICH rats
      was studied by immunostaining, western blotting and Nissl staining. We found that
      the treatments with PBCA NP/cmvNT-3-HRE complexes increased the capability of
      differentiating iPSCs to express NT-3, TrkC and MAP-2. Moreover, PBCA NPs could
      protect cmvNT-3-HRE against degradation with EcoRI/PstI and DNase I in vitro and
      raise the delivery across the BBB in vivo. The administration of PBCA NP/cmvNT-3
      HRE complexes increased the expression of NT-3, inhibited the expression of
      apoptosis-inducing factor, cleaved caspase-3 and DNA fragmentation, and reduced
      the cell death rate after ICH in vivo. PBCA NPs are demonstrated as an
      appropriate delivery system for carrying cmvNT-3-HRE to the brain for ICH
      therapy.

PMID- 24034504
TI  - The effect of elastomer chain flexibility on protein adsorption.
AB  - Cells are known to respond differently when grown on materials of varying
      stiffness. However, the mechanism by which a cell senses substrate stiffness is
      unknown. Lower crosslink density elastomers formed from acrylated star-poly(d,l
      lactide-co-epsilon-caprolactone) have previously been shown to support higher
      smooth muscle cell proliferation in in vitro culture. This difference in growth
      was hypothesized to be due to differences in protein adsorption that resulted
      from differences in polymer chain mobility at the surface. Therefore, layer mass
      and viscoelastic properties were measured for HSA, IgG, fibronectin, vitronectin,
      and serum supplemented media adsorbed to elastomers of two crosslink densities.
      Significantly more fibronectin adsorbed to the lower crosslink density surface
      while significantly more IgG adsorbed to the higher crosslink density surface.
      Furthermore, differences in fibronectin and IgG layer shear moduli were observed,
      suggesting that there was a difference in the conformation of the adsorbed
      protein. ATR-FTIR analysis showed that the lower crosslink density elastomer
      absorbed more surface water. The increased amount of water may cause greater
      entropic gains upon protein adsorption to the lower crosslink density surface,
      which increases total protein adsorption from serum and may cause differences in
      protein conformation and thus cell behavior.

PMID- 24034505
TI  - Critical factors in the translation of improved antimicrobial strategies for
      medical implants and devices.
AB  - Biomaterials-associated infection incidence represents an increasing clinical
      challenge as more people gain access to medical device technologies worldwide and
      microbial resistance to current approaches mounts. Few reported antimicrobial
      approaches to implanted biomaterials ever get commercialized for physician use
      and patient benefit. This is not for lack of ideas since many thousands of claims
      to new approaches to antimicrobial efficacy are reported. Lack of translation of
      reported ideas into medical products approved for use, results from conflicting
      goals and purposes between the various participants involved in conception,
      validation, development, commercialization, safety and regulatory oversight,
      insurance reimbursement, and legal aspects of medical device innovation. The
      scientific causes, problems and impressive costs of the limiting clinical options
      for combating biomaterials-associated infection are well recognized. Demands for
      improved antimicrobial technologies constantly appear. Yet, the actual human,
      ethical and social costs and consequences of their occurrence are less
      articulated. Here, we describe several clinical cases of biomaterials-associated
      infections to illustrate the often-missing human elements of these infections. We
      identify the current societal forces at play in translating antimicrobial
      research concepts into clinical implant use and their often-orthogonal
      constituencies, missions and policies. We assert that in the current complex
      environment between researchers, funding agencies, physicians, patients,
      providers, producers, payers, regulatory agencies and litigators, opportunities
      for translatable successes are minimized under the various risks assumed in the
      translation process. This argues for an alternative approach to more effectively
      introduce new biomaterials and device technologies that can address the clinical
      issues by providing patients and medical practitioners new options for desperate
      clinical conditions ineffectively addressed by biomedical innovation. 

PMID- 24034506
TI  - The effects of pregnancy intention on the use of antenatal care services:
      systematic review and meta-analysis.
AB  - BACKGROUND: There has been considerable debate in the reproductive health
      literature as to whether unintended pregnancy influences use of maternal health
      services, particularly antenatal care. Despite the wealth of studies examining
      the association between pregnancy intention and antenatal care, findings remain
      mixed and inconclusive. The objective of this study is to systematically review
      and meta-analyse studies on the association between pregnancy intention and
      antenatal care. METHODS: We reviewed studies reporting on pregnancy intention and
      antenatal care from PubMed, Popline, CINHAL and Jstor search engines by
      developing search strategies. Study quality was assessed for biases in selection,
      definition of exposure and outcome variables, confounder adjustment, and type of
      analyses. Adjusted odds ratios, standard errors and sample size were extracted
      from the included studies and meta-analyzed using STATA version 11. Heterogeneity
      among studies was assessed using Q test statistic. Effect-size was measured by
      Odds ratio. Pooled odds ratio for the effects of unintended pregnancy on the use
      of antenatal care services were calculated using the random effects model.
      RESULTS: Our results indicate increased odds of delayed antenatal care use among
      women with unintended pregnancies (OR 1.42 with 95% CI, 1.27, 1.59) as compared
      to women with intended pregnancies. Sub-group analysis for developed (1.50 with
      95% CI, 1.34, 1.68) and developing (1. 36 with 95% CI, 1.13, 1.65) countries
      showed significant associations. Moreover, there is an increased odds of
      inadequate antenatal care use among women with unintended pregnancies as compared
      to women with intended pregnancies (OR 1.64, 95% CI: 1.47, 1.82). Subgroup
      analysis for developed (OR, 1.86; 95% CI: 1.62, 2.14) and developing (OR, 1.54;
      95% CI: 1.33, 1.77) countries also showed a statistically significant
      association. However, there were heterogeneities in the studies included in this
      analysis. CONCLUSION: Unintended pregnancy is associated with late initiation and
      inadequate use of antenatal care services. Hence, women who report an unintended
      pregnancy should be targeted for antenatal care counseling and services to
      prevent adverse maternal and perinatal outcomes. Moreover, providing information
      on the importance of planning and healthy timing of pregnancies, and the means to
      do so, to all women of reproductive ages is essential.

PMID- 24034507
TI  - An EM algorithm based on an internal list for estimating haplotype distributions
      of rare variants from pooled genotype data.
AB  - BACKGROUND: Pooling is a cost effective way to collect data for genetic
      association studies, particularly for rare genetic variants. It is of interest to
      estimate the haplotype frequencies, which contain more information than single
      locus statistics. By viewing the pooled genotype data as incomplete data, the
      expectation-maximization (EM) algorithm is the natural algorithm to use, but it
      is computationally intensive. A recent proposal to reduce the computational
      burden is to make use of database information to form a list of frequently
      occurring haplotypes, and to restrict the haplotypes to come from this list only
      in implementing the EM algorithm. There is, however, the danger of using an
      incorrect list, and there may not be enough database information to form a list
      externally in some applications. RESULTS: We investigate the possibility of
      creating an internal list from the data at hand. One way to form such a list is
      to collapse the observed total minor allele frequencies to "zero" or "at least
      one", which is shown to have the desirable effect of amplifying the haplotype
      frequencies. To improve coverage, we propose ways to add and remove haplotypes
      from the list, and a benchmarking method to determine the frequency threshold for
      removing haplotypes. Simulation results show that the EM estimates based on a
      suitably augmented and trimmed collapsed data list (ATCDL) perform
      satisfactorily. In two scenarios involving 25 and 32 loci respectively, the EM
      ATCDL estimates outperform the EM estimates based on other lists as well as the
      collapsed data maximum likelihood estimates. CONCLUSIONS: The proposed augmented
      and trimmed CD list is a useful list for the EM algorithm to base upon in
      estimating the haplotype distributions of rare variants. It can handle more
      markers and larger pool size than existing methods, and the resulting EM-ATCDL
      estimates are more efficient than the EM estimates based on other lists.

PMID- 24034508
TI  - The short and "shorter" of it: >1750 tapered titanium stems at 6- to 88-month
      follow-up.
AB  - INTRODUCTION: Femoral fixation in THA can be achieved with different design
      rationales. Our hypothesis was that two short titanium flat-tapered stems would
      demonstrate similar stability. METHODS: Between May 2005 and May 2012, 849 short
      (135-170mm), titanium flat stems ("Short") were used in THA. Between July 2005
      and May 2012, 902 similar, but 35-mm shorter, stems ("Shorter") were utilized.
      Harris Hip Score, radiographic, and survivorship data were analyzed. RESULTS:
      Survivorship of the "Short" stems was 99.1% at 7years. Eight of 849 stems have
      been revised: 4 for loosening, 3 for fracture, and 1 for infection. Harris Hip
      Score improved from 41.6 to 88.9. In the "Shorter" group, 9 of 902 have been
      revised: 6 for fracture/loosening, 2 for infection, and 1 for instability. HHs
      improved from 43.7 to 92.0. No statistically significant differences were noted
      in revision rate. CONCLUSION: This comparison study of short titanium tapered
      stems has confirmed similar >99% survivorship in >1750 THA stems at 6- to 88
      (mean 36)-month follow-up. Early periprosthetic fracture, although rare (0.5%),
      was more likely to occur in older patients.

PMID- 24034509
TI  - A comparison of modular tapered versus modular cylindrical stems for complex
      femoral revisions.
AB  - The effect of distal geometry in modular stems in revision THA remains unclear.
      The purpose of this study is to compare femoral revisions with modular tapered
      versus modular cylindrical stems in high-grade defects. A multicenter review of
      105 femoral revisions with Paprosky III/IV defects using modular titanium stems
      (61 tapered; 44 cylindrical) was performed with an average follow-up of 5 years.
      Demographic data was comparable between groups. The tapered group had more IIIB
      and IV defects (51% vs. 20%; P < .01). The failure rate for component
      osseointegration was 1.6% in the tapered group and 15.9% in the cylindrical group
      (P = <.01). The rate of femoral component re-revision for any reason was 4.9% in
      the tapered group and 22.7% in the cylindrical group (P = .013). Modular tapered
      stems were associated with lower rates of stem failure and improved bone ongrowth
      compared to cylindrical stems despite being used in femurs with greater defects.

PMID- 24034510
TI  - An evaluation of the use of topical tranexamic acid in total knee arthroplasty.
AB  - The purpose of this study was to evaluate the effectiveness of topical tranexamic
      acid in primary TKA from a clinical and economic standpoint. We retrospectively
      reviewed 683 primary total knee arthroplasties performed at a single institution
      over a 2-year period. We compared 373 cases performed in 2010 without tranexamic
      acid to 310 cases performed in 2011 with tranexamic acid. Demographic data,
      hemoglobin levels, transfusion rates, hospital length of stay, cost, and
      perioperative complications during the first 3 months were collected. Statistical
      analysis was performed using two sample t-tests and Fisher's exact tests. There
      was no difference in age, sex, height, or pre-operative hemoglobin between the
      two groups. The tranexamic acid group had significantly higher post-operative
      hemoglobin (P<0.0001), lower transfusion rate (P<0.0001), decreased length of
      stay (P<0.0001), decreased blood bank costs (P<0.0001), increased pharmacy cost
      (P<0.0001), and decreased total direct cost to the hospital (P<0.0001). The
      average savings was approximately $1500 per patient. There were no differences in
      thromboembolic events or infection. The use topical tranexamic acid in primary
      TKA is safe, effective, and results in significant cost savings.

PMID- 24034511
TI  - Bundled payments for care improvement initiative: the next evolution of payment
      formulations: AAHKS Bundled Payment Task Force.
AB  - The Patient Protection and Affordable Care Act contains a number of provision for
      improving the delivery of healthcare in the United States, among the most
      impactful of which may be the call for modifications in the packaging of and
      payment for care that is bundled into episodes. The move away from fee for
      service payment models to payment for coordinated care delivered as comprehensive
      episodes is heralded as having great potential to enhance quality and reduce
      cost, thereby increasing the value of the care delivered. This effort builds on
      the prior experience around delivering care for arthroplasty under the Acute Care
      Episode Project and offers extensions and opportunities to modify the experience
      moving forward. Total hip and knee arthroplasties are viewed as ideal treatments
      to test the effectiveness of this payment model. Providers must learn the nuances
      of these modified care delivery concepts and evaluate whether their environment
      is conducive to success in this arena. This fundamental shift in payment for care
      offers both considerable risk and tremendous opportunity for physicians.
      Acquiring an understanding of the recent experience and the determinants of
      future success will best position orthopaedic surgeons to thrive in this new
      environment. Although this will remain a dynamic exercise for some time, early
      experience may enhance the chances for long term success, and physicians can
      rightfully lead the care delivery redesign process. 

PMID- 24034512
TI  - Daily glycaemic variability: benefits of optimal control.

PMID- 24034513
TI  - Do data in the literature indicate that glycaemic variability is a clinical
      problem? Glycaemic variability and vascular complications of diabetes.
AB  - In recent years glycaemic variability (GV) has emerged as a determinant of
      vascular complications of both type 1 and type 2 diabetes mellitus. In type 1
      diabetes analysis of data of GV show conflicting results on both micro- and macro
      vascular complications. In non-diabetic subjects blood glucose after loading is a
      stronger predictor of cardiovascular complications than fasting glucose. In type
      2 diabetes both coefficient of variation of fasting blood glucose and
      postprandial blood glucose predict cardiovascular events. Also, long term
      variability of HbA1c has been associated predominantly with diabetic nephropathy,
      less frequently with retinopathy. Intervention trials to evaluate the effect of
      postprandial glucose have been conducted only in prediabetes or in type 2
      diabetes and the data are not conclusive. In vitro and in vivo data have shown
      the mechanisms that are at the basis of the adverse cardiovascular effects of GV,
      mainly associated with oxidative stress; the atherogenic action of postprandial
      glucose also involves insulin sensitivity, postprandial increase in serum lipids
      and glycaemic index of food. Thus, correction of GV emerges as a target to be
      pursued in clinical practice in order to safely reduce mean blood glucose (and
      thus glycated haemoglobin) and for its direct effects on vascular complications
      of diabetes. 

PMID- 24034514
TI  - Which patients should be evaluated for blood glucose variability?
AB  - Diabetes is characterized by glycaemic disorders that include both sustained
      chronic hyperglycaemia and acute fluctuations (i.e. glycaemic variability).
      Increasing attention is being paid to the role of glycaemic variability as a
      relevant determinant for diabetes control and prevention of its vascular
      complications. As a consequence, it is strongly suggested that a global
      antidiabetic strategy should be aimed at reducing to a minimum the different
      components of glycaemic control (i.e. HbA1c, fasting and postprandial glucose, as
      well as glycaemic variability). Subjects at risk of hypoglycaemia, subjects with
      postprandial hyperglycaemia and patients who need to adjust or start insulin seem
      to be the categories that require glycaemic variability monitoring. The analysis
      of blood glucose variability represents an additional tool in the global
      assessment of glycaemic control and can serve as a guide to the clinician in the
      management of therapy and for the patients both in the prevention of acute
      complications, in particular hypoglycaemia, and chronic disease, in particular
      macrovascular complications. 

PMID- 24034515
TI  - How can we monitor glycaemic variability in the clinical setting?
AB  - No universal consensus exists on how to express glycaemic variability. Among
      other parameters, standard deviation of blood glucose values, mean amplitude of
      glycaemic excursions (MAGE), the Low Blood Glucose Index (LBGI) and the High
      Blood Glucose Index (HBGI), which were subsequently combined into the Average
      Daily Risk Range (ADRR), mean of daily differences (MODD) and glycaemic
      variability index (GVI) are highlighted. The continuous glucose monitoring in
      research and clinical settings has been a great help for a comprehensive approach
      to circadian blood glucose evaluation and identification of individual patterns,
      mainly in type 1 diabetes, but recently also in type 2 diabetes. In everyday
      clinical practice the judicious use of self-monitoring of blood glucose in an
      educational setting involving the patient and the care team is an unreplaceable
      tool to effectively and safely guide behavioural and drug therapy. 

PMID- 24034516
TI  - What are the preferred strategies for control of glycaemic variability in
      patients with type 2 diabetes mellitus?
AB  - The aim of therapy in type 2 diabetes in terms of blood glucose control is to
      reduce to target levels HbA1c and to reduce glycaemic variability in order to
      avoid both hypoglycaemia and wide excursions of postprandial glucose. The first
      approach to reduce glycaemic variability should consider a dietary and
      behavioural approach aiming to limit the glycaemic index and the glycaemic load
      of food and the prescription and implementation of a physical activity plan
      appropriate for the subject. From the pharmacological point of view, the diabetes
      specialist has now a much richer therapeutic armamentarium. The therapeutic
      algorithms can help the physician to choose the most appropriate drug. The
      traditional approach involves: i) metformin, acting mainly on fasting blood
      glucose; ii) sulphonylureas, that have shown a number of drawbacks, including the
      high risk of hypoglycemia; iii) pioglitazone, with a substantial effect on
      fasting and postprandial glucose and a low risk of hypoglycaemia; iv) insulin,
      that can be utilized with the basal or prandial approach. The new drugs belonging
      to the class of dipeptidyl peptidase-4 inhibitors have shown the reduction of
      postprandial glucose, a neutral effect on weight increase, a good safety profile
      and preliminary positive cardiovascular effects. When excess weight prevails, the
      glucagon-like peptide-1 agonists may be the preferred choice for their effect on
      weight reduction, reduction of hyperinsulinism and glycaemic variability. 

PMID- 24034517
TI  - Within-person reproducibility of urinary bisphenol A and phthalate metabolites
      over a 1 to 3 year period among women in the Nurses' Health Studies: a
      prospective cohort study.
AB  - BACKGROUND: Associations of bisphenol A and phthalates with chronic disease
      health outcomes are increasingly being investigated in epidemiologic studies. The
      majority of previous studies of within-person variability in urinary bisphenol A
      and phthalate metabolite concentrations have focused on reproducibility over
      short time periods. Long-term reproducibility data are needed to assess the
      potential usefulness of these biomarkers for prospective studies, particularly
      those examining risk of diseases with long latency periods. Low within-person
      reproducibility may attenuate relative risk estimates and reduce statistical
      power to detect associations with disease. Therefore, we assessed within-person
      reproducibility of bisphenol A, eight phthalate metabolites, and phthalic acid in
      spot urine samples over 1 to 3 years among women enrolled in two large cohort
      studies. METHODS: Women in the Nurses' Health Study and Nurses' Health Study II
      provided two spot urine samples, 1 to 3 years apart (n = 80 women for analyses of
      bisphenol A; n = 40 women for analyses of phthalate metabolites; n = 34 women for
      analyses of phthalic acid). To measure within-person reproducibility, we
      calculated Spearman rank correlation coefficients and intraclass correlation
      coefficients for creatinine-adjusted concentrations of bisphenol A, phthalate
      metabolites, and phthalic acid. RESULTS: Over 1 to 3 years, within-person
      variability of bisphenol A was high relative to total variability (intraclass
      correlation coefficient = 0.14) and rankings of bisphenol A levels between time
      points were weakly correlated (Spearman correlation = 0.19). Seven of the eight
      phthalate metabolites and phthalic acid demonstrated moderate within-person
      stability over time (Spearman correlation or intraclass correlation coefficient =
      0.39-0.55). Restricting analyses to first-morning urine samples did not alter
      results. CONCLUSIONS: Single measurements of bisphenol A in spot urine samples
      were highly variable within women over 1 to 3 years, indicating that
      investigation of associations between a single urinary bisphenol A measurement
      and disease risk may be challenging in epidemiologic studies. The majority of
      urinary phthalate metabolites and phthalic acid appeared moderately reproducible
      within women over time, suggesting single measurements may be useful in
      epidemiologic studies, although observed relative risks can be substantially
      attenuated.

PMID- 24034518
TI  - Influence of the 3K3A-activated protein C variant on the plasma clot lysis
      activity of t-PA and of t-PA on the variant's anticoagulant activity.

PMID- 24034520
TI  - The role of rotational forceps.

PMID- 24034521
TI  - Authors' response to: The role of rotational forceps.

PMID- 24034522
TI  - Statins in pregnancy: safety and perspectives of therapeutic applications.

PMID- 24034523
TI  - Authors' response to: Statins in pregnancy: safety and perspectives of
      therapeutic applications.

PMID- 24034524
TI  - Authors' response to: Factors influencing choice of surgical route of repair of
      genitourinary fistula, and the influence of route of repair on surgical outcomes:
      findings from a prospective cohort study.

PMID- 24034525
TI  - Factors influencing choice of surgical route of repair of genitourinary fistula,
      and the influence of route of repair on surgical outcomes: findings from a
      prospective cohort study.

PMID- 24034526
TI  - A report from #BlueJC: Can home biofeedback physiotherapy prevent fecal
      incontinence after third-degree tears?

PMID- 24034528
TI  - The Anopheles community and the role of Anopheles minimus on malaria transmission
      on the China-Myanmar border.
AB  - BACKGROUND: Malaria around the China-Myanmar border is a serious health problem
      in the countries of South-East Asia. An. minimus is a principle malaria vector
      with a wide geographic distribution in this area. Malaria is endemic along the
      boundary between Yunnan province in China and the Kachin State of Myanmar where
      the local Anopheles community (species composition) and the malaria transmission
      vectors have never been clarified. METHODS: Adult Anopheles specimens were
      collected using CDC light traps in four villages along the border of China and
      Myanmar from May 2012 to April 2013. Morphological and molecular identification
      of mosquito adults confirmed the species of Anopheles. Blood-meal identification
      using the female abdomens was conducted using multiplex PCR. For sporozoite
      detection in An. minimus, sets of 10 female salivary glands were pooled and
      identified with SSU rDNA using nested PCR. Monthly abundance of An. minimus
      populations during the year was documented. The diversity of Anopheles and the
      role of An. minimus on malaria transmission in this border area were analyzed.
      RESULTS: 4,833 adult mosquitoes in the genus Anopheles were collected and
      morphologically identified to species or species complex. The Anopheles community
      is comprised of 13 species, and 78.83% of our total specimens belonged to An.
      minimus s.l., followed by An. maculatus (5.55%) and the An. culicifacies complex
      (4.03%). The quantity of trapped An. minimus in the rainy season of malaria
      transmission was greater than during the non-malarial dry season, and a peak was
      found in May 2012. An. minimus fed on the blood of four animals: humans (79.8%),
      cattle (10.6%), pigs (5.8%) and dogs (3.8%). 1,500 females of An. minimus were
      pooled into 150 samples and tested for sporozoites: only 1 pooled sample was
      found to have sporozoites of Plasmodium vivax. CONCLUSION: Anopheles is abundant
      with An. minimus being the dominant species and having a high human blood index
      along the China-Myanmar border. The sporozoites in An. minimus were determined to
      be Plasmodium vivax with a 0.07-0.7% infection rate.

PMID- 24034529
TI  - Conflicting patterns of DNA barcoding and taxonomy in the cicada genus
      Tettigettalna from Southern Europe (Hemiptera: Cicadidae).
AB  - DNA barcodes have great potential to assist in species identification, especially
      when high taxonomical expertise is required. We investigated the utility of the
      5' mitochondrial cytochrome c oxidase I (COI) region to discriminate between 13
      European cicada species. These included all nine species currently recognized
      under the genus Tettigettalna, from which seven are endemic to the southern
      Iberian Peninsula. These cicadas have species-specific male calling songs but are
      morphologically very similar. Mean COI divergence between congeners ranged from
      0.4% to 10.6%, but this gene was proven insufficient to determine species limits
      within genus Tettigettalna because a barcoding gap was absent for several of its
      species, that is, the highest intraspecific distance exceeded the lowest
      interspecific distance. The genetic data conflicted with current taxonomic
      classification for T. argentata and T. mariae. Neighbour-joining and Bayesian
      analyses revealed that T. argentata is geographically structured (clades North
      and South) and might constitute a species complex together with T. aneabi and T.
      mariae. The latter diverges very little from the southern clade of T. argentata
      and shares with it its most common haplotype. T. mariae is often in sympatry with
      T. argentata but it remains unclear whether introgression or incomplete lineage
      sorting may be responsible for the sharing of haplotypes. T. helianthemi and T.
      defauti also show high intraspecific variation that might signal hidden cryptic
      diversity. These taxonomic conflicts must be re-evaluated with further studies
      using additional genes and extensive morphological and acoustic analyses. 

PMID- 24034530
TI  - Accomplishment of integrated management for renal replacement therapy in
      Portugal.

PMID- 24034531
TI  - Consideration of the JT interval rather than the QT interval.

PMID- 24034532
TI  - Flunarizine- and topiramate-associated depression responsive to mirtazapine.

PMID- 24034533
TI  - Kahlbaum's forms of catatonia.

PMID- 24034534
TI  - Symptom-inducibility in a case of conversion disorder.

PMID- 24034535
TI  - Pelvic pain in the presence of wandering spleen.

PMID- 24034536
TI  - Mullerian adenosarcoma: a frequently misinterpreted diagnosis.

PMID- 24034537
TI  - Ultrasound-guided aspiration and ethanol sclerotherapy (EST) for treatment of
      cyst recurrence in patients after previous endometriosis surgery: analysis of
      influencing factors using a decision tree.
AB  - STUDY OBJECTIVE: To evaluate the efficiency of transvaginal aspiration
      accompanied by ethanol sclerotherapy for treating cyst recurrence in patients who
      have previously undergone surgery to treat endometriosis and to analyze various
      factors that influence success rates using a data mining system. DESIGN:
      Retrospective cohort study (Canadian Task Force classification II-3). SETTING:
      Teaching hospital affiliated with Chang Gung University, Taoyuan, Taiwan.
      PATIENTS: One hundred ninety-six patients with endometrioma recurrence.
      INTERVENTION: A total of 274 transvaginal aspirations followed by sclerotherapy
      with 95% ethanol. Treatment times varied from immediate removal (0-10 minutes) to
      in situ retention. Patients were followed up at 3, 6, and 12 months to detect
      complications, determine the size and persistence of cysts, obtain the pelvic
      pain score, and assess for pregnancy or the need for repeat surgical
      intervention. A decision tree was used to determine factors from the collected
      data that most influenced the success of treatment. MEASUREMENTS AND MAIN
      RESULTS: Cyst size was consistently reduced until 6 months after ethanol
      sclerotherapy. The mean (SD) cyst reduction rate was 37.2% (42.2%), and the pain
      score reduction rate was 20.5% (71.5%). The antral follicle count was
      simultaneously increased by 36.4%. Sixty-three patients (23%) required repeated
      surgery during the observation period and were treated with either repeat
      aspiration (13.5%) or major laparoscopic or open laparotomic interventions
      (8.4%). Eighteen of 101 infertile patients (17.8%) achieved pregnancy. The total
      recovery rate (pregnancy or no persistence of symptoms or cyst) was significantly
      higher in patients in the groups that received longer treatment (7-10 minutes and
      retention) than in the groups with shorter treatment (0-6 minute) (47.0% vs
      28.7%; p < .005). The highest recovery rate was observed in patients with longer
      treatment time, smaller cysts (<=5.05 cm), lower CA 125 level (<=62.03 IU/mL),
      and fewer cysts (<=3 cm) (35 of 49 [71.4%]). In patients with larger cysts and
      cysts with clear contents, better success can be achieved with longer treatment.
      The use of postoperative ovarian suppression, traditional Chinese medicine, or no
      therapy for 6 months before the study was not significant among groups.
      CONCLUSION: Ultrasound-guided sclerotherapy with 95% ethanol retention is an
      effective alternative therapy for recurrent ovarian endometrioma, in particular
      in selected patient groups.

PMID- 24034538
TI  - Feasibility and optimal dosage of indocyanine green fluorescence for sentinel
      lymph node detection using robotic single-site instrumentation: preclinical
      study.
AB  - The present study was performed to determine the optimal dosage of indocyanine
      green (ICG) to accurately differentiate the sentinel node from surrounding tissue
      and then to test this dosage using novel single-port robotic instrumentation. The
      study was performed in healthy female pigs. After induction of anesthesia, all
      pigs underwent exploratory laparotomy, dissection of the bladder, and colpotomy
      to reveal the cervical os. With use of a 21-gauge needle, 0.5 mL normal saline
      solution was injected at the 3- and 9-o'clock positions as control. Four
      concentrations of ICG were constituted for doses of 1000, 500, 250, and 175 MUg
      per 0.5 mL. ICG was then injected at the 3- and 9-o'clock positions on the
      cervix. The SPY camera was used to track ICG into the sentinel nodes and to
      quantify the intensity of light emitted. SPY technology uses an intensity scale
      of 1 to 256; this scale was used to determine the difference in intensity between
      the sentinel node and surrounding tissues. The optimal dosage was tested using
      single-port robotic instrumentation with the same injection techniques. A
      sentinel node was identified at all doses except 175 MUg, at which ICG stayed in
      the cervix and vasculature only. For both the 500- and 250-MUg doses, the
      sentinel node was identified before reaching maximum intensity. At maximum
      intensity, the difference between the surrounding tissue and the node was 207
      (251 vs 44) for the 500-MUg dose and 159 (251 vs 92) for the 250-MUg dose.
      Sentinel lymph node (SLN) biopsy was successfully performed using single-port
      robotic technology with both the 250- and 500-MUg doses. For SLN detection, the
      dose of ICG is related to the ability to differentiate the sentinel node from the
      surrounding tissue. An ICG dose of 250 to 500 MUg enables identification of a SLN
      with more distinction from the surrounding tissues, and this procedure is
      feasible using single-port robotics instrumentation. 

PMID- 24034539
TI  - Diagnosis and management of intramural ectopic pregnancy.
AB  - Intramural pregnancy, a gestation completely surrounded by the myometrium located
      within the uterine wall with separation from the uterine cavity, is an extremely
      unusual form of pregnancy. Complications resulting from intramural pregnancy
      include inevitable uterine rupture with resultant hemorrhage and possible
      hysterectomy if diagnosis is not made early and treatment is not initiated. An
      asymptomatic patient was initially diagnosed with a missed abortion at
      approximately 6 weeks of gestation after a routine ultrasound. Suction curettage
      was performed approximately 1 month after the initial diagnosis. The pathology
      specimen failed to reveal placental villi. Ultimately, the diagnosis of
      intramural pregnancy was made via ultrasound and a computed tomography scan. She
      was treated with a single dose of systemically administered methotrexate. Over a
      period of 4 months, beta-human chorionic gonadotropin levels trended downward;
      however, the intramural pregnancy failed to resolve completely, and a persistent
      mass remained. The intramural pregnancy was removed using the da Vinci
      laparoscopic procedure (Intuitive Surgical, Sunnyvale, CA). If the diagnosis of
      intramural ectopic pregnancy is made sufficiently early, conservative measures
      can be taken, which can preserve a patient's future fertility. 

PMID- 24034540
TI  - Laparoendoscopic single-site surgery for management of adnexal masses in
      pregnancy: case series.
AB  - The incidence of adnexal masses in pregnancy is estimated to be 1% to 4%. In
      select cases, surgical intervention is required. Recent studies have demonstrated
      that laparoscopy during pregnancy is safe and confers many advantages over
      laparotomy. Herein we present a series of nine cases collected prospectively that
      demonstrate the feasibility, safety, and putative benefits of laparoendoscopic
      single-site surgery for treatment of adnexal masses in pregnant women. 

PMID- 24034541
TI  - Re: hysteroscopy metroplasty for the septate uterus: review and meta-analysis.

PMID- 24034542
TI  - Reply:.

PMID- 24034543
TI  - High patient satisfaction after inflatable penile prostheses implantation
      correlates with female partner satisfaction.
AB  - INTRODUCTION: Patient and female partner satisfaction after implantation of an
      inflatable penile prosthesis (IPP) assessed by objective means, and the
      correlation between the partners, is important for determining postoperative
      sexual life. AIM: The primary goal was to evaluate patients' erectile function
      and patients' and their partners' satisfaction after IPP implantation. A
      secondary aim was to investigate potential determinative factors of satisfaction
      according to device characteristics, demographics, and cause of erectile
      dysfunction (ED). METHODS: Ninety patients, who underwent IPP implantation as an
      alternative to refractory or undesirable medical treatment for ED, were
      evaluated. Patients who could not or refused to participate, or were out of a
      relationship, were excluded. The 69 remaining patients were evaluated for their
      pre- and postoperative erectile function and posttreatment satisfaction for
      themselves and their partners. MAIN OUTCOME MEASURES: Preoperative and
      postoperative scores on the International Index of Erectile Function
      Questionnaire-five items (IIEF-5) were compared. The Erectile Dysfunction
      Inventory of Treatment Satisfaction (EDITS) was given to males and their female
      partners. Patient demographics, etiology of ED, and implant characteristics were
      correlated also with patients' EDITS scores. RESULTS: Mean IIEF-5 scores
      demonstrated a significant improvement after IPP implantation: from 8.88+/-3.75
      to 20.97+/-4.37 (P<0.001). The mean patients' EDITS score was 75.48+/-20.54,
      whereas mean female partners' score was 70.00+/-22.92, highlighting high
      posttreatment satisfaction for both. Regression analysis suggested a direct
      linear correlation of satisfaction between the sexual partners as a degree of
      satisfaction. There were no statistically significant differences according to
      level of education or implant characteristics. Concerning the etiology of ED, no
      conclusions could be made. CONCLUSIONS: Overcoming previous limitations in
      determining post-IPP implantation satisfaction, our study reiterates high rates
      of patient and partner satisfaction. Of particular note, patient satisfaction
      appears independent of prosthesis type and cylinder length.

PMID- 24034545
TI  - Additional value of adenosine-stress dynamic CT myocardial perfusion imaging in
      the reclassification of severity of coronary artery stenosis at coronary CT
      angiography.
AB  - AIM: To assess the additional value of adenosine-stress dynamic computed
      tomography (CT) perfusion (ASDCTP) imaging compared with coronary CT angiography
      (CCTA) alone to detect significant coronary artery stenosis for each threshold of
      50% and 70% diameter stenosis. MATERIALS AND METHODS: The study included 34
      patients (65 +/- 11 years, 79% men) with suspected coronary artery diseases who
      underwent ASDCTP imaging using a 128-section dual-source CT (DSCT) and invasive
      coronary angiography (ICA). Two investigators classified coronary artery stenosis
      on CCTA as severe or not. If appropriate image quality could not be acquired due
      to artefacts, the segment was classified as a lesion with significant stenosis.
      After the interpretation of ASDCTP imaging, the degree of stenosis was
      reclassified. All parameters of diagnostic accuracy were calculated before and
      after ASDCTP analysis for detection of significant coronary artery stenosis with
      ICA as the reference standard. RESULTS: The diagnostic accuracy parameters per
      vessel for the detection of >=50% stenosis before and after ASDCTP analysis
      changed as follows: sensitivity, from 80% to 83%; specificity, from 83% to 98%;
      positive predictive value (PPV), from 87% to 98%; and negative predictive value
      (NPV), from 75% to 80%. The addition of ASDCTP resulted in reclassification from
      one class of stenosis severity to another in a significant number of vessels with
      threshold of 50% stenosis [net reclassification improvement (NRI), 0.176; p <
      0.01]. Conversely, the addition of ASDCTP did not result in significant
      reclassification of stenosis severity in vessels with threshold of 70% stenosis
      (NRI, 0.034; p = 0.51). CONCLUSIONS: ASDCTP imaging provides incremental value in
      the detection of significant coronary artery stenosis using a threshold of 50%.

PMID- 24034544
TI  - Behavioral metabolomics analysis identifies novel neurochemical signatures in
      methamphetamine sensitization.
AB  - Behavioral sensitization has been widely studied in animal models and is
      theorized to reflect neural modifications associated with human psychostimulant
      addiction. While the mesolimbic dopaminergic pathway is known to play a role, the
      neurochemical mechanisms underlying behavioral sensitization remain incompletely
      understood. In this study, we conducted the first metabolomics analysis to
      globally characterize neurochemical differences associated with behavioral
      sensitization. Methamphetamine (MA)-induced sensitization measures were generated
      by statistically modeling longitudinal activity data for eight inbred strains of
      mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography
      mass spectrometry profiling was performed on 48 brain samples, yielding 301
      metabolite levels per sample after quality control. Association testing between
      metabolite levels and three primary dimensions of behavioral sensitization (total
      distance, stereotypy and margin time) showed four robust, significant
      associations at a stringent metabolome-wide significance threshold (false
      discovery rate, FDR <0.05). Results implicated homocarnosine, a dipeptide of GABA
      and histidine, in total distance sensitization, GABA metabolite 4
      guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol
      in margin time sensitization. Secondary analyses indicated that these
      associations were independent of concurrent MA levels and, with the exception of
      the myo-inositol association, suggest a mechanism whereby strain-based genetic
      variation produces specific baseline neurochemical differences that substantially
      influence the magnitude of MA-induced sensitization. These findings demonstrate
      the utility of mouse metabolomics for identifying novel biomarkers, and
      developing more comprehensive neurochemical models, of psychostimulant
      sensitization.

PMID- 24034546
TI  - Differentiation between intramedullary spinal ependymoma and astrocytoma:
      comparative MRI analysis.
AB  - AIM: To investigate magnetic resonance imaging (MRI) findings that could be used
      to differentiate intramedullary spinal ependymoma from astrocytoma, and to
      determine predictors for this differentiation. MATERIALS AND METHODS: MRI images
      of 43 consecutive patients with pathologically proven intramedullary spinal
      ependymoma (n = 24) and astrocytoma (n = 19) were comparatively evaluated with
      regard to size, location, margin, signal intensity, contrast enhancement,
      presence of syringohydromyelia, tumoural cyst, non-tumoural cyst, and
      haemorrhage. MRI findings and demographic data were compared between the two
      tumour groups using univariate and multivariate logistic regression analyses.
      RESULTS: In patients with ependymoma, older age and a larger solid component were
      more often observed than in astrocytoma. Central location, presence of
      enhancement, diffuse enhancement, syringohydromyelia, haemorrhage, and cap sign
      were more frequently observed in ependymoma. However, multivariate analysis
      revealed that syringohydromyelia was the only variable able to independently
      differentiate ependymoma from astrocytoma, with an odds ratio of 62.9 (95% CI:
      4.38-903.22; p = 0.002). CONCLUSION: Among the various findings, the presence of
      syringohydromyelia is the main factor distinguishing ependymoma from astrocytoma.

PMID- 24034547
TI  - Spinal neural tube defects on in utero MRI.
AB  - Spinal neural tube defects are a heterogeneous group of disorders, which remain
      relatively common, with a prevalence of 1-2 per 1000 live births despite advances
      in maternal antenatal care. They range from mild disorders with limited
      neurodevelopmental sequelae to extensive abnormalities with significant morbidity
      and mortality. The advent of in utero magnetic resonance imaging has enabled
      accurate anatomical characterization of an increasing number of abnormalities
      with increasing confidence. Recognition of the salient radiological features of
      these disorders and their relationship to the embryogenesis of the spinal cord
      and its coverings is now possible. This review describes the radiological
      appearances of these disorders with examples from Fetal Imaging Unit, University
      of Sheffield to illustrate the key anatomical and radiological features to aid
      the radiologist in their recognition. 

PMID- 24034548
TI  - Prospective MRI assessment for invasive lobular breast cancer. Correlation with
      tumour size at histopathology and influence on surgical management.
AB  - AIM: To evaluate the performance of breast magnetic resonance imaging (MRI) in
      determining the size of invasive lobular carcinoma (ILC) compared to
      histopathology, and its influence on breast surgical management. MATERIALS AND
      METHODS: Prospective evaluation was undertaken of standardized contrast-enhanced
      MRI images of 51 consecutive women over an 18 month period with pure ILC or with
      lobular features as the dominant subtype on breast core biopsy. Image
      interpretation was performed by one consultant radiologist (M.H.). The lesion
      size at MRI was compared with the size at final histopathology after surgical
      excision using a Bland-Altman agreement plot. RESULTS: Of the 51 prospectively
      imaged consecutive women, seven were excluded as they had diffuse ILC. The
      remaining 44 patients had a mean histological tumour size of 34.9 mm (range 4-77
      mm). MRI underestimated tumour size in 26 (59.1%) cases. In 21 (47.7%) patients,
      this discrepancy was small, ranging up to 16 mm. The largest underestimation
      occurred in five (11.4%) cases with a difference ranging between 31 and 48 mm.
      Fifteen (34.1%) tumours were overestimated by MRI where the discrepancy ranged up
      to 22 mm. In three (6.8%) patients MRI and histological size matched. The Bland
      Altman agreement plot demonstrated that in 95% of cases the size at
      histopathology will be between 0.36 and 2.31 times the MRI size at extremes. MRI
      correlated better with histopathology in tumours up to T2 (<5 cm) size leading to
      a change in surgical management for nine of the 44 (20.5%) patients. CONCLUSION:
      MRI enables surgical management decisions to be made with increased confidence in
      patients with ILC up to T2 size.

PMID- 24034549
TI  - Diffusion-weighted MRI of hepatocellular carcinoma in cirrhosis.
AB  - The internationally accepted diagnostic criteria for hepatocellular carcinoma
      (HCC) in cirrhosis are highly accurate for large tumours, but offer relatively
      low sensitivity for small (<2 cm) tumours. Diffusion-weighted imaging (DWI) is a
      functional magnetic resonance imaging (MRI) technique that has been studied
      extensively as an aid to visualize various abdominal malignancies, including HCC
      in cirrhosis. DWI maps water diffusivity, which in HCC may be restricted as a
      result of changes ensuing from hepatocarcinogenesis. The present review is based
      on up-to-date evidence and describes the strengths and weaknesses of DWI, both as
      a standalone technique and as an adjunct sequence to conventional protocols, in
      the diagnosis, staging, prognostication, and assessment of treatment response of
      HCC in cirrhosis.

PMID- 24034550
TI  - Imaging of the aortic valve with MRI and CT angiography.
AB  - The aortic valve may be affected by a wide range of congenital and acquired
      diseases. Echocardiography is the main non-invasive imaging technique for
      assessing patho-anatomical alterations of the aortic valve and adjacent
      structures and in many cases is sufficient to establish a diagnosis and/or guide
      treatment decisions. Recent technological advances in magnetic resonance imaging
      (MRI) and multidetector computed tomography (MDCT) have enabled these techniques
      to play a complimentary role in certain clinical scenarios and as such can be
      useful problem-solving tools. Radiologists should be familiar with the
      indications, advantages, and limitations of MRI and MDCT in order to advise and
      direct an appropriate imaging strategy depending upon the clinical scenario. This
      article reviews the role of MRI and MDCT angiography for assessment of the aortic
      valve including relevant anatomy, scan acquisition protocols, and post-processing
      methods. An approach to interpretation and the key imaging features of commonly
      encountered aortic valvular diseases are discussed. 

PMID- 24034551
TI  - Post-traumatic heterotopic ossification of distal tibiofibular syndesmosis
      mimicking a surface osteosarcoma.
AB  - AIM: To present the imaging features of post-traumatic heterotopic ossification
      (HO) of the distal tibiofibular syndesmosis initially suspected to be a surface
      osteosarcoma. MATERIALS AND METHODS: A retrospective review was conducted of the
      presenting complaint and imaging features of patients with a final diagnosis of
      HO referred over an 8 year period to a specialist orthopaedic oncology centre.
      RESULTS: Five patients with HO were identified. All were adult males with an age
      range of 19-41 years. There was a history of prior ankle trauma in all cases but
      the significance was not recognized at the time of referral to the specialist
      centre. There was radiographic evidence of HO arising from the inner aspects of
      the distal tibia and fibula approximately 3 cm proximal to the ankle joint. The
      HO was "kissing" in two cases and partially fused (synostosis) in two. The HO in
      the fifth case was arising on the inner fibular cortex alone. Magnetic resonance
      imaging (MRI), available in four cases, showed predominantly low signal intensity
      due to the dense bone formation. CONCLUSION: The history of prior ankle trauma
      with ossification arising from the inner aspects of both the distal tibia and
      fibula is typical of post-traumatic HO and distinguish this benign condition from
      the rare surface osteosarcoma at this site.

PMID- 24034552
TI  - The SECCA procedure for faecal incontinence: a review.
AB  - AIM: The SECCA system is a treatment option for patients with faecal incontinence
      and was introduced into clinical practice in 2002. Clinical studies of
      radiofrequency energy to treat patients with faecal incontinence have been
      published. This article aimed to review all published series to assess the
      results of this treatment. METHOD: Twelve studies were included. Outcomes
      analysed included quality of life, the Wexner incontinence score, anorectal
      manometry and endoanal ultrasound findings. RESULTS: A total of 220 patients from
      10 studies were included. In the majority of clinical studies, the SECCA
      procedure has been shown to be an effective treatment of mild-to-moderate faecal
      incontinence. CONCLUSION: When patient selection is appropriate, this treatment
      has demonstrated clinically significant improvements in symptoms, as demonstrated
      by statistically significant reductions in the Wexner incontinence and quality of
      life scores.

PMID- 24034554
TI  - Etiology of Alzheimer's disease: kinetic, thermodynamic and fluorimetric analyses
      of interactions of pseudo Abeta-peptides with neuronal nitric oxide synthase.
AB  - Aggregated beta-amyloid deposit is a hallmark in the neuropathology of
      Alzheimer's disease but their mechanism of formation still remains unresolved.
      Previously we reported that a normal pentapeptide Abeta(17-21) and glycine zipper
      peptide Abeta(29-33) strongly inhibited nitric oxide synthase and rapidly
      initiated fibrillogenesis. Critical amino acids within these fragments were not
      identified. We now report on the interaction of four pseudo-peptides with nNOS -
      two peptides with a reversed amino acid sequence [Abeta(17-21r); Abeta(29-33r)]
      and two peptides with Phe19, Phe20 and Ile31, Ile32 substituted with polar
      glutamic acid [Abeta(17-21p); Abeta(29-33p)]. It was shown that while the
      inhibitor constants (Ki) increased 2-3 fold for each of the pseudo-peptides when
      compared with the normal peptides the dissociation constant Kd increased between
      20 and 50 fold. Stern-Volmer fluorescence quenching constants (K(SV)) for
      Abeta(17-21p) and Abeta(29-33p) were 7.2*10(-3) and 6.1*10(-3) MUM(-1)
      respectively at 298 K some 2-3 fold lower than the corresponding Abeta(17-21r);
      Abeta(29-33r). With temperature increase there was an increase in K(SV) and Kd,
      suggesting a dynamic quenching mechanism. Thermodynamic parameters, DeltaH,
      DeltaS and DeltaG were all positive indicating endothermic, non-spontaneous,
      hydrophobic-hydrophobic associations of the pseudo-peptides with the enzyme. By
      FRET analysis the efficiency of fluorescence transfer between enzyme tryptophans
      and the pseudo-peptides was 90% (compared to 97% for the natural substrate). The
      distance the tryptophans moved after interaction with Abeta(17-21r) and Abeta(17
      21p) was 10% greater, while for Abeta(29-33r) and Abeta(29-33p) it was 20-25%
      greater, than with the normal peptides; the fluorescence intensity was 20-75%
      higher. This increase in distance, fluorescent intensity and transfer efficiency
      illustrate an increase in interaction energy for the pseudo-peptides with nNOS
      lending support for the strategic position of the Phe19, Phe20, Ile31 and Ile32
      in the original peptides not only for inhibition of the nNOS but for initiation
      of fibrillogenesis.

PMID- 24034553
TI  - Age at first introduction to complementary foods is associated with
      sociodemographic factors in children with increased genetic risk of developing
      type 1 diabetes.
AB  - Infant's age at introduction to certain complementary foods (CF) has in previous
      studies been associated with islet autoimmunity, which is an early marker for
      type 1 diabetes (T1D). Various maternal sociodemographic factors have been found
      to be associated with early introduction to CF. The aims of this study were to
      describe early infant feeding and identify sociodemographic factors associated
      with early introduction to CF in a multinational cohort of infants with an
      increased genetic risk for T1D. The Environmental Determinants of Diabetes in the
      Young study is a prospective longitudinal birth cohort study. Infants (N = 6404)
      screened for T1D high risk human leucocyte antigen-DQ genotypes (DR3/4, DR4/4,
      DR4/8, DR3/3, DR4/4, DR4/1, DR4/13, DR4/9 and DR3/9) were followed for 2 years at
      six clinical research centres: three in the United States (Colorado,
      Georgia/Florida, Washington) and three in Europe (Sweden, Finland, Germany). Age
      at first introduction to any food was reported at clinical visits every third
      month from the age of 3 months. Maternal sociodemographic data were self-reported
      through questionnaires. Age at first introduction to CF was primarily associated
      with country of residence. Root vegetables and fruits were usually the first CF
      introduced in Finland and Sweden and cereals were usually the first CF introduced
      in the United States. Between 15% and 20% of the infants were introduced to solid
      foods before the age of 4 months. Young maternal age (<25 years), low educational
      level (<12 years) and smoking during pregnancy were significant predictors of
      early introduction to CF in this cohort. Infants with a relative with T1D were
      more likely to be introduced to CF later. 

PMID- 24034555
TI  - Rings B,D-seco limonoid antifeedants from Swietenia mahogani.
AB  - Three phragmalin-type limonoids, swietephragmin H (1), swietephragmin I (2) and
      11-hydroxyswietephragmin B (3), and a mexicanolide-type limonoid 2-hydroxy-6
      deacetoxyswietenine (4), together with known compounds, 6-O-acetyl-2
      hydroxyswietenin (5), 2-hydroxyswietenine (6), swietemahonin G (7), methyl 6
      hydroxyangolensate (8) and 7-deacetoxy-7-oxogedunin (9) were isolated from the
      leaves of Swietenia mahogani (Meliaceae). Their structures were established by
      extensive NMR experiments in conjunction with mass spectrometry. The antifeedant
      activity of the isolated compounds was evaluated. 

PMID- 24034556
TI  - Geospatial association of endemicity of ataxic polyneuropathy and highly
      cyanogenic cassava cultivars.
AB  - BACKGROUND: Exposure to cyanide from cassava foods is present in communities
      where ataxic polyneuropathy is endemic. Ataxic polyneuropathy is endemic in
      coastal parts of southwest and southeast Nigeria, and coastal Newala, south
      India, but it has been reported in epidemic or endemic forms from Africa, Asia,
      or Caribbean. This study was done to determine if cyanogenicity of cassava
      cultivars is higher in lowland than highland areas, and if areas of endemicity of
      ataxic polyneuropathy colocalize with areas of highest cyanogenicity of cassava.
      METHODS: Roots of cassava cultivars were collected from 150 farmers in 32 of 37
      administrative areas in Nigeria. Global positioning system was used to determine
      the location of the roots. Roots were assayed for concentrations of cyanogens.
      Thin Plate Spline regression was used to produce the contour map of cyanogenicity
      of the study area. Contour maps of altitude of the endemic areas were produced.
      Relationship of cyanogenicity of cassava cultivars and altitude, and of locations
      of areas of high cyanogenicity and areas of endemicity were determined. RESULTS:
      Geometrical mean (95% CI) cyanogen concentration was 182 (142-233) mg HCN eq/kg
      dry wt for cassava cultivars in areas <= 25 m above sea level, but 54 (43-66) mg
      HCN eq/kg dry wt for areas > 375 m. Non-spatial linear regression of altitude on
      logarithm transformed concentrations of cyanogens showed highly significant
      association, (p < 0.0001). Contour map of concentrations of cyanogens in cassava
      cultivars in Nigeria showed four areas with average concentrations of cassava
      cyanogens > 250 mg HCN eq/kg dry wt, and one area of moderately high cyanogen
      concentration > 150 mg HCN eq/kg dry wt. The endemic areas colocalized with areas
      of highest cassava cyanogenicity in lowland areas close to the Atlantic Ocean.
      CONCLUSION: This study shows strong geospatial association of areas of endemicity
      of ataxic polyneuropathy and areas of highest cyanogenicity of cassava cultivars.
      Finding of higher cyanogenicity of cassava in lowland than highland areas
      indicate strong influence of altitude on expression of cyanogens in cassava
      cultivars.

PMID- 24034557
TI  - Genomewide screening for genes involved in biofilm formation and miconazole
      susceptibility in Saccharomyces cerevisiae.
AB  - Infections related to fungal biofilms are difficult to treat due to the reduced
      susceptibility of sessile cells to most antifungal agents. Previous research has
      shown that 1-10% of sessile Candida cells survive treatment with high doses of
      miconazole (a fungicidal imidazole). The aim of this study was to identify genes
      involved in fungal biofilm formation and to unravel the mechanisms of resistance
      of these biofilms to miconazole. To this end, a screening of a Saccharomyces
      cerevisiae deletion mutant bank was carried out. Our results revealed that genes
      involved in peroxisomal transport and the biogenesis of the respiratory chain
      complex IV play an essential role in biofilm formation. On the other hand, genes
      involved in transcription and peroxisomal and mitochondrial organization seem to
      highly influence the susceptibility to miconazole of yeast biofilms.
      Additionally, our data confirm previous findings on genes involved in biofilm
      formation and in general stress responses. Our data suggest the involvement of
      peroxisomes in biofilm formation and miconazole resistance in fungal biofilms. 

PMID- 24034558
TI  - Structure-activity relationship analysis of curcumin analogues on anti-influenza
      virus activity.
AB  - Curcumin (Cur) is a commonly used colouring agent and spice in food. Previously,
      we reported that Cur inhibits type A influenza virus (IAV) infection by
      interfering with viral haemagglutination (HA) activity. To search for a stable
      Cur analogue with potent anti-IAV activity and to investigate the structure
      contributing to its anti-IAV activity, a comparative analysis of structural and
      functional analogues of Cur, such as tetrahydrocurcumin (THC) and petasiphenol
      (Pet), was performed. The result of time-of-drug addition tests indicated that
      these curcuminoids were able to inhibit IAV production in cell cultures.
      Noticeably, Pet and THC inhibit IAV to a lesser extent than Cur, which is in line
      with their effect on reducing plaque formation when IAV was treated with Cur
      analogues before infection. Unexpectedly, both THC and Pet did not harbour any HA
      inhibitory effect. It should be noted that the structure of Pet and THC differs
      from Cur with respect to the number of double bonds present in the central seven
      carbon chain, and structure modelling of Cur analogues indicates that the
      conformations of THC and Pet are distinct from that of Cur. Moreover, simulation
      docking of Cur with the HA structure revealed that Cur binds to the region
      constituting sialic acid anchoring residues, supporting the results obtained by
      the inhibition of HA activity assay. Collectively, structure-activity
      relationship analyses indicate that the presence of the double bonds in the
      central seven-carbon chain enhanced the Cur -dependent anti-IAV activity and also
      that Cur might interfere with IAV entry by its interaction with the receptor
      binding region of viral HA protein.

PMID- 24034559
TI  - Classical swine fever virus triggers RIG-I and MDA5-dependent signaling pathway
      to IRF-3 and NF-kappaB activation to promote secretion of interferon and
      inflammatory cytokines in porcine alveolar macrophages.
AB  - BACKGROUND: Classical swine fever (CSF) caused by CSF virus (CSFV) is a highly
      contagious disease of pigs. The RNA helicases retinoic acid-inducible gene I (RIG
      I) and melanoma differentiation-associated gene 5 (MDA-5) are differentially
      involved in the detection of various RNA viruses. In present study, we
      investigated the roles of RIG-I and MDA-5 in eliciting antiviral and inflammatory
      responses to CSFV shimen strain in Porcine alveolar macrophages (PAMs). METHODS:
      CSFV Shimen strain was used as challenge virus in this study and PAMs were
      cultured in vitro. Interferon regulatory factor (IRF)-3 and nuclear factor-kappa
      B (NF-kappaB) translocation was detected using immunofluorescent staining; RIG-I,
      MDA5, interferon promoter-stimulating factor 1 (IPS-1), IRF-3 and NF-kappaB
      expression was measured by Western Blotting; Interferon beta (IFN-beta), IFN
      alpha, interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor (TNF-alpha)
      expression was tested by Enzyme-linked immunosorbent assays (ELISA) and shRNA
      mediated knockdown of MDA5 or RIG-I was performed. RESULTS: The findings
      suggested that the initial response to CSFV infection resulted in the higher
      expression of RIG-I and MDA5 leading to the activation of IPS-1, IRF-3 and NF
      kappaB in a dose-dependent manner. Evaluation of IFN-alpha, IFN-beta, IL-1beta,
      IL-6 or TNF-alpha expressed by PAMs showed significant differences between
      infected and uninfected cells. CSFV infected cells induced to express high levels
      of IFN-alpha, IFN-beta, IL-1beta, IL-6 and TNF-alpha in a dose-dependent way
      within 24 h post-infection (hpi). At the same time, CSFV improved the nuclear
      translocation of IRF-3 and NF-kappaB. We also directly compared and assessed the
      roles of RIG-I and MDA5 in triggering innate immune actions during CSFV infection
      through shRNA-mediated knockdown of MDA5 or RIG-I. We found that, compared to the
      control, the production of IFN-alpha, IFN-beta, IL-1beta, IL-6 and TNF-alpha in
      response to CSFV infection was heavily reduced in RIG-I knockdown cells while it
      was moderately decreased in MDA5 knockdown cells. PAMs derived from knockdown of
      both RIG-I and MDA5 almost failed to produce IFNs and inflammatory cytokines.
      CONCLUSIONS: It indicates that CSFV can be recognized by both RIG-I and MDA5 to
      initiate the RIG-I signaling pathway to trigger innate defenses against
      infection.

PMID- 24034560
TI  - Predictions of CD4 lymphocytes' count in HIV patients from complete blood count.
AB  - BACKGROUND: HIV diagnosis, prognostic and treatment requires T CD4 lymphocytes'
      number from flow cytometry, an expensive technique often not available to people
      in developing countries. The aim of this work is to apply a previous developed
      methodology that predicts T CD4 lymphocytes' value based on total white blood
      cell (WBC) count and lymphocytes count applying sets theory, from information
      taken from the Complete Blood Count (CBC). METHODS: Sets theory was used to
      classify into groups named A, B, C and D the number of leucocytes/mm3,
      lymphocytes/mm3, and CD4/MUL3 subpopulation per flow cytometry of 800 HIV
      diagnosed patients. Union between sets A and C, and B and D were assessed, and
      intersection between both unions was described in order to establish the
      belonging percentage to these sets. Results were classified into eight ranges
      taken by 1000 leucocytes/mm3, calculating the belonging percentage of each range
      with respect to the whole sample. RESULTS: Intersection (A ? C) ? (B ? D) showed
      an effectiveness in the prediction of 81.44% for the range between 4000 and 4999
      leukocytes, 91.89% for the range between 3000 and 3999, and 100% for the range
      below 3000. CONCLUSIONS: Usefulness and clinical applicability of a methodology
      based on sets theory were confirmed to predict the T CD4 lymphocytes' value,
      beginning with WBC and lymphocytes' count from CBC. This methodology is new,
      objective, and has lower costs than the flow cytometry which is currently
      considered as Gold Standard.

PMID- 24034561
TI  - Factors influencing detection of eDNA from a stream-dwelling amphibian.
AB  - Environmental DNA (eDNA) methods for detecting and estimating abundance of
      aquatic species are emerging rapidly, but little is known about how processes
      such as secretion rate, environmental degradation, and time since colonization or
      extirpation from a given site affect eDNA measurements. Using stream-dwelling
      salamanders and quantitative PCR (qPCR) analysis, we conducted three experiments
      to assess eDNA: (i) production rate; (ii) persistence time under different
      temperature and light conditions; and (iii) detectability and concentration
      through time following experimental introduction and removal of salamanders into
      previously unoccupied streams. We found that 44-50 g individuals held in aquaria
      produced 77 ng eDNA/h for 2 h, after which production either slowed considerably
      or began to equilibrate with degradation. eDNA in both full-sun and shaded
      treatments degraded exponentially to <1% of the original concentration after 3
      days. eDNA was no longer detectable in full-sun samples after 8 days, whereas
      eDNA was detected in 20% of shaded samples after 11 days and 100% of refrigerated
      control samples after 18 days. When translocated into unoccupied streams,
      salamanders were detectable after 6 h, but only when densities were relatively
      high (0.2481 individuals/m(2) ) and when samples were collected within 5 m of the
      animals. Concentrations of eDNA detected were very low and increased steadily
      from 6-24 h after introduction, reaching 0.0022 ng/L. Within 1 h of removing
      salamanders from the stream, eDNA was no longer detectable. These results suggest
      that eDNA detectability and concentration depend on production rates of
      individuals, environmental conditions, density of animals, and their residence
      time. 

PMID- 24034562
TI  - Phase I study evaluating the treatment of patients with locally advanced
      pancreatic cancer with carbon ion radiotherapy: the PHOENIX-01 trial.
AB  - BACKGROUND: Treatment options for patients with locally advanced pancreatic
      cancer include surgery, chemotherapy as well as radiotherapy. In many cases,
      surgical resection is not possible, and therefore treatment alternatives have to
      be performed. Chemoradiation has been established as a convincing treatment
      alternative for locally advanced pancreatic cancer. Carbon ions offer physical
      and biological characteristics. Due to their inverted dose profile and the high
      local dose deposition within the Bragg peak precise dose application and sparing
      of normal tissue is possible. Moreover, in comparison to photons, carbon ions
      offer an increased relative biological effectiveness (RBE), which can be
      calculated between 1.16 and 2.46 depending on the pancreatic cancer cell line as
      well as the endpoint analyzed. Japanese Data on the evaluation of carbon ion
      radiation therapy showed promising results for patients with pancreatic cancer.
      METHODS AND DESIGN: The present PHOENIX-01 trial evaluates carbon ion
      radiotherapy using the active rasterscanning technique in patients with advanced
      pancreatic cancer in combination with weekly gemcitabine and adjuvant
      gemcitabine. Primary endpoint is toxicity, secondary endpoints are overall
      survival, progression-free survival and response. DISCUSSION: The physical and
      biological properties of the carbon ion beam promise to improve the therapeutic
      ratio in patients with pancreatic cancer: Due to the inverted dose profile dose
      deposition in the entry channel of the beam leads to sparing of normal tissue;
      the Bragg peak can be directed into the defined target volume, and the sharp dose
      fall-off thereafter again spares normal tissue behind the target volume. The
      higher RBE of carbon ions, which has been shown also for pancreatic cancer cell
      lines in the preclinical setting, is likely to contribute to an increase in local
      control, and perhaps in OS. Early data from Japanese centers have shown promising
      results. In conclusion, this is the first trial to evaluate actively delivered
      carbon ion beams in patients with locally advanced pancreatic cancer within a
      dose-escalation strategy. TRIAL REGISTRATION: NCT01795274.

PMID- 24034563
TI  - Maternal exposure to heatwave and preterm birth in Brisbane, Australia.
AB  - OBJECTIVE: To quantify the short-term effects of maternal exposure to heatwave on
      preterm birth. DESIGN: An ecological study. SETTING: A population-based study in
      Brisbane, Australia. POPULATION: All pregnant women who had a spontaneous
      singleton live birth in Brisbane between November and March in 2000-2010 were
      studied. METHODS: Daily data on pregnancy outcomes, meteorological factors, and
      ambient air pollutants were obtained. The Cox proportional hazards regression
      model with time-dependent variables was used to examine the short-term impact of
      heatwave on preterm birth. A series of cut-off temperatures and durations were
      used to define heatwave. Multivariable analyses were also performed to adjust for
      socio-economic factors, demographic factors, meteorological factors, and ambient
      air pollutants. MAIN OUTCOME MEASURE: Spontaneous preterm births. RESULTS: The
      adjusted hazard ratios (HRs) ranged from 1.13 (95% CI 1.03-1.24) to 2.00 (95% CI
      1.37-2.91) by using different heatwave definitions, after controlling for
      demographic, socio-economic, and meteorological factors, and air pollutants.
      CONCLUSIONS: Heatwave was significantly associated with preterm birth: the
      associations were robust to the definitions of heatwave. The threshold
      temperatures, instead of duration, could be more likely to influence the
      evaluation of birth-related heatwaves. The findings of this study may have
      significant public health implications as climate change progresses.

PMID- 24034564
TI  - Epicardial fat thickness is associated with impaired coronary flow reserve in
      hemodialysis patients.
AB  - Cardiovascular disease (CVD) is the main cause of mortality in hemodialysis (HD)
      patients. Epicardial fat tissue (EFT) is a new risk factor in CVD. The aim of
      this study was to evaluate the association between EFT and coronary artery flow
      reserve (CFR), which is an early indicator of endothelial dysfunction in coronary
      vessels of HD patients. We performed a cross-sectional study including 71 chronic
      HD patients and 65 age- and sex-matched healthy controls. Epicardial fat tissue
      was significantly higher in HD patients when compared to healthy controls (6.53
      +/- 1.01 mm vs. 5.79 +/- 1.06 mm, respectively, P < 0.001). On transthoracic
      Doppler echocardiography, CFR values were significantly lower in HD patients when
      compared to healthy controls (1.73 +/- 0.11 vs. 2.32 +/- 0.28, P < 0.001).
      Correlation analysis showed CFR values to be inversely correlated with EFT (r = 
      0.287, P < 0.05). Multiple linear regression analysis was used to define
      independent determinants of EFT in HD patients. Artery flow reserve, age, body
      mass index and total cholesterol levels were independently correlated with EFT
      thickness. This study demonstrated that EFT was significantly higher among HD
      patients compared to healthy controls. In addition, this study was the first to
      demonstrate an inverse correlation between EFT and CFR in this patient
      population. 

PMID- 24034565
TI  - Maternal phylogenetic relationships and genetic variation among Arabian horse
      populations using whole mitochondrial DNA D-loop sequencing.
AB  - BACKGROUND: Maternal inheritance is an essential point in Arabian horse
      population genetics and strains classification. The mitochondrial DNA (mtDNA)
      sequencing is a highly informative tool to investigate maternal lineages. We
      sequenced the whole mtDNA D-loop of 251 Arabian horses to study the genetic
      diversity and phylogenetic relationships of Arabian populations and to examine
      the traditional strain classification system that depends on maternal family
      lines using native Arabian horses from the Middle East. RESULTS: The variability
      in the upstream region of the D-loop revealed additional differences among the
      haplotypes that had identical sequences in the hypervariable region 1 (HVR1).
      While the American-Arabians showed relatively low diversity, the Syrian
      population was the most variable and contained a very rare and old haplogroup.
      The Middle Eastern horses had major genetic contributions to the Western horses
      and there was no clear pattern of differentiation among all tested populations.
      Our results also showed that several individuals from different strains shared a
      single haplotype, and individuals from a single strain were represented in
      clearly separated haplogroups. CONCLUSIONS: The whole mtDNA D-loop sequence was
      more powerful for analysis of the maternal genetic diversity in the Arabian
      horses than using just the HVR1. Native populations from the Middle East, such as
      Syrians, could be suggested as a hot spot of genetic diversity and may help in
      understanding the evolution history of the Arabian horse breed. Most importantly,
      there was no evidence that the Arabian horse breed has clear subdivisions
      depending on the traditional maternal based strain classification system.

PMID- 24034566
TI  - Vasa nervorum in rat major pelvic ganglion are innervated by nitrergic nerve
      fibers.
AB  - INTRODUCTION: The vasa nervorum comprises a network of small diameter blood
      vessels that provide blood supply to nerves and ganglia. The cell bodies of
      autonomic nerves innervating the urogenital organs are housed in the major pelvic
      ganglia (MPG) in rats. The vasa nervorum of rat MPG have not been characterized
      previously, and it is not known whether these blood vessels are innervated by
      neuronal nitric oxide synthase (nNOS) containing nitrergic nerves. AIM: To
      characterize the blood vessels in and around the rat MPG and to assess their
      nitrergic innervation. MAIN OUTCOME MEASURES: Characterization of small blood
      vessels in and around the rat MPG and expression of nNOS in nerve fibers around
      those blood vessels. METHODS: MPG were obtained from healthy Sprague Dawley rats,
      fixed in paraformaldehyde, frozen and sectioned using a cryostat. The blood
      vessels and their nitrergic innervation were assessed with immunohistochemistry
      using antibodies against alpha-smooth muscle actin (smooth muscle marker), CD31
      (endothelial marker), collagen IV (basal membrane marker) and nNOS. The
      immunofluorescence was imaged using a laser scanning confocal microscope.
      RESULTS: The neuronal cell bodies were contained within a capsule in the MPG.
      Blood vessels were observed within the capsule of the MPG as well as outside the
      capsule. The blood vessels inside the capsule were CD31-positive capillaries with
      no smooth muscle staining. Outside the capsule capillaries, arterioles and
      venules were observed. The extra-capsular arterioles and venules, but not the
      capillaries were innervated by nNOS-positive nerve fibers. CONCLUSIONS: This
      study, to our knowledge, is the first to demonstrate the blood vessel
      distribution pattern and their nitrergic innervation in the rat MPG. While
      similar studies in human pelvic plexus are warranted, these results suggest that
      the blood flow in the MPG may be regulated by nitrergic nerve fibers and reveal a
      reciprocal relationship between nerves and blood vessels.

PMID- 24034567
TI  - Systematic review of saturated fatty acids on inflammation and circulating levels
      of adipokines.
AB  - Diet is one factor that plays a part in coronary heart disease risk through
      multiple biological mechanisms including subclinical inflammation. In this
      review, we aimed to systematically assess and summarize evidence regarding the
      association of saturated fatty acids (SFAs) with inflammatory markers and
      adipokines. An electronic search of the literature was conducted up to September
      2010 using Medline, Scopus, Web of Science, and Science Direct (updated from
      September 2010 to August 2011 through Medline). Original studies that were
      written in Portuguese, English, Spanish, or French, and addressed the effects of
      SFA (not dietary sources or SFA-rich diets) on inflammatory markers or adipokines
      in adult populations were considered eligible. Data from 15 studies providing
      adjusted estimates were extracted. The publication year varied from 1995 to 2010
      and the sample size from 54 to 4900. Most studies were cross sectional, with 3
      studies using a prospective design. Twelve studies assessed total SFA, and 3
      studies considered their subtypes, which were measured through dietary
      assessments (11 studies) or in blood samples (4 studies). Significant positive
      associations were observed between SFA and soluble intercellular adhesion
      molecule-1 and interleukin-6, whereas no significant associations were observed
      with E-selectin, tumor necrosis factor alpha, granulocyte-macrophage colony
      stimulating factor, fibrinogen, and adiponectin. For high-sensitivity C-reactive
      protein, 2 studies showed significant positive associations, whereas 3 studies
      reported no significant associations. One study reported a significant inverse
      association of SFA with leptin, although the other 3 found no significant
      associations. Based on this systematic review, a potential positive association
      of SFA with high-sensitivity C-reactive protein but not with adipokines is
      suggested, which should be confirmed by future research. 

PMID- 24034568
TI  - Comparison and validation of 2 analytical methods for measurement of urinary
      sucrose and fructose excretion.
AB  - Urinary sugars excretion has been proposed as a potential biomarker for intake of
      sugars. In this study, we compared 2 analytical methods (gas chromatography [GC]
      and enzymatic reactions-UV absorption) for quantifying urinary fructose and
      sucrose using 24-hour urine samples from a randomized crossover controlled
      feeding study. All samples were successfully quantified by the GC method;
      however, 21% and 1.9% of samples were below the detection limit of the enzymatic
      method for sucrose and fructose, respectively. Although the correlation between
      the 2 methods was good for fructose (Pearson correlation, 0.71), the correlation
      was weak for sucrose (Pearson correlation, 0.27). We favor the GC method because
      of its better sensitivity, simplicity, and the ability to quantify fructose and
      sucrose directly in the same run. Of the 106 samples from 53 participants with
      complete urine collection after 2 study diets, 24-hour urinary fructose excretion
      was significantly associated with fructose intake. The sum of 24-hour urinary
      fructose and sucrose was significantly associated with total sugars consumption.
      However, variation in intakes of sugars explained only a modest amount of
      variation in urinary sugars excretion. In the unadjusted models, fructose intake
      explained 24.3% of urinary fructose excretion, and intake of total sugars
      explained 16.3% of the sum of urinary fructose and sucrose. The adjusted models
      explained 44.3% of urinary fructose excretion and 41.7% of the sum of urinary
      fructose and sucrose. Therefore, we caution using these biomarkers to predict
      sugars consumption before other factors that determine urinary sugars excretion
      are understood. 

PMID- 24034569
TI  - A beverage of Asiatic plantain extracts alleviated postprandial oxidative stress
      in overweight hyperlipidemic subjects challenged with a high-fat meal: a
      preliminary study.
AB  - There is emerging interest in the potential of the phenolic compounds of Asiatic
      plantain (Plantago asiatica L.) to attenuate in vitro and in vivo oxidative
      stress. We hypothesized that a single administration of Asiatic plantain beverage
      may exert protective effects against postprandial oxidative stress. This
      preliminary study was designed to compare the ability of different doses of
      Asiatic plantain beverage to mitigate the postprandial effects of a high-fat meal
      on the oxidation of lipids and DNA in overweight hyperlipidemic subjects. In a
      randomized, double-blind, placebo-controlled parallel design (n = 10/group), 40
      subjects were administered a single high-fat meal with either a placebo or 1 of 3
      Asiatic plantain extract beverages (low, intermediate, or high dose). Blood
      samples were obtained at fasting and 60, 120, 240, and 360 minutes (total of 5
      samples) after intervention. The data showed a tendency for plasma free fatty
      acid levels to decrease in response to high-dose Asiatic plantain at all time
      points. Plasma oxidized low-density lipoprotein levels were significantly reduced
      with high-dose Asiatic plantain at 120 minutes (P = .0251 vs placebo). A comet
      assay revealed that DNA damage in lymphocytes was significantly decreased by
      Asiatic plantain at 360 minutes (P = .0225 vs placebo). There were no treatment
      differences in triglyceride or malondialdehyde levels. The maximum suppression
      was achieved with a high dose (20 g Asiatic plantain extract/80 mL). These
      results suggest that by protecting low-density lipoprotein and DNA, an Asiatic
      plantain beverage may be useful to enhance antioxidant. 

PMID- 24034570
TI  - Ingestion of thermally oxidized sunflower oil decreases postprandial lipemia
      mainly in younger individuals.
AB  - Animal studies have shown that diets rich in thermally oxidized fat increase
      glucose and decrease insulin and triglyceride (TG) concentrations in the blood.
      We hypothesized that ingestion of a potato meal rich in thermally oxidized
      sunflower oil (TOSO) would decrease postprandial concentrations of insulin,
      incretins, and TG and increase plasma glucose concentrations. Twenty healthy
      subjects aged 22 to 70 years consumed meals rich in TOSO or unheated sunflower
      oil and containing paracetamol (1.5 g) in a randomized, crossover trial. Blood
      samples were taken at baseline and 10, 20, 30, 60, 90, and 120 minutes after the
      meals and glucose, insulin, TG, nonesterified fatty acids, glucagon-like
      polypeptide-1, glucose-independent polypeptide, and paracetamol (as a marker of
      gastric emptying) were measured in plasma or serum. The incremental areas under
      the curve of glucose, insulin, nonesterified fatty acid, incretins, and
      paracetamol levels were not significantly different between the meals. Plasma TG
      incremental area under the curve was 44% lower after the TOSO meal at a marginal
      level of significance (P = .06) in the total study population and was
      significantly (P = .04) and 61% lower in those of median age and younger (n =
      11). These data suggest that ingestion of TOSO may acutely decrease plasma TG
      mainly in younger individuals and does not acutely affect glucose and insulin
      metabolism or gastric emptying in healthy subjects. 

PMID- 24034571
TI  - Higher glycemic index and glycemic load diet is associated with increased risk of
      esophageal squamous cell carcinoma: a case-control study.
AB  - Several studies have indicated the association between intake of foods high in
      dietary glycemic index (GI) and glycemic load (GL) with an increased risk of
      digestive tract cancers. We hypothesized that GI and GL may be associated with
      risk of esophageal squamous cell carcinoma (ESCC) in a high-risk population in
      Iran. In total, we interviewed 47 cases with incident of ESCC and 96 frequency
      matched hospital controls, then calculated the average dietary GI and GL via a
      validated food frequency questionnaire. Dietary GL was calculated as a function
      of GI, carbohydrate content, and frequency of intake of certain foods. Dietary GI
      and GL levels were significantly higher among the ESCC cases compared with the
      controls (P < .05). After adjustment for potential confounders, those in the
      highest tertile of dietary GI had 2.95 times higher risk of ESCC compared with
      those in the lowest (95% confidence interval, 1.68-3.35; P for trend = .002). In
      addition, being in the highest tertile of dietary GL was positively associated
      with an ESCC risk (odds ratio, 3.49; 95% confidence interval, 2.98-4.41; P for
      trend = .001). Findings of the present study indicate that diets with high GI and
      GL might have potentially unfavorable effects on ESCC risk and suggest a possible
      role for excess circulating insulin and related insulin-like growth factor 1 in
      esophageal cancer development. 

PMID- 24034572
TI  - Caffeine intake reduces sleep duration in adolescents.
AB  - In our study, we hypothesized that higher caffeine intake would be associated
      with lower sleep duration among 13-year-old adolescents. In addition, we aimed to
      identify food sources of caffeine intake in this sample. Eligible participants
      were adolescents who were born in 1990 and attended school in Porto, Portugal, in
      2003/2004. Self-administered questionnaires were used, and diet was evaluated
      using a food frequency questionnaire. From the 2160 eligible participants, only
      1522 with valid information regarding their diet were included in this study. In
      our sample, the median intake of caffeine was 23.1 mg/d, with soft drinks being
      the major source. Ice tea presented the highest median (25th-75th percentiles)
      contribution (33.1% [14.0-52.1]), followed by cola (21.1% [6.4-37.6]). Regarding
      cocoa products, chocolate bars presented a median contribution of 5.1% (1.0
      14.0), and snacks containing chocolate had a contribution of 3.0% (0.5-7.2).
      Coffee and tea presented a negligible contribution. Adolescents who reported less
      sleep duration and those who spent more time watching TV during the weekend had a
      significantly higher caffeine intake. Overall, boys had higher intakes of
      caffeine from soft drinks, and private school attendees, those who had parents
      with more education, who reported less television viewing time and had lower body
      mass index presented higher intakes of caffeine from chocolate. Considering
      sleeping more than 9.5 hours as a reference class, for each increase of 10 mg/d
      in caffeine intake, we found that the odds ratio of sleeping 8.5 hours or less
      was 1.12 (95% confidence interval, 1.06-1.19). Our results support the hypothesis
      that caffeine intake was inversely associated with sleep duration in adolescents.

PMID- 24034573
TI  - Genetic ablation of carotene oxygenases and consumption of lycopene or tomato
      powder diets modulate carotenoid and lipid metabolism in mice.
AB  - Carotene-15,15'-monooxygenase (CMO-I) cleaves beta-carotene to form vitamin A,
      whereas carotene-9',10'-monooxygenase (CMO-II) preferentially cleaves non
      provitamin A carotenoids. Recent reports indicate that beta-carotene metabolites
      regulate dietary lipid uptake, whereas lycopene regulates peroxisome proliferator
      activated receptor expression. To determine the physiologic consequences of
      carotenoids and their interactions with CMO-I and CMO-II, we characterized
      mammalian carotenoid metabolism, metabolic perturbations, and lipid metabolism in
      female CMO-I(-/-) and CMO-II(-/-) mice fed lycopene or tomato-containing diets
      for 30 days. We hypothesized that there would be significant interactions between
      diet and genotype on carotenoid accumulation and lipid parameters. CMO-I(-/-)
      mice had higher levels of leptin, insulin, and hepatic lipidosis but lower levels
      of serum cholesterol. CMO-II(-/-) mice had increased tissue lycopene and
      phytofluene accumulation, reduced insulin-like growth factor 1 levels and
      cholesterol levels, but elevated liver lipids and cholesterol compared with wild
      type mice. The diets did not modulate these genotypic perturbations, but lycopene
      and tomato powder significantly decreased serum insulin-like growth factor 1.
      Tomato powder also increased hepatic peroxisome proliferator-activated receptor
      expression, independent of genotype. These data point to the pleiotropic actions
      of CMO-I and CMO-II supporting a strong role of these proteins in regulating
      tissue carotenoid accumulation and the lipid metabolic phenotype as well as
      tomato carotenoid-independent regulation of lipid metabolism. 

PMID- 24034574
TI  - Enzymatically synthesized glycogen reduces lipid accumulation in diet-induced
      obese rats.
AB  - Based on a recent study indicating that enzymatically synthesized glycogen (ESG)
      possesses a dietary, fiber-like action, we hypothesized that ESG can reduce the
      risk of obesity. In this study, the antiobesity effects of ESG were investigated
      in a model of diet-induced obesity. Male Sprague-Dawley rats were divided into 4
      groups and fed a normal or high-fat diet, with or without 20% ESG, for 4 weeks.
      Body weight, food intake, lipid deposition in the white adipose tissues and
      liver, fecal lipid excretion, and plasma lipid profiles were measured. At week 3,
      the body fat mass was measured using an x-ray computed tomography system, which
      showed that ESG significantly suppressed the high-fat diet-induced lipid
      accumulation. Similar results were observed in the weight of the adipose tissue
      after the experiment. Moreover, ESG significantly suppressed the lipid
      accumulation in the liver but increased fecal lipid excretion. The plasma
      concentrations of triacylglycerol and nonesterified fatty acid were lowered after
      a high-fat diet, whereas the total bile acid concentration was increased by ESG.
      However, the hepatic messenger RNA (mRNA) levels of enzymes related to lipid
      metabolism were not affected by ESG. Conversely, the mRNA levels of long-chain
      acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase were up-regulated
      by ESG in the muscle. These results suggest that the combined effects of
      increased fecal lipid excretion, increased mRNA levels of enzymes that oxidize
      fatty acids in the muscle, and increased total bile acid concentration in the
      plasma mediate the inhibitory effect of ESG on lipid accumulation. 

PMID- 24034575
TI  - Panax ginseng exerts antiproliferative effects on rat hepatocarcinogenesis.
AB  - It has been proposed that ginseng has chemopreventive effects against several
      types of cancer in animals and humans. However, the mechanisms underlying the
      chemopreventive activities of fresh ginseng against hepatocarcinogenesis have not
      yet been elucidated. Therefore, we hypothesized that these ginseng species may
      prevent hepatocarcinogenesis but that the chemopreventive mechanisms may differ
      by species. To determine the chemopreventive and therapeutic potential of 3
      different types of fresh ginseng on hepatocarcinogenesis, Sprague-Dawley rats
      were injected with diethylnitrosamine and fed diets containing 2% Panax japonicus
      CA Meyer (JN), P. quinquefolius L (QQ), or P. ginseng CA Meyer (GS) for 10 weeks.
      Glutathione S-transferase P form (GST-P)-positive foci, a stable marker for rat
      hepatocarcinogenesis, were shown in all carcinogen-injected rats; but only the GS
      diet significantly reduced the area and number (62% and 68%, respectively; P <
      .05) of GST-P-positive foci compared with the diethylnitrosamine control group.
      In addition, the number of proliferating cell nuclear antigen-positive
      hepatocytes in the GST-P-positive area was significantly decreased in the GS
      group but not in the JN or QQ groups. Using cDNA microarray analyses to
      investigate the underlying molecular mechanisms, we observed that the p53
      signaling pathway was altered by the GS diet and that the expression of Cyclin
      D1, Cyclin G1, Cdc2a, and Igf-1, which are involved in the p53 signaling pathway,
      was downregulated by the GS diet. Our data demonstrate, for the first time, that
      GS, but not JN or QQ, induces cell cycle arrest in hepatocarcinogenesis. This
      study suggests that fresh GS has potential chemopreventive effects and may prove
      to be a therapeutic agent against hepatocarcinogenesis. 

PMID- 24034576
TI  - Attenuation of the activated mammalian target of rapamycin pathway might be
      associated with renal function reserve by a low-protein diet in the rat remnant
      kidney model.
AB  - The mammalian target of rapamycin (mTOR), a regulator of cellular protein
      synthesis and cell growth, plays an important role in the progression of renal
      hypertrophy and renal dysfunction in experimental chronic kidney disease models.
      Because the mTOR activity is regulated by nutrients including amino acids, we
      tested the hypothesis that the renoprotective effect of a low-protein diet (LPD)
      might be associated with the attenuation of the renal mTOR pathway. In this
      study, 5/6 nephrectomized rats were fed an LPD or a normal protein diet (NPD),
      and a number of rats that were fed an NPD received rapamycin (1.0 mg kg-1 d-1), a
      specific inhibitor of mTOR. After 6 weeks, renal tissue was collected to evaluate
      the activity of the mTOR pathway and histologic changes. The phosphorylation of
      p70S6k, a kinase in the downstream of mTOR, was significantly higher in the NPD
      fed rats that showed progressive renal dysfunction than in the sham-operated rats
      (NPD). The LPD attenuated the excessive phosphorylation of p70S6k concomitant
      with reduced proteinuria and improved renal histologic changes in the 5/6
      nephrectomized rats. The effects of the LPD were similar to the effects of
      rapamycin. The expression of phosphorylated p70S6k was significantly correlated
      with proteinuria (r2 = 0.63, P < .001), the glomerular area (r2 = 0.60, P <
      .001), and the number of phosphorylated Smad2-positive cells in the glomerulus
      (r2 = 0.26, P < .05) of these rats. These results suggest that the preventive
      effect of an LPD on the progression of renal failure is associated with
      attenuation of the activated mTOR/p70S6k pathway in the rat remnant kidney model.

PMID- 24034577
TI  - Supplementation with n-3 polyunsaturated fatty acids to lipopolysaccharide
      induced rats improved inflammation and functional properties of renal Na,K
      ATPase.
AB  - Measurements of enzyme kinetics of renal Na, K-ATPase were used for
      characterization of ATP- and Na+-binding sites in rats that were subjected to 10
      days of moderate inflammation that was induced by a single dose of Escherichia
      coli lipopolysaccharides (LPSs) at a dose of 1 mg kg-1 body weight. We
      hypothesized that LPSs might initiate a malfunction of renal Na, K-ATPase, which
      is a key enzyme involved in regulation of sodium homeostasis in the organism. We
      also investigated the potential effect that fish oil (FO) has in the prevention
      of Na, K-ATPase alterations by administering FO daily at a dose of 30 mg kg-1.
      Alone, LPS elevated the level of C-reactive protein by more than 500% and free
      radicals by 36% in plasma, as indicated by an increased level of malondialdehyde.
      The Na, K-ATPase was slightly altered in the vicinity of the ATP-binding site as
      suggested by the 9% increase of the concentration of ATP necessary for half
      maximal activation of the enzyme, thus indicating a deteriorated binding of ATP
      as a consequence of inflammation. Daily supplementation of FO partly attenuated
      LPS-induced injury, as observed by a significant decrease in the plasma levels of
      C-reactive protein and free radicals, hence maintaining the activity of renal Na,
      K-ATPase to the level of healthy control animals. In conclusion, our findings
      showed that FO prevented an excessive malondialdehyde production in LPS-treated
      animals and stabilized renal Na, K-ATPase.

PMID- 24034578
TI  - Addressing a critique of the TEASI framework for invasive species risk
      assessment.
AB  - We address criticism that the Transport, Establishment, Abundance, Spread, Impact
      (TEASI) framework does not facilitate objective mapping of risk assessment
      methods nor defines best practice. We explain why TEASI is appropriate for
      mapping, despite inherent challenges, and how TEASI offers considerations for
      best practices, rather than suggesting one best practice. 

PMID- 24034579
TI  - Manipulation of colony environment modulates honey bee aggression and brain gene
      expression.
AB  - The social environment plays an essential role in shaping behavior for most
      animals. Social effects on behavior are often linked to changes in brain gene
      expression. In the honey bee (Apis mellifera L.), social modulation of individual
      aggression allows colonies to adjust the intensity with which they defend their
      hive in response to predation threat. Previous research has showed social effects
      on both aggression and aggression-related brain gene expression in honey bees,
      caused by alarm pheromone and unknown factors related to colony genotype. For
      example, some bees from less aggressive genetic stock reared in colonies with
      genetic predispositions toward increased aggression show both increased
      aggression and more aggressive-like brain gene expression profiles. We tested the
      hypothesis that exposure to a colony environment influenced by high levels of
      predation threat results in increased aggression and aggressive-like gene
      expression patterns in individual bees. We assessed gene expression using four
      marker genes. Experimentally induced predation threats modified behavior, but the
      effect was opposite of our predictions: disturbed colonies showed decreased
      aggression. Disturbed colonies also decreased foraging activity, suggesting that
      they did not habituate to threats; other explanations for this finding are
      discussed. Bees in disturbed colonies also showed changes in brain gene
      expression, some of which paralleled behavioral findings. These results show that
      bee aggression and associated molecular processes are subject to complex social
      influences. 

PMID- 24034580
TI  - Self-administration of misoprostol prior to intrauterine device insertion among
      nulliparous women: a randomized controlled trial.
AB  - BACKGROUND: Barriers to intrauterine device (IUD) use in nulliparous women
      include fear of pain with insertion and provider perception of difficulty with
      insertion. The goal of this study was to evaluate whether misoprostol prior to
      IUD insertion in nulliparous women eased insertion and decreased pain. STUDY
      DESIGN: This was a double-blinded, randomized, controlled trial. Nulliparous
      women requesting an IUD were randomized to buccal placement of 400-mcg
      misoprostol or placebo. Provider ease of insertion and patient-reported pain were
      measured using a 100-mm visual analogue scale. RESULTS: Seventy-three subjects
      completed the study. Baseline characteristics were similar between groups.
      Provider perception of ease of insertion was not different between study and
      control groups (28.97 mm, 22.33 mm, p=.18). Pain immediately prior to IUD
      insertion (10.84 vs. 2.11; p=.003) and after IUD insertion (46.50 vs. 35.14;
      p=.040) was higher for those in the study group compared to the control group.
      CONCLUSION: This study demonstrates that it is not helpful to provide misoprostol
      for cervical ripening prior to insertion of IUDs as it does not improve ease of
      insertion for provider or decrease reported pain for the woman, and it may
      increase women's pain experience with insertion. IMPLICATION STATEMENT: Our study
      demonstrates that providers do not perceive nulliparous IUD insertion as
      difficult; women do experience pain with insertion but find the experience
      acceptable. The addition of misoprostol for cervical ripening prior to insertion
      does not ease insertion for providers and increases the pain level experienced by
      women.

PMID- 24034581
TI  - Feasibility, effectiveness and safety of transvaginal digoxin administration
      prior to dilation and evacuation.
AB  - OBJECTIVES: This study evaluates the feasibility, efficacy and safety of
      transvaginal digoxin administration to induce fetal demise prior to dilation and
      evacuation. STUDY DESIGN: This descriptive report from a single center involves a
      large case series of dilations and evacuations (D&Es) ranging from 18 to 22 weeks
      of gestation. Transvaginal feticidal injection with digoxin was attempted in 1640
      cases; intrafetal, intraamniotic and combined (intrafetal and intraamniotic)
      injections were administered. Digoxin dosage ranged from 0.5 to 3.0 mg, with the
      majority receiving 1.0 mg. Cases were reviewed to determine feasibility, efficacy
      and adverse events. RESULTS: Successful completion of transvaginal injection
      occurred in 98.5% (1637/1662) of eligible cases, and 1596 cases were evaluable
      for fetal demise. Demise occurred by the time of D&E in 99.4% of all cases; 99.7%
      of intrafetal injections resulted in fetal demise. Doses >=1 mg were equally
      effective (98.1%-99.6%) regardless of injection site (intraamniotic, combined
      intrafetal/intraamniotic or intrafetal). Doses <1.0 mg were less successful at
      inducing demise if not administered intrafetally (p<.001). Rates of ruptured
      membranes (4.1%), chorioamnionitis (0.49%) and extramural deliveries (0.12%) were
      low. Patients who experienced complications were more likely to be of greater
      gestational age and have had a previous cesarean section. CONCLUSIONS:
      Transvaginal digoxin administration is feasible, effective and safe. IMPLICATION
      STATEMENT: This study demonstrates the feasibility, effectiveness and safety of
      transvaginal digoxin administration in a large clinical cohort. Future studies
      will be needed to determine if this method of administration improves patient
      satisfaction and outcomes when compared to transabdominal feticidal injections.

PMID- 24034582
TI  - Umbilical cord transection to induce fetal demise prior to second-trimester D&E
      abortion.
AB  - OBJECTIVE: Induction of fetal demise via transabdominal injection has been used
      to facilitate second-trimester abortion but requires a second procedure and has
      associated risks. The method of amniotomy, cord transection and documentation of
      fetal asystole immediately prior to dilation and evacuation (D&E) is an
      alternative approach; however, characteristics of this method have not been
      described. STUDY DESIGN: This descriptive report from a single center involves a
      large case series of D&Es ranging from 16 to 23 weeks of gestation. Umbilical
      cord transection (UCT) was attempted immediately prior to D&E in 407 cases, which
      were reviewed to determine success, time to fetal asystole and complications.
      RESULTS: Both UCT and asystole were achieved in 100% of cases. Mean time from UCT
      to asystole was 3.35+/-2.11 min. When compared to cases performed at less than 20
      weeks of gestation, mean time to asystole was slightly longer in the >=20-week
      group (3.7+/-2.4 min vs. 3.1+/-1.9 min; p=.008). Few patients had minor (4.6%) or
      major (0.3%) complications; time to asystole was not associated with
      complications. CONCLUSIONS: Umbilical cord transection immediately prior to D&E
      is a feasible, efficacious and safe way to induce fetal demise without performing
      additional procedures. IMPLICATION STATEMENT: This study demonstrates the
      feasibility, effectiveness and safety of utilizing umbilical cord transection to
      induce fetal demise in a large cohort. This method is an alternative to other
      feticidal procedures.

PMID- 24034583
TI  - Saturated fatty acids alter the late secretory pathway by modulating membrane
      properties.
AB  - Saturated fatty acids (SFA) have been reported to alter organelle integrity and
      function in many cell types, including muscle and pancreatic beta-cells,
      adipocytes, hepatocytes and cardiomyocytes. SFA accumulation results in increased
      amounts of ceramides/sphingolipids and saturated phospholipids (PL). In this
      study, using a yeast-based model that recapitulates most of the trademarks of SFA
      induced lipotoxicity in mammalian cells, we demonstrate that these lipid species
      act at different levels of the secretory pathway. Ceramides mostly appear to
      modulate the induction of the unfolded protein response and the transcription of
      nutrient transporters destined to the cell surface. On the other hand, saturated
      PL, by altering membrane properties, directly impact vesicular budding at later
      steps in the secretory pathway, i.e. at the trans-Golgi Network level. They
      appear to do so by increasing lipid order within intracellular membranes which,
      in turn, alters the recruitment of loose lipid packing-sensing proteins, required
      for optimal budding, to nascent vesicles. We propose that this latter general
      mechanism could account for the well-documented deleterious impacts of fatty
      acids on the last steps of the secretory pathway in several cell types. 

PMID- 24034584
TI  - Inadequate status of iodine nutrition among pregnant women residing in three
      districts of Niamey, the Niger Republic's capital.
AB  - Universal dietary salt iodisation (UDSI) programme was implemented in Niger in
      1996. However, since 2000, there has been a slowdown in progress against iodine
      deficiency. The aim of our study was to assess the iodine status among pregnant
      women in a context where national controls are not effective at ensuring
      universal availability of adequately iodised salt. This is mainly to assess the
      impact of the slowdown in the fight against iodine deficiency in this vulnerable
      group. The study was centred on 240 healthy pregnant women volunteers recruited
      in three districts primary health centres. A control group of 60 non-pregnant,
      non-lactating healthy women was also studied and compared. Median urinary iodine
      concentration (UIC) of all pregnant women was 119 MUg L(-1) , and 61.67% had UIC
      below 150 MUg L(-1) . Median UIC for the first, second and third trimester were
      144, 108 and 92 MUg L(-1) , respectively. The percentage of pregnant women with
      UIC below 150 MUg L(-1) increased from 52% in the first trimester to 66% in the
      third trimester. The median UIC of the control group was 166 MUg L(-1) , and
      28.33% had UIC below 100 MUg L(-1) . No significant relationship was found
      between nutritional iodine status and provenance, age and parity. However,
      significant relationship was found between iodine status and stage of pregnancy,
      gestational age and educational level (P < 0.05). Iodine nutrition status thus
      observed was inadequate in 61.67% of all the pregnant women. It is therefore
      urgent to revitalise implementation of the UDSI programme, and in the short term
      to consider iodine supplementation for pregnant women.

PMID- 24034585
TI  - Risk of lymph node metastasis in malignant colorectal polyps.

PMID- 24034586
TI  - Dog obesity--the need for identifying predisposing genetic markers.
AB  - Incidence of overweight and obesity in dogs exceeds 30%, and several breeds are
      predisposed to this heritable phenotype. Rapid progress of canine genomics and
      advanced knowledge on the genetic background of human obesity bring a unique
      opportunity to perform such studies in dogs. Natural candidate genes for obesity
      are these encoding adipokines. Extended studies in humans indicated that
      polymorphisms of three of them, i.e. ADIPOQ, IL1 and TNF, are associated with
      predisposition to obesity. On the other hand, the use of genome-wide association
      studies revealed an association between human obesity and polymorphism of more
      than 50 other genes. Until now only few preliminary reports on polymorphism of
      canine FTO, MC4R, MC3R and PPARG genes have been published. Since the dog is a
      valuable model organism for human diseases one can foresee that such studies may
      also contribute to an in-depth understanding of human obesity pathogenesis. 

PMID- 24034587
TI  - Introduction: Focus on mitochondria.
AB  - This is a series of papers (three reviews and five regular papers) focused on
      Mitochondria from authors contributing to two FEBS courses on Mitochondria held
      in 2012. These papers focus on: (i) mitochondrial biogenesis (regulation by
      phosphorylation, import of SOD1 and Mia40, mitophagy and tRNA variants) or (ii)
      mitochondrial pathology (ischaemia, obesity and Parkinson's disease). 

PMID- 24034589
TI  - Recent advances in knee surgery.

PMID- 24034588
TI  - Rotavirus genotypes associated with childhood severe acute diarrhoea in southern
      Ghana: a cross-sectional study.
AB  - BACKGROUND: Rotavirus immunization has been effective in developed countries
      where genotype G1P[8] is the predominant rotavirus strain. Knowledge of
      circulating strains in a population before introduction of rotavirus immunization
      program will be useful in evaluating the effect of the intervention. METHODS:
      Rotavirus was identified by enzyme immuno-assay (EIA) on stool specimens of
      children (age 0-59 months) hospitalized with acute gastroenteritis from August
      2007 to February 2011 in Accra, Ghana. Rotavirus positive specimens were further
      characterized by polyacrylamide gel electrophoresis (PAGE) and reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: Of the 2277 acute
      gastroenteritis hospitalizations 1099 (48.2%) were rotavirus-positive by EIA. Of
      the 1099 cases 977 (89%) were PAGE positive. All EIA positive specimens were
      further subjected to RT-PCR and 876 (79.7%) had sufficient material for
      characterization. Of these 876 cases, 741 (84.6%) were assigned G genotype, 709
      (80.9%) P genotype, and 624 (71.2%) both G and P genotypes. We identified 8 G
      genotypes (G1, G2, G3, G4, G8, G9, G10, G12) and 3 P genotypes (P[4], P[6],
      P[8]). G1 (50.9%), G2 (18.8%), G3 (12.8%), P[8] (36.1%) and P[6] (30.7%) were the
      most prevalent. The most prevalent genotype combination was G1P[8] (28%). Mixed G
      (7.3%) and P (24.2%) genotypes were not uncommon. There was year-by-year and
      seasonal variations for most genotypes. CONCLUSION: There is great diversity of
      rotavirus strains in children with severe gastroenteritis in southern Ghana. Even
      though cross-protection with vaccine-induced immunity occurs, continued strain
      surveillance is recommended after the introduction of rotavirus vaccine in the
      national immunization program.

PMID- 24034590
TI  - Uncertainties surrounding the choice of surgical treatment for 'bone on bone'
      medial compartment osteoarthritis of the knee.
AB  - A number of different surgical interventions can be used for treating antero
      medial osteoarthritis (AMOA) of the knee and this choice can present challenges
      for patient's decision-making. Patients with AMOA can undergo Total Knee
      Replacement (TKR), Unicompartmental Knee Replacement (UKR) or High Tibial
      Osteotomy (HTO) for the same pathology. However many uncertainties still exist as
      to deciding which operation is best for individual patients and the Orthopaedic
      community has failed to systematically compare treatment options. The relative
      lack of scientifically based evidence has impacted on the ability to provide
      clear guidelines on treatment choice, patient suitability and direct patient
      preference for treatment. This paper, using available evidence, discusses the
      issue and offers some suggestions for future development. 

PMID- 24034591
TI  - Can technology improve alignment during knee arthroplasty.
AB  - Component malalignment remains a concern in total knee arthroplasty (TKA);
      therefore, a series of technologies have been developed to improve alignment. The
      authors conducted a systematic review to compare computer-assisted navigation
      with conventional instrumentation, and assess the current evidence for patient
      matched instrumentation and robot-assisted implantation. An extensive search of
      the PubMed database for relevant meta-analyses, systematic reviews and original
      articles was performed, with each study scrutinised by two reviewers. Data on
      study characteristics and outcomes were extracted from each study and compared.
      In total 30 studies were included: 10 meta-analyses comparing computer-assisted
      navigation and conventional instrumentation, 13 studies examining patient-matched
      instrumentation, and seven investigating robot-assisted implantation. Computer
      assisted navigation showed significant and reproducible improvements in
      mechanical alignment over conventional instrumentation. Patient-matched
      instrumentation appeared to achieve a high degree of mechanical alignment,
      although the majority of studies were of poor quality. The data for robot
      assisted surgery was less indicative. Computer-assisted navigation improves
      alignment during TKA over conventional instrumentation. For patient-matched
      instrumentation and robot-assisted implantation, alignment benefits have not been
      reliably demonstrated. For all three technologies, clinical benefits cannot
      currently be assumed, and further studies are required. Although current
      technologies to improve alignment during TKA appear to result in intra-operative
      benefits, their clinical impact remains unclear, and surgeons should take this
      into account when considering their adoption.

PMID- 24034592
TI  - Fast-track knee arthroplasty -- status and future challenges.
AB  - BACKGROUND: Fast-track programs have been developed for different surgical
      procedures leading to higher patient satisfaction and lower morbidity. This
      concept has been extended to knee arthroplasty in recent years. The purpose of
      this narrative review was to discuss the different aspects of fast-track knee
      arthroplasty. METHOD: Both authors searched the contemporary literature on
      minimally invasive knee arthroplasty and review articles on fast-track surgery
      aiming to summarize recent developments. RESULTS: Length of stay after knee
      arthroplasty is influenced by preoperative risk factors, anaesthetic and surgical
      techniques, pain, orthostatic intolerance, cognitive function, sleep
      disturbances, bleeding and anaemia and finally muscle function and
      rehabilitation. CONCLUSIONS: Fast-track surgery reduces the length of stay and
      the morbidity after knee arthroplasty. CLINICAL RELEVANCE: Optimisation of pre-,
      per- and postoperative pathway for knee arthroplasty reduces morbidity after this
      type of surgery and results in shorter length of stay.

PMID- 24034593
TI  - The contemporary management of anterior knee pain and patellofemoral instability.
AB  - In this review the evidence for the management of patients with patellofemoral
      disorders is presented confined to anterior knee pain and patellar dislocation
      (excluding patellofemoral arthritis). Patients present along a spectrum of these
      two problems and are best managed with both problems considered. The key to
      managing these patients is by improving muscle function, the patient losing
      weight (if overweight), and judicious use of analgesics if pain is an important
      feature. Hypermobility syndrome should always be looked for since this is a
      prognostic indicator for a poor operative outcome. Operations should be reserved
      for those with correctable anatomical abnormalities that have failed conservative
      therapy. The current dominant operation is a medial patellofemoral ligament
      reconstruction. 

PMID- 24034594
TI  - Unusually high impact of influenza B during the early 2012-2013 influenza season
      in Wales--epidemiology and clinical analysis of the first 100 cases.
AB  - BACKGROUND: Influenza B is often regarded as the milder form of the disease. The
      early 2012-2013 season in Wales saw the highest rate of influenza B-associated
      primary care consultations since 1994-1995 and considerable hospitalisations.
      OBJECTIVES: This report summarises features of the first 100 confirmed cases
      during 2012-2013 in Wales. METHODS: Case information was sourced from routine
      laboratory testing and virological surveillance. RESULTS AND CONCLUSIONS:
      Influenza B (Yamagata lineage) viruses dominated, mainly affecting younger
      adults, admission to critical care was unexpectedly common. Low vaccine uptake
      amongst at-risk patients may have contributed to the burden of influenza in
      secondary care in Wales.

PMID- 24034595
TI  - Eating a healthy lunch improves serum alanine aminotransferase activity.
AB  - BACKGROUND: Nutritional guidance and diet control play important roles in the
      treatment of obesity and non-alcoholic fatty liver. However, in Japan,
      nutritional guidance is difficult to provide in practice. Therefore, we evaluated
      the effects of providing the 'once-a-day' intervention of a healthy lunch on
      various metabolic parameters. METHODS: For a 1-month preparatory period, 10
      subjects generally consumed the lunches that were provided by the worksite
      cafeteria. This was followed by a 1-week washout period, after which, the
      subjects consumed healthy, low-calorie, well-balanced lunches for a 1-month test
      period. After the preparatory and test periods, blood samples were obtained from
      all subjects. The serum levels of indices relevant to metabolic syndrome and
      fatty liver were measured. RESULTS: Serum alanine aminotransferase activity
      significantly decreased by 20.3% after the healthy intervention. However, the
      indices of metabolic syndrome did not significantly change. Analysis of the
      relationship between serum alanine aminotransferase activity and nutrient content
      indicated that the improvement of serum alanine aminotransferase status was due
      to the higher vegetable content and lower animal-source protein of the meals
      provided. CONCLUSIONS: In summary, the 'once-a-day' intervention of providing a
      healthy lunch improved serum alanine aminotransferase status. A diet high in
      vegetables and low in animal-based protein is important in maintaining a healthy
      condition.

PMID- 24034596
TI  - Detection of doublecortin domain-containing 2 (DCDC2), a new candidate tumor
      suppressor gene of hepatocellular carcinoma, by triple combination array
      analysis.
AB  - BACKGROUND: To detect genes correlated with hepatocellular carcinoma (HCC), we
      developed a triple combination array consisting of methylation array, gene
      expression array and single nucleotide polymorphism (SNP) array analysis.
      METHODS: A surgical specimen obtained from a 68-year-old female HCC patient was
      analyzed by triple combination array, which identified doublecortin domain
      containing 2 (DCDC2) as a candidate tumor suppressor gene of HCC. Subsequently,
      samples from 48 HCC patients were evaluated for their DCDC2 methylation and
      expression status using methylation specific PCR (MSP) and semi-quantitative
      reverse transcriptase (RT) PCR, respectively. Then, we investigated the
      relationship between clinicopathological factors and methylation status of DCDC2.
      RESULTS: DCDC2 was revealed to be hypermethylated (methylation value 0.846, range
      0-1.0) in cancer tissue, compared with adjacent normal tissue (0.212) by
      methylation array in the 68-year-old female patient. Expression array showed
      decreased expression of DCDC2 in cancerous tissue. SNP array showed that the copy
      number of chromosome 6p22.1, in which DCDC2 resides, was normal. MSP revealed
      hypermethylation of the promoter region of DCDC2 in 41 of the tumor samples.
      DCDC2 expression was significantly decreased in the cases with methylation (P =
      0.048). Furthermore, the methylated cases revealed worse prognosis for overall
      survival than unmethylated cases (P = 0.048). CONCLUSIONS: The present study
      indicates that triple combination array is an effective method to detect novel
      genes related to HCC. We propose that DCDC2 is a tumor suppressor gene of HCC.

PMID- 24034597
TI  - Interplay between human microglia and neural stem/progenitor cells in an
      allogeneic co-culture model.
AB  - Experimental neural cell therapies, including donor neural stem/progenitor cells
      (NPCs) have been reported to offer beneficial effects on the recovery after an
      injury and to counteract inflammatory and degenerative processes in the central
      nervous system (CNS). The interplay between donor neural cells and the host CNS
      still to a large degree remains unclear, in particular in human allogeneic
      conditions. Here, we focused our studies on the interaction of human NPCs and
      microglia utilizing a co-culture model. In co-cultures, both NPCs and microglia
      showed increased survival and proliferation compared with mono-cultures. In the
      presence of microglia, a larger subpopulation of NPCs expressed the progenitor
      cell marker nestin, whereas a smaller group of NPCs expressed the neural markers
      polysialylated neural cell adhesion molecule, A2B5 and glial fibrillary acidic
      protein compared with NPC mono-cultures. Microglia thus hindered differentiation
      of NPCs. The presence of human NPCs increased microglial phagocytosis of latex
      beads. Furthermore, we observed that the expression of CD200 molecules on NPCs
      and the CD200 receptor protein on microglia was enhanced in co-cultures, whereas
      the release of transforming growth factor-beta was increased suggesting anti
      inflammatory features of the co-cultures. To conclude, the interplay between
      human allogeneic NPCs and microglia, significantly affected their respective
      proliferation and phenotype. Neural cell therapy including human donor NPCs may
      in addition to offering cell replacement, modulate host microglial phenotypes and
      functions to benefit neuroprotection and repair. 

PMID- 24034598
TI  - HeFPipe: a complete analytical pipeline for heterozygosity-fitness correlation
      studies.
AB  - As the body of heterozygosity-fitness correlation (HFC) research grows, more and
      increasingly complicated tests have become an integral part of a typical HFC
      analysis (Chapman et al. 2009). Currently, no software is available to undertake
      conversion between the file formats required to conduct all of these tests and to
      conduct the main regression analyses at the core of all HFCs. Heterozygosity
      Fitness Pipeline (HeFPipe) is a script written in Python that accomplishes both
      of these tasks for studies based on microsatellite data. HeFPipe is designed to
      be used from the command line terminal and will run on any Mac OSX computer. The
      script takes input in the form of allele reports from either the genotype-calling
      software, GeneMapper or GeneMarker, and reconfigures the data into GENEPOP
      (Raymond & Rousset 1995), Rhh (Alho et al. 2010), RMES (David et al. 2007) and
      GEPHAST (Amos & Acevedo-Whitehouse 2009) formats. The script is also equipped to
      reformat the output from GENEPOP on the Web (option 5) and Rhh into csv
      spreadsheets that can be incorporated into downstream analyses. HeFPipe
      accommodates user-provided lists of samples and markers to be included in or
      excluded from analyses. HeFPipe is equipped to create generalized linear models
      (GLMs) from both the main data set and subsets of the data. Finally, HeFPipe
      allows users to explore single-marker effects and conduct correlation analyses.
      The script, a comprehensive manual, a link to a series of video tutorials, and an
      example data set are available from GitHub
      (http://github.com/Atticus29/HeFPipe_rpos). 

PMID- 24034600
TI  - Influence of Micro Threads Alteration on Osseointegration and Primary Stability
      of Implants: An FEA and In Vivo Analysis in Rabbits.
AB  - PURPOSE: To describe the early bone tissue response to implants with and without
      micro threads designed to the full length of an oxidized titanium implant.
      MATERIALS AND METHODS: A pair of two-dimensional finite element models was
      designed using a computer aided three-dimensional interactive application files
      of an implant model with micro threads in between macro threads and one without
      micro threads. Oxidized titanium implants with (test implants n=20) and without
      (control implants n=20) micro thread were prepared. A total of 12 rabbits were
      used and each received four implants. Insertion torque while implant placement
      and removal torque analysis after 4 weeks was performed in nine rabbits, and
      histomorphometric analysis in three rabbits, respectively. RESULTS: Finite
      element analysis showed less stress accumulation in test implant models with
      31Mpa when compared with 62.2 Mpa in control implant model. Insertion and removal
      torque analysis did not show any statistical significance between the two implant
      designs. At 4 weeks, there was a significant difference between the two groups in
      the percentage of new bone volume and bone-to-implant contact in the femur (p<
      .05); however, not in the tibia. CONCLUSIONS: The effect of micro threads was
      prominent in the femur suggesting that micro threads promote bone formation. The
      stress distribution supported by the micro threads was especially effective in
      the cancellous bone.

PMID- 24034599
TI  - Child hunger and the protective effects of Supplemental Nutrition Assistance
      Program (SNAP) and alternative food sources among Mexican-origin families in
      Texas border colonias.
AB  - BACKGROUND: Nutritional health is essential for children's growth and
      development. Many Mexican-origin children who reside in limited-resource colonias
      along the Texas-Mexico border are at increased risk for poor nutrition as a
      result of household food insecurity. However, little is known about the
      prevalence of child hunger or its associated factors among children of Mexican
      immigrants. This study determines the prevalence of child hunger and identifies
      protective and risk factors associated with it in two Texas border areas.
      METHODS: This study uses 2009 Colonia Household and Community Food Resource
      Assessment (C-HCFRA) data from 470 mothers who were randomly recruited by
      promotora-researchers. Participants from colonias near two small towns in two
      South Texas counties participated in an in-home community and household
      assessment. Interviewer-administered surveys collected data in Spanish on
      sociodemographics, federal food assistance program participation, and food
      security status. Frequencies and bivariate correlations were examined while a
      random-effects logistic regression model with backward elimination was used to
      determine correlates of childhood hunger. RESULTS: Hunger among children was
      reported in 51% (n = 239) of households in this C-HCFRA sample. Bivariate
      analyses revealed that hunger status was associated with select maternal
      characteristics, such as lower educational attainment and Mexican nativity, and
      household characteristics, including household composition, reliance on friend or
      neighbor for transportation, food purchase at dollar stores and from neighbors,
      and participation in school-based nutrition programs. A smaller percentage of
      households with child hunger participated in school-based nutrition programs
      (51%) or used alternative food sources, while 131 households were unable to give
      their child or children a balanced meal during the school year and 145 households
      during summer months. In the random effects model (RE = small town), increased
      household composition, full-time unemployment, and participation in the National
      School Lunch Program were significantly associated with increased odds for child
      hunger, while participation in Supplemental Nutrition Assistance Program (SNAP)
      and purchasing food from a neighbor were significantly associated with decreased
      odds for child hunger. CONCLUSIONS: This study not only emphasizes the alarming
      rates of child hunger among this sample of Mexican-origin families, but also
      identifies economic and family factors that increased the odds for child hunger
      as well as community strategies that reduced the odds. It is unsettling that so
      many children did not participate in school-based nutrition programs, and that
      many who participated in federal nutrition assistance programs remained hungry.
      This study underscores the importance of identifying the presence of child hunger
      among low-income Mexican-origin children in Texas border colonias and increasing
      access to nutrition-related resources. Hunger-associated health inequities at
      younger ages among colonia residents are likely to persist across the life span
      and into old age.

PMID- 24034601
TI  - Single-nucleotide polymorphisms of IRF8 gene are associated with systemic lupus
      erythematosus in Chinese Han population.
AB  - Interferon regulatory factor 8 (IRF8) has been shown to have diverse roles in the
      regulation of the immune system. Two recent studies had revealed the association
      between the single-nucleotide polymorphisms (SNPs; rs11644034 and rs2280381) of
      IRF8 and systemic lupus erythematosus (SLE) in a multiethnic population. The
      purpose of this study was to evaluate whether the association could be replicated
      in a Chinese Han population. Genotypes were determined by a multiplex polymerase
      chain reaction-ligase detection reaction (PCR-LDR) in 358 patients and 357
      geographically matched healthy controls. Significant differences in genotype
      frequency were found between SLE and control individuals (rs11644034: AA vs. GG,
      P = 0.014, odds ratio (OR) = 0.980, 95% confidence internal (CI): 0.964-0.996;
      rs2280381: CC vs. TT, P = 0.005, OR = 0.150, 95% CI: 0.033-0.676). Conditional
      logistic regression analysis showed that the association of rs2280381 remained
      significant (P adjusted = 0.028) after adjustment for rs11644034, but not vice
      versa (P adjusted = 0.361).When stratifying patients with SLE according to
      clinical subtypes, SNP rs2280381 was found to be associated with low complement
      in patients with SLE. However, SNP rs11644034 was not found to be associated with
      SLE clinical subgroups. Analysis of the haplotypes revealed that haplotype G-T
      and G-C were also significantly associated with SLE (P = 0.002 and P = 0.012,
      respectively). Our study indicated that the IRF8 gene polymorphisms might be
      associated with susceptibility to SLE and with disease-related clinical
      manifestations in Chinese Han population.

PMID- 24034602
TI  - Pelvic organ prolapse after subtotal and total hysterectomy: a long-term follow
      up of an open randomised controlled multicentre study.
AB  - OBJECTIVE: To analyse the development of pelvic organ prolapse (POP) after
      subtotal (SH) and total hysterectomy (TH) in the long-term, and to assess patient
      reported symptoms regarding pelvic floor dysfunction (PFD). DESIGN: Long-term
      follow-up study of a randomised controlled multicentre study. SETTING: Seven
      hospitals and one private clinic in the south-east of Sweden. POPULATION: Of the
      184 women who were eligible from the original trial, 151 (82%) responded to a
      postal questionnaire and 128 (70%) were clinically examined. METHODS: Postal
      questionnaire using the short-form version of the Pelvic Floor Distress Inventory
      (PFDI-20) and clinical examination using the POP-Q system. Multivariate analyses
      were used. MAIN OUTCOME MEASURES: POP-Q measurements and symptoms of PFD.
      RESULTS: Follow-up time was a median of 11.3 years. Less than 3% had stage-3
      prolapse. No significant difference was found in the presence of stage-2 or
      higher stage prolapse between the two hysterectomy groups (39% in SH versus 37%
      in TH; OR 1.28, 95% CI 0.59-2.80). Nor was there any significant difference in
      the quality-of-life measurement between the SH and TH groups [summary score PFDI
      20: median 93 (range 60-201) versus 87 (range 60-186); Fisher's protected least
      significant difference post hoc test, P = 0.78 ). None of the symptoms of PFD
      revealed statistically significant differences between the hysterectomy groups.
      CONCLUSIONS: This long-term follow-up study of PFD showed basically no
      significant differences in subjective or objective measurements of POP, or in
      specific pelvic floor quality-of-life aspects after SH and TH. However, because
      of the low statistical power the results are inconclusive. Larger trials, and
      probably also a longer follow-up period, are necessary.

PMID- 24034604
TI  - A pair of chiral flavonolignans as novel anti-cyanobacterial allelochemicals
      derived from barley straw (Hordeum vulgare): characterization and comparison of
      their anti-cyanobacterial activities.
AB  - The inhibitory effect of barley straw (Hordeum vulgare) on cyanobacteria has been
      observed in many field and laboratory studies for over 30 years, although the
      compounds responsible for this anti-cyanobacterial effect have remained unknown.
      In this study, a pair of chiral flavonolignans were isolated from barley straw
      extract using a bioassay-guided isolation procedure against Microcystis sp. The
      structures of the allelopathic compounds were elucidated by NMR (nuclear magnetic
      resonance) and HPLC-MS (high performance liquid chromatography-mass
      spectrometry), and turned out to be salcolin A and B. The enantiomers differ in
      their anti-cyanobacterial abilities. Both enantiomers exhibited inhibitory
      effects on Microcystis sp., and the EC50 (concentration for 50% of maximal
      effect) of salcolin A and B were 6.02 * 10(-5) and 9.60 * 10(-5 ) mol l(-1) ,
      respectively. Furthermore, the modes of actions of the enantiomers were
      investigated and compared at a single cell level by flow cytometry. Salcolin A
      was found to induce an increase on cyanobacterial intracellular ROS (reactive
      oxygen species) levels and to inhibit esterase activity, whereas salcolin B
      caused leakages of cyanobacterial cytoplasms. Thus, salcolin A was more
      'algistatic', and salcolin B was more 'algicidal'. This study suggests that
      salcolin is the key allelochemical in barley straw's inhibitory effect on
      cyanobacteria and could be used as an agent in the future control of
      cyanobacterial harmful algae blooms. 

PMID- 24034603
TI  - Genome and transcriptome sequencing of the halophilic fungus Wallemia
      ichthyophaga: haloadaptations present and absent.
AB  - BACKGROUND: The basidomycete Wallemia ichthyophaga from the phylogenetically
      distinct class Wallemiomycetes is the most halophilic fungus known to date. It
      requires at least 10% NaCl and thrives in saturated salt solution. To investigate
      the genomic basis of this exceptional phenotype, we obtained a de-novo genome
      sequence of the species type-strain and analysed its transcriptomic response to
      conditions close to the limits of its lower and upper salinity range. RESULTS:
      The unusually compact genome is 9.6 Mb large and contains 1.67% repetitive
      sequences. Only 4884 predicted protein coding genes cover almost three quarters
      of the sequence. Of 639 differentially expressed genes, two thirds are more
      expressed at lower salinity. Phylogenomic analysis based on the largest dataset
      used to date (whole proteomes) positions Wallemiomycetes as a 250-million-year
      old sister group of Agaricomycotina. Contrary to the closely related species
      Wallemia sebi, W. ichthyophaga appears to have lost the ability for sexual
      reproduction. Several protein families are significantly expanded or contracted
      in the genome. Among these, there are the P-type ATPase cation transporters, but
      not the sodium/ hydrogen exchanger family. Transcription of all but three cation
      transporters is not salt dependent. The analysis also reveals a significant
      enrichment in hydrophobins, which are cell-wall proteins with multiple cellular
      functions. Half of these are differentially expressed, and most contain an
      unusually large number of acidic amino acids. This discovery is of particular
      interest due to the numerous applications of hydrophobines from other fungi in
      industry, pharmaceutics and medicine. CONCLUSIONS: W. ichthyophaga is an
      extremophilic specialist that shows only low levels of adaptability and genetic
      recombination. This is reflected in the characteristics of its genome and its
      transcriptomic response to salt. No unusual traits were observed in common salt
      tolerance mechanisms, such as transport of inorganic ions or synthesis of
      compatible solutes. Instead, various data indicate a role of the cell wall of W.
      ichthyophaga in its response to salt. Availability of the genomic sequence is
      expected to facilitate further research into this unique species, and shed more
      light on adaptations that allow it to thrive in conditions lethal to most other
      eukaryotes.

PMID- 24034605
TI  - Selection for reluctance to avoid humans during the domestication of mice.
AB  - Many animal species have been domesticated over the course of human history and
      became tame as a result of domestication. Tameness is a behavioral characteristic
      with 2 potential components: (1) reluctance to avoid humans and (2) motivation to
      approach humans. However, the specific behavioral characteristics selected during
      domestication processes remain to be clarified for many species. To quantify
      these 2 different components of tameness separately, we established 3 behavioral
      tests: the 'active tame', 'passive tame' and 'stay-on-hand' tests. We subjected
      genetically diverse mouse strains to these tests, including 10 wild strains
      (BFM/2Ms, PGN2/Ms, HMI/Ms, BLG2/Ms, NJL/Ms, KJR/Ms, SWN/Ms, CHD/Ms, MSM/Ms and
      CAST/Ei), a fancy strain (JF1/Ms) and 6 standard laboratory strains (C3H/HeNJcl,
      CBA/J, BALB/cAnNCrlCrlj, DBA/2JJcl, 129(+Ter) /SvJcl and C57BL/6JJcl). To analyze
      the effects of domestication, these 17 strains were divided into 2 groups:
      domesticated strains (fancy and laboratory strains) and wild strains. Significant
      differences between strains were observed in all traits, and the calculated
      estimates of broad-sense heritability were 0.15-0.72. These results illustrate
      that tameness in mice is significantly influenced by genetic background. In
      addition, they clearly show the differences in the features of tameness in
      domesticated and wild strains. Most of the domesticated strains showed
      significantly greater reluctance to avoid humans than wild strains, whereas there
      was no significant difference in the level of motivation to approach humans
      between these 2 groups. These results might help to clarify the genetic basis of
      tameness in mice.

PMID- 24034607
TI  - Finding a sugary foothold: how antibiotics pave the way for enteric pathogens.
AB  - Antibiotic therapy predisposes the host to infections with human enteropathogens.
      In a recent study, Ng et al. (2013) demonstrate that antibiotic-mediated
      disruption of the microbial food web gives rise to free microbiota-liberated
      monosaccharides in the gut, which can promote growth of enteropathogenic
      bacteria.

PMID- 24034606
TI  - Automated quantification of the subcellular localization of multicompartment
      proteins via Q-SCAn.
AB  - In eukaryotic cells, proteins can occupy multiple intracellular compartments and
      even move between compartments to fulfill critical biological functions or
      respond to cellular signals. Examples include transcription factors that reside
      in the cytoplasm but are mobilized to the nucleus as well as dual-purpose DNA
      repair proteins that are charged with simultaneously maintaining the integrity of
      both the nuclear and mitochondrial genomes. While numerous methods exist to study
      protein localization and dynamics, automated methods to quantify the relative
      amounts of proteins that occupy multiple subcellular compartments have not been
      extensively developed. To address this need, we present a rapid, automated method
      termed quantitative subcellular compartmentalization analysis (Q-SCAn). To
      develop this method, we exploited the facile molecular biology of the budding
      yeast, Saccharomyces cerevisiae. Individual subcellular compartments are defined
      by a fluorescent marker protein and the intensity of a target GFP-tagged protein
      is then quantified within each compartment. To validate Q-SCAn, we analyzed
      relocalization of the transcription factor Yap1 following oxidative stress and
      then extended the approach to multicompartment localization by examining two DNA
      repair proteins critical for the base excision repair pathway, Ntg1 and Ung1. Our
      findings demonstrate the utility of Q-SCAn for quantitative analysis of the
      subcellular distribution of multicompartment proteins. 

PMID- 24034608
TI  - Cholera toxin notches epithelial junctions.
AB  - Cholera toxin (CT) is the factor responsible for watery diarrhea associated with
      Vibrio cholerae infection. In this issue, Guichard et al. (2013) report that CT
      compromises intestinal epithelium barrier function via cyclic AMP (cAMP)-induced
      disruption of Rab11- and exocyst-dependent delivery of endocytic recycling cargo
      to cell-cell junctions.

PMID- 24034609
TI  - Host restriction factor screening: let the virus do the work.
AB  - In this issue of Cell Host & Microbe, Varble et al. (2013) engineer a library of
      RNA viruses to express small interfering RNAs and couple this with the power of
      virus evolution and selection to screen for host genes that when silenced
      resulted in greater viral infection in vivo.

PMID- 24034610
TI  - Virus budding and the ESCRT pathway.
AB  - Enveloped viruses escape infected cells by budding through limiting membranes. In
      the decade since the discovery that HIV recruits cellular ESCRT (endosomal
      sorting complexes required for transport) machinery to facilitate viral budding,
      this pathway has emerged as the major escape route for enveloped viruses. In
      cells, the ESCRT pathway catalyzes analogous membrane fission events required for
      the abscission stage of cytokinesis and for a series of "reverse topology"
      vesiculation events. Studies of enveloped virus budding are therefore providing
      insights into the complex cellular mechanisms of cell division and membrane
      protein trafficking (and vice versa). Here, we review how viruses mimic cellular
      recruiting signals to usurp the ESCRT pathway, discuss mechanistic models for
      ESCRT pathway functions, and highlight important research frontiers. 

PMID- 24034611
TI  - Arp2/3-mediated actin-based motility: a tail of pathogen abuse.
AB  - Intracellular pathogens have developed elaborate mechanisms to exploit the
      different cellular systems of their unwilling hosts to facilitate their entry,
      replication, and survival. In particular, a diverse range of bacteria and viruses
      have evolved unique strategies to harness the power of Arp2/3-mediated actin
      polymerization to enhance their cell-to-cell spread. In this review, we discuss
      how studying these pathogens has revolutionized our molecular understanding of
      Arp2/3-dependent actin assembly and revealed key signaling pathways regulating
      actin assembly in cells. Future analyses of microbe-host interactions are likely
      to continue uncovering new mechanisms regulating actin assembly and dynamics, as
      well as unexpected cellular functions for actin. Further, studies with known and
      newly emerging pathogens will also undoubtedly continue to enhance our
      understanding of the role of the actin cytoskeleton during pathogenesis and
      potentially highlight future therapeutic approaches.

PMID- 24034612
TI  - A Rab-centric perspective of bacterial pathogen-occupied vacuoles.
AB  - The ability to create and maintain a specialized organelle that supports
      bacterial replication is an important virulence property for many intracellular
      pathogens. Living in a membrane-bound vacuole presents inherent challenges,
      including the need to remodel a plasma membrane-derived organelle into a novel
      structure that will expand and provide essential nutrients to support
      replication, while also having the vacuole avoid membrane transport pathways that
      target bacteria for destruction in lysosomes. It is clear that pathogenic
      bacteria use different strategies to accomplish these tasks. The dynamics by
      which host Rab GTPases associate with pathogen-occupied vacuoles provide insight
      into the mechanisms used by different bacteria to manipulate host membrane
      transport. In this review we highlight some of the strategies bacteria use to
      maintain a pathogen-occupied vacuole by focusing on the Rab proteins involved in
      biogenesis and maintenance of these novel organelles. 

PMID- 24034613
TI  - What pathogens have taught us about posttranslational modifications.
AB  - Pathogens use various mechanisms to manipulate host processes to promote
      infection. Decades of research on pathogens have revealed not only the molecular
      mechanisms that these microbes use to replicate and survive within host cells,
      but also seminal information on how host signaling machinery regulates cellular
      processes. Among these discoveries are mechanisms involving posttranslational
      modifications that alter the activity, localization, or interactions of the
      modified protein. Herein, we examine how pathogens have contributed to our basic
      understanding of three posttranslational modifications: phosphorylation,
      NMPylation, and ubiquitylation. Over the years, technologies, techniques and
      research tools have developed side by side with the study of pathogens,
      facilitating the discovery of protein modifications and furthering our
      understanding of how they contribute to both infection and cellular functions.

PMID- 24034614
TI  - Enteroviruses harness the cellular endocytic machinery to remodel the host cell
      cholesterol landscape for effective viral replication.
AB  - Cholesterol is a critical component of cellular membranes, regulating assembly
      and function of membrane-based protein/lipid complexes. Many RNA viruses,
      including enteroviruses, remodel host membranes to generate organelles with
      unique lipid blueprints on which they assemble replication complexes and
      synthesize viral RNA. Here we find that clathrin-mediated endocytosis (CME) is
      harnessed by enteroviruses to traffic cholesterol from the plasma membrane (PM)
      and extracellular medium to replication organelles, where cholesterol then
      regulates viral polyprotein processing and facilitates genome synthesis. When CME
      is disrupted, cellular cholesterol pools are instead stored in lipid droplets,
      cholesterol cannot be trafficked to replication organelles, and replication is
      inhibited. In contrast, replication is stimulated in cholesterol-elevated cells
      like those lacking caveolins or those from Niemann-Pick disease patients. Our
      findings indicate cholesterol as a critical determinant for enteroviral
      replication and outline roles for the endocytic machinery in both the enteroviral
      life cycle and host cell cholesterol homeostasis.

PMID- 24034615
TI  - Cholera toxin disrupts barrier function by inhibiting exocyst-mediated
      trafficking of host proteins to intestinal cell junctions.
AB  - Cholera toxin (CT), a virulence factor elaborated by Vibrio cholerae, is
      sufficient to induce the severe diarrhea characteristic of cholera. The enzymatic
      moiety of CT (CtxA) increases cAMP synthesis in intestinal epithelial cells,
      leading to chloride ion (Cl(-)) efflux through the CFTR Cl(-) channel. To
      preserve electroneutrality and osmotic balance, sodium ions and water also flow
      into the intestinal lumen via a paracellular route. We find that CtxA-driven cAMP
      increase also inhibits Rab11/exocyst-mediated trafficking of host proteins
      including E-cadherin and Notch signaling components to cell-cell junctions in
      Drosophila, human intestinal epithelial cells, and ligated mouse ileal loops,
      thereby disrupting barrier function. Additionally, CtxA induces junctional
      damage, weight loss, and dye leakage in the Drosophila gut, contributing to
      lethality from live V. cholerae infection, all of which can be rescued by Rab11
      overexpression. These barrier-disrupting effects of CtxA may act in parallel with
      Cl(-) secretion to drive the pathophysiology of cholera.

PMID- 24034616
TI  - Identifying Yersinia YopH-targeted signal transduction pathways that impair
      neutrophil responses during in vivo murine infection.
AB  - Identifying molecular targets of Yersinia virulence effectors, or Yops, during
      animal infection is challenging because few cells are targeted by Yops in an
      infected organ, and isolating these sparse effector-containing cells is
      difficult. YopH, a tyrosine phosphatase, is essential for full virulence of
      Yersinia. Investigating the YopH-targeted signal transduction pathway(s) in
      neutrophils during infection of a murine host, we find that several host
      proteins, including the essential signaling adaptor SLP-76, are dephosphorylated
      in the presence of YopH in neutrophils isolated from infected tissues. YopH
      inactivated PRAM-1/SKAP-HOM and the SLP-76/Vav/PLCgamma2 signal transduction
      axes, leading to an inhibition of calcium response in isolated neutrophils.
      Consistent with a failure to mount a calcium response, IL-10 production was
      reduced in neutrophils containing YopH from infected tissues. Finally, a yopH
      mutant survived better in the absence of neutrophils, indicating that neutrophil
      inactivation by YopH by targeting PRAM-1/SKAP-HOM and SLP-76/Vav/PLCgamma2
      signaling hubs may be critical for Yersinia survival.

PMID- 24034617
TI  - Intraluminal containment of commensal outgrowth in the gut during infection
      induced dysbiosis.
AB  - Shifts in commensal microbiota composition are emerging as a hallmark of
      gastrointestinal inflammation. In particular, outgrowth of gamma-proteobacteria
      has been linked to the etiology of inflammatory bowel disease and the pathologic
      consequences of infections. Here we show that following acute Toxoplasma gondii
      gastrointestinal infection of mice, control of commensal outgrowth is a highly
      coordinated process involving both the host response and microbial signals.
      Notably, neutrophil emigration to the intestinal lumen results in the generation
      of organized intraluminal structures that encapsulate commensals and limit their
      contact with the epithelium. Formation of these luminal casts depends on the high
      affinity N-formyl peptide receptor, Fpr1. Consequently, after infection, mice
      deficient in Fpr1 display increased microbial translocation, poor commensal
      containment, and increased mortality. Altogether, our study describes a mechanism
      by which the host rapidly contains commensal pathobiont outgrowth during
      infection. Further, these results reveal Fpr1 as a major mediator of host
      commensal interaction during dysbiosis.

PMID- 24034618
TI  - Alterations in the gut microbiota associated with HIV-1 infection.
AB  - Understanding gut microbiota alterations associated with HIV infection and
      factors that drive these alterations may help explain gut-linked diseases
      prevalent with HIV. 16S rRNA sequencing of feces from HIV-infected individuals
      revealed that HIV infection is associated with highly characteristic gut
      community changes, and antiretroviral therapy does not consistently restore the
      microbiota to an HIV-negative state. Despite the chronic gut inflammation
      characteristic of HIV infection, the associated microbiota showed limited
      similarity with other inflammatory states and instead showed increased, rather
      than decreased, diversity. Meta-analysis revealed that the microbiota of HIV
      infected individuals in the U.S. was most similar to a Prevotella-rich community
      composition typically observed in healthy individuals in agrarian cultures of
      Malawi and Venezuela and related to that of U.S. individuals with carbohydrate
      rich, protein- and fat-poor diets. By evaluating innate and adaptive immune
      responses to lysates from bacteria that differ with HIV, we explore the
      functional drivers of these compositional differences.

PMID- 24034619
TI  - SIV-induced instability of the chimpanzee gut microbiome.
AB  - Simian immunodeficiency virus of chimpanzees (SIVcpz) is the ancestor of human
      immunodeficiency virus type 1 (HIV-1), the etiologic agent of acquired
      immunodeficiency syndrome (AIDS) in humans. Like HIV-1-infected humans, SIVcpz
      infected chimpanzees can develop AIDS-like symptoms. Because SIVcpz/HIV-1 may
      disrupt regulation of the gut microbiome and because it has not been possible to
      sample individual humans pre- and postinfection, we investigated the influence of
      infection on gut communities through long-term monitoring of chimpanzees from
      Gombe National Park, Tanzania. SIVcpz infection accelerated the rate of change in
      gut microbiota composition within individuals for periods of years after the
      initial infection and led to gut communities marked by high frequencies of
      pathogen-containing bacterial genera absent from SIVcpz-negative individuals. Our
      results indicate that immune function maintains temporally stable gut communities
      that are lost when individuals become infected with SIVcpz.

PMID- 24034620
TI  - An in vivo RNAi screening approach to identify host determinants of virus
      replication.
AB  - RNA interference (RNAi) has been extensively used to identify host factors
      affecting virus infection but requires exogenous delivery of short interfering
      RNAs (siRNAs), thus limiting the technique to nonphysiological infection models
      and a single defined cell type. We report an alternative screening approach using
      siRNA delivery via infection with a replication-competent RNA virus. In this
      system, natural selection, defined by siRNA production, permits the
      identification of host restriction factors through virus enrichment during a
      physiological infection. We validate this approach with a large-scale siRNA
      screen in the context of an in vivo alphavirus infection. Monitoring virus
      evolution across four independent screens identified two categories of enriched
      siRNAs: specific effectors of the direct antiviral arsenal and host factors that
      indirectly dampened the overall antiviral response. These results suggest that
      pathogenicity may be defined by the ability of the virus to antagonize broad
      cellular responses and specific antiviral factors.

PMID- 24034621
TI  - A transcriptomic network identified in uninfected macrophages responding to
      inflammation controls intracellular pathogen survival.
AB  - Intracellular pathogens modulate host cell function to promote their survival.
      However, in vitro infection studies do not account for the impact of host-derived
      inflammatory signals. Examining the response of liver-resident macrophages
      (Kupffer cells) in mice infected with the parasite Leishmania donovani, we
      identified a transcriptomic network operating in uninfected Kupffer cells exposed
      to inflammation but absent from Kupffer cells from the same animal that contained
      intracellular Leishmania. To test the hypothesis that regulated expression of
      genes within this transcriptomic network might impact parasite survival, we
      pharmacologically perturbed the activity of retinoid X receptor alpha (RXRalpha),
      a key hub within this network, and showed that this intervention enhanced the
      innate resistance of Kupffer cells to Leishmania infection. Our results
      illustrate a broadly applicable strategy for understanding the host response to
      infection in vivo and identify Rxra as the hub of a gene network controlling
      antileishmanial resistance.

PMID- 24034622
TI  - [Severe obstruction of the airway due to a large laterocervical mass].

PMID- 24034623
TI  - [Downward displacement of the pleura after administration of local anesthetic
      into thoracic paravertebral space].

PMID- 24034624
TI  - Rapid detection of Akabane virus by a novel reverse transcription loop-mediated
      isothermal amplification assay (RT-LAMP).
AB  - BACKGROUND: Akabane disease, caused by Akabane virus, is an insect-transmitted
      disease of ruminants that is primarily characterized by fetal damage. METHODS AND
      RESULTS: In this study, a novel reverse transcription loop-mediated isothermal
      amplification (RT-LAMP) assay for rapid detection of Akabane virus was
      successfully developed. The primers were designed to target the highly conserved
      fragment of nucleoprotein from the Akabane virus. The results indicate that the
      assay is highly specific and sensitive with a detection limit of 5.0 TCID50/mL
      within a 60-min incubation time. A total of 126 abortive samples collected from
      Xinjiang province were detected by the established RT-LAMP. The results of RT
      LAMP assay showed 96.8% agreement with the semi-nested RT-PCR. CONCLUSION: This
      study is to first to develop a rapid, sensitive, and accurate method for the
      detection of Akabane virus, which may be used to screen clinical samples in
      developing countries or regions.

PMID- 24034625
TI  - Polypectomy in patients with a family history of colorectal cancer may lead to
      inadequate surveillance and missed cancers in their kindred.

PMID- 24034626
TI  - Emergence of H3N2pM-like and novel reassortant H3N1 swine viruses possessing
      segments derived from the A (H1N1)pdm09 influenza virus, Korea.
AB  - BACKGROUND: Human-to-swine transmission of the pandemic H1N1 2009 [A(H1N1)pdm09]
      virus in pig populations resulted in reassortment events with endemic swine
      influenza viruses worldwide. OBJECTIVE: We investigated whether A(H1N1)pdm09
      derived reassortant viruses are present in South Korea and sought to determine
      the pathogenic potential of the novel swine viruses. METHODS: Pig lung tissues
      were collected from commercially slaughtered pigs. Isolated swine influenza
      viruses were genetically analyzed and characterized in vitro and in vivo.
      RESULTS: We identified reassortant H3N2 (H3N2pM-like) and H3N1 swine viruses
      containing A(H1N1)pdm09-like segments in Korean pigs that are genetically closely
      related to strains recently detected in pigs and humans in North America.
      Although the H3N2pM-like and novel H3N1 reassortants demonstrated efficient
      replication in mice and ferrets, all the H3N1 strains exhibited growth advantage
      over the representative H3N2pM-like virus in human airway cells. Interestingly,
      A/swine/Korea/CY02-07/2012(H3N1) and A/swine/Korea/CY03-13/2012(H3N1)
      reassortants were more readily transmitted to respiratory-droplet-contact ferrets
      compared with the H3N2pM-like (A/swine/Korea/CY02-10/2012) isolate. Furthermore,
      serologic evaluation showed poor antigenicity to contemporary reference human
      seasonal H3N2 vaccine strains. CONCLUSIONS: We report here for the first time the
      isolation of H3N2pM-like viruses outside North America and of novel reassortant
      swine H3N1 viruses with A(H1N1)pdm09-derived genes. Apart from further
      complicating the genetic diversity of influenza A viruses circulating in domestic
      pigs, our data also indicate that these strains could potentially pose threat to
      public health asserting the need for continuous virus monitoring in these
      ecologically important hosts.

PMID- 24034627
TI  - Resistin affects lipid metabolism during adipocyte maturation of 3T3-L1 cells.
AB  - Resistin, an adipose-tissue-specific secretory factor, aggravates metabolic
      syndrome through impairment of glucose metabolism. Previously, we demonstrated
      that resistin expression was induced in both 3T3-L1 cells and primary pre
      adipocytes derived from Zucker obese rats during the process of differentiation
      and maturation (Ikeda Y, Hama S, Kajimoto K, Okuno T, Tsuchiya H & Kogure K
      (2011) Biol Pharm Bull 34, 865-870). However, the biological function of resistin
      in adipocytes is poorly understood. In the present study, we examined the effects
      of resistin knockdown on the biological features of 3T3-L1 cells. We found that
      lipid content was significantly decreased in 3T3-L1 cells transfected with anti
      resistin small interfering RNA (siRNA) after adipocyte differentiation. While
      expression of peroxisome proliferator activated receptor gamma and CCAAT/enhancer
      binding protein alpha was not affected, protein expression and transcriptional
      activity levels of carbohydrate response element binding protein (ChREBP), which
      upregulates transcription of lipogenic genes, decreased after anti-resistin siRNA
      treatment. Moreover, gene expression of fatty acid synthase and acetyl-CoA
      carboxylase 2, which are known to be regulated by ChREBP, were also suppressed by
      resistin knockdown. In contrast, activity of the fatty acid beta-oxidation
      regulating protein carnitine palmitoyltransferase 1 increased. These results
      suggest that resistin knockdown induces suppression of lipid production and
      activation of fatty acid beta-oxidation. Consequently, resistin may affect lipid
      metabolism during adipocyte maturation.

PMID- 24034628
TI  - The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre
      randomised controlled trial of physician prehospital management of severe blunt
      head injury compared with management by paramedics.
AB  - BACKGROUND: The utility of advanced prehospital interventions for severe blunt
      traumatic brain injury (BTI) remains controversial. Of all trauma patient
      subgroups it has been anticipated that this patient group would most benefit from
      advanced prehospital interventions as hypoxia and hypotension have been
      demonstrated to be associated with poor outcomes and these factors may be
      amenable to prehospital intervention. Supporting evidence is largely lacking
      however. In particular the efficacy of early anaesthesia/muscle relaxant assisted
      intubation has proved difficult to substantiate. METHODS: This article describes
      the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a
      randomised controlled single centre trial of physician prehospital care
      (delivering advanced interventions such as rapid sequence intubation and blood
      transfusion) in addition to paramedic care for severe blunt TBI compared with
      paramedic care alone. RESULTS: Primary endpoint is Glasgow Outcome Scale score at
      six months post injury. Issues with trial integrity resulting from drop ins from
      standard care to the treatment arm as the result of policy changes by the local
      ambulance system are discussed. CONCLUSION: This randomised controlled trial will
      contribute to the evaluation of the efficacy of advance prehospital interventions
      in severe blunt TBI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00112398.

PMID- 24034630
TI  - Does the correspondence between EQ-5D health state description and VAS score vary
      by medical condition?
AB  - BACKGROUND: The EQ-5D health-related quality of life instrument comprises a
      health state classification (health problems by severity in five domains),
      followed by an evaluation using a visual analogue scale (VAS). Despite the EQ
      5D's use in health technology assessment and as a patient-reported outcome
      measure (PROM), the correspondence between the two parts of the instrument
      remains ill-understood. In this paper, we consider whether the association
      between health state classification and VAS score might vary by medical
      condition. METHODS: EQ-5D data collected for studies of patients in four
      different clinical conditions or circumstances (stroke, low back pain,
      colposcopic investigation or cytological surveillance) were pooled to generate a
      sample of 3,851 patient records. VAS scores were regressed on reported problem
      severities, with the inclusion of intercept and slope dummy variables specific to
      condition. RESULTS: The regression model achieved a goodness-of-fit of 0.54.
      Given its structure and the significance of the coefficients, the proportion of
      VAS scores which differed by condition for the same health state varied between
      33.3 and 88.5 per cent of possible states. CONCLUSIONS: Many of the patients with
      different medical conditions or in receipt of different interventions recorded
      different VAS valuations, in spite of ostensibly being in the same EQ-5D-defined
      health states. By implication, it is probable that the same state-to-state change
      would by valued differently by patients experiencing different conditions.

PMID- 24034629
TI  - Oridonin ameliorates neuropathological changes and behavioural deficits in a
      mouse model of cerebral amyloidosis.
AB  - Alzheimer's disease (AD) is the most common form of neurodegeneration and the
      major cause of dementia. This multifactorial disorder is clinically defined by
      progressive behavioural and cognitive deficits, and neuropathologically
      characterized by beta-amyloid aggregation, hyperphosphorylated tau and
      neuroinflammation. Oridonin, a diterpenoid isolated from Chinese herb Rabdosia
      rubescens, has multiple biological properties, especially anti-inflammatory and
      neuroregulatory activities. Potential therapeutic effects of Oridonin were
      investigated in an animal model of cerebral amyloidosis for AD, transgenic
      APP/PS1 mice. Oridonin was suspended in carboxymethylcellulose or loaded with a
      nanostructured emulsion, and was orally administrated or injected. Before, during
      and following the experimental treatments, behavioural tests were performed with
      these transgenic mice and their naive littermates. Following relatively short
      term treatments of 10 days, brain tissue of mice were removed for
      immunohistochemical assays. The results indicate that both oral treatment and
      injection of Oridonin significantly attenuated beta-amyloid deposition, plaque
      associated APP expression and microglial activation in brain of transgenic mice.
      Furthermore, injection of Oridonin-nanoemulsion ameliorated deficits in nesting,
      an important affiliative behaviour, and in social interaction. Additional in
      vitro studies indicated that Oridonin effectively attenuated inflammatory
      reaction of macrophage and microglial cell lines. Our results suggest that
      Oridonin might be considered a promising therapeutic option for human AD or other
      neurodegenerative diseases. 

PMID- 24034631
TI  - Self-reported exposure to intimate partner violence among women and men in
      Sweden: results from a population-based survey.
AB  - BACKGROUND: Few population-based studies assessing IPV among randomly selected
      women and men have been conducted in Sweden. Hence, the aim of the current study
      was to explore self-reported exposure, associated factors, social and behavioural
      consequences of and reasons given for using psychological, physical and sexual
      intimate partner violence (IPV) among women and men residing in Sweden. METHODS:
      Cross-sectional postal survey of women and men aged 18-65 years. Bivariate and
      multivariate logistic regression analyses were used to identify factors
      associated with exposure to IPV. RESULTS: Past-year IPV exposure rates were
      similar in women and men; however, earlier-in-life estimates were higher in
      women. Poor to moderate social support, growing up with domestic violence and
      being single, widowed or divorced were associated with exposure to all forms of
      IPV in men and women. Women and men tended to report different social
      consequences of IPV. CONCLUSIONS: Our finding that women reported greater
      exposure to IPV earlier-in-life but not during the past year suggests the
      importance of taking this time frame into account when assessing gender
      differences in IPV. In-depth, qualitative studies that consider masculinities,
      femininities power and gender orders would be beneficial for extending and
      deepening our understanding of the gendered matter of IPV.

PMID- 24034632
TI  - DEFB1 gene 5' untranslated region (UTR) polymorphisms are marginally involved in
      inflammatory bowel disease in south Brazilians.
AB  - The possible association of three DEFB1 gene polymorphisms with susceptibility to
      develop ulcerative colitis (UC) and Crohn's disease (CD) was investigated in
      Brazilian patients and controls. Although a clear and strong association between
      functional 5'-UTR DEFB1 SNPs and susceptibility/protection to IBDs cannot be
      drawn, our results suggest a possible involvement of DEFB1 gene in inflammatory
      bowel diseases, especially with the colonic localization of Crohn's disease. 

PMID- 24034633
TI  - [Data on development of the European Standard Battery in France finally
      available!].

PMID- 24034634
TI  - [Changes in the European baseline series from 1981 to 2011 in a French
      dermatology-allergology centre].
AB  - BACKGROUND: Periodically updated, the European baseline series (EBS), first
      introduced in France in 1980, is an indispensable tool for the exploration of
      contact allergy. The aim of our study was to describe the prevalence of contact
      sensitization in a French centre between 1981 and 2011 to determine whether
      certain allergens may be deleted from the current BSE. PATIENTS, MATERIALS AND
      METHODS: A retrospective study was conducted in a department of dermatology
      allergology to analyse the results of all EBS tests performed every 10 years,
      from 1981 to 2001, and annually from 2007 to 2011. Some added allergens,
      introduced in 2010, were also studied. Changes in allergen positivity were
      analysed using a Cochran-Armitage test. RESULTS: Among the 4551 patients included
      for the 8-year period studied, the prevalence of positivity was 42.91%. The most
      common allergens in the general population were nickel sulphate (17.25%), with a
      constantly increasing prevalence, Myroxylon pereirae (10.68%), fragrance mix I
      (8.11%), cobalt chloride (6.99%) and chromium (6.33%). The least frequent
      sensitizations, with a decreasing prevalence, were found with clioquinol (0.25%),
      primin (0.54%) and benzocaine (0.55%). CONCLUSION: Due to modifications in
      exposure to allergens, the incidence of contact sensitization can change, but
      nickel sulphate sensitization is increasing despite recent European directives.
      Allergens with less than 1% of positive results could be withdrawn from the EBS,
      with benzalkonium chloride, methylisothiazolinone and lavender absolute being
      added.

PMID- 24034635
TI  - [Adverse skin reactions induced by BRAF inhibitors: a systematic review].
AB  - Recent developments and therapeutic use of selective BRAF inhibitors (e.g.
      dabrafenib and vemurafenib) have significantly improved overall survival and
      disease-free survival of patients with BRAF V600 mutation-positive metastatic
      melanoma. Despite their survival benefits, small-molecule inhibitors of BRAF are
      associated with significant and sometimes severe treatment-related dermatological
      toxicity. The most common adverse skin reactions include photosensitivity,
      induced malignant lesions of the skin such as keratoacanthomas, squamous cell
      carcinoma and new primary melanomas, as well as keratinocyte proliferation and
      differentiation dysfunctions that can manifest as skin papillomas, hand-foot skin
      reaction, keratosis pilaris-like rash, acantholytic dyskeratosis and cysts of the
      milia type. In this article, we describe the clinical and histological features
      of the cutaneous manifestations induced by vemurafenib and dabrafenib on the
      basis of our clinical experience and a literature review. The crucial role of
      dermatologists in patient management is also highlighted. 

PMID- 24034636
TI  - [Lymphangitis-associated rickettsiosis caused by Rickettsia sibirica
      mongolitimonae].
AB  - Rickettsia sibirica mongolitimonae was first isolated 20 years ago in Asia but
      has now been identified on three continents. Hyalomma spp. and Rhipicephalus
      pusillus ticks are vectors but only a small number of cases have been reported to
      date, mainly on the Mediterranean coast. This bacterium induces the lymphangitis
      associated rickettsiosis, a still unfamiliar rickettsiosis that is mainly
      characterized by fever with a rope-like lymphangitis and/or lymphadenopathy and
      skin eschar occurring after tick bites. These features are especially evocative
      if they occur in spring. Sequellae are very rare and treatment with doxycycline
      is recommended. 

PMID- 24034637
TI  - [Allergic contact dermatitis due to methoxy PEG-22 dodecyl glycol present in a
      cosmetic cold cream].
AB  - BACKGROUND: We report the case of a girl presenting acute allergic contact
      dermatitis due to methoxy PEG 22 dodecyl glycol contained in Mustela Cold Cream
      Nutriprotecteur(r). PATIENTS AND METHODS: A 6-year-old girl was referred with
      acute eczema of the face occurring within 12h of applying a new moisturizing
      cream, Mustela Cold Cream Nutriprotecteur(r). Patch tests were performed on the
      upper back using the Finn Chamber technique with the European standard series and
      the patient's own cream. Readings were performed after 2 days and the sole
      positive ++ reaction was associated with Mustela Cold Cream(r). Additional patch
      testing was carried out with the ingredients of the cream, with the sole positive
      ++ reaction again being to methoxy PEG 22 dodecyl glycol copolymer. The other
      ingredients were negative. DISCUSSION: Methoxy PEG 22 dodecyl glycol is a
      copolymer used in cosmetics as an emulsion stabilizer and viscosity-increasing
      agent. It is found in 20 cosmetics currently on the market, most of which are
      prescribed for children. CONCLUSION: Although it is rare, doctors must be aware
      of allergic contact dermatitis due to methoxy PEG 22 dodecyl glycol because of
      the extent of clinical reactions and because it chiefly affects the paediatric
      population.

PMID- 24034638
TI  - [D-penicillamine-induced pemphigus: changes in anti-32-2B immunostaining
      patterns].
AB  - BACKGROUND: It has been reported that D-penicillamine causes pemphigus that is
      typically superficial. Immunostaining with monoclonal anti-32-2B antibody
      targeting desmoglein 1 and 3 can help differentiate between drug-induced and
      classical auto-immune pemphigus. Absence of specific staining militates in favour
      of drug-induced pemphigus whilst positive staining suggests an auto-immune
      aetiology that is ongoing despite discontinuation of drug therapy. PATIENTS AND
      METHODS: A 59-year-old male patient was referred for management of superficial
      pemphigus 1 year after starting D-penicillamine treatment for scleroderma. The
      diagnosis of pemphigus was confirmed histologically (intra-epidermal cleavage,
      acantholysis and perikeratinocytes, deposition of IgG and complement C3).
      Immunochemical staining with anti-32-2B antibody was initially normal, in keeping
      with drug-induced pemphigus. Despite discontinuation of D-penicillamine,
      pemphigus recurred in 2008. A further skin biopsy was undertaken and anti-32-2B
      staining was abnormal, which is consistent with auto-immune pemphigus.
      DISCUSSION: Numerous cases of drug-induced pemphigus have been described in the
      literature. In approximately half of all cases, the pemphigus recedes after
      cessation of the causative drug. However, there have been no previous reports
      that changes over time in the immunostaining with anti-32-2B antibodies can
      mirror a change in form of pemphigus from a drug-induced type to an idiopathic
      type as well as the associated clinical feature of persistence after drug
      withdrawal. CONCLUSION: Normal staining with anti-32-2B antibody is associated
      with a favourable prognosis as regards resolution of drug-induced pemphigus.
      When, as in this case, status changes to abnormal staining, there is a risk that
      the pemphigus may become chronic despite discontinuation of therapy.

PMID- 24034639
TI  - [Nerve sheath myxoma of the hyponychium].
AB  - BACKGROUND: Nerve sheath myxoma is a rare benign tumour of the extremities that
      was long confounded with neurothekeoma. Herein, we describe a rare case of
      interest because of its site on the hyponychium. PATIENTS AND METHODS: A 31-year
      old woman presented with a painless distal tumour on the right ring finger that
      had been present for 3 to 4 years. It consisted of a firm, round nodule under the
      nail and spreading to the fingertip. Complete excision was carried out after
      cutting away the distal nail plate. Histological examination revealed a myxoid
      tumour comprising very clearly delineated lobules containing pale fusiform cells
      with small nuclear inclusions. These cells expressed S100 protein but no CD34 or
      epithelial membrane antigen (EMA). Complete excision was performed and a full
      recovery was made. DISCUSSION: This type of tumour is characteristic of nerve
      sheath myxoma, and is almost certainly of Schwannian origin, although distinct
      from Schwannoma. It is rare, occurs after the age of 35 years and is
      preferentially located in the extremities of the limbs. There has only been one
      other description of its occurrence under the fingernail, in which it was
      described as neurothekeoma. However, neurothekeoma is entirely different, being
      more cellular, with no expression of protein S100, and marked by the NKIC3
      antibody; it occurs in children or young adults, and is frequently found on the
      face. These two tumours were confused for some time, but today they must be
      completely distinguished from one another. These myxomas must be completely
      excised because of the risk of relapse. Finally, they should be distinguished
      from other myxoid tumours of the digits, certain of which can be malignant.

PMID- 24034640
TI  - [Extraneural soft tissue perineurioma of the nose].
AB  - BACKGROUND: Perineuriomas are tumours derived from the perineurial cells of the
      neural sheath. Soft tissue perineuriomas are rare. Herein, we report a case of
      perineurioma localized to the nose. CASE REPORT: A 24-year-old adult presented
      with a cutaneous nodule 1cm in diameter localized on the nose. Histologically,
      the tumour corresponded to a well-circumscribed fusocellular dermal proliferation
      organized in a storiform pattern. After surgical removal, the lesion did not
      recur. COMMENTS: Extraneural soft tissue perineurioma is usually a benign nerve
      sheath tumour composed mainly of perineurial cells. Our case occurred in a 24
      year-old Caucasian adult. The tumour generally presents as a unique cutaneous
      nodule corresponding histologically to a well-delineated dermal fusocellular
      proliferation organized in a storiform pattern that stains positive for EMA and
      negative for S100. The tumour is usually localized to the trunk and extremities.
      Location on the nose as in our patient has been rarely reported. Surgical removal
      of the tumour is the treatment of choice.

PMID- 24034641
TI  - [Epidemiological, aetiological and progression profiles of Stevens-Johnson
      syndrome and toxic epidermal necrolysis in Conakry (Guinea)].

PMID- 24034642
TI  - [Infiltrated plaque on the lip].

PMID- 24034643
TI  - [Minimal work-up for Raynaud syndrome: a consensus report. Microcirculation
      working group of the Societe francaise de medecine vasculaire].
AB  - About ten to fifteen percent of the French population suffer from Raynaud's
      phenomenon. Most of the time, it is considered as primary Raynaud's phenomenon,
      without underlying disease. The aim of this expert consensus from the
      "microcirculation group" for the French Society of Vascular Medicine and the
      French Society for Microcirculation, was to define clinical guidelines in
      patients consulting for Raynaud's phenomenon. The recommended minimal screening
      includes clinical examination, nailfold capillaroscopy and antinuclear
      antibodies. In particular, the aim of this screening is to identify patients with
      a significant risk for scleroderma, who would need a careful follow up. 

PMID- 24034644
TI  - [A history of scrofula and the royal touch].

PMID- 24034645
TI  - [Auto-immune bullous diseases autoantibodies (pemphigus, bullous pemphigoid):
      what the dermatologist must know].

PMID- 24034646
TI  - [Histopathology of Orf].

PMID- 24034647
TI  - [Adult xanthogranuloma].

PMID- 24034648
TI  - [A rapidly growing pilomatrixoma of the ear lobe].

PMID- 24034649
TI  - [Superficial plantar angiomyxoma].

PMID- 24034650
TI  - Hypertension and dementia--the elephant in the room.

PMID- 24034651
TI  - Microalbuminuria and hypertension in pregnancy: role of aldosterone and
      inflammation.
AB  - Women with a history of hypertension in pregnancy are at increased risk of
      microalbuminuria later in life. Microalbuminuria is a marker of kidney
      dysfunction frequently related to an inflammatory event. Pregnancy is a dynamic
      process characterized by immune tolerance, angiogenesis, and hormonal regulation.
      Menstruation and pregnancy are associated with a physiological inflammation,
      which is altered in preeclampsia and probably in other hypertensive situations of
      pregnancy. An imbalance between pro-oxidant factors and the ability to scavenge
      these factors produces oxidative stress, which has been evaluated in many cells,
      but leukocytes are the main source of inflammatory cytokines and experimental and
      clinical evidence support a possible role of aldosterone as a mediator of
      placental and renal damage mediated by growth factors, reactive oxygen species,
      and cytokines. Angiotensin-converting enzyme inhibitors and aldosterone receptor
      blockers are frequently effective in reducing the risk of progression of
      cardiovascular and renal disease. 

PMID- 24034652
TI  - Improved blood pressure control in the hands of the hypertension specialist:
      method, magic, or something in between?

PMID- 24034653
TI  - Hypertension in pregnancy is a risk factor for microalbuminuria later in life.
AB  - The authors aimed to compare renal function by estimated glomerular filtration
      rate and albuminuria in 3 groups of women: nulliparous women, women with a
      history of normotensive pregnancies, and women with a history of at least one
      hypertensive pregnancy. Women who participated in the second Family Blood
      Pressure Program Study visit (2000-2004) and had serum creatinine and urine
      albumin measurements (n=3015) were categorized as having had no pregnancy lasting
      >6 months (n=341), having had only normotensive pregnancies (n=2199), or having
      had at least 1 pregnancy with hypertension (n=475) based on a standardized
      questionnaire. Women who reported having had at least one pregnancy with
      hypertension were significantly more likely to be hypertensive (75.6% vs 59.4%,
      P<.001), diabetic (34.2% vs 27.3%, P<=.001), and have higher body mass index
      (32.8 vs 30.5, P<.001) than those who reported normotensive pregnancies. There
      was a significantly greater risk of microalbuminuria (urine albumin-creatinine
      ratio >25 mg/g) in those who reported at least one pregnancy with hypertension
      (odds ratio, 1.37; confidence interval, 1.02-1.85; P=.04) than in those with
      normotensive pregnancies, after adjusting for risk factors for chronic kidney and
      cardiovascular disease. Hypertension in pregnancy is associated with an increased
      risk of future microalbuminuria. 

PMID- 24034655
TI  - Masked hypertension defined by home blood pressure monitoring is associated with
      impaired flow-mediated vasodilatation in patients with cardiovascular risk
      factors.
AB  - The relationships between home blood pressure (BP), masked hypertension defined
      by home BP, and integrated flow-mediated vasodilation (FMD) response remain
      unclear. The authors enrolled 257 patients (mean age, 63.5 years; 51% men) who
      had at least one cardiovascular risk factor. FMD of the brachial artery was
      measured with a semiautomatic edge-detection algorithm. The integrated FMD
      response was calculated as the area under the dilation curve during 120 seconds
      after deflation (FMD-AUC120) and the FMD magnitude as the percentage change in
      peak diameter (DeltaFMD). Masked hypertension was defined by office BP <140/90 mm
      Hg and home BP >=135 mm Hg and/or 85 mm Hg. Home systolic BP was inversely
      correlated with FMD-AUC120 and DeltaFMD (FMD-AUC120: r=-.23, P<.001; DeltaFMD: r=
      .13, P=.041), and office systolic BP was inversely associated with FMD-AUC120 (r=
      .16, P=.011), but not with DeltaFMD. After adjusting for covariates, home
      systolic BP (beta=-.27, P=.003), but not office BP, was inversely associated with
      FMD-AUC120, whereas DeltaFMD was not associated with office or home systolic BP.
      FMD-AUC120 was significantly lower in patients with masked hypertension compared
      with those with normotension (7.7+/-6.7 vs 11.5+/-8.8 mm * s, P=.048). Home
      systolic BP and masked hypertension defined by home BP were associated with a
      decrease in FMD-AUC120.

PMID- 24034654
TI  - Blood pressure control 1 year after referral to a hypertension specialist.
AB  - Hypertension is highly prevalent and remains poorly controlled. The purpose of
      this study was to evaluate blood pressure (BP) control in patients with
      uncontrolled hypertension 1 year after referral to a hypertension specialist. A
      retrospective chart review was performed on 158 patients evaluated by a single
      hypertension specialist between 2005 and 2010 at the Penn Hypertension Program.
      Patients were included if they had at least 1 year of follow-up and had baseline
      plasma renin activity and plasma aldosterone concentration measured. Drug
      regimens were adjusted with particular attention to results of renin-aldosterone
      profiling. Mean BP of the entire cohort decreased from 149/87 mm Hg to 129/78 mm
      Hg at 1 year (P<.0001), without a significant change in the number of
      antihypertensive medications. The authors observed that referral to a
      hypertension specialist was worthwhile and associated with a significant
      reduction in BP without an increase in the number of BP medications used at 1
      year. 

PMID- 24034656
TI  - Preliminary validation of the Hypertension Self-Care Activity Level Effects (H
      SCALE) and clinical blood pressure among patients with hypertension.
AB  - This study establishes preliminary validation of a measure that assesses
      hypertension self-care activities with clinical blood pressure (BP). The
      Hypertension Self-Care Activity Level Effects (H-SCALE) was administered to
      patients with hypertension to assess levels of self-care. Patients (n=154) were
      predominantly female (68.6%) and black (79.2%). Greater adherence to self-care
      was associated with lower systolic and diastolic BP for 5 of the 6 self-care
      behaviors. Medication adherence was correlated with systolic BP (r=-0.19, P<.05)
      and weight management adherence was correlated with diastolic BP (r=-0.22, P<.05)
      after controlling for other covariates. Increased adherence to recommended
      dietary practices was strongly correlated with higher systolic (r=0.29, P<.05)
      and diastolic BP (r=0.32, P<.05). The H-SCALE was acceptable for use in clinical
      settings, and adherence to self-care was generally aligned with lower BP.
      Assessment of hypertension self-care is important when working with individuals
      to control their BP. 

PMID- 24034657
TI  - Erectile dysfunction and target organ damage in the early stages of hypertension.
AB  - The authors investigated whether erectile dysfunction (ED) in the early stages of
      hypertension is associated with heightened end-organ damage. A total of 174
      consecutive men with untreated, newly diagnosed essential hypertension (aged 50.3
      years, office blood pressure [BP] 150/98 mm Hg) were studied. All participants
      underwent 24-hour ambulatory BP monitoring, blood examination, albumin-creatinine
      ratio, carotid-femoral pulse-wave velocity assessment, and echocardiography for
      estimation of left ventricular mass index and diastolic function. Hypertensive
      men with ED (n=43, 24.7%) compared with those without ED were older (by 6.4
      years, P<.05), had greater 24-hour pulse pressure (by 4.3 mm Hg, P=.011) and a
      greater prevalence of nondipping status (72.2% vs 46.7%, P=.008), while the two
      groups did not differ in plasma glucose, lipid, creatinine, and
      albumin/creatinine ratio levels. Regarding cardiac adaptations, hypertensive men
      with ED exhibited only significantly lower tissue Doppler imaging-derived Em (by
      1.6 cm/s, adjusted P=.035), while no difference in left ventricular mass index or
      pulse wave velocity were detected. ED in the setting of untreated newly diagnosed
      essential hypertension does not have an unfavorable impact on traditional markers
      of target organ damage. This finding suggests that ED assessment might not refine
      the traditional risk stratification procedure at least in the early stages of
      hypertensive disease. 

PMID- 24034658
TI  - A randomized controlled trial of an automated telephone intervention to improve
      blood pressure control.
AB  - The objective of this study was to evaluate the effectiveness of a telephonic
      outreach program to improve blood pressure (BP) control among patients with
      hypertension. The authors identified adults 18 years and older with uncontrolled
      BP within the previous 12 months. Patients received either an automated telephone
      call advising them to have a walk-in BP check (n=31,619) or usual care
      (n=33,154). The primary outcome was BP control at 4 weeks. Significantly more
      patients who received the intervention achieved BP control compared with the
      usual care group (32.5% vs 23.7%; P<.0001). Patients in the intervention arm with
      cardiovascular disease, chronic kidney disease, or diabetes mellitus achieved
      better BP control. Older age, female sex, and having a household income above the
      median were associated with BP control. When designing quality-improvement
      interventions to increase BP control rates, health care organizations should
      consider utilizing an automated telephone outreach campaign. 

PMID- 24034659
TI  - Medication class effects on visit-to-visit variability of blood pressure
      measurements: analysis of electronic health record data in the "real world".
AB  - Blood pressure (BP) visit-to-visit variability (VVV) influences the risk of
      vascular events and mortality. Research has suggested that antihypertensive
      medication classes may differentially impact VVV. This study evaluated whether
      antihypertensive medication class differentially impacted BP VVV among
      hypertensive individuals in a clinical, "real-world" setting as well as the
      association between VVV and patient characteristics. Clinical observational data
      were extracted for adults (mean age, 63; 56% female, 86% Caucasian) with
      hypertension from the Mercy EpicCare EHR-Derived Database (MEDD) (n=183,374) who
      had at least 4 outpatient visits with BP readings. A multilevel mixed model for
      change over time estimated between- and within-subject effects on the absolute
      real VVV of systolic BP. Diuretics significantly lowered VVV (beta=-0.32[-0.39 to
      0.25]) and alpha-/beta-blockers resulted in the highest VVV (beta=0.89 [0.77
      1.00]). Being older, female, and having a higher systolic BP and certain comorbid
      conditions significantly raised VVV (P<.001). The findings from the MEDD were
      consistent in general with other research on BP VVV. However, the magnitude of
      effect of antihypertensive medication class and patient characteristics was
      relatively low (<10% of the BP VVV variance for any one variable). More research
      is needed to evaluate the extent to which the class of antihypertensive
      medication class impacts BP VVV in the outpatient setting. 

PMID- 24034660
TI  - Hierarchical modeling of patient and physician determinants of blood pressure
      outcomes in adherent vs nonadherent hypertensive patients: pooled analysis of 6
      studies with 14,646 evaluable patients.
AB  - The authors used pooled data from 6 valsartan-related studies including 3983
      adherent and 10,663 nonadherent patients to evaluate blood pressure (BP) outcomes
      in both groups after 90 days of treatment, applying hierarchical linear and
      logistic regression to identify determinants of BP outcomes. The principal
      findings were that: (1) BP outcomes were consistently better in adherent
      patients; (2) approximately a quarter of the variance in 90-day BP values was
      attributable to a physician class effect; (3) common and unique patient- and
      physician-related variables were associated with BP outcomes in both groups; (4)
      physician vigilance was associated with better outcomes, especially in adherent
      patients; and (5) adherent patients were more likely to exhibit target organ
      damage and associated events while being prescribed more complex medication
      regimens. Adherence to antihypertensive medication may be a function of prior
      line treatment failure, severity of illness, and sequelae, and the ensuing
      patient resolution to change medication behavior. 

PMID- 24034661
TI  - Determinants of achieving early blood pressure control with monotherapy in a
      primary care setting.
AB  - This study sought to identify the determinants of early blood pressure (BP)
      control associated with monotherapy in hypertensive individuals being managed in
      the primary care setting. The Valsartan Intensified Primary Care Reduction of
      Blood Pressure (VIPER-BP) study, was a multicenter, randomized controlled trial
      of an intensive approach to BP management. During a standardized run-in, 2185
      participants commenced monotherapy (valsartan 80 mg/d) for 14 to 28 days. A total
      of 1978 participants aged 59+/-12 years (60% men) completed the run-in phase. Of
      these, 15.1%, 43.5%, and 41.4% participants had an initial BP target of <=125/75,
      130/80, and 140/90 mm Hg, respectively. A total of 416 of 2185 participants
      (19.0%) subsequently achieved their individual BP target during run-in with a
      mean BP change of -22.6+/-12.1/-12.9+/-8.2 mm Hg vs -4.2+/-16.2/-3.0+/-9.6 mm Hg
      for the rest (P<.001). These early responders were more likely to be women
      (adjusted odds ratio, 1.41; 95% confidence interval, 1.10-1.80), had lower BP at
      baseline, were less likely to have been treated previously (or for less time),
      and had a less stringent BP target. An initial period of monotherapy achieved BP
      control in a high proportion of hypertensive individuals with key groups
      (including women and de novo cases) more likely to show an early BP response. 

PMID- 24034662
TI  - The impact of central blood pressure levels on the relationship between
      oscillometric and central blood pressure measurements: a multicenter invasive
      study.
AB  - The aim of this study was to investigate impact of central blood pressure (BP)
      levels and sex on the difference between central and upper arm oscillometric BP
      values. Oscillometric arterial BP measurements of 675 patients were
      simultaneously compared with values measured from the ascending aorta. The
      patients were divided into 3 groups according to systolic BP levels. The upper
      arm oscillometric device overestimated systolic BP (SBP) at low and medium BP
      levels but it underestimated SBP at high BP level. As for the effect of sex on
      differences in central and oscillometric BP, SBP was overestimated to a lesser
      degree in women than in men at low BP levels, but it was more highly
      underestimated in women than in men at high BP levels. The difference between
      oscillometric upper arm BP and aortic BP was directly affected by the patient's
      central BP level. In addition, the difference between central and oscillometric
      BP was also affected by sex factor. 

PMID- 24034663
TI  - Nebivolol monotherapy in younger adults (younger than 55 years) with
      hypertension: a randomized, placebo-controlled trial.
AB  - Nebivolol, a vasodilatory beta1-blocker, may be well suited for the hemodynamics
      of the younger hypertensive patient. In this 8-week trial, 18- to 54-year-olds
      with a diastolic blood pressure (DBP) of 95 mm Hg to 109 mm Hg who completed a 4
      week placebo-only phase were randomized to receive nebivolol (5 mg/d, titrated to
      10-20 mg/d based on achievement of blood pressure <140/90 mm Hg [n=427]) or
      placebo (n=214). Primary and secondary efficacy parameters were changes in trough
      seated DBP and systolic blood pressure (SBP), respectively. Safety parameters
      included adverse events (AEs). The baseline mean age was 45.3 years; SBP/DBP,
      154/100 mm Hg; and heart rate, 78 beats per minute. Completion rates were 91.3%
      (nebivolol) and 88.3% (placebo). At endpoint, there was a significant effect of
      nebivolol over placebo for DBP (-11.8 mm Hg vs -5.5 mm Hg, P<.001) and SBP (-13.7
      mm Hg vs -5.5 mm Hg, P<.001). Total AE rates were 34.7% (nebivolol) and 32.2%
      (placebo). Nebivolol monotherapy is efficacious and well tolerated in adults
      younger than 55 years of age with increased DBP.

PMID- 24034664
TI  - The current status of angioplasty of atherosclerotic renal artery stenosis for
      the treatment of hypertension.
AB  - Atherosclerotic renal artery stenosis, a fairly common disease of older persons,
      is a manifestation of generalized atherosclerosis, and is often associated with
      coronary artery disease. It is frequently associated with hypertension and
      impaired renal function, and is perceived by many physicians to be the cause of
      hypertension and renal failure. For this reason, they believe that hypertension
      can be cured by performing percutaneous renal artery angioplasty (PTRA) with
      stent placement. This practice has led to an increase in angioplasties,
      especially by interventional cardiologists, although the results from several
      randomized studies comparing interventional therapy with medical therapy have
      shown no significant difference between the two treatment modalities in blood
      pressure reduction or change in renal function. Similar results have been found
      by nonrandomized trials with selective PTRA. For this review, a Medline search of
      the English literature was conducted from 2006 to 2012, and 13 pertinent studies
      were selected. These studies with collateral literature will be discussed in this
      concise review. 

PMID- 24034665
TI  - Five phases of blood pressure in alcoholics.

PMID- 24034666
TI  - Allopurinol on hypertension: insufficient evidence to recommend.

PMID- 24034667
TI  - Effect of allopurinol on blood pressure (author response to Allopurinol on
      hypertension: insufficient evidence to recommend).

PMID- 24034669
TI  - Morphological and molecular marker contributions to disentangling the cryptic
      Hermeuptychia hermes species complex (Nymphalidae: Satyrinae: Euptychiina).
AB  - The genus Hermeuptychia is common and widespread through the Americas, from
      Argentina to the southern United States of America. All eight recognized species
      within Hermeuptychia are small and brown, with very similar interspecific
      external morphologies and intraspecifically variable ocelli patterns that render
      taxonomic identification based on morphology difficult. In our study, we surveyed
      variability within Hermeuptychia, and evaluated species boundaries based on
      molecular data (sequences of the 'barcode' mitochondrial DNA COI gene) and
      morphology (mainly male genitalia), using a phylogenetic approach. We found eight
      DNA-based and 12 morphological groups in our sampling. Species names were
      assigned based mainly on comparisons with male genitalia morphology descriptions
      corresponding to name-bearing type specimens. Morphological and DNA variability
      were highly congruent, with the exception of group H, the Hermeuptychia cucullina
      complex. Also, the barcode region showed a clear threshold for intra- and
      interspecific mean distances around 2%. Based on these results, we circumscribe
      the species boundaries in the genus Hermeuptychia and discuss conflicts between
      mitochondrial genes and classic morphological approaches for identifying and
      delimiting species. Our study revealed cryptic diversity within an ubiquitous
      genus of Neotropical butterflies. 

PMID- 24034668
TI  - Transcriptome profiling reveals links between ParS/ParR, MexEF-OprN, and quorum
      sensing in the regulation of adaptation and virulence in Pseudomonas aeruginosa.
AB  - BACKGROUND: The ParS/ParR two component regulatory system plays critical roles
      for multidrug resistance in Pseudomonas aeruginosa. It was demonstrated that in
      the presence of antimicrobials, ParR enhances bacterial survival by distinct
      mechanisms including activation of the mexXY efflux genes, enhancement of
      lipopolysaccharide modification through the arn operon, and reduction of the
      expression of oprD porin. RESULTS: In this study, we report on transcriptomic
      analyses of P. aeruginosa PAO1 wild type and parS and parR mutants growing in a
      defined minimal medium. Our transcriptomic analysis provides the first estimates
      of transcript abundance for the 5570 coding genes in P. aeruginosa PAO1.
      Comparative transcriptomics of P. aeruginosa PAO1 and par mutants identified a
      total of 464 genes regulated by ParS and ParR. Results also showed that mutations
      in the parS/parR system abolished expression of the mexEF-oprN operon by down
      regulating the regulatory gene mexS. In addition to the known effects on drug
      resistance genes, transcript abundances of the quorum sensing genes (rhlIR and
      pqsABCDE-phnAB) were higher in both parS and parR mutants. In accordance with
      these results, a significant portion of the ParS/ParR regulated genes belonged to
      the MexEF-OprN and quorum sensing regulons. Deletion of the par genes also led to
      increased phenazine production and swarming motility, consistent with the up
      regulation of the phenazine and rhamnolipid biosynthetic genes, respectively.
      CONCLUSION: Our results link the ParS/ParR two component signal transduction
      system to MexEF-OprN and quorum sensing systems in P. aeruginosa. These results
      expand our understanding of the roles of the ParS/ParR system in the regulation
      of gene expression in P. aeruginosa, especially in the absence of antimicrobials.

PMID- 24034670
TI  - The effect of a dentifrice containing Magnolia extract on established plaque and
      gingivitis in man: a six-month clinical study.
AB  - AIM: The aim was to evaluate the clinical effect of a dentifrice containing 0.3%
      Magnolia extract on dental plaque and gingivitis. MATERIAL AND METHODS: The trial
      was a 6-month double-blind, stratified, randomized and 2-armed parallel group
      study. Forty-six subjects in the test group brushed their teeth with a dentifrice
      containing 0.3% Magnolia extract and 48 subjects in the control group brushed
      with a placebo dentifrice. Plaque and gingivitis were assessed at baseline, 3 and
      6 months. RESULTS: There was a significantly larger gingivitis reduction in the
      Magnolia group than in the control group (0.26 +/- 0.11 versus 0.11 +/- 0.12) (P
      < 0.001). There was a greater increase in the total number of healthy gingival
      units Gingival Index (GI score 0) in the Magnolia group than in the control group
      (149% versus 31%) and a larger reduction in inflamed gingival units (GI score
      2/3) (60% versus 30%). Furthermore, at sites with similar amounts of plaque, less
      clinical signs of gingival inflammation were observed in the Magnolia group than
      in the control group. CONCLUSION: Six months' unsupervised use of a dentifrice
      containing 0.3% Magnolia extract resulted in significantly greater gingivitis
      reduction than a corresponding control dentifrice.

PMID- 24034671
TI  - Meeting the challenge of maternal choice in mode of delivery with vaginal birth
      after caesarean section: a medical, legal and ethical commentary.

PMID- 24034672
TI  - Parenting stress evaluation and behavioral syndromes in a group of pediatric
      patients with epilepsy.
AB  - The aim of the present work was to measure the amount of stress in parents of
      children with epilepsy and to determine whether and how parenting stress is
      linked to behavioral symptoms of the children. Parenting stress was measured with
      the Parenting Stress Index (PSI) and behavioral symptoms with the Child Behavior
      Checklist (CBCL). Data obtained from 26 parents of children with epilepsy were
      compared with those obtained from 31 parents of healthy children. Children with
      epilepsy obtained higher scores in all the subscales of PSI and in almost all the
      subscales of CBCL compared with healthy children. Epilepsy caused a high level of
      parenting stress and of problematic behaviors since the behavioral symptoms
      predicting the degree of parenting stress significantly differed between healthy
      children and children with epilepsy. Therefore, parents of children with epilepsy
      should be offered psychological support to cope with parenting stress and to
      improve the relationship with their children. 

PMID- 24034673
TI  - Epilepsy: What do health-care professionals in Riyadh know?
AB  - PURPOSE: The objective of this study was to report on the knowledge of epilepsy,
      as well as attitudes and practices toward individuals with epilepsy, among health
      care professionals in Riyadh, the capital city of Saudi Arabia. METHODS: A survey
      consisting of 23 questions pertaining to epilepsy awareness was distributed to
      health education workers (n=51), nutritionists (n=56), physicians (n=265),
      dentists (n=58), pharmacists (n=41), nurses (n=224), physiotherapists (n=65), and
      fifth-year medical students (n=62) in three tertiary hospitals in Riyadh.
      RESULTS: Of the 822 respondents who completed the questionnaire, 100% had heard
      about epilepsy, and 92.6% would allow their children to interact with an
      individual who has epilepsy. However, 67% of respondents would not want their
      children to marry an individual with epilepsy, 97.9% of respondents believed that
      individuals with epilepsy should have the same employment opportunities as the
      general population, 10.5% believe that supernatural power is the cause of
      epilepsy, 67.2% did not know how to deal with an individual experiencing an
      epileptic episode, and 56% did not know that surgery was a treatment option for
      individuals with epilepsy in Saudi Arabia. Of the 822 respondents, 39% would not
      abide by a physician's advice not to operate a motor vehicle because of their
      illness, 91% of whom cited problems with the public transportation system as a
      reason for disregarding the doctor's advice. When asked if the participants had
      access to any information on how to deal with epilepsy during their professional
      training, 60.3% had access to such information during their graduate studies.
      Ninety-eight percent of those with access to this information were physicians and
      health-care educators (p<0.001). Physicians and health-care educators were
      significantly more aware of epilepsy than any of the other groups. CONCLUSION:
      The level of epilepsy awareness among health-care professionals in Riyadh needs
      improvement.

PMID- 24034674
TI  - Distinct ubiquitination cascades act on the peroxisomal targeting signal type 2
      co-receptor Pex18p.
AB  - Peroxisomal matrix protein import is facilitated by cycling receptors that
      recognize their cargo proteins in the cytosol by a peroxisomal targeting sequence
      (PTS) and ferry them to the peroxisomal membrane. Subsequently, the cargo is
      translocated into the peroxisomal lumen, whereas the receptor is released to the
      cytosol for further rounds of protein import. This cycle is controlled by the
      ubiquitination status of the receptor, which is best understood for the PTS1
      receptor. While polyubiquitination of PTS-receptors results in their proteasomal
      degradation, the monoubiquitinated PTS-receptors are exported to the cytosol and
      recycled for further rounds of protein import. Here, we describe the
      identification of two ubiquitination cascades acting on the PTS2 co-receptor
      Pex18p. Using in vivo and in vitro approaches, we demonstrate that the
      polyubiquitination of Pex18p requires the ubiquitin-conjugating enzyme (E2)
      Ubc4p, which cooperates with the RING (really interesting new gene)-type
      ubiquitin-protein ligases (E3) Pex2p as well as Pex10p. Monoubiquitination of
      Pex18p depends on the E2 enzyme Pex4p (Ubc10p), which functions in concert with
      the E3 enzymes Pex12p and Pex10p. Our findings for the PTS2-pathway complement
      the data on PTS1-receptor ubiquitination and add up to a unified concept of the
      ubiquitin-based regulation of peroxisomal import. 

PMID- 24034675
TI  - C U L8ter: YouTube distracted driving PSAs use of behavior change theory.
AB  - OBJECTIVE: To examine the inclusion of health behavior theory in distracted
      driving PSAs on YouTube.com. METHODS: Two-hundred fifty PSAs were assessed using
      constructs from 4 prominent health behavior theories. A total theory score was
      calculated for each video. Multiple regression analysis was used to identify
      factors associated with higher theory scores. RESULTS: PSAs were generally
      lacking in theoretical content. Video length, use of rates/statistics, driving
      scenario depiction, and presence of a celebrity were positively associated with
      theory inclusion. CONCLUSION: Collaboration between health experts and PSA
      creators could be fostered to produce more theory-based distracted driving videos
      on YouTube.com.

PMID- 24034676
TI  - Parent and teen agreement on driving expectations prior to teen licensure.
AB  - OBJECTIVES: To examine pre-licensure agreement on driving expectations and
      predictors of teen driving expectations among parent-teen dyads. METHODS: Cross
      sectional survey of 163 parent-teen dyads. Descriptive statistics, weighted Kappa
      coefficients, and linear regression were used to examine expectations about post
      licensure teen driving. RESULTS: Teens reported high pre-licensure unsupervised
      driving (N = 79, 48.5%) and regular access to a car (N = 130, 81.8%). Parents and
      teens had low agreement on teen driving expectations (eg, after dark, kappaw =
      0.23). Each time teens currently drove to/from school, their expectation of
      driving in risky conditions post-licensure increased (beta = 0.21, p = .02).
      CONCLUSIONS: Pre-licensure improvement of parent-teen agreement on driving
      expectations are needed to have the greatest impact on preventing teens from
      driving in high risk conditions.

PMID- 24034677
TI  - Asthma indicators and neighborhood and family stressors related to urban living
      in children.
AB  - OBJECTIVE: To examine differences in asthma outcomes by levels of child-reported
      neighborhood and family stress related to urban living in a sample of children
      and their caregivers. METHODS: A total of 208 urban children with asthma, ages 6
      12 and their primary caregivers from African-American, Latino, and non-Latino
      white backgrounds were included in this study. RESULTS: Children's report of
      higher levels of stress was related to poorer asthma control. Children's report
      of stressors of urban living was associated with asthma functional limitation in
      families living below the poverty threshold. CONCLUSIONS: The results from this
      study may inform future avenues for intervention to decrease the effects of
      specific stressors associated with urban poverty that may serve as barriers to
      optimal asthma control in this high-risk group.

PMID- 24034679
TI  - Correlates of cardiorespiratory and muscular fitness among Brazilian adolescents.
AB  - OBJECTIVE: To analyze socioeconomic indicators, physical activity (PA)
      opportunities, and behavioral correlates of cardiorespiratory and muscular
      fitness among Brazilian boys and girls. METHODS: A sample of 1555 adolescents was
      randomly selected. Age- and sex-specific standard scores were calculated for each
      fitness component. RESULTS: Among boys, head of household's schooling,
      involvement in organized PA, meeting the PA recommendations, and computer/games
      use were associated with cardiorespiratory fitness. Involvement in organized PA
      and active time in Physical Education (PE) classes were predictors of muscular
      fitness. Among girls, active time in PE classes and TV watching were predictors
      of cardiorespiratory fitness. Meeting the PA recommendations was associated with
      muscular fitness. CONCLUSION: PA variables and sedentary behaviors should be
      independently considered for physical fitness promotion in youth.

PMID- 24034678
TI  - Discrimination, affect, and cancer risk factors among African Americans.
AB  - OBJECTIVES: To examine whether stress or depressive symptoms mediated
      associations between perceived discrimination and multiple modifiable behavioral
      risk factors for cancer among 1363 African American adults. METHODS:
      Nonparametric bootstrapping procedures, adjusted for sociodemographics, were used
      to assess mediation. RESULTS: Stress and depressive symptoms each mediated
      associations between discrimination and current smoking, and discrimination and
      the total number of behavioral risk factors for cancer. Depressive symptoms also
      mediated the association between discrimination and overweight/obesity (p values
      < .05). CONCLUSIONS: Discrimination may influence certain behavioral risk factors
      for cancer through heightened levels of stress and depressive symptoms.
      Interventions to reduce cancer risk may need to address experiences of
      discrimination, as well as the stress and depression they engender.

PMID- 24034680
TI  - Using quantile regression to assess disparities in medication adherence.
AB  - OBJECTIVE: To examine racial/ethnic disparities in medication adherence between
      Asian and Pacific Islander Americans and Whites. METHODS: This retrospective data
      analysis included diabetes patients enrolled in a health plan in Hawaii (N =
      43,445). For anti-diabetic, lipid-lowering, and anti-hypertensive medications,
      quantile regression was estimated at 25(th), 50(th), and 75(th) quantiles to
      examine the association with race and ethnicity, controlling for other patient
      characteristics. RESULTS: Consistently, Filipinos, Native Hawaiians, and other
      Pacific Islanders were significantly less adherent than Whites. The greatest
      disparities were found for other Pacific Islanders using lipid-lowering
      medications, with adjusted differences in medication adherence, with reductions
      relative to Whites of as much as 19% for lipid-lowering medications for the
      25(th) quantile of adherence. CONCLUSION: Whereas the large sample size
      undoubtedly contributed to the statistical significance, the large magnitude of
      the disparities, particularly for Filipinos, Native Hawaiians, and other Pacific
      Islanders, which suggests that these are meaningful differences that need to be
      addressed. The largest disparities were found at the lowest quantile suggests
      that they may be occurring among the most vulnerable populations with potentially
      poor access to care.

PMID- 24034681
TI  - Job design and ethnic differences in working women's physical activity.
AB  - OBJECTIVE: To document the role job control and schedule control play in shaping
      women's physical activity, and how it delineates educational and racial
      variability in associations of job and social control with physical activity.
      METHODS: Prospective data were obtained from a community-based sample of working
      women (N = 302). Validated instruments measured job control and schedule control.
      Steps per day were assessed using New Lifestyles 800 activity monitors. RESULTS:
      Greater job control predicted more steps per day, whereas greater schedule
      control predicted fewer steps. Small indirect associations between ethnicity and
      physical activity were observed among women with a trade school degree or less
      but not for women with a college degree. CONCLUSIONS: Low job control created
      barriers to physical activity among working women with a trade school degree or
      less. Greater schedule control predicted less physical activity, suggesting women
      do not use time "created" by schedule flexibility for personal health
      enhancement.

PMID- 24034682
TI  - Adolescent girls' exposure to physical activity-promoting environments.
AB  - OBJECTIVES: To examine self-reported exposure to a physical activity (PA)
      promoting intervention and changes to school environmental PA factors. METHODS:
      Randomly selected 8(th) grade girls in year 2 (N = 3469) and year 3 (N = 3462)
      completed surveys on exposure to the health education, PE components, PA
      programming, and PA supporting messages. Girls' perceptions of their school
      environment and an assessment of school environmental factors by principals in
      support of PA also were measured. Analysis included generalized linear mixed
      models with random effects for site and school comparing intervention and control
      schools. RESULTS: Year 2 intervention girls reported greater exposure to all 4
      components of the intervention compared to control school girls. In year 3,
      differences by treatment disappeared in all but 2 components. CONCLUSIONS:
      Intervention girls were exposed to TAAG in year 2 with effects diminishing in
      year 3.

PMID- 24034683
TI  - Motivational improvements for health behavior change from wellness coaching.
AB  - OBJECTIVES: To identify client priorities prior to wellness coaching, and examine
      motivational improvements for health behaviors on follow-up. METHODS: Clients
      completed a wellness questionnaire at baseline (before coaching) and at a 3-month
      follow-up. Overall, 177 participants (92% female, average age 42.9 (SD 11.2)
      years) were included in the analysis. Clients indicated priorities for coaching,
      and levels of importance, confidence, and readiness to change within each domain
      were compared between baseline and follow-up. RESULTS: Participants identified
      weight management as their top priority and successfully reduced their BMI.
      Participants also demonstrated significant improvements in motivation and
      confidence in most health behavior domains. CONCLUSIONS: These results provide
      further support for the effectiveness of wellness coaching for weight management
      and for improving motivational readiness for behavior change.

PMID- 24034684
TI  - Evaluation of an intervention providing HPV vaccine in schools.
AB  - OBJECTIVES: To conduct outcome and process evaluations of school-located HPV
      vaccination clinics in partnership with a local health department. METHODS:
      Temporary clinics provided the HPV vaccine to middle school girls in Guilford
      County, North Carolina, in 2009-2010. RESULTS: HPV vaccine initiation was higher
      among girls attending host schools than satellite schools (6% vs. 1%, OR = 6.56,
      CI = 3.99-10.78). Of the girls who initiated HPV vaccine, 80% received all 3
      doses. Private insurance or federal programs paid for most vaccine doses.
      CONCLUSIONS: Lessons learned for creating more effective school-health department
      partnerships include focusing on host schools and delivering several vaccines to
      adolescents, not just HPV vaccine alone.

PMID- 24034686
TI  - Comparing methods for assessing beverage intake among high school students.
AB  - OBJECTIVES: To compare 7 beverage intake survey questions against criterion data
      from 24-hour dietary recall interviews (24HrDRIs) among adolescents. METHODS:
      Data were available from 610 US high school students completing a survey and >=3
      24HrDRIs. Analyses compared mean intake (times/day) calculated from the survey to
      intake (servings/day) from the 24HrDRIs. Proportions of students reporting intake
      of >=1 times/day were compared to the 24HrDRI results. RESULTS: Survey data
      significantly correlated with 24HrDRI data (all corrected r: 0.26-0.49). Survey
      results differed from 24HrDRI results on reported intake of 5 beverages.
      CONCLUSION: Intake from these beverage questions should be reported in times/day,
      which is related to, but not a proxy for, servings/day. These questions are
      useful for population-level surveillance of beverage intake and monitoring trends
      over time.

PMID- 24034685
TI  - Estimating demand for alternatives to cigarettes with online purchase tasks.
AB  - OBJECTIVES: To explore how advertising affects demand for cigarettes and
      potential substitutes, including snus, dissolvable tobacco, and medicinal
      nicotine. METHODS: A Web-based experiment randomized 1062 smokers to see
      advertisements for alternative nicotine products or soft drinks, then complete a
      series of purchase tasks, which were used to estimate demand elasticity, peak
      consumption, and cross-price elasticity (CPE) for tobacco products. RESULTS:
      Lower demand elasticity and greater peak consumption were seen for cigarettes
      compared to all alternative products (p < .05). CPE did not differ across the
      alternative products (p <= .03). Seeing relevant advertisements was not
      significantly related to demand. CONCLUSIONS: These findings suggest
      significantly lower demand for alternative nicotine sources among smokers than
      previously revealed.

PMID- 24034687
TI  - Environmental correlates of children's physical activity and obesity.
AB  - OBJECTIVES: To examine the individual, parental, and neighborhood environment
      correlates of children's physical activity and risk of obesity. METHODS:
      Secondary data of 1514 children drawn from the Delaware Survey of Children's
      Health were used for analysis. A conceptual framework was developed based on the
      Social Determinants of Health and Environmental Health Promotion model and tested
      using structural equation modeling. RESULTS: Findings confirmed that parental
      support on physical activity and a favorable neighborhood environment predicted
      children's physical activity. However, the risk of overweight and obesity was not
      associated with parental support of physical activity and children's physical
      activity. CONCLUSIONS: Future preventive practice requires a multifaceted
      approach incorporating both individual and environmental changes.

PMID- 24034688
TI  - Rural Appalachian perspectives on heart health: social ecological contexts.
AB  - OBJECTIVE: To explore factors associated with cardiovascular disease (CVD) risk
      in Central Appalachia Kentucky to guide development of a culturally appropriate
      risk reduction intervention. METHODS: Based on community-based participatory
      research principles, 7 focus groups were conducted with 88 healthcare employees
      and residents from 6 Appalachian counties. Sessions were audio-recorded and
      transcribed. Thematic analysis was used to identify themes and sub-themes.
      RESULTS: Participants most frequently attributed CVD risk to behaviors including
      unhealthy diets, physical inactivity, and smoking, and to inadequate preventive
      care. Intrapersonal, interpersonal, sociocultural, environmental, organizational,
      and policy level influences on risk were identified. CONCLUSION: Comprehensive
      intervention guided by a social ecological framework is needed to address CVD
      risk reduction in Appalachian Kentucky communities.

PMID- 24034690
TI  - Quinolone-resistant Escherichia coli isolated from birds of prey in Portugal are
      genetically distinct from those isolated from water environments and gulls in
      Portugal, Spain and Sweden.
AB  - The influence of geographic distribution and type of habitat on the molecular
      epidemiology of ciprofloxacin resistant Escherichia coli was investigated.
      Ciprofloxacin resistant E. coli from wastewater, urban water with faecal
      contamination and faeces of gulls, pigeons and birds of prey, from Portugal,
      Spain and Sweden were compared based on multi-locus sequence typing (MLST) and
      quinolone resistance genetic determinants. Multi-locus sequence typing allowed
      the differentiation of E. coli lineages associated with birds of prey from those
      inhabiting gulls and waters. E. coli lineages of clinical relevance, such as the
      complex ST131, were detected in wastewater, streams and gulls in Portugal, Spain
      and Sweden. Quinolone resistance was due to gyrA and parC mutations, although
      distinct mutations were detected in birds of prey and in wastewater, streams and
      gulls isolates. These differences were correlated with specific MLST lineages,
      suggesting resistance inheritance. Among the plasmid-mediated quinolone
      resistance genes, only aac(6')-ib-cr and qnrS were detected in wastewater,
      streams and gulls isolates, but not in birds of prey. The horizontal transfer of
      the gene aac(6')-ib-cr could be inferred from its occurrence in different MLST
      lineages. 

PMID- 24034689
TI  - Social norms and dietary behaviors among young adults.
AB  - OBJECTIVE: To examine associations between young adults' dietary behaviors and
      perceived social norms for healthy eating. METHODS: Cross-sectional survey of
      1000 diverse college students. Associations between perceived behaviors of
      family, friends, and significant other and participants' dietary behaviors were
      examined using t-tests and linear regression. RESULTS: Young adults consumed more
      fast food if they perceived that their family, friends, or significant other did
      so (p < .003). Sugar-sweetened beverage consumption was associated with perceived
      consumption by family and friends (p < .035). Fruit and vegetable consumption and
      dinner preparation were associated with perceived behavior of friends only (p <
      .001). CONCLUSIONS: Young adults' dietary behaviors appear to reflect their
      perceptions of normative behavior, particularly among friends.

PMID- 24034691
TI  - New behavioural variant FTD criteria and clinical practice.
AB  - Since the first descriptions of circumscribed frontotemporal atrophies, and the
      first statement published by the Lund and Manchester groups, consensus clinical
      and pathological criteria for frontotemporal dementia (FTD) have been
      increasingly refined. The last international behavioural variant FTD criteria
      (FTDC) (Rascovsky et al., 2011) are the most sensitive, operational and reliable,
      for the clinical syndrome. Previously exclusion features, like early and severe
      amnestic syndrome or spatial disorientation, which turn out to be not so rare,
      are taken into account, as well as imaging, and biomarkers suggestive of other
      pathologies like Alzheimer's disease. So far, clinical features do not seem very
      helpful in predicting the underlying histopathology, although there are some
      clues, mainly related to neurological features (e.g. motor neuron disease, extra
      pyramidal symptoms or language disorders), or associated disorders (e.g. Paget
      disease of bone) or genetics. BvFTD remains a difficult diagnosis at very early
      stage, which accounts for the delay of diagnosis, especially in late onset, where
      the frontotemporal atrophy may not be striking. At very young onset, psychiatric
      diseases must be ruled out. More systematic assessment of social cognition could
      be helpful. Further biomarkers are expected. Systematic use of recent criteria,
      for BvFTD and other neurodegenerative diseases especially AD, will contribute to
      make early and correct diagnoses in excluding or suggesting alternative
      diagnoses. Post-mortem assessment, with detailed recording of clinical
      information, is essential to progress. 

PMID- 24034692
TI  - Coordination of TGF-beta signaling by ubiquitylation.
AB  - In this issue, Zhang et al. (2013) demonstrate that the ubiquitin ligase TRAF4
      associates with the TGF-beta receptors, rescuing them from degradation and
      ubiquitylating TAK1 to activate non-Smad signaling, which together promote
      metastasis of breast cancer cells. 

PMID- 24034693
TI  - Opening the Chromatin by eRNAs.
AB  - Enhancer RNAs (eRNAs) have emerged as an important component of transcriptional
      activation. In this issue, Mousavi et al. (2013) have uncovered a critical role
      for eRNAs in regulation of myogenic differentiation program through increasing
      chromatin accessibility at MyoD and MyoG loci. 

PMID- 24034694
TI  - Bacterial argonaute samples the transcriptome to identify foreign DNA.
AB  - Eukaryotic Argonautes bind small RNAs and use them as guides to find
      complementary RNA targets and induce gene silencing. Though homologs of
      eukaryotic Argonautes are present in many bacteria and archaea, their small RNA
      partners and functions are unknown. We found that the Argonaute of Rhodobacter
      sphaeroides (RsAgo) associates with 15-19 nt RNAs that correspond to the majority
      of transcripts. RsAgo also binds single-stranded 22-24 nt DNA molecules that are
      complementary to the small RNAs and enriched in sequences derived from exogenous
      plasmids as well as genome-encoded foreign nucleic acids such as transposons and
      phage genes. Expression of RsAgo in the heterologous E. coli system leads to
      formation of plasmid-derived small RNA and DNA and plasmid degradation. In a R.
      sphaeroides mutant lacking RsAgo, expression of plasmid-encoded genes is
      elevated. Our results indicate that RNAi-related processes found in eukaryotes
      are also conserved in bacteria and target foreign nucleic acids. 

PMID- 24034695
TI  - The dependence receptor TrkC triggers mitochondria-dependent apoptosis upon Cobra
      1 recruitment.
AB  - The neurotrophin receptor TrkC was recently identified as a dependence receptor,
      and, as such, it triggers apoptosis in the absence of its ligand, NT-3. The
      molecular mechanism for apoptotic engagement involves the double cleavage of the
      receptor's intracellular domain, leading to the formation of a proapoptotic
      "killer" fragment (TrkC KF). Here, we show that TrkC KF interacts with Cobra1, a
      putative cofactor of BRCA1, and that Cobra1 is required for TrkC-induced
      apoptosis. We also show that, in the developing chick neural tube, NT-3 silencing
      is associated with neuroepithelial cell death that is rescued by Cobra1
      silencing. Cobra1 shuttles TrkC KF to the mitochondria, where it promotes Bax
      activation, cytochrome c release, and apoptosome-dependent apoptosis. Thus, we
      propose that, in the absence of NT-3, the proteolytic cleavage of TrkC leads to
      the release of a killer fragment that triggers mitochondria-dependent apoptosis
      via the recruitment of Cobra1. 

PMID- 24034696
TI  - The aurora B kinase and the polycomb protein ring1B combine to regulate active
      promoters in quiescent lymphocytes.
AB  - Reversible cellular quiescence is critical for developmental processes in
      metazoan organisms and is characterized by a reduction in cell size and
      transcriptional activity. We show that the Aurora B kinase and the polycomb
      protein Ring1B have essential roles in regulating transcriptionally active genes
      in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active
      promoters in resting B and T cells. Conditional knockout of either protein
      results in reduced transcription and binding of RNA Pol II to promoter regions
      and decreased cell viability. Aurora B phosphorylates histone H3S28 at active
      promoters in resting B cells as well as inhibiting Ring1B-mediated ubiquitination
      of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at
      transcribed genes. Our results identify a mechanism for regulating transcription
      in quiescent cells that has implications for epigenetic regulation of the choice
      between proliferation and quiescence. 

PMID- 24034697
TI  - Inactivation of the novel avian influenza A (H7N9) virus under physical
      conditions or chemical agents treatment.
AB  - BACKGROUND: In the spring of 2013, a novel avian-origin influenza A (H7N9) virus
      in Eastern China emerged causing human infections. Concerns that a new influenza
      pandemic could occur were raised. The potential effect of chemical agents and
      physical conditions on inactivation of the novel avian influenza H7N9 virus had
      not been assessed. METHODS: To determine the inactivation effectiveness of the
      novel avian influenza A (H7N9) virus under various physical conditions and
      chemical treatments, two H7N9 viruses A/Anhui/1/2013 and A/Shanghai/1/2013 were
      treated by varied temperatures, ultraviolet light, varied pHs and different
      disinfectants. The viruses with 107.7 EID50 were exposed to physical conditions
      (temperature, ultraviolet light and pH) or treated with commercial chemical
      agents (Sodium Hypochlorite, Virkon(r)-S, and Ethanol) respectively. After these
      treatments, the viruses were inoculated in SPF embryonated chicken eggs, the
      allantoic fluid was collected after 72-96 hours culture at 35 degrees C and
      tested by haemagglutination assay. RESULTS: Both of the tested viruses could
      tolerate conditions under 56 degrees C for 15 minutes or 60 degrees C for 5
      minutes, but their infectivity was completely lost under 56 degrees C for 30
      minutes, 65 degrees C for 10 minutes, 70 degrees C, 75 degrees C and 100 degrees
      C for 1 minute. It was also observed that the H7N9 viruses lost their infectivity
      totally after exposure of ultraviolet light irradiation for 30 minutes or longer
      time. Additionally, the viruses were completely inactivated at pH less than 2 for
      0.5 hour or pH 3 for 24 hours, however, viruses remained infectious under pH
      treatment of 4-12 for 24 hours. The viruses were totally disinfected when treated
      with Sodium Hypochlorite, Virkon(r)-S and Ethanol at recommended concentrations
      after only 5 minutes. CONCLUSIONS: The novel avian influenza A (H7N9) virus can
      be inactivated under some physical conditions or with chemical treatments, but
      they present high tolerance to moderately acidic or higher alkali conditions. The
      results provided the essential information for public health intervention of
      novel H7N9 avian influenza outbreak.

PMID- 24034698
TI  - The Chinese version of the world health organization quality of life instrument
      older adults module (WHOQOL-OLD): psychometric evaluation.
AB  - BACKGROUND: Under the circumstance of global population aging, the issue on how
      to facilitate the quality of life (QOL) for older people brings us grand
      challenge. On the way to solve this problem, it is inextricable to measure QOL
      for older people accurately at onset. This study is aimed at evaluating the
      reliability and validity of the Chinese version of the World Health Organization
      Quality of Life Instrument-Older Adults Module (WHOQOL-OLD). METHODS: We received
      1005 valid WHOQOL-OLD questionnaires from 1050 respondents who were 60 and older
      by quota sampling method. To calculate the test-retest correlation coefficient we
      re-interviewed 101 participants from the community. Psychometric properties were
      evaluated from the aspect of feasibility, internal consistency reliability, test
      retest reliability, content validity, construct validity and discriminant
      validity. RESULTS: Missing item responses took up 0.0%-2.7% in the scale. The
      WHOQOL-OLD showed satisfactory reliability with Cronbach's Alpha coefficients
      ranging from 0.711 (Social participation) to 0.842 (Sensory ability) for each
      domain. The intra-class correlation coefficients (ICC) presenting test-retest
      reliability were all over 0.7. In Confirmatory Factor Analysis (CFA), Root Mean
      Square Error of Approximation (RMSEA) was 0.084 (a little more than 0.08) and
      comparative fit index (CFI) 0.95 (>0.90) which meant acceptable construct
      validity. There were higher correlation coefficients between items and their
      hypothesized domains than other domains (P < 0.001), indicating good content
      validity. The results of t-test showed good discriminant validity of the WHOQOL
      OLD between the healthy group and the unhealthy group (P < 0.0083). CONCLUSION:
      The Chinese version of WHOQOL-OLD showed good feasibility, reliability and
      validity in this study. However, before it can be used national-widely, further
      research should be conducted in other areas of China.

PMID- 24034699
TI  - Visualization and hypervascularization of the haemorrhoidal plexus in vivo using
      power Doppler imaging transanal ultrasonography and three-dimensional power
      Doppler angiography.
AB  - AIM: The purpose of this study was to demonstrate the distribution of
      haemorrhoidal arteries and the relationship between vascularity and growth of
      haemorrhoids. METHOD: One-hundred and three patients with haemorrhoids were
      studied. Using power Doppler imaging (PDI) transanal ultrasound and three
      dimensional power Doppler angiography (3D-PDA), the course of the arteries
      supplying the haemorrhoids was identified. Measurement of the PDI area was made
      using the cursor to outline the power Doppler signal of the haemorrhoid,
      approximately 1 cm above the dentate line. RESULTS: The haemorrhoidal arteries
      were seen as branches of the superior rectal artery and were detected in 75.7,
      71.8, 68.0 and 62.1% of the 11, 7, 3 and 1 o'clock positions in the lithotomy
      position. The median number of haemorrhoidal arteries significantly increased
      from three to six with progression of the Goligher classification from Grade 1 to
      Grade 4 (P < 0.0001). The PDI areas in Grades 1, 2, 3 and 4 were 0.04 +/- 0.03,
      0.18 +/- 0.07, 0.38 +/- 0.18 and 0.96 +/- 0.32 cm(2) (P < 0.05). CONCLUSION: The
      distribution of haemorrhoidal arteries varies widely in both number and position.
      Using PDI transanal ultrasonography and 3D-PDA it was possible to visualize the
      haemorrhoid plexus and the course of the haemorrhoidal artery in vivo.

PMID- 24034700
TI  - Time course of soluble P-selectin and von Willebrand factor levels in trauma
      patients: a prospective observational study.
AB  - BACKGROUND: Coagulopathy often develops in patients with serious trauma and is
      correlated with the clinical outcome. The contribution of platelet activity and
      endothelial dysfunction to trauma-induced coagulopathy remain to be defined. The
      purpose of this study was to investigate the time courses of soluble P-selectin
      (sPsel, an index of platelet activation) and von Willebrand factor (VWF, an index
      of endothelial dysfunction) in trauma patients and elucidate their relationship
      to coagulation parameter levels, the presence of coagulopathy, and patient
      outcome. METHODS: This prospective observational study, which took place in a
      university hospital intensive care unit (ICU), included 82 severely injured
      trauma patients. The sPsel, VWF antigen, protein C, and factor VII levels were
      measured and routine coagulation tests were performed upon admission to ICU and
      daily within the first week. The 30-day mortality rate was also determined.
      RESULTS: Thirty-seven (45.1%) patients developed coagulopathy upon admission to
      the ICU, and the 30-day mortality rate was 20.7% (n = 17). Both the admission
      sPsel and VWF levels were lower in patients with coagulopathy than in those
      without (p < 0.05) and were significantly correlated with the protein C and
      factor VII levels, respectively (all p < 0.05). The VWF levels were lower during
      the first 3 days and higher on day 7 after admission in nonsurvivors than in
      survivors (all p < 0.05). No significant differences in sPsel levels were found
      between nonsurvivors and survivors on each day during the first week. CONCLUSION:
      In severely injured trauma patients in the ICU, lower levels of sPsel and VWF on
      admission were associated with the presence of coagulopathy and might not predict
      a better outcome. An increase in the VWF level at the end of the first week after
      admission to ICU was associated with increased 30-day mortality.

PMID- 24034701
TI  - Respiratory viral infections and effects of meteorological parameters and air
      pollution in adults with respiratory symptoms admitted to the emergency room.
AB  - BACKGROUND: Respiratory viral infections (RVIs) are the most common causes of
      respiratory infections. The prevalence of respiratory viruses in adults is
      underestimated. Meteorological variations and air pollution are likely to play a
      role in these infections. OBJECTIVES: The objectives of this study were to
      determine the number of emergency visits for influenza-like illness (ILI) and
      severe acute respiratory infection (SARI) and to evaluate the association between
      ILI/SARI, RVI prevalence, and meteorological factors/air pollution, in the city
      of Porto Alegre, Brazil, from November 2008 to October 2010. METHODS: Eleven
      thousand nine hundred and fifty-three hospitalizations (adults and children) for
      respiratory symptoms were correlated with meteorological parameters and air
      pollutants. In a subset of adults, nasopharyngeal aspirates were collected and
      analyzed through IFI test. The data were analyzed using time-series analysis.
      RESULTS: Influenza-like illness and SARI were diagnosed in 3698 (30.9%) and 2063
      (17.7%) patients, respectively. Thirty-seven (9.0%) samples were positive by IFI
      and 93 of 410 (22.7%) were IFI and/or PCR positive. In a multivariate logistic
      regression model, IFI positivity was statistically associated with absolute
      humidity, use of air conditioning, and presence of mold in home. Sunshine
      duration was significantly associated with the frequency of ILI cases. For SARI
      cases, the variables mean temperature, sunshine duration, relative humidity, and
      mean concentration of pollutants were singnificant. CONCLUSIONS: At least 22% of
      infections in adult patients admitted to ER with respiratory complaints were
      caused by RVI. The correlations among meteorological variables, air pollution,
      ILI/SARI cases, and respiratory viruses demonstrated the relevance of climate
      factors as significant underlying contributors to the prevalence of RVI.

PMID- 24034703
TI  - Organ donor shift.

PMID- 24034702
TI  - Efficient disruption of Zebrafish genes using a Gal4-containing gene trap.
AB  - BACKGROUND: External development and optical transparency of embryos make
      zebrafish exceptionally suitable for in vivo insertional mutagenesis using
      fluorescent proteins to visualize expression patterns of mutated genes. Recently
      developed Gene Breaking Transposon (GBT) vectors greatly improve the fidelity and
      mutagenicity of transposon-based gene trap vectors. RESULTS: We constructed and
      tested a bipartite GBT vector with Gal4-VP16 as the primary gene trap reporter.
      Our vector also contains a UAS:eGFP cassette for direct detection of gene trap
      events by fluorescence. To confirm gene trap events, we generated a UAS:mRFP
      tester line. We screened 270 potential founders and established 41 gene trap
      lines. Three of our gene trap alleles display homozygous lethal phenotypes
      ranging from embryonic to late larval: nsf( tpl6), atp1a3a(tpl10) and flr(tpl19).
      Our gene trap cassette is flanked by direct loxP sites, which enabled us to
      successfully revert nsf( tpl6), atp1a3a(tpl10) and flr(tpl19) gene trap alleles
      by injection of Cre mRNA. The UAS:eGFP cassette is flanked by direct FRT sites.
      It can be readily removed by injection of Flp mRNA for use of our gene trap
      alleles with other tissue-specific GFP-marked lines. The Gal4-VP16 component of
      our vector provides two important advantages over other GBT vectors. The first is
      increased sensitivity, which enabled us to detect previously unnoticed expression
      of nsf in the pancreas. The second advantage is that all our gene trap lines,
      including integrations into non-essential genes, can be used as highly specific
      Gal4 drivers for expression of other transgenes under the control of Gal4 UAS.
      CONCLUSIONS: The Gal4-containing bipartite Gene Breaking Transposon vector
      presented here retains high specificity for integrations into genes, high
      mutagenicity and revertibility by Cre. These features, together with utility as
      highly specific Gal4 drivers, make gene trap mutants presented here especially
      useful to the research community.

PMID- 24034705
TI  - Activating killers by stimulating RAGE.

PMID- 24034706
TI  - Laparoscopic live donor hepatectomy: random mutation or stepwise evolution?

PMID- 24034707
TI  - Rapamycin augments human DC IL-12p70 and IL-27 secretion to promote allogeneic
      Type 1 polarization modulated by NK cells.
AB  - Mammalian target of rapamycin kinase inhibitor (mTORi) rapamycin (RAPA) use in
      transplantation can lead to inflammatory complications in some patients. Our goal
      was to better understand how mTORi-exposed human monocyte-derived dendritic cells
      (DC) stimulated with pro-inflammatory cytokines shape T cell allo-immunity. RAPA
      conditioned-DC (RAPA-DC) displayed a more immature phenotype than untreated,
      control (CTRL)-DC. However, subsequent exposure of RAPA-DC to an inflammatory
      cytokine cocktail (ICC) plus IFN-gamma induced a mature Type-1 promoting
      phenotype, consisting of elevated HLA-DR and co-stimulatory molecules, augmented
      IL-12p70 and IL-27 production, but decreased IL-10 secretion compared to CTRL-DC.
      Co-culture of mature (m)RAPA-DC with allogeneic peripheral blood mononuclear
      cells resulted in significantly increased Type-1 (IFN-gamma) responses by T
      cells. Moreover, NK cells acted as innate modulators that conveyed activating
      cell-to-cell contact signals in addition to helper (IFN-gamma) and/or regulatory
      (IL-10) soluble cytokines. We conclude that production of IL12-p70, IL-27 and low
      IL-10 by RAPA-DC allowed us to elucidate how these cytokines as well as NK-DC
      interaction shapes T cell allo-immunity. Thus, lack of inhibitory NK cell
      function during allo-specific T cell activation by human ICC + IFN-gamma
      stimulated RAPA-DC may represent an unwanted effector mechanism that may underlie
      RAPA-induced inflammatory events in transplant patients undergoing microbial
      infection or allograft rejection.

PMID- 24034709
TI  - Totally laparoscopic full left hepatectomy for living donor liver transplantation
      in adolescents and adults.
AB  - In recent years different minimal access strategies have been designed in order
      to perform living donor liver surgery for adult recipients with less morbidity.
      Techniques involve shortening the length of the incision with or without previous
      laparoscopic mobilization of the liver. Herein we present two cases of totally
      laparoscopic living donor left hepatectomy, with and without removal of the
      middle hepatic vein, respectively. We describe in detail the anatomical and
      technical aspects of the procedure focusing on relevant points to enhance safety.

PMID- 24034711
TI  - An uncommon neurologic complication following orthotopic liver transplantation.

PMID- 24034708
TI  - Prominent impact of community risk factors on kidney transplant candidate
      processes and outcomes.
AB  - Numerous factors impact patients' health beyond traditional clinical
      characteristics. We evaluated the association of risk factors in kidney
      transplant patients' communities with outcomes prior to transplantation. The
      primary exposure variable was a community risk score (range 0-40) derived from
      multiple databases and defined by factors including prevalence of comorbidities,
      access and quality of healthcare, self-reported physical and mental health and
      socioeconomic status for each U.S. county. We merged data with the Scientific
      Registry of Transplant Recipients (SRTR) and utilized risk-adjusted models to
      evaluate effects of community risk for adult candidates listed 2004-2010 (n = 209
      198). Patients in highest risk communities were associated with increased
      mortality (adjusted hazard ratio [AHR] = 1.22, 1.16-1.28), decreased likelihood
      of living donor transplantation (adjusted odds ratio [AOR] = 0.90, 0.85-0.94),
      increased waitlist removal for health deterioration (AHR = 1.36, 1.22-1.51),
      decreased likelihood of preemptive listing (AOR = 0.85, 0.81-0.88), increased
      likelihood of inactive listing (AOR = 1.49, 1.43-1.55) and increased likelihood
      of listing for expanded criteria donor kidneys (AHR = 1.19, 1.15-1.24).
      Associations persisted with adjustment for rural-urban location; furthermore the
      independent effects of rural-urban location were largely eliminated with
      adjustment for community risk. Average community risk varied widely by region and
      transplant center (median = 21, range 5-37). Community risks are powerful factors
      associated with processes of care and outcomes for transplant candidates and may
      be important considerations for developing effective interventions and measuring
      quality of care of transplant centers.

PMID- 24034712
TI  - Patients with persistent pain after breast cancer treatment show enhanced alpha
      activity in spontaneous EEG.
AB  - OBJECTIVE: The aim of the present study was to investigate whether patients with
      persistent pain after breast cancer treatment show an enhanced and slowed
      dominant alpha activity in their electroencephalogram (EEG) recorded during rest
      in comparison with patients that also had undergone breast cancer treatment but
      do not have pain. METHODS: The spontaneous EEG was recorded during rest and
      before painful stimulation of the calf and analyzed with spectral analysis (Fast
      Fourier Transformation). Outcome measures, i.e., alpha indices (center of gravity
      and overall amplitude), were statistically tested between patients with and
      without persistent pain. RESULTS: In comparison with patients without pain,
      patients with persistent pain after breast cancer treatment show more alpha
      activity in their spontaneous EEG observed from parietal-occipital brain regions.
      CONCLUSION: Persistent pain after breast cancer treatment affects spontaneous
      brain activity, which might influence cognitive functioning.

PMID- 24034713
TI  - Oxytocinergic manipulations in corticolimbic circuit differentially affect fear
      acquisition and extinction.
AB  - The oxytocinergic system promotes social behavior and reduces anxiety. The
      significant roles and functional interactions of the medial prefrontal cortex and
      the amygdala in the regulation of fear provide a unique experimental setting to
      examine the effects of oxytocin on extinction of fear. In this study we
      manipulated the oxytocin system at different time points in either the
      infralimbic region of the medial prefrontal cortex (IL-mPFC), the basolateral
      amygadala (BLA) or in the central amygdala (CeA). Manipulations of the oxytocin
      following retrieval of fear in the IL-mPFC resulted in facilitation of subsequent
      extinction. In contrast, in the BLA, manipulating the oxytocinergic system after
      the retrieval of fear was associated with contrasting effects; whereas the
      microinjection of exogenous synthetic oxytocin was associated with impaired
      extinction, the microinfusion of WAY-267474 facilitated extinction. In contrast,
      intra-BLA microinfusion of the selective agonist TGOT did not affect freezing.
      Oxytocin manipulations in the CeA had no effect on subsequent extinction.
      Contrasting effects were also found when the drugs were injected before
      conditioning. Whereas oxytocin manipulations in the BLA enhanced fear and
      impaired extinction, in the CeA the microinfusion of the selective agonists (WAY
      267474 and TGOT), but not synthetic oxytocin, resulted in reduced freezing
      levels. These results show that in the rat, the oxytocinergic system
      differentially regulated fear and extinction in region and temporal-dependent
      manners and further join data to show that contrary to the prevailing belief that
      oxytocin is solely involved in reducing fear, oxytocin can also act as an
      enhancer of fear responses. 

PMID- 24034714
TI  - Testosterone and temperament traits in men: Longitudinal analysis.
AB  - Testosterone is the main male hormone that has been associated with various
      behavioral traits in humans and other animals. We investigated whether levels of
      total testosterone, free testosterone, and sex hormone binding globulin were
      associated with temperament traits in a population-based sample of Finnish men at
      two measurement times taken 6 years apart (n=686 in year 2001, n=727 in year
      2007). Temperament was assessed using the Temperament and Character Inventory
      that consists of four temperament traits: novelty seeking, harm avoidance, reward
      dependence, and persistence. Higher levels of total and free testosterone were
      associated with higher novelty seeking (standardized B=0.103, p<0.001). This
      association was also observed in a longitudinal within-person analysis (B=0.084,
      p=0.008), suggesting that the association is not confounded by stable between
      individual differences in other characteristics. Within-individual variation in
      total testosterone was associated with higher reward dependence, and higher
      levels of free testosterone were marginally associated with higher reward
      dependence. Reward dependence reflects the importance of social rewards to an
      individual. These results provide additional evidence for the stable and time
      varying associations between testosterone and temperament in humans. 

PMID- 24034715
TI  - Leucine-enkephalin-like immunoreactivity is localized in luteinizing hormone
      producing cells in the axolotl (Ambystoma mexicanum) pituitary.
AB  - In this study, we used immunohistochemical techniques to determine the cell type
      of leucine-enkephalin (Leu-ENK)-immunoreactive cells in the axolotl (Ambystoma
      mexicanum) pituitary. Immunoreactive cells were scattered throughout the pars
      distalis except for the dorso-caudal portion. These cells were immuno-positive
      for luteinizing hormone (LH), but they were immuno-negative for
      adrenocorticotrophic, growth, and thyroid-stimulating hormones, as well as
      prolactin. Immunoelectron microscopy demonstrated that Leu-ENK-like substance and
      LH co-localized within the same secretory granules. Leu-ENK secreted from
      gonadotrophs may participate in LH secretion in an autocrine fashion, and/or may
      participate in the release of sex steroids together with LH. 

PMID- 24034716
TI  - The efficacy of chlorhexidine dentifrice or gel on plaque, clinical parameters of
      gingival inflammation and tooth discoloration: a systematic review.
AB  - AIM: Based on the existing scientific literature, the effect of chlorhexidine
      (CHX) dentifrice/gel as compared to a regular or placebo dentifrice/gel is
      established in healthy adults on the primary outcome parameters of plaque and
      gingivitis scores. As secondary parameter, tooth surface discoloration was
      evaluated as a side effect. MATERIALS AND METHODS: MEDLINE, EMBASE and Cochrane
      Central Register of Controlled Trials were searched up to July 2013 to identify
      eligible studies. Included were (randomized) controlled clinical trials,
      regarding self-performed brushing by adults without periodontitis with a minimum
      duration of 4 weeks. RESULTS: Independent screening of 389 unique titles and
      abstracts resulted in 16 comparisons. Of these, nine evaluated CHX dentifrice
      (0.4-1.0%) and 7 CHX gel (0.2-2.0%). It was not possible to perform a meta
      analysis; therefore, a descriptive analysis was carried out. Regarding plaque
      score reduction, the majority of the experiments using a CHX dentifrice provided
      a significant positive effect. All studies assessing gingival bleeding as
      parameter for gingivitis observed a significant reduction in favour of CHX
      dentifrice over placebo dentifrice. Tooth surface discoloration was more
      pronounced with CHX dentifrice. The combined data concerning parameters of
      interest for CHX gel compared with a placebo did not show a trend towards a
      beneficial effect on plaque and bleeding scores. CONCLUSIONS: Within the
      limitations of this analysis, it may be concluded that toothbrushing with a CHX
      gel does not provide conclusive evidence. Brushing with a CHX dentifrice can be
      effective with regard to the control of plaque and gingivitis. Tooth surface
      discoloration was observed as side effect, which potentially can have a negative
      impact on patients' compliance.

PMID- 24034717
TI  - Food products qualifying for and carrying front-of-pack symbols: a cross
      sectional study examining a manufacturer led and a non-profit organization led
      program.
AB  - BACKGROUND: Concern has been raised that the coexistence of multiple front-of
      pack (FOP) nutrition rating systems in a marketplace may mislead consumers into
      believing that a specific food with a FOP is 'healthier' than foods without the
      symbol. Eleven summary indicator FOP systems are in use in Canada, including one
      non-profit developed system, the Heart and Stroke Foundation's Health CheckTM,
      and ten manufacturer-developed systems, like Kraft's Sensible SolutionsTM. This
      study evaluated FOP's potential to mislead consumers by comparing the number of
      products qualifying to carry a given FOP symbol to the number of products that
      actually carry the symbol. METHODS: The nutritional criteria for the Health
      CheckTM and the Sensible SolutionsTM systems were applied to a 2010-2011 Canadian
      national database of packaged food products. The proportion of foods qualifying
      for a given FOP system was compared to the proportion carrying the symbol using
      McNemar's test. RESULTS: Criteria were available to categorize 7503 and 3009 of
      the 10,487 foods in the database under Health CheckTM and Sensible SolutionsTM,
      respectively. Overall 45% of the foods belonging to a Health CheckTM category
      qualified for Health Check'sTM symbol, while only 7.5% of the foods carried the
      symbol. Up to 79.1% of the foods belonging to a Sensible SolutionsTM, category
      qualified for Sensible Solutions'sTM symbol while only 4.1% of the foods carried
      the symbol. The level of agreement between products qualifying for and carrying
      FOP systems was poor to moderate in the majority of food categories for both
      systems. More than 75% of the products in 24 of the 85 Health CheckTM
      subcategories and 9 of 11 Sensible SolutionTM categories/subcategories qualified
      for their respective symbols based on their nutritional composition. CONCLUSIONS:
      FOP systems as they are currently applied are not, in most instances, a useful
      guide to identifying healthier food products in the supermarket as many more
      products qualify for these systems than the number of products actually
      displaying these symbols on FOP, and the level of agreement between qualifying
      and carrying products is poor to moderate. The adoption of a single, standardized
      FOP system would assure consumers that all products meeting certain nutritional
      standards are designated by the symbol.

PMID- 24034718
TI  - Maternal and health care determinants of preconceptional use of folic acid
      supplementation in France: results from the 2010 National Perinatal Survey.
AB  - OBJECTIVES: To estimate the national prevalence and analyse the factors
      associated with preconceptional folic acid supplementation, including maternal
      sociodemographic characteristics, region of residence, birth control use and
      chronic diseases requiring medical care before conception. DESIGN: Cross
      sectional population-based study. SETTING: All maternity units in France.
      POPULATION: A nationally representative sample of women giving birth in 2010 (n =
      12,646). METHODS: Data came from mothers' interviews 2-3 days after delivery.
      Statistical analyses included multivariable logistic regressions. MAIN OUTCOME
      MEASURE: Folic acid supplementation starting at least 1 month before conception.
      RESULTS: 14.8% (95% confidence interval [95% CI] 14.2-15.4) of women used folic
      acid before pregnancy; this percentage varied from 10.4% to 18.7% across regions.
      Supplementation was more frequent in primiparae, French citizens, women with
      higher educational levels and those needing medical monitoring or treatment
      before conception. Women who stopped contraception to become pregnant (75% of our
      population) used folic acid more often (intrauterine device or implant: 19%,
      pill: 17%, other methods which did not need medical monitoring: 17%) than other
      women (7%). The adjusted odds ratios were 3.3 (95% CI 2.6-4.3) for intrauterine
      device and implant, 2.2 (95% CI 1.8-2.6) for pill and 1.9 (95% CI 1.5-2.4) for
      other methods, compared with women who did not use birth control. CONCLUSION: The
      absence of preconceptional folic acid supplementation for most women, even those
      needing consultations with healthcare professionals before pregnancy, shows that
      campaigns to promote folic acid supplementation should address not only women but
      also healthcare professionals involved in birth control and obstetric care before
      pregnancy.

PMID- 24034719
TI  - Phylogeny and phenotypes of clinical and environmental Shiga toxin-producing
      Escherichia coli O174.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC) of serogroup O174 are human
      pathogenic intimin gene (eae)-negative STEC. To facilitate diagnosis and
      subtyping, we genotypically and phenotypically characterized 25 STEC O174
      isolates from humans with different clinical outcomes and from animals and the
      environment. fliC genotyping resulted in four different genotypes (fliCH2 : n =
      5; fliCH8 : n = 8; fliCH21 : n = 11; fliCH46 : n = 1). Twenty-three strains were
      motile expressing the corresponding H antigen; two non-motile isolates possessed
      fliCH8 . The stx genotypes and non-stx virulence loci, including toxins, serine
      proteases and adhesins correlated well with serotypes but showed no differences
      with respect to the isolates' origins. Multilocus sequence typing identified
      seven sequence types that correlated with serotypes. Core gene typing further
      specified the four serotypes, including a previously unknown O174:H46
      combination, and revealed distant relationships of the different serotypes within
      serogroup O174 and in relation to other haemolytic uremic syndrome (HUS)
      associated STEC. Only serotype O174:H21 was associated with HUS. Differences in
      virulence factors and in the adherence capacity of STEC O174 corroborated this
      separation into four distinct groups. Our study provides a basis for O174
      subtyping, unravels considerable genotypic and phenotypic heterogeneity and sheds
      light to potential environmental and animal reservoirs.

PMID- 24034720
TI  - A new method for gridding DNA microarrays.
AB  - In this paper, a new methodological scheme for the gridding of DNA microarrays is
      proposed. The scheme composes of a series of processes applied sequentially. Each
      DNA microarray image is pre-processed to remove any noise and the center of each
      spot is detected using a template matching algorithm. Then, an initial gridding
      is automatically placed on the DNA microarray image by 'building' rectangular
      pyramids around the detected spots' centers. The gridlines "move" between the
      pyramids, horizontally and vertically, forming this initial grid. Furthermore, a
      refinement process is applied composing of a five-step approach in order to
      correct gridding imperfections caused by its initial placement, both in non-spot
      cases and in more than one spot enclosure cases. The proposed gridding scheme is
      applied on DNA microarray images under known transformations and on real-world
      DNA data. Its performance is compared against the projection pursuit method,
      which is often used due to its speed and simplicity, as well as against a state
      of-the-art method, the Optimal Multi-level Thresholding Gridding (OMTG).
      According to the obtained results, the proposed gridding scheme outperforms both
      methods, qualitatively and quantitatively.

PMID- 24034721
TI  - Classification of diffusion tensor images for the early detection of Alzheimer's
      disease.
AB  - Early detection of Alzheimer's disease (AD) is important since treatments are
      more efficacious when used at the beginning of the disease. Despite significant
      advances in diagnostic methods for AD, there is no single diagnostic method for
      AD with high accuracy. We developed a support vector machine (SVM) model that
      classifies mild cognitive impairment (MCI) and normal control subjects using
      probabilistic tractography and tract-based spatial statistics of diffusion tensor
      imaging (DTI) data. MCI is an intermediate state between normal aging and AD, so
      finding MCI is important for an early diagnosis of AD. The key features of DTI
      data we identified through extensive analysis include the fractional anisotropy
      (FA) values of selected voxels, their average FA value, and the volume of fiber
      pathways from a pre-defined seed region. In particular, the volume of the fiber
      pathways to thalamus is the most powerful single feature in classifying MCI and
      normal subjects regardless of the age of the subjects. The best performance
      achieved by the SVM model in a 10-fold cross validation and in independent
      testing was sensitivity of 100%, specificity of 100% and accuracy of 100%.

PMID- 24034722
TI  - Heating characteristics of antenna arrays used in microwave ablation: A
      theoretical parametric study.
AB  - A numerical study of the performance of antenna arrays used in microwave ablation
      (MWA) is carried out. Double-slot coaxial antennas in triangular and square
      configurations are studied. Clinical (healthy vs. malignant) and experimental (in
      vs. ex vivo) scenarios for hepatic cancer treatment are modeled, and further
      application in bone and lung tissue is examined. It is found that triangular
      arrays can create spherical ablation zones, while square configurations result in
      flatter ones. Thresholds in power and application times for creating continuous
      ablation zones are calculated, and the characteristics of the latter are
      quantified.

PMID- 24034723
TI  - Predicting cardiac autonomic neuropathy category for diabetic data with missing
      values.
AB  - Cardiovascular autonomic neuropathy (CAN) is a serious and well known
      complication of diabetes. Previous articles circumvented the problem of missing
      values in CAN data by deleting all records and fields with missing values and
      applying classifiers trained on different sets of features that were complete.
      Most of them also added alternative features to compensate for the deleted ones.
      Here we introduce and investigate a new method for classifying CAN data with
      missing values. In contrast to all previous papers, our new method does not
      delete attributes with missing values, does not use classifiers, and does not add
      features. Instead it is based on regression and meta-regression combined with the
      Ewing formula for identifying the classes of CAN. This is the first article using
      the Ewing formula and regression to classify CAN. We carried out extensive
      experiments to determine the best combination of regression and meta-regression
      techniques for classifying CAN data with missing values. The best outcomes have
      been obtained by the additive regression meta-learner based on M5Rules and
      combined with the Ewing formula. It has achieved the best accuracy of 99.78% for
      two classes of CAN, and 98.98% for three classes of CAN. These outcomes are
      substantially better than previous results obtained in the literature by deleting
      all missing attributes and applying traditional classifiers to different sets of
      features without regression. Another advantage of our method is that it does not
      require practitioners to perform more tests collecting additional alternative
      features.

PMID- 24034724
TI  - Analysis of the structure of calpain-10 and its interaction with the protease
      inhibitor SNJ-1715.
AB  - Calpain-10 (CAPN10) is a cysteine protease that is activated by intracellular
      calcium (Ca(2+)) and known to be involved in diseases such as cancer, heart
      attack, and stroke. A role for the CAPN10 gene in diabetes mellitus type II was
      recently identified. Hyper activation of the enzyme initiates a series of
      destructive cycles that can cause irreversible damage to cells. The development
      of inhibitors may be useful as therapeutic agents for a number of
      calpainopathies. In this paper, we have used the homology modelling technique to
      determine the 3D structure of calpain-10 from Homo sapiens. The model of calpain
      10 obtained by homology modelling suggests that its active site is conserved
      among family members and the main interactions are similar to those observed for
      MU-calpain. Structural analysis revealed that there are small differences in the
      charge distribution and molecular surface of the enzyme. These differences are
      probably less dependent on calcium for calpain-10 than they are for MU-calpain.
      In addition, the ion pair Cys(-)/His(+) formation was observed using of Molecular
      Dynamics (MD) simulations that were based upon hybrid quantum
      mechanical/molecular mechanical (QM/MM) approaches. Finally, the binding of the
      SNJ-1715 inhibitor to calpain-10 was investigated in order to further understand
      the mechanism of inhibition of calpain-10 by this inhibitor at the molecular
      level.

PMID- 24034725
TI  - Fully automated computer-aided volume estimation system for thyroid planar
      scintigraphy.
AB  - Patient-specific dosimetry calculations are often performed for radioiodine
      therapy in patients with Graves' hyperthyroidism. The radioiodine doses are
      typically calculated to deliver the desired amount of radiation based on gland
      size and radioactive iodine uptake. Thus the estimation of thyroid gland volume
      is of great importance for radioiodine therapy. In clinical practice, thyroid
      volume determinations are usually performed with ultrasonography (US) or with
      planar scintigraphy (PS). In traditional planar scintigraphic studies, the
      thyroid boundary is estimated using a fixed threshold value if the shape of the
      thyroid is well-defined or a manually drawn region of interest (ROI) if the
      thyroid shape is irregular. The thyroid volume is then calculated based on the
      area thus determined. Delineating the thyroid area on a planar scintigram is not
      easy when applying a fixed threshold value. Moreover, hand-drawn ROIs are time
      consuming, tedious, and highly operator-dependent. In this study, for a PS image,
      a fully automated thyroid volume estimation system mainly consisting of four
      steps, i.e. preprocessing, image contrast enhancement, image segmentation, and
      automated ROI finding, was proposed to obtain the maximum height and area of each
      thyroid lobe, and thus calculate the thyroid volume using either Himanka
      Larsson's formula or Allen-Goodwin's formula. A set of 40 Graves's disease
      patients regarded as training set were used to determine empirically some
      parameters operated in the system. A set of 30 Graves's disease patients being
      independent of the training set, regarded as test set for thyroid volume
      measurements were used for comparisons and performance analyses. In this study,
      the US was adopted as a standard reference. The statistical analyses were
      performed with bias, precision, and relative differences. The results of thyroid
      volume estimation from the proposed approach correlated well with those from US,
      and the statistical performance analyses showed good agreement between them. In
      comparison, our automated approach with Allen-Goodwin's formula had not only good
      correlation with US (R(2)=0.99) but also the best bias (0.8), precision (+/-2.32
      ml), and low relative differences (2.2 +/- 6.1%). It is expected that this
      automated computer-assisted approach can help physicians in the determination of
      patient-specific administered activities for treatment of thyroid disease.

PMID- 24034726
TI  - Image-based computational hemodynamics evaluation of atherosclerotic carotid
      bifurcation models.
AB  - Widely accepted treatment for carotid artery stenosis includes stenting as well
      as carotid endoarterectomy (CEA), despite complications associated with distal
      embolism. Therefore pre-screening for evaluating the extent of a stenosis is
      critically important before undertaking surgical procedures. This study presents
      and evaluates the feasibility of implementing a virtual computational
      hemodynamics platform for clinical use to determine the severity of a stenosis
      and give guidance for surgical decision making. The virtual platform incorporates
      high-resolution three-dimensional angiography results with Computational Fluid
      Dynamics modeling to determine clinically related indicators. This includes wall
      shear stress (WSS), the spatial and temporal hemodynamic changes of blood flow
      within patient-specific carotid bifurcations, pressure drop coefficient, and
      severity stratification. The turn-around time for each computational modeling
      stage was examined which showed that the total time cost is practical and the
      proposed hemodynamics evaluation platform is reasonably efficient for clinical
      diagnosis. Furthermore the virtual platform may be used to detect the hemodynamic
      consequence of atherogenesis, which can then be addressed and quantified based on
      the distribution of WSS related flow indicators on the abnormal luminal
      fractions. Additional functional evidence and data can be used by the overseeing
      physician to enrich and complement the anatomical information for more in-depth
      evaluation of stenosis in a reasonable time duration.

PMID- 24034727
TI  - ICP: A novel approach to predict prognosis of prostate cancer with inner-class
      clustering of gene expression data.
AB  - Prostate cancer has heterogeneous characteristics. For that reason, even if
      tumors appear histologically similar to each other, there are many cases in which
      they are actually different, based on their gene expression levels. A single
      tumor may have multiple expression levels with both high-risk cancer genes and
      low-risk cancer genes. We can produce more useful models for stratifying prostate
      cancers into high-risk cancer and low-risk cancer categories by considering the
      range in each class through inner-class clustering. In this paper, we attempt to
      classify cancers into high-risk (aggressive) prostate cancer and low-risk (non
      aggressive) prostate cancer using ICP (Inner-class Clustering and Prediction).
      Our model classified more efficiently than the models of the algorithms used for
      comparison. After discovering a number of genes linked to prostate cancer from
      the gene pairs used in our classification, we discovered that the proposed method
      can be used to find new unknown genes and gene pairs which distinguish between
      high-risk cancer and low-risk cancer.

PMID- 24034728
TI  - Binding of intronic miRNAs to the mRNAs of host genes encoding intronic miRNAs
      and proteins that participate in tumourigenesis.
AB  - In this study, we examined 615 host genes encoding 915 in-miRNAs as possible
      targets for interactions with all in-miRNAs. Host genes whose proteins are
      involved in esophageal, gastric, small bowel, colorectal, and breast cancer
      development were studied. Unique in-miRNA binding sites with a significance of
      p<0.0005 were found in the 5'UTRs, CDSs, and 3'UTRs of the host genes encoding
      proteins that are key participants in tumourigenesis. These data shed light on
      the interactions between miRNAs and mRNAs and on the role of candidate proteins
      in cancer. Therefore, our findings have potential application in the development
      of diagnostic and treatment methods.

PMID- 24034729
TI  - GPU-accelerated 3D mipmap for real-time visualization of ultrasound volume data.
AB  - Ultrasound volume rendering is an efficient method for visualizing the shape of
      fetuses in obstetrics and gynecology. However, in order to obtain high-quality
      ultrasound volume rendering, noise removal and coordinates conversion are
      essential prerequisites. Ultrasound data needs to undergo a noise filtering
      process; otherwise, artifacts and speckle noise cause quality degradation in the
      final images. Several two-dimensional (2D) noise filtering methods have been used
      to reduce this noise. However, these 2D filtering methods ignore relevant
      information in-between adjacent 2D-scanned images. Although three-dimensional
      (3D) noise filtering methods are used, they require more processing time than 2D
      based methods. In addition, the sampling position in the ultrasonic volume
      rendering process has to be transformed between conical ultrasound coordinates
      and Cartesian coordinates. We propose a 3D-mipmap-based noise reduction method
      that uses graphics hardware, as a typical 3D mipmap requires less time to be
      generated and less storage capacity. In our method, we compare the density values
      of the corresponding points on consecutive mipmap levels and find the noise area
      using the difference in the density values. We also provide a noise detector for
      adaptively selecting the mipmap level using the difference of two mipmap levels.
      Our method can visualize 3D ultrasound data in real time with 3D noise filtering.

PMID- 24034730
TI  - Modeling stroke rehabilitation processes using the Unified Modeling Language
      (UML).
AB  - In organising and providing rehabilitation procedures for stroke patients, the
      usual need for many refinements makes it inappropriate to attempt rigid
      standardisation, but greater detail is required concerning workflow. The aim of
      this study was to build a model of the post-stroke rehabilitation process. The
      model, implemented in the Unified Modeling Language, was grounded on
      international guidelines and refined following the clinical pathway adopted at
      local level by a specialized rehabilitation centre. The model describes the
      organisation of the rehabilitation delivery and it facilitates the monitoring of
      recovery during the process. Indeed, a system software was developed and tested
      to support clinicians in the digital administration of clinical scales. The model
      flexibility assures easy updating after process evolution.

PMID- 24034731
TI  - A computerized decision support system to predict the variations in the cerebral
      blood flow of mechanically ventilated infants.
AB  - A computerized decision support system is described to predict the changes in the
      cerebral blood flow (CBF) of mechanically ventilated infants in response to
      different ventilatory settings. A CBF controller was developed and combined with
      a mathematical model of the infant's respiratory system to simulate the effects
      of ventilatory settings on the infant's CBF. The performance of the system was
      examined under various ventilatory treatments and the results were compared with
      available experimental data. The comparisons showed good agreement between the
      simulation results and experimental data for preterm infants. These included the
      results obtained under conditions of hypoventilation, hyperventilation, hypoxia,
      and hyperoxia. The presented decision support system has the potential to be used
      as an aide to the intensivist in choosing appropriate ventilation treatments for
      infants to prevent the untoward consequences of hazardous changes in CBF in
      mechanically ventilated infants such as hypoxic-ischemic brain injuries.

PMID- 24034732
TI  - Multi-level basis selection of wavelet packet decomposition tree for heart sound
      classification.
AB  - Wavelet packet transform decomposes a signal into a set of orthonormal bases
      (nodes) and provides opportunities to select an appropriate set of these bases
      for feature extraction. In this paper, multi-level basis selection (MLBS) is
      proposed to preserve the most informative bases of a wavelet packet decomposition
      tree through removing less informative bases by applying three exclusion
      criteria: frequency range, noise frequency, and energy threshold. MLBS achieved
      an accuracy of 97.56% for classifying normal heart sound, aortic stenosis, mitral
      regurgitation, and aortic regurgitation. MLBS is a promising basis selection to
      be suggested for signals with a small range of frequencies. 

PMID- 24034733
TI  - A pattern-oriented specification of gene network inference processes.
AB  - Patterns have been widely used in Computer Science. A pattern describes a generic
      solution to an existing problem in a more readable and accessible form. A pattern
      oriented process specification consists of a generic and abstract description of
      a process. This paper presents a pattern-oriented specification of a genetic
      regulatory network inference process performed from microarray data and prior
      biological knowledge. The proposed specification was conceived based on prior
      work on gene inference networks. The adequacy of the proposed solution was then
      evaluated with respect to modern tendencies of the genes network inference
      literature.

PMID- 24034734
TI  - A home daily activity simulation model for the evaluation of lifestyle monitoring
      systems.
AB  - Lifestyle monitoring (LM) technology is part of a new generation of telecare
      which aims to observe the daily activities of older or vulnerable individuals and
      determine if a medical or care intervention would be beneficial. The development
      and validation of new LM systems should ideally involve extensive trials with
      users in real conditions. Unfortunately, effective user trials are very
      challenging, generally limited in scope and costly. In this paper, a simulator is
      proposed that can serve to generate synthetic data of daily activity which can
      then be used as a tool for the validation and development of LM systems. The most
      challenging part of the simulator is to replicate people's behaviour. In the
      paper, a novel model of daily activity simulation is proposed. Such daily
      activities are dependent on a number of external factors that control the need or
      desire to perform the activity. The proposed simulator aims to reproduce
      behaviour such that the probability of performing an activity increases until the
      need is fulfilled. It is possible to parameterise the behavioural model according
      to a set of features representing a particular individual. The simulator
      parameters have been populated using real world experiments through hardware
      testing and data collection with older people. Experimental verification that the
      desired features are reasonably reproduced by the simulator is provided.

PMID- 24034735
TI  - Exploring correlations in gene expression microarray data for maximum predictive
      minimum redundancy biomarker selection and classification.
AB  - An important issue in the analysis of gene expression microarray data is
      concerned with the extraction of valuable genetic interactions from high
      dimensional data sets containing gene expression levels collected for a small
      sample of assays. Past and ongoing research efforts have been focused on
      biomarker selection for phenotype classification. Usually, many genes convey
      useless information for classifying the outcome and should be removed from the
      analysis; on the other hand, some of them may be highly correlated, which reveals
      the presence of redundant expressed information. In this paper we propose a
      method for the selection of highly predictive genes having a low redundancy in
      their expression levels. The predictive accuracy of the selection is assessed by
      means of Classification and Regression Trees (CART) models which enable
      assessment of the performance of the selected genes for classifying the outcome
      variable and will also uncover complex genetic interactions. The method is
      illustrated throughout the paper using a public domain colon cancer gene
      expression data set.

PMID- 24034736
TI  - Frequent patterns mining in multiple biological sequences.
AB  - Existing algorithms for mining frequent patterns in multiple biosequences may
      generate multiple projected databases and short candidate patterns, which can
      increase computation time and memory requirement. In order to overcome such
      shortcomings, we propose a fast and efficient algorithm for mining frequent
      patterns in multiple biological sequences (MSPM). We first present the concept of
      a primary pattern, which can be extended to form larger patterns in the sequence.
      To detect frequent primary patterns, a prefix tree is constructed. Based on this
      prefix tree, a pattern-extending approach is also presented to mine frequent
      patterns without producing a large number of irrelevant candidate patterns. The
      experimental results show that the MSPM algorithm can achieve not only faster
      speed, but also higher quality results as compared with other methods.

PMID- 24034737
TI  - Morphological modeling of cardiac signals based on signal decomposition.
AB  - In this paper a general framework is presented for morphological modeling of
      cardiac signals from a signal decomposition perspective. General properties of a
      desired morphological model are presented and special cases of the model are
      studied in detail. The presented approach is studied for modeling the morphology
      of electrocardiogram (ECG) signals. Specifically, three types of ECG modeling
      techniques, including polynomial spline models, sinusoidal model and a model
      previously presented by McSharry et al., are studied within this framework. The
      proposed method is applied to datasets from the PhysioNet ECG database for
      compression and modeling of normal and abnormal ECG signals. Quantitative and
      qualitative results of these applications are also presented and discussed.

PMID- 24034738
TI  - Object information based interactive segmentation for fatty tissue extraction.
AB  - Lymph nodes are very important factors for diagnosing gastric cancer in clinical
      use, and are usually distributed within the fatty tissue around the stomach. When
      extracting fatty tissues whose structures and textures are complicated, automatic
      extraction is still a challenging task, while manual extraction is time
      consuming. Consequently, semi-automatic extraction, which allows introducing
      interactive operations, appears to be more realistic. Currently, most interactive
      methods need to indicate the position and main features in both the object and
      background. However, it is easier for radiologists to only mark object
      information. Due to this issue, a new Object Information based Interactive
      Segmentation (OIIS) method is proposed in this paper. Different from the most
      existing methods, OIIS just needs to input the object information, while the
      background information is not required. Experimental results and comparative
      studies show that OIIS is effective for fatty tissue extraction.

PMID- 24034739
TI  - Prioritization of brain MRI volumes using medical image perception model and
      tumor region segmentation.
AB  - The objective of the present study is to explore prioritization methods in
      diagnostic imaging modalities to automatically determine the contents of medical
      images. In this paper, we propose an efficient prioritization of brain MRI.
      First, the visual perception of the radiologists is adapted to identify salient
      regions. Then this saliency information is used as an automatic label for
      accurate segmentation of brain lesion to determine the scientific value of that
      image. The qualitative and quantitative results prove that the rankings generated
      by the proposed method are closer to the rankings created by radiologists.

PMID- 24034740
TI  - Intensity based image registration by minimizing exponential function weighted
      residual complexity.
AB  - In this paper, we propose a novel intensity-based similarity measure for medical
      image registration. Traditional intensity-based methods are sensitive to
      intensity distortions, contrast agent and noise. Although residual complexity can
      solve this problem in certain situations, relative modification of the parameter
      can generate dramatically different results. By introducing a specifically
      designed exponential weighting function to the residual term in residual
      complexity, the proposed similarity measure performed well due to automatically
      weighting the residual image between the reference image and the warped floating
      image. We utilized local variance of the reference image to model the exponential
      weighting function. The proposed technique was applied to brain magnetic
      resonance images, dynamic contrast enhanced magnetic resonance images (DCE-MRI)
      of breasts and contrast enhanced 3D CT liver images. The experimental results
      clearly indicated that the proposed approach has achieved more accurate and
      robust performance than mutual information, residual complexity and Jensen
      Tsallis.

PMID- 24034741
TI  - The effects of listening to music or viewing television on human gait.
AB  - This paper presents a two-part study with walking conditions involving music and
      television (TV) to investigate their effects on human gait. In the first part, we
      observed seventeen able-bodied adults as they participated in three 15-minute
      walking trials: (1) without music, (2) with music and (3) without music again. In
      the second part, we observed fifteen able-bodied adults as they walked on a
      treadmill for 15 min while watching (1) TV with sound (2) TV without sound and
      (3) TV with subtitles but no sound. Gait timing was recorded via bilateral heel
      sensors and center-of-mass accelerations were measured by tri-axial
      accelerometers. Measures of statistical persistence, dynamic stability and gait
      variability were calculated. Our results showed that none of the considered gait
      measures were statistically different when comparing music with no-music trials.
      Therefore, walking to music did not appear to affect intrinsic walking dynamics
      in the able-bodied adult population. However, stride interval variability and
      stride interval dynamics were significantly greater in the TV with sound walking
      condition when compared to the TV with subtitles condition. Treadmill walking
      while watching TV with subtitles alters intrinsic gait dynamics but potentially
      offers greater gait stability.

PMID- 24034742
TI  - MitProt-Pred: Predicting mitochondrial proteins of Plasmodium falciparum parasite
      using diverse physiochemical properties and ensemble classification.
AB  - Mitochondrial protein of Plasmodium falciparum is an important target for anti
      malarial drugs. Experimental approaches for detecting mitochondrial proteins are
      costly and time consuming. Therefore, MitProt-Pred is developed that utilizes Bi
      profile Bayes, Pseudo Average Chemical Shift, Split Amino Acid Composition, and
      Pseudo Amino Acid Composition based features of the protein sequences. Hybrid
      feature space is also developed by combining different individual feature spaces.
      These feature spaces are learned and exploited through SVM based ensemble.
      MitProt-Pred achieved significantly improved prediction performance for two
      standard datasets. We also developed the score level ensemble, which outperforms
      the feature level ensemble.

PMID- 24034743
TI  - On a reusable and multilevel methodology for modeling and simulation of
      pharmacokinetic-physiological systems: a preliminary study.
AB  - The intrinsic characteristics of physiological systems demand two critical
      requirements at the time of mathematical modeling: multilevel description and
      reusability. These features are not properly satisfied by current methodologies.
      In this paper the design of a multilevel and reusable methodology for modeling
      pharmacokinetic-physiological systems is presented. It has been implemented under
      a compliant modeling language to validate its reliability, obtaining a simulation
      components library, LibPK. A 3-pool urea kinetic model, whose vascular pool
      includes red blood cells, was built by means of LibPK. This model successfully
      confirmed the ability of this technology and the underlying methodology for
      addressing multilevel and reusability features, surpassing other physiologically
      based pharmacokinetic modeling technologies.

PMID- 24034744
TI  - Automated identification of normal and diabetes heart rate signals using
      nonlinear measures.
AB  - Diabetes mellitus (DM) affects considerable number of people in the world and the
      number of cases is increasing every year. Due to a strong link to the genetic
      basis of the disease, it is extremely difficult to cure. However, it can be
      controlled to prevent severe consequences, such as organ damage. Therefore,
      diabetes diagnosis and monitoring of its treatment is very important. In this
      paper, we have proposed a non-invasive diagnosis support system for DM. The
      system determines whether or not diabetes is present by determining the cardiac
      health of a patient using heart rate variability (HRV) analysis. This analysis
      was based on nine nonlinear features namely: Approximate Entropy (ApEn), largest
      Lyapunov exponet (LLE), detrended fluctuation analysis (DFA) and recurrence
      quantification analysis (RQA). Clinically significant measures were used as input
      to classification algorithms, namely AdaBoost, decision tree (DT), fuzzy Sugeno
      classifier (FSC), k-nearest neighbor algorithm (k-NN), probabilistic neural
      network (PNN) and support vector machine (SVM). Ten-fold stratified cross
      validation was used to select the best classifier. AdaBoost, with least squares
      (LS) as weak learner, performed better than the other classifiers, yielding an
      average accuracy of 90%, sensitivity of 92.5% and specificity of 88.7%.

PMID- 24034745
TI  - Unsupervised tumour segmentation in PET using local and global intensity-fitting
      active surface and alpha matting.
AB  - This paper proposes an unsupervised tumour segmentation approach for PET data.
      The method computes the volumes of interest (VOIs) with sub-voxel precision by
      considering the limited image resolution and partial volume effects. First, an
      improved anisotropic diffusion filter is used to remove image noise. A
      hierarchical local and global intensity active surface modelling scheme is then
      applied to segment VOIs, followed by an alpha matting step to further refine the
      segmentation boundary. The proposed method is validated on real PET images of
      head-and-neck cancer patients with ground truth provided by human experts, as
      well as custom-designed phantom PET images with objective ground truth.
      Experimental results show that our method outperforms previous automatic
      approaches in terms of segmentation accuracy.

PMID- 24034746
TI  - Cholesteryl ester transfer protein inhibitors in coronary heart disease:
      Validated comparative QSAR modeling of N, N-disubstituted trifluoro-3-amino-2
      propanols.
AB  - Cholesteryl ester transfer protein (CETP) converts high density lipoprotein
      cholesterol to low density lipoproteins. It is a promising target for treatment
      of coronary heart disease. Two dimensional quantitative structure activity
      relationship (2D-QSAR), hologram QSAR (HQSAR) studies and comparative molecular
      field analysis (CoMFA) as well as comparative molecular similarity analysis
      (CoMSIA) were performed on 104 CETP inhibitors. The statistical qualities of
      generated models were justified by internal and external validation, i.e., q(2)
      and R(2)pred respectively. The best 2D-QSAR model was obtained with q(2) and
      R(2)pred values of 0.794 and 0.796 respectively. The 2D-QSAR study suggests that
      unsaturation, branching and van der Waals volumes may play important roles. The
      HQSAR model showed q(2) and R(2)pred values of 0.628 and 0.550 respectively.
      Similarly, CoMFA model showed q(2) and R(2)pred values of 0.707 and 0.755
      respectively whereas CoMSIA model was obtained with q(2) and R(2)pred values of
      0.696 and 0.703 respectively. CoMFA and CoMSIA studies indicate that steric
      factors are important at substituted phenoxy and tetrafluoroethoxy groups whereas
      electropositive factors play important role at difluoromethyl group. The results
      of 3D-QSAR studies validate those of 2D-QSAR and HQSAR studies as well as the
      earlier observed SAR data. Current work may help to develop better CETP
      inhibitors.

PMID- 24034747
TI  - Real-time CHF detection from ECG signals using a novel discretization method.
AB  - This study proposes a new method, equal frequency in amplitude and equal width in
      time (EFiA-EWiT) discretization, to discriminate between congestive heart failure
      (CHF) and normal sinus rhythm (NSR) patterns in ECG signals. The ECG unit pattern
      concept was introduced to represent the standard RR interval, and our method
      extracted certain features from the unit patterns to classify by a primitive
      classifier. The proposed method was tested on two classification experiments by
      using ECG records in Physiobank databases and the results were compared to those
      from several previous studies. In the first experiment, an off-line
      classification was performed with unit patterns selected from long ECG segments.
      The method was also used to detect CHF by real-time ECG waveform analysis. In
      addition to demonstrating the success of the proposed method, the results showed
      that some unit patterns in a long ECG segment from a heart patient were more
      suggestive of disease than the others. These results indicate that the proposed
      approach merits additional research.

PMID- 24034748
TI  - Computer-aided diagnosis of breast cancer based on fine needle biopsy microscopic
      images.
AB  - Prompt and widely available diagnostics of breast cancer is crucial for the
      prognosis of patients. One of the diagnostic methods is the analysis of
      cytological material from the breast. This examination requires extensive
      knowledge and experience of the cytologist. Computer-aided diagnosis can speed up
      the diagnostic process and allow for large-scale screening. One of the largest
      challenges in the automatic analysis of cytological images is the segmentation of
      nuclei. In this study, four different clustering algorithms are tested and
      compared in the task of fast nuclei segmentation. K-means, fuzzy C-means,
      competitive learning neural networks and Gaussian mixture models were
      incorporated for clustering in the color space along with adaptive thresholding
      in grayscale. These methods were applied in a medical decision support system for
      breast cancer diagnosis, where the cases were classified as either benign or
      malignant. In the segmented nuclei, 42 morphological, topological and texture
      features were extracted. Then, these features were used in a classification
      procedure with three different classifiers. The system was tested for
      classification accuracy by means of microscopic images of fine needle breast
      biopsies. In cooperation with the Regional Hospital in Zielona Gora, 500 real
      case medical images from 50 patients were collected. The acquired classification
      accuracy was approximately 96-100%, which is very promising and shows that the
      presented method ensures accurate and objective data acquisition that could be
      used to facilitate breast cancer diagnosis.

PMID- 24034749
TI  - Computational method for high resolution spectral analysis of fractionated atrial
      electrograms.
AB  - BACKGROUND: The discrete Fourier transform (DFT) is often used as a spectral
      estimator for analysis of complex fractionated atrial electrograms (CFAE)
      acquired during atrial fibrillation (AF). However, time resolution can be
      unsatisfactory, as the frequency resolution is proportional to rate/time
      interval. In this study we compared the DFT to a new spectral estimator with
      improved time-frequency resolution. METHOD: Recently, a novel spectral estimator
      (NSE) based upon signal averaging was derived and implemented computationally.
      The NSE is similar to the DFT in that both estimators model the autocorrelation
      function to form the power spectrum. However, as derived in this study, NSE
      frequency resolution is proportional to rate/period(2) and thus unlike the DFT,
      is not directly dependent on the window length. We hypothesized that the NSE
      would provide improved time resolution while maintaining satisfactory frequency
      resolution for computation of CFAE spectral parameters. Window lengths of 8s, 4s,
      2s, 1s, and 0.5s were used for analysis. Two criteria gauged estimator
      performance. Firstly, a periodic electrogram pattern with phase jitter was
      embedded in interference. The error in detecting the frequency of the periodic
      pattern was determined. Secondly, significant differences in spectral parameters
      for paroxysmal versus persistent AF data, which have known dissimilarities, were
      determined using the DFT versus NSE methods. The parameters measured were the
      dominant amplitude, dominant frequency, and mean spectral profile. RESULTS: At
      all time resolutions, the error in detecting the frequency of the repeating
      electrogram pattern was less for NSE than for DFT (p<0.001). The DFT was accurate
      to 2s time resolution/0.5 Hz frequency resolution, while the NSE was accurate to
      0.5s time resolution/0.05 Hz frequency resolution. At all time resolutions,
      significant differences in the dominant amplitude spectral parameter for
      paroxysmal versus persistent CFAE were greater using NSE than DFT (p<0.0001). For
      three of five time resolutions, the NSE had greater significant differences than
      DFT for discriminating the dominant frequency and mean spectral profile
      parameters between AF types. CONCLUSIONS: The results suggest that the NSE has
      improved performance versus DFT for measurement of CFAE spectral properties.

PMID- 24034750
TI  - Evaluation of a novel automated non-invasive pulse pressure variation algorithm.
AB  - In mechanically ventilated patients, Pulse Pressure Variation (PPV) has been
      shown to be a useful parameter to guide fluid management. We evaluated a real
      time automated PPV-algorithm by comparing it to manually calculated PPV-values.
      In 10 critically ill patients, blood pressure was measured invasively (IBP) and
      non-invasively (CNAP((r)) Monitor, CNSystems Medizintechnik, Austria). PPV was
      determined manually and compared to automated PPV values: PPVmanIBP vs.
      PPVautoIBP was -0.19 +/- 1.65% (mean bias +/- standard deviation), PPVmanCNAP vs.
      PPVautoCNAP was -1.02 +/- 2.03% and PPVautoCNAP vs. PPVmanIBP was -2.10 +/-
      3.14%, suggesting that the automated CNAP((r)) PPV-algorithm works well on both
      blood pressure waveforms but needs further clinical evaluation.

PMID- 24034751
TI  - Modeling hybrid rough set-based classification procedures to identify
      hemodialysis adequacy for end-stage renal disease patients.
AB  - Healthcare problems observed in the majority of end-stage renal disease (ESRD)
      patients regarding hemodialysis (HD) treatment are serious issues for the
      Taiwanese healthcare services, and an interesting topic is thus the adequacy of
      HD therapy. This study successfully models a hybrid procedure to measure HD
      adequacy to assess therapeutic effects and to explore the relationship between
      accuracy and coverage for interested parties. The proposed model has better
      accuracy, a lower standard deviation, and fewer attributes than the listed
      methods under various evaluation criteria. The study results are useful to
      subsequent researchers to develop suitable applications, and to ESRD patients and
      their doctors to ensure satisfactory medical quality.

PMID- 24034752
TI  - A new approach to modeling of selected human respiratory system diseases,
      directed to computer simulations.
AB  - This paper presents a new versatile approach to model severe human respiratory
      diseases via computer simulation. The proposed approach enables one to predict
      the time histories of various diseases via information accessible in medical
      publications. This knowledge is useful to bioengineers involved in the design and
      construction of medical devices that are employed for monitoring of respiratory
      condition. The approach provides the data that are crucial for testing diagnostic
      systems. This can be achieved without the necessity of probing the physiological
      details of the respiratory system as well as without identification of parameters
      that are based on measurement data.

PMID- 24034753
TI  - A context evaluation approach for structural comparison of proteins using cross
      entropy over n-gram modelling.
AB  - The structural comparison of proteins is a vital step in structural biology that
      is used to predict and analyse a new unknown protein function. Although a number
      of different techniques have been explored, the study to develop new alternative
      methods is still an active research area. The present paper introduces a text
      modelling-based technique for the structural comparison of proteins. The method
      models the secondary and tertiary structure of proteins in two linear sequences
      and then applies them to the comparison of two structures. The technique used for
      pairwise comparison of the sequences has been adopted from computational
      linguistics and its well-known techniques for analysing and quantifying textual
      sequences. To this end, an n-gram modelling technique is used to capture
      regularities between sequences, and then, the cross-entropy concept is employed
      to measure their similarities. Several experiments are conducted to evaluate the
      performance of the method and compare it with other commonly used programs. The
      assessments for information retrieval evaluation demonstrate that the technique
      has a high running speed, which is similar to other linear encoding methods, such
      as 3D-BLAST, SARST, and TS-AMIR, whereas its accuracy is comparable to CE and TM
      align, which are high accuracy comparison tools. Accordingly, the results
      demonstrate that the algorithm has high efficiency compared with other state-of
      the-art methods.

PMID- 24034754
TI  - Research of fetal ECG extraction using wavelet analysis and adaptive filtering.
AB  - Extracting clean fetal electrocardiogram (ECG) signals is very important in fetal
      monitoring. In this paper, we proposed a new method for fetal ECG extraction
      based on wavelet analysis, the least mean square (LMS) adaptive filtering
      algorithm, and the spatially selective noise filtration (SSNF) algorithm. First,
      abdominal signals and thoracic signals were processed by stationary wavelet
      transform (SWT), and the wavelet coefficients at each scale were obtained. For
      each scale, the detail coefficients were processed by the LMS algorithm. The
      coefficient of the abdominal signal was taken as the original input of the LMS
      adaptive filtering system, and the coefficient of the thoracic signal as the
      reference input. Then, correlations of the processed wavelet coefficients were
      computed. The threshold was set and noise components were removed with the SSNF
      algorithm. Finally, the processed wavelet coefficients were reconstructed by
      inverse SWT to obtain fetal ECG. Twenty cases of simulated data and 12 cases of
      clinical data were used. Experimental results showed that the proposed method
      outperforms the LMS algorithm: (1) it shows improvement in case of superposition
      R-peaks of fetal ECG and maternal ECG; (2) noise disturbance is eliminated by
      incorporating the SSNF algorithm and the extracted waveform is more stable; and
      (3) the performance is proven quantitatively by SNR calculation. The results
      indicated that the proposed algorithm can be used for extracting fetal ECG from
      abdominal signals.

PMID- 24034755
TI  - Atrial activity selection for atrial fibrillation ECG recordings.
AB  - In this paper we apply independent component analysis (ICA) followed by second
      order blind identification (SOBI) to an atrial fibrillation (AF) 12-lead
      electrocardiogram (ECG) recording in order to extract the source that represents
      atrial activity (AA) (ICA-SOBI method). Still, there is no assurance that only
      one source obtained from this method will contain AA, and thus we aim to select
      the most representative source of AA. The novelty in this paper is the proposal
      of three parameters to select the most representative source of AA. These
      parameters are correlation coefficient with lead V1 (CV1), peak factor (PF) and
      spectral concentration (SC). The first two parameters are introduced as new
      indicators, addressing features overlooked by the SC even when they are present
      in AA during AF. For synthesized data, at least two of the three parameters
      select the same representation of AA in 93.3% of the cases. For real data (218
      ECG recordings), we observe that PF presents, in 89.5% of the cases, values
      between 2 and 4.5 for the selected sources, ensuring a well-defined range of
      values for AA. The actual values of CV1 and SC were scattered throughout their
      possible ranges (0-1 for CV1 and 0.08-0.7 for SC), and the correlation
      coefficient between these variables was found to be rho=0.58. We compared our
      results with three known algorithms: QRST cancellation, principal components
      analysis (PCA) and ICA-SOBI. The results obtained from this comparison show that
      our proposed methods to select the best representation of AA in general
      outperform the three above-mentioned algorithms.

PMID- 24034756
TI  - [Evaluation of the capacity of elderly patients to make decisions about their
      health].
AB  - OBJECTIVE: To assess the decision-making capacity and variables related to this,
      in elderly patients in a home care program. MATERIAL AND METHODS: A cross
      sectional study was conducted on 130 patients assigned to home care program or in
      social welfare residences of an urban health centre. Demographic variables, as
      well as comorbidities, social support, institutionalisation, number of drugs
      used, degree of dependence (Barthel Index), cognitive function (Pfeiffer) were
      collected. The primary endpoint was the capacity for decision-making about their
      health assessed using the Aid to Capacity Evaluation (ACE) tool. RESULTS: There
      was a prevalence of 58.5% capacity. There was an association between ability and
      independence for activities of daily living (odds ratio (OR): 12.214; Confidence
      interval 95% (95% CI): 3.90 to 32.29, P <.0001) and function intellectual intact
      (OR: 282.750, 95% CI 34.0 to 2351.2, P <.0001). Numeric variables associated with
      the capacity for decision-making that had a more important effect size were the
      Barthel index (d: -1.398) and Pfeiffer index (d: 3.084). CONCLUSIONS: The
      prevalence of incapacity to make decisions about their health in elderly patients
      who are cared for in their homes is high. The level of dependence in activities
      of daily living and the deterioration of intellectual function are factors
      associated with the presence of this capacity.

PMID- 24034757
TI  - [Lipid profile in patients admitted with acute coronary syndrome in Spain: data
      from Toledo health care area between 2005 and 2008].
AB  - INTRODUCTION AND OBJECTIVES: To evaluate the lipid profile of patients admitted
      with acute coronary syndrome in Toledo (Spain) between 2005 and 2008. METHODS:
      Total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride levels were
      evaluated. Descriptive analyses and means comparison were performed. RESULTS:
      1,381 patients of 3,986 admitted with acute coronary syndrome had a complete
      lipid profile. The mean age was 67.8+/-12.9 years (72.4% men). A first event was
      present in 76.3%. The mean total cholesterol (+/-SD) was 180.0+/-43.4, LDL
      cholesterol 115+/-38.0, HDL-cholesterol 44.1+/-12.3, and triglyceride 145.3+/
      92.4mg/dL, with statistically significant differences between men and women in
      LDL-cholesterol (116.3+/-37.8 vs 111.6+/-38.5mg/dL; p=0.04) and HDL-cholesterol
      (42.3+/-11.6 vs 48.4+/-13.2mg/dL; p=0.0001). In first or recurrent events were
      found, respectively, total cholesterol 179.1+/-43.1 and 174.5+/-44.1 (p<0.05),
      LDL-cholesterol 116.5+/-38.4 and 110+/-36.5 (p=0.007), HDL-cholesterol 44.1+/
      12.2 and 44.2+/-12.9 (p<0.05), and triglyceride 141.2+/-81.7 and 158.5+/-119.7
      (p=0.03). Optimal levels of LDL-cholesterol and HDL-cholesterol were found in
      14.1 and 11.6% of patients with recurrent episodes, respectively. CONCLUSIONS:
      While most patients admitted with first episode of acute coronary syndrome to the
      Toledo Health Area have a lipid profile according to current guidelines, only 10%
      of those with recurrent acute coronary syndrome presented optimal LDL-cholesterol
      and HDL-cholesterol levels, which suggest the need to be more aggressive in the
      lipids control.

PMID- 24034758
TI  - [Use of topical non-steroidal anti-inflammatory agents in an urban health center.
      Comparison with the current evidence].
AB  - OBJECTIVE: To describe the prescribing of topical non-steroidal anti-inflammatory
      drugs (NSAIDs) in an urban health center (Zaragoza, Spain). PATIENTS AND METHODS:
      A cross-sectional descriptive study was conducted on subjects who belonged to an
      urban center and were studied during the year 2010. The sample size with a
      confidence level of 95%, was calculated, a total of 843 prescriptions were
      analyzed. The sample was single random, and 150 cases were selected. The
      prevalence and confidence intervals were calculated. The statistical package
      STATA 9.1 was used for the calculations. RESULTS: The most used drug was
      diclofenac, in 27.33% (95% CI: 20.65-34.88). NSAIDs were most used in females. In
      18% of the cases the area of application was the knee, followed by the 15% in the
      lower back area (95% CI: 10,22-21,78). There were no adverse reactions.
      CONCLUSIONS: Frequent use is made of topical NSAIDs in a basic health area.
      Current recommendations support the use in the knee and in the hand, but not in
      the back, where its use is common. The use of topical NSAIDs decreases side
      effects and drug interactions, therefore their use is recommended in patients on
      multiple drug therapy and in the elderly.

PMID- 24034759
TI  - [The enigma of quaternary prevention in Primary Care. When and when not to do it
      (presentation of two cases)].
AB  - Quaternary prevention has been commonly defined with the "primum non nocere" of
      classical texts by many authors. The daily life of our primary care consultations
      are full of patients in which we wondered if we try to obtain the benefit of our
      intervention will exceed the damage we cause him to intervene. Patients with
      multiple comorbidities, polypharmacy and complex are common in our consultations
      and it is becoming more difficult to move the balance of our actions, diagnostic
      or therapeutic benefit to the side. Through 2 cases often move to the reflection
      of this problem. Quaternary prevention must also be present in our daily
      activities.

PMID- 24034760
TI  - [Chronic migraine and work: occupational risks and prevention].
AB  - Chronic migraine is a clinically difficult to manage primary headache which
      affects the quality of life of the patients. This impact is important in the
      occupational world, where along with the clinical aspects of the disease, the
      therapies used for the control of the symptoms or preventive aspects, must be
      assessed. The side effects of the drugs and the limitations associated with their
      symptoms are aspects to highlight in occupational health, especially in
      individual workplaces, where there is a high risk of work-related injuries. The
      medical officer must assess the occupational risks of particular importance in
      the progression of this disease, as well as preventive actions, within the ambit
      of the current Spanish legislation, that may be favorable for both the company
      and the worker. The coordinated medical intervention and knowledge of these
      occupational aspects can provide clinically relevant tools, andoccupational and
      social optimization in the use of available resources.

PMID- 24034761
TI  - [Polyarthralgia as an initial symptom of sarcoidosis].
AB  - A 39 year-old patient consulted his family doctor due to migratory
      polyarthralgia, with C-reactive protein 7.99mg/dl, ESR 89mm and normal anti
      streptolysin O (ASO). A sample was taken for analysis in the Rheumatology Clinic:
      ACE 72 IU, with normal rheumatoid factor, C-reactive protein and ASO; HLA non
      specific. Chest X-ray showed an increased pulmonary interstitial pattern, and his
      chest-CT showed multiple bilateral pulmonary nodules and mediastinal lymph nodes.
      A differential diagnosis of lymphoproliferative process was considered. A gallium
      scintigraphy was performed with no relevant findings. The patient was referred to
      Thoracic Surgery for a lymph node biopsy by mediastinoscopy, which showed a non
      necrotizing granulomatous lymphadenitis consistent with a sarcoidosis. Treatment
      with prednisone and anti-osteoporosis drugs was started and the patient was
      evaluated at four months with a new chest X-ray. There was a clinical and
      radiological remission therefore it was decided to gradually reduce the
      corticosteroid therapy.

PMID- 24034762
TI  - [Methylphenidate and secondary Raynaud's phenomenon].
AB  - Raynaud's phenomenon is a clinical disease characterized by episodic attacks of
      vasoconstriction of the arteries and arterioles of the extremities such as
      fingers and toes, sometimes the ears and nose, in response to cold or emotional
      stimuli. A classic attack is the pallor of the distal extremity, followed by
      cyanosis and redness, accompanied by paresthesia, usually as heat. When it occurs
      without apparent cause is called primary Raynaud's phenomenon. When associated
      with other disease, is called secondary Raynaud's phenomenon. The secondary table
      is associated with increased frequency of rheumatic diseases of collagen. They
      can also present certain drugs that cause vasoconstriction, such as ergotamine,
      beta-adrenergic antagonists, contraception and sympathomimetic drugs. Regarding
      the latter, we present a case of Raynaud's phenomenon secondary to
      methylphenidate in a 14 years.

PMID- 24034763
TI  - [Diagnosis of multiple myeloma in primary care. Suspicion with an appropriate
      clinical history].
AB  - Monoclonal gammopathies are a group of disorders characterized by stable or
      progressive clonal proliferation of plasma cells producing similar
      immunoglobulins. Multiple myeloma is characteristic of the presence of bone
      marrow infiltration by plasma cells, osteolytic lesions, and M component in serum
      or urine. As cancer cells multiply, they can cause pain and destruction of bone,
      and if affecting the spine, they can press on nerves causing pain and
      paresthesias. In patients of advanced age (average 69 years) with bone pain not
      associated with trauma, and which does not improve with treatment, a differential
      diagnosis should be performed with multiple myeloma. This should include, at
      least, a full blood count, biochemistry, total protein, protein electrophoresis,
      immunofixation, and radiographs of painful areas.

PMID- 24034764
TI  - [Primary presentation of non-hodgkin lymphoma. Report of a case].
AB  - Lymphomas are the most common non-epithelial tumors of the head and neck and its
      incidence has increased in recent decades. Around 10% are extranodal lymphomas,
      and in more than half of the cases are located in Waldeyer's lymphatic ring. The
      most common presenting symptoms are odynophagia and dysphagia (68%), and symptoms
      suggestive of oropharyngeal cancer such as cough, hoarseness, earache, feeling of
      occupation in the back of the mouth, throat or neck. In non-Hodgkin lymphomas in
      this location, B symptoms (weight loss, fever and sweating) are rare (5%). The
      histological subtype of each individual lymphoma affects the evaluation, therapy
      and prognosis.

PMID- 24034765
TI  - [Chronic tophaceous gout].
AB  - Gout is a common illness, usually of unknown etiology, is more frequent in men,
      and with a prevalence that increases with age. It is characterized by recurrent
      episodes of acute arthritis due to the deposition of monosodium urate crystals in
      joints. The underlying disorder in most cases is hyperuricemia, usually as a
      consequence of impairment in its renal excretion. Although it is generally
      believed that both the diagnosis and treatment are simple, the truth is that the
      level of adherence of clinical decisions using the existing guidelines is poor.
      We describe a case of chronic tophaceous gout, and review the general
      characteristics of this condition. 

PMID- 24034766
TI  - [Odynophagia, fever and rash in a 33 year-old woman].
AB  - Hand-Foot-Mouth disease is a viral exanthematous disease primarily caused by
      Coxsackie virus that mainly affects children under 10 years-old during the spring
      or summer. It is a rare disease in adults, and rarer still in the
      immunocompetent. We report the case of a 33-year-old immunocompetent adult
      affected bys Hand Foot Mouth disease.

PMID- 24034767
TI  - [Management of onychocryptosis in primary care: A clinical case].
AB  - Onychocryptosis (ingrown toenail) is a condition commonly seen in Primary Care
      clinics. It is uncomfortable and restrictive for patients and has a high
      incidence in males between second and third decades of life. It is of unknown
      origin, with a number of predisposing triggering factors being involved.
      Treatment depends on the stage of the ingrown nail and the procedures may range
      from conservative to minor surgery that can be performed by the Primary Care
      physician in the health centre. We report the case of a 25-year onychocryptosis
      that did not respond to conservative management, and was extracted with partial
      matricectomy of the nail.

PMID- 24034768
TI  - In this issue of Healthcare Quarterly.

PMID- 24034769
TI  - Seniors and alternative level of care: building on our knowledge.
AB  - There is ongoing concern that acute care beds in Canada are occupied by seniors
      who are waiting to be discharged to a more appropriate level of care. These
      individuals, who no longer require acute care services, are commonly designated
      as alternative level of care (ALC) patients. In this study, the authors examined
      the characteristics of patients transitioning from acute care to home care or
      residential care. 

PMID- 24034770
TI  - Youth suicide in Canada: distinctions among boys and girls.
AB  - In Canada, boys account for almost three quarters of suicides among those aged 15
      24 years. However, non-fatal suicide-related behaviours also onset in youth but
      are more common in girls. Thus far, there has been little empirical investigation
      of what produces this gender paradox. This report summarizes two recently
      published studies in which ICES tackles the issues of the potential impacts of
      misclassification of suicide and of help-seeking behaviour. 

PMID- 24034771
TI  - Canada's top 5 in 5.
AB  - In 2011, the Canadian Nurses Association made a decision to establish and fund a
      national commission focused on health system transformation, the National Expert
      Commission. In 2012, the commission presented an action plan, the lead
      recommendation of which was to ensure that Canada ranks among the top five
      nations on five key population health status and system performance indicators in
      the next five years. In this article, the authors outline the selection of the
      these indicators and the associated goals for improvement. 

PMID- 24034772
TI  - In conversation with Sholom Glouberman.

PMID- 24034773
TI  - Creating the right evidence for system change.
AB  - Most evaluative research is focused on assessing new technologies at the patient
      level. Comparatively little is focused on assessing how system changes could
      improve the delivery of healthcare. In this article, the authors describe an
      opportunity to conduct evaluative trials of system changes affordably and
      efficiently by using a cluster randomized design and mandatory reporting data,
      using the prevention of Clostridium difficile infection as an example. They then
      describe what must be done to make similar trials a regular tool of healthcare
      policy. 

PMID- 24034774
TI  - The value of collecting population-based cancer stage data to support decision
      making at organizational, regional and population levels.
AB  - The stage of a patient's cancer at diagnosis is essential to predict the
      prognosis and plan the treatment. Since 2008, stage data have been collected on
      all Ontario patients with breast, colorectal, lung and prostate cancers and are
      linked to other data collected by Cancer Care Ontario. Here, an analysis of such
      data is presented. How it can be used to assess the value of screening programs,
      inform resource allocation, evaluate compliance with treatment guidelines,
      compare survival trends and enhance the spectrum of cancer control activities
      across the province is demonstrated. International comparisons can also be made. 

PMID- 24034775
TI  - Assessing the feasibility of extracting clinical information to create quality
      indicators from primary healthcare practice EMRs.
AB  - In 2011, a panel of primary healthcare (PHC) providers in Nova Scotia rated 19 of
      35 selected Canadian Institute for Health Information (2006) clinical quality
      indicators (QIs) as "acceptable." In this study, the authors explored the
      feasibility of extracting electronic medical record (EMR) data required to create
      these PHC QI measures. 

PMID- 24034776
TI  - Piloting an outpatient policy for funding drugs and their administration in
      rheumatology.
AB  - To ensure appropriate use of outpatient clinic resources, an inter-professional
      group drafted a policy for an equitable, consistent process requiring the use of
      patients' drug insurance. The authors' organization remains the payer of last
      resort. A pilot tested and further informed this policy by targeting rituximab in
      rheumatoid arthritis. Staff were in-serviced, resources were arranged and
      patients were informed. Thirty-nine pilot patients (87%) had drug insurance,
      resulting in a savings of $304,700. Fifty-one hospital infusions were
      administered in private clinics, avoiding $19,125 in clinic costs. Patient and
      staff/stakeholder satisfaction surveys provided valuable feedback. Lessons
      learned will be applied to the policy and related processes in preparation for an
      organizational-wide implementation. 

PMID- 24034777
TI  - Legal implications of single-use medical device reprocessing.
AB  - Over 10 years ago, the Public Health Agency of Canada released the results of a
      nation-wide survey of hospitals that demonstrated that the reuse of single-use
      medical devices was widespread in Canadian healthcare institutions. In this
      article, the author discusses the reuse and reprocessing of these devices, as
      well as the risks this practice presents. She then goes on to outline the legal
      implications of reusing single-use devices. 

PMID- 24034778
TI  - Inter-professional clinical placements as a recruitment strategy in geriatrics:
      survey of students' perceptions.
AB  - Inter-professional (IP) education and clinical placements have been identified as
      educational recruitment strategies to address the health workforce shortage. The
      research question in this secondary analysis study was, "What are students'
      attitudes toward working in geriatric environments and as part of inter
      professional collaborative teams?" A five-item survey was administered to 47 pre
      licensure learners from five different health professional programs (medicine,
      nursing, pharmacy, occupational therapy and physical therapy). Findings suggest
      that students want to practise on IP teams, which may influence their graduate
      first choice of employment. Although stronger evidence is required, offering IP
      clinical placements may be an important recruitment strategy, especially for
      those sites traditionally deemed less desirable. 

PMID- 24034781
TI  - Neurosurgical interventions for patients with nasopharyngeal carcinoma: a single
      institution experience.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a frequent head and neck cancer in
      southern China and Southeast Asia. The majority of NPC patients are managed by
      radiation oncologists, medical oncologists and head and neck surgeons. Actually,
      neurosurgical interventions are warranted under specific circumstances. In this
      article, we described our experience as neurosurgeons in the management of NPC
      patients. METHODS: Medical records of NPC patients who received neurosurgical
      procedure at Sun Yat-sen University Cancer Center were reviewed. RESULTS: Twenty
      seven patients were identified. Among 27 cases, neurosurgical procedures were
      performed in 18 (66.7%) with radiation-induced temporal necrosis, 2 (7.4%) with
      radiation-induced sarcoma, 4 (14.8%) with synchronous NPC with primary brain
      tumors, 2 (7.4%) with recurrent NPC involving skull base, and 1 (3.7%) with
      metachronous skull eosinophilic granuloma, respectively. The diagnosis is
      challenging in specific cases and initial misdiagnoses were found in 6 (22.2%)
      patients. CONCLUSIONS: For NPC patients with intracranial or skull lesions, the
      initial diagnosis can be occasionally difficult because of the presence or a
      history of NPC and related treatment. Unawareness of these entities can result in
      misdiagnosis and subsequent improper treatment. Neurosurgical interventions are
      necessary for the diagnosis and treatment for these patients.

PMID- 24034780
TI  - LINEs of evidence: noncanonical DNA replication as an epigenetic determinant.
AB  - LINE-1 (L1) retrotransposons are repetitive elements in mammalian genomes. They
      are capable of synthesizing DNA on their own RNA templates by harnessing reverse
      transcriptase (RT) that they encode. Abundantly expressed full-length L1s and
      their RT are found to globally influence gene expression profiles,
      differentiation state, and proliferation capacity of early embryos and many types
      of cancer, albeit by yet unknown mechanisms. They are essential for the
      progression of early development and the establishment of a cancer-related
      undifferentiated state. This raises important questions regarding the functional
      significance of L1 RT in these cell systems. Massive nuclear L1-linked reverse
      transcription has been shown to occur in mouse zygotes and two-cell embryos, and
      this phenomenon is purported to be DNA replication independent. This review
      argues against this claim with the goal of understanding the nature of this
      phenomenon and the role of L1 RT in early embryos and cancers. Available L1 data
      are revisited and integrated with relevant findings accumulated in the fields of
      replication timing, chromatin organization, and epigenetics, bringing together
      evidence that strongly supports two new concepts. First, noncanonical replication
      of a portion of genomic full-length L1s by means of L1 RNP-driven reverse
      transcription is proposed to co-exist with DNA polymerase-dependent replication
      of the rest of the genome during the same round of DNA replication in embryonic
      and cancer cell systems. Second, the role of this mechanism is thought to be
      epigenetic; it might promote transcriptional competence of neighboring genes
      linked to undifferentiated states through the prevention of tethering of involved
      L1s to the nuclear periphery. From the standpoint of these concepts, several
      hitherto inexplicable phenomena can be explained. Testing methods for the model
      are proposed.

PMID- 24034782
TI  - Evidence of transmission and risk factors for influenza A virus in household dogs
      and their owners.
AB  - BACKGROUND: The possible transmission of influenza A virus between dogs and
      humans is important, as in Mexico City there are approximately 1.2 million dogs.
      We present the first evidence of influenza A virus infection in household dogs in
      Mexico. OBJECTIVES: The objective of this study was to identify the presence of
      antibodies against influenza A virus in dogs and their owners, as well as the
      presence of RNA of influenza A virus in nasal exudates of dogs and, thereby,
      assess the possible transmission of the virus between humans and dogs. METHODS:
      Serum samples from household dogs and their owners were analyzed to detect the
      presence of antibodies against three subtypes of human influenza virus
      (H1N1pdm09, H1N1, and H3N2), as well as subtype H3N8 of equine influenza. We
      analyzed dog nasal exudates to detect influenza viral RNA. The relationship
      between the seropositivity of dogs and various factors (age, sex, constantly at
      home, and seropositivity of owners) was statistically analyzed. RESULTS:
      Seroprevalence for human influenza in dogs was 0.9% (1 of 113), and it was 4% (5
      of 113) for equine influenza. In humans, seroprevalence was 22% for subtype
      H1N1pdm09, 20% for subtype H1N1, and 11% for subtype H3N2. No significant
      association (P>0.05) was found between seropositivity and any of the assessed
      factors. Furthermore, no viral RNA was detected in the nasal exudate samples.
      CONCLUSIONS: Results revealed seroprevalence of the influenza virus in household
      dogs in Mexico City. It can be assumed that dogs are currently becoming infected
      with different subtypes of influenza viruses.

PMID- 24034783
TI  - Lead, mercury, and cadmium exposure and attention deficit hyperactivity disorder
      in children.
AB  - BACKGROUND: There is limited research examining the relationship between lead
      (Pb) exposure and medically diagnosed attention deficit hyperactivity disorder
      (ADHD) in children. The role of mercury (Hg) and cadmium (Cd) exposures in ADHD
      development is even less clear. OBJECTIVES: To examine the relationship between
      Pb, Hg, and Cd and ADHD in children living inside and outside a Lead
      Investigation Area (LIA) of a former lead refinery in Omaha, NE. METHODS: We
      carried out a case-control study with 71 currently medically diagnosed ADHD cases
      and 58 controls from a psychiatric clinic and a pediatric clinic inside and
      outside of the LIA. The participants were matched on age group (5-8, 9-12 years),
      sex, race (African American or Caucasians and others), and location (inside or
      outside LIA). We measured whole blood Pb, total Hg, and Cd using inductively
      coupled plasma mass spectrometry. RESULTS: Inside the LIA, the 27 cases had blood
      Pb geometric mean (GM) 1.89 ug/dL and the 41 controls had 1.51 ug/dL. Outside the
      LIA, the 44 cases had blood Pb GM 1.02 ug/dL while the 17 controls had 0.97
      ug/dL. After adjustment for matching variables and maternal smoking,
      socioeconomic status, and environmental tobacco exposure, each natural log unit
      blood Pb had an odds ratio of 2.52 with 95% confidence interval of 1.07-5.92.
      Stratification by the LIA indicated similar point estimate but wider CIs. No
      associations were observed for Hg or Cd. CONCLUSIONS: Postnatal Pb exposure may
      be associated with higher risk of clinical ADHD, but not the postnatal exposure
      to Hg or Cd.

PMID- 24034784
TI  - Determinants of personal, indoor and outdoor VOC concentrations: an analysis of
      the RIOPA data.
AB  - Community and environmental exposure to volatile organic compounds (VOCs) has
      been associated with a number of emission sources and activities, e.g.,
      environmental tobacco smoke and pumping gasoline. Such factors have been
      identified from mostly small studies with relatively limited information
      regarding influences on VOC levels. This study uses data from the Relationship of
      Indoor Outdoor and Personal Air (RIOPA) study to investigate environmental,
      individual and social determinants of VOC concentrations. RIOPA included outdoor,
      indoor and personal measurements of 18 VOCs from 310 non-smoking households and
      adults in three cities and two seasons, and collected a wide range of information
      pertaining to participants, family members, households, and neighborhoods.
      Exposure determinants were identified using stepwise regressions and linear mixed
      effect models. Most VOC exposure (66 to 78% of the total exposure, depending on
      VOC) occurred indoors, and outdoor VOC sources accounted for 5 (d-limonene) to
      81% (carbon tetrachloride) of the total exposure. Personal exposure and indoor
      measurements had similar determinants, which depended on the VOC. Gasoline
      related VOCs (e.g., benzene, methyl tertiary butyl ether) were associated with
      city, residences with attached garages, self-pumping of gas, wind speed, and
      house air exchange rate (AER). Odorant and cleaning-related VOCs (e.g., 1,4
      dichlorobenzene and chloroform) also were associated with city and AER, and with
      house size and family members showering. Dry-cleaning and industry-related VOCs
      (e.g., tetrachloroethylene and trichloroethylene) were associated with city,
      residence water supply type, and dry-cleaner visits. These and other
      relationships were significant, explained from 10 to 40% of the variation, and
      are consistent with known emission sources and the literature. Outdoor
      concentrations had only two common determinants: city and wind speed. Overall,
      personal exposure was dominated by the home setting, although a large fraction of
      VOC concentrations were due to outdoor sources. City, personal activities,
      household characteristics and meteorology were significant determinants.

PMID- 24034786
TI  - Association between radiological findings and severity of community-acquired
      pneumonia in children.
AB  - BACKGROUND: There are few published data concerning radiological findings and
      their relationship with community-acquired pneumonia (CAP) severity. The aim if
      this study was to assess radiographic findings in children with CAP of different
      severity in order to evaluate whether some parameters are associated with severe
      CAP. METHODS: We analysed the characteristics of parenchymal densities in 335
      chest radiographs of otherwise healthy children (173 males; mean age +/- standard
      deviation, 7.5 +/- 4.5 years) admitted to our Emergency Room for CAP. Upon
      admission, chest radiographs were obtained in the two standard projections, and
      the children with severe or mild/moderate CAP were compared in order to identify
      any correlations between CAP severity and the radiological findings. RESULTS:
      Seventy-six of the 335 enrolled children (22.7%) fulfilled the criteria for
      severe CAP. In comparison with the children with mild/moderate CAP, in severe CAP
      there was a significantly greater frequency of a bilateral multifocal
      distribution (p = 0.01), the simultaneous involvement of >= 3 sites (p = 0.007),
      and the involvement of the right hilum (p = 0.02). The same results were
      confirmed in the multiple logistic regression model. CONCLUSIONS: This study
      shows that radiological findings such as a multifocal bilateral distribution, the
      simultaneous involvement of at least three sites, and right hilar consolidation
      are associated with severe CAP in otherwise healthy children, and could be
      considered markers of disease severity in children with CAP.

PMID- 24034787
TI  - Single-nucleotide polymorphism C3435T in the ABCB1 gene is associated with opioid
      consumption in postoperative pain.
AB  - BACKGROUND: ABCB1 is a major determinant of opioid bioavailability; however, no
      previous studies have provided positive evidence of an association between single
      nucleotide polymorphisms (SNPs) of ABCB1 and opioid usage in acute pain
      management. The aim of this study was to test the association between the
      functional SNP C3435T in ABCB1 and opioid consumption in postoperative pain in
      patients undergoing a nephrectomy. Additionally, we explored the association
      between C3435T and opioid side effect. METHODS: C3435T was genotyped in 152
      patients undergoing a nephrectomy. Opioid consumption and pain scores were
      evaluated as well. The effect of genotype on opioid consumption was modeled using
      a general linear mixed model. RESULT: Based on a mixed linear model, the ABCB1
      three genotypes showed a statistically significant effect on opioid consumption
      (F = 4.20, P = 0.017). There was a statistically significant difference in opioid
      consumption among the ABCB1 three genotypes in the 0-6 hours (P = 0.031, 95%
      confidence interval [CI] CC 14.7-24.8 mg and TT 5.2-14.6 mg) and 6-12 hours (P =
      0.009, 95% CI CC 5.6-13.8 mg and TT 1.2 mg-5.1 mg) postoperative period. There
      were no significant statistical differences in opioid consumption among the ABCB1
      three genotypes in the 12-24 hours (P = 0.302) and 24-48 hours (P = 0.763)
      postoperative period. The TT genotype had significantly lower levels of
      cumulative opioid consumption compared with the CC genotype in first 24 hours
      after surgery (P = 0.029). No statistically significant differences among the
      three genotype groups were noted for postoperative pain scores or emesis
      medication use in the first 24 hours after surgery. CONCLUSION: Our results
      demonstrate an association between the ABCB1 polymorphism (C3435T) and
      interindividual variations in opioid consumption in the acute postoperative
      period after nephrectomy. The ABCB1 polymorphism may serve as an important factor
      to guide acute pain therapy in postoperative patients.

PMID- 24034785
TI  - A combination of improved differential and global RNA-seq reveals pervasive
      transcription initiation and events in all stages of the life-cycle of functional
      RNAs in Propionibacterium acnes, a major contributor to wide-spread human
      disease.
AB  - BACKGROUND: Sequencing of the genome of Propionibacterium acnes produced a
      catalogue of genes many of which enable this organism to colonise skin and
      survive exposure to the elements. Despite this platform, there was little
      understanding of the gene regulation that gives rise to an organism that has a
      major impact on human health and wellbeing and causes infections beyond the skin.
      To address this situation, we have undertaken a genome-wide study of gene
      regulation using a combination of improved differential and global RNA-sequencing
      and an analytical approach that takes into account the inherent noise within the
      data. RESULTS: We have produced nucleotide-resolution transcriptome maps that
      identify and differentiate sites of transcription initiation from sites of stable
      RNA processing and mRNA cleavage. Moreover, analysis of these maps provides
      strong evidence for 'pervasive' transcription and shows that contrary to initial
      indications it is not biased towards the production of antisense RNAs. In
      addition, the maps reveal an extensive array of riboswitches, leaderless mRNAs
      and small non-protein-coding RNAs alongside vegetative promoters and post
      transcriptional events, which includes unusual tRNA processing. The
      identification of such features will inform models of complex gene regulation, as
      illustrated here for ribonucleotide reductases and a potential quorum-sensing,
      two-component system. CONCLUSIONS: The approach described here, which is
      transferable to any bacterial species, has produced a step increase in whole-cell
      knowledge of gene regulation in P. acnes. Continued expansion of our maps to
      include transcription associated with different growth conditions and genetic
      backgrounds will provide a new platform from which to computationally model the
      gene expression that determines the physiology of P. acnes and its role in human
      disease.

PMID- 24034788
TI  - Crystal structure of endo-xylogalacturonan hydrolase from Aspergillus
      tubingensis.
AB  - Endo-xylogalacturonan hydrolase is a member of glycoside hydrolase family 28
      (GH28) that hydrolyzes the glycosidic bond between two beta-xylose-substituted
      galacturonic acid residues in pectin. Presented here is the X-ray crystal
      structure of the endo-xylogalacturonan hydrolase from Aspergillus tubingensis
      (XghA) at 1.75 A resolution. The high degree of structural conservation in the
      active site and catalytic apparatus compared with polygalacturonases indicates
      that cleavage of the substrate proceeds in essentially the same way as found for
      the other GH28 enzymes. Molecular modeling of a xylosylated tri-galacturonate in
      the active site identified the amino acid residues involved in substrate binding.
      They border a substrate-binding cleft that is much wider than in other
      polygalacturonases, and can accommodate xylosylated substrates. The most
      extensive interactions appear to occur at subsite +2, in agreement with the
      enzyme kinetics results, which showed enhanced activity on substrates with a
      xylose attached to the galacturonic acid bound at subsite +2. DATABASE:
      Structural data are available in the Protein Data Bank database under accession
      number 4C2L.

PMID- 24034789
TI  - Easy-to-use online referral test detects most patients with a high familial risk
      of colorectal cancer.
AB  - AIM: Currently only 12-30% of individuals with a high risk of Lynch syndrome, the
      most common hereditary colorectal cancer (CRC) syndrome, are referred for genetic
      counselling. We assessed the sensitivity, usability and user experiences of a new
      online referral test aimed at improving referral of high-risk individuals for
      genetic counselling. METHOD: Sensitivity was assessed by entering pedigree data
      from high-risk individuals (i.e. Lynch syndrome mutation carriers) into the
      referral test to determine whether genetic counselling was recommended. For
      usability, we assessed nonmedical staff members' ability to determine referral,
      according to guidelines, in seven fictive clinical cases using the referral test
      after minimal training. Real-life users answered questions about their experience
      with the referral test. RESULT: Sensitivity of the referral test was 91% for
      mutation carriers with CRC (n = 164) and 73% for all affected and nonaffected
      mutation carriers (n = 420). Nonmedical staff members (n = 20) determined
      referral according to guidelines in 84% of cases using the referral test. Ten per
      cent (256/2470) of real-life users provided feedback about experiences; of those,
      71% reported that the referral test increased reassurance, certainty about their
      familial risk and/or certainty about referral. CONCLUSION: The referral test has
      a high sensitivity in detecting individuals with a high risk of Lynch syndrome
      and is suitable for use in clinical practice. Widespread use of the referral test
      should improve cancer prevention in high-risk patients and their relatives.

PMID- 24034791
TI  - Support needs and quality of life in oral cancer: a systematic review.
AB  - PURPOSE: This review aims to systematically review the literature describing
      quality of life (QoL) outcomes and support needs in patients with oral cancer
      along the cancer trajectory. This is needed to form an evidence base for the
      design of interventions that enhance outcomes for this group. METHODS: Six
      electronic databases were searched. The results were screened for eligibility,
      and articles were included if they described patient-reported QoL outcomes that
      were translatable to support needs in patients with oral cancer. Data were
      extracted and synthesized according to the support needs identified and their
      relative impact on QoL. Methodological quality was assessed using the Effective
      Public Health Practice Project (EPHPP) Quality Assessment Tool. RESULTS: Thirty
      one articles met the inclusion criteria. Support needs related to coping with the
      burden of radiotherapy in both psychosocial and physical aspects, swallowing
      dysfunction, dry mouth and oral functional deficits. Issues of depression,
      anxiety and malnutrition were identified as having a significant impact on QoL.
      CONCLUSIONS: Oral cancer support needs are highly subjective and varied in
      severity across the cancer continuum. Support needs that may warrant further
      investigation include management of changes to oral health and functioning,
      swallowing and nutritional compromise and psychological effects of cancer and
      treatment.

PMID- 24034792
TI  - Effectiveness of community health workers delivering preventive interventions for
      maternal and child health in low- and middle-income countries: a systematic
      review.
AB  - BACKGROUND: Community Health Workers are widely utilised in low- and middle
      income countries and may be an important tool in reducing maternal and child
      mortality; however, evidence is lacking on their effectiveness for specific types
      of programmes, specifically programmes of a preventive nature. This review
      reports findings on a systematic review analysing effectiveness of preventive
      interventions delivered by Community Health Workers for Maternal and Child Health
      in low- and middle-income countries. METHODS: A search strategy was developed
      according to the Evidence for Policy and Practice Information and Co-ordinating
      Centre's (EPPI-Centre) guidelines and systematic searching of the following
      databases occurred between June 8-11th, 2012: CINAHL, Embase, Ovid Nursing
      Database, PubMed, Scopus, Web of Science and POPLINE. Google, Google Scholar and
      WHO search engines, as well as relevant systematic reviews and reference lists
      from included articles were also searched. Inclusion criteria were: i) Target
      beneficiaries should be pregnant or recently pregnant women and/or children under
      5 and/or caregivers of children under-5; ii) Interventions were required to be
      preventive and delivered by Community Health Workers at the household level. No
      exclusion criteria were stipulated for comparisons/controls or outcomes. Study
      characteristics of included articles were extracted using a data sheet and a peer
      tested quality assessment. A narrative synthesis of included studies was compiled
      with articles being coded descriptively to synthesise results and draw
      conclusions. RESULTS: A total of 10,281 studies were initially identified and
      through the screening process a total of 17 articles detailing 19 studies were
      included in the review. Studies came from ten different countries and consisted
      of randomized controlled trials, cluster randomized controlled trials, before and
      after, case control and cross sectional studies. Overall quality of evidence was
      found to be moderate. Five main preventive intervention categories emerged:
      malaria prevention, health education, breastfeeding promotion, essential newborn
      care and psychosocial support. All categories showed some evidence for the
      effectiveness of Community Health Workers; however they were found to be
      especially effective in promoting mother-performed strategies (skin to skin care
      and exclusive breastfeeding). CONCLUSIONS: Community Health Workers were shown to
      provide a range of preventive interventions for Maternal and Child Health in low-
      and middle-income countries with some evidence of effective strategies, though
      insufficient evidence is available to draw conclusions for most interventions and
      further research is needed.

PMID- 24034793
TI  - Extracellular membrane vesicles harbouring viral genomes.
AB  - Cells from the three domains of life produce extracellular membrane vesicles
      (MVs), suggesting that MV production is a fundamental aspect of cellular
      physiology. We have recently shown that MVs produced by the hyperthermophilic
      archaeon Thermococcus kodakaraensis can be used as vehicles to transfer exogenous
      recombinant plasmid DNA from cell to cell. Here, we show that Thermococcus
      nautilus, which harbours three plasmids, pTN1, pTN2 and pTN3, produces MVs, and
      that some of them selectively incorporate pTN1 and pTN3. Interestingly, pTN3
      represents the genome of a defective virus, which encodes signature proteins
      common to a large group of viruses infecting hosts from all three cellular
      domains. However, preparations of MVs produced by T. nautilus have a protein
      composition similar to that of classical MVs from Thermococcales and do not
      contain the viral major capsid protein encoded by pTN3. Our results suggest that
      MVs can serve as vehicles for the intercellular transport of viral genomes and
      facilitate recombination between viral, plasmid and/or cellular chromosomes in
      the absence of viral infection. 

PMID- 24034794
TI  - [Duplicate publication: redundant publication or plagiarism?].

PMID- 24034795
TI  - [New anti-angiogenic strategies in the management of kidney cancer].
AB  - INTRODUCTION: The aim of this study was to clarify the current role of adjuvant
      and neo-adjuvant in the treatment of kidney cancer. MATERIALS AND METHODS: The
      data were explored in Medline (http://www.ncbi.nlm.nih.gov) using the following
      MeSH terms or combinations of these keywords: "cancer", "rein", "kidney",
      "adjuvant", "neoadjuvant", "antiangiogenique", "antiangiogenic" and selecting the
      items produced in their methodology, their relevance to the theme explored and
      their date of publication. RESULTS: Thirty-two English and French items published
      between 2001 and 2011 were selected: five studies of evidence level 1, nine level
      2 studies, nine level 4 studies, five studies at level 5 and four literature
      reviews. The cytoreductive nephrectomy as first-line treatment of locally
      advanced or metastatic kidney cancer is now controversial with the advent of new
      targeted anti-angiogenic therapies. In neoadjuvant setting, these treatments
      showed a moderate decrease in tumor volume and rarely improved resectability. In
      adjuvant setting, their place has yet to be specified and several trials are
      currently underway. CONCLUSION: Recent years have seen the anti-angiogenic
      therapeutic strategies upset in locally advanced and metastatic renal cancer. The
      development of clinical trials and research protocols will allow us to determine
      in the near future the optimal therapeutic sequences.

PMID- 24034796
TI  - [Guidelines from the Infectious Disease Committee of the French Association of
      Urology and The Neuro-Urology Committee of the AFU: antibiotic prophylaxis for
      sacral neuromodulation].
AB  - INTRODUCTION: In urology, antibiotic prophylaxis is advised by the French
      Association of anesthesiology (SFAR) and the Infectious Disease Committee of the
      French Association of urology guidelines published in 2010. No guideline exists
      concerning the implantation of neuromodulation implants. MATERIAL AND METHOD: A
      literature analysis was performed on sacral modulation and antibiotic
      prophylaxis. Then guidelines were discussed by reviewers. Items that showed no
      consensus were then discussed again to arrive at recommendations. RESULTS:
      Antibiotic prophylaxis is recommended during the test phase as well as in the
      case of installation of sacral neuromodulation (Grade C). Antibiotic recommended
      (Grade B) are: cefotetan or cefoxitin, 2g dose by slow intravenous injection or
      amoxicillin-clavulanic acid at a dose of 2 g, intravenously or, in the case of
      allergy vancomycin at a dose of 15 mg/kg or the clindamycin has 600 mg
      intravenously. CONCLUSIONS: Despite the lack of high level of evidence,
      antibiotic prophylaxis seems necessary when setting up of electrode case of
      sacral neuromodulation.

PMID- 24034790
TI  - Children followed in the TEDDY study are diagnosed with type 1 diabetes at an
      early stage of disease.
AB  - OBJECTIVE: The Environmental Determinants of Diabetes in the Young (TEDDY) study
      is designed to identify environmental exposures triggering islet autoimmunity and
      type 1 diabetes (T1D) in genetically high-risk children. We describe the first
      100 participants diagnosed with T1D, hypothesizing that (i) they are diagnosed at
      an early stage of disease, (ii) a high proportion are diagnosed by an oral
      glucose tolerance test (OGTT), and (iii) risk for early T1D is related to
      country, population, human leukocyte antigen (HLA)-genotypes and immunological
      markers. METHODS: Autoantibodies to glutamic acid decarboxylase (GADA),
      insulinoma-associated protein 2 (IA-2) and insulin (IAA) were analyzed from 3
      months of age in children with genetic risk. Symptoms and laboratory values at
      diagnosis were obtained and reviewed for ADA criteria. RESULTS: The first 100
      children to develop T1D, 33 first-degree relatives (FDRs), with a median age 2.3
      yr (0.69-6.27), were diagnosed between September 2005 and November 2011. Although
      young, 36% had no symptoms and ketoacidosis was rare (8%). An OGTT diagnosed 9/30
      (30%) children above 3 yr of age but only 4/70 (5.7%) below the age of 3 yr. FDRs
      had higher cumulative incidence than children from the general population (p <
      0.0001). Appearance of all three autoantibodies at seroconversion was associated
      with the most rapid development of T1D (HR = 4.52, p = 0.014), followed by the
      combination of GADA and IAA (HR = 2.82, p < 0.0001). CONCLUSIONS: Close follow-up
      of children with genetic risk enables early detection of T1D. Risk factors for
      rapid development of diabetes in this young population were FDR status and
      initial positivity for GADA, IA-2, and IAA or a combination of GADA and IAA.

PMID- 24034797
TI  - [New ultrasound navigational system in extracorporeal lithotripsy: decreased
      fluoroscopy and radiation].
AB  - PURPOSE: Extracorporeal shock wave lithotripsy is the most common method of
      treatment for kidney stones. Both fluoroscopy and ultrasound imaging can be used
      to locate stones, but fluoroscopy is more frequently employed. Evaluation of a
      new stereotaxic navigational system: the stone was located using an ultrasound
      probe, and its 3D location was saved. The table automatically moved to position
      the stone at the focal point. A real-time follow-up was possible during
      treatment. Our objective was to demonstrate a decrease in the use of fluoroscopy
      to locate kidney stones for extracorporeal shock wave lithotripsy through the use
      of a 3D ultrasound stone locking system. PATIENTS AND METHODS: Prospective
      analysis of the case records of the 20 patients preceding and the 20 patients
      succeeding the arrival of the ultrasound stone locking system Visio-Track (EDAP
      TMS). We used a Student test to compare age, BMI, kidney stone size, number of
      shock waves and administered energy. RESULTS: Patient characteristics were
      comparable. The average age was 55 years old and the average kidney stone size
      was 10.7 mm. Radiation duration was 174.8 seconds in the group without Visio
      Track versus 57.1 seconds in the group with it (P<0.0001). A similar result was
      observed for radiation doses: 5197.25 mGy x cm2 for the group without versus
      1987.6 mGy x cm2 for the group with Visio-Track (P=0.0033). CONCLUSION: The stone
      locking system Visio-Track reduced fluoroscopy in our first group of patients,
      which decreased the patient's individual absorbed irradiation dose.

PMID- 24034798
TI  - [Comparative study of radical prostatectomy versus external beam radiotherapy
      (75.6 Gy) combined with hormone therapy for prostate cancer of intermediate
      D'Amico risk classification].
AB  - INTRODUCTION: Thirty-three percent of the localized cancers belongs initially to
      the group of intermediate risk of D'Amico. The standard treatments validated by
      the French Association of Urology are the radical prostatectomy and the external
      beam radiotherapy. OBJECTIVES: We retrospectively compared the carcinologic
      results of the radical prostatectomy+/-adjuvant treatment (RP) and the external
      beam radiotherapy combining high dose (75.6 Gy) and short hormonotherapy (RH), in
      the treatment of intermediate risk prostate cancer. The series consisted of 143
      patients treated between 2000 and 2006 in the department of Urology and Kidney
      transplantation of the Conception Hospital, Marseilles. The main assessment
      criteria was the survival without biological recurrence (SBR). RESULTS: The
      median follow-up was 90 months [59-51]. The 5 years and 8 years SBR were 85% and
      73% in the RH group, versus 74% and 65% with RP (P=0.196). There was a
      significant difference between the series: on the age of diagnosis (63.9 versus
      73.3 years, P<0.001), the Charlson score of comorbidity (2 versus 3, P<0.001) and
      the number of intermediate criteria per patients (one intermediate criteria: RP
      74% versus 57%, P<0.01). CONCLUSION: According to our study, there was no
      superiority of the radical prostatectomy+/-adjuvant treatment or the external
      radiotherapy combining high dose and concomitant short hormonotherapy on the
      survival without biological recurrence at 5 and 8 years. Many studies confirm
      that a concomitant hormonotherapy increases the carcinologic control, even with a
      high rate external beam radiotherapy.

PMID- 24034799
TI  - [XPS Greenlight photoselective vaporization for benign prostatic hyperplasia:
      analysis of the learning curve and contribution of transrectal ultrasound
      monitoring].
AB  - INTRODUCTION: The aim of this study was to analyze the XPS laser learning curve
      of one single surgeon with no previous experience of PVP and the impact of the
      use of reel time transrectal ultrasound (TRUS) monitoring. MATERIALS AND METHODS:
      Retrospective analysis of the first 100 patients: group 1 (1st-49th patient
      without TRUS) and group 2 (50th-100th with TRUS). The learning curve was analyzed
      through technical variables: vaporization time/intervention time (VT/IT) (%),
      energy delivered (J)/prostate volume (J/mL) and delivered energy (J/s or Watt),
      peroperative conversion into monopolar transurethral resection, postoperative
      complication, duration of catheterization and hospitalization and evolution of
      International Prostate Symptom Score (IPSS), PSA level, prostate residual volume
      and Qmax. Relationships between variables were evaluated by analysing the
      covariance (R 2 software. 14.2). RESULTS: A significant increase in VT/IT
      (P=0.0001) and the energy delivered per mL prostate (P=0.043) was reported in
      group 1. The average energy delivered per second was significantly higher in
      group 2 (P=0.0016). No difference was observed in terms of intra- or
      postoperative complication and catheterization time. The duration of
      hospitalization was significantly shorter in group 2 (P=0.03). The use of TRUS
      was associated with a gain of energy delivered by prostate volume at the end of
      learning curve (P=0.018). Prostate residual volume was significantly lower in the
      group 2 (P=0.0004). CONCLUSION: In our experience, 50 procedures are required to
      achieve the learning curve of PVP. The use of reel time TRUS would increase the
      energy delivered by prostate volume.

PMID- 24034800
TI  - [Laparoscopic approach for artificial urinary sphincter implantation in women
      with severe urinary stress incontinence].
AB  - INTRODUCTION: To evaluate, feasibility, efficacy and morbidity of laparoscopic
      artificial urinary sphincter (AUS) implantation in women with severe stress
      urinary incontinence. PATIENTS AND METHODS: Twenty-six women with severe stress
      urinary incontinence were treated between October 2007 and January 2012 by
      laparoscopic implantation of an AUS AMS 800 (American medical Systems, Inc.,
      Minnetonka, Minnesota). For 18 patients AUS was primary implanted and, for eight,
      AUS was revised for a mechanical failure. Three patients had a concomitant
      laparoscopic vaginal prolapse repair. Mean value was for age 64 years, BMI
      27.8kg/m2, and mean maximal urethral closure pressure was 26.75cm of water. Most
      of the patients (88%) had a history of pelvic or incontinence surgery. The study
      was a retrospective analysis of operative parameters, complications and
      functional results. RESULTS: Three conversions in open surgery and five bladder
      injuries were described. Mean operative time was 149 minutes. Bladder catheter
      was removed at a mean of day 3.8. Mean post-operative stay was 5 days. Early
      postoperative complications consist in eight acute transient urinary retentions,
      two pump migrations, and one vaginal injury. Late post-operative complications
      consist in one vaginal erosion. Explantation of AUS was performed for these last
      two patients. Mean follow-up was 20 months. Sixteen patients are totally
      continent, five have a social continence (1 pad/day) and three need more than one
      pad/day. ANALYSIS: Our results compare favorably to literature either for
      laparoscopic or conventional approach with a limited learning curve. CONCLUSION:
      Laparoscopic implantation of AUS in women with severe stress urinary incontinence
      was feasible and efficient.

PMID- 24034801
TI  - [Post-hysterectomy vesicovaginal fistula].
AB  - OBJECTIVE: Describe the epidemiology, diagnosis and treatment of vesicovaginal
      fistula (VVF). PATIENTS AND METHODS: We conducted a retrospective descriptive
      study of all cases of VVF secondary to hysterectomy. The following parameters
      were studied: age, parity, indication for hysterectomy, risk factors, the
      consultation period, the anatomical type of VVF, the paraclinical, the surgical
      approach and results of the cure. RESULTS: Fourteen cases were identified over 10
      years. All hysterectomies were performed by laparotomia. The average age of
      patients was 54.3+/-13 years. Hysterectomy was performed in view of a uterine
      leiomyoma in eight cases, a cancer of the cervix in four cases, a
      menometrorrhagia in one case and a choriocarcinoma in one case. Four patients had
      received neoadjuvant radiotherapy. The mean time from injury was 13.5+/-18
      months. Examination under valve was allowed to find 11 VVF type 1 and three type
      2 VVF. IVU was normal in seven patients and allowed to find an
      ureterohydronephrose stage III in one patient. VVF was addressed by high in ten
      cases including 5 by transperitoneovaginale and 5 by transvesical pure. The
      postoperative course was uneventful in 11 patients (78%) but marked by
      vesicocutaneous fistula, parietal suppuration and one failure. CONCLUSION: In
      this short series of post-hysterectomy VVF treated by laparotomia, we observed a
      rate of cure satisfying in spite of an important psychosocial morbidity.

PMID- 24034802
TI  - [Bacteriological analysis of more than 600 febrile urinary infections managed in
      a community health network].
AB  - Community-acquired febrile urinary tract infections (UTI) in adult has received
      little attention in the literature. The objective of our study was to determinate
      the distribution of bacterial strains isolated from adults with community
      acquired febrile UTI and antibiotic susceptibility patterns of Escherichia coli.
      PATIENTS AND METHOD: We studied the SPHERES's databank. SPHERES is a Parisian
      medical community network aimed at securing and facilitating the ambulatory
      management of potentially serious acute illnesses. Each patient is included in
      the network according to specific clinical criteria and standardized medical data
      are recorded. We retrospectively studied the medical records of all patients
      treated for a pyelonephritis or a prostatitis between April 2005 and October
      2008. RESULTS: Five hundred and sixty-eight patients were enrolled: 410 women and
      158 men. The overall bacteria's distribution was similar to that observed in
      previous strictly microbiological studies with a more prominent role of E. coli
      (87.5%) to the detriment of other species. The overall susceptibility of E. coli
      to antibiotics recommended in the empiric treatment of pyelonephritis and
      prostatitis was preserved: ciprofloxacin (95.8%), cefotaxime (98%), gentamicin
      (99.4%). In women over 65 years, the susceptibility of E. coli to systemic
      fluoroquinolones fell up 89.7%. This could affect the empiric oral treatment of
      pyelonephritis in older women. CONCLUSIONS: We report the bacterial distribution
      and the resistance pattern of bacteria implicated in febrile urinary infections
      diagnosed and treated in a health network. It seems that E. coli resistance
      increased more in women more than 65 years than in men.

PMID- 24034803
TI  - [Classification of urinary calculi in a pediatric population from Brittany].
AB  - INTRODUCTION: Urinary lithiasis in children is relatively seldom in France as in
      industrialized countries. The determination of their etiology based on their
      composition may lead to a better treatment. METHOD: One hundred and eight urinary
      calculi from 6 months through 18-year-old children were analyzed by using
      spectrophotometry, in order to specify their structure. Six groups were evidenced
      through a multidimensional analysis based on the presence of components weighing
      at least 5% of the total. RESULTS: The youngest children affected were mostly
      boys, and the sex ratio switched after 12.5 years. Above 14 years of age, the
      number of calculi significantly raised. Their composition varied with the gender,
      and their localization with the age. Finally a correlation between infection and
      composition of the calculus was shown in our study. CONCLUSION: The
      classification of calculi among six groups according to their composition, along
      with clinical informations and morphologic studies, has proven its value in
      determining the etiology of the lithiasis. These data help to better understand
      the kind of lithiasis that may be observed and the physiopathology of the
      mechanism explaining it from the gender and age.

PMID- 24034804
TI  - [Intravesical active prostate bleeding diagnosed in B-mode ultrasound].
AB  - Hematuria is one of the most frequent minor complications after prostatic biopsy.
      We would like to report the case of a 68-year-old patient with massive hematuria
      after prostatic biopsy and intravesical active prostate bleeding diagnosed in B
      mode ultrasonography. 

PMID- 24034805
TI  - How to measure oral contraceptive adherence: an ongoing research challenge.

PMID- 24034807
TI  - BetaHCG secretion by a pulmonary adenocarcinoma.
AB  - We report a rare case of metastatic non-small-cell lung cancer in a 43-year-old
      woman with a history of smoking. The tumor secreted human chorionic gonadotropin
      and its beta subunit (BetaHCG). The patient presented with amenorrhea, a positive
      pregnancy test and chest pain. A physical examination and investigations revealed
      no pregnancy, and it was determined that a paraneoplastic syndrome stemming from
      a pulmonary tumor was responsible for the secretion of BetaHCG. This secretion
      decreased with tumor response to chemotherapy. Only a few reports of
      paraneoplastic BetaHCG secretion can be found in the literature for several
      different cancers. 

PMID- 24034808
TI  - Frequent false-positive results of lupus anticoagulant tests in plasmas of
      patients receiving the new oral anticoagulants and enoxaparin.
AB  - INTRODUCTION: Oral direct thrombin and Xa inhibitors are worldwide distributed
      for prevention and treatment of thrombosis. It is important to recognize their
      effects on lupus anticoagulant (LA) testing. The aim of the study is to describe
      the rate of false-positive results of LA tests on plasmas of patients with
      previous negative LA tests results that receive dabigatran etexilate (DAB) 110
      mg/twice a day, rivaroxaban (RIV) 10 mg/day or 15 mg/twice a day, or enoxaparin
      40 mg/day. METHODS: Blood was taken between 1.5 and 4 h post administration.
      Tests evaluated are as follows: prothrombin time, APTT, dilute Russell viper
      venom time (DRVVT) screen, APTT, and DRVVT mixing studies, index of circulating
      anticoagulant (ICA) with normal plasma, screen/confirm normalized ratio (NR) for
      DRVVT and silica clotting time (SCT). RESULTS: Plasmas from patients taking DAB
      (n = 22) presented 100% prolonged APTT and DRVVT with ICA above the cutoff point
      and 81.8% positive screen/confirm NR, 100% prolonged SCT screen, but 4.5%
      positive confirmatory NR. All patients receiving RIV at 15 mg/twice a day (n = 4)
      presented positive DRVVT screen, mixing, and confirmatory tests, 75% and 100%
      prolonged APTT and SCT screen, with negative screen/confirm NR. Those taking RIV
      10 mg/day (n = 22) showed 81.8% prolonged DRVVT screen, 82.3% and 76.5% of them
      with positive mixing and confirmatory studies. Patients receiving enoxaparin also
      presented high prevalence of APTT and DRVVT false-positive results. CONCLUSION:
      Dabigatran etexilate, RIV, and enoxaparin affect tests for LA not only in
      screening and mixing, but also in confirmatory studies. We considered that LA
      testing should not to be performed when patients are taken these drugs,
      particularly if blood is collected at peak, in order to avoid false-positive
      results.

PMID- 24034806
TI  - A statement on abortion by 100 professors of obstetrics: 40 years later.
AB  - In this Journal in 1972, 100 leaders in obstetrics and gynecology published a
      compelling statement that recognized the legalization of abortion in several
      states and anticipated the 1973 Supreme Court decision in Roe v Wade. They
      projected the numbers of legal abortions that likely would be required by women
      in the United States and described the role of the teaching hospital in meeting
      that responsibility. They wrote to express their concern for women's health in a
      new legal and medical era of reproductive control and to define the
      responsibilities of academic obstetrician-gynecologists. Forty years later, 100
      professors examine the statement of their predecessors in light of medical
      advances and legal changes and suggest a further course of action for
      obstetrician gynecologists. 

PMID- 24034810
TI  - Short-term psychotherapeutic treatment in adolescents engaging in non-suicidal
      self-injury: a randomized controlled trial.
AB  - BACKGROUND: Worldwide, prevalence rates of adolescent non-suicidal self-injury
      (NSSI) range between 13 and 45%. In Germany, lifetime prevalence of NSSI is
      around 25% in non-clinical samples, and the one-year prevalence for repetitive
      NSSI is 4%. NSSI is present in the context of several axis I and II disorders
      (for example, affective disorders or borderline personality disorder); however,
      preliminary evidence suggests that it would be justified to consider NSSI as its
      own diagnostic category. Despite the large impact of this behavior, there is
      still a lack of evidence-based, specific, and effective manualized treatment
      approaches for adolescents with NSSI. METHODS/DESIGN: The study is designed as a
      randomized controlled trial (RCT) to test the effectiveness of a new cognitive
      behavioral treatment manual for self-harming adolescents - the 'Cutting-Down
      Programme' (CDP). A total of 80 adolescents aged between 12 and 17 years from a
      region in Southern Germany who have engaged in repetitive NSSI (>=5 incidents) in
      the last 6 months will be randomized into a treatment group (CDP) or a control
      group that will receive treatment as usual (TAU). The adolescents will be
      assessed by means of structured interviews and questionnaires at three time
      points (before treatment, directly after treatment and six months after
      treatment). Primary outcome criterion is a significant reduction (or remission)
      in the frequency of NSSI. Secondary outcome criteria are depressivity as well as
      general well-being and self-worth. Additionally, comorbid psychiatric disorders
      and childhood adversity will be evaluated as predictors of therapeutic outcome.
      DISCUSSION: Recently, a pilot study in the United Kingdom showed significant
      reductions in self-harming behavior, depressive symptoms and trait anxiety. This
      is the first RCT to test the effectiveness of a short-term psychotherapeutic
      intervention in outpatients engaging in NSSI. TRIAL REGISTRATION: The study is
      registered in the German Clinical Trials Register DRKS00003605.

PMID- 24034811
TI  - Methylation profiling and evaluation of demethylating therapy in renal cell
      carcinoma.
AB  - BACKGROUND: Despite therapeutic advances in targeted therapy, metastatic renal
      cell carcinoma (RCC) remains incurable for the vast majority of patients. Key
      molecular events in the pathogenesis of RCC include inactivation of the VHL
      tumour suppressor gene (TSG), inactivation of chromosome 3p TSGs implicated in
      chromatin modification and remodelling and de novo tumour-specific promoter
      methylation of renal TSGs. In the light of these observations it can be proposed
      that, as in some haematological malignancies, demethylating agents such as
      azacitidine might be beneficial for the treatment of advanced RCC. RESULTS: Here
      we report that the treatment of RCC cell lines with azacitidine suppressed cell
      proliferation in all 15 lines tested. A marked response to azacitidine therapy
      (>50% reduction in colony formation assay) was detected in the three cell lines
      with VHL promoter methylation but some RCC cell lines without VHL TSG methylation
      also demonstrated a similar response suggesting that multiple methylated TSGs
      might determine the response to demethylating therapies. To identify novel
      candidate methylated TSGs implicated in RCC we undertook a combined analysis of
      copy number and CpG methylation array data. Candidate novel epigenetically
      inactivated TSGs were further prioritised by expression analysis of RCC cell
      lines pre and post-azacitidine therapy and comparative expression analysis of
      tumour/normal pairs. Thus, with subsequent investigation two candidate genes were
      found to be methylated in more than 25% of our series and in the TCGA methylation
      dataset for 199 RCC samples: RGS7 (25.6% and 35.2% of tumours respectively) and
      NEFM in (25.6% and 30.2%). In addition three candidate genes were methylated in
      >10% of both datasets (TMEM74 (15.4% and 14.6%), GCM2 (41.0% and 14.6%) and AEBP1
      (30.8% and 13.1%)). Methylation of GCM2 (P = 0.0324), NEFM (P = 0.0024) and RGS7
      (P = 0.0067) was associated with prognosis. CONCLUSIONS: These findings provide
      preclinical evidence that treatment with demethylating agents such as azacitidine
      might be useful for the treatment of advanced RCC and further insights into the
      role of epigenetic changes in the pathogenesis of RCC.

PMID- 24034813
TI  - Perceptions of veterinarians in bovine practice and producers with beef cow-calf
      operations enrolled in the US Voluntary Bovine Johne's Disease Control Program
      concerning economic losses associated with Johne's disease.
AB  - This study compares the perceptions of producers and veterinarians on the
      economic impacts of Mycobacterium avium subspecies paratuberculosis (MAP)
      infection in cow-calf herds. Questionnaires were mailed to beef producers through
      the Designated Johne's Coordinators and to veterinarians belonging to a
      nationwide professional organization. Important components of losses associated
      with MAP infected cows were used to estimate total loss per infected cow-year
      using an iterative approach based on collected survey data. Veterinarians were
      more likely to perceive a lower calving percentage in MAP infected cows compared
      to producers (P=0.02). Income lost due to the presence of Johne's disease (JD) in
      an infected cattle herd was perceived to be higher by veterinarians (P<0.01).
      Compared to veterinarians without JD certification, seedstock producers were more
      likely to perceive genetic losses due to culling cows positive for MAP (P<0.01).
      There were mixed opinions regarding the magnitude of lowered weaning weight in
      calves from infected cows and perceived differences in risk of other diseases or
      conditions in infected cows. An annual loss of $235 (95% CR: $89-$457) for each
      infected animal was estimated based on information from the producer survey. The
      analogous estimate using information inputs from veterinarians was $250 ($82
      $486). Mean annual loss due to JD in a 100 cow herd with a 7% true prevalence was
      $1644 ($625-$3250) based on information provided by producers. Similarly, mean
      annual loss based on information collected from veterinarians was $1747 ($575
      $3375). 

PMID- 24034812
TI  - Leaf cDNA-AFLP analysis of two citrus species differing in manganese tolerance in
      response to long-term manganese-toxicity.
AB  - BACKGROUND: Very little is known about manganese (Mn)-toxicity-responsive genes
      in citrus plants. Seedlings of 'Xuegan' (Citrus sinensis) and 'Sour pummelo'
      (Citrus grandis) were irrigated for 17 weeks with nutrient solution containing 2
      MUM (control) or 600 MUM (Mn-toxicity) MnSO4. The objectives of this study were
      to understand the mechanisms of citrus Mn-tolerance and to identify
      differentially expressed genes, which might be involved in Mn-tolerance. RESULTS:
      Under Mn-toxicity, the majority of Mn in seedlings was retained in the roots; C.
      sinensis seedlings accumulated more Mn in roots and less Mn in shoots (leaves)
      than C. grandis ones and Mn concentration was lower in Mn-toxicity C. sinensis
      leaves compared to Mn-toxicity C. grandis ones. Mn-toxicity affected C. grandis
      seedling growth, leaf CO2 assimilation, total soluble concentration, phosphorus
      (P) and magenisum (Mg) more than C. sinensis. Using cDNA-AFLP, we isolated 42 up
      regulated and 80 down-regulated genes in Mn-toxicity C. grandis leaves. They were
      grouped into the following functional categories: biological regulation and
      signal transduction, carbohydrate and energy metabolism, nucleic acid metabolism,
      protein metabolism, lipid metabolism, cell wall metabolism, stress responses and
      cell transport. However, only 7 up-regulated and 8 down-regulated genes were
      identified in Mn-toxicity C. sinensis ones. The responses of C. grandis leaves to
      Mn-toxicity might include following several aspects: (1) accelerating leaf
      senescence; (2) activating the metabolic pathway related to ATPase synthesis and
      reducing power production; (3) decreasing cell transport; (4) inhibiting protein
      and nucleic acid metabolisms; (5) impairing the formation of cell wall; and (6)
      triggering multiple signal transduction pathways. We also identified many new Mn
      toxicity-responsive genes involved in biological and signal transduction,
      carbohydrate and protein metabolisms, stress responses and cell transport.
      CONCLUSIONS: Our results demonstrated that C. sinensis was more tolerant to Mn
      toxicity than C. grandis, and that Mn-toxicity affected gene expression far less
      in C. sinensis leaves. This might be associated with more Mn accumulation in
      roots and less Mn accumulation in leaves of Mn-toxicity C. sinensis seedlings
      than those of C. grandis seedlings. Our findings increase our understanding of
      the molecular mechanisms involved in the responses of plants to Mn-toxicity.

PMID- 24034814
TI  - Mathematical model of the 2010 foot-and-mouth disease epidemic in Japan and
      evaluation of control measures.
AB  - A large-scale foot-and-mouth disease (FMD) epidemic occurred in Japan in 2010.
      The epidemic arose in an area densely populated with cattle and pigs, continued
      for 3 months, and was contained by emergency vaccination. In this study, a
      mathematical simulation model of FMD transmission between farms was developed to
      generate the disease spread in the affected area. First, a farm-distance-based
      transmission kernel was estimated using the epidemic data. The estimated
      transmission kernel was then incorporated into the transmission model to evaluate
      the effectiveness of several control measures. The baseline model provided a good
      fit to the observed data during the period from imposition of movement
      restrictions until the implementation of vaccination. Our simulation results
      demonstrated that prompt culling on infected farms after detection could
      contribute to reducing the disease spread. The number of infected farms decreased
      to 30% of the baseline model by applying the 24-h prompt culling scenario. The
      early detection scenario resulted in a smaller-sized epidemic. However, the
      results of this scenario included a 35% chance of large-scale epidemic (more than
      500 infected farms), even when the disease was detected 14 days earlier than in
      the baseline model. As additional options, preemptive culling could halt the
      epidemic more effectively. However, the preemptive culling scenario required
      substantial resources for culling operations. The 1-km preemptive scenario
      involved more than 50 farms remaining to be culled per day. Therefore, preemptive
      culling scenarios accompanied some difficulties in maintaining a sufficient
      capacity for culling in the affected area. A 10-km vaccination 7 days after the
      first detection of the disease demonstrated the potential to contain the epidemic
      to a small scale, while implementation of a 3-km vaccination on the same day
      could not effectively reduce epidemic size. In vaccination scenarios, the total
      number of farms that were either culled or vaccinated exceeded that of the
      baseline model. Vaccination scenarios therefore posed a problem of appropriate
      management of many vaccinated animals, whether these vaccinated animals would be
      culled or not. The present FMD transmission model developed using the 2010 FMD
      epidemic data in Japan provides useful information for consideration of suitable
      control strategies against FMD. 

PMID- 24034815
TI  - Can early host responses to mycobacterial infection predict eventual disease
      outcomes?
AB  - Diagnostic tests used for Johne's disease in sheep either have poor sensitivity
      and specificity or only detect disease in later stages of infection. Predicting
      which of the infected sheep are likely to become infectious later in life is
      currently not feasible and continues to be a major hindrance in disease control.
      We conducted this longitudinal study to investigate if a suite of diagnostic
      tests conducted in Mycobacterium avium subspecies paratuberculosis (MAP) exposed
      lambs at 4 months post infection can accurately predict their clinical status at
      12 months post infection. We tracked cellular and humoral responses and quantity
      of MAP shedding for up to 12 months post challenge in 20 controls and 37 exposed
      sheep. Infection was defined at necropsy by tissue culture and disease spectrum
      by lesion type. Data were analysed using univariable and multivariable logistic
      regression models and a subset of variables from the earliest period post
      inoculation (4 months) was selected for predicting disease outcomes later on (12
      months). Sensitivity and specificity of tests and their combinations in series
      and parallel were determined. Early elevation in faecal MAP DNA quantity and a
      lower interferon gamma (IFNgamma) response were significantly associated with
      sheep becoming infectious as well as progressing to severe disease. Conversely,
      early low faecal MAP DNA and higher interleukin-10 responses were significantly
      associated with an exposed animal developing protective immunity. Combination of
      early elevated faecal MAP DNA or lower IFNgamma response had the highest
      sensitivity (75%) and specificity (81%) for identifying sheep that would become
      infectious. Collectively, these results highlight the potential for combined test
      interpretation to aid in the early prediction of sheep susceptibility to MAP
      infection. 

PMID- 24034816
TI  - New types of experimental data shape the use of enzyme kinetics for dynamic
      network modeling.
AB  - Since the publication of Leonor Michaelis and Maude Menten's paper on the
      reaction kinetics of the enzyme invertase in 1913, molecular biology has evolved
      tremendously. New measurement techniques allow in vivo characterization of the
      whole genome, proteome or transcriptome of cells, whereas the classical enzyme
      essay only allows determination of the two Michaelis-Menten parameters V and
      K(m). Nevertheless, Michaelis-Menten kinetics are still commonly used, not only
      in the in vitro context of enzyme characterization but also as a rate law for
      enzymatic reactions in larger biochemical reaction networks. In this review, we
      give an overview of the historical development of kinetic rate laws originating
      from Michaelis-Menten kinetics over the past 100 years. Furthermore, we briefly
      summarize the experimental techniques used for the characterization of enzymes,
      and discuss web resources that systematically store kinetic parameters and
      related information. Finally, describe the novel opportunities that arise from
      using these data in dynamic mathematical modeling. In this framework, traditional
      in vitro approaches may be combined with modern genome-scale measurements to
      foster thorough understanding of the underlying complex mechanisms.

PMID- 24034817
TI  - Medical malpractice claims in relation to colorectal malignancy in the national
      health service.
AB  - AIM: Under the current increased financial constraints affecting the National
      Health Service (NHS), clinical negligence claims and associated compensations are
      constantly rising. Our aim was to identify the magnitude, trends and causes of
      malpractice claims in relation to a common pathology such as colorectal
      malignancy in the NHS. METHOD: Data requests were submitted to the NHS Litigation
      Authority (NHSLA) and to the Medical Defence Union (MDU) and Medical Protection
      Society (MPS). Data were reviewed, categorized clinically and analysed in terms
      of causes and costs behind claims. RESULTS: Data from the MPS and MDU were
      unavailable. In all, 169 claims were identified from the NHSLA database between
      2003 and 2012; 123 (73%) cases had been closed, 80 (65%) of which were
      successful. An increasing overall claim frequency and success rate were found
      over the last few years. Total litigation expenses were L8.6 million, with 39%
      paid out as legal expenses. The commonest cause of complaint in successful claims
      was in relation to diagnostic delays or failures (58%, L5.1 million), with a
      delay or failure by the clinician to take action in response to an abnormal
      investigation result being a major factor. The occurrence of peri-operative
      complications (20%, L1.6 million) was the second commonest cause. CONCLUSION:
      Average frequency and success rates of malpractice claims in secondary care in
      the NHS are rising, leading to significant overall payouts. The failure or delay
      in diagnosing colorectal malignancy or its postoperative complications is a
      common cause behind malpractice claims. Improvement in these areas could enhance
      patient care and reduce future claims.

PMID- 24034818
TI  - Clinical and radiological impact of liver transplantation for brain in cirrhosis
      patients without hepatic encephalopathy.
AB  - OBJECTIVE: To elucidate the effect of liver transplantation (LT) on brain
      dysfunctions in cirrhotic patients who had no clinical evidence of hepatic
      encephalopathy (HE), we performed a prospective study of voxel-based diffusion
      tensor imaging (DTI) and detailed cognitive examination. METHODS: We assessed 12
      consecutive patients as transplant candidates by DTI, with neurological and
      cognitive examinations just before and at 6 months after LT. RESULTS: After LT,
      cirrhotic patients showed significant improvement in visual reproduction, digit
      symbol, digit span, Stroop test, and Trail-making test scores, suggesting
      recovery of frontal-temporal function. As for voxel-based DTI, increased mean
      diffusivity (MD) and reduced fractional anisotropy (FA) values were found before
      LT in the frontal and temporal lobes of cirrhotic patients. After LT, the unusual
      FA and MD values observed in the frontal and temporal lobes preoperatively were
      significantly reduced. CONCLUSION: End-stage cirrhotic patients without clinical
      evidence of HE showed increased MD and decreased FA values in both frontal and
      temporal lobes. These parameters improved after LT, in line with cognitive
      function. MD and FA values might be of value as a biomarker in end-stage
      cirrhotic patients for investigating brain tissue dysfunctions and evaluating the
      efficacy of LT.

PMID- 24034819
TI  - Increased ventriculostomy infection rate with use of intraventricular tissue
      plasminogen activator: a single-center observation.
AB  - OBJECTIVE: Intraventricular tissue plasminogen activator (alteplase) has been
      advocated for prevention of vasospasm in aneurysmal subarachnoid hemorrhage and
      treatment of traumatic or spontaneous intraventricular hemorrhage. External
      ventricular drain (EVD) insertion is often performed to manage increased
      intracranial pressure and hydrocephalus associated with these disease states. EVD
      related ventriculitis is a serious infection with an up to 50% mortality rate.
      METHODS: We assessed the EVD infection rate in patients receiving
      intraventricular alteplase over a 12-month period. Patients were divided into
      intraventricular alteplase and non-intraventricular alteplase groups;
      ventriculitis rates were compared. RESULTS: EVDs were placed in 93 patients. Six
      of 7 (86%) patients who received intraventricular alteplase developed
      ventriculitis versus 4 of 86 (5%) patients in the non-intraventricular alteplase
      group (p<0.0001). CONCLUSION: Intraventricular alteplase use may increase
      ventriculitis risk. Currently, we reserve intraventricular alteplase for patients
      with EVDs obstructed by hematoma accompanied by increased intracranial pressure.

PMID- 24034820
TI  - A ruptured infectious intracranial aneurysm with a combined fungal and bacterial
      etiology.

PMID- 24034821
TI  - Factors associated with self-reported use of mouthwashes in southern Brazil in
      1996 and 2009.
AB  - OBJECTIVE: To evaluate the association between sociodemographic factors and self
      reported use of mouthwashes in a city in the south of Brazil over a time span of
      13 years. METHODS: The study involves a comparison of two household surveys
      conducted in 1996 and 2009. Respectively, 850 and 982 households were included in
      each year. The mother of the family answered to a structured questionnaire to
      provide sociodemographic data. Self-reported use of mouthwash was evaluated in a
      binary manner (yes/no). Multivariate Poisson regression models were used to
      estimate proportion ratios (PR) and 95% confidence intervals (95% CI). RESULTS:
      The proportion of mouthwash use increased significantly from 10.8% to 24.2% after
      13 years. The probability of using mouthwashes increased more than two times from
      1996 to 2009 (PR = 2.25 95% CI 1.80-2.82). Higher probabilities for using
      mouthwashes were observed in households with higher income (PR = 2.63 95% CI 1.97
      3.51) and in those households where the mothers had higher educational levels (PR
      = 1.46 95% CI 1.05-2.03). CONCLUSION: Higher family income and higher maternal
      educational level were associated with self-reported use of mouthwashes in a
      higher proportion of households.

PMID- 24034823
TI  - Cd-doped ZnO quantum dots-based immunoassay for the quantitative determination of
      bisphenol A.
AB  - Bisphenol A (BPA) is a ubiquitous environmental contaminant in food products and
      aquatic ecosystems. Its endocrine and developmental toxicity presents a serious
      concern to human health and an effective high-throughput method for its detection
      is desirable. In this paper, water-soluble quantum dots (QDs) have been
      conjugated covalently with BPA antibodies and the conjugate has been utilized in
      a competitive fluorescence-linked immunoassay (FLISA). Cd-doped ZnO QDs were
      functionalized with poly(amidoamine) (PAMAM) dendrimers, as evidenced by
      ultraviolet absorption spectrum and fluorescence emission spectra analyses, and
      this led to their successful transfer into aqueous solution. Biological mass
      spectrometry demonstrated that the bisphenol A antibodies were successfully
      coupled to the water-soluble QDs, and the structures of these conjugates kept
      intact. The FLISA method allowed for BPA determination in a linear working range
      of 20.8-330.3 ng mL(-1) with the limit of detection (LOD) of 13.1 ng mL(-1). The
      recoveries of BPA from water samples were from 85.92% to 109.62%. In conclusion,
      a rapid and sensitive FLISA was developed by utilizing novel QD coupling method
      and validated for use in aqueous samples.

PMID- 24034822
TI  - Physical and mental health perspectives of first year undergraduate rural
      university students.
AB  - BACKGROUND: University students are often perceived to have a privileged position
      in society and considered immune to ill-health and disability. There is growing
      evidence that a sizeable proportion experience poor physical health, and that the
      prevalence of psychological disorders is higher in university students than their
      community peers. This study examined the physical and mental health issues for
      first year Australian rural university students and their perception of access to
      available health and support services. METHODS: Cross-sectional study design
      using an online survey form based on the Adolescent Screening Questionnaire
      modeled on the internationally recognised HEADSS survey tool. The target audience
      was all first-year undergraduate students enrolled in an on-campus degree
      program. The response rate was 41% comprising 355 students (244 females, 111
      males). Data was analysed using standard statistical techniques including
      descriptive and inferential statistics; and thematic analysis of the open-ended
      responses. RESULTS: The mean age of the respondents was 20.2 years (SD 4.8). The
      majority of the students lived in on-campus residential college style
      accommodation, and a third combined part-time paid work with full-time study.
      Most students reported being in good physical health. However, on average two
      health conditions were reported over the past six months, with the most common
      being fatigue (56%), frequent headaches (26%) and allergies (24%). Mental health
      problems included anxiety (25%), coping difficulties (19.7%) and diagnosed
      depression (8%). Most respondents reported adequate access to medical doctors and
      support services for themselves (82%) and friends (78%). However the qualitative
      comments highlighted concerns about stigma, privacy and anonymity in seeking
      counselling. CONCLUSIONS: The present study adds to the limited literature of
      physical and mental health issues as well as barriers to service utilization by
      rural university students. It provides useful baseline data for the development
      of customised support programs at rural campuses. Future research using a
      longitudinal research design and multi-site studies are recommended to facilitate
      a deeper understanding of health issues affecting rural university students.

PMID- 24034824
TI  - Zebrafish embryos/larvae for rapid determination of effects on hypothalamic
      pituitary-thyroid (HPT) and hypothalamic-pituitary-interrenal (HPI) axis: mRNA
      expression.
AB  - To identify and prioritize chemicals that may affect thyroid and
      adrenal/interregnal endocrine system and to reduce cost and animal use by
      conventional toxicity assay, an in vivo screening assay was developed using
      zebrafish embryos/larvae based on measurement of expression of genes that were
      suggested to play important roles in hypothalamic-pituitary-thyroid (HPT) and
      hypothalamic-pituitary-interrenal (HPI) axis. Model chemicals that could modulate
      HPT and HPI axis in adult fish were selected in assay validation, including anti
      thyroid agent 6-Propyl-2-thiouracil (PTU) and cytochrome P450 11B (Cyp11b) enzyme
      inhibitor metyrapone (MET). Zebrafish embryos were exposed to different
      concentrations of model chemical from 4h post-fertilization (hpf) to 5d post
      fertilization (dpf). Exposure to PTU increased mRNA expression of sodium iodide
      symporter (nis) and thyroglobulin (tg) involved in HPT axis, and MET treatment up
      regulated all the mRNA expression tested involved in HPI axis by a compensatory
      mechanism. These results suggested that HPT and HPI axis were active upon
      chemical exposure at least at 5 dpf zebrafish. Furthermore, we studied the
      effects of PTU or MET on the cross-talk between HPT and HPI axis. The results
      demonstrated that PTU and MET could affect cross-talk responses in zebrafish
      embryos/larvae.

PMID- 24034825
TI  - Photo-dissociation of dimethylamine by KrBr* excilamp.
AB  - A study of dimethylamine photo-dissociation in the gas phase has been conducted
      using UV radiation delivered from a KrBr(*) excilamp, driven by a sinusoidal
      electronic control gear with maximum emission at wavelength of 207 nm. The
      electrical input power and radiant power of the lamp were measured to determine
      their effects on the degradation. The influence of flow velocity and initial
      concentration of dimethylamine were also examined. In order to evaluate the photo
      dissociation process comprehensively, several parameters were investigated,
      including removal efficiency, energy yield, carbon balance and CO2 selectivity.
      It is shown that the removal efficiency increases with enhanced input power and
      decreased gas flow rate. A high removal efficiency of 68% is achieved for lamp
      power 102W and flow velocity 15 m(3) h(-1). The optimum dimethylamine initial
      concentration is around 3520 mg m(-3), for which the energy yield reaches up to
      442 gk Wh(-1) when the input power is 65W. In addition, two chain compounds (1,3
      bis-dimethylamino-2-propanol; 3-penten-2-one, 4-amino) and three ring organic
      matters (1-azetidinecarboxaldehyde, 2,2,4,4-tetramethyl; N-m-tolyl-succinamic
      acid; p-acetoacetanisidide), were identified by GC-MS as secondary products, in
      order to demonstrate the pathways of the dimethylamine degradation.

PMID- 24034826
TI  - A proposal for a diet-based local PCDD/F deposition limit.
AB  - This study proposes a method to estimate the maximal tolerable value for the
      atmospheric deposition of dioxins (PCDD/Fs) to soil. The case study for the
      application of this methodology is an Alpine valley where a steel production
      plant is present. In order to estimate the limit value for the PCDD/F deposition,
      consolidated food chain models were applied, but were adapted to be run backwards
      with respect to their original formulation, by starting from the diet of people
      living in the region and from the PCDD/F Tolerable Daily Intake value proposed by
      the World Health Organization. For this case study, the estimated limit value was
      2.30 pg WHO-TEQ m(-2) d(-1) when only local diary products were taken into
      account and 1.91 pg WHO-TEQ m(-2) d(-1) when also the role of local cereals and
      vegetables was considered. The average PCDD/F deposition measured in the same
      region during a monitoring campaign was lower than the above limit values (1.40
      pg WHO-TEQ m(-2) d(-1)). Indications on how to consider the contribution of meat
      and fish are provided too. The approach proposed in this paper represents a
      useful tool to assess the acceptable overall deposition for a specific region.

PMID- 24034827
TI  - Matrix effect on the performance of headspace solid phase microextraction method
      for the analysis of target volatile organic compounds (VOCs) in environmental
      samples.
AB  - Solid phase microextraction (SPME) is a fast, cheap and solvent free methodology
      widely used for environmental analysis. A SPME methodology has been optimized for
      the analysis of VOCs in a range of matrices covering different soils of varying
      textures, organic matrices from manures and composts from different origins, and
      biochars. The performance of the technique was compared for the different
      matrices spiked with a multicomponent VOC mixture, selected to cover different
      VOC groups of environmental relevance (ketone, terpene, alcohol, aliphatic
      hydrocarbons and alkylbenzenes). VOC recovery was dependent on the nature itself
      of the VOC and the matrix characteristics. The SPME analysis of non-polar
      compounds, such as alkylbenzenes, terpenes and aliphatic hydrocarbons, was
      markedly affected by the type of matrix as a consequence of the competition for
      the adsorption sites in the SPME fiber. These non-polar compounds were strongly
      retained in the biochar surfaces limiting the use of SPME for this type of
      matrices. However, this adsorption capacity was not evident when biochar had
      undergone a weathering/aging process through composting. Polar compounds (alcohol
      and ketone) showed a similar behavior in all matrices, as a consequence of the
      hydrophilic characteristics, affected by water content in the matrix. SPME showed
      a good performance for soils and organic matrices especially for non-polar
      compounds, achieving a limit of detection (LD) and limit of quantification (LQ)
      of 0.02 and 0.03 ng g(-1) for non-polar compounds and poor extraction for more
      hydrophilic and polar compounds (LD and LQ higher 310 and 490 ng g(-1)). The
      characteristics of the matrix, especially pH and organic matter, had a marked
      impact on SPME, due to the competition of the analytes for active sites in the
      fiber, but VOC biodegradation should not be discarded in matrices with active
      microbial biomass.

PMID- 24034828
TI  - Determination of anti-anxiety and anti-epileptic drugs in hospital effluent and a
      preliminary risk assessment.
AB  - In this study, an analytical methodology was developed for the determination of
      psycho-active drugs in the treated effluent of the University Hospital at the
      Federal University of Santa Maria, RS - Brazil. Samples were collected from point
      A (Emergency) and point B (General effluent). The adopted methodology included a
      pre-concentration procedure involving the use of solid phase extraction and
      determination by liquid chromatography coupled to mass spectrometry. The limit of
      detection for bromazepam and lorazepam was 4.9 +/- 1.0 ng L(-1) and, for
      carbamazepine, clonazepam and diazepam was 6.1 +/- 1.5 ng L(-1). The limit of
      quantification was 30.0 +/- 1.1 ng L(-1), for bromazepam, clonazepam and
      lorazepam; for carbamazepine was 50.0 +/- 1.8 ng L(-1) and was 40.0 +/- 1.0 ng L(
      1) for diazepam. The mean concentrations in the Emergency and General effluent
      treated currents were as follows: for bromazepam, 195 +/- 6 ng L(-1) and 137 +/-
      7 ng L(-1); for carbamazepine, 590 +/- 6 ng L(-1) and 461 +/- 10 ng L(-1); for
      diazepam, 645 +/- 1 ng L(-1) and 571 +/- 10 ng L(-1); for lorazepam, 96 +/- 7 ng
      L(-1) and 42 +/- 4 ng L(-1); and for clonazepam, 134 +/- 10 ng L(-1) and 57 +/-
      10 ng L(-1). A preliminary risk assessment was conducted: carbamazepine and
      diazepam require considerable attention owing to their environmental toxicity.
      The occurrence of these psychoactive-drugs and the environmental risks that they
      pose demonstrated the need for a more efficient treatment system. As far we are
      aware, there have been no comparable studies to this on the hazards of hospital
      effluents in Brazil, and very few that have carried out a risk assessment of
      psycho-active drugs in hospital effluent in general.

PMID- 24034829
TI  - Analytical modeling of the subsurface volatile organic vapor concentration in
      vapor intrusion.
AB  - The inhalation of volatile and semi-volatile organic compounds that intrude from
      a subsurface contaminant source into indoor air has become the subject of health
      and safety concerns over the last twenty years. Building subslab and soil gas
      contaminant vapor concentration sampling have become integral parts of vapor
      intrusion field investigations. While numerical models can be of use in analyzing
      field data and in helping understand the subslab and soil gas vapor
      concentrations, they are not widely used due to the perceived effort in setting
      them up. In this manuscript, we present a new closed-form analytical expression
      describing subsurface contaminant vapor concentrations, including subslab vapor
      concentrations. The expression was derived using Schwarz-Christoffel mapping.
      Results from this analytical model match well the numerical modeling results.
      This manuscript also explores the relationship between subslab and exterior soil
      gas vapor concentrations, and offers insights on what parameters need to receive
      greater focus in field studies. 

PMID- 24034830
TI  - Dendrochemical patterns of calcium, zinc, and potassium related to internal
      factors detected by energy dispersive X-ray fluorescence (EDXRF).
AB  - Energy dispersive X-ray fluorescence (EDXRF) provides highly sensitive and
      precise spatial resolution of cation content in individual annual growth rings in
      trees. The sensitivity and precision have prompted successful applications to
      forensic dendrochemistry and the timing of environmental releases of
      contaminants. These applications have highlighted the need to distinguish
      dendrochemical effects of internal processes from environmental contamination.
      Calcium, potassium, and zinc are three marker cations that illustrate the
      influence of these processes. We found changes in cation chemistry in tree rings
      potentially due to biomineralization, development of cracks or checks,
      heartwood/sapwood differentiation, intra-annual processes, and
      compartmentalization of infection. Distinguishing internal from external
      processes that affect dendrochemistry will enhance the value of EDXRF for both
      physiological and forensic investigations.

PMID- 24034831
TI  - Degradation kinetics and chloropicrin formation during aqueous chlorination of
      dinoseb.
AB  - The kinetics of chlorination of dinoseb and the corresponding formation of
      disinfection by-products (DBPs) were studied between pH 4 and 9 at room
      temperature (25+/-1 degrees C). The reactivity shows a minimum at pH 9, a maximum
      at pH 4 and a medium at neutral conditions. pH profile of the apparent second
      order rate constant of the reaction of dinoseb with chlorine was modeled
      considering the elementary reactions of HOCl with dinoseb species and an acid
      catalyzed reaction. The predominant reactions at near neutral pH were the
      reactions of HOCl with the two species of dinoseb. The rate constants of 2.0 (+/
      0.8)*10(4)M(-2)s(-1), 3.3 (+/-0.6) and 0.5 (+/-0.1)M(-1)s(-1) were determined for
      the acid-catalyzed reaction, HOCl reacted with dinoseb and dinoseb(-),
      respectively. The main degradation by-products of the dinoseb formed during
      chlorination have been separated and identified by GC-MS with liquid-liquid
      extraction sample pretreatment. Six volatile and semi-volatile DBPs were
      identified in the chlorination products, including chloroform (CF),
      monochloroacetone, chloropicrin (TCNM), 1,1-dichloro-2-methy-butane, 1,2-dichloro
      2-methy-butane, 1-chloro-3-methy-pentanone. A proposed degradation pathway of
      dinoseb during chlorination was then given. TCNM and CF formation potential
      during chlorination of dinoseb reached as high as 0.077 and 0.097MUMMUM(-1)
      dinoseb under the traditional condition (pH=7 and Cl2/C=2). Their yields varied
      with Cl2/C, pH and time. The maximum yields of TCNM appeared at molar ratio as
      Cl2/C=1 and pH 3, while the maximum of CF appeared at molar ratio as Cl2/C=4 and
      pH 7. [TCNM]/[CF] decreased with reaction time and increased solution pH. 

PMID- 24034832
TI  - The impact of maternal obesity on intrapartum outcomes in otherwise low risk
      women: secondary analysis of the Birthplace national prospective cohort study.
AB  - OBJECTIVES: To evaluate the impact of maternal BMI on intrapartum interventions
      and adverse outcomes that may influence choice of planned birth setting in
      healthy women without additional risk factors. DESIGN: Prospective cohort study.
      SETTING: Stratified random sample of English obstetric units. SAMPLE: 17,230
      women without medical or obstetric risk factors other than obesity. METHODS:
      Multivariable log Poisson regression was used to evaluate the effect of BMI on
      risk of intrapartum interventions and adverse maternal and perinatal outcomes
      adjusted for maternal characteristics. MAIN OUTCOME MEASURES: Maternal
      intervention or adverse outcomes requiring obstetric care (composite of:
      augmentation, instrumental delivery, intrapartum caesarean section, general
      anaesthesia, blood transfusion, 3rd/4th degree perineal tear); neonatal unit
      admission or perinatal death. RESULTS: In otherwise healthy women, obesity was
      associated with an increased risk of augmentation, intrapartum caesarean section
      and some adverse maternal outcomes but when interventions and outcomes requiring
      obstetric care were considered together, the magnitude of the increased risk was
      modest (adjusted RR 1.12, 95% CI 1.02-1.23, for BMI > 35 kg/m(2) relative to low
      risk women of normal weight). Nulliparous low risk women of normal weight had
      higher absolute risks and were more likely to require obstetric intervention or
      care than otherwise healthy multiparous women with BMI > 35 kg/m(2) (maternal
      composite outcome: 53% versus 21%). The perinatal composite outcome exhibited a
      similar pattern. CONCLUSIONS: Otherwise healthy multiparous obese women may have
      lower intrapartum risks than previously appreciated. BMI should be considered in
      conjunction with parity when assessing the potential risks associated with birth
      in non-obstetric unit settings.

PMID- 24034833
TI  - Intravoxel incoherent motion (IVIM) in evaluation of breast lesions: comparison
      with conventional DWI.
AB  - OBJECTIVES: To obtain perfusion as well as diffusion information in normal breast
      tissues and breast lesions from intravoxel incoherent motion (IVIM) imaging with
      biexponential analysis of multiple b-value diffusion-weighted imaging (DWI) and
      compare these parameters to apparent diffusion coefficient (ADC) obtained with
      monoexponential analysis in their ability to discriminate benign lesions and
      malignant tumors. MATERIALS AND METHODS: In this prospective study, informed
      consent was acquired from all patients. Eighty-four patients with 40 malignant
      tumors, 41 benign lesions, 30 simple cysts and 39 normal breast tissues were
      imaged at 1.5 T utilizing contrast-enhanced magnetic resonance imaging (MRI) and
      DWI using 12 b values (range: 0-1000 s/mm(2)). Tissue diffusivity (D), perfusion
      fraction (f) and pseudo-diffusion coefficient (D*) were calculated using
      segmented biexponential analysis. ADC (b = 0 and 1000 s/mm(2)) was calculated
      with monoexponential fitting of the DWI data. D, f, D* and ADC values were
      obtained for normal breast tissues, simple cysts, benign lesions and malignant
      tumors. Receiver operating characteristic analysis was performed for all DWI
      parameters. RESULTS: There was good interobserver agreement on the measurements
      between the 2 observers. D values were significantly different among malignant
      tumors, benign lesions, simple cysts and normal breast tissues (P = 0.000) and it
      was the same result for f, D* and ADC values. Further comparisons of these 4
      parameters between every single pair were as the following. D and ADC values of
      malignant tumors were significantly smaller than those of benign lesions, simple
      cysts and normal tissues (P = 0.000, respectively). The f value of malignant
      tumors was significantly higher than that of benign lesions, simple cysts and
      normal breast tissues (P = 0.001, P = 0.000, and P = 0.000). D and ADC values
      demonstrated higher sensitivity and specificity in differentiating benign lesions
      and malignant tumors, with area under the curve (AUC) of 0.952 and 0.945,
      respectively, while f and D* with the lower AUC of 0.723 and 0.630, respectively.
      Combining f and D values had a sensitivity up to 98.75%. CONCLUSION: DWI response
      curves in malignant tumors, benign lesions and normal fibroglandular tissues are
      found to be biexponential fit in comparison with the monoexponential fit for
      simple cysts. IVIM provides separate quantitative measurement of D for
      cellularity and f and D* for vascularity and is helpful for differentiation
      between benign and malignant breast lesions.

PMID- 24034834
TI  - MR-guided biopsy of the prostate: comparison of diagnostic specimen quality with
      18 G and 16 G biopsy needles.
AB  - PURPOSE: To evaluate specimen quality and diagnostic differences between magnetic
      resonance (MR) compatible 16 G and 18 G biopsy needles in MR-guided biopsy (MRGB)
      of the prostate. MATERIALS AND METHODS: Semiautomatic MR compatible biopsy
      needles with a diameter of 16 G (Group A) or 18 G (Group B) were used to perform
      MRGB in 88 patients with suspected prostate cancer. After embedding and staining,
      length and width of all specimens (140 cores in Group A, 143 in Group B) were
      measured. Fragmentation, squeezing artifacts, and overall evaluability were
      evaluated using a quality score from 0 (no tissue) to 3 (optimal tissue quality).
      Groups were statistically compared; p-values <0.05 were regarded as significant.
      RESULTS: Demographic data were not significantly different between Group A and B
      with a mean age of 63 +/- 7.3 and 67 +/- 5.7 years; and a mean prostate-specific
      antigen of 12.6 +/- 10.3 ng/ml and 13.8 +/- 11.6 ng/ml, respectively (p=0.70).
      Area of longitudinally sectioned histological specimens was significantly larger
      in Group A than in Group B with 9.38 mm(2) (8.74; 10.02) and 7.95 mm(2) (7.32;
      8.59), respectively (p=0.002). However, there were significantly more cores
      without prostate tissue with 18 cores (12.9%) versus 3 cores (2.1%) in Groups A
      and B, respectively (p=0.004). Fragmentation, squeezing artifacts, and overall
      evaluability were not statistically different between the two groups. The rate of
      prostate cancer in the cores was also not significantly different between Groups
      A and B (22.1% and 24.5%; p=0.77). CONCLUSION: 16 G biopsy needles do not provide
      a relevant diagnostic advantage over 18 G needles in MRGB. Therefore, use of 18 G
      needles is not discouraged and may even be preferred as it is not expected to
      result in a relevant degradation of specimen quality or compromise in prostate
      cancer detection rate.

PMID- 24034835
TI  - Dynamic contrast-enhanced MRI in patients with muscle-invasive transitional cell
      carcinoma of the bladder can distinguish between residual tumour and post
      chemotherapy effect.
AB  - INTRODUCTION: Treatment of muscle-invasive bladder cancer with chemotherapy
      results in haemorrhagic inflammation, mimicking residual tumour on conventional
      MR images and making interpretation difficult. The aim of this study was to use
      dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to estimate
      descriptive and tracer kinetic parameters post-neoadjuvant chemotherapy and to
      investigate whether parameters differed in areas of residual tumour and
      chemotherapy-induced haemorrhagic inflammation (treatment effect, Tr-Eff).
      METHODS AND MATERIALS: Twenty-one patients underwent DCE-MRI scans with 2.5s
      temporal resolution before and following neoadjuvant chemotherapy. Regions-of
      interest (ROIs) were defined in areas suspicious of residual tumour on T2
      weighted MRI scans. Data were analysed semi-quantitatively and with a two
      compartment exchange model to obtain parameters including relative signal
      intensity (rSI80s) and plasma perfusion (Fp) respectively. The bladder was
      subsequently examined histologically after cystectomy for evidence of residual
      tumour and/or Tr-Eff. Differences in parameters measured in areas of residual
      tumour and Tr-Eff were examined using Student's t-test. RESULTS: Twenty-four
      abnormal sites were defined after neoadjuvant chemotherapy. On pathology, 10 and
      14 areas were identified as residual tumour and Tr-Eff respectively. Median
      rSI80s and Fp were significantly higher in areas of residual tumour than Tr-Eff
      (rSI80s = 2.9 vs 1.7, p < 0.001; Fp = 20.7 vs 9.1 ml/100ml/min, p = 0.03). The
      sensitivity and specificity for differentiating residual tumour from Tr-Eff were
      70% and 100% (rSI80s), 60% and 86% (Fp), and 75% and 100% when combined.
      CONCLUSION: DCE-MRI parameters obtained post-treatment are capable of
      distinguishing between residual tumour and treatment effect in patients treated
      for bladder cancer with neoadjuvant chemotherapy.

PMID- 24034836
TI  - Diagnosis of early sacroiliitis in seronegative spondyloarthropathies by DWI and
      correlation of clinical and laboratory findings with ADC values.
AB  - PURPOSE: Sacroiliitis is one of the diagnostic criteria of seronegative SpA. The
      purpose of our study is to show the signal characteristics of the sacral and
      iliac surfaces by DWI which may contribute in early diagnosis of sacroiliitis and
      investigate the correlation between ADC values and clinical and laboratory
      parameters. MATERIALS AND METHODS: 62 patients with inflammatory low back pain,
      with a history or suspect of seronegative SpA are enrolled into the study. 40 age
      and sex-matched subjects without SpA constituted the control group. After
      obtaining routine T1 and T2 weighted sequences, echo planar imaging at b values
      of 0, 400 and 800 was performed. ADC values on both surfaces of the both
      sacroiliac joints were measured in all subjects. The CRP and sedimentation
      results and the presence of arthritis and enthesitis were also correlated with
      the ADC values. RESULTS: ADC values on both surfaces of the both sacroiliac
      joints were found 0.23 * 10(-3)mm(2)/sn in the control group. In the patient
      group, mean ADC value of 0.48 * 10(-3)mm(2)/sn was obtained (p<0.001), which was
      statistically significant, compatible with the increased diffusion due to
      medullary edema in early sacroiliitis. There was a slight correlation between CRP
      and ADC values; presumed to be showing the relation between the activity of the
      disease and the active inflammation on DWI. There was no correlation between
      arthritis and enthesitis and the ADC values (p>0.001). CONCLUSION: DWI, by
      measuring ADC values, adds significant information in the early diagnosis of
      sacroiliitis and may help to evaluate the efficiency of the treatment.

PMID- 24034837
TI  - The 2-oxoglutarate supply exerts significant control on the lysine synthesis flux
      in Saccharomyces cerevisiae.
AB  - To determine the extent to which the supply of the precursor 2-oxoglutarate (2
      OG) controls the synthesis of lysine in Saccharomyces cerevisiae growing
      exponentially in high glucose, top-down elasticity analysis was used. Three
      groups of reactions linked by 2-OG were defined. The 2-OG supply group comprised
      all metabolic steps leading to its formation, and the two 2-OG consumer groups
      comprised the enzymes and transporters involved in 2-OG transformation into
      lysine and glutamate and their further utilization for protein synthesis and
      storage. Various 2-OG steady-state concentrations that produced different fluxes
      to lysine and glutamate were attained using yeast mutants with increasing
      activities of Krebs cycle enzymes and decreased activities of Lys synthesis
      enzymes. The elasticity coefficients of the three enzyme groups were determined
      from the dependence of the amino acid fluxes on the 2-OG concentration. The
      respective degrees of control on the flux towards lysine (flux control
      coefficients) were determined from their elasticities, and were 1.1, 0.41 and 
      0.52 for the 2-OG producer group and the Lys and Glu branches, respectively.
      Thus, the predominant control exerted by the 2-OG supply on the rate of lysine
      synthesis suggests that over-expression of 2-OG producer enzymes may be a highly
      effective strategy to enhance Lys production.

PMID- 24034839
TI  - Response to a letter from A. Huisman and R. van Wijk (Ektacytometry and Genetic
      Testing in Hereditary Red Cell Membrane Disorders).

PMID- 24034840
TI  - About a submucosal tracheal tumor.
AB  - The authors report the case of 46-year-old man with recurrent hemoptysis.
      Bronchoscopy revealed a submucosal tumor protruding into the tracheal lumen.
      Transbronchial biopsy failed to obtain a conclusive diagnosis; only surgery
      allowed complete resection of the tumor and confirmed the diagnosis of tracheal
      mucoepidermoid carcinoma. We discuss the unusual submucosal presentation of this
      tumor, and the contribution of surgery for diagnosis and therapy. 

PMID- 24034838
TI  - Identification of glycogen synthase kinase 3alpha as a therapeutic target in
      melanoma.
AB  - Deregulated expression or activity of kinases can lead to melanomas, but often
      the particular kinase isoform causing the effect is not well established, making
      identification and validation of different isoforms regulating disease
      development especially important. To accomplish this objective, an siRNA screen
      was undertaken that which identified glycogen synthase kinase 3alpha (GSK3alpha)
      as an important melanoma growth regulator. Melanocytes and melanoma cell lines
      representing various stages of melanoma tumor progression expressed both
      GSK3alpha and GSK3beta, but analysis of tumors in patients with melanoma showed
      elevated expression of GSK3alpha in 72% of samples, which was not observed for
      GSK3beta. Furthermore, 80% of tumors in patients with melanoma expressed elevated
      levels of catalytically active phosphorylated GSK3alpha (pGSK3alphaY279), but not
      phosphorylated GSK3beta (pGSK3betaY216). siRNA-mediated reduction in GSK3alpha
      protein levels reduced melanoma cell survival and proliferation, sensitized cells
      to apoptosis-inducing agents and decreased xenografted tumor development by up to
      56%. Mechanistically, inhibiting GSK3alpha expression using siRNA or the
      pharmacological agent AR-A014418 arrested melanoma cells in the G0/G1 phase of
      the cell cycle and induced apoptotic death to retard tumorigenesis. Therefore,
      GSK3alpha is a key therapeutic target in melanoma. 

PMID- 24034841
TI  - IDOMAL: the malaria ontology revisited.
AB  - BACKGROUND: With about half a billion cases, of which nearly one million fatal
      ones, malaria constitutes one of the major infectious diseases worldwide. A
      recently revived effort to eliminate the disease also focuses on IT resources for
      its efficient control, which prominently includes the control of the mosquito
      vectors that transmit the Plasmodium pathogens. As part of this effort, IDOMAL
      has been developed and it is continually being updated. FINDINGS: In addition to
      the improvement of IDOMAL's structure and the correction of some inaccuracies,
      there were some major subdomain additions such as a section on natural products
      and remedies, and the import, from other, higher order ontologies, of several
      terms, which were merged with IDOMAL terms. Effort was put on rendering IDOMAL
      fully compatible as an extension of IDO, the Infectious Disease Ontology. The
      reason for the difficulties in fully reaching that target were the inherent
      differences between vector-borne diseases and "classical" infectious diseases,
      which make it necessary to specifically adjust the ontology's architecture in
      order to comprise vectors and their populations. CONCLUSIONS: In addition to a
      higher coverage of domain-specific terms and optimizing its usage by databases
      and decision-support systems, the new version of IDOMAL described here allows for
      more cross-talk between it and other ontologies, and in particular IDO. The
      malaria ontology is available for downloading at the OBO Foundry
      (http://www.obofoundry.org/cgi-bin/detail.cgi?id=malaria_ontology) and the NCBO
      BioPortal (http://bioportal.bioontology.org/ontologies/1311).

PMID- 24034842
TI  - [Relation of IL-17 polymorphisms and serum levels in patients with chronic HCV
      infection].
AB  - OBJECTIVE: To investigate the association of single nucleotide polymorphisms
      (SNPs) in the interleukin 17 (IL-17) gene and serum protein levels in patients
      with chronic hepatitis C virus (HCV) infection. METHODS: A total of 228 patients
      with chronic HCV infection and 81 healthy controls were enrolled in the study.
      The frequencies of IL-17 rs8193036 and rs2275913 polymorphisms were detected by
      the TaqMan SNP genotyping assay. Serum levels of IL-17 protein were detected by
      ELISA. Pairwise comparisons were made by the Chi-square test, and the
      significance of between-group differences was assessed by the Student's t-test
      with P less than 0.05. RESULTS: The patients with chronic HCV infection and the
      healthy controls showed similar frequencies of the rs8193036 C/T allele (x2 =
      1.428, P = 0.232) and the rs2275913 A/G allele (x2 = 0.106, P = 0.744). In
      addition, the two groups showed similar distribution of the rs8193036 CC (chronic
      HCV infection: 46.49% vs. healthy controls: 41.98%), CT (45.61% vs. 44.44%) and
      TT (7.89% vs. 13.58%) genotypes (x2 = 2.346, P = 0.309), and of the rs2275913 AA
      (16.23% vs. 13.58%), AG (48.25% vs. 50.62%) and GG (35.53% vs. 35.80%) genotypes
      (x2 = 0.340, P = 0.844). Subgroup analysis of chronic HCV infection patients
      stratified according to HCV genotypes 1 and 2 showed no differences in the
      distribution of rs8193036 and rs2275913 alleles (x2 = 1.127, P = 0.288; x2 =
      1.088, P = 0.297) and genotypes (x2 = 2.825, P = 0.246; x2 = 0.970, P = 0.616).
      However, the chronic HCV infection group did show significantly higher levels of
      serum IL-17 than the controls (97.67+/-39.68 vs. 71.60+/-19.78 pg/ml, t = 2.414,
      P = 0.033). CONCLUSION: Chronic HCV infection is associated with increased serum
      IL-17; however, the IL-17 polymorphisms rs8193036 and rs2275913 were not
      associated with chronic HCV infection susceptibility in this study's Chinese
      cohort.

PMID- 24034843
TI  - [The difference of IL-28B polymorphisms between hepatitis C patients with and
      without cryoglobulinemia].
AB  - OBJECTIVE: To determine whether patients infected with chronic hepatitis C (CHC)
      show a differential distribution profile of IL-28B polymorphisms according to the
      presence of concomitant cryoglobulinemia. METHODS: Sixty-two consecutive CHC
      patients were enrolled in the study between December 2008 and December 2010. All
      patients received combination therapy of pegylated interferon alpha-2a (weekly,
      180 g, subcutaneous injection) plus ribavirin (daily, 10to15 mg/kg body weight,
      oral) for 48 weeks, with individualized dosage adjustments according to the
      patient's clinical situation. Cryoglobulins were detected visibly by separation
      of cryoprecipitates in patient serum samples. Three IL-28B SNPs (rs8099917,
      rs12979860, and rs12980275) were detected by sequencing. Response to treatment
      was assessed by measuring serum levels of HCV RNA by quantitative PCR at baseline
      (prior to treatment initiation), during treatment (4 and 12 weeks after treatment
      initiation), end of therapy (48 weeks after treatment initiation), and post
      treatment (24 weeks after end of therapy). The significance of between-group
      differences were assessed by the Chi-square and Fisher's exact tests. RESULTS:
      Cryoglobulinemia was detected in 43.5% (27/62) of the CHC patients and showed a
      female bias (59.3% vs. males: 34.3%, P = 0.05). Compared to CHC patients without
      cryoglobulinemia, the CHC patients with cryoglobulinemia showed significantly
      higher levels of HCV RNA at baseline (5.64+/-1.20 vs. 6.37+/-0.67, P less than
      0.05) but lower frequencies of the IL28B rs8099917 TT genotype (94.3% vs. 63.0%,
      P = 0.002), rs8099917 T allele (97.1% vs. 81.5%, P = 0.003), and rs12979860 C
      allele (94.3% vs. 83.3%, P = 0.048). CHC patients with cryoglobulinemia and
      having the rs8099917 TT, rs12979860 CC, or rs12980275 AA genotype achieved a
      higher rate of sustained virological response. CONCLUSION: Cryoglobulinemia in
      CHC patients is associated with a differential distribution of IL-28B
      polymorphisms, and certain polymorphisms may be related to anti-viral treatment
      response.

PMID- 24034844
TI  - [Relation between serum levels of high mobility group box 1 and hepatitis B virus
      related acute-on-chronic liver failure].
AB  - OBJECTIVE: To evaluate the levels of high mobility group box 1 protein (HMGB1) in
      serum of patients with hepatitis B virus (HBV)-related acute-on-chronic liver
      failure (ACLF) and investigate its potential relation to the clinical features of
      these patients. METHODS: Sixty patients with HBV-related ACLF, 30 patients with
      chronic hepatitis B (CHB), and 24 healthy individuals (controls) were enrolled in
      the study. Markers of liver function, such as aspartate aminotransferase (AST),
      were measured by routine biochemical methods. Imaging studies, such as abdominal
      computed tomography or magnetic resonance imaging, were used for disease staging.
      Serum levels of HMGB1 were measured by ELISA. Deaths within the 2-month follow-up
      after serum collection were used for the survival analysis. Patients who
      developed peritonitis, pneumonia, or other bacterial and fungal infections during
      the 2-month follow-up after serum collection were classified as the infected
      group. Pairwise comparisons were carried out by t-test, and multiple comparisons
      were carried out by analysis of variance. RESULTS: Patients with HBV-related ACLF
      had significantly higher serum levels of HMGB1 than CHB patients or controls (P =
      0.003). Among the patients with HBV-related ACLF, those in the late stage (n =
      20) had significantly higher levels of HMGB1 than those in the early stage (n =
      20) (P = 0.005). The serum levels of HMGB1 correlated well with AST level in
      patients with HBV-related ACLF (P = 0.006). In addition, patients with HBV
      related ACLF who developed infection or died during follow-up also had
      significantly higher levels of HMGB1 (P = 0.028 or P = 0.017, respectively).
      CONCLUSION: Enhanced serum level of HMGB1 is associated with development of HBV
      related ACLF in CHB patients. The strong correlation between HMGB1 and AST levels
      suggest that HMGB1 may be useful as a prognostic marker for development of ACLF.

PMID- 24034845
TI  - [Effect of antiviral therapy on the prognosis of patients with chronic hepatitis
      B-related cirrhosis].
AB  - OBJECTIVE: To conduct a meta-analysis to study the effect of antiviral therapy on
      the prognosis of patients with chronic hepatitis B (CHB)-related cirrhosis.
      METHODS: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials,
      Chinese Biomedical Database, Chinese Journals Full-text Database, and Wan Fang
      Digital Journal Full-text Database were searched for studies on nucleoside
      analogues antiviral treatment outcome of patients with CHB-related cirrhosis (vs.
      controls without antiviral therapy) published between January 1998 and March
      2012. Data extraction and quality assessment was performed by two independent
      investigators. Heterogeneity was assessed by the I2 index. In the case of
      homogeneity the random-effects model was applied, and in the case of
      heterogeneity the fixed-effects model was applied. The odds ratios (ORs) with 95%
      confidence intervals (CIs) were calculated. RESULTS: Seven studies were included
      in the meta-analysis: one high-quality randomized-controlled trial (RCT) study,
      four prospective cohort studies, and two case-control studies. Compared to the
      control group, the group treated with antiviral therapy showed a significantly
      lower incidence of hepatocellular carcinoma (11.2%, 76/680 vs. 6.7%, 75/1116; OR
      = 0.56, 95% CI: 0.40 to 0.79, P = 0.001) and lower mortality (23.6%, 78/331 vs.
      10.8%, 43/398; OR = 0.36, 95% CI: 0.23 to 0.55, P = 0.000). CONCLUSION: Antiviral
      therapy with nucleoside analogues significantly reduces the incidence of
      hepatocellular carcinoma and mortality in patients with CHB-related cirrhosis.

PMID- 24034846
TI  - [Interleukin-32 expression is induced by hepatitis B virus].
AB  - OBJECTIVE: To investigate whether hepatitis B virus (HBV) can induce the
      expression of the host-encoded cytokine interleukin-32 (IL-32) and its effects on
      host signaling mechanisms related to HBV pathogenesis. METHODS: A eukaryotic
      expression vector harboring an enhanced green fluorescent protein was constructed
      with HBV genomic sequences (pIRES2-HBV-EGFP) and transfected into HepG2 cells. In
      addition, the nuclear factor-kappa B (NF-kB) subunits, p50 and p65, were
      transfected respectively into HepG2 cells. In both cases, 48 hrs after
      transfection, IL-32 expression was determined at the mRNA and protein levels
      using real-time PCR and ELISA and western blot, respectively. The HepG2 cells
      transfected with pIRES2-HBV-EGFP were also treated with the NF-kB inhibitor SN50
      at various concentrations, and the effects on IL-32 protein expression 48 hrs
      later were evaluated by western blot. Significance of between-group differences
      was assessed by the Student's t-test. RESULTS: Transfection with pIRES2-HBV-EGFP
      led to significantly higher IL-23 expression than transfection with empty vector
      (mRNA: 2.8-fold higher and protein: 4.5-fold higher; both P less than 0.05).
      Transfection of p50 and p65 proteins led to significantly higher IL-32 expression
      (both P less than 0.05), and NF-kB activation was found to be required for HBV
      induced IL-32 expression. CONCLUSION: IL-32 expression is induced by HBV in HepG2
      cells. This host-encoded cytokine, and its downstream activation of NF-kB, may be
      involved in the pathogenesis of HBV, especially in the subsequent liver
      inflammation that accompanies HBV infection.

PMID- 24034847
TI  - [Roles of full-length and truncated hepatitis B virus X protein and of
      interactions with the host-encoded damaged DNA binding protein 1 in HBV
      replication].
AB  - OBJECTIVE: To investigate the roles of the hepatitis B virus (HBV)-encoded X
      protein (HBx), including the full-length and truncated isoforms, and in
      conjunction with the host-encoded damaged DNA binding protein 1 (DDB1) in HBV
      replication. METHODS: Recominant expression plasmids carrying the wild-type HBV
      genome (pGEM-HBV1.2) or with deletion of the full-length HBx protein (pHBV
      deltaX), or carrying the full-length HBx protein (pSI-X) or the HBx1to101 (pSI
      X1to101) or HBx43to154 (pSI-X43to154) isoforms were constructed for transfection
      into HepG2 cells. The pcDNA6.2-GW/EmGFP-miR (DDB1-miRNA) vector was constructed
      for silencing of the DDB1 gene in co-transfected HepG2 cells. At 72 h after
      transfections, DDB1 silencing was confirmed by western blot analysis and real
      time quantitive reverse transcription PCR, HBV DNA copies number was assessed by
      real time PCR, and levels of hepatitis B surface antigen (HbsAg) and hepatitis B
      e antigen (HbeAg) were determined by ELISA. Differences between groups was
      statistically analyzed by single-factor analysis of variance and the t-test.
      RESULTS: Transfection with pHBV-deltaX led to reductions in DDB1 mRNA (to 52.74%
      of that in the wild-type pGEM-HBV1.2 transfected cells), HBV replication (to
      55.49%), HBsAg level (48.05%), and HBeAg level (46.22%). Co-transfection with pSI
      X or pSI-X43to154, but not with pSI-X1to101, restored the pHBV-deltaX-induced
      reductions in DDB1 mRNA, HBV replication, HBsAg and HBeAg to wild-type levels.
      The quantity of DDB1 mRNA was approximately parallel with the quantity of HBV DNA
      copies in all the HepG2 transfection groups. CONCLUSION: The COOH-terminal amino
      acids of HBx are required for HBV replication in hepatocytes, possibly involving
      the host-encoded DDB1 protein.

PMID- 24034848
TI  - [Short hairpin RNA mediated glypican-3 silencing inhibits hepatoma cell
      invasiveness and disrupts molecular pathways of angiogenesis].
AB  - OBJECTIVE: To construct glypican-3 (GPC-3) short hairpin RNA (shRNA) and
      investigate the effects of GPC-3 transcription silencing on hepatoma cell
      invasion and angiogenesis mechanisms. METHODS: GPC-3-specific shRNA and non
      target control shRNA were constructed and transfected into the human hepatoma
      cell lines HepG2, MHCC-97H, and Huh7. shRNA-mediated silencing of GPC-3
      expression was confirmed at the mRNA and protein levels by fluorescence
      quantitative reverse transcription (FQRT)-PCR and western blotting, respectively.
      The effect of silenced GPC-3 expression on cell proliferation was detected by EdU
      and sulforhodamine B assays, on migration by wound healing (scratch) assay, on
      invasion by transwell chamber assay, and on apoptosis by luminescence assay of
      caspase-3/7 activity. The effect of silenced GPC-3 expression on angiogenesis
      related signaling factors was detected by FQRT-PCR (for the glioma-associated
      oncogene homolog-1 hedgehog signaling factor, GLI1, and the beta-catenin Wnt
      signaling factor, b-catenin), immunofluorescent staining (for the insulin-like
      growth factor-II, IGF-II), and ELISA (for the vascular endothelial growth factor,
      VEGF). Pairwise comparisons were made by the independent sample t-test, and
      multiple comparisons were made by one-way ANOVA. RESULTS: In all cell lines,
      transfection with the GPC-3-specific shRNA significantly reduced GPC-3 mRNA
      levels (% reduction as compared to the non-target control shRNA: HepG2, 89.2+/
      6.0%, t = -25.753, P less than 0.001; MHCC-97H, 75.3+/-4.9%, t = -26.487, P less
      than 0.001; Huh7, 73.6+/-4.6%, t = -27.607, P less than 0.001); the GPC-3 protein
      levels were similarly reduced. The GPC-3 shRNA-silenced cells showed
      significantly reduced proliferative, migratory and invasive capacities, as well
      as significantly increased apoptosis. The shRNA-mediated GPC-3 silencing was
      accompanied by significant down-regulation of b-catenin mRNA (HepG2, 46.9+/-0.6%;
      MHCC-97H, 67.5+/-2.7%; Huh7, 56.3+/-8.4%) and significant up-regulation of GLI1
      mRNA (HepG2, 49.2+/-28.6%; MHCC-97H, 54.6+/-24.4%; Huh7, 31.6+/-15.7%). At 72 h
      after transfection, the HepG2 cells showed significant down-regulation of VEGF
      protein (54.3+/-1.5%, t = 46.746, P less than 0.001). CONCLUSION: GPC-3
      contributes to migration, invasion, angiogenesis, and apoptosis of hepatoma
      cells, possibly through its interactions with the Wnt/b-catenin and Hedgehog
      signaling pathways. GPC-3 may represent a useful target for gene silencing by
      molecular-based therapies to treat hepatocellular carcinoma.

PMID- 24034849
TI  - [Gene therapy using a dominant negative form of the protein phosphatase 2A
      catalytic subunit a driven by a hepatoma tissue-specific promoter achieves
      effective growth inhibition of hepatoma cells].
AB  - OBJECTIVE: To generate a gene delivery plasmid carrying the dominant negative
      form of the protein phosphatase 2A catalytic subunit a (DN-PP2Aca) driven by a
      hepatocellular carcinoma (HCC) tissue-specific promoter and investigate its
      ability to inhibit growth of cultured hepatoma cells. METHODS: The gene delivery
      plasmid was constructed by PCR-amplifying DN-PP2Aca from wild-type PP2Aca using
      site-directed mutagenesis and then ligating the sequence-verified amplicon
      downstream of an alpha-fetoprotein enhancer and phosphoglycerate kinase promoter
      (AFpg) in the luciferase reporter vector pGL3-Basic. Following transfection into
      two AFP+ hepatoma cell lines (HepG2 and HepG3) and two AFP- hepatoma cell lines
      (SK-HEP-1 and L02), the transcriptional activity of the AFpg-driven DN-PP2Aca
      plasmid was tested using luciferase reporter gene assay and western blotting. The
      effect on cell growth was tested using MTT assay. Between group differences were
      assessed by t-test. RESULTS: The AFpg-driven DN-PP2Aca plasmid showed high
      transcriptional activity and protein expression in both HepG2 and Hep3B cells. At
      72 h after transfection, the proliferation capacities were repressed by 42.65%+/
      3.99% (P = 0.0002) and 39.87%+/-3.91% (P = 0.0002) in AFP+ HepG2 and Hep3B cells,
      respectively (vs. untransfected). In contrast, the plasmid was transcriptionally
      inactive in and had no effect on proliferation of AFP- cells. CONCLUSION: The
      AFpg-driven DN-PP2Aca plasmid exhibits selective cytotoxicity against AFP+
      hepatoma cells, and may represent a useful gene therapy strategy to treat HCC.

PMID- 24034850
TI  - [Orthogonal design based optimization of a mouse model of acute liver failure
      induced by D-galactosamine and lipopolysaccharide].
AB  - OBJECTIVE: To apply an orthogonal design optimization strategy to a mouse model
      of acute liver failure induced by D-galactosamine (D-GalN) and lipopolysaccharide
      (LPS) exposure. METHODS: A four-level orthogonal array design (L16(45)) was
      constructed to test factors with potential impact on successful establishment of
      the model (D-GalN and LPS dosages, and dilution rate of the D-GalN/LPS mixture).
      The mortality rate of mice within 24 hours of D-GalN/LPS administration was
      determined by the Kaplan-Meier method. The model outcome was verified by changes
      in serum alanine transferase level, liver histology, and hepatocyte apoptosis.
      RESULTS: The orthogonal array identified the optimal model technique as
      intraperitoneal injection of a combination of D-GalN and LPS at dosages of 350
      mg/kg and 30 mug/kg, respectively, and using a dilution rate of 3. The dosages
      tested had no effect on survival. The typical signs of liver failure appeared at
      6 hrs after administration of the D-GalN/LPS combination. CONCLUSION: The
      orthogonal design optimization strategy provided a procedure for establishing a
      mouse model of acute liver failure induced by D-GalN and LPS that showed
      appropriate disease outcome and survival, and which will serve to improve future
      experimental research of acute liver failure.

PMID- 24034851
TI  - [Hyperammonemia-induced hepatic injury in rats: characterization of a new animal
      model].
AB  - OBJECTIVE: To establish an accurate new rat model of hyperammonemia-induced liver
      injury for use in studies of the molecular mechanisms underlying acute liver
      failure (ALF). METHODS: Twenty-six Sprague-Dawley rats were administered D
      galactosamine (400 mg/kg) and endotoxin (50 mug/kg) via intraperitoneal injection
      to induce ALF and sacrificed at 12 h post-injection (ALF-12 group, n = 10) or 24
      h post-injection (ALF-24 group, n = 16). Ten rats administered physiological
      saline served as the control group. In addition, 20 rats were given serial oral
      administrations of 10% NH4Cl solution (10 ml/kg, every 8 hrs) to establish the
      hyperammonemia-induced liver injury model; an additional 20 rats were prepared in
      parallel to serve as the ALF control group (n = 10; D-galactosamine at 800 mg/kg
      every 6 d for 30 days) and the physiological saline control group (n = 10). Serum
      samples were collected from each mouse and used to detect markers of liver
      function, including alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), alpha-fetal protein (AFP), and gamma-glutamyltransferase (GGT), as well as
      blood ammonia (BA) level and prothrombin time activity (PT-A). Affects on liver
      histology was assessed by hematoxylin and eosin staining of resected liver
      tissues, and on apoptosis by TUNEL assay and calculating the apoptotic index
      (AI). RESULTS: ALF rats showed elevated levels of ALT (1202.51+/-282.00 U/L), AST
      (1560.14+/-298.98 U/L), and BA (165.9+/-23.6 mumol/L) as early as 6 hrs after
      model establishment; these levels peaked at 12 hrs after model establishment
      (ALT: 774.40+/-207.65 U/L; AST: 967.60+/-121.94 U/L; BA: 143.4+/-18.1 mumol/L; P
      less than 0.05). No significant variations were detected in the levels of AFP
      (except for the ALF-24 group) or GGT. Liver tissues of the ALF-12 and ALF-24
      groups showed large or diffuse hemorrhagic necroses with sinusoidal congestion or
      spotty bleeding, as well as increased AI. Hyperammonemia-induced liver injury
      rats showed elevated levels of ALT and BA as early as 6 hrs after model
      establishment. Similar to the ALF rats, AFP and GGT were unaffected and AI
      increased. However, in contrast to the ALF rats, the liver tissues of the
      hyperammonemia-induced liver injury rats showed no signs of hepatocyte swelling,
      necrosis, or inflammatory cell invasion. CONCLUSION: ALF rats and hyperammonemia
      induced liver injury rats have elevated BA and marked hepatocyte necrosis. Given
      that reducing the level of ammonemia can improve the animal's biochemistry
      indexes, it is likely that hyperammonemia plays a role in acute liver injury or
      ALF consequent to repeated injury. The pathogenic mechanisms of repeated injury
      may involve promotion of hepatocyte apoptosis in conjunction with inhibition of
      cellular regeneration.

PMID- 24034852
TI  - Domain exchange at the 3' end of the gene encoding the fratricide meningococcal
      two-partner secretion protein A.
AB  - BACKGROUND: Two-partner secretion systems in Gram-negative bacteria consist of an
      outer membrane protein TpsB that mediates the secretion of a cognate TpsA protein
      into the extracellular milieu. TpsA proteins have diverse, often virulence
      related functions, and some of them inhibit the growth of related bacteria. In
      Neisseria meningitidis, several functions have been attributed to the TpsA
      proteins. Downstream of the tpsB and tpsA genes, several shorter tpsA-related
      gene cassettes, called tpsC, are located interspersed with intervening open
      reading frames (IORFs). It has been suggested that the tpsC cassettes may
      recombine with the tpsA gene as a mechanism of antigenic variation. Here, we
      investigated (i) whether TpsA of N. meningitidis also has growth-inhibitory
      properties, (ii) whether tpsC cassettes recombine with the tpsA gene, and (iii)
      what the consequences of such recombination events might be. RESULTS: We
      demonstrate that meningococcal TpsA has growth-inhibitory properties and that the
      IORF located immediately downstream of tpsA confers immunity to the producing
      strain. Although bioinformatics analysis suggests that recombination between tpsC
      cassettes and tpsA occurs, detailed analysis of the tpsA gene in a large
      collection of disease isolates of three clonal complexes revealed that the
      frequency is very low and cannot be a mechanism of antigenic variation. However,
      recombination affected growth inhibition. In vitro experiments revealed that
      recombination can be mediated through acquirement of tpsC cassettes from the
      environment and it identified the regions involved in the recombination.
      CONCLUSIONS: Meningococcal TpsA has growth-inhibitory properties. Recombination
      between tpsA and tpsC cassettes occurs in vivo but is rare and has consequences
      for growth inhibition. A recombination model is proposed and we propose that the
      main goal of recombination is the collection of new IORFs for protection against
      a variety of TpsA proteins.

PMID- 24034854
TI  - Low-dose mirtazapine in treatment of major depression developed following severe
      nausea and vomiting during pregnancy: two cases.
AB  - This report presents the successful use of low-dose mirtazapine in the treatment
      of major depression that developed following severe nausea and vomiting symptoms
      during the early gestational weeks in two cases. The psychiatric diagnosis was
      determined with the Structured Clinical Interview for the Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition. Assessments were
      performed with the Clinical Global Impression-Improvement Scale and the 17-item
      Hamilton Rating Scale for Depression. Further large-scale studies should be
      carried out to confirm the useful effects observed in these cases.

PMID- 24034853
TI  - Muslim communities learning about second-hand smoke (MCLASS): study protocol for
      a pilot cluster randomised controlled trial.
AB  - BACKGROUND: In the UK, 40% of Bangladeshi and 29% of Pakistani men smoke
      cigarettes regularly compared to the national average of 24%. As a consequence,
      second-hand smoking is also widespread in their households which is a serious
      health hazard to non-smokers, especially children. Smoking restrictions in
      households can help reduce exposure to second-hand smoking. This is a pilot trial
      of 'Smoke Free Homes', an educational programme which has been adapted for use by
      Muslim faith leaders, in an attempt to find an innovative solution to encourage
      Pakistani- and Bangladeshi-origin communities to implement smoking restrictions
      in their homes. The primary objectives for this pilot trial are to establish the
      feasibility of conducting such an evaluation and provide information to inform
      the design of a future definitive study. METHODS/DESIGN: This is a pilot cluster
      randomised controlled trial of 'Smoke Free Homes', with an embedded preliminary
      health economic evaluation and a qualitative analysis. The trial will be carried
      out in around 14 Islamic religious settings. Equal randomisation will be employed
      to allocate each cluster to a trial arm. The intervention group will be offered
      the Smoke Free Homes package (Smoke Free Homes: a resource for Muslim religious
      teachers), trained in its use, and will subsequently implement the package in
      their religious settings. The remaining clusters will not be offered the package
      until the completion of the study and will form the control group. At each
      cluster, we aim to recruit around 50 households with at least one adult resident
      who smokes tobacco and at least one child or a non-smoking adult. Households will
      complete a household survey and a non-smoking individual will provide a saliva
      sample which will be tested for cotinine. All participant outcomes will be
      measured before and after the intervention period in both arms of the trial. In
      addition, a purposive sample of participants and religious leaders/teachers will
      take part in interviews and focus groups. DISCUSSION: The results of this pilot
      study will inform the protocol for a definitive trial. TRIAL REGISTRATION:
      Current Controlled Trials ISRCTN03035510.

PMID- 24034855
TI  - Applications of Floquet-Magnus expansion, average Hamiltonian theory and Fer
      expansion to study interactions in solid state NMR when irradiated with the magic
      echo sequence.
AB  - This work presents the possibility of applying the Floquet-Magnus expansion and
      the Fer expansion approaches to the most useful interactions known in solid-state
      nuclear magnetic resonance using the magic-echo scheme. The results of the
      effective Hamiltonians of these theories and average Hamiltonian theory are
      presented. 

PMID- 24034856
TI  - Modulation of ligand-heme reactivity by binding pocket residues demonstrated in
      cytochrome c' over the femtosecond-second temporal range.
AB  - The ability of hemoproteins to discriminate between diatomic molecules, and the
      subsequent affinity for their chosen ligand, is fundamental to the existence of
      life. These processes are often controlled by precise structural arrangements in
      proteins, with heme pocket residues driving reactivity and specificity. One such
      protein is cytochrome c', which has the ability to bind nitric oxide (NO) and
      carbon monoxide (CO) on opposite faces of the heme, a property that is shared
      with soluble guanylate cycle. Like soluble guanylate cyclase, cytochrome c' also
      excludes O2 completely from the binding pocket. Previous studies have shown that
      the NO binding mechanism is regulated by a proximal arginine residue (R124) and a
      distal leucine residue (L16). Here, we have investigated the roles of these
      residues in maintaining the affinity for NO in the heme binding environment by
      using various time-resolved spectroscopy techniques that span the entire
      femtosecond-second temporal range in the UV-vis spectrum, and the femtosecond
      nanosecond range by IR spectroscopy. Our findings indicate that the tightly
      regulated NO rebinding events following excitation in wild-type cytochrome c' are
      affected in the R124A variant. In the R124A variant, vibrational and electronic
      changes extend continuously across all time scales (from fs-s), in contrast to
      wild-type cytochrome c' and the L16A variant. Based on these findings, we propose
      a NO (re)binding mechanism for the R124A variant of cytochrome c' that is
      distinct from that in wild-type cytochrome c'. In the wider context, these
      findings emphasize the importance of heme pocket architecture in maintaining the
      reactivity of hemoproteins towards their chosen ligand, and demonstrate the power
      of spectroscopic probes spanning a wide temporal range.

PMID- 24034857
TI  - Clonal growth of human melanocytes using cell-free extracellular matrix.

PMID- 24034858
TI  - Atypical teratoid/rhabdoid tumor with ganglioglioma-like differentiation: case
      report and review of the literature.
AB  - Atypical teratoid/rhabdoid tumor (AT/RT) is a highly aggressive embryonal tumor
      of the central nervous system, which typically affects young children. A
      characteristic feature of AT/RT is a polyphenotypic immunoprofile and
      ultrastructural diversity. The morphologic and antigenic heterogeneity of AT/RT
      give it the potential to mimic other embryonal central nervous system tumors,
      epithelial neoplasms or mesenchymal tumors. Alternatively, "collision-type"
      tumors have been published, in which AT/RT coexists with a separate low-grade
      central nervous system tumor. Here, we report a case of AT/RT with morphologic
      and immunohistochemical evidence of extensive ganglioglioma-like differentiation
      with only a small focal primitive component and minimal rhabdoid cytology.
      Fluorescence in situ hybridization and immunohistochemistry demonstrated
      INI1/BAF47 gene/protein losses in both histologic components. To the best of our
      knowledge, this is the first reported case of AT/RT with extensive ganglioglioma
      like differentiation. This unique case supports the notion that routine
      application of INI1 stains/in situ hybridization can capture AT/RT with
      unexpected patterns of differentiation. 

PMID- 24034859
TI  - Lynch syndrome-associated colorectal carcinoma: frequent involvement of the left
      colon and rectum and late-onset presentation supports a universal screening
      approach.
AB  - The optimal strategy for screening patients with colorectal carcinoma for Lynch
      syndrome (LS) is a subject of continued debate in the literature with some
      advocating universal screening while others arguing for selective screening. We
      evaluated 1292 colorectal carcinomas for DNA mismatch repair protein
      abnormalities and identified 150 (11.6%) tumors demonstrating high-levels of
      microsatellite instability (MSI-H). MSI-H colorectal carcinomas were divided into
      sporadic (112/1292, 8.7%) and LS/probable LS-associated (38/1292, 2.9%) groups
      based on BRAF V600E mutation, MLH1 promoter hypermethylation, cancer history, and
      germline mismatch repair gene mutation. All MSI-H colorectal carcinomas were
      analyzed for grade, location, and tumor histology. The utility of the revised
      Bethesda guidelines and published predictive pathology models for MSI-H
      colorectal carcinomas (PREDICT and MSPath) were evaluated. Left-sided MSI-H
      colorectal carcinomas were more frequently associated with LS compared with right
      sided MSI-H colorectal carcinomas (12/21, 57% versus 26/129, 20%, P = .0008).
      There was no significant difference in histology between sporadic MSI-H and
      LS/probable LS-associated colorectal carcinomas except for a slightly higher
      proportion of sporadic MSI-H tumors demonstrating tumor-infiltrating lymphocytes
      (81% versus 61%, P = .015). Neither pathology predictive model identified all LS
      associated colorectal carcinomas (PREDICT: 33/38, 87%; MSPath: 35/38, 92%).
      12/117 (10%) MSI-H colorectal carcinomas identified in patients >60 years were
      LS/probable LS-associated. Our results demonstrate that models of predicting MSI
      H fail to identify LS-associated colorectal carcinoma given their reliance on
      right-sided location. A significant proportion (32%) of LS-associated colorectal
      carcinoma is identified in patients >60 years. Finally, our results demonstrate
      similar morphologic features between LS-associated and sporadic MSI-H colorectal
      carcinomas. 

PMID- 24034860
TI  - Consensus on ventral rectopexy: report of a panel of experts.

PMID- 24034861
TI  - To stent or not to stent: the President Bush stent controversy.

PMID- 24034862
TI  - Safety and feasibility of performing staged non-culprit vessel percutaneous
      coronary intervention within the index hospitalization in patients with ST
      segment elevation myocardial infarction and multivessel disease.
AB  - OBJECTIVES: To determine whether staged percutaneous coronary intervention (PCI)
      within the same hospitalization as primary PCI is safe. BACKGROUND: In ST-segment
      elevation myocardial infarction (STEMI) patients with multivessel disease
      undergoing primary PCI, staged non-culprit vessel PCI at a separate session is
      recommended. METHODS: We conducted a retrospective analysis of 282 consecutive
      STEMI patients with multivessel disease who underwent primary PCI followed by
      staged PCI of the non-culprit vessel. Patients were categorized into staged PCI
      in the same hospitalization (n=184) and staged PCI at a separate hospitalization
      within 8 weeks of primary PCI (n=98). RESULTS: Baseline characteristics,
      presentation of STEMI, and procedural characteristics were similar in both
      groups. Contrast amount was higher in the separate hospitalization group for both
      index (175 vs. 153 ml, p=0.011) and staged (144 vs. 120 ml, p=0.004) procedures.
      More staged left main PCI was performed in the separate hospitalization group
      (3.9 vs. 0.3%, p=0.008). Angiographic success of staged PCI was similar in both
      groups, with similar rates of vascular complications and major bleeding.
      Following staged PCI, in-hospital major adverse cardiac events (3.3 vs. 1.0%,
      p=0.43) and mortality (2.7 vs. 0%, p=0.17) were similar in both groups.
      CONCLUSIONS: Our study supports the safety and feasibility of staged PCI within
      the same hospitalization as primary PCI, achieving similar procedural success and
      in-hospital outcomes as staged PCI at a separate hospitalization. Higher contrast
      amount used during primary PCI and presence of left main lesion in non-culprit
      vessels may influence the decision to stage the PCI at a separate
      hospitalization.

PMID- 24034863
TI  - Successful catheter aspiration and local low-dose thrombolysis in an acute renal
      artery embolism.
AB  - Acute renal artery embolism (RAE) is a clinical rare condition and diagnosis of
      it is often delayed or missed due to both the rarity of the disease and its non
      specific clinical presentation. The exact role and optimal timing of endovascular
      revascularization remain controversial and uncertain. This article discusses a
      case of acute renal artery embolism caused by atrial fibrillation. Endovascular
      renal thrombus aspiration combined with local low-dose thrombolysis reversed the
      renal ischemia with restoration of renal function despite prolonged ischemia. 

PMID- 24034864
TI  - Reduction in dental plaque in patients with mental disorders through the dental
      hygiene care programme.
AB  - OBJECTIVE: To develop a dental hygiene care programme based on the specific needs
      of patients with mental disorders and to suggest practical guidelines to improve
      the oral health care of these patients. METHODS: A total of 73 patients with
      mental illness participated in the study. The patients were randomly classified
      into three groups and followed over 12 weeks at 4-week intervals. A newly
      designed dental hygiene care programme using flash-based video, brochures and a
      toothpick method was implemented by five dental hygienists. Plaque index,
      stimulated saliva, subjective oral dryness and dental caries activity were
      analysed as outcome variables. RESULTS: Results showed that the dental plaque
      index significantly decreased after each session (P < 0.0001) in all three
      groups, and significant differences were found between groups (P = 0.036).
      Patients' oral dryness decreased significantly, but stimulated saliva and dental
      caries activity did not improve. CONCLUSION: The results of this study suggest
      that the dental hygiene care programme, which made use of a short, 10-min flash
      based video and brochures every 4 weeks, was effective in reducing the dental
      plaque index of patients with mental disorders.

PMID- 24034865
TI  - Genome wide sequence analysis grants unbiased definition of species boundaries in
      "Candidatus Phytoplasma".
AB  - The phytoplasmas are currently named using the Candidatus category, as the
      inability to grow them in vitro prevented (i) the performance of tests, such as
      DNA-DNA hybridization, that are regarded as necessary to establish species
      boundaries, and (ii) the deposition of type strains in culture collections. The
      recent accession to complete or nearly complete genome sequence information
      disclosed the opportunity to apply to the uncultivable phytoplasmas the same
      taxonomic approaches used for other bacteria. In this work, the genomes of 14
      strains, belonging to the 16SrI, 16SrIII, 16SrV and 16SrX groups, including the
      species "Ca. P. asteris", "Ca. P. mali", "Ca. P. pyri", "Ca. P. pruni", and "Ca.
      P. australiense" were analyzed along with Acholeplasma laidlawi, to determine
      their taxonomic relatedness. Average nucleotide index (ANIm), tetranucleotide
      signature frequency correlation index (Tetra), and multilocus sequence analysis
      of 107 shared genes using both phylogenetic inference of concatenated (DNA and
      amino acid) sequences and consensus networks, were carried out. The results were
      in large agreement with the previously established 16S rDNA based classification
      schemes. Moreover, the taxonomic relationships within the 16SrI, 16SrIII and
      16SrX groups, that represent clusters of strains whose relatedness could not be
      determined by 16SrDNA analysis, could be comparatively evaluated with non
      subjective criteria. "Ca. P. mali" and "Ca. P. pyri" were found to meet the
      genome characteristics for the retention into two different, yet strictly related
      species; representatives of subgroups 16SrI-A and 16SrI-B were also found to meet
      the standards used in other bacteria to distinguish separate species; the genomes
      of the strains belonging to 16SrIII were found more closely related, suggesting
      that their subdivision into Candidatus species should be approached with caution.

PMID- 24034866
TI  - MR-guided focused ultrasound for the novel and innovative management of
      osteoarthritic knee pain.
AB  - BACKGROUND: Severe knee pain associated with osteoarthritis (OA) is one of the
      most common and troublesome symptoms in the elderly. Recently, local bone
      denervation by MR-guided focused ultrasound (MRgFUS) has been demonstrated as a
      promising tool for pain palliation of bone metastases. The purpose of this study
      was to develop a novel treatment for knee OA using MRgFUS, and to validate its
      safety and efficacy. METHODS: Eight patients with medial knee pain and eligible
      for total knee arthroplasty were included. MR-guided focused sonication
      treatments were applied to bone surface just below the rim osteophyte of medial
      tibia plateau with real-time monitoring of the temperature in the target sites.
      The pain intensity during walking was assessed on a 100 mm visual analog scale
      (VAS) before and after treatment. Pressure pain thresholds (PPTs) were also
      evaluated over several test sites adjacent to the sonication area and control
      sites one month after treatment. RESULTS: Six patients (75%) showed immediate
      pain alleviation after treatment, and four of them demonstrated long-lasting
      effect at 6-month follow up (mean VAS reduction; 72.6%). In responders, PPTs in
      medial knee were significantly increased after treatment (Median; pre- 358 kpa vs
      post- 534 kpa, p < 0.0001). There were no adverse side effects or complications
      during and after treatment. CONCLUSIONS: These initial results illustrate the
      safety and efficacy of the newly developing MRgFUS treatment. Significant
      increase of PPTs on treated area showed successful denervation effect on the
      nociceptive nerve terminals. MRgFUS is a promising and innovative procedure for
      noninvasive pain management of knee OA. TRIAL REGISTRATION: Trial Registration:
      UMIN000010193.

PMID- 24034867
TI  - OWL model of clinical trial eligibility criteria compatible with partially-known
      information.
AB  - BACKGROUND: Clinical trials are important for patients, for researchers and for
      companies. One of the major bottlenecks is patient recruitment. This task
      requires the matching of a large volume of information about the patient with
      numerous eligibility criteria, in a logically-complex combination. Moreover, some
      of the patient's information necessary to determine the status of the eligibility
      criteria may not be available at the time of pre-screening. RESULTS: We showed
      that the classic approach based on negation as failure over-estimates rejection
      when confronted with partially-known information about the eligibility criteria
      because it ignores the distinction between a trial for which patient eligibility
      should be rejected and trials for which patient eligibility cannot be asserted.
      We have also shown that 58.64% of the values were unknown in the 286 prostate
      cancer cases examined during the weekly urology multidisciplinary meetings at
      Rennes' university hospital between October 2008 and March 2009.We propose an OWL
      design pattern for modeling eligibility criteria based on the open world
      assumption to address the missing information problem. We validate our model on a
      fictitious clinical trial and evaluate it on two real clinical trials. Our
      approach successfully distinguished clinical trials for which the patient is
      eligible, clinical trials for which we know that the patient is not eligible and
      clinical trials for which the patient may be eligible provided that further
      pieces of information (which we can identify) can be obtained. CONCLUSIONS: OWL
      based reasoning based on the open world assumption provides an adequate framework
      for distinguishing those patients who can confidently be rejected from those
      whose status cannot be determined. The expected benefits are a reduction of the
      workload of the physicians and a higher efficiency by allowing them to focus on
      the patients whose eligibility actually require expertise.

PMID- 24034869
TI  - Critical illness in obstetrics. Preface.

PMID- 24034868
TI  - Innate immunity activation involved in unprotected porcine auto-transplant
      kidneys preserved by naked caspase-3 siRNA.
AB  - BACKGROUND: The naked caspase-3 small interfering RNA (siRNA) infused into the
      renal artery during cold preservation was effective, but did not protect auto
      transplant porcine kidneys with increased inflammation and apoptosis in our
      previous study. The mechanisms involved, in particular, whether siRNA or
      complementary systemic feedback eliciting innate immune responses are worthy to
      be further investigated. METHODS: The protein and mRNA expression of innate
      immunity-related molecules were detected by western blotting and quantitative PCR
      in the tissues previously collected from 48 h auto-transplant kidneys. The donor
      kidneys were retrieved from mini pigs and cold preserved by University of
      Wisconsin solution with/without 0.3 mg caspase-3 siRNA for 24 h. RESULTS: The
      protein level of Toll like receptor (TLR) 3, TLR7, and their main adapters, TRIF
      and MyD88, was up-regulated in the siRNA preserved auto-transplant kidneys. The
      mRNA level of NF-kappaB and c-Jun was increased, as well as pro-inflammatory
      cytokines, including IL-1beta, IL-6, TNF-alpha and interferon (IFN)-alpha, beta
      and gamma. In addition, the non-TLR RNA sensor PKR protein, but not RIG1, was
      also increased in the siRNA preserved auto-transplant kidneys. CONCLUSIONS: The
      activation of innate immunity with amplified inflammatory responses in the
      caspase-3 siRNA preserved auto-transplant kidneys are associated with increased
      TLR3, TLR7 and PKR, which might be due to complementary systemic feedback,
      although persistent actions initiated by short-acting caspase-3 siRNA cannot be
      completely ruled out. These results provided valuable evidence to guide future
      siRNA design and pre-clinic studies.

PMID- 24034870
TI  - Fatal splenic rupture in a previously undiagnosed multiple myeloma:
      morphological, immunophenotypical and molecular cytogenetic analyses.

PMID- 24034871
TI  - Ektacytometry and genetic testing in hereditary red cell membrane disorders.

PMID- 24034872
TI  - Thermal sensations of surgeons during work in surgical gowns.
AB  - Standards for surgical procedures and medical clothing, designed for use in the
      operating theatre, have been gradually developed with the progress in science and
      technology. Standard No. EN 13795:2011, determining the requirements concerning
      materials for production of surgical gowns, was introduced in 2003. It concerns,
      e.g., resistance to microbial penetration. Little attention is given to thermal
      comfort, even though it is well known that thermal discomfort can have an adverse
      effect on the quality and efficiency of work. During a real-life test and
      laboratory tests, 2 male surgeons and 8 male volunteers were asked to describe
      their subjective sensations before and after work. The results of the real-life
      test and the laboratory tests are comparable. They show a clear lack of thermal
      comfort when medical clothing designed for the operating theatre is used. 

PMID- 24034873
TI  - A comparative ergonomics postural assessment of potters and sculptors in the
      unorganized sector in West Bengal, India.
AB  - Potters and sculptors perform their work in very awkward postures. The purpose of
      this study was to analyse these postures. The modified Nordic questionnaire was
      used to analyse musculoskeletal discomfort. Rapid entire body assessment (REBA)
      and rapid upper limb assessment (RULA) were used to evaluate the subjects'
      postures. There were no significant differences between times of discomfort and
      the group of subjects. However, there were significant differences in discomfort
      in different body parts. The analysis indicated that various body postures were
      harmful to the subjects and that there were profound deviations from natural
      curvature of various body parts due to awkward body postures. Ergonomics
      intervention was required to improve the quality of life. 

PMID- 24034874
TI  - Team-based risk assessment and action plans as participatory methods for safe
      patient handling in two Swedish municipal care homes for the elderly.
AB  - OBJECTIVE: We investigated the usefulness of a team-based risk assessment method
      in patient transfer situations in municipal care homes for the elderly. METHODS:
      Evaluation of risk assessment and action plans carried out in 2009. Focus group
      interviews with care givers and one-to-one interviews with managers and
      occupational therapists. RESULTS: The evaluation showed that action plans and
      interventions were developed for each resident with identified risk connected
      with movement/transfer in daily life. Twenty-six patients (28%) of a total number
      of 94 were assigned to the "no risk" category regarding movement/transfer
      situations in daily life. The other 68 patients (72%) required further
      interventions, which were documented in action plans. The interviews indicated
      that the approach of team-based risk assessment and action plans was perceived as
      a functional participatory method aiming to improve daily life and work.
      CONCLUSION: Systematic team-based risk assessment and action plans benefit staff
      as well as residents at care homes for the elderly.

PMID- 24034875
TI  - Ergonomics intervention in an Iranian tire manufacturing industry.
AB  - The aim of an ergonomics intervention conducted in the tire manufacturing
      industry was to improve working conditions. Before the start, a senior manager
      supported the intervention. Participants were divided into teams and trained.
      After observing the overall performance of the teams, over 100 improvements were
      successfully implemented. After the improvements, there were statistically
      significant differences in annual and weekly prevalence of, and annual disability
      reported for, the upper back, the lower back, knees and wrists between before and
      after intervention. The annual prevalence of upper back, lower back, knee and
      wrist complaints decreased from, respectively, 60.3%, 50.2%, 28.9%, 25.8% before
      the intervention to 31.3%, 35.9%, 17.1%, 20.7% after the intervention.
      Significant factors were training and supportive environment based on full
      commitment of the top management. 

PMID- 24034876
TI  - Learning to drive: learners' self-reported cognitive failure level predicts
      driving instructor's observation rating of driving performance.
AB  - OBJECTIVES: Evidence increases that cognitive failure may be used to screen for
      drivers at risk. Until now, most studies have relied on driving learners. This
      exploratory pilot study examines self-report of cognitive failure in driving
      beginners and error during real driving as observed by driving instructors.
      METHODS: Forty-two driving learners of 14 driving instructors filled out a work
      related cognitive failure questionnaire. Driving instructors observed driving
      errors during the next driving lesson. In multiple linear regression analysis,
      driving errors were regressed on cognitive failure with the number of driving
      lessons as an estimator of driving experience controlled. RESULTS: Higher
      cognitive failure predicted more driving errors (p < .01) when age, gender and
      driving experience were controlled in analysis. CONCLUSIONS: Cognitive failure
      was significantly associated with observed driving errors. Systematic research on
      cognitive failure in driving beginners is recommended.

PMID- 24034877
TI  - Occupational risk factors and back injury.
AB  - Twenty-one risk factors affecting laborers in manual materials handling tasks
      were analyzed to determine what, if any, statistically significant relationships
      existed between the factors and the emergence of occupational back injury. The
      statistically significant risk factors (p <= .05) in the univariate analysis were
      determined to be weight lifted per hour (work intensity), trunk twists per hour,
      weight lifted per day, frequency of lift, trunk motions per hour, and trunk
      flexions per hour, with odds ratios (ORs) of 1.28-2.88. In addition, self
      reported discomfort in the neck, middle back, knees, and lower back was
      associated with the outcome of back injury (p <= .05, OR 1.75-2.66). In the
      multivariate analysis, the statistically significant risk factors (p <= .05) were
      weight lifted per hour (work intensity), average weight of lift, and number of
      trunk twists per hour, with ORs of 1.74-4.98. 

PMID- 24034878
TI  - An ergonomics evaluation of certain ATM dimensions.
AB  - Although millions of automatic teller machines (ATMs) are currently used all over
      the world, users of ATMs still have usability problems including inappropriate
      user-ATM interaction, display problems and others. Many developed countries
      already have standards in place for ATMs. However, this is not the case in many
      other countries. This paper aims to assess certain dimensions of ATM machines and
      their suitability for users in Middle Eastern countries using anthropometric
      measurements of the user population taking Saudi Arabia as a case study.
      Dimensions of all ATMs used in Saudi Arabia were measured and compared with
      recommended dimensions based on anthropometric measurements of the user
      population. Results show that there is a mismatch between the dimensions of ATMs
      used in Saudi Arabia and the recommended dimensions based on the user population.
      Practical recommendations are given as to improve the usability of ATMs in Saudi
      Arabia and other Middle Eastern countries. 

PMID- 24034879
TI  - On evaluation and localization of auditory warning devices for adequate
      audibility.
AB  - This paper presents an analytic procedure to assist safety practitioners in
      evaluating the audibility of an existing auditory warning system in their
      workplaces. Two alarm location models are described: (a) a model with an unknown
      signal sound level, and (b) a model with a known signal sound level. A heuristic
      algorithm to determine a minimum number of alarm devices and their locations so
      that the warning signals can be clearly heard by workers is also proposed. The
      algorithm considers the ambient noise level, noise levels generated by individual
      machines, locations where workers are likely to be present, and noise levels at
      worker locations. From the numerical examples and the computation experiment,
      both the optimization and heuristic approaches yield solutions that satisfy the
      15-dBA constraints. The heuristic approach is efficient in solving large alarm
      location problems due its capability to find near-optimal solutions within
      reasonable computation time. 

PMID- 24034880
TI  - A vibroacoustic diagnostic system as an element improving road transport safety.
AB  - Mechanical defects of a vehicle driving system can be dangerous on the road.
      Diagnostic systems, which monitor operations of electric and electronic elements
      and devices of vehicles, are continuously developed and improved, while defects
      of mechanical systems are still not managed properly. This article proposes
      supplementing existing on-board diagnostics with a system of diagnosing selected
      defects to minimize their impact. It presents a method of diagnosing mechanical
      defects of the engine, gearbox and other elements of the driving system on the
      basis of a model of the vibration signal obtained adaptively. This method is
      suitable for engine valves, engine head gasket, main gearbox, joints, etc. 

PMID- 24034881
TI  - Ergonomics assessment of composite ballistic inserts for bullet- and fragment
      proof vests.
AB  - Personal protective equipment worn by uniformed services (e.g., the police and
      the military) must ensure protection against bodily injuries. However, a high
      degree of protection is always associated with significant discomfort. This
      article presents the results of an assessment of the ergonomics parameters of new
      special purpose products, ballistic inserts with improved ballistic resistance,
      and an assessment of the impact of the burden related to their use on the
      psychomotor performance of the subjects. An obstacle course and subjective
      ergonomics assessment questionnaires were used in tests. Thermal discomfort was
      also assessed. Psychological testing included tests enabling an assessment of the
      subjects' cognitive and psychomotor performance, and a subjective assessment of
      mental load. The tests did not show any decrease in the comfort of use of the new
      inserts with improved ballistic resistance compared to the inserts currently
      used. 

PMID- 24034882
TI  - Effect of external load at varying hand positions on perceived discomfort.
AB  - The purpose of this study was to assess the effect of external load at varying
      hand positions on discomfort, and to provide a new classification of external
      load. An experiment was carried out in which 16 postures with an external load of
      0, 1.5, 3 kg were tested. The postures were controlled by 2 independent variables
      of hand distance and hand height. The subjects were instructed to rate their
      perceived discomfort with magnitude estimation after holding a given posture for
      1 min. Analysis of variance (ANOVA) exhibited that the main effects of the 3
      independent variables were statistically significant for discomfort. Discomfort
      increased linearly with external load and hand distance. Hand height showed a
      quadratic relation with discomfort, which exhibited a slightly different trend
      from hand distance and external load. Based on the results, a new classification
      of external load was proposed with 3 classes grouped by perceived discomfort. 

PMID- 24034883
TI  - Working life of women with disabilities--a review.
AB  - The aim of this study was to present the situation of women with disabilities on
      the labour market. Women with disabilities suffer from social and professional
      discrimination. They are discriminated because of their gender and disability.
      The Q1 Labour Force Participation Study (2013) showed that, in Poland, labour
      force participation for men and women with disabilities was 29.4% and 14.7%,
      respectively, while the unemployment rate was 16.1% for men and 17.2% for women.
      Quarterly information on employment, unemployment and economic inactivity was
      gathered from a Labour Force Survey in the first quarter of 2013; data from the
      Ministry of Labour and Social Policy were also included. The participants of the
      survey were 15 years old or older; they were members of a sample household. The
      methodology was based on definitions recommended by the International Labour
      Office and Eurostat. It is important that women with disabilities are
      substantially less professionally active, while the unemployment rate for them is
      only slightly higher. 

PMID- 24034884
TI  - The impact of mobile data terminal use on posture and low-back discomfort when
      combined with simulated prolonged driving in police cruisers.
AB  - The introduction of mobile computing within a constrained vehicle environment has
      led to changes in the task demands of occupational groups such as professional
      drivers and law enforcement officers. The purpose of this study was to examine
      how mobile data terminal (MDT) use interacts with prolonged driving to induce
      postural changes or low-back discomfort. Eighteen participants (9 male, 9 female)
      completed two 120-min simulated driving sessions. Time-varying lumbar spine and
      pelvis postures, seat pan interface pressures and ratings of perceived discomfort
      were recorded at 15-min intervals. The introduction of a computer interface
      decreased pelvic posterior rotation by an average of 15 degrees  with respect to
      upright standing and increased peak average discomfort in the neck (5.9 mm), left
      shoulder (6.8 mm), midback (10.9 mm), low back (10.6 mm) and pelvis (11.5 mm)
      compared to driving alone. The incorporation of mobile computing warrants
      consideration in the design of vehicle work environments. 

PMID- 24034885
TI  - Causation of severe and fatal accidents in the manufacturing sector.
AB  - The main purpose of this paper is to identify the most frequent causes of
      accidents in the manufacturing sector in Andalusia, Spain, to help safety
      practitioners in the task of prioritizing preventive actions. Official accident
      investigation reports are analyzed. A causation pattern is identified with the
      proportion of causes of each of the different possible groups of causes. We found
      evidence of a differential causation between slight and nonslight accidents. We
      have also found significant differences in accident causation depending on the
      mechanism of the accident. These results can be used to prioritize preventive
      actions to combat the most likely causes of each accident mechanism. We have also
      done research on the associations of certain latent causes with specific active
      (immediate) causes. These relationships show how organizational and safety
      management can contribute to the prevention of active failures. 

PMID- 24034886
TI  - Occupational safety and health status of sanitation workers in urban areas: a
      pilot study from Wuhan, China.
AB  - Sanitation workers' workload increases quickly with rapid urbanization, but there
      is almost no evidence or policy recommendations for their management in
      developing countries. This study describes the health status and occupational
      protection of sanitation workers; it also explores risk factors related to their
      health status in Wuhan City, China. Three hundred and eighty-five sanitation
      workers from 54 streets of Wuhan were surveyed. Their prevalence of 2-week
      illness and arthritis was relatively higher than in the general population in
      China. Findings related to occupational protection showed that both sanitation
      workers (users) and their managers (providers) neglected the role of low-cost
      protection measures, especially masks, soap/hand sanitizer and prejob training
      (use rate of 7.27%, 26.75% and 43.64%, respectively). High-intensity workload was
      an important risk factor for 2-week illness, and prejob training was an important
      protective factor against arthritis. 

PMID- 24034887
TI  - Cognitive reserve in Parkinson's disease: a systematic review and meta-analysis.
AB  - BACKGROUND: The concept of cognitive reserve is proposed to explain the mismatch
      between the degree of pathological changes and their clinical manifestations and
      has been used to help understand the variation in the rate of cognitive decline
      and the development of dementias. It is not clear whether this concept applies to
      cognitive performance, cognitive decline and dementia in Parkinson's disease
      (PD). METHODS: A systematic review was conducted using the most commonly
      described proxies for cognitive reserve of education, occupation and leisure
      activities. Thirty four papers were found on education and cognition in PD but
      there were no studies of the other proxies of reserve. A random effects meta
      analysis was used to assess the associations between education and cross
      sectional cognitive assessments, longitudinal global cognitive decline and a long
      term dementia diagnosis. RESULTS: There was a significant association between
      higher education and cross-sectional performance of MMSE, global cognition, mild
      cognitive impairment, attention, executive function, visuospatial function and
      memory. There was a small but significant association between higher education
      and a reduced rate of cognitive decline. There was no association with a final
      dementia diagnosis. There was not enough information to perform an analysis on
      the rate and timing of transition to dementia. CONCLUSIONS: Higher levels of
      education are associated with significantly better cognitive performance and a
      small but significant slowing in cognitive decline but are not associated with a
      reduction in long-term dementia in PD. More detailed, standardized, longitudinal
      studies are required to study conclusively the effects cognitive reserve in PD.

PMID- 24034888
TI  - The oxygen-tolerant and NAD+-dependent formate dehydrogenase from Rhodobacter
      capsulatus is able to catalyze the reduction of CO2 to formate.
AB  - The formate dehydrogenase from Rhodobacter capsulatus (RcFDH) is an oxygen
      tolerant protein with an (alphabetagamma)2 subunit composition that is localized
      in the cytoplasm. It belongs to the group of metal and NAD(+)-dependent FDHs with
      the coordination of a molybdenum cofactor, four [Fe4S4] clusters and one [Fe2S2]
      cluster associated with the alpha-subunit, one [Fe4S4] cluster and one FMN bound
      to the beta-subunit, and one [Fe2S2] cluster bound to the gamma-subunit. RcFDH
      was heterologously expressed in Escherichia coli and characterized. Cofactor
      analysis showed that the bis-molybdopterin guanine dinucleotide cofactor is bound
      to the FdsA subunit containing a cysteine ligand at the active site. A turnover
      rate of 2189 min(-1) with formate as substrate was determined. The back reaction
      for the reduction of CO2 was catalyzed with a k(cat) of 89 min(-1). The
      preference for formate oxidation shows an energy barrier for CO2 reduction of the
      enzyme. Furthermore, the FMN-containing and [Fe4S4]-containing beta-subunit
      together with the [Fe2S2]-containing gamma-subunit forms a diaphorase unit with
      activities for both NAD(+) reduction and NADH oxidation. In addition to the
      structural genes fdsG, fdsB, and fdsA, the fds operon in R. capsulatus contains
      the fdsC and fdsD genes. Expression studies showed that RcFDH is only active when
      both FdsC and FdsD are present. Both proteins are proposed to be involved in bis
      molybdopterin guanine dinucleotide modification and insertion into RcFDH.

PMID- 24034889
TI  - Antioxidant response versus selenium accumulation in the liver and kidney of the
      Siberian sturgeon (Acipenser baeri).
AB  - The aim of this study was to examine the effects of selenium on concentrations of
      metabolites and enzyme activities acting as antioxidant markers in liver and
      kidney of Siberian sturgeon Acipenser baeri. Sturgeons were fed selenium cysteine
      for 30 and 60 d at 1.25, 5, 20mg Sekg(-1). Selenium level in the control feed was
      0.32 mg kg(-1). Se concentration was measured in liver, kidney and muscle of
      every specimen. Sturgeon accumulated Se in tissues with a clear dose-response
      relationship and the highest Se concentration was recorded in liver. This outcome
      is lined up with the findings obtained on the antioxidant markers evaluated in
      both tissues, and in which a dose-response for several biomarkers was recorded in
      liver. The superoxide dismutase activity in Se-treated fish was generally
      induced, while catalase activity was lower in liver or unaltered in kidney. The
      concentrations of glutathione S-transferase, glutathione reductase and total
      glutathione responded differently for both tissues and were induced in a
      different way at both endpoints. No changes of glyoxalase I activity were noted
      for both Se-treated tissues, while for glyoxalase II enzyme in liver a dose
      related pattern was found showing a reversible effect (decreased and increased
      counteractive response) only in the 5 mg kg(-1) group. Moreover, the highest Se
      concentrations did not cause marked changes in malondialdehyde levels of liver
      and kidney. The enhancement of glutathione peroxidase activity in Se-treated
      sturgeon might have prevented the lipid peroxidation in both tissues, providing
      to the Siberian sturgeon a great defense ability versus the prooxidant effect of
      selenium.

PMID- 24034890
TI  - Mechanistic approach to multi-element isotope modeling of organic contaminant
      degradation.
AB  - We propose a multi-element isotope modeling approach to simultaneously predict
      the evolution of different isotopes during the transformation of organic
      contaminants. The isotopic trends of different elements are explicitly simulated
      by tracking position-specific isotopologues that contain the isotopes located at
      fractionating positions. Our approach is self-consistent and provides a
      mechanistic description of different degradation pathways that accounts for the
      influence of both primary and secondary isotope effects during contaminant
      degradation. The method is particularly suited to quantitatively describe the
      isotopic evolution of relatively large organic contaminant molecules. For such
      compounds, an integrated approach, simultaneously considering all possible
      isotopologues, would be impractical due to the large number of isotopologues. We
      apply the proposed modeling approach to the degradation of toluene, methyl tert
      butyl ether (MTBE) and nitrobenzene observed in previous experimental studies.
      Our model successfully predicts the multi-element isotope data (both 2D and 3D),
      and accurately captures the distinct trends observed for different reaction
      pathways. The proposed approach provides an improved and mechanistic methodology
      to interpret multi-element isotope data and to predict the extent of multi
      element isotope fractionation that goes beyond commonly applied modeling
      descriptions and simplified methods based on the ratio between bulk enrichment
      factors or on linear regression in dual-isotope plots. 

PMID- 24034891
TI  - The non-target organism Caenorhabditis elegans withstands the impact of
      sulfamethoxazole.
AB  - The widespread usage of antibiotics in agriculture leads to releases into the
      environment, but there is insufficient knowledge of the side-effects on non
      target organisms. Therefore, we investigated the effects of the sulfonamide
      antibiotic sulfamethoxazole (SMX) on Caenorhabditis elegans at phenotypic,
      biochemical and molecular biological levels. Multiple endpoints, including life
      history traits, thermal stress resistance and lipid peroxidation, as well as gene
      expression profiles, were determined after exposure of the nematodes to SMX. In
      contrast to expectations, SMX prolonged the lifespan and increased both the body
      size and pharynx pumping rate. On the other hand, SMX delayed reproductive timing
      and caused lipid peroxidation. The total number of offspring and thermal stress
      resistance were unaffected. The up-regulation of hsp-16.1 indicated stress in
      general and the increased lipid peroxidation oxidative stress in particular. This
      oxidative stress indicated that mitohormesis was the likely cause of the
      longevity and that enhanced pumping frequency was probably the reason for the
      increased growth. The sole adverse effect was delayed initial reproduction. This
      delay, however, can be crucial for r-strategists, such as the bacterivorous model
      animal used, in sustaining their populations in the environment in the presence
      of predators. Bacterivorous animals, in turn, are essential to maintaining
      nutrient recycling via the microbial loop. 

PMID- 24034892
TI  - Assessing benzene-induced toxicity on wild type Euglena gracilis Z and its mutant
      strain SMZ.
AB  - Benzene is a representative member of volatile organic compounds and has been
      widely used as an industrial solvent. Groundwater contamination of benzene may
      pose risks to human health and ecosystems. Detection of benzene in the
      groundwater using chemical analysis is expensive and time consuming. In addition,
      biological responses to environmental exposures are uninformative using such
      analysis. Therefore, the aim of this study was to employ a microorganism, Euglena
      gracilis (E. gracilis) as a putative model to monitor the contamination of
      benzene in groundwater. To this end, we examined the wild type of E. gracilis Z
      and its mutant form, SMZ in their growth rate, morphology, chlorophyll content,
      formation of reactive oxygen species (ROS) and DNA damage in response to benzene
      exposure. The results showed that benzene inhibited cell growth in a dose
      response manner up to 48 h of exposure. SMZ showed a greater sensitivity compared
      to Z in response to benzene exposure. The difference was more evident at lower
      concentrations of benzene (0.005-5 MUM) where growth inhibition occurred in SMZ
      but not in Z cells. We found that benzene induced morphological changes,
      formation of lipofuscin, and decreased chlorophyll content in Z strain in a dose
      response manner. No significant differences were found between the two strains in
      ROS formation and DNA damage by benzene at concentrations affecting cell growth.
      Based on these results, we conclude that E. gracilis cells were sensitive to
      benzene-induced toxicities for certain endpoints such as cell growth rate,
      morphological change, depletion of chlorophyll. Therefore, it is a potentially
      suitable model for monitoring the contamination of benzene and its effects in the
      groundwater.

PMID- 24034893
TI  - Effect of compost and biodegradable chelate addition on phytoextraction of copper
      by Oenothera picensis grown in Cu-contaminated acid soils.
AB  - Oenothera picensis plants (Fragrant Evening Primrose) grow in the acid soils
      contaminated by Cu smelting in the coastal region of central Chile. We evaluated
      the effects of compost, at application rate of 5 kg m(-2), and biodegradable
      chelate MGDA (methylglycinediacetic acid), at application rate of 6 mmol plant(
      1), on Cu phytoextraction by O. picensis, in field plots. No significant
      differences were found between treatments regarding aboveground biomass, shoot Cu
      concentrations and Cu phytoextraction of O. picensis. This lack of effects of the
      treatments was provoked by the large variability of soil properties, prior to
      applying of the treatments. The shoot Cu concentration in O. picensis positively
      and significantly correlated to exchangeable Cu concentration in the soil.
      Likewise, the aboveground biomass of O. picensis positively and significantly
      correlated to soil organic matter content. The Cu phytoextraction by O. picensis,
      in turn, positively and significantly correlated to both variables, i.e.
      exchangeable Cu concentration and organic matter content. The average Cu
      phytoextraction was 1.1 mg plant(-1), which is equivalent to 90 g ha(-1) at
      planting rate of 8 plants m(-2). In the chelate treatment, Cu phytoextraction was
      2.6+/-2.1 mg plant(-1), which is equivalent to 212+/-171 g ha(-1) at planting
      rate of 8 plants m(-2).

PMID- 24034894
TI  - Study on enhanced denitrification using particulate organic matter in membrane
      bioreactor by mechanism modeling.
AB  - Particulate organic matter (POM) in wastewater is a potential denitrification
      carbon source, while the optimal operational mode using denitrification mechanism
      with POM is still unclear in wastewater treatment plants. In this work, we
      investigated the denitrification rates (DNRs) in a full-scale membrane bioreactor
      (MBR) coupled with two-stage pre-anoxic (pre-AN), and then evaluated the POM
      denitrification efficiency using mechanism modeling. The results indicate that
      POM related fraction accounted for the majority of the obtained specific DNR of
      1.39+/-0.46mgNg(-1) MLVSS h(-1) in the second pre-AN without available soluble
      carbon source. The modeling approaches with calibration and validation procedures
      estimated a high residual POM concentration of 0.17g COD g(-1) MLVSS in the
      activated sludge, which provided specific DNR of 1.14mgNg(-1) MLVSS h(-1). High
      POM retention time in the reactor was the result of high solid retention time
      used in the MBR. In particular, post-AN of high biomass concentration could
      provide the highest POM denitrification efficiency in MBR. The MBR process
      combined with additional sludge reduction technology could further enhance
      denitrification by POM. 

PMID- 24034895
TI  - In vivo endocrine effects of naphthenic acids in fish.
AB  - Oil pollution from various sources, including exploration, production and
      transportation, is a growing global concern. The highest toxicity of hydrocarbon
      pollutants is associated with the water-soluble phase compounds, including
      naphthenic acids, a known component found in all hydrocarbon deposits. Recently,
      naphthenic acids (NAs) have shown estrogenic and anti-androgenic effects in
      vitro. For this reason we investigated the potential effects of two commercial
      mixtures of naphthenic acids on fish in vivo, using the three-spined stickleback
      (Gasterosteus aculeatus) as a model species. Anti-androgenic and estrogenic
      properties of tested compounds were evaluated using the androgenized female
      stickleback screen (AFSS) and a variant of the 21-d fish screen (TG230)
      respectively. One-dimensional gas chromatography-mass spectrometry (GC-MS) showed
      that the complex commercial NAs mixtures were dominated by acyclic carboxylic
      acids. In one experiment (freshwater) we found a clear effect of NA exposure on
      spiggin levels; this was contrary to our hypothesis since NAs enhanced the
      androgenic potency of DHT (when co-administered) without inducing spiggin when
      tested in the absence of DHT. Exposure to NAs did not have a statistically
      significant effect on vitellogenin (Vtg) production in male stickleback, although
      the Vtg responses were increasing with increasing exposure concentrations. This
      study shows that in contrast to previous in vitro data, NAs did not exhibit
      either estrogenic or anti-androgenic properties in vivo, at the concentrations
      tested. On the contrary, at least in freshwater, NAs appear to have an overall
      androgenic effect that is not mediated via the androgen receptor involved in
      spiggin synthesis. Possible reasons for this discrepancy between in vitro and in
      vivo results as well as between our studies are discussed. 

PMID- 24034896
TI  - Inflammatory myofibroblastic tumor with RANBP2 and ALK gene rearrangement: a
      report of two cases and literature review.
AB  - Inflammatory myofibroblastic tumors (IMTs) are categorized as intermediate
      biologic neoplasms, whereas IMTs with genetic features of ran-binding protein 2
      (RANBP2) and anaplastic lymphoma kinase (ALK) rearrangement (IMT-RAs) are
      possibly related to a more aggressive clinical course. However, fewer than 10
      cases of IMT-RA have been reported to date. Herein, we present 2 new cases of IMT
      RA in which both tumors recurred quickly after primary surgery; one patient died
      3 months later from the disease, and the other patient has been living with the
      disease for 12 months. IMT-RAs are characterized by noncohesive epithelioid and
      rounded tumoral cell morphology, commonly derived from pelvic and peritoneal
      cavities, and frequently show larger tumor sizes. The relation between the
      clinicopathologic features and poor prognosis of IMT-RA is discussed. VIRTUAL
      SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/3314123381007714.

PMID- 24034897
TI  - Is Atyaephyra desmarestii a useful candidate for lethal and sub-lethal toxicity
      tests on pharmaceutical compounds?
AB  - Single and mixture toxicity tests on three pharmaceutical compounds, Diclofenac
      (DF), Ibuprofen (IB) and Carbamazepine (CBZ), were carried out with the
      freshwater shrimp Atyaephyra desmarestii. Lethal and sublethal responses were
      analyzed for single compounds. Lethal concentrations (LC50) obtained for each
      individual compound, after 96 h of exposure, were 6.3 mg L(-1) for DF, 13.3 mg L(
      1) for IB and 94.3 mg L(-1) for CBZ. The selected sublethal endpoints of food
      ingestion, osmoregulatory capacity and respiration rates were not affected by the
      exposures to environmentally-relevant concentrations. Based on mortality data
      obtained, the predictive no effect concentration (PNEC) was calculated for each
      of the compounds, and compared with predicted environmental concentrations (PEC)
      reported in surface waters. The environmental risk of each compound was estimated
      as the ratio between PEC/PNEC, and indicated that IB could represent a medium
      risk in freshwater environments. Additionally, binary and ternary mixture
      toxicity assays of the selected compounds were carried out. The data obtained was
      applied to two predictive toxicity models: Concentration Addition (CA) and
      Independent Action (IA). Finally, risk assessment was estimated using risk
      quotients (RQ) for the compound mixtures based on EC50 and LC50 values.

PMID- 24034898
TI  - Comparative genomics of emerging pathogens in the Candida glabrata clade.
AB  - BACKGROUND: Candida glabrata follows C. albicans as the second or third most
      prevalent cause of candidemia worldwide. These two pathogenic yeasts are
      distantly related, C. glabrata being part of the Nakaseomyces, a group more
      closely related to Saccharomyces cerevisiae. Although C. glabrata was thought to
      be the only pathogenic Nakaseomyces, two new pathogens have recently been
      described within this group: C. nivariensis and C. bracarensis. To gain insight
      into the genomic changes underlying the emergence of virulence, we sequenced the
      genomes of these two, and three other non-pathogenic Nakaseomyces, and compared
      them to other sequenced yeasts. RESULTS: Our results indicate that the two new
      pathogens are more closely related to the non-pathogenic N. delphensis than to C.
      glabrata. We uncover duplications and accelerated evolution that specifically
      affected genes in the lineage preceding the group containing N. delphensis and
      the three pathogens, which may provide clues to the higher propensity of this
      group to infect humans. Finally, the number of Epa-like adhesins is specifically
      enriched in the pathogens, particularly in C. glabrata. CONCLUSIONS: Remarkably,
      some features thought to be the result of adaptation of C. glabrata to a
      pathogenic lifestyle, are present throughout the Nakaseomyces, indicating these
      are rather ancient adaptations to other environments. Phylogeny suggests that
      human pathogenesis evolved several times, independently within the clade. The
      expansion of the EPA gene family in pathogens establishes an evolutionary link
      between adhesion and virulence phenotypes. Our analyses thus shed light onto the
      relationships between virulence and the recent genomic changes that occurred
      within the Nakaseomyces. SEQUENCE ACCESSION NUMBERS: Nakaseomyces delphensis:
      CAPT01000001 to CAPT01000179Candida bracarensis: CAPU01000001 to
      CAPU01000251Candida nivariensis: CAPV01000001 to CAPV01000123Candida castellii:
      CAPW01000001 to CAPW01000101Nakaseomyces bacillisporus: CAPX01000001 to
      CAPX01000186.

PMID- 24034900
TI  - Rapid and simultaneous detection of the chlorhexidine and mupirocin resistance
      genes qacA/B and mupA in clinical isolates of methicillin-resistant
      Staphylococcus aureus.
AB  - We describe a real-time PCR-based assay capable of simultaneously detecting femA
      (Staphylococcus aureus-specific), mecA (methicillin resistance), qacA/B
      (chlorhexidine tolerance), and mupA (high-level mupirocin resistance) from
      bacterial cells in less than 90 minutes. The assay was validated with 1968
      clinical MRSA submitted to a surveillance network. 

PMID- 24034901
TI  - Reactive arthritis associated with Mycoplasma genitalium urethritis.
AB  - Mycoplasma genitalium is an important cause of sexually transmitted infections
      that is gaining recognition and is an independent cause of acute and chronic
      nongonococcal urethritis in men. M. genitalium has been implicated as a possible
      causative factor in reactive arthritis. We report a case of reactive arthritis
      complicating M. genitalium urethritis in an HLA-B27-positive patient. 

PMID- 24034899
TI  - Proceedings of the Fourth International Workshop on Advances in
      Electrocorticography.
AB  - The Fourth International Workshop on Advances in Electrocorticography (ECoG)
      convened in New Orleans, LA, on October 11-12, 2012. The proceedings of the
      workshop serves as an accurate record of the most contemporary clinical and
      experimental work on brain surface recording and represents the insights of a
      unique multidisciplinary ensemble of expert clinicians and scientists.
      Presentations covered a broad range of topics, including innovations in passive
      functional mapping, increased understanding of pathologic high-frequency
      oscillations, evolving sensor technologies, a human trial of ECoG-driven brain
      machine interface, as well as fresh insights into brain electrical stimulation. 

PMID- 24034902
TI  - Comparison of MALDI-TOF MS and VITEK 2 system for laboratory diagnosis of
      Granulicatella and Abiotrophia species causing invasive infections.
AB  - Granulicatella and Abiotrophia spp. were known as nutritionally variant
      streptococci (NVS). Such strains have caused major diagnostic difficulties due to
      fastidious culturing and unspecific colony morphology. The present study is aimed
      at comparing the performance of laboratory available diagnostic methods for NVS
      isolates and determining the antimicrobial susceptibility of these isolates.
      Fourteen clinical invasive isolates, consisting of 10 Granulicatella adiacens, 1
      Granulicatella elegans, and 3 Abiotrophia defectiva were in parallel analyzed by
      2 matrix-assisted laser desorption ionization-time of flight mass spectrometry
      (MALDI-TOF MS) systems, i.e., Bruker MS and Vitek MS, as well as Vitek 2 for the
      species determination. 16S rRNA gene sequencing was applied as a reference
      method. The Vitek MS gave correct identification for all 14 isolates. The Bruker
      MS could correctly identify 8/10 G. adiacens, 0/1 G. elegans, and 3/3 A.
      defectiva isolates at the first analysis occasion, and all 14 isolates became
      identifiable after repeated tests. The Vitek 2 system could identify 6/10 G.
      adiacens, 1/1 G. elegans, and 2/3 A. defectiva isolates at the species level.
      Antimicrobial susceptibilities of 11 antibiotics were determined by Etest.
      Resistance against ciprofloxacin, ceftriaxone, rifampicin, and tetracycline were
      observed in 4, 10, 4, and 1 isolates, respectively. In conclusion, MALDI-TOF MS
      is a useful tool for the rapid diagnosis of NVS. Phenotypic testing by Vitek 2 is
      only partially effective for the accurate identification of such strains. The
      emergence of resistant NVS isolates indicates the necessity of monitoring
      antimicrobial susceptibilities of such uncommon pathogens. 

PMID- 24034903
TI  - Solid state NMR and protein-protein interactions in membranes.
AB  - Solid state NMR spectroscopy has evolved rapidly in recent years into an
      excellent tool for the characterization of membrane proteins and their complexes.
      In the past few years it has also become clear that the structure of membrane
      proteins, especially helical membrane proteins is determined, in part, by the
      membrane environment. Therefore, the modeling of this environment by a liquid
      crystalline lipid bilayer for solid state NMR has generated a unique tool for the
      characterization of native conformational states, local and global dynamics, and
      high-resolution structure for these proteins. Protein-protein interactions can
      also benefit from this solid state NMR capability to characterize membrane
      proteins in a native-like environment. These complexes take the form of
      oligomeric structures and hetero-protein interactions both with water-soluble
      proteins and other membrane proteins. 

PMID- 24034904
TI  - rAAV-mediated overexpression of TGF-beta stably restructures human osteoarthritic
      articular cartilage in situ.
AB  - BACKGROUND: Therapeutic gene transfer is of significant value to elaborate
      efficient, durable treatments against human osteoarthritis (OA), a slow,
      progressive, and irreversible disorder for which there is no cure to date.
      METHODS: Here, we directly applied a recombinant adeno-associated virus (rAAV)
      vector carrying a human transforming growth factor beta (TGF-beta) gene sequence
      to primary human normal and OA chondrocytes in vitro and cartilage explants in
      situ to monitor the stability of transgene expression and the effects of the
      candidate pleiotropic factor upon the regenerative cellular activities over time.
      RESULTS: Efficient, prolonged expression of TGF-beta achieved via rAAV gene
      transfer enhanced both the proliferative, survival, and anabolic activities of
      cells over extended periods of time in all the systems evaluated (at least for 21
      days in vitro and for up to 90 days in situ) compared with control (reporter)
      vector delivery, especially in situ where rAAV-hTGF-beta allowed for a durable
      remodeling of OA cartilage. Notably, sustained rAAV production of TGF-beta in OA
      cartilage advantageously reduced the expression of key OA-associated markers of
      chondrocyte hypertrophic and terminal differentiation (type-X collagen, MMP-13,
      PTHrP, beta-catenin) while increasing that of protective TIMPs and of the TGF
      beta receptor I in a manner that restored a favorable ALK1/ALK5 balance. Of note,
      the levels of activities in TGF-beta-treated OA cartilage were higher than those
      of normal cartilage, suggesting that further optimization of the candidate
      treatment (dose, duration, localization, presence of modulating co-factors) will
      most likely be necessary to reproduce an original cartilage surface in relevant
      models of experimental OA in vivo without triggering potentially adverse effects.
      CONCLUSIONS: The present findings show the ability of rAAV-mediated TGF-beta gene
      transfer to directly remodel human OA cartilage by activating the biological,
      reparative activities and by regulating hypertrophy and terminal differentiation
      in damaged chondrocytes as a potential treatment for OA or for other disorders of
      the cartilage that may require transplantation of engineered cells.

PMID- 24034906
TI  - Health economics education in undergraduate medical training: introducing the
      health economics education (HEe) website.
AB  - In the UK, the General Medical Council clearly stipulates that upon completion of
      training, medical students should be able to discuss the principles underlying
      the development of health and health service policy, including issues relating to
      health economics. In response, researchers from the UK and other countries have
      called for a need to incorporate health economics training into the undergraduate
      medical curricula. The Health Economics education website was developed to
      encourage and support teaching and learning in health economics for medical
      students. It was designed to function both as a forum for teachers of health
      economics to communicate and to share resources and also to provide instantaneous
      access to supporting literature and teaching materials on health economics. The
      website provides a range of free online material that can be used by both health
      economists and non-health economists to teach the basic principles of the
      discipline. The Health Economics education website is the only online education
      resource that exists for teaching health economics to medical undergraduate
      students and it provides teachers of health economics with a range of
      comprehensive basic and advanced teaching materials that are freely available.
      This article presents the website as a tool to encourage the incorporation of
      health economics training into the undergraduate medical curricula. 

PMID- 24034905
TI  - Worse limb prognosis for indirect versus direct endovascular revascularization
      only in patients with critical limb ischemia complicated with wound infection and
      diabetes mellitus.
AB  - OBJECTIVES: To investigate factors in patients with critical limb ischemia (CLI)
      and isolated infrapopliteal lesions that adversely affect outcomes of
      endovascular therapy (EVT) with or without angiosome-oriented revascularization.
      METHODS: This was a retrospective multicenter study. We used a database of 718
      consecutive CLI patients (70 +/- 11 years, 75% diabetics, 68% on hemodialysis,
      24% Rutherford class 6) with ischemic tissue loss due to isolated infrapopliteal
      lesions undergoing primary EVT. Primary outcome was MALE (major adverse limb
      event). Association between indirect EVT (recanalization of a non-angiosome-based
      artery) and outcome was assessed by Cox proportional hazard regression model.
      RESULTS: C-reactive protein (CRP) level was >3 mg/dL in 32% of cases. Indirect
      EVT (in 307 CLI patients, 43%), was associated with MALE (p = .04, hazard ratio
      [95% confidence interval] 1.25 [1.01, 1.55]), and interacted with CRP >3 mg/dL (p
      < .004) but not with other baseline characteristics. Indirect EVT with CRP >3
      mg/dL had higher MALE risk (HR 2.08), and interacted with diabetes mellitus (DM)
      presence. Indirect EVT with CRP >3 mg/dL and DM had higher MALE risk (HR 2.17).
      CONCLUSION: Limb prognosis was equivalent for direct and indirect endovascular
      revascularization except in the presence of both diabetes and wound infection,
      when indirect revascularization has a poorer outcome.

PMID- 24034907
TI  - Evaluation of a patient specific femoral alignment guide for hip resurfacing.
AB  - A novel alternative to conventional instrumentation for femoral component
      insertion in hip resurfacing is a patient specific, computed tomography based
      femoral alignment guide. A benchside study using cadaveric femora was performed
      comparing a custom alignment guide to conventional instrumentation and computer
      navigation. A clinical series of twenty-five hip resurfacings utilizing a custom
      alignment guide was conducted by three surgeons experienced in hip resurfacing.
      Using cadaveric femora, the custom guide was comparable to conventional
      instrumentation with computer navigation proving superior to both. Clinical
      femoral component alignment accuracy was 3.7 degrees  and measured within +/- 5
      degrees  of plan in 20 of 24 cases. Patient specific femoral alignment guides
      provide a satisfactory level of accuracy and may be a better alternative to
      conventional instrumentation for initial femoral guidewire placement in hip
      resurfacing.

PMID- 24034908
TI  - Management of an incident of failed sterilization of surgical instruments in a
      dental clinic in Hong Kong.
AB  - BACKGROUND/PURPOSE: We describe an investigation of an incident of failed
      sterilization procedure in a dental clinic. We aim to illustrate the principles
      in performing such investigations and to highlight some of the important
      checkpoints in sterilization procedures. METHODS: In response to this incident,
      proper sterilization of all equipment was performed immediately. On-site
      investigation was conducted by the investigation panel to identify the cause and
      risks, to coordinate post-exposure management in affected patients, and to make
      recommendations to prevent similar occurrence of such incidents in the future.
      RESULTS: The incident was due to a rare lapse of monitoring during the
      autoclaving cycle. A total of 127 sources and 250 exposed patients were
      identified within 24 hours of the discovery of the incident for risk assessment
      and testing for blood-borne viruses, including hepatitis B virus (HBV), hepatitis
      C virus (HCV), and human immunodeficiency virus (HIV). A protocol was devised to
      manage the exposed patients against HBV, HCV, and HIV. Immunization and
      hyperimmune globulin for hepatitis B, and tetanus toxoids were given to the
      exposed patients where indicated. Exposed patients were followed-up for 6 months.
      We came to the decision that dating of instrument packages and signed
      documentation of each autoclave printout, color change of chemical indicators of
      each load and daily autoclave performance should be made mandatory with immediate
      effect. CONCLUSION: Rapid response is extremely crucial in minimizing the impact
      of this incident and relieving the anxiety of the affected patients. Proper
      recording and documentation of autoclave cycles and regular auditing should be
      enforced to prevent similar incidents.

PMID- 24034909
TI  - [Application of neurally adjusted ventilatory assist in preterm infants with
      respiratory distress syndrome].
AB  - OBJECTIVE: To observe the effects of neurally adjusted ventilatory assist (NAVA)
      on the patient-ventilator synchrony, gas exchange, and ventilatory parameters in
      preterm infants with respiratory distress syndrome (RDS) during mechanical
      ventilation. METHODS: Ten preterm infants with RDS received mechanical
      ventilation in NAVA mode for 60 minutes and in synchronized intermittent
      mandatory ventilation (SIMV) mode for 60 minutes, and the two modes were given in
      a random order. The vital signs, patient-ventilator synchrony, blood gas values,
      and ventilatory parameters were compared between the two ventilation modes.
      RESULTS: Inspiratory trigger delay was significantly shorter with NAVA than with
      SIMV (P<0.05). There were no significant differences in arterial pH, PaCO2, PaO2
      and PaO2/FiO2 between the two modes. The spontaneous respiratory rate, peak
      inspiratory pressure (PIP), electrical activity of the diaphragm and work of
      breathing were significantly lower in NAVA than in SIMV (P<0.05). CONCLUSIONS:
      Compared with SIMV, NAVA appears to improve patient-ventilator synchrony,
      decrease PIP, and reduce diaphragmatic muscle load and work of breathing in
      preterm infants with RDS during mechanical ventilation.

PMID- 24034910
TI  - [A randomized controlled study of nasal intermittent positive pressure
      ventilation in the treatment of neonatal respiratory distress syndrome].
AB  - OBJECTIVE: To compare the clinical effects of nasal intermittent positive
      pressure ventilation (NIPPV) and nasal continuous positive airway pressure
      (NCPAP) in the treatment of neonatal respiratory distress syndrome. METHODS: A
      prospective, randomized, controlled, single-center study was performed on 67
      premature infants with NRDS between March 2011 and May 2012 and selected
      according to the inclusion and exclusion criteria. These premature infants were
      randomly assigned to receive NIPPV and NCPAP. Oxygenation index (OI), pH, PaCO2,
      duration of respiratory support, complications, success rate, hospital mortality,
      and incidence of bronchopulmonary dysplasia (BPD) were compared between the two
      groups. RESULTS: Sixty-two patients were finally enrolled in the study, including
      32 cases in the NIPPV group and 30 cases in the NCPAP group. After one hour of
      non-invasive ventilation, OI in the NIPPV group was higher than the NCPAP group
      (P<0.05), but there were no significant differences in pH and PaCO2 between the
      two groups (P>0.05 for both). A significantly lower proportion of infants needed
      mechanical ventilation via endotracheal tube (MVET) when they were treated
      initially with NIPPV than when they were treated initially with NCPAP (P<0.05).
      The NIPPV group had a significant higher success rate than the NCPAP group
      (P<0.05), but there was no significant difference in duration of respiratory
      support between the two groups (P>0.05). In addition, no significant differences
      in incidence of pneumothorax, hospital mortality and incidence of BPD were seen
      between the two groups (P>0.05 for all). CONCLUSIONS: Compared with NCPAP, NIPPV
      can significantly decrease the proportion of premature infants with NRDS in need
      of MVET. However, there is no evidence that NIPPV can significantly reduce
      hospital mortality and incidence of BPD in premature infants with NRDS.

PMID- 24034911
TI  - [Changes in plasma levels of atrial natriuretic peptide, endothelin-1 and von
      Willebrand factor among newborns with persistent pulmonary hypertension].
AB  - OBJECTIVE: To investigate the changes in plasma levels of atrial natriuretic
      peptide (ANP), endothelin-1 (ET-1) and von Willebrand factor (vWF), and their
      significance among newborns with persistent pulmonary hypertension (PPH).
      METHODS: Sixty-six newborns with PPH (case group) (mild: 26 cases; moderate: 21
      cases; severe: 19 cases), as well as 40 newborns without PPH (control group) who
      were hospitalized in the same period, were enrolled. The control group underwent
      echocardiography on admission. The case group underwent echocardiography before
      treatment (with refractory hypoxemia) and after 7 days of treatment for
      measurement of pulmonary artery systolic pressure (PASP). Meanwhile, plasma
      levels of ANP, ET-1 and vWF were measured using ELISA. RESULTS: Before treatment,
      the case group had significantly higher plasma levels of ANP, ET-1 and vWF than
      the control group (P<0.05), and these indices increased as PASP rose. After 7
      days of treatment, the children with mild or moderate PPH showed normal PASP, and
      their plasma levels of ANP, ET-1 and vWF were not significantly different from
      those of control group. The children with severe PPH had significant decreases in
      all indices, but they were significantly higher than those of the control group.
      Plasma levels of ANP, ET-1 and vWF were significantly positively correlated with
      PASP before and after treatment (P<0.01). CONCLUSIONS: Changes in plasma levels
      of ANP, ET-1 and vWF can reflect PASP in newborns with PPH during treatment.
      Dynamic monitoring of these indices can help to judge the severity of PPH and
      guide treatment.

PMID- 24034912
TI  - [Study on attention-deficit hyperactivity disorder in children based on resting
      state functional magnetic resonance imaging].
AB  - OBJECTIVE: To compare resting-state functional magnetic resonance imaging (fMRI)
      findings of children with attention-deficit hyperactivity disorder (ADHD) and
      normal children, and to investigate the possible mechanism of brain dysfunction
      in children with ADHD. METHODS: Resting-state fMRI was performed on 18 children
      who met the DSM-IV diagnostic criteria for ADHD (ADHD group) and 18 normal
      children (control group) matched for age, sex, IQ, degree of education and
      handedness. The two groups were compared in terms of amplitude of low frequency
      fluctuation (ALFF) and regional homogeneity (ReHo). RESULTS: Compared with the
      control group, the ADHD group had decreased ALFF in the bilateral posterior lobes
      of the cerebellum and the left side of the pons, increased ALFF in the right
      precentral gyrus, decreased ReHo in the left medial frontal gyrus, right superior
      frontal gyrus, and left precuneus, and increased ReHo in the left anterior lobe
      of the cerebellum, left caudate nucleus, right parahippocampal gyrus, left
      precentral gyrus, and right middle frontal gyrus. CONCLUSIONS: In resting state,
      children with ADHD have decreased brain activity in some regions, including the
      cerebellum and frontal cortex, compared with normal children, which supports the
      hypothesis of dysfunctional fronto-cerebellar circuits in ADHD.

PMID- 24034913
TI  - [Comorbidities and functional impairments in children with attention deficit
      hyperactivity disorder].
AB  - OBJECTIVE: To assess comorbidities and functional impairments in children with
      attention deficit hyperactivity disorder (ADHD), and to investigate their
      relationship with the core symptoms (attention deficit and hyperactivity) of
      ADHD. METHODS: A total of 319 children with suspected ADHD were included in the
      study. The Vanderbilt ADHD Parent Rating Scale (VADPRS) was completed by their
      parents. Diagnosis and classification were performed based on the Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition. Comorbidities and functional
      impairments were evaluated according to the VADPRS. Children with various types
      of ADHD were compared in terms of comorbidities and functional impairments, and
      their relationship with the core symptoms of ADHD was analyzed. RESULTS: Of the
      319 children, 196 were diagnosed with ADHD, including 84 cases of predominantly
      inattentive type (ADHD-I), 35 cases of predominantly hyperactive-impulsive type
      (ADHD-HI) and 77 cases of combined type (ADHD-C); 123 did not meet the diagnostic
      criteria for ADHD. At least one other psychiatric disorder (oppositional defiant
      disorder, conduct disorder or emotional disorder) was seen in 63.8% (125/196) of
      the children with ADHD, versus 37.4 % (46/123) of the children without ADHD
      (P<0.05). The incidence of oppositional defiant disorder and conduct disorder in
      the ADHD-C subgroup was significantly higher than in the ADHD-I subgroup
      (P<0.05). The sums of oppositional defiant disorder, conduct disorder and
      emotional disorder symptoms were weakly correlated with the sums of hyperactive
      impulsive and inattentive symptoms (P<0.01). Up to 89.8% of children with ADHD
      and 74.8% of children without ADHD showed functional impairments (P<0.05). The
      ADHD-C subgroup had a significantly higher overall incidence of functional
      impairments than the ADHD-I and ADHD-HI subgroups (P<0.05). The sum of
      inattentive symptoms was weakly correlated with the scores of learning ability,
      sibling relationship and participation in organized activities (P<0.01), and the
      sum of hyperactive-impulsive symptoms was weakly correlated with the score of
      sibling relationship (P<0.01). CONCLUSIONS: The incidence of comorbidities and
      functional impairments among children with ADHD is high, especially in those with
      ADHD-C. The severity of core symptoms in children with ADHD can influence the
      occurrence of comorbidities and functional impairments. The incidence of
      psychiatric disorders and functional impairments is also high in children with
      suspected ADHD who do not meet the diagnostic criteria for ADHD, so attention
      also needs to be paid to interventions among these children.

PMID- 24034914
TI  - [Clinical features and comorbidities of Asperger syndrome in children].
AB  - OBJECTIVE: To investigate and summarize the clinical features and comorbidities
      of Asperger syndrome (AS) in children and to provide a theoretical basis for
      improving the understanding and diagnosis of AS. METHODS: Inquiry of medical
      history, physical examination, behavioral observation, psychiatric examination,
      questionnaire survey, and the Wechsler Intelligence Scale were used to summarize
      and analyse the clinical data of 95 children with AS, including chief complaint,
      symptoms, perinatal and familial conditions, family genetic history, and common
      comorbidities. RESULTS: AS was more common in male children, with hyperactivity,
      inattention, and social withdrawal as frequent chief complaints. The main
      clinical manifestations included poor communication skills (95%), restricted
      interest (82%), repetitive and stereotyped patterns of behavior (77%), semantic
      comprehension deficit (74%), and indiscipline (68%). Verbal IQ was higher than
      performance IQ in most patients. The comorbidities of AS included attention
      deficit hyperactivity disorder (ADHD) (39%), emotional disorder (18%), and
      schizophrenia (2%); emotional disorder was more common in patients aged 13-16
      years, while ADHD was more common in patients aged 7-16 years. Among these
      patients, 61% had fathers with introverted personality, 43% had mothers with
      introverted personality, and 19% had a family history of mental illness.
      CONCLUSIONS: AS has specific clinical manifestations. It is essential to know
      more about the clinical features and comorbidities of AS, which is helpful for
      early identification and diagnosis of AS.

PMID- 24034915
TI  - [A clinical study of drug-related toxicities of CCLG-ALL 08 protocol for
      childhood acute lymphoblastic leukemia].
AB  - OBJECTIVE: The Chinese Children's Leukemia Group (CCLG)-acute lymphoblastic
      leukemia (ALL) 08 protocol for childhood ALL was established in 2008. This study
      aims to evaluate the drug-related toxicities of CCLG-ALL 08 protocol in the
      treatment of childhood ALL. METHODS: A total of 114 children with newly diagnosed
      ALL were treated with the CCLG-ALL 08 protocol. The protocol was divided into
      five phases: remission induction (VDLD), early reinforcement (CAM), consolidation
      therapy, delayed reinforcement (DIa & DIb) and maintenance treatment. Drug
      related toxicities in each phase were evaluated according to the Common
      Terminology Criteria for Adverse Events version 4.0. RESULTS: Toxicities were
      more frequent in phase VDLD than other treatment phases, including hepatotoxicity
      (87.7%), dental ulcer (20.2%), hyperglycemia (20.2%), prolonged activated partial
      thromboplastin time (21.1%) and decreased fibrinogen (34.2%), with the incidence
      rates of severe adverse events at 7%, 0, 1.3%, 0.8% and 2.7% respectively. The
      incidence of allergic reaction to L-ASP was significantly higher in phase DIa
      than in phase VDLD (28.0% vs 7.9%; P<0.01), and there were no longer any allergic
      reactions in 15 patients who received continuing treatment with pegaspargase
      instead. There was no severe arrhythmia, myocardial ischemia, decreased left
      ventricular function, osteonecrosis, myopathy, organ failure or treatment-related
      mortality. CONCLUSIONS: The drug-related toxicities of CCLG-ALL 08 protocol are
      common in phase VDLD, but they are mild and reversible. There is no treatment
      related mortality. The CCLG-ALL 08 protocol for childhood ALL is safe.

PMID- 24034916
TI  - [The abnormal expression of IKZF1 encoded protein-IKAROS in B-ALL children].
AB  - OBJECTIVE: To analyze the isoforms of IKAROS in the bone marrow samples from
      children with acute B-lineage lymphoblastic leukemia (B-ALL) and to investigate
      the relationship between frequency of dominant-negative (DN) IKAROS isoforms and
      prognosis of B-ALL, and to preliminarily study the relevant mechanism. METHODS: A
      total of 137 children with newly diagnosed B-ALL, who sequentially entered the
      Department of Hematology and Oncology, Shanghai Children's Medical Center between
      January 2005 and September 2010, were included in the study. Nest-PCR, Sanger
      sequencing, and TA cloning were used to analyze the expression of IKAROS isoforms
      in these children. The relationship between frequency of DN IKAROS isoforms and
      prognosis of B-ALL was investigated. RESULTS: Of the 137 children with newly
      diagnosed B-ALL, 16 had expression of IK6, 14 had expression of IK4, and 2 had
      expression of IK7. There was significant difference in 2.5-year event-free
      survival between the cohorts of DN IKAROS and non-DN IKAROS (P=0.01). Analysis of
      the 10 paired of diagnosis/relapse samples from 10 patients with recurrence
      showed that 8 of 10 paired diagnosis and relapse samples had inconsistent
      expression of IKAROS isoforms. The rate of IK6 expression in relapse samples from
      21 relapse ALL patients was significantly higher than in the 137 children with
      newly diagnosed ALL (62% vs 12%, P<0.01). CONCLUSIONS: Expression of DN IKAROS
      isoforms can be a poor prognostic factor in B-ALL and is closely associated with
      recurrence of B-ALL.

PMID- 24034917
TI  - [Application of HCMV DNA detection in infants' blood, urine and mothers' breast
      milk in the diagnosis of HCMV infection among infants].
AB  - OBJECTIVE: To quantify human cytomegalovirus (HCMV) DNA in the blood and urine of
      infants of different ages with suspected HCMV infection, and in the breast milk
      of their mothers, and to evaluate the significance of HCMV DNA detection in the
      three specimen types in the diagnosis of HCMV infection among infants of
      different ages. METHODS: A total of 170 infants with suspected HCMV infection
      were divided into groups A (<28 days; n=43) and B (28 days to 5 months; n=127)
      according to their ages. Blood and urine were collected from the infants, and
      breast milk was collected from their mothers. The specimens were examined by
      fluorescence quantitative PCR for detection of HCMV DNA. RESULTS: In group A,
      HCMV DNA detection rates in blood, urine and breast milk were 65.1%, 18.6% and
      93.0% respectively. In group B, HCMV DNA detection rates in blood, urine and
      breast milk were 64.6%, 92.9% and 72.4% respectively. HCMV DNA detection rate in
      urine in group B was significantly higher than in group A (P<0.01), however, HCMV
      DNA detection rate in mothers' breast milk in group B was significantly lower
      than in group A (P<0.01). Among the 82 infants with positive results for blood
      and urine, the copy number of HCMV DNA in urine was significantly higher than
      that in blood. CONCLUSIONS: HCMV DNA detection rates in urine and breast milk are
      different among infants of different ages, so use of suitable specimens according
      to age is of great significance for improving detection rate.

PMID- 24034918
TI  - [Relationship between G6PD deficiency and hand-foot-mouth disease induced by
      enterovirus 71].
AB  - OBJECTIVE: To study the influence of glucose-6-phosphate dehydrogenase (G6PD)
      deficiency on hand-foot-mouth disease (HFMD) induced by enterovirus 71 (EV71) ,
      and possible mechanisms. METHODS: A total of 220 boys with HFMD induced by EV71
      were classified into two groups based on disease severity: mild/moderate (n=145)
      and severe HFMD groups (n=75), and 132 healthy boys were selected as the control
      group. The activity of G6PD and levels of reduced glutathione (GSH) and
      malonaldehyde (MDA) in blood were measured using the automatic biochemical
      analyzer. RESULTS: The percentage of G6PD deficiency cases in the severe HFMD
      group was significantly higher than in the control group (P<0.0125). In the
      severe HFMD group, the durations of fever, mental abnormality, limb trembling and
      hospital stay were significantly longer in children with G6PD deficiency than in
      those with normal G6PD activity (P<0.05). In the acute and recovery stages,
      patients in the mild/moderate and severe HFMD groups had significantly lower GSH
      levels and G6PD activity and significantly higher MDA levels compared with those
      in the control group (P<0.05). In the acute stage, children in the mild/moderate
      and severe HFMD groups with G6PD deficiency had significantly lower GSH levels
      and significantly higher MDA levels compared with those with normal G6PD activity
      (P<0.01). In the acute and recovery stages, GSH level in children with HFMD was
      positively correlated with G6PD activity (r=0.61, P<0.01; r=0.58, P<0.01), and in
      the acute stage, MDA level was negatively correlated with G6PD activity (r=-0.29,
      P<0.01). CONCLUSIONS: G6PD deficiency is probably a predisposing factor for HFMD
      induced by EV71 and may aggravate the patient's condition. Its mechanism might be
      related to oxidative stress.

PMID- 24034919
TI  - [Effects of ursodeoxycholic acid on mRNA expression of MDR3 and FXR in infants
      with cholestatic hepatitis].
AB  - OBJECTIVE: To analyze the effects of ursodeoxycholic acid (UDCA) on the mRNA
      expression of multidrug resistance protein 3 (MDR3) and farnesoid X receptor
      (FXR) in infants with cholestatic hepatitis. METHODS: Twenty-eight infants who
      were diagnosed with cholestatic hepatitis between July 2008 and July 2010 were
      included in the study. These patients received treatment with UDCA. The mRNA
      expression levels of MDR3 and FXR were measured by real-time quantitative RT-PCR
      with SYBR Green I, before and after treatment with UDCA. RESULTS: After treatment
      with UDCA, the infants with cholestatic hepatitis had significantly decreased
      serum levels of total bilirubin, direct bilirubin, alanine aminotransferase, and
      gamma-glutamyltransferase (P<0.05) and significantly increased mRNA expression of
      MDR3 (P<0.05). No significant change in mRNA expression of FXR was observed,
      however (P>0.05). CONCLUSIONS: UDCA improves liver function indices in infants
      with cholestatic hepatitis, which may be related to up-regulated mRNA expression
      of MDR3.

PMID- 24034920
TI  - [Diagnostic values of bronchoscopy and multi-slice spiral CT for congenital
      dysplasia of the respiratory system in infants: a comparative study].
AB  - OBJECTIVE: To investigate and compare the diagnostic values of bronchoscopy and
      multi-slice spiral computed tomography (CT) for congenital dysplasia of the
      respiratory system in infants. METHODS: Analysis was performed on the clinical
      data, bronchoscopic findings and multi-slice spiral CT findings of 319 infants
      (<=1 years old) who underwent bronchoscopy and/or multi-slice spiral CT and were
      diagnosed with congenital dysplasia of the respiratory system. RESULTS: A total
      of 476 cases of congenital dysplasia of the respiratory system were found in the
      319 infants, including primary dysplasia of the respiratory system (392 cases)
      and compressive dysplasia of the respiratory system (84 cases). Of the 392 cases
      of primary dysplasia of the respiratory system, 225 (57.4%) were diagnosed by
      bronchoscopy versus 167 (42.6%) by multi-slice spiral CT. There were significant
      differences in etiological diagnosis between bronchoscopy and multi-slice spiral
      CT in infants with congenital dysplasia of the respiratory system (P<0.05). All
      76 cases of primary dysplasia of the respiratory system caused by
      tracheobronchomalacia were diagnosed by bronchoscopy and all 17 cases of primary
      dysplasia of the respiratory system caused by lung tissue dysplasia were
      diagnosed by multi-slice spiral CT. Of the 84 cases of compressive dysplasia of
      the respiratory system, 74 cases were diagnosed by multi-slice spiral CT and only
      10 cases were diagnosed by bronchoscopy. CONCLUSIONS: Compared with multi-slice
      spiral CT, bronchoscopy can detect primary dysplasia of the respiratory system
      more directly. Bronchoscopy is valuable in the confirmed diagnosis of
      tracheobronchomalacia. Multi-slice spiral CT has a higher diagnostic value for
      lung tissue dysplasia than bronchoscopy.

PMID- 24034921
TI  - [1,25-(OH)2D3 inhibits lipopolysaccharide-induced expression of interleukin-13
      and interleukin-17 in cord blood CD4+T cells].
AB  - OBJECTIVE: To study the effect of 1,25-(OH)2D3 on lipopolysaccharide (LPS)
      induced expression of interleukin-13 (IL-13) and interleukin-17 (IL-17) in cord
      blood CD4(+)T cells, providing theoretical basis for clinical reasonable
      application of vitamin D and prevention of asthma and allergic diseases. METHODS:
      Mononuclear cells (MNCs) were isolated from umbilical cord blood (50 mL) of 12
      normal eutocia term newborns by gravity centrifugation. CD4(+)T cells were
      isolated using magnetic beads, which was cultured with following three kinds of
      stimulus for 72 hours: natural state (blank group), LPS (10 MUg/mL)stimulation
      alone and LPS(10 MUg/mL)+1,25-(OH)2D3 (10(-8) mmol/L)stimulation. Levels of IL-13
      and IL-17 in the culture supernatant and mRNA expressions in cord blood CD4(+)T
      cells were detected using ELISA and real Time-PCR respectively. RESULTS: Compared
      with the blank group, levels of IL-13 and IL-17 in the culture supernatant and
      mRNA expression of IL-13 and IL-17 in the cord blood CD4(+)T cells increased in
      the LPS stimulation alone group (P<0.01). When co-stimulation of 1,25-(OH)2D3
      with LPS, levels of IL-13 and IL-17 in the culture supernatant and mRNA
      expression of IL-13 and IL-17 in the cord blood CD4(+)T cells decreased compared
      with LPS-stimulated alone group (P<0.05), but remained higher than the blank
      group (P<0.01). CONCLUSIONS: LPS can promote expression of IL-13 and IL-17 in
      cord blood CD4(+)T cells. 1,25-(OH)2D3 inhibits the expression of IL-13 and IL
      17, suggesting that vitamin D intake may provide protective effects in the
      development of atopy-predisposing immune responses in early life.

PMID- 24034922
TI  - [Association of single nucleotide polymorphism in TGFBR2 gene with Kawasaki
      disease and coronary artery lesions].
AB  - OBJECTIVE: To examine the single nucleotide polymorphism (SNP) (rs1495592) in
      transforming growth factor-beta receptor 2 (TGFBR2) gene in children, and to
      investigate its association with Kawasaki disease (KD) and coronary artery
      lesions (CALs). METHODS: Thirty-five KD patients, 14 of whom had CALs (CAL
      subgroup), were selected as the case group, and 25 healthy age-matched children
      were selected as the control group. The SNP (rs1495592) in TGFBR2 gene was
      studied by gene sequencing. The association of SNP (rs1495592) with KD and (CALs)
      was analyzed based on the sequencing results. RESULTS: There were no significant
      differences in genotype frequency distribution (chi(2)=0.566, P=0.452) and allele
      frequency distribution (chi(2)=0.216, P=0.642) between the two groups. Genotypes
      in the CAL subgroup included CC (21.4%) and CT+TT (78.6%), while genotypes in the
      non-CAL subgroup included CC (61.9%) and CT+TT (38.1%). There was significant
      difference in genotype frequency distribution between the two groups
      (chi(2)=5.546, P=0.019), but without significant difference in allele frequency
      distribution (chi(2)=3.673, P=0.055). CONCLUSIONS: The SNP (rs1495592) in TGFBR2
      gene may not be associated with development of KD in children, but it is
      associated with CALs in children with KD.

PMID- 24034923
TI  - [Clinical significance of changes in T wave and ST segment amplitudes on
      electrocardiogram from supine to standing position among children with
      unexplained chest tightness or pain in resting stage].
AB  - OBJECTIVE: To investigate the clinical significance of changes in T wave and ST
      segment amplitudes on electrocardiogram (ECG) from supine to standing position in
      children with unexplained chest tightness or pain in resting stage. METHODS: A
      total of 122 6-14-year-old children with a chief complaint of unexplained chest
      tightness or pain (resting stage) underwent head-up tilt test (HUTT). According
      to HUTT results, these children were divided into HUTT-positive (n=61) and HUTT
      negative groups (n=61). They underwent 12-lead ECG in the supine and standing
      positions, and heart rate and T wave and ST segment amplitudes in II, III, aVF
      and V5 leads were measured. RESULTS: In the HUTT-negative group, heart rates were
      significantly higher in the standing position than in the supine position
      (P<0.05), T wave amplitudes in II, III, aVF, and V5 leads were significantly
      lower in the standing position than in the supine position (P<0.05), and ST
      segment amplitudes in II, aVF and V5 leads were significantly higher in the
      standing position than in the supine position (P<0.05). In the HUTT-positive
      group, heart rates were significantly higher in the standing position than in the
      supine position (P<0.05), T wave amplitudes in II, III, aVF and V5 leads were
      significantly lower in the standing position than in the supine position
      (P<0.05), and ST segment amplitude in V5 lead was significantly higher in the
      standing position than in the supine position (P<0.05). There were no significant
      differences between the two groups with respect to ST segment amplitude and T
      wave amplitude in II, III and aVF leads of the supine or standing position
      (P>0.05). Compared with the HUTT-negative group, the HUTT-positive group had
      significantly greater T wave amplitude differences in II, III, aVF and V5 leads,
      and heart rate difference from supine to standing position (P<0.05). CONCLUSIONS:
      Among the children with unexplained chest tightness or pain in resting stage, T
      wave amplitude differences in II, III, aVF and V5 leads and heart rate difference
      from supine to standing position are greater in the HUTT-positive group than in
      the HUTT-negative group. This suggests that the changes in T wave amplitude on
      ECG from supine to standing position can indicate autonomic nervous system
      dysfunction.

PMID- 24034924
TI  - [Effects of umbilical cord blood monocytes transplantation on EPO protein and
      oligodendrocyte progenitors in neonatal rats with hypoxic-ischemic brain damage].
AB  - OBJECTIVE: To study the effects of umbilical cord blood monocytes (UCBMC)
      transplantation on erythropoietin (EPO) protein and oligodendrocyte progenitor
      cells in hypoxia-ischemia (HI) neonatal rats. METHODS: Forty seven-day-old
      Sprague-Dawley rats were randomly divided into normal control (N), HI, UCBMC and
      HI+UCBMC groups (n=10 each). Hypoxic-ischemic brain damage (HIBD) model was
      prepared according to the Rice method. Twenty-four hours after hypoxia, the N and
      HI groups were injected with 2 MUL phosphate buffered saline (PBS), and the UCBMC
      and HI+UCBMC groups were injected with 3*10(6) UCBMC via the lateral ventricle.
      EPO protein and oligodendrocyte progenitor cells in the subventricular zone of
      the injured brain were observed by EPO/DAPI and NG2/DAPI immunofluorescence
      double staining, and their correlation was analyzed. RESULTS: Seven days after
      transplantation, there were more NG2(+)DAPI(+) and EPO(+)DAPI(+) cells in the
      HI+UCBMC group than in the UCBMC (P<0.05), N and HI groups (P<0.01). More
      NG2(+)DAPI(+) and EPO(+)DAPI(+) cells were observed in the UCBMC group compared
      with the N and HI groups (P<0.01). There were more NG2(+)DAPI(+) cells in the N
      group than in the HI group (P<0.01). The number of NG2(+)DAPI(+) cells was
      correlated with the number of EPO(+)DAPI(+) cells in the HI+UCBMC group (r=0.898,
      beta=1.4604, P<0.01). CONCLUSIONS: UCBMC can promote expression of
      oligodendrocyte progenitor cells, which is correlated with an increase in EPO
      protein and thus repairs brain white matter damage in neonatal rats with HIBD.

PMID- 24034925
TI  - [Characteristics of ictal and interictal ambulatory electroencephalogram in 150
      children with infantile spasms].

PMID- 24034926
TI  - [Allogeneic hematopoietic stem cell transplantation for the treatment of Niemann
      Pick disease type A: a case report].

PMID- 24034927
TI  - [Clinical analysis of 7 cases of neonatal hematogenous osteomyelitis].

PMID- 24034928
TI  - [Thioguanine treatment-related sinusoidal obstruction syndrome in 2 children].

PMID- 24034929
TI  - [CT and MR imaging features in 4 children with cerebral paragonimiasis].

PMID- 24034930
TI  - [Atrial flutter in a neonate with atrial septal aneurysm].

PMID- 24034931
TI  - [Latest update on immunotherapy of Epstein-Barr virus-associated post
      transplantation lymphoproliferative disease].
AB  - Epstein-Barr virus (EBV)-associated post-transplantation lymphoproliferative
      disease (EBV-PTLD) is a potentially life-threatening complication after
      hematopoietic stem cell transplantation or solid organ transplantation. In the
      last decade, the survival of patients with EBV-PTLD has been significantly
      improved by immunotherapeutic interventions among high-risk patients. The
      immunotherapeutic interventions for EBV-PTLD include reduction in
      immunosuppression, CD20 monoclonal antibodies (rituximab) as monotherapy or in
      combination with chemotherapy, and adoptive immunotherapy with EBV-specific T
      cells. This paper reviews the latest update on the high-risk factors, clinical
      manifestations and immunotherapy of EBV-PTLD. 

PMID- 24034932
TI  - [Research progress in cytokines and signaling pathways for promoting pulmonary
      angiogenesis and vascular development].
AB  - With the advances in pre- and post-natal medical care, the incidence of
      bronchopulmonary dysplasia (BPD) is on the rise, while its pathogenesis remains
      not clear. New BPD theory shows that the core pathogenesis of BPD is simple
      alveolar structure and pulmonary microvascular abnormalities that eventually lead
      to reduced pulmonary gas exchange, so the research on pulmonary microvascular
      development was gradually taken seriously. Pulmonary angiogenesis and vascular
      development require the participation of various cytokines and signaling
      pathways, the most important of which include VEGF/VEGFR pathway, Ang/Tie
      pathway, Ephrins/Eph pathway, and Notch/Jagged1 pathway. These cytokines and
      signaling pathways play important roles in pulmonary vascular development. 

PMID- 24034933
TI  - Induction of Toll-like receptor 4 signaling in avian macrophages inhibits
      infectious laryngotracheitis virus replication in a nitric oxide dependent way.
AB  - LPS is one of the pathogen associated molecular patterns that activates Toll-like
      receptor 4 (TLR4) signaling pathway eliciting antiviral host responses in mammals
      although information on such responses in avian species is scarce. Our objectives
      were to characterize the LPS induced innate responses particularly the expression
      of LPS receptors (TLR4, CD14) in avian macrophages and observe whether TLR4
      mediated induction of NO can elicit antiviral response against infectious
      laryngotracheitis virus (ILTV) replication. We found that LPS was capable of
      inducing the expression of TLR4, CD14 and NO production but not the type 1
      interferons in an avian macrophage cell line, MQ-NCSU. We also showed that TLR4
      mediated NO production can lead to antiviral response against ILTV replication
      when MQ-NCSU cells were treated with LPS and the resultant supernatant was then
      transferred to ILTV replicating cells to assess antiviral activity. Antiviral
      activity of NO was blocked by a selective inhibitor, S-methylisothiourea sulfate
      that inhibits inducible NO synthase. This observation confirms that the antiviral
      activity is positively correlated with NO production. The data show that LPS can
      be a potential innate immune stimulant that can be used against ILTV infection in
      chickens that require further evaluation in vivo.

PMID- 24034934
TI  - Increasing the ex vivo antigen-specific IFN-gamma production in subpopulations of
      T cells and NKp46+ cells by anti-CD28, anti-CD49d and recombinant IL-12
      costimulation in cattle vaccinated with recombinant proteins from Mycobacterium
      avium subspecies paratuberculosis.
AB  - T cells, which encounter specific antigen (Ag), require additional signals to
      mount a functional immune response. Here, we demonstrate activation of signal 2,
      by anti-CD28 mAb (aCD28) and other costimulatory molecules (aCD49d, aCD5), and
      signal 3, by recombinant IL-12, enhance Ag-specific IFN-gamma secretion by CD4,
      CD8, gammadelta T cells and NK cells. Age matched male jersey calves,
      experimentally infected with Mycobacterium avium subsp. paratuberculosis (MAP),
      were vaccinated with a cocktail of recombinant MAP proteins or left unvaccinated.
      Vaccine induced ex vivo recall responses were measured through Ag-specific IFN
      gamma production by ELISA and flow cytometry. There was a significant increase in
      production of IFN-gamma by T cell subsets or NKp46+ cells cultured in the
      presence of Ag and aCD28/aCD49d. The increase was accompanied by an increase in
      the integrated median fluorescence intensity (iMFI) of activated T cells.
      Addition of rIL-12 induced a significant additive effect leading to a maximum
      increase in responder frequency of Ag-specific T cell subsets or NKp46+ cells
      with a heavy bias toward IFN-gamma production by CD4 T cells. We provide the
      first description of using aCD28/aCD49d costimulation to potentiate an Ag
      specific increase in the production of IFN-gamma in bovine immunology. The study
      also shows the degree of signaling in T cells is regulated by the costimulatory
      environment. 

PMID- 24034935
TI  - DNA fragmentation of human sperm can be detected by ligation-mediated real-time
      polymerase chain reaction.
AB  - OBJECTIVE: To determine whether ligation-mediated real-time polymerase chain
      reaction (LM-RT-PCR), which combines LM-PCR, and RT-PCR, can detect sperm DNA
      fragmentation (DF) in human semen samples. DESIGN: Three-way comparison of
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), sperm
      chromatin dispersion (SCD), and LM-RT-PCR for detecting sperm DNA fragmentation.
      SETTING: University hospital-based research laboratory. PATIENT(S): Twenty-five
      men presenting at an infertility clinic. INTERVENTION(S): Basic analysis of sperm
      concentration, motility, vitality, and morphology, with each semen sample equally
      divided into three aliquots that were evaluated for fragmentation using TUNEL,
      SCD, and LM-RT-PCR assays. MAIN OUTCOME MEASURE(S): In TUNEL and SCD assays,
      counts of the number of sperm with tetramethylrhodamine (TMR) red signals or no
      halo; in LM-RT-PCR results, evaluation of the threshold cycles (Ct) and relative
      fluorescence unit (RFU) values. RESULT(S): The median percentage of sperm with
      positive results for fragmentation in the TUNEL and SCD assays were 20.5% and
      20.7%, respectively. To compare the accuracy of the TUNEL, SCD, and LM-RT-PCR
      assays, we divided the semen samples into two groups according to the TUNEL
      results: low and high percentage of sperm fragmentation. In the LM-RT-PCR
      results, the values of the cycles of threshold (Ct) and relative fluorescence
      unit (RFU) statistically significantly differed between the low and high
      percentage of sperm fragmentation groups. Comparisons among the TUNEL, SCD, and
      LM-RT-PCR assays revealed that the correlation patterns according to DNA
      fragmentation were similar in both the groups with high and low percentage of DNA
      fragmentation. Our morphologic analysis indicated that the fragmentation of sperm
      DNA did not appear to influence sperm morphology. CONCLUSION(S): These results
      indicate that the LM-RT-PCR technique is another useful tool for detecting DNA
      fragmentation, a parameter of sperm quality in human semen alone or combined with
      TUNEL or SCD assays.

PMID- 24034936
TI  - Chronic exposure to a low concentration of bisphenol A during follicle culture
      affects the epigenetic status of germinal vesicles and metaphase II oocytes.
AB  - OBJECTIVE: To determine whether exposure to low concentrations of the endocrine
      disrupting chemical bisphenol A (BPA) during follicle culture and oocyte growth
      alters the methylation status of differentially methylated regions (DMRs) of
      imprinted genes and histone posttranslational modification patterns in mammalian
      oocytes. DESIGN: Comparative and control study. SETTING: Experimental laboratory.
      ANIMAL(S): C57/Bl6JxCBA/Ca mice. INTERVENTION(S): Exposure of oocytes to 3 nM or
      300 nM BPA during follicle culture from preantral to antral stage. MAIN OUTCOME
      MEASURE(S): Methylation status of DMRs of maternally imprinted (Snrpn, Igf2r, and
      Mest) and paternally imprinted gene(s) (H19) in mouse germinal vesicle oocytes;
      trimethylation of histone H3K9, acetylation of histone H4K12, and distance
      between centromeres of sister chromatids in metaphase II oocytes. RESULT(S):
      Exposure to 3 nM BPA was associated with slightly accelerated follicle
      development, statistically significant increases in allele methylation errors in
      DMRs of maternally imprinted genes, and statistically significant decreases in
      histone H3K9 trimethylation and interkinetochore distance. CONCLUSION(S): The
      disturbances in oocyte genomic imprinting and modification of posttranslational
      histone and centromere architecture provide the first link between low BPA
      exposures and induction of epigenetic changes that may contribute to chromosome
      congression failures and meiotic errors, and to altered gene expression that
      might affect health of the offspring.

PMID- 24034937
TI  - Semen cryopreservation for men banking for oligospermia, cancers, and other
      pathologies: prediction of post-thaw outcome using basal semen quality.
AB  - OBJECTIVE: To evaluate post-thawing sperm parameters in a large series of men
      cryopreserving for different cancers and oligospermia. DESIGN: Retrospective
      observational study. SETTING: Semen cryopreservation laboratory. PATIENT(S): Six
      hundred twenty-three patients undergoing semen cryopreservation for cancer or
      oligospermia who discontinued banking. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Postcryopreservation sperm motility and viability. RESULT(S): In
      oligospermic men, recovery of motile sperm after cryopreservation was possible in
      only a few out of the 219 samples cryopreserved for this problem. Similarly,
      independent of the reason for which cryopreservation was required, if one basal
      semen parameter fell below the 5th percentile of the World Health Organization
      reference values, recovery of motile and viable spermatozoa after thawing was
      low. Among samples cryopreserved for cancer, those with testicular cancer showed
      the lowest basal semen quality and recovery after thawing. In cases of
      hematological cancers or other types of cancers, motility recovery was similar to
      that of non-cancer-related samples. Receiver operating characteristic analyses
      demonstrate that basal progressive and total motility predict the recovery rate
      of motile sperm after thawing with high accuracy, sensibility and specificity.
      CONCLUSION(S): Our study demonstrates the ability of prefreeze semen parameters
      to predict cryosurvival in terms of sensitivity and precision. Using this
      information, the clinician could perform appropriate counseling about the future
      possibilities of fertility for the patient.

PMID- 24034938
TI  - Effects of sleep deprivation during pregnancy on the reproductive capability of
      the offspring.
AB  - OBJECTIVE: To investigate the effects of sleep deprivation during pregnancy on
      the reproductive capability of the offspring. DESIGN: Using a sleep loss model or
      control home-cage group (male and females rats) to evaluate sexual behavior and
      hormonal profile in males and females F1 offspring. SETTING: Laboratory.
      ANIMALS(S): First experiment: Pregnant females were exposed to sleep restriction
      (SR) protocol and the F1 generation was evaluated. Second experiment: male rats
      were submitted to SR or paradoxical sleep deprivation (PSD) protocol and the F1
      generation was evaluated. INTERVENTION(S): Male and female rats were subjected to
      sleep restriction (SR) for 21 days or paradoxal sleep-deprived (PSD) for 96
      hours. MAIN OUTCOME MEASURE(S): Sexual behavior and hormonal levels during the
      adult phase were analyzed in F1 offspring of female and male rats submitted to
      sleep loss. RESULT(S): F1 male offspring of SR females had lower motivation for
      sex and reduced progesterone concentrations. In contrast, F1 female offspring
      displayed significantly enhanced proceptivity compared with control offspring. F1
      female offspring also demonstrated hypersexuality by mounting the males in the
      absence of any significant hormonal alterations. F1 male offspring of SR or
      paradoxically sleep-deprived (PSD) males presented a decline in the sexual
      response, accompanied by a reduction in testosterone concentrations. Proceptivity
      was significantly increased among F1 female offspring of PSD and SR males
      compared with control offspring. CONCLUSION(S): SR in progenitors may alter
      sexual behavior of the F1 offspring in adulthood. These findings reveal far
      reaching consequences of sleep deprivation, and suggest that parental sleep
      influences the reproductive capability of subsequent generations.

PMID- 24034939
TI  - Diminished effect of maternal age on implantation after preimplantation genetic
      diagnosis with array comparative genomic hybridization.
AB  - OBJECTIVE: To assess the relationship between maternal age, chromosome
      abnormality, implantation, and pregnancy loss. DESIGN: Multicenter retrospective
      study. SETTING: IVF centers in the United States. PATIENT(S): IVF patients
      undergoing chromosome screening. INTERVENTION(S): Embryo biopsy on day 3 or day
      5/6 with preimplantation genetic diagnosis (PGD) by array comparative genomic
      hybridization. MAIN OUTCOME MEASURE(S): Aneuploidy, implantation, pregnancy, and
      loss rates. RESULT(S): Aneuploidy rates increased with maternal age from 53% to
      93% for day 3 biopsies and from 32% to 85% for blastocyst biopsies. Implantation
      rates for euploid embryos for ages <35-42 years did not decrease after PGD:
      ranges 44%-32% for day 3 and 51%-40% for blastocyst. Ongoing pregnancy rates per
      transfer did not decrease for maternal ages <42 years after PGD with day 3 biopsy
      (48.5%-38.1%) or blastocyst biopsy (64.4%-54.5%). Patients >42 years old had
      implantation rates of 23.3% (day 3), 27.7% (day 5/6), and the pregnancy rate with
      day 3 biopsy was 9.3% and with day 5 biopsy 10.3%. CONCLUSION(S): Selective
      transfer of euploid embryos showed that implantation and pregnancy rates were not
      significantly different between reproductively younger and older patients up to
      age 42 years. Some patients who start an IVF cycle planning to have chromosome
      screening do not have euploid embryos available for transfer, a situation that
      increases with advancing maternal age. Mounting data suggests that the dramatic
      decline in IVF treatment success rates with female age is primarily caused by
      aneuploidy.

PMID- 24034941
TI  - A new menstrual pictogram for use with feminine products that contain
      superabsorbent polymers.
AB  - OBJECTIVE: To determine whether the menstrual pictogram (the superabsorbent
      polymer-c or SAP-c version) can reliably estimate blood and total menstrual fluid
      volumes on prestained Always Ultra slim feminine towels (Proctor & Gamble) that
      contain superabsorbent polymers. DESIGN: Randomized blinded study using simulated
      menstrual fluid (SMF: 50% blood, 50% saline mixture). SETTING: Gynecology
      research clinic. PATIENT(S): 12 premenopausal women with regular menstrual cycles
      who had not previously used a graphical method to assess menstrual loss.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Assignment of 135 prestained
      towels containing known volumes of 0.5-25.0 mL of SMF to five pictorial icons of
      the menstrual pictogram, and correlation of pictogram scores to blood recovered
      from towels by the alkaline hematin method and total fluid applied to towels by
      measurement of soiled towel weight. RESULT(S): There was a high level of
      agreement between individual scores. For 112 (83%) of 135 towels, the
      participants' readings either completely concurred or differed by only a single
      icon. There was a statistically significant correlation between the volume of
      blood applied (SMF/2) and that recovered by alkaline hematin, and volume of fluid
      applied and soiled towel weight. CONCLUSION(S): The menstrual pictogram (SAP-c
      version) is a potential diagnostic tool for heavy menstrual bleeding and would be
      suitable for testing in a clinical trial.

PMID- 24034942
TI  - Prevalence of and risk factors for domestic violence among pregnant women in
      Nigeria.

PMID- 24034940
TI  - Polycystic ovary syndrome and nonalcoholic fatty liver in obese adolescents:
      association with metabolic risk profile.
AB  - OBJECTIVE: To investigate the relationship between liver fat and in vivo insulin
      sensitivity, body composition, abdominal adiposity, and lipid metabolism in obese
      adolescent girls with polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional
      case-control study. SETTING: Research center. PATIENT(S): Thirty Tanner stage V
      obese girls with PCOS. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Liver fat,
      abdominal adiposity, in vivo insulin-stimulated glucose disposal, whole-body
      lipolysis, fat oxidation, lipoprotein particle size and concentration, and liver
      enzymes (alanine aminotransferase and aspartate aminotransferase). Fatty liver
      index <1 is indicative of fatty liver. RESULT(S): Fatty liver was present in 6.7%
      of the individuals (6.7%). Levels of alanine aminotransferase and aspartate
      aminotransferase were not different between those with fatty liver vs. without.
      Fatty liver index was associated with age (r = -0.53), body mass index (r = 
      0.41), total (r = -0.43) and subcutaneous (r = -0.41) abdominal adiposity,
      insulin-stimulated glucose disposal (r = 0.36), and small, medium small, and very
      small low-density lipoprotein concentrations (r >= -0.43). In a multiple
      regression analysis, age, total T, race, and insulin-stimulated glucose disposal
      explained 43% of the variance (R(2) = 0.43) in fatty liver index, with age (R(2)
      = 0.28) and total T (R(2) = 0.11) being independent contributors. CONCLUSION(S):
      Liver fat is associated with increasing age, even in the narrow adolescent age
      range, increasing abdominal adiposity, worsening insulin sensitivity, and
      dyslipoproteinemia in obese adolescent girls with PCOS. Targeting these
      abnormalities early in the course of PCOS may halt future nonalcoholic fatty
      liver disease in adulthood.

PMID- 24034943
TI  - Comparison of microbial diversity determined with the same variable tag sequence
      extracted from two different PCR amplicons.
AB  - BACKGROUND: Deep sequencing of the variable region of 16S rRNA genes has become
      the predominant tool for studying microbial ecology. As sequencing datasets have
      accumulated, meta-analysis of sequences obtained with different variable 16S rRNA
      gene targets and by different sequencing methods has become an intriguing
      prospect that remains to be evaluated experimentally. RESULTS: We amplified a
      group of fecal samples using both V4F-V6R and V6F-V6R primer sets, excised the
      same V6 fragment from the two sets of Illumina sequencing data, and compared the
      resulting data in terms of the alpha-diversity, beta-diversity, and community
      structure. Principal component analysis (PCA) comparing the microbial community
      structures of different datasets, including those with simulated sequencing
      errors, was very reliable. Procrustes analysis showed a high degree of
      concordance between the different datasets for both abundance-weighted and binary
      Jaccard distances (P < 0.05), and a meta-analysis of individual datasets resulted
      in similar conclusions. The Shannon's diversity index was consistent as well,
      with comparable values obtained for the different datasets and for the meta
      analysis of different datasets. In contrast, richness estimators (OTU and Chao)
      varied significantly, and the meta-analysis of richness estimators was also
      biased. The community structures of the two datasets were obviously different and
      led to significant changes in the biomarkers identified by the LEfSe statistical
      tool. CONCLUSIONS: Our results suggest that beta-diversity analysis and Shannon's
      diversity are relatively reliable for meta-analysis, while community structures
      and biomarkers are less consistent. These results should be useful for future
      meta-analyses of microbiomes from different data sources.

PMID- 24034944
TI  - Normative sciatic nerve excursion during a modified straight leg raise test.
AB  - Minimal data exists on how much sciatic nerve motion occurs during straight leg
      raise (SLR). The purpose of this study was to report preliminary normative ranges
      of sciatic nerve excursion using real time ultrasound during a modified SLR. The
      sciatic nerve was scanned in the posterior thigh in sixteen asymptomatic
      participants (age range 19-68 years). Nerve excursion was measured in transverse
      and longitudinal planes during knee extension from 90 degrees  to 0 degrees ,
      with the hip flexed to 30 degrees  and 60 degrees . The ultrasound data was
      analysed off-line using cross correlation software. Results demonstrated that
      most nerves moved superficially during knee extension, a large proportion (10/16)
      moved laterally. Longitudinal excursion ranged from 6.4 to 14.7 mm (mean (SD)
      9.92 mm (2.2)) in 30 degrees  hip flexion, and 5.1-20.2 mm (mean (SD) 12.4 mm
      (4.4)) in 60 degrees  hip flexion. Mean nerve excursion was significantly greater
      in 60 degrees  hip flexion (p = 0.02). There is a large between-subject variation
      in sciatic nerve excursion during this modified SLR in asymptomatic subjects.
      Mean nerve excursion was found to be higher with the hip pre-positioned in
      greater flexion, suggesting that pre-loading may not consistently reduce
      excursion. 

PMID- 24034945
TI  - Intelligent policy making? Key actors' perspectives on the development and
      implementation of an early years' initiative in Scotland's public health arena.
AB  - Increased political enthusiasm for evidence-based policy and action has re
      ignited interest in the use of evidence within political and practitioner
      networks. Theories of evidence-based policy making and practice are being re
      considered in an attempt to better understand the processes through which
      knowledge translation occurs. Understanding how policy develops, and practice
      results, has the potential to facilitate effective evidence use. Further
      knowledge of the factors which shape healthcare delivery and their influence in
      different contexts is needed. This paper explores the processes involved in the
      development of a complex intervention in Scotland's National Health Service
      (NHS). It uses a national oral health programme for children (Childsmile) as a
      case study, drawing upon key actors' perceptions of the influence of different
      drivers (research evidence, practitioner knowledge and values, policy, and
      political and local context) to programme development. Framework analysis is used
      to analyse stakeholder accounts from in-depth interviews. Documentary review is
      also undertaken. Findings suggest that Childsmile can be described as an
      'evidence-informed' intervention, blending available research evidence with
      knowledge from practitioner experience and continual learning through evaluation,
      to plan delivery. The importance of context was underscored, in terms of the need
      to align with prevailing political ideology and in the facilitative strength of
      networks within the relatively small public health community in Scotland.
      Respondents' perceptions support several existing theoretical models of
      translation, however no single theory offered a comprehensive framework covering
      all aspects of the complex processes reported. Childsmile's use of best available
      evidence and on-going contribution to knowledge suggest that the programme is an
      example of intelligent policy making with international relevance. 

PMID- 24034946
TI  - Disembodied abilities: sick role and participation in 'activating' return-to-work
      practices.
AB  - In 'active welfare states', labour participation is regarded essential for being
      part of and contributing to society. In the striving for an increase in labour
      participation of people who were considered (partly) disabled for work, not
      'disabilities', but 'abilities' are put centre stage in vocational rehabilitation
      programmes. In this article we explore what this change in focus means in
      practice. We do this by investigating tensions experienced by participants of
      vocational rehabilitation practices that aim at facilitating return-to-work for
      people with disabilities. Our analysis derives from stories that clients and
      professionals told about daily experiences with disability, vocational
      rehabilitation and (labour) participation. These stories illustrate the logic
      embedded in vocational rehabilitation practices. Our analysis demonstrates that
      this logic, that focuses on will power, stable abilities and employability,
      hampers the realization of labour participation for a part of the population. We
      conclude that a logic of embodiment in which lived experiences of clients are
      acknowledged and in which it is explored what clients are concretely able to do
      in a specific context may be better equipped to facilitate return-to-work. 

PMID- 24034947
TI  - A cluster analytic examination of acculturation and health status among Asian
      Americans in the Washington DC metropolitan area, United States.
AB  - Previous studies reported mixed findings on the relationship between
      acculturation and health status among Asian Americans due to different types of
      acculturation measures used or different Asian subgroups involved in various
      studies. We aim to fill the gap by applying multiple measures of acculturation in
      a diverse sample of Asian subgroups. A cross sectional study was conducted among
      Chinese, Korean and Vietnamese Americans in Washington D.C. Metropolitan Area to
      examine the association between health status and acculturation using multiple
      measures including the Suinn-Lew Asian Self-Identity Acculturation (SL-ASIA)
      scale, clusters based on responses to SL-ASIA, language preference, length of
      stay, age at arrival in the United Sates and self-identity. Three clusters (Asian
      (31%); Bicultural (47%); and American (22%)) were created by using a two-step
      hierarchical method and Bayesian Information Criterion values. Across all the
      measures, more acculturated individuals were significantly more likely to report
      good health than those who were less acculturated after adjusting for covariates.
      Specifically, those in the American cluster were 3.8 times (95% Confidence
      Interval (CI): 2.2, 6.6) more likely and those in the Bicultural cluster were 1.7
      times more likely (95% CI: 1.1, 2.4) to report good health as compared to those
      in the Asian cluster. When the conventional standardized SL-ASIA summary score
      (range:-1.4 to 1.4) was used, a one point increase was associated with 2.2 times
      greater odds of reporting good health (95% CI: 1.5, 3.2). However, the
      interpretation may be challenging due to uncertainty surrounding the meaning of a
      one point increase in SL-ASIA summary score. Among all the measures used,
      acculturation clusters better approximated the acculturation process and provided
      us with a more accurate test of the association in the population. Variables
      included in this measure were more relevant for our study sample and may have
      worked together to capture the multifaceted acculturation process. 

PMID- 24034948
TI  - Social valorisation of stoutness as a determinant of obesity in the context of
      nutritional transition in Cameroon: the Bamileke case.
AB  - Body size perceptions were assessed among members of the Bamileke, an ethnic
      group in an urban setting in Cameroon with high rates of obesity, but also a
      positive perception of stoutness in its social representations. We first
      implemented a qualitative study (April 2007) to identify local representations of
      body weight among Bamileke using semi-structured interviews. We then
      quantitatively assessed body size perceptions among a representative sample of
      Bamileke (May to June 2007), employing a body image assessment scale and a
      questionnaire that included declarative body weight self-satisfaction, health
      status, and attempts to reduce weight. Results indicate Desired Body Size (DBS)
      for women, and particularly for men, was situated in the overweight category.
      Qualitative analyses show that overweight is considered as a normal and healthy
      body size in the Bamileke. On the other hand, the quantitative study reveals that
      high rates of obesity, especially in women (40.8% obese), are associated with
      high blood pressure. Moreover, subjects who had a negative perception of their
      health status wanted to lose weight (p < 0.01). Unlike males, females have a DBS
      lower than their Current Body Size (p < 0.001). In addition, subjects
      (particularly males) who felt they were too lean, were older than those who felt
      too fat. We therefore conclude that the social valorisation of stoutness exposes
      Bamileke, particularly males, to obesity. Although the women stated a desire to
      lose weight and present aesthetic criteria more oriented towards slimness, the
      attitude of the Bamileke remained oriented toward stoutness appreciation. This
      preference can help protect against body image disturbances identified in Western
      societies, but may also increase of the incidence of obesity and its associated
      pathologies in this part of the world. 

PMID- 24034949
TI  - Getting doctors into the bush: general practitioners' preferences for rural
      location.
AB  - A key policy issue in many countries is the maldistribution of doctors across
      geographic areas, which has important effects on equity of access and health care
      costs. Many government programs and incentive schemes have been established to
      encourage doctors to practise in rural areas. However, there is little robust
      evidence of the effectiveness of such incentive schemes. The aim of this study is
      to examine the preferences of general practitioners (GPs) for rural location
      using a discrete choice experiment. This is used to estimate the probabilities of
      moving to a rural area, and the size of financial incentives GPs would require to
      move there. GPs were asked to choose between two job options or to stay at their
      current job as part of the Medicine in Australia: Balancing Employment and Life
      (MABEL) longitudinal survey of doctors. 3727 GPs completed the experiment. Sixty
      five per cent of GPs chose to stay where they were in all choices presented to
      them. Moving to an inland town with less than 5000 population and reasonable
      levels of other job characteristics would require incentives equivalent to 64% of
      current average annual personal earnings ($116,000). Moving to a town with a
      population between 5000 and 20,000 people would require incentives of at least
      37% of current annual earnings, around $68,000. The size of incentives depends
      not only on the area but also on the characteristics of the job. The least
      attractive rural job package would require incentives of at least 130% of annual
      earnings, around $237,000. It is important to begin to tailor incentive packages
      to the characteristics of jobs and of rural areas. 

PMID- 24034950
TI  - A test of the substitution hypothesis: an analysis of urban and rural trends in
      solid/liquid poisoning suicides in Taiwan.
AB  - Taiwan experienced both a significant decrease and a significant increase in the
      suicide rate during the period 1986-1999, which provides a unique opportunity to
      examine the substitution hypothesis in suicide research: that is, whether a
      reduction in the use of a certain method of suicide would be offset by a parallel
      increase in the use of other methods. We also explored whether such method
      substitution, if it existed, differed across urban and rural settings. Data on
      age-, sex-, method-, and urban-/rural-specific suicide rates for the period 1986
      1999 in Taiwan were obtained and the year of 1993 is found to be the inflection
      point. We analyzed using Poisson regression to estimate the average annual
      percentage change (AAPC) for periods of decline (1986-1993) and increase (1993
      1999) in suicides. The rapid decline in suicide by solid/liquid poisoning (mostly
      using pesticides) during a period of accelerated economic development (1986-1999)
      in Taiwan was found to be associated with the increased use of alternative
      methods. An interaction model found a marked decrease in solid/liquid poisoning
      suicide in both urban and rural Taiwan over the period of decline (1986-1993).
      The extent of the decrease was greater in rural areas but was accompanied by a
      rise in the use of several other suicide methods. However, the net effect was
      still a marked reduction in the suicide rate. A general increase in suicide among
      all age groups, for all methods, in both rural and urban settings, and for both
      sexes was found during the period when the suicide rate increased (1993-1999). We
      conclude that restricting access to the means of pesticide suicides reduces not
      only the method-specific suicide rate but also the overall suicide rate;
      nonetheless, suicide method substitution is not an all-or-nothing phenomenon.
      Stratified analyses by geographical (i.e. urban/rural) area can help to
      disentangle the patterns in each subgroup, which will improve our understanding
      of the phenomenon and make suicide prevention efforts more focused and effective.

PMID- 24034951
TI  - Discretion or discretions? Delineating professional discretion: the case of
      English medical practice.
AB  - There has much debate about the extent to which professional discretion has been
      challenged by recent organisational changes such as through the new forms of
      governance associated with the introduction of the principles of the New Public
      Management (NPM) into health systems and other public sector services. What
      appears to be missing from these debates is a detailed analysis of the concept of
      professional discretion itself. This paper attempts to fill this gap by
      delineating the key concepts of professional discretion evident in the literature
      and exploring their significance in an empirical study of the influence of the
      2004 new general medical services contract (nGMS) and the introduction of the
      Quality and Outcomes Framework (QOF), a prescriptive pay-for-performance system
      designed to standardise the quality of care provision in general medical practice
      in the United Kingdom. The study adopted a longitudinal design using semi
      structured interviews with general practitioners (GPs, N = 62) working in the
      English National Health Service (NHS) between 2007 and 2009. A multi-dimensional
      conception of discretion was used to explore how GP discretion might have been
      influenced by contractual changes and in particular, QOF. The findings suggest
      that through a complex interplay of factors, a post-QOF reduction in GP
      discretion was identifiable, highlighting different potential sources of
      constraint such as in the social, organisational and economic dimensions of
      discretion. The evidence also suggested the emergence of a new form of
      organisational medical professionalism within general practice characterised by
      standardisation, bureaucracy and performance management. 

PMID- 24034952
TI  - A geographical perspective on access to sexual and reproductive health care for
      women in rural Africa.
AB  - Utilization of sexual and reproductive health (SRH) services can significantly
      impact health outcomes, such as pregnancy and birth, prenatal and neonatal
      mortality, maternal morbidity and mortality, and vertical transmission of
      infectious diseases like HIV/AIDS. It has long been recognized that access to SRH
      services is essential to positive health outcomes, especially in rural areas of
      developing countries, where long distances as well as poor transportation
      conditions, can be potential barriers to health care acquisition. Improving
      accessibility of health services for target populations is therefore critical for
      specialized healthcare programs. Thus, understanding and evaluation of current
      access to health care is crucial. Combining spatial information using
      geographical information system (GIS) with population survey data, this study
      details a gravity model-based method to measure and evaluate access to SRH
      services in rural Mozambique, and analyzes potential geographic access to such
      services, using family planning as an example. Access is found to be a
      significant factor in reported behavior, superior to traditional distance-based
      indicators. Spatial disparities in geographic access among different population
      groups also appear to exist, likely affecting overall program success. 

PMID- 24034953
TI  - How teams use indicators for quality improvement - a multiple-case study on the
      use of multiple indicators in multidisciplinary breast cancer teams.
AB  - A crucial issue in healthcare is how multidisciplinary teams can use indicators
      for quality improvement. Such teams have increasingly become the core component
      in both care delivery and in many quality improvement methods. This study aims to
      investigate the relationships between (1) team factors and the way
      multidisciplinary teams use indicators for quality improvement, and (2) both team
      and process factors and the intended results. An in-depth, multiple-case study
      was conducted in the Netherlands in 2008 involving four breast cancer teams using
      six structure, process and outcome indicators. The results indicated that the
      process of using indicators involves several stages and activities. Two teams
      applied a more intensive, active and interactive approach as they passed through
      these stages. These teams were perceived to have achieved good results through
      indicator use compared to the other two teams who applied a simple control
      approach. All teams experienced some difficulty in integrating the new formal
      control structure, i.e. measuring and managing performance, in their operational
      task, and in using their 'new' managerial task to decide as a team what and how
      to improve. Our findings indicate the presence of a network of relationships
      between team factors, the controllability and actionability of indicators, the
      indicator-use process, and the intended results. 

PMID- 24034954
TI  - Personal identity and the role of 'carer' among relatives and friends of people
      with multiple sclerosis.
AB  - Informal caregiving continues to be a crucial part of health and social care
      provision in the developed world, but the processes by which the identity of
      informal caregiver is conferred, or assumed, remain unclear. In this article we
      draw on data from a qualitative research study which examined the experiences of
      family members and friends of people with multiple sclerosis (pwMS) to explore
      how they interpret the label 'carer'. We conducted narrative interviews with
      forty people throughout the United Kingdom between June 2011 and January 2012.
      Participants were spouses, partners, parents, children, siblings or friends of
      people who have had multiple sclerosis between 6 months and fifty years. We
      carried out thematic analysis of the interviews, informed by identity theory.
      Identity theory illuminated variation in peoples' perceptions of themselves as
      carers, suggesting that self-identification with the role and label of carer is
      nuanced, shifting and variable. We propose a taxonomy of caring activity
      including emotional support, personal care, physical care, household tasks,
      advocacy and activism and describe four categories, with fluid and overlapping
      boundaries, in which the identity of carer was apparently embraced, enforced,
      absorbed or rejected. Variability and fluidity in self-identification as a carer
      are related to apparent expectations about whether one should assume a caring
      role. Those who were caring from the more tangential (and less taken for granted)
      relationship of sibling or ex-partner were among those who apparently embraced
      the role. Those who were expected to assume the caring role (typically spouses)
      were not always comfortable with doing so. It may be difficult to gain
      acknowledgement from family members and others that they occupy the role of carer
      if people resist the label as a bureaucratisation of their personal
      relationships. 

PMID- 24034955
TI  - A systematic review and meta-analysis of antecedents of blood donation behavior
      and intentions.
AB  - This meta-analysis sought to identify the strongest antecedents of blood donation
      behavior and intentions. It synthesized the results of 24 predictive
      correlational studies of donation behavior and 37 studies of donation intentions.
      The antecedents were grouped into six research programs: (1) the Theory of
      Planned Behavior (TPB) and its extensions, (2) prosocial motivation, (3)
      affective expectations, (4) donor site experience, (5) past donation behavior,
      and (6) donor demographics. Antecedent categories were cross-validated by
      multiple coders, and combined effect sizes were analyzed using a random-effects
      model. For donation behavior, medium positive associations were found with five
      of the constructs from the extended TPB: intentions to donate, perceived
      behavioral control, attitude toward donation, self-efficacy and donor role
      identity. Other antecedents displaying a positive association with donation
      behavior included anticipated regret for not donating, number of past donations
      and donor age. Donor experiences at the collection site in the form of temporary
      deferral or adverse reactions had a medium negative association with behavior.
      For donation intentions, strong positive associations were observed for perceived
      behavioral control, attitude, self-efficacy, role identity and anticipated
      regret. Medium positive associations were observed for personal moral norm,
      subjective norm, satisfaction, and service quality. All other potential
      antecedents had weak or non-significant associations with behavior and
      intentions. Several of these associations were moderated by between-study
      differences, including donor experience, the period of data collection in which
      donation behavior was observed, and the use of a nominal (yes/no return) versus a
      ratio measure of donation behavior. Collectively, the results underscore the
      importance of enhancing donors' attitudes towards donation and building their
      perceived behavioral control and self-efficacy to donate. Further, minimizing the
      risk of adverse reactions and enacting re-recruitment policies for temporarily
      deferred donors will help protect future donation behavior. Implications of these
      findings for blood collection agencies and researchers are discussed. 

PMID- 24034956
TI  - Biogenetic explanations and stigma: a meta-analytic review of associations among
      laypeople.
AB  - The stigma and social rejection faced by people with a mental disorder constitute
      a major barrier to their well-being and recovery. Medicalization has been
      welcomed as a strategy to reduce blame and stigma, although critics have
      cautioned that attributing mental disorders to biogenetic causes may have
      unintended side effects that could exacerbate prejudice and rejection. The
      present study presents a quantitative synthesis of the literature on
      relationships between biogenetic explanations for mental disorders and three key
      elements of stigma, namely blame, perceptions of dangerousness, and social
      distance. A comprehensive search yielded 25 studies meeting the inclusion
      criteria. Separate meta-analyses (Ns = 4278-23,816) were conducted for the three
      stigma types, and assessed the consistency of effects across subgroups of studies
      involving different types of biogenetic explanations, mental disorders, and
      samples. We found that people who hold biogenetic explanations for mental
      disorders tend to blame affected persons less for their problems (r = -0.19), but
      perceive them as more dangerous (r = 0.09) and desire more distance from them (r
      = 0.05). The negative association with blame was significant for schizophrenia,
      belief in genetic causation, and in student samples. The positive association
      with dangerousness was significant for all disorders, belief in general
      biogenetic causation, and in community samples. The positive association with
      social distance was significant for schizophrenia, beliefs in neurochemical and
      general biogenetic causation, and in community samples. Nevertheless, across all
      analyses, biogenetic explanations were only weakly related to stigma. We conclude
      that biogenetic explanations for mental disorders confer mixed blessings for
      stigma. 

PMID- 24034957
TI  - Making information 'relevant': general practitioner judgments and the production
      of patient involvement.
AB  - Sociological work that has engaged with the issue of patient involvement in
      health care suggests it needs to be recognised that decision-making is not simply
      an individual cognitive act contained in a single consultation, but a process
      that is distributed across multiple encounters in relation to a range of agents
      and non-human actors. Drawing on such conceptualisations of decision-making, and
      based on semi-structured interviews with 24 General Practitioners (GPs) in the
      United Kingdom about the prescription of statins for the primary prevention of
      cardiovascular disease, this paper explores the preemptive work that GPs perform
      when attempting to achieve patient involvement in healthcare decisions. The paper
      identifies a set of repertoires through which they evaluate and coordinate often
      contradictory forms of knowledge, transforming them into information that they
      think is relevant to patients, and which will potentially facilitate meaningful
      involvement in healthcare decisions. The study concludes by suggesting that such
      fluid and context sensitive practices are a necessary strategy for navigating
      complex health environments, which can be justified and underpinned by a
      relational model of autonomy. However, work needs to be done to explore how such
      judgments can be calibrated to mesh with the decision-making preferences of
      patients and what new approaches and standards for practice this would require. 

PMID- 24034958
TI  - Early supplementary feeding among central African foragers and farmers: a
      biocultural approach.
AB  - The World Health Organization (WHO) recommends exclusive breastfeeding (EBF) for
      six months, yet this recommendation has proven difficult to implement. Here, we
      examine the nature of and influences on early supplementation (ES) in light of
      current evidence regarding evolved human caregiving patterns (cooperative
      breeding). We utilize a biocultural approach, which takes into consideration that
      infant feeding is influenced by an array of evolutionary, physiological,
      structural, ecological, and cultural factors. The research is cross-cultural,
      conducted among the Aka foragers and Ngandu farmers in the Central African
      Republic. We explore emic perspectives of ES as well as infant characteristics
      and socioecological factors that, when combined with evidence of human care
      patterns, offers a more holistic understanding of early infant feeding. We employ
      a mixed-methods approach, utilizing qualitative interview and quantitative focal
      follow behavioral observation data, collected from 2009 to 2012. Results indicate
      that foragers introduce ES earlier than farmers; nevertheless, only a small
      proportion of Ngandu mothers EBF. Maternal and non-maternal caregiver ES patterns
      are predicted by different factors. Maternal ES is associated with infant age,
      while non-maternal ES is associated with maternal labor activities and the
      infant's caregiving network. Non-maternal ES, but not maternal ES, reduces
      breastfeeding. Results suggest that neither subsistence ecology nor maternal
      labor patterns fully explain the timing of ES. However, cooperative caregiving,
      infant mortality risk, and cultural models of caregiving offer insights into why
      foragers commence ES so early. We discuss the implications of ES on weaning age,
      inter-birth intervals, and fertility. Throughout our evolutionary history and
      today, non-maternal caregivers were and are essential participants in childcare
      and provisioning, yet are rarely viewed as active participants in early infant
      feeding. Consideration of evolved caregiving patterns and the role of others in
      feeding practice will enhance public health outreach. 

PMID- 24034959
TI  - Biomedicalization and the public sphere: newspaper coverage of health and
      medicine, 1960s-2000s.
AB  - This article examines historical trends in the reporting of health and medicine
      in The New York Times and Chicago Tribune from the 1960s to the 2000s. It focuses
      on the extent to which health reporting can be said to have become increasingly
      politicized, or to have shifted from treating the production of medical knowledge
      as something belonging to a restricted, specialized sphere, to treating it as a
      part of the general arena of public debate. We coded a sample of 400 stories from
      the two newspapers for four different Implied Audiences which health stories can
      address: Scientific/Professional, Patient/Consumer, Investor and
      Citizen/Policymaker. Stories were also coded for the origin of the story, the
      sources cited, the presence of controversy, and the positive or negative
      representation of biomedical institutions and actors. The data show that through
      all five decades, news reporting on health and medicine addressed readers as
      Citizen/Policymakers most often, though Patient/Consumer and Investor-oriented
      stories increased over time. Biomedical researchers eclipsed individual
      physicians and public health officials as sources of news, and the sources
      diversified to include more business sources, civil society organizations and
      patients and other lay people. The reporting of controversy increased, and
      portrayals of biomedicine shifted from lopsidedly positive to more mixed. We use
      these data in pinpointing how media play a constitutive role in the process of
      "biomedicalization," through which biomedicine has both extended its reach into
      and become entangled with other spheres of society and of knowledge production. 

PMID- 24034960
TI  - The effect of physical activity on long-term income.
AB  - Empirical evidence for the direct effects of physical activities on long-term
      labor market outcomes is limited. This state of affairs is surprising, because
      there is a growing amount of support on the positive effects of physical
      activities on health on the one hand and on the effects of good health on labor
      market outcomes on the other hand. We examine the long-term income effects of
      physical activity using a large sample (N = 5042) of male twins from Finland
      (Older Finnish Twin Cohort Study, 1975, 1981, 1990), matched to detailed register
      based income data (Finnish Longitudinal Employer-Employee Data, 1990-2004). Our
      primary income measure is calculated over a fifteen-year period and it covers the
      prime working age of the twins that we study. We use the twin dimension of the
      data to control for unobservable genetic and family confounding factors. Our
      within-twin estimates show that being physically active has a positive impact on
      the long-term income. We argue that our results are not easily reconciled with
      the intuitive explanation of physical activity enhancing long-term income via
      health or more intense labor market attachment. We reason that instead, there may
      be various non-cognitive mechanisms at work: Physical activity can, for example,
      make people more persistent in the face of work-related difficulties and increase
      their desire to partake in competitive situations, with greater expected
      pecuniary rewards. 

PMID- 24034961
TI  - Parents' and professionals' perceptions of family-centered care for children with
      autism spectrum disorder across service sectors.
AB  - Family-centered care (FCC) has been linked with improved parent and child
      outcomes, yet its implementation can be challenging due to family, professional,
      organizational and systemic factors and policies. This study aims to increase
      knowledge and understanding of how families with children with autism spectrum
      disorder (ASD) experience FCC in Alberta, Canada. 152 parents with a child with
      ASD completed the Measure of Processes of Care, separately for each utilized
      service sector, and 146 professionals working with persons with ASD completed the
      Measure of Processes of Care - Service Providers. Additionally, in-depth
      interviews were conducted with a sub-sample of 19 parents, purposefully sampled
      for diversity in child and family characteristics. Data were collected in 2011.
      Descriptive and inferential statistics were used to analyze quantitative data.
      Interview transcripts were analyzed using grounded theory constant comparison
      methods, yielding a data generated theoretical model depicting families'
      experiences with FCC over time and across service sectors. There were no
      statistically significant differences in FCC scores across service sectors, but
      statistically significant differences in FCC scores between parents' and
      professionals' were found. Qualitative data revealed positive experiences and
      perceptions of receiving FCC from professionals "on the ground" across sectors,
      but negative experiences and perceptions of FCC at the systems level (i.e.,
      administration, funders). These broad experiences emerged as a core theme "System
      of Exclusion", which integrated the key themes: (1) "The Fight", (2) "Roles and
      Restrictions of Care", and (3) "Therapeutic Rapport". Professionals and service
      providers can use findings to ensure that services reflect current
      conceptualizations of FCC, and decision and policy makers can use findings to
      recognize systemic barriers to implementing FCC and inform policy change. 

PMID- 24034962
TI  - The evolving concept of "patient-centeredness" in patient-physician communication
      research.
AB  - Over the past few decades, the concept of "patient-centeredness" has been
      intensively studied in health communication research on patient-physician
      interaction. Despite its popularity, this concept has often been criticized for
      lacking a unified definition and operationalized measurement. This article
      reviews how health communication research on patient-physician interaction has
      conceptualized and operationalized patient-centered communication based on four
      major theoretical perspectives in sociology (i.e., functionalism, conflict
      theory, utilitarianism, and social constructionism), and discusses the agenda for
      future research in this field. Each theory addresses different aspects of the
      patient-physician relationship and communication from different theoretical
      viewpoints. Patient-centeredness is a multifaceted construct with no single
      theory that can sufficiently define the whole concept. Different theoretical
      perspectives of patient-centered communication can be selectively adopted
      according to the context and nature of problems in the patient-physician
      relationship that a particular study aims to explore. The present study may
      provide a useful framework: it offers an overview of the differing models of
      patient-centered communication and the expected roles and goals in each model; it
      does so toward identifying a communication model that fits the patient and the
      context and toward theoretically reconstructing existing measures of patient
      centered communication. Furthermore, although patient-centered communication has
      been defined mainly from the viewpoint of physician's behaviors aimed at
      achieving patient-centered care, patient competence is also required for patient
      centered communication. This needs to be examined in current medical practice. 

PMID- 24034964
TI  - The impact of psychological trauma on wages in post-conflict Bosnia and
      Herzegovina.
AB  - In the last three decades, armed conflict has increasingly been fought among
      civilian populations, resulting in greater physical and mental tolls. Soldiers
      returning from combat with psychological trauma are now receiving medical and
      policy attention for reintegration into the workforce. However, there is little
      attention on the impacts and options available to civilians who may face similar
      problems achieving labor force success after exposure to war-related trauma.
      Using the Bosnia and Herzegovina Living Standards Measurement Survey for years
      2001-2004, we study wage attainment for 7659 respondents in relation to a series
      of psychological trauma measures which correspond to those used in PTSD
      diagnosis. In standard OLS regression, all subcomponents of PTSD have a negative
      impact; however, once unobserved individual heterogeneity is taken into account,
      some of the individual elements of psychological trauma have positive impacts on
      wage attainment. This is one of the first studies to find evidence of
      Posttraumatic Growth using information beyond psychometric instruments. The
      impact of the PTSD condition itself is insignificant in both models, and we do
      not find evidence of selection bias. We determine that the traditional means of
      predicting wages in labor economics are relevant in a post-conflict environment. 

PMID- 24034963
TI  - Effects of an HIV peer prevention intervention on sexual and injecting risk
      behaviors among injecting drug users and their risk partners in Thai Nguyen,
      Vietnam: a randomized controlled trial.
AB  - Globally, 30% of new HIV infections outside sub-Saharan Africa involve injecting
      drug users (IDU) and in many countries, including Vietnam, HIV epidemics are
      concentrated among IDU. We conducted a randomized controlled trial in Thai
      Nguyen, Vietnam, to evaluate whether a peer oriented behavioral intervention
      could reduce injecting and sexual HIV risk behaviors among IDU and their network
      members. 419 HIV-negative index IDU aged 18 years or older and 516 injecting and
      sexual network members were enrolled. Each index participant was randomly
      assigned to receive a series of six small group peer educator-training sessions
      and three booster sessions in addition to HIV testing and counseling (HTC)
      (intervention; n = 210) or HTC only (control; n = 209). Follow-up, including HTC,
      was conducted at 3, 6, 9 and 12 months post-intervention. The proportion of
      unprotected sex dropped significantly from 49% to 27% (SE (difference) = 3%, p <
      0.01) between baseline and the 3-month visit among all index-network member
      pairs. However, at 12 months, post-intervention, intervention participants had a
      14% greater decline in unprotected sex relative to control participants (Wald
      test = 10.8, df = 4, p = 0.03). This intervention effect is explained by trial
      participants assigned to the control arm who missed at least one standardized HTC
      session during follow-up and subsequently reported increased unprotected sex. The
      proportion of observed needle/syringe sharing dropped significantly between
      baseline and the 3-month visit (14% vs. 3%, SE (difference) = 2%, p < 0.01) and
      persisted until 12 months, but there was no difference across trial arms (Wald
      test = 3.74, df = 3, p = 0.44). 

PMID- 24034965
TI  - Neighborhood cohesion and daily well-being: results from a diary study.
AB  - Neighborly cohesiveness has documented benefits for health. Furthermore, high
      perceived neighborhood cohesion offsets the adverse health effects of
      neighborhood socioeconomic adversity. One potential way neighborhood cohesion
      influences health is through daily stress processes. The current study uses
      participants (n = 2022, age 30-84 years) from The Midlife in the United States II
      and the National Study of Daily Experiences II, collected between 2004 and 2006,
      to examine this hypothesis using a within-person, daily diary design. We
      predicted that people who perceive high neighborhood cohesion are exposed to
      fewer daily stressors, such as interpersonal arguments, lower daily physical
      symptoms and negative affect, and higher daily positive affect. We also
      hypothesized that perceptions of neighborhood cohesion buffer decline in
      affective and physical well-being on days when daily stressors do occur. Results
      indicate that higher perceived neighborhood cohesion predicts fewer self-reported
      daily stressors, higher positive affect, lower negative affect, and fewer
      physical health symptoms. High perceived neighborhood cohesion also buffers the
      effects of daily stressors on negative affect, even after adjusting for other
      sources of social support. Results from the present study suggest interventions
      focusing on neighborhood cohesion may result in improved well-being and may
      minimize the adverse effect of daily stressors. 

PMID- 24034966
TI  - Dietary inequalities of mother-child pairs in the rural Amazon: evidence of
      maternal-child buffering?
AB  - This paper explores the expected outcome of maternal nutritional "buffering,"
      namely that children's diets will be more adequate than mothers' diets under
      conditions of food scarcity. Data on Amazonian mothers and their children,
      household demography and economics and direct, weighed measures of household food
      availability and dietary intakes of mother-child pairs were collected from 51
      households to address the following research questions: (1) is there evidence of
      food scarcity in this setting?; (2) are there differences in energy and protein
      adequacy between children and their mothers?; and, (3) which individual and
      household-level factors are associated with these mother-child differences in
      energy and protein adequacy? In this context of food scarcity, we found that the
      majority of children had more adequate energy (p < 0.001) and protein (p < 0.001)
      intakes than their mothers. Multivariate OLS regression models showed that of the
      individual-level factors, child age and height-for-age were negatively associated
      with maternal-child energy and protein inequalities while maternal reproductive
      status (lactation) was positively associated with energy inequality. While there
      were no gender differences in dietary adequacy among children, boys had a larger
      advantage over their mothers in terms of protein adequacy than girls. Household
      food availability was related to maternal-child energy and protein inequalities
      in a curvilinear fashion with the lowest inequalities found in households with
      extremely low food availability and those with adequate food resources. This is
      the first study to quantify maternal-child dietary inequalities in a setting of
      food scarcity and demonstrates the importance of the household context and
      individual characteristics in understanding the degree to which mothers protect
      their children from resource scarcity. 

PMID- 24034967
TI  - Managing misaligned paternity findings in research including sickle cell disease
      screening in Kenya: 'consulting communities' to inform policy.
AB  - The management of misaligned paternity findings raises important controversy
      worldwide. It has mainly, however, been discussed in the context of high-income
      countries. Genetic and genomics research, with the potential to show misaligned
      paternity, are becoming increasingly common in Africa. During a genomics study in
      Kenya, a dilemma arose over testing and sharing information on paternal sickle
      cell disease status. This dilemma may be paradigmatic of challenges in sharing
      misaligned paternity findings in many research and health care settings. Using a
      deliberative approach to community consultation to inform research practice, we
      explored residents' views on paternal testing and sharing misaligned paternity
      information. Between December 2009 and November 2010, 63 residents in Kilifi
      County were engaged in informed deliberative small group discussions, structured
      to support normative reflection within the groups, with purposive selection to
      explore diversity. Analysis was based on a modified framework analysis approach,
      drawing on relevant social science and bioethics literature. The methods
      generated in-depth individual and group reflection on morally important issues
      and uncovered wide diversity in views and values. Fundamental and conflicting
      values emerged around the importance of family interests and openness,
      underpinned by disagreement on the moral implications of marital infidelity and
      withholding truth. Wider consideration of ethical issues emerging in these
      debates supports locally-held reasoning that paternal sickle cell testing should
      not be undertaken in this context, in contrast to views that testing should be
      done with or without the disclosure of misaligned paternity information. The
      findings highlight the importance of facilitating wider testing of family members
      of affected children, contingent on the development and implementation of
      national policies for the management of this inherited disorder. Their richness
      also illustrates the potential for the approach adopted in this study to
      strengthen community consultation. 

PMID- 24034969
TI  - Advancing our understanding of sibling supervision and injury risk for young
      children.
AB  - Sibling supervision has been shown to increase the risk of supervisee's
      unintentional injury in the home. Both poorer supervision by the older sibling
      and noncompliance by the younger sibling have been shown to contribute to this
      risk. Previous studies have shown that informing older siblings that they are
      responsible for the behavior of their younger sibling improves their supervision.
      The present study, conducted in Canada, examined whether informing both children
      the older child is in charge would improve both older sibling supervisory
      practices and compliance by the younger child. Younger and older siblings were
      initially placed in a room containing contrived hazards, and their interactions
      were unobtrusively recorded. In a second contrived hazards room, both children
      were then informed that the older sibling was in charge, and the supervisor was
      privately told not to let the supervisee touch hazardous objects. Results
      revealed that sibling supervisors showed improved supervision but supervisee
      behavior did not vary across conditions. Implications for injury prevention and
      future research directions are discussed. 

PMID- 24034968
TI  - Specificity of early movie effects on adolescent sexual behavior and alcohol use.
AB  - Adolescents' movie sex exposure (MSE) and movie alcohol exposure (MAE) have been
      shown to influence later sexual behavior and drinking, respectively. No study to
      date, however, has tested whether these effects generalize across behaviors. This
      study examined the concurrent influences of early (i.e., before age 16) MSE and
      MAE on subsequent risky sex and alcohol use among a national sample of 1228 U.S.
      adolescents. Participants reported their health behaviors and movie viewing up to
      six times between 2003 and 2009 in telephone interviews. The Beach method was
      used to create a population-based estimate of each participant's MSE and MAE,
      which were then entered into a structural equation model (SEM) to predict
      lifetime risky sex and past month alcohol use at ages 18-21. For both men and
      women, MAE predicted alcohol use, mediated by age of initiation of heavy episodic
      drinking (HED) and age of sexual debut; MAE also predicted risky sex via age of
      sexual debut. Among men only, MSE indirectly predicted risky sex and alcohol use.
      Findings indicated that early exposure to risk content from movies had both
      specific and general effects on later risk-taking, but gender differences were
      evident: for men, MSE was a stronger predictor than MAE, but for women, only MAE
      predicted later risk behavior. These results have implications for future media
      research, prevention programs for adolescent sex and alcohol use, and movie
      ratings that can guide parents' decisions as to which movies are appropriate for
      their children. 

PMID- 24034970
TI  - Management strategy of pulmonary nodule in 2013.
AB  - Lung nodules are commonly found on computed tomography (CT) and need a
      standardized approach in order to avoid misdiagnosing lung cancer and delaying
      surgical excision whilst simultaneously avoiding unnecessary invasive procedures
      if the lesions prove to be benign. Great advances have been made in the last
      decade in various areas affecting the management of lung nodules: the
      understanding of the molecular mechanisms behind carcinogenesis, a new
      classification of lung adenocarcinoma, new data on lung cancer screening,
      widespread use of multi-detector row CT and development of volumetric analysis
      software for nodules. Recent decision-making algorithms are based on the size,
      density and follow-up of the nodule. The distinction between solid nodules, sub
      solid nodules and pure ground glass nodules is fundamental, and has a strong
      correlation with the histologic spectrum of adenocarcinoma. In the absence of
      criteria suggesting benign disease, the radiologist's report should offer one of
      the following two options: follow-up based on the recommendations if the nodule
      is equivocal, or multidisciplinary discussion to consider invasive management if
      the nodule is highly suspicious of malignancy. Recent data from this statement
      are reviewed and practical guidelines are offered based on international expert
      consensus opinion. 

PMID- 24034972
TI  - Authors miss the opportunity to discuss important public health implications.

PMID- 24034971
TI  - Peptide receptor radionuclide therapy of neuroendocrine tumors with (90)Y
      DOTATOC: is treatment response predictable by pre-therapeutic uptake of (68)Ga
      DOTATOC?
AB  - PURPOSE: PET with (68)Ga-DOTATOC allows for imaging and quantitative assessment
      of somatostatin receptor expression in neuroendocrine tumors (NET). The aim of
      this retrospective study was to analyze whether pre-therapeutic (68)Ga-DOTATOC
      PET/CT is able to predict response to Peptide Receptor Radionuclide Therapy
      (PRRT). PATIENTS AND METHODS: Forty patients with advanced stage NET were treated
      with a fixed dose of (90)Y-DOTATOC (5550 or 3700MBq). Prior to PRRT, each patient
      received (68)Ga-DOTATOC PET/CT. Treatment results were evaluated after 3months by
      CT, tumor marker levels and clinical course and correlated with (68)Ga-DOTATOC
      uptake (SUVmax) and the assumed uptake of (90)Y-DOTATOC in tumor manifestations
      (MBq/g). ROC analysis and pairwise comparison of area under the curve (AUC) were
      performed with pre-treatment uptake of (68)Ga-DOTATOC, assumed uptake of (90)Y
      DOTATOC and treatment activity alone and in relation to body weight as continuous
      variables, and response/no response as classification variable. RESULTS:
      According to conventional criteria (tumor shrinkage, decrease of tumor markers,
      improved or stable clinical condition), 20 patients were classified as
      responders, 16 as non-responders and in four patients findings were equivocal.
      Using a SUV more than 17.9 as cut-off for favorable outcome, PET was able to
      predict treatment response of all responders and 15 out of 16 non-responders. All
      four patients with equivocal findings showed SUV less than or equal to 17.9 and
      soon experienced tumor progression. The assumed uptake of (90)Y-DOTATOC in tumor
      manifestations using a cut-off more than 1.26MBq/g as predictor of response was
      able to correctly classify 19 out of 20 responders, and 14 out of 16 non
      responders. In all patients with equivocal findings, the assumed uptake of (90)Y
      DOTATOC was below 1.26MBq/g. CONCLUSION: Pre-therapeutic (68)Ga-DOTATOC tumor
      uptake as well as assumed uptake of (90)Y-DOTATOC are strongly associated with
      the results of subsequent PRRT. The defined cut-off values should be confirmed by
      prospective studies and may then provide the rationale for individual dosing and
      selecting patients with high likelihood of favorable treatment outcome.

PMID- 24034973
TI  - Two-dimensional high-performance thin-layer chromatography of tryptic bovine
      albumin digest using normal- and reverse-phase systems with silanized silica
      stationary phase.
AB  - Among many advantages of planar techniques, two-dimensional (2D) separation seems
      to be the most important for analysis of complex samples. Here we present quick,
      simple and efficient two-dimensional high-performance thin-layer chromatography
      (2D HPTLC) of bovine albumin digest using commercial HPTLC RP-18W plates (silica
      based stationary phase with chemically bonded octadecyl ligands of coverage
      density 0.5MUmol/m(2) from Merck, Darmstadt). We show, that at low or high
      concentration of water in the mobile phase comprised methanol and some additives
      the chromatographic systems with the plates mentioned demonstrate normal- or
      reversed-phase liquid chromatography properties, respectively, for separation of
      peptides obtained. These two systems show quite different separation selectivity
      and their combination into 2D HPTLC process provides excellent separation of
      peptides of the bovine albumin digest. 

PMID- 24034974
TI  - Fast comprehensive two-dimensional gas chromatography method for fatty acid
      methyl ester separation and quantification using dual ionic liquid columns.
AB  - Safflower oil is a complex mixture of C18 saturated and unsaturated fatty acids
      amongst other fatty acids, and achieving separation between these similar
      structure components using one dimensional gas chromatography (GC) may be
      difficult. This investigation aims to obtain improved separation of fatty acid
      methyl esters in safflower oil, and their quantification using comprehensive two
      dimensional GC (GC*GC). Here, GC*GC separation is accomplished by the coupling of
      two ionic liquid (IL) column phases: the combination of SLB-IL111 with IL59
      column phases was finally selected since it provided excellent separation of a
      FAME standard mixture, as well as fatty acids in safflower and linseed oil,
      compared to other tested column sets. Safflower oil FAME were well separated in a
      short run of 16min. FAME validation was demonstrated by method reproducibility,
      linearity over a range up to 500mgL(-1), and limits of detection which ranged
      from 1.9mgL(-1) to 5.2mgL(-1) at a split ratio of 20:1. Quantification was
      carried out using two dilution levels of 200-fold for major components and 20
      fold for trace components. The fatty acids C15:0 and C17:0 were not reported
      previously in safflower oil. The SLB-IL111/IL59 column set proved to be an
      effective and novel configuration for separation and quantification of vegetable
      and animal oil fatty acids. 

PMID- 24034975
TI  - Microcalorimetric study of the adsorption of lactoferrin in supermacroporous
      continuous cryogel with immobilized Cu(2+) ions.
AB  - The adsorption affinity of lactoferrin from whey in monolithic supermacroporous
      cryogel was analyzed using equilibrium data adsorptive isothermal titration
      microcalorimetry to measure thermodynamic information governing the process.
      Isotherm data was obtained at temperatures of 20, 30 and 40 degrees C, pH 6, 7
      and 8, and ionic strength of 200, 600 and 1000mmolL(-1) NaCl. The Langmuir model
      was fitted to equilibrium data. The binding was tighter at higher temperatures.
      The adsorption of protein was observed as spontaneous in all cases analyzed. The
      microcalorimetric study indicated that, in most cases examined, the adsorption of
      the protein in the matrix was entropy and enthalpy favored and entropy driven.
      Results provide data to enable the improvement of technical processes for the
      affinity separation of proteins. 

PMID- 24034976
TI  - Planar chromatography mediated screening of tetracycline and fluoroquinolone
      antibiotics in milk by fluorescence and mass selective detection.
AB  - A rapid and efficient method for preliminary screening of four tetracyclines
      (tetracycline, chlortetracycline, oxytetracycline, doxycline) and three
      fluoroquinolones (enrofloxacin, ciprofloxacin, marbofloxacin), mostly detected in
      milk, by high-performance thin-layer chromatography-fluorescence detection and
      electrospray ionization mass spectrometry (HPTLC-FLD-ESI/MS) is highlighted. The
      optimized separation of the target antibiotics on ethylenediamine tetraacetic
      acid modified silica gel plates showed marked benefits for screening purposes.
      Besides, selective and sensitive densitometry in fluorescence mode was
      established with excitation at 366nm for the tetracyclines, 300nm for
      enrofloxacin and ciprofloxacin, and 280nm for marbofloxacin. Limits of detection
      (LOD) and quantitation (LOQ) with 95% confidence were in the range of 12-25 and
      45-95MUg/kg, respectively, in milk samples. Recoveries of target antibiotics from
      milk samples spiked at three critical levels (50, 100 and 150MUg/kg) ranged from
      76% to 105%. More importantly, a mass selective detection (MSD) was established
      as additional tool for confirmatory purposes. Using the elution-head based TLC-MS
      interface, the optimized elution flow consisting of acetonitrile/ammonium formate
      buffer (9/1, v/v) at a rate of 0.3mL/min enabled time-dependent resolution of
      analytes from the major interfering compounds, thus circumventing serious ion
      suppression effects. The established MSD assay also offered high sensitivity
      (25MUg/kg) for confirmation, meeting Commission Regulation (EU) No. 37/2010. 

PMID- 24034977
TI  - Synthesis of molecularly imprinted polymer sorbents and application for the
      determination of aminoglycosides antibiotics in honey.
AB  - Aminoglycoside antibiotic (AA)-selective molecularly imprinted polymer (MIP)
      sorbent was synthesized by polymerization of methacrylic acid and ethylene glycol
      dimethacrylate in the presence of streptomycin as template molecule. The MIP
      sorbent was in detail characterized and its performance was evaluated by
      selecting four model AAs including streptomycin, gentamicin, spectinomycin and
      dihydrostreptomycin. Relative to non-imprinted polymer (NIP), the MIPs exhibited
      much higher recognizable capacity and specificity to the AAs and negligible
      adsorption for non-AAs as well. In combination of hydrophilic interaction liquid
      chromatography-tandem mass spectrometry (HILIC-MS/MS), the MIP sorbent-based
      solid phase extraction (SPE) was able to effectively determine the residue of
      four model AAs in honey samples with recovery ranging from 90% to 110%. The limit
      of detection (and the limit of quantitation) of streptomycin, gentamicin,
      spectinomycin and dihydrostreptomycin was 4.5 (15.0), 2.4 (8.0), 6.0 (20.0) and
      1.8 (6.0) MUg/kg, respectively. Relative standard deviations of intraday and
      inter-day assay under three spiked levels were 4.4-12.0% and 6.8-14.6%,
      respectively.

PMID- 24034978
TI  - Advances in the development of organic polymer monolithic columns and their
      applications in food analysis--a review.
AB  - Monolithic continuous separation media are gradually finding their way to sample
      pre-treatment, isolation, enrichment and final analytical separations of a
      plethora of compounds, occurring as food components, additives or contaminants,
      including pharmaceuticals, pesticides and toxins, which have traditionally been
      the domain of particulate chromatographic materials. In the present review,
      recent advances in the technology of monolithic columns and the applications in
      food analysis are addressed. Silica-based monoliths are excellent substitutes to
      conventional particle-packed columns, improving the speed of analysis for low
      molecular weight compounds, due to their excellent efficiency and high
      permeability. These properties have been recently appreciated in two-dimensional
      HPLC, where the performance in the second dimension is of crucial importance.
      Organic-polymer monoliths in various formats provide excellent separations of
      biopolymers. Thin monolithic disks or rod columns are widely employed in
      isolation, purification and pre-treatment of sample containing proteins, peptides
      or nucleic acid fragments. Monolithic capillaries were originally intended for
      use in electrochromatography, but are becoming more frequently used for capillary
      and micro-HPLC. Monoliths are ideal highly porous support media for
      immobilization or imprinting template molecules, to provide sorbents for shape
      selective isolation of target molecules from various matrices occurring in food
      analysis. The separation efficiency of organic polymer monoliths for small
      molecules can be significantly improved by optimization of polymerization
      approach, or by post-polymerization modification. This will enable full
      utilization of a large variety of available monomers to prepare monoliths with
      chemistry matching the needs of selectivity of separations of various food
      samples containing even very polar or ionized compounds. 

PMID- 24034979
TI  - Response to "authors miss the opportunity to discuss important public health
      implications".

PMID- 24034981
TI  - Assessing the precision of strain measurements using electron backscatter
      diffraction--part 2: experimental demonstration.
AB  - The residual impression after performing a microhardness indent in silicon has
      been mapped with high resolution EBSD to reveal residual elastic strain and
      lattice rotation fields. Mapping of the same area has been performed with
      variable pattern binning and exposure times to reveal the qualitative and
      quantitative differences resulting from reducing the pattern size and exposure
      time. Two dimension 'image' plots of these fields indicate that qualitative
      assessment of the shape and size of the fields can be performed with as much as
      4*4 binning. However, quantitative assessment using line scans reveals that the
      smoothest profile can be obtained using minimal pattern binning and long exposure
      times. To compare and contrast with these experimental maps, finite element
      analysis has been performed using a continuum damage-plasticity material law
      which has been independently calibrated to Si [9]. The constitutive law
      incorporates isotropic hardening in compression, and isotropic hardening and
      damage in tension. To accurately capture the localised damage which develops
      during indentation via the nucleation and propagation of cracks around the
      indentation site cohesive elements were assigned along the interfaces between the
      planes which experience the maximum traction. The residual strain state around
      the indenter and the size of the cracks agree very well with the experimentally
      measured value. 

PMID- 24034980
TI  - Hepatic pseudocystic metastasis of well-differentiated ileal neuroendocrine
      tumor: a case report with review of the literature.
AB  - Imaging appearance of cyst-like changes is most frequently described in primary
      neuroendocrine lesions, especially pancreatic NETs.The imaging finding of a
      pseudocystic lesion of the liver puts in differential diagnosis many pathologies
      such as infectious diseases, simple biliary cysts up to biliary cystadenomas and
      eventually to primary or metastatic malignancies.Primary or metastatic hepatic
      malignancies with pseudocystic aspects are rare, and a pseudocystic aspect is
      reported only after neo-adjuvant treatment.Liver metastasis of untreated
      neuroendocrine tumors are usually solid and, to our knowledge, only two cases of
      neuroendocrine cystic hepatic metastases of ileal atypical carcinoids have been
      reported so far.We present a case of a 67 years old man with synchronous finding
      of an untreated hepatic pseudocystic lesion and an ileal mass histologically
      diagnosed as a well differentiated (G1) neuroendocrine tumor. VIRTUAL SLIDES: The
      virtual slides for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/1443883503102967.

PMID- 24034982
TI  - Dating the Lower to Middle Paleolithic transition in the Levant: a view from
      Misliya Cave, Mount Carmel, Israel.
AB  - The transition from the Lower to the Middle Paleolithic in the Levant is a
      crucial event in human evolution, since it may involve the arrival of a new human
      population. In the current study, we present thermoluminescence (TL) dates
      obtained from 32 burnt flints retrieved from the late Lower Paleolithic (Acheulo
      Yabrudian) and Early Middle Paleolithic (Mousterian) layers of Misliya Cave,
      Mount Carmel, Israel. Early Middle Paleolithic industries rich in Levallois and
      laminar products were assigned mean ages ranging from ~250 to ~160 ka (thousands
      of years ago), suggesting a production of this industry during MIS 7 and the
      early part of MIS 6. The mean ages obtained for the samples associated with the
      Acheulo-Yabrudian (strengthened by an isochron analysis) indicate a production of
      this cultural complex ~250 ka ago, at the end of MIS 8. According to the Misliya
      TL dates, the transition from the Lower to the Middle Paleolithic in the site
      took place at the limit MIS 8/7 or during the early part of MIS 7. The dates,
      together with the pronounced differences in lithic technology strongly suggest
      the arrival of a new population during this period.

PMID- 24034983
TI  - New evidence for diet and niche partitioning in Rudapithecus and Anapithecus from
      Rudabanya, Hungary.
AB  - Rudabanya is rare among Eurasian Miocene fossil primate localities in preserving
      both a hominid and pliopithecoid, and as such provides the unique opportunity to
      reconstruct the nature of sympatry and niche partitioning in these taxa.
      Rudapithecus and Anapithecus have similar locomotor and positional behavior and
      overlapping body mass ranges. While prior analyses of molar occlusal anatomy and
      microwear identify Rudapithecus as a soft-object frugivore, reconstructing the
      dietary behavior of Anapithecus has been more problematic. This taxon has been
      interpreted to be more folivorous by some, and more frugivorous by others. Here,
      we use high-resolution polynomial curve fitting (HR-PCF) to quantify and evaluate
      the mesiodistal and cervico-incisal curvatures of the incisor crowns of
      Rudapithecus and Anapithecus to identify diet-specific morphological variation in
      these taxa. Results are consistent with the interpretation that Anapithecus and
      Rudapithecus were primarily frugivorous and had diets that included similar
      resource types. However, Anapithecus may have consumed greater amounts of
      foliage, similar to extant mixed folivore-frugivores (i.e., Gorilla gorilla
      gorilla, Symphalangus syndactylus), while Rudapithecus generated elevated
      compressive loads in the incisor region consistent with a specialized role for
      the anterior dentition in food processing (i.e., removal of tough protective
      fruit pericarps). We interpret these findings in light of the paleoecology at
      Rudabanya and conclude that, if these taxa were indeed sympatric, Anapithecus may
      have used additional leaf consumption as a seasonal fallback resource to avoid
      direct competition with Rudapithecus. Conversely, Rudapithecus may have relied on
      less preferred and harder fruiting resources as a seasonal fallback resource
      during periods of fruit scarcity. 

PMID- 24034984
TI  - Response to "Comment on Specific binding of hydroxylated polychlorinated biphenyl
      metabolites and other substances to bovine calf uterine estrogen receptor:
      structure-binding relationships [Kramer and Giesy, Sci Total Environ 1999;233:141
      61]".

PMID- 24034986
TI  - Removal of the insect repellent N,N-diethyl-m-toluamide (DEET) by laccase
      mediated systems.
AB  - Numerous efforts have been made to remove emerging trace organic contaminants,
      such as pharmaceuticals and personal care products (PPCPs). This study examined
      the removal of N,N-diethyl-m-toluamide (DEET) by Trametes versicolor laccase and
      its laccase-mediator systems. Experimental results showed that DEET was poorly
      removed by laccase alone. The poor removal efficiency of DEET by laccase may be
      attributed to the presence of strong withdrawing electron group (-CO-N [CH2
      CH3]2) in the chemical structure of DEET. Experimental results also indicated
      that DEET might be indirectly oxidized by laccase-mediator systems. More than 50%
      initial DEET amount was removed by laccase in the presence of a redox mediator,
      such as 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonic acid] (ABTS) or 1
      hydroxybenzotriazole (HBT). However, laccase activity was considerably decreased
      in the presence of a redox mediator (ABTS or HBT). Further studies on
      identification of degradation byproducts and degradation pathways are
      recommended. 

PMID- 24034987
TI  - Decolorization and biodegradation of congo red dye by a novel white rot fungus
      Alternaria alternata CMERI F6.
AB  - A novel white rot fungus Alternaria alternata CMERI F6 decolorized 99.99% of 600
      mg/L congo red within 48 h in yeast extract-glucose medium at 25  degrees C, pH 5
      and 150 rpm. Physicochemical parameters like carbon and nitrogen sources,
      temperature, pH and aeration were optimized to develop faster decolorization
      process. Dye decolorization rate was maximal (20.21 mg/L h) at 25  degrees C, pH
      5, 150 rpm and 800 mg/L dye, giving 78% final decolorization efficiency. Scanning
      electron microscopy and X-ray Diffraction analysis revealed that the fungus
      become amorphous after dye adsorption. HPLC and FTIR analysis of the extracted
      metabolites suggested that the decolorization occurred through biosorption and
      biodegradation. Thermogravimetric analysis (TGA), differential thermal analysis
      (DTA) and acid-alkali and 70% ethanol treatment revealed the efficient dye
      retention capability of the fungus. The foregoing results justify the
      applicability of the strain in removal of congo red from textile wastewaters and
      their safe disposal.

PMID- 24034985
TI  - Chronic HIV disease and activation of the coagulation system.
AB  - With current effective antiretroviral treatment, the spectrum of morbidity and
      mortality during chronic HIV disease has shifted away from AIDS defining clinical
      events. Persistent abnormalities in coagulation appear to contribute to excess
      risk for a broad spectrum of non-AIDS defining complications, including, but not
      limited to, venous and arterial thrombotic disease. Mechanisms specific to HIV
      disease, antiretroviral therapy, and lifestyle or behavioral factors contribute
      to a pro-coagulant state, in part, through increased tissue factor activity
      coupled with a paradoxical decline in the anti-coagulant response. Alterations in
      coagulation biology in the context of HIV disease appear to be largely a
      consequence of persistent systemic immune activation, micro- and macro-vascular
      disease, and, potentially, impaired hepatic synthesis of coagulation factors. The
      clinical consequences of HIV-related changes in coagulation biology, the degree
      to which they are unique to HIV disease, and whether they can be mitigated
      through adjunct treatments, remains a focus of current research. 

PMID- 24034988
TI  - Indian medical students in public and private sector medical schools: are
      motivations and career aspirations different? - studies from Madhya Pradesh,
      India.
AB  - BACKGROUND: In recent years, there has been a massive growth in the private
      medical education sector in South Asia. India's large private medical education
      sector reflects the market driven growth in private medical education. Admission
      criteria to public medical schools are based on qualifying examination scores,
      while admission into private institutions is often dependent on relative academic
      merit, but also very much on the ability of the student to afford the education.
      This paper from Madhya Pradesh province in India aims to study and compare
      between first year medical students in public and private sector medical schools
      (i) motives for choosing a medical education (ii) career aspirations on
      completion of a medical degree (iii) willingness to work in a rural area in the
      short and long terms. METHODS: Cross sectional survey of 792 first year medical
      students in 5 public and 4 private medical schools in the province. RESULTS:
      There were no significant differences in the background characteristics of
      students in public and private medical schools. Reasons for entering medical
      education included personal ambition (23%), parental desire (23%),
      prestigious/secure profession (25%) or a service motive (20%). Most students
      wished to pursue a specialization (91%) and work in urban areas (64%) of the
      country. A small proportion (7%) wished to work abroad. There were no differences
      in motives or career aspirations between students of public or private schools.
      40% were willing to work in a rural area for 2 years after graduating; public
      school students were more willing to do so. CONCLUSION: There was little
      difference in background characteristics, motives for entering medicine or career
      aspirations between medical students in from public and private sector
      institutions.

PMID- 24034989
TI  - [Clinical pathway of primary lung cancer suegery (2013 edition)].

PMID- 24034990
TI  - [Trend analyses on the differences of lung cancer incidence between gender, area
      and average age in China during 1989-2008].
AB  - BACKGROUND AND OBJECTIVE: The lung cancer incidence was significantly increased
      in the past two decades in China. But the secular trend of lung cancer incidence
      difference between gender (male and female), area (urban and rural) and average
      age was not clear. The aim of this study is to analyze the trend of lung cancer
      incidence rate ratio between gender, area and average age in China during 1989
      2008, and provide some inspiration for lung cancer prevention and control
      activities. METHODS: Cancer registry data and population data in China from 1989
      to 2008 were collected by the National Cancer Registration Center. Stratified for
      gender and area, Poisson regression model was used to estimate annual lung cancer
      incidence rate ratio between male and female, urban and rural areas. The average
      age of lung cancer incidence was calculated. Linear regression was used to model
      the trend of annual incidence rate ratio and average age over time. RESULTS:
      Incidence rate ratios of lung cancer between male and female, urban and rural
      areas were significantly decreased from 2.47 and 2.07 to 2.28 and 1.14 during
      1989-2008, respectively. Meanwhile, the average age of lung cancer incidence
      among male and female dramatically increased from 65.32 and 65.14 to 67.87 and
      68.05, respectively. CONCLUSIONS: The difference of lung cancer incidence between
      male and female, urban and rural areas remarkably decreased from 1989 to 2008.
      The average age of lung cancer occurrence gradually increased. Researches,
      prevention and control activities on lung cancer with consideration of new
      incidence pattern should be strengthened.

PMID- 24034991
TI  - [Establishing the nude mice bone metastasis model of lung adenocarcinoma and
      applying MicroCT into the observation].
AB  - BACKGROUND AND OBJECTIVE: 50%-70% of patients with advanced lung cancer will
      develop bone metastases. The aim of this study is to establish the nude mice bone
      metastasis model of lung adenocarcinoma using A549, H1299, SPC-A-1 and XL-2, all
      of which own different invasion and migration abilities in vitro and supervise
      the bone metastases by MicroCT. METHODS: fifty BALB/C-nu/nu nude mice were
      grouped into five groups on average randomly. Cells of the four cell lines were
      injected into the left cardiac ventricle of mice in the four experimental groups
      (0.2 mL/mouse) respectively; meanwhile, mice in the control group were injected
      with normal saline (0.2 mL/mouse) in the same manner. Periodical radiological
      examination was carried out to supervise the variation of the mice since the
      second week after injection. When mice in each group became thin obviously, end
      the experiment of this group. Before the end, pathological sections of bone
      tissues were made. We classified the bone metastatic sites into axial skeleton
      and limb bone, in order to compare the metastatic rates of these two different
      parts. The bone metastatic abilities of the four cell lines was statistically
      analyzed by comparing the average time cost in the appearance of bone metastases
      and the percentage of bone metastases among the experimental groups. RESULTS:
      Different metastatic sites which had been identified both by MicroCT and
      pathological sections appeared in each group of the four experimental groups. By
      contrast, no metastasis was observed in the control group. The percentage of
      cancer metastasizing to axial skeleton was remarkably higher than the percentage
      of tumor metastasizing to the limb bone in each experimental group, which was
      consistent with the clinical regularity and characteristics of skeletal
      metastases with lung cancer. Thus, the model has been established triumphantly.
      However, there were no statistical differences in the average time consumed and
      skeletal metastatic rate among the four experimental groups. CONCLUSIONS: The
      disruption in the bone can be clearly detected by MicroCT, which is benefit to
      supervise the osseous metastasis. We successfully developed the nude mice bone
      metastasis model of lung adenocarcinoma, which will pave the way for exploring
      novel prevention and therapy strategies clinically. The four cell lines varied in
      invasion and migration abilities in vitro, but there was no statistical
      difference in the metastatic ability in vivo, and the reason need to be explored
      further in future.

PMID- 24034992
TI  - [Metronomic chemotherapy combined with dendritic cell vaccine ?inhibits VEGF
      secretion].
AB  - BACKGROUND AND OBJECTIVE: The survival rate of lung cancer is low, thus new
      methods for treating this form of cancer must be explored. This study applies
      immune therapy with metronomic chemotherapy to observe the effect of combined
      therapy on suppressing tumor. METHODS: Mice were inoculated with Lewis lung
      carcinoma cells. Different treatments, namely, saline, metronomic chemotherapy,
      dendritic cell (DC) vaccine, and metronomic chemotherapy with DC vaccine were
      administered to corresponding mice groups. Basic fibroblast growth factor and
      vascular endothelial growth factor (VEGF) were detected via microdialysis and
      Luminex. RESULTS: The median survival time of mice in the metronomic chemotherapy
      with DC vaccine group was (27.6+/-3.2) days, whereas that in the saline group was
      (13.5+/-2.7) days (P=0.008), that in the DC) vaccine group was (13.1+/-2.3) days
      (P=0.01), and that in the metronomic chemotherapy group was (11.8+/-3.0) days
      (P=0.01). The mice in the metronomic chemotherapy with DC vaccine group exhibited
      longer survival time than the mice in the other groups. This result could be
      related to the downregulation of VEGF secretion in the tumor-bearing mice groups
      within 48 h to 72 h. CONCLUSIONS: VEGF secretion could be downregulated in tumor
      bearing mice by administering metronomic chemotherapy with DC vaccine.

PMID- 24034993
TI  - [c-Met signaling pathway participating in the gefitinib resistance of different
      gene types of non-small cell lung cancer cells induced by HGF in vitro].
AB  - BACKGROUND AND OBJECTIVE: It has been known that hepatocyte growth factor (HGF)
      induces gefitinib resistance in non-small cell lung cancer (NSCLC) cells. The
      possible mechanism may be related to the activation of the HGF receptor c-Met.
      The aim of this study is to investigate the involvement of c-Met and its
      downstream signaling pathway in the HGF-induced gefitinib resistance of NSCLC
      cells with different epidermal growth factor receptor (EGFR) gene types. METHODS:
      NSCLC cell lines with different EGFR genes (PC-9, PC9/R, H292, and A549) were
      selected and induced by HGF. Cell survival was determined by MTT assay and the
      expression of Met and downstream signaling proteins were examined by Western
      blot. RESULTS: Gefitinib inhibited the cell growth of PC9, H292, and A549 cell
      lines in a dose-dependent manner. The concentration-survival curve notably
      shifted to the right when induced by HGF. The apoptotic rate was lower when the
      cells were treated with HGF and gefitinib than when these cells were treated with
      gefitinib alone (P<0.05), particularly in PC9, H292, and A549 cells, but not in
      PC9/R. HGF stimulated the phosphorylation of Met and downstream signaling
      proteins in PC9, H292, PC9/R, and A549 cell lines. p-Met, p-Akt, p-Stat3, and p
      Erk1/2 expressions were higher when the cells were treated with HGF and gefitinib
      than when these cells were treated with gefitinib alone, particularly in PC9,
      H292, and A549 cells, but not in PC9/R. CONCLUSIONS: c-Met and its downstream
      signaling pathway possibly participated in the HGF-induced gefitinib resistance
      in NSCLC cells with different EGFR gene types.

PMID- 24034994
TI  - [A retrospective study of the efficacy and toxicity of irinotecan in combination
      with nedaplatin versus irinotecan in combination with cisplatin as
      salvage?treatment in refractory or relapsed small cell lung cancer].
AB  - BACKGROUND AND OBJECTIVE: At present no standard second-line combination has been
      established for recurrent small cell lung cancer (SCLC). Therefore we evaluate
      the efficacy and safety of irinotecan in combination with nedaplatin/cisplatin
      against refractory or relapsed small cell lung cancer. METHODS: In this
      retrospective study, we analyzed the data of 1,140 patients who diagnosed small
      cell lung cancer at our hospital from April 2009 to April 2012. Of all the
      patients, 34 patients were treated with irinotecan and nedaplatin (irinotecan 60
      mg/m2 on days 1, 8 nedaplatin 85 mg/m2 day 1, every 3 weeks) , and 20 patients
      were treated with irinotecan and cisplatin (irinotecan 60 mg/m2 on days 1, 8
      cisplatin 75 mg/m2 day 1, every 3 weeks) as the second-line treatment. Prognostic
      factors of overall survival (OS) were estimated by Kaplan-Meier and Cox's
      Regression-proportional hazards model. RESULTS: Of all the 54 eligible patients,
      median progression free survival (PFS) was 4.9 months, and median OS was 13.3
      months. Median PFS was 5.4 months for irinotecan plus nedaplatin (IN) and 4.9
      months for irinotecan plus cisplatin (IC), respectively (P=0.465). Median OS was
      14.3 months and 13.3 months, respectively (P=0.704). In multivariate analysis,
      ECOG PS, number of metastases and cycles of chemotherapy were independent
      prognostic factors. The toxicities were mild, while toxicity profile was slightly
      different for each of the arms: hematologic toxicity was higher in IN group, and
      diarrhea was higher in IC group. CONCLUSIONS: Irinotecan plus platinum is
      effective and tolerable for refractory and relapsed small cell lung cancer.
      Irinotecan plus nedaplatin is non-inferior to irinotecan plus cisplatin in terms
      of efficacy and safety.

PMID- 24034995
TI  - [Th17 cells and IL-17 are increased in patients with brain metastases from the
      primary lung cancer].
AB  - BACKGROUND AND OBJECTIVE: Th17 cells are important T helper cells, which are
      characterized by their production of IL-17. Th17 cells play an important role in
      host defense against microbial infections, autoimmune diseases and cancer. The
      aim of this study is to investigate the percentage of Th17 in peripheral blood
      lymphocyte and the level of IL-17 in serum and cerebrospinal fluid (CSF) in
      patients with brain metastases from lung cancer. METHODS: Twenty-two patients
      with brain metastases from lung cancer and 20 health controls were analyzed. The
      percentage of Th17 cell was detected with flow cytometry using CD3+CD4+IL-23R+
      marker, the level of IL-17 was measured with ELISA method. RESULTS: The
      percentage of Th17 cells in patients with brain metastases from lung cancer was
      4.65%+/-0.72%, which was remarkably higher than that in controls (2.71%+/-0.54%,
      P=0.04). There was no significant difference between non-small cell lung cancer
      (NSCLC) patients and small cell lung cancer (SCLC) patients. Serum IL-17 was
      remarkably increased in patients with brain metastases from lung cancer (117.4+/
      16.43 pg/mL vs 72.55+/-8.19 pg/mL, P=0.02). No significant difference of the
      serum IL-17 was observed between NSCLC and SCLC patients. The level of IL-17 in
      CSF from patients with brain metastases from lung cancer was significant higher
      than that from lung cancer patients without brain metastases (73.21+/-7.52 pg/mL
      vs 50.25+/-8.04 pg/mL, P=0.04). CONCLUSIONS: Th17 cells and IL-17 increase in
      patients with brain metastases from lung cancer. It may involve in the
      pathogenesis of brain metastases from lung cancer.

PMID- 24034996
TI  - [Clinical application of endobronchial ultrasound-guided transbronchial needle
      ?aspiration biopsy for the diagnosis of superior vena cava obstruction syndrome].
AB  - BACKGROUND AND OBJECTIVE: Mediastinal lymphoma or right upper lung cancer is a
      common cause of superior vena cava obstruction syndrome (SVCOS). Endobronchial
      ultrasound-guided needle aspiration (EBUS-TBNA) biopsy is applied for the
      diagnosis of mediastinal mass disease. The aim of this study is to explore the
      safety and feasibility of EBUS-TBNA biopsy under general anesthesia for the
      clinical diagnosis of SVCOS. METHODS: Twenty-five cases of SVCOS received EBUS
      TBNA under general anesthesia between June 2012 and June 2013. The group
      consisted of 16 male and 9 female patients aged 33 years to 76 years, with a
      median age of 62.5. RESULTS: Twenty-four cases were confirmed to be of malignant
      pathology, and one case failed to yield a clear pathological diagnosis. No
      patient experienced any complications related to the operation, such as heavy
      bleeding and pneumothorax. CONCLUSIONS: For patients presenting with SVCOS, EBUS
      TBNA under general anesthesia is a safe and reliable inspection method of high
      diagnostic yield. This method can be used for routine examination when other
      means cannot obtain clear pathological diagnosis.

PMID- 24034997
TI  - [Clinical analysis of thoracoscopic lobectomy in the treatment of peripheral lung
      cancer with single utility port].
AB  - BACKGROUND AND OBJECTIVE: Video-assisted thoracoscopic surgery (VATS) lobectomy
      is now generally accepted for patients with lung cancer. The aim of this study is
      to review the technology of thoracoscopic lobectomy with single utility port in
      the treatment of peripheral lung cancer. METHODS: We retrospectively analyzed the
      clinical data of 87 patients with peripheral lung cancer who underwent single
      utility port complete VATS lobectomy from February 2011 to January 2013 in the
      First Affiliated Hospital of Soochow University (single utility port group), and
      compared them with 75 patients with peripheral lung cancer who underwent
      conventional, 3-port VATS lobectomy in the same period (3-port group). The
      clinical outcomes including operation time, time to first activity out of bed,
      postoperative hospital stay, intraoperative blood loss, postoperative drainage
      volume, chest drainage duration, lymph node dissection number, postoperative
      complications and degree of chest pain were compared between the two groups.
      RESULTS: No perioperative death was observed in both groups. There was no
      statistical difference in operation time (151.03+/-25.97 min vs 156.27+/-26.49
      min), lymph node dissection number (13.06+/-1.36 vs 12.61+/-1.56), intraoperative
      blood loss (188.62+/-47.03 mL vs 179.60+/-28.96 mL) and incidence of serious
      postoperative complications (18/87 vs 21/75) between the two groups. There were
      statistical differences in time to first activity out of bed (11.17+/-8.69 h vs
      13.76+/-7.43 h), postoperative hospital stay (7.18+/-1.95 d vs 7.92+/-2.03 d),
      chest drainage duration (3.85+/-1.21 d vs 4.43+/-1.43 d) and total postoperative
      drainage volume (671.49+/-178.31 mL vs 736.93+/-170.39 mL) between the two groups
      (P<0.05). The change of vision analogue score (VAS) score between the two groups
      after operation was also statistically significant (P<0.01). CONCLUSIONS: The
      completely thoracoscopic lobectomy with single utility port is a safe and
      feasible surgical procedure compared with conventional 3-port VATS lobectomy for
      selected patients.

PMID- 24034998
TI  - [The prognostic value of micrometastasis in non-small cell lung cancer].
AB  - Lung cancer ranks top in morbidity and mortality among the malignancies in China.
      Non-small cell lung cancer (NSCLC) accounts for about 80%-85% of all lung
      malignancies. The stage at diagnosis is the principal prognostic indicator, and
      accurate staging is essential for treatment decisions. After radical surgical
      resection in patients with stage I disease, the recurrence rate ranges from 25%
      to 30%. Patients with a poor outcome may have occult locoregional and/or distant
      metastasis before resection. In recent years, there are a lot of researches
      aimingat detecting micrometastasis and evaluating the prognostic value of it.
      This study reviewed the prognostic value of micrometastasis in lymph node, bone
      marrow, pleural cavity and peripheral blood. 

PMID- 24035000
TI  - Does sex matter? Differential responses to corticosterone administration in the
      zebra finch.
AB  - Because of potentially deleterious effects of chronic stress, physiological
      measurements of stress hormones (in birds, corticosterone (CORT)) are often used
      to determine the consequences of natural or human-induced change. Often, it is
      assumed that CORT levels will be similar between the sexes and the results are
      pooled. However, recent studies have reported sex differences in CORT
      concentrations in avian species. As zebra finches (Taeniopygia guttata) are one
      of the most widely used bird species in laboratory studies worldwide, potential
      sex-specific differences in hormone metabolism, as well as the clearance rate of
      oral doses of exogenous CORT, are highly relevant. The results of this study show
      that female zebra finches have a significantly higher baseline CORT than males,
      which could partially be a product of differential responses to semi-isolation.
      In addition, a single dose of exogenous CORT resulted in different blood profiles
      between the sexes over time, though exogenous CORT was cleared from blood within
      90 min following treatment in both sexes. Interestingly, exposure to multiple
      doses of exogenous CORT resulted in elevated CORT levels 24h after treatment in
      both sexes. These results highlight the need for further investigations into
      potential sex differences in hormone metabolism, as well as possible cumulative
      effects of repeated stress.

PMID- 24034999
TI  - [Diagnosis and management of solitary pulmonary nodules].
AB  - Currently in China, the incidence and death rate of lung cancer with low five
      year survival rates has ranked the first position among all cancers. Early
      detection of lung cancer and early treatment are of great importance. However,
      patients with early satge lung cancer always do not present with any synptoms or
      signs, only to demonstrate solitary pulmonary nodules (SPNs) in radiology
      findings. So it is very critical to improve the ability to identify the SPNs, and
      with the development of sorts of diagnostic modalities, the accuracy in the
      evaluation of the SPNs has imporved greatly. 

PMID- 24035001
TI  - Responses of melanocytes and melanomacrophages of Eupemphix nattereri (Anura:
      Leiuperidae) to Nle4, D-Phe7-alpha-melanocyte stimulating hormone and
      lipopolysaccharides.
AB  - Melanocytes are found in various organs of ectothermic animals, playing a
      protective role against bacteria and free radicals. It is known that pigment
      cells from hematopoietic organs have immune functions. However, the role of
      visceral melanocytes is not well understood. Cutaneous melanocytes are responsive
      to alpha-melanocyte stimulating hormone (alpha-MSH), which is associated with the
      dispersion of melanin granules within melanocytes. alpha-MSH has also been
      reported to inhibit most forms of inflammatory responses by decreasing the pro
      inflammatory cytokines and neutrophil migration. The present study evaluated the
      influence of an alpha-MSH analog (Nle(4), D-Phe(7)-alpha-MSH) and
      lipopolysaccharides (LPS) from Escherichia coli on the liver and testicular
      tissues of the anuran Eupemphix nattereri. The tested hypotheses were: (i) the
      pigmented area will increase following hormone and LPS administration, (ii) pre
      treatment with alpha-MSH will decrease the number of mast cells, and (iii) the
      hormone will have protective effects against LPS-induced responses. We found that
      hormone administration did not change hepatic pigmentation, but increased
      testicular pigmentation. Testicular pigmentation quickly increased after LPS
      administration, whereas there was a late response in the liver. The response of
      enhanced pigmentation was delayed and the number of mast cells decreased in
      animals previously treated with the alpha-MSH analog when compared to the LPS
      group. Hemosiderin and lipofuscin were found in melanomacrophages, but not in
      testicular melanocytes. Although both the liver and the testes of E. nattereri
      have pigmented cells, these are distinct in morphology, embryonic origin, and
      pigmentary substances. These differences may be responsible for the different
      responses of these cells to the alpha-MSH analog and LPS administration.

PMID- 24035002
TI  - Burden reduction of caregivers for users of care services provided by the public
      long-term care insurance system in Japan.
AB  - We surveyed the care burden of family caregivers, their satisfaction with the
      services, and whether their care burden was reduced by the introduction of the
      LTCI care services. We randomly enrolled 3000 of 43,250 residents of Nagoya City
      aged 65 and over who had been certified as requiring long-term care and who used
      at least one type of service provided by the public LTCI; 1835 (61.2%) subjects
      returned the survey. A total of 1015 subjects for whom complete sets of data were
      available were employed for statistical analysis. Analysis of variance for the
      continuous variables and chi(2) analysis for that categorical variance were
      performed. Multiple logistic analysis was performed with the factors with p
      values of <0.2 in the chi(2) analysis of burden reduction. A total of 68.8% of
      the caregivers indicated that the care burden was reduced by the introduction of
      the LTCI care services, and 86.8% of the caregivers were satisfied with the LTCI
      care services. A lower age of caregivers, a more advanced need classification
      level, and more satisfaction with the services were independently associated with
      a reduction of the care burden. In Japanese LTCI, the overall satisfaction of the
      caregivers appears to be relatively high and is associated with the reduction of
      the care burden. 

PMID- 24035003
TI  - Broadband inversion of 1J(CC) responses in 1,n-ADEQUATE spectra.
AB  - Establishing the carbon skeleton of a molecule greatly facilitates the process of
      structure elucidation, both manual and computer-assisted. Recent advances in the
      family of ADEQUATE experiments demonstrated their potential in this regard. 1,1
      ADEQUATE, which provides direct (13)C-(13)C correlation via (1)J(CC), and 1,n
      ADEQUATE, which typically yields (3)J(CC) and (1)J(CC) correlations, are more
      sensitive and more widely applicable experiments than INADEQUATE and PANACEA. A
      recently reported modified pulse sequence that semi-selectively inverts (1)J(CC)
      correlations in 1,n-ADEQUATE spectra provided a significant improvement, allowing
      (1)J(CC) and (n)J(CC) correlations to be discerned in the same spectrum. However,
      the reported experiment requires a careful matching of the amplitude transfer
      function with (1)J(CC) coupling constants in order to achieve the inversion, and
      even then some (1)J(CC) correlations could still have positive intensity due to
      the oscillatory nature of the transfer function. Both shortcomings limit the
      practicality of the method. We now report a new, dual-optimized inverted (1)J(CC)
      1,n-ADEQUATE experiment, which provides more uniform inversion of (1)J(CC)
      correlations across the range of 29-82 Hz. Unlike the original method, the dual
      optimization experiment does not require fine-tuning for the molecule's (1)J(CC)
      coupling constant values. Even more usefully, the dual-optimized version provides
      up to two-fold improvement in signal-to-noise for some long-range correlations.
      Using modern, cryogenically-cooled probes, the experiment can be successfully
      applied to samples of ~1 mg under favorable circumstances. The improvements
      afforded by dual optimization inverted (1)J(CC) 1,n-ADEQUATE experiment make it a
      useful and practical tool for NMR structure elucidation and should facilitate the
      implementation and utilization of the experiment.

PMID- 24035004
TI  - Stabilization of the inverse Laplace transform of multiexponential decay through
      introduction of a second dimension.
AB  - We propose a new approach to stabilizing the inverse Laplace transform of a
      multiexponential decay signal, a classically ill-posed problem, in the context of
      nuclear magnetic resonance relaxometry. The method is based on extension to a
      second, indirectly detected, dimension, that is, use of the established framework
      of two-dimensional relaxometry, followed by projection onto the desired axis.
      Numerical results for signals comprised of discrete T1 and T2 relaxation
      components and experiments performed on agarose gel phantoms are presented. We
      find markedly improved accuracy, and stability with respect to noise, as well as
      insensitivity to regularization in quantifying underlying relaxation components
      through use of the two-dimensional as compared to the one-dimensional inverse
      Laplace transform. This improvement is demonstrated separately for two different
      inversion algorithms, non-negative least squares and non-linear least squares, to
      indicate the generalizability of this approach. These results may have wide
      applicability in approaches to the Fredholm integral equation of the first kind. 

PMID- 24035005
TI  - Henry N. Wagner, Jr.

PMID- 24035006
TI  - The next accreditation system in radiology: a report from the APDR residency
      structure committee.
AB  - In a move to emphasize the educational outcomes of training programs, the ACGME
      has created the Next Accreditation System (NAS). The stated goals of NAS include
      aiding the ACGME in the accreditation of programs based on educational outcome
      measures, decreasing program burdens associated with the conventional process
      based approach to ACGME accreditation, allowing good programs to innovate while
      enabling struggling programs to steadily improve, and providing public
      accountability for outcomes. Diagnostic radiology is among the first group of
      specialties to undergo NAS implementation and began operating under the NAS in
      July 2013. This article describes the various components of the NAS and explains
      the new elements, including the clinical learning environment review program, the
      milestones, the clinical competency committee, and the self-study visits. 

PMID- 24035007
TI  - Addressing unmet need for long-acting family planning in Ethiopia: uptake of
      single-rod progestogen contraceptive implants (Implanon) and characteristics of
      users.
AB  - OBJECTIVE: To describe women who accept single-rod progestogen contraceptive
      implants (Implanon; N.V. Organon, Oss, Netherlands) from community health workers
      in Ethiopia and to assess whether community-based provision addresses unmet need
      for contraception. METHODS: Women who accepted Implanon during training events in
      4 regions were asked about their characteristics and use of family planning. They
      were compared with implant users nationally and women with unmet need in the
      Ethiopia Demographic and Health Survey (DHS). Differences between groups were
      tested using 2-sample comparisons of proportions and means. RESULTS: On average,
      Implanon acceptors were younger and had more years of education and fewer
      children than implant users nationally. Almost one-quarter (22.9%) of all
      participants had never used contraception before; this was slightly higher among
      women who chose Implanon (23.1% vs 16.4%; P=0.04). Acceptors were also less
      likely than non-acceptors to be using contraception (70.8% vs 77.3%; P<0.05) but
      all women interviewed were more likely to be using contraception than the rural
      population. Women who accepted Implanon were younger but more educated than women
      with unmet need for contraception in the 2005 DHS. CONCLUSION: Provision of
      Implanon at the community level through community health workers is effective in
      reaching women with the greatest need for contraception.

PMID- 24035008
TI  - Mitochondrial carrier homolog 1 (Mtch1) antibodies in neuro-Behcet's disease.
AB  - Efforts for the identification of diagnostic autoantibodies for neuro-Behcet's
      disease (NBD) have failed. Screening of NBD patients' sera with protein
      macroarray identified mitochondrial carrier homolog 1 (Mtch1), an apoptosis
      related protein, as a potential autoantigen. ELISA studies showed serum Mtch1
      antibodies in 68 of 144 BD patients with or without neurological involvement and
      in 4 of 168 controls corresponding to a sensitivity of 47.2% and specificity of
      97.6%. Mtch1 antibody positive NBD patients had more attacks, increased
      disability and lower serum nucleosome levels. Mtch1 antibody might be involved in
      pathogenic mechanisms of NBD rather than being a coincidental byproduct of
      autoinflammation. 

PMID- 24035009
TI  - Nimodipine in the current era of subarachnoid hemorrhage management: standard of
      care or primed for a definitive randomized trial?

PMID- 24035010
TI  - Cuts drive health system reforms in Spain.
AB  - The economic crisis is largely shaping health policy in Spain. This paper reports
      on major changes in the health care system, both nationally and regionally, as a
      consequence of sizable cutbacks and new pieces of legislation. The most relevant
      changes to the system introduced during the last year are having an impact on who
      is insured, which benefits are covered, and what share of the cost of service
      provision is contributed by the population, while at the same time reducing
      salaries and working conditions in the sector. We further report on the
      consequences these changes are having, and the roles played by key actors and
      organisations in the system. 

PMID- 24035012
TI  - Biosciences within the pre-registration (pre-requisite) curriculum: an
      integrative literature review of curriculum interventions 1990-2012.
AB  - BACKGROUND: The learning of biosciences is well-documented to be problematic as
      students find the subjects amongst the most difficult and anxiety-provoking of
      their pre-registration programme. Studies suggest that learning consequently is
      not at the level anticipated by the profession. Curriculum innovations might
      improve the situation but the effectiveness of applied interventions has not been
      evaluated. OBJECTIVE: To undertake an integrative review and narrative synthesis
      of curriculum interventions and evaluate their effect on the learning of
      biosciences by pre-registration student nurses. Review methods A systematic
      search of electronic databases CINAHL, Medline, British Nursing Index and Google
      Scholar for empirical research studies was designed to evaluate the introduction
      of a curriculum intervention related to the biosciences, published in 1990-2012.
      Studies were evaluated for design, receptivity of the intervention and impact on
      bioscience learning. RESULTS: The search generated fourteen papers that met
      inclusion criteria. Seven studies introduced on-line learning packages, five an
      active learning format into classroom teaching or practical sessions, and two
      applied Audience Response Technology as an exercise in self-testing and
      reflection. Almost all studies reported a high level of student satisfaction,
      though in some there were access/utilization issues for students using on-line
      learning. Self-reporting suggested positive experiences, but objective evaluation
      suggests that impacts on learning were variable and unconvincing even where an
      effect on course progress was identified. Adjunct on-line programmes also show
      promise for supporting basic science or language acquisition. CONCLUSIONS:
      Published studies of curriculum interventions, including on-line support, have
      focused too heavily on the perceived benefit to students rather than objective
      measures of impact on actual learning. Future studies should include rigorous
      assessment evaluations within their design if interventions are to be adopted to
      reduce the 'bioscience problem'.

PMID- 24035011
TI  - Reprogramming human fibroblasts to neurons by recapitulating an essential
      microRNA-chromatin switch.
AB  - The development of the vertebrate nervous system requires a switch of ATP
      dependent chromatin remodeling mechanisms, which occurs by substituting subunits
      within these complexes near cell cycle exit. This switching involves a triple
      negative genetic circuitry in which REST represses miR-9 and miR-124, which in
      turn repress BAF53a, which in turn repress the homologous neuron-specific BAF53b.
      Recapitulation of this microRNA/chromatin switch in human fibroblasts converts
      them to neurons. The genes involved in this fate-determining chromatin switch
      play genetically dominant roles in several human neurologic diseases suggesting
      that they are rate-limiting for aspects of human neural development. We review
      how this switch in ATP-dependent chromatin complexes might interface with
      traditional ideas about neural determination and reprogramming. 

PMID- 24035013
TI  - Acute effects of incremental inspiratory loads on compartmental chest wall volume
      and predominant activity frequency of inspiratory muscle.
AB  - AIM: This research aims to analyze the acute effect of incremental inspiratory
      loads on respiratory pattern and on the predominant activity frequency of
      inspiratory muscle, taking into account differences in gender responses.
      Optoelectronic Plethysmography was performed during loads in 39 healthy subjects
      (20 women), placing 89 markers on the thoracic-abdominal wall to obtain total and
      regional volumes. Surface electromyography (SEMG) was taken simultaneously on the
      Sternocleidomastoid and Diaphragm muscles, to calculate the predominant muscle
      activity frequency through wavelet analysis. Inspiratory loads were performed
      using Threshold((r))with 2 min of breathing at different levels, ranging from a
      load of 10 cmH(2)O plus 5 cmH(2)O to 40 cmH(2)O or fatigue. RESULTS: Inspiratory
      Time increased during loads. Total and compartmental volumes increased with
      different regions, changing at different loads. These changes in volume occur
      earlier in women (20 cmH(2)O) than in men (30 cmH(2)O). The predominant activity
      frequency of Sternocleidmastoid muscle decreased at 30 cmH(2)O, while Diaphragm
      activity decreased at 40 cmH(2)O. CONCLUSION: The acute effects of incremental
      inspiratory loads are increases of total and regional volumes and inspiratory
      time. As for muscle activity, the predominant activity frequency declined in
      Sternocleidomastoid and Diaphragm muscles, but at different loads. Such
      respiratory and SEMG patterns and gender differences should be considered when
      clinical interventions are performed.

PMID- 24035014
TI  - Applied osmotic loading for promoting development of engineered cartilage.
AB  - This study investigated the potential use of static osmotic loading as a
      cartilage tissue engineering strategy for growing clinically relevant grafts from
      either synovium-derived stem cells (SDSCs) or chondrocytes. Bovine SDSCs and
      chondrocytes were individually encapsulated in 2% w/v agarose and divided into
      chondrogenic media of osmolarities 300 (hypotonic), 330 (isotonic), and 400
      (hypertonic, physiologic) mOsM for up to 7 weeks. The application of hypertonic
      media to constructs comprised of SDSCs or chondrocytes led to increased
      mechanical properties as compared to hypotonic (300mOsM) or isotonic (330mOsM)
      media (p<0.05). Constant exposure of SDSC-seeded constructs to 400mOsM media from
      day 0 to day 49 yielded a Young's modulus of 513+/-89kPa and GAG content of
      7.39+/-0.52%ww on day 49, well within the range of values of native, immature
      bovine cartilage. Primary chondrocyte-seeded constructs achieved almost as high a
      Young's modulus, reaching 487+/-187kPa and 6.77+/-0.54%ww (GAG) for the 400mOsM
      condition (day 42). These findings suggest hypertonic loading as a
      straightforward strategy for 3D cultivation with significant benefits for
      cartilage tissue engineering strategies. In an effort to understand potential
      mechanisms responsible for the observed response, cell volume measurements in
      response to varying osmotic conditions were evaluated in relation to the Boyle
      van't Hoff (BVH) law. Results confirmed that chondrocytes behave as perfect
      osmometers; however SDSCs deviated from the BVH relation. 

PMID- 24035015
TI  - Simulation of upper airway occlusion without and with mandibular advancement in
      obstructive sleep apnea using fluid-structure interaction.
AB  - Obstructive Sleep Apnea (OSA) is a common sleep disorder characterized by
      repetitive collapse of the upper airway (UA). One treatment option is a
      mandibular advancement splint (MAS) which protrudes the lower jaw, stabilizing
      the airway. However not all patients respond to MAS therapy and individual
      effects are not well understood. Simulations of airway behavior may represent a
      non-invasive means to understand OSA and individual treatment responses. Our aims
      were (1) to analyze UA occlusion and flow dynamics in OSA using the fluid
      structure interaction (FSI) method, and (2) to observe changes with MAS. Magnetic
      resonance imaging (MRI) scans were obtained at baseline and with MAS in a known
      treatment responder. Computational models of the patients' UA geometry were
      reconstructed for both conditions. The FSI model demonstrated full collapse of
      the UA (maximum 5.83mm) pre-treatment (without MAS). The UA collapse was located
      at the oropharynx with low oropharyngeal pressure (-51.18Pa to -39.08Pa) induced
      by velopharyngeal jet flow (maximum 10.0m/s). By comparison, simulation results
      from the UA with MAS, showed smaller deformation (maximum 2.03mm), matching the
      known clinical response. Our FSI modeling method was validated by physical
      experiment on a 1:1 flexible UA model fabricated using 3D steriolithography. This
      is the first study of airflow dynamics in a deformable UA structure and
      inspiratory flow. These results expand on previous UA models using computational
      fluid dynamics (CFD), and lay a platform for application of computational models
      to study biomechanical properties of the UA in the pathogenesis and treatment of
      OSA. 

PMID- 24035016
TI  - Factors affecting energy and nitrogen efficiency of dairy cows: a meta-analysis.
AB  - A meta-analysis was performed to explore the correlation between energy and
      nitrogen efficiency of dairy cows, and to study nutritional and animal factors
      that influence these efficiencies, as well as their relationship. Treatment mean
      values were extracted from 68 peer-reviewed studies, including 306 feeding
      trials. The main criterion for inclusion of a study in the meta-analysis was that
      it reported, or permitted calculation of, energy efficiency (Eeff; energy in
      milk/digestible energy intake) and nitrogen efficiency (Neff; nitrogen in
      milk/digestible nitrogen intake) at the digestible level (digestible energy or
      digestible protein). The effect of nutritional and animal variables, including
      neutral detergent fiber, acid detergent fiber (ADF), digestible energy,
      digestible protein, proportion of concentrate (PCO), dry matter intake, milk
      yield, days in milk, and body weight, on Eeff, Neff, and the Neff:Eeff ratio was
      analyzed using mixed models. The interstudy correlation between Eeff and Neff was
      0.62, whereas the intrastudy correlation was 0.30. The higher interstudy
      correlation was partly due to milk yield and dry matter intake being present in
      both Eeff and Neff. We, therefore, also explored the Neff:Eeff ratio. Energy
      efficiency was negatively associated with ADF and PCO, whereas Neff was
      negatively associated with ADF and digestible energy. The Neff:Eeff ratio was
      affected by ADF and PCO only. In conclusion, the results indicate a possibility
      to maximize feed efficiency in terms of both energy and nitrogen at the same
      time. In other words, an improvement in Eeff would also mean an improvement in
      Neff. The current study also shows that these types of transverse data are not
      sufficient to study the effect of animal factors, such as days in milk, on feed
      efficiency. Longitudinal measurements per animal would probably be more
      appropriate. 

PMID- 24035017
TI  - Plane of nutrition during the preweaning period but not the grower phase
      influences the neutrophil activity of Holstein calves.
AB  - Two experiments were conducted to determine the influence of plane of nutrition
      during (1) the pre- and immediate postweaning periods and (2) the grower phase on
      the performance and leukocyte responses of Holstein calves. In experiment 1, 39
      (2 +/- 1 d old) colostrum-fed heifer calves were randomly assigned to 2 planes of
      nutrition, a low (LPN; n = 19) and a high plane of nutrition (HPN; n = 20).
      Calves in the LPN treatment were offered 418 g/d of dry matter (DM) of a 20%
      crude protein (CP)/20% fat milk replacer, whereas calves in the HPN treatment
      were offered 747 and 1,010 g/d of DM of a 28% CP/20% fat milk replacer during wk
      1 and wk 2 to 6, respectively. Calves were offered ad libitum access to a calf
      starter until the end of the study. Peripheral blood samples were collected on d
      3, 10, 21, 45, 47, 53, and 91 for many ex vivo leukocyte responses and
      biochemical analyses. A nutrition * time interaction was present for average
      daily gain and feed efficiency (feed:gain ratio). A nutrition * time interaction
      existed for plasma glucose concentration. Neutrophil L-selectin expression was
      greater in calves fed the LPN than HPN on d 3 and 21. The percentage of
      neutrophils producing an oxidative burst (OB) when cocultured with Escherichia
      coli tended to be greater and was greater in calves fed the LPN than HPN on d 10
      and 21, respectively. In addition, neutrophils from calves fed the LPN had
      greater OB intensity throughout the neonatal period (0 to 21 d). However, plasma
      haptoglobin was not different between the 2 planes of nutrition throughout the
      study. In experiment 2, 50 heifer calves that were all previously fed a HPN
      similar to that described for experiment 1 were randomly assigned to 2 planes of
      nutrition (HPN and LPN) during the grower phase (5 pens/treatment; 5 calves/pen).
      Calves fed the HPN during the grower phase were fed 4.1 kg of concentrate DM
      (pellets; 22.4% CP, DM basis) per head per day, whereas calves on the LPN during
      the grower phase were fed 1.6 kg of DM of the same concentrate per head per day.
      All calves were fed alfalfa hay (16.2% CP; DM basis) ad libitum. Overall, average
      daily gain was greater in HPN calves than LPN calves. No differences were noticed
      for concentrations of plasma urea nitrogen, glucose, neutrophil L-selectin
      expression, percentage of neutrophils producing OB, and plasma haptoglobin
      concentration between the 2 planes of nutrition. In summary, intake and
      performance were improved in calves fed the HPN than calves fed the LPN in both
      experiments. The neutrophil responses of calves fed an LPN were more active
      during the preweaning period than calves fed an HPN; however, this response was
      not observed during the immediate postweaning period or the grower phase.

PMID- 24035018
TI  - Effect of feed presentation on feeding patterns of dairy calves.
AB  - The objectives of this study were to determine the effect of feed presentation on
      meal frequency and duration, as well as diurnal feeding patterns of dairy calves,
      and to assess any longer-term differences in feeding patterns resulting from
      previous experience. Twenty Holstein bull calves were exposed from wk 1 to 8 of
      life to 1 of 2 feed presentation treatments: concentrate and chopped grass hay
      (<2.5 cm) offered at a ratio of 7:3 as a mixture (MIX), or as separate components
      (COM). Feed was provided ad libitum. Calves received 8L/d of milk replacer (1.2
      kg of dry matter), with the amount progressively reduced after 5 wk to facilitate
      weaning by the end of wk 7. At the beginning of wk 9, all calves received the MIX
      diet and remained on trial for an additional 3 wk. Feeding behavior was recorded
      from video for 4d during wk 6, 8, 9, and 11. In wk 6, calves fed MIX spent more
      time feeding than calves fed COM (56.7 vs. 46.8 min/d). In wk 8, calves fed MIX
      spent more time feeding (174.0 vs. 139.1 min/d) and had a lower rate of intake
      (11.5 vs. 14.7 g/min) compared with calves fed COM. Meal frequency was similar
      between treatments (12.2 meals/d). Diurnal feeding patterns in wk 8 were also
      affected by feed presentation, with calves fed MIX spending less time feeding at
      time of feed delivery and more time feeding throughout the rest of the daylight
      hours than calves fed COM. Diurnal feeding patterns of hay and concentrate in wk
      8 differed for calves fed COM, with more time spent consuming hay at time of feed
      delivery and less time spent consuming hay throughout the rest of the day. Once
      calves previously fed COM were transitioned to the MIX diet in wk 9, meal
      frequency, meal duration, and diurnal feeding patterns were similar between
      treatments: both treatments spent similar amounts of time feeding (173.9 min/d)
      and had similar peaks in feeding activity at time of feed delivery, sunrise, and
      sunset. Provision of hay and concentrate to young calves as a mixed ration,
      compared with separate components, increases time spent feeding and results in
      more evenly distributed diurnal feeding patterns. However, differences in feeding
      patterns resulting from feed presentation did not persist after 8 wk of age, when
      all calves were fed a mixed ration.

PMID- 24035019
TI  - Short-term effects of dietary trans fatty acids compared with saturated fatty
      acids on selected measures of inflammation, fatty acid profiles, and production
      in early lactating Holstein dairy cows.
AB  - Feeding rations supplemented with fats may provide an opportunity to manipulate
      the health and performance of dairy cows; however, the relative effects of
      specific fats, such as trans fatty acids (TFA), are poorly understood. The
      objective of this study was to investigate the effects of a ration supplemented
      with TFA on the fatty acid (FA) profile of peripheral blood mononuclear cells
      (PBMC), plasma lipids, and milk; the gene expression of inflammatory markers;
      production of acute phase proteins; and production performance in early lactating
      dairy cows. Trans fat was fed at 0, 1.5, and 3% of dry matter, replacing (1:1
      wt:wt) saturated fatty acids (SFA). Multiparous lactating Holstein cows at 7 d in
      milk (n=12) were randomly assigned to a treatment sequence in a 3 * 3 balanced
      Latin square design; each period lasted 14 d. Milk and heparinized blood were
      collected on d 0 (pretreatment) and on d 10 and 14 of each period. Plasma was
      collected and solid-phase extraction was used to isolate plasma phospholipids and
      nonesterified fatty acids. Additionally, PBMC were isolated for FA analysis and
      gene expression analysis by reverse transcription-PCR using bovine RPS9 as the
      endogenous control. The FA composition of PBMC, plasma lipid fractions, and milk
      were analyzed by gas chromatography. Data were analyzed using the MIXED procedure
      (SAS Institute Inc., Cary, NC). As dietary TFA increased, the percentage of some
      18:1 trans isomers increased in PBMC, plasma lipids, and milk. Dietary TFA had no
      detectable effect on mRNA expression of proinflammatory TNFalpha or IL6.
      Expression of IL1beta and ICAM1 decreased with increasing TFA. In addition,
      supplementation of TFA did not affect percentages of milk fat, protein, lactose,
      or solids-not-fat, or somatic cell count. Overall, dietary TFA increased the
      trans FA present in PBMC, plasma lipids, and milk; however, dietary TFA decreased
      PBMC expression of some of the proinflammatory markers tested at the mRNA level
      compared with SFA in early lactating dairy cows. Together, these findings provide
      evidence that over short period of times, dietary TFA might be slightly less
      immune-stimulatory than dietary SFA.

PMID- 24035020
TI  - Nutritive value, fermentation characteristics, and in situ disappearance kinetics
      of sorghum silage treated with inoculants.
AB  - Fibrolytic enzymes and microbial inoculants have the potential to improve the
      value of sorghum feedstuff and feedstock. An experiment was conducted to
      determine nutritive value, ensiling characteristics, and in situ disappearance
      kinetics of 4 sorghum (Sorghum bicolor L.) silage varieties: Dairy Master BMR
      (DBMR; brown midrib; Richardson Seed, Vega, TX), PS 747 (PS; photoperiod
      sensitive; Pogue Seed, Kenedy, TX), Silo 700D (S700D; conventional forage type;
      Richardson Seed), and MMR 381/73 (MMR; conventional forage type; Richardson Seed)
      pretreated with fibrolytic enzyme (xylanase plus cellulase, XC; 50:50 mixture of
      Cellulase Plus and Xylanase Plus; Dyadic, Juniper, FL) or microbial [Promote ASB
      (Lactobacillus buchneri and Lactobacillus plantarum); Cargill Animal Nutrition,
      Indianapolis, IN; PRO] inoculants. The greatest yield was for cultivar PS and the
      least for MMR. Neutral detergent fiber (NDF) concentration was least for XC
      treated silage, and acid detergent fiber (ADF) concentration was least for XC-
      and PRO-treated silage. When silage was treated with XC, concentrations of NDF
      concentrations decreased, on average, 4.81% across all cultivars and ADF
      concentrations decreased, on average, 3.23% in all cultivars except MMR.
      Inoculant PRO reduced the NDF concentration of DBMR by 6.47%. The ADF
      concentrations of DBMR and PS treated with PRO were decreased by 3.25%. Treating
      sorghum silage with XC or PRO reduced the NDF and ADF fractions, which increased
      cell wall degradability. In vitro true digestibility was greatest for PRO-treated
      DBMR, whereas acid detergent lignin was least for PRO-treated DBMR. Aerobic
      stability was not improved by PRO; however, aerobic stability of XC-treated MMR
      was 63 h greater than that of the control. Acetate concentrations were greatest
      for XC-treated MMR, which explains the 63-h improvement in aerobic stability due
      to the inhibition of fungi. However, inoculant PRO did not improve yeast and mold
      counts or aerobic stability of sorghum silage compared with the control, which
      may be due to the lesser acetate concentrations, especially of PRO-treated S700D
      silage. Generally, in situ disappearance kinetics were improved with the
      application of XC and PRO, and XC had the greatest effect on silage with greater
      NDF and ADF concentrations.

PMID- 24035021
TI  - Milk volatile organic compounds and fatty acid profile in cows fed timothy as
      hay, pasture, or silage.
AB  - Nutrient composition and organoleptic properties of milk can be influenced by cow
      diets. The objective of this study was to evaluate the forage type effects on
      volatile organic compounds, fatty acid (FA) profile, and organoleptic properties
      of milk. Timothy grass was fed as hay, pasture, or silage during a period of 27 d
      to a group of 21 cows in a complete block design based on days in milk. Each cow
      also received 7.2 kg/d of a concentrate mix to meet their nutrient requirements.
      Forage dry matter intake averaged 13.9 kg/d and was not different among
      treatments. Milk yield was higher for cows fed pasture, intermediate for cows fed
      silage, and lowest for cows fed hay. However, milk fat content was higher for
      cows fed hay and silage, compared with cows fed pasture. As a result, fat
      corrected milk and fat yield were not different among treatments. Increasing the
      supply of dietary cis-9,cis-12 18:2 (linoleic acid) and cis-9,cis-12,cis-15 18:3
      (alpha-linolenic acid) when feeding pasture enhanced the concentration of these 2
      essential FA in milk fat compared with feeding hay or silage. Moreover, the ratio
      of 16:0 (palmitic acid) to cis-9 18:1 (oleic acid), which is closely related to
      the melting properties of milk fat, was lower in milk from cows on pasture than
      in milk from cows fed hay or silage. Cows fed hay produced milk with higher
      levels of several free FA and gamma-lactones, but less pentanal and 1-pentanol.
      More dimethyl sulfone and toluene were found in milk of cows on pasture. Cows fed
      silage produced milk with higher levels of acetone, 2-butanone, and alpha-pinene.
      Results from a sensory evaluation showed that panelists could not detect a
      difference in flavor between milk from cows fed hay compared with silage.
      However, a significant number of assessors perceived a difference between milk
      from cows fed hay compared with milk from cows fed pasture. In a sensory ranking
      test, the percentage of assessors ranking for the intensity of total (raw milk,
      fresh milk, and farm milk), sweet (empyreumatic, vanilla, caramel, and sugar),
      and grassy (grass, leafy vegetable, and plant) flavors was higher for milk from
      cows fed pasture compared with hay and silage. Using timothy hay, pasture, or
      silage harvested at a similar stage of development, the current study shows that
      the taste of milk is affected by the forage type fed to cows. More research is,
      however, needed to establish a link between the sensory attributes of milk and
      the observed changes in volatile organic compounds and FA profile.

PMID- 24035022
TI  - Genetic analyses of claw health in Norwegian Red cows.
AB  - The aim of this study was genetic analyses of claw health in Norwegian Red. Claw
      health status at claw trimming has, since 2004, been recorded in the Norwegian
      Dairy Herd Recording System. The claw trimmer records whether the cow has normal
      (healthy) claws or if one or more claw disorders are present. Nine defined claw
      disorders were recorded: corkscrew claw (CSC), heel horn erosion (HH), dermatitis
      (DE), sole ulcer (SU), white line disorder (WLD), hemorrhage of sole and white
      line (HSW), interdigital phlegmon (IDP), lameness (LAME), and acute trauma (AT).
      Data from 2004 to 2011, with a total of 204,892 claw health records, were
      analyzed. The disorders were defined as binary traits with 1 record per cow per
      lactation. Further, 3 groups of claw disorders were analyzed: infectious claw
      disorders (INFEC, containing HH, DE, and IDP); laminitis-related claw disorders
      (LAMIN, containing SU, WLD, and HSW); and overall claw disorder. The 9 single
      traits and the 3 groups were analyzed using univariate threshold sire models.
      Multivariate threshold models were performed for the 5 most frequent single
      traits (CSC, HH, DE, SU, and WLD) and for CSC together with the grouped traits
      INFEC and LAMIN. Posterior mean of heritability of liability ranged from 0.04 to
      0.23, where CSC had the highest heritability. The posterior standard deviations
      of heritability were low, between 0.01 and 0.03, except for IDP (0.06).
      Heritability of liability to INFEC and LAMIN were both 0.11 and for overall claw
      disorders, the heritability was 0.13. Posterior means of the genetic correlation
      among the 5 claw disorders varied between 0.02 and 0.79, and the genetic
      correlations between DE and HH (0.65) and between WLD and SU (0.79) were highest.
      Genetic correlation between INFEC and CSC was close to zero (0.06), between LAMIN
      and CSC it was 0.31, and between LAMIN and INFEC it was 0.24. The results show
      that claw disorders are sufficiently heritable for genetic evaluation and
      inclusion in the breeding scheme. At present, data are scarce with few recorded
      daughters per sire. Claw trimming records from more herds would therefore be
      beneficial for routine genetic evaluation of claw health. 

PMID- 24035023
TI  - Identification of the critical amino acid residues of immunoglobulin E and
      immunoglobulin G epitopes on alphas1-casein by alanine scanning analysis.
AB  - alphas1-Casein represents one of the major allergens causing cow milk allergy.
      Few studies have clearly evaluated immunological relationships between IgE- and
      IgG-binding epitopes of alphas1-casein. This study aimed to map IgE- and IgG
      binding epitopes of alphas1-casein by the serology method, and identify the
      critical amino acids of alphas1-casein by alanine scanning analysis. Our initial
      data revealed IgE-binding epitopes located in the sequences of AA 126 to 140, AA
      6 to 20, AA 171 to 185, and AA 11 to 25. The sequences at AA 21 to 35, AA 56 to
      70, and AA 161 to 175 were recognized by IgG antibodies. The alanine scanning
      analysis showed that IgE- and IgG-binding epitopes share the same critical AA:
      arginine at position 22 and phenylalanine at position 23. Results obtained from
      this study will provide necessary information to alter the cDNA to encode a
      protein with reduced IgE- or IgG-binding capacity. 

PMID- 24035024
TI  - Evaluation of rumen-protected lysine supplementation to lactating dairy cows
      consuming increasing amounts of distillers dried grains with solubles.
AB  - Twenty multiparous Holstein cows were used in four 5 * 5 Latin squares to
      determine the effects of feeding increasing amounts of distillers dried grains
      with solubles (DDGS) in diets with or without the supplementation (60 g/d) of a
      rumen-protected Lys (RPL) product (AminoShure-L, 38% l-Lys; Balchem Encapsulates,
      New Hampton, NY) on milk yield and composition and plasma concentration of AA.
      Dietary treatments were (1) control (CON; no DDGS), (2) 10% DDGS (10DG), (3) 20%
      DDGS (20DG), (4) 10% DDGS plus RPL (10DGRPL), and (5) 20% DDGS plus RPL
      (20DGRPL). Diets were formulated using the Cornell-Penn-Miner Dairy model (CPM
      v3.0; http://cahpwww.vet.upenn.edu/node/77) to provide a predicted decreasing
      supply of Lys (117, 99, and 91% of requirements) for the CON, 10DG, and 20DG
      diets, respectively. Addition of RPL to the 10DG and 20DG diets (unsupplemented
      diets) resulted in 2 additional treatments, 10DGRPL and 20DGRPL diets,
      respectively. The 10DGRPL and 20DGRPL diets met 110 and 100% of the Lys
      requirements, respectively. Periods lasted 21d, with the last 3d for data
      collection. Compared with cows fed the CON diet, cows fed diets with DDGS had a
      similar dry matter intake (DMI; 25.4 +/- 0.88 kg/d), milk yield (30.7 +/- 1.67
      kg/d), and composition, except for protein percentage, which was higher (3.15 vs.
      3.21 +/- 0.05%) and resulted in higher (0.94 vs. 1.00 +/- 0.05 kg/d) protein
      yield by cows fed diets containing 20% DDGS. Unexpectedly, despite diets being
      formulated based on predicted DMI of 23.3 kg/d and milk yield of 38.5 kg/d, cows
      had a greater DMI and lower milk yield across all treatments, which resulted in
      diets that were predicted by CPM Dairy to supply sufficient amounts of Lys (140,
      118, and 104% of requirement for the CON, 10 DG, and 20 DG diet, respectively)
      and consequently, supplementation with RPL did not have an effect on milk
      production or composition. Plasma concentration of Lys decreased (11.8%) as DDGS
      inclusion increased. For other essential AA, plasma concentrations of cows fed
      diets with DDGS were lower for Arg, His, and Val and greater for Leu and Met
      compared with cows fed the CON diet. Supplementation with RPL failed to decrease
      the plasma concentration of other essential AA, which provides support that Lys
      was not limiting.

PMID- 24035025
TI  - Unraveling the genetic architecture of environmental variance of somatic cell
      score using high-density single nucleotide polymorphism and cow data from
      experimental farms.
AB  - In recent years, it has been shown that not only is the phenotype under genetic
      control, but also the environmental variance. Very little, however, is known
      about the genetic architecture of environmental variance. The main objective of
      this study was to unravel the genetic architecture of the mean and environmental
      variance of somatic cell score (SCS) by identifying genome-wide associations for
      mean and environmental variance of SCS in dairy cows and by quantifying the
      accuracy of genome-wide breeding values. Somatic cell score was used because
      previous research has shown that the environmental variance of SCS is partly
      under genetic control and reduction of the variance of SCS by selection is
      desirable. In this study, we used 37,590 single nucleotide polymorphism (SNP)
      genotypes and 46,353 test-day records of 1,642 cows at experimental research
      farms in 4 countries in Europe. We used a genomic relationship matrix in a double
      hierarchical generalized linear model to estimate genome-wide breeding values and
      genetic parameters. The estimated mean and environmental variance per cow was
      used in a Bayesian multi-locus model to identify SNP associated with either the
      mean or the environmental variance of SCS. Based on the obtained accuracy of
      genome-wide breeding values, 985 and 541 independent chromosome segments
      affecting the mean and environmental variance of SCS, respectively, were
      identified. Using a genomic relationship matrix increased the accuracy of
      breeding values relative to using a pedigree relationship matrix. In total, 43
      SNP were significantly associated with either the mean (22) or the environmental
      variance of SCS (21). The SNP with the highest Bayes factor was on chromosome 9
      (Hapmap31053-BTA-111664) explaining approximately 3% of the genetic variance of
      the environmental variance of SCS. Other significant SNP explained less than 1%
      of the genetic variance. It can be concluded that fewer genomic regions affect
      the environmental variance of SCS than the mean of SCS, but genes with large
      effects seem to be absent for both traits. 

PMID- 24035026
TI  - Short communication: In vitro antimicrobial susceptibility of Mycoplasma
      agalactiae strains isolated from dairy goats.
AB  - This study examined the susceptibility to several antimicrobials of 28 isolates
      of Mycoplasma agalactiae obtained from goats in a region (southeastern Spain)
      where contagious agalactia is endemic. For each isolate, the minimum inhibitory
      concentration (MIC) against 12 antimicrobials of the quinolone, macrolide,
      aminoglycoside, and tetracycline families was determined. The antimicrobials with
      the lowest MIC were enrofloxacin, ciprofloxacin, tylosin, and doxycycline, all
      with MIC90 (concentration at which growth of 90% of the isolates is inhibited) <1
      ug/mL. Norfloxacin (a quinolone) showed a wide MIC range (0.1-12.8 ug/mL),
      suggesting a resistance mechanism toward this antimicrobial that was not elicited
      by enrofloxacin or ciprofloxacin (the other quinolones tested). Erythromycin
      showed the highest MIC90 such that its use against Mycoplasma agalactiae is not
      recommended. Finally, Mycoplasma agalactiae isolates obtained from goat herds
      with clinical symptoms of contagious agalactia featured higher MIC90 and MIC50
      (concentration at which growth of 50% of the isolates is inhibited) values for
      many of the antimicrobials compared with isolates from asymptomatic animals. The
      relationship between the extensive use of antimicrobials in herds with clinical
      contagious agalactia and variations in MIC requires further study.

PMID- 24035027
TI  - Variation in nutrients formulated and nutrients supplied on 5 California dairies.
AB  - Computer models used in ration formulation assume that nutrients supplied by a
      ration formulation are the same as the nutrients presented in front of the cow in
      the final ration. Deviations in nutrients due to feed management effects such as
      dry matter changes (i.e., rain), loading, mixing, and delivery errors are assumed
      to not affect delivery of nutrients to the cow and her resulting milk production.
      To estimate how feed management affects nutrients supplied to the cow and milk
      production, and determine if nutrients can serve as indexes of feed management
      practices, weekly total mixed ration samples were collected and analyzed for 4
      pens (close-up cows, fresh cows, high-milk-producing, and low-milk-producing
      cows, if available) for 7 to 12 wk on 5 commercial California dairies.
      Differences among nutrient analyses from these samples and nutrients from the
      formulated rations were analyzed by PROC MIXED of SAS (SAS Institute Inc., Cary,
      NC). Milk fat and milk protein percentages did not vary as much [coefficient of
      variation (CV) = 18 to 33%] as milk yield (kg; CV = 16 to 47 %) across all
      dairies and pens. Variability in nutrients delivered were highest for
      macronutrient fat (CV = 22%), lignin (CV = 15%), and ash (CV = 11%) percentages
      and micronutrients Fe (mg/kg; CV = 48%), Na (%; CV = 42%), and Zn (mg/kg; CV =
      38%) for the milking pens across all dairies. Partitioning of the variability in
      random effects of nutrients delivered and intraclass correlation coefficients
      showed that variability in lignin percentage of TMR had the highest correlation
      with variability in milk yield and milk fat percentage, followed by fat and crude
      protein percentages. But, variability in ash, fat, and lignin percentages of
      total mixed ration had the highest correlation with variability in milk protein
      percentage. Therefore, lignin, fat, and ash may be the best indices of feed
      management to include effects of variability in nutrients on variability in milk
      yield, milk fat, and milk protein percentages in ration formulation models.

PMID- 24035028
TI  - Crystallization mechanisms in cream during ripening and initial butter churning.
AB  - The temperature treatment of cream is the time-consuming step in butter
      production. A better understanding of the mechanisms leading to partial
      coalescence, such as fat crystallization during ripening and churning of the
      cream, will contribute to optimization of the production process. In this study,
      ripening and churning of cream were performed in a rheometer cell and the
      mechanisms of cream crystallization during churning of the cream, including the
      effect of ripening time, were investigated to understand how churning time and
      partial coalescence are affected. Crystallization mechanisms were studied as
      function of time by differential scanning calorimetry, nuclear magnetic resonance
      and by X-ray scattering. Microstructure formation was investigated by small
      deformation rheology and static light scattering. The study demonstrated that
      viscosity measurements can be used to detect phase inversion of the emulsion
      during churning of the cream in a rheometer cell. Longer ripening time (e.g., 5h
      vs. 0 h) resulted in larger butter grains (91 vs. 52 um), higher viscosity (5.3
      vs. 1.3 Pa . s), and solid fat content (41 vs. 13%). Both ripening and churning
      time had an effect on the thermal behavior of the cream. Despite the increase in
      solid fat content, no further changes in crystal polymorphism and in melting
      behavior were observed after 1h of ripening and after churning. The churning time
      significantly decreased after 0.5h of ripening, from 22.9 min for the cream where
      no ripening was applied to 16.23 min. Therefore, the crystallization state that
      promotes partial coalescence (i.e., aggregation of butter grains) is obtained
      within the first hour of cream ripening at 10  degrees C. The present study adds
      knowledge on the fundamental processes of crystallization and polymorphism of
      milk fat occurring during ripening and churning of cream. In addition, the dairy
      industry will benefit from these insights on the optimization of butter
      manufacturing.

PMID- 24035030
TI  - Increasing frequency of feline cytauxzoonosis cases diagnosed in western Kentucky
      from 2001 to 2011.
AB  - Feline cytauxzoonosis is a rapidly progressing and usually fatal disease in
      domestic cats caused by the tick-borne pathogen, Cytauxzoon felis. The primary
      reservoir host for this protozoan parasite is the bobcat (Lynx rufus). In this
      retrospective study, we have examined the positive cases of feline cytauxzoonosis
      identified at Murray State University's Breathitt Veterinary Center, a regional
      diagnostic facility located in Hopkinsville, Kentucky, between January 2001 and
      December 2011. Center records reveal that there has been an increase in the rate
      of diagnosis of domestic feline infection with C. felis over that 10-year span
      with the majority of cases (75%) occurring between 2006 and 2011. The infection
      was diagnosed from March through October and showed a single peak in May,
      corresponding well with the questing period for the lone star tick, Amblyomma
      americanum, a known vector of C. felis. 

PMID- 24035029
TI  - Impact of physical activity after cancer diagnosis on survival in patients with
      recurrent colon cancer: Findings from CALGB 89803/Alliance.
AB  - BACKGROUND: The impact of physical activity on survival outcomes in patients with
      recurrent colon cancer has not been studied. We tested the association between
      the level of postdiagnosis physical activity and survival outcomes of patients
      with recurrent colon cancer. PATIENTS AND METHODS: We conducted a prospective
      observational study of 237 patients with stage III colon cancer who had
      recurrence of disease. Physical activity was measured approximately 6 months
      after the completion of therapy (14 months after surgical resection) but before
      detection of recurrent disease. The primary end point of the study was survival
      time after recurrence. RESULTS: The hazard ratio comparing patients who reported
      at least 18 metabolic equivalent task (MET) hours per week of physical activity
      with those engaging in < 3 MET hours per week was 0.71 (95% confidence interval,
      0.46-1.11). Increasing total MET hours of physical activity per week was
      associated with a borderline statistical significance trend for improved survival
      after recurrence (P = .052). The benefit of physical activity on survival was not
      significantly modified by sex, body mass index (BMI), number of positive lymph
      nodes, age, baseline performance status, adjuvant chemotherapy regimen, or
      recurrence-free survival period. CONCLUSION: To our knowledge, this is the first
      study investigating the association of physical activity with survival outcome of
      patients with recurrent colon cancer. Although the association exceeded our
      predefined P trend < .05 for statistical significance, these findings warrant
      further studies of physical activity in patients with recurrent colorectal
      cancer.

PMID- 24035031
TI  - Failed pyeloplasty in children: revisiting the unknown.
AB  - OBJECTIVE: To perform a critical analysis of the management of the pediatric
      failed pyeloplasty in a large tertiary center. The ideal approach to this rare
      entity is not well established. METHODS: Retrospective record review of children
      undergoing pyeloplasty from 2000 to 2010. All cases that required any type of
      reintervention, excluding stent removal, were analyzed. Data collected included:
      demographics, indication for and modality of the initial surgery, presence of
      crossing vessels, mode of diagnosis of failure, and type(s) of reintervention
      with the correspondent success rate(s). RESULTS: Overall, pyeloplasty failure
      rate was 27 per 455 patients (5.9%). Age, initial indication for pyeloplasty, and
      modality of surgery (open vs laparoscopic) yielded similar failure rates.
      Indications for reintervention were as follows: worsening asymptomatic
      hydronephrosis 16 of 27 (59%), pain 7 of 27 (26%), urosepsis 2 of 27 (7.5%), and
      others 2 of 27 (7.5%). Eight of 27 (30%) improved with 1, 14 of 27 (52%) had 2,
      and 5 of 27 (18%) required 3 reinterventions, respectively. Mean interval between
      the first operation and subsequent interventions was 19.3, 24.9, and 27 months
      for the first, second, and third reinterventions, respectively. Modalities of
      reintervention with respective success rates were as follows: double J stent
      insertion 16% (6%), endopyelotomy 18% (50%), redo pyeloplasty 12% (92%), and
      ureterocalicostomy 4% (100%). Only 1 patient (7%) was documented to have a missed
      crossing vessel. All patients were stable and doing well after a mean follow-up
      of 56 months after the first operation. CONCLUSION: According to this series,
      more invasive and definitive techniques, such as redo pyeloplasty and
      ureterocalicostomy, are more successful than minimally invasive ones to treat
      failed pyeloplasty and should probably be offered sooner rather than later.

PMID- 24035032
TI  - Comparison of different ureteroscope sizes in treating ureteral calculi in adult
      patients.
AB  - OBJECTIVE: To compare the success and complication rates of a 4.5-6.5F semirigid
      ureteroscope (S-URS) with an 8.5-11.5F S-URS in treating ureteral stones in adult
      patients. MATERIALS AND METHODS: Fifty-two patients with ureteral stones, who
      were treated with 4.5-6.5F S-URS (group 1) and 52 patients who were treated with
      8.5-11.5F S-URS (group 2) were compared retrospectively using a matched-pair
      analysis. The size, lateralization, location, and impaction of the stones and
      also the patient age, gender, body mass index, and the presence of hydronephrosis
      were used as the matching parameters. The stones were fragmented with Holmium-YAG
      laser. RESULTS: The matching parameters were comparable between the 2 groups. The
      stone-free rates were 88.5% in group 1 and 84.6% in group 2 (P = .566) after a
      single procedure. The mean operative times for groups 1 and 2 were 32.7 +/- 5.8
      and 30.2 +/- 5.4 minutes, respectively (P = .06). Postoperative hematuria was
      detected in 1.9% and 13.5% of patients in groups 1 and 2 (P = .027). Ureteral
      balloon dilation was needed in 1.9% and 15.4% of patients in groups 1 and 2,
      respectively (P = .015). Mucosal injury was observed in 1.9% and 13.5% of the
      patients in groups 1 and 2, respectively (P = .027). No major complications were
      noted in either group. CONCLUSION: Although the stone-free rates and operative
      times were similar between the 2 groups, a 4.5-6.5F ureteroscope can reduce the
      need for ureteral balloon dilation and some minor complications, such as mucosal
      injury and postoperative hematuria, in adult patients.

PMID- 24035033
TI  - Editorial comment.

PMID- 24035035
TI  - Laparoscopic ureteral reimplantation with extracorporeal tailoring and direct
      nipple ureteroneocystostomy for adult obstructed megaureter: a novel technique.
AB  - INTRODUCTION: To describe a novel technique using extracorporeal tailoring and an
      inverted ureteral nipple to perform laparoscopic transperitoneal ureteral
      reimplantation for adult obstructed megaureter and our initial experience with 10
      patients. TECHNICAL CONSIDERATIONS: Ten patients (mean age 39.2 years [range, 21
      62]) with adult obstructed megaureter underwent transperitoneal laparoscopic
      ureteral reimplantation by a 3- or 4-port technique. In each case, the affected
      ureter was freed and delivered out of the peritoneal cavity through the
      ipsilateral 12-mm port. The lower end of the ureter was tailored by approximately
      6 cm, and the tip was folded back onto itself and secured with absorbable sutures
      to form a nipple. A double-J stent was placed, the entire assembly was carefully
      replaced into the abdomen, and the ureter was reimplanted into the posterolateral
      wall of the bladder. CONCLUSION: Surgery was successful in all the 10 patients
      without the need for open conversion. At a mean follow-up of 17 months, all
      patients were asymptomatic, and hydronephrosis was relieved in 9 cases.
      Laparoscopic ureteral reimplantation with extracorporeal tailoring and direct
      nipple ureteroneocystostomy is an easy, safe, and effective procedure for adult
      obstructed megaureter.

PMID- 24035036
TI  - Editorial comment.

PMID- 24035037
TI  - Inhibitory role of the spinal galanin system in the control of micturition.
AB  - OBJECTIVE: To investigate the effect of intrathecal galanin on the micturition
      reflex in rats. METHODS: Continuous cystometrograms (0.04 mL/min infusion rate)
      were performed in female Sprague-Dawley rats (225-248 g) under urethane
      anesthesia. After stable micturition cycles were established, galanin was
      administered intrathecally to evaluate changes in bladder activity. Then, to
      examine the involvement of opioid systems in the galanin effects, galanin was
      administered intrathecally when the first bladder contraction was observed after
      intrathecal administration of naloxone, an opioid receptor antagonist. RESULTS:
      Intrathecal administration of galanin (1-10 MUg) increased intercontraction
      intervals in a dose-dependent fashion. Intrathecal administration of galanin (1
      10 MUg) also increased pressure threshold in a dose-dependent fashion. These
      inhibitory effects of galanin (10 MUg) were partially antagonized by intrathecal
      administration of naloxone (10 MUg). CONCLUSION: These results indicate that in
      urethane-anesthetized rats, galanin delays the onset of micturition through
      activation of the opioid mechanism, suggesting the inhibitory role of galanin
      system in the control of the micturition reflex.

PMID- 24035039
TI  - An intention to achieve better postnatal in-hospital-growth for preterm infants:
      adjustable protein fortification of human milk.
AB  - OBJECTIVE: We assessed the effect of human milk (HM) fortification with extra
      protein supplement by an adjustable protein fortification method according to the
      weekly blood urea nitrogen (BUN) levels on growth in hospitalized preterm
      infants. METHOD: A prospective observational intervention study in 58 preterms
      born <=32 weeks of gestation and fed with breast milk was conducted. Preterms who
      were given a commercial HM fortifier which provides an additional protein of 0.8
      g/3 scales according to the standard feeding strategy served as a historical
      control group. Infants who were given extra protein in addition to the HM
      fortifier with another commercial protein supplement which provides an additional
      protein of 2.2g/1 scale comprised the intervention group. Additional protein
      supplementation was adjusted according to BUN levels weekly in the intervention
      group. Weight gain velocities (g/kg/day), length, head circumferences (HC) gain
      velocities (mm/day) and daily growth indexes for weight, height and HC
      (percentage per day) were calculated. RESULTS: The median amount of daily enteral
      protein intake [4 (3.4-4.6) vs. 2.78 (2.1-3.1) g/kg/day, p < 0.0001] was
      significantly higher in the interventional group. Length (p = 0.008) and HC (p <
      0.0001) gain velocities were significantly higher in the intervention group.
      Daily growth indexes for weight (2.2% vs. 1.8%, p = 0.026), for length (0.4% vs.
      0.3%, p = 0.027) and for HC (0.48% vs. 0.36% per day, p = 0.003) were
      significantly higher in the intervention group. CONCLUSION: A higher protein
      intake by adjustable protein fortification method without energy or volume change
      leads to improved postnatal in-hospital-growth in very low birth weight infants.

PMID- 24035040
TI  - SGK1 is regulated by metabolic-related factors in 3T3-L1 adipocytes and
      overexpressed in the adipose tissue of subjects with obesity and diabetes.
AB  - AIMS: The present study aimed to investigate the pathophysiological role of SGK1
      in the development of metabolic syndrome by investigating the expression and
      regulation of serum and glucocorticoid-inducible kinase 1 (SGK1) in adipose
      tissues in obesity and diabetes. METHODS: SGK1 expression in adipose tissue was
      investigated using reverse transcription polymerase chain reaction (RT-PCR) and
      immunohistochemistry. SGK1 regulation in differentiated 3T3-L1 adipocytes by
      metabolic-related factors was assessed using Northern blot analysis. Humans with
      obesity and type 2 diabetes and KKAy and db/db mice were used to evaluate SGK1
      expression in the adipose tissue of subjects with obesity and diabetes using
      quantitative real-time PCR and Western blot analysis. RESULTS: SGK1 was expressed
      in white adipose tissue as shown by mRNA and protein levels. Aldosterone and
      glucocorticoids stimulated SGK1 expression in a time- and dose-dependent manner,
      whereas PPAR-gamma agonists inhibited SGK1 expression in differentiated 3T3-L1
      adipocytes. Furthermore, SGK1 mRNA and protein were overexpressed in the adipose
      tissue of mice and humans with obesity and type 2 diabetes. CONCLUSION:
      Aldosterone, glucocorticoids and other factors contribute to excessive SGK1
      expression in adipose tissue. This excessive SGK1 expression may be related to
      adipose tissue dysfunction, which may contribute to the development of obesity,
      diabetes and metabolic syndrome.

PMID- 24035041
TI  - Why aren't we doing more to safeguard vulnerable adults from thermal injuries?

PMID- 24035042
TI  - Clinical implications of serial serum N-terminal prohormone brain natriuretic
      peptide levels in the prediction of outcome in children with dilated
      cardiomyopathy.
AB  - N-terminal prohormone brain natriuretic peptide (NT-proBNP) is known to be
      valuable as a prognostic marker for the management of heart failure. This study
      aimed to assess the serial changes of serum NT-proBNP levels as a prognostic
      factor for outcomes of pediatric dilated cardiomyopathy (DC). A retrospective
      study reviewed echocardiographic measurements and serum NT-proBNP levels obtained
      at the time of diagnosis, 3 and 6 months after diagnosis, and at the last follow
      up in 68 children with DC. They were classified into 3 groups according to the
      last follow-up of the left ventricular (LV) function: group I (n = 37) with LV
      fractional shortening (FS) >=25%, group II (n = 15) with 10% <= LVFS < 25%, and
      group III (n = 16) with LVFS <10% or cardiac death. The median age at diagnosis
      was 30 months and median duration of follow-up was 45 months (range 8 to 108
      months). The origin of DC varied. Serial serum NT-proBNP levels showed
      statistically significant differences among the 3 groups. Although initial levels
      of serum NT-proBNP at diagnosis were not different from each other, group III
      maintained a higher NT-proBNP level throughout the duration of the follow-up. On
      multivariate Cox analysis, only the NT-proBNP level at 3 months was a significant
      predictor of an adverse outcome (hazard ratio 2.012, p = 0.028). The percent
      changes of NT-proBNP from diagnosis were not significant. Patients with DC with a
      serum NT-proBNP level >=681 pg/ml at 3 months after diagnosis showed an increased
      risk of severe LV dysfunction or cardiac death (p <0.001, area under the curve =
      0.846). In conclusion, the level of NT-proBNP in serum at 3 months after
      diagnosis could predict an adverse outcome in pediatric DC and could be used as a
      guide for long-term treatment plans.

PMID- 24035043
TI  - Revealing in vivo glucose utilization of Gluconobacter oxydans 621H Deltamgdh
      strain by mutagenesis.
AB  - Gluconobacter oxydans, belonging to acetic acid bacteria, is widely used in
      industrial biotechnology. In our previous study, one of the main glucose
      metabolic pathways in G. oxydans 621H was blocked by the disruption of the mgdh
      gene, which is responsible for glucose oxidation to gluconate on cell membrane.
      The resulting 621H Deltamgdh mutant strain showed an enhanced growth and biomass
      yield on glucose. In order to further understand the intracellular utilization of
      glucose by 621H Deltamgdh, the functions of four fundamental genes, namely
      glucokinase-encoding glk1 gene, soluble glucose dehydrogenase-encoding sgdh gene,
      galactose-proton symporter-encoding galp1 and galp2 genes, were investigated. The
      obtained metabolic characteristics of 621H Deltamgdh Deltaglk1 and 621H Deltamgdh
      Deltasgdh double-gene knockout mutants showed that, in vivo, glucose is
      preferentially phosphorylated to glucose-6-phosphate by glucokinase rather than
      being oxidized to gluconate by soluble glucose dehydrogenase. In addition,
      although the galactose-proton symporter-encoding genes were proved to be glucose
      transporter genes in other organisms, both galp genes (galp 1 and galp2) in G.
      oxydans were not found to be involved in glucose uptake system, implying that
      other unknown transporters might be responsible for transporting glucose into the
      cells. 

PMID- 24035044
TI  - The role of soluble thrombomodulin in the risk stratification and prognosis
      evaluation of septic patients in the emergency department.
AB  - INTRODUCTION: Soluble thrombomodulin (sTM) is a sensitive marker of endothelial
      damage. In this study we investigated the role of sTM in the evaluation of the
      severity and prognosis of septic patients in the emergency department (ED).
      MATERIALS AND METHODS: A prospective, observational cohort study was performed in
      the ED of an urban, university hospital. Patients who had suspected infection
      with two or more criteria of systemic inflammatory response syndrome were
      consecutively enrolled. sTM, D-Dimer and procalcitonin levels were measured on
      enrollment, and the Mortality in Emergency Department Sepsis (MEDS) score was
      calculated. A 30-day follow-up was performed for all patients. RESULTS: A total
      of 372 patients with sepsis, 210 patients with severe sepsis and 98 patients with
      septic shock were enrolled in this study. According to the disease severity,
      patients were divided into sepsis subgroup and severe sepsis subgroup (including
      septic shock). In addition, patients were divided into survivors subgroup and non
      survivors subgroup according to the 30-day mortality. Plasma sTM levels in
      patients with severe sepsis were higher than those with sepsis (P<0.001).
      Compared with survivors, non-survivors has higher plasma sTM levels (P<0.001).
      Multivariate logistic regression analysis showed that sTM was an independent
      predictor of severe sepsis (odds ratio 1.11) and 30-day mortality (odds ratio
      1.059). Receiver operating characteristic curve analysis showed that sTM was a
      useful parameter in prediction of severe sepsis (0.859) and 30-day mortality
      (0.78). Compared with the MEDS score alone, combination of sTM and the MEDS score
      can improve the accuracy in prediction of severe sepsis and 30-day mortality.
      CONCLUSIONS: sTM is a valuable biomarker in the risk stratification and prognosis
      evaluation of ED sepsis. Furthermore, sTM can enhance the ability of the MEDS
      score in prediction of severe sepsis and 30-day mortality.

PMID- 24035045
TI  - Outpatient treatment of symptomatic pulmonary embolism: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Patients with acute deep vein thrombus (DVT) can safely be treated as
      outpatients. However the role of outpatient treatment in patients diagnosed with
      a pulmonary embolism (PE) is controversial. We sought to determine the safety of
      outpatient management of patients with acute symptomatic PE. MATERIALS AND
      METHODS: A systematic literature search strategy was conducted using MEDLINE,
      EMBASE, the Cochrane Register of Controlled Trials and all EBM Reviews. Pooled
      proportions for the different outcomes were calculated. RESULTS: A total of 1258
      patients were included in the systematic review. The rate of recurrent venous
      thromboembolism (VTE) in patients with PE managed as outpatients was 1.47% (95%
      CI: 0.47 to 3.0%; I(2): 65.4%) during the 3 month follow-up period. The rate of
      fatal PE was 0.47% (95% CI: 0.16 to 1.0%; I(2): 0%). The rates of major bleeding
      and fatal intracranial hemorrhage were 0.81% (95% CI: 0.37 to 1.42%; I(2): 0%)
      and 0.29% (95% CI: 0.06 to 0.68%; I(2): 0%), respectively. The overall 3 month
      mortality rate was 1.58% (95% CI: 0.71 to 2.80%; I(2): 45%). The event rates were
      similar if employing risk stratification models versus using clinical gestalt to
      select appropriate patients for outpatient management. CONCLUSIONS: Independent
      of the risk stratification methods used, the rate of adverse events associated
      with outpatient PE treatment seems low. Based on our systematic review and pooled
      meta-analysis, low-risk patients with acute PE can safely be treated as
      outpatients if home circumstances are adequate.

PMID- 24035046
TI  - Improving specialty care follow-up after an ED visit using a unique referral
      system.
AB  - OBJECTIVE: Many patients discharged from the emergency department (ED) require
      urgent follow-up with specialty providers. We hypothesized that a unique
      specialty referral mechanism that minimized barriers would increase follow-up
      compliance over reported and historical benchmarks. METHODS: Retrospective review
      of all patients requiring urgent (within 1 month) specialty referrals in 2010
      from a safety net hospital ED to dermatology, otolaryngology, neurology,
      neurosurgery, ophthalmology, urology, plastic surgery, general surgery, or
      vascular surgery clinics. After specialist input, all patients received a
      specific follow-up appointment before ED discharge via a specific scheduling
      service. Necessity for payment at the follow-up visit was waived. RESULTS: Of the
      1174 receiving referrals, 85.6% of patients scheduled an appointment and 80.1%
      kept that appointment. After logistic regression analysis, the factors that
      remained significantly associated (P < .05) with appointment-keeping compliance
      were the specialty clinic type (dermatology, 61.5%, to ophthalmology, 98.0%),
      insurance status (other payer, 87.5%; commercial, 82.8%; Medicaid, 77.9%;
      Medicare, 85.7%; charity care program, 88.1%; self-pay, 73.0%), age (<18 years,
      80.1%; 18-34 years, 75.0%; 35-49 years, 79.2%; 50-64 years, 85.9 %; >64 years,
      93.9%), and mean length of time between ED visit and clinic appointment (kept,
      10.5 days; not kept, 14.3 days). The specialty clinic (neurology, 72.8%, to
      vascular surgery, 100%; P < .001) was significantly associated with the
      likelihood of patients to complete the appointment-making process. Race/Ethnicity
      was not associated with either scheduling or keeping an appointment. CONCLUSION:
      A referral process that minimizes barriers can achieve an 80% follow-up
      compliance rate. Age, insurance, specialty type, and time to appointment are
      associated with noncompliance.

PMID- 24035047
TI  - Cardiac risk factors and risk scores vs cardiac computed tomography angiography:
      a prospective cohort study for triage of ED patients with acute chest pain.
AB  - OBJECTIVE: The objective of the study is to evaluate cardiac risk factors and
      risk scores for prediction of coronary artery disease (CAD) and adverse outcomes
      in an emergency department (ED) population judged to be at low to intermediate
      risk for acute coronary syndrome. METHODS: Informed consent was obtained from
      consecutive ED patients who presented with chest pain and were evaluated with
      coronary computed tomography angiography (cCTA). Cardiac risk factors, clinical
      presentation, electrocardiogram, and laboratory studies were recorded; the
      Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute
      Coronary Events (GRACE) scores were tabulated. Coronary computed tomography
      angiography findings were rated on a 6-level plaque burden scale and classified
      for significant CAD (stenosis >=50%). Adverse cardiovascular outcomes were
      recorded at 30 days. RESULTS: Among 250 patients evaluated by cCTA, 143 (57%) had
      no CAD, 64 (26%) demonstrated minimal plaque (<30% stenosis), 26 (10%)
      demonstrated mild plaque (<50% stenosis), 9 (4%) demonstrated moderate single
      vessel disease (50%-70% stenosis), 2 (1%) demonstrated moderate multivessel
      disease, and 6 (2%) demonstrated severe disease (>70% stenosis). Six patients
      developed adverse cardiovascular outcomes. Among traditional cardiac risk
      factors, only age (older) and sex (male) were significant independent predictors
      of CAD. Correlation with CAD was poor for the TIMI (r = 0.12) and GRACE (r = 0.09
      0.23) scores. The TIMI and GRACE scores were not useful to predict adverse
      outcomes. Coronary computed tomography angiography identified severe CAD in all
      subjects with adverse outcomes. CONCLUSION: Among ED patients who present with
      chest pain judged to be at low to intermediate risk for acute coronary syndrome,
      traditional risk factors are not useful to stratify risk for CAD and adverse
      outcomes. Coronary computed tomography angiography is an excellent predictor of
      CAD and outcome.

PMID- 24035048
TI  - The man with a persistently runny nose.
AB  - Cerebrospinal fluid (CSF) rhinorrhea is rarely seen in the emergency department
      (ED) and most often occurs after a traumatic event. Spontaneous CSF leaks are
      much less common and are often the result of benign intracranial hypertension. If
      not recognized early on, CSF infections are the most serious consequence of this
      condition and therefore its early diagnosis and treatment are essential. This
      case report describes a patient who presented to the ED with a CSF leak not
      caused by a traumatic event. The patient presented with persistent unilateral
      rhinorrhea and headache that had previously been misdiagnosed. It describes the
      importance of early diagnosis and treatment of this serious condition. This is a
      case report of an uncommon but potentially dangerous disease that carries high
      morbidity if not diagnosed and treated early. This disease must be considered in
      the differential diagnosis of any patient who presents with persistent atraumatic
      unilateral rhinorrhea. Although CSF leaks have been portrayed in the literature,
      this case report is unique because it describes a rare manifestation of this
      condition and its diagnosis by emergency physicians. This article presents the
      case, discusses the incidence, potential causes, predisposing factors, diagnostic
      modalities and the course of treatment for this particular diagnosis.

PMID- 24035049
TI  - The fast emergency vehicle pre-emption system improved the outcomes of out-of
      hospital cardiac arrest.
AB  - PURPOSES: Ambulance response time is a major factor associated with survival in
      out-of-hospital cardiac arrests (OHCAs); the fast emergency vehicle pre-emption
      system (FASTTM) aids response time by controlling traffic signals. This eight
      year observational study investigated whether FASTTM implementation reduced
      response times and improved OHCA outcomes. METHODS: Data was prospectively
      collected from 1161 OHCAs that were not witnessed by emergency medical
      technicians from April 1, 2003, to March 31, 2011. The study took place in
      Kanazawa city, where ambulances without FASTTM (non-FASTTM-equipped) were being
      progressively replaced by new FASTTM-equipped ambulances. OHCA data, including
      the response times recorded in seconds, were collected and compared between the
      FASTTM-equipped and non-FASTTM-equipped ambulances. OHCA outcomes were
      subsequently compared in the subgroup of OHCAs managed by emergency medical
      technicians without tracheal intubation or epinephrine administration. The
      primary end-point of this study was one-year (1-Y) survival. RESULTS: The median
      response time significantly differed between the FASTTM-equipped and non-FASTTM
      equipped groups at 327 and 381 s, respectively. The 1-Y survival rates were 7.0%
      in the FASTTM-equipped group and 2.8% in the non-FASTTM-equipped group. Logistic
      regression analysis revealed that the dispatch of a FASTTM-equipped ambulance was
      an independent factor for 1-Y survival (adjusted odds ratio = 3.077, 95%
      confidence interval = 1.180-9.350). CONCLUSIONS: The FASTTM implementation
      significantly reduced ambulance response times and improved OHCA outcomes in
      Kanazawa city.

PMID- 24035050
TI  - Diffuse thrombosis secondary to Behcet's disease: a case report.
AB  - Behcet's disease is a multisystemic, potentially life-threatening condition with
      vascular involvement and thrombotic tendency. The disease course is characterized
      by exacerbations and remissions. Lower extremity vein thrombosis is the most
      frequent manifestation of vascular involvement, followed by vena cava thrombosis,
      pulmonary artery aneurysms, peripheral artery aneurysms, dural sinus thrombosis
      and abdominal aorta aneurysms. The case in this report was considered worth
      reporting due to vena cava thrombosis extending from brachiocephalic to jugular
      vein, accompanying thrombosis of the contralateral brachiocephalic vein and
      jugular veins as well as simultaneous dural sinus thrombosis, and also benefit
      from thrombolytic therapy.

PMID- 24035051
TI  - Frequent ED users: are most visits for mental health, alcohol, and drug-related
      complaints?
AB  - STUDY OBJECTIVE: To determine whether frequent emergency department (ED) users
      are more likely to make at least one and a majority of visits for mental health,
      alcohol, or drug-related complaints compared to non-frequent users. METHODS: We
      performed a retrospective cohort study exploring frequent ED use and ED diagnosis
      at a single, academic hospital and included all ED patients between January 1 and
      December 31, 2010. We compared differences in ED visits with a primary
      International Classification of Diseases, 9th Revision visit diagnosis of mental
      health, alcohol or drug-related diagnoses between non-frequent users (<4 visits
      during previous 12-months) and frequent (repeat [4-7 visits], highly frequent [8
      18 visits] and super frequent [>=19 visits]) users in univariate and
      multivariable analyses. RESULTS: Frequent users (2496/65201 [3.8%] patients) were
      more likely to make at least one visit associated with mental health, alcohol, or
      drug-related diagnoses. The proportion of patients with a majority of visits
      related to any of the three diagnoses increased from 5.8% among non-frequent
      users (3616/62705) to 9.4% among repeat users (181/1926), 13.1% among highly
      frequent users (62/473), and 25.8% (25/97 patients) in super frequent users. An
      increasing proportion of visits with alcohol-related diagnoses was observed among
      repeat, highly frequent, and super frequent users but was not found for mental
      health or drug-related complaints. CONCLUSION: Frequent ED users were more likely
      to make a mental health, alcohol or drug-related visit, but a majority of visits
      were only noted for those with alcohol-related diagnoses. To address frequent ED
      use, interventions focusing on managing patients with frequent alcohol-related
      visits may be necessary.

PMID- 24035052
TI  - One-hand chest compression and hands-off time in single-lay rescuer CPR-a manikin
      study.
AB  - PURPOSE: To evaluate the effect of one-hand chest compression while continuously
      maintaining an open airway (OCOA) on rescue breath-associated hands-off time
      (RAHO) during single-lay rescuer cardiopulmonary resuscitation (CPR). METHODS: In
      this study, 193 CPR/automated external defibrillator certified lay rescuers were
      randomly allocated into 2 groups and were tested in a standard scenario using a
      mannequin. In control group (group A), the participants provided standard CPR. In
      group B, OCOA was performed by placing the heel of the strong hand in the center
      of the mannequin's chest while maintaining an open airway using the other hand.
      RESULTS: Mean RAHO was statistically significantly different between the two
      groups (group A: 8.38 +/- 1.97 vs group B: 7.71 +/- 2.43, P = .008). Only 13
      (13.5%) group A and 25 (25.8%) group B providers ventilated the manikin with
      tidal volumes of 500 to 600 mL, while most participants caused hyperventilation.
      Although there were no significant differences in mean tidal volume between the
      groups, stomach inflation was greater in group A (< .001). Chest compressions
      were deeper in group A (P < .001), while chest recoil was significantly better in
      group B. In group B, there was a positive correlation between body mass index and
      compression depth (group A, P = .423; group B, P < .001). CONCLUSIONS: In our
      study, OCOA resulted in shorter RAHO and less stomach inflation. Our results
      indicate that the airway should be maintained open during chest compressions,
      regardless of the technique. Larger studies are needed for the full clarification
      of OCOA.

PMID- 24035053
TI  - Leadership development in the English National Health Service: A counter
      narrative to inform policy.
AB  - OBJECTIVES: To examine the current approach to leadership development in the
      English National Health Service (NHS) and consider its implications for nursing.
      To stimulate debate about the nature of leadership development in a range of
      health care settings. BACKGROUND: Good leadership is central to the provision of
      high quality nursing care. This has focussed attention on the leadership
      development of nurses and other health care staff. It has been a key policy
      concern in the English NHS of late and fostered the growth of leadership
      development programmes founded on competency based approaches. DESIGN: This is a
      policy review informed by the concept of episteme. DATA SOURCES: Relevant policy
      documents and related literature. REVIEW METHODS: Using Foucault's concept of
      episteme, leadership development policy is examined in context and a 'counter
      narrative' developed to demonstrate that current approaches are rooted in
      competency based accounts which constitute a limited, yet dominant narrative.
      CONCLUSION: Leadership takes many forms and varies hugely according to task and
      context. Acknowledging this in the form of a counter narrative offers a
      contribution to more constructive policy development in the English NHS and more
      widely. A more nuanced debate about leadership development and greater diversity
      in the provision of development programmes and activities is required. Leadership
      development has been advocated as being crucial to the advancement of nursing.
      Detailed analysis of its nature and function is essential if it is to meet the
      needs of nurse leaders.

PMID- 24035055
TI  - Re. Pre- and perioperative factors affecting infection after living donor liver
      transplantation.

PMID- 24035054
TI  - Cardiometabolic factors and disease duration in patients with Parkinson's
      disease.
AB  - OBJECTIVE: Previous studies have reported that patients with Parkinson's disease
      (PD) have a favorable cardiometabolic risk profile. The aim of this study was to
      investigate the relationship between cardiometabolic risk factors and the
      duration of disease. METHODS: One hundred and fifty patients with PD (56.7% men)
      were studied, measuring body mass index (BMI), waist circumference (WC), body fat
      percentage (BF%) by impedance, fasting glucose, serum lipids, and transaminases.
      RESULTS: In sex- and age-adjusted correlation models, duration of PD was
      inversely related to BMI (r = -0.20; P < 0.05) and BF% (r = -0.29; P < 0.005).
      Using multivariable regression models (adjustments: age, gender, smoking status,
      levodopa dose and, alternatively, BMI, WC, or BF%), high-density lipoprotein
      (HDL) levels were positively correlated with disease duration (P < 0.01 for all).
      In models adjusted for WC and BF%, total HDL-cholesterol ratio was also inversely
      associated with duration of PD (P < 0.05 for both). No other association between
      biochemical variables and the duration of PD was found. Moreover, no dose
      response effect of levodopa on metabolic risk factors was observed. CONCLUSIONS:
      HDL levels and total HDL-cholesterol ratio were favorably associated with
      duration of PD. This factor may contribute to cardiometabolic protection in PD.
      The mechanisms underlying this association deserve further investigation.

PMID- 24035056
TI  - Porcine placenta mitigates protein-energy malnutrition-induced fatigue.
AB  - OBJECTIVE: Fatigue can be caused by a deficiency of nutrition or immune function.
      The goal of this study was to identify the effects of porcine placenta extract
      (PPE) and its constituents, amino acids (glutamic acid, glycine, arginine, and
      proline), on protein-energy malnutrition (PEM)-induced fatigue. METHODS: Mice
      were administered a PEM diet and came to immunodeficient status. Simultaneously,
      the mice were administered PPE or amino acids and a forced swimming test (FST)
      was performed. We analyzed the levels of fatigue-related factors in serum,
      splenocytes, and muscles. RESULTS: In the FST, PPE or amino acids significantly
      decreased immobility times compared with the PEM diet. PPE or amino acids also
      significantly decreased the serum levels of fatigue-related factors after the
      FST. Additionally, PPE significantly decreased the levels of fatigue-related
      muscle parameters after the FST. In this in vitro study, PPE increased the mRNA
      and protein expression of Ki-67 and promoted the proliferation of splenocytes.
      PPE or amino acids significantly increased the levels of intracellular calcium
      and the translocation into the nucleus of nuclear factor of activated T-cells
      cytoplasmic in stimulated splenocytes. PPE or amino acids significantly decreased
      the production of fatigue-related inflammatory cytokines in the stimulated
      splenocytes. Additionally, the translocated levels of nuclear factor-kappaB in
      the nucleus and the degradation of the inhibitory protein, IkappaBalpha, in the
      cytosol were inhibited by PPE or amino acids. CONCLUSION: These results
      demonstrate that PPE and its constituents regulate PEM-induced fatigue through
      improving levels of immunity and decreasing fatigue-related factors. PPE may be a
      potential agent for a recovery from fatigue.

PMID- 24035057
TI  - Re. Iodine biofortification through plant biotechnology: plant biofortification
      as a potential strategy to address iodine deficiency.

PMID- 24035058
TI  - Automatic temporal lobe atrophy assessment in prodromal AD: Data from the
      DESCRIPA study.
AB  - BACKGROUND: In the framework of the clinical validation of research tools, this
      investigation presents a validation study of an automatic medial temporal lobe
      atrophy measure that is applied to a naturalistic population sampled from memory
      clinic patients across Europe. METHODS: The procedure was developed on 1.5-T
      magnetic resonance images from the Alzheimer's Disease Neuroimaging Initiative
      database, and it was validated on an independent data set coming from the
      DESCRIPA study. All images underwent an automatic processing procedure to assess
      tissue atrophy that was targeted at the hippocampal region. For each subject, the
      procedure returns a classification index. Once provided with the clinical
      assessment at baseline and follow-up, subjects were grouped into cohorts to
      assess classification performance. Each cohort was divided into converters (co)
      and nonconverters (nc) depending on the clinical outcome at follow-up visit.
      RESULTS: We found the area under the receiver operating characteristic curve
      (AUC) was 0.81 for all co versus nc subjects, and AUC was 0.90 for subjective
      memory complaint (SMCnc) versus all co subjects. Furthermore, when training on
      mild cognitive impairment (MCI-nc/MCI-co), the classification performance
      generally exceeds that found when training on controls versus Alzheimer's disease
      (CTRL/AD). CONCLUSIONS: Automatic magnetic resonance imaging analysis may assist
      clinical classification of subjects in a memory clinic setting even when images
      are not specifically acquired for automatic analysis.

PMID- 24035059
TI  - Myofascial involvement of supra- and infraspinatus muscles contributes to
      ipsilateral shoulder pain after muscle-sparing thoracotomy and video-assisted
      thoracic surgery.
AB  - OBJECTIVE: This study examined the hypothesis that ipsilateral upper extremity
      elevation for muscle-sparing thoracotomy procedures contributes to the
      postoperative shoulder pain. DESIGN: Prospective observational study. SETTING:
      Medical center. PARTICIPANTS: ASA physical status 1-2 patients undergoing
      elective lung surgeries including pneumonectomy, lobectomy, and segmentectomy
      performed through either the anterolateral approach or video-assisted thoracotomy
      surgery. INTERVENTIONS: Postoperative observation of ipsilateral shoulder pain.
      MEASUREMENTS AND MAIN RESULTS: Postoperative examinations of sites of shoulder
      pain (clavicle, anterior, lateral,or posterior aspect of acromion, posterior
      neck, supraspinatus, infraspinatus, and these entire areas) with or without
      trigger points, visual analog scale score of wound pain, and requested counts of
      analgesics. The number of patients who suffered from postoperative shoulder pain
      was 37 of 70 (52.9%). Demographic data, anterolateral/VATS ratio, VAS scores, and
      requested counts of rescue analgesics requirement were similar in the groups of
      patients with and without postoperative shoulder pain. The segmentectomy caused a
      significantly higher incidence of postoperative shoulder pain compared with other
      procedures (p < 0.05). The supra- and infraspinatus were significantly higher
      areas of painful regions compared to the other sites. The 16 of 37 patients
      (43.2%) with shoulder pain showed defined trigger points in their painful areas.
      CONCLUSION: These results supported the hypothesis that myofascial involvement
      contributed, to some extent, to shoulder pain after muscle-sparing thoracotomy
      with ipsilateral upper extremity elevation.

PMID- 24035060
TI  - Changes in microcirculatory perfusion and oxygenation during cardiac surgery with
      or without cardiopulmonary bypass.

PMID- 24035061
TI  - Acute obstruction of craniocervical venous drainage in a lung-transplant patient.

PMID- 24035062
TI  - Survey of thoracic anesthetic practice in Italy.
AB  - OBJECTIVE: The object of this study was to conduct and analyze the output of a
      survey involving a cohort of all Italian hospitals performing thoracic surgery to
      gather data on anesthetic management, one-lung ventilation (OLV) management, and
      post-thoracotomy pain relief in thoracic anesthesia. DESIGN: Survey. SETTING:
      Italy. PARTICIPANTS: An invitation to participate in the survey was e-mailed to
      all the members of the Italian Society of Anesthesia and Intensive Care Medicine.
      INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: A total of 62 responses were
      received from 47 centers. The key findings were: Double-lumen tube is still the
      first choice lung separation technique in current use; pressure-controlled
      ventilation and volume-controlled ventilation modes are homogenously distributed
      across the sample and, a tidal volumes (VT) of 4-6 mL/kg during OLV was preferred
      to all others; moderate or restrictive fluid management were the most used
      strategies of fluid administration in thoracic anesthesia; thoracic epidural
      analgesia represented the "gold standard" for post-thoracotomy pain relief in
      combination with intravenous analgesia. CONCLUSION: The results of this survey
      showed that Italian anesthesiologist follow the recommended standard of care for
      anesthetic management during OLV.

PMID- 24035063
TI  - Thoracic paravertebral nerve block as the sole anesthetic for an open biopsy of a
      large anterior mediastinal mass.

PMID- 24035064
TI  - Effects of isoflurane anesthesia on aortic compliance and systemic hemodynamics
      in compliant and noncompliant aortas.
AB  - OBJECTIVES: To investigate the effect of general anesthesia on aortic compliance
      and other cardiovascular hemodynamics in chronically instrumented pigs with
      compliant and noncompliant (stiff) aortas. DESIGN: Experimental study. SETTING:
      University animal laboratory. PARTICIPANTS: Twelve adult Yucatan miniature pigs.
      INTERVENTIONS: Chronic instrumentation of a compliant (control; n = 7) and
      noncompliant (n = 5) group to measure pressure and flow in the ascending aorta. A
      Teflon prosthesis was wrapped around the aorta (noncompliant group) to limit wall
      compliance. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were recorded
      on the 15th postoperative day, both awake and after general anesthesia. Banding
      the aorta caused a significant decrease in arterial compliance (-49%, p<0.001)
      and increases in systolic blood pressure (SBP: +38%, p = 0.001) and pulse
      pressure (+107%, p< 0.01). Induction of anesthesia in the control group produced
      a 15% increase in arterial compliance (p<0.05), resulting in a subtle decrease in
      SBP (-12%), diastolic blood pressure (DBP; -13%) and mean blood pressure (MBP; 
      12%). Induction of anesthesia in the noncompliant group also caused a significant
      increase in arterial compliance (17%, p<0.001), but caused significant decreases
      in SBP (21%, p<0.01), DBP (23%, p<0.01) and MBP (22%, p<0.01) as compared with
      controls. CONCLUSIONS: Induction of general anesthesia caused a similar increase
      in total arterial compliance and was associated with a decrease in SBP that was
      more pronounced in animals with noncompliant aortas. These results indicated that
      anesthesia caused a greater hemodynamic effect on noncompliant (stiff) aortas and
      may explain the extensive hemodynamic fluctuation and instability often observed
      in atherosclerotic, elderly patients with stiff aortas.

PMID- 24035065
TI  - Anesthetic implications for patients with Swyer-James syndrome.
AB  - OBJECTIVE: The aim of this study was to describe the anesthetic management and
      perioperative outcomes in patients with Swyer-James syndrome (SJS), a rare
      acquired pulmonary disorder caused by postinfectious bronchiolitis obliterans
      resulting in airway obstruction and focal areas of emphysema or bronchiectasis.
      DESIGN: A retrospective computerized search of the medical records database at a
      large academic tertiary referral center was performed for patients with SJS from
      January 1, 2001 through July 31, 2012 who underwent procedures requiring
      anesthesia. A review of the perioperative course in the SJS patients as well as
      in those identified by a literature search was performed. SETTING: Academic
      tertiary referral center, both inpatient and outpatient settings. PARTICIPANTS:
      Patients with a diagnosis of SJS. INTERVENTIONS: No interventions were performed.
      MEASUREMENTS AND MAIN RESULTS: The authors identified 4 patients with SJS who
      underwent 7 uneventful anesthetics including one lung resection. Three patients
      were symptomatic preoperatively. The literature review identified 23 SJS patients
      who underwent lung resection for recurrent pulmonary symptoms. One patient
      developed hypoxemia during one-lung ventilation. Three patients had a prolonged
      hospital stay (>=10 days). All patients undergoing lung resection were young
      (<=42 years of age). CONCLUSION: Though SJS may be an incidental finding, these
      patients may have marked symptomatology, recurrent pulmonary infections, and
      pneumothoraces that may require lung resection. The patients tolerated anesthesia
      well. In severe SJS cases, pulmonary pathology and perioperative management
      strategies parallel that of patients with severe obstructive pulmonary disease.

PMID- 24035066
TI  - Incidence of acute myocardial infarction in first and second generation minority
      groups: does the second generation converge towards the majority population?
AB  - BACKGROUND: Differences in acute myocardial infarction (AMI) incidence between
      ethnic minority and migrant groups (henceforth, minority groups) and the majority
      population have been reported. Health differences may converge towards the
      majority population over generations. We assessed whether AMI incidence
      differences between minority groups living in the Netherlands and the Dutch
      majority population exist, and whether the incidence converges towards the
      majority population over generations. METHODS: A nationwide register-based cohort
      study was conducted from 1997 to 2007. Using Cox Proportional Hazard Models AMI
      incidence differences between minorities and the majority population were
      estimated. When possible, analyses were stratified by generation. RESULTS: AMI
      incidence differences between minorities and the majority population depended on
      the country of origin, and often varied between minorities originating from the
      same geographical region. For example, among North African and Mediterranean
      minorities, incidence was higher in Turkish (Hazard Ratio (HR): 1.34; 95%
      Confidence Interval (95% CI): 1.28-1.41), but lower in Moroccans (HR: 0.46; 95%
      CI: 0.40-0.52) compared with the majority population. Most minorities had a
      similar or lower incidence than the majority population, which remained similar
      or converged towards the incidence of the majority population over generations.
      In contrast, among minorities from the former Dutch colonies (Suriname,
      Indonesia, Netherlands Antilles) beneficial intergenerational changes were
      observed. CONCLUSIONS: Health care professionals and policy makers should be
      aware of substantial AMI incidence differences between minority groups and the
      majority population, and the often unbeneficial change over generations. Future
      research should be cautious when clustering minority groups based on geographical
      region of the country of origin.

PMID- 24035067
TI  - Perspectives of family members on planning end-of-life care for terminally ill
      and frail older people.
AB  - CONTEXT: Advance care planning (ACP) is the process by which patients, together
      with their physician and loved ones, establish preferences for future care.
      Because previous research has shown that relatives play a considerable role in
      end-of-life care decisions, it is important to understand how family members are
      involved in this process. OBJECTIVES: To gain understanding of the involvement of
      family members in ACP for older people near the end of life by exploring their
      views and experiences concerning this process. METHODS: This was a qualitative
      research study, done with semistructured interviews. Twenty-one family members
      were recruited from three geriatric settings in Flanders, Belgium. The data were
      analyzed using the constant comparative method as proposed by the grounded
      theory. RESULTS: Family members took different positions in the ACP process
      depending on how much responsibility the family member wanted to take and to what
      extent the family member felt the patient expected him/her to play a part. The
      position of family members on these two dimensions was influenced by several
      factors, namely acknowledgment of the imminent death, experiences with death and
      dying, opinion about the benefits of ACP, burden of initiating conversations
      about death and dying, and trust in health care providers. Furthermore, the role
      of family members in ACP was embedded in the existing relationship patterns.
      CONCLUSION: This study provides insight into the different positions of family
      members in the end-of-life care planning of older patients with a short life
      expectancy. It is important for health care providers to understand the position
      of a family member in the ACP of the patient, take into account that family
      members may experience an active role in ACP as burdensome, and consider existing
      relationship patterns.

PMID- 24035068
TI  - A longitudinal analysis of symptom clusters in cancer patients and their
      sociodemographic predictors.
AB  - CONTEXT: Exploring the relationships between concurrent symptoms or "symptom
      clusters" (SCs) longitudinally may complement the knowledge gained from the
      traditional approach of examining individual symptoms or SCs crosssectionally.
      OBJECTIVES: To identify consistent SCs over the course of one year and determine
      the possible associations between SCs and demographic and medical
      characteristics, and between SCs and emotional distress. METHODS: This study was
      an exploratory longitudinal analysis of SCs in a large sample of newly diagnosed
      cancer patients. Patients provided symptom assessment data at baseline, three,
      six, and 12 months. A factor analysis was conducted (controlling for the patient
      over time) on pain, fatigue, anxiety, depression, sleep, weight change, and food
      intake items to identify clusters. A panel regression on each cluster explored
      associations with demographic and medical characteristics and distress. RESULTS:
      In total, 877 patients provided baseline data, with 505 retained at 12 months.
      Three SCs explained 71% of the variance. The somatic cluster included pain,
      fatigue, and sleep; the psychological cluster included anxiety and depression;
      and the nutrition cluster consisted of weight and food intake. Low income and
      treatment with radiation or chemotherapy predicted higher somatic symptom burden.
      Younger age, being female, low income, and treatment with surgery predicted more
      psychological symptomatology. Older age and treatment with surgery predicted
      higher nutritional burden. Patients with higher somatic, psychological, and
      nutritional symptom burden reported higher distress. CONCLUSION: The presence of
      SCs across the first year of diagnosis supports the need for routine and ongoing
      screening for the range of symptoms that may be experienced by patients. Further
      work is needed to develop interventions that better target individual symptoms
      that cluster, as well as the entire cluster itself.

PMID- 24035069
TI  - Contending with advanced illness: patient and caregiver perspectives.
AB  - CONTEXT: Despite improvements in end-of-life care, some unrelieved suffering
      persists for patients with advanced illness and their family members. Hospice and
      palliative care services can reduce suffering, but these services remain under
      used. OBJECTIVES: To investigate how patients with advanced illness and their
      primary caregivers experienced and responded to health care needs and decision
      making and how some dyads moved toward comfort-focused care. METHODS: This was a
      qualitative study using the grounded theory method for sample selection, data
      collection, and analysis. Dyadic semi-structured interviews were audio-recorded
      and transcribed for analysis. Twenty-two participants, 12 patients and 10 family
      surrogates, provided 16 interviews for this study. RESULTS: Participants engaged
      in a process of contending with advanced illness. The major phases comprising
      this process were suffering, struggling, and settling. Struggling included
      enduring the experience and fighting the illness. During the phase of settling,
      the focus shifted away from curative efforts and toward supportive care.
      Conditions that facilitated the movement into this phase included receiving clear
      and consistent information about the patient's health status, trusting health
      care providers, having attended to advance care planning in some form, and being
      aware of and able to acknowledge the terminal nature of the illness. CONCLUSION:
      Findings from this pilot study offer a preliminary theoretical model to enhance
      the understanding of patient and family caregiver needs during advanced illness.
      Awareness of their perspective can inform the timing and content of clinicians'
      communication and interventions.

PMID- 24035070
TI  - The use of octreotide to manage symptoms of bronchorrhea: a case report.
AB  - Octreotide, a synthetic analogue of the hormone somatostatin, is primarily used
      in palliative medicine because of its antisecretory effect and has been shown to
      be effective in the management of bowel obstruction, nausea, and diarrhea.
      Octreotide also has been successfully used for the management of bronchorrhea in
      both inpatient and outpatient settings. We report the case of a 47-year-old
      female with a history of bronchioloalveolar cell carcinoma whose copious
      bronchial secretions were controlled with octreotide. Octreotide should be
      further evaluated as a first-line treatment for bronchorrhea. 

PMID- 24035072
TI  - A prospective CBCT study of upper airway changes after rapid maxillary expansion.
AB  - OBJECTIVE: The aim of this prospective study was to investigate the upper airway
      changes after rapid maxillary expansion utilizing CBCT. METHODS: 16 children (10
      male, 6 female) with a mean age of 12.73 +/- 1.73 years underwent RME as part of
      their comprehensive orthodontic treatment with4,6-banded hyrax expanders. The
      screws were activated 2 turns a day. Depending on the expansion amount (2.7
      6.3mm), the activation period ranged from 2 to 3 weeks. CBCT images were taken
      immediately before (T1) and three months after expansion (T2) in upright
      position, with patients' heads kept in consistent position. All CBCT data were
      processed with the software EZ3D2009. After orienting the CBCT images, a set of
      linear, area and volumetric parameters of the upper airway were measured and
      calculated. Student paired t test and one-way ANOVA were applied. The
      significance level of P<0.0033 was used according to the Bonferroni correction.
      RESULTS: After expansion, with molar-to-molar width increasing 4.4 +/- 1.3 mm and
      molars tipping 6.2 +/- 6.2 degrees , the nasal floor width and nasal lateral
      width increased 1.6, 1.5, and 1.6mm and 1.3, 1.7, and 1.4mm from the anterior to
      the posterior part, respectively. And there was no difference among the anterior,
      median and posterior part. The lower nasal volume increased 1348.5mm(3) with the
      percentage change being 8.1%. The pharyngeal airway showed no positive change.
      CONCLUSION: RME can expand the nasal cavity and the expansion pattern may follow
      the parallel opening configuration. However, the influence on the pharyngeal
      airway is limited.

PMID- 24035073
TI  - Genome sequencing for healthy individuals.
AB  - Genome sequencing of healthy individuals has the potential to lead to improved
      well-being and disease prevention, but numerous challenges remain that must be
      addressed to realize these benefits and, importantly, these benefits must be
      equitable across society. 

PMID- 24035074
TI  - Prevention of incisional hernias: how to close a midline incision.
AB  - The development of wound complications is closely related to the surgical
      technique at wound closure. The risk of the suture technique affecting the
      development of wound dehiscence and incisional hernia can be monitored through
      the suture length to wound length ratio. Midline incisions should be closed in
      one layer by a continuous-suture technique using a monofilament suture material
      tied with self-locking knots. Excessive tension should not be placed on the
      suture. Closure must always be with a suture length to wound length ratio higher
      than 4. 

PMID- 24035071
TI  - Decisional control preferences, disclosure of information preferences, and
      satisfaction among Hispanic patients with advanced cancer.
AB  - CONTEXT: Studies to determine the decisional control preferences (DCPs) in
      Hispanic patients receiving palliative care are limited. OBJECTIVES: The aims of
      this study were to describe DCPs, disclosure of information, and satisfaction
      with decision making among Hispanics and to determine the degree of concordance
      between patients' DCPs and their self-reported decisions. METHODS: We surveyed
      387 cancer patients referred to outpatient palliative care clinics in Argentina,
      Chile, Guatemala, and the U.S. DCPs were measured with the Control Preference
      Scale, disclosure preferences with the Disclosure of Information Preferences
      questionnaire, and satisfaction with care with the Satisfaction with Decision
      Scale. RESULTS: In this study, 182 patients (47.6%) preferred shared decisional
      control, 119 (31.2%) preferred active decisional control, and 81 (21.2%)
      preferred a passive approach. Concerning their diagnosis and prognosis, 345 (92%)
      patients wanted to know their diagnosis, and 355 (94%) wanted to know their
      prognosis. Three hundred thirty-seven (87%) patients were satisfied with the
      decision-making process. DCPs were concordant with the self-reported decision
      making process in 264 (69%) patients (weighted kappa = 0.55). Patients' greater
      satisfaction with the decision-making process was correlated with older age (P <=
      0.001) and with a preference for enhanced diagnostic disclosure (P <= 0.024).
      Satisfaction did not correlate with concordance in the decision-making process.
      CONCLUSION: The vast majority preferred a shared or active decision-making
      process and wanted information about their diagnosis and prognosis. Older
      patients and those who wanted to know their diagnosis seemed to be more satisfied
      with the way treatment decisions were made.

PMID- 24035075
TI  - Preoperative risk reduction: strategies to optimize outcomes.
AB  - The success of hernia repair is measured by absence of recurrence, appearance of
      the surgical scar, and perioperative morbidity. Perioperative surgical site
      occurrence (SSO), defined as infection, seroma, wound ischemia, and dehiscence,
      increases the risk of recurrent hernia by at least 3-fold. The surgeon should
      optimize all measures that promote healing, reduce infection, and enhance early
      postoperative recovery. In the population with ventral hernia, the most common
      complication in the immediate perioperative period is surgical site infection.
      This article reviews several preoperative measures that have been reported to
      decrease SSOs and shorten length of hospital stay. 

PMID- 24035076
TI  - Repair of umbilical and epigastric hernias.
AB  - Umbilical and epigastric hernias are primary midline defects that are present in
      up to 50% of the population. In the United States, only about 1% of the
      population carries this specific diagnosis, and only about 11% of these are
      repaired. Repair is aimed at symptoms relief or prevention, and the patient's
      goals and expectations should be explicitly identified and aligned with the
      health care team. This article details some relevant and interesting anatomic
      issues, reviews existing data, and highlights some common and important surgical
      techniques. Emphasis is placed on a patient-centered approach to the repair of
      umbilical and epigastric hernias. 

PMID- 24035077
TI  - Laparoscopic ventral hernia repair.
AB  - Laparoscopic ventral hernia repair (LVHR) has established itself as a well
      accepted option in the treatment of hernias. Clear benefits have been established
      regarding the superiority of LVHR in terms of fewer wound infections compared
      with open repairs. Meticulous technique and appropriate patient selection are
      critical to obtain the reported results. 

PMID- 24035078
TI  - Open ventral hernia repair with component separation.
AB  - In this article, the authors describe their current operative technique for open
      ventral hernia repair using component separation. Although methods of anterior
      component separation are described, in their current practice, the authors
      primarily use posterior component separation with transversus abdominis release
      to permit dissection beyond the retrorectus space. This method adheres to the
      literature-supported principles of a tension-free midline fascial closure with
      wide mesh overlap of mesh positioned in a sublay position. The authors'
      experience with this method supports a low recurrence rate and reduced wound
      morbidity. 

PMID- 24035079
TI  - Atypical hernias: suprapubic, subxiphoid, and flank.
AB  - Thorough knowledge of anatomy, appropriate preoperative planning, and reliance on
      the principles of hernia repair ensure successful outcomes. There are many
      options for repair, including technique and mesh choice. The hernia surgeon
      should be well versed in the open and laparoscopic approaches and apply them
      based on the individual clinical presentation. Long-term outcomes related to
      suprapubic, subxiphoid, and lateral hernia repairs are limited; however, open and
      laparoscopic repairs using wide mesh overlap and adequate fixation have
      acceptable outcomes and recurrence rates. Future research will likely focus on
      comparative studies based on patient factors, techniques, mesh, and cost. 

PMID- 24035080
TI  - Takedown of enterocutaneous fistula and complex abdominal wall reconstruction.
AB  - Key steps in managing patients with enterocutaneous fistulation and an abdominal
      wall defect include dealing effectively with abdominal sepsis and providing safe
      and effective nutritional support and skin care, then assessing intestinal and
      abdominal anatomy, before undertaking reconstructive surgery. The complexity,
      cost, and morbidity associated with such cases justifies creation of specialized
      centers in which gastroenterologic, hernia, and plastic surgical expertise, as
      well as experienced wound and stoma nursing and nutritional and psychological
      support, can be made available for patients with these challenging problems. 

PMID- 24035081
TI  - Parastomal hernia repair.
AB  - Occurrence of parastomal hernia is considered a near inevitable consequence of
      stoma formation, making their management a common clinical dilemma. This article
      reviews the outcomes of different surgical approaches for hernia repair and
      describes in detail the laparoscopic Sugarbaker technique, which has been shown
      to have lower recurrence rates than other methods. Also reviewed is the current
      literature on the impact of prophylactic mesh placement during ostomy formation. 

PMID- 24035082
TI  - Soft tissue coverage in abdominal wall reconstruction.
AB  - Abdominal wall defects requiring soft tissue coverage can be either partial
      thickness defects or full-thickness composite defects. Soft tissue flap
      reconstruction offers significant advantages in defects that cannot be closed
      primarily. Flap reconstruction is performed in a single-stage procedure obviating
      chronic wound management. If the defect size exceeds the availability of local
      soft tissue for coverage, regional pedicled flaps can be delivered into the
      abdominal wall while maintaining blood supply from their donor site.
      Microsurgical free tissue transfer increases the capacity to provide soft tissue
      coverage for abdominal wall defects that are not amenable to either local or
      regional flap coverage. 

PMID- 24035083
TI  - Biology of biological meshes used in hernia repair.
AB  - Successful repair of most hernias requires the use of a prosthetic implant for
      reinforcement of the defect. Because of the need for prosthetic implants to
      resist infections as well to support repairs in contaminated or potentially
      contaminated fields, biological meshes have been developed to take the place of
      nondegradable synthetic meshes in cases where mesh infection is of high concern.
      The ideal is a biological matrix that resists infection while providing durable
      reinforcement of a hernia repair. This article reviews the validity of
      assumptions that support the purported notion of the biological behavior of
      biological meshes. 

PMID- 24035084
TI  - Clinical outcomes of biologic mesh: where do we stand?
AB  - After review and evaluation of current clinical data, including significant wound
      complications, a noteworthy failure rate at 1 year, and high product costs, it is
      difficult to support the continued use of biologic meshes in incisional hernia
      repair outside of well-designed and rigorously conducted clinical trials. An
      industry-sponsored, publicly available registry of biologic prosthetic use for
      ventral hernia repairs is needed. This straightforward mandate, if properly
      constructed and implemented, would significantly expand knowledge regarding how
      these intriguing biomaterials are used and their overall clinical efficacy, thus
      yielding a more robust basis for the continued use of biologic prosthetics in
      hernia repair than is currently available. 

PMID- 24035085
TI  - Safety of prosthetic mesh hernia repair in contaminated fields.
AB  - For years, surgical dictum has posited that permanent synthetic mesh is
      contraindicated in the repair of a hernia in a contaminated field. Numerous
      investigators, however, have demonstrated the acceptably low morbidity associated
      with the use of heavy-weight polypropylene mesh in clean-contaminated and
      contaminated fields. Recently, experience utilizing more modern, light-weight
      polypropylene mesh constructs in contaminated fields has grown considerably. The
      time has come to critically reevaluate the unfounded fear of utilizing permanent
      synthetic mesh in contaminated fields, as we will review the data speaking to the
      safety of mesh in these contaminated fields. 

PMID- 24035086
TI  - Economics of abdominal wall reconstruction.
AB  - The economic aspects of abdominal wall reconstruction are frequently overlooked,
      although understandings of the financial implications are essential in providing
      cost-efficient health care. Ventral hernia repairs are frequently performed
      surgical procedures with significant economic ramifications for employers,
      insurers, providers, and patients because of the volume of procedures,
      complication rates, the significant rate of recurrence, and escalating costs.
      Because biological mesh materials add significant expense to the costs of
      treating complex abdominal wall hernias, the role of such costly materials needs
      to be better defined to ensure the most cost-efficient and effective treatments
      for ventral abdominal wall hernias. 

PMID- 24035087
TI  - Pediatric abdominal wall defects.
AB  - This article reviews the incidence, presentation, anatomy, and surgical
      management of abdominal wall defects found in the pediatric population. Defects
      such as inguinal hernia and umbilical hernia are common and are encountered
      frequently by the pediatric surgeon. Recently developed techniques for repairing
      these hernias are aimed at improving cosmesis and decreasing pain while
      maintaining acceptably low recurrence rates. Less common conditions such as
      femoral hernia, Spigelian hernia, epigastric hernia, lumbar hernia,
      gastroschisis, and omphalocele are also discussed. The surgical treatment of
      gastroschisis and omphalocele has undergone some advancement with the use of
      various silos and meshes. 

PMID- 24035088
TI  - Laparoscopic versus open inguinal hernia repair.
AB  - The laparoscopic approach to inguinal hernia surgery is safe and reliable. It has
      a similar recurrence rate as open tension-free mesh repair. Because the
      laparoscopic approach has less chronic postoperative pain and numbness, fast
      return to normal activities, and decreased incidence of wound infection and
      hematoma, it should be considered an appropriate approach for inguinal hernia
      surgery. These results can be achieved if a surgeon is proficient in the
      technique, has a clear understanding of the anatomy, and performs it on a regular
      basis. This article focuses on questions related to laparoscopic inguinal hernia
      surgery and provides answers based on published literature. 

PMID- 24035089
TI  - Abdominal wall reconstruction.

PMID- 24035090
TI  - Abdominal wall reconstruction.

PMID- 24035091
TI  - From cell to organism across space and time.

PMID- 24035092
TI  - Identification of new inhibitors for low molecular weight protein tyrosine
      phosphatase isoform B.
AB  - The National Cancer Institute Diversity Set II (1356 compounds) and Diversity Set
      III (1597 compounds) were screened via in silico methods as potential inhibitors
      of low molecular weight protein tyrosine phosphatase (LWM-PTP) isoform B (EC
      3.1.3.48). Those candidates that demonstrated comparable or better docking scores
      than that of pyridoxal 5'-phosphate (PLP), one of the most potent known
      inhibitors of LMW-PTP with a competitive inhibitor dissociation constant (Kis) of
      7.6MUM (pH 5.0), were analyzed via in vitro kinetic assays against LMW-PTP
      isoform B. While none of the compounds tested in vitro was significantly better
      that PLP, five compounds showed comparable inhibition. These five compounds are
      very diverse in structure and represent new therapeutic leads for inhibition of
      this isozyme. 

PMID- 24035093
TI  - Safe and easy route for the synthesis of 1,3-dimethyl-1,2,3-triazolium salt and
      investigation of its anticancer activities.
AB  - We have developed a new safe and easy route for the synthesis of 1,3-dimethyl
      1,2,3-triazolium derivatives. We have reported the synthesis of 4,9-dioxo-1,3
      dimethylnaphtho[2,3-d][1,2,3]triazol-3-ium chloride from methylation of 1-methyl
      1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione. The synthesis of 1-methyl-1H
      naphtho[2,3-d][1,2,3]triazole-4,9-dione is inefficient as a significant amount of
      by-product is formed that is difficult to separate and also unsafe as it requires
      the use of hazardous methylazide as a starting material. It is, however,
      important to develop an improved method for the synthesis of 4,9-dioxo-1,3
      dimethylnaphtho[2,3-d][1,2,3]triazol-3-ium salt due to its significant anticancer
      activities. Herein, we report a safe and convenient route for the synthesis of
      this compound, which lead to more detailed exploration of its profound anticancer
      activities. The improved method can be applicable for the synthesis of other 1,3
      dimethyl-1,2,3-triazolium salts of interest without the use of potentially
      explosive methylazide. The compound synthesized in this new method shows
      significant anticancer activities against melanoma, colon cancer, non-small cell
      lung cancer and central nervous system (CNS) cancer with GI50 values ranging from
      low MUM to nM. 

PMID- 24035094
TI  - Benzohydroxamic acids as potent and selective anti-HCV agents.
AB  - A diverse collection of 40 derivatives of benzohydroxamic acid (BHAs) of various
      structural groups were synthesized and tested against hepatitis C virus (HCV) in
      full-genome replicon assay. Some of these compounds demonstrated an exceptional
      activity, suppressing viral replication at sub-micromolar concentrations. The
      compounds were inactive against key viral enzymes NS3, and NS5B in vitro assays,
      suggesting host cell inhibition target(s). The testing results were consistent
      with metal coordination by the BHAs hydroxamic group in complex with a target(s).
      Remarkably, this class of compounds did not suppress poliomyelitis virus (PV)
      propagation in RD cells indicating a specific antiviral activity of BHAs against
      HCV. 

PMID- 24035095
TI  - Chiral cationic polyamines for chiral microcapsules and siRNA delivery.
AB  - Reported herein is the use of chiral cationic polyamines for two intriguing
      applications: fabrication of chiral covalently-linked microcapsules, and
      enantiospecific delivery of siRNA to Huh 7 cells. The microcapsules are easily
      fabricated from homochiral polymers, and the resulting architectures can be used
      for supramolecular chiral catalysis and many other potential applications.
      Enantiospecific delivery of siRNA to Huh 7 cells is seen by one 'enantiomer' of
      the polymers delivering siRNA with significantly improved transfection efficiency
      and reduced toxicity compared to the 'enantiomeric' polymer and commercially
      available transfection reagents. Taken together, the use of these easily
      accessible polyamine structures for diverse applications is highlighted in this
      Letter herein and can lead to numerous future research efforts. 

PMID- 24035096
TI  - Chemical investigation of an antimalarial Chinese medicinal herb Picrorhiza
      scrophulariiflora.
AB  - An antimalarial medicinal plant Picrorhiza scrophulariiflora was chemically
      investigated as part of our ongoing research in traditional chinese medicines
      (TCM). Mass directed fractionation of the active part of the crude extract led to
      the isolation of ten main components, three new compounds (1-3) and seven known
      compounds (4-10). Compound 10 inhibited the growth of the Plasmodium falciparum
      3D7 malarial parasite line, with an IC50 value of 8.3MUM. This compound accounted
      for ~95% of P. falciparum growth inhibitory activity in the crude extract
      confirming, for this TCM, that a single compound was responsible for the
      antimalarial activity. 

PMID- 24035097
TI  - Imidazopyridazines as potent inhibitors of Plasmodium falciparum calcium
      dependent protein kinase 1 (PfCDPK1): Preparation and evaluation of pyrazole
      linked analogues.
AB  - The structural diversity and SAR in a series of imidazopyridazine inhibitors of
      Plasmodium falciparum calcium dependent protein kinase 1 (PfCDPK1) has been
      explored and extended. The opportunity to further improve key ADME parameters by
      means of lowering logD was identified, and this was achieved by replacement of a
      six-membered (hetero)aromatic linker with a pyrazole. A short SAR study has
      delivered key examples with useful in vitro activity and ADME profiles, good
      selectivity against a human kinase panel and improved levels of lipophilic ligand
      efficiency. These new analogues thus provide a credible additional route to
      further development of the series. 

PMID- 24035098
TI  - No phoenix will arise from the ashes.

PMID- 24035099
TI  - Differential contribution of mineralocorticoid and glucocorticoid receptors to
      memory formation during sleep.
AB  - Corticosteroids are known to modulate the consolidation of memories during sleep,
      specifically in the hippocampus-dependent declarative memory system. However,
      effects of the major human corticosteroid cortisol are conveyed via two different
      receptors, i.e., mineralocorticoid (MRs) and glucocorticoid receptors (GRs) whose
      specific contributions to memory consolidation are unclear. Whereas a shift in
      the balance between MR and GR activation toward predominant GR activation has
      been found to impair sleep-dependent consolidation of declarative memories, the
      effect of predominant MR activation is not well characterized. Here, we examined
      differential corticosteroid receptor contributions to memory consolidation during
      post-learning sleep in two placebo-controlled double-blind studies in humans, by
      comparing the effects of the selective MR agonist fludrocortisone (0.2 mg,
      orally, Study 1) and of hydrocortisone (22 mg, intravenously, Study 2) with
      strong binding affinity to both MR and GR. We hypothesized increased activation
      of MRs during sleep to enhance declarative memory consolidation, but the joint
      MR/GR activation to impair it. Participants (16 men in each study) learned a
      declarative (word pair associates) and a procedural task (mirror tracing) before
      a 7-h period of nocturnal retention sleep, with the substances administered
      before sleep (Study 1) and during sleep (Study 2), respectively. As hypothesized,
      retention of word pairs, but not of mirror tracing skill, was selectively
      enhanced by the MR agonist fludrocortisone. An impairing effect of hydrocortisone
      on word pair retention remained non-significant possibly reflecting that
      hydrocortisone administration failed to establish robust predominance of GR
      activation. Our results show that predominant MR activation benefits declarative
      memory consolidation presumably by enhancing the sleep-dependent reactivation of
      hippocampal memories and resultant synaptic plastic processes. The effect is
      counteracted by additional GR activation. Insufficient MR activation, like GR
      overactivation, might be a factor contributing to memory impairment in
      pathological conditions.

PMID- 24035100
TI  - Induction of apoptosis and inhibition of invasion in choriocarcinoma JEG-3 cells
      by alpha-calendic acid and beta-calendic acid.
AB  - Alfa-calendic acid and beta-calendic acid, geometric and positional isomers of
      linolenic acid were previously shown to possess potent anticancer properties. In
      this study, we found that alpha-calendic acid and beta-calendic acid could induce
      apoptosis and suppress invasion of human choriocarcinoma JEG-3 cells in vitro.
      Treatment with alpha-calendic acid and beta-calendic acid significantly increased
      oxidative stress in human choriocarcinoma JEG-3 cells detected by the level of
      reactive oxygen species (ROS), lipid peroxidation production malondialdehyde
      (MDA), glutathione (GSH) and the effects of antioxidants NAC and alpha
      tocopherol. Furthermore, oxidative stress activated the phosphorylation of
      p38MAPK. SB203580, a selective p38MAPK inhibitor, blocked the apoptosis induced
      by alpha-calendic acid and beta-calendic acid by upregulating Bcl-2/Bax ratio and
      inhibition of the activation of Caspase-3 and Caspase-9. SB20350 also partially
      abrogated the cell invasion effects of alpha-calendic acid and beta-calendic
      acid. These results suggested that alpha-calendic acid and beta-calendic acid
      induced apoptosis and inhibited invasion in JEG-3 cells by activation of
      oxidative stress pathways and subsequent activation of P38MAPK. 

PMID- 24035101
TI  - Atlas of Variations in Medical Practice in Spain: the Spanish National Health
      Service under scrutiny.
AB  - Early in the 2000s, a countrywide health services research initiative was
      launched under the acronym of Atlas VPM: Atlas of Variations in Medical Practice
      in the Spanish National Health System. This initiative aimed at describing
      systematic and unwarranted variations in medical practice at geographic level
      building upon the seminal experience of the Dartmouth Atlas of Health Care. The
      paper aims at explaining the Spanish Atlas experience, built upon the pioneer
      Dartmouth inspiration. A few selected examples will be used along the following
      sections to illustrate the outlined conceptual framework, the different factors
      that may affect variation, and some methodological challenges. 

PMID- 24035102
TI  - Response of QT interval in methadone maintenance treated patients to the rapid
      changes in heart rate provoked by brisk standing: comparison to healthy controls
      and patients with long QT syndrome.
AB  - BACKGROUND: Patients on methadone maintenance therapy are somehow similar to
      patients with congenital long QT syndrome (LQTS) because they have malfunction of
      potassium channels caused by a drug that cannot be easily discontinued. We tested
      patients on methadone therapy with the "stand-up" test, which has been shown to
      unravel pathologic QT-prolongation in congenital long-QT patients. METHODS:
      "Stand-up" test results of methadone-users, healthy volunteers and congenital
      LQTS patients were compared. Methadone serum levels and doses were collected. The
      prognostic value of the test was evaluated after 4 years of follow-up. RESULTS:
      The QT-response of methadone-users to the "stand-up" test resembled that of
      healthy volunteers more than the response of LQTS-patients. Differences in the
      QTc of methadone treated patients and controls, which were statistically
      significant at baseline, became no longer significant after standing. Within 52
      months of follow-up, one patient had suffered unexplained death and one had
      documented ventricular tachycardia. CONCLUSIONS: The QT-response of methadone
      users to the "stand-up" test is similar to that of healthy volunteers, not to
      that of LQTS-patients.

PMID- 24035103
TI  - Fracture and migration of Celect inferior vena cava filters: a retrospective
      review of 741 consecutive implantations.
AB  - PURPOSE: To determine the incidence of fracture and migration of the Celect
      inferior vena cava (IVC) filter at a single tertiary-care center. MATERIALS AND
      METHODS: Images obtained after placement of Celect IVC filters between August
      2007 and January 2013 were retrospectively reviewed for evidence of device
      fracture and migration. The probability of filter fracture at 6 and 12 months
      after filter placement was estimated, and a 95% upper confidence bound was
      constructed. RESULTS: A total of 741 consecutive Celect filters were placed, and
      the following studies were subsequently evaluated: 301 abdominal radiographs, 282
      abdominal computed tomography (CT) scans, 154 cavagrams, 19 lumbar spine
      radiographs, 462 chest radiographs, 108 chest CT scans, and 31 pelvic
      radiographs. The mean imaging follow-up interval was 5.78 months +/- 8.80 (range,
      0.01-56.03 mo). There was no filter fracture or en-bloc migration outside the
      IVC. Upper 95% confidence bounds for the probability of fracture were 1.8% at 6
      months and 4.3% at 12 months. Intracaval filter migration of more than 2 cm
      (mean, 2.43 +/- 0.12 cm; range, -2.54 to 2.99 cm) was seen in 3.9% of patients
      (21 of 534; 12 cranial and nine caudal). CONCLUSIONS: No fracture of a Celect
      filter was observed in this large cohort over a relatively short follow-up
      interval. The results also suggest that the Celect filter has an adequate
      securing mechanism to prevent distant en-bloc or significant intracaval
      migration.

PMID- 24035105
TI  - Ultra-high performance liquid chromatography-atmospheric pressure chemical
      ionization-tandem mass spectrometry for the analysis of benzimidazole compounds
      in milk samples.
AB  - In this work the atmospheric pressure ionization behavior and the tandem mass
      spectrometry fragmentation of 19 benzimidazoles was studied. Several atmospheric
      pressure ionization (API) sources (ESI, APCI and APPI) were evaluated showing
      that APCI was the best option, mainly for KETO-TCB that provided a 20 times
      improvement versus ESI. From the studies of tandem mass spectrometry,
      fragmentation pathways were proposed thus characterizing the most abundant and
      interesting product ions and selecting the most abundant and selective ones for
      the confirmatory quantitative method performed in SRM mode in a triple quadrupole
      mass analyzer. For quantitative analysis, the 19 benzimidazoles were separated in
      less than 7 min using a C18 column packed with superficially porous particles
      providing high efficiency within the range of UHPLC. A QuEChERS-like sample
      treatment was applied to milk samples before the UHPLC-APCI-MS/MS determination
      providing method limits of quantitation that ranged from 0.6 to 3 MUg kg(-1) and
      showing good repeatability (RSD: 2-18%) and accuracy (relative errors: 1-23%)
      suitable for using this method for routine analysis.

PMID- 24035104
TI  - Haemophilus parainfluenzae expresses diverse lipopolysaccharide O-antigens using
      ABC transporter and Wzy polymerase-dependent mechanisms.
AB  - Lipopolysaccharide O-antigens are the basis of serotyping schemes for Gram
      negative bacteria and help to determine the nature of host-bacterial
      interactions. Haemophilus parainfluenzae is a normal commensal of humans but is
      also an occasional pathogen. The prevalence, diversity and biosynthesis of O
      antigens were investigated in this species for the first time. 18/18 commensal H.
      parainfluenzae isolates contain a O-antigen biosynthesis gene cluster flanked by
      glnA and pepB, the same position as the hmg locus for tetrasaccharide
      biosynthesis in Haemophilus influenzae. The O-antigen loci show diverse
      restriction digest patterns but fall into two main groups: (1) those encoding
      enzymes for the synthesis and transfer of FucNAc4N in addition to the Wzy
      dependent mechanism of O-antigen synthesis and transport and (2) those encoding
      galactofuranose synthesis/transfer enzymes and an ABC transporter. The other
      glycosyltransferase genes differ between isolates. Three H. parainfluenzae
      isolates fell outside these groups and are predicted to synthesise O-antigens
      containing ribitol phosphate or deoxytalose. Isolates using the ABC transporter
      system encode a putative O-antigen ligase, required for the synthesis of O
      antigen-containing LPS glycoforms, at a separate genomic location. The presence
      of an O-antigen contributes significantly to H. parainfluenzae resistance to the
      killing effect of human serum in vitro. The discovery of O-antigens in H.
      parainfluenzae is striking, as its close relative H. influenzae lacks this cell
      surface component. 

PMID- 24035106
TI  - Changes in electric activity of masseter and anterior temporalis muscles before
      and after orthognathic surgery in skeletal class III patients.
AB  - OBJECTIVE: The purpose of this study was to evaluate, through clinical and
      electromyographic (EMG) assessments, the electric activity of masseter muscle and
      anterior temporalis muscles during clenching, before and after orthodontic
      treatment and mandibular setback, with or without LeFort I osteotomy, for
      correction of mandibular excess. STUDY DESIGN: Seventeen adult patients (10
      males, 7 females, mean age: 22.5 +/- 2.4 years) were recruited for this study.
      All patients received orthodontic treatment and surgical corrections. EMG
      recordings were obtained from 4 channels of the 8-channel electromyograph FREELY
      (DeGoetzen spa, Olgiate Olona, VA, Italy). RESULTS: A significant difference was
      found in the value of activity index at T0-T1 (33% T0, 1% T1) (P < .05), of
      asymmetry index at T0-T1 (21% T0, 4% T1) (P < .05), and of torque index at T0-T1
      (24% T0, 5% T1) (P < .05). CONCLUSIONS: The evaluation of EMG activity after
      surgery may be considered a sign of good adaptation of the neuromuscular system
      to the new occlusal condition and a good method for detecting nonresponding
      patients who might require further treatment.

PMID- 24035107
TI  - Direct and continuous localization of anatomical landmarks for image-guided
      orthognathic surgery.
AB  - OBJECTIVE: The accuracy and consistency of a new image-guided method for
      orthognathic surgery using direct and continuous landmark localization was
      compared with that of a conventional method. STUDY DESIGN: Maxillary and
      mandibular dental casts mounted on an articulator were used as a surgery phantom.
      We planned six types of surgeries including translations and rotations. The
      sequential positions of the landmarks determined before surgery could be traced
      and the difference between planned and actual positions of the landmarks could be
      visualized during surgery. The final deviation errors were determined with and
      without applying the pointing instrument to the landmarks. RESULTS: The mean RMS
      accuracy of 0.47 +/- 0.22 mm by direct localization was significantly higher than
      that of 1.06 +/- 0.49 mm by the manual localization. There were no significant
      differences in accuracies for surgeries using the direct localization method.
      CONCLUSION: The direct and continuous localization method showed higher accuracy
      and consistency than conventional manual localization in all phantom surgeries.

PMID- 24035108
TI  - Low risk of neurosensory dysfunction after mandibular third molar surgery in
      patients less than 30 years of age. A prospective study following removal of 1220
      mandibular third molars.
AB  - OBJECTIVE: The study aims were to estimate the prevalence of neurosensory
      dysfunction (NSD) and identify risk factors for NSD after mandibular third molar
      (M3) removal. STUDY DESIGN: In this prospective cohort study 864 patients had
      their M3 removed. Age, gender, surgeon's experience, and radiographic findings
      were recorded and the outcome variables were NSD and data analyses. RESULTS: In
      884 patients, 1220 M3 were removed. Fourteen patients reported NSD
      postoperatively; 10 inferior alveolar nerve (IAN) injury, 3 lingual nerve (LN)
      and 1 had injury to both. After 5 years the number of patients with NSD of the
      IAN had decreased to 5, but no change in the LN. CONCLUSION: Age and cortical
      line interruption were significantly associated with the risk of developing
      sensory dysfunction. All patients younger than 30, and 3 of 8 patients older than
      30, had full recovery of the IAN injury. NSD of the LN persisted in all patients.

PMID- 24035109
TI  - CAD presurgical nasoalveolar molding effects on the maxillary morphology in
      infants with UCLP.
AB  - OBJECTIVE: This study evaluated the effectiveness of computer-aided design
      nasoalveolar molding (CAD-NAM) on maxillary alveolar morphology in infants with
      unilateral cleft lip and palate (UCLP). METHODS: 15 infants with UCLP treated by
      CAD-NAM therapy composed the treatment group, and the control group consisted of
      15 infants with non-presurgically treated UCLP. The maxillary morphology was
      analyzed by Rapidform XOR3 software. Differences in all variables pre- and post
      CAD-NAM were discussed. RESULTS: Significant difference was found in arch length,
      cleft gap, labial frenum deviation, A-X, A'-X, and alveolus height on both sides
      pre- and post-CAD-NAM. CONCLUSIONS: This study suggests a trend toward
      morphological improvement in maxillary alveoli of infants with UCLP treated with
      CAD-NAM. The CAD-NAM effectively reduced the cleft gap, corrected the maxilla
      midline, and improved the sagittal length of the maxilla. The alveolar height
      decreased significantly after the treatment, which indicated that the traction
      force of the appliance may have obstructive effects on the vertical growth of the
      alveolar bone.

PMID- 24035110
TI  - Single application of topical doxycycline hyclate in the management of recurrent
      aphthous stomatitis.
AB  - OBJECTIVE: Although tetracyclines are used for topical therapy in recurrent
      aphthous stomatitis (RAS) patients, there are few clinical trials that have used
      doxycycline. Hence, we evaluated the therapeutic efficacy of topical doxycycline
      hyclate in RAS. STUDY DESIGN: A single-blinded placebo-controlled trial
      comprising 50 RAS subjects divided into group A and group B with 25 subjects in
      each group was performed. Patients in group A received topical application of
      crushed doxycycline hyclate tablet with denture adhesive and few drops of saline
      solution once at the initial visit. Group B received placebo similarly. Treatment
      response was assessed by measures of pain reduction, ulcer duration, and adhesive
      retention time. Data were analyzed using the Student t test. RESULTS:
      Participants treated with doxycycline hyclate had significantly less pain by day
      1 (P < .001) and healed faster (P < .001) compared with placebo. CONCLUSION: A
      single application of doxycycline hyclate decreased pain and speeded recovery.

PMID- 24035111
TI  - Serum cyclophilin A concentrations in renal transplant recipients receiving
      cyclosporine A: clinical implications for gingival overgrowth.
AB  - OBJECTIVE: The aim of this study was to investigate the clinical factors in
      relation to the cyclosporine A (CsA) induced gingival overgrowth (GO). STUDY
      DESIGN: Seventy-three participants were assigned as GO+ and GO-. Factors
      including demographic, pharmacological, gingival variables and the serum
      cyclophilin A (CyPA) concentration were analyzed. RESULTS: The occurrence of GO
      was 39.72%. Papillary bleeding index (PBI) had a significantly higher risk of GO
      than plaque index (PI), the ratio of CsA to CyPA, and serum CyPA concentration
      (odds ratio = 364.323, 25.791, 1.002, 0.096, respectively). The severity of GO
      correlated with PI, the ratio of CsA to CyPA, PBI, serum concentrations of CsA
      and CyPA (r = 0.366, 0.355, 0.344, 0.305, and -0.232, respectively). CONCLUSIONS:
      Since a cross-sectional study is not able to explain whether plaque and
      inflammation are the cause or consequence of GO, the ratio of CsA to CyPA may be
      a valuable marker for predicting GO.

PMID- 24035112
TI  - Oral carcinoma cuniculatum: two cases illustrative of a diagnostic challenge.
AB  - Carcinoma cuniculatum is a rare variant of squamous cell carcinoma originally
      described on the sole of the foot and for a long time believed to be restricted
      to the skin. However, since its first description in 1954, several cases have
      been reported at other sites. Carcinoma cuniculatum characteristically invades
      the underlying subcutaneous, submucosal, or bone tissues, forming so-called
      "rabbit burrows," with crypts filled with keratin that are of utmost importance
      for distinguishing this neoplasm from other variants of squamous cell carcinoma.
      Oral carcinoma cuniculatum is an even rarer entity that is frequently
      misdiagnosed initially, a phenomenon described in about one-third of previously
      reported cases. The aim of this report is: (1) to describe the clinicopathologic
      features of 2 new cases of oral carcinoma cuniculatum, initially misdiagnosed as
      infected orthokeratinized cyst and abscess, respectively; and (2) to review the
      related English language literature. 

PMID- 24035113
TI  - Second primary tumors and myeloperoxidase expression in buccal mucosal squamous
      cell carcinoma.
AB  - OBJECTIVE: The present study investigated the relationship between the expression
      of manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase
      (GPx), and myeloperoxidase (MPO) in buccal mucosal squamous cell carcinoma (SCC),
      and the risk of second primary tumors (SPTs). STUDY DESIGN: Immunohistochemistry
      was performed to examine the expression of MnSOD, GPx, catalase, and MPO in
      tissue microarray slides of 173 male patients with buccal mucosal SCC who had
      undergone potentially curative resections. RESULTS: Forty-five (26.01%) patients
      developed SPTs. The prevalent subsites of SPTs were buccal mucosa (48.89%),
      tongue (13.33%), and lip (11.11%). High expression level of MPO was correlated
      with an increased risk of SPTs, even after adjustment for development of
      clinicopathologic parameters (high vs. low expression, adjusted hazard ratio =
      3.89; 95% confidence interval, 1.33-11.41; P = .013). CONCLUSIONS: SPTs are
      common in male buccal mucosal SCC patients. Higher MPO expression in buccal
      mucosal SCC is a risk factor for SPTs.

PMID- 24035114
TI  - Oral HPV infection and persistence in patients with head and neck cancer.
AB  - OBJECTIVE: To investigate the presence and persistence of human papillomavirus
      (HPV) infection in the oral mucosa of patients with head and neck squamous cell
      carcinoma (HNSCC), and its correlation with prognosis. STUDY DESIGN: HPV
      infection was characterized in tumors and pre and posttreatment oral scrapings in
      51 patients with HNSCC and matched controls using the SPF10 LiPA Extra assay.
      p16INK4A immunostain and in situ hybridization for high-risk HPV genotypes
      recognized transcriptionally active infection in tumor samples. The risk of
      infection was compared in patients and controls. The association of pretreatment
      HPV status with recurrence and survival and with posttreatment HPV persistence
      was assessed. RESULTS: Oral HPV infection risk was significantly higher in
      patients with HNSCC than in controls (P < .001). Oral HPV infection was
      associated with infection in the first posttreatment scrapings (P = .015), but
      did not affect recurrence or prognosis. CONCLUSION: Oral HPV infection is
      frequent in patients with HNSCC and has no prognostic implications, suggesting
      that posttreatment polymerase chain reaction monitoring on oral cells is not
      effective to monitor patient recurrence risk.

PMID- 24035115
TI  - Identification of the actinomycete 16S ribosomal RNA gene by polymerase chain
      reaction in oral inflammatory lesions.
AB  - OBJECTIVES: To examine the histopathological characteristics of inflammatory
      lesions containing Actinomyces based on DNA sequencing. Furthermore, case reports
      of actinomycosis in the maxillofacial region are summarized by a review of the
      literature. STUDY DESIGN: The study comprised 12 cases of inflammatory lesions
      containing Actinomyces as diagnosed by DNA analysis. The average age of the
      subjects was 59 +/- 15 years (6 males; 6 females). RESULTS: The distribution of
      causative bacteria was: Actinomyces israelii in 9 cases, Actinomyces gerencseriae
      in 2 cases, and Actinomyces naeslundii in 1 case. Four cases diagnosed by DNA
      sequencing were positive for "Druse," a known morphological diagnostic
      characteristic of actinomycosis, and 8 cases lacked typical colony formation.
      CONCLUSIONS: DNA analysis using paraffin-embedded samples is effective for both
      early and accurate diagnosis of oral lesions containing Actinomyces.

PMID- 24035116
TI  - Potential of fluid-attenuated inversion recovery MRI as an alternative to
      contrast-enhanced MRI for oral and maxillofacial vascular malformations:
      experimental and clinical studies.
AB  - OBJECTIVE: To determine the potential of fluid-attenuated inversion recovery
      (FLAIR) imaging of oral and maxillofacial vascular malformations as an
      alternative to contrast-enhanced magnetic resonance imaging (MRI), we
      investigated the influence of differences in T1 and T2 values on image contrast
      in FLAIR images and evaluated the diagnostic utility of such images. STUDY
      DESIGN: FLAIR imaging and heavily T2-weighted (hT2-weighted) imaging were
      performed using a phantom. FLAIR and hT2-weighted images of 32 lesions (11 mucous
      cysts, 12 vascular malformations, and 9 tumors) were also studied
      retrospectively. The contrast-to-noise ratios (CNRs) and CNR change ratios were
      compared. RESULTS: All aqueous solutions except those with a short T2 value were
      discriminated by CNR change ratio (P < .05). All 3 types of lesions were
      discriminated by CNR change ratio (P < .05). CONCLUSION: FLAIR imaging has
      potential as an alternative to contrast-enhanced MRI in differentiating vascular
      malformations from other types of lesions in the oral and maxillofacial region.

PMID- 24035117
TI  - Correlation between three-dimensional morphological changes of the hyoid bone
      with other skeletal maturation methods in adolescents.
AB  - OBJECTIVE: The study compares growth changes of hyoid bone in cone-beam computed
      tomography (CBCT) with conventional skeletal maturation methods to examine their
      potential implications in the development of a three-dimensional method. STUDY
      DESIGN: Subjects (n = 62, 11-17 years of age) were exposed to CBCT at a six-month
      interval (T1/T2/T3). Ten-hyoid distances were compared with age, hand wrist
      skeletal maturation index (SMI), and cervical vertebral maturation stage (CS).
      RESULTS: The length of greater cornua (GC) was most frequently, moderate to
      highly correlated with age (right: 0.57/0.53/0.58; left: 0.45/0.50/0.48), SMI
      (right: 0.52/0.40/0.45; left: 0.42 at T3), and CS (right: 0.52 at T1), followed
      by the length of the hyoid bone with age (right: 0.50/0.49/0.47; left: 0.44/0.47
      at T1/T2), SMI (right: 0.45/0.41 at T1/T2), and CS (right: 0.48 at T1). The width
      of body of the hyoid (HB) width was correlated with age (0.43/0.44/0.44). The GC
      HB gap was correlated with age (right: -0.41 at T3) and SMI (right: -0.42 at T1).
      CONCLUSION: Peripubertal hyoid maturation did not yield sufficient diagnostic
      information for considerations in the development of a 3D-skeletal maturation
      method.

PMID- 24035118
TI  - Validation of a method for quantifying carotid artery calcification from
      panoramic radiographs.
AB  - OBJECTIVE: Carotid artery calcification can be visualized on panoramic
      radiographs. Incidental observation of these calcifications could identify
      patients in need of further screening. The purpose of this study was to validate
      the assessment and quantification of calcification on panoramic radiographs with
      the stenosis and the calculated resistive index (RI) from Doppler
      ultrasonography. STUDY DESIGN: Digital panoramic radiographs were used to assess
      the area of carotid artery calcification using tools available in NIH's ImageJ.
      Inpatient and outpatient discharge records were reviewed to identify subjects
      with a completed carotid Doppler ultrasound exam (n = 122). RESULTS: The
      quantification of carotid artery calcification was found to correlate well with
      the degree of stenosis (area under the curve [AUC] 0.81 [95% confidence interval
      [CI] 0.64, 0.98]) and the RI of the common carotid artery (AUC 0.79 [95% CI 0.59,
      0.98]). CONCLUSION: This method for quantification of carotid artery
      calcification could identify patients in need of further evaluation.

PMID- 24035119
TI  - A rare clinical presentation of sarcoidosis; gingivitis.
AB  - Gingivitis due to sarcoidosis is a relatively rare condition. Gingivitis or
      isolated gingival involvement may be the first sign of systemic sarcoidosis. We
      report the case of a 37 year-old woman with isolated gingivitis due to
      sarcoidosis confirmed by biopsy. Following treatment with a systemic
      corticosteroid (prednisolone 40 mg/day), all clinical and radiologic findings
      were completely improved. In cases of chronic and intractable gingivitis,
      systemic sarcoidosis should be suspected. It should be confirmed with a biopsy,
      and the patient should be referred to a chest disease clinic to exclude other
      organ involvement. 

PMID- 24035120
TI  - Hypoplasia of the parotid gland: computed tomography sialography diagnosis.
AB  - We report two unusual cases of non-syndromic hypoplasia of the parotid gland. The
      hypoplastic parotid gland mimicked a preauricular parotid tumor in one case and
      presented as an incidental image finding in the other case. Absence of the deep
      lobe and isthmus of the parotid parenchyma could be determined on axial computed
      tomography (CT) by revealing fat tissue composition of the parotid space. The
      underdeveloped superficial lobe of the gland was observed on three-dimensional CT
      sialography. 

PMID- 24035121
TI  - Radiologists' burden of inefficiency using conventional imaging workstations.

PMID- 24035122
TI  - Optimizing radiation use during fluoroscopic procedures: a quality and safety
      improvement project.
AB  - PURPOSE: The ionizing radiation used during fluoroscopically guided medical
      interventions carries risk. The teams performing these procedures seek to
      minimize those risks while preserving each procedure's benefits. This report
      describes a data-driven optimization strategy. METHODS: Manual and automated data
      capture systems were used to collect a series of different metrics, including
      fluoroscopy time, kerma area product, and reference point air kerma, from both
      adult and pediatric interventional radiologic procedures. Tools from statistical
      process control were used to identify opportunities for improvement and assess
      which changes led to improvement. RESULTS: Initial efforts focused on creating a
      system capable of reliably capturing fluoroscopy time from all interventional
      radiologic procedures. Ongoing data analysis and feedback to frontline teams led
      to the development of a manual workflow that reliably captured fluoroscopy time.
      Data capture was later supplemented by automatic capture of electronic records.
      This process exploited the standardized format (DICOM Structured Reporting) that
      newer fluoroscopy units use to record the radiation metrics. Data analysis found
      marked differences between the imaging protocols used for adults and children.
      Revision of the adult protocols led to a stable twofold reduction in average
      exposure per adult procedure. Analysis of balancing measures found no impact on
      workflow. CONCLUSIONS: A systematic approach to improving radiation use during
      procedures led to a substantial and sustained reduction in risk with no reduction
      in benefits. Data were readily captured by both manual and automated processes.
      Concepts from cognitive psychology and information theory provided a theoretical
      basis for both data analysis and improvement opportunities.

PMID- 24035123
TI  - Screening cervical spine CT in the emergency department, phase 3: increasing
      effectiveness of imaging.
AB  - PURPOSE: The aim of this study was to determine the effect of a clinical
      education initiative on the appropriate utilization of screening cervical spine
      CT in the emergency department. The purpose was to assess if clinical education
      can produce stricter adherence to the ACR Appropriateness Criteria and improve
      the utilization of screening CT examinations in the emergency department.
      METHODS: Institutional review board approval was obtained for this HIPAA
      compliant study. All adult patients presenting to a level 1 trauma center with
      blunt trauma prompting screening cervical spine CT were eligible. For each study,
      the requesting clinician completed a survey selecting all clinical indications.
      CT examinations were evaluated by a board-certified radiologist blinded to survey
      data. Results were compared with retrospective and prospective studies performed
      before the institution of the education initiative. RESULTS: Of the 388 cervical
      spine CT examinations performed, 12 (3.1%) were positive for acute cervical spine
      injury, compared to only 1.0% before the clinical education program (phase 2). Of
      the 376 examinations without injury, 13% met all 5 National Emergency X
      Radiography Utilization Study criteria for nonimaging (down from 16.1% in phase
      2), and 15 (4%) required no imaging when both National Emergency X-Radiography
      Utilization Study and abbreviated Canadian cervical spine rule criteria were
      applied. CONCLUSIONS: Implementation of a clinical education initiative resulted
      in improved adherence to ACR Appropriateness Criteria and improved clinical
      effectiveness of the studies by increasing fracture detection rate. Initiatives
      such as these could potentially influence imaging overutilization without
      burdening emergency department clinicians with excessive roadblocks to image
      ordering.

PMID- 24035124
TI  - The autopsy of chicken nuggets reads "chicken little".
AB  - PURPOSE: To determine the contents of chicken nuggets from 2 national food
      chains. BACKGROUND: Chicken nuggets have become a major component of the American
      diet. We sought to determine the current composition of this highly processed
      food. METHODS: Randomly selected nuggets from 2 different national fast food
      chains were fixed in formalin, sectioned and stained for microscopic analysis.
      RESULTS: Striated muscle (chicken meat) was not the predominate component in
      either nugget. Fat was present in equal or greater quantities along with
      epithelium, bone, nerve, and connective tissue. CONCLUSION: Chicken nuggets are
      mostly fat, and their name is a misnomer.

PMID- 24035125
TI  - Lower A1c targets in type 2 diabetes and increased mortality: causal or casual?

PMID- 24035126
TI  - Wetting-dewetting films: the role of structural forces.
AB  - The liquid wetting and dewetting of solids are ubiquitous phenomena that occur in
      everyday life. Understanding the nature of these phenomena is beneficial for
      research and technological applications. However, despite their importance, the
      phenomena are still not well understood because of the nature of the substrate's
      surface energy non-ideality and dynamics. This paper illustrates the mechanisms
      and applications of liquid wetting and dewetting on hydrophilic and hydrophobic
      substrates. We discuss the classical understanding and application of wetting and
      film stability criteria based on the Frumkin-Derjaguin disjoining pressure model.
      The roles of the film critical thickness and capillary pressure on the film
      instability based on the disjoining pressure isotherm are elucidated, as are the
      criteria for stable and unstable wet films. We consider the film area in the
      model for the film stability and the applicable experiments. This paper also
      addresses the two classic film instability mechanisms for suspended liquid films
      based on the conditions of the free energy criteria originally proposed by de
      Vries (nucleation hole formation) and Vrij-Scheludko (capillary waves vs. van der
      Waals forces) that were later adapted to explain dewetting. We include a
      discussion of the mechanisms of nanofilm wetting and dewetting on a solid
      substrate based on nanoparticles' tendency to form a 2D layer and 2D inlayer in
      the film under the wetting film's surface confinement. We also present our view
      on the future of wetting-dewetting modeling and its applications in developing
      emerging technologies. We believe the review and analysis presented here will
      benefit the current and future understanding of the wetting-dewetting phenomena,
      as well as aid in the development of novel products and technologies. 

PMID- 24035127
TI  - Incidence and grading of cranio-facial osteosarcomas.
AB  - Osteosarcoma of the cranio-facial structures and skull is rare. In children, only
      5.6% of cases are localized in these areas. It is claimed that the mean age at
      presentation is at least 10-15 years higher than for osteosarcomas in other parts
      of the body. However these reports are based on data from single institutions or
      compiled from several registries. It is further claimed that tumours in the
      mandible and maxilla are less malignant, as based on observations of a better
      prognosis and lower incidence of metastatic spread as compared with osteosarcomas
      arising elsewhere. We report all histologically proven cranio-facial
      osteosarcomas in The Netherlands occurring over a 20-year period, based on the
      national registration covering all Dutch pathology laboratories (PALGA). The age
      corrected incidence of primary osteosarcoma ranged from 0.33 to 0.41 per million
      across the age ranges. The mandible was the most frequent site of involvement.
      Only 61% had a high malignant histological grading. Our data indicate that the
      age-corrected incidence of primary osteosarcomas is similar across all age
      ranges. In respect to histology, a lower grade of malignancy is more frequent.
      Maxillary lesions significantly more often have a lower histological grade of
      malignancy. 

PMID- 24035128
TI  - Pedicle length in the inferiorly based buccinator myomucosal island flap: a
      cadaveric study.
AB  - The inferiorly based buccinator myomucosal island flap is a useful reconstructive
      option for medium-sized intraoral mucosal defects. The pedicle length of this
      flap has not yet been determined. Thirteen fresh cadavers (26 sides) with intact
      faces were studied. An inferiorly based buccinator myomucosal island flap was
      elevated. Various measurements were taken, including pedicle length, paddle area,
      and pedicle length after dissection of the facial artery through the
      submandibular salivary gland; the presence of the facial artery or vein in the
      pedicle and the number of perforators were also evaluated. The mean pedicle
      lengths in the right and left sides were 4.8+/-0.6cm and 4.9+/-0.6cm,
      respectively. The mean pedicle lengths after dissection of the facial artery
      through the submandibular salivary gland were 7.8+/-0.7cm (right side) and 7.7+/
      0.6cm (left side). The pedicle contained only the facial artery in six sides.
      There were two to three perforator branches from the facial artery to the mucosal
      paddle. Paddle sizes of the flap were in the range of 2.2*2.1cm to 3.5*3cm. This
      flap is suitable for the reconstruction of the floor of the mouth and tongue.
      Pedicle length can be increased significantly by dissecting the facial artery
      through the submandibular salivary gland. 

PMID- 24035129
TI  - Rehabilitation of medically complex ectodermal dysplasia with novel surgical and
      prosthodontic protocols.
AB  - The functional and aesthetic needs of a 17-year-old patient afflicted with
      ectodermal dysplasia, chronic long-term immunosuppression, cleft palate,
      velopharyngeal insufficiency, hypernasality, maxillary hypoplasia, and
      oligodontia were met with a multidisciplinary team approach. Predictable
      functional and aesthetic outcomes were obtained with a combination of injection
      augmentation of the soft palate and nasopharynx and rigid fixation maxillary
      external distraction with immediate placement and immediate load protocols. No
      biological or prosthetic complications were noted after definitive rehabilitation
      with a mandibular implant-retained fixed prosthesis and a maxillary implant
      retained detachable prosthesis. 

PMID- 24035130
TI  - Clinical commentary in response to "The effect of finger joint mobility on
      precision grip force".

PMID- 24035131
TI  - Does "it get better" for depressed sexual minority youth in young adulthood?
AB  - PURPOSE: To examine depressive symptoms and suicidality in adolescence and
      adulthood in a sample of depressed adolescents in five sexual identity groups
      (heterosexual, mostly heterosexual, bisexual, mostly gay, and gay). METHODS:
      Depressed adolescents (N = 1,591) from the National Longitudinal Study of
      Adolescent Health were examined again in young adulthood. RESULTS: Paired t-tests
      revealed that depressive symptoms declined significantly in all five sexual
      identity groups. McNemar chi-square tests revealed that the percentage of
      participants reporting suicidal ideation decreased significantly in all groups
      except for the mostly gay group. The percentage of participants reporting suicide
      attempts declined in all groups except the bisexual group. CONCLUSIONS: Within
      group differences are important to consider in delivering effective mental health
      services. Although depressive symptoms diminished in young adulthood in all
      groups, suicidality did not. Mostly gay and bisexual young adults did not report
      the same significant declines as their peers.

PMID- 24035132
TI  - A multicenter, open-label, observational study of testosterone gel (1%) in the
      treatment of adolescent boys with klinefelter syndrome or anorchia.
AB  - PURPOSE: To assess the safety and clinical outcomes of 6-month treatment with
      testosterone gel 1% therapy in adolescent boys with primary hypogonadism
      resulting from Klinefelter syndrome (KS) or anorchia. METHODS: This was a
      subgroup analysis of a multicenter, open-label study of adolescent boys (N = 86)
      with delayed puberty who received .5-5.0 g testosterone gel 1% daily for <=6
      months. Adolescent boys 12-17 years of age with KS (n = 21) or anorchia (n = 8),
      bone age >=10.5 years, and baseline growth data >=6 months were included in this
      analysis. Serum hormone levels (total/free testosterone, luteinizing hormone,
      dihydrotestosterone, follicle-stimulating hormone, and estradiol) were measured
      using validated assays. Safety was assessed through adverse events (AEs).
      RESULTS: At baseline, patients with KS were taller, weighed more, and had higher
      total testosterone levels (mean 174 vs. 19 ng/dL) than patients with anorchia. At
      6 months, total and free testosterone and dihydrotestosterone levels increased
      1.8- to 2.3-fold in the KS group and eight- to 10-fold in anorchia patients.
      Estradiol levels increased 1.9-fold in the anorchia group and 1.4-fold in the KS
      group after treatment. No clinically significant changes were noted for
      luteinizing hormone, follicle-stimulating hormone, and sex hormone-binding
      globulin concentrations in either group. Cough was the most common AE (eight of
      29), followed by acne and headache (both four of 29). One anorchia and two KS
      patients discontinued prematurely. CONCLUSIONS: Once-daily testosterone gel
      application increased serum testosterone levels into the pubertal range and
      maintained pubertal testosterone levels during 6-month treatment. In this study,
      testosterone gel 1% raised testosterone levels and was associated with cough as
      the most common AE.

PMID- 24035133
TI  - Maternal underestimation of child's sexual experience: suggested implications for
      HPV vaccine uptake at recommended ages.
AB  - PURPOSE: Despite official recommendation for routine HPV vaccination of boys and
      girls at age 11-12 years, parents and providers are more likely to vaccinate
      their children/patients at older ages. Preferences for vaccinating older
      adolescents may be related to beliefs about an adolescent's sexual experience or
      perceived parental resistance to vaccinating children who are assumed to be
      sexually inexperienced. METHODS: Using data from the 1995 wave of the National
      Longitudinal Study of Adolescent Health (ADD Health), a subset of a nationally
      representative sample of adolescents in grades 7 through 12 and their parents (n
      = 13,461), we investigated maternal underestimation of adolescent sexual
      experience. RESULTS: About one third (34.8%) of adolescents reported being
      sexually experienced and of these, 46.8% of their mothers inaccurately reported
      that their child was not sexually experienced. Underestimation varied by
      adolescent age with 78.1% of mothers of sexually active 11-13-year-olds reporting
      their child was not sexually active, compared with 56.4% of mothers of sexually
      active 14-16-year-olds and only 34.4% of mothers of 17-18-year-olds. CONCLUSIONS:
      Although most adolescents are not sexually active at age 11 or 12 years, waiting
      until a parent thinks a child is sexually active could result in missed
      opportunities for prevention.

PMID- 24035134
TI  - Activation of mammalian target of rapamycin signaling pathway markers in minute
      adenocarcinoma of the prostate.
AB  - OBJECTIVE: To asses the mammalian target of rapamycin (mTOR) pathway in minute
      prostatic adenocarcinoma on the basis of the previously reported role of
      phosphatase and tensin homolog (PTEN) inactivation and mTOR pathway activation as
      a negative prognosticator in prostatic cancer. METHODS: Tissue microarrays were
      constructed from 42 consecutive radical prostatectomy specimens with minute
      prostatic adenocarcinoma. Standard immunohistochemistry analysis for mTOR pathway
      members PTEN, phos-S6, phos-4E-BP1, phos-mTOR, phos-AKT, p27, and ERG was
      performed. For all markers, histologic expression score was calculated as the sum
      of intensity * extent of expression. In addition, for PTEN, presence of "markedly
      decreased" expression (any focal absence of expression) was also assessed.
      Expression status of all biomarkers was compared between tumor and paired benign
      tissue. Intercorrelation among markers was also performed. RESULTS: PTEN
      expression was seen in all 36 evaluable minute prostatic adenocarcinoma.
      Cytoplasmic phos-S6 was present in 32 of 36 tumors (89%). phos-S6 expression
      levels were higher in tumors compared with paired benign tissue (P = .007).
      Cytoplasmic and nuclear phos-4E-BP1 was present in all 34 evaluable tumors. phos
      4E-BP1 was significantly higher in cancer compared with normal tissue (P <.0001).
      Only a minority of tumors demonstrating higher phos-S6 expression and phos-4E-BP1
      (2 of 32 and 2 of 34, respectively) had associated "markedly decreased" PTEN
      expression. CONCLUSION: We found evidence of activation of mTOR pathway in minute
      prostatic adenocarcinoma that appears to be unrelated to "markedly decreased"
      PTEN expression. The latter finding suggests an alternative signaling mechanism
      controlling mTOR activation in minute prostate carcinoma.

PMID- 24035137
TI  - A national-scale picture of U.S. cattle movements obtained from Interstate
      Certificate of Veterinary Inspection data.
AB  - We present the first comprehensive description of how shipments of cattle connect
      the geographic extent and production diversity of the United States cattle
      industry. We built a network of cattle movement from a state-stratified 10%
      systematic sample of calendar year 2009 Interstate Certificates of Veterinary
      Inspection (ICVI) data. ICVIs are required to certify the apparent health of
      cattle moving across state borders and allow us to examine cattle movements at
      the county scale. The majority of the ICVI sample consisted of small shipments
      (<20 head) moved for feeding and beef production. Geographically, the central
      plains states had the most connections, correlated to feeding infrastructure. The
      entire nation was closely connected when interstate movements were summarized at
      the state level. At the county-level, the U.S. is still well connected
      geographically, but significant heterogeneities in the location and identity of
      counties central to the network emerge. Overall, the network of interstate
      movements is described by a hub structure, with a few counties sending or
      receiving extremely large numbers of shipments and many counties sending and
      receiving few shipments. The county-level network also has a very low proportion
      of reciprocal movements, indicating that high-order network properties may be
      better at describing a county's importance than simple summaries of the number of
      shipments or animals sent and received. We suggest that summarizing cattle
      movements at the state level homogenizes the network and a county level approach
      is most appropriate for examining processes influenced by cattle shipments, such
      as economic analyses and disease outbreaks. 

PMID- 24035138
TI  - Distal interphalangeal joint arthrodesis.

PMID- 24035135
TI  - Cytoplasmic dynein heavy chain: the servant of many masters.
AB  - Cytoplasmic dynein is the main retrograde motor in all eukaryotic cells. This
      complex comprises different subunits assembled on a cytoplasmic dynein heavy
      chain 1 (DYNC1H1) dimer. Cytoplasmic dynein is particularly important for neurons
      because it carries essential signals and organelles from distal sites to the cell
      body. In the past decade, several mouse models have helped to dissect the
      numerous functions of DYNC1H1. Additionally, several DYNC1H1 mutations have
      recently been found in human patients that give rise to a broad spectrum of
      developmental and midlife-onset disorders. Here, we discuss the effects of
      mutations of mouse and human DYNC1H1 and how these studies are giving us new
      insight into the many critical roles DYNC1H1 plays in the nervous system. 

PMID- 24035140
TI  - Ultrasonic enhancing amorphization during synthesis of calcium phosphate.
AB  - Amorphous calcium phosphate (ACP) has great application potential in biomaterials
      field due to its non-cytotoxicity, high bioactivity, good cytocompatibility, and
      so on. The results of this research demonstrated that ultrasonic obviously
      enhanced amorphization during synthesis of calcium phosphate. The ACP phase was
      relatively ideal when the solvent of Ca(NO3)2.4H2O was ethanol and the solvent of
      (NH4)2HPO4 was a mixture of water and ethanol, under ultrasonic. In-situ
      crystallization of ACP could be observed by HRTEM. The mechanism on the effects
      of ultrasonic on amorphization of the synthesized calcium phosphate was
      discussed. It was suggested that ultrasonic synthesis might be a facile method to
      prepare pure and safe ACP related biomaterials. 

PMID- 24035139
TI  - Th17-mediated inflammation in asthma.
AB  - Asthma is a heterogeneous disease with many different phenotypes. Moderate and
      severe asthma phenotypes have been associated with increased neutrophils and
      increased Th17 cytokines, IL-17A, IL-17F, and IL-22, in the bronchoalveolar
      lavage fluid of patients. Th17 cytokines recruit neutrophils to the airway by
      increasing secretion of epithelial-derived neutrophilic chemokines. In addition,
      Th17 cytokines also induce mucous cell metaplasia and have pleotropic effects on
      airway smooth muscle resulting in airway narrowing. The role of Th17 cytokines in
      regulating Th2 cytokine expression and allergic airway inflammation remains
      unclear with conflicting reports. However, the role of Th17 cells in asthma will
      be answered in ongoing clinical trials with therapeutics targeting IL-17A and IL
      17 receptor signaling. 

PMID- 24035141
TI  - Systematic error of cardiac output measured by bolus thermodilution with a
      pulmonary artery catheter compared with that measured by an aortic flow probe in
      a pig model.
AB  - OBJECTIVE: The precision of thermodilution cardiac output measurement using a
      pulmonary artery catheter can be divided into random and systematic errors. This
      study determined the systematic component. DESIGN: Comparative validation against
      a transonic flow probe on the aortic root. SETTING: Animal research laboratory.
      PARTICIPANTS: Eight anesthetized pigs, weight 27 to 32 kg. INTERVENTIONS:
      Thermodilution measurements were compared to those from an aortic flow probe. One
      (or two) catheters were tested in each pig, with multiple paired readings
      recorded as cardiac output was varied pharmacologically by esmolol, epinephrine,
      or dopamine. Linear regression lines were drawn for each pig as well as the slope
      used to quantify systematic error. Regression analysis of data from each pig was
      used to assess trending. Bland-Altman analysis also was performed. MEASUREMENTS
      AND MAIN RESULTS: Systematic error derived from slope data was +/- 26%. Trending
      was reliable in 8 out of 10 catheter placements (p value>0.95). Bland- Altman
      analysis (n = 77 basal anesthesia and 165 pharmacologic intervention data pairs)
      provided percentage errors of +/- 23% and +/- 34-39%, respectively. This
      percentage error increase was due to variations in calibration and the slopes of
      regression lines for each catheter tested as the lines diverged as cardiac output
      increased, widening the spread of data. CONCLUSIONS: Thermodilution does trend
      cardiac output reliably in most cases. However, the systematic error is large and
      has a significant effect on the percentage error as cardiac output increases. The
      precision error of +/- 20% currently used for thermodilution measurement may be
      set too low and is dependent on the clinical setting.

PMID- 24035142
TI  - Computer-enhanced interventions for drug use and HIV risk in the emergency room:
      preliminary results on psychological precursors of behavior change.
AB  - This article describes process data from a randomized controlled trial among 781
      adults recruited in the emergency department who reported recent drug use and
      were randomized to: intervener-delivered brief intervention (IBI) assisted by
      computer, computerized BI (CBI), or enhanced usual care (EUC). Analyses examined
      differences between baseline and post-intervention on psychological constructs
      theoretically related to changes in drug use and HIV risk: importance, readiness,
      intention, help-seeking, and confidence. Compared to EUC, participants receiving
      the IBI significantly increased in confidence and intentions; CBI patients
      increased importance, readiness, confidence, and help-seeking. Both groups
      increased relative to the EUC in likelihood of condom use with regular partners.
      Examining BI components suggested that benefits of change and tools for change
      were associated with changes in psychological constructs. Delivering BIs
      targeting drug use and HIV risk using computers appears promising for
      implementation in healthcare settings. This trial is ongoing and future work will
      report behavioral outcomes. 

PMID- 24035143
TI  - Predictive modeling of addiction lapses in a mobile health application.
AB  - The chronically relapsing nature of alcoholism leads to substantial personal,
      family, and societal costs. Addiction-comprehensive health enhancement support
      system (A-CHESS) is a smartphone application that aims to reduce relapse. To
      offer targeted support to patients who are at risk of lapses within the coming
      week, a Bayesian network model to predict such events was constructed using
      responses on 2,934 weekly surveys (called the Weekly Check-in) from 152 alcohol
      dependent individuals who recently completed residential treatment. The Weekly
      Check-in is a self-monitoring service, provided in A-CHESS, to track patients'
      recovery progress. The model showed good predictability, with the area under
      receiver operating characteristic curve of 0.829 in the 10-fold cross-validation
      and 0.912 in the external validation. The sensitivity/specificity table assists
      the tradeoff decisions necessary to apply the model in practice. This study moves
      us closer to the goal of providing lapse prediction so that patients might
      receive more targeted and timely support. 

PMID- 24035144
TI  - Cobalt chains composed of hexagonal intercrossed microplatelets: shape-controlled
      synthesis, growth mechanism, and magnetic properties.
AB  - Self-assembled Co chains made up of hexagonal intercrossed microplatelets have
      been fabricated via a facile solvothermal approach in a mixed solution of
      ethylene glycol (EG) and ethylenediamine (EDA) with poly(vinylpyrrolidone) (PVP)
      and dodecanethiol (DDT) as surfactants. The morphology and size of the products
      can be easily controlled through properly monitoring the synthetic conditions,
      such as the volume ratio of EG/EDA, reaction temperature, reaction time,
      concentrations of NaOH, and the amount of both PVP and dodecanethiol. Based on a
      series of contrast experiments, a stepwise growth mechanism of Co chains was
      rationally conjectured. During the shape evolution process, layered beta-Co(OH)2
      platelets were first formed and then reduced to Co platelets, which finally
      developed to one-dimensional Co chains composed of hexagonal close-packed
      microplatelets. It is noteworthy that hexagonal Co microplatelets were inherited
      from their layered precursor Co(OH)2 microplatelets obtained in the initial
      stage. Compared to bulk cobalt, the as-obtained platelet-like Co microchains
      manifested an enhanced coercivity (Hc) and a decreased saturation magnetization
      (Ms), which could be ascribed to the highly anisotropic shape of platelet-like
      subunits. Such platelet-like 1D cobalt microchains are expected to afford new
      opportunities for applications in the field of magnetic storage and catalysis. 

PMID- 24035145
TI  - Designing and implementing reflective practice programs--key principles and
      considerations.
AB  - This paper reports on an educational evaluation study that sought to identify key
      principles that could inform the design and implementation of undergraduate
      nursing reflection programs and thereby enhance the potential that nursing
      students will develop sound reflective practice. Semi-structured interviews were
      conducted with nursing graduates to explore their perceptions of an undergraduate
      Bachelor of Nursing reflection subject and explicate the factors that could
      enhance the implementation of this subject. Subsequent validation and refinement
      of these factors was managed by correlating the factors with students'
      qualitative feedback, gathered through a formal subject evaluation of the
      undergraduate reflective practice subject. The correlation analysis, ascertained
      three principles that are posited as highly significant in the design and
      implementation of undergraduate reflective practice nursing programs. These
      principles, which are explained in this paper, despite being conceptualised in an
      Australian University have relevance and are appropriate across national and
      discipline boundaries and could be used in the design and implementation of any
      reflection subject, particularly those in undergraduate programs.

PMID- 24035146
TI  - Low testosterone and the risk of dementia in elderly men: Impact of age and
      education.
AB  - OBJECTIVE: The objective of this study was to examine the association of plasma
      estradiol and testosterone with risk for dementia in elderly men. METHODS: Within
      the population based Three-City study, including 3650 men age 65 years and older,
      a case-cohort design was set up after 4-years of follow-up. Baseline plasma
      levels of total 17-beta estradiol (Total-E2), total testosterone (total-T) and
      bioavailable testosterone (bio-T) were measured for all cases of incident
      dementia (n=105) and for a random sample of the cohort (n=413). Cox regression
      models were used to estimate multivariate steroid sex hormone-associated hazard
      ratios (HR) and 95% confidence intervals of dementia. RESULTS: There was a
      reverse J-shaped relationship between total-T and risk for dementia (P=.007).
      Compared with the median tertile, the HRs associated with total-T in the lower
      and upper tertile were increased (HR, 2.33; P=.026; HR, 1.9, P=.126;
      respectively). Low bio-T was associated with a greater risk for dementia (HR for
      one standard deviation of decreasing log(bio-T), 1.29; 95% confidence interval,
      1.03-1.62). An interaction was found between bio-T and age (P<.0001), and bio-T
      and education (P=.044). Risk for dementia associated with low bio-T was greater
      in older men (80 years or older) than in younger men (younger than 80 years; HR,
      3.11; P=.011 vs. HR, 1.07, P=.715, respectively) and in men with high level of
      education compared with those with low level of education (HR, 2.32; P=.0002 vs.
      HR, 0.95; P=.790, respectively). No significant association was found between
      Total-E2 and dementia. CONCLUSIONS: Low levels of testosterone are associated
      with a risk for dementia in elderly men. The association between low bio-T and
      dementia may be more relevant to men 80 years or older and men with a high level
      of education.

PMID- 24035147
TI  - Midlife risk score for the prediction of dementia four decades later.
AB  - OBJECTIVE: The objective of this study was to obtain external validation of the
      only available midlife dementia risk score cardiovascular risk factors , aging
      and dementia study (CAIDE) constituting age, education, hypertension, obesity,
      and hyperlipidemia in a larger, more diverse population. Our second aim was to
      improve the CAIDE risk score by additional midlife risk factors. METHODS: This
      retrospective cohort study was conducted in an integrated health care delivery
      system. A total of 9480 Kaiser Permanente members who participated in a health
      survey study (age range, 40-55 years) from 1964 to 1973 were included in this
      study. Dementia diagnoses from primary care and medical specialist visits were
      collected from January 1, 1994 to January 16, 2006, using International
      Classification of Diseases 9 codes 290.0, 290.1 for "possible dementia," and
      331.0 and 290.4 for "specialist confirmed dementia." Risk model prediction and
      validation were examined with the C statistic, net reclassification improvement,
      and integrated discrimination improvement. Dementia risk per sum score was
      calculated with Kaplan-Meier estimates. RESULTS: A total of 2767 participants
      (25%) were diagnosed with any type of dementia, of which 1011 diagnoses (10.7%)
      were specialist-confirmed diagnoses. Average time between midlife examination and
      end of follow-up was 36.1 years. The CAIDE risk score replicated well with a C
      statistic of 0.75, quite similar to the original CAIDE C statistic of 0.78. The
      CAIDE score also predicted well within different race strata. Other midlife risk
      factors (central obesity, depressed mood, diabetes mellitus, head trauma, lung
      function, and smoking) did not improve predictability. The risk score allowed
      stratification of participants into those with 40-year low (9%) and high (29%)
      dementia risk. CONCLUSIONS: A combination of modifiable vascular risk factors in
      midlife is highly predictive of the likelihood of dementia decades later.
      Possible dementia prevention strategies should point to a life course perspective
      on maintaining vascular health.

PMID- 24035149
TI  - Unlocking the resistance to wheat lipid transfer protein.

PMID- 24035148
TI  - Design of a comprehensive Alzheimer's disease clinic and research center in Spain
      to meet critical patient and family needs.
AB  - OBJECTIVES: Alzheimer's disease (AD) affects people worldwide, and the prevalence
      is increasing as the population ages. There is an international effort to
      understand the biology of AD to develop primary and secondary prevention
      strategies, and to develop effective therapeutic interventions for individuals
      who are already symptomatic. One of the critically important pieces of all
      national plans to address AD is the call for the development of service models to
      deliver quality, effective care based on the best evidence available. METHODS: We
      describe one type of care model developed by the Fundacio ACE, Institut Catala de
      Neurociencies Aplicades (Fundacio ACE, Barcelona, Spain) that integrates
      diagnosis, therapy, follow-up care, daycare, and a day hospital, and does so in
      the context of an active clinical research and educational program. RESULTS:
      There were 13,048 individuals newly evaluated and diagnosed in Fundacio ACE
      between 1996 and 2011. Of these, 6132 had AD (47.0%), 3871 had mild cognitive
      impairment (MCI) (29.7%), and 1958 had no cognitive impairment (15.0%). Follow-up
      information is available on 4735 (47.3%) AD and MCI patients, and these data
      indicate that MCI develops into dementia at a rate of 222.6/1000 person-years.
      Apolipoprotein E (APOE) genotyping was available in 22.4% of the patients. The
      epsilon4 allele occurred in 45.7% of the AD patients, in 37.8% of the MCI
      subjects, and in 31.6% of those without cognitive impairment. CONCLUSIONS:
      Fundacio ACE can serve as a model system that can be adapted to other settings
      within their specific cultural, governmental, and legal constraints.

PMID- 24035150
TI  - Sphingomyelin and ceramide are physiological ligands for human LMIR3/CD300f,
      inhibiting FcepsilonRI-mediated mast cell activation.

PMID- 24035151
TI  - Is intralymphatic immunotherapy ready for clinical use in patients with grass
      pollen allergy?

PMID- 24035152
TI  - Reply: To PMID 24035149.

PMID- 24035153
TI  - Acellular adipose matrix as a natural scaffold for tissue engineering.
AB  - BACKGROUND: In conventional tissue-regeneration technologies, stem cells and/or
      other cells are injected into or incubated on scaffolds. In general, scaffolds
      can be classified into synthetic and natural polymers and natural matrices.
      Polymers are generally less suitable than natural matrices in terms of
      biocompatibility and biodegradability. A highly promising alternative may be the
      acellular adipose matrix (AAM), which is a natural scaffold that could mediate
      tissue regeneration without any artefacts. The optimal method for adipose-tissue
      decellularisation is described in this article. METHODS: Discarded human adipose
      tissues harvested from routine operations were used. In experiment 1, four
      different adipose-tissue-decellularisation methods were compared and modified. In
      experiment 2, the most effective method was tested by using adipose-tissue blocks
      from various donor sites (the abdomen, chest and forearm) and of different
      weights (0.8, 25 and 80 g). Haematoxylin and eosin (H &E) staining,
      immunohistochemistry (IHC) and scanning electron microscopy were used to
      determine the efficacy of decellularisation. RESULTS: In experiment 1, a method
      using an enzymatic digestion solution yielded complete decellularisation after
      some modifications. In experiment 2, the 0.8-g specimens were completely
      decellularised by the modified method. However, cell components remained in the
      25- and 80-g specimens. The donor site had no effect on the degree of
      decellularisation. CONCLUSIONS: An optimal method for adipose-tissue
      decellularisation is reported. Because AAM is a natural collagen scaffold that is
      of human origin, this report describes an important first step in a tissue
      engineering innovation that may be suitable for the regeneration of various
      tissues.

PMID- 24035154
TI  - Renal cell carcinoma metastasis to a contralateral oncocytoma in a patient
      presenting with bilateral synchronous renal tumors.

PMID- 24035155
TI  - Polymorphisms of the bone morphogenetic protein 7 gene (BMP7) and association
      analysis with sow productive traits.
AB  - Bone morphological protein 7 (BMP7) has been proposed to be an osteoinductive
      protein. Recent data have shown that BMP7 also plays a crucial role in the growth
      and development, and physiological function of reproductive system. To date,
      studies have shown an association between the BMP gene family and reproduction in
      many populations, but few studies have completely described this association in
      sow. In the present study, three sow breeds were screened out to investigate the
      genetic effects of the BMP7 gene. Using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) and DNA sequencing, three single
      nucleotide polymorphisms (SNPs) (g.35161T>C, g.35175T>C and g.35216C>T) were
      identified in intron 2 of the BMP7 gene. Associations between the three SNPs and
      the number of piglet born alive (NBA), litter weight at birth (LBW), total number
      of piglet born (TNB) and litter weight at 21 days were analyzed using association
      analysis. Among the three SNPs, g.35161T>C was significantly associated with NBA
      and LBW (p<0.05), and the litter weight at 21 days (p<0.01). These results
      suggest that g.35161T>C is a potential candidate gene locus for litter size
      traits and the BMP7 gene might be associated with the quantitative trait locus
      (QTL) controlling the litter size. These data will provide a background for more
      extensive characterization of the BMP7 gene.

PMID- 24035156
TI  - Characterization of prostaglandin E2 receptors (EP2, EP4) in the horse oviduct.
AB  - Biological effects of prostaglandin E2 are mediated via one of four receptors
      designated EP1, EP2, EP3 and EP4 which are encoded by separate genes. In general,
      EP1 and EP3 induce smooth muscle contraction whereas EP2 and EP4 induce smooth
      muscle relaxation. The objective of the current study was to characterize the
      expression of the genes for PGE2 receptors (EP2 and EP4) in the horse oviduct
      based upon immunohistochemistry (IHC) and quantitative PCR (qPCR). Oviductal
      tissue was collected from mares at estrus (n=5), at 5 days post-ovulation (n=4),
      and from prepubertal mares (n=5). Isthmic and ampullar regions of the oviduct
      were fixed for IHC or preserved for RNA isolation. Prostaglandin E2 receptors EP2
      and EP4 were strongly expressed by the luminal epithelium of both the isthmic and
      ampullar regions of the horse oviduct with a lesser immuno-expression noted
      within the smooth muscle in both regions of the oviduct. Based upon qPCR,
      relative amounts of EP2 or EP4 mRNA did not differ across estrous cycle stage or
      from prepubertal mares. However, across region and estrous cycle stage, relative
      amount of EP2 was greater (P<0.05) than EP4, and relative amount of EP2 mRNA was
      greater (P<0.001) in the ampullar compared with the isthmic oviduct. The relative
      roles of these receptors in regulating oviduct function in the mare remains to be
      determined.

PMID- 24035157
TI  - Assessment of clinical signs of atopic dermatitis: a systematic review and
      recommendation.
AB  - BACKGROUND: Clinical signs are a core outcome domain for atopic dermatitis (AD)
      trials. The current lack of standardization of outcome measures in AD trials
      hampers evidence-based communication. OBJECTIVE: We sought to provide evidence
      based recommendations for the measurement of clinical signs in AD trials and to
      inform the Harmonising Outcome Measures for Atopic Dermatitis Initiative.
      METHODS: We conducted a systematic review on measurement properties of outcome
      measurements for clinical signs of AD. We systematically searched MEDLINE and
      Embase (until October 1, 2012) for validation studies on instruments measuring
      the clinical signs of AD. Grading of the truth, discrimination, and feasibility
      of scales; methodological study quality; and recommendations were based on
      predefined criteria. RESULTS: Sixteen eligible instruments were identified, of
      which 2 were best validated. The Eczema Area and Severity Index has adequate
      validity, responsiveness, internal consistency, intraobserver reliability, and
      intermediate interobserver reliability but unclear interpretability and
      feasibility. The Severity Scoring of Atopic Dermatitis Index (SCORAD) has
      adequate validity, responsiveness, interobserver reliability, and
      interpretability and unclear intraobserver reliability. Only the objective SCORAD
      (ie, the clinical signs domain of the SCORAD) is internally consistent. The Six
      Area, Six Sign Atopic Dermatitis Index severity score and Three Item Severity
      Score fulfill some quality criteria, but the performance in other required
      measurement properties is unclear. The Patient-oriented Eczema Measure is
      reliable and responsive but has inadequate content validity to assess clinical
      signs of AD. The remaining 11 scales have either (almost) not been validated or
      performed inadequately. CONCLUSIONS: The Eczema Area and Severity Index and
      SCORAD are the best instruments to assess the clinical signs of AD. The other 14
      instruments identified are (currently) not recommended because of unclear or
      inadequate measurement properties.

PMID- 24035158
TI  - Successful cure of C1q deficiency in human subjects treated with hematopoietic
      stem cell transplantation.

PMID- 24035159
TI  - It is not a slide but it is a ladder.

PMID- 24035160
TI  - Meta-analysis of effect of single versus dual antiplatelet therapy on early
      patency of bypass conduits after coronary artery bypass grafting.
AB  - Aspirin monotherapy represents a standard therapy for preserving patency after
      coronary artery bypass grafting. Randomized trials addressing whether dual
      antiplatelet therapy is superior to single antiplatelet therapy to achieve graft
      patency early after coronary surgery have shown inconsistent results. We
      performed a meta-analysis of randomized controlled trials comparing single versus
      dual antiplatelet therapy after coronary artery bypass grafting. In a systematic
      published works search, 5 randomized controlled trials meeting inclusion criteria
      were identified. Pooled efficacy and safety data were abstracted and analyzed
      using a fixed-effects model. The 5 trials included 958 patients and a total of
      2,919 grafts with treatment up to 1 year after coronary bypass surgery. Early
      occlusion was identified in 165 (6.5%) of 2,526 bypass grafts. Early occlusion
      occurred in a greater proportion of grafts among patients treated with single
      therapy (105 of 1,369; 7.7%) compared with dual antiplatelet therapy (69 of
      1,386; 5.0%; p = 0.005). The odds ratio for graft occlusion with single versus
      dual therapy was 1.59 (95% confidence interval 1.16 to 2.17). For vein grafts,
      single antiplatelet therapy was associated with a significantly increased graft
      loss rate (91 of 846; 10.8%) versus dual antiplatelet therapy (57 of 860; 6.6%;
      odds ratio 1.70 [1.20 to 2.40]; p = 0.003). There was no effect on arterial graft
      patency. Bleeding was noted in 3.3% and 4.9% of single and dual therapy treated
      patients, respectively, with only 3 trials reporting bleeding outcomes. In
      conclusion, among 958 patients randomly assigned to either single or dual
      antiplatelet therapy for up to 1 year after coronary bypass surgery, single
      antiplatelet therapy significantly increased the risk for graft occlusion, an
      effect isolated to vein grafts, not arterial grafts.

PMID- 24035161
TI  - Comparison of the reperfusion efficacy of thrombus aspiration with and without
      distal protection during primary percutaneous coronary intervention in patients
      with acute ST-segment elevation myocardial infarction.
AB  - We evaluated a hypothesis that thrombus aspiration with distal protection is
      superior to simple thrombus aspiration in patients treated with primary
      percutaneous coronary intervention (PCI). A total of 176 consecutive patients
      with ST-segment elevation myocardial infarction were enrolled in this study and
      assigned to either the thrombus aspiration group (A, n = 104) or the thrombus
      aspiration with distal protection group using a filter device system (A + DP, n =
      72). We compared the angiographic reperfusion grade, left ventricular (LV)
      function, and clinical outcomes between the 2 groups. There were no significant
      differences in age, gender distribution, the onset-to-reperfusion time, the peak
      levels of creatine kinase, or 6-month mortality between the 2 groups. The rate of
      achieving a Thrombolysis In Myocardial Infarction flow grade of 3 and a
      myocardial blush grade of 3 was higher in the A + DP group than in the A group.
      Among the patients who underwent follow-up catheterization 6 months after PCI (A,
      n = 62; A + DP, n = 52), there were no significant differences in the LV end
      diastolic volume index, LV end-systolic volume index, or LV ejection fraction
      between the 2 groups at the time of PCI or 6 months after PCI. In conclusion,
      thrombus aspiration with distal protection may be more effective in initially
      restoring the coronary blood flow than thrombus aspiration alone, although it may
      not be superior to thrombus aspiration in preventing LV remodeling or preserving
      the LV function in patients with ST-segment elevation myocardial infarction. 

PMID- 24035162
TI  - Heart rate at rest, exercise capacity, and mortality risk in veterans.
AB  - Heart rate (HR) at rest has been associated inversely with mortality risk.
      However, fitness is inversely associated with mortality risk and both increased
      fitness and beta-blockade therapy affect HR at rest. Thus, both fitness and beta
      blockade therapy should be considered when HR at rest-mortality risk association
      is assessed. From 1986 to 2011, we assessed HR at rest, fitness, and mortality in
      18,462 veterans (mean age = 58 +/- 11 years) undergoing a stress test. During a
      median follow-up period of 10 years (211,398 person-years), 5,100 died, at an
      average annual mortality of 24.1 events/1,000 person-years. After adjusting for
      age, body mass index, cardiac risk factors, medication, and exercise capacity, we
      noted approximately 11% increase in risk for each 10 heart beats. To assess the
      risk in a wide and clinically relevant spectrum, we established 6 HR at rest
      categories per 10 heart beat intervals ranging from <60 to >=100 beats. Mortality
      risk was significantly elevated at a HR at rest of >=70 beats/min (hazard ratio
      1.14, confidence interval 1.04 to 1.25; p <0.006) and increased progressively to
      49% (hazard ratio 1.49, confidence interval 1.29 to 1.73; p <0.001) for those
      with a HR at rest of >=100 beats/min. Similar trends were noted when for subjects
      aged <60 and >=60 years and those treated with beta blockers. In all assessments,
      mortality risk was consistently overestimated when fitness was not considered. In
      conclusion, HR at rest-mortality risk association was direct and independent. A
      progressive increase in risk was noted >70 beats/min for the entire cohort, those
      treated with beta blockers, and those aged <60 and >=60 years. Mortality risk was
      overestimated slightly when fitness status was not considered.

PMID- 24035163
TI  - Multidetector row computed tomography parameters associated with paravalvular
      regurgitation after transcatheter aortic valve implantation.
AB  - Multidetector row computed tomographic (MDCT) assessment of aortic annulus
      dimensions and frame position and deployment have been associated with
      paravalvular aortic regurgitation (PAVR) after transcatheter aortic valve
      implantation (TAVI). The present evaluation investigated the (pre- and
      postprocedure) MDCT associates of PAVR >=2+. In total, 123 patients referred for
      TAVI underwent clinical evaluation, transthoracic echocardiography, and pre- and
      post-TAVI MDCT. Pre-TAVI MDCT measurements of the aortic annular dimensions and
      post-TAVI MDCT evaluation of the position and deployment of the prosthesis in the
      native annulus were performed. At 1-month follow-up, PAVR >=2+ was observed in 25
      patients (20%). The difference between the MDCT-derived maximum aortic annulus
      and the nominal diameters of the implanted prosthesis (odds ratio 1.912, p =
      0.002) and shallow position of the frame in the left ventricular outflow tract
      (<2 mm) (odds ratio 4.865, p = 0.017) were independently related to significant
      PAVR. A maximum annulus diameter >=2 mm larger than the nominal frame diameter
      had 72% sensitivity and 61% specificity to predict PAVR. In conclusion, in
      patients undergoing TAVI, >=2-mm difference between maximum aortic annulus and
      nominal prosthesis diameters and depth of the frame into the left ventricular
      outflow tract of <2 mm are independently associated with PAVR >=2+. 

PMID- 24035164
TI  - Aortic stiffness and left ventricular diastolic function in children following
      early repair of aortic coarctation.
AB  - Aortic stiffness and diastolic function are abnormal in adults with repaired
      coarctation of the aorta (CoA). The goal of this study was to determine the
      relation between aortic stiffness and left ventricular (LV) diastolic impairment
      in children who had undergone CoA repair very early in life. This is a
      retrospective review of echocardiograms in children with isolated repaired CoA
      (group CoA; n = 24) and healthy matched controls (group Normal; n = 24). We
      analyzed systolic and LV diastolic functions, proximal and distal ascending
      aortic stiffness indices (SIs), distensibility, and strain. Age range was 0.3 to
      21 (median 9) years. Age at time of CoA repair was 0 to 24 (median 0.5) months.
      Median time since CoA repair was 6 years. There was no significant difference in
      blood pressure, LV size, and systolic function between the groups. LV diastolic
      function was impaired in group CoA compared with group Normal (septal E': CoA
      10.3 +/- 1.6 cm/s and Normal 13.4 +/- 1.9 cm/s, p <0.001). All parameters of
      proximal and distal ascending aortic elasticities were abnormal in group CoA
      versus Normal (SI of proximal ascending aorta: CoA 4.9 +/- 1.6 and Normal 2.7 +/-
      0.6, p <0.001). Across all patients, there was a strong correlation between
      septal E' and proximal ascending aortic SI (r = -0.72, p <0.001). In conclusion,
      even children who underwent CoA repair at a very young age have abnormal LV
      diastolic function and aortic elasticity compared with controls and there is a
      linear relation between the 2. LV diastolic dysfunction in patients with repaired
      CoA may be due to chronically increased afterload. 

PMID- 24035165
TI  - Effects of valsartan versus amlodipine in diabetic hypertensive patients with or
      without previous cardiovascular disease.
AB  - Recently, we reported that angiotensin II receptor blocker (ARB), valsartan, and
      calcium channel blocker (CCB), amlodipine, had similar effects on the prevention
      of cardiovascular disease (CVD) events in diabetic hypertensive patients. We
      assessed the difference of cardiovascular protective effects between ARB and CCB
      in patients with and without previous CVD, respectively. A total of 1,150
      Japanese diabetic hypertensive patients were randomized to either valsartan or
      amlodipine treatment arms, which were additionally divided into 2 groups
      according to the presence of previous CVD at baseline (without CVD, n = 818; with
      CVD, n = 332). The primary composite outcomes were sudden cardiac death, acute
      myocardial infarction, stroke, coronary revascularization, or hospitalization for
      heart failure. The incidence of primary end point events in patients with
      previous CVD was 3.5-times greater than that in patients without previous CVD
      (64.1 vs 17.9/1,000 person-years). The ARB- and the CCB-based treatment arms
      showed similar incidence of composite CVD events in both patients without
      previous CVD (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.76 to 2.40)
      and those with previous CVD (HR 0.79, 95% CI 0.48 to 1.31). The ARB-treatment arm
      showed less incidence of stroke compared with the CCB-based treatment arm in
      patients with previous CVD (HR 0.24, 95% CI 0.05 to 1.11, p = 0.068), whereas the
      2 treatment arms showed similar incidence of stroke in patients without previous
      CVD (HR 1.52, 95% CI 0.59 to 3.91). In conclusion, the ARB- and the CCB-based
      treatments exerted similar protective effects of CVD events regardless of the
      presence of previous CVD. For stroke events, the ARB may have more protective
      effects than the CCB in diabetic hypertensive patients with previous CVD. 

PMID- 24035167
TI  - Association of sympathovagal imbalance with cardiovascular risks in young
      prehypertensives.
AB  - Although cardiovascular (CV) risks have been reported in prehypertension, their
      link to sympathovagal imbalance (SVI) has not been investigated. In the present
      study, we have assessed the factors contributing to SVI and the prediction of CV
      risk by SVI in prehypertensives. Body mass index, CV parameters such as heart
      rate, systolic blood pressure (BP), diastolic BP, mean arterial pressure, rate
      pressure product (RPP), stroke volume, left ventricular ejection time, cardiac
      output, total peripheral resistance, baroreflex sensitivity recorded by
      continuous blood pressure variability monitoring using Finapres, autonomic
      function tests recorded by spectral analysis of heart rate variability (HRV), and
      heart rate and BP responses to standing, deep breathing, and isometric handgrip,
      and biochemical parameters such as homeostatic model assessment of insulin
      resistance, lipid risk factors, inflammatory markers, thyroid profile, and renin
      and oxidative stress parameters were analyzed in young normotensives (n = 118)
      and prehypertensives (n = 58). Contribution of CV risks to low-frequency/high
      frequency (LF/HF) ratio of HRV, the marker of SVI, was determined by multiple
      regression analysis, and prediction of SVI to RPP, a known CV risk, was assessed
      by logisitic regression adjusted for body mass index. BP variability, HRV, and
      autonomic function test parameters were significantly altered in prehypertensives
      and these parameters were correlated with LF/HF. Insulin resistance,
      dyslipidemia, inflammation, and oxidative stress contributed to SVI in
      prehypertensives. LF/HF and baroreflex sensitivity had significant prediction of
      RPP in prehypertensives. In conclusion, SVI in young prehypertensives is due to
      both increased sympathetic and decreased vagal tone. CV risks are linked to SVI
      and SVI predicts cardiac risk in prehypertensives. 

PMID- 24035166
TI  - Mechanisms of functional mitral regurgitation in ischemic cardiomyopathy
      determined by transesophageal echocardiography (from the Surgical Treatment for
      Ischemic Heart Failure Trial).
AB  - The mechanisms underlying functional mitral regurgitation (MR) and the relation
      between mechanism and severity of MR have not been evaluated in a large,
      multicenter, randomized controlled trial. Transesophageal echocardiography (TEE)
      was performed in 215 patients at 17 centers in the Surgical Treatment for
      Ischemic Heart Failure (STICH) trial. Both 2-dimensional (n = 215) and 3
      dimensional (n = 81) TEEs were used to assess multiple quantitative measurements
      of the mechanism and severity of MR. By 2-dimensional TEE, leaflet tenting area,
      anterior and posterior leaflet angles, mitral annulus diameter, left ventricular
      (LV) end-systolic volume index, LV ejection fraction (LVEF), and sphericity index
      (p <0.05 for all) were significantly different across MR grades. By 3-dimensional
      TEE, mitral annulus area, leaflet tenting area, LV end-systolic volume index,
      LVEF, and sphericity index (p <0.05 for all) were significantly different across
      MR grades. A multivariate analysis showed a trend for annulus area (p = 0.069)
      and LV end-systolic volume index (p = 0.071) to predict effective regurgitant
      orifice area and for annulus area (p = 0.018) and LV end-systolic volume index (p
      = 0.073) to predict vena contracta area. In the STICH trial, multiple
      quantitative parameters of the mechanism of functional MR are related to MR
      severity. The mechanism of functional MR in ischemic cardiomyopathy is
      heterogeneous, but no single variable stands out as a strong predictor of
      quantitative severity of MR.

PMID- 24035168
TI  - Effect of extended-release niacin on serum lipids and on endothelial function in
      adults with sickle cell anemia and low high-density lipoprotein cholesterol
      levels.
AB  - Through bound apolipoprotein A-I (apoA-I), high-density lipoprotein cholesterol
      (HDL-C) activates endothelial nitric oxide synthase, inducing vasodilation.
      Because patients with sickle cell disease (SCD) have low apoA-I and endothelial
      dysfunction, we conducted a randomized, double-blinded, placebo-controlled trial
      to test whether extended-release niacin (niacin-ER) increases apoA-I-containing
      HDL-C and improves vascular function in SCD. Twenty-seven patients with SCD with
      levels of HDL-C <39 mg/dl or apoA-I <99 mg/dl were randomized to 12 weeks of
      niacin-ER, increased in 500-mg increments to a maximum of 1,500 mg/day, or
      placebo. The primary outcome was the absolute change in HDL-C level after 12
      weeks, with endothelial function assessed before and at the end of treatment.
      Niacin-ER-treated patients trended to greater increase in HDL-C level compared
      with placebo treatment at 12 weeks (5.1 +/- 7.7 vs 0.9 +/- 3.8 mg/dl, 1-tailed p
      = 0.07), associated with significantly greater improvements in the ratios of low
      density lipoprotein to HDL-C levels (1.24 vs 1.95, p = 0.003) and apolipoprotein
      B to apoA-I levels (0.46 vs 0.58, p = 0.03) compared with placebo-treated
      patients. No improvements were detected in 3 independent vascular physiology
      assays of endothelial function. Thus, the relatively small changes in HDL-C
      levels achieved by the dose of niacin-ER used in our study are not associated
      with improved vascular function in patients with SCD with initially low levels of
      apoA-I or HDL-C.

PMID- 24035169
TI  - Utility of intra-aortic balloon pump support for ventricular septal rupture and
      acute mitral regurgitation complicating acute myocardial infarction.
AB  - Clinical data on optimal management of mechanical complications of myocardial
      infarction are lacking. We retrospectively evaluated the effect of intra-aortic
      balloon pump (IABP) on 30-day survival in patients with postinfarction
      ventricular septal rupture (VSR, n = 55) or acute mitral regurgitation (MR, n =
      26) who developed either cardiogenic shock (n = 46) or severe hemodynamic
      instability that did not fulfill the criteria of shock (n = 35). IABP was
      inserted in 83% of the patients with shock and 57% of those without shock. Thirty
      five (76%) patients with shock and all unstable patients survived until surgical
      repair, which was performed within a median (interquartile range) of 1 (1 to 2)
      and 9 (2 to 18) days from the onset of the complication (p <0.001). All patients
      who did not undergo the operation died within 3 days. Although MR presented more
      acutely, the patients' outcomes were similar to those with VSR. IABP support
      reduced 30-day mortality in the patients with shock (61% vs 100%, p = 0.04) but
      not in the patients without shock (20% vs 27%, p = 0.7). The benefit of IABP
      support in the shock cohort was driven mainly by reduction of preoperative
      mortality (11% vs 88%, p <0.001). Early progression of cardiogenic shock and
      unperformed surgery were the only independent predictors of 30-day mortality
      (hazard ratio 3.4, 95% confidence interval 1.5 to 8 and hazard ratio 5.1, 95%
      confidence interval 2.2 to 11, respectively; p = 0.004 and p <0.001,
      respectively). In conclusion, we suggest that all patients with postinfarction
      VSR or acute MR with signs of cardiogenic shock should immediately receive IABP
      as a bridge to emergent surgical repair. In contrast, hemodynamically unstable
      patients without shock may be first stabilized by medical therapy, without
      additional benefit of IABP, before they undergo cardiac surgery. 

PMID- 24035170
TI  - Effectiveness and safety of spironolactone for systolic heart failure.
AB  - Aldosterone receptor antagonists have been shown in randomized trials to reduce
      morbidity and mortality in adults with symptomatic systolic heart failure. We
      studied the effectiveness and safety of spironolactone in adults with newly
      diagnosed systolic heart failure in clinical practice. We identified all adults
      with newly diagnosed heart failure, left ventricular ejection fraction of <40%,
      and no previous spironolactone use from 2006 to 2008 in Kaiser Permanente
      Northern California. We excluded patients with baseline serum creatinine level of
      >2.5 mg/dl or a serum potassium level of >5.0 mEq/L. We used Cox regression with
      time-varying covariates to evaluate the independent association between
      spironolactone use and death, hospitalization, severe hyperkalemia, and acute
      kidney injury. Among 2,538 eligible patients with a median follow-up of 2.5
      years, 521 patients (22%) initiated spironolactone, which was not associated with
      risk of hospitalization (adjusted hazard ratio 0.91, 95% confidence interval 0.77
      to 1.08) or death (adjusted hazard ratio 0.93, confidence interval 0.60 to 1.44).
      Crude rates of severe hyperkalemia and acute kidney injury during spironolactone
      use were similar to that seen in clinical trials. Spironolactone was
      independently associated with a 3.5-fold increased risk of hyperkalemia but not
      with acute kidney injury. Within a diverse community-based cohort with incident
      systolic heart failure, use of spironolactone was not independently associated
      with risks of hospitalization or death. Our findings suggest that the benefits of
      spironolactone in clinical practice may be reduced compared with other guideline
      recommended medications.

PMID- 24035171
TI  - Comparison of incidence, predictors, and the impact of co-morbidity and
      polypharmacy on the risk of recurrent syncope in patients <85 versus >=85 years
      of age.
AB  - Recurrent syncope is a major cause of hospitalizations and may be associated with
      cardiovascular co-morbidities. Despite this, prognostic factors and the clinical
      characteristics among patients are not well described. Therefore, we identified
      and analyzed data on all patients >50 years of age discharged after a first-time
      episode of syncope in the period 2001 to 2009 through nationwide administrative
      registries. We identified the clinical characteristics of 5,141 patients >=85
      years of age and 23,454 patients <85 years of age. Multivariate Cox models were
      used to assess prognostic factors associated with the end point of recurrent
      syncope according to age. We found that those with syncope and >=85 years were
      more often women (65% vs 47%) and generally had a greater prevalence of
      noncardiovascular co-morbidities, whereas the prevalence of cardiovascular co
      morbidities was more heterogeneously distributed across age groups. Overall,
      significant baseline predictors of recurrent syncope were aortic valve stenosis
      (hazard ratio [HR] 1.48, 95% confidence interval [CI] 1.31 to 1.68), impaired
      renal function (HR 1.34, 95% CI 1.15 to 1.58), atrioventricular or left bundle
      branch block (HR 1.32, 95% CI 1.16 to 1.51), male gender (HR 1.18, 95% CI 1.12 to
      1.24), chronic obstructive pulmonary disorder (HR 1.10, 95% CI 1.02 to 1.19),
      heart failure (HR 1.10, 95% CI 1.02 to 1.21), atrial fibrillation (HR = 1.09, 95%
      CI 1.01 to 1.19), age per 5-year increment (HR 1.09, 95% CI 1.07 to 1.10), and
      orthostatic medications per increase (HR 1.06, 95% CI 1.03 to 1.09). Atrial
      fibrillation and impaired renal function both exhibited less prognostic
      importance for recurrent syncope in the elderly compared with younger population
      (p for interactions <0.01). In conclusion, predictive factors of recurrent
      syncope were closely associated with increased cardiovascular risk profile age
      and gender. The use of multiple orthostatic medications additively increased the
      risk of recurrences representing a need for strategies to reduce unnecessary
      polypharmacy.

PMID- 24035172
TI  - Multilevel temporal Bayesian networks can model longitudinal change in
      multimorbidity.
AB  - OBJECTIVES: Although the course of single diseases can be studied using
      traditional epidemiologic techniques, these methods cannot capture the complex
      joint evolutionary course of multiple disorders. In this study, multilevel
      temporal Bayesian networks were adopted to study the course of multimorbidity in
      the expectation that this would yield new clinical insight. STUDY DESIGN AND
      SETTING: Clinical data of patients were extracted from 90 general practice
      registries in the Netherlands. One and half million patient-years were used for
      analysis. The simultaneous progression of six chronic cardiovascular conditions
      was investigated, correcting for both patient and practice-related variables.
      RESULTS: Cumulative incidence rates of one or more new morbidities rapidly
      increase with the number of morbidities present at baseline, ranging up to 47%
      and 76% for 3- and 5-year follow-ups, respectively. Hypertension and lipid
      disorders, as health risk factors, increase the cumulative incidence rates of
      both individual and multiple disorders. Moreover, in their presence, the observed
      cumulative incidence rates of combinations of cardiovascular disorders, that is,
      multimorbidity differs significantly from the expected rates. CONCLUSION: There
      are clear synergies between health risks and chronic diseases when multimorbidity
      within a patient progresses over time. The method used here supports a more
      comprehensive analysis of such synergies compared with what can be obtained by
      traditional statistics.

PMID- 24035173
TI  - The CARE guidelines: consensus-based clinical case report guideline development.
AB  - BACKGROUND: A case report is a narrative that describes, for medical, scientific,
      or educational purposes, a medical problem experienced by one or more patients.
      Case reports written without guidance from reporting standards are insufficiently
      rigorous to guide clinical practice or to inform clinical study design. PRIMARY
      OBJECTIVE: Develop, disseminate, and implement systematic reporting guidelines
      for case reports. METHODS: We used a three-phase consensus process consisting of
      (1) pre-meeting literature review and interviews to generate items for the
      reporting guidelines, (2) a face-to-face consensus meeting to draft the reporting
      guidelines, and (3) post-meeting feedback, review, and pilot testing, followed by
      finalization of the case report guidelines. RESULTS: This consensus process
      involved 27 participants and resulted in a 13-item checklist-a reporting
      guideline for case reports. The primary items of the checklist are title, key
      words, abstract, introduction, patient information, clinical findings, timeline,
      diagnostic assessment, therapeutic interventions, follow-up and outcomes,
      discussion, patient perspective, and informed consent. CONCLUSIONS: We believe
      the implementation of the CARE (CAse REport) guidelines by medical journals will
      improve the completeness and transparency of published case reports and that the
      systematic aggregation of information from case reports will inform clinical
      study design, provide early signals of effectiveness and harms, and improve
      healthcare delivery.

PMID- 24035174
TI  - Effects of age and lean direction on the threshold of single-step balance
      recovery in younger, middle-aged and older adults.
AB  - Several studies have quantified and compared balance recovery between healthy
      younger and older adults, using a variety of large postural perturbations and
      loss of balance directions. However, to the best of our knowledge, no studies at
      the threshold of balance recovery, where avoiding a fall is not always possible,
      have included middle-aged adults. We thus determined the maximum lean angle from
      which 20 younger, 16 middle-aged and 16 older healthy adults could be suddenly
      released and still recover balance using a single step for forward, sideways and
      backward leans. Results showed that the maximum lean angles of younger adults
      were 23% greater than middle-aged adults and 48% greater than older adults. The
      maximum lean angles for forward leans were 23% greater than sideways leans and
      22% greater than backward leans. These declines with age and lean direction were
      associated with declines in response initiation, execution and geometry. Finally
      exponential regressions showed that the critical ages at which the ability to
      recover balance and avoid a fall significantly decreases were 51.0, 60.6 and 69.9
      yrs for forward, sideways and backward leans, respectively. Therefore, we have
      demonstrated that age affects the ability to recover balance nearly a decade
      earlier than the rate of falls. Future studies should thus not only include older
      adults over 65 yrs, but also middle-aged adults under 65 yrs, or recruit all ages
      from 18 to 85 yrs. Finally, the critical ages identified in this study may
      justify an earlier screening of aging adults to prevent future falls, especially
      the first fall. 

PMID- 24035175
TI  - Effect of calcium or vitamin D supplementation on vascular outcomes: a meta
      analysis of randomized controlled trials.
AB  - BACKGROUND: Whether calcium or vitamin D supplementation reduces serious vascular
      outcomes in older people remains unclear. We conducted a meta-analysis based on
      randomized controlled trials to evaluate the effect of calcium or vitamin D
      supplementation on the risk of major cardiovascular outcomes. METHODS: We
      performed electronic searches in PubMed, Embase, and the Cochrane Library to
      identify relevant randomized controlled trials. Odds ratios (ORs) were used to
      measure the effect of calcium or vitamin D supplementation on the risk of major
      vascular outcomes with a random-effect model. RESULTS: Of the 1643 identified
      studies, we included 11 trials reporting data on 50,252 individuals. These
      studies reported 2685 major cardiovascular events, 1097 events of myocardial
      infarction, and 1350 events of stroke. Calcium or vitamin D supplementation did
      not have an effect on major cardiovascular events (OR, 1.03; 95% confidence
      interval [CI]: 0.94-1.12; P=0.54), myocardial infarction (OR, 1.08; 95% CI: 0.96
      1.22; P=0.21), or stroke (OR, 1.01; 95% CI: 0.91-1.13; P=0.80) when compared to
      the effect with a placebo. Subgroup analysis indicated that calcium
      supplementation alone might play an important role in increasing the risk of
      major cardiovascular events, myocardial infarction, and stroke, but this
      difference could not be identified as statistically significant. Furthermore,
      males seem to experience more harmful effects with supplements of calcium or
      vitamin D than the effects experienced by females. CONCLUSIONS: Calcium
      supplementation might increase the risk of major cardiovascular events,
      myocardial infarction, and stroke compared to the risk with a placebo.

PMID- 24035176
TI  - Basal stress cardiomyopathy induced by exogenous catecholamines in younger
      adults.

PMID- 24035177
TI  - Effects of left atrial strain on functional capacity in chronic severe mitral
      regurgitation.

PMID- 24035179
TI  - [Clitoral epidermoid cyst causing clitoromegaly. A rare case report].
AB  - Clitoromegaly is uncommon. It is mostly congenital, hormonal or tumoral.
      Epidermoid cyst is rare. It can be the consequence of trauma, but in some
      situations the cyst can be non-traumatic. We report the case of a 53-year-old
      woman who presented a misdiagnosis of clitoromegaly due to hormonal condition.
      Surgical exploration has highlighted an epidermoid cyst. This observation
      underlines the importance to evoke a cystic origin for clitoral hypertrophy and
      encourages us to propose imaging (ultrasound, MRI) in case of etiological doubt.
      The preoperative diagnosis must be made to preserve vascularization and
      innervation of the clitoris. 

PMID- 24035178
TI  - Reduced anterior cingulate gray matter volume and thickness in subjects with
      deficit schizophrenia.
AB  - BACKGROUND: Patients with deficit schizophrenia (D-SZ) differ from patients with
      the non-deficit form of schizophrenia (ND-SZ) in several aspects such as risk
      factors, neurobiological correlates, treatment response and clinical outcome. It
      has been debated if brain morphology could differentiate D-SZ from ND-SZ.
      Anterior cingulate gyrus (ACG) region regulates cognitive and emotional
      processing and past studies reported structural changes in this region in
      patients with SZ. METHODS: 1.5-T 3D MRI scans were obtained from 18 D-SZ
      patients, 30 ND-SZ patients and 82 healthy controls (HCs). We used FreeSurfer
      initalized labeled cortical distance mapping (FSLCDM) to measure ACG gray matter
      volume, cortical thickness, and area of the gray/white interface. Furthermore,
      cortical thickness was compared among the 3 groups using the pooled labeled
      cortical distance mapping (LCDM) method. RESULTS: The ACG cortex of the D-SZ
      group was thinner than the ND-SZ group. Pooled LCDM demonstrated that the ACG
      cortex was bilaterally thinner in both the ND-SZ group and the D-SZ group
      compared with the control group. The right ACG gray matter volume was
      significantly reduced in D-SZ patients as compared with healthy controls (p=0.005
      CONCLUSION: Our data suggest that qualitative, categorical differences in
      neuroanatomy may distinguish between deficit and non-deficit subtypes of
      schizophrenia.

PMID- 24035180
TI  - [Use of a submental flap for reconstruction of both lips in a complex case of
      mutilation].
AB  - Authors present a new technique allowing simultaneous reconstruction of both
      lips. In a severe mutilation, a submental flap pedicled on both submental axes
      was used. Three weeks after the operation, an horizontal incision was done into
      the flap combined with full thickness skin grafts to achieve the reconstruction
      of both labial esthetic units. The other available techniques are discussed,
      among them, microsurgery. This technique seemed very relevant in this
      reconstruction and a good example of Gillies' principle: "replace like with
      like".

PMID- 24035181
TI  - Spontaneously occurring restrictive nonhypertrophied cardiomyopathy in domestic
      cats: a new animal model of human disease.
AB  - BACKGROUND: Spontaneously occurring small animal models of myocardial disease,
      closely resembling the human condition, have been reported for hypertrophic
      cardiomyopathy (in cats) and arrhythmogenic right ventricular cardiomyopathy (in
      cats and boxer dogs). Nonhypertrophied restrictive cardiomyopathy (RCM) is a well
      recognized but relatively uncommon primary heart muscle disease causing
      substantial morbidity in humans. We describe RCM occurring in felines here as a
      potential model of human disease. METHODS: We used two-dimensional and Doppler
      echocardiography to define morphologic and functional features of RCM in 35
      domestic cats (25 male; 10+/-4 years old) presenting to a subspecialty veterinary
      clinic. Ten underwent complete necropsy examination. Echocardiographic parameters
      of diastolic filling were compared to those in 41 normal controls. RESULTS: The
      35 cats presented with congestive heart failure (n=32), lethargy (n=2), or
      syncope (n=1), associated with thromboembolism in 5 and supraventricular
      tachyarrhythmias in 8. During an average 4.4-year follow-up period, 18 died or
      were euthanized due to profound heart failure, and 3 died suddenly; survival from
      clinical presentation to death was 0.1 to 52 months. Echocardiographic and
      necropsy examination showed biatrial enlargement, nondilated ventricular
      chambers, and normal wall thicknesses and atrioventricular valves. Histopathology
      demonstrated disorganized myocyte architecture and patchy replacement myocardial
      fibrosis. Pulsed Doppler demonstrated restrictive physiology with increased early
      (E) mitral filling velocity (1.1+/-0.3 m/s) and peak E to peak late (A) flow
      ratios (4.3+/-1.2), reduced A filling velocity (0.3+/-0.1 m/s), and shortened
      mitral deceleration time (40.7+/-9.3 ms; all P<.001 vs. controls), with preserved
      left ventricular systolic function. CONCLUSIONS: A primary myocardial disease
      occurring spontaneously in domestic cats is remarkably similar to restrictive
      nondilated and nonhypertrophied cardiomyopathy in man and represents another
      potential animal model for human disease.

PMID- 24035182
TI  - Relapse of hepatitis C in three immunocompetent patients achieved a sustained
      virological response following interferon-based antiviral therapy.

PMID- 24035183
TI  - Case presentation of soft tissue parapharyngeal chondroma in a pediatric patient.
AB  - Soft tissue chondromas are uncommon benign tumors found mostly in the hands and
      feet and rarely reported in the pediatric population. In this case presentation
      we describe a 10 year old boy who had an MRI for facial paralysis due to Ramsey
      Hunt Syndrome, which incidentally revealed a parapharyngeal mass. He underwent
      transoral resection of the mass without complication, and histopathology
      confirmed the diagnosis of soft tissue chondroma. This case is unique due to the
      unusual location of the tumor and its presentation in a child.

PMID- 24035184
TI  - Hearing gain with a BAHA test-band in patients with single-sided deafness.
AB  - PURPOSE: It is assumed that preoperative use of a bone-anchored hearing aid
      (BAHA) test-band will give a patient lower gain compared to real post-operative
      gain because of the reduction of energy through the scalp when using a test-band.
      Hearing gains using a BAHA test-band were analyzed in patients with unilateral
      hearing loss. MATERIALS AND METHODS: Nineteen patients with unilateral
      sensorineural hearing loss were enrolled. A test-band, which was connected to
      BAHA Intenso with full-on gain, was put on the mastoid. Conventional air
      conduction (AC) pure-tone averages (PTAs) and sound-field PTAs and speech
      reception thresholds (SRTs) were obtained in conditions A (the better ear naked),
      B (the better ear plugged), and C (the better ear plugged with a test-band on the
      poorer mastoid). RESULTS: Air-conduction PTAs of the poorer and better ears were
      91 +/- 19 and 18 +/- 8 dB HL. Sound-field PTAs in condition B were higher than
      those in condition A (54 vs. 26 dB HL), which means that earplugs can block the
      sound grossly up to 54 dB HL through the better ears. The aided PTAs (24 +/- 6 dB
      HL) in condition C were similar to those of the better ears in condition A (26+/
      9 dB HL), though condition C showed higher thresholds at 500 Hz and lower
      thresholds at 1 and 2kHz when compared to condition A. The hearing thresholds
      using a test-band were similar to the published results of BAHA users with the
      volume to most comfortable level (MCL). CONCLUSION: Our findings showed that a
      BAHA test-band on the poorer ear could transmit sound to the cochlea as much as
      the better ears can hear. The increased functional gain at 1 and 2kHz reflects
      the technical characteristics of BAHA processor. The reduction of energy through
      the scalp when using a test-band seems to be offset by the difference of output
      by setting the volume to full-on gain and using a high-powered speech processor.
      Preoperative hearing gains using a test-band with full-on gain seems to be
      similar to the post-operative gains of BAHA users with the volume to MCL.

PMID- 24035185
TI  - Facilitators and barriers in treatment seeking for cannabis dependence.
AB  - BACKGROUND: Relatively few cannabis dependent people seek treatment and little is
      known about determinants of treatment seeking. METHODS: Treatment determinants
      were compared among 70 DSM-IV cannabis dependent patients and 241 non-treatment
      seeking DSM-IV cannabis dependent community subjects. In addition, perceived
      facilitators for treatment seeking were assessed in patients, whereas perceived
      barriers were assessed in 160/241 cannabis dependent community subjects not
      prepared to seek treatment (precluders), of whom 63/160 showed an objective
      treatment need, and 30/241 showed a subjective treatment need. RESULTS: Compared
      to non-treatment seekers, patients reported more cannabis use (176.9 versus 82.8
      joints monthly), more symptoms of dependence (5.6 versus 4.5), higher perceived
      lack of social support (70.0% versus 41.1%), more pressure to seek treatment
      (58.6% versus 21.6%), a more positive attitude to treatment, and more previous
      treatments. In addition, patients reported more mental health problems
      (internalising disorders 57.1% versus 24.5%; externalising disorders 52.9% versus
      35.3%) and more functional impairments (8.4 versus 4.8 monthly days out of role).
      Cannabis dependent 'precluders' reported desire for self-reliance (50.0%),
      preference for informal help (22.5%), and absent treatment need (16.9%) as their
      main reasons not to seek treatment, whereas cannabis dependent community subjects
      with a subjective treatment need mainly expressed desire for self-reliance
      (36.7%), treatment ineffectiveness (16.7%), and avoiding stigma (13.3%).
      CONCLUSIONS: Functional impairment, mental health problems and social pressure
      are important reasons to seek treatment in people with cannabis dependence.
      Treatment participation might improve if desire for self-reliance and the
      preference for informal help are considered, and perceived ineffectiveness of
      treatment and stigmatisation are publicly addressed.

PMID- 24035187
TI  - Response to "RE: Response to 'Acupuncture: it is time for scientifically well
      designed study'".

PMID- 24035186
TI  - Reductions in circulating endocannabinoid levels in individuals with post
      traumatic stress disorder following exposure to the World Trade Center attacks.
AB  - Endocannabinoid (eCB) signaling has been identified as a modulator of adaptation
      to stress, and is integral to basal and stress-induced glucocorticoid regulation.
      Furthermore, interactions between eCBs and glucocorticoids have been shown to be
      necessary for the regulation of emotional memories, suggesting that eCB function
      may relate to the development of post-traumatic stress disorder (PTSD). To
      examine this, plasma eCBs were measured in a sample (n=46) drawn from a
      population-based cohort selected for physical proximity to the World Trade Center
      (WTC) at the time of the 9/11 attacks. Participants received a structured
      diagnostic interview and were grouped according to whether they met diagnostic
      criteria for PTSD (no PTSD, n=22; lifetime diagnosis of PTSD=24). eCB content (2
      arachidonoylglycerol (2-AG) and anandamide (AEA)) and cortisol were measured from
      8 a.m. plasma samples. Circulating 2-AG content was significantly reduced among
      individuals meeting diagnostic criteria for PTSD. The effect of reduced 2-AG
      content in PTSD remained significant after controlling for the stress of exposure
      to the WTC collapse, gender, depression and alcohol abuse. There were no
      significant group differences for AEA or cortisol levels; however, across the
      whole sample AEA levels positively correlated with circulating cortisol, and AEA
      levels exhibited a negative relationship with the degree of intrusive symptoms
      within the PTSD sample. This report shows that PTSD is associated with a
      reduction in circulating levels of the eCB 2-AG. Given the role of 2-AG in the
      regulation of the stress response, these data support the hypothesis that
      deficient eCB signaling may be a component of the glucocorticoid dysregulation
      associated with PTSD. The negative association between AEA levels and intrusive
      symptoms is consistent with animal data indicating that reductions in AEA promote
      retention of aversive emotional memories. Future work will aim to replicate these
      findings and extend their relevance to clinical pathophysiology, as well as to
      neuroendocrine and molecular markers of PTSD. 

PMID- 24035188
TI  - Clinical implications of T790M mutation in patients with acquired resistance to
      EGFR tyrosine kinase inhibitors.
AB  - OBJECTIVES: Although T790M mutation is considered to be the major mechanism of
      acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase
      inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC), its
      clinical implication remains undetermined. METHODS: Post-progression tumor
      specimens were prospectively collected for T790M mutation analysis in NSCLC
      patients with acquired resistance to initial EGFR TKIs. Clinical features were
      compared between patients with and without T790M. RESULTS: Out of 70 cases, 36
      (51%) were identified to have T790M mutation in the rebiopsy specimen. There was
      no difference in the pattern of disease progression, progression-free survival
      for initial TKIs (12.8 and 11.3 months), post-progression survival (14.7 and 14.1
      months), or overall survival (43.5 and 36.8 months) in patients with and without
      T790M. In total, 34 patients received afatinib after post-progression biopsy as a
      subsequent treatment, and the response rate was 18%. The median progression-free
      survival for afatinib was 3.7 months for the entire group, and 3.2 and 4.6 months
      for the groups with and without T790M, respectively (P = 0.33). CONCLUSIONS: The
      identification of T790M as acquired resistance mechanism was clinically feasible.
      Although T790M had no prognostic or predictive role in the present study, further
      research is necessary to identify patients with T790M-mutant tumors who might
      benefit from newly developed T790M-specific TKIs.

PMID- 24035189
TI  - Treatment of patients with pulmonary arterial hypertension at the time of death
      or deterioration to functional class IV: insights from the REVEAL Registry.
AB  - BACKGROUND: Current guidelines recommend intravenous prostacyclin as first-line
      therapy for patients with pulmonary arterial hypertension (PAH) in New York Heart
      Association/World Health Organization functional class (FC) IV, or combination
      therapy for patients in any FC who do not respond to monotherapy. We investigated
      the aggressiveness of therapy in patients enrolled in the REVEAL (Registry to
      Evaluate Early and Long-Term PAH Disease Management) Registry who deteriorated to
      FC IV or died. METHODS: Among 3,515 patients (age >= 18 years) in REVEAL with a
      mean pulmonary artery pressure >= 25 mm Hg and pulmonary capillary wedge pressure
      <= 15 mm Hg, we examined three sub-sets: the 487 patients who had a PAH-related
      death, the larger set of 908 patients who died from any cause (PAH-related, not
      PAH-related, or unknown), and the 294 patients who were FC I, II, or III at
      enrollment and later assessed as FC IV. RESULTS: Among patients who died, 56% (n
      = 272 of 487) and 43% (n = 391 of 908) were receiving intravenous prostacyclin
      before death in the PAH-related death and all-cause death cohorts, respectively.
      In the PAH-related death cohort, 60% and 16% of patients were most recently
      assessed as FC III and IV, respectively; among those assessed as FC IV within 6
      months of death, 57.7% (n = 15 of 26) had received intravenous prostacyclin.
      Because many patients died without an observed assessment of worsening to FC IV,
      we also evaluated medication use among the cohort of patients who worsened to FC
      IV during the study. One day before worsening to FC IV, 150 of 294 patients were
      not receiving intravenous prostacyclin and 70 were receiving only PAH-specific
      monotherapy; of these, 61% and 67%, respectively, received no additional therapy
      90 days later. CONCLUSIONS: Intravenous prostacyclin and combination therapy are
      not consistently used in the most seriously ill patients enrolled in REVEAL after
      being assessed as FC IV or at the time of death.

PMID- 24035190
TI  - A new title to an old song: some observations on the conduct of meta-analyses.
AB  - The purpose of this commentary is to draw attention to some unsatisfactory
      features in the way that meta-analyses are presented in assisted reproduction
      journals. These features will be illustrated with reference to recently published
      papers. An appeal will be made for a more fastidious and rigorous approach to
      this statistical technique that has become a ubiquitous part of the research
      effort in assisted reproduction treatment. 

PMID- 24035191
TI  - Identical pathogenesis and neuropathological phenotype of scrapie in valine,
      arginine, glutamine/valine, arginine, glutamine sheep infected experimentally by
      the oral and conjunctival routes.
AB  - The pathogenesis of scrapie in sheep after natural or oral exposure to the
      infectious agent generally involves the early accumulation of disease-associated
      prion protein (PrP(d)) in the lymphoreticular system (LRS). This phase is
      followed by neuroinvasion, for which two routes, ascending neural and
      haematogenous, have been postulated. The present study reports the use of
      immunohistochemistry to track the tissue progression of PrP(d) deposition in
      sheep of a single, highly scrapie-susceptible PrP genotype administered by the
      oral or conjunctival routes. Regardless of the route of infection, the earliest
      detection of PrP(d) was in gut- and pharynx-associated LRS tissues. Subsequently,
      the brain became PrP(d) positive simultaneously with other LRS tissues, but
      before the spinal cord and peripheral nervous tissues of the enteric,
      parasympathetic and sympathetic systems. The sites of initial PrP(d) accumulation
      in the brain were the dorsal motor nucleus of the vagus and the hypothalamus and
      their related circumventricular organs (the area postrema and the median
      eminence, respectively). These were the same for both routes of infection. Rapid
      progression to clinical disease was observed in sheep infected orally or
      conjunctivally, with definite signs of scrapie recorded at around 6 and 8 months
      after infection, respectively. Longer incubation periods in sheep infected by the
      conjunctival route were probably due to them receiving a lower dose than those
      infected orally. Irrespective of the route of infection, clinically affected
      sheep showed the same pathological phenotype (PrP(d) profile) and PrP(d)
      distribution throughout the brain. The identical peripheral and central
      pathogenesis observed in sheep of both groups suggests early dissemination of the
      infectious agent in the bloodstream and a common neuroinvasion pathway. The late
      involvement of the enteric and autonomic nervous system supports a haematogenous
      route of infection to the brain. 

PMID- 24035193
TI  - Mutations in GMPPA cause a glycosylation disorder characterized by intellectual
      disability and autonomic dysfunction.
AB  - In guanosine diphosphate (GDP)-mannose pyrophosphorylase A (GMPPA), we identified
      a homozygous nonsense mutation that segregated with achalasia and alacrima,
      delayed developmental milestones, and gait abnormalities in a consanguineous
      Pakistani pedigree. Mutations in GMPPA were subsequently found in ten additional
      individuals from eight independent families affected by the combination of
      achalasia, alacrima, and neurological deficits. This autosomal-recessive disorder
      shows many similarities with triple A syndrome, which is characterized by
      achalasia, alacrima, and variable neurological deficits in combination with
      adrenal insufficiency. GMPPA is a largely uncharacterized homolog of GMPPB. GMPPB
      catalyzes the formation of GDP-mannose, which is an essential precursor of glycan
      moieties of glycoproteins and glycolipids and is associated with congenital and
      limb-girdle muscular dystrophies with hypoglycosylation of alpha-dystroglycan.
      Surprisingly, GDP-mannose pyrophosphorylase activity was unchanged and GDP
      mannose levels were strongly increased in lymphoblasts of individuals with GMPPA
      mutations. This suggests that GMPPA might serve as a GMPPB regulatory subunit
      mediating feedback inhibition of GMPPB instead of displaying catalytic enzyme
      activity itself. Thus, a triple-A-like syndrome can be added to the growing list
      of congenital disorders of glycosylation, in which dysregulation rather than mere
      enzyme deficiency is the basal pathophysiological mechanism. 

PMID- 24035192
TI  - Human SNP links differential outcomes in inflammatory and infectious disease to a
      FOXO3-regulated pathway.
AB  - The clinical course and eventual outcome, or prognosis, of complex diseases
      varies enormously between affected individuals. This variability critically
      determines the impact a disease has on a patient's life but is very poorly
      understood. Here, we exploit existing genome-wide association study data to gain
      insight into the role of genetics in prognosis. We identify a noncoding
      polymorphism in FOXO3A (rs12212067: T > G) at which the minor (G) allele, despite
      not being associated with disease susceptibility, is associated with a milder
      course of Crohn's disease and rheumatoid arthritis and with increased risk of
      severe malaria. Minor allele carriage is shown to limit inflammatory responses in
      monocytes via a FOXO3-driven pathway, which through TGFbeta1 reduces production
      of proinflammatory cytokines, including TNFalpha, and increases production of
      anti-inflammatory cytokines, including IL-10. Thus, we uncover a shared genetic
      contribution to prognosis in distinct diseases that operates via a FOXO3-driven
      pathway modulating inflammatory responses.

PMID- 24035194
TI  - Transmission disequilibrium of small CNVs in simplex autism.
AB  - We searched for disruptive, genic rare copy-number variants (CNVs) among 411
      families affected by sporadic autism spectrum disorder (ASD) from the Simons
      Simplex Collection by using available exome sequence data and CoNIFER (Copy
      Number Inference from Exome Reads). Compared to high-density SNP microarrays, our
      approach yielded ~2* more smaller genic rare CNVs. We found that affected
      probands inherited more CNVs than did their siblings (453 versus 394, p = 0.004;
      odds ratio [OR] = 1.19) and that the probands' CNVs affected more genes (921
      versus 726, p = 0.02; OR = 1.30). These smaller CNVs (median size 18 kb) were
      transmitted preferentially from the mother (136 maternal versus 100 paternal, p =
      0.02), although this bias occurred irrespective of affected status. The excess
      burden of inherited CNVs among probands was driven primarily by sibling pairs
      with discordant social-behavior phenotypes (p < 0.0002, measured by Social
      Responsiveness Scale [SRS] score), which contrasts with families where the
      phenotypes were more closely matched or less extreme (p > 0.5). Finally, we found
      enrichment of brain-expressed genes unique to probands, especially in the SRS
      discordant group (p = 0.0035). In a combined model, our inherited CNVs, de novo
      CNVs, and de novo single-nucleotide variants all independently contributed to the
      risk of autism (p < 0.05). Taken together, these results suggest that small
      transmitted rare CNVs play a role in the etiology of simplex autism. Importantly,
      the small size of these variants aids in the identification of specific genes as
      additional risk factors associated with ASD. 

PMID- 24035195
TI  - Fibroblast growth factor-2 expression in the preimplantation equine conceptus and
      endometrium of pregnant and cyclic mares.
AB  - Uterine-derived growth factors and cytokines play essential roles in regulating
      preimplantation conceptus development. In several species, fibroblast growth
      factor-2 (FGF2) promotes embryogenesis, trophoblast cell migration, and adhesion.
      This study investigated mRNA expression for FGF2, its receptors (FGFR1-4), the
      activating factor FGF binding protein (FGF-BP) in equine endometrium and
      trophectoderm during early pregnancy and the estrous cycle, and localized FGF2
      protein in both endometrium and conceptus tissues. FGF2, FGFRs1-4, and FGFBP
      mRNAs were expressed in endometrium throughout the estrous cycle and early
      pregnancy, and in days 14 to 28 conceptus membranes. FGF2 transcription was
      higher during estrus than on days 7 or 14 of diestrus, suggesting estrogen
      dependency. Endometrial expression of FGF2 mRNA and protein increased as
      pregnancy progressed from days 21 and day 28; FGF2 protein was localized
      predominantly in the luminal and glandular epithelium. FGF2 mRNA was detectable
      in trophectoderm from as early as day 14, and transcription and translation
      increased in day 21 and 28 allantochorion. FGF2 protein was localized mainly in
      the trophectoderm up to day 21 but was present in both trophectoderm and endoderm
      of day 28 allantochorion. FGFR1 mRNA was down-regulated in the endometrium at day
      7 of diestrus but increased again by day 14. Gene expression for all of the FGFR2
      splice variants, including FGFR2IIIc, was up-regulated during estrus. During
      early pregnancy, endometrial FGFR1 expression decreased, whereas FGFR2IIIc
      expression did not change. Conceptus mRNA expression for all FGFRs increased as
      pregnancy progressed. FGFBP expression remained unchanged in endometrium, but
      increased in the conceptus between days 14 and 28, suggesting a role in
      regulating FGF2 activity in the developing conceptus. We conclude that during
      weeks 3 and 4 of pregnancy, the equine endometrial epithelium produces FGF2,
      which may play a role in trophoblast development and adhesion. 

PMID- 24035196
TI  - Antiphospholipid antibodies internalised by human syncytiotrophoblast cause
      aberrant cell death and the release of necrotic trophoblast debris.
AB  - Antiphospholipid antibodies (aPL) are the strongest maternal risk factor for pre
      eclampsia, a hypertensive disease of human pregnancy. Pre-eclampsia is triggered
      by a toxic factor released from the placenta that activates the maternal
      endothelium. Antiphospholipid antibodies cause the release of necrotic
      trophoblast debris from the placental syncytiotrophoblast and this debris can
      activate endothelial cells. In this study, we investigated how aPL affects
      syncytiotrophoblast death and production of necrotic trophoblast debris by
      examining the interaction between aPL and human first trimester placental
      explants. Human polyclonal and murine monoclonal aPL, but not control antibodies,
      were rapidly internalised by the syncytiotrophoblast. Inhibitors of endocytosis
      or the low-density lipoprotein receptor (LDLR) family, but not toll-like
      receptors, decreased the internalisation of aPL and prevented the release of
      necrotic trophoblast debris from the syncytiotrophoblast. Once internalised, aPL
      increased inner mitochondrial membrane leak and Cytochrome c release while
      depressing oxidative flux through Complex IV of the electron transport system in
      syncytiotrophoblast mitochondria. These data suggest that the human
      syncytiotrophoblast internalises aPL by antigen-dependent endocytosis involving
      LDLR family members. Once internalised by the syncytiotrophoblast, aPL affects
      the death-regulating mitochondria, causing extrusion of necrotic trophoblast
      debris which can activate maternal endothelial cells thereby contributing to the
      pathogenesis of pre-eclampsia.

PMID- 24035197
TI  - Autoimmune hepatitis: Contrasts and comparisons in children and adults - a
      comprehensive review.
AB  - This review concentrates on autoimmune hepatitis (AIH), a liver disorder
      affecting both children and adults, characterized by inflammatory liver
      histology, elevated transaminase levels, circulating non-organ-specific
      autoantibodies, and increased levels of immunoglobulin G, in the absence of a
      known aetiology. Two types of AIH are recognized according to seropositivity:
      smooth muscle antibody and/or antinuclear antibody define AIH type 1, while
      antibodies to liver-kidney microsome type 1 and/or liver cytosol type 1 define
      AIH type 2. AIH type 1 affects both adults and children, while AIH type 2 is
      mainly a paediatric disease, though it does occasionally affects young adults.
      There is a female predominance in both types. AIH is particularly aggressive in
      children/adolescents, progressing rapidly unless immunosuppressive treatment is
      started promptly. With appropriate treatment 80% of patients achieve remission
      and long-term survival. In childhood/adolescence, sclerosing cholangitis with
      strong autoimmune features, including interface hepatitis and serological
      features identical to AIH type 1, is as prevalent as AIH, but it affects boys and
      girls equally. The differential diagnosis relies on cholangiographic studies. In
      autoimmune sclerosing cholangitis, liver parenchymal damage responds
      satisfactorily to immunosuppressive treatment, whereas bile duct disease
      progresses in 50% of cases, leading to a worse prognosis and higher
      transplantation requirement; it has a higher recurrence rate after transplant
      than AIH. AIH can arise de novo in patients transplanted for non-autoimmune liver
      disease. Post transplant de novo AIH affects children and adults and responds
      well to the same treatment schedule used for classical AIH, but not to that used
      for acute rejection. 

PMID- 24035198
TI  - Trimethoprim/sulfamethoxazole susceptibility of Mycobacterium tuberculosis.

PMID- 24035199
TI  - Looking beside the fracture.

PMID- 24035201
TI  - A comparison of the reliability of the trochanteric prominence angle test and the
      alternative method in healthy subjects.
AB  - A wide range of intra- and inter-rater reliabilities of the trochanteric
      prominence angle test (TPAT) has been reported. We introduced the transcondylar
      angle test (TCAT) as an alternative to the TPAT and using a smartphone as a
      reliable measurement tool for femoral neck anteversion (FNA) measurement. The
      reliabilities of the TPAT and the TCAT, the reliability of using a smartphone as
      a clinical measurement tool, and the correlation between the difference value of
      medial knee joint space (KJS) between rest and tested positions and the
      difference value between the TPAT and TCAT were assessed. Two physical therapists
      independently determined the reliabilities of the TPAT with a digital
      inclinometer, the TCAT with a digital inclinometer, and the TCAT with a
      smartphone in 19 hips of 10 healthy subjects (5 male and 5 female, 22.2 +/- 1.69
      years). The medial KJS in rest and the tested position were assessed using a
      sonography. The intra-class correlation coefficients (ICC) for the intra-rater
      reliabilities of TPAT with a digital inclinometer (ICC = 0.92), TCAT with a
      digital inclinometer (ICC = 0.94) and a smartphone (ICC = 0.95) in both testers
      were substantial. The inter-rater reliability of TPAT with a digital inclinometer
      was fair (ICC = 0.48) while TCAT with a digital inclinometer (ICC = 0.89) and a
      smartphone (ICC = 0.85) were substantial. The correlation between the difference
      value of medial KJS between rest and tested positions and the difference value
      between TPAT and TCAT was low and statistically non-significant (r = 0.114; p =
      0.325). The TCAT would be more reliable than the TPAT in inter-rater test. Using
      a smartphone is a clinically comparable measuring tool to a digital inclinometer.

PMID- 24035200
TI  - Dynamics of enzymatic interactions during short flap human Okazaki fragment
      processing by two forms of human DNA polymerase delta.
AB  - Lagging strand DNA replication requires the concerted actions of DNA polymerase
      delta, Fen1 and DNA ligase I for the removal of the RNA/DNA primers before
      ligation of Okazaki fragments. To better understand this process in human cells,
      we have reconstituted Okazaki fragment processing by the short flap pathway in
      vitro with purified human proteins and oligonucleotide substrates. We
      systematically characterized the key events in Okazaki fragment processing: the
      strand displacement, Pol delta/Fen1 combined reactions for removal of the RNA/DNA
      primer, and the complete reaction with DNA ligase I. Two forms of human DNA
      polymerase delta were studied: Pol delta4 and Pol delta3, which represent the
      heterotetramer and the heterotrimer lacking the p12 subunit, respectively. Pol
      delta3 exhibits very limited strand displacement activity in contrast to Pol
      delta4, and stalls on encounter with a 5'-blocking oligonucleotide. Pol delta4
      and Pol delta3 exhibit different characteristics in the Pol delta/Fen1 reactions.
      While Pol delta3 produces predominantly 1 and 2 nt cleavage products irrespective
      of Fen1 concentrations, Pol delta4 produces cleavage fragments of 1-10 nts at low
      Fen1 concentrations. Pol delta3 and Pol delta4 exhibit comparable formation of
      ligated products in the complete system. While both are capable of Okazaki
      fragment processing in vitro, Pol delta3 exhibits ideal characteristics for a
      role in Okazaki fragment processing. Pol delta3 readily idles and in combination
      with Fen1 produces primarily 1 nt cleavage products, so that nick translation
      predominates in the removal of the blocking strand, avoiding the production of
      longer flaps that require additional processing. These studies represent the
      first analysis of the two forms of human Pol delta in Okazaki fragment
      processing. The findings provide evidence for the novel concept that Pol delta3
      has a role in lagging strand synthesis, and that both forms of Pol delta may
      participate in DNA replication in higher eukaryotic cells. 

PMID- 24035202
TI  - MtDNA depletions and deletions may also be important in pathogenesis of lung
      cancer.

PMID- 24035203
TI  - Physiologic response to various levels of pressure support and NAVA in prolonged
      weaning.
AB  - Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation wherein the
      delivered assistance is proportional to diaphragm electrical activity (EAdi)
      throughout inspiration. We assessed the physiologic response to varying levels of
      NAVA and pressure support ventilation (PSV) in 13 tracheostomised patients with
      prolonged weaning. Each patient randomly underwent 8 trials, at four levels of
      assistance either in PSV and NAVA. i - high (no dyspnoea and/or distress); iv -
      low (associated with dyspnoea and/or distress; ii and iii - at ~75% and ~25% of
      the difference between high and low support respectively. We measured tidal
      volume (VT), peak EAdi, (EAdipeak) and airway pressure, ineffective efforts and
      breathing pattern variability. With both NAVA and PSV, decreasing assistance
      resulted in parallel significant increase in EAdipeak associated with a
      concomitant reduction in VT and minute ventilation in PSV, but not in NAVA. VT
      variability significantly increased when reducing ventilatory assistance in PSV
      only, while remained unchanged varying the NAVA level. The ineffective triggering
      index was not significantly different between the two modes. In patients with
      prolonged weaning, with the specific settings adopted, compared to PSV, NAVA
      reduced the risk of over-assistance and overall improved patient-ventilator
      interaction, while not significantly affecting patient-ventilator synchrony. 

PMID- 24035204
TI  - Insight into the relationship between brain/behavioral speed and variability in
      patients with minimal hepatic encephalopathy.
AB  - OBJECTIVE: Intra-individual variability (IIV) of response reaction times (RTs)
      and psychomotor slowing were proposed as markers of brain dysfunction in patients
      with minimal hepatic encephalopathy (MHE), a subclinical disorder of the central
      nervous system frequently detectable in patients with liver cirrhosis. However,
      behavioral measures alone do not enable investigations into the neural correlates
      of these phenomena. The aim of this study was to investigate the
      electrophysiological correlates of psychomotor slowing and increased IIV of RTs
      in patients with MHE. METHODS: Event-related potentials (ERPs), evoked by a
      stimulus-response (S-R) conflict task, were recorded from a sample of patients
      with liver cirrhosis, with and without MHE, and a group of healthy controls. A
      recently presented Bayesian approach was used to estimate single-trial P300
      parameters. RESULTS: Patients with MHE, with both psychomotor slowing and higher
      IIV of RTs, showed higher P300 latency jittering and lower single-trial P300
      amplitude compared to healthy controls. In healthy controls, distribution
      analysis revealed that single-trial P300 latency increased and amplitude
      decreased as RTs became longer; however, in patients with MHE the linkage between
      P300 and RTs was weaker or even absent. CONCLUSIONS: These findings suggest that
      in patients with MHE, the loss of the relationship between P300 parameters and
      RTs is related to both higher IIV of RTs and psychomotor slowing. SIGNIFICANCE:
      This study highlights the utility of investigating the relationship between
      single-trial ERPs parameters along with RT distributions to explore brain
      functioning in normal or pathological conditions.

PMID- 24035205
TI  - Prevalence of adjacent segment disc degeneration in patients undergoing anterior
      cervical discectomy and fusion based on pre-operative MRI findings.
AB  - Anterior cervical discectomy and fusion (ACDF) is a widely accepted surgical
      treatment for symptomatic cervical spondylosis. Some patients develop symptomatic
      adjacent segment degeneration, occasionally requiring further treatment. The
      cause and prevalence of adjacent segment degeneration and disease is unclear at
      present. Proponents for motion preserving surgery such as disc arthroplasty argue
      that this technique may decrease the "strain" on adjacent discs and thus decrease
      the incidence of symptomatic adjacent segment degeneration. The purpose of this
      study was to assess the pre-operative prevalence of adjacent segment degeneration
      in patients undergoing ACDF. A database review of three surgeons' practice was
      carried out to identify patients who had undergone a one- or two-level ACDF for
      degenerative disc disease. Patients were excluded if they were operated on for
      recent trauma, had an inflammatory arthropathy (for example, rheumatoid
      arthritis), or had previous spine surgery. The pre-operative MRI of each patient
      was reviewed and graded using a standardised methodology. One hundred and six
      patient MRI studies were reviewed. All patients showed some evidence of
      intervertebral disc degeneration adjacent to the planned operative segment(s).
      Increased severity of disc degeneration was associated with increased age and
      operative level, but was not associated with sagittal alignment. Disc
      degeneration was more common at levels adjacent to the surgical level than at non
      adjacent segments, and was more severe at the superior adjacent level compared
      with the inferior adjacent level. These findings support the theory that adjacent
      segment degeneration following ACDF is due in part to the natural history of
      cervical spondylosis. 

PMID- 24035206
TI  - External validation of the ability of the DRAGON score to predict outcome after
      thrombolysis treatment.
AB  - Easy-to-perform and valid assessment scales for the effect of thrombolysis are
      essential in hyperacute stroke settings. Because of this we performed an external
      validation of the DRAGON scale proposed by Strbian et al. in a Danish cohort. All
      patients treated with intravenous recombinant plasminogen activator between 2009
      and 2011 were included. Upon admission all patients underwent physical and
      neurological examination using the National Institutes of Health Stroke Scale
      along with non-contrast CT scans and CT angiography. Patients were followed up
      through the Outpatient Clinic and their modified Rankin Scale (mRS) was assessed
      after 3 months. Three hundred and three patients were included in the analysis.
      The DRAGON scale proved to have a good discriminative ability for predicting
      highly unfavourable outcome (mRS 5-6) (area under the curve-receiver operating
      characteristic [AUC-ROC]: 0.89; 95% confidence interval [CI] 0.81-0.96; p<0.001)
      and good outcome (mRS 0-2) (AUC-ROC: 0.79; 95% CI 0.73-0.85; p<0.001). When only
      patients with M1 occlusions were selected the DRAGON scale provided good
      discriminative capability (AUC-ROC: 0.89; 95% CI 0.78-1.0; p=0.003) for highly
      unfavourable outcome. We confirmed the validity of the DRAGON scale in predicting
      outcome after thrombolysis treatment.

PMID- 24035207
TI  - The feature of preventable adverse events in hospitals in the State of Rio de
      Janeiro, Brazil.
AB  - OBJECTIVE: To analyze the features of preventable adverse events (AEs) in
      hospitals inpatient in the State of Rio de Janeiro, in Brazil, in order to
      identify elements that serve as a substrate for priority actions aimed at
      improving patient safety. METHODS: Analysis of data from a baseline retrospective
      cohort study to assess the incidence of AEs in a sample of records in three
      teaching hospitals in the State of Rio de Janeiro to describe the features of
      preventable AEs. RESULTS: In a sample of 1,103 patients, were identified 65
      preventable AEs of 56 patients who suffered preventable AEs. The healthcare
      associated infections (HAI) accounted for 24.6% of preventable AEs; surgical
      complications and/or anesthetic, 20.0%; damages arising from delay or failure in
      diagnosis and/or treatment, 18.4%, pressure ulcers, 18.4%; damage from
      complications of venipuncture, 7.7%; damage due to falls, 6.2%; damage as a
      result of the use of drugs, 4.6%. The preventable AEs were responsible for
      additional 373 days of hospital stay. CONCLUSION: The HAI is the major
      preventable AEs, as observed in other developing countries. Despite the
      limitations of the study, the characterization of preventable AEs indicates that
      known and effective actions available to reduce HAI, such as hand hygiene, to
      prevent pressure ulcers, to encourage adherence to protocol and clinical
      guidelines and to create continuing education programs for health professionals,
      should compose the list of priorities of hospital managers and health
      professionals involved in the care of hospitalized patients.

PMID- 24035208
TI  - Does the walking task matter? Influence of different walking conditions on dual
      task performances in young and older persons.
AB  - Previous literature suggests that age-related deficits of dual-task walking are
      particularly pronounced with second tasks that require continuous visual
      processing. Here we evaluate whether the difficulty of the walking task matters
      as well. To this end, participants were asked to walk along a straight pathway of
      20m length in four different walking conditions: (a) wide path and preferred
      pace; (b) narrow path and preferred pace, (c) wide path and fast pace, (d)
      obstacled wide path and preferred pace. Each condition was performed concurrently
      with a task requiring visual processing or fine motor control, and all tasks were
      also performed alone which allowed us to calculate the dual-task costs (DTC).
      Results showed that the age-related increase of DTC is substantially larger with
      the visually demanding than with the motor-demanding task, more so when walking
      on a narrow or obstacled path. We attribute these observations to the fact that
      visual scanning of the environment becomes more crucial when walking in difficult
      terrains: the higher visual demand of those conditions accentuates the age
      related deficits in coordinating them with a visual non-walking task. 

PMID- 24035209
TI  - Atypical hand-foot-and-mouth disease associated with coxsackievirus A6 infection.
AB  - BACKGROUND: Hand-foot-and-mouth disease (HFMD) is an acute viral illness commonly
      caused by coxsackievirus (CV)-A16 and enterovirus 71 infections. Recently,
      atypical HFMD has been reported in association with CV-A6, an uncommon
      enterovirus strain. OBJECTIVE: We sought to describe the clinical features of
      atypical HFMD associated with CV-A6 infection and its diagnostic laboratory
      evaluation. METHODS: Patients presenting to our institution with history and
      examination suggestive of atypical HFMD from January 2012 to July 2012 were
      identified. Morphology and distribution of mucocutaneous lesions were recorded.
      Enterovirus infection was assessed by reverse transcriptase polymerase chain
      reaction of biologic specimens. Enterovirus type was determined by viral capsid
      protein 1 gene sequencing. RESULTS: Two adults and 3 children with atypical HFMD
      were identified. Four of 5 patients exhibited widespread cutaneous lesions. In 2
      patients with a history of atopic dermatitis, accentuation in areas of dermatitis
      was noted. Associated systemic symptoms prompted 4 of 5 patients to seek
      emergency care, and both adults were hospitalized for diagnostic evaluation.
      Infection with CV-A6 was confirmed in all patients. LIMITATIONS: This study is a
      case series from a single institution. CONCLUSION: Consideration of the expanded
      range of cutaneous findings in atypical HFMD caused by CV-A6 infection may assist
      clinicians in diagnosis and management.

PMID- 24035210
TI  - Elastin staining patterns in primary cicatricial alopecia.
AB  - BACKGROUND: Most biopsy specimens of cicatricial (scarring) alopecia can be
      readily subclassified as lymphocytic versus neutrophilic, but specific diagnosis
      remains difficult, particularly when a late stage of the disease is sampled.
      OBJECTIVE: We sought to document patterns of scarring highlighted by elastic
      tissue staining in primary cicatricial alopecia. METHODS: We documented Verhoeff
      elastic van Gieson staining patterns in 58 routinely embedded (vertical) biopsy
      specimens of cicatricial alopecia. Patterns of fibrosis included perifollicular
      (wedge-shaped vs broad tree trunk-shaped) and diffuse. The patterns were compared
      against the diagnosis obtained by independent expert clinical review, including
      central centrifugal cicatricial alopecia (CCCA), lichen planopilaris, traction
      alopecia, frontal fibrosing alopecia, discoid lupus erythematosus, and tufted
      folliculitis. RESULTS: Wedge-shaped perifollicular fibrosis was seen in lichen
      planopilaris but also in CCCA. Broad tree trunk-shaped perifollicular fibrosis
      was most commonly encountered in CCCA. LIMITATIONS: The retrospective nature of
      the study precluded temporal staging of the disease process. CONCLUSIONS:
      Patterns of fibrosis highlighted by elastin staining in primary cicatricial
      alopecia appear to be disease specific. Superficial wedge-shaped perifollicular
      fibrosis is associated with but may not be specific for lichen planopilaris.
      Broad tree trunk-like perifollicular fibrosis is specific for CCCA but not
      present in many cases. Elastin staining represents a useful ancillary study for
      the evaluation of late-stage scarring alopecia in routinely oriented punch biopsy
      specimens.

PMID- 24035211
TI  - Randomized controlled pilot trial of nifedipine as oral therapy vs. topical
      application in the treatment of fissure-in-ano.
AB  - BACKGROUND: Fissure-in-ano is a common condition that leads to pain and affects
      quality of life. Sphincterotomy remains the gold standard, but it may lead to
      troublesome incontinence in some patients. To overcome this problem, numerous
      pharmacologic therapies have been tested with varying outcomes. The investigators
      compared the effect of the addition of oral and topical nifedipine to
      conservative measures in the treatment of patients with fissure-in-ano. METHODS:
      Ninety patients with fissure-in-ano, randomized into 3 groups of 30 each, were
      included in the study. Group I received conventional treatment, group II received
      oral nifedipine and conventional treatment, and group III received topical
      nifedipine along with conventional treatment. Patients were followed for 8 weeks
      for pain relief (assessed using a visual analogue scale) and healing to evaluate
      the effect of treatment. RESULTS: Pain relief was significantly better in the
      group III at 3 weeks and 2 months compared with group I (P < .05). Groups II and
      III were comparable in terms of pain relief. Healing rates were significantly
      better in group II (P = .03) and group III (P = .00) compared with group I, but
      groups II and III were found to be comparable. Adverse effects were most commonly
      reported by group II patients, but these were not significantly higher than in
      other 2 groups. CONCLUSIONS: We recommend the addition of either oral or topical
      nifedipine to conservative measures to significantly improve pain relief and
      healing rates in patients with fissure-in-ano.

PMID- 24035212
TI  - Rural and urban disparities in the evolution of sentinel lymph node utilization
      in breast cancer.
AB  - BACKGROUND: Sentinel lymph node biopsy (SLNB) has become the preferred method for
      axillary nodal staging. The authors examined SLNB utilization in urban versus
      rural settings as this procedure was adopted and hypothesized that SLNB rates
      among urban populations increased faster, while the technology shift and
      acceptance of SLNB were slower at rural centers. METHODS: The Surveillance,
      Epidemiology and End Results database was used to identify patients with invasive
      node-negative ductal or lobular breast cancer diagnosed from 1998 to 2008.
      Exclusion criteria were distant metastatic disease, T4 tumors, or incomplete
      data. Residential setting was divided into groups on the basis of population
      density. RESULTS: The overall rate of SLNB increased with time (from 10% in 1998
      to 73% in 2008). The adoption of SLNB was slower in rural settings than among
      urban populations (P < .001). By 2003, only urban areas were using SLNB in >50%
      of cases. Overall, there was a 2-year lag between the increases in SLNB
      utilization rates in these groups. There was a significant difference in SLNB
      rates according to tumor size. CONCLUSION: The overall rate of SLNB remained near
      50% and was lower in rural locations in 2004. By 2008, the SLNB rate for T1 and
      T2 tumors had increased to >50% in all population categories. SLNB utilization
      was lower in all population categories as tumor size increased. There was an
      overall 2-year lag in the adoption of SLNB in less populated areas. Although this
      may represent a more conservative approach, the difference may be attributable to
      a shortage of experienced surgeons, lack of training, or lack of technological
      support at smaller institutions.

PMID- 24035213
TI  - Handoffs in general surgery residency, an observation of intern and senior
      residents.
AB  - BACKGROUND: Handoffs have become an area of concern as duty-hour restrictions
      impose an increasing number of shift changes. The objective of this study was to
      study handoffs in a general surgery residency and identify problems that exist in
      the current handoff process in preparation for a standardized implemented
      protocol. METHODS: A resident researcher observed resident-to-resident handoffs
      for 5 surgical service teams, Monday through Friday, for the middle 2 weeks of
      the 3rd month of the academic year. Each handoff was observed for the presence,
      absence, or inconsistency of code status; anticipated problems; active problems;
      current baseline status; pending tests or consults; and closed-loop
      communication. RESULTS: Thirty-eight residents in 2010 were observed, with a
      total of 52 handoffs ranging from 1 to 27 minutes in length. Five handoffs (10%)
      were by phone, 47 handoffs (90%) were observed in person, 10 handoffs (19%) were
      by senior residents, and 37 handoffs (71%) were performed by junior residents. Of
      the 47 in-person handoffs, code status was mentioned in 2 (4%), and 6 (12%) were
      given written notes. Of the 37 intern handoffs, the presence of measured criteria
      occurred in the following percentages: 59% for anticipated problems, 70% for
      active problems, 51% for current baseline status, 64% for pending tests or
      consults, and 81% for closed-loop communication. Of the 10 senior-level handoffs
      observed, all consistently included the previously mentioned criteria.
      CONCLUSIONS: This study demonstrates the lack of consistency and propensity for
      error in unstructured handoffs among junior residents. The finding that senior
      level residents exhibited consistently proficient handoffs demonstrates that
      handoffs are a learned skill. Therefore, teaching junior residents a structured
      handoff supervised by senior residents would most likely reduce the inconsistency
      and error-prone nature of the junior-level handoffs observed in our study.

PMID- 24035214
TI  - Trends in validity of central line-associated bloodstream infection surveillance
      data, New York State, 2007-2010.
AB  - BACKGROUND: In 2007, New York State (NYS) hospitals began mandatory public
      reporting of central line-associated bloodstream infection (CLABSI) data
      associated with intensive care units (ICUs) into the National Healthcare Safety
      Network (NHSN). Facilities were required to use the NHSN device-associated CLABSI
      criteria to identify laboratory-confirmed bloodstream infections. METHODS: Onsite
      audits were conducted in ICUs by NYS hospital-acquired infection program staff
      using a standardized database. Hospitals provided ICU patient medical records
      with a positive blood culture during a selected time frame. RESULTS: Between 2007
      and 2010, an average of 79% of all reporting hospitals were audited annually. Of
      the 5,697 patients audited, 3,104 (54%) had a central line in place, and 650 of
      the patients with a central line (21%) were identified as having a CLABSI by the
      hospital-acquired infection program reviewer. Between 2007 and 2010, the
      specificity increased from 90% to 99%, whereas the sensitivity remained stable at
      approximately 71%. As a result of the audit process, the NYS 2010 CLABSI rate
      increased by 5.6%. CONCLUSIONS: A standardized audit process has helped improve
      the accuracy of CLABSI reporting. Data validation provides consistent data for
      measuring the progress of infection prevention strategies and allows for relevant
      comparison of ICU data.

PMID- 24035215
TI  - Preventing the transmission of methicillin-resistant Staphylococcus aureus at a
      tertiary care cancer center in Japan: quality improvement report.
AB  - Although methicillin-resistant Staphylococcus aureus (MRSA) is endemic in the
      majority of Japanese hospitals, national guidelines for the control and
      prevention of MRSA continue to be lacking. Also, the metrics to survey the
      incidence of MRSA transmission in health care facilities is not standardized. We
      improved MRSA control practices referring to the 2003 Society for Healthcare
      Epidemiology of America guidelines and assessed the effect of multifaceted
      interventions by quasiexperimental analysis at a tertiary hospital in Japan. 

PMID- 24035216
TI  - [Evaluation and stratification of perioperative cardiac risk: Still a long
      road!].

PMID- 24035217
TI  - [Bilateral pneumothorax, cervicofacial and mediastinal emphysema after surgical
      tracheostomy].
AB  - Tracheotomy is a surgical procedure for various indications, such as ventilator
      dependence and airway obstruction. Reported rates in the literature of
      complications of tracheostomy vary widely. We report an unusual presentation of
      serious complication after surgical tracheostomy. The correct timing of
      tracheostomy is still controversial in the literature. A 74-year-old male had
      emergency surgical tracheostomy under general anesthesia. At the end of the
      procedure, in recovery room, he developed subcutaneous emphysema of the eyes.
      There was no pneumothorax seen on chest X-ray. Bronchoscopic examination through
      the tracheostomy tube showed no evidence of damage to the posterior tracheal
      wall. Three hours later patient had difficulty breathing requiring sedation with
      respiratory assistance. X-ray of the chest at this stage showed a right
      pneumothorax and extensive subcutaneous emphysema of the chest wall. Pneumothorax
      was managed using a chest tube. Two days after, a control CT scan of the chest
      showed a left pneumothorax and pneumomediastinum. The pneumothorax was managed
      using a chest tube. Bronchoscopic examination showed no obvious lesion in the
      tracheobronchial tree. The patient was treated successfully with supportive care
      and large doses of antibiotic to prevent mediastinitis. Seven days later,
      recovery was rapid and complete and CT scan of the chest was completely normal.
      The patient was discharged from the hospital on the 13th postoperative day. This
      case illustrates that complications occurring after surgical tracheostomy could
      be dramatic. Management of tracheotomy is important to prevent complications.
      There is still debate on optimal timing of tracheotomy. The last three trials
      have shown no interest to perform an early tracheotomy, neither in terms of vital
      prognosis nor in terms of the duration of mechanical ventilation. 

PMID- 24035218
TI  - Case-finding for coeliac disease in secondary care: a prospective multicentre UK
      study.
AB  - BACKGROUND: Coeliac disease affects 1% of the population. Despite this high
      prevalence, the majority of individuals are undetected. Many patients present
      with subtle symptoms which may also contribute to under diagnosis. Our aim was to
      determine the relative importance of different presenting characteristics.
      METHODS: Unselected gastroenterology patients referred to 4 hospitals in South
      Yorkshire were investigated for coeliac disease. Diagnosis was based on positive
      serology and the presence of villous atrophy. Odds ratios were calculated for
      presenting characteristics and multivariate analysis performed to identify
      independent risk factors. RESULTS: 4089 patients were assessed (41.5% male, mean
      age 55.8 +/- 18.2 years); 129 had coeliac disease (3.2%, 95% CI 2.6-3.7%).
      Multivariate analysis of patients referred to secondary care showed family
      history of coeliac disease (OR 1.26, p < 0.0001), anaemia (OR 1.03, p < 0.0001)
      and osteoporosis (OR 1.1, p = 0.006) were independent risk factors for diagnosis
      of coeliac disease. When compared to population controls, diarrhoea (OR 4.1, p <
      0.0001), weight loss (OR 2.7, p = 0.02), irritable bowel syndrome symptoms (OR
      3.2, p = 0.005) thyroid disease (OR 4.4, p = 0.01) and diabetes (OR 3.0, p =
      0.05) were also associated with increased coeliac disease risk. CONCLUSIONS:
      Coeliac disease accounts for 1 in 31 referrals in secondary care to unselected
      gastroenterology clinics. A low threshold for coeliac disease testing should be
      adopted.

PMID- 24035221
TI  - Loosening the grip of meningococcal disease in Africa.

PMID- 24035220
TI  - Effect of a serogroup A meningococcal conjugate vaccine (PsA-TT) on serogroup A
      meningococcal meningitis and carriage in Chad: a community study [corrected].
AB  - BACKGROUND: A serogroup A meningococcal polysaccharide-tetanus toxoid conjugate
      vaccine (PsA-TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by
      WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now
      being deployed across the African meningitis belt. We studied the effect of PsA
      TT on meningococcal meningitis and carriage in Chad during a serogroup A
      meningococcal meningitis epidemic. METHODS: We obtained data for the incidence of
      meningitis before and after vaccination from national records between January,
      2009, and June, 2012. In 2012, surveillance was enhanced in regions where
      vaccination with PsA-TT had been undertaken in 2011, and in one district where a
      reactive vaccination campaign in response to an outbreak of meningitis was
      undertaken. Meningococcal carriage was studied in an age-stratified sample of
      residents aged 1-29 years of a rural area roughly 13-15 and 2-4 months before and
      4-6 months after vaccination. Meningococci obtained from cerebrospinal fluid or
      oropharyngeal swabs were characterised by conventional microbiological and
      molecular methods. FINDINGS: Roughly 1.8 million individuals aged 1-29 years
      received one dose of PsA-TT during a vaccination campaign in three regions of
      Chad in and around the capital N'Djamena during 10 days in December, 2011. The
      incidence of meningitis during the 2012 meningitis season in these three regions
      was 2.48 per 100,000 (57 cases in the 2.3 million population), whereas in regions
      without mass vaccination, incidence was 43.8 per 100,000 (3809 cases per 8.7
      million population), a 94% difference in crude incidence (p<0.0001), and an
      incidence rate ratio of 0.096 (95% CI 0.046-0.198). Despite enhanced
      surveillance, no case of serogroup A meningococcal meningitis was reported in the
      three vaccinated regions. 32 serogroup A carriers were identified in 4278 age
      stratified individuals (0.75%) living in a rural area near the capital 2-4 months
      before vaccination, whereas only one serogroup A meningococcus was isolated in
      5001 people living in the same community 4-6 months after vaccination (adjusted
      odds ratio 0.019, 95% CI 0.002-0.138; p<0.0001). INTERPRETATION: PSA-TT was
      highly effective at prevention of serogroup A invasive meningococcal disease and
      carriage in Chad. How long this protection will persist needs to be established.
      FUNDING: The Bill & Melinda Gates Foundation, the Wellcome Trust, and Medecins
      Sans Fronteres.

PMID- 24035222
TI  - Strategies to retain rural breast cancer survivors in longitudinal research.
AB  - AIMS: To describe the retention of rural women in the Rural Breast Cancer
      Survivors (RBCS) Intervention. BACKGROUND: Few studies describe strategies and
      procedures for retention of participants enrolled in cancer research. Fewer
      studies focus on underserved rural cancer survivors. METHODS: A descriptive
      design was used. A conceptual model of retention based on three factors:
      researcher, participant, and context with primary, secondary, and tertiary
      strategies was used to unify the data. RESULTS: 432 women enrolled in the RBCS
      study, of which 332 (77%) were retained and completed the 12 month study.
      Favorable retention strategies included: run-in period, persistent attempts to re
      contact hard to reach, recruitment and enrollment tracking database, and a
      trusting and supportive relationship with the research nurse. CONCLUSION: A
      conceptual model of retention with differential strategies can maintain
      participant retention in a longitudinal research study.

PMID- 24035223
TI  - Antidyslipidemic and antioxidant activity of an unusual amino acid (2-amino-5
      hydroxyhexanoic acid) isolated from the seeds of Crotalaria juncea.
AB  - In continuation of our drug discovery programme on Indian medicinal plants, we
      isolated an unusual amino acid, i.e. 2-amino-5-hydroxyhexanoic acid (1) from the
      seeds of Crotalaria juncea. The 2-amino-5-hydroxyhexanoic acid (1) showed dose
      dependent lipid lowering activity in the in vivo experiments and also showed good
      in vitro antioxidant activity. The cyclized compound, 3-amino-6-methyltetrahydro
      2H-pyran-2-one (2) showed better lipid lowering and antioxidant profile than the
      parent compound 1. 

PMID- 24035224
TI  - Sauchinone from Saururus chinensis protects vascular inflammation by heme
      oxygenase-1 induction in human umbilical vein endothelial cells.
AB  - Sauchinone, a diastereomeric lignan isolated from the roots of Saururus chinensis
      (LOUR.) BAILL. (Saururaceae), is reported to exert a variety of biological
      activities such as hepatoprotective, anti-inflammatory actions and inhibitory
      effects on bone resorption. In this study, we investigated the effect of
      sauchinone in suppressing cell adhesion molecules such as vascular cell adhesion
      molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) expression in
      high glucose stimulated human umbilical vein endothelial cells (HUVEC).
      Sauchinone inhibited the phosphorylation and degradation of IkappaB-alpha, as
      well as the nuclear translocation of nuclear factor kappa B (NF-kappaB) p65
      caused by the stimulation of high glucose. In addition, sauchinone induced heme
      oxygenase (HO)-1 expression through nuclear translocation of nuclear factor E2
      related factor 2 in HUVEC. The effects of sauchinone on the high glucose-induced
      expression of VCAM-1 and ICAM-1 and nuclear translocation of NF-kappaB p65 were
      partially reversed by transfection of the cells with HO-1 siRNA. These findings
      suggest that sauchinone-induced HO-1 expression plays a key role in the vascular
      protective effects of sauchinone in HUVEC. 

PMID- 24035225
TI  - Effect of chito-oligosaccharide on the oral absorptions of phenolic acids of Flos
      Lonicerae extract.
AB  - Phenolic acids, the main active ingredients in Flos Lonicerae extract possess
      strong antibacterial, antioxidant and antiviral effects, and their contents was
      higher largely than that of other ingredients such as flavones, but the absolute
      bioavailability orally was significantly low, which is significant low
      influencing clinical efficacies of its oral preparations. In the present study,
      in vitro Caco-2 cell, in situ single-pass intestinal perfusion and in vivo
      pharmacokinetics study were performed to investigate the effects of COS on the
      intestinal absorption of phenolic acids. The pharmacological effects such as
      antiviral activity improvement by COS were verified by MDCK cell damage
      inhibition rate after influenza virus propagation. The observations from in vitro
      Caco-2 cell showed that the absorption of phenolic acids in Flos Lonicerae
      extract could be improved by COS. Meanwhile, COS at the same low, medium and high
      concentrations caused a significant, concentration-dependent increase in the Papp
      value for phenolic acids compared to the control group (p<0.05), and was all safe
      for the Caco-2 cells. The observations from single-pass intestinal perfusion in
      situ model showed that the intestinal absorption of phenolic acids can be
      enhanced by COS. Meanwhile, the absorption enhancing effect of phenolic acids
      might be saturable in different intestine sites. In pharmacokinetics study, COS
      at dosage of 25 mg/kg improved the bioavailability of phenolic acids in Flos
      Lonicerae extract to the greatest extent, and was safe for gastrointestine from
      morphological observation. Besides, treatment with Flos Lonicerae extract with
      COS at dosage of 25 mg/kg prevented MDCK cell damage upon influenza virus
      propagation better than that of control. All findings above suggested that COS at
      dosage of 25 mg/kg might be safe and effective absorption enhancer for improving
      the bioavailability of phenolic acids and the antiviral activity in vitro in Flos
      Lonicerae extract.

PMID- 24035226
TI  - Protection of H9c2 rat cardiomyoblasts against oxidative insults by total paeony
      glucosides from Radix Paeoniae Rubrae.
AB  - Total paeony glucosides (TPG) extracted from the roots of Radix Paeoniae Rubrae,
      have been approved for the therapy of rheumatoid arthritis by the State Food and
      Drug Administration. We previously demonstrated the myocardial protective effects
      of TPG in both isoprenaline-induced myocardial ischemia rat and acute myocardial
      infarction rat. However, the underlying mechanism of TPG effect in cardiomyocytes
      remains to be investigated. The aims of this study were to elucidate the effect
      of TPG on the activities of antioxidant defense targets and the bioenergetic
      system in rat cardiomyocytes. The changes of viability, antioxidant defense
      system activities, protein contents, and mitochondrial functions in tert-butyl
      hydroperoxide challenged H9c2 rat cardiomyoblasts were evaluated. The results
      suggest that TPG ameliorated cardiomyoblast dysfunction by preserving antioxidant
      defense and bioenergetic system. 

PMID- 24035227
TI  - beta-Lapachone activity in synergy with conventional antimicrobials against
      methicillin resistant Staphylococcus aureus strains.
AB  - The aim of this study was to evaluate the antimicrobial activity of lapachol,
      alpha-lapachone, beta-lapachone and six antimicrobials (ampicillin,
      amoxicillin/clavulanic acid, cefoxitin, gentamicin, ciprofloxacin and meropenem)
      against twelve strains of Staphylococcus aureus from which resistance phenotypes
      were previously determined by the disk diffusion method. Five S. aureus strains
      (LFBM 01, LFBM 26, LFBM 28, LFBM 31 and LFBM 33) showed resistance to all
      antimicrobial agents tested and were selected for the study of the interaction
      between beta-lapachone and antimicrobial agents, busing checkerboard method. The
      criteria used to evaluate the synergistic activity were defined by the Fractional
      Inhibitory Concentration Index (FICI). Among the naphthoquinones, beta-lapachone
      was the most effective against S. aureus strains. FICI values ranged from 0.07 to
      0.5, suggesting a synergistic interaction against multidrug resistant S. aureus
      (MRSA) strains. An additive effect was observed with the combination beta
      lapachone/ciprofloxacin against the LFBM 33 strain. The combination of beta
      lapachone with cefoxitin showed no added benefit against LFBM 31 and LFBM 33
      strains. This study demonstrated that, in general, beta-lapachone combined with
      beta lactams antimicrobials, fluoroquinolones and carbapenems acts
      synergistically inhibiting MRSA strains. 

PMID- 24035228
TI  - The art and science of publishing: reflections from editors of surgery journals.
AB  - During the 8th Annual Academic Surgical Congress held in New Orleans, Louisiana,
      on February 5-7, 2013, the Association for Academic Surgery (AAS) Presidential
      Session was dedicated to the topic of publishing. A survey consisting of 37
      questions on issues related to publishing was administered to the AAS membership
      1 mo before the meeting. The results of the survey were then presented during the
      2013 AAS Presidential Session. In addition, a panel of five editors from surgery
      journals relevant to the membership of the AAS was convened to discuss topics
      addressed in the results of the survey. These topics included: (1) how to publish
      in high-impact factor journals; (2) top five reasons why manuscripts get
      rejected; (3) the do's and don'ts of publishing (i.e., ethics of publishing); (4)
      how to get on an editorial board; and (5) the future of publishing. This review
      summarizes the contents of this AAS Presidential Session and provides information
      relevant for any academician, investigator, or scientist.

PMID- 24035229
TI  - Effect of collagen and elastin content on the burst pressure of human blood
      vessel seals formed with a bipolar tissue sealing system.
AB  - BACKGROUND: Bipolar devices are routinely used to seal blood vessels instead of
      sutures and clips. Recent work examining the impact of vascular proteins on
      bipolar seal performance found that collagen and elastin (CE) content within
      porcine arteries was a significant predictor of a vessel's burst pressure (VBPr).
      This study examined seal performance across a range of human blood vessels to
      investigate whether a similar relationship existed. In addition, we compared VBPr
      and CE content between porcine and human blood vessels. Our primary hypothesis is
      that higher collagen-to-elastin ratio will predict higher VBPr in human
      vasculature. METHODS: In six cadavers, 185 blood vessels from nine anatomic
      locations were sealed using a bipolar electrosurgical system. A linear mixed
      model framework was used to evaluate the impact of vessel diameter and CE content
      on VBPr. RESULTS: The effect of CE ratio on VBPr is modified by vessel size, with
      CE ratio having larger influence on VBPr in smaller diameter vessels. Seal burst
      pressure of vessels 2-5 mm in diameter was significantly associated with their CE
      content. Comparison of average VBPr between species revealed porcine carotid and
      iliac arteries (440-670 mmHg) to be the best vessel types for predicting the seal
      strength of most human blood vessels (420-570 mmHg) examined. CONCLUSIONS: CE
      content significantly modified the seal strength of small to medium sized blood
      vessels but had limited impact on vessels >5 mm.

PMID- 24035230
TI  - Assessing warm ischemic injury of pig livers at hypothermic machine perfusion.
AB  - BACKGROUND: Livers originating from donation after circulatory death (DCD) donors
      are exposed to warm ischemia (WI) before liver transplantation (LTx). Currently,
      there are no objective tests to evaluate the damage sustained before LTx. This
      study aims to identify surrogate markers for liver injury that can be assessed
      during hypothermic machine perfusion (HMP) preservation. In addition, we want to
      use mathematical equation modeling combining these markers to improve our
      assessment of DCD livers for transplantation. MATERIALS AND METHODS: Porcine
      livers were exposed to incremental periods of WI (0-120 min) and subsequently HMP
      preserved for 4 h. Biochemical and hemodynamic parameters were repeatedly
      measured in the perfusate during HMP. Subsequently, to mimic LTx, normothermic
      isolated-liver perfusion was applied for 2 h and the injury assessed using a
      morphological score. RESULTS: With increasing WI periods, the perfusate became
      more acidotic, and levels of aspartate aminotransferase (AST), liver fatty acid
      binding protein, redox-active iron, and arterial vascular resistance increased. A
      damage index, combining AST and pH (damage index = 2 - 37 * beta(AST) - 257 *
      beta(pH)) based on multifactorial analysis of the changing pattern of these
      markers, had increased sensitivity and specificity to reflect WI and reperfusion
      injury. CONCLUSIONS: This proof of concept study demonstrated the potential role
      for objective evaluation of DCD porcine livers during HMP and the advantage to
      use multifactorial analysis on the markers' changing pattern.

PMID- 24035231
TI  - The dose-effect relationship in extracorporeal shock wave therapy: the optimal
      parameter for extracorporeal shock wave therapy.
AB  - BACKGROUND: Extracorporeal shock wave therapy (ESWT) has been demonstrated to
      have the angiogenic effect on ischemic tissue. We hypothesize that ESWT exerts
      the proangiogenesis effect with an energy density-dependent mode on the target
      cells. MATERIALS AND METHODS: Endothelial progenitor cells (EPCs) of rats were
      obtained by cultivation of bone marrow-derived mononuclear cells. EPCs were
      divided into five groups of different energy densities, and each group was
      furthermore subdivided into four groups of different shock numbers. Thus, there
      were 20 subgroups in total. The expressions of angiogenic factors, apoptotic
      factors, inflammation mediators, and chemotactic factors were examined, and the
      proliferation activity was measured after ESWT. RESULTS: When EPCs were treated
      with low-energy (0.04-0.13 mJ/mm(2)) shock wave, the expressions of endothelial
      nitric oxide synthase, angiopoietin (Ang) 1, Ang-2, and B-cell lymphoma 2
      increased and those of interleukin 6, fibroblast growth factor 2, C-X-C chemokine
      receptor type 4, vascular endothelial growth factor a, Bcl-2-associated X
      protein, and caspase 3 decreased. stromal cell-derived factor 1 changed without
      statistical significance. When cells were treated with high-energy (0.16
      mJ/mm(2)) shock wave, most of the expressions of cytokines declined except the
      apoptotic factors and fibroblast growth factor 2, and cells lead to apoptosis.
      The proliferation activity and the ratio of Ang-1/Ang-2 reached their peak
      values, when cells were treated with ESWT with the intensity ranging from 0.10
      0.13 mJ/mm(2) and shock number ranging from 200-300 impulses. Meanwhile, a
      minimal value of the ratio of Bax/Bcl-2 was observed. CONCLUSIONS: There is a
      dose-effect relationship in ESWT. The shock intensity ranging from 0.10-0.13
      mJ/mm(2) and shock number ranging from 200-300 impulses were the optimal
      parameters for ESWT to treat cells in vitro.

PMID- 24035232
TI  - Lipophilic amino alcohols reduces carrageenan-induced paw edema and anti-OVA DTH
      in BALB/c mice.
AB  - The inflammation process is a coordinated response of the organism related to
      immune response with release of pro-inflammatory substances, as nitric oxide, TNF
      alpha and IL-1beta. In this work, a series of lipophilic amino alcohols were
      evaluated on RAW264.7 and primary macrophages for the modulation of nitric oxide
      and TNF-alpha. The most potent compounds were submitted to the treatment of
      BALB/c mice and evaluation of the carrageenan-induced paw edema and TNF-alpha and
      IL1-beta release in the paws and anti-OVA delayed type hypersensitivity reaction.
      RAW264.7 and primary macrophages were incubated in the presence of amino alcohols
      at different concentrations (1, 0.5, 0.05 and 0.005 MUg mL(-1)). All tested
      compounds were not cytotoxic, however the inhibition of NO and TNF-alpha were
      observed only in RAW264.7 cultures. The NO production were reduced in 100% for
      all compounds, but only the compounds 4a and 4b expressively reduced the TNF
      alpha release (67% and 92% respectively). On the carrageenan-induced paw edema,
      the compound 4b treatment showed reduction of edema, TNF-alpha and IL-1beta as
      efficient as dexamethasone treatment. Meanwhile, the compound 4a treatment showed
      only slight reduction of paw edema. In the anti-OVA DTH reaction, both compounds
      showed reduction in the paw edema as effective as dexamethasone. In function of
      the observed results in vitro and in the acute and anti-OVA inflammation of mice
      paw edema compound 4b showed promissory anti-inflammatory properties.

PMID- 24035233
TI  - Facile immunostaining and labeling of nonadherent cells using a microfluidic
      device to entrap the cells.
AB  - We fabricated a microfluidic device for the entrapment of nonadherent cells.
      Solution exchange was easily performed by introducing the solution into the cell
      trapping microchannel. Immunostaining and labeling of the cell membrane of THP-1
      cells were demonstrated using this device, which does not require cumbersome
      repetition of centrifugation and resuspension steps.

PMID- 24035234
TI  - Molecular mechanisms involved in convergent crop domestication.
AB  - Domestication has helped to understand evolution. We argue that, vice versa,
      novel insights into evolutionary principles could provide deeper insights into
      domestication. Molecular analyses have demonstrated that convergent phenotypic
      evolution is often based on molecular changes in orthologous genes or pathways.
      Recent studies have revealed that during plant domestication the causal mutations
      for convergent changes in key traits are likely to be located in particular
      genes. These insights may contribute to defining candidate genes for genetic
      improvement during the domestication of new plant species. Such efforts may help
      to increase the range of arable crops available, thus increasing crop
      biodiversity and food security to help meet the predicted demands of the
      continually growing global population under rapidly changing environmental
      conditions. 

PMID- 24035235
TI  - Localised ABA signalling mediates root growth plasticity.
AB  - Two recent reports show that cellular abscisic acid (ABA) signalling, together
      with other phytohormone signalling pathways, is crucial for salt-regulated root
      growth dynamics. Here we discuss these findings and place them in a broader
      framework on how cellular hormone signalling regulates root growth plasticity in
      response to environmental cues. 

PMID- 24035236
TI  - Transition from glycogen to starch metabolism in Archaeplastida.
AB  - In this opinion article we propose a scenario detailing how two crucial
      components have evolved simultaneously to ensure the transition of glycogen to
      starch in the cytosol of the Archaeplastida last common ancestor: (i) the
      recruitment of an enzyme from intracellular Chlamydiae pathogens to facilitate
      crystallization of alpha-glucan chains; and (ii) the evolution of novel types of
      polysaccharide (de)phosphorylating enzymes from preexisting glycogen
      (de)phosphorylation host pathways to allow the turnover of such crystals. We
      speculate that the transition to starch benefitted Archaeplastida in three ways:
      more carbon could be packed into osmotically inert material; the host could
      resume control of carbon assimilation from the chlamydial pathogen that triggered
      plastid endosymbiosis; and cyanobacterial photosynthate export could be
      integrated in the emerging Archaeplastida. 

PMID- 24035237
TI  - Dietary fibre intake associated with reduced risk of oesophageal cancer in
      Xinjiang, China.
AB  - OBJECTIVE: To ascertain the relationship between dietary fibre intake and risk of
      oesophageal cancer in remote northwest China, where the cancer incidence is known
      to be high. METHODS: A case-control study was conducted during 2008-2009 in the
      Urumqi and Shihezi, Xinjiang Uyghur Autonomous Region of China. Participants were
      359 incident oesophageal cancer patients and 380 hospital-based controls.
      Information on habitual foods consumption was obtained by face-to-face interview,
      from which dietary fibre intakes were estimated using the Chinese food
      composition tables. RESULTS: The oesophageal cancer patients reported lower
      intake levels of total dietary fibre and fibre derived from vegetables and fruits
      than those of controls. Overall, regular intake of fibre was inversely associated
      with the oesophageal cancer risk, the adjusted odds ratio being 0.47 (95%
      confidence interval 0.32-0.69) for the highest (>27 g) versus the lowest (<16 g)
      tertile of daily intake, with a significant dose-response relationship (p=0.004).
      Similar reductions in risk were also apparent for high intake levels of vegetable
      fibre and fruit fibre, but to a lesser extent for cereal fibre. CONCLUSION:
      Habitual intake of dietary fibre was associated with a reduced risk of
      oesophageal cancer for adults in northwest China.

PMID- 24035238
TI  - Racial differences in nasopharyngeal carcinoma in the United States.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant neoplasm arising from
      the mucosal epithelium of the nasopharynx. Different races can have different
      etiology, presentation, and progression patterns. METHODS: Data were analyzed on
      NPC patients in the United States reported to the SEER (Surveillance,
      Epidemiology, and End Results) database between 1973 and 2009. Racial groups
      studied included non-Hispanic whites, Hispanic whites, blacks, Asians, and
      others. Patient characteristics, age-adjusted incidence and mortality rates,
      treatment, and five-year relative survival rates were compared across races.
      Stratification by stage at diagnosis and histologic type was considered.
      Multivariate regression was conducted to evaluate the significance of racial
      differences. RESULTS: Patient characteristics that were significantly different
      across races included age at diagnosis, histologic type, in situ/malignant tumors
      in lifetime, stage, grade, and regional nodes positive. Incidence and mortality
      rates were significantly different across races, with Asians having the highest
      rates overall and stratified by age and/or histologic type. Asians also had the
      highest rate of receiving radiation only. The racial differences in treatment
      were significant in the multivariate stratified analysis. When stratified by
      stage and histologic type, Asians had the best five-year survival rates. The
      survival experience of other races depended on stage and type. In the
      multivariate analysis, the racial differences were significant. CONCLUSIONS:
      Analysis of the SEER data shows that racial differences exist among NPC patients
      in the U.S. This result can be informative to cancer epidemiologists and
      clinicians.

PMID- 24035239
TI  - Genetic variations in CTLA-4, TNF-alpha, and LTA and susceptibility to T-cell
      lymphoma in a Chinese population.
AB  - OBJECTIVE: T-cell lymphoma is a highly aggressive malignant lymphoma that is rare
      in Caucasians but relatively common in Asian populations. Factors regulating T
      cell proliferation and function may play an important role in the pathogenesis of
      T-cell lymphoma. METHODS: A total of 8 single nucleotide polymorphisms in
      cytotoxic T lymphocyte antigen-4 (CTLA-4), tumor necrosis factor-alpha (TNF
      alpha), and lymphotoxin-alpha (LTA) genes were detected by polymerase chain
      reaction-ligation detection reaction analysis in a Chinese population of 291
      patients with T-cell lymphoma and 300 healthy controls. Logistic regression was
      used to determine the odds ratios (ORs) and 95% confidence intervals for the
      associations of genotypes and haplotypes with T-cell lymphoma risk. RESULTS:
      Among these polymorphisms, the LTA +252AA genotype was significantly associated
      with T-cell lymphoma risk (OR, 2.3; P=0.002). Furthermore, the TNF-alpha/LTA
      haplotype C-G-G-A (TNF-alpha -857C, -308G, and -238G and LTA +252A) showed a
      significantly increased risk for T-cell lymphoma (OR, 1.6; P=0.001). CONCLUSION:
      Our study suggested that the LTA +252G>A polymorphism may influence
      susceptibility to T-cell lymphoma in the Chinese population.

PMID- 24035240
TI  - Colorectal cancer screening by guaiac faecal occult blood test in France:
      Evaluation of the programme two years after launching.
AB  - BACKGROUND: The French national screening programme for colorectal cancer (CRC)
      was rolled out nationwide from 2008. It targets men and women aged 50-74 who are
      invited every 2 years to perform a guaiac faecal occult blood test, followed, if
      positive, by a colonoscopy. This paper presents the evaluation of the programme
      for the 46 French districts that conducted a comprehensive screening campaign
      during 2008-2009, targeting 9.7 million people. METHODS: National database
      gathering information on people who were screened was used to estimate indicators
      reflecting the programme performance. RESULTS: Participation was 34.3%, with
      nearly three million people being tested. The percentage of positive tests was
      2.8%. Completion of colonoscopies following a positive test was 88%. For men,
      36.8% of the results of colonic explorations were normal, 40.1% were adenomas,
      and 9.0% were CRC, based on the most pejorative lesion. For women, corresponding
      figures were 55.9%, 25.7% and 5.8%. A CRC was detected for 7.5% of people who had
      a colonic exploration. The advanced adenoma detection rate among those screened
      was 4.90/00 and the CRC detection rate was 1.90/00. The description of CRC could
      only be made for 21 districts, for which 1441 invasive colonic adenocarcinomas
      were diagnosed; of these, 43% were stage I, 23% stage II, 25% stage III and 9%
      stage IV. CONCLUSION: This first evaluation since the programme was rolled out
      provides an inventory of CRC screening in France and points out some improvements
      expected, especially in terms of participation which is below the European
      recommendations. Future evaluations will analyse trends in these indicators.

PMID- 24035243
TI  - Waste problems and our lifestyle.

PMID- 24035244
TI  - Nitrogen availability and indirect measurements of greenhouse gas emissions from
      aerobic and anaerobic biowaste digestates applied to agricultural soils.
AB  - Recycling biowaste digestates on agricultural land diverts biodegradable waste
      from landfill disposal and represents a sustainable source of nutrients and
      organic matter (OM) to improve soil for crop production. However, the dynamics of
      nitrogen (N) release from these organic N sources must be determined to optimise
      their fertiliser value and management. This laboratory incubation experiment
      examined the effects of digestate type (aerobic and anaerobic), waste type
      (industrial, agricultural and municipal solid waste or sewage sludge) and soil
      type (sandy loam, sandy silt loam and silty clay) on N availability in digestate
      amended soils and also quantified the extent and significance of the
      immobilisation of N within the soil microbial biomass, as a possible regulatory
      mechanism of N release. The digestate types examined included: dewatered,
      anaerobically digested biosolids (DMAD); dewatered, anaerobic mesophilic
      digestate from the organic fraction of municipal solid waste (DMADMSW); liquid,
      anaerobic co-digestate of food and animal slurry (LcoMAD) and liquid,
      thermophilic aerobic digestate of food waste (LTAD). Ammonium chloride (NH4Cl)
      was included as a reference treatment for mineral N. After 48 days, the final,
      maximum net recoveries of mineral N relative to the total N (TN) addition in the
      different digestates and unamended control treatments were in the decreasing
      order: LcoMAD, 68%; LTAD, 37%, DMAD, 20%; and DMADMSW, 11%. A transient increase
      in microbial biomass N (MBN) was observed with LTAD application, indicating
      greater microbial activity in amended soil and reflecting the lower stability of
      this OM source, compared to the other, anaerobic digestate types, which showed no
      consistent effects on MBN compared to the control. Thus, the overall net release
      of digestate N in different soil types was not regulated by N transfer into the
      soil microbial biomass, but was determined primarily by digestate properties and
      the capacity of the soil type to process and turnover digestate N. In contrast to
      the sandy soil types, where nitrate (NO3-) concentrations increased during
      incubation, there was an absence of NO3- accumulation in the silty clay soil
      amended with LTAD and DMADMSW. This provided indirect evidence for
      denitrification activity and the gaseous loss of N, and the associated increased
      risk of greenhouse gas emissions under certain conditions of labile C supply
      and/or digestate physical structure in fine-textured soil types. The significance
      and influence of the interaction between soil type and digestate stability and
      physical properties on denitrification processes in digestate-amended soils
      require urgent investigation to ensure management practices are appropriate to
      minimise greenhouse gas emissions from land applied biowastes.

PMID- 24035245
TI  - Optimal planning for the sustainable utilization of municipal solid waste.
AB  - The increasing generation of municipal solid waste (MSW) is a major problem
      particularly for large urban areas with insufficient landfill capacities and
      inefficient waste management systems. Several options associated to the supply
      chain for implementing a MSW management system are available, however to
      determine the optimal solution several technical, economic, environmental and
      social aspects must be considered. Therefore, this paper proposes a mathematical
      programming model for the optimal planning of the supply chain associated to the
      MSW management system to maximize the economic benefit while accounting for
      technical and environmental issues. The optimization model simultaneously selects
      the processing technologies and their location, the distribution of wastes from
      cities as well as the distribution of products to markets. The problem was
      formulated as a multi-objective mixed-integer linear programing problem to
      maximize the profit of the supply chain and the amount of recycled wastes, where
      the results are showed through Pareto curves that tradeoff economic and
      environmental aspects. The proposed approach is applied to a case study for the
      west-central part of Mexico to consider the integration of MSW from several
      cities to yield useful products. The results show that an integrated utilization
      of MSW can provide economic, environmental and social benefits. 

PMID- 24035246
TI  - Modelling of beef sensory quality for a better prediction of palatability.
AB  - Despite efforts by the industry to control the eating quality of beef, there
      remains a high level of variability in palatability, which is one reason for
      consumer dissatisfaction. In Europe, there is still no reliable on-line tool to
      predict beef quality and deliver consistent quality beef to consumers. Beef
      quality traits depend in part on the physical and chemical properties of the
      muscles. The determination of these properties (known as muscle profiling) will
      allow for more informed decisions to be made in the selection of individual
      muscles for the production of value-added products. Therefore, scientists and
      professional partners of the ProSafeBeef project have brought together all the
      data they have accumulated over 20 years. The resulting BIF-Beef (Integrated and
      Functional Biology of Beef) data warehouse contains available data of animal
      growth, carcass composition, muscle tissue characteristics and beef quality
      traits. This database is useful to determine the most important muscle
      characteristics associated with a high tenderness, a high flavour or generally a
      high quality. Another more consumer driven modelling tool was developed in
      Australia: the Meat Standards Australia (MSA) grading scheme that predicts beef
      quality for each individual muscle*specific cooking method combination using
      various information on the corresponding animals and post-slaughter processing
      factors. This system has also the potential to detect variability in quality
      within muscles. The MSA system proved to be effective in predicting beef
      palatability not only in Australia but also in many other countries. The results
      of the work conducted in Europe within the ProSafeBeef project indicate that it
      would be possible to manage a grading system in Europe similar to the MSA system.
      The combination of the different modelling approaches (namely muscle biochemistry
      and a MSA-like meat grading system adapted to the European market) is a promising
      area of research to improve the prediction of beef quality. In both approaches,
      the volume of data available not only provides statistically sound correlations
      between various factors and beef quality traits but also a better understanding
      of the variability of beef quality according to various criteria (breed, age,
      sex, pH, marbling etc.).

PMID- 24035247
TI  - Associations of genetic and non-genetic factors with concentrations of iron and
      zinc in the longissimus muscle of lamb.
AB  - There is a concern regarding the possible decline of nutritional value of meat
      with an increasing selection for lean meat yield. The selection for reduced
      fatness reduces muscle aerobicity and possible subsequent mineral concentrations.
      Average concentrations of iron and zinc of 5625 lamb longissimus muscles were
      2.03 and 2.43 mg/100 g, qualifying as a good source claim for the majority of the
      population. Reduced post-weaning fat depth was associated with decreased
      concentrations of iron but not zinc, whereas post-weaning eye muscle depth and
      weaning weight were not associated with either mineral. These results confirm
      that the impact of lean meat yield selection on these minerals is minimal, but
      should be monitored to avoid lower levels. Both minerals had a positive
      relationship with age at slaughter, highlighting age as a key determinant of the
      concentration of these nutrients. The magnitude of the positive associations of
      isocitrate dehydrogenase and myoglobin with iron was larger than for zinc, but
      they strongly indicated the association of these aerobic makers with both
      minerals.

PMID- 24035248
TI  - Evaluation of a minimally aggressive method of patellofemoral osteoarthritis
      treatment at 10 years minimum follow-up.
AB  - BACKGROUND: Knee osteoarthritis mainly affecting the lateral facet of the
      patella, especially in young patients, is a definite challenge to the surgeon.
      Our purpose was to investigate the long-term outcome of a simple operation such
      as the partial lateral facetectomy on middle-aged to elderly patients with
      predominant lateral patellofemoral osteoarthritis. METHODS: A retrospective, long
      term study of 39 knees (28 females, mean aged at surgery 61yearsold) with a
      minimum follow-up of 10years was performed. Evaluations included preoperative and
      postoperative questionnaires, physical examinations, and radiographs. RESULTS:
      The main outcomes included the initial anterior pain relief, with higher scores
      using the Knee Society Score (that improved in 84% of the knees), and the
      eventual failure of the technique, including percentage of patients that required
      secondary total knee replacement (30% of the knees). CONCLUSION: Partial lateral
      facetectomy aiming to decrease the high pressure in the lateral facet of the
      patella confirmed frequent pain relief. This surgical procedure being minimally
      invasive, relatively simple, and effective in selected patients, is a valid early
      alternative to more complex operations and does not preclude further
      reconstructive surgery in case of disease progression.

PMID- 24035249
TI  - A nail in the head.

PMID- 24035250
TI  - Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing
      spondylitis: a randomised, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Ankylosing spondylitis is a chronic immune-mediated inflammatory
      disease characterised by spinal inflammation, progressive spinal rigidity, and
      peripheral arthritis. Interleukin 17 (IL-17) is thought to be a key inflammatory
      cytokine in the development of ankylosing spondylitis, the prototypical form of
      spondyloarthritis. We assessed the efficacy and safety of the anti-IL-17A
      monoclonal antibody secukinumab in treating patients with active ankylosing
      spondylitis. METHODS: We did a randomised double-blind proof-of-concept study at
      eight centres in Europe (four in Germany, two in the Netherlands, and two in the
      UK). Patients aged 18-65 years were randomly assigned (in a 4:1 ratio) to either
      intravenous secukinumab (2*10 mg/kg) or placebo, given 3 weeks apart.
      Randomisation was done with a computer-generated block randomisation list without
      a stratification process. The primary efficacy endpoint was the percentage of
      patients with a 20% response according to the Assessment of SpondyloArthritis
      international Society criteria for improvement (ASAS20) at week 6 (Bayesian
      analysis). Safety was assessed up to week 28. This study is registered with
      ClinicalTrials.gov, number NCT00809159. FINDINGS: 37 patients with moderate-to
      severe ankylosing spondylitis were screened, and 30 were randomly assigned to
      receive either intravenous secukinumab (n=24) or placebo (n=6). The final
      efficacy analysis included 23 patients receiving secukinumab and six patients
      receiving placebo, and the safety analysis included all 30 patients. At week 6,
      ASAS20 response estimates were 59% on secukinumab versus 24% on placebo (99.8%
      probability that secukinumab is superior to placebo). One serious adverse event
      (subcutaneous abscess caused by Staphylococcus aureus) occurred in the
      secukinumab-treated group. INTERPRETATION: Secukinumab rapidly reduced clinical
      or biological signs of active ankylosing spondylitis and was well tolerated. It
      is the first targeted therapy that we know of that is an alternative to tumour
      necrosis factor inhibition to reach its primary endpoint in a phase 2 trial.
      FUNDING: Novartis.

PMID- 24035251
TI  - 17 and 23: prime numbers for ankylosing spondylitis?

PMID- 24035252
TI  - Renewing the promise of survival for children.

PMID- 24035253
TI  - Potentiation of cytotoxicity of paclitaxel in combination with Cl-IB-MECA in
      human C32 metastatic melanoma cells: A new possible therapeutic strategy for
      melanoma.
AB  - Metastatic melanoma monotherapies with drugs such as dacarbazine, cisplatin or
      paclitaxel (PXT) are associated with significant toxicity and low efficacy rates.
      These facts reinforce the need for development of novel agents or combinatory
      strategies. Cl-IB-MECA is a small molecule, orally bioavailable, well tolerated
      and currently under clinical trials as an anticancer agent. Our aim was to
      investigate a possible combinatory therapeutic strategy using PXT and Cl-IB-MECA
      on human C32 melanoma cells and its underlying mechanisms. Cytotoxicity was
      evaluated using MTT reduction, lactate dehydrogenase leakage and neutral red
      uptake assays, for different concentrations and combinations of both agents, at
      24 and 48 h. Apoptosis was also assessed using fluorescence microscopy and
      through the evaluation of caspases 8, 9, and 3 activities. We demonstrated, for
      the first time, that combination of PXT and Cl-IB-MECA significantly increases
      cytotoxicity for clinically relevant concentrations. This combination seems to
      act synergistically in disrupting membrane integrity, but also causing lysosomal
      and mitochondrial dysfunction. When using the lowest PTX concentration (10
      ng/mL), co-incubation with CI-IB-MECA (micromolar concentrations) potentiated
      overall cytotoxic effects and morphological signs of apoptosis. All combinations
      studied enhanced caspase 8, 9, and 3 activities, suggesting the involvement of
      both intrinsic and extrinsic apoptotic pathways. The possibility that
      cytotoxicity elicited by Cl-IB-MECA, alone or in combination with PXT, involves
      adenosine receptor activation was discarded and results confirmed that oxidative
      stress is only involved in cytotoxicity after treatment with PXT, alone. Being
      melanoma a very apoptosis-resistance cancer, this combination seems to hold
      promise as a new therapeutic strategy for melanoma.

PMID- 24035254
TI  - Pontic site development with a root submergence technique for a screw-retained
      prosthesis in the anterior maxilla.
AB  - Techniques for pontic site development usually involve various hard and soft
      tissue augmentation procedures. This article describes an alternative approach to
      developing a pontic site by using a root submergence technique for a screw
      retained fixed dental prosthesis in the anterior maxilla. 

PMID- 24035255
TI  - No association between catechol-O-methyltransferase (COMT) genotype and attention
      deficit hyperactivity disorder (ADHD) in Japanese children.
AB  - OBJECTIVE: This study ascertained the association between attention
      deficit/hyperactivity disorder (ADHD) in Japanese children and a polymorphism of
      catechol-O-methyltransferase (COMT), a dopamine-control gene. The secondary aim
      of the study was the evaluation of a putative association between methylphenidate
      (MPH) effect/adverse effects and the COMT genotype. METHODS: To ascertain the
      distribution of the Val158Met variant of COMT, 50 children meeting ADHD inclusion
      criteria were compared with 32 healthy children. Clinical improvement and the
      occurrence of adverse effects were measured before and 3 months after MPH
      administration in children with ADHD, and analyzed for genotype association.
      Wechsler Intelligence Scale for Children-Third Edition (WISC-III), age, MPH dose
      were included as co-variables. RESULTS: The occurrence of the COMT Val/Val
      genotype was significantly higher in children with ADHD (chi(2)(1)=7.13, p<0.01).
      However, there was no significant difference in the Val/Val genotype according to
      disorder, and WISC and ADHD rating scale scores, after correcting for the
      interaction between disorder and COMT genotype. Furthermore, no significant
      difference in MPH effect/adverse effects was observed in association with the
      COMT genotype in the ADHD group. CONCLUSIONS: These results showed a lack of
      association between the COMT Val/Val genotype and ADHD in Japan.

PMID- 24035256
TI  - Respiratory and facial protection: a critical review of recent literature.
AB  - Infectious micro-organisms may be transmitted by a variety of routes. This is
      dependent on the particular pathogen and includes bloodborne, droplet, airborne,
      and contact transmission. Some micro-organisms are spread by more than one route.
      Respiratory and facial protection is required for those organisms which are
      usually transmitted via the droplet and/or airborne routes or when airborne
      particles have been created during 'aerosol-generating procedures'. This article
      presents a critical review of the recently published literature in this area that
      was undertaken by Health Protection Scotland and the Healthcare Infection Society
      and which informed the development of guidance on the use of respiratory and
      facial protection equipment by healthcare workers. 

PMID- 24035257
TI  - Increase in reported Clostridium difficile cases as unintended consequence of
      enhanced norovirus testing.

PMID- 24035258
TI  - [Cardiac MRI: technology, clinical applications, and future directions].
AB  - The field of cardiovascular MRI has evolved rapidly over the past decade, feeding
      new applications across a broad spectrum of clinical and research areas. Advances
      in magnet hardware technology, and key developments such as segmented k-space
      acquisitions, advanced motion encoding techniques, ultra-rapid perfusion imaging
      and delayed myocardial enhancement imaging have all contributed to a revolution
      in how patients with ischemic and non-ischemic heart disease are diagnosed and
      treated. Actually, cardiac MRI is a widely accepted method as the "gold standard"
      for detection and characterization of many forms of cardiac diseases. The aim of
      this review is to present an overview of cardiac MRI technology, advances in
      clinical applications, and future directions. 

PMID- 24035259
TI  - [Arteriovenous malformation of the left upper limb in stage II of Schobinger: A
      case report in Madagascar].
AB  - Arteriovenous malformations are the most unpredictable and dangerous congenital
      malformations. They consist of multiple arteriovenous shunts with high flow and
      can progress to heart failure. They are rarely localized in the upper limb and
      pose therapeutic problems. We report a new case in a 27-year old woman, admitted
      for pulsatile pain in the left elbow. The diagnosis was made by clinical
      examination and ultrasonography. The surgical treatment without embolization and
      sclerotherapy, consisted of a large resection of the nidus without postoperative
      complication. 

PMID- 24035260
TI  - [Risk factor for deep venous thrombosis in internal medicine: A retrospective
      study of 318 cases].
AB  - OBJECTIVE: Venous thromboembolic disease is a common condition. Deep vein
      thrombosis (DVT) and pulmonary embolism are the most common manifestation but
      other locations may also occur. The objectives of the study were to estimate the
      incidence and determine the epidemiologic, topographic and associated conditions
      of venous thromboembolic disease in a department of internal medicine. METHODS: A
      retrospective study of a series of 318 cases of DVT was conducted in Internal
      Medicine CHU Hedi Chaker, Sfax, during a period of 15 years (1996-2010). RESULTS:
      DVT of the lower limbs was the most common location (87%). Other sites of DVT was
      noted in 16.35% of cases including upper limbs (19 cases), vena cava (16 cases),
      cerebral veins (10 cases), portal vein (10 cases) and hepatic vein (3 cases). A
      risk factor of VTE was found in 274 patients (86.1%). A state of thrombophilia
      was retained in 203 patients (63.5%). It was a hereditary thrombophilia (22.6%),
      an antiphospholipids syndrome (19.1%), Behcet's disease (16.4%) and neoplasia
      (7.2%). The study of the distribution of venous thrombosis as the seat and
      etiology showed that: the antiphospholipid syndrome was the most associated
      conditions with the upper extremity DVT (31.7%) whereas Behcet's disease was the
      most frequent etiology of vena cava thrombosis (7 cases) and the cerebral vein
      thrombosis especially in young males.

PMID- 24035261
TI  - A life-threatening complication of parenteral nutrition: how to prevent cardiac
      tamponade?
AB  - Complications caused by incorrect central venous insertion are numerous. Cardiac
      tamponade is a rare, but well-documented complication that is often lethal. We
      present the case of a patient with cardiac tamponade caused by incorrect tip
      position and infusion of hyperosmolar fluids such as for parenteral nutrition. 

PMID- 24035262
TI  - Integrated laser-guided CT biopsy.
AB  - The diagnostic yield of computed tomography (CT)-guided biopsies is dependent on
      accurate needle insertion. A laser-assisted angle selection system was custom
      fabricated and used during a CT-guided lung biopsy. Off-target error was measured
      comparing standard methods to the laser method while pointing towards the target
      from the skin. The difference between the planned angle and selected angle using
      the laser-assisted system was 2 degrees , improved from 12 degrees  with the
      standard method. Although yet to be confirmed, laser-assisted angle selection
      systems may improve the accuracy of needle placement, which may translate into
      improved outcomes for certain needle based procedures. 

PMID- 24035263
TI  - FDG PET in the evaluation of phaeochromocytoma: a correlative study with MIBG
      scintigraphy and Ki-67 proliferative index.
AB  - To compare 123I-metaiodobenzylguanidine (MIBG) and [Fluorine-18]-2-fluoro-2-deoxy
      D-glucose (FDG) positron emission tomography (PET) in 22 patients with
      phaeochromocytomas and paragangliomas (PGL) retrospectively and to evaluate the
      correlation between FDG uptake and Ki-67 proliferative index. Fourteen of 17
      (82%) patients at initial diagnosis had positive FDG uptake, more intensely in
      PGL. Eleven of 12 (92%) patients had positive MIBG uptake. PET and MIBG
      scintigraphy were concordant in 10 patients, discordant in 6. Combined results
      yielded no false negative findings and are complementary. Neither maximum
      standardised uptake value nor visual scores on MIBG correlated with Ki-67.

PMID- 24035264
TI  - Development and validation of an attenuated Mycoplasma hyopneumoniae aerosol
      vaccine.
AB  - Mycoplasma hyopneumoniae (M. hyopneumoniae) causes a chronic respiratory disease
      with high morbidity and low mortality in swine, and has been presented as a major
      cause of growth retardation in the swine industry. Aerosol vaccination presents a
      needle free, high throughput, and efficient platform for vaccine delivery, and
      has been widely applied in poultry vaccination. However, aerosol vaccines have
      rarely been used in swine vaccination primarily because the long and curving
      respiratory track of swine presents a barrier for vaccine particle delivery. To
      develop an effective M. hyopneumoniae aerosol vaccine, three major barriers need
      to be overcome: to optimize particle size for aerosol delivery, to maintain the
      viability of mycoplasma cells in the vaccine, and to optimize the environmental
      conditions for vaccine delivery. In this study, an aerosol mycoplasma vaccine was
      successfully developed based on a conventional live attenuated M. hyopneumoniae
      vaccine. Specifically, the Pari LCD nebulizer was used to produce an aerosol
      vaccine particle size less than 5 MUm; and a buffer with 5% glycerol was
      developed and optimized to prevent inactivation of M. hyopneumoniae caused by
      aerosolization and evaporation. Before nebulization, the room temperature and
      relative humidity were control to 20-25  degrees C and 70-75%, respectively,
      which helped maintain the viability of aerosol vaccine. Animal experiments
      demonstrated that this newly developed aerosol vaccine was effectively delivered
      to swine low respiratory track, being confirmed by nested-PCR, in situ
      hybridization and scanning electron microscope. Moreover, M. hyopneumoniae
      specific sIgA secretion was detected in the nasal swab samples at 14 days post
      immunization. To our knowledge, this is the first report on a live M.
      hyopneumoniae aerosol vaccine.

PMID- 24035265
TI  - Vaccination inhibits TLR2 transcription via suppression of GR nuclear
      translocation and binding to TLR2 promoter in porcine lung infected with
      Mycoplasma hyopneumoniae.
AB  - Toll-like receptors (TLRs) and glucocorticoid receptor (GR) act respectively as
      effectors of innate immune and stress responses. The crosstalk between them is
      critical for the maintenance of homeostasis during the immune response.
      Vaccination is known to boost adaptive immunity, yet it remains elusive whether
      vaccination may affect GR/TLR interactions following infection. Duroc*Meishan
      crossbred piglets were allocated to three groups. The control group (CC) received
      neither vaccination nor infection; the non-vaccinated infection group (NI) was
      artificially infected intratracheally with Mycoplasma hyopneumoniae (M.
      hyopneumoniae); while the vaccinated, infected group (VI) was vaccinated
      intramuscularly with inactivated M. hyopneumoniae one month before infection. The
      clinical signs and macroscopic lung lesions were significantly reduced by
      vaccination. However, vaccination did not affect the concentration of M.
      hyopneumoniae DNA in the lung. Serum cortisol was significantly decreased in both
      NI and VI pigs (P<0.01), but only VI pigs demonstrated significantly diminished
      nuclear GR content. TLRs 1-10 were all expressed in lung, among which TLR2 was
      the most abundant and was significantly up-regulated (P<0.05) in NI pigs, but not
      in VI pigs. Accordingly, GR binding to the GR response element on TLR2 promoter
      was significantly increased (P<0.05) in NI pigs, but not in VI pigs. These
      results suggest that the inhibition of GR nuclear translocation and binding to
      the TLR2 promoter, which results in diminished TLR2 expression, is associated
      with the protective effect of vaccination on M. hyopneumoniae-induced lung
      lesions in the pig. 

PMID- 24035266
TI  - Molecular characterization and phylogenetic analysis of deformed wing viruses
      isolated from South Korea.
AB  - Deformed wing virus (DWV) is one of the most common viral infection in honeybees.
      Phylogenetic trees were constructed for 16 partial nucleotide sequences of the
      structural polyprotein region and the RNA helicase region of South Korean DWVs.
      The sequences were compared with 10 previously reported DWV sequences from
      different countries and the sequences of two closely related viruses, Kakugo
      virus (KGV) and Varroa destructor virus-1 (VDV-1). The phylogeny based on these
      two regions, the Korean DWV genomes were highly conserved with 95-100% identity,
      while they also shared 93-97% similarity with genotypes from other countries,
      although they formed a separate cluster. To investigate this phenomenon in more
      detail, the complete DWV genome sequences of Korea-1 and Korea-2 were determined
      and aligned with six previously reported complete DWV genome sequences from
      different countries, as well as KGV and VDV-1, and a phylogenetic tree was
      constructed. The two Korean DWVs shared 96.4% similarity. Interestingly, the
      Korea-2 genome was more similar to the USA (96.5%) genome than the Korea-1. The
      Korean genotypes highly conserved with USA (96%) but low similarity with the
      United Kingdom3 (UK3) genome (89%). The end of the 5' untranslated region (UTR),
      the start of the open reading frame (ORF) region, and the 3' UTR were variable
      and contained several substitutions/transitions. This phenomenon may be explained
      by intramolecular recombination between the Korean and other DWV genotypes. 

PMID- 24035267
TI  - Suicidal thoughts and attempts among u.s. High school students: trends and
      associated health-risk behaviors, 1991-2011.
AB  - PURPOSE: To describe secular trends in suicidal thoughts and attempts and the
      types of health-risk behaviors associated with suicidal thoughts and attempts
      among U.S. high school students. METHODS: Data were analyzed from 11 national
      Youth Risk Behavior Surveys conducted biennially during 1991-2011. Each survey
      employed a nationally representative sample of students in grades 9-12 and
      provided data from approximately 14,000 students. Using sex-stratified logistic
      regression models that controlled for race/ethnicity and grade, we analyzed
      secular trends in the prevalence of suicidal thoughts and attempts. Adjusted
      prevalence ratios (APR) were calculated to measure associations between suicide
      risk and a broad range of health-risk behaviors. RESULTS: During 1991-2011, among
      female students, both suicidal thoughts (seriously considered suicide; made a
      plan to attempt suicide) and attempts (any attempt; attempt with injury requiring
      medical treatment) decreased significantly; among male students, only suicidal
      thoughts decreased significantly. During 2011, compared with students with no
      suicidal thoughts or attempts, the health-risk behaviors most strongly associated
      with suicide attempts among female students were injection drug use (APR = 12.8),
      carrying a weapon on school property (APR = 9.7), and methamphetamine use (APR =
      8.7); among male students, the strongest associations were for IDU (APR = 22.4),
      using vomiting/laxatives for weight control (APR = 17.1), and having been forced
      to have sex (APR = 14.8). CONCLUSIONS: School-based suicide prevention programs
      should consider confidential screening for health-risk behaviors that are
      strongly associated with suicide attempts to help identify students at increased
      risk for suicide and provide referrals to suicide and other prevention services
      (e.g., substance abuse and violence prevention) as appropriate.

PMID- 24035268
TI  - [From professional medical responsibility to clinical safety].

PMID- 24035269
TI  - [Psychotropics and pain while driving].

PMID- 24035270
TI  - Elevated CSF and plasma microparticles in a rat model of streptozotocin-induced
      cognitive impairment.
AB  - Alzheimer's disease (AD), can be described as a vascular disorder, is
      characterized by endothelial and platelet activation. One feature of activated
      cells is loss of lipid asymmetry, and membrane blebbing which cause microparticle
      (MP) formation. MPs increased under many pathological states and little
      information is available relating to their changes in AD. The purpose of this
      work was to characterize the time course of the endothelial-derived
      microparticles (EMPs) and platelet-derived microparticles (PMPs) alteration after
      intracerebroventricular (ICV) injection of streptozotocin (STZ). Rats were
      injected bilaterally with ICV-STZ/Saline, cerebrospinal fluid (CSF) and plasma
      EMPs (Annexin V(+) CD61(-)CD144(+)) and PMPs (Annexin V(+) CD61(+)CD144(-)) were
      analyzed with flow cytometry at 2 h, 4 h, 24 h, 4 days, 7 days, 14 days and 21
      days after ICV-STZ/Saline administration. Cognitive impairment, malondialdehyde
      (MDA) level of hippocampus, plasma serotonin, and serum S100B were also assessed.
      We showed the elevation of CSF and plasma level of EMPs and PMPs, which may
      represent a proinflammatory and prothrombotic status. These alterations were
      simultaneous with the hippocampal MDA rise, plasma serotonin increment, and S100B
      decrement, 7 days after ICV-STZ administration and precede the onset of cognitive
      impairment. Understanding the profile of MP changes in CSF or plasma as
      biomarkers from tissues undergoing activation or damage, may be helpful in
      prediction or early diagnosis of AD.

PMID- 24035271
TI  - Eosinophlic pneumonia in a patient with anticentromere antibody.

PMID- 24035272
TI  - Role of urethral bulking agents in epispadias-exstrophy complex patients.
AB  - OBJECTIVE: Injection of urethral bulking agents (UBA) has been used to increase
      bladder capacity prior to bladder neck reconstruction (BNR) or as an adjuvant
      therapy following BNR to improve continence. The purpose of this study was to
      determine the effectiveness of urethral injections in the exstrophy population.
      MATERIALS AND METHODS: A review was performed of patient characteristics, bladder
      capacity, and continence status of all patients with the exstrophy-epispadias
      complex who underwent injection of UBA between 1980 and 2008. RESULTS: Among 66
      patients with a median follow-up of 8 years, 41 underwent injections prior to
      BNR, and 25 had injections after BNR. Only 24% of patients who underwent
      injections prior to BNR were continent on last follow-up. Among 25 patients who
      underwent BNR prior to injection(s), 16 were partially continent and nine were
      incontinent prior to first injection. Patients who were partially continent
      attained social continence (dry interval greater than 3 h) at a significantly
      higher rate than those who were incontinent (63% vs. 13%, p = 0.047). No patient
      with cloacal exstrophy in either group attained urethral continence. CONCLUSION:
      UBAs do not appear to have a role prior to BNR. However, they may provide benefit
      when given adjunctively following BNR in patients who are partially continent.

PMID- 24035273
TI  - Feasibility of using a compact elliptical device to increase energy expenditure
      during sedentary activities.
AB  - OBJECTIVES: This study aimed to evaluate the feasibility of using a compact
      elliptical device to increase energy expenditure during sedentary activities. A
      secondary aim was to evaluate if two accelerometers attached to the elliptical
      device could provide reliable and valid assessments of participants' frequency
      and duration of elliptical device use. DESIGN: Physically inactive adults (n=32,
      age range=25-65) were recruited through local advertisements and selected using
      stratified random sampling based on sex, body mass index (BMI), and age. METHODS:
      Indirect calorimetry was used to assess participants' energy expenditure while
      seated and while using the elliptical device at a self-selected intensity level.
      Participants also self-reported their interest in using the elliptical device
      during sedentary activities. Two Actigraph GT3X accelerometers were attached to
      the elliptical device to record time-use patterns. RESULTS: Participants expended
      a median of 179.1 kilocalories per hour while using the elliptical device
      (range=108.2-269.0), or a median of 87.9 more kilocalories (range=19.7-178.6)
      than they would expend per hour of sedentary sitting. Participants reported high
      interest in using the elliptical device during TV watching and computer work, but
      relatively low interest in using the device during office meetings. Women
      reported greater interest in using the elliptical device than men. The two
      accelerometers recorded identical time-use patterns on the elliptical device and
      demonstrated concurrent validity with time-stamped computer records. CONCLUSIONS:
      Compact elliptical devices could increase energy expenditure during sedentary
      activities, and may provide proximal environmental cues for increasing energy
      expenditure across multiple life domains.

PMID- 24035274
TI  - Prostaglandin I2-IP signalling regulates human Th17 and Treg cell
      differentiation.
AB  - Prostaglandin I2 (PGI2) is an important immunoregulatory lipid mediator. In this
      study, we analysed the effects of the PGI2 analogue (Iloprost) on the
      differentiation of Th17 cells and Tregs from human naive CD4(+) T cells. PGI2
      receptors (IP) are expressed on human naive CD4(+) T cells. Via IP binding, the
      PGI2 analogue decreased the proportion of Tregs and Foxp3 mRNA expression but
      increased the percentage of Th17 cells, RORC mRNA and IL-17A production. The
      regulatory effects of Iloprost correlated with elevated intracellular cAMP
      levels. The effects were mimicked by a cAMP agonist (db-cAMP) but attenuated by a
      protein kinase A inhibitor (H-89). STAT3 and STAT5 signalling play direct and
      crucial roles in the development of Th17 and Tregs, respectively. The PGI2
      analogue enhanced the activation of STAT3 in response to IL-6, whereas it
      decreased STAT5 activation in response to IL-2. Moreover, db-cAMP imitated the
      above effects of Iloprost, which were weakened by H-89. These results demonstrate
      that the PGI2-IP interaction promoted the phosphorylation of STAT3 and reduced
      the phosphorylation of STAT5, likely via the upregulation of cAMP-PKA signalling,
      thus facilitated Th17 differentiation and suppressed Treg differentiation.
      Together with previous results, these data suggest that prostanoids play an
      important role in the pathogenesis of autoimmune diseases, such as rheumatoid
      arthritis. 

PMID- 24035275
TI  - Paraneoplastic cerebellar degeneration with anti-Yo antibodies associated with
      metastatic uveal melanoma.
AB  - Paraneoplastic cerebellar degeneration (PCD) is characterized by subacute
      development of pancerebellar dysfunction as a remote effect of a systemic cancer
      and usually develops in patients affected by gynecological tumors. Uveal melanoma
      is a very rare disease with a severe prognosis. A 58-year-old man affected by
      uveal melanoma developed anti-Yo positive paraneoplastic cerebellar degeneration
      (PCD) 42 months after the initial diagnosis. The onset and worsening of the
      neurological symptoms were parallel to the course of liver metastasis. To our
      knowledge this is the first case of PCD in a patient with uveal melanoma. We
      speculate that the cerebellar degeneration-related protein 2 (CDR2), to which the
      anti-Yo antibodies are directed, may have been expressed in melanoma cells and
      conferred proliferative advantage to the disease.

PMID- 24035276
TI  - Magnetic resonance spectroscopy as a predictor of conversion of mild cognitive
      impairment to dementia.
AB  - BACKGROUND AND PURPOSE: Proton magnetic resonance spectroscopy ((1)H-MRS) is one
      of the imaging techniques that could be potentially useful for identification of
      patients with mild cognitive impairment (MCI) who are at increased risk of
      developing dementia. The aim of the study was to investigate if there is a
      difference in brain metabolism between stable MCI patients and converters to
      dementia and if a use of (1)H-MRS can predict the conversion from MCI to
      dementia. MATERIAL AND METHODS: Forty-one amnestic MCI patients and 35
      cognitively unimpaired controls were examined by (1)H-MRS (TE - 35 ms) at
      baseline. Metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr, Glx/Cr, NAA/Cho) were
      estimated in four different brain regions: posterior cingulate gyrus (PCG), left
      hippocampus (LH), cortical area of right (RPL) and left parietal lobe (LPL).
      Participants were followed up for a period of 12 months. RESULTS: Twelve subjects
      with MCI progressed to Alzheimer's disease (AD) after one year. Analysis showed
      that the NAA/Cr ratio in the LH was significantly lower in MCI patients than in
      controls (p=0.008), but there were no differences in metabolite ratios at
      baseline between MCI converters and stable subjects. mI/Cr ratio in RPL predicted
      the conversion to AD with sensitivity 70% and specificity 85% (p<0.0004).
      Coexistence of diabetes improved prediction, yielding 70% sensitivity and 96%
      specificity (p<0.0001). CONCLUSIONS: (1)H-MRS in MCI can be a predictor of
      cognitive decline and conversion to dementia, especially in MCI patients with
      coexisting diabetes. Further studies are needed to confirm this finding.

PMID- 24035277
TI  - Retrotransposon replication in plants.
AB  - Retrotransposons comprise the bulk of large plant genomes, replicating via an RNA
      intermediate whereby the original, integrated element remains in place. Of the
      two main orders, the LTR retrotransposons considerably outnumber the LINEs. LINEs
      integrate into target sites simultaneously with the RNA transcript being copied
      into cDNA by target-primed reverse transcription. LTR retrotransposon replication
      is basically equivalent to the intracellular phase of retroviral life cycles. The
      envelope gene giving extracellular mobility to retroviruses is in fact widespread
      in plants and their retrotransposons. Evolutionary analyses of the
      retrotransposons and retroviruses suggest that both form an ancient monophyletic
      group. The particular adaptations of LTR retrotransposons to plant life cycles
      enabling their success remain to be clarified. 

PMID- 24035278
TI  - Pharmacokinetic variability of clarithromycin and differences in CYP3A4 activity
      in patients with cystic fibrosis.
AB  - BACKGROUND: To investigate the correlation between CYP3A4/5 activity and
      clarithromycin metabolism, and between CYP3A activity and CYP3A genotype.
      METHODS: This is an open-label, prospective pharmacokinetic study evaluating
      CYP3A activity using The Erythromycin Breath Test. Eight blood samples were
      collected within 12h after clarithromycin 500 mg was administered orally. The
      clarithromycin concentrations were measured by liquid chromatography-tandem mass
      spectrometry. AUC, Tmax and Cmax were calculated. Selected Single Nucleotide
      polymorphisms in CYP3A4/5 genes were assessed by PCR and single base extension.
      RESULTS: Twenty-one chronically infected patients were included. An 8-fold
      variation in the CYP3A4 activity, 10-fold variation in AUC for clarithromycin
      (median 881 MUg/mL * min), and a 16-fold variation in Cmax for clarithromycin
      (median 3.4 MUg/mL) were found. A linear correlation between the CYP3A4-activity
      and clarithromycin metabolism was demonstrated (P < 0.05). CONCLUSION: The large
      variation in the clarithromycin pharmacokinetics in cystic fibrosis patients may
      cause treatment failure. The Erythromycin Breath Test could be valuable in
      identifying cystic fibrosis patients in risk of treatment failure/drug toxicity.

PMID- 24035279
TI  - Overview of factors that affect comfort with modern soft contact lenses.

PMID- 24035280
TI  - Clinicopathological significance of SIRT1 and p300/CBP expression in
      gastroesophageal junction (GEJ) cancer and the correlation with E-cadherin and
      MLH1.
AB  - SIRT1 and p300/CBP, which are considered to be essential histone deacetylases and
      acetyltransferases, are also considered to be relative to tumorigenesis because
      they modulate the expression of several tumor suppressor genes. Therefore, this
      study investigated the expression of SIRT1 and p300/CBP in gastroesophageal
      junction (GEJ) cancer and their correlation with E-cadherin and MLH1 in order to
      explore the clinicopathological significance of SIRT1 and p300/CBP expression and
      their possible effects involving E-cadherin and MLH1 expression. Tissue
      microarray technique and immunohistochemical stains were applied to evaluate the
      SIRT1, p300/CBP, E-cadherin, and MLH1 expression in 176 GEJ cancer tissues and 32
      normal GEJ region tissues. The results showed that the over-expression of SIRT1
      was associated with a higher number of metastasis lymph nodes, more advanced
      staging, and shorter mean survival time. SIRT1 and p300/CBP were negatively and
      positively correlated with the expression of E-cadherin and MLH1, respectively,
      in the cancer cases. These results indicated a possible effect of SIRT1 and
      p300/CBP involved in regulating the expression of E-cadherin and MLH1, thus
      participating in the tumor progression of GEJ cancer. 

PMID- 24035281
TI  - Evaluation of performance of A1c and FPG tests for screening newly diagnosed
      diabetes defined by an OGTT among tuberculosis patients-a study from India.
AB  - AIM: The methods used for diagnosis of diabetes have limitations particularly in
      situations associated with stress hyperglycemia. Aim of this study was to
      evaluate the performance of A1c and fasting plasma glucose (FPG) tests for
      screening newly diagnosed diabetes (NDD) defined by OGTT among tuberculosis (TB)
      cases in India. METHODS: A total of 983 subjects aged >=18 years with TB were
      selected from 7 TB units - 4 urban, 2 rural and 1 semi-urban areas of Tamil Nadu,
      India, during August 2010-March 2011. Screening for diabetes was carried out by 2
      h 75g OGTT. Classification of glucose intolerance status was based on WHO
      criteria. HbA1c was measured by high performance liquid chromatography using Bio
      Rad turbo machine. HbA1c>=47.5mmol/mol was used for diagnosis of diabetes. FPG
      was estimated by glucose-oxidase method. Known cases of subjects with diabetes
      were excluded and final analysis was done using data of 779 individuals. The
      performance of A1c and FPG tests was evaluated against the results of OGTT using
      receiver operating characteristic curve analysis. RESULTS: Prevalence of NDD was
      10.8%. The areas under the curve (AUC) were 0.754 [95% confidence interval (CI)
      0.68-0.83] (p<0.001) for A1c and 0.662 (95% CI 0.58-0.74) for FPG (p<0.001) in
      NDD subjects. The HbA1c cut-off point of >=47.5mmol/mol gave a sensitivity of
      59.1% and specificity of 91.7%, and the respective values were 34.8% and 97.5%
      for FPG in subjects with NDD. CONCLUSION: HbA1c performed better than FPG as a
      screening tool for newly diagnosed diabetes among subjects with TB.

PMID- 24035282
TI  - Modulation of curli assembly and pellicle biofilm formation by chemical and
      protein chaperones.
AB  - Enteric bacteria assemble functional amyloid fibers, curli, on their surfaces
      that share structural and biochemical properties with disease-associated
      amyloids. Here, we test rationally designed 2-pyridone compounds for their
      ability to alter amyloid formation of the major curli subunit CsgA. We identified
      several compounds that discourage CsgA amyloid formation and several compounds
      that accelerate CsgA amyloid formation. The ability of inhibitor compounds to
      stop growing CsgA fibers was compared to the same property of the CsgA chaperone,
      CsgE. CsgE blocked CsgA amyloid assembly and arrested polymerization when added
      to actively polymerizing fibers. Additionally, CsgE and the 2-pyridone inhibitors
      prevented biofilm formation by Escherichia coli at the air-liquid interface of a
      static culture. We demonstrate that curli amyloid assembly and curli-dependent
      biofilm formation can be modulated not only by protein chaperones, but also by
      "chemical chaperones."

PMID- 24035283
TI  - Optical and radioiodinated tethered Hsp90 inhibitors reveal selective
      internalization of ectopic Hsp90 in malignant breast tumor cells.
AB  - Inhibitors of heat-shock protein 90 (Hsp90) have demonstrated an unusual
      selectivity for tumor cells despite its ubiquitous expression. This phenomenon
      has remained unexplained, but could be influenced by ectopically expressed Hsp90
      in tumors. In this work, we synthesized Hsp90 inhibitors that can carry optical
      or radioiodinated probes via a polyethyleneglycol tether. We show that these
      tethered inhibitors selectively recognize cells expressing ectopic Hsp90 and
      become internalized. The internalization process is blocked by Hsp90 antibodies,
      suggesting that active cycling of the protein occurs at the plasma membrane. In
      mice, we observed exquisite accumulation of the fluor-tethered versions within
      breast tumors at very sensitive levels. Cell-based assays with the radiolabeled
      version showed picomolar detection in cells that express ectopic Hsp90. Our
      findings show that fluor-tethered or radiolabeled inhibitors that target ectopic
      Hsp90 can be used to detect breast cancer malignancies through noninvasive
      imaging. 

PMID- 24035285
TI  - Opioid system genes in alcoholism: a case-control study in Croatian population.
AB  - Due to their involvement in dependence pathways, opioid system genes represent
      strong candidates for association studies investigating alcoholism. In this
      study, single nucleotide polymorphisms within the genes for mu (OPRM1) and kappa
      (OPRK1) opioid receptors and precursors of their ligands - proopiomelanocortin
      (POMC), coding for beta-endorphin and prodynorphin (PDYN) coding for dynorphins,
      were analyzed in a case-control study that included 354 male alcohol-dependent
      and 357 male control subjects from Croatian population. Analysis of allele and
      genotype frequencies of the selected polymorphisms of the genes OPRM1/POMC and
      OPRK1/PDYN revealed no differences between the tested groups. The same was true
      when alcohol-dependent persons were subdivided according to the Cloninger's
      criteria into type-1 and type-2 groups, known to differ in the extent of genetic
      control. Thus, the data obtained suggest no association of the selected
      polymorphisms of the genes OPRM1/POMC and OPRK1/PDYN with alcoholism in Croatian
      population. 

PMID- 24035284
TI  - The determinants of activity and specificity in actinorhodin type II polyketide
      ketoreductase.
AB  - In the actinorhodin type II polyketide synthase, the first polyketide
      modification is a regiospecific C9-carbonyl reduction, catalyzed by the
      ketoreductase (actKR). Our previous studies identified the actKR 94-PGG-96 motif
      as a determinant of stereospecificity. The molecular basis for reduction
      regiospecificity is, however, not well understood. In this study, we examined the
      activities of 20 actKR mutants through a combination of kinetic studies, PKS
      reconstitution, and structural analyses. Residues have been identified that are
      necessary for substrate interaction, and these observations have suggested a
      structural model for this reaction. Polyketides dock at the KR surface and are
      steered into the enzyme pocket where C7-C12 cyclization is mediated by the KR
      before C9-ketoreduction can occur. These molecular features can potentially serve
      as engineering targets for the biosynthesis of novel, reduced polyketides. 

PMID- 24035286
TI  - Ultrasonic and thermal pretreatments to enhance the anaerobic bioconversion of
      olive husks.
AB  - Olive husks, typical solid by-products from the olive oil industry, were selected
      to carry out anaerobic digestion tests. Before digestion, olive husks were
      subjected to ultrasonic or thermal pretreatments in order to release the organic
      matter into solution. Both sonication and thermal pretreatment allowed to
      solubilize the particulate matter with 22% and 72% increase in soluble organics
      of olive husks, respectively. Nevertheless, such pretreatments caused the release
      of unwanted molecules in solution, with the related risks of inhibition of the
      methanogenic process. Biochemical Methane Potential (BMP) tests on olive husks
      mixed with olive-mill wastewater and dairy wastewater, either pretreated or not,
      showed that ultrasound pretreatment resulted in 15% increase in volatile solids
      reduction and a 13% increase in biogas production, while after thermal
      pretreatment no benefits were observed. 

PMID- 24035287
TI  - Maxillofacial fractures in the province of Latina, Lazio, Italy: review of 400
      injuries and 83 cases.
AB  - A retrospective study was performed to assess maxillofacial fractures in patients
      treated at the public "S.M. Goretti Hospital" hospital from 2011 to 31/8/2012.
      Data were prospectively recorded including age and sex, cause and mechanisms of
      injury, soft tissue injuries, dentoalveolar trauma, facial bone fractures and
      type of treatment. The pre-surgical and post-surgical hospitalization days were
      also analysed. Causes were grouped into five categories: road traffic collision,
      sports accidents, occupational accidents, assaults and domestic accidents. The
      analyses involved descriptive statistics. Records from 83 patient sustaining 95
      maxillofacial fractures were evaluated. The zygoma was the most fractured
      anatomical site in both males and females, accounting for 32% of injuries,
      followed by isolated fracture of the orbital floor (blow-out and blow-in) with
      11%. The age group between 18 and 39 years showed the highest rate of incidence
      of maxillofacial fractures. Men were more involved than women in all cases with a
      male:female ratio of 5,4:1. Accidents were the most frequent cause of
      maxillofacial fractures in the age group between 18 and 39 years and
      interpersonal violence was the most frequent cause of maxillofacial fractures in
      the age group between 40 and 59 years. Facial fractures occurred primarily among
      men under 30 years of age, and the most common sites of fractures in the face
      were the mandible and the zygomatic complex. Road traffic collisions were the
      main aetiologic factor associated with maxillofacial trauma. 

PMID- 24035288
TI  - The use of resorbable plates in association with dental arch stabilization in the
      treatment of mandibular fractures in children.
AB  - PURPOSE: The purpose of this study was to investigate the effect of resorbable
      plate fixation in association with dental arch stabilization in the treatment of
      displaced mandibular fractures in children. PATIENTS AND METHODS: Thirteen
      children (5 girls and 8 boys, age range 2 years 5 months to 12 years 2 months)
      with displaced mandibular fractures were included in this case series. Open
      reduction by intraoral approach was performed on these patients, and the
      fractures were fixed using resorbable plates and monocortical screws placed at
      the lower border of the mandible. At the same time, an arch bar or orthodontic
      wire splint was anchored using stainless steel wires or resin on the teeth to
      stabilize the whole mandibular dental arch. Postoperatively, follow-up was
      undertaken to evaluate the fracture healing, mandible movement, and mandible
      growth. RESULTS: Postoperatively, all patients achieved uneventful healing;
      premorbid occlusion restoration and wound healing were achieved, along with
      unimpaired function and normal growth and development of the mandible.
      Complications such as damage to tooth buds, infection, malunion, and nonunion
      were not encountered in these patients. CONCLUSION: Resorbable plates use in
      association with dental arch stabilization can provide good stabilization for
      mandibular fractures and is a promising approach for the treatment of displaced
      mandibular fractures in children.

PMID- 24035289
TI  - Canadian Cardiovascular Society position statement on radiation exposure from
      cardiac imaging and interventional procedures.
AB  - Exposure to ionizing radiation is a consequence of many diagnostic and
      interventional cardiac procedures. Radiation exposure can result in detrimental
      health effects because of deterministic (eg, skin reaction) and stochastic
      effects (eg, cancer). However, with the levels experienced during cardiac
      procedures these risks can be difficult to quantify. Healthcare providers and
      patients might not fully appreciate radiation-related risks. Though in many cases
      radiation exposure cannot be avoided, a practice of minimizing exposures to
      levels "as low as reasonably achievable" (ALARA principle) without compromising
      the utility of the procedure is encouraged. The purpose of this document is to
      inform health care providers on the key concepts related to radiation risk from
      common cardiac procedures and provide specific recommendations on ensuring
      quality of care. 

PMID- 24035291
TI  - Acute disseminated encephalomyelitis associated with dengue infection: a case
      report with literature review.
AB  - Dengue is the commonest arboviral illness caused by four antigenically distinct
      dengue virus serotypes (DEN-1 through DEN-4). The clinical spectrum of the
      disease ranges from asymptomatic or mild infection to catastrophic dengue shock
      syndrome (DSS). In last few years, neurological manifestations of dengue
      infection have been increasingly observed and reported mainly with serotypes DEN
      2 and DEN-3. The pathogenesis of neurological manifestations includes:
      neurotrophic effect of the dengue virus, related to the systemic effects of
      dengue infection, and immune mediated. Encephalopathy and encephalitis are the
      most frequently reported neurological manifestations followed by meningitis,
      myositis, hypokalemic periodic paralysis, stroke, Guillain-Barre syndrome and
      transverse myelitis. Acute disseminated encephalomyelitis (ADEM) associated with
      dengue infection is rarely reported. We herein report a case of ADEM associated
      with classic dengue fever. Favourable clinical outcome occurred after a five-day
      course of intravenous methylprednisolone therapy. 

PMID- 24035292
TI  - Parkinsonism syndrome in heterozygotes for Niemann-Pick C1.
AB  - Niemann-Pick C (NPC) disease is a rare autosomal recessive lipid storage
      disorder. We report here the unique occurrence of three adult heterozygous
      carriers of mutations in the NPC1 gene who also have a parkinsonism syndrome.
      This suggests the possibility that mutations in NPC1 could be a risk factor for
      Parkinson's disease similar to the phenomenon that is now recognized with Gaucher
      disease and the glucocerebrosidase (GBA) gene. This report should be a stimulus
      for larger more detailed epidemiological studies. 

PMID- 24035293
TI  - Clinical experiences with cannabinoids in spasticity management in multiple
      sclerosis.
AB  - INTRODUCTION: Spasticity is a common symptom among patients with multiple
      sclerosis (MS). This study aims to assess the effectiveness and safety of the
      combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in
      clinical practice for the treatment of spasticity in MS. METHODS: Retrospective
      observational study with patients treated with inhaled THC/CBD between April 2008
      and March 2012. Descriptive patient and treatment variables were collected.
      Therapeutic response was evaluated based on the doctor's analysis and overall
      impression. RESULTS: Of the 56 patients who started treatment with THC/CBD, 6
      were excluded because of missing data. We evaluated 50 patients (42% male) with a
      median age 47.8 years (25.6-76.8); 38% were diagnosed with primary progressive
      MS, 44% with secondary progressive MS, and 18% with relapsing-remitting MS. The
      reason for prescribing the drug was spasticity (44%), pain (10%), or both (46%).
      Treatment was discontinued in 16 patients because of ineffectiveness (7
      patients), withdrawal (4), and adverse effects (5). The median exposure time in
      patients whose treatment was discontinued was 30 days vs 174 days in those whose
      treatment continued at the end of the study. THC/CBD was effective in 80% of
      patients at a median dose of 5 (2-10) inhalations/day. The adverse event profile
      consisted of dizziness (11 patients), somnolence (6), muscle weakness (7), oral
      discomfort (2), diarrhoea (3), dry mouth (2), blurred vision (2), agitation (1),
      nausea (1), and paranoid ideation (1). CONCLUSIONS: THC/CBD appears to be a good
      alternative to standard treatment as it improves refractory spasticity in MS and
      has an acceptable toxicity profile.

PMID- 24035294
TI  - Analysis of stroke care resources in Spain in 2012: have we benefitted from the
      Spanish Health System's stroke care strategy?
AB  - INTRODUCTION: The Spanish Health System's stroke care strategy (EISNS) is a
      consensus statement that was drawn up by various government bodies and scientific
      societies with the aim of improving quality throughout the care process and
      ensuring equality among regions. Our objective is to analyse existing healthcare
      resources and establish whether they have met EISNS targets. MATERIAL AND
      METHODS: The survey on available resources was conducted by a committee of
      neurologists representing each of Spain's regions; the same committee also
      conducted the survey of 2008. The items included were the number of stroke units
      (SU), their resources (monitoring, neurologists on call 24h/7d, nurse ratio,
      protocols), SU bed ratio/100,000 inhabitants, diagnostic resources (cardiac and
      cerebral arterial ultrasound, advanced neuroimaging), performing iv thrombolysis,
      neurovascular interventional radiology (neuro VIR), surgery for malignant middle
      cerebral artery (MCA) infarctions and telemedicine availability. RESULTS: We
      included data from 136 hospitals and found 45 Stroke Units distributed unequally
      among regions. The ratio of SU beds to residents ranged from 1/74,000 to
      1/1,037,000 inhabitants; only the regions of Cantabria and Navarre met the
      target. Neurologists performed 3,237 intravenous thrombolysis procedures in 83
      hospitals; thrombolysis procedures compared to the total of ischaemic strokes
      yielded percentages ranging from 0.3 to 33.7%. Hospitals without SUs showed
      varying levels of available resources. Neuro VIR is performed in every region
      except La Rioja, and VIR is only available on a 24h/7 d basis in 17 cities.
      Surgery for malignant MCA infarction is performed in 46 hospitals, and 5 have
      telemedicine. CONCLUSION: Stroke care has improved in terms of numbers of
      participating hospitals, the increased use of intravenous thrombolysis and
      endovascular procedures, and surgery for malignant MCA infarction. Implementation
      of SUs and telemedicine remain insufficient. The availability of diagnostic
      resources is good in most SUs and irregular in other hospitals. Regional
      governments should strive to ensure better care and territorial equality, which
      would achieve the EISNS objectives.

PMID- 24035295
TI  - Use of ergotamine: do physicians in Colombia know how to prescribe it?
AB  - INTRODUCTION: Ergot derivatives are drugs with vasoconstrictor effects that are
      used to abort migraine attacks. This study aims to determine how ergot
      derivatives are prescribed by physicians in Colombia, find variables associated
      with inappropriate prescribing, and review potential interactions in our
      patients. METHODS: We reviewed 86 411 formulas during April 2012, identifying the
      prescription by drug, dose, interval, duration of use, and indication. We
      interviewed 288 randomly selected patients in whom we also investigated
      concomitant use of a) antihypertensive agents b) ischaemic heart disease
      treatments c) antiretrovirals d) other antimigraine drugs, and e) macrolides,
      because of their potential for interactions. RESULTS: We identified 801
      prescriptions from patients in 27 cities with a mean age of 35.1+/-14.1 years;
      82.5% of the prescriptions were for women, 96.5% were written by primary care
      physicians, and 65.4% (n=524) corresponded to migraine treatments. There were 26
      different prescription types and 797 prescriptions were incorrect with regard to
      usage recommendations (99.5%). Inappropriate prescribing was significantly
      associated with the health centre providing patient care (P=.005). Of the
      patients who were interviewed by telephone, 266 (92.4%) took the drug according
      to the erroneous indication. A total of 54 patients (6.7%) were treated with
      antihypertensive drugs, 24 (2.9%) with macrolides, and 5 (0.6%) with another
      concomitant antimigraine drug. DISCUSSION: Most patients take ergotamine
      improperly, apart from the fact that potential interactions may increase the risk
      of health problems such as ergotism and coronary events. Physicians will require
      assessment measures, updated information, and continuous training.

PMID- 24035296
TI  - Quality measures in neurology consult care for epileptic patients.
AB  - INTRODUCTION: Epilepsy is one of the most frequently observed diseases in
      neurology outpatient care. METHODS: We analysed our hospital's implementation of
      the 8 epilepsy quality measures proposed by the American Academy of Neurology:
      documented seizure types and seizure frequency, aetiology of epilepsy or the
      epilepsy syndrome, review of EEG, MRI, or CT results, counselling about
      antiepileptic drug side effects, surgical therapy referral for intractable
      epilepsy, and counselling about epilepsy-specific safety issues and for women of
      childbearing age. RESULTS: In most cases, the first four quality measures were
      documented correctly. In 66% of the cases, doctors had asked about any adverse
      drug effects during every visit. Almost all patients with intractable epilepsy
      had been informed about surgical options or referred to a surgical centre of
      reference for an evaluation at some point, although referrals usually took place
      more than 3 years after the initial proposal. Safety issues had been explained to
      37% of the patients and less than half of women of childbearing age with epilepsy
      had received counselling regarding contraception and pregnancy at least once a
      year. CONCLUSIONS: The care we provide is appropriate according to many of the
      quality measures, but we must deliver more counselling and information necessary
      for the care of epileptic patients in different stages of life.

PMID- 24035297
TI  - Benefits of deep encoding in Alzheimer disease. Analysis of performance on a
      memory task using the Item Specific Deficit Approach.
AB  - INTRODUCTION: the aim of this study is to test the encoding deficit hypothesis in
      Alzheimer disease (AD) using a recent method for correcting memory tests. To this
      end, a Spanish-language adaptation of the Free and Cued Selective Reminding Test
      was interpreted using the Item Specific Deficit Approach (ISDA), which provides
      three indices: Encoding Deficit Index, Consolidation Deficit Index, and Retrieval
      Deficit Index. METHODS: We compared the performances of 15 patients with AD and
      20 healthy control subjects and analysed results using either the task
      instructions or the ISDA approach. RESULTS: patients with AD displayed deficient
      encoding of more than half the information, but items that were encoded properly
      could be retrieved later with the help of the same semantic clues provided
      individually during encoding. Virtually all the information retained over the
      long-term was retrieved by using semantic clues. Encoding was shown to be the
      most impaired process, followed by retrieval and consolidation. Discriminant
      function analyses showed that ISDA indices are more sensitive and specific for
      detecting memory impairments in AD than are raw scores. CONCLUSIONS: These
      results indicate that patients with AD present impaired information encoding, but
      they benefit from semantic hints that help them recover previously learned
      information. This should be taken into account for intervention techniques
      focusing on memory impairments in AD.

PMID- 24035298
TI  - Equivalency of right internal thoracic artery and right gastroepiploic artery
      composite grafts: five-year outcomes.
AB  - BACKGROUND: We compared 5-year graft patency rates and long-term clinical
      outcomes after myocardial revascularization using the right internal thoracic
      artery (RITA) and right gastroepiploic artery (RGEA) as a Y-composite graft
      anastomosed to the in situ left internal thoracic artery. METHODS: Of 443
      patients who underwent off-pump coronary revascularization exclusively using
      arterial Y-composite grafts, the RITA (n = 114) or RGEA (n = 329) was anastomosed
      to the side of the in situ left internal thoracic artery. A propensity score
      matched analysis was used to match patients using the RITA (RITA group, n = 105)
      with patients using the RGEA (RGEA group, n = 105). Five-year angiographic
      patency rates and long-term clinical outcomes were compared. RESULTS: There were
      no differences in early mortality and postoperative complication rates between
      the RITA and RGEA groups. Five-year postoperative angiography showed no
      significant differences in overall graft patency (95.0% versus 95.1%; p = 0.895)
      and second-limb conduit patency (RITA versus RGEA, 93.4% versus 92.1%; p = 0.704)
      rates between the two groups. Propensity score-adjusted multivariable analysis
      revealed that previous history of percutaneous coronary intervention was the only
      significant risk factor for second-limb conduit occlusion at 5 years
      postoperatively (p = 0.003). No differences in overall survival (p = 0.703) and
      freedom from cardiac death (p = 0.968) rates were observed between the two
      groups. Reintervention-free survival (p = 0.236) and major adverse cardiac and
      cerebrovascular event-free survival (p = 0.704) rates were also similar between
      the two groups. CONCLUSIONS: Total arterial revascularization using RITA and RGEA
      Y-composite grafts based on the in situ left internal thoracic artery showed
      comparable results in terms of 5-year angiographic patency rates and long-term
      clinical outcomes.

PMID- 24035299
TI  - Effect of phrenic nerve palsy on early postoperative lung function after
      pneumonectomy: a prospective study.
AB  - BACKGROUND: The issue of phrenic nerve preservation during pneumonectomy is still
      an unanswered question. So far, its direct effect on immediate postoperative
      pulmonary lung function has never been evaluated in a prospective trial. METHODS:
      We conducted a prospective crossover study including 10 patients undergoing
      pneumonectomy for lung cancer between July 2011 and July 2012. After written
      informed consent, all consecutive patients who agreed to take part in the study
      and in whom preservation of the phrenic nerve during operation was possible, were
      included in the study. Upon completion of lung resection, a catheter was placed
      in the proximal paraphrenic tissue on the pericardial surface. After an initial
      phase of recovery of 5 days all patients underwent ultrasonographic assessment of
      diaphragmatic motion followed by lung function testing with and without induced
      phrenic nerve palsy. The controlled, temporary paralysis of the ipsilateral
      hemidiaphragm was achieved by local administration of lidocaine 1% at a rate of 3
      mL/h (30 mg/h) via the above-mentioned catheter. RESULTS: Temporary phrenic nerve
      palsy was accomplished in all but 1 patient with suspected catheter dislocation.
      Spirometry showed a significant decrease in dynamic lung volumes (forced
      expiratory volume in 1 second and forced vital capacity; p < 0.05) with the
      paralyzed hemidiaphragm. Blood oxygen saturation levels did not change
      significantly. CONCLUSIONS: Our results show that phrenic nerve palsy causes a
      significant impairment of dynamic lung volumes during the early postoperative
      period after pneumonectomy. Therefore, in these already compromised patients,
      intraoperative phrenic nerve injury should be avoided whenever possible.

PMID- 24035300
TI  - Endobronchial ultrasound-guided transbronchial needle aspiration in diagnosing
      intrathoracic tuberculosis.
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is a minimally invasive procedure that has enabled mediastinal and
      hilar lymph node assessment with a high sensitivity, but its role in the
      diagnosis of intrathoracic tuberculosis (TB) has not been established. METHODS:
      We prospectively studied 59 patients suspected of having TB with thoracic lymph
      node lesions or intrapulmonary lesions accessible by EBUS-TBNA at a clinical
      center for thoracic medicine from January 2010 to December 2011. Bronchoscopic
      findings, EBUS-TBNA procedures, pathologic findings, and microbiologic results
      were recorded. RESULTS: Of 59 eligible patients, 41 patients had TB, 5 had lung
      cancer, 7 had inflammation, and 6 had sarcoidosis. Sensitivity was 85%,
      specificity was 100%, positive and negative predictive values were 100% and 75%,
      respectively, and accuracy was 90% by EBUS-TBNA for TB. Pathologic findings were
      consistent with TB in 80% of patients (33 of 41), and in 27% (11 of 41) the smear
      was positive. A total of 37 patients with TB had cultures, of whom 17 (46%) were
      positive. There were 80 mediastinal and hilar lymph nodes and 5 intrapulmonary
      lesions that were biopsied in the 41 patients with TB. Multivariate logistic
      regression revealed that short-axis diameter was an independent risk factor
      associated with positive pathology, smear, and culture (p < 0.05). Additionally,
      pathology showing necrosis was an independent risk factor associated with a
      positive culture. CONCLUSIONS: Endobronchial ultrasound-guided transbronchial
      needle aspiration has a high diagnostic yield in the investigation of suspected
      intrathoracic TB by means of aspiration of intrathoracic lymph nodes and
      tracheobronchial wall-adjacent lung lesions.

PMID- 24035301
TI  - Extended sleeve lobectomy: one more step toward avoiding pneumonectomy in
      centrally located lung cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate surgical outcomes of
      extended sleeve lobectomy (ESL) in centrally located non-small-cell lung cancer
      (NSCLC), sparing lung tissue and aggressively avoiding pneumonectomy. METHODS:
      Patients who underwent ESL between January 2006 and January 2013 were included
      prospectively. An atypical bronchial anastomosis was used for sleeve lobectomy
      involving additional lobes or segments. RESULTS: We included 27 patients, aged
      62.7 +/- 8.2 years (range, 49-83 years), with a forced expiratory volume in 1
      second (FEV1) of 2.27 +/- 0.6 (range, 1.6-2.7). According to the Okada
      classification, 16 cases were type A (right upper lobe + middle lobe +/- segment
      6), 7 cases were type B (left upper lobe + segment 6), and 2 cases were type C
      (left lower lobe + segments 4-5); we additionally classified 2 patients with
      right lower lobe tumors involving the right main bronchus as type D (right lower
      lobe + middle lobe). Anastomosis was performed between the right superior and
      right main bronchial stumps. Eleven patients underwent combined pulmonary
      angioplasties. Complete resection was achieved in all cases. There were no
      operative deaths. Mean segment reimplantation was 4.5 +/- 0.84 (range, 3-6),
      resulting in a mean FEV1 improvement of 0.620 +/- 0.16 (right-sided ESL) and
      0.393 +/- 0.21 (left-sided ESL). The complication rate was 25% (no immediate
      anastomosis-related complications; 1 case of delayed bronchial stenosis). No
      local recurrence was reported. At 6 months, mean FEV1 was 1.5 +/- 0.4 (right
      sided ESL) and 1.4 +/- 0.3 (left-sided ESL). Mean follow-up time was 28 +/- 19
      months (range, 7-72 months). Overall 5-year survival was 62%. CONCLUSIONS: In
      patients with centrally located NSCLC, lung-sparing ESL, whose safety and
      reliability rival that of pneumonectomy, should be considered. Functional
      effectiveness is higher with right-sided than with left-sided ESL.

PMID- 24035302
TI  - Preoperative atrial fibrillation increases risk of thromboembolic events after
      left ventricular assist device implantation.
AB  - BACKGROUND: Because no series has specifically analyzed the impact of
      preoperative atrial fibrillation (AF) on patients already at higher risk of
      thromboembolism after implantation of a left ventricular assist device (LVAD), we
      review our experience with these patients. METHODS: Between July 2003 and
      September 2011, 389 patients (308 male) underwent implantation of a continuous
      flow LVAD at University of Michigan Hospital and Mayo Clinic. Median age at
      implant was 60 years (range, 18 to 79 years). Preoperative AF was present in 120
      patients (31%). Outcomes were analyzed for the association of preoperative AF and
      postoperative thromboembolic (TE) events defined as stroke, transient ischemic
      attack, hemolysis, or pump thrombosis. Thromboembolic events occurring within the
      first 30 days were not counted. RESULTS: One hundred thirty-eight TEs events
      occurred in 97/389 patients (25%) for an event rate of 0.31 TE events/patient
      years of support. Freedom from a TE event in patients with preoperative AF was
      62% at 1 year and 46% at 2 years compared with 79% and 72% at 1 and 2 years,
      respectively, in patients without preoperative AF (p < 0.001). Median survival
      was 10 months (maximum 7.2 years, total 439 patient-years). Preoperative AF did
      not decrease late survival at 1 and 2 years after LVAD implant (preop AF: 85% and
      70% versus no preop AF: 82% and 70%, respectively; p = 0.55). CONCLUSIONS:
      Patients with preoperative AF have a lower freedom from TE events after LVAD
      implant. While overall late survival was not significantly reduced in these
      patients, refinement in anticoagulation strategies after VAD implant may be
      required.

PMID- 24035303
TI  - Survival after left ventricular assist device with and without temporary right
      ventricular support.
AB  - BACKGROUND: Right ventricular (RV) failure after the insertion of a left
      ventricular assist device (LVAD) historically results in poor outcomes. Patients
      requiring temporary RV support after LVAD insertion are a heterogeneous group of
      patients consisting of those in cardiogenic shock after myocardial infarction, to
      those with chronic decompensated heart failure. For patients requiring
      biventricular support, we have used a hybrid system consisting of a HeartMate II
      LVAD and CentriMag right ventricular assist device (RVAD). The purpose of this
      study was to determine the 1-year survival in patients requiring isolated LVAD
      and patients requiring biventricular support. METHODS: All patients who underwent
      HeartMate II LVAD alone or in conjunction with a temporary CentriMag RVAD were
      examined from 2006 to 2011. Preoperative demographics, operative outcomes, and
      survival were analyzed. RESULTS: A total of 139 patients required HeartMate II
      insertion; 34 (24%) required biventricular support at the time of HeartMate II
      implantation. The mean duration of biventricular support was 17 +/- 11.9 days
      (range, 6 to 56 days) with 91.8% (n = 31) of RVADs successfully explanted.
      Survival to hospital discharge was not different between groups (95.2 versus
      88.2%; p = 0.2). However, 1-year survival was significantly greater in patients
      who required isolated HeartMate II LVAD (87% versus 77%; p = 0.03). CONCLUSIONS:
      Biventricular support using a HeartMate II LVAD and CentriMag RVAD resulted in
      limited mortality at hospital discharge. However biventricular dysfunction does
      not have a favorable outcome at 1 year when compared with patients requiring
      isolated HeartMate II.

PMID- 24035304
TI  - Minimally invasive mitral valve surgery: influence of aortic clamping technique
      on early outcomes.
AB  - BACKGROUND: Several methods of aortic clamping have been described for minimally
      invasive mitral valve surgery (MIMVS). The aim of this study was to compare the
      endoaortic balloon occlusion technique with the transthoracic clamp approach in
      terms of perioperative outcomes. METHODS: Between May 2006 and October 2011, a
      total of 259 patients underwent MIMVS through a 4 to 5 cm right anterolateral
      minithoracotomy. In 243 (93.8%) of these, the aorta was clamped using either the
      endoaortic balloon occlusion technique (endoballoon, n = 140) or the
      transthoracic clamp technique (transthoracic, n = 103). RESULTS: Patients in the
      endoballoon group had significantly longer operating time (4.3 +/- 1.0 hours vs
      3.2 +/- 0.8 hours, p < 0.001), cardiopulmonary bypass time (143 +/- 44 minutes vs
      111 +/- 29 minutes , p < 0.001), and cross-clamp time (114 +/- 38 minutes vs 86
      +/- 23 minutes , p < 0.001). Perioperative blood loss was higher in the
      endoballoon group (287 +/- 239 mL vs 213 +/- 189 mL, p = 0.008) as was the mean
      postoperative creatinine kinase-MB level (36 +/- 44 MUg/L vs 26 +/- 12 MUg/L, p =
      0.011). The repair rate was 99% or greater in both groups (p = 0.99). All
      patients left the operating room with no or trivial residual mitral regurgitation
      on transesophageal echocardiographic evaluation. In the endoballoon group there
      was 1 stroke (1%) and 5 myocardial infarctions (4%), compared with 2 strokes (2%)
      in the transthoracic group (p = not significant). There were 4 cases of
      postoperative cardiogenic shock, all of which occurred in the endoballoon group
      (p = 0.14). In-hospital mortality occurred in 2 patients from each group (p =
      0.99). CONCLUSIONS: Minimally invasive mitral valve surgery can be performed
      successfully using either the endoaortic balloon technique or the transthoracic
      clamp approach. However, the transthoracic technique results in shorter operation
      time, less perioperative bleeding and better myocardial protection.

PMID- 24035306
TI  - Surgical proficiency and quality indicators in off-pump coronary artery bypass.
AB  - BACKGROUND: Off-pump coronary artery bypass (OPCAB) was developed to decrease
      postoperative mortality and morbidity. Surgeon experience influences outcome. The
      required levels of surgical proficiency and maturation of technical skills are
      uncertain. We sought to assess the surgical proficiency in OPCAB and to identify
      the required levels of technical maturation. METHODS: We included 1,055
      consecutive patients undergoing OPCAB. Patients were divided by 100s into 11
      groups by timing of operation. Surgical proficiency was evaluated by 2 quality
      indicators: revascularization index and conversion rate in nonemergency cases.
      RESULTS: Mode of intervention was elective in 768 patients, urgent in 185
      patients, and emergent in 102 patients (9.7%). The in-hospital mortality rate was
      5.1% and ranged from 3% (group 3) to 9% (group 11). The percentage of triple
      vessel disease and the mean number of diseased vessels increased over time. The
      mean number of distal anastomoses increased over time, from 2.64 +/- 0.82 in
      group 1 to 4.13 +/- 0.98 in group 11. It reached a plateau of 4.0 at group 7
      (cases 600-700). The revascularization index also increased over time, from 1.01
      +/- 0.20 in group 1 to 1.41 +/- 0.28 in group 11. It reached a plateau of 1.4 at
      group 7 (cases 600-700). The conversion rate in nonemergent cases decreased
      rapidly as the volume of OPCAB increased, and it reached a baseline of 5% at
      group 3 (cases 200-300). CONCLUSIONS: Surgical proficiency at performing OPCAB
      could be evaluated with 2 quality indicators: revascularization index of 1.4 or
      more and conversion rate in nonemergent cases of 5% or less. The required case
      number for technical maturation was 200 to 300 for conversion and 600 to 700 for
      complete revascularization.

PMID- 24035305
TI  - Total muscle-sparing uniportal video-assisted thoracoscopic surgery lobectomy.
AB  - BACKGROUND: Conventional video-assisted thoracoscopic lobectomy uses multiple
      incisions, including an access incision and several port incisions. This series
      aims to evaluate the technical feasibility and early results of uniportal video
      assisted thoracoscopic surgery (UVATS) lobectomy using a small, total muscle
      sparing incision. METHODS: We performed the first UVATS lobectomy in June 2009,
      and 38 major resections were attempted using this approach until September 2011.
      A single, small, muscle-sparing incision was made without rib spreading. True
      anatomic hilar dissection, individual vascular and bronchial ligation, and
      mediastinal lymph node dissection were performed under thoracoscopic
      visualization on a monitor. RESULTS: Thirty-two patients (84%) had malignant
      diseases, and 6 patients (16%) had benign diseases. Of the primary lung cancers,
      85% were in stage I. Of the 38 attempted major resections, 32 UVATS lobectomies
      were successfully completed and 6 were converted to open thoracotomy. The early
      outcomes of successful UVATS lobectomy were analyzed (32 patients); 97% had no
      postoperative complications. There were no deaths. Mean pain score was 0.4 on
      postoperative day 1 and decreased to 0 by 1 week. Ninety-seven percent of
      patients received only oral analgesia postoperatively. Eight percent of patients
      experienced mild intercostal neuralgia not requiring treatment. No patients
      complained of shoulder dysfunction. The median duration of returning to full
      normal activities was 7 postoperative days. CONCLUSIONS: Total muscle-sparing
      UVATS lobectomy is technically feasible with low morbidity and mortality rates.
      Patients had minimal postoperative pain and narcotic use; and good functional
      outcomes with no shoulder dysfunction and early return to full normal activities.

PMID- 24035307
TI  - Evaluation of outcome and prognostic factors in thoracic primitive
      neuroectodermal tumor: a study of 84 cases.
AB  - BACKGROUND: Data on thoracic primitive neuroectodermal tumor (PNET) treated with
      a uniform chemotherapy protocol are minimal in the literature. We analyzed
      patients with thoracic PNET for outcome and prognostic factors. METHODS: This is
      a single-institutional data review of patients treated between June 2003 and
      November 2011 with uniform neoadjuvant chemotherapy, surgical intervention, or
      radiotherapy (RT), or a combination of these treatments as local therapy followed
      by adjuvant chemotherapy. RESULTS: Thoracic PNET was found in 84 of 374 (22%)
      patients with PNET with a median age of 15 years (range, 3-40 years); 27 (32%) of
      these patients had metastases. Thirty patients underwent surgical resection; 27
      patients received radical RT after neoadjuvant chemotherapy. The radical RT group
      did not have adverse tumor characteristics or poor response to neoadjuvant
      chemotherapy. At median follow-up of 20.8 months (range, 2-104.6 months), 5-year
      event-free survival (EFS), overall survival (OS), and local control rate (LCR)
      were 24.4% +/- 5.9%, 47.9% +/- 8.4%, and 59.3% +/- 9%, respectively, for the
      entire cohort, and 31% +/- 7.7%, 59% +/- 10.4%, and 67% +/- 9.7%, respectively,
      for the group with localized tumors. In multivariate analysis, symptom duration
      longer than 4 months (p = 0.03), primary tumor of skeletal origin (p = 0.03), and
      radical RT (p = 0.006) predicted inferior EFS in the entire cohort and those with
      localized disease; metastatic disease (p = 0.002) predicted inferior OS. Radical
      RT predicted inferior LCR in the entire cohort and the group with localized
      tumor; tumor diameter larger than 8 cm (p = 0.02) and symptom duration longer
      than 4 months (p = 0.02) predicted inferior LCR in the group with localized
      tumor. CONCLUSIONS: This is a single-institutional experience of 84 patients with
      thoracic PNETs who underwent a uniform chemotherapy protocol. Novel prognostic
      factors were identified for thoracic PNET. All efforts should be made to resect
      primary tumor after neoadjuvant chemotherapy because radical RT results in
      inferior EFS and LCR despite good response to neoadjuvant chemotherapy.

PMID- 24035308
TI  - Disclosure of physician-specific behavior improves blood utilization protocol
      adherence in cardiac surgery.
AB  - BACKGROUND: Evidence indicates that a transfusion (Tx) trigger hemoglobin (Hgb)
      value of 8 gm/dL may be safer than a more liberal Tx trigger in cardiac surgery
      (CS) patients. We hypothesized that weekly physician feedback would improve
      adherence to such a protocol, but that the public identification of individual
      physician behavior would have an additive effect. METHODS: We concurrently
      reviewed all adult CS patients at our institution from December 1, 2010 to May
      27, 2011. We matched any cardiac surgery intensive care unit Tx event (red blood
      cells) with the Hgb value immediately before Tx. Patients requiring massive
      transfusions (>10 units/24 hours) were excluded. After all providers agreed upon
      a Hgb of 8 as the Tx trigger, we studied 3 consecutive time periods: no feedback,
      weekly feedback of group Tx behavior, and weekly feedback with identification of
      individual surgeon Tx behavior. RESULTS: Of the 512 patients who underwent
      cardiac operations, 144 patients underwent 510 Tx events. Compared with period 1,
      the unadjusted odds of receiving a Tx above 8 gm/dL decreased by 48% in study
      period 2(odds ratio: 0.52, p < 0.01), and 63% in study period 3(odds ratio: 0.37,
      p <0.001). Single unit transfusion rates increased from 77% to greater than 90%
      (p < 0.001). In-hospital mortality also fell from period 1 to period 3 (7.0% to
      1.5%, p = 0.02) with the observed to expected mortality ratio decreasing from
      2.19 to 0.51. CONCLUSIONS: Blood transfusion protocol adherence improves when
      weekly feedback is provided. Identifying individual surgeon behavior improves
      adherence to a greater degree. Routine presentation of quality metrics with
      identification of individual physician-specific behavior may be the most
      effective way to accomplish performance improvement.

PMID- 24035309
TI  - Developmental programming of growth: genetic variant in GH2 gene encoding
      placental growth hormone contributes to adult height determination.
AB  - INTRODUCTION: Given the physiological role of placental growth hormone (PGH)
      during intrauterine development and growth, genetic variation in the coding
      Growth hormone 2 (GH2) gene may modulate developmental programming of adult
      stature. Two major GH2 variants were described worldwide, determined by single
      polymorphism (rs2006123; c.171 + 50C > A). We sought to study whether GH2
      variants may contribute to adult anthropometric measurements. METHODS: Genotyping
      of GH2 SNP rs2006123 by RFLP, testing its genetic association with adult height
      and Body Mass Index (BMI) by linear regression analysis, and combining the
      results of three individual study samples in meta-analysis. STUDY SAMPLES: HYPEST
      (Estonia), n = 1464 (506 men/958 women), CADCZ (Czech), n = 871 (518/353); UFA
      (Bashkortostan), n = 954 (655/299); meta-analysis, n = 3289 (1679/1610). RESULTS:
      Meta-analysis across HYPEST, CADCZ and UFA samples (n = 3289) resulted in
      significant association of GH2 rs2006123 with height (recessive model: AA
      homozygote effect: beta (SE) = 1.26 (0.46), P = 5.90 * 10-3; additive model: A
      allele effect: beta (SE) = 0.45 (0.18), P = 1.40 * 10-2). Among men (n = 1679),
      the association of the A-allele with taller stature remained significant after
      multiple-testing correction (additive effect: beta = 0.86 (0.28), P = 1.83 * 10
      3). No association was detected with BMI. Notably, rs2006123 was in strong LD (r2
      >= 0.87) with SNPs significantly associated with height (rs2665838, rs7209435,
      rs11658329) and mapped near GH2 in three independent meta-analyses of GWA
      studies. CONCLUSIONS: This is the first study demonstrating a link between a
      placental gene variant and programming of growth potential in adulthood. The
      detected association between PGH encoding GH2 and adult height promotes further
      research on the role of placental genes in prenatal programming of human
      metabolism.

PMID- 24035310
TI  - Body-related state shame and guilt in women: do causal attributions mediate the
      influence of physical self-concept and shame and guilt proneness.
AB  - Guided by the process model of self-conscious emotions, this study examined
      whether physical self-concept (PSC) and shame and guilt proneness were associated
      with body-related self-conscious emotions of state shame and guilt and if these
      relationships were mediated by attributions of stability, globality, and
      controllability. Female participants (N=284; Mean age=20.6+/-1.9 years) completed
      measures of PSC and shame and guilt proneness before reading a hypothetical
      scenario. Participants completed measures of attributions and state shame and
      guilt in response to the scenario. Significant relationships were noted between
      state shame and attributions of globality and controllability, and shame
      proneness, guilt proneness, and PSC. Similar relationships, with the additional
      predictor of stability, were found for state guilt. Mediation analysis partially
      supported the process model hypotheses for shame. Results indicate PSC and shame
      proneness are important in predicting body-related emotions, but the role of
      specific attributions are still unclear. 

PMID- 24035311
TI  - Use of anti-malarial drugs and the risk of developing eye disorders.
AB  - BACKGROUND: Ocular toxicity was described in the late 1950s for some anti
      malarial drugs, but only limited information is available on the comparison of
      ocular toxicity of different anti-malarials. METHODS: We conducted a follow-up
      study with a nested case-control analysis using the General Practice Research
      Database to compare the risk of developing a first-time diagnosis of an eye
      disorder during exposure of mefloquine, chloroquine and/or proguanil or
      atovaquone/proguanil use to non-users. We calculated incidence rates with 95%
      confidence intervals (CI) and odds ratios using multivariate conditional logistic
      regression analyses. RESULTS: We included 83,148 patients and identified 652
      cases with an incident eye disorder. The incidence rates with 95% CI of all eye
      disorders combined in users of mefloquine, chloroquine and/or proguanil,
      atovaquone/proguanil or travellers not using anti-malarials were 5.3 (4.3-6.5),
      7.1 (5.0-9.9), 6.3 (5.6-7.2) and 5.1 (4.6-5.7), per 1000 person-years,
      respectively. As compared to non-users of anti-malarials, the adjusted odds ratio
      with 95% CI in the nested case-control analysis for users of mefloquine,
      chloroquine and/or proguanil, or atovaquone/proguanil were 1.33 (1.01-1.75), 1.61
      (1.06-2.45), and 1.25 (1.03-1.52), respectively. CONCLUSIONS: The study provides
      evidence that there was an increased risk of eye disorders in users of all anti
      malarials compared to non-users of anti-malarials.

PMID- 24035312
TI  - Assessment and instruction to promote higher order thinking in nursing students.
AB  - OBJECTIVES: The dearth of data on the role of assessment in higher education
      formed the two purposes of this study: first, to explore assessment strategies
      commonly used in nursing education by analyzing the curriculum documents of three
      baccalaureate nursing programs in Lebanon against Bloom's Taxonomy of learning,
      and second to unravel issues of instruction and assessment by categorizing data
      into teacher- and learner-centered strategies. DESIGN: Content analysis research
      technique applied to analyze the curriculum documents of three baccalaureate
      nursing programs in Beirut, Lebanon. METHOD: After obtaining IRB approval and
      consent to access the curriculum documents of the programs, data were analyzed
      using the content analysis research technique. Data on assessments and
      instruction were categorized into student-centered and teacher-centered.
      FINDINGS: Data revealed deficiency in employing learner-centered strategies in
      the assessment and instruction of the three programs. There was evidence that
      educators of the programs focus on teaching content and examining retention, thus
      supporting prior notions on teaching to the test and accusations in earnest on
      adherence to the traditional and behavioral curriculum perspectives. Such
      curricula leave little room for the development of higher order thinking in
      learners. CONCLUSIONS: Although assessments are believed to be indicators of
      program and teaching effectiveness, there is relatively alarming information on
      the incompatibility between current assessment practices and demands of the
      workplace. There is an urgent need for transforming educators' beliefs,
      knowledge, and skills on testing, since teaching to pass a test could impede
      knowledge transfer and deter the development of learners' higher order thinking
      skills.

PMID- 24035313
TI  - Discriminating dominant computed tomography phenotypes in smokers without or with
      mild COPD.
AB  - BACKGROUND: Finding phenotypes within COPD patients may prove imperative for
      optimizing treatment and prognosis. We hypothesized that it would be possible to
      discriminate emphysematous, large airway wall thickening and small airways
      disease dominant phenotypes. METHODS: Inspiratory and expiratory CTs were
      performed in 1140 male smokers without or with mild COPD to quantify emphysema,
      airway wall thickness and air trapping. Spirometry, residual volume to total lung
      capacity (RV/TLC) and diffusion capacity (Kco) were measured. Dominant phenotype
      (emphysema, airway wall thickening or air trapping dominant) was defined as one
      of the respective CT measure in the upper quartile, with the other measures not
      in the upper quartile. RESULTS: 573 subjects had any of the three CT measures in
      the upper quartile. Of these, 367 (64%) were in a single dominant group and 206
      (36%) were in a mixed group. Airway wall thickening dominance was associated with
      younger age (p < 0.001), higher body mass index (p < 0.001), more wheezing (p <
      0.05) and lower FEV1 %predicted (p < 0.001). Emphysema dominant subjects had
      lower FEV1/FVC (p < 0.05) and Kco %predicted (p < 0.05). There was no significant
      difference in respiratory related hospitalizations (p = 0.09). CONCLUSION: CT
      measures can discriminate three different CT dominant groups of disease in male
      smokers without or with mild COPD. TRIAL REGISTRATION NUMBER: ISRCTN63545820,
      registered at www.trialregister.nl.

PMID- 24035314
TI  - RNA silencing targeting PIN (protein inhibitor of neuronal nitric oxide synthase)
      attenuates the development of hypertension in young spontaneously hypertensive
      rats.
AB  - Nitric oxide (NO) deficiency contributes to hypertension. We previously showed
      that neuronal nitric oxide synthase (nNOS) was involved in hypertension and
      kidney damage in spontaneously hypertensive rats (SHRs). The protein inhibitor of
      nNOS (PIN) has been reported to inhibit activity of nNOS.Thus, we tested whether
      increased PIN in the kidney results in hypertension and whether small interfering
      RNA (siRNA) targeting PIN attenuates hypertension in SHRs. Four-week-old male
      SHRs were assigned into three groups (n = 6-7/group): SHR; SHR + PIN, SHR that
      received siRNA targeting PIN; and SHR + NC, SHR treated with random negative
      control siRNA. Rats were sacrificed at 12 weeks of age. PIN protein expression
      was inhibited considerably when PIN siRNA was transfected into NRK52E cells (90%
      siRNA at 1 nM). The increases of BP were attenuated by siRNA targeting PIN in 12
      week-old SHRs. Immunostaining of nNOS-alpha and total nNOS was greater in SHR +
      PIN group than SHR. Moreover, renal superoxide production and 8
      hydroxydeoxyguanosine (8-OHdG) staining were more decreased in the SHR + PIN
      group than SHRs. We conclude that PIN siRNA reduced PIN expression in vitro and
      in vivo. PIN siRNA therapy attenuates hypertension in SHRs at 12 weeks of age.
      Our results suggest that PIN is involved in the development of hypertension.

PMID- 24035315
TI  - Apparent and true resistant hypertension: why not the same?

PMID- 24035317
TI  - Age cutoff for the loss of survival benefit from use of radial artery in coronary
      artery bypass grafting.
AB  - BACKGROUND: Controversy still exists about the superiority of the radial artery
      (RA) over the saphenous vein graft (SVG) as a second conduit for surgical
      myocardial revascularization. We aimed to investigate the presence of any
      survival benefit from use of the RA and relate it to patients' age. METHODS:
      Propensity score matching was conducted on 9005 patients who underwent first-time
      isolated coronary artery bypass grafting (CABG) using the left internal thoracic
      artery at a single institution from 1996 to 2012. The use of RA was recorded in
      936 patients, whereas the use of SVGs only was recorded in 8069 patients. The
      primary study end point was all-cause death. The interaction between patients'
      age and any survival benefit from the RA was assessed by spline analysis.
      RESULTS: After propensity matching, the sample size consisted of 809 matched
      pairs. In the matched group, mean follow-up was 6.4 +/- 3.6 years (range, 0-13.6
      years). Survival was 96.8% +/- 0.6% versus 96.0% +/- 0.6% at 1 year, 91.4% +/-
      1.1% versus 90.1% +/- 1.0% at 5 years, and 83.2% +/- 1.7% versus 79.4% +/- 1.9%
      at 10 years for patients receiving RA or SVG, respectively. RA use was associated
      with a lower risk for late death (hazard ratio [HR], 0.75; 95% confidence
      interval [CI], 0.57-0.98; P = .03). However, the protective effect from RA on
      late survival was not equally present across all age groups, as shown by spline
      analysis. The survival advantage from RA was maximum in patients 60 years and
      younger (upper limit of 95% CI, <1) and gradually declined with increasing age,
      until it was no longer present in patients older than 70 years (adjusted HR,
      0.90; 95% CI, 0.63-1.28; P = .57). CONCLUSIONS: The use of the radial artery
      graft as a second conduit improves all-cause mortality in patients undergoing
      primary isolated CABG up to the age of 70 years.

PMID- 24035319
TI  - Discussion.

PMID- 24035318
TI  - Technical Performance Scores are strongly associated with early mortality,
      postoperative adverse events, and intensive care unit length of stay-analysis of
      consecutive discharges for 2 years.
AB  - OBJECTIVES: Previous work in our institution has indicated that the Technical
      Performance Score (TPS) is highly associated with early outcomes in select
      subsets of procedures and age groups. We hypothesized that the TPS could predict
      early outcomes in a wide range of diagnoses and age groups. METHODS: Consecutive
      patients discharged from January 2011 to March 2013 were prospectively evaluated.
      The TPS was assigned according to the discharge echocardiographic findings and
      the need for reinterventions in the anatomic area of interest. Case complexity
      was determined using Risk Adjustment for Congenital Heart Surgery (RACHS-1)
      categories. Early mortality and postoperative adverse events were recorded.
      Relationships between the TPS and outcomes were assessed after adjusting for the
      baseline patient characteristics. RESULTS: The median age of the 1926 patients
      was 1.8 years (range, 0 days to 68 years). Bypass was used in 1740 (90%); 322
      (17%) were neonates, 520 (27%) infants, 873 (45%) children, 211 (11%) adults. TPS
      was class 1 (optimal) in 956 (50%), class 2 (adequate) in 584 (30%), and class 3
      (inadequate) in 226 (12%); 160 patients (8%) could not be scored. A total of 51
      early deaths (2.6%) and 111 adverse events (5.7%) occurred. On univariate
      analysis, age, RACHS-1 category, and TPS were significantly associated with
      mortality and the occurrence of adverse events. On multivariate modeling, class 3
      (inadequate) TPS was strongly associated with mortality (odds ratio, 16.9; 95%
      confidence interval, 6.7-42.9; P < .001), adverse events (odds ratio, 6.9; 95%
      confidence interval, 4.1-11.6; P < .001), and postoperative intensive care unit
      length of stay (coefficient, 2.3; 95% confidence interval, 2.0-2.6; P < .001)
      after adjusting for other covariates. CONCLUSIONS: The TPS is strongly associated
      with early outcomes across a wide range of ages and disease complexity and can
      serve as important tool for self-assessment and quality improvement.

PMID- 24035320
TI  - Novel treatment for critical aortic stenosis with severe aortic root
      calcification and coronary disease: combined left internal thoracic artery graft
      to left anterior descending coronary artery and deployment of transcatheter
      aortic valve implantation valve under direct vision.

PMID- 24035321
TI  - Idiopathic urinary findings and fetal growth restriction in low risk pregnancy.
AB  - OBJECTIVE: To determine whether maternal urinary findings in the first trimester
      of pregnancy are associated with fetal growth restriction. STUDY DESIGN: The
      prevalence of urinary findings in singleton pregnancies complicated by fetal
      growth restriction were compared with a low-risk control group of pregnancies who
      gave birth to normal weight babies, in the same condition. RESULTS: There were
      significant statistical differences in the mean gestational age (p < 0.001),
      isolated asymptomatic bacteriuria (p<0.001), hematuria (p = 0.002, OR = 6.6, CI =
      1.8-24.2) and proteinuria (p = 0.016, OR = 4.1, CI = 1.2-13.3). There was no
      recognizable relation between ketonuria and fetal growth restriction. CONCLUSION:
      Our data showed a relation between the increase of adverse pregnancy outcomes,
      including fetal growth restriction, and hematuria, proteinuria and asymptomatic
      bacteriuria. Appropriate monitoring of pregnant women using these findings may be
      helpful in the identification of more complications.

PMID- 24035322
TI  - Cost-effectiveness analysis of the surgical treatment of female urinary
      incontinence using slings and meshes.
AB  - OBJECTIVE: To determine the cost-utility and cost-effectiveness of the surgical
      treatment of female urinary incontinence using suburethral slings and prolapse
      meshes compared with therapeutic abstention. STUDY DESIGN: An economic analysis
      was performed on 69 women receiving surgical treatment for urinary incontinence
      using suburethral slings and prolapse meshes. To calculate the procedure's cost
      effectiveness, an incremental analysis up to one year was performed using the
      incremental cost-effectiveness ratio (ICER). The costs were calculated using a
      cost-by-process model. Answers to the health-related quality of life
      questionnaires EQ-5D (generic) and International Consultation Incontinence
      Questionnaire Short-form (specific) were collected before the operation and as
      well as one month and one year post-operation to calculate the utility, using
      quality-adjusted life years (QALY), and the effectiveness, respectively. To
      complete the economic evaluation, we derived confidence ellipses and
      acceptability curves. The analysis was conducted for the entire sample and also
      for each type of urinary incontinence. RESULTS: In total, 45 women presented with
      stress incontinence, 15 with mixed incontinence and 9 with incontinence
      associated with prolapse. The average cost per patient at one year post-operation
      was 1220 ?. The QALY achieved at one year was 0.046. The results reveal an ICER
      at one year of 26,288 ?/QALY, which is below the cost-effectiveness threshold
      considered acceptable, and this value was lower for stress incontinence (21,191
      ?/QALY). The cost-effectiveness was 106.5 ?/International Consultation
      Incontinence Questionnaire Short-form unit. CONCLUSION: Surgery for female
      urinary incontinence using slings is cost-effective compared with abstention in
      our public health environment.

PMID- 24035323
TI  - Placental growth factor and soluble fms-like tyrosine kinase-1 are useful markers
      for the prediction of preeclampsia but not for small for gestational age
      neonates: a longitudinal study.
AB  - OBJECTIVE: To determine maternal serum concentrations of placental growth factor
      (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal
      pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver
      a small for gestational age (SGA) infant, in order to evaluate them as markers
      for the prediction of preeclampsia. STUDY DESIGN: In this case-control study we
      included 12 singleton pregnancies that developed preeclampsia and 104 randomly
      selected singleton normal pregnancies. Fourteen of the normal pregnancies gave
      birth to an SGA infant. Blood samples and ultrasonographic data were collected
      during the 1st, 2nd and 3rd trimesters of pregnancy. RESULTS: In preeclamptic
      pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower
      in the 2nd (208; 84-339) (p=0.035) and in the 3rd trimester (202; 109-284)
      (p=0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521;
      2101-3041) (p=0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF
      3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA
      infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in
      any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic
      pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The
      relative difference and the slope of PlGF concentration between 1st and 2nd
      trimester were significantly reduced in preeclampsia compared to normal
      pregnancies. A logistic regression model with predictors BMI, 2nd trimester
      Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave
      46% sensitivity and 99% specificity for the prediction of preeclampsia, with a
      very high negative predictive value of 98.3%. CONCLUSIONS: Our study confirms
      that maternal serum PlGF concentration is significantly lower, at least after
      20th week, while sFlt-1 concentration is significantly higher in 3rd trimester,
      in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to
      SGA infants do not have altered angiogenic factor concentrations throughout
      pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester,
      uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful
      markers for the prediction of preeclampsia.

PMID- 24035324
TI  - Measurement of uterine fibroid volume: a comparative accuracy and validation of
      methods study.
AB  - OBJECTIVE: A range of measurement techniques have been described which may be
      used to calculate uterine fibroid volume. A commonly-reported method involves
      application of a formula for the volume of an ellipsoid sphere to three
      orthogonal axes of a fibroid as measured on cross-sectional images. We aimed to
      compare this method and a second method, that of software-computed parallel
      planimetric uterine fibroid computation on MRI images, to a gold standard: the
      volume of objects measured by water displacement. We also compared these methods
      in volume estimation of patient fibroids using MRI data. STUDY DESIGN: Mixed
      observational study and blinded cross-sectional analysis of imaging data.
      RESULTS: Large inter-observer variability was noted when using the ellipsoid
      formula method, which was also inaccurate when compared to the gold standard.
      Conversely, the parallel planimetric method showed excellent interobserver
      correlation and a high degree of correlation with gold standard volume
      measurements. CONCLUSION: We conclude that the parallel planimetric method,
      although a more complex and time consuming technique, is the more accurate and
      therefore preferred method for measuring uterine fibroid volume.

PMID- 24035325
TI  - Is transcatheter closure better than medical therapy for cryptogenic stroke with
      patent foramen ovale? A meta-analysis of randomised trials.
AB  - INTRODUCTION: The prevalence of patent foramen ovale among patients with
      cryptogenic stroke is higher than that in the general population. Closure with a
      percutaneous device is often recommended in such patients, but it is not known
      whether this intervention reduces the risk of recurrent stroke. METHODS: A
      systematic search was conducted using MEDLINE, PubMed, EMBASE, Current Contents
      Connect, Cochrane library, Google Scholar, Science Direct, and Web of Science.
      Original data were abstracted from each study and used to calculate a pooled
      event rate (ER), odd ratio (OR) and 95% confidence interval (95% CI). RESULTS:
      Only three randomised trials comprising 2303 patients met full criteria for
      analysis. Procedural success (ER: 94.20%, 95% CI: 87.6-97.4%) and effective
      closure (ER: 92.70%, 95% CI: 85.9-96.4%) of closure therapy were good. The odds
      ratio for stroke (OR: 0.654, 95% CI: 0.358-1.193) and transient ischaemic attack
      (OR: 0.768, 95% CI: 0.413-1.429) did not confer a benefit of PFO closure over
      medical therapy. Age {<45 years (OR: 0.449, 95% CI: 0.117-1.722), >45 years (OR:
      0.707, 95% CI: 0.27-1.856)}, gender {males (OR: 0.498, 95% CI: 0.247-1.004),
      females (OR: 1.16, 95% CI: 0.597-2.255)}, substantial shunt size (OR: 0.354, 95%
      CI: 0.089-1.406) and the presence of atrial septal aneurysm (OR: 0.7, 95% CI:
      0.21-2.33) did not influence the treatment effect of PFO closure. However, the
      adverse events like major vascular complication (OR: 10.905, 95% CI: 1.997
      59.562) and atrial fibrillation (OR: 3.297, 95% CI: 0.874-12.432) were
      significantly higher in the closure group. CONCLUSIONS: In patients with
      cryptogenic stroke or TIA who had a patent foramen ovale, closure with a device
      does not confer an advantage over medical therapy and is associated with adverse
      events like major vascular complication and atrial fibrillation.

PMID- 24035326
TI  - Iodine supplementation during pregnancy and lactation. Position statement of the
      working group on disorders related to iodine deficiency and thyroid dysfunction
      of the Spanish Society of Endocrinology and Nutrition.
AB  - Severe and mild iodine deficiency during pregnancy and lactation affects thyroid
      function of the mother and neonate as well as the infant's neuropsychological
      development. Studies performed in Spain confirm that most women are iodine
      deficient during pregnancy and lactation. Pregnant and breast feeding women and
      women planning to become pregnant should take iodine supplements. 

PMID- 24035327
TI  - Anal carcinoma: impact of TN category of disease on survival, disease relapse,
      and colostomy failure in US Gastrointestinal Intergroup RTOG 98-11 phase 3 trial.
AB  - PURPOSE: The long-term update of US GI Intergroup RTOG 98-11 anal cancer trial
      found that concurrent chemoradiation (CCRT) with fluorouracil (5-FU) plus
      mitomycin had a significant impact on disease-free survival (DFS) and overall
      survival (OS) compared with induction plus concurrent 5-FU plus cisplatin. The
      intent of the current analysis was to determine the impact of tumor node (TN)
      category of disease on survival (DFS and OS), colostomy failure (CF), and relapse
      (local-regional failure [LRF] and distant metastases [DM]) in this patient group.
      METHODS AND MATERIALS: DFS and OS were estimated univariately by using the Kaplan
      Meier method, and 6 TN categories were compared by the log-rank test (T2N0, T3N0,
      T4N0, T2N1-3, T3N1-3, and T4N1-3). Time to relapse and colostomy were estimated
      by the cumulative incidence method, and TN categories were compared using Gray's
      test. RESULTS: Of 682 patients, 620 were analyzable for outcomes by TN category.
      All endpoints showed statistically significant differences among the TN
      categories of disease (OS, P<.0001; DFS, P<.0001; LRF, P<.0001; DM, P=.0011; CF,
      P=.01). Patients with the poorest OS, DFS, and LRF outcomes were those with T3-4N
      positive (+) disease. CF was lowest for T2N0 and T2N+ (11%, 11%, respectively)
      and worst for the T4N0, T3N+, and T4N+ categories (26%, 27%, 24%, respectively).
      CONCLUSIONS: TN category of disease has a statistically significant impact on OS,
      DFS, LRF, DM, and CF in patients treated with CCRT and provides excellent
      prognostic information for outcomes in patients with anal carcinoma. Significant
      challenges remain for patients with T4N0 and T3-4N+ categories of disease with
      regard to survival, relapse, and CF and lesser challenges for T2-3N0/T2N+
      categories.

PMID- 24035328
TI  - Parotid glands dose-effect relationships based on their actually delivered doses:
      implications for adaptive replanning in radiation therapy of head-and-neck
      cancer.
AB  - PURPOSE: Doses actually delivered to the parotid glands during radiation therapy
      often exceed planned doses. We hypothesized that the delivered doses correlate
      better with parotid salivary output than the planned doses, used in all previous
      studies, and that determining these correlations will help make decisions
      regarding adaptive radiation therapy (ART) aimed at reducing the delivered doses.
      METHODS AND MATERIALS: In this prospective study, oropharyngeal cancer patients
      treated definitively with chemoirradiation underwent daily cone-beam computed
      tomography (CBCT) with clinical setup alignment based on the C2 posterior edge.
      Parotid glands in the CBCTs were aligned by deformable registration to calculate
      cumulative delivered doses. Stimulated salivary flow rates were measured
      separately from each parotid gland pretherapy and periodically posttherapy.
      RESULTS: Thirty-six parotid glands of 18 patients were analyzed. Average mean
      planned doses was 32 Gy, and differences from planned to delivered mean gland
      doses were -4.9 to +8.4 Gy, median difference +2.2 Gy in glands in which
      delivered doses increased relative to planned. Both planned and delivered mean
      doses were significantly correlated with posttreatment salivary outputs at almost
      all posttherapy time points, without statistically significant differences in the
      correlations. Large dispersions (on average, SD 3.6 Gy) characterized the dose
      effect relationships for both. The differences between the cumulative delivered
      doses and planned doses were evident at first fraction (r=.92, P<.0001) because
      of complex setup deviations (eg, rotations and neck articulations), uncorrected
      by the translational clinical alignments. CONCLUSIONS: After daily translational
      setup corrections, differences between planned and delivered doses in most glands
      were small relative to the SDs of the dose-saliva data, suggesting that ART is
      not likely to gain measurable salivary output improvement in most cases. These
      differences were observed at first treatment, indicating potential benefit for
      more complex setup corrections or adaptive interventions in the minority of
      patients with large deviations detected early by CBCT.

PMID- 24035329
TI  - Predicting esophagitis after chemoradiation therapy for non-small cell lung
      cancer: an individual patient data meta-analysis.
AB  - PURPOSE: Concurrent chemoradiation therapy (CCRT) improves survival compared with
      sequential treatment for locally advanced non-small cell lung cancer, but it
      increases toxicity, particularly radiation esophagitis (RE). Validated predictors
      of RE for clinical use are lacking. We performed an individual-patient-data meta
      analysis to determine factors predictive of clinically significant RE. METHODS
      AND MATERIALS: After a systematic review of the literature, data were obtained on
      1082 patients who underwent CCRT, including patients from Europe, North America,
      Asia, and Australia. Patients were randomly divided into training and validation
      sets (2/3 vs 1/3 of patients). Factors predictive of RE (grade>=2 and grade>=3)
      were assessed using logistic modeling, with the concordance statistic (c
      statistic) used to evaluate the performance of each model. RESULTS: The median
      radiation therapy dose delivered was 65 Gy, and the median follow-up time was 2.1
      years. Most patients (91%) received platinum-containing CCRT regimens. The
      development of RE was common, scored as grade 2 in 348 patients (32.2%), grade 3
      in 185 (17.1%), and grade 4 in 10 (0.9%). There were no RE-related deaths. On
      univariable analysis using the training set, several baseline factors were
      statistically predictive of RE (P<.05), but only dosimetric factors had good
      discrimination scores (c>.60). On multivariable analysis, the esophageal volume
      receiving >=60 Gy (V60) alone emerged as the best predictor of grade>=2 and
      grade>=3 RE, with good calibration and discrimination. Recursive partitioning
      identified 3 risk groups: low (V60<0.07%), intermediate (V60 0.07% to 16.99%),
      and high (V60>=17%). With use of the validation set, the predictive model
      performed inferiorly for the grade>=2 endpoint (c=.58) but performed well for the
      grade>=3 endpoint (c=.66). CONCLUSIONS: Clinically significant RE is common, but
      life-threatening complications occur in <1% of patients. Although several factors
      are statistically predictive of RE, the V60 alone provides the best predictive
      ability. Efforts to reduce the V60 should be prioritized, with further research
      needed to identify and validate new predictive factors.

PMID- 24035330
TI  - pN0(i+) breast cancer: treatment patterns, locoregional recurrence, and survival
      outcomes.
AB  - PURPOSE: To examine treatment patterns, recurrence, and survival outcomes in
      patients with pN0(i+) breast cancer. METHODS AND MATERIALS: Subjects were 5999
      women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between
      2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had
      pNmic (micrometastases>0.2 mm to <=2 mm), and 1212 (20%) had pN1a (1-3 positive
      macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier
      local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and
      overall survival were compared between nodal subgroups. Multivariable analysis
      was performed using Cox regression modeling. A 1:3 case-match analysis examined
      outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor
      and treatment characteristics. RESULTS: Median follow-up was 4.8 years. Adjuvant
      systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0,
      pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy
      (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in
      pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0
      versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20),
      RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR
      events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events
      in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+)
      was not associated with worse locoregional control or survival. On case-match
      analysis, LRR and overall survival were similar between pN0(i+) and matched pN0
      counterparts. CONCLUSIONS: Nodal involvement with isolated tumor cells is not a
      significant prognostic factor for LRR or survival in this study's multivariable
      and case-match analyses. These data do not support the routine use of nodal RT in
      the setting of pN0(i+) disease. Prospective studies are needed to define optimal
      locoregional management for women with pN0(i+) breast cancer.

PMID- 24035331
TI  - Impact of weight change during the course of concurrent chemoradiation therapy on
      outcomes in stage IIIB non-small cell lung cancer patients: retrospective
      analysis of 425 patients.
AB  - PURPOSE: We retrospectively investigated the impact of weight change (WC) during
      concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non
      small cell lung cancer (NSCLC) patients. METHODS AND MATERIALS: A total of 425
      patients treated with C-CRT were included. All patients received 60 to 66 Gy of
      thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based
      chemotherapy. Pre- and posttreatment weight measurements on first and last days
      of C-CRT were used for WC. Patients were divided into 2 groups: group 1=weight
      loss (WL); group 2=weight preservation/gain (WP) for comparative analyses.
      RESULTS: Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients
      (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow
      up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58
      (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%]
      for WL). Median overall survival (OS), locoregional progression-free survival
      (LRPFS), progression-free survival (PFS), and distant metastases-free survival
      (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months,
      respectively. Intergroup comparisons between WP and WL cohorts revealed
      significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each).
      On multivariate analyses, only WL and advanced T stage were associated with poor
      prognosis (P<.05). CONCLUSIONS: Present results in 425 stage 3B NSCLC patients
      demonstrated that WL during C-CRT is strongly associated with inferior survival
      outcomes compared to WP. This emerging finding might be useful by forming an
      encouraging basis for future investigations in facilitating a way to improve the
      outcomes of these patients experiencing WL during C-CRT.

PMID- 24035332
TI  - Hypoxia-independent downregulation of hypoxia-inducible factor 1 targets by
      androgen deprivation therapy in prostate cancer.
AB  - PURPOSE: We explored changes in hypoxia-inducible factor 1 (HIF1) signaling
      during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer
      xenografts under conditions in which no significant change in immunostaining of
      the hypoxia marker pimonidazole had occurred. METHODS AND MATERIALS: Gene
      expression profiles of volume-matched androgen-exposed and androgen-deprived
      CWR22 xenografts, with similar pimonidazole-positive fractions, were compared.
      Direct targets of androgen receptor (AR) and HIF1 transcription factors were
      identified among the differentially expressed genes by using published lists.
      Biological processes affected by ADT were determined by gene ontology analysis.
      HIF1alpha protein expression in xenografts and biopsy samples from 35 patients
      receiving neoadjuvant ADT was assessed by immunohistochemistry. RESULTS: A total
      of 1344 genes showed more than 2-fold change in expression by ADT, including 35
      downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR
      targets, and their downregulation was confirmed with quantitative RT-PCR.
      Significant suppression of the biological processes proliferation, metabolism,
      and stress response in androgen-deprived xenografts was found, consistent with
      tumor regression. Nineteen downregulated HIF1 targets were involved in those
      significant biological processes, most of them in metabolism. Four of these were
      shared AR and HIF1 targets, including genes encoding the regulatory glycolytic
      proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were
      induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming
      their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation
      of HIF1 targets was consistent with the absence of HIF1alpha protein in
      xenografts and downregulation in patients by ADT (P<.001). CONCLUSIONS: AR
      repression by ADT may lead to downregulation of HIF1 signaling independently of
      hypoxic fraction, and this may contribute to tumor regression. HIF1alpha
      expression is probably not a useful hypoxia biomarker during ADT in prostate
      cancer.

PMID- 24035333
TI  - Hyperbaric oxygen treatment in radiation-induced cystitis and proctitis: a
      prospective cohort study on patient-perceived quality of recovery.
AB  - PURPOSE: In this prospective cohort study, the effects of hyperbaric oxygen
      treatment (HBOT) were evaluated concerning patient-perceived symptoms of late
      radiation-induced cystitis and proctitis secondary to radiation therapy for
      pelvic cancer. METHODS AND MATERIALS: Thirty-nine patients, 35 men and 4 women
      with a mean age of 71 (range, 35-84) years were included after informed consent
      and institutional ethics approval. They had all been treated with radiation
      therapy for prostate (n=34), cervix (n=2), or rectal (n=3) cancer using external
      beam radiation at a dose of 25 to 75 Gy. Patients with hematuria requiring blood
      transfusion were excluded. The HBOT was delivered with 100% oxygen for 90 minutes
      at 2.0 to 2.4 atmospheres (ATA). Mean number of treatments was 36 (28-40).
      Symptoms were prospectively assessed using the Expanded Prostate Index Composite
      score before, during, and 6 to 12 months after HBOT. RESULTS: The HBOT was
      successfully conducted, and symptoms were alleviated in 76% for patients with
      radiation cystitis, 89% for patients with radiation proctitis, and 88% of
      patients with combined cystitis and proctitis. Symptom reduction was demonstrated
      by an increased Expanded Prostate Index Composite score in the urinary domain
      from 50+/-16 to 66+/-20 after treatment (P<.001) and in the bowel domain from
      48+/-18 to 68+/-18 after treatment (P<.001). For 31% of the patients with
      cystitis and 22% with proctitis, there were only trivial symptoms after HBOT. The
      improvement was sustained at follow-up in both domains 6 to 12 months after HBOT.
      No severe side effects were observed related to HBOT, and treatment compliance
      was high. CONCLUSIONS: HBOT can be an effective and safe treatment modality for
      late radiation therapy-induced soft tissue injuries in the pelvic region.

PMID- 24035334
TI  - Characterization of bone marrow mast cells in acute myeloid leukemia with t(8;21)
      (q22;q22); RUNX1-RUNX1T1.
AB  - Mast cells are often increased in AML with t(8;21). We analyzed characteristics
      of mast cells to elucidate their relationship with leukemic blasts. In 31 cases
      in which the results of KIT mutation analysis were available, five cases showed
      mutations. None of the cases positive for KIT mutation showed increased mast
      cells. In five cases with increased mast cells in which targeted-FISH analysis
      was performed for RUNX1-RUNX1T1, fusion signals demonstrated the translocation in
      mast cells in all cases. These findings confirm the shared origin between mast
      cells and leukemic blasts in AML with t(8;21). 

PMID- 24035335
TI  - Worlds apart? An exploration of prescribing and medicine-taking decisions by
      patients, GPs and local policy makers.
AB  - Current healthcare policy in the UK has been shaped by two major forces;
      increasing accountability to evidence-based standards and increasing patient
      involvement. Shared decision-making brings the patient into prescribing
      decisions, and guidelines introduce a third decision-maker, the policy maker,
      into the doctor-patient consultation. This study explored the decision-making
      processes used by patients and GPs in comparison to local policy makers. METHOD:
      Qualitative interviews with 8 GPs, 14 patients and 2 PCT Prescribing Advisers,
      followed by quantitative questionnaires completed by 305 GPs and 533 patients.
      RESULTS: Patients made individual medicine-taking decisions based on experience,
      personal financial and human cost, trust and the relational aspects of their
      interactions with doctors over time. In contrast local implementation of
      prescribing guidelines was based on consideration of financial costs, efficacy
      and risks, based on objective clinical evidence at a population level. GPs
      adopted a mid-position between these two polar views. Guidelines are written from
      a different perspective to the worldview of patients, and they tend to downplay
      the criteria most important to patients. This has the potential to have a harmful
      effect on patients' medicine-taking and adherence. Paradoxically, enforcing the
      use of guidelines could inhibit the achievement of guideline targets.

PMID- 24035336
TI  - WITHDRAWN: Design, synthesis and biological evaluation of 3-substituted-4
      anilinequinoline as EGFR tyrosine kinase inhibitors.

PMID- 24035337
TI  - 2-Amino-6-chloro-3,4-dihydroquinazoline: A novel 5-HT3 receptor antagonist with
      antidepressant character.
AB  - 2-Amino-6-chloro-3,4-dihydroquinazoline HCl (A6CDQ, 4) binds at 5-HT3 serotonin
      receptors and displays antidepressant-like action in the mouse tail suspension
      test (TST). Empirically, 4 was demonstrated to be a 5-HT3 receptor antagonist
      (two-electrode voltage clamp recordings using frog oocytes; IC50=0.26MUM), and
      one that should readily penetrate the blood-brain barrier (logP=1.86). 5-HT3
      receptor antagonists represent a potential approach to the development of new
      antidepressants, and 4 is an example of a structurally novel 5-HT3 receptor
      antagonist that is active in a preclinical antidepressant model (i.e., the mouse
      TST). 

PMID- 24035338
TI  - Discovery of 2,8-diazaspiro[4.5]decane-based trisubstituted urea derivatives as
      highly potent soluble epoxide hydrolase inhibitors and orally active drug
      candidates for treating hypertension.
AB  - We identified 2,8-diazaspiro[4.5]decane-based trisubstituted urea derivatives as
      highly potent soluble epoxide hydrolase (sEH) inhibitors and orally active agents
      for treating hypertension. Docking studies using human and murine sEH X-ray
      crystal structures revealed steric hindrance around the side chain of Phe406 of
      murine sEH. The trifluoromethyl moiety (11) was replaced with a trifluoromethoxy
      moiety (12) to prevent steric clash, and improved murine sEH inhibitory activity
      was observed. The oral administration of 12, 20, and 37 at a dose of 30mg/kg
      reduced blood pressure in spontaneously hypertensive rat, but had little effect
      on blood pressure in normotensive rat. 

PMID- 24035340
TI  - Synthesis of VS-105: A novel and potent vitamin D receptor agonist with reduced
      hypercalcemic effects.
AB  - We have synthesized a novel vitamin D receptor agonist VS-105 ((1R,3R)-5-((E)-2
      ((3alphaS,7alphaS)-1-((R)-1-((S)-3-hydroxy-2,3-dimethylbutoxy)ethyl)-7alpha
      methyldihydro-1H-inden-4(2H,5H,6H,7H,7alphaH)-ylidene)ethylidene)-2
      methylenecyclohexane-1,3-diol). Preparation of a-ring phenylphosphine oxide 11,
      followed by Wittig-Horner coupling of 11 with the protected 25-hydroxy
      Grundmann's ketone 22 generated the precursor 12. Deprotection of the TBDMS
      groups of 12 produced the target compound VS-105. The biological profiles of VS
      105 were evaluated using in vitro assays (VDR receptor binding, VDR reporter gene
      and HL-60 differentiation) in comparison to calcitriol (the endogenous hormone)
      or paricalcitol. Furthermore, the PTH suppressing potency and hypercalcemic side
      effects of VS-105 were evaluated in the 5/6 nephrectomized uremic rats in
      comparison to paricalcitol. Combining various changes at 20-epi, 22-oxa, 24
      methyl, and 2-methylene yielded VS-105 that not only is highly potent in inducing
      functional responses in vitro, but also effectively suppresses PTH in a dose
      range that does not affect serum calcium in the 5/6 nephrectomized uremic rats. 

PMID- 24035339
TI  - Synthesis and HDAC inhibitory activity of isosteric thiazoline-oxazole largazole
      analogs.
AB  - The synthesis of an isosteric analog of the natural product and HDAC inhibitor
      largazole is described. The sulfur atom in the thizaole ring of the natural
      product has been replaced with an oxygen atom, constituting an oxazole ring. The
      biochemical activity and cytotoxicity of this species is described. 

PMID- 24035341
TI  - Anti-inflammatory constituents from the fruits of Vitex rotundifolia.
AB  - Three new diterpenes (7, 15 and 17) and two new neolignans (19 and 20) along with
      nineteen known compounds have been isolated from the fruits of Vitex
      rotundifolia. Their structures were elucidated by a combination of 1D and 2D NMR,
      HRESI-MS, and CD data. All isolates were tested for their inhibitory activities
      on LPS-induced nitric oxide production in RAW264.7 cells. Of these, compounds 3,
      4, 7, 13, 15, 19, and 24 found to inhibit nitric oxide production with the IC50
      values ranging from 11.3 to 24.5MUM. 

PMID- 24035342
TI  - Differentiation of primary chordoma, giant cell tumor and schwannoma of the
      sacrum by CT and MRI.
AB  - OBJECTIVE: To evaluate criteria to differentiate sacral chordoma (SC), sacral
      giant cell tumor (SGCT) and giant sacral schwannoma (GSS) with CT and MRI.
      MATERIALS AND METHODS: CT and MR images of 22 SCs, 19 SGCTs and 8 GSSs were
      reviewed. The clinical and imaging features of each tumor were analyzed. RESULTS:
      The mean ages of SC, SGCT and GSS were 55.1 +/- 10.7, 34.3 +/- 10.7 and 42.4 +/-
      15.7 years old. SCs (77.3%) were predominantly located in the midline of lower
      sacrum, while most SGCTs (73.7%) and GSSs (87.5%) were eccentrically located in
      upper sacrum. There were significant differences in age, location, eccentricity,
      morphology of bone residues, intratumoral bleeding and septations. Multiple small
      cysts were mainly observed in SGCTs (73.7%) with large central cysts in GSSs
      (87.5%). SGCTs expanded mainly inside sacrum while SCs and GSSs often extended
      into pelvic cavity (P = 0.0022). Involvement of sacroiliac joints and muscles
      were also different. Ascending extension within sacral canal was only displayed
      in SCs. The preservation of intervertebral discs showed difference between large
      and small tumors (P = 0.0002), regardless of tumor type (P = 0.095). No
      significant difference was displayed in gender (P = 0.234) or tumor size (P =
      0.0832) among three groups. CONCLUSION: Age, epicenter of the lesion (midline vs.
      eccentric and upper vs. lower sacral vertebra), bone residues, cysts, bleeding,
      septation, expanding pattern, muscles and sacroiliac joint involvement can be
      criteria for diagnosis. Fluid-fluid level is specific for SGCTs and ascending
      extension within the sacral canal for SCs. The preservation of intervertebral
      discs is related to tumor size rather than tumor type.

PMID- 24035343
TI  - The effect of levetiracetam on rat bone mass, structure and metabolism.
AB  - OBJECTIVE: To determine the effect of levetiracetam (LEV) Lon bone mineral
      density (BMD), mineral content (BMC), bone markers, body composition and bone
      mechanical strength in the orchidectomised (ORX) rat model. METHOD: 16
      orchidectomised Wistar rats were divided into control and test groups, 8 rats in
      each group. The control rats received standard laboratory diet (SLD) while rats
      in the test group were fed with SLD enriched with LEV for 12 weeks. BMD was
      measured by dual energy X-ray absorptiometry at the whole body, lumbar spine and
      femur. Bone marker concentrations were examined of osteoprotegerin (OPG) and
      insulin-like growth factor 1 (IGF-1) in serum, and amino-terminal propeptide of
      procollagen type I (PINP), carboxy-terminal cross-linking telopeptide of type I
      collagen (CTX-I), bone alkaline phosphatase (ALPL), and bone morphogenetic
      protein 2 (BMP-2) in bone homogenate. The femurs were used for biomechanical
      testing. RESULTS: Compared to the control group we found lower fat mass, lower
      BMD in the area of the left femur, lower BMC in both femurs, a reduced
      concentration of OPG, and an increased concentration of CTX-I of borderline
      statistical significance (p=0.0661). Biomechanical parameters did not differ
      between groups. CONCLUSIONS: Significant loss of BMD or BMC was seen at the left
      and right femur area in the LEV group. Administration of LEV in the ORX-rat model
      significantly decreased levels of OPG (marker of bone formation) in serum and
      increased levels of CTX-I (marker of bone resorption) in bone homogenate, but
      results in this study did not reveal any change in biomechanical bone strength.
      Administration of LEV in the ORX-rat model may reduce adipose tissue. Further
      studies in animals and humans will be needed to confirm these findings.

PMID- 24035344
TI  - The effects of subanesthetic ketamine infusions on motivation to quit and cue
      induced craving in cocaine-dependent research volunteers.
AB  - BACKGROUND: Cocaine dependence involves problematic neuroadaptations that might
      be responsive to modulation of glutamatergic circuits. This investigation
      examined the effects of subanesthetic ketamine infusions on motivation for
      quitting cocaine and on cue-induced craving in cocaine-dependent participants, 24
      hours postinfusion. METHODS: Eight volunteers with active DSM-IV cocaine
      dependence not seeking treatment or abstinence were entered into this crossover,
      double-blind trial. Three 52-min intravenous infusions were administered:
      ketamine (.41 mg/kg or .71 mg/kg) or lorazepam 2 mg, counterbalanced into three
      orderings in which ketamine .41 mg/kg always preceded the .71 mg/kg dose.
      Infusions were separated by 48 hours, and assessments occurred at baseline and at
      24 hours postinfusion. Outcomes were change between postinfusion and preinfusion
      values for: 1) motivation to quit cocaine scores with the University of Rhode
      Island Change Assessment; and 2) sums of visual analogue scale craving ratings
      administered during cue exposure. RESULTS: Compared with the active control
      lorazepam, a single ketamine infusion (.41 mg/kg) led to a mean 3.9-point gain in
      University of Rhode Island Change Assessment (p = .012), which corresponds to an
      approximately 60% increase over preceding values. There was a reduction of
      comparable magnitude in cue-induced craving (p = .012). A subsequent ketamine
      infusion (.71 mg/kg) led to further reductions in cue-induced craving compared
      with the control. Infusions were well-tolerated. CONCLUSIONS: Subanesthetic
      ketamine demonstrated promising effects on motivation to quit cocaine and on cue
      induced craving, 24 hours postinfusion. Research is needed to expand on these
      preliminary results and to evaluate the efficacy of this intervention in clinical
      settings.

PMID- 24035346
TI  - Subcellular location of astrocytic calcium stores favors extrasynaptic neuron
      astrocyte communication.
AB  - Neuron-astrocyte interactions are important for brain computations and synaptic
      plasticity. Perisynaptic astrocytic processes (PAPs) contain a high density of
      transporters that are responsible for neurotransmitter clearance. Metabotropic
      glutamate receptors are thought to trigger Ca(2+) release from Ca(2+) stores in
      PAPs in response to synaptic activity. Our ultrastructural study revealed that
      PAPs are actually devoid of Ca(2+) stores and have a high surface-to-volume ratio
      favorable for uptake. Astrocytic processes containing Ca(2+) stores were located
      further away from the synapses and could therefore respond to changes in ambient
      glutamate. Thus, the anatomic data do not support communication involving Ca(2+)
      stores in tripartite synapses, but rather point to extrasynaptic communication. 

PMID- 24035345
TI  - Imaging glutamate homeostasis in cocaine addiction with the metabotropic
      glutamate receptor 5 positron emission tomography radiotracer [(11)C]ABP688 and
      magnetic resonance spectroscopy.
AB  - BACKGROUND: Preclinical studies demonstrate that glutamate homeostasis in the
      striatum is disrupted following cocaine exposure, including a decrease in
      metabotropic glutamate receptor type 5 (mGluR5) expression and reduced glutamate
      turnover. The goal of this study was to use imaging of the human brain to
      investigate alterations in the glutamate signaling in cocaine addiction. METHODS:
      Positron emission tomography imaging with the radiotracer [(11)C]ABP688 was used
      to measure mGluR5 binding and magnetic resonance spectroscopy was used to measure
      glutamate-glutamine levels in the striatum of cocaine-addicted participants (n =
      15) compared with healthy control subjects (n = 15). Following the scans, the
      cocaine-addicted volunteers performed cocaine self-administration sessions to
      investigate the correlation between cocaine-seeking behavior and mGluR5 receptor
      binding. RESULTS: The results of the study showed that cocaine addiction was
      associated with a 20% to 22% reduction in [(11)C]ABP688 binding in the striatum.
      A secondary analysis of cortical and subcortical regions other than the striatum
      showed a similar reduction in [(11)C]ABP688 binding, suggesting that the decrease
      was widespread. No between-group differences were seen in the magnetic resonance
      spectroscopy measures of glutamate-glutamine in the left striatum. In addition,
      no correlation was seen between [(11)C]ABP688 binding in the striatum and the
      choice to self-administer cocaine. CONCLUSIONS: Overall, these results show that
      long-term cocaine use is associated with a decrease in mGluR5 availability
      compared with matched healthy control subjects and suggests that this receptor
      may serve as a viable target for treatment development for this disorder.

PMID- 24035347
TI  - On the hazard of quiet vehicles to pedestrians and drivers.
AB  - The need to produce more efficient and less polluting vehicles has encouraged
      mass production of alternative energy vehicles, such as hybrid and electric cars.
      Many of these vehicles are capable of very quiet operation. While reducing noise
      pollution is desirable, quieter vehicles could negatively affect pedestrian
      safety because of reduced sound cues compared to louder internal combustion
      engines. Three studies were performed to investigate people's concern about this
      issue. In Study 1, a questionnaire completed by 378 people showed substantial
      positive interest in quiet hybrid and electric cars. However, they also indicated
      concern about the reduced auditory cues of quiet vehicles. In Study 2, 316
      participants rated 14 sounds that could be potentially added to quiet alternative
      energy vehicles. The data showed that participants did not want annoying sounds,
      but preferred adding "engine" and "hum" sounds relative to other types of sounds.
      In Study 3, 24 persons heard and rated 18 actual sounds within 6 categories that
      were added to a video of a hybrid vehicle driving by. The sounds most preferred
      were "engine" followed by "white noise" and "hum". Implications for adding sounds
      to facilitate pedestrians' detection of moving vehicles and for aiding drivers'
      awareness of speed are discussed.

PMID- 24035348
TI  - Metabolic syndrome and functional ability in older age: the InCHIANTI study.
AB  - BACKGROUND & AIMS: Metabolic syndrome (MetS) is associated with incident
      disability in middle-aged subjects. We evaluated the association of MetS with
      functional ability in an older population. METHODS: We enrolled 1155 participants
      aged 65+, derived from the InCHIANTI study, and followed for 3 years. MetS was
      diagnosed according to the National Cholesterol Education Program's ATP-III
      criteria. Functional ability was estimated using the Katz's activities of daily
      living (ADLs), and the Lawton and Brody for the instrumental activities of daily
      living (IADLs) scales. The association between disability and MetS at baseline
      and after follow-up was assessed by logistic regression. RESULTS: At baseline,
      MetS was associated with reduced probability of ADLs disability among
      participants aged 74+ (OR = .33, 95% CI = .14-.77; p = .010), but not in younger
      (5.08, 95% CI = .88-29.24; p = .069). Also, MetS was associated with reduced
      probability of incident ADLs disability (OR = .61, 95% CI .41-.91; p = .016), but
      neither with prevalent, nor incident IADLs disability. CONCLUSIONS: In older
      persons, MetS is associated with reduced probability of prevalent and incident
      ADLs disability. Whether older persons with MetS should receive treatment and
      whether the current diagnostic criteria for MetS apply to older individuals need
      further investigation.

PMID- 24035350
TI  - Primary motor cortex function in complex regional pain syndrome: a systematic
      review and meta-analysis.
AB  - Dysfunction in the central nervous system is thought to underlie the movement
      disorders that commonly occur in complex regional pain syndrome (CRPS), with much
      of the literature focusing on reorganization of the primary motor cortex (M1).
      Presumed changes in the M1 representation of the CRPS-affected body part have
      contributed to new CRPS treatments, which are increasingly being integrated in
      the clinic. We systematically investigated the evidence for altered M1 function
      in CRPS. We adhered to rigorous systematic review procedure in our search
      strategy, risk-of-bias appraisal, and data extraction. Eighteen studies
      comprising 14 unique data sets were included. The included studies used several
      neuroimaging techniques, whose outcomes we grouped into M1 cortical excitability,
      spatial representation, reactivity, and glucose metabolism, and conducted meta
      analyses where possible. Risk of bias across studies was high, mainly due to
      missing data and unblinded assessment of outcomes. No definitive conclusions can
      be drawn regarding M1 spatial representation, reactivity, or glucose metabolism
      in CRPS. There is limited evidence for bilateral M1 disinhibition in CRPS of the
      upper limb. PERSPECTIVE: Despite widely held assumptions of primary motor cortex
      dysfunction in complex regional pain syndrome, there is only evidence to support
      bilateral disinhibition, and there is high risk of bias across the literature.

PMID- 24035351
TI  - A trial of a brief group-based form of acceptance and commitment therapy (ACT)
      for chronic pain in general practice: pilot outcome and process results.
AB  - Acceptance and commitment therapy (ACT) is a developing approach for chronic
      pain. The current study was designed to pilot test a brief, widely inclusive,
      local access format of ACT in a UK primary care setting. Seventy-three
      participants (68.5% women) were randomized to either ACT or treatment as usual
      (TAU). Many of the participants were aged 65 years or older (27.6%), were
      diagnosed with fibromyalgia (30.2%) and depression (40.3%), and had longstanding
      pain (median = 10 years). Standard clinical outcome measures included disability,
      depression, physical functioning, emotional functioning, and rated improvement.
      Process measures included pain-related and general psychological acceptance. The
      recruitment target was met within 6 months, and 72.9% of those allocated to ACT
      completed treatment. Immediately post treatment, relative to TAU, participants in
      ACT demonstrated lower depression and higher ratings of overall improvement. At a
      3-month follow-up, again relative to TAU, those in ACT demonstrated lower
      disability, less depression, and significantly higher pain acceptance; d = .58,
      .59, and .64, respectively. Analyses based on intention-to-treat and on treatment
      "completers," perhaps predictably, revealed more sobering and more encouraging
      results, respectively. A larger trial of ACT delivered in primary care, in the
      format employed here, appears feasible with some recommended adjustments in the
      methods used here (Trial registration: ISRCTN49827391). PERSPECTIVE: This article
      presents a pilot randomized controlled trial of ACT for chronic pain in a primary
      care setting in the United Kingdom. Both positive clinical outcomes and ways to
      improve future trials are reported.

PMID- 24035352
TI  - Disruption of fast axonal transport in the rat induces behavioral changes
      consistent with neuropathic pain.
AB  - Studies of peripheral nerve inflammation (neuritis) suggest that some symptoms of
      neuropathic pain can be generated from inflamed but otherwise uninjured axons. We
      have previously inferred a role for inflammation-induced axonal transport
      disruption in the underlying mechanisms. In the present study, we have
      investigated the development of sensory hypersensitivities following vinblastine
      induced axonal transport disruption. Similar to neuritis, locally applied .1 mM
      vinblastine caused the rapid development of mechanical hypersensitivity within
      the first week postsurgery. The same animals did not develop heat
      hypersensitivity. Because aberrant firing from primary sensory neurons is
      considered necessary to drive spinal mechanisms that lead to hypersensitivities,
      the levels of ongoing activity and axonal mechanical sensitivity were examined.
      Recordings from A- and C-fiber neurons did not reveal differences in the levels
      of ongoing activity between vinblastine-treated (<5.8%) and saline-treated
      control animals (<4.6%). However, 28% of C-fiber axons were mechanically
      sensitive at the vinblastine treatment site. Using kinesin immunohistochemistry,
      we confirmed a reduction of anterograde axonal transport in vinblastine-treated
      and neuritis animals. In summary, this study has revealed an alternative pain
      model, which may be relevant to conditions that are not accompanied by frank
      nerve injury. PERSPECTIVE: In this study, we expand our previous reports and
      demonstrate that focal reduced axonal transport causes distal mechanical
      hypersensitivity considered consistent with neuropathic pain but in the absence
      of nerve injury. These findings may inform pain conditions that have a neural
      inflammatory component.

PMID- 24035349
TI  - An overview of animal models of pain: disease models and outcome measures.
AB  - Pain is ultimately a perceptual phenomenon. It is built from information gathered
      by specialized pain receptors in tissue, modified by spinal and supraspinal
      mechanisms, and integrated into a discrete sensory experience with an emotional
      valence in the brain. Because of this, studying intact animals allows the
      multidimensional nature of pain to be examined. A number of animal models have
      been developed, reflecting observations that pain phenotypes are mediated by
      distinct mechanisms. Animal models of pain are designed to mimic distinct
      clinical diseases to better evaluate underlying mechanisms and potential
      treatments. Outcome measures are designed to measure multiple parts of the pain
      experience, including reflexive hyperalgesia measures, sensory and affective
      dimensions of pain, and impact of pain on function and quality of life. In this
      review, we discuss the common methods used for inducing each of the pain
      phenotypes related to clinical pain syndromes as well as the main behavioral
      tests for assessing pain in each model. PERSPECTIVE: Understanding animal models
      and outcome measures in animals will assist in translating data from basic
      science to the clinic.

PMID- 24035353
TI  - Mapping cellular hierarchy by single-cell analysis of the cell surface
      repertoire.
AB  - Stem cell differentiation pathways are most often studied at the population
      level, whereas critical decisions are executed at the level of single cells. We
      have established a highly multiplexed, quantitative PCR assay to profile in an
      unbiased manner a panel of all commonly used cell surface markers (280 genes)
      from individual cells. With this method, we analyzed over 1,500 single cells
      throughout the mouse hematopoietic system and illustrate its utility for
      revealing important biological insights. The comprehensive single cell data set
      permits mapping of the mouse hematopoietic stem cell differentiation hierarchy by
      computational lineage progression analysis. Further profiling of 180
      intracellular regulators enabled construction of a genetic network to assign the
      earliest differentiation event during hematopoietic lineage specification.
      Analysis of acute myeloid leukemia elicited by MLL-AF9 uncovered a distinct
      cellular hierarchy containing two independent self-renewing lineages with
      different clonal activities. The strategy has broad applicability in other
      cellular systems. 

PMID- 24035355
TI  - Continuous clonal labeling reveals small numbers of functional stem cells in
      intestinal crypts and adenomas.
AB  - Lineage-tracing approaches, widely used to characterize stem cell populations,
      rely on the specificity and stability of individual markers for accurate results.
      We present a method in which genetic labeling in the intestinal epithelium is
      acquired as a mutation-induced clonal mark during DNA replication. By determining
      the rate of mutation in vivo and combining this data with the known neutral-drift
      dynamics that describe intestinal stem cell replacement, we quantify the number
      of functional stem cells in crypts and adenomas. Contrary to previous reports, we
      find that significantly lower numbers of "working" stem cells are present in the
      intestinal epithelium (five to seven per crypt) and in adenomas (nine per gland),
      and that those stem cells are also replaced at a significantly lower rate. These
      findings suggest that the bulk of tumor stem cell divisions serve only to replace
      stem cell loss, with rare clonal victors driving gland repopulation and tumor
      growth.

PMID- 24035354
TI  - Long-range chromatin contacts in embryonic stem cells reveal a role for
      pluripotency factors and polycomb proteins in genome organization.
AB  - The relationship between 3D organization of the genome and gene-regulatory
      networks is poorly understood. Here, we examined long-range chromatin
      interactions genome-wide in mouse embryonic stem cells (ESCs), iPSCs, and
      fibroblasts and uncovered a pluripotency-specific genome organization that is
      gradually reestablished during reprogramming. Our data confirm that long-range
      chromatin interactions are primarily associated with the spatial segregation of
      open and closed chromatin, defining overall chromosome conformation.
      Additionally, we identified two further levels of genome organization in ESCs
      characterized by colocalization of regions with high pluripotency factor
      occupancy and strong enrichment for Polycomb proteins/H3K27me3, respectively.
      Underlining the independence of these networks and their functional relevance for
      genome organization, loss of the Polycomb protein Eed diminishes interactions
      between Polycomb-regulated regions without altering overarching chromosome
      conformation. Together, our data highlight a pluripotency-specific genome
      organization in which pluripotency factors such as Nanog and H3K27me3 occupy
      distinct nuclear spaces and reveal a role for cell-type-specific gene-regulatory
      networks in genome organization.

PMID- 24035356
TI  - Hollow graphitic nanocapsules as efficient electrode materials for sensitive
      hydrogen peroxide detection.
AB  - Carbon nanomaterials are typically used in electrochemical biosensing
      applications for their unique properties. We report a hollow graphitic
      nanocapsule (HGN) utilized as an efficient electrode material for sensitive
      hydrogen peroxide detection. Methylene blue (MB) molecules could be efficiently
      adsorbed on the HGN surfaces, and this adsorption capability remained very stable
      under different pH regimes. HGNs were used as three-dimensional matrices for
      coimmobilization of MB electron mediators and horseradish peroxidase (HRP) to
      build an HGN-HRP-MB reagentless amperometric sensing platform to detect hydrogen
      peroxide. This simple HGN-HRP-MB complex demonstrated very sensitive and
      selective hydrogen peroxide detection capability, as well as high reproducibility
      and stability. The HGNs could also be utilized as matrices for immobilization of
      other enzymes, proteins or small molecules and for different biomedical
      applications.

PMID- 24035357
TI  - Prevalence and risk factors for diabetes-related foot complications in
      Translating Research Into Action for Diabetes (TRIAD).
AB  - AIMS: The objective was to describe the prevalence of diabetes-related foot
      complications in a managed care population and to identify the demographic and
      biological risk factors. METHODS: We assessed the period prevalence of foot
      complications on 6992 patients using ICD-9 diagnosis codes from health plan
      administrative data. Demographic and biological variables were ascertained from
      surveys and medical record reviews. We defined four mutually exclusive groups:
      any Charcot foot, DFU with debridement, amputation+/-DFU and debridement, and no
      foot conditions. RESULTS: Overall, 55 (0.8%) patients had Charcot foot, 205
      (2.9%) had DFU with debridement, and 101 (1.4%) had a lower-extremity amputation.
      There were 6631 patients with no prevalent foot conditions. Racial/ethnic
      minorities were less likely to have Charcot foot (OR=0.21; 95% CI: 0.10, 0.46) or
      DFU (OR=0.61; 95% CI: 0.44, 0.84) compared to non-Hispanic Whites, but there were
      no racial/ethnic differences in amputation. Histories of micro- or macrovascular
      disease were associated with a two- to four-fold increase in the odds of foot
      complications. CONCLUSION: In managed care patients with uniform access to health
      care, we found a relatively high prevalence of foot complications, but
      attenuation of the racial/ethnic differences of rates reported in the literature.

PMID- 24035358
TI  - The expression and role of miR-301a in human umbilical cord-derived mesenchymal
      stromal cells.
AB  - BACKGROUND AIMS: Toll-like receptors (TLRs) are expressed in human umbilical cord
      derived mesenchymal stromal cells (UC-MSCs), and activation of TLRs plays an
      important role in proliferation, differentiation and immunoregulatory activity of
      UC-MSCs. We investigated whether TLRs regulated the expression of microRNAs
      (miRNAs) in UC-MSCs and the role of miRNAs. METHODS AND RESULTS: With miRNA
      microarray analysis, we demonstrated that the expression of many miRNAs varied
      when UC-MSCs were stimulated with the ligand of toll-like receptor 4 (TLR4),
      lipopolysaccharide (LPS). The expression of some miRNAs was verified by
      polymerase chain reaction. It was found that microRNA-301a (miR-301a) was up
      regulated by the ligands of TLR3 and TLR4, LPS and polyinosinic
      acid:polycytidylic acid poly(I:C). However, the inhibitors of nuclear factor
      kappaB NF-kappaB and interferon regulatory factor 3 IRF3 signal attenuated the
      effect of LPS and poly(I:C) on miR-301a expression. Over-expression or lower
      expression of miR-301a affected the cytokine secretion of UC-MSCs. CONCLUSIONS:
      The expression of miR-301a in UC-MSCs was regulated by TLRs, and miR-301a
      affected the cytokine secretion of UC-MSCs.

PMID- 24035359
TI  - [Acromegaly and pregnancy: report of six new cases].
AB  - INTRODUCTION: Pregnancies in acromegalic women are rare. Data from the literature
      indicate absence of congenital malformation in newborns, an increase of pituitary
      adenoma volume rarely clinically symptomatic, an increased risk of gestational
      diabetes and gravid hypertension in women with non-controlled GH/IGF-1
      hypersecretion before gestation. The changes of somatotroph function are rarely
      described. AIM OF THE STUDY: Report of six new pregnancies in five women with
      acromegaly. PATIENTS AND METHODS: Before pregnancy three women had incomplete
      surgical resection of GH-secreting pituitary adenoma, all were treated with
      somatostatin analogues, and the medical treatment was withdrawal at the diagnosis
      of gestation. We studied clinical (blood pressure, headaches, visual field),
      biological (blood glucose concentration) signs, GH and IGF-1 levels were measured
      during each trimester of pregnancy as well as in post-partum and were compared
      with pregestational values, MRI of the pituitary performed during the second
      trimester and in the post-partum were compared with MRI examen before pregnancy.
      RESULTS: All those pregnancies were normal without gestational diabetes, gravid
      hypertension and pituitary tumor syndrome. Clinical signs of acromegaly improved
      in 50 % of the patients, and IGF-1 decreased (22 %) in comparison of
      pregestational value without significant change in GH levels. No newborn had
      congenital malformation. CONCLUSION: Pregnancies in those women with acromegaly
      are uneventful without obstetrical or foetal complication, but a maternal follow
      up is necessary in order to diagnose gravid hypertension and gestational
      diabetes. On the other hand, a clinical monitoring of pituitary tumor syndrome is
      necessary in women with non-operated GH-secreting macroadenoma before pregnancy.
      During the first trimester of gestation, an improvement of acromegalic signs can
      be due to a decrease of IGF-1 levels related to hepatic GH-resistance state
      secondary to physiological secretion of estrogens during gestation.

PMID- 24035361
TI  - Comparative study of both versions of an immunoassay commercialized for
      therapeutic drug monitoring of adalimumab in rheumatoid arthritis.
AB  - OBJECTIVE: To describe the results of the comparative study between both versions
      of an immunoassay commercialized for therapeutic drug monitoring of adalimumab
      (ADA) in rheumatoid arthritis (AR). MATERIAL AND METHODS: 140 samples of patients
      with RA treated with ADA 40mg every 14 days were analyzed by both versions of the
      test (V1 or previous and V2 or updated). RESULTS: A good correlation was obtained
      by both versions. In general V2 provides higher results of ADA's concentration
      than V1 and presents greater precision in the range of concentrations for
      clinical decisions, adjusting for the real concentration of the drug in blood. In
      addition, V2 allows for complete automation, which simplifies the analysis and
      reduces significantly the variability. CONCLUSION: ADA's monitoring with the
      updated version demonstrated to have technical significant advantages,
      constituting a more practical tool for therapeutic decisions in patients with RA.

PMID- 24035362
TI  - Evaluation of lip sensory disturbance using somatosensory evoked magnetic fields.
AB  - OBJECTIVE: To evaluate lip sensory dysfunction in patients with inferior alveolar
      nerve injury by lip-stimulated somatosensory evoked fields (SEFs). METHODS: SEFs
      were recorded following electrical lip stimulation in 6 patients with unilateral
      lip sensory disturbance and 10 healthy volunteers. Lip stimulation was applied
      non-invasively to each side of the lip with the same intensity using pin
      electrodes. RESULTS: All healthy volunteers showed the earliest response clearly
      and consistently at around 25ms (P25m) and at least one of the following
      components, P45m, P60m, or P80m, over the contralateral hemisphere. The ranges of
      the peak latencies were 23-33, 42-50, 56-67, and 72-98ms for right-side
      stimulation and 23-34, 46-49, 52-68, and 71-90ms for left-side stimulation.
      Affected-side stimulation did not evoke P25m component in any patients, but
      invoked traceable responses in 5 patients whose latencies were 57, 89, 65, 53,
      and 54ms. Unaffected-side stimulation induced P25m in 2 patients at 27 and 25ms,
      but not in the other 4 patients. CONCLUSION: The P25m component of lip SEFs can
      be an effective parameter to indicate lip sensory abnormality. SIGNIFICANCE: Lip
      sensory dysfunction can be objectively evaluated using magnetoencephalography.

PMID- 24035363
TI  - Monocyte-derived dendritic cells perform hemophagocytosis to fine-tune excessive
      immune responses.
AB  - Because immune responses simultaneously defend and injure the host, the immune
      system must be finely regulated to ensure the host's survival. Here, we have
      shown that when injected with high Toll-like receptor ligand doses or infected
      with lymphocytic choriomeningitis virus (LCMV) clone 13, which has a high viral
      turnover, inflammatory monocyte-derived dendritic cells (Mo-DCs) engulfed
      apoptotic erythroid cells. In this process, called hemophagocytosis,
      phosphatidylserine (PS) served as an "eat-me" signal. Type I interferons were
      necessary for both PS exposure on erythroid cells and the expression of PS
      receptors in the Mo-DCs. Importantly, hemophagocytosis was required for
      interleukin-10 (IL-10) production from Mo-DCs. Blocking hemophagocytosis or Mo-DC
      derived IL-10 significantly increased cytotoxic T cell lymphocyte activity,
      tissue damage, and mortality in virus-infected hosts, suggesting that
      hemophagocytosis moderates immune responses to ensure the host's survival in
      vivo. This sheds light on the physiological relevance of hemophagocytosis in
      severe inflammatory and infectious diseases. 

PMID- 24035364
TI  - Autophagy regulates phagocytosis by modulating the expression of scavenger
      receptors.
AB  - Autophagy and phagocytosis are conserved cellular functions involved in innate
      immunity. However, the nature of their interactions remains unclear. We evaluated
      the role of autophagy in regulating phagocytosis in macrophages from myeloid
      specific autophagy-related gene 7-deficient (Atg7-/-) mice. Atg7-/- macrophages
      exhibited higher bacterial uptake when infected with Mycobacterium tuberculosis
      (Mtb) or with M. tuberculosis var. bovis BCG (BCG). In addition, BCG-infected
      Atg7-/- mice showed increased bacterial loads and exacerbated lung inflammatory
      responses. Atg7-/- macrophages had increased expression of two class A scavenger
      receptors: macrophage receptor with collagenous structure (MARCO) and macrophage
      scavenger receptor 1 (MSR1). The increase in scavenger receptors was caused by
      increased activity of the nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)
      transcription factor resulting from accumulated sequestosome 1 (SQSTM1 or p62) in
      Atg7-/- macrophages. These insights increase our understanding of the host
      pathogen relationship and suggest that therapeutic strategies should be designed
      to include modulation of both phagocytosis and autophagy.

PMID- 24035366
TI  - Obesity prevalence among youth investigated for maltreatment in the United
      States.
AB  - The objective of this study is to determine the prevalence and correlates of
      obesity among youth investigated for maltreatment in the United States.
      Participants were drawn from the National Survey of Child and Adolescent Well
      Being II, a national probability study of 5,873 children aged birth to 17 years
      under investigation for maltreatment in 2008. From child weight reported by
      caregivers, we estimated obesity (weight-for-age >=95th percentile) prevalence
      among children aged 2 through 17 (n=2,948). Sex-specific logistic regression
      models by developmental age were used to identify obesity risk factors, including
      child age, race/ethnicity, and maltreatment type. Obesity prevalence was 25.4%
      and was higher among boys than girls (30.0% vs. 20.8%). African American
      adolescent boys had a lower risk for obesity than white boys (OR=0.28, 95% CI
      [0.08, 0.94]). Compared with girls aged 2-5 with a neglect allegation, girls with
      a sexual abuse allegation were at greater risk for obesity (OR=3.54, 95% CI
      [1.01, 12.41]). Compared with adolescent boys with a neglect allegation, boys
      with a physical abuse allegation had a lower risk for obesity (OR=0.24, 95% CI
      [0.06, 0.99]). Adolescent girls with a prior family history of investigation were
      at greater risk for obesity than those without a history of investigation
      (OR=3.97, 95% CI [1.58, 10.02]). Youth investigated for maltreatment have high
      obesity rates compared with national peers. Opportunities to modify and evaluate
      related child welfare policies and health care practices should be pursued. 

PMID- 24035365
TI  - Human circulating PD-1+CXCR3-CXCR5+ memory Tfh cells are highly functional and
      correlate with broadly neutralizing HIV antibody responses.
AB  - The vast majority of currently licensed human vaccines work on the basis of long
      term protective antibody responses. It is now conceivable that an antibody
      dependent HIV vaccine might be possible, given the discovery of HIV broadly
      neutralizing antibodies (bnAbs) in some HIV-infected individuals. However, these
      antibodies are difficult to develop and have characteristics indicative of a high
      degree of affinity maturation in germinal centers (GCs). CD4+ T follicular helper
      (Tfh) cells are specialized for B cell help and necessary for GCs. Therefore, the
      development of HIV bnAbs might depend on Tfh cells. Here, we identified in normal
      individuals a subpopulation of circulating memory PD-1+CXCR5+CD4+ T cells that
      are resting memory cells most related to bona fide GC Tfh cells by gene
      expression profile, cytokine profile, and functional properties. Importantly, the
      frequency of these cells correlated with the development of bnAbs against HIV in
      a large cohort of HIV+ individuals.

PMID- 24035368
TI  - A coming of age: advanced imaging technologies for characterising the developing
      mouse.
AB  - The immense challenge of annotating the entire mouse genome has stimulated the
      development of cutting-edge imaging technologies in a drive for novel
      information. These techniques promise to improve understanding of the genes
      involved in embryo development, at least one third of which have been shown to be
      essential. Aligning advanced imaging technologies with biological needs will be
      fundamental to maximising the number of phenotypes discovered in the coming
      years. International efforts are underway to meet this challenge through an
      integrated and sophisticated approach to embryo phenotyping. We review rapid
      advances made in the imaging field over the past decade and provide a
      comprehensive examination of the relative merits of current and emerging
      techniques. The aim of this review is to provide a guide to state-of-the-art
      embryo imaging that will enable informed decisions as to which technology to use
      and fuel conversations between expert imaging laboratories, researchers, and core
      mouse production facilities. 

PMID- 24035367
TI  - Amputee locomotion: lower extremity loading using running-specific prostheses.
AB  - Carbon fiber running-specific prostheses (RSPs) have allowed individuals with
      lower extremity amputation (ILEA) to actively participate in sporting activities
      including competitive sports. In spite of this positive trait, the RSPs have not
      been thoroughly evaluated regarding potential injury risks due to abnormal
      loading during running. Vertical impact peak (VIP) and average loading rate
      (VALR) of the vertical ground reaction force (vGRF) have been associated with
      running injuries in able-bodied runners but not for ILEA. The purpose of this
      study was to investigate vGRF loading in ILEA runners using RSPs across a range
      of running speeds. Eight ILEA with unilateral transtibial amputations and eight
      control subjects performed overground running at three speeds (2.5, 3.0, and
      3.5m/s). From vGRF, we determined VIP and VALR, which was defined as the change
      in force divided by the time of the interval between 20 and 80% of the VIP. We
      observed that VIP and VALR increased in both ILEA and control limbs with an
      increase in running speed. Further, the VIP and VALR in ILEA intact limbs were
      significantly greater than ILEA prosthetic limbs and control subject limbs for
      this range of running speeds. These results suggest that (1) loading variables
      increase with running speed not only in able-bodied runners, but also in ILEA
      using RSPs, and (2) the intact limb in ILEA may be exposed to a greater risk of
      running related injury than the prosthetic limb or able-bodied limbs.

PMID- 24035369
TI  - Surgical outcomes after application of a liquid adhesive ocular bandage to clear
      corneal incisions during cataract surgery.
AB  - PURPOSE: To compare the anatomic and refractive outcomes in eyes having
      phacoemulsification with 1 of 3 clear corneal incision (CCI) closure methods.
      SETTING: Ambulatory surgical center, Makati, Philippines. DESIGN: Prospective
      randomized clinical trial. METHODS: Patients having phacoemulsification cataract
      surgery had wound closure using no additional treatment (control), a single 10-0
      nylon suture, or a liquid adhesive ocular bandage (Ocuseal). The main outcome
      measures were wound-edge closure rates, surgically induced astigmatism (SIA),
      foreign-body sensation, and intraocular pressure (IOP) 1, 3, 5, 7, and 14 days
      postoperatively. RESULTS: The study evaluated 90 eyes. There was a significant
      improvement in wound-edge closure rates in the suture group and the ocular
      bandage group compared with the control group (P<.001). A significant increase in
      SIA occurred in the sutured group but not in the control or ocular bandage groups
      (P<.001). The ocular bandage group had significantly less foreign-body sensation
      than the control and suture groups (P<.001). There were no significant
      differences in IOP between the groups (P=.515). CONCLUSIONS: The liquid adhesive
      ocular bandage resulted in improved wound-edge closure, reduced SIA, and
      diminished foreign-body sensation. Suturing was associated with improved wound
      edge closure but increased SIA and foreign-body sensation. Unsutured incisions
      led to delayed wound-edge closure and increased foreign-body sensation.

PMID- 24035370
TI  - Minimally invasive aortic valve replacement using right minithoracotomy is
      associated with better outcomes than ministernotomy.
AB  - OBJECTIVE: To compare the outcomes of right minithoracotomy (RT) versus
      ministernotomy (MS) in patients undergoing minimally invasive aortic valve
      replacement (AVR). METHODS: From January 2005 to December 2011, 406 patients
      underwent minimally invasive AVR, of whom 251 patients were in the RT group and
      155 were in the MS group. RESULTS: The overall in-hospital mortality was 1.2%
      with no difference between the 2 groups (1.2% in RT vs 1.3% in MS). Patients
      undergoing minimally invasive AVR using RT had a lower incidence of postoperative
      atrial fibrillation (19.5% vs 34.2%, P = .01), shorter ventilation time (median,
      7 vs 8 hours; interquartile range, 5-9 vs 6-12 hours, P = .003), intensive care
      unit stay (median 1 vs 1 day; interquartile range, 1-1 vs 1-2 days; P = .001),
      and hospital stay (median, 5 vs 6 days; interquartile range, 5-6 vs 5-8 days; P =
      .0001). No difference was found in terms of cardiopulmonary time, crossclamping
      time, postoperative stroke, re-exploration for bleeding, or blood transfusion.
      CONCLUSIONS: Minimally invasive AVR using RT was associated with lower
      postoperative morbidities and a shorter hospital stay than MS.

PMID- 24035371
TI  - Proximal thoracic aortic aneurysm mimicking a mediastinal neoplasm.

PMID- 24035372
TI  - Mitral valve annular downsizing forces: implications for annuloplasty device
      development.
AB  - OBJECTIVE: Mitral valve repair with annulus downsizing is a popular surgical
      procedure for functional mitral regurgitation. We investigated the effects of
      externally applied downsizing on the observed in-plane forces and valvular
      dimensions. METHODS: Five animals were included in an acute porcine study. Three
      traction sutures were anchored at the right fibrous trigone (T) and suspended
      across the annulus for externalization at the P1, P2, and P3 annular segments.
      The annulus was downsized with the sutures in controlled increments while
      measuring the tension force in the sutures. Downsizing percentages ranged from a
      2% to 32% reduction of the T-P distances. Sonomicrometry was used to measure the
      resulting valvular dimensions. RESULTS: No difference in force was found between
      the P1, P2, and P3 segments across all levels of downsizing. The peak forces at
      32% downsizing were 1.2 +/- 0.9 N, 1.5 +/- 1.0 N, and 0.8 +/- 0.2 N for the T-P1,
      T-P2, and T-P3 segments, respectively. The maximum total suture forces in the
      mitral plane during downsizing increased from 0.12 +/- 0.03 N to 3.5 +/- 1.3 N (P
      < .005). Sonomicrometry showed a decrease in the systolic thickening of the
      posterior myocardial wall at the annular level with annular downsizing (0%-32%)
      from 5 +/- 3 mm to 1 +/- 1 mm (P < .05). CONCLUSIONS: Segmental mitral valve
      annulus downsizing increased in-plane traction suture forces and has a
      significant influence on the in-plane biomechanics. These results have
      implications for device design in terms of mechanical strength requirements and
      can be used to supplement boundary conditions for computational left heart
      models.

PMID- 24035373
TI  - Early experience with off-the-shelf endografts using a zone 0 proximal landing
      site to treat the ascending aorta and arch.
AB  - OBJECTIVE: Acute type A aortic syndromes and its chronic complications are fatal
      diseases traditionally treated by open surgery, with high mortality rates. An
      endovascular approach to the ascending aorta could reduce the morbidity and
      mortality associated with open surgery. Our aim was to report our initial
      experience in treating ascending aortic pathology using commercially available
      descending thoracic endografts. METHODS: From 2007 to 2012, 69 patients presented
      to our center in Belo Horizonte, Brazil, with acute type A aortic syndrome or its
      chronic complications. Of the 69 patients, 8 high-risk patients had suitable
      anatomy, and 7 agreed to participate in the present study. RESULTS: Of the 7
      patients, 4 had penetrating ulcers, 2 had acute dissections, and 1 had chronic
      dissection with an aneurysm. The technical success rate was 87%, with 1
      intraoperative death from acute aortic valve insufficiency. The proximal landing
      zone was, on average, 21 mm above the aortic valve in all patients. Three
      patients required intraoperative cervical debranching due to a lesion in the
      distal third of the ascending aorta, compromising the supra-aortic branches. The
      distal landing zone was at zone 0 in 4 patients, zone 2 in 1 patient, and in zone
      4 in 2 patients. The mean follow-up was 26.3 months. Two repeat dissections
      developed an average of 2 months after treatment. Both presented with acute
      dissection that was treated with additional open surgery and both patients
      survived. Thereafter, no patient had presented again with an acute aortic
      syndrome or other referable symptoms. CONCLUSIONS: Endovascular treatment of the
      ascending aorta is feasible. We had 4 good mid-term results in 7 patients who had
      presented with penetrating ulcers or aneurysm formation. Acute dissections seem
      to be more unstable, and additional research is mandatory.

PMID- 24035374
TI  - Moderate mitral regurgitation in aortic root replacement surgery: comparing
      mitral repair with no mitral repair.
AB  - OBJECTIVES: Patients often present for aortic root replacement surgery with
      concomitant mitral valve pathology. Moderate mitral regurgitation is the point of
      clinical equipoise where the benefits of intervention compared with observation
      are currently unknown. This study compares outcomes in patients undergoing aortic
      root replacement surgery who did or did not receive a mitral valve repair for
      their preoperative moderate mitral regurgitation. METHODS: A total of 1316
      patients who underwent aortic root replacement surgery between 2000 and 2011 were
      evaluated, with 104 patients meeting the inclusion criteria by presenting with
      moderate preoperative mitral regurgitation. A total of 73 patients (70%) received
      no mitral intervention, and 31 patients (30%) received a mitral repair. Patients
      underwent preoperative, postoperative, and greater than 6-month follow-up
      echocardiograms. Average clinical follow-up was 6.5 years. RESULTS: The mitral
      repair group had increased preoperative New York Heart Association III/IV and
      heart failure, longer crossclamp times, and more postoperative renal failure (P =
      .0003, P = .04, P < .0001, and P = .03, respectively). The improvement in mitral
      regurgitation was greater for the mitral repair group (-2.1 +/- 0.3 vs -1.1 +/-
      0.8, P < .0001), and mitral regurgitation remained significantly lower on follow
      up at 6 months or more (0.6 +/- 0.4 0.9 +/- 0.2, P = .002). A significantly
      greater percentage of patients undergoing mitral repair compared with patients
      with no repair had improvement of at least 1 grade in mitral regurgitation
      postoperatively (100% vs 70%, P = .001) and on follow-up at 6 months or more (90%
      vs 61%, P = .006). There was no difference in long-term survival, freedom from 2+
      or greater mitral regurgitation, or mitral reinterventions. CONCLUSIONS: Mitral
      repair along with aortic root replacement has acceptable operative risk. Aortic
      root replacement surgery alone improved mitral regurgitation, but the addition of
      mitral repair further reduced mitral regurgitation, suggesting that repairing
      moderate mitral regurgitation should generally be considered along with aortic
      root replacement.

PMID- 24035375
TI  - Four-year follow-up after thoracic endovascular aortic repair for symptomatic
      thoracoabdominal aneurysm through the off-label use of a bifurcated abdominal
      endograft.

PMID- 24035376
TI  - Discussion.

PMID- 24035377
TI  - Early patency rate and fate of reattached intercostal arteries after repair of
      thoracoabdominal aortic aneurysms.
AB  - OBJECTIVES: The present study analyzes the early patency of intercostal artery
      reconstruction, using graft interposition and aortic patch anastomosis, and
      determines the fate of reattached intercostal arteries after repair of
      thoracoabdominal aortic aneurysms. METHODS: We selected 115 patients (mean age,
      63 +/- 15 years; range, 19-83 years; male, n = 83) treated by thoracoabdominal
      aortic aneurysm repair with 1 or more reconstructed intercostal arteries at the
      Kobe University Graduate School of Medicine between October 1999 and December
      2012. The intercostal arteries were reconstructed using graft interposition (n =
      66), aortic patch anastomosis (n = 42), or both (n = 7). RESULTS: The hospital
      mortality rate was 7.8% (n = 9). Eleven patients (9.6%) developed spinal cord
      ischemic injury (permanent, n = 6, transient, n = 5). The average number of
      reconstructed intercostal arteries per patient was 3.0 +/- 1.5 (1-7), and 345
      intercostal arteries were reattached. The overall patency rate was 74.2%
      (256/345) and that of aortic patch anastomosis was significantly better than that
      of graft interposition (90.8% [109/120] vs 65.3% [147/225], P < .01), but
      significantly worse for patients with than without spinal cord ischemic injury
      (51.9% [14/27] vs 76.1% [242/318], P = .01). There was no patch aneurysm in graft
      interposition during a mean of 49 +/- 38 (range, 2-147) postoperative months, but
      aortic patch anastomosis including 4 intercostal arteries became dilated in 2
      patients. CONCLUSIONS: Aortic patch anastomosis might offer better patency rates
      and prevent spinal cord ischemic injury compared with graft interposition.
      Although aneurysmal changes in intercostal artery reconstructions are rare, large
      blocks of aortic wall reconstruction should be closely monitored.

PMID- 24035378
TI  - Hypogammaglobulinemia after cardiopulmonary bypass in infants.
AB  - BACKGROUND: Hypogammaglobulinemia has been reported after cardiac surgery and may
      be associated with adverse outcomes. We sought to define baseline immunoglobulin
      (Ig) concentration in neonates and infants with congenital heart disease,
      determine their course after cardiopulmonary bypass (CPB), and determine if post
      CPB hypogammaglobulinemia was associated with increased morbidity. METHODS: This
      was a single-center, retrospective analysis of infants who underwent cardiac
      surgery with CPB between June 2010 and December 2011. The Ig concentration was
      obtained from banked plasma of 47 patients from a prior study (pre-CPB,
      immediately post-CPB, and 24 and 48 hours post-CPB). In addition, any Ig levels
      drawn for clinical purposes after CPB were included. Ig levels were excluded if
      drawn after chylothorax diagnosis or intravenous IgG administration. RESULTS: The
      median age was 7 days. Preoperative Ig concentration was similar to that
      described in healthy children. IgG level decreased to less than 50% of
      preoperative concentration by 24-hour post-CPB and failed to recover by 7 days.
      Of 47 patients, 25 (53%) had low IgG (<248 mg/dL) after CPB. Despite no
      difference in demographics or risk factors between patients with low and normal
      IgG, low IgG patients had more positive fluid balance at 24 hours and increased
      proinflammatory plasma cytokine levels, duration of mechanical ventilation, and
      cardiac intensive care unit length of stay. In addition, low IgG patients had an
      increased incidence of postoperative infections (40% vs 14%; P = .056).
      CONCLUSIONS: Hypogammaglobulinemia occurs in half of infants after CPB. Its
      association with fluid overload and increased inflammatory cytokines suggests it
      may result from capillary leak. Postoperative hypogammaglobulinemia is associated
      with increased morbidity, including more secondary infections.

PMID- 24035379
TI  - Dexmedetomidine, an alpha-2a adrenergic agonist, promotes ischemic tolerance in a
      murine model of spinal cord ischemia-reperfusion.
AB  - OBJECTIVE: Dexmedetomidine, an alpha-2a adrenergic agonist, given pre- and
      postoperatively was previously shown to attenuate neuronal injury in a murine
      model of spinal cord ischemia-reperfusion. In the brain, alpha-2 agonists have
      been shown to induce the phosphorylation of cyclic AMP response-element binding
      protein (CREB), a transcription factor necessary for neuron survival. We
      hypothesized that the alpha-2a adrenergic agonist given preoperatively increases
      CREB-mediated neuroprotective proteins, attenuating neuronal injury and
      cytoarchitectural decay. METHODS: Mice (ie, C57BL/6 mice) underwent 5 minutes of
      aortic occlusion via median sternotomy. Mice received 25 MUg/kg dexmedetomidine
      or equivalent normal saline at 24 hours, 12 hours, and 30 minutes preoperatively.
      Functional outcomes were recorded at 6 to 48 hours postoperatively when spinal
      cords were removed for histologic analysis. Spinal cords were examined for
      protein kinase B, CREB, B-cell lymphoma 2, and brain-derived neurotrophic factor
      following treatment alone or ischemia-reperfusion surgery. RESULTS: Following
      aortic occlusion, mice in the treatment group had preserved neurologic function
      at all time points (P < .05). Histologic analysis showed preserved
      cytoarchitecture and decreased neuronal injury in the treatment group when
      compared with ischemic controls. Additionally, analysis of spinal cord homogenate
      following surgery and pretreatment revealed a significant (P < .05) increase in B
      cell lymphoma 2 and brain-derived neurotrophic factor expression and protein
      kinase B and CREB phosphorylation with alpha-2a adrenergic agonist pretreatment.
      CONCLUSIONS: Pretreatment with the alpha-2a agonist dexmedetomidine preserved
      neurologic function and attenuated neuronal injury following thoracic aortic
      occlusion in mice. This relationship was associated with an increased
      phosphorylation of protein kinase B and CREB and subsequent up-regulation of
      antiapoptotic factor B-cell lymphoma 2 and brain-derived neurotrophic factor.
      Thus, alpha-2a receptor agonism-induced CREB phosphorylation and contributes to
      dexmedetomidine's protective mechanism in the spinal cord following ischemia.

PMID- 24035380
TI  - Regression of coronary disease after bypass surgery: Urban myth or common
      finding?
AB  - OBJECTIVES: Coronary artery disease has been viewed as a relentless, progressive
      disease. We sought to describe the prevalence and distribution of regression of
      native vessel disease in coronary artery bypass patients and characterize its
      relationship with bypass grafting. METHODS: Among 619 patients who underwent
      bypass surgery in a radial artery trial, 405 had follow-up angiography available
      a mean of 6.2 +/- 3.1 years (range, 0-14) after surgery. The percentage of
      diameter stenosis of each major native coronary vessel was reported by 3 cardiac
      specialists and classified into grades of nonflow limiting (0%-39%), moderate
      (40%-69%), flow limiting (70%-80%), severely stenosed (81%-99%), and occluded
      (100%). Native vessel disease regression was defined as decrease in 1 or more
      grades of stenosis between the pre- and postoperative angiograms. RESULTS: A
      total of 1742 native coronary arteries had preoperative stenosis of at least 40%
      and were included in the present analysis, receiving 753 arterial grafts and 391
      saphenous vein grafts. Overall, the prevalence of disease regression was 19.7%,
      and 45% of patients demonstrated regression in 1 or more vessels. The presence of
      an arterial graft increased the likelihood of disease regression (21.3% compared
      with 16% for venous bypassed vessels, P = .012) as did the location in the left
      circulation (22.6% compared with 13.9% for the right circulation, P < .001) and
      having a flow-limiting (>=70%) lesion (21.9% compared with 9.8% for moderate
      lesions, P < .001). CONCLUSIONS: Native coronary artery disease regression after
      coronary artery bypass grafting is common and affected by conduit type, vessel
      location, and lesion severity. Surgeons must consider these factors when
      assessing the requirement for bypass grafts in a borderline lesion.

PMID- 24035381
TI  - Open total aortic arch reconstruction for patients with advanced age in the era
      of endovascular repair.
AB  - BACKGROUND: The aim of this study is to evaluate the influence of advanced age on
      the postoperative course in open aortic arch repair using hypothermic circulatory
      arrest and selective antegrade cerebral perfusion. METHODS: Of 158 consecutive
      patients who underwent open total arch repair between 2008 and 2012, we
      retrospectively compared outcomes between octogenarians (group E: mean age, 83.0
      +/- 3.1 years [n = 40]) and their younger counterparts (group Y: mean age, 68.2
      +/- 10.2 years [n = 118]), and evaluated risk factors for an adverse
      postoperative course. RESULTS: The overall 30-day mortality was 7.0% (11/158),
      and by excluding 54 emergent cases, 30-day mortality was 4.8% (5/104). Ruptured
      cases were significantly observed in group E (17.5% [7/40] vs 3.4% [4/118]; P =
      .006). There were no significant differences in postoperative early results,
      including neurologic adverse events (12.5% [5/40] vs 6.8% [8/118]; P = .317) and
      30-day death (12.5% [5/40] vs 5.1% [6/118]; P = .147) between groups E and Y.
      Multivariate logistic analysis revealed rupture, preoperative consciousness
      disorder, and extended circulatory arrest time (>=67 minutes) were risk factors
      for serious complications (neurologic adverse events and 30-day death) (odds
      ratio [OR], 10.9 [P = .010]; OR, 5.2 [P = .040]; and OR, 3.5 [P = .028],
      respectively). A ruptured aorta was detected as an independent predictor of
      postoperative extended intensive care unit and hospital stay by multivariate
      linear regression analysis (P = .001 and P = .007, respectively). CONCLUSIONS:
      Advanced age was not associated with serious postoperative complications and
      adverse postoperative course.

PMID- 24035382
TI  - Left and right ventricular performance after arterial switch operation.
AB  - OBJECTIVE: Recent descriptions of decreased exercise capacity 10 to 15 years
      after arterial switch operation (ASO) suggest subclinical hemodynamic
      restrictions. Persistent impairment of ventricular performance following ASO may
      add to this. We aimed to characterize the time course of changes in biventricular
      performance within the first year following ASO. METHODS: We prospectively
      included 26 patients with transposition of the great arteries undergoing ASO and
      20 age-matched controls. Left and right ventricular systolic and diastolic
      performance was assessed using tissue Doppler imaging-derived peak systolic
      velocity, peak diastolic velocity, and peak early wave Doppler flow
      velocity/early diastolic tissue Doppler imaging velocity as well as mitral and
      tricuspid annular plane systolic excursion. Furthermore, left ventricular
      longitudinal, radial, and circumferential strain were assessed using speckle
      tracking strain imaging. Studies were performed preoperatively, 1 day
      postoperatively, at discharge, and at medium-term follow-up (9 months
      [interquartile range, 6-23 months] postoperatively). RESULTS: After an initial
      decrease in biventricular systolic and diastolic performance 1 day
      postoperatively versus preoperatively, recovery was observed in all parameters
      during medium-term follow-up. At medium-term follow-up left ventricular systolic
      and diastolic performance parameters were comparable in patients and controls. In
      contrast, right ventricular systolic and diastolic performance were still
      impaired in patients versus controls roughly 1 year postoperatively (tricuspid
      annular plane systolic excursion, 11.6 +/- 2.2 vs 18.6 +/- 3.1 mm; right
      ventricular peak systolic velocity, 8.1 +/- 2.3 vs 12.6 +/- 1.8 cm/second; right
      ventricular peak diastolic velocity, 12.4 +/- 3.0 vs 18.2 +/- 4.2 cm/second; and
      right ventricular peak early wave Doppler flow velocity/early diastolic tissue
      Doppler imaging velocity, 6.7 +/- 2.1 vs 4.3 +/- 1.3; all Ps < .001).
      CONCLUSIONS: If early ASO is performed, left ventricular performance recovers to
      control values within the first postoperative year. In contrast, right
      ventricular systolic and diastolic performance remained impaired during follow
      up, which stresses the importance of postoperative follow-up of right ventricular
      performance.

PMID- 24035383
TI  - Molecular detection of gastrointestinal viral infections in hospitalized
      patients.
AB  - Gastrointestinal viral syndromes are a common cause of morbidity and mortality in
      humans worldwide. Etiological agents include a large number of viruses
      encompassing several orders, families, and genera. During the period April 2011
      to April 2012, 689 stool samples from as many patients hospitalized at the
      Fondazione IRCCS Policlinico San Matteo of Pavia exhibiting gastrointestinal
      syndromes were examined for the presence of rotavirus, norovirus, astrovirus,
      adenovirus, rhinovirus, enterovirus, parechovirus, bocavirus, coronavirus,
      sapovirus, cosavirus, and aichi virus using polymerase chain reaction assays.
      Gastrointestinal viral agents were detected in 246 (36%) patients of the 689
      analyzed. Adenovirus and norovirus were the most common viruses in this cohort,
      while aichi virus was the only gastrointestinal agent not detected. Surprisingly,
      rhinovirus was one of the most frequently detected viruses. However, a potential
      association with gastroenteritis remains to be confirmed. 

PMID- 24035384
TI  - Interpretation of positive molecular tests of common viruses in the cerebrospinal
      fluid.
AB  - Many central nervous system infections are historically difficult to diagnose.
      Polymerase chain reaction (PCR) has revolutionized the diagnosis of these
      infections because of their high sensitivity despite the lack of data on clinical
      usefulness. We conducted a retrospective study that included patients with
      positive cerebrospinal fluid (CSF) PCR for herpes simplex virus, varicella-zoster
      virus, JC virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) between
      January 2009 and December 2011. The positive results were grouped into definite,
      likely, and possible true positives and likely false-positive categories based on
      pre-specified definitions specific to each virus. Of 1663 CSF viral PCR tests, 88
      were positive (5%). The combined positive predictive value (PPV) was 58%. The
      PPVs were least for CMV and EBV at 29 and 37%, respectively. A positive CSF viral
      PCR result has to be interpreted with caution due to several false-positive
      results. 

PMID- 24035385
TI  - [Undergraduate surgical research].

PMID- 24035386
TI  - [Implementation of a diabetes disease management program in Switzerland:
      patients' and healthcare professionals' point of view].
AB  - BACKGROUND: A reorganization of healthcare systems is required to meet the
      challenge of the increasing prevalence of chronic diseases, e.g. diabetes. In
      North-America and Europe, several countries have thus developed national or
      regional chronic disease management programs. In Switzerland, such initiatives
      have only emerged recently. In 2010, the canton of Vaud set up the "Diabetes
      Cantonal Program", within the framework of which we conducted a study designed to
      ascertain the opinions of both diabetic patients and healthcare professionals on
      the elements that could be integrated into this program, the barriers and
      facilitators to its development, and the incentives that could motivate these
      actors to participate. METHODS: We organized eight focus-groups: one with
      diabetic patients and one with healthcare professionals in the four sanitary
      areas of the canton of Vaud. The discussions were recorded, transcribed and
      submitted to a thematic content analysis. RESULTS: Patients and healthcare
      professionals were rather in favour of the implementation of a cantonal program,
      although patients were more cautious concerning its necessity. All participants
      envisioned a set of elements that could be integrated to this program. They also
      considered that the program could be developed more easily if it were adapted to
      patients' and professionals' needs and if it used existing structures and
      professionals. The difficulty to motivate both patients and professionals to
      participate was mentioned as a barrier to the development of this program
      however. Quality or financial incentives could therefore be created to overcome
      this potential problem. CONCLUSION: The identification of the elements to
      consider, barriers, facilitators and incentives to participate to a chronic
      disease management program, obtained by exploring the opinions of patients and
      healthcare professionals, should favour its further development and
      implementation.

PMID- 24035387
TI  - LRRC45 is a centrosome linker component required for centrosome cohesion.
AB  - During interphase, centrosomes are connected by a proteinaceous linker between
      the proximal ends of the centrioles, which is important for the centrosomes to
      function as a single microtubule-organizing center. However, the composition and
      regulation of centrosomal linker remain largely unknown. Here, we show that
      LRRC45 is a centrosome linker that localizes at the proximal ends of the
      centrioles and forms fiber-like structures between them. Depletion of LRRC45
      results in centrosome splitting during interphase. Moreover, LRRC45 interacts
      with both C-Nap1 and rootletin and is phosphorylated by Nek2A at S661 during
      mitosis. After phosphorylation, both LRRC45 centrosomal localization and fiber
      like structures are significantly reduced, which subsequently leads to centrosome
      separation. Thus, LRRC45 is a critical component of the proteinaceous linker
      between two centrioles and is required for centrosome cohesion. 

PMID- 24035388
TI  - RAB8B is required for activity and caveolar endocytosis of LRP6.
AB  - Wnt/beta-catenin signaling plays an important role in embryonic development and
      adult tissue homeostasis. When Wnt ligands bind to the receptor complex, LRP5/6
      coreceptors are activated by phosphorylation and concomitantly endocytosed. In
      vertebrates, Wnt ligands induce caveolin-dependent endocytosis of LRP6 to relay
      signal downstream, whereas antagonists such as Dickkopf promote clathrin
      dependent endocytosis, leading to inhibition. However, little is known about how
      LRP6 is directed to different internalization mechanisms, and how caveolin
      dependent endocytosis is mediated. In an RNAi screen, we identified the Rab
      GTPase RAB8B as being required for Wnt/beta-catenin signaling. RAB8B depletion
      reduces LRP6 activity, beta-catenin accumulation, and induction of Wnt target
      genes, whereas RAB8B overexpression promotes LRP6 activity and internalization
      and rescues inhibition of caveolar endocytosis. In Xenopus laevis and Danio
      rerio, RAB8B morphants show lower Wnt activity during embryonic development. Our
      results implicate RAB8B as an essential evolutionary conserved component of
      Wnt/beta-catenin signaling through regulation of LRP6 activity and endocytosis.

PMID- 24035389
TI  - Nkx6.1 is essential for maintaining the functional state of pancreatic beta
      cells.
AB  - Recently, loss of beta-cell-specific traits has been proposed as an early cause
      of beta cell failure in diabetes. However, the molecular mechanisms that underlie
      the loss of beta cell features remain unclear. Here, we identify an Nkx6.1
      controlled gene regulatory network as essential for maintaining the functional
      and molecular traits of mature beta cells. Conditional Nkx6.1 inactivation in
      adult mice caused rapid-onset diabetes and hypoinsulinemia. Genome-wide analysis
      of Nkx6.1-regulated genes and functional assays further revealed a critical role
      for Nkx6.1 in the control of insulin biosynthesis, insulin secretion, and beta
      cell proliferation. Over time, Nkx6.1-deficient beta cells acquired molecular
      characteristics of delta cells, revealing a molecular link between impaired beta
      cell functional properties and loss of cell identity. Given that Nkx6.1 levels
      are reduced in human type 2 diabetic beta cells, our study lends support to the
      concept that loss of beta cell features could contribute to the pathogenesis of
      diabetes. 

PMID- 24035390
TI  - Misregulation of an adaptive metabolic response contributes to the age-related
      disruption of lipid homeostasis in Drosophila.
AB  - Loss of metabolic homeostasis is a hallmark of aging and is commonly
      characterized by the deregulation of adaptive signaling interactions that
      coordinate energy metabolism with dietary changes. The mechanisms driving age
      related changes in these adaptive responses remain unclear. Here, we characterize
      the deregulation of an adaptive metabolic response and the development of
      metabolic dysfunction in the aging intestine of Drosophila. We find that
      activation of the insulin-responsive transcription factor Foxo in intestinal
      enterocytes is required to inhibit the expression of evolutionarily conserved
      lipases as part of a metabolic response to dietary changes. This adaptive
      mechanism becomes chronically activated in the aging intestine, mediated by
      changes in Jun-N-terminal kinase (JNK) signaling. Age-related chronic JNK/Foxo
      activation in enterocytes is deleterious, leading to sustained repression of
      intestinal lipase expression and the disruption of lipid homeostasis. Changes in
      the regulation of Foxo-mediated adaptive responses thus contribute to the age
      associated breakdown of metabolic homeostasis. 

PMID- 24035391
TI  - Genomic analysis of hESC pedigrees identifies de novo mutations and enables
      determination of the timing and origin of mutational events.
AB  - Given the association between mutational load and cancer, the observation that
      genetic aberrations are frequently found in human pluripotent stem cells (hPSCs)
      is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs)
      have shown that deletions and regions of loss of heterozygosity (LOH) tend to
      arise during reprogramming and early culture, whereas duplications more
      frequently occur during long-term culture. For the corresponding experiments in
      human embryonic stem cells (hESCs), we studied two sets of hESC lines: one
      including the corresponding parental DNA and the other generated from single
      blastomeres from four sibling embryos. Here, we show that genetic aberrations
      observed in hESCs can originate during preimplantation embryo development and/or
      early derivation. These early aberrations are mainly deletions and LOH, whereas
      aberrations arising during long-term culture of hESCs are more frequently
      duplications. Our results highlight the importance of close monitoring of genomic
      integrity and the development of improved methods for derivation and culture of
      hPSCs. 

PMID- 24035392
TI  - Wnt signaling is required for long-term memory formation.
AB  - Wnt signaling regulates synaptic plasticity and neurogenesis in the adult nervous
      system, suggesting a potential role in behavioral processes. Here, we probed the
      requirement for Wnt signaling during olfactory memory formation in Drosophila
      using an inducible RNAi approach. Interfering with beta-catenin expression in
      adult mushroom body neurons specifically impaired long-term memory (LTM) without
      altering short-term memory. The impairment was reversible, being rescued by
      expression of a wild-type beta-catenin transgene, and correlated with disruption
      of a cellular LTM trace. Inhibition of wingless, a Wnt ligand, and arrow, a Wnt
      coreceptor, also impaired LTM. Wingless expression in wild-type flies was
      transiently elevated in the brain after LTM conditioning. Thus, inhibiting three
      key components of the Wnt signaling pathway in adult mushroom bodies impairs LTM,
      indicating that this pathway mechanistically underlies this specific form of
      memory. 

PMID- 24035393
TI  - Live-cell visualization of pre-mRNA splicing with single-molecule sensitivity.
AB  - Removal of introns from pre-messenger RNAs (pre-mRNAs) via splicing provides a
      versatile means of genetic regulation that is often disrupted in human diseases.
      To decipher how splicing occurs in real time, we directly examined with single
      molecule sensitivity the kinetics of intron excision from pre-mRNA in the nucleus
      of living human cells. By using two different RNA labeling methods, MS2 and
      lambdaN, we show that beta-globin introns are transcribed and excised in 20-30 s.
      Furthermore, we show that replacing the weak polypyrimidine (Py) tract in mouse
      immunoglobulin MU (IgM) pre-mRNA by a U-rich Py decreases the intron lifetime,
      thus providing direct evidence that splice-site strength influences splicing
      kinetics. We also found that RNA polymerase II transcribes at elongation rates
      ranging between 3 and 6 kb min(-1) and that transcription can be rate limiting
      for splicing. These results have important implications for a mechanistic
      understanding of cotranscriptional splicing regulation in the live-cell context.

PMID- 24035394
TI  - Nf1 loss and Ras hyperactivation in oligodendrocytes induce NOS-driven defects in
      myelin and vasculature.
AB  - Patients with neurofibromatosis type 1 (NF1) and Costello syndrome Rasopathy have
      behavioral deficits. In NF1 patients, these may correlate with white matter
      enlargement and aberrant myelin. To model these features, we induced Nf1 loss or
      HRas hyperactivation in mouse oligodendrocytes. Enlarged brain white matter
      tracts correlated with myelin decompaction, downregulation of claudin-11, and
      mislocalization of connexin-32. Surprisingly, non-cell-autonomous defects in
      perivascular astrocytes and the blood-brain barrier (BBB) developed, implicating
      a soluble mediator. Nitric oxide (NO) can disrupt tight junctions and gap
      junctions, and NO and NO synthases (NOS1-NOS3) were upregulated in mutant white
      matter. Treating mice with the NOS inhibitor NG-nitro-L-arginine methyl ester or
      the antioxidant N-acetyl cysteine corrected cellular phenotypes. CNP-HRasG12V
      mice also displayed locomotor hyperactivity, which could be rescued by
      antioxidant treatment. We conclude that Nf1/Ras regulates oligodendrocyte NOS and
      that dysregulated NO signaling in oligodendrocytes can alter the surrounding
      vasculature. The data suggest that antioxidants may improve some behavioral
      deficits in Rasopathy patients.

PMID- 24035395
TI  - Integration of multiple nutrient cues and regulation of lifespan by ribosomal
      transcription factor Ifh1.
AB  - Ribosome biogenesis requires an enormous commitment of energy and resources in
      growing cells. In budding yeast, the transcriptional coactivator Ifh1p is an
      essential regulator of ribosomal protein (RP) gene transcription. Here, we report
      that Ifh1p is dynamically acetylated and phosphorylated as a function of the
      growth state of cells. Ifh1p is acetylated at numerous sites in its N-terminal
      region by Gcn5p and deacetylated by NAD(+)-dependent deacetylases of the sirtuin
      family. Acetylation of Ifh1p is responsive to intracellular acetyl-CoA levels and
      serves to regulate the stability of Ifh1p. The phosphorylation of Ifh1p is
      mediated by protein kinase A and is dependent on TORC1 signaling. Thus, multiple
      nutrient-sensing mechanisms converge on Ifh1p. However, instead of modulating
      overall rates of RP gene transcription or cell growth, the nutrient-responsive
      phosphorylation of Ifh1p plays a more prominent role in the regulation of
      cellular replicative lifespan. 

PMID- 24035397
TI  - The behavior patterns of abused children as described in their testimonies.
AB  - The aim of the current study is to identify how children describe their behavior
      during abuse and to explore their behavior further with respect to the type of
      the abuse (physical or sexual), frequency of abuse (single or multiple
      incidents), familiarity with the suspect, and children's age and gender, with the
      assumption that this information may have a significant effect on the children's
      recovery process. The study involved 224 transcripts of interviews with alleged
      victims aged 5-14 in Israel. The sample was randomly selected from all of the
      forensic investigations with children that were conducted in Israel in 2011. The
      results show that abuse type has a strong effect on children's behavior, with
      children in the sexual abuse group reporting more fight and flight behavior and
      children in the physical abuse group reporting more self-change behavior. This
      finding was interacted with the severity of abuse variable, with children in the
      sexual abuse group reporting less flight behavior and an increase in the self
      change behavior with the highest level of severity of abuse (touch under the
      clothes and penetration). Investigative interviews with children can be a
      significant source of information for practitioners within the clinical context.
      The current study stresses the consequences that abuse can have on children's
      behavior during these incidents and the implications for the therapy process with
      the children. 

PMID- 24035398
TI  - Opinions of UK perinatal health care professionals on home birth.
AB  - OBJECTIVE: to evaluate the opinions of UK perinatal health care professionals on
      home birthing. DESIGN: cross-sectional survey. SETTING: four hospitals and three
      Primary Care Trusts in the East of England. POPULATION: hospital and community
      midwives, GPs, consultant obstetricians and gynaecologists, consultant
      paediatricians and neonatologists. METHODS: postal questionnaire between December
      2010 and June 2011 using Likert scales (range 0-10) and freetext questions. Data
      were analysed using the Kruskal-Wallis test and qualitative methods. MAIN OUTCOME
      MEASURES: opinions, support and enthusiasm for home birthing. FINDINGS: 432/831
      (52%) professionals responded: 224/418 (54%) midwives, 148/321 (46%) GPs, 32/52
      (62%) obstetricians/gynaecologists and 28/41 (68%) paediatricians/neonatologists.
      Midwives were more enthusiastic about home birthing than any other professionals
      (median Likert scale rating: 9 [IQR 8-10], p<0.0001) and more supportive of the
      UK government's plan to increase home birth rates (median 8.5 [IQR 7-10],
      p<0.0001). GPs and obstetricians/gynaecologists tended to hold neutral opinions
      about home birthing (median of GPs 5 [IQR 3-7.5] and of
      obstetrician/gynaecologists 5 [IQR 2-7]) and regarding support for the
      government's plan (GP median 5 [IQR 2-6]; obstetrician/gynaecologists median 5
      [IQR 2-5]). Paediatricians/neonatologists were generally negative about home
      birthing (median 4 [IQR 3-5]) and opposed to the government's plan (median 3 [IQR
      2-5]). CONCLUSIONS: significant differences of opinion exist between UK perinatal
      health care professional groups about home birthing. Negative and neutral
      opinions should be further explored and addressed as they may impact on the
      uptake of home birth by women.

PMID- 24035396
TI  - Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Goutieres syndrome
      related SAMHD1.
AB  - Long interspersed elements 1 (LINE-1) occupy at least 17% of the human genome and
      are its only active autonomous retrotransposons. However, the host factors that
      regulate LINE-1 retrotransposition are not fully understood. Here, we demonstrate
      that the Aicardi-Goutieres syndrome gene product SAMHD1, recently revealed to be
      an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and
      neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and
      LINE-1-mediated Alu/SVA retrotransposition. We also found that mutant SAMHD1s of
      Aicardi-Goutieres syndrome patients are defective in LINE-1 inhibition. Several
      domains of SAMHD1 are critical for LINE-1 regulation. SAMHD1 inhibits LINE-1
      retrotransposition in dividing cells. An enzymatic active site mutant SAMHD1
      maintained substantial anti-LINE-1 activity. SAMHD1 inhibits ORF2p-mediated LINE
      1 reverse transcription in isolated LINE-1 ribonucleoproteins by reducing ORF2p
      level. Thus, SAMHD1 may be a cellular regulator of LINE-1 activity that is
      conserved in mammals. 

PMID- 24035399
TI  - The impact of peer support in the context of perinatal mental illness: a meta
      ethnography.
AB  - OBJECTIVE: this paper is a report of a systematic review and meta-ethnography to
      explore the impact of peer support in the context of perinatal mental illness
      (PMI). METHOD: systematic review methods identified five qualitative studies
      about women's experiences of PMI, and the impact peer support has on their
      journey towards emotional well-being. Findings from the identified studies were
      synthesised into themes, using meta-ethnography. SYNTHESIS AND FINDINGS: the meta
      ethnography produced four themes; 'Isolation: the role of peer support', 'Seeking
      validation through peer support', 'The importance of social norms of motherhood',
      and 'Finding affirmation/a way forward; the impact of peer support'. These themes
      represent women's experiences of PMI, their encounters with peer support groups
      within that context, and the impact of such encounters on their mental health
      status. KEY CONCLUSION: recognising the risk of isolation and having pathways of
      referral to peer support networks is important, as are practitioners roles in
      nurturing peer support networks in perinatal care. More research is required to
      establish the most successful formats/structures of peer support. Practitioners
      should also recognise their individual and collective professional duty to
      challenge stereotypical depictions of motherhood wherever they arise, as this
      'gold standard' benchmark of good mothering engenders guilt about not being good
      enough, often leaving women feeling inadequate. IMPLICATIONS FOR PRACTICE:
      isolation is a key factor in PMI. Practitioners should be instrumental in their
      acceptance and development of peer support for PMI, ensuring these networks are
      valued, nurtured and encouraged. This study illustrates the powerful effect of
      professional and social forces on how new mothers feel about themselves.

PMID- 24035400
TI  - Establishing functional residual capacity in the non-breathing infant.
AB  - The transition to newborn life critically depends upon lung aeration and the
      onset of air-breathing, which triggers major cardiovascular changes required for
      postnatal life, including increases in pulmonary blood flow. Recent imaging
      studies indicate that lung aeration and functional residual capacity (FRC)
      recruitment results from inspiratory efforts, which create transpulmonary
      pressure gradients. During inspiration, these pressure gradients drive airway
      liquid movement through the conducting and into the distal airways where it
      crosses the pulmonary epithelium and enters the surrounding tissue. Although this
      process can occur rapidly (within 3-5 breaths), liquid clearance from lung tissue
      is much slower, resulting in oedema and increased interstitial tissue pressures,
      facilitating liquid re-entry into the airways at FRC. Whereas this liquid may be
      cleared during the next inspiration, liquid re-entry at FRC can be opposed by
      Na(+) reabsorption, oncotic pressures and expiratory braking manoeuvres.
      Recognition that transpulmonary pressure gradients mainly drive airway liquid
      clearance at birth has provided a clearer understanding of how this process may
      be facilitated in very preterm infants. In particular, it underpins the rationale
      for providing respiratory support that initially focuses on moving liquid through
      tubes (airways) rather than air. As the viscosity of liquid is much greater than
      air, the resistance to moving liquid is ~ 100 times greater than air,
      necessitating the use of higher pressures or longer inflation times. Although it
      is unclear how this strategy could be safely applied clinically, it is clear that
      end-expiratory pressures are required to create and maintain FRC in preterm
      infants.

PMID- 24035401
TI  - Infant sleep problems: a qualitative analysis of first-time mothers' coping
      experience.
AB  - OBJECTIVE: to describe the aspects of infant sleep perceived as problematic by
      first-time Taiwanese mothers and to discover how mothers cope in response to
      infant sleep concerns. DESIGN: a qualitative approach was used for data
      collection. SETTING: in-depth interviews were conducted and audio-taped at
      mothers' homes. PARTICIPANTS: 12 first-time mothers within three months post
      partum. MEASUREMENT AND FINDINGS: content analysis was performed to identify
      patterns, similarities, and differences in the individual and collective
      interview data. The major themes describing maternal coping experiences were
      'self-help' and 'seek-help.' Self-help coping efforts included reception and
      acceptance of suggestions as well as changing behaviour to allow mothers to feel
      capable of adapting to infant sleep patterns or problems. Seek-help was a later
      stage of coping for mothers when they actively utilised formal and informal
      sources of help to identify and manage infant sleep problems. The majority of
      mothers sought informal help sources from family members, friends, or online
      information. Mothers who suspected their infant of suffering from sleep problems
      either delayed seeking medical advice or did not actively consult a health care
      provider. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: nurses and health care
      providers who work in antenatal, postnatal, and paediatric clinics should
      actively educate and provide information about infant sleep patterns and sleep
      management options to first-time mothers and discuss maternal coping strategies.

PMID- 24035402
TI  - Computer-assisted cognitive remediation therapy: cognition, self-esteem and
      quality of life in schizophrenia.
AB  - BACKGROUND: Quality of life (QoL) is an important outcome in the treatment of
      schizophrenia. Cognitive deficits have an impact on functional outcomes.
      Cognitive remediation therapy is emerging as a psychological intervention that
      targets cognitive impairment, but the effect of computer-assisted cognitive
      remediation on neuropsychology and social functioning and wellbeing remains
      unclear. The aim of the current study is to investigate the neurocognitive
      outcomes of computer-assisted cognitive remediation (CACR) therapy in a sample of
      schizophrenia patients, and to measure the quality of life and self-esteem as
      secondary outcomes. METHODS: Sixty-seven people with schizophrenia were randomly
      assigned to computer-assisted cognitive remediation or an active control
      condition. The main outcomes were neuropsychological measures and secondary
      outcomes (self-esteem and quality of life). Measurements were recorded at
      baseline and post-treatment. RESULTS: The CACR therapy group improved in speed of
      processing, working memory and reasoning and problem-solving cognitive domains.
      QoL and self-esteem measures also showed significant improvements over time in
      this group. CONCLUSIONS: Computer-assisted cognitive remediation therapy for
      people with schizophrenia achieved improvements in neuropsychological performance
      and in QoL and self-esteem measurements.

PMID- 24035403
TI  - Pomaglumetad methionil: no significant difference as an adjunctive treatment for
      patients with prominent negative symptoms of schizophrenia compared to placebo.
AB  - This study tested whether treatment with pomaglumetad methionil (LY2140023
      monohydrate), a metabotropic glutamate receptor 2/3 agonist compared with placebo
      (PBO), when added to a fixed-dose second-generation antipsychotic (SGA)
      demonstrated significantly greater reduction of negative symptoms, as assessed by
      the 16-item Negative Symptom Assessment scale (NSA-16), in patients with
      schizophrenia. This parallel-group, 16-week study enrolled adults with
      schizophrenia who were receiving standard of care (SOC) therapy, which included
      >=3months treatment with one of four SGAs: aripiprazole, olanzapine, risperidone,
      or quetiapine. Patients received either 20mg of twice daily LY2140023 monohydrate
      (LY2140023) or concurrent PBO SGA. The primary efficacy measure was change from
      baseline to final visit in NSA-16 total score. Secondary measures included
      additional measures of efficacy, cognition, and assessments of safety. Of 352
      patients screened, 167 were randomly assigned to treatment, and 110 patients
      completed the study. Patients treated with LY2140023 and SOC failed to
      demonstrate a statistically significant improvement over patients treated with
      PBO and SOC on NSA-16 total score at endpoint or at any point during the study
      (all p>0.131). Changes in secondary efficacy measures were not significantly
      different between groups at endpoint. With the exception of vomiting which was
      greater in the LY2140023 group, there were no statistically significant
      differences in safety and tolerability measures. This study found no benefit of
      adjunctive LY2140023 versus PBO for negative symptoms in patients with
      schizophrenia receiving treatment with SOC. LY2140023 was generally well
      tolerated in these patients. 

PMID- 24035404
TI  - Altered asymmetry of the anterior cingulate cortex in subjects at genetic high
      risk for psychosis.
AB  - OBJECTIVE: Many studies have reported that patients with schizophrenia often have
      structural abnormalities of the anterior cingulate cortex (ACC) and that some of
      these seem to be of genetic origin, therefore predating the onset of illness. The
      present study aimed to investigate whether these alterations in the ACC are
      genetic in origin by comparing the morphological patterns of three groups: normal
      controls, subjects at genetic high risk (GHR) for psychosis, and patients with
      schizophrenia. The relationships between morphological variations and executive
      function were also investigated. METHODS: This study examined the magnetic
      resonance images of cingulate sulcus/paracingulate sulcus (CS/PCS) folding
      patterns in 222 subjects (103 normal subjects, 30 individuals at GHR, and 89
      patients with schizophrenia) and evaluated differences in the morphological and
      asymmetrical patterns of the ACC among groups. Neurocognitive tests were then
      performed and differences in cognitive performance were analyzed according to
      morphological variation. RESULTS: Differences in PCS folding were detected; the
      control group was significantly more likely than were other groups to show a well
      developed left PCS (p=0.009) and leftward asymmetry of the PCS (p<0.001).
      However, neither GHR subjects (p=0.346) nor patients (p=0.784) showed this
      leftward asymmetry. No statistically significant differences in CS continuity
      were observed. A more prominent left PCS (p=0.031) and leftward PCS asymmetry
      (p=0.030) were both associated with higher scores on the working memory task.
      CONCLUSION: The results suggest that GHR subjects have distinct
      neurodevelopmental anomalies that resemble those of patients with schizophrenia
      even though they do not display any psychotic symptoms. Certain developmental
      alterations in the ACC, such as the loss of leftward sulcal asymmetry in patients
      with schizophrenia, might be related to genetic factors. Additionally, this
      morphological alteration might partly account for the impaired executive function
      in schizophrenia.

PMID- 24035406
TI  - Immunological checkpoint inhibitors enter adolescence.

PMID- 24035405
TI  - Tremelimumab for patients with chemotherapy-resistant advanced malignant
      mesothelioma: an open-label, single-arm, phase 2 trial.
AB  - BACKGROUND: Monoclonal antibodies to cytotoxic T-lymphocyte antigen 4 (CTLA4)
      have therapeutic activity in different tumour types. We aimed to investigate the
      efficacy, safety, and immunological activity of the anti-CTLA4 monoclonal
      antibody, tremelimumab, in advanced malignant mesothelioma. METHODS: In our open
      label, single-arm, phase 2 study, we enrolled patients aged 18 years or older
      with measurable, unresectable malignant mesothelioma and progressive disease
      after a first-line platinum-based regimen. Eligible patients had to have a life
      expectancy of 3 months or more, an Eastern Cooperative Oncology Group performance
      status of 2 or less, and no history of autoimmune disease. Patients received
      tremelimumab 15 mg/kg intravenously once every 90 days until progressive disease
      or severe toxicity. The primary endpoint was the proportion of patients who
      achieved an objective response (complete or partial response), with a target
      response rate of 17% according to the modified Response Evaluation Criteria in
      Solid Tumors (RECIST) for pleural malignant mesothelioma or standard RECIST 1.0
      for peritoneal malignant mesothelioma. Analyses were done according to intention
      to treat. This trial is registered with EudraCT, number 2008-005171-95, and
      ClinicalTrials.gov, number NCT01649024. FINDINGS: Between May 27, 2009, and Jan
      10, 2012, we enrolled 29 patients. All patients received at least one dose of
      tremelimumab (median two doses, range one to nine). No patients had a complete
      response and two patients (7%) had a durable partial response (one lasting 6
      months and one lasting 18 months); one partial response occurred after initial
      progressive disease. Thus, the study did not reach its primary endpoint. However,
      we noted disease control in nine (31%) patients and a median progression-free
      survival of 6.2 months (95% CI 1.3-11.1) and a median overall survival of 10.7
      months (0.0-21.9). 27 patients (93%) had at least one grade 1-2 treatment
      emergent adverse event (mainly cutaneous rash, pruritus, colitis, or diarrhoea),
      and four patients (14%) had at least one grade 3-4 treatment-emergent adverse
      event (two gastrointestinal, one neurological, two hepatic, and one pancreatic).
      INTERPRETATION: Although the effect size was small in our phase 2 trial,
      tremelimumab seemed to have encouraging clinical activity and an acceptable
      safety and tolerability profile in previously treated patients with advanced
      malignant mesothelioma. FUNDING: Associazione Italiana per la Ricerca sul Cancro,
      Istituto Toscano Tumori, Pfizer, and Fondazione Buzzi Unicem.

PMID- 24035407
TI  - Galantamine versus risperidone treatment of neuropsychiatric symptoms in patients
      with probable dementia: an open randomized trial.
AB  - OBJECTIVE: To examine the effects of galantamine and risperidone on
      neuropsychiatric symptoms in dementia (NPSD) and global function. METHODS: Using
      a randomized, controlled and open-blind, one-center trial at an in- and
      outpatient clinic at a university hospital, we studied 100 adults with probable
      dementia and NPSD. Participants received galantamine (N = 50, target dose 24 mg)
      or risperidone (N = 50, target dose 1.5 mg) for 12 weeks. The primary outcome was
      effects on NPSD assessed by the Neuropsychiatric Inventory (NPI). Secondary
      measures included the Mini-Mental State Examination (MMSE), Clinical Dementia
      Rating, Clinical Global Impression, and Simpson Angus scales. All tests were
      performed before and after treatment. RESULTS: Outcome measures were analyzed
      using analysis of covariance. Ninety-one patients (67% women, mean age 79 +/- 7.5
      years) with initial NPI score of 51.0 (+/- 25.8) and MMSE of 20.1 (+/- 4.6)
      completed the trial. Both galantamine and risperidone treatments resulted in
      improved NPSD symptoms and were equally effective in treating several NPI
      domains. However, risperidone showed a significant treatment advantage in the NPI
      domains irritation and agitation, F(1, 97) = 5.2, p = 0.02. Galantamine treatment
      also ameliorated cognitive functions where MMSE scores increased 2.8 points
      compared with baseline (95% confidence interval: 1.96-3.52). No treatment-related
      severe side effects occurred. CONCLUSIONS: These results support that
      galantamine, with its benign safety profile, can be used as first-line treatment
      of NPSD symptoms, unless symptoms of irritation and agitation are prominent,
      where risperidone is more efficient.

PMID- 24035408
TI  - Amniotic fluid embolism: a leading cause of maternal death yet still a medical
      conundrum.
AB  - Amniotic fluid embolism is a rare and potentially catastrophic condition that is
      unique to pregnancy. The presentation may range from relatively subtle clinical
      events to sudden maternal cardiac arrest. Despite an increased awareness of the
      condition, it remains a leading cause of maternal mortality. The underlying
      mechanisms of amniotic fluid embolism are poorly understood, but current theories
      support an immune-based mechanism which is triggered by potentially small amounts
      of amniotic fluid gaining access to the maternal circulation. This can result in
      a wide spectrum of clinical findings, with cardiovascular and haematological
      disturbances being prominent. The management of a suspected episode of amniotic
      fluid embolism is generally considered to be supportive, although in centres with
      specific expertise, echocardiography may assist in guiding management. Whilst
      outcomes after an episode of amniotic fluid embolism are still concerning,
      mortality would appear to have decreased in recent times, likely secondary to an
      improved awareness of the condition, advances in acute care and the inclusion of
      less severe episodes in case registries. 

PMID- 24035409
TI  - Analysis of ultrasonic waves propagating in a bone plate over a water half-space
      with and without overlying soft tissue.
AB  - Recent in vitro studies have shown that guided waves can characterize bone
      properties. However, for clinical applications to be viable, the soft-tissue
      layer should be considered. This study examined the effect of soft tissue on
      guided waves using a bovine bone plate over a water half-space and overlaid by a
      4-mm gelatin-based soft-tissue mimic. The data (with and without soft tissue)
      clearly show a high-frequency, fast-propagating wave packet and a low-frequency,
      delayed phase group. The presence of soft tissue attenuates the signals
      significantly and increases mode density and number as predicted by theory. The
      data retain higher frequency content than the bone-plate data at large offsets.
      Using theoretical dispersion curves, the guided modes can be identified with mode
      1 (similar to the A0 Lamb mode) minimally affected by the addition of soft
      tissue. There is infiltration of high-frequency, late-arriving energy within the
      low-velocity guided-wave regime. Results of travel-time calculation suggest that
      P-wave and PP-reflections/multiples within the soft tissue may be responsible for
      the high-frequency oscillations.

PMID- 24035410
TI  - A comparison of acoustic cavitation detection thresholds measured with piezo
      electric and fiber-optic hydrophone sensors.
AB  - A Fabry-Perot interferometer fiber-optic hydrophone (FOH) was investigated for
      use as an acoustic cavitation detector and compared with a piezo-ceramic passive
      cavitation detector (PCD). Both detectors were used to measure negative pressure
      thresholds for broadband emissions in 3% agar and ex vivo bovine liver
      simultaneously. FOH-detected half- and fourth-harmonic emissions were also
      studied. Three thresholds were defined and investigated: (i) onset of cavitation;
      (ii) 100% probability of cavitation; and (iii) a time-integrated threshold where
      broadband signals integrated over a 3-s exposure duration, averaged over 5-10
      repeat exposures, become statistically significantly greater than noise. The
      statistical sensitiviy of FOH broadband detection was low compared with that of
      the PCD (0.43/0.31 in agar/liver). FOH-detected fourth-harmonic data agreed best
      with PCD broadband (sensitivity: 0.95/0.94, specificity: 0.89/0.76 in
      agar/liver). The FOH has potential as a cavitation detector, particularly in
      applications where space is limited or during magnetic resonance-guided studies. 

PMID- 24035411
TI  - Ultrasound assessment of the entheses in primary Sjogren syndrome.
AB  - Although tendon pain is commonly reported in primary Sjogren syndrome (pSS), the
      underlying mechanism is unknown. The objective of this study was to determine
      whether tendon pain in pSS is related to involvement of the tendons and entheses.
      We performed a physical examination of 288 entheseal insertion sites in 16
      patients with active pSS and 162 entheseal insertion sites in 9 healthy controls
      without symptoms or medications. Then ultrasound was used to assess entheseal and
      tendon sites of these patients (n = 208) and controls (n = 117). Ultrasound was
      performed in B mode first to detect structural damages, and in power Doppler mode
      to detect blood flow abnormalities. By physical examination, 9 (56%) of the 16
      pSS patients had pain to palpation of fibromyalgia tender points, two of whom had
      more than 11 tender points. The number of positive points ranged from 2 to 18,
      with a mean of 8 +/- 6.0. None of the healthy controls had positive tender
      points. None had structural or blood-flow abnormalities by ultrasound. To
      conclude, this study provides the first data on ultrasound findings in patients
      with active pSS. Although 56% of patients had clinical tender points, none had
      structural or blood-flow abnormalities by ultrasound, suggesting the absence of
      inflammation of the tendons and entheses in this disease.

PMID- 24035412
TI  - Comparative study of cognitive-behavioral psychotherapy and nutritional support
      in patients with different types of eating disorders.
AB  - BACKGROUND AND OBJECTIVE: There are several psychological approaches to treat ED
      with efficacy being revealed by empirical research; however none of them are
      universally accepted. The objective was to compare response to Cognitive
      Behavioral Therapy in patients with different clinical forms of Eating Disorders.
      MATERIAL AND METHOD: Seventy-four patients diagnosed with eating disorders, 32
      with Anorexia nervosa (AN), 19 with Bulimia nervosa (BN) and 23 with Eating
      disorders not otherwise specified (EDNOS) were included. This is a prospective
      and comparative study. Patients were treated by psychotherapy, nutritional
      treatment and pharmacotherapy. RESULTS: The recovery rates in the groups of
      patients with AN, BN and EDNOS were 14 (43.7%), 8 (42.1%), 10 (43.4%),
      respectively, p>0.05. The rates of improvement were 14 (43.7%), 10 (52.6%), 12
      (52.1%) for AN, BN and EDNOS, respectively, p>0.05. Finally, the rate of patients
      who had poor outcome were 3 (9.3%), 1 (5.2%), and 1 (4.3%), p>0.05, for AN, BN,
      and EDNOS, respectively. Cox regression analysis showed that the age of disease
      onset and no use of psychotropic drugs predicted a good response in patients with
      ED. CONCLUSIONS: The treatment response to Cognitive Behavioral Therapy,
      nutritional support and psychotropic drugs in the majority of patients was
      favorable and similar in most patients with different types of Eating Disorders.
      Furthermore, a young age and no use of psychotropic drugs predict a favorable
      outcome in patients with ED.

PMID- 24035413
TI  - [Arthralgias and fractures in an adult male: beyond hypovitaminosis D].

PMID- 24035415
TI  - YAP and TAZ, Hippo signaling targets, act as a rheostat for nuclear SHP2
      function.
AB  - SHP2 is a ubiquitously expressed protein tyrosine phosphatase, deregulation of
      which is associated with malignant neoplasms and developmental disorders. SHP2 is
      required for full activation of RAS-Erk signaling in the cytoplasm and is also
      present in the nucleus, where it promotes Wnt target gene activation through
      dephosphorylation of parafibromin. SHP2 is distributed both to the cytoplasm and
      nucleus at low cell density but is excluded from the nucleus at high cell
      density. Here, we show that SHP2 physically interacts with transcriptional
      coactivators YAP and TAZ, targets of the cell-density-sensing Hippo signal.
      Through the interaction, nonphosphorylated YAP/TAZ promote nuclear
      translocalization of SHP2, which in turn stimulates TCF/LEF- and TEAD-regulated
      genes via parafibromin dephosphorylation. Conversely, YAP/TAZ phosphorylated by
      Hippo signaling sequester SHP2 in the cytoplasm, thereby preventing nuclear
      accumulation of SHP2. Hence, YAP/TAZ serve as a rheostat for nuclear SHP2
      function, which is switched off by the Hippo signal. 

PMID- 24035414
TI  - Adrenocortical zonation results from lineage conversion of differentiated zona
      glomerulosa cells.
AB  - Lineage conversion of differentiated cells in response to hormonal feedback has
      yet to be described. To investigate this, we studied the adrenal cortex, which is
      composed of functionally distinct concentric layers that develop postnatally, the
      outer zona glomerulosa (zG) and the inner zona fasciculata (zF). These layers
      have separate functions, are continuously renewed in response to physiological
      demands, and are regulated by discrete hormonal feedback loops. Their cellular
      origin, lineage relationship, and renewal mechanism, however, remain poorly
      understood. Cell-fate mapping and gene-deletion studies using zG-specific Cre
      expression demonstrate that differentiated zG cells undergo lineage conversion
      into zF cells. In addition, zG maintenance is dependent on the master
      transcriptional regulator Steroidogenic Factor 1 (SF-1), and zG-specific Sf-1
      deletion prevents lineage conversion. These findings demonstrate that
      adrenocortical zonation and regeneration result from lineage conversion and may
      provide a paradigm for homeostatic cellular renewal in other tissues. 

PMID- 24035416
TI  - [Genetic aspects of Alzheimer's disease (Review)].
AB  - Alzheimer's disease is a degenerative brain disorder, which concerns memory,
      cognition and behavior pattern. Its etiology is unknown, it is characterized by
      typical histological lesions: senile plaques and neuro-fibrillary tangles.
      Alzheimer's disease is a multifactorial pathology, characterized by interactions
      between genetic and environmental factors. Genetic factors concern first of all
      the exceptional monogenic forms, characterized by early onset (<60 years),
      autosomal dominant forms. Mutations of the genes coding for amyloid-beta
      precursor protein or preselinins 1 and 2 are involved. The much more frequent
      sporadic forms also have genetic factors, the best studied being the
      apolipoprotein E4 coding allele and some more recent genotypes which will be
      mentioned. No causal, only symptomatic treatments are available.

PMID- 24035417
TI  - Intratumoral gas in hepatocellular carcinoma following transarterial
      chemoembolization: associated factors and clinical impact.
AB  - PURPOSE: To determine the frequency and factors associated with the presence of
      intratumoral gas-containing areas in hepatocellular carcinoma (HCC) on computed
      tomography (CT) scans obtained 4-6 weeks after transarterial chemoembolization.
      MATERIALS AND METHODS: From June 2010 to December 2011, 201 patients underwent
      286 chemoembolization procedures for HCC (n = 497 tumors) and were
      retrospectively included. The presence of intratumoral gas was assessed on CT 4-6
      weeks after chemoembolization. Clinical and biologic data and tumoral and
      chemoembolization procedure characteristics were noted. Factors associated with
      the presence of intratumoral gas were evaluated. Tumor response was assessed by
      using European Society for the Study of the Liver criteria. Tumors containing gas
      or not containing gas were compared by univariate and multivariate analysis.
      RESULTS: Intratumoral gas was found in 26 tumors (5%) after 26 chemoembolization
      procedures (9.1%) in 26 patients (13%). Gas was related to abscess formation in
      three patients (11.5%). On multivariate analysis, a large mean tumor diameter at
      baseline (72.4 mm vs 40.2 mm; P = .003), chemoembolization with drug-eluting
      beads (P = .033), and superselective approach (P = .024) were independently
      associated with the presence of gas. Tumors that exhibited gas-containing areas
      at 1 month had a significantly higher objective response rate than those that did
      not (P < .0001). CONCLUSIONS: Intratumoral gas-containing areas after
      chemoembolization are rarely related to the formation of abscesses. The presence
      of intratumoral gas on CT 4-6 weeks after chemoembolization could be a surrogate
      marker for marked tumor necrosis.

PMID- 24035419
TI  - Changing epidemiologic features of testicular germ cell cancer in Germany:
      corroboration at population level.

PMID- 24035418
TI  - Image guidance for endovascular repair of complex aortic aneurysms: comparison of
      two-dimensional and three-dimensional angiography and image fusion.
AB  - PURPOSE: To evaluate the feasibility of image fusion (IF) of preprocedural
      arterial-phase computed tomography with intraprocedural fluoroscopy for
      roadmapping in endovascular repair of complex aortic aneurysms, and to compare
      this approach versus current roadmapping methods (ie, two-dimensional [2D] and
      three-dimensional [3D] angiography). MATERIALS AND METHODS: Thirty-seven
      consecutive patients with complex aortic aneurysms treated with endovascular
      techniques were retrospectively reviewed; these included aneurysms of digestive
      and/or renal arteries and pararenal and juxtarenal aortic aneurysms. All
      interventions were performed with the same angiographic system. According to the
      availability of different roadmapping software, patients were successively placed
      into three intraprocedural image guidance groups: (i) 2D angiography (n = 9),
      (ii) 3D rotational angiography (n = 14), and (iii) IF (n = 14). X-ray exposure
      (dose-area product [DAP]), injected contrast medium volume, and procedure time
      were recorded. RESULTS: Patient characteristics were similar among groups, with
      no statistically significant differences (P >= .05). There was no statistical
      difference in endograft deployment success between groups (2D angiography, eight
      of nine patients [89%]; 3D angiography and IF, 14 of 14 patients each [100%]).
      The IF group showed significant reduction (P < .0001) in injected contrast medium
      volume versus other groups (2D, 235 mL +/- 145; 3D, 225 mL +/- 119; IF, 65 mL +/-
      28). Mean DAP values showed no significant difference between groups (2D, 1,188
      Gy . cm(2) +/- 1,067; 3D, 984 Gy . cm(2) +/- 581; IF, 655 Gy . cm(2) +/- 457; P =
      .18); nor did procedure times (2D, 233 min +/- 123; 3D, 181 min +/- 53; IF, 189
      min +/- 60; P = .59). CONCLUSIONS: The use of IF-based roadmapping is a feasible
      technique for endovascular complex aneurysm repair associated with significant
      reduction of injected contrast agent volume and similar x-ray exposure and
      procedure time.

PMID- 24035420
TI  - Brain tumors and the area postrema.
AB  - Brain tumors can rarely present with symptoms mistaken for anorexia nervosa. We
      report a patient with a long-standing history of anorexia who developed headaches
      and was found on brain MRI to have a brain tumor in the area of the fourth
      ventricle. On admission, the patient presented with a 4 month history of
      headaches and a 10 year history of "anorexia nervosa". Interestingly, the patient
      did not endorse the classic sense of an altered self-body image. Her body weight
      on admission was 37 kg. The patient underwent surgical resection of the tumor. On
      postoperative day (POD) 1, the patient subjectively reported an increased
      appetite. On POD 2, we documented that she finished her entire food tray for the
      first time during her hospital stay. Her peri-operative course was without any
      complications. She presented for a follow-up clinic visit 2 weeks postoperatively
      and was noted to have a new body weight of 47 kg (10 kg gain). To our knowledge,
      this is the first reported occurrence of a sporadic, and third overall
      occurrence, of a hemangioblastoma that presented with an anorexia nervosa-like
      syndrome that was ultimately cured with surgical resection. In patients
      presenting with a history of psychiatric illness, it is important to consider the
      possibility of underlying, organic pathologies in the central nervous system
      affecting the relevant neuro-anatomical domains.

PMID- 24035421
TI  - Effect of impulse control disorders on disability and quality of life in
      Parkinson's disease patients.
AB  - Impulse control and related disorders (ICRD) are not uncommon in patients with
      idiopathic Parkinson's disease (PD). The present study aimed to investigate the
      effects of ICRD on quality of life (QoL) and disability in PD. From two movement
      disorder clinics in Sydney, Australia, 100 consecutive patients with PD were
      included in the trial. The Unified Parkinson's Disease Rating Scale (UPDRS), Mini
      Mental State Examination and the Parkinson's Disease Questionnaire-39 were used
      to measure disease severity, cognition and disease-specific QoL. The diagnosis of
      ICRD was based on face-to-face structured clinical interviews by three
      psychiatrists with experience in ICRD using the Expanded Structured Clinical
      Interview for the Diagnostic and Statistical Manual IV for Obsessive-Compulsive
      Disorder Related/Spectrum Disorders. ICRD were present in 15% of our patient
      population, and had a negative impact on QoL and Activity of Daily Living (ADL)
      scores. After adjusting for the presence of major depressive disorders and PD
      duration, the effect on emotional wellbeing remained statistically significant
      (p<0.004). Disease duration also correlated with worse QoL and ADL scores. Major
      depression disorders reduced QoL but not ADL. Patients with ICRD tended to suffer
      more from depression than those without ICRD. There were no statistically
      significant differences in age, sex, major depressive disorders, PD duration,
      total levodopa equivalent daily dose, use of dopamine agonists, or UPDRS motor
      score between patients with and without ICDR. 

PMID- 24035422
TI  - Pattern of cerebrospinal immediate early gene c-fos expression in an ovine model
      of non-accidental head injury.
AB  - Expression of the immediate early gene, c-fos, was examined in a large animal
      model of non-accidental head injury ("shaken baby syndrome"). Lambs were used
      because they have a relatively large gyrencephalic brain and weak neck muscles
      resembling a human infant. Neonatal lambs were manually shaken in a manner
      similar to that believed to occur with most abused human infants, but there was
      no head impact. The most striking c-fos expression was in meningothelial cells of
      the cranial cervical spinal cord and, to a lesser degree, in hemispheric,
      cerebellar, and brainstem meninges. Vascular endothelial cells also frequently
      showed c-fos immunopositivity in the meninges and hemispheric white matter. It
      was hypothesised that this c-fos immunoreactivity was due to mechanical stress
      induced by shaking, with differential movement of different craniospinal
      components. 

PMID- 24035423
TI  - Analysis of restenosis after carotid artery stenting: preliminary results using
      computational fluid dynamics based on three-dimensional angiography.
AB  - Currently carotid artery stenting (CAS) is a widely used technique for the
      treatment of carotid artery stenosis. However, some patients with restenosis
      following CAS have been reported, resulting in potential clinical problems. The
      purpose of this study was to investigate the hemodynamic changes before and after
      CAS to find the factors that may influence restenosis. Five patients (two with
      restenosis, three without restenosis) were included in this study. The geometry
      and rheological conditions of the carotid arteries were obtained from three
      dimensional digital subtraction angiography and ultrasound measurements.
      Computational fluid dynamics (CFD) modelling was performed to calculate wall
      shear stress (WSS), wall shear stress gradient (WSSG) and internal carotid artery
      (ICA) flow ratio. In addition, morphologic analysis was carried out. CFD results
      indicated that the WSSG of the restenosis group was significantly larger than
      that of the no-restenosis group. In the restenosis group, the WSS distribution
      after CAS showed a significant variation at the ICA. The average ICA flow ratio
      of the restenosis group was 43.5%, while in the no-restenosis group it was 68.6%.
      Furthermore, there were similar significant differences between the two groups
      during morphology analysis. CFD technology is useful for physicians in estimating
      haemodynamic changes during ICA stenosis treatment. These parameters, including
      ICA flow ratio and WSS distribution, may help to predict carotid restenosis. In
      future, CFD combined with other medical techniques such as digital subtraction
      angiography, MRI and pathology technologies will be available for the clinical
      estimation of ICA restenosis. 

PMID- 24035424
TI  - Plasma brain natriuretic peptide is elevated in the acute phase of intracerebral
      hemorrhage.
AB  - Previous reports have shown that plasma brain natriuretic peptide (BNP) levels
      are increased in patients with subarachnoid hemorrhage and ischemic stroke. We
      examined BNP in patients with intracerebral hemorrhage (ICH). Between June 2006
      and February 2010, we prospectively enrolled consecutive patients with acute ICH
      within 24 hours of onset. The plasma BNP level was measured twice, on admission
      and 4 weeks after onset or at discharge. We investigated whether plasma BNP was
      elevated in the acute phase of ICH and associated factors. The mean +/- standard
      deviation (SD) plasma BNP level of all patients was 71.1 +/- 104.1 pg/mL. The log
      BNP level positively correlated with the cardio-thoracic ratio (r=0.240,
      p=0.0001). Moreover, BNP was significantly associated with intraventricular
      extension (p=0.0039) and hydrocephalus (p=0.0046). The mean +/- SD BNP level of
      patients with cerebellar hemorrhage was the highest (130.2 +/- 152.0 pg/mL),
      followed by brainstem (84.5 +/- 170.6 pg/mL), lobar (72.4 +/- 148.1 pg/mL),
      thalamus (64.8 +/- 72.1 pg/mL), and putamen (59.9 +/- 62.6 pg/mL) hemorrhages. In
      185 patients, BNP was measured in the subacute phase of ICH. The BNP level in the
      acute phase of ICH was significantly higher than that in the subacute phase of
      ICH (69.3 +/- 108.1 versus 21.7 +/- 23.5 pg/mL, p<0.0001). In conclusion, plasma
      BNP appears to be elevated in the acute phase of ICH, particularly in those with
      cerebellar lesions.

PMID- 24035425
TI  - CADASIL presenting with a behavioural variant frontotemporal dementia phenotype.
AB  - The behavioural variant of frontotemporal dementia (bvFTD) is characterised by
      personality change with a decline in cognition. We describe two patients with
      cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukencephalopathy (CADASIL) who presented with behavioural phenotypes similar to
      bvFTD. The first patient presented with progressive personality and behavioural
      change, had florid white matter hyperintensity, and had a novel missense mutation
      C366W in exon 7 of the Notch3 gene. The second patient presented with progressive
      memory impairment and marked personality changes after a transient ischaemic
      attack. In this second patient, the radiological features were subtle and only
      the family history of stroke prompted testing for CADASIL using Notch3
      genotyping. We present these patients to demonstrate that CADASIL may mimic
      bvFTD, with little clinical or radiological evidence to distinguish the two.
      CADASIL may be an under-recognised diagnosis in apparent bvFTD. Screening Notch3
      in a substantial and unselected cohort of frontotemporal dementia patients might
      be appropriate to investigate this possibility. 

PMID- 24035426
TI  - Simulation of CO2-water-rock interactions on geologic CO2 sequestration under
      geological conditions of China.
AB  - The main purpose of this study focused on the feasibility of geologic CO2
      sequestration within the actual geological conditions of the first Carbon Capture
      and Storage (CCS) project in China. This study investigated CO2-water-rock
      interactions under simulated hydrothermal conditions via physicochemical analyses
      and scanning electron microscopy (SEM). Mass loss measurement and SEM showed that
      corrosion of feldspars, silica, and clay minerals increased with increasing
      temperature. Corrosion of sandstone samples in the CO2-containing fluid showed a
      positive correlation with temperature. During reaction at 70 degrees C, 85
      degrees C, and 100 degrees C, gibbsite (an intermediate mineral product) formed
      on the sample surface. This demonstrated mineral capture of CO2 and supported the
      feasibility of geologic CO2 sequestration. Chemical analyses suggested a
      dissolution-reprecipitation mechanism underlying the CO2-water-rock interactions.
      The results of this study suggested that mineral dissolution, new mineral
      precipitation, and carbonic acid formation-dissociation are closely interrelated
      in CO2-water-rock interactions. 

PMID- 24035427
TI  - Detection of verotoxin producing Escherichia coli in marine environments of the
      Caribbean.
AB  - The goal of this study was to determine the potential for Enterohemorrhagic
      Escherichia coli O157:H7 (EHEC) contamination in tropical marine waters. Samples
      were collected from urban, suburban, and rural sites around the islands of Puerto
      Rico and The Republic of Trinidad and Tobago. Quantification of E. coli and EHEC
      was evaluated using MI plates and qPCR. EHEC was detected in six sites in Puerto
      Rico: West of La Parguera Town, Boquilla, Oro Creek, Fishers Association, Joyuda
      Lagoon, and Boqueron Wetland Creek and in two rural sites in Trinidad: Balandra
      Bay and Quinam Bay. Plate count enumeration of E. coli was not a reliable
      indicator for the presence of EHEC. The sites where EHEC was detected on both
      islands are used for recreational bathing, water sports and
      recreational/commercial fisheries and therefore pose a public potential health
      risk. 

PMID- 24035428
TI  - Occurrence and distribution of heavy metals in surface sediments of the Changhua
      River Estuary and adjacent shelf (Hainan Island).
AB  - Heavy metal (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) concentrations in surface
      sediments from the Changhua River Estuary and adjacent shelf, western Hainan
      Island, were conducted to evaluate the level of contamination. Numerical Sediment
      Quality Guidelines (TEL and PEL) were applied to assess adverse biological
      effects of these metals, suggesting that occasional biological effect may occur
      due to As, Cr, Cu, Ni, and Pb. Enrichment factors shown that the significant As
      and Pb contaminations in the study area. Multivariate analysis indicated that the
      sources of Cd, Cr, Cu, Hg, Ni and Zn resulted primarily from natural weathering
      processes, whereas As and Pb were mainly attributed to anthropogenic sources. The
      results of this study would provide a useful aid for sustainable marine
      management in the region. 

PMID- 24035429
TI  - Allocation of marine environmental carrying capacity in the Xiamen Bay.
AB  - Three optimization methods are employed to allocate Marine Environmental Carrying
      Capacity (MECC) in the Xiamen Bay. The hydrodynamic and pollutant fields are
      first simulated by the Princeton Ocean Model. Taking phosphorus as an index of
      the water quality, the response fields are then calculated. These response fields
      represent the relationship between the concentration of the sea zone and the
      pollution sources. Finally, MECC is optimized and distributed in the Xiamen Bay
      by three optimization methods. The results show classical linear optimization can
      only maximize the satisfaction level for one of the stake holders', e.g.,
      dischargers or environmental protection bureau, satisfaction level. However, the
      fuzzy and grey fuzzy optimizations can provide a compromise, and therefore a
      fairer result, by incorporating the conflicting goals of all of the different
      stakeholders. Compared with fuzzy optimization, the grey fuzzy optimization
      provides a more flexible choice for the decision-makers. 

PMID- 24035430
TI  - Could fear of malpractice contribute to ED crowding?

PMID- 24035431
TI  - Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib.
AB  - BRAF V600E is an emerging drug target in lung cancer, but the clinical
      significance of non-V600 BRAF mutations in lung cancer and other malignancies is
      less clear. Here, we report the case of a patient with metastatic lung
      adenocarcinoma with BRAF G469L mutation refractory to vemurafenib. We calculated
      a structure model of this very rare type of mutated BRAF kinase to explain the
      molecular mechanism of drug resistance. This information may help to develop
      effective targeted therapies for cancers with non-V600 BRAF mutations. 

PMID- 24035432
TI  - Life-threatening bacteremia and pyonephrosis caused by Enterococcus hirae.

PMID- 24035433
TI  - Meningococcal factor H-binding protein vaccines with decreased binding to human
      complement factor H have enhanced immunogenicity in human factor H transgenic
      mice.
AB  - Factor H-binding protein (fHbp) is a component of a meningococcal vaccine
      recently licensed in Europe for prevention of serogroup B disease, and a second
      vaccine in clinical development. The protein specifically binds human factor H
      (fH), which down-regulates complement activation and enhances resistance to
      bactericidal activity. There are conflicting data from studies in human fH
      transgenic mice on whether binding of human fH to fHbp vaccines decreases
      immunogenicity, and whether mutant fHbp vaccines with decreased fH binding have
      enhanced immunogenicity. fHbp can be classified into two sub-families based on
      sequence divergence and immunologic cross-reactivity. Previous studies of mutant
      fHbp vaccines with low fH binding were from sub-family B, which account for
      approximately 60% of serogroup B case isolates. In the present study, we
      evaluated the immunogenicity of two mutant sub-family A fHbp vaccines containing
      single substitutions, T221A or D211A, which resulted in 15- or 30-fold lower
      affinity for human fH, respectively, than the corresponding control wild-type
      fHbp vaccine. In transgenic mice with high serum concentrations of human fH, both
      mutant vaccines elicited significantly higher IgG titers and higher serum
      bactericidal antibody responses than the control fHbp vaccine that bound human
      fH. Thus, mutations introduced into a sub-family A fHbp antigen to decrease fH
      binding can increase protective antibody responses in human fH transgenic mice.
      Collectively the data suggest that mutant fHbp antigens with decreased fH binding
      will result in superior vaccines in humans. 

PMID- 24035434
TI  - Cattle immunized against the pathogenic L-alpha-glycerol-3-phosphate oxidase of
      Mycoplasma mycoides subs. mycoides fail to generate neutralizing antibodies and
      succumb to disease on challenge.
AB  - The membrane-associated enzyme L-alpha-glycerol-3-phosphate oxidase (GlpO) of
      Mycoplasma mycoides subs. mycoides (Mmm), the causal agent of contagious bovine
      pleuropneumonia (CBPP) has been identified as a virulence factor responsible for
      the release of toxic by-products such as H2O2 that mediate host cell injury.
      Since CBPP pathogenesis is based on host inflammatory reactions, we have
      determined the capacity of recombinant GlpO to generate in vivo protective
      responses against challenge in immunized cattle. We also investigated whether
      sera raised against recombinant GlpO in cattle and mice inhibit production of
      H2O2 by Mmm. Immunization of cattle with recombinant GlpO did not protect against
      challenge with a virulent strain of Mmm. Further, although both murine and bovine
      antisera raised against recombinant GlpO detected recombinant and native forms of
      GlpO in immunoblot assays with similar titres, only murine antibodies could
      neutralize GlpO enzymatic function. The data raise the possibility that Mmm has
      adapted to evade potential detrimental antibody responses in its definitive host.

PMID- 24035436
TI  - Physical activity in people with COPD, using the National Health and Nutrition
      Evaluation Survey (NHANES) dataset (2003-2006).

PMID- 24035437
TI  - Mechanics of the pulmonary valve in the aortic position.
AB  - Mathematical models can provide valuable information to assess and evaluate the
      mechanical behavior and remodeling of native tissue. A relevant example when
      studying collagen remodeling is the Ross procedure because it involves placing
      the pulmonary autograft in the more demanding aortic valve mechanical
      environment. The objective of this study was therefore to assess and evaluate the
      mechanical differences between the aortic valve and pulmonary valve and the
      remodeling that may occur in the pulmonary valve when placed in the aortic
      position. The results from biaxial tensile tests of pairs of human aortic and
      pulmonary valves were compared and used to determine the parameters of a
      structurally based constitutive model. Finite element analyzes were then
      performed to simulate the mechanical response of both valves to the aortic
      diastolic load. Additionally, remodeling laws were applied to assess the
      remodeling of the pulmonary valve leaflet to the new environment. The pulmonary
      valve showed to be more extensible and less anisotropic than the aortic valve.
      When exposed to aortic pressure, the pulmonary leaflet appeared to remodel by
      increasing its thickness and reorganizing its collagen fibers, rotating them
      toward the circumferential direction. 

PMID- 24035435
TI  - Genetic basis of antigenic variation in foot-and-mouth disease serotype A viruses
      from the Middle East.
AB  - Foot-and-mouth disease viruses (FMDV) from serotype A exhibit high antigenic
      diversity. Within the Middle East, a strain called A-Iran-05 emerged in 2003, and
      subsequently replaced the A-Iran-96 and A-Iran-99 strains that were previously
      circulating in the region. Viruses from this strain did not serologically match
      with the established A/Iran/96 vaccine, although most early samples matched with
      the older A22/Iraq vaccine. However, many viruses from this strain collected
      after 2006 had poor serological match with the A22/Iraq vaccine necessitating the
      development of a new vaccine strain (A/TUR/2006). More recently, viruses from the
      region now exhibit lower cross-reactivity with the A/TUR/2006 antisera
      highlighting the inadequacy of the serotype A vaccines used in the region. In
      order to understand the genetic basis of these antigenic phenotypes, we have
      determined the full capsid sequence for 57 Middle Eastern viruses isolated
      between 1996 and 2011 and analysed these data in context of antigenic
      relationship (r1) values that were generated using antisera to A22/Iraq and
      A/TUR/2006. Comparisons of capsid sequences identified substitutions in
      neutralising antigenic sites (1, 2 and 4), which either individually or together
      underpin these observed antigenic phenotypes. 

PMID- 24035438
TI  - Post-traumatic brachial plexus MRI in practice.
AB  - Injuries are separated into spinal nerve root avulsions (pre-ganglionic lesions)
      and more distal rupture (post-ganglionic lesions). The lesions may be associated
      with different nerve root levels. Spinal MRI is used to diagnose pre-ganglionic
      lesions, which may be present in the absence of pseudomeningoceles. The other
      sequences described are used to diagnose post-ganglionic lesions, regardless of
      the type of lesion. Knowledge that a graftable C5 nerve root is present is
      important in the treatment strategy. Contrast enhancement in the scalene triangle
      does not predict the quality of the nerve root (continuous injury with response
      to peroperative stimulation or division of the root needing grafting).
      Understanding post-traumatic neuronal injuries to the brachial plexus. Knowing
      how to look for spinal MRI abnormalities and post-ganglionic abnormalities. 

PMID- 24035439
TI  - Urinary stones: the contribution of dual energy CT and material decomposition.

PMID- 24035441
TI  - A purified feverfew extract protects from oxidative damage by inducing DNA repair
      in skin cells via a PI3-kinase-dependent Nrf2/ARE pathway.
AB  - BACKGROUND: Environmental factors such as solar ultraviolet (UV) radiation and
      other external aggressors provide an oxidative challenge that is detrimental to
      skin health. The levels of endogenous antioxidants decrease with age, thus
      resulting in less protection and a greater potential for skin damage. The NF-E2
      related factor-2 (Nrf2) - antioxidant response element (ARE) pathway is a primary
      defense mechanism against oxidative stress, and induces the expression of
      antioxidant, detoxification and repair genes. Activation of ARE-Nrf2 can help
      restore oxidative homeostasis of the skin and play a role in inflammatory
      response and DNA repair mechanisms. OBJECTIVE: To evaluate the role of a purified
      parthenolide-depleted Feverfew (PD-Feverfew) extract on the ARE-Nrf2 pathway and
      DNA repair in skin cells. METHODS: These studies were undertaken in primary human
      keratinocytes or KB cells using Luciferase Promoter assay, siRNA transfection
      studies, Western blot analyses, Immunofluorescence microscopy, comet assay and
      quantitative real-time PCR. RESULTS: PD-Feverfew was found to induce Nrf2 nuclear
      translocation and to increase ARE activity in a dose dependent manner.
      Furthermore, knockdown of Nrf2 resulted in suppression of PD-Feverfew-induced ARE
      activity. PD-Feverfew was also found to induce phosphorylation of Akt, a kinase
      downstream of PI3K. Inhibition of PI3K via pre-treatment with the selective
      pharmacological inhibitor, LY294002, abolished PD-Feverfew-induced Nrf2/ARE
      activation. PD-Feverfew also reduced UV-induced DNA damage in a PI3K and Nrf2
      dependent manner. CONCLUSIONS: Therefore, by increasing endogenous defense
      mechanisms and aid in DNA repair of damaged skin cells via activation of a PI3K
      dependent Nrf2/ARE pathway, PD-Feverfew may help protect the skin from numerous
      environmental aggressors.

PMID- 24035440
TI  - Social relationships and healthful dietary behaviour: evidence from over-50s in
      the EPIC cohort, UK.
AB  - Social relationships are an important aspect of a person's social environment
      that can protect against a wide range of chronic conditions and facilitate
      recovery from disease. Social relationships have also been linked to dietary
      behaviour which may be an important pathway through which social circumstances
      exert their influence on health. Yet, questions remain about which structural
      aspects of social relationships most affect healthful dietary behaviours and
      whether different structural components interact to produce a combined effect.
      Using data from adults (>=50 years) in the European Prospective Investigation of
      Cancer-Norfolk study (1996-2002), we examined marital status, living arrangement
      and social isolation in relation to scores for variety of fruit and vegetable
      intake as a marker of diet quality associated with adverse health outcomes. Data
      were analysed with multivariable linear regression models for gender-specific and
      interaction associations. We found that being single or widowed was associated
      with a lower variety score, particularly vegetable variety, and associations were
      enhanced when combined with male gender, living alone or infrequent friend
      contact. Lower variety scores for lone-living were also observed, especially for
      men. Infrequent friend contact interacted with living arrangement to amplify
      negative associations of lone-living with variety, with statistically significant
      differences in contact frequency for vegetable variety. Lower levels of friend
      contact were associated with reduced variety of fruits and vegetables in a graded
      trend for both genders; the trend was more pronounced among men. Family contact
      appeared to have limited association with vegetable variety in men; among women,
      weekly contact was significantly and positively associated with vegetable variety
      compared to daily family contact. Results highlight the importance of considering
      living arrangement and/or frequency of social contact when assessing whether
      widowed, single or lone-living older adults are at risk of lower fruit and
      vegetable variety. 

PMID- 24035442
TI  - Serum granulysin as a possible key marker of the activity of alopecia areata.
AB  - BACKGROUND: Alopecia areata (AA) is an organ-restricted autoimmune condition of
      the hair follicles (HFs) that presents as nonscarring hair loss. A collapse of
      immunoprivilege for cell-mediated cytotoxicity and following attacks by cytotoxic
      T cells to anagen HFs are considered to play a major role in the pathogenesis of
      AA. However, there has been no useful marker for the activity of AA to date.
      OBJECTIVE: The aim of this study is to examine whether granulysin, which is known
      to reflect the activity of cytotoxic immune responses, is related to the disease
      activity of AA. METHODS: We evaluated serum granulysin levels in acute and
      chronic AA patients compared to healthy controls in the perspective of bald skin
      areas, prognosis, and co-existence of other allergic diseases. In addition,
      immunohistochemical analysis for granulysin-, CD4-, CD8-, and CD56-positive cells
      in the lesional skin of acute and chronic AA patients was performed. RESULTS:
      Serum granulysin levels were significantly elevated in both acute and chronic AA
      patients (p=0.00081 and p=0.0012, respectively). Intriguingly, serum granulysin
      levels were significantly associated with the broader bald skin areas (Spearman's
      r=0.59, p=0.017), and poorer prognosis in acute AA patients (p=0.0080). They were
      also associated with co-existence of allergic disorders in AA patients (p=0.026).
      Immunohistochemical staining demonstrated that perifollicular granulysin-bearing
      cells were mainly detected in acute AA lesions with dense lymphocytic
      infiltration, and that these granulysin-bearing cells were consistent with CD8(+)
      T cells. CONCLUSION: The serum granulysin level may be a useful and novel marker
      for the disease activity in the acute phase of AA.

PMID- 24035443
TI  - Increased frequencies of Th17 cells in drug eruptions.

PMID- 24035444
TI  - Biomechanical characteristics of peripheral diabetic neuropathy: A systematic
      review and meta-analysis of findings from the gait cycle, muscle activity and
      dynamic barefoot plantar pressure.
AB  - BACKGROUND: Diabetic peripheral neuropathy is an important cause of foot
      ulceration and limb loss. This systematic review and meta-analysis investigated
      the effect of diabetic peripheral neuropathy on gait, dynamic electromyography
      and dynamic plantar pressures. METHODS: Electronic databases were searched
      systematically for articles reporting the effect of diabetic peripheral
      neuropathy on gait, dynamic electromyography and plantar pressures. Searches were
      restricted to articles published between January 2000 and April 2012. Outcome
      measures assessed included spatiotemporal parameters, lower limb kinematics,
      kinetics, muscle activation and plantar pressure. Meta-analyses were carried out
      on all outcome measures reported by >=3 studies. FINDINGS: Sixteen studies were
      included consisting of 382 neuropathy participants, 216 diabetes controls without
      neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait
      variables. A high level of heterogeneity was noted between studies. Meta-analysis
      results suggested a longer stance time and moderately higher plantar pressures in
      diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot
      compared to controls. Systematic review of studies suggested potential
      differences in the biomechanical characteristics (kinematics, kinetics, EMG) of
      diabetic neuropathy patients. However these findings were inconsistent and
      limited by small sample sizes. INTERPRETATION: Current evidence suggests that
      patients with diabetic peripheral neuropathy have elevated plantar pressures and
      occupy a longer duration of time in the stance-phase during gait. Firm
      conclusions are hampered by the heterogeneity and small sample sizes of available
      studies.

PMID- 24035445
TI  - Early detection of liver steatosis by magnetic resonance imaging in rats infused
      with glucose and intralipid solutions and correlation to insulin levels.
AB  - OBJECTIVE: Magnetic resonance (MR) techniques allow noninvasive fat
      quantification. We aimed to investigate the accuracy of MR imaging (MRI), MR
      spectroscopy (MRS) and histological techniques to detect early-onset liver
      steatosis in three rat phenotypes assigned to an experimental glucolipotoxic
      model or a control group. MATERIALS AND METHODS: This study was approved by the
      institutional committee for the protection of animals. Thirty-two rats (13 young
      Wistar, 6 old Wistar and 13 diabetic Goto-Kakizaki rats) fed a standard diet were
      assigned to a 72h intravenous infusion of glucose and Intralipid fat emulsion or
      a saline infusion. Plasma insulin levels were measured. Steatosis was quantified
      in ex vivo livers with gradient-recalled multi-echo MRI, MRS and histology as fat
      fractions (FF). RESULTS: A significant correlation was found between multi-echo
      MRI-FF and MRS-FF (r=0.81, p<0.01) and a weaker correlation was found between
      histology and MRS-FF (r=0.60, p<0.01). MRS and MRI accurately distinguished young
      Wistar and Goto-Kakizaki rats receiving the glucose+Intralipid infusion from
      those receiving the saline control whereas histology did not. Significant
      correlations were found between MRI or MRS and insulin plasma level (r=0.63,
      p<0.01; r=0.57, p<0.01), and between MRI or MRS and C-peptide concentration
      (r=0.54, p<0.01; r=0.44, p<0.02). CONCLUSIONS: Multi-echo MRI and MRS may be more
      sensitive to measure early-onset liver steatosis than histology in an
      experimental glucolipotoxic rat model.

PMID- 24035447
TI  - Safety and effectiveness of LAP-BAND AP System: results of Helping Evaluate
      Reduction in Obesity (HERO) prospective registry study at 1 year.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding has several distinctive
      features, including band adjustability, easy reversibility, and lack of
      malabsorption, which contribute to its widespread use. The LAP-BAND AP System
      (LBAP; Allergan, Inc.), a redesigned and improved version of the original device,
      was approved by the US Food and Drug Administration in 2006. Because of limited
      information on LBAP, this study prospectively assesses the efficacy and safety of
      LBAP in real-world settings at clinical centers located in North America, Europe,
      and Australia. STUDY DESIGN: This interim report of the ongoing 5-year
      prospective, observational, international, multicenter registry, Helping Evaluate
      Reduction in Obesity (HERO) Study (NCT00953173), describes clinical efficacy and
      safety of LBAP in real-world settings at 1 year. RESULTS: One thousand one
      hundred and six patients were implanted with LBAP and 1-year data were available
      from 834 patients for efficacy analysis. At 1 year, the mean (SD) percentage of
      excess weight loss was 39.8% (22.3%), of weight loss was 16.9% (9.0%), and the
      mean (SD) body mass index decreased to 37.7 (7.0) kg/m(2) from 45.1 (6.9) kg/m(2)
      at baseline. Patients with type 2 diabetes mellitus or hypertension showed
      significant improvements at 1 year post LBAP (both p < 0.005). The most common
      device-related complications were port displacement (n = 20 [1.8%]), pouch
      dilation (n = 12 [1.1%]), band slippage (n = 7 [0.6%]), and band erosion (n = 5
      [0.5%]). Eighteen (1.6%) patients had the device explanted. CONCLUSIONS: At 1
      year post LBAP, progressive weight loss was associated with improvement and/or
      resolution of comorbid conditions and was safe and well tolerated. Patient follow
      up continues.

PMID- 24035446
TI  - Molecular mechanisms of incretin hormone secretion.
AB  - Incretin peptides (glucagon-like peptide-1 (GLP-1) and glucose-dependent
      insulinotropic polypeptide (GIP)) are secreted from enteroendocrine cells in the
      intestinal epithelium, and help to coordinate metabolic responses to food
      ingestion. A number of molecular mechanisms have recently been defined that
      underlie carbohydrate, lipid and protein sensing in gut endocrine cells. Knockout
      mice lacking sodium glucose tranporter-1 (SGLT-1) or the short chain fatty acid
      sensing receptor FFAR2 (GPR43), for example, have highlighted the importance of
      these molecules in incretin secretion. This review outlines our current
      understanding of sensory pathways in incretin secreting cells and highlights the
      therapeutic potential of targeting them for the development of novel therapies
      for obesity and diabetes. 

PMID- 24035448
TI  - Surgical complications impact patient perception of hospital care.
AB  - BACKGROUND: Public reporting of the Hospital Consumer Assessment of Healthcare
      Providers and Systems survey is designed to produce data on patients' perceptions
      of the quality of hospital care. The aim of this study was to assess the impact
      of complications on patient responses to Hospital Consumer Assessment of
      Healthcare Providers and Systems "top-box" (most favorable) scores. STUDY DESIGN:
      All patients who underwent a colorectal procedure from October 2009 to June 2012
      at a single center were included. Patient complications were categorized as
      major, minor, or no complications and "surgical technique" or "medical." Chi
      square and Wilcoxon rank sum tests were used to compare binary and ordinal top
      box scores, respectively. RESULTS: One thousand four hundred and nine surveys
      were collected for 1,233 patients (mean age 53 +/- 15.7 years; 701 [52.2%]
      females) who underwent 955 (67.8%) major abdominal, 114 (8.1%) anorectal, and 340
      (24.1%) stoma-related operations. There were 195 (13.8%) major and 396 (28.1%)
      minor complications. There were 159 (11.3%) technique complications and 411
      (29.2%) medical complications. Patients without any complications were more
      likely to recommend the hospital than those with complications (p = 0.023)
      irrespective of type of complication (minor vs major; p = 0.72 or technique vs
      medical; p = 0.5). Responsiveness of hospital staff was also reported as higher
      for patients without complications (p = 0.0003) and the type of complication did
      not influence this assessment (minor vs major; p = 0.71 and technique vs medical;
      p = 0.95). CONCLUSIONS: The occurrence of any complication after colorectal
      surgery adversely impacts patients' self-reported perceptions of hospital care as
      measured by Hospital Consumer Assessment of Healthcare Providers and Systems. An
      instrument that more accurately reflects patients' assessment of quality in the
      context of variations in patient, disease, and surgical factors is required.

PMID- 24035449
TI  - Placing a saline bag underneath the heart enhances transgastric transesophageal
      echocardiographic imaging during cardiac displacement for off-pump coronary
      artery bypass surgery.
AB  - OBJECTIVE: The authors hypothesized that placing a saline bag (saline-filled
      surgical glove) underneath a displaced heart would improve ultrasound
      transmission for transgastric (TG) imaging and transesophageal echocardiography
      (TEE) to visualize left ventricular regional wall motion (LV-RWM) during cardiac
      displacement for off-pump coronary artery bypass (OPCAB) surgery. DESIGN:
      Prospective observational study. SETTING: Tertiary University Hospital.
      PARTICIPANTS: Adult patients undergoing OPCAB surgery. INTERVENTIONS:
      Intraoperative TEE examination MEASUREMENT AND MAIN RESULTS: For off-line
      analyses of LV-readable segments, mid-esophageal (ME, 4-chamber, 2-chamber, and
      long-axis) and TG (basal- and mid-short-axis) TEE views were recorded under 3
      different intraoperative conditions in 13 cases of OPCAB surgery: Before cardiac
      displacement (Tcontrol), after cardiac displacement (Tdisplaced), and after
      placing the saline bag underneath the displaced heart (Tsaline-bag). There were
      more LV-readable segments in the 17-segment model using integrated ME and TG
      views(ME + TG views) at Tsaline-bag and Tcontrol (mean[95% confidence interval],
      17[17-17] and 17[17-17]) than using ME+TG at Tdisplaced (15[15-16], P = 0.002 and
      P<0.001, respectively). Using ME + TG views provided more LV-readable segments in
      the 17-segment model than using ME views at Tsaline-bag (vs. 16[14-16], P <
      0.001), but not at Tdisplaced (vs. 15[14-15]). Incidences of inadequate RWM
      monitoring (LV-readable segments<14/17 using ME + TG views) at Tsaline-bag and
      Tcontrol (all 0/13) were less frequent than at Tdisplaced (3/13, all P = 0.038).
      There were more LV-readable segments in TG basal- and mid-short-axis views at
      Tsaline-bag (median [range], 6[5-6] and 5[5-6]) than at Tdisplaced (0[0-2] and
      0[0-1], all P < 0.05). CONCLUSIONS: Placing a saline bag underneath the displaced
      heart enhances the ability of TEE to visualize global LV-RWM by improving TG TEE
      imaging during OPCAB surgery.

PMID- 24035450
TI  - A heart with six chambers: a remarkable anomaly or a late complication after
      cardiac surgery?

PMID- 24035452
TI  - Not only osmoprotectant: betaine increased lactate dehydrogenase activity and L
      lactate production in lactobacilli.
AB  - Lactobacilli are commonly used for industrial production of polymer-grade L
      lactic acid. The present study tested the Tween 80 alternative betaine in L
      lactate production by several industrial lactobacilli. In flask fermentation of
      Lactobacillus casei, Lactobacillus buchneri, Lactobacillus lactis and
      Lactobacillus rhamnosus, the betaine addition (2g/l) had similar osmoprotectant
      effect with Tween 80 but had increased the lactate dehydrogenase activities and L
      lactate production than Tween 80 control. In fed-batch fermentation of L. casei,
      betaine supplementation improved the L-lactic acid titer to 190 g/l, the yield to
      95.5% (g L-lactic acid/g glucose), the productivity to 2.6g/lh, and the optical
      purity to 97.0%. The results demonstrated that supplementation of Tween 80
      alternative - betaine in the fermentation medium is feasible for industrial l
      lactic acid fermentation by lactobacilli, which will improve the lactate
      production but will not increase the process costs and modify any process
      conditions.

PMID- 24035451
TI  - Tudor: a versatile family of histone methylation 'readers'.
AB  - The Tudor domain comprises a family of motifs that mediate protein-protein
      interactions required for various DNA-templated biological processes. Emerging
      evidence demonstrates a versatility of the Tudor family domains by identifying
      their specific interactions to a wide variety of histone methylation marks. Here,
      we discuss novel functions of a number of Tudor-containing proteins [including
      Jumonji domain-containing 2A (JMJD2A), p53-binding protein 1 (53BP1), SAGA
      associated factor 29 (SGF29), Spindlin1, ubiquitin-like with PHD and RING finger
      domains 1 (UHRF1), PHD finger protein 1 (PHF1), PHD finger protein 19 (PHF19),
      and SAWADEE homeodomain homolog 1 (SHH1)] in 'reading' unique methylation events
      on histones in order to facilitate DNA damage repair or regulate transcription.
      This review covers our recent understanding of the molecular bases for histone
      Tudor interactions and their biological outcomes. As deregulation of Tudor
      containing proteins is associated with certain human disorders, pharmacological
      targeting of Tudor interactions could provide new avenues for therapeutic
      intervention. 

PMID- 24035453
TI  - An integrin-linked machinery of cytoskeletal regulation that enables experimental
      tumor initiation and metastatic colonization.
AB  - Recently extravasated metastatic cancer cells use the Rif/mDia2 actin
      nucleating/polymerizing machinery in order to extend integrin beta1-containing,
      filopodium-like protrusions (FLPs), which enable them to interact productively
      with the surrounding extracellular matrix; this process governs the initial
      proliferation of these cancer cells. Here, we identify the signaling pathway
      governing FLP lifetime, which involves integrin-linked kinase (ILK) and beta
      parvin, two integrin:actin-bridging proteins that block cofilin-mediated actin
      filament severing. Notably, the combined actions of Rif/mDia2 and ILK/beta
      parvin/cofilin pathways on FLPs are required not only for metastatic outgrowth
      but also for primary tumor formation following experimental implantation. This
      provides one mechanistic explanation for how the epithelial-mesenchymal
      transition (EMT) program imparts tumor-initiating powers to carcinoma cells,
      since it enhances FLP formation through the activation of ILK/beta-parvin/cofilin
      pathway. 

PMID- 24035454
TI  - The high-fat high-fructose hamster as an animal model for niacin's biological
      activities in humans.
AB  - OBJECTIVE: Niacin has been used for more than 50 years to treat dyslipidemia, yet
      the mechanisms underlying its lipid-modifying effects remain unknown, a situation
      stemming at least in part from a lack of validated animal models. The objective
      of this study was to determine if the dyslipidemic hamster could serve as such a
      model. MATERIALS/METHODS: Dyslipidemia was induced in Golden Syrian hamsters by
      feeding them a high-fat, high-cholesterol, and high-fructose (HF/HF) diet. The
      effect of high-dose niacin treatment for 18 days and 28 days on plasma lipid
      levels and gene expression was measured. RESULTS: Niacin treatment produced
      significant decreases in plasma total cholesterol (TC), low-density lipoprotein
      cholesterol (LDL-C), triglycerides (TG), and free fatty acids (FFA), but had no
      measureable effect on high-density lipoprotein cholesterol (HDL-C) in the
      dyslipidemic hamster. Niacin treatment also produced significant increases in
      hepatic adenosine ATP-Binding Cassette A1 (ABCA1) mRNA, ABCA1 protein,
      apolipoprotein A-I (Apo A-I) mRNA, and adipose adiponectin mRNA in these animals.
      CONCLUSIONS: With the exception of HDL-C, the lipid effects of niacin treatment
      in the dyslipidemic hamster closely parallel those observed in humans. Moreover,
      the effects of niacin treatment on gene expression of hepatic proteins related to
      HDL metabolism are similar to those observed in human cells in culture. The HF/HF
      fed hamster could therefore serve as an animal model for niacin's lowering of
      proatherogenic lipids and mechanisms of action relative to lipid metabolism.

PMID- 24035456
TI  - The relationships between tracheal index and lung volume parameters in mild-to
      moderate COPD.
AB  - BACKGROUND: Although elongated morphological changes in the trachea are known to
      be related to lung function in chronic obstructive pulmonary disease (COPD),
      whether the tracheal morphological changes are associated with airflow
      limitations or overinflation of the lung in the early stages of COPD has not yet
      been determined. Thus, our aim was to investigate the association of tracheal
      index (TI) with lung function parameters, including lung volume parameters, in
      COPD patients with mild-to-moderate airflow limitations. MATERIALS AND METHODS: A
      retrospective study was conducted in 193 COPD patients with GOLD grades 1-2 (post
      bronchodilator forced expiratory volume in 1s [FEV1] >= 50% predicted with
      FEV1/forced vital capacity ratio <= 70%; age range, 40-81) and 193 age- and
      gender-matched subjects with normal lung function as a control group (age range,
      40-82). Two independent observers measured TI at three anatomical levels on chest
      radiographs and CT scans. RESULTS: Compared with the control group, TI was
      reduced significantly and "saber-sheath trachea" was observed more frequently in
      COPD patients. Patients with GOLD grade 2 disease had a lower TI than those with
      GOLD grade 1. TI had apparent inverse correlations with total lung capacity,
      functional residual capacity, and residual volume, regardless of the anatomical
      level of the trachea. Even after adjustments for covariates, this association
      persisted. CONCLUSIONS: TI is reduced even in mild-to-moderate COPD patients, and
      TI measured on chest CT shows significant inverse relationships with all lung
      volume parameters assessed, suggesting that tracheal morphology may change during
      the early stages of COPD.

PMID- 24035455
TI  - Acceleration of tendon healing using US guided intratendinous injection of
      bevacizumab: first pre-clinical study on a murine model.
AB  - PURPOSE: Tendinopathy shows early disorganized collagen fibers with neo
      angiogenesis on histology. Peri-tendinous injection of corticosteroid is the
      commonly accepted strategy despite the abscence of inflammation in tendinosis.
      The aim of our study was to assess the potential of intratendinous injection of
      an anti-angiogenic drug (bevacizumab, AA) to treat tendinopathy in a murine model
      of patellar and Achilles tendinopathy, and to evaluate its local toxicity.
      MATERIALS AND METHOD: Forty rats (160 patellar and Achilles tendons) were used
      for this study. We induced tendinosis (T+) in 80 tendons by injecting under
      ultrasonography (US) guidance Collagenase 1((r)) (day 0 = D0, patellar = 40 and
      Achilles = 40). Clinical examination and tendon US were performed at D3,
      immediately followed by either AA (AAT+, n = 40) or physiological serum (PST+, n
      = 40, control) US-guided intratendinous injection. Follow-up at D6 and D13 using
      clinical, US and histology, and comparison between the 2 groups were performed.
      To study AA toxicity we compared the 80 remaining normal tendons (T-) after
      injecting AA in 40 (AAT-). RESULTS: All AAT+ showed a better joint mobilization
      compared to PST+ at D6 (p = 0.004) with thinner US tendon diameters (p<0.004),
      and less disorganized collagen fibers and neovessels on histology (p<0.05). There
      was no difference at D13 regarding clinical status, US tendon diameter and
      histology (p>0.05). Comparison between AAT- and T- showed no AA toxicity on
      tendon (p = 0.18). CONCLUSION: Our study suggests that high dose mono-injection
      of AA in tendinosis, early after the beginning of the disease, accelerates
      tendon's healing, with no local toxicity.

PMID- 24035457
TI  - Microplastic pollution in deep-sea sediments.
AB  - Microplastics are small plastic particles (<1 mm) originating from the
      degradation of larger plastic debris. These microplastics have been accumulating
      in the marine environment for decades and have been detected throughout the water
      column and in sublittoral and beach sediments worldwide. However, up to now, it
      has never been established whether microplastic presence in sediments is limited
      to accumulation hot spots such as the continental shelf, or whether they are also
      present in deep-sea sediments. Here we show, for the first time ever, that
      microplastics have indeed reached the most remote of marine environments: the
      deep sea. We found plastic particles sized in the micrometre range in deep-sea
      sediments collected at four locations representing different deep-sea habitats
      ranging in depth from 1100 to 5000 m. Our results demonstrate that microplastic
      pollution has spread throughout the world's seas and oceans, into the remote and
      largely unknown deep sea.

PMID- 24035458
TI  - Pyrethroid effects on freshwater invertebrates: a meta-analysis of pulse
      exposures.
AB  - Pyrethroids are widely used insecticides that may seriously harm aquatic
      organisms. Being strongly hydrophobic, pyrethroids in solution occur only in
      short pulses but may be retained in sediments for longer periods. Consequently,
      most studies consider the chronic exposure of sediment dwelling organisms. We
      collected data from 16 studies to determine effect thresholds for stream
      macroinvertebrates exposed to short pyrethroid pulses evaluating lethal and
      sublethal ecologically relevant endpoints. Dose-response models showed EC50 for
      lethality, functional and behavioural endpoints down to 1/100, 1/100 and 1/1000
      of the 48 h LC50 for Daphnia magna, respectively. The results indicate that the
      overall sensitivity of stream macroinvertebrates to pyrethroids may be higher
      than previously believed. This review shows the relevance of incorporating data
      on sublethal endpoints and appropriate post-exposure observation periods in
      future studies. The current risk assessment procedures and the higher tier
      approach are discussed in the light of our results.

PMID- 24035459
TI  - Comparing nutrition environments in bodegas and fast-food restaurants.
AB  - Many small grocery stores or "bodegas" sell prepared or ready-to-eat items,
      filling a niche in the food environment similar to fast-food restaurants.
      However, little comparative information is available about the nutrition
      environments of bodegas and fast-food outlets. This study compared the nutrition
      environments of bodegas and national chain fast-food restaurants using a common
      audit instrument, the Nutrition Environment Measures Study in Restaurants (NEMS
      R) protocol. The analytic sample included 109 bodegas and 107 fast-food
      restaurants located in New York City neighborhoods in the upper third and lower
      third of the census tract poverty rate distribution. Inter-rater reliability was
      evaluated in 102 food outlets, including 31 from the analytic sample and 71 from
      a supplementary convenience sample. The analysis compared scores on individual
      NEMS-R items, a total summary score, and subscores indicating healthy food
      availability, nutrition information, promotions of healthy or unhealthy eating,
      and price incentives for healthy eating, using t tests and chi(2) statistics to
      evaluate differences by outlet type and neighborhood poverty. Fast-food
      restaurants were more likely to provide nutrition information, and bodegas scored
      higher on healthy food availability, promotions, and pricing. Bodegas and fast
      food restaurants had similar NEMS-R total scores (bodegas 13.09, fast food 14.31;
      P=0.22). NEMS-R total scores were higher (indicating healthier environments) in
      low- than high-poverty neighborhoods among both bodegas (14.79 vs 11.54; P=0.01)
      and fast-food restaurants (16.27 vs 11.60; P<0.01). Results imply different
      policy measures to improve nutrition environments in the two types of food
      outlets. 

PMID- 24035460
TI  - Diet quality is inversely associated with C-reactive protein levels in urban, low
      income African-American and white adults.
AB  - BACKGROUND: C-reactive protein (CRP), an inflammatory biomarker, is influenced by
      many factors, including socioeconomic position, genetics, and diet. The inverse
      association between diet and CRP is biologically feasible because micronutrients
      with antioxidative properties may enable the body to manage the balance between
      production and accumulation of reactive species that cause oxidative stress.
      OBJECTIVE: To determine the quality of the diet consumed by urban, low-income
      African-American and white adults aged 30 to 64 years, and association of diet
      quality with CRP. DESIGN: Data from a cross-sectional study were used to evaluate
      diet quality assessed by mean adequacy ratio (MAR). Two 24-hour recalls were
      collected by trained interviewers using the US Department of Agriculture
      automated multiple pass method. PARTICIPANTS: The sample consisted of Healthy
      Aging in Neighborhoods of Diversity across the Life Span baseline study
      participants, 2004-2009, who completed both recalls (n=2,017). MAIN OUTCOME
      MEASURES: MAR equaled the average of the ratio of intakes to Recommended Dietary
      Allowance for 15 vitamins and minerals. CRP levels were assessed by the
      nephelometric method utilizing latex particles coated with CRP monoclonal
      antibodies. STATISTICAL ANALYSIS: Linear ordinary least square regression and
      generalized linear models were performed to determine the association of MAR
      (independent variable) with CRP (dependent variable) while adjusting for
      potential confounders. RESULTS: MAR scores ranged from 74.3 to 82.2. Intakes of
      magnesium and vitamins A, C, and E were the most inadequate compared with
      Estimated Average Requirements. CRP levels were significantly associated with
      MAR, dual-energy x-ray absorptiometry-measured body fat, and hypertension. A 10%
      increase in MAR was associated with a 4% decrease in CRP. CONCLUSIONS: The MAR
      was independently and significantly inversely associated with CRP, suggesting
      diet is associated with the regulation of inflammation. Interventions to assist
      people make better food choices may not only improve diet quality but also their
      health, thereby possibly reducing risk for cardiovascular disease.

PMID- 24035461
TI  - Sensory-based nutrition pilot intervention for women.
AB  - Negative effects of restrained eating (ie, concerns about dieting and weight
      control) have been observed in eating behaviors. Such findings underscore the
      need to develop more positive approaches to promote healthy eating behaviors. The
      objectives of this pilot randomized controlled trial were to investigate and
      determine whether sensory-based intervention influenced eating-related attitudes
      and behaviors among restrained women, as well as reliance on physical signals for
      hunger and satiety. Between January and September 2011, data were collected using
      validated questionnaires (Restraint Scale, Three-Factor Eating Questionnaire,
      Mindful Eating Questionnaire, and Intuitive Eating Scale) at baseline (T=1), the
      end of the intervention period (T=2), and 12 weeks post intervention (T=3). At
      T=1, women (n=50) from Quebec City, Canada, were randomly assigned to an
      intervention group (sensory-based intervention) or a waiting list control group.
      Statistical analyses were conducted using mixed models, including the group,
      time, and group-by-time interaction. Women from the intervention group showed a
      significant decrease in Three-Factor Eating Questionnaire-Disinhibition and a
      significant increase in Mindful Eating Questionnaire-Disinhibition at T=2 vs T=3
      (P=0.02 and P=0.02, respectively) and at T=3 vs T=1 (P=0.003 and P=0.002,
      respectively). Women from the intervention group also showed a significant
      increase in Intuitive Eating Scale-Unconditional Permission to Eat at T=2 vs T=1
      (P<0.0001) and at T=3 vs T=1 (P<0.0001). These preliminary data suggest that
      sensory-based intervention can be a promising approach to improve eating-related
      attitudes and behaviors among restrained women, without exacerbating other
      behaviors such as restrained eating. 

PMID- 24035462
TI  - Combined effects of cadmium and zinc on growth, tolerance, and metal accumulation
      in Chara australis and enhanced phytoextraction using EDTA.
AB  - Chara australis (R. Br.) is a macrophytic alga that can grow in and accumulate Cd
      from artificially contaminated sediments. We investigated the effects of Zn
      independently and in combination with Cd on C. australis growth, metal tolerance,
      and uptake. Plant growth was reduced at concentrations >= 75 mg Zn (kg soil)-1.
      Zn also increased the concentration of glutathione in the plant, suggesting
      alleviation of stress. Phytotoxic effects were observed at >= 250 mg added Zn (kg
      soil)-1. At 1.5mg Zn (kg soil)-1, the rhizoid bioconcentration factor (BCF) was
      >1.0 for both Cd and Zn. This is a criterion for hyperaccumulator status, a
      commonly used benchmark for utility in remediation of contaminated soils by
      phytoextraction. There was no significant interaction between Cd and Zn on
      accumulation, indicating that Chara should be effective at phytoextraction of
      mixed heavy metal contamination in sediments. The effects of the chelator,
      ethylenediaminetetraacetic acid (EDTA), were also tested. Moderate levels of EDTA
      increased Cd and Zn accumulation in rhizoids and Cd BCF of shoots, enhancing
      Chara's potential in phytoremediation. This study demonstrates for the first time
      the potential of macroalgae to remove metals from sediments in aquatic systems
      that are contaminated with a mixture of metals.

PMID- 24035463
TI  - Physician communication styles in initial consultations for hematological cancer.
AB  - OBJECTIVE: To characterize practices in subspecialist physicians' communication
      styles, and their potential effects on shared decision-making, in second-opinion
      consultations. METHODS: Theme-oriented discourse analysis of 20 second-opinion
      consultations with subspecialist hematologist-oncologists. RESULTS: Physicians
      frequently "broadcasted" information about the disease, treatment options,
      relevant research, and prognostic information in extended, often-uninterrupted
      monologs. Their communicative styles had one of two implications: conveying
      options without offering specific recommendations, or recommending one without
      incorporating patients' goals and values into the decision. Some physicians,
      however, used techniques that encouraged patient participation. CONCLUSIONS:
      Broadcasting may be a suboptimal method of conveying complex treatment
      information in order to support shared decision-making. Interventions could teach
      techniques that encourage patient participation. PRACTICE IMPLICATIONS:
      Techniques such as open-ended questions, affirmations of patients' expressions,
      and pauses to check for patient understanding can mitigate the effects of
      broadcasting and could be used to promote shared decision-making in information
      dense subspecialist consultations.

PMID- 24035464
TI  - First reported case of pneumonia caused by Cedecea lapagei in America.
AB  - Cedecea represents a genus in the Enterobacteriaceae family that has been rarely
      associated with human infection. The clinical relevance of Cedecea lapagei has
      yet to be elucidated. This is the first reported case of pneumonia due to C.
      lapagei in a patient with acute promyelocytic leukemia. 

PMID- 24035465
TI  - More than tree dimensions: inter-lineage evolution's ecological importance.
AB  - Horizontal transfer of genes has sometimes been viewed as a nuisance for the work
      of understanding the evolutionary history of lineages. Recent work has shown that
      clever analysis of inter-lineage gene transfer is productive and has tremendous
      explanatory power, in particular, for niche adaptation. These studies alter our
      perception of what are the fundamental units of evolution and selection. 

PMID- 24035466
TI  - Altered vascular activation due to deficiency of the NADPH oxidase component
      p22phox.
AB  - BACKGROUND: Reactive oxygen species generated by nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase play important roles in vascular
      activation. The p22(phox) subunit is necessary for the activity of NADPH oxidase
      complexes utilizing Nox1, Nox2, Nox3, and Nox4 catalytic subunits. METHODS: We
      assessed p22(phox)-deficient mice and human tissue for altered vascular
      activation. RESULTS: Mice deficient in p22(phox) were smaller than their wild
      type littermates but showed no alteration in basal blood pressure. The wild-type
      littermates were relatively resistant to forming intimal hyperplasia following
      carotid ligation, and the intimal hyperplasia that developed was not altered by
      p22(phox) deficiency. However, at the site of carotid artery ligation, the
      p22(phox)-deficient mice showed significantly less vascular elastic fiber loss
      compared with their wild-type littermates. This preservation of elastic fibers
      was associated with a reduced matrix metallopeptidase (MMP) 12/tissue inhibitor
      of metalloproteinase (TIMP) 1 expression ratio. A similar decrease in the
      relative MMP12/TIMP1 expression ratio occurred in human coronary artery smooth
      muscle cells upon knockdown of the hydrogen peroxide responsive kinase
      CK1alphaLS. In the ligated carotid arteries, the p22(phox)-deficient mice showed
      reduced expression of heterogeneous nuclear ribonucleoprotein C (hnRNP-C),
      suggesting reduced activity of CK1alphaLS. In a lung biopsy from a human patient
      with p22(phox) deficiency, there was also reduced vascular hnRNP-C expression.
      CONCLUSIONS: These findings indicate that NADPH oxidase complexes modulate
      aspects of vascular activation including vascular elastic fiber loss, the
      MMP12/TIMP1 expression ratio, and the expression of hnRNP-C. Furthermore, these
      findings suggest that the effects of NADPH oxidase on vascular activation are
      mediated in part by protein kinase CK1alphaLS.

PMID- 24035467
TI  - Equine endometrial cytology and bacteriology: effectiveness for predicting live
      foaling rates.
AB  - Endometritis is an important cause of sub-fertility in mares. The critical
      indicator of reproductive success and financial return for commercial studs is
      live foaling rate. Endometrial bacteriology and/or cytology are used to diagnose
      endometritis and thus identify mares at risk of early embryonic death. However,
      mares with endometritis may conceive but then abort in late gestation. The aims
      of this study were to establish, as part of a standard breeding examination (1)
      whether a threshold percentage of uterine polymorphonuclear neutrophils (PMNs)
      exists above which a significant reduction in live foaling rate is evident; (2)
      the relationship of a positive bacteriology result to live foaling rate, and (3)
      the relationship of a combination of positive cytology and bacteriology result to
      live foaling rate. Guarded endometrial swabs (n=2660) were collected from 1621
      Thoroughbred mares on 17 commercial stud farms by five veterinarians during a
      single breeding season. All mares were included regardless of age, history or
      parity. Cytological and bacteriological analyses were performed on each swab and
      subsequent live foaling rates recoded. Data were analysed by comparing 0%, >= 1%,
      >= 2%, >= 5% or >= 25% PMNs of total cells counted, or categories of bacterial
      growth to live foaling rates, using Pearson's chi-squared test. A threshold value
      of >= 1% PMNs, culture of a single bacterial isolate and a combination of both
      these parameters were associated with significantly reduced live foaling rates.
      Positive cytology alone, positive bacterial culture alone, or combined positive
      cytology and bacteriology were equally indicative of the likelihood of a mare
      producing a live foal.

PMID- 24035468
TI  - The proteasome inhibitor bortezomib inhibits the growth of canine malignant
      melanoma cells in vitro and in vivo.
AB  - Canine malignant melanomas are highly aggressive and fatal neoplasms. In the
      present report, 21 drugs that target specific signalling pathways were screened
      for their growth inhibitory activity on three canine malignant melanoma cell
      lines. The proteasome inhibitor bortezomib inhibited the growth of these cell
      lines. The growth inhibitory properties of bortezomib were then examined using
      nine canine malignant melanoma cell lines. Bortezomib demonstrated potent growth
      inhibitory activity in all cell lines with calculated IC50 values of 3.5-5.6 nM.
      Because suppression of the NF-kappaB pathway by preventing proteasomic
      degradation of I kappaB is an important mechanism of the anti-tumour activity of
      bortezomib, the activation status of and the effect of bortezomib on the NF
      kappaB pathway were examined using a canine malignant melanoma cell line, CMM-1.
      The NF-kappaB pathway was constitutively activated in CMM-1 cells and bortezomib
      efficiently suppressed this activated pathway. Using a CMM-1 xenograft mouse
      model, bortezomib also significantly inhibited tumour growth via suppression of
      tumour cell proliferation. Collectively, these findings suggest that bortezomib
      has growth inhibitory activity against canine malignant melanomas potentially
      through suppression of the constitutively activated NF-kappaB pathway. Targeted
      therapy using bortezomib could therefore be beneficial in the management of
      canine malignant melanomas.

PMID- 24035470
TI  - Influence of modifiable risk factors on the incidence of stillbirth/perinatal
      mortality in dairy cattle.
AB  - Bovine perinatal mortality is defined as the death of a full-term calf before,
      during or up to 48 h after calving. Recent studies indicate that the prevalence
      of bovine perinatal mortality is increasing, particularly in Holstein primiparae.
      Factors leading to a greater incidence of dystocia are the most important
      modifiable variables influencing the risk of perinatal mortality. Modifiable
      predictors are largely (age at first calving, breeding method, sire, calving
      management, feto-maternal health status and gestational nutrition) or moderately
      (calf breed, sex, gestation length) under the control of the dairy farm manager.
      Unlike non-modifiable risk factors, such as primiparity and fetal plurality,
      these factors can be manipulated to reduce the incidence of perinatal mortality.

PMID- 24035469
TI  - Characterization of the inflammatory response to anthelmintic treatment of ponies
      with cyathostominosis.
AB  - Cyathostomins can cause a severe inflammation of equine large intestine
      characterized by substantial ventral edema and pronounced protein loss.
      Anthelmintic treatment of horses can result in a localized inflammatory response
      in the colonic mucosa of clinically normal horses. The aim of this study was to
      evaluate the systemic inflammatory response of ponies naturally infected with
      cyathostomins to single dose representatives of three anthelmintic drug classes,
      namely, oxibendazole, pyrantel pamoate, and moxidectin. Thirty ponies aged
      between 1 and 18 years of age were allocated to one of three anthelmintic
      treatments groups. Anthelmintic efficacy was evaluated using the fecal egg count
      reduction test performed weekly between 2 and 8 weeks post-treatment.
      Inflammatory responses were evaluated on days 0, 1, 3, 5, and 14 after treatment
      using hematology, measurement of the acute phase inflammatory markers serum
      amyloid A, fibrinogen, haptoglobin, and iron, and real-time PCR measurement of
      expression of the genes for interleukins 1-beta and -10, tumor necrosis factor
      alpha, and interferon-gamma. There were subtle inflammatory responses to
      treatment, but cytokine expression was significantly associated with the
      interaction term between treatment group and anthelmintic efficacy (P<0.05). Of
      the acute phase markers, only fibrinogen associated with treatment group. The
      findings suggest that systemic inflammatory responses subsequent to anthelmintic
      treatment of cyathostomin infection are minimal. It is possible that this
      response is 'buffered' by anti-inflammatory products of the parasites and/or the
      anti-inflammatory effects of the macrocyclic lactones.

PMID- 24035471
TI  - Controlling Salmonella in live pigs and at slaughter: the Danish experience.

PMID- 24035472
TI  - Temsirolimus improves cytotoxic efficacy of cisplatin and gemcitabine against
      urinary bladder cancer cell lines.
AB  - OBJECTIVES: To analyze the cytotoxic action of temsirolimus using 3 established
      human bladder cancer cell lines and to assess whether temsirolimus potentiates
      the anticancer activity of gemcitabine and cisplatin. METHODS: Temsirolimus (500,
      1,000, 2,000, and 4,000 nM), in isolation, and combined with gemcitabine (100 nM)
      and cisplatin (2.5 ug/ml), was given to 5637, T24, and HT1376 bladder cancer cell
      lines. Cell proliferation, autophagy, early apoptosis, and cell cycle
      distribution were analyzed after a 72-hour period. The expression of mammalian
      target of rapamycin baseline, Akt, and their phosphorylated forms, before and
      after treatment with temsirolimus, was evaluated by immunoblotting. RESULTS:
      Temsirolimus slightly decreased the bladder cancer cell proliferation in all 3
      cell lines. No significant differences in the expression of mammalian target of
      rapamycin, Akt, and their phosphorylated forms because of temsirolimus exposure
      were found in the 3 cell lines. As part of a combined regime along with
      gemcitabine, and especially with cisplatin, there was a more pronounced
      antiproliferative effect. This pattern of response was similar to the other
      parameters analyzed (increased autophagy and apoptosis). Also, in the combined
      regime, an enhanced cell cycle arrest in the G0/G1 phase was observed. The non
      muscle invasive 5637 bladder cancer cell line was most sensitive to both
      combinations. CONCLUSIONS: Temsirolimus makes a moderate contribution in terms of
      cell proliferation, apoptosis, and autophagy. However, it does potentiate the
      activity of gemcitabine and particularly cisplatin. Therefore, cisplatin- or
      gemcitabine-based chemotherapy regimen used in combination with temsirolimus to
      treat bladder cancer represents a novel and valuable treatment option, which
      should be tested for future studies in urinary bladder xenograft models.

PMID- 24035473
TI  - Urine microRNAs as potential noninvasive biomarkers in urologic cancers.
AB  - Micro-ribonucleic acids (miRNAs) are small noncoding RNAs that
      posttranscriptionally regulate gene expression. The ability of miRNAs to inhibit
      translation of oncogenes and tumor suppressors implies that they may be involved
      in carcinogenesis. Our review focuses on the potential of urinary miRNAs to serve
      as biomarkers of urologic cancers. We discuss in detail the recent knowledge
      about the origin of urinary miRNAs, their stability, quality control, and their
      utility as a potential new class of biomarkers in urologic cancer. Finally, we
      summarize the studies focusing on detection and characterization of urinary
      miRNAs as potential biomarkers in bladder, prostate, and kidney cancers. 

PMID- 24035475
TI  - Strategies to prevent reperfusion injury to the brain following intrapartum
      hypoxia-ischemia.
AB  - Hypoxia-ischemia is an infrequent event which may occur prior to or during
      delivery, following a period of decreased placental and/or fetal blood flow.
      Following recovery, a reperfusion phase and secondary energy failure may occur 6
      48 h subsequent to the initial insult. Therapeutic hypothermia may be offered to
      infants at risk for evolving encephalopathy if identified within the 6 h
      therapeutic window, and should be instituted as early as possible for eligible
      infants. Additionally, the clinician must pay close attention to supportive
      measures such as avoidance of hyperthermia, as well as comprehensive management
      of clinical or electrographic seizures, blood pressure, blood glucoses, and
      carbon dioxide levels.

PMID- 24035474
TI  - Genetic polymorphisms in NQO1 and SOD2: interactions with smoking, schistosoma
      infection, and bladder cancer risk in Egypt.
AB  - BACKGROUND: Bladder cancer is the most prevalent form of cancer in men among
      Egyptians, for whom tobacco smoke exposure and Schistosoma haematobium (SH)
      infection are the major risk factors. We hypothesized that functional
      polymorphisms in NAD(P)H: quinone oxidoreductase 1 (NQO1) and superoxide
      dismutase 2 (SOD2), modulators of the effects of reactive oxidative species, can
      influence an individual's susceptibility to these carcinogenic exposures and
      hence the risk of bladder cancer. METHODS: We assessed the effects of potential
      interactions between functional polymorphisms in the NQO1 and SOD2 genes and
      exposure to smoking and SH infection on bladder cancer risk among 902 cases and
      804 population-based controls in Egypt. We used unconditional logistic regression
      to estimate the odds ratios (OR) and confidence intervals (CI) 95%. RESULTS:
      Water pipe and cigarette smoking were more strongly associated with cancer risk
      among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86-10.42])
      as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97-6.74]).
      Conversely, the risk associated with SH infection was higher among the latter (OR
      [CI 95%] = 3.59 [2.21-5.84]) than among the former (OR [CI 95%] = 1.86 [1.33
      2.60]). Polymorphisms in NQO1 genotype showed a similar pattern, but to a much
      lesser extent. The highest odds for having bladder cancer following SH infection
      were observed among individuals with the CC genotypes for both NQO1 and SOD2 (OR
      [CI 95%] = 4.41 [2.32-8.38]). CONCLUSION: Our findings suggest that genetic
      polymorphisms in NQO1 and SOD2 play important roles in the etiology of bladder
      cancer by modulating the effects of known contributing factors such as smoking
      and SH infection.

PMID- 24035476
TI  - Oxygen therapy and oximetry in the delivery room.
AB  - Pulse oximetry is increasingly being used in the delivery room. Expert
      recommendations state that oxygen therapy during newborn resuscitation should be
      guided by pulse oximetry. Obtaining accurate and stable oxygen saturation and
      heart rate information from a pulse oximeter in the delivery room can be
      challenging. Understanding the properties of this device is important in
      overcoming these challenges. This article describes several aspects of pulse
      oximetry use in the delivery room ranging from technical issues with the device
      itself to clinical applications of the technology. 

PMID- 24035477
TI  - Lower limb strength following total knee arthroplasty: a systematic review.
AB  - BACKGROUND: Total knee arthroplasty (TKA) is commonly performed for end-stage
      knee osteoarthritis to relieve pain and improve quality of life. Understanding
      specific muscle weakness following TKA is required in order to develop targeted
      rehabilitation programmes for TKA patients. The aim of this systematic review was
      to determine whether TKA patients have reduced strength in lower limb muscle
      groups compared to controls. METHODS: A search of common scientific databases was
      conducted. A modified published checklist was used to assess the risk of bias. A
      meta-analysis was completed for each lower limb muscle group in three separate
      post-operative time periods (4-6 months, 1-3 years, and >3 years). The GRADE
      approach was used to determine the quality of the evidence. RESULTS: Fifteen
      studies met the inclusion criteria for this review. There was low quality
      evidence for all meta-analyses. The meta-analyses showed that TKA patients had
      weaker quadriceps than the controls at every post-operative time (pooled effect
      sizes between -2.81 and -0.53). The meta-analyses of hamstring strength for
      patients 1-3 years post-operatively also showed patient weakness (pooled effect
      size=-1.87) and no significant difference at >3 years post-operatively (pooled
      effect size=-0.20). CONCLUSION: There was low quality evidence of quadriceps and
      hamstring weakness following TKA. Further research is required to determine if
      other lower limb muscles also display similar muscle weakness. Strategies that
      specifically target strengthening of these muscle groups may need to be
      incorporated in rehabilitation to improve outcomes from TKA. LEVEL OF EVIDENCE:
      I.

PMID- 24035478
TI  - The challenges of stratifying patients for trials in inflammatory bowel disease.
AB  - Immunotherapy with biological agents or small molecules is revolutionising the
      treatment of chronic inflammatory disease in humans; however, a significant
      proportion of patients fail to respond or lose responsiveness. This is
      particularly evident in inflammatory bowel disease (IBD), a group of chronic,
      immune-mediated disorders of the gastrointestinal tract. Different responsiveness
      to treatment in IBD can be explained by substantial disease heterogeneity, which
      is being increasingly recognised by genetic and immunological studies. The
      current enthusiasm for stratified medicine suggests that it may become possible
      to identify clinical, immunological, biochemical or genetic biomarkers to target
      immunotherapy to patients more likely to respond. Here, we identify and highlight
      the opportunities and the challenges of this strategy in the context of IBD. 

PMID- 24035479
TI  - Cocaine self-administration abolishes associative neural encoding in the nucleus
      accumbens necessary for higher-order learning.
AB  - BACKGROUND: Cocaine use is often associated with diminished cognitive function,
      persisting even after abstinence from the drug. Likely targets for these changes
      are the core and shell of the nucleus accumbens (NAc), which are critical for
      mediating the rewarding aspects of drugs of abuse as well as supporting
      associative learning. To understand this deficit, we recorded neural activity in
      the NAc of rats with a history of cocaine self-administration or control subjects
      while they learned Pavlovian first- and second-order associations. METHODS: Rats
      were trained for 2 weeks to self-administer intravenous cocaine or water. Later,
      rats learned a first-order Pavlovian discrimination where a conditioned stimulus
      (CS)+ predicted food, and a control (CS-) did not. Rats then learned a second
      order association where, absent any food reinforcement, a novel cued (SOC+)
      predicted the CS+ and another (SOC-) predicted the CS-. Electrophysiological
      recordings were taken during performance of these tasks in the NAc core and
      shell. RESULTS: Both control subjects and cocaine-experienced rats learned the
      first-order association, but only control subjects learned the second-order
      association. Neural recordings indicated that core and shell neurons encoded task
      relevant information that correlated with behavioral performance, whereas this
      type of encoding was abolished in cocaine-experienced rats. CONCLUSIONS: The NAc
      core and shell perform complementary roles in supporting normal associative
      learning, functions that are impaired after cocaine experience. This impoverished
      encoding of motivational behavior, even after abstinence from the drug, might
      provide a key mechanism to understand why addiction remains a chronically
      relapsing disorder despite repeated attempts at sobriety.

PMID- 24035480
TI  - West Nile viral infection of equids.
AB  - West Nile virus (WNV) is a flavivirus transmitted between certain species of
      birds and mosquito vectors. Tangential infections of equids and subsequent equine
      epizootics have occurred historically. Although the attack rate has been
      estimated to be below 10%, mortality rates can approach 50% in horses that
      present clinical disease. Symptoms are most commonly presenting in the form of
      encephalitis with ataxia as well as limb weakness, recumbency and muscle
      fasciculation. The most effective strategy for prevention of equine disease is
      proper vaccination with one of the numerous commercially available vaccines
      available in North America or the European Union. Recently, WNV has been
      increasingly associated with equine epizootics resulting from novel non-lineage
      1a viruses in expanding geographic areas. However, specific experimental data on
      the virulence of these novel virus strains is lacking and questions remain as to
      the etiology of the expanded epizootics: whether it be a function of inherent
      virulence or ecological and/or climactic factors that could precipitate the
      altered epidemiological patterns observed. 

PMID- 24035481
TI  - Pulmonary artery haemorrhage in newborn calves following bluetongue virus
      serotype 8 experimental infections of pregnant heifers.
AB  - The emergence of bluetongue disease (BT) among livestock in Europe in 2006 raised
      many questions including the occurrence and epidemiological significance of
      foetal infections in cattle. To clarify these aspects, vaccinated and
      unvaccinated pregnant heifers were sequentially infected twice in an isolation
      facility (biosafety level 3) with a northern European outbreak strain of
      Bluetongue virus serotype 8 (BTV-8). The study was terminated 2 months after
      calving with necropsy of the dams and their offspring. The cattle were monitored
      throughout the study by clinical scoring and for the presence of circulating
      neutralising antibodies, and after calving for the presence of infectious virus
      and viral RNA in blood and milk. Four calves, one born from a vaccinated dam and
      three from non-vaccinated ones, that were infected at 120 days of gestation had
      obvious haemorrhage of the pulmonary artery at necropsy. Although haemorrhage of
      the pulmonary artery is highly characteristic of BT, viral RNA was not detected
      in any of these calves. Furthermore, although none of the calves born from
      heifers infected prior to mid-gestation had teratogenic BTV typical brain
      lesions, some had lesions at birth suggestive of in utero BTV infection. Despite
      the lack of viral RNA detection, the presence of haemorrhage of the pulmonary
      artery deserves to be reported as a new observation in the context of the
      multiple investigations having as main subject the BTV placental crossing in
      cattle. 

PMID- 24035482
TI  - [Fertile woman with periodic rectal bleeding].

PMID- 24035483
TI  - Concussion history and reporting rates in elite Irish rugby union players.
AB  - OBJECTIVES: To determine the self-reported, seasonal rates of concussion and the
      reporting practices among Irish rugby union players. DESIGN: Descriptive
      epidemiology study. SETTING: The study was conducted at the training grounds of
      four professional Irish rugby union clubs. PARTICIPANTS: One hundred seventy-two
      players (24.97 +/- 4.11 years of age, 13.49 +/- 5.79 years playing experience)
      gave consent to participate. MAIN OUTCOME MEASURES: Number of concussions
      reported during the 2010-2011 season, reasons for not reporting, and positions of
      concussed players. RESULTS: Forty-five percent of players reported at least one
      concussion during the 2010-2011 season, but only 46.6% of these presented to
      medical staff. The reasons for not reporting their concussions included, not
      thinking the injury was serious enough, and not wanting to be removed from the
      game. The relative proportion of concussions was higher for backs than forwards;
      however, the severity of injury was greater for forwards. Scrum-halves (12.0%)
      and flankers (10.9%) accounted for the majority of concussions reported.
      CONCLUSIONS: The self-reported rate of concussion in elite rugby union players in
      Ireland is higher than reported in other countries or other sports. Many
      concussions remain unreported and, therefore, unmanaged. However, recent changes
      in concussion management guidelines by the International Rugby Board may impact
      future reporting practices of players.

PMID- 24035484
TI  - Treatment of severe subcutaneous emphysema by microdrainage. A case report.

PMID- 24035485
TI  - Bicyclic and tricyclic heterocycle derivatives as histamine H3 receptor
      antagonists for the treatment of obesity.
AB  - A novel series of non-imidazole bicyclic and tricyclic histamine H3 receptor
      antagonists has been discovered. Compound 17 was identified as a centrally
      penetrant molecule with high receptor occupancy which demonstrates robust oral
      activity in rodent models of obesity. In addition compound 17 possesses clean CYP
      and hERG profiles and shows no behavioral changes in the Irwin test. 

PMID- 24035487
TI  - A psychometric analysis of the Clinically Useful Depression Outcome Scale (CUDOS)
      in Spanish patients.
AB  - BACKGROUND: Psychometrically sound and time-efficient scales that measure
      depressive symptoms are essential for research and clinical practice. This study
      was aimed at exploring the psychometric properties of the Spanish version of the
      Clinically Useful Depression Outcome Scale (CUDOS) in a clinical sample. METHOD:
      Participants were 162 patients (72% women) with a mood disorder (86% diagnosed as
      major depressive disorder). Depressive symptoms were assessed by means of the
      CUDOS, the Beck Depression Inventory (BDI), and two interviewer-rated
      instruments: the 17-item Hamilton Depression Rating Scale (HDRS17) and the
      Clinical Global Impression-Severity (CGI-S) scale. Dimensionality, internal
      consistency, test-retest reliability, construct validity, criterion validity, and
      responsiveness to change of the CUDOS were explored. RESULTS: The CUDOS exhibited
      a one-factor structure which accounted for 55.7% of the variance, and excellent
      results for internal consistency (Cronbach's alpha=0.93), for test-retest
      reliability (intraclass correlation coefficient=0.84) and for convergent validity
      [HDRS17 (r=0.77), CGI-S (r=0.73) and BDI (r=0.89)]. The ability of the CUDOS to
      identify patients in remission was high (area under ROC curve=0.96). Its
      responsiveness to change was also highly satisfactory: patients with greater
      clinical improvement showed a greater decrease in CUDOS scores (p<0.001).
      LIMITATIONS: Diagnoses, even though made by expert clinicians, were established
      as part of routine clinical practice. Generalizability of the findings beyond the
      study sample is unknown. CONCLUSIONS: The findings suggest that the Spanish
      version of the CUDOS is valuable as a brief and psychometrically sound self
      report instrument to assess depressive symptoms in research and in clinical
      practice.

PMID- 24035486
TI  - REDOR NMR for drug discovery.
AB  - Rotational-echo double-resonance (REDOR) NMR is a powerful and versatile solid
      state NMR measurement that has been recruited to elucidate drug modes of action
      and to drive the design of new therapeutics. REDOR has been implemented to
      examine composition, structure, and dynamics in diverse macromolecular and whole
      cell systems, including taxol-bound microtubules, enzyme-cofactor-inhibitor
      ternary complexes, and antibiotic-whole-cell complexes. The REDOR approach
      involves the integrated design of specific isotopic labeling strategies and the
      selection of appropriate REDOR experiments. By way of example, this digest
      illustrates the versatility of the REDOR approach, with an emphasis on the
      practical considerations of experimental design and data interpretation. 

PMID- 24035488
TI  - Pattern and predictors of sick leave among users of antidepressants: a Danish
      retrospective register-based cohort study.
AB  - OBJECTIVES: Depression is associated with work absenteeism, reduced productivity,
      and significant personal and societal economic burden. We describe patterns and
      determinants of sick leave among working Danish antidepressant users. METHODS:
      Persons starting antidepressant treatment (January 1, 2004 through December 31,
      2005) were identified from a representative 25% sample of the Danish population
      by linking Danish national registries. Inclusion criteria were age 18-64 years,
      being in the workforce the week prior to the first antidepressant prescription
      (index prescription, IP), and no antidepressant prescription in the year prior to
      the IP. Only sick leaves >2 weeks are centrally registered in Denmark and could
      be assessed. Cox regression analyses identified predictors of sick leave during
      the year following the IP, based on previous history of sick leave and clinical
      and socio-demographic baseline characteristics. RESULTS: In the cohort of 25,908
      (59.7% women), sick leave prevalence increased from 37.5% (year prior to IP) to
      45.3% (year after the IP); 30.7% were on sick leave for >8 weeks. Incidence
      peaked (35.5% of individuals) the week after the IP. Of persons with sick leave
      in the year before the IP, 62.7% were on sick leave the first week after the IP,
      vs 5.7% of those without previous sick leave. Predictors associated with
      increased risk of sick leave among those without previous sick leave were
      unemployment, female gender, age 25-54 years, couples with children, and
      vocational and higher intermediate education (including e.g. teachers and
      nurses). LIMITATIONS: Reasons for sick leave, sick leaves of less than 14 days
      and the indications for antidepressant treatment were unknown. CONCLUSIONS: Sick
      leave was prevalent in persons starting new antidepressant use, often lasting >8
      weeks. Previous sick leave was the strongest predictor of subsequent sick leave.

PMID- 24035489
TI  - Children's risk and resilience following a natural disaster: genetic
      vulnerability, posttraumatic stress, and depression.
AB  - OBJECTIVE: We examined children's risk and resilience following a natural
      disaster, evaluating the role of stress, social support, and two genetic markers:
      the short allele of the serotonin transporter gene (5-HTTLPR), and the met allele
      of the Brain-Derived Neurotrophic Factor (BDNF).Under high levels of hurricane
      exposure or hurricane-related stressors, we expected children displaying the
      markers would report greater symptoms of posttraumatic stress disorder (PTSD) and
      depression than children without these markers. Social support was explored as an
      additional moderating variable. METHOD: Eight months after Hurricane Ike, 116
      children (M age=8.85 years, SD=.89; 54% girls) residing in Galveston, Texas,
      provided saliva samples and completed measures of hurricane exposure and stress,
      and symptoms of PTSD and depression; 80 also completed a social support measure.
      RESULTS: For BDNF, analyses revealed several Gene by Environment interactions;
      greater stress was related to more symptoms of PTSD and depression, and this
      effect was stronger for children with the met allele. No findings emerged for 5
      HTTLPR. Stressors and social support also were associated with children's PTSD
      and depressive symptoms. LIMITATIONS: Findings should be tempered by the
      relatively small sample, especially for analysis that included social support.
      CONCLUSIONS: The met allele (BDNF) may play a role in children's disaster
      reactions. Further research should consider the complex interplay between genes,
      stressors, support, and psychological outcomes over time.

PMID- 24035490
TI  - Hippocampal activation during associative encoding of word pairs and its relation
      to symptomatic improvement in depression: a functional and volumetric MRI study.
AB  - BACKGROUND: Altered emotional memory is one of the core cognitive functions that
      causes and maintains depression. Although many studies have investigated the
      relationship between hippocampal volume, depression and treatment response, no
      studies have investigated the relationship for hippocampal activity.
      Additionally, few studies have examined the relationship between functional and
      structural abnormalities in depression. METHODS: We conducted a functional and
      volumetric MRI study investigating associative encoding of positive, negative and
      neutral word pairs in 13 healthy controls, and 14 untreated depressives. We
      carried out fMRI during a memory-encoding task at baseline. Treatment response
      was clinically assessed six weeks after pharmacotherapy began. Then, we explored
      the relation between brain activation during encoding of each word pair and
      symptomatic improvement. RESULTS: Relative to controls, depressives exhibited
      decreased activity in the left hippocampus during encoding positive word pairs
      and, in contrast, increased activity in the right hippocampus during encoding
      negative or neutral word pairs. Poor response to treatment was associated with
      smaller activation within the left hippocampus during the memory encoding of
      positive word pairs. Overall results were not confounded by hippocampal volume.
      LIMITATIONS: We could not appreciate any disease alteration during the retrieving
      phase. CONCLUSION: We found qualitative differences in hippocampus functioning
      between depressives and healthy controls. In addition, the left hippocampus could
      have an effect on treatment response in depression by contributing to the
      dysfunctional encoding of positive information.

PMID- 24035491
TI  - Affective temperaments and self-harm in adolescents: a cross-sectional study from
      a community sample.
AB  - BACKGROUND: Adolescent self-harm (SH) is a major health problem potentially
      associated with poor outcomes including reduced life expectancy and risk of
      completed suicide in adulthood. Several studies point to the role of possible
      constitutional vulnerabilities that could predispose to this behavior. This study
      sets out to assess the relationship between SH and affective temperaments (AT) in
      adolescents. METHODS: A cross-sectional sample of public school students
      (n=1713), with age limits between 12 and 20, was examined using anonymously
      completed self-report instruments including 'The Lifestyle & Coping
      Questionnaire' and the 'Temperament Evaluation of Memphis, Pisa, Paris and San
      Diego-auto-questionnaire' (TEMPS-A). SH was defined according to strict criteria
      through a two-stage procedure. Statistical significance of associations with SH
      for categorical variables was assessed in bivariate analysis. AT predictors of
      lifetime SH were examined in multivariate logistic regression analyses. RESULTS:
      Lifetime SH was reported by 7.3%, being about three times more frequent in
      females. SH was associated, in both genders, with a significant deviation on
      depressive, cyclothymic and irritable dimensions of TEMPS-A. After multivariate
      logistic regression adjusted to family typology, smoking status, alcohol and drug
      consumption, only depressive temperament remained significantly associated as a
      predictor of SH in both genders. LIMITATIONS: The use of self-rating instruments
      and the cross-sectional nature of the study limit our results. CONCLUSIONS:
      Cyclothymic, irritable and especially depressive temperament might represent an
      important marker of vulnerability to SH in both male and female adolescents.

PMID- 24035492
TI  - Autonomic nervous system function, child behavior, and maternal sensitivity in
      three-year-old children with surgically corrected transposition.
AB  - OBJECTIVES: Explore relationships among autonomic nervous system (ANS) function,
      child behavior, and maternal sensitivity in three-year-old children with
      surgically corrected transposition of the great arteries (TGA) and in children
      healthy at birth. BACKGROUND: Children surviving complex congenital heart defects
      are at risk for behavior problems. ANS function is associated with behavior and
      with maternal sensitivity. METHOD: Child ANS function (heart rate variability)
      and maternal sensitivity (Parent-Child Early Relational Assessment) were measured
      during a challenging task. Mother completed the Child Behavior Checklist. Data
      were analyzed descriptively and graphically. RESULTS: Children with TGA had less
      responsive autonomic function and more behavior problems than healthy children.
      Autonomic function improved with more maternal sensitivity. CONCLUSION:
      Alterations in ANS function may continue years after surgical correction in
      children with TGA, potentially impacting behavioral regulation. Maternal
      sensitivity may be associated with ANS function in this population. Continued
      research on relationships among ANS function, child behavior, and maternal
      sensitivity is warranted.

PMID- 24035493
TI  - The psychological experiences of adult heart transplant recipients: a systematic
      review and meta-summary of qualitative findings.
AB  - BACKGROUND: Psychosocial factors and physical health are associated with
      increased psychological distress post-heart transplant. Integrating findings from
      qualitative studies could highlight mechanisms for how these factors contribute
      to psychological well-being, thus aiding the development of interventions.
      OBJECTIVE: To integrate qualitative findings regarding adult heart transplant
      recipients experiences, such as their emotions, perceptions and attitudes.
      METHODS: A systematic review and meta-summary were conducted. Data from seven
      studies were categorized into 16 abstracted findings. RESULTS: The most prominent
      finding across the studies related to recipients' perceptions of the importance
      of social support. Other prominent findings related to factors that promoted
      psychological well-being, such as faith, optimism and sense of control.
      CONCLUSIONS: Psychological well-being may be improved by enhancing perceived
      control over health and daily life, promoting an optimistic outlook by
      facilitating access to social support from other heart transplant recipients and
      ensuring post-transplant recipient-caregiver partnerships adequately support the
      transition back to independence.

PMID- 24035495
TI  - The efficiency of stepped wedge vs. cluster randomized trials: stepped wedge
      studies do not always require a smaller sample size.

PMID- 24035494
TI  - Life tables adjusted for comorbidity more accurately estimate noncancer survival
      for recently diagnosed cancer patients.
AB  - OBJECTIVES: To provide cancer patients and clinicians with more accurate
      estimates of a patient's life expectancy with respect to noncancer mortality, we
      estimated comorbidity-adjusted life tables and health-adjusted age. STUDY DESIGN
      AND SETTING: Using data from the Surveillance Epidemiology and End Results
      Medicare database, we estimated comorbidity scores that reflect the health status
      of people who are 66 years of age and older in the year before cancer diagnosis.
      Noncancer survival by comorbidity score was estimated for each age, race, and
      sex. Health-adjusted age was estimated by systematically comparing the noncancer
      survival models with US life tables. RESULTS: Comorbidity, cancer status, sex,
      and race are all important predictors of noncancer survival; however, their
      relative impact on noncancer survival decreases as age increases. Survival models
      by comorbidity better predicted noncancer survival than the US life tables. The
      health-adjusted age and national life tables can be consulted to provide an
      approximate estimate of a person's life expectancy, for example, the health
      adjusted age of a black man aged 75 years with no comorbidities is 67 years,
      giving him a life expectancy of 13 years. CONCLUSION: The health-adjusted age and
      the life tables adjusted by age, race, sex, and comorbidity can provide important
      information to facilitate decision making about treatment for cancer and other
      conditions.

PMID- 24035496
TI  - Phospholipase C-beta1 and schizophrenia-related behaviors.
AB  - Abnormal expression patterns of phospholipase C-beta1(PLC-beta1) in specific
      brain areas of patients with schizophrenia, and its high genetic linkage to the
      disorder implicated a pathogenetical involvement of PLC-beta1 signaling system.
      The schizophrenia-related behavioral phenotypes displayed in the mutant mice
      lacking PLC-beta1 (PLC-beta1 KO) suggested that PLCbeta1-linked signaling
      pathways may be involved in the neural system whose function is disrupted in the
      pathogenesis of schizophrenia. In the brain, PLC-beta1 is known to be linked to
      muscarinic acetylcholine receptors, metabotropic glutamatergic, serotonergic, and
      oxytocinergic systems. The objective of this review is to provide an overview of
      the current knowledge regarding these schizophrenia-related behaviors and discuss
      the probable ways in which PLC-beta1signalling can be involved in the neural
      mechanisms for each behavior, which may help suggest future directions for
      research in this area. 

PMID- 24035497
TI  - Circular intronic long noncoding RNAs.
AB  - We describe the identification and characterization of circular intronic long
      noncoding RNAs in human cells, which accumulate owing to a failure in
      debranching. The formation of such circular intronic RNAs (ciRNAs) can be
      recapitulated using expression vectors, and their processing depends on a
      consensus motif containing a 7 nt GU-rich element near the 5' splice site and an
      11 nt C-rich element close to the branchpoint site. In addition, we show that
      ciRNAs are abundant in the nucleus and have little enrichment for microRNA target
      sites. Importantly, knockdown of ciRNAs led to the reduced expression of their
      parent genes. One abundant such RNA, ci-ankrd52, largely accumulates to its sites
      of transcription, associates with elongation Pol II machinery, and acts as a
      positive regulator of Pol II transcription. This study thus suggests a cis
      regulatory role of noncoding intronic transcripts on their parent coding genes. 

PMID- 24035498
TI  - Parallel SCF adaptor capture proteomics reveals a role for SCFFBXL17 in NRF2
      activation via BACH1 repressor turnover.
AB  - Modular cullin-RING E3 ubiquitin ligases (CRLs) use substrate binding adaptor
      proteins to specify target ubiquitylation. Many of the ~200 human CRL adaptor
      proteins remain poorly studied due to a shortage of efficient methods to identify
      biologically relevant substrates. Here, we report the development of parallel
      adaptor capture (PAC) proteomics and its use to systematically identify candidate
      targets for the leucine-rich repeat family of F-box proteins (FBXLs) that
      function with SKP1-CUL1-F-box protein (SCF) E3s. In validation experiments, we
      identify the unstudied F-box protein FBXL17 as a regulator of the NFR2 oxidative
      stress pathway. We demonstrate that FBXL17 controls the transcription of the NRF2
      target HMOX1 via turnover of the transcriptional repressor BACH1 in the absence
      or presence of extrinsic oxidative stress. This work identifies a role for
      SCF(FBXL17) in controlling the threshold for NRF2-dependent gene activation and
      provides a framework for elucidating the functions of CRL adaptor proteins.

PMID- 24035500
TI  - TORC2 signaling pathway guarantees genome stability in the face of DNA strand
      breaks.
AB  - A chemicogenetic screen was performed in budding yeast mutants that have a
      weakened replication stress response. This identified an inhibitor of target of
      rapamycin (TOR) complexes 1 and 2 that selectively enhances the sensitivity of
      sgs1Delta cells to hydroxyurea and camptothecin. More importantly, the inhibitor
      has strong synthetic lethality in combination with either the break-inducing
      antibiotic Zeocin or ionizing radiation, independent of the strain background.
      Lethality correlates with a rapid fragmentation of chromosomes that occurs only
      when TORC2, but not TORC1, is repressed. Genetic inhibition of Tor2 kinase, or
      its downstream effector kinases Ypk1/Ypk2, conferred similar synergistic effects
      in the presence of Zeocin. Given that Ypk1/Ypk2 controls the actin cytoskeleton,
      we tested the effects of actin modulators latrunculin A and jasplakinolide. These
      phenocopy TORC2 inhibition on Zeocin, although modulation of calcineurin
      sensitive transcription does not. These results implicate TORC2-mediated actin
      filament regulation in the survival of low levels of DNA damage.

PMID- 24035499
TI  - Proteasomes activate aggresome disassembly and clearance by producing unanchored
      ubiquitin chains.
AB  - Aberrant protein aggregation is a dominant pathological feature in
      neurodegenerative diseases. Protein aggregates cannot be processed by the
      proteasome; instead, they are frequently concentrated to the aggresome, a
      perinuclear inclusion body, and subsequently removed by autophagy. Paradoxically,
      proteasomes are also concentrated at aggresomes and other related inclusion
      bodies prevalent in neurodegenerative disease. Here, we show that proteasomes are
      crucial components in aggresome clearance. The disassembly and disposal of
      aggresomes requires Poh1, a proteasomal deubiquitinating enzyme that cleaves
      ubiquitinated proteins and releases ubiquitin chains. In Poh1-deficient cells,
      aggresome clearance is blocked. Remarkably, microinjection of free lysine (K) 63
      linked ubiquitin chains restores aggresome degradation. We present evidence that
      free ubiquitin chains produced by Poh1 bind and activate the deacetylase HDAC6,
      which, in turn, stimulates actinomyosin- and autophagy-dependent aggresome
      processing. Thus, unanchored ubiquitin chains are key signaling molecules that
      connect and coordinate the proteasome and autophagy to eliminate toxic protein
      aggregates.

PMID- 24035501
TI  - The C-terminal domain of Rpb1 functions on other RNA polymerase II subunits.
AB  - The C-terminal domain (CTD) of Rpb1, the largest subunit of RNA polymerase II
      (RNApII), coordinates recruitment of RNA- and chromatin-modifying factors to
      transcription complexes. It is unclear whether the CTD communicates with the
      catalytic core region of Rpb1 and thus must be physically connected, or instead
      can function as an independent domain. To address this question, CTD was
      transferred to other RNApII subunits. Fusions to Rpb4 or Rpb6, two RNApII
      subunits located near the original position of CTD, support viability in a strain
      carrying a truncated Rpb1. In contrast, CTD fusion to Rpb9 on the other side of
      RNApII does not. Rpb4-CTD and Rpb6-CTD proteins are functional for
      phosphorylation and recruitment of various factors, albeit with some restrictions
      and minor defects. Normal CTD functions are not transferred to RNApI or RNApIII
      by Rbp6-CTD. These results show that, with some spatial constraints, CTD can
      function even when disconnected from Rpb1.

PMID- 24035503
TI  - The solitary pulmonary nodule in patients with previous cancer history: results
      of surgical treatment.
AB  - BACKGROUND: The present study was carried out to evaluate the characteristics of
      solitary pulmonary nodule (SPN) in patients with previous cancer(s) and to
      analyse the outcome of its surgical treatment. METHODS: We retrospectively
      analysed 131 patients with history of previous malignancy submitted to lung
      surgery for new identified SPN between January 2004 and December 2009. RESULTS:
      The diagnosis was metastasis in 65 patients, primary lung cancer in 57, benign
      lesion in 9. Primary lung cancers were significantly larger, had higher maxSUV at
      CT-PET scanning, occurred after a longer disease-free interval in patients older
      and with worse lung function when compared with metastatic lesions. Overall
      survival at 5-year was 67% for benign lesions, 62% for primary lung cancer, 48%
      for metastatic disease. Histological subtype, SPN diameter less than 2 cm and DFI
      >36 months were factors influencing long-term prognosis of metastatic patients.
      Histological subtype and pathological staging were factors influencing long-term
      outcome of primary lung cancer patients. DISCUSSION: Surgical resection of
      solitary pulmonary nodule is essential in patients with history of previous
      cancer to rule out benign lesions, to offer diagnostic confirmation and local
      control of the disease in metastatic tumours and to correctly stage and treat
      primary lung cancer.

PMID- 24035502
TI  - Morbidity and mortality outcomes of cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy in patients with primary and recurrent advanced
      ovarian cancer.
AB  - BACKGROUND: The aim of this study is to report the perioperative outcomes of CRS
      and HIPEC from a single institution and review those factors that are associated
      with a poor perioperative outcome in patients with peritoneal dissemination from
      primary or recurrent ovarian cancer. PATIENTS AND METHOD: A retrospective cohort
      study setting was conducted in a third level hospital peritoneal surface
      malignancy program. Ninety one patients diagnosed with ovarian peritoneal
      carcinomatosis, primary and recurrent without extraperitoneal metastasis were
      included for cytoreductive surgery and HIPEC with paclitaxel. We analyzed the
      postoperative morbidity rates and a univariate and multivariate analysis of
      factors associated with overall (grade I-IV) and major (grade III-IV)
      postoperative morbidity were performed. RESULTS: Peritoneal Cancer Index (PCI)
      upper than 12 (OR = 2.942 95%: 1.892-9.594 p = 0.044) was an independent factor
      associated with the occurrence of I-IV postoperative morbidity. Regarding major
      complications (grade III-IV), on multivariate analysis, in addition to PCI >12
      (OR = 6.692, 95% CI: 1974-45, 674, p = 0.032), the need to carry out intestinal
      resection (OR = 4.987, 95% CI: 1350-27, 620, p = 0.046) was an independent factor
      related with major morbidity (grade III-IV). CONCLUSIONS: The use of HIPEC after
      aggressive cytoreductive surgery in patients with ovarian cancer with peritoneal
      dissemination can be performed with acceptable postoperative morbidity rates.
      Knowledge of the factors associated with the onset of these postoperative adverse
      events allows better management of the same and offers the patient a safe
      procedure.

PMID- 24035504
TI  - Trends in diagnostic CT among fee-for-service enrollees, 2000-2011.
AB  - OBJECTIVES: To examine trends in the use of diagnostic CT in aggregate and for 4
      major body regions (abdomen/pelvis, head/neck, chest, and spine) in an 11-year US
      nationwide analysis. METHODS: We summarize records from a large, mostly fee-for
      service insurance claims database from 2000 to 2011. RESULTS: Rates of diagnostic
      CT have increased substantially from 2000 to 2011; however, changes in rates are
      disparate for different age groups and body regions. As others have shown, there
      has been a notable increase in use of diagnostic CT from 2000 to 2011. However,
      from 2009 to 2011, diagnostic CT studies of the chest, abdomen/pelvis, and
      head/neck have leveled off or decreased, whereas CTs of the spine show a
      continued increase in many groups. CONCLUSIONS: In general, the increase in the
      rate of CT study performance has slowed, whereas spine CT continued to escalate.
      Future research should consider whether the increase in use of spine CT leads to
      a benefit that outweighs the risk associated with the increased population-level
      cancer risk.

PMID- 24035506
TI  - Assessment of cardiac troponin elevation with an unclear etiology.

PMID- 24035505
TI  - Biphasic versus monophasic defibrillation in out-of-hospital cardiac arrest: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Biphasic defibrillation is more effective than monophasic one in
      controlled in-hospital conditions. The present review evaluated the performance
      of both waveforms in the defibrillation of patients of out-of-hospital cardiac
      arrest (OHCA) with initial ventricular fibrillation (Vf) rhythm under the context
      of current recommendations for cardiopulmonary resuscitation. METHODS: From
      inception to June 2012, Medline, Embase, and the Cochrane Central Register of
      Controlled Trials were searched systemically for randomized controlled trials
      (RCTs) and observational cohort studies that compared the effects of biphasic and
      monophasic shocks on Vf termination, return of spontaneous circulation (ROSC),
      and survival to hospital discharge in OHCA patients with initial Vf rhythm. No
      restrictions were applied regarding language, population, or publication year.
      RESULTS: Four RCTs including 572 patients were identified from 131 potentially
      relevant references for meta-analysis. The synthesis of these RCTs yielded fixed
      effect pooled risk ratios (RRs) for biphasic and monophasic waveforms on Vf
      termination survival to hospital discharge (RR, 1.14; 95% CI, [0.84-1.54]).
      CONCLUSION: Biphasic waveforms did not seem superior to monophasic ones with
      respect to Vf termination, ROSC, or survival to hospital discharge in OHCA
      patients with initial Vf rhythm under the context of current guidelines. However,
      most trials were conducted in accordance with previous guidelines for
      cardiopulmonary resuscitation. Therefore, further trials are needed to clarify
      this issue.

PMID- 24035507
TI  - Improvement in chest compression quality using a feedback device (CPRmeter): a
      simulation randomized crossover study.
AB  - PURPOSES: Cardiac arrest survival depends on celerity and efficiency of life
      support action. Guidelines emphasized the chest compression (CC) quality and
      feedback devices are encouraged. The purpose is to study the impact of the
      CPRmeter feedback device on resuscitation performed by untrained rescuers. BASIC
      PROCEDURES: This is a prospective randomized crossover study on manikins (Resusci
      Anne). One hundred and forty four students inexperienced in cardiopulmonary
      resuscitation representing untrained rescuers were included. Participants
      performed 2 minutes of CC without interruption with (group G) or without (group
      B) feedback. Four months passed between the 2 crossover phases to avoid
      resilience effect. Data collected by the CPRmeter device were: CC rate, depth and
      release. MAIN FINDINGS: Efficient CC rate ([simultaneous and correct CC rate,
      depth and release] primary outcome) (absolute difference [95% CI]) was
      significantly improved in group G (71%) compared to group B (26%; [45 {36-55}]; P
      < .0001). Adequate depth rate (>38 mm) was significantly improved in group G
      (85%) compared to group B (43%; [42 {33-52}]; P < .0001). Adequate CC rate (90
      120/min) was significantly improved in group G (81%) compared to group B (56%;
      [25 {15-35}]; P < .0001). The average CC rate and depth in group G were
      significantly less dispersed around the mean compared to group B (test of
      variance P < .007; P < .015 respectively). PRINCIPAL CONCLUSIONS: The use of the
      CPRmeter significantly improved CC quality performed by students inexperienced in
      cardiopulmonary resuscitation.

PMID- 24035508
TI  - Understanding the adsorptive and photoactivity properties of Ag-graphene oxide
      nanocomposites.
AB  - Nanocomposites of graphene oxide (GO) and silver nanoparticles (AgNPs) were
      synthetized using a practical photochemical silver functionalization. Their
      photocatalytic activities were evaluated with two dyes, Rhodamine B and Indigo
      Carmine, under visible-light irradiation. The prepared nanocomposites were
      characterized by HRTEM, FESEM, XRD, Raman, FTIR and UV-vis absorption
      spectroscopy. These nanocomposites present new defect domains of sp(3) type in
      combination with several graphitic functional groups that act as nucleation sites
      for anchoring AgNPs, while the sp(2)-sp(3) edge defects domains of GO generate
      the photoactivity. Furthermore, their photocatalytic performances are governed by
      their large adsorption capacity, and strong interaction with dye chromophores. A
      comprehensive photocatalytic way underlying the importance of adsorption is
      suggested to explain the low visible-light responsive photoactivity of the AgNPs
      GO nanocomposites and the possible binding-site saturation. Then, the usage of
      H2SO4 allows the production of ionic species and helps to confirm the strong
      adsorption of both dyes. The ability to synthesize AgNPs-GO nanocomposites with
      extensive adsorptive capacity is certainly of interest for the efficient removal
      of hazardous materials. 

PMID- 24035509
TI  - Modelling the emerging pollutant diclofenac with the GREAT-ER model: application
      to the Llobregat River Basin.
AB  - The present research aims at giving an insight into the increasingly important
      issue of water pollution due to emerging contaminants. In particular, the source
      and fate of the non-steroidal anti-inflammatory drug diclofenac have been
      analyzed at catchment scale for the Llobregat River in Catalonia (Spain). In
      fact, water from the Llobregat River is used to supply a significant part of the
      Metropolitan Area of Barcelona. At the same time, 59 wastewater treatment plants
      discharge into this basin. GREAT-ER model has been implemented in this basin in
      order to reproduce a static balance for this pollutant for two field campaigns
      data set. The results highlighted the ability of GREAT-ER to simulate the
      diclofenac concentrations in the Llobregat Catchment; however, this study also
      pointed out the urgent need for longer time series of observed data and a better
      knowledge of wastewater plants outputs and their parameterization in order to
      obtain more reliable results. 

PMID- 24035510
TI  - Y-chromosomal analysis identifies the skeletal remains of Swiss national hero
      Jorg Jenatsch (1596-1639).
AB  - Jorg Jenatsch was a Swiss defender of independence and a fighter for liberty in
      the 17th century. With the help of three living male members of the Jenatsch
      family, we successfully identified a skeleton exhumed from Chur cathedral as the
      remains of Jorg Jenatsch. Our conclusion was based upon complete Y-STR and Y-SNP
      profiles that could be generated by replicate analyses of a bone sample available
      to us. The skeleton and the three living family members carried the same Y-SNP
      haplogroup, but were discordant at three of 23 Y-STR loci. This notwithstanding,
      conservative biostatistical evaluation of the data suggests that the Chur
      skeleton is at least 20 times more likely than not to be Jorg Jenatsch. 

PMID- 24035511
TI  - Single-cell quantitative HER2 measurement identifies heterogeneity and distinct
      subgroups within traditionally defined HER2-positive patients.
AB  - Human epidermal growth factor receptor 2 (HER2) is an important biomarker for
      breast and gastric cancer prognosis and patient treatment decisions. HER2
      positivity, as defined by IHC or fluorescent in situ hybridization testing,
      remains an imprecise predictor of patient response to HER2-targeted therapies.
      Challenges to correct HER2 assessment and patient stratification include
      intratumoral heterogeneity, lack of quantitative and/or objective assays, and
      differences between measuring HER2 amplification at the protein versus gene
      level. We developed a novel immunofluorescence method for quantitation of HER2
      protein expression at the single-cell level on FFPE patient samples. Our assay
      uses automated image analysis to identify and classify tumor versus non-tumor
      cells, as well as quantitate the HER2 staining for each tumor cell. The HER2
      staining level is converted to HER2 protein expression using a standard cell
      pellet array stained in parallel with the tissue sample. This approach allows
      assessment of HER2 expression and heterogeneity within a tissue section at the
      single-cell level. By using this assay, we identified distinct subgroups of HER2
      heterogeneity within traditional definitions of HER2 positivity in both breast
      and gastric cancers. Quantitative assessment of intratumoral HER2 heterogeneity
      may offer an opportunity to improve the identification of patients likely to
      respond to HER2-targeted therapies. The broad applicability of the assay was
      demonstrated by measuring HER2 expression profiles on multiple tumor types, and
      on normal and diseased heart tissues.

PMID- 24035512
TI  - Epithelial calreticulin up-regulation promotes profibrotic responses and
      tubulointerstitial fibrosis development.
AB  - Renal fibrosis is the common anatomical feature underlying the progression of
      chronic kidney disease, a leading cause of morbidity and mortality worldwide. In
      a previous study, we demonstrated that during development of renal fibrosis in a
      rat model of unilateral ureteric obstruction, calreticulin (CRT) is up-regulated
      in tubular epithelial cells (TECs). In the present study, we used in vitro and in
      vivo approaches to examine the role of CRT in TECs and its contribution to the
      progression of fibrosis. In cultured renal TECs, CRT overexpression induced
      acquisition of an altered, profibrotic cellular phenotype. Consistently, the
      opposite effects were observed for CRT knockdown. Subsequently, we confirmed that
      critical changes observed in vitro were also apparent in tubular cells in vivo in
      the animal model of unilateral ureteric obstruction. In agreement with these
      results, we demonstrate that substantial (50%) reduction in the expression of CRT
      reduced the development of tubulointerstitial fibrosis at a comparable level
      through regulation of inflammation, transcriptional activation, transforming
      growth factor beta1-associated effects, and apoptosis. In summary, our findings
      establish that CRT is critically involved in the molecular mechanisms that drive
      renal fibrosis progression and indicate that inhibition of CRT expression might
      be a therapeutic target for reduction of fibrosis and chronic kidney disease
      development.

PMID- 24035513
TI  - Renal heparan sulfate proteoglycans modulate fibroblast growth factor 2 signaling
      in experimental chronic transplant dysfunction.
AB  - Depending on the glycan structure, proteoglycans can act as coreceptors for
      growth factors. We hypothesized that proteoglycans and their growth factor
      ligands orchestrate tissue remodeling in chronic transplant dysfunction. We have
      previously shown perlecan to be selectively up-regulated in the glomeruli and
      arteries in a rat renal transplantation model. Using the same model, here we
      present quantitative RT-PCR profiling data on proteoglycans and growth factors
      from laser-microdissected glomeruli, arterial tunicae mediae, and neointimae at
      12 weeks after transplantation. In glomeruli and neointimae of allografts,
      selective induction of the matrix heparan sulfate proteoglycan perlecan was
      observed, along with massive accumulation of fibroblast growth factor 2 (FGF2).
      Profiling the heparan sulfate polysaccharide side chains revealed conversion from
      a non-FGF2-binding heparan sulfate phenotype in control and isografted kidneys
      toward a FGF2-binding phenotype in allografts. In vitro experiments with perlecan
      positive rat mesangial cells showed that FGF2-induced proliferation is dependent
      on sulfation and can be inhibited by exogenously added heparan sulfate. These
      findings indicate that matrix proteoglycans such as perlecan serve as functional
      docking platforms for FGF2 in chronic transplant dysfunction. We speculate that
      heparin-like glycomimetics could be a promising intervention to retard
      development of glomerulosclerosis and neointima formation in chronic transplant
      dysfunction.

PMID- 24035514
TI  - TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues
      of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides.
AB  - A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4
      methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists.
      Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of
      capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a
      rat neuropathic pain model. Consistent with its action in vitro being through
      TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking
      analysis of 24S with our hTRPV1 homology model was performed to identify its
      binding mode. 

PMID- 24035516
TI  - Transcriptomic analysis of UV-treated rice leaves reveals UV-induced phytoalexin
      biosynthetic pathways and their regulatory networks in rice.
AB  - Rice produces diterpenoid and flavonoid phytoalexins for defense against pathogen
      attack. The production of phytoalexins in rice is also induced by UV-irradiation.
      To understand the metabolic networks involved in UV-induced phytoalexin
      biosynthesis and their regulation, phytochemical and transcriptomic analyses of
      UV-treated rice leaves were performed. In response to UV treatment, the
      accumulation of flavonoids was observed in rice leaves, which may serve as
      antioxidants against UV-induced oxidative stress. The phytochemical analysis
      confirmed sakuranetin accumulation and also demonstrated the induction of
      phenylamide synthesis in rice leaves by UV-irradiation. Transcriptomic analysis
      established that aromatic amino acid biosynthetic genes were immediately up
      regulated after UV treatment. The genes involved in the phenylpropanoid pathway
      and flavonoid biosynthesis were also up-regulated. These findings suggest that
      the aromatic amino acid and flavonoid biosynthetic pathways are coordinately
      activated for the production of flavonoids and phenolic phytoalexins such as
      sakuranetin and phenylamides. An in silico analysis of UV-induced O
      methyltransferase and acyltransferase genes suggested that these genes may be
      implicated in sakuranetin and phenylamide synthesis, respectively. The
      transcriptomic analysis also showed up-regulation of both methylerythritol
      phosphate pathway and the diterpenoid phytoalexin biosynthetic genes in response
      to UV treatment. A functional gene network analysis of phytoalexin biosynthetic
      and UV-induced genes for signaling components and transcription factors using
      RiceNet suggested that regulatory networks comprising signal perceiving receptor
      kinases, G-proteins, signal transducing mitogen-activated protein kinases and
      calcium signaling components, and transcription factors control flavonoid and
      phytoalexin biosynthesis in rice leaves under UV-C stress conditions. 

PMID- 24035517
TI  - Editorial comment.

PMID- 24035515
TI  - Radiochemical and radiobiological assessment of a pyridyl-S-cysteine
      functionalized bombesin derivative labeled with the (99m)Tc(CO)3(+) core.
AB  - Bombesin is a neuropeptide widely studied due to its ability to target various
      types of cancers. Technetium-99m on the other hand is ideal for diagnostic tumor
      targeting. The aim of the present study is the investigation of the coupling of
      the ligand (S)-(2-(2'-pyridyl)ethyl)-d,l-cysteine with the BN-peptide Gln-Arg-Leu
      Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met(CONH2) through the spacer aminohexanoic
      acidand the labeling of the resulting derivative MBN with the synthon
      [M(CO)3(H2O)3](+) (M=(99m)Tc, Re). The peptide was synthesized according to the
      SPPS method, purified and characterized by ESI-MS. The new (99m)Tc-labeled
      biomolecule was stable in vitro, showed high affinity for the human GRP receptor
      expressed in PC3 cells and the rate of internalization was found to be time
      dependent tissue distribution of the radiopeptide was evaluated in normal mice
      and in prostate cancer experimental models and significant radioactivity uptake
      was observed in the pancreas of normal mice as well as in PC3 tumors. Dynamic
      studies of the radiopeptide showed satisfactory tumor images. 

PMID- 24035518
TI  - The profile of women who consult midwives in Australia.
AB  - BACKGROUND: There is no Australian data on the characteristics of women who
      consult with midwives. AIM: To determine the profile of women who consult
      midwives in Australia. METHODS: This cross-sectional research was conducted as
      part of the Australian Longitudinal Study on Women's Health (ALSWH). Participants
      were the younger (31-36 years) cohort of the ALSWH who completed a survey in
      2009, and indicated that they were currently pregnant (n=801). The main outcome
      measure was consultation with a midwife. FINDINGS: Of the 801 women who indicated
      that they were currently pregnant at the time of the survey, 19%, 42%, and 70% of
      women in the first, second and third trimesters respectively had consulted with a
      midwife. Women were more likely to consult a midwife if they: also consulted with
      a hospital doctor (OR=2.70, 95% CI: 1.66, 4.40); also consulted with a
      complementary and alternative medicine practitioner (OR=1.94, 95% CI: 1.25,
      3.03); were depressed (OR=1.84, 95% CI: 1.03, 3.28); constipated (OR=1.80, 95%
      CI: 1.04, 3.13); or had been diagnosed or treated for hypertension during
      pregnancy (OR=2.78, 95% CI: 1.27, 6.09). Women were less likely (OR=0.34, 95% CI:
      0.21, 0.56) to consult with a midwife if they had private health insurance.
      CONCLUSION: Women were more likely to consult with midwives in conjunction with
      consultations with hospital doctors or complementary and alternative medicine
      practitioners. Women with private health insurance were less likely to consult
      midwives. More research is necessary to determine the implications of the lack of
      midwifery care for these women.

PMID- 24035519
TI  - Discrimination against 15N among recombinant inbred lines of Phaseolus vulgaris
      L. contrasting in phosphorus use efficiency for nitrogen fixation.
AB  - Although isotopic discrimination processes during nitrogen (N) transformations
      influence the outcome of (15)N based quantification of N2 fixation in legumes,
      little attention has been given to the effects of genotypic variability and
      environmental constraints such as phosphorus (P) deficiency, on discrimination
      against (15)N during N2 fixation. In this study, six Phaseolus vulgaris
      recombinant inbred lines (RILs), i.e. RILs 115, 104, 34 (P deficiency tolerant)
      and 147, 83, 70 (P deficiency sensitive), were inoculated with Rhizobium tropici
      CIAT899, and hydroaeroponically grown with P-sufficient (250 MUmol P plant(-1)
      week(-1)) versus P-deficient (75 MUmol P plant(-1) week(-1)) supply. Two harvests
      were done at 15 (before nodule functioning) and 42 (flowering stage) days after
      transplanting. Nodulation, plant biomass, P and N contents, and the ratios of
      (15)N over total N content ((15)N/Nt) for shoots, roots and nodules were
      determined. The results showed lower (15)N/Nt in shoots than in roots, both being
      much lower than in nodules. P deficiency caused a larger decrease in (15)N/Nt in
      shoots (-0.18%) than in nodules (-0.11%) for all of the genotypes, and the
      decrease in shoots was greatest for RILs 34 (-0.33%) and 104 (-0.25%). Nodule
      (15)N/Nt was significantly related to both the quantity of N2 fixed
      (R(2)=0.96***) and the P content of nodules (R(2)=0.66*). We conclude that the
      discrimination against (15)N in the legume N2-fixing symbiosis of common bean
      with R. tropici CIAT899 is affected by P nutrition and plant genotype, and that
      the (15)N/Nt in nodules may be used to screen for genotypic variation in P use
      efficiency for N2 fixation.

PMID- 24035520
TI  - Development and feasibility of a senior elastic band exercise program for aged
      adults: a descriptive evaluation survey.
AB  - OBJECTIVE: This study aimed to develop a tailored elastic band exercise program
      for aged adults (persons 65 years and older), to evaluate the feasibility of a
      program, and to determine appropriate elastic band exercise frequencies and
      preferences of aged adults. METHODS: This study had 2 phases. In phase I, 11
      professional experts were consulted to develop the Senior Elastic Band (SEB)
      exercise program. They responded to detailed description and demonstrations of
      the program contained on either a hard copy or a DVD. In phase II, 20
      participants 65 years or older were interviewed for their feedback on the SEB
      after participating in 1 month of instructor-led SEB group practice. Both
      quantitative and qualitative strategies were included in the subject evaluation.
      The quantitative evaluation results were analyzed using descriptive statistics of
      mean and SD. The qualitative revision suggestions were critically analyzed and
      summarized using content analysis to revise the program. RESULTS: Both the
      experts in phase I and the senior participants in phase II rated the SEB highly
      and commented that the program was feasible, safe, suitable, and helpful. The
      participants further suggested practicing SEB 3 times per week for 60 minutes per
      session in a group of 20 to 29 people. CONCLUSIONS: Based on the feedback from
      the expert panel, the final SEB included 3 phases with 20 movements. The program
      took 40 minutes to complete. The SEB program was supported by the 11 experts with
      5 professional backgrounds and was well accepted by a small group of community
      seniors. The participants expressed that the program was feasible, was
      manageable, and could be helpful to their health promotion.

PMID- 24035521
TI  - Alterations in cortical and cerebellar motor processing in subclinical neck pain
      patients following spinal manipulation.
AB  - OBJECTIVE: The purpose of this study was investigate whether there are
      alterations in cerebellar output in a subclinical neck pain (SCNP) group and
      whether spinal manipulation before motor sequence learning might restore the
      baseline functional relationship between the cerebellum and motor cortex.
      METHODS: Ten volunteers were tested with SCNP using transcranial magnetic
      stimulation before and after a combined intervention of spinal manipulation and
      motor sequence learning. In a separate experiment, we tested 10 healthy controls
      using the same measures before and after motor sequence learning. Our
      transcranial magnetic stimulation measurements included short-interval
      intracortical inhibition, long-interval intracortical inhibition, and cerebellar
      inhibition (CBI). RESULTS: The SCNP group showed a significant improvement in
      task performance as indicated by a 19% decrease in mean reaction time (P <
      .0001), which occurred concurrently with a decrease in CBI following the combined
      spinal manipulation and motor sequence learning intervention (F1,6 = 7.92, P <
      .05). The control group also showed an improvement in task performance as
      indicated by a 25% increase in reaction time (P < .001) with no changes to CBI.
      CONCLUSIONS: Subclinical neck pain patients have altered CBI when compared with
      healthy controls, and spinal manipulation before a motor sequence learning task
      changes the CBI pattern to one similar to healthy controls.

PMID- 24035522
TI  - Safety and efficacy of G-CSF mobilization and collection of autologous peripheral
      blood stem cells in children with cerebral palsy.
AB  - We hypothesized that mobilized peripheral blood stem cells (PBSCs) could be
      useful for treating neurological impairments and therefore assessed the safety of
      administering G-CSF followed by collecting PBSC in children with cerebral palsy
      (CP). G-CSF (10 MUg/kg/day) was administered subcutaneously for 5 days, and
      apheresis was performed to collect PBSC via central venous catheter. G-CSF
      related events occurred in 3 patients (fever in 2, irritability in 1). No
      catheter-related complications were reported. None of the patients needed
      platelet transfusion or calcium replacement during apheresis. Mobilization with G
      CSF followed by PBSC collection appears to be safe and feasible in CP children.

PMID- 24035523
TI  - [Functional results after temporomandibular joint reconstruction using a total
      joint prosthesis (part II)].
AB  - INTRODUCTION: Temporomandibular joint (TMJ) disorders are usually managed
      medically. But partial or total reconstruction may be indicated according to the
      severity and the functional impairment. We assessed the functional results after
      total TMJ reconstruction using the Biomet Microfixation(r) prosthesis
      (Jacksonville, FL, USA). MATERIAL AND METHODS: We reviewed the files of patients
      having undergone reconstruction, between 2009 and 2010, with a total TMJ
      prosthesis. We analyzed the pre- and postoperative mouth opening, the pre- and
      postoperative occlusion, pre- and postoperative pain according to a simple spoken
      scale ranging from 0 (no pain) to 4 (severe pain). RESULTS: Twelve total TMJ
      prostheses were placed in five women and three men (mean age 49.2 years).
      Restriction of mouth opening was the first cause of consultation. The etiology
      was trauma for four patients. Three patients had preoperative malocclusion. Four
      patients had bilateral reconstruction. Preoperative pain ranged between 2 and 4.
      The average initial mouth opening was 17.8mm. There was neither infection nor any
      major complication. No prosthesis was removed. The mean follow-up was 18.5
      months. At the end of the study, pain ranged between 0 and 2. All patients with
      preoperative malocclusion resumed an Angle class I postoperatively. The average
      postoperative mouth opening was 39.5mm. DISCUSSION: Total TMJ reconstruction with
      the Biomet Microfixation(r) prosthesis improves mouth opening and reduces pain.

PMID- 24035524
TI  - Contrast-enhanced multiphasic CT and MRI findings of adenosquamous carcinoma of
      the pancreas.
AB  - OBJECTIVE: The objective was to retrospectively study computed tomography (CT)
      and magnetic resonance imaging (MRI) findings of adenosquamous carcinoma of the
      pancreas (PASC). MATERIALS AND METHODS: Twelve patients (six women and six men;
      mean age, 61.3 years; range, 47-78 years) who presented with PASC as documented
      by pathologic examination underwent CT (n=10) or both CT and MRI (n=2)
      examination. Two radiologists evaluated the images and determined the location,
      size, margin, internal attenuation or signal intensity, contrast enhancement, and
      pattern for each tumor. Additionally, the presence of poorly enhanced areas,
      upstream main pancreatic duct (MPD) dilatation, pancreatic atrophy, and
      peripancreatic tissue metastasis were evaluated. Images were cross-referenced to
      surgical and pathologic findings. RESULTS: Masses were distributed throughout the
      pancreas (head, n=6; body, n=1; and tail, n=5). The tumor size ranged from 2.4 to
      5.5 cm with an average size of 3.7 cm. Eight (66.7%) masses were ill defined, and
      seven (58.3%) were partially exophytic. Twelve (100%) masses showed heterogeneous
      and poorly enhanced areas. The lesions showed weak (n=5), moderate (n=5), or
      intense (n=2) progressive enhancement. The diameter of MPD in six patients ranged
      from 3.0 to 5.0 mm with an average of 3.7 mm. Pancreatic atrophy was not found.
      In 10 patients (83.3%), masses invaded the peripancreatic tissues. Two patients
      had metastatic liver disease at presentation. CONCLUSION: PASC typically
      presented as an ill-defined, hypovascular mass with a poorly enhanced area,
      exophytic tendency, and peripancreatic tissue invasion. Lack of pancreatic
      atrophy and mild MPD dilatation were also distinct from common duct pancreatic
      adenocarcinoma.

PMID- 24035525
TI  - Is ultrasound useful in detection and follow-up of gastric foreign bodies in
      children?
AB  - OBJECTIVE: The objective was to show potential value of ultrasound in detection
      and follow-up of gastric foreign bodies. MATERIAL AND METHODS: Medical records of
      18 children with gastric foreign bodies were evaluated retrospectively. RESULTS:
      The following gastric foreign bodies were identified: eight coins, five button
      batteries, domino, lollipop stick, hairclip, screw nut, and small plastic
      cylinders. All were confirmed by ultrasound. The batteries, domino, and two coins
      were removed endoscopically, the screw nut was removed surgically, while the rest
      were recovered in the stool. CONCLUSIONS: Ultrasound examination of water-filled
      stomach can be useful in diagnostic workup of gastric foreign bodies in children,
      especially radiolucent ones.

PMID- 24035526
TI  - Intraoperative contrast-enhanced ultrasound in traumatic brain surgery.
AB  - OBJECTIVE: The objective was to assess intraoperative contrast-enhanced
      ultrasound (CEUS) in traumatic brain surgery. METHODS: We prospectively performed
      intraoperative conventional ultrasound (IOUS) and CEUS in 32 patients who
      underwent emergency surgery for the treatment of traumatic brain injury (TBI).
      Sonographic appearance including echogenicity, border, and size of the traumatic
      lesion and adjacent brain tissue on CEUS were compared with those on IOUS using
      surgical results as the gold standard. The differences in the size and contrast
      enhancement parameters of the lesions between IOUS and CEUS were analyzed with a
      paired t test. RESULTS: The accuracy of CEUS in assessing TBI was 100%, whereas
      IOUS was 51%. The absolute peak intensity (API) varied depending on the severity
      of brain injury. Lower API was observed in severely damaged brain tissue, whereas
      high API was seen in normal brain tissue or the brain tissue with mild injury.
      The border of the trauma lesion was more clearly defined on CEUS when compared to
      IOUS. The size of the lesions measured on CEUS was significantly larger than that
      on IOUS (P<.01). Importantly, small vessels supplying blood to the tissue in
      traumatic lesions, as an indication of possible brain vitality, were optimized on
      CEUS during the surgery. Based on the parameter of time intensity curve and
      appearances of the lesions on CEUS, the severity of lesions was reclassified and
      surgical intervention was redesigned in 21 (21/32, 66%) cases. CONCLUSION:
      Intraoperative CEUS improves accuracy in classification of traumatic brain
      injury, which helps neurosurgeons to effectively remove hematoma, preserve normal
      brain tissue, and prevent damaging the vessels during surgical intervention.

PMID- 24035527
TI  - [Nodular fasciitis: case report and review of the literature].
AB  - Among soft tissue tumors, nodular fasciitis is a relatively common tumor process,
      which occurs in the 30 first years of life. Nodular fasciitis is a benign tumor
      with a rapid proliferation of myofibroblastic cells, which develops at the
      expense of a muscular fascia in the subcutaneous tissue. Usual localizations are
      the trunk and upper limbs. Difficulty of diagnosis consists in the need to
      eliminate many differential diagnoses especially malignant tumor processes. From
      a clinical point of view, the rapid development of nodular fasciitis (from some
      days to some weeks) must fear a malignant process. This benign lesion, which does
      not recur (even if incomplete resection), may regress spontaneously. We report
      such a tumor located at the cubital fossa confirmed by a pathological
      examination. 

PMID- 24035528
TI  - Results of a laparoscopic approach for the treatment of acute small bowel
      obstruction due to adhesions and internal hernias.
AB  - INTRODUCTION: Laparotomy is the standard approach for the surgical treatment of
      acute small bowel obstruction (ASBO). PATIENTS AND METHODS: From February 2007 to
      May 2012 we prospectively recorded all patients operated by laparoscopy in our
      hospital because of ASBO due to adhesions (27 cases) and/or internal hernia (6
      cases). A preoperative abdominal CT was performed in all cases. Patients
      suffering from peritonitis and/or sepsis were excluded from the laparoscopic
      approach. It was decided to convert to laparotomy if intestinal resection was
      required. RESULTS: The mean age of the 33 patients who underwent surgery was 61.1
      +/- 17.6 years. 64% had previous history of abdominal surgery. 72% of the cases
      were operated by surgeons highly skilled in laparoscopy. Conversion rate was 21%.
      Operative time and postoperative length of stay were 83 +/- 44 min. and 7.8 +/-
      11.2 days, respectively. Operative time (72 +/- 30 vs 123 +/- 63 min.), tolerance
      to oral intake (1.8 +/- 0.9 vs 5.7 +/- 3.3 days) and length of postoperative stay
      (4.7 +/- 2.5 vs 19.4 +/- 21 days) were significantly lower in the laparoscopy
      group compared with the conversion group, although converted patients had greater
      clinical severity (2 bowel resections). There were two severe complications
      (Clavien-Dindo III and V) in the conversion group. CONCLUSIONS: In selected cases
      of ASBO caused by adhesions and internal hernias and when performed by surgeons
      highly skilled in laparoscopy, a laparoscopic approach has a high probability of
      success (low conversion rate, short hospital length of stay and low morbidity);
      its use would be fully justified in these cases.

PMID- 24035529
TI  - [Pancreatoduodenectomy with reconstruction of an aberrant right hepatic artery].

PMID- 24035530
TI  - Behavioral abnormalities in progressive supranuclear palsy.
AB  - Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder in
      which, classically, patients present with postural instability and falls,
      parkinsonism, and slowing of vertical saccades. PSP patients typically have
      deficits in cognitive functioning, difficulties with most daily activities, and
      present with notable behavioral disturbances-particularly apathy, impulsivity,
      and irritability. Using data from 154 patients meeting criteria for clinically
      probable PSP, domain and total scores of the Neuropsychiatric Inventory were
      examined and compared to demographics, disease severity, cognition, and motor
      features. Behavioral abnormalities were common in this cohort of PSP patients,
      with more than half experiencing apathy, depression, and sleeping problems, and
      approximately one third displaying agitation, irritability, disinhibition, and
      eating problems. Few clinical correlates of neuropsychiatric symptoms were
      observed in this cohort. Given the prevalence of neuropsychiatric symptoms in
      PSP, these patients are expected to be frequently seen by psychiatrists and other
      mental health professionals for symptom management and increased quality of life.
      Clinical trials are clearly needed to address the neuropsychiatric morbidity in
      these patients. 

PMID- 24035531
TI  - Prediction of late distant recurrence in patients with oestrogen-receptor
      positive breast cancer: a prospective comparison of the breast-cancer index (BCI)
      assay, 21-gene recurrence score, and IHC4 in the TransATAC study population.
AB  - BACKGROUND: Biomarkers to improve the risk-benefit of extended adjuvant endocrine
      therapy for late recurrence in patients with oestrogen-receptor-positive breast
      cancer would be clinically valuable. We compared the prognostic ability of the
      breast-cancer index (BCI) assay, 21-gene recurrence score (Oncotype DX), and an
      immunohistochemical prognostic model (IHC4) for both early and late recurrence in
      patients with oestrogen-receptor-positive, node-negative (N0) disease who took
      part in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) clinical trial.
      METHODS: In this prospective comparison study, we obtained archival tumour blocks
      from the TransATAC tissue bank from all postmenopausal patients with oestrogen
      receptor-positive breast cancer from whom the 21-gene recurrence score and IHC4
      values had already been derived. We did BCI analysis in matched samples with
      sufficient residual RNA using two BCI models-cubic (BCI-C) and linear (BCI-L)
      using previously validated cutoffs. We assessed prognostic ability of BCI for
      distant recurrence over 10 years (the primary endpoint) and compared it with that
      of the 21-gene recurrence score and IHC4. We also tested the ability of the
      assays to predict early (0-5 years) and late (5-10 years) distant recurrence. To
      assess the ability of the biomarkers to predict recurrence beyond standard
      clinicopathological variables, we calculated the change in the likelihood-ratio
      chi(2) (LR-Deltachi(2)) from Cox proportional hazards models. FINDINGS: Suitable
      tissue was available from 665 patients with oestrogen-receptor-positive, N0
      breast cancer for BCI analysis. The primary analysis showed significant
      differences in risk of distant recurrence over 10 years in the categorical BCI-C
      risk groups (p<0.0001) with 6.8% (95% CI 4.4-10.0) of patients in the low-risk
      group, 17.3% (12.0-24.7) in the intermediate group, and 22.2% (15.3-31.5) in the
      high-risk group having distant recurrence. The secondary analysis showed that BCI
      L was a much stronger predictor for overall (0-10 year) distant recurrence
      compared with BCI-C (interquartile HR 2.30 [95% CI 1.62-3.27]; LR
      Deltachi(2)=22.69; p<0.0001). When compared with BCI-L, the 21-gene recurrence
      score was less predictive (HR 1.48 [95% CI 1.22-1.78]; LR-Deltachi(2)=13.68;
      p=0.0002) and IHC4 was similar (HR 1.69 [95% CI 1.51-2.56]; LR-Deltachi(2)=22.83;
      p<0.0001). All further analyses were done with the BCI-L model. In a
      multivariable analysis, all assays had significant prognostic ability for early
      distant recurrence (BCI-L HR 2.77 [95% CI 1.63-4.70], LR-Deltachi(2)=15.42,
      p<0.0001; 21-gene recurrence score HR 1.80 [1.42-2.29], LR-Deltachi(2)=18.48,
      p<0.0001; IHC4 HR 2.90 [2.01-4.18], LR-Deltachi(2)=29.14, p<0.0001); however,
      only BCI-L was significant for late distant recurrence (BCI-L HR 1.95 [95% CI
      1.22-3.14], LR-Deltachi(2)=7.97, p=0.0048; 21-gene recurrence score HR 1.13 [0.82
      1.56], LR-Deltachi(2)=0.48, p=0.47; IHC4 HR 1.30 [0.88-1.94], LR
      Deltachi(2)=1.59, p=0.20). INTERPRETATION: BCI-L was the only significant
      prognostic test for risk of both early and late distant recurrence and identified
      two risk populations for each timeframe. It could help to identify patients at
      high risk for late distant recurrence who might benefit from extended endocrine
      or other therapy. FUNDING: Avon Foundation, National Institutes of Health, Breast
      Cancer Foundation, US Department of Defense Breast Cancer Research Program, Susan
      G Komen for the Cure, Breakthrough Breast Cancer through the Mary-Jean Mitchell
      Green Foundation, AstraZeneca, Cancer Research UK, and the National Institute for
      Health Research Biomedical Research Centre at the Royal Marsden (London, UK).

PMID- 24035533
TI  - Multigene assays for late recurrence of breast cancer.

PMID- 24035532
TI  - Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review
      and network meta-analysis.
AB  - BACKGROUND: Major adjuvant treatments for pancreatic adenocarcinoma include
      fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil
      or gemcitabine. Since the optimum regimen remains inconclusive, we aimed to
      compare these treatments in terms of overall survival after tumour resection and
      in terms of grade 3-4 toxic effects with a systematic review and random-effects
      Bayesian network meta-analysis. METHODS: We searched PubMed, trial registries,
      and related reviews and abstracts for randomised controlled trials comparing the
      above five treatments with each other or observation alone before April 30, 2013.
      We estimated relative hazard ratios (HRs) for death and relative odds ratios
      (ORs) for toxic effects among different therapies by combining HRs for death and
      survival durations and ORs for toxic effects of included trials. We assessed the
      effects of prognostic factors on survival benefits of adjuvant therapies with
      meta-regression. FINDINGS: Ten eligible articles reporting nine trials were
      included. Compared with observation, the HRs for death were 0.62 (95% credible
      interval 0.42-0.88) for fluorouracil, 0.68 (0.44-1.07) for gemcitabine, 0.91
      (0.55-1.46) for chemoradiation, 0.54 (0.15-1.80) for chemoradiation plus
      fluorouracil, and 0.44 (0.10-1.81) for chemoradiation plus gemcitabine. The
      proportion of patients with positive lymph nodes was inversely associated with
      the survival benefit of adjuvant treatments. After adjustment for this factor,
      fluorouracil (HR 0.65, 0.49-0.84) and gemcitabine (0.59, 0.41-0.83) improved
      survival compared with observation, whereas chemoradiation resulted in worse
      survival than fluorouracil (1.69, 1.12-2.54) or gemcitabine (1.86, 1.04-3.23).
      Chemoradiation plus gemcitabine was ranked the most toxic, with significantly
      higher haematological toxic effects than second-ranked chemoradiation plus
      fluorouracil (OR 13.33, 1.01-169.36). INTERPRETATION: Chemotherapy with
      fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic
      adenocarcinoma and reduces mortality after surgery by about a third.
      Chemoradiation plus chemotherapy is less effective in prolonging survival and is
      more toxic than chemotherapy. FUNDING: None.

PMID- 24035534
TI  - Bayesian analysis unravels pancreas-cancer adjuvant therapy.

PMID- 24035535
TI  - Cannabis cue-induced brain activation correlates with drug craving in limbic and
      visual salience regions: preliminary results.
AB  - Craving is a major motivator underlying drug use and relapse but the neural
      correlates of cannabis craving are not well understood. This study sought to
      determine whether visual cannabis cues increase cannabis craving and whether cue
      induced craving is associated with regional brain activation in cannabis
      dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent
      adult volunteers while they viewed cannabis cues during a functional MRI (fMRI)
      scan. The Marijuana Craving Questionnaire was administered immediately before and
      after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level
      dependent (BOLD) signal intensity was determined in regions activated by cannabis
      cues to examine the relationship of regional brain activation to cannabis
      craving. Craving scores increased significantly following exposure to visual
      cannabis cues. Visual cues activated multiple brain regions, including inferior
      orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus,
      hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving
      scores at baseline and at the end of all three runs were significantly correlated
      with brain activation during the first fMRI run only, in the limbic system
      (including amygdala and hippocampus) and paralimbic system (superior temporal
      pole), and visual regions (occipital cortex). Cannabis cues increased craving in
      cannabis-dependent individuals and this increase was associated with activation
      in the limbic, paralimbic, and visual systems during the first fMRI run, but not
      subsequent fMRI runs. These results suggest that these regions may mediate
      visually cued aspects of drug craving. This study provides preliminary evidence
      for the neural basis of cue-induced cannabis craving and suggests possible neural
      targets for interventions targeted at treating cannabis dependence. 

PMID- 24035536
TI  - [Prolonged therapeutic hypothermia after pericardial effusion drain surgery].
AB  - Therapeutic hypothermia is an effective treatment for neurological protection
      after out-of-hospital cardiac arrest, and may also be beneficial for in-hospital
      cardiac arrest. Its use is limited in post-surgical patients due to the risk of
      specific complications, particularly bleeding. There are significant differences
      among previous publications regarding the time to reach the target temperature
      and the duration of therapy, so the optimal strategy is not yet established. We
      present the case of a patient who suffered a perioperative cardiac arrest related
      to a pericardial tamponade, and who underwent therapeutic hypothermia for 48h. 

PMID- 24035537
TI  - [Late spinal epidural abscess after epidural anesthesia].

PMID- 24035538
TI  - [A full-term pregnant woman with non-compaction cardiomyopathy].
AB  - Non-compaction cardiomyopathy, a genetic primary cardiomyopathy, is being
      increasingly diagnosed. Pregnant women with non-compaction cardiomyopathy are
      more susceptible to complications, such as heart failure, arrhythmias and embolic
      events. This paper reports the case of a pregnant woman with non-compaction
      cardiomyopathy under treatment and asymptomatic, who received epidural analgesia
      during labor and delivery. The clinical course is described and a brief review is
      presented. 

PMID- 24035539
TI  - Total intravenous anesthesia for aortic aneurysm replacement surgery in a patient
      with limb-girdle dystrophy.
AB  - We report the anesthetic management with total intravenous anesthesia of a 61
      year-old male diagnosed with limb-girdle muscular dystrophy admitted for
      replacement of ascending aorta due to an aortic aneurysm. Limb-girdle muscular
      dystrophy belongs to a genetically heterogeneous group of muscular dystrophies
      involving shoulder and hip girdles. Although the risk of malignant hyperthermia
      does not seem to be increased in these patients compared with the general
      population, the exposure to inhaled anesthetics and succinylcholine should
      probably be avoided because these patients have a predisposition to hyperkalemia
      and rhabdomyolysis. We chose to use total intravenous anesthesia with propofol,
      remifentanil and muscle relaxants to reduce oxygen consumption, and later to
      reduce the doses of propofol and remifentanil. The combination of a carefully
      planned anesthetic strategy, anesthetic depth, and neuromuscular blockade
      monitoring is explained. 

PMID- 24035540
TI  - [Incidental pancreatic paraganglioma].

PMID- 24035541
TI  - Genetic and neural modularity underlie the evolution of schooling behavior in
      threespine sticklebacks.
AB  - Although descriptions of striking diversity in animal behavior are plentiful,
      little is known about the mechanisms by which behaviors change and evolve between
      groups. To fully understand behavioral evolution, it will be necessary to
      identify the genetic mechanisms that mediate behavioral change in a natural
      context. Genetic analysis of behavior can also reveal associations between
      behavior and morphological or neural phenotypes, providing insight into the
      proximate mechanisms that control behavior. Relatively few studies to date have
      successfully identified genes or genomic regions that contribute to behavioral
      variation among natural populations or species, particularly in vertebrates.
      Here, we apply genetic approaches to dissect a complex social behavior that has
      long fascinated biologists, schooling behavior. We performed quantitative trait
      locus (QTL) analysis of schooling in an F2 intercross between strongly schooling
      marine and weakly schooling benthic sticklebacks (Gasterosteus aculeatus) and
      found that distinct genetic modules control different aspects of schooling
      behavior. Two key components of the behavior, tendency to school and body
      position when schooling, are uncorrelated in hybrids and map to different genomic
      regions. Our results further point to a genetic link between one behavioral
      component, schooling position, and variation in the neurosensory lateral line.

PMID- 24035543
TI  - Rates of phenotypic and genomic evolution during the Cambrian explosion.
AB  - The near-simultaneous appearance of most modern animal body plans (phyla) ~530
      million years ago during the Cambrian explosion is strong evidence for a brief
      interval of rapid phenotypic and genetic innovation, yet the exact speed and
      nature of this grand adaptive radiation remain debated. Crucially, rates of
      morphological evolution in the past (i.e., in ancestral lineages) can be inferred
      from phenotypic differences among living organisms-just as molecular evolutionary
      rates in ancestral lineages can be inferred from genetic divergences. We here
      employed Bayesian and maximum likelihood phylogenetic clock methods on an
      extensive anatomical and genomic data set for arthropods, the most diverse phylum
      in the Cambrian and today. Assuming an Ediacaran origin for arthropods,
      phenotypic evolution was ~4 times faster, and molecular evolution ~5.5 times
      faster, during the Cambrian explosion compared to all subsequent parts of the
      Phanerozoic. These rapid evolutionary rates are robust to assumptions about the
      precise age of arthropods. Surprisingly, these fast early rates do not change
      substantially even if the radiation of arthropods is compressed entirely into the
      Cambrian (~542 mega-annum [Ma]) or telescoped into the Cryogenian (~650 Ma). The
      fastest inferred rates are still consistent with evolution by natural selection
      and with data from living organisms, potentially resolving "Darwin's dilemma."
      However, evolution during the Cambrian explosion was unusual (compared to the
      subsequent Phanerozoic) in that fast rates were present across many lineages.

PMID- 24035542
TI  - Fission yeast does not age under favorable conditions, but does so after stress.
AB  - BACKGROUND: Many unicellular organisms age: as time passes, they divide more
      slowly and ultimately die. In budding yeast, asymmetric segregation of cellular
      damage results in aging mother cells and rejuvenated daughters. We hypothesize
      that the organisms in which this asymmetry is lacking, or can be modulated, may
      not undergo aging. RESULTS: We performed a complete pedigree analysis of
      microcolonies of the fission yeast Schizosaccharomyces pombe growing from a
      single cell. When cells were grown under favorable conditions, none of the
      lineages exhibited aging, which is defined as a consecutive increase in division
      time and increased death probability. Under favorable conditions, few cells died,
      and their death was random and sudden rather than following a gradual increase in
      division time. Cell death correlated with the inheritance of Hsp104-associated
      protein aggregates. After stress, the cells that inherited large aggregates aged,
      showing a consecutive increase in division time and an increased death
      probability. Their sisters, who inherited little or no aggregates, did not age.
      CONCLUSIONS: We conclude that S. pombe does not age under favorable growth
      conditions, but does so under stress. This transition appears to be passive
      rather than active and results from the formation of a single large aggregate,
      which segregates asymmetrically at the subsequent cell division. We argue that
      this damage-induced asymmetric segregation has evolved to sacrifice some cells so
      that others may survive unscathed after severe environmental stresses.

PMID- 24035544
TI  - Cytokinins control endocycle onset by promoting the expression of an APC/C
      activator in Arabidopsis roots.
AB  - Plant roots respond to various internal and external signals and adjust
      themselves to changes of environmental conditions. In the root meristem, stem
      cells produce daughter cells that continue to divide several times. When these
      latter cells reach the transition zone, they stop dividing and enter the
      endocycle, a modified cell cycle in which DNA replication is repeated without
      mitosis or cytokinesis. The resultant DNA polyploidization, named
      endoreduplication, is usually associated with an increase of nuclear and cell
      volume and with cell differentiation. At the transition zone, cytokinin signaling
      activates two transcription factors, type-B ARABIDOPSIS RESPONSE REGULATOR 1
      (ARR1) and ARR12, and induces SHY2/IAA3, a member of the Aux/IAA family of auxin
      signaling repressors. This inhibits auxin signaling and reduces the expression of
      auxin efflux carriers, resulting in cell division arrest. Such counteracting
      actions of two hormones are assumed to determine meristem size. However, it
      remains unknown whether cytokinins additionally control meristem size through an
      auxin-independent pathway. Here we show that, in Arabidopsis, the cytokinin
      activated ARR2 directly upregulates the expression of CCS52A1, which encodes an
      activator of an E3 ubiquitin ligase, anaphase-promoting complex/cyclosome
      (APC/C), thereby promoting the onset of the endocycle and restricting meristem
      size. Our genetic data revealed that CCS52A1 function is independent of SHY2
      mediated control of auxin signaling, indicating that downregulation of auxin
      signaling and APC/C-mediated degradation of cell-cycle regulators cooperatively
      promote endocycle onset, and thus fine tune root growth.

PMID- 24035546
TI  - Developmental priming of stomatal sensitivity to abscisic acid by leaf
      microclimate.
AB  - Plant water loss and CO2 uptake are controlled by valve-like structures on the
      leaf surface known as stomata. Stomatal aperture is regulated by hormonal and
      environmental signals. We show here that stomatal sensitivity to the drought
      hormone abscisic acid (ABA) is acquired during leaf development by exposure to an
      increasingly dryer atmosphere in the rosette plant Arabidopsis. Young leaves,
      which develop in the center of the rosette, do not close in response to ABA. As
      the leaves increase in size, they are naturally exposed to increasingly dry air
      as a consequence of the spatial arrangement of the leaves, and this triggers the
      acquisition of ABA sensitivity. Interestingly, stomatal ABA sensitivity in young
      leaves is rapidly restored upon water stress. These findings shed new light on
      how plant architecture and stomatal physiology have coevolved to optimize carbon
      gain against water loss in stressing environments. 

PMID- 24035545
TI  - Loss of schooling behavior in cavefish through sight-dependent and sight
      independent mechanisms.
AB  - BACKGROUND: Surface populations of Astyanax mexicanus, living in rivers like
      their common ancestors, school, while several, independently derived cave
      populations of the same species have lost schooling behavior. RESULTS: We
      quantify schooling behavior in individual A. mexicanus and identify quantitative
      trait loci (QTL) for this trait. We find that the evolutionary modulation of
      schooling has both vision-dependent and -independent components. We also quantify
      differences in the lateral line and vision between cavefish and surface fish and
      relate these differences to the evolutionary loss of schooling behavior. We
      provide evidence that a monoamine neurotransmitter may have played a role in the
      evolution of schooling behavior. CONCLUSIONS: We find that vision is essential
      for schooling tendency in A. mexicanus, while the lateral line has a small effect
      on this behavior. Schooling behavior in A. mexicanus has evolved both through
      changes in sensory systems and through changes in genetic loci that likely act
      downstream of sensory inputs.

PMID- 24035547
TI  - Incidence and clinical course of Crohn's disease during the first year - results
      from the IBD Cohort of the Uppsala Region (ICURE) of Sweden 2005-2009.
AB  - BACKGROUND AND AIMS: As a part of the Swedish ICURE study where the
      epidemiological results of ulcerative colitis and microscopic colitis recently
      have been published, we hereby present the corresponding figures for Crohn's
      disease. METHODS: All patients diagnosed with Crohn's disease in Uppsala County
      (305,381 inhabitants) were prospectively registered during 2005-2006 and the same
      for all new patients with Crohn's disease in Uppsala Region (642,117 inhabitants)
      during 2007-2009. RESULTS: 264 patients with Crohn's disease were included. The
      mean annual incidence was 9.9/100,000/year (95% CI: 7.1-12.6). Incidence among
      children <17 years was 10.0/100,000/year (95% CI: 3.8-16.3). 51% of the patients
      had ileal involvement (L1: n=73, 28%. L2: n=129, 49%. L3: n=62, 23%, L4: n=47,
      18%) and 23% had a stricturing or penetrating disease (B1: n=204, 77%. B2: n=34,
      13%. B3: n=26, 10%. p: n=27, 10%). Intestinal resection rate during the first
      year was 12.5%. Patients with complicated disease had longer symptom duration
      before diagnosis compared to patients with non-complicated disease (median months
      12.0, IQR: 3.0-24.0 vs 4.0, IQR: 2.0-12.0, p=0.0032). Patients 40 years or older
      had an increased risk for surgery (HR: 2.03, 95% CI: 1.01-4.08, p=0.0457).
      CONCLUSIONS: The incidence of Crohn's disease in a region of Sweden is one of the
      highest reported in Europe. Long symptom duration precedes stricturing or
      penetrating behaviour. Old age is an independent risk factor for surgery.

PMID- 24035548
TI  - Echinococcus granulosus in Portugal: the first report of the G7 genotype in
      cattle.
AB  - Although cystic echinococcosis (CE) has been a recognized public health problem
      in Portugal, molecular data regarding the types and prevalence of infecting
      strains of its etiological agent (Echinococcus granulosus) are still scarce. Over
      the last years we have been evaluating the prevalence of CE in the country, and
      in this report we determined the parasite genotypes infecting sheep, goats,
      cattle and human in Portugal, based on 209 hydatid cysts recovered from liver
      (n=96), lung (n=95), pancreas (n=17) and kidney (n=1) samples obtained between
      2008 and 2011. Protoscoleces or germinal layers were collected from individual
      cysts, DNA was extracted, and a part of the mitochondrial DNA encoding the
      cytochrome c oxidase subunit 1 was amplified by PCR. Overall, the results confirm
      the overall dominance of the G1-G3 cluster of strains, which are particularly
      prevalent in southern Portugal in livestock ruminants. Unexpectedly, one parasite
      sequence with cattle origin was found to correspond to E. granulosus G7 genotype
      (also known as E. intermedius), here reported for the first time in bovine, in
      Portugal. 

PMID- 24035550
TI  - 64Cu-Labeled tetraiodothyroacetic acid-conjugated liposomes for PET imaging of
      tumor angiogenesis.
AB  - INTRODUCTION: We synthesized and evaluated (64)Cu-labeled tetraiodothyroacetic
      acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because
      tetrac inhibits angiogenesis via integrin alphaVbeta3. METHODS: Tetrac-PEG-DSPE
      and DOTA-PEG-DSPE were synthesized and formulated with other lipids into
      liposomes. The resulting tetrac/DOTA-liposomes were labeled with (64)Cu at 40 
      degrees C for 1 h and purified using a PD-10 column. (64)Cu-DOTA-liposomes were
      also prepared for comparison. Human aortic endothelial cell (HAEC) binding
      studies were performed by incubating the liposomes with the cells at 37  degrees
      C. MicroPET imaging followed by tissue distribution study was carried out using
      U87MG tumor-bearing mice injected with tetrac/(64)Cu-DOTA-liposomes or (64)Cu
      DOTA-liposomes. RESULTS: HAEC binding studies exhibited that tetrac/(64)Cu-DOTA
      liposomes were avidly taken up by the cells from 1.02 %ID at 1 h to 11.89 %ID at
      24 h, while (64)Cu-DOTA-liposomes had low uptake from 0.47 %ID at 1 h to 1.57 %ID
      at 24 h. MicroPET imaging of mice injected with tetrac/(64)Cu-DOTA-liposomes
      showed high radioactivity accumulation in the liver and spleen. ROI analysis of
      the tumor images revealed 1.93 +/- 0.12 %ID/g at 1 h and 2.70 +/- 0.36 %ID/g at
      22 h. In contrast, tumor ROI analysis of (64)Cu-DOTA-liposomes revealed 0.54 +/-
      0.08 %ID/g at 1 h and 0.52 +/- 0.09 %ID/g at 22 h. Tissue distribution studies
      confirmed that the tumor uptakes of tetrac/(64)Cu-DOTA-liposomes and (64)Cu-DOTA
      liposomes were 1.75 +/- 0.03 %ID/g and 0.36 +/- 0.01 %ID/g at 22 h, respectively.
      CONCLUSION: These results demonstrate that tetrac/(64)Cu-DOTA-liposomes have
      significantly enhanced tumor uptake compared to (64)Cu-DOTA-liposomes due to
      tetrac conjugation. Further studies are warranted to reduce the liver and spleen
      uptake of tetrac/(64)Cu-DOTA-liposomes.

PMID- 24035551
TI  - [Inadequate secretion of beta-human chorionic gonadotropin in lung cancer].
AB  - INTRODUCTION: The inadequate secretion of beta-human chorionic gonadotropin (beta
      HCG) during non-small cell lung cancer (NSCLC) is rare and quite ignored. The
      dosage of beta-HCG is probably not systematically realized in women who are in
      age of pregnancy and who need chemotherapy (CT) despite the descriptions of cases
      of prescription of CT against lung cancer in women who were pregnant. The
      incidence of NSCLC cancer is increasing and the risk to prescribe a CT in a woman
      who is pregnant is also increasing. CASES REPORTS: We describe the cases of two
      women and one man who had an augmentation of the beta-HCG plasmatic level before
      the prescription of CT against lung cancer. In women, the differential diagnostic
      between inadequate secretion of beta-HCG and pregnancy has been a problem.
      CONCLUSION: The inadequate secretion of beta-HCG during NSCLC is probably not so
      rare. The dosage of this hormone before each infusion of CT should be systematic
      to avoid the realization of CT during pregnancy. This raises the question of the
      method for differential diagnostic between pregnancy and inadequate secretion of
      beta-HCG in young women who suffer from NSCLC, especially when a small level of
      beta-HCG is measured.

PMID- 24035549
TI  - An improved preparation of [18F]FPBM: a potential serotonin transporter (SERT)
      imaging agent.
AB  - INTRODUCTION: In vivo positron emission tomography (PET) imaging of the serotonin
      transporter (SERT) is a valuable tool in drug development and in monitoring brain
      diseases with altered serotonergic function. We have developed a two-step
      labeling reaction for the preparation of the high serotonin affinity ligand
      [(18)F]FPBM ([(18)F]2-(2'-((dimethylamino)methyl)-4'-(3
      fluoropropoxy)phenylthio)benzenamine, 1). METHOD: To improve and automate the
      radiolabeling of [(18)F]FPBM, 1, an intermediate, [(18)F]3-fluoropropyltosylate,
      [(18)F]4, was prepared first, and then it was reacted with the phenol precursor
      (4-(2-aminophenylthio)-3-((dimethylamino)methyl)phenol, 3) to afford [(18)F]FPBM,
      1. To optimize the labeling, this O-alkylation reaction was evaluated under
      different temperatures, using different bases and varying amounts of precursor 3.
      The desired product was obtained after a solid phase extraction (SPE)
      purification. RESULTS: This two-step radiolabeling reaction successfully produced
      the desired [(18)F]FPBM, 1, with an excellent radiochemical purity (>95%, n = 8).
      Radiochemical yields were between 31% and 39% (decay corrected, total time of
      labeling: 70 min, n = 8). The SPE purification cannot completely remove pseudo
      carriers in the final dose of [(18)F]FPBM, 1. The concentrations of major pseudo
      carriers were measured by UV-HPLC (476-676, 68-95 and 50-71 MUg for precursor 3,
      O-hydroxypropyl and O-allyloxy derivatives, 5 and 6, respectively). To
      investigate the potential inhibition of SERT binding of these pseudo-carriers, we
      performed in vitro competition experiments evaluated by autoradiography. Known
      amounts of 'standard' FPBM, 1, of the pseudo-carriers, 5 and 6, were added to the
      HPLC-purified [(18)F]1 dose. The inhibition of 'standard' FPBM, 1, binding to the
      SERT binding sites, using monkey brain sections, were measured (EC50=13, 46, 7.1
      and 8.3 nM, respectively for 1, precursor 3, O-hydroxypropyl and O-allyloxy
      derivative of 3). CONCLUSION: An improved radiolabeling method by a SPE
      purification for preparation of [(18)F]FPBM, 1, was developed. The results
      suggest that it is feasible to use this labeling method to prepare [(18)F]FPBM,
      1, without affecting in vivo SERT binding.

PMID- 24035552
TI  - Burden of disease due to cancer in a Southern Brazilian state.
AB  - BACKGROUND: Despite the considerable epidemiological relevance of cancer in
      developing countries, there are very few studies of the burden related to cancer.
      The aim of this study was to present and discuss data from a burden-of-cancer
      study performed in a Southern Brazilian state. METHODS: An epidemiological study
      of ecological design was performed to calculate the disability-adjusted life year
      (DALY) index. The study was based on records of individuals admitted and treated
      for cancer in the Brazilian National Health System Hospitals, or individuals who
      had died of cancer while residing in the state of Santa Catarina in 2008.
      RESULTS: A total of 73,872.9 DALYs were estimated, which generated a rate of
      1220.5 DALYs/100,000 inhabitants. The highest DALYs were those for cancer of the
      trachea, bronchus and lung with 179.0/100,000 inhabitants, gastric cancer with
      101.7/100,000 inhabitants, and breast cancer with 99.7/100,000 inhabitants. The
      percentage contribution of the DALY component varied according to cancer type;
      however, mortality was the major component in all types. The highest rates were
      observed in 60-69-year-olds with 6071.3/100,000 inhabitants, in 70-79-year-olds
      with 5095.4/100,000 inhabitants, and in 45-59-year-olds with 3189.0 DALY/100,000
      inhabitants; 53.7% of DALYs occurred in males. CONCLUSIONS: The greatest burden
      of disease due to cancer in Santa Catarina was attributed to cancer of the
      trachea, bronchus and lung, followed by gastric and breast cancers. The mortality
      component was responsible for the greatest burden.

PMID- 24035553
TI  - In vivo confocal microscopy in clinical practice: comparison of bedside
      diagnostic accuracy of a trained physician and distant diagnosis of an expert
      reader.
AB  - BACKGROUND: Reflectance confocal microscopy (RCM) is an imaging tool that allows
      the visualization of cellular details without biopsy. To our knowledge, RCM
      sensitivity and specificity has not been studied in a telemedicine setting.
      OBJECTIVE: We sought to assess RCM diagnostic accuracy in a support
      teleconsultation setting. METHODS: Between June 2010 and September 2011, 340
      lesions were imaged using a confocal scanning microscope. The images were
      evaluated by 2 readers, one on site, and the other at a distance. RESULTS: A
      total of 334 cases were included. For each reader the sensitivity was greater
      than 90% and specificity for each reader was greater than 60%. Both readers had a
      combined sensitivity of 98.6% and 44% specificity. LIMITATIONS: RCM may be
      limited in the correct classification of epithelial tumors. CONCLUSIONS: RCM is a
      tool in the clinical diagnosis of skin lesions, providing a high diagnostic
      accuracy in teleconsultation use.

PMID- 24035554
TI  - Duration of efficacy increases with the repetition of botulinum toxin A
      injections in primary axillary hyperhidrosis: a study in 83 patients.
AB  - BACKGROUND: Intradermal injections of botulinum toxin are effective but
      transitory in primary axillary hyperhidrosis. These injections are repeated when
      the symptoms recur. The reported duration of efficacy is variable, from 2 to 24
      months, but it is unknown how the duration of efficacy changes when injections
      are repeated. OBJECTIVE: In this retrospective study, we aimed to evaluate
      changes in the duration of efficacy of botulinum toxin injections (Dysport,
      Ipsen, Boulogne-Billancourt, France) with the repetition of injections in
      patients with axillary hyperhidrosis. METHODS: From May 2001 to April 2012
      inclusive, 83 patients were treated with a dose of 125 U per underarm. We
      compared the duration of effect of the first and last toxin injections. RESULTS:
      The median duration of efficacy for the first injection was 5.5 months, whereas
      that for the last injection was 8.5 months. The difference between these 2
      durations is statistically significant (P = .0002). LIMITATIONS: Although
      retrospective and based on the declarative, this work is the first to our
      knowledge to highlight this benefit of treatment and to evaluate botulinum toxin
      over such a long period (11 years). CONCLUSION: There appears to be an increase
      in the duration of efficacy of botulinum toxin A injections with the repetition
      of injections in patients with primary axillary hyperhidrosis. The reasons for
      this effect may be linked to the mechanism of action of botulinum toxin, and may
      improve our understanding of its pharmacologic effects.

PMID- 24035555
TI  - Mortality risk factors and excess mortality in a cohort of cocaine users admitted
      to drug treatment in Spain.
AB  - We assessed mortality risk factors and excess mortality compared to the general
      population in two Spanish sub-cohorts of 8,825 cocaine and heroin users (CHUs)
      and 11,905 only cocaine users (OCUs) aged 15-49 admitted to drug treatment.
      Heroin use (among all cocaine users), no-regular employment and drug injection
      (among CHUs and OCUs), daily cocaine use and previous drug treatment (among CUs),
      and death before 2005 and >10 years of heroin use (among CHUs) were clearly
      associated with higher mortality in Cox regression. Excess mortality was assessed
      by the directly standardized mortality rate ratio, which was higher in CHUs
      (14.3; 95% CI: 12.6-16.2) than CUs (5.1; 95% CI: 4.3-6.0) and in women than men,
      especially among OCUs (8.6; 95% CI: 7.5-10.0 vs. 3.5; 95% CI: 3.3-3.8); it
      decreased with age among CHUs, but did not decrease overall during 1997-2008.
      OCUs excess mortality was considerable and showed no signs of decline, suggesting
      the need for improved treatment and prevention interventions.

PMID- 24035556
TI  - A randomized trial of Web-based videoconferencing for substance abuse counseling.
AB  - Web-based videoconferencing can improve access to substance abuse treatment by
      allowing patients to receive counseling services in their homes. This randomized
      clinical trial evaluates the feasibility and acceptability of Web-based
      videoconferencing in community opioid treatment program (OTP) participants.
      Participants that reported computer and Internet access (n=85) were randomly
      assigned to receive 12weeks of weekly individual counseling in-person or via
      eGetgoing, a Web-based videoconferencing platform. Fifty-nine of these
      participants completed the study (eGetgoing=24; in-person=35), with most study
      withdrawal occurring among eGetgoing participants. Participants exposed to the
      study conditions had similar rates of counseling attendance and drug-positive
      urinalysis results, and reported similar and strong ratings of treatment
      satisfaction and therapeutic alliance. These results support the feasibility and
      acceptability of Web-based counseling as a good method to extend access to
      individual substance abuse counseling when compared to in-person counseling for
      patients that are able to maintain a computer and Internet connection for
      reliable communication. 

PMID- 24035557
TI  - Tracking artemisinin resistance in Plasmodium falciparum.

PMID- 24035558
TI  - Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium
      falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies.
AB  - BACKGROUND: Artemisinin resistance in Plasmodium falciparum lengthens parasite
      clearance half-life during artemisinin monotherapy or artemisinin-based
      combination therapy. Absence of in-vitro and ex-vivo correlates of artemisinin
      resistance hinders study of this phenotype. We aimed to assess whether an in
      vitro ring-stage survival assay (RSA) can identify culture-adapted P falciparum
      isolates from patients with slow-clearing or fast-clearing infections, to
      investigate the stage-dependent susceptibility of parasites to dihydroartemisinin
      in the in-vitro RSA, and to assess whether an ex-vivo RSA can identify
      artemisinin-resistant P falciparum infections. METHODS: We culture-adapted
      parasites from patients with long and short parasite clearance half-lives from a
      study done in Pursat, Cambodia, in 2010 (registered with ClinicalTrials.gov,
      number NCT00341003) and used novel in-vitro survival assays to explore the stage
      dependent susceptibility of slow-clearing and fast-clearing parasites to
      dihydroartemisinin. In 2012, we implemented the RSA in prospective parasite
      clearance studies in Pursat, Preah Vihear, and Ratanakiri, Cambodia
      (NCT01736319), to measure the ex-vivo responses of parasites from patients with
      malaria. Continuous variables were compared with the Mann-Whitney U test.
      Correlations were analysed with the Spearman correlation test. FINDINGS: In-vitro
      survival rates of culture-adapted parasites from 13 slow-clearing and 13 fast
      clearing infections differed significantly when assays were done on 0-3 h ring
      stage parasites (10.88% vs 0.23%; p=0.007). Ex-vivo survival rates significantly
      correlated with in-vivo parasite clearance half-lives (n=30, r=0.74, 95% CI 0.50
      0.87; p<0.0001). INTERPRETATION: The in-vitro RSA of 0-3 h ring-stage parasites
      provides a platform for the molecular characterisation of artemisinin resistance.
      The ex-vivo RSA can be easily implemented where surveillance for artemisinin
      resistance is needed. FUNDING: Institut Pasteur du Cambodge and the Intramural
      Research Program, NIAID, NIH.

PMID- 24035560
TI  - Verbal memory impairment in healthy siblings of patients with schizophrenia.
AB  - Cognitive deficits have been recognized as a core feature of schizophrenia (SZ)
      and are present in most patients. Verbal memory (VM), working memory (WM), and
      executive function (EF) are domains commonly impaired in patients with SZ. These
      latter domains have been related to the genetic risk of the disorder
      characterizing as possible endophenotypes. In order to study neurocognitive
      endophenotypes in a Brazilian population with elevated genetic risks to develop
      SZ, we measured VM (Hopkins Verbal Learning Test Revised), WM (Letter-Number
      Sequencing and Digit Span) and EF (Stroop Test) in 90 subjects (45 unaffected
      siblings of patients with SZ and 45 matched healthy controls). No differences
      were found in EF and WM (Letter-Number Sequencing and Digit Span). However, in
      VM, siblings of patients performed worse than controls on the immediate recall
      and delayed recall. Our results suggest that VM impairment could be considered an
      endophenotype of SZ. 

PMID- 24035562
TI  - Further evidence for the association between the LSM1 gene and schizophrenia.

PMID- 24035563
TI  - Altered time course of unconscious response priming in schizophrenia patients.

PMID- 24035561
TI  - Proteoglycan abnormalities in olfactory epithelium tissue from subjects diagnosed
      with schizophrenia.
AB  - Emerging evidence points to proteoglycan abnormalities in the pathophysiology of
      schizophrenia (SZ). In particular, markedly abnormal expression of chondroitin
      sulfate proteoglycans (CSPGs), key components of the extracellular matrix, was
      observed in the medial temporal lobe. CSPG functions, including regulation of
      neuronal differentiation and migration, are highly relevant to the
      pathophysiology of SZ. CSPGs may exert similar functions in the olfactory
      epithelium (OE), a continuously regenerating neural tissue that shows cell and
      molecular abnormalities in SZ. We tested the hypothesis that CSPG expression in
      OE may be altered in SZ. CSPG-positive cells in postmortem OE from non
      psychiatric control (n=9) and SZ (n=10) subjects were counted using computer
      assisted light microscopy. 'Cytoplasmic' CSPG (c-CSPG) labeling was detected in
      sustentacular cells and some olfactory receptor neurons (c-CSPG+ORNs), while
      'pericellular' CSPG (p-CSPG) labeling was found in basal cells and some ORNs (p
      CSPG+ORNs). Dual labeling for CSPG and markers for mature and immature ORNs
      suggests that c-CSPG+ORNs correspond to mature ORNs, and p-CSPG+ORNs to immature
      ORNs. Previous studies in the same cohort demonstrated that densities of mature
      ORNs were unaltered (Arnold et al., 2001). In the present study, numerical
      densities of c-CSPG+ORNs were significantly decreased in SZ (p<0.025; 99.32%
      decrease), suggesting a reduction of CSPG expression in mature ORNs. Previous
      studies showed a striking increase in the ratios of immature neurons with respect
      to basal cells. In this study, we find that the ratio of p-CSPG+ORNs/CSPG+basal
      cells was significantly increased (p=0.03) in SZ, while numerical density changes
      of p-CSPG+ORNs (110.71% increase) or CSPG+basal cells (53.71% decrease), did not
      reach statistical significance. Together, these results indicate that CSPG
      abnormalities are present in the OE of SZ and specifically point to a reduction
      of CSPG expression in mature ORNs in SZ. Given the role CSPGs play in OE cell
      differentiation and axon guidance, we suggest that altered CSPG expression may
      contribute to ORN lineage dysregulation, and olfactory identification
      abnormalities, observed in SZ. 

PMID- 24035564
TI  - Lifestyle related risk factors in a multi-ethnic cohort of pregnant women:
      preliminary results from the Born in Bradford study.

PMID- 24035565
TI  - Effective management of exposure keratopathy developed in intensive care units:
      the impact of an evidence based eye care education programme.
AB  - OBJECTIVES: To assess the impact of eye care education on the incidence of
      corneal exposure in intensive care units (ICU). RESEARCH METHODOLOGY/DESIGN:
      Approximately 300 ICU personnel were educated about eye care to reduce the
      incidence of corneal exposure. The patients were divided into two groups: pre
      training (Group 1: Between February 1, 2011 and March 31, 2011 [2 months]) and
      post-training periods (Group 2: Between April 1, 2011 and April 1 2012 [1 year]).
      We compared the groups for keratopathy incidence to evaluate the efficacy of this
      education. RESULTS: The number of patients were 762 in Group 1 and 6196 in Group
      2 (p = 0.335). Medians of patients followed in pre training ICU and post training
      ICU for each month were found to be 476 (interquartile range, 433-539) and 515
      (interquartile range, 490-528). Exposure keratopathy was identified in 8 eyes of
      6 patients (3 males and 3 females) in pre training ICU with the mean age of 27.6
      +/- 31.8 years and 5 eyes of 3 patients (1 male and 2 females) in post training
      ICU with the mean age of 41.3 +/- 32.1 years. No significant difference was
      noticed between two groups in terms of the medians of patients followed in ICUs
      for each month (p=0.335). The time of hospitalisation in ICU when the patients
      were consulted for the first ocular assessment in pre training ICU and post
      training ICU were found to be 13 +/- 8.7 days and 8 +/- 1.7 days, respectively.
      After the training, the decrease in incidence of exposure keratopathy was found
      to be highly significant (p < 0.001). CONCLUSION: We observed a highly
      significant reduction in the incidence of corneal exposure, following the eye
      care education programme.

PMID- 24035566
TI  - A critical ethnographic look at paediatric intensive care nurses and the
      determinants of nurses' job satisfaction.
AB  - The aim of this study is to examine key features within the cultural context in a
      Canadian Paediatric Intensive Care Unit (PICU) environment as experienced by
      nurses and to identify what these influences are and how they shape nurses'
      intentions to remain at critically ill children's bedsides for the duration of
      their careers. This is a qualitative study which follows a critical ethnographic
      approach. Over 20 hours of observation and face-to-face semi-structured
      interviews were conducted. Approximately one third of the nursing population at
      the research site PICU were interviewed (N=31). Participants describe a complex
      process of becoming an expert PICU nurse that involved several stages. By the
      time participants became experts in this PICU they believed they had
      significantly narrowed the power imbalance that exists between nursing and
      medicine. This study illuminates the role both formal and informal education
      plays in breaking the power barrier for nurses in the PICU. This level of
      expertise and mutual respect between professions aids in retaining nurses in the
      PICU. The lack of autonomy and/or respect shown to nurses by administrators
      appears to be one of the major stressors in nurses' working lives and can lead to
      attrition from the PICU. Family Centred Care (FCC) is practiced in paediatrics
      and certainly accentuated in the PICU as there is usually only one patient
      assigned per nurse, who thus afforded the time to provide comprehensive care to
      both the child and the family. This is considered one of the satisfiers for
      nurses in the PICU and tends to encourage retention of nurses in the PICU.
      However, FCC was found to be an inadequate term to truly encompass the type of
      holistic care provided by nurses in the PICU.

PMID- 24035567
TI  - Biomechanical effects of a 2 suture-pass medial inter-implant mattress on
      transosseous-equivalent rotator cuff repair and considerations for a "technical
      efficiency ratio".
AB  - BACKGROUND: Rotator cuff repair involving fewer tendon suture passes without
      compromising biomechanical performance would represent a technical advancement.
      An inter-implant "medial pulley-mattress" transosseous-equivalent (MP-TOE) repair
      requiring fewer tendon suture-passes was hypothesized to provide equivalent
      biomechanical characteristics compared to the control. METHODS: In 6 human
      cadaveric shoulders, a transosseous-equivalent (TOE) repair (control) was
      performed utilizing 2 separate medial mattresses resulting in 4 tendon-bridging
      sutures. In 6 matched-pairs, 2 single-loaded anchors were used to create a medial
      inter-implant mattress construct (all sutures shuttled in 1 tendon pass per
      anchor)-after knot-tying, the same tendon-bridging pattern as the control was
      created. A materials testing machine cyclically loaded each repair from 10-180 N
      for 30 cycles; each repair subsequently underwent failure testing. Gap and strain
      were measured with a video digitizing system. A "technical efficiency ratio"
      (TER) was defined as: (#knots + #suture passes + #suture limbs)/#fixation points.
      RESULTS: Cyclic and failure testing demonstrated no significant differences
      between constructs. Gap formation at cycle 30 was 5.3 +/- 0.8 mm (TOE) and 5.0 +/
      0.3 mm (MP-TOE) (P = .62). Cycle 30 anterior strain values were -16.0 +/- 7.3%
      (TOE) and -15.8 +/- 6.6% (MP-TOE) (P = .99). Yield loads were 208.7 +/- 2.7 N
      (TOE) and 204.0 +/- 1.3 N (MP-TOE) (P = .17). Mode of failure demonstrated less
      tendon cut-out with the MP-TOE repair. The MP-TOE repair has a TER of 2.0 vs 2.5
      for the control. CONCLUSION: The MP-TOE repair requiring fewer tendon suture
      passes, yet creating an additional inter-implant mattress configuration, is
      biomechanically equivalent to the original TOE technique, and may limit failure
      with improved medial load-sharing capacity. A TER may help quantify technical
      ease and help standardize comparisons between repair techniques.

PMID- 24035568
TI  - Measurements of the ispilateral capitellum can reliably predict the diameter of
      the radial head.
AB  - BACKGROUND: There is no validated method to determine the correct diameter of a
      radial head implant when the radial head is too comminuted to function as a
      template or during revision surgery when the radial head has been previously
      excised. The purpose of this study was to determine if ipsilateral capitellar
      dimensions could be used to predict the diameter of the radial head; and hence to
      assist with implant selection. METHODS: Computer tomography scans of 50 normal
      elbows were used to generate 3D models. Measurements of the radial head included
      the maximum (Dmax) and minimum (Dmin) outer diameters and the maximum (Dishmax)
      and minimum (Dishmin) articular dish diameters. Measurements of the humerus
      included the width of the capitellum (CAPwidth), and the width from the lateral
      aspect of the capitellum to the lateral trochlear ridge (CAP-TROCHridge).
      Relationships were determined with Pearson bivariate coefficients. RESULTS: The
      mean radial head dimensions were Dmax = 24.7 +/- 2.3 mm, Dmin = 23.5 +/- 2.3 mm,
      Dishmax = 18.2 +/- 1.9 mm and Dishmin = 16.8 +/- 1.7 mm. The mean capitellar
      measurements were CAPwidth (18.4 +/- 1.4 mm) and CAP-TROCHridge (23.0 +/- 2.1
      mm). The most significant correlations were found between Dmax and CAP-TROCHridge
      (R = .90, P < .001) and Dmin and CAP-TROCHridge (R = .90, P < .001). DISCUSSION:
      Radiologic measurements of the capitellum are useful in the estimation of native
      radial head diameter. The CAP-TROCHridge measurement was very strongly correlated
      with both the maximum and minimum diameters of the radial head. This suggests
      that CAP-TROCHridge may be useful to accurately predict the native radial head
      diameter. These morphological relationships were plotted to produce an implant
      selection chart for radial head sizing applicable to any implant system. LEVEL OF
      EVIDENCE: Basic science, anatomy study, CT imaging.

PMID- 24035569
TI  - Evident cognitive impairments in seemingly recovered patients after midazolam
      based light sedation during diagnostic endoscopy.
AB  - BACKGROUND/PURPOSE: Midazolam is a widely used sedative agent during colonoscopy,
      with cognitive toxicity. However, the potential cognitive hazard of midazolam
      based light sedation has not been sufficiently examined. We aimed to examine the
      cognitive safety and vulnerability profile under midazolam light sedation, with a
      particular focus on individual variations. METHODS: We conducted a prospective
      case-controlled study in an academic hospital. In total, 30 patients undergoing
      sedative colonoscopy as part of a health check-up were recruited.
      Neuropsychological testing on the full cognitive spectrum was evaluated at 15
      minutes and 120 minutes after low-dose midazolam administration. The modified
      reliable change index (RCI) was used for intrapersonal comparisons and
      controlling for practice effects. RESULTS: Midazolam affected psychomotor speed
      (48%), memory (40%), learning (32%), working memory (17%), and sustained
      attention (11%), while sparing orientation and the fluency aspect of executive
      function at the acute stage. Residual memory (10%) and learning (10%) impairments
      at 2 hours after administration were evidenced in some patients. The three object
      recall and digit symbol coding tests can serve as useful screening tools.
      CONCLUSION: Midazolam-based light sedation induced selective cognitive
      impairments and prolonged cognitive impairments occurred in patients with
      advanced age. A longer observation time and further screening were recommended
      for patients due to their at risk state.

PMID- 24035570
TI  - Response to "Novel Middle East respiratory syndrome coronavirus".

PMID- 24035572
TI  - Time to choose the path for Chinese doctors.

PMID- 24035571
TI  - Sphingosine-1-phosphate stimulated connective tissue growth factor expression in
      human buccal fibroblasts: Inhibition by epigallocatechin-3-gallate.
AB  - BACKGROUND/PURPOSE: Connective tissue growth factor (CCN2) has been associated
      with the pathogenesis of various fibrotic diseases, including oral submucous
      fibrosis (OSF). The chemical constituents of areca nut along with the mechanical
      trauma cause OSF. The coarse fibers of areca nut injure the mucosa and hence
      sphingosine-1-phosphate (S1P) is released at the wounded sites. Recent studies
      have shown that S1P is involved in wound healing and the development of fibrosis.
      The aims of this study were to investigate the effects of S1P on CCN2 expression
      in human buccal fibroblasts (HBFs) and identify the potential targets for drug
      intervention or chemoprevention of OSF. METHODS: Western blot analyses were used
      to study the effects of S1P on CCN2 expression and its signaling pathways in HBFs
      and whether epigallocatechin-3-gallate (EGCG), the main and most significant
      polyphenol in green tea, could inhibit this pathway. RESULTS: S1P significantly
      enhanced CCN2 synthesis in HBFs. This effect can be inhibited by c-Jun NH2
      terminal kinase (JNK) inhibitor and extracellular signal-regulated kinase
      inhibitor but not by P38 mitogen-activated protein kinase inhibitor.
      Interestingly, EGCG completely blocked S1P-induced CCN2 expression via
      suppressing S1P-induced JNK phosphorylation. CONCLUSION: S1P released by
      repetitive mechanical trauma during AN chewing may contribute to the pathogenesis
      of OSF through upregulating CCN2 expression in HBFs. EGCG could be an adjuvant to
      the current offered therapy options or the prevention of OSF through suppression
      of JNK activation.

PMID- 24035573
TI  - Automatic detection of lift-off and touch-down of a pick-up walker using 3D
      kinematics.
AB  - Walking aids have been associated with falls and it is believed that incorrect
      use limits their usefulness. Measures are therefore needed that characterize
      their stable use and the classification of key events in walking aid movement is
      the first step in their development. This study presents an automated algorithm
      for detection of lift-off (LO) and touch-down (TD) events of a pick-up walker.
      For algorithm design and initial testing, a single user performed trials for
      which the four individual walker feet lifted off the ground and touched down
      again in various sequences, and for different amounts of frame loading
      (Dataset_1). For further validation, ten healthy young subjects walked with the
      pick-up walker on flat ground (Dataset_2a) and on a narrow beam (Dataset_2b), to
      challenge balance. One 88-year-old walking frame user was also assessed.
      Kinematic data were collected with a 3D optoelectronic camera system. The
      algorithm detected over 93% of events (Dataset_1), and 95% and 92% in Dataset_2a
      and b, respectively. Of the various LO/TD sequences, those associated with
      natural progression resulted in up to 100% correctly identified events. For the
      88-year-old walking frame user, 96% of LO events and 93% of TD events were
      detected, demonstrating the potential of the approach. 

PMID- 24035574
TI  - Vascular risk factors and cognitive disorders.
AB  - Delaying the onset of dementia by just a few years could have a major impact on
      the prevalence of the disease at the population level. Vascular risk factors are
      modifiable and may offer an important opportunity for preventive approaches.
      Several studies have shown that diabetes, hypertension, obesity, and smoking are
      associated with an increased risk of cognitive decline and dementia, but other
      groups have not observed such a relation. Positive associations were observed
      mainly in studies where risk factors were assessed in midlife, suggesting that
      age is an important modulator in the relation between vascular risk factors and
      cognition. The population attributable risk of dementia is particularly high for
      hypertension. Associations of vascular risk factors with cognitive decline and
      dementia are probably mediated largely by cerebrovascular disease, including both
      stroke and covert vascular brain injury, which can have additive or synergistic
      effects with coexisting neurodegenerative lesions. To date, randomized trials
      have not convincingly demonstrated that treating vascular risk factors is
      associated with a reduction in cognitive decline or dementia risk. Of eight
      randomized trials testing the effect of antihypertensive agents on dementia risk,
      only one was positive, and another in a subgroup of individuals with recurrent
      stroke. In most trials, cognition and dementia were secondary outcomes, follow-up
      was short and treatment was initiated at an older age. No effect on cognitive
      decline or dementia could be demonstrated for statins and intensive glycemic
      control. Future areas of investigation could include differential class effects
      of antihypertensive drugs on cognitive outcomes and identification of high risk
      individuals as target population for clinical trials initiated in midlife. 

PMID- 24035575
TI  - Frontotemporal lobar degeneration: diversity of FTLD lesions.
AB  - Frontotemporal lobar degeneration (FTLD) is a heterogeneous group including both
      sporadic and familial diseases, characterized by a macroscopic alteration. It may
      correspond to various cognitive syndromes: behavioral variant of frontotemporal
      dementia (bvFTD), progressive nonfluent aphasia, and semantic dementia. The
      neuropathologic classification is now based on identification of the protein that
      accumulates in neurons and glia: Tau, TAR DNA Binding Protein 43 (TDP-43), and
      FUsed in Sarcoma (FUS). The disorders in which the corresponding proteins
      accumulate have been named FTLD-Tau, FTLD-TDP, and FTLD-FUS. FTLD-Tau includes
      sporadic cases (e.g. Pick's disease) and Tau mutations. FTLD-TDP are subdivided
      within four types (A, B, C, D) according to the shape and distribution of TDP-43
      positive lesions within the associative frontal cortex. The FTLD-FUS group
      includes atypical FTLD with ubiquitinated lesions (FTLD-U), Neuronal Intermediate
      Filament Inclusion Disease (NIFID) and Basophilic Inclusion Body Disease (BIBD). 

PMID- 24035576
TI  - Innate immune cells in asthma.
AB  - Asthma is an inflammatory disease of the airways associated with a T helper (Th)2
      response. Such a response in the lungs requires complex interactions between
      innate cells and structural cells. Dendritic cells (DCs) are pivotal during
      sensitization to allergens but clearly require epithelium-derived signals to
      become activated. Epithelial cells also contribute to the activation and the
      survival of mast cells (MCs), basophils, and eosinophils and group 2 innate
      lymphoid cells (ILC2s). In turn, these innate cells can activate DCs to sustain
      Th2 immunity. Here, we review the role played by these different populations of
      immune cells in the pathogenesis of asthma and how they interact to orchestrate
      Th2 immunity. 

PMID- 24035577
TI  - Cost study of dermal substitutes and topical negative pressure in the surgical
      treatment of burns.
AB  - BACKGROUND: A recently performed randomised controlled trial investigated the
      clinical effectiveness of dermal substitutes (DS) and split skin grafts (SSG) in
      combination with topical negative pressure (TNP) in the surgical treatment of
      burn wounds. In the current study, medical and non-medical costs were
      investigated, to comprehensively assess the benefits of this new treatment.
      METHODS: The primary outcome was mean total costs of the four treatment
      strategies: SSG with or without DS, and with or without TNP. Costs were studied
      from a societal perspective. Findings were evaluated in light of the clinical
      effects on scar elasticity. RESULTS: Eighty-six patients were included. Twelve
      months post-operatively, highest elasticity was measured in scars treated with DS
      and TNP (p=0.027). The initial cost price of treatment with DS and TNP was ?2912
      compared to treatment with SSG alone ?1703 (p<0.001). However, mean total costs
      per patient did not differ significantly between groups (range ?29097-?43774).
      DISCUSSION: Costs of the interventional treatment contributed maximal 7% to the
      total costs and total costs varied widely within and between groups, but were not
      significantly different. Therefore, in the selection of the most optimal type of
      surgical intervention, cost considerations should not play an important role.

PMID- 24035578
TI  - Preputial flap as an adjunct to groin flap for the coverage of electrical burns
      in the hand.
AB  - High voltage electrical contact to hand result in injuries at multiple levels
      that may require more than a single flap for effective coverage. We present here
      a simple technique to utilise preputial flap as an adjunct to groin flap in cases
      where simultaneous coverage was required at more than one site in hands. In the
      past two years, 15 patients with unilateral involvement of hands due to
      electrical contact injury underwent this procedure. In addition to a comfortable
      position of the hand, stable and purposeful coverage at the wrist and various
      areas of hands was achieved in all the patients and none had flap failure. Minor
      complications related to penile erection were encountered that resulted in
      partial wound dehiscence that was managed with resuturing, pain relief and
      temporary suppression of erection. In our opinion, preputial flap is a good
      addition in our armamentarium to be used alongside groin flap for effective
      coverage of more than a single site requiring flap cover in electric injuries of
      the hand. 

PMID- 24035579
TI  - Transesophageal echocardiography in the management of burn patients.
AB  - A systematic review was conducted to assess the level of evidence for the use of
      transesophageal echocardiography (TEE) in the management of burn patients. We
      searched any article published before and including June 30, 2013. Our search
      yielded 118 total publications, 11 met the inclusion criteria of burn injury and
      TEE. Available studies published in any language were rated and included. At the
      present time, there are no available systematic reviews/meta-analyses published
      that met our search criteria. Only a small number of clinical trials, all with a
      limited number of patients were available. Therefore, a meta-analysis on outcome
      parameters was not performed. However, the major pathologic findings in burn
      patients were reduced left ventricular (LV) systolic and diastolic function,
      mitral valve vegetation, pulmonary hypertension, pericardial effusion, fluid
      overload, and right heart failure. The advantages of TEE include offering direct
      assessment of cardiac valve competency, myocardial contractility, and most
      importantly real time assessment of adequacy of hemodynamic resuscitation and
      preload in the acute phase of resuscitation, with minimal additional risk. TEE
      serves multiple diagnostic purposes and is being used to better understand the
      fluid status and cardiac physiology of the critically ill burn patient.
      Randomized controlled trials especially on fluid resuscitation and cardiac
      performance in acute burns are warranted to potentially further improve outcome. 

PMID- 24035580
TI  - Epidemiological analysis of burn patients in east Bulgaria.
AB  - OBJECTIVE: The purpose of the study was to identify the basic epidemiological
      characteristics of burn patients in East Bulgaria, as well as to analyze trends
      in burns in the region over the last decade. METHODS: Retrospective data of burn
      patients treated at Military Hospital-Varna, in the period January 2002-December
      2011, was reviewed and statistically interpreted in terms of patients and burn
      demographics; etiology; place of incidents; hospital stay and mortality. Trends
      were observed for the entire period and comparative analyses of patients' data
      were made between two periods: first - 2002-2006 and second 2007-2011. RESULTS: A
      total of 2627 burn patients, median age 41 years (IQR 9-61) were admitted to our
      burn unit. For the entire period the most affected age groups were <= 4 years
      (21.6%) and >= 65 years (21.1%). Hospitalized patients increased in the second
      period (n = 1701) compared to the first one (n = 926), while the size of total
      burn surface area decreased (first period - 9.8% vs. second period - 10.6%).
      Scald (51%) and flame (23.8%) were the most frequent aetiological agents for both
      periods. Work related burns reduced in the second period (9.4% vs. 4.9%), while
      home burns (90.6 vs. 95.1%) increased. Hospital stay declined from 17 days (2002
      2006) to 7 days (2007-2011), whereas mortality rate slightly increased (first
      period - 2.3% vs. second period - 3.6%). CONCLUSION: Burns remain a significant
      health problem in Bulgaria. The future preventive actions should take into
      account the observed changes in burn demographics and target the most vulnerable
      groups.

PMID- 24035581
TI  - What has changed in surgical treatment of severe aortic stenosis with the advent
      of percutaneous intervention?
AB  - INTRODUCTION AND OBJECTIVE: Transcatheter aortic valve implantation (TAVI) is an
      alternative therapeutic approach to patients not considered suitable for surgical
      aortic valve replacement (SAVR) due to their high operative risk. We sought to
      assess the impact of TAVI on the profile and operative results of patients with
      severe aortic stenosis undergoing SAVR. METHODS: A total of 214 patients were
      included, of whom 103 consecutive patients underwent isolated SAVR in 2005 and
      111 in 2009. Patients' demographic and operative data were collected
      retrospectively. Operative and one-year mortality and morbidity were analyzed.
      RESULTS: Patients' mean age was 70 years, and 56% were female. Following the
      introduction of a TAVI program, patients undergoing conventional surgery were
      older, with more comorbidities. Overall 30-day and one-year mortality were 2.8%
      and 7.0%, respectively. After the introduction of TAVI, the observed mortality
      rate for SAVR decreased, but not significantly (operative mortality: 3.9% before
      TAVI vs. 1.8% after TAVI, p = NS; one-year mortality: 10% vs. 4.5%, p = NS).
      Striking differences were observed in morbidity (operative morbidity: 23.3%
      before TAVI vs. 13.5% after TAVI, p = 0.047, and one-year morbidity: 20.4% vs.
      9.9%, p = 0.032). CONCLUSIONS: Since the introduction of a TAVI program at our
      center, the number of patients undergoing SAVR has increased, with a slight rise
      in surgical risk, but without worsening the final operative results. The
      implementation of a TAVI program has thus had a positive impact on the volume of
      procedures, patient selection and outcomes in SAVR.

PMID- 24035582
TI  - Incidence, aetiology, and control of sternal surgical site infections.
AB  - BACKGROUND: Since sternal surgical site infections (SSIs) can be life
      threatening, every effort should be made to reduce their rate of occurrence. AIM:
      To measure the rate of sternal SSIs after open heart surgery and to define the
      efficacy of infection control interventions in reducing this rate. METHODS:
      Surveillance of sternal SSIs was carried out prospectively for adult patients who
      underwent sternotomy between 2005 and 2012. Infection control interventions that
      were undertaken during the study period at different time intervals were
      prophylaxis with cefazolin or vancomycin, surveillance of sternal SSIs and
      feedback, preoperative nasal Staphylococcus aureus screening and decolonization
      with mupirocin, isolation of patients infected with or colonized by meticillin
      resistant S. aureus, appropriate management of perioperative blood glucose level
      and chlorhexidine/alcohol usage for skin antisepsis. FINDINGS: There were 479
      sternal SSIs in 18,460 patients during the study period (2.59%). The most
      frequent causes of sternal SSIs were coagulase-negative staphylococci (CoNS)
      (36%) and S. aureus (31%). Infection control interventions reduced the rate of
      sternal SSIs from 3.63% in 2005 to 1.65% in 2012 (P < 0.0001). CONCLUSION: Our
      study shows that the rate of sternal SSIs can be decreased with proper infection
      control interventions. However, the interventions that were undertaken were
      effective only in reducing the rate of sternal SSIs caused by S. aureus. It is
      time to find interventions to control sternal SSIs caused by CoNS, the pathogen
      responsible for most sternal SSIs in hospitals where S. aureus SSIs are
      successfully controlled.

PMID- 24035583
TI  - Treatment of a Salmonella-induced rapidly expanding aortic pseudoaneurysm
      involving the visceral arteries using the Cardiatis multilayer stent.
AB  - Treatment of infection-induced aortic aneurysms is among the greatest challenges
      nowadays of vascular surgery because the use of prosthetic material is considered
      unsuitable. The Cardiatis multilayer stent (Cardiatis, Isnes, Belgium) is a flow
      diverting bare stent with a proven efficacy in peripheral and visceral artery
      aneurysms. We present a unique case of a Salmonella serotype enteritidis-induced
      rapidly expanding aortic pseudoaneurysm with a penetrating ulcer that was treated
      with the Cardiatis multilayer stent. At 18 months of follow-up, the patient was
      in good clinical condition, with normalized C-reactive protein levels. Computed
      tomography angiography and 2-deoxy-2-[F18]-fluoro-d-glucose-positron-emission
      tomography/computed tomography showed a stable, mostly thrombosed aneurysm, with
      adequate perfusion of the side branches and no remaining signs of infection. 

PMID- 24035584
TI  - A review of the profile of endothelin axis in cancer and its management.
AB  - The endothelins and their associated receptors are important controllers of
      vascular growth, inflammation and vascular tone. In cancer, they have roles in
      the control of numerous factors in cancer development and progression, including
      angiogenesis, stromal reaction, epithelial mesenchymal transitions, apoptosis,
      invasion, metastases and drug resistance. Also, we consider current information
      on the role of this signalling system in cancer and examine the state of the
      current cell, animal and clinical trials utilizing endothelin targeted drugs for
      cancer management. Although targeting the endothelin axis in cell lines and
      xenografts show some promise in retarding cellular growth, results from limited
      clinical trials in prostatic cancer are less encouraging and did not offer
      significant survival benefit. The ability to target both cancer cells and
      vasculature via endothelin is an important consideration that necessitates the
      further refining of therapeutic strategies as we continue to explore the
      possibilities of the endothelin axis in cancer treatment. 

PMID- 24035585
TI  - Sequence characterization and immunogenicity of cystatins from the cattle tick
      Rhipicephalus (Boophilus) microplus.
AB  - Various classes of endopeptidases and their inhibitors facilitate blood feeding
      and digestion in ticks. Cystatins, a family of tight-binding and reversible
      inhibitors of cysteine endopeptidases, have recently been found in several tick
      tissues. Moreover, vaccine trials using tick cystatins have been found to induce
      protective immune responses against tick infestation. However, the mode of action
      of tick cystatins is still poorly understood, limiting the elucidation of their
      physiological role. Against this background, we have investigated sequence
      characteristics and immunogenic properties of 5 putative cystatins from
      Rhipicephalus (Boophilus) microplus from Brazil and Uruguay. The similarity of
      the deduced amino acid sequences among cystatins from the Brazilian tick strain
      was 27-42%, all of which had a secretory signal peptide. The cystatin motif
      (QxVxG), a glycine in the N-terminal region, and the PW motif in the second
      hairpin loop in the C-terminal region are highly conserved in all 5 cystatins
      identified in this study. Four cysteine residues in the C terminus characteristic
      of type 2 cystatins are also present. qRT-PCR revealed differential expression
      patterns among the 5 cystatins identified, as well as variation in mRNA
      transcripts present in egg, larva, gut, salivary glands, ovary, and fat body
      tissues. One R. microplus cystatin showed 97-100% amino acid similarity between
      Brazilian and Uruguayan isolates. Furthermore, by in silico analysis, antigenic
      amino acid regions from R. microplus cystatins showed high degrees of homology
      (54-92%) among Rhipicephalus spp. cystatins. Three Brazilian R. microplus
      cystatins were expressed in Escherichia coli, and immunogenicity of the
      recombinant proteins were determined by vaccinating mice. Western blotting using
      mice sera indicated cross-reactivity between the cystatins, suggesting shared
      epitopes. The present characterization of Rhipicephalus spp. cystatins represents
      an empirical approach in an effort to evaluate the physiological role of
      cystatins in a larger context of targeting them for use in future tick control
      strategies. 

PMID- 24035586
TI  - Detection and genetic characterization of tick-borne encephalitis virus (TBEV)
      derived from ticks removed from red foxes (Vulpes vulpes) and isolated from
      spleen samples of red deer (Cervus elaphus) in Croatia.
AB  - Tick-borne encephalitis (TBE) is a growing public health concern in central and
      northern European countries. Even though TBE is a notifiable disease in Croatia,
      there is a significant lack of information in regard to vector tick
      identification, distribution as well as TBE virus prevalence in ticks or animals.
      The aim of our study was to identify and to investigate the viral prevalence of
      TBE virus in ticks removed from red fox (Vulpes vulpes) carcasses hunted in
      endemic areas in northern Croatia and to gain a better insight in the role of
      wild ungulates, especially red deer (Cervus elaphus) in the maintenance of the
      TBE virus in the natural cycle. We identified 5 tick species (Ixodes ricinus,
      Ixodes hexagonus, Haemaphysalis punctata, Dermacentor reticulatus, Rhipicephalus
      sanguineus) removed from 40 red foxes. However, TBE virus was isolated only from
      adult I. ricinus and I. hexagonus ticks showing a viral prevalence (1.6%) similar
      to or higher than reported in endemic areas of other European countries.
      Furthermore, 2 positive spleen samples from 182 red deer (1.1%) were found.
      Croatian TBE virus isolates were genetically analyzed, and they were shown to be
      closely related, all belonging to the European TBE virus subgroup. However, on
      the basis of nucleotide and amino acid sequence analysis, 2 clusters were
      identified. Our results show that further investigation is needed to understand
      the clustering of isolates and to identify the most common TBE virus reservoir
      hosts in Croatia. Sentinel surveys based on wild animal species would give a
      better insight in defining TBE virus-endemic and possible risk areas in Croatia. 

PMID- 24035587
TI  - Angiogenesis and vascular functions in modulation of obesity, adipose metabolism,
      and insulin sensitivity.
AB  - White and brown adipose tissues are hypervascularized and the adipose vasculature
      displays phenotypic and functional plasticity to coordinate with metabolic
      demands of adipocytes. Blood vessels not only supply nutrients and oxygen to
      nourish adipocytes, they also serve as a cellular reservoir to provide adipose
      precursor and stem cells that control adipose tissue mass and function. Multiple
      signaling molecules modulate the complex interplay between the vascular system
      and the adipocytes. Understanding fundamental mechanisms by which angiogenesis
      and vasculatures modulate adipocyte functions may provide new therapeutic options
      for treatment of obesity and metabolic disorders by targeting the adipose
      vasculature. 

PMID- 24035589
TI  - Response to letter by Paul Effler and Heath Kelly to vaccine.

PMID- 24035590
TI  - A novel baculovirus vector shows efficient gene delivery of modified porcine
      reproductive and respiratory syndrome virus antigens and elicits specific immune
      response.
AB  - Porcine reproductive and respiratory syndrome (PRRS) is an economically
      devastating epizootic of porcine species. Current vaccines are inadequate to
      control the disease burden and outbreaks in the field. We report a novel
      baculovirus vaccine vector with White spot syndrome virus immediate early 1
      shuttle promoter, with strong activity in both insect cells and mammalian cells,
      for immunization against PRRSV. The insect cell cultured baculovirus vector
      produces PRRSV envelope glycoproteins ORF2a, ORF3, ORF4 and ORF5, which are
      similar to the antigens in the infectious PRRS virion, and these antigens are
      stably incorporated on the surface of the baculovirus. Further, the baculovirus
      vector efficiently transduces these antigens in cells of porcine origin, thereby
      simulating a live infection. The baculovirus vectored PRRSV antigens, upon
      inoculation in mice, elicits robust neutralizing antibodies against the infective
      PRRS virus. Further, the experiments indicate that hitherto under emphasized
      ORF2a and ORF4 are important target antigens for neutralizing PRRSV infectivity. 

PMID- 24035591
TI  - Neurodegenerative lesions: seeding and spreading.
AB  - Accumulation of specific proteins has replaced loss of specific populations of
      neurons in the definition of most neurodegenerative diseases. In some cases, the
      amino-acid sequence of the protein that accumulates is altered by a mutation in
      the gene that codes for it but most generally, the primary structure is normal.
      Much evidence from human neuropathology has been collected over the years
      indicating that the progression of the lesions in such neurodegenerative diseases
      as Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy
      follow the neuroanatomical connections. More recently, injection of aggregates of
      the specific proteins in the brain of experimental animals has been attempted in
      various experimental settings. Brain homogenates containing Abeta aggregates
      induce the early development of Abeta deposits in APP transgenic mice. Brain
      homogenates from various human tauopathies induce tau aggregates in transgenic
      mice expressing normal human tau. Finally, synthetic preformed fibrils of alpha
      synuclein initiate the development of alpha-synuclein accumulation resembling
      Parkinson's disease in wild-type mice. Experiments in cell cultures suggest that
      the protein has to be in some specific state of oligomerization or fibrillation
      to be endocytosed and transported by the neuron. These data suggest that the
      protein that accumulates in a specific disease is initially misfolded and that
      this misfolding contaminates normal protein in a prion-like manner - in some
      cases through the neuronal connections. 

PMID- 24035588
TI  - New opportunities: harnessing induced pluripotency for discovery in diabetes and
      metabolism.
AB  - The landmark discovery of induced pluripotent stem cells (iPSCs) by Shinya
      Yamanaka has transformed regenerative biology. Previously, insights into the
      pathogenesis of chronic human diseases have been hindered by the inaccessibility
      of patient samples. However, scientists are now able to convert patient
      fibroblasts into iPSCs and differentiate them into disease-relevant cell types.
      This ability opens new avenues for investigating disease pathogenesis and
      designing novel treatments. In this review, we highlight the uses of human iPSCs
      to uncover the underlying causes and pathological consequences of diabetes and
      metabolic syndromes, multifactorial diseases whose etiologies have been difficult
      to unravel using traditional methodologies. 

PMID- 24035593
TI  - Aphasia(s) in Alzheimer.
AB  - Language disorders of degenerative origin are frequently tied to Alzheimer
      disease (AD) the different variants of which can result in primary and secondary
      aphasia syndromes. More specifically, Alzheimer pathology can primarily erode
      frontal, temporal or parietal language cortices resulting in three genuine AD
      language variants which account for about 30% of primary degenerative aphasias.
      Likewise, it can spread from non-language to language cortices leading to
      secondary language disorders like in typical amnesic AD and in several atypical
      AD variants. This paper reviews the whole set of AD variants by characterising
      their impact on the neural language system and on linguistic functioning. It also
      provides cues for diagnostic strategies which are essential for linguistic,
      syndromic and nosological patient classification, for adequate clinical follow-up
      and for guiding language rehabilitation. Such diagnostic approaches, founded on
      detailed linguistic phenotyping while integrating anatomical and
      neuropathological findings, also represent a crucial issue for future drug trials
      targeting the physio-pathological processes in degenerative aphasias. 

PMID- 24035592
TI  - Semantic dementia: aspects of the early diagnosis.
AB  - Semantic dementia is a lobar atrophy syndrome, related to a degeneration of
      anterior temporal regions, and characterized by a very predominant impairment of
      semantic memory. Whereas the diagnosis is relatively easy to establish in the
      typical form and if the patient is seen early, the emergence of possible
      additional cognitive or psycho-behavioural disorders can lead to a misdiagnosis
      in favour of a frontotemporal dementia syndrome or even probable Alzheimer's
      disease. 

PMID- 24035594
TI  - Towards an earlier diagnosis of Alzheimer's disease presenting with visuospatial
      disorders (posterior cortical atrophy).
AB  - Progressive visual complaints related to visuospatial disorders, and less often
      to visuoperceptual disorders, may be the presenting and isolated manifestation of
      a focal degeneration in the posterior cortical areas, called posterior cortical
      atrophy (PCA). PCA is a clinical syndrome corresponding to a focal variant of
      Alzheimer's disease in 80% of cases. The predominant dysfunction in the
      occipitoparietal pathways results in predominant visuospatial disorders,
      manifesting primarily as dorsal simultanagnosia, alone or associated with other
      symptoms of Balint's syndrome. PCA is rare and affects young patients who are
      fully aware of their deficits. Diagnosis of PCA is often delayed, due to
      insidious onset and development of symptoms, and to poor awareness of the
      condition in the medical community. An earlier diagnosis requires both better
      knowledge of PCA among ophthalmologists and neurologists and better recognition
      of visual complaints, leading to simple bedside tasks that can tackle the
      syndrome. 

PMID- 24035595
TI  - FTY720 and cyclosporin protect ovarian tissue grafted into rabbits.
AB  - OBJECTIVE: To determine whether FTY720 combined with CsA has immunomodulatory
      effects on human ovarian tissue transplanted to the back muscle of rabbits for an
      8-week period. STUDY DESIGN: We selected rabbits as recipients of ovarian
      xenografts with and without treatment by CsA and FTY720. Ovarian fragments from
      twelve patients were cut into 2 mm * 2 mm, 1-2mm thick pieces and randomly
      distributed into four groups: Group 1 (FTY720 2 mg/kg/d+CsA 3 mg/kg/d), Group 2
      (FTY720 1 mg/kg/d+CsA 3mg/kg/d), Group 3 (FTY720 0.5 mg/kg/d+CsA 3mg/kg/d) and
      Group 4 for control (CsA 3 mg/kg/d). FTY720 was started three days before
      transplantation and was given daily after transplantation. CsA was administrated
      post-transplantation. All the animals were killed 8 weeks post- transplantation.
      Levels of serum estrogen (E2), interferon-gamma (IFN-gamma) and interleukin-4 (IL
      4) were detected by radioimmunoassay and ELISA. Anti-CD31 and anti-Ki-67
      antibodies were used to evaluate neo-vascularization in xenografts and
      proliferation activity of ovarian follicles. Peripheral CD4+/CD8+ T cells were
      analyzed by flow cytometry. RESULTS: Combined treatment with cyclosporin A and
      FTY720 improved graft survival and reduced peripheral CD4+ and CD8+ T cell counts
      compared to treatment with cyclosporin A alone. Neovascularization took place in
      the peripheral zone of the xenograft while granulosa cells, positively stained by
      Ki-67, were found in early-stage follicles and stromal cells in the combined
      treatment groups. CONCLUSION: FTY720 in combination with cyclosporin A maintains
      human ovarian xenografts in these rabbit models.

PMID- 24035597
TI  - [Acrodermatitis enteropathica-like disease in a full-term exclusively breast-fed
      infant].
AB  - Symptomatic zinc deficiency can occur in exclusively breast-fed infants. We
      report a case in a 5-month-old infant. CASE REPORT: A 5-month-old exclusively
      breast-fed boy presented with persistent erythema of breech since the age of 2
      months as well as perioral and acral erythematous scaly lesions. Laboratory
      investigations revealed low zinc levels in the infant's serum, the mother's
      plasma zinc level was normal, and breast milk zinc was low. Rapid healing
      occurred after oral zinc supplementation. DISCUSSION: Zinc deficiency in breast
      fed infants is a rare disease caused by a low level of zinc in the mother's milk.
      The clinical features resemble those of acrodermatitis enteropathica. Oral zinc
      supplementation is required until weaning.

PMID- 24035596
TI  - The complement anaphylatoxin receptors are not required for the development of
      experimental autoimmune uveitis.
AB  - To determine if complement anaphylatoxin-mediated inflammation contributes to the
      development and progression of experimental autoimmune uveitis (EAU), we induced
      disease in wild type and complement anaphylatoxin receptor-deficient mice (C3a
      receptor(-/-), C5a receptor(-/-) and C3aR(-/-)/C5aR(-/-)) and evaluated the eyes
      three weeks post-induction. No differences in disease severity or in disease
      incidence were seen between wild type controls and anaphylatoxin receptor
      deficient mice. Our data indicate that C3a and C5a-mediated functions are not
      critical to the development of EAU. 

PMID- 24035598
TI  - High frequencies of positive nickel/cobalt patch tests and high sweat nickel
      concentration in patients with intrinsic atopic dermatitis.
AB  - BACKGROUND: Atopic dermatitis (AD) is classified into extrinsic AD with high
      serum IgE levels and impaired barrier, and intrinsic AD with low serum IgE levels
      and unimpaired barrier. Intrinsic AD has a lower frequency of FLG mutations and a
      higher frequency of circulating Th1 cells, implying that non-protein antigens,
      represented by metals, may be an exacerbation factor in intrinsic AD. OBJECTIVE:
      To investigate metal allergy in intrinsic AD. METHODS: Enrolled in this study
      were 86 Japanese AD patients seen in three university hospitals, consisting of 55
      extrinsic and 31 intrinsic AD patients. Patch testing was performed, focusing on
      nickel, cobalt, and chrome, in parallel with other 14 metals. FLG mutations were
      analyzed in 49 patients (extrinsic, 29; intrinsic, 20). In 17 patients
      (extrinsic, 12; intrinsic, 5), sweat was collected from the forearms by exercise,
      and the concentration of nickel was fluorometrically measured. RESULTS: Nickel,
      cobalt, and chrome were the major positive metals. Intrinsic AD showed
      significantly higher percentages of positive reactions than extrinsic AD to
      nickel (intrinsic 41.9% vs extrinsic 16.4%, P=0.019) and cobalt (38.7% vs 10.9%,
      P=0.005). There was no significant difference between FLG mutation-bearing and
      non-bearing patients. The concentration of nickel was higher in the sweat of
      intrinsic AD than extrinsic AD patients (333.8 vs 89.4ng/g, P=0.0005) and
      inversely correlated with serum IgE levels. CONCLUSIONS: Nickel and cobalt
      allergy may be involved in intrinsic AD. Given that the metals are excreted
      through sweat, intrinsic AD might be exaggerated by highly metal-containing
      sweat.

PMID- 24035599
TI  - Adult-onset seizures in a patient with Down syndrome and portosystemic shunt.
AB  - OBJECTIVE: The prevalence of epilepsy in patients with Down syndrome (DS) is 5
      13%, which is higher than the prevalence in the general population. Transient
      hyperammonemia is often observed following seizure, but it typically resolves
      within a day. Here, we describe the case a 37-year-old woman who had DS and a
      history of adult-onset epilepsy and was admitted to our hospital with recurrent
      seizures. After admission, her ammonia levels fluctuated without any apparent
      cause, and dynamic computed tomography revealed a portosystemic shunt. The
      findings suggest that her seizures possibly precipitated from hyperammonemia
      secondary to a portosystemic shunt, and we reviewed the relevant literature.
      METHODS: We conducted PubMed, Web of Science, and EMBASE searches without
      language restrictions for articles published between 1970 and February 2013.
      RESULTS: In addition to the present case, 7 cases were ultimately included in
      this review. Four patients were newborns, 2 patients were 1 month old, and 1
      patient was 3 years old. No adult cases were described until now. CONCLUSION:
      Adult patients with DS diagnosed with epilepsy are not routinely assessed for
      portosystemic venous shunts. Measuring ammonia levels in patients with DS the day
      after admission would help detect portosystemic shunts, even if the patients have
      been previously diagnosed with epilepsy. PRACTICE IMPLICATIONS: If ammonia levels
      fluctuate without any apparent cause after seizure, dynamic computed tomography
      should be performed, especially for patients with DS, whether or not they have
      been previously diagnosed with epilepsy.

PMID- 24035600
TI  - Continuation rates of levetiracetam in children from the EULEVp cohort study.
AB  - BACKGROUND: Since indication extension to children data regarding the
      effectiveness of levetiracetam in paediatric patients remains limited. AIMS:
      Investigate the real-life effectiveness of levetiracetam in paediatric patients.
      METHODS: Epileptic children (<16 years) who had initiated levetiracetam between 1
      October 2006 and 31 March 2007 were included and followed for 1 year by hospital
      or non-hospital neurologists practising in France. RESULTS: Among the 156
      identified children, 147 were analysed: 51.7% were female, and mean (SD) age was
      9.2 years (4.2). Most patients had either partial symptomatic (30.6%) or partial
      cryptogenic (26.5%) epilepsy, 92.5% experienced seizures during the 6 months
      preceding levetiracetam initiation, and 19.2% were on levetiracetam alone at
      initiation. One-year levetiracetam continuation rate was estimated to be 72.0%
      (95%CI [63.8; 78.6]). Of the 104 children continuing levetiracetam treatment at
      end of study, 31.7% were seizure-free during the last six months of follow-up,
      and 23.1% on levetiracetam alone. Discontinuation of levetiracetam (n = 41) was
      mainly for insufficient efficacy (58.5% of those concerned). CONCLUSIONS: In real
      life clinical practice important treatment retention and non-negligible reduction
      of seizure frequency may be expected.

PMID- 24035601
TI  - Oxytocin and psychotherapy: keeping context and person in mind.

PMID- 24035602
TI  - Not disappointed by anxiety: a reply to Cardoso and Ellenbogen's commentary
      "Oxytocin and psychotherapy: keeping context and person in mind".

PMID- 24035603
TI  - Pediatric robotic-assisted laparoscopic ipsilateral ureteroureterostomy in a
      duplicated collecting system.
AB  - INTRODUCTION AND OBJECTIVE: Duplex renal collecting system is a common congenital
      anomaly in the pediatric population. The superior moiety ureter is often
      associated with an ectopic insertion. A common site of insertion is the urethra,
      which results in continuous incontinence. A novel repair for this abnormality is
      a robotic assisted laparoscopic ipsilateral ureteroureterostomy with end to side
      anastomosis. This teaching video will demonstrate positioning and operative
      technique for this procedure. PATIENT AND METHODS: This is the case of a 5-year
      old girl who presented with lifelong continuous urinary incontinence. Workup
      revealed a duplicated collecting system with a functional superior moiety and
      ectopic ureter inserting into the urethra. A laparoscopic ipsilateral
      ureteroureterostomy was performed using a robotic surgical system. RESULTS: After
      docking the robotic surgical system, the duplicated collecting system was
      identified and an ipsilateral ureteroureterostomy was performed. The patient
      tolerated the procedure well and the ultrasound on follow up revealed no residual
      hydronephrosis. CONCLUSION: The accompanying teaching video shows appropriate
      positioning and operative technique for a robotic-assisted laparoscopic
      ureteroureterostomy. This innovative and minimally invasive technique is a safe
      and feasible approach to repair a duplex collecting system with an ectopic ureter
      in the pediatric population.

PMID- 24035605
TI  - Identification of multiple and distinct defects in prostaglandin biosynthetic
      pathways in eutopic and ectopic endometrium of women with endometriosis.
AB  - OBJECTIVE: To investigate prostaglandin (PG) biosynthesis and catabolism pathways
      in eutopic and ectopic endometrium of women with endometriosis. DESIGN:
      Retrospective study. SETTING: Human reproduction research laboratory. PATIENT(S):
      Forty-five women with endometriosis and 29 normal controls. INTERVENTION(S):
      Endometrial and endometriotic tissue samples were obtained during laparoscopic
      surgery. MAIN OUTCOME MEASURE(S): Cyclo-oxygenases (Coxs 1 and 2), PGE2 synthases
      (microsomal [m] PGES 1 and 2 and cytosolic [c] PGES), PGF2alpha synthases
      (aldoketoreductase [AKR]-1C3 and AKR-1B1), and the PG catabolic enzyme 15
      hydroxyprostaglandin dehydrogenase messenger RNA expression by quantitative real
      time polymerase chain reaction and protein localization by immunohistochemistry.
      RESULT(S): This study showed a marked increase in the key PG biosynthesis enzymes
      Cox-2, mPGES-1, mPGES-2, cPGES, and AKR-1C3 in ectopic endometrial tissue of
      women with endometriosis, particularly in the earliest and most active stages of
      the disease, without a noticeable change in the expression of the PG catabolic
      enzyme 15-hydroxyprostaglandin dehydrogenase. Meanwhile, the significant increase
      in rate-limiting Cox-2 expression upstream was correlated downstream by a
      significant stage- and cycle phase-dependent decrease in the terminal specific
      synthase mPGES-2, thereby revealing the presence of counter-regulatory
      mechanisms, which operate in the eutopic endometrium of women with endometrium
      but seem to be lacking in the ectopic implantation sites. CONCLUSION(S): This
      study reveals for the first time multiple defects in PG biosynthesis pathways,
      which differ between eutopic intrauterine and ectopic endometrial tissues and
      may, owing to the wide spectrum of PG properties, contribute to the initial steps
      of endometrial tissue growth and development and have an important role to play
      in the pathogenesis and symptoms of this disease.

PMID- 24035606
TI  - The two sides of HER2/neu: immune escape versus surveillance.
AB  - The oncogene HER2 is one of the prototypes for targeted immunotherapy of cancer
      using both monoclonal antibodies as well as T cell based immunotherapies.
      Effective humoral and cellular immune responses against HER2 can be induced, but
      these responses can be influenced by the effects of this oncogene on the target
      tumor cells. The processes involved in HER2-mediated adaptive and innate immunity
      and the molecular mechanisms underlying the escape of HER2-expressing tumor cells
      from immune surveillance, particularly from cytotoxic T cells, are discussed.
      Implementing this knowledge in clinical trials to revert immune evasion may help
      optimize immunotherapies directed against HER2-expressing tumors. 

PMID- 24035604
TI  - Prospective evaluation of nighttime hot flashes during pregnancy and postpartum.
AB  - OBJECTIVE: To determine the prevalence, course, and risk factors for nighttime
      hot flashes during the pregnancy and postpartum periods. DESIGN: Clinical
      interview, physical measurements, and questionnaires administered at weeks 20,
      30, and 36 of pregnancy and weeks 2, 12, 26, and 52 after delivery. SETTING:
      Academic medical setting. PATIENT(S): 429 women. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Nighttime hot flashes. RESULT(S): Thirty-five percent of
      women reported nighttime hot flashes during pregnancy and 29% after delivery. In
      multivariable binomial mixed effects models, women who were younger (per year:
      odds ratio [OR] 0.94; 95% confidence interval [CI], 0.88-0.99), had a higher
      prepregnancy body mass index (per unit increase: OR 1.05; 95% CI, 1.01-1.10), and
      had less than a college education (OR 2.58; 95% CI, 1.19-5.60; vs. >= college)
      were more likely to report nighttime hot flashes during pregnancy. Higher
      depressive symptoms were associated with nighttime hot flashes during pregnancy
      (per unit increase: OR 1.08; 95% CI, 1.04-1.13) and the postpartum period (OR
      1.19; 95% CI, 1.14-1.25, multivariable models). CONCLUSION(S): Hot flashes,
      typically considered a menopausal symptom, were reported by over a third of women
      during pregnancy and/or the postpartum period. The predictors of these hot
      flashes, including depressive symptoms, low education, and higher body mass index
      are similar to those experienced during menopause. Future work should investigate
      the role of hormonal and affective factors in hot flashes during pregnancy and
      postpartum.

PMID- 24035607
TI  - Clinical practice guidelines for the management of invasive Candida infections in
      adults in the Middle East region: Expert panel recommendations.
AB  - Invasive Candida infections contribute to significant morbidity and mortality in
      patients with healthcare-associated infections. They represent a major burden on
      the public health system, and are challenging to diagnose and treat. A
      multidisciplinary expert panel critically reviewed available evidence to provide
      consensus recommendations for the management of invasive Candida infections in
      the Middle East. Based on diagnosis, recommendations were provided for the
      management of Candida infections in non-neutropenic and neutropenic patients.
      Polyenes (amphotericin B-deoxycholate [AmB-d] and lipid formulations amphotericin
      B [LFAmB]), triazoles (fluconazole, itraconazole and voriconazole), echinocandins
      (caspofungin, anidulafungin, and micafungin) and flucytosine are the recommended
      categories of antifungal agents for treatment of Candida infections.
      Echinocandins are preferred for treatment of proven and suspected Candida
      infections, especially in critically ill patients or those with previous exposure
      to azoles. Recommendations were also provided for infections caused by specific
      Candida species as well as management of different disease conditions. The
      experts highlighted that the guidelines should be used along with clinical
      judgment. Given the paucity of published data from the region, research in the
      form of randomized clinical trials should be given priority.

PMID- 24035609
TI  - Study on the electromechanical coupling coefficient of Rayleigh-type surface
      acoustic waves in semi-infinite piezoelectrics/non-piezoelectrics superlattices.
AB  - The electromechanical coupling coefficient of Rayleigh-type surface acoustic
      waves in semi-infinite piezoelectrics/non-piezoelectrics superlattices is
      investigated by the transfer matrix method. Research results show the high
      electromechanical coupling coefficient can be obtained in these systems. The
      optimization design of it is also discussed fully. It is significantly influenced
      by electrical boundary conditions on interfaces, thickness ratios of
      piezoelectric and non-piezoelectric layers, and material parameters (such as
      velocities of pure longitudinal and transversal bulk waves in non-piezoelectric
      layers). In order to obtain higher electromechanical coupling coefficient,
      shorted interfaces, non-piezoelectric materials with large velocities of
      longitudinal and transversal bulk waves, and proper thickness ratios should be
      chosen. 

PMID- 24035608
TI  - Experimental study of underwater transmission characteristics of high-frequency
      30 MHz polyurea ultrasonic transducer.
AB  - In this paper, we present the transmission characteristics of a polyurea
      ultrasonic transducer operating in water. In this study, we used a polyurea
      transducer with fundamental resonance at approximately 30 MHz. Firstly, acoustic
      pressure radiated from the transducer was measured using a hydrophone, which has
      a diameter of 0.2 mm. The transmission characteristics such as relative
      bandwidth, pulse width, and acoustic sensitivity were calculated from the
      experimental results. The results of the experiment showed a relative bandwidth
      of 50% and a pulse width of 0.061 MUs. The acoustic sensitivity was 0.60 kPa/V
      with good linearity, where the correlation coefficient R in the fitting
      calculation was 0.996. A maximum pressure of 13.1 kPa was observed when the
      transducer was excited at a zero-to-peak voltage of 21 V. Moreover, we
      experimentally verified the results. The results of the pulse/echo experiment
      showed that the estimated diameters of the copper wires were 458 and 726 MUm,
      where the differences between the actual and measured values were 15% and 4%,
      respectively. Acoustic streaming was also observed so that a particle velocity
      map was estimated by particle image velocimetry (PIV). The sound pressure
      calculated from the particle velocity obtained by PIV showed good agreement with
      the acoustic pressure measured using the hydrophone, where the differences
      between the calculated and measured values were 12-19%.

PMID- 24035610
TI  - Low- and high-frequency nonlinear acoustic phenomena in a magnesite.
AB  - The results of experimental and theoretical studies of nonlinear acoustic
      phenomena (amplitude-dependent losses, resonant frequency shifts, damping of weak
      ultrasonic pulses and their carrier frequency phase delay under action of a
      powerful low-frequency pumping wave as well as amplitude-phase self-action of the
      finite-amplitude ultrasonic pulses) in a magnesite rod are presented. Analytical
      description of the observed phenomena was carried out within the frameworks of
      the phenomenological state equations that contain low-frequency hysteretic
      nonlinearity and both high-frequency dissipative and elastic nonlinearity. From
      comparison of experimental and analytical amplitude-frequency dependences of
      nonlinear phenomena, the values of magnesite acoustic nonlinearity parameters
      were determined. The frequency dependences have been discovered for hysteretic
      (in a range 3.6-17.2 kHz) as well as dissipative and elastic nonlinearity (in a
      range 50-370 kHz).

PMID- 24035611
TI  - Target-controlled induction with 2.5% sevoflurane does not avoid the risk of
      electroencephalographic abnormalities.
AB  - BACKGROUND: Epileptiform discharges (ED) can occur during sevoflurane induction,
      especially in young female patients and when high alveolar concentrations are
      used. The aim of this study was to evaluate whether low sevoflurane concentration
      reduces the occurrence of ED in female patients. METHODS: Thirty-four female
      patients scheduled for minor gynecological surgery were prospectively included
      and randomized in two groups. In group A, anesthesia was induced with sevoflurane
      inspired 8% manually set via the circuit of the Zeus((r)) (Drager Medical,
      Lubeck, Germany) anesthesia workstation (fresh gas flow 8L.min(-1)) for 2min and
      then 2.5%. In group B, induction was performed by target-controlled inhalation
      with a target end-tidal concentration of sevoflurane set at 2.5% (fresh gas flow
      in auto-control mode). Electroencephalogram (EEG) was recorded in the operating
      room throughout induction till two min after intubation and analyzed off-line by
      a neurophysiologist blinded to the randomization. RESULTS: ED occurred in five
      patients (15%): one in group A and four in group B (P>0.05). ED occurred with a
      median delay of 303 s [25-75 interquartiles: 135-418] and the median duration of
      ED episode was 13 s [3-78]. Fifteen patients had abnormal movements without
      simultaneous EEG abnormality. CONCLUSION: Induction of anesthesia with low target
      concentration of sevoflurane (2.5%) fails to totally prevent the occurrence of ED
      in young female patients and should be used carefully in this population.

PMID- 24035612
TI  - Transthyretin is dysregulated in preeclampsia, and its native form prevents the
      onset of disease in a preclinical mouse model.
AB  - Preeclampsia is a major pregnancy complication with potential short- and long
      term consequences for both mother and fetus. Understanding its pathogenesis and
      causative biomarkers is likely to yield insights for prediction and treatment.
      Herein, we provide evidence that transthyretin, a transporter of thyroxine and
      retinol, is aggregated in preeclampsia and is present at reduced levels in sera
      of preeclamptic women, as detected by proteomic screen. We demonstrate that
      transthyretin aggregates form deposits in preeclampsia placental tissue and cause
      apoptosis. By using in vitro approaches and a humanized mouse model, we provide
      evidence for a causal link between dysregulated transthyretin and preeclampsia.
      Native transthyretin inhibits all preeclampsia-like features in the humanized
      mouse model, including new-onset proteinuria, increased blood pressure,
      glomerular endotheliosis, and production of anti-angiogenic factors. Our findings
      suggest that a focus on transthyretin structure and function is a novel strategy
      to understand and combat preeclampsia.

PMID- 24035613
TI  - miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.
AB  - Preeclampsia is characterized by hypertension and proteinuria in pregnant women.
      Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal
      morbidity and mortality. Although delivery, often premature, is the only known
      cure, early targeted interventions may improve maternal and fetal outcomes.
      Successful intervention requires a better understanding of the molecular etiology
      of preeclampsia and the development of accurate methods to predict women at risk.
      To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic
      placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression
      reduced trophoblast invasion, a process necessary for uteroplacental perfusion,
      in an extracellular signal-regulated kinase/mitogen-activated protein kinase
      dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore,
      given that the placenta secretes miRNAs into the maternal circulation, we tested
      if serum expression of miR-210 was associated with the disease. We measured miR
      210 expression in two clinical studies: a case-control study and a prospective
      cohort study. Serum miR-210 expression was significantly associated with a
      diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves =
      0.81) and was predictive of the disease, even months before clinical diagnosis (P
      < 0.0001, area under the receiver operator curve = 0.89). Hence, we conclude that
      aberrant expression of miR-210 may contribute to trophoblast function and that
      miR-210 is a novel predictive serum biomarker for preeclampsia that can help in
      identifying at-risk women for monitoring and treatment. 

PMID- 24035615
TI  - A rare presentation of a large extra-abdominal desmoid tumor of the posterior
      neck and back.
AB  - OBJECTIVE: To describe a difficult case of a large extra-abdominal desmoid
      fibroma of the posterior neck and back; to discuss the pathologic findings and
      treatment options of this case and to review the current literature for a rare
      presentation of this disease. METHOD: A case report and review of the current
      relevant English literature, carried out using PubMed Medline, are presented.
      RESULTS: We present a challenging case in which a locally invasive desmoid of the
      posterior neck and back had grown to such an extent that complete surgical
      excision in one procedure was not possible. CONCLUSION: Extra-abdominal desmoid
      fibromas are rare tumors with multiple treatment options. The literature supports
      incomplete surgical resection when necessary to reduce postoperative morbidity.
      Further options described for residual or recurrent disease include repeat
      surgical excision, radiation therapy, and possible chemotherapy. For particularly
      large tumors, close observation and a planned second stage procedure are an
      appropriate choice.

PMID- 24035614
TI  - Tension pneumocephalus: an extremely small defect leading to an extremely serious
      problem.
AB  - BACKGROUND: Pneumocephalus is a pathology characterized by air influx into the
      intracranial region. It may occur after head trauma and rarely after endoscopic
      sinus surgery. As the amount of air increases, this can cause neurological
      disorders with a mass effect and this condition is called tension pneumocephalus.
      CASE DESCRIPTION: Our case is a 65-year-old woman. Tension pneumocephalus
      developed 12h after endoscopic sinus surgery performed for nasal polypectomy.
      Since tension pneumocephalus developed very rapidly in the patient creating a
      herniation table, the patient was taken to theater immediately. A burr-hole was
      drilled into the skull and a small defect in the ethmoid roof was closed with a
      layered closure technique. Post-operative conservative treatment was applied (bed
      rest, raising the bed head, meningitis prophylaxis, loop diuretics, abstaining
      from maneuvers increasing the Valsalva). DISCUSSION: In the literature, it is
      stated that, in the case of a small defect, spontaneous resolution may be
      provided with conservative treatment, but as the size of the defect increases,
      neurological effects will occur more quickly and be more obvious. In our case, a
      herniation table developed leading to neurological and vital problems in a more
      rapid and more obvious way than in other tension pneumocephalus cases developing
      after endoscopic sinus surgery. We consider that this situation is related to a
      very small defect size. CONCLUSION: Tension pneumocephalus is a complication
      rarely seen after endoscopic sinus surgery, but if it is not treated immediately,
      it may give rise to serious morbidity and mortality concerns. The clinical course
      developing after tension pneumocephalus may be very serious when very small
      defects are involved.

PMID- 24035616
TI  - Parathyroidectomy improves symptomatology and quality of life in patients with
      secondary hyperparathyroidism.
AB  - BACKGROUND: The parathyroidectomy assessment of symptoms (PAS) score was designed
      initially for primary hyperparathyroidism to provide a specific symptom
      assessment and was validated later in secondary and tertiary hyperparathyroidism.
      The aim of our study was to evaluate changes in the PAS scores and quality of
      life before and after parathyroidectomy for secondary hyperparathyroidism.
      METHODS: This prospective study included 49 consecutive patients who underwent
      parathyroidectomy for secondary hyperparathyroidism. The PAS and Short Form (SF)
      36 questionnaires were completed before parathyroidectomy and at 12 months
      postoperatively. RESULTS: All 13 symptoms included in the PAS score improved
      significantly. The mean +/- standard deviation PAS score decreased from 545 +/-
      263 to 284 +/- 201 (P < .0001) after parathyroidectomy. Quality of life was
      enhanced in both physical (40.3 +/- 17.1 to 59.0 +/- 14.9; P < .0001) and mental
      (47.6 +/- 17.1 to 63.7 +/- 13.0; P < .0001) components. The PAS score was
      inversely correlated with the SF-36 global score preoperatively and
      postoperatively (r(2) = 0.48 and 0.25; P < .001). The change in PAS score also
      correlated with the change in SF-36 global score (r(2) = 0.29; P < .001).
      Multiple linear regression analysis showed that preoperative PAS score and bone
      mineral density T-score were predictors of the decrease in PAS score.
      Preoperative SF-36 global score and intact parathyroid hormone levels were
      predictors of the increment in SF-36 score. CONCLUSION: The symptom burden of
      secondary hyperparathyroidism has a negative impact on a patient's quality of
      life. Parathyroidectomy is associated with a marked improvement in symptoms and
      quality of life.

PMID- 24035617
TI  - Distal side-branch technique: a new use for the Tornus(r) Catheter.
AB  - Percutaneous coronary intervention (PCI) outcomes of chronic total occlusions
      (CTO) lesions have improved in recent years due to a better understanding of the
      physiopathology of the disease, more effective techniques and improvement in the
      design of new devices. We describe a new use of the Tornus(r) Catheter in the
      anterograde approach for CTO treatment. 

PMID- 24035618
TI  - Is cup positioning challenged in hips previously treated with periacetabular
      osteotomy?
AB  - After periacetabular osteotomy (PAO), some patients develop osteoarthritis with
      need of a total hip arthroplasty (THA). We evaluated the outcome of THA following
      PAO and explored factors associated with inferior cup position and increased
      polyethylene wear. Follow-up were performed 4 to 10 years after THA in 34
      patients (38 hips) with previous PAO. Computer analysis evaluated cup position
      and wear rates. No patient had dislocations or revision surgery. Median scores
      were: Harris hip 96, Oxford hip 38 and WOMAC 78. Mean cup anteversion and
      abduction angles were 22 degrees  (range 7 degrees -43 degrees ) and 45 degrees 
      (range 28 degrees -65 degrees ). Outliers of cup abduction were associated with
      persisting dysplasia (CE <25 degrees ). THA after PAO can produce excellent
      clinical results. Persisting acetabular dysplasia following PAO may lead surgeons
      to place the acetabular component in excessive cup abduction, and this tendency
      should be recognized at the time of the PAO.

PMID- 24035619
TI  - Periprosthetic femoral fracture--a biomechanical comparison between Vancouver
      type B1 and B2 fixation methods.
AB  - Current clinical data suggest a higher failure rate for internal fixation in
      Vancouver type B1 periprosthetic femoral fracture (PFF) fixations compared to
      long stem revision in B2 fractures. The aim of this study was to compare the
      biomechanical performance of several fixations in the aforementioned fractures.
      Finite element models of B1 and B2 fixations, previously corroborated against in
      vitro experimental models, were compared. The results indicated that in treatment
      of B1 fractures, a single locking plate can be without complications provided
      partial weight bearing is followed. In case of B2 fractures, long stem revision
      and bypassing the fracture gap by two femoral diameters are recommended.
      Considering the risk of single plate failure, long stem revision could be
      considered in all comminuted B1 and B2 fractures. 

PMID- 24035620
TI  - Progranulin: at the interface of neurodegenerative and metabolic diseases.
AB  - Progranulin is a widely expressed, cysteine-rich, secreted glycoprotein
      originally discovered for its growth factor-like properties. Its subsequent
      identification as a causative gene for frontotemporal dementia (FTD), a
      devastating early-onset neurodegenerative disease, has catalyzed a surge of new
      discoveries about progranulin function in the brain. More recently, progranulin
      was recognized as an adipokine involved in diet-induced obesity and insulin
      resistance, revealing its metabolic function. We review here progranulin biology
      in both neurodegenerative and metabolic diseases. In particular, we highlight the
      growth factor-like, trophic, and anti-inflammatory properties of progranulin as
      potential unifying themes in these seemingly divergent conditions. We also
      discuss potential therapeutic options for raising progranulin levels to treat
      progranulin-deficient FTD, as well as the possible consequences of such
      treatment. 

PMID- 24035621
TI  - Characterization of thyroid cancer in mouse models using high-frequency
      quantitative ultrasound techniques.
AB  - Currently, the evaluation of thyroid cancer relies on the use of fine-needle
      aspiration biopsy, as non-invasive imaging methods do not provide sufficient
      levels of accuracy for the diagnosis of this disease. In this study, the
      potential of quantitative ultrasound methods for characterization of thyroid
      tissues was studied using a rodent model ex vivo. A high-frequency ultrasonic
      scanning system (40 MHz) was used to scan thyroids extracted from mice that had
      spontaneously developed thyroid lesions (cancerous or benign). Three sets of mice
      were acquired having different predispositions to developing three thyroid
      anomalies: C-cell adenoma, papillary thyroid carcinoma (PTC) and follicular
      variant papillary thyroid carcinoma (FV-PTC). A fourth set of mice that did not
      develop thyroid anomalies (normal mice) were used as controls. The backscatter
      coefficient was estimated from excised thyroid lobes the different mice. From the
      backscatter coefficient versus frequency (25-45 MHz), the effective scatterer
      diameter (ESD) and effective acoustic concentration (EAC) were estimated. From
      the envelope of the backscattered signal, the homodyned K distribution was used
      to estimate the k parameter (ratio of coherent to incoherent signal energy) and
      the MU parameter (number of scatterers per resolution cell). Statistically
      significant differences were observed between cancerous thyroids and normal
      thyroids based on the ESD, EAC and MU parameters. The mean ESD values were 18.0
      +/- 0.92, 15.9 +/- 0.81 and 21.5 +/- 1.80 MUm for the PTC, FV-PTC and normal
      thyroids, respectively. The mean EAC values were 59.4 +/- 1.74, 62.7 +/- 1.61 and
      52.9 +/- 3.42 dB (mm(-3)) for the PTC, FV-PTC and normal thyroids, respectively.
      The mean MU values were 2.55 +/- 0.37, 2.59 +/- 0.43 and 1.56 +/- 0.99 for the
      PTC, FV-PTC and normal thyroids, respectively. Statistically significant
      differences were observed between cancerous thyroids and C-cell adenomas based on
      the ESD and EAC parameters, with an estimated ESD value of 21.3 +/- 1.50 MUm and
      EAC value of 54.7 +/- 2.24 dB mm(-3) for C-cell adenomas. These results suggest
      that high-frequency quantitative ultrasound may enhance the ability to detect and
      classify diseased thyroid tissues.

PMID- 24035622
TI  - Paraffin-gel tissue-mimicking material for ultrasound-guided needle biopsy
      phantom.
AB  - Paraffin-gel waxes have been investigated as new soft tissue-mimicking materials
      for ultrasound-guided breast biopsy training. Breast phantoms were produced with
      a broad range of acoustical properties. The speed of sound for the phantoms
      ranged from 1425.4 +/- 0.6 to 1480.3 +/- 1.7 m/s at room temperature. The
      attenuation coefficients were easily controlled between 0.32 +/- 0.27 dB/cm and
      2.04 +/- 0.65 dB/cm at 7.5 MHz, depending on the amount of carnauba wax added to
      the base material. The materials do not suffer dehydration and provide adequate
      needle penetration, with a Young's storage modulus varying between 14.7 +/- 0.2
      kPa and 34.9 +/- 0.3 kPa. The phantom background material possesses long-term
      stability and can be employed in a supine position without changes in geometry.
      These results indicate that paraffin-gel waxes may be promising materials for
      training radiologists in ultrasound biopsy procedures.

PMID- 24035623
TI  - Ultrasound directs a transposase system for durable hepatic gene delivery in
      mice.
AB  - Our aim was to evaluate the delivery of transposase-based vectors by ultrasound
      targeted microbubble destruction (UTMD) in mice. DNA vectors were attached to
      cationic lipid microbubbles (1-3 MUm in diameter), injected intravenously and
      delivered to the liver by destruction of the carrier bubbles with ultrasound in
      burst mode at 1.0 MHz, 20-MUs pulse duration, 10-Hz pulse repetition frequency
      and ~1.3-MPa acoustic peak negative pressure. We evaluated the expression and
      genomic integration of conventional (pcDNA3) and piggyBac transposase-based
      (pmGENIE) reporter vectors. In vivo, we observed UTMD-mediated liver-specific
      expression of pmGENIE for an average of 24 d, compared with 4 d with pcDNA3.
      Reporter expression was located predominately near blood vessels initially,
      whereas expression after 3 d was more evenly distributed through the parenchyma
      of the liver. We confirmed random genomic integration for pmGENIE in vitro;
      however, integration events for pmGENIE in vivo were targeted to specific areas
      of chromosome 14. Our results suggest that a combination of UTMD and non-viral
      DNA transposase vectors can mediate weeks of hepatic-specific gene transfer in
      vivo, and analyses performed by non-restrictive linear amplification-mediated
      (nrLAM) polymerase chain reaction, cloning and sequencing identify an unexpected
      tropism for integration within a specific sequence on chromosome 14 in mice. UTMD
      delivery of transgenes may be useful for the treatment of hepatic gene deficiency
      disorders.

PMID- 24035624
TI  - Acoustic radiation force impulse imaging with virtual touch tissue
      quantification: measurements of normal breast tissue and dependence on the degree
      of pre-compression.
AB  - Acoustic radiation force impulse imaging (ARFI) with Virtual Touch tissue
      quantification (VTTQ) enables the determination of shear wave velocity in meters
      per second (m/s). We investigated shear wave velocity in normal breast tissue and
      analyzed the influence of the degree of pre-compression on the measurements. In
      repeated measurements and with normal pre-compression, the mean shear wave
      velocity in breast parenchyma was significantly higher than that in breast
      adipose tissue (3.33 +/- 1.18 m/s vs. 2.90 +/- 1.10 m/s; p < 0.001; 712
      measurements in 89 patients). Furthermore, we found a significant positive
      correlation between degree of pre-compression and velocity measurements. Shear
      wave velocities with low, moderate and high pre-compression were 1.89, 3.18 and
      4.39 m/s in parenchyma, compared with 1.46, 2.55 and 3.64 m/s in adipose tissue,
      respectively (p < 0.001; 360 measurements in 60 patients). VTTQ of breast tissue
      is a feasible method with high accuracy; however, the degree of pre-compression
      applied may significantly influence the measurements.

PMID- 24035626
TI  - Individual and combined diagnostic accuracy of ultrasound diagnosis, ultrasound
      guided fine-needle aspiration and polymerase chain reaction in identifying
      tuberculous lymph nodes in the neck.
AB  - The aim of this study was to assess the efficacy of, both individually and in
      combination, ultrasound (US) diagnosis, US-guided fine-needle aspiration (US-FNA)
      and polymerase chain reaction (PCR) in diagnosing tuberculous lymph nodes in the
      neck (i.e., tuberculous cervical lymph nodes [TCLs]). Eighty-two patients who
      underwent US diagnosis, US-FNA and PCR for clinical suspicion of TCLs were
      enrolled. Of the 82 patients, 31 were confirmed as having TCLs. The sensitivity,
      specificity, positive and negative predictive values and accuracy of US
      diagnosis, US-FNA and PCR were 93.5%, 76.5%, 70.7%, 95.1% and 82.9%; 64.5%,
      98.0%, 95.2%, 82.0% and 85.4%; and 100%, 96.1%, 93.9%, 100% and 97.6%,
      respectively. The diagnostic values of PCR alone and in combination with US-FNA
      were found to be higher than those of other methods. No US feature with high
      sensitivity and specificity was identified. 

PMID- 24035627
TI  - Diagnostic performance of automated breast ultrasound as a replacement for a hand
      held second-look ultrasound for breast lesions detected initially on magnetic
      resonance imaging.
AB  - To evaluate the diagnostic performance of automated breast ultrasound (ABUS)
      after breast magnetic resonance imaging (MRI) as a replacement for hand-held
      second-look ultrasound (HH-SLUS), we evaluated 58 consecutive patients with
      breast cancer who had additional suspicious lesions on breast MRI. All patients
      underwent HH-SLUS and ABUS. Three breast radiologists evaluated the
      detectability, location, characteristics and conspicuity of lesions on ABUS. We
      also evaluated inter-observer variability and compared the results with HH-SLUS
      results. Eighty additional suspicious lesions were identified on breast MRI.
      Fifteen of the 80 lesions (19%) were not detected on HH-SLUS. Eight of the 15
      lesions (53%) were detected on ABUS, whereas the remaining 7 were not detected on
      ABUS. Among the 65 lesions detected on HH-SLUS, only 3 lesions were not detected
      on ABUS. The intra-class correlation coefficients for lesion location and size
      all exceeded 0.70, indicating high reliability. Moderate to fair agreement was
      found for mass shape, orientation, margin and Breast Imaging Reporting and Data
      System (BI-RADS) final assessment. Therefore, ABUS can reliably detect additional
      suspicious lesions identified on breast MRI and may help in the decision on
      biopsy guidance method (US vs. MRI) as a replacement tool for HH-SLUS. 

PMID- 24035625
TI  - High-throughput, high-frequency 3-D ultrasound for in utero analysis of embryonic
      mouse brain development.
AB  - With the emergence of the mouse as the predominant model system for studying
      mammalian brain development, in utero imaging methods are urgently required to
      analyze the dynamics of brain growth and patterning in mouse embryos. To address
      this need, we combined synthetic focusing with a high-frequency (38-MHz) annular
      array ultrasound imaging system for extended depth-of-field, coded excitation for
      improved penetration and respiratory-gated transmit/receive. This combination
      allowed non-invasive in utero acquisition of motion-free 3-D data from individual
      embryos in approximately 2 min, and data from four or more embryos in a pregnant
      mouse in less than 30 min. Data were acquired from 148 embryos spanning 5 d of
      early to mid-gestational stages of brain development. The results indicated that
      brain anatomy and cerebral vasculature can be imaged with this system and that
      quantitative analyses of segmented cerebral ventricles can be used to
      characterize volumetric changes associated with mouse brain development.

PMID- 24035628
TI  - Isovolumetric elasticity alteration in the human heart detected by in vivo time
      harmonic elastography.
AB  - Time harmonic elastography (THE) has recently been introduced for measurement of
      the periodic alteration in myocardial shear modulus based on externally induced
      low-frequency acoustic vibrations produced by a loudspeaker. In this study, we
      propose further developments of cardiac THE toward a clinical modality including
      integration of the vibration source into the patient bed and automated parameter
      extraction from harmonic shear wave amplitudes, wall motion profiles and
      synchronized electrocardiographic records. This method has enabled us to evaluate
      the delay between wall motion and wave amplitude alteration for the measurement
      of isovolumetric times of elasticity alteration during contraction (tau(C)) and
      relaxation (tau(R)) in a group of 32 healthy volunteers. On average, the wave
      amplitudes changed between systole and diastole by a factor of 1.7 +/- 0.3, with
      a tau(C) of 137 +/- 61 ms and a tau(R) of 68 +/- 73 ms, which agrees with results
      obtained with the more time-consuming and expensive cardiac magnetic resonance
      elastography. Furthermore, because of the high sampling rate, elasto-morphometric
      parameters such as transition times and the area of wave amplitude-cardiac motion
      cycles can be processed in an automated way for the future clinical detection of
      myocardial relaxation abnormalities.

PMID- 24035629
TI  - Renal parenchymal thickness as a measure of renal growth in low-birth-weight
      infants versus normal-birth-weight infants.
AB  - Low birth weight (LBW, <2500 g) infants have a reduced number of glomeruli and
      nephrons and, therefore, smaller kidneys. The purpose of this pilot study was to
      determine whether renal parenchymal thickness might be a better indicator of
      renal growth. We carried out a pilot study over 12 mo to determine whether renal
      parenchymal thickness could be used to detect differences in renal growth between
      LBW and normal birth weight (NBW, 2500-4500 g) infants. Thirty-eight term infants
      (12 LBW and 26 NBW) underwent renal ultrasound. Parenchymal thickness, length,
      transverse diameter and antero-posterior diameter were measured. Mean renal
      parenchymal thickness was significantly lower in LBW infants than in NBW infants.
      Renal parenchymal thickness was closely correlated with an increase in renal
      volume (r = 0.76, p < 0.0001). Renal parenchymal thickness is a single
      measurement that could potentially be a more useful and accurate approach to
      monitoring renal growth in growth-restricted infants than renal volume.

PMID- 24035630
TI  - Accuracy of an automated breast volume ultrasound system for assessment of the
      pre-operative extent of pure ductal carcinoma in situ: comparison with a
      conventional handheld ultrasound examination.
AB  - The goal of the study described here was to compare the accuracy of an automated
      breast volume scanner (ABVS) with that of hand-held ultrasound (HHUS) in
      assessing the pre-operative extent of pure ductal carcinoma in situ (DCIS). This
      prospective study consisted of 33 patients with histopathologically proven pure
      DCIS who received conventional HHUS and ABVS examinations. The discrepancy and
      correlation coefficients were calculated to assess differences in sizes
      determined by imaging and histopathologic examination. Mean age was 51.8 y. Mean
      lesion size as assessed with the ABVS did not differ significantly from that
      determined by histopathology. Lesion size was adequately estimated, under
      estimated or over-estimated with the ABVS in 64%, 15% and 21% of patients, and
      with HHUS in 42%, 15% and 42%, respectively (p < 0.05). The coefficient of
      correlation between histopathologic and ABVS measurements was higher than that
      between histopathologic and HHUS measurements. The ABVS appears to assess the
      extent of the lesion better than HHUS and can provide more accurate information
      pre-operatively. 

PMID- 24035631
TI  - Do margins matter? The influence of positive surgical margins on prostate cancer
      specific mortality.
AB  - BACKGROUND: Positive surgical margins (PSMs) in radical prostatectomy (RP)
      specimens are a frequent indication for adjuvant radiotherapy and are used as a
      measure of surgical quality. However, the association between PSMs and prostate
      cancer-specific mortality (CSM) is poorly defined. OBJECTIVE: Analyze the
      association of PSMs with CSM, adjusting for fixed and time-dependent parameters.
      DESIGN, SETTING, AND PARTICIPANTS: Fine and Gray competing risk regression
      analysis was used to model the clinical data and follow-up information of 11,521
      patients treated by RP between 1987 and 2005. Two extended models were used that
      adjusted for the use of postoperative radiotherapy, which was handled as a time
      dependent covariate. Postoperative radiotherapy was modeled as a single parameter
      and also as early and late therapy, based on the prostate-specific antigen level
      at the start of treatment (<=0.5 vs >0.5 ng/ml). INTERVENTION: RP for clinically
      localized prostate cancer and selective use of secondary local and/or systemic
      therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome measure was
      prostate cancer-specific mortality. RESULTS AND LIMITATIONS: The 15-yr CSM rates
      for patients with PSMs and negative surgical margins were 10% and 6%,
      respectively (p<0.001). No significant association between PSM and CSM was
      observed in the conventional model with fixed covariates (hazard ratio [HR]:
      1.04; 95% confidence interval [CI], 0.7-1.5; p=0.8) or in the two extended models
      that adjusted for postoperative radiotherapy (HR: 0.96; 95% CI, 0.7-1.4; p=0.9),
      or early and late postoperative radiotherapy (HR: 1.01; 95% CI, 0.7-1.4; p=0.9).
      CONCLUSIONS: PSMs alone are not associated with a significantly increased risk of
      CSM within 15 yr of RP. However, urologists should continue to strive to avoid
      PSMs, as they increase a man's risk of biochemical recurrence and need for
      secondary therapy and may be a source of considerable patient anxiety.

PMID- 24035632
TI  - Predictors of pathologic progression on biopsy among men on active surveillance
      for localized prostate cancer: the value of the pattern of surveillance biopsies.
AB  - BACKGROUND: A better understanding of the independent predictors of disease
      progression for prostate cancer (PCa) patients is needed to improve the selection
      of ideal candidates for active surveillance (AS) and refine the surveillance
      regimen. OBJECTIVE: To examine the association of clinical and pathologic
      characteristics, as well as patterns of surveillance biopsy results, with the
      risk of progression in men on AS. DESIGN, SETTING, AND PARTICIPANTS: The
      retrospective study consisted of men with PCa who were on AS in the prospectively
      maintained University of California, San Francisco, institutional database from
      1996 to 2011. Strict criteria for AS were prostate-specific antigen (PSA) <=10
      ng/ml, clinical stage T1 or T2, biopsy Gleason grade 6, <33% positive cores, and
      <50% tumor in any single core. Men were then categorized based on results of
      their confirmatory surveillance biopsy. OUTCOME MEASUREMENTS AND STATISTICAL
      ANALYSIS: Disease progression was defined as an increase in Gleason grade and/or
      biopsy volume beyond prespecified cut points. Serial biopsy patterns over the
      course of surveillance were stratified by confirmatory biopsy findings: negative,
      positive without progression, and positive with progression. Multivariable
      logistic regression models were used to evaluate predictors of progression during
      AS. RESULTS AND LIMITATIONS: A total of 465 men met inclusion criteria (median
      follow-up: 51 mo). Of these men, 23% had negative confirmatory biopsies. Only 3%
      of the men (1 of 30) progressed by the fourth surveillance biopsy following a
      biopsy pattern of negative confirmatory and negative third biopsy findings.
      Negative confirmatory biopsy and lower PSA density (both p<0.01) were
      independently associated with decreased odds of biopsy progression at 3 yr. The
      main limitation of this study is its observational nature. CONCLUSIONS: The
      patterns of surveillance biopsy results yield additional important information in
      AS. Negative confirmatory biopsy and PSA density are important independent
      predictors of progression on AS and may be used to better counsel men opting for
      AS.

PMID- 24035633
TI  - Effect of lurasidone on neurocognitive performance in patients with
      schizophrenia: a short-term placebo- and active-controlled study followed by a 6
      month double-blind extension.
AB  - This double-blind study evaluated change in cognitive performance and functional
      capacity in lurasidone and quetiapine XR-treated schizophrenia patients over a 6
      week, placebo-controlled study, followed by a 6-month, double-blind extension.
      Cognitive performance and functional capacity were assessed with the CogState
      computerized cognitive battery and the UPSA-B. Analyses were conducted for all
      subjects, as well as the subsample whose test scores met prespecified validity
      criteria. No statistically significant differences were found for change in the
      composite neurocognitive score for lurasidone (80 mg/day and 160 mg/day) groups,
      quetiapine XR and placebo in the full sample at week 6. For the evaluable sample
      (N = 267), lurasidone 160 mg was superior to both placebo and quetiapine on the
      neurocognitive composite, while lurasidone 80 mg, quetiapine XR, and placebo did
      not differ. UPSA-B scores were superior to placebo at 6 weeks for all treatments.
      In the double-blind extension study, analysis of the full sample showed
      significantly better cognitive performance in the lurasidone (40-160 mg) group
      compared to the quetiapine XR (200-800 mg) group at both 3 and 6 months.
      Cognitive and UPSA-B total scores were significantly correlated at baseline and
      for change over time. This is the first study to date where the investigational
      treatment was superior to placebo on both cognitive assessments and a functional
      coprimary measure at 6 weeks, as well as demonstrated superiority to an active
      comparator on cognitive assessments at 6 weeks and at 6 months of extension study
      treatment. These findings require replication, but are not due to practice
      effects, because of the placebo and active controls.

PMID- 24035634
TI  - PTSD and obesity in the Detroit neighborhood health study.
AB  - OBJECTIVE: Posttraumatic stress disorder (PTSD) has been associated with adverse
      health consequences, including overweight, obesity and cardiovascular disease.
      African Americans, particularly women, have among the highest rates of overweight
      and obesity in the U.S. compared to other racial groups. High rates of violence
      exposure in urban African Americans may lead to the development of PTSD and
      increase risk for overweight and obesity. The current study investigated the
      comorbidity of lifetime PTSD and overweight/obesity in a population-based African
      American, urban sample. METHOD: Data were from 463 African American male and
      female participants of the Detroit Neighborhood Health Study. Multivariable
      logistic regression models estimated the impact of lifetime PTSD on risk for
      overweight and obesity. RESULTS: The prevalence of obesity was significantly
      higher among women (60.9%) than men (33.1%; P<.001). In sex-stratified models,
      after controlling for demographic variables, PTSD was associated obesity (odds
      ratio=4.4, 95% confidence interval: 1.3, 14.3) only among women. CONCLUSIONS:
      PTSD was associated with obesity, after controlling for confounding variables,
      among African American women. Results underscore the contribution of PTSD to
      obesity among African American women and the importance of addressing the
      physical health correlates of women with PTSD.

PMID- 24035635
TI  - Personality does not distinguish people with fibromyalgia but identifies
      subgroups of patients.
AB  - OBJECTIVES: The objectives were to compare the personality of fibromyalgia (FM)
      patients with other chronic painful and nonpainful disorders considering the
      confusion due to psychopathology and to assess the clustering of FM patients
      according to their personality profile. METHODS: Differences in the NEO Five
      Factor Inventory between FM, non-FM chronic pain and drug-resistant epileptic
      patients were assessed including the confounding effect of demographics and
      psychopathological status by multivariate regression analysis. Clustering of FM
      patients was assessed by two-step cluster analysis. Differences in clinical
      severity and psychosocial problems between subgroups and their outcome 6 months
      after multidisciplinary treatment were assessed. RESULTS: The final sample
      comprised 874 patients. Once the effect of confounding variables was considered,
      clinically nonsignificant differences in personality were observed between
      groups. FM patients could, however, be grouped into two clusters. Cluster 1 was
      characterized by higher neuroticism and lower extraversion and showed a worse
      pretreatment clinical state including more psychosocial problems. In spite of
      having reached a wider general improvement at 6-month follow-up, Cluster 1
      patients remained more anxious and depressed. CONCLUSIONS: Identifying
      personality-based subgroups of FM might allow implementing specific preventive
      strategies. FM treatment might be optimized by increasing medication compliance,
      improving therapeutic alliance and testing different therapeutic options and
      treatment sequencing for each personality subgroup.

PMID- 24035636
TI  - Genotype-phenotype spectrum of PYCR1-related autosomal recessive cutis laxa.
AB  - Autosomal recessive cutis laxa type 2B (ARCL2B; OMIM # 612940) is a segmental
      progeroid disorder caused by mutations in PYCR1 encoding pyrroline-5-carboxylate
      reductase 1, which is part of the conserved proline de novo synthesis pathway.
      Here we describe 33 patients with PYCR1-related ARCL from 27 families with
      initial diagnoses varying between wrinkly skin syndrome, gerodermia
      osteodysplastica, De Barsy syndrome or more severe progeria syndromes. Given the
      difficult differential diagnosis of ARCL syndromes we performed a systematic
      comparison of clinical features of PYCR1-related ARCL. Intrauterine growth
      retardation, a characteristic triangular facial gestalt, psychomotor retardation,
      and hypotonia were the most relevant distinctive hallmarks of ARCL due to proline
      de novo synthesis defects. Corneal clouding or cataracts, athetoid movements, and
      finger contractures were rather rare features, but had a high predictive value.
      In our cohort we identified 20 different PYCR1 mutations of which seven were
      novel. Most of the mutations accumulated in exons 4 to 6. Missense alterations of
      highly conserved residues were most frequent followed by splice site changes and
      a single nonsense mutation. Analysis of genotype-phenotype correlation revealed
      that patients with mutations in the first two exons had lower average clinical
      scores and absent or only mild intellectual disability. Structural analyses
      predicted interference with PYCR1 multimerization for a subset of missense
      mutations. These findings have implications for the clinics as well as the
      pathomechanism of PYCR1-related ARCL. 

PMID- 24035637
TI  - Correlation between CT-estimated tumor volume, pathologic tumor volume, and final
      pathologic specimen weight in children with Wilms' tumor.
AB  - OBJECTIVE: To evaluate the relationship of Wilms' tumor (WT) volume to weight,
      and evaluate computed tomography (CT) scan-derived final pathologic specimen
      weight estimation models. METHODS: We retrospectively reviewed WT patients from
      2003 to 2011 who had a pre-operative CT scan, final pathologic specimen weight,
      and tumor dimensions. A partial nephrectomy tumor cohort (n = 12) was used derive
      WT density. A radical nephrectomy cohort (n = 45) was used to develop a
      simplified estimation equation of final pathologic specimen weight, and analysis
      of all known estimation models was performed. RESULTS: Fifty-two patients were
      identified. WT volume and weight were not equivalent (p = 0.0410). WT density was
      1.3091 g/cm(3). WT volume and final pathologic specimen weight were not
      significant (p = 0.0007). Our model (p = 0.9983) and CT estimated ellipsoidal
      volume (p = 0.0741) were able to estimate final pathologic specimen weight in all
      tumors. However, CT-estimated ellipsoidal volume failed to estimate final
      pathologic specimen weight in specimens < 250 g (p = 0.0066). CONCLUSION:
      Pathologic WT volume is not equivalent to final pathologic specimen weight. Final
      pathologic specimen weight can be estimated from a pre-operative CT scan, which
      suggests that it may be used to improve pre-operative surgical planning and to
      reduce treatment morbidity.

PMID- 24035638
TI  - Long-term follow-up of transitional cell carcinoma of the bladder in childhood.
AB  - BACKGROUND: Bladder tumours are rare in children, with only 0.38% of cases
      occurring in the first two decades of life. OBJECTIVE: To describe a long-term
      follow-up series of nine urothelial bladder tumours in children. PATIENTS AND
      METHODS: We carried out a retrospective study covering the period from 1988 until
      2005. We found that during this time, urothelial tumours had been diagnosed at
      our centre in eight patients (9 tumours) younger than 18 years old who reported
      an episode of haematuria. Diagnosis was attained through renal and bladder
      ultrasound in 85% of patients, and through cystoscopy under anaesthesia in 15%.
      All cases were treated by means of transurethral resection of the bladder, with
      ensuing follow-up using renal and bladder ultrasound and urinary cytology.
      MEASUREMENTS: Patients characteristics and outcome are evaluated. RESULTS: Single
      exophytic tumours were present in seven (87.5%) of the patients, located either
      in the lateral wall or in the trigone; one patient showed two small tumours. The
      pathology was as follows: two G1Ta, one G1T1, one G2T1, and five G2Ta. There were
      no recurrences. CONCLUSIONS: Transitional cell carcinoma in childhood is of low
      grade and low aggressiveness. It has a good prognosis and recurrences are
      infrequent. We suggest performing a urinary cytology/cystoscopy every 6 months
      the first 2 years and urinary cytology/bladder ultrasound once a year.

PMID- 24035639
TI  - Pilot study of cognition in children with unilateral hearing loss.
AB  - OBJECTIVE: The objective of this study was to obtain preliminary data on the
      cognitive function of children with unilateral hearing loss in order to identify,
      quantify, and interpret differences in cognitive and language functions between
      children with unilateral hearing loss and with normal hearing. METHODS: Fourteen
      children ages 9-14 years old (7 with severe-to-profound sensorineural unilateral
      hearing loss and 7 sibling controls with normal hearing) were administered five
      tests that assessed cognitive functions of working memory, processing speed,
      attention, and phonological processing. RESULTS: Mean composite scores for
      phonological processing were significantly lower for the group with unilateral
      hearing loss than for controls on one composite and four subtests. The unilateral
      hearing loss group trended toward worse performance on one additional composite
      and on two additional phonological processing subtests. The unilateral hearing
      loss group also performed worse than the control group on the complex letter span
      task. Analysis examining performance on the two levels of task difficulty
      revealed a significant main effect of task difficulty and an interaction between
      task difficulty and group. CONCLUSIONS: Cognitive function and phonological
      processing test results suggest two related deficits associated with unilateral
      hearing loss: (1) reduced accuracy and efficiency associated with phonological
      processing, and (2) impaired executive control function when engaged in
      maintaining verbal information in the face of processing incoming, irrelevant
      verbal information. These results provide a possible explanation for the
      educational difficulties experienced by children with unilateral hearing loss.

PMID- 24035640
TI  - Nasal cavity dimensions in congenital pyriform aperture stenosis.
AB  - OBJECTIVE: To determine the dimensions of the nasal cavity in infants with
      congenital pyriform aperture stenosis (CPAS). STUDY DESIGN: The nasal cavities of
      seven children with CPAS were identified and were compared to the nasal cavities
      of 13 neonates (<30 days old) who had received CT scans for other indications.
      METHODS: The width of the nasal cavities was measured at the pyriform aperture,
      choana, and at two standardized points along the lateral nasal wall (LW-1 and LW
      2) between the pyriform aperture and choana. RESULTS: Comparison between neonates
      with and without CPAS demonstrates significant narrowing of the nasal cavity (not
      just the pyriform aperture) in infants with CPAS. Significantly smaller nasal
      width was noted at pyriform aperture, LW-1, and LW-2 (p<0.01, p<0.01, p=0.02). No
      significant narrowing was seen at the choana. CONCLUSION: These findings suggest
      that CPAS is associated with narrowing of the anterior 75% of the nasal cavity.
      This has implications for surgical management because simple pyriform aperture
      ostectomy may not be sufficient to relieve symptoms of obstruction.

PMID- 24035641
TI  - Interdisciplinary management of congenital infiltrating lipomatosis.
AB  - Congenital infiltrating lipomatosis is a benign yet locally invasive lipomatous
      tumor. Current treatment involves surgical excision and reconstruction of
      craniofacial deformity. Invasion of vital structures often makes complete
      resection problematic and recurrence is common. We present the case of a 15-year
      old female patient with extensive congenital infiltrating lipomatosis involving
      the left face. A broad treatment algorithm was devised involving surgical
      resection as well as targeted chemotherapy. At 18 month follow-up the patient
      demonstrated improved facial symmetry without evidence of disease progression.
      Combining surgical and medical intervention may allow for a synergistic approach
      to controlling this rare disease. 

PMID- 24035642
TI  - Acoustic properties of vocal singing in prelingually-deafened children with
      cochlear implants or hearing aids.
AB  - OBJECTIVE: The purpose of the present study was to investigate vocal singing
      performance of hearing-impaired children with cochlear implants (CI) and hearing
      aids (HA) as well as to evaluate the relationship between demographic factors of
      those hearing-impaired children and their singing ability. METHODS: Thirty-seven
      prelingually-deafened children with CIs and 31 prelingually-deafened children
      with HAs, and 37 normal-hearing (NH) children participated in the study. The
      fundamental frequencies (F0) of each note in the recorded songs were extracted
      and the duration of each sung note was measured. Five metrics were used to
      evaluate the pitch-related and rhythm-based aspects of singing accuracy. RESULTS:
      Children with CIs and HAs showed significantly poorer performance in either the
      pitch-based assessments or the rhythm-based measure than the NH children. No
      significant differences were seen between the CI and HA groups in all of these
      measures except for the mean deviation of the pitch intervals. For both hearing
      impaired groups, length of device use was significantly correlated with singing
      accuracy. CONCLUSIONS: There is a marked deficit in vocal singing ability either
      in pitch or rhythm accuracy in a majority of prelingually-deafened children who
      have received CIs or fitted with HAs. Although an increased length of device use
      might facilitate singing performance to some extent, the chance for the hearing
      impaired children fitted with either HAs or CIs to reach high proficiency in
      singing is quite slim.

PMID- 24035643
TI  - PID controller auto-tuning based on process step response and damping optimum
      criterion.
AB  - This paper presents a novel method of PID controller tuning suitable for higher
      order aperiodic processes and aimed at step response-based auto-tuning
      applications. The PID controller tuning is based on the identification of so
      called n-th order lag (PTn) process model and application of damping optimum
      criterion, thus facilitating straightforward algebraic rules for the adjustment
      of both the closed-loop response speed and damping. The PTn model identification
      is based on the process step response, wherein the PTn model parameters are
      evaluated in a novel manner from the process step response equivalent dead-time
      and lag time constant. The effectiveness of the proposed PTn model parameter
      estimation procedure and the related damping optimum-based PID controller auto
      tuning have been verified by means of extensive computer simulations. 

PMID- 24035646
TI  - Trends of karyotypical evolution in the pearl cichlid, Geophagus brasiliensis,
      from southern Brazil.
AB  - Chromosomal rearrangements such as inversions can facilitate speciation even in
      the presence of gene flow. The present study aims to analyze the karyotypic
      variation in six populations of Geophagus brasiliensis from southern Brazil. All
      specimens showed 2n=48 chromosomes, but three karyotypes were found to have one,
      two or three pairs of submetacentric chromosomes. Although G. brasiliensis did
      not exhibit variation in the diploid number, it presented a wide
      interpopulational variation mainly regarding the karyotype formula and specific
      chromosomal markers. Differences in the location of the major and minor rDNA loci
      were observed among the populations. Moreover, different patterns were observed
      in the distribution of the constitutive heterochromatin, presenting intra- and
      interpopulational variation. This supports the hypothesis that this taxon
      represents a complex species or that cryptic species are included in this group,
      indicating a possibleprocess of sympatric speciation. By potentially restricting
      gene flow between heterokaryotypes, the segregating chromosome rearrangements we
      describe for G. brasiliensis may play a role in diversification in this species
      complex.

PMID- 24035644
TI  - Cognitive processing therapy for veterans with comorbid PTSD and alcohol use
      disorders.
AB  - Posttraumatic stress disorder (PTSD) and alcohol-use disorders (AUD) frequently
      present comorbidity in veteran populations. Traditionally those with alcohol
      dependence have been excluded from PTSD treatment outcome studies, thus we do not
      know how those with alcohol dependence may tolerate or respond to PTSD-specific
      interventions; no studies to date have examined the extent to which cognitive
      PTSD interventions are tolerated or effective for those with comorbid PTSD/AUD.
      The present study examines the extent to which CPT is tolerated by and effective
      in treating PTSD symptoms for veterans with PTSD and AUD, as compared to veterans
      with PTSD only in an outpatient treatment setting. Data were obtained through
      chart review of 536 veterans diagnosed with PTSD who had received at least 1
      session of CPT at a Midwestern US Veterans Affairs hospital. Nearly half (n=264,
      49.3%) of the veterans in the study exhibited a current or past AUD diagnosis.
      Participants were grouped into the following diagnostic groups: current AUD (past
      12 months), past AUD (prior to 12 months), and no AUD. Participants completed an
      average of 9 sessions of CPT with no significant difference between AUD
      diagnostic groups on the number of CPT sessions completed. Individuals with past
      AUD had higher initial symptoms of self-reported PTSD symptoms than those with no
      AUD. All groups reported significant reductions in PTSD symptoms and depression
      over time. Overall, the results suggest that CPT appears well tolerated among
      veterans with comorbid AUD and is associated with significant reductions in
      symptoms of PTSD and depression in an outpatient treatment setting.

PMID- 24035647
TI  - The capacious hologenome.
AB  - Blending disciplines can be transformative in science, yet interdisciplinary
      mergers should not escape healthy skepticism. Indeed, the history of biology
      shows us that debates about the relative importance of nuclear genetics vs.
      microbial symbiosis in eukaryotic biology are among the most engaging. Today's
      technology may help resolve this century old debate as it illuminates the
      interwoven genomics and functions of symbionts with their host genome. Thus, we
      can now assert that all subdisciplines of zoology require microbiology. Although
      controversial to some, the evidence from studies of host-associated microbial
      communities indicates that metazoans are hologenomes - interconnected
      compositions of animal and microbes.

PMID- 24035645
TI  - Pharmacological treatment of comorbid PTSD and substance use disorder: recent
      progress.
AB  - Previous research has identified a strong association between posttraumatic
      stress disorder (PTSD) and substance use disorder (SUD), necessitating the
      development of treatments that address both conditions. Some pharmacotherapies
      are effective for the treatment of PTSD and SUD alone, however; no medications
      have been proven to be effective for the combination of these conditions. We
      review the recent advances in pharmacological treatment of comorbid PTSD and SUD.
      A randomized clinical trial of sertraline, a serotonin reuptake inhibitor (SSRI),
      did not show overall efficacy for comorbid PTSD and alcohol dependence (AD),
      although it may have efficacy among light drinkers. Another clinical trial
      demonstrated the efficacy of both disulfiram and naltrexone for the treatment of
      AD in individuals with PTSD. A more recent clinical trial suggested that
      norepinephrine uptake inhibitors may also have efficacy for the treatment of
      comorbid PTSD and AD. In animal and preliminary human studies, brain
      norepinephrine and glutamate/GABA have emerged as potential treatment targets for
      comorbid PTSD and SUD. Noradrenergic medications that are promising for comorbid
      PTSD and SUD include prazosin, guanfacine, and atomoxetine. Promising
      glutamate/GABA medications include topiramate, memantine, acamprosate, N
      acetylcysteine (NAC), and ketamine. The safety and efficacy of these medications
      for the treatment of PTSD and SUD need to be tested in controlled clinical
      trials. 

PMID- 24035648
TI  - Imported loiasis in France: a retrospective analysis of 47 cases.
AB  - BACKGROUND: French physicians occasionally encounter travelers (immigrants,
      expatriates, others) seeking care for loiasis. METHODS: We describe the clinical
      and biological patterns and treatment of 47 cases of imported loiasis seen at
      three French hospitals over a 15-year period (1998-2012). RESULTS: Most patients
      acquired their infection in Cameroon, Gabon, and Central African Republic.
      Overall, Calabar swellings were observed in 63% patients, and eye worm migration
      in 29%. Peripheral blood microfilariae were detected in 48% of patients and
      eosinophilia in 90% respectively. Calabar swellings and eosinophilia were more
      common among expatriates and travelers, whereas African immigrants were more
      likely to present with eye worm migration and have microfilaremia. First-line
      treatment was ivermectin in most cases (51%), followed by diethylcarbamazine
      (23%), albendazole (8%) or a combination of drugs (8%). Forty-one patients
      underwent clinical and parasitological follow-up for a mean period of 422 days
      [range 30-3600 days]. Clinical relapse and/or persistence/reappearance of blood
      microfilaria occurred in 10 patients. CONCLUSIONS: Clinical and biological
      features were comparable with the largest monocentric series of imported loiasis.
      There was a marked rate of failure after first-line treatment and rare adverse
      effects were reported. The treatment of patients with imported loiasis would
      benefit from standardization with guidelines for the choice of first and second
      line drugs, the length of follow-up and criteria for cure.

PMID- 24035649
TI  - Preoperative determination of ventriculostomy trajectory in ventriculoperitoneal
      shunt surgery using a simple modification of the standard coronal MRI.
AB  - The aim of this technical report is to report a new method for
      ventriculoperitoneal (VP) shunt placement by determining the angle and distance
      of the proximal shunt catheter trajectory in the coronal plane using a simple
      modification of a standard coronal MRI. A modified coronal MRI (mcMRI) was taken
      in the coronal plane, which included Kocher's point and a point 1cm anterior to
      the tragus. Using this mcMRI, the trajectory from Kocher's point to a target in
      the frontal horn may be determined, and the angle and distance of the proximal
      shunt catheter trajectory may also be obtained. We identified a "safety angle"
      for catheter insertion, which avoided contact with any intraventricular
      structures. In addition, the length of the proximal catheter was calculated using
      the mcMRI, which we defined as the "safety depth." Twenty VP shunt surgeries were
      performed using an individual safety angle and safety length as determined by a
      preoperative mcMRI. The ventriculostomy was successful on the first attempt in
      all patients. The accurate placement of the proximal catheter was confirmed using
      a postoperative mcMRI. Only one patient demonstrated a track hemorrhage around
      the catheter path on CT scans. Follow-up evaluations were performed 3 to 12
      months after the shunt surgery. The mcMRI protocol is a simple modification of
      the standard coronal MRI and may important for the determination of an accurate
      angle and distance of the proximal catheter during free-hand ventriculostomy for
      VP shunt.

PMID- 24035650
TI  - Memantine hydrochloride in the treatment of dementia subtypes.
AB  - Memantine hydrochloride is a first-line therapeutic drug approved by the US Food
      and Drug Administration for the management of moderate to severe Alzheimer's
      disease (AD). We conducted a review of the literature to determine the changes to
      the central glutamatergic neurotransmitter system in dementia subtypes and the
      available clinical evidence regarding the use of memantine in the treatment of
      different dementia subtypes. We conclude from our review that memantine may be an
      effective therapeutic option in managing AD, frontotemporal dementia, dementia
      with Lewy bodies, Parkinson's disease dementia and vascular dementia. When a
      diagnosis of the dementia subtype cannot be clearly identified or when there is
      no clear therapeutic option, memantine may be simple and safe. 

PMID- 24035651
TI  - Radiofrequency lesioning through deep brain stimulation electrodes: a pilot study
      of lesion geometry and temperature characteristics.
AB  - Deep brain stimulation (DBS) electrodes have been used effectively to perform
      radiofrequency lesions in the brain. This study aimed to characterize lesion
      geometry and peak tissue temperature achieved when lesioning through DBS
      electrodes. Fresh bovine liver was chosen for a medium as the tissue reliably
      changes color between 45 and 50  degrees C. Medtronic 3387 DBS electrodes
      (Medtronic Sofamor Danek, Inc., Memphis, TN, USA) and the Cosman G4
      Radiofrequency Generator (Cosman Medical, Inc., Burlington, MA, USA) were used
      for lesioning. Bipolar lesions were created at currents between 25 mA and 100 mA
      for 60-120 seconds. Peak tissue temperature was monitored with Cosman disposable
      cordotomy electrode (LCED; Cosman Medical Inc.) and recorded. Photographic
      analysis of the lesions was performed. Tissue impedance ranged between 800-900
      Ohms, and tissue temperature was maintained at 20  degrees C. With lesions at 25
      mA for up to 120 seconds, maximal tissue temperature achieved was 36  degrees C.
      This correlated with no visible lesions. At 50 mA, maximal tissue temperature
      exceeded 100  degrees C, which was associated with tissue charring. Lesions
      created at 35 mA and 40 mA led to an increase in tissue temperature of 63 
      degrees C and 75  degrees C, respectively. Lesion size was highly reproducible,
      increasing from 4.5 mm * 7 mm at 35 mA, to 6 mm * 7.5mm at 50 mA. Preliminary
      analysis suggests that caution should be exerted in using lesion amplitudes
      exceeding 40 mA (at 800 Ohms), as peak tissue temperatures in vivo could exceed
      100  degrees C. Further in vivo experiments with imaging correlates are needed to
      further test the safety of this technique.

PMID- 24035652
TI  - Malnutrition, anorexia and cachexia in cancer patients: A mini-review on
      pathogenesis and treatment.
AB  - Malnutrition, anorexia and cachexia are a common finding in cancer patients. They
      become more evident with tumor growth and spread. However, the mechanisms by
      which they are sustained often arise early in the history of cancer. For
      malnutrition, these mechanisms can involve primary tumor or damage by specific
      treatment such as anticancer therapies (surgery, chemotherapy, radiotherapy) also
      in cancers that usually are not directly responsible for nutritional and
      metabolic status alterations (i.e. bone tumors). For anorexia, meal-related
      neural or hormonal signals and humoral signals related to body fat or energy
      storage and the interaction of these signals with the hypothalamus or the
      hypothalamic inappropriate response play a pathogenetic role. Some cytokines are
      probably involved in these mechanisms. For cachexia, the production of
      proinflammatory cytokines by tumour cells is the initial mechanism; the main
      biochemical mechanisms involved include the ubiquitine proteasome-dependent
      proteolysis and heat shock proteins. Treatment includes pharmaceutical and
      nutritional interventions.

PMID- 24035653
TI  - Distal radius fracture metaphyseal comminution: a new radiographic parameter for
      quantifying, the metaphyseal collapse ratio (MCR).
AB  - INTRODUCTION: Metaphyseal comminution is widely considered as a key radiographic
      parameter that predicts fracture instability for distal radius fractures.
      However, no quantitative parameter is available to measure this degree of
      comminution. To quantify metaphyseal comminution objectively, the authors devised
      and validated the metaphyseal collapse ratio, a new radiographic index. MATERIALS
      AND METHODS: Seventy-four cases of distal radius fracture in the elderly were
      included in this analysis. After closed reduction, a strictly lateral plain
      radiograph was obtained and digitally adjusted. The metaphyseal collapse ratio
      (MCR) was calculated expressing the maximal radiolucent extent as a percentage of
      the intercortical distance. Furthermore, correlations between MCR and age,
      gender, DXA scores, and other radiographic parameters, namely, radial shortening,
      volar tilt, radial inclination, and the presence of an associated ulnar fracture
      were investigated. RESULTS: Mean metaphyseal collapse ratio in the cohort was
      calculated to be 51.7% by one observer and 53.7% by a second, showing good
      interobserver and mean intraobserver reliability (0.812, P<0.001 and 0.826,
      P<0.001, respectively). MCR was found to be significantly correlated with
      conventionally accepted radiographic parameters of fracture instability, that is,
      radial shortening (P<0.001), volar tilt (P<0.001), and radial inclination
      (P=0.002), but not with age, gender, DXA scores, and the presence of a combined
      ulnar fracture. CONCLUSIONS: Metaphyseal collapse ratio, a novel radiographic
      parameter, was found to provide a reliable measure of metaphyseal comminution,
      and to be significantly correlated with other radiographic parameters that
      predict distal radius fracture instability. LEVEL OF EVIDENCE: Level III,
      diagnostic.

PMID- 24035654
TI  - Unpredictability of hip behavior in Dyggve-Melchior-Clausen syndrome: a mid-term
      assessment of siblings.
AB  - Dyggve-Melchior-Clausen syndrome is a rare spondylo-epiphyseal disease, which
      almost constantly leads to both bilateral hip degeneration and dislocation. Few
      authors have reported to date the surgical management of this orthopaedic
      disorder. We present two new cases affecting siblings. One brother was treated by
      unilateral triple pelvic osteotomy combined with varus osteotomy of the proximal
      femur; the other was treated by bilateral Pemberton osteotomies with varus
      osteotomy of the proximal femur. At a respective 5-year and 3-year follow-up
      delay, both cases had evolved towards progressive subluxation recurrence along
      with severe hip degeneration. Based on both our experience and literature review,
      it seems that one should avoid operating these hips unless pain renders surgery
      mandatory. Total hip arthroplasty seems the only reliable surgical solution at
      the adult age and paediatric surgeons should keep in mind that previous femoral
      osteotomies will make it more challenging for adult orthopaedic surgeons to
      implant on a remodeled anatomy. 

PMID- 24035655
TI  - Modeling bromide effects on yields and speciation of dihaloacetonitriles formed
      in chlorinated drinking water.
AB  - This study examined effects of bromide on yields and speciation of
      dihaloacetonitrile (DHAN) species that included dichloro-, bromochloro- and
      dibromoacetonitriles generated in chlorinated water. Experimental data obtained
      using two water sources, varying concentrations and characters of Natural Organic
      Matter (NOM), bromide concentrations, reaction times, chlorine doses,
      temperatures and pHs were interpreted using a semi-phenomenological model that
      assumed the presence of three kinetically distinct sites in NOM (denoted as sites
      S1, S2 and S3) and the occurrence of sequential incorporation of bromine and
      chlorine into them. One site was found to react very fast with the chlorine and
      bromine but its contribution in the DHAN generation was very low. The site with
      the highest contribution to the yield of DHAN (>70%) has the lowest reaction
      rates. The model introduced dimensionless coefficients (denoted as phi1(DHAN),
      phi2(DHAN) and phi3(DHAN)) applicable to the initial DHAN generation sites and
      their monochlorinated and monobrominated products, respectively. These parameters
      were used to quantify the kinetic preference to bromine incorporation over that
      of chlorine. Values of these coefficients optimized for DHAN formation were
      indicative of the strongly preferential incorporation of bromine into the engaged
      NOM sites. The same set of phi(i)(DHAN) coefficients could be used to model the
      speciation of DHAN released from their kinetically different precursors. The
      dimensionless speciation coefficients phi(i)(DHAN) were determined to be site
      specific and dependent on the NOM content and character as well as pH. The
      presented model of DHAN formation and speciation can help quantify in more detail
      the generation of DHAN and provide more insight necessary for further assessment
      of their potential health effects.

PMID- 24035656
TI  - Itemizing the bundle: achieving and maintaining "zero" central line-associated
      bloodstream infection for over a year in a tertiary care hospital in Saudi
      Arabia.
AB  - BACKGROUND: "Zero" central line-associated bloodstream infections (CLABSI) have
      not been reported from Asian countries, which usually have predominance of
      difficult to curtail gram negative infections. It also remains unclear whether
      lowering CLABSI rates below National Healthcare Safety Network (NHSN) benchmarks
      in such countries is even possible. In this study, we evaluated effects of a
      quality improvement initiative to achieve "Zero CLABSI" in our intensive care
      unit. METHODS: A root cause analysis in February 2010 identified problems with
      clinical practice, environment, and products. Extensive education sessions were
      followed by implementation of strategies in the form of "itemized" bundles
      derived from practice guidelines, with complete enforcement starting August 2010.
      Results were benchmarked against NHSN data. Data were analyzed in a
      preintervention (1 year) and postintervention (2 years) fashion, using Poisson
      regression analysis to generate incidence-rate ratio (IRR). RESULTS: In the
      preintervention period, CLABSI rate was 6.9/1,000 catheter-days (CDs) (35
      CLABSI/5,083 CDs). In the postintervention year 1, rate was 1.06/1,000 CDs (4
      CLABSI/3,787 CDs) with IRR of 0.15 (95% confidence interval: 0.04-0.44, P < .001)
      and reduction of 85%. In postintervention year 2, rate was 0.35/1,000 CDs
      (1/2,860 CDs) with IRR of 0.05 (95% confidence interval: 0.001-0.31, P < .001).
      There was a period of "Zero CLABSI" for 15 consecutive months, surpassing NHSN
      benchmarks. CONCLUSION: CLABSIs can be eliminated in any intensive care unit
      regardless of the location and type of organism. NHSN data should be a realistic
      CLABSI benchmarking target for developing countries.

PMID- 24035657
TI  - "Recognizing rapport": health professionals' lived experience of caring for
      patients under transmission-based precautions in an Australian health care
      setting.
AB  - BACKGROUND: Preventing health care-associated infections is essential to the
      safety and quality of health care. Although patients' experience of care under
      isolation is well established, little is known of health care workers'
      experiences when providing such care. This study explored the health
      professionals; lived experience of caring for patients under transmission-based
      precautions. METHODS: Interpretive phenomenology was used to examine 12 health
      care professionals' lived experience of providing care under transmission-based
      precautions in 3 health care facilities in Australia. Data were obtained from in
      depth interviews and observations of health professionals. FINDINGS: The
      essential phenomena of "recognizing rapport" represented the health
      professionals' lived experience. Three themes emerged starting with (1)
      relationships with others, their rapport and communication with patients,
      patients' families and visitors, and colleagues. These relationships are
      influenced by (2) barriers to practice, such as personal level of comfort when
      wearing personal protective equipment, physical limitations of the environment,
      and management of workload and resources. Such barriers influence (3) patient
      outcomes, namely the quality of the care provided and adverse events. CONCLUSION:
      In the context of caring for patients under transmission-based precautions, the
      relationships between health professionals and their patients are critical to the
      quality and safety of health care with respect to infection prevention and
      control.

PMID- 24035658
TI  - Transdiaphragmatic extrapericardial approach of the inferior vena cava.

PMID- 24035659
TI  - Factors associated with rapid progression to esophagectomy for benign disease.
AB  - BACKGROUND: The reasons why some patients with benign esophageal diseases require
      esophagectomy remain poorly understood. In this study we sought to define the
      rate of progression to esophagectomy and the postesophagectomy outcomes of
      patients with benign esophageal conditions in whom 1 or more previous
      interventions failed. STUDY DESIGN: Using a prospective database, we
      retrospectively identified patients who had esophagectomies for benign disease
      between 1978 and 2010. Patients who underwent 1 or more esophageal interventions
      before resection met inclusion criteria. We examined factors associated with
      progression to esophagectomy and with postesophagectomy complications. RESULTS:
      One hundred eleven patients underwent 1 or more esophageal interventions before
      esophagectomy. The most common indications for initial intervention were
      achalasia (37%, n = 41) and gastroesophageal reflux (33%, n = 37). More rapid
      progression to esophagectomy was associated with acquired esophageal disease (p <
      0.01), initial esophageal intervention at age >= 18 (p < 0.01), and previous
      fundoplication (p = 0.03). Complications of esophagectomy included 30-day
      mortality (n = 2, 1%), chylothorax (n = 4, 3%), anastomotic leak (n = 17, 11%),
      and reoperation (n = 17, 11%). CONCLUSIONS: These findings highlight the
      importance of increased awareness of the potential progression to esophagectomy
      during repeated procedural interventions for benign esophageal disease. A subset
      of the patients who progress more rapidly, including adult patients and those
      with acquired disease and/or previous fundoplication, may benefit from counseling
      about potential esophagectomy.

PMID- 24035660
TI  - Baseline subtraction technique in the frequency-wavenumber domain for high
      sensitivity damage detection.
AB  - This paper suggests a method for high-sensitivity damage detection. The method is
      based on pitch-catch measurements of Lamb waves combined with a baseline
      subtraction technique in the frequency-wavenumber domain. Small amplitude
      converted modes, generated during the interaction of propagating waves with
      damage, can thus be detected with minimal a priori information regarding their
      expected location in the frequency-wavenumber plane. This method is applied in
      the present paper to a case of notches with varied depth. Finite element
      simulations are carried out in the temporal domain to mimic results obtainable in
      real-world experiments. Two cases are studied, namely when each of the two pure
      fundamental modes are incident on a notch. The advantages of the method are
      detailed. The procedure to implement this method is described in the context of
      Structural Health Monitoring (SHM) or Non-Destructive Testing (NDT). 

PMID- 24035661
TI  - The complexity of chloroplast chaperonins.
AB  - Type I chaperonins are large oligomeric protein ensembles that are involved in
      the folding and assembly of other proteins. Chloroplast chaperonins and co
      chaperonins exist in multiple copies of two distinct isoforms that can combine to
      form a range of labile oligomeric structures. This complex system increases the
      potential number of chaperonin substrates and possibilities for regulation. The
      incorporation of unique subunits into the oligomer can modify substrate
      specificity. Some subunits are upregulated in response to heat shock and some
      show organ-specific expression, whereas others possess additional functions that
      are unrelated to their role in protein folding. Accumulating evidence suggests
      that specific subunits have distinct roles in biogenesis of ribulose-1,5
      bisphosphate carboxylase oxygenase (Rubisco). 

PMID- 24035663
TI  - [Acute progressive disseminated histoplasmosis in a young immunocompetent
      patient].

PMID- 24035662
TI  - The Computer Book of the Internal Medicine Resident: competence acquisition and
      achievement of learning objectives.
AB  - BACKGROUND: The Computer Book of the Internal Medicine resident (CBIMR) is a
      computer program that was validated to analyze the acquisition of competences in
      teams of Internal Medicine residents. OBJECTIVES: To analyze the characteristics
      of the rotations during the Internal Medicine residency and to identify the
      variables associated with the acquisition of clinical and communication skills,
      the achievement of learning objectives and resident satisfaction. METHODS: All
      residents of our service (n=20) participated in the study during a period of 40
      months. The CBIMR consisted of 22 self-assessment questionnaires specific for
      each rotation, with items on services (clinical workload, disease
      protocolization, resident responsibilities, learning environment, service
      organization and teamwork) and items on educational outcomes (acquisition of
      clinical and communication skills, achievement of learning objectives, overall
      satisfaction). Associations between services features and learning outcomes were
      analyzed using bivariate and multivariate analysis. RESULTS: An intense clinical
      workload, high resident responsibilities and disease protocolization were
      associated with the acquisition of clinical skills. High clinical competence and
      teamwork were both associated with better communication skills. Finally, an
      adequate learning environment was associated with increased clinical competence,
      the achievement of educational goals and resident satisfaction. CONCLUSIONS:
      Potentially modifiable variables related with the operation of clinical services
      had a significant impact on the acquisition of clinical and communication skills,
      the achievement of educational goals, and resident satisfaction during the
      specialized training in Internal Medicine.

PMID- 24035665
TI  - [Fever and Brugada syndrome].

PMID- 24035666
TI  - Cryptogenia multifocal ulcerous stenosing enteritis: an entity on its own as a
      cause of abdominal pain, iron deficiency anemia and protein-losing enteropathy.
AB  - We studied a patient with edema secondary to protein losing enteropathy, and
      recurrent bouts of bloating and abdominal pain secondary to intestinal
      subocclusion episodes. After the clinical study, the patient was diagnosed of
      cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), that is a rare
      disease, probably caused by mutations in the gene PLA2G4A, and characterized by
      multiple short stenosis of the small bowel with superficial ulcers, which do not
      exceed the submucosa layer. Inflammatory bowel disease (Chron's disease),
      intestinal tuberculosis and intestinal ulcers secondary to non-steroidal anti
      inflammatory drugs are the main differential diagnosis. To sum up, physicians
      should included CMUSE in the differential diagnosis of recurrent abdominal pain,
      iron deficiency anaemia, occult intestinal bleeding, edema and protein losing
      enteropathy. 

PMID- 24035667
TI  - [Pain, edema and cyanosis of the lower limbs].

PMID- 24035668
TI  - Role of the extensor carpi ulnaris in the stabilization of the lunotriquetral
      joint. An experimental study.
AB  - STUDY DESIGN: Experimental laboratory-based research in biomechanics.
      INTRODUCTION: The mechanisms by which some lunotriquetral (LTq) ligament
      disruptions remain stable are not known. PURPOSE OF THE STUDY: To investigate the
      contribution of muscles in preventing carpal destabilization when the LTq
      ligaments are torn. METHODS: Ten fresh cadaver wrists, set vertical in a jig,
      were isometrically loaded through five wrist motor tendons. Changes in carpal
      alignment secondary to the application of loads were monitored by a FastrakTM
      electromagnetic motion tracking device, before and after sectioning the LTq
      ligaments. RESULTS: After LTq ligaments sectioning, wrist loading forced the
      triquetrum into flexion (5.4 degrees  average) and supination (2.9 ). The only
      muscle capable of extending and pronating the collapsed triquetrum was the
      extensor carpi ulnaris (ECU). CONCLUSIONS: Inadequate ECU muscle function is an
      important destabilizing factor in LTq deficient wrists. Dynamic LTq instabilities
      may benefit from proprioceptionally training the ECU muscle, while avoiding
      carpal supination torques.

PMID- 24035669
TI  - Are YouTube seizure videos misleading? Neurologists do not always agree.
AB  - The internet has become the first stop for the public and patients to seek health
      related information. Video-sharing websites are particularly important sources of
      information for those seeking answers about seizures and epilepsy. Because of the
      widespread popularity of YouTube, we sought to explore whether a seizure
      diagnosis and classification could reliably be applied. All videos related to
      "seizures" were reviewed, and irrelevant videos were excluded. The remaining 162
      nonduplicate videos were analyzed by 4 independent pediatric neurologists who
      classified the events as epilepsy seizures, nonepileptic seizures, or
      indeterminate. Videos designated as epilepsy seizures were then classified into
      focal, generalized, or unclassified. At least 3 of the 4 reviewers agreed that
      35% of the videos showed that the events were "epilepsy seizures", at least 3 of
      the 4 reviewers agreed that 28% of the videos demonstrated that the events were
      "nonepileptic seizures", and there was good agreement that 7% of the videos
      showed that the event was "indeterminate". Overall, interrater agreement was
      moderate at k=0.57 for epilepsy seizures and k=0.43 for nonepileptic seizures.
      For seizure classification, reviewer agreement was greatest for "generalized
      seizures" (k=0.45) and intermediate for "focal seizures" (k=0.27), and there was
      no agreement for unclassified events (k=0.026, p=0.2). Overall, neurology
      reviewer agreement suggests that only approximately one-third of the videos
      designated as "seizures" on the most popular video-sharing website, YouTube,
      definitely depict a seizure. Caution should be exercised in the use of such
      online video media for accessing educational or self-diagnosis aids for seizures.

PMID- 24035670
TI  - Effect of nature-based sound therapy on agitation and anxiety in coronary artery
      bypass graft patients during the weaning of mechanical ventilation: A randomised
      clinical trial.
AB  - BACKGROUND: Weaning from mechanical ventilation is a frequent nursing activity in
      critical care. Nature-based sound as a non-pharmacological and nursing
      intervention effective in other contexts may be an efficient approach to
      alleviating anxiety, agitation and adverse effects of sedative medication in
      patients undergoing weaning from mechanical ventilation. OBJECTIVES: This study
      identified the effect of nature-based sound therapy on agitation and anxiety on
      coronary artery bypass graft patients during weaning from mechanical ventilation.
      METHODS: A randomised clinical trial design was used. 120 coronary artery bypass
      graft patients aged 45-65 years undergoing weaning from mechanical ventilation
      were randomly assigned to intervention and control groups. Patients in the
      intervention group listened to nature-based sounds through headphones; the
      control group had headphones with no sound. Haemodynamic variables, anxiety
      levels and agitation were assessed using the Faces Anxiety Scale and Richmond
      Agitation Sedation Scale, respectively. Patients in both groups had vital signs
      recorded after the first trigger, at 20 min intervals throughout the procedure,
      immediately after the procedure, 20 min after extubation, and 30 min after
      extubation. Data were collected over 5 months from December 2012 to April 2013.
      RESULTS: The intervention group had significantly lower anxiety and agitation
      levels than the control group. Regarding haemodynamic variables, a significant
      time trend and interaction was reported between time and group (p<0.001). A
      significant difference was also found between the anxiety (p<0.002) and agitation
      (p<0.001) scores in two groups. CONCLUSIONS: Nature-based sound can provide an
      effective method of decreasing potential adverse haemodynamic responses arising
      from anxiety and agitation in weaning from mechanical ventilation in coronary
      artery bypass graft patients. Nurses can incorporate this intervention as a non
      pharmacological intervention into the daily care of patients undergoing weaning
      from mechanical ventilation in order to reduce their anxiety and agitation.

PMID- 24035671
TI  - Neutral to positive views on the consequences of nurse prescribing: Results of a
      national survey among registered nurses, nurse specialists and physicians.
AB  - BACKGROUND: Over the last two decades, the number of countries where nurses are
      legally permitted to prescribe medication has grown considerably. A lack of peer
      support and/or objections by physicians can act as factors hampering nurse
      prescribing. Earlier research suggests that physicians are generally less
      supportive and more concerned about nurse prescribing than nurses are. However,
      direct comparisons between doctors' and nurses' views are scarce and are often
      based on small sample sizes. OBJECTIVES: To gain insight into the views of Dutch
      registered nurses (RNs), nurse specialists (with a master's in Advanced Nursing
      Practice) and physicians on the consequences of nurse prescribing. DESIGN: Survey
      study. PARTICIPANTS: Survey questionnaires were sent to national samples of RNs,
      nurse specialists and physicians. METHODS: The questionnaire addressed, among
      others, respondents' general views on the consequences of nurse prescribing for
      the quality of care, the nursing and medical professions, and the relationship
      between the medical and nursing professions. RESULTS: The net response rate was
      66.0% for RNs (n=617), 28.3% for nurse specialists (n=375) and 33.7% for
      physicians (n=265). It was found that all groups agreed that nurse prescribing
      benefits nurses' daily practice and the nursing profession. There were few
      concerns about negative consequences for physicians' practice and the medical
      profession. Nurse specialists gave significantly (P<0.05) more positive scores on
      most items than RNs and physicians. We found relatively little difference in
      views between RNs and physicians. It was only on issues surrounding the quality
      of care and patient safety that doctors showed more concerns, albeit mild, than
      RNs and nurse specialists. CONCLUSIONS: RNs, nurse specialists and physicians
      generally hold neutral to moderately positive views on nurse prescribing. This is
      beneficial for the implementation and potential success of nurse prescribing in
      practice, as a lack of peer support and/or objections from physicians can be a
      hampering factor. However, concerns about the consequences of nurse prescribing
      for the quality of care and patient safety remain a point for attention,
      especially among physicians.

PMID- 24035672
TI  - Prolactin response to buspirone is not impaired in drug-naive first episode
      patients with major depressive disorder.
AB  - BACKGROUND: An altered postsynaptic 5-HT1A receptor function along with
      hypercortisolemia has been associated with major depressive disorder (MDD).
      However, several methodological considerations related to data interpretation
      arise when subjects previously exposed to psychotropic medication are included in
      the study population. To address those issues we designed a study in a well
      defined cohort of first-episode, treatment-naive MDD patients. METHODS: This
      cross-sectional case-control pharmacologic challenge study was designed to
      investigate the prolactin (PRL) response to buspirone in 21 non-late-life adult,
      treatment-naive MDD patients with the first affective episode and in 20 age- and
      sex-matched healthy controls. Depressed patients showed a basal score in the
      Hamilton Rating Scale for Depression (HAMD-17) higher than 20. RESULTS: No
      significant difference in PRL response to buspirone between first-episode,
      treatment-naive patients with MDD and controls, was observed. The correlation
      between basal cortisol levels and PRL response was not observed in MDD group
      while significant negative correlation was found in healthy controls. The
      significantly higher PRL response to buspirone was observed in melancholic
      patients as compared to non-melancholic subjects. LIMITATIONS: The current study
      is limited by its cross-sectional design, small sample size, factors related to
      neuroendocrine challenge methodology, and no placebo control. CONCLUSION: These
      results indicate no consistent changes in the hormonal response to the 5-HT1A
      agonist buspirone in major depression. Taken into account the interpretation of
      the buspirone test the present study does not support the hypothesis of an
      altered functional activity with down-regulation of the postsynaptic 5-HT1A
      receptor and/or in the postsynaptic receptor signal transduction in the
      hypothalamus in the pathogenesis of MDD.

PMID- 24035673
TI  - Randomised controlled non-inferiority trial with 3-year follow-up of internet
      delivered versus face-to-face group cognitive behavioural therapy for depression.
AB  - BACKGROUND: Guided internet-delivered cognitive behaviour therapy (ICBT) has been
      found to be effective in the treatment of mild to moderate depression, but there
      have been no direct comparisons with the more established group-based CBT with a
      long-term follow-up. METHOD: Participants with mild to moderate depression were
      recruited from the general population and randomized to either guided ICBT (n=33)
      or to live group treatment (n=36). Measures were completed before and after the
      intervention to assess depression, anxiety, and quality of life. Follow-ups were
      conducted at one-year and three-year after the treatment had ended. RESULTS: Data
      were analysed on an intention-to-treat basis using linear mixed-effects
      regression analysis. Results on the self-rated version of the Montgomery-Asberg
      Depression Scale showed significant improvements in both groups across time
      indicating non-inferiority of guided ICBT, and there was even a tendency for the
      guided ICBT group to be superior to group-based CBT at three year follow-up.
      Within-group effect sizes for the ICBT condition at post-treatment showed a
      Cohen's d=1.46, with a similar large effect at 3-year follow-up, d=1.78. For the
      group CBT the corresponding within-group effects were d=0.99 and d=1.34,
      respectively. LIMITATIONS: The study was small with two active treatments and
      there was no placebo or credible control condition. CONCLUSIONS: Guided ICBT is
      at least as effective as group-based CBT and long-term effects can be sustained
      up to 3 years after treatment.

PMID- 24035674
TI  - Multicomponent phytotherapeutic approach gaining momentum: Is the "one drug to
      fit all" model breaking down?
AB  - Natural product based drugs constitute a substantial proportion of the
      pharmaceutical market particularly in the therapeutic areas of infectious
      diseases and oncology. The primary focus of any drug development program so far
      has been to design selective ligands (drugs) that act on single selective disease
      targets to obtain highly efficacious and safe drugs with minimal side effects.
      Although this approach has been successful for many diseases, yet there is a
      significant decline in the number of new drug candidates being introduced into
      clinical practice over the past few decades. This serious innovation deficit that
      the pharmaceutical industries are facing is due primarily to the post-marketing
      failures of blockbuster drugs. Many analysts believe that the current capital
      intensive model-"the one drug to fit all" approach will be unsustainable in
      future and that a new "less investment, more drugs" model is necessary for
      further scientific growth. It is now well established that many diseases are
      multi-factorial in nature and that cellular pathways operate more like webs than
      highways. There are often multiple ways or alternate routes that may be switched
      on in response to the inhibition of a specific target. This gives rise to the
      resistant cells or resistant organisms under the specific pressure of a targeted
      agent, resulting in drug resistance and clinical failure of the drug. Drugs
      designed to act against individual molecular targets cannot usually combat
      multifactorial diseases like cancer, or diseases that affect multiple tissues or
      cell types such as diabetes and immunoinflammatory diseases. Combination drugs
      that affect multiple targets simultaneously are better at controlling complex
      disease systems and are less prone to drug resistance. This multicomponent
      therapy forms the basis of phytotherapy or phytomedicine where the holistic
      therapeutic effect arises as a result of complex positive (synergistic) or
      negative (antagonistic) interactions between different components of a cocktail.
      In this approach, multicomponent therapy is considered to be advantageous for
      multifactorial diseases, instead of a "magic bullet" the metaphor of a "herbal
      shotgun" might better explain the state of affairs. The different interactions
      between various components might involve the protection of an active substance
      from decomposition by enzymes, modification of transport across membranes of
      cells or organelles, evasion of multidrug resistance mechanisms among others. 

PMID- 24035675
TI  - Computational methods for drug design and discovery: focus on China.
AB  - In the past decades, China's computational drug design and discovery research has
      experienced fast development through various novel methodologies. Application of
      these methods spans a wide range, from drug target identification to hit
      discovery and lead optimization. In this review, we firstly provide an overview
      of China's status in this field and briefly analyze the possible reasons for this
      rapid advancement. The methodology development is then outlined. For each
      selected method, a short background precedes an assessment of the method with
      respect to the needs of drug discovery, and, in particular, work from China is
      highlighted. Furthermore, several successful applications of these methods are
      illustrated. Finally, we conclude with a discussion of current major challenges
      and future directions of the field. 

PMID- 24035676
TI  - Comparative effect of simulated solar light, UV, UV/H2O2 and photo-Fenton
      treatment (UV-Vis/H2O2/Fe2+,3+) in the Escherichia coli inactivation in
      artificial seawater.
AB  - Innovative disinfection technologies are being studied for seawater, seeking a
      viable alternative to chlorination. This study proposes the use of H2O2/UV254 and
      photo-Fenton as disinfection treatment in seawater. The irradiations were carried
      out using a sunlight simulator (Suntest) and a cylindrical UV reactor. The
      efficiency of the treatment was compared for Milli-Q water, Leman Lake water and
      artificial seawater. The presence of bicarbonates and organic matter was
      investigated in order to evaluate possible effects on the photo-Fenton
      disinfection treatment. The photo-Fenton treatment, employing 1 mg L(-1) Fe(2+)
      and 10 mg L(-1) of H2O2, led to the fastest bacterial inactivation kinetics.
      Using H2O2/UV254 high disinfection rates were obtained similar to those obtained
      with photo-Fenton under UV254 light. In Milli-Q water, the rate of inactivation
      for Escherichia coli was higher than in Leman Lake water and seawater due to the
      lack of inorganic ions affecting negatively bacteria inactivation. The presence
      of bicarbonate showed scavenging of the OH(*) radicals generated in the treatment
      of photo-Fenton and H2O2/UV254. Despite the negative effect of inorganic ions,
      especially HCO3(-), the disinfection treatments with AOPs in lake water and
      seawater improved significantly the disinfection compared to light alone
      (simulated sunlight and UV254). In the treatment of photo-Fenton with simulated
      sunlight, dissolved organic matter had a beneficial effect by increasing the rate
      of inactivation. This is associated with the formation of Fe(3+)-organo
      photosensitive complexes leading to the formation of ROS able to inactivate
      bacteria. This effect was not observed in the photo-Fenton with UV254. Growth of
      E. coli surviving in seawater was observed 24 and 48 h after treatment with UV
      light. However, growth of surviving bacteria was not detected after photo-Fenton
      with UV254 and H2O2/UV254 treatments. This study suggests H2O2/UV254 and photo
      Fenton treatments for the disinfection of seawater, in spite its high
      concentration of salts.

PMID- 24035677
TI  - Iron anode mediated transformation of selenate in sand columns.
AB  - Removal of aqueous selenate by iron electrolysis is investigated using sand
      packed column experiments under a flowing condition. An iron anode generates
      ferrous ions, while cathode produces hydroxide, thus producing ferrous hydroxide
      capable of reducing selenate to elemental selenium. Additionally, siderite could
      reduce selenate or selenite to elemental selenium. The removal rate of selenate
      is proportional to the contact time and the yield of ferrous hydroxide or ferrous
      carbonate. At a sequence of anode-cathode, the transformation of selenate mostly
      occurs in the zone after cathode. An operation of 48 h electrolysis finally
      transforms 82.2% of selenate at 0.2 mM of initial concentration, 1.8 m/day of
      seepage velocity and 1.26 mA/cm(2) of current density. A longer reactive zone
      after cathode slightly increases the reduction of selenate to 84.1%, in
      comparison with 82.2% of a shorter residence time in the reactive zone after
      cathode. With shorter electrode spacing (approximately 27% shorter), the
      transformation rate of selenate decreased to 73.5%; however, the specific
      electrical energy consumption was saved by 78%. A sequence of cathode-anode was
      ineffective in removing selenate because of the lack of reducing agent in the
      column. The results indicate that the electrochemical system might be effective
      in removing selenate in a single well.

PMID- 24035678
TI  - Enhanced detection of nanostructures by scanning electron microscopy using
      insulating materials.
AB  - We report a simple method by which 1D conducting structures with sub-micron
      diameters can be detected in a scanning electron microscope at magnifications
      more than an order of magnitude less than would be expected for their size. This
      enhanced detection was possible under normal operating conditions using a
      standard secondary electron detector. The technique requires only that the 1D
      samples must be in good physical contact with an insulating material. Normally,
      the insulating materials become charged upon electron beam exposure, making them
      appear relatively bright when imaged by the electron microscope. However, the
      insulating material appears relatively dark in the vicinity surrounding the
      conducting 1D structures. This darkened halo can be over 50 times wider than the
      diameter of the 1D structure itself, making it easy to detect at relatively low
      magnifications. This dark halo is due to the dissipation of charge from the
      surface of the conducting material into the conducting nanostructure. Thus, this
      technique can enable the rapid detection of very small, conducting 1D particles
      at very low magnification levels, and is simple enough to enable a rapid assaying
      of samples for the existence of sub-micron 1D structures. 

PMID- 24035679
TI  - Multivariate statistical analysis as a tool for the segmentation of 3D spectral
      data.
AB  - Acquisition of three-dimensional (3D) spectral data is nowadays common using many
      different microanalytical techniques. In order to proceed to the 3D
      reconstruction, data processing is necessary not only to deal with noisy
      acquisitions but also to segment the data in term of chemical composition. In
      this article, we demonstrate the value of multivariate statistical analysis (MSA)
      methods for this purpose, allowing fast and reliable results. Using scanning
      electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) coupled
      with a focused ion beam (FIB), a stack of spectrum images have been acquired on a
      sample produced by laser welding of a nickel-titanium wire and a stainless steel
      wire presenting a complex microstructure. These data have been analyzed using
      principal component analysis (PCA) and factor rotations. PCA allows to
      significantly improve the overall quality of the data, but produces abstract
      components. Here it is shown that rotated components can be used without prior
      knowledge of the sample to help the interpretation of the data, obtaining quickly
      qualitative mappings representative of elements or compounds found in the
      material. Such abundance maps can then be used to plot scatter diagrams and
      interactively identify the different domains in presence by defining clusters of
      voxels having similar compositions. Identified voxels are advantageously overlaid
      on secondary electron (SE) images with higher resolution in order to refine the
      segmentation. The 3D reconstruction can then be performed using available
      commercial softwares on the basis of the provided segmentation. To asses the
      quality of the segmentation, the results have been compared to an EDX
      quantification performed on the same data. 

PMID- 24035680
TI  - Comprehensive mutation analysis of the TERT promoter in bladder cancer and
      detection of mutations in voided urine.

PMID- 24035681
TI  - Mini-slings for female urinary stress incontinence: a promising option, but what
      comes later is not always progress.

PMID- 24035682
TI  - Endogenous pararetroviruses--a reservoir of virus infection in plants.
AB  - Endogenous pararetrovirus sequences (EPRV) belonging to the plant virus family
      Caulimoviridae have been discovered in the genomes of a wide range of
      Angiosperms. Although knowledge of EPRVs in plants is still in its infancy, it
      has been shown clearly in three different plant-virus pathosystems that these
      integrations are capable of generating functional circular viral genomes, and can
      thus trigger systemic infection. Here, we recapitulate information gathered over
      the last 15 years on how EPRVs contribute to virus replication in plants. We
      first present recent advances in our understanding of the molecular mechanisms
      involved in the transition from integrated to circular viral forms before
      addressing how EPRVs are controlled in planta. 

PMID- 24035683
TI  - Successes and challenges in the antiviral field.

PMID- 24035684
TI  - [Rupture by attrition of the median nerve found during a carpal tunnel release
      procedure].
AB  - We report the finding of a subtotal rupture of the median nerve caused by a
      "bridge" or"easel" erosion due to a sequela of childhood wrist fracture. This
      unpublished observation was made during a carpal tunnel release procedure on an
      80-year-old patient who was operated on for recurrence of a severe carpal tunnel
      syndrome 30 years after a previous neurolysis. If the flexor tendon ruptures are
      widely described, as well as nerve sections following high energy trauma, the
      median nerve rupture caused by its erosion over a bony projection has never been
      published at the best of our knowledge. 

PMID- 24035685
TI  - [Autologous fat grafting in the surgical management of painful scar: preliminary
      results].
AB  - The purpose of this study was to report our experience about the effectiveness of
      autologous fat injections in the management of painful scars. Between 2010 and
      2012, all patients with persistent incisional pain despite a well-conduced 6
      months medical treatment received an autologous fat graft according to the
      technique originally described by Coleman. Results interpretation was based on
      pain improvement thanks to a Visual Analogic Scale (VAS), postoperative patient
      satisfaction, reduction on analgesics intake and quality of life improvement.
      Eleven patients were included, the mean quantity of fat injected was 11cm(3).
      Nine patients (1.5%) benefited from a complete or significant pain decrease,
      74.5% reported being very satisfied or satisfied with the result. The mean
      reduction of VAS was 3.5 points. We did not observe any complication. Autologous
      fat grafting is an innovative therapeutic approach and appears to be an
      attractive concept in the management of scar neuromas resistant to drug
      treatment, by providing an easy effective and safe surgical treatment. 

PMID- 24035686
TI  - Cervical rib resulting in amaurosis fugax and stroke.

PMID- 24035687
TI  - The possible influence of varying diameter of aligned electrospun fibers on
      Schwann cells maturation in culture.
AB  - The development of Schwann cells, the principal glial cell in the peripheral
      nervous system, occurs through a series of transitional embryonic and postnatal
      phases, which are tightly regulated by a number of axonal signals. During the
      axon ensheathment and myelin growth, the diameter of the axon play an important
      role in the maturation of Schwann cells. Because of electrospun fibers similar to
      protein fibers within the native extracellular matrix, the scaffolds are being
      developed as neural tissue engineering scaffolds. Until now, the correlation
      between varying diameter of aligned electrospun fibers and Schwann cells
      maturation has not been investigated. We hypothesize that the different diameter
      of aligned electrospun fibers may influence the maturation of Schwann cells and
      may help improve the outcome of cell-based approaches to cure demyelinated
      lesions or peripheral nerve regeneration. 

PMID- 24035688
TI  - Leptin as a neuroprotective agent in glaucoma.
AB  - Glaucoma is a disease characterized by progressive optic nerve degeneration and
      is the leading cause of irreversible blindness worldwide. More than 60 million
      people globally are affected by glaucoma, of which 8 million people suffer from
      bilateral blindness, making glaucoma the second leading cause of bilateral
      blindness worldwide. Current management of glaucoma is aimed at reducing
      intraocular pressure via a number of different strategies. Current treatments do
      not attempt to correct the underlying pathology of glaucoma, which is the cell
      degeneration and ultimate death of retinal ganglion cells, thereby limiting their
      clinical efficacy. A neuroprotective approach to glaucoma management would
      address the underlying pathology and would, in theory, be beneficial to all
      patients regardless of risk and causative factors. Here it is proposed that
      leptin could be used as a potential neuroprotective agent in the management of
      glaucoma. Leptin has shown neuroprotective promise in a number of
      neurodegenerative diseases, and there has been increasing evidence that
      glaucomatous neurodegeneration is analogous to other neurodegenerative diseases
      in the central nervous system. Leptin could target retinal ganglion cell death by
      a number of mechanisms, namely apoptosis, oxidative stress and excitotoxicity
      reduction. This article presents evidence linking current understanding about
      leptin's neuroprotective effect and the molecular mechanisms underlying glaucoma.

PMID- 24035689
TI  - Challenging the clinical relevance of folinic acid over rescue after high dose
      methotrexate (HDMTX).
AB  - THE HYPOTHESIS: The use of adequate folinic acid rescue (in clinically relevant
      doses) after high dose methotrexate will prevent neurotoxicity without reducing
      treatment results. METHODS: A literature search was performed to test the
      hypothesis that no evidence for the existence of folinic acid over-rescue of high
      dose methotrexate (MTX) in clinically relevant situations exists (evidence that
      too much folinic acid reduced cure rate). EMPIRICAL DATA: Examples of folinic
      acid over-rescue after lower doses of MTX were found and has been cited as
      evidence of over rescue of high dose MTX. Mega doses of folinic acid, used when
      toxic levels of MTX occurred, also could neutralize the MTX effect. Data were
      found to support the contention that higher levels of MTX require
      disproportionally higher folinic acid doses for rescue. Careful examination of
      the available studies after HDMTX yielded more convincing alternative
      explanations for reduction in cure rate than over rescue. Little convincing
      evidence for the existence of over rescue after HDMTX was found. DISCUSSION: The
      rescue of high-dose MTX with an appropriate dose of folinic acid that can prevent
      toxicity, especially neurotoxicity, was not shown to reduce the therapeutic
      effect. No evidence was found that higher doses of folinic acid after high dose
      MTX reduces the therapeutic effect. CONSEQUENCES OF THE HYPOTHESIS: Acceptance of
      the hypothesis can prevent harm being caused (especially brain damage) by
      reversing the trend of dose reduction in FA rescue. The recognition that the use
      of higher folinic acid doses is safe, can prevent neurotoxicity, and does not
      reduce prognosis has important implications for the development of effective non
      toxic treatment protocols.

PMID- 24035690
TI  - Slow delivery of a nitrification inhibitor (dicyandiamide) to soil using a
      biodegradable hydrogel of chitosan.
AB  - Using chemical inhibitors to reduce soil nitrification decreases emissions of
      environmental damaging nitrate and nitrous oxide and improves nitrogen use
      efficiency in agricultural systems. The efficacy of nitrification inhibitors such
      as dicyandiamide (DCD) is limited in soil due to biodegradation. This study
      investigated if the persistence of DCD could be sustained in soil by slow release
      from a chitosan hydrogel. DCD was encapsulated in glyoxal-crosslinked chitosan
      beads where excess glyoxal was (i) partly removed (C beads) or (ii) allowed to
      dry (CG beads). The beads were tested in water and in soil. The beads contained
      two fractions of DCD: one which was quickly released in water, and one which was
      not. A large DCD fraction within C beads was readily available: 84% of total DCD
      bead content was released after 9h immersion in water, while between 74% and 98%
      was released after 7d in soil under low to high moisture conditions. A lower
      percentage of encapsulated DCD was readily released from CG beads: 19% after 9h
      in water, and 33% after 7d in soil under high rainfall conditions. Kinetic
      analysis indicated that the release in water occurred by quasi-Fickian diffusion.
      The results also suggest that DCD release was controlled by bead erosion and the
      leaching of glyoxal derivatives, predominantly a glyoxal-DCD adduct whose release
      was positively correlated with that of DCD (R(2)=0.99, p?0.0001). Therefore,
      novel chitosan/glyoxal composite beads show a promising slow-release potential in
      soil for agrochemicals like DCD. 

PMID- 24035691
TI  - Improvement of nutrient removal by optimizing the volume ratio of anoxic to
      aerobic zone in AAO-BAF system.
AB  - A two-sludge system, combining anaerobic/anoxic/aerobic process with biological
      aerated filter (AAO-BAF), is used to treat domestic wastewater with low COD/N
      ratio (around 3.6). The volume ratio of anoxic to aerobic zone (Vano/Vaer) of the
      AAO reactor gradually increased from 2:5 to 6:1, during which the nutrient
      removal was improved. However, phosphorous removal began to deteriorate
      noticeably while Vano/Vaer increased to 7:0. The favorable Vano/Vaer was between
      2.5:1 and 6:1. When Vano/Vaer was 6:1, the average removal efficiencies of COD,
      TN and PO4(3-) were 89+/-4%, 83+/-3% and 99+/-1%, respectively. This study
      suggested the AAO-BAF system could achieve efficient nitrogen and phosphorous
      removal with limited carbon source. 

PMID- 24035692
TI  - Proteomic analysis in Daphnia magna exposed to As(III), As(V) and Cd heavy metals
      and their binary mixtures for screening potential biomarkers.
AB  - In this study, the effects of three widespread heavy metals, As(III), As(V) and
      Cd, and their binary mixtures on the proteomic profile in D. magna were examined
      to screen novel protein biomarkers using the two-dimensional gel electrophoresis
      method (2DE). Ten 20d daphnia were exposed to the LC20 concentrations for each of
      a total of 8 treatments, including the control, As(III), As(V), Cd,
      [As(III)+As(V)], [As(III)+Cd], [As(V)+Cd], and [As(III), As(V), Cd], for 24h
      before protein isolation. Three replicates were performed for each treatment.
      These protein samples were employed for 2DE experiments with a pH gradient gel
      strip from pH 3 to pH 10. The protein spots were detected by a silver staining
      process and their intensities were analyzed by Progenesis software to discover
      the differentially expressed proteins (DEPs) in response to each heavy metal. A
      total of 117 differentially expressed proteins (DEPs) were found in daphnia
      responding to the 8 treatments and mapped onto a 2D proteome map, which provides
      some information of the molecular weight (MW) and pI value for each protein. All
      of these DEPs are considered as potential candidates for protein biomarkers in D.
      magna for detecting heavy metals in the aquatic ecosystem. Comparing the
      proteomic results among these treatments suggested that exposing D. magna to
      binary mixtures of heavy metals may result in some complex interactive molecular
      responses within them, rather than just the simple sum of the proteomic profiles
      of the individual chemicals, (As(III), As(V), and Cd). 

PMID- 24035693
TI  - Influence of the operation conditions on CO2 capture by CaO-derived sorbents
      prepared from synthetic CaCO3.
AB  - In this work, a statistical experimental design is performed in order to prepare
      CaCO3 materials for use as CaO-based CO2 sorbent precursors. The influence of
      different operational parameters such as synthesis temperature (ST), stirring
      rate (SR) and surfactant percent (SP) on CO2 capture is studied by applying
      Response Surface Methodology (RSM). The samples were characterized using
      different analytical techniques including X-ray diffraction, N2 adsorption
      isotherm analysis and Scanning Electron Microscopy-X-ray Energy Dispersive
      Spectroscopy (SEM-EDX). CO2 capture capacity was determined by means of a
      thermogravimetric analyzer which recorded the mass uptake of the samples when
      these were exposed to a gas stream containing diluted (15%) CO2. The statistical
      approach used in this work provides a rapid way of predicting and optimizing the
      main preparation variables of CaO-derived sorbents for CO2 sorption. The results
      obtained clearly indicate that four parameters statistically influence CO2
      uptake: SR, the square of SR, its interaction with SP and the square of SP. 

PMID- 24035695
TI  - [Prognosis of clinical patients according to length of stay in the intensive care
      unit].

PMID- 24035694
TI  - A journey toward Bioorthogonal Profiling of Protein Methylation inside living
      cells.
AB  - Human protein methyltransferases (PMTs) play essential roles through methylating
      histone and nonhistone targets. It is very challenging to profile global
      methylation (or methylome) in the context of relevant cellular settings. Unlike
      other posttranslational modifications such as lysine acetylation or
      Ser/Thr/Tyr/His phosphorylation, methylation of lysine or arginine does not
      significantly alter its physical properties (e.g. charge and size) and therefore
      may not be probed readily by conventional biological tools such antibodies. It is
      also not trivial to assign unambiguously dynamic methylation events to specific
      PMTs given their potential redundancy. This review focuses on the decade-long
      progress in developing complementary chemical tools to elucidate targets of
      designated PMTs. One of such efforts was to develop the Bioorthogonal Profiling
      of Protein Methylation (BPPM) technology in vitro and inside living cells. 

PMID- 24035696
TI  - [Role of plasma procalcitonin in the diagnosis of ventilator-associated
      pneumonia: systematic review and metaanalysis].
AB  - OBJECTIVE: To determine the role of plasma procalcitonin (PCT) levels in
      diagnosing ventilator-associated pneumonia. DESIGN: A systematic review of
      publications prospectively assessing the diagnostic role of PCT in ventilator
      associated pneumonia was carried out. The search was performed using Medline,
      Embase, the Cochrane Collaboration and MEDION, with reviewing of the references
      of retrieved articles. We extracted data that allowed the calculation of
      sensitivity, specificity, likelihood ratios and diagnostic odds ratio.
      Intervention Metaregression was performed to determine whether exposure to
      previous antibiotic treatment, the time to occurrence of ventilator-associated
      pneumonia and the type of patients had an impact upon the diagnostic performance
      of procalcitonin. RESULTS: Seven studies were considered (373 patients, 434
      episodes). We found no publication bias or threshold effect. High plasma PCT
      levels were associated to an increased risk of suffering ventilator-associated
      pneumonia (OR: 8.39; 95% CI: 5.4-12.6). The pooled data on sensitivity,
      specificity, positive and negative likelihood ratio, and diagnostic odds ratio
      found were 76% (69-82), 79% (74-84), 4.35 (2.48-7.62), 0.26 (0.15-0.46) and 17.9
      (10.1-31.7), respectively. Diagnostic yield was modified by prior exposure to
      antibiotics (rDOR 0.11, 0.02-0.069), but not by the type of critically ill
      patient or the time to occurrence of ventilator-associated pneumonia.
      CONCLUSIONS: Our results suggest that PCT provides additional information on the
      risk of VAP. Inclusion of PCT in diagnostic algorithms could improve their
      effectiveness.

PMID- 24035697
TI  - [Tissue oxygen saturation in the critically ill patient].
AB  - Hemodynamic resuscitation seeks to correct global macrocirculatory parameters of
      pressure and flow. However, current evidence has shown that despite the
      normalization of these global parameters, microcirculatory and regional perfusion
      alterations can persist, and these alterations have been independently associated
      with a poorer patient prognosis. This in turn has lead to growing interest in new
      technologies for exploring regional circulation and microcirculation. Near infra
      red spectroscopy allows us to monitor tissue oxygen saturation, and has been
      proposed as a noninvasive, continuous and easy-to-obtain measure of regional
      circulation. The present review aims to summarize the existing evidence on near
      infra-red spectroscopy and its potential clinical role in the resuscitation of
      critically ill patients in shock. 

PMID- 24035698
TI  - Clinical factors associated with success of proportional assist ventilation in
      the acute phase of critical illness: pilot study.
AB  - REASON: Proportional assist ventilation plus (PAV+) applies pressure depending on
      the patient's inspiratory effort, automatically adjusting flow and volume assist
      to changes in respiratory mechanics. We aimed to assess the clinical factors
      associated with the success of PAV+ as first-line support in the acute phase of
      critical illness. METHODS: A prospective cohort study was carried out.
      Mechanically ventilated patients>24h were switched from assist-control
      ventilation to PAV+ as soon as they regained spontaneous breathing activity. PAV+
      was set to deliver the highest assistance. We compared patients in whom PAV+
      succeeded versus those in whom it failed. RESULTS: PAV+ succeeded in 12 (63%)
      patients, but failed in 7 (37%) due to tachypnea (n=4), hypercapnia (n=2), and
      metabolic acidosis (n=1), but without statistical significance. Both groups had
      similar clinical parameters. On the day of inclusion, total work of breathing per
      breath was lower in the successful PAV+ group (WOBTOT: 0.95 [0.8-1.35] vs. 1.6
      [1.4-1.8] J/L; P<.007). The area under the ROC curve was 0.89 +/- 0.08 for
      WOBTOT. The best cut-off for predicting PAV+ success was WOBTOT<1.4 J/L
      (sensitivity: 1 [0.7-1], specificity: 0.6 [0.4-0.6], PPV: 0.7 [0.5-0.7], and NPV:
      1 [0.6-1]). CONCLUSION: PAV+ proved feasible as first-line ventilatory support in
      63% of the patients, mostly in individuals without extreme derangements in
      WOBTOT. Tachypnea and hypercapnia were the clinical factors associated with
      failure, though statistical significance was not reached.

PMID- 24035700
TI  - Noninvasive estimation of ventricular filling pressures in patients with single
      right ventricles.
AB  - BACKGROUND: Increased ventricular end-diastolic pressure (VEDP) is a known risk
      factor for morbidity and mortality in patients with single-ventricle physiology.
      Spectral Doppler tissue imaging (DTI) has been shown to modestly correlate with
      direct measurement of VEDP. Strain rate (SR) values, obtained via myocardial
      deformation, have not yet been compared with VEDP in this patient population. The
      goal of this study was to evaluate which of these imaging techniques correlates
      best with VEDP in patients with single-RV (RV) physiology. METHODS: Patients with
      single-RV physiology who underwent simultaneous echocardiography and
      catheterization were evaluated. Echocardiographic data included global
      longitudinal SR early diastolic wave (SRe) and SR late diastolic wave (SRa), DTI
      early diastolic wave (e') and DTI late diastolic wave (a') of the right
      ventricular free wall, and right atrioventricular valve inflow velocities (E and
      A waves). E/SRe and E/e' ratios were calculated. VEDP was obtained from the
      catheterization report. RESULTS: Twenty-seven studies were performed on patients
      with single-RV physiology. The median age at the time of catheterization was 11.4
      months (range, 0-132 months). The mean VEDP was 9.9 +/- 4.5 mm Hg. VEDP
      correlated significantly with E/SRe ratio (r = 0.88), global SRe (r = -0.52),
      SRe/SR late diastolic wave ratio (r = -0.42), and valve A velocity (r = 0.48).
      There were no significant correlations between VEDP and DTI measurements.
      Receiver operating characteristic curve analysis using an E/SRe cutoff of 150 cm
      showed 87.5% sensitivity and 78.9% specificity for predicting VEDP > 10 mm Hg.
      CONCLUSIONS: In patients with single-RV physiology, VEDP correlated strongly with
      SR but not with DTI measurements. SR measurements should be considered as a
      possible means to estimate VEDP in this complex patient population rather than
      DTI.

PMID- 24035699
TI  - Renal retention of lipid microbubbles: a potential mechanism for flank discomfort
      during ultrasound contrast administration.
AB  - BACKGROUND: The etiology of flank pain sometimes experienced during the
      administration of ultrasound contrast agents is unknown. The aim of this study
      was to investigate whether microbubble ultrasound contrast agents are retained
      within the renal microcirculation, which could lead to either flow disturbance or
      local release of vasoactive and pain mediators downstream from complement
      activation. METHODS: Retention of lipid-shelled microbubbles in the renal
      microcirculation of mice was assessed by confocal fluorescent microscopy and
      contrast-enhanced ultrasound imaging with dose-escalating intravenous injection.
      Studies were performed with size-segregated microbubbles to investigate physical
      entrapment, after glycocalyx degradation and in wild-type and C3-deficient mice
      to investigate complement-mediated retention. Urinary bradykinin was measured
      before and after microbubble administrations. Renal contrast-enhanced ultrasound
      in human subjects (n = 13) was performed 7 to 10 min after the completion of
      lipid microbubble administration. RESULTS: In both mice and humans, microbubble
      retention was detected in the renal cortex by persistent contrast-enhanced
      ultrasound signal enhancement. Microbubble retention in mice was linearly related
      to dose and occurred almost exclusively in cortical glomerular microvessels.
      Microbubble retention did not affect microsphere-derived renal blood flow.
      Microbubble retention was not influenced by glycocalyx degradation or by
      microbubble size, thereby excluding lodging, but was reduced by 90% (P < .01) in
      C3-deficient mice. Urinary bradykinin increased by 65% 5 min after microbubble
      injection. CONCLUSIONS: Lipid-shelled microbubbles are retained in the renal
      cortex because of complement-mediated interactions with glomerular microvascular
      endothelium. Microbubble retention does not adversely affect renal perfusion but
      does generate complement-related intermediates that are known to mediate
      nociception and could be responsible for flank pain.

PMID- 24035701
TI  - Genome-wide linkage scan of quantitative traits representing symptom dimensions
      in multiplex schizophrenia families.
AB  - Symptom dimensions of schizophrenia are likely to be the intermediate phenotypes
      under the control of disease-susceptibility genes, or separate traits related to
      disease-modifier genes. This study aimed to identify chromosomal loci linked to
      symptom dimensions of schizophrenia through genome-wide quantitative trait locus
      (QTL) linkage analysis. The study subjects consisted of 56 families with 183
      members including 123 affected individuals. Symptom evaluations were performed on
      lifetime basis. Through principal component factor analysis, eight quantitative
      phenotypes representing symptom dimensions were identified. Genotyping was done
      for 6008 SNP markers, and genome-wide QTL linkage analysis was performed. No
      symptom dimension showed a significant linkage attaining genome-wide empirical
      thresholds. We observed seven regions yielding linkage signals attaining genome
      wide empirical thresholds for suggestive linkage (NPL Z score = 2.78-3.49);
      chromosome 15q26.1 for 'non-paranoid delusion factor', 2p24.3 and 7q31.1 for
      'prodromal impairment factor', 1q32.1, 9p21.3, and 9q31.2 for 'negative symptom
      factor', and 10p13 for 'disorganization factor'. Among these loci, chromosome
      2p24.3 and 1q32.1 overlap with susceptibility loci of schizophrenia identified in
      our previous linkage studies. This study suggests the existence of genetic loci
      related to various clinical features of schizophrenia. Further genetic analyses
      for these dimensional phenotypes are warranted.

PMID- 24035702
TI  - Empathic competencies in violent offenders.
AB  - Violent offending has often been associated with a lack of empathy, but
      experimental investigations are rare. The present study aimed at clarifying
      whether violent offenders show a general empathy deficit or specific deficits
      regarding the separate subcomponents. To this end, we assessed three core
      components of empathy (emotion recognition, perspective taking, affective
      responsiveness) as well as skin conductance response (SCR) in a sample of 30 male
      violent offenders and 30 healthy male controls. Data analysis revealed reduced
      accuracy in violent offenders compared to healthy controls only in emotion
      recognition, and that a high number of violent assaults was associated with
      decreased accuracy in perspective taking for angry scenes. SCR data showed
      reduced physiological responses in the offender group specifically for fear and
      disgust stimuli during emotion recognition and perspective taking. In addition,
      higher psychopathy scores in the violent offender group were associated with
      reduced accuracy in affective responsiveness. This is the first study to show
      that mainly emotion recognition is deficient in violent offenders whereas the
      other components of empathy are rather unaffected. This divergent impact of
      violent offending on the subcomponents of empathy suggests that all three empathy
      components can be targeted by therapeutic interventions separately. 

PMID- 24035704
TI  - Hypomagnesemia and prehypertension in otherwise healthy individuals.
AB  - BACKGROUND: Given the potential implications in the policies focused on the
      prevention of hypertension, we evaluate the relationship between low serum
      magnesium levels and prehypertension in otherwise healthy subjects. METHODS: A
      cross-sectional study that enrolled 175 healthy men and non-pregnant women, 20 to
      65 years of age was carried out. Type 2 diabetes, impaired fasting glucose,
      hypertension, chronic diarrhea, cancer, impaired renal function, as well as the
      intake of magnesium supplements in the previous six months, were the exclusion
      criteria. Hypomagnesemia was defined by serum magnesium concentration of <0.7
      mmol/L and prehypertension by Systolic (S) and Diastolic (D) blood pressure (BP)
      of 120 to 139 and 80 to 89 mmHg. A multivariate logistic conditional forward
      analysis, adjusted by sex, age, alcohol consumption waist circumference, body
      mass index, fasting glucose and triglyceride levels was conducted to evaluate the
      association between hypomagnesemia and prehypertension. RESULTS: Prehypertension
      was identified in 68 (13.2%) subjects who were compared with 107 (20.8%) control
      individuals without prehypertension. Individuals with prehypertension showed
      lower magnesium (0.73+/-0.20 vs. 0.77+/-0.21, p<0.001) and higher triglyceride
      levels (2.8+/-3.5 vs. 1.8+/-1.2, p=0.04) as compared with non-prehypertensive
      individuals. There were no other significant differences between the groups. The
      adjusted multivariate logistic conditional forward analysis showed a significant
      association between hypomagnesemia and prehypertension (OR 1.98; 95% CI 1.11
      4.20, p=0.04). CONCLUSIONS: Our finding suggests that low serum magnesium levels
      could play an important role in the pathophysiology of prehypertension in
      otherwise healthy subjects.

PMID- 24035705
TI  - Long range epigenetic silencing is a trans-species mechanism that results in
      cancer specific deregulation by overriding the chromatin domains of normal cells.
AB  - DNA methylation and chromatin remodeling are frequently implicated in the
      silencing of genes involved in carcinogenesis. Long Range Epigenetic Silencing
      (LRES) is a mechanism of gene inactivation that affects multiple contiguous CpG
      islands and has been described in different human cancer types. However, it is
      unknown whether there is a coordinated regulation of the genes embedded in these
      regions in normal cells and in early stages of tumor progression. To better
      characterize the molecular events associated with the regulation and remodeling
      of these regions we analyzed two regions undergoing LRES in human colon cancer in
      the mouse model. We demonstrate that LRES also occurs in murine cancer in vivo
      and mimics the molecular features of the human phenomenon, namely, downregulation
      of gene expression, acquisition of inactive histone marks, and DNA
      hypermethylation of specific CpG islands. The genes embedded in these regions
      showed a dynamic and autonomous regulation during mouse intestinal cell
      differentiation, indicating that, in the framework considered here, the
      coordinated regulation in LRES is restricted to cancer. Unexpectedly, benign
      adenomas in Apc(Min/+) mice showed overexpression of most of the genes affected
      by LRES in cancer, which suggests that the repressive remodeling of the region is
      a late event. Chromatin immunoprecipitation analysis of the transcriptional
      insulator CTCF in mouse colon cancer cells revealed disrupted chromatin domain
      boundaries as compared with normal cells. Malignant regression of cancer cells by
      in vitro differentiation resulted in partial reversion of LRES and gain of CTCF
      binding. We conclude that genes in LRES regions are plastically regulated in cell
      differentiation and hyperproliferation, but are constrained to a coordinated
      repression by abolishing boundaries and the autonomous regulation of chromatin
      domains in cancer cells.

PMID- 24035706
TI  - Ageism perceived by the elderly in Taiwan following hip fracture.
AB  - This qualitative, longitudinal study explored the feelings about and responses to
      discrimination experiences related to perceived ageism of older persons following
      hip fracture. Five male and six female hip-fractured elderly patients were
      sampled from a medical center in northern Taiwan. Semi-structured questionnaires
      were used to explore participants' experiences of and responses to ageism-related
      experiences. Data were collected in face-to-face interviews during home visits at
      1, 3, 6, and 12 months after discharge from hospital, between June 2007 and
      December 2008. Textual data of participants' responses were analyzed by directed
      content analysis. All participants experienced ageism. In first 3 months after
      discharge, participants' main perceived ageism was positive because of their
      dependency and feeling overprotected by others. From 3 months to 1 year after
      discharge, other ageism experiences emerged: isolated because of physical
      restrictions and neglected. Furthermore, participants' responses were divided
      into two categories: disregard and tolerance of ageism, or becoming more
      independent because of ageism. The elderly participants considered that the
      influences of positive ageism in the early months after discharge reduced their
      autonomy and deprived them of power. This response to ageism was temporary; over
      time the participants tried to regain autonomy by overcoming their dependency and
      improving their physical functioning. 

PMID- 24035707
TI  - Appraisal of in vitro and in vivo antioxidant activity potential of cornelian
      cherry leaves.
AB  - The antioxidant activity of the 80% methanolic extract of Cornus mas L. leaves
      (CMM) was evaluated by various methods both in vitro and in vivo. In vitro
      screening tests indicated that CMM had high antioxidant activity in terms of free
      radical scavenging and metal reducing activity. In vivo antioxidant activity
      studies in normal healthy rats demonstrated that the total antioxidant capacity
      of liver homogenates were increased, although no changes were observed in the
      activities of antioxidant enzymes superoxide dismutase, catalase and glutathione
      peroxidase or in the level of lipid peroxidation. Studies on CCl4-treated rats
      also showed that CMM restored the activities of antioxidant enzymes, lowered the
      level of lipid peroxidation and elevated the total antioxidant capacities of both
      the total blood and liver homogenates of the animals. Further activity-guided
      fractionation studies led to the isolation of gallic acid, a well-known
      antioxidant, as one of the active components. 

PMID- 24035708
TI  - A multiplexed assay to detect antimicrobial peptides in biological fluids and
      cell secretions.
AB  - Mucosal tissues represent the front line in defense against potential pathogens,
      and one means by which mucosa provide protection is via the secretion of
      antimicrobials which can interfere with potential pathogens as well as recruit
      and modify the responses of immune cells. Here we describe adaptation of ELISA
      assays to microsphere format, facilitating simultaneous quantification of
      antimicrobial peptides including elafin, MIP3alpha, HBD2, HBD3, SLPI, RANTES,
      SDF1, lactoferrin, LL-37, and HNP1-3. The multiplexed assay exhibits excellent
      reproducibility, shows linearity over a two order of magnitude concentration
      range for most analytes, is compatible with biological fluids such as
      cervicovaginal lavage fluid, and presents significant cost and sample savings
      relative to traditional ELISA assays. 

PMID- 24035709
TI  - Structure of the fibrillin-1 N-terminal domains suggests that heparan sulfate
      regulates the early stages of microfibril assembly.
AB  - The human extracellular matrix glycoprotein fibrillin-1 is the primary component
      of the 10- to 12-nm-diameter microfibrils, which perform key structural and
      regulatory roles in connective tissues. Relatively little is known about the
      molecular mechanisms of fibrillin assembly into microfibrils. Studies using
      recombinant fibrillin fragments indicate that an interaction between the N- and C
      terminal regions drives head-to-tail assembly. Here, we present the structure of
      a fibrillin N-terminal fragment comprising the fibrillin unique N-terminal (FUN)
      and the first three epidermal growth factor (EGF)-like domains (FUN-EGF3). Two
      rod-like domain pairs are separated by a short, flexible linker between the EGF1
      and EGF2 domains. We also show that the binding site for the C-terminal region
      spans multiple domains and overlaps with a heparin interaction site. These data
      suggest that heparan sulfate may sequester fibrillin at the cell surface via FUN
      EGF3 prior to aggregation of the C terminus, thereby regulating microfibril
      assembly.

PMID- 24035703
TI  - Joint use of cardio-embolic and bleeding risk scores in elderly patients with
      atrial fibrillation.
AB  - BACKGROUND: Scores for cardio-embolic and bleeding risk in patients with atrial
      fibrillation are described in the literature. However, it is not clear how they
      co-classify elderly patients with multimorbidity, nor whether and how they affect
      the physician's decision on thromboprophylaxis. METHODS: Four scores for cardio
      embolic and bleeding risks were retrospectively calculated for >= 65 year old
      patients with atrial fibrillation enrolled in the REPOSI registry. The co
      classification of patients according to risk categories based on different score
      combinations was described and the relationship between risk categories tested.
      The association between the antithrombotic therapy received and the scores was
      investigated by logistic regressions and CART analyses. RESULTS: At admission,
      among 543 patients the median scores (range) were: CHADS2 2 (0-6), CHA2DS2-VASc 4
      (1-9), HEMORR2HAGES 3 (0-7), HAS-BLED 2 (1-6). Most of the patients were at high
      cardio-embolic/high-intermediate bleeding risk (70.5% combining CHADS2 and
      HEMORR2HAGES, 98.3% combining CHA2DS2-VASc and HAS-BLED). 50-60% of patients were
      classified in a cardio-embolic risk category higher than the bleeding risk
      category. In univariate and multivariable analyses, a higher bleeding score was
      negatively associated with warfarin prescription, and positively associated with
      aspirin prescription. The cardio-embolic scores were associated with the
      therapeutic choice only after adjusting for bleeding score or age. CONCLUSION:
      REPOSI patients represented a population at high cardio-embolic and bleeding
      risks, but most of them were classified by the scores as having a higher cardio
      embolic than bleeding risk. Yet, prescription and type of antithrombotic therapy
      appeared to be primarily dictated by the bleeding risk.

PMID- 24035710
TI  - Conformational transition of membrane-associated terminally acylated HIV-1 Nef.
AB  - Many proteins are posttranslationally modified by acylation targeting them to
      lipid membranes. While methods such as X-ray crystallography and nuclear magnetic
      resonance are available to determine the structure of folded proteins in
      solution, the precise position of folded domains relative to a membrane remains
      largely unknown. We used neutron and X-ray reflection methods to measure the
      displacement of the core domain of HIV Nef from lipid membranes upon insertion of
      the N-terminal myristate group. Nef is one of several HIV-1 accessory proteins
      and an essential factor in AIDS progression. Upon insertion of the myristate and
      residues from the N-terminal arm, Nef transitions from a closed-to-open
      conformation that positions the core domain 70 A from the lipid headgroups. This
      work rules out previous speculation that the Nef core remains closely associated
      with the membrane to optimize interactions with the cytoplasmic domain of MHC-1.

PMID- 24035711
TI  - High-resolution comparative modeling with RosettaCM.
AB  - We describe an improved method for comparative modeling, RosettaCM, which
      optimizes a physically realistic all-atom energy function over the conformational
      space defined by homologous structures. Given a set of sequence alignments,
      RosettaCM assembles topologies by recombining aligned segments in Cartesian space
      and building unaligned regions de novo in torsion space. The junctions between
      segments are regularized using a loop closure method combining fragment
      superposition with gradient-based minimization. The energies of the resulting
      models are optimized by all-atom refinement, and the most representative low
      energy model is selected. The CASP10 experiment suggests that RosettaCM yields
      models with more accurate side-chain and backbone conformations than other
      methods when the sequence identity to the templates is greater than ~15%.

PMID- 24035712
TI  - A retrospective analysis of peripheral T-cell lymphoma treated with the intention
      to transplant in the first remission.
AB  - BACKGROUND: Peripheral T-cell lymphomas are aggressive lymphomas that have no
      standard treatment. Studies suggest that HD-ASCT in the first CR improves
      outcome. Few data exist regarding allo-HSCT in the first CR. PATIENTS AND
      METHODS: We retrospectively identified patients (2001-2011) with PTCL-not
      otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic lymphoma
      kinase-negative anaplastic large cell lymphoma, initially treated with CHOP, CHOP
      ICE (ifosfamide, carboplatin, etoposide), or other therapy with the intention to
      transplant in the first CR. Disease characteristics, therapy, progression-free
      survival (PFS), and OS were evaluated. RESULTS: Sixty-five patients were
      identified. PFS and OS were 38% and 52%, respectively, at 4 years. CHOP and CHOP
      ICE regimens had similar outcomes. Treatment with allo-HSCT and HD-ASCT had OS at
      4 years of 66% and 67%, respectively. Patients who did not proceed to transplant
      had OS of 27%. IPI score <= 2 and Prognostic Index for T-cell Lymphomas scores <=
      1 predicted improved outcome. Combined analysis of interim response to CHOP and
      IPI score also predicted PFS and OS. CONCLUSION: Our results support
      consolidation of first CR with transplantation. The addition of etoposide did not
      improve outcomes. Baseline IPI and interim response to CHOP can predict outcomes
      and guide decisions about transplantation in first CR in PTCL. Randomized trials
      are necessary to confirm the efficacy of this approach.

PMID- 24035713
TI  - Primary cutaneous gamma-delta T-cell lymphoma with marked pagetoid
      epidermotropism shortly after allogeneic stem cell transplantation.

PMID- 24035714
TI  - Multiple myeloma international staging system: "staging" or simply "aging"
      system?
AB  - Because of the wide variation in multiple myeloma (MM) survival, numerous studies
      have focused over the past 40 years on the biological and cytogenetic prognostic
      values in MM patients. Since 2005, the MM International Staging System (ISS) has
      recognized the combination of beta-2 microglobulin (beta2M) with serum albumin
      (SA) concentrations as the most simple and potent combination to determine the
      prognosis in MM patients. Curiously, the reasons for the efficiency of the
      combination of beta2M with SA remain not clear-cut. In 2007, Fonseca and San
      Miguel (Prognostic factors and staging in multiple myeloma. Hematol Oncol Clin
      North Am 2007; 21:1115-40) underlined that cytogenetic assessment might also be
      useful for evaluating MM prognosis. Furthermore, new perspectives recently
      appeared with the genomic approach. Here, we (1) question the specific rationale
      for beta2M and SA as prognostic markers in MM, (2) emphasize the well-documented
      prognostic implications of beta2M and SA as potent biomarkers of comorbidity in
      older adults, and (3) conclude that the current MM-ISS is rather a staging system
      for age-related comorbidity burden (ie, aging system) than a specific MM staging
      system, and should not be used alone. Thus, we suggest that: (1) cytogenetics
      with the superscript MM-ISS could be the standard method; (2) some factors
      discovered using genomics could reflect the comorbidity burden and the intrinsic
      malignancy of MM clone, and thus needs more investigation; and (3) while waiting
      for standard genomic classification. 

PMID- 24035715
TI  - Chemoimmunotherapy and withdrawal of immunosuppression for monomorphic
      posttransplant lymphoproliferative disorders.
AB  - BACKGROUND: Monomorphic PTLDs are the most aggressive type of PTLD occurring
      after SOT. Current guidelines for treatment suggest a stepwise approach that
      includes a reduction of immunosuppression (RIS) with or without rituximab,
      followed by chemotherapy if there is no response. Nevertheless, recommendations
      regarding the extent and duration of RIS are nonstandardized and RIS as an
      initial strategy might be associated with an unacceptably high frequency of graft
      loss and disease progression. PATIENTS AND METHODS: We reviewed the outcome of a
      combination program of aggressive chemoimmunotherapy and complete withdrawal of
      immunosuppression in treating 22 patients with monomorphic PTLD between January
      1995 and August 2012. RESULTS: Twelve of 22 patients (55%) received CHOP-R
      (cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab) every 2
      weeks (dose-dense CHOP-R) and 10 patients received other doxorubicin-based
      regimens. There was no treatment-related mortality. Complete response was seen in
      91% of patients. Median OS was 9.61 years (95% confidence interval (CI), 5.21
      10.74). Median progression-free survival was 5.39 years (95% CI, 2.10-10.74). The
      graft rejection rate was 18% (95% CI, 0.03-0.34). CONCLUSION: The use of
      aggressive chemoimmunotherapy in combination with the withdrawal of
      immunosuppression approach yields excellent results and should be prospectively
      studied in a multi-institutional setting.

PMID- 24035717
TI  - Morphologically controlled preparation of CuO nanostructures under ultrasound
      irradiation and their evaluation as pseudocapacitor materials.
AB  - Various morphologies of copper oxide (CuO) nanostructures have been synthesized
      by controlling the reaction parameters in a sonochemical assisted method without
      using any templates or surfactants. The effect of reaction parameters including
      molar ratio of the reactants, reaction temperature, ultrasound exposure time, and
      annealing temperature on the composition and morphology of the product(s) has
      been investigated. The prepared samples have been characterized by X-ray
      diffraction (XRD), field emission scanning electron microscopy (FESEM), energy
      dispersive X-ray (EDAX), and thermogravimetric analysis (TGA). It has been found
      that Cu2(OH)3NO3 nanoplatelets are achieved in mild conditions which can be then
      converted to various morphologies of CuO nanostructures by either using high
      concentrations of OH(-) (formation of nanorods), prolonging sonication
      irradiation (nanoparticles), or thermal treatment (nanospheres). Application of
      the prepared CuO nanostructures was evaluated as supercapacitive material in 1 M
      Na2SO4 solution using cyclic voltammetry (CV) in different potential scan rates
      ranging from 5 to 100 mV s(-1). The specific capacitance has been calculated
      using CV curves. It has been found that the pseudocapacitor performance of CuO
      can be tuned via employing morphologically controlled samples. Accordingly, the
      prolonged sonicated sample (nanoparticles) showed the high specific capacitance
      of 158 F.g(-1).

PMID- 24035718
TI  - Studies on growth morphology, UV absorbance and luminescence properties of
      sulphur doped ZnO nanopowders synthesized by the application of ultrasound with
      varying input power.
AB  - Sulphur doped ZnO nanopowders have been prepared by sonochemical method in
      continuous (CS) and pulsed (PS) modes. Precipitation time was found to vary with
      input power of applied ultrasound. X-ray diffraction studies show the formation
      hexagonal wurtzite phase of nano ZnO but variation in size, strain and lattice
      parameters was observed in the samples synthesized through CS and PS modes with
      different input power. Surface morphology of the samples changed significantly
      with input power of the pulse as observed from scanning electron microscopic
      results. Well defined and c-axis oriented nanorods and multipodes were observed
      with power setting of 187.5 W whereas in all other cases no definite morphology
      was observed. UV absorption studies show higher value of absorbance for ZnO:S.
      Further, the absorption band becomes sharp for the samples prepared with power
      setting of 225 W. PL spectra show several bands due to different transitions in
      the region of 400-780 nm which have been explained in the light of excitonic and
      defect induced transitions in ZnO.

PMID- 24035719
TI  - Sonochemical and hydrodynamic cavitation reactors for laccase/hydrogen peroxide
      cotton bleaching.
AB  - The main goal of this work is to develop a novel and environmental-friendly
      technology for cotton bleaching with reduced processing costs. This work exploits
      a combined laccase-hydrogen peroxide process assisted by ultrasound. For this
      purpose, specific reactors were studied, namely ultrasonic power generator type
      K8 (850 kHz) and ultrasonic bath equipment Ultrasonic cleaner USC600TH (45 kHz).
      The optimal operating conditions for bleaching were chosen considering the
      highest levels of hydroxyl radical production and the lowest energy input. The
      capacity to produce hydroxyl radicals by hydrodynamic cavitation was also
      assessed in two homogenizers, EmulsiFlex(r)-C3 and APV-2000. Laccase
      nanoemulsions were produced by high pressure homogenization using BSA (bovine
      serum albumin) as emulsifier. The bleaching efficiency of these formulations was
      tested and the results showed higher whiteness values when compared to free
      laccase. The combination of laccase-hydrogen peroxide process with ultrasound
      energy produced higher whiteness levels than those obtained by conventional
      methods. The amount of hydrogen peroxide was reduced 50% as well as the energy
      consumption in terms of temperature (reduction of 40  degrees C) and operating
      time (reduction of 90 min).

PMID- 24035720
TI  - Phase transitions of perfluorocarbon nanoemulsion induced with ultrasound: a
      mathematical model.
AB  - While ultrasound has been used in many medical and industrial applications, only
      recently has research been done on phase transformations induced by ultrasound.
      This paper presents a numerical model and the predicted results of the phase
      transformation of a spherical nanosized droplet of perfluorocarbon in water. Such
      a model has applications in acoustic droplet vaporization, the generation of gas
      bubbles for medical imaging, therapeutic delivery and other biomedical
      applications. The formation of a gas phase and the subsequent bubble dynamics
      were studied as a function of acoustic parameters, such as frequency and
      amplitude, and of the physical aspects of the perfluorocarbon nanodroplets, such
      as chemical species, temperature, droplet size and interfacial energy. The model
      involves simultaneous applications of mass, energy and momentum balances to
      describe bubble formation and collapse, and was developed and solved numerically.
      It was found that, all other parameters being constant, the maximum bubble size
      and collapse velocity increases with increasing ultrasound amplitude, droplet
      size, vapor pressure and temperature. The bubble size and collapse velocity
      decreased with increasing surface tension and frequency. These results correlate
      with experimental observations of acoustic droplet vaporization. 

PMID- 24035716
TI  - CXC chemokine receptor 4 expression, CXC chemokine receptor 4 activation, and
      wild-type nucleophosmin are independently associated with unfavorable prognosis
      in patients with acute myeloid leukemia.
AB  - BACKGROUND: CXC chemokine receptor 4 (CXCR4) is activated by phosphorylation and
      essential for migration of hematopoietic precursors to bone marrow. CXCR4
      overexpression predicts unfavorable prognosis in patients with acute myeloid
      leukemia (AML). Nucleophosmin (NPM1) mutation is the most frequent genetic
      abnormality in patients with AML and predicts a favorable prognosis. In vitro
      studies have suggested that mutant nucleophosmin (NPM) decreases CXCR4-mediated
      chemotaxis by downregulating CXCR4, thereby linking the NPM and CXCR4 pathways.
      PATIENTS AND METHODS: In a group of 117 untreated adults with AML, we used
      immunohistochemistry to assess bone marrow specimens for CXCR4 and phosphorylated
      CXCR4 (pCXCR4) expression. All cases also were analyzed for NPM1 mutations using
      polymerase chain reaction-based methods. RESULTS: CXCR4 expression was detected
      in 75 patients (64%), and pCXCR4 expression was detected in 31 patients (26%).
      NPM1 mutations were detected in 63 patients (54%). NPM1 mutations did not
      correlate with CXCR4 (P = .212) or pCXCR4 (P = .355) expression. The median 5
      year overall survival was 27% (95% confidence interval, 19-36), with a median
      follow-up of 8 months (95% confidence interval, 6-15). In a multivariate Cox
      proportional hazards model, reduced overall and progression-free survival rates
      were associated with a history of antecedent hematologic disorder, failure to
      achieve complete remission, thrombocytopenia, unfavorable cytogenetics, CXCR4
      expression, and wild-type NPM1. pCXCR4 expression was independently associated
      with shorter progression-free survival. CONCLUSIONS: There is no correlation
      between NPM1 mutations and CXCR4 or pCXCR4 expression, suggesting that the CXCR4
      and NPM pathways act independently in adult AML.

PMID- 24035721
TI  - Slug is a key mediator of hypoxia induced cadherin switch in HNSCC: correlations
      with poor prognosis.
AB  - OBJECTIVES: According to recent studies, the function of Slug in hypoxia induced
      cadherin switch differs from cancer to cancer. Whether Slug is an essential
      mediator of the tumor hypoxia induced cadherin switch in head and neck squamous
      cell carcinoma (HNSCC) and the prognostic role of Slug in HNSCC patients are not
      elucidated. The aim of this study is to investigate the role of the Slug in
      cadherin switch induced by hypoxia in HNSCC. MATERIALS AND METHODS: Two HNSCC
      cell lines and 119 HNSCC specimens were selected for the present experiments. E/N
      cadherins expression and tumor cell invasion responding to hypoxia/HIF-1alpha
      overexpression and the silence of Slug/SnaI2 gene were detected in vitro. HNSCC
      specimens were analyzed by immunohistochemistry staining to correlate the
      expressions of Slug, HIF-1alpha and E/N-cadherins with clinical outcomes. RESULTS
      AND CONCLUSION: Our research evidenced that Slug was extremely elevated in the
      HNSCC cells in response to hypoxia/HIF-1alpha overexpression. Suppressing Slug
      expression impaired HIF-1alpha induced cadherin switch and tumor invasion. In
      HNSCC tissues, relatively high expression of Slug was detected to be associated
      with endogenous HIF-1alpha overexpression, cadherin switch, the risk of lymph
      node metastasis, and a more advanced TNM stage. Additionally, aberrant Slug
      expression combined with HIF-1alpha overexpression and cadherin switch was
      significantly correlated with shorter HNSCC patient survival. In conclusion, Slug
      is necessary for hypoxia-induced cadherin switch in HNSCC and may be used as a
      potential risk marker in predicting HNSCC clinical outcomes.

PMID- 24035722
TI  - Global analysis of DNA methylation changes during progression of oral cancer.
AB  - OBJECTIVES: Earlier studies involving a priori gene selection have identified
      promoter regions deregulated by DNA methylation changes in oral squamous cell
      cancers (OSCCs) and precancers. Interrogation of global DNA methylation patterns
      for such specimens has not been reported, though such analyses are needed to
      uncover novel molecular factors driving disease. MATERIALS AND METHODS: We
      evaluated global DNA methylation patterns for 30 biopsies obtained from 10
      patients undergoing surgical removal of an OSCC or carcinoma in situ (CIS). From
      a disease field in each patient, we collected (i) dysplastic, (ii) CIS or OSCC,
      and (iii) adjacent normal biopsies. DNA isolated from each biopsy was profiled
      for methylation status using the Illumina HumanMethylation27K platform. RESULTS:
      Our data demonstrate that aberrant methylation of promoter CpG islands exists
      across oral precancer and OSCC genomes. Non-hierarchical clustering of all
      methylation data revealed distinct methylation patterns between the normal and
      the CIS/OSCC tissues (with results for dysplastic biopsies split between groups).
      Multiple genes exhibiting recurrent aberrant DNA methylation were found for both
      dysplastic and CIS/OSCC groups, and included enrichment for genes found in the
      WNT and MAPK signaling pathways. CONCLUSION: In identifying aberrant DNA
      methylation at the earliest stages of oral precancer and finding recurring
      epigenetic disruption of specific genes/pathways across our analyzed cohort, we
      see evidence that CpG methylation changes may play a role in oral cancer
      progression and that global DNA methylation analyses may have significant utility
      in wider studies that seek to derive biomarkers or potentially druggable targets
      to improve oral cancer outcomes.

PMID- 24035724
TI  - A 3-D geometric morphometric study of intraspecific variation in the ontogeny of
      the temporal bone in modern Homo sapiens.
AB  - This study addresses how the human temporal bone develops the population-specific
      pattern of morphology observed among adults and at what point in ontogeny those
      patterns arise. Three-dimensional temporal bone shape was captured using 15
      landmarks on ontogenetic series of specimens from seven modern human populations.
      Discriminant function analysis revealed that population-specific temporal bone
      morphology is evident early in ontogeny, with significant shape differences among
      many human populations apparent prior to the eruption of the first molar. As
      early as five years of age, temporal bone shape reflects population history and
      can be used to reliably sort populations, although those in closer geographic
      proximity and molecular affinity are more likely to be misclassified. The
      deviation of cold-adapted populations from this general pattern of congruence
      between temporal bone morphology and genetic distances, identified in previous
      work, was confirmed here in adult and subadult specimens, and was revealed to
      occur earlier in ontogeny than previously recognized. Significant differences
      exist between the ontogenetic trajectories of some pairs of populations, but not
      among others, and the angles of these trajectories do not reflect genetic
      relationships or final adult temporal bone size. Significant intrapopulation
      differences are evident early in ontogeny, with differences becoming amplified by
      divergent trajectories in some groups. These findings elucidate how the
      congruence between adult human temporal bone morphology and population history
      develops, and reveal that this pattern corresponds closely to that described
      previously for facial ontogeny. 

PMID- 24035723
TI  - Characterization of tumorigenic cell lines from the recurrence and lymph node
      metastasis of a human salivary mucoepidermoid carcinoma.
AB  - The long-term outcome of patients with mucoepidermoid carcinoma is poor. Limited
      availability of cell lines and lack of xenograft models is considered a major
      barrier to improved mechanistic understanding of this disease and development of
      effective therapies. OBJECTIVE: To generate and characterize human mucoepidermoid
      carcinoma cell lines and xenograft models suitable for mechanistic and
      translational studies. METHODS: Five human mucoepidermoid carcinoma specimens
      were available for generation of cell lines. Cell line tumorigenic potential was
      assessed by transplantation and serial in vivo passaging in immunodeficient mice,
      and cell line authenticity verified by short tandem repeat (STR) profiling.
      RESULTS: A unique pair of mucoepidermoid carcinoma cell lines was established
      from a local recurrence (UM-HMC-3A) and from the metastatic lymph node (UM-HMC
      3B) of the same patient, 4 years after surgical removal of the primary tumor.
      These cell lines retained epithelial-like morphology through 100 passages in
      vitro, contain the Crtc1-Maml2 fusion oncogene (characteristic of mucoepidermoid
      carcinomas), and express the prototypic target of this fusion (NR4A2). Both cell
      lines generated xenograft tumors when transplanted into immunodeficient mice.
      Notably, the xenografts exhibited histological features and Periodic Acid Schiff
      (PAS) staining patterns that closely resembled those found in human tumors. STR
      profiling confirmed the origin and authenticity of these cell lines. CONCLUSION:
      These data demonstrate the generation and characterization of a pair of
      tumorigenic salivary mucoepidermoid carcinoma cell lines representative of
      recurrence and lymph node metastasis. Such models are useful for mechanistic and
      translational studies that might contribute to the discovery of new therapies for
      mucoepidermoid carcinoma.

PMID- 24035725
TI  - Current and future biologic markers for disease progression and relapse in
      testicular germ cell tumors: a review.
AB  - Testicular germ cell tumors represent a biologically unique disease process.
      These tumors are exquisitely sensitive to platinum-based chemotherapy, can be
      cured with surgical metastasectomy, and are known for the integration of biologic
      markers to stage and assign risk. Exploring further biologic markers that offer
      insight into the molecular mechanisms that contribute to disease biology is
      important. In this review, we attempt to summarize the utility of the current and
      some future biologic markers for disease monitoring and relapse. 

PMID- 24035726
TI  - Removal of H2S using molten carbonate at high temperature.
AB  - Gasification is considered to be an effective process for energy conversion from
      various sources such as coal, biomass, and waste. Cleanup of the hot syngas
      produced by such a process may improve the thermal efficiency of the overall
      gasification system. Therefore, the cleanup of hot syngas from biomass
      gasification using molten carbonate is investigated in bench-scale tests. Molten
      carbonate acts as an absorbent during desulfurization and dechlorination and as a
      thermal catalyst for tar cracking. In this study, the performance of molten
      carbonate for removing H2S was evaluated. The temperature of the molten carbonate
      was set within the range from 800 to 1000  degrees C. It is found that the
      removal of H2S is significantly affected by the concentration of CO2 in the
      syngas. When only a small percentage of CO2 is present, desulfurization using
      molten carbonate is inadequate. However, when carbon elements, such as char and
      tar, are continuously supplied, H2S removal can be maintained at a high level. To
      confirm the performance of the molten carbonate gas-cleaning system, purified
      biogas was used as a fuel in power generation tests with a molten carbonate fuel
      cell (MCFC). The fuel cell is a high-performance sensor for detecting gaseous
      impurities. When purified gas from a gas-cleaning reactor was continuously
      supplied to the fuel cell, the cell voltage remained stable. Thus, the molten
      carbonate gas-cleaning reactor was found to afford good gas-cleaning performance.

PMID- 24035727
TI  - Depollution benchmarks for capacitors, batteries and printed wiring boards from
      waste electrical and electronic equipment (WEEE).
AB  - The article compiles and analyses sample data for toxic components removed from
      waste electronic and electrical equipment (WEEE) from more than 30 recycling
      companies in Switzerland over the past ten years. According to European and Swiss
      legislation, toxic components like batteries, capacitors and printed wiring
      boards have to be removed from WEEE. The control bodies of the Swiss take back
      schemes have been monitoring the activities of WEEE recyclers in Switzerland for
      about 15 years. All recyclers have to provide annual mass balance data for every
      year of operation. From this data, percentage shares of removed batteries and
      capacitors are calculated in relation to the amount of each respective WEEE
      category treated. A rationale is developed, why such an indicator should not be
      calculated for printed wiring boards. The distributions of these de-pollution
      indicators are analysed and their suitability for defining lower threshold values
      and benchmarks for the depollution of WEEE is discussed. Recommendations for
      benchmarks and threshold values for the removal of capacitors and batteries are
      given.

PMID- 24035728
TI  - Does methotrexate administration for ectopic pregnancy after in vitro
      fertilization impact ovarian reserve or ovarian responsiveness?
AB  - OBJECTIVE: To evaluate the effects of methotrexate (MTX) on the future fertility
      of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness
      in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX.
      DESIGN: Retrospective cohort study. SETTING: Private reproductive endocrinology
      and infertility practice. PATIENT(S): Sixty-six women undergoing IVF before and
      after receiving MTX for an EP. INTERVENTION(S): Methotrexate administration and
      ovarian stimulation. MAIN OUTCOME MEASURE(S): Markers of ovarian reserve (day 3
      FSH, antral follicle count), measures of ovarian responsiveness (duration of
      stimulation, peak E2 level, total dose of gonadotropins, number of oocytes
      retrieved, fertilization rate), and time from MTX administration to subsequent
      IVF cycle. RESULT(S): There were no differences after MTX administration in body
      mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins
      was used in the cycle after MTX, but there were no differences in numbers of
      oocytes retrieved or high quality embryos transferred. As expected, there was a
      slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were
      comparable to the average PRs within the practice when combining all age groups.
      CONCLUSION(S): Methotrexate remains the first line of therapy for medical
      management of asymptomatic EP and does not compromise ovarian reserve, ovarian
      responsiveness, or IVF success in subsequent cycles.

PMID- 24035729
TI  - Spinal surgery in a patient with essential thrombocythemia resulting in leg
      paraplegia: a case report.
AB  - BACKGROUND CONTEXT: Essential thrombocythemia (ET) is a chronic
      myeloproliferative disorder characterized by a relatively benign clinical course
      that may be complicated by conflicting thrombosis and bleeding. Postoperative
      spinal epidural hematoma is an uncommon, but well-known, complication after
      spinal surgery. PURPOSE: To describe a patient with ET who underwent surgery for
      lumbar spinal canal stenosis resulting in leg paraplegia and discuss the
      perioperative management for ET. STUDY DESIGN: Case report. RESULTS: The patient
      with ET underwent laminoplasty and posterolateral fusion for degenerative
      spondylolisthesis and spinal stenosis at L4-L5. A hematoma was observed in the
      epidural cavity after surgery, and emergency surgical evacuation was performed.
      After revision surgery, bleeding from the wound continued for 2 months, despite
      transfusions of platelets and coagulation factors, and right unilateral leg
      paralysis developed. CONCLUSIONS: This case presentation increases the awareness
      of this disorder to the spinal community and the need to establish guidelines for
      the perioperative management of patients who require surgery in similar settings.

PMID- 24035730
TI  - The biomechanical influence of the facet joint orientation and the facet tropism
      in the lumbar spine.
AB  - BACKGROUND CONTEXT: Facet joint orientation and facet tropism (FT) are presented
      as the potential anatomical predisposing factors for lumbar degenerative changes
      that may lead in turn to early degeneration and herniation of the corresponding
      disc or degenerative spondylolisthesis. However, no biomechanical study of this
      concept has been reported. PURPOSE: To investigate the biomechanical influence of
      the facet orientation and FT on stress on the corresponding segment. STUDY
      DESIGN: Finite element analysis. METHODS: Three models, F50, F55, and F60 were
      simulated with different facet joint orientations (50 degrees , 55 degrees , and
      60 degrees  relative to coronal plane) at both L2-L3 facet joints. A FT model was
      also simulated to represent a 50 degrees  facet joint angle at the right side and
      a 60 degrees  facet joint angle at the left side in the L2-L3 segment. In each
      model, the intradiscal pressures were investigated under four pure moments and
      anterior shear force. Facet contact forces at the L2-L3 segment were also
      analyzed under extension and torsion moments and anterior shear force. This study
      was supported by 5000 CHF grant of 2011 AO Spine Research Korea fund. The authors
      of this study have no topic-specific potential conflicts of interest related to
      this study. RESULTS: The F50, F55, and F60 models did not differ in the
      intradiscal pressures generated under four pure moments: but under anterior shear
      force, the F60 and FT models showed increases of intradiscal pressure. The F50
      model under extension and the F60 model under torsion each generated an increase
      in facet contact force. In all conditions tested, the FT model yielded the
      greatest increase of intradiscal pressure and facet contact force of all the
      models. CONCLUSIONS: The facet orientation per se did not increase disc stress or
      facet joint stress prominently at the corresponding level under four pure
      moments, but FT could make the corresponding segment more vulnerable to external
      moments or anterior shear force.

PMID- 24035731
TI  - Surgical treatment based on pedicle screw instrumentation for thoracic or lumbar
      spinal Langerhans cell histiocytosis complicated with neurologic deficit in
      children.
AB  - BACKGROUND CONTEXT: Surgical indications and procedures for spinal Langerhans
      cell histiocytosis (LCH) in children are still controversial. Reports containing
      large samples of surgically treated patients are few in the currently available
      literature, and the reported operative procedures were also somewhat obsolete.
      So, further investigation based on large-sample cases and using improved surgical
      techniques is beneficial and helpful to refine the treatment strategy. PURPOSE:
      To recommend a reasonable treatment strategy for thoracic or lumbar spine LCH in
      children complicated with neurologic deficit. STUDY DESIGN/SETTING:
      Retrospective/academic medical center. PATIENT SAMPLE: Twelve children aged from
      2 to 16 years old with the diagnosis of thoracic or lumbar spinal LCH accompanied
      by neurologic deficit received surgical treatment from January 2005 to January
      2010. OUTCOME MEASURES: Frankel scale for neurologic function, fusion of the
      mass, and recurrence of the lesion. METHODS: All 12 patients presented initially
      with local pain and progressive neurologic detriment. Neurologic evaluation
      revealed two patients with Frankel Grade B, eight with Grade C, and two with
      Grade D. Radiographic features were positive for typical vertebra plana, a space
      occupying mass in the spinal canal compressing neural elements, and a spinal
      canal encroachment rate more than 50%. Posterior instrumentation with pedicle
      screw combined with anterior corpectomy, decompression, and support bone graft
      was performed in the first seven patients as a one-stage procedure. In the
      remaining five patients, posterior pedicle screw fixation, laminectomy for
      decompression (via excision of the tumor-like mass), and repair of laminae with
      allograft bone block were performed. The collapsed vertebral body was left
      untouched. No chemotherapy or radiotherapy was administrated postoperatively in
      any of the cases. RESULTS: The mean follow-up duration was 43.3 months. The mean
      operation time was 330 minutes with combined procedure and 142 minutes with
      single posterior approach (p=.000). The average blood loss was 933 mL with
      combined procedure and 497 mL with single posterior approach (p=.039). Three of
      seven patients who received combined surgery encountered approach-related
      complications, that is, one with intercostal neuralgia and two with pleural
      effusion. No severe neurologic deteriorate, instrumentation failure, or disease
      recurrence was detected at follow-up. Neurologic function completely recovered in
      all 12 patients from 2 to 12 weeks after surgery. The anterior bone graft fused
      and shaped well in all seven patients, and allograft bone block for lamina repair
      also achieved complete fusion in the remaining five patients. The internal
      fixator was removed at 3 to 5 years (average 4.1 years) after initial operation
      in six patients. No deformity, including scoliosis and kyphosis, has been
      identified during follow-up period in both procedures. CONCLUSIONS: For spinal
      LCH patients, neurologic deficit is a main indication for operative treatment to
      prevent permanent and serious consequences. Surgery provides an opportunity for
      rapid recovery of neurologic function. Both combined and single-stage posterior
      approaches based on pedicle screw instrumentation techniques are similarly
      effective in relieving neurologic compression. However, single-stage posterior
      approach is more favorable with less complications, and preserving involved
      vertebral body is not a latent hazard of recurrence.

PMID- 24035732
TI  - Non-functioning pituitary tumors: 2012 update.
AB  - Non-functioning pituitary adenomas are the most common pituitary macroadenomas in
      adults, accounting for approximately 14%-28% of all clinically relevant pituitary
      tumors. They are a heterogeneous group of tumors that cause symptoms by
      compression and/or hormone deficiencies. The possibility of tumor growth is
      increased in macroadenomas and solid tumors as compared to microadenomas and
      cystic tumors. Diagnosis is based on imaging procedures (magnetic resonance
      imaging), but there are studies reporting promising potential biomarkers.
      Transsphenoidal surgery remains the first therapeutic option for large tumors
      with compressive symptoms. There is no evidence that endoscopic procedures
      improve outcomes, but they decrease morbidity. There is no unanimity in finding
      prognostic predictors of recurrence. Radiosurgery achieves tumor control and,
      sometimes, adenoma size reduction. Its adverse effects increase with higher doses
      and tumor sizes>4cm(3). Drug treatment is of little value. In aggressive non
      functioning tumors, temozolomide (TMZ) may be used with caution because no
      controlled studies are available. TMZ achieves tumor control in 38%-40% of
      aggressive non-functioning tumors. The optimal treatment regimen and duration
      have not been defined yet. Lack of response to TMZ after 3 cycles predicts for
      treatment resistance, but initial response does not ensure optimal mid or long
      term results. O6-methylguanine-DNA methyltransferase expression has a limited
      predictive value of response to treatment with TMZ in aggressive non-functioning
      tumors. It should therefore not be a determinant factor in selection of patients
      to be treated with TMZ. 

PMID- 24035733
TI  - Role of oxidative and nitrosative stress in autogenous bone grafts to the
      mandible using guided bone regeneration and a deproteinized bovine bone material.
AB  - The aim of this study was to evaluate the role of oxidative and nitrosative
      stress in autogenous bone grafts to the mandible based on immunohistochemical
      analysis. MATERIAL AND METHODS: Using a well-established sheep model autogenous
      bone grafts were harvested form the iliac bone. A combination of a Collagen
      Membrane (CM) and Deproteinized Bovine Bone Material (DBBM) was used to cover the
      bone graft (Experiment 2). This modification was compared with simple onlay bone
      grafts (Experiment 1). Immunohistochemically, the expression of specific stable
      degradation products of oxidative and nitrosative stress was compared between the
      two experimental groups. RESULTS: Specific markers for oxidative and nitrosative
      stress showed statistically significant differences in expression in the
      different experimental groups. The influence of oxidative and nitrosative stress
      on osteoblasts (OB), osteoclasts (OC), and osteocytes (OCy) was analysed.
      Experiment 2 showed increased expression of markers in OB and decreased
      expression in OC. CONCLUSIONS: Taking the result of this study and reports from
      the literature into consideration grafts in Experiment 2 showed less resorption
      and atrophy, higher activity of OB and inhibition of OC, and less expression of
      Reactive Oxygen and Nitrogen Species (RONS) as markers of oxidative stress within
      the graft. These data illustrate the improved remodelling processes in grafts
      using CM and DBBM.

PMID- 24035734
TI  - Barriers to early pediatric cochlear implantation.
AB  - OBJECTIVES: Universal newborn hearing screening has significantly improved the
      ability to identify patients with congenital sensorineural hearing loss (SNHL),
      which results in earlier treatment and better hearing and development outcomes.
      It is recommended that patients born with SNHL who meet criteria receive cochlear
      implants (CIs) by a target age of 12 months, however many children are being
      implanted at an older age. This study aims to describe populations of pre-lingual
      patients with SNHL that are at risk for delayed implantation and to identify and
      analyze barriers that cause this delay. METHODS: Charts of patients receiving a
      CI between January 2008 and June 2012 at a tertiary care cochlear implant center
      were reviewed retrospectively. We looked at patient demographics, age at hearing
      loss diagnosis, age at implantation, and etiology of hearing loss. Barriers to
      implantation were identified through surveys completed by team members. RESULTS:
      Fifty-seven CI recipients were identified of which 42 were in patients with pre
      lingual SNHL. SNHL etiology included: cochlear dysplasia (18%), GJB2/GJB6 (17%),
      acquired (10%) extreme prematurity (9%), and idiopathic (46%). The median age of
      SNHL diagnosis for pre-lingual patients was 15 months. Compared to private
      insurance, public insurance status was associated with SNHL diagnosis at a
      significantly later median age (20.0 vs. 4.0 months, p=0.024), and with a
      significantly longer median interval from diagnosis to implantation (25.5 vs.
      11.0 months, p=0.029). While cochlear implant team members identified delayed
      insurance approval and medical comorbidities as reasons for delayed implantation,
      the most significant factor identified was parental, with delayed/missed
      appointments or reluctance for evaluations or surgery. CONCLUSION: 52% of
      patients with pre-lingual SNHL that met criteria for CI were implanted more than
      12 months after diagnosis. Having public or no insurance was significantly
      associated with delayed implantation. Parental barriers were most common factors
      cited for delays in implantation. Overcoming these delays necessitates
      appropriate identification of at risk patients and creating a system to educate
      families and chaperone them through the process.

PMID- 24035735
TI  - Effect of tracheostomy timing in premature infants.
AB  - OBJECTIVE: To examine if timing of tracheostomy placement in premature infants
      affects the rates of decannulation and length of time required for mechanical
      ventilatory support. MATERIALS AND METHODS: Consecutive case series with chart
      review of premature patients born at a gestational age of 36 weeks or less at a
      tertiary-care, academic children's hospital who underwent tracheostomy placement
      between July 1, 2007 and December 31, 2010 for failure to extubate and chronic
      lung disease of prematurity. Last follow-up data reviewed was January 1, 2013.
      RESULTS: 43 patients were identified. 32 patients (74.4%) were able to be weaned
      from mechanical ventilation by the end of follow-up period, and the average time
      that elapsed between tracheostomy placement and weaning from mechanical
      ventilator support was 17.9 months. 19 patients (44.2%) were able to be
      decannulated, and of those patients, the amount of time between tracheostomy
      placement and decannulation was 27.9 months. No statistical significance was
      found in the relationship between tracheostomy timing placement and ability to
      wean from mechanical ventilator support or decannulate. For those patients able
      to wean from mechanical ventilator support and get decannulated, no difference in
      the amount of time and tracheostomy timing was found. Earlier premature patients
      tended to undergo tracheostomy later in life. CONCLUSIONS: Decisions regarding
      tracheostomy placement should be individualized. We were unable to detect a
      relationship between tracheostomy timing and the ability or duration for
      premature infants with chronic lung disease of prematurity to wean from
      mechanical ventilator support or successfully decannulate.

PMID- 24035738
TI  - Chronic cholestasis in a 20-year-old young man: a case of idiopathic adulthood
      ductopenia.

PMID- 24035737
TI  - Hunting for necrosis in the shadows of intravascular ultrasound.
AB  - Coronary artery disease leads to failure of coronary circulation secondary to
      accumulation of atherosclerotic plaques. In adjunction to primary imaging of such
      vascular plaques using coronary angiography or alternatively magnetic resonance
      imaging, intravascular ultrasound (IVUS) is used predominantly for diagnosis and
      reporting of their vulnerability. In addition to plaque burden estimation,
      necrosis detection is an important aspect in reporting of IVUS. Since necrotic
      regions generally appear as hypoechic, with speckle appearance in these regions
      resembling true shadows or severe signal dropout regions, it contributes to
      variability in diagnosis. This dilemma in clinical assessment of necrosis imaged
      with IVUS is addressed in this work. In our approach, fidelity of the
      backscattered ultrasonic signal received by the imaging transducer is initially
      estimated. This is followed by identification of true necrosis using statistical
      physics of ultrasonic backscattering. A random forest machine learning framework
      is used for the purpose of learning the parameter space defining ultrasonic
      backscattering distributions related to necrotic regions and discriminating it
      from non-necrotic shadows. Evidence of hunting down true necrosis in shadows of
      intravascular ultrasound is presented with ex vivo experiments along with cross
      validation using ground truth obtained from histology. Nevertheless, in some rare
      cases necrosis is marginally over-estimated, primarily on account of non-reliable
      statistics estimation. This limitation is due to sparse spatial sampling between
      neighboring scan-lines at location far from the transducer. We suggest
      considering the geometrical location of detected necrosis together with estimated
      signal confidence during clinical decision making in view of such limitation. 

PMID- 24035736
TI  - [Maternal mortality in France, 2007-2009].
AB  - To monitor the maternal mortality which is an indicator of the quality of
      obstetric and intensive care, France has a specific approach since 1996. Recently
      linkages have been introduced to improve the inclusion of cases. Here are the
      results for the 2007 to 2009 period. The identification of the pregnancy
      associated deaths is lying on different data bases that are medical causes of
      death, birth register and hospital discharges. To document the cases,
      confidential enquiries are conducted by two assessors on the field; a committee
      of medical experts analyses the documents, select the underlying cause and assess
      the quality of health care. Two hundred and fifty-four obstetric deaths were
      identified from 2007 to 2009 giving the maternal mortality ratio (MMR) of 10.3
      per 100,000 births. The maternal age and nationality, the region of deaths are
      associated to the MMR. The haemorrhages are the leading cause but their ratio is
      1.9 versus 2.5 previously; this decrease results from the postpartum haemorrhage
      by uterine atony going down. The suboptimal care are still frequent (60%) but
      slightly less than before. The linkage method should be pursued. Maternal
      mortality is rather stable in France. We may reach more reduction as deaths due
      to atony decreased as suboptimal care did.

PMID- 24035739
TI  - Evolutionarily conserved CLE peptide signaling in plant development, symbiosis,
      and parasitism.
AB  - Small polypeptides are widely used as signaling molecules in cell-to-cell
      communication in animals and plants. The CLAVATA3/EMBRYO SURROUNDING REGION
      RELATED (CLE) gene family is composed of numerous genes that contain conserved
      CLE domains in various plant species and plant-parasitic nematodes. Here, we
      review recent progress in our understanding of CLE signaling during stem cell
      maintenance in Arabidopsis and grasses. We also summarize the roles of CLE
      signaling in the legume-Rhizobium symbiosis and infection by plant-parasitic
      nematodes. CLE signaling is important for diverse aspects of cell-to-cell
      signaling and long-distance communication, which are critical for survival, and
      the basic components of the CLE signaling pathway are evolutionarily conserved in
      both plants and animals. 

PMID- 24035740
TI  - The nucleus basalis of Meynert: a new target for deep brain stimulation in
      dementia?
AB  - Dementia is a major cause of disability amongst the elderly and represents a
      serious global health issue. Current treatments for dementia are limited; at best
      they provide inadequate symptomatic relief. In contrast, there are a plethora of
      approaches that provide symptomatic relief for abnormalities of movement
      including surgical approaches. Deep brain stimulation has been used successfully
      to directly alter processing in neural networks and thereby improve movement
      functions. Here we describe the anatomy, intrinsic organization and connectivity
      of the cholinergic nucleus basalis of Meynert, a basal forebrain structure
      implicated in cognitive functions including memory, attention, arousal and
      perception. A significant body of evidence suggests that degeneration of the
      nucleus and its cortical projections underlies the cognitive decline seen in
      dementia. We review this evidence and postulate that deep brain stimulation to
      this nucleus may be able to improve specific cognitive functions. This could
      represent a novel treatment strategy for some dementias in carefully selected
      individuals. Controlled trials of deep brain stimulation of the nucleus basalis
      of Meynert for Parkinson's disease dementia and Alzheimer's disease are required
      to evaluate potential efficacy and the mechanisms of possible cognitive changes. 

PMID- 24035741
TI  - Neural substrates underlying effort computation in schizophrenia.
AB  - The lack of initiative, drive or effort in patients with schizophrenia is linked
      to marked functional impairments. However, our assessment of effort and
      motivation is crude, relying on clinical rating scales based largely on patient
      recall. In order to better understand the neurobiology of effort in
      schizophrenia, we need more rigorous measurements of this construct. In the
      behavioural neuroscience literature, decades of work has been carried out
      developing various paradigms to examine the neural underpinnings of an animal's
      willingness to expend effort for a reward. Here, we shall review this literature
      on the nature of paradigms used in rodents to assess effort, as well as those
      used in humans. Next, the neurobiology of these effort-based decisions will be
      discussed. We shall then review what is known about effort in schizophrenia, and
      what might be inferred from experiments done in other human populations. Lastly,
      we shall discuss future directions of research that may assist in shedding light
      on the neurobiology of effort cost computations in schizophrenia. 

PMID- 24035742
TI  - Inactivation of human myeloperoxidase by hydrogen peroxide.
AB  - Human myeloperoxidase (MPO) uses hydrogen peroxide generated by the oxidative
      burst of neutrophils to produce an array of antimicrobial oxidants. During this
      process MPO is irreversibly inactivated. This study focused on the unknown role
      of hydrogen peroxide in this process. When treated with low concentrations of
      H2O2 in the absence of reducing substrates, there was a rapid loss of up to 35%
      of its peroxidase activity. Inactivation is proposed to occur via oxidation
      reactions of Compound I with the prosthetic group or amino acid residues. At
      higher concentrations hydrogen peroxide acts as a suicide substrate with a rate
      constant of inactivation of 3.9 * 10(-3) s(-1). Treatment of MPO with high H2O2
      concentrations resulted in complete inactivation, Compound III formation,
      destruction of the heme groups, release of their iron, and detachment of the
      small polypeptide chain of MPO. Ten of the protein's methionine residues were
      oxidized and the thermal stability of the protein decreased. Inactivation by high
      concentrations of H2O2 is proposed to occur via the generation of reactive
      oxidants when H2O2 reacts with Compound III. These mechanisms of inactivation may
      occur inside neutrophil phagosomes when reducing substrates for MPO become
      limiting and could be exploited when designing pharmacological inhibitors.

PMID- 24035743
TI  - A specific interdomain interaction preserves the structural and binding
      properties of the ModA protein from the phytopathogen Xanthomonas citri domain
      interaction and transport in ModA.
AB  - The periplasmic-binding proteins in ATP-binding cassette systems (ABC
      Transporters) are responsible for the capture and delivery of ligands to their
      specific transporters, triggering a series of ATP-driven conformational changes
      that leads to the transport of the ligand. Structurally consisting of two lobes,
      the proteins change conformation after interaction with the ligand. The structure
      of the molybdate-binding protein (ModA) from Xanthomonas citri, bound to
      molybdate, was previously solved by our group and an interdomain interaction,
      mediated by a salt bridge between K127 and D59, apparently supports the binding
      properties and keeps the domains closed. To determinate the importance of this
      interaction, we built two ModA mutants, K127S and D59A, and analysed their
      functional and structural properties. Based on a set of spectroscopic
      experiments, crystallisation trials, structure determination and molecular
      dynamics (MD) simulations, we showed that the salt bridge is essential to
      maintain the structure and binding properties. Additionally, the MD simulations
      revealed that this mutant adopted a more compact structure that packed down the
      ligand-binding pocket. From the closed bound to open structure, the positioning
      of the helices forming the dipole and the salt bridge are essential to induce an
      intermediate state.

PMID- 24035744
TI  - Evaluation of propargyl alcohol toxicity and carcinogenicity in F344/N rats and
      B6C3F1/N mice following whole-body inhalation exposure.
AB  - Propargyl alcohol (PA) is a high production volume chemical used in synthesis of
      many industrial chemicals and agricultural products. Despite the potential for
      prolonged or accidental exposure to PA in industrial settings, the toxicity
      potential of PA was not well characterized. To address the knowledge gaps
      relevant to the toxicity profile of PA, the National Toxicology Program (NTP)
      conducted 2-week, 14-week and 2-year studies in male and female F344/N rats and
      B6C3F1/N mice. For the 2-week inhalation study, the rats and mice were exposed to
      0, 31.3, 62.5, 125, 250 or 500ppm. Significant mortality was observed in both
      rats and mice exposed to >=125ppm of PA. The major target organ of toxicity in
      both mice and rats was the liver with exposure-related histopathological changes
      (250 and 500ppm). Based on the decreased survival in the 2-week study, the rats
      and mice were exposed to 0, 4, 8, 16, 32 or 64ppm of PA in the 14-week study. No
      treatment-related mortality was observed. Mean body weights of male (>=8ppm) and
      female mice (32 and 64ppm) were significantly decreased (7-16%).
      Histopathological changes were noted in the nasal cavity, and included
      suppurative inflammation, squamous metaplasia, hyaline droplet accumulation,
      olfactory epithelium atrophy, and necrosis. In the 2-year inhalation studies, the
      rats were exposed to 0, 16, 32 and 64ppm of PA and the mice were exposed to 0, 8,
      16 and 32ppm of PA. Survival of male rats was significantly reduced (32 and
      64ppm). Mean body weights of 64ppm male rats were significantly decreased
      relative to the controls. Both mice and rats showed a spectrum of non-neoplastic
      changes in the nose. Increased neoplastic incidences of nasal
      respiratory/transitional epithelial adenoma were observed in both rats and mice.
      The incidence of mononuclear cell leukemia was significantly increased in male
      rats and was considered to be treatment-related. In conclusion, the key findings
      from this study indicated that the nose was the primary target organ of toxicity
      for PA. Long term inhalation exposure to PA led to nonneoplastic changes in the
      nose, and increased incidences of respiratory/transitional epithelial adenomas in
      both mice and rats. Increased incidences of harderian gland adenoma may also have
      been related to exposure to PA in male mice. 

PMID- 24035745
TI  - A biological continuum based approach for efficient clinical classification.
AB  - Clinical feature selection problem is the task of selecting and identifying a
      subset of informative clinical features that are useful for promoting accurate
      clinical diagnosis. This is a significant task of pragmatic value in the clinical
      settings as each clinical test is associated with a different financial cost,
      diagnostic value, and risk for obtaining the measurement. Moreover, with
      continual introduction of new clinical features, the need to repeat the feature
      selection task can be very time consuming. Therefore to address this issue, we
      propose a novel feature selection technique for diagnosis of myocardial
      infarction - one of the leading causes of morbidity and mortality in many high
      income countries. This method adopts the conceptual framework of biological
      continuum, the optimization capability of genetic algorithm for performing
      feature selection and the classification ability of support vector machine.
      Together, a network of clinical risk factors, called the biological continuum
      based etiological network (BCEN), was constructed. Evaluation of the proposed
      methods was carried out using the cardiovascular heart study (CHS) dataset.
      Results demonstrate a significant speedup of 4.73-fold can be achieved for the
      development of MI classification model. The key advantage of this methodology is
      the provision of a reusable (feature subset) paradigm for efficient development
      of up-to-date and efficacious clinical classification models. 

PMID- 24035746
TI  - Olfactory responses of the antennal trichoid sensilla to chemical repellents in
      the mosquito, Culex quinquefasciatus.
AB  - Insect repellents are widely used to protect against insect bites and thus
      prevent allergic reaction and the spread of disease. To gain insight into the
      mosquito's response to chemicals repellents, we investigated the interaction
      between the olfactory system of the mosquito Culex quinquefasciatus Say and
      chemical repellents using single sensillum recording. The interactions of 50
      repellent chemicals with olfactory receptor neurons were measured in six
      different types of mosquito sensilla: long sharp trichoid (LST), short sharp
      trichoid (SST), short blunt trichoid I (SBT-I), short blunt trichoid II (SBT-II),
      short blunt trichoid-curved (SBT-C), and grooved peg (GP). A single olfactory
      neuron reacted to the chemical repellents in each of the sensilla except for SBT
      I and SBT-II, where two neurons were involved. Other than LST and GP, which
      showed no or very weak responses to the repellents tested, all the sensilla
      showed significant excitatory responses to certain types of repellents. Terpene
      derived chemicals such as eucalyptol, alpha-pinene, and camphor, stimulated
      olfactory receptor neurons in a dose-dependent manner and mosquitoes responded
      more strongly to terpene-derived chemical repellents than to non-terpene-derived
      chemicals such as dimethyl phthalate. Mosquitoes also exhibited a similar
      response to stereoisomers of chemicals such as (-)-beta-pinene versus (+)-beta
      pinene, and (-)-menthone versus (+)-menthone. This study not only demonstrates
      the effects of chemical repellents on the mosquito olfactory system but also
      provides important information that will assist those screening new mosquito
      repellents and designing new mosquito control agents. 

PMID- 24035747
TI  - Protaphorura tricampata, a euedaphic and highly permeable springtail that can
      sustain activity by osmoregulation during extreme drought.
AB  - We have investigated drought physiology of soil dwelling springtails since water
      availability is a key environmental factor governing their performance, and
      predictions of climate change suggest increased frequency and intensity of summer
      droughts. Here we show in field and laboratory experiments that the typical
      euedaphic springtail, Protaphorura tricampata, can survive extreme drought and
      remain active in soils where the water potential is much lower than equivalent to
      normal osmotic pressure of springtails. Euedaphic springtails (i.e. species
      living in deeper soil layers) have an extraordinary ability to up-regulate
      osmotic pressure of body fluids and prevent water loss in soils where the water
      potential has dropped to well below the permanent wilting percentage of plants.
      The ability to regulate osmotic pressure of body fluids is based on accumulation
      of compatible osmolytes such as sugars and free amino acids. Alanine was the most
      important osmolyte in P. tricampata and accumulated to concentrations of about
      300MUmolg(-1) dry weight. It is suggested that alanine also serves as a non-toxic
      storage of ammonia during drought periods where the normal urine production is
      hampered. The results presented here show, contrary to convention, that high
      cuticular permeability is not necessarily accompanied by poor drought tolerance,
      and is not a good predictor of drought susceptibility. 

PMID- 24035748
TI  - Non-swarming grasshoppers exhibit density-dependent phenotypic plasticity
      reminiscent of swarming locusts.
AB  - Locusts are well known for exhibiting an extreme form of density-dependent
      phenotypic plasticity known as locust phase polyphenism. At low density, locust
      nymphs are cryptically colored and shy, but at high density they transform into
      conspicuously colored and gregarious individuals. Most of what we know about
      locust phase polyphenism come from the study of the desert locust Schistocerca
      gregaria (Forskal), which is a devastating pest species affecting many countries
      in North Africa and the Middle East. The desert locust belongs to the grasshopper
      genus Schistocerca Stal, which includes mostly non-swarming, sedentary species.
      Recent phylogenetic studies suggest that the desert locust is the earliest
      branching lineage within Schistocerca, which raises a possibility that the
      presence of density-dependent phenotypic plasticity may be a plesiomorphic trait
      for the whole genus. In order to test this idea, we have quantified the effect of
      rearing density in terms of the resulting behavior, color, and morphology in two
      non-swarming Schistocerca species native to Florida. When reared in both isolated
      and crowded conditions, the two non-swarming species, Schistocerca americana
      (Drury) and Schistocerca serialis cubense (Saussure) clearly exhibited plastic
      reaction norms in all traits measured, which were reminiscent of the desert
      locust. Specifically, we found that both species were more active and more
      attracted to each other when reared in a crowded condition than in isolation.
      They were mainly bright green in color when isolated, but developed strong black
      patterns and conspicuous background colors when crowded. We found a strong effect
      of rearing density in terms of size. There were also more mechanoreceptor hairs
      on the outer face of the hind femora in the crowded nymphs in both species.
      Although both species responded similarly, there were some clear species-specific
      differences in terms of color and behavior. Furthermore, we compare and contrast
      our findings with those on the desert locust and other relevant studies. We
      attribute the presence of density-dependent phenotypic plasticity in the non
      swarming Schistocerca species to phylogenetic conservatism, but there may be a
      possible role of local adaptation in further shaping the ultimate expressions of
      plasticity. 

PMID- 24035749
TI  - Expression analysis and molecular characterization of aquaporins in Rhodnius
      prolixus.
AB  - Aquaporins (AQPs) are water channels responsible for transport of water and, in
      some cases, transport of small solutes such as urea and glycerol across lipid
      bilayer membranes. Hematophagous insects, such as Rhodnius prolixus, ingest large
      volumes of fluid and must rapidly eliminate the excess of water and salts from
      the blood meal within the gut. In order to deal with this increase in body fluid
      volume, a hormone-controlled diuresis is activated, during which a high rate of
      water and salt absorption occurs across the anterior midgut, followed by
      secretion of water and salts by the Malpighian tubules (MTs). Previously, one
      member of the MIP family (major intrinsic protein that includes the AQP family)
      was identified in the MTs of R. prolixus, and named RpMIP. We have described here
      that the RpMIP gene has different variants, and is present in tissues other than
      MTs. In addition, we have characterized a new AQP (RhoprAQP1) found in different
      tissues of R. prolixus. The expression of these transcripts in unfed insects as
      well as blood fed insects was evaluated using real-time quantitative PCR.
      Molecular models of the predicted proteins were constructed and the
      characteristics of their pores evaluated. A yeast complementation assay was used
      to validate that the products of these transcripts were bona fide AQPs. Both
      RhoprAQP1 and RhoprMIP-A were capable of transporting water whereas RhoprMIP-A
      was also capable of transporting H2O2. Taken together, these analyses suggest
      that RhoprMIP is probably an aquaglyceroporin, while RhoprAQP1 appears to be a
      strict aquaporin that transports only water. 

PMID- 24035750
TI  - Fire ant alarm pheromone and venom alkaloids act in concert to attract parasitic
      phorid flies, Pseudacteon spp.
AB  - Pseudacteon tricuspis, Pseudacteon obtusus and Pseudacteon curvatus are three
      species of parasitic phorid flies (Diptera: Phoridae), which have been introduced
      as classical biological control agents of imported, Solenopsis fire ants
      (Hymenoptera: Formicidae) in the southern USA. Previous studies demonstrated the
      behavioral response of P. tricuspis to the venom alkaloids and alarm pheromone of
      the fire ant, S. invicta. In the present study, we compared the responses of P.
      tricuspis, P. obtusus and P. curvatus to Solenopsis invicta alarm pheromone,
      venom alkaloids, or a mixture of both chemicals in four-choice olfactometer
      bioassays. The main hypothesis tested was that the fire ant alarm pheromone and
      venom alkaloids act in concert to attract Pseudacteon phorid flies. Both sexes of
      all three Pseudacteon species were attracted to low doses of the fire ant alarm
      pheromone or venom alkaloids (i.e. 1 ant worker equivalent) alone. However, the
      flies were significantly more attracted to a mixture of both chemicals (i.e., 1:1
      mixture of alarm pheromone+alkaloids) than to either chemical. The results
      suggest an additive rather than a synergistic effect of combining both chemicals.
      Comparing the fly species, P. tricuspis showed relatively greater attraction to
      cis alkaloids, whereas the alkaloid mixture (cis+trans) was preferred by P.
      obtusus and P. curvatus. In general, no key sexual differences were recorded,
      although females of P. tricuspis and P. obtusus showed slightly higher response
      than conspecific males to lower doses of the alarm pheromone. The ecological
      significance of these findings is discussed, and a host location model is
      proposed for parasitic phorid flies involving the use of fire ant alarm pheromone
      and venom alkaloids as long range and short range attractants, respectively. 

PMID- 24035751
TI  - Field trial tests of FKC vaccines against RSIV genotype Megalocytivirus in cage
      cultured mandarin fish (Siniperca chuatsi) in an inland reservoir.
AB  - Megalocytiviruses are one of the most important causative agents in finfish
      industry in China, Japan and South East Asia. The viruses are mainly composed of
      ISKNV, RSIV and TRBIV genotypes. Among them, ISKNV genotype isolate is the most
      important causative agent in mandarin fish industry in South China. Since its
      first occurrence in mid-1990s in China, no effective drug has been developed to
      prevent and control this virus until our recent work. In this study, unusual RSIV
      genotype Megalocytivirus was validated as the causative agent in natural mass
      mortality of cage-cultured mandarin fish in an inland reservoir. One isolate was
      obtained using MFF-1 cells from natural mass mortality of mandarin fish and
      designated as Megalocyti-LJ2012. Based on two previous megalocytiviral isolates,
      formalin-killed cell (FKC) vaccines were prepared to immunize 2000 and 9000 cage
      cultured mandarin in October 2011 and August 2012, respectively. As results,
      greater than 70% protective effects were observed in vaccination group in both
      individual field tests. Adjuvant-emulsified FKC vaccine provided even greater
      than 99% protective effect (N = 1000). In contrast, almost all fish died in non
      vaccination group (N = 1000). Immuno-protection test under laboratory condition
      showed that 100% relative percent survival was obtained in surviving fish from
      vaccination group after challenge with Megalocyti-LJ2012 at 4 months post
      vaccination. Taken together, the present study shows that FKC vaccine is also
      efficient in preventing RSIV genotype Megalocytivirus in cage-cultured mandarin
      fish in two field tests.

PMID- 24035752
TI  - Vibrio anguillarum bacterin uptake via the gills of Japanese flounder and
      subsequent immune responses.
AB  - The mucosal surfaces of fish allow for the introduction of foreign substances,
      including antigens, from the surrounding environment. In this study, uptake of
      Vibrio anguillarum J-O-3 serotype bacterin by Japanese flounder, and the
      subsequent immune responses were investigated. Immunohistochemistry revealed that
      the bacterin was taken up through the epithelial cells of gills. The
      transcription levels of inflammatory cytokines such as interleukin (IL)-1beta, IL
      6 and tumor necrosis factor alpha were significantly up-regulated in the gills at
      3 days following exposure to the bacterin. There was also a corresponding
      increase in IL-8 receptor, CD4-1, CD4-2 and CD8alpha transcript levels in the
      gills. Our findings suggest that the gills play a major role in the uptake of V.
      anguillarum bacterin and induction of inflammation, which results in an
      activation of the adaptive immune response in teleost fish. 

PMID- 24035753
TI  - Perfluorooctanoic acid induces apoptosis through the p53-dependent mitochondrial
      pathway in human hepatic cells: a proteomic study.
AB  - Perfluorooctanoic acid (PFOA) is one of the most commonly used perfluorinated
      compounds, and exposure to it has been associated with a number of adverse health
      effects. However, the molecular mechanisms involved in PFOA toxicity are still
      not well characterized. In the present study, flow cytometry analysis revealed
      that PFOA induced oxidative stress, cell cycle arrest and apoptosis in human non
      tumor hepatic cells (L-02). Furthermore, we investigated the alterations in
      protein profile within L-02 cells exposed to PFOA, aiming to explore the
      mechanisms underlying PFOA hepatotoxicity on the proteome level. Of the 28
      proteins showing significant differential expression in response to PFOA, 24 were
      down-regulated and 4 were up-regulated. This proteomic study proposed that the
      inhibition of some proteins, including GRP78, HSP27, CTSD and hnRNPC may be
      involved in the activation of p53, which consequently triggered the apoptotic
      process in L-02 cells. Induction of apoptosis via the p53-dependent mitochondrial
      pathway is further suggested as one of the key toxicological events occurring in
      L-02 cells under PFOA stress. We hope these data will shed new light on the
      molecular mechanisms responsible for PFOA-mediated toxicity in human liver cells,
      and from such studies useful biomarkers indicative of PFOA exposure could be
      developed. 

PMID- 24035754
TI  - Desmopressin improves intestinal functional capillary density and decreases
      leukocyte activation in experimental endotoxemia.
AB  - BACKGROUND: Blood flow to the intestine is decreased in sepsis in favor of vital
      organs resulting in ischemic damage of the gut mucosa. Once the mucosa is
      damaged, increased translocation of intestinal bacteria to the systemic
      circulation may occur. This in turn aggravates the inflammatory response
      contributing to the development of multi-organ failure. Desmopressin is a
      synthetic analog of vasopressin, an anti-diuretic hormone which has been shown to
      induce vasodilation and is thought to be implicated in immunomodulation. In this
      study, we investigate the effects of desmopressin on the intestinal
      microcirculation during sepsis in an experimental endotoxemia model in rats using
      intravital microscopy. In addition, we investigate the effects of desmopressin on
      systemic inflammation. METHODS: Forty Lewis rats were subdivided into four
      groups, where rats received intravenous saline (control), desmopressin
      (1MUg/kg/ml), lipopolysaccharide (5mg/kg) or lipopolysaccharide followed by
      desmopressin. Inflammatory response was assessed by quantifying the number of
      temporary and firmly adherent leukocytes in submucosal venules. Capillary
      perfusion was determined by assessing the number of functional, non-functional
      and dysfunctional capillaries in the intestinal wall layers (muscularis
      longitudinalis, muscularis circularis and mucosa). Additionally, inflammatory
      cytokine levels were determined by multiplex assays. RESULTS: The number of
      firmly adhering leukocytes in V1 venules of rats receiving lipopolysaccharide and
      treated with desmopressin was significantly reduced compared to
      lipopolysaccharide only group (LPS: 259+/-25.7 vs. LPS+DDAVP: 203+/-17.2;
      n/mm(2); p<0.05). Additionally, desmopressin treatment improved impaired
      intestinal microcirculation by improving functional capillary density following
      lipopolysaccharide administration in all examined layers of the intestinal wall.
      We also observed a significant decrease in TNF-alpha levels in rats which
      received desmopressin in endotoxemia compared to untreated rats (LPS: 383+/-64.2;
      LPS+DDAVP: 261.3+/-22; pg/ml; p<0.05). CONCLUSION: Desmopressin administration
      improved intestinal capillary perfusion and reduced inflammatory response in rat
      endotoxemia.

PMID- 24035755
TI  - Hydrogen sulphide vasodilates human pulmonary arteries: a possible role in
      pulmonary hypertension?
AB  - INTRODUCTION: Acute rises in pulmonary artery pressures are associated with a
      significant mortality and morbidity due to the significant strain on the right
      ventricle. Although hydrogen sulphide (H2S) has been studied for its potential
      role in the systemic circulation, little is known of its effects on the pulmonary
      circulation in humans. We studied the effect of H2S at both the human isolated
      pulmonary arterial level as well as the human isolated perfused lung level.
      METHODS: Human lobar pulmonary artery rings (n=12) and lobes (n=3) were obtained
      from resections for patients with bronchial carcinoma. Pre-constricted fresh
      rings were mounted in organ baths containing normoxic Krebs solution and
      subsequently exposed to hydrogen sulphide whilst tension was recorded. Isolated
      perfused human lung models consisted of lobes ventilated via a bronchial cannula
      and perfused with Krebs via a pulmonary artery cannula; hydrogen sulphide was
      added to the perfusate and the resulting pulmonary artery and bronchial pressures
      were recorded. RESULTS: We found that 500MUM H2S caused a mean dilation of 42.3%
      (+/-5.4) from the pre-constricted tension (p<0.005) in isolated arterial rings.
      In addition, 500MUM H2S caused a 17.73% (3.52) reduction in pulmonary artery
      pressures (p<0.05). Furthermore, we found that 500MUM H2S caused a 14.9% (6.01)
      reduction in bronchial airway pressures (p<0.05). CONCLUSIONS: We have shown that
      H2S is a potent vasodilator of human pulmonary arteries and is a significant anti
      hypertensive for pulmonary artery pressures. Our results indicate that this
      therapeutic potential should be further evaluated in clinical trials.

PMID- 24035756
TI  - Change in inflammatory cytokine profiles after transarterial chemotherapy in
      patients with hepatocellular carcinoma.
AB  - BACKGROUND: Alterations in cytokine profiles after chemotherapy can affect the
      outcomes of cancer patients. This study evaluated the clinical implications of
      cytokine changes after transarterial chemo-embolization (TACE) in patients with
      hepatocellular carcinoma (HCC). METHODS: Cytometric bead immunoassays were used
      to simultaneously measure 13 cytokines (interleukin [IL]-12p70, interferon-gamma,
      IL-17A, IL-2, IL-10, IL-9, IL-22, IL-6, IL-13, IL-4, IL-5, IL-1beta, and tumor
      necrosis factor-alpha) in the sera of 83 patients with HCC and 33 healthy
      controls. Cytokines were serially monitored at baseline, on days 3 and 7, and
      2months after TACE in 63 evaluable patients. RESULTS: Serum levels of IL-5, IL-6,
      and IL-17A were higher in patients with HCC than in healthy controls, whereas IL
      1beta and IL-22 levels were lower in patients with HCC. Of the cytokines
      measured, only the IL-6 level showed a significant positive correlation with both
      tumor size and Child-Pugh score. The Child-Pugh B/C group had higher IL-6 and
      lower IL-22 levels at baseline and exhibited relatively minor changes in cytokine
      levels compared with the Child-Pugh A group. We observed diverse changing
      patterns of individual cytokines on each date tested, with IL-6 and IL-22
      increasing early after TACE. Particularly, IL-6 reached a peak on day 3 and
      finally decreasing on and after day 7. IL-4, IL-5, and IL-10, on the other hand,
      increased during the late phase, 2months after TACE. Patients with larger tumors
      (>5cm) showed a transient but significant early-phase increase in IL-6 levels
      coupled with severe post-TACE hepatitis, as well as late-phase increases in IL-4,
      IL-5, and IL-10 levels after TACE. CONCLUSIONS: TACE induces changes in levels of
      multiple cytokines. Distinct panels of cytokine changes are not uniform, and are
      influenced by treatment-induced inflammation, underlying liver function, and HCC
      stage. Early-phase increases in IL-6 after TACE reflect acute-phase responses and
      are partly associated with post-treatment hepatitis, while late-phase increases
      in Th2 cytokine profiles suggest immune suppression in patients with large
      tumors.

PMID- 24035757
TI  - Fracture non-union: who is at risk?

PMID- 24035758
TI  - The utility of laparoscopic evaluation of the parietal peritoneum in the
      management of anterior abdominal stab wounds.
AB  - BACKGROUND: Trauma centres vary in their approaches to managing stable patients
      with anterior abdominal stab wounds (AASWs), with no approach yet proven
      superior. We sought to evaluate the performance of screening laparoscopy (i.e.,
      parietal peritoneal penetration or not) in determining which patients should
      undergo laparotomy. METHODS: We conducted a retrospective case series study,
      including all patients with an AASW who presented to U.C. Davis Medical Center
      from January 2003 through March 2009. We collected data from medical records
      using a standardised, pre-tested instrument. Among laparoscopically screened
      cases, we determined the test characteristics of peritoneal penetration for
      detecting intra-abdominal injury. We sub-classified injuries as "requiring
      treatment" (e.g., full-thickness enterotomy or active haemorrhage) or not.
      RESULTS: Of 358 patients with AASWs, 163 underwent screening laparoscopy. Seventy
      eight of the 163 (48%) had no peritoneal penetration and six (4%) had peritoneal
      penetration but a low-risk wound; none of these 84 underwent laparotomy nor had a
      missed injury. Of 79 patients with peritoneal penetration who underwent
      laparotomy, 61 had an intra-abdominal injury, of whom 42 were treated
      intraoperatively. Among these 42, 30 had an injury "requiring treatment." The PPV
      of peritoneal penetration for an injury requiring treatment was 38% (30/79) (95%
      CI 27-50%), NPV 100% (84/84) (95% CI 95-100%), sensitivity 100% (30/30) (95% CI
      88-100%), and specificity 63% (84/133) (95% CI 54-71%). The negative and positive
      likelihood ratios were 0 (95% CI 0-0.4) and 2.7 (95% CI 2.2-3.4), respectively.
      CONCLUSIONS: Screening laparoscopic evaluation of the parietal peritoneum results
      in a negligible rate of missed injury and an approximately 40% rate of finding an
      injury requiring treatment.

PMID- 24035760
TI  - Learning classification models from multiple experts.
AB  - Building classification models from clinical data using machine learning methods
      often relies on labeling of patient examples by human experts. Standard machine
      learning framework assumes the labels are assigned by a homogeneous process.
      However, in reality the labels may come from multiple experts and it may be
      difficult to obtain a set of class labels everybody agrees on; it is not uncommon
      that different experts have different subjective opinions on how a specific
      patient example should be classified. In this work we propose and study a new
      multi-expert learning framework that assumes the class labels are provided by
      multiple experts and that these experts may differ in their class label
      assessments. The framework explicitly models different sources of disagreements
      and lets us naturally combine labels from different human experts to obtain: (1)
      a consensus classification model representing the model the group of experts
      converge to, as well as, and (2) individual expert models. We test the proposed
      framework by building a model for the problem of detection of the Heparin Induced
      Thrombocytopenia (HIT) where examples are labeled by three experts. We show that
      our framework is superior to multiple baselines (including standard machine
      learning framework in which expert differences are ignored) and that our
      framework leads to both improved consensus and individual expert models. 

PMID- 24035759
TI  - Use of proton pump inhibitors and subsequent risk of celiac disease.
AB  - BACKGROUND: The prevalence of celiac disease and the use of medications that
      inhibit acid secretion have both increased in recent decades. AIM: To explore the
      association between antisecretory medication exposure and subsequent development
      of celiac disease. METHODS: In this population-based case control study, we
      identified patients with celiac disease diagnosed at all pathology departments in
      Sweden from July 2005 through February 2008. Patients were matched by age and
      gender with up to 5 controls. We identified prior prescriptions for proton pump
      inhibitors and histamine-2 receptor antagonists in all subjects. We used
      conditional logistic regression to measure the association between these
      prescriptions and the subsequent diagnosis of celiac disease. RESULTS: Prior
      proton pump inhibitor prescription was strongly associated with celiac disease
      (OR 4.79; 95% CI 4.17-5.51). Patients prescribed both proton pump inhibitors and
      histamine-2 receptor antagonists had a higher risk of celiac disease (OR 5.96;
      95% CI 3.58-9.91) than those prescribed proton pump inhibitors alone (OR 4.91;
      95% CI 4.26-5.66) or histamine-2 receptor antagonists alone (OR 4.16; 95% CI 2.89
      5.99). CONCLUSIONS: Exposure to antisecretory medications is associated with a
      subsequent diagnosis of celiac disease. The persistence of this association after
      excluding prescriptions in the year preceding the celiac disease diagnosis
      suggests a causal relationship.

PMID- 24035761
TI  - The role of hydrolases in bacterial cell-wall growth.
AB  - Although hydrolysis is known to be as important as synthesis in the growth and
      development of the bacterial cell wall, the coupling between these processes is
      not well understood. Bond cleavage can generate deleterious pores, but may also
      be required for the incorporation of new material and for the expansion of the
      wall, highlighting the importance of mechanical forces in interpreting the
      consequences of hydrolysis in models of growth. Critically, minimal essential
      subsets of hydrolases have now been identified in several model organisms,
      enabling the reduction of genetic complexity. Recent studies in Bacillus subtilis
      have provided evidence for both the presence and absence of coupling between
      synthesis and hydrolysis during sporulation and elongation, respectively. In this
      review, we discuss strategies for dissecting the relationship between synthesis
      and hydrolysis using time-lapse imaging, biophysical measurements of cell-wall
      architecture, and computational modeling. 

PMID- 24035764
TI  - Characterization in biological traits of entomopathogenic nematodes isolated from
      North China.
AB  - In a series of bioassays, thirty-one isolates that were collected from diverse
      locations in northern China and the laboratory kept isolate Steinernema
      carpocapsae All, were compared in order to select superior isolates for
      biological control of Bradysia odoriphaga. Virulence of the isolates against B.
      odoriphaga was significantly different among nematode isolates. Tolerance of
      infective juveniles (IJs) to heat, cold, and desiccation differed significantly
      among and within species. Strains from S. carpocapsae, S. ceratophorum, S.
      longicaudum, Heterorhabditis indica, and H. bacteriophora were more heat tolerant
      than strains from S. feltiae, S. hebeiense, S. monticolum, and H. megidis.
      Heterorhabditis megidis, H. bacteriophora, and S. carpocapsae showed better cold
      tolerance than the other species. High desiccation tolerance was recorded for S.
      carpocapsae, S. hebeiense, and S. ceratophorum. The infectivity of IJ of these
      species against Galleria mellonella larvae was not significantly different
      between the treated and non-treated IJ after the nematodes had been exposed to 40
      degrees C for 2 h, -5 degrees C for 8 h or 25% glycerin for 72 h. Nematode
      survival was significantly affected by exposure time and IJ concentration when
      exposed to 40 degrees C or -5 degrees C. All nematode isolates lost their
      infectivity against G. mellonella after exposure to -5 degrees C for 16 h, except
      for H. megidis LFS10, which had a low infectivity of 3.3%. A hierarchical
      classification analysis classified the isolates in four main clusters. The fourth
      cluster, composed of 13 isolates, grouped the isolates that scored well for most
      traits.

PMID- 24035763
TI  - Dynamic construction of a coherent attentional state in a prefrontal cell
      population.
AB  - Prefrontal cortex has been proposed to show highly adaptive information coding,
      with neurons dynamically allocated to processing task-relevant information. To
      track this dynamic allocation in monkey prefrontal cortex, we used time-resolved
      measures of neural population activity in a simple case of competition between
      target (behaviorally critical) and nontarget objects in opposite visual
      hemifields. Early in processing, there were parallel responses to competing
      inputs, with neurons in each hemisphere dominated by the contralateral stimulus.
      Later, the nontarget lost control of neural activity, with emerging global
      control by the behaviorally critical target. The speed of transition reflected
      the competitive weights of different display elements, occurring most rapidly
      when relative behavioral significance was well established by training history.
      In line with adaptive coding, the results show widespread reallocation of
      prefrontal processing resources as an attentional focus is established. 

PMID- 24035762
TI  - Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required
      for neuronal circuit development.
AB  - Neuronal arborization is regulated by cell-autonomous and nonautonomous
      mechanisms including endosomal signaling via BDNF/TrkB. The endosomal Na+/H+
      exchanger 6 (NHE6) is mutated in a new autism-related disorder. NHE6 functions to
      permit proton leak from endosomes, yet the mechanisms causing disease are
      unknown. We demonstrate that loss of NHE6 results in overacidification of the
      endosomal compartment and attenuated TrkB signaling. Mouse brains with disrupted
      NHE6 display reduced axonal and dendritic branching, synapse number, and circuit
      strength. Site-directed mutagenesis shows that the proton leak function of NHE6
      is required for neuronal arborization. We find that TrkB receptor colocalizes to
      NHE6-associated endosomes. TrkB protein and phosphorylation are reduced in NHE6
      mutant neurons in response to BDNF signaling. Finally, exogenous BDNF rescues
      defects in neuronal arborization. We propose that NHE6 mutation leads to circuit
      defects that are in part due to impoverished neuronal arborization that may be
      treatable by enhanced TrkB signaling.

PMID- 24035765
TI  - [Access and use of new information and telecommunication technologies among
      teenagers at high school, health implications. JOITIC Study].
AB  - OBJECTIVE: To determine ICT accessibility and use among the adolescents attending
      High School and to analyse related factors. DESIGN: Cross-sectional multicentric
      study. SETTING: High Schools participating in the Community Health "Salut i
      Escola" Programme. PARTICIPANTS: 5,538 students from first to fourth degree at 28
      centres in the area of Barcelona. MAIN MEASUREMENTS: Self administered
      questionnaire including sociodemographic information, ICT use and accessibility.
      RESULTS: Missing answers were below 1% in all items except in school performance
      (3,13%); 48,6% were female, mean age 14years (range 11-20); 15,5% foreigners; 23%
      reported low school performance; 75,2% took extracurricular activities; 88,9%
      refers a good relationship with their parents. ICT access is homogeneously
      massive: 98% had a computer at home, 44,8% used it for two or more hours daily.
      98,6% could access Internet, 47,2% without parental control. 90% owned a mobile
      phone (83% in first grade, 95% in fourth); 45,6% owned one before 12years old.
      Girls use it for social relationships and boys for playing. 68,4% played
      videogames, 36,5% for three or more hours a week and 66,8% without parental
      control. Their use decreases with age. The ICT parental control is associated
      with better school performance. CONCLUSIONS: Our high scholars gain access to the
      ICT at younger ages and they use them in almost every aspect of their lives.
      There have been detected some gender differences in their use, as well as in the
      age of the users and between the type of school.

PMID- 24035766
TI  - [Medicine consumption in the adult population: Influence of self-medication].
AB  - OBJECTIVE: The objective of this study is to determine the factors associated
      with medicine consumption and self-consumption in Aragon (Spain) DESIGN: Cross
      sectional study from the National Health Survey 2006. SETTING: Aragon (Spain).
      PARTICIPANTS: Adult population in Aragon (Spain). MAIN MEASUREMENTS: Medicine
      consumption and the type of consumption. Demographic, health and health style
      variables were also considered. RESULTS: At least one drug was taken by the 65.1%
      of the adults in Aragon during the previous two weeks. Of this group, 11.7% were
      self-medicated. A higher frequency of consumption was observed in females and
      older people, and in those with a poor self-perceived health. People with a low
      educational level took drugs more often, but self-consumption was more frequent
      in the group with a high educational level. CONCLUSIONS: Medicine consumption and
      self-consumption in adults in Aragon is common. It is of great interest to know
      the consumption profile of these patients in order to develop specific
      interventions to reduce unnecessary consumption and to improve safety.

PMID- 24035767
TI  - [Pharmacological treatment conciliation methodology in patients with multiple
      conditions].
AB  - OBJECTIVE: To carry out a bibliographic review in order to identify the different
      methodologies used along the reconciliation process of drug therapy applicable to
      polypathological patients. DESIGN: We performed a literature review. Data sources
      The bibliographic review (February 2012) included the following databases:
      Pubmed, EMBASE, CINAHL, PsycINFO and Spanish Medical Index (IME). The different
      methodologies, identified on those databases, to measure the conciliation process
      in polypathological patients, or otherwise elderly patients or polypharmacy, were
      studied. Study selection Two hundred and seventy three articles were retrieved,
      of which 25 were selected. Data extraction Specifically: the level of care, the
      sources of information, the use of registration forms, the established time, the
      medical professional in charge and the registered variables such as errors of
      reconciliation. RESULTS: Most of studies selected when the patient was admitted
      into the hospital and after the hospital discharge of the patient. The main
      sources of information to be highlighted are: the interview and the medical
      history of the patient. An established time is not explicitly stated on most of
      them, nor the registration form is used. The main professional in charge is the
      clinical pharmacologist. Apart from the home medication, the habits of self
      medication and phytotherapy are also identified. The common errors of
      reconciliation vary from the omission of drugs to different forms of interaction
      with other medicinal products (drugs interactions). CONCLUSIONS: There is a large
      heterogeneity of methodologies used for reconciliation. There is not any work
      done on the specific figure of the polypathological patient, which precisely
      requires a standardized methodology due to its complexity and its susceptibility
      to errors of reconciliation.

PMID- 24035768
TI  - Functional outcomes associated with adaptive seating interventions in children
      and youth with wheeled mobility needs.
AB  - OBJECTIVE: To determine the parent-reported functional outcomes associated with
      adaptive seating devices for wheeled mobility devices used by young people aged 1
      to 17 years. DESIGN: Longitudinal case series. SETTING: Homes of participating
      parents. PARTICIPANTS: Parents (N=70, 63 mothers, 6 fathers, 1 grandmother) who
      had children with adaptive seating needs. INTERVENTION: Adaptive seating system
      for wheeled mobility devices. MAIN OUTCOME MEASURE: Family Impact of Assistive
      Technology Scale for Adaptive Seating (FIATS-AS). RESULTS: All parents completed
      the FIATS-AS 4 times-2 times before and 2 times after their child received a new
      adaptive seating system. Mixed-design analysis of variance did not detect
      significant mean differences among the FIATS-AS scores measured at baseline and 2
      and 8 months after receiving the seating system (F2,134=.22, P=.81). However, the
      FIATS-AS detected a significant interaction between age cohort and interview time
      (F4,134=4.5, P<.001, partial eta(2)=.16). Post hoc testing confirmed that 8
      months after receiving the seating system was associated with a large improvement
      in child and family functioning for children <4 years, maintenance of functioning
      for children between 4 and 12 years, and a moderate decline in functioning for
      youth between 13 and 17 years. CONCLUSIONS: Adaptive seating interventions for
      wheeled mobility devices are associated with functional changes in the lives of
      children and their families that interact inversely with age. Future controlled
      longitudinal studies could provide further empirical evidence of functional
      changes in the lives of children and their families after the introduction and
      long-term use of specific adaptive seating interventions.

PMID- 24035769
TI  - Transcranial direct current stimulation effects in disorders of consciousness.
AB  - OBJECTIVE: To assess the efficacy of transcranial direct current stimulation
      (tDCS) on improving consciousness in patients with persistent unresponsive
      wakefulness syndrome (UWS) (previously termed persistent vegetative state [PVS])
      or in a minimally conscious state (MCS). DESIGN: Prospective, case series trial
      with follow-up at 12 months. SETTING: General and research hospital.
      PARTICIPANTS: Inpatients in a PVS/UWS or MCS (N=10; 7 men, 3 women; age range, 19
      62y; etiology: traumatic brain injury, n=5; anoxia, n=4; postoperative infarct,
      n=1; duration of PVS/UWS or MCS range, 6mo-10y). No participant withdrew because
      of adverse effects. INTERVENTION: All patients received sham tDCS for 20 minutes
      per day, 5 days per week, for 1 week, and real tDCS for 20 minutes per day, 5
      days per week, for 2 weeks. An anodal electrode was placed over the left primary
      sensorimotor cortex or the left dorsolateral prefrontal cortex, with cathodal
      stimulation over the right eyebrow. One patient in an MCS received a second round
      of 10 tDCS sessions 3 months after initial participation. MAIN OUTCOME MEASURE:
      JFK Coma Recovery Scale-Revised. RESULTS: All patients in an MCS showed clinical
      improvement immediately after treatment. The patient who received a second round
      of tDCS 3 months after initial participation showed further improvement and
      emergence into consciousness after stimulation, with no change between
      treatments. One patient who was in an MCS for <1 year before treatment
      (postoperative infarct) showed further improvement and emergence into
      consciousness at 12-month follow-up. No patient showed improvement before
      stimulation. No patient in a PVS/UWS showed immediate improvement after
      stimulation, but 1 patient who was in a PVS/UWS for 6 years before treatment
      showed improvement and change of status to an MCS at 12-month follow-up.
      CONCLUSIONS: tDCS seems promising for the rehabilitation of patients with severe
      disorders of consciousness. Severity and duration of pathology may be related to
      the degree of tDCS' beneficial effects.

PMID- 24035770
TI  - Short versus long course of antibiotics for catheter-associated urinary tract
      infections in patients with spinal cord injury: a randomized controlled
      noninferiority trial.
AB  - OBJECTIVE: To assess the applicability of a short-course regimen of antibiotics
      for managing catheter-associated urinary tract infection (CA-UTI) in patients
      with spinal cord injury (SCI). DESIGN: Randomized, controlled, noninferiority
      trial. SETTING: Medical center. PARTICIPANTS: Patients with SCI who had CA-UTI
      (N=61). INTERVENTIONS: Patients were randomized to receive either a 5-day regimen
      of antibiotics after catheter exchange (experimental group) or a 10-day regimen
      of antibiotics with catheter retention (control group). Noninferiority was
      prespecified with a margin of 10%. MAIN OUTCOME MEASURE: Clinical cure at the end
      of therapy. RESULTS: Of the 61 patients enrolled in this study, 6 patients were
      excluded because of bacteremia or absence of urinary symptoms. All patients
      (100%) achieved clinical cure at the end of therapy. The rates of microbiologic
      response were 82.1% in the experimental group and 88.9% in the control group
      (upper boundary 95% confidence interval (CI) for difference, 26%). The rates of
      resolution of pyuria were 89.3% in the experimental group and 88.9% in the
      control group (upper boundary 95% CI for difference, 16%). Patients in the
      experimental group had higher rates of CA-UTI recurrence than the control group.
      The rates of new CA-UTI, diarrhea, and Clostridium difficile colitis were similar
      in the 2 treatment arms. CONCLUSIONS: The primary endpoint of the study was met,
      indicating that the 5-day regimen with catheter exchange was noninferior to the
      10-day regimen with catheter retention on the basis of clinical cure. Criteria
      for noninferiority on the basis of microbiologic response and resolution of
      pyuria were not met.

PMID- 24035771
TI  - Appropriateness of radiology procedures performed in children with
      gastrointestinal symptoms and conditions.
AB  - BACKGROUND & AIMS: Exposure to ionizing radiation from diagnostic imaging
      procedures (DIPs) has been associated with an increased risk of cancer in
      children. In particular, gastrointestinal imaging has been identified as a
      significant factor that contributes to exposure of children to radiation during
      diagnostic procedures. We performed a longitudinal assessment of gastrointestinal
      associated DIPs to identify practices that might be targeted to reduce exposure
      of pediatric patients to radiation. METHODS: DIP insurance claims from 2001
      through 2009 were obtained from an Independent Physicians Association in a large
      US metropolitan area. We retrieved and analyzed Current Procedural Terminology
      codes, associated International Classification of Diseases, 9th Revision, codes
      specific for gastrointestinal symptoms and conditions, and patient demographics
      associated with DIPs from insurance claims data. RESULTS: Overall, 11,473 DIPs
      were performed on 6550 children with gastrointestinal symptoms; 1 in 30 patients
      received a DIP for a gastrointestinal complaint. Over the study period, the
      proportion of higher-radiation DIPs (computed tomography, fluoroscopy, and
      angiography) increased. Higher-radiation DIPs for gastrointestinal symptoms were
      performed more frequently in older children and in boys in the emergency
      department and in inpatient settings for diagnoses of abdominal pain,
      appendicitis, and noninfectious gastroenteritis. CONCLUSIONS: Higher-radiation
      diagnostic imaging accounts for an increasing proportion of imaging procedures
      among children with gastrointestinal symptoms, even though these often are not
      recommended for evaluation of gastrointestinal disorders. Clinicians should be
      aware of these findings when ordering DIPs for gastrointestinal complaints, and
      clinical practice guidelines should be created to reduce diagnostic imaging
      related radiation exposure in children.

PMID- 24035772
TI  - Reply: To PMID 23333661.

PMID- 24035773
TI  - Prevalence of eosinophilic esophagitis in the United States.
AB  - BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) has become a major cause of
      upper gastrointestinal morbidity in children and adults. However, there are few
      data on the nationwide prevalence of EoE. We aimed to estimate the prevalence of
      EoE in the United States. METHODS: We collected health insurance claims from a
      large database that represented the U.S. commercially insured population. We
      analyzed data from 2008 to 2011, identifying cases of EoE by using a previously
      validated definition, and calculated a period prevalence by using data from 2009
      to 2011. EoE was defined as any instance of the International Classification of
      Diseases, 9th revision code 530.13. We calculated the prevalence of the code in
      the database and standardized the estimate to the U.S. population. RESULTS: Of
      35,575,388 individuals in this database, 16,405 had at least 1 code for EoE. The
      mean age was 33.5 years, 65% were male, 55.8% had dysphagia, and 52.8% had a
      diagnostic code for at least 1 allergic condition. Among 11,569,217 individuals
      with continuous insurance coverage between mid-2009 and mid-2011, 6513 had at
      least 1 code for EoE. When standardized to the U.S. population, the estimated
      period prevalence of EoE was 56.7/100,000 persons, translating to approximately
      152,152 cases in the U.S. Prevalence peaked in men 35-39 years old, with a rate
      of 114.6/100,000 persons. CONCLUSIONS: Despite its relatively recent description,
      EoE is frequently diagnosed in the United States, with an estimated prevalence of
      56.7/100,000 persons. This estimate depends on the accuracy of the International
      Classification of Diseases, 9th revision code, but it could be an underestimate,
      because knowledge of the code and recognition of EoE are increasing.

PMID- 24035774
TI  - Relationship between level of hepatitis B virus DNA and liver disease: a
      population-based study of hepatitis B e antigen-negative persons with hepatitis
      B.
AB  - BACKGROUND & AIMS: There is little information on the proportion of persons with
      chronic hepatitis B virus (HBV) infection with active hepatitis. We aimed to
      determine the proportion of persons with hepatitis B e antigen-negative chronic
      HBV infection who develop immune-active HBV infection over time and the
      relationship between demographic and viral factors on severity of disease on
      liver biopsy. METHODS: We performed a longitudinal population-based cohort study
      of 754 Alaska Native patients with chronic HBV infection. Levels of alanine
      aminotransferase (ALT) were measured every 6 months, and levels of HBV DNA were
      measured at study entry and whenever ALT levels exceeded the upper limit of
      normal (ULN). Immune-active chronic HBV infection was defined as levels of ALT >=
      30 U/L in men and >20 U/L in women and levels of HBV DNA >2000 IU/mL at 1 or more
      time points from 2001-2008. Liver biopsies were scored by using the modified
      histology activity index score of Knodell and the Ishak fibrosis score. RESULTS:
      Of the study participants, 186 (25%) met the criteria for immune-active HBV, 56%
      of these initially and 44% later during follow up. Of the 38 patients with liver
      biopsy results, only 1 of 16 with ALT levels consistently below twice the ULN and
      1 of 19 with HBV DNA between 2000 and 20,000 IU/mL, vs 12 of 22 (55%) with ALT >
      twice ULN (P = .002) and 11 of 18 (61%) with 1 or more measurements of HBV DNA
      >20,000 IU/mL (P < .001), had moderate or severe hepatitis or fibrosis.
      CONCLUSIONS: In a cohort of Alaska Natives with chronic HBV infection, 25% met
      criteria for immune-active HBV. There is a low probability of advanced fibrosis
      if levels of HBV DNA never exceed 20,000 IU/mL.

PMID- 24035775
TI  - Obstructive sleep apnea is a risk factor for Barrett's esophagus.
AB  - BACKGROUND & AIMS: Common risk factors for obstructive sleep apnea (OSA) and
      Barrett's esophagus (BE) include obesity and gastroesophageal reflux disease
      (GERD). The aims of this study were to assess the association between OSA and BE
      and to determine whether the association is independent of GERD and body mass
      index (BMI). METHODS: Patients who had undergone a diagnostic polysomnogram and
      esophagogastroduodenoscopy were identified by using Mayo Clinic (Rochester,
      Minnesota) databases from January 2000-November 2011. They were randomly matched
      for age, sex, and BMI at time of polysomnogram into the following groups: BE but
      no OSA (n = 36), OSA but no BE (n = 78), both (n = 74), or neither (n = 74).
      Clinical and demographic variables were abstracted from medical records. The
      association between OSA and BE was assessed by using a multiple variable logistic
      model that incorporated age, sex, BMI, clinical diagnosis of GERD, and smoking
      history. RESULTS: Subjects with OSA had an 80% increased risk for BE compared
      with subjects without OSA (odds ratio, 1.8; 95% confidence interval, 1.1-3.2; P =
      .03). These findings were independent of age, sex, BMI, GERD, and smoking
      history. Increasing severity of OSA, measured by using the apnea-hypopnea index,
      was associated with an increased risk of BE (odds ratio, 1.2 per 10-unit increase
      in apnea-hypopnea index; 95% confidence interval, 1.0-1.3; P = .03). CONCLUSIONS:
      In this case-control study, OSA was associated with an increased risk of BE,
      potentially through BMI and GERD independent mechanisms. Patients with OSA may
      benefit from evaluation for BE.

PMID- 24035777
TI  - Health care reform 3.0: the road gets bumpy.

PMID- 24035776
TI  - Food allergy testing in eosinophilic esophagitis: what the gastroenterologist
      needs to know.
AB  - Eosinophilic esophagitis (EoE) is a clinicopathologic disease of increasing
      prevalence in children and adults. The triggering antigen in EoE is often a food
      that initiates a cascade of Th2-associated interleukins such as interleukin-5 and
      interleukin-13 and chemokines such as eotaxin-3 as well as esophageal
      eosinophilia and mastocytosis. Amino acid-based formulas have high efficacy rates
      in EoE and constitute the first evidence for food-triggered esophageal
      eosinophilia. Animal models have demonstrated the sufficiency of food antigens in
      triggering both the inflammatory and remodeling complications of EoE. Food
      elimination diets that are followed by single food introduction with repeat
      biopsy have proven the efficacy of empiric and allergy testing based elimination
      diets in children and adults. Although the ideal allergy test for identifying
      food antigens in EoE remains to be elucidated, the utility of food skin prick
      combined with atopy patch testing has been shown in large pediatric cohorts. By
      comparison, smaller, non-U.S. adult cohorts have not had similar results.
      Currently, a positive test on food allergy evaluation suggests a food trigger for
      EoE but does not substitute for biopsy-based tissue evaluation after food removal
      and reintroduction. The higher rates of food anaphylaxis in children with EoE,
      potential loss of tolerance to immunoglobulin E-positive foods that can occur
      with food avoidance, and the high rates of other atopic diatheses in EoE subjects
      all support the evaluation of EoE subject by an allergist, consideration for
      allergy testing, and an integrated approach by allergists, gastroenterologists,
      and pathologists in EoE management. 

PMID- 24035778
TI  - Dynamics of human telomerase RNA structure revealed by antisense oligonucleotide
      technique.
AB  - Telomeres are the nucleoprotein complexes that cap the linear chromosome ends.
      Telomerase is a ribonucleoprotein that maintains telomere length in stem,
      embryonic and cancer cells. Somatic cells don't contain active telomerase and
      telomere function as mitotic clock and telomere length determines the number of
      cell divisions. Telomerase RNA (TER) contains the template for telomere synthesis
      and serves as a structural scaffold for holoenzyme assembly. We compared
      different oligonucleotide based methods for telomerase RNA inhibition, such as
      antisense oligonucleotides, knockdown by transient siRNA transfection and
      silencing by miRNA derived from short expressed RNA hairpin in HEK293 cells. All
      of these methods were applied to different TER regions. Our results revealed that
      CR2/CR3 domain of TER is accessible in vitro and in vivo and could serve as an
      optimal site for oligonucleotide-based telomerase silencing.

PMID- 24035779
TI  - Biochemical, functional, structural and phylogenetic studies on Intercro, a new
      isoform phospholipase A2 from Crotalus durissus terrificus snake venom.
AB  - Crotoxin is a neurotoxin from Crotalus durissus terrificus venom that shows
      immunomodulatory, anti-inflammatory, antimicrobial, antitumor and analgesic
      activities. Structurally, this toxin is a heterodimeric complex composed by a
      toxic basic PLA2 (Crotoxin B or CB) non-covalently linked to an atoxic non
      enzymatic and acidic component (Crotapotin, Crotoxin A or CA). Several CA and CB
      isoforms have been isolated and characterized, showing that the crotoxin venom
      fraction is, in fact, a mixture of different molecules derived from the
      combination of distinct subunit isoforms. Intercro (IC) is a protein from the
      same snake venom which presents high similarity in primary structure to CB,
      indicating that it could be an another isoform of this toxin. In this work, we
      compare IC to the crotoxin complex (CA/CB) and/or CB in order to understand its
      functional aspects. The experiments with IC revealed that it is a new toxin with
      different biological activities from CB, keeping its catalytic activity but
      presenting low myotoxicity and absence of neurotoxic activity. The results also
      indicated that IC is structurally similar to CB isoforms, but probably it is not
      able to form a neurotoxic active complex with crotoxin A as observed for CB.
      Moreover, structural and phylogenetic data suggest that IC is a new toxin with
      possible toxic effects not related to the typical CB neurotoxin. 

PMID- 24035780
TI  - Level of vascular endothelial growth factor predicts both relapse and nonrelapse
      mortality after allogeneic hematopoietic stem cell transplantation.
AB  - Although the prognostic significance of vascular endothelial growth factor (VEGF)
      has been researched extensively in patients with hematologic malignancies
      undergoing chemotherapy, its role in allogeneic hematopoietic stem cell
      transplantation (HSCT) requires further investigation. The present study
      evaluated the associations between VEGF level and relapse rate and early
      complications after HSCT. VEGF levels were analyzed in 91 consecutive patients
      before the start of conditioning, on day 0, on the day of engraftment, and on the
      day of diagnosis of veno-occlusive disease (VOD). Compared with a normal level,
      an elevated high VEGF-A level before conditioning was associated with an
      increased 2-year relapse rate (55% versus 24%, P = .003; hazard ratio [HR], 3.25;
      95% confidence interval [CI], 1.49 to 7.08) and decreased event-free survival
      (20% versus 44%; P = .022; HR, 2.03; 95% CI, 1.11 to 3.72). No association was
      found between VEGF level and the incidence of acute GVHD (P > .05). In patients
      with VOD, VEGF-A level was elevated on day 0 and on the day of VOD diagnosis (P <
      .05). A low VEGF-A level on day 0 was associated with reduced nonrelapse
      mortality (14% versus 35%; P = .048; HR, 0.32; 95% CI, 0.10 to 0.99). Our results
      indicate that a high VEGF-A level before HSCT increases the risk of relapse, and
      a high level after conditioning is associated with increased risks of early
      complications and nonrelapse mortality.

PMID- 24035781
TI  - Immune recovery in pediatric transplantation: can T cell-depleted peripheral
      blood stem cell transplantation beat cord blood transplantation?

PMID- 24035782
TI  - An intermediate alemtuzumab schedule reduces the incidence of mixed chimerism
      following reduced-intensity conditioning hematopoietic cell transplantation for
      hemophagocytic lymphohistiocytosis.
AB  - Reduced-intensity conditioning (RIC) improves the outcomes of hematopoietic cell
      transplantation (HCT) in patients with hemophagocytic lymphohistiocytosis (HLH).
      Proximal (ie, close to graft infusion) dosing of alemtuzumab is associated with a
      high incidence of mixed chimerism, whereas distal (ie, distant from graft
      infusion) dosing is associated with less mixed chimerism but more acute graft
      versus-host disease (GVHD). The alemtuzumab dose per kilogram of body weight also
      influences these outcomes. We hypothesized that an intermediate alemtuzumab
      dosing schedule would reduce mixed chimerism and maintain a low incidence of
      acute GVHD. In this study, 24 consecutive HCTs were performed in patients with
      HLH or a related disorder using a novel intermediate alemtuzumab schedule of 1
      mg/kg starting on day -14. The cumulative incidences (CIs) of mixed chimerism,
      upfront acute GVHD grades II-IV, and receipt of additional hematopoietic cell
      products after HCT were compared in patients treated with a distal alemtuzumab
      schedule (n = 15) and those treated with a proximal alemtuzumab schedule (n =
      33). All patients received fludarabine and melphalan. The CI of mixed chimerism
      was 31% in the intermediate group, 72% in the proximal group (P < .01), and 75%
      in the distal group patients who received >=2 mg/kg alemtuzumab (P = .03). The CI
      of acute GVHD grades II-IV before the development of mixed chimerism was 4% in
      the intermediate group, 0% in the proximal group, and 13% in the distal group (P
      = .04, proximal versus distal). The 1-year CI of administration of additional
      hematopoietic cell products for mixed chimerism (donor lymphocyte infusion +/-
      hematopoietic stem cell boost +/- repeat HCT) was 14% in the intermediate group,
      53% in the proximal group (P = .01), and 38% in the distal >=2 mg/kg alemtuzumab
      group (P = .02). Our findings indicate that intermediate RIC reduces the
      incidence of mixed chimerism, is associated with a low incidence of upfront acute
      GVHD, and decreases the need for additional hematopoietic cell products after
      HCT. 

PMID- 24035783
TI  - Proceedings from the National Cancer Institute's Second International Workshop on
      the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell
      Transplantation: introduction.
AB  - Despite advances in hematopoietic stem cell transplantation (HSCT) for the
      treatment of hematologic malignancies, relapse remains the leading cause of death
      after transplant. Biologic and clinical investigations are needed to combat this
      primary cause of death after transplantation. The National Cancer Institute held
      international workshops in 2009 and 2012 to help address this problem. Three
      major initiatives for coordinated research were proposed: 1) To establish
      multicenter networks for basic, translational, epidemiologic and clinical
      research; 2) To establish a network of biorepositories for the collection of
      samples before and after HSCT to aid in laboratory and clinical studies; and 3)
      To refine, implement and study proposed definitions for disease-specific response
      and relapse and for monitoring of minimal residual disease. The workshop in 2012
      also featured nine presentations, summaries of which follow in three manuscripts.

PMID- 24035784
TI  - Implications of the O-GlcNAc modification in the regulation of nuclear apoptosis
      in T cells.
AB  - BACKGROUND: O-linked beta-N-acetylglucosamine (O-GlcNAc) is a nutrient-/stress
      sensitive post-translational modification that affects nucleocytoplasmic
      proteins. The enzyme O-N-acetylglucosamine transferase (OGT) catalyzes the
      addition of O-GlcNAc, whereas O-N-acetylglucosaminidase (OGA) removes it. O
      GlcNAcylation plays a role in fundamental regulatory mechanisms through the
      modification of proteins involved in cell division, metabolism, transcription,
      cell signaling and apoptosis. The effects of O-GlcNAcylation on apoptosis appear
      to be cell-dependent, as elevated levels played a protective role in primary
      neonatal rat ventricular myocytes but had a cytotoxic effect in rat pancreatic
      beta-cells. The aim of the current study was to determine the implications of the
      O-GlcNAc modification on T cell apoptosis. METHODS: Human T lymphoblastic HPB-ALL
      cells were treated with the OGA inhibitor O-(2-acetamido-2-deoxy-d
      glucopyranosylidene) amino-N-phenylcarbamate (PUGNAc), or with glucosamine
      (GlcN), to increase O-GlcNAcylation. Apoptosis was induced in the presence of
      tributyltin (TBT). DNA fragmentation was observed by cell cycle analysis and
      corresponded to the sub G0/G1 population. O-GlcNAcylated proteins were detected
      by immunoblot using a specific antibody (ctd110.6) and were precipitated using
      succinylated wheat germ agglutinin (sWGA). RESULTS: HPB-ALL cells treated with
      PUGNAc displayed a significant reduction in DNA fragmentation after TBT-induced
      apoptosis. DFF45, the protein that inhibits the endonuclease DFF40, was
      identified to be O-GlcNAc modified. O-GlcNAcylated DFF45 appeared to be more
      resistant to caspase cleavage during apoptosis. Our results suggest that a
      decrease in the O-GlcNAc modification on DFF45 occurs before its cleavage by
      caspase. GENERAL SIGNIFICANCE: Our results indicate that the O-GlcNAcylation of
      DFF45 may represent a mechanism to control the accidental activation of DFF.

PMID- 24035785
TI  - Resveratrol enhances TNF-alpha production in human monocytes upon bacterial
      stimulation.
AB  - BACKGROUND: Resveratrol is a key component of red wine that has been reported to
      have anti-carcinogenic and anti-aging properties. Additional studies conducted in
      vitro and in animal models suggested anti-inflammatory properties. However, data
      from primary human immune cells and in vivo studies are limited. METHODS: A pilot
      study was performed including 10 healthy volunteers. Plasma cytokine levels were
      measured over 48h after oral application of 5g resveratrol. To verify the in vivo
      findings, cytokine release and gene expression in human peripheral blood
      mononuclear cells (PBMC) and/or monocytes was assessed after treatment with
      resveratrol or its metabolites and stimulation with several toll-like receptor
      (TLR)-agonists. Additionally, the impact on intracellular signaling pathways was
      analyzed using a reporter cell line and Western blotting. RESULTS: Resveratrol
      treated individuals showed a significant increase in tumor necrosis factor-alpha
      (TNF-alpha) levels 24h after treatment compared to baseline. Studies using human
      PBMC or isolated monocytes confirmed potentiation of TNF-alpha production with
      different TLR agonists, while interleukin (IL)-10 was inhibited. Moreover, we
      observed significantly enhanced nuclear factor 'kappa-light-chain-enhancer' of
      activated B-cells (NF-kappaB) activation using a reporter cell line and found
      increased phosphorylation of p105, which is indicative of alternative NF-kappaB
      pathway activation. GENERAL SIGNIFICANCE: By administering resveratrol to healthy
      humans and utilizing primary immune cells we were able to detect TNF-alpha
      enhancing properties of the agent. In parallel, we found enhanced alternative NF
      kappaB activation. We report on a novel pro-inflammatory property of resveratrol
      which has to be considered in concepts of its biologic activity.

PMID- 24035786
TI  - Pro-oxidative effects of aggregated transthyretin in human Schwannoma cells.
AB  - Neurotoxicity mechanisms of amyloidogenic polypeptides such as transthyretin
      (TTR) are not well understood. Misfolded and aggregated TTRs (agTTR) lead to age
      related diseases such as senile systemic amyloidosis and familial amyloid
      polyneuropathy (FAP). Among other clinical manifestations in TTR amyloidic
      disease, peripheral nerve tissue, including Schwann cell, degeneration has been
      observed. In this study, we examined potential toxic effects of agTTR in human
      Schwannoma cells (sNF94.3 peripheral nerve sheath line). Cells were treated with
      agTTR (2.4MUM pre-aggregation concentration) or, as controls, normal, soluble TTR
      (2.4MUM) or no-TTR treatment, and then analyzed for different pro-oxidant and
      anti-oxidant markers: hydrogen peroxide (H2O2), catalase (CAT), glutathione
      (GSH), and more generalized cellular antioxidant capacity. In the latter case,
      cytosolic fractions were prepared after agTTR (or control) treatments and
      analyzed in oxidation assays. Relative to treatment with normal soluble TTR,
      cells treated with agTTR increase their release of H2O2. Residual CAT activity is
      decreased after agTTR treatment. The Schwannoma cells also exhibit significantly
      lower levels of GSH after agTTR treatment (p<0.05, relative to controls). More
      generally, cytosols from agTTR-treated cells exhibited a lower capacity to
      prevent oxidation relative to those from control cells (TTR-treated, or non-TTR
      treated). These results suggest that agTTR (a) stimulates production of reactive
      oxygen species, (b) leads to lower levels of endogenous antioxidants, and (c)
      decreases overall cellular antioxidant capacity, in Schwannoma cells. 

PMID- 24035787
TI  - Effects of aging and dopamine genotypes on the emergence of explicit memory
      during sequence learning.
AB  - The striatum and medial temporal lobe play important roles in implicit and
      explicit memory, respectively. Furthermore, recent studies have linked striatal
      dopamine modulation to both implicit as well as explicit sequence learning and
      suggested a potential role of the striatum in the emergence of explicit memory
      during sequence learning. With respect to aging, previous findings indicated that
      implicit memory is less impaired than explicit memory in older adults and that
      genetic effects on cognition are magnified by aging. To understand the links
      between these findings, we investigated effects of aging and genotypes relevant
      for striatal dopamine on the implicit and explicit components of sequence
      learning. Reaction time (RT) and error data from 80 younger (20-30 years) and 70
      older adults (60-71 years) during a serial reaction time task showed that age
      differences in learning-related reduction of RTs emerged gradually over the
      course of learning. Verbal recall and measures derived from the process
      dissociation procedure revealed that younger adults acquired more explicit memory
      about the sequence than older adults, potentially causing age differences in RT
      gains in later stages of learning. Of specific interest, polymorphisms of the
      dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32, rs907094) and
      dopamine transporter (DAT, VNTR) genes showed interactive effects on overall RTs
      and verbal recall of the sequence in older but not in younger adults. Together
      our findings show that variations in genotypes relevant for dopamine functions
      are associated more with aging-related impairments in the explicit than the
      implicit component of sequence learning, providing support for theories
      emphasizing the role of dopaminergic modulation in cognitive aging and the
      magnification of genetic effects in human aging. 

PMID- 24035788
TI  - Thalamic and parietal brain morphology predicts auditory category learning.
AB  - Auditory categorization is a vital skill involving the attribution of meaning to
      acoustic events, engaging domain-specific (i.e., auditory) as well as domain
      general (e.g., executive) brain networks. A listener's ability to categorize
      novel acoustic stimuli should therefore depend on both, with the domain-general
      network being particularly relevant for adaptively changing listening strategies
      and directing attention to relevant acoustic cues. Here we assessed adaptive
      listening behavior, using complex acoustic stimuli with an initially salient (but
      later degraded) spectral cue and a secondary, duration cue that remained
      nondegraded. We employed voxel-based morphometry (VBM) to identify cortical and
      subcortical brain structures whose individual neuroanatomy predicted task
      performance and the ability to optimally switch to making use of temporal cues
      after spectral degradation. Behavioral listening strategies were assessed by
      logistic regression and revealed mainly strategy switches in the expected
      direction, with considerable individual differences. Gray-matter probability in
      the left inferior parietal lobule (BA 40) and left precentral gyrus was
      predictive of "optimal" strategy switch, while gray-matter probability in
      thalamic areas, comprising the medial geniculate body, co-varied with overall
      performance. Taken together, our findings suggest that successful auditory
      categorization relies on domain-specific neural circuits in the ascending
      auditory pathway, while adaptive listening behavior depends more on brain
      structure in parietal cortex, enabling the (re)direction of attention to salient
      stimulus properties. 

PMID- 24035789
TI  - Internal mouthpiece designs as a future perspective for enhanced aerosol
      deposition. Comparative results for aerosol chemotherapy and aerosol antibiotics.
AB  - BACKGROUND: In an effort to identify factors producing a finest mist from Jet
      Nebulizers we designed 2 mouthpieces with 4 different internal designs and 1-3
      compartments. MATERIALS AND METHODS: Ten different drugs previous used with their
      "ideal" combination of jet-nebulizer, residual-cup and loading were used. For
      each drug the mass median aerodynamic diameter size had been established along
      with their "ideal" combination. RESULTS: For both mouthpiece, drug was the most
      important factor due the high F-values (Flarge=251.7, p<0.001 and Fsmall=60.1,
      p<0.001) produced. The design affected the droplet size but only for large
      mouthpiece (Flarge=5.99, p=0.001, Fsmall=1.72, p=0.178). Cross designs create the
      smallest droplets (2.271) so differing from the other designs whose mean droplets
      were greater and equal ranging between 2.39 and 2.447. The number of compartments
      in the two devices regarding the 10 drugs was found not statistically significant
      (p-values 0.768 and 0.532 respectively). Interaction effects between drugs and
      design were statistically significant for both devices (Flarge=8.87, p<0.001,
      Fsmall=5.33, p<0.001). CONCLUSION: Based on our experiment we conclude that
      further improvement of the drugs intended for aerosol production is needed. In
      addition, the mouthpiece design and size play an important role in further
      enhancing the fine mist production and therefore further experimentation is
      needed.

PMID- 24035791
TI  - Disentangling the complexity of infectious diseases: Time is ripe to improve the
      first-line statistical toolbox for epidemiologists.
AB  - Because many biological processes related to the dynamics of infectious diseases
      are caused by complex interactions between the environment, the host(s) and the
      agent(s), the necessity to address the methodological implications of this
      inherent complexity has recently emerged in epidemiology. Most epidemiologists
      now acknowledge that most human infectious diseases are likely to have complex
      dynamics. However, this knowledge still percolates with difficulty in their
      statistical "modus operandi". Indeed, for the study of complex systems, the
      traditional first-line statistical toolbox of epidemiologists (mainly built
      around the Generalized Linear Model family), despite its undeniable practicality
      and robustness, has structural limitations deprecating its usefulness. Three
      major sources of complexity neglected or not taken into account by this first
      line statistical toolbox and having deep statistical implications are the multi
      level organization of data, the non-linear relationships between variables and
      the complex interactions between variables. Three promising candidates to
      incorporate along with traditional tools for a new first-line statistical toolbox
      more suitable to apprehend these sources of complexity are the generalized linear
      mixed models, the generalized additive models, and the structural equation
      models. The aforementioned methodologies have the advantage to be generalizations
      of GLM models and are relatively easy to implement. Their assimilation and
      implementation would thus be greatly facilitated for epidemiologists. More
      globally, this text underlines that an improved use of other methods as such
      described here compared to traditional ones has to be performed to better
      understand the complexity challenging epidemiologists every day. This is
      particularly true in the field of infectious diseases for which major public
      health challenges will have to be addressed in the coming decades. 

PMID- 24035790
TI  - Global distribution and diversity of ovine-associated Staphylococcus aureus.
AB  - Staphylococcus aureus is an important pathogen of many species, including sheep,
      and impacts on both human and animal health, animal welfare, and farm
      productivity. Here we present the widest global diversity study of ovine
      associated S. aureus to date. We analysed 97 S. aureus isolates from sheep and
      sheep products from the UK, Turkey, France, Norway, Australia, Canada and the USA
      using multilocus sequence typing (MLST) and spa typing. These were compared with
      196 sheep isolates from Europe (n=153), Africa (n=28), South America (n=14) and
      Australia (n=1); 172 bovine, 68 caprine and 433 human S. aureus profiles. Overall
      there were 59 STs and 87 spa types in the 293 ovine isolates; in the 97 new ovine
      isolates there were 22 STs and 37 spa types, including three novel MLST alleles,
      four novel STs and eight novel spa types. Three main CCs (CC133, CC522 and CC700)
      were detected in sheep and these contained 61% of all isolates. Four spa types
      (t002, t1534, t2678 and t3576) contained 31% of all isolates and were associated
      with CC5, CC522, CC133 and CC522 respectively. spa types were consistent with
      MLST CCs, only one spa type (t1403) was present in multiple CCs. The three main
      ovine CCs have different but overlapping patterns of geographical dissemination
      that appear to match the location and timing of sheep domestication and selection
      for meat and wool production. CC133, CC522 and CC700 remained ovine-associated
      following the inclusion of additional host species. Ovine isolates clustered
      separately from human and bovine isolates and those from sheep cheeses, but
      closely with caprine isolates. As with cattle isolates, patterns of clonal
      diversification of sheep isolates differ from humans, indicative of their
      relatively recent host-jump. 

PMID- 24035792
TI  - Replication study in Chinese Han population and meta-analysis supports
      association between the MBL2 gene polymorphism and HIV-1 infection.
AB  - Mannose-binding lectin (MBL) plays an important role in immunity to HIV-1
      infection. The exon1 coding polymorphisms of the MBL2 gene have been implicated
      in the susceptibility to HIV-1 infection, but the results were controversial. In
      the present study, a case-control study in a Chinese population was conducted to
      replicate the association, and then a meta-analysis combing our new data and
      published data was performed to clarify these findings. In total, 15 studies
      consisting 2219 HIV-1 patients and 2744 controls were included. Odds ratios (ORs)
      with 95% confidence intervals (95% CIs) were assessed in the main analyses. By
      dividing the controls into two groups, healthy controls and HIV-1 exposed but
      seronegative (HESN) controls, we explored different genetic models and allelic
      model to detect the association. By using the healthy controls, we found that the
      MBL2 exon 1 polymorphisms were associated with hosts' susceptibility to HIV-1
      infection in dominant model (p=0.01, 95% CI 1.05-1.43), recessive model
      (p<0.0001, 95% CI 1.35-2.28), allelic model (p<0.0001, 95% CI 1.12-1.37) and O/O
      vs. A/A model (p<0.00001, 95% CI 1.40-2.38). In the subgroup analysis by
      ethnicity, significant elevated risks were found in Caucasians (recessive model:
      p<0.0001, 95% CI 1.36-2.51), but not in Asians (recessive model: p=0.10, 95% CI
      0.91-2.77). Collectively, our findings from our case-control replication study
      and meta-analysis suggested that the MBL2 gene exon 1 coding variants were
      associated with hosts' susceptibility to HIV-1 infection, especially in
      Caucasians, but not in Asians. 

PMID- 24035793
TI  - Reconstructing the origin and transmission dynamics of the 1967-68 foot-and-mouth
      disease epidemic in the United Kingdom.
AB  - A large epidemic of foot-and-mouth disease (FMD) occurred in the United Kingdom
      (UK) over a seven month period in Northwest England from late 1967 to the summer
      of 1968. This was preceded by a number of smaller FMD outbreaks in the country,
      two in 1967, in Hampshire and Warwickshire and one in Northumberland during 1966.
      The causative agent of all four events was identified as FMD virus (FMDV)
      serotype O and the source of the large epidemic was attributed to infected bone
      marrow in lamb products imported from Argentina. However, the diagnostic tools
      available at the time were unable to entirely rule out connections with the
      earlier UK FMD outbreaks, as well as other potential sources from Europe. The aim
      of this study was to apply molecular sequencing to investigate the likely source
      of this epidemic using VP1 region and full genome (FG) sequences determined
      directly from clinical epithelium samples (n=13) or cell culture isolates (n=6),
      from this and contemporary outbreaks in the UK, Europe and South America.
      Analysis of the VP1 sequences provided evidence for at least three separate
      incursions of FMDV into the UK including one independent introduction that was
      responsible for the main 1967/68 epidemic. Analysis of FG sequences from the main
      1967/68 outbreak (n=10) revealed nucleotide substitutions at 94 genomic sites
      providing evidence for the linear accumulation of nucleotide substitutions
      (rate=2.42 * 10(-)(5)nt substitutions/site/day). However, there were five samples
      where this linear relationship was absent, indicating evolutional dormancy of the
      virus, presumably outside a host. These results help define the evolutionary
      dynamics of FMDV during an epidemic and contribute to the knowledge and
      understanding from which to base future outbreak control strategies.

PMID- 24035794
TI  - Arthritis and onycophagia: a confounding factor.

PMID- 24035795
TI  - Macrophage activation syndrome as the initial manifestation of severe juvenile
      onset systemic lupus erythematosus. Favorable response to cyclophosphamide.
AB  - The macrophage activation syndrome is a rare but potentially fatal complication
      of patients with autoimmune rheumatic diseases. This is a clinicopathological
      entity characterized by activation of histiocytes with prominent hemophagocytosis
      in the bone marrow and other reticuloendothelial systems. In patients with lupus
      it may mimic an exacerbation of the disease or infection. We report the case of a
      7-year-old girl in whom the diagnosis of lupus erythematosus and macrophage
      activation syndrome was simultaneously made with response to the use of
      cyclophosphamide. 

PMID- 24035796
TI  - Frequency of gout according to the perception of physicians in Mexico.

PMID- 24035797
TI  - Beneficiation of limestone plant rejects for value addition.
AB  - Investigations were carried out on lime stone rejects (-1mm) generated at a lime
      stone washing plant in southern India. These rejects contain 12.09% CaO, 2.95%
      MgO, 10.73% Al2O3, 4.99% Fe2O3, 43.05% SiO2 and 24.92% LOI. Mineralogical studies
      including SEM-EDAX, XRD, FTIR and TGA were conducted to confirm relative
      distribution of minerals in the flotation feed and products. These studies
      revealed that feed sample consists of quartz and calcite as the major minerals
      with minor amounts of montmorillonite and dolomite whereas flotation concentrate
      dominantly consists of calcite, and tailings mostly of quartz and
      montmorillonite. A commercial grade sodium silicate, oleic acid and MIBC were
      used as depressant, collector and frother respectively in flotation studies. The
      effects of different operating parameters were evaluated for both conventional
      and column flotation. Two stage conventional cell flotation results indicate that
      a cleaner concentrate of 42.50% lime (CaO) content could be obtained at a yield
      of 15.65%. The lime (CaO) content of the concentrate was further enhanced up to
      44.23% at 20.73% yield using single stage column flotation. The column flotation
      is more efficient in comparison to the conventional cell for treating this
      sample. A process flowsheet was developed to treat these rejects based on the
      studies carried out. This process can minimize the waste generation and the
      concentrate generated during this process can be directly utilized in the Indian
      cement industries. 

PMID- 24035798
TI  - Perchlorate contamination from the detonation of insensitive high-explosive
      rounds.
AB  - The insensitive high-explosive PAX-21 was the first of its kind fielded in an
      artillery munition by the United States military. This formulation contains three
      main components: RDX, dinitroanisole, and ammonium perchlorate (AP). In March
      2012, detonation tests were conducted on PAX-21 60mm mortar rounds to determine
      the energetic residues resulting from high-order and blow-in-place (BIP)
      detonations. Post-detonation residues were sampled and analyzed for the three
      main PAX-21 components. Concentrations of RDX and dinitroanisole in the samples
      were quite low, less than 0.1% of the munitions' original organic explosive
      filler mass, indicating high order or near high order detonations. However,
      disproportionately high concentrations of AP occurred in all residues. The
      residues averaged 15% of the original AP following high-order detonations and 38%
      of the original AP mass following the BIP operations. There was no correlation
      between AP residues and the RDX and dinitroanisole. Perchlorate readily leached
      from the detonation residues, with over 99% contained in the aqueous portion of
      the samples. Use of these rounds will result in billions of liters of water
      contaminated above drinking water perchlorate limits. As a result of this
      research, PAX-21 mortar rounds are currently restricted from use on US training
      ranges. 

PMID- 24035799
TI  - Simultaneous bioreduction of nitrate and chromate using sulfur-based mixotrophic
      denitrification process.
AB  - This study aims at evaluating simultaneous chromate and nitrate reduction using
      sulfur-based mixotrophic denitrification process in a column reactor packed with
      elemental sulfur and activated carbon. The reactor was supplemented with methanol
      at C/N ratio of 1.33 or 2. Almost complete denitrification was achieved at
      influent NO3(-)-N and Cr(VI) concentrations of 75 mg/L and 10mg/L, respectively,
      and 3.7h HRT. Maximum denitrification rate was 0.5 g NO3(-)-N/(L.d) when the
      bioreactor was fed with 75 mg/L NO3(-)-N, 150 mg/L methanol and 10mg/L Cr(VI).
      The share of autotrophic denitrification was between 12% and 50% depending on
      HRT, C/N ratio and Cr(VI) concentration. Effluent total chromium was below 50
      MUg/L provided that influent Cr(VI) concentration was equal or below 5mg/L. DGGE
      results showed stable microbial community throughout the operation and the
      presence of sulfur oxidizing denitrifying bacteria (Thiobacillus denitrificans)
      and Cr(VI) reducing bacteria (Exiguobacterium spp.) in the column bed.

PMID- 24035800
TI  - [Charles Bonnet syndrome secondary to panretinal photocoagulation].

PMID- 24035801
TI  - Developmental changes in expression and biophysics of ion channels in the canine
      ventricle.
AB  - BACKGROUND: Developmental changes in the electrical characteristics of the
      ventricular myocardium are not well defined. This study examines the contribution
      of inwardly rectifying K(+) current (IK1), transient outward K(+) current (Ito),
      delayed rectifier K(+) currents (IKr and IKs) and sodium channel current (INa) to
      repolarization in the canine neonate myocardium. METHODS: Single myocytes
      isolated from the left ventricle of 2-3week old canine neonate hearts were
      studied using patch-clamp techniques. RESULTS: Neonate cells were ~6-fold smaller
      than those of adults (28.8+/-8.8 vs. 176+/-6.7pF). IK1 was larger in neonate
      myocytes and displayed a substantial inward component and an outward component
      with negative slope conductance, peaking at -60mV (4.13 pA/pF). IKr tail currents
      (at -40mV), were small (<20pA). IKs could not be detected, even after exposure to
      isoproterenol (100nM). Ito was also absent in the neonate, consistent with the
      absence of a phase 1 in the action potential. Peak INa, late INa and ICa were
      smaller in the neonate compared with adults. KCND3, KCNIP2 and KCNQ1 mRNA
      expression was half, while KCNH2 was equal and KCNJ2 was greater in the neonate
      when compared with adults. CONCLUSIONS: Two major repolarizing K(+) currents (IKs
      and Ito) present in adult ventricular cells are absent in the 2week old neonate.
      Peak and late INa are significantly smaller in the neonate. Our results suggest
      that the absence of these two currents in the neonate heart may increase the
      susceptibility to arrhythmias under certain long QT conditions.

PMID- 24035802
TI  - The ethics of placebo-controlled trials: methodological justifications.
AB  - The use of placebo controls in clinical trials remains controversial. Ethical
      analysis and international ethical guidance permit the use of placebo controls in
      randomized trials when scientifically indicated in four cases: (1) when there is
      no proven effective treatment for the condition under study; (2) when withholding
      treatment poses negligible risks to participants; (3) when there are compelling
      methodological reasons for using placebo, and withholding treatment does not pose
      a risk of serious harm to participants; and, more controversially, (4) when there
      are compelling methodological reasons for using placebo, and the research is
      intended to develop interventions that can be implemented in the population from
      which trial participants are drawn, and the trial does not require participants
      to forgo treatment they would otherwise receive. The concept of methodological
      reasons is essential to assessing the ethics of placebo controls in these
      controversial last two cases. This article sets out key considerations relevant
      to considering whether methodological reasons for a placebo control are
      compelling. 

PMID- 24035803
TI  - Multiphase renal CT in the evaluation of renal masses: is the nephrographic phase
      necessary?
AB  - The aim of this study is to investigate the feasibility of eliminating the
      nephrographic phase from the four-phase renal computed tomography (CT) imaging to
      a three-phase protocol without affecting its diagnostic value. Thirty patients
      undergoing four-phase renal CT scans for assessment of renal lesions (>10 mm)
      were included in the study. A three-phase renal CT, without nephrographic phase,
      had similar diagnostic ability to a four-phase renal CT in the detection and
      characterization of renal lesions. A three-phase CT (plain, corticomedullary, and
      excretory phase) is therefore adequate in the clinical diagnosis of renal
      lesions. 

PMID- 24035805
TI  - Functional diversity of the p24gamma homologue Erp reveals physiological
      differences between two filamentous fungi.
AB  - The protein hyper-secreting filamentous fungi impact their surrounding
      environments by secreting cellulases and digesting plant cell wall via microbe
      plant interspecies interaction. This process is of paramount importance in
      biofuel production from the renewable lignocellulosic biomass, because cellulase
      production is the key factor in cost determination. Despite the importance of
      protein secretion, p24 protein, a key factor in eukaryotic protein maturation and
      secretion, was never investigated in filamentous fungi. The erp genes encoding
      p24gamma homologues were identified in Trichoderma reesei and Penicillium
      decumbens. The roles of Erp and their participated cellular pathways were
      investigated via disruption of erp, revealing significant differences:
      sporulation was hampered in T. reesei Deltaerp but not in P. decumbens Deltaerp;
      in both species Erp maintains membrane integrity; Erp is likely involved in
      hyphae polarity maintenance in T. reesei. Protein- and transcription-level
      investigations of Erp participation in cellulase production revealed distinct
      regulatory mechanisms. In T. reesei, cellulase encoding genes were repressed
      under secretion stress. In contrast, activation of the same genes under the same
      stress was identified in P. decumbens. These observations revealed a novel
      cellulase gene regulation mechanism, clearly suggested the different
      physiological roles of Erp, and further demonstrated the different physiology of
      T. reesei and P. decumbens, despite above 75% sequence identity between the
      proteins and the close evolutionary relationship between the two species. 

PMID- 24035806
TI  - Introduction to special issue: 'neuroethics and neurodegenerative disease'.

PMID- 24035804
TI  - Viral channel proteins in intracellular protein-protein communication: Vpu of HIV
      1, E5 of HPV16 and p7 of HCV.
AB  - Viral channel forming proteins are known for their capability to make the lipid
      membrane of the host cell and its subcellular compartments permeable to ions and
      small compounds. There is increasing evidence that some of the representatives of
      this class of proteins are also strongly interacting with host proteins and the
      effectiveness of this interaction seems to be high. Interaction of viral channel
      proteins with host factors has been proposed by bioinformatics approaches and has
      also been identified experimentally. An overview of the interactions with host
      proteins is given for Vpu from HIV-1, E5 from HPV-16 and p7 from HCV. This
      article is part of a Special Issue entitled: Viral Membrane Proteins - Channels
      for Cellular Networking. 

PMID- 24035807
TI  - Specific qPCR assays for the detection of orf virus, pseudocowpox virus and
      bovine papular stomatitis virus.
AB  - The genus Parapoxvirus (PAPV) is comprised traditionally of orf virus (ORFV),
      pseudocowpox virus (PCPV) and bovine papular stomatitis virus (BPSV), which cause
      infections of ruminants and their handlers in the U.S. and worldwide. Unlike
      orthopoxvirus infections, which can cause systemic or localized infections, PAPV
      infections present normally as benign, self-limited and localized skin lesions;
      infections do not confer lifelong immunity. In recent years, related potentially
      to enhanced awareness and the availability of diagnostic methods, there has been
      an observed increase in reported cases of PAPV in animals and humans. This study
      describes TaqMan based real-time PCR assays for both generic and specific
      detection of PAPV species for surveillance and outbreak investigations. These
      assays target highly conserved PAPV RNA polymerase gene sequences and are capable
      of detecting three known species of PAPVs (ORFV, PCPV, and BPSV). The assays were
      evaluated using a panel of PAPV DNA derived from human infections or animal
      specimen remainders. The sensitivities of all four assays were determined using
      droplet digital PCR; fewer than 10 copies of clinical PAPV DNA can be detected
      consistently. These assays provide a reliable and sensitive method for rapid
      confirmation and characterization PAPV infections with varying clinical
      presentations. 

PMID- 24035808
TI  - Synthesis and antibacterial activity of new long-chain-alkyl bile acid-based
      amphiphiles.
AB  - The efficient synthesis of some bile acid-derived cationic amphiphiles with a
      flexible long hydrocarbon tail was investigated. Firstly, the modification on the
      side-chain carboxyl of bile acids was carried out efficiently by one-pot
      amidation of bile acids and a long-chain aliphatic amine in the presence of HOBt
      and DCC to introduce a flexible long hydrocarbon tail. Then the hydrophilic
      concave side of bile acids with hydroxyl groups was further modified into
      cationic groups for strengthening hydrophilicity. This strategy offered a very
      straightforward and efficient method for access to the designed amphiphiles in
      good overall yields. The preliminary results showed that an increase both in the
      length of the hydrophobic tail and in the number of charged groups resulted in a
      decrease in the CMC of bile acid-derived cationic amphiphiles. And the bile acid
      derived cationic amphiphiles with a flexible longer hydrocarbon tail and more
      positive charges had the highest antibacterial and antimicrobial activity. 

PMID- 24035809
TI  - Demyelination and other neurological adverse events after anti-TNF therapy.
AB  - Tumor necrosis factor (TNF) alpha inhibitors are an essential therapeutic option
      for several inflammatory diseases, like rheumatoid arthritis,
      spondyloarthropathies and inflammatory bowel diseases. As TNFalpha antagonists
      have become increasingly utilized, there have been a number of reports of
      neurological adverse events in patients receiving anti-TNFalpha therapy. The
      frequency of central nervous system adverse events after initiation of anti
      TNFalpha therapy is unknown. However, questions have been raised about a possible
      causal association. Although several hypotheses have been proposed in an attempt
      to explain the possible relationship between TNFalpha antagonist and
      demyelination, none is considered to be adequate. Thus, in this report we deal
      with the implication of TNFalpha in multiple sclerosis and we discuss the
      possible relationship of TNFalpha antagonist and demyelinating diseases. 

PMID- 24035810
TI  - Eco-geographical differentiation among Colombian populations of the Chagas
      disease vector Triatoma dimidiata (Hemiptera: Reduviidae).
AB  - Triatoma dimidiata is currently the main vector of Chagas disease in Mexico, most
      Central American countries and several zones of Ecuador and Colombia. Although
      this species has been the subject of several recent phylogeographic studies, the
      relationship among different populations within the species remains unclear. To
      elucidate the population genetic structure of T. dimidiata in Colombia, we
      analyzed individuals from distinct geographical locations using the cytochrome c
      oxidase subunit 1 gene and 7 microsatellite loci. A clear genetic differentiation
      was observed among specimens from three Colombian eco-geographical regions: Inter
      Andean Valleys, Caribbean Plains and Sierra Nevada de Santa Marta mountain
      (SNSM). Additionally, evidence of genetic subdivision was found within the
      Caribbean Plains region as well as moderate gene flow between the populations
      from the Caribbean Plains and SNSM regions. The genetic differentiation found
      among Colombian populations correlates, albeit weakly, with an isolation-by
      distance model (IBD). The genetic heterogeneity among Colombian populations
      correlates with the eco-epidemiological and morphological traits observed in this
      species across regions within the country. Such genetic and epidemiological
      diversity should be taken into consideration for the development of vector
      control strategies and entomological surveillance. 

PMID- 24035811
TI  - High frequency of HIV-1 infections with multiple HIV-1 strains in men having sex
      with men (MSM) in Senegal.
AB  - Circulating and unique recombinant HIV-1 strains continue to be identified and
      their number increases over time, suggesting that co-infection with multiple HIV
      1 is frequent. In this study we analyzed to what extent dual infections with
      different HIV-1 variants occur in a population group with high risk behaviour,
      high HIV-1 prevalence and in an area where multiple HIV-1 subtypes and
      Circulating Recombinant Forms (CRFs) co-circulate. We studied 69 MSM with our
      recently developed multi-region hybridization assay (MHA), based on fluorescent
      probe detection for eight common variants circulating in West and West Central
      Africa. At least 11 (15.9%) of the 69 patients were simultaneously infected with
      two different HIV-1 subtypes and/or CRFs. Among the 29 samples identified as
      subtype C by MHA in gag, 15 (57.7%) reacted with both C1 and C2 probes. Sequence
      analysis suggests that the majority of the samples reactive with C1 and C2 probes
      are most likely infected with two different subtype C clades. Single genome
      amplification and DNA dilutions confirmed dual infection with subtype D and C for
      MSM1193, triple infection with two different C subtype strains and one CRF02_AG
      strain in MSM1157 and showed that MSM3017 is at least co-infected with CRF06_cpx
      and CRF02_AG and another strain that could not be classified. Comparison of all
      subtype C sequences from the MSM population and from the general population from
      this and previous studies confirmed the intermixing of HIV-1 variants between low
      risk women and high-risk men as shown by the intermixing of subtype C variants
      from MSM1157 and a female patient (02SN-HALD478). Comparison of dual infection
      rates between the general population and MSM in Senegal, show also clearly the
      importance of high HIV prevalence and high risk behavior in dual infections and
      subsequent intermixing of HIV-1 variants which can lead to emergence and spread
      of new recombinants (CRFs). 

PMID- 24035812
TI  - Assembly and distributive action of an archaeal DNA polymerase holoenzyme.
AB  - The assembly and enzymatic ability of the replication DNA polymerase holoenzyme
      from Sulfolobus solfataricus (Sso) was investigated using presteady-state
      fluorescence resonance energy transfer assays coupled with functional and
      structural studies. Kinetic experiments reveal that ATP binding to replication
      factor C (RFC) is sufficient for loading the heterotrimeric PCNA123
      [proliferating cell nuclear antigen (PCNA)] clamp onto DNA that includes a rate
      limiting conformational rearrangement of the complex. ATP hydrolysis is required
      for favorable recruitment and interactions with the replication polymerase
      (PolB1) that most likely include clamp closing and RFC dissociation.
      Surprisingly, the assembled holoenzyme complex synthesizes DNA distributively and
      with low processivity, unlike most other well-characterized DNA polymerase
      holoenzyme complexes. We show that PolB1 repeatedly disengages from the DNA
      template, leaving PCNA123 behind. Interactions with a newly identified C-terminal
      PCNA-interacting peptide (PIP) motif on PolB1 specifically with PCNA2 are
      required for holoenzyme formation and continuous re-recruitment during synthesis.
      The extended tail-like structure of the C-terminal PIP motif in PolB1 is revealed
      alone and when bound to DNA using small-angle X-ray scattering allowing us to
      develop a model for the holoenzyme complex. This is the first detailed kinetic
      description of clamp loading and holoenzyme assembly in crenarchaea and has
      revealed a novel mode for dynamic processivity that occurs by a polymerase
      exchange mechanism. This work has important implications for processive DNA
      replication synthesis and also suggests a potential mechanism for polymerase
      switching to bypass lesions. 

PMID- 24035813
TI  - Crystal structure of the bacteriophage Qbeta coat protein in complex with the RNA
      operator of the replicase gene.
AB  - The coat proteins of single-stranded RNA bacteriophages specifically recognize
      and bind to a hairpin structure in their genome at the beginning of the replicase
      gene. The interaction serves to repress the synthesis of the replicase enzyme
      late in infection and contributes to the specific encapsidation of phage RNA.
      While this mechanism is conserved throughout the Leviviridae family, the coat
      protein and operator sequences from different phages show remarkable variation,
      serving as prime examples for the co-evolution of protein and RNA structure. To
      better understand the protein-RNA interactions in this virus family, we have
      determined the three-dimensional structure of the coat protein from bacteriophage
      Qbeta bound to its cognate translational operator. The RNA binding mode of Qbeta
      coat protein shares several features with that of the widely studied phage MS2,
      but only one nucleotide base in the hairpin loop makes sequence-specific contacts
      with the protein. Unlike in other RNA phages, the Qbeta coat protein does not
      utilize an adenine-recognition pocket for binding a bulged adenine base in the
      hairpin stem but instead uses a stacking interaction with a tyrosine side chain
      to accommodate the base. The extended loop between beta strands E and F of Qbeta
      coat protein makes contacts with the lower part of the RNA stem, explaining the
      greater length dependence of the RNA helix for optimal binding to the protein.
      Consequently, the complex structure allows the proposal of a mechanism by which
      the Qbeta coat protein recognizes and discriminates in favor of its cognate RNA. 

PMID- 24035814
TI  - An enzyme-catalysed bleaching treatment to meet dissolving pulp characteristics
      for cellulose derivatives applications.
AB  - Bleached cellulose with good end-properties (~ 90% ISO brightness and 62%
      cellulose preservation) was obtained by using a totally chlorine-free
      biobleaching process (TCF). Unbleached sulphite cellulose was treated with
      Trametes villosa laccase in combination with violuric acid. This enzymatic stage
      (L) was followed by a chelating stage (Q) and then by a hydrogen peroxide stage
      reinforced with pressurized oxygen (Po), resulting to an overall LQPo sequence.
      The use of violuric acid was dictated by the results of a preliminary study,
      where the bleaching efficiency of various natural (syringaldehyde and p-coumaric
      acid) and synthetic mediators (violuric acid and 1-hydroxybenzotriazole) were
      assessed. The outstanding results obtained with laccase-violuric acid system
      fulfil most of the characteristics of commercial dissolving pulp, totally
      acceptable for viscose manufacturing or CMC derivatives, with the added advantage
      that the enzymatic treatment saved 2h of reaction time and about 70% of hydrogen
      peroxide consumption, relative to a conventional sequence (Po).

PMID- 24035815
TI  - Direct electron transfer from electrode to electrochemically active bacteria in a
      bioelectrochemical dechlorination system.
AB  - Pentachlorophenol (PCP) was dechlorinated by electrochemically active bacteria
      using an electrode as the direct electron donor. Dechlorination efficiency and
      coulombic efficiency (CE) were investigated. When hydrogen evolution reaction was
      eliminated by controlling the potential, both dechlorination efficiency and CE
      increase as the potential decreases, which implied the dechlorination was
      stimulated by electric current rather than hydrogen gas. Further investigation of
      the cyclic voltammetry characterization of the medium revealed nearly no redox
      mediator secreted by the bacteria. Moreover, the comparison of dechlorination
      experiments carried out with filtered and unfiltered medium provided convincible
      evidence that the dominating electron transfer mechanism for the dechlorination
      is direct electron transfer. Additionally, 454 pyrosequencing technique was
      employed to gain a comprehensive understanding of the biocathodic microbial
      community. The results showed Proteobacteria, Bacteroidetes and Firmicutes were
      the three predominant groups. This paper demonstrated the direct electron
      transfer mechanism could be involved in PCP dechlorination with a biocathode. 

PMID- 24035816
TI  - Manipulation of ultrasonic effects on lignocellulose by varying the frequency,
      particle size, loading and stirring.
AB  - The parameters, including ultrasonic frequency, still versus stirring, biomass
      particle size and biomass loading were concurrently investigated for the
      ultrasonic treatment of wheat straw. Experiments were conducted at three
      different frequencies; 40, 376, and 995 kHz using three different solid to liquid
      ratios, 1/50, 1/20, and 1/15(g/ml), with and without mechanical stirring.
      Additional treatments in different particle size ranges, 0-0.5, 0.5-1, and 1-2mm
      were performed at the solid to liquid ratio of 1/20(g/ml). Fractionation was
      improved at 40 and 995 kHz via different mechanisms. Delignification was favored
      at the ultrasonic treatment frequency of 40 kHz, biomass loading 1/20(g/ml) with
      stirring and particle size range of 0.5-1mm. However at 995 kHz carbohydrate
      solubilization was favored, especially in the particle size range of <0.5mm. The
      treatment efficacies highlighted the use of ultrasound for physical and chemical
      effects at different frequencies.

PMID- 24035817
TI  - Bacterial-fungal interactions enhance power generation in microbial fuel cells
      and drive dye decolourisation by an ex situ and in situ electro-Fenton process.
AB  - In this work, the potential for sustainable energy production from wastes has
      been exploited using a combination fungus-bacterium in microbial fuel cell (MFC)
      and electro-Fenton technology. The fungus Trametes versicolor was grown with
      Shewanella oneidensis so that the bacterium would use the networks of the fungus
      to transport the electrons to the anode. This system generated stable electricity
      that was enhanced when the electro-Fenton reactions occurred in the cathode
      chamber. This configuration reached a stable voltage of approximately 1000 mV.
      Thus, the dual benefits of the in situ-designed MFC electro-Fenton, the
      simultaneous dye decolourisation and the electricity generation, were
      demonstrated. Moreover, the generated power was effectively used to drive an ex
      situ electro-Fenton process in batch and continuous mode. This newly developed
      MFC fungus-bacterium with an in situ electro-Fenton system can ensure a high
      power output and a continuous degradation of organic pollutants.

PMID- 24035818
TI  - Experimental study and neural network modeling of sugarcane bagasse pretreatment
      with H2SO4 and O3 for cellulosic material conversion to sugar.
AB  - In this study, pretreatment of sugarcane bagasse and subsequent enzymatic
      hydrolysis is investigated using two categories of pretreatment methods: dilute
      acid (DA) pretreatment and combined DA-ozonolysis (DAO) method. Both methods are
      accomplished at different solid ratios, sulfuric acid concentrations, autoclave
      residence times, bagasse moisture content, and ozonolysis time. The results show
      that the DAO pretreatment can significantly increase the production of glucose
      compared to DA method. Applying k-fold cross validation method, two optimal
      artificial neural networks (ANNs) are trained for estimations of glucose
      concentrations for DA and DAO pretreatment methods. Comparing the modeling
      results with experimental data indicates that the proposed ANNs have good
      estimation abilities. 

PMID- 24035820
TI  - Neural sensitivity to statistical regularities as a fundamental biological
      process that underlies auditory learning: the role of musical practice.
AB  - There is increasing evidence that humans and other nonhuman mammals are sensitive
      to the statistical structure of auditory input. Indeed, neural sensitivity to
      statistical regularities seems to be a fundamental biological property underlying
      auditory learning. In the case of speech, statistical regularities play a crucial
      role in the acquisition of several linguistic features, from phonotactic to more
      complex rules such as morphosyntactic rules. Interestingly, a similar sensitivity
      has been shown with non-speech streams: sequences of sounds changing in frequency
      or timbre can be segmented on the sole basis of conditional probabilities between
      adjacent sounds. We recently ran a set of cross-sectional and longitudinal
      experiments showing that merging music and speech information in song facilitates
      stream segmentation and, further, that musical practice enhances sensitivity to
      statistical regularities in speech at both neural and behavioral levels. Based on
      recent findings showing the involvement of a fronto-temporal network in speech
      segmentation, we defend the idea that enhanced auditory learning observed in
      musicians originates via at least three distinct pathways: enhanced low-level
      auditory processing, enhanced phono-articulatory mapping via the left Inferior
      Frontal Gyrus and Pre-Motor cortex and increased functional connectivity within
      the audio-motor network. Finally, we discuss how these data predict a beneficial
      use of music for optimizing speech acquisition in both normal and impaired
      populations.

PMID- 24035821
TI  - Physicochemical compatibility and stability of nebulizable drug admixtures
      containing Dornase alfa and tobramycin.
AB  - The objective of this in-vitro study was to determine whether admixtures of the
      inhalation solutions Pulmozyme((r)) (Dornase alfa) and either Bramitob((r)) or
      Tobi((r)) (both containing Tobramycin) are physicochemically compatible and to
      analyze the aerodynamic parameters of these admixtures. After mixing, test
      solutions were stored at room temperature and under ambient light conditions over
      a period of 24 h. Tobramycin concentrations were determined by using a
      fluorescence immunoassay. Stability of dornase alfa was determined by size
      exclusion high performance liquid chromatography, ultraviolet spectroscopy,
      sodium dodecyl sulfate polyacrylamide gel electrophoresis and tentacle strong
      cation-exchange chromatography. In addition, pH values and osmolality of the
      admixtures were measured and test solutions were visually examined for any
      changes up to 24 h. Aerosols of Pulmozyme((r))/Bramitob((r)) or
      Pulmozyme((r))/TOBI((r)) admixtures were generated with the PARI eFlow((r)) rapid
      and aerodynamic particle sizing was performed via cascade impaction with the Next
      Generation Pharmaceutical Impactor. The stability tests revealed that neither the
      stability of tobramycin nor the stability of dornase alfa was affected by mixing
      the inhalation products. Cascade impaction showed no relevant changes in particle
      size distribution, Mass Median Aerodynamic Diameter, Geometric Standard Deviation
      and Fine Particle Fraction in comparison to aerodynamic parameters of the unmixed
      solutions. Thus, admixtures of Pulmozyme((r)) and either Bramitob((r)) or
      TOBI((r)) can be designated as compatible for a 24 h period and simultaneous
      inhalation is feasible.

PMID- 24035819
TI  - Syllabic (~2-5 Hz) and fluctuation (~1-10 Hz) ranges in speech and auditory
      processing.
AB  - Given recent interest in syllabic rates (~2-5 Hz) for speech processing, we
      review the perception of "fluctuation" range (~1-10 Hz) modulations during
      listening to speech and technical auditory stimuli (AM and FM tones and noises,
      and ripple sounds). We find evidence that the temporal modulation transfer
      function (TMTF) of human auditory perception is not simply low-pass in nature,
      but rather exhibits a peak in sensitivity in the syllabic range (~2-5 Hz). We
      also address human and animal neurophysiological evidence, and argue that this
      bandpass tuning arises at the thalamocortical level and is more associated with
      non-primary regions than primary regions of cortex. The bandpass rather than low
      pass TMTF has implications for modeling auditory central physiology and speech
      processing: this implicates temporal contrast rather than simple temporal
      integration, with contrast enhancement for dynamic stimuli in the fluctuation
      range. This article is part of a Special Issue entitled "Communication Sounds and
      the Brain: New Directions and Perspectives". 

PMID- 24035822
TI  - Estrogen replacement therapy and asthma.
AB  - A growing body of clinical and experimental evidence indicates that female sex
      hormones, particularly estrogen, have significant effects on normal airway
      function as well as on respiratory disorders, such as asthma. These effects are
      very complex and are exerted at several levels, directly on airway reactivity or
      indirectly through regulation of the immune and inflammatory responses in the
      lung. They can have relevant clinical implications not only according to the
      phases of the reproductive life in women, but also in relation to the
      therapeutical administration of estrogen, as in the case of menopausal hormone
      therapy. Clinical evidence suggests that administration of estrogen to menopausal
      women is associated with increased rates of newly diagnosed asthma. Conversely,
      functional studies show that estrogen can improve objective indexes of
      respiratory functionality. 

PMID- 24035823
TI  - Preclinical safety profile of trastuzumab emtansine (T-DM1): mechanism of action
      of its cytotoxic component retained with improved tolerability.
AB  - Trastuzumab emtansine (T-DM1) is the first antibody-drug conjugate (ADC) approved
      for patients with human epidermal growth factor receptor 2 (HER2)-positive
      metastatic breast cancer. The therapeutic premise of ADCs is based on the
      hypothesis that targeted delivery of potent cytotoxic drugs to tumors will
      provide better tolerability and efficacy compared with non-targeted delivery,
      where poor tolerability can limit efficacious doses. Here, we present results
      from preclinical studies characterizing the toxicity profile of T-DM1, including
      limited assessment of unconjugated DM1. T-DM1 binds primate ErbB2 and human HER2
      but not the rodent homolog c-neu. Therefore, antigen-dependent and non-antigen
      dependent toxicity was evaluated in monkeys and rats, respectively, in both
      single- and repeat-dose studies; toxicity of DM1 was assessed in rats only. T-DM1
      was well tolerated at doses up to 40 mg/kg (~4400 MUg DM1/m(2)) and 30 mg/kg (~
      6000 MUg DM1/m(2)) in rats and monkeys, respectively. In contrast, DM1 was only
      tolerated up to 0.2mg/kg (1600 MUg DM1/m(2)). This suggests that at least two
      fold higher doses of the cytotoxic agent are tolerated in T-DM1, supporting the
      premise of ADCs to improve the therapeutic index. In addition, T-DM1 and DM1
      safety profiles were similar and consistent with the mechanism of action of DM1
      (i.e., microtubule disruption). Findings included hepatic, bone
      marrow/hematologic (primarily platelet), lymphoid organ, and neuronal toxicities,
      and increased numbers of cells of epithelial and phagocytic origin in metaphase
      arrest. These adverse effects did not worsen with chronic dosing in monkeys and
      are consistent with those reported in T-DM1-treated patients to date.

PMID- 24035825
TI  - On the resemblance of synapse formation and CNS myelination.
AB  - The myelination of axons in the central nervous system (CNS) is essential for
      nervous system formation, function and health. CNS myelination continues well
      into adulthood, but not all axons become myelinated. Unlike the peripheral
      nervous system, where we know of numerous axon-glial signals required for
      myelination, we have a poor understanding of the nature or identity of such
      molecules that regulate which axons are myelinated in the CNS. Recent studies
      have started to elucidate cell behavior during myelination in vivo and indicate
      that the choice of which axons are myelinated is made prior to myelin sheath
      generation. Here we propose that interactions between axons and the exploratory
      processes of oligodendrocyte precursor cells (OPCs) lead to myelination and may
      be similar to those between dendrites and axons that prefigure and lead to
      synapse formation. Indeed axons and OPCs form synapses with striking resemblance
      to those of neurons, suggesting a similar mode of formation. We discuss families
      of molecules with specific functions at different stages of synapse formation and
      address studies that implicate the same factors during axon-OPC synapse formation
      and myelination. We also address the possibility that the function of such
      synapses might directly regulate the myelinating behavior of oligodendrocyte
      processes in vivo. In the future it may be of benefit to consider these
      similarities when taking a candidate-based approach to dissect mechanisms of CNS
      myelination. 

PMID- 24035824
TI  - New insights to the role of aryl hydrocarbon receptor in bone phenotype and in
      dioxin-induced modulation of bone microarchitecture and material properties.
AB  - Bone is a target for high affinity aryl hydrocarbon receptor (AHR) ligands, such
      as dioxins. Although bone morphology, mineral density and strength are sensitive
      endpoints of dioxin toxicity, less is known about effects on bone
      microarchitecture and material properties. This study characterizes TCDD-induced
      modulations of bone tissue, and the role of AHR in dioxin-induced bone toxicity
      and for normal bone phenotype. Six AHR-knockout (Ahr(-/-)) and wild-type
      (Ahr(+/+)) mice of both genders were exposed to TCDD weekly for 10 weeks, at a
      total dose of 200MUg/kgbw. Bones were examined with micro-computed tomography,
      nanoindentation and biomechanical testing. Serum levels of bone remodeling
      markers were analyzed, and the expression of genes related to osteogenic
      differentiation was profiled using PCR array. In Ahr(+/+) mice, TCDD-exposure
      resulted in harder bone matrix, thinner and more porous cortical bone, and a more
      compact trabecular bone compartment. Bone remodeling markers and altered
      expression of a number of osteogenesis related genes indicated imbalanced bone
      remodeling. Untreated Ahr(-/-) mice displayed a slightly modified bone phenotype
      as compared with untreated Ahr(+/+) mice, while TCDD exposure caused only a few
      changes in bones of Ahr(-/-) mice. Part of the effects of both TCDD-exposure and
      AHR-deficiency were gender dependent. In conclusion, exposure of adult mice to
      TCDD resulted in harder bone matrix, thinner cortical bone, mechanically weaker
      bones and most notably, increased trabecular bone volume fraction in Ahr(+/+)
      mice. AHR is involved in bone development of a normal bone phenotype, and is
      crucial for manifestation of TCDD-induced bone alterations.

PMID- 24035827
TI  - Response properties of local field potentials and multiunit activity in the mouse
      visual cortex.
AB  - Extracellular local field potentials (LFPs) and multiunit activity (MUA) reflect
      the spatially integrated activity of multiple neurons in a given cortical
      structure. In the cat and primate visual cortices, these signals exhibit
      selectivity for visual stimulus features, such as orientation, direction of
      motion or spatial frequency. In the mouse visual cortex, a model which has been
      increasingly used in visual neuroscience, the visual stimulus selectivity of
      population signals has not been examined in detail. We recorded LFPs and MUA
      using multielectrode arrays and two derived measures, the high-pass filtered
      continuous MUA and the bipolar first spatial derivative of the LFP, in the visual
      cortex of isoflurane-anesthetized C57Bl/6 mice. We analyzed the onset latency and
      characterized the receptive fields in addition to the direction, orientation, and
      spatial and temporal frequency preferences of these signals. Population signals
      exhibited onset latencies as short as ~30ms and possessed receptive fields as
      large as ~38 degrees  with MUA receptive fields smaller than those of LFPs. All
      four population signals exhibited similar spatial frequency preferences (~0.1
      cycles per degree) and temporal frequency preferences (~1 cycle per second).
      However, for all population signals, spatial and frequency tunings were broad and
      orientation and direction of motion preferences were absent. The characterization
      of the visual stimulus selectivity of LFPs and MUA in the mouse visual cortex
      should provide information regarding their usability in characterizing stimulus
      properties and disclose possible limitations. 

PMID- 24035826
TI  - Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated
      excitatory neurotransmission and plasticity.
AB  - Endocannabinoids (eCBs) are involved in the stress response and alterations in
      eCB signaling may contribute to the etiology of mood disorders. Exposure to
      chronic mild stress (CMS), a model of depression, produces downregulation of the
      cannabinoid 1 (CB1) receptor in the hippocampus of male rats. However, it is
      unknown how this stress-induced change in CB1 levels affects eCB-mediated
      neurotransmission. In vitro, field potential recordings from CMS-exposed (21
      days) rats were performed to assess the effects of stress on eCB-regulated
      glutamatergic neurotransmission in/on hippocampal area CA1. We observed that
      application of the CB1 agonist, WIN 55,212-5 (1 MUM), in stress animals resulted
      in a ~135% increase in excitatory neurotransmission, whereas CB1 activation in
      non-stress animals leads to a ~30% decrease. However, during blockade of GABA(A)
      neurotransmission with picrotoxin, CB1 activation yielded a ~35% decrease in
      stress animals. These findings indicate that CMS does not directly affect
      glutamatergic neurotransmission. Rather, CMS sensitizes CB1 function on GABAergic
      terminals, leading to less inhibition and an increase in excitatory
      neurotransmission. This finding is reinforced in that induction of weak long-term
      potentiation (LTP) is enhanced in CMS-exposed animals compared to controls and
      this enhancement is CB1-dependent. Lastly, we observed that the LTP-blocking
      property of WIN 55,212-5 shifts from being glutamate-dependent in non-stress
      animals to being GABA-dependent in stress animals. These results effectively
      demonstrate that CMS significantly alters hippocampal eCB-mediated
      neurotransmission and synaptic plasticity.

PMID- 24035829
TI  - Prism adaptation and neck muscle vibration in healthy individuals: are two
      methods better than one?
AB  - Studies involving therapeutic combinations reveal an important benefit in the
      rehabilitation of neglect patients when compared to single therapies. In light of
      these observations our present work examines, in healthy individuals,
      sensorimotor and cognitive after-effects of prism adaptation and neck muscle
      vibration applied individually or simultaneously. We explored sensorimotor after
      effects on visuo-manual open-loop pointing, visual and proprioceptive straight
      ahead estimations. We assessed cognitive after-effects on the line bisection
      task. Fifty-four healthy participants were divided into six groups designated
      according to the exposure procedure used with each: 'Prism' (P) group; 'Vibration
      with a sensation of body rotation' (Vb) group; 'Vibration with a move illusion of
      the LED' (Vl) group; 'Association with a sensation of body rotation' (Ab) group;
      'Association with a move illusion of the LED' (Al) group; and 'Control' (C)
      group. The main findings showed that prism adaptation applied alone or combined
      with vibration showed significant adaptation in visuo-manual open-loop pointing,
      visual straight-ahead and proprioceptive straight-ahead. Vibration alone produced
      significant after-effects on proprioceptive straight-ahead estimation in the Vl
      group. Furthermore all groups (except C group) showed a rightward neglect-like
      bias in line bisection following the training procedure. This is the first
      demonstration of cognitive after-effects following neck muscle vibration in
      healthy individuals. The simultaneous application of both methods did not produce
      significant greater after-effects than prism adaptation alone in both
      sensorimotor and cognitive tasks. These results are discussed in terms of
      transfer of sensorimotor plasticity to spatial cognition in healthy individuals. 

PMID- 24035830
TI  - A cost-effective system for in-situ geological arsenic adsorption from
      groundwater.
AB  - An effective and low-cost in-situ geological filtration system was developed to
      treat arsenic-contaminated groundwater in remote rural areas. Hangjinhouqi in
      western Hetao Plain of Inner Mongolia, China, where groundwater contains a high
      arsenic concentration, was selected as the study area. Fe-mineral and limestone
      widely distributed in the study area were used as filter materials. Batch and
      column experiments as well as field tests were performed to determine optimal
      filtration parameters and to evaluate the effectiveness of the technology for
      arsenic removal under different hydrogeochemical conditions. A mixture containing
      natural Fe-mineral (hematite and goethite) and limestone at a mass ratio of 2:1
      was found to be the most effective for arsenic removal. The results indicated
      that Fe-mineral in the mixture played a major role for arsenic removal.
      Meanwhile, limestone buffered groundwater pH to be conducive for the optimal
      arsenic removal. As(III) adsorption and oxidation by iron mineral, and the
      formation of Ca-As(V) precipitation with Ca contributed from limestone
      dissolution were likely mechanisms leading to the As removal. Field
      demonstrations revealed that a geological filter bed filled with the proposed
      mineral mixture reduced groundwater arsenic concentration from 400 MUg/L to below
      10 MUg/L. The filtration system was continuously operated for a total volume of
      365,000L, which is sufficient for drinking water supplying a rural household of 5
      persons for 5 years at a rate of 40 L per person per day.

PMID- 24035828
TI  - Matrix metalloproteinase-2 deletions protect against hemorrhagic transformation
      after 1 h of cerebral ischemia and 23 h of reperfusion.
AB  - Although elevated matrix metalloproteinase (MMP)-2 levels were highly related to
      the degradation of tight junction (TJ) proteins and basal lamina and neuronal
      injury after ischemia, until very recently, little experimental evidence was
      available to test the role of the MMP-2 knockout (KO) in blood-brain-barrier
      (BBB) injury and the development of hemorrhage transformation (HT). Here, we
      assessed the role of the MMP-2 KO in BBB injury, HT and other brain injuries
      after 1h of ischemia and 23 h of reperfusion. Middle cerebral artery occlusion
      (MCAO) was performed in MMP-2 KO mice. Reperfusion was started 1h after the onset
      of MCAO. All mice were sacrificed 24h after the MCAO. MMP-2 deficiency reduced
      the decrease in protein levels of collagen IV and cellular membrane occludin
      (p<0.01 and 0.05 vs. wild-type (WT), respectively) and attenuated increase in
      cytosol occludin level in ischemic brain (p<0.01 vs. WT). The hemorrhage volume
      and brain infarction were significantly decreased in both the cortex and striatum
      in the MMP-2 KO mice (p<0.01 vs. WT). The MMP-2 KO also had reduced brain
      swelling in the cortex and improved neurological deficits (p<0.01 vs. WT). These
      studies provide direct evidence that targeting MMP-2 will effectively protect
      against collagen and occludin loss and HT after ischemia and reperfusion.

PMID- 24035831
TI  - Physiological changes of a green alga (Micractinium sp.) involved in an early
      stage of association with Tetrahymena thermophila during 5-year microcosm
      culture.
AB  - Endosymbioses between phototrophic algae and heterotrophic organisms are an
      important symbiotic association in that this association connects photo- and
      heterotrophic metabolism, and therefore, affects energy/matter pathways and
      cycling in the ecosystem. However, little is known about the early processes of
      evolution of an endosymbiotic association between previously non-associated
      organisms. In previous studies, we analyzed an early process of the evolution of
      an endosymbiotic association between an alga and a ciliate by using a long-term
      culture of an experimental model ecosystem (CET microcosm) composed of a green
      alga (Micractinium sp.), a bacterium (Escherichia coli), and a ciliate
      (Tetrahymena thermophila). The results revealed that an algal type, isolated from
      5-year cultures of the microcosm, prolonged the longevity of the ancestral and
      derived clones of T. thermophila in the absence of bacteria, suggesting that a
      cooperative algal phenotype that benefited the ciliate had evolved in the
      microcosm. Here, we investigated the physiological changes of the derived
      Micractinium clones that benefited Tetrahymena, focusing on the release of
      carbohydrates by and abundance of photopigments in the ancestral and 2 derived
      algal clones (SC10-2 and SC9-1) isolated from inside Tetrahymena cells. Analyses
      using HPLC revealed that the algal isolates released glycerol and sucrose at
      higher concentrations per cell and also contained higher levels of photopigments
      per cell at pH 7.2, in comparison with the ancestral strain. These phenotypic
      characters were considered responsible for the increased longevity of Tetrahymena
      cells, and thus supported the cooperator alga hypothesis. 

PMID- 24035832
TI  - A modeled dynamic regulatory network of NF-kappaB and IL-6 mediated by miRNA.
AB  - The inflammatory response is a rapid and complex physiological reaction to
      infection, which must be carefully modulated to remove pathogens and prevent the
      consequences of unregulated expression including cancer. MiRNAs are small
      noncoding RNAs that regulate protein-coding genes via post-transcriptional
      repression. Emerging evidence suggests that the role of miRNAs in the regulation
      of immune responses as well as inflammatory networks in various cell and tissue
      types. Here, we have constructed a mathematical model that integrates miR-21 and
      miR-146 expression into a signaling pathway to generate an in silico model for
      the process of inflammation. The results show that the negative feedback provided
      by miR-21 stimulates the propensity of oscillations in NF-kappaB and IL-6
      activity, while the negative feedback provided by miR-146 dampens the
      oscillations of NF-kappaB and IL-6. This process is somewhat sensitive to the
      inputs of miR-21 and miR-146, suggesting that variations in the relative strength
      of the two feedbacks may provide for altered response dynamics to the same
      stimulus. Our findings reveal a novel regulatory module of two miRNA-mediated
      negative feedback loops that allows for the fine-tuning of the dynamics of key
      mediators in inflammation. 

PMID- 24035833
TI  - The DEAD-box RNA helicase DDX5 acts as a positive regulator of Japanese
      encephalitis virus replication by binding to viral 3' UTR.
AB  - Japanese encephalitis virus (JEV), one of the causes for epidemic encephalitis,
      belongs to the family of Flaviviridae. In this study, we demonstrated that
      cellular DEAD-box RNA helicase DDX5 plays an important role in JEV replication.
      The knockdown of DDX5 was able to decrease JEV replication, and overexpression of
      DDX5 mutants lacking the helicase activity also reduced JEV replication,
      suggesting the helicase activity is essential for JEV replication. DDX5 knockdown
      did not affect virus assembly and release. GST-pulldown and co
      immunoprecipitation experiments demonstrated that DDX5 could interact with JEV
      core protein, non-structural protein 3 (NS3) and 5 (NS5-MTase and NS5-RdRp
      domains). Meanwhile, we also confirmed that DDX5 interacts with these viral
      proteins during JEV infection. Confocal microscopy analysis showed that
      endogenous DDX5 is recruited to the cytoplasm and colocalizes with these viral
      proteins and viral RNA. RNA-pulldown experiment showed that DDX5 only binds to
      the JEV 3' untranslated region (UTR). Finally, we confirmed the role of DDX5 in
      JEV RNA replication using JEV-replicon system. In conclusion, we identified DDX5
      as a positive regulator for JEV replication. 

PMID- 24035834
TI  - Identification of novel small compounds that restore E-cadherin expression and
      inhibit tumor cell motility and invasiveness.
AB  - Tumor dissemination and invasive behavior are associated with a majority of
      cancer-related mortality cases. Loss of E-cadherin, which is caused by several
      tumor-promoting factors, is associated with metastasis and poor prognosis in many
      neoplasms. In this study, we aimed to identify small molecule compounds that
      restore the expression of E-cadherin, because these molecules are most likely to
      suppress tumor malignancy by restoring E-cadherin function and/or by inhibiting
      signals that suppress E-cadherin expression. Here, we developed a fluorescence
      screen system based on E-cadherin expression. A pilot drug library screen
      revealed that methotrexate (MTX) strongly induces E-cadherin expression in a
      colorectal cancer cell line, SW620. From the screen for 9600 compounds, we
      identified 9 hit compounds, which restored the expression of E-cadherin in SW620
      and/or a melanoma cell line, SK-MEL-28. We confirmed that MTX and the other
      identified compounds transcriptionally promote E-cadherin expression. Among
      these, 2 compounds suppressed migration/invasion capacity in colorectal cancer
      cells and 3 in melanoma cells. A compound reduced SW620 migration and invasion
      with subtle effects on cell viability in SW620, SK-MEL-28, and a non-tumor cell
      line, HaCaT, with decrease in AKT and ERK1/2 protein levels. One of the other
      compounds reduced SK-MEL-28 cell migration and invasion and affected the
      viability only of SW620 and SK-MEL-28 cells but not HaCaT cells. These results
      suggest that these compounds would be attractive lead molecules as anti
      metastasis agents. 

PMID- 24035835
TI  - Cardiorespiratory effects of gap junction blockade in the locus coeruleus in
      unanesthetized adult rats.
AB  - The locus coeruleus (LC) plays an important role in central chemoreception. In
      young rats (P9 or younger), 85% of LC neurons increase firing rate in response to
      hypercapnia vs. only about 45% of neurons from rats P10 or older. Carbenoxolone
      (CARB - gap junction blocker) does not affect the % of LC neurons responding in
      young rats but it decreases the % responding by half in older animals. We
      evaluated the participation of gap junctions in the CO2 ventilatory response in
      unanesthetized adult rats by bilaterally microinjecting CARB (300MUM, 1mM or
      3mM/100nL), glycyrrhizic acid (GZA, CARB analog, 3mM) or vehicle (aCSF -
      artificial cerebrospinal fluid) into the LC of Wistar rats. Bilateral gap
      junction blockade in LC neurons did not affect resting ventilation; however, the
      increase in ventilation produced by hypercapnia (7% CO2) was reduced by ~25%
      after CARB 1mM or 3mM injection (1939.7+/-104.8mLkg(-1)min(-1) for the aCSF group
      and 1468.3+/-122.2mLkg(-1)min(-1) for 1mM CARB, P<0.05; 1939.7+/-104.8mLkg(
      1)min(-1) for the aCSF group and 1540.9+/-68.4mLkg(-1)min(-1) for the 3mM CARB
      group, P<0.05) due largely to a decrease in respiratory frequency. GZA injection
      or CARB injection outside the LC (peri-LC) had no effect on ventilation under any
      conditions. The results suggest that gap junctions in the LC modulate the
      hypercapnic ventilatory response of adult rats. 

PMID- 24035836
TI  - Frequency dependence of capnography in anesthetized rabbits.
AB  - Aspirative capnography may be of help to diagnose early childhood asthma, but
      clinical usefulness in young children is limited by the relatively high
      respiratory rate. This study aimed to characterize the [Formula: see text] time
      course during airway constriction in 8 anesthetized rabbits, artificially
      ventilated at 30, 60 and 80breaths/min. Methacholine was inhaled to double the
      respiratory resistance measured at 8Hz by the forced oscillation technique. The
      capnogram shape changed in response to both methacholine and ventilatory
      frequency. Slope of phase II, the peak of first-order time derivative and trough
      of the second-order time derivative of the [Formula: see text] signal, were
      significantly attenuated after methacholine compared with baseline at all
      breathing rates (p<0.02). Moreover, significant correlations between respiratory
      reactance and resistance were observed with the phase III slope and the angle
      described by phase II and phase III (p<0.01). It is concluded that capnography
      may be useful to identify acute airway changes related to bronchoconstriction,
      even at high breathing frequencies. 

PMID- 24035837
TI  - Some more on preventing congenital heart block.

PMID- 24035838
TI  - Transcatheter aortic valve implantation for severe autograft regurgitation after
      Ross operation.
AB  - The Ross operation is the procedure of choice for aortic valve disease in
      paediatric patients, because of the potential for growth of the pulmonary
      autograft and because anticoagulation is not required. However, early and late
      autograft dilatation and severe aortic regurgitation may occur. Transcatheter
      aortic valve implantation (TAVI) is an effective procedure for treatment of
      severe degenerative aortic stenosis in patients deemed inoperable or high
      surgical risk. Off-label treatment of severe non-calcified aortic regurgitation
      with transcatheter heart valves has occasionally been reported. We describe the
      first case of TAVI for severe aortic regurgitation in a young woman 10 years
      after a Ross operation. The procedure was performed on a compassionate basis
      after the patient was deemed inoperable because of severe reactive pulmonary
      hypertension (95/55/68 mmHg; pulmonary resistance 18.3 UR) and haemodynamic
      compromise. A 29 mm CoreValve (Medtronic, Minneapolis, MN, USA) was implanted. A
      second prosthesis was deployed "valve-in-valve" for residual severe paravalvular
      leak, caused by the peculiar post-surgical anatomy of the left ventricular
      outflow tract. The procedure was successful and the in-hospital course was
      uncomplicated. During follow-up, pulmonary pressure and resistances were
      significantly lowered and at four years the patient showed markedly improved
      exercise tolerance.

PMID- 24035839
TI  - Extracellular digestion during hyposaline exposure in the Dungeness crab, Cancer
      magister, and the blue crab, Callinectes sapidus.
AB  - Extracellular digestive processes were examined in the Dungeness crab, Cancer
      magister and the blue crab, Callinectes sapidus, during hyposaline exposure. Both
      species are found in estuaries as adults, but vary in their ability to balance
      the cardiovascular and respiratory demands of concurrent osmoregulation and
      digestion. The weak osmoregulator, C. magister, is unable to balance the demands
      of osmoregulation and digestion. Concordant with observed decreases in oxygen
      consumption and mechanical digestion, proteolytic digestion within the foregut
      and hepatopancreas was delayed, resulting in a relative reduction of circulating
      amino acids post-feeding in low salinity. In contrast, the efficient
      osmoregulator, C. sapidus, balances the demands of osmoregulation and digestion,
      and mechanical digestion continues unabated in low salinity. Protease activity in
      the gut fluid and hepatopancreas showed either no change or a reduction over
      time. The transport of amino acids into the cells post-feeding is opposed by an
      efflux of amino acids at the cellular level, and resulted in a build up of amino
      acids in the hemolymph. Despite differences in the extracellular responses to low
      salinity exposure following feeding, both species were able to maintain high
      digestive efficiencies. 

PMID- 24035840
TI  - Modeling seasonal behavior changes and disease transmission with application to
      chronic wasting disease.
AB  - Behavior and habitat of wildlife animals change seasonally according to
      environmental conditions. Mathematical models need to represent this seasonality
      to be able to make realistic predictions about the future of a population and the
      effectiveness of human interventions. Managing and modeling disease in wild
      animal populations requires particular care in that disease transmission dynamics
      is a critical consideration in the etiology of both human and animal diseases,
      with different transmission paradigms requiring different disease risk management
      strategies. Since transmission of infectious diseases among wildlife depends
      strongly on social behavior, mechanisms of disease transmission could also change
      seasonally. A specific consideration in this regard confronted by modellers is
      whether the contact rate between individuals is density-dependent or frequency
      dependent. We argue that seasonal behavior changes could lead to a seasonal shift
      between density and frequency dependence. This hypothesis is explored in the case
      of chronic wasting disease (CWD), a fatal disease that affects deer, elk and
      moose in many areas of North America. Specifically, we introduce a strategic CWD
      risk model based on direct disease transmission that accounts for the seasonal
      change in the transmission dynamics and habitats occupied, guided by information
      derived from cervid ecology. The model is composed of summer and winter
      susceptible-infected (SI) equations, with frequency-dependent and density
      dependent transmission dynamics, respectively. The model includes impulsive birth
      events with density-dependent birth rate. We determine the basic reproduction
      number as a weighted average of two seasonal reproduction numbers. We
      parameterize the model from data derived from the scientific literature on CWD
      and deer ecology, and conduct global and local sensitivity analyses of the basic
      reproduction number. We explore the effectiveness of different culling strategies
      for the management of CWD: although summer culling seems to be an effective
      disease eradication strategy, the total culling rate is limited by the
      requirement to preserve the herd. 

PMID- 24035841
TI  - Does the Australian desert ant Melophorus bagoti approximate a Levy search by an
      intrinsic bi-modal walk?
AB  - We suggest that the Australian desert ant Melophorus bagoti approximates a Levy
      search pattern by using an intrinsic bi-exponential walk and does so when a Levy
      search pattern is advantageous. When attempting to locate its nest, M. bagoti
      adopt a stereotypical search pattern. These searches begin at the location where
      the ant expects to find the nest, and comprise loops that start and end at this
      location, and are directed in different azimuthal directions. Loop lengths are
      exponentially distributed when searches are in visually familiar surroundings and
      are well described by a mixture of two exponentials when searches are in
      unfamiliar landscapes. The latter approximates a power-law distribution, the
      hallmark of a Levy search. With the aid of a simple analytically tractable
      theory, we show that an exponential loop-length distribution is advantageous when
      the distance to the nest can be estimated with some certainty and that a bi
      exponential distribution is advantageous when there is considerable uncertainty
      regarding the nest location. The best bi-exponential search patterns are shown to
      be those that come closest to approximating advantageous Levy looping searches.
      The bi-exponential search patterns of M. bagoti are found to approximate
      advantageous Levy search patterns. 

PMID- 24035842
TI  - Predicting anticancer peptides with Chou's pseudo amino acid composition and
      investigating their mutagenicity via Ames test.
AB  - Cancer is an important reason of death worldwide. Traditional cytotoxic
      therapies, such as radiation and chemotherapy, are expensive and cause severe
      side effects. Currently, design of anticancer peptides is a more effective way
      for cancer treatment. So there is a need to develop a computational method for
      predicting the anticancer peptides. In the present study, two methods have been
      developed to predict these peptides using support vector machine (SVM) as a
      powerful machine learning algorithm. Classifiers have been applied based on the
      concept of Chou's pseudo-amino acid composition (PseAAC) and local alignment
      kernel. Since a number of HIV-1 proteins have cytotoxic effect, therefore we
      predicted the anticancer effect of HIV-1 p24 protein with these methods. After
      the prediction, mutagenicity of 2 anticancer peptides and 2 non-anticancer
      peptides was investigated by Ames test. Our results show that, the accuracy and
      the specificity of local alignment kernel based method are 89.7% and 92.68%,
      respectively. The accuracy and specificity of PseAAC-based method are 83.82% and
      85.36%, respectively. By computational analysis, out of 22 peptides of p24
      protein, 4 peptides are anticancer and 18 are non-anticancer. In the Ames test
      results, it is clear that anticancer peptides (ARP788.8 and ARP788.21) are not
      mutagenic. Therefore the results demonstrate that the described computation
      methods are useful to identify potential anticancer peptides, which are worthy of
      further experimental validation and 2 peptides (ARP788.8 and ARP788.21) of HIV-1
      p24 protein can be used as new anticancer candidates without mutagenicity. 

PMID- 24035843
TI  - Dissolved organic carbon and trihalomethane precursor removal at a UK upland
      water treatment works.
AB  - The removal of dissolved organic carbon (DOC) during potable water treatment is
      important for maintaining aesthetic water quality standards, minimising
      concentrations of micro-pollutants, controlling bacterial regrowth within
      distribution systems and, crucially, because it contains a sub-component that can
      act as trihalomethane (THM) precursors. In this study, the concentration and
      characteristics of raw water DOC and THM formation potential (THMFP) entering an
      upland potable water treatment works were analysed over twelve months.
      Correlations between raw water DOC characteristics, standardised THMFP (STHMFP)
      and % DOC removal were also investigated. DOC and THM precursor removal during a
      series of treatment stages was examined over this period, as well as potential
      selectivity in the removal of DOC fractions, to assess the importance of
      different treatment stages for DOC removal and THM amelioration. Though THMFP
      removal remained high and fairly stable throughout the study period (83-89%), the
      data suggest that this was mostly the result of high DOC removal rates rather
      than the selective removal of THM precursors. Whilst this chemical agnosticism
      makes DOC removal more robust, it may make the overall process more vulnerable to
      exceeding permissible THM concentrations under changing climatic conditions. The
      kinetics of the reaction between DOC and chlorine appeared to vary seasonally,
      indicating temporal changes in the proportions of fast- and slow-reacting
      precursors with implications for THM concentrations at the point of delivery to
      the consumer. The initial treatment stages, comprising coagulation-flocculation
      and dissolved air floatation (DAF) were by far the most important in terms of
      bulk DOC removal and the preferential removal of THM precursors, though,
      surprisingly, DOC quality was also modified following chlorination and secondary
      rapid gravity filtration (RGF). Though net THM concentration decreased following
      initial treatment stages, a doubling in the proportion of brominated THMs
      (BrTHMs), which are reported to be more carcinogenic, was also observed. 

PMID- 24035844
TI  - Chemical interaction of atmospheric mineral dust-derived nanoparticles with
      natural seawater--EPS and sunlight-mediated changes.
AB  - Laboratory studies were conducted to investigate the interactions of
      nanoparticles (NPs) formed via simulated cloud processing of mineral dust with
      seawater under environmentally relevant conditions. The effect of sunlight and
      the presence of exopolymeric substances (EPS) were assessed on the: (1) colloidal
      stability of the nanoparticle aggregates (i.e. size distribution, zeta potential,
      polydispersity); (2) micromorphology and (3) Fe dissolution from particles. We
      have demonstrated that: (i) synthetic nano-ferrihydrite has distinct aggregation
      behaviour from NPs formed from mineral dusts in that the average hydrodynamic
      diameter remained unaltered upon dispersion in seawater (~1500 nm), whilst all
      dust derived NPs increased about three fold in aggregate size; (ii) relatively
      stable and monodisperse aggregates of NPs formed during simulated cloud
      processing of mineral dust become more polydisperse and unstable in contact with
      seawater; (iii) EPS forms stable aggregates with both the ferrihydrite and the
      dust derived NPs whose hydrodynamic diameter remains unchanged in seawater over
      24h; (iv) dissolved Fe concentration from NPs, measured here as <3 kDa filter
      fraction, is consistently >30% higher in seawater in the presence of EPS and the
      effect is even more pronounced in the absence of light; (v) micromorphology of
      nanoparticles from mineral dusts closely resemble that of synthetic ferrihydrite
      in MQ water, but in seawater with EPS they form less compact aggregates, highly
      variable in size, possibly due to EPS-mediated steric and electrostatic
      interactions. The larger scale implications on real systems of the EPS
      solubilising effect on Fe and other metals with the additional enhancement of
      colloidal stability of the resulting aggregates are discussed.

PMID- 24035845
TI  - Characterisation factors for life cycle impact assessment of sound emissions.
AB  - Noise is a serious stressor affecting the health of millions of citizens. It has
      been suggested that disturbance by noise is responsible for a substantial part of
      the damage to human health. However, no recommended approach to address noise
      impacts was proposed by the handbook for life cycle assessment (LCA) of the
      European Commission, nor are characterisation factors (CFs) and appropriate
      inventory data available in commonly used databases. This contribution provides
      CFs to allow for the quantification of noise impacts on human health in the LCA
      framework. Noise propagation standards and international reports on acoustics and
      noise impacts were used to define the model parameters. Spatial data was used to
      calculate spatially-defined CFs in the form of 10-by-10-km maps. The results of
      this analysis were combined with data from the literature to select input data
      for representative archetypal situations of emission (e.g. urban day with a
      frequency of 63 Hz, rural night at 8000 Hz, etc.). A total of 32 spatial and 216
      archetypal CFs were produced to evaluate noise impacts at a European level (i.e.
      EU27). The possibility of a user-defined characterisation factor was added to
      support the possibility of portraying the situation of full availability of
      information, as well as a highly-localised impact analysis. A Monte Carlo-based
      quantitative global sensitivity analysis method was applied to evaluate the
      importance of the input factors in determining the variance of the output. The
      factors produced are ready to be implemented in the available LCA databases and
      software. The spatial approach and archetypal approach may be combined and
      selected according to the amount of information available and the life cycle
      under study. The framework proposed and used for calculations is flexible enough
      to be expanded to account for impacts on target subjects other than humans and to
      continents other than Europe.

PMID- 24035846
TI  - Modulation of EGFR and ROS induced cytochrome c release by combination of
      photodynamic therapy and carboplatin in human cultured head and neck cancer cells
      and tumor xenograft in nude mice.
AB  - Photodynamic therapy in combination with different treatment modalities has been
      evaluated to study the mechanism of cellular cytotoxicity and apoptosis in
      various forms of cancer. In the present study, human head and neck cancer cells
      were treated with radachlorin mediated photodynamic therapy and the chemotherapy
      drug, carboplatin singly or in combination. Several parameters were studied to
      check the enhanced cytotoxicity of combination therapy at different time
      interval. From the cell viability study by MTT assay, a 22% decrease in cell
      viability was observed in combination treatment. This enhanced activity of
      combination treatment was confirmed by cell migration assay and Hoechst PI
      staining. Generation of reactive oxygen species was observed and found to be
      higher than that of individual treatments. Cytochrome c was found to be released
      from mitochondria that also induced the enhance efficacy in combination
      treatment. The expression of other proteins like EGFR and PARP was also modulated
      with the time of incubation after treatment. In the tumor xenograft study in nude
      mouse model, the carboplatin treated group did not show any noticeable changes in
      tumor volume whereas tumor volume was reduced in PDT and the combination group.
      Though the difference in the reduction of the tumor size was not significant
      between PDT and combination group, there was a difference in the expression of
      EGFR between these two groups. Histologic study of the inhibition in tumor growth
      was also performed. Therefore, this study may provide an avenue of combating head
      and neck cancer by a combination of conventional chemotherapy and PDT. 

PMID- 24035847
TI  - Antibacterial and antifungal activity of photoactivated ZnO nanoparticles in
      suspension.
AB  - Antibacterial activity of photoactivated zinc oxide nanoparticles (ZnO NPs)
      against human pathogens Escherichia coli O157:H7, Listeria monocytogenes ATCL3C
      7644 and plant pathogen Botrytis cinerea was investigated. Data indicate that
      photoactivated (lambda = 400 nm) ZnO NPs at concentration 1 * 10(-3)M and
      incubation time 60 min reduced population of both bacteria by 7 log (CFU/ml).
      Clear dependence of antimicrobial properties of ZnO NPs on used concentration and
      incubation time was found. Scanning electron microscopy (SEM) images of treated
      bacteria indicate that treatment induced cell wall disintegration and lysis.
      Results obtained on examination of antifungal activity of ZnO NPs reveal that
      significant photoinactivation (58%) of B. cinerea was observed at NPs
      concentration 5 * 10(-3)M and incubation time of 24h. SEM analysis confirmed that
      substantial morphological changes occur in the microfungus after treatment. The
      data suggest that ZnO NPs in the presence of visible light exhibit strong
      antibacterial and antifungal activity. Such ZnO NPs properties obviously could be
      used for the development of effective fungicides in agriculture or innovative
      physical antibacterial agents, so important in medicine and food microbial
      control.

PMID- 24035848
TI  - Gastroprotective activity of Cenostigma macrophyllum Tul. var. acuminata Teles
      Freire leaves on experimental ulcer models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cenostigma macrophyllum Tul. var. acuminata Teles
      Freire (Leguminosae-Caesalpinioideae), popularly known in Brazil as "caneleiro",
      is widely used in folk medicine against gastrointestinal diseases. In previous
      studies, the ethanol extract of leaves from Cenostigma macrophyllum Tul. var.
      acuminata Teles Freire had shown antinociceptive, anti-inflammatory,
      antibacterial, antioxidant and antiulcerogenic activities. AIM OF THE STUDY: The
      aim of this study was to assess the gastroprotective effect of the hydroalcoholic
      fraction of leaves of Cenostigma macrophyllum Tul. var. acuminata Teles Freire
      (Cm-FHA), as well as to elucidate the possible underlying mechanisms of action.
      MATERIALS AND METHODS: Mice were used for the evaluation of the acute toxicity,
      and mice and rats to study the gastroprotective activity. The potential
      gastroprotective of Cm-FHA was assessed on different gastric ulcer models in
      rodents, such as absolute ethanol, HCl/ethanol, ischemia-reperfusion, cold
      restraint stress and indomethacin. The participation of prostaglandins, NO
      synthase pathway and ATP-sensitive potassium channels (KATP) in gastroprotective
      activity of Cm-FHA were evaluated after treatment with a cyclooxygenase inhibitor
      (indomethacin), a NO-synthase inhibitor (L-NAME) and a KATP channel blocker
      (glibenclamide 5mg/kg), respectively. Likewise, the catalase activity was
      determinated in order to assess the possible participation of antioxidant
      mechanisms. RESULTS: No signs of acute toxicity was observed after oral acute
      administration of Cm-FHA, considering the analyzed parameters. Likewise, Cm-FHA
      promoted a protective effect against gastric ulcers induced by absolute ethanol
      (lesion inhibition by 40% at both 100 and 200mg/kg), HCl/ethanol (lesion
      inhibition by 50 or 48% at 100 or 200mg/kg, respectively), ischemia-reperfusion
      (lesion inhibition by 49 or 90% at 100 or 200mg/kg, respectively) and cold
      restraint stress (lesion inhibition by 63 or 76% at 100 or 200mg/kg,
      respectively), as well as a increase of catalase activity was observed.
      Otherwise, Cm-FHA was not able to protect gastric mucosa against indomethacin
      induced lesions. Nitric oxide release, the of KATP channels opening and
      antioxidant activity are the possibly involved in the Cm-FHA-induced
      gastroprotective activity. CONCLUSION: This study corroborates the folk medicine
      use of Cenostigma macrophyllum for treatment of gastric ulcers, as well as
      reinforces this species as a valuable source of promising natural drugs with
      gastroprotective activity.

PMID- 24035849
TI  - Persistence and reappearance of high-risk human papillomavirus after conization.
AB  - OBJECTIVE: Women with early cervical cancer or intraepithelial neoplasia grades 2
      and 3 (CIN2+) are treated by conization; however, they still have a higher risk
      for subsequent CIN2+ than the general female population. Persistence of high-risk
      (HR) human papillomavirus (HPV) is a key factor in the development of CIN2+. We
      investigated persistence and reappearance of type-specific HR HPV infection after
      conization and evaluated possible co-factors. METHODS: During 2002-2006, cervical
      swabs from 604 women were collected before conization, at 4-6 months and at 8-12
      months after conization. HPV was detected by HC2 and genotyped by LiPAv2.
      Information on co-factors was collected through a questionnaire. Associations
      were assessed by multivariate logistic regression analysis. RESULTS: HR HPV
      persistence rate was 9.5%. The alpha5/6 species were more likely to persist than
      alpha9 species (OR, 2.28; 95% CI, 1.11-4.70). For single infections, a doubling
      in viral load at enrolment increased the risk for persistence by 36% (95% CI,
      1.13-1.63). In addition, margin status was associated with risk of persistence.
      Smoking, oral contraceptive use and severity of the cervical lesion did not
      significantly affect persistence. Among the HPV infections that had cleared, 2.2%
      reappeared. CONCLUSION: Our study indicates that viral load is important in
      predicting HPV persistence. The alpha5/6 species were most likely to persist.
      However, most of these HPV types have a lower carcinogenic potential than the
      alpha7/alpha9 species and may be by-standers. Further studies are needed to
      assess whether pre-conization viral load can also predict subsequent CIN2+.

PMID- 24035850
TI  - Commentary on "Profiling serologic biomarkers in cirrhotic patients via high
      throughput Fourier transform infrared spectroscopy: toward a new diagnostic tool
      of hepatocellular carcinoma".

PMID- 24035851
TI  - Label free sensing platform for amyloid fibrils effect on living cells.
AB  - This study presents a multiparametric label-free analysis gathering surface
      plasmon resonance (SPR) and electrical impedance spectroscopy (EIS) for
      monitoring the progress of a model epithelial cell culture (Madin Darbey Canine
      Kidney - MDCK) exposed to a peptide with high bio-medical relevance, amyloid beta
      (Abeta42). The approach surpasses the limitations in using the SPR angle for
      analyzing confluent cell monolayers and proposes a novel quantitative analysis of
      the SPR dip combined with advanced EIS as a tool for dynamic cell assessment.
      Long, up to 48h time series of EIS and SPR data reveal a biphasic cellular
      response upon Abeta42 exposure corresponding to changes in cell-substrate
      adherence, cell-cell tightening or cytoskeletal remodeling. The equivalent
      circuit used for fitting the EIS spectra provided substantiation of SPR analysis
      on the progress of cell adhesion as well as insight on dynamics of cell-cell
      junction. Complementary endpoint assays: western blot analysis and atomic force
      microscopy experiments have been performed for validation. The proposed label
      free sensing of nonlethal effect of model amyloid protein at cellular level
      provides enhanced resolution on cell-surface and cell-cell interactions modulated
      by membrane related protein apparatus, applicable as well to other adherent cell
      types and amyloid compounds. 

PMID- 24035852
TI  - Electrochemical immunosensor for the determination of insulin-like growth factor
      1 using electrodes modified with carbon nanotubes-poly(pyrrole propionic acid)
      hybrids.
AB  - An amperometric immunosensor for the determination of the hormone insulin-like
      growth factor 1 (IGF1) is reported for the first time in this work. As
      electrochemical transducer, a multiwalled carbon nanotubes-modified glassy carbon
      electrode on which poly(pyrrole propionic acid) was electropolymerized was
      prepared. This approach provided a high content of surface confined carboxyl
      groups suitable for direct covalent binding of anti-IGF1 monoclonal antibody. A
      sandwich-type immunoassay using a polyclonal antibody labeled with peroxidase,
      hydrogen peroxide as the enzyme substrate and catechol as redox mediator was
      employed to monitor the affinity reaction. All the variables involved in the
      preparation of the modified electrode were optimized and the electrodes were
      characterized by electrochemical impedance spectroscopy and cyclic voltammetry.
      Moreover, the different experimental variables affecting the amperometric
      response of the immunosensor were also optimized. The calibration graph for IGF1
      showed a range of linearity extending from 0.5 to 1000 pg/mL, with a detection
      limit, 0.25 pg/mL, more than 100 times lower than the lowest values reported for
      the ELISA immunoassays available for IGF1 (30 pg/mL, approximately). Excellent
      reproducibility for the measurements carried out with different immunosensors and
      selectivity against other hormones were also evidenced. A commercial human serum
      spiked with IGF1 at different levels between 0.01 and 10.0 ng/mL was analyzed
      with good results.

PMID- 24035853
TI  - Facile fabrication of network film electrodes with ultrathin Au nanowires for
      nonenzymatic glucose sensing and glucose/O2 fuel cell.
AB  - We report here on the facile fabrication of network film electrodes with
      ultrathin Au nanowires (AuNWs) and their electrochemical applications for high
      performance nonenzymatic glucose sensing and glucose/O2 fuel cell under
      physiological conditions (pH 7.4, containing 0.15M Cl(-)). AuNWs with an average
      diameter of ~7 or 2 nm were prepared and can self-assemble into robust network
      films on common electrodes. The network film electrode fabricated with 2-nm AuNWs
      exhibits high sensitivity (56.0 MUA cm(-2)mM(-1)), low detection limit (20 MUM),
      short response time (within 10s), excellent selectivity, and good storage
      stability for nonenzymatic glucose sensing. Glucose/O2 fuel cells were
      constructed using network film electrodes as the anode and commercial Pt/C
      catalyst modified glassy carbon electrode as cathode. The glucose/O2 fuel cell
      using 2-nm AuNWs as anode catalyst output a maximum power density of is 126 MUW
      cm(-2), an open-circuit cell voltage of 0.425 V, and a short-circuit current
      density of 1.34 mA cm(-2), respectively. Due to the higher specific electroactive
      surface area of 2-nm AuNWs, the network film electrode fabricated with 2-nm AuNWs
      exhibited higher electrocatalytic activity toward glucose oxidation than the
      network film electrode fabricated with 7-nm AuNWs. The network film electrode
      exhibits high electrocatalytic activity toward glucose oxidation under
      physiological conditions, which is helpful for constructing implantable
      electronic devices.

PMID- 24035854
TI  - Highly electrostatically-induced detection selectivity and sensitivity for a
      colloidal biosensor made of chitosan nanoparticle decorated with a few bare
      surfaced gold nanorods.
AB  - Metallic nanoparticles have been utilized as an analytical tool to detecting a
      wide variety of organic analytes. Among them, gold nanoparticles demonstrating
      outstanding surface plasmonic resonance property have been well recognized and
      received wide attention for plasmon-based sensing applications. However, in
      literature, gold-based nanosensor has to be integrated with specific "ligand"
      molecule in order to gain molecular recognition ability. However, "ligand"
      molecules, included proteins, peptides, nucleic acids, etc. are expensive and
      vulnerable to environmental change, in the meantime, anchoring procedure of the
      "ligand" molecules to gold surface may be cost-ineffective and endangered to the
      ligand's activity, making a final analytic probe less reliable and risk in
      production capability. Here, we develop a new approach by designing a colloid
      type sensor using a few "bare" Au nanorods deposited on the surface of a
      colloidal chitosan carrier. By tuning the solution pH, the resulting colloidal
      nanoprobe is capable of detecting proteins, i.e., human serum albumin and
      lysozyme, with high specificity and sensitivity. This new approach allows a new
      type of the molecular probes to be well manipulated to monitor important
      biomolecules for medical detection, diagnosis, and bioengineering applications. 

PMID- 24035855
TI  - Assaying multiple restriction endonucleases functionalities and inhibitions on
      DNA microarray with multifunctional gold nanoparticle probes.
AB  - Herein, a double-stranded (ds) DNA microarray-based resonance light scattering
      (RLS) assay with multifunctional gold nanoparticle (GNP) probes has been
      developed for studying restriction endonuclease functionality and inhibition.
      Because of decreasing significantly melting temperature, the enzyme-cleaved
      dsDNAs easily unwind to form single-stranded (ss) DNAs. The ssDNAs are hybridized
      with multiplex complementary ssDNAs functionalized GNP probes followed by silver
      enhancement and RLS detection. Three restriction endonucleases (EcoRI, BamHI and
      EcoRV) and three potential inhibitors (doxorubicin hydrochloride (DOX), ethidium
      bromide (EB) and an EcoRI-derived helical peptide (alpha4)) were selected to
      demonstrate capability of the assay. Enzyme activities of restriction
      endonucleases are detected simultaneously with high specificity down to the
      limits of 2.0 * 10(-2)U/mL for EcoRI, 1.1 * 10(-2)U/mL for BamHI and 1.6 * 10(
      2)U/mL for EcoRV, respectively. More importantly, the inhibitory potencies of
      three inhibitors are showed quantitatively, indicating that our approach has
      great promise for high-throughput screening of restriction endonuclease
      inhibitors.

PMID- 24035856
TI  - DNA-templated silver nanoclusters based label-free fluorescent molecular beacon
      for the detection of adenosine deaminase.
AB  - A general and reliable fluorescent molecular beacon is proposed in this work
      utilizing DNA-templated silver nanoclusters (AgNCs). The fluorescent molecular
      beacon has been employed for sensitive determination of the concentration of
      adenosine deaminase (ADA) and its inhibition. A well-designed oligonucleotide
      containing three functional regions (an aptamer region for adenosine assembly, a
      sequence complementary to the region of the adenosine aptamer, and an inserted
      six bases cytosine-loop) is adopted as the core element in the strategy. The
      enzymatic reaction of adenosine catalyzed by ADA plays a key role as well in the
      regulation of the synthesis of the DNA-templated AgNCs, i.e. the signal
      indicator. The intensity of the fluorescence signal may thereby determine the
      concentration of the enzyme and its inhibitor. The detection limit of the ADA can
      be lowered to 0.05 UL(-1). Also, 100 fM of a known inhibitor erythro-9-(2-hydroxy
      3-nonyl) adenine hydrochloride (EHNA) is enough to present distinguishable
      fluorescence emission. Moreover, since the fluorescent signal indicator is not
      required to be bound with the oligonucleotide, this fluorescent molecular beacon
      may integrate the advantages of both the label-free and signal-on strategies.

PMID- 24035857
TI  - Sub-femtomole detection of 16s rRNA from Legionella pneumophila using surface
      plasmon resonance imaging.
AB  - Legionellosis has been and continues to be a life-threatening disease worldwide,
      even in developed countries. Given the severity and unpredictability of
      Legionellosis outbreaks, developing a rapid, highly specific, and sensitive
      detection method is thus of great pertinence. In this paper, we demonstrate that
      sub-femtomole levels of 16s rRNA from pathogenic Legionella pneumophila can be
      timely and effectively detected using an appropriate designed capture, detector
      probes, and a QD SPRi signal amplification strategy. To achieve specific and
      sensitive detection, optimal hybridization conditions and parameters were
      implemented. Among these parameters, fragmentation of the 16s rRNA and further
      signal amplification by QDs were found to be the main parameters contributing to
      signal enhancement. The appropriate design of the detector probes also increased
      the sensitivity of the detection system, mainly due to secondary structure of 16s
      rRNA. The use of 16s rRNA from L. pneumophila allowed for the detection of
      metabolically active pathogens with high sensitivity. Detection of 16s rRNA in
      solutions as diluted as 1 pM at 450 MUL (0.45 femtomole) was achieved in less
      than 3h, making our approach suitable for the direct, timely, and effective
      detection of L. pneumophila within man-made water systems.

PMID- 24035858
TI  - A novel bioelectrochemical sensing platform based on covalently attachment of
      cobalt phthalocyanine to graphene oxide.
AB  - Graphene oxide-cobalt phthalocyanine (GO-PcCo) hybrid material as a new
      electrocatalyst was synthesized and used successfully to fabrication of new
      biosensor for the electrooxidation of l-cysteine (CSH) in aqueous media. Fourier
      transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS),
      thermogravimetric analysis (TGA), and transmission electron microscopy (TEM)
      images revealed that cobalt phthalocyanine is covalently attachment on graphene
      oxide sheets as single layers GO-PcCo. Cyclic voltammetric studies showed that
      the GO-PcCo/glassy carbon electrode (GO-PcCo/GCE) improves electrochemical
      behavior of CSH oxidation, as compared to the GO and PcCo. In addition, the
      results indicated that GO and PcCo have a synergic effect in the electrooxidation
      of CSH. The catalytic oxidation responses were studied and the reaction
      mechanisms were discussed. The electrocatalytic behavior is further developed as
      a new detection scheme for CSH by chronoamperometry method and under optimized
      conditions, excellent analytical features, including high sensitivity and
      selectivity, low detection limit and satisfactory dynamic range, were achieved. 

PMID- 24035859
TI  - Direct electron transfer of glucose oxidase and biosensing for glucose based on
      PDDA-capped gold nanoparticle modified graphene/multi-walled carbon nanotubes
      electrode.
AB  - In this work, poly (diallyldimethylammonium chloride) (PDDA)-capped gold
      nanoparticles (AuNPs) functionalized graphene (G)/multi-walled carbon nanotubes
      (MWCNTs) nanocomposites were fabricated. Based on the electrostatic attraction,
      the G/MWCNTs hybrid material can be decorated with AuNPs uniformly and densely.
      The new hierarchical nanostructure can provide a larger surface area and a more
      favorable microenvironment for electron transfer. The AuNPs/G/MWCNTs
      nanocomposite was used as a novel immobilization platform for glucose oxidase
      (GOD). Direct electron transfer (DET) was achieved between GOD and the electrode.
      Field emission scanning electron microscopy (FESEM), UV-vis spectroscopy and
      cyclic voltammetry (CV) were used to characterize the electrochemical biosensor.
      The glucose biosensor fabricated based on GOD electrode modified with
      AuNPs/G/MWCNTs demonstrated satisfactory analytical performance with high
      sensitivity (29.72mAM(-1)cm(-2)) and low limit of detection (4.8 uM). The
      heterogeneous electron transfer rate constant (KappaS) and the apparent Michaelis
      Menten constant (Km) of GOD were calculated to be 11.18s(-1) and 2.09 mM,
      respectively. With satisfactory selectivity, reproducibility, and stability, the
      nanostructure we proposed offered an alternative for electrode fabricating and
      glucose biosensing.

PMID- 24035860
TI  - Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of
      glucocorticoids in vitro.
AB  - Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However,
      they cause severe and irreversible side effects, which limit the use of these
      compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and
      anti-cancer effects. The present study was designed to investigate whether Rg1
      exhibits synergistic anti-inflammatory effects when combined with
      glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic
      RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then
      nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha) and glucocorticoid
      receptor (GR) expression were measured. The results showed that Rg1 or Cort could
      reduce the production of NO and TNF-alpha, and Rg1 dose-dependently up-regulated
      GR expression, while Cort dose-dependently down-regulated GR expression. The
      combination of low concentrations of Rg1 with Cort, which alone could not
      markedly inhibit the release of inflammatory factors, inhibited the secretion of
      NO and TNF-alpha in LPS-stimulated RAW264.7 macrophage cells, and up-regulated
      the expression of GR. The findings suggested Rg1 can synergize with
      glucocorticoid to enhance its anti-inflammatory effect. 

PMID- 24035861
TI  - Bayesian process-identification in bacteria transport in porous media.
AB  - A Bayesian parameter estimation approach is developed for the estimation of joint
      probability distribution functions for colloid and bacterial fate and transport
      model parameters describing breakthrough curves (BTCs) obtained through porous
      media column studies, and is applied to data involving different ionic strength
      solutions to fit models of differing complexity. Our approach focuses on the
      simultaneous fitting of a number of BTCs representing different conditions, and
      it provides a measure of the goodness of model structure, namely Deviance
      Information Criteria (DIC). Comparison of DIC per model fit enables the
      evaluation of the significance of various processes through step-wise increases
      in complexity due to the addition of process model components. We use the method
      to investigate the transport of both flagellated and non-flagellated strains of
      Azotobacter vinelandii in a simulated porous media under three ionic strengths.
      Three different model structures are considered: one without a detachment process
      and with Langmuirian blocking function, one with detachment, and one with
      detachment and a second-order blocking function based on random sequential
      adsorption. First, the model was applied separately to each single BTC. Next, the
      model was applied comprehensively to the experiments under various ionic
      strengths, whereas some transport parameters including dispersivity, detachment
      coefficient, the fraction of cells undergoing irreversible attachment, and the
      coefficient of the second-order blocking term were assumed to be the same under
      different ionic strengths. In most cases, including detachment substantially
      improved the DIC as expected, whereas using the second-order blocking improved
      DIC for most of the cases when the method was applied to separate BTCs but not
      when the method was applied collectively to the three BTCs obtained under various
      ionic strengths. Also, comparing the outcomes of the separate applications of the
      parameter estimation algorithm versus the collective application indicates that
      the uncertainty associated with the estimated parameters is substantially smaller
      when the collective approach is used and also that the estimated parameters are
      more consistent with the expectations based on the underlying physical processes.

PMID- 24035862
TI  - Brain-derived neurotrophic factor G196A polymorphism predicts 90-day outcome of
      ischemic stroke in Chinese: a novel finding.
AB  - BACKGROUND AND PURPOSE: Recovery after stroke varies considerably between
      individuals. An abundance of evidence suggests that genetic factors contribute to
      stroke recovery. The aim of this study was to determine whether or not the BDNF
      G196A polymorphism independently influences the occurrence, severity, and 90-day
      functional outcome in Chinese patients with ischemic stroke (IS). METHODS: BDNF
      G196A genetic variants were investigated in 494 IS and 346 controls. Severity was
      assessed by the National Institutes of Health Stroke Scale at the time of
      admission. Three hundred and eight patients were assessed 90 days post-stroke
      using the Modified Rankin Scale to determine stroke outcome. RESULTS: We showed
      that a significant association existed between the BDNF G196A AA genotype and the
      occurrence of IS (P=0.021), even after adjustment for covariates (P=0.028). The
      AA genotype of the BDNF G196A was associated with a poor outcome of recovery 3
      months after stroke onset (P=0.008) was a novel finding, independent of other
      known predictors of poor outcome (P=0.012). CONCLUSIONS: The BDNF G196A
      polymorphism was significantly associated with the occurrence and long-term
      outcomes of IS, thus BDNF G196A may be used as a prognostic biomarker and
      therapeutic target in IS.

PMID- 24035863
TI  - Cardioprotection of 17beta-estradiol against hypoxia/reoxygenation in
      cardiomyocytes is partly through up-regulation of CRH receptor type 2.
AB  - Estrogens have been suggested to exert cardioprotection through maintaining
      endogenous cardioprotective mechanisms. In the present study, we investigated
      whether estrogens protect cardiomyocytes against hypoxia/reoxygenation (H/R) via
      modulating urocortins (UCNs) and their receptor corticotrophin-releasing hormone
      receptor type 2 (CRHR2). We found that 17beta-estradiol (E2) enhanced UCN
      cardioprotection against H/R and increased CRHR2 expression in neonatal rat
      cardiomyocytes. E2 protected cardiomyocytes against H/R, which was impaired by
      CRHR2 antagonist or knockdown of CRHR2. Estrogen receptor alpha (ERalpha)
      antagonist treatment or ERalpha knockdown could abolish E2-induced CRHR2 up
      regulation. Moreover, knockdown of Sp1 also attenuated E2-induced CRHR2 up
      regulation. Ovariectomy resulted in down-regulation of CRHR2 and Sp-1 in
      myocardium of mice, which was restored by E2 or ERalpha agonist treatment. These
      results suggest that estrogens act on ERalpha to up-regulate CRHR2 expression in
      cardiomyocytes, thereby enhancing cardioprotection of UCNs against H/R. 

PMID- 24035865
TI  - Translational control of gene expression in the gonadotrope.
AB  - The study of gene expression in gonadotropes has largely focused on the variety
      of mechanisms regulating transcription of the gonadotropin genes and ancillary
      factors that contribute to the overall phenotype and function of these cells in
      reproduction. However, there are aspects of the response to GNRH signaling that
      are not readily explained by changes at the level of transcription. As our
      understanding of regulation at the level of mRNA translation has increased, it
      has become evident that GNRH receptor signaling engages multiple aspects of
      translational regulation. This includes activation of cap-dependent translation
      initiation, translational pausing caused by the unfolded protein response and RNA
      binding protein interaction. Gonadotropin mRNAs and the mRNAs of other factors
      that control the transcriptional and signaling responses to GNRH have been
      identified as targets of regulation at the level of translation. In this review
      we examine the impact of translational control of the expression of gonadotropin
      genes and other genes relevant to GNRH-mediated control of gonadotrope function. 

PMID- 24035868
TI  - Malondialdehyde regulates glucose-stimulated insulin secretion in murine islets
      via TCF7L2-dependent Wnt signaling pathway.
AB  - Evidence showed strong relations between malondialdehyde (MDA) levels and
      different pathological stages of diabetes. Here, an explicit system with freshly
      isolated islets and precisely controlled MDA gradient was employed to investigate
      the physiological effect of MDA on GSIS. Promoter analysis, pathway mapping, Q
      PCR profiling, and siRNA verification were performed to clarify the intracellular
      signaling pathways. MDA at a moderately high level (5 and 10MUM) promoted GSIS
      and accompanied with ATP/ADP ratio, cytosolic Ca(2+) level, and key regulators
      (GK, GLUT2, PDX1, and UCP2) changes in islets. Both upstream (PI3K and p-AKT) and
      downstream (TCF7L2 and TCF7) factors of Wnt pathway showed greatest changes.
      Knockdown of TCF7L2 blocked the MDA-induced GSIS elevation. These results
      indicated that MDA acted as a signaling messenger and regulated islet GSIS mainly
      through Wnt pathway. Therefore, the elevated MDA level and up-regulated Wnt
      signaling pathway could be an etiological factor in the development of
      hyperinsulinemia and type 2 diabetes. 

PMID- 24035866
TI  - Genetic and epigenetic changes in sporadic endocrine tumors: parathyroid tumors.
AB  - Parathyroid neoplasia is most commonly due to benign parathyroid adenoma but
      rarely can be caused by malignant parathyroid carcinoma. Evidence suggests that
      parathyroid carcinomas rarely, if ever, evolve through an identifiable benign
      intermediate, with the notable exception of carcinomas associated with the
      familial hyperparathyroidism-jaw tumor syndrome. Several genes have been directly
      implicated in the pathogenesis of typical sporadic parathyroid adenoma; somatic
      mutations in the MEN1 tumor suppressor gene are the most frequent finding, and
      alterations in the cyclin D1/PRAD1 oncogene are also firmly established molecular
      drivers of sporadic adenomas. In addition, good evidence supports mutation in the
      CDKN1B/p27 cyclin-dependent kinase inhibitor (CDKI) gene, and in other CDKI genes
      as contributing to disease pathogenesis in this context. Somatic defects in
      additional genes, including beta-catenin, POT1 and EZH2 may contribute to
      parathyroid adenoma formation but, for most, their ability to drive parathyroid
      tumorigenesis remains to be demonstrated experimentally. Further, genetic
      predisposition to sporadic presentations of parathyroid adenoma appears be
      conferred by rare, and probably low-penetrance, germline variants in CDKI genes
      and, perhaps, in other genes such as CASR and AIP. The HRPT2 tumor suppressor
      gene is commonly mutated in parathyroid carcinoma. 

PMID- 24035869
TI  - Respiratory viral infections in infants with clinically suspected pertussis.
AB  - OBJECTIVE: to evaluate the frequency of respiratory viral infections in
      hospitalized infants with clinical suspicion of pertussis, and to analyze their
      characteristics at hospital admission and clinical outcomes. METHODS: a
      historical cohort study was performed in a reference service for pertussis, in
      which the research of respiratory viruses was also a routine for infants
      hospitalized with respiratory problems. All infants reported as suspected cases
      of pertussis were included. Tests for Bordetella pertussis (BP) (polymerase chain
      reaction/culture) and for respiratory viruses (RVs) (immunofluorescence) were
      performed. Patients who received macrolides before hospitalization were excluded.
      Clinical data were obtained from medical records. RESULTS: Among the 67 patients
      studied, BP tests were positive in 44%, and 26% were positive for RV. There was
      no etiological identification in 35%, and RV combined with BP was identified in
      5%. All patients had similar demographic characteristics. Cough followed by
      inspiratory stridor or cyanosis was a strong predictor of pertussis, as well as
      prominent leukocytosis and lymphocytosis. Rhinorrhea and dyspnea were more
      frequent in viral infections. Macrolides were discontinued in 40% of patients who
      tested positive for RV and negative for BP. CONCLUSION: the results suggest that
      viral infection can be present in hospitalized infants with clinical suspicion of
      pertussis, and etiological tests may enable a reduction in the use of macrolides
      in some cases. However, the etiological diagnosis of respiratory virus infection,
      by itself, does not exclude the possibility of infection with BP.

PMID- 24035867
TI  - Evaluation of growth hormone (GH) action in mice: discovery of GH receptor
      antagonists and clinical indications.
AB  - The discovery of a growth hormone receptor antagonist (GHA) was initially
      established via expression of mutated GH genes in transgenic mice. Following this
      discovery, development of the compound resulted in a drug termed pegvisomant,
      which has been approved for use in patients with acromegaly. Pegvisomant
      treatment in a dose dependent manner results in normalization of IGF-1 levels in
      most patients. Thus, it is a very efficacious and safe drug. Since the GH/IGF-1
      axis has been implicated in the progression of several types of cancers, many
      have suggested the use of pegvisomant as an anti-cancer therapeutic. In this
      manuscript, we will review the use of mouse strains that possess elevated or
      depressed levels of GH action for unraveling many of GH actions. Additionally, we
      will describe experiments in which the GHA was discovered, review results of
      pegvisomant's preclinical and clinical trials, and provide data suggesting
      pegvisomant's therapeutic value in selected types of cancer. 

PMID- 24035870
TI  - Epidemiological and genetic characteristics associated with the severity of acute
      viral bronchiolitis by respiratory syncytial virus.
AB  - OBJECTIVE: to assess the epidemiological and genetic factors associated with
      severity of acute viral bronchiolitis (AVB) by respiratory syncytial virus (RSV).
      DATA SOURCE: the key words "bronchiolitis", "risk factor", "genetics" and
      "respiratory syncytial virus", and all combinations among them were used to
      perform a search in the PubMed, SciELO, and Lilacs databases, of articles
      published after the year 2000 that included individuals younger than 2 years of
      age. DATA SYNTHESIS: a total of 1,259 articles were found, and their respective
      summaries were read. Of these, 81 were selected, which assessed risk factors for
      the severity of AVB, and were read in full; the 60 most relevant studies were
      included. The epidemiologic factors associated with AVB severity by RSV were
      prematurity, passive smoking, young age, lack of breastfeeding, chronic lung
      disease, congenital heart disease, male gender, ethnicity, viral coinfection, low
      weight at admission, maternal smoking during pregnancy, atopic dermatitis,
      mechanical ventilation in the neonatal period, maternal history of atopy and/or
      asthma during pregnancy, season of birth, low socioeconomic status, Down
      syndrome, environmental pollution, living at an altitude > 2,500 meters above sea
      level, and cesarean section birth. Conversely, some children with severe AVB did
      not present any of these risk factors. In this regard, recent studies have
      verified the influence of genetic factors on the severity of AVB by RSV.
      Polymorphisms of the TLRs, RANTES, JUN, IFNA5, NOS2, CX3CR1, ILs, and VDR genes
      have been shown to be associated with more severe evolution of AVB by RSV.
      CONCLUSION: the severity of AVB by RSV is a phenomenon that depends on the
      varying degrees of interaction among epidemiological, environmental, and genetic
      variables.

PMID- 24035864
TI  - Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary
      adenoma.
AB  - Human pituitary adenomas are the most common intracranial neoplasms.
      Approximately 5% of them are familial adenomas. Patients with familial tumors
      carry germline mutations in predisposition genes, including AIP, MEN1 and
      PRKAR1A. These mutations are extremely rare in sporadic pituitary adenomas, which
      therefore are caused by different mechanisms. Multiple tumor suppressive genes
      linked to sporadic tumors have been identified. Their inactivation is caused by
      epigenetic mechanisms, mainly promoter hypermethylation, and can be placed into
      two groups based on their functional interaction with tumor suppressors RB or
      p53. The RB group includes CDKN2A, CDKN2B, CDKN2C, RB1, BMP4, CDH1, CDH13,
      GADD45B and GADD45G; AIP and MEN1 genes also belong to this group. The p53 group
      includes MEG3, MGMT, PLAGL1, RASSF1, RASSF3 and SOCS1. We propose that the tumor
      suppression function of these genes is mainly mediated by the RB and p53
      pathways. We also discuss possible tumor suppression mechanisms for individual
      genes. 

PMID- 24035871
TI  - Temporal evolution of acute respiratory distress syndrome definitions.
AB  - OBJECTIVE: to review the evolution of acute respiratory distress syndrome (ARDS)
      definitions and present the current definition for the syndrome. DATA SOURCE: a
      literature review and selection of the most relevant articles on ARDS definitions
      was performed using the MEDLINE(r)/PubMed(r) Resource Guide database (last ten
      years), in addition to including the most important articles (classic articles)
      that described the disease evolution. DATA SYNTHESIS: the review included the
      following subjects: introduction; importance of definition; description of the
      first diagnostic criterion and subsequently used definitions, such as acute lung
      injury score; definition by the American-European Consensus Conference, and its
      limitations; description of the definition by Delphi, and its problems; accuracy
      of the aforementioned definitions; description of most recent definition (the
      Berlin definition), and its limitations; and practical importance of the new
      definition. CONCLUSIONS: ARDS is a serious disease that remains an ongoing
      diagnostic and therapeutic challenge. The evolution of definitions used to
      describe the disease shows that studies are needed to validate the current
      definition, especially in pediatrics, where the data are very scarce.

PMID- 24035872
TI  - Massage in children with cancer: effectiveness of a protocol.
AB  - OBJECTIVES: massage can help relieve pain, although empirical evidence is scarce
      and contradictory. This study aims to assess the effectiveness of a massage
      protocol in relieving pain in children hospitalized with cancer. METHODS: a
      randomized, controlled, and single-blind trial was performed in a sample of 52
      children aged between 10 and 18 years who were hospitalized in a pediatric cancer
      ward. The intervention consisted of the implementation of a massage protocol with
      three sessions of 20 to 30minutes on alternate days over a one-week period. The
      effectiveness of the protocol was evaluated by assessing pain using the Brief
      Pain Inventory (BPI), while the effectiveness of each massage session was
      measured using the Visual Analogue Scale (VAS). RESULTS: the massage protocol was
      only effective in reducing the interference of pain in walking (p<0.05), although
      it also contributed to relieve pain and its impact on the children's activities.
      After each massage session, the intensity of the pain experienced by the child
      decreased (p<0.001). CONCLUSIONS: despite the small sample size, massage therapy
      appears to be a useful intervention in reducing pain in children with cancer.
      However, there are still questions regarding the effectiveness of this massage
      protocol. The authors recommend its use due to its contribution to the promotion
      of the child's well-being and quality of life.

PMID- 24035873
TI  - Early cow's milk consumption among Brazilian children: results of a national
      survey.
AB  - OBJECTIVE: to assess the intake, frequency, and type of milk consumed by
      Brazilian children younger than 60 months of age. METHODS: this was a cross
      sectional study, which used secondary data from the National Demographic and
      Health Survey of 2006-2007. Data from 4,817 children under the age of 60 months
      were used. All analyses were performed with expanded samples. The dietetic survey
      assessed the previous day's consumption, and estimates were made through
      univariate analysis, presented as a percentage. RESULTS: on the day prior to the
      survey, breast milk was consumed by 91% of the children younger than six months
      of age, by 61.5% of the children aged 6 to 12 months, and by 34.8% of the
      children aged 13 to 24 months. Among the children who had received other types of
      milk, cow's milk was consumed by 62.4% of the children younger than six months,
      by 74.6% of the children aged 6 to 12 months, and by approximately 80% of the
      children older than 12 months. Infant formulas were consumed by 23% of the
      children younger than six months of age, by 9.8% of the children aged 6 to 12
      months, and by less than 1% of the older children. Soy milk consumption varied
      from 14.6% to 20% among the investigated ages. Non-breast milk consumption before
      the age of six months was more frequent in children living in the Northeastern
      and Southern regions. CONCLUSION: the results of the present study demonstrated
      that most children received cow's milk prematurely as a substitute for breast
      milk, highlighting the importance of the development of public policies to
      promote, protect, and support breastfeeding in all regions of Brazil, aiming at
      reversing the observed scenario.

PMID- 24035874
TI  - Predictive capacity of different bioelectrical impedance analysis devices, with
      and without protocol, in the evaluation of adolescents.
AB  - OBJECTIVE: this study was performed to determine the predictive capacity of four
      different bioelectrical impedance analysis (BIA) devices in the assessment of
      adolescents, with and without a protocol. METHODS: a cross-sectional study was
      performed with 215 adolescents aged 10 to 14 years, of both genders, evaluated
      through anthropometry and body composition by dual energy X-ray absorptiometry
      (DXA) and by four different BIA devices, with and without a protocol. The
      following tests were used: Kolmogorov-Smirnov's, chi-squared, Student's t or Mann
      Whitney's, Kruskal-Wallis's, Wilcoxon's, and kappa index. The ROC curves were
      constructed and the sensitivity, specificity, and positive and negative
      predictive values were calculated. RESULTS: of the 215 adolescents, 44.2% had
      excessive body fat. The tetrapolar BIA device equipped with eight tactile
      electrodes showed more sensitivity and results that were closer to those obtained
      by DXA (area under the ROC curve [AUC] = 0.964 with protocol and AUC = 0.973
      without protocol, p < 0.001), as well as greater agreement (k = 0.67 with
      protocol and k = 0.63 without protocol, p < 0.001). The evaluation without
      protocol was similar to that by DXA in most investigated situations (p > 0.05).
      CONCLUSION: BIA is capable of predicting alterations in adolescents' body
      composition. When it is impossible to perform the assessment with a protocol, its
      results may be useful in population studies.

PMID- 24035875
TI  - Factors associated with hookah use initiation among adolescents.
AB  - OBJECTIVE: to determine the prevalence and to analyze factors associated with
      hookah use initiation among adolescents. METHODS: This was a cross-sectional
      study, in which questionnaires were collected from 495 students attending public
      and private schools of the urban area of the city of Varzea Grande, in the state
      of Mato Grosso, Brazil. Data were analyzed through descriptive, bivariate, and
      multiple Poisson regression analyses. RESULTS: A total of 19.7% students had
      tried a hookah. The use of hookah was associated with the final period of
      adolescence [PR=6.54 (2.79, 15.32)]; enrollment in private schools [PR=2.23
      (1.73, 2.88)]; and presence of work activities [PR=1.80 (1.17, 2.78)].
      CONCLUSION: The proportion of adolescents that had tried a hookah was high. The
      influence of age, work activities, and class period on smoking initiation using
      the hookah was observed. Preventive measures encompassing all forms of tobacco
      smoking should be targeted at adolescents in the school environment, aiming at
      tobacco use control.

PMID- 24035876
TI  - Risk factors associated with wheezing in infants.
AB  - OBJECTIVE: to identify possible risk factors associated with wheezing in infants
      (12-15 months-old) in the state of Mato Grosso, Brazil. METHODS: this was a cross
      sectional study performed by applying a standardized written questionnaire from
      the international study on wheezing in infants (Estudio Internacional de
      Sibilancia en Lactantes - EISL), phase 3. Parents and/or guardians of infants
      were interviewed at primary health care clinics or at home from August of 2009 to
      November of 2010. Factors associated to wheezing were studied using bivariate and
      multivariate analysis (using the Statistical Package for Social Sciences [SPSS]
      v.18.0), and expressed as odds ratios (OR) and 95% confidence intervals (95% CI).
      RESULTS: the written questionnaire was answered by 1,060 parents and/or
      guardians. The risk factors for wheezing were: history of asthma in the family
      [mother (OR = 1.62; 95% CI = 1.07-2.43); father (OR = 1.98; 95% CI = 1.22-3.23);
      siblings (OR = 2.13; 95% CI = 1.18-3.87)]; history of previous pneumonia (OR =
      10.80; 95% CI = 4.52-25.77); having had more than six upper respiratory tract
      infections (URTIs) (OR = 2.95; 95% CI = 2.11-4.14); having had first URTI before
      the third month of life (OR = 1.50; 95% CI = 1.04-2.17); living in a moderately
      polluted area (OR = 1.59; 95% CI = 1.08-2.33); paracetamol use for URTI (OR =
      2.13; 95% CI = 1.54-2.95); and antibiotic use for skin infection (OR = 2.29; 95%
      CI = 1.18-4.46). CONCLUSIONS: the study of risk factors for wheezing in the first
      year of life is important to help physicians identify young children at high risk
      of developing asthma and to improve public health prevention strategies in order
      to reduce the morbidity of wheezing in childhood.

PMID- 24035877
TI  - Cow's milk allergy: color Doppler ultrasound findings in infants with
      hematochezia.
AB  - OBJECTIVE: ultrasound (US) has been an important diagnostic tool to identify
      several causes of gastrointestinal bleeding. Infants with cow's milk allergy
      (CMA) may present hematochezia and the confirmation of the diagnosis can be
      difficult. The aim of this study is to describe grayscale and color Doppler
      ultrasound findings in patients with CMA. METHODS: we retrospectively studied 13
      infants with CMA. All infants presented severe hematochezia and abdominal pain.
      All underwent an US study with the diagnosis of allergic colitis. This diagnosis
      was based on clinical findings, recovery after infant or mother exclusion diets
      in the case of exclusive breastfeeding and positive oral challenge test. RESULTS:
      the mean age ranged from 1 to 6 months (mean=3.53). Seven out of 13 infants
      (53.8%) had grayscale and color Doppler sonographic repeated after exclusion
      diet. Twelve out of 13 (92,3%) showed abnormalities at US and CDUS at beginning.
      The positive findings suggesting colitis were thickened bowel walls and increased
      vascularity, especially in the descending and sigmoid colon. Colonoscopy and
      histopathological findings were compatible with allergic colitis. After a diet
      change the 13 infants recovered and their oral challenge tests were positive.
      CONCLUSION: Doppler US may be very useful in diagnosing secondary colitis, such
      as CMA, and to exclude several other abdominal diseases that can emulate this
      disease.

PMID- 24035878
TI  - Effect of low-intensity treadmill exercise on behavioural measures and
      hippocampal parvalbumin immunoreactivity in the rat.
AB  - Exercise has been demonstrated to have positive effects on both the body and
      brain. The present study aimed to determine the behavioural and morphological
      consequence of low-intensity running. Rats were exercised on a treadmill for a
      total of 30 days, 30 min/day. Social interaction, locomotor activity and
      behaviour on an elevated plus maze were assessed post-treatment. Exercised
      animals demonstrated more passive interaction and less time not interacting than
      control animals that were not exercised. Conversely, locomotor and anxiety
      measures showed no effect of exercise. Analysis of brains demonstrated an
      increase in expression of parvalbumin immunoreactive neurons in the hippocampus
      localised to the CA1 and CA2/3 regions. These results demonstrate that low
      intensity exercise leads to changes in social behaviour as well as neuroplastic
      morphological changes within the hippocampus.

PMID- 24035879
TI  - Effect of head turns on the localization accuracy of sounds in the European
      starling (Sturnus vulgaris).
AB  - Long signal durations that represent closed-loop conditions permit responses
      based on the sensory feedback during the presentation of the stimulus, while
      short stimulus durations that represent open-loop conditions do not allow for
      directed head turns during signal presentation. A previous study showed that for
      broadband noise stimuli, the minimum audible angle (MAA) of the European starling
      (Sturnus vulgaris) is smaller under closed-loop compared to open-loop conditions
      (Feinkohl & Klump, 2013). Head turns represent a possible strategy to improve
      sound localization cues under closed-loop conditions. In this study, we analyze
      the influence of head turns on the starling MAA for broadband noise and 2 kHz
      tones under closed-loop and open-loop conditions. The starlings made more head
      turns under closed-loop conditions compared to open-loop conditions. Under closed
      loop conditions, their sensitivity for discriminating sound source positions was
      best if they turned their head once or more per stimulus presentation. We discuss
      potential cues generated from head turns under closed-loop conditions.

PMID- 24035880
TI  - Prediction of early and late complications after oral mucosal graft harvesting:
      multivariable analysis from a cohort of 553 consecutive patients.
AB  - PURPOSE: We investigated the early and late complications after oral mucosal
      graft harvesting, and reported the independent predictors of outcome via
      multivariable analysis. MATERIALS AND METHODS: We performed a retrospective
      descriptive study of 553 patients from whom an oral mucosa graft was harvested
      for urethroplasty from single or bilateral cheeks. Patients who underwent oral
      mucosa harvesting from the lip, the tongue or from the cheek and lip at the same
      time were excluded from analysis. The oral graft was harvested in an ovoid shape
      with closure of the wound. Postoperative early and late complications were
      investigated using a self-administered, nonvalidated, semiquantitative
      questionnaire. There were 6 questions on early complications, and 13 questions
      investigated late complications and patient satisfaction. RESULTS: Descriptive
      statistics of categorical variables focused on frequencies and proportions.
      Univariable and multivariable analyses were used to predict early and late
      dissatisfaction of patients. Bleeding was reported in 3.4% of patients. Overall
      53.2% of patients did not report any pain and 36.3% reported no swelling. Late
      complications analysis showed that 95.5% of patients declared that the surgical
      closure of the wound did not cause any difficulty in opening the mouth or
      problems with smiling (98.2%) and/or dry mouth (95.8%). Overall 98.2% of patients
      were satisfied with the procedure. Univariable and multivariable analyses
      revealed that bilateral graft harvesting was the only significant predictor of
      patient dissatisfaction (OR 2.85, p = 0.01 and OR 2.72, p = 0.02; respectively).
      CONCLUSIONS: Harvesting the oral mucosa ovoid graft from a single cheek with
      closure of the wound is a safe procedure with high rates of patient satisfaction.

PMID- 24035881
TI  - A tissue graft model of DNA damage response in the normal and malignant human
      prostate.
AB  - PURPOSE: DNA damage responses are relevant to prostate cancer initiation,
      progression and treatment. Few models of the normal and malignant human prostate
      that maintain stromal-epithelial interactions in vivo exist in which to study DNA
      damage responses. We evaluated the feasibility of maintaining tissue slice grafts
      at subcutaneous vs subrenal capsular sites in RAG2(-/-)gammaC(-/-) mice to study
      the DNA damage responses of normal and malignant glands. MATERIALS AND METHODS:
      We compared the take rate and histology of tissue slice grafts from fresh,
      precision cut surgical specimens that were maintained for 1 to 4 weeks in
      subcutaneous vs subrenal capsular sites. Induction of gammaH2AX, p53, ATM and
      apoptosis was evaluated as a measure of the DNA damage response after
      irradiation. RESULTS: The take rate of subcutaneous tissue slice grafts was
      higher than typically reported but lower than at the subrenal capsular site.
      Subcutaneous tissue slice grafts frequently showed basal cell hyperplasia,
      squamous metaplasia and cystic atrophy, and cancer did not survive. In contrast,
      normal and malignant histology was well maintained in subrenal capsular tissue
      slice grafts. Regardless of implantation site the induction of gammaH2AX and ATM
      occurred in tissue slice graft epithelium 1 hour after irradiation and decreased
      to basal level by 24 hours, indicating DNA damage recognition and repair. As
      observed previously in prostatic ex vivo models, p53 was not activated. Notably,
      tumor but not normal cells responded to irradiation by undergoing apoptosis.
      CONCLUSIONS: To our knowledge this is the first study of DNA damage responses in
      a patient derived prostate tissue graft model. The subrenal capsular site of
      RAG2(-/-)gammaC(-/-) mice optimally maintains normal and malignant histology and
      function, permitting novel studies of DNA damage responses in a physiological
      context.

PMID- 24035882
TI  - Loss of bacillus Calmette-Guerin viability adversely affects the direct response
      of urothelial carcinoma cells to bacillus Calmette-Guerin exposure.
AB  - PURPOSE: The attenuated mycobacterium bacillus Calmette-Guerin is widely used as
      intravesical immunotherapy for nonmuscle invasive urothelial carcinoma. Previous
      studies demonstrated that in the laboratory and clinical settings bacillus
      Calmette-Guerin viability is a variable that correlates with antitumor efficacy.
      We evaluated how loss of viability impacted a number of molecular and phenotypic
      intermediate end points that characterize and/or contribute to the direct effect
      of bacillus Calmette-Guerin on urothelial carcinoma cells. MATERIALS AND METHODS:
      We studied the effect of loss of bacillus Calmette-Guerin viability on the tumor
      cell response to the treatment in 2 human urothelial carcinoma cell lines. The
      cellular response to bacillus Calmette-Guerin rendered nonviable by heat killing
      was compared to the response to viable bacillus. Response end points included the
      induction of oxidative stress, activation of intracellular signaling pathways,
      gene transactivation and phenotypic changes. RESULTS: Loss of viability resulted
      in a quantitative decrease in the tumor cell response relative to that of viable
      bacillus Calmette-Guerin for all measured end points. The decrease in response
      varied by cell line, ranging from 15% to 100% of the response to viable bacillus.
      While responses were quantitatively different, nonviable bacillus continued to
      induce responses that were qualitatively similar to those of bacillus Calmette
      Guerin relative to that in untreated controls. CONCLUSIONS: Bacillus Calmette
      Guerin viability is an important variable influencing the direct tumor cell
      response to the treatment. Although the magnitude of its effects are attenuated,
      heat killed bacillus Calmette-Guerin remains active for the induction of bacillus
      Calmette-Guerin responsive biological end points.

PMID- 24035883
TI  - Expression of glycogen synthase (GYS) and glycogen synthase kinase 3beta
      (GSK3beta) of the Fujian oyster, Crassostrea angulata, in relation to glycogen
      content in gonad development.
AB  - To investigate the regulation of glycogen metabolism at the mRNA level in
      Crassostrea angulata, we cloned and characterized glycogen synthase and glycogen
      synthase kinase 3beta cDNAs (Ca-GYS and Ca-GSK3beta, respectively), which encode
      the primary enzymes involved in glycogen storage. We examined their expression
      profiles in different tissues and during different reproductive stages. The full
      length cDNA of GYS was 4771 bp in length with a 2023 bp open reading frame (ORF),
      predicted to encode a protein of 674 aa. The full-length GSK3beta cDNA was 2333
      bp long, with an ORF of 1242 bp. High expression levels of both genes were
      observed in the gonad and the adductor muscle, as compared to the mantle, gill,
      or visceral mass, which correlates well with the ability to store glucose. The
      regulation of both genes was correlated with glycogen content via qPCR and in
      situ hybridization and was dependent upon the stage of the reproductive cycle
      (initiation stage, maturation stage, ripeness stage). Thus, it appears that the
      expression of Ca-GYS and Ca-GSK3beta is driven by the reproductive cycle of the
      oyster, reflecting the central role played by glycogen in energy storage and
      gametogenic development in C. angulata. We suggest that Ca-GYS and Ca-GSK3beta
      can be used as useful molecular markers for identifying the stages of glycogen
      metabolism and reproduction in C. angulata.

PMID- 24035884
TI  - Impact of low-profile sheaths on vascular complications during transfemoral
      transcatheter aortic valve replacement.
AB  - AIMS: We sought to assess the impact of low-profile sheaths on vascular
      complications during transfemoral transcatheter aortic valve replacement (TAVR).
      METHODS AND RESULTS: This retrospective single-study population comprised a total
      of 375 consecutive patients with severe aortic stenosis who underwent
      transfemoral TAVR from January 2008 to November 2012. Of these, 204 (54.4%)
      underwent TAVR using 14-18 Fr sheaths (low-profile sheath [LPS] group), and 171
      (45.6%) using 19-24 Fr sheaths (high-profile sheath [HPS] group). Vascular
      complications and bleeding were defined according to the VARC-2 definitions.
      Lower-profile sheaths were associated with a lower incidence of major vascular
      complications (0.5% vs. 10.5%, p<0.001), as well as a lower rate of life
      threatening or major bleeding (3.4% vs. 8.3%, p=0.038). Finally, at multivariable
      analysis, sheath size >=19 Fr (adjusted odds ratio [OR]: 3.06, 95% confidence
      interval [CI]: 1.20-7.83; p=0.019) and a sheath external diameter/minimal femoral
      artery diameter ratio >=1.05 (adjusted OR: 5.79, 95% CI: 1.29-15.92, p=0.022)
      were found to be the only independent predictors of major and minor vascular
      complications. CONCLUSIONS: The introduction of lower-profile sheaths has
      dramatically reduced the incidence of vascular complications after transfemoral
      TAVR, thus enhancing the safety of the procedure.

PMID- 24035885
TI  - Schistosoma mansoni NAD(+) catabolizing enzyme: identification of key residues in
      catalysis.
AB  - Schistosoma mansoni NAD(+) catabolizing enzyme (SmNACE), a distant homolog of
      mammalian CD38, shows significant structural and functional analogy to the
      members of the CD38/ADP-ribosyl cyclase family. The hallmark of SmNACE is the
      lack of ADP-ribosyl cyclase activity that might be ascribed to subtle changes in
      its active site. To better characterize the residues of the active site we
      determined the kinetic parameters of nine mutants encompassing three acidic
      residues: (i) the putative catalytic residue Glu202 and (ii) two acidic residues
      within the 'signature' region (the conserved Glu124 and the downstream Asp133),
      (iii) Ser169, a strictly conserved polar residue and (iv) two aromatic residues
      (His103 and Trp165). We established the very important role of Glu202 and of the
      hydrophobic domains overwhelmingly in the efficiency of the nicotinamide-ribosyl
      bond cleavage step. We also demonstrated that in sharp contrast with mammalian
      CD38, the 'signature' Glu124 is as critical as Glu202 for catalysis by the
      parasite enzyme. The different environments of the two Glu residues in the
      crystal structure of CD38 and in the homology model of SmNACE could explain such
      functional discrepancies. Mutagenesis data and 3D structures also indicated the
      importance of aromatic residues, especially His103, in the stabilization of the
      reaction intermediate as well as in the selection of its conformation suitable
      for cyclization to cyclic ADP-ribose. Finally, we showed that inhibition of
      SmNACE by the natural product cyanidin requires the integrity of Glu202 and
      Glu124, but not of His103 and Trp165, hence suggesting different recognition
      modes for substrate and inhibitor. 

PMID- 24035886
TI  - Single and dual crosslinked oxidized methacrylated alginate/PEG hydrogels for
      bioadhesive applications.
AB  - A degradable, cytocompatible bioadhesive can facilitate surgical procedures and
      minimize patient pain and post-surgical complications. In this study a
      bioadhesive hydrogel system based on oxidized methacrylated alginate/8-arm
      poly(ethylene glycol) amine (OMA/PEG) has been developed, and the bioadhesive
      characteristics of the crosslinked OMA/PEG hydrogels evaluated. Here we
      demonstrate that the swelling behavior, degradation profiles, and storage moduli
      of crosslinked OMA/PEG hydrogels are tunable by varying the degree of alginate
      oxidation. The crosslinked OMA/PEG hydrogels exhibit cytocompatibility when
      cultured with human bone marrow-derived mesenchymal stem cells. In addition, the
      adhesion strength of these hydrogels, controllable by varying the alginate
      oxidation level and measured using a porcine skin model, is superior to
      commercially available fibrin glue. This OMA/PEG hydrogel system with
      controllable biodegradation and mechanical properties and adhesion strength may
      be a promising bioadhesive for clinical use in biomedical applications, such as
      drug delivery, wound closure and healing, biomedical device implantation, and
      tissue engineering. 

PMID- 24035887
TI  - Bioactive membranes for bone regeneration applications: effect of physical and
      biomolecular signals on mesenchymal stem cell behavior.
AB  - This study focuses on the in vitro characterization of bioactive elastin-like
      recombinamer (ELR) membranes for bone regeneration applications. Four bioactive
      ELRs exhibiting epitopes designed to promote mesenchymal stem cell adhesion
      (RGDS), endothelial cell adhesion (REDV), mineralization (HAP), and both cell
      adhesion and mineralization (HAP-RGDS) were synthesized using standard
      recombinant protein techniques. The materials were then used to fabricate ELR
      membranes incorporating a variety of topographical micropatterns including
      channels, holes and posts. Primary rat mesenchymal stem cells (rMSCs) were
      cultured on the different membranes and the effects of biomolecular and physical
      signals on cell adhesion, morphology, proliferation, and differentiation were
      evaluated. All results were analyzed using a custom-made MATLAB program for high
      throughput image analysis. Effects on cell morphology were mostly dependent on
      surface topography, while cell proliferation and cell differentiation were
      largely dependent on the biomolecular signaling from the ELR membranes. In
      particular, osteogenic differentiation (evaluated by staining for the
      osteoblastic marker osterix) was significantly enhanced on cells cultured on HAP
      membranes. Remarkably, cells growing on membranes containing the HAP sequence in
      non-osteogenic differentiation media exhibited significant up-regulation of the
      osteogenic marker as early as day 5, while those growing on fibronectin-coated
      glass in osteogenic differentiation media did not. These results are part of our
      ongoing effort to develop an optimized molecularly designed periosteal graft. 

PMID- 24035888
TI  - Effect of addition of hyaluronic acids on the osteoconductivity and
      biodegradability of synthetic octacalcium phosphate.
AB  - The present study was designed to investigate whether three sodium hyaluronic
      acid (HyA) medical products, Artz((r)), Suvenyl((r)) and a chemically modified
      derivative of sodium HyA Synvisc((r)), can be used as suitable vehicles for an
      osteoconductive octacalcium phosphate (OCP). OCP granules (300-500 MUm diameter)
      were mixed with these sodium HyAs with molecular weights of 90 * 10(4)
      (Artz((r))), 190 * 10(4) (Suvenyl((r))) and 600 * 10(4) (Synvisc((r))) (referred
      to as HyA90, HyA190 and HyA600, respectively). OCP-HyA composites were injected
      using a syringe into a polytetrafluoroethylene ring, placed on the subperiosteal
      region of mouse calvaria for 3 and 6 weeks, and then bone formation was assessed
      by histomorphometry. The capacity of the HyAs for osteoclast formation from
      RAW264 cells with RANKL was examined by TRAP staining in vitro. Bone formation
      was enhanced by the OCP composites with HyA90 and HyA600, compared to OCP alone,
      through enhanced osteoclastic resorption of OCP. HyA90 and HyA600 facilitated in
      vitro osteoclast formation. The results suggest that the osteoconductive property
      of OCP was accelerated by the HyAs-associated osteoclastic resorption of OCP, and
      therefore that HyA/OCP composites are attractive bone substitutes which are
      injectable and bioactive materials.

PMID- 24035889
TI  - A cluster randomized controlled trial of strategies to increase adolescents'
      physical activity and motivation in physical education: results of the Motivating
      Active Learning in Physical Education (MALP) trial.
AB  - OBJECTIVE: Physical education (PE) programs aim to promote physical activity (PA)
      and reach most school-aged youth. However, PA levels within PE lessons are often
      low. In this cluster-randomized controlled trial, we examined the effects of
      three self-determination theory-based motivational strategies on PA and sedentary
      behavior, as well as their hypothesized antecedents during PE lessons. METHODS:
      Data were collected in Sydney, Australia (October-December 2011). After baseline
      testing, teachers (n=16) and their classes (n=288 students; M=13.6 years, 50.4%
      male) were randomly assigned to one of four teaching strategy conditions: (1)
      explaining relevance; (2) providing choice; (3) complete free choice; or (4)
      usual practice. Teachers then delivered the assigned strategy. Primary outcomes
      were accelerometer-assessed PA and student motivation during lessons. Secondary
      outcomes included sedentary behavior, perceptions of teachers' support and
      psychological needs satisfaction. RESULTS: The 'free choice' intervention
      increased PA (p<.05). 'Providing choice' and 'free choice' interventions
      decreased sedentary behavior (p<.05). The interventions did not influence
      motivation, but students' autonomy increased during both choice-based
      interventions (p<.05). CONCLUSIONS: Promoting choice can produce short-term
      increases in PA and decreases in sedentary behavior, as well as increased
      perceived autonomy during PE lessons.

PMID- 24035890
TI  - Impact of sustaining a controlled residual growth on polyhydroxybutyrate yield
      and production kinetics in Cupriavidus necator.
AB  - In this study a complementary modeling and experimental approach was used to
      explore how growth controls the NADPH generation and availability, and the
      resulting impact on PHB (polyhydroxybutyrate) yields and kinetics. The results
      show that the anabolic demand allowed the NADPH production through the Entner
      Doudoroff (ED) pathway, leading to a high maximal theoretical PHB production
      yield of 0.89 C mole C mole(-1); whereas without biomass production, NADPH
      regeneration is only possible via the isocitrate dehydrogenase leading to a
      theoretical yield of 0.67 C mole C mole(-1). Furthermore, the maximum specific
      rate of NADPH produced at maximal growth rate (to fulfil biomass requirement) was
      found to be the maximum set in every conditions, which by consequence determines
      the maximal PHB production rate. These results imply that sustaining a controlled
      residual growth improves the PHB specific production rate without altering
      production yield.

PMID- 24035891
TI  - Techno-economical study of biogas production improved by steam explosion
      pretreatment.
AB  - Economic feasibility of steam explosion pretreatment for improvement of biogas
      production from wheat straw and paper tube residuals was investigated. The
      process was simulated by Aspen plus (r), and the economical feasibility of five
      different plant capacities was studied by Aspen Process Economic Analyzer. Total
      project investment of a plant using paper tube residuals or wheat straw was 63.9
      or 61.8 million Euros, respectively. The manufacturing cost of raw biogas for
      these two feedstocks was calculated to 0.36 or 0.48 ?/m(3) of methane,
      respectively. Applying steam explosion pretreatment resulted in 13% higher total
      capital investment while significantly improved the economy of the biogas plant
      and decreased the manufacturing cost of methane by 36%. The sensitivity analysis
      showed that 5% improvement in the methane yield and 20% decrease in the raw
      material price resulted in 5.5% and 8% decrease in the manufacturing cost of
      methane, respectively.

PMID- 24035892
TI  - Biosynthesis of poly(hydroxybutyrate-hydroxyvalerate) from the acclimated
      activated sludge and microbial characterization in this process.
AB  - This study investigated the effects of substrate composition (acetate and
      propionate) on synthesis of various mix of poly(hydroxybutyrate-hydroxyvalerate)
      (P(HB/HV)) from activated sludge, which was acclimated using a single carbon
      (acetate) and mixed carbons (acetate and propionate). Results of batch P(HB/HV)
      production tests indicated that the yield and synthesis rate of P(HB/HV)
      decreased as the proportion of propionate in the substrate increased. However,
      mixed-carbon-acclimated sludge with acetate and propionate exhibited better
      P(HB/HV) production performance than with acetate-acclimated sludge in terms of
      substrate utilization, yield of P(HB/HV) and HV fraction in P(HB/HV). The desired
      hydroxyvalerate (HV) fraction (0-74%) of the P(HB/HV) could be obtained based on
      the substrate composition and sludge acclimation. Furthermore, PCR-DGGE analysis
      indicated that specific species dominated the activated sludge used for P(HB/HV)
      production. Acidobacteria and Burkholderiales were the dominant bacterial
      populations and played an important role in HV synthesis. 

PMID- 24035893
TI  - Lack of association between COMT Val158Met polymorphism and late-onset
      Alzheimer's disease in Han Chinese.
AB  - COMT (catechol-O-methyltransferase) has been conjectured to be associated with
      Alzheimer's disease (AD) due to its key role in cognitive function impairment by
      influencing the dopamine degradation in prefrontal cortex. A functional single
      nucleotide polymorphism (rs4680 SNP; G to A) in the COMT coding region causes
      Val158Met amino acid substitution in the corresponding protein, with Val allele
      exhibiting markedly 3- to 4-fold higher than Met in enzyme activity. Recent study
      reported that the functional rs4680 polymorphism within COMT gene was associated
      with susceptibility to AD in Caucasians. In order to examine the association
      between polymorphism in COMT gene and late-onset AD (LOAD) in a Han Chinese
      group, we analyzed the genotype and allele distributions of the COMT rs4680
      polymorphism in a Han Chinese population consisting of 2291 individuals (1132
      LOAD patients and 1159 healthy controls). In the present study, we find no
      significant association between the COMT rs4680 polymorphism and LOAD, even after
      statistical adjustment for age, gender and apolipoprotein E (APOE) status in the
      total sample as well as stratification for APOE status. Our results indicated
      that the COMT Val158Met polymorphism may not play a major role in the development
      of LOAD in Han Chinese. 

PMID- 24035894
TI  - Decreased dendritic spine density as a consequence of tetanus toxin light chain
      expression in single neurons in vivo.
AB  - Tetanus toxin light chain has been used for some time as a genetically-encoded
      tool to inhibit neurotransmission and thereby dissect mechanisms underlying
      neural circuit formation and function. In addition to cleaving v-SNARE proteins
      involved in axonal neurotransmitter release, tetanus toxin light chain can also
      block activity-dependent dendritic exocytosis. The application of tetanus toxin
      light chain as a research tool in mammalian models, however, has been limited to
      a small number of cell types. Here we have induced expression of tetanus toxin
      light chain in a very small number of fluorescently labeled neurons in many
      regions of the adult mouse brain. This was achieved by crossing SLICK (single
      neuron labeling with inducible cre-mediated knockout) transgenic lines with
      RC::Ptox mice that have Cre recombinase-controlled expression of the tetanus
      toxin light chain. Using this system we have examined the cell-autonomous effects
      of tetanus toxin light chain expression on dendritic spines in vivo. We find that
      dendritic spine density is reduced by 15% in tetanus toxin expressing hippocampal
      CA1 pyramidal cells, while spine morphology is unaltered. This effect is likely
      to be a consequence of inhibition of activity-dependent dendritic exocytosis and
      suggests that on-going plasticity-associated exocytosis is required for long-term
      dendritic spine maintenance in vivo. 

PMID- 24035896
TI  - Oxysterols and Parkinson's disease: evidence that levels of 24S
      hydroxycholesterol in cerebrospinal fluid correlates with the duration of the
      disease.
AB  - Oxysterols are important for cholesterol homeostasis in the brain and may be
      affected in neurodegenerative diseases. The levels of the brain-derived oxysterol
      24S-hydroxycholesterol (24S-OH) have been reported to be markedly reduced in the
      circulation of patients with Parkinson's disease (PD) (Lee et al., Antioxid.
      Redox Signal. 11 (2009) 407-420). The finding is surprising in view of the fact
      that other neurodegenerative diseases are associated with relatively modest
      effects on the circulating levels of 24S-OH. We determined the plasma and
      cerebrospinal fluid (CSF) levels of 24S-OH and 27-hydroxycholesterol (27-OH) in
      patients with PD with different disease duration using a highly accurate method
      based on isotope dilution-mass spectrometry. All the patients had plasma levels
      of the different oxysterols within the normal range. When analyzing CSF, 10% of
      the PD patients were found to have levels of 24S-OH above the cut-off level and
      interestingly there was a significant correlation between levels of 24S-OH in CSF
      and duration of the disease (r=0.40, P<0.05). The CSF level of 27-OH was found to
      be above the cut-off level in 10% of the patients, indicating a defect blood
      brain barrier function. There was no correlation between levels of 27-OH in CSF
      and duration of the disease. These data indicates that oxysterol levels in CSF
      may be of value to follow disease progression. 

PMID- 24035895
TI  - Curcumin-induced upregulation of the anti-tau cochaperone BAG2 in primary rat
      cortical neurons.
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disease
      characterized by extracellular deposits of amyloid beta (Abeta) protein and
      intracellular neurofibrillary tangles of hyperphosphorylated tau protein. Various
      studies suggest that the tau tangle pathology, which lies downstream to Abeta
      pathology, is essential to produce AD-associated clinical phenotype and thus
      treatments targeting tau pathology may prevent or delay disease progression
      effectively. In this context, our present study examined three polyphenol
      compounds (curcumin, EGCG and resveratrol) for their possible activity against
      two endogenous proteins (BAG2 and LAMP1) that are shown to play a vital role in
      clearing tau tangles from neurons. Human epidemiological and animal data suggest
      potential positive effects of these polyphenols against AD. Here, primary rat
      cortical neurons treated with these polyphenols significantly up-regulated BAG2
      levels at different concentrations, while only EGCG upregulated LAMP1 levels,
      although at higher concentrations. Importantly, curcumin doubled BAG2 levels at
      low micromolar concentrations that are clinically relevant. In addition, curcumin
      also downregulated levels of phosphorylated tau, which may be potentially
      attributed to the curcumin-induced upregulation in BAG2 levels in the neurons.
      The present results demonstrate novel activity of polyphenol curcumin in up
      regulating an anti-tau cochaperone BAG2 and thus, suggest probable benefit of
      curcumin against AD-associated tauopathy. 

PMID- 24035897
TI  - Intrathecal inhibition of calcium/calmodulin-dependent protein kinase II in
      diabetic neuropathy adversely affects pain-related behavior.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) is considered an
      important enzyme contributing to the pathogenesis of persistent pain. The aim of
      this study was to test whether intrathecal injection of CaMKII inhibitors may
      reduce pain-related behavior in diabetic rats. Male Sprague-Dawley rats were
      used. Diabetes was induced with intraperitoneal injection of 55mg/kg
      streptozotocin. Two weeks after diabetes induction, CaMKII inhibitor myristoil
      AIP or KN-93 was injected intrathecally. Behavioral testing with mechanical and
      thermal stimuli was performed before induction of diabetes, the day preceding the
      injection, as well as 2h and 24h after the intrathecal injection. The expression
      of total CaMKII and its alpha isoform in dorsal horn was quantified using
      immunohistochemistry. Intrathecal injection of mAIP and KN-93 resulted in
      significant decrease in expression of total CaMKII and CaMKII alpha isoform
      activity. Also, mAIP and KN93 injection significantly increased sensitivity to a
      mechanical stimulus 24h after i.t. injection. Intrathecal inhibition of CaMKII
      reduced the expression of total CaMKII and its CaMKII alpha isoform activity in
      diabetic dorsal horn, which was accompanied with an increase in pain-related
      behavior. Further studies about the intrathecal inhibition of CaMKII should
      elucidate its role in nociceptive processes of diabetic neuropathy. 

PMID- 24035898
TI  - A systematic review and meta-analysis of surgical outcomes following mitral valve
      surgery in octogenarians: implications for transcatheter mitral valve
      interventions.
AB  - AIMS: To evaluate the outcomes of mitral valve surgery in octogenarians with
      severe symptomatic mitral regurgitation (MR). METHODS AND RESULTS: We performed a
      systematic review and meta-analysis of data on octogenarians who underwent mitral
      valve replacement (MVR) or mitral valve repair (MVRpr). Our search yielded 16
      retrospective studies. Using Bayesian hierarchical models, we estimated the
      pooled proportion of 30-day mortality, postoperative stroke, and long-term
      survival. The pooled proportion of 30-day postoperative mortality was 13%
      following MVR (10 studies, 3,105 patients, 95% credible interval [CI] 9-18%), and
      7% following MVRpr (six studies, 2,642 patients, 95% CI: 3-12%). Furthermore,
      pooled proportions of postoperative stroke were 4% (six studies, 2,945 patients,
      95% CI: 3-7%) and 3% (three studies, 348 patients, 95% CI: 1-8%) for patients
      undergoing MVR and MVRpr, respectively. Pooled survival rates at one and five
      years following MVR (four studies, 250 patients) were 67% (95% CI: 50-80%) and
      29% (95% CI: 16-47%), and following MVRpr (three studies, 333 patients) were 69%
      (95% CI: 50-83%) and 23% (95% CI: 12-39%), respectively. CONCLUSIONS: Surgical
      treatment of MR in octogenarians is associated with high perioperative mortality
      and poor long-term survival with an uncertain benefit on quality of life. These
      data highlight the importance of patient selection for operative intervention and
      suggest that future transcatheter mitral valve therapies such as transcatheter
      mitral valve repair (TMVr) and/or transcatheter mitral valve implantation (TMVI),
      may provide an alternative therapeutic approach in selected high-risk elderly
      patients.

PMID- 24035900
TI  - WITHDRAWN: Is microcephaly a so-far unrecognized feature of XYY syndrome?
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- 24035901
TI  - The expression pattern of the C-terminal kinesin gene kifc1 during the
      spermatogenesis of Sepiella maindroni.
AB  - In this study, we investigated the gene sequence and characteristic of kifc1 in
      Sepiella maindroni through PCR and RACE technology. Our research aimed
      particularly at the spatio-temporal expression pattern of kifc1 in the
      developmental testis through in situ hybridization. The particular role of kifc1
      in the spermatogenesis of S. maindroni was our particular interest. Based on
      multiple protein sequence alignments of KIFC1 homologues, kifc1 gene from the
      testis of S. maindroni was identified, which consisted of 2432bp including a 2109
      in-frame ORF corresponding to 703 continuous amino acids. The encoded polypeptide
      shared highest similarity with Octopus tankahkeei. Through the prediction of the
      secondary and tertiary structures, the motor domain of KIFC1 was conserved at the
      C-terminal, having putative ATP-binding and microtubule-binding motifs, while the
      N-terminal was more specific to bind various cargoes for cellular events. The
      stalk domain connecting between the C-terminal and N-terminal determined the
      direction of movement. According to RT-PCR results, the kifc1 gene is not tissue
      specific, commonly detected in different tissues, for example, the testis, liver,
      stomach, muscle, caecum and gills. Through an in situ hybridization method, the
      expression pattern of KIFC1 protein mimics in the spermatogenesis of S.
      maindroni. During the primary stage of the spermatogenesis, the kifc1 mRNA signal
      was barely detectable. At the early spermatids, the signal started to be present.
      With the elongation of spermatids, the signals increased substantially. It peaked
      and gathered around the acrosome area when the spermatids began to transform to
      spindle shape. As the spermatids developed into mature sperm, the signal
      vanished. In summary, the expression of kfic1 at specific stages during
      spermiogenesis and its distribution shed light on the potential functions of this
      motor in major cytological transformations. The KIFC1 homologue may provide a
      direct shaping force to the nucleus or influence the shaping process through
      indirect regulation. 

PMID- 24035899
TI  - Deconstructing stem cell population heterogeneity: single-cell analysis and
      modeling approaches.
AB  - Isogenic stem cell populations display cell-to-cell variations in a multitude of
      attributes including gene or protein expression, epigenetic state, morphology,
      proliferation and proclivity for differentiation. The origins of the observed
      heterogeneity and its roles in the maintenance of pluripotency and the lineage
      specification of stem cells remain unclear. Addressing pertinent questions will
      require the employment of single-cell analysis methods as traditional cell
      biochemical and biomolecular assays yield mostly population-average data. In
      addition to time-lapse microscopy and flow cytometry, recent advances in single
      cell genomic, transcriptomic and proteomic profiling are reviewed. The
      application of multiple displacement amplification, next generation sequencing,
      mass cytometry and spectrometry to stem cell systems is expected to provide a
      wealth of information affording unprecedented levels of multiparametric
      characterization of cell ensembles under defined conditions promoting
      pluripotency or commitment. Establishing connections between single-cell analysis
      information and the observed phenotypes will also require suitable mathematical
      models. Stem cell self-renewal and differentiation are orchestrated by the
      coordinated regulation of subcellular, intercellular and niche-wide processes
      spanning multiple time scales. Here, we discuss different modeling approaches and
      challenges arising from their application to stem cell populations. Integrating
      single-cell analysis with computational methods will fill gaps in our knowledge
      about the functions of heterogeneity in stem cell physiology. This combination
      will also aid the rational design of efficient differentiation and reprogramming
      strategies as well as bioprocesses for the production of clinically valuable stem
      cell derivatives. 

PMID- 24035902
TI  - Phenotypic expansion of the interstitial 16p13.3 duplication: a case report and
      review of the literature.
AB  - Genotype-phenotype analysis of at least 25 individuals with interstitial 16p13.3
      duplications defines a recognizable syndrome associated with duplication of a
      critical Rubinstein-Taybi region encompassing only the CREBBP gene. Nevertheless,
      variable or incompletely penetrant phenotype has been reported previously. We
      here report a case of a 5-year old boy with a recognizable phenotype of this
      syndrome, including intellectual disability, mild arthrogryposis, small and
      proximally implanted thumbs and characteristic facial features. In addition,
      growth delay, microcephaly and distinguishable structural brain MRI abnormalities
      were observed. A de novo 1.5 Mb interstitial duplication of 16p13.3 was detected
      by SNP-array and fluorescence in situ hybridization (FISH). Short tandem repeat
      polymorphism (STRP) analysis with marker D16S475 indicated that the duplication
      was formed before maternal meiosis II. Our findings highlight the variable
      clinical features and further expand the phenotypic spectrum correlated with this
      lately proposed syndrome.

PMID- 24035903
TI  - The -974C>A (rs3087459) gene polymorphism in the endothelin gene (EDN1) is
      associated with risk of developing acute coronary syndrome in Mexican patients.
AB  - Endothelial dysfunction plays an essential role in the development and
      progression of atherosclerotic lesions. Endothelial nitric oxide synthase (eNOS)
      and endothelin-1 (ET-1) are considered important molecules in the endothelial
      dysfunction process. The aim of the present study was to evaluate the role of
      eNOS and ET-1 (EDN1) gene polymorphisms as susceptibility markers for acute
      coronary syndrome (ACS). Six polymorphisms (rs1799983, rs2070744, rs1800783,
      rs3087459, rs1800541, and rs5369) of eNOS and EDN1 genes were analyzed by 5'
      exonuclease TaqMan genotyping assays in a group of 452 patients with ACS and 283
      healthy controls. The results showed increased frequencies of the A allele of the
      END1-914 C>A (rs3087459) polymorphism in ACS patients when compared to controls
      (OR=1.56, Pc=0.01). Under an additive model, the "AA" genotype was associated
      with an increased risk of developing ACS, adjusted for gender, hypertension,
      dyslipidemia, alcohol consumption, smoking, and diabetes (OR=1.56, p=0.045).
      Linkage disequilibrium analysis showed one EDN1 haplotype (AT) with increased
      frequency in ACS patients when compared to healthy controls (OR=1.65, Pc=0.0015).
      The "AT" haplotype was associated with the risk of developing ACS after adjusting
      for cardiovascular risk factors using multiple logistic analysis. In this case,
      the adjusted OR was 1.73 for the AT haplotype (Pc=0.0018). In summary, resulting
      data suggest that the END1-914 C>A gene polymorphism could be involved in the
      risk of developing ACS in Mexican individuals.

PMID- 24035905
TI  - The challenge of cancellations on the day of surgery.
AB  - INTRODUCTION: Cancellations of planned surgical procedures have been a major and
      long-standing problem for healthcare organisations across the world. They
      represent a significant loss of revenue and waste of resources, have significant
      psychological, social and financial implications for patients and their families
      and represent a significant loss of training opportunities for surgical trainees.
      The current study investigates the reasons for day of surgery cancellations at an
      NHS Foundation Trust in the United Kingdom and proposes strategies to reduce
      their incidence. METHODS: All cancellations of elective and emergency procedures
      during the period from January 2012 to December 2012 were identified
      retrospectively using the IQ Utopia patient management software. RESULTS: The
      rate of cancellations on the day of surgery for elective and planned emergency
      procedures during 2012 was 5.19%. The main reason for cancellation was patient
      not fit for operation (33.73%), followed by lack of beds (21.79%), lack of
      theatre time (17.31%), patient failed to attend (6.87%) and operation no longer
      necessary (4.08%). CONCLUSIONS: Similar reasons for cancellations have been
      reported in studies from around the world. The published literature provides
      various examples of successful and unsuccessful strategies to reduce surgery
      cancellations, even when they are caused by factors that are sometimes considered
      unavoidable. The feasibility and profitability of approaches that have been
      proven to be successful in other institutions should be assessed thoroughly in
      the context of the individual institution's characteristics and individual
      problems before a decision for implementation is made.

PMID- 24035904
TI  - Object-in-place associative recognition memory depends on glutamate receptor
      neurotransmission within two defined hippocampal-cortical circuits: a critical
      role for AMPA and NMDA receptors in the hippocampus, perirhinal, and prefrontal
      cortices.
AB  - Object-in-place associative recognition memory depends on an interaction between
      the hippocampus (HPC), perirhinal (PRH), and medial prefrontal (mPFC) cortices,
      yet the contribution of glutamate receptor neurotransmission to these
      interactions is unknown. NMDA receptors (NMDAR) in the HPC were critical for
      encoding of object-in-place memory but not for single-item object recognition.
      Next, a disconnection procedure was used to examine the importance of
      "concurrent" glutamate neurotransmission in the HPC-mPFC and HPC-PRH.
      Contralateral unilateral infusions of NBQX (AMPAR antagonist), into the HPC-mPFC,
      or HPC-PRH, either before acquisition or test, impaired object-in-place
      performance. Thus, both circuits are necessary for encoding and retrieval.
      Crossed unilateral AP5 (NMDAR antagonist) infusions into the HPC-mPFC or HPC-PRH
      impaired encoding, but not retrieval. Specifically crossed HPC-mPFC infusions
      impaired both short-term (5 min) and longer term (1 h) memory while HPC-PRH
      infusions impaired longer term memory only. This delay-dependent effect of AP5 in
      the HPC-PRH on object-in-place memory, accords with its effects in the PRH, on
      single item object recognition memory, thereby suggesting that a single PRH
      synaptic plasticity mechanism underpins different recognition memory processes.
      Further, blocking excitatory neurotransmission in any pair of structures within
      the networks impaired "both" encoding and retrieval, thus object-in-place memory
      clearly requires network interdependency across multiple structures. 

PMID- 24035906
TI  - Construction of circular miRNA sponges targeting miR-21 or miR-221 and
      demonstration of their excellent anticancer effects on malignant melanoma cells.
AB  - microRNA sponges antagonizing the oncogenic microRNAs are potential candidates
      for RNA-based cancer therapies. Although the constructed sponges so far are to
      some extent suitable for biological experiments, they can only express at
      relative low levels in cells, because they are sensitive to microRNA-mediated
      activation of deadenylation and subsequent exonucleolytic degradation. Since
      circular RNA molecules are resistant to exonuclease degradation, we report the
      production of circular microRNA sponges against miR-21 or miR-221 in cell lines
      using the self-splicing permuted intron-exon sequences derived from T4
      bacteriophage gene td. The circularized microRNA sponges withstand enzymatic
      degradation and are completely resistant to microRNA-mediated degradation. They
      are more effective than typical linear microRNA sponges and microRNA inhibitors
      in derepressing microRNA targets. They also display superior anti-cancer
      activities compared to the linear sponges in malignant melanoma cell lines. We
      have provided an alternative method for circular microRNA sponge production and
      malignant melanoma treatment. 

PMID- 24035907
TI  - Expression and regulation of glycogen synthase kinase 3 in human neutrophils.
AB  - Glycogen synthase kinase 3 (GSK-3) is a serine/threonine kinase involved in the
      regulation of cellular processes ranging from glycogen metabolism to cell cycle
      regulation. Its two known isoforms, alpha and beta, are differentially expressed
      in tissues throughout the body and exert distinct but often overlapping
      functions. GSK-3 is typically active in resting cells, inhibition by
      phosphorylation of Ser21 (GSK-3alpha) or Ser9 (GSK-3beta) being the most common
      regulatory mechanism. GSK-3 activity has been linked recently with immune system
      function, yet little is known about the role of this enzyme in neutrophils, the
      most abundant leukocyte type. In the present study, we examined GSK-3 expression
      and regulation in human neutrophils. GSK-3alpha was found to be the predominant
      isoform, it was constitutively expressed and cell stimulation with different
      agonists did not alter its expression. Stimulation by fMLP, LPS, GM-CSF, Fcgamma
      receptor engagement, or adenosine A2A receptor engagement all resulted in
      phosphorylation of Ser21. The use of metabolic inhibitors revealed that
      combinations of Src kinase, PKC, PI3K/AKT, ERK/RSK and PKA signaling pathways
      could mediate phosphorylation, depending on the agonist. Neither PLC nor p38 were
      involved. We conclude that GSK-3alpha is the main isoform expressed in
      neutrophils and that many different pathways can converge to inhibit GSK-3alpha
      activity via Ser21-phosphorylation. GSK-3alpha thus might be a hub of cellular
      regulation. 

PMID- 24035908
TI  - Toxicity induced by chemical warfare agents: insights on the protective role of
      melatonin.
AB  - Chemical Warfare Agents (CWAs) are substances that can be used to kill, injure or
      incapacitate an enemy in warfare, but also against civilian population in
      terrorist attacks. Many chemical agents are able to generate free radicals and
      derived reactants, excitotoxicity process, or inflammation, and as consequence
      they can cause neurological symptoms and damage in different organs. Nowadays,
      taking into account that total immediate decontamination after exposure is
      difficult to achieve and there are not completely effective antidotes and
      treatments against all CWAs, we advance and propose that medical countermeasures
      against CWAs poisoning would benefit from a broad-spectrum multipotent molecule.
      Melatonin, a versatile and ubiquitous antioxidant molecule, originally discovered
      as a hormone synthesized mainly in the pineal gland, has low toxicity and high
      efficacy in reducing oxidative damage, anti-inflammatory effects by regulation of
      multiple cellular pathways and properties to prevent excitotoxicity, among
      others. The purpose of this review is to show the multiple and diverse properties
      of melatonin, as a pleiotropic indole derivative, and its marked potential for
      improving human health against the most widely used chemical weapons. 

PMID- 24035909
TI  - Helicobacter pylori infection combined with DENA revealed altered expression of
      p53 and 14-3-3 isoforms in Gulo-/- mice.
AB  - Unlike most other mammals, human bodies do not have the ability to synthesize
      vitamin C inside of their own bodies. Therefore, humans must obtain vitamin C
      through daily diet. Gulo(-/-) mice strain is known with deficiency, in which
      vitamin C intake can be controlled by diet like human, and would be valuable for
      investigating the molecular mechanism of various diseases. In the present study,
      we established Gulo(-/-) mice model and investigated the differentially expressed
      proteins in stomach tissue of Gulo(-)(/-) mice after Helicobacter pylori
      infected, and followed by DENA, using immunohistochemistry and proteomic
      approach. The results of immunohistochemistry analysis of stomach tissue showed
      that the tumor suppressor, p53 protein, expression was significantly decreased
      (p<0.05) but not messenger RNA (mRNA) transcriptional level, and 14-3-3 epsilon,
      14-3-3 delta, Ki-67 and cleaved caspase 3 expressions were significantly
      increased (p<0.05) by H. Pylori infection, and followed by DENA treatment in
      Gulo(-/-) mice. Moreover, knockdown of 14-3-3 isoforms (14-3-3 epsilon, 14-3-3
      sigma, 14-3-3 zeta and 14-3-3 eta) were significantly increased sub-G1 phase
      (characteristics of apoptosis) in AGS cells and, phenotypic changes like cell
      shrinkage, density and cleaved nuclei were also observed. Proteome analyses
      showed that 14-3-3 sigma, 14-3-3 eta, and tropomyosin alpha-1 chain were down
      regulated, and Hspd1 protein and HSC70 were up-regulated after H. Pylori
      infection, and followed by DENA. The combined results of immunohistochemistry and
      proteomic analysis suggest that H. pylori altered the p53 and 14-3-3 isoforms
      expression and DENA further enhanced the H. pylori effect, which might be
      involved in carcinogenesis and metastasis of gastric cancer on Gulo(-/-) mice.

PMID- 24035910
TI  - Fate modeling of mercury species and fluxes estimation in an urban river.
AB  - The fate and transfer of mercury in urban river is an important environmental
      concern. In this study, QWASI (Quantitative Water-Air-Sediment Interaction) model
      was selected to estimate the levels of total mercury and three mercury species in
      water and sediment, and was used to quantify the fluxes of mercury at water/air
      and sediment/water interfaces of an urban river. The predicted mercury levels in
      water and sediments were closed to the measured values. Water inflow, re
      suspension of sediment and diffusion from sediment to water are major input
      sources of mercury in water. The net mercury transfer flux from water to air was
      0.16 ng/(m(2) h). At the sediment/water interface, a net total mercury transfer
      of 1.32 ng/(m(2) h) from water to sediment was seen. In addition to the existing
      dynamic flux chambers measurement, this model method could provide a new
      perspective to identify the distribution and transfer of mercury in the urban
      river. 

PMID- 24035911
TI  - Spatial distribution of mercury in southeastern Alaskan streams influenced by
      glaciers, wetlands, and salmon.
AB  - Southeastern Alaska is a remote coastal-maritime ecosystem that is experiencing
      increased deposition of mercury (Hg) as well as rapid glacier loss. Here we
      present the results of the first reported survey of total and methyl Hg (MeHg)
      concentrations in regional streams and biota. Overall, streams draining large
      wetland areas had higher Hg concentrations in water, mayflies, and juvenile
      salmon than those from glacially-influenced or recently deglaciated watersheds.
      Filtered MeHg was positively correlated with wetland abundance. Aqueous Hg
      occurred predominantly in the particulate fraction of glacier streams but in the
      filtered fraction of wetland-rich streams. Colonization by anadromous salmon in
      both glacier and wetland-rich streams may be contributing additional marine
      derived Hg. The spatial distribution of Hg in the range of streams presented here
      shows that watersheds are variably, yet fairly predictably, sensitive to
      atmospheric and marine inputs of Hg. 

PMID- 24035912
TI  - Impacts of simulated drought on pore water chemistry of peatlands.
AB  - Northern peatlands are increasingly threatened by climate change and industrial
      activities. This study examined the impact of simulated droughts on pore water
      chemistry at six peatlands in Sudbury, Ontario, that differ in copper (Cu),
      nickel (Ni) and cobalt (Co) contamination, including a site that had been
      previously limed. All sites responded similarly to simulated drought: pore water
      pH declined significantly following the 30 day drought and the decline was
      greater following the 60 day drought treatment. The decline in pore water pH was
      due to increasing sulphate concentrations, whereas nitrate increased more in the
      60 day drought treatment. Decreases in pH were accompanied by large increases in
      Ni and Co that greatly exceeded provincial water quality guidelines. In contrast,
      dissolved organic carbon (DOC) concentrations decreased significantly following
      drought, along with concentrations of Cu and Al, which are strongly complexed by
      organic acids. 

PMID- 24035913
TI  - First measurements of source apportionment of organic aerosols in the Southern
      Hemisphere.
AB  - An Aerodyne Aerosol Mass Spectrometer was deployed at five urban schools to
      examine spatial and temporal variability of organic aerosols (OA) and positive
      matrix factorization (PMF) used for the first time in the Southern Hemisphere to
      apportion the sources of the OA across an urban area. The sources identified
      included hydrocarbon-like OA (HOA), biomass burning OA (BBOA) and oxygenated OA
      (OOA). At all sites, the main source was OOA, which accounted for 62-73% of the
      total OA mass and was generally more oxidized compared to those reported in the
      Northern Hemisphere. This suggests that there are differences in aging processes
      or regional sources in the two hemispheres. Unlike HOA and BBOA, OOA demonstrated
      instructive temporal variations but not spatial variation across the urban area.
      Application of cluster analysis to the PMF-derived sources offered a simple and
      effective method for qualitative comparison of PMF sources that can be used in
      other studies. 

PMID- 24035915
TI  - Dose-dependent improvements in learning and memory deficits in APPPS1-21
      transgenic mice treated with the orally active Abeta toxicity inhibitor SEN1500.
AB  - In the Alzheimer's disease (AD) brain, accumulation of Abeta1-42 peptides is
      suggested to initiate a cascade of pathological events. To date, no treatments
      are available that can reverse or delay AD-related symptoms in patients. In the
      current study, we introduce a new Abeta toxicity inhibitor, SEN1500, which in
      addition to its block effect on Abeta1-42 toxicity in synaptophysin assays, can
      be administered orally and cross the blood-brain barrier without adverse effects
      in mice. In a different set of animals, APPPS1-21 mice were fed with three
      different doses of SEN1500 (1 mg/kg, 5 mg/kg and 20 mg/kg) for a period of 5
      months. Cognition was assessed in a variety of behavioral tests (Morris water
      maze, social recognition, conditioned taste aversion and passive avoidance).
      Results suggest a positive effect on cognition with 20 mg/kg SEN1500 compared to
      control APPPS1-21 mice. However, no changes in soluble or insoluble Abeta1-40 and
      Abeta1-42 were detected in the brains of SEN1500-fed mice. SEN1500 also
      attenuated the effect of Abeta1-42 on synaptophysin levels in mouse cortical
      neurons, which indicated that the compound blocked the synaptic toxicity of
      Abeta1-42. In vitro and in vivo effects presented here suggest that SEN1500 could
      be an interesting AD therapeutic. 

PMID- 24035914
TI  - 15 years of genetic approaches in vivo for addiction research: Opioid receptor
      and peptide gene knockout in mouse models of drug abuse.
AB  - The endogenous opioid system is expressed throughout the brain reinforcement
      circuitry, and plays a major role in reward processing, mood control and the
      development of addiction. This neuromodulator system is composed of three
      receptors, mu, delta and kappa, interacting with a family of opioid peptides
      derived from POMC (beta-endorphin), preproenkephalin (pEnk) and preprodynorphin
      (pDyn) precursors. Knockout mice targeting each gene of the opioid system have
      been created almost two decades ago. Extending classical pharmacology, these
      mutant mice represent unique tools to tease apart the specific role of each
      opioid receptor and peptide in vivo, and a powerful approach to understand how
      the opioid system modulates behavioral effects of drugs of abuse. The present
      review summarizes these studies, with a focus on major drugs of abuse including
      morphine/heroin, cannabinoids, psychostimulants, nicotine or alcohol. Genetic
      data, altogether, set the mu receptor as the primary target for morphine and
      heroin. In addition, this receptor is essential to mediate rewarding properties
      of non-opioid drugs of abuse, with a demonstrated implication of beta-endorphin
      for cocaine and nicotine. Delta receptor activity reduces levels of anxiety and
      depressive-like behaviors, and facilitates morphine-context association. pEnk is
      involved in these processes and delta/pEnk signaling likely regulates alcohol
      intake. The kappa receptor mainly interacts with pDyn peptides to limit drug
      reward, and mediate dysphoric effects of cannabinoids and nicotine.
      Kappa/dynorphin activity also increases sensitivity to cocaine reward under
      stressful conditions. The opioid system remains a prime candidate to develop
      successful therapies in addicted individuals, and understanding opioid-mediated
      processes at systems level, through emerging genetic and imaging technologies,
      represents the next challenging goal and a promising avenue in addiction
      research. This article is part of a Special Issue entitled 'NIDA 40th Anniversary
      Issue'.

PMID- 24035917
TI  - Targeting the unfolded protein response in neurodegeneration: A new approach to
      therapy.
AB  - Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease
      (PD), Huntington's disease (HD), and the rarer prion diseases, share a number of
      key similarities, including aggregation of disease-specific proteins in the brain
      and neuronal loss. The focus of research in these disorders has centred on
      pathogenesis caused by individual proteins and their build up in their specific
      diseases, but there are also likely to be more generic pathways that are active
      in neurodegeneration across the spectrum of these disorders. The unfolded protein
      response (UPR) has recently emerged as one such pathway. The UPR is normally a
      protective cellular response that protects against endoplasmic reticulum (ER)
      stress, which occurs with the build up of misfolded proteins. Recent evidence
      indicates that in neurodegenerative disease this pathway becomes constitutively
      activated, preventing protein translation. UPR activation is found in post mortem
      brains in a variety of diseases, including AD, PD and prion diseases, and has
      also been found to be activated in mouse models of neurodegeneration and in
      various in vitro models. We propose that modulation of the UPR in
      neurodegeneration is therefore a promising target for future therapeutic
      treatments. This article is part of the Special Issue entitled 'The Synaptic
      Basis of Neurodegenerative Disorders'. 

PMID- 24035916
TI  - Synergistic activity between the delta-opioid agonist SNC80 and amphetamine
      occurs via a glutamatergic NMDA-receptor dependent mechanism.
AB  - Glutamate is known to cause the release of dopamine through a Ca(2+)-sensitive
      mechanism that involves activation of NMDA ionotropic glutamate receptors. In the
      current study, we tested the hypothesis that the delta opioid agonist SNC80 acts
      indirectly, via the glutamatergic system, to enhance both amphetamine-stimulated
      dopamine efflux from striatal preparations and amphetamine-stimulated locomotor
      activity. SNC80 increased extracellular glutamate content, which was accompanied
      by a concurrent decrease in GABA levels. Inhibition of NMDA signaling with the
      selective antagonist MK801 blocked the enhancement of both amphetamine-induced
      dopamine efflux and hyperlocomotion observed with SNC80 pretreatment. Addition of
      exogenous glutamate also potentiated amphetamine-stimulated dopamine efflux in a
      Mg(2+)- and MK801-sensitive manner. After removal of Mg(2+) to relieve the ion
      conductance inhibition of NMDA receptors, SNC80 both elicited dopamine release
      alone and produced a greater enhancement of amphetamine-evoked dopamine efflux.
      The action of SNC80 to enhance amphetamine-evoked dopamine efflux was mimicked by
      the GABA(B) antagonist 2-hydroxysaclofen. These cumulative findings suggest SNC80
      modulates amphetamine-stimulated dopamine efflux through an intra-striatal
      mechanism involving inhibition of GABA transmission leading to the local release
      of glutamate followed by subsequent activation of NMDA receptors.

PMID- 24035918
TI  - AMPA receptor upregulation in the nucleus accumbens shell of cocaine-sensitized
      rats depends upon S-nitrosylation of stargazin.
AB  - Behavioral sensitization to cocaine is associated with increased AMPA receptor
      (AMPAR) surface expression in the nucleus accumbens (NAc). This upregulation is
      withdrawal-dependent, as it is not detected on withdrawal day (WD) 1, but is
      observed on WD7-21. Its underlying mechanisms have not been clearly established.
      Nitric oxide (NO) regulates AMPAR trafficking in the brain by S-nitrosylation of
      the AMPAR auxiliary subunit, stargazin, leading to increased AMPAR surface
      expression. Our goal was to determine if stargazin S-nitrosylation contributes to
      AMPAR upregulation during sensitization. First, we measured stargazin S
      nitrosylation in NAc core and shell subregions on WD14 after 8 daily injections
      of saline or 15 mg/kg cocaine. Stargazin S-nitrosylation was markedly increased
      in NAc shell but not core. To determine if this is associated with AMPAR
      upregulation, rats received 8 cocaine or saline injections followed by twice
      daily treatments with vehicle or the nitric oxide synthase inhibitor l-NAME (50
      mg/kg) on WD1-6, the time when AMPAR upregulation is developing in cocaine
      exposed rats. Cocaine/vehicle rats showed elevated stargazin and GluA1 surface
      expression on WD7 compared to saline/vehicle rats; the GluA1 increase was more
      robust in core, while stargazin increased more robustly in shell. These effects
      of cocaine were attenuated in shell but not core when cocaine injections were
      followed by l-NAME treatment on WD1-6. Together, these results indicate that
      elevated S-nitrosylation of stargazin contributes to AMPAR upregulation during
      sensitization selectively in the NAc shell. It is possible that AMPAR
      upregulation in core involves a different TARP, gamma4, which also upregulates in
      the NAc of sensitized rats.

PMID- 24035919
TI  - Parkinson's disease in a dish - Using stem cells as a molecular tool.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease,
      with a strong genetic component to both the familial and sporadic forms. The
      cardinal motor symptoms of the disease result from the loss of dopamine (DA)
      neurons in the midbrain. There is currently no cure for PD and improved methods
      for modelling the disease are required in order to develop more effective
      therapeutic interventions. Patient-derived induced pluripotent stem cells (iPSCs)
      carry the genetic background of the donor, enabling accurate modelling of genetic
      diseases in vitro. Various human iPSCs from patients suffering different genetic
      forms of PD have been differentiated into DA neurons and demonstrated signs of
      the pathophysiology of PD in vitro. The examination of key cellular pathways such
      as calcium regulation and autophagy indicate that disease-associated genetic
      variants may have important implications for cellular function. This review
      examines and critiques how DA neurons from patient iPSCs have been used to model
      PD in vitro, and what iPSCs might hold for the future of PD research. This
      article is part of the Special Issue entitled 'The Synaptic Basis of
      Neurodegenerative Disorders'. 

PMID- 24035920
TI  - The effects of propofol on mitochondrial dysfunction following focal cerebral
      ischemia-reperfusion in rats.
AB  - Propofol has been shown to attenuate brain injury in experimental ischemia
      models, but few studies have focused on the direct effect of propofol on
      mitochondrial dysfunction. In this study, we observed the effects of propofol on
      multiple aspects of mitochondrial dysfunction by studying the mitochondria
      isolated from rat brains subjected to focal cerebral ischemia-reperfusion. The
      mitochondria of the cortical tissue were isolated by the Percoll density gradient
      centrifugation. The isolated mitochondria were fixed and examined with electron
      microscopy. The calcium-induced mitochondrial swelling was quantified by
      measuring the decrease in light transmission at 540 nm with a spectrometer.
      Fluorescent probes were used to selectively stain mitochondria. Flow cytometry
      was used to measure the membrane potential and the production of reactive
      oxidative species. Propofol improved the signs of injury in the cortical
      mitochondria that were exposed to reperfusion following 2 h of focal ischemia.
      Propofol prevented calcium-induced mitochondrial swelling in a concentration
      dependent manner. It did not affect the reperfusion-induced reduction in
      mitochondrial membrane potential. However, it decreased the production of the
      mitochondrial reactive oxidative species, which are generated during reperfusion.
      These results demonstrate that propofol may protect against mitochondrial
      dysfunction by preventing the ultrastructural change to the mitochondria and the
      calcium-induced mitochondrial swelling. This protective effect may be mediated by
      inhibiting the mitochondrial membrane permeability transition and reducing the
      production of reactive oxidative species in mitochondria.

PMID- 24035921
TI  - Effects of selective and non-selective inhibitors of nitric oxide synthase on
      morphine- and endomorphin-1-induced analgesia in acute and neuropathic pain in
      rats.
AB  - Nitric oxide (NO) has been reported to be involved in the mechanisms of pain
      generation throughout the nervous system. We examined the effects of
      intrathecally (i.t.) administered nitric oxide synthase (NOS) inhibitors on the
      antinociceptive effects of morphine and endomorphin-1 during acute pain and in
      chronic constriction injury (CCI)-exposed rats. We used N(G)-nitro-l-arginine
      methyl ester (l-NAME), a non-selective NOS inhibitor; 7-nitroindazole (7-NI) or 1
      (2-trifluoromethyl-phenyl)-imidazole (TRIM), selective inhibitors of neuronal NOS
      (NOS1); and 1400W dihydrochloride, a selective inhibitor of inducible NOS (NOS2).
      Morphine (0.5-2.5 MUg) and endomorphin-1 (2.5-20 MUg) in acute pain and morphine
      (10-40 MUg) and endomorphin-1 (5-20 MUg) after CCI-injury were combined with NOS
      inhibitors. For acute pain, the ED50 for endomorphin-1 (7.1 MUg) was higher than
      that of morphine (1.3 MUg) in the tail-flick test. For neuropathic pain, the ED50
      value for morphine was much higher (43.2 MUg) than that of endomorphin-1 (9.2
      MUg) in von Frey test. NOS inhibitors slightly influenced pain thresholds in both
      pain models. Moreover, in neuropathic pain, the effects of morphine were more
      potentiated by L-NAME, TRIM, 7-NI and 1400W (12*, 8.6*, 4.1* and 5.3*,
      respectively) than were the effects of endomorphin-1 (2.7*, 4.3*, 3.4* and 2.1*,
      respectively) in the von Frey test. Minocycline which is known to enhance the
      efficiency of morphine in neuropathic pain, decreased the mRNA expression of NOS1
      in the DRG and NOS2 and C1q in the spinal cord after CCI. Both NOS2 and IBA-1
      protein levels in the spinal cord and NOS1, NOS2 and IBA1 protein levels in DRG
      decreased after minocycline administration. In conclusion, our results provide
      evidence that both neuronal and non-neuronal NOS/NO pathways contribute to the
      behavioural pain responses evoked by nerve injury. The NOS inhibitors regardless
      of the type of pain enhanced morphine antinociception and, to a lesser extent,
      altered the effects of endomorphin-1, an opioid ligand with a peptidergic
      structure.

PMID- 24035922
TI  - Different ataxin-3 amyloid aggregates induce intracellular Ca(2+) deregulation by
      different mechanisms in cerebellar granule cells.
AB  - This work aims at elucidating the relation between morphological and
      physicochemical properties of different ataxin-3 (ATX3) aggregates and their
      cytotoxicity. We investigated a non-pathological ATX3 form (ATX3Q24), a
      pathological expanded form (ATX3Q55), and an ATX3 variant truncated at residue
      291 lacking the polyQ expansion (ATX3/291Delta). Solubility, morphology and
      hydrophobic exposure of oligomeric aggregates were characterized. Then we
      monitored the changes in the intracellular Ca(2+) levels and the abnormal Ca(2+)
      signaling resulting from aggregate interaction with cultured rat cerebellar
      granule cells. ATX3Q55, ATX3/291Delta and, to a lesser extent, ATX3Q24 oligomers
      displayed similar morphological and physicochemical features and induced
      qualitatively comparable time-dependent intracellular Ca(2+) responses. However,
      only the pre-fibrillar aggregates of expanded ATX3 (the only variant which forms
      bundles of mature fibrils) triggered a characteristic Ca(2+) response at a later
      stage that correlated with a larger hydrophobic exposure relative to the two
      other variants. Cell interaction with early oligomers involved glutamatergic
      receptors, voltage-gated channels and monosialotetrahexosylganglioside (GM1)-rich
      membrane domains, whereas cell interaction with more aged ATX3Q55 pre-fibrillar
      aggregates resulted in membrane disassembly by a mechanism involving only GM1
      rich areas. Exposure to ATX3Q55 and ATX3/291Delta aggregates resulted in cell
      apoptosis, while ATX3Q24 was substantially innocuous. Our findings provide
      insight into the mechanisms of ATX3 aggregation, aggregate cytotoxicity and
      calcium level modifications in exposed cerebellar cells. 

PMID- 24035923
TI  - Influence of skin closure technique on surgical site infection after loop
      ileostomy reversal: retrospective cohort study.
AB  - BACKGROUND: Intestinal stoma closure is associated with high risk of surgical
      site infection (SSI) at stoma reversal site. The aim of this retrospective cohort
      study was to determine the outcome of purse string approximation (PSA) compared
      to primary linear closure (PLC) of the skin after loop ileostomy reversal.
      METHODS: Data of 140 patients operated between 2005 and 2012 were analyzed in
      this two-center-study to determine the outcome of patients with either PSA (n =
      44) or PLC (n = 96) after loop ileostomy reversal. RESULTS: Patients in the PSA
      group were significantly older than in the PLC group (64 +/- 15 vs. 57 +/- 18; p
      = 0.026). Cardiac diseases were significantly more present in the PSA group in
      comparison to the PLC group (59% vs. 38%; p = 0.017). Stoma creation was
      significantly more often due to malignancy in the PSA group in comparison to the
      PLC group (68% vs. 50%; p = 0.044). SSI occurred significantly more often in the
      PLC group in comparison to the PSA group (17% vs. 5%; p = 0.047). CONCLUSIONS:
      The risk for SSI is lower in patients with PSA in comparison to patients with
      PLC. In order to diminish SSI we recommend performing a PSA in patients with loop
      ileostomy reversal.

PMID- 24035924
TI  - Poly (lactide-co-glycolide) nano-encapsulation of chelidonine, an active
      bioingredient of greater celandine (Chelidonium majus), enhances its ameliorative
      potential against cadmium induced oxidative stress and hepatic injury in mice.
AB  - This study evaluates the possible protective potentials of chelidonine and its
      poly lactide-co-glycolide (PLGA) encapsulated nano-form against cadmium chloride
      (CdCl2) induced oxidative stress and hepatotoxicity in mice, ex vivo and in vivo.
      Acute exposure to CdCl2 (1.0 mg/kg b.w; i.p., twice a week for 30 days) generated
      oxidative stress in mice through accumulation of reactive oxygen species and
      increased lipid peroxidation, and levels of certain liver marker enzymes (ALT,
      AST, ALP) with decrease in levels of GSH and certain other antioxidant enzymes
      (SOD, CAT, GR) in liver. Treatment with nano-chelidonine for 30 days after CdCl2
      intoxication significantly reduced oxidative stress and lipid peroxidation and
      restored levels of GSH, cholesterol, triglyceride and antioxidant enzymes,
      showing ameliorative changes in histopathology of liver. Expression pattern of
      certain inflammatory and apoptotic signal proteins also indicated better hepato
      protective abilities of nano-chelidonine, making it a more suitable protective
      drug than chelidonine against cadmium toxicity in mice.

PMID- 24035925
TI  - Effects of formaldehyde exposure on human NK cells in vitro.
AB  - Natural killer (NK) cells play a pivotal role in human immunologic surveillance.
      Formaldehyde (FA), a ubiquitous environmental contaminant, has been classified as
      a carcinogen to humans. Although it is known that immune cells are sensitive to
      FA, so far little is known about how it's affecting the activity of human NK
      cells. To probe it, the primary human NK cells were treated with different
      concentrations of FA (3200, 1600, 800, 400, 200, 100, 50, and 0 MUM) in vitro.
      The morphology, viability, apoptosis, cytotoxicity (killing tumor cell activity)
      and cytokine and cytolytic proteins secretion of NK cells were evaluated
      respectively. Our results reveal that FA could induce NK cells death obviously in
      a concentration-dependent manner. With the decreased concentrations of FA from
      3200 MUM to 800 MUM, accordingly, the viability of NK cells increased from 65. 2
      +/- 12.1% to 78.48 +/- 10.3% (p<0.05), and the cytotoxicity of NK cells recovered
      from 29.2 +/- 8.5% to 63.9 +/- 5.9% (p<0.05). The secretion of perforin was
      affected significantly by FA, whereas the secretion of IFN-gamma and granzyme-B
      altered slightly. It is concluded that human NK cell is sensitive to FA, 800 MUM
      may be a critical concentration of FA inhibiting the activity of human NK cell.

PMID- 24035928
TI  - Measurement and analysis of gamma-rays emitted from spent nuclear fuel above 3
      MeV.
AB  - The gamma-ray spectrum of spent nuclear fuel in the 3-6 MeV energy range is
      important for active interrogation since gamma rays emitted from nuclear decay
      are not expected to interfere with measurements in this energy region. There is,
      unfortunately, a dearth of empirical measurements from spent nuclear fuel in this
      region. This work is an initial attempt to partially fill this gap by presenting
      an analysis of gamma-ray spectra collected from a set of spent nuclear fuel
      sources using a high-purity germanium detector array. This multi-crystal array
      possesses a large collection volume, providing high energy resolution up to 16
      MeV. The results of these measurements establish the continuum count-rate in the
      energy region between 3 and 6 MeV. Also assessed is the potential for peaks from
      passive emissions to interfere with peak measurements resulting from active
      interrogation delayed emissions. As one of the first documented empirical
      measurements of passive emissions from spent fuel for energies above 3 MeV, this
      work provides a foundation for active interrogation model validation and detector
      development.

PMID- 24035927
TI  - Screening for early detection of parkinsonism using a self-administered
      questionnaire: a cross-sectional epidemiologic study.
AB  - BACKGROUND: Manganese (Mn) is a common component of welding fume. Exposure to Mn
      fume has been associated with parkinsonism. A simple and reliable screening tool
      to evaluate Mn exposed workers for neurotoxic injury would have broad
      occupational health application. METHODS: This study investigated 490
      occupational welders recruited from a trade union list. Subjects were examined by
      a movement disorders specialist using the Unified Parkinson Disease Rating Scale
      motor subsection 3 (UPDRS3). Parkinsonism, intermediate, and normal groups were
      defined as UPDRS3 score >= 15, 6-15, and <6, respectively. Workers completed a
      health status questionnaire (PDQ39) and a Parkinson disease (PD) Symptoms
      Questionnaire. Areas under receiver operator curve (AUC) were analyzed based on
      these scores, adjusted for age, smoking, race, gender, and neurologist, using
      normal as the reference. RESULTS: The AUC was 0.79 (95% confidence interval
      [CI]=0.73-0.84) for PDQ39 and 0.78 (95% CI=0.72-0.85) for PD Symptoms
      Questionnaire score. At 70% sensitivity, the specificity for PDQ39 score and PD
      Symptoms Questionnaire score for the prediction of parkinsonism was 73.1% and
      80.1%, respectively. CONCLUSIONS: These results suggest the questionnaires have
      reasonably good sensitivity and specificity to predict parkinsonism in Mn exposed
      workers. These questionnaires could be a valuable first step in a tiered
      screening approach for Mn exposed workers.

PMID- 24035929
TI  - Thermoluminescence properties of nanophosphors BaSO4:Dy and BaSO4:Tb.
AB  - Nanocrystalline BaSO4:Dy and BaSO4:Tb were prepared by the coprecipitation
      method. The materials were characterized with X-ray diffractometry, UV-visible
      spectroscopy, and scanning electron microscopy. The glow curves of the BaSO4:Dy
      and BaSO4:Tb nanophosphors feature main peaks at 505 K and 480 K, respectively.
      The responses to the (60)Co dose are linear in the range 0.1-1 kGy for BaSO4:Dy
      and in the range 0.1-7 kGy for BaSO4:Tb. The energy dependences of the responses
      were also studied.

PMID- 24035926
TI  - Bortezomib alters microtubule polymerization and axonal transport in rat dorsal
      root ganglion neurons.
AB  - Bortezomib is part of a newer class of chemotherapeutic agents whose mechanism of
      action is inhibition of the proteasome-ubiquitination system. Primarily used in
      multiple myeloma, bortezomib causes a sensory-predominant axonal peripheral
      neuropathy in approximately 30% of patients. There are no established useful
      preventative agents for bortezomib-induced peripheral neuropathy (BIPN), and the
      molecular mechanisms of BIPN are unknown. We have developed an in vitro model of
      BIPN using rat dorsal root ganglia neuronal cultures. At clinically-relevant
      dosages, bortezomib produces a sensory axonopathy as evidenced by whole explant
      outgrowth and cell survival assays. This sensory axonopathy is associated with
      alterations in tubulin and results in accumulation of somatic tubulin without
      changes in microtubule ultrastructure. Furthermore, we observed an increased
      proportion of polymerized tubulin, but not total or acetylated tubulin, in
      bortezomib-treated DRG neurons. Similar findings are observed with lactacystin,
      an unrelated proteasome-inhibitor, which argues for a class effect of proteasome
      inhibition on dorsal root ganglion neurons. Finally, there is a change in axonal
      transport of mitochondria induced by bortezomib in a time-dependent fashion. In
      summary, we have developed an in vitro model of BIPN that recapitulates the
      clinical sensory axonopathy; this model demonstrates that bortezomib induces an
      alteration in microtubules and axonal transport. This robust model will be used
      in future mechanistic studies of BIPN and its prevention. 

PMID- 24035930
TI  - Molecular genetic assay of mucopolysaccharidosis IVA in South China.
AB  - Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage
      disorder caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase
      (GALNS). Molecular mutational analysis was performed by PCR product sequencing
      for fourteen exons and exon-intron boundaries of GALNS gene in 21 patients from
      19 unrelated families with severe MPS IVA in South China. We identified fifteen
      different mutations, including 10 reported mutations (p.P125L, p.G290S, p.M318R,
      p.G340D, p.L366P, p.R386C, p.A392V, c.1243-1G>C, p.L440RfsX54 and p.X523E) and
      five novel mutations (p.N177S, p.G290R, p.F306S, p.W403_T404delinsCS, p.W520X).
      All five novel mutations were inherited from parents of the patients and not
      found in 100 normal control alleles. Three mutations, p.M318R, p.L366P and
      p.R386C were common, accounting for 36.8% of mutant alleles investigated. One
      patient homozygous of p.A392V and the other two unrelated patients homozygous of
      p.L366P presented classical disease course. The results show that the GALNS gene
      has a different mutational spectrum in South China as compared to other regions.
      The p.A392V and p.L366P mutations were associated with severe phenotype of MPS
      IVA. 

PMID- 24035931
TI  - Mmu-miR-702 functions as an anti-apoptotic mirtron by mediating ATF6 inhibition
      in mice.
AB  - MicroRNAs (miRNAs) are a group of endogenous, small, noncoding RNAs that function
      as key post-transcriptional regulators. miRNAs are involved in many biological
      processes including apoptosis. In this study, mouse miR-702 (mmu-miR-702), a
      mirtron derived from the 13th intron of the Plod3 gene, was identified as a
      regulator of anti-apoptosis. mmu-miR-702 was down-regulated after treatment with
      the apoptosis-inducer isoproterenol both in vivo and in vitro. According to over
      expression experiments, mmu-miR-702 inhibited apoptosis as well as the expression
      levels of a subset of apoptosis-related genes including activating transcription
      factor 6 (ATF6). An interaction between mmu-miR-702 and the ATF6 3'-UTR binding
      site was confirmed using luciferase reporter and western blot assays. This is the
      first report of ATF6 interaction with miRNA. Although the possible existence of
      miR-702 in the human genome is low, our results indicate that mirtrons also
      participate in the process of apoptosis and may provide a novel study strategy
      for apoptosis. 

PMID- 24035932
TI  - Frequency of genetic polymorphisms of ADAM33 and their association with allergic
      rhinitis among Jordanians.
AB  - Allergic rhinitis is a chronic inflammatory disease that is assumed to be due to
      an interaction between different genetic and/or environmental factors. A
      disintegrin and metalloprotease domain 33 (ADAM33) has been extensively studied
      as a susceptibility gene in asthma and has been linked to bronchial hyper
      responsiveness. In this study, we investigated the association between ADAM33
      single nucleotide polymorphisms and the incidence of allergic rhinitis among the
      Jordanian population. We conducted a case-control association study on 120 adult
      individuals diagnosed with allergic rhinitis and 128 normal healthy controls. 8
      single-nucleotide polymorphisms in ADAM33 were genotyped using PCR-RFLP method.
      No significant differences in the allelic frequencies of all SNPs tested between
      AR patients and the control volunteers were found, although S2 C/G SNP showed a
      tendency toward significance with P=0.06. On the genotype level significant
      association were found in the following genotypes: T1 AA, T1 AG, T2 GG, T2 AG,
      T+1 GG, T+1 AG, V4 CG, S2 CC, S2 CG, Q-1AA. Seven haplotypes were present only
      within AR patients and eight haplotypes were completely absent from the AR
      patients. Three haplotypes exhibited significant association with AR P <= 0.05,
      two of them were present only in AR patients. In conclusion, the polymorphisms in
      the ADAM33 gene are associated with susceptibility to AR in the Jordanian
      population. Furthermore, the haplotype of the tested SNPs were also associated
      with the risk of AR.

PMID- 24035933
TI  - Disturbance of brain energy and redox homeostasis provoked by sulfite and
      thiosulfate: potential pathomechanisms involved in the neuropathology of sulfite
      oxidase deficiency.
AB  - Sulfite oxidase (SO) deficiency is biochemically characterized by tissue
      accumulation and high urinary excretion of sulfite, thiosulfate and S
      sulfocysteine. Affected patients present severe neurological symptoms and
      cortical atrophy, whose pathophysiology is still poorly established. Therefore,
      in the present work we investigated the in vitro effects of sulfite and
      thiosulfate on important parameters of energy metabolism in the brain of young
      rats. We verified that sulfite moderately inhibited the activity of complex IV,
      whereas thiosulfate did not alter any of the activities of the respiratory chain
      complexes. It was also found that sulfite and thiosulfate markedly reduced the
      activity of total creatine kinase (CK) and its mitochondrial and cytosolic
      isoforms, suggesting that these metabolites impair brain cellular energy
      buffering and transfer. In contrast, the activity of synaptic Na(+),K(+)-ATPase
      was not altered by sulfite or thiosulfate. We also observed that the inhibitory
      effect of sulfite and thiosulfate on CK activity was prevented by melatonin,
      reduced glutathione and the combination of both antioxidants, as well as by the
      nitric oxide synthase N(omega)-nitro-l-arginine methyl ester, indicating the
      involvement of reactive oxygen and nitrogen species in these effects. Sulfite and
      thiosulfate also increased 2',7'-dichlorofluorescin oxidation and hydrogen
      peroxide production and decreased the activity of the redox sensor aconitase
      enzyme, reinforcing a role for oxidative damage in the effects elicited by these
      metabolites. It may be presumed that the disturbance of cellular energy and redox
      homeostasis provoked by sulfite and thiosulfate contributes to the neurological
      symptoms and abnormalities found in patients affected by SO deficiency. 

PMID- 24035934
TI  - FoxP3 genetic variants and risk of non-small cell lung cancer in the Chinese Han
      population.
AB  - CD4(+)CD25(+) regulatory T cell-mediated immunosuppression is one of the crucial
      mechanisms that tumor cells use to evade the immune system. The forkhead box P3
      (FoxP3) gene regulates regulatory T-cell development and function and may
      modulate the susceptibility to non-small cell lung cancer (NSCLC). Because a
      single nucleotide polymorphism (SNP) within the FoxP3 gene (rs3761548 in the
      promoter region) is associated with susceptibility to Graves' disease, this study
      detected rs3761548 in a hospital-based case-control study. A total of 192 NSCLC
      patients and 259 healthy subjects were recruited for the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of FoxP3
      SNP. The data showed that the A allele of rs3761548 significantly increased NSCLC
      risk (P=0.000, OR=2.32, 95%CI=1.736-3.102). The AC genotype, AA genotype, and the
      combined A variant genotype (AA+AC) were also associated with a higher risk of
      NSCLC (OR [95%CI]=2.147[1.419-3.247], 4.413[2.359-8.255], and 2.563[1.746-3.761],
      respectively). Moreover, a significantly higher frequency of AA+AC genotype was
      observed in patients with stage II NSCLC (OR, 2.053; 95%CI, 1.033-4.078). In
      conclusion, the data from the current study demonstrated for the first time the
      association of the FoxP3 SNP with a risk of developing NSCLC in the Chinese Han
      population. 

PMID- 24035935
TI  - Cloning of TPS gene from eelgrass species Zostera marina and its functional
      identification by genetic transformation in rice.
AB  - The full-length cDNA sequence (2613 bp) of the trehalose-6-phosphate synthase
      (TPS) gene of eelgrass Zostera marina (ZmTPS) was identified and cloned. Z.
      marina is a kind of seed-plant growing in sea water during its whole life
      history. The open reading frame (ORF) region of ZmTPS gene encodes a protein of
      870 amino acid residues and a stop codon. The corresponding genomic DNA sequence
      is 3770 bp in length, which contains 3 exons and 2 introns. The ZmTPS gene was
      transformed into rice variety ZH11 via Agrobacterium-mediated transformation
      method. After antibiotic screening, molecular characterization, salt-tolerance
      and trehalose content determinations, two transgenic lines resistant to 150 mM
      NaCL solutions were screened. Our study results indicated that the ZmTPS gene was
      integrated into the genomic DNA of the two transgenic rice lines and could be
      expressed well. Moreover, the detection of the transformed ZmTPS gene in the
      progenies of the two transgenic lines was performed from T1 to T4 generations;
      and results suggested that the transformed ZmTPS gene can be transmitted from
      parent to the progeny in transgenic rice.

PMID- 24035936
TI  - A one-step RT-PCR assay to detect and discriminate porcine reproductive and
      respiratory syndrome viruses in clinical specimens.
AB  - Outbreaks of highly pathogenic porcine reproductive and respiratory syndrome
      virus (HP-PRRSV) have led to large economic losses and, subsequently, have drawn
      great attention to its diagnosis and prevention. To facilitate rapid
      discrimination of HP-PRRSV from classical PRRSV (C-PRRSV), we developed a one
      step RT-PCR assay. Primer specificities were evaluated with RNA extracted from 8
      viral strains and our results revealed that the primers had a high specificity
      for PRRSV. The assay sensitivity was 25 copies/MUL for both HP-PRRSV and C-PRRSV.
      A total of 929 serum samples were identified, of which 20.45% were HP-PRRSV
      positive and 1.51% were C-PRRSV-positive, which was completely consistent with
      that of immunochromatochemistry and sequencing method. The proposed assay can
      detect the virus 2 days prior the onset of symptoms and it can be performed in
      2h, thereby providing a rapid method to discriminate HP-PRRSV from C-PRRSV for
      the identification and prevention of PRRSV infections.

PMID- 24035937
TI  - In vitro and ex vivo angiogenic effects of roxarsone on rat endothelial cells.
AB  - Roxarsone, a feed additive, is being used worldwide to promote animal growth.
      However, the potential effect of roxarsone on angiogenesis has not been
      extensively characterized. We examined the ability of roxarsone to promote
      angiogenesis of rat endothelial cells in vitro and from rat aorta rings ex vivo.
      Endothelial cells from rats were exposed to 0.01-10.00MUM roxarsone, 5ng/mL
      vascular endothelial growth factor (VEGF) as a positive control or phosphate
      buffer saline (PBS) as a negative control. Cell proliferation was measured by MTT
      assay, and the content of VEGF in supernatants was measured by enzyme-linked
      immunosorbent assay and Western blotting. A Matrigel-induced tube formation assay
      was used to evaluate the effects of roxarsone on endothelial cells. Additionally,
      the total number and length of microvessels sprouted from rat aortic rings were
      measured for ex vivo investigation of angiogenesis. Results showed that the cell
      viability and total number and length of capillary-like tube formations after
      roxarsone treatment was significantly higher than that of negative (P<0.05), with
      a maximum effect at 1.00MUM exposure. Furthermore, the number of microvessels
      sprouted from aortic rings treated for 4h with 0.1-10.0MUM roxarsone was
      significantly higher than that of PBS treatment, with a peak value of 1.0MUM.
      These results further demonstrate the potential of roxarsone to promote
      angiogenesis in vitro and ex vivo. 

PMID- 24035938
TI  - Angiotensin converting enzyme (ACE) gene expression in experimentally induced
      liver cirrhosis in rats.
AB  - Angiotensin converting enzyme (ACE) is a key player of Renin Angiotensin System
      (RAS), involved in conversion of active product, angiotensin-II. Alterations in
      RAS have been implicated in the pathophysiology of various diseases involving
      heart, kidney, lung and liver. This study is designed to investigate the
      association of ACE gene expression in induction of liver cirrhosis in rats. Total
      12 male albino Wistar rats were selected and divided in two groups. Control group
      received 0.9% NaCl, where as Test group received thioacidamide (TAA), dissolved
      in 0.9%NaCl, injected intraperitoneally at a dosage of 200mg/Kg of body weight,
      twice a week for 12 weeks. The rats were decapitated and blood sample was
      collected at the end of experimental period and used for liver functions, enzyme
      activity, antioxidant enzymes and lipid peroxidation estimations. Genomic DNA was
      isolated from excised tissue determine the ACE genotypes using specific primers.
      The ACE gene expression in liver tissue was assessed using the quantitative RT
      PCR method. The activity of ALT, total and direct bilirubin, SOD and CAT levels
      were significantly high (p<0.05) and level of MDA was significantly low (p<0.05)
      in TAA treated rats as compared to control rats. The ACE gene expression after 12
      weeks TAA treatment in cirrhotic rats was significantly increased (p<0.05) in
      comparison to controls. This study describes the importance of RAS in the
      development of hepatic fibrosis and the benefits of modulation of this system ACE
      gene expression. The finding of major up-regulation of ACE in the experimental
      rat liver provides further insight into the complexities of the RAS and its
      regulation in liver injury. The development of specific modulators of ACE
      activity and function, in future, will help determine the role of ACE and its
      genetic variants in the pathophysiology of liver disease.

PMID- 24035939
TI  - Effects of Allium sativum (garlic) on systolic and diastolic blood pressure in
      patients with essential hypertension.
AB  - The present study evaluated the effects of garlic on blood pressure in patients
      with essential hypertension. Patients (n=210) with stage 1 essential hypertension
      were divided into 7 groups named as A, B, C, D, E, F and G. Each group comprised
      of 30 patients. Each patient in group A, B, C, D and E has received garlic
      tablets at the dose of 300/mg. 600/mg, 900/mg, 1200/mg and 1500/mg in divided
      doses per day respectively for 24 weeks while Group F & group G were given tablet
      atenolol and placebo respectively. Blood pressure readings were recorded at weeks
      0, 12 and 24. Present study showed significant decrease in both Systolic and
      Diastolic blood pressure in both dose and duration dependent manner. In each
      garlic treated group, significant reduction in SBP and DBP (p<0.005) were
      observed when compared with atenolol (P<0.005) and placebo. 

PMID- 24035940
TI  - Chromatographic methods for simultaneous determination of diiodohydroxyquinoline
      and metronidazole in their binary mixture.
AB  - Two chromatographic methods were developed for analysis ofdiiodohydroxyquinoline
      (DIHQ) and metronidazole (MTN). In the first method, diiodohydroxyquinoline and
      metronidazole were separated on TLC silica gel 60F254 plate using chloroform:
      acetone: glacial acetic acid (7.5: 2.5: 0.1, by volume) as mobile phase. The
      obtained bands were then scanned at 254 nm. The second method is a RP-HPLC method
      in which diiodohydroxyquinoline and metronidazole were separated on a reversed
      phase C18 column using water : methanol (60 :40, V/V, PH=3.6 )as mobile phase at
      a flow rate of 0.7 mL.min-1 and UV detection at 220 nm. The mentioned methods
      were successfully used for determination of diiodohydroxyquinoline and
      metronidazole in pure form and in their pharmaceutical formulation.

PMID- 24035941
TI  - Localization of sulphonylurea receptor proteins SUR2A and SUR2B and/or SUR1 in
      rat kidney.
AB  - To further explore precise expression and localization of sulphonylurea receptor
      isoforms SUR2A and SUR2B (SUR1) in rat kidney, total RNA was isolated from the
      kidney tissue using the TRIzol kit. Three different primer sets designed against
      SUR isoforms were used in reverse transcriptase reactions. Western blotting was
      done on membrane fractions obtained from kidney tissues using the primary
      antisera for SUR2A and SUR2B (SUR1). Paraformaldehyde fixed kidney sections were
      immunostained with SUR2A and SUR2B (SUR1) primary antisera. Sections were
      developed with DAB as a chromogen. RT-PCR results demonstrated mRNA consistent
      with SUR1 isoform to be the only identifiable transcript. Western blotting could
      not identify any protein consistent with SUR2A or SUR2B (SUR1) but recognized
      instead a smaller 55kD protein of unknown identity. Immunohistochemistry
      demonstrated a differential staining pattern whereby SUR2A was localized to the
      mesangial cells, intra- and extrarenal blood vessels and smooth muscles. In
      contrast, SUR2B (SUR1) was localized only to distal nephron epithelia. Intense
      immunoreactivity was localized to the thick ascending limb and as well as in the
      outer and inner medullary collecting ducts, both. Our results demonstrate
      differential and highly localized expression pattern of sulphonylurea receptor
      proteins SUR2A and 2B (SUR1) in rat kidney with implications for drug design. 

PMID- 24035942
TI  - Anti-tumor potential and acute toxicity of Jacaranda puberula Cham.
      (Bignoniacea).
AB  - Cancer chemotherapy is an important strategy to treat this leading cause of death
      worldwide and plants may constitute a source of new antineoplastic agents. This
      work fractionated the ethanolic extract of Jacaranda puberula leaves and studied
      the in vitro antitumoral action and some toxicological effects of the most
      bioactive fraction. Cell lines related to worldwide cancers were used. The
      Dichloromethane (DCM) and PP fractions were the most bioactive ones. The anti
      tumoral action of the DCM fraction was higher than that of the crude EtOH extract
      while that of PP fraction was higher than the original one (DCM) for both breast
      (MCF-7), prostate (PC3) and lung (A549) tumor cells, chronic leukemia cells. The
      K562 cells were the most sensitive cell line. The PP fraction (20 MUg/mL)
      cytotoxicity for these cells was similar to that of the ursolic acid triterpene
      or the antineoplastic ethoposide. The PP fraction inhibited K562 cell
      proliferation without cell cycle arrest in a specific phase or apoptosis. PP
      increased the mitochondrial reduction activity of lymphocytes. After a single
      dose by oral route, PP fraction did not induce intrinsic acute toxicity or animal
      death. This work demonstrated that the J. puberula fraction (PP) present high in
      vitro anti-tumoral effect with no cytotoxicity for immune system cells or oral
      acute toxicity, improving the Jacaranda puberula ethnopharmacology and reporting
      new biological effects for the genus Jacaranda. 

PMID- 24035943
TI  - Preliminary evaluation of antimicrobial activity of cream formulated with
      essential oil of Trachyuspermum ammi.
AB  - In our present research we studied physiochemical properties and antimicrobial
      activity of T. ammi (Trachyuspermum ammi) seeds. The seeds yielded 2.86%
      essential oil. Refractive index, specific gravity, acid value, and easter values
      were 1.496, 0.9212, 1.12 and 2.80 respectively. GLC was used to determine the
      composition of oil. The major component of oil was Thymol (55.308%).
      Antimicrobial activity of the oil was carried out against four species of
      bacteria and fungs. The oil was used to formulate a cream and the pH,
      physiochemical stability, phase separation and dermal irritation of cream were
      investigated. The cream was examined for healing wound in rabbits in comparison
      with Iodine tincture. 

PMID- 24035944
TI  - Inhibitory and bactericidal activity of selected South African honeys and their
      solvent extracts against clinical isolates of Helicobacter pylori.
AB  - The growing problem of antibiotic resistance by Helicobacter pylori demands the
      search for novel compounds, especially from natural sources. We evaluated the
      anti-H. pylori activity of six local honeys at different concentrations as well
      as their solvent extracts by the Hole Plate diffusion method. The minimum
      inhibitory concentration (MIC50) of the two most active extracts of each honey
      was determined by the broth microdilution method; and the time kill assay of the
      most active extract of each honey determined by viability studies. Data were
      analyzed by one-way ANOVA test at 95% significance level. All the honey varieties
      as well as their solvent extracts demonstrated varying levels of antibacterial
      activity based on different mean zone diameters [16.0mm (crude) to 22.2mm
      (extract)] and percentage susceptibilities [73.3% (crude) to 93.3% (extract)] of
      the test isolates. The chloroform extracts of Pure Honey (PH) and Champagne Royal
      Train (CRT) recorded MIC50 ranges of 0.01-10% and 0.625-10 % (v/v) respectively;
      that were not significantly different (P > 0.05) from amoxicillin (0.001
      1.25mg/mL), the positive control. The most potent bactericidal effect against the
      test isolates was obtained with 5% v/v (1/2 MIC) concentration of chloroform
      extract of PH from 42-72 hrs. In conclusion, these honeys and their extracts
      could be leads for further investigation in the discovery of new natural anti-H.
      pylori compounds.

PMID- 24035945
TI  - Carboxypeptidase-B from Bubalus bubalis pancreas: purification, properties and
      MALDI-TOF monitored activation of proinsulin.
AB  - Carboxypeptidase-B (E.C 3.4.17.2) catalyzes the hydrolysis of peptides and esters
      at C-terminus of arginine and lysine residues. Our study describes the large
      scale purification, N-terminal sequence analysis and physiochemical properties of
      pancreatic enzyme from river buffalo (Bubalus bubalis). The enzyme was purified
      up to 71 folds by anion-exchange chromatography with 21% final recovery. Purified
      enzyme displayed two bands on SDS-PAGE with molecular weights of 9 kDa and 26 kDa
      respectively, the N-terminal sequence of later was EFLDKLDFYV. The enzyme has
      shown optimum activity at pH 9.0 and 40?C. The KM, Kcat and Kcat/KM values of
      purified carboxypeptidase-B with Hippuryl-L-Arg are 30MUM, 72sec(-1) and
      2.4x10(5) M(-1) sec(-1) respectively. A computer based model for the structure of
      enzyme was proposed by chromatographic studies of component fragments and N
      terminal sequence. The enzyme purified in the present study was free of
      carboxypeptidase A and endoprotease contamination. It was efficiently used in the
      processing of recombinant buffalo proinsulin, in combination with trypsin.
      Activation of proinsulin was monitored by MALDI-TOF analysis of peptides before
      and after the action of enzymes. 

PMID- 24035946
TI  - Effects of propolis on blood biochemical and hematological parameters in nitric
      oxide synthase inhibited rats by Nomega-Nitro-L-arginine methyl ester.
AB  - This study showed the effects of propolis on biochemical and hematological
      parameters in chronic nitric oxide synthase inhibited rats by Nomega-Nitro-L
      arginine methyl ester (L-NAME). Rats are given L-NAME for 15 days and the
      propolis for the last 5 days with L-NAME together. The levels of aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma
      glutamyltransferase in the L-NAME group compared to control group have increased
      (P<0.05). The levels of these parameters in L-NAME+propolis group compared to the
      L-NAME group have decreased (P<0.05). L-NAME caused increase (P<0.05) in levels
      of glucose, albumin, globulin, creatinine, urea, triglyceride and cholesterol.
      Erythrocyte number, total leukocyte, hemoglobin, hematocrit, neutrophil and
      monocyte decreased (P<0.05), platelets and lymphocyte increased (P<0.05) in L
      NAME+propolis group compared to the L-NAME group. The study concluded that
      homeostasis is modulated in L-NAME administrated rats by adding propolis which
      causes increasing generation of vascular nitric oxide. 

PMID- 24035947
TI  - Validated spectrofluorimetric method for determination of sulpiride in commercial
      formulations using Hantzsch condensation reaction.
AB  - A simple, sensitive, selective and cost effective spectrofluorimetric method has
      been established for the quantification of sulpiride after their complete
      alkaline hydrolysis. The method is based on the condensation of the primary amino
      group of alkaline hydrolytic product of sulpiride with acetyl acetone and
      formaldehyde in acidic medium (0.25 M HCl) to form a fluorescent product. The
      reaction product formed shows maximum fluorescence intensity at 483 nm after
      excitation at 431 nm. The different reaction conditions influencing the
      condensation reaction were carefully optimized and a linear range of 0.1-3.5 ug
      mL-1 with good correlation coefficient between flourescent intensity and
      concentration of sulpiride was found at optimum parameters. The LOD and LOQ were
      found to be 11 and 39 ng mL-1 respectively. The proposed method was successfully
      used for the quantification of sulpiride in bulk powder and commercial
      formulations. The effect of common pharmaceutical excipients and co-administered
      drug was also studied and no interferences were observed. The validity of the
      method was tested by analyzing sulpiride in bulk powder, and pharmaceutical
      formulations through recovery studies. Recoveries (%) were obtained from 98.62 to
      100.24% for bulk powder, and 97.09 to 100.57 % for commercial formulations. The
      results were validated statistically with those obtained by reference literature
      high performance liquid chromatographic method.

PMID- 24035948
TI  - Optimization of sustained release matrix tablet of metoprolol succinate using
      central composite design.
AB  - The present study was performed to optimize the formulation of metoprolol
      succinate (MS) sustained release tablets using hydroxypropyl methylcellulose
      (HPMC) and sodium alginate (SA) as the matrix combination. After investigating
      the effects of various parameters on drug release, a 2-factor, 5-level central
      composite design was employed, using the amount of HPMC K4M (A) and SA (318 cP)
      (B) as the independent variables and the drug percentage released at 1h, 4h, 8h,
      20h (Q1, Q4, Q8, Q20) as the responses. Response surfaces were established to
      obtain the matrix ranges and the main factors affecting four responses. In order
      to validate the optimization study, six confirmatory runs were performed;
      indicating high predictability of response surface methodology for MS sustained
      release tablets. Data fitting to Peppas equation indicated that the mechanism of
      drug release could be diffusion along with erosion. This matrix combination can
      be used as a good alternative to the commercially pellet technology, which was
      complicated, time-consuming and energy-intensive. 

PMID- 24035949
TI  - Effects of rocuronium pretreatment on muscle enzyme levels following
      succinylcholine.
AB  - Succinylcholine revolutionized anaesthetic practice by providing intense
      neuromuscular blockade of very rapid onset and ultrashort duration, thereby
      greatly easing the maneuver of tracheal intubation. However the worth of
      succinylcholine is limited by the frequent occurrence of muscular side effects
      which manifest biochemically in the form of rise in serum creatine kinase (CK).
      The administration of small doses of nondepolarizing muscle relaxants before the
      administration of succinylcholine has been shown to decrease the incidence and
      severity of muscular side effects experienced by the patients. This study was
      aimed at evaluating the efficacy of technique in reducing the muscular side
      effects of succinylcholine, biochemically manifested as rise in CK. Sixty healthy
      adults were enrolled in the study who were scheduled for minor muscle cutting
      surgeries under general anaesthesia. They were assigned at random to two groups
      of thirty patients each. They randomly received succinylcholine for intubation
      and a precurarization dose of rocuronium followed by succinylcholine for
      intubation. Blood samples were drawn for estimation of serum creatinine kinase.
      There was a significantly raised CK in the succinylcholine group. In the
      precurarization group the rise in CK was prevented and the levels were
      significantly less as compared to the group which received succinylcholine alone.
      Present study concluded that precurarization with rocuronium was effective in
      reducing the succinylcholine-induced rise in creatinine kinase. 

PMID- 24035950
TI  - Levan as a new additive for colon-specific films: a new approach in the use of
      exopolysaccharides in time-dependent free films (Aminoalkyl Methacrylate
      Copolymer RS).
AB  - Time-dependent films, augmented with prebiotics, offer potential strategy for
      colon-specific controlled drug release. In this study, we produced films
      containing levan (L) and Aminoalkyl Methacrylate Copolymer RS (ER). Free films of
      ER combined with levan were produced by the casting process and characterized by
      the mobility of the polymeric matrix, hydration, differential scanning
      calorimetry (DSC) and thermogravimetry (TGA). The results of this study suggest
      that the exopolysaccharide levan can be used in combination with ER for colon
      specific materials. No evidence of incompatibilities between the levan and the
      synthetic polymer were detected, and levan improved the mobility of the polymeric
      matrix and the hydrophilicity of the system. Levan may have positively altered
      the density of the polymeric matrix, as visualized by thermal characterization.
      The endothermic decomposition peak was shifted with increasing amounts of levan.
      This new barrier polymer utilized a combination of time-dependent enzymatic
      mechanisms and can be considered promising for use in the coating of solid oral
      drugs for specific release. 

PMID- 24035951
TI  - In vitro antioxidant activities of four medicinal plants on the basis of DPPH
      free radical scavenging.
AB  - The present research investigation was aimed at the evaluation of antioxidant
      activities of methanolic (70%) extracts of whole plant of Pentanema vestitum and
      fruits of Pistacia integerrima, Withiana somniferra and Withiana coagulans on
      scavenging of 2, 2-diphenyl-2-picrylhydrazyl (DPPH) free radical. The rank of
      order of free antioxidant activity of the selected plants was; P. integerrima >
      P. vestitum > W. somniferra > W. coagulans as compared to standard Ascorbic acid.
      P. integerrima showed significantly higher activity at all concentrations as
      compared to Ascorbic acid at P<0.05. The percent inhibition caused by P.
      integerrima at lowest concentration (40 ppm) was 68.16+/-0.5 and that of Ascorbic
      acid was 62.00+/-0.5. The IC50 value of P. integerrima was 5.75ppm as compared to
      ascorbic acid having 15.09 ppm. The percent inhibition at all concentrations
      caused by P. vestitum was not significantly different from Ascorbic acid at
      P<0.05. The IC50 value of P. vestitum was 13.00ppm and that of Ascorbic acid was
      15.09 ppm. The percent inhibitions caused by W. somniferra (IC50=46.85 ppm) and
      W. coagulans (IC50=84.40 ppm) were most significantly lower than Ascorbic acid at
      P<0.05. It is inferred from the current study that the methanolic (70%) extracts
      of the P. integerrima and P. vestitum could be used in preparation of potent
      antioxidant drugs.

PMID- 24035952
TI  - Appraisal of multifarious brands of Cephradine for their in vitro antibacterial
      activity against varied microorganisms.
AB  - The astounding and exceptional growth of generic pharmaceutical Industry in
      Pakistan has raised certain questions for drug regulatory authorities
      contemplating their efficacy and quality. The current study focuses on assessing
      the in-vitro antimicrobial activity of 24 brands of Cephradine 500mg capsules
      against 4 different strains by employing standardized methods. Disk diffusion
      method was performed on all brands to look into the susceptibility and resistance
      patterns. Standard disk of 5ug Cephradine powder were used during evaluation. The
      zones of inhibitions were ranged from 24-40mm against S. aureus, 24-40mm against
      E. coli, 20-25mm against K. pneumonia and 19-23mm P. mirabilis. On the basis of
      mean value, the multinational brands were found to have better zone of
      inhibitions and were better than local Pharmaceutical companies but ANOVA
      cooperative study showed that all brands of Cephradine showed similar comparable
      results. Further investigations by employing MIC method, quality of raw material
      with special emphasis on the shelf-life, excepients and method of manufacturing
      will be needed to obtain more authenticated results. The price of National and
      Multinational brands ranges from Rs.156.00-212.00 for 10 capsules. It is
      concluded that Public health is at risk because of noticeable growing widespread
      curse of the manufacture and trade of sub-standard or below par pharmaceuticals.
      The pecuniary accountability of management of pharmaceutical agents is
      additionally apparent. The results of the study need to be made public to boost
      the confidence of medical profession about the quality of locally manufactured
      pharmaceuticals. It will succour the foreign exchange being incurred on the trade
      in of medicines.

PMID- 24035953
TI  - RP-HPLC analytical method development and optimization for quantification of
      donepezil hydrochloride in orally disintegrating tablet.
AB  - An easy, fast and validated RV-HPLC method was invented to quantify donepezil
      hydrochloride in drug solution and orally disintegrating tablet. The separation
      was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with
      UV detection at 268 nm. Method optimization was tested using various composition
      of organic solvent. The mobile phase comprised of phosphate buffer (0.01M),
      methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid
      (80%) was found as the optimum mobile phase. The method showed intraday precision
      and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively,
      while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to
      1.90% respectively. The standard calibration curve was linear from 0.125 MUg/mL
      to 16 MUg/mL, with correlation coefficient of 0.9997+/-0.00016. The drug solution
      was stable under room temperature at least for 6 hours. System suitability
      studies were done. The average plate count was > 2000, tailing factor <1, and
      capacity factor of 3.30. The retention time was 5.6 min. The HPLC method was used
      to assay donepezil hydrochloride in tablet and dissolution study of in-house
      manufactured donepezil orally disintegrating tablet and original Aricept. 

PMID- 24035954
TI  - Assessment of total phenolic content and antioxidant potential of methanol
      extract of Peltophorum pterocarpum (DC.) Backer ex K. Heyne.
AB  - Plants are rich in a variety of chemical compounds. Many are secondary
      metabolites including aromatic substances most of them are phenols or their
      oxygen substituted derivatives. Medicinal plants are rich in antioxidant
      constituents such as phenols, tocopherols, ascorbic acid, carotenoids, and
      flavonoids etc. They are found to acquire free radical scavenging activity and
      used worldwide for the treatment of various immune system dependent diseases.
      Peltophorum pterocarpum (DC) Backer ex K. Heyne (Caesalpiniaceae) is a beautiful
      ornamental tree, widely grown in tropical regions and its parts are used in
      traditional medicine as medicinal agents. Fresh pods of Peltophorum pterocarpum
      was evaluated for its antioxidant potential by using various methods including
      DPPH, superoxide anion, nitric oxide scavenging, and metal chelating activity.
      TPC via Folin-Ciocalteau's reagent and anti haemolytic activity red blood cells
      respectively have also been measured. The methanol extract of pods of Peltophorum
      pterocarpum was found to possess the significant amount 439.21+/-0.17 mg GAE
      (gallic acid equivalents) / g of TPC. The antioxidant potential of pods extract
      at mature stage showed potent activity and measured as, free radical scavenging
      activity 73.29+/-0.81%, superoxide anion scavenging activity 89.03+/-1.07%,
      nitric oxide scavenging activity 84.25+/-1.18%, and metal chelating activity
      64.12+/-0.11%. The extract also showed potent anti haemolytic activity 79.09+/-
      0.75%. Peltophorum pterocarpum exhibited strong but varying level of antioxidant
      and anti haemolytic activity in various methods along with total phenolic
      contents. 

PMID- 24035955
TI  - Comparative evaluation of the anti-diabetic activity of Pterocarpus marsupium
      Roxb. heartwood in alloxan induced diabetic rats using extracts obtained by
      optimized conventional and non conventional extraction methods.
AB  - The aim of the present study was to assess the anti-diabetic activity of
      Pterocarpus marsupium Roxb. heartwood in alloxan induced diabetic rats using
      extracts obtained by optimized conventional and non conventional extraction
      methods. Aqueous and ethanol extracts of Pterocarpus marsupium heartwood were
      prepared by conventional methods (infusion, decoction, maceration and
      percolation) and non conventional methods, such as ultrasound-assisted extraction
      (UAE) and microwave-assisted extraction (MAE). The crude aqueous extracts were
      administered orally to both normal and alloxan induced male albino rats (Sprague
      Dawley strain). The experimental set up consisted of 48 male albino rats divided
      into 6 groups: Normal control, diabetic control (sterile normal saline, 1 ml/100
      g body weight), standard (gliclazide, 25 mg/1000g of body weight), groups 4-6
      (crude aqueous percolation, optimized UAE and MAE extract, 250 mg/1000g of body
      weight). In acute treatment, the reduction of blood glucose level was
      statistically significant with the oral administration of UAE and percolation
      aqueous extracts to the hyperglycemic rats. In sub-acute treatment, the UAE
      aqueous extract led to consistent and statistically significant (p<0.001)
      reduction in the blood glucose levels. There was no abnormal change in body
      weight of the hyperglycemic animals after 10 days of administration of plant
      extracts and gliclazide. This study justifies the traditional claim and provides
      a rationale for the use of Pterocarpus marsupium to treat diabetes mellitus. The
      antidiabetic activity of Pterocarpus marsupium can be enhanced by extracting the
      heartwood by non conventional method of UAE. 

PMID- 24035956
TI  - Electro-analysis of the drugs in solid dosage form at platinum and gold
      electrodes.
AB  - Voltammetric analysis at platinum and gold rotating disc electrode (RDE) in 0.1
      mol l(-1) sulphuric acid has been applied for the determination of the active
      ingredient in solid dosage form. Non zero intercept in the limiting current
      versus concentration plot was proportionally good to excellent for the solid
      dosage form and is free from interference from adsorption on the electrodes. All
      of the dosage forms proved amenable to rapid voltammetric determination with a
      means standard deviation of 1.2. 

PMID- 24035957
TI  - The effects of gabapentin on methadone based addiction treatment: a randomized
      controlled trial.
AB  - Gabapentin is a potentially useful drug in alleviating the hyperexcitatory
      painful states in the control of opiate dependence in acute detoxification and
      the stabilization phase. This study aim was to evaluate the effectiveness of
      gabapentin adds-on methadone therapy on lowering the methadone. This randomized
      double blind controlled clinical trial conducted at an outpatient rehabilitation
      clinic. Sixty patients using opium, opium extract and heroin were randomly
      assigned to two groups (34 in treatment group and 26 in control group); one group
      was prescribed combination of methadone (40-120 mg) and gabapentin (300 mg) as
      group A, and the other group was given methadone (40-120) and placebo as group B.
      The subjects were followed up for three weeks after intervention. There were 60
      outpatients including 51 males with the mean age of 40.9+/-9.2. Daily dose and
      cumulative dose of methadone during the treatment was found to be significantly
      higher in group B (73.8+/-19.5 mg daily vs. 58.9+/-11 mg daily and cumulatively
      1550.7+/-409.7 mg vs. 238.3+/-238.2 mg, p= 0.001). When the patients were
      stratified based on the kind of abused drug, the methadone dose was seen to be
      significantly reduced in the opium addicted patients in the group A. Group A
      showed more withdrawal symptoms whereas the most common complain of group B was
      sedation particularly during the first three days. The results showed that
      gabapentin is an effective adds-on therapy when is added to methadone. This drug
      leads to relief of withdrawal symptoms and lower methadone consumption. 

PMID- 24035958
TI  - Efficacy of herbal coded Hepcon on drug induced hepatitis in experimental animals
      through histopathological and biochemical analysis.
AB  - Drug-induced liver injury is the leading cause for more than 50 percent of cases
      of acute liver failure. This study was conducted on herbo-mineral formulation
      "Hepcon" to evaluate its hepatoprotective effects in drug induced hepatitis in
      experimental animals. The liver injury was introduced with over dosage of non
      steroidal anti-inflammatory drugs (NSAIDs) and carbon tetrachloride (CCl4). The
      herbo-mineral formulations "Hepcon" consist of Zingiber officinale, Piprum
      nigrum, Ammonium chloride and Arsenic trioxide (Hartal warqi). The aqueous
      extraction was administered to experimental animals. Thereafter their LFTs, IgG,
      and tissue pathology was studied. It was observed on the basis of biochemical and
      histopathological analysis that animals which were subjected to Hepcon became
      normal in 60 days whereas those as control group did not showed improvements and
      most of them died. It was concluded that the efficacy of Hepcon to treat liver
      injury caused by CCl4 and NSAIDs is very effective, and no side effects were
      noticed.

PMID- 24035959
TI  - Study of the hepatoprotective effect of Juniperus phoenicea constituents.
AB  - Different fraction obtained from the aerial parts of Juniperus phoenicea showed
      significant activity as hepatoprotective when investigated against carbon
      tetrachloride induced liver injury. The hepatoprotective activity was evaluated
      through the quantification of biochemical parameters and confirmed using
      histopathology study. Phytochemical investigation of the petroleum ether,
      chloroform and methanol fractions utilizing different chromatographic techniques
      resulted in the isolation of five known diterpenoids namely: 13-epicupressic acid
      (1), imbricatolic acid (2), 7alpha-hydroxysandaracopimaric acid (3), 3beta
      hydroxysandaracopimaric acid (4), isopimaric acid (5), four flavonoid
      derivatives: cupressuflavone (6), hinokiflavone (7), hypolaetin-7-O-beta
      xylopyranoside (9), (-) catechin (10), inaddition to sucrose (8). Both physical
      and spectral data were used for structure determination and all isolates were
      evaluated for their hepatoprotective activity. Compounds 2 and 6 were effective,
      however; 7 was the most active. Hepatoprotective activity of 7 is comparable with
      the standard drug silymarin in reducing the elevated liver enzymes and restoring
      normal appearance of hepatocytes. Hepatoprotective effect of combination of 6, 7
      and silymarin with the diterpene sugiol was also explored.

PMID- 24035960
TI  - Anticancer investigations on Carissa opaca and Toona ciliata extracts against
      human breast carcinoma cell line.
AB  - This study was aimed to determine the effectiveness of two ethnobotanically
      important plant species Carissa opaca and Toona ciliata against cancer cells.
      Antiproliferative activity of the plant extracts and their fractions was tested
      against MCF-7 breast cancer cell line using MTT assay. A concentration dependent
      inhibition was observed for both crude extracts. C. opaca crude extract showed
      78.5% inhibition while T. ciliata showed 57% activity against cancer cells at 500
      MUg/mL. Fractions were tested at 200 MUg/mL concentration and were more active
      than crude extracts. Chloroform fraction of C. opaca showed maximum inhibition
      99% followed by ethyl acetate and methanol fraction of C. opaca exhibiting 96%
      and 94% inhibition, respectively. Ethyl acetate fraction of T. ciliata showed 78%
      inhibition of cancer cells at the same concentration. Preliminary phytochemical
      screening revealed the chemical composition of C. opaca extract containing
      alkaloids, flavonoids, tannins and saponins while T. ciliata had tannins and
      coumarins. Present investigation suggests that tested plant species possess
      potent anticancer compounds specially chloroform, ethyl acetate and methanol
      fractions of C. opaca and ethyl acetate fraction of T. ciliata can be an
      important source of anticancer drugs. 

PMID- 24035962
TI  - Selective extraction of berberine and palmatine from Huangbai powder.
AB  - Berberine and palmatine are two of the main bioactive components in Huangbai, a
      major Chinese medicinal herb. The current methods to extract these compounds
      usually involving the usage of inorganic acid and base, are not only complex and
      time-consuming, but have a low selectivity. In this paper, it was reported that
      hexane, ethyl acetate and dichloromethane were tested to extract berberine and
      palmatine from Huangbai powder. The results showed that dichloromethane extracted
      selectively and effectively berberine and palmatine from Huangbai powder among
      the examined solvents. In addition, dichloromethane can be recycled and reused,
      making it a potential candidate for large scale extraction of berberine and
      palmatine from Huangbai. 

PMID- 24035961
TI  - Comparative cardiac toxicity in two treatment schedules of 5-FU/LV for colorectal
      carcinoma.
AB  - The purpose of the study is evaluation and assessment of parameters of cardiac
      toxicity in patients subjected to 5-FU based chemotherapy. Cardiac morbidity is a
      reported outcome in different 5FU/LV regimens; however none of them are definite
      or proximate. The bimonthly regimen of high dose leucovorin is reported to be
      less toxic and more effective as compared to the monthly regimen of low dose
      leucovorin. We report the detailed assessment of few cardiac parameter of
      toxicity in patients of advanced colorectal carcinoma subjected to two Schedules
      of high and low dose Folinic Acid, 5-Fluorouracil, bolus and continuous infusion.
      The correlation of elevated cardiac biomarkers, angina and hypertension is
      comparatively assessed in patients with normal general status, hyperglycemia and
      known cardiac disorders subjected to two different 5FU based chemotherapeutic
      regimen. 

PMID- 24035963
TI  - The effects of Cosmos caudatus (Ulam Raja) supplementation on bone biochemical
      parameters in ovariectomized rats.
AB  - Cosmos caudatus (ulam raja) contains high mineral content and possesses high
      antioxidant activity which may be beneficial in bone disorder such as
      postmenopausal osteoporosis. The effects of C. caudatus on bone metabolism
      biomarkers in ovariectomized rats were studied. 48 Sprague-Dawley rats aged three
      months were divided into 6 groups. One group of rats was sham-operated while the
      remaining rats were ovariectomized. The ovariectomized rats were further divided
      into 5 groups: the control, three groups force-fed with C. caudatus at the doses
      of 100mg/kg, 200mg/kg or 300mg/kg and another group supplemented with calcium 1%
      ad libitum. Treatments were given 6 days per week for a period of eight weeks.
      Blood samples were collected twice; before and after treatment. Parameters
      measured were bone resorbing cytokine; interleukin-1 and the bone biomarkers;
      osteocalcin and pyridinoline. Serum IL-1 and pyridinoline levels were
      significantly increased in ovariectomized rats. Supplementation of C. caudatus
      was able to prevent the increase of IL-1 and pyridinoline in ovariectomized rats.
      Besides that, C. caudatus showed the same effect as calcium 1% on biochemical
      parameters of bone metabolism in ovariectomized rats. In conclusion, Cosmos
      caudatus was as effective as calcium in preventing the increase in bone
      resorption in ovariectomized rats. 

PMID- 24035964
TI  - Evaluation of various concentrations of alkaline surface treatment on interfacial
      bond strengths of amalgam bonded to amalgam.
AB  - This study was done to assess the influence of alkaline surface modification on
      interfacial bond strength of existing fractured (old) amalgam restoration bonded
      to fresh amalgam. Old and Fresh amalgam interfaced samples were prepared by
      applying a 4-methacryloyloxyethy trimellitate anhydride (4-META) containing
      adhesive. The adhesive used was Amalgabond (Parkell, Farmingdale, NY 11735, USA).
      Four concentrations of calcium hydroxide Ca(OH)2 solutions were used as a surface
      modifiers for old amalgam to increase the pH of the amalgam surfaces. The
      concentrations used were 2.5, 5, 10 and 15%. Direct measurement of the
      interfacial bond strength was carried out using an electromechanical universal
      tensile testing machine at crosshead speed of 10mm per minute. Results show that
      all the calcium hydroxide modified samples produced the increased tensile bond
      strength (TBS) as compared to their control group. The highest values of bond
      strength were achieved using 15% Ca(OH)2 solution as surface modifier.
      Pretreatment of fractured amalgam with calcium hydroxide improves the bond
      strength of 4-META adhesives. Its use in repair of amalgam may therefore be
      considered. 

PMID- 24035965
TI  - In vitro evaluation of vincristine and fluconazole combination against Candida.
AB  - Infections associated with cancer are a major scourge and cause of substantial
      morbidity and mortality in cancer patients. The aim of present study was to
      appraise the in vitro activity of anticancer agent vincristine and antifungal
      fluconazole alone and in combination against Candida spp. Results were
      interpreted in terms of fractional inhibitory concentration index (FICI).
      Antifungal activity of fluconazole showed marked synergism when used in
      combination with vincristine, with FICI ranging from 0.25-0.5 against different
      Candida spp. Although, the use of vincristine with fluconazole is always disputed
      due to its side effects including decreased peristalsis, but the present research
      can help to perform suitability analysis of fluconazole use in life threatening
      invasive candidiasis associated with cancer patients. In addition, the synergism
      in antifungal activity after using with vincristine also warrants further
      research in the direction of minimizing adverse reaction associated with combined
      use of fluconazole and vincristine. 

PMID- 24035966
TI  - In vitro synergistic effect of ciprofloxacin with aminoglycosides against
      multidrug resistant-Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an increasingly prevalent nosocomial human pathogen.
      Infections with multidrug-resistant (MDR) P. aeruginosa are currently a treatment
      challenge and requires search for better treatment options. PURPOSE OF STUDY: To
      determine in vitro synergistic effect of ciprofloxacin in combination with
      amikacin and gentamicin against MDR P. aeruginosa clinical isolates. METHODS:
      Antibiotic resistance pattern of 100 identified clinical isolates of P.
      aeruginosa was determined against eight antibiotics by disc diffusion method at
      Microbiology Laboratory, Holy Family Hospital, Rawalpindi. For 30 selected MDR
      isolates, minimum inhibitory concentrations (MICs) of amikacin and gentamicin
      were determined separately by agar diffusion method followed by combined activity
      of ciprofloxacin with amikacin and gentamicin by checkerboard agar dilution
      technique. RESULTS: Antibiotic resistance pattern of P. aeruginosa isolates was;
      gentamicin and carbenicillin (94%), amikacin and piperacillin (92%), ceftazidime
      (90%), colistin (87%), ciprofloxacin (79%) and imipenem (72%). MICs against 30
      selected MDR isolates ranged from 32 to >128MUg/mL for amikacin, and >128MUg/mL
      for gentamicin. Synergistic effect was observed in 12/30(40%) isolates for AK+CIP
      and in 05/30 (16.7%) for CN+CIP. CONCLUSION: Ciprofloxacin in combination with
      amikacin and gentamicin showed synergistic effect and no antagonistic effect
      against MDR P. aeruginosa.

PMID- 24035967
TI  - Oritavancin - a new semisynthetic lipoglycopeptide agent to tackle the challenge
      of resistant gram positive pathogens.
AB  - Natural glycopeptide antibiotics like vancomycin and teicoplanin have played a
      significant role in countering the threat posed by Gram-positive bacterial
      infections. The emergence of resistance to glycopeptides among enterococci and
      staphylococci has prompted the search for second-generation drugs of this class
      and semi-synthetic derivatives are currently under clinical trials. Antimicrobial
      resistance among Gram-positive organisms has been increasing steadily during the
      past several decades and the current development of antibiotics falls short of
      meeting the needs. Oritavancin (LY-333328 diphosphate), a promising novel second
      generation semisynthetic lipoglycopeptide, has a mechanism of action similar to
      that of other glycopeptides. It has concentration-dependent activity against a
      variety of Gram-positive organisms specially methicillin-resistant Staphylococcus
      aureus (MRSA), vancomycin-intermediate resistant Staphylococcus aureus (VISA),
      Streptococcus pneumoniae and vancomycin-resistant enterococcus. It is rapidly
      bactericidal against many species and in particular for enterococci where
      vancomycin and teicoplanin are only bacteriostatic even against susceptible
      strains. The pharmacokinetic profile of oritavancin has not been fully described;
      however, oritavancin has a long half-life of about 195.4 hours and is slowly
      eliminated by renal means. Oritavancin is not metabolized by the liver in
      animals. Oritavancin will most probably be prescribed as a once-daily dose and it
      demonstrates concentration-dependent bactericidal activity. Oritavancin has
      demonstrated preliminary safety and efficacy in Phase I and II clinical trials.
      In a Phase III clinical trial, oritavancin has achieved the primary efficacy end
      point in the treatment of complicated Gram-positive skin and skin-structure
      infections. To date, adverse events have been mild and limited; the most common
      being administration site complaints, headache, rhinitis, dry skin, pain,
      increases in liver transaminases and accumulation of free cholesterol and
      phospholipids in phagocytic (macrophages) and nonphagocytic (fibroblast) cells.
      Oritavancin appears to be a promising antimicrobial alternative to vancomycin
      (with additional activity against Staphylococcus and Enterococcus resistant to
      vancomycin) for the treatment of complicated Gram-positive skin and skin
      structure infections. Additional clinical data are required to fully explore its
      use. 

PMID- 24035968
TI  - Vitamin B6: deficiency diseases and methods of analysis.
AB  - Vitamin B6 (pyridoxine) is closely associated with the functions of the nervous,
      immune and endocrine systems. It also participates in the metabolic processes of
      proteins, lipids and carbohydrates. Pyridoxine deficiency may result in
      neurological disorders including convulsions and epileptic encephalopathy and may
      lead to infant abnormalities. The Intravenous administration of pyridoxine to
      patients results in a dramatic cessation of seizures. A number of analytical
      methods were developed for the determination of pyridoxine in different dosage
      forms, food materials and biological fluids. These include UV spectrometric,
      spectrofluorimetric, mass spectrometric, thin-layer and high-performance liquid
      chromatographic, electrophoretic, electrochemical and enzymatic methods. Most of
      these methods are capable of determining pyridoxine in the presence of other
      vitamins and complex systems in ug quantities. The development and applications
      of these methods in pharmaceutical and clinical analysis mostly during the last
      decade have been reviewed. 

PMID- 24035969
TI  - Transmission of DNA damage and increasing reprotoxic effects over two generations
      of Daphnia magna exposed to uranium.
AB  - This study aimed to examine the mechanisms involved in the transgenerational
      increase in Daphnia magna sensitivity to waterborne depleted uranium (DU) under
      controlled laboratory conditions. Daphnids were exposed to concentrations ranging
      from 2 to 50 MUg L(-1) over two successive generations. Genotoxic effects were
      assessed using random amplified polymorphic DNA and real time PCR (RAPD-PCR).
      Effects on life history (survival, fecundity and somatic growth) were monitored
      from hatching to release of brood 5. Different exposure regimes were tested to
      investigate the specific sensitivity of various life stages to DU. When daphnids
      were exposed continuously or from hatching to deposition of brood 5, results
      demonstrated that DNA damage accumulated in females and were transmitted to
      offspring in parallel with an increase in severity of effects on life history
      across generations. When daphnids were exposed during the embryo stage only, DU
      exposure induced transient DNA damage which was repaired after neonates were
      returned to a clean medium. Effects on life history remained visible after
      hatching and did not significantly increase in severity across generations. The
      present results suggest that DNA damage might be an early indicator of future
      effects on life history.

PMID- 24035970
TI  - The role of metabolomics in neonatal and pediatric laboratory medicine.
AB  - Metabolomics consists of the quantitative analysis of a large number of low
      molecular mass metabolites involving substrates or products in metabolic pathways
      existing in all living systems. The analysis of the metabolic profile detectable
      in a human biological fluid allows to instantly identify changes in the
      composition of endogenous and exogenous metabolites caused by the interaction
      between specific physiopathological states, gene expression, and environment. In
      pediatrics and neonatology, metabolomics offers new encouraging perspectives for
      the improvement of critically ill patient outcome, for the early recognition of
      metabolic profiles associated with the development of diseases in the adult life,
      and for delivery of individualized medicine. In this view, nutrimetabolomics,
      based on the recognition of specific cluster of metabolites associated with
      nutrition and pharmacometabolomics, based on the capacity to personalize drug
      therapy by analyzing metabolic modifications due to therapeutic treatment may
      open new frontiers in the prevention and in the treatment of pediatric and
      neonatal diseases. This review summarizes the most relevant results published in
      the literature on the application of metabolomics in pediatric and neonatal
      clinical settings. However, there is the urgent need to standardize physiological
      and preanalytical variables, analytical methods, data processing, and result
      presentation, before establishing the definitive clinical value of results. 

PMID- 24035971
TI  - Constitutional 11q14-q22 chromosome deletion syndrome in a child with
      neuroblastoma MYCN single copy.
AB  - Constitutional 11q deletion is a chromosome imbalance possibly found in MCA/MR
      patients analyzed for chromosomal anomalies. Its role in determining the
      phenotype depends on extension and position of deleted region. Loss of
      heterozygosity of 11q (region 11q23) is also associated with neuroblastoma, the
      most frequent extra cranial cancer in children. It represents one of the most
      frequent cytogenetic abnormalities observed in the tumor of patients with high
      risk disease even if germline deletion of 11q in neuroblastoma is rare. Hereby,
      we describe a 18 months old girl presenting with trigonocephaly and dysmorphic
      facial features, including hypotelorism, broad depressed nasal bridge,
      micrognathia, synophrys, epicanthal folds, and with a stage 4 neuroblastoma
      without MYCN amplification, carrying a germline 11q deletion (11q14.1-q22.3),
      outside from Jacobsen syndrome and from neuroblastoma 11q critical regions. The
      role of 11q deletion in determining the clinical phenotype and its association
      with neuroblastoma development in the patient are discussed. 

PMID- 24035972
TI  - Zinc ferrite nanoparticles activate IL-1b, NFKB1, CCL21 and NOS2 signaling to
      induce mitochondrial dependent intrinsic apoptotic pathway in WISH cells.
AB  - The present study has demonstrated the translocation of zinc ferrite
      nanoparticles (ZnFe2O4-NPs) into the cytoplasm of human amnion epithelial (WISH)
      cells, and the ensuing cytotoxicity and genetic damage. The results suggested
      that in situ NPs induced oxidative stress, alterations in cellular membrane and
      DNA strand breaks. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide] (MTT) and neutral red uptake (NRU) cytotoxicity assays indicated 64.48
      +/- 1.6% and 50.73 +/- 2.1% reduction in cell viability with 100 MUg/ml of
      ZnFe2O4-NPs exposure. The treated WISH cells exhibited 1.2-fold higher ROS level
      with 0.9-fold decline in membrane potential (DeltaPsim) and 7.4-fold higher DNA
      damage after 48h of ZnFe2O4-NPs treatment. Real-time PCR (qPCR) analysis of p53,
      CASP 3 (caspase-3), and bax genes revealed 5.3, 1.6, and 14.9-fold upregulation,
      and 0.18-fold down regulation of bcl 2 gene vis-a-vis untreated control. RT(2)
      ProfilerTM PCR array data elucidated differential up-regulation of mRNA
      transcripts of IL-1b, NFKB1, NOS2 and CCL21 genes in the range of 1.5 to 3.7
      folds. The flow cytometry based cell cycle analysis suggested the transfer of
      15.2 +/- 2.1% (p<0.01) population of ZnFe2O4-NPs (100 MUg/ml) treated cells into
      apoptotic phase through intrinsic pathway. Over all, the data revealed the
      potential of ZnFe2O4-NPs to induce cellular and genetic toxicity in cells of
      placental origin. Thus, the significant ROS production, reduction in DeltaPsim,
      DNA damage, and activation of genes linked to inflammation, oxidative stress,
      proliferation, DNA damage and repair could serve as the predictive toxicity and
      stress markers for ecotoxicological assessment of ZnFe2O4-NPs induced cellular
      and genetic damage.

PMID- 24035973
TI  - Endocrine disruptors found in food contaminants enhance allergic sensitization
      through an oxidative stress that promotes the development of allergic airway
      inflammation.
AB  - In the past few decades, there has been a significant increase in incidence of
      allergic diseases. The hygiene hypothesis may provide some clues to explain this
      rising trend, but it may also be attributable to other environmental factors that
      exert a proallergic adjuvant effects. However, there is limited information on
      the risks of developing allergic asthma and related diseases through the
      ingestion of environmental chemicals found in food contaminants. In the present
      study, we have shown that oral administration of tributyltin, used as a model
      environmental chemical, induced oxidative-stress status in the bronchial lymph
      node, mesenteric lymph node and spleen, but not in the lung, where the initial
      step of allergic asthma pathogenesis takes place. Mice exposed to tributyltin
      exhibited heightened Th2 immunity to the allergen with more severe airway
      inflammation. Tributyltin also induced Treg cells apoptosis preferentially over
      non-Treg cells. All these effects of tributyltin exposure were canceled by the
      administration of glutathione monoethyl ester. Meanwhile, tributyltin did not
      affect airway inflammation of mice transferred with allergen-specific Th2 cells.
      Collectively, these results suggest that tributyltin exerts its pathological
      effect during the sensitization phase through oxidative stress that enhances the
      development of allergic diseases. The current study dissects the pathogenic role
      of oxidative stress induced by oral exposure to an environmental chemical during
      the sensitization phase of allergic airway inflammation and would be important
      for developing therapeutics for prevention of allergic diseases. 

PMID- 24035975
TI  - Targeting tumors with nanobodies for cancer imaging and therapy.
AB  - The use of monoclonal antibodies has revolutionized both cancer therapy and
      cancer imaging. Antibodies have been used to directly inhibit tumor cell
      proliferation or to target drugs to tumors. Also in molecular imaging, monoclonal
      antibodies have found their way to the clinic. Nevertheless, distribution within
      tumors is hampered by their size, leading to insufficient efficacy of cancer
      treatment and irregular imaging. An attractive alternative for monoclonal
      antibodies are nanobodies or VHHs. These are the variable domain of heavy-chain
      antibodies from animals from the Camelidae family that were first discovered in
      1993. Stimulated by the ease of nanobody selection, production, and low
      immunogenicity potential, a number of nanobodies specific to different disease
      related targets have been developed. For cancer therapy, nanobodies have been
      employed as antagonistic drugs, and more recently, as targeting moieties of
      effector-domaINS and of drug delivery systems. In parallel, nanobodies have also
      been employed for molecular imaging with modalities such as nuclear and optical
      imaging. In this review, we discuss recent developments in the application of
      nanobodies as targeting moieties in cancer therapy and cancer imaging. With such
      a wide range of successful applications, nanobodies have become much more than
      simple antagonists. 

PMID- 24035974
TI  - Systemic tumor-specific gene delivery.
AB  - The objective of a systemically administered cancer gene therapy is to achieve
      gene expression that is isolated to the tumor tissue. Unfortunately, viral
      systems have strong affinity for the liver, and delivery from non-viral cationic
      systems often results in high expression in the lungs. Non-specific delivery to
      these organs must be overcome if tumors are to be aggressively treated with genes
      such as IL-12 which activates a tumor immune response, and TNF-alpha which can
      induce tumor cell apoptosis. Techniques which have led to specific expression in
      tumor tissue include receptor targeting through ligand conjugation, utilization
      of tumor specific promoters and viral mutation in order to take advantage of
      proteins overexpressed in tumor cells. This review analyzes these techniques
      applied to liposomal, PEI, dendrimer, stem cell and viral gene delivery systems
      in order to determine the techniques that are most effective in achieving tumor
      specific gene expression after systemic administration. 

PMID- 24035976
TI  - Mucoadhesive intestinal devices for oral delivery of salmon calcitonin.
AB  - One of the major challenges faced by therapeutic polypeptides remains their
      invasive route of delivery. Oral administration offers a potential alternative to
      injections; however, this route cannot be currently used for peptides due to
      their limited stability in the stomach and poor permeation across the intestine.
      Here, we report mucoadhesive devices for oral delivery that are inspired by the
      design of transdermal patches and demonstrate their capabilities in vivo for
      salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a
      polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose
      (1:1:2), and were coated on all sides but one with an impermeable and flexible
      ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution,
      mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco
      2 monolayer transport) and in vivo in rats. Devices showed steady drug release
      with ~75% cumulative drug released in 5h. Devices also demonstrated strong
      mucoadhesion to porcine small intestine to withstand forces up to 100 times their
      own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco
      2 monolayers and across the intestinal epithelium in vivo in rats. A ~52-fold
      (pharmacokinetic) and ~44-fold (pharmacological) enhancement of oral
      bioavailability was observed with mucoadhesive devices when compared to direct
      intestinal injections. Oral delivery of devices in enteric coated capsules
      resulted in significant bioavailability enhancement. 

PMID- 24035977
TI  - Evaluation of drug delivery profiles in geometric three-layered tablets with
      various mechanical properties, in vitro-in vivo drug release, and Raman imaging.
AB  - Even though various multi-layered tablets have been developed for sustained
      release formulations, evaluations of mechanical properties during dissolution
      with drug release and imaging in the tablets have been limited. A novel geometric
      system consisting of an inner immediate release layer and two extended release
      barrier layers with swellable hydrophilic polymers was suggested as a once-a-day
      formulation. To evaluate drug release mechanisms with geometric properties,
      various mechanical characteristics during swelling were investigated to
      comprehend the relationship among in vitro drug release, human pharmacokinetics,
      and geometric characteristics. Imaging of drug movement was also studied in real
      time using Raman spectroscopy. Drug delivery in the tablets might be divided into
      three processes through the geometric properties. When exposed to aqueous
      environments, the drug in the mid-layer was released until wrapped by the swollen
      barrier layers. Then, the drug in the mid-layer was mainly delivered to the
      barrier layers and a small amount of the drug was delivered to the contact region
      of the swollen barrier layers. Finally, the delivered drug to the barrier layers
      was consistently released out in response to the characteristics of the polymer
      of the barrier layers. Using Raman spectroscopy, these processes were confirmed
      in real-time analysis. Moreover, in vitro drug release profiles and human
      pharmacokinetics showed consistent results suggesting that drug release might be
      dependent on the various geometric properties and be modified consistently during
      the formulation development. 

PMID- 24035978
TI  - Enhanced drug-loading and therapeutic efficacy of hydrotropic oligomer-conjugated
      glycol chitosan nanoparticles for tumor-targeted paclitaxel delivery.
AB  - Enhanced drug-loading and therapeutic efficacies are highly essential properties
      for nanoparticles as tumor-targeting drug carriers. Herein, we developed the
      glycol chitosan nanoparticles with hydrotropic oligomers (HO-CNPs) as a new tumor
      targeting drug delivery system. For enhancing drug-loading efficiency of
      paclitaxel in drug carriers, hydrotropic 2-(4-(vinylbenzyloxy)-N,N
      diethylnicotinamide) (VBODENA-COOH) oligomers, that were used for enhancing the
      aqueous solubility of paclitaxel, were directly conjugated to glycol chitosan
      polymers. The amphiphilic conjugates readily formed nanoparticle structure
      (average size=302 +/- 22 nm) in aqueous condition. Water-insoluble paclitaxel
      (PTX) was readily encapsulated into HO-CNPs with a high drug-loading amount up to
      24.2 wt.% (2.4 fold higher than other polymeric nanoparticles) by a simple
      dialysis method. The PTX encapsulated HO-CNPs (PTX-HO-CNPs; average size=343 +/-
      12 nm) were very stable in aqueous media up to 50 days. Also, PTX-HO-CNPs
      presented rapid cellular uptake and lower cytotoxicity in cell culture system,
      compared to Cremophor EL/ethanol formulation of PTX. In tumor-bearing mice, the
      extravasation and accumulation of PTX-HO-CNPs in tumor tissue were precisely
      observed by intravital fluorescence imaging techniques. Furthermore, PTX-HO-CNPs
      showed the higher therapeutic efficacy, compared to Abraxane(r), a commercialized
      PTX-formulation. These overall results demonstrate its potential as a new nano
      sized PTX carrier for cancer treatment.

PMID- 24035980
TI  - Stability studies for titanium dioxide nanoparticles upon adsorption of Suwannee
      River humic and fulvic acids and natural organic matter.
AB  - In many studies humic acid, fulvic acid, or natural organic matter is used
      interchangeably to model the effect of naturally derived organic matter on
      geochemical processes in the environment. In this study, the term NOOM (naturally
      occurring organic matter) is used to include both humic and fulvic acids as well
      as natural organic matter and compares the effect of NOOM type on NOOM removal
      onto nano-TiO2. In general, regardless of variations in solution chemistry, the
      order of the percentage of removal of NOOM onto nano-TiO2 was humic acid>natural
      organic matter>fulvic acid. The order of adsorption constant values of NOOM onto
      nano-TiO2 was also found to be humic acid>natural organic matter>fulvic acid
      under all conditions studied. The extent of NOOM removal by nano-TiO2 was
      enhanced in the presence of the divalent ions, magnesium and calcium, at pH7.8
      when compared to the presence of the monovalent ions, sodium and potassium. Also,
      lower NOOM removal by nano-TiO2 in the presence of sodium salts of dihydrogen
      phosphate, bicarbonate and nitrate relative to chloride was observed and was
      likely due to the competition between polyatomic anions and NOOM adsorption onto
      the surface of nano-TiO2 indicating an anionic effect. Low concentrations of NOOM
      (10-20 mg L(-1)) destabilized nano-TiO2 in solution, however, the stability of
      nano-TiO2 increased as the amount of NOOM adsorbed onto nano-TiO2 increased at
      higher dissolved NOOM concentrations and significant stabilization was seen at 25
      mg L(-1) NOOM. Thus, the three fractions of NOOM, humic and fulvic acids and
      natural organic matter and their concentrations were found to affect nano-TiO2
      stability to different degrees although pH dependent trends in cation and anion
      effects had similar patterns. While the effects of adsorption of these three
      commonly used types of NOOM onto nanoparticles are similar, there are important
      differences that can be related to structural differences.

PMID- 24035979
TI  - Persistence of non-viral vector mediated RPE65 expression: case for viability as
      a gene transfer therapy for RPE-based diseases.
AB  - Mutations in the retinal pigment epithelium (RPE) gene RPE65 are associated with
      multiple blinding diseases including Leber's Congenital Amaurosis (LCA). Our goal
      has been to develop persistent, effective non-viral genetic therapies to treat
      this condition. Using precisely engineered DNA vectors and high capacity
      compacted DNA nanoparticles (NP), we previously demonstrated that both plasmid
      and NP forms of VMD2-hRPE65-S/MAR improved the disease phenotypes in an rpe65(-/
      ) model of LCA up to 6 months post-injection (PI), however the duration of this
      treatment efficacy was not established. Here, we test the ability of these
      vectors to sustain gene expression and phenotypic improvement for the life of the
      animal. NPs or naked DNA were subretinally injected in rpe65(-/-) mice at
      postnatal day (P) 16 and evaluated at 15 months PI. Quantitative real-time PCR
      (qRT-PCR) and immunofluorescence were performed at PI-15 months and demonstrated
      appreciable expression of transferred RPE65 (levels were 32% of wild-type [WT]
      for NPs and 44% of WT for naked DNA). No reduction in expression at the message
      level was observed from PI-6 month data. Spectral electroretinography (ERG)
      demonstrated significant improvement in cone ERG amplitudes in treated versus
      uninjected animals. Most importantly, we also observed reduced fundus
      autofluorescence in the eyes injected with NP and naked DNA compared to
      uninjected counterparts. Consistent with these observations, biochemical studies
      showed a reduction in the accumulation of toxic retinyl esters in treated mice,
      suggesting that the transferred hRPE65 was functional. These critical results
      indicate that both NP and uncompacted plasmid VMD2-hRPE65-S/MAR can mediate
      persistent, long-term improvement in an RPE-associated disease phenotype, and
      suggest that DNA NPs, which are non-toxic and have a large payload capacity,
      expand the treatment repertoire available for ocular gene therapy.

PMID- 24035981
TI  - Rainwater trifluoroacetic acid (TFA) in Guangzhou, South China: levels, wet
      deposition fluxes and source implication.
AB  - The origin of trifluoroacetic acid (TFA) occurring in hydrosphere has long been a
      controversial issue. Hydrochlorofluorocarbons and hydrofluorocarbons (HCFCs/HFCs)
      as replacements of chlorofluorocarbons (CFCs) are precursors of TFA in the
      atmosphere, their contribution to rainwater TFA is a concern as their ambient
      mixing ratios are continually growing. Here we present rainwater TFA monitored
      from April 2007 to March 2008 in urban Guangzhou, a central city in south China's
      highly industrialized and densely populated Pearl River Delta region. Rainwater
      TFA levels ranged 45.8-974 ng L(-1) with a median of 166 ng L(-1). TFA levels
      negatively correlated with rainfall amount, the yearly rainfall-weighted average
      for TFA was 152 ng L(-1). The annual TFA wet deposition flux was estimated to be
      229 g km(-2) yr(-1), and the total wet deposition of TFA reached ~1.7 tyr(-1) in
      Guangzhou. The Two-Box model was applied to estimate attributions of HCFCs/HFCs
      and fluoropolymers to rainwater TFA assuming TFA generated was proportional to
      gross domestic product (GDP), gross industrial product (GIP) or number of private
      cars. The results revealed that the degradation of HCFCs/HFCs and fluoropolymers
      could explain 131.5-152.4 ng L(-1) rainwater TFA, quite near the observed
      rainfall-weighted annual mean of 152 ng L(-1), suggesting rainwater TFA in
      Guangzhou was predominantly originated from these anthropogenic precursors.
      HCFCs/HFCs accounted for 83.3-96.5% of rainwater TFA observed, while
      fluoropolymers' contributions were minor (~5%). HFC-134a alone could explain 55.9
      90.0% of rainwater TFA, and its contribution would be greatly enhanced with its
      wide use in mobile air conditioning systems and rapid increase in ambient mixing
      ratios.

PMID- 24035982
TI  - Clay mineral type effect on bacterial enteropathogen survival in soil.
AB  - Enteropathogens released into the environment can represent a serious risk to
      public health. Soil clay content has long been known to have an important effect
      on enteropathogen survival in soil, generally enhancing survival. However, clay
      mineral composition in soils varies, and different clay minerals have specific
      physiochemical properties that would be expected to impact differentially on
      survival. This work investigated the effect of clay materials, with a
      predominance of a particular mineral type (montmorillonite, kaolinite, or
      illite), on the survival in soil microcosms over 96 days of Listeria
      monocytogenes, Salmonella Dublin, and Escherichia coli O157. Clay mineral
      addition was found to alter a number of physicochemical parameters in soil,
      including cation exchange capacity and surface area, and this was specific to the
      mineral type. Clay mineral addition enhanced enteropathogen survival in soil. The
      type of clay mineral was found to differentially affect enteropathogen survival
      and the effect was enteropathogen-specific.

PMID- 24035983
TI  - Reply: To PMID 23103371.

PMID- 24035984
TI  - Reply: To PMID 23123381.

PMID- 24035985
TI  - Customized large-for-gestational-age birthweight at term and the association with
      adverse perinatal outcomes.
AB  - OBJECTIVE: Using a cohort of 110,447 singleton, term pregnancies, we aimed to
      validate the previously proposed customized standard of large-for-gestational-age
      (LGA) birthweight, derive an additional customized LGA model excluding maternal
      weight, and evaluate the association between differing definitions of customized
      LGA and perinatal morbidities. STUDY DESIGN: Three customized LGA
      classifications, in addition to a population-based 90th percentile, were made
      according to the principals described by Gardosi: (1) customized LGA using
      Gardosi's previously published coefficients (LGA-Gardosi), (2) customized LGA
      using coefficients derived by a similar method but from our larger cohort, and
      (3) derived without customization for maternal weight. Associations between the
      LGA classifications and various perinatal morbidity outcomes were evaluated.
      RESULTS: Coefficients derived here for physiologic and pathologic effects on
      birthweight were similar to those previously reported by Gardosi. Customized LGA
      (any method) generally identified more births to younger, nonwhite, nulliparous
      mothers with female neonates of lower birthweight compared with population-based
      LGA. Rates of maternal and neonatal morbidity were greatest in births classified
      by both population-based LGA and customized LGA (any method). However, the model
      that excluded customization for maternal weight, revealed a greater proportion of
      women previously unidentified by population-based LGA who were more frequently
      black (40% vs 25%) and obese (30% vs 5.1%), along with greater rates of shoulder
      dystocia, neonatal intensive care unit admission and neonatal respiratory
      complications, than with LGA-Gardosi. CONCLUSION: The use of customized methods
      of defining LGA was not decisively superior compared with population-based LGA,
      but custom LGA may be improved by modification of the parameters included in
      customization.

PMID- 24035986
TI  - Changing diagnostic criteria for gestational diabetes: are implications the same
      for every country?

PMID- 24035987
TI  - From narcotics to antibiotics: evolving concepts in the treatment of lower back
      pain.

PMID- 24035988
TI  - Translation experiments in traumatic brain injury ... is it time to renew
      pharmacologic therapy?

PMID- 24035989
TI  - Flow diversion and the almighty dollar.

PMID- 24035990
TI  - Evaluating the role of CCM1 loss-of-function-induced endothelial-to-mesenchymal
      transition in cavernous malformation development.

PMID- 24035991
TI  - Importance of the venous outflow pattern in predicting hyperemic complications
      after treatment of cerebral arteriovenous malformations.

PMID- 24035992
TI  - Spinal deformity? There's an app for that!

PMID- 24035993
TI  - Deferred imitation in 18-month-olds from two cultural contexts: the case of
      Cameroonian Nso farmer and German-middle class infants.
AB  - Imitative learning has been described in naturalistic studies for different
      cultures, but lab-based research studying imitative learning across different
      cultural contexts is almost missing. Therefore, imitative learning was assessed
      with 18-month-old German middle-class and Cameroonian Nso farmer infants -
      representing two highly different eco-cultural contexts associated with different
      cultural models, the psychological autonomy and the hierarchical relatedness - by
      using the deferred imitation paradigm. Study 1 revealed that the infants from
      both cultural contexts performed a higher number of target actions in the
      deferred imitation than in the baseline phase. Moreover, it was found that German
      middle-class infants showed a higher mean imitation rate as they performed more
      target actions in the deferred imitation phase compared with Cameroonian Nso
      farmer infants. It was speculated that the opportunity to manipulate the test
      objects directly after the demonstration of the target actions could enhance the
      mean deferred imitation rate of the Cameroonian Nso farmer infants which was
      confirmed in Study 2. Possible explanations for the differences in the amount of
      imitated target actions of German middle-class and Cameroonian Nso farmer infants
      are discussed considering the object-related, dyadic setting of the imitation
      paradigm with respect to the different learning contexts underlying the different
      cultural models of learning. 

PMID- 24035994
TI  - Mumps among highly vaccinated people: investigation of an outbreak in a French
      Military Parachuting Unit, 2013.

PMID- 24035996
TI  - PAQR3 has modulatory roles in obesity, energy metabolism, and leptin signaling.
AB  - Diet-induced obesity is commonly associated with leptin resistance, and
      attenuated leptin signaling contributes to the progression of obesity. PAQR3 is a
      member of the progesterone and AdipoQ receptor (PAQR) family with close homology
      to adiponectin receptors. We hypothesized that PAQR3 is implicated in the
      regulation of obesity and energy homeostasis. To address this hypothesis, we fed
      Paqr3-deleted mice with high-fat diet (HFD), followed by analyses to evaluate
      obesity, hepatic steatosis, insulin resistance, metabolic rate, and leptin
      signaling. We found that mice with deletion of Paqr3 are resistant to HFD-induced
      obesity and hepatic steatosis, accompanied by improvement of insulin resistance
      and insulin signaling. Paqr3-deleted mice have an increased energy expenditure
      and physical activity. HFD-induced leptin resistance is reversed by Paqr3
      ablation. Overexpression of PAQR3 reduces leptin signaling whereas deletion of
      Paqr3 enhances leptin signaling in the hypothalamus. In conclusion, this study
      reveals that PAQR3 has an important physiological function in modulating obesity,
      energy metabolism, and leptin signaling. 

PMID- 24035995
TI  - Cooperative effects of 17beta-estradiol and oocyte-derived paracrine factors on
      the transcriptome of mouse cumulus cells.
AB  - Oocyte-derived paracrine factors (ODPFs) and estrogens are both essential for the
      development and function of ovarian follicles in mammals. Cooperation of these
      two factors was assessed in vitro using intact cumulus-oocyte complexes, cumulus
      cells cultured after the removal of oocytes [oocytectomized (OOX) cumulus cells],
      and OOX cumulus cells cocultured with denuded oocytes, all in the presence or
      absence of 17beta-estradiol (E2). Effects on the cumulus cell transcriptome were
      assessed by microarray analysis. There was no significant difference between the
      cumulus cell transcriptomes of either OOX cumulus cells cocultured with oocytes
      or intact cumulus-oocyte complexes. Therefore, oocyte-mediated regulation of the
      cumulus cell transcriptome is mediated primarily by ODPFs and not by gap
      junctional communication between oocytes and cumulus cells. Gene ontology
      analysis revealed that both ODPFs and E2 strongly affected the biological
      processes associated with cell proliferation in cumulus cells. E2 had limited
      effects on ODPF-regulated biological processes. However, in sharp contrast, ODPFs
      significantly affected biological processes regulated by E2 in cumulus cells. For
      example, only in the presence of ODPFs did E2 significantly promote the
      biological processes related to phosphorylation-mediated signal transduction in
      cumulus cells, such as the signaling pathways of epidermal growth factor,
      vascular endothelial growth factor, and platelet-derived growth factor.
      Therefore, ODPFs and E2 cooperate to regulate the cumulus cell transcriptome and,
      in general, oocytes modulate the effects of estrogens on cumulus cell function. 

PMID- 24035997
TI  - FFAR1 is involved in both the acute and chronic effects of palmitate on insulin
      secretion.
AB  - Free fatty acids (FFAs) have pleiotropic effects on the pancreatic beta-cell.
      Although acute exposure to FFAs stimulates glucose-stimulated insulin secretion
      (GSIS), prolonged exposure impairs GSIS and causes apoptosis. FFAs exert their
      effects both via intracellular metabolism and interaction with the FFA receptor 1
      (FFAR1/GPR40). Here we studied the role of FFAR1 in acute and long-term effects
      of palmitate on GSIS and insulin content in isolated human islets by using the
      FFAR1 agonist TAK-875 and the antagonist ANT203. Acute palmitate exposure
      potentiated GSIS approximately 3-fold, whereas addition of the antagonist
      decreased this potentiation to approximately 2-fold. In the absence of palmitate,
      the agonist caused a 40% increase in GSIS. Treatment with palmitate for 7 days
      decreased GSIS to 70% and insulin content to 25% of control level. These negative
      effects of long-term exposure to palmitate were ameliorated by FFAR1 inhibition
      and further aggravated by additional stimulation of the receptor. In the absence
      of extracellularly applied palmitate, long-term treatment with the agonist caused
      a modest increase in GSIS. The protective effect of FFAR1 inhibition was verified
      by using FFAR1-deficient MIN6 cells. Improved beta-cell function by the
      antagonist was paralleled by the decreased apoptosis and lowered oxidation of
      palmitate, which may represent the potential mechanisms of protection. We
      conclude that FFAR1 in the pancreatic beta-cell plays a substantial role not only
      in acute potentiation of GSIS by palmitate but also in the negative long-term
      effects of palmitate on GSIS and insulin content. 

PMID- 24035999
TI  - Depression of type I diacylglycerol kinases in pancreatic beta-cells from male
      mice results in impaired insulin secretion.
AB  - Diacylglycerol kinase (DGK) catalyzes the conversion of diacylglycerol (DAG) to
      phosphatidic acid. This study investigated the expression and function of DGK in
      pancreatic beta-cells. mRNA expression of type I DGK isoforms (alpha, beta,
      gamma) was detected in mouse pancreatic islets and the beta-cell line MIN6.
      Protein expression of DGKalpha and DGKgamma was also detected in mouse beta-cells
      and MIN6 cells. The type I DGK inhibitor R59949 inhibited high K(+)- and glucose
      induced insulin secretion in MIN6 cells. Moreover, single knockdown of DGKalpha
      or DGKgamma by small interfering RNA slightly but significantly decreased glucose
      and high K(+)-induced insulin secretions, and the double knockdown further
      decreased them to the levels comparable with those induced by R59949. R59949 and
      DiC8, a membrane permeable DAG analog, decreased intracellular Ca(2+)
      concentration elevated by glucose and high K(+) in MIN6 cells. Real-time imaging
      in MIN6 cells expressing green fluorescent protein-tagged DGKalpha or DGKgamma
      showed that the DGK activator phorbol 12-myristate 13-acetate rapidly induced
      translocation of DGKgamma to the plasma membrane, whereas high K(+) slowly
      translocated DGKalpha and DGKgamma to the plasma membrane. R59949 increased the
      DAG content in MIN6 cells when stimulated with high KCl, whereas it did not
      increase the DAG content but decreased the phosphatidic acid content when
      stimulated with high glucose. Finally, R59949 was confirmed to inhibit high K(+)
      induced insulin secretion from mouse islets and glucose-induced insulin secretion
      from rat islets. These results suggest that DGKalpha and DGKgamma are present in
      beta-cells and that the depression of these DGKs causes a decrease in
      intracellular Ca(2+) concentration, thereby reducing insulin secretion. 

PMID- 24035998
TI  - Inhibitors of SCF-Skp2/Cks1 E3 ligase block estrogen-induced growth stimulation
      and degradation of nuclear p27kip1: therapeutic potential for endometrial cancer.
AB  - In many human cancers, the tumor suppressor, p27(kip1) (p27), a cyclin-dependent
      kinase inhibitor critical to cell cycle arrest, undergoes perpetual ubiquitin
      mediated proteasomal degradation by the E3 ligase complex SCF-Skp2/Cks1 and/or
      cytoplasmic mislocalization. Lack of nuclear p27 causes aberrant cell cycle
      progression, and cytoplasmic p27 mediates cell migration/metastasis. We
      previously showed that mitogenic 17-beta-estradiol (E2) induces degradation of
      p27 by the E3 ligase Skp1-Cullin1-F-Box- S phase kinase-associated
      protein2/cyclin dependent kinase regulatory subunit 1 in primary endometrial
      epithelial cells and endometrial carcinoma (ECA) cell lines, suggesting a
      pathogenic mechanism for type I ECA, an E2-induced cancer. The current studies
      show that treatment of endometrial carcinoma cells-1 (ECC-1) with small molecule
      inhibitors of Skp2/Cks1 E3 ligase activity (Skp2E3LIs) stabilizes p27 in the
      nucleus, decreases p27 in the cytoplasm, and prevents E2-induced proliferation
      and degradation of p27 in endometrial carcinoma cells-1 and primary ECA cells.
      Furthermore, Skp2E3LIs increase p27 half-life by 6 hours, inhibit cell
      proliferation (IC50, 14.3MUM), block retinoblastoma protein (pRB)
      phosphorylation, induce G1 phase block, and are not cytotoxic. Similarly, using
      super resolution fluorescence localization microscopy and quantification,
      Skp2E3LIs increase p27 protein in the nucleus by 1.8-fold. In vivo, injection of
      Skp2E3LIs significantly increases nuclear p27 and reduces proliferation of
      endometrial epithelial cells by 42%-62% in ovariectomized E2-primed mice.
      Skp2E3LIs are specific inhibitors of proteolytic degradation that
      pharmacologically target the binding interaction between the E3 ligase, SCF
      Skp2/Cks1, and p27 to stabilize nuclear p27 and prevent cell cycle progression.
      These targeted inhibitors have the potential to be an important therapeutic
      advance over general proteasome inhibitors for cancers characterized by SCF
      Skp2/Cks1-mediated destruction of nuclear p27. 

PMID- 24036001
TI  - Risk assessment of 'endocrine substances': guidance on identifying endocrine
      disruptors.
AB  - The European regulation on plant protection products (1107/2009) and other
      related legislation only support the marketing and use of chemical products on
      the basis that they do not induce endocrine disruption in humans or wildlife
      species. This legislation would appear to make the assumption that endocrine
      active chemicals should be managed differently from other chemicals presumably
      due to an assumed lack of a threshold for adverse effects. In the absence of
      agreed scientific criteria and guidance on how to identify and evaluate endocrine
      activity and disruption within these pieces of legislation, a European Centre for
      Ecotoxicology and Toxicology of Chemicals (ECETOC) task force was formed to
      provide scientific criteria that may be used within the context of these three
      legislative documents. The first ECETOC technical report and associated workshop,
      held in 2009, presented a science-based concept on how to identify endocrine
      activity and disrupting properties of chemicals for both human health and the
      environment. Specific scientific criteria for the determination of endocrine
      activity and disrupting properties that integrate information from both
      regulatory toxicity studies and mechanistic/screening studies were proposed.
      These criteria combined the nature of the adverse effects detected in studies
      which give concern for endocrine toxicity with an understanding of the mode of
      action of toxicity so that adverse effects can be explained scientifically. A key
      element in the data evaluation is the consideration of all available information
      in a weight-of-evidence approach. Both sets of data (evidence of the adverse
      effect in apical studies and conclusive mode of action knowledge) are essential
      in order to correctly identify endocrine disruption according to accepted
      definitions. As the legislation seeks to regulate chemicals on a mode of action
      rather than the more traditional approach of adverse endpoints, then conclusive
      evidence of the mode of action of concern should be presented. From a human
      safety perspective and in the absence of any compelling data that endocrine
      active chemicals exert their adverse effects through anything other than a
      threshold mechanism there is no scientific justification for not using a margin
      of exposure approach to risk assessment in order to best protect human health. 

PMID- 24036000
TI  - DHEA-mediated inhibition of the pentose phosphate pathway alters oocyte lipid
      metabolism in mice.
AB  - Women with polycystic ovary syndrome (PCOS) and hyperandrogenism have altered
      hormone levels and suffer from ovarian dysfunction leading to subfertility. We
      have attempted to generate a model of hyperandrogenism by feeding mice chow
      supplemented with dehydroepiandrosterone (DHEA), an androgen precursor that is
      often elevated in women with PCOS. Treated mice had polycystic ovaries, low
      ovulation rates, disrupted estrous cycles, and altered hormone levels. Because
      DHEA is an inhibitor of glucose-6-phosphate dehydrogenase, the rate-limiting
      enzyme in the pentose phosphate pathway, we tested the hypothesis that oocytes
      from DHEA-exposed mice would have metabolic disruptions. Citrate levels, glucose
      6-phosphate dehydrogenase activity, and lipid content in denuded oocytes from
      these mice were significantly lower than controls, suggesting abnormal
      tricarboxylic acid and pentose phosphate pathway metabolism. The lipid and
      citrate effects were reversible by supplementation with nicotinic acid, a
      precursor for reduced nicotinamide adenine dinucleotide phosphate. These findings
      suggest that elevations in systemic DHEA can have a negative impact on oocyte
      metabolism and may contribute to poor pregnancy outcomes in women with
      hyperandrogenism and PCOS. 

PMID- 24036002
TI  - Pre-emptive virology screening in the pediatric hematopoietic stem cell
      transplant population: a cost effectiveness analysis.
AB  - BACKGROUND AND OBJECTIVES: Pediatric patients undergoing hematopoietic stem cell
      transplant (HSCT) are at a uniquely high risk of cytomegalovirus (CMV) and
      Epstein-Barr virus (EBV) infections. The pre-emptive treatment model whereby
      asymptomatic post-transplant patients are routinely screened with treatment
      initiated if found viremic has recently been shown to be superior in terms of
      patient mortality when compared to deferring laboratory assessment and treatment
      until symptoms emerge. This study analyzes the cost-effectiveness of the pre
      emptive therapy model in patient care dollars per quality-adjusted life years
      (QALY). PATIENTS AND METHODS: Utilization and outcome data were compiled as a
      retrospective cohort study of 96 pediatric patients receiving HSCT at University
      of California Los Angeles Pediatric Hematology/Oncology Department between the
      years 2006 and 2010. Two-decision tree models were constructed for each the pre
      emptive model and the deferred model wherein costs and probability assumptions
      were based on either previously published literature or calculated from this
      study cohort. RESULTS: The pre-emptive model resulted in a five-year survival of
      71%, during which time 4% of patients were found to be EBV viremic, while 33%
      were found to be CMV viremic. The average actual cost of EBV/CMV virology
      screening per patient in the cohort following the pre-emptive model was $9699
      while the expected cost following the deferred model was $19,284. This results in
      an incremental cost effectiveness ratio illustrating pre-emptive model cost
      savings of $2367/QALY. CONCLUSION: These results support the financial viability
      and prudence of scheduled screening for subclinical viremia for achieving optimal
      outcomes in a cost-effective manner in the pediatric HSCT population.

PMID- 24036003
TI  - Semantic concept-enriched dependence model for medical information retrieval.
AB  - OBJECTIVE: In medical information retrieval research, semantic resources have
      been mostly used by expanding the original query terms or estimating the concept
      importance weight. However, implicit term-dependency information contained in
      semantic concept terms has been overlooked or at least underused in most previous
      studies. In this study, we incorporate a semantic concept-based term-dependence
      feature into a formal retrieval model to improve its ranking performance. DESIGN:
      Standardized medical concept terms used by medical professionals were assumed to
      have implicit dependency within the same concept. We hypothesized that, by
      elaborately revising the ranking algorithms to favor documents that preserve
      those implicit dependencies, the ranking performance could be improved. The
      implicit dependence features are harvested from the original query using MetaMap.
      These semantic concept-based dependence features were incorporated into a
      semantic concept-enriched dependence model (SCDM). We designed four different
      variants of the model, with each variant having distinct characteristics in the
      feature formulation method. MEASUREMENTS: We performed leave-one-out cross
      validations on both a clinical document corpus (TREC Medical records track) and a
      medical literature corpus (OHSUMED), which are representative test collections in
      medical information retrieval research. RESULTS: Our semantic concept-enriched
      dependence model consistently outperformed other state-of-the-art retrieval
      methods. Analysis shows that the performance gain has occurred independently of
      the concept's explicit importance in the query. CONCLUSION: By capturing implicit
      knowledge with regard to the query term relationships and incorporating them into
      a ranking model, we could build a more robust and effective retrieval model,
      independent of the concept importance.

PMID- 24036004
TI  - Unsupervised mining of frequent tags for clinical eligibility text indexing.
AB  - Clinical text, such as clinical trial eligibility criteria, is largely underused
      in state-of-the-art medical search engines due to difficulties of accurate
      parsing. This paper proposes a novel methodology to derive a semantic index for
      clinical eligibility documents based on a controlled vocabulary of frequent tags,
      which are automatically mined from the text. We applied this method to
      eligibility criteria on ClinicalTrials.gov and report that frequent tags (1)
      define an effective and efficient index of clinical trials and (2) are unlikely
      to grow radically when the repository increases. We proposed to apply the
      semantic index to filter clinical trial search results and we concluded that
      frequent tags reduce the result space more efficiently than an uncontrolled set
      of UMLS concepts. Overall, unsupervised mining of frequent tags from clinical
      text leads to an effective semantic index for the clinical eligibility documents
      and promotes their computational reuse. 

PMID- 24036005
TI  - A versatile liquid chromatographic technique for pharmacokinetic estimation of
      curcumin in human plasma.
AB  - A simple, rapid, sensitive and specific liquid chromatographic method was
      developed and validated for the determination of curcumin in human plasma.
      Berberine was used as the internal standard. Chromatographic separation was
      achieved on a Zorbax Eclipse C18 column at 40  degrees C, with a mobile phase
      consisting of 1% acetic acid (pH 3 adjusted with 50% triethanolamine):
      acetonitrile (55:45), at a flow rate of 1.25 mL/min. The method was validated for
      precision, accuracy, linearity, lower limit of quantification (LLOQ) and
      extraction efficiency according to the International Conference on Harmonization
      guidelines. The method was successfully developed with an LLOQ of 10 ng/mL and a
      runtime of 9 min. Linearity range was from 10 to 1000 ng/mL. Curcumin and
      Berberine were well separated with retention times of 8.2 +/- 0.2 and 1.4 +/- 0.1
      min, respectively. Further, the method was successfully employed to study the
      pharmacokinetic parameters of curcumin, following oral administration of curcumin
      loaded hydroxy propyl cellulose (HPC) nanoparticles and curcumin suspension in
      female Wistar rats. Curcumin-loaded HPC nanoparticles (Cmax: 106.01 +/- 20.11
      ng/mL) showed significant improvement in pharmacokinetic parameters when compared
      with curcumin suspension (Cmax: 30.13 +/- 0.47 ng/mL) indicating 43.73-fold
      increase in relative bioavailability.

PMID- 24036006
TI  - Invincibility fable: tool development to measure invincibility.
AB  - Invincibility is a phase of social-cognitive development of the adolescent and
      has been associated with risk behavior involvement. OBJECTIVE: To determine
      psychometric properties of the Adolescent Invincibility Tool (AIT). METHODS:
      Reliability was assessed and validity was examined using principal components
      analysis. RESULTS: Internal consistency was demonstrated with a Cronbach's alpha
      of .88; factor analysis led to the confirmation of subscales. Criterion validity
      was validated with similar and opposing measures of invincibility. DISCUSSION:
      Initial testing suggests that the AIT is a valid and reliable tool for screening
      invincibility. Further testing is recommended to determine relevance for other
      populations of youth.

PMID- 24036008
TI  - Prognosis of patients with advanced hepatocellular carcinoma who failed first
      line systemic therapy.
AB  - BACKGROUND & AIMS: No approved therapy is available for patients with advanced
      hepatocellular carcinoma (HCC) who fail first-line therapy. The prognosis of
      these patients, especially those eligible for clinical trials of second-line
      therapy, is unclear. METHODS: All patients who participated in clinical trials of
      first-line systemic therapy for metastatic or locally advanced HCC in a referral
      center of Taiwan between 2005 and 2011 were included. Their clinicopathologic
      characteristics, when the first-line treatment failed, were analyzed and
      correlated with the overall survival (OS) from the date of first-line treatment
      failure. RESULTS: A total of 192 patients were included. Before the start of the
      first-line therapy, all patients had Child-Pugh class A liver reserves and Cancer
      of the Liver Italian Program (CLIP) scores <=4. After the failure of the first
      line therapy, the median OS of the entire group was 4.0 months. Patients with
      Child-Pugh class A liver reserves, when the first-line treatment failed, had
      significantly better OS than patients with Child-Pugh class B or C liver reserves
      (median, A vs. B vs. C=7.5 vs. 1.3 vs. 1.0 month, p<0.001). According to the key
      eligibility criteria of 3 published clinical trials for second-line therapy, 41%
      56% of patients were potentially eligible. Compared to patients who were
      ineligible for clinical trials, potentially eligible patients had longer OS with
      a median of 7.8-8.6 months. CONCLUSIONS: Patients with advanced HCC who failed
      first-line therapy could have substantially improved prognosis if they had Child
      Pugh A liver reserves or were potentially eligible for clinical trials.

PMID- 24036007
TI  - Multiparametric magnetic resonance for the non-invasive diagnosis of liver
      disease.
AB  - BACKGROUND & AIMS: With the increasing prevalence of liver disease worldwide,
      there is an urgent clinical need for reliable methods to diagnose and stage liver
      pathology. Liver biopsy, the current gold standard, is invasive and limited by
      sampling and observer dependent variability. In this study, we aimed to assess
      the diagnostic accuracy of a novel magnetic resonance protocol for liver tissue
      characterisation. METHODS: We conducted a prospective study comparing our
      magnetic resonance technique against liver biopsy. The individual components of
      the scanning protocol were T1 mapping, proton spectroscopy and T2* mapping, which
      quantified liver fibrosis, steatosis and haemosiderosis, respectively. Unselected
      adult patients referred for liver biopsy as part of their routine care were
      recruited. Scans performed prior to liver biopsy were analysed by physicians
      blinded to the histology results. The associations between magnetic resonance and
      histology variables were assessed. Receiver-operating characteristic analyses
      were also carried out. RESULTS: Paired magnetic resonance and biopsy data were
      obtained in 79 patients. Magnetic resonance measures correlated strongly with
      histology (r(s)=0.68 p<0.0001 for fibrosis; r(s)=0.89 p<0.001 for steatosis;
      r(s)=-0.69 p<0.0001 for haemosiderosis). The area under the receiver operating
      characteristic curve was 0.94, 0.93, and 0.94 for the diagnosis of any degree of
      fibrosis, steatosis and haemosiderosis respectively. CONCLUSION: The novel
      scanning method described here provides high diagnostic accuracy for the
      assessment of liver fibrosis, steatosis and haemosiderosis and could potentially
      replace liver biopsy for many indications. This is the first demonstration of a
      non-invasive test to differentiate early stages of fibrosis from normal liver.

PMID- 24036009
TI  - Expression of HLA-G by mast cells is associated with hepatitis C virus-induced
      liver fibrosis.
AB  - BACKGROUND & AIMS: Infection with hepatitis C virus is a worldwide health
      problem. An inadequate Th2 cytokine response promotes the fibrosis-cirrhosis
      fate. Immune-modulating molecules favoring a Th2 profile, such as HLA-G molecules
      of the HLA class Ib family, may play a role in chronic hepatitis. HLA-G
      contributes to the escape of tumors, and their involvement in viral infections
      has been increasingly described. The aim of this work was to study the expression
      of HLA-G in the liver, its cellular source and its regulation in cases of chronic
      C hepatitis. METHODS: HLA-G cells in blocks of liver derived from patients
      infected with HCV were labeled by immunohistochemistry and enumerated. Double
      immunofluorescence allowed the identification of the cellular source. HLA-G
      secretion by a human mast cell line was quantified by ELISA after various
      stimulations. After treatment with IFN-alpha, real-time PCR was performed to
      determine the kinetics of cytokine expression profiles, followed by heat map
      clustering analysis. RESULTS: The number of HLA-G+ cells was significantly
      associated with the area of fibrosis. For the first time, we identify the HLA-G+
      cells as being mast cells. HLA-G secretion was significantly induced in human
      mast cells stimulated by IL-10 or interferons of class I. The transcriptome of
      the secretome of this cell line stimulated by IFN-alpha revealed that (i) the HLA
      G gene is upregulated late, and that (ii) T lymphocytes and NK cells are
      recruited. CONCLUSIONS: These findings suggest an autocrine loop in the genesis
      of HCV liver fibrosis, based on mast cells expressing HLA-G.

PMID- 24036010
TI  - Polymer encapsulation of inorganic nanoparticles for biomedical applications.
AB  - Hybrid inorganic colloidal particles have attracted a great attention in the last
      years, and they have been largely used in various applications and more
      particularly in biomedical nanotechnology. Recently, they are used as carriers
      for biomolecules, and exploited for use in microsystems, microfluidics and in lab
      on-a chip based bionanotechnology. Various kinds of hybrid particles can be
      listed starting from classical inorganic nanoparticles such as silica, gold,
      silver, iron oxide and those exhibiting intrinsic properties such as
      semiconducting nanoparticles (e.g. quantum dots). As a general tendency, to be
      conveniently used in biomedical applications, the encapsulation of the inorganic
      nanoparticles in a polymer matrix is incontestably needed. Consequently, various
      chemistry-based encapsulation processes have been developed and showed promising
      results as compared to the encapsulation using preformed polymers. 

PMID- 24036011
TI  - Development of long-acting bioadhesive vaginal gels of oxybutynin: formulation,
      in vitro and in vivo evaluations.
AB  - Overactive bladder (OAB) and vaginal dryness are common problems after menopause.
      Oxybutynin (OXY) is an antimuscarinic agent that has been available for more than
      30 years in the treatment of OAB patients. The aim of the work reported in this
      paper was to develop long acting mucoadhesive gel formulations of OXY and to
      investigate their effects on blood levels compared to those of oral OXY immediate
      release tablets, in rabbits. Mucoadhesive gels were prepared with chitosan,
      hydroxypropyl methylcellulose (HPMC K100M) and Poloxamer 407 (Pluronic F 127).
      The physicopharmaceutical properties of gels were evaluated. The gel formulation
      which was prepared with HPMC K100M, exhibited the highest viscosity, the greatest
      adhesiveness, cohesiveness and mucoadhesion values. The formulation which was
      prepared from HPMC K100M showed suitable permeation characteristics across the
      vaginal mucosa. Comparative bioavailability studies were carried out on rabbits
      with vaginal HPMC gel, vaginal chitosan gel, vaginal OXY solution and
      commercially available oral Uropan tablets. It was concluded that the highest AUC
      and relative bioavailability values were obtained for the bioadhesive vaginal gel
      formulation prepared with HPMC K100M. Therefore, the mucoadhesive vaginal gels of
      OXY can be a promising and innovative alternative therapeutic system for the
      treatment of OAB. It can be safely used in cases of overactive bladder and as
      well as vaginal dryness after menopause.

PMID- 24036012
TI  - Nanocarriers for intravenous injection--the long hard road to the market.
AB  - Nanodispersed drug delivery systems for the intravenous injection have
      successfully overcome the hurdle of drug approval in the European Union and the
      United States. Although there is a need for highly advanced nanocarrier devices
      they have not been the result of a rational formulation design but were developed
      as stand-alone products in a long chain of case-by-case studies. This review
      focuses on aspects in development, composition, and manufacture of these
      innovative dosage forms that are relevant for the translation into new drug
      products. 

PMID- 24036013
TI  - Estrogenic control of behavioral sex change in the bluehead wrasse, Thalassoma
      bifasciatum.
AB  - Estrogens activate male-typical sexual behavior in several mammalian and avian
      models. Estrogen signaling also appears critical in the control of sex change in
      some fishes, in which it is instead decreases in estradiol levels that may permit
      development of male-typical behaviors. The bluehead wrasse is a protogynous
      hermaphrodite that exhibits rapid increases in aggressive and male-typical
      courtship behavior as females undergo sex change. Removal of the ovaries does not
      prevent these changes. In two field experiments involving gonadally-intact and
      gonadectomized females, estradiol (E2) implants prevented behavioral sex change
      in large females who were made the largest members of their social groups through
      removals of more dominant fish. In contrast, cholesterol-implanted control
      females showed full behavioral sex change, along with a higher frequency both of
      aggressive interactions and of male-typical courtship displays than occurred in
      E2-implanted animals. To assess potential neural correlates of these behavioral
      effects of E2, we evaluated abundances of aromatase mRNA using in situ
      hybridization. Aromatase mRNA was more abundant in the POA of E2-implanted
      females than in cholesterol-implanted controls in gonadally-intact females. The
      lack of behavioral sex change coupled with increased levels of aromatase mRNA are
      consistent with an inhibitory role for E2, likely of neural origin, in regulating
      socially controlled sex change. 

PMID- 24036014
TI  - Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence
      and mortality: a systematic review and meta-analysis.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis of longitudinal
      studies on the association of 25(OH)D with total cancer incidence and mortality.
      METHOD: Relevant longitudinal observational studies were identified by
      systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge
      databases. Due to the heterogeneity across studies in categorizing 25(OH)D
      concentration, all results were recalculated for an increase of 25(OH)D by 50
      nmol/L. RESULTS: In meta-analyses with random effects models, the summary risk
      ratios and confidence intervals (RRs (95% CI)) for the association of an increase
      of 25(OH)D by 50 nmol/L with total cancer incidence (5 studies) and mortality (13
      studies) were 0.89 (0.81, 0.97) and 0.83 (0.71, 0.96), respectively. In sex
      specific analyses no significant association with total cancer incidence was
      observed among men or women. A clear inverse association with total cancer
      mortality was observed among women (0.76 (0.60, 0.98)) but not among men (0.92
      (0.65, 1.32)). Large heterogeneity was observed for studies on total cancer
      mortality (P<0.01) but not for studies on cancer incidence (P=0.41). No
      publication bias was found. CONCLUSION: The meta-analysis suggests a moderate
      inverse association of 25(OH)D concentration with total cancer incidence and
      mortality.

PMID- 24036016
TI  - [Editorial comment: Pediatrics as a multidisciplinary discipline].

PMID- 24036015
TI  - Middle school food environments and racial/ethnic differences in sugar-sweetened
      beverage consumption: findings from the Healthy Choices study.
AB  - BACKGROUND: Prior studies have demonstrated disproportionate clustering of fast
      food outlets around schools. PURPOSE: The purpose of this study is to determine
      if racial/ethnic differences in middle school student self-reported sugar
      sweetened beverage (SSB) consumption is explained by differential distributions
      of food outlets surrounding their schools. METHODS: Baseline (2005) data were
      analyzed from 18,281 middle school students in 47 Massachusetts schools
      participating in Healthy Choices, an obesity prevention program. Linear mixed
      effects models were used to examine the association of individual race/ethnicity
      and daily SSB consumption and the potential mediating effect of the density of
      food outlets (the number of fast food outlets and convenience stores in a 1500 m
      buffer area surrounding the school) on this association adjusting for individual
      and school demographics. RESULTS: More SSB consumption was reported by students
      of all racial/ethnic minority groups compared to their White peers except Asians.
      The density of fast food restaurants and convenience stores was not associated
      with individual SSB consumption (beta=0.001, p=0.875) nor did it mediate the
      association of race/ethnicity and SSB consumption. CONCLUSIONS: Racial and ethnic
      differences in SSB consumption among MA middle school students cannot be fully
      explained by the location of fast food restaurants and convenience stores.

PMID- 24036017
TI  - [Some clinical aspects of sodium homeostasis disorders].
AB  - In this review three major issues of sodium homeostasis are addressed.
      Specifically, volume-dependent (salt-sensitive) hypertension, sodium chloride
      content of maintenance fluid and clinical evaluation of hyponatremia are
      discussed. Regarding volume-dependent hypertension the endocrine/paracrine
      systems mediating renal sodium retention, the relationship between salt intake,
      plasma sodium levels and blood pressure, as well as data on the dissociation of
      sodium and volume regulation are presented. The concept of perinatal programming
      of salt-preference is also mentioned. Some theoretical and practical aspects of
      fluid therapy are summarized with particular reference to using hypotonic sodium
      chloride solution for maintenance fluid as opposed to the currently proposed
      isotonic sodium chloride solution. Furthermore, the incidence, the aetiological
      classification and central nervous system complications of hyponatremia are
      presented, too. In addition, clinical and pathophysical features of hyponatremic
      encephalophathy and osmotic demyelinisation are given. The adaptive reactions of
      the brain to hypotonic stress are also described with particular emphasis on the
      role of brain-specific water channel proteins (aquaporin-4) and the benzamil
      inhibitable sodium channels. In view of the outmost clinical significance of
      hyponatremia, the principles of efficient and safe therapeutic approaches are
      outlined.

PMID- 24036018
TI  - [Chronic morbidities of premature newborns].
AB  - The most important chronic morbidities of premature newborns, deeply influencing
      quality of life, are retinopathy of prematurity, bronchopulmonary dysplasia,
      intraventricular hemorrhage and periventricular leukomalacia. Since the rate of
      premature birth has not decreased in recent years in Hungary, and treatments of
      these end stage disorders are extremely difficult, prevention gains tremendous
      significance. Effective prevention is based on detailed knowledge of the
      pathophysiological mechanisms of these special diseases having multifactorial
      nature sharing several common risk factors, and one is the pathological
      angiogenesis. This sensitive system is affected by several stress situations
      which are the consequences of prematurity leading to abnormal vascular growth.
      After birth, relative hyperoxia, compared to intrauterine life, and decreasing
      concentrations of vascular growth factors result in vascular injury, moreover,
      may cause vessel apoptosis. The consequence of this phenomenon is the activation
      of hypoxia responsible genes resulting in robust pathological neovascularization
      and organ damage during the later phase. Saving normal angiogenesis and
      inhibiting reactive neovascularization may lead to better quality of life in
      these premature infants.

PMID- 24036019
TI  - [Milestones in understanding the pathogenesis of immunmediated intestinal
      disorders. Evolution of their diagnosis and therapy].
AB  - In the last decades our knowledge has been enormously broadened about the
      structure and function of the gut associated lymphoid system. It was recognized
      how intricate and finely tuned connection exists between the gut bacterial flora
      and the intestinal mucosa. This subtle balance ensures mucosal homeostasis, which
      has a key role in organ defence against pathogens. However, at the same time this
      system makes possible the development of oral tolerance toward the commensals and
      the food antigens. In case of any disturbances in this finely tuned process,
      immunmediated intestinal disorders may easily develop. The first part of this
      paper reviews the structure and function of the mucosal immune system, while the
      second part surveys the pathogenesis, diagnosis and therapy of coeliac disease,
      inflammatory bowel disease and cow's milk allergy induced enteropathy.

PMID- 24036021
TI  - The myeloperoxidase -463G/A polymorphism and coronary artery disease risk: A meta
      analysis of 1938 cases and 1990 controls.
AB  - OBJECTIVES: Genetic polymorphism of human myeloperoxidase (MPO) -463G/A has been
      implicated to alter the risk of coronary artery disease (CAD), but the results
      are controversial. To improve the reliability of the conflicting results, we
      conducted a meta-analysis of studies relating the MPO -463G/A polymorphism with
      the risk of CAD. DESIGN AND METHODS: Two investigators independently searched the
      MEDLINE, EMBASE and Cochrane Library up to June, 2012. Summary odds ratios (OR)
      and 95% confidence interval (CI) for the MPO -463G/A polymorphism and CAD risk
      were calculated, and potential sources of heterogeneity and publication bias were
      explored. Statistical analysis was performed with the software program of Stata
      9.0. RESULTS: 5 case-control studies were finally identified for analyses,
      involving 1938 cases with CAD and 1990 controls. We found that the MPO -463G/A
      polymorphism has no significant association with overall CAD risk (G/G vs A/A:
      OR=0.595, 95%CI=0.298-1.188, P=0.141; G/G vs G/A+A/A: OR=0.886, 95%CI=0.779
      1.008, P=0.066; G/G+G/A vs A/A: OR=0.611, 95%CI=0.334-1.119, P=0.111; OR=0.886,
      95%CI=0.779-1.008, P=0.066; G vs A: OR=0.843, 95%CI=0.675-1.053, P=0.133). The
      heterogeneity test showed that there were significant differences between
      individual studies in additive, recessive and allelic genetic models (P=0.008,
      P=0.021, P=0.019, respectively); further analyses revealed that age and sex
      possibly account for the heterogeneity. CONCLUSIONS: Our meta-analysis
      demonstrated the evidence that there was no significant association between the
      MPO -463G/A polymorphism and the risk of CAD; larger and well-designed
      multicenter studies are needed to confirm our results.

PMID- 24036022
TI  - Novel application of digital microfluidics for the detection of biotinidase
      deficiency in newborns.
AB  - OBJECTIVE: Newborn screening for biotinidase deficiency can be performed using a
      fluorometric enzyme assay on dried blood spot specimens. As a pre-requisite to
      the consolidation of different enzymatic assays onto a single platform, we
      describe here a novel analytical method for detecting biotinidase deficiency
      using the same digital microfluidic cartridge that has already been demonstrated
      to screen for five lysosomal storage diseases (Pompe, Fabry, Gaucher, Hurler and
      Hunter) in a multiplex format. METHODS: A novel assay to quantify biotinidase
      concentration in dried blood spots (DBS) was developed and optimized on the
      digital microfluidic platform using proficiency testing samples from the Centers
      for Disease Control and Prevention. The enzymatic assay uses 4-methylumbelliferyl
      biotin as the fluorogenic substrate. Biotinidase deficiency assays were performed
      on normal (n=200) and deficient (n=7) newborn DBS specimens. RESULTS: Enzymatic
      activity analysis of biotinidase deficiency revealed distinct separation between
      normal and affected DBS specimens using digital microfluidics and these results
      matched the expected activity. CONCLUSIONS: This study has demonstrated
      performance of biotinidase deficiency assays by measurement of 4
      methylumbelliferyl product on a digital microfluidic platform. Due to the
      inherent ease in multiplexing on such a platform, consolidation of other
      fluorometric assays onto a single cartridge may be realized.

PMID- 24036023
TI  - Effect of percutaneous closure of patent foramen ovale on post-procedural
      arrhythmias.

PMID- 24036025
TI  - Stent thrombosis with drug-eluting stents: is the paradigm shifting?
AB  - First-generation drug-eluting stents (DES), which impart the controlled release
      of sirolimus or paclitaxel from durable polymers to the vessel wall, have been
      consistently shown to reduce the risk of restenosis and target vessel
      revascularization compared with bare metal stents (BMS). However, stent
      thrombosis (ST) emerged as a major safety concern with first-generation DES early
      after their adoption in clinical practice, requiring prolonged dual antiplatelet
      therapy. Pathological studies have shown that first-generation DES are associated
      with delayed arterial healing and polymer hypersensitivity reactions resulting in
      chronic inflammation, predisposing to late and very late ST. Second-generation
      DES have been developed to overcome these issues with improved stent designs and
      construction and the use of biocompatible and bioabsorbable polymers. Meta
      analyses have shown that the thin-strut, fluoropolymer-coated cobalt-chromium
      everolimus-eluting stent (CoCr-EES) may be associated with lower rates of
      definite ST than other DES and, unexpectedly, even lower than BMS. The thin-strut
      structure of the stent platform, the thromboresistant properties of the
      fluoropolymer, and the reduced polymer and drug load may contribute to the low
      rate of ST with CoCr-EES. The notion of DES being safer than BMS represents a
      paradigm shift in the evolution of percutaneous coronary intervention. The
      relative safety and efficacy of fluoropolymer-coated CoCr-EES, DES with
      bioabsorbable polymers, and fully bioresorbable scaffolds are the subject of
      numerous ongoing large-scale trials. 

PMID- 24036024
TI  - Intracoronary cardiosphere-derived cells after myocardial infarction: evidence of
      therapeutic regeneration in the final 1-year results of the CADUCEUS trial
      (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction).
AB  - OBJECTIVES: This study sought to report full 1-year results, detailed magnetic
      resonance imaging analysis, and determinants of efficacy in the prospective,
      randomized, controlled CADUCEUS (CArdiosphere-Derived aUtologous stem CElls to
      reverse ventricUlar dySfunction) trial. BACKGROUND: Cardiosphere-derived cells
      (CDCs) exerted regenerative effects at 6 months in the CADUCEUS trial. Complete
      results at the final 1-year endpoint are unknown. METHODS: Autologous CDCs (12.5
      to 25 * 10(6)) grown from endomyocardial biopsy specimens were infused via the
      intracoronary route in 17 patients with left ventricular dysfunction 1.5 to 3
      months after myocardial infarction (MI) (plus 1 infused off-protocol 14 months
      post-MI). Eight patients were followed as routine-care control patients. RESULTS:
      In 13.4 months of follow-up, safety endpoints were equivalent between groups. At
      1 year, magnetic resonance imaging revealed that CDC-treated patients had smaller
      scar size compared with control patients. Scar mass decreased and viable mass
      increased in CDC-treated patients but not in control patients. The single patient
      infused 14 months post-MI responded similarly. CDC therapy led to improved
      regional function of infarcted segments compared with control patients. Scar
      shrinkage correlated with an increase in viability and with improvement in
      regional function. Scar reduction correlated with baseline scar size but not with
      a history of temporally remote MI or time from MI to infusion. The changes in
      left ventricular ejection fraction in CDC-treated subjects were consistent with
      the natural relationship between scar size and ejection fraction post-MI.
      CONCLUSIONS: Intracoronary administration of autologous CDCs did not raise
      significant safety concerns. Preliminary indications of bioactivity include
      decreased scar size, increased viable myocardium, and improved regional function
      of infarcted myocardium at 1 year post-treatment. These results, which are
      consistent with therapeutic regeneration, merit further investigation in future
      trials. (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar
      dySfunction [CADUCEUS]; NCT00893360).

PMID- 24036026
TI  - Colchicine and the heart: pushing the envelope.
AB  - Colchicine, a natural and ancient drug still used today, is traditionally
      considered the staple therapy for gout and a second-line treatment for
      pericarditis, as well as a basic part of familial Mediterranean fever and
      Behcet's disease management. It is commonly classified as an anti-inflammatory
      agent, although its mechanism of action does not involve the arachidonic acid
      pathway affected by non-steroid anti-inflammatory drugs and glucocorticoids.
      Colchicine inhibits microtubule polymerization by binding to tubulin, thus
      affecting any process that requires cytoskeletal changes, including cell mitosis
      and neutrophil motility. Recent studies suggest that colchicine may prove to be
      useful in a much wider spectrum of cardiovascular diseases than previously
      suspected, rekindling the interest in this old drug. In this review we briefly
      present the biochemical characteristics, mechanism of action and side-effects of
      colchicine, as well as examine what is currently known about the promising role
      of colchicine in cardiovascular medicine beyond pericardial disease.

PMID- 24036028
TI  - Undetected large aortopulmonary window in an adult: a confluence of great
      vessels.

PMID- 24036027
TI  - Cardiovascular care facts: a report from the national cardiovascular data
      registry: 2011.
AB  - OBJECTIVES: The aim of this report was to characterize the patients,
      participating centers, and measures of quality of care and outcomes for 5 NCDR
      (National Cardiovascular Data Registry) programs: 1) ACTION (Acute Coronary
      Treatment and Intervention Outcomes Network) Registry-GWTG (Get With The
      Guidelines) for acute coronary syndromes; 2) CathPCI Registry for coronary
      angiography and percutaneous coronary intervention; 3) CARE (Carotid Artery
      Revascularization and Endarterectomy) Registry for carotid revascularization; 4)
      ICD Registry for implantable cardioverter defibrillators; and the 5) PINNACLE
      (Practice INNovation And CLinical Excellence) Registry for outpatients with
      cardiovascular disease (CVD). BACKGROUND: CVD is a leading cause of death and
      disability in the United States. The quality of care for patients with CVD is
      suboptimal. National registry programs, such as NCDR, permit assessments of the
      quality of care and outcomes for broad populations of patients with CVD. METHODS:
      For the year 2011, we assessed for each of the 5 NCDR programs: 1) demographic
      and clinical characteristics of enrolled patients; 2) key characteristics of
      participating centers; 3) measures of processes of care; and 4) patient outcomes.
      For selected variables, we assessed trends over time. RESULTS: In 2011 ACTION
      Registry-GWTG enrolled 119,967 patients in 567 hospitals; CathPCI enrolled
      632,557 patients in 1,337 hospitals; CARE enrolled 4,934 patients in 130
      hospitals; ICD enrolled 139,991 patients in 1,435 hospitals; and PINNACLE
      enrolled 249,198 patients (1,436,328 individual encounters) in 74 practices
      (1,222 individual providers). Data on performance metrics and outcomes, in some
      cases risk-adjusted with validated NCDR models, are presented. CONCLUSIONS: The
      NCDR provides a unique opportunity to understand the characteristics of large
      populations of patients with CVD, the centers that provide their care, quality of
      care provided, and important patient outcomes.

PMID- 24036029
TI  - Prevalence and outcomes of unoperated patients with severe symptomatic mitral
      regurgitation and heart failure: comprehensive analysis to determine the
      potential role of MitraClip for this unmet need.

PMID- 24036030
TI  - Refeeding syndrome in a patient with anorexia nervosa.

PMID- 24036031
TI  - Slope calculation for the LVAD ramp test.

PMID- 24036032
TI  - Quantification of typical antipsychotics in human plasma by ultra-high
      performance liquid chromatography tandem mass spectrometry for therapeutic drug
      monitoring.
AB  - A selective and sensitive method was developed for the simultaneous
      quantification of seven typical antipsychotic drugs (cis-chlorprothixene,
      flupentixol, haloperidol, levomepromazine, pipamperone, promazine and
      zuclopenthixol) in human plasma. Ultra-high performance liquid chromatography
      (UHPLC) was used for complete separation of the compounds in less than 4.5min on
      an Acquity UPLC BEH C18 column (2.1mm*50mm; 1.7MUm), with a gradient elution of
      ammonium formate buffer pH 4.0 and acetonitrile at a flow rate of 400MUl/min.
      Detection was performed on a tandem quadrupole mass spectrometer (MS/MS) equipped
      with an electrospray ionization interface. A simple protein precipitation
      procedure with acetonitrile was used for sample preparation. Thanks to the use of
      stable isotope-labeled internal standards for all analytes, internal standard
      normalized matrix effects were in the range of 92-108%. The method was fully
      validated to cover large concentration ranges of 0.2-90ng/ml for haloperidol, 0.5
      90ng/ml for flupentixol, 1-450ng/ml for levomepromazine, promazine and
      zuclopenthixol and 2-900ng/ml for cis-chlorprothixene and pipamperone. Trueness
      (89.1-114.8%), repeatability (1.8-9.9%), intermediate precision (1.9-16.3%) and
      accuracy profiles (<30%) were in accordance with the latest international
      recommendations. The method was successfully used in our laboratory for routine
      quantification of more than 500 patient plasma samples for therapeutic drug
      monitoring. To the best of our knowledge, this is the first UHPLC-MS/MS method
      for the quantification of the studied drugs with a sample preparation based on
      protein precipitation. 

PMID- 24036033
TI  - Pharmacokinetics study of calf thymus DNA in rats and beagle dogs with (3)H
      labeling and tracing method.
AB  - This study developed a radioisotope detection and tracing method to investigate
      the pharmacokinetic properties of calf thymus DNA (ctDNA) in rats and beagle
      dogs. The radioactivity labeling result was detected through gel electrophoresis
      analysis, and pharmacokinetic analytical methods for (3)H-ctDNA in rat and beagle
      dog plasma were developed, respectively. Full method validation indicated that
      the established radioisotope method was sensitive, specific, rapid and reliable,
      and the results were all in accordance with the analysis requirement in
      biological samples. After intravenous administration of the planned doses of (3)H
      ctDNA to the rats and beagle dogs, plasma concentrations from the various dose
      groups declined rapidly. In addition, the radioactive concentration of (3)H-ctDNA
      in the plasma from single and multiple dosings decreased in a similar trend.
      Through comparative analysis of the pharmacokinetic parameters, we inferred that
      the elimination of ctDNA accorded with the linear pharmacokinetic characteristic.
      The results demonstrated that ctDNA was rapidly eliminated in rat and beagle dog
      plasma and would not accumulate, indicating the safe use of ctDNA as an
      immunoadsorptive material without bringing out potential risk. 

PMID- 24036034
TI  - Development and validation of an UPLC-PDA method to quantify daptomycin in human
      plasma and in dried plasma spots.
AB  - Quantification of daptomycin in plasma samples may be useful in optimizing
      therapy especially in special patients' population. Nevertheless, therapeutic
      drug monitoring of daptomycin is still limited probably for the low number of
      laboratories which perform this analysis and for high shipment costs. We
      developed and validated a new UPLC-PDA method to quantify daptomycin in plasma
      and in dried plasma spots (DPS) collected on dried sample spots devices (DSSD).
      Daptomycin and quinoxaline, used as internal standard, were monitored at 262nm
      and 253nm, respectively. Daptomycin was extracted from plasma using acetonitrile
      and from DPS using an extraction solution (ethyl acetate-acetic acid-acetone
      water; 50:20:20:10, v/v/v/v). Both assays were linear over the calibration range
      of 0.781 to 200MUg/ml. Considering the method of extraction from plasma, mean
      intra and inter-day accuracy was -1.18% and -2.79%, respectively. Mean intra and
      inter-day precision was 7.91% and 9.22%, respectively. Regarding the extraction
      method from DPS, mean intra and inter-day accuracy was 2.21% and 2.41%,
      respectively. Mean intra and inter-day precision was 8.01% and 9.19%,
      respectively. Daptomycin in DPS was found to be stable for 7 days at room
      temperature (20-25 degrees C) and for at least 30 days at 4 degrees C. A
      statistically significant (p<0.001) linear correlation was found between
      daptomycin extracted from plasma and from DPS (r(2)=0.919). DPS represents a safe
      and cheap strategy to store and ship plasma samples. Thus, it is suited for
      pharmacokinetic studies and therapeutic drug monitoring of daptomycin in
      hospitals without a therapeutic drug monitoring laboratory. 

PMID- 24036035
TI  - Proteomic analysis of Mycobacterium tuberculosis isolates resistant to kanamycin
      and amikacin.
AB  - Kanamycin (KM) and amikacin (AK) are the key aminoglycoside drugs against
      tuberculosis (TB) and resistance to them severely affects the options for
      treatment. Many explanations have been proposed for drug resistance to these
      drugs but still some mechanisms are unknown. Proteins are the functional moiety
      of the cell and manifest in most of the biological processes; so, these are
      potential foci for the development of new therapeutics, diagnostics and vaccine.
      We examined the KM and AK resistant isolates of Mycobacterium tuberculosis using
      proteomic analysis comprising of two dimensional gel electrophoresis (2DGE),
      matrix assisted laser desorption ionization time-of-flight/time-of flight (MALDI
      TOF/TOF) and bioinformatic tools like BLASTP, InterProScan, KEGG motif scan and
      molecular docking. Proteins intensities of twelve spots were found to be
      consistently increased in KM and AK resistant isolates and these were identified
      as Rv3867, Rv1932, Rv3418c, Rv1876, Rv2031c, Rv0155, Rv0643c, Rv3224, Rv0952, and
      Rv0440. Among these, Rv3867 and Rv3224 were identified as proteins with unknown
      function. All the proteins identified were cellular proteins. Molecular docking
      shows the proper interaction of both drugs with these molecules. Also, Rv1876 and
      Rv3224 were found to be probably involved in iron regulation/metabolism
      indicating the role of iron in imparting resistance to second line drugs.
      BIOLOGICAL SIGNIFICANCE: The study that was carried out shows that two
      dimensional electrophoresis along with mass spectrometry is still the best
      approach for proteomic analysis. To the best of our knowledge it is the first
      ever report on proteomic analysis of M. tuberculosis isolates resistant to second
      line drugs (kanamycin and amikacin). The major finding implicates that the
      genes/proteins involved in iron metabolism and the two hypothetical proteins
      (Rv3867 and Rv3224) might be playing some crucial role in contributing resistance
      to second line drugs. Further exploitation in this direction may lead to the
      development of newer therapeutics against tuberculosis.

PMID- 24036036
TI  - Simultaneous detection of kinase and phosphatase activities of polynucleotide
      kinase using molecular beacon probes.
AB  - Phosphorylation and dephosphorylation of DNA by polynucleotide kinase (PNK) has
      an important role in DNA damage repair, replication, and recombination.
      Traditionally, it is assayed by denaturing gel electrophoresis and
      autoradiography, which are tedious and not sensitive. We report on the
      development of a sensitive and simple method for PNK assay based on DNA ligation
      using a molecular beacon. Enzyme activity of PNK is measured down to a limit of
      0.002 unit/ml. The method not only provides a universal platform for simultaneous
      monitoring of kinase and phosphatase activities, but also shows great potential
      in biological research, drug discovery, and clinical diagnostics.

PMID- 24036038
TI  - Validation of a specific prolylcarboxypeptidase activity assay and its
      suitability for plasma and serum measurements.
AB  - Prolylcarboxypeptidase (PRCP, EC 3.4.16.2), a lysosomal carboxypeptidase, was
      discovered 45 years ago. However, research has been hampered by a lack of well
      validated assays that are needed to measure low activities in biological samples.
      Two reversed-phase high-performance liquid chromatography (RP-HPLC) methods for
      quantifying PRCP activity in crude homogenates and plasma samples were optimized
      and validated. PRCP activity was determined by measuring the hydrolysis of N
      benzyloxycarbonyl-l-proline (Z-Pro)-Phe. The enzymatically formed Z-Pro and Phe
      were measured independently under different HPLC conditions. The in-house methods
      showed good precision, linearity, accuracy, and specificity. Based on Michaelis
      Menten constants, Z-Pro-Phe was chosen over Z-Pro-Ala as the substrate of
      preference. Cross-reactivity studies with dipeptidyl peptidases (DPPs) 2, 4, and
      9 and prolyl oligopeptidase (PREP) confirmed the specificity of the PRCP activity
      assay. The average PRCP activity in plasma and serum of 32 healthy individuals
      was found to be 0.65 +/- 0.02 and 0.72 +/- 0.03 U/L, respectively. Both methods
      can be used to measure PRCP activity specifically in different biological samples
      and are well suited to evaluate PRCP inhibitors. These well-validated methods are
      valuable tools for studying PRCP's role in cardiovascular diseases, stroke,
      inflammation, and metabolic syndrome.

PMID- 24036037
TI  - Concurrent quantification of tryptophan and its major metabolites.
AB  - An imbalance in tryptophan (TRP) metabolites is associated with several
      neurological and inflammatory disorders. Therefore, analytical methods allowing
      for simultaneous quantification of TRP and its major metabolites would be highly
      desirable, and may be valuable as potential biomarkers. We have developed a HPLC
      method for concurrent quantitative determination of tryptophan, serotonin, 5
      hydroxyindoleacetic acid, kynurenine, and kynurenic acid in tissue and fluids.
      The method utilizes the intrinsic spectroscopic properties of TRP and its
      metabolites that enable UV absorbance and fluorescence detection by HPLC, without
      additional labeling. The origin of the peaks related to analytes of interest was
      confirmed by UV-Vis spectral patterns using a PDA detector and mass spectrometry.
      The developed methods were validated in rabbit fetal brain and amniotic fluid at
      gestational day 29. Results are in excellent agreement with those reported in the
      literature for the same regions. This method allows for rapid quantification of
      tryptophan and four of its major metabolites concurrently. A change in the
      relative ratios of these metabolites can provide important insights in predicting
      the presence and progression of neuroinflammation in disorders such as cerebral
      palsy, autism, multiple sclerosis, Alzheimer disease, and schizophrenia. 

PMID- 24036039
TI  - Block decoys: transcription-factor decoys designed for in vitro gene regulation
      studies.
AB  - Transcription-factor decoys are short synthetic oligodeoxynucleotides that
      sequester cognate transcription factors and prevent their binding at target
      promoters. Current methods of decoy formation have primarily been optimized for
      potential therapeutic applications. However, they are not ideally suited to in
      vitro investigations into multi-transcription factor-mediated processes that may
      require multiple regulatory elements to be inhibited in varying combinations. In
      this study we describe a novel method for chimeric decoy formation in which
      blocks containing discrete transcription factor binding sites are combined into
      circular molecules. Unlike currently available methods, block decoys allow rapid
      construction of chimeric decoys targeting multiple regulatory elements. Further,
      they enable fine-tuning of binding-site copy ratios within chimeras, allowing
      sophisticated control of the cellular transcriptional landscape. We show that
      block decoys are exonuclease-resistant and specifically inhibit expression from
      target binding sites. The potential of block decoys to inhibit multiple elements
      simultaneously was demonstrated using a chimeric decoy containing molar optimized
      ratios of three regulatory elements, NF-kappaB-RE, CRE, and E-box. The chimeric
      decoy inhibited expression from all three elements simultaneously at equivalent
      levels. The primary intended use of block decoys is in vitro gene regulation
      studies in which bespoke chimeras can be rapidly constructed and utilized to
      determine a promoter's functional regulation. 

PMID- 24036040
TI  - Suppression of polyI:C-inducible gene expression by EP3 in murine conjunctival
      epithelium.

PMID- 24036041
TI  - Comparison of serum and urinary calcium profile of immobilized and ambulant
      trauma patients.
AB  - BACKGROUND: Hypercalcemia occurs more frequently than is recognized in patients
      who are immobilized, but most of these patients are asymptomatic. This study is
      to determine serum and urinary calcium levels, incidence of hypercalcemia and
      hypercalciuria in immobilized and ambulant trauma patients. METHODS: A
      prospective comparative study was carried out over a period of seven months.
      Total serum calcium level and 24-hour urinary calcium output were measured weekly
      over 4weeks in 55 immobilized trauma patients as study group and 51 ambulant
      trauma patients as control group. RESULTS: Mean total serum calcium of
      immobilized patients increased progressively (on admission: 2.315+/-0.056mmol/l
      and week 4: 2.552+/-0.231mmol/l, p<.001) while that of ambulant patients did not
      change significantly (on admission: 2.306+/-0.041mmol/l, and week 4: 2.300+/
      0.028mmol/l, p=.348). There is a significant difference in overall mean total
      serum calcium between immobilized and ambulant patients (p<.001). In immobilized
      and ambulant patients, mean 24-hour urinary calcium increased progressively from
      baseline (3.044+/-0.480mmol/day and 3.056+/-0.540mmol/day respectively), till the
      end of the study (8.543+/-2.142mmol/day and 6.783+/-1.372mmol/day respectively).
      Overall mean 24-hour urinary calcium is significantly different between
      immobilized and ambulant patients {multivariate Pillai F (5,100)=883.124,
      p<.001}. Incidence of hypercalcemia increased progressively in immobilized
      patients (end of week 1=7.27% and end of week 4=29.09%) while none of the
      ambulant patients had hypercalcemia. Incidence of hypercalciuria also increased
      progressively in immobilized patients (end of week 1=7.27% and end of week
      4=63.64%) while ambulant patients only had hypercalciuria at the end of week 3
      (9.8%) and week 4 (21.57%). CONCLUSION: Mean total serum calcium increased with
      increased duration of immobilization in trauma patients. Both immobilized and
      ambulant trauma patients developed hypercalciuria but it is worse and earlier in
      the immobilized trauma patients.

PMID- 24036042
TI  - Discovery of 4-amino-2-(thio)phenol derivatives as novel protein kinase and
      angiogenesis inhibitors for the treatment of cancer: synthesis and biological
      evaluation. Part II.
AB  - A novel series of 4-amino-2-(thio)phenol derivatives were well synthesized. The
      preliminary biological test revealed that several compounds displayed high
      specific protein kinase and angiogenesis inhibitory activities compared with
      previous work mainly because of the substitution of sulfonamide structure for
      amide fragment. Among which, compound 5i was identified to inhibit protein kinase
      B/AKT (IC50 = 1.26 MUM) and ABL tyrosine kinase (IC50 = 1.50 MUM) effectively.
      Meanwhile, compound 5i demonstrated competitive in vitro antiangiogenic
      activities to Pazopanib in both human umbilical vein endothelial cell (HUVEC)
      tube formation assay and the rat thoracic aorta rings test.

PMID- 24036043
TI  - Novel N-methylsulfonamide and retro-N-methylsulfonamide derivatives as 17beta
      hydroxysteroid dehydrogenase type 2 (17beta-HSD2) inhibitors with good ADME
      related physicochemical parameters.
AB  - Under physiological conditions healthy bones are maintained by a well tightened
      balance between osteoclast (OCs) and osteoblast (OBs) activity. Disruption of
      this balance leads to osteoporosis characterized by decline in bone function and
      skeletal rigidity. Inhibition of 17beta-hydroxysteroid dehydrogenase type 2
      (17beta-HSD2) could help maintaining the appropriate bone mass density by
      increasing the level of estradiol and testosterone in bone. Herein, we described
      the synthesis, the physicochemical properties and the biological evaluation of
      novel N-methylsulfonamide and retro-N-methylsulfonamide derivatives as 17beta
      HSD2 inhibitors showing high potency (compound 10f, IC50 = 23 nM), with a good
      selectivity toward 17beta-HSD1 (the isoenzyme responsible of the reverse
      reaction), and a likely good in vitro ADME profile. It was also shown that the
      acidity of the phenolic hydroxy correlates with the inhibitory potency,
      suggesting pKa as a predictive parameter for the activity of this class of
      inhibitors.

PMID- 24036044
TI  - FT-IR and Raman spectra, ab initio and density functional computations of the
      vibrational spectra, molecular geometries and atomic charges of uracil and 5
      halogenated uracils (5-X-uracils; X=F, Cl, Br, I).
AB  - Raman (200-4000 cm(-1)) and FT-IR (400-4000 cm(-1)) spectra of uracil and 5
      halogenated uracils (5-X-uracils; X=F, Cl, Br, I) have been recorded and analyzed
      in the range 200-4000 cm(-1). The optimized molecular geometries, atomic polar
      tensor (APT) charges and vibrational characteristics have been studied
      theoretically using restricted Hartree-Fock (RHF) and density functional theory
      (DFT) methods. Ab initio and DFT calculations [using Becke's exchange in
      conjunction with Lee-Yang-Parr's correlation functional and Becke's three
      parameter hybrid method (B3LYP)] were carried out to study the optimized
      molecular fundamental vibrational frequencies for uracil and 5-halogenated
      uracils by employing Gaussian-03 program. Gauss View software was used to make
      the vibrational analysis. Raman and IR spectra have been computed theoretically
      for the uracil and 5-halogenated molecules. The fundamental vibrational
      frequencies along with their corresponding intensities in IR and Raman activities
      and depolarization ratios of the Raman lines have also been calculated using the
      RHF and DFT methods employing different basis sets. Quantum chemical calculations
      helped in the reassignments of some fundamental vibrational modes. Most of the
      B3LYP/6-311++G(**) vibrational frequencies are in excellent agreement with
      available experimental assignments. The ring breathing and kekule stretching
      modes are found to lower magnitudes compared to those for uracil which could be
      due to mass effect of halogen atom in place of the hydrogen atom. The C-X (X=F,
      Cl, Br, I) stretching frequency is distinctly separated from the CH/NH ring
      stretching frequencies on the pyrimidine ring. All other bands have also been
      assigned different fundamentals/overtones/combinations.

PMID- 24036045
TI  - Novel fluorescent 1,8-naphthalimide derivatives containing thiophene and pyrazole
      moieties: synthesis by direct C-H arylation and evaluation of photophysical and
      electrochemical properties.
AB  - A series of novel 1,8-naphthalimide derivatives containing thiophene and pyrazole
      moities were synthesized by direct Pd-catalyzed C-H arylation and then
      characterized by (1)H NMR, (13)C NMR, MALDI-HRMS, and elementary analysis. The
      photophysical and electrochemical properties of the derivatives were also
      investigated. All compounds have green emission both in diluted CH2Cl2 solution
      and solid film. The cyclic voltammetry (CV) measurements showed that the target
      compounds had a lowest unoccupied molecular orbital (LUMO) range from -3.49 eV to
      -3.29 eV and a highest occupied molecular orbital (HOMO) range from -6.04 eV to 
      5.81 eV. Quantum chemical calculations were performed to obtain the optimized
      ground-state geometry as well as the spatial distributions of the HOMO, LUMO
      levels of the compounds.

PMID- 24036046
TI  - The influencing factors of nanosecond pulse homogeneous dielectric barrier
      discharge in air.
AB  - In this paper, a bipolar nanosecond high pulse voltage with 20 ns rising time was
      employed to generate homogeneous dielectric barrier discharges using the plate
      plate electrode configuration in air at atmospheric pressure. The effects of
      pulse peak voltage, gas discharge gap, and dielectric plates made by different
      materials or thicknesses on the discharge homogeneity, voltage-current waveform,
      and optical emission spectra were investigated. Results show that aforementioned
      parameters have a strongly impact on the discharge homogeneity and the optical
      emission spectra, but it is hard to identify definitely their influences on the
      discharge voltage-current waveform. Homogeneous discharges were easily observed
      when using low permittivity dielectric plate and the emission intensity of N2
      (C(3)Piu->B(3)Pig, 0-0, 337.1 nm) increases with the rising of pulse peak voltage
      and the permittivity of dielectric material but decreases with the increasing of
      gas discharge gap and the dielectric plate thickness. The rotational and
      vibrational temperatures (Trot and Tvib) were determined at Trot=350+/-5 K and
      Tvib=3045 K via fitting the simulative spectra of N2 (C(3)Piu->B(3)Pig, 0-2) with
      the measured one.

PMID- 24036047
TI  - Calorimetric studies of the interactions of linker histone H1(0) and its carboxyl
      (H1(0)-C) and globular (H1(0)-G) domains with calf-thymus DNA.
AB  - Histone H1 is a chromatin protein found in most eukaryotes. ITC and CD have been
      used to study the binding of H1(0) and its C-terminal, H1(0)-C, and globular,
      H1(0)-G, domains to a highly polymerized DNA. ITC results indicate that H1(0) and
      H1(0)-C bind tightly to DNA (Ka~1*10(7)), with an unfavorable DeltaH
      (DeltaH~+22kcal/mol) and a favorable DeltaS (-TDeltaS~-30kcal/mol). Binding H1(0)
      G to DNA at 25 degrees C is calorimetrically silent. A multiple independent site
      model fits the ITC data, with the anomaly in the data near saturation attributed
      to rearrangement of bound H1, maximizing the number of binding sites. CD
      experiments indicate that H1(0)/DNA and H1(0)-C/DNA complexes form with little
      change in protein structure but with some DNA restructuring. Salt dependent ITC
      experiments indicate that the electrostatic contribution to binding H1(0) or
      H1(0)-C is small ranging from 6% to 17% of the total DeltaG. 

PMID- 24036048
TI  - The effects of buffers and pH on the thermal stability, unfolding and substrate
      binding of RecA.
AB  - The Escherichia coli protein RecA is responsible for catalysis of the strand
      transfer reaction used in DNA repair and recombination. Previous studies in our
      lab have shown that high concentrations of salts stabilize RecA in a reverse
      anionic Hofmeister series. Here we investigate how changes in pH and buffer alter
      the thermal unfolding and cofactor binding. RecA in 20mM HEPES, MES, Tris and
      phosphate buffers was studied in the pH range from 6.5 to 8.5 using circular
      dichroism (CD), infrared (IR) and fluorescence spectroscopies. The results show
      all of the buffers studied stabilize RecA up to 50 degrees C above the Tris
      melting temperature and influence RecA's ability to nucleate on double-stranded
      DNA. Infrared and CD spectra of RecA in the different buffers do not show that
      secondary structural changes are associated with increased stability or decreased
      ability to nucleate on dsDNA. These results suggest the differences in stability
      arise from decreasing positive charge and/or buffer interactions. 

PMID- 24036049
TI  - Dabigatran-induced esophagitis.

PMID- 24036051
TI  - Dysphagia lusoria caused by Kommerell's diverticulum of the aberrant left
      subclavian artery.

PMID- 24036050
TI  - The breathprints in patients with liver disease identify novel breath biomarkers
      in alcoholic hepatitis.
AB  - BACKGROUND & AIMS: Selected-ion flow-tube mass spectrometry can precisely
      identify trace gases in the human breath, in the parts-per-billion range. We
      investigated whether concentrations of volatile compounds in breath samples
      correlate with the diagnosis of alcoholic hepatitis (AH) and the severity of
      liver disease in patients with AH. METHODS: We recruited patients with liver
      disease from a single tertiary care center. The study population was divided
      between those with AH with cirrhosis (n = 40) and those with cirrhosis with acute
      decompensation from etiologies other than alcohol (n = 40); individuals without
      liver disease served as control subjects (n = 43). We used selected-ion flow-tube
      mass spectrometry to identify and measure 14 volatile compounds in breath samples
      from fasted subjects. We used various statistical analyses to compare clinical
      characteristics and breath levels of compounds among groups and to test the
      correlation between levels of compounds and severity of liver disease. Logistic
      regression analysis was performed to build a predictive model for AH. RESULTS: We
      identified 6 compounds (2-propanol, acetaldehyde, acetone, ethanol, pentane, and
      trimethylamine [TMA]) whose levels were increased in patients with liver disease
      compared with control subjects. Mean concentrations of TMA and pentane (TAP) were
      particularly high in breath samples from patients with AH, compared with those
      with acute decompensation or control subjects (for both, P < .001). Using
      receiver operating characteristic curve analysis, we developed a model for the
      diagnosis of AH based on breath levels of TAP. TAP scores of 36 or higher
      identified the patients with AH (area under the receiver operating characteristic
      curves = 0.92) with 90% sensitivity and 80% specificity. The levels of exhaled
      TMA had a low level of correlation with the severity of AH based on model for end
      stage liver disease score (r = 0.38; 95% confidence interval, 0.07-0.69; P =
      .018). CONCLUSIONS: Based on levels of volatile compounds in breath samples, we
      can identify patients with AH vs patients with acute decompensation or
      individuals without liver disease. Levels of exhaled TMA moderately correlate
      with the severity of AH. These findings might be used in diagnosis of AH or in
      determining patient prognosis.

PMID- 24036052
TI  - A rare tumor of the common hepatic duct causing biliary obstruction.

PMID- 24036053
TI  - Aggressive intravenous fluid resuscitation for preventing post-endoscopic
      retrograde cholangiopancreatography pancreatitis: finally on the right track.

PMID- 24036054
TI  - Treat to target: a proposed new paradigm for the management of Crohn's disease.
AB  - The traditional management of Crohn's disease, which is based on progressive,
      step-wise treatment intensification with re-evaluation of response according to
      symptoms, does not improve long-term outcomes of Crohn's disease and places
      patients at risk for bowel damage. The introduction of novel therapies and the
      development of new approaches to treatment in rheumatoid arthritis led to better
      outcomes for patients. Prominent among these is a "treat to target" strategy that
      is based on regular assessment of disease activity by using objective clinical
      and biological outcome measures and the subsequent adjustment of treatments. This
      approach is complementary to the concept of early intervention in high-risk
      patients. This review evaluates current literature on this topic and proposes a
      definition for the concept of treating to targets for Crohn's disease. 

PMID- 24036055
TI  - Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of
      patients with cirrhosis.
AB  - BACKGROUND & AIMS: Although a low plasma level of branched-chain amino acids
      (BCAAs) is a marker of cirrhosis, it is not clear whether BCAA supplements affect
      disease progression. We performed a multicenter study to evaluate the effects of
      BCAA supplementation on hepatocarcinogenesis and survival in patients with
      cirrhosis. METHODS: We enrolled 299 patients from 14 medical institutions in
      Japan in a prospective, multicenter study in 2009; 267 patients were followed
      through 2011. Patients were given BCAA supplements (5.5-12.0 g/day) for more than
      2 years (n = 85) or no BCAAs (controls, n = 182). The primary end points were
      onset of hepatocellular carcinoma (HCC) and death. Factors associated with these
      events were analyzed by competing risk analysis. RESULTS: During the study
      period, 41 of 182 controls and 11 of 85 patients given BCAAs developed HCC. On
      the basis of the Cox and the Fine and Gray models of regression analyses, level
      of alpha-fetoprotein, ratio of BCAA:tyrosine, and BCAA supplementation were
      associated with development of HCC (relative risk for BCAAs, 0.45; 95% confidence
      interval, 0.24-0.88; P = .019). Sixteen controls and 2 patients given BCAAs died.
      Factors significantly associated with death were Child-Pugh score, blood level of
      urea nitrogen, platelet count, male sex, and BCAA supplementation (relative risk
      of death for BCAAs, 0.009; 95% confidence interval, 0.0002-0.365; P = .015) in
      both regression models. CONCLUSIONS: On the basis of a prospective study, amino
      acid imbalance is a significant risk factor for the onset of HCC in patients with
      cirrhosis. BCAA supplementation reduces the risk for HCC and prolongs survival of
      patients with cirrhosis.

PMID- 24036056
TI  - Comparing quality, safety, and costs of colonoscopies performed by nurse vs
      physician trainees.
AB  - BACKGROUND & AIMS: We evaluated the quality and safety of colonoscopies performed
      by nurse and physician endoscopy trainees as well as the cost differences.
      METHODS: We performed a study of 7 nurse and 8 physician (gastroenterology
      fellows) endoscopy trainees at 2 medical centers in the Netherlands from
      September 2008 through April 2012. At the beginning of the study, the subjects
      had no experience in endoscopy; they were trained in gastrointestinal endoscopy
      according to the regulations of the Dutch Society of Gastroenterology, performing
      a minimum of 100 colonoscopies. Each trainee then performed 135 consecutive
      colonoscopies (866 total by nurse trainees and 1080 by physician trainees) under
      supervision of a gastroenterologist; the colonoscopies were evaluated for quality
      and safety. We performed statistical analyses of data, assessing multilevel and
      cost minimization. The mean age of the patients was 57 years, and about half were
      women in each group. RESULTS: The endoscopic quality and safety were comparable
      between nurse and physician trainees. Overall rates of cecal intubation were 95%
      for nurses and 93% for physicians (P = .38), including procedures that required
      assistance from a supervisor; mean withdrawal times were 10.4 and 9.8 minutes,
      respectively (P = .44). Each group detected 27% of adenomas and had a 0.5% rate
      of complication. In both groups, the rates of unassisted cecal intubation
      gradually increased with the number of colonoscopies performed, from 70% for
      nurses and 74% for physicians at the beginning to 89% and 86%, respectively, at
      the end of the assessment period. Using a strategy in which 1 gastroenterologist
      supervises 3 nurses, the personnel costs decreased from $64.65 to $54.58.
      CONCLUSIONS: In a supervised setting, nurse endoscopists perform colonoscopies
      according to quality and safety standards that are comparable with those of
      physician endoscopist and can substantially reduce costs.

PMID- 24036057
TI  - Pathogenesis of colonic diverticulosis: repainting the picture.

PMID- 24036058
TI  - Thin-plate spline analysis of mandibular morphological changes induced by early
      class III treatment: a long-term evaluation.
AB  - OBJECTIVE: To evaluate the long-term mandibular morphological changes induced by
      early treatment of class III malocclusion with rapid maxillary expansion (RME)
      and facial mask (FM). MATERIALS AND METHODS: Twenty-five subjects [10 boys, 15
      girls; mean age at T1 (start of treatment) 9.3+/-1.6 years] with class III
      disharmony were treated with RME and FM therapy followed by fixed appliances. The
      patients were re-evaluated at the end of growth (T2), about 8.5 years after the
      end of the treatment (mean age, 18.6+/-2.0 years). Sixteen subjects with
      untreated class III malocclusion comprised the control group. Mandibular shape
      changes were analysed on the lateral cephalograms of the subjects of both groups
      by means of thin-plate spline (TPS) analysis. Procrustes average mandibular
      configurations were subjected to TPS analysis by means of both cross-sectional
      between-group comparisons at T1 and at T2 and longitudinal within-group
      comparisons. Statistical analysis of shape differences was performed using a
      generalized Goodall F test. RESULTS: In the long term, the treated group
      exhibited a significant upward and forward direction of condylar growth. On the
      contrary, untreated class III subjects showed an upward and backward direction of
      condylar growth associated with a downward and forward deformation of the
      mandibular symphysis. LIMITATIONS: Limitations are related to the small sample
      size of both treated and control groups and to the retrospective nature of the
      study. CONCLUSIONS: Early treatment of class III malocclusion with RME and FM is
      able to produce significant and favourable long-term mandibular shape changes
      characterized by an anterior morphogenetic rotation.

PMID- 24036059
TI  - Melatonin attenuates dexamethasone-induced spatial memory impairment and
      dexamethasone-induced reduction of synaptic protein expressions in the mouse
      brain.
AB  - Chronic stress or prolonged exposure to high levels of glucocorticoid induces
      neuropathological alterations, such as dendritic atrophy of hippocampal or
      cortical neurons. The chronic administration of high doses of dexamethasone
      (DEX), a synthetic glucocorticoid receptor agonist, impairs long-term memory and
      motor coordination, reduces body weight and induces mortality in mice. DEX is
      typically administered clinically for a prolonged period. Therefore, we are
      interested in studying the mechanism by which chronic DEX administration affects
      cognitive function. In this study, we attempted to explore whether chronic DEX
      administration alters the process of memory formation and to determine the
      mechanism underlying the detrimental effect of DEX. The results showed that mice
      treated with DEX for 21 consecutive days had significantly impaired spatial
      memory in the Morris Water Maze task. Mice treated with DEX had prolonged water
      maze performance latencies and spent less time in the target quadrant compared to
      the control group. Furthermore, DEX reduced brain-derived neurotrophic factor
      (BDNF), N-methyl-d-aspartate (NMDA) receptor subunit (NR2A/B), calcium/calmodulin
      dependent protein kinase II (CaMKII) in both the prefrontal cortex and
      hippocampus and synaptophysin in the prefrontal cortex. We also investigated
      whether melatonin, a hormone synthesized in the pineal gland, could protect
      against DEX-induced changes in spatial memory and synaptic plasticity. The
      results showed that mice pretreated with melatonin prior to the DEX treatment had
      shorter escape latencies and remained in the target quadrant longer compared to
      the group only treated with DEX. Melatonin significantly prevented a DEX-induced
      reduction in the expression of NR2A/B, BDNF, CaMKII and synaptophysin. The
      results from the present study demonstrate that melatonin pretreatment prevents
      cognitive impairment caused by DEX. However, the precise mechanism by which
      melatonin affects cognitive function requires further investigation. 

PMID- 24036061
TI  - Localization of the glycine transporter GLYT1 in glutamatergic synaptic vesicles.
AB  - We have previously shown the presence of the glycine transporter GLYT1 in
      glutamatergic terminals of the rat brain. In this study we present
      immunohistochemical and biochemical evidence indicating that GLYT1 is expressed
      not only at the plasma membrane of glutamatergic neurons, but also at synaptic
      vesicles. Confocal microscopy, immunoblots analysis of a highly purified synaptic
      vesicle fraction and immunoisolation of synaptic vesicles with anti-synaptophysin
      antibodies strongly suggested the presence of GLYT1 in synaptic vesicles.
      Moreover, direct observation with the electron microscope of purified vesicles
      immunoreacted with anti-GLYT1 and colloidal gold demonstrated that about 40% of
      the small vesicles of the purified vesicle fraction contained GLYT1. Double
      labeling for GLYT1 and synaptophysin of this vesicular fraction revealed that
      more of ninety percent of them were synaptic vesicles. Moreover, a significant
      part of the GLYT1 containing vesicles (86%) also contained the vesicular
      glutamate transporter vGLUT1, suggesting a functional role of GLYT1 in a
      subpopulation of glutamatergic vesicles. 

PMID- 24036062
TI  - Impact of defoliation on the regrowth capacity and the shoot metabolite profile
      of Plantago lanceolata L.
AB  - After defoliation challenges, plants should invest their resources in a way that
      maximizes their fitness, which may lead to trade-offs in investment in
      physiological versus chemical traits. Thereby, the regrowth capacity of plants
      may highly depend on the type and the severity of defoliation. In the present
      study, we investigated the phenotypic plasticity of Plantago lanceolata L. in
      response to different defoliation events in a comprehensive way, measuring
      various traits. This herbaceous species grows on ruderal sites and typically
      suffers from repeated substantial losses of shoot biomass due to mowing and/or
      herbivory during the growing season. To study treatment-specific effects of
      defoliation on resource allocation and induction of defence responses, plants
      were exposed either to (repeated) mechanical clipping or to herbivory by the
      generalist Grammia incorrupta (Lepidoptera). Next to regrowth and physiological
      leaf traits such as the water content, the specific leaf area and C/N ratios of
      these plants, primary and secondary metabolites in leaves were analyzed with a
      metabolite profiling approach using gas chromatography coupled with mass
      spectrometry. The different defoliation treatments strongly affected the regrowth
      capacity of clipped and herbivore-treated plants, leading to additive changes in
      physiological leaf traits. As a response to the defoliation treatments, clipped
      and herbivore-treated plants reduced mainly carbon-based primary metabolites such
      as sorbitol, and glucose, suggesting that the different defoliation challenges
      similarly limited the ability of carbon fixation. Yet, only in response to
      herbivory but not to clipping, plants induced defence compounds, which indicates
      the importance of treatment-specific responses despite severe resource
      limitations. Overall, the different responses to defoliation by clipping and
      herbivory may reflect allocation constraints and/or adaptive plasticity. 

PMID- 24036060
TI  - Neuroserpin up-regulation in the Alzheimer's disease brain is associated with
      elevated thyroid hormone receptor-beta1 and HuD expression.
AB  - Neuroserpin, the major inhibitor of tissue plasminogen activator (tPA) in brain,
      has been shown to be up-regulated in Alzheimer's disease (AD). Inhibition of tPA
      activity leads to reduced brain levels of plasmin, one of the main enzymes
      responsible for the degradation and clearance of amyloid-beta and its plaques
      from the brain. Thyroid hormone is one of the few factors known to enhance
      expression of neuroserpin in neurons. Thyroid hormone acts on neurons by binding
      to its receptors THR1alpha and THR1beta, which then function in the nucleus to up
      regulate the expression of numerous genes including the RNA-binding protein HuD.
      HuD acts post-transcriptionally to enhance expression of numerous proteins
      including neuroserpin by stabilizing their mRNAs. A series of Alzheimer's disease
      brain tissues were compared to age-matched control brains for their expression of
      neuroserpin, THRbeta1 and HuD by western blotting. Alzheimer's disease brain
      tissues with elevated neuroserpin protein also showed increased expression of
      THRbeta1 and HuD. Pair-wise analyses showed significant correlation p-values
      between neuroserpin, THRbeta1 and HuD levels; suggesting that the up-regulation
      of neuroserpin in Alzheimer's disease brain may result from an activation of the
      thyroid hormone response system in these individuals. These findings provide
      evidence for a potential relationship between thyroid hormone disorders and
      Alzheimer's disease. 

PMID- 24036063
TI  - Anti-fatigue activity of polysaccharides from the fruits of four Tibetan plateau
      indigenous medicinal plants.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The fruits of Hippophae rhamnoides L., Lycium
      barbarum L., Lycium ruthenicum Murr. and Nitraria tangutorum Bobr. are
      traditional medicinal food of Tibetans and used to alleviate fatigue caused by
      oxygen deficiency for thousands of years. The present study focused on exploiting
      natural polysaccharides with remarkable anti-fatigue activity from the four
      Qinghai-Tibet plateau characteristic berries. MATERIALS AND METHODS: The fruits
      of Hippophae rhamnoides, Lycium barbarum, Lycium ruthenicum and Nitraria
      tangutorum were collected from Haixi national municipality of Mongol and Tibetan
      (N 36.32 degrees , E98.11 degrees ; altitude: 3100 m), Qinghai, China. Their
      polysaccharides (HRWP, LBWP, LRWP and NTWP) were isolated by hot-water
      extraction, and purified by DEAE-Cellulose ion-exchange chromatography. The total
      carbohydrate, uronic acid, protein and starch contents of polysaccharides were
      determined by a spectrophotometric method. The molecular weight distributions of
      polysaccharides were determined by gel filtration chromatography. Their
      monosaccharide composition analysis was performed by the method of 1-phenyl-3
      methyl-5-pyrazolone (PMP) pre-column derivatization and RP-HPLC analysis. HRWP,
      LBWP, LRWP and NTWP (50, 100 and 200 mg/kg) were orally administrated to mice
      once daily for 15 days, respectively. Anti-fatigue activity was assessed using
      the forced swim test (FST), and serum biochemical parameters were determined by
      an autoanalyzer and commercially available kits; the body and organs were also
      weighted. RESULT: LBWP, LRWP and NTWP were mainly composed of glucans and some RG
      I pectins, and HRWP was mainly composed of HG-type pectin and some glucans. All
      the four polysaccharides decreased immobility in the FST, and the effects of LBWP
      and NTWP were demonstrated in lower doses compared with HRWP and LRWP. There was
      no significant difference in liver and heart indices between non-treated and
      polysaccharide-treated mice, but the spleen indices were increased in LBWP and
      NTWP (200mg/kg) group. Moreover, the FST-induced reduction in glucose (Glc),
      superoxide dismutase (SOD) and glutathione peroxidase (GPx) and increase in
      creatine phosphokinase (CK), lactic dehydrogenase (LDH), blood urea nitrogen
      (BUN), triglyceride (TG) and malondialdehyde (MDA) levels, all indicators of
      fatigue, were inhibited by HRWP, LBWP, LRWP and NTWP to a certain extent while
      the effects of LBWP and NTWP were much better than that of HRWP and LRWP at the
      same dosage. CONCLUSION: Water-soluble polysaccharides HRWP, LBWP, LRWP and NTWP,
      from the fruits of four Tibetan plateau indigenous berry plants, significantly
      exhibited anti-fatigue activities for the first time, through triglyceride (TG)
      (or fat) mobilization during exercise and protecting corpuscular membrane by
      prevention of lipid oxidation via modifying several enzyme activities. Moreover,
      it is demonstrated that LBWP and NTWP are more potent than HRWP and LRWP, which
      were proposed to be applied in functional foods for anti-fatigue and antioxidant
      potential.

PMID- 24036064
TI  - In vitro characterization of ABC transporters involved in the absorption and
      distribution of liensinine and its analogs.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Lotus plumule, the dried young cotyledon and
      radicle of the Nelumbo nucifera Gaertn. (Fam. Nymphaeaceae) ripe seed, is a
      famous Traditional Chinese Medicine to remove heat from the heart, anchor the
      mind, improve seminal emission, and arrest bleeding for centuries in China.
      Liensinine and its analogs neferine and isoliensinine are the major active
      components in lotus plumule. Aim of the study is to investigate the association
      of liensinine, neferine, and isoliensinine with efflux transporters. MATERIALS
      AND METHODS: Caco-2, MDCK, MDCK-MDR1, and MDCK-MRP2 were used as cell models for
      the transcellular transport and accumulation studies. RESULTS: The results
      obtained in Caco-2 cells suggested that P-glycoprotein (P-gp) might be involved
      in transcellular transport. Cellular accumulation and transport experiments were
      further performed in MDCK-MDR1 cells. GF120918 and cyclosporine A were found to
      completely inhibit the efflux, and the net efflux ratios of these alkaloids
      exhibited saturation over the concentration range. No significant differences in
      liensinine accumulation and transport were observed between MDCK and MDCK-MRP2
      cells. CONCLUSIONS: These results demonstrated that liensinine, neferine, and
      isoliensinine are substrates of P-gp, whereas MRP2 is not involved in the
      transport process, suggesting that P-gp might be responsible for the absorption
      and distribution of the 3 alkaloids.

PMID- 24036065
TI  - Effects of perinatal ethinyl estradiol exposure in male and female Wistar rats.
AB  - Perinatal exposure to endocrine disrupting chemicals with estrogenic activity can
      adversely affect reproductive development, but few studies evaluating estrogen
      sensitive endpoints have been performed in Wistar rats. Therefore, time-mated
      Wistar rats (n=10) were gavaged during gestation and lactation with 0, 5, 15 or
      50MUg/kg bw/day of ethinyl estradiol. This potent estrogen was found to induce an
      increased number of nipples and reduced ovary weight in female offspring.
      Malformations of female genitalia were found in young as well as adult offspring,
      as an increased AGD was seen at birth and a deeper urethral slit length was seen
      in adulthood. In prepubertal male offspring, estrogen-regulated gene expression
      in ventral prostate was increased dose-dependently and a decreased ventral
      prostate weight was seen at 15MUg/kg. Female external sexual characteristics and
      prostate development were found to be targets for exposure to estrogenic
      compounds and may be of interest in studies on estrogenic environmental
      compounds. 

PMID- 24036066
TI  - Fabrication of high-density collagen fibril matrix gels by renaturation of triple
      helix collagen from gelatin.
AB  - Collagen-based 3-D hydrogels often lack sufficient mechanical strength for tissue
      engineering. We developed a method for fabrication of high-density collagen
      fibril matrix (CFM) gels from concentrated solutions of uncleaved gelatin (UCG).
      Denatured random-coil UCG exhibited more rapid and efficient renaturation into
      collagen triple-helix than cleaved gelatin (CG) over a broad range of setting
      temperatures. The UCG solution formed opaque gels with high-density reconstituted
      collagen fibrils at 28-32  degrees C and transparent gels similar to CG at <25 
      degrees C. The unique gelation properties of UCG enabled the encapsulation of
      cultured cells in CFM of high solid volume (>5%) and elasticity (1.28 +/- 0.15
      kPa at 5% and 4.82 +/- 0.38 kPa at 8%) with minimal cell loss. The elastic
      modulus of these gels was higher than that of conventional CFM containing 0.5%
      collagen. High-strength CFM may provide more durable hydrogels for tissue
      engineering and regenerative medicine.

PMID- 24036068
TI  - Participant profiles according to recruitment source in a large Web-based
      prospective study: experience from the Nutrinet-Sante study.
AB  - BACKGROUND: Interest in Internet-based epidemiologic research is growing given
      the logistic and cost advantages. Cohort recruitment to maximally diversify the
      sociodemographic profiles of participants, however, remains a contentious issue.
      OBJECTIVE: The aim of the study was to characterize the sociodemographic profiles
      according to the recruitment mode of adult volunteers enrolled in a Web-based
      cohort. METHODS: The French NutriNet-Sante Web-based cohort was launched in 2009.
      Recruitment is ongoing and largely relies on recurrent multimedia campaigns. One
      month after enrollment, participants are asked how they learned about the study
      (eg, general newscast or a health program on television, radio newscast,
      newspaper articles, Internet, personal advice, leaflet/flyers) The
      sociodemographic profiles of participants recruited through operative
      communication channels (radio, print media, Internet, advice) were compared with
      the profiles of those informed through television by using polytomous logistic
      regression. RESULTS: Among the 88,238 participants enrolled through the end of
      2011, 30,401 (34.45%), 16,751 (18.98%), and 14,309 (16.22%) learned about the
      study from television, Internet, and radio newscasts, respectively.
      Sociodemographic profiles were various, with 14,541 (16.5%) aged >=60 years,
      20,166 (22.9%) aged <30 years, 27,766 (32.1%) without postsecondary education,
      15,397 (19.7%) with household income <?1200/month, and 8258 (10.6%) with
      household income ?3700/month. Compared to employed individuals, unemployed and
      retired participants were less likely to be informed about the study through
      other sources than through television (adjusted ORs 0.56-0.83, P<.001).
      Participants reporting up to secondary education were also less likely to have
      learned about the study through radio newscasts, newspaper articles, Internet,
      and advice than through television (adjusted ORs 0.60-0.77, P<.001). CONCLUSIONS:
      Television broadcasts appear to permit the recruitment of e-cohort participants
      with diverse sociodemographic backgrounds, including socioeconomically
      disadvantaged individuals who are usually difficult to reach and retain in long
      term epidemiologic studies. These findings could inform future Web-based studies
      regarding the development of promising targeted or general population recruitment
      strategies.

PMID- 24036067
TI  - Pax3 synergizes with Gli2 and Zic1 in transactivating the Myf5 epaxial somite
      enhancer.
AB  - Both Glis, the downstream effectors of hedgehog signaling, and Zic transcription
      factors are required for Myf5 expression in the epaxial somite. Here we
      demonstrate a novel synergistic interaction between members of both families and
      Pax3, a paired-domain transcription factor that is essential for both myogenesis
      and neural crest development. We show that Pax3 synergizes with both Gli2 and
      Zic1 in transactivating the Myf5 epaxial somite (ES) enhancer in concert with the
      Myf5 promoter. This synergy is dependent on conserved functional domains of the
      proteins, as well as on a novel homeodomain motif in the Myf5 promoter and the
      essential Gli motif in the ES enhancer. Importantly, overexpression of Zic1 and
      Pax3 in the 10T1/2 mesodermal cell model results in enrichment of these factors
      at the endogenous Myf5 locus and induction of Myf5 expression. In our previous
      work, we showed that by enhancing nuclear translocation of Gli factors, Zics
      provide spatiotemporal patterning for Gli family members in the epaxial induction
      of Myf5 expression. Our current study indicates a complementary mechanism in
      which association with DNA-bound Pax3 strengthens the ability of both Zic1 and
      Gli2 to transactivate Myf5 in the epaxial somite. 

PMID- 24036069
TI  - Multiphase modelling of the influence of fluid flow and chemical concentration on
      tissue growth in a hollow fibre membrane bioreactor.
AB  - A 2D model is developed for fluid flow, mass transport and cell distribution in a
      hollow fibre membrane bioreactor. The geometry of the modelling region is
      simplified by excluding the exit ports at either end and focusing on the upper
      half of the central section of the bioreactor. Cells are seeded on a porous
      scaffold throughout the extracapillary space (ECS), and fluid pumped through the
      bioreactor via the lumen inlet and/or exit ports. In the fibre lumen and porous
      fibre wall, flow is described using Stokes and Darcy governing equations,
      respectively, while in the ECS porous mixture theory is used to model the cells,
      culture medium and scaffold. Reaction-advection-diffusion equations govern the
      concentration of a solute of interest in each region. The governing equations are
      reduced by exploiting the small aspect ratio of the bioreactor. This yields a
      coupled system for the cell volume fraction, solute concentration and ECS water
      pressure which is solved numerically for a variety of experimentally relevant
      case studies. The model is used to identify different regimes of cell behaviour,
      and results indicate how the flow rate can be controlled experimentally to
      generate a uniform cell distribution under regimes relevant to nutrient- and/or
      chemotactic-driven behaviours. 

PMID- 24036070
TI  - Outcome of redo surgical aortic valve replacement in patients 80 years and older:
      results from the Multicenter RECORD Initiative.
AB  - BACKGROUND: Octogenarians undergoing surgical aortic valve replacement (AVR)
      after prior cardiac surgery are expected to be at high risk of adverse events.
      This finding has recently popularized transcatheter AVR in this cohort. METHODS:
      This multicenter study includes 744 patients (99 were 80 years or older) who
      underwent surgical AVR after prior cardiac surgery. The outcome of octogenarians
      was compared with younger patients in the entire cohort and in a propensity score
      matched population. RESULTS: Octogenarians and younger patients had similar
      immediate outcome (in-hospital mortality, 3.0% versus 5.9%; p=0.34; stroke, 5.1%
      versus 6.7%; p=0.66; dialysis, 9.1% versus 6.5%; p=0.34), as confirmed also in 84
      propensity score-matched pairs. Octogenarians and younger patients had similar
      late survival (5-year survival, 83.1% versus 78.0%; p=0.68; propensity score
      adjusted relative risk [RR], 0.23; 95% confidence interval [CI], 0.59 to 1.88).
      Octogenarians and younger patients had similar freedom from heart failure
      episodes (at 5 years, 84.5% versus 89.2%; p=0.311; propensity score-adjusted RR,
      1.37; 95% CI, 0.62 to 3.04) and from reoperation (at 5 years, 94.9% versus 97.9%;
      p=0.51; propensity score-adjusted RR, 1.93; 95% CI, 0.35 to 10.56). However,
      octogenarians had poorer freedom from late stroke (at 5 years, 89.8% versus
      97.5%; p=0.016; propensity score-adjusted RR, 6.137; 95% CI, 1.776 to 21.208) and
      peripheral thromboembolism (at 5 years, 90.0% versus 98.2%; p=0.003; propensity
      score-adjusted RR, 4.00; 95% CI, 1.07 to 15.00). CONCLUSIONS: Octogenarians
      undergoing surgical AVR after prior cardiac surgery have similar immediate
      postoperative outcome as younger patients, and their 5-year outcome is excellent.
      These data suggest that indications to undergo transcatheter AVR should not rely
      only on coexistence of advanced age and history of prior cardiac surgery.

PMID- 24036071
TI  - Comparison of the detection of HPV-16, 18, 31, 33, and 45 by type-specific DNA-
      and E6/E7 mRNA-based assays of HPV DNA positive women with abnormal Pap smears.
AB  - This study compares the type-specific human papillomavirus (HPV) DNA test with
      E6/E7 mRNA detection assay because of their importance in cervical cancer
      screening programs. A total of 105 women with positive high-risk Hybrid Capture 2
      or Abbott RealTime High Risk HPV screening test and an abnormal cervical Pap
      smear were enrolled in the study. HPV typing was performed by multiplex real-time
      PCR (HPV High Risk Typing Real-TM test). HPV-16, 18, 31, 33, and 45 E6/E7 mRNAs
      were determined by type-specific real-time NASBA assay (NucliSENS EasyQ HPV
      v1.1). Infections caused by HPV-16, 18, 31, 33, and 45 types increased with
      severity of cervical cytology (p=0.008). Global positivity of five HPV E6/E7
      mRNAs was lower than DNA positivity within women with atypical squamous cells of
      undetermined significance (p=0.016; p=0.008). High agreement of the tests was
      found in the groups of women with low-grade (p=1.000; p=0.063) and high-grade
      squamous intraepithelial lesion (p=0.250; p=0.125). Type-specific agreement of
      both diagnostic approaches was high regardless of cytology. Based on the found
      differences between HPV-16, 18, 31, 33, and 45 E6/E7 mRNA and DNA positivity,
      further study is needed to test the role of mRNA testing in the triage of women
      with atypical squamous cells of undetermined significance in Pap smear.

PMID- 24036072
TI  - Allele-specific polymerase chain reaction for detection of a mutation in the
      relax circular DNA and the covalently closed circular DNA of hepatitis B virus.
AB  - The relax circle DNA (rcDNA) sequence and the covalently closed circle DNA
      (cccDNA) sequence in hepatitis B virus (HBV) are crucial regions for HBV
      infections. To analyze mutations in rcDNA and cccDNA, DNA sequencing is often
      used, although it is time-consuming and expensive. Herein, we report a simple,
      economic, albeit accurate allele-specific polymerase chain reaction (AS-PCR) to
      detect mutations in these regions of HBV. This method can be extensively used to
      screen for mutations at specific positions of HBV genome. 

PMID- 24036073
TI  - Humanized-VH/VHH that inhibit HCV replication by interfering with the virus
      helicase activity.
AB  - NS3 helicase is a pivotal enzyme involved in the early and late phases of
      hepatitis C virus (HCV) replication. The primary sequence and tertiary structure
      of this virus enzyme differ from human helicase to a certain extent; thus this
      virus protein has potential as a novel anti-HCV target. In this study,
      recombinant C-terminal NS3 protein of HCV genotype 3a with endowed helicase
      activity was produced and used as antigen by selecting VH/V(H)H display phage
      clones from an established humanized-camel single domain antibody library that
      bound specifically to HCV helicase. The VH/V(H)H derived from phage transfected
      Escherichia coli clones were linked molecularly to a cell penetrating peptide,
      i.e., penetratin (PEN). The cell penetrable VH/V(H)H (transbodies) could reduce
      the amounts of the HCV RNA released into the cell culture fluid and inside Huh7
      cells infected with pJFH1 replicon with a greater effect on the former compared
      to the latter. Regions and residues of the helicase bound by the transbodies were
      determined by phage mimotope searching and multiple alignments as well as
      homology modeling and molecular docking. The epitope of one transbody (PEN
      V(H)H9) encompassed residues 588RLKPTLHGPTPLLYRLGA605 of the domain 3 necessary
      for helicase activity while another transbody (PEN-VH59) interacted with the
      areas covering the phenylalanine loop and arginine clamp of the domain 2 which
      are important for the proper folding of the enzyme as well as nucleic acid
      substrate binding. Although the molecular mechanisms of the prototypic
      transbodies on NS3 helicase need further investigation, these transbodies have
      high potential as novel, safe and mutation tolerable anti-HCV agents.

PMID- 24036074
TI  - Evaluation of rapid and simple techniques for the enrichment of viruses prior to
      metagenomic virus discovery.
AB  - The discovery of new or divergent viruses using metagenomics and high-throughput
      sequencing has become more commonplace. The preparation of a sample is known to
      have an effect on the representation of virus sequences within the metagenomic
      dataset yet comparatively little attention has been given to this. Physical
      enrichment techniques are often applied to samples to increase the number of
      viral sequences and therefore enhance the probability of detection. With the
      exception of virus ecology studies, there is a paucity of information available
      to researchers on the type of sample preparation required for a viral metagenomic
      study that seeks to identify an aetiological virus in an animal or human
      diagnostic sample. A review of published virus discovery studies revealed the
      most commonly used enrichment methods, that were usually quick and simple to
      implement, namely low-speed centrifugation, filtration, nuclease-treatment (or
      combinations of these) which have been routinely used but often without
      justification. These were applied to a simple and well-characterised artificial
      sample composed of bacterial and human cells, as well as DNA (adenovirus) and RNA
      viruses (influenza A and human enterovirus), being either non-enveloped capsid or
      enveloped viruses. The effect of the enrichment method was assessed by both
      quantitative real-time PCR and metagenomic analysis that incorporated an
      amplification step. Reductions in the absolute quantities of bacteria and human
      cells were observed for each method as determined by qPCR, but the relative
      abundance of viral sequences in the metagenomic dataset remained largely
      unchanged. A 3-step method of centrifugation, filtration and nuclease-treatment
      showed the greatest increase in the proportion of viral sequences. This study
      provides a starting point for the selection of a purification method in future
      virus discovery studies, and highlights the need for more data to validate the
      effect of enrichment methods on different sample types, amplification,
      bioinformatics approaches and sequencing platforms. This study also highlights
      the potential risks that may attend selection of a virus enrichment method
      without any consideration for the sample type being investigated. 

PMID- 24036075
TI  - Comparative evaluation of commercially available manual and automated nucleic
      acid extraction methods for rotavirus RNA detection in stools.
AB  - Rotaviruses are a major cause of viral gastroenteritis in children. For accurate
      and sensitive detection of rotavirus RNA from stool samples by reverse
      transcription-polymerase chain reaction (RT-PCR), the extraction process must be
      robust. However, some extraction methods may not remove the strong RT-PCR
      inhibitors known to be present in stool samples. The objective of this study was
      to evaluate and compare the performance of six extraction methods used commonly
      for extraction of rotavirus RNA from stool, which have never been formally
      evaluated: the MagNA Pure Compact, KingFisher Flex and NucliSENS easyMAG
      instruments, the NucliSENS miniMAG semi-automated system, and two manual
      purification kits, the QIAamp Viral RNA kit and a modified RNaid kit. Using each
      method, total nucleic acid or RNA was extracted from eight rotavirus-positive
      stool samples with enzyme immunoassay optical density (EIA OD) values ranging
      from 0.176 to 3.098. Extracts prepared using the MagNA Pure Compact instrument
      yielded the most consistent results by qRT-PCR and conventional RT-PCR. When
      extracts prepared from a dilution series were extracted by the 6 methods and
      tested, rotavirus RNA was detected in all samples by qRT-PCR but by conventional
      RT-PCR testing, only the MagNA Pure Compact and KingFisher Flex extracts were
      positive in all cases. RT-PCR inhibitors were detected in extracts produced with
      the QIAamp Viral RNA Mini kit. The findings of this study should prove useful for
      selection of extraction methods to be incorporated into future rotavirus
      detection and genotyping protocols.

PMID- 24036076
TI  - Development of a Usutu virus specific real-time reverse transcription PCR assay
      based on sequenced strains from Africa and Europe.
AB  - Usutu virus (USUV) has been isolated in several African and European countries
      mainly from mosquitoes and birds. However, previous benign and two recent severe
      cases of human infections point out the need of a tool for the identification of
      USUV in human samples. A published real-time reverse transcription (RT) PCR assay
      for the detection of USUV in human blood or cerebrospinal fluid does not take
      into account the genetic variability of USUV in different geographic regions.
      Therefore, this article presents a quantitative real-time RT-PCR assay based on
      sequences from Europe and Africa. Primers and probe were designed in conserved
      regions among USUV strains that differed from closely related flaviviruses. The
      specificity of the assay was investigated by testing 16 other flaviviruses
      circulating in Africa. The sensitivity was determined by testing serial dilutions
      of virus and RNA standard. Intra- and inter-assay coefficients of variation were
      evaluated by 10 reactions in a same and in different assays, respectively. The
      assay provides high analytical specificity for USUV and detection limits of
      1.2pfu/reaction for virus dilutions in L-15 medium or human serum and 60
      copies/reaction for the RNA standard. The assay needs to be evaluated in a
      clinical context and integrated in standard diagnosis of flaviviral diseases. 

PMID- 24036077
TI  - Transcriptional coactivator CIITA, a functional homolog of TAF1, has kinase
      activity.
AB  - The Major Histocompatibility Complex (MHC) class II transactivator (CIITA)
      mediates activated immune responses and its deficiency results in the Type II
      Bare Lymphocyte Syndrome. CIITA is a transcriptional co-activator that regulates
      gamma-interferon-activated transcription of MHC class I and class II genes. It is
      also a functional homolog of TAF1, a component of the general transcription
      factor complex TFIID. TAF1 and CIITA both possess intrinsic acetyltransferase
      (AT) activity that is required for transcription initiation. In response to
      induction by gamma-interferon, CIITA and it's AT activity bypass the requirement
      for TAF1 AT activity. TAF1 also has kinase activity that is essential for its
      function. However, no similar activity has been identified for CIITA thus far.
      Here we report that CIITA, like TAF1, is a serine-threonine kinase. Its substrate
      specificity parallels, but does not duplicate, that of TAF1 in phosphorylating
      the TFIID component TAF7, the RAP74 subunit of the general transcription factor
      TFIIF and histone H2B. Like TAF1, CIITA autophosphorylates, affecting its
      interaction with TAF7. Additionally, CIITA phosphorylates histone H2B at Ser36, a
      target of TAF1 that is required for transcription during cell cycle progression
      and stress response. However, unlike TAF1, CIITA also phosphorylates all the
      other histones. The identification of this novel kinase activity of CIITA further
      clarifies its role as a functional homolog of TAF1 which may operate during
      stress and gamma-IFN activated MHC gene transcription. 

PMID- 24036078
TI  - Correlation of biological activity with computationally derived structural
      features from transmembrane hetero-dimers of HIV-1 Vpu with host factors.
AB  - Vpu is an 81 amino acid type I integral membrane protein encoded by human
      immunodeficiency virus type 1 (HIV-1). It is identified to support viral release
      by potentially forming ion and substrate conducting channels and by modulating
      the function of host factors. The focus is on the interaction of the
      transmembrane domains of Vpu with those of host factors using a combination of
      molecular dynamics simulations and docking approach. Binding poses and adopted
      tilt angles of the dimers are analyzed and correlated with experimentally derived
      activity data from literature. Vpu activity is driven by dimerization with the
      host protein via its alanine rim Ala-8/11/15/19. Tight binding is shown by an
      almost parallel alignment of the helices in the dimers. Less parallel alignment
      is proposed to correlate with lower activity. This article is part of a Special
      Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking. 

PMID- 24036079
TI  - Improving the stability and function of purified ABCB1 and ABCA4: the influence
      of membrane lipids.
AB  - ATP Binding Cassette (ABC) transporters play prominent roles in numerous cellular
      processes and many have been implicated in human diseases. Unfortunately,
      detailed mechanistic information on the majority of ABC transporters has not yet
      been elucidated. The slow rate of progress of molecular and high resolution
      structural studies may be attributed to the difficulty in the investigation of
      integral membrane proteins. These difficulties include the expression of
      functional, non-aggregated protein in heterologous systems. Furthermore, the
      extraction of membrane proteins from source material remains a major bottle-neck
      in the process since there are relatively few guidelines for selection of an
      appropriate detergent to achieve optimal extraction. Whilst affinity tag
      strategies have simplified the purification of membrane proteins; many challenges
      remain. For example, the chromatographic process and associated steps can rapidly
      lead to functional inactivation, random aggregation, or even precipitation of the
      target protein. Furthermore, optimisation of high yield and purity, does not
      guarantee successful structure determination. Based on this series of potential
      issues, any investigation into structure-function of membrane proteins requires a
      systematic evaluation of preparation quality. In particular, the evaluation
      should focus on function, homogeneity and mono-dispersity. The present
      investigation provides a detailed assessment of the quality of purified ATP
      Binding Cassette (ABC) transporters; namely ABCB1 (P-gp) and ABCA4 (ABCR). A
      number of suggestions are provided to facilitate the production of functional,
      homogeneous and mono-disperse preparations using the insect cell expression
      system. Finally, the ABCA4 samples have been used to provide structural insights
      into this essential photo-receptor cell protein. 

PMID- 24036080
TI  - Rubber particle proteins, HbREF and HbSRPP, show different interactions with
      model membranes.
AB  - The biomembrane surrounding rubber particles from the hevea latex is well known
      for its content of numerous allergen proteins. HbREF (Hevb1) and HbSRPP (Hevb3)
      are major components, linked on rubber particles, and they have been shown to be
      involved in rubber synthesis or quality (mass regulation), but their exact
      function is still to be determined. In this study we highlighted the different
      modes of interactions of both recombinant proteins with various membrane models
      (lipid monolayers, liposomes or supported bilayers, and multilamellar vesicles)
      to mimic the latex particle membrane. We combined various biophysical methods
      (polarization-modulation-infrared reflection-adsorption spectroscopy (PM
      IRRAS)/ellipsometry, attenuated-total reflectance Fourier-transform infrared (ATR
      FTIR), solid-state nuclear magnetic resonance (NMR), plasmon waveguide resonance
      (PWR), fluorescence spectroscopy) to elucidate their interactions. Small rubber
      particle protein (SRPP) shows less affinity than rubber elongation factor (REF)
      for the membranes but displays a kind of "covering" effect on the lipid
      headgroups without disturbing the membrane integrity. Its structure is conserved
      in the presence of lipids. Contrarily, REF demonstrates higher membrane affinity
      with changes in its aggregation properties, the amyloid nature of REF, which we
      previously reported, is not favored in the presence of lipids. REF binds and
      inserts into membranes. The membrane integrity is highly perturbed, and we
      suspect that REF is even able to remove lipids from the membrane leading to the
      formation of mixed micelles. These two homologous proteins show affinity to all
      membrane models tested but neatly differ in their interacting features. This
      could imply differential roles on the surface of rubber particles. 

PMID- 24036081
TI  - Reversing metabolic diseases through diabetes surgery: do the proximal gut and
      related hormones play key roles in glucose homeostasis?

PMID- 24036082
TI  - Serum levels of cardiac troponin I in patients with status epilepticus and
      healthy cardiovascular system.
AB  - BACKGROUND AND AIMS: Status epilepticus (SE) is accompanied by acute and intense
      activation of the sympathetic nervous system, which might result in myocyte
      damage. However, there is insufficient evidence to assess cardiac biomarkers in
      SE patients. As a highly specific and sensitive biomarker of acute myocardial
      infarction, serum concentration of cardiac troponin I (cTnI) has been assessed in
      this study in a sample of SE patients without evidence of previous cardiovascular
      diseases. METHODS: In this analytical cross-sectional study, a total number of 30
      patients with SE and no history of baseline cardiovascular disorders, aged
      between 12 and 60 years have been evaluated. Baseline, demographic
      characteristics and laboratory measurements including cTnI, creatine kinase (CPK)
      and CPK-MB were recorded for all of patients. cTnI was quantified using ELISA
      method with the precision of 0.01 ng/mL. RESULTS: All cases had a cardiac
      troponin level <0.01 ng/mL except for one 60- year-old female with a history of
      seizure 3 years prior. The last seizure was 60 days prior and the patient had a
      reported cTnI level as 0.04 ng/mL, within normal limits. The mean serum levels of
      CPK and CK-MB were 202.20 (SD = 14.46) MUg/l and 14.54 (SD = 1.49) ng/mL,
      respectively. CONCLUSIONS: This investigation is one of the few to evaluate serum
      concentration of cTnI in generalized convulsive SE patients where no detectable
      elevation was observed in serum concentration of cTnI following SE episode.
      However, it is very important to take into account that all recruited SE patients
      included in this study had a healthy cardiovascular system.

PMID- 24036083
TI  - Electrocardiographic screening of 1-month-old infants for identifying prolonged
      QT intervals.
AB  - BACKGROUND: Neonatal electrocardiographic screening is used to screen infants
      with prolonged QT intervals, as previously shown in whites. However, this
      procedure needs to be confirmed in other ethnic groups. METHODS AND RESULTS: In 8
      areas in Japan, an ECG was recorded in 4285 infants at 1-month medical checkup. A
      prospective study showed that a provisional criterion of QTc>=470 ms was
      appropriate for infants. To assess the validity of the criterion, all infants
      with a QTc between 460 and 470 ms were followed up. Five infants had a QTc>=470
      ms. Four infants were diagnosed with prolonged QT intervals from follow-up ECGs.
      Four infants showed no symptoms and did not have a family history of long-QT
      syndrome. Two infants showed progressive prolongation of QT intervals, and
      medication was started. Genetic testing was performed in 3 of 4 infants with
      prolonged QT intervals, and it revealed a KCNH2 mutation (3065 delT, L1021fs+34X)
      in 1 infant. One infant with a QTc>=470 ms and 2 infants with a QTc between 460
      and 470 ms showed a decline in their QTc values during follow-up. The study
      screened another infant with Wolff-Parkinson-White syndrome who was diagnosed
      with noncompaction before symptoms appeared. CONCLUSIONS: Neonatal
      electrocardiographic screening can identify infants likely to be affected by long
      QT syndrome in the Japanese population, as already shown in whites. This
      screening may also be useful in identifying other important cardiac diseases.

PMID- 24036085
TI  - Evolution of ventricular tachycardia and its electrophysiological substrate early
      after myocardial infarction: an ovine model.
AB  - BACKGROUND: Sudden arrhythmic death after myocardial infarction (MI) is most
      frequent in the first month. Early programmed ventricular stimulation (within 1
      week) post-MI has been able to identify long-term ventricular tachycardia (VT)
      occurrence. We aimed to determine the timing of development and stabilization of
      VT circuits after MI and how the evolution of the underlying substrate differs
      with VT inducibility. METHODS AND RESULTS: MIs were induced in 36 sheep. The 21
      survivors underwent serial electroanatomic mapping and programmed ventricular
      stimulation. Animals were classified as VTpos (inducible VT) or VTneg
      (noninducible VT) at day 8. Forty-three percent of MI survivors were VTpos on day
      8 (9/21), and all remained inducible on day 100 with 1.5 (1.0-2.0) and 1.0 (1.0
      2.0) morphologies per animal on days 8 and 100, respectively. Twelve-lead
      electrocardiogram matched in 15 of 19 VTs between days 8 and 100. The earliest
      presystolic ventricular activations during VT circuits were in similar locations
      at the 2 time points. The 12 VTneg animals remained noninducible on day 100.
      There was no difference in voltage or velocity substrate with time or
      inducibility. The area with fractionated signals increased with time and VT
      inducibility. VTpos animals had more linear regions of slowed conduction forming
      conducting channels. CONCLUSIONS: The inducibility and earliest presystolic
      endocardial activation sites of VT as well as voltage and velocity substrate on
      day 8 predicted those on day 100 postinfarct, indicating early formation and
      stabilization of the arrhythmogenic substrate. VT inducibility was influenced by
      the distribution of conducting channels and increased complex fractionated
      signals.

PMID- 24036084
TI  - Unfolded protein response regulates cardiac sodium current in systolic human
      heart failure.
AB  - BACKGROUND: Human heart failure (HF) increases alternative mRNA splicing of the
      type V, voltage-gated cardiac Na+ channel alpha-subunit (SCN5A), generating
      variants encoding truncated, nonfunctional channels that are trapped in the
      endoplasmic reticulum. In this work, we tested whether truncated Na+ channels
      activate the unfolded protein response (UPR), contributing to SCN5A electric
      remodeling in HF. METHODS AND RESULTS: UPR and SCN5A were analyzed in human
      ventricular systolic HF tissue samples and human induced pluripotent stem cell
      derived cardiomyocytes (hiPSC-CMs). Cells were exposed to angiotensin II (AngII)
      and hypoxia, known activators of abnormal SCN5A mRNA splicing, or were induced to
      overexpress SCN5A variants. UPR effectors, protein kinase R-like ER kinase
      (PERK), calreticulin, and CHOP, were increased in human HF tissues. Induction of
      SCN5A variants with AngII or hypoxia or the expression of exogenous variants
      induced the UPR with concomitant downregulation of Na+ current. PERK activation
      destabilized SCN5A and, surprisingly, Kv4.3 channel mRNAs but not transient
      receptor potential cation channel M7 (TRPM7) channel mRNA. PERK inhibition
      prevented the loss of full-length SCN5A and Kv4.3 mRNA levels resulting from
      expressing Na+ channel mRNA splice variants. CONCLUSIONS: UPR can be initiated by
      Na+ channel mRNA splice variants and is involved in the reduction of cardiac Na+
      current during human HF. Because the effect is not entirely specific to the SCN5A
      transcript, the UPR may play an important role in downregulation of multiple
      cardiac genes in HF.

PMID- 24036086
TI  - Effect of freeze-drying, cryoprotectants and storage conditions on the stability
      of secondary structure of insulin-loaded solid lipid nanoparticles.
AB  - This study aims to monitor the secondary structure behaviour of insulin when it
      is encapsulated into solid lipid nanoparticles (SLN), under the influence of
      several critical processing parameters. Insulin was used as a therapeutic protein
      model. Physicochemical properties of insulin-loaded SLN (Ins-SLN) were assessed,
      with special focus on the insulin secondary structure after its encapsulation
      into SLN and after freeze-drying using different cryoprotectants (glucose,
      fructose and sorbitol). Additionally, a 6-month stability study was performed to
      evaluate the maintenance of insulin secondary structure over time at different
      storage conditions (4  degrees C/60% RH, 25  degrees C/60% RH, 40  degrees C/75%
      RH). Ins-SLN were successfully produced with a mean and narrow particle size
      around 400 nm, zeta potential around -13 mV, an insulin association efficiency of
      84%. Physical-chemical properties of SLN were maintained after freeze-drying.
      FTIR results showed that encapsulated insulin maintained a native-like structure
      in a degree of similarity around 92% after production, and 84% after freeze
      drying. After 6 months, freeze-dried Ins-SLN without cryoprotectant stored at 40 
      degrees C/75% RH presented the same degree of structure preservation and
      morphology. Results revealed that insulin structure can be significantly
      protected by SLN matrix itself, without a cryoprotectant agent, even using a non
      optimized freeze-drying process, and under the harsher storage conditions.
      Multivariable experimental settled the process parameters to fit with the desired
      product quality attributes regarding protein and nanoparticle stability.

PMID- 24036087
TI  - Permeability and lipid organization of a novel psoriasis stratum corneum
      substitute.
AB  - Lipids in the uppermost layer of the skin, the stratum corneum (SC), play an
      important role in the skin barrier properties. The main lipid classes are
      ceramides, cholesterol and free fatty acids. In previous studies a stratum
      corneum substitute (SCS) was developed, solely prepared from the SC lipids. The
      SCS mimics the lipid barrier properties of SC very closely. The present study
      aimed to design a psoriasis SCS (PS-SCS) mimicking several aspects of the lipid
      composition in SC from psoriasis patients. This PS-SCS showed a different lipid
      organization than SCS. The main differences were a reduced presence of an
      orthorhombic packing and an increased level of crystalline cholesterol. These
      changes resulted in lower flux of hydrocortisone across PS-SCS than across SCS
      and SC, which was most likely attributed to the higher level of phase separated
      crystalline cholesterol in PS-SCS. As propylene glycol (PG) is often used in
      dermatological formulations, in subsequent studies the interaction of PG with SC
      and SCS membranes was also investigated. These studies revealed that PG increased
      the permeability of hydrocortisone, mainly by selectively extracting cholesterol
      from SCS membranes and SC. This may play an important role in the penetration
      enhancing effect of PG. 

PMID- 24036088
TI  - Assessing treatments used to reduce rumination and/or worry: a systematic review.
AB  - Perseverative cognitions such as rumination and worry are key components of
      mental illnesses such as depression and anxiety. Given the frequent comorbidity
      of conditions in which rumination and worry are present, it is possible that they
      are underpinned by the same cognitive process. Furthermore, rumination and worry
      appear to be part of a causal chain that can lead to long-term health
      consequences, including cardiovascular disease and other chronic conditions. It
      is important therefore to understand what interventions may be useful in reducing
      their incidence. This systematic review aimed to assess treatments used to reduce
      worry and/or rumination. As we were interested in understanding the current
      treatment landscape, we limited our search from 2002 to 2012. Nineteen studies
      were included in the review and were assessed for methodological quality and
      treatment integrity. Results suggested that mindfulness-based and cognitive
      behavioural interventions may be effective in the reduction of both rumination
      and worry; with both Internet-delivered and face-to-face delivered formats
      useful. More broadly, it appears that treatments in which participants are
      encouraged to change their thinking style, or to disengage from emotional
      response to rumination and/or worry (e.g., through mindful techniques), could be
      helpful. Implications for treatment and avenues for future research are
      discussed. 

PMID- 24036090
TI  - Molecular structure, vibrational spectra, NMR and UV spectral analysis of
      sulfamethoxazole.
AB  - Fourier transform infrared (FTIR) and FT-Raman spectra have been recorded and
      extensive spectroscopic investigations have been carried out on Sulfamethoxazole
      (SMX). The structural and spectroscopic data of the molecule in the ground state
      were calculated by using density functional method (DFT) using 6-31G(d,p) basis
      set. The vibrational frequencies were calculated and scaled values were compared
      with experimental FT-IR and FT-Raman spectra. The observed and calculated
      frequencies are found to be in good agreement. (13)C and (1)H NMR chemical shifts
      results were given and are in agreement with the corresponding experimental
      values. The theoretically constructed FT-IR and FT-Raman spectra exactly coincide
      with experimental one. Besides, NBO, molecular electrostatic potential (MEP),
      frontier molecular orbitals (FMO) analysis were investigated using theoretical
      calculations. 

PMID- 24036089
TI  - Use of alcohol protective behavioral strategies among college students: a
      critical review.
AB  - Protective behavioral strategies (PBS) are specific behaviors one can utilize to
      minimize the harmful consequences of alcohol consumption. Recently, there has
      been an increasing amount of interest in use of PBS among college students,
      especially as an intervention target. The purpose of the present comprehensive
      review of the PBS literature was to examine the measurement of PBS and summarize
      the quantitative relationships between PBS use and other variables. The review
      found inconsistency across studies in terms of how the use of PBS is
      operationalized and found only two PBS measures with good psychometric properties
      that have been replicated. Although several antecedents to PBS use were
      identified, most were only examined in single studies. Moderators of the
      predictive effects of PBS use on outcomes have similarly suffered from lack of
      replication in the literature. Of all 62 published reports reviewed, 80% reported
      only cross-sectional data, which is unfortunate given that PBS use may change
      over time and in different contexts. In addition, only two attempted to minimize
      potential recall biases associated with retrospective assessment of PBS use, and
      only two used an approach that allowed the examination of both within-subject and
      between-subject effects. In terms of the gaps in the literature, there is a
      dearth of longitudinal studies of PBS use, especially intensive longitudinal
      studies, which are integral to identifying more specifically how, when, and for
      whom use of PBS can be protective. 

PMID- 24036091
TI  - Recovery of valuable metals from electroplating sludge with reducing additives
      via vitrification.
AB  - In this study, vitrification was applied to treat Ni-Cu electroplating sludge.
      The sludge was mixed with additives (limestone:cullet = 4:6) and then heated to
      1450  degrees C. The cooled product could be separated into slag and ingot. An
      atomic absorption spectrometer was used to determine the metal levels of
      specimens and toxicity characteristic leaching procedure (TCLP) tests, whereas
      the crystalline and surface characteristics were examined using quantitative X
      ray diffraction (XRD) analysis and scanning electron microscopy, respectively.
      With a glassy structure, the slag was mainly composed of Ca, Si, and Mg. The TCLP
      results of slags met the Taiwan regulated standards, suggesting that slag can be
      used for recycling purposes. With the aid of additives, the crystalline phase of
      slag was transformed form CaMgSiO4 into CsSiO3. The ingots were mainly composed
      of Ni (563,000-693,800 mg/kg), Cu (79,900-87,400 mg/kg), and Fe (35,000-43,600
      mg/kg) (target metals) due the gravity separation during vitrification. At
      appropriate additives/sludge ratios (>0.2), >95% of target metals gathered in the
      ingot as a recoverable form (Ni-Fe alloy). The high Ni level of slag suggests
      that the ingot can be used as the raw materials for smelters or the additives for
      steel making. Therefore, the vitrification approach of this study is a promising
      technology to recover valuable metals from Ni-Cu electroplating sludge. 

PMID- 24036092
TI  - Check dam and polyacrylamide performance under simulated stormwater runoff.
AB  - High levels of turbidity and fine suspended sediments are often found in
      stormwater discharges from construction sites even when best management practices
      (BMPs) for sediment control are in place. This study evaluated turbidity
      reduction by three check dam types: 1) rock check dam representing a standard
      BMP, 2) excelsior wattle representing a fiber check dam (FCD), and 3) rock check
      dam wrapped with excelsior erosion control blanket (rock + excelsior ECB)
      representing an alternative FCD. Three check dams (all same type) were installed
      in a lined, 24-m ditch on a 5-7% slope and three consecutive simulated stormwater
      flows were run in the ditch. Additional tests were performed by adding granular
      polyacrylamide (PAM) on the check dams in the same manner using two sediment
      sources differing in clay content. Without PAM treatment, significantly higher
      effluent turbidity (>900 nephelometric turbidity units (NTU)) exited the ditch
      with rock check dams than with excelsior wattles or rock + excelsior ECBs (<440
      NTU). The extent of sediment deposition between the check dam types was in the
      order of excelsior wattle > rock + excelsior ECB > rock check dam, indicating
      better water pooling behind the wattle. The PAM treatment reduced turbidity
      substantially (>75% relative to no PAM treatment) for all check dam types and it
      was very effective in excelsior wattles (<57 NTU) and rock + excelsior ECBs (<90
      NTU) even during the third storm event. This study demonstrates that the passive
      treatment of runoff with PAM on FCDs (or rock + excelsior ECB) in construction
      site ditches can be very effective for sediment retention and turbidity
      reduction. 

PMID- 24036093
TI  - Mapping potential carbon and timber losses from hurricanes using a decision tree
      and ecosystem services driver model.
AB  - Information on the effect of direct drivers such as hurricanes on ecosystem
      services is relevant to landowners and policy makers due to predicted effects
      from climate change. We identified forest damage risk zones due to hurricanes and
      estimated the potential loss of 2 key ecosystem services: aboveground carbon
      storage and timber volume. Using land cover, plot-level forest inventory data,
      the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model, and
      a decision tree-based framework; we determined potential damage to subtropical
      forests from hurricanes in the Lower Suwannee River (LS) and Pensacola Bay (PB)
      watersheds in Florida, US. We used biophysical factors identified in previous
      studies as being influential in forest damage in our decision tree and hurricane
      wind risk maps. Results show that 31% and 0.5% of the total aboveground carbon
      storage in the LS and PB, respectively was located in high forest damage risk
      (HR) zones. Overall 15% and 0.7% of the total timber net volume in the LS and PB,
      respectively, was in HR zones. This model can also be used for identifying timber
      salvage areas, developing ecosystem service provision and management scenarios,
      and assessing the effect of other drivers on ecosystem services and goods. 

PMID- 24036094
TI  - Extant forest plantations as a potential bridge between social needs and
      ecological management: a comparative case study analysis.
AB  - In the face of global deforestation, there is a challenge to balance the
      management of areas of high conservation concern and social interests. As a
      response to the growing human-environment interface and the use of forests for
      subsistence, plantations became a management tool to provide for wood harvesting
      during the 1970s. Some plantations were subsequently protected from harvest as
      conservation of all forests increased. Plantations that are now illegal to
      harvest can cause local animosities toward forest protection to increase and may
      also result in concentrated harvesting impacts on surrounding natural forests. In
      this article, we analyzed case studies of plantations from El Salvador and Niger.
      By utilizing distinctly disparate case studies, commonalities between the two can
      illuminate possible management lessons. In the comparison of El Salvador and
      Niger forest plantations we found the following commonalities: utilizing
      plantations for sustainable harvest has the to potential to reduce animosity
      between managers and stakeholders; plantations can serve as a risk-averse testing
      ground for novel managerial practices; and the sustainable harvest of plantations
      can reduce deforestation and impacts on biodiversity in natural remnant forests.
      We argue that extant plantations currently under illegal harvesting legislation
      could become the epicenters of social and ecological conservation through a
      management shift to sustainable harvesting. By focusing on these relics, managers
      could work with stakeholders to change unduly burdening restrictions and promote
      cooperation between conservationists and local populations. 

PMID- 24036095
TI  - Threats to Mediterranean rangelands: a case study based on the views of citizens
      in the Viotia prefecture, Greece.
AB  - Rangelands in Greece constitute a very important natural resource as they occupy
      40% of the total surface. Not only is their forage production essential for the
      development of extensive livestock farming, but also they play a key role in
      outdoor recreational activities, protection from erosion, provision of water
      supplies and biodiversity conservation. However, land use changes, inappropriate
      management and wildfires threaten their existence. The research was conducted
      among the citizens of Viotia prefecture, an area close to Athens, Greece, using
      personal interviews with a structured questionnaire in 2008. The aim was to
      record citizens' opinions regarding the threats to rangelands. The results
      suggest that the main threats as perceived by the respondents, are land use
      changes especially for urban development, and wildfires. The application of
      cluster analysis highlighted the differentiation among the respondents in ranking
      these threats. The more ecologically aware citizens recognised that
      mismanagement, abandonment and agriculture also threaten rangelands. These
      threats can have a considerable impact on the lives of the local people. Policy
      makers and managers should take the opinions of local citizens into
      consideration, and engage them in decision making so that sustainable management
      policies could be applied. 

PMID- 24036096
TI  - Fuel reduction at a Spanish heathland by prescribed fire and mechanical
      shredding: effects on seedling emergence.
AB  - Traditional heathland burning has declined in Spain, leading to fuel accumulation
      and fuel reduction treatments have become common for severe wildfire hazard
      reduction. These methods need to maintain the botanical composition of those
      shrub communities. Prescribed fire has been widely used in the past, but we need
      to compare mechanical fuel reduction with prescribed fire because it is easier
      and safer to carry out in a wide range of weather conditions. This information
      could be particularly useful in flammable ecosystems all over the world where
      traditional anthropogenic burning has declined. In this study, we compared the
      effects of prescribed burning and mechanical shredding on the seedling emergence
      and its relation to the mature vegetation in a fire-prone heathland dominated by
      Erica australis L. and Pterospartum tridentatum (L.) Willk., in Galicia (NW
      Spain). We combined a greenhouse experiment with periodic field inventories of
      seedling emergence. In the greenhouse study, the seedling emergence was
      significantly higher in the soil samples after burning (383 seedlings m(-2)) than
      in samples before burning (242 seedlings m(-2)). In contrast, there was no
      significant difference in seedling density before and after mechanical shredding
      (243 compared with 261 seedlings m(-2)). Also, the number of seedlings that
      emerged after burning was significantly higher than that emerged after mechanical
      shredding. The maximum temperatures at the soil organic layer surface during
      burning were significantly and positively related to the density of Halimium
      lasianthum ssp. alyssoides and P. tridentatum seedlings. In the field study, the
      observed seedling density was very low both after prescribed burning and
      mechanical shredding. There was a high degree of similarity between emerged
      seedlings and mature vegetation in both the treated and in the untreated soils,
      which was probably a consequence of the dominance of resprouting species. Some
      consequences for the management of these shrublands are also discussed. 

PMID- 24036097
TI  - Three-dimensional geological modelling of anthropogenic deposits at small urban
      sites: a case study from Sheepcote Valley, Brighton, UK.
AB  - Improvements in computing speed and capacity and the increasing collection and
      digitisation of geological data now allow geoscientists to produce meaningful 3D
      spatial models of the shallow subsurface in many large urban areas, to predict
      ground conditions and reduce risk and uncertainty in urban planning. It is not
      yet clear how useful this 3D modelling approach is at smaller urban scales, where
      poorly characterised anthropogenic deposits (artificial/made ground and fill)
      form the dominant subsurface material and where the availability of borehole and
      other geological data is less comprehensive. This is important as it is these
      smaller urban sites, with complex site history, which frequently form the focus
      of urban regeneration and redevelopment schemes. This paper examines the extent
      to which the 3D modelling approach previously utilised at large urban scales can
      be extended to smaller less well-characterised urban sites, using a historic
      landfill site in Sheepcote Valley, Brighton, UK as a case study. Two 3D models
      were generated and compared using GSI3DTM software, one using borehole data only,
      one combining borehole data with local geological maps and results from a desk
      study (involving collation of available site data, including ground contour
      plans). These models clearly delimit the overall subsurface geology at the site,
      and allow visualisation and modelling of the anthropogenic deposits present.
      Shallow geophysical data collected from the site partially validate the 3D
      modelled data, and can improve GSI3DTM outputs where boundaries of anthropogenic
      deposits may not be clearly defined by surface, contour or borehole data.
      Attribution of geotechnical and geochemical properties to the 3D model is
      problematic without intrusive investigations and sampling. However, combining
      available borehole data, shallow geophysical methods and site histories may allow
      attribution of generic fill properties, and consequent reduction of urban
      development risk and uncertainty. 

PMID- 24036098
TI  - Combined mathematical modelling and experimentation to predict polymersome uptake
      by oral cancer cells.
AB  - This study is motivated by understanding and controlling the key physical
      properties underlying internalisation of nano drug delivery. We consider the
      internalisation of specific nanometre size delivery vehicles, comprised of self
      assembling amphiphilic block copolymers, called polymersomes that have the
      potential to specifically deliver anticancer therapeutics to tumour cells. The
      possible benefits of targeted polymersome drug delivery include reduced off
      target toxic effects in healthy tissue and increased drug uptake by diseased
      tissue. Through a combination of in vitro experimentation and mathematical
      modelling, we develop a validated model of nanoparticle uptake by cells via the
      clathrin-mediated endocytotic pathway, incorporating receptor binding, clustering
      and recycling. The model predicts how the characteristics of receptor targeting,
      and the size and concentration of polymersomes alter uptake by tumour cells. The
      number of receptors per cell was identified as being the dominant mechanism
      accounting for the difference between cell types in polymersome uptake rate. FROM
      THE CLINICAL EDITOR: This article reports on a validated model developed through
      a combination of in vitro experimentation and mathematical modeling of
      nanoparticle uptake by cells via the clathrin-mediated endocytotic pathway. The
      model incorporates receptor binding, clustering, and recycling and predicts how
      the characteristics of receptor targeting, the size and concentration alter
      polymersome uptake by cancer cells.

PMID- 24036099
TI  - Improved stability and immunological potential of tetanus toxoid containing
      surface engineered bilosomes following oral administration.
AB  - The present study was designed with the objective to investigate the stability
      and potential of glucomannan-modified bilosomes (GM-bilosomes) in eliciting
      immune response following oral administration. GM-bilosomes exhibited desired
      quality attributes simultaneously maintaining the chemical and conformation
      stability of the tetanus toxoid (TT) entrapped in to freeze dried formulations.
      The GM-bilosomes exhibited excellent stability in different simulated biological
      fluids and sustained release profile up to 24 h. GM-bilosomes elicited
      significantly higher (P<0.05) systemic immune response (serum IgG level) as
      compared to bilosomes, niosomes and alum adsorbed TT administered through oral
      route. More importantly, GM-bilosomes were found capable of inducing mucosal
      immune response, i.e. sIgA titre in salivary and intestinal secretions as well as
      cell mediated immune response (IL-2 and IFN-gamma levels in spleen homogenate)
      which was not induced by i.m. TT, the conventional route of immunization.
      Conclusively, GM-bilosomes could be considered as a promising carrier and
      adjuvant system for oral mucosal immunization. FROM THE CLINICAL EDITOR: This
      team reports on the development and effects of a glucomannan-modified bilosome as
      an oral vaccine vector, using tetanus toxoid in the experiments. These GM
      bilosomes not only elicited significantly higher systemic immune response as
      compared to bilosomes, niosomes and alum adsorbed orally administered TT, but
      also demonstrated mucosal immune response induction as well as cell mediated
      immune responses, which were not induced by the conventional route of
      immunization.

PMID- 24036100
TI  - Non-tumor mast cells cultured in vitro on a honeycomb-like structured film
      proliferate with multinucleated formation.
AB  - Mast cells are released from bone marrow into the circulatory system as immature
      precursors and differentiate upon their arrival at diverse organs and tissues.
      Because mast cell functions can be altered in these tissues, we propose that mast
      cells are sensitive to their surrounding microenvironment. To examine the
      morphological responses of mast cells, we cultured a proliferative mouse non
      tumor cell line of mast cells (NCL-2 cells) on a honeycomb-like structured
      polystyrene film (HCF) representing a microenvironmental scaffold. In this study,
      the NCL-2 cells cultured on the HCF proliferated without apoptosis. Furthermore,
      NCL-2 cells cultured on 3- and 5-MUm HCFs exhibited multinuclear formation. These
      observations of different NCL-2 cell morphologies and proliferation rates on HCF
      scaffolds with different hole sizes suggest that mast cells undertake specific
      proliferative shapes depending on the surrounding microenviroment. Moreover, HCFs
      may lead to the regulation of mast cell differentiation. FROM THE CLINICAL
      EDITOR: This team reports on the development of a honeycomb-like structured film
      to study mast cell differentiation of non-cancerous origin, demonstrating that
      different microenvironments provided by different honeycomb hole sizes determine
      the morphology of the differentiated cells.

PMID- 24036101
TI  - Lysine residues of IGF-I are substrates for transglutaminases and modulate
      downstream IGF-I signalling.
AB  - Numerous studies have reported associations between IGF-I and other extra
      cellular matrix (ECM) proteins, including fibronectin (FN), integrins, IGF
      binding proteins (IGFBPs) and through IGFBPs, with vitronectin (VN).
      Nevertheless, the precise nature and mechanisms of these interactions are still
      being characterised. In this paper, we discuss transglutaminases (TGases) as a
      constituent of the ECM and provide evidence for the first time that IGF-I is a
      lysine (K)-donor substrate to TGases. When IGF-I was incubated with an alpha-2
      plasmin inhibitor-derived Q peptide in the presence of tissue transglutaminase
      (TG2), an IGF-I:Q peptide cross-linked species was detected using Western
      immunoblotting and confirmed by mass spectrometry. Similar findings were observed
      in the presence of Factor XIIIa (FXIIIa) TGase. To identify the precise location
      of this K-donor TGase site/s on IGF-I, all the three IGF-I K-sites, individually
      and collectively (K27, K65 and K68), were substituted to arginine (R) using site
      directed mutagenesis. Incubation of these K->R IGF-I analogues with Q peptide in
      the presence of TG2 or FXIIIa resulted in the absence of cross-linking in IGF-I
      analogues bearing arginine substitution at site 68. This established that K68
      within the IGF-I D-domain was the principal K-donor site to TGases. We further
      annotated the functional significance of these K->R IGF-I analogues on IGF-I
      mediated actions. IGF-I analogues with K->R substitution within the D-domain at
      K65 and K68 hindered migration of MCF-7 breast carcinoma cells and
      correspondingly reduced PI3-K/AKT activation. Therefore, this study also provides
      first insights into a possible functional role of the previously uncharacterised
      IGF-I D-domain. 

PMID- 24036102
TI  - Identification of voltage-gated K(+) channel beta 2 (Kvbeta2) subunit as a novel
      interaction partner of the pain transducer Transient Receptor Potential Vanilloid
      1 channel (TRPV1).
AB  - The Transient Receptor Potential Vanilloid 1 (TRPV1, vanilloid receptor 1) ion
      channel plays a key role in the perception of thermal and inflammatory pain,
      however, its molecular environment in dorsal root ganglia (DRG) is largely
      unexplored. Utilizing a panel of sequence-directed antibodies against TRPV1
      protein and mouse DRG membranes, the channel complex from mouse DRG was detergent
      solubilized, isolated by immunoprecipitation and subsequently analyzed by mass
      spectrometry. A number of potential TRPV1 interaction partners were identified,
      among them cytoskeletal proteins, signal transduction molecules, and established
      ion channel subunits. Based on stringent specificity criteria, the voltage-gated
      K(+) channel beta 2 subunit (Kvbeta2), an accessory subunit of voltage-gated K(+)
      channels, was identified of being associated with native TRPV1 channels. Reverse
      co-immunoprecipitation and antibody co-staining experiments confirmed
      TRPV1/Kvbeta2 association. Biotinylation assays in the presence of Kvbeta2
      demonstrated increased cell surface expression levels of TRPV1, while patch-clamp
      experiments resulted in a significant increase of TRPV1 sensitivity to capsaicin.
      Our work shows, for the first time, the association of a Kvbeta subunit with
      TRPV1 channels, and suggests that such interaction may play a role in TRPV1
      channel trafficking to the plasma membrane. 

PMID- 24036103
TI  - Increased response time of primed associates following an "episodic" hypnotic
      amnesia suggestion: a case of unconscious volition.
AB  - Following a hypnotic amnesia suggestion, highly hypnotically suggestible subjects
      may experience amnesia for events. Is there a failure to retrieve the material
      concerned from autobiographical (episodic) memory, or is it retrieved but blocked
      from consciousness? Highly hypnotically suggestible subjects produced free
      associates to a list of concrete nouns. They were then given an amnesia
      suggestion for that episode followed by another free association list, which
      included 15 critical words that had been previously presented. If episodic
      retrieval for the first trial had been blocked, the responses on the second trial
      should still have been at least as fast as for the first trial. With semantic
      priming, they should be faster. In fact, they were on average half a second
      slower. This suggests that the material had been retrieved but blocked from
      consciousness. A goal-oriented information processing framework is outlined to
      interpret these and related data. 

PMID- 24036104
TI  - The complex interplay of iron metabolism, reactive oxygen species, and reactive
      nitrogen species: insights into the potential of various iron therapies to induce
      oxidative and nitrosative stress.
AB  - Production of minute concentrations of superoxide (O2(*-)) and nitrogen monoxide
      (nitric oxide, NO*) plays important roles in several aspects of cellular
      signaling and metabolic regulation. However, in an inflammatory environment, the
      concentrations of these radicals can drastically increase and the antioxidant
      defenses may become overwhelmed. Thus, biological damage may occur owing to redox
      imbalance-a condition called oxidative and/or nitrosative stress. A complex
      interplay exists between iron metabolism, O2(*-), hydrogen peroxide (H2O2), and
      NO*. Iron is involved in both the formation and the scavenging of these species.
      Iron deficiency (anemia) (ID(A)) is associated with oxidative stress, but its
      role in the induction of nitrosative stress is largely unclear. Moreover, oral as
      well as intravenous (iv) iron preparations used for the treatment of ID(A) may
      also induce oxidative and/or nitrosative stress. Oral administration of ferrous
      salts may lead to high transferrin saturation levels and, thus, formation of non
      transferrin-bound iron, a potentially toxic form of iron with a propensity to
      induce oxidative stress. One of the factors that determine the likelihood of
      oxidative and nitrosative stress induced upon administration of an iv iron
      complex is the amount of labile (or weakly-bound) iron present in the complex.
      Stable dextran-based iron complexes used for iv therapy, although they contain
      only negligible amounts of labile iron, can induce oxidative and/or nitrosative
      stress through so far unknown mechanisms. In this review, after summarizing the
      main features of iron metabolism and its complex interplay with O2(*-), H2O2,
      NO*, and other more reactive compounds derived from these species, the potential
      of various iron therapies to induce oxidative and nitrosative stress is discussed
      and possible underlying mechanisms are proposed. Understanding the mechanisms, by
      which various iron formulations may induce oxidative and nitrosative stress, will
      help us develop better tolerated and more efficient therapies for various
      dysfunctions of iron metabolism.

PMID- 24036105
TI  - Involvement of superoxide dismutase isoenzymes and their genetic variants in
      progression of and higher susceptibility to vitiligo.
AB  - Oxidative stress has been implicated as the initial triggering event in vitiligo
      pathogenesis leading to melanocyte destruction. Here, we report a significant
      increase in oxidative stress in vitiligo patients as evidenced by high lipid
      peroxidation levels suggesting an imbalance in the antioxidant enzyme system as
      reported in our previous studies. This study examined the role of the enzymatic
      antioxidant SOD, which converts the pro-oxidant superoxide into H2O2, in vitiligo
      pathogenesis. The activity of three isoforms of SOD, i.e., SOD1, SOD2, and SOD3,
      was significantly higher in vitiligo patients. To identify the underlying
      mechanism for the increase in activities of SOD isoforms, we explored the SOD1,
      SOD2, and SOD3 genes for their genetic variations and transcript levels. The SOD2
      Thr58Ile (rs35289490) and Leu84Phe (rs11575993) polymorphisms were significantly
      associated with vitiligo patients, and the Val16Ala (rs4880) polymorphism was
      associated with active vitiligo patients. Interestingly, SOD2 activity was
      contributed by these polymorphisms along with its increase in transcript levels
      in patients. SOD3 activity was associated with the Arg213Gly (rs8192291)
      polymorphism. The SOD3 transcript levels were also increased in patients, which
      might contribute to the increased SOD3 activity. However, we could not establish
      the genotype-phenotype correlation for SOD1 as we could not detect any novel or
      reported SNPs in SOD1. In addition, both transcript and protein levels of SOD1
      were unchanged between patients and controls, though SOD1 activity was increased
      in patients. Activities of SOD isoforms also correlated with progression of the
      disease as the activity was higher in active cases of vitiligo compared to stable
      cases. Here, we report that SOD2 and SOD3 polymorphisms may be genetic risk
      factors for susceptibility and progression of vitiligo and hence the genetic
      makeup of an individual may form a basis for the effective treatment of the
      disease. Overall, our results suggest that increased activity of SOD isoforms
      under the influence of genetic factors may lead to accumulation of H2O2 in
      cytoplasmic, mitochondrial, and extracellular compartments resulting in oxidative
      damage to the melanocytes. 

PMID- 24036106
TI  - Hemodynamic evaluation of severe tricuspid regurgitation.

PMID- 24036107
TI  - Additive antidepressant-like effects of fasting with imipramine via modulation of
      5-HT2 receptors in the mice.
AB  - Recently, studies show that intermittent fasting and caloric restriction may
      improve symptoms of depression. However, there is little scientific evidence
      regarding the literature on the antidepressant-like effects of acute fasting. The
      present study aims to investigate the antidepressant-like effects and its
      influence on brain levels of the transcription factor cAMP response element
      binding protein (CREB) and its phosphorylated form (p-CREB) in different time
      periods of fasting mice. Furthermore, the additive antidepressant-like effects of
      fasting with imipramine and the possible involvement of the 5-HT2 receptors were
      examined. In the present study 9h, but not 3h and 18h of fasting significantly
      reduced immobility time in the forced swimming test (FST) without alteration in
      locomotor activity in the open field test. 9h fasting also enhanced the ratio of
      p-CREB/CREB in the frontal cortex and hippocampus. Co-administration of 9h of
      fasting and imipramine (30mg/kg, i.p) produced the additive antidepressant-like
      effects in the FST and increased the ratio of p-CREB/CREB. Meanwhile, the
      additive effects were partially reversed by treatment with a 5-HT2A/2C receptor
      agonist, (+/-)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI)
      (5mg/kg, s.c). Furthermore, the antidepressant-like effects of 9h fasting was
      also blocked by DOI compared to the non-fasting control group. Serum
      corticosterone level, but not 5-HT and noradrenaline, was significantly increased
      in a time-dependent manner following different time periods of fasting. Taken
      together, these results suggest that acute fasting produces antidepressant-like
      effects via enhancement of the p-CREB/CREB ratio, and additive antidepressant
      like effects of fasting with imipramine may be related to modulating 5-HT2
      receptors. 

PMID- 24036108
TI  - Effects of the sazetidine-a family of compounds on the body temperature in
      wildtype, nicotinic receptor beta2-/- and alpha7-/- mice.
AB  - Nicotine elicits hypothermic responses in rodents. This effect appears to be
      related to nicotinic receptor desensitization because sazetidine-A, an
      alpha4beta2 nicotinic receptor desensitizing agent, produces marked hypothermia
      and potentiates nicotine-induced hypothermia in mice. To determine the
      specificity of sazetidine-A induced hypothermia to beta2 subunit-containing
      nicotinic receptors, we tested its efficacy in beta2 knockout (beta2(-/-)) mice.
      These effects were compared with wildtype (WT) and alpha7 knockout (alpha7(-/-))
      mice. Confirming our earlier results, sazetidine-A elicited a pronounced and long
      lasting hypothermia in WT mice. In comparison, sazetidine-A induced a much
      attenuated and shorter hypothermic response in beta2(-/-) mice. This indicates
      that the greater proportion of sazetidine-A induced hypothermia is mediated via
      actions on beta2-containing nicotinic receptors, while a smaller component of
      hypothermia induced by sazetidine-A is mediated by non-beta2 receptors. Similar
      to WT mice, alpha7(-/-) mice showed the full extent of the sazetidine-A effect,
      suggesting that the hypothermia produced by sazetidine-A did not depend on
      actions on alpha7 nicotinic receptor subtype. Three other novel nicotinic
      receptor desensitizing agents derived from sazetidine-A, triazetidine-O, VMY-2-95
      and YL-1-127 also produced hypothermia in WT and alpha7(-/-) mice. Furthermore,
      unlike sazetidine-A, triazetidine-O and YL-1-127 did not show any hint of a
      hypothermic effect in beta2(-/-) mice. VMY-2-95 like sazetidine-A did show a
      residual hypothermic effect in the beta2(-/-) mice. These studies show that the
      hypothermic effects of sazetidine-A and the related compound VMY-2-95 are mainly
      mediated by nicotinic receptors containing beta2 subunit, but that a small
      component of the effect is apparently mediated by non-beta2 containing receptors.

PMID- 24036109
TI  - Phorbaketal A inhibits adipogenic differentiation through the suppression of
      PPARgamma-mediated gene transcription by TAZ.
AB  - Obesity causes several metabolic diseases, including diabetes. Adipogenic
      differentiation is an important event for fat formation in obesity. Natural
      compounds that inhibit adipogenic differentiation are frequently screened to
      develop therapeutic drugs for treating obesity. Here we investigated the effects
      of phorbaketal A, a natural marine compound, on adipogenic differentiation of
      mesenchymal stem cells. Phorbaketal A significantly inhibited adipogenic
      differentiation as indicated by less fat droplets and decreased expression of
      adipogenic marker genes. The expression of TAZ (transcriptional coactivator with
      PDZ-binding motif), an inhibitor of adipogenic differentiation, significantly
      increased during adipogenic differentiation in the presence of phorbaketal A.
      Phorbaketal A increased the interaction of TAZ and PPARgamma to suppress
      PPARgamma (peroxisome proliferator-activated receptor gamma) target gene
      expression. TAZ-depleted cells showed higher adipogenic potential than that of
      control cells even in the presence of phorbaketal A. During cellular signaling
      induced by phorbaketal A, ERK (extracellular signal-regulated kinase) played an
      important role in adipogenic suppression; an inhibitor of ERK blocked phorbaketal
      A-induced adipogenic suppression. Thus, the results show that phorbaketal A
      inhibits adipocyte differentiation through TAZ. 

PMID- 24036110
TI  - beta-Adrenergic receptors activate exchange protein directly activated by cAMP
      (Epac), translocate Munc13-1, and enhance the Rab3A-RIM1alpha interaction to
      potentiate glutamate release at cerebrocortical nerve terminals.
AB  - The adenylyl cyclase activator forskolin facilitates synaptic transmission
      presynaptically via cAMP-dependent protein kinase (PKA). In addition, cAMP also
      increases glutamate release via PKA-independent mechanisms, although the
      downstream presynaptic targets remain largely unknown. Here, we describe the
      isolation of a PKA-independent component of glutamate release in cerebrocortical
      nerve terminals after blocking Na(+) channels with tetrodotoxin. We found that 8
      pCPT-2'-O-Me-cAMP, a specific activator of the exchange protein directly
      activated by cAMP (Epac), mimicked and occluded forskolin-induced potentiation of
      glutamate release. This Epac-mediated increase in glutamate release was dependent
      on phospholipase C, and it increased the hydrolysis of phosphatidylinositol 4,5
      bisphosphate. Moreover, the potentiation of glutamate release by Epac was
      independent of protein kinase C, although it was attenuated by the diacylglycerol
      binding site antagonist calphostin C. Epac activation translocated the active
      zone protein Munc13-1 from soluble to particulate fractions; it increased the
      association between Rab3A and RIM1alpha and redistributed synaptic vesicles
      closer to the presynaptic membrane. Furthermore, these responses were mimicked by
      the beta-adrenergic receptor (betaAR) agonist isoproterenol, consistent with the
      immunoelectron microscopy and immunocytochemical data demonstrating presynaptic
      expression of betaARs in a subset of glutamatergic synapses in the cerebral
      cortex. Based on these findings, we conclude that betaARs couple to a
      cAMP/Epac/PLC/Munc13/Rab3/RIM-dependent pathway to enhance glutamate release at
      cerebrocortical nerve terminals. 

PMID- 24036111
TI  - Phosphorylation and mRNA splicing of collapsin response mediator protein-2
      determine inhibition of rho-associated protein kinase (ROCK) II function in
      carcinoma cell migration and invasion.
AB  - The Rho-associated protein kinases (ROCK I and II) are central regulators of
      important cellular processes such as migration and invasion downstream of the GTP
      Rho. Recently, we reported collapsin response mediator protein (CRMP)-2 as an
      endogenous ROCK II inhibitor. To reveal how the CRMP-2-ROCK II interaction is
      controlled, we further mapped the ROCK II interaction site of CRMP-2 and examined
      whether phosphorylation states of CRMP-2 affected the interaction. Here, we show
      that an N-terminal fragment of the long CRMP-2 splice variant (CRMP-2L) alone
      binds ROCK II and inhibits colon carcinoma cell migration and invasion.
      Furthermore, the interaction of CRMP-2 and ROCK II is partially regulated by
      glycogen synthase kinase (GSK)-3 phosphorylation of CRMP-2, downstream of PI3K.
      Inhibition of PI3K reduced interaction of CRMP-2 with ROCK II, an effect rescued
      by simultaneous inhibition of GSK3. Inhibition of PI3K also reduced
      colocalization of ROCK II and CRMP-2 at the cell periphery in human breast
      carcinoma cells. Mimicking GSK3 phosphorylation of CRMP-2 significantly reduced
      CRMP-2 binding of recombinant full-length and catalytic domain of ROCK II. These
      data implicate GSK3 in the regulation of ROCK II-CRMP-2 interactions. Using
      phosphorylation-mimetic and -resistant CRMP-2L constructs, it was revealed that
      phosphorylation of CRMP-2L negatively regulates its inhibitory function in ROCK
      dependent haptotactic cell migration, as well as invasion of human colon
      carcinoma cells. Collectively, the presented data show that CRMP-2-dependent
      regulation of ROCK II activity is mediated through interaction of the CRMP-2L N
      terminus with the ROCK II catalytic domain as well as by GSK3-dependent
      phosphorylation of CRMP-2. 

PMID- 24036112
TI  - Insulin activates RSK (p90 ribosomal S6 kinase) to trigger a new negative
      feedback loop that regulates insulin signaling for glucose metabolism.
AB  - We previously demonstrated that the mTORC1/S6K1 pathway is activated by insulin
      and nutrient overload (e.g. amino acids (AA)), which leads to the inhibition of
      the PI3K/Akt pathway via the inhibitory serine phosphorylation of IRS-1, notably
      on serine 1101 (Ser-1101). However, even in the absence of AA, insulin can still
      promote IRS-1 Ser-1101 phosphorylation by other kinases that remain to be fully
      characterized. Here, we describe a new negative regulator of IRS-1, the p90
      ribosomal S6 kinase (RSK). Computational analyses revealed that Ser-1101 within
      IRS-1 falls into the consensus motif of RSK. Moreover, recombinant RSK
      phosphorylated IRS-1 C-terminal fragment on Ser-1101, which was prevented by
      mutations of this site or when a kinase-inactive mutant of RSK was used. Using
      antibodies directed toward the phosphorylation sites located in the activation
      segment of RSK (Ser-221 or Ser-380), we found that insulin activates RSK in L6
      myocytes in the absence of AA overload. Inhibition of RSK using either the
      pharmacological inhibitor BI-D1870 or after adenoviral expression of a dominant
      negative RSK1 mutant (RSK1-DN) showed that RSK selectively phosphorylates IRS-1
      on Ser-1101. Accordingly, expression of the RSK1-DN mutant in L6 myocytes and FAO
      hepatic cells improved insulin action on glucose uptake and glucose production,
      respectively. Furthermore, RSK1 inhibition prevented insulin resistance in L6
      myocytes chronically exposed to high glucose and high insulin. These results show
      that RSK is a novel regulator of insulin signaling and glucose metabolism and a
      potential mediator of insulin resistance, notably through the negative
      phosphorylation of IRS-1 on Ser-1101. 

PMID- 24036113
TI  - Bovine lactoferricin-induced anti-inflammation is, in part, via up-regulation of
      interleukin-11 by secondary activation of STAT3 in human articular cartilage.
AB  - Bovine lactoferricin (LfcinB), a multifunctional peptide, was recently
      demonstrated to be anti-catabolic and anti-inflammatory in human articular
      cartilage. LfcinB blocks IL-1-mediated proteoglycan depletion, matrix-degrading
      enzyme expression, and pro-inflammatory mediator induction. LfcinB selectively
      activates ERK1/2, p38 (but not JNK), and Akt signaling. However, the relationship
      between these pathways and LfcinB target genes has never been explored. In this
      study, we uncovered the remarkable ability of LfcinB in the induction of an anti
      inflammatory cytokine, IL-11. LfcinB binds to cell surface heparan sulfate to
      initiate ERK1/2 signaling and activate AP-1 complexes composed of c-Fos and JunD,
      which transactivate the IL-11 gene. The induced IL-11 functions as an anti
      inflammatory and chondroprotective cytokine in articular chondrocytes. Our data
      show that IL-11 directly attenuates IL-1-mediated catabolic and inflammatory
      processes ex vivo and in vitro. Moreover, IL-11 activates STAT3 signaling pathway
      to critically up-regulate TIMP-1 expression, as a consecutive secondary cellular
      response after IL-11 induction by LfcinB-ERK-AP-1 axis in human adult articular
      chondrocytes. The pathological relevance of IL-11 signaling to osteoarthritis is
      evidenced by significant down-regulation of its cognate receptor expression in
      osteoarthritic chondrocytes. Together, our results suggest a two-step mechanism,
      whereby LfcinB induces TIMP-1 through an IL-11-dependent pathway involving
      transcription factor AP-1 and STAT3. 

PMID- 24036114
TI  - Two sides of MGP null arterial disease: chondrogenic lesions dependent on
      transglutaminase 2 and elastin fragmentation associated with induction of
      adipsin.
AB  - Mutations in matrix Gla protein (MGP) have been correlated with vascular
      calcification. In the mouse model, MGP null vascular disease presents as
      calcifying cartilaginous lesions and mineral deposition along elastin lamellae
      (elastocalcinosis). Here we examined the mechanisms underlying both of these
      manifestations. Genetic ablation of enzyme transglutaminase 2 (TG2) in Mgp(-/-)
      mice dramatically reduced the size of cartilaginous lesions in the aortic media,
      attenuated calcium accrual more than 2-fold, and doubled longevity as compared
      with control Mgp(-/-) animals. Nonetheless, the Mgp(-/-);Tgm2(-/-) mice still
      died prematurely as compared with wild-type and retained the elastocalcinosis
      phenotype. This pathology in Mgp(-/-) animals was developmentally preceded by
      extensive fragmentation of elastic lamellae and associated with elevated serine
      elastase activity in aortic tissue and vascular smooth muscle cells. Systematic
      gene expression analysis followed by an immunoprecipitation study identified
      adipsin as the major elastase that is induced in the Mgp(-/-) vascular smooth
      muscle even in the TG2 null background. These results reveal a central role for
      TG2 in chondrogenic transformation of vascular smooth muscle and implicate
      adipsin in elastin fragmentation and ensuing elastocalcinosis. The importance of
      elastin calcification in MGP null vascular disease is highlighted by significant
      residual vascular calcification and mortality in Mgp(-/-);Tgm2(-/-) mice with
      reduced cartilaginous lesions. Our studies identify two potential therapeutic
      targets in vascular calcification associated with MGP dysfunction and emphasize
      the need for a comprehensive approach to this multifaceted disorder. 

PMID- 24036115
TI  - The lutheran/basal cell adhesion molecule promotes tumor cell migration by
      modulating integrin-mediated cell attachment to laminin-511 protein.
AB  - Cell-matrix interactions are critical for tumor cell migration. Lutheran (Lu),
      also known as basal cell adhesion molecule (B-CAM), competes with integrins for
      binding to laminin alpha5, a subunit of LM-511, a major component of basement
      membranes. Here we show that the preferential binding of Lu/B-CAM to laminin
      alpha5 promotes tumor cell migration. The attachment of Lu/B-CAM transfectants to
      LM-511 was slightly weaker than that of control cells, and this was because Lu/B
      CAM disturbed integrin binding to laminin alpha5. Lu/B-CAM induced a spindle cell
      shape with pseudopods and promoted cell migration on LM-511. In addition,
      blocking with an anti-Lu/B-CAM antibody led to a flat cell shape and inhibited
      migration on LM-511, similar to the effects of an activating integrin beta1
      antibody. We conclude that tumor cell migration on LM-511 requires that Lu/B-CAM
      competitively modulates cell attachment through integrins. We suggest that this
      competitive interaction is involved in a balance between static and migratory
      cell behaviors. 

PMID- 24036116
TI  - Quantification of interaction strengths between chaperones and tetratricopeptide
      repeat domain-containing membrane proteins.
AB  - The three tetratricopeptide repeat domain-containing docking proteins Toc64,
      OM64, and AtTPR7 reside in the chloroplast, mitochondrion, and endoplasmic
      reticulum of Arabidopsis thaliana, respectively. They are suggested to act during
      post-translational protein import by association with chaperone-bound preprotein
      complexes. Here, we performed a detailed biochemical, biophysical, and
      computational analysis of the interaction between Toc64, OM64, and AtTPR7 and the
      five cytosolic chaperones HSP70.1, HSP90.1, HSP90.2, HSP90.3, and HSP90.4. We
      used surface plasmon resonance spectroscopy in combination with Interaction
      Map(r) analysis to distinguish between chaperone oligomerization and docking
      protein-chaperone interactions and to calculate binding affinities for all tested
      interactions. Complementary to this, we applied pulldown assays as well as
      microscale thermophoresis as surface immobilization independent techniques. The
      data revealed that OM64 prefers HSP70 over HSP90, whereas Toc64 binds all
      chaperones with comparable affinities. We could further show that AtTPR7 is able
      to bind HSP90 in addition to HSP70. Moreover, differences between the HSP90
      isoforms were detected and revealed a weaker binding for HSP90.1 to AtTPR7 and
      OM64, showing that slight differences in the amino acid composition or structure
      of the chaperones influence binding to the tetratricopeptide repeat domain. The
      combinatory approach of several methods provided a powerful toolkit to determine
      binding affinities of similar interaction partners in a highly quantitative
      manner. 

PMID- 24036117
TI  - Mitochondrial ribosomal RNA (rRNA) methyltransferase family members are
      positioned to modify nascent rRNA in foci near the mitochondrial DNA nucleoid.
AB  - We have identified RNMTL1, MRM1, and MRM2 (FtsJ2) as members of the RNA
      methyltransferase family that may be responsible for the three known 2'-O-ribose
      modifications of the 16 S rRNA core of the large mitochondrial ribosome subunit.
      These proteins are confined to foci located in the vicinity of mtDNA nucleoids.
      They show distinct patterns of association with mtDNA nucleoids and/or
      mitochondrial ribosomes in cell fractionation studies. We focused on the role of
      the least studied protein in this set, RNMTL1, to show that this protein
      interacts with the large ribosomal subunit as well as with a series of non
      ribosomal proteins that may be involved in coupling of the rate of rRNA
      transcription and ribosome assembly in mitochondria. siRNA-directed silencing of
      RNMTL1 resulted in a significant inhibition of translation on mitochondrial
      ribosomes. Our results are consistent with a role for RNMTL1 in methylation of
      G(1370) of human 16 S rRNA. 

PMID- 24036118
TI  - Unusual spectral properties of bacteriophytochrome Agp2 result from a
      deprotonation of the chromophore in the red-absorbing form Pr.
AB  - Phytochromes are widely distributed photoreceptors with a bilin chromophore that
      undergo a typical reversible photoconversion between the two spectrally different
      forms, Pr and Pfr. The phytochrome Agp2 from Agrobacterium tumefaciens belongs to
      the group of bathy phytochromes that have a Pfr ground state as a result of the
      Pr to Pfr dark conversion. Agp2 has untypical spectral properties in the Pr form
      reminiscent of a deprotonated chromophore as confirmed by resonance Raman
      spectroscopy. UV/visible absorption spectroscopy showed that the pKa is >11 in
      the Pfr form and ~7.6 in the Pr form. Unlike other phytochromes, photoconversion
      thus results in a pKa shift of more than 3 units. The Pr/Pfr ratio after
      saturating irradiation with monochromatic light is strongly pH-dependent. This is
      partially due to a back-reaction of the deprotonated Pr chromophore at pH 9 after
      photoexcitation as found by flash photolysis. The chromophore protonation and
      dark conversion were affected by domain swapping and site-directed mutagenesis. A
      replacement of the PAS or GAF domain by the respective domain of the prototypical
      phytochrome Agp1 resulted in a protonated Pr chromophore; the GAF domain
      replacement afforded an inversion of the dark conversion. A reversion was also
      obtained with the triple mutant N12S/Q190L/H248Q, whereas each single point
      mutant is characterized by decelerated Pr to Pfr dark conversion. 

PMID- 24036120
TI  - Emotional intelligence, emotions, and feelings of support staff working with
      clients with intellectual disabilities and challenging behavior: an exploratory
      study.
AB  - Working with clients who show challenging behavior can be emotionally demanding
      and stressful for support staff, because this behavior may cause a range of
      negative emotional reactions and feelings. These reactions are of negative
      influence on staff wellbeing and behavior. Research has focused on negative
      emotions of staff. However, a distinction between emotions and feelings has never
      been made in the research field of intellectual disabilities. Negative emotions
      and feelings may be regulated by emotional intelligence, a psychological
      construct that takes into account personal style and individual differences. The
      purpose of this study was to explore the relationship between emotional
      intelligence on the one hand and emotions and feelings on the other. Participants
      were 207 support staff serving clients with moderate to borderline intellectual
      disabilities and challenging behavior. Emotional intelligence, emotions, and
      feelings were measured with questionnaires. The results show that emotional
      intelligence, emotions, and feelings are related. However, found relationships
      were weak. Most significant relations were found between feelings and stress
      management and adaptation elements of emotional intelligence. Because the
      explored variables can change over time they call for a longitudinal research
      approach. 

PMID- 24036119
TI  - Role of the two structural domains from the periplasmic Escherichia coli
      histidine-binding protein HisJ.
AB  - Escherichia coli HisJ is a type II periplasmic binding protein that functions to
      reversibly capture histidine and transfer it to its cognate inner membrane ABC
      permease. Here, we used NMR spectroscopy to determine the structure of apo-HisJ
      (26.5 kDa) in solution. HisJ is a bilobal protein in which domain 1 (D1) is made
      up of two noncontiguous subdomains, and domain 2 (D2) is expressed as the inner
      domain. To better understand the roles of D1 and D2, we have isolated and
      characterized each domain separately. Structurally, D1 closely resembles its
      homologous domain in apo- and holo-HisJ, whereas D2 is more similar to the holo
      form. NMR relaxation experiments reveal that HisJ becomes more ordered upon
      ligand binding, whereas isolated D2 experiences a significant reduction in slower
      (millisecond to microsecond) motions compared with the homologous domain in apo
      HisJ. NMR titrations reveal that D1 is able to bind histidine in a similar manner
      as full-length HisJ, albeit with lower affinity. Unexpectedly, isolated D1 and D2
      do not interact with each other in the presence or absence of histidine, which
      indicates the importance of intact interdomain-connecting elements (i.e. hinge
      regions) for HisJ functioning. Our results shed light on the binding mechanism of
      type II periplasmic binding proteins where ligand is initially bound by D1, and
      D2 plays a supporting role in this dynamic process. 

PMID- 24036121
TI  - Estimating the level of functional ability of children identified as likely to
      have an intellectual disability.
AB  - Screening tools can provide an indication of whether a child may have an
      intellectual disability (ID). Item response theory (IRT) analyses can be used to
      assess whether the statistical properties of the tools are such that their
      utility extends beyond their use as a screen for ID. We used non-parametric IRT
      scaling analyses to investigate whether the Child and Adolescent Intellectual
      Disability Screening Questionnaire (CAIDS-Q) possessed the statistical properties
      that would suggest its use could be extended to estimate levels of functional
      ability and to estimate which (if any) features associated with intellectual
      impairment are consistently indicative of lower or higher levels of functional
      ability. The validity of the two proposed applications was assessed by evaluating
      whether the CAIDS-Q conformed to the properties of the Monotone Homogeneity Model
      (MHM), characterised by uni-dimensionality, local independence and latent
      monotonicity and the Double Monotone Model (DMM), characterised by the
      assumptions of the MHM and, in addition, of non-intersecting item response
      functions. We analysed these models using CAIDS-Q data from 319 people referred
      to child clinical services. Of these, 148 had a diagnosis of ID. The CAIDS-Q was
      found to conform to the properties of the MHM but not the DMM. In practice, this
      means that the CAIDS-Q total scores can be used to quickly estimate the level of
      a person's functional ability. However, items of the CAIDS-Q did not show
      invariant item ordering, precluding the use of individual items in isolation as
      accurate indices of a person's level of functional ability. 

PMID- 24036123
TI  - Structural, catalytic and stabilizing consequences of aromatic cluster variants
      in human carbonic anhydrase II.
AB  - The presence of aromatic clusters has been found to be an integral feature of
      many proteins isolated from thermophilic microorganisms. Residues found in
      aromatic cluster interact via pi-pi or C-H?pi bonds between the phenyl rings,
      which are among the weakest interactions involved in protein stability. The lone
      aromatic cluster in human carbonic anhydrase II (HCA II) is centered on F226 with
      the surrounding aromatics F66, F95 and W97 located 12 A posterior the active
      site; a location which could facilitate proper protein folding and active site
      construction. The role of F226 in the structure, catalytic activity and
      thermostability of HCA II was investigated via site-directed mutagenesis of three
      variants (F226I/L/W) into this position. The measured catalytic rates of the F226
      variants via (18)O-mass spectrometry were identical to the native enzyme, but
      differential scanning calorimetry studies revealed a 3-4 K decrease in their
      denaturing temperature. X-ray crystallographic analysis suggests that the
      structural basis of this destabilization is via disruption and/or removal of weak
      C-H?pi interactions between F226 to F66, F95 and W97. This study emphasizes the
      importance of the delicate arrangement of these weak interactions among aromatic
      clusters in overall protein stability.

PMID- 24036124
TI  - Autologous and acrylic cranioplasty: a review of 10 years and 258 cases.
AB  - INTRODUCTION: Cranioplasty is a well-accepted neurosurgical procedure that has
      application to a wide range of pathologies. Given the varied need for both
      autologous and synthetic cranial grafts, it is important to establish rates of
      procedural complication. METHODS: A retrospective review identified 282 patients
      undergoing cranioplasty at our institution over a 10-year period, of which 249
      patients underwent 258 cranioplasties with either autologous or acrylic flaps. A
      database including patient age, gender, presenting diagnosis, hospital of
      surgery, presence of a drain, and surgical complications was created in order to
      analyze the autologous and acrylic cranioplasty data. RESULTS: A total of 28
      complications were noted, yielding a rate of 10.9% (28/258). There was no
      statistically significant difference in infection rate between autologous and
      acrylic cranioplasty (7.2% vs. 5.8%, P=0.80). Male patients (P=0.007), tumor
      patients (P=0.02), and patients undergoing surgery at the county hospital
      (P=0.06) sustained a statistically higher rate of infection. Among traumatic
      brain injury patients, complex injuries and surgical involvement of the frontal
      sinus carried a significantly higher infection rate of 17% and 38.5%,
      respectively (P=0.03, P=0.001). Postoperative epidural hematoma requiring
      reoperation occurred in 3.5% (9/258) with no difference in hematoma rate with
      placement of a drain (P=1). CONCLUSIONS: Cranioplasty carries a significant risk
      of infection and postoperative hematoma. In this large series comparing
      autologous and acrylic flaps, male patients, tumor patients, and those undergoing
      surgery at the county hospital were at increased risk of postoperative infection.
      Among traumatic brain injury cases, complex injuries and cases with surgical
      involvement of the frontal sinus may portend a higher risk.

PMID- 24036125
TI  - Marine algal fucoxanthin inhibits the metastatic potential of cancer cells.
AB  - Metastasis is major cause of malignant cancer-associated mortality. Fucoxanthin
      has effect on various pharmacological activities including anti-cancer activity.
      However, the inhibitory effect of fucoxanthin on cancer metastasis remains
      unclear. Here, we show that fucoxanthin isolated from brown alga Saccharina
      japonica has anti-metastatic activity. To check anti-metastatic properties of
      fucoxanthin, in vitro models including assays for invasion, migration, actin
      fiber organization and cancer cell-endothelial cell interaction were used.
      Fucoxanthin inhibited the expression and secretion of MMP-9 which plays a
      critical role in tumor invasion and migration, and also suppressed invasion of
      highly metastatic B16-F10 melanoma cells as evidenced by transwell invasion
      assay. In addition, fucoxanthin diminished the expressions of the cell surface
      glycoprotein CD44 and CXC chemokine receptor-4 (CXCR4) which play roles in
      migration, invasion and cancer-endothelial cell adhesion. Fucoxanthin markedly
      suppressed cell migration in wound healing assay and inhibited actin fiber
      formation. The adhesion of B16-F10 melanoma cells to the endothelial cells was
      significantly inhibited by fucoxanthin. Moreover, in experimental lung metastasis
      in vivo assay, fucoxanthin resulted in significant reduction of tumor nodules.
      Taken together, we demonstrate, for the first time, that fucoxanthin suppresses
      metastasis of highly metastatic B16-F10 melanoma cells in vitro and in vivo.

PMID- 24036122
TI  - Nickel-dependent metalloenzymes.
AB  - This review describes the functions, structures, and mechanisms of nine nickel
      containing enzymes: glyoxalase I, acireductone dioxygenase, urease, superoxide
      dismutase, [NiFe]-hydrogenase, carbon monoxide dehydrogenase, acetyl-coenzyme A
      synthase/decarbonylase, methyl-coenzyme M reductase, and lactate racemase. These
      enzymes catalyze their various chemistries by using metallocenters of diverse
      structures, including mononuclear nickel, dinuclear nickel, nickel-iron
      heterodinuclear sites, more complex nickel-containing clusters, and nickel
      tetrapyrroles. Selected other enzymes are active with nickel, but the
      physiological relevance of this metal specificity is unclear. Additional nickel
      containing proteins of undefined function have been identified. 

PMID- 24036126
TI  - LOX-1 deletion and macrophage trafficking in atherosclerosis.
AB  - BACKGROUND: Atherosclerosis is associated with macrophage accumulation. LOX-1 has
      been shown to induce macrophage attachment, and its deletion (LOX-1 knockout, KO)
      reduces atherosclerosis in LDLr KO mice fed a high cholesterol diet. We examined
      differences in macrophage trafficking in age-matched wild type, LOX-1 KO, LDLr
      KO, and LDLr/LOX-1 double KO mice. METHODS: Sections of aortas of mice fed high
      cholesterol diet were collected at weeks 0, 4, 8, 12 and 19 and analyzed by
      immunohistochemistry and flow cytometry. RESULTS: In the LDLr KO mice aorta, CD68
      positivity (macrophage accumulation) increased over time up to 12 weeks, and then
      the accumulation fell modestly but significantly. The periaortal fat and
      adventitia showed more CD68 positivity than the media and intima. This pattern
      was also evident in the non-atherosclerotic areas. Importantly, LOX-1 KO and LDLr
      LOX-1 double KO mice showed diminished CD68 positivity in comparison to wild type
      and LDLR KO mice, respectively. Further, macrophages from LOX-1 KO mice revealed
      a marked reduction in migration (vs. macrophages from wild type mice) in in vitro
      migration assay. CONCLUSIONS: LOX-1 deletion translates into reduction in
      macrophage trafficking in the aorta of LDLr KO mice. Most of the macrophage
      trafficking appears in the subadventitial regions.

PMID- 24036127
TI  - PIAS1 negatively modulates virus triggered type I IFN signaling by blocking the
      DNA binding activity of IRF3.
AB  - During viral infection, production of proinflammatory cytokines including type I
      interferons (IFNs) is under stringent control to avoid detrimental overreaction.
      The protein inhibitor of activated STAT (PIAS) family proteins have been
      recognized as anti-inflammatory molecules by restraining type I IFN induced
      amplifying signaling. Here we identified PIAS1 as an important negative regulator
      of virus-triggered type I IFN signaling. Overexpression of PIAS1 repressed virus
      or RIG-I like receptor stimulated type I IFN transcription, whereas knockdown of
      PIAS1 expression augmented virus-induced production of type I IFNs. PIAS1 with a
      mutation in the SAP domain retained the inhibitory function in virus-induced IFN
      transcription, but abolished the inhibition in IFN-stimulated signaling. SUMO E3
      ligase activity dead mutant PIAS1/C350S still had the comparable inhibitory
      function with WT PIAS1. Further study indicated that PIAS1 interacted with IRF3
      and inhibited the DNA binding activity of IRF3. The C-terminal region of PIAS1
      around a cluster of acidic amino acids is critical for the interaction with IRF3
      and the inhibitory functions of PIAS1. Therefore, these results unveil PIAS1
      functions both at the virus-induced early signaling stage and IFN stimulated
      amplifying stage with distinct mechanisms. PIAS1 is important in maintaining
      proper amounts of type I IFNs and restrains its magnitude when the antiviral
      response intensifies. 

PMID- 24036128
TI  - A peptide targeted against phosphoprotein and leader RNA interaction inhibits
      growth of Chandipura virus -- an emerging rhabdovirus.
AB  - The fatal illness caused by Chandipura virus (CHPV), an emerging pathogen,
      presently lacks any therapeutic option. Previous research suggested that
      interaction between the virally encoded phosphoprotein (P) and the positive sense
      leader RNA (le-RNA) may play an important role in the viral lifecycle. In this
      report, we have identified a beta-sheet/loop motif in the C-terminal domain of
      the CHPV P protein as essential for this interaction. A synthetic peptide
      encompassing this motif and spanning a continuous stretch of 36 amino acids
      (Pep208-243) was found to bind the le-RNA in vitro and inhibit CHPV growth in
      infected cells. Furthermore, a stretch of three amino acid residues at position
      217-219 was identified as essential for this interaction, both in vitro and in
      infected cells. siRNA knockdown-rescue experiments demonstrated that these three
      amino acid residues are crucial for the leader RNA binding function of P protein
      in the CHPV life cycle. Mutations of these three amino acid residues render the
      peptide completely ineffective against CHPV. Effect of inhibition of
      phosphoprotein-leader RNA interaction on viral replication was assayed. Peptide
      Pep208-243 tagged with a cell penetrating peptide was found to inhibit CHPV
      replication as ascertained by real time RT-PCR. The specific inhibition of viral
      growth observed using this peptide suggests a new possibility for designing of
      anti-viral agents against Mononegavirale group of human viruses. 

PMID- 24036129
TI  - Functional connectivity abnormalities vary by amygdala subdivision and are
      associated with psychiatric symptoms in unilateral temporal epilepsy.
AB  - The amygdala has been described as a structure affected by mesial temporal lobe
      epilepsy (MTLE). Indeed, it is suggested that amygdala abnormalities are related
      to the co-morbid depression and anxiety reported in MTLE. In this context, we
      investigated the relation between functional connectivity (FC) emerging from this
      structure in fMRI and depression and anxiety levels reported in MTLE patients. We
      focused on resting-state BOLD activity and evaluated whether FC differences
      emerge from each of three amygdala subdivisions (laterobasal, centromedial and
      superficial) in left and right MTLE groups, compared with healthy controls.
      Results revealed significant differences between patient groups and controls.
      Specifically, the left MTLE group showed abnormal FC for the left-sided seeds
      only. Furthermore, regardless of the seed, we observed more reliable differences
      between the right MTLE group and controls. Further analysis of these results
      revealed correlations between these impaired connectivities and psychiatric
      symptoms in both MTLE groups. Opposite relations, however, were highlighted: the
      more depressed or anxious the right MTLE patients, the closer their FC values
      approached controls; whereas the less anxious the left MTLE patients, the closer
      their FC values were normative. These results highlight how MTLE alter FC
      emerging from the limbic system. Overall, our data demonstrate that right TLE has
      a more maladaptive impact on emotion-related networks, in ways specific to the
      amygdala region, and the emotion symptom involved, than left TLE. 

PMID- 24036130
TI  - Investigation of musicality in birdsong.
AB  - Songbirds spend much of their time learning, producing, and listening to complex
      vocal sequences we call songs. Songs are learned via cultural transmission, and
      singing, usually by males, has a strong impact on the behavioral state of the
      listeners, often promoting affiliation, pair bonding, or aggression. What is it
      in the acoustic structure of birdsong that makes it such a potent stimulus? We
      suggest that birdsong potency might be driven by principles similar to those that
      make music so effective in inducing emotional responses in humans: a combination
      of rhythms and pitches-and the transitions between acoustic states-affecting
      emotions through creating expectations, anticipations, tension, tension release,
      or surprise. Here we propose a framework for investigating how birdsong, like
      human music, employs the above "musical" features to affect the emotions of avian
      listeners. First we analyze songs of thrush nightingales (Luscinia luscinia) by
      examining their trajectories in terms of transitions in rhythm and pitch. These
      transitions show gradual escalations and graceful modifications, which are
      comparable to some aspects of human musicality. We then explore the feasibility
      of stripping such putative musical features from the songs and testing how this
      might affect patterns of auditory responses, focusing on fMRI data in songbirds
      that demonstrate the feasibility of such approaches. Finally, we explore ideas
      for investigating whether musical features of birdsong activate avian brains and
      affect avian behavior in manners comparable to music's effects on humans. In
      conclusion, we suggest that birdsong research would benefit from current advances
      in music theory by attempting to identify structures that are designed to elicit
      listeners' emotions and then testing for such effects experimentally. Birdsong
      research that takes into account the striking complexity of song structure in
      light of its more immediate function - to affect behavioral state in listeners -
      could provide a useful animal model for studying basic principles of music
      neuroscience in a system that is very accessible for investigation, and where
      developmental auditory and social experience can be tightly controlled.

PMID- 24036132
TI  - Glucocorticoid receptor-mediated apoptosis in small-cell lung cancer requires
      interaction with BCL2.
AB  - Small-cell lung cancer (SCLC) tumours are highly aggressive. At the time of
      diagnosis, patients have often developed metastases, and overall prognosis is
      particularly poor, making effective treatment difficult. Novel mechanisms need to
      be identified as treatment targets. We have previously found low levels of the
      glucocorticoid receptor (GR) in SCLC cell lines and demonstrated that over
      expression of GR increases tumour cell death both in vitro and in vivo. We
      hypothesise that low levels of GR impair its inhibitory effect on BCL2 and thus
      provide a survival advantage to SCLC cell lines. The mechanism behind GR-induced
      apoptosis is currently unknown; therefore, pro- and anti-apoptotic genes were
      investigated for their role in GR-mediated apoptosis signalling. We found that
      over-expression of wtGR via retroviral transduction causes the DMS 79 SCLC cell
      line to undergo caspase-mediated apoptosis within 72  h. Neither BAD nor BCL2L11
      (BIM) mRNA and protein levels were affected by GR restoration implying that GR
      does not trigger apoptosis in the SCLC cell lines by up-regulating these pro
      apoptotic genes. The anti-apoptotic BCL2 gene was significantly overexpressed in
      six SCLC cell lines and the BCL2 inhibitor ABT-737 increased apoptosis in all
      three cell lines tested. GR interacted with BCL2 in DMS 153, DMS 79 and COR-L42
      cell lines, suggesting that a protein interaction between GR and BCL2 could play
      a role in GR-induced apoptosis. A deeper understanding of the molecular mechanism
      for increasing GR expression in SCLC could provide novel treatment strategies in
      the future.

PMID- 24036131
TI  - Metastatic mechanisms in follicular cell-derived thyroid cancer.
AB  - Thyroid cancer incidence is rising annually largely related to enhanced detection
      and early stage well-differentiated primary tumors. The prognosis for patients
      with early stage thyroid cancer is outstanding with most patients being cured
      with surgery. In selected cases, I-131 is administered to treat known or
      suspected residual or metastatic disease. Even patients with loco-regional
      metastases typically have an outstanding long-term prognosis, albeit with
      monitoring and occasional intervention for residual or recurrent disease. By
      contrast, individuals with distant metastases from thyroid cancer, particularly
      older patients with larger metastatic burdens and those with poorly
      differentiated tumors, have a poor prognosis. Patients with metastatic anaplastic
      thyroid cancer have a particularly poor prognosis. Published clinical trials
      indicate that transient disease control and partial remissions can be achieved
      with kinase inhibitor therapy directed toward angiogenic targets and that in some
      cases I-131 uptake can be enhanced. However, the direct targets of activity in
      metastatic lesions are incompletely defined and clear evidence that these
      treatments increase the duration or quality of life of patients is lacking,
      underscoring the need for improved knowledge regarding the metastatic process to
      inform the development of new therapies. In this review, we will focus on current
      data and hypotheses regarding key regulators of metastatic dormancy, metastatic
      progression, and the role of putative cancer stem cells.

PMID- 24036133
TI  - Safety and efficacy of everolimus in gastrointestinal and pancreatic
      neuroendocrine tumors after (177)Lu-octreotate.
AB  - Although (177)Lu-octreotate is an effective treatment for patients with
      gastroenteropancreatic neuroendocrine tumors (GEP-NETs), some patients will fail
      or develop disease progression necessitating further treatment. We examined
      whether the safety and efficacy of everolimus after prior treatment with (177)Lu
      octreotate is different from the published safety profile of everolimus in GEP
      NETs. In this multicenter study, 24 GEP-NET patients were included. Adverse
      events were assessed according to the National Cancer Institute Common
      Terminology Criteria for Adverse Events (CTCAE), version 3.0. Tumor response was
      measured according to the Response Evaluation Criteria in Solid Tumors (RECIST),
      version 1.0. Major clinical adverse events (grade 3 or 4) during treatment with
      everolimus were hyperglycemia (20.8%), fatigue (8.3%), thrombocytopenia (8.3%),
      and elevated alanine transaminase levels (8.3%). By radiological review, there
      were four partial responses (16.7%), five patients (62.5%) with stable disease,
      and three patients (12.5%) with progressive disease. For two patients (8.3%), no
      data on tumor response were available. Median progression-free survival (PFS) was
      13.1 months (95% CI, 11.5-21.2). Median PFS of the current study was longer when
      compared with the RADIANT-3 trial (13.1 vs 11.4 months) and shorter when compared
      with the RADIANT-1 trial (13.1 vs 16.7 months). In conclusion, the safety profile
      of everolimus is not influenced by previous treatment with peptide receptor
      radiotherapy.

PMID- 24036134
TI  - Contrast-enhanced MRI-derived scar patterns and associated ventricular
      tachycardias in nonischemic cardiomyopathy: implications for the ablation
      strategy.
AB  - BACKGROUND: There are limited data on typical arrhythmogenic substrates and
      associated ventricular tachycardias (VT) in patients with nonischemic
      cardiomyopathy. The substrate location may have implications for the ablation
      strategy. METHODS AND RESULTS: Nineteen consecutive patients with nonischemic
      cardiomyopathy (age 58+/-14 years, 79% men, left ventricular ejection fraction
      41+/-11%) who underwent contrast-enhanced MRI and VT ablation were included. On
      the basis of 3-dimensional contrast-enhanced MRI-derived scar reconstructions, 8
      patients (42%) had predominant basal anteroseptal scar, 9 patients (47%) had
      predominant inferolateral scar, and 2 patients (11%) had other scar types. Three
      distinct VT morphologies (>=1 of 3 inducible in 16/19 patients) were associated
      with underlying scar type. In 9 patients with anteroseptal scar-related VT (8/9
      predominant scar, 1/9 nonpredominant), ablation target sites (defined as sites
      with >=11/12 pacemap, concealed entrainment or VT termination during ablation)
      were located in the aortic root and/or anteroseptal left ventricular endocardium
      in 8 patients (89%) and in the anterior cardiac vein in 1 patient (11%), with
      additional target sites at the right ventricular septum in 2 patients (22%) and
      at the epicardium in 1 patient (11%). In contrast, in 8 patients with predominant
      inferolateral scar-related VT, target sites were located at the epicardium in 5
      patients (63%) and in the endocardial inferolateral left ventricle in 3 patients
      (37%). CONCLUSIONS: Two typical scar patterns (anteroseptal and inferolateral)
      account for 89% of arrhythmogenic substrates in patients with nonischemic
      cardiomyopathy. Three distinct VT morphologies are highly suggestive of the
      presence of these scars. Anteroseptal scars were, in general, most effectively
      approached from the aortic root or anteroseptal left ventricular endocardium,
      whereas inferolateral scars frequently required an epicardial approach.

PMID- 24036136
TI  - Towards catalyst compartimentation in combined chemo- and biocatalytic processes:
      immobilization of alcohol dehydrogenases for the diastereoselective reduction of
      a beta-hydroxy ketone obtained from an organocatalytic aldol reaction.
AB  - The alcohol dehydrogenases (ADHs) from Lactobacillus kefir and Rhodococcus sp.,
      which earlier turned out to be suitable for a chemoenzymatic one-pot synthesis
      with organocatalysts, were immobilized with their cofactors on a commercially
      available superabsorber based on a literature known protocol. The use of the
      immobilized ADH from L. kefir in the reduction of acetophenone as a model
      substrate led to high conversion (>95%) in the first reaction cycle, followed by
      a slight decrease of conversion in the second reaction cycle. A comparable result
      was obtained when no cofactor was added although a water rich reaction media was
      used. The immobilized ADHs also turned out to be suitable catalysts for the
      diastereoselective reduction of an organocatalytically prepared enantiomerically
      enriched aldol adduct, leading to high conversion, diastereomeric ratio and
      enantioselectivity for the resulting 1,3-diols. However, at a lower catalyst and
      cofactor amount being still sufficient for biotransformations with "free" enzymes
      the immobilized ADH only showed high conversion and >99% ee for the first
      reaction cycle whereas a strong decrease of conversion was observed already in
      the second reaction cycle, thus indicating a significant leaching effect of
      catalyst and/or cofactor. 

PMID- 24036135
TI  - Parcellation of the thalamus into distinct nuclei reflects EphA expression and
      function.
AB  - Intercellular signaling via the Eph receptor tyrosine kinases and their ligands,
      the ephrins, acts to shape many regions of the developing brain. One intriguing
      consequence of Eph signaling is the control of mixing between discrete cell
      populations in the developing hindbrain, contributing to the formation of
      segregated rhombomeres. Since the thalamus is also a parcellated structure
      comprised of discrete nuclei, might Eph signaling play a parallel role in cell
      segregation in this brain structure? Analyses of expression reveal that several
      Eph family members are expressed in the forming thalamus and that cells
      expressing particular receptors form cellular groupings as development proceeds.
      Specifically, expression of receptors EphA4 or EphA7 and ligand ephrin-A5 is
      localized to distinct thalamic domains. EphA4 and EphA7 are often coexpressed in
      regions of the forming thalamus, with each receptor marking discrete thalamic
      domains. In contrast, ephrin-A5 is expressed by a limited group of thalamic
      cells. Within the ventral thalamus, EphA4 is present broadly, occasionally
      overlapping with ephrin-A5 expression. EphA7 is more restricted in its expression
      and is largely nonoverlapping with ephrin-A5. In mutant mice lacking one or both
      receptors or ephrin-A5, the appearance of the venteroposterolateral (VPL) and
      venteroposteromedial (VPM) nuclear complex is altered compared to wild type mice.
      These in vivo results support a role for Eph family members in the definition of
      the thalamic nuclei. In parallel, in vitro analysis reveals a hierarchy of mixing
      among cells expressing ephrin-A5 with cells expressing EphA4 alone, EphA4 and
      EphA7 together, or EphA7 alone. Together, these data support a model in which
      EphA molecules promote the parcellation of discrete thalamic nuclei by limiting
      the extent of cell mixing. 

PMID- 24036137
TI  - Immunogenicity of oral vaccination with Lactococcus lactis derived vaccine
      candidate antigen (UreB) of Helicobacter pylori fused with the human interleukin
      2 as adjuvant.
AB  - Helicobacter pylori (H. pylori) infection remains a significant global public
      health problem. Vaccine, especially edible vaccine, is considered to be effective
      in the management of H. pylori infections. By using recombinant technology,
      Lactococcus lactis (L. lactis) could serve as an antigen-delivering vehicle for
      the development of edible vaccine. The aim of this study was to produce edible
      UreB (urease B) vaccine derived from L. lactis against H. pylori. The UreB
      subunit is the most effective and common immunogen of all strains of H. pylori.
      The UreB was produced as a chimeric protein fused with IL-2 (human interleukin 2)
      as the mucosal adjuvant. Mucosal immunization of mice with recombinant L. lactis
      NZ9000 containing the UreB-IL-2 protein elicited more anti-UreB antibody that
      specifically bounded to the purified bacterial UreB protein and more cytokines
      such as IFN-gamma, IL-4, and IL-17, and had a lower H. pylori burden and urease
      activity than control mice. These results suggest that the recombinant L. lactis
      expressing UreB-IL-2 can be potentially used as an edible vaccine for controlling
      H. pylori infection.

PMID- 24036138
TI  - Risk assessment of additives through soft drinks and nectars consumption on
      Portuguese population: a 2010 survey.
AB  - This study investigated whether the Portuguese population is at risk of exceeding
      ADI levels for acesulfame-K, saccharin, aspartame, caffeine, benzoic and sorbic
      acid through an assessment of dietary intake of additives and specific
      consumption of four types of beverages, traditional soft drinks and soft drinks
      based on mineral waters, energetic drinks, and nectars. The highest mean levels
      of additives were found for caffeine in energetic drinks, 293.5mg/L, for
      saccharin in traditional soft drinks, 18.4 mg/L, for acesulfame-K and aspartame
      in nectars, with 88.2 and 97.8 mg/L, respectively, for benzoic acid in
      traditional soft drinks, 125.7 mg/L, and for sorbic acid in soft drinks based on
      mineral water, 166.5 mg/L. Traditional soft drinks presented the highest
      acceptable daily intake percentages (ADIs%) for acesulfame-K, aspartame, benzoic
      and sorbic acid and similar value for saccharin (0.5%) when compared with soft
      drinks based on mineral water, 0.7%, 0.08%, 7.3%, and 1.92% versus 0.2%, 0.053%,
      0.6%, and 0.28%, respectively. However for saccharin the highest percentage of
      ADI was obtained for nectars, 0.9%, in comparison with both types of soft drinks,
      0.5%. Therefore, it is concluded that the Portuguese population is not at risk of
      exceeding the established ADIs for the studied additives.

PMID- 24036139
TI  - A comparison of ELISA and HPLC methods for determination of ochratoxin A in human
      blood serum in the Czech Republic.
AB  - Ochratoxin A (OTA) is one of the most naturally occurring fungal toxins in food.
      It has been detected in high concentrations in serum samples of nephropathic
      patients and can be applied as one of the markers of potential risk of this
      disease. Also, OTA can cause adverse effects on human health such as genotoxicity
      and is anticipated to be a potential human carcinogen. In this study, enzyme
      linked immunosorbent assay (ELISA) and high performance liquid chromatography
      (HPLC) were applied in analysis of 115 blood serum samples of women in the child
      rearing age from the Czech Republic and both methods were compared. The OTA was
      presented in a broad range of concentrations from 0.037 to 1.130 MUg/L. The
      outcome of ELISA and HPLC measurements were well correlated (r=0.907). However,
      it was observed that ELISA tend to result in underestimating the OTA level at the
      low serum concentrations. Both methods had the same limits of quantification of
      0.050 MUg/L under standard operation conditions. When OTA concentration in a
      sample was too low, the sample was redissolved in only 300 MUL of methanol and
      the detection limit for HPLC was lowered to 0.030 MUg OTA/L.

PMID- 24036140
TI  - Methionine concentration in the diet has a tissue-specific effect on chromosomal
      stability in female mice.
AB  - Inadequate nutrient intake can influence the genome. Since methionine is an
      essential amino acid that may influence DNA integrity due to its role in the one
      carbon metabolism pathway, we were interested in whether methionine imbalance can
      lead to genotoxic events. Adult female Swiss mice were fed a control (0.3% dl
      methionine), methionine-supplemented (2.0% DL-methionine) or methionine-deficient
      (0% DL-methionine) diet over a 10-week period. Chromosomal damage was assessed in
      peripheral blood using a micronucleus test, and DNA damage was assessed in the
      liver, heart and peripheral blood tissues using a comet assay. The mRNA
      expression of the mismatch repair genes Mlh1 and Msh2 was analyzed in the liver.
      The frequency of micronucleus in peripheral blood was increased by 122% in the
      methionine-supplemented group (p<0.05). The methionine-supplemented diet did not
      induce DNA damage in the heart and liver tissues, but it increased DNA damage in
      the peripheral blood. The methionine-deficient diet reduced basal DNA damage in
      liver tissue. This reduction was correlated with decreased mRNA expression of
      Msh2. Our results demonstrate that methionine has a tissue-specific effect
      because methionine-supplemented diet induced both chromosomal and DNA damage in
      peripheral blood while the methionine-deficient diet reduced basal DNA damage in
      the liver.

PMID- 24036141
TI  - Chemical composition of total flavonoids from Salvia chinensia Benth and their
      pro-apoptotic effect on hepatocellular carcinoma cells: potential roles of
      suppressing cellular NF-kappaB signaling.
AB  - Salvia chinensia Benth (S. chinensia) is a medical plant that has been
      traditionally applied for centuries in the treatment of malignant diseases
      including hepatocellular carcinoma (HCC). However, the scientific basis
      underlying its anti-HCC activity has not been fully established. In this study,
      the chemical profiles of total flavonoids from S. chinensia (TFSC) were explored.
      Thirteen compounds which constituted the major components of TFSC were separated
      and identified. Flow cytometry analysis and caspase activity assays showed that
      TFSC dose-dependently induced HepG2 and Huh-7 HCC cell apoptosis. TFSC was also
      shown to substantially suppress NF-kappaB activity in HCC cells. Moreover, TFSC
      significantly repressed transplanted murine H22 ascitic hepatic cancer cell
      growth in vivo. Further studies revealed that TFSC induced HCC cell apoptosis and
      inhibited expressional levels of NF-kappaB responsive genes in transplanted tumor
      tissues. In addition, the toxic impact of TFSC on tumor-bearing mice was
      undetectable. These results indicate that TFSC induces HCC cell apoptosis both in
      vitro and in vivo. The suppression of cellular NF-kappaB activity is implicated
      in the TFSC-mediated HCC cell apoptosis. 

PMID- 24036142
TI  - Graptopetalum paraguayense and resveratrol ameliorates carboxymethyllysine (CML)
      induced pancreas dysfunction and hyperglycemia.
AB  - Hyperglycemia is associated with advanced glycation end products (AGEs).
      Recently, AGEs were found to cause pancreatic damage, oxidative stress, and
      hyperglycemia through the AGE receptor. Carboxymethyllysine (CML) is an AGE but
      whether it induces pancreatic dysfunction remains unclear. Graptopetalum
      paraguayense, a vegetable consumed in Taiwan, has been used in folk medicine and
      is an antioxidant that protects against liver damage. We investigated the
      protective properties of G. paraguayense 95% ethanol extracts (GPEs) against CML
      induced pancreatic damage. The results indicated that resveratrol, GPE, and
      gallic acid (the active compound of GPE) increased insulin synthesis via
      upregulation of pancreatic peroxisome proliferator activated-receptor-gamma
      (PPARgamma) and pancreatic-duodenal homeobox-1 (PDX-1) but inhibited the
      expression of CML-mediated CCAAT/enhancer binding protein-beta (C/EBPbeta), a
      negative regulator of insulin production. Moreover, resveratrol and GPE also
      strongly activated nuclear factor-erythroid 2-related factor 2 (Nrf2) to
      attenuate oxidative stress and improve insulin sensitivity in the liver and
      muscle of CML-injected C57BL/6 mice and resulted in reduced blood glucose levels.
      Taken together, these findings suggested that GPE and gallic acid could
      potentially be used as a food supplement to protect against pancreatic damage and
      the development of diabetes. 

PMID- 24036143
TI  - Germ cell mutagenicity of topoisomerase I inhibitor topotecan detected in the
      male mouse-dominant lethal study.
AB  - To investigate the ability of topotecan, a topoisomerase I-targeting anticancer
      drug, to induce dominant lethal mutations in male mouse germ cells, males were
      treated with single doses of 3, 6 and 12 mg/kg topotecan. Each male was mated at
      4-day intervals to virgin females for a total of nine 4-day mating intervals. The
      two highest doses of topotecan are shown to be mutagenic in post-meiotic cells.
      The greatest effect occurred in those cells which were in the early-spermatid
      stage at the time of exposure. Mice treated with 12 mg/kg topotecan showed an
      additional peak of dominant lethal induction in mature sperm during the first 4
      day matings after treatment. The mutagenic effects were directly correlated with
      free radicals accumulation as an obvious increase in the generation reactive
      oxygen species and 8-hydroxydeoxyguanosine was noted in animals treated with 6
      and 12 mg/kg topotecan. Treatment of male mice with N-acetylcysteine, a free
      radical scavenger, significantly protected mice from topotecan-induce dominant
      lethality. Moreover, N-acetylcysteine had no antagonizing effect on topotecan
      induce topoisomerase-I inhibition. Our study provides evidence that topotecan is
      a germ cell mutagen and its effect is more pronounced during the post-meiotic
      stages through a mechanism that may involves increases in DNA oxidative stress.

PMID- 24036144
TI  - Suppression of dimerumic acid on hepatic fibrosis caused from carboxymethyl
      lysine (CML) by attenuating oxidative stress depends on Nrf2 activation in
      hepatic stellate cells (HSCs).
AB  - Hyperglycemia facilitates the formation of advanced glycation end-products (AGEs)
      in type-2 diabetes. Evidence indicates that carboxymethyl-lysine (CML) is highly
      prevalent in diabetes, resulting in hepatic fibrosis. The current study was
      designed to evaluate the effects of dimerumic acid (DMA) identified from Monascus
      fermented products on receptor for AGEs (RAGE) signal and hepatic stellate cells
      (HSCs) activation by CML treatment. We found that DMA (50 MUM) eliminated
      collagen generation, mRNA expressions of alpha-smooth muscle actin (alpha-SMA),
      platelet-derived growth factor-beta receptor (PDGF-betaR), and procollagen 1a1
      (proCol-1a1) in CML (100 MUg/ml)-treated HSCs, and these effects were similar to
      allyl isothiocyanate (AITC; 50 MUM). In addition, the suppression of alpha-SMA,
      PDGF-betaR, proCol-1a1 by DMA were abolished while nuclear factor-erythroid 2
      related factor 2 (Nrf2) silence in CML-treated HSCs. These findings suggested
      that DMA and AITC increased Nrf2 and glutamate-cysteine ligase (GCL) activities
      thereby inhibiting oxidative stress caused by CML and showing anti-fibrogentic
      effect in HSCs.

PMID- 24036145
TI  - Pharmaceuticals and personal care products in the aquatic environment in China: a
      review.
AB  - Pharmaceuticals and personal care products (PPCPs) have been detected as
      contaminants of emerging concern ubiquitously in the aquatic environment in China
      and worldwide. A clear picture of PPCP contamination in the Chinese aquatic
      environment is needed to gain insight for both research and regulatory needs
      (e.g. monitoring, control and management). The occurrence data of 112 PPCPs in
      waters and sediments in China has been reviewed. In most cases, the detected
      concentration of these PPCPs in waters and sediments were at ng/L and ng/g
      levels, which were lower than or comparable to those reported worldwide. A
      screening level risk assessment (SLERA) identified six priority PPCPs in surface
      waters, namely erythromycin, roxithromycin, diclofenac, ibuprofen, salicylic acid
      and sulfamethoxazole. The results of SLERA also revealed that the hot spots for
      PPCP pollution were those river waters affected by the megacities with high
      density of population, such as Beijing, Tianjin, Guangzhou and Shanghai.
      Limitations of current researches and implications for future research in China
      were discussed. Some regulatory issues were also addressed. 

PMID- 24036146
TI  - Mechanical and thermal properties of polypropylene (PP) composites filled with
      modified shell waste.
AB  - Shell waste, with its high content of calcium carbonate (CaCO3) plus organic
      matrix, has a potential to be used as a bio-filler. In this work, shell waste was
      modified by furfural and then incorporated to reinforce polypropylene (PP). The
      shell waste and modified powder were characterized by means of X-ray diffraction
      (XRD), scanning electron microscopy equipped with an energy dispersive
      spectrometer (SEM-EDS), X-ray photoelectronic spectroscopy (XPS), and Fourier
      transformed infrared spectroscopy (FTIR). The mechanical and thermal properties
      of neat PP and PP composites were investigated as well. Thermal gravimetric (TG)
      analyses confirmed the reinforcing role of modified powder in PP composites. The
      mechanical properties studied showed that adding modified powder could
      significantly increase the impact strength, elongation at break point and
      flexural modulus of composites. The maximum incorporation content could reach 15
      wt.% with a good balance between toughness and stiffness of PP composites.
      Differential scanning calorimetry (DSC) results showed that the modified powder
      could act as a nucleating agent and thus increase the crystallization temperature
      of PP. Polarized optical microscopy (POM) observation also indicated that the
      introduction of modified powder could promote the heterogeneous nucleation of PP
      matrix.

PMID- 24036147
TI  - An integrated experimental-modeling approach to study the acid leaching behavior
      of lead from sub-micrometer lead silicate glass particles.
AB  - This work focuses on the development of a procedure to study the mechanism of
      leaching of lead from sub-micrometer lead glass particles using 0.3 mo ll(-1)
      HNO3 as a leachant. Glass particles with an effective size distribution range
      from 0.05 to 1.4 MUm were generated by laser ablation (213 nm Nd:YAG laser) and
      collected on an inline 0.2 MUm syringe filter. Subsequently, the glass particles
      on the filter were subjected to online leaching and continuous monitoring of lead
      (Pb-208) in the leachate by quadrupole ICP-MS. The lead leaching profile, aided
      by the particle size distribution information from cascade impaction, was
      numerically fitted to a mathematical model based on the glass intraparticle
      diffusion, liquid film distribution and thermodynamic glass-leachant distribution
      equilibrium. The findings of the modeling show that the rate-limiting step of
      leaching is the migration of lead from the core to the surface of the glass
      particle by an ion-exchange mechanism, governed by the apparent intraparticle
      lead diffusivity in glass which was calculated to be 3.1 * 10(-18) m(2)s(-1).
      Lead leaching is illustrated in the form of graphs and animations of
      intraparticle lead release (in time and intraparticle position) from particles
      with sizes of 0.1 and 0.3 MUm.

PMID- 24036148
TI  - Lead retention in a calcareous soil influenced by calcium and phosphate
      amendments.
AB  - Phosphate amendments in calcareous lead (Pb)-contaminated soils to immobilize Pb
      may be hindered due to competition of Pb with calcium (Ca) that may inhibit the
      retention of Pb as a precipitation mechanism. This study explored the retention
      of Pb in a calcareous soil spiked and aged with 500 mg kg(-1) Pb(2+) and amended
      with H2PO4(-). In addition, Ca(2+) was added immediately or three days before or
      after phosphate, after which ryegrass (Lolium perenne) was planted. Diethylene
      triamine pentaacetic acid (DTPA)-extractable Pb of the soils in which Ca was
      added immediately after phosphate was lower than those only amended with
      phosphate or when Ca was added three days before or after phosphate. The addition
      of Ca immediately after phosphate resulted in the greatest reduction of ammonia
      acetate-exchangeable Ca concentration, Olsen-P concentration, and carbonate phase
      Pb. Higher plant biomass yields were observed for the simultaneous P and Ca
      treatment. The results of the study demonstrate that co-added Ca and P may help
      reduce Pb availability by forming fresh Ca-P sorbent phases to retain Pb through
      an adsorption-substitution mechanism, which may play an important role in the
      sequestration of Pb in calcareous soils with soluble phosphate in addition to the
      mechanism of the direct precipitation as pyromorphite.

PMID- 24036149
TI  - Synthesis and application of a unified sorbent for simultaneous preconcentration
      and determination of trace metal pollutants in natural waters.
AB  - A flat sheet sorbent with poly(hydroxamic acid) groups anchored on the
      microporous structure of poly(propylene) membrane was developed and applied for
      the preconcentration and determination of heavy elements from natural waters. The
      designing of the sorbent involved UV-irradiation induced graft polymerization of
      acrylamide using N,N'-methylene-bis-acrylamide (MBA) as the crosslinker on the
      poly(propylene) base followed by chemical modification of the grafted membrane to
      generate crosslinked poly(hydroxamic acid) (PHA) groups in its pores. The
      synthesized PHA-membrane was found to preconcentrate U, V, Cu, Cr, Fe and Pb
      quantitatively (95%) from aqueous samples over a wide pH range of 4-9. The sorbed
      trace elements were quantified by direct analysis of the membrane using Energy
      Dispersive X-ray Fluorescence (EDXRF). To test the applicability of the developed
      sorbent to real samples, interference effect of common matrix elements like Na,
      K, Ca and Mg on the uptake of the analytes at sub MUg mL(-1) level was studied.
      The PHA sorbent was found to be immune to interferences from Na, K and Mg up to
      1000 MUg mL(-1) and Ca up to 100 MUg mL(-1) for an analyte concentration of 1 MUg
      mL(-1). The method detection limit for EDXRF measurement was 6-30 ng using a 2 cm
      * 2 cm sorbent.

PMID- 24036150
TI  - Physiological responses of Microcystis aeruginosa under the stress of antialgal
      actinomycetes.
AB  - Eutrophication has occurred frequently in various lakes and reservoirs, and the
      metabolic excretion produced during the algae growth causes serious water
      pollution and threatens ecological security. Biological control approaches such
      as screening bacteria with the capability to degrade cyanobacteria are an
      environment-friendly way. An isolated antialgal strain Streptomyces sp. KY-34,
      was applied to degrade the cyanobacterium Microcystis aeruginosa, and the
      possible biodegradation mechanism was investigated. The results showed that the
      fermentation liquor of Streptomyces sp. KY-34 could inhibit the growth of M.
      aeruginosa by restrained the synthesis of chlorophyll and photosynthetic
      pigments, and decreasing the contents of cellular protein and non-protein,
      accordingly led to the increase of malondialdehyde content, and the activities of
      superoxide dismutase, catalase and peroxidase in algae cells. In addition, the
      variation of the cellular ultrastructure indicated a serious change in algal
      physiology. It's revealed that the biodegradation mechanism of M. aeruginosa
      should primarily be that Streptomyces sp. KY-34 caused the damage of algae cell
      membrane and led to the increases of antioxidant enzymes, and then the growth of
      M. aeruginosawas inhibited. 

PMID- 24036152
TI  - BTNL8, a butyrophilin-like molecule that costimulates the primary immune
      response.
AB  - The role of the B7 family molecules in the regulation of the immune response is
      well documented. A large body of experimental evidence indicates that
      costimulatory molecules such as B7-1, B7-2, B7-DC, B7-H1, B7-H2, B7-H3 and B7-H4
      are critical for initiation, maintenance and down-regulation of the immune
      response. However the immunological function of butyrophilin (BTN)-like
      molecules, which are a part of the expanded B7 family, is not known. Here, we
      demonstrate that the extracellular portion of human BTNL8 can augment Ag-induced
      activation of T lymphocytes. BTNL8 has two alternatively spliced forms: B7-like
      and BTN-like. Both isoforms of BTNL8 were expressed concurrently in various human
      tissues. A putative BTNL8 receptor was detected only on resting T lymphocytes.
      Administration of BTNL8Ig fusion protein into mice promoted production of Ag
      specific IgG during the primary, but not the secondary immune responses. BTNL8
      may therefore play an essential role in priming of naive T lymphocytes. 

PMID- 24036153
TI  - Characterization of the microtubule-binding activity of kinesin-like calmodulin
      binding protein from Dunaliella salina.
AB  - Although the C-terminal motor and the N-terminal myosin-like domains of KCBP in
      Dunaliella salina (DsKCBP) are implicated in interaction with the microtubules,
      its microtubule binding property has not been addressed. It has been shown that
      several calmodulin isoforms suppress the microtubule binding activity of KCBP,
      but whether the calmodulin-like protein (CLP) has this ability remains unknown.
      The results of our previous study showed that there are two microtubule binding
      sites in DsKCBP, motor domain at the C-terminus and MyTH4-FREM at the N-terminus.
      In the present study, MyTH4, without the companion of FERM, was identified as the
      minimal domain responsible for interaction with the microtubules in the N
      terminal of DsKCBP. CLP interacted with the calmodulin-binding domain of DsKCBP
      in the presence of Ca(2+), and inhibited the microtubule-binding activity of
      motor domain but not MyTH4 domain. Furthermore, MyTH4 domain in the N-terminus of
      DsKCBP was responsible for binding to the microtubules, and had 10-fold weaker
      affinity to the microtubules than the motor domain. 

PMID- 24036151
TI  - MIR106B and MIR93 prevent removal of bacteria from epithelial cells by disrupting
      ATG16L1-mediated autophagy.
AB  - BACKGROUND & AIMS: Variants in genes that regulate autophagy have been associated
      with Crohn's disease (CD). Defects in autophagy-mediated removal of pathogenic
      microbes could contribute to the pathogenesis of CD. We investigated the role of
      the microRNAs (miRs) MIR106B and MIR93 in induction of autophagy and bacterial
      clearance in human cell lines and the correlation between MIR106B and autophagy
      related gene 16L1 (ATG16L1) expression in tissues from patients with CD. METHODS:
      We studied the ability of MIR106B and MIR93 to regulate ATG transcripts in human
      cancer cell lines (HCT116, SW480, HeLa, and U2OS) using luciferase report assays
      and bioinformatics analyses; MIR106B and MIR93 mimics and antagonists were
      transfected into cells to modify levels of miRs. Cells were infected with LF82, a
      CD-associated adherent-invasive strain of Escherichia coli, and monitored by
      confocal microscopy and for colony-forming units. Colon tissues from 41 healthy
      subjects (controls), 22 patients with active CD, 16 patients with inactive CD,
      and 7 patients with chronic inflammation were assessed for levels of MIR106B and
      ATG16L1 by in situ hybridization and immunohistochemistry. RESULTS: Silencing
      Dicer1, an essential processor of miRs, increased levels of ATG protein and
      formation of autophagosomes in cells, indicating that miRs regulate autophagy.
      Luciferase reporter assays indicated that MIR106B and MIR93 targeted ATG16L1
      messenger RNA. MIR106B and MIR93 reduced levels of ATG16L1 and autophagy; these
      increased after expression of ectopic ATG16L1. In contrast, MIR106B and MIR93
      antagonists increased formation of autophagosomes. Levels of MIR106B were
      increased in intestinal epithelia from patients with active CD, whereas levels of
      ATG16L1 were reduced compared with controls. Levels of c-Myc were also increased
      in intestinal epithelia of patients with active CD compared with controls. These
      alterations could impair removal of CD-associated bacteria by autophagy.
      CONCLUSIONS: In human cell lines, MIR106B and MIR93 reduce levels of ATG16L1 and
      autophagy and prevent autophagy-dependent eradication of intracellular bacteria.
      This process also appears to be altered in colon tissues from patients with
      active CD.

PMID- 24036154
TI  - RecQ helicase acts before RuvABC, RecG and XerC proteins during recombination in
      recBCD sbcBC mutants of Escherichia coli.
AB  - The RecQ helicase is required by the RecF recombination pathway that is operative
      in recBC(D) sbcB sbcC(D) mutants of Escherichia coli. Genetic data suggest that
      RecQ participates in resection of DNA ends during initiation of recombination. In
      vitro, RecQ can unwind a variety of DNA substrates, including recombination
      intermediates such as D-loops and Holliday junctions. However, its potential role
      in processing of recombination intermediates during the late stage of the RecF
      pathway has not been genetically tested. Here we studied the effect of a recQ
      mutation on transductional recombination and DNA repair after gamma-irradiation
      in DeltarecBCD DeltasbcB sbcC strains deficient for RuvABC, RecG and XerC
      proteins. RuvABC and RecG proteins process recombination intermediates in the
      late stage of recombination, whereas XerC is required to resolve chromosome
      dimers formed upon recombination. Our results do not reveal any substantial
      synergistic effect between the recQ mutation, on one hand, and ruvABC, recG and
      xerC mutations on the other. In addition, the recQ mutation suppresses chromosome
      segregation defects in gamma-irradiated ruvABC recG and xerC mutants. These
      results suggest that RecQ acts upstream of RuvABC, RecG and XerC proteins, a
      finding that is compatible with its primary role in initiation of the RecF
      recombination pathway.

PMID- 24036155
TI  - Engaging patients in medication reconciliation via a patient portal following
      hospital discharge.
AB  - Few ambulatory medication reconciliation tools exist. Transitions between
      inpatient and outpatient care can result in medication discrepancies. An
      interdisciplinary team designed a new 'Secure Messaging for Medication
      Reconciliation Tool' (SMMRT) within a patient web portal and piloted it among 60
      patients at a Veterans Affairs hospital, an integrated system with a shared
      electronic health record. Recently discharged patients used SMMRT to view their
      medications in a secure email message and replied using SMMRT's interactive form,
      verifying their medication regimens and clarifying any inaccuracies. In total,
      108 medication discrepancies and 23 potential adverse drug events (ADEs) were
      seen. Nearly 50% of the potential ADEs were classified as serious. Overall,
      participants were enthusiastic about SMMRT; 90% said they would use SMMRT again.
      Enabling patients to conduct medication reconciliation through a web portal is
      feasible in the transition from inpatient to outpatient care and may improve
      medication safety. 

PMID- 24036156
TI  - An integrative review of information systems and terminologies used in local
      health departments.
AB  - OBJECTIVE: The purpose of this integrative review based on the published
      literature was to identify information systems currently being used by local
      health departments and to determine the extent to which standard terminology was
      used to communicate data, interventions, and outcomes to improve public health
      informatics at the local health department (LHD) level and better inform
      research, policy, and programs. MATERIALS AND METHODS: Whittemore and Knafl's
      integrative review methodology was used. Data were obtained through key word
      searches of three publication databases and reference lists of retrieved articles
      and consulting with experts to identify landmark works. The final sample included
      45 articles analyzed and synthesized using the matrix method. RESULTS: The
      results indicated a wide array of information systems were used by LHDs and
      supported diverse functions aligned with five categories: administration;
      surveillance; health records; registries; and consumer resources. Detail
      regarding specific programs being used, location or extent of use, or
      effectiveness was lacking. The synthesis indicated evidence of growing interest
      in health information exchange groups, yet few studies described use of data
      standards or standard terminology in LHDs. DISCUSSION: Research to address these
      gaps is needed to provide current, meaningful data that inform public health
      informatics research, policy, and initiatives at and across the LHD level.
      CONCLUSIONS: Coordination at a state or national level is recommended to collect
      information efficiently about LHD information systems that will inform
      improvements while minimizing duplication of efforts and financial burden. Until
      this happens, efforts to strengthen LHD information systems and policies may be
      significantly challenged.

PMID- 24036157
TI  - Immunologic consequences of chemotherapy for ovarian cancer: impaired responses
      to the influenza vaccine.
AB  - OBJECTIVES: To examine the effect of chemotherapy for ovarian cancer on
      immunologic function and to define the effect on the serologic response to the
      influenza vaccine. METHODS: Under IRB approved protocols, patients with ovarian
      cancer were administered seasonal trivalent killed influenza vaccines. Peripheral
      blood was collected for immunologic assessments. Serum was analyzed for
      hemagglutination inhibition (HAI) antibody titers. Peripheral blood mononuclear
      cells were isolated to characterize T and B cell populations and function.
      RESULTS: Thirty-one patients were recruited: 13 in remission receiving a
      dendritic cell vaccine with or without a single dose of low-dose
      cyclophosphamide, 3 in remission not receiving treatment, and 15 undergoing
      standard therapy. Significant effects on T cell and B cell subset distributions
      were seen. Functional effects were also seen. Few patients were able to mount a 4
      fold HAI antibody response. A 4-fold response was observed for H1N1 in 20%, for
      H3N2 in 26%, and for influenza B in 6%. Pre-existing exposure to influenza was
      predictive of responders. CONCLUSIONS: Despite CDC recommendations that patients
      undergoing chemotherapy receive influenza vaccine, there is little evidence to
      support its serologic effectiveness in this population. Patients with ovarian
      cancer are almost uniformly unable to mount a meaningful antibody response. These
      findings have serious implications for future resource allocation for both
      seasonal and novel pandemic influenza outbreak and understanding the immunologic
      deficits as a result of chemotherapy may improve patient care.

PMID- 24036159
TI  - Statistical analysis of clinical prediction rules for rehabilitation
      interventions: current state of the literature.
AB  - Deriving clinical prediction rules (CPRs) to identify specific characteristics of
      patients who would likely respond to certain interventions has become a research
      priority in physical rehabilitation. Understanding the appropriate statistical
      principles and methods of analyses underlying the derivation of CPRs is important
      for future rehabilitation research and clinical applications. In this article, we
      aimed to provide an overview of statistical techniques used for the derivation of
      CPRs to predict success following physical therapy interventions and to generate
      recommendations for improvements in CPR derivation research and statistical
      analysis in rehabilitation. We have summarized the current state of CPR
      intervention-related research by reviewing 26 studies. A common technique was
      found in most studies and included univariate association of factors with
      treatment success, stepwise logistic regression to determine the most
      parsimonious set of predictors for success, and calculation of accuracy
      statistics (focusing on positive likelihood ratios). We identified several
      shortcomings related to inadequate ratio of events by number of predictors, lack
      of standardization regarding acceptable interobserver reliability of predictors,
      questionable handling of predictors including reliance on univariate analysis and
      early categorization, and not accounting for dependence and collinearity of
      predictors in multivariable model construction. Interpretation of the derived
      CPRs was found to be difficult due to lack of precision of estimates and
      paradoxical findings when a subset of the predictors yielded a larger positive
      likelihood ratio than did the full set of predictors. Finally, we make
      recommendations regarding how to strengthen the use of statistical principles and
      methods to create consistency across rehabilitation research for CPR derivations.

PMID- 24036158
TI  - Interaction of immunosuppressive drugs with human organic anion transporter (OAT)
      1 and OAT3, and multidrug resistance-associated protein (MRP) 2 and MRP4.
AB  - Renal proximal tubule transporters can play a key role in excretion,
      pharmacokinetic interactions, and toxicity of immunosuppressant drugs.
      Basolateral organic anion transporters (OATs) and apical multidrug resistance
      associated proteins (MRPs) contribute to the active tubular uptake and urinary
      efflux of these drugs, respectively. We studied the interaction of 12
      immunosuppressants with OAT1- and OAT3-mediated [(3)H]-methotrexate (MTX) uptake
      in cells, and adenosine triphosphate-dependent [(3)H]-MTX transport in membrane
      vesicles isolated from human embryonic kidney 293 cells overexpressing human MRP2
      and MRP4. Our results show that at a clinically relevant concentration of 10 MUM,
      mycophenolic acid inhibited both OAT1- and OAT3-mediated [(3)H]-MTX uptake.
      Cytarabine, vinblastine, vincristine, hydrocortisone, and mitoxantrone inhibited
      only OAT1, whereas tacrolimus, azathioprine, dexamethasone, cyclosporine, and 6
      mercaptopurine had no effect on both transporters. Cyclophosphamide stimulated
      OAT1, but did not affect OAT3. With regard to the apical efflux transporters,
      mycophenolic acid, cyclophosphamide, hydrocortisone, and tacrolimus inhibited
      MRP2 and MRP4, whereas mitoxantrone and dexamethasone stimulated [(3)H]-MTX
      transport by both transporters. Cyclosporine, vincristine, and vinblastine
      inhibited MRP2 only, whereas 6-mercaptopurine inhibited MRP4 transport activity
      only. Cytarabine and azathioprine had no effect on either transporter. In
      conclusion, we charted comprehensively the differences in inhibitory action of
      various immunosuppressive agents against the 4 key renal anion transporters, and
      we provide evidence that immunosuppressant drugs can modulate OAT1-, OAT3-, MRP2
      , and MRP4-mediated transport of MTX to different extents. The data provide a
      better understanding of renal mechanisms underlying drug-drug interactions and
      nephrotoxicity concerning combination regimens with these compounds in the
      clinic. 

PMID- 24036160
TI  - Scaling properties of the subjective index of physical and social outcome after
      stroke in a study population unselected by age.
AB  - OBJECTIVE: To investigate the scaling properties of the Subjective Index of
      Physical and Social Outcome (SIPSO) after stroke in survivors to hospital
      discharge, unselected by age. DESIGN: Factor, Mokken, and Rasch analyses of the
      SIPSO using data from a prospective observational cohort study. SETTING: Three
      acute care hospitals. PARTICIPANTS: Consecutive admissions (N=312) with acute
      stroke, unselected by age. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Patient- or proxy-reported SIPSO, collected by postal survey 6 months after
      stroke. RESULTS: Complete SIPSO questionnaires were returned by 166 of 268
      survivors (median age, 72y; interquartile range, 66-81y). Factor and Mokken
      analyses supported both 1- and 2-factor solutions. Fit to the Rasch model for the
      10-item scale was poor (chi(2) test for item-trait interaction, chi(2)=69.6;
      P<.001). Differential item functioning by sex and age was demonstrated for the
      physical subscore and was dealt with through the creation of 2 super items,
      resulting in a good fit to the Rasch model (chi(2)=2.35; P=.67), ordered
      thresholds, good targeting to the latent trait, and reasonable separation
      reliability (Person-Separation Index, 0.8). For the social subscore, no
      differential item functioning was demonstrated by age or sex. Local dependence
      was dealt with through the creation of 2 super items. Thereafter, fit to the
      Rasch model (chi(2)=5.21; P=.27) and targeting to the latent trait were good, and
      thresholds ordered. Separation reliability was poor (Person-Separation Index,
      .67). CONCLUSIONS: The 10-item SIPSO is a valid ordinal scale in a population
      including older stroke survivors. A physical and social subscale structure is
      also supported. Subscales can be manipulated to fit the Rasch model, and a
      conversion table for conversion to an interval scale is provided. The social
      subscore has poor separation reliability, limiting its use in older stroke
      survivors.

PMID- 24036161
TI  - Pain and the risk for falls in community-dwelling older adults: systematic review
      and meta-analysis.
AB  - OBJECTIVE: To conduct a systematic review and meta-analysis to establish the
      association between pain and falls in community-dwelling older adults. DATA
      SOURCES: Electronic databases from inception until March 1, 2013, including
      Cochrane Library, CINAHL, EBSCO, EMBASE, PubMed, and PsycINFO. STUDY SELECTION:
      Two reviewers independently conducted the searches and completed methodological
      assessment of all included studies. Studies were included that (1) focused on
      adults older than 60 years; (2) recorded falls over 6 or more months; and (3)
      identified a group with and without pain. Studies were excluded that included (1)
      participants with dementia or a neurologic condition (eg, stroke); (2)
      participants whose pain was caused by a previous fall; or (3) individuals with
      surgery/fractures in the past 6 months. DATA EXTRACTION: One author extracted all
      data, and this was independently validated by another author. DATA SYNTHESIS: A
      total of 1334 articles were screened, and 21 studies met the eligibility
      criteria. Over 12 months, 50.5% of older adults with pain reported 1 or more
      falls compared with 25.7% of controls (P<.001). A global meta-analysis with 14
      studies (n=17,926) demonstrated that pain was associated with an increased odds
      of falling (odds ratio [OR]=1.56; 95% confidence interval [CI], 1.36-1.79;
      I(2)=53%). A subgroup meta-analysis incorporating studies that monitored falls
      prospectively established that the odds of falling were significantly higher in
      those with pain (n=4674; OR=1.71; 95% CI, 1.48-1.98; I(2)=0%). Foot pain was
      strongly associated with falls (n=691; OR=2.38; 95% CI, 1.62-3.48; I(2)=8%) as
      was chronic pain (n= 5367; OR=1.80; 95% CI, 1.56-2.09; I(2)=0%). CONCLUSIONS:
      Community-dwelling older adults with pain were more likely to have fallen in the
      past 12 months and to fall again in the future. Foot and chronic pain were
      particularly strong risk factors for falls, and clinicians should routinely
      inquire about these when completing falls risk assessments.

PMID- 24036162
TI  - Compound selection for development - is salt formation the ultimate answer?
      Experiences with an extended concept of the "100mg approach".
AB  - In order to select the best candidates for development, physicochemical criteria
      such as solubility, chemical and physical stability, hygroscopicity, and thermal
      characteristics need to be evaluated as early as possible and balanced against
      other important criteria such as pharmacology or pharmacokinetics. It could be
      shown, that our miniaturized pharmaceutical profiling concept ("100mg approach"),
      is capable to reliably identify potential development issues of drug candidates,
      which, therefore, can be approached early on. Salt formation is a well
      established strategy to improve unfavorable properties, in particular poor
      solubility. This article describes our stepwise approach on salt screening,
      including selection criteria, and summarizes the observations we had during
      compound investigation. Considering a data base of 337 compounds (salts and
      uncharged substances), experiences with various counterions evaluated over the
      last 10years are discussed. We realized that salt formation usually improves poor
      solubility of a given candidate, but this is often at the cost of other
      attributes being relevant for pharmaceutical development. Surprisingly, in more
      than 50% of all cases the "free form" was finally selected after carefully
      weighing all compound characteristics. Therefore, we conclude that an early salt
      selection strategy is of utmost importance to predict potential development
      issues and to enable the provision of alternative physical forms. However, salt
      formation itself is not necessarily the best solution to meet all development
      requirements. The selection of a free form (acid or base) in combination with
      advanced formulation strategies should always be considered, sometimes as best
      compromise. 

PMID- 24036163
TI  - Preparation of sustained-release coated particles by novel microencapsulation
      method using three-fluid nozzle spray drying technique.
AB  - We prepared sustained-release microcapsules using a three-fluid nozzle (3N) spray
      drying technique. The 3N has a unique, three-layered concentric structure
      composed of inner and outer liquid nozzles, and an outermost gas nozzle.
      Composite particles were prepared by spraying a drug suspension and an
      ethylcellulose solution via the inner and outer nozzles, respectively, and mixed
      at the nozzle tip (3N-PostMix). 3N-PostMix particles exhibited a corrugated
      surface and similar contact angles as ethylcellulose bulk, thus suggesting
      encapsulation with ethylcellulose, resulting in the achievement of sustained
      release. To investigate the microencapsulation process via this approach and its
      usability, methods through which the suspension and solution were sprayed
      separately via two of the four-fluid nozzle (4N) (4N-PostMix) and a mixture of
      the suspension and solution was sprayed via 3N (3N-PreMix) were used as
      references. It was found that 3N can obtain smaller particles than 4N. The
      results for contact angle and drug release corresponded, thus suggesting that 3N
      PostMix particles are more effectively coated by ethylcellulose, and can achieve
      higher-level controlled release than 4N-PostMix particles, while 3N-PreMix
      particles are not encapsulated with pure ethylcellulose, leading to rapid
      release. This study demonstrated that the 3N spray drying technique is useful as
      a novel microencapsulation method. 

PMID- 24036164
TI  - Impact of process parameters on the breakage kinetics of poorly water-soluble
      drugs during wet stirred media milling: a microhydrodynamic view.
AB  - Wet stirred media milling has proven to be a robust process for producing
      nanoparticle suspensions of poorly water-soluble drugs. As the process is
      expensive and energy-intensive, it is important to study the breakage kinetics,
      which determines the cycle time and production rate for a desired fineness.
      Although the impact of process parameters on the properties of final product
      suspensions has been investigated, scant information is available regarding their
      impact on the breakage kinetics. Here, we elucidate the impact of stirrer speed,
      bead concentration, and drug loading on the breakage kinetics via a
      microhydrodynamic model for the bead-bead collisions. Suspensions of
      griseofulvin, a model poorly water-soluble drug, were prepared in the presence of
      two stabilizers: hydroxypropyl cellulose and sodium dodecyl sulfate. Laser
      diffraction, scanning electron microscopy, and rheometry were used to
      characterize them. Various microhydrodynamic parameters including a newly defined
      milling intensity factor was calculated. An increase in either the stirrer speed
      or the bead concentration led to an increase in the specific energy and the
      milling intensity factor, consequently faster breakage. On the other hand, an
      increase in the drug loading led to a decrease in these parameters and
      consequently slower breakage. While all microhydrodynamic parameters provided
      significant physical insight, only the milling intensity factor was capable of
      explaining the influence of all parameters directly through its strong
      correlation with the process time constant. Besides guiding process optimization,
      the analysis rationalizes the preparation of a single high drug-loaded batch (20%
      or higher) instead of multiple dilute batches. 

PMID- 24036165
TI  - Scutellariae radix suppresses LPS-induced liver endothelial cell activation and
      inhibits hepatic stellate cell migration.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Liver fibrosis is the result of long-term liver
      damage and the wound-healing process, in which the hepatic stellate cell (HSC)
      plays a crucial role during fibrogenesis. The liver sinusoidal endothelial cell
      (LSEC) is a liver-resident scavenger, contributing to sinusoidal remodeling, HSC
      activation and liver fibrosis. Lipopolysaccharide (LPS) causes an inflammatory
      reaction associated with portal circulation and LSECs signaling. Scutellariae
      radix, the root of Scutellaria baicalensis Georgi, is a Chinese herb widely used
      for liver diseases. However, its effect on LSEC activation and HSC migration in
      liver fibrosis has not been investigated yet. AIM OF THIS STUDY: LPS-induced rat
      LSEC (rLSEC) activation was used as a model to screen and explore the active
      components of Scutellariae radix. The anti-fibrotic effect of Scutellariae radix
      on rLSEC activation and rHSC migration was further investigated. MATERIALS AND
      METHODS: LPS-induced rLSEC mRNA expression, including VEGF, VEGFR, MCP-1, and TGF
      beta1, were examined by real-time PCR analyses. MCP-1 protein levels were
      measured by an ELISA kit. rLSEC conditioned medium on rHSC migration was measured
      by wound-healing assay and transwell chemoattraction assay. RESULTS: Results
      showed LPS-induced rLSEC activation with upregulated MCP-1 mRNA and protein
      expressions, and that rLSEC-condition medium enhanced rHSC migration. Both
      baicalein and wogonin from the active subfraction significantly reduced MCP-1
      expression, but only baicalein markedly inhibited rHSC migration in rLSEC
      conditioned medium. CONCLUSION: This study demonstrated that Scutellariae radix
      attenuates LPS-induced rLSEC activation and HSC migration with downregulation of
      MCP-1 expression. The results provide supporting evidence that Scutellariae radix
      may be beneficial for the amelioration of liver fibrosis.

PMID- 24036166
TI  - Selective reduction of excitatory hippocampal sharp waves by docosahexaenoic acid
      and its methyl ester analog ex-vivo.
AB  - Excitatory sharp waves (SPWs) originating from the hippocampus are considered to
      model the interictal "spikes" that occur in people with temporal lobe epilepsy.
      Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid that has been
      reported to reduce neuronal excitability in vitro. The effect of DHA on
      hippocampal SPWs, however, is not known. Our goal was to determine whether DHA
      suppresses SPWs in thick mouse hippocampal slices, and to compare its effects
      with those of oleic acid (OA, control) and the standard anticonvulsant
      carbamazepine (CBZ). Also tested, were DHA's structural PUFA analogs n-3
      docosapentaenoic acid (n-3 DPA), n-6 docosapentaenoic acid (n-6 DPA) and DHA
      methyl ester (DHA-Me). The possible involvement of GABAergic activity was also
      examined using GABA receptor blockers. Extracellular recordings from CA1 and CA3
      regions in hippocampal slices revealed that DHA reduced the incidence of SPWs.
      CBZ also reduced the incidence of SPWs and was 5 time more potent than DHA. DHA's
      effects on SPWs was abolished in the presence of GABA-receptor blockers,
      suggesting involvement of the GABA system in reducing excitatory SPWs. (14)C-DHA
      application to the slices confirmed the incorporation of DHA into membrane
      phospholipids. N-3 DPA and n-6 DPA, however, which also incorporate into
      phospholipids, had no effect on SPWs, while DHA-Me, a DHA analog that does not
      incorporate into membrane phospholipids, was effective at reducing them. We
      conclude that DHA, but not its n-3 and n-6 analogs, reduces network excitability
      of the recurrent CA3 circuitry in the mouse hippocampus. This reduction may be
      mediated by DHA in its unesterified form, and is likely related to a modulatory
      effect of DHA on GABAergic activity. 

PMID- 24036167
TI  - A Poisson-lognormal conditional-autoregressive model for multivariate spatial
      analysis of pedestrian crash counts across neighborhoods.
AB  - This work examines the relationship between 3-year pedestrian crash counts across
      Census tracts in Austin, Texas, and various land use, network, and demographic
      attributes, such as land use balance, residents' access to commercial land uses,
      sidewalk density, lane-mile densities (by roadway class), and population and
      employment densities (by type). The model specification allows for region
      specific heterogeneity, correlation across response types, and spatial
      autocorrelation via a Poisson-based multivariate conditional auto-regressive
      (CAR) framework and is estimated using Bayesian Markov chain Monte Carlo methods.
      Least-squares regression estimates of walk-miles traveled per zone serve as the
      exposure measure. Here, the Poisson-lognormal multivariate CAR model outperforms
      an aspatial Poisson-lognormal multivariate model and a spatial model (without
      cross-severity correlation), both in terms of fit and inference. Positive spatial
      autocorrelation emerges across neighborhoods, as expected (due to latent
      heterogeneity or missing variables that trend in space, resulting in spatial
      clustering of crash counts). In comparison, the positive aspatial, bivariate
      cross correlation of severe (fatal or incapacitating) and non-severe crash rates
      reflects latent covariates that have impacts across severity levels but are more
      local in nature (such as lighting conditions and local sight obstructions), along
      with spatially lagged cross correlation. Results also suggest greater mixing of
      residences and commercial land uses is associated with higher pedestrian crash
      risk across different severity levels, ceteris paribus, presumably since such
      access produces more potential conflicts between pedestrian and vehicle
      movements. Interestingly, network densities show variable effects, and sidewalk
      provision is associated with lower severe-crash rates. 

PMID- 24036168
TI  - Single prolonged stress impairs social and object novelty recognition in rats.
AB  - Posttraumatic stress disorder (PTSD) results from exposure to a traumatic event
      and manifests as re-experiencing, arousal, avoidance, and negative cognition/mood
      symptoms. Avoidant symptoms, as well as the newly defined negative
      cognitions/mood, are a serious complication leading to diminished interest in
      once important or positive activities, such as social interaction; however, the
      basis of these symptoms remains poorly understood. PTSD patients also exhibit
      impaired object and social recognition, which may underlie the avoidance and
      symptoms of negative cognition, such as social estrangement or diminished
      interest in activities. Previous studies have demonstrated that single prolonged
      stress (SPS), models PTSD phenotypes, including impairments in learning and
      memory. Therefore, it was hypothesized that SPS would impair social and object
      recognition memory. Male Sprague Dawley rats were exposed to SPS then tested in
      the social choice test (SCT) or novel object recognition test (NOR). These tests
      measure recognition of novelty over familiarity, a natural preference of rodents.
      Results show that SPS impaired preference for both social and object novelty. In
      addition, SPS impairment in social recognition may be caused by impaired
      behavioral flexibility, or an inability to shift behavior during the SCT. These
      results demonstrate that traumatic stress can impair social and object
      recognition memory, which may underlie certain avoidant symptoms or negative
      cognition in PTSD and be related to impaired behavioral flexibility. 

PMID- 24036169
TI  - Voluntary aerobic exercise increases the cognitive enhancing effects of working
      memory training.
AB  - Increases in performance on tests of attention and learning are often observed
      shortly after a period of aerobic exercise, and evidence suggests that humans who
      engage in regular exercise are partially protected from age-related cognitive
      decline. However, the cognitive benefits of exercise are typically short-lived,
      limiting the practical application of these observations. Here, we explored
      whether physical exercise might induce lasting changes in general cognitive
      ability if that exercise was combined with working memory training, which is
      purported to broadly impact cognitive performance. Mice received either exercise
      treatment (6 weeks of voluntary running wheel access), working memory training
      (in a dual radial-arm maze), both treatments, or various control treatments.
      After this period of exercise, working memory training was initiated (alternating
      with days of exercise), and continued for several weeks. Upon completion of these
      treatments, animals were assessed (2-4 weeks later) for performance on four
      diverse learning tasks, and the aggregate performance of individual animals
      across all four learning tasks was estimated. Working memory training alone
      promoted small increases in general cognitive performance, although any
      beneficial effects of exercise alone had dissipated by the time of learning
      assessments. However, the two treatments in combination more than doubled the
      improvement in general cognitive performance supported by working memory training
      alone. Unlike the transient effects that acute aerobic exercise can have on
      isolated learning tasks, these results indicate that an acute period of exercise
      combined with working memory training can have synergistic and lasting impact on
      general cognitive performance. 

PMID- 24036170
TI  - Alpha1-adrenergic drugs affect the development and expression of ethanol-induced
      behavioral sensitization.
AB  - BACKGROUND: According to the incentive sensitization theory, addiction is caused
      primarily by drug-induced sensitization in the brain mesocorticolimbic systems.
      After repeated ethanol administration, some animals develop psychomotor
      sensitization, a phenomenon which occurs simultaneously with the incentive
      sensitization. Recent evidence suggests the involvement of norepinephrine (NE) in
      drug addiction, with a critical role in the ethanol reinforcing properties. In
      this study we evaluated the influence of an agonist (phenylephrine) and an
      antagonist (prazosin) of alpha1-adrenergic receptors on the development and
      expression of behavioral sensitization to ethanol. Male Swiss mice, previously
      treated with ethanol or saline, were challenged with the combined administration
      of ethanol (or saline) with alpha1-adrenergic drugs. Prazosin (0.1; 0.5 and 1.0
      mg/kg) and phenylephrine (1.0 and 2.0 mg/kg) administration blocked the
      expression of behavioral sensitization to ethanol. In another set of experiments,
      mice treated with 0.5mg/kg of prazosin+ethanol did not present the development of
      behavioral sensitization. However, when challenged with ethanol alone, they
      showed the same sensitized levels of locomotor activity of those presented by
      mice previously treated with ethanol and saline. Phenylephrine (1.0 mg/kg)
      treatment did not affect the development of behavioral sensitization. Based on
      this data, we concluded that the alteration of alpha1-adrenergic receptors
      functioning, by the administration agonists or antagonists, affected the
      locomotor sensitization to the stimulant effect of ethanol, suggesting that the
      normal functioning of the noradrenergic system is essential to its development
      and expression.

PMID- 24036171
TI  - The role of the 5'-cap structure in viral ribonucleoproteins assembly from potato
      virus X coat protein and RNAs.
AB  - The potato virus X (PVX) virion can be reconstituted in vitro from the virus coat
      protein (CP) and RNA; heterologous RNAs may be used as well. In our recent study,
      structure and properties of cognate and heterologous viral ribonucleoproteins
      (vRNPs) were demonstrated to be similar to those of native virions. The assembly
      was found to be initiated at the 5' terminus of an RNA and was not dependent on
      RNA sequence. The aim of the present study was to search for a signal or an
      essential structural element that directs packaging of viral genetic material
      into vRNPs. vRNPs were formed by incubation of the PVX CP with heterologous
      capped RNAs, their functional fragments lacking the cap structure, as well as the
      capped and uncapped transcripts corresponding to the 5'-terminal region of the
      genomic PVX RNA. Experimental data show that the presence of the cap structure at
      the 5' end of a nucleic acid is an important condition for vRNP assembly from RNA
      and CP. Presumably, the 5'-cap affects conformational state of the RNA region
      responsible for the efficient interaction with CP and creates conformational
      encapsidation signal for vRNP assembly.

PMID- 24036172
TI  - Effects of blood-feeding on olfactory sensitivity of the malaria mosquito
      Anopheles gambiae: application of mixed linear models to account for repeated
      measurements.
AB  - Olfaction plays an important role in the host-seeking behavior of the malaria
      mosquito Anopheles gambiae. After a complete blood meal, female mosquitoes will
      not engage in host-seeking behavior until oviposition has occurred. We
      investigated if peripheral olfactory sensitivity changed after a blood meal by
      recording electroantennograms (EAGs) of female mosquitoes at three time points
      (2h, 48 h and 72 h) to 15 volatile kairomones of either human origin or
      documented to emanate from oviposition sites. The EAG-sensitivity was compared
      with that of females of similar age post eclosion. As is common practice in
      electrophysiological studies, the EAG recordings were obtained by repeated
      stimulation of the same antennal preparations. We introduce mixed linear modeling
      as an improved statistical analysis for electrophysiological data. Two hours
      after blood ingestion, olfactory sensitivity as quantified through EAG-recording
      increased significantly and selectively, i.e. for seven compounds, compared to
      unfed females of the same age. Such short-term electrophysiological sensitization
      in the olfactory system as a result of feeding has not been documented before for
      insects. Sensitization to six compounds persisted until 48 h or 72 h post-blood
      meal at one or more concentrations. Desensitization was observed at 48 and 72 h
      pbm in response to two and three kairomones, respectively. For several compounds,
      sensitization at the EAG-level corresponded with sensitization found previously
      in single sensillum studies on olfactory neurons in antennal sensilla trichodea
      of An. gambiae females. These effects are likely to reflect sensitization to
      oviposition cues, as eggs have matured 48-72 h pbm. Knowledge of changes in
      olfactory sensitivity to kairomones can be applied to increase trap catches of
      malaria mosquitoes that have taken a blood meal and need to locate oviposition
      sites.

PMID- 24036173
TI  - The breaking of a delayed ring neural network contributes to stability: The rule
      and exceptions.
AB  - We prove that in our mathematical model the breaking of a delayed ring neural
      network extends the stability region in the parameters space, if the number of
      the neurons is sufficiently large. If the number of neurons is small, then a
      "paradoxical" region exists in the parameters space, wherein the ring neural
      configuration is stable, while the linear one is unstable. We study the
      conditions under which the paradoxical region is nonempty. We discuss how our
      mathematical modeling reflects neurosurgical operations with the severing of
      particular connections in the brain.

PMID- 24036174
TI  - Recognition of sulphated and fucosylated receptor sialosides by
      A/Vietnam/1194/2004 (H5N1) influenza virus.

PMID- 24036175
TI  - Mutation of the Theiler's virus leader protein zinc-finger domain impairs
      apoptotic activity in murine macrophages.
AB  - The Theiler's murine encephalomyelitis virus (TMEV) leader (L) protein zinc
      finger domain was mutated to study its role in cell death in infection of the
      murine macrophage cell line M1-D, revealing that an intact zinc-finger domain is
      required for full apoptotic activity. A functional L zinc-finger domain was also
      required for activation of p38 MAPK that results in phosphorylation and
      activation of p53, and in turn, alteration of the conformation of the anti
      apoptotic proteins Puma and Mcl-1, leading to the release of pro-apoptotic Bax
      and apoptosis through the intrinsic pathway. TMEV infection also inhibits host
      protein synthesis, a stress shown by others to induce apoptosis. Since inhibition
      of host protein synthesis follows rather than precedes activation of MKK3/6 and
      p38, it seems less likely that it triggers apoptosis in infected cells. Finally,
      we showed that the levels of reactive oxygen species following infection were
      consistent with apoptotic rather than necrotic cell death. Thus, these
      experiments support an important role for the TMEV L protein zinc-finger domain
      in apoptosis in an infected murine macrophage line.

PMID- 24036176
TI  - Determination of amantadine and rimantadine in chicken muscle by QuEChERS
      pretreatment method and UHPLC coupled with LTQ Orbitrap mass spectrometry.
AB  - A novel sample pretreatment method was developed for the quantitative
      determination of amantadine and rimantadine in chicken muscle tissues by ultra
      high performance liquid chromatography coupled with high resolution LTQ Orbitrap
      mass spectrometry (UHPLC-LTQ Orbitrap MS). The samples were pretreated by
      modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method, using
      acetonitrile (1% acetic acid, v/v) as extraction solution and C18 sorbent for
      clean-up. The separation was carried out on a Waters ACQUITY UPLC HSS T3 column
      (150mm*2.1mm, 1.8MUm particle), using a mobile phase of acetonitrile and 0.1%
      aqueous formic acid solution. LTQ Orbitrap MS with resolving power of 60000 was
      applied for analysis of the samples. Amantadine and rimantadine were identified
      from their accurate mass (within 5ppm) and retention times from the acquired full
      scan chromatogram and quantified by their peak areas. The linear range for the
      determination of the analytes was 1-100MUg/kg. Limits of detection (LODs) for
      amantadine and rimantadine were 1.02MUg/kg and 0.67MUg/kg, respectively. The
      intra- and inter-day accuracy ranged from 87.5% to 102.4%, and 82.5% to 105.8%
      for amantadine, and 95.3% to 97.4%, and 89.4% to 93.2% for rimantadine,
      respectively. The precision of intra- and inter-day was between 3.9-6.3% and 5.95
      13.9% for amantadine, 6.0-7.45% and 7.8-12.4% for rimantadine, respectively.
      Finally, the method was applied for the determination of these antiviral agents
      in routine samples, and amantadine residue was detected in some cases. 

PMID- 24036177
TI  - Analysis of non-esterified fatty acids in human samples by solid-phase-extraction
      and gas chromatography/mass spectrometry.
AB  - The determination of the fatty acid (FA) profile of lipid classes is essential
      for lipidomic analysis. We recently developed a GC/MS-method for the analysis of
      the FA profile of total FAs, i.e. the totality of bound and unbound FAs, in any
      given biological sample (TOFAs). Here, we present a method for the analysis of
      non-esterified fatty acids (NEFAs) in biological samples, i.e. the fraction that
      is present as extractable free fatty acids. Lipid extraction is performed
      according to Dole using 80/20 2-propanol/n-hexane (v/v), with 0.1% H2SO4. The
      fatty acid-species composition of this NEFA-fraction is determined as FAME after
      derivatization with our GC/MS-method on a BPX column (Shimadzu). Validation of
      the NEFA-method presented was performed in human plasma samples. The validated
      method has been used with human plasma, cells and tissues, as well as mammalian
      body fluids and tissue samples. The newly developed solid-phase-extraction (SPE)
      GC-MS method allows the rapid separation of the NEFA-fraction from a neutral
      lipid extract of plasma samples. As a major advantage compared to G-FID-methods,
      GC-MS allows the use of stable isotope labeled fatty acid precursors to monitor
      fatty acid metabolism. 

PMID- 24036178
TI  - Optoelectronic plethysmography: intra-rater and inter-rater reliability in
      healthy subjects.
AB  - Optoelectronic plethysmography (OEP) has been used to measure changes in chest
      wall volume and its compartments. However, literature lacks research on its
      reliability. The purpose of this study was to evaluate the intra-rater and inter
      rater reliability of OEP. Thirty-two healthy subjects were evaluated at rest and
      during submaximal exercise on a cycle ergometer. The following variables were
      assessed: chest wall volume (VCW); percentage contribution of the pulmonary rib
      cage (V(rcp)%), abdominal rib cage (V(rca)%), rib cage (V(rc)%) and abdomen
      (Vab%); chest wall end-expiratory volume (Vee(cw)); chest wall end-inspiratory
      volume (Vei(cw)); ratio of inspiratory time to total time of the respiratory
      cycle (Ti/T(tot)); respiratory rate (f) and mean inspiratory flow (V(cw)/Ti).
      Intraclass correlation coefficient (ICC) and coefficient of variation of Method
      Error (CV(ME)) were used to evaluate reliability. Results showed ICC values
      higher than 0.75 and CV(ME) values less than 10% for most variables at rest and
      during exercise indicating that OEP is a reliable instrument to assess chest wall
      volumes at rest and during exercise in healthy subjects.

PMID- 24036179
TI  - Alcohol consumption promotes the intestinal translocation of Streptococcus suis
      infections.
AB  - Streptococcus suis is an emerging zoonotic agent. This study aimed to investigate
      whether S. suis is likely to translocate across the intestines of human hosts who
      have liver disease and/or consume alcohol. Both the alcoholism and cirrhosis
      models exhibited high mRNA expression of TGF and collagen1, but only the
      cirrhosis model had fibrosis in the liver. After both models were infected with
      S. suis, significantly different concentrations of S. suis were detected in the
      blood and brains of the alcoholism model (Blood: 36.4%; Brain: 31.8%) and the
      cirrhosis model (Blood: 62.5%; Brain: 62.5%) compared to the concentrations in
      the healthy mice (Blood: 15.4%; Brain: 0%). Trans-epithelial electrical
      resistance (TER) was used to examine the Caco-2 cells in the in vitro that had an
      S. suis infection combined with 1% ethanol. Although the ethanol did not
      influence the Caco-2 cells' barriers, it did rapidly decrease the barriers' TER
      value and then their E-cadherin compared to the infected Caco-2 cells without the
      ethanol treatment. Immunofluorescence also indicated that the barriers of the
      Caco-2 cells treated with ethanol were disrupted and that S. suis translocated
      from the apical to the basolateral side. This study demonstrated that alcohol
      consumption helped S. suis to translocate. 

PMID- 24036180
TI  - Identification of secretory immunoglobulin A antibody targets from human milk in
      cultured cells infected with enteropathogenic Escherichia coli (EPEC).
AB  - Enteropathogenic Escherichia coli (EPEC) uses a type III secretion system (T3SS)
      to inject effectors into host cells and alter cellular physiology. The aim of the
      present study was to identify targets of human secretory immunoglobulin A (sIgA)
      antibodies from the proteins delivered by EPEC into HEp-2 cells after infection.
      Bacterial proteins delivered into EPEC-infected cells were obtained in sub
      cellular fractions (cytoplasmic, membrane, and cytoskeleton) and probed with sIgA
      antibodies from human milk and analyzed by Western blotting. These sIgA
      antibodies reacted with Tir and EspB in the cytoplasmic and membrane fractions,
      and with intimin in the membrane fraction mainly. The sIgA also identified an
      EPEC surface-associated Heat-shock protein 70 (Hsp70) in HEp-2 cells infected
      with EPEC. Purified Hsp70 from EPEC was able to bind to HEp-2 cells, suggesting
      adhesive properties in this protein. EspC secreted to the medium reacted strongly
      with the sIgA antibodies. An EPEC 115 kDa protein, unrelated to the EspC protein,
      was detected in the cytoplasm of infected HEp-2 cells, suggesting that this is a
      new protein translocated by EPEC. The results suggest that there is a strong host
      antibody response to Tir and intimin, which are essential proteins for attaching
      and effacing (A/E) pathogen mediated disease. 

PMID- 24036181
TI  - Association between virulence factors of helicobacter pylori and gastric mucosal
      interleukin-18 mRNA expression in dyspeptic patients.
AB  - BACKGROUND: Helicobacter pylori (Hp) infection is associated with gastritis and
      marked infiltration of the gastric mucosa by several cytokines secreting
      inflammatory cells that contribute to sustain and expand the local inflammation.
      Different clinical expressions of the infection may reflect distinctive patterns
      of cytokine expression. IL-1beta, TNF-alpha, IL-17 and IL-23 have been reported
      to be involved in Hp-induced gastric mucosal inflammation, but the details and
      association to different patterns of inflammation and virulence factors remain
      unclear. METHODS: Total RNA was extracted from gastric biopsies of 51 Hp-infected
      patients and 44 Hp-negative patients. Mucosal IL-18 mRNA expression in gastric
      biopsies was determined by Real-Time PCR. Presence of virulence factors was
      evaluated using PCR. RESULTS: IL-18 mRNA expression was significantly increased
      in biopsies of Hp-infected patients compared to Hp-uninfected individuals. There
      was no association between virulence factors and IL-18 mRNA expression. Also
      severity of mononuclear infiltration was significantly higher in gastritis
      patients with vacA (m1)-positive compare patients with vacA (m2)-positive.
      CONCLUSIONS: IL-18 may play an important role in the inflammatory response and
      promote the chronic and persistent inflammatory changes in the stomach. This may
      ultimately influence the outcome of Hp-associated diseases that arise within the
      context of gastritis.

PMID- 24036182
TI  - Farrerol regulates antimicrobial peptide expression and reduces Staphylococcus
      aureus internalization into bovine mammary epithelial cells.
AB  - Mastitis, defined as inflammation of the mammary gland, is an infectious disease
      with a major economic influence on dairy industry. Staphylococcus aureus is a
      common gram-positive pathogen that frequently causes subclinical, chronic
      infection of the mammary gland in dairy cows. Farrerol, a traditional Chinese
      medicine isolated from rhododendron, has been shown to have anti-bacterial
      activity. However, the effect of farrerol on S. aureus infection in mammary
      epithelium has not been studied in detail. The aim of this study was to
      investigate the effect of farrerol on the invasion of bovine mammary epithelial
      cells (bMEC) by S. aureus. The expression of antimicrobial peptide genes by bMEC
      were assessed in the presence or absence of S. aureus infection. Our results
      demonstrated that farrerol (4-16 MUg/ml) reduced > 55% the internalization of S.
      aureus into bMEC. We also found that farrerol was able to down-regulate the mRNA
      expression of tracheal antimicrobial peptide (TAP) and bovine neutrophil beta
      defensin 5 (BNBD5) in bMEC infected with S. aureus. The Nitric oxide (NO)
      production of bMEC after S. aureus stimulation was decreased by farrerol
      treatment. Furthermore, farrerol treatment suppressed S. aureus-induced NF-kappaB
      activation in bMEC. These results demonstrated that farrerol modulated TAP and
      BNBD5 gene expression in mammary gland, enhances bMEC defense against S. aureus
      infection and could be useful in protection against bovine mastitis. 

PMID- 24036183
TI  - Repeated toluene exposure increases c-Fos in catecholaminergic cells of the
      nucleus accumbens shell.
AB  - Toluene is a frequently abused solvent. Previous studies have suggested that
      toluene acts like other drugs of abuse, specifically on the dopaminergic system
      in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the mesolimbic
      pathway. Although changes in dopamine (DA) levels and c-Fos have been observed in
      both acute and repeated exposure paradigms, the extent to which c-Fos is
      localized to catecholaminergic cells is unknown. The present study tested the
      effects of repeated toluene exposure (1000-4000ppm) on locomotor activity and
      cells containing c-Fos, tyrosine hydroxylase (TH), or both in the core and shell
      of the NAc, as well as the anterior and posterior VTA. We focused our study on
      adolescents, since adolescence is a time of great neural change and a time when
      individuals tend to be more susceptible to drug abuse. In early tests, toluene
      dose-dependently increased locomotor activity. Repeated exposure to the highest
      concentration of toluene resulted in sensitization to toluene's effects on
      locomotor activity. Although the number of cells immunopositive for c-Fos or TH
      did not significantly differ across groups, cells immunopositive for TH+c-Fos
      were higher in the NAc shell of animals exposed to 4000ppm than in animals
      exposed to air (control) or 1000ppm. Taken together, these findings demonstrate
      that repeated high dose toluene exposure increases locomotor activity as well as
      activation of catecholaminergic cells in the shell of the NAc. 

PMID- 24036184
TI  - Motion-based prediction explains the role of tracking in motion extrapolation.
AB  - During normal viewing, the continuous stream of visual input is regularly
      interrupted, for instance by blinks of the eye. Despite these frequents blanks
      (that is the transient absence of a raw sensory source), the visual system is
      most often able to maintain a continuous representation of motion. For instance,
      it maintains the movement of the eye such as to stabilize the image of an object.
      This ability suggests the existence of a generic neural mechanism of motion
      extrapolation to deal with fragmented inputs. In this paper, we have modeled how
      the visual system may extrapolate the trajectory of an object during a blank
      using motion-based prediction. This implies that using a prior on the coherency
      of motion, the system may integrate previous motion information even in the
      absence of a stimulus. In order to compare with experimental results, we
      simulated tracking velocity responses. We found that the response of the motion
      integration process to a blanked trajectory pauses at the onset of the blank, but
      that it quickly recovers the information on the trajectory after reappearance.
      This is compatible with behavioral and neural observations on motion
      extrapolation. To understand these mechanisms, we have recorded the response of
      the model to a noisy stimulus. Crucially, we found that motion-based prediction
      acted at the global level as a gain control mechanism and that we could switch
      from a smooth regime to a binary tracking behavior where the dot is tracked or
      lost. Our results imply that a local prior implementing motion-based prediction
      is sufficient to explain a large range of neural and behavioral results at a more
      global level. We show that the tracking behavior deteriorates for sensory noise
      levels higher than a certain value, where motion coherency and predictability
      fail to hold longer. In particular, we found that motion-based prediction leads
      to the emergence of a tracking behavior only when enough information from the
      trajectory has been accumulated. Then, during tracking, trajectory estimation is
      robust to blanks even in the presence of relatively high levels of noise.
      Moreover, we found that tracking is necessary for motion extrapolation, this
      calls for further experimental work exploring the role of noise in motion
      extrapolation. 

PMID- 24036185
TI  - Synthesis and solvent-dependent photochromic reactions of porphyrin-spiropyran
      hybrid compounds.
AB  - Porphyrin(Por)-spiropyran(SP) hybrid compounds, including Por-SP dyad, Por-SP2
      triad, and Por-SP4 pentad, were prepared and characterized by (1)H NMR, MALDI-TOF
      MS and UV-Vis spectroscopies. Upon 350 nm UV irradiation of Por-SPn (n=1, 2, 4)
      in dichloromethane, unusual red-shifted absorption spectra were observed with the
      colour change from pink into green. Probably due to the protonation of core
      nitrogens in porphyrin ring, their absorption maxima in dichloromethane were
      shifted from 418 (Soret band), 515, 550, 590, 645 (four Q bands) nm into 450 and
      665 nm. Also, fluorescence maxima were also shifted from 650 and 715 nm to 692
      nm. In the other hands, upon irradiation with 350nm UV light in THF, the colour
      changed from pink into violet and absorption band at 590 nm increased and the
      fluorescence spectra showed the decrease of 650 and 715 nm bands and increase of
      600-640 nm band, due to the normal ring-opening reaction of spiropyran moiety
      into merocyanine. In the dark, original absorption and fluorescence spectra were
      recovered very slowly in dichloromethane, but quickly in THF. The reversible
      photochromic reactions of Por-SPn (n=1, 2, 4) in dichloromethane and THF were
      investigated by observing absorption and fluorescence spectral changes during UV
      irradiation or standing in the dark.

PMID- 24036186
TI  - Molecular mechanics force field-based general map for the solvation effect on
      amide I probe of peptide in different micro-environments.
AB  - A general electrostatic potential map based on molecular mechanics force field
      for modeling the amide I frequency is presented. This map is applied to N
      methylacetamide (NMA) and designed to be transferable in different micro
      environments. The electrostatic potentials from solvent and peptide side chain
      are projected on the amide unit of NMA to induce the frequency shift of amide I
      mode. It is shown that the predicted amide I frequency reproduces the
      experimental data satisfactorily, especially when NMA in polar solvents. The
      amide I frequency shift is largely determined by the solvents in aqueous solution
      while it is dominated by the local structure of peptide in other solvent
      environments. The map parameters are further applied on NMA-MeOH system and the
      obtained IR spectra show doublet peak profile with negligible deviation from the
      experimental data, suggesting the usefulness of this general map for providing
      information about vibrational parameters of amide motions of peptide in different
      environments. 

PMID- 24036187
TI  - Are associations between the perceived home and neighbourhood environment and
      children's physical activity and sedentary behaviour moderated by urban/rural
      location?
AB  - Associations between parental perceived home and neighbourhood environments and
      children's physical activity (PA), and sedentary time (ST) and screen time and
      moderating effects according to urban/rural location were examined. Data were
      collected (2007-2008) from a cohort of women (aged 18-45 years) and their
      children (5-12 years) participating in the Resilience for Eating and Activity
      Despite Inequality (READI) study. A total of 613 children (47% boys; mean age
      9.4+/-2.2 years) and their mothers were included in the study. Urban children had
      higher screen time than rural children. Mothers in rural areas reported greater
      access to physical activity equipment in the home, higher levels of descriptive
      norms for physical activity, greater knowledge of the neighbourhood, a stronger
      social network, and higher personal safety than urban mothers. There were five
      significant interactions between the home and neighbourhood environment and PA/ST
      according to urban/rural location. Among urban children, the importance of doing
      PA together as a family was positively associated with ST. Interventions
      targeting PA and ST may need to target different factors according to urban/rural
      location. 

PMID- 24036188
TI  - A sudden onset and the spontaneous remission of severe hypo-high-density
      lipoprotein cholesterolemia without serious underlying disease: a case report.
AB  - BACKGROUND: Severe hypo-high-density lipoprotein (HDL) cholesterolemia is defined
      by serum values less than 20mg/dl. Few acquired cases, without serious underlying
      disease, have been reported. CASE: An asymptomatic 75-y-old man was admitted for
      evaluation of low serum HDL-cholesterol (HDL-C) levels (2-8 mg/dl). The record of
      periodic medical examinations revealed that a sudden decrease had occurred 5 y
      ago. Mild anemia and proteinuria were noted but the liver and thyroid function
      tests were normal. beta-Quantification revealed a relatively low HDL-C (10.8
      mg/dl) and the serum lecithin cholesterol acyltransferase (LCAT) activity was low
      (29.4 nmol/ml/h). Unexpectedly, serum HDL-C levels recovered 2 y after hospital
      discharge. In addition, the serum LCAT activity, hemoglobin concentrations, and
      urine protein tests all returned to within the reference interval. Subsequent
      examinations could not clarify the cause of the sudden onset and spontaneous
      recovery of the extremely low HDL-C. CONCLUSIONS: We describe an unusual case of
      acquired HDL-C deficiency in a 75-y-old man that did not have serious pre
      existing disease. Recently, extremely low HDL-C levels in patients with the
      nephrotic syndrome, associated with acquired LCAT deficiency, have been reported.
      The present case might illustrate a milder form of this disorder, because the
      clinical findings show many similarities.

PMID- 24036189
TI  - Relationships between serum omentin-1 concentration and bone mineral density, and
      bone biochemical markers in Chinese women.
AB  - BACKGROUND: Omentin-1, as a newly discovered adipocytokine, plays an important
      role in bone metabolism. However, the association between circulating omentin-1
      level and bone mineral density (BMD) in Chinese women has never been
      investigated. METHODS: Serum omentin-1, adiponectin, leptin, bone turnover
      biochemical markers, BMD were determined in 225 premenopausal women and 285
      postmenopausal women. RESULTS: In premenopausal Chinese women, omentin-1 level
      was significantly higher compared to postmenopausal women. The multiple linear
      stepwise regression analysis showed that lean mass, omentin-1 and weight were
      independent predictors of BMD in premenopausal women. Omentin-1 was negatively
      correlated with bone-specific alkaline phosphatase (BAP) and bone cross-linked N
      terminal telopeptides of type I collagen (NTX) in premenopausal women. However
      the omentin-1 was not the predictor of BMD in postmenopausal women. CONCLUSIONS:
      Omentin-1 is an independent predictor of BMD in premenopausal Chinese women, and
      shows a negative correlation with bone turnover biochemical markers. Our results
      suggest that omentin-1 may exert a negative effect on bone mass by inhibiting
      bone formation in premenopausal women.

PMID- 24036190
TI  - Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility
      in rats.
AB  - BACKGROUND: Evidence indicates that cardiac hypothyroidism may contribute to
      heart failure progression. It is also known that heart failure is associated with
      an increased risk of atrial fibrillation (AF). Although it is established that
      hyperthyroidism increases AF incidence, the effect of hypothyroidism on AF is
      unclear. This study investigated the effects of different thyroid hormone levels,
      ranging from hypothyroidism to hyperthyroidism on AF inducibility in
      thyroidectomized rats. METHODS AND RESULTS: Thyroidectomized rats with serum
      confirmed hypothyroidism 1 month after surgery were randomized into hypothyroid
      (N=9), euthyroid (N=9), and hyperthyroid (N=9) groups. Rats received placebo, 3.3
      mg l-thyroxine (T4), or 20-mg T4 pellets (60-day release form) for 2 months,
      respectively. At the end of treatment, hypothyroid, euthyroid, and hyperthyroid
      status was confirmed. Hypothyroid animals showed cardiac atrophy and reduced
      cardiac systolic and diastolic functions, whereas hyperthyroid rats exhibited
      cardiac hypertrophy and increased cardiac function. Hypothyroidism and
      hyperthyroidism produced opposite electrophysiological changes in heart rates and
      atrial effective refractory period, but both significantly increased AF
      susceptibility. AF incidence was 78% in hypothyroid, 67% in hyperthyroid, and the
      duration of induced AF was also longer, compared with 11% in the euthyroid group
      (all P<0.05). Hypothyroidism increased atrial interstitial fibrosis, but connexin
      43 was not affected. CONCLUSIONS: Both hypothyroidism and hyperthyroidism lead to
      increased AF vulnerability in a rat thyroidectomy model. Our results stress that
      normal thyroid hormone levels are required to maintain normal cardiac
      electrophysiology and to prevent cardiac arrhythmias and AF.

PMID- 24036192
TI  - Drowning resuscitation requires another state of mind.

PMID- 24036191
TI  - Stark fluorescence spectroscopy reveals two emitting sites in the dissipative
      state of FCP antennas.
AB  - Diatoms are characterized by very efficient photoprotective mechanisms where the
      excess energy is dissipated as heat in the main antenna system constituted by
      fucoxanthin-chlorophyll (Chl) protein complexes (FCPs). We performed Stark
      fluorescence spectroscopy on FCPs in their light-harvesting and energy
      dissipating states. Our results show that two distinct emitting bands are created
      upon induction of energy dissipation in FCPa and possibly in FCPb. More
      specifically one band is characterized by broad red shifted emission above 700nm
      and bears strong similarity with a red shifted band that we detected in the
      dissipative state of the major light-harvesting complex II (LHCII) of plants
      [26]. We discuss the results in the light of different mechanisms proposed to be
      responsible for photosynthetic photoprotection. 

PMID- 24036193
TI  - Measuring non-technical skills of medical emergency teams: an update on the
      validity and reliability of the Team Emergency Assessment Measure (TEAM).
AB  - Medical emergency team performance including non-technical skills, is receiving
      increased attention due to the influences on patient safety. The Team Emergency
      Assessment Measure (TEAM) was developed to enable standardized performance
      assessment and structured team debriefing. From several studies, the TEAM has
      demonstrated a substantial body of normative data confirming its validity and
      reliability. This includes high uni-dimensional validity, significant subscale
      relationships between Teamwork and Leadership and between Teamwork and Task
      Management (p<0.001), a Cronbach alpha of 0.92 and adequate construct validity.
      The tool has potential for team training to improve team's non-technical
      performance. Further testing is required in 'real' clinical settings. 

PMID- 24036194
TI  - The formula for survival. What's in a number?

PMID- 24036195
TI  - Confirmation of intraosseous cannula placement based on pressure measured at the
      cannula during squeezing the extremity in a piglet model.
AB  - AIM OF THE STUDY: We sought to assess the reliability of the method using the
      pressure measured at the intraosseous (IO) cannula while squeezing the involved
      limb (P(squeezing)) in determining the position of the IO needle and to compare
      its performance with that of the traditional confirmation method. METHODS: Eighty
      limbs of twenty domestic swine were assigned to one of three conditions regarding
      the position of the IO needle; correct placement (n=40), incorrect placement in
      which the IO needle was placed into the subcutaneous space without entering the
      bone (incorrect-subcutaneous placement, n=20), or incorrect placement in which
      the IO needle passed entirely through the bone (incorrect-penetrating placement,
      n=20). A blinded investigator randomly identified the position of the needle by
      the traditional method or test method using P(squeezing). If P(squeezing) was 80
      mmHg or higher, the IO cannula was regarded as incorrectly placed. RESULTS:
      P(squeezing) was higher in incorrect placements (176.0 mmHg (130.0-195.0))
      compared with that in correct placements (27.0 mmHg (20.0-34.0)) (p<0.001). The
      test method correctly identified all 40 placements, but the traditional method
      was incorrect for one (5%) of 20 correct placements (p=1.000) and 7 (35%) of 20
      incorrect placements (p=0.008). In incorrect placements, false positive results
      occurred mainly in incorrect-penetrating placements. CONCLUSION: We suggest that
      the method using the pressure measured at the IO cannula can be used when there
      is uncertainty about the position of the IO cannula after determination using
      traditional methods.

PMID- 24036196
TI  - Impact of the number of on-scene emergency life-saving technicians and outcomes
      from out-of-hospital cardiac arrest in Osaka City.
AB  - BACKGROUNDS: In Japan, ambulance staffing for cardiac arrest responses consists
      of a 3-person unit with at least one emergency life-saving technician (ELST).
      Recently, the number of ELSTs on ambulances has increased since it is believed
      that this improves the quality of on-scene care leading to better outcomes from
      out-of-hospital cardiac arrest (OHCA). The objective of this study was to
      evaluate the association between the number of on-scene ELSTs and OHCA outcome.
      METHODS: This was a prospective cohort study of all bystander-witnessed OHCA
      patients aged >= 18 years in Osaka City from January 2005 to December 2007 using
      on an Utstein-style database. The primary outcome measure was one-month survival
      with favorable neurological outcome defined as a cerebral performance category <=
      2. Multivariable logistic regression model were used to assess the contribution
      of the number of on-scene ELSTs to the outcome after adjusting for confounders.
      RESULTS: Of the 2408 bystander-witnessed OHCA patients, one ELST group was
      present in 639 (26.5%), two ELST were present in 1357 (56.4%), and three ELST
      group in 412 (17.1%). The three ELST group had a significantly higher rate of one
      month survival with favorable neurological outcome compared with the one ELST
      group (8.0% versus 4.5%, adjusted OR 2.26, 95% CI 1.27-4.04), while the two ELST
      group did not (5.4% versus 4.5%, adjusted OR 1.34, 95% CI 0.82-2.19).
      CONCLUSIONS: Compared with the one on-scene ELST group, the three on-scene ELST
      group was associated with the improved one-month survival with favorable
      neurological outcome from OHCA in Osaka City.

PMID- 24036197
TI  - Can survival from out-of-hospital cardiac arrest be predicted from a victim's
      carbon emissions?

PMID- 24036198
TI  - Biocompatible gelatin nanoparticles for tumor-targeted delivery of polymerized
      siRNA in tumor-bearing mice.
AB  - Structural modifications of the siRNA backbone improved its physiochemical
      properties for incorporating in gene carriers without loss of gene-silencing
      efficacy. These modifications provide a wider variety of choice of vector systems
      for siRNA delivery. We developed a tumor-targeted siRNA delivery system using
      polymerized siRNA (poly-siRNA) and natural polymer gelatin. The polymerized siRNA
      (poly-siRNA) was prepared through self-polymerization of thiol groups at the 5'
      end of sense and anti-sense strands of siRNA and was encapsulated in the self
      assembled thiolated gelatin (tGel) nanoparticles (NPs) with chemical cross
      linking. The resulting poly-siRNA-tGel (psi-tGel) nanoparticles (average of 145
      nm in diameter) protect siRNA molecules from enzymatic degradation, and can be
      reversibly reduced to release functional siRNA molecules in reductive conditions.
      The psi-tGel NPs presented efficient siRNA delivery in red fluorescence protein
      expressing melanoma cells (RFP/B16F10) to down-regulate target gene expression.
      In addition, the NPs showed low toxicity at a high transfection dose of 125
      MUg/ml psi-tGel NPs, which included 1 MUM of siRNA molecules. In tumor-bearing
      mice, the psi-tGel NPs showed 2.8 times higher tumor accumulation than the naked
      poly-siRNA, suggesting tumor-targeted siRNA delivery of psi-tGel NPs.
      Importantly, the psi-tGel NPs induced effective tumor RFP gene silencing in vivo
      without remarkable toxicity. The psi-tGel NPs have great potential for a systemic
      siRNA delivery system for cancer therapy, based on their characteristics of low
      toxicity, tumor accumulation, and effective siRNA delivery.

PMID- 24036199
TI  - Longitudinal methods to investigate the role of health determinants in the
      dynamics of income-related health inequality.
AB  - The usual starting point for understanding changes in income-related health
      inequality (IRHI) over time has been regression-based decomposition procedures
      for the health concentration index. However the reliance on repeated cross
      sectional analysis for this purpose prevents both the appropriate specification
      of the health function as a dynamic model and the identification of important
      determinants of the transition processes underlying IRHI changes such as those
      relating to mortality. This paper overcomes these limitations by developing
      alternative longitudinal procedures to analyse the role of health determinants in
      driving changes in IRHI through both morbidity changes and mortality, with our
      dynamic modelling framework also serving to identify their contribution to long
      run or structural IRHI. The approach is illustrated by an empirical analysis of
      the causes of the increase in IRHI in Great Britain between 1999 and 2004. 

PMID- 24036200
TI  - Cell chip with a thiolated chitosan self-assembled monolayer to detect the
      effects of anticancer drugs on breast normal and cancer cells.
AB  - Cell-based chips are an effective in vitro analysis tool; however, the
      sensitivity of the cell chip to biomaterials is high, which is crucial for
      immobilizing cells on the electrode surface without conductivity. In this study,
      we report on a cell chip with a thiolated chitosan monolayer that was easy to
      fabricate, highly adhesive to cells, and enhanced electrochemical signals.
      Thiolated chitosan containing thiol groups was synthesized and self-assembled on
      a gold electrode to immobilize cells, and showed superior electrochemical
      performance to that of poly-l-lysine and collagen. Cyclic voltammetry (CV) was
      performed to distinguish the redox characteristics of normal (HMEC) and breast
      cancer cells (MCF-7); then, two anticancer drugs (doxorubicin and
      cyclophosphamide) were added to the cell cultures to analyze their effects on the
      redox environment of normal and cancer cells derived from the same origin. As a
      result, the CV cathode peaks decreased differently with respect to the cell line
      (normal and cancer) and anticancer drug, which was validated by a conventional
      MTT viability assay. Hence, the proposed cell chip with a thiolated chitosan
      modified layer could be used in various fields, including discriminating normal
      from cancer cells, to evaluating the efficiency of newly developed drugs, and to
      assessing cytotoxicity of various chemicals. 

PMID- 24036201
TI  - Enantiopure dihalocyclopropyl alcohols and esters by lipase catalyzed kinetic
      resolution.
AB  - Four halogenated cyclopropane derivatives with a side chain containing a primary
      (1 and 2) or secondary (3 and 4) alcohol moiety were subject to kinetic
      resolution catalyzed by lipases. Two of them containing secondary alcohol groups
      gave excellent results with Candida antarctica lipase B with E-values around
      1000. Two enantiopure alcohols and two enantiopure butanoates are described:
      (1S,1'S)-1-(2',2'-dichloro-3',3'-dimethylcyclopropyl) ethanol (3), the
      corresponding (1R,1'R)-butanoate (3b) and (1S,1'S)-1-(1'-methyl-2',2'
      dibromocyclopropyl) ethanol (4) and the corresponding (1R,1'R)-butanoate (4b). 

PMID- 24036202
TI  - A process-dissociation analysis of semantic illusions.
AB  - We examine semantic illusions from a dual-process perspective according to which
      the processes that go into failing or succeeding to detect such illusions can be
      decomposed into controlled processes (checking the facts in the sentence against
      the information in memory) and automatic processes (the impression of truth that
      comes from the semantic associations between the elements in the sentence). These
      processes, we argue, make largely independent contributions to truth judgments
      about semantic-illusory sentences. The Process Dissociation Procedure was used to
      obtain estimates of these two kinds of processes. In Study 1, participants judged
      whether sentences were true or false while under high or low cognitive load.
      Cognitive load increased the rate of semantic illusions by specifically affecting
      controlled processing but not automatic processing. In Study 2, a previous paired
      associate learning task also increased the rate of semantic illusions, but it did
      so by specifically affecting automatic processing, not controlled processing. 

PMID- 24036203
TI  - On the competitive uptake and transport of ions through differentiated root
      tissues.
AB  - We simulate the competitive uptake and transport of a mixed salt system in the
      differentiated tissues of plant roots. The results are based on a physical model
      that includes both forced diffusion and convection by the transpiration stream.
      The influence of the Casparian strip on regulating apoplastic flow, the focus of
      the paper, is modelled by varying ion diffusive permeabilities, hydraulic
      reflection coefficients and water permeability for transport across the
      endodermis-pericycle interface. We find that reducing diffusive permeabilities
      leads to significantly altered ion concentration profiles in the pericycle and
      vascular cylinder regions, while increased convective reflectivities affect
      predominantly ion concentrations in the cortex and endodermis tissues. The self
      consistent electric field arising from ion separation is a major influence on
      predicted ion fluxes and accumulation rates. 

PMID- 24036204
TI  - The application of temporal difference learning in optimal diet models.
AB  - An experience-based aversive learning model of foraging behaviour in uncertain
      environments is presented. We use Q-learning as a model-free implementation of
      Temporal difference learning motivated by growing evidence for neural correlates
      in natural reinforcement settings. The predator has the choice of including an
      aposematic prey in its diet or to forage on alternative food sources. We show how
      the predator's foraging behaviour and energy intake depend on toxicity of the
      defended prey and the presence of Batesian mimics. We introduce the precondition
      of exploration of the action space for successful aversion formation and show how
      it predicts foraging behaviour in the presence of conflicting rewards which is
      conditionally suboptimal in a fixed environment but allows better adaptation in
      changing environments. 

PMID- 24036205
TI  - Individual-based chaos: extensions of the discrete logistic model.
AB  - Simple models of density-dependent population growth such as the discrete
      logistic map provide powerful demonstrations of complex population dynamics. Yet
      it is unclear whether the dynamics observed in such idealized systems would be
      present, under realistic conditions, in the context of demographic stochasticity,
      which is well known to exist in finite natural populations. Here, using a set of
      simple, individual-based models (IBM's) and their population-level iterative map
      counterparts, we computationally investigate the contribution of demographic
      stochasticity to density-dependent population dynamics in a simple model of seed
      production and recruitment. Notably, for a sufficiently large lattice, even in
      the presence of demographic stochasticity, many of the qualitative features of
      these idealized maps - including bifurcations - are still present. Demographic
      stochasticity and the constraints imposed by a finite lattice size appear to
      produce mixed dynamics that are partially stochastic, yet qualitatively similar
      to the deterministic models. The mechanistic assumptions and lattice sizes
      required to generate these dynamics cast doubt on whether they might be
      observable in annual plant populations. Nevertheless, we cannot rule out the
      theoretical possibility that such dynamics might be observable in ecological
      communities having similar mechanistic properties. 

PMID- 24036206
TI  - Introduction to special issue.

PMID- 24036207
TI  - Assessing gene network stability and individual variability in the fathead minnow
      (Pimephales promelas) transcriptome.
AB  - Transcriptomics is increasingly used to assess biological responses to
      environmental stimuli and stressors such as aquatic pollutants. However,
      fundamental studies characterizing individual variability in mRNA levels are
      lacking, which currently limits the use of transcriptomics in environmental
      monitoring assessments. To address individual variability in transcript
      abundance, we performed a meta-analysis on 231 microarrays that were conducted in
      the fathead minnow (FHM), a widely used toxicological model. The mean variability
      for gene probes was ranked from most to least variable based upon the coefficient
      of variation. Transcripts that were the most variable in individual tissues
      included NADH dehydrogenase flavoprotein 1, GTPase IMAP family member 7-like and
      v-set domain-containing T-cell activation inhibitor 1-like while genes encoding
      ribosomal proteins (rpl24 and rpl36), basic transcription factor 3, and nascent
      polypeptide-associated complex alpha subunit were the least variable in
      individuals across a range of microarray experiments. Gene networks that showed
      high variability (based upon the variation in expression of individual members
      within the network) included cell proliferation, metabolism (steroid, lipids, and
      glucose), cell adhesion, vascularization, and regeneration while those that
      showed low variability (more stability) included mRNA and rRNA processing,
      regulation of translational fidelity, RNA splicing, and ribosome biogenesis. Real
      time PCR was conducted on a subset of genes for comparison of variability
      collected from the microarrays. There was a significant positive relationship
      between the two methods when measuring individual variability, suggesting that
      variability detected in microarray data can be used to guide decisions on sample
      sizes for measuring transcripts in real-time PCR experiments. A power analysis
      revealed that measuring estrogen receptor ba (esrba) requires fewer biological
      replicates than that of estrogen receptor bb (esrbb) in the gonad and samples
      sizes required to detect a 50% change for reproductive-related transcripts is
      between 12 and 20. Characterizing individual variability at the molecular level
      will prove necessary as efforts are made toward integrating molecular tools into
      environmental risk assessments. 

PMID- 24036208
TI  - A Bayesian changepoint analysis of ChIP-Seq data of Lamin B.
AB  - The spatial organisation of the chromosomes in the nucleus is influenced by
      chromatin regions binding to the nucleic lamina, i.e., the inner part of the
      nucleic envelope. To investigate the architecture of chromosomes in the
      interphase nucleus, it is thus of high interest to detect such chromatin
      segments. This goal can be achieved by considering the fibrous protein Lamin B as
      a surrogate, since regions of high abundance of Lamin B can indicate chromatin
      segments attached to the nucleic lamina. We analyse ChIP-Seq (Chromatin
      Immunoprecipitation Sequencing) data from an experiment that is designed to
      record Lamin B abundance. We introduce a Bayesian segmentation procedure in which
      a Markov Chain Monte Carlo (MCMC) algorithm is used for inference about the
      desired segmentation. The procedure is based on a Bayesian hierarchical model.
      Inference allows the distinction between regions of high versus low levels of
      Lamin B, and therefore, gives an insight into the binding of the chromatin to the
      nucleic envelope. An implementation of this approach is available in the
      statistical software environment R. This article is part of a special issue
      entitled: Computational proteomics in the post-identification era. Guest Editors:
      Martin Eisenacher and Christian Stephan. 

PMID- 24036209
TI  - Regulation of fetal gene expression in heart failure.
AB  - During the processes leading to adverse cardiac remodeling and heart failure,
      cardiomyocytes react to neurohumoral stimuli and biomechanical stress by
      activating pathways that induce pathological hypertrophy. The gene expression
      patterns and molecular changes observed during cardiac hypertrophic remodeling
      bare resemblance to those observed during fetal cardiac development. The re
      activation of fetal genes in the adult failing heart is a complex biological
      process that involves transcriptional, posttranscriptional and epigenetic
      regulation of the cardiac genome. In this review, the mechanistic actions of
      transcription factors, microRNAs and chromatin remodeling processes in regulating
      fetal gene expression in heart failure are discussed. 

PMID- 24036210
TI  - Homer1 knockdown protects dopamine neurons through regulating calcium homeostasis
      in an in vitro model of Parkinson's disease.
AB  - Homer1 protein is an important scaffold protein at postsynaptic density and has
      been demonstrated to play a central role in calcium signaling in the central
      nervous system. The aim of this study was to investigate the effects of Homer1
      knockdown on MPP(+) induced neuronal injury in cultured dopamine (DA) neurons. We
      found that down-regulating Homer1 expression with specific small interfering RNA
      (siRNA) significantly suppressed LDH release, reduced Propidium iodide (PI) or
      Hoechst staining, increased the number of tyrosine hydroxylase (TH) positive
      cells and DA uptake, and attenuated apoptotic and necrotic cell death after
      MPP(+) injury. Homer1 knockdown decreased intracellular reactive oxygen species
      (ROS) generation through inhibition of intracellular calcium overload, but did
      not affect the endogenous antioxidant enzyme activities. Calcium imaging was used
      to examine the changes of intracellular Ca(2+) concentration ([Ca(2+)]cyt) and
      Ca(2+) in endoplasmic reticulum (ER) ([Ca(2+)]ER), and the results showed that
      Homer1 siRNA transfection attenuated ER Ca(2+) release up to 120min after MPP(+)
      injury. Furthermore, decrease of [Ca(2+)]cyt induced by Homer1 knockdown in
      MPP(+) treated neurons was further enhanced by NMDA receptor antagonists MK-801
      and AP-5, but not canonical transient receptor potential (TRPC) channel
      antagonist SKF-96365. l-type calcium antagonist isradipine but not nimodipine
      further inhibited intracellular calcium overload after MPP(+) insult in Homer1
      down-regulated neurons. These results suggest that Homer1 knockdown has
      protective effects against neuronal injury in in vitro PD model by reducing
      calcium overload mediated ROS generation, and this protection may be dependent at
      least in part on the regulatory effects on the function of calcium channels in
      both plasma membrane and ER. 

PMID- 24036212
TI  - Activation of integrin beta1-focal adhesion kinase-RasGTP pathway plays a
      critical role in TGF beta1-induced podocyte injury.
AB  - The depletion of glomerular podocytes is the key mechanism of glomerulosclerosis
      and progressive renal failure. Transforming growth factor-beta (TGFbeta) is a
      central mediator of signaling networks that control a diverse set of cellular
      processes, such as cell proliferation, differentiation, and apoptosis. Though
      many key events in TGFbeta1 signaling have been documented at cellular and
      molecular level in podocytes, the complete effects of TGFbeta1 on podocyte
      integrity are still elusive. In this study, the function of adhesion protein
      integrin beta1, focal adhesion kinase (FAK), and a small GTPase Ras was explored
      in TGFbeta1-induced podocyte injury. In cultured mouse podocyte, caspase 3
      positive cells were counted by flow cytometry to evaluate podocyte damage at
      different time points after TGFbeta1 treatment. Immunoblotting assay showed that
      integrin beta1, FAK, Src kinase, and an adaptor protein Grb2 were activated
      rapidly after TGFbeta1 stimulation. Active Ras Pull-Down assay revealed that the
      active Ras (GTP-bound Ras) level was upregulated in TGFbeta1-treated cell.
      Immunoprecipitation results displayed that TGFbeta1 enhanced the complex
      formation of integrin beta1, FAK and Src kinase, as well as FAK, Grb2 and Ras.
      The FAK inhibitor TAE226 and the specific knockdown of Grb2 remarkably alleviated
      TGFbeta1-induced podocyte apoptosis. The activation of p38MAPK and Erk1/2, and
      the nuclear translocation of NFkappaB(p65) were increased evidently in TGFbeta1
      treated cell, which could be dramatically prohibited by the application of the
      p38MAPK inhibitor SB202190 and the Ras inhibitor FPT Inhibitor III. The Src
      kinase inhibitor PP2 obviously prevented the activation of FAK and Ras, as well
      as the translocation of NFkappaB(p65) from cytoplasm to nuclei. The PP2, FPT
      Inhibitor III, and SB202190 significantly decreased TGFbeta1-induced podocyte
      apoptosis. Taken together, these data demonstrated that the activation of
      integrin beta1/Src/FAK and Grb2/RasGTP should be responsible for TGFbeta1-induced
      podocyte damage through the p38MAPK and Erk1/2-mediated nuclear translocation of
      NFkappaB(p65). 

PMID- 24036213
TI  - Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated BST
      2/tetherin regulation.
AB  - BST-2 is a virus restriction factor whose expression is principally induced by
      IFNalpha through the type I IFN receptor. However, expression of BST-2 is
      modulated by mitogens, notably the TLR4 agonist - LPS, via mechanisms that are
      poorly understood. In this study, the role of TLR4 pathway on BST-2 expression
      was examined. We demonstrate that the TLR4/PI3K signaling pathway regulates both
      constitutive and LPS-induced BST-2 expression. LPS stimulation induces BST-2
      expression in a manner dependent on TLR4/TRIF/IRF3 pathway. Genetic deletion or
      pharmacological inhibition of signaling through TLR4, as well as, the deletion of
      the TRIF and IRF3 genes blunts BST-2 induction by LPS. However, MYD88-/- cells
      have enhanced BST-2 levels and respond to LPS-mediated induction of BST-2. High
      level of BST-2 in MYD88 null cells is dependent on IFNbeta since antibody
      mediated neutralization of IFNbeta synthesis results in reduced BST-2 levels in
      these cells. Similar to the effect of MYD88, inhibition of PI3K activity elevates
      basal BST-2 level and augments LPS-induced BST-2 expression. Importantly, BST-2
      regulation via TLR4 and PI3K is transcriptionally controlled. We discovered that
      actinomycin D-mediated blocking of gene transcription and inhibition of protein
      synthesis with cycloheximide result in impairment of BST-2 mRNA expression. Taken
      together, our results demonstrate that activation of TLR4 results in TRIF/IRF3
      mediated positive regulation of BST-2 or MYD88/PI3K-directed negative regulation
      of BST-2. Thus, our findings enlist BST-2 as one of the genes regulated by PI3K
      downstream of TLR4 and identify the TLR4/PI3K signaling as a novel pathway that
      controls BST-2 expression. 

PMID- 24036211
TI  - HER2/HER3 regulates extracellular acidification and cell migration through MTK1
      (MEKK4).
AB  - Human MAP3K4 (MTK1) functions upstream of mitogen activated protein kinases
      (MAPKs). In this study we show MTK1 is required for human epidermal growth factor
      receptor 2/3 (HER2/HER3)-heregulin beta1 (HRG) induced cell migration in MCF-7
      breast cancer cells. We demonstrate that HRG stimulation leads to association of
      MTK1 with activated HER3 in MCF-7 and T-47D breast cancer cells. Activated HER3
      association with MTK1 is dependent on HER2 activation and is decreased by pre
      treatment with the HER2 inhibitor, lapatinib. Moreover, we also identify the
      actin interacting region (AIR) on MTK1. Disruption of actin cytoskeletal
      polymerization with cytochalasin D inhibited HRG induced MTK1/HER3 association.
      Additionally, HRG stimulation leads to extracellular acidification that is
      independent of cellular proliferation. HRG induced extracellular acidification is
      significantly inhibited when MTK1 is knocked down in MCF-7 cells. Similarly, pre
      treatment with lapatinib significantly decreased HRG induced extracellular
      acidification. Extracellular acidification is linked with cancer cell migration.
      We performed scratch assays that show HRG induced cell migration in MCF-7 cells.
      Knockdown of MTK1 significantly inhibited HRG induced cell migration.
      Furthermore, pre-treatment with lapatinib also significantly decreased cell
      migration. Cell migration is required for cancer cell metastasis, which is the
      major cause of cancer patient mortality. We identify MTK1 in the HER2/HER3-HRG
      mediated extracellular acidification and cell migration pathway in breast cancer
      cells. 

PMID- 24036214
TI  - SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer
      stem-like cells.
AB  - SOX2 is an essential transcription factor for stem cells and plays a role in
      tumorigenesis, however its role in prostate cancer stem cells (PCSCs) remains
      unclear. We report here a significant upregulation of SOX2 at both mRNA and
      protein levels in DU145 PCSCs propagated as suspension spheres in vitro. The
      expression of SOX2 in DU145 PCSCs is positively regulated by epidermal growth
      factor receptor (EGFR) signaling. Activation of EGFR signaling, following the
      addition of epidermal growth factor (EGF) or ectopic expression of a
      constitutively-active EGFR mutant (EGFRvIII), increased SOX2 expression and the
      self-renewal of DU145 PCSCs. Conversely, a small molecule EGFR inhibitor (AG1478)
      blocked EGFR activation, reduced SOX2 expression and inhibited PCSC self-renewal
      activity, implicating SOX2 in mediating EGFR-dependent self-renewal of PCSCs. In
      line with this notion, ectopic SOX2 expression enhanced EGF-induced self-renewal
      of DU145 PCSCs, while SOX2 knockdown reduced PCSC self-renewal with EGF treatment
      no longer capable of enhancing their propagation. Furthermore, SOX2 knockdown
      reduced the capacity of DU145 PCSCs to grow under anchorage-independent
      conditions. Finally, DU145 PCSCs generated xenograft tumors more aggressively
      with elevated levels of SOX2 expression compared to xenograft tumors derived from
      non-PCSCs. Collectively, we provide evidence that SOX2 plays a critical role in
      EGFR-mediated self-renewal of DU145 PCSCs. 

PMID- 24036215
TI  - Ras activation mediates WISP-1-induced increases in cell motility and matrix
      metalloproteinase expression in human osteosarcoma.
AB  - WISP-1 is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov)
      family of matrix cellular proteins. Osteosarcoma is a type of highly malignant
      tumor with a potent capacity to invade locally and cause distant metastasis.
      However, the effect of WISP-1 on migration activity in human osteosarcoma cells
      is mostly unknown. In this study, we first found that the expression of WISP-1 in
      osteosarcoma patients was significantly higher than that in normal bone and
      corrected with tumor stage. Exogenous treatment of osteosarcoma cells with WISP-1
      promoted cell motility and matrix metalloproteinase (MMP)-2 and MMP-9 expression.
      In addition, the Ras and Raf-1 inhibitor or siRNA abolished WISP-1-induced cell
      migration and MMP expression. On the other hand, activation of the Ras, Raf-1,
      MEK, ERK, and NF-kappaB signaling pathway after WISP-1 treatment was
      demonstrated, and WISP-1-induced expression of MMPs and migration activity were
      inhibited by the specific inhibitor, and mutant of MEK, ERK, and NF-kappaB
      cascades. Taken together, our results indicated that WISP-1 enhances the
      migration of osteosarcoma cells by increasing MMP-2 and MMP-9 expression through
      the integrin receptor, Ras, Raf-1, MEK, ERK, and NF-kappaB signal transduction
      pathway. 

PMID- 24036216
TI  - 5-Lipoxygenase contributes to PPARgamma activation in macrophages in response to
      apoptotic cells.
AB  - Macrophage polarization to an anti-inflammatory phenotype upon contact with
      apoptotic cells is a contributing hallmark to immune suppression during the late
      phase of sepsis. Although the peroxisome proliferator-activated receptor gamma
      (PPARgamma) supports this macrophage phenotype switch, it remains elusive how
      apoptotic cells activate PPARgamma. Assuming that a molecule causing PPARgamma
      activation in macrophages originates in the cell membrane of apoptotic cells we
      analyzed lipid rafts from apoptotic, necrotic, and living human Jurkat T cells
      which showed the presence of 5-lipoxygenase (5-LO) in lipid rafts of apoptotic
      cells only. Incubating macrophages with lipid rafts of apoptotic, but not
      necrotic or living cells, induced PPAR responsive element (PPRE)-driven mRuby
      reporter gene expression in RAW 264.7 macrophages stably transduced with a 4xPPRE
      containing vector. Experiments with lipid rafts of apoptotic murine EL4 T cells
      revealed similar results. To verify the involvement of 5-LO in activating
      PPARgamma in macrophages, Jurkat T cells were incubated with the 5-LO inhibitor
      MK-866 prior to induction of apoptosis, which failed to induce mRuby expression.
      Similar results were obtained with lipid rafts of apoptotic EL4 T cells
      preexposed to the 5-LO inhibitors zileuton and CJ-13610. Interestingly, Jurkat T
      cells overexpressing 5-LO failed to activate PPARgamma in macrophages, while
      their 5-LO overexpressing apoptotic counterparts did. Our results suggest that
      during apoptosis 5-LO gets associated with lipid rafts and synthesizes ligands
      that in turn stimulate PPARgamma in macrophages. 

PMID- 24036217
TI  - A nuclear export signal and oxidative stress regulate ShcD subcellular
      localisation: a potential role for ShcD in the nucleus.
AB  - Tumour cells alter their gene expression profile to acquire a more invasive and
      resistant phenotype. Overexpression of the signalling adaptor protein ShcD in
      melanoma was found to be a prerequisite for melanoma migration and invasion. In
      common with other Shc proteins, ShcD has been shown to be involved in coupling
      receptor tyrosine kinases to the Ras-mitogen activated protein kinase signalling
      pathway, and to have a predominant cytoplasmic distribution. Here we report that
      ShcD can exist within the nucleus, and show that its CH2 domain has a critical
      role in nuclear export of ShcD. Analysis of GFP-tagged ShcD mutants containing
      deletions or amino acid substitutions within the CH2 domain revealed
      (83)LCTLIPRM(90) as a functional nuclear export signal. We have further
      demonstrated that ShcD accumulates in the nucleus upon hydrogen peroxide
      treatment in FLAG-ShcD expressing HEK293 cells, as well as 518.A2 melanoma cells.
      Cross linking experiments showed that a proportion of ShcD is associated with
      DNA. Moreover we have shown that ShcD fused to the GAL4 DNA binding domain can
      drive transcription of a GAL4 site-driven luciferase reporter, suggesting a role
      for ShcD in regulating gene transcription. We suggest that ShcD nuclear
      translocation might provide melanoma cells with a mechanism that enables them to
      resist DNA damage due to oxidative stress. 

PMID- 24036218
TI  - Synergism of a natural plant product, oleanolic acid with calcineurin inhibitor
      in prolonging islet allograft survival.
AB  - BACKGROUND: Oleanolic acid (OA) is a natural plant-derived triterpenoid with
      potent anti-inflammatory properties. Since inflammatory cytokines released
      following islet transplantation hinders engraftment and long-term function, we
      determined the synergistic ability of OA to with Cyclosporine-A (CSA), a
      calcineurin inhibitor in improving islet allograft's function and survival.
      METHODS: C57BL/6 mice were rendered diabetic using streptozotocin (200mg/kg).
      BALB/c islets were transplanted under the kidney capsule alone (control) or along
      with administration of OA alone, CSA alone or a combination of both OA and CSA
      (OA+CSA). T-cell infiltration was analyzed by immunohistochemistry; cytokine
      concentration was analyzed by Luminex; T-cell cytokine phenotype was analyzed by
      ELISpot; and alloimmune response was analyzed by flow cytometry. RESULTS: OA+CSA
      markedly prolonged islet allograft survival compared to controls (37 +/- 5 days
      vs. 8 +/- 3 days). A significant decrease of CD4+ (34 +/- 9 vs. 154 +/- 42
      cells/hpf) and CD8+ T-cellular (46 +/- 22 vs. 224 +/- 51 cells/hpf, p<0.0001)
      infiltration into the graft in OA+CSA treated mice compared to controls. A
      significant decrease in T cell infiltration was demonstrated in the OA+CSA cohort
      over either compound application individually. An increase in anti-inflammatory
      molecules, IL-10 (2.4-fold) and vascular endothelial growth factor (1.6-fold),
      along with decreased pro-inflammatory cytokines IFN-gamma, IL-1beta (1.3-2.4
      fold) and IL-17 (3.2-fold) was demonstrated. OA+CSA also significantly decreased
      the frequency of allo-specific T-cell responses. Development of antibodies
      against donor antigens was also delayed (39 vs 22 days; p<0.05) in the OA+CSA
      cohort over administration of either agent individually. CONCLUSIONS: OA and CSA
      exert synergistic effect towards enhancing islet allograft survival and function.
      This synergistic effect resulted in markedly reduced graft infiltrating cells
      with attenuation of inflammatory cytokine milieu leading to impairment of both
      cellular and humoral alloimmune responses. Therefore, novel therapeutic
      approaches involving combination of OA with calcineurin-inhibitor based
      immunosuppressant CSA will produce potential beneficial outcomes in clinical
      islet transplantation.

PMID- 24036219
TI  - Neural network integration of field observations for soil endocrine disruptor
      characterisation.
AB  - A neural network approach was used to predict the presence and concentration of a
      range of endocrine disrupting compounds (EDCs), based on field observations. Soil
      sample concentrations of endocrine disrupting compounds (EDCs) and site
      environmental characteristics, drawn from the National Soil Inventory of Scotland
      (NSIS) database, were used. Neural network models were trained to predict soil
      EDC concentrations using field observations for 184 sites. The results showed
      that presence/absence and concentration of several of the EDCs, mostly no longer
      in production, could be predicted with some accuracy. We were able to predict
      concentrations of seven of 31 compounds with r(2) values greater than 0.25 for
      log-normalised values and of eight with log-normalised predictions converted to a
      linear scale. Additional statistical analyses were carried out, including Root
      Mean Square Error (RMSE), Mean Error (ME), Willmott's index of agreement, Percent
      Bias (PBIAS) and ratio of root mean square to standard deviation (RSR). These
      analyses allowed us to demonstrate that the neural network models were making
      meaningful predictions of EDC concentration. We identified the main predictive
      input parameters in each case, based on a sensitivity analysis of the trained
      neural network model. We also demonstrated the capacity of the method for
      predicting the presence and level of EDC concentration in the field, identified
      further developments required to make this process as rapid and operator-friendly
      as possible and discussed the potential value of a system for field surveys of
      soil composition. 

PMID- 24036220
TI  - Ecological deficit and use of natural capital in Luxembourg from 1995 to 2009.
AB  - Scarcity of natural resources and productive land is a global issue affecting the
      provision of goods and services at the country scale. This is particularly true
      for small regions with highly developed economies such as Luxembourg, which
      usually balance the chronic unavailability of resources (in particular with
      regard to fossil fuels) with an increasing demand of imported raw materials,
      energy and manufactured commodities. Based on historical time-series analysis
      (from 1995 to 2009), this paper determines the state of natural capital (NC)
      utilization in Luxembourg and estimates its ecological deficit (ED). Accordingly,
      solar energy demand (SED) and ecological footprint (EF) for Luxembourg have been
      initially calculated based on a recently developed country-specific
      environmentally extended input-output model. Thereafter, these indicators have
      been compared to the corresponding annual trends of potential NC (estimated using
      the emergy concept) and biocapacity, respectively. Results show that the trends
      in ED and in the use of NC in Luxembourg have not increased substantially during
      the years surveyed. However, the estimates also highlight that the NC of
      Luxembourg is directly and indirectly overused by a factor higher than 20, while
      circa 9 additional 'Luxembourg states' would be ideally necessary to satisfy the
      current land's requirements of the country and thus balance the impact induced by
      the EF. An in-depth analysis of the methodological advantages and limitations
      behind our modelling approach has been performed to validate our findings and
      propose a road map to improve the environmental accounting for NC and biocapacity
      in Luxembourg. 

PMID- 24036221
TI  - Human health and the water environment: using the DPSEEA framework to identify
      the driving forces of disease.
AB  - There is a growing awareness of global forces that threaten human health via the
      water environment. A better understanding of the dynamic between human health and
      the water environment would enable prediction of the significant driving forces
      and effective strategies for coping with or preventing them. This report details
      the use of the Driving Force-Pressure-State-Exposure-Effect-Action (DPSEEA)
      framework to explore the linkage between water-related diseases and their
      significant driving forces. The DPSEEA frameworks indicate that a select group of
      driving forces, including population growth, agriculture, infrastructure (dams
      and irrigation), and climate change, is at the root cause of key global disease
      burdens. Construction of the DPSEEA frameworks also allows for the evaluation of
      public health interventions. Sanitation was found to be a widely applicable and
      effective intervention, targeting the driver/pressure linkage of most of the
      water-related diseases examined. Ultimately, the DPSEEA frameworks offer a
      platform for constituents in both the health and environmental fields to
      collaborate and commit to a common goal targeting the same driving forces. 

PMID- 24036222
TI  - Genomic studies on nitrogen metabolism in Halomonas boliviensis: metabolic
      pathway, biochemistry and evolution.
AB  - Halomonas boliviensis LC1(T)=DSM 15516(T) is a halophilic bacterium that
      copiously produces osmolytes and polyesters. The growth of H. boliviensis is
      restricted when glutamate or glutamine is not included in its culture medium. The
      concentration of glutamate in the medium can regulate the production of either
      osmolytes or polyesters. However, genomic studies on the nitrogen assimilation
      have not been performed on H. boliviensis and other members of the family
      Halomonadaceae. Glutamate metabolism in H. boliviensis was discerned based on
      genome sequence analysis. The genome sequences of other Halomonadaceae members
      revealed similar enzymes to those found in H. boliviensis. H. boliviensis and H.
      elongata DSM 2581(T) acquired distinct glutamate dehydrogenase genes through
      horizontal gene transfer from a different bacterium. Two alleles of glutamine
      synthetase could be found in H. boliviensis, one of which was obtained from a
      thermophilic archaeon via horizontal gene transfer. Two subunits of glutamate
      synthase were also present in H. boliviensis. The small beta-subunit had a
      molecular weight of 52 kDa and was phylogenetically closely affiliated to
      proteins of other halomonads and Gammaproteobacteria. The large (161 kDa) alpha
      subunit of the halomonads gathered in a separate phylogenetic group, hence
      glutamate synthase alpha-subunits of halomonads may be included a novel group of
      enzymes. Furthermore, putative enzymes obtained from the genome of H. boliviensis
      should permit complete glutamate metabolism. A similar metabolism should be
      followed by other halomonads. However, some phenotypic differences between
      halomonads, such as the ability to assimilate ammonia, resulted as a consequence
      of horizontal gene transfer. Each enzyme that forms part of the glutamate
      metabolism in prokaryotes evolved following a different pattern. Yet, most
      enzymes of halomonads diverged in phylogenetic clusters composed of
      Proteobacteria, as might be expected.

PMID- 24036223
TI  - New T530C mutation in the aspartoacylase gene caused Canavan disease with no
      correlation between severity and N-acetylaspartate excretion.
AB  - OBJECTIVE: Canavan disease (OMIM 271900) is a severe autosomal recessive
      neurodegenerative disorder characterized by spongy degeneration of the brain and
      caused by mutations in the gene encoding for aspartoacylase (ASPA). The enzyme is
      responsible for the catalyses of the brain-specific compound N-acetylaspartate
      (NAA). DESIGN AND METHODS: We report the case of two Egyptian sibling patients
      suspected of Canavan disease (CD) showing clinical deterioration, white matter
      degeneration, megalencephaly and severe intellectual impairment. The patients
      underwent magnetic resonance imaging (MRI) and biochemical analysis of NAA in
      biological fluid samples (serum and urine). Subsequently, in order to determine
      the mutation responsible for CD in these two sibs, a molecular biological
      examination was performed. RESULTS: MRI findings and quantification of high NAA
      excretion (1378.5 and 680.1MUmolNAA/mmolcreatinine in urine of 4months and 4years
      old patients, respectively) confirmed the diagnosis of CD and prompted a search
      for the responsible mutation. The molecular biological analysis revealed
      homozygosity for the substitution T530C (Ile177Thr) in the exon 4 of the ASPA
      gene in both sibs. A total loss of enzymatic activity was also recorded.
      CONCLUSIONS: The substitution T530C (Ile177Thr) results in a novel missense
      mutation causing a CD phenotype with severe clinical characteristics. This
      mutation was not previously described in the literature. In these two sibs,
      urinary concentration of NAA appears to correlate inversely to symptom severity
      and CD progression.

PMID- 24036224
TI  - A longitudinal study of temperament continuity through IBQ, TBAQ and CBQ.
AB  - The aim of this work was to study the continuity of temperament in a Spanish
      sample (n = 60), covering the developmental stages of infancy, toddlerhood and
      childhood. Temperamental dimensions showed, with few exceptions, as much
      homotypic as heterotypic continuity as was to be expected. At the level of latent
      superconstructs continuity, we found that Anger and Fear followed different
      developmental paths and showed continuity over all the periods evaluated.
      Positive Affect/Regulation superconstruct showed continuity from infancy to
      toddlerhood. From toddlerhood, Positive Affect/Regulation showed continuity with
      the superconstruct of Effortful Control but not with the superconstruct of
      Surgency/Extraversion. At an ipsative level, we found two groups of subjects,
      labeled 'nonexpressive/controlled' and 'noncontrolled/expressive'. Generally,
      these results confirm the stability of temperament in the periods analyzed and
      underline the importance of toddlerhood as a transitional period in the maturity
      of self-regulatory capabilities shown in childhood.

PMID- 24036225
TI  - Ablation of multiwavelet re-entry guided by circuit-density and distribution:
      maximizing the probability of circuit annihilation.
AB  - BACKGROUND: A key mechanism responsible for atrial fibrillation is multiwavelet
      re-entry (MWR). We have previously demonstrated improved efficiency of ablation
      when lesions were placed in regions of high circuit-density. In this study, we
      undertook a quantitative assessment of the relative effect of ablation on the
      probability of MWR termination and the inducibility of MWR, as a function of
      lesion length and circuit-density overlap. METHODS AND RESULTS: We used a
      computational model to simulate MWR in tissues with (and without) localized
      regions of decreased action potential duration and increased intercellular
      resistance. We measured baseline circuit-density and distribution. We then
      assessed the effect of various ablation lesion sets on the inducibility and
      duration of MWR as a function of ablation lesion length and overlap with circuit
      density. Higher circuit-density reproducibly localized to regions of shorter
      wavelength. Ablation lines with high circuit-density overlap showed maximum
      decreases in duration of MWR at lengths equal to the distance from the tissue
      boundary to the far side of the high circuit-density region (high-overlap, -43.5%
      [confidence interval, -22.0% to -65.1%] versus low-overlap, -4.4% [confidence
      interval, 7.3% to -16.0%]). Further ablation (beyond the length required to cross
      the high circuit-density region) provided minimal further reductions in duration
      and increased inducibility. CONCLUSIONS: Ablation at sites of high circuit
      density most efficiently decreased re-entrant duration while minimally increasing
      inducibility. Ablation lines delivered at sites of low circuit-density minimally
      decreased duration yet increased inducibility of MWR.

PMID- 24036226
TI  - A topological similarity measure for proteins.
AB  - We introduce a new measure for assessing similarity among chemical structures,
      based on well-established computational-topology algorithms. We argue that
      although the method considers geometry, it is more than a mere geometric
      similarity measure, as it takes into account, on different geometric scales, the
      important topological features of the compared structures. We prove that our
      measure is rigorous and complies with the proper mathematical requirements. We
      validate the method through comparing different configurations of simple zinc
      finger proteins and present an application on ligands binding to membrane
      proteINS extracted from the Directory of Useful Decoys: Enhanced database and
      corresponding decoys. This article is part of a Special Issue entitled: Viral
      membrane proteins - Channels for cellular networking. 

PMID- 24036227
TI  - NMR-based approach to measure the free energy of transmembrane helix-helix
      interactions.
AB  - Knowledge of the energetic parameters of transmembrane helix-helix interactions
      is necessary for the establishment of a structure-energy relationship for alpha
      helical membrane domains. A number of techniques have been developed to measure
      the free energies of dimerization and oligomerization of transmembrane alpha
      helices, and all of these have their advantages and drawbacks. In this study we
      propose a methodology to determine the magnitudes of the free energy of
      interactions between transmembrane helices in detergent micelles. The suggested
      approach employs solution nuclear magnetic resonance (NMR) spectroscopy to
      determine the population of the oligomeric states of the transmembrane domains
      and introduces a new formalism to describe the oligomerization equilibrium, which
      is based on the assumption that both the dimerization of the transmembrane
      domains and the dissociation of the dimer can occur only upon the collision of
      detergent micelles. The technique has three major advantages compared with other
      existing approaches: it may be used to analyze both weak and relatively strong
      dimerization/oligomerization processes, it works well for the analysis of complex
      equilibria, e.g. when monomer, dimer and high-order oligomer populations are
      simultaneously present in the solution, and it can simultaneously yield both
      structural and energetic characteristics of the helix-helix interaction under
      study. The proposed methodology was applied to investigate the oligomerization
      process of transmembrane domains of fibroblast growth factor receptor 3 (FGFR3)
      and vascular endothelium growth factor receptor 2 (VEGFR2), and allowed the
      measurement of the free energy of dimerization of both of these objects. In
      addition the proposed method was able to describe the multi-state oligomerization
      process of the VEGFR2 transmembrane domain. 

PMID- 24036229
TI  - Concurrent porcine circovirus type 2a (PCV2a) or PCV2b infection increases the
      rate of amino acid mutations of porcine reproductive and respiratory syndrome
      virus (PRRSV) during serial passages in pigs.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) has a high degree of
      genetic and antigenic variability. The purpose of this study was to determine if
      porcine circovirus type 2 (PCV2) infection increases genetic variability of PRRSV
      during serial passages in pigs and to determine if there is a difference in the
      PRRSV mutation rate between pigs concurrently infected with PCV2a or PCV2b. After
      8 consecutive passages of PRRSV alone (group 1), PRRSV with PCV2a (group 2), or
      PCV2b (group 3) in pigs, the sequences of PRRSV structural genes for open reading
      frame (ORF) 5, ORF6, ORF7 and the partial non-structural protein gene (Nsp) 2
      were determined. The total number of identified amino acid mutations in ORF5,
      ORF6, ORF7 and Nsp2 sequences was 30 for PRRSV infection only, 63 for PRRSV/PCV2a
      concurrent infection, and 77 for PRRSV/PCV2b concurrent infection when compared
      with the original VR2385 virus used to infect the passage 1 pigs. Compared to
      what occurred in pigs infected with PRRSV only, the mutation rates in ORF5 and
      ORF6 were significantly higher for concurrent PRRSV/PCV2b infected pigs. The
      PRRSV/PCV2a pigs had a significantly higher mutation rate in ORF7. The results
      from this study indicated that, besides ORF5 and Nsp2, the PRRSV structural genes
      ORF6 and ORF7 were shown to mutate at various degrees when the PRRSV was passaged
      over time in vivo. Furthermore, a significantly higher mutation rate of PRRSV was
      observed when pigs were co-infected with PCV2 highlighting the importance of
      concurrent infections on PRRSV evolution and control. 

PMID- 24036228
TI  - Mutations in the feline immunodeficiency virus envelope glycoprotein confer
      resistance to a dominant-negative fragment of Tsg101 by enhancing infectivity and
      cell-to-cell virus transmission.
AB  - The Pro-Ser-Ala-Pro (PSAP) motif in the p2 domain of feline immunodeficiency
      virus (FIV) Gag is required for efficient virus release, virus replication, and
      Gag binding to the ubiquitin-E2-variant (UEV) domain of Tsg101. As a result of
      this direct interaction, expression of an N-terminal fragment of Tsg101
      containing the UEV domain (referred to as TSG-5') inhibits FIV release. In these
      respects, the FIV p2(Gag) PSAP motif is analogous to the PTAP motif of HIV-1
      p6(Gag). To evaluate the feasibility of a late domain-targeted inhibition of
      virus replication, we created an enriched Crandell-Rees feline kidney (CRFK) cell
      line (T5'(hi)) that stably expresses high levels of TSG-5'. Here we show that
      mutations in either the V3 loop or the second heptad repeat (HR2) domain of the
      FIV envelope glycoprotein (Env) rescue FIV replication in T5'(hi) cells without
      increasing FIV release efficiency. TSG-5'-resistance mutations in Env enhance
      virion infectivity and the cell-cell spread of FIV when diffusion is limited
      using a semi-solid growth medium. These findings show that mutations in
      functional domains of Env confer TSG-5'-resistance, which we propose enhances
      specific infectivity and the cell-cell transmission of virus to counteract
      inefficient virus release. This article is part of a Special Issue entitled:
      Viral Membrane Proteins-Channels for Cellular Networking. 

PMID- 24036230
TI  - Mosaicism of HTLV-1 5' LTR CpG methylation in the absence of malignancy.
AB  - Viral expression varies widely between untransformed HTLV-1 positive clones
      derived from infected individuals without malignancy. Here we show that, in the
      absence of malignancy, 68% of HTLV-1 positive clones carry deleted (10%) or
      methylated (58%) 5' LTR. These changes were found to contribute to the
      fluctuation of viral expression between clones. 5' LTR deletions strongly
      impaired tax expression and thereby clonal expansion, telomere homeostasis, and
      genetic instability. The effects of CpG methylation on viral transcription were
      qualitatively and quantitatively different from those of LTR deletions and
      preserved the preleukemic features of HTLV-1(+)CD4(+) clones. 5' LTR methylation
      varied not only between clones but also between cells belonging to the same
      clones, between distinct integrated sequences within the same cells, and between
      CpG dyads along the 5' LTR. Such distributions suggest that a dynamic methylation
      spectrum might help sustain persistent infection. 

PMID- 24036232
TI  - Antisense therapy for hepatitis C virus infection.

PMID- 24036233
TI  - Purification and molecular structure of digalactosyl myo-inositol (DGMI),
      trigalactosyl myo-inositol (TGMI), and fagopyritol B3 from common buckwheat seeds
      by NMR.
AB  - Three galactosyl cyclitols, digalactosyl myo-inositol (assigned the trivial name
      DGMI), trigalactosyl myo-inositol (assigned the trivial name TGMI), and
      trigalactosyl d-chiro-inositol (fagopyritol B3), were isolated from common
      buckwheat (Fagopyrum esculentum Moench) seeds. Structures of the three compounds
      were determined by 2D NMR spectroscopy. DGMI is alpha-d-galactopyranosyl-(1->6)
      alpha-d-galactopyranosyl-(1->1)-1l-myo-inositol, TGMI is alpha-d-galactopyranosyl
      (1->6)-alpha-d-galactopyranosyl-(1->6)-alpha-d-galactopyranosyl-(1->1)-1l-myo
      inositol, and fagopyritol B3 is alpha-d-galactopyranosyl-(1->6)-alpha-d
      galactopyranosyl-(1->6)-alpha-d-galactopyranosyl-(1->2)-1d-chiro-inositol. DGMI
      and TGMI are higher oligomers of galactinol, a major galactosyl donor in plant
      seeds. Fagopyritol B3 is a higher oligomer of the fagopyritol B series and one of
      six fagopyritols found in buckwheat seeds and in the bran milling fraction.
      Samples of TGMI and fagopyritol B3 also contained the compounds N-(beta
      glucopyranosyl)-nicotinic acid and beta-d-apiofuranosyl-(1->6)-beta-d-(1-O
      methyl)-glucopyranoside. 

PMID- 24036234
TI  - Long-term renal function outcomes after radical cystectomy.
AB  - PURPOSE: We evaluated the long-term natural history of renal function after
      radical cystectomy with urinary diversion and determined factors associated with
      decreased renal function. MATERIALS AND METHODS: We reviewed the records of 1,631
      patients who underwent radical cystectomy between 1980 and 2006. The estimated
      glomerular filtration rate was calculated preoperatively and at various intervals
      after surgery. A renal function decrease was defined as a greater than 10 ml per
      minute/1.73 m(2) reduction in the estimated glomerular filtration rate.
      Multivariate analysis was done to evaluate the association of clinicopathological
      features, incontinent vs continent diversion type and postoperative complications
      with decreased renal function. RESULTS: A total of 1,241 patients (76%) underwent
      incontinent diversion and 390 (24%) underwent continent diversion. Median
      followup after radical cystectomy in patients alive at last followup was 10.5
      years (IQR 7.1, 15.3). The median preoperative estimated glomerular filtration
      rate was higher in the continent diversion cohort (67 vs 59 ml per minute/1.73
      m(2), p <0.0001). This difference was maintained until 7 years postoperatively,
      after which no difference was noted in renal function by diversion type. By 10
      years after radical cystectomy the risk of a renal function decrease was similar
      for incontinent and continent diversion (71% and 74%, respectively, p = 0.13). On
      multivariate analysis risk factors associated with decreased renal function
      included age (HR 1.03, p <0.0001), preoperative estimated glomerular filtration
      rate (HR 1.05, p <0.0001), chronic hypertension (HR 1.2, p = 0.01), postoperative
      hydronephrosis (HR 1.2, p = 0.03), pyelonephritis (HR 1.3, p = 0.01) and
      ureteroenteric stricture (HR 1.6, p <0.0001). CONCLUSIONS: Decreased renal
      function is noted in most patients during long-term followup after radical
      cystectomy. Postoperative hydronephrosis, pyelonephritis and ureteroenteric
      stricture represent potentially modifiable factors associated with a decrease.
      Choice of urinary diversion was not independently associated with decreased renal
      function.

PMID- 24036235
TI  - Impact of preoperative anemia on oncologic outcomes of upper tract urothelial
      carcinoma treated with radical nephroureterectomy.
AB  - PURPOSE: We evaluated the impact of preoperative anemia on oncologic outcomes in
      patients with upper tract urothelial carcinoma treated with radical
      nephroureterectomy. MATERIALS AND METHODS: A total of 282 patients with upper
      tract urothelial carcinoma underwent radical nephroureterectomy. Preoperatively
      measured hemoglobin values were stratified into normal and anemia based on the
      WHO classification of 13 gm/dl or less and 12 or less considered anemia in males
      and females, respectively. We performed sensitivity analysis based on
      contemporary anemia classifications adjusted for the impact of age, gender and
      race with anemia considered a hemoglobin value of 13.7 gm/dl or less and 13.2 or
      less in white males younger than 60 and 60 years old or older, respectively, and
      12.2 gm/dl or less in white females of all ages. Univariable and multivariable
      Cox regression analyses were done to assess the effects of anemia on oncologic
      outcomes. RESULTS: Median preoperative hemoglobin was 13.2 gm/dl (IQR 11.7,
      14.3). A total of 112 patients (39.7%) were anemic by the WHO classification vs
      129 (45.7%) by the contemporary classification. Anemia was associated with lymph
      node metastasis, lymphovascular invasion, sessile tumor architecture, tumor
      necrosis, advanced age and a higher ECOG (Eastern Cooperative Oncology Group)
      performance score using the WHO and/or the contemporary definition (p <=0.044).
      At a median 30-month followup anemia was associated with decreased recurrence
      free (p <=0.008) and cancer specific (p <0.001) survival on Kaplan-Meier
      analyses. On multivariable analysis adjusted for standard clinicopathological
      factors anemia remained an independent predictor of disease recurrence (HR 1.76,
      95% CI 1.17-2.63 and 1.89, 95% CI 1.26-2.86) and cancer specific mortality (HR
      1.88, 95% CI 1.15-3.08 and 2.04, 95% CI 1.21-3.45) by the WHO and contemporary
      classifications, respectively. CONCLUSIONS: Preoperative anemia is an independent
      predictor of disease recurrence and cancer specific mortality. It is associated
      with aggressive tumor features in patients with upper tract urothelial carcinoma
      treated with radical nephroureterectomy. Hemoglobin is a promising marker for
      patient counseling and risk stratification for additional treatment decision
      making.

PMID- 24036231
TI  - A review of quality of life after predictive testing for and earlier
      identification of neurodegenerative diseases.
AB  - The past decade has witnessed an explosion of evidence suggesting that many
      neurodegenerative diseases can be detected years, if not decades, earlier than
      previously thought. To date, these scientific advances have not provoked any
      parallel translational or clinical improvements. There is an urgency to
      capitalize on this momentum so earlier detection of disease can be more readily
      translated into improved health-related quality of life for families at risk for,
      or suffering with, neurodegenerative diseases. In this review, we discuss health
      related quality of life (HRQOL) measurement in neurodegenerative diseases and the
      importance of these "patient reported outcomes" for all clinical research. Next,
      we address HRQOL following early identification or predictive genetic testing in
      some neurodegenerative diseases: Huntington disease, Alzheimer's disease,
      Parkinson's disease, Dementia with Lewy bodies, frontotemporal dementia,
      amyotrophic lateral sclerosis, prion diseases, hereditary ataxias, Dentatorubral
      pallidoluysian atrophy and Wilson's disease. After a brief report of available
      direct-to-consumer genetic tests, we address the juxtaposition of earlier disease
      identification with assumed reluctance toward predictive genetic testing. Forty
      one studies examining health-related outcomes following predictive genetic
      testing for neurodegenerative disease suggested that (a) extreme or catastrophic
      outcomes are rare; (b) consequences commonly include transiently increased
      anxiety and/or depression; (c) most participants report no regret; (d) many
      persons report extensive benefits to receiving genetic information; and (e)
      stigmatization and discrimination for genetic diseases are poorly understood and
      policy and laws are needed. Caution is appropriate for earlier identification of
      neurodegenerative diseases but findings suggest further progress is safe,
      feasible and likely to advance clinical care. 

PMID- 24036236
TI  - Locoregional small cell carcinoma of the bladder: clinical characteristics and
      treatment patterns.
AB  - PURPOSE: Because small cell carcinoma of the bladder is a relatively rare tumor
      type, literature about its treatment remains limited. We determined patterns of
      care and survival after treatment in what is to our knowledge the largest series
      to date of patients with locoregional small cell carcinoma of the bladder.
      MATERIALS AND METHODS: We identified patients with localized/locally advanced
      (cTis-cT4, cN0 or cM0) bladder small cell carcinoma diagnosed between 1998 and
      2010 from the National Cancer Database (NCDB). Treatment was categorized as
      bladder preservation therapy, radical cystectomy alone, bladder preservation
      therapy with multimodal treatment or radical cystectomy plus multimodal
      treatment. We performed Kaplan-Meier overall survival analysis to evaluate
      differential survival between treatment groups. RESULTS: A total of 625 patients
      met study inclusion criteria. Median age at diagnosis was 73 years (range 36 to
      90) and 65% of patients presented with cT2 disease. Patients were treated with
      bladder preservation therapy (174 or 27.8%), bladder preservation therapy plus
      multimodal treatment (333 or 53.3%), radical cystectomy alone (46 or 7.4%) and
      radical cystectomy plus multimodal treatment (72 or 11.5%) with a 3-year overall
      survival rate of 23% (95% CI 15-32), 35% (95% CI 30-45), 38% (95% CI 17-60) and
      30.1% (95% CI 16-47), respectively. Overall survival was most favorable for
      radical cystectomy alone plus neoadjuvant chemotherapy with a 3-year rate of 53%
      (95% CI 19-79). CONCLUSIONS: In the United States locoregional small cell
      carcinoma of the bladder develops predominantly in white males, in whom treatment
      is performed at metropolitan, comprehensive community cancer centers. Most
      patients were treated with bladder preservation therapy and most received
      multimodal therapy. Patients who received neoadjuvant chemotherapy followed by
      radical cystectomy had the most favorable survival.

PMID- 24036237
TI  - Therapeutic effects of IGF-1 on stress urinary incontinence in rats with
      simulated childbirth trauma.
AB  - PURPOSE: We examined the effect of IGF-1 in a rat model of stress urinary
      incontinence induced by simulated childbirth trauma. MATERIALS AND METHODS:
      Simulated birth trauma was induced by vaginal distension in female Sprague
      Dawley(r) rats. Four, 7, 14 and 28 days after distension we performed functional
      assessment by measuring leak point pressure, urethral baseline pressure and the
      urethral response during a passive increment in intravesical pressure. The
      expression of IGF-1 and IGF1R mRNA and protein in damaged tissues was examined by
      real-time reverse transcriptase-polymerase chain reaction and
      immunohistochemistry. Thereafter hrIGF-1 (50 and 150 MUg/kg per day) was
      continuously delivered from 1 day before distension using subcutaneous osmotic
      pumps. Four and 7 days after distension the effect of hrIGF-1 treatment was
      examined by functional analysis of leak point pressure, urethral baseline
      pressure and the urethral response as well as Western blot and histological
      analysis. RESULTS: After 4 and 7 days rats with vaginal distension had
      significantly decreased leak point pressure, urethral baseline pressure and
      urethral responses. IGF-1 and IGF1R mRNA and protein levels were significantly
      increased in urethral and pudendal nerves 4 and 7 days after distension. IGF-1
      treated groups showed significant improvement in leak point pressure, urethral
      baseline pressure and urethral responses 4 and 7 days after distension. Moreover,
      IGF-1 treatment increased Akt phosphorylation and induced cellular proliferation
      and antiapoptotic effects in the urethra. CONCLUSIONS: IGF-1 treatment
      accelerated recovery from stress urinary incontinence induced by simulated
      childbirth trauma in association with activation of the Akt signal transduction
      pathway in rats. This suggests that IGF-1 has therapeutic potential for stress
      urinary incontinence in women.

PMID- 24036238
TI  - A three-dimensional co-culture model of the aortic valve using magnetic
      levitation.
AB  - The aortic valve consists of valvular interstitial cells (VICs) and endothelial
      cells (VECs). While these cells are understood to work synergistically to
      maintain leaflet structure and valvular function, few co-culture models of these
      cell types exist. In this study, aortic valve co-cultures (AVCCs) were assembled
      using magnetic levitation and cultured for 3 days. Immunohistochemistry and
      quantitative reverse-transcriptase polymerase chain reaction were used to assess
      the maintenance of cellular phenotype and function, and the formation of
      extracellular matrix. AVCCs stained positive for CD31 and alpha-smooth muscle
      actin (alphaSMA), demonstrating that the phenotype was maintained. Functional
      markers endothelial nitric oxide synthase (eNOS), von Willebrand factor (VWF) and
      prolyl-4-hydroxylase were present. Extracellular matrix components collagen type
      I, laminin and fibronectin also stained positive, with reduced gene expression of
      these proteins in three dimensions compared to two dimensions. Genes for collagen
      type I, lysyl oxidase and alphaSMA were expressed less in AVCCs than in 2-D
      cultures, indicating that VICs are quiescent. Co-localization of CD31 and
      alphaSMA in the AVCCs suggests that endothelial-mesenchymal transdifferentiation
      might be occurring. Differences in VWF and eNOS in VECs cultured in two and three
      dimensions also suggests that the AVCCs possibly have anti-thrombotic potential.
      Overall, a co-culture model of the aortic valve was designed, and serves as a
      basis for future experiments to understand heart valve biology.

PMID- 24036239
TI  - Bio-predictive tablet disintegration: effect of water diffusivity, fluid flow,
      food composition and test conditions.
AB  - Food intake may delay tablet disintegration. Current in vitro methods have little
      predictive potential to account for such effects. The effect of a variety of
      factors on the disintegration of immediate release tablets in the
      gastrointestinal tract has been identified. They include viscosity of the media,
      precipitation of food constituents on the surface of the tablet and reduction of
      water diffusivity in the media as well as changes in the hydrodynamics in the
      surrounding media of the solid dosage form. In order to improve the
      predictability of food affecting the disintegration of a dosage form, tablet
      disintegration in various types of a liquefied meal has been studied under static
      vs. dynamic (agitative) conditions. Viscosity, water diffusivity, osmolality and
      Reynolds numbers for the different media were characterized. A quantitative model
      is introduced which predicts the influence of the Reynolds number in the tablet
      disintegration apparatus on the disintegration time. Viscosity, water diffusivity
      and media flow velocity are shown to be important factors affecting dosage form
      disintegration. The results suggest the necessity of considering these parameters
      when designing a predictive model for simulating the in vivo conditions. Based on
      these experiments and knowledge on in vivo hydrodynamics in the GI tract, it is
      concluded that the disintegration tester under current pharmacopoeial conditions
      is operated in an unphysiological mode and no bioprediction may be derived.
      Recommendations regarding alternative mode of operation are made. 

PMID- 24036240
TI  - Can diaphragm pacing improve gas exchange? Insights from quadriplegic patients.

PMID- 24036241
TI  - Diffusion capacity and BMPR2 mutations in pulmonary arterial hypertension.

PMID- 24036242
TI  - A tale of two settings: the role of the Beijing genotype in the epidemiology of
      multidrug-resistant tuberculosis.

PMID- 24036243
TI  - Pneumococcal disease seasonality: incidence, severity and the role of influenza
      activity.
AB  - We tested whether the effect of influenza activity on invasive pneumococcal
      disease incidence and severity varies between age and comorbidity groups. Weekly
      rates of invasive pneumococcal disease were obtained from the Danish National
      Laboratory Surveillance System (1977-2007). Influenza-like illness data were
      collected from a sentinel surveillance system at the Statens Serum Institut
      (Copenhagen, Denmark). We fitted Poisson regression models for invasive
      pneumococcal disease, with predictors of seasonality, trends and influenza
      activity, and allowed the influenza activity variable to vary by comorbidity
      level and clinical presentation. Influenza activity accounted for 8.4% (95% CI
      4.8-11.9%) and 6.9% (95% CI 5.4-10.2%) of all invasive pneumococcal disease cases
      among those aged 15-39 and >=40 years, respectively, but had no measurable impact
      among children aged <15 years. Influenza activity was associated with significant
      increases in the incidence of invasive pneumococcal pneumonia in both children
      and adults. The association was more pronounced among younger adults without
      comorbidities. Case fatality also varied seasonally among the elderly, and this
      variation might be associated with influenza activity. Pneumococcal incidence and
      the severity of disease varied seasonally and between age groups. The effect of
      influenza activity on pneumococcal disease varied between children and adults,
      and this difference was largely due to differences in disease presentation. 

PMID- 24036244
TI  - Prediction of new-onset asthma and nasal allergy by skin prick test and RAST in a
      cohort of adults.
AB  - Limited information exists regarding the incidence and predictors of asthma and
      nasal allergy in adulthood. We determined the incidence rate of asthma and nasal
      allergy in adults and assessed the predictive value of skin prick tests (SPTs)
      and radioallergosorbent tests (RASTs) for these two outcomes. Two German centres
      involved in the European Community Respiratory Health Survey conducted a follow
      up assessment in 2012 of the baseline participants (1185 adults aged 21-47 years
      assessed in 1990). The predictive value of SPTs and RASTs on new-onset asthma and
      nasal allergy was assessed by Cox regression and by calculating the positive or
      negative predictive value. During the 20 years between baseline and follow-up,
      3.1 and 4.4 per 1000 person-years of new-onset asthma and nasal allergy cases
      were recorded, respectively. The hazard ratios for SPTs of any specific and of
      all aeroallergens combined were slightly higher than those of RASTs for asthma
      and nasal allergy. The negative predictive values of both the SPT and RAST were
      very high and similar (0.94-0.96), whereas the postive predictive values were low
      (0.09-0.20). Positive SPT results showed a better association with new onset
      asthma and nasal allergy than positive RAST either to any specific aeroallergens
      or to all combined. 

PMID- 24036245
TI  - Lipid mediator profiles differ between lung compartments in asthmatic and healthy
      humans.
AB  - Oxylipins are oxidised fatty acids that can exert lipid mediator functions in
      inflammation, and several oxylipins derived from arachidonic acid are linked to
      asthma. This study quantified oxylipin profiles in different regions of the lung
      to obtain a broad-scale characterisation of the allergic asthmatic inflammation
      in relation to healthy individuals. Bronchoalveolar lavage fluid (BALF),
      bronchial wash fluid and endobronchial mucosal biopsies were collected from 16
      healthy and 16 mildly allergic asthmatic individuals. Inflammatory cell counts,
      immunohistochemical staining and oxylipin profiling were performed. Univariate
      and multivariate statistics were employed to evaluate compartment-dependent and
      diagnosis-dependent oxylipin profiles in relation to other measured parameters.
      Multivariate modelling showed significantly different bronchial wash fluid and
      BALF oxylipin profiles in both groups (R(2)Y[cum]=0.822 and Q(2)[cum]=0.759).
      Total oxylipin concentrations and five individual oxylipins, primarily from the
      lipoxygenase (LOX) pathway of arachidonic and linoleic acid, were elevated in
      bronchial wash fluid from asthmatics compared to that from healthy controls,
      supported by immunohistochemical staining of 15-LOX-1 in the bronchial
      epithelium. No difference between the groups was found among BALF oxylipins. In
      conclusion, bronchial wash fluid and BALF contain distinct oxylipin profiles,
      which may have ramifications for the study of respiratory diseases. Specific
      protocols for sampling proximal and distal airways separately should be employed
      for lipid mediator studies. 

PMID- 24036246
TI  - Randomised controlled trial of azithromycin in smokers with asthma.

PMID- 24036248
TI  - Purification of antibodies by precipitating impurities using Polyethylene Glycol
      to enable a two chromatography step process.
AB  - The purification of antibodies by precipitating impurities using Polyethylene
      Glycol (PEG) was assessed with the objective of developing a two chromatography
      column purification process. A PEG precipitation method was evaluated for use in
      the industrial purification of recombinant monoclonal antibodies (MAbs).
      Effective and robust precipitation conditions including PEG concentration, pH,
      temperature, time, and protein concentration were identified for several
      different MAbs. A recovery process using two chromatography steps in combination
      with PEG precipitation gave acceptable yield and purity levels for IgG1 and IgG4
      antibodies with a broad range of isoelectric points (pI). PEG precipitation
      removed host cell proteins (HCPs), high molecular weight species (HMWS), leached
      Protein A ligand, and host cell DNA to acceptable levels when run under
      appropriate conditions, and some endogenous virus removal was achieved. 

PMID- 24036249
TI  - Retrocyte Display(r) technology: generation and screening of a high diversity
      cellular antibody library.
AB  - Over the last nearly three decades in vitro display technologies have played an
      important role in the discovery and optimization of antibodies and other proteins
      for therapeutic applications. Here we describe the use of retroviral expression
      technology for the display of full-length IgG on B lineage cells in vitro with a
      hallmark of a tight and stable genotype to phenotype coupling. We describe the
      creation of a high-diversity (>1.0E09 different heavy- and light-chain
      combinations) cell displayed fully human antibody library from healthy donor
      derived heavy- and light-chain gene libraries, and demonstrate the recovery of
      high affinity target-specific antibodies from this library by staining of cells
      with a labeled target antigen and their magnetic- and flow cytometry-based cell
      sorting. The present technology represents a further evolution in the discovery
      of full-length, fully human antibodies using mammalian display, and is termed
      Retrocyte Display(r) (Retroviral B lymphocyte Display). 

PMID- 24036250
TI  - Use of small molecule inhibitors of the Wnt and Notch signaling pathways during
      Xenopus development.
AB  - Small molecule inhibitors of growth factor signaling pathways are extremely
      convenient reagents for investigation of embryonic development. The chemical may
      be introduced at a precise time, the dose can be altered over a large range and
      the chemical may be removed simply by replacing the medium surrounding the
      embryo. Because small molecule modulators are designed to target conserved
      features of a protein, they are usually effective across species. Ideally the
      chemicals offer remarkable specificity for a particular signaling pathway and
      exhibit negligible off-target effects. In this study we examine the use of small
      molecules to modulate the Wnt and Notch signaling pathways in the Xenopus embryo.
      We find that IWR-1 and XAV939 are effective inhibitors of the canonical Wnt
      signaling pathway while BIO is an excellent activator. For Notch signaling, we
      find that both DAPT and RO4929097 are effective inhibitors, but that RO4929097 is
      the more potent reagent. This report provides researchers with useful working
      concentrations of reagents and a small series of genetic and biological assays
      that may be used to characterize the role of Wnt and Notch signaling during
      embryonic development. 

PMID- 24036251
TI  - VEGFR-3 neutralization inhibits ovarian lymphangiogenesis, follicle maturation,
      and murine pregnancy.
AB  - Lymphatic vessels surround follicles within the ovary, but their roles in
      folliculogenesis and pregnancy, as well as the necessity of lymphangiogenesis in
      follicle maturation and health, are undefined. We used systemic delivery of mF4
      31C1, a specific antagonist vascular endothelial growth factor receptor 3 (VEGFR
      3) antibody to block lymphangiogenesis in mice. VEGFR-3 neutralization for 2
      weeks before mating blocked ovarian lymphangiogenesis at all stages of follicle
      maturation, most notably around corpora lutea, without significantly affecting
      follicular blood angiogenesis. The numbers of oocytes ovulated, fertilized, and
      implanted in the uterus were normal in these mice; however, pregnancies were
      unsuccessful because of retarded fetal growth and miscarriage. Fewer patent
      secondary follicles were isolated from treated ovaries, and isolated blastocysts
      exhibited reduced cell densities. Embryos from VEGFR-3-neutralized dams developed
      normally when transferred to untreated surrogates. Conversely, normal embryos
      transferred into mF4-31C1-treated dams led to the same fetal deficiencies
      observed with in situ gestation. Although no significant changes were measured in
      uterine blood or lymphatic vascular densities, VEGFR-3 neutralization reduced
      serum and ovarian estradiol concentrations during gestation. VEGFR-3-mediated
      lymphangiogenesis thus appears to modulate the folliculogenic microenvironment
      and may be necessary for maintenance of hormone levels during pregnancy; both of
      these are novel roles for the lymphatic vasculature. 

PMID- 24036253
TI  - Curcumin improves expression of ghrelin through attenuating oxidative stress in
      gastric tissues of streptozotocin-induced diabetic gastroparesis rats.
AB  - The study was performed to investigate the improved effect of curcumin on
      gastrointestinal function in streptozotocin-induced diabetic rats. Curcumin was
      administrated intragastrically at a dose of 100, 200 and 400 mg/kg/day to
      diabetic rats. After 28 days of treatment, the activity of superoxide dismutase
      (SOD), catalase (CAT), the content of reduced glutathione (GSH) and
      malondialdehyde (MDA) in gastric mucosa was assayed. Furthermore, the gastric
      function was evaluated by hormone secretion and gastric emptying tests. The
      results indicated that: (i) the diabetic rats exhibited significant decreases in
      the above mentioned antioxidative enzymes activities and GSH level and exhibited
      a high level of MDA. After administration of curcumin, the parameters were
      ameliorated to a large extent; (ii) curcumin treatment dose-dependently augmented
      the ghrelin levels of stomach and plasma, which were earlier depleted in the
      diabetic control rats. Conversely, the expression of ghrelin mRNA was decreased
      after curcumin treatment; and (iii) the gastric emptying in curcumin treated
      diabetic rats was notably accelerated compared with the diabetic control rats.
      These findings showed an improved effect of curcumin against streptozotocin
      induced gastroparesis possibly by its antioxidant property.

PMID- 24036254
TI  - Diosmin exhibits anti-hyperlipidemic effects in isoproterenol induced myocardial
      infarcted rats.
AB  - The aim of the present study was to evaluate the protective effects of diosmin on
      experimentally induced myocardial infarcted rats. Diosmin (5 and 10mg/kg body
      weight) was administered orally as pretreatment daily for a period of 10 days.
      Then isoproterenol (100mg/kg) was injected subcutaneously into rats at an
      interval of 24h for 2 days (on 11th and 12th day). Isoproterenol-induced
      myocardial infarcted rats showed significant changes in electrocardiogram and an
      increase in the levels of cardiac markers, compared with normal rats.
      Additionally, increased plasma lipid peroxidation products and altered lipid
      metabolism in the plasma were observed in the isoproterenol-induced myocardial
      infarcted rats. Pretreatment with diosmin (5 and 10mg/kg body weight) minimized
      the electrocardiographic changes, decreased the levels of serum cardiac marker
      enzymes reduced plasma lipid peroxidation and minimized the alterations in the
      lipid metabolism of isoproterenol-induced myocardial infarcted rats. Also,
      diosmin inhibited the enhanced activity of liver HMG CoA reductase. The in vitro
      study revealed the free radical scavenging activity of diosmin. The free radical
      scavenging and anti-hyperlipidaemic effects are the reasons for the
      cardioprotective effects of diosmin. 

PMID- 24036252
TI  - Slug/beta-catenin-dependent proinflammatory phenotype in hypoxic breast cancer
      stem cells.
AB  - Cancer stem cell survival relies on the activation of inflammatory pathways,
      which is speculatively triggered by cell autonomous mechanisms or by
      microenvironmental stimuli. Here, we observed that hypoxic bone marrow stroma
      derived transforming growth factor-beta 1 promotes the growth of human breast
      cancer stem cells as mammospheres. The ensuing Slug-dependent serine 139
      phosphorylation of the DNA damage sensor H2AX in breast cancer stem cells induces
      tumor necrosis factor-alpha and IL-8 mRNAs, whose stability is enhanced by
      cytoplasmic beta-catenin. beta-Catenin also up-regulates and binds miR-221,
      reducing the stability of the miR-221 targets Rad51 and ERalpha mRNAs. Our data
      show that the Slug/beta-catenin-dependent activation of DNA damage signaling
      triggered by the hypoxic microenvironment sustains the proinflammatory phenotype
      of breast cancer stem cells. 

PMID- 24036255
TI  - Investigation of the metabolic effects of chronic clozapine treatment on CCK-1
      receptor deficient Otsuka Long Evans Tokushima Fatty (OLETF) rats.
AB  - Clozapine increases meal size and meal duration, effects similar to the
      pharmacological blockade or congenital deficiency of CCK-1 receptor. We aimed to
      investigate the role of CCK-1 receptor in clozapine-induced weight gain and
      insulin sensitivity in CCK-1 receptor deficient, male Otsuka Long Evans Tokushima
      Fatty rats (OLETF). Long Evans Tokushima Otsuka (LETO) rats served as healthy
      control. Animals were orally treated with either clozapine (10mg/kg) or its
      vehicle over 25 days. Daily metabolic parameters were measured by metabolic
      cages. The insulin sensitivity was determined by hyperinsulinaemic euglycaemic
      glucose clamping (HEGC). Adiposity was determined by measuring the perirenal,
      intraabdominal and epididymal white adipose tissue fat pads. Hypothalamic mRNA
      expression of CCK-1 and CCK-2 receptor was measured by real-time PCR, plasma
      insulin by radioimmunoassay. Clozapine failed to increase weight gain or daily
      food intake, but it increased adiposity, 1st meal size and duration and decreased
      insulin sensitivity both in OLETF or LETO rats. The glucose infusion rate during
      the steady state of the HEGC was unaltered, but the metabolic clearance rate of
      insulin was reduced by the clozapine treatment. Hypothalamic mRNA of CCK-1 and
      CCK-2 receptor was elevated in LETO rats, but the mRNA of CCK-2 receptor was
      reduced by clozapine in OLETF rats. Our results suggest that the CCK-1 receptor
      has no direct role in the clozapine-induced adiposity and insulin resistance. We
      also demonstrated that atypical antipsychotic treatment can induce insulin
      resistance in the absence of manifest obesity in male rats. 

PMID- 24036256
TI  - Protective effect of ischemic preconditioning on ischemia/reperfusion-induced
      acute kidney injury through sympathetic nervous system in rats.
AB  - We have found that a series of brief renal ischemia and reperfusion
      (preconditioning), before the time of ischemia significantly attenuated the
      ischemia/reperfusion-induced acute kidney injury through endothelial nitric oxide
      synthase. In this study, we examined the effects of ischemic preconditioning on
      renal sympathetic nervous system and kidney function in ischemia/reperfusion
      induced acute kidney injury with or without nitric oxide synthase inhibitor.
      Ischemia/reperfusion-induced acute kidney injury was made by clamping the left
      renal artery and vein for 45-min followed by reperfusion, 2 weeks after the
      contralateral nephrectomy. Ischemic preconditioning, consisting of three cycles
      of 2-min ischemia followed by 5-min reperfusion, was performed before the 45-min
      ischemia. Ischemic preconditioning suppressed the enhanced renal sympathetic
      nerve activity during ischemia and the elevated renal venous plasma
      norepinephrine level after reperfusion, and attenuated renal dysfunction and
      histological damage. The renoprotective effect of ischemic preconditioning was
      diminished by N(G)-nitro-L-arginine methyl ester (0.3 mg/kg, i.v.), a
      nonselective nitric oxide synthase inhibitor, 5 min before the start of ischemic
      preconditioning. Thus, ischemic preconditioning decreased renal sympathetic nerve
      activity and norepinephrine release probably through activating nitric oxide
      production, thereby improving ischemia/reperfusion-induced acute kidney injury.

PMID- 24036258
TI  - Effect of dietary alfalfa on the fatty acid composition and indexes of lipid
      metabolism of rabbit meat.
AB  - The objective of the study was to analyse and increase the quality of rabbit meat
      by increasing the levels of natural bioactive compounds through providing fresh
      alfalfa to rabbits as complementary feed. At 50 days of age, forty rabbits were
      divided into two homogeneous groups and fed pelleted feed (control group) or
      pelleted feed plus fresh alfalfa (alfalfa group). The lipid content of meat was
      significantly higher in the control group likely due to the higher feed
      consumption observed in this group. The same trend was observed in the contents
      of myristic, palmitoleic, oleic and linoleic acid. On the contrary, the
      supplementation of fresh alfalfa increased the stearic, linolenic,
      eicosatrienoic, eicosapentaenoic, docosapentaenoic, docosahexaenoic and total
      polyunsaturated fatty acid contents; also the total monounsaturated fatty acids
      and the alpha- and gamma-tocopherol content was significantly lower. Moreover,
      alfalfa ingestion decreased the n-6 content, n-6/n-3 ratio and thrombogenicity
      index.

PMID- 24036257
TI  - Reduction of carrageenan-induced acute pulmonary inflammation in mice by novel
      thiazolidinedione derivative LPSF/RA-4.
AB  - A number of studies have demonstrated the biological activities of peroxisome
      proliferator-activated receptors. However, few studies have addressed the effects
      of the agonists of these receptors on lung diseases. The aim of the present study
      was to evaluate the anti-inflammatory action of a novel synthetic thiazolidine
      derivative (5Z)-3-benzyl-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione
      (LPSF/RA-4) on acute lung inflammation (pleurisy) induced by carrageenan. Forty
      mice were randomly allocated to the following groups: (I) saline control group
      (sham); (II) carrageenan (CAR) group; (III) CAR+LPSF/RA-4 group treated with
      LPSF/RA-4 (60 MUmol/kg); and (IV) INDO group treated with indometacin (5mg/kg).
      Total cell counts and the measure of nitric oxide (NO) were performed in pleural
      exudates. Lung fragments were processed for light microscopy, transmission
      electron microscopy, immunohistochemistry and Western blotting. The influx of
      leucocytes and NO levels were significantly reduced following treatment with
      LPSF/RA-4 and INDO. Histopathological and ultrastructural analyses of the CAR
      group revealed evident tissue alterations, such as oedema, infiltrates of
      inflammatory cells and emphysema. These alterations were significantly reduced in
      the groups treated with LPSF/RA-4 or INDO. Immunohistochemistry revealed an
      increase in inflammatory markers (COX-2, iNOS, TNF-alpha and IL-1beta) in the
      lung tissue of the CAR group, whereas the groups treated with LPSF/RA-4 and INDO
      exhibited significant reductions in such immunomarkers. Western blot analysis
      revealed an increased expression of COX-2 and IL-1 in the CAR group, which was
      reduced by treatment with LPSF/RA-4. The present findings demonstrate the potent
      anti-inflammatory action of the novel derivative thiazolidinedione LPSF/RA-4 in
      acute lung injury induced by carrageenan.

PMID- 24036259
TI  - Physico-chemical and sensory attributes of low-sodium restructured caiman steaks
      containing microbial transglutaminase and salt replacers.
AB  - Our objective was to examine the physico-chemical and sensory attributes of low
      sodium restructured caiman steaks containing microbial transglutaminase (MTG) and
      salt replacers (KCl and MgCl2). Trimmings from caiman carcasses were processed
      into restructured steaks with or without MTG and salt replacers; the five
      treatments were CON (1.5% NaCl), T-1 (1.5% NaCl+1% MTG), T-2 (0.75% NaCl+1%
      MTG+0.75% KCl), T-3 (0.75% NaCl+1% MTG+0.75% MgCl2), and T-4 (0.75% NaCl+1%
      MTG+0.375% KCl+0.375% MgCl2). T-4 demonstrated the greatest (P<0.05) succulence
      and the lowest (P<0.05) values for cooked hardness, springiness, and
      cohesiveness. The greatest (P<0.05) purchase intention was for T-3. Furthermore,
      T-3 and T-4 were similar (P>0.05) to controls in salty flavor. Our findings
      suggest that the combination of MTG, KCl, and MgCl2 can be employed as a suitable
      salt reduction strategy in restructured caiman steaks without compromising
      sensory attributes and consumer acceptance. 

PMID- 24036260
TI  - Tumor growth inhibition through targeting liposomally bound curcumin to tumor
      vasculature.
AB  - Increasing number of Phase I/II clinical studies have demonstrated clinical
      potential of curcumin for treatment of various types of human cancers. Despite
      significant anti-tumor efficacies and bio-safety profiles of curcumin, poor
      systemic bioavailability is retarding its clinical success. Efforts are now being
      directed toward developing stable formulations of curcumin using various drug
      delivery systems. To this end, herein we report on the development of a new tumor
      vasculature targeting liposomal formulation of curcumin containing a lipopeptide
      with RGDK-head group and two stearyl tails, di-oleyolphosphatidylcholine (DOPC)
      and cholesterol. We show that essentially water insoluble curcumin can be
      solubilized in fairly high concentrations (~500 MUg/mL) in such formulation.
      Findings in the Annexin V/Propidium iodide (PI) binding based flow cytometric
      assays showed significant apoptosis inducing properties of the present curcumin
      formulation in both endothelial (HUVEC) and tumor (B16F10) cells. Using syngeneic
      mouse tumor model, we show that growth of solid melanoma tumor can be inhibited
      by targeting such liposomal formulation of curcumin to tumor vasculature. Results
      in immunohistochemical staining of the tumor cryosections are consistent with
      tumor growth inhibition being mediated by apoptosis of tumor endothelial cells.
      Findings in both in vitro and in vivo mechanistic studies are consistent with the
      supposition that the presently described liposomal formulation of curcumin
      inhibits tumor growth by blocking VEGF-induced STAT3 phosphorylation in tumor
      endothelium. To the best of our knowledge, this is the first report on inhibiting
      tumor growth through targeting liposomal formulation of curcumin to tumor
      vasculatures.

PMID- 24036261
TI  - Microbiological quality of ready-to-eat salads: an underestimated vehicle of
      bacteria and clinically relevant antibiotic resistance genes.
AB  - The increase demand for fresh vegetables is causing an expansion of the market
      for minimally processed vegetables along with new recognized food safety
      problems. To gain further insight on this topic we analyzed the microbiological
      quality of Portuguese ready-to-eat salads (RTS) and their role in the spread of
      bacteria carrying acquired antibiotic resistance genes, food products scarcely
      considered in surveillance studies. A total of 50 RTS (7 brands; split or mixed
      leaves, carrot, corn) were collected in 5 national supermarket chains in Porto
      region (2010). They were tested for aerobic mesophilic counts, coliforms and
      Escherichia coli counts as well as for the presence of Salmonella and Listeria
      monocytogenes. Samples were also plated in different selective media with/without
      antibiotics before and after enrichment. The E. coli, other coliforms and
      Enterococcus recovered were characterized for antibiotic resistance profiles and
      clonality with phenotypic and genetic approaches. A high number of RTS presented
      poor microbiological quality (86%--aerobic mesophilic counts, 74%--coliforms, 4%-
      E. coli), despite the absence of screened pathogens. In addition, a high
      diversity of bacteria (species and clones) and antibiotic resistance backgrounds
      (phenotypes and genotypes) were observed, mostly with enrichment and antibiotic
      selective media. E. coli was detected in 13 samples (n=78; all types and 4
      brands; phylogenetic groups A, B1 and D; none STEC) with resistance to
      tetracycline [72%; tet(A) and/or tet(B)], streptomycin (58%; aadA and/or strA
      strB), sulfamethoxazole (50%; sul1 and/or sul2), trimethoprim (50%; dfrA1 or
      dfrA12), ampicillin (49%; blaTEM), nalidixic acid (36%), ciprofloxacin (5%) or
      chloramphenicol (3%; catA). E. coli clones, including the widespread group
      D/ST69, were detected in different samples from the same brand or different
      brands pointing out to a potential cross-contamination. Other clinically relevant
      resistance genes were detected in 2 Raoultella terrigena carrying a bla(SHV-2)
      and 1 Citrobacter freundii isolate with a qnrB9 gene. Among Enterococcus (n=108;
      35 samples; Enterococcus casseliflavus--40, Enterococcus faecalis--20,
      Enterococcus faecium--18, Enterococcus hirae--9, Enterococcus gallinarum--5, and
      Enterococcus spp.--16) resistance was detected for tetracyclines [6%; tet(M)
      and/or tet(L)], erythromycin [3%; erm(B)], nitrofurantoin (1%) or ciprofloxacin
      (1%). The present study places ready-to-eat salads within the spectrum of
      ecological niches that may be vehicles for antibiotic resistance bacteria/genes
      with clinical interest (e.g. E. coli-D-ST69; bla(SHV-2)) and these findings are
      worthy of attention as their spread to humans by ingestion cannot be dismissed.

PMID- 24036262
TI  - Use of quantitative microbial risk assessment when investigating foodborne
      illness outbreaks: the example of a monophasic Salmonella Typhimurium 4,5,12:i:-
      outbreak implicating beef burgers.
AB  - A major community outbreak of salmonellosis occurred in France in October 2010.
      Classical epidemiological investigations led to the identification of beef
      burgers as the cause of the outbreak and the presence of the emerging monophasic
      Salmonella Typhimurium 4,5,12:i:-. The objective of this study was to understand
      the events that led to this large outbreak, that is to say, what are the
      contributing factors associated with consumer exposure to Salmonella. To this
      end, intensive microbiological investigations on several beef burgers were
      conducted and a risk assessment model was built. The microbiological results
      confirm the presence of Salmonella in all analysed frozen burgers at high levels
      of contamination above 1000 MPN/g. These results in frozen burgers combined with
      a model of thermal destruction were used to estimate the dose ingested by the
      exposed persons. Most people that consumed cooked beef burgers were exposed from
      1.6 to 3.1 log10 (MPN). The number of sick people predicted with a dose-response
      relationship for Salmonella is consistent with the observed number of
      salmonellosis cases. The very high initial contamination level in frozen beef
      burgers is the primary cause of this large outbreak rather than bad cooking
      practices. Intensive investigations, modelling of the initial contamination and
      quantitative exposure and risk assessments are complementary to epidemiological
      investigation. They can be valuable elements for the assessment of missing
      information or the identification of the primary causes of outbreaks.

PMID- 24036263
TI  - Ferulic acid attenuates focal cerebral ischemia-induced decreases in p70S6 kinase
      and S6 phosphorylation.
AB  - Ferulic acid exhibits neuroprotective effects against focal cerebral ischemia.
      PI3/K and Akt signaling pathways play an essential role in protecting against
      cerebral ischemia. Mammalian target of rapamycin (mTOR), a major downstream
      target of Akt, regulates p70S6 kinase and S6, both of which are involved in
      ribosomal biogenesis and protein synthesis. I investigated whether ferulic acid
      regulates mTOR, p70S6 kinase, and S6 phosphorylation during brain ischemic
      injury. Rats were treated immediately with vehicle or ferulic acid (100mg/kg,
      i.v.) after middle cerebral artery occlusion (MCAO). Brains tissues were removed
      at 24h after the onset of MCAO and the cerebral cortex regions were collected.
      Ferulic acid reduced the MCAO-induced infarct volume. I showed previously that
      ferulic acid prevents the MCAO injury-induced decrease of Akt phosphorylation. In
      this study, MCAO injury induced decreases in mTOR, p70S6 kinase, and S6
      phosphorylation levels, while ferulic acid attenuated the injury-induced
      decreases. Immunohistochemical staining demonstrated that ferulic acid prevented
      the MCAO-induced reduction in the number of positive cells for phosphorylated
      p70S6 kinase and phosphorylated S6. These findings suggest that ferulic acid has
      a neuroprotective function against focal cerebral ischemia by modulating p70S6
      kinase expression and S6 phosphorylation. 

PMID- 24036264
TI  - Experimental and theoretical study of p-nitroacetanilide.
AB  - The spectroscopic properties of the p-nitroacetanilide (PNA) were examined by FT
      IR, FT-Raman and UV-Vis techniques. FT-IR and FT-Raman spectra in solid state
      were observed in the region 4000-400 cm(-1) and 3500-100 cm(-1), respectively.
      The UV-Vis absorption spectrum of the compound that dissolved in ethanol was
      recorded in the range of 200-400 nm. The structural and spectroscopic data of the
      molecule in the ground state were calculated by using density functional theory
      (DFT) employing B3LYP methods with the 6-31G(d,p) and 6-311+G(d,p) basis sets.
      The geometry of the molecule was fully optimized, vibrational spectra were
      calculated and fundamental vibrations were assigned on the basis of the total
      energy distribution (TED) of the vibrational modes, calculated with scaled
      quantum mechanics (SQM) method. Thermodynamic properties like entropy, heat
      capacity and enthalpy have been calculated for the molecule. HOMO-LUMO energy gap
      has been calculated. The intramolecular contacts have been interpreted using
      natural bond orbital (NBO) and natural localized molecular orbital (NLMO)
      analysis. Important non-linear optical (NLO) properties such as electric dipole
      moment and first hyperpolarizability have been computed using B3LYP quantum
      chemical calculation.

PMID- 24036265
TI  - The naive effector cells of collagen type I during acute experimental
      pancreatitis are acinar cells and not pancreatic stellate cells.
AB  - OBJECTIVE: The purpose of this study was to investigate the expression of
      collagen type I and the mRNA level of its regulatory factor, TGF-beta1, in tissue
      samples of acute pancreatitis and to determine the significance of collagen type
      I in predisposition to pancreatic fibrosis during acute pancreatitis. METHODS:
      Sprague-Dawley rats were divided into an experimental group (30 rats) and a
      control group (12 rats). The rats in the experimental group were
      intraperitoneally injected with cerulein to induce acute pancreatitis. The
      distribution and expression of collagen type I in the pancreatic tissues were
      examined by immunohistochemical staining. The mRNA level of TGF-beta1 was
      determined by real-time polymerase chain reaction (PCR). RESULTS: (1) Collagen
      type I was localized in the cytoplasm of pancreatic acinar cells. With
      pancreatitis progressed, strong positive staining for collagen type I covered
      whole pancreatic lobules, whereas, the islet tissue, interlobular area, and
      pancreatic necrotic area were negative for collagen type I. (2) The level of TGF
      beta1 mRNA in rats from the experimental group increased gradually the
      establishment of acute pancreatitis, and was significantly higher than that in
      the control group at every time point. CONCLUSIONS: (1) During acute
      pancreatitis, pancreatic acinar cells, not pancreatic stellate cells as
      traditionally believed, were the naive effector cells of collagen type I. (2) TGF
      beta1 played a key role in regulating collagen I expression during acute
      pancreatitis.

PMID- 24036266
TI  - 2-Aminoethyl diphenylborinate (2-APB) analogues: regulation of Ca2+ signaling.
AB  - In order to obtain compounds with modified 2-APB activities, we synthesized
      number of 2-APB analogues and analyzed their inhibitory activities for SOCE. The
      IC50 of 2-APB for SOCE inhibition is 3 MUM while IC50 of some of our 2-APB
      analogues range 0.1-10 MUM. The adducts of amino acids with diphenyl borinic acid
      have strong inhibitory activities. By using these compounds, we will be able to
      regulate intracellular Ca(2+) concentration and consequent cellular processes
      more efficiently than with 2-APB.

PMID- 24036268
TI  - Identification of short-lived long non-coding RNAs as surrogate indicators for
      chemical stress response.
AB  - Abiotic and biotic stressors in human cells are often a result of sudden and/or
      frequent changes in environmental factors. The molecular response to stress
      involves elaborate modulation of gene expression and is of homeostatic,
      ecological, and evolutionary importance. Although attention has primarily focused
      on signaling pathways and protein networks, long non-coding RNAs (ncRNAs) are
      increasingly involved in the molecular mechanisms associated with responses to
      cellular stresses. We identified six novel short-lived long ncRNAs (MIR22HG,
      GABPB-AS1, LINC00152, IDI2-AS1, SNHG15, and FLJ33630) that responded to chemical
      stressors (cisplatin, cycloheximide, and mercury (II) oxide) in HeLa Tet-off
      cells. Our results indicate that short-lived long ncRNAs respond to general and
      specific chemical stressors. The expression levels of the short-lived long ncRNAs
      were elevated because of prolonged decay rates in response to chemical stressors
      and interruption of RNA degradation pathways. We propose that these long ncRNAs
      have the potential to be surrogate indicators of cellular stress responses.

PMID- 24036267
TI  - Differentiation of reprogrammed human adipose mesenchymal stem cells toward
      neural cells with defined transcription factors.
AB  - Somatic cell reprogramming may become a powerful approach to generate specific
      human cell types for cell-fate determination studies and potential
      transplantation therapies of neurological diseases. Here we report a
      reprogramming methodology with which human adipose stem cells (hADSCs) can be
      differentiated into neural cells. After being reprogrammed with polycistronic
      plasmid carrying defined factor OCT3/4, SOX2, KLF4 and c-MYC, and further treated
      with neural induce medium, the hADSCs switched to differentiate toward neural
      cell lineages. The generated cells had normal karyotypes and exogenous vector
      sequences were not inserted in the genomes. Therefore, this cell lineage
      conversion methodology bypasses the risk of mutation and gene instability, and
      provides a novel strategy to obtain patient-specific neural cells for basic
      research and therapeutic application.

PMID- 24036269
TI  - Hepatocyte clearance and pharmacokinetics of recombinant factor IX glycosylation
      variants.
AB  - Addition of N-linked glycosylation sites has been shown to increase serum half
      life and decrease clearance for proteins such as recombinant erythropoietin
      (EPO). However, factor IX (FIX) variants with additional N-linked glycans ("HG"
      variants) that were expressed in HKB11 cells showed increased clearance in rat in
      vivo pharmacokinetic studies relative to FIX variants with no additional glycans.
      Variants with multiple additional glycans were the most rapidly cleared. A rat
      hepatocyte clearance assay was developed to measure intrinsic clearance of these
      FIX variants in vitro. The rank order of clearance of the variants was the same
      both in vivo and in the in vitro hepatocyte assay. In the in vitro assay,
      heparin, galactose, and asialo-orosomucoid inhibited clearance of a FIX HG
      variant by hepatocytes, and asialo-FIX was rapidly cleared, suggesting roles for
      the asialoglycoprotein receptor (ASGPR) and cell surface proteoglycans in FIX
      clearance. Thus the in vitro hepatocyte intrinsic clearance assay is both useful
      and predictive for identifying rapidly cleared recombinant proteins and for
      helping to identify receptors involved in clearance of proteins by the liver. 

PMID- 24036270
TI  - A novel chronic stress-induced shift in the Th1 to Th2 response promotes colon
      cancer growth.
AB  - Epidemiological data have shown that stress and other psychological factors might
      influence cancer onset and progression. However, to date, the mechanisms are not
      well understood. In the present study, we used chronic exposure to a scream as a
      novel form of sound stress to explore the influence of the chronic stress burden
      on colon cancer progression, and changes in the immune system were observed.
      Chronic exposure to scream sound stress induced freezing behavior in the mice and
      decreased the bodyweight gain. It also caused changes in the adrenal gland and
      increased serum corticosterone and norepinephrine levels. Cytokine microarray
      analysis showed changes in the levels of Th1 and Th2 cytokines. The chronic
      scream sound stress caused a shift from the Th1 to the Th2 response both in the
      circulation and in tumor-infiltrated lymphocytes, and it promoted colon cancer
      progression significantly. Taken together, chronic scream sound stress can be
      conveniently used as a novel chronic stress model. Chronic stress contributes to
      colon cancer progression and induces a Th1/Th2 imbalance in the mouse immune
      system, which is considered critical during cancer progression.

PMID- 24036271
TI  - CREB, another culprit for TIGAR promoter activity and expression.
AB  - Cellular expression of the TP53-induced glycolysis and apoptosis regulator
      (TIGAR) protein results in the down-regulation of glycolysis, reduction of
      intracellular levels of reactive oxygen species, and protection from apoptosis.
      However, despite its biological importance, the mechanisms that regulate its
      expression remain obscure. The bioinformatic analysis performed in this study
      indicates that the TIGAR promoter region is highly conserved among species.
      Further analysis using 5'-deletion analysis and site-directed mutagenesis
      demonstrated that the region at -4/+13 contained a cAMP-response element (CRE).
      EMSA and chromatin immunoprecipitation showed that the site was recognized by CRE
      binding protein (CREB). Furthermore, knockdown of CREB substantially reduced
      promoter activity and TIGAR expression in cells. In addition, over-expression of
      either CREB or forskolin enhanced promoter activity and TIGAR expression. These
      results provide evidence that CREB regulates TIGAR expression via a CRE-binding
      site at the TIGAR promoter.

PMID- 24036272
TI  - Natural cardiogenesis-based template predicts cardiogenic potential of induced
      pluripotent stem cell lines.
AB  - BACKGROUND: Cardiac development is a complex process resulting in an integrated,
      multilineage tissue with developmental corruption in early embryogenesis leading
      to congenital heart disease. Interrogation of individual genes has provided the
      backbone for cardiac developmental biology, yet a comprehensive transcriptome
      derived from natural cardiogenesis is required to gauge innate developmental
      milestones. METHODS AND RESULTS: Stage-specific cardiac structures were dissected
      from 8 distinctive mouse embryonic time points to produce genome-wide expressome
      analysis across cardiogenesis. With reference to this native cardiogenic
      expression roadmap, divergent induced pluripotent stem cell-derived cardiac
      expression profiles were mapped from procardiogenic 3-factor (SOX2, OCT4, KLF4)
      and less-cardiogenic 4-factor (plus c-MYC) reprogrammed cells. Expression of
      cardiac-related genes from 3-factor-induced pluripotent stem cell differentiated
      in vitro at days 5 and 11 and recapitulated expression profiles of natural
      embryos at days E7.5-E8.5 and E14.5-E18.5, respectively. By contrast, 4-factor
      induced pluripotent stem cells demonstrated incomplete cardiogenic gene
      expression profiles beginning at day 5 of differentiation. Differential gene
      expression within the pluripotent state revealed 23 distinguishing candidate
      genes among pluripotent cell lines with divergent cardiogenic potentials. A
      confirmed panel of 12 genes, differentially expressed between high and low
      cardiogenic lines, was transformed into a predictive score sufficient to
      discriminate individual induced pluripotent stem cell lines according to relative
      cardiogenic potential. CONCLUSIONS: Transcriptome analysis attuned to natural
      embryonic cardiogenesis provides a robust platform to probe coordinated cardiac
      specification and maturation from bioengineered stem cell-based model systems. A
      panel of developmental-related genes allowed differential prognosis of
      cardiogenic competency, thus prioritizing cell lines according to natural
      blueprint to streamline functional applications.

PMID- 24036274
TI  - Adhesion, but not a specific cadherin code, is indispensable for ES cell and
      induced pluripotency.
AB  - Embryonic stem (ES) cell pluripotency and induced pluripotent stem (iPS) cell
      generation is dependent on a core transcriptional network and proper cell-cell
      adhesion mediated by E-cadherin (E-cad). Whereas E-cad is associated with
      pluripotency, N-cadherin (N-cad) expression is correlated with differentiation
      into mesodermal and neuroectodermal lineages. We investigated whether E-cad
      harbors unique molecular features in establishing or maintaining pluripotency. By
      using a gene replacement knock-in (ki) approach to express N-cadherin (N-cad) or
      E-cad/N-cad chimeric cadherins under the control of the E-cad locus, we show that
      all E-cad-depleted ki/ki ES cells are maintained in an undifferentiated state.
      Surprisingly, these cells retained key features of pluripotency, such as Nanog
      expression and full differentiation capacity in vitro and in vivo, whereas E-cad
      knockout (ko) ES cells irreversibly lost most of these features. Moreover, our
      results indicate that E-cad mediated adhesion is essential for iPS cell
      generation, since E-cad depleted fibroblasts were not reprogrammed. In contrast,
      N-cad efficiently supports somatic reprogramming similar to E-cad, and permits
      initiation of the crucial initial step of mesenchymal-epithelial transition.
      Thus, we show that cell adhesion and a robust pluripotent phenotype are
      ultimately connected. Since N-cad properly compensates for loss of E-cad, no
      specific 'cadherin code' is required. 

PMID- 24036275
TI  - A multi-stage compartmental model for HIV-infected individuals: I--waiting time
      approach.
AB  - Traditionally, epidemic processes have focused on establishing systems of
      differential-difference equations governing the number of individuals at each
      stage of the epidemic. Except for simple situations such as when transition rates
      are linear, these equations are notoriously intractable mathematically. In this
      work, the process is described as a compartmental model. The model also allows
      for individuals to go directly from any prior compartment directly to a final
      stage corresponding to death. This allows for the possibility that individuals
      can die earlier due to some non-disease related cause. Then, the model is based
      on waiting times in each compartment. Survival probabilities of moving from a
      given compartment to another compartment are established. While our approach can
      be used for general epidemic processes, our framework is for the HIV/AIDS
      process. It is then possible to establish the impact of the HIV/AIDS epidemic
      process on, e.g., insurance premiums and payouts and health-care costs. The
      effect of changing model parameter values on these entities is investigated. 

PMID- 24036276
TI  - Evaluation of sildenafil pressurized metered dose inhalers as a vasodilator in
      umbilical blood vessels of chicken egg embryos.
AB  - Sildenafil citrate is a selective phosphodiesterase-5 inhibitor used for the
      treatment for erectile dysfunction and pulmonary hypertension. The delivery of
      sildenafil directly to the lung could have several advantages over conventional
      treatments for pulmonary hypertension because of the local delivery, a more rapid
      onset of response, and reduced side effects. The major problem of sildenafil
      citrate is its limited solubility in water. Sildenafil citrate was complexed with
      cyclodextrins (CDs) to enhance its water solubility prior to development as an
      inhaled preparation. Four sildenafil citrate inhaled formulations were prepared
      with the aid of HP-beta-CD (#1), alpha-CD (#2) and gamma-CD (#3) and their
      effects were compared with the formulations without CDs (#4). The sildenafil
      citrate pressurized metered dose inhalers (pMDI) used ethanol as a solvent,
      PEG400 as a stabilizing agent, sorbitan monooleate as a surfactant and HFA-134a
      as a propellant. All formulations consisted of sildenafil citrate equivalent to a
      sildenafil content of 20MUg/puff. These products were evaluated according to a
      standard guideline of inhalation products. Vasodilation testing was performed to
      investigate the efficacy of sildenafil pMDIs in relieving a vasoconstricted
      umbilical blood vessel of the chicken egg embryo. The sildenafil contents of the
      pMDI formulations #1-#3 were within the acceptance criteria (80-120%). The
      emitted doses (ED) were 102.3+/-11.5%, the fine particle fractions (FPF) were
      60.5+/-5.6% and the mass median aerodynamic diameters (MMAD) were 2.3+/-0.3MUm.
      The vasodilatory activity of those formulations reduced umbilical blood pressure
      by 67.1-73.7% after treatment by intravenous injection whereas only a 50.1-58.0%
      reduced blood pressure was obtained after direct spraying of the sildenafil pMDI
      containing CDs. With sildenafil formulations of a pMDI without CD the blood
      pressure was reduced by only 39.0% (P-value<0.05). The available sildenafil in
      the blood vessels of chicken egg embryos after spraying sildenafil-CDs pMDIs was
      within the range of 751-825ng/mL which was much higher than that of a sildenafil
      only pMDI. 

PMID- 24036277
TI  - Disclosing incidental findings in genetics contexts: a review of the empirical
      ethical research.
AB  - The disclosure of incidental findings, also called unsolicited findings,
      unexpected results, and secondary variants, is increasingly recognised as an
      issue in clinical and research genetics contexts. The rise of next generation
      sequencing methods has only intensified the issue, increasing the likelihood of
      incidental findings appearing. This review focuses on empirical research on the
      ethical issues involved. Electronic databases were searched for articles covering
      quantitative and qualitative research on the ethical issues involved in the
      disclosure of incidental findings in clinical and research genetics contexts. 16
      articles were ultimately accepted for review. Data was extracted and synthesised
      on the factors that should be taken into account during the decision-making
      process surrounding the disclosure of an incidental finding in a genetics
      context. These factors include the possibility of disclosure, various practical
      and technical factors, and various ethical factors. We suggest the development of
      a decision-making tree, involving an exploration of the practical and ethical
      concerns raised by the studies. This is in our view the best way of handling the
      wide variety of both possible incidental findings and parties interested in the
      disclosure of incidental findings. 

PMID- 24036278
TI  - Balancing crosstalk between 20-hydroxyecdysone-induced autophagy and caspase
      activity in the fat body during Drosophila larval-prepupal transition.
AB  - In the fruitfly, Drosophila melanogaster, autophagy and caspase activity function
      in parallel in the salivary gland during metamorphosis and in a common regulatory
      hierarchy during oogenesis. Both autophagy and caspase activity progressively
      increase in the remodeling fat body, and they are induced by a pulse of the
      molting hormone (20-hydroxyecdysone, 20E) during the larval-prepupal transition.
      Inhibition of autophagy and/or caspase activity in the remodeling fat body
      results in 25-40% pupal lethality, depending on the genotypes. Interestingly, a
      balancing crosstalk occurs between autophagy and caspase activity in this tissue:
      the inhibition of autophagy induces caspase activity and the inhibition of
      caspases induces autophagy. The Drosophila remodeling fat body provides an in
      vivo model for understanding the molecular mechanism of the balancing crosstalk
      between autophagy and caspase activity, which oppose with each other and are
      induced by the common stimulus 20E, and blockage of either path reinforces the
      other path.

PMID- 24036279
TI  - Genetic marking of sex using a W chromosome-linked transgene.
AB  - Many species belonging to the order Lepidoptera are major pests in agriculture
      and arboriculture. The sterile insect technique (SIT) is an eco-friendly and
      highly efficient genetically targeted pest management approach. In many cases, it
      is preferable to release only sterile males in an SIT program, and efficient
      sexing strategies are crucial to the successful large-scale implementation of
      SIT. In the present study, we established 160 transgenic silkworm (Bombyx mori)
      lines to test the possibility of genetic sexing using a W chromosome-linked
      transgene, which is thought to be the best sexing strategy for lepidopteran
      species. One transgenic line with a female-specific expression pattern of
      reporter gene was obtained. The expression level of the W-linked transgene was
      comparable with autosomal insertions and was stable for 17 continuous
      generations. Molecular characterization showed this line contained a single copy
      of the reporter gene on the W chromosome, and the integration site was TTAG in
      contig W-BAC-522N19-C9. The feasibility of using a W chromosome-linked transgene
      demonstrated here and the possible improvements discussed will provide valuable
      information for other lepidopteran pests. The novel W chromosome-linked
      transgenic line established in this study will serve as an important resource for
      fundamental research with the silkworm B. mori. 

PMID- 24036280
TI  - Influence of biocorrosion on microstructure and mechanical properties of deformed
      Mg-Y-Er-Zn biomaterial containing 18R-LPSO phase.
AB  - The microstructure and mechanical properties of as-extruded Mg-8Y-1Er-2Zn (wt%)
      alloy containing long period stacking ordered (LPSO) phase are comparatively
      investigated before and after corrosion in a simulated body fluid (SBF) at 37
      degrees C. The as-extruded alloy consists of a long strip-like 18R-LPSO phase and
      some fine lamellae grains formed by primary recrystallization during the
      extrusion process. The hydrogen evolution volume per day fluctuates between 0.21
      and 0.32ml/cm(2) in the immersion test for 240h, and the corresponding corrosion
      rate is calculated as 0.568mm/y. The corrosion product is determined as Mg(OH)2,
      whilst a Ca(H2PO4)2 compound is also observed on the surface of the samples. The
      corrosion site preferentially occurs at the interface between LPSO phase and Mg
      matrix. Before immersing, the tensile yield strength (TYS), ultimate tensile
      strength (UTS) and elongation of the alloy are 275MPa, 359MPa, and 19%,
      respectively. More attractively, these mechanical properties can be maintained
      even after immersing in SBF for 240h (TYS, UTS and elongation are 216MPa, 286MPa
      and 6.8%, respectively) because of the existence of high anti-corrosion LPSO
      phase. 

PMID- 24036273
TI  - Exploiting nanotechnology to overcome tumor drug resistance: Challenges and
      opportunities.
AB  - Tumor cells develop resistance to chemotherapeutic drugs through multiple
      mechanisms. Overexpression of efflux transporters is an important source of drug
      resistance. Efflux transporters such as P-glycoprotein reduce intracellular drug
      accumulation and compromise drug efficacy. Various nanoparticle-based approaches
      have been investigated to overcome efflux-mediated resistance. These include the
      use of formulation excipients that inhibit transporter activity and co-delivery
      of the anticancer drug with a specific inhibitor of transporter function or
      expression. However, the effectiveness of nanoparticles can be diminished by poor
      transport in the tumor tissue. Hence, adjunct therapies that improve the
      intratumoral distribution of nanoparticles may be vital to the successful
      application of nanotechnology to overcome tumor drug resistance. This review
      discusses the mechanisms of tumor drug resistance and highlights the
      opportunities and challenges in the use of nanoparticles to improve the efficacy
      of anticancer drugs against resistant tumors.

PMID- 24036282
TI  - Binding sites and hydrophobic pockets in Human Thioredoxin 1 determined by normal
      mode analysis.
AB  - The Thioredoxin (Trx) system plays important roles in several diseases (e.g.
      cancer, viral infections, cardiovascular and neurodegenerative diseases).
      Therefore, there is a therapeutic interest in the design of modulators of this
      system. In this work, we used normal mode analysis to identify putative binding
      site regions for Human Trx1 that arise from global motions. We identified three
      possible inhibitor's binding regions that corroborate previous experimental
      findings. We show that intrinsic motions of the protein are related to the
      exposure of hydrophobic regions and non-active site cysteines that could
      constitute new binding sites for inhibitors. 

PMID- 24036281
TI  - Maximizing the potential of electron cryomicroscopy data collected using direct
      detectors.
AB  - Single-particle electron cryomicroscopy is undergoing a technical revolution due
      to the recent developments of direct detectors. These new recording devices
      detect electrons directly (i.e. without conversion into light) and feature
      significantly improved detective quantum efficiencies and readout rates as
      compared to photographic films or CCDs. We evaluated here the potential of one
      such detector (Gatan K2 Summit) to enable the achievement of near-atomic
      resolution reconstructions of biological specimens when coupled to a widely used,
      mid-range transmission electron microscope (FEI TF20 Twin). Compensating for beam
      induced motion and stage drift provided a 4.4A resolution map of Sulfolobus
      turreted icosahedral virus (STIV), which we used as a test particle in this
      study. Several motion correction and dose fractionation procedures were explored
      and we describe their influence on the resolution of the final reconstruction. We
      also compared the quality of this data to that collected with a FEI Titan Krios
      microscope equipped with a Falcon I direct detector, which provides a benchmark
      for data collected using a high-end electron microscope. 

PMID- 24036283
TI  - Lipid inhibitors of high affinity glycine transporters: identification of a novel
      class of analgesics.
AB  - Glycine plays a key role in regulating inhibitory neurotransmission in the spinal
      cord and concentrations of glycine in the CNS are regulated by two subtypes of
      high affinity glycine transporters, GlyT1 and GlyT2. In this mini review we will
      discuss a series of lipid inhibitors of GlyT2 that show promise as analgesics in
      the treatment of neuropathic and inflammatory pain. N-arachidonyl-glycine
      inhibits the rate of transport by GlyT2, but has very little or no activity on
      GlyT1. We will discuss structure-activity studies of the actions of related
      lipids on GlyT2 and also the characterization of a more potent lipid inhibitor of
      GlyT2, oleoyl-l-carnitine. Both N-arachidonyl-glycine and oleoyl-l-carnitine show
      specificity for GlyT2 over GlyT1, which has allowed the use of chimeric
      GlyT1/GlyT2 transporters to begin characterizing the molecular basis for
      specificity and mechanism of action of these lipid inhibitors. Although our
      understanding of the molecular basis for lipid inhibition is still in its
      infancy, it appears that extracellular loop 4 of GlyT2 plays an important role in
      the inhibitory mechanism. 

PMID- 24036284
TI  - Oxidative modification of serum proteins in multiple sclerosis.
AB  - Multiple sclerosis (MS) has been demonstrated to involve oxidative stress and
      augmented glycoxidation. In this study, several markers of protein oxidative
      damage and glycoxidation have been compared in 14 relapsing remittent in MS
      (RRMS) patients without immunomodifying treatment, 10 patients in clinical
      relapse, and clinically stable patient groups treated with interferon beta 1a
      (18) , beta 1b (19) and glatiramer acetate (GA; 6) in relation to healthy
      subjects (12). The glycophore content was increased in RRSM patients without
      treatment and in patients treated with GA. The level of advanced protein
      oxidation products (AOPP) was increased in RRSM patients without treatment and in
      patients with clinical relapse. The level of protein carbonyls was elevated in
      RRSM patients without treatment and in patients treated with interferon beta 1b.
      The levels of dityrosine level and N'-formylkynureine were elevated in RRSM
      patients without treatment while serum protein thiol groups were decreased in
      RRSM patients in clinical relapse as well as RRMS patients treated with
      interferon beta 1a. Several markers of protein modification showed correlation
      with the C-reactive protein level and white blood cell count, suggesting that
      oxidative protein modifications are linked to the inflammatory processes in MS.
      Results of this study confirm the occurrence of protein oxidative and
      glycoxidative damage in MS and show that spectrophotometric and fluorimetric
      markers of this damage, especially the AOPP level, may be useful in monitoring
      oxidative stress in the course of therapy of MS.

PMID- 24036285
TI  - Angiocidin induces differentiation of acute myeloid leukemia cells.
AB  - Acute myeloid leukemia (AML) is a malignant proliferative disorder in which
      leukemic cells fail to terminally differentiate and accumulate in the blood and
      bone marrow. Standard AML therapy requires intensive chemotherapy with a low rate
      of durable remission and is associated with significant treatment-related
      toxicity, especially in elderly patients. Therefore, new therapeutic options for
      the treatment of AML are urgently needed. We previously reported that the novel
      angiogenic inhibitor, angiocidin, induces differentiation of monocytes to
      macrophages. Here we investigate the effects of angiocidin on AML cells lines and
      primary AML cells. Differentiation was assessed by flow cytometry measuring the
      increase in expression of cell surface marker characteristic of normal
      macrophages. Four AML cell lines (THP-1, Mono-mac-1, HL-60 and MV4-11) and 5 of
      10 primary human AML samples showed evidence of differentiation when cultured in
      vitro for 24 h with 10 MUg/mL angiocidin. Additionally, we found that angiocidin
      promoted secretion of a number of cytokines from the cell lines as well as
      patient cells. We next evaluated the effect of angiocidin on a xenotransplanted
      primary human AML sample engrafted in NSG mice. We found angiocidin monotherapy
      reduced the human AML burden in bone marrow by 63% relative to untreated control.
      Interestingly, angiocidin+cytosine arabinoside (Ara-C) combination therapy
      reduced human AML in bone marrow by 79%. We believe the combination of in vitro
      data supporting the capacity of angiocidin to drive differentiation in multiple
      AML cell lines and primary human AML samples and its activity in a
      xenotransplantation model that reproduces the human disease is significant. These
      observations support the continued evaluation and development of angiocidin as a
      potential novel, non-toxic therapy for AML.

PMID- 24036288
TI  - Editorial.

PMID- 24036289
TI  - A review of non-communicable disease in low- and middle-income countries.
AB  - Non-communicable disease (NCD)-primarily heart and stroke disease, cancer,
      chronic obstructive pulmonary disease and diabetes-caused an estimated 35 million
      deaths in 2005, 80% of which occurred in low- and middle-income countries
      (LAMICs). By 2030, 8 of 10 leading causes of death will be linked to these
      conditions. The burden of NCDs poses serious implications for social and economic
      development worldwide but particularly for LAMICs. WHO and member states have
      developed a clear vision represented by the Global Strategy for the Prevention
      and Control of Noncommunicable Diseases and an implementation plan to tackle this
      epidemic, incorporating lessons learned from international experience and the
      work of WHO in member states. The 2008 NCD Action Plan, which advocates an
      integrated approach to NCD prevention and control, with emphasis on the role of
      primary health care, is based on current scientific knowledge, available evidence
      and a review of international experience. It comprises a set of actions to tackle
      the growing public-health burden imposed by NCDs. For the plan to be implemented
      successfully, high-level political commitment and the concerted involvement of
      governments, communities and health-care providers are required; in addition,
      public-health policies will need to be reoriented and allocation of resources
      improved. 

PMID- 24036287
TI  - PainNetworks: a web-based resource for the visualisation of pain-related genes in
      the context of their network associations.
AB  - Hundreds of genes are proposed to contribute to nociception and pain perception.
      Historically, most studies of pain-related genes have examined them in isolation
      or alongside a handful of other genes. More recently the use of systems biology
      techniques has enabled us to study genes in the context of the biological
      pathways and networks in which they operate. Here we describe a Web-based
      resource, available at http://www.PainNetworks.org. It integrates interaction
      data from various public databases with information on known pain genes taken
      from several sources (eg, The Pain Genes Database) and allows the user to examine
      a gene (or set of genes) of interest alongside known interaction partners. This
      information is displayed by the resource in the form of a network. The user can
      enrich these networks by using data from pain-focused gene expression studies to
      highlight genes that change expression in a given experiment or pairs of genes
      showing correlated expression patterns across different experiments. Genes in the
      networks are annotated in several ways including biological function and drug
      binding. The Web site can be used to find out more about a gene of interest by
      looking at the function of its interaction partners. It can also be used to
      interpret the results of a functional genomics experiment by revealing putative
      novel pain-related genes that have similar expression patterns to known pain
      related genes and by ranking genes according to their network connections with
      known pain genes. We expect this resource to grow over time and become a valuable
      asset to the pain community. 

PMID- 24036286
TI  - Opioid therapy for chronic pain in the United States: promises and perils.
AB  - Opioid therapy offers the promise of reducing the burden of chronic pain in not
      just individual patients, but among the broad population of patients with chronic
      pain. Randomized trials have demonstrated that opioid therapy for up to 12
      16weeks is superior to placebo, but have not addressed longer-term use. In the
      United States, opioid sales have quadrupled during 2000-2010, with parallel
      increases in opioid accidental overdose deaths and substance abuse admissions.
      Clinical use of long-term opioid therapy is characterized by a pattern of adverse
      selection, where high-risk patients are prescribed high-risk opioid regimens.
      This adverse selection may link these trends in use, abuse, and overdose. Long
      term opioid therapy appears to be associated with iatrogenic harm to the patients
      who receive the prescriptions and to the general population. The United States
      has, in effect, conducted an experiment of population-wide treatment of chronic
      pain with long-term opioid therapy. The population-wide benefits have been hard
      to demonstrate, but the harms are now well demonstrated. 

PMID- 24036290
TI  - Improving survival of children with severe acute malnutrition in HIV-prevalent
      settings.
AB  - The care of severely malnourished children in sub-Saharan Africa is challenging,
      especially in HIV-prevalent settings. Recent improvements to facility-based
      individual case management, and increased community-based management focusing on
      early identification and high programme coverage have led to reductions in
      mortality. Further interventions are urgently needed to address resistant
      mortality, mostly attributable to HIV. This paper explores strategies in three
      main areas to improve survival for children with severe acute malnutrition (SAM):
      identifying HIV and improving case management for HIV-infected children;
      strengthening existing strategies to improve outcomes for all children with SAM,
      regardless of HIV status; and improving early identification and increasing
      programme coverage. Although interventions to further improve survival among
      children with SAM in sub-Saharan Africa must firstly ensure best care for all
      children, HIV-infected children are at particular risks for mortality.
      Integration of specific interventions for HIV testing and treatment into SAM care
      is essential. International guidelines should reflect best evidence, and are in
      urgent need of updating and adapting to local country context. Effective
      interventions already exist that can improve survival in children with SAM in HIV
      prevalent settings. The challenge is to implement what we know and to research
      what we do not. 

PMID- 24036291
TI  - Old and new tick-borne rickettsioses.
AB  - The field of rickettsiology is rapidly evolving. Rickettsiae are small Gram
      negative bacteria that can be transmitted to humans by arthropods. In most cases
      they are transmitted transovarially in the arthropod; human beings are incidental
      hosts. In recent years the use of cell culture and molecular biology has
      profoundly changed our knowledge of rickettsiae and has led to the description of
      several new species. New rickettsial diseases have been found in three main
      situations: firstly, in places where no new species have been identified, typical
      rickettsial symptoms have been observed (Japan, China); secondly, typical
      rickettsioses have been found to be caused by different organisms - in such cases
      a new Rickettsia species has been misdiagnosed as a previously identified
      bacterium (for example, R. parkeri was confused with R. rickettsii); thirdly,
      atypical clinical symptoms have been found to be caused by rickettsial organisms
      such as R. slovaca. These findings challenge the old dogma that only one tick
      borne rickettsiosis is prevalent in one geographical area. Many Rickettsia spp.
      have been identified in ticks, but have not yet been implicated in human
      pathology. These rickettsiae should be considered as potential pathogens. All
      known or suspected rickettsial diseases should be treated (including in children)
      with doxycycline. 

PMID- 24036292
TI  - Global science and social movements: towards a rational politics of global
      health.
AB  - Tropical medicine as a discipline was originally limited to those diseases that
      are the consequence of the ecology of disease in the tropics. Over the past 100
      years we have come to realise that this limitation was the consequence of an
      historical snapshot. The commonality of human experience throughout the world
      speaks to our common biology and has led to the articulation of Global Health. We
      lack a coherent understanding of Global Health but its reach is beyond that of
      governments and entails concepts of justice and humanity as well as biomedicine
      and all the attendant semi-congruent disciplines. The development of Global
      Health will redefine the roles of all the stakeholders in the international
      health community be they individuals, institutions, agencies or medical journals.
      At present the gestation of Global Health involves the chaotic tumbling, rumbling
      and knocking together of ideas and aspirations. The hope must be that the outcome
      will be the highest attainable standard of health for all if not the
      perfectibility of humankind. 

PMID- 24036293
TI  - Lessons from community participation in health programmes: a review of the post
      Alma-Ata experience.
AB  - The year 2008 marked the 30 year anniversary of Primary Health Care, the health
      policy of all member nations of the WHO. Community participation was one of the
      key principles of this policy. This article reviews the experiences of and
      lessons learned by policy makers, planners and programme managers in attempting
      to integrate community participation into their health programmes. The lessons,
      identified in an earlier article by the author, are still relevant today. They
      help to identify three reasons why integrating community participation into
      health programmes is so difficult. These reasons are: (1) the dominance of the
      bio-medical paradigm as the main planning tool for programmes, leading to the
      view of community participation as an intervention; (2) the lack of in-depth
      analysis of the perceptions of community members regarding the use of community
      health workers; and (3) the propensity to use a framework that limits
      investigation into what works, why and how in community participation in health
      programmes. Despite these challenges, evidence suggests that community
      participation has contributed to health improvements at the local level,
      particularly in poor communities, and will continue to be relevant to programme
      professionals. 

PMID- 24036294
TI  - Examining Media Habits: implications for health promotion programs among the
      Toposa in Southern Sudan.
AB  - Dissemination of appropriate health education messages is essential to any health
      promotion campaign. This cross-sectional study examined media ownership, access
      and media preferences by target groups in Kapoeta South County, Southern Sudan.
      The target groups were segmented into household heads (n = 368); women with
      children under five years (n = 580); and youth 11-16 years old (n = 349).
      Interviewees were selected at random from 49 villages. Overall, a small portion
      owned radios (6.8%) and television sets (0.2%); more had access to radio (27.1%),
      listened to cassettes (50.8%), and had access to television and movies (21.4%).
      The majority were interested in programs developed in the vernacular (89.0%). A
      very low literacy rate (1.3%) and difficulty in understanding signage (29.7%)
      posed potential obstacles for use of print media as a primary source of health
      communication. Heads of household were more likely to own radios (P < 0.001),
      watch TV outside of the home (P = 0.034), and see posters (P = 0.038) than other
      groups. Traditional entertainment was attended by 94.4% of respondents.
      Information from chiefs (61.5%) and elders (51.5%) was considered trustworthy by
      the majority of respondents. This research highlights the utility in
      understanding media access, habits and preferences of community members when
      designing a health promotion campaign. 

PMID- 24036295
TI  - Seasonal variation among tuberculosis suspects in four countries.
AB  - The objective of the study was to analyze monthly trends across a calendar year
      in tuberculosis suspects and sputum smear-positive cases based on nationally
      representative samples of tuberculosis laboratory registers from Moldova,
      Mongolia, Uganda and Zimbabwe. Out of the 47 140 suspects registered in the
      tuberculosis laboratory registers, 13.4% (6312) were cases. The proportion varied
      from country to country, Moldova having the lowest (9%) and Uganda the highest
      (21%). From the monthly proportion of suspects and cases among total suspects and
      cases, seasonal variations were most marked in Mongolia which, among the four
      countries, also has the most pronounced seasonal variation in ambient
      temperature. Female suspects were consistently older than female cases in all
      four countries. Among males, male suspects were almost consistently older than
      male cases, most consistently in Moldova. Seasons seem to affect attendance to
      diagnostic laboratory services, evidenced by the contrasting findings of Mongolia
      (extreme continental northern climate) compared to Uganda (equatorial climate). A
      combination of external and possibly endogenous factors seems to determine
      whether tuberculosis suspects and cases present themselves to health care
      facilities. 

PMID- 24036296
TI  - Control of the Neglected Tropical Diseases in sub-Saharan Africa: the unmet
      needs.
AB  - The neglected tropical diseases (NTDs) are widespread in sub-Saharan Africa with
      several infecting many millions of individuals. Various integrated control
      programmes against up to seven NTDs are now being implemented in a few countries
      in sub-Saharan Africa, but the total coverage is estimated to be only a quarter
      of the population in need of treatment. We estimate that approximately $200+
      million per year is needed to fully implement the proposed integrated NTD control
      programmes in the rural populations in all the countries in sub-Saharan Africa,
      and an annual sum for 5-7 years would be needed to reduce morbidity to below
      public health importance. To date, the Bill & Melinda Gates Foundation, the
      United States Agency for International Development, the British Government,
      Geneva Global (an international philanthropic organisation) and other donors have
      committed some funds for NTD control; however, more effort is needed from a
      broader spectrum of donors to reach our targets. Unless more funds are committed
      and concerted actions are taken across all the sub-Saharan African countries,
      NTDs will be controlled in some but still be a major public health problem for
      the foreseeable future in the majority of countries. 

PMID- 24036297
TI  - Social deprivation index and lymphatic filariasis: a tool for mapping urban areas
      at risk in northeastern Brazil.
AB  - This paper describes the construction and application of a social deprivation
      index that was created to explore the relationship between lymphatic filariasis
      and socioenvironmental variables in the municipality of Jaboatao dos Guararapes,
      Pernambuco, Brazil, thereby contributing towards identifying priority areas for
      interventions. This indicator was obtained from principal-component factor
      analysis. Variables available from the national census representing
      socioenvironmental conditions, household characteristics and urban services were
      used. Epidemiological data came from a parasitological survey on lymphatic
      filariasis. 23 673 individuals were examined and 323 were positive (1.4%). Two
      factors that together explained 80.61% of the total variance were selected. The
      social deprivation strata were capable of indicating a risk gradient, with 74.9%
      of the microfilaremia cases situated in the high-risk stratum. Principal
      component factor analysis was shown to be sensitive for selecting indicators
      associated with the risk of lymphatic filariasis transmission and for detecting
      areas potentially at risk. The capacity of the social deprivation index for
      picking up social inequalities qualifies it as a new tool for use in planning
      interventions aimed at controlling lymphatic filariasis in urban spaces. 

PMID- 24036298
TI  - The Ifakara Health Institute's Bagamoyo Research and Training Centre: a well
      established clinical trials site in Tanzania.
AB  - Bagamoyo Research and Training Centre (BRTC), a branch of the Ifakara Health
      Institute (IHI), established in late 2004, has evolved into a leading site in
      performing high-quality Phase II and Phase III malaria vaccine and drug trials
      according to ICH/GCP standards. Several Phase II and III trials and assessments
      of interventions focused on better diagnosis, treatment and prevention of malaria
      have been completed successfully. Expansion into the areas of TB, with the set up
      of a new BSL-3, and HIV/AIDS marks the commitment of the site to developing into
      a regional centre of excellence for both clinical trials and epidemiological
      research. 

PMID- 24036299
TI  - Risk factors and true outcomes for lost to follow-up individuals in an
      antiretroviral treatment programme in Tete, Mozambique.
AB  - Scale-up of antiretroviral therapy (ART) in sub-Saharan Africa is a major public
      health priority, but ensuring long-term adherence to treatment is a growing
      concern. The objectives of this retrospective study were to determine risk
      factors and true outcomes for individuals lost to follow-up in a routine HIV/AIDS
      care programme in Tete, Mozambique. Between May 2002 and August 2007, 2818
      individuals were initiated on ART and 594 (21%) considered lost to follow-up were
      actively traced. Risk factors for being lost to follow-up were: age between 16
      and 35 years [odds ratio (OR) = 1.4, P = 0.009]; CD4 count <50 cells/MUl (OR =
      1.7, P < 0.001); time on ART <3 months (OR = 3.6, P < 0.001); tuberculosis
      infection (OR = 2.5, P < 0.001); and Kaposi's sarcoma infection (OR = 5.9, P <
      0.001). Sixty-four percent (380/594) of patients lost to follow-up could not be
      traced. Of the 214 (36%) that could be traced, 118 (55%) were dead, 43 (20%) were
      transferred out, 7 (3%) were misclassified and 46 (22%) were true defaulters.
      Active tracing should be conducted routinely to better understand the reasons for
      defaulting and to provide evidence for action. Early mortality may be reduced by
      enrolling patients in care as early as possible and providing optimal adherence
      counselling in the first months. 

PMID- 24036301
TI  - The Green synthesis of gold nanoparticles using an aqueous root extract of
      Morinda citrifolia L.
AB  - In the present work, we describe the synthesis of gold nanoparticles using an
      aqueous root extract of Morinda citrifolia. UV-vis spectroscopy, XRD, FTIR, FE
      SEM, EDX and TEM were performed to characterize the formation of gold
      nanoparticles. The synthesized gold nanoparticles were characterized by a peak at
      540 nm in the UV-vis spectrum. The XRD peaks at 38 degrees , 44 degrees , 64
      degrees  and 77 degrees  can be indexed to the (111), (200), (220) and (311)
      Bragg's reflections of cubic structure of metallic gold, respectively. The FTIR
      result showed that extract containing protein might be responsible for the
      formation of the nanoparticles and may play an important role in the
      stabilization of the formed nanoparticles. FESEM images revealed that the
      particles were triangle and mostly spherical in shape. TEM images clearly
      revealed the size of the nanoparticles were 12.17-38.26 nm in size.

PMID- 24036302
TI  - Cysteamine CdS quantum dots decorated with Fe3+ as a fluorescence sensor for the
      detection of PPi.
AB  - A new sensitive and selective fluorescence sensor for the detection of
      pyrophosphate (PPi) in aqueous media based on the Fe(3+) decorated cysteamine CdS
      QDs ([Cys-CdS QDs]-Fe(3+)) was proposed. The presence of PPi can induce the
      fluorescence quenching of [Cys-CdS QDs]-Fe(3+) due to the high formation
      constants between the phosphate group and Fe(3+). Because the complex between
      Fe(3+) and PPi acts as an efficient quencher, the concentration of PPi can be
      evaluated by tracking the degree of fluorescence quenching. The fabricated sensor
      was optimized to obtain the best sensor selectivity and sensitivity. Under
      optimal conditions, a linear relationship between the fluorescence response and
      the concentration of PPi was established in the range of 0.5-10 MUM. The limits
      of detection and quantitation for PPi were found to be 0.11 and 2.78 MUM,
      respectively. Furthermore, the proposed sensor exhibited high selectivity toward
      PPi relative to other common anions. The proposed sensor was successfully applied
      to the detection of PPi in urine samples with satisfactory results.

PMID- 24036303
TI  - Synthesis, growth, structural, optical and thermal properties of an organic
      single crystal: 4-nitroaniline 4-aminobenzoic acid.
AB  - The organic single crystals of 4-nitroaniline 4-aminobenzoic acid (4NAABA) were
      grown from ethanol solvent. The lattice parameters of the grown crystal have been
      confirmed from single crystal XRD analysis. The powder XRD pattern shows the
      various planes of grown crystal. The FTIR and (1)H NMR spectral analysis confirm
      the presence of various functional groups and the placement of proton in 4NAABA
      compound respectively. The UV absorption was carried out which shows the cutoff
      wavelength around 459 nm. The optical band gap of the crystal has been evaluated
      from the transmission spectra and absorption coefficient by extrapolation
      technique. In addition, a fluorescence spectral analysis is carried out for
      4NAABA crystals. The thermal properties of crystals were evaluated from
      thermogravimetrical analysis. It shows that the grown crystal is stable up to 160
      degrees C and the crystal has sharp melting point at 151 degrees C.

PMID- 24036304
TI  - Ribosomal DNA nanoprobes studied by Fourier transform infrared spectroscopy.
AB  - Paracoccidioides brasiliensis (P. brasiliensis) is a thermo-dimorphic fungus that
      causes paracoccidioidomycosis. Brazil epidemiological data shows that endemic
      areas are the subtropical regions, especially where agricultural activities
      predominate such as the Southeast, South, and Midwest. There are several tests to
      diagnose paracoccidioidomycosis, but they have many limitations such as low
      sensitivity, high cost, and a cross-reacting problem. In this work, gold
      nanoprobes were used to identify P. brasiliensis as an alternative diagnostic
      technique, which is easier to apply, costs less, and has great potential for
      application. The specific Ribosomal sequence of P. brasiliensis DNA was amplified
      and used to design the nanoprobes using a thiol-modified oligonucleotide. The
      results of positive and negative tests were done by UV-visible and Fourier
      Transform Infrared (FT-IR) measurements. The deconvolution of FT-IR sample
      spectra showed differences in the vibrational modes from the hydrogen bridge NHN
      and NHO bands that form the double helix DNA for samples matching the DNA
      sequence of nanoprobes that could be used to classify the samples. 

PMID- 24036305
TI  - A new chemiluminescence method for determination of clonazepam and diazepam based
      on 1-Ethyl-3-Methylimidazolium Ethylsulfate/copper as catalyst.
AB  - A novel chemiluminescence (CL) reaction, Benzodiazepines-H2O2-1-Ethyl-3
      Methylimidazolium Ethylsulfate/copper, for determination of clonazepam and
      diazepam at nanogram per milliliter level in batch-type system have been
      described. The method relies on the catalytic effect of 1-Ethyl-3
      Methylimidazolium Ethylsulfate/copper on the chemiluminescence reaction of
      Benzodiazepines, the oxidation of Benzodiazepines with hydrogen peroxide in
      natural medium. The influences of various experimental parameters such as
      solution pH, the ratio of 1-Ethyl-3 Methylimidazolium ethylsulfate concentration
      to copper ion, the type of buffer and the concentration of CL reagents were
      investigated. Under the optimum condition, the proposed method was satisfactorily
      applied for the determination of these drugs in tablets and urine without the
      interference of their potential impurities. 

PMID- 24036306
TI  - Raman investigations of Upper Cretaceous phosphorite and black shale from Safaga
      District, Red Sea, Egypt.
AB  - The mineral composition of the Upper Cretaceous Duwi phosphorite deposits and
      underlying Quseir Variegated Shale from Safaga district, Red Sea Range, Egypt,
      was investigated by dispersive and Fourier transformed Raman spectroscopy. The
      only phosphorous containing mineral detected in the phosphorite deposits was
      carbonate fluorapatite. Often carbonate fluorapatite appears associated with
      calcium sulfate and seldom with calcium carbonate in the investigated samples.
      Iron is present in the form of goethite and pyrite in the phosphorite layer,
      while pyrite, marcasite and hematite were identified in the Quseir Shale samples.
      Also, a high amount of disordered carbon was detected in the black shale layers.
      The Raman results confirm the hypothesis that the formation of the phosphorites
      took place in a marine environment. During the formation of black shale, the
      redox conditions changed, with the pH reaching values of 4 or even lower.
      Diagenetic and weathering transformations had taken place in the phosphorite
      deposits, calcium sulfate and goethite being products of these types of
      processes. 

PMID- 24036307
TI  - Spectroscopic analysis and molecular modeling on the interaction of jatrorrhizine
      with human serum albumin (HSA).
AB  - In this work, the interaction of jatrorrhizine with human serum albumin (HSA) was
      studied by means of UV-vis and fluorescence spectra. The intrinsic fluorescence
      of HSA was quenched by jatrorrhizine, which was rationalized in terms of the
      static quenching mechanism. The results show that jatrorrhizine can obviously
      bind to HSA molecules. According to fluorescence quenching calculations, the
      bimolecular quenching constant (kq), apparent quenching constant (KSV) at
      different temperatures were obtained. The binding constants K are 4059 L mol(-1)
      and 1438 L mol(-1) at 299 K and 304 K respectively, and the number of binding
      sites n is almost 1. The thermodynamic parameters determined by the Van't Hoff
      analysis of the binding constants (DeltaH -12.25 kJ mol(-1) and DeltaS 28.17 J
      mol(-1) K(-1)) clearly indicate that the electrostatic force plays a major role
      in the process. The efficiency of energy transfer and the distance between the
      donor (HSA) and the acceptor (jatrorrhizine) were calculated as 22.2% and 3.19 nm
      according to Foster's non-radiative energy transfer theory. In addition,
      synchronous fluorescence spectroscopy reveals that jatrorrhizine can influence
      HSA's microstructure. That is, jatrorrhizine is more vicinal to tryptophane (Trp)
      residue than to tyrosine (Tyr) residue and the damage site is also mainly at Trp
      residue. Molecular modeling result shows that jatrorrhizine-HSA complex formed
      not only on the basis of electrostatic forces, but also on the basis of pi-pi
      staking and hydrogen bond. The research results will offer a reference for the
      studies on the biological effects and action mechanism of small molecule with
      protein.

PMID- 24036308
TI  - Synthesis, characterization and DFT calculation of 4-fluorophenyl substituted
      tris(8-hydroxyquinoline)aluminum(III) complexes.
AB  - New 4-fluorophenyl substituted 8-hydroxyquinoline derivatives, 5-(4
      fluorophenyl)quinolin-8-ol and 5,7-bis(4-fluorophenyl)quinolin-8-ol, were
      synthesized and characterized by spectroscopic methods. The aluminum complexes of
      5-(4-fluorophenyl)quinolin-8-ol (AlQF) and of 5,7-bis(4-fluorophenyl)quinolin-8
      ol (AlQF2) exhibit strong fluorescence emission centered at 525 nm and 530 nm
      respectively. The quantum yield of both complexes were enhanced compared to the
      parent tris(8-hydroxyquinolinato)aluminum(III) complex. Electronic structures and
      photophysical properties of the new complexes were investigated theoretically by
      ab initio and density functional theory (DFT) and time dependent DFT (TD-DFT).
      Geometries of the ground state (S0) and the first excited state (S1) of the new
      complexes were optimized at the B3LYP/6-31G(d) functional and configuration
      interaction singles (CIS) method respectively. The aryl substituents were found
      to contribute significantly to the frontier molecular orbitals (FMOs). We have
      observed that in both cases the lowest occupied molecular orbital (LUMO) energy
      decreases while the energy of the highest occupied molecular orbital is slightly
      increased. The most significant increase was observed for AlQF2.

PMID- 24036310
TI  - Post-transcriptional mechanisms contribute to Etv2 repression during vascular
      development.
AB  - etv2 is an endothelial-specific ETS transcription factor that is essential for
      vascular differentiation and morphogenesis in vertebrates. While recent data
      suggest that Etv2 is dynamically regulated during vascular development, little is
      known about the mechanisms involved in this process. Here, we find that etv2
      transcript and protein expression are highly dynamic during zebrafish vascular
      development, with both apparent during early somitogenesis and subsequently down
      regulated as development proceeds. Inducible knockdown of Etv2 in zebrafish
      embryos prior to mid-somitogenesis stages, but not later, caused severe vascular
      defects, suggesting a specific role in early commitment of lateral mesoderm to
      the endothelial linage. Accordingly, Etv2-overexpressing cells showed an enhanced
      ability to commit to endothelial lineages in mosaic embryos. We further find that
      the etv2 3' untranslated region (UTR) is capable of repressing an endothelial
      autonomous transgene and contains binding sites for members of the let-7 family
      of microRNAs. Ectopic expression of let-7a could repress the etv2 3'UTR in sensor
      assays and was also able to block endogenous Etv2 protein expression, leading to
      concomitant reduction of endothelial genes. Finally, we observed that Etv2
      protein levels persisted in maternal-zygotic dicer1 mutant embryos, suggesting
      that microRNAs contribute to its repression during vascular development. Taken
      together, our results suggest that etv2 acts during early development to specify
      endothelial lineages and is then down-regulated, in part through post
      transcriptional repression by microRNAs, to allow normal vascular development.

PMID- 24036312
TI  - RAC1 regulates actin arrays during polarity establishment in the brown alga,
      Silvetia compressa.
AB  - Multicellular development has evolved independently on numerous occasions and
      there is great interest in the developmental mechanisms utilized by each of the
      divergent lineages. Fucoid algae, in the stramenopile lineage (distinct from
      metazoans, fungi and green plants) have long been used as a model for early
      development based on unique life cycle characteristics. The initially symmetric
      fucoid zygote generates a developmental axis that determines not only the site of
      growth, but also the orientation of the first cell division, whose products have
      distinct developmental fates. Establishment and maintenance of this growth axis
      is dependent on formation of a filamentous actin array that directs vesicular
      movement, depositing new membrane and wall material for development of the
      rhizoid. What is not well known, is how formation and placement of the actin
      array is regulated in fucoid algae. A candidate for this function is Rac1, a
      small GTPase of the highly conserved Rho family, which has been implicated in
      controlling the formation of actin arrays in diverse eukaryotes. We demonstrate
      that Rac1 is not only present during formation of the filamentous actin array,
      but that its localization overlaps with the array in polarizing zygotes.
      Pharmacologically inhibiting Rac1 activity was shown to impede formation and
      maintenance of the actin array, and ultimately polar growth. Evidence is provided
      that a requirement of Rac1 function is its ability to associate with membranes
      via a post-translationally added lipid tail. Taken together, the data indicate
      that Rac1 is a necessary participant in establishment of the growth pole,
      presumably by regulating the placement and formation of the actin array. A role
      for Rac1 and related proteins in regulating actin is shared by animals, plants,
      fungi and with this work, brown algae, thus a conserved mechanism for generating
      polarity is in operation in unique eukaryotic lineages. 

PMID- 24036311
TI  - CTR9/PAF1c regulates molecular lineage identity, histone H3K36 trimethylation and
      genomic imprinting during preimplantation development.
AB  - Genome-wide epigenetic reprogramming is required for successful preimplantation
      development. Inappropriate or deficient chromatin regulation can result in
      defective lineage specification and loss of genomic imprinting, compromising
      normal development. Here we report that two members of the RNA polymerase II
      associated factor, homolog (Saccharomyces cerevisiae) complex (PAF1 complex)
      components, Ctr9 and Rtf1, are required during mammalian preimplantation
      development. We demonstrate that Ctr9-deficient embryos fail to correctly specify
      lineages at the blastocyst stage. Expression of some lineage specific factors is
      markedly reduced in Ctr9 knockdown embryos, including Eomes, Elf5 and Sox2, while
      others are inappropriately expressed (Oct4, Nanog, Gata6, Fgf4 and Sox17). We
      also show that several imprinted genes (Mest, Peg3, Snrpn and Meg3) are
      aberrantly expressed although allele specific DNA methylation is not altered. We
      document a loss of histone H3 lysine 36 trimethylation (H3K36me3) in Ctr9
      deficient embryos and confirm that knockdown of either Setd2 or Rtf1 results in
      similar phenotypes. These findings show that the PAF1 complex is required for
      mammalian development, likely through regulation of H3K36me3, and indicate
      functional conservation of the PAF1 complex from yeast to mammals in vivo. 

PMID- 24036309
TI  - Disruption of mitotic arrest precedes precocious differentiation and
      transdifferentiation of pregranulosa cells in the perinatal Wnt4 mutant ovary.
AB  - Mammalian sex determination is controlled by antagonistic pathways that are
      initially co-expressed in the bipotential gonad and subsequently become male- or
      female-specific. In XY gonads, testis development is initiated by upregulation of
      Sox9 by SRY in pre-Sertoli cells. Disruption of either gene leads to complete
      male-to-female sex reversal. Ovarian development is dependent on canonical Wnt
      signaling through Wnt4, Rspo1 and beta-catenin. However, only a partial female-to
      male sex reversal results from disruption of these ovary-promoting genes. In Wnt4
      and Rspo1 mutants, there is evidence of pregranulosa cell-to-Sertoli cell
      transdifferentiation near birth, following a severe decline in germ cells. It is
      currently unclear why primary sex reversal does not occur at the sex-determining
      stage, but instead occurs near birth in these mutants. Here we show that Wnt4
      null and Rspo1-null pregranulosa cells transition through a differentiated
      granulosa cell state prior to transdifferentiating towards a Sertoli cell fate.
      This transition is preceded by a wave of germ cell death that is closely
      associated with the disruption of pregranulosa cell quiescence. Our results
      suggest that maintenance of mitotic arrest in pregranulosa cells may preclude
      upregulation of Sox9 in cases where female sex-determining genes are disrupted.
      This may explain the lack of complete sex reversal in such mutants at the sex
      determining stage. 

PMID- 24036314
TI  - Replication and validation of cryo-EM structures.

PMID- 24036313
TI  - Design and synthesis of 2alpha-(tetrazolylethyl)-1alpha,25-dihydroxyvitamin D3 as
      a high affinity ligand for vitamin D receptor.
AB  - X-ray cocrystallographic studies of the human vitamin D receptor (hVDR)-[2alpha
      (3-hydroxypropyl)-1alpha,25-dihydroxyvitamin D3 (O1C3)] complex showed that the
      terminal hydroxy group of the 2alpha-functional group of O1C3 formed a hydrogen
      bond with Arg274 in the ligand binding domain (LBD) of hVDR to stabilize the
      complex; therefore, O1C3 showed 3-times greater binding affinity for VDR than the
      natural hormone. Here, the effects of a heteroaromatic ring on binding to hVDR
      instead of the terminal OH group of O1C3 and also on preliminary biological
      activities were studied. We synthesized 2alpha-[2-(tetrazol-2-yl)ethyl]
      1alpha,25(OH)2D3 (1a) and its regioisomer 2alpha-[2-(tetrazol-1-yl)ethyl]
      1alpha,25(OH)2D3 (1b), in which 1a showed much higher hVDR binding affinity and
      greater osteocalcin promoter transactivation activity in human osteosarcoma (HOS)
      cells than those of 1b. X-ray cocrystallographic analysis of the hVDR-1a complex
      showed new hydrogen bond formation between one of the nitrogen atoms of the
      tetrazole ring and Arg274. This article is part of a Special Issue entitled '16th
      Vitamin D Workshop'. 

PMID- 24036316
TI  - Revisiting exposure: fatal and non-fatal traffic injury risk across different
      populations of travelers in Wisconsin, 2001-2009.
AB  - Comparing the injury risk of different travel modes requires using a travel-based
      measure of exposure. In this study we quantify injury risk by travel mode, age,
      race/ethnicity, sex, and injury severity using three different travel-based
      exposure measures (person-trips, person-minutes of travel, and person-miles of
      travel) to learn how these metrics affect the characterization of risk across
      populations. We used a linked database of hospital and police records to identify
      non-fatal injuries (2001-2009), the Fatality Analysis Reporting System for
      fatalities (2001-2009), and the 2001 Wisconsin Add-On to the National Household
      Travel Survey for exposure measures. In Wisconsin, bicyclists and pedestrians
      have a moderately higher injury risk compared to motor vehicle occupants
      (adjusting for demographic factors), but the risk is much higher when exposure is
      measured in distance. Although the analysis did not control for socio-economic
      status (a likely confounder) it showed that American Indian and Black travelers
      in Wisconsin face higher transportation injury risk than White travelers
      (adjusting for sex and travel mode), across all three measures of exposure.
      Working with multiple metrics to form comprehensive injury risk profiles such as
      this one can inform decision making about how to prioritize investments in
      transportation injury prevention. 

PMID- 24036315
TI  - Impact of road traffic injuries on disability rates and long-term care costs in
      Spain.
AB  - Road traffic injuries are one of the leading causes of increasing disability
      adjusted life expectancy. We analyze long-term care needs associated with motor
      vehicle crash-related disability in Spain and conclude that needs attributable
      traffic injuries are most prevalent during victims' mid-life years, they create a
      significant burden for both families and society as a whole given that public
      welfare programmes supporting these victims need to be maintained over a long
      time frame. High socio-economic costs of road traffic accidents (in Spain 0.04%
      of the GDP in 2008) are clearly indicative of the need for governments and
      policymakers to strengthen road accident preventive measures. 

PMID- 24036317
TI  - alpha-Synuclein A30P decreases neurodegeneration and increases synaptic vesicle
      release probability in CSPalpha-null mice.
AB  - alpha-Synuclein and Cysteine-string protein-alpha (CSPalpha) are presynaptic
      proteins that participate in the maintenance of synaptic function. Mutations or
      overexpression of the wild type form of alpha-synuclein have been related to
      Parkinson's disease, and CSPalpha mutations cause one type of neuronal ceroid
      lipofuscinosis. Both are adult-onset neurodegenerative diseases characterized by
      neuronal protein aggregations. Strikingly, while in mouse the lack of CSPalpha
      produces defective neurotransmission and neurodegeneration of motor terminals,
      blindness and early lethality, the moderate overexpression of wild-type alpha
      synuclein fully rescues the CSPalpha-null phenotype. Contrarily, the
      overexpression of the mutated human alpha-synuclein A30P (alpha-synuclein(hA30P))
      has much less effect in CSPalpha KO mice. To explore how the A30P mutation
      affects the neuroprotective function of alpha-synuclein we investigated synaptic
      structure and neurotransmission in motor nerve terminals of wild-type and
      CSPalpha-null mice transgenic for alpha-synuclein(hA30P). We found that although
      alpha-synuclein(hA30P) did not fully prevent neurodegeneration, it significantly
      improved synaptic organization and function in CSPalpha-null mice by enhancing
      quantal content, release probability, synaptic vesicle content, active zone
      number, postsynaptic area, and microtubule appearance. These results demonstrate
      that alpha-synuclein(hA30P) is able to ameliorate synapse degeneration, despite
      its apparent lack of functionality and its long-term pathogenic effects in
      neurons. These findings may help to understand better the dual function of alpha
      synuclein regarding neurodegeneration. This article is part of the Special Issue
      entitled 'The Synaptic Basis of Neurodegenerative Disorders'. 

PMID- 24036318
TI  - Leukocyte mitochondrial DNA copy number in bipolar disorder.
AB  - BACKGROUND: Evidence supports the role for mitochondrial impairment in the
      pathophysiology of bipolar disorder (BD). BD has been associated with decreased
      mitochondrial electron transport chain activity and increased oxidative stress.
      Also, mitochondrial DNA (mtDNA) encodes mitochondrial electron transport chain
      proteins and has been associated with altered oxidative stress. Preclinical
      studies showed that lithium treatment increased mtDNA content, but no study has
      directly assessed mtDNA content in subjects with BD in vivo. Also, the effects of
      lithium treatment on mtDNA content have never been evaluated in humans. METHODS:
      Leukocyte mtDNA content using real time-PCR was evaluated in subjects with BD
      (n=23) in a depressive episode (>=18 in the 21-item Hamilton Depression Rating
      Scale) before and after 6-week lithium treatment versus healthy controls (n=24).
      RESULTS: mtDNA content showed no significant difference between subjects with BD
      at baseline and controls (p=0.46); also no difference was observed when comparing
      before and after lithium treatment. A trend for decreased mtDNA content was
      specifically observed in BD type I compared to controls and BD type II (p=0.05).
      Importantly, endpoint mtDNA copy number was significantly correlated with age.
      CONCLUSION: In BD subjects who were younger, unmedicated and had a shorter
      duration of illness, no change was observed in mtDNA copy number. More studies
      with larger samples are warranted to evaluate mtDNA content changes in BD and its
      potential role as a treatment target, especially in BD type I and its association
      with aging.

PMID- 24036320
TI  - Prevalence and characterization of Cryptosporidium spp. in dairy cattle in Nile
      River delta provinces, Egypt.
AB  - Molecular characterizations of Cryptosporidium spp. in dairy cattle in
      industrialized nations have mostly shown a dominance of Cryptosporidium parvum,
      especially its IIa subtypes in pre-weaned calves. Few studies, however, have been
      conducted on the distribution of Cryptosporidium species and C. parvum subtypes
      in various age groups of dairy cattle in developing countries. In this study, we
      examined the prevalence and molecular characteristics of Cryptosporidium in dairy
      cattle in four Nile River delta provinces in Egypt. Modified Ziehl-Neelsen acid
      fast microscopy was used to screen for Cryptosporidium oocysts in 1974 fecal
      specimens from animals of different ages on 12 farms. Positive fecal specimens
      were identified from all studied farms with an overall prevalence of 13.6%. By
      age group, the infection rates were 12.5% in pre-weaned calves, 10.4% in post
      weaned calves, 22.1% in heifers, and 10.7% in adults. PCR-RFLP and DNA sequence
      analyses of microscopy-positive fecal specimens revealed the presence of four
      major Cryptosporidium species. In pre-weaned calves, C. parvum was most common
      (30/69 or 43.5%), but Cryptosporidium ryanae (13/69 or 18.8%), Cryptosporidium
      bovis (7/69 or 10.2%), and Cryptosporidium andersoni (7/69 or 10.2%) were also
      present at much higher frequencies seen in most industrialized nations. Mixed
      infections were seen in 12/69 (17.4%) of genotyped specimens. In contrast, C.
      andersoni was the dominant species (193/195 or 99.0%) in post-weaned calves and
      older animals. Subtyping of C. parvum based on sequence analysis of the 60kDa
      glycoprotein gene showed the presence of subtypes IIdA20G1 in nine specimens,
      IIaA15G1R1 in 27 specimens, and a rare subtype IIaA14G1R1r1b in one specimen. The
      common occurrence of non-C. parvum species and IId subtypes in pre-weaned calves
      is a distinct feature of cryptosporidiosis transmission in dairy cattle in Egypt.
      The finding of the same two dominant IIa and IId C. parvum subtypes recently
      found in humans in Egypt suggests calves can be potential reservoirs of zoonotic
      cryptosporidiosis. 

PMID- 24036319
TI  - Correspondence of executive function related functional and anatomical
      alterations in aging brain.
AB  - Neurocognitive aging studies have focused on age-related changes in neural
      activity or neural structure but few studies have focused on relationships
      between the two. The present study quantitatively reviewed 24 studies of age
      related changes in fMRI activation across a broad spectrum of executive function
      tasks using activation likelihood estimation (ALE) and 22 separate studies of age
      related changes in gray matter using voxel-based morphometry (VBM). Conjunction
      analyses between functional and structural alteration maps were constructed.
      Overlaps were only observed in the conjunction of dorsolateral prefrontal cortex
      (DLPFC) gray matter reduction and functional hyperactivation but not
      hypoactivation. It was not evident that the conjunctions between gray matter and
      activation were related to task performance. Theoretical implications of these
      results are discussed. 

PMID- 24036321
TI  - A new set of primers directed to 18S rRNA gene for molecular identification of
      Cryptosporidium spp. and their performance in the detection and differentiation
      of oocysts shed by synanthropic rodents.
AB  - Cryptosporidium spp. are cosmopolitan protozoa that infect fishes, reptiles,
      amphibians, birds and mammals. More than 20 species are recognized within this
      genus. Rodents are a group of abundant and ubiquitous organisms that have been
      considered reservoirs of Cryptosporidium for humans and livestock. The aim of
      this study was to design specific primers for the gene encoding 18S rRNA,
      potentially capable of amplifying any species or genotype of Cryptosporidium spp.
      and evaluate the diagnostic attributes of the nested-PCR based on such probes.
      The primers were designed to amplify the shortest segment as possible to maximize
      the sensitivity of the test, but preserving the discriminatory potential of the
      amplified sequences for phylogenetic inferences. The nested-PCR standardized in
      this study (nPCR-SH) was compared in terms of sensitivity with another similar
      assay (nPCR-XIAO) that has been largely used for the detection and identification
      of Cryptosporidium spp. worldwide. We also aimed to molecularly characterize
      samples of Cryptosporidum spp. isolated from synanthropic rodents using these
      probes. Forty-five rodents were captured in urban areas of the municipality of
      Umuarama, Parana State, Brazil. Fecal samples were submitted to three molecular
      tests (nested-PCRs), two of them targeted to the 18S rDNA gene (nPCR-SH and nPCR
      XIAO) and the third targeted to the gene encoding actin (nPCR-actin). The nPCR-SH
      was tested positive on samples of Cryptosporidum parvum, Cryptosporidum
      andersoni, Cryptosporidum meleagridis, Cryptosporidum hominis, Cryptosporidum
      canis, and Cryptosporidum serpentis. Sixteen samples of rodents were positive by
      nPCR-SH, six by nPCR-XIAO and five by nPCR-actin. Sequencing of amplified
      fragments allowed the identification of Cryptosporidum muris in three samples of
      Rattus rattus, and two genotypes of Cryptosporidium, the genotypes mouse II and
      III. Cryptosporidium genotype mouse II was found in one sample of Mus musculus
      and genotype mouse III, in twelve samples, being five from R. rattus and seven
      from M. musculus. The results of this study demonstrated that the primers
      designed for detection of Cryptosporidium spp. were more efficient than those
      used in the nPCR-XIAO. Genotypes or species of Cryptosporidium that can be
      usually transmitted for human beings and livestock were not found in synanthropic
      rodents, suggesting that the importance of these animals in zoonotic transmission
      of cryptosporidiosis should be revisited. 

PMID- 24036322
TI  - Changes in Heligmosomoides polygyrus glycoprotein pattern by saponins impact the
      BALB/c mice immune response.
AB  - Saponins of marigold (Calendula officinalis), in particular derivatives of 3-O
      monoglucuronide of oleanolic acid, are able to reduce infectivity of
      Heligmosomoides polygyrus in mice. The purpose of this study was to understand
      the immune activation provoked by third-stage larvae exposed to marigold
      glucuronides. We also examined the pattern of glycosylation of larval antigens
      which appeared to be crucial for induction of cytokine production in BALB/c mice;
      higher concentrations of IL-6, IFN-gamma, IL-10 and TNF-alpha were observed in
      serum or intestine one week post infection. Three weeks later, in the chronic
      phase of infection, cells in culture were able to produce IL-6, IFN-gamma, TNF
      alpha and IL-17. Restimulation of cells with H. polygyrus antigen resulted in
      reduced production of IL-6, and TNF-alpha. The pattern of cytokine production co
      existed with reduced expression of terminal glucose, alpha-linked mannose, N
      acetyl-galactosamine, beta-galactose, N-acetyl-glucosamine and alpha-fucose in
      several protein bands. Galactose, as a new terminal carbohydrate residue appeared
      in 20-24kDa protein bands. The number of immunogenic epitopes in parasitic
      antigens was reduced; only three protein bands of 56, 26 and 12kDa were
      recognized by IgG1. These studies provide a model system to find the glycosylated
      molecules expressed on nematodes that improve establishment and survival and
      characterize cytokine production in mice infected with larvae exposed to saponin.
      Identification of these molecules is the first step in the recognition of key
      antigenic epitopes able to induce protective or tolerogenic immune responses. 

PMID- 24036323
TI  - Increased susceptibility to Strongyloides venezuelensis infection is related to
      the parasite load and absence of major histocompatibility complex (MHC) class II
      molecules.
AB  - In human and murine models strongyloidiasis induce a Th2 type response. In the
      current study we investigated the role of different loads of Strongyloides
      venezuelensis in the immune response raised against the parasite and the
      participation of the major histocompatibility complex (MHC) class II molecule in
      the disease outcome in face of the different parasite burden. The C57BL/6 wild
      type (WT) and MHC II(-/-) mice were individually inoculated by subcutaneous
      injection with 500 or 3000 S. venezuelensis L3. The MHC II(-/-) mice infected
      with 3000L3 were more susceptible to S. venezuelensis infection when compared
      with WT groups, in which the parasite was completely eliminated. The production
      of Th2 cytokines and specific IgG1 or IgE antibodies against parasite were
      significantly lowered in MHC II(-/-) infected mice with different larvae
      inoculums. The infection of MHC II(-/-) mice with S. venezuelensis induced slight
      inflammatory alterations in the small intestine, and these lesions were lower
      when compared with WT mice, irrespective of the parasite load utilized to infect
      animals. Finally, we concluded that MHC class II molecules are essential in the
      immune response against S. venezuelensis mainly when infection occurs with high
      parasite inoculum. 

PMID- 24036324
TI  - Ecotoxicity of artificial sweeteners and stevioside.
AB  - Produced, consumed and globally released into the environment in considerable
      quantities, artificial sweeteners have been identified as emerging pollutants.
      Studies of environmental concentrations have confirmed the widespread
      distribution of acesulfame (ACE), cyclamate (CYC), saccharin (SAC) and sucralose
      (SUC) in the water cycle at levels that are among the highest known for
      anthropogenic trace pollutants. Their ecotoxicity, however, has yet to be
      investigated at a larger scale. The present study aimed to fill this knowledge
      gap by systematically assessing the influence of ACE, CYC and SAC and
      complementing the data on SUC. Therefore we examined their toxicity towards an
      activated sewage sludge community (30min) and applying tests with green algae
      Scenedesmus vacuolatus (24h), water fleas Daphnia magna (48h) and duckweed Lemna
      minor (7d). We also examined the effects caused by the natural sweetener
      stevioside. The high No Observed Effect Concentrations (NOECs) yielded by this
      initial evaluation indicated a low hazard and risk potential towards these
      aquatic organisms. For a complete risk assessment, however, several kinds of data
      are still lacking. In this context, obligatory ecotoxicity testing and stricter
      environmental regulations regarding food additives appear to be necessary. 

PMID- 24036325
TI  - The health significance of gas- and particle-phase terpene oxidation products: a
      review.
AB  - The reactions between terpenes and ozone (or other oxidants) produce a wide
      variety of both gas- and particle-phase products. Terpenes are biogenic volatile
      organic compounds (VOCs) that are also contained in many consumer products. Ozone
      is present indoors since it infiltrates into the indoor environment and is
      emitted by some office and consumer equipment. Some of the gaseous products
      formed are irritating to biological tissues, while the condensed-phase products
      have received attention due to their contribution to ambient fine particulate
      matter (PM2.5) and its respective health significance. Despite common scientific
      questions, the indoor and ambient air research communities have tended to operate
      in isolation regarding this topic. This review critically evaluates the
      literature related to terpene oxidation products and attempts to synthesize
      results of indoor and ambient air studies to better understand the health
      significance of these materials and identify knowledge gaps. The review documents
      the results of a literature search covering terpene oxidation chemistry,
      epidemiological, toxicological, and controlled human exposure studies, as well as
      health studies focused more generically on secondary organic aerosol (SOA). The
      literature shows a clear role for gas-phase terpene oxidation products in adverse
      airway effects at high concentrations; however, whether these effects occur at
      more environmentally relevant levels is unclear. The evidence for toxicity of
      particle-phase products is less conclusive. Knowledge gaps and future research
      needs are outlined, and include the need for more consistency in study designs,
      incorporation of reaction product measurements into epidemiological studies
      conducted in both indoor and ambient settings, and more focused research on the
      toxicity of SOA, especially SOA of biogenic origin. 

PMID- 24036326
TI  - Genotoxic effect of exposure to metal(loid)s. A molecular epidemiology survey of
      populations living and working in Panasqueira mine area, Portugal.
AB  - Previous studies investigating the exposure to metal(loid)s of populations living
      in the Panasqueira mine area of central Portugal found a higher internal dose of
      elements such as arsenic, chromium, lead, manganese, molybdenum and zinc in
      exposed individuals. The aims of the present study were to evaluate the extent of
      genotoxic damage caused by environmental and occupational exposure in individuals
      previously tested for metal(loid) levels in different biological matrices, and
      the possible modulating role of genetic polymorphisms involved in metabolism and
      DNA repair. T-cell receptor mutation assay, comet assay, micronucleus (MN) test
      and chromosomal aberrations (CA) were performed in a group of 122 subjects
      working in the Panasqueira mine or living in the same region. The modifying
      effect of polymorphisms in GSTA2, GSTM1, GSTP1, GSTT1, XRCC1, APEX1, MPG, MUTYH,
      OGG1, PARP1, PARP4, ERCC1, ERCC4, and ERCC5 genes was investigated. Significant
      increases in the frequency of all biomarkers investigated were found in exposed
      groups, however those environmentally exposed were generally higher. Significant
      influences of polymorphisms were observed for GSTM1 deletion and OGG1 rs1052133
      on CA frequencies, APEX1 rs1130409 on DNA damage, ERCC1 rs3212986 on DNA damage
      and CA frequency, and ERCC4 rs1800067 on MN and CA frequencies. Our results show
      that the metal(loid) contamination in the Panasqueira mine area induced genotoxic
      damage both in individuals working in the mine or living in the area. The
      observed effects are closely associated to the internal exposure dose, and are
      more evident in susceptible genotypes. The urgent intervention of authorities is
      required to protect exposed populations. 

PMID- 24036328
TI  - Crystal structures of CbpF complexed with atropine and ipratropium reveal clues
      for the design of novel antimicrobials against Streptococcus pneumoniae.
AB  - BACKGROUND: Streptococcus pneumoniae is a major pathogen responsible of important
      diseases worldwide such as pneumonia and meningitis. An increasing resistance
      level hampers the use of currently available antibiotics to treat pneumococcal
      diseases. Consequently, it is desirable to find new targets for the development
      of novel antimicrobial drugs to treat pneumococcal infections. Surface choline
      binding proteins (CBPs) are essential in bacterial physiology and infectivity. In
      this sense, esters of bicyclic amines (EBAs) such as atropine and ipratropium
      have been previously described to act as choline analogs and effectively compete
      with teichoic acids on binding to CBPs, consequently preventing in vitro
      pneumococcal growth, altering cell morphology and reducing cell viability.
      METHODS: With the aim of gaining a deeper insight into the structural
      determinants of the strong interaction between CBPs and EBAs, the three
      dimensional structures of choline-binding protein F (CbpF), one of the most
      abundant proteins in the pneumococcal cell wall, complexed with atropine and
      ipratropium, have been obtained. RESULTS: The choline analogs bound both to the
      carboxy-terminal module, involved in cell wall binding, and, unexpectedly, also
      to the amino-terminal module, that possesses a regulatory role in pneumococcal
      autolysis. CONCLUSIONS: Analysis of the complexes confirmed the importance of the
      tropic acid moiety of the EBAs on the strength of the binding, through pi-pi
      interactions with aromatic residues in the binding site. GENERAL SIGNIFICANCE:
      These results represent the first example describing the molecular basis of the
      inhibition of CBPs by EBA molecules and pave the way for the development of new
      generations of antipneumococcal drugs.

PMID- 24036327
TI  - PPARgamma-dependent pathway in the growth-inhibitory effects of K562 cells by
      carotenoids in combination with rosiglitazone.
AB  - BACKGROUND: Carotenoids have been found to play roles in the prevention and
      therapy of some cancers which PPARgamma was also discovered to be involved in.
      The present studies were directed to determine the inhibitory effects of
      carotenoids in combination with rosiglitazone, a synthetic PPARgamma agonist, on
      K562 cell proliferation and elucidate the contribution of PPARgamma-dependent
      pathway to cell proliferation suppression. METHODS: The effects of carotenoid and
      rosiglitazone combination on K562 cell proliferation were evaluated by trypan
      blue dye exclusion assay and MTT assay. When PPARgamma has been inhibited by
      GW9662 and siRNA, cycle-related regulator expression in K562 cells treated with
      carotenoid and rosiglitazone combination was analyzed by Western blotting.
      RESULTS: Rosiglitazone inhibited K562 cell proliferation and augmented the
      inhibitory effects of carotenoids on the cell proliferation greatly. Specific
      PPARgamma inhibition attenuated the cell growth suppression induced by carotenoid
      and rosiglitazone combination. GW9662 pre-treatment attenuated the enhanced up
      regulation of PPARgamma expression caused by the combination treatment. Moreover,
      GW9662 and PPARgamma siRNA also significantly attenuated the up-regulation of p21
      and down-regulation of cyclin D1 caused by carotenoids and rosiglitazone.
      CONCLUSIONS: PPARgamma signaling pathway, via stimulating p21 and inhibiting
      cyclin D1, may play an important role in the anti-proliferative effects of
      carotenoid and rosiglitazone combination on K562 cells. GENERAL SIGNIFICANCE:
      Carotenoids in combination with rosiglitazone are hopeful to provide attractive
      dietary or supplementation-based and pharmaceutical strategies to treat cancer
      diseases.

PMID- 24036329
TI  - 1.55A-resolution structure of ent-copalyl diphosphate synthase and exploration of
      general acid function by site-directed mutagenesis.
AB  - BACKGROUND: The diterpene cyclase ent-copalyl diphosphate synthase (CPS)
      catalyzes the first committed step in the biosynthesis of gibberellins. The
      previously reported 2.25A resolution crystal structure of CPS complexed with (S)
      15-aza-14,15-dihydrogeranylgeranyl thiolodiphosphate (1) established the
      alphabetagamma domain architecture, but ambiguities regarding substrate analog
      binding remained. METHOD: Use of crystallization additives yielded CPS crystals
      diffracting to 1.55A resolution. Additionally, active site residues that hydrogen
      bond with D379, either directly or through hydrogen bonded water molecules, were
      probed by mutagenesis. RESULTS: This work clarifies structure-function
      relationships that were ambiguous in the lower resolution structure. Well-defined
      positions for the diphosphate group and tertiary ammonium cation of 1, as well as
      extensive solvent structure, are observed. CONCLUSIONS: Two channels involving
      hydrogen bonded solvent and protein residues lead to the active site, forming
      hydrogen bonded "proton wires" that link general acid D379 with bulk solvent.
      These proton wires may facilitate proton transfer with the general acid during
      catalysis. Activity measurements made with mutant enzymes indicate that N425,
      which donates a hydrogen bond directly to D379, and T421, which hydrogen bonds
      with D379 through an intervening solvent molecule, help orient D379 for
      catalysis. Residues involved in hydrogen bonds with the proton wire, R340 and
      D503, are also important. Finally, conserved residue E211, which is located near
      the diphosphate group of 1, is proposed to be a ligand to Mg(2+) required for
      optimal catalytic activity. GENERAL SIGNIFICANCE: This work establishes structure
      function relationships for class II terpenoid cyclases.

PMID- 24036330
TI  - Comparative transcriptional analysis reveals distinct expression patterns of
      channel catfish genes after the first infection and re-infection with Aeromonas
      hydrophila.
AB  - To determine whether transcriptional levels of channel catfish (Ictalurus
      punctatus) genes are differentially regulated between a first infection with
      Aeromonas hydrophila and a re-infection, suppression subtractive hybridization
      (SSH) was performed in this study using anterior kidney cDNA after the re
      infection as tester. Of the 96 clones isolated from the SSH library, 28 unique
      expressed sequence tags (ESTs) were obtained, of which eight were confirmed to be
      slightly but significantly (P < 0.05) more up-regulated by the re-infection at 6
      h post infection (hpi). Expression kinetics studies at 3, 6, 12, 24, and 48 hpi
      revealed that the eight ESTs were significantly (P = 0.016) more up-regulated by
      the first infection, with a major peak at 3 hpi. A total of 96 genes reported in
      literature to be up-regulated by bacterial infections were selected and subjected
      to expression analysis at 3 hpi. Of the 96 selected genes, 19 were found to be
      significantly (P < 0.05) induced by A. hydrophila after the first infection and
      the re-infection. The 19 genes belonged to the following five main categories: 1)
      toll-like receptor (TLR2, TLR3, TLR5, TLR21); 2) antimicrobial peptide (NK-lysin
      type 1, NK-lysin type 2, NK-lysin type 3, cathepsin D, transferrin, hepcidin); 3)
      cytokine or chemokine (interleukin-1beta, interleukin-10, tumor necrosis factor
      alpha, chemokine CXCL-10); 4) signaling proteins (cadherin EGF LAG seven-pass G
      type receptor 1, very large inducible GTPase 1, arginine deiminase type 2,
      lymphokine-activated killer T-cell originated protein kinase); 5) lysozyme
      (lysozyme c). Overall, the total 27 genes (8 ESTs plus the 19 selected genes)
      were significantly (P < 0.001) more induced by the first infection. Peaked
      expression of lysozyme c and serum lysozyme activity after the first infection
      were seen at 24 hpi, whereas that after the re-infection were seen at 12 hpi,
      suggesting that both innate and adaptive immunity were involved in the defense
      against the re-infection of A. hydrophila.

PMID- 24036331
TI  - Identification and cloning of the second type transglutaminase from Litopenaeus
      vannamei, and its transcription following pathogen infection and in relation to
      the haemolymph coagulation.
AB  - Complementary (c)DNA encoding transglutaminaseII (TGII) messenger (m)RNA of white
      shrimp, Litopenaeus vannamei, was cloned from haemocytes by a reverse
      transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA
      ends (RACE) using oligonucleotide primers based on the TG sequence of the
      horseshoe crab, Tachypleus tridentatus (accession no.: BAA02134), tiger shrimp,
      Penaeus monodon (AAV49005; AAO33455), kuruma shrimp, Marsupenaeus japonicus
      (BAD36808) and Pacifastacus leniusculus (AAK69205) TG. The 2405-bp cDNA contained
      an open reading frame (ORF) of 2292 bp, a 31-bp 5'-untranslated region (UTR), and
      an 82-bp 3'-UTR containing a poly A tail. The molecular mass of the deduced amino
      acid (aa) sequence (764 aa) was 85.9 kDa with an estimated pI of 5.32. The L.
      vannamei TGII (abbreviated LvTGII) contains a typical TG-like homologue, two
      putative integrin binding motif (RGD and KGD), and five calcium-binding sites;
      three catalytic triad is present as in arthropod TG. Sequence comparison and
      phylogenetic analysis revealed that shrimp TG can be separated into two groups,
      STGI and STGII, and LvTGII is more closely related to STGII than to STGI. LvTGII
      mRNA was detected in all tested tissues of L. vannamei, and was highly expressed
      in haemocytes. The haemocytes of L. vannamei injected with Vibrio alginolyticus
      showed a significant increase of LvTGI and LvTGII mRNA expression at 6 h followed
      by a notable decrease at 24 h in LvTGI and a continually increase in LvTGII
      indicating a complementary effect, which implied that both LvTGs involved in the
      immune response of shrimp, and LvTGII was more important in the later defense
      response. The gene silencing of LvTGII in shrimp significantly decreased LvTGII
      expression and TG activity of haemocytes, and significantly increased clotting
      time of haemolymph, suggests that the cloned LvTGII is a clotting enzyme involved
      in haemolymph coagulation of L. vannamei. In conclusion, the cloned LvTGII is a
      clotting enzyme involved in coagulation of haemolymp and immune response of white
      shrimp, L. vannamei.

PMID- 24036333
TI  - Excretory products of the cestode, Schistocephalus solidus, modulate in vitro
      responses of leukocytes from its specific host, the three-spined stickleback
      (Gasterosteus aculeatus).
AB  - Helminth parasites have evolved remarkable strategies to manipulate the immune
      system of their hosts. During infections of three-spined stickleback
      (Gasterosteus aculeatus) with the cestode Schistocephalus solidus prominent
      immunological changes occur, presumably due to manipulative activity of the
      parasite. We hypothesise that excretory/secretory products of the parasite are
      involved in the manipulation of the stickleback's immune system and that this may
      depend on the individual parasite and its origin. We therefore produced S.
      solidus conditioned cell culture media (SSCM) with parasites from different
      origins (Norway, Spain and Germany) and exposed head kidney leukocytes (HKL) from
      un-infected sticklebacks in cell cultures to SSCM. After in vitro culture, HKL
      were subjected to differential cell counts (granulocytes/lymphocytes) by means of
      flow cytometry. Leukocyte sub-populations were analysed for cell viability and
      changes in cell morphology. The respiratory burst activity was measured with a
      luminescence assay. Exposure of HKL to SSCM induced an up-regulation of
      respiratory burst activity after already 1 h, which was still elevated at 24 h,
      but which was in some cases significantly down-regulated after 96 h. Respiratory
      burst was positively correlated with the number of live granulocytes in the
      culture, suggesting that the respiratory burst activity was changed by SSCM
      effects on granulocyte viability. After 1 h and 24 h of HKL culture, no
      lymphocyte responses to SSCM were detectable, but after 96 h lymphocyte viability
      was significantly decreased with SSCM from Spanish S. solidus. In these cultures,
      residual lymphocytes increased in size, suggesting that cell death and activation
      might have occurred in parallel. The highest respiratory burst activity was
      induced by SSCM from Spanish parasites, in particular when they were grown in
      sympatric sticklebacks. The in vitro HKL responses to SSCM depended on the
      individual parasite and its population of origin, suggesting that in vivo, S.
      solidus excretory products are regulated individually, possibly to balance the
      interplay of each individual host-parasite pair.

PMID- 24036332
TI  - First report of the pituitary adenylate cyclase activating polypeptide (PACAP) in
      crustaceans: conservation of its functions as growth promoting factor and
      immunomodulator in the white shrimp Litopenaeus vannamei.
AB  - The high conservation of the pituitary adenylate cyclase activating polypeptide
      (PACAP) sequence indicates that this peptide fulfills important biological
      functions in a broad spectrum of organisms. However, in invertebrates, little is
      known about its presence and its functions remain unclear. Up to now, in non
      mammalian vertebrates, the majority of studies on PACAP have focused mainly on
      the localization, cloning and structural evolution of this peptide. As yet,
      little is known about its biological functions as growth factor and
      immunomodulator in lower vertebrates. Recently, we have shown that PACAP, apart
      from its neuroendocrine role, influences immune functions in larval and juvenile
      fish. In this work, we isolated for the first time the cDNA encoding the mature
      PACAP from a crustacean species, the white shrimp Litopenaeus vannamei,
      corroborating its high degree of sequence conservation, when compared to
      sequences reported from tunicates to mammalian vertebrates. Based on this, we
      have evaluated the effects of purified recombinant Clarias gariepinus PACAP
      administrated by immersion baths on white shrimp growth and immunity. We
      demonstrated that PACAP improves hemocyte count, superoxide dismutase, lectins
      and nitric oxide synthase derived metabolites in treated shrimp related with an
      increase in total protein concentration and growth performance. From our results,
      PACAP acts as a regulator of shrimp growth and immunity, suggesting that in
      crustaceans, as in vertebrate organisms, PACAP is an important molecule shared by
      both the endocrine and the immune systems. 

PMID- 24036334
TI  - Pathological analysis of hemolymphs of Charybdis japonica infected with Vibrio
      alginolyticus.
AB  - We explored the pathogenic mechanism of Vibrio alginolyticus in the stone crab
      Charybdis japonica by studying the hemolymph of C. japonica artificially infected
      by V. alginolyticus. To this end, Wright-Geimsa staining and electron microscopy
      were used, and phenoloxidase (PO) activity and the immune protection rate of C.
      japonica injected with immune polysaccharide during infection were analyzed. The
      results indicated that the total hemocyte and hyaline hemocyte (HH) counts in
      diseased crabs were significantly lower than those in healthy crabs (P < 0.05),
      whereas the large granule hemocytes (LGHs) were significantly higher in diseased
      crabs than in healthy crabs (P < 0.05). The cellular sizes of HHs and LGHs showed
      an increasing trend after V. alginolyticus infection, while the
      nuclear/cytoplasmic ratio (NP) of these cells showed a sharp decline after V.
      alginolyticus infection (P < 0.05). Micro-pathological analysis of hemocytes
      revealed fewer hemocytes in the hemolymph of diseased crabs and the presence of
      disintegrated cells. Ultrastructural and micro-pathological analyses showed
      damage in all types of hemocytes. The mitochondria were damaged and incomplete in
      structure, parts of the nuclear membrane were anamorphic and parts of the nuclei
      had shrunk, hematocyte nuclei exhibited heterochromatinization, hemocyte granules
      were increased in the polysaccharide-treated group infected with V.
      alginolyticus, and the numbers of mitochondria and rough endoplasmic reticulum
      were also increased. PO activity in the two Vibrio-infected groups peaked at 6 h
      and 24 h after infection, respectively, and PO activity increased in the
      hemolymph of infected crabs but sharply decreased with prolonged infection.
      Finally, the PO activities in the two Vibrio-infected groups were significantly
      lower than controls at 120 h post-infection (P < 0.05). Interestingly, PO
      activity was higher in polysaccharide-treated crabs than non-polysaccharide
      challenged infected crabs, resulting in an immunoprotective rate of 69.64% at 7
      days post-infection. This phenomenon suggests that polysaccharides could enhance
      the organism's antibacterial defenses by improving immune-related enzyme
      activity.

PMID- 24036335
TI  - The cytokine networks of adaptive immunity in fish.
AB  - Cytokines, produced at the site of entry of a pathogen, drive inflammatory
      signals that regulate the capacity of resident and newly arrived phagocytes to
      destroy the invading pathogen. They also regulate antigen presenting cells
      (APCs), and their migration to lymph nodes to initiate the adaptive immune
      response. When naive CD4+ T cells recognize a foreign antigen-derived peptide
      presented in the context of major histocompatibility complex class II on APCs,
      they undergo massive proliferation and differentiation into at least four
      different T-helper (Th) cell subsets (Th1, Th2, Th17, and induced T-regulatory
      (iTreg) cells in mammals. Each cell subset expresses a unique set of signature
      cytokines. The profile and magnitude of cytokines produced in response to
      invasion of a foreign organism or to other danger signals by activated CD4+ T
      cells themselves, and/or other cell types during the course of differentiation,
      define to a large extent whether subsequent immune responses will have beneficial
      or detrimental effects to the host. The major players of the cytokine network of
      adaptive immunity in fish are described in this review with a focus on the
      salmonid cytokine network. We highlight the molecular, and increasing cellular,
      evidence for the existence of T-helper cells in fish. Whether these cells will
      match exactly to the mammalian paradigm remains to be seen, but the early
      evidence suggests that there will be many similarities to known subsets.
      Alternative or additional Th populations may also exist in fish, perhaps
      influenced by the types of pathogen encountered by a particular species and/or
      fish group. These Th cells are crucial for eliciting disease resistance post
      vaccination, and hopefully will help resolve some of the difficulties in
      producing efficacious vaccines to certain fish diseases. 

PMID- 24036336
TI  - 1,500 years of hydrocephalus treatment--how little it has changed.

PMID- 24036337
TI  - Vasospasm in subarachnoid hemorrhage.

PMID- 24036338
TI  - Balloon test occlusion in the setting of vessel sacrifice: procedural refinements
      and adjunct assessment measures.

PMID- 24036339
TI  - Discrepancy between voluntary movement and motor-evoked potentials in evaluation
      of motor function during clipping of anterior circulation aneurysms.
AB  - BACKGROUND: Various modalities have been used to confirm the blood flow through
      parent arteries or surrounding perforating arteries during surgical aneurysm
      clipping, including motor-evoked potentials (MEPs), Doppler ultrasound, and
      indocyanine green videoangiography. Nonetheless, contralateral hemiparesis due to
      arterial blood flow insufficiency may arise because of false-positive or false
      negative errors. By performing controlled intraoperative awakening during
      aneurysm clipping, we compared patients' voluntary movements with simultaneous
      MEP. METHODS: Four patients with anterior choroidal artery aneurysms and one
      patient with a dorsal internal carotid artery aneurysm were included in this
      study. MEP and intraoperative voluntary movements under awake craniotomy were
      assessed simultaneously during and after the clipping procedure. RESULTS:
      Aneurysms were safely and successfully clipped in all patients, with no evidence
      of postoperative neurological deficits. Voluntary movements and MEP findings did
      not differ from the control state in three patients. In the other two patients,
      we observed a discrepancy between MEP amplitudes and voluntary movements. In one
      patient, deterioration and subsequent improvement in voluntary movements were
      preceded by MEP amplitude reduction during clipping. In the other patient, MEP
      amplitude did not change although voluntary movement deteriorated during
      temporary occlusion of the internal carotid artery. CONCLUSIONS: Intraoperative
      neurological assessment during aneurysmal clipping under awake craniotomy is
      feasible and safe, and should be valuable for the assessment of ischemia,
      especially in the anterior choroidal artery. From a neurophysiologic viewpoint,
      MEP may be insufficiently sensitive for evaluating voluntary movement under
      ischemia.

PMID- 24036340
TI  - Recruitment of medical students into neurosurgery: some strategies.

PMID- 24036341
TI  - The endoscope and the giant macroadenoma: a match made in heaven.

PMID- 24036342
TI  - Long-term progression of lipomatosis of nerve.
AB  - OBJECTIVE: Lipomatosis of nerve (LN) is a condition of massive peripheral nerve
      enlargement due to proliferation of fibrous and adipose tissue within the nerve,
      the natural history of which is currently unknown. We measured the pattern of
      growth in individuals with long-term radiologic follow-up. METHODS: Review of the
      searchable records for LN at our institution found 52 patients, confirmed by
      pathology or pathognomic appearance on MRI. Ten patients had serial MRI of the
      same anatomic region for more than 2 years of clinical follow-up. Volumetric
      analysis was performed using regions of interest on serially imaged segments of
      affected nerves. Adjustment for skeletal growth was performed for pediatric
      patients. RESULTS: LN enlarged in 7 of 10 individuals, often both longitudinally
      along the nerve and in cross-sectional volume. Regarding cross-sectional volume,
      2 of the 10 patients demonstrated volume growth more than doubling and 5
      additional patients had a >20% increase in nerve volume; the remaining 3 patients
      were quiescent, where change in the nerve volume was within the error range of
      volumetric analysis. All cases with growth remained >20% after adjustment for
      skeletal growth. Five of 10 individuals had longitudinal extension, even with
      correction for skeletal growth. More significant growth was noted in younger
      patients (P=0.02). Growth rates more than 5% per year correlated with surgery,
      without statistical significance in this small population (P=0.14). CONCLUSIONS:
      Serial MRI reveals progressive enlargement of LN. The rate of growth was more
      profound in youth, but also occurred in early adulthood.

PMID- 24036343
TI  - The polyketide synthase gene pks4 of Trichoderma reesei provides pigmentation and
      stress resistance.
AB  - Species of the fungal genus Trichoderma (Hypocreales, Ascomycota) are well-known
      for their production of various secondary metabolites. Nonribosomal peptides and
      polyketides represent a major portion of these products. In a recent phylogenomic
      investigation of Trichoderma polyketide synthase (PKS)-encoding genes, the pks4
      from T. reesei was shown to be an orthologue of pigment-forming PKSs involved in
      synthesis of aurofusarin and bikaverin in Fusarium spp. In this study, we show
      that deletion of this gene in T. reesei results in loss of green conidial
      pigmentation and in pigmentation alteration of teleomorph structures. It also has
      an impact on conidial cell wall stability and the antagonistic abilities of T.
      reesei against other fungi, including formation of inhibitory metabolites. In
      addition, deletion of pks4 significantly influences the expression of other PKS
      encoding genes of T. reesei. To our knowledge, this is the first indication that
      a low-molecular-weight pigment-forming PKS is involved in defense, mechanical
      stability, and stress resistance in fungi. 

PMID- 24036344
TI  - Murine models of Candida gastrointestinal colonization and dissemination.
AB  - Ninety-five percent of infectious agents enter through exposed mucosal surfaces,
      such as the respiratory and gastrointestinal (GI) tracts. The human GI tract is
      colonized with trillions of commensal microbes, including numerous Candida spp.
      Some commensal microbes in the GI tract can cause serious human infections under
      specific circumstances, typically involving changes in the gut environment and/or
      host immune conditions. Therefore, utilizing animal models of fungal GI
      colonization and dissemination can lead to significant insights into the complex
      pathophysiology of transformation from a commensal organism to a pathogen and
      host-pathogen interactions. This paper will review the methodologic approaches
      used for modeling GI colonization versus dissemination, the insights learned from
      these models, and finally, possible future directions using these animal modeling
      systems. 

PMID- 24036345
TI  - Abi is required for modulation and stability but not localization or activation
      of the SCAR/WAVE complex.
AB  - The SCAR/WAVE complex drives actin-based protrusion, cell migration, and cell
      separation during cytokinesis. However, the contribution of the individual
      complex members to the activity of the whole remains a mystery. This is primarily
      because complex members depend on one another for stability, which limits the
      scope for experimental manipulation. Several studies suggest that Abi, a
      relatively small complex member, connects signaling to SCAR/WAVE complex
      localization and activation through its polyproline C-terminal tail. We generated
      a deletion series of the Dictyostelium discoideum Abi to investigate its exact
      role in regulation of the SCAR complex and identified a minimal fragment that
      would stabilize the complex. Surprisingly, loss of either the N terminus of Abi
      or the C-terminal polyproline tail conferred no detectable defect in complex
      recruitment to the leading edge or the formation of pseudopods. A fragment
      containing approximately 20% Abi--and none of the sites that couple to known
      signaling pathways--allowed the SCAR complex to function with normal localization
      and kinetics. However, expression of N-terminal Abi deletions exacerbated the
      cytokinesis defect of the Dictyostelium abi mutant, which was earlier shown to be
      caused by the inappropriate activation of SCAR. This demonstrates, unexpectedly,
      that Abi does not mediate the SCAR complex's ability to make pseudopods, beyond
      its role in complex stability. Instead, we propose that Abi has a modulatory role
      when the SCAR complex is activated through other mechanisms.

PMID- 24036346
TI  - Dictyostelium lipid droplets host novel proteins.
AB  - Across all kingdoms of life, cells store energy in a specialized organelle, the
      lipid droplet. In general, it consists of a hydrophobic core of triglycerides and
      steryl esters surrounded by only one leaflet derived from the endoplasmic
      reticulum membrane to which a specific set of proteins is bound. We have chosen
      the unicellular organism Dictyostelium discoideum to establish kinetics of lipid
      droplet formation and degradation and to further identify the lipid constituents
      and proteins of lipid droplets. Here, we show that the lipid composition is
      similar to what is found in mammalian lipid droplets. In addition, phospholipids
      preferentially consist of mainly saturated fatty acids, whereas neutral lipids
      are enriched in unsaturated fatty acids. Among the novel protein components are
      LdpA, a protein specific to Dictyostelium, and Net4, which has strong homologies
      to mammalian DUF829/Tmem53/NET4 that was previously only known as a constituent
      of the mammalian nuclear envelope. The proteins analyzed so far appear to move
      from the endoplasmic reticulum to the lipid droplets, supporting the concept that
      lipid droplets are formed on this membrane. 

PMID- 24036347
TI  - SPO71 encodes a developmental stage-specific partner for Vps13 in Saccharomyces
      cerevisiae.
AB  - The creation of haploid gametes in yeast, termed spores, requires the de novo
      formation of membranes within the cytoplasm. These membranes, called prospore
      membranes, enclose the daughter nuclei generated by meiosis. Proper growth and
      closure of prospore membranes require the highly conserved Vps13 protein.
      Mutation of SPO71, a meiosis-specific gene first identified as defective in spore
      formation, was found to display defects in membrane morphogenesis very similar to
      those seen in vps13Delta cells. Specifically, prospore membranes are smaller than
      in the wild type, they fail to close, and membrane vesicles are present within
      the prospore membrane lumen. As in vps13Delta cells, the levels of
      phophatidylinositol-4-phosphate are reduced in the prospore membranes of
      spo71Delta cells. SPO71 is required for the translocation of Vps13 from the
      endosome to the prospore membrane, and ectopic expression of SPO71 in vegetative
      cells results in mislocalization of Vps13. Finally, the two proteins can be
      coprecipitated from sporulating cells. We propose that Spo71 is a sporulation
      specific partner for Vps13 and that they act in concert to regulate prospore
      membrane morphogenesis. 

PMID- 24036348
TI  - Up-regulation of glyoxalase 1 by mangiferin prevents diabetic nephropathy
      progression in streptozotocin-induced diabetic rats.
AB  - Advanced glycation endproducts (AGEs) and its precursor methylglyoxal are
      associated with diabetic nephropathy (DN). Mangiferin has many beneficial
      biological activities, including anti-inflammatory, anti-oxidative and anti
      diabetic effects. We investigated the effect of mangiferin on DN and its
      potential mechanism associated with glyoxalase 1 (Glo-1), a detoxifying enzyme of
      methylglyoxal, in streptozotocin-induced rat model of DN. Diabetic rats were
      treated orally with mangiferin (15, 30, and 60 mg/kg) or distilled water for 9
      weeks. Kidney tissues were collected for morphologic observation and the
      determination of associated biochemical parameters. The cultured mesangial cells
      were used to measure the activity of Glo-1 in vitro. Chronic treatment with
      mangiferin significantly ameliorated renal dysfunction in diabetic rats, as
      evidenced by decreases in albuminuria, blood urea nitrogen, kidney weight index,
      periodic acid-schiff stain positive mesangial matrix area, glomerular
      extracellular matrix expansion and accumulation, and glomerular basement membrane
      thickness. Meanwhile, mangiferin treatment caused substantial increases in the
      enzymatic activity of Glo-1 in vivo and in vitro, and protein and mRNA expression
      of Glo-1, reduced levels of AGEs and the protein and mRNA expression of their
      receptor (RAGE) in the renal cortex of diabetic rats. Moreover, mangiferin
      significantly attenuated oxidative stress damage as reflected by the lowered
      malondialdehyde and the increased glutathione levels in the kidney of diabetic
      rats. However, mangiferin did not affect the blood glucose and body weight of
      diabetic rats. Therefore, mangiferin can remarkably ameliorate DN in rats through
      inhibiting the AGEs/RAGE aix and oxidative stress damage, and Glo-1 may be a
      target for mangiferin action.

PMID- 24036349
TI  - The dual effect of PNU-120596 on alpha7 nicotinic acetylcholine receptor
      channels.
AB  - PNU-120596 (1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)urea), a
      Type-II positive allosteric modulator of alpha(7) nicotinic acetylcholine
      receptors inhibits alpha(7) desensitization and robustly prolongs openings of
      alpha(7) channels. However, these effects may render alpha(7) channels more
      accessible to positively charged molecules and thus, more susceptible to voltage
      dependent open-channel-block-like inhibition. To test this hypothesis, choline
      chloride (i.e., choline), a selective endogenous alpha(7) agonist, and
      bicuculline methochloride (i.e., bicuculline), a competitive alpha(7) antagonist,
      were used as membrane voltage-sensitive probes in whole-cell voltage-clamp
      recordings from hippocampal CA1 interneurons in acute brain slices in the absence
      and presence of PNU-120596. PNU-120596 enhanced voltage-dependent inhibition of
      alpha(7) responses by bicuculline and choline. In the presence of PNU-120596,
      alpha(7) channels favored a burst-like kinetic modality in the presence, but not
      absence of bicuculline and bursts of alpha(7) openings were voltage-dependent.
      These results suggest that PNU-120596 alters the pharmacology of alpha(7)
      channels by making these channels more susceptible to voltage-dependent
      inhibitory interactions with positively charged drugs at concentrations that do
      not potently inhibit alpha(7) channels without PNU-120596. This inhibition
      imitates alpha(7) nicotinic receptor desensitization and compromises the
      potentiating anti-desensitization effects of PNU-120596 on alpha(7) nicotinic
      receptors. This unexpected dual action of PNU-120596, and possibly other Type-II
      positive allosteric modulators of alpha(7) nicotinic receptors, may lead to
      unanticipated alpha(7) channel-drug interactions and misinterpretation of
      alpha(7) single-channel data.

PMID- 24036350
TI  - Bryostatin 5 induces apoptosis in acute monocytic leukemia cells by activating
      PUMA and caspases.
AB  - Acute leukemia is a malignant clonal hematopoietic stem cell disease. In the
      current study, we examined the effects of bryostatin 5 on acute monocytic
      leukemia cells in vitro and in vivo. We also explored the mechanisms and pathways
      underlying the increase in apoptosis induced by bryostatin 5. Bryostatin 5
      inhibited the growth of primary acute monocytic leukemia cells and U937 cells in
      a dose- and time-dependent manners. Bryostatin 5 also induced an increase in
      apoptosis and a decrease in the mitochondrial membrane potential (MMP) in U937
      cells. Transmission electron microscopy (TEM) revealed that bryostatin 5-treated
      cells displayed typical apoptotic characteristics (chromatin condensation,
      karyopyknosis and formation of crescents and apoptotic bodies). In addition,
      bryostatin 5 increased the expression of P53 upregulated modulator of apoptosis
      (PUMA) and slightly increased P53 expression. Bryostatin 5 also significantly
      decreased Bcl-XL expression and significantly increased the expression levels of
      Bak, Bax, cleaved caspase 9 and cleaved caspase 3. The pro-apoptotic activity of
      bryostatin 5 in U937 cells was inhibited by PUMA siRNA and z-LEHD-fmk (a specific
      caspase 9 inhibitor). In addition, the PUMA siRNA significantly affected the
      expression of cleaved caspase 9, whereas z-LEHD-fmk had little effect on the
      expression of PUMA. The results suggest that PUMA is located upstream of caspase
      9 in this apoptotic signaling pathway. These novel findings provide mechanistic
      insight into the induction of apoptosis by bryostatin 5 and might facilitate the
      development of clinical strategies to enhance the therapeutic efficacy of
      treatments for acute monocytic leukemia. 

PMID- 24036351
TI  - Sema4D localizes to synapses and regulates GABAergic synapse development as a
      membrane-bound molecule in the mammalian hippocampus.
AB  - While numerous recent advances have contributed to our understanding of
      excitatory synapse formation, the processes that mediate inhibitory synapse
      formation remain poorly defined. Previously, we discovered that RNAi-mediated
      knockdown of a Class 4 Semaphorin, Sema4D, led to a decrease in the density of
      inhibitory synapses without an apparent effect on excitatory synapse formation.
      Our current work has led us to new insights about the molecular mechanisms by
      which Sema4D regulates GABAergic synapse development. Specifically, we report
      that the extracellular domain of Sema4D is proteolytically cleaved from the
      surface of neurons. However, despite this cleavage event, Sema4D signals through
      its extracellular domain as a membrane-bound, synaptically localized protein
      required in the postsynaptic membrane for proper GABAergic synapse formation.
      Thus, as Sema4D is one of only a few molecules identified thus far that
      preferentially regulates GABAergic synapse formation, these findings have
      important implications for our mechanistic understanding of this process. 

PMID- 24036352
TI  - Neuroenhancement: enhancing brain and mind in health and in disease.
AB  - Humans have long used cognitive enhancement methods to expand the proficiency and
      range of the various mental activities that they engage in, including writing to
      store and retrieve information, and computers that allow them to perform myriad
      activities that are now commonplace in the internet age. Neuroenhancement
      describes the use of neuroscience-based techniques for enhancing cognitive
      function by acting directly on the human brain and nervous system, altering its
      properties to increase performance. Cognitive neuroscience has now reached the
      point where it may begin to put theory derived from years of experimentation into
      practice. This special issue includes 16 articles that employ or examine a
      variety of neuroenhancement methods currently being developed to increase
      cognition in healthy people and in patients with neurological or psychiatric
      illness. This includes transcranial electromagnetic stimulation methods, such as
      transcranial direct current stimulation (tDCS) and transcranial magnetic
      stimulation (TMS), along with deep brain stimulation, neurofeedback, behavioral
      training techniques, and these and other techniques in conjunction with
      neuroimaging. These methods can be used to improve attention, perception, memory
      and other forms of cognition in healthy individuals, leading to better
      performance in many aspects of everyday life. They may also reduce the cost,
      duration and overall impact of brain and mental illness in patients with
      neurological and psychiatric illness. Potential disadvantages of these techniques
      are also discussed. Given that the benefits of neuroenhancement outweigh the
      potential costs, these methods could potentially reduce suffering and improve
      quality of life for everyone, while further increasing our knowledge about the
      mechanisms of human cognition. 

PMID- 24036354
TI  - Tactile and visual motion direction processing in hMT+/V5.
AB  - The human motion complex hMT+/V5 is activated not only by visual motion, but also
      by tactile and auditory motion. Whilst direction-selectivity has been found
      within this complex for visual and auditory stimuli, it is unknown whether
      hMT+/V5 also contains direction-specific information from the tactile modality.
      In the current study, we sought to investigate whether hMT+/V5 contains direction
      specific information about visual/tactile moving stimuli. Leftward and rightward
      moving stimuli were presented in the visual and tactile modalities in an event
      related fMRI design. Using region-of-interest-based multivariate pattern analysis
      we could decode the two motion directions for both tactile and visual stimuli in
      hMT+/V5. The activity patterns of the two modalities differed significantly,
      indicating that motion direction information from different modalities may be
      carried by distinct sets of neuronal populations. Our findings show that hMT+/V5
      contains specific information about the direction of a moving stimulus in both
      the tactile and visual modalities, supporting the theory of hMT+/V5 being a
      multimodal motion area. 

PMID- 24036355
TI  - A case of naturally occurring visual field loss in a chimpanzee with an arachnoid
      cyst.
AB  - Deficits in the occipital cortex have varying consequences among mammalian
      species. Such variations are indicative of evolutionary transitions in the
      striate cortical contribution to visually guided behavior. However, little is
      known about the role of the striate cortex in visually guided behavior in
      chimpanzees due to ethical concerns about invasive experiments and methodological
      limitations such as the inability to monitor gaze movements. We had the
      opportunity to study the behavioral consequences of a deficit in the occipital
      cortex in a chimpanzee with a naturally occurring arachnoid cyst in her right
      occipital lobe. We assessed the chimpanzee's ability to detect a small light
      probe (0.5 visual degree, Michelson contrast > 0.9) presented at several
      locations in the visual field while monitoring gaze direction using an infra-red
      remote eye-tracker recently introduced to studies of great apes. The results
      showed the chimpanzee was unable to detect the probe in the lower left quadrant
      of the visual field, suggesting severe loss of contrast sensitivity in a part of
      hemivisual field that is retinotopically corresponded to the hemisphere of the
      cyst. A chimpanzee with a naturally occurring deficit in the right striate cortex
      and the availability of remote eye-tracking technology presented a unique
      opportunity to compare the role of the occipital lobe in visually guided behavior
      among various primate species.

PMID- 24036353
TI  - Histology-derived volumetric annotation of the human hippocampal subfields in
      postmortem MRI.
AB  - Recently, there has been a growing effort to analyze the morphometry of
      hippocampal subfields using both in vivo and postmortem magnetic resonance
      imaging (MRI). However, given that boundaries between subregions of the
      hippocampal formation (HF) are conventionally defined on the basis of microscopic
      features that often lack discernible signature in MRI, subfield delineation in
      MRI literature has largely relied on heuristic geometric rules, the validity of
      which with respect to the underlying anatomy is largely unknown. The development
      and evaluation of such rules are challenged by the limited availability of data
      linking MRI appearance to microscopic hippocampal anatomy, particularly in three
      dimensions (3D). The present paper, for the first time, demonstrates the
      feasibility of labeling hippocampal subfields in a high resolution volumetric MRI
      dataset based directly on microscopic features extracted from histology. It uses
      a combination of computational techniques and manual post-processing to map
      subfield boundaries from a stack of histology images (obtained with 200MUm
      spacing and 5MUm slice thickness; stained using the Kluver-Barrera method) onto a
      postmortem 9.4Tesla MRI scan of the intact, whole hippocampal formation acquired
      with 160MUm isotropic resolution. The histology reconstruction procedure consists
      of sequential application of a graph-theoretic slice stacking algorithm that
      mitigates the effects of distorted slices, followed by iterative affine and
      diffeomorphic co-registration to postmortem MRI scans of approximately 1cm-thick
      tissue sub-blocks acquired with 200MUm isotropic resolution. These 1cm blocks are
      subsequently co-registered to the MRI of the whole HF. Reconstruction accuracy is
      evaluated as the average displacement error between boundaries manually
      delineated in both the histology and MRI following the sequential stages of
      reconstruction. The methods presented and evaluated in this single-subject study
      can potentially be applied to multiple hippocampal tissue samples in order to
      construct a histologically informed MRI atlas of the hippocampal formation. 

PMID- 24036356
TI  - Processing consequences of superfluous and missing prosodic breaks in auditory
      sentence comprehension.
AB  - This ERP study investigates whether a superfluous prosodic break (i.e., a
      prosodic break that does not coincide with a syntactic break) has more severe
      processing consequences during auditory sentence comprehension than a missing
      prosodic break (i.e., the absence of a prosodic break at the position of a
      syntactic break). Participants listened to temporarily ambiguous sentences
      involving a prosody-syntax match or mismatch. The disambiguation of these
      sentences was always lexical in nature in the present experiment. This contrasts
      with a related study by Pauker, Itzhak, Baum, and Steinhauer (2011), where the
      disambiguation was of a lexical type for missing PBs and of a prosodic type for
      superfluous PBs. Our results converge with those of Pauker et al. (2011):
      superfluous prosodic breaks lead to more severe processing problems than missing
      prosodic breaks. Importantly, the present results extend those of Pauker et al.
      (2011) showing that this holds when the disambiguation is always lexical in
      nature. Furthermore, our results show that the way listeners use prosody can
      change over the course of the experiment which bears consequences for future
      studies. 

PMID- 24036357
TI  - Action, agency and responsibility.
AB  - In a series of experiments Marc Jeannerod revealed that we have very little
      awareness of the details and causes of our actions. We are, however, vividly
      aware of being in control of our actions and this gives us a sense of
      responsibility. These feelings arise, first, from intentional binding which
      creates a perception of agency, linking an intentional action to its outcome and,
      second, from the counterfactual reasoning that we could have chosen some other
      action. These feelings of responsibility play a critical role in creating social
      cohesion since they allow people to be held to account for deliberate antisocial
      behaviour. Jeannerod's studies also showed that we are unaware of how little we
      know about our actions and so are happy to make up stories about the nature and
      causes of our behaviour. These stories often do not correspond with the
      underlying cognitive and neural processes, but they can be changed through
      instructions and through discussion with others. Our experience of responsibility
      for action emerges during our upbringing through exposure to our culture. This
      creates consensus about the causes of behaviour, but not necessarily accuracy. 

PMID- 24036359
TI  - Electrophysiological correlates of the retention of tones differing in timbre in
      auditory short-term memory.
AB  - We examined the electrophysiological correlates of retention in auditory short
      term memory (ASTM) for sequences of one, two, or three tones differing in timbre
      but having the same pitch. We focused on event-related potentials (ERPs) during
      the retention interval and revealed a sustained fronto-central ERP component
      (most likely a sustained anterior negativity; SAN) that became more negative as
      memory load increased. Our results are consistent with recent ERP studies on the
      retention of pitch and suggest that the SAN reflects brain activity mediating the
      low-level retention of basic acoustic features in ASTM. The present work shows
      that the retention of timbre shares common features with the retention of pitch,
      hence supporting the notion that the retention of basic sensory features is an
      active process that recruits modality-specific brain areas. 

PMID- 24036358
TI  - Action-perception coupling in kinesthesia: a new approach.
AB  - According to recent findings, intentional motor actions are controlled by
      resetting the referent position, R, at which neuromuscular elements, including
      reflexes, begin to act. It is suggested that somatosensory afferents inform the
      brain about the deviation (P) of body segments from the centrally set referent
      position. To perceive the actual position (Q) of body segments and form the
      position sense (PS), the central and afferent signals are combined: Q=R+P. In
      previous studies, the R has been shown to remain invariant during involuntary
      changes in the wrist position elicited by sudden unloading of muscles, suggesting
      that only the afferent component is responsible for the PS during this reflex. In
      contrast, the central PS component, R, is predominantly responsible for PS during
      intentional motion in isotonic conditions. We tested the hypothesis that the R
      and P are interchangeable PS components such that involuntary changes in wrist
      position elicited by the unloading reflex can easily be reproduced by making
      intentional changes in wrist position in isotonic conditions, in the absence of
      vision. The PS rule also suggests that PS is independent of sense of effort,
      which was tested by asking subjects to reproduce elbow joint angles under
      different constant loads. We also tested the hypothesis that tendon vibration may
      elicit motion that may not be perceived by subjects (no-motion illusion). These
      hypotheses were confirmed in three experiments. It is concluded that the R and P
      are additive components of PS and that, contrary to the conventional view, PS is
      independent of the sense of effort or efference copy. The PS rule also explains
      kinesthetic illusions and the phantom limb phenomenon. This study advances the
      understanding of action-perception coupling in kinesthesia. 

PMID- 24036360
TI  - The influence of worry and avoidance on the Iowa Gambling Task.
AB  - BACKGROUND: It has been proposed that worry in individuals with Generalized
      Anxiety Disorder may be reinforced by a positive effect of worry on decision
      making, as reflected by a steeper learning curve on the Iowa Gambling Task (IGT).
      We hypothesized that this apparent positive effect of worry is dependent on the
      IGT parameters, in particular the absence of an opportunity to avoid decisions.
      OBJECTIVE: (1) To replicate previous findings on the effect of worry on IGT
      performance. (2) To examine the influence of avoidance opportunity on IGT
      performance. We hypothesized that the positive effect of worry on learning would
      be abolished or reversed by the opportunity to avoid. METHOD: A standard IGT and
      a new IGT version that includes a pass (avoidance) option were completed by 78
      and 79 participants, respectively. RESULTS: A beneficial effect of worry on
      learning in the standard version of the IGT was not observed. In the pass version
      of the IGT, worry status and avoidance were negatively associated with
      performance. Worry was not related, however, to pass usage. The hypothesized
      mediating effect of avoidance was non-significant. LIMITATIONS: It is unclear to
      what extent these findings generalize to real-life decision making and how
      clinical status affects results. CONCLUSION: The possibility to avoid a decision
      results in poorer IGT performance in high relative to low trait worriers.
      Possible explanations for these findings are discussed.

PMID- 24036361
TI  - The translation initiation factor 3 subunit eIF3K interacts with PML and
      associates with PML nuclear bodies.
AB  - The promyelocytic leukemia protein (PML) is a tumor suppressor protein that
      regulates a variety of important cellular processes, including gene expression,
      DNA repair and cell fate decisions. Integral to its function is the ability of
      PML to form nuclear bodies (NBs) that serve as hubs for the interaction and
      modification of over 90 cellular proteins. There are seven canonical isoforms of
      PML, which encode diverse C-termini generated by alternative pre-mRNA splicing.
      Recruitment of specific cellular proteins to PML NBs is mediated by protein
      protein interactions with individual PML isoforms. Using a yeast two-hybrid
      screen employing peptide sequences unique to PML isoform I (PML-I), we identified
      an interaction with the eukaryotic initiation factor 3 subunit K (eIF3K), and in
      the process identified a novel eIF3K isoform, which we term eIF3K-2. We further
      demonstrate that eIF3K and PML interact both in vitro via pull-down assays, as
      well as in vivo within human cells by co-immunoprecipitation and co
      immunofluorescence. In addition, eIF3K isoform 2 (eIF3K-2) colocalizes to PML
      bodies, particularly those enriched in PML-I, while eIF3K isoform 1 associates
      poorly with PML NBs. Thus, we report eIF3K as the first known subunit of the eIF3
      translation pre-initiation complex to interact directly with the PML protein, and
      provide data implicating alternative splicing of both PML and eIF3K as a possible
      regulatory mechanism for eIF3K localization at PML NBs.

PMID- 24036362
TI  - Evaluation of two modified quick, easy, cheap, effective, rugged and safe
      (QuEChERS) sample preparation methods for the analysis of baclofen and gabapentin
      in feeds by liquid chromatography tandem mass spectrometry.
AB  - This paper presents a new analytical method for the simultaneous determination of
      baclofen and gabapentin in feeds based on two modified quick, easy, cheap,
      effective, rugged and safe (QuEChERS) sample preparation methods and liquid
      chromatography tandem mass spectrometry (LC-MS/MS). For the two modified QuEChERS
      methods, samples were first extracted with acidified acetonitrile (5.0% acetic
      acid, v/v) without using acetonitrile salting-out extraction. Then, the first
      modified QuEChERS method was established according to the original QuEChERS
      cleanup procedure. For the second modified QuEChERS method, the extract was
      evaporated to dryness and reconstituted in acetonitrile. Subsequently, the
      analytes in the reconstituted solution were retained by primary secondary amine
      (PSA) and released from PSA with 1.0% formic acid in methanol. Finally, the
      eluate was evaporated and dissolved in 0.1% formic acid solution/methanol (v/v,
      80:20). All of the samples were analyzed by LC-MS/MS on a Waters Acquity BEH C18
      column with 0.1% formic acid in water/methanol as the mobile phase with gradient
      elution. The matrix effect, recovery, and repeatability, within laboratory
      reproducibility, and the LODs and LOQs of the two modified QuEChERS sample
      preparation methods were investigated and compared. Comparative results showed
      that the second method was obviously superior to the first method. 

PMID- 24036363
TI  - High-throughput determination of nonsteroidal anti-inflammatory drugs in human
      plasma by HILIC-MS/MS.
AB  - A simple and sensitive method was developed and validated here for the analysis
      of thirteen nonsteroidal anti-inflammatory drugs (NSAIDs) in human plasma samples
      by hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry
      (MS/MS). A small volume of plasma (20MUL) spiked with compounds was diluted with
      80MUL of 10-mM ammonium acetate followed by a simple protein precipitation with
      400MUL of acetonitrile. After centrifugation, the clear supernatant extract was
      directly injected into the HILIC-MS/MS, without any solvent evaporation and
      reconstitution steps. The chromatographic separation of the NSAIDs was achieved
      on a Unison UK-Amino HILIC column (50mm*3mm i.d., particle size 3MUm) with a
      linear gradient elution system composed of 10mM ammonium acetate (pH 6.8) and
      acetonitrile at a flow rate of 0.4mL/min. The mass spectra obtained by HILIC-MS
      showed base peak ions due to [M+H](+) for indomethacin, oxaprozin, ketoprofen,
      alminoprofen, zaltoprofen, tiaprofenic acid, pranoprofen, and ketoprofen-d3 and
      due to [M-H](-) for etodolac, ibuprofen, diclofenac, fenoprofen, loxoprofen,
      naproxen, and ibuprofen-d3. Recoveries of these thirteen NSAIDs in plasma were
      34.8-113% and the lower limits of quantitation were 0.125-1.25MUg/mL. The intra-
      and interday coefficient of variations for all drugs in plasma were less than
      14.6%. The data obtained from actual plasma determinations of zaltoprofen,
      ibuprofen, and diclofenac are also presented. 

PMID- 24036364
TI  - Parallel achiral-chiral determination of oxybutynin, N-desethyl oxybutynin and
      their enantiomers in human plasma by LC-MS/MS to support a bioequivalence trial.
AB  - A parallel achiral and chiral determination of oxybutynin, its pharmacologically
      active metabolite N-desethyl oxybutynin and their enantiomers in human plasma is
      described using LC-MS/MS. Both the methods were developed and validated using
      deuterated analogues as internal standards. Achiral analysis of racemic
      oxybutynin and N-desethyl oxybutynin was carried out on Phenomenex Gemini C18
      (150mm*4.6mm, 5MUm) column under isocratic conditions using acetonitrile-5.0mM
      ammonium acetate, pH 4.0 (90:10, v/v) as the mobile phase. Separation of (S)- and
      (R)-enantiomers of the analytes was performed on Phenomenex Lux Amylose-2
      (150mm*4.6mm, 3MUm) chiral column using a mixture of solvent A [acetonitrile:10mM
      ammonium bicarbonate, 80:20 (v/v)] and solvent B [2-propanol:methanol, 50:50
      (v/v)] in 20:80 (v/v) ratio as the mobile phase. Plasma samples were prepared by
      liquid-liquid extraction with ethyl acetate-diethyl ether-n-hexane solvent
      mixture. A linear range was established from 0.025 to 10.0ng/mL and 0.25 to
      100ng/mL for the enantiomers of oxybutynin and N-desethyl oxybutynin
      respectively. The extraction recovery varied from 96.0 to 105.1%, while the IS
      normalized matrix factors ranged from 0.96 to 1.07 for all the enantiomers. The
      validated method was applied for a pilot bioequivalence study with 5mg oxybutynin
      tablet formulation in 8 healthy subjects. The pharmacokinetic profiles showed
      that the plasma concentration of (R)-oxybutynin was lower than that of (S)
      oxybutynin, while a reverse trend was observed for the enantiomers of N-desethyl
      oxybutynin. The reproducibility in the measurement of study data was demonstrated
      by reanalysis of 20 incurred samples. 

PMID- 24036365
TI  - Physiological role of hydrogen sulfide and polysulfide in the central nervous
      system.
AB  - Hydrogen sulfide (H2S) is a well-known toxic gas that has the smell of rotten
      eggs. This pungent gas was considered as a physiological mediator, after the
      identification of endogenous sulfides in the mammalian brain. H2S is produced
      from L-cysteine by enzymes such as cystathionine beta-synthase (CBS),
      cystathionine gamma-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST)
      along with cysteine aminotransferase (CAT). We recently identified a fourth
      pathway, where H2S is produced from D-cysteine by the enzyme D-amino acid oxidase
      (DAO) along with 3MST. We demonstrated that H2S is a neuromodulator that
      facilitates hippocampal long-term potentiation (LTP) by enhancing the activity of
      N-methyl-D-aspartate (NMDA) receptors. It also induces Ca(2+) influx in the
      astrocytes by activating the transient receptor potential ankyrin-1 (TRPA1)
      channels. In addition to being a signaling molecule, it also functions as a
      neuroprotective agent by enhancing the production of glutathione, a major
      intracellular antioxidant that scavenges the reactive oxygen species (ROS) in the
      mitochondria. H2S regulates the activity of the enzymes by incorporating the
      bound sulfane sulfur to cysteine residues. This modification is known as
      sulfhydration or sulfuration. The neuroprotective ubiquitin E3 ligase, parkin,
      enhances its neuroprotective activity by this modification. This review is
      focused on the functional role of H2S as a signaling molecule and as a
      cytoprotectant in the nervous system. In addition, this review shows the recent
      findings that indicate that the H2S-derived polysulfides found in the brain
      activate TRPA1 channels more potently than parental H2S.

PMID- 24036366
TI  - Cellular FLICE-like inhibitory protein secures intestinal epithelial cell
      survival and immune homeostasis by regulating caspase-8.
AB  - BACKGROUND & AIMS: The intestinal epithelium generates a barrier that protects
      mammals from potentially harmful intestinal contents, such as pathogenic
      bacteria. Dysregulation of epithelial cell death has been implicated in barrier
      dysfunction and in the pathogenesis of intestinal inflammation. We investigated
      mechanisms of cell-death regulation in the intestinal epithelium of mice.
      METHODS: Conditional knockout mice (either inducible or permanent) with deletion
      of cellular FLICE-inhibitory protein (cFlip) or caspase-8 in the intestinal
      epithelium were analyzed by histology and high-resolution endoscopy. We assessed
      the effects of cFlip or caspase-8 deficiency on intestinal homeostasis. RESULTS:
      Expression of cFlip in the intestinal epithelium was required for constitutive
      activation of caspase-8 under steady-state conditions. Intestinal expression of
      cFlip was required for development; disruption of the gene encoding cFlip from
      the intestinal epithelium (cFlip(fl/fl) VillinCre(+) mice) resulted in embryonic
      lethality. When cFlip was deleted from the intestinal epithelium of adult mice
      (cFlip(iDeltaIEC) mice), the animals died within a few days from severe tissue
      destruction, epithelial cell death, and intestinal inflammation. Death of cFlip
      depleted intestinal epithelial cells was regulated extrinsically and required the
      presence of death receptor ligands, such as tumor necrosis factor-alpha and CD95
      ligand, but was independent of receptor-interacting protein 3. cFlip deficiency
      was associated with strong up-regulation of caspase-8 and caspase-3 activity and
      excessive apoptosis in intestinal crypts. CONCLUSIONS: cFlip is required for
      intestinal tissue homeostasis in mice. It controls the level of activation of
      caspase-8 to promote survival of intestinal epithelial cells.

PMID- 24036367
TI  - Perilipins: lipid droplet coat proteins adapted for tissue-specific energy
      storage and utilization, and lipid cytoprotection.
AB  - Cytosolic lipid storage droplets are primary functional organelles that regulate
      cellular lipid metabolism and homeostasis. Paradoxically, excess lipid stores are
      linked to both adaptive (fasting and chronic exercise) and mal-adaptive (obesity
      and related health complications) conditions. Thus, collective metabolic and
      physiological processes must balance lipid storage and utilization with
      prevention of lipocytotoxicity and compounding tissue dysfunctions, urging the
      need to further define the connection of mammalian lipid droplet function and
      lipid homeostasis. The perilipins are a multi-protein family that targets lipid
      droplet surfaces and regulates lipid storage and hydrolysis. Study of perilipin
      functions has provided insight into the physiological roles of cytosolic lipid
      droplets and their relationship with obesity-related pathologies. Here, we review
      the current knowledge of the multiple perilipin proteins in regulating tissue
      specific lipid droplets and associations with tissue and systemic energetics. 

PMID- 24036368
TI  - Wnt signaling in liver fibrosis: progress, challenges and potential directions.
AB  - Liver fibrosis is a common wound-healing response to chronic liver injuries,
      including alcoholic or drug toxicity, persistent viral infection, and genetic
      factors. Myofibroblastic transdifferentiation (MTD) is the pivotal event during
      liver fibrogenesis, and research in the past few years has identified key
      mediators and molecular mechanisms responsible for MTD of hepatic stellate cells
      (HSCs). HSCs are undifferentiated cells which play an important role in liver
      regeneration. Recent evidence demonstrates that HSCs derive from mesoderm and at
      least in part via septum transversum and mesothelium, and HSCs express markers
      for different cell types which derive from multipotent mesenchymal progenitors.
      There is a regulatory commonality between differentiation of adipocytes and that
      of HSC, and the shift from adipogenic to myogenic or neuronal phenotype
      characterizes HSC MTD. Central of this shift is a loss of expression of the
      master adipogenic regulator peroxisome proliferator activated receptor gamma
      (PPARgamma). Restored expression of PPARgamma and/or other adipogenic
      transcription genes can reverse myofibroblastic HSCs to differentiated cells.
      Vertebrate Wnt and Drosophila wingless are homologous genes, and their translated
      proteins have been shown to participate in the regulation of cell proliferation,
      cell polarity, cell differentiation, and other biological roles. More recently,
      Wnt signaling is implicated in human fibrosing diseases, such as pulmonary
      fibrosis, renal fibrosis, and liver fibrosis. Blocking the canonical Wnt signal
      pathway with the co-receptor antagonist Dickkopf-1 (DKK1) abrogates these
      epigenetic repressions and restores the gene PPARgamma expression and HSC
      differentiation. The identified morphogen mediated epigenetic regulation of
      PPARgamma and HSC differentiation also serves as novel therapeutic targets for
      liver fibrosis and liver regeneration. In conclusion, the Wnt signaling promotes
      liver fibrosis by enhancing HSC activation and survival, and we herein discuss
      what we currently know and what we expect will come in this field in the next
      future. 

PMID- 24036369
TI  - Silibinin ameliorates steatosis and insulin resistance during non-alcoholic fatty
      liver disease development partly through targeting IRS-1/PI3K/Akt pathway.
AB  - Silibinin (SIL) is a well-studied hepato-protective agent against a spectrum of
      liver diseases. However, the role of SIL in non-alcoholic fatty liver disease
      (NAFLD) induced insulin resistance and underlying signaling is not fully
      characterized. In this study, Sprague-Dawley (SD) rats were fed with high-fat
      diet to develop NAFLD with or without an SIL co-treatment. NAFLD rats showed
      typical NAFLD symptoms including histological changes, insulin resistance, and
      glucose metabolism dysfunction. SIL co-treatment significantly ameliorated these
      pathological features partly through restoring the IRS-1/PI3K/Akt pathway. In
      addition, BRL-3A and HepG2 cells were incubated with palmitic acid (PA) to induce
      steatosis. SIL co-treatment in cells also reduced lipid accumulation, recovered
      cell viability, and down-regulated the protein expression of resistin, the marker
      for insulin resistance. Specific blocker of PI3K abolished the ameliorative
      effects of SIL on cellular steatosis. In conclusion, SIL alleviated steatosis and
      insulin resistance both in vivo and in vitro partly through regulating the IRS
      1/PI3K/Akt pathway. 

PMID- 24036370
TI  - 1,25-Dihydroxyvitamin D3-3-bromoacetate, a novel vitamin D analog induces
      immunosuppression through PI3K/Akt/mTOR signaling cascade.
AB  - PURPOSE: The molecular mechanism responsible for the immunomodulatory effect of
      1,25-dihydroxyvitamin D3 (Vit-D) is still not well elucidated. Unavoidable
      systemic toxicity of Vit-D has encouraged to develop more potent and less toxic
      Vit-D analogs, such as 1,25-dihydroxyvitamin D3-3-bromoacetate (BE). Our aim was
      to explore the immunosuppressive effect of BE and its molecular mechanism in
      autoimmune diseases. METHOD: Magnetically sorted CD3(+) T cells (T cells) from
      PBMCs of psoriasis and autoimmune arthritis patients were cultured with/without
      BE and Vit-D followed by proliferation (MTT, CFSE dilution assays) and apoptosis
      assays (annexin V). Immunoblot was performed to determine the signaling cascade
      responsible for the antiproliferative effect. RESULTS: In MTT assay, BE (OD:
      0.64+/-0.08) markedly inhibited the anti-CD3/CD28 stimulated proliferation of T
      cells (OD: 1.8+/-0.30, p<0.001) and at equivalent doses, the inhibitory effect
      was more than that of Vit-D (OD: 0.91+/-0.11, p<0.05). The antiproliferative
      effect of BE was extended to activated CD4(+) and CD8(+) memory T cells (CD45RA(
      )CD11a(+)) without much effect on the naive T cells. BE induced more apoptosis of
      T cells (45.01+/-4.27%, p<0.01) compared to untreated cells (3.45+/-1.8%), and
      the proapoptotic effect was markedly more than that of Vit-D (26.1+/-2.05%,
      p<0.05). BE effectively inhibited the anti-CD3/CD28-induced phosphorylation of
      Akt and mTOR and in both, BE showed more potency than Vit-D (p<0.05). CONCLUSION:
      Topical Vit-D is being used successfully in psoriasis for years. However, its
      potency is less compared to topical corticosteroids. The de novo BE showed
      significantly more immunosuppression than conventional Vit-D and the
      immunosuppressive effect is PI3K/Akt/mTOR dependent. Our results indicate that BE
      could be an effective therapeutic agent for psoriasis and other T-cell-mediated
      autoimmune diseases.

PMID- 24036371
TI  - High-level expression of a full-length Eph receptor.
AB  - Eph receptors are the largest family of Receptor Tyrosine Kinases containing a
      single membrane-spanning segment. They are involved in a various developmental
      and cell-cell communication events. Although there is extensive structural
      information available on both the extra- and intracellular regions of Eph's in
      isolation, no structures are available for the entire receptor. To facilitate
      structural studies on functionally relevant Eph/ephrin complexes, we have
      developed an expression system for producing the full-length human EphA2
      receptor. We successfully expressed milligram amounts of the receptor using
      baculovirus-based vector and insect cells. We were also able to extract the
      protein from the cell membranes and purify it to near homogeneity in two simple
      steps. The purified receptor was shown to retain its biological activity in terms
      of both binding to its functional ligands and being able to auto-phosphorylate
      the key tyrosine residues of the cytoplasmic kinase domain. 

PMID- 24036372
TI  - Dissecting the doctor-dancer relationship: health care decision making among
      American collegiate dancers.
AB  - OBJECTIVE: To examine perceptual influences on dancers' health care-seeking
      decisions and whether dancers' beliefs correlate with actual use of provider
      services when they are injured. Secondary aims were to understand how dancers may
      select physicians and what they consider to be the most important features of the
      medical consultation. DESIGN: Prospective cohort study. SETTING: University and
      conservatory dance departments. PARTICIPANTS: Forty American collegiate dancers.
      ASSESSMENT OF RISK FACTORS: Before the start of the dance semester, all
      participants completed a retrospective survey that included baseline demographic
      data, dance experience, a dance-related injury (DRI) inventory, previous health
      care exposures, and perceptions regarding health care treatment providers. Data
      regarding new DRIs and health care exposures were then prospectively collected
      every 2 weeks for 6 months. MAIN OUTCOME MEASUREMENTS: A DRI was defined as any
      neuromusculoskeletal condition sustained as the result of dancing activity that
      caused a dancer to stop or modify his or her dancing for more than 3 consecutive
      days. RESULTS: Dancers perceived dance teachers to be first-line treatment
      providers (47.5%), followed by physical therapists (PTs; 30%). Physicians were
      ranked third (12.5%) and only marginally higher than a dance colleague (10%). The
      dancers expressed a strong preference for nonsurgical rather than surgical
      physicians (87.5% versus 5.0%), and among physicians, the majority of dancers
      preferred subspecialists (60%), namely nonsurgical sports medicine doctors and
      physiatrists. During the 6-month prospective data-collection period, 25 dancers
      (69.4%) sustained 55 unique injuries, with 22 dancers (88%) and 34 injuries
      (61.8%) undergoing evaluation. Only 17.7% of injuries were evaluated by a
      physician. Dancers showed greater incongruity between their preinjury perceptions
      and postinjury use of physicians than they did with PTs (P = .0002). CONCLUSIONS:
      Although dancers did not perceive physicians to be first-line treatment providers
      for DRIs, these perceptions about physicians were poorly correlated with use.
      Instead, injured dancers' health care-seeking behaviors were more likely related
      to relatively decreased barriers to other nonphysician providers, as well as pre
      existing referral pathways to PTs.

PMID- 24036373
TI  - Therapeutic potential of a novel cannabinoid agent CB52 in the mouse model of
      experimental autoimmune encephalomyelitis.
AB  - Multiple Sclerosis (MS) is a demyelinating disease which causes inflammation,
      demyelination, and axonal injury. Currently, there is no cure for the disease.
      The endocannabinoid system has recently emerged as a promising therapeutic target
      for MS. The protective mechanisms of cannabinoids are thought to be mediated by
      the activation of the cannabinoid type 1 (CB1) and type 2 (CB2) receptors
      expressed primarily in neurons and immune cells, respectively. However, the
      molecular mechanisms and the contribution of each receptor in ameliorating
      disease progression are still debatable. Although CB1 and CB2 receptors are
      expressed in oligodendrocytes, the myelin producing cells in the central nervous
      system, the role of cannabinoids in oligodendrocyte survival has not been well
      investigated. Using primary cultures of mature oligodendrocytes, we tested the
      effect of a novel synthetic cannabinoid CB52 on oligodendrocyte toxicity induced
      by peroxynitrite, the primary toxic species released by microglia. Interestingly,
      we found that CB52 is more potent than a number of broad and selective CB1 and
      CB2 agonists in protecting oligodendrocytes against peroxynitrite-induced
      toxicity. The protection provided by CB52 is likely due to its reduction of
      ERK1/2 phosphorylation and reactive oxygen species (ROS) generation in these
      cells. Using experimental autoimmune encephalomyelitis (EAE), an animal model of
      MS, we found that CB52 reduces microglia activation, nitrotyrosine formation, T
      cell infiltration, oligodendrocyte toxicity, myelin loss and axonal damage in the
      mouse spinal cord white matter and alleviates the clinical scores when given
      either before or after disease onset. These effects are reversed by the CB1
      receptor antagonist, but not by the CB2 receptor antagonist, suggesting that the
      activation of CB1 receptors contributes significantly to the anti-inflammatory
      and neuroprotective effects of cannabinoids on MS. 

PMID- 24036374
TI  - Cortical spreading depression induces oxidative stress in the trigeminal
      nociceptive system.
AB  - Indirect evidence suggests the increased production of reactive oxygen species
      (ROS) in migraine pathophysiology. In the current study we measured lipid
      peroxidation product in the rat cortex, trigeminal ganglia and meninges after the
      induction of cortical spreading depression (CSD), a phenomenon known to be
      associated with migraine aura, and tested nociceptive firing triggered by ROS in
      trigeminal nerves ex vivo. Application of KCl to dura mater in anesthetized rats
      induced several waves of CSD recorded by an extracellular electrode in the
      cortex. Following CSD, samples of cortex (affected regions were identified with
      blood oxygen level-dependent (BOLD) functional magnetic resonance imaging
      (fMRI)), meninges from left and right hemispheres and trigeminal ganglia were
      taken for biochemical analysis. We found that CSD increased the level of the
      lipid peroxidation product malondialdehyde (MDA) in the ipsilateral cerebral
      cortex and meninges, but also in both ipsi- and contralateral trigeminal ganglia.
      In order to test the pro-nociceptive action of ROS, we applied the mild oxidant
      hydrogen peroxide to isolated rat hemiskull preparations including preserved
      trigeminal innervations. Application of hydrogen peroxide to meninges transiently
      enhanced electrical spiking activity of trigeminal nerves showing a pro
      nociceptive action of ROS. In the presence of hydrogen peroxide trigeminal nerves
      still responded to capsaicin by burst of spiking activity indicating integrity of
      neuronal structures. The action of hydrogen peroxide was mediated by TRPA1
      receptors as it was abolished by the specific TRPA1 antagonist TCS-5861528. Using
      dorsal root ganglion sensory neurons as test system we found that hydrogen
      peroxide promoted the release of the migraine mediator calcitonin gene-related
      peptide (CGRP), which we previously identified as a trigger of delayed
      sensitization of trigeminal neurons. Our data suggest that, after CSD, oxidative
      stress spreads downstream within the trigeminal nociceptive system and could be
      involved in the coupling of CSD with the activation of trigeminovascular system
      in migraine pathology. 

PMID- 24036375
TI  - Membrane microdomain determines the specificity of receptor-mediated modulation
      of Kv7/M potassium currents.
AB  - The Kv7/M current is one of the major mechanisms controlling neuronal
      excitability, which can be modulated by activation of the G protein-coupled
      receptor (GPCR) via distinct signaling pathways. Membrane microdomains known as
      lipid rafts have been implicated in the specificity of various cell signaling
      pathways. The aim of this study was to understand the role of lipid rafts in the
      specificity of Kv7/M current modulation by activation of GPCR. Methyl-beta
      cyclodextrin (MbetaCD), often used to disrupt the integrity of lipid rafts,
      significantly reduced the bradykinin receptor (B2R)-induced but not muscarinic
      receptor (M1R)-induced inhibition of the Kv7/M current. B2R and related signaling
      molecules but not M1R were found in caveolin-containing raft fractions of the rat
      superior cervical ganglia. Furthermore, activation of B2R resulted in
      translocation of additional B2R into the lipid rafts, which was not observed for
      the activation of M1R. The increase of B2R-induced intracellular Ca(2+) was also
      greatly reduced after MbetaCD treatment. Finally, B2R but not M1R was found to
      interact with the IP3 receptor. In conclusion, the present study implicates an
      important role for lipid rafts in mediating specificity for GPCR-mediated
      inhibition of the Kv7/M current. 

PMID- 24036376
TI  - Exploration of supraspinal mechanisms in effects of spinal cord stimulation: role
      of the locus coeruleus.
AB  - The neurobiological mechanisms of spinal cord stimulation (SCS) when applied for
      neuropathic pain are still incompletely known. Previous research indicates that
      brainstem circuitry is pivotal for the SCS effect. The present study aims at
      exploring the possible contribution to the SCS effects of the pain controlling
      system emanating from the locus coeruleus (LC) in the brain stem. Experiments
      were performed on the rat-spared nerve injury pain model. After evaluation of the
      attenuation of mechanical hypersensitivity induced by SCS, the effects of SCS on
      neuronal activity in the LC and on the noradrenaline (NA) content in the dorsal
      spinal cord were analyzed. SCS produced a significant increase in the discharge
      rate of LC neurons only in rats behaviorally responding to SCS as compared to non
      responding and control animals. The NA content in the dorsal quadrant of the
      spinal cord ipsilateral to the nerve injury was analyzed using enzyme-linked
      immunosorbent assay in responding, non-responding and intact control rats both
      immediately following SCS and without SCS. No differences were found between
      these groups. In awake animals, lidocaine silencing of the ipsilateral LC or
      blocking of spinal noradrenergic system by intrathecal administration of alpha1,2
      adrenoceptor antagonists failed to influence the antihypersensitivity effect of
      SCS. The present results indicate that the SCS-induced control of
      hypersensitivity in an experimental animal model of peripheral neuropathic pain
      may not be explained by the activation of direct spinal projections of
      noradrenergic LC neurons, while supraspinal projections of LC neurons still may
      play a role in the SCS effect. 

PMID- 24036377
TI  - Chloride channel 4 is required for nerve growth factor-induced TrkA signaling and
      neurite outgrowth in PC12 cells and cortical neurons.
AB  - We have previously shown that chloride ion flux plays an important role in
      receptor tyrosine kinase A (TrkA)-mediated signaling pathway during nerve growth
      factor (NGF)-induced differentiation in pheochromocytoma (PC12) cells. Here we
      found out that chloride channel 4 (CLC-4) is responsible for the NGF-induced
      neurite outgrowth in neuronal cells. Using a patch-clamp technique, we found that
      NGF treatment increased anionic conductance in PC12 cells, an effect which was
      blocked by transfection of siRNA of CLC-4. Also, the NGF-induced TrkA
      phosphorylation and subsequent Akt/moesin phosphorylation was suppressed in the
      CLC-4 knock down cells. Moreover, CLC-4 knock down also suppressed the neurite
      outgrowth in response to long-term treatment of NGF in PC12 cells and in primary
      cortical neurons. In summary, our results suggest that CLC-4 is an important
      mediator of the TrkA-mediated signaling pathway and thus, the NGF-induced
      differentiation of neuronal cells. 

PMID- 24036378
TI  - Comparison of CHADS2 and CHA2DS2-VASC anticoagulation recommendations: evaluation
      in a cohort of atrial fibrillation ablation patients.
AB  - AIMS: Atrial fibrillation (AF) is associated with a high incidence of
      strokes/thromboembolism. The CHADS2 score assigns points for several clinical
      variables to identify stroke risk. The CHA2DS2-VASC score uses the same variables
      but also incorporates age 65 to 74, female gender, and vascular disease in an
      effort to provide a more refined risk of stroke/thromboembolism. We aimed to
      examine oral anticoagulation (OAC) recommendations for a cohort of patients
      undergoing AF ablation depending upon whether thrombo-embolic risk was determined
      by the CHADS2 or CHA2DS2-VASC score. METHODS AND RESULTS: For 1411 patients we
      compared OAC recommendations for each of these risk stratification schemes to one
      of the three OAC strategies: (i) NO-OAC, (ii) CONSIDER-OAC, and (iii) DEFINITE
      OAC. Compared with the CHADS2 score, the CHA2DS2-VASC score reduced NO-OAC from
      40.3 to 21.8% and CONSIDER-OAC from 36.6 to 27.9% while increasing DEFINITE-OAC
      from 23.0 to 50.2% of patients. Age 65 to 74 and female gender accounted for
      95.2% and vascular disease for only 4.8% of recommendations for more aggressive
      OAC using CHA2DS2-VASC. Most vascular disease occurred in patients with higher
      CHADS2 scores already recommended for DEFINITE-OAC (P < 0.0001). Reclassifying 30
      females of age <65 with a CHA2DS2-VASC score of 1 to the NO-OAC group had minimal
      effect on the overall recommendations. CONCLUSION: Compared with the CHADS2
      score, in our AF ablation population, the CHA2DS2-VASC score markedly increases
      the number of AF patients for whom OAC is recommended. It will be important to
      determine by randomized trials if this major paradigm shift to greater use of OAC
      using the CHA2DS2-VASC scoring improves patient outcomes.

PMID- 24036380
TI  - Deoxygenation at the C3 position of D- and L-arabinofuranose: stereospecific
      access to enantiomeric cordycepose derivatives.
AB  - Efficient synthesis of 3-deoxy-1,2-O-isopropylidene-beta-D- and beta-L-threo
      pentofuranose (1,2-O-isopropylidene-beta-D- and beta-L-cordycepose) was
      accomplished starting from D- and L-arabinofuranose derivatives, respectively, by
      the action of LiBH(Et)3 on corresponding intermediate 3-O-lyxofuranosyl
      trifluoromethanesulfonates.

PMID- 24036379
TI  - Loss of extracellular matrix from articular cartilage is mediated by the synovium
      and ligament after anterior cruciate ligament injury.
AB  - OBJECTIVE: Post-traumatic osteoarthritis (PTOA) occurs after anterior cruciate
      ligament (ACL) injury. PTOA may be initiated by early expression of proteolytic
      enzymes capable of causing degradation of the articular cartilage at time of
      injury. This study investigated the production of three of these key proteases in
      multiple joint tissues after ACL injury and subsequent markers of cartilage
      turnover. METHODS: ACL transection was performed in adolescent minipigs.
      Collagenase (MMP-1 and MMP-13) and aggrecanase (ADAMTS-4) gene expression changes
      were quantified in the articular cartilage, synovium, injured ligament, and the
      provisional scaffold at days 1, 5, 9, and 14 post-injury. Markers of collagen
      degradation (C2C), synthesis (CPII) and aggrecan synthesis (CS 846) were
      quantified in the serum and synovial fluid. Histologic assessment of the
      cartilage integrity (OARSI scoring) was also performed. RESULTS: MMP-1 gene
      expression was upregulated in the articular cartilage, synovium and ligament
      after ACL injury. MMP-13 expression was suppressed in the articular cartilage,
      but upregulated 100-fold in the synovium and ligament. ADAMTS-4 was upregulated
      in the synovium and ligament but not in the articular cartilage. The
      concentration of collagen degradation fragments (C2C) in the synovial joint fluid
      nearly doubled in the first five days after injury. CONCLUSION: We conclude that
      upregulation of genes coding for proteins capable of degrading cartilage ECM is
      seen within the first few days after ACL injury, and this response is seen not
      only in chondrocytes, but also in cells in the synovium, ligament and provisional
      scaffold.

PMID- 24036381
TI  - A novel polyrotaxane-based delivery system for scutellarin: preparation,
      characterization, and in vitro evaluation.
AB  - The safe and effective polyrotaxane-based drug delivery system could potentially
      increase the antiproliferative activity of antitumor medicine. A novel
      scutellarin-polyrotaxane (SCU-PR), in which scutellarin (SCU) was covalently
      bound to one of the hydroxyl groups of polyrotaxane (PR), was synthesized, and
      its characterization was further investigated by NMR, XRD, TG, DSC. The
      cytotoxicity of SCU-PR was assessed in vitro using human HCT116 and LOVO cell
      lines in results that the IC50 values of SCU-PR (1.03*10(-6) and 1.01*10(
      6)mol/L, respectively), which compared with those of free SCU (7.80*10(-5) and
      7.70*10(-5)mol/L, respectively), were lower. The valuable properties of SCU-PR
      will be potentially useful for its application on human colon cancer
      chemotherapies. 

PMID- 24036382
TI  - Impaired glucose regulation is associated with poorer performance on the Stroop
      Task.
AB  - BACKGROUND: Type 2 diabetes is a risk factor for development of cognitive
      dysfunction. Impairments in glucose regulation have been associated with poorer
      performance on tests of executive function and information processing speed.
      METHODS: We administered the Stroop Color Word Task, where higher interference
      scores are indicative of decreased selective attention, to 98 non-diabetic
      volunteers (64 m; %fat=37 +/- 12; age=36 +/- 9 yrs, race=41 NA/30 C/13 H/14 AA)
      on our inpatient unit. After 3d on a weight maintaining diet, % body fat was
      measured by DXA and a 75 g oral glucose tolerance test (OGTT) was administered.
      Impaired glucose regulation (IGR) was defined as: fasting plasma glucose >= 100
      and <= 125 mg/dL and/or 2h plasma glucose between >= 140 and <= 199 mg/dL (IGR;
      n=48; NGR; n=50). Total and incremental area under the curve (AUC) for insulin
      and glucose were calculated. RESULTS: Stroop interference scores were not
      significantly associated with any measure of adiposity or insulin concentrations.
      Individuals with IGR had significantly higher interference scores than those with
      normal glucose regulation (NGR; p=0.003). Higher interference scores were
      significantly correlated with fasting plasma glucose concentrations (r=0.26,
      p=0.007) and total glucose AUC (r=0.30, p=0.02) and only trending so for iAUC and
      2h plasma glucose (r=0.18, p=0.08; r=0.17, p=0.09 respectively). In separate
      multivariate linear models, fasting plasma glucose (p=0.002) and total glucose
      AUC (p=0.0005) remained significant predictors of Stroop interference scores,
      even after adjustment for age, sex, race, education and %fat. CONCLUSIONS:
      Individuals with IGR had decreased performance on a test of selective attention.
      Fasting plasma glucose was more strongly associated with lower performance scores
      than 2h plasma glucose. Our results indicate that even mild hyperglycemia in the
      non-diabetic range is associated with attentional processing difficulties in a
      sample of younger adults. Whether these impairments precede or are induced by
      impaired glucose regulation is not clear.

PMID- 24036383
TI  - Rhodamine-loaded intercellular adhesion molecule-1-targeted microbubbles for dual
      modality imaging under controlled shear stresses.
AB  - BACKGROUND: The ability to image incipient atherosclerosis is based on the early
      events taking place at the endothelial level. We hypothesized that the expression
      of intercellular adhesion molecule-1 even in vessels with high flow rates can be
      imaged at the molecular level using 2 complementary imaging techniques: 2-photon
      laser scanning microscopy and contrast-enhanced ultrasound. METHODS AND RESULTS:
      Using 2-photon laser scanning microscopy and contrast-enhanced ultrasound,
      intercellular adhesion molecule-1-targeted and rhodamine-loaded microbubbles were
      shown to be specifically bound to tumor necrosis factor-alpha-stimulated human
      umbilical vein endothelial cells and murine carotid arteries (44 wild-type mice)
      at shear stresses ranging from 1.25 to 120 dyn/cm(2). Intercellular adhesion
      molecule-1-targeted and rhodamine-loaded microbubbles bound 8* more efficient
      (P=0.016) to stimulated human umbilical vein endothelial cells than to
      unstimulated cells and 14* more than nontargeted microbubbles (P=0.016). In
      excised carotids, binding efficiency did not decrease significantly when
      increasing the flow rate from 0.25 to 0.6 mL/min. Higher flow rates (0.8 and 1
      mL/min) showed significantly reduced microbubbles retention, by 38% (P=0.03) and
      55% (P=0.03), respectively. Ex vivo results were translatable in vivo, confirming
      that intercellular adhesion molecule-1-targeted and rhodamine-loaded microbubbles
      are able to bind specifically to the inflamed carotid artery endothelia under
      physiological flow conditions and to be noninvasively detected using contrast
      enhanced ultrasound. CONCLUSIONS: Our data provide groundwork for the
      implementation of molecular ultrasound imaging in vessels with high shear stress
      and flow rates, as well as for the future development of image-guided therapeutic
      interventions, and multiphoton microscopy as the appropriate method of
      validation.

PMID- 24036384
TI  - Effects of age and aerobic fitness on myocardial lipid content.
AB  - BACKGROUND: Aging and sedentary lifestyles lead to cardiac atrophy, ventricular
      stiffening, and impaired diastolic function. Both conditions are marked by
      increased adiposity, which can lead to ectopic fat deposition in nonadipocyte
      tissues including the myocardium. The effect of excess intramyocardial fat on
      cardiac function in nonobese individuals is unknown. METHODS AND RESULTS: Cardiac
      lipid content was measured by magnetic resonance spectroscopy in 153 healthy
      nonobese subjects with varying fitness levels quantified by peak oxygen uptake
      during treadmill exercise. Cardiac function (echo) and left ventricular (LV)
      filling pressures (right heart catheterization) were measured under varying
      preloads. LV stiffness was calculated from a curve fit of the diastolic portion
      of the pressure-volume curve. The strongest clinical predictors of lipid content
      were body mass index (beta=+0.03; 95% confidence interval, 0.001-0.06) and peak
      oxygen uptake (beta=-0.02; 95% confidence interval, -0.03 to -0.009; R(2)=0.14;
      P<0.001). Subjects in the highest quintile had smaller LV end-diastolic volumes
      (68+/-13 versus 58+/-12 mL/m(2); P<0.01) and decreased peak early mitral annular
      and increased peak late mitral inflow velocities. There were no differences in LV
      stiffness, but a leftward shift in the pressure-volume curve suggested a less
      distensible ventricle with increasing myocardial lipid levels. After adjusting
      for age, fitness, and body mass index, echocardiographic and morphometric
      differences among groups were attenuated and no longer significant. CONCLUSIONS:
      Body mass index and fitness levels are the strongest predictors of myocardial
      lipid content in nonobese humans. Cardiac lipid content is associated with
      decreased ventricular distensibility, and it may provide a causal mechanism
      linking changes in LV function related to age and fitness.

PMID- 24036386
TI  - Value of an exercise workload >=10 metabolic equivalents for predicting inducible
      myocardial ischemia.
AB  - BACKGROUND: We sought to identify extensive ischemia on exercise echocardiography
      (ExE) relative to workload in patients without known coronary artery disease and
      to investigate whether ExE is useful in predicting outcomes in those with high
      exercise capacity (>=10 metabolic equivalents [METs]) plus a maximal test (>=85%
      of their maximal age-predicted heart rate [MAPHR]). METHODS AND RESULTS: The
      analysis was performed on 4269 patients who underwent ExE, of whom 3995 achieved
      >=85% of their MAPHR. These patients were divided according to the reached
      workload (<7, 7-9, or >=10 METs) and compared for ExE results. Outcomes in the
      group achieving >=10 METs plus >=85% of their MAPHR (n=2221) were specifically
      assessed. Ischemia was defined as new/worsening wall motion abnormalities with
      exercise. ExE results were different between groups because the METs were lower.
      Still, among patients achieving >=10 METs plus >=85% of their MAPHR, 9.3% had
      extensive ischemia and 6% multiterritory disease. During follow-up in this
      subgroup, 108 patients died and 42 had a major cardiac event. Annualized
      mortality and major cardiac event rates were 0.84% and 0.32% in patients without
      ischemia versus 2.26% and 0.84% in those with ischemia, respectively (P<0.001 and
      P=0.002, respectively). Ischemia was an independent predictor of mortality
      (hazard ratio, 1.88; 95% confidence interval, 1.23-2.89; P=0.004) and major
      cardiac event (hazard ratio, 2.39; 95% confidence interval, 1.22-4.71; P=0.01).
      CONCLUSIONS: Patients without known coronary artery disease achieving >=10 METs
      plus >=85% of their MAPHR may still have ischemia. However, the low event rates
      even in those with ischemia limit the usefulness of imaging for assessing
      outcomes in this group.

PMID- 24036385
TI  - Cardiac magnetic resonance postcontrast T1 time is associated with outcome in
      patients with heart failure and preserved ejection fraction.
AB  - BACKGROUND: The underlying pathophysiology of heart failure with preserved
      ejection fraction (HFPEF) is incompletely understood, but myocardial
      extracellular matrix accumulation is thought to play a major role. Our aims were
      to estimate myocardial extracellular matrix using cardiac magnetic resonance T1
      mapping and to assess the relationship between pathobiology/pathophysiology and
      prognosis. METHODS AND RESULTS: Patients with suspected HFPEF (n=100) were
      enrolled in this prospective, observational study. Confirmatory diagnostic tests,
      cardiac magnetic resonance imaging including T1 mapping, and invasive hemodynamic
      assessments were performed at baseline. Sixty-one patients with confirmed HFPEF
      entered a longitudinal outcome-monitoring phase (mean, 22.9+/-5.0 months), during
      which 16 had a cardiac event. Cardiac magnetic resonance T1 time (hazard ratio,
      0.99; 95% confidence interval, 0.98-0.99; P=0.046), left atrial area (hazard
      ratio, 1.08; 95% confidence interval, 1.03-1.13; P<0.01), and pulmonary vascular
      resistance (hazard ratio, 1.01; 95% confidence interval, 1.00-1.01; P=0.03) were
      significantly associated with cardiac events. Patients with T1 times below the
      median (<388.3 ms) were at greater risk of cardiac events than the rest of the
      group (P<0.01). Extracellular matrix of left ventricular biopsies (n=9),
      quantified by TissueFAXS technology correlated with T1 time (R=0.98; P<0.01). T1
      time also correlated with right ventricular-pulmonary arterial coupling
      (pulmonary vascular resistance: R=-0.36; P<0.01; right ventricular ejection
      fraction: R=0.28; P=0.01). CONCLUSIONS: In the present preliminary study, cardiac
      magnetic resonance postcontrast T1 time is associated with prognosis in HFPEF,
      suggesting postcontrast T1 as possible biomarker for HFPEF.

PMID- 24036387
TI  - Valvuloarterial impedance, but not aortic stenosis severity, predicts syncope in
      patients with aortic stenosis.
AB  - BACKGROUND: The presence of syncope in patients with aortic valve stenosis (AS)
      predicts a grave prognosis. However, the evaluation of AS severity has been
      limited to valve-specific factors such as aortic valve area and mean transaortic
      pressure gradient. Recently, valvuloarterial impedance (Zva) was proposed for the
      estimation of global left ventricular afterload. Therefore, because predictors of
      syncope in patients with AS have not been investigated in recent years, we
      assessed the effect of clinical characteristics and echocardiographic parameters,
      including Zva, on syncope in patients with AS. METHODS AND RESULTS: We
      retrospectively studied 451 patients with moderate and severe AS without low left
      ventricular ejection fraction (<40%). Patients with syncope (n=79; 18%) had
      higher Zva (5.1+/-0.9 versus 4.4+/-0.9 mm Hg/mL per m(2); P<0.001) than those
      without (n=372; 82%). However, no significant differences existed in the mean
      transaortic pressure gradient (P=0.076) or the aortic valve area (P=0.160)
      between the 2 groups. In the multivariable analysis, only Zva was an independent
      predictor of syncope in patients with AS (odds ratio, 2.02; 95% confidence
      interval, 1.54-2.64; P<0.001). However, systolic blood pressure, relative wall
      thickness, the early transmitral flow velocity to peak early diastolic mitral
      annular velocity ratio, and mean transaortic pressure gradient were not
      identified as independent predictors. Receiver operating characteristic curve
      analysis identified Zva >=4.7 mm Hg/mL per m(2) as the cutoff value associated
      with syncope in patients with AS. CONCLUSIONS: Our study suggests that high Zva,
      but not conventional parameters of AS, identifies AS patients with an increased
      risk of syncope.

PMID- 24036388
TI  - Ocular silicon distribution and clearance following intravitreal injection of
      porous silicon microparticles.
AB  - Porous silicon (pSi) microparticles have been investigated for intravitreal drug
      delivery and demonstrated good biocompatibility. With the appropriate surface
      chemistry, pSi can reside in vitreous for months or longer. However, ocular
      distribution and clearance pathway of its degradation product, silicic acid, are
      not well understood. In the current study, rabbit ocular tissue was collected at
      different time point following fresh pSi (day 1, 5, 9, 16, and 21) or oxidized
      pSi (day 3, 7, 14, 21, and 35) intravitreal injection. In addition, dual-probe
      simultaneous microdialysis of aqueous and vitreous humor was performed following
      a bolus intravitreal injection of 0.25 mL silicic acid (150 MUg/mL) and six
      consecutive microdialysates were collected every 20 min. Silicon was quantified
      from the samples using inductively coupled plasma-optical emission spectroscopy.
      The study showed that following the intravitreal injection of oxidized pSi, free
      silicon was consistently higher in the aqueous than in the retina (8.1 +/- 6.5
      vs. 3.4 +/- 3.9 MUg/mL, p = 0.0031). The area under the concentration-time curve
      (AUC) of the retina was only about 24% that of the aqueous. The mean residence
      time was 16 days for aqueous, 13 days for vitreous, 6 days for retina, and 18
      days for plasma. Similarly, following intravitreal fresh pSi, free silicon was
      also found higher in aqueous than in retina (7 +/- 4.7 vs. 3.4 +/- 4.1 MUg/mL, p
      = 0.014). The AUC for the retina was about 50% of the AUC for the aqueous. The
      microdialysis revealed the terminal half-life of free silicon in the aqueous was
      30 min and 92 min in the vitreous; the AUC for aqueous accounted for 38% of the
      AUC for vitreous. Our studies indicate that aqueous humor is a significant
      pathway for silicon egress from the eye following intravitreal injection of pSi
      crystals. 

PMID- 24036389
TI  - Space representation in children with dyslexia and children without dyslexia:
      contribution of line bisection and circle centering tasks.
AB  - Line bisection tasks (different space locations and different line lengths) and
      circle centering tasks (visuo-proprioceptive and proprioceptive explorations,
      with left or right starting positions) were used to investigate space
      representation in children with dyslexia and children without dyslexia. In line
      bisection, children with dyslexia showed a significant rightward bias for central
      and right-sided locations and a leftward bias for left-sided location.
      Furthermore, the spatial context processing was asymmetrically more efficient in
      the left space. In children without dyslexia, no significant bias was observed in
      central lines but the spatial context processing was symmetrical in both spaces.
      When the line length varied, no main effect was shown. These results strengthen
      the 'inverse pseudoneglect' hypothesis in dyslexia. In the lateral dimension of
      the circle centering tasks, children showed a response bias in the direction of
      the starting hand location for proprioceptive condition. For radial dimension,
      the children showed a forward bias in visuo-proprioceptive condition and more
      backward error in proprioceptive condition. Children with dyslexia showed a
      forward bias in clockwise exploration and more accurate performance in
      counterclockwise exploration for left starting position which may be in
      accordance with leftward asymmetrical spatial context processing in line
      bisection. These results underline the necessity to use the line bisection task
      with different locations as an appropriate experimental paradigm to study lateral
      representational bias in dyslexia. The contribution of the present results in the
      understanding of space representation in children with dyslexia and children
      without dyslexia is discussed in terms of attentional processes and
      neuroanatomical substrate. 

PMID- 24036390
TI  - A physical fitness follow-up in children with cerebral palsy receiving 12-week
      individualized exercise training.
AB  - Physical fitness in children with cerebral palsy (CP) is lower than in their
      peers. A 12-week individualized home-based exercise program completed by 11
      children with CP 10 years earlier showed a favorable effect on physical fitness
      performance. We follow-up the physical fitness of those 11 children with CP, and
      compare their physical fitness and health-related quality of life (HRQoL) to
      children with CP without exercise training matched with age and motor levels.
      Eleven children with CP in the 2003 program as a follow-up group (FUG) and 12
      volunteers recruited as a control group (CG) participated in this study. Physical
      fitness measures, including cardiopulmonary endurance, muscle strength, body mass
      index (BMI), flexibility, agility, balance, and the SF-36 Taiwan version, were
      assessed in both groups. After 10 years, the FUG showed better physical fitness
      in cardiopulmonary endurance and muscle strength (p<.05). Compared to the CG, the
      FUG demonstrated better muscle strength, agility, and balance (p<.05). However,
      the HRQoL did not show a significant difference between the FUG and the CG.
      Individualized home-based exercise training is beneficial for children with CP.
      Over 10 years, the FUG was more devoted to physical activity than was the CG.
      Physical exercise may not directly affect the HRQoL in this study.

PMID- 24036391
TI  - Complete (1)H and (13)C NMR chemical shift assignments of mono- to
      tetrasaccharides as basis for NMR chemical shift predictions of oligosaccharides
      using the computer program CASPER.
AB  - (1)H and (13)C NMR chemical shift data are used by the computer program CASPER to
      predict chemical shifts of oligo- and polysaccharides. Three types of data are
      used, namely, those from monosaccharides, disaccharides, and trisaccharides. To
      improve the accuracy of these predictions we have assigned the (1)H and (13)C NMR
      chemical shifts of eleven monosaccharides, eleven disaccharides, twenty
      trisaccharides, and one tetrasaccharide; in total 43 compounds. Five of the
      oligosaccharides gave two distinct sets of NMR resonances due to the alpha- and
      beta-anomeric forms resulting in 48 (1)H and (13)C NMR chemical shift data sets.
      In addition, the pyranose ring forms of Neu5Ac were assigned at two temperatures,
      due to chemical shift displacements as a function of temperature. The (1)H NMR
      chemical shifts were refined using total line-shape analysis with the PERCH NMR
      software. (1)H and (13)C NMR chemical shift predictions were subsequently carried
      out by the CASPER program (http://www.casper.organ.su.se/casper/) for three
      branched oligosaccharides having different functional groups at their reducing
      ends, namely, a mannose-containing pentasaccharide, and two fucose-containing
      heptasaccharides having N-acetyllactosamine residues in the backbone of their
      structures. Good to excellent agreement was observed between predicted and
      experimental (1)H and (13)C NMR chemical shifts showing the utility of the method
      for structural determination or confirmation of synthesized oligosaccharides. 

PMID- 24036392
TI  - Differential O-3/O-4 selectivity in the glycosylation of N-dimethylmaleoyl
      protected hexosamine acceptors: effect of a conformationally armed (superarmed)
      glycosyl donor.
AB  - An assessment of the relative O-3/O-4 reactivities of both alpha- and beta-methyl
      glycosides of N-dimethylmaleoyl (DMM) glucosamine and allosamine acceptors
      protected at O-6 with a benzyl group using a d-glucopyranosyl conformationally
      armed donor (superarmed donor) counterpart is presented. The glycosylation of
      glucosamine derivatives followed the trends already observed for disarmed donors.
      On the other hand, the glycosylation of allosamine derivatives gave exclusively
      substitution on the equatorial O-4, in spite that with a disarmed donor the point
      of substitution is exclusively on the more hindered, electronically-preferred O
      3. 

PMID- 24036393
TI  - Functional analysis of the seed coat-specific gene GbMYB2 from cotton.
AB  - MYB transcription factors are essential for cotton fiber development. We isolated
      the R2R3-MYB gene GbMYB2 from Gossypium barbadense. RNA in situ hybridization
      analysis showed that GbMYB2 is mainly expressed in the outer integuments of
      cotton ovules and in elongating fibers. GbMYB2 expression increased throughout
      fiber initiation and during the elongation stage. The expression level of GbMYB2
      was higher in the Gossypium hirsutum cultivar Xu142 than in the Xu142 (fl)
      mutant. Overexpression of GbMYB2 in Arabidopsis caused thicker leaf trichomes and
      longer roots to develop due to the activation of trichome development-related
      genes such as GL2. These results indicate that GbMYB2 is an R2R3-MYB gene that is
      involved in fiber development. 

PMID- 24036394
TI  - Molecular characterization of Glycine max squalene synthase genes in seed
      phytosterol biosynthesis.
AB  - The reaction catalyzed by squalene synthase (EC.2.5.1.21) that converts two
      molecules of farnesyl pyrophosphate to squalene represents a crucial branch point
      of the isoprenoid pathway in diverting carbon flux towards the biosynthesis of
      sterols. In the present study two soybean squalene synthase genes, GmSQS1 and
      GmSQS2, were identified in the soybean genome and functionally characterized for
      their roles in sterol biosynthesis. Both genes encode a deduced protein of 413
      amino acids. Complementation assays showed that the two genes were able to
      convert yeast sterol auxotrophy erg9 mutant to sterol prototrophy. Expression of
      GmSQS1 and GmSQS2 was ubiquitous in roots, stem, leaves, flower and young seeds
      of soybean, however GmSQS1 transcript was preferential in roots while GmSQS2
      transcript was more in leaves. Their expression was lower in response to
      dehydration treatments suggesting they might be negative regulators of water
      stress adaptation. Transgenic Arabidopsis plants overexpressing GmSQS1 driven by
      either constitutive or seed-specific promoters showed increases in the major end
      product sterols: campesterol, sitosterol and stigmasterol, which resulted in up
      to 50% increase in total sterol content in the seeds. The increase in the end
      product sterols by GmSQS1 overexpression was at the level achievable by
      previously reported overexpression of individual or combination of other key
      enzymes in the sterol pathway. Together the data demonstrate that soybean SQS
      genes play an important role in diverting carbon flux to the biosynthesis of the
      end product sterols in the seeds. 

PMID- 24036395
TI  - Influence of mitochondrion-toxic agents on the cardiovascular system.
AB  - Cardiovascular disease may be induced or worsened by mitochondrion-toxic agents.
      Mitochondrion-toxic agents may be classified as those with or without a clinical
      effect, those which induce cardiac disease only in humans or animals or both, as
      prescribed drugs, illicit drugs, exotoxins, or nutritiants, as those which affect
      the heart exclusively or also other organs, as those which are effective only in
      patients with a mitochondrial disorder or cardiac disease or also in healthy
      subjects, or as solid, liquid, or volatile agents. In humans, cardiotoxic agents
      due to mitochondrial dysfunction include anthracyclines (particularly
      doxorubicin), mitoxantrone, cyclophosphamide, cisplatin, fluorouracil, imatinib,
      bortezomib, trastuzumab, arsenic trioxide, cyclosporine-A, zidovudine,
      lamotrigine, glycosides, lidocain, isoproterenol, nitroprusside, pivalic acid,
      alcohol, cocaine, pesticides, cadmium, mycotoxins, cyanotoxins, meat meal, or
      carbon monoxide. Even more agents exhibit cardiac abnormalities due to
      mitochondrion-toxicity only in animals or tissue cultures. The mitochondrion
      toxic effect results from impairment of the respiratory chain, the oxidative
      phosphorylation, the Krebs cycle, or the beta-oxidation, from decrease of the
      mitochondrion-membrane potential, from increased oxidative stress, reduced anti
      oxidative capacity, or from induction of apoptosis. Cardiac abnormalities induced
      via these mechanisms include cardiomyopathy, myocarditis, coronary heart disease,
      arrhythmias, heart failure, or Takotsubo syndrome. Discontinuation of the
      cardiotoxic agent results in complete recovery in the majority of the cases.
      Antioxidants and nutritiants may be of additional help. Particularly coenzyme-Q,
      riboflavin, vitamin-E, vitamin-C, L-carnitine, vitamin-D, thiamin, folic acid,
      omega-3 fatty acids, and D-ribose may alleviate mitochondrial cardiotoxic
      effects.

PMID- 24036396
TI  - Estradiol and striatal dopamine receptor antagonism influence memory system bias
      in the female rat.
AB  - Estradiol (E2) has been shown to influence learning and memory systems used by
      female rats to find a reward. Rats with high levels of E2 tend to use
      allocentric, or place, memory while rats with low levels of E2 use egocentric, or
      response, memory. It has been shown that systemic dopamine receptor antagonism
      interacts with E2 to affect which memory system is used. Here, dopamine
      antagonists were administered directly into either the dorsal striatum or nucleus
      accumbens to determine where in the brain this interaction takes place. Seventy
      four young adult, female, Sprague-Dawley rats were trained and tested in a
      modified plus-maze. All rats were ovariectomized, received a subcutaneous low E2
      implant, and were implanted with bilateral cannulae into either the dorsal
      striatum or the nucleus accumbens. Additionally, high E2 rats received daily
      injections of E2 in a sesame oil solution while low E2 rats received daily
      injections of vehicle. After reaching criterion levels of performance in a plus
      maze task, rats were administered microinjections of either a dopamine D1
      receptor (SCH 23390; 0.1 MUg/ml and 0.01 MUg/ml) or D2 receptor (raclopride; 2
      MUg/ml and 0.5 MUg/ml) antagonist or a vehicle control (saline) in a
      counterbalanced manner. High E2 rats exhibited a trend towards a place memory
      bias while low E2 rats showed a response memory bias. Dorsal striatal
      administration of a D1, but not D2, dopamine receptor antagonist caused a switch
      in the memory system used by both high and low E rats. There was no significant
      effect of dopamine receptor antagonism in the nucleus accumbens group. Thus, E2
      determined which memory system controlled behavior in a plus-maze task. Moreover,
      this effect was modulated by dopamine D1R antagonism in the dorsal but not
      ventral striatum suggesting that memory systems are, in part, mediated by E2 and
      dopamine in this region.

PMID- 24036397
TI  - Hippocampal alpha7-nicotinic cholinergic receptors modulate memory
      reconsolidation: a potential strategy for recovery from amnesia.
AB  - When subjects are exposed to new learning experiences, the novel information
      could be acquired and eventually stored through memory consolidation process. The
      exposure of mice to a novel experience (a hole-board) after being trained in an
      inhibitory avoidance apparatus is followed by impaired performance of the
      avoidance memory in subsequent tests. The same impairing effect is produced when
      mice are exposed to the novel environment after the reactivation of the avoidance
      memory. This interfering effect is due to impaired consolidation or
      reconsolidation of the avoidance memory. The administration of the alpha7
      nicotinic receptor agonist choline (Ch) in the dorsal hippocampus (0.8
      MUg/hippocampus) immediately after the inhibitory avoidance memory reactivation,
      allowed memory recovery. This effect of Ch was time-dependent, and retention
      performance was not affected in drug-treated mice that were not subjected to
      memory reactivation, suggesting that the effects on performance are not due to
      non-specific effects of the drug. The effects of Ch also depended on the age of
      the reactivated memory. Altogether, our results suggest that Ch exerts its
      effects by modulating memory reconsolidation, and that the memory impairment
      induced by new learning is a memory expression failure and not a storage deficit.
      Therefore, reconsolidation, among other functions, might serve to change whether
      a memory will be expressed in later tests. Summarizing, our results open new
      avenues about the behavioral significance and the physiological functions of
      memory reconsolidation, providing new strategies for recovering memories from
      some types of amnesia.

PMID- 24036398
TI  - Divergent short- and long-term effects of acute stress in object recognition
      memory are mediated by endogenous opioid system activation.
AB  - Acute stress induces short-term object recognition memory impairment and elicits
      endogenous opioid system activation. The aim of this study was thus to evaluate
      whether opiate system activation mediates the acute stress-induced object
      recognition memory changes. Adult male Wistar rats were trained in an object
      recognition task designed to test both short- and long-term memory. Subjects were
      randomly assigned to receive an intraperitoneal injection of saline, 1 mg/kg
      naltrexone or 3 mg/kg naltrexone, four and a half hours before the sample trial.
      Five minutes after the injection, half the subjects were submitted to movement
      restraint during four hours while the other half remained in their home cages.
      Non-stressed subjects receiving saline (control) performed adequately during the
      short-term memory test, while stressed subjects receiving saline displayed
      impaired performance. Naltrexone prevented such deleterious effect, in spite of
      the fact that it had no intrinsic effect on short-term object recognition memory.
      Stressed subjects receiving saline and non-stressed subjects receiving naltrexone
      performed adequately during the long-term memory test; however, control subjects
      as well as stressed subjects receiving a high dose of naltrexone performed
      poorly. Control subjects' dissociated performance during both memory tests
      suggests that the short-term memory test induced a retroactive interference
      effect mediated through light opioid system activation; such effect was prevented
      either by low dose naltrexone administration or by strongly activating the opioid
      system through acute stress. Both short-term memory retrieval impairment and long
      term memory improvement observed in stressed subjects may have been mediated
      through strong opioid system activation, since they were prevented by high dose
      naltrexone administration. Therefore, the activation of the opioid system plays a
      dual modulating role in object recognition memory.

PMID- 24036399
TI  - An update on the current and future demand for care of pelvic floor disorders in
      the United States.
AB  - OBJECTIVE: In 2001, we predicted a 45% increase in the demand for care of women
      with pelvic floor disorders (PFDs) between 2000 and 2030. However, in 2010, we
      observed that in our clinic demand for care had increased substantially more than
      expected. Using updated data, we sought to provide more accurate projections of
      future demand for care of pelvic floor disorders in the United States. STUDY
      DESIGN: Demographic data on all new female patients between 30 and 89 years of
      age seen for pelvic floor disorders in our Urogynecology Clinic between 2009 and
      2011 were analyzed. These data were combined with United States Census Bureau
      projections for 2010 and 2030 stratified by 10-year age blocks. RESULTS: In 2010,
      our clinic saw a 116% increase in new patients per year compared with 2000. There
      was an 85% increase in new patient visits per 1000 women per year compared with
      2000. We estimate that 1,218,371 new patient visits took place in the United
      States in 2010 and predict 1,644,804 visits will occur in 2030. CONCLUSION: If
      the United States population increases 24% by 2030 as projected by the United
      States Census Bureau, we predict the demand for care for pelvic floor disorders
      will increase by 35% between 2010 and 2030. This new, more accurate projection
      for 2030 is based on improved baseline data from 2010 and is 72% higher than we
      predicted in 2000. Accurately quantifying this growing demand for care of pelvic
      floor disorders is important for public health planning and physician training.

PMID- 24036400
TI  - Placental pathology suggesting that preeclampsia is more than one disease.
AB  - OBJECTIVE: Our purpose was to evaluate the placental pathology in women with
      preeclampsia occurring at varying gestational ages. STUDY DESIGN: This was a
      secondary analysis of a prospective observational study of placentas from
      prespecified complicated pregnancies routinely submitted for standardized
      examination. For this study, a database of placental diagnoses from liveborn
      singleton gestations without major malformations was linked to a computerized
      obstetric database. The rates of standardized placental findings including
      vascular (atherosis, infarction) and nonvascular (hyperplasia) changes were
      evaluated according to gestational age at diagnosis of preeclampsia. RESULTS:
      Between Jan. 1, 2001, and Sept. 30, 2007, a total of 7122 women with pregnancies
      complicated by preeclampsia were delivered at our hospital. Of these, 1210 (17%)
      had placental examinations. Within this cohort, 209, 355, and 646 women were
      diagnosed with preeclampsia at gestations of 24(0/67) to 33(6/7), 34(0/7) to
      36(6/7), and 37(0/7) weeks or longer, respectively. Placental findings revealed
      hypoplasia was significantly associated with preeclampsia early in the third
      trimester, and histological evidence of placental vascular lesions was
      significantly increased at gestations of 24(0/67) to 33(6/7) weeks (53%) compared
      with 34% and 26% at 34(0/7) to 36(6/7) and 37 weeks or longer, respectively (P <
      .001). CONCLUSION: The placentas of women with preeclampsia onset before 34
      weeks' gestation were significantly different from those with preeclampsia at
      term. The former group demonstrated placental findings predominantly consistent
      with insufficiency because of vascular abnormalities. Such differing placental
      findings support the hypothesis that preeclampsia is a different disease,
      depending on the gestational age at diagnosis.

PMID- 24036401
TI  - Nicotine treatment prolongs gestation and inhibits cervical ripening in pregnant
      rats.
AB  - OBJECTIVE: The aims of this study were to examine the effects of nicotine
      treatment on the length of gestation, on fetal outcome, on cervical ripening, and
      on uterine contractility during pregnancy in rats. STUDY DESIGN: Pregnant rats
      were treated with various concentrations of nicotine (0.25, 0.5, 1, 2 mg/kg/d,
      subcutaneously). Delivery times and fetal weights were obtained. Cervical
      collagen cross-links were assessed in vivo by collagen light-induced fluorescence
      (LIF), and cervical resistance to stretch was measured by in vitro extensibility
      tests. RESULTS: Delivery time is significantly (P = .002) prolonged after high
      dose nicotine treatments. There are no significant changes in pup weights and
      placenta weights after nicotine treatments. Cervical collagen LIF and
      extensibility progressively decrease throughout pregnancy in control rats.
      Nicotine-treated rats showed significant (P < .001) cervical resistance to
      stretch and higher LIF compared with the control rats. Nicotine treatment in
      vitro had little effect on uterine contractility. CONCLUSION: Nicotine exposure
      during pregnancy prolongs gestation and inhibits cervical ripening, possibly by
      suppression of a cholinergic antiinflammatory response.

PMID- 24036402
TI  - Paper gestational age wheels are generally inaccurate.
AB  - OBJECTIVE: To compare the estimated date of confinement of paper gestational
      wheels to the estimated date of confinement of APPs wheels using a standard last
      menstrual period. METHODS: Obstetric providers were asked for their gestational
      wheels. The last menstrual period was set at Jan. 1, 2013, and the estimated date
      of confinement obtained was compared with the estimated date of confinement of
      Oct. 8th if the pregnancy completed 280 days. The process was performed on 20
      electronic APPs downloadable to cell phones. The process was repeated for both
      for the leap year of 2012. RESULTS: Thirty-one paper wheels from a variety of
      sources were collected. Ten wheels (35%) were consistent with the standard
      pregnancy duration of 280 days. Among the wheels surveyed, the largest
      discrepancy was 4 days short of 280 days. Two wheels gave an estimated date of
      confinement that differed from each other by 7 days. Wheels from the same source
      did not agree with each other. Twenty electronic gestational age calculators were
      examined. All 20 gave an estimated date of confinement of Oct. 8 consistent with
      280 days. None of the paper gestational wheels but all of the APPs corrected for
      a leap year. CONCLUSION: In contrast to APPs gestational age calculators, the
      estimated date of confinement of the majority of paper wheels deviated from the
      standard pregnancy duration of 280 days. Precision in gestational age assessment
      is critical in a variety of clinical settings and heightened by the focus by
      payers and reporting agencies on elective deliveries before 39 weeks. The use of
      paper gestational age wheels should be abandoned.

PMID- 24036403
TI  - The NICHD Consecutive Pregnancies Study: recurrent preterm delivery by subtype.
AB  - OBJECTIVE: Attention for recurrent preterm delivery has primarily focused on
      spontaneous subtypes with less known about indicated preterm delivery. STUDY
      DESIGN: In a retrospective cohort of consecutive pregnancies among 51,086 women
      in Utah (2002-2010), binary relative risk regression was performed to examine the
      risk of preterm delivery (PTD; <37 weeks) in the second observed delivery by PTD
      in the first, adjusting for maternal age, race/ethnicity, prepregnancy body mass
      index, insurance, smoking, alcohol and/or drug use, and chronic disease. Analyses
      were also performed stratified by prior preterm delivery subtype: spontaneous,
      indicated, or no recorded indication. RESULTS: There were 3836 women who
      delivered preterm in the first observed pregnancy (7.6%), of which 1160 repeated
      in the second (30.7%). Rate of recurrent PTD was 31.6% for prior spontaneous,
      23.0% for prior indicated delivery, and 27.4% for prior elective delivery. Prior
      spontaneous PTD was associated with a relative risk (RR) of 5.64 (95% confidence
      interval [CI], 5.27-6.05) of subsequent spontaneous and RR of 1.61 (95% CI, 0.98
      2.67) of subsequent indicated PTD. Prior indicated PTD was associated with an RR
      of 9.10 (95% CI, 4.68-17.71) of subsequent indicated and RR of 2.70 (95% CI, 2.00
      3.65) of subsequent spontaneous PTD. CONCLUSION: Prior indicated PTD was strongly
      associated with subsequent indicated PTD and with increased risk for subsequent
      spontaneous PTD. Spontaneous PTD had the highest rate of recurrence. Some common
      pathways for different etiologies of preterm delivery are likely, and indicated
      PTD merits additional attention for recurrence risk.

PMID- 24036404
TI  - A flexible Bayesian hierarchical approach for analyzing spatial and temporal
      variation in the fecal corticosterone levels in birds when there is imperfect
      knowledge of individual identity.
AB  - Population cycles have long interested biologists. The ruffed grouse, Bonasa
      umbellus, is one such species whose populations cycle over most of their range.
      Thus, much effort has been expended to understand the mechanisms that might
      control cycles in this and other species. Corticosterone metabolites are widely
      used in studies of animals to measure physiological stress. We evaluated
      corticosterone metabolites in feces of territorial male grouse as a potential
      tool to study mechanisms governing grouse cycles. However, like most studies of
      corticosterone in wild animals, we did not know the identity of all individuals
      for which we had fecal samples. This presented an analytical problem that
      resulted in either pseudoreplication or confounding. Therefore, we derived an
      analytical approach that accommodated for uncertainty in individual
      identification. Because we had relatively low success capturing birds, we
      estimated turnover probabilities of birds on territorial display sites based on
      capture histories of a limited number of birds we captured. Hence, we developed a
      study design and modeling approach to quantify variation in corticosterone levels
      among individuals and through time that would be applicable to any field study of
      corticosterone in wild animals. Specifically, we wanted a sampling design and
      model that was flexible enough to partition variation among individuals, spatial
      units, and years, while incorporating environmental covariates that would
      represent potential mechanisms. We conducted our study during the decline phase
      of the grouse cycle and found high variation among corticosterone samples (11.33
      443.92 ng/g [x=113.99 ng/g, SD=69.08, median=99.03 ng/g]). However, there were
      relatively small differences in corticosterone levels among years, but levels
      declined throughout each breeding season, which was opposite our predictions for
      stress hormones correlating with a declining population. We partitioned the
      residual variation into site, bird, and repetition (i.e., multiple samples
      collected from the same bird on the same day). After accounting for years and
      three general periods within breeding seasons, 42% of the residual variation
      among observations was attributable to differences among individual birds. Thus,
      we attribute little influence of site on stress level of birds in our study, but
      disentangling individual from site effects is difficult because site and bird are
      confounded. Our model structures provided analytical approaches for studying
      species having different ecologies. Our approach also demonstrates that even
      incomplete information on individual identity of birds within samples is useful
      for analyzing these types of data.

PMID- 24036406
TI  - A history of smoking is associated with improved survival in patients treated
      with mild therapeutic hypothermia following cardiac arrest.
AB  - OBJECTIVES: To assess the association between smoking and survival with a good
      neurologic outcome in patients following cardiac arrest treated with mild
      therapeutic hypothermia (TH). METHODS: We conducted a retrospective observational
      study of a prospectively collected cohort of 188 consecutive patients following
      cardiac arrest treated with TH between May 2007 and January 2012. Smoking status
      was retrospectively collected via chart review and was classified as "ever" or
      "never". Primary endpoint was survival to hospital discharge with a good
      neurologic outcome and was compared between smokers and nonsmokers. Logistic
      regression analysis was used to assess the association between smoking status and
      neurologic outcome at hospital discharge; adjusting for age, initial rhythm, time
      to return of spontaneous circulation (ROSC), bystander CPR, and time to
      initiation of TH. RESULTS: Smokers were significantly more likely to survive to
      hospital discharge with good neurologic outcome compared to nonsmokers (50% vs.
      28%, p=0.003). After adjusting for age, initial rhythm, time to ROSC, bystander
      CPR, and time to initiation of TH, a history of smoking was associated with
      increased odds of survival to hospital discharge with good neurologic outcome (OR
      3.54, 95% CI 1.41-8.84, p=0.007). CONCLUSIONS: Smoking is associated with
      improved survival with good neurologic outcome in patients following cardiac
      arrest. We hypothesize that our findings reflect global ischemic conditioning
      caused by smoking.

PMID- 24036405
TI  - Electron microscopy analysis of a disaccharide analog complex reveals receptor
      interactions of adeno-associated virus.
AB  - Mechanistic studies of macromolecular complexes often feature X-ray structures of
      complexes with bound ligands. The attachment of adeno-associated virus (AAV) to
      cell surface glycosaminoglycans (GAGs) is an example that has not proven amenable
      to crystallography, because the binding of GAG analogs disrupts lattice contacts.
      The interactions of AAV with GAGs are of interest in mediating the cell
      specificity of AAV-based gene therapy vectors. Previous electron microscopy led
      to differing conclusions on the exact binding site and the existence of large
      ligand-induced conformational changes in the virus. Conformational changes are
      expected during cell entry, but it has remained unclear whether the electron
      microscopy provided evidence of their induction by GAG-binding. Taking advantage
      of automated data collection, careful processing and new methods of structure
      refinement, the structure of AAV-DJ complexed with sucrose octasulfate is
      determined by electron microscopy difference map analysis to 4.8A resolution. At
      this higher resolution, individual sulfate groups are discernible, providing a
      stereochemical validation of map interpretation, and highlighting interactions
      with two surface arginines that have been implicated in genetic studies.
      Conformational changes induced by the SOS are modest and limited to the loop most
      directly interacting with the ligand. While the resolution attainable will depend
      on sample order and other factors, there are an increasing number of
      macromolecular complexes that can be studied by cryo-electron microscopy at
      resolutions beyond 5A, for which the approaches used here could be used to
      characterize the binding of inhibitors and other small molecule effectors when
      crystallography is not tractable. 

PMID- 24036407
TI  - Availability and quality of cardiopulmonary resuscitation information for Spanish
      speaking population on the Internet.
AB  - BACKGROUND: Bystander cardiopulmonary resuscitation (CPR) is a vital link in the
      chain of survival for out-of-hospital cardiac arrest (OHCA); however, there are
      racial/ethnic disparities in the provision of bystander CPR. Approximately 32% of
      Hispanics perform CPR when confronted with cardiac arrest, whereas approximately
      41% of non-Hispanics perform CPR. Public education, via the Internet, may be
      critical in improving the performance of bystander CPR among Hispanics. The
      objective of this study was to evaluate the availability and quality of CPR
      related literature for primary Spanish-speaking individuals on the Internet.
      METHODS: Two search engines (Google and Yahoo!) and a video-site (YouTube) were
      searched using the following terms: "resucitacion cardiopulmonar" and
      "reanimacion cardiopulmonar." Inclusion criteria were: education of CPR
      technique. Exclusion criteria were: instruction on pediatric CPR technique,
      failure to provide any instruction on CPR technique, or duplicated website. Data
      elements were collected on the content and quality of the websites and videos,
      such as assessing scene safety, verifying responsiveness, activating EMS,
      properly positioning hands on chest, performing accurate rate and depth of
      compressions. RESULTS: Of the 515 websites or videos screened, 116 met criteria
      for inclusion. The majority of websites (86%; 95% Confidence Interval [CI] 79
      92%) educated viewers on traditional bystander CPR (primarily, 30:2 CPR), while
      only 14% (95% CI 9-21%) taught hands-only CPR. Of websites that used video
      (N=62), 84% were conducted in Spanish and 16% in English. The quality of CPR
      education was generally poor (median score of 3/6, IQR of 3.0). Only half of
      websites properly educated on how to check responsiveness, activate EMS and
      position hands on chest. Eighty-eight percent of websites failed to educate
      viewers on assessing scene safety. The majority of websites had improper or no
      education on both rate and depth of compressions (59% and 63%, respectively).
      Only 16% of websites included 5 or more quality markers for proper bystander CPR.
      CONCLUSIONS: A small proportion of internet resources have high quality CPR
      education for a Spanish-speaking population. More emphasis should be placed on
      improving the quality of educational resources available on the Internet for
      Spanish-speaking populations, and with particular emphasis on current basic life
      support recommendations.

PMID- 24036408
TI  - Simplified dispatcher instructions improve bystander chest compression quality
      during simulated pediatric resuscitation.
AB  - AIM: Cardiopulmonary resuscitation (CPR) quality is associated with survival
      outcomes after out-of-hospital cardiac arrest. The objective of this study was to
      evaluate the effectiveness of simplified dispatcher CPR instructions to improve
      the chest compression (CC) quality during simulated pediatric cardiac arrest in
      public places. METHODS: Adult bystanders recruited in public places were
      randomized to receive one of two scripted dispatcher CPR instructions: (1) "Push
      as hard as you can" (PUSH HARD) or (2) "Push approximately 2 inches" (TWO
      INCHES). A pediatric manikin with realistic CC characteristics (similar to a 6
      year-old child), and a CPR recording defibrillator was used for quantitative CC
      data collection during a 2-min simulated pediatric scenario. The primary outcome
      was average CC depth treated as a continuous variable. Secondary outcomes
      included compliance with American Heart Association (AHA) CPR targets. Analysis
      was by two-sided unpaired t-test and Chi-square test, as appropriate. RESULTS:
      128 out of 140 providers screened met inclusion/exclusion criteria and all 128
      consented. The average CC depth (mean (SEM)) was greater in PUSH HARD compared to
      TWO INCHES (43 (1) vs. 36 (1) mm, p<0.01) and met AHA targets more often (39%
      (25/64) vs. 20% (13/64), p=0.02). CC rates trended higher in the PUSH HARD group
      (93 (4) vs. 82 (4) CC/min, p=0.06). More providers did not achieve full chest
      recoil with PUSH HARD compared to TWO INCHES (53% (34/64) vs. 75% (48/64),
      p=0.01). CONCLUSIONS: Simplified dispatcher assisted pediatric CPR instructions:
      "Push as hard as you can" was associated with lay bystanders providing deeper and
      faster CCs on a simulated, 6-year-old pediatric manikin. However, percentage of
      providers leaning between CC increased. The potential effect of these simplified
      instructions in younger children remains unanswered.

PMID- 24036409
TI  - Optimal loop duration during the provision of in-hospital advanced life support
      (ALS) to patients with an initial non-shockable rhythm.
AB  - BACKGROUND: In advanced life support (ALS), time-cycled "loops" of chest
      compressions form the basis of action. However, the provider must compromise
      between interrupting compressions and detecting a change in cardiac rhythm. An
      "optimal" loop duration would best balance these choices. The current
      international CPR guidelines recommend 2-min loop durations. The aim of this
      study was to investigate the "optimal" loop duration in patients with initial
      asystole or pulseless electrical activity (PEA). MATERIALS AND METHODS: Detailed
      defibrillator recordings from 249 in-hospital cardiac arrests at the University
      of Chicago Medicine (Chicago, IL) and St. Olav University Hospital (Trondheim,
      Norway) were analysed. The clinical states of asystole, PEA, ventricular
      fibrillation/-tachycardia (VF/VT) and return of spontaneous circulation (ROSC)
      were annotated along the time axis. PEA and asystole were combined as a single
      state for the analysis of state development. The probability of staying in
      PEA/asystole over time was estimated non-parametrically. In addition, to
      distinguish between initial and secondary PEA/asystole, the latter was defined by
      the transition from VF/VT or ROSC. RESULTS: Among patients with initial PEA
      (n=179), 25% and 50% of patients had left PEA/asystole after 4 and 9 min of ALS
      efforts, respectively. The corresponding time points for patients with initial
      asystole (n=70) were 7.3 and 13.3 min, respectively. The probability of
      transition from secondary PEA/asystole to ROSC or VF/VT varied between 10% and
      20% in each 2-4 min interval. CONCLUSION: The "optimal" first loop duration may
      be 4 min in initial PEA and 6-8 min in initial asystole. If secondary
      PEA/asystole is encountered, 2-min loop duration seems appropriate.

PMID- 24036410
TI  - ViEWS in the emergency department.

PMID- 24036412
TI  - Fosinoprilat alleviates lipopolysaccharide (LPS)-induced inflammation by
      inhibiting TLR4/NF-kappaB signaling in monocytes.
AB  - OBJECTIVE: To evaluate the effect of the fosinoprilat on lipopolysacharides (LPS)
      induced inflammation in monocytes in vitro. METHODS: Human mononuclear THP1 cells
      were cultured in complete medium, treated with or without LPS and different
      concentrations (0,0.25,0.5,1,5,and 10MUmol/L) of fosinoprilat. Toll-like receptor
      (TLR4) mRNA expression was detected by real-time RT-PCR and TLR4 protein level on
      the surface of monocyte was determined by flow cytometry. Nuclear factor-kappa B
      (NF-kappaB) protein level was detected by Western blotting. Cultured supernatant
      of the THP1 cells in different groups were analyzed by ELISA to detect the levels
      of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF-alpha). RESULTS:
      Both the mRNA and surface protein level of the TLR4 in the THP1 cells were
      enhanced by the LPS treatment and down-regulated by pretreatment of the
      fosinoprilat. Accordingly, LPS-induced NF-kappaB protein was decreased by the
      fosinoprilat treatment. The increasing secretion of IL-1beta, IL-6 and TNF-alpha
      induced by LPS could also be attenuated by the fosinoprilat treatment.
      CONCLUSION: The inhibitory effect of the fosinoprilat on the TRL4/NF-kappaB
      signaling pathway reveals a potential anti-inflammatory and anti-atherosclerosis
      target.

PMID- 24036413
TI  - The two-step electrochemical oxidation of alcohols using a novel recombinant PQQ
      alcohol dehydrogenase as a catalyst for a bioanode.
AB  - A bioanode has been developed based on the oxidation of ethanol by the
      recombinant pyrroloquinoline quinone (PQQ) dependent alcohol dehydrogenase from
      Pseudomonas putidaKT2440 heterologously expressed in Pichia pastoris. The apo
      form of the recombinant protein (PpADH) was purified and displayed catalytic
      activity for binding PQQ in the presence of Ca(2+). PpADH exhibited broad
      substrate specificity towards various alcohols and aldehydes. The Km values for
      the aldehydes of PpADH were increased compared to those for the alcohols, whereas
      the kcat values were unaltered. For instance, the Km values at T=298.15K (25 
      degrees C) for ethanol and acetaldehyde were 0.21 (+/- 0.02)mM and 5.8 (+/-
      0.60)mM, respectively. The kcat values for ethanol and acetaldehyde were 24.8 (+/
      1.2) s(-1) and 31.1 (+/- 1.2) s(-1), respectively. The aminoferrocene was used
      as an electron transfer mediator between PpADH and the electrode during
      electrochemical experiments. The catalytic currents for the oxidation of alcohol
      and acetaldehyde by PpADH were also observed in this system. The electric charge
      for the oxidation of ethanol (Q = 2.09 * 10(-3) . C) was increased two-fold
      compared to that for the oxidation of acetaldehyde (Q = 0.95 * 10(-3) . C), as
      determined by chronoamperometric measurements. Thus, we have electrochemically
      demonstrated the two-step oxidation of ethanol to acetate using only PpADH.

PMID- 24036411
TI  - Bridging the interval: theory and neurobiology of trace conditioning.
AB  - An early finding in the behavioral analysis of learning was that conditioned
      responding weakens as the conditioned stimulus (CS) and unconditioned stimulus
      (US) are separated in time. This "trace" conditioning effect has been the focus
      of years of research in associative learning. Theoretical accounts of trace
      conditioning have focused on mechanisms that allow associative learning to occur
      across long intervals between the CS and US. These accounts have emphasized
      degraded contingency effects, timing mechanisms, and inhibitory learning. More
      recently, study of the neurobiology of trace conditioning has shown that even a
      short interval between the CS and US alters the circuitry recruited for learning.
      Here, we review some of the theoretical and neurobiological mechanisms underlying
      trace conditioning with an emphasis on recent studies of trace fear conditioning.
      Findings across many studies have implications not just for how we think about
      time and conditioning, but also for how we conceptualize fear conditioning in
      general, suggesting that circuitry beyond the usual suspects needs to be
      incorporated into current thinking about fear, learning, and anxiety. 

PMID- 24036414
TI  - Oldest fruits of the grape family (Vitaceae) from the Late Cretaceous Deccan
      cherts of India.
AB  - PREMISE OF THE STUDY: Despite the inferred Cretaceous origin of the Vitaceae,
      fossils of the grape family are relatively young, with the oldest previously
      known examples limited to the Paleocene of Europe and North America. New fossil
      evidence indicates that the family was already present in India in the Late
      Cretaceous (Maastrichtian), about 10-15 million years before the tectonic
      collision of India with Eurasia. * METHODS: Fruits and seeds were investigated by
      serial sections and peels of chert from the Deccan Intertrappean beds of central
      India, and compared anatomically with those of extant genera. * KEY RESULTS:
      Indovitis chitaleyae gen. et sp. n. is described based on immature fruits bearing
      four to six seeds, and isolated mature seeds. The seeds possess paired ventral
      infolds and a dorsal chalaza, features diagnostic of the order Vitales.
      Characters of chalaza shape, infold morphology, and seed coat anatomy place I.
      chitaleyae within Vitaceae and favor a phylogenetic position either sister to the
      Vitis-Ampelocissus clade or sister to the Ampelopsis-Clematicissus-Rhoicissus
      clade. * CONCLUSIONS: Presence of the oldest known vitaceous fossils in the
      latest Cretaceous of India indicates a previously undocumented Gondwanan history
      and a possible southern hemisphere origin for the Vitales. An "out-of-India"
      scenario might explain the relatively sudden appearance of diverse Vitaceae in
      the Late Paleocene and Early Eocene of the Northern Hemisphere.

PMID- 24036415
TI  - Neurovascular abnormalities in humans and mice with Huntington's disease.
AB  - Cerebral microvascular aberrations have recently become recognized as a source of
      pathologies in neurodegenerative disorders, but this concept has not been fully
      examined with respect to Huntington's disease (HD). A novel in vivo technique,
      three-dimensional microscopic magnetic resonance angiography (MUMRA), allows
      visualization of the neurovascular system in exquisite detail and provides
      quantitative structural and functional information. This technique was applied in
      the present study, in parallel with immunohistological analysis and behavioral
      assessment, to a well-characterized mouse model of HD (R6/2). Dynamic contrast
      enhanced magnetic resonance imaging was used to examine the integrity of the
      blood-brain barrier (BBB). The MUMRA findings revealed an increase in vessel
      volume fraction and cerebral blood volume in the brains of R6/2 mice at the age
      of 7weeks when no apparent motor dysfunction was detected. Collagen IV
      immunostaining disclosed an enhancement in vessel density, but not in vessel size
      of the microvasculature in the mouse HD brain. This change in neurovasculature
      worsened with disease progression, with no apparent disruption in the BBB. Most
      importantly, immunohistological assays of human tissues revealed that the vessel
      densities in the cortex, caudate/putamen, and substantia nigra were higher in HD
      patients than in non-HD human subjects. The early onset of such vessel
      aberrations could be used as a biomarker for the early diagnosis of HD. 

PMID- 24036418
TI  - Speeding up the screening of steroids in urine: development of a user-friendly
      library.
AB  - This work presents a novel database search engine - MLibrary - designed to assist
      the user in the detection and identification of androgenic anabolic steroids
      (AAS) and its metabolites by matrix assisted laser desorption/ionization (MALDI)
      and mass spectrometry-based strategies. The detection of the AAS in the samples
      was accomplished by searching (i) the mass spectrometric (MS) spectra against the
      library developed to identify possible positives and (ii) by comparison of the
      tandem mass spectrometric (MS/MS) spectra produced after fragmentation of the
      possible positives with a complete set of spectra that have previously been
      assigned to the software. The urinary screening for anabolic agents plays a major
      role in anti-doping laboratories as they represent the most abused drug class in
      sports. With the help of the MLibrary software application, the use of MALDI
      techniques for doping control is simplified and the time for evaluation and
      interpretation of the results is reduced. To do so, the search engine takes as
      input several MALDI-TOF-MS and MALDI-TOF-MS/MS spectra. It aids the researcher in
      an automatic mode by identifying possible positives in a single MS analysis and
      then confirming their presence in tandem MS analysis by comparing the
      experimental tandem mass spectrometric data with the database. Furthermore, the
      search engine can, potentially, be further expanded to other compounds in
      addition to AASs. The applicability of the MLibrary tool is shown through the
      analysis of spiked urine samples. 

PMID- 24036416
TI  - Minocycline plus N-acetylcysteine synergize to modulate inflammation and prevent
      cognitive and memory deficits in a rat model of mild traumatic brain injury.
AB  - Traumatic brain injury (TBI) differs in severity from severe to mild. This study
      examined whether a combination of the drugs minocycline (MINO) plus N
      acetylcysteine (NAC) produces behavioral and histological improvements in a mild
      version of the controlled cortical impact model of TBI (mCCI). Following mCCI,
      rats acquired an active place avoidance task by learning the location of a
      stationary shock zone on a rotating arena. Rats acquired this task with a
      training protocol using a 10-minute intertrial interval. Mildly injured rats had
      an apparent deficit in long-term memory since they did not acquire the task when
      the intertrial interval was increased to 24 h. Mildly injured rats also had an
      apparent deficit in set shifting since, after successfully learning one shock
      zone location they did not learn the location of a second shock zone. MINO plus
      NAC synergistically limited these behavioral deficits in long-term memory and set
      shifting. mCCI also produced neuroinflammation at the impact site and at distal
      white matter tracts including the corpus callosum. At the impact site, MINO plus
      NAC attenuated CD68-expressing phagocytic microglia without altering neutrophil
      infiltration or astrocyte activation. The drugs had no effect on astrocyte
      activation in the corpus callosum or hippocampus. In the corpus callosum, MINO
      plus NAC decreased CD68 expression yet increased overall microglial activation as
      measured by Iba-1. MINO plus NAC acted synergistically to increase Iba-1
      expression since MINO alone suppressed expression and NAC alone had no effect.
      Despite the known anti-inflammatory actions of the individual drugs, MINO plus
      NAC appeared to modulate, rather than suppress neuroinflammation. This modulation
      of neuroinflammation may underlie the synergistic improvement in memory and set
      shifting by the drug combination after mCCI.

PMID- 24036419
TI  - The effects of stress hormones on growth of selected periodontitis related
      bacteria.
AB  - The focus of this study was to examine in vitro the effects of stress hormones
      (catecholamines: epinephrine, norepinephrine, dopamine and hydrocortisone:
      cortisol) on the growth of four anaerobic species of periodontitis-related
      bacteria (Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella
      intermedia and Tannerella forsythia) and one facultative anaerobic species
      (Eikenella corrodens). Bacterial growth was determined by two different methods:
      fluorescence in situ hybridization (FISH), and the viable count by culture
      method. To simulate stress, each single strain was grown in a special growth
      medium with three different concentrations of each hormone, using an anaerobic
      chamber at 37  degrees C. Growth of F. nucleatum increased in the presence of all
      stress hormones. Growth of P. gingivalis was not significantly influenced by any
      hormone. Growth of P. intermedia and E. corrodens was inhibited by almost all
      stress hormones tested. Both methods of analysis revealed that the highest
      concentrations of norepinephrine and cortisol increased the growth of T.
      forsythia. Different hormones have a different effect on the growth of
      periodontitis-related bacteria in vitro. It appears that bacterial viability is
      more strongly influenced than is bacterial metabolic activity. The growth of F.
      nucleatum particularly and partially of T. forsythia is increased by several
      stress hormones and may have an additional negative impact on periodontal
      disease.

PMID- 24036420
TI  - Clostridium novyi, sordellii, and tetani: mechanisms of disease.
AB  - Clostridia represent a diverse group of spore-forming gram positive anaerobes
      that include several pathogenic species. In general, diseases caused by
      clostridia are a result of intoxication of the infected host. Thus, clostridial
      toxins have been targeted for diagnostic, therapeutic, and preventive strategies
      against infection. Studying the mechanisms of action of clostridial toxins has
      not only shed light on the pathogenesis of infection but has provided important
      new insights into cell biology and immunology. A primary purpose of this
      manuscript is to provide a succinct review on the mechanisms of disease caused by
      intoxication by the pathogens Clostridium tetani, Clostridium novyi, and
      Clostridium sordellii. 

PMID- 24036421
TI  - Cloning and characterization of l-lactate dehydrogenase gene of Staphylococcus
      aureus.
AB  - Staphylococcus aureus a natural inhabitant of nasopharyngeal tract survives in
      the host as biofilms. In the present study S. aureus ATCC12600 grown under
      anaerobic conditions showed biofilm units of 0.086 as compared to 0.07 when this
      pathogen grown in aerobic conditions with elevated lactate formation and the same
      was also observed with increased biofilm units of 0.06, 0.084 and 0.167 under
      0.05%, 0.1% and 0.15% glucose supplementation in BHI broth. The lactate
      dehydrogenase (LDH) gene which catalyzes the formation of lactate was cloned,
      sequenced (Accession Numbers: JN645813) and expressed in Escherichia coli
      DH5alpha. The pure recombinant LDH exhibited molecular weight of 34 kDa in SDS
      PAGE and the enzyme kinetics of recombinant enzyme was found to be in the
      direction of lactate to pyruvate Km of 2.03 +/- 0.025 MUM and Kcat of 1.69 +/-
      0.03/min and from pyruvate to lactate Km of 1.62 +/- 0.10 MUM and Kcat of 1.75 +/
      0.03/min. In the LDH gene sequence "LKDIMA" was found to be conserved in all
      Gram positive bacteria and in all human LDH isoforms even though only 39%
      sequence homology was observed with all human LDH isoforms. However, 92%
      structural homology was observed with all human LDH isoforms. The molecular
      docking of pyruvate and lactate to the LDH structure showed -10.298 for pyruvate
      while -9.297 for lactate indicating higher affinity of pyruvate compared to
      lactate which concurred with the elevated LDH kinetics and rate of biofilm units
      in anaerobic conditions.

PMID- 24036422
TI  - The effect of vacuum packaging, EDTA, oregano and thyme oils on the
      microbiological quality of chicken's breast.
AB  - The effect of ethylenediaminetetraacetate (EDTA), oregano (Origanum vulgare) and
      thyme (Thymus vulgaris) oils, on the chicken breast fillets was examined in this
      study. The chicken breast fillets were stored under vacuum packaging (VP), at 4
      +/- 0.5  degrees C for a period of 18 days. There were used the following
      treatments of chicken breast fillets: Air-packaged (AC, control samples), vacuum
      packaged (VPC, control samples), VP with EDTA solution 1.50% w/w (VPEC, control
      samples), VP with oregano oil 0.20% v/w (VP + O) and VP with thyme oil 0.20% v/w,
      (VP + T). The quality assessment for vacuum packaging of the product in
      accordance with the terms above and EDTA treatment, oregano and thyme oil was
      established by microbiological analyzes. The microbiological properties as the
      total viable counts on Plate Count Agar, after incubation for 2 days at 37 
      degrees C and coliform bacteria on Violet Red Bile Glucose agar incubated at 37 
      degrees C for 24 h, lactobacilli on Rogosa and Sharpe agar after incubation 48-78
      h at 37  degrees C in an aerobic atmosphere supplemented with carbon dioxide (5%
      CO2) and Pseudomonas aeruginosa on Pseudomonas Isolation agar (PIA, Oxoid, UK)
      after incubation at 48 h at 35  degrees C were monitored. The using of oregano,
      thyme oil and EDTA with combination of vacuum packaging has significant effects
      to reduction of all followed groups of microorganisms compared with control group
      without vacuum packaging and untreated control group. The natural preservatives
      can be used as alternatives to chemical additives which could extend the meat and
      meat products shelf life. The knowledge about them can have an important economic
      feedback by reducing losses attributed to spoilage and by allowing the products
      to reach distant and new markets. This study shows how using of natural
      antimicrobials can extend the shelf-life of the meat product. 

PMID- 24036423
TI  - Short term exposure to elevated levels of leptin reduces proximal tubule cell
      metabolic activity.
AB  - Leptin plays a pathophysiological role in the kidney, however, its acute effects
      on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in
      vitro, Western blot analysis identified that exposure to leptin increases the
      phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42 and the
      mammalian target of rapamycin (mTOR). Importantly leptin (0.05, 0.10, 0.25 and
      0.50 MUg/ml) significantly reduced the metabolic activity of PTCs, and
      significantly decreased protein content per cell. Investigation of the role of
      p44/42 and mTOR on metabolic activity and protein content per cell, demonstrated
      that in the presence of MAPK inhibitor U0126 and mTOR inhibitor Ku-63794, that
      the mTOR pathway is responsible for the reduction in PTC metabolic activity in
      response to leptin. However, p44/42 and mTOR play no role the reduced protein
      content per cell in OKs exposed to leptin. Therefore, leptin modulates metabolic
      activity in PTCs via an mTOR regulated pathway.

PMID- 24036425
TI  - Mechanistic implications for the chorismatase FkbO based on the crystal
      structure.
AB  - Chorismate-converting enzymes are involved in many biosynthetic pathways leading
      to natural products and can often be used as tools for the synthesis of chemical
      building blocks. Chorismatases such as FkbO from Streptomyces species catalyse
      the hydrolysis of chorismate yielding (dihydro)benzoic acid derivatives. In
      contrast to many other chorismate-converting enzymes, the structure and catalytic
      mechanism of a chorismatase had not been previously elucidated. Here we present
      the crystal structure of the chorismatase FkbO in complex with a competitive
      inhibitor at 1.08A resolution. FkbO is a monomer in solution and exhibits pseudo
      3-fold symmetry; the structure of the individual domains indicates a possible
      connection to the trimeric RidA/YjgF family and related enzymes. The co
      crystallised inhibitor led to the identification of FkbO's active site in the
      cleft between the central and the C-terminal domains. A mechanism for FkbO is
      proposed based on both interactions between the inhibitor and the surrounding
      amino acids and an FkbO structure with chorismate modelled in the active site. We
      suggest that the methylene group of the chorismate enol ether takes up a proton
      from an active-site glutamic acid residue, thereby initiating chorismate
      hydrolysis. A similar chemistry has been described for isochorismatases, albeit
      implemented in an entirely different protein scaffold. This reaction model is
      supported by kinetic data from active-site variants of FkbO derived by site
      directed mutagenesis. 

PMID- 24036424
TI  - The plant host can affect the encapsidation of brome mosaic virus (BMV) RNA: BMV
      virions are surprisingly heterogeneous.
AB  - Brome mosaic virus (BMV) packages its genomic and subgenomic RNAs into three
      separate viral particles. BMV purified from barley, wheat, and tobacco have
      distinct relative abundances of the encapsidated RNAs. We seek to identify the
      basis for the host-dependent differences in viral RNA encapsidation. Sequencing
      of the viral RNAs revealed recombination events in the 3' untranslated region of
      RNA1 of BMV purified from barley and wheat, but not from tobacco. However, the
      relative amounts of the BMV RNAs that accumulated in barley and wheat are similar
      and RNA accumulation is not sufficient to account for the difference in RNA
      encapsidation. Virions purified from barley and wheat were found to differ in
      their isoelectric points, resistance to proteolysis, and contacts between the
      capsid residues and the RNA. Mass spectrometric analyses revealed that virions
      from the three hosts had different post-translational modifications that should
      impact the physiochemical properties of the virions. Another major source of
      variation in RNA encapsidation was due to the purification of BMV particles to
      homogeneity. Highly enriched BMV present in lysates had a surprising range of
      sizes, buoyant densities, and distinct relative amounts of encapsidated RNAs.
      These results show that the encapsidated BMV RNAs reflect a combination of host
      effects on the physiochemical properties of the viral capsids and the enrichment
      of a subset of virions. The previously unexpected heterogeneity in BMV should
      influence the timing of the infection and also the host innate immune responses. 

PMID- 24036426
TI  - Chemical fingerprinting and phylogenetic mapping of saponin congeners from three
      tropical holothurian sea cucumbers.
AB  - Holothurians are sedentary marine organisms known to produce saponins (triterpene
      glycosides), secondary metabolites exhibiting a wide range of biological
      activities. In this paper, we investigated the saponin contents of semi-purified
      and membranolytic HPLC fractionated extracts from the body wall of three species
      of Holothuriidae as an attempt to examine its chemical diversity in relation to
      phylogenetic data. MALDI-FTICR MS and nano-HPLC-chip Q-TOF MS were used for mass
      profiling and isomer separation, respectively giving a unique chemical saponin
      fingerprint. Moreover, the methods used yield the highest number of congeners.
      However, saponin concentration, bioactivity and chemical diversity had no
      apparent relationship. MS fingerprint showed the presence of holothurinosides,
      which was observed for the first time in other Holothuria genera besides the
      basally positioned Holothuria forskali. This congener is proposed to be a
      primitive character that could be used for taxonomic purposes. The phylogenetic
      mapping also showed that the glycone part of the compound evolved from non
      sulfated hexaosides to sulfated tetraosides, which have higher membranolytic
      activity and hydrophilicity, the two factors affecting the total ecological
      activity (i.e. chemical defense) of these compounds. This might be an adaptation
      to increase the fitness of the organism.

PMID- 24036427
TI  - Identification and mRNA expression profile of glutamate receptor-like gene in
      quinclorac-resistant and susceptible Echinochloa crus-galli.
AB  - Animal ionotropic glutamate receptors (iGluRs) function as Ca(2+) ion channels
      during excitatory neurotransmission in nerve cells. Here, a glutamate receptor
      like gene (GLR) was identified and characterized from a plant - Echinochloa crus
      galli. The GLR gene was designated EcGLR1 with GenBank no: JX518597. It has a
      2,793 bp open reading frame predicted to encode a 101.7 kDa protein. Sequence
      alignment showed that EcGLR1 is a GLR homologue. Its expression in response to
      quinclorac treatment was assessed by real-time PCR in near-isogenic lines of
      quinclorac-resistant (R) and susceptible (S) biotypes of E. crus-galli. The
      expression of EcGLR1 in the seedling leaf and root at least increased 5 times in
      the S plants and 22 times in the R plants after exposure to quinclorac. In the
      adult plant leaves, roots and stems, its expression increased 11-14 times in the
      S plants and 23-25 times in the R plants after quinclorac stimulation. In the
      seed, its expression was 4 times less in the S plants than that in the R plants,
      but after treatment, the levels all increased by about 24 times in the two
      biotypes. EcGLR1 expression was 1-4 times greater in the R plants than in that in
      the S plants, and after treatment by quinclorac, the difference increased to a
      ratio of 4 to 9. Its expression was higher in all tissues tested of R biotypes
      than in that of S plants before or after quinclorac treatment. The results of
      this study provide basic information for the further research of function of the
      EcGLR1 in resistance to quinclorac in E. crus-galli.

PMID- 24036428
TI  - The switch role of the Tmod4 in the regulation of balanced development between
      myogenesis and adipogenesis.
AB  - Tmod4 (Tropomodulin 4) is a member of Tmod family that plays important role in
      thin filament length regulation and myofibril assembly. We found that the
      expression levels of Tmod4 were higher in skeletal muscle and adipose tissues.
      However, the function and regulation of the Tmod4 gene in the myogenesis and
      adipogenesis remains unclear. In this study, we found that the expression of
      Tmod4 was decreased in myogenesis while increased in adipogenesis. Then, the
      transcriptional regulation analysis of Tmod4 promoter showed that Tmod4 could be
      regulated directly by myogenic factors and adipogenic factors. Furthermore, the
      roles of Tmod4 in the myogenesis and adipogenesis were confirmed by its over
      expression in C2C12 cells and 3T3 cells, which suggested that Tmod4 could promote
      adipogenesis by up-regulating the adipogenic factors but moderately delay the
      myogenesis. These results indicated that the Tmod4 gene may play as a switch
      between myogenesis and adipogenesis, which resulted in the balanced development
      between skeletal muscle and adipose tissue. Therefore, the model for switch role
      of the Tmod4 in the balanced regulation between myogenesis and adipogenesis was
      proposed. It is showed that the expression of Tmod4 was activated in adipogenesis
      by adipogenic factors while inhibited in myogenesis by myogenic factors.
      Moreover, Tmod4 could promote adipogenesis by up-regulating the expression of
      adipogenic factors while moderately delaying the myogenesis. Our study provides
      an important basis for further understanding the regulation and function of
      porcine Tmod4 in muscle and fat development. 

PMID- 24036429
TI  - Three most common nonsynonymous UGT1A6*2 polymorphisms (Thr181Ala, Arg184Ser and
      Ser7Ala) and therapeutic response to deferiprone in beta-thalassemia major
      patients.
AB  - Deferiprone is used as a chelation agent in chronic iron overload in beta
      thalassemia patients. Patients on deferiprone therapy show variable response to
      this drug in terms of reduction in iron overload as well as adverse drug
      reactions (ADRs). The pharmacogenetic studies on deferiprone have not carried out
      in patients with blood disorders in India. Therefore, the present study was
      carried out to evaluate the three most common nonsynonymous UGT1A6 polymorphisms
      Thr181Ala (541 A/G), Arg184Ser (552 A/C) and Ser7Ala (19 T/G) and therapeutic
      response to deferiprone in beta-thalassemia major patients. Two hundred and
      eighty six (286) beta-thalassemia major patients were involved in the study.
      Serum ferritin levels were estimated periodically to assess the status of the
      iron overload and the patients were grouped into responders and non-responders
      depending on the ferritin levels. The UGT1A6 2 polymorphisms were detected by PCR
      RFLP methods. The association between the genotypes and outcome as well as ADRs
      was evaluated by Open EPI software. A significant difference was observed in the
      genotypic distribution of UGT1A6 2 Thr181Ala polymorphism in responders and non
      responders. However, there was no difference in the genotypic distribution
      between patients with and without ADRs. As far as the UGT1A6 2 Arg184Ser
      polymorphism is concerned, no significant difference was observed between
      responders and non-responders. Further, evaluating the association of UGT1A6 2
      Ser7Ala polymorphism with drug response, there was no significant difference in
      the genotypic distribution between responders and non-responders. However, there
      was a significant difference between responders with and without ADRs and non
      responders with and without ADRs. In addition to this haplotype analysis was also
      carried out. However, we did not find any specific haplotype to be significantly
      associated with the deferiprone response in beta-thalassemia major patients.

PMID- 24036430
TI  - Identification of novel target genes involved in Indian Fanconi anemia patients
      using microarray.
AB  - Fanconi anemia (FA) is a genetic disorder characterized by progressive bone
      marrow failure and a predisposition to cancers. Mutations have been documented in
      15 FA genes that participate in the FA-BRCA DNA repair pathway, a fundamental
      pathway in the development of the disease and the presentation of its
      characteristic symptoms. Certain symptoms such as oxygen sensitivity,
      hematological abnormalities and impaired immunity suggest that FA proteins could
      participate in or independently control other pathways as well. In this study, we
      identified 9 DNA repair genes that were down regulated in a genome wide analysis
      of 6 Indian Fanconi anemia patients. Functional clustering of a total of 233
      dysregulated genes identified key biological processes that included regulation
      of transcription, DNA repair, cell cycle and chromosomal organization. Microarray
      data revealed the down regulation of ATXN3, ARID4A and ETS-1, which were
      validated by RTPCR in a subsequent sample set of 9 Indian FA patients. Here we
      report for the first time a gene expression profile of Fanconi anemia patients
      from the Indian population and a pool of genes that might aid in the acquisition
      and progression of the FA phenotype.

PMID- 24036431
TI  - Prenatal diagnosis of de novo interstitial deletions involving 5q23.1-q23.3 and
      18q12.1-q12.3 by array CGH using uncultured amniocytes in a pregnancy with fetal
      interrupted aortic arch and atrial septal defect.
AB  - We present prenatal diagnosis of de novo interstitial deletions involving 5q23.1
      q23.3 and 18q12.1-q12.3 by aCGH using uncultured amniocytes in pregnancy with
      interrupted aortic arch and atrial septal defect in a fetus. The fetus
      postnatally manifested facial dysmorphisms and long slender fingers. We discuss
      the genotype-phenotype correlation and the consequence of haploinsufficiency of
      FBN2, DTNA and CELF4 in this case. 

PMID- 24036432
TI  - Isolation and expression profiling of GhNAC transcription factor genes in cotton
      (Gossypium hirsutum L.) during leaf senescence and in response to stresses.
AB  - NAC (NAM, ATAF, and CUC) is a plant-specific transcription factor family with
      diverse roles in plant development and stress regulation. In this report, stress
      responsive NAC genes (GhNAC8-GhNAC17) isolated from cotton (Gossypium hirsutum
      L.) were characterised in the context of leaf senescence and stress tolerance.
      The characterisation of NAC genes during leaf senescence has not yet been
      reported for cotton. Based on the sequence characterisation, these GhNACs could
      be classified into three groups belonging to three known NAC sub-families. Their
      predicted amino acid sequences exhibited similarities to NAC genes from other
      plant species. Senescent leaves were the sites of maximum expression for all
      GhNAC genes except GhNAC10 and GhNAC13, which showed maximum expression in
      fibres, collected from 25 days post anthesis (DPA) plants. The ten GhNAC genes
      displayed differential expression patterns and levels during natural and induced
      leaf senescence. Quantitative RT-PCR and promoter analyses suggest that these
      genes are induced by ABA, ethylene, drought, salinity, cold, heat, and other
      hormonal treatments. These results support a role for cotton GhNAC genes in
      transcriptional regulation of leaf senescence, stress tolerance and other
      developmental stages of cotton.

PMID- 24036433
TI  - Exposure and post-exposure effects of endosulfan on Bufo bufo tadpoles: morpho
      histological and ultrastructural study on epidermis and iNOS localization.
AB  - Endosulfan is a persistent organic pollutant (POP) that has lethal and sublethal
      effects on non-target organisms, including amphibians. In a laboratory study, we
      investigated direct and post-exposure effects of endosulfan on Bufo bufo
      tadpoles. For this purpose we exposed the tadpoles to a single short-term
      contamination event (96 h) at an environmentally-realistic concentration (200 MUg
      endosulfan/L). This was followed by a recovery period of 10 days when the
      experimental animals were kept in pesticide-free water. The endpoints were
      assessed in terms of mortality, incidence of deformity, effects on behavior, and
      the morpho-functional features of the epidermis. We found that a short-term
      exposure to the tested concentration of endosulfan did not cause mortality but
      induced severe sublethal effects, such as hyperactivity, convulsions, and axis
      malformations. Following relocation to a pesticide-free environment, we noted two
      types of response within the experimental sample, in terms of morphological and
      behavioral traits. Moreover, by using both ultrastructural and a morpho
      functional approach, we found that a short-term exposure to endosulfan negatively
      affected the amphibian epidermis. We also observed several histo-pathological
      alterations: increased mucous secretion, an increase in intercellular spaces and
      extensive cell degeneration, together with the induction of an inducible isoform
      of nitric oxide synthase (iNOS). Following the post-exposure period, we found
      large areas of epidermis in which degeneration phenomena were moderate or absent,
      as well as a further increase in iNOS immunoreactivity. Thus, after 10 days in a
      free-pesticide environment, the larval epidermis was able to partially replace
      elements that had been compromised due to a physiological and/or a pathological
      response to the pesticide. These results highlight the need for both exposure and
      post-exposure experiments, when attempting to assess pollutant effects.

PMID- 24036434
TI  - Toxic effects of the herbicide Roundup in the guppy Poecilia vivipara acclimated
      to fresh water.
AB  - Although it is believed that glyphosate-based herbicides are relatively nontoxic
      to humans, its broad use in agriculture and consequent contamination of aquatic
      systems is a concern. In the present study, reproductive (sperm quality) and
      biochemical parameters (acetylcholinesterase and glutathione S-transferase
      activity, lipoperoxidation, and antioxidant capacity against peroxyl radicals)
      were evaluated in adult guppies (Poecilia vivipara) acclimated to fresh water and
      exposed (96 h) to environmentally realistic concentrations of glyphosate (130 and
      700 MUg L(-1)) as the commercial formulation Roundup. Male guppies exposed to
      Roundup showed a poorer sperm quality, measured as reduced plasmatic membrane
      integrity, mitochondrial functionality, DNA integrity, motility, motility period
      and concentration of spermatic cells, than those kept under control condition (no
      Roundup addition to the water). Most of the spermatic parameters analyzed showed
      strong association to each other, which may help to understand the mechanisms
      underlying the observed reduction in sperm quality. Exposure to Roundup did not
      alter the biochemical parameters analyzed, though differences between genders
      were observed and deserve further investigations. Findings from the present study
      suggest that exposure to environmentally relevant concentrations of Roundup may
      negatively affect at long-term the reproduction of P. vivipara, with consequent
      changes in fish populations inhabiting environments contaminated with the
      herbicide.

PMID- 24036435
TI  - The immunological effects of oil sands surface waters and naphthenic acids on
      rainbow trout (Oncorhynchus mykiss).
AB  - There is concern surrounding the immunotoxic potential of naphthenic acids (NAs),
      a major organic constituent in waters influenced by oil sands contamination. To
      assess the immunological response to NAs, rainbow trout (Oncorhynchus mykiss)
      waterborne exposures were conducted with oil sands-influenced waters, NAs
      extracted and purified from oil sands tailings waters, and benzo[a]pyrene (BaP)
      as a positive control. After a 7d exposure, blood, spleen, head kidney, and gill
      samples were removed from a subset of fish in order to evaluate the distribution
      of thrombocytes, B-lymphocytes, myeloid cells, and T-lymphocytes using
      fluorescent antibodies specific for those cell types coupled with flow cytometry.
      The remaining trout in each experimental tank were injected with inactivated
      Aeromonas salmonicida and held in laboratory water for 21 d and subjected to
      similar lymphatic cell evaluation in addition to evaluation of antibody
      production. Fluorescent metabolites in bile as well as liver CYP1A induction were
      also determined after the 7 and 21 d exposure. Oil sands waters and extracted NAs
      exposures resulted in an increase in bile fluorescence at phenanthrene
      wavelengths, though liver CYP1A was not induced in those treatments as it was
      with the BaP positive control. Trout in the oil sands-influenced water exposure
      showed a decrease in B- and T-lymphocytes in blood as well as B-lymphocytes and
      myeloid cells in spleen and an increase in B-lymphocytes in head kidney. The
      extracted NAs exposure showed a decrease in thrombocytes in spleen at 8 mg/L and
      an increase in T-lymphocytes at 1mg/L in head kidney after 7d. There was a
      significant decrease in antibody production against A. salmonicida in both oil
      sands-influenced water exposures. Because oil sands-influenced waters affected
      multiple immune parameters, while extracted NAs impacts were limited, the NAs
      tested here are likely not the cause of immunotoxicity found in the oil sands
      influenced water.

PMID- 24036436
TI  - Electrochemical biosensors for biocontaminant detection consisting of carbon
      nanotubes, platinum nanoparticles, dendrimers, and enzymes.
AB  - The presented approach provides the advanced development of effective, rapid, and
      versatile electrochemical sensors for a small amount of analytes on potential,
      cheap, and disposable printed chips. The electrocatalytic activity of this
      biosensor revealed the feasible detection of hydrogen peroxide at low potential
      (~0.09 V) and the detection of a biocontaminant inhibitor (organophosphorus
      pesticide) in a wide range of concentrations. This efficiency comes from the
      chemical immobilization of catalysts (Pt nanoparticles) and electron transfer
      enlarging materials (carbon nanotubes) on an electrode. Especially, dendrimers
      raise the stable conjugation of enzymes (acetylcholinesterase/choline
      oxidase/peroxidase) as well as nanoparticles and carbon nanotubes on an
      electrode.

PMID- 24036437
TI  - An optimized method for extraction and quantification of nucleotides and
      nucleotide sugars from mammalian cells.
AB  - Glycosylation is a critical attribute of therapeutic proteins given its impact on
      the clinical safety and efficacy of these molecules. The biochemical process of
      glycosylation is inextricably dependent on metabolism and ensuing availability of
      nucleotides and nucleotide sugars (NSs) during cell culture. Herein, we present a
      comprehensive methodology to extract and quantify these metabolites from cultured
      cells. To establish the full protocol, two methods for the extraction of these
      compounds were evaluated for efficiency, and the requirement for quenching and
      washing the sample was assessed. A chromatographic method based on anion exchange
      has been optimized to separate and quantify eight nucleotides and nine NSs in
      less than 30 min. Degradation of nucleotides and NSs under extraction conditions
      was evaluated to aid in selection of the most efficient extraction protocol. We
      conclude that the optimized chromatographic method is quick, robust, and
      sensitive for quantifying nucleotides and NSs. Furthermore, our results show that
      samples taken from cell culture should be treated with 50% v/v acetonitrile and
      do not require quenching or washing for reliable extraction of nucleotides and
      NSs. This comprehensive protocol should prove useful in determining the impact of
      nucleotide and NS metabolism on protein glycosylation.

PMID- 24036438
TI  - Redefining parenthood: surviving the death of a child.
AB  - BACKGROUND: Although dying children are often aware of their impending death,
      parents are reluctant to communicate with their dying child about death.
      OBJECTIVE: The objective of this study was to examine how parents of children in
      the advanced stage of a life-threatening disease trajectory communicated about
      death. METHODS: Using grounded theory methods, data were collected via interviews
      with 18 parents of children who had died of an advanced life-threatening disease.
      RESULTS: Ways in which parents communicated with their dying child were impacted
      by the degree of threat to the parental role. From the onset of their child's
      life-threatening illness, the sense of parental self was threatened, resulting in
      "Parental Vulnerability." To endure parental vulnerability, parents confronted a
      process of "Redefining Parenthood." Before the child's death, parents experienced
      (1) Protecting From Fears, (2) Protecting Normalcy, (3) Protecting Faith, (4)
      Experiencing Protection From Their Child, and (5) Bookmarking Memories. After the
      child's death, parents experienced (1) Telling the Story, (2) Making Meaning, (3)
      Protecting the Child's Memory, (4) Defining a New Normal, and (5) Learning to
      Live With Regret. CONCLUSIONS: Results provide new information about the
      experiences of parents of dying children as they communicated with their child
      during the dying process and as they found ways to go on with life after their
      child's death. IMPLICATIONS FOR PRACTICE: Findings can be used by healthcare
      professionals to help support families of dying children. The field of pediatric
      oncology nursing would benefit from exploration of the dying child's perspective.

PMID- 24036439
TI  - Feasibility and acceptability of the patient-reported outcomes measurement
      information system measures in children and adolescents in active cancer
      treatment and survivorship.
AB  - BACKGROUND: Patient-reported outcomes related to symptoms, function, and quality
      of life during and following cancer treatment can guide care for pediatric cancer
      patients. To advance the science of patient-reported outcomes, the National
      Institutes of Health funded the Patient-Reported Outcomes Measurement Information
      System (PROMIS). OBJECTIVE: The objective of this study was to assess feasibility
      and acceptability of the PROMIS pediatric measures, as defined by enrollment and
      attrition rates as well as missingness by measure, item, participant, and
      assessment time point. METHODS: Eight- to 18-year-olds participated in 2 studies:
      PROMIS I, a cross-sectional study of children in active cancer treatment or
      survivorship, and PROMIS II, a longitudinal study with 3 assessment time points
      for children receiving curative treatment. RESULTS: PROMIS I (n = 200) and PROMIS
      II (n = 94) had enrollment rates of 92.5% and 89.7%, respectively. For PROMIS I,
      measure missingness was acceptable (8% missed any measures) and was not related
      to other study variables. For PROMIS II, measure missingness was minimal (0.8%),
      and item-level missingness was relatively low. In general, items that were
      skipped asked about experiences that participants had not encountered in the past
      7 days. CONCLUSIONS: In both studies, the PROMIS instruments demonstrated good
      feasibility and acceptability among pediatric cancer patients. Overall, we had
      high enrollment, low attrition, and acceptable rates of measure and item
      missingness. IMPLICATIONS FOR PRACTICE: Our results demonstrate that PROMIS
      measures are acceptable to 8- to 18-year-olds in different points of cancer care
      and feasible for use in pediatric cancer inpatient and outpatient settings.

PMID- 24036442
TI  - Synthesis and thermotropic studies of a new series of teraryl liquid crystals 2
      (4'-alkoxybiphen-4-yl)-5-cyanopyridines.
AB  - A new series of teraryl 2-(4'-alkoxybiphen-4-yl)-5-cyanopyridines (nO-PPPyCN, n =
      2-8) compounds, bearing a cyanopyridine terminus, were synthesized using a short
      2-step reaction with overall yields between 33% and 69%. Spectral analyses were
      in accord with the expected structures. Thermotropic behavior of the teraryl
      compounds was investigated using polarised optical microscopy and differential
      scanning calorimetry. All compounds exhibited both enantiotropic nematic and
      smectic A phases, with an additional enantiotropic smectic C phase when n = 7 and
      8. Polymesomorphism appears to be a common behavior in this series of linear
      liquid crystal compounds.

PMID- 24036441
TI  - Long non-coding RNAs and complex human diseases.
AB  - Long non-coding RNAs (lncRNAs) are a heterogeneous class of RNAs that are
      generally defined as non-protein-coding transcripts longer than 200 nucleotides.
      Recently, an increasing number of studies have shown that lncRNAs can be involved
      in various critical biological processes, such as chromatin remodeling, gene
      transcription, and protein transport and trafficking. Moreover, lncRNAs are
      dysregulated in a number of complex human diseases, including coronary artery
      diseases, autoimmune diseases, neurological disorders, and various cancers, which
      indicates their important roles in these diseases. Here, we reviewed the current
      understanding of lncRNAs, including their definition and subclassification,
      regulatory functions, and potential roles in different types of complex human
      diseases.

PMID- 24036440
TI  - Peptide-lipid interactions: experiments and applications.
AB  - The interactions between peptides and lipids are of fundamental importance in the
      functioning of numerous membrane-mediated cellular processes including
      antimicrobial peptide action, hormone-receptor interactions, drug bioavailability
      across the blood-brain barrier and viral fusion processes. Moreover, a major goal
      of modern biotechnology is obtaining new potent pharmaceutical agents whose
      biological action is dependent on the binding of peptides to lipid-bilayers.
      Several issues need to be addressed such as secondary structure, orientation,
      oligomerization and localization inside the membrane. At the same time, the
      structural effects which the peptides cause on the lipid bilayer are important
      for the interactions and need to be elucidated. The structural characterization
      of membrane active peptides in membranes is a harsh experimental challenge. It is
      in fact accepted that no single experimental technique can give a complete
      structural picture of the interaction, but rather a combination of different
      techniques is necessary.

PMID- 24036444
TI  - A facile and efficient synthesis of diaryl amines or ethers under microwave
      irradiation at presence of KF/Al2O3 without solvent and their anti-fungal
      biological activities against six phytopathogens.
AB  - A series of diaryl amines, ethers and thioethers were synthesized under microwave
      irradiation efficiently at presence of KF/Al2O3 in 83%-96% yields without any
      solvent. The salient characters of this method lie in short reaction time, high
      yields, general applicability to substrates and simple workup procedure. At the
      same time, their antifungal biological activities against six phytopathogen were
      evaluated. Most of the compounds (3b, 3c, 3g-o) are more potent than thiophannate
      methyl against to Magnaporthe oryzae. This implies that diaryl amine or ether
      moiety may be helpful in finding a fungicide against Magnaporthe oryzae.

PMID- 24036443
TI  - ARID1A mutations and PI3K/AKT pathway alterations in endometriosis and
      endometriosis-associated ovarian carcinomas.
AB  - Endometriosis is a common gynecological disease affecting 6%-10% of women of
      reproductive age and is characterized by the presence of endometrial-like tissue
      in localizations outside of the uterine cavity as, e.g., endometriotic ovarian
      cysts. Mainly, two epithelial ovarian carcinoma subtypes, the ovarian clear cell
      carcinomas (OCCC) and the endometrioid ovarian carcinomas (EnOC), have been
      molecularly and epidemiologically linked to endometriosis. Mutations in the gene
      encoding the AT-rich interacting domain containing protein 1A (ARID1A) have been
      found to occur in high frequency in OCCC and EnOC. The majority of these
      mutations lead to a loss of expression of the ARID1A protein, which is a subunit
      of the SWI/SNF chromatin remodeling complex and considered as a bona fide tumor
      suppressor. ARID1A mutations frequently co-occur with mutations, leading to an
      activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, such as
      mutations in PIK3CA encoding the catalytic subunit, p110alpha, of PI3K. In
      combination with recent functional observations, these findings strongly suggest
      cooperating mechanisms between the two pathways. The occurrence of ARID1A
      mutations and alterations in the PI3K/AKT pathway in endometriosis and
      endometriosis-associated ovarian carcinomas, as well as the possible functional
      and clinical implications are discussed in this review.

PMID- 24036446
TI  - Conformational change of a unique sequence in a fungal galectin from Agrocybe
      cylindracea controls glycan ligand-binding specificity.
AB  - A fungal galectin from Agrocybe cylindracea (ACG) exhibits broad binding
      specificity for beta-galactose-containing glycans. We determined the crystal
      structures of wild-type ACG and the N46A mutant, with and without glycan ligands.
      From these structures and a saccharide-binding analysis of the N46A mutant, we
      revealed that a conformational change of a unique insertion sequence containing
      Asn46 provides two binding modes for ACG, and thereby confers broad binding
      specificity. We propose that the unique sequence provides these two distinct
      glycan-binding modes by an induced-fit mechanism.

PMID- 24036445
TI  - Nuclear-encoded chloroplast RNA polymerase sigma factor SIG2 activates
      chloroplast-encoded phycobilisome genes in a red alga, Cyanidioschyzon merolae.
AB  - The phycobilisome (PBS) is a photosynthetic light-harvesting complex in red
      algae, whose structural genes are separately encoded by both the nuclear and
      chloroplast genomes. While the expression of PBS genes in both genomes is
      responsive to environmental changes to modulate light-harvesting efficiency,
      little is known about how gene expression of the two genomes is coordinated. In
      this study, we focused on the four nuclear-encoded chloroplast sigma factors to
      understand aspects of this coordination, and found that SIG2 directs the
      expression of chloroplast PBS genes in the red alga Cyanidioschyzon merolae. 

PMID- 24036447
TI  - Structural differences between the closed and open states of channelrhodopsin-2
      as observed by EPR spectroscopy.
AB  - Channelrhodopsin is a cation channel with the unique property of being activated
      by light. To address structural changes of the open state of the channel, two
      variants, which contain either 1 or 2 wild-type cysteines, were derivatised with
      nitroxide spin label and subjected to electron paramagnetic resonance
      spectroscopy. Both variants contained the C128T mutation to trap the long-lived
      P3(520) state by illumination. Comparison of spin-spin distances in the dark
      state and after illumination reflect conformational changes in the conductive
      P3(520) state involving helices B and F. Spin distance measurements reveal that
      channelrhodopsin forms a dimer even in the absence of intermolecular N-terminal
      cysteines. 

PMID- 24036448
TI  - Mitochondrial G protein coupled receptor kinase 2 regulates proinflammatory
      responses in macrophages.
AB  - G-protein-coupled receptor kinase 2 (GRK2) levels are elevated in inflammation
      but its role is not clear yet. Here we show that GRK2 expression is dependent on
      NFkappaB transcriptional activity. In macrophages, LPS induces GRK2 accumulation
      in mitochondria increasing biogenesis. The overexpression of the carboxy-terminal
      domain of GRK2 (betaARK-ct), known to displace GRK2 from plasma membranes,
      induces earlier localization of GRK2 to mitochondria in response to LPS leading
      to increased mt-DNA transcription and reduced ROS production and cytokine
      expression. Our study shows the relevance of GRK2 subcellular localization in
      macrophage biology and its potential therapeutic properties in inflammation. 

PMID- 24036449
TI  - Hepatitis B virus core protein interacts with CD59 to promote complement-mediated
      liver inflammation during chronic hepatitis B virus infection.
AB  - The inflammatory response mediated by the immune system is the major cause of
      hepatitis B virus (HBV)-associated liver injury. Here, we identified CD59, as a
      novel HBc-interacting protein in hepatocytes by tandem affinity purification
      (TAP) screening. The expression of CD59 was markedly down-regulated in HBc
      transfected HepG2 or HepG2.215 cells, which resulted in an upshift of hepatocyte
      sensitivity to membrane attack complex (MAC)-induced cell lysis. These results
      were consistent with the accumulation of MACs in the liver of HBV-infected
      patients. Additional analyses using laser confocal microscopy, quantitative PCR
      and flow cytometry revealed that CD59 was specifically translocated to the
      nucleus upon binding to HBc, which induced the down-regulation of CD59 on both
      the mRNA and protein levels. 

PMID- 24036451
TI  - PIH1D1 interacts with mTOR complex 1 and enhances ribosome RNA transcription.
AB  - PIH1D1 is the defining component of the R2TP complex. Recently, R2TP has been
      reported to stabilize mTOR (mammalian target of rapamycin), an important
      regulator of cell growth and protein synthesis. Two complexes of mTOR, mTORC1 and
      mTORC2, have been identified. We demonstrate that immunoprecipitation (IP) of
      PIH1D1 results in the co-IP of Raptor (mTORC1 specific), but not Rictor (mTORC2
      specific), and that knockdown of PIH1D1 decreases mTORC1 assembly, S6 kinase
      phosphorylation (indicator of mTORC1 activity), and rRNA transcription without
      affecting mTORC2 in human breast cancer MCF-7 cells. In addition, we provide
      evidence that PIH1D1 is overexpressed in various breast cancer cell lines. These
      findings collectively suggest that PIH1D1 may have an important role in mTORC1
      regulation in breast cancers. 

PMID- 24036452
TI  - A regulatory domain controls the transport activity of a twin-arginine signal
      peptide.
AB  - The twin-arginine translocation (Tat) pathway is used by bacteria for the
      transmembrane transport of folded proteins. Proteins are targeted to the Tat
      translocase by signal peptides that have common tripartite structures consisting
      of polar n-regions, hydrophobic h-regions, and polar c-regions. In this work, the
      signal peptide of [NiFe] hydrogenase-1 from Escherichia coli has been studied.
      The hydrogenase-1 signal peptide contains an extended n-region that has a
      conserved primary structure. Genetic and biochemical approaches reveal that the
      signal peptide n-region is essential for hydrogenase assembly and acts as a
      regulatory domain controlling transport activity of the signal peptide. 

PMID- 24036450
TI  - Solution NMR determination of hydrogen bonding and base pairing between the glyQS
      T box riboswitch Specifier domain and the anticodon loop of tRNA(Gly).
AB  - In Gram-positive bacteria the tRNA-dependent T box riboswitch regulates the
      expression of many amino acid biosynthetic and aminoacyl-tRNA synthetase genes
      through a transcription attenuation mechanism. The Specifier domain of the T box
      riboswitch contains the Specifier sequence that is complementary to the tRNA
      anticodon and is flanked by a highly conserved purine nucleotide that could
      result in a fourth base pair involving the invariant U33 of tRNA. We show that
      the interaction between the T box Specifier domain and tRNA consists of three
      Watson-Crick base pairs and that U33 confers stability to the complex through
      intramolecular hydrogen bonding. Enhanced packing within the Specifier domain
      loop E motif may stabilize the complex and contribute to cognate tRNA selection. 

PMID- 24036453
TI  - Analysis of productive binding modes in the human chitotriosidase.
AB  - Human chitotriosidase (HCHT) is a family 18 chitinase that is an innate part of
      the immune system. We have mapped preferred productive binding modes of chito
      oligosaccharide substrates to HCHT and the data show that HCHT has strong binding
      affinity in the +3 subsite. Moreover, HCHT shows anomer-specific binding
      affinities in subsites +2 and +3. These features could endorse HCHT with higher
      endo-activity and a higher transglycosylation potential. 

PMID- 24036455
TI  - The role of mRNA-based duplication in the evolution of the primate genome.
AB  - Analysis of the human genome suggests novel genes created by retroposition may
      play an important role in primate evolution. However, data from non-human
      primates is still scarce. A comprehensive comparison was thus performed among
      four primate genomes (human, chimpanzee, orangutan, and macaque), which detects
      elevated rates of retroposition in both the common ancestor of hominoids and
      macaques. Further analysis shows approximately 10% of intact retrocopies may be
      under positive selection and at least 4% of retrocopies become functional copies
      eventually. Moreover, human intact retrocopies were found enriched in
      transcription-related functions. Collectively, these findings emphasize the
      important contribution of retroposition to primate genome evolution. 

PMID- 24036454
TI  - Functional conservation between mammalian MGRN1 and plant LOG2 ubiquitin ligases.
AB  - Plant LOSS OF GDU 2 (LOG2) and Mammalian Mahogunin Ring Finger 1 (MGRN1) proteins
      are RING-type E3 ligases sharing similarity N-terminal to the RING domain.
      Deletion of this region disrupts the interaction of LOG2 with the plant membrane
      protein GLUTAMINE DUMPER1 (GDU1). Phylogenetic analysis identified two clades of
      LOG2/MGRN1-like proteins in vertebrates and plants. The ability of MGRN1 to
      functionally replace LOG2 was tested. MGRN1 ubiquitylates GDU1 in vitro and can
      partially substitute for LOG2 in the plant, partially restoring amino acid
      resistance to a GDU1-myc over-expression, log2-2 background. Altogether, these
      results suggest a conserved function for the N-terminal domain in evolution. 

PMID- 24036456
TI  - ONTD induces apoptosis of human hepatoma Bel-7402 cells via a MAPK-dependent
      mitochondrial pathway and the depletion of intracellular glutathione.
AB  - 3-Oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile (ONTD) is a novel
      synthetic derivative of glycyrrhetinic acid (GA), which has the ability to
      inhibit the proliferation of human hepatocellular carcinoma (HCC) cells. However,
      the mechanisms by which ONTD exerts its inhibitory effects remain elusive. The
      present study was conducted to investigate the cytotoxicity of ONTD in Bel-7402
      cells and its molecular mechanisms. We found that ONTD depleted intracellular
      GSH, increased the level of ROS, and consequently induced mitochondrial
      permeability transition (MPT) leading to the release of apoptosis-inducing factor
      (AIF) and cytochrome c (Cyt c) to the cytosol. Mitochondrial alteration and
      subsequent apoptotic cell death in ONTD-treated Bel-7402 cells could be blocked
      by addition of exogenous antioxidants N-acetylcystein (NAC), GSH and the MTP
      inhibitor cyclosporin A (CsA). In addition, ONTD activated the phosphorylation of
      c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPK)
      but not extracellular signal-regulated protein kinases (ERK 1/2). When the cells
      were exposed to SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), the
      deregulation of the expression of apoptotic proteins was attenuated. Furthermore,
      40 mg/kg ONTD significantly reduced tumor weight (-70.62%, p<0.01) in the H22
      tumor-bearing mouse model in vivo. Taken together, these findings provide the
      first experimental evidence supporting that ONTD could induce apoptosis of Bel
      7402 cells via MAPK-mediated mitochondrial pathway and ONTD has the potential to
      be developed as a therapeutic agent for the treatment of HCC.

PMID- 24036457
TI  - Frequency-specific plasticity of the auditory cortex elicited by thalamic
      stimulation in the rat.
AB  - In a process known as frequency-specific plasticity, electrical stimulation of
      the ventral division of the medial geniculate body (MGBv) in the thalamus evokes
      a shift in the frequency-tuning curves of auditory cortical (AC) neurons toward
      the best frequency (BF) of stimulated MGBv neurons. However, the underlying
      synaptic mechanisms of this process are uncharacterized. To investigate whether
      this dynamic change depends on thalamocortical (TC) synaptic plasticity, we
      studied frequency-specific changes in synaptic transmission efficacy in TC
      pathways evoked by thalamic stimulation. Specifically, we induced cortical
      plasticity by repetitive focal electrical stimulation of the MGBv in rats and
      measured receptive field shifts and local field potentials in AC neurons. Our
      data show that focal electrical stimulation of the MGBv induced receptive field
      shifts as well as long-term potentiation or depression of the local field
      potentials in AC neurons. The evoked potentiation and depression depended on the
      frequency of the electrical stimulation of the MGBv synchronized with the BF of
      MGBv and AC neurons. Receptive field shifts were produced by inhibition of
      responses at the BF of the recorded AC neurons and facilitation of responses at
      the BF of the stimulated MGBv neurons. These results suggest that MGBv neurons
      play a decisive role in the expression of AC synaptic plasticity and that
      activation of different frequency-specific TC pathways may be the synaptic
      mechanism underlying this plasticity. 

PMID- 24036458
TI  - Altered expression of miR-146a in myasthenia gravis.
AB  - The purpose of this study was to analyze the expression of miR-146a in PBMCs
      obtained from patients with myasthenia gravis (MG) and healthy controls and to
      investigate the effect of the inhibition of miR-146a on the activation of AchR
      specific B cells obtained from mice. The expression of miR-146a levels in PBMCs
      obtained from patients with MG and healthy controls were determined by qRT-PCR.
      MiR-146a's complementary fragment, AntagomiR-146a, was synthesized as inhibitor,
      and the nonfunctional fragment, which has similar construction to AntagomiR-146a,
      was synthesized as negative control inhibitor. The expression of miR-146a, CD40,
      CD80 and CD86 on AchR specific B cells were analyzed by qRT-PCR and flow
      cytometry. Western blotting was used to detect the expression of TLR4, NF-kappaB
      and Bcl-2 .The expression of miRNA-146a in PBMCs obtained from patients with MG
      was significantly upregulated compared to healthy controls (P<0.01). Transfection
      with miR-146a inhibitor dramatically decreased expression of miR-146a, CD40,
      CD80, TLR4 and NF-kappaB on AchR specific B cells compared to mock transfected
      cells. We conclude that abnormal expression/regulation of miR-146a may play an
      important role in the regulation of AchR specific B cells and contribute to the
      pathogenesis of MG. 

PMID- 24036459
TI  - Parietal EEG alpha suppression time of memory retrieval reflects memory load
      while the alpha power of memory maintenance is a composite of the visual process
      according to simultaneous and successive Sternberg memory tasks.
AB  - The present study investigated EEG alpha activity during visual Sternberg memory
      tasks using two different stimulus presentation modes to elucidate how the
      presentation mode affected parietal alpha activity. EEGs were recorded from 10
      healthy adults during the Sternberg tasks in which memory items were presented
      simultaneously and successively. EEG power and suppression time (ST) in the alpha
      band (8-13Hz) were computed for the memory maintenance and retrieval phases. The
      alpha activity differed according to the presentation mode during the maintenance
      phase but not during the retrieval phase. Results indicated that parietal alpha
      power recorded during the maintenance phase did not reflect the memory load
      alone. In contrast, ST during the retrieval phase increased with the memory load
      for both presentation modes, indicating a serial memory scanning process,
      regardless of the presentation mode. These results indicate that there was a
      dynamic transition in the memory process from the maintenance phase, which was
      sensitive to external factors, toward the retrieval phase, during which the
      process converged on the sequential scanning process, the Sternberg task
      essentially required. 

PMID- 24036460
TI  - Blockade of B2 receptors attenuates the responses of group III afferents to
      static contraction.
AB  - Recent evidence has been presented demonstrating that group III mechanoreceptors
      comprise an important part of the sensory arm of the exercise pressor reflex,
      which in turn functions to increase arterial blood flow to contracting skeletal
      muscles. Although group III afferents are stimulated by mechanical distortion of
      their receptive fields, they are also stimulated by bradykinin, which is produced
      by skeletal muscle when it contracts. Moreover, blockade of B (bradykinin)2
      receptors has been shown to decrease the magnitude of the exercise pressor
      reflex. Nevertheless, the effect of blockade of B2 receptors on responses of
      group III afferents to contraction is not known. We therefore determined the
      effect of B2 receptor blockade with HOE 140 (40MUg/kg) on the responses to both
      static and intermittent contraction of group III afferents with endings in the
      triceps surae muscle of decerebrated unanesthetized cats. We found that HOE 140
      significantly attenuated (P=0.04) the responses of 14 group III afferents to
      static contraction, but did not significantly attenuate (P=0.16) the responses of
      16 group III afferents to intermittent contraction. The attenuation induced by
      HOE 140 was present throughout the static contraction period, and led us to
      speculate that blockade of B2 receptors on the endings of group III afferents
      decreased their sensitivity to mechanical events occurring in the working
      muscles. 

PMID- 24036461
TI  - Interactive effects of cell therapy and rehabilitation realize the full potential
      of neurogenesis in brain injury model.
AB  - The therapeutic effect of rehabilitation after cell therapy for brain injury
      remains unclear. Here, we report the neural stem/progenitor cells transplantation
      into a brain injury mouse model followed by treadmill exercise training. Among
      all experimental groups, mice that underwent transplantation and treadmill
      exercise demonstrated significant functional motor and electrophysiological
      improvement. Transplanted cells at the brain injury site were observed and
      differentiated into neurons and astrocytes. Transplanted cells significantly
      differentiated into neurons in the mice that underwent transplantation and
      treadmill exercise compared with those treated with only transplantation.
      Furthermore, the expression of brain-derived neurotrophic factor and growth
      associated protein 43 mRNAs were significantly up-regulated in the mice that
      underwent transplantation and treadmill exercise than in those in other
      experimental groups during the early recovery stage. These results suggest that
      rehabilitation after neural stem/progenitor cell transplantation enhances
      neurogenesis and promotes the recovery of motor function in brain injury model
      mice. 

PMID- 24036463
TI  - The role of motivational factors in the relationship between hypnotizability and
      pain-inducing imagery.

PMID- 24036462
TI  - The mitochondrial protective mechanism of olfactory ensheathing cells conditioned
      medium protects against H2O2-induced injury in astrocytes.
AB  - Our previous studies showed that olfactory ensheathing cells conditioned medium
      (OECCM), has a positive effect against apoptosis in ASTs and prevents the
      morphology changes in the, mitochondria, but the accurate mechanism is still
      unknown. In this study, we examined the mitochondrial mechanism of OECCM which
      may protect against H2O2-induced injury in ASTs. It was, found that OECCM could
      protect ASTs from the injury of 500MUmol/L H2O2, decrease the intracellular, ROS
      and Ca(2+) level, as well inhibit apoptosis and the expression of cleaved caspase
      3. Further, investigations showed that OECCM could increase both the
      mitochondrial membrane potential and the, ATP level, as well enhance the cell
      respiratory function. In summary, OECCM could protect ASTs from, damages induced
      by H2O2. Its mechanism may be related to the decrease of ROS generation and the,
      overloading of Ca(2+), then stabilization of the mitochondrial function. 

PMID- 24036464
TI  - Ndfip1 expression in developing neurons indicates a role for protein
      ubiquitination by Nedd4 E3 ligases during cortical development.
AB  - During development, protein substrates need to be removed and degraded when they
      are no longer required. The E3 ubiquitin ligases, including Nedd4 family
      proteins, are a major group of enzymes responsible for adding ubiquitin chains to
      protein substrates prior to their degradation. Ndfip1 (Nedd4 family-interacting
      protein 1) is an adaptor and activator for Nedd4-family ubiquitin ligases for
      increasing substrate specificity. To study Nedd4-mediated ubiquitination during
      cortical development, we have mapped the spatio-temporal dynamics of Ndfip1
      protein expression by immunocytochemistry. Ndfip1 expression was observed from
      embryonic day 11 (E11.5) until adult stages. Its presence increased during the
      postnatal stages and peaked at postnatal day 7 (P7). Spatially, Ndfip1 was found
      in the ventricular and marginal zones during corticogenesis but also in the
      cortical plate and subplate during midstage cortical development (E15.5).
      Postnatally, Ndfip1 was expressed in all cortical neurons (but not in glial
      cells) and this expression was both ubiquitous and uniform across cortical layers
      involving both pyramidal and non-pyramidal neurons. This consistent but dynamic
      pattern of Ndfip1 expression in temporal and spatial domains of the cortical
      landscape is indicative of complex programs of protein ubiquitination during
      corticogenesis. 

PMID- 24036465
TI  - The effect of injection of EGb 761 into the lateral ventricle on hippocampal cell
      apoptosis and stem cell stimulation in situ of the ischemic/reperfusion rat
      model.
AB  - EGb 761 is main active ingredient of the popular and standardized natural extract
      Ginkgo biloba, which is known to benefit ischemic stroke. In this study we
      investigated the potential neuroprotective effect of EGb 761 on the hippocampus
      in the ischemic/reperfusion rat model. Significant recovery of motor function was
      seen in EGb 761 treated group compared to vehicle treated group. Infarct volume,
      as revealed by 1% 2,3,5-triphenyltetrazolium chloride (TTC) staining, was
      significantly reduced, coupled with conspicuous suppression of neurons apoptosis
      and significant increments in the cell proliferation and migration in
      hippocampus. This study reports the therapeutic potential of EGb 761 in stroke
      animals, which could be related to the attenuation of apoptosis and enhancement
      of neurogenesis. 

PMID- 24036466
TI  - Anodal tDCS increases corticospinal output and projection strength in multiple
      sclerosis.
AB  - The application of anodal transcranial direct current stimulation (atDCS) to the
      human brain has been shown to elicit corticospinal (CS) excitability changes.
      This study evaluated the effect of a single session of atDCS on CS excitability
      in patients with multiple sclerosis (MS). atDCS and sham tDCS (stDCS) were
      applied to the primary motor cortex (M1) contralateral to the more severely
      impaired hand for 20min in a double-blinded crossover design. Changes in CS
      excitability were assessed using transcranial magnetic stimulation (TMS). The
      area under the recruitment curves increased significantly after application of
      atDCS (+56.58%, p=0.023) but not after stDCS. A sigmoidal curve-analysis revealed
      a higher plateau of the curve after atDCS (+22.2%, p<0.001). Our results showed
      that atDCS over M1 has the ability to increase CS output and projection strength
      in MS-patients, suggesting that atDCS can be considered during neural
      rehabilitation to facilitate motor recovery in MS. 

PMID- 24036467
TI  - Age-associated miRNA alterations in skeletal muscle from rhesus monkeys reversed
      by caloric restriction.
AB  - The levels of microRNAs (miRNAs) are altered under different conditions such as
      cancer, senescence, and aging. Here, we have identified differentially expressed
      miRNAs in skeletal muscle from young and old rhesus monkeys using RNA sequencing.
      In old muscle, several miRNAs were upregulated, including miR-451, miR-144, miR
      18a and miR-15a, while a few miRNAs were downregulated, including miR-181a and
      miR-181b. A number of novel miRNAs were also identified, particularly in old
      muscle. We also examined the impact of caloric restriction (CR) on miRNA
      abundance by reverse transcription (RT) followed by real-time, quantitative
      (q)PCR analysis and found that CR rescued the levels of miR-181b and
      chr1:205580546, and also dampened the age-induced increase in miR-451 and miR-144
      levels. Our results reveal that there are changes in expression of known and
      novel miRNAs with skeletal muscle aging and that CR may reverse some of these
      changes to a younger phenotype. 

PMID- 24036468
TI  - A disorder-to-order structural transition in the COOH-tail of Fz4 determines
      misfolding of the L501fsX533-Fz4 mutant.
AB  - Frizzled 4 belongs to the superfamily of G protein coupled receptors. The
      unstructured cytosolic tail of the receptor is essential for its activity. The
      mutation L501fsX533 in the fz4 gene results in a new COOH-tail of the receptor
      and causes a form of Familial exudative vitreoretinopathy. Here we show that the
      mutated tail is structured. Two amphipathic helices, displaying affinity for
      membranes and resembling the structure of Influenza Hemagglutinin fusion peptide,
      constitute the new fold. This tail induces the aggregation of the receptor in the
      Endoplasmic Reticulum and it is sufficient to block the export to the Golgi of a
      chimeric VSVG protein containing the mutated tail. Affecting the tail's
      structure, net charge or amphipathicity relocates the mutated Fz4 receptor to the
      Plasma Membrane. Such disorder-to-order structural transition was never described
      in GPCRs and opens a new scenario on the possible effect of mutations on
      unstructured regions of proteins. 

PMID- 24036469
TI  - Moving difference (MDIFF) non-adiabatic rapid sweep (NARS) EPR of copper(II).
AB  - Non-adiabatic rapid sweep (NARS) EPR spectroscopy has been introduced for
      application to nitroxide-labeled biological samples (Kittell et al., 2011).
      Displays are pure absorption, and are built up by acquiring data in spectral
      segments that are concatenated. In this paper we extend the method to frozen
      solutions of copper-imidazole, a square planar copper complex with four in-plane
      nitrogen ligands. Pure absorption spectra are created from concatenation of 170 5
      gauss segments spanning 850 G at 1.9 GHz. These spectra, however, are not
      directly useful since nitrogen superhyperfine couplings are barely visible.
      Application of the moving difference (MDIFF) algorithm to the digitized NARS pure
      absorption spectrum is used to produce spectra that are analogous to the first
      harmonic EPR. The signal intensity is about four times higher than when using
      conventional 100 kHz field modulation, depending on line shape. MDIFF not only
      filters the spectrum, but also the noise, resulting in further improvement of the
      SNR for the same signal acquisition time. The MDIFF amplitude can be optimized
      retrospectively, different spectral regions can be examined at different
      amplitudes, and an amplitude can be used that is substantially greater than the
      upper limit of the field modulation amplitude of a conventional EPR spectrometer,
      which improves the signal-to-noise ratio of broad lines.

PMID- 24036470
TI  - Formulation and utilization of choline based samples for dissolution dynamic
      nuclear polarization.
AB  - Hyperpolarization by the dissolution dynamic nuclear polarization (DNP) technique
      permits the generation of high spin polarization of solution state. However,
      sample formulation for dissolution-DNP is often difficult, as concentration and
      viscosity must be optimized to yield a dissolved sample with sufficient
      concentration, while maintaining polarization during the dissolution process. The
      unique chemical properties of choline permit the generation of highly soluble
      salts as well as deep eutectic mixtures with carboxylic acids and urea. We
      describe the formulation of these samples and compare their performance to more
      traditional sample formulations. Choline yields stable samples with exceptional
      polarization performance while simultaneously offering the capability to easily
      remove the choline after dissolution, perform experiments with the hyperpolarized
      choline, or anything in between. 

PMID- 24036471
TI  - Gallic acid prevents memory deficits and oxidative stress induced by
      intracerebroventricular injection of streptozotocin in rats.
AB  - In the present study, we evaluated the effects of gallic acid (GA; 30 mg/kg,
      orally, once daily for 26 days starting from day 5 prior to streptozotocin
      injection) on cognitive impairment and cerebral oxidative stress induced by
      intracerebroventricular-streptozotocin (ICV-STZ; bilaterally, two doses of 3
      mg/kg) injection as an animal model of sporadic Alzheimers type (SDAT) in rats.
      The results showed that ICV-STZ-injection reduced the passive avoidance and
      spatial memory performance associated with decreased non-enzymatic [total thiol
      concentration, -58.5%, -50.7%] and enzymatic [superoxide dismutase (SOD, -30.2%, 
      32.9%), catalase (CAT, -43.5%, -50.7%), glutathione peroxidase (GPx, -57.1%, 
      61.7%)] activities and increased the level of thio-barbituric acid reactive
      species (TBARS, +103.5%, +82.5%) in the hippocampus and cerebral cortex,
      respectively. In contrast, chronic administration of GA significantly prevented
      cognitive deficits and biochemical alterations in the ICV-STZ rats. These
      findings highlight the beneficial role of GA in the ICV-STZ rats via enhancement
      of cerebral antioxidant defense system. Thus, it may have a therapeutic value for
      the treatment of SDAT.

PMID- 24036472
TI  - Combined prenatal and postnatal butyl paraben exposure produces autism-like
      symptoms in offspring: comparison with valproic acid autistic model.
AB  - The aim of this work is to evaluate the impact of butyl paraben (BP) in brain of
      the pups developed for mothers administered BP from early pregnancy till weaning
      and its effect on studying the behavior, brain neurotransmitters and brain
      derived neurotrophic factor BDNF via comparing the results with valproic acid
      (VA) autistic-rat model preparing by a single oral injection dose of VA (800
      mg/kg b.wt) at the 12.5 days of gestation. Butyl paraben was orally and
      subcutaneously administered (200 mg/kg b.wt) to pregnant rats from gestation day
      1 to lactation day 21. The offspring male rats were subjected at the last 3 days
      of lactation to Morris water maze and three chamber sociability test then
      decapitated and the brain was excised and dissected to the cortex, hippocampus,
      cerebellum, midbrain and pons for the determination of norepinephrine, dopamine
      and serotonin (NE, DA and 5-HT) and cortex amino acids and whole brain BDNF. The
      results showed similar social and learning and memory behavioral deficits in VA
      rat model and the butyl paraben offspring in comparison with the controls. Also,
      some similar alterations were observed in monoamine content, amino acids and BDNF
      factor in the autistic-like model and butyl paraben offspring in comparison with
      the controls. The alterations were recorded notably in hippocampus and pons NE,
      midbrain DA, hippocampus and midbrain 5-HT, and frontal cortex GABA and
      asparagine. These data suggest that prenatal exposure to butyl paraben induced
      neuro-developmental disorders similar to some of the neurodevelopmental disorders
      observed in the VA model of autism.

PMID- 24036473
TI  - Anxiolytic-like effects of carvacryl acetate, a derivative of carvacrol, in mice.
AB  - Studies showing anxiolytic-like properties of natural products have grown. This
      paper evaluated if carvacryl acetate (CA) could be studied as an alternative drug
      to treat anxiety disorders. Elevated plus maze (EPM) tests , light-dark box (LDB)
      tests, and marble-burying tests (MBTs) were performed on mice. In the first
      protocol, the anxiolytic-like activities of CA 25, 50, 75 and 100mg/kg at single
      doses were compared to those of the vehicle, buspirone 5mg/kg (BUSP) and diazepam
      1mg/kg (DZP). In the second protocol, the anxiolytic-like actions of CA were
      tested for GABAergic and serotonergic systems. The time spent in the open arms
      (TSOA) and the number of open arms entries (NOAE) were measured in EPM; the time
      spent in the light box (TSLB) and the number of entries to light box (NELB) were
      measured in LDB; and the number of marbles buried (NMB) were measured in MBT. CA
      increased TSOA and NOAE in the EPM, as well as TSLB and NELB in the LDB and the
      NMB in the MBT. The anxiolytic-like activity of CA 25; 50; 75 and 100mg/kg was
      not associated with psychomotor retardation in the open field test and in the
      Rota rod test, contrarily with what happened with DZP. In the second protocol, to
      suggest the mechanism of action of CA, flumazenil 25mg/kg ip (FLU) and WAY
      100,635 10mg/kg ip (WAY-5-HT1A antagonist) were also used. FLU+CA100 reduced TSOA
      in the EPM when compared to CA100 but WAY+CA100 did not. In LDB, FLU+CA100
      reduced the TSLB when compared to CA100 but WAY+CA100 did not. In the MBT,
      FLU+CA100 inhibited the effect of CA100 on the NMB but WAY+CA100 did not. In
      conclusion, CA seems to have an anxiolytic-like effect, probably due to GABAergic
      agonist action, without psychomotor side effects. 

PMID- 24036474
TI  - Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system:
      characterization, stability assessment and cytotoxicity.
AB  - Cancer nanotherapeutics is beginning to overwhelm the global research and viewed
      to be the revolutionary treatment regime in the medical field. This investigation
      describes the development of a stable nanostructured lipid carrier (NLC) system
      as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg
      of TAM showed a spherical particle with the size of 46.6nm, polydispersity index
      of 0.267, entrapment efficiency of 99.74% and with the zeta potential of 
      23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7)
      and mice (4T1) mammary breast cancer cell lines were observed. Incubating the
      formulation at the physiological pH resulted into reduced Ostwald ripening rate
      but without any significant change in the absorptivity. When coupled with the
      measurements of zeta potential and Ostwald ripening rate, the absorbance assay
      may be used to predict the long-term stability of drug-loaded nanoparticle
      formulations. The results of the study also suggest that TAM-NLC is a promising
      drug delivery system for breast cancer therapy. This is the first encouraging
      report on the in vitro effect of TAM-NLC against human and mouse mammary
      adenocarcinoma cell lines. 

PMID- 24036475
TI  - Evaluation of clay/poly (L-lactide) microcomposites as anticancer drug, 6
      mercaptopurine reservoir through in vitro cytotoxicity, oxidative stress markers
      and in vivo pharmacokinetics.
AB  - Intercalation of 6-mercaptopurine (6-MP), an antineoplastic drug in interlayer
      gallery of Na(+)-clay (MMT) was further entrapped in poly (L-lactide) matrix to
      form microcomposite spheres (MPs) in order to reduce the cell toxicity and
      enhance in vitro release and pharmacokinetic proficiency. The drug-clay hybrid
      was fabricated via intercalation by ion-exchange method to form MPs from hybrid.
      In vitro drug release showed controlled pattern, fitted to kinetic models
      suggested controlled exchange and partial diffusion through swollen matrix of
      clay inter layered gallery. The in vitro efficacy of formulated composites drug
      was tested in Human neuroblastoma cell line (IMR32) by various cell cytotoxic and
      oxidative stress marker indices. In vivo pharmacokinetics suggested that the
      intensity of formulated drug level in plasma was within remedial borders as
      compared to free drug. These clay based composites therefore have great potential
      of becoming a new dosage form of 6-MP.

PMID- 24036476
TI  - Cardiolipin externalization to the outer mitochondrial membrane acts as an
      elimination signal for mitophagy in neuronal cells.
AB  - Recognition of injured mitochondria for degradation by macroautophagy is
      essential for cellular health, but the mechanisms remain poorly understood.
      Cardiolipin is an inner mitochondrial membrane phospholipid. We found that
      rotenone, staurosporine, 6-hydroxydopamine and other pro-mitophagy stimuli caused
      externalization of cardiolipin to the mitochondrial surface in primary cortical
      neurons and SH-SY5Y cells. RNAi knockdown of cardiolipin synthase or of
      phospholipid scramblase-3, which transports cardiolipin to the outer
      mitochondrial membrane, decreased the delivery of mitochondria to autophagosomes.
      Furthermore, we found that the autophagy protein microtubule-associated-protein-1
      light chain 3 (LC3), which mediates both autophagosome formation and cargo
      recognition, contains cardiolipin-binding sites important for the engulfment of
      mitochondria by the autophagic system. Mutation of LC3 residues predicted as
      cardiolipin-interaction sites by computational modelling inhibited its
      participation in mitophagy. These data indicate that redistribution of
      cardiolipin serves as an 'eat-me' signal for the elimination of damaged
      mitochondria from neuronal cells. 

PMID- 24036478
TI  - Differential and reproductive stage-dependent regulation of vasotocin secretion
      by catecholamines in the catfish Heteropneustes fossilis.
AB  - Vasotocin (VT) is the basic nonapeptide hormone secreted by the neurohypophysis
      of non-mammalian vertebrates and is involved in the regulation of osmoregulation,
      metabolism, cardiovascular function, reproduction and behaviour. Among the
      reproductive function, VT is specifically implicated in final oocyte maturation,
      ovulation, oviposition/parturition in teleosts, amphibians, reptiles, and birds.
      The central catecholaminergic system is involved in the regulation of pituitary
      hormone secretion including gonadotropin, and mediates also changes in
      environmental photoperiod and temperature. The close apposition of the VT and
      catecholaminergic systems in the preoptic area of the hypothalamus signifies a
      strong possibility of their functional interaction. The aim of the present study
      was to investigate the effects of exogenously administered catecholamines on VT
      secretion in two different reproductive phases of female catfish Heteropneustes
      fossilis. For this, the catecholamine precursor L-dihydroxyphenylalanine (L-DOPA)
      and catecholamines (dopamine-DA, norepinephrine-NE, and epinephrine-E) were
      intraperitoneally injected in normal catfish and/or along with alpha
      methylparatyrosine (alpha-MPT, a tyrosine hydroxylase inhibitor). Brain and
      plasma VT levels were measured by specific ELISA, 24h post injection. Both L-DOPA
      and DA inhibited brain and plasma VT levels in a concentration-dependent manner
      in preparatory and prespawning phases. In contrast, NE elicited dose-dependent
      effects: the lowest dose (0.5 ng/g body mass, BM) was ineffective, the median
      dose (1 ng/g BM) stimulated, and the high doses (10 and 100 ng/g BM) inhibited VT
      levels. E stimulated VT levels dose-dependently. A single injection of alpha-MPT
      (250 MUg/g BM) strongly inhibited VT when given alone and enhanced the inhibitory
      effects of L-DOPA and DA in the combination groups. The alpha-MPT inhibition of
      VT was significantly reduced by the injection of NE (5 ng/g BM) and was restored
      or elevated by E. When the adrenergic neurotransmitters were given together with
      alpha-MPT, the inhibitory effect of the latter was abolished and VT levels were
      significantly elevated. Thus, the present data indicate that the physiological
      changes in VT is differentially regulated by the catecholamines (DA inhibits and
      NE/E stimulates VT).

PMID- 24036477
TI  - Spatial sequestration of misfolded proteins by a dynamic chaperone pathway
      enhances cellular fitness during stress.
AB  - The extensive links between proteotoxic stress, protein aggregation and
      pathologies ranging from ageing to neurodegeneration underscore the importance of
      understanding how cells manage protein misfolding. Using live-cell imaging, we
      determine the fate of stress-induced misfolded proteins from their initial
      appearance until their elimination. Upon denaturation, misfolded proteins are
      sequestered from the bulk cytoplasm into dynamic endoplasmic reticulum (ER)
      associated puncta that move and coalesce into larger structures in an energy
      dependent but cytoskeleton-independent manner. These puncta, which we name Q
      bodies, concentrate different misfolded and stress-denatured proteins en route to
      degradation, but do not contain amyloid aggregates, which localize instead to the
      insoluble protein deposit compartment. Q-body formation and clearance depends on
      an intact cortical ER and a complex chaperone network that is affected by
      rapamycin and impaired during chronological ageing. Importantly, Q-body formation
      enhances cellular fitness during stress. We conclude that spatial sequestration
      of misfolded proteins in Q-bodies is an early quality control strategy occurring
      synchronously with degradation to clear the cytoplasm of potentially toxic
      species. 

PMID- 24036479
TI  - The effect of syndecan-4 and glypican-1 expression on age-related changes in
      myogenic satellite cell proliferation, differentiation, and fibroblast growth
      factor 2 responsiveness.
AB  - Satellite cells are multipotential stem cells responsible for muscle growth and
      regeneration. Satellite cell proliferation, differentiation, and responsiveness
      to fibroblast growth factor 2 (FGF2) is, in part, regulated by the heparan
      sulfate proteoglycans syndecan-4 and glypican-1. Syndecan-4 and glypican-1
      expression declines with satellite cell age and may be associated with decreased
      satellite cell activity. The objective of the current study was to determine if
      overexpression of syndecan-4 and glypican-1 would increase proliferation,
      differentiation and FGF2 responsiveness in satellite cells isolated from
      pectoralis major muscle from 16-wk-old turkeys. Overexpression of syndecan-4 and
      glypican-1 did not have a significant effect on proliferation and differentiation
      in 1d, 7 wk, and 16 wk satellite cells, and did not affect FGF2 responsiveness
      during proliferation. Expression of syndecan-4 and glypican-1 increased
      differentiation at 48 h in 1d, 7 wk, and 16 wk cells treated with FGF2.
      Expression of myogenic regulatory factors MyoD, myogenin, and MRF4 was affected
      by the overexpression of syndecan-4 and glypican-1. However, changes in myogenic
      regulatory factor expression did not have a significant effect on proliferation
      or differentiation. These data demonstrate that syndecan-4 and glypican-1 are
      likely not directly associated with the age related decrease in satellite cell
      activity.

PMID- 24036480
TI  - The postpartum management of women with gestational diabetes using a continuum
      model for health care.
AB  - Women with gestational diabetes mellitus require a continuum of care before,
      during, and after pregnancy for optimal management of hyperglycemia. Postpartum
      education and lifestyle modification should begin during pregnancy, and should
      continue during the postpartum period. Women should receive education on the long
      term risk of type 2 diabetes mellitus, and should be encouraged to breastfeed,
      engage in regular physical activity, and select a highly effective contraceptive
      method in preparation for subsequent pregnancy. Postpartum women with gestational
      diabetes mellitus should be empowered to take ownership of their own health,
      including knowledge of health indicators such as weight, waist circumference
      hemoglobin A1C levels, and fasting and postprandial blood glucose levels. 

PMID- 24036481
TI  - Controversies in osteoporosis management: antiresorptive therapy for preventing
      bone loss: when to use one or two antiresorptive agents?
AB  - Women who have significant bone loss or a new fracture on monotherapy are
      considered for combination therapy. Combination therapies increase bone density
      more than monotherapy by targeting different parts of the osteoclast pathway.In
      early postmenopausal women who are symptomatic, the use of combination
      antiresorptives should include hormone therapy with a bisphosphonate or with
      bazodoxifene. In women who initially receive a weaker antiresorptive such as the
      SERM raloxifene, a combination with bisphosphonates and calcium supplementation
      is necessary to prevent bone loss. In older women over 65 years of age who often
      have impaired calcium absorption, the combination of calcitriol with
      bisphosphonates has been shown to increase bone density more than monotherapy. 

PMID- 24036482
TI  - Osteoporosis: what's new and on the horizon.
AB  - In this review, we consider new concepts in the assessment of fracture risk and
      pharmacologic therapy for osteoporosis. We discuss trabecular bone score, a new
      imaging technology that adds information that cannot be obtained by only
      measuring bone mineral density by dual-energy x-ray absorptiometry. We also
      discuss innovations in antiresorptive, osteoanabolic, and combination therapy;
      and newer therapeutic classes, including cathepsin K inhibitors and
      antisclerostin antibodies. We do not cover agents that have not yet been studied
      in human clinical trials or that are no longer under active investigation. 

PMID- 24036483
TI  - Determinants of school activity performance in children with cerebral palsy: a
      multidimensional approach using the ICF-CY as a framework.
AB  - This study aimed to identify the determinants of activity performance in children
      with cerebral palsy (CP) in school by considering factors from the entire scope
      of the International Classification of Functioning, Disability, and Health for
      Child and Youth (ICF-CY). A sample of 167 school-aged children with CP and their
      caregivers were recruited in the study. Activity performance in school settings
      was assessed with part 3 of the School Functional Assessment - Chinese version,
      which divides activity performance into performance of physical activities and
      cognitive/behavioral activities. Possible determinants were collected according
      to all dimensions of the ICF-CY. Multiple regression analyses showed that the
      determinants of performance of physical activities were receiving speech therapy
      in school, diplegia, having a domestic helper, and severity of gross and fine
      motor impairments, explaining 83% of the total variance; the determinants of
      performance of cognitive/behavioral activities were intellectual impairment,
      prosocial behavior, having an assistant in school, educational placement,
      severity of fine motor impairment, accounting for 73% of the total variance.
      Results of the study provide clinicians a holistic understanding of factors
      influencing school activity performance, and enable clinicians to make
      appropriate evaluations and interventions targeted at the determinants to enhance
      children's activity performance in school. 

PMID- 24036484
TI  - Health and wellbeing of Victorian adults with intellectual disability compared to
      the general Victorian population.
AB  - Multiple measures of health and wellbeing of people with intellectual disability
      (ID) and the general Victorian population were compared using representative
      population level data. The sample consisted of adults with ID (N=897) and the
      general Victorian population (N=34,168) living in the state of Victoria in
      Australia. Proxy respondents were interviewed on behalf of people with ID, while
      respondents from the general Victorian population were interviewed directly. The
      data were weighted to reflect the age/sex/geographic distribution of the
      population. Results revealed that adults with ID reported higher prevalence of
      poor social determinants of health, behavioural risk factors, depression,
      diabetes, poor or fair health. A higher proportion of people with ID reported
      blood pressure and blood glucose checks, while a lower proportion reported
      cervical and breast cancer screening, compared with the general Victorian
      population. The survey identified areas where targeted approaches may be
      undertaken to improve the health outcomes of people with ID and provide an
      important understanding of the health and wellbeing of these Victorians. 

PMID- 24036485
TI  - Fine and gross motor skills differ between healthy-weight and obese children.
AB  - Within the obesity literature, focus is put on the link between weight status and
      gross motor skills. However, research on fine motor skills in the obese (OB)
      childhood population is limited. Therefore, the present study focused on possible
      weight related differences in gross as well as fine motor skill tasks. Thirty
      four OB children (12 ? and 22 ?, aged 7-13 years) were recruited prior to
      participating in a multidisciplinary treatment program at the Zeepreventorium (De
      Haan, Belgium). Additionally, a control group of 34 age and gender-matched
      healthy-weight (HW) children was included in the study. Anthropometric measures
      were recorded and gross and fine motor skills were assessed using the Bruininks
      Oseretsky Test of Motor Proficiency, second edition (BOT-2). Results were
      analyzed by independent samples t-tests, multivariate analysis of variance, and a
      chi-squared test. Being OB was detrimental for all subtests evaluating gross
      motor skill performance (i.e., upper-limb coordination, bilateral coordination,
      balance, running speed and agility, and strength). Furthermore, OB children
      performed worse in fine motor precision and a manual dexterity task, when
      compared to their HW peers. No group differences existed for the fine motor
      integration task. Our study provides evidence that lower motor competence in OB
      children is not limited to gross motor skills alone; OB children are also
      affected by fine motor skill problems. Further investigation is warranted to
      provide possible explanations for these differences. It is tentatively suggested
      that OB children experience difficulties with the integration and processing of
      sensory information. Future research is needed to explore whether this assumption
      is correct and what the underlying mechanism(s) could be. 

PMID- 24036487
TI  - Differential impact of tobacco control policies on youth sub-populations.
AB  - BACKGROUND: While previous studies have demonstrated the efficacy of tobacco
      control interventions in reducing tobacco use among youth overall, there have
      been very few studies that examine the potential differential impact of tobacco
      control policies on various youth subgroups, defined by socio-economic status
      (SES), race/ethnicity, and gender. OBJECTIVE: We examined the relationship
      between state-level cigarette prices and smoke-free air laws and youth smoking
      prevalence and intensity for various youth sub-populations in the United States.
      METHODS: We estimated a 2-part model of cigarette demand using data from the 1991
      through 2010 nationally representative surveys of 8th-, 10th-, and 12th-grade
      students as part of the Monitoring the Future project. FINDINGS: We found that
      real cigarette prices are strong determinants of youth smoking. Blacks, females,
      Hispanics, and low-SES subpopulations are found to have a larger price response
      with respect to smoking prevalence than the full sample. Smoke-free air laws are
      found to have a negative effect on smoking prevalence for the full sample and for
      the male, white, and high-SES sub-populations. CONCLUSIONS: This research
      concludes that higher cigarette prices will reduce smoking prevalence rates of
      Blacks, Hispanics, females, and low-SES subpopulations faster than the overall
      youth population and other youth sub-populations. Moreover, this research
      concludes that smoke-free air laws will reduce smoking prevalence for the overall
      youth population with the largest reductions in high SES and male subpopulations.

PMID- 24036488
TI  - Metallo-toeholds: controlling DNA strand displacement driven by Hg(II) ions.
AB  - Toehold-mediated strand displacement is a powerful tool that permits programmable
      control over DNA hybridization. Here, we developed a mechanism for strand
      displacement driven by Hg(2+) ions, in which the insertion of thymine-thymine
      mismatched base pairs on the toeholds provides additional control through
      variation of the concentration of Hg(2+) ions. 

PMID- 24036489
TI  - Fungicides effectively used for growth inhibition of several fungi could induce
      mycotoxin biosynthesis in toxigenic species.
AB  - Seven different commercial fungicides (Aliette, Rovral, Cantus, Ortiva, Luna
      Experience, Fenomenal and Mancozeb) were tested for their ability to inhibit the
      growth of the fungal species Penicillium nordicum, Penicillium verrucosum,
      Verticillium dahliae and Cladosporium sp. In case of the mycotoxigenic strains P.
      nordicum and P. verrucosum, the biosynthesis of the mycotoxins ochratoxin and
      citrinin was determined. Interestingly individual fungicides were only able to
      inhibit the growth of the analyzed fungi to some extent. In case of P. verrucosum
      the fungicide "Rovral", an iprodion belonging to the substance class of
      imidazoles, led to a decrease in the growth rate but to a strong induction of
      mycotoxin biosynthesis as has been described earlier for the strobilurins.
      Consequently before using a given fungicide to protect crops and enhance storage
      life, the applicability of this chemical compound should be tested not only for
      its ability to inhibit fungal growth but also for its effect on level of
      secondary metabolite biosynthesis. 

PMID- 24036490
TI  - Use of peptide thrombopoietin receptor agonist romiplostim (Nplate) in a case of
      primary HIV-associated thrombocytopenia.
AB  - Thrombocytopenia is frequently encountered in HIV-infected patients, and the
      predominant cause is primary HIV-associated thrombocytopenia (PHAT). Standard
      treatment regimens include optimization of antiretroviral therapy, intravenous
      immunoglobulin, anti-D, and corticosteroids. Retreatment due to the inability to
      sustain remission or inferior responses is common, and investigation into the
      safety and efficacy of alternative therapies is warranted. We describe novel and
      effective treatment of PHAT with the peptide thrombopoietin receptor agonist
      romiplostim in a patient with a minimal response to conventional therapy. 

PMID- 24036486
TI  - Strategies to minimize antibiotic resistance.
AB  - Antibiotic resistance can be reduced by using antibiotics prudently based on
      guidelines of antimicrobial stewardship programs (ASPs) and various data such as
      pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics,
      diagnostic testing, antimicrobial susceptibility testing (AST), clinical
      response, and effects on the microbiota, as well as by new antibiotic
      developments. The controlled use of antibiotics in food animals is another
      cornerstone among efforts to reduce antibiotic resistance. All major resistance
      control strategies recommend education for patients, children (e.g., through
      schools and day care), the public, and relevant healthcare professionals (e.g.,
      primary-care physicians, pharmacists, and medical students) regarding unique
      features of bacterial infections and antibiotics, prudent antibiotic prescribing
      as a positive construct, and personal hygiene (e.g., handwashing). The problem of
      antibiotic resistance can be minimized only by concerted efforts of all members
      of society for ensuring the continued efficiency of antibiotics. 

PMID- 24036491
TI  - Bayesian sample size determination for case-control studies when exposure may be
      misclassified.
AB  - Odds ratios are frequently used for estimating the effect of an exposure on the
      probability of disease in case-control studies. In planning such studies, methods
      for sample size determination are required to ensure sufficient accuracy in
      estimating odds ratios once the data are collected. Often, the exposure used in
      epidemiologic studies is not perfectly ascertained. This can arise from recall
      bias, the use of a proxy exposure measurement, uncertain work exposure history,
      and laboratory or other errors. The resulting misclassification can have large
      impacts on the accuracy and precision of estimators, and specialized estimation
      techniques have been developed to adjust for these biases. However, much less
      work has been done to account for the anticipated decrease in the precision of
      estimators at the design stage. Here, we develop methods for sample size
      determination for odds ratios in the presence of exposure misclassification by
      using several interval-based Bayesian criteria. By using a series of prototypical
      examples, we compare sample size requirements after adjustment for
      misclassification with those required when this problem is ignored. We illustrate
      the methods by planning a case-control study of the effect of late introduction
      of peanut to the diet of children to the subsequent development of peanut
      allergy. 

PMID- 24036492
TI  - Increased expression of Drosophila Sir2 extends life span in a dose-dependent
      manner.
AB  - Sir2, a member of the sirtuin family of protein acylases, deacetylates lysine
      residues within many proteins and is associated with lifespan extension in a
      variety of model organisms. Recent studies have questioned the positive effects
      of Sir2 on lifespan inDrosophila. Several studies have shown that increased
      expression of the Drosophila Sir2 homolog (dSir2) extends life span while other
      studies have reported no effect on life span or suggested that increased dSir2
      expression was cytotoxic. To attempt to reconcile the differences in these
      observed effects of dSir2 on Drosophila life span, we hypothesized that a
      critical level of dSir2 may be necessary to mediate life span extension. Using
      approaches that allow us to titrate dSir2 expression, we describe here a strong
      dose-dependent effect of dSir2 on life span. Using the two transgenic dSir2 lines
      that were reported not to extend life span, we are able to show significant life
      span extension when dSir2 expression is induced between 2 and 5-fold. However,
      higher levels decrease life span and can induce cellular toxicity, manifested by
      increased expression of the JNK-signaling molecule Puc phosphatase and induction
      of dnaJ-H. Our results help to resolve the apparently conflicting reports by
      demonstrating that the effects of increased dSir2 expression on life span in
      Drosophila are dependent upon dSir2 dosage. 

PMID- 24036494
TI  - The role of the abnormalities in the distal pathway of cholesterol biosynthesis
      in the Conradi-Hunermann-Happle syndrome.
AB  - Conradi-Hunermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked
      dominant variant of chondrodysplasia punctata (CP) caused by mutations in one
      gene of the distal pathway of cholesterol biosynthesis. It exhibits intense
      phenotypic variation and primarily affects the skin, bones and eyes. The
      ichthyosis following Blaschko's lines, chondrodysplasia punctata and cataracts
      are the typical clinical findings. The cardinal biochemical features are an
      increase in 8(9)-cholestenol and 8-dehydrocholesterol (8DHC), which suggest a
      deficiency in 3beta-hydroxysteroid-Delta8,Delta7-isomerase, also called emopamil
      binding protein (EBP). The EBP gene is located on the short arm of the X
      chromosome (Xp11.22-p11.23) and encodes a 230 amino acid protein with dual
      function. Explaining the clinical phenotype in CDPX2 implies an understanding of
      both the genetics and biochemical features of this disease. CDPX2 displays an X
      linked dominant pattern of inheritance, which is responsible for the distribution
      of lesions in some tissues. The clinical phenotype in CDPX2 results directly from
      impairment in cholesterol biosynthesis, and indirectly from abnormalities in the
      hedgehog signaling protein pathways. This article is part of a Special Issue
      entitled The Important Role of Lipids in the Epidermis and their Role in the
      Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R.
      Feingold and Peter Elias. 

PMID- 24036493
TI  - Fatty aldehyde and fatty alcohol metabolism: review and importance for epidermal
      structure and function.
AB  - Normal fatty aldehyde and alcohol metabolism is essential for epidermal
      differentiation and function. Long-chain aldehydes are produced by catabolism of
      several lipids including fatty alcohols, sphingolipids, ether glycerolipids,
      isoprenoid alcohols and certain aliphatic lipids that undergo alpha- or omega
      oxidation. The fatty aldehyde generated by these pathways is chiefly metabolized
      to fatty acid by fatty aldehyde dehydrogenase (FALDH, alternately known as
      ALDH3A2), which also functions to oxidize fatty alcohols as a component of the
      fatty alcohol:NAD oxidoreductase (FAO) enzyme complex. Genetic deficiency of
      FALDH/FAO in patients with Sjogren-Larsson syndrome (SLS) results in accumulation
      of fatty aldehydes, fatty alcohols and related lipids (ether glycerolipids, wax
      esters) in cultured keratinocytes. These biochemical changes are associated with
      abnormalities in formation of lamellar bodies in the stratum granulosum and
      impaired delivery of their precursor membranes to the stratum corneum (SC). The
      defective extracellular SC membranes are responsible for a leaky epidermal water
      barrier and ichthyosis. Although lamellar bodies appear to be the pathogenic
      target for abnormal fatty aldehyde/alcohol metabolism in SLS, the precise
      biochemical mechanisms are yet to be elucidated. Nevertheless, studies in SLS
      highlight the critical importance of FALDH and normal fatty aldehyde/alcohol
      metabolism for epidermal function. This article is part of a Special Issue
      entitled The Important Role of Lipids in the Epidermis and their Role in the
      Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R.
      Feingold and Peter Elias. 

PMID- 24036495
TI  - Thoracic aortic aneurysm frequency and dissection are associated with fibrillin-1
      fragment concentrations in circulation.
AB  - RATIONALE: Mutations in fibrillin-1 are associated with thoracic aortic aneurysm
      (TAA) in Marfan syndrome. Genome-wide association studies also implicate
      fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is
      characteristic of TAA. OBJECTIVE: Immunoassays were generated to test whether
      circulating fragments of fibrillin-1, or other microfibril fragments, are
      associated with TAA and dissection. METHODS AND RESULTS: Plasma samples were
      obtained from 1265 patients with aortic aneurysm or dissection and from 125
      control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were
      measured with novel immunoassays. One hundred and seventy-four patients (13%) had
      aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and
      1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection
      and 109 (10%) had acute or subacute dissection. Associations of fragment
      concentrations with TAA (versus abdominal aortic aneurysm) or with dissection
      (versus no dissection) were estimated with odds ratios (OR) and 95% confidence
      intervals (CI) adjusted for age, sex, and smoking. Compared with controls,
      significantly higher percentages of aneurysm patients had detectable levels of
      fibrillin fragments. TAA was significantly more common (than abdominal aortic
      aneurysm) in the highest compared with lowest quartile of fibrillin-1
      concentration (OR=2.9; 95% CI, 1.6-5.0). Relative to TAA without dissection,
      acute or subacute dissection (OR=2.9; 95% CI, 1.6-5.3), but not chronic
      dissection, was more frequent in the highest compared with lowest quartile of
      fibrillin-1 concentration. Neither TAA nor dissection was associated with
      fibrillin-2 or fibulin-4. CONCLUSIONS: Circulating fibrillin-1 fragments
      represent a new potential biomarker for TAA and acute aortic dissection.

PMID- 24036497
TI  - Inorganic click (iClick) synthesis of heterotrinuclear Pt(II)/Au(I)2 complexes.
AB  - Metal-azide-metal-acetylide cycloaddition (iClick) reactions to synthesize
      heterotrimetallics and an unexpected novel tetranuclear gold(I) complex, are
      described. In addition, a discussion regarding the connection between traditional
      azide-alkyne cycloaddition reactions and iClick is presented focusing on
      applications towards linking multiple metal ions.

PMID- 24036496
TI  - Liver X receptor activation stimulates iron export in human alternative
      macrophages.
AB  - RATIONALE: In atherosclerotic plaques, iron preferentially accumulates in
      macrophages where it can exert pro-oxidant activities. OBJECTIVE: The objective
      of this study was, first, to better characterize the iron distribution and
      metabolism in macrophage subpopulations in human atherosclerotic plaques and,
      second, to determine whether iron homeostasis is under the control of nuclear
      receptors, such as the liver X receptors (LXRs). METHODS AND RESULTS: Here we
      report that iron depots accumulate in human atherosclerotic plaque areas enriched
      in CD68 and mannose receptor (MR)-positive (CD68(+)MR(+)) alternative M2
      macrophages. In vitro IL-4 polarization of human monocytes into M2 macrophages
      also resulted in a gene expression profile and phenotype favoring iron
      accumulation. However, M2 macrophages on iron exposure acquire a phenotype
      favoring iron release, through a strong increase in ferroportin expression,
      illustrated by a more avid oxidation of extracellular low-density lipoprotein by
      iron-loaded M2 macrophages. In line, in human atherosclerotic plaques,
      CD68(+)MR(+) macrophages accumulate oxidized lipids, which activate LXRalpha and
      LXRbeta, resulting in the induction of ABCA1, ABCG1, and apolipoprotein E
      expression. Moreover, in iron-loaded M2 macrophages, LXR activation induces
      nuclear factor erythroid 2-like 2 expression, thereby increasing ferroportin
      expression, which, together with a decrease of hepcidin mRNA levels, promotes
      iron export. CONCLUSIONS: These data identify a role for M2 macrophages in iron
      handling, a process regulated by LXR activation.

PMID- 24036498
TI  - Reactions of d(0) tungsten alkylidyne complexes with O2 or H2O. Formation of an
      oxo siloxy complex through unusual silyl migrations.
AB  - (Me3SiCH2)3(Me3SiC=)W<-O=PMe3 (1), an adduct between (Me3SiCH2)3W=CSiMe3 (2) and
      O=PMe3, reacts with O2 to give O=W(OSiMe3)(CH2SiMe3)3 (3) and CO2. Reaction of 2
      with H2O yields 3 and the trimer [(MU-O)W(CH2SiMe3)2(=O)(THF)]3 (4). In the
      reaction of D2O with 2, 3-d(n) and methane isotopologues CH2D2, CHD3 and CD4 have
      been observed.

PMID- 24036499
TI  - Simultaneous determination of olmesartan and amlodipine in human plasma and urine
      by ultra performance liquid chromatography tandem mass spectrometry.
AB  - A sensitive and rapid ultra performance liquid chromatography tandem mass
      spectrometry (UPLC-MS/MS) method was developed to determine olmesartan and
      amlodipine levels in human plasma and urine simultaneously. Chromatographic
      separation was carried out on an Acquity UPLC BEH C18 column and mass
      spectrometric analysis was performed using a QTrap5500 mass spectrometer coupled
      with an electro-spray ionization (ESI) source in the positive ion mode. The MRM
      transitions of m/z 447->207 and 409->238 were used to quantify olmesartan and
      amlodipine, respectively. This assay method has been fully validated in terms of
      selectivity, linearity, lower limit of quantification (LLOQ), accuracy,
      precision, stability, matrix effect and recovery. The linearity of this method
      was found to be within the concentration range of 0.2-500ng/mL and 4-5000ng/mL
      for olmesartan in human plasma and urine and 0.1-50ng/mL and 2-1000ng/mL for
      amlodipine in human plasma and urine. Only 2min were needed for an analytical
      run. This assay was used to support a clinical study where multiple oral doses
      were administered to healthy Chinese subjects to investigate the pharmacokinetics
      of olmesartan and amlodipine. 

PMID- 24036500
TI  - Liquid chromatography-tandem mass spectrometry determination of baclofen in
      various biological samples and application to a pharmacokinetic study.
AB  - Baclofen is a structural analogue of gamma-aminobutyric acid (GABA) that has been
      used for the treatment of spasticity since 1977. This study describes a simple
      and sensitive LC/MS/MS assay for the quantification of baclofen in rat plasma,
      urine, as well as various tissue samples. The assay utilized a simple protein
      precipitation and achieved lower limit of quantification (LLOQ) of 0.25ng/mL for
      rat plasma and brain samples and 2ng/mL for rat urine, liver and kidney samples.
      The assay was validated to demonstrate the specificity, linearity, recovery,
      LLOQ, accuracy, precision, and stability by using matrix matched quality control
      samples. There is no endogenous or exogenous peaks interfering with the analytes
      and matrix effects were minimized by optimized separation condition. The assay
      was linear over a concentration range of 0.25-500ng/mL for rat plasma and brain
      tissue, and 2-5000ng/mL for rat urine, kidney and liver with correlation
      coefficients >0.999. The mean intra- and inter-day assay accuracies were 94.6
      104.6 and 96.0-103.6%, respectively. The mean intra- and inter-day precisions
      were 5.71 and 5.70%, respectively. The developed assay was successfully applied
      to a pharmacokinetic study and examined urinary excretion and tissue distribution
      of baclofen in rats following intravenous and oral administration. 

PMID- 24036501
TI  - Forest fire management to avoid unintended consequences: a case study of Portugal
      using system dynamics.
AB  - Forest fires are a serious management challenge in many regions, complicating the
      appropriate allocation to suppression and prevention efforts. Using a System
      Dynamics (SD) model, this paper explores how interactions between physical and
      political systems in forest fire management impact the effectiveness of different
      allocations. A core issue is that apparently sound management can have unintended
      consequences. An instinctive management response to periods of worsening fire
      severity is to increase fire suppression capacity, an approach with immediate
      appeal as it directly treats the symptom of devastating fires and appeases the
      public. However, the SD analysis indicates that a policy emphasizing suppression
      can degrade the long-run effectiveness of forest fire management. By crowding out
      efforts to preventative fuel removal, it exacerbates fuel loads and leads to
      greater fires, which further balloon suppression budgets. The business management
      literature refers to this problem as the firefighting trap, wherein focus on
      fixing problems diverts attention from preventing them, and thus leads to
      inferior outcomes. The paper illustrates these phenomena through a case study of
      Portugal, showing that a balanced approach to suppression and prevention efforts
      can mitigate the self-reinforcing consequences of this trap, and better manage
      long-term fire damages. These insights can help policymakers and fire managers
      better appreciate the interconnected systems in which their authorities reside
      and the dynamics that may undermine seemingly rational management decisions. 

PMID- 24036502
TI  - Anomalous interface adhesion of graphene membranes.
AB  - In order to understand the anomalous interface adhesion properties between
      graphene membranes and their substrates, we have developed a theoretical method
      to calibrate the interface adhesion energy of monolayer and multilayer graphene
      on substrates based on the bond relaxation consideration. Four kinds of
      interfaces, including graphene/SiO2, graphene/Cu, graphene/Cu/Ni and
      Cu/graphene/Ni, were taken into account. It was found that the membrane thickness
      and the interface confinement condition determine the adhesion energy. The
      relationship between the critical interface separation and the graphene thickness
      showed that the interface separation in the self-equilibrium state drops with
      decreasing membrane thickness. The size-dependent Young's modulus of graphene
      membrane and the interfacial condition were responsible for the novel interface
      adhesion energy. The proposed theory was expected to be applied to the design of
      graphene-based devices. 

PMID- 24036503
TI  - Conformational study of the structure of 18-thiacrown-6.
AB  - Conformational analysis was performed for 18-thiacrown-6 (18t6) using the CONFLEX
      method and the MMFF94s force field. Computations were performed for some of the
      low energy conformations at the HF, B3LYP, CAM-B3LYP, M06, M06L, M062x, M06HF and
      MP2 levels. The computations were also performed using the DFT-D3 method along
      with the TPSS and PBE functionals. The study predicted a new C2 conformation as
      the ground state conformation of 18t6. This new C2 conformation is more stable
      than the experimentally known solid state conformation by 4.7 kcal/mol at the
      MP2/6-311G** level. This conformation has all of the SCCS dihedral angles adopt
      exodentate structure. However, the experimentally known conformation of the solid
      phase has two of the SCCS dihedral angles violating this exodentate rule. It was
      concluded that for 18t6 stability a linear dihedral SCCS angle requirement is
      more important than a gauche CSCC dihedral angle requirement.

PMID- 24036505
TI  - 3D-QSAR analysis of TRPV1 inhibitors reveals a pharmacophore applicable to
      diverse scaffolds and clinical candidates.
AB  - TRPV1 (Transient Receptor Potential Vanilloid Type 1) receptor, a member of
      Transient Receptor Potential Vanilloid subfamily of ion channels, occurs in the
      peripheral and central nervous system, and plays a key role in transmission of
      pain. Consequently, this has been the target for discovery of several pain
      relieving agents which have undergone clinical trials. Though several TRPV1
      antagonists have progressed to become clinical candidates, many are known to
      cause temperature elevation in humans, halting their further advancement, and
      signifying the need for new chemotypes. Different chemical classes of TRPV1
      antagonists share three important features: an amide or an isostere flanked by an
      aromatic (or fused aromatic) ring with polar substitutions on one side, and a
      hydrophobic group on the other. Recent work identified new series of compounds
      with these and additional features, leading to improvement of properties, and
      development of clinical candidates. Herein, we describe a 3D-QSAR model (n=62;
      R(2)=0.9 and Q(2)=0.75) developed from the piperazinyl-aryl series of compounds
      and a novel 5-point pharmacophore model is shown to fit several diverse
      scaffolds, six clinical candidates, five pre-clinical candidates and three lead
      compounds. The pharmacophore model can aid in finding new chemotypes as starting
      points that can be developed further. 

PMID- 24036506
TI  - Predictors of hospitalization two years after treatment for first-episode
      psychosis.
AB  - OBJECTIVE This study examined the predictors of inpatient hospital admission
      after early intervention for psychosis services (EIPS) treatment. Specifically,
      the study examined the sociodemographic and clinical factors that were associated
      with hospital admissions in the two years after discharge from EIPS. METHODS The
      characteristics of 231 patients enrolled in an EIPS program in Christchurch, New
      Zealand, between 2000 and 2005 were examined. Information about post-EIPS
      hospital admissions was obtained from the New Zealand Health Information Service.
      Poisson regression models were used to estimate bivariate and multivariate
      associations between number of post-EIPS hospital admissions and a range of
      predictors, including hospitalization history. RESULTS A majority of patients
      (78%) were hospitalized before or during EIPS treatment, and 29% were
      hospitalized after the program. Older age, Maori ethnicity, a domestic
      partnership at referral, lower Global Assessment of Functioning scores, and
      hospitalization before and during treatment were significant predictors of the
      number of post-EIPS hospitalizations. CONCLUSIONS The results of the study
      suggest that the number of hospital admissions after participation in the EIPS
      program may be reduced by addressing issues related to the cultural
      appropriateness of treatment, engagement with partners and families, and overall
      adjustment and functioning and by efforts to limit hospitalization before and
      during EIPS treatment. 

PMID- 24036507
TI  - Cloning, functional characterization, and expression profiles of NADPH-cytochrome
      P450 reductase gene from the Asiatic rice striped stem borer, Chilo suppressalis
      (Lepidoptera: Pyralidae).
AB  - NADPH-cytochrome P450 reductase (CPR) is one of the most important components of
      the cytochrome P450 enzyme system. It catalyzes electron transfer from NADPH to
      all known P450s, thus plays central roles not only in the metabolism of exogenous
      xenobiotics but also in the regulation of endogenous hormones in insects. In this
      study, a full-length cDNA encoding of a CPR (named CsCPR) was isolated from the
      Asiatic rice striped stem borer, Chilo suppressalis, by using reverse
      transcription-polymerase chain reaction (RT-PCR) and rapid amplification of cDNA
      ends (RACE) methods. The cDNA contains a 2061 bp open reading frame, which
      encodes an enzyme of 686 amino acid residues, with a calculated molecular mass of
      77.6 kDa. The deduced peptide has hallmarks of typical CPR, including an N
      terminal membrane anchor and the FMN, FAD and NADPH binding domains. The N
      terminal-truncated protein fused with a 6 * His.tag was heterologously expressed
      in Escherichia coli Rosetta (DE3) cells and purified, specific activity and the
      Km values of the recombinant enzyme were determined. Tissue- and developmental
      stage-dependent expression of CsCPR mRNA was investigated by real-time
      quantitative PCR. The CsCPR mRNA was noticeably expressed in the digestive,
      metabolic, and olfactory organs of the larvae and adults of C. suppressalis. Our
      initial results would provide valuable information for further study on the
      interactions between CPR and cytochrome P450 enzyme systems.

PMID- 24036504
TI  - Reaching new levels of realism in modeling biological macromolecules in cellular
      environments.
AB  - An increasing number of studies are aimed at modeling cellular environments in a
      comprehensive and realistic fashion. A major challenge in these efforts is how to
      bridge spatial and temporal scales over many orders of magnitude. Furthermore,
      there are additional challenges in integrating different aspects ranging from
      questions about biomolecular stability in crowded environments to the description
      of reactive processes on cellular scales. In this review, recent studies with
      models of biomolecules in cellular environments at different levels of detail are
      discussed in terms of their strengths and weaknesses. In particular, atomistic
      models, implicit representations of cellular environments, coarse-grained and
      spheroidal models of biomolecules, as well as the inclusion of reactive processes
      via reaction-diffusion models are described. Furthermore, strategies for
      integrating the different models into a comprehensive description of cellular
      environments are discussed. 

PMID- 24036508
TI  - Identification of three hydroxyproline O-arabinosyltransferases in Arabidopsis
      thaliana.
AB  - Hydroxyproline (Hyp) O-arabinosylation is a post-translational modification that
      is prominent in extracellular glycoproteins in plants. Hyp O-arabinosylation is
      generally found in these glycoproteins in the form of linear oligoarabinoside
      chains and has a key role in their function by contributing to conformational
      stability. However, Hyp O-arabinosyltransferase (HPAT), a key enzyme that
      catalyzes the transfer of the L-arabinose to the hydroxyl group of Hyp residues,
      has remained undiscovered. Here, we purified and identified Arabidopsis HPAT as a
      Golgi-localized transmembrane protein that is structurally similar to the
      glycosyltransferase GT8 family. Loss-of-function mutations in HPAT-encoding genes
      cause pleiotropic phenotypes that include enhanced hypocotyl elongation, defects
      in cell wall thickening, early flowering, early senescence and impaired pollen
      tube growth. Our results indicate essential roles of Hyp O-arabinosylation in
      both vegetative and reproductive growth in plants. 

PMID- 24036509
TI  - Fluoride-dependent interruption of the transport cycle of a CLC Cl-/H+
      antiporter.
AB  - Cl(-)/H(+) antiporters of the CLC superfamily transport anions across biological
      membranes in varied physiological contexts. These proteins are weakly selective
      among anions commonly studied, including Cl(-), Br(-), I(-), NO3(-) and SCN(-),
      but they seem to be very selective against F(-). The recent discovery of a new
      CLC clade of F(-)/H(+) antiporters, which are highly selective for F(-) over Cl(
      ), led us to investigate the mechanism of Cl(-)-over-F(-) selectivity by a CLC
      Cl(-)/H(+) antiporter, CLC-ec1. By subjecting purified CLC-ec1 to anion transport
      measurements, electrophysiological recording, equilibrium ligand-binding studies
      and X-ray crystallography, we show that F(-) binds in the Cl(-) transport pathway
      with affinity similar to Cl(-) but stalls the transport cycle. Examination of
      various mutant antiporters implies a 'lock-down' mechanism of F(-) inhibition, in
      which F(-), by virtue of its unique hydrogen-bonding chemistry, greatly retards a
      proton-linked conformational change essential for the transport cycle of CLC-ec1.

PMID- 24036511
TI  - Synthesis of alpha-O- and alpha-S-glycosphingolipids related to Sphingomonous
      cell wall antigens using anomerisation.
AB  - Analogues of glycolipids from Spingomonadacaece with O- and S- and SO2-linkages
      have been prepared using chelation induced anomerisation promoted by TiCl4.
      Included are examples of the anomerisation of intermediates with O- and S
      glycosidic linkages as well as isomerisation of beta-thioglycuronic acids (beta
      glycosyl thiols). The beta-O-glucuronide and beta-O-galacturonide precursors were
      efficiently prepared using benzoylated trichloroacetimidates. beta-Glycosyl
      thiols were precursors to beta-S-derivatives. Triazole containing mimics of the
      natural glycolipids were prepared using CuI promoted azide-alkyne cycloaddition
      reactions in THF. The glycolipid antigens are being evaluated currently for their
      effects on iNKT cells.

PMID- 24036510
TI  - Insights into mucopolysaccharidosis I from the structure and action of alpha-L
      iduronidase.
AB  - Mucopolysaccharidosis type I (MPS I), caused by mutations in the gene encoding
      alpha-L-iduronidase (IDUA), is one of approximately 70 genetic disorders
      collectively known as the lysosomal storage diseases. To gain insight into the
      basis for MPS I, we crystallized human IDUA produced in an Arabidopsis thaliana
      cgl mutant. IDUA consists of a TIM barrel domain containing the catalytic site, a
      beta-sandwich domain and a fibronectin-like domain. Structures of IDUA bound to
      iduronate analogs illustrate the Michaelis complex and reveal a (2,5)B
      conformation in the glycosyl-enzyme intermediate, which suggest a retaining
      double displacement reaction involving the nucleophilic Glu299 and the general
      acid/base Glu182. Unexpectedly, the N-glycan attached to Asn372 interacts with
      iduronate analogs in the active site and is required for enzymatic activity.
      Finally, these IDUA structures and biochemical analysis of the disease-relevant
      P533R mutation have enabled us to correlate the effects of mutations in IDUA to
      clinical phenotypes. 

PMID- 24036512
TI  - Thymoquinone induces mitochondria-mediated apoptosis in acute lymphoblastic
      leukaemia in vitro.
AB  - There has been a growing interest in naturally occurring compounds from
      traditional medicine with anti-cancer potential. Nigella sativa (black seed) is
      one of the most widely studied plants. This annual herb grows in countries
      bordering the Mediterranean Sea and India. Thymoquinone (TQ) is an active
      ingredient isolated from Nigella sativa. The anti-cancer effect of TQ, via the
      induction of apoptosis resulting from mitochondrial dysfunction, was assessed in
      an acute lymphocyte leukemic cell line (CEMss) with an IC50 of 1.5 ug/mL. A
      significant increase in chromatin condensation in the cell nucleus was observed
      using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an
      increased number of cellular DNA breaks in treated cells were observed as a DNA
      ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death
      transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax.
      Moreover, the significant generation of cellular ROS, HSP70 and activation of
      caspases 3 and 8 were also observed in the treated cells. The mitochondrial
      apoptosis was clearly associated with the S phase cell cycle arrest. In
      conclusion, the results from the current study indicated that TQ could be a
      promising agent for the treatment of leukemia.

PMID- 24036513
TI  - Two new sphingolipids from the leaves of Piper betle L.
AB  - Two new sphingolipids, pipercerebrosides A (1) and B (2), were isolated from the
      leaves of Piper betle L. Their structures, including absolute configurations,
      were determined by spectroscopic analysis and chemical degradation. These two
      compounds did not show significant cytotoxic activity against the cancer cell
      lines K562 and HL-60 in a MTT assay. 

PMID- 24036514
TI  - Design and synthesis of N1,N5-bis[4-(5-alkyl-1,2,4-oxadiazol-3
      yl)phenyl]glutaramides as potential antifungal prodrugs.
AB  - A facile three step synthesis of a group of N1,N5-bis[4-(5-alkyl-1,2,4-oxadiazol
      3-yl)phenyl]glutaramides, N1,N5-bis[4-(1,2,4-oxadiazol-3-yl)phenyl]glutaramide
      and N1,N5-bis[4-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)phenyl]glutaramide is
      described. These products are designed to function as masked bis-amidine prodrugs
      of a promising N1,N5-bis[4-(N'-(carbamimidoyl)phenyl]glutaramide antifungal lead.

PMID- 24036516
TI  - Identification of multiple ingredients for a Traditional Chinese Medicine
      preparation (bu-yang-huan-wu-tang) by liquid chromatography coupled with tandem
      mass spectrometry.
AB  - Bu-yang-huan-wu-tang (BYHWT) is a popular Traditional Chinese Medicine formula
      consisting of seven herbal medicines (Astragalus membranaceus, Angelica sinensis,
      Paeonia lactiflora, Ligusticum chuanxiong, Carthamus tinctorius, Amygdalus
      persica and Pheretima aspergillum), that has been used in China for centuries to
      overcome stroke-induced disability. To ensure the consistency of quality, a
      reliable analytical method is required, therefore, we developed a liquid
      chromatography with tandem mass spectrometry (LC-MS/MS) method for quantitative
      analysis of the major constituents in BYHWT. The herbal ingredients consisting of
      the cycloartane-type triterpene glycosides of astragaloside I, astragaloside II
      and astragaloside IV; isoflavones of formononetin, ononin calycosin, calycosin-7
      O-beta-d-glucoside; ligustilide and paeoniflorin were separated on a C18 column
      with gradient elution of methanol/10 mM ammonium acetate buffer-formic acid
      (100:0.1, v/v). This study was performed by a mass spectrometer using
      electrospray ionization (ESI) with positive ionization ions monitored in the
      multiple reaction-monitoring (MRM) mode. The linearity, accuracy, precision,
      limit of detection (LOD) and lower limit of quantification (LLOQ) were validated
      for this quantification method, and the sensitivity, reliability and
      reproducibility were all confirmed. The experiments provided a good method for
      analyzing BYHWT extracts. This study also quantitated the active components in
      various brands of commercially available products. The results indicated that the
      pharmaceutical industrial products of BYHWT exhibited considerable variation in
      their contents of the herbal compounds.

PMID- 24036515
TI  - Anti-peroxyl radical quality and antibacterial properties of rooibos infusions
      and their pure glycosylated polyphenolic constituents.
AB  - The anti-peroxyl radical quality of two aqueous rooibos infusions and solutions
      of their most abundant glycosylated polyphenols was evaluated using pyrogallol
      red and fluorescein-based oxygen radical absorbance ratios. It was observed that
      the artificial infusions, prepared using only the most abundant polyphenols
      present in rooibos and at concentrations similar to those found in the natural
      infusions, showed greater antioxidant quality than the latter infusions, reaching
      values close to those reported for tea infusions. Additionally, the antimicrobial
      activity of the natural and artificial infusions was assessed against three
      species of bacteria: Gram (+) Staphylococus epidermidis and Staphylococcus aureus
      and Gram (-) Escherichia coli. When compared to the natural infusions the
      artificial beverages did not demonstrate any bacterostatic/cidal activity,
      suggesting that the antibacterial activity of rooibos is related to compounds
      other than the glycosylated polyphenols employed in our study. 

PMID- 24036518
TI  - [Charcoal, cocaine and rattlesnakes: evidence-based treatment of poisoning].
AB  - BACKGROUND: Since ancient times poisoning has been treated medicinally. Clinical
      toxicology, in the narrow sense of the term, developed from the foundation of
      specialized medical treatment units for poisoning and the formation of the first
      poison information centers in the second half of the twentieth century.
      Historically, the first poison information centers were often localized at
      pediatric clinics or departments of internal medicine. It became increasingly
      more obvious that this pooling of competences made sense. AIM: This article gives
      a general introduction in clinical toxicology and presents the functions and key
      activities of emergency poison centers. MATERIAL AND METHODS: The organisation
      and work of a poisons centre is demonstrated on the basis of the Poisons
      Information Center (GIZ) North annual report for 2011. In a short summary the
      basic principles of clinical toxicology are elucidated: the primary removal of
      poisons by gastric lavage and administration of activated charcoal, secondary
      removal of poisons by enhanced elimination using hemodialysis, hemoperfusion,
      multi-dose activated charcoal and molecular adsorbent recirculating systems
      (MARS) and the indications for administration of specific antidotes or antivenins
      (antisera against poisoning by poisonous animals). RESULTS: Gastric lavage is
      indicated within 1 h after ingestion of a potentially life-threatening dose of a
      poison. In cases of poisoning with substances which penetrate the central nervous
      system (CNS) gastric lavage should be performed only after endotracheal
      intubation due to the risk of aspiration. The basic management of poisoned
      patients by emergency medicine personnel out of hospital and on the way to
      hospital is presented. The Bremen list, a compilation of the five antidotes,
      atropine, 4-dimethylaminophenol (4-DMAP), tolonium chloride, naloxone and
      activated charcoal for out of hospital treatment by emergency doctors is
      presented. CONCLUSION: In all, even questionable cases of poisoning consultation
      at emergency poison centers is recommended. An extensive list of all German
      speaking poison information centers is available on the homepage of GIZ-Nord
      (http://www.giz-nord.de).

PMID- 24036517
TI  - QTL mapping of leukocyte telomere length in American Indians: the Strong Heart
      Family Study.
AB  - Telomeres play a central role in cellular senescence and are associated with a
      variety of age-related disorders such as dementia, Alzheimer's disease and
      atherosclerosis. Telomere length varies greatly among individuals of the same
      age, and is heritable. Here we performed a genome-wide linkage scan to identify
      quantitative trait loci (QTL) influencing leukocyte telomere length (LTL)
      measured by quantitative PCR in 3,665 American Indians (aged 14-93 years) from 94
      large, multi-generational families. All participants were recruited by the Strong
      Heart Family Study (SHFS), a prospective study to identify genetic factors for
      cardiovascular disease and its risk factors in American Indians residing in
      Oklahoma, Arizona and Dakota. LTL heritability was estimated to be between 51%
      and 62%, suggesting a strong genetic predisposition to interindividual variation
      of LTL in this population. Significant QTLs were localized to chromosome 13
      (Logarithm of odds score (LOD)=3.9) at 13q12.11, to 18q22.2 (LOD=3.2) and to
      3p14.1 (LOD=3.0) for Oklahoma. This is the first study to identify susceptibility
      loci influencing leukocyte telomere variation in American Indians, a minority
      group suffering from a disproportionately high rate of type 2 diabetes and other
      age-related disorders.

PMID- 24036519
TI  - Total absorption in asymmetric hyperbolic media.
AB  - Finite-thickness slabs of hyperbolic media with tilted optical axes exhibit
      asymmetry properties for waves propagating upward and downward with respect to
      slab interfaces. Under certain conditions, asymmetric hyperbolic media acquire
      extreme permittivity parameters and the difference between upward and downward
      propagating waves becomes very large. Furthermore, both waves can be perfectly
      matched with the free space; such a feature makes possible the development of
      optically ultra thin perfect absorbers. The proposed approach is unified and
      allows the use of different -negative materials. Of particular interest is the
      asymmetric hyperbolic medium, made of silicon nanowires, since it can be directly
      applicable to solar cell systems. 

PMID- 24036520
TI  - Spironolactone enhances the beneficial effect of aliskiren on cardiac structural
      and electrical remodeling in TGR(mRen2)27 rats.
AB  - OBJECTIVE: To investigate the influence of simultaneous administration of
      spironolactone (20 mg/kg per day, intraperitoneal (i.p.)) and aliskiren (50 mg/kg
      per day, i.p.) for a period of eight weeks on cardiac remodeling in TGR(mRen2)27
      rats. METHODS: Echocardiographic and electrophysiological and histological
      methods were used to determine the influence of spironolactone and aliskiren on
      cardiac remodeling. RESULTS: 1) the beneficial effect of aliskiren on SBP was
      enhanced by simultaneous administration of spironolactone; 2) echocardiographic
      studies showed that the left ventricle diameter (LVD), the left ventricle end
      diastolic volume (LVEDV) and the left ventricle posterior wall thickness (LVPW)
      were significantly reduced by the combination of both drugs when compared with
      aliskiren alone; 3) the ejection fraction was also increased; 4) histological
      studies indicated a greater decline in perivascular and interstitial fibrosis
      when both drugs were used; 5) the decrease of electrical remodeling of the left
      ventricle caused by aliskiren was further reduced by simultaneous administration
      of spironolactone; 6) the cardiac refractoriness increased by aliskiren was
      further incremented by spironolactone. Spironolactone (20 mg/kg per day) alone
      increased the ejection fraction and reduced LVD, LVEDV and LVPW but its effect
      was smaller than that achieved with the combination spironolactone plus
      aliskiren. CONCLUSION: The combination of an aldosterone inhibitor with a direct
      renin inhibitor proved to be of greater benefit for cardiac structural and
      electrical remodeling in this experimental model of hypertension than aliskiren
      alone.

PMID- 24036521
TI  - Fine structure and sensory apparatus of the mouthparts of the pear psyllid,
      Cacopsylla chinensis (Yang et Li) (Hemiptera: Psyllidae).
AB  - The pear psyllid, Cacopsylla chinensis (Yang et Li) (Hemiptera: Psyllidae), is
      one of the most significant economic pests of pear in China, causing direct
      damage through feeding by the highly specialized piercing-sucking mouthparts. The
      ultrastructural morphology and sensory apparatus of the mouthparts of the adult
      were examined using scanning and transmission electron microscopy. The piercing
      sucking mouthparts of C. chinensis are composed of a three-segmented labium with
      a deep groove in the anterior side, a stylet fascicle consisting of two
      mandibular and two maxillary stylets, and a pyramid-shaped labrum. Proximal to
      the labium, the stylet fascicle forms a large loop within a membranous crumena.
      Mandibles, with more than ten teeth on the external convex region, can be seen on
      the distal extremity. Smooth maxillary stylets are interlocked to form a larger
      food canal and a smaller salivary canal. One dendritic canal housing 2 dendrites
      is also found in each mandible. Two types of sensilla trichodea, four types of
      sensilla basiconica, single as well as groups of sensilla campaniformia, and oval
      flattened sensilla occur in different locations on the labium, whereas a kind of
      sensilla basiconica is at the junction of the labrum and anteclypeus. Sensilla
      trichodea and sensilla campaniformia, always present with denticles, are present
      on the middle labial segment. Three types of sensilla basiconica, two types of
      sensilla trichodea and two oval flattened sensilla are located on the distal
      labial segment. The mouthpart morphology and abundance of sensilla located on the
      labium in C. chinensis are illustrated, along with a brief discussion of their
      taxonomic and putative functional significance. 

PMID- 24036522
TI  - A nanostarch functionalized ionic liquid containing imidazolium cation and cobalt
      chelate anion for the synthesis of carbamates from amines and dimethyl carbonate.
AB  - A new nanostarch functionalized ionic liquid containing imidazolium cation and
      cobalt chelate anion was synthesized and tested for the one pot synthesis of
      carbamates by the reaction of amines and dimethyl carbonate (DMC), affording
      excellent yield of the products under solvent free mild reaction conditions. The
      synthesized ionic liquid was easily recovered and reused several times without
      any loss in catalytic efficiency. 

PMID- 24036523
TI  - Direct analysis in real time--a critical review on DART-MS.
AB  - Direct analysis in real time mass spectrometry (DART-MS) has become an
      established technique for rapid mass spectral analysis of a large variety of
      samples. DART-MS is capable of analyzing the sample at atmospheric pressure,
      essentially in the open laboratory environment. DART-MS can be applied to
      compounds that have been deposited or adsorbed on to surfaces or that are being
      desorbed therefrom into the atmosphere. This makes DART-MS suitable and well
      known for analysis of ingredients of plant materials, pesticide monitoring on
      vegetables, forensic and safety applications such as screening for traces of
      explosives, warfare agents, or illicit drugs on luggage, clothes, or bank notes,
      etc. DART can also be used for analysis of either solid or liquid bulk materials,
      as may be required in quality control, or to quickly investigate the identity of
      a compound from chemical synthesis. Even living organisms can be subjected to
      DART-MS. Driven by different needs in analytical practice, the combination of the
      DART ionization source and interface can be configured in multiple geometries and
      with various accessories to adapt the setup as required. Analysis by DART-MS
      relies on some sort of gas-phase ionization mechanism. In DART, initial
      generation of the ionizing species is by use of a corona discharge in a pure
      helium atmosphere which delivers excited helium atoms that, upon their release
      into the atmosphere, will initiate a cascade of gas-phase reactions. In the end,
      this results in reagent ions created from atmospheric water or (solvent) vapor in
      the vicinity of the surface subject to analysis where they effect a chemical
      ionization process. DART ionization processes may generate positive or negative
      ions, predominantly even-electron species, but odd-electron species do also
      occur. The prevailing process of analyte ion formation from a given sample is
      highly dependent on analyte properties. 

PMID- 24036524
TI  - Bicyclic guanidinium-catalyzed enantioselective phase-transfer alkylation: direct
      access to pyrroloindolines and furoindolines.
AB  - Highly enantioselective phase-transfer alkylation of 3-substituted-2-oxindoles
      with activated bromomethanes is disclosed with a broad substrate scope by using
      bicyclic guanidinium as a catalyst and a Lewis acid as the co-catalyst. The
      alkylation adducts are versatile intermediates to accomplish the syntheses of
      pyrroloindolines and furoindolines. 

PMID- 24036525
TI  - Design of supramolecular amino acids to template peptide folding.
AB  - We describe in this manuscript a new design of supramolecular amino acids (SAAs)
      for directing peptide folding in organic environments. The incorporated
      supramolecular motif has a strong driving force to dimerize in a sequence- and
      orientation-specific manner. By introducing such SAAs into the primary sequence
      of peptides, the specific and directional dimerization of the supramolecular
      units should facilitate the folding of the peptides. Our approach may provide a
      general strategy to program secondary structures in organic media. 

PMID- 24036526
TI  - beta-Type Zr-Nb-Ti biomedical materials with high plasticity and low modulus for
      hard tissue replacements.
AB  - In order to develop new biomedical materials for hard tissue replacements, Zr
      20Nb-xTi (x=0, 3, 7, 11 and 15) alloys with required properties were designed and
      prepared by using the vacuum arc melting method for the first time. Phase
      analysis and microstructural observation showed that all the as cast samples
      consisted of equiaxed beta-Zr phase. The mechanical properties and fracture
      behaviors of the Zr-20Nb-xTi alloys have been analyzed. It is found that these
      alloys exhibit high plasticity, moderate compressive strength (1044-1325MPa) and
      yield stress (854-1080MPa), high elastic energy (12-20MJ/m(3)) and low Young's
      modulus (28-31GPa). This good combination of mechanical properties makes them
      potential biomedical materials for hard tissue replacement. 

PMID- 24036527
TI  - Kinetic modeling of batch fermentation for Populus hydrolysate tolerant mutant
      and wild type strains of Clostridium thermocellum.
AB  - The extent of inhibition of two strains of Clostridium thermocellum by a Populus
      hydrolysate was investigated. A Monod-based model of wild type (WT) and Populus
      hydrolysate tolerant mutant (PM) strains of the cellulolytic bacterium C.
      thermocellum was developed to quantify growth kinetics in standard media and the
      extent of inhibition to a Populus hydrolysate. The PM was characterized by a
      higher growth rate (MUmax=1.223 vs. 0.571 h(-1)) and less inhibition
      (KI,gen=0.991 vs. 0.757) in 10% v/v Populus hydrolysate compared to the WT. In
      17.5% v/v Populus hydrolysate inhibition of PM increased slightly (KI,gen=0.888),
      whereas the WT was strongly inhibited and did not grow in a reproducible manner.
      Of the individual inhibitors tested, 4-hydroxybenzoic acid was the most
      inhibitory, followed by galacturonic acid. The PM did not have a greater ability
      to detoxify the hydrolysate than the WT.

PMID- 24036528
TI  - Osteoarthritis: genes, nature-nurture interaction and the role of leptin.
AB  - Osteoarthritis (OA) is a common disease affecting patients at different ages
      regardless of gender or ethnicity. As with many chronic diseases, OA is thought
      to have a multifactorial aetiology, which is not fully understood. Whereas the
      pathophysiological process of OA can be analysed at a cellular and molecular
      level, the interaction between genes and lifestyle remains an important factor in
      the development of this disease. The expanding awareness of different genes that
      may play a role in OA, together with many chemical mediators thought to be
      associated with the progression of the disease, will help in better management of
      this condition. Some of the chemical mediators recently implicated in this
      condition are the adipokines (leptin, adiponectin and resistin). Few but
      consistent studies suggest that leptin in association with obesity could be an
      important factor in OA aetiology. Hence, this could establish a strong and direct
      molecular link between patient life style (nurture) and the pathological process
      of OA (nature). However, neither a clear mechanism nor a direct clinical
      association linking leptin to OA has yet been established. In this article, we
      explore some of the genetic and environmental factors in OA aetiology. We discuss
      leptin in obesity and assess its possible association with OA aetiology. This
      should emphasise the important role of health professionals in treating obesity
      in order to control OA symptoms and possibly progression. 

PMID- 24036529
TI  - Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational
      studies.
AB  - Vitamin D is suggested to have protective effects against type 1 diabetes.
      However, the results from observational studies have been inconsistent. We aimed
      to examine their association by conducting a meta-analysis of observational
      studies. Multiple databases were searched in June 2013 to identify relevant
      studies including both case-control and cohort studies. Either a fixed- or random
      effects model was used to calculate the pooled risk estimate. We identified eight
      studies (two cohort studies and six case-control studies) on vitamin D intake
      during early life and three studies (two cohort studies and one case-control
      study) on maternal vitamin D intake during pregnancy. The pooled odds ratio for
      type 1 diabetes comparing vitamin D supplementation with non-supplementation
      during early life was 0.71 (95% confidence interval [CI], 0.51-0.98). Similar
      results were observed in the case-control subgroup analysis but not in the cohort
      subgroup analysis. The pooled odds ratio with maternal intake of vitamin D during
      pregnancy was 0.95 (95% CI, 0.66-1.36). In conclusion, vitamin D intake during
      early life may be associated with a reduced risk of type 1 diabetes. However,
      there was not enough evidence for an association between maternal intake of
      vitamin D and risk of type 1 diabetes in the offspring. 

PMID- 24036531
TI  - Genetic aspects of scurvy and the European famine of 1845-1848.
AB  - The view of scurvy being exclusively a nutritional disorder needs to be updated.
      Genetic polymorphisms of HFE and haptoglobin (Hp) may explain the geographic
      variability of mortality caused by the European famine of the mid-19th century.
      In this period, potatoes had fallen victim to the potato blight and Ireland was
      more severely hit than continental Europe. Hereditary hemochromatosis is a
      genetic disorder with mutations in the HFE gene, characterized by iron overload
      (with a reduced vitamin C stability) and with a predominance of affected men. The
      Irish have the world's highest frequency of the C282Y mutation and the particular
      iron metabolism of the Irish helps to understand the size of the catastrophe and
      the observed overrepresentation of male skeletons showing scurvy. Hp is a plasma
      alpha2-glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2
      2). When the antioxidant capacity of Hp is insufficient, its role is taken over
      by hemopexin and vitamin C. The relative number of scurvy victims corresponds
      with the Hp 2-2 frequency, which is associated with iron conservation and has an
      impact on vitamin C stability. As iron is more abundant in males, males are
      overrepresented in the group of skeletons showing scurvy signs. 

PMID- 24036532
TI  - Interventions to increase initial appointment attendance in mental health
      services: a systematic review.
AB  - OBJECTIVE Although nonattendance at initial appointments in mental health
      services is a substantial problem, the phenomenon is poorly understood. This
      review synthesized findings of randomized controlled trials (RCTs) of
      interventions to increase initial appointment attendance and determined whether
      theories or models contributed to intervention design. METHODS Six electronic
      databases were systematically searched, and reference lists of identified studies
      were also examined. Studies included were RCTs (including "quasi-randomized"
      controlled trials) that compared standard practice with an intervention to
      increase attendance at initial appointments in a sample of adults who had a
      scheduled initial appointment in a mental health or substance abuse service
      setting. RESULTS Of 144 potentially relevant studies, 21 met inclusion criteria.
      These studies were reported in 20 different research papers. Of these, 16 studies
      (N=3,673 participants) were included in the analyses (five were excluded because
      they reported only nonattendance at the initial appointment). Separate analyses
      were conducted for each intervention type (opt-in systems, telephone reminders
      and prompts, orientation and reminder letters, accelerated intake, preappointment
      completion of psychodynamic questionnaires, and "other"). Narrative synthesis was
      used for analysis because the high level of heterogeneity between studies
      precluded a meta-analysis. The results were mixed for all types of intervention.
      Some isolated high-quality studies of opt-in systems, orientation and reminder
      letters, and more novel interventions demonstrated a beneficial effect.
      CONCLUSIONS The synthesized findings indicated that orientation and reminder
      letters may have a small beneficial effect. Consistent evidence for the efficacy
      of other types of common interventions is lacking. More novel interventions, such
      as asking clients to formulate plans to deal with obstacles to attendance and
      giving clients a choice of therapist style, showed some promise, but studies
      require replication. 

PMID- 24036530
TI  - Absorption of vitamin A and carotenoids by the enterocyte: focus on transport
      proteins.
AB  - Vitamin A deficiency is a public health problem in most developing countries,
      especially in children and pregnant women. It is thus a priority in health policy
      to improve preformed vitamin A and/or provitamin A carotenoid status in these
      individuals. A more accurate understanding of the molecular mechanisms of
      intestinal vitamin A absorption is a key step in this direction. It was long
      thought that beta-carotene (the main provitamin A carotenoid in human diet), and
      thus all carotenoids, were absorbed by a passive diffusion process, and that
      preformed vitamin A (retinol) absorption occurred via an unidentified energy
      dependent transporter. The discovery of proteins able to facilitate carotenoid
      uptake and secretion by the enterocyte during the past decade has challenged
      established assumptions, and the elucidation of the mechanisms of retinol
      intestinal absorption is in progress. After an overview of vitamin A and
      carotenoid fate during gastro-duodenal digestion, our focus will be directed to
      the putative or identified proteins participating in the intestinal membrane and
      cellular transport of vitamin A and carotenoids across the enterocyte (i.e.,
      Scavenger Receptors or Cellular Retinol Binding Proteins, among others). Further
      progress in the identification of the proteins involved in intestinal transport
      of vitamin A and carotenoids across the enterocyte is of major importance for
      optimizing their bioavailability. 

PMID- 24036533
TI  - Genome signature-based dissection of human gut metagenomes to extract subliminal
      viral sequences.
AB  - Bacterial viruses (bacteriophages) have a key role in shaping the development and
      functional outputs of host microbiomes. Although metagenomic approaches have
      greatly expanded our understanding of the prokaryotic virosphere, additional
      tools are required for the phage-oriented dissection of metagenomic data sets,
      and host-range affiliation of recovered sequences. Here we demonstrate the
      application of a genome signature-based approach to interrogate conventional
      whole-community metagenomes and access subliminal, phylogenetically targeted,
      phage sequences present within. We describe a portion of the biological dark
      matter extant in the human gut virome, and bring to light a population of
      potentially gut-specific Bacteroidales-like phage, poorly represented in existing
      virus like particle-derived viral metagenomes. These predominantly temperate
      phage were shown to encode functions of direct relevance to human health in the
      form of antibiotic resistance genes, and provided evidence for the existence of
      putative 'viral-enterotypes' among this fraction of the human gut virome. 

PMID- 24036534
TI  - Molybdate:sulfate ratio affects redox metabolism and viability of the
      dinoflagellate Lingulodinium polyedrum.
AB  - Molybdenum is a transition metal used primarily (90% or more) as an additive to
      steel and corrosion-resistant alloys in metallurgical industries and its release
      into the environment is a growing problem. As a catalytic center of some redox
      enzymes, molybdenum is an essential element for inorganic nitrogen
      assimilation/fixation, phytohormone synthesis, and free radical metabolism in
      photosynthesizing species. In oceanic and estuarine waters, microalgae absorb
      molybdenum as the water-soluble molybdate anion (MoO4(2-)), although MoO4(2-)
      uptake is thought to compete with uptake of the much more abundant sulfate anion
      (SO4(2-), approximately 25 mM in seawater). Thus, those aspects of microalgal
      biology impacted by molybdenum would be better explained by considering both
      MoO4(2-) and SO4(2-) concentrations in the aquatic milieu. This work examines
      toxicological, physiological and redox imbalances in the dinoflagellate
      Lingulodinium polyedrum that have been induced by changes in the
      molybdate:sulfate ratios. We prepared cultures of Lingulodinium polyedrum grown
      in artificial seawater containing eight different MoO4(2-) concentrations (from 0
      to 200 MUM) and three different SO4(2-) concentrations (3.5 mM, 9.6 mM and 25
      mM). We measured sulfur content in cells, the activities of the three major
      antioxidant enzymes (superoxide dismutase, catalase, and ascorbate peroxidase),
      indexes of oxidative modifications in proteins (carbonyl content) and lipids
      (thiobarbituric acid-reactive substances, TBARS), the activities of the
      molybdenum-dependent enzymes xanthine oxidase and nitrate reductase, expression
      of key protein components of dinoflagellate photosynthesis (peridinin-chlorophyll
      a protein and ribulose-1,5-biphosphate carboxylase/oxidase) and growth curves. We
      find evidence for Mo toxicity at relatively high [MoO4(2-)]:[SO4(2-)] ratios. We
      also find evidence for extensive redox adaptations at Mo levels well below lethal
      levels.

PMID- 24036535
TI  - Copper interacts with nonylphenol to cancel the effect of nonylphenol on fish
      chemosensory behaviour.
AB  - The majority of ecotoxicological studies have been concerned with responses of
      organisms to a single contaminant. While this approach remains valid, the
      challenge now is to understand the way in which multiple contaminants and
      stressors interact to produce effects in study organisms. Here we take an
      integrated biological and physico-chemical approach to understand the effects of
      4-nonylphenol and copper on fish (white perch, Morone americana) chemosensory
      behaviour. We show that a one hour exposure to 2 MUg L(-1) nonylphenol removes
      chemosensory attraction to conspecific chemical cues, while exposure to 5 MUg L(
      1) copper for one hour had no significant effect on the fish's attraction to
      these cues. Further, we show that simultaneous exposure to both contaminants at
      the stated dosage and for the same duration has no significant effect on the
      chemosensory attraction of white perch to conspecific chemical cues suggesting
      that copper mediates the effect of nonylphenol on fish in this respect. Physico
      chemical data show that copper ions bind to nonylphenol in water, providing a
      mechanistic explanation for this change in the effect of nonylphenol.
      Furthermore, the finding that the copper ions bind to the lone pair of O on the
      nonylphenol molecule offers the tantalising possibility that it is this region of
      the nonylphenol molecule that plays the key role in disrupting fish chemical
      communication.

PMID- 24036536
TI  - Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell
      invasion.
AB  - The bisphosphonate zoledronic acid (ZA) significantly reduces complications of
      bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent
      clinical trials indicate additional anti-metastatic effects of ZA outside the
      bone. However, which step of metastasis is influenced and whether thisis due to
      directtoxicity on cancer cells or inhibition of the tumor promoting
      microenvironment, is unknown. In particular, tumor-associated and resident
      macrophages support each step of organ metastasis and could be a crucial target
      of ZA. Thus, we comparatively investigate the ZA effects on: i) different types
      of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced
      invasion. We demonstrate that ZA concentrations reflecting the plasma level
      affected viability of human macrophages, murine bone marrow-derived macrophages
      as well as their resident brain equivalents, the microglia, while it did not
      influence the tested cancer cells. However, the effects on the macrophages
      subsequently reduced the macrophage/microglia-induced invasiveness of the cancer
      cells. In line with this, manipulation of microglia by ZA in organotypic brain
      slice cocultures reduced the tissue invasion by carcinoma cells. The
      characterization of human macrophages after ZA treatment revealed a
      phenotype/response shift, in particular after external stimulation. In
      conclusion, we show that therapeutic concentrations of ZA affect all types of
      macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are
      predominantly caused by modulating the microenvironment. Most importantly, our
      findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells
      to the brain tissue, indicating a potential therapeutic role in the prevention of
      cerebral metastasis. 

PMID- 24036538
TI  - Ovarian follicle burnout: a universal phenomenon?

PMID- 24036539
TI  - Induction of multiple cycles of pancreatic beta-cell replacement.

PMID- 24036537
TI  - Focal adhesion complex proteins in epidermis and squamous cell carcinoma.
AB  - Focal adhesions (FAs) are large, integrin-containing, multi-protein assemblies
      spanning the plasma membrane that link the cellular cytoskeleton to surrounding
      extracellular matrix. They play critical roles in adhesion and cell signaling and
      are major regulators of epithelial homeostasis, tissue response to injury, and
      tumorigenesis. Most integrin subunits and their associated FA proteins are
      expressed in skin, and murine genetic models have provided insight into the
      functional roles of FAs in normal and neoplastic epidermis. Here, we discuss the
      roles of these proteins in normal epidermal proliferation, adhesion, wound
      healing, and cancer. While many downstream signaling mechanisms remain unclear,
      the critically important roles of FAs are highlighted by the development of
      therapeutics targeting FAs for human cancer. 

PMID- 24036540
TI  - Poisoning the "histone code" in pediatric gliomagenesis.

PMID- 24036541
TI  - The CDK-activating kinase Cdk7: taking yes for an answer.

PMID- 24036542
TI  - Aging, MnSOD, and hormesis mechanisms converge on liver mUPR.

PMID- 24036543
TI  - Laser microbeam-induced DNA damage inhibits cell division in fertilized eggs and
      early embryos.
AB  - DNA double-strand breaks are caused by both intracellular physiological processes
      and environmental stress. In this study, we used laser microbeam cut (abbreviated
      microcut or cut), which allows specific DNA damage in the pronucleus of a
      fertilized egg and in individual blastomere(s) of an early embryo, to investigate
      the response of early embryos to DNA double-strand breaks. Line type gammaH2AX
      foci were detected in the cut region, while Chk2 phosphorylation staining was
      observed in the whole nuclear region of the cut pronuclei or blastomeres. Zygotes
      with cut male or female pronucleus showed poor developmental capability: the
      percentage of cleavage embryos was significantly decreased, and the embryos
      failed to complete further development to blastocysts. The cut blastomeres in 2
      cell, 4-cell, and 8-cell embryos ceased cleavage, and they failed to incorporate
      into compacted morulae, but instead underwent apoptosis and cell death at the
      blastocyst stage; the uncut part of embryos could develop to blastocysts, with a
      reduced percentage or decreased cell number. When both blastomeres of the 2-cell
      embryos were cut by laser microbeam, cell death occurred 24 h earlier, suggesting
      important functions of the uncut blastomere in delaying cell death of the cut
      blastomere. Taken together, we conclude that microbeam-induced DNA damage in
      early embryos causes compromised development, and that embryos may have their own
      mechanisms to exclude DNA-damaged blastomeres from participating in further
      development. 

PMID- 24036544
TI  - Targeting an Achilles' heel of cancer with a WRN helicase inhibitor.
AB  - Our recently published work suggests that DNA helicases such as the Werner
      syndrome helicase (WRN) represent a novel class of proteins to target for
      anticancer therapy. Specifically, pharmacological inhibition of WRN helicase
      activity in human cells defective in the Fanconi anemia (FA) pathway of
      interstrand cross-link (ICL) repair are sensitized to the DNA cross-linking agent
      and chemotherapy drug mitomycin C (MMC) by the WRN helicase inhibitor NSC 617145.
      (1) The mechanistic basis for the synergistic interaction between NSC 617145 and
      MMC is discussed in this paper and extrapolated to potential implications for
      genetic or chemically induced synthetic lethality provoked by cellular exposure
      to the WRN helicase inhibitor under the context of relevant DNA repair
      deficiencies associated with cancers or induced by small-molecule inhibitors.
      Experimental data are presented showing that small-molecule inhibition of WRN
      helicase elevates sensitivity to MMC-induced stress in human cells that are
      deficient in both FANCD2 and DNA protein kinase catalytic subunit (DNA-PKcs).
      These findings suggest a model in which drug-mediated inhibition of WRN helicase
      activity exacerbates the deleterious effects of MMC-induced DNA damage when both
      the FA and NHEJ pathways are defective. We conclude with a perspective for the FA
      pathway and synthetic lethality and implications for DNA repair helicase
      inhibitors that can be developed for anticancer strategies. 

PMID- 24036545
TI  - Human CAF-1-dependent nucleosome assembly in a defined system.
AB  - Replication-coupled nucleosome assembly is a critical step in packaging newly
      synthesized DNA into chromatin. Previous studies have defined the importance of
      the histone chaperones CAF-1 and ASF1A, the replicative clamp PCNA, and the clamp
      loader RFC for the assembly of nucleosomes during DNA replication. Despite
      significant progress in the field, replication-coupled nucleosome assembly is not
      well understood. One of the complications in elucidating the mechanisms of
      replication-coupled nucleosome assembly is the lack of a defined system that
      faithfully recapitulates this important biological process in vitro. We describe
      here a defined system that assembles nucleosomal arrays in a manner dependent on
      the presence of CAF-1, ASF1A-H3-H4, H2A-H2B, PCNA, RFC, NAP1L1, ATP, and strand
      breaks. The loss of CAF-1 p48 subunit causes a strong defect in packaging DNA
      into nucleosomes by this system. We also show that the defined system forms
      nucleosomes on nascent DNA synthesized by the replicative polymerase delta. Thus,
      the developed system reproduces several key features of replication-coupled
      nucleosome assembly. 

PMID- 24036546
TI  - ERCC1 function in nuclear excision and interstrand crosslink repair pathways is
      mediated exclusively by the ERCC1-202 isoform.
AB  - ERCC1 (excision repair cross-complementation group 1) plays essential roles in
      the removal of DNA intrastrand crosslinks by nucleotide excision repair, and that
      of DNA interstrand crosslinks by the Fanconi anemia (FA) pathway and homology
      directed repair processes (HDR). The function of ERCC1 thus impacts on the DNA
      damage response (DDR), particularly in anticancer therapy when DNA damaging
      agents are employed. ERCC1 expression has been proposed as a predictive biomarker
      of the response to platinum-based therapy. However, the assessment of ERCC1
      expression in clinical samples is complicated by the existence of 4 functionally
      distinct protein isoforms, which differently impact on DDR. Here, we explored the
      functional competence of each ERCC1 protein isoform and obtained evidence that
      the 202 isoform is the sole one endowed with ERCC1 activity in DNA repair
      pathways. The ERCC1 isoform 202 interacts with RPA, XPA, and XPF, and XPF
      stability requires expression of the ERCC1 202 isoform (but none of the 3
      others). ERCC1-deficient non-small cell lung cancer cells show abnormal mitosis,
      a phenotype reminiscent of the FA phenotype that can be rescued by isoform 202
      only. Finally, we could not observe any dominant-negative interaction between
      ERCC1 isoforms. These data suggest that the selective assessment of the ERCC1
      isoform 202 in clinical samples should accurately reflect the DDR-related
      activity of the gene and hence constitute a useful biomarker for customizing
      anticancer therapies. 

PMID- 24036547
TI  - Somatic inactivation of Tp53 in hematopoietic stem cells or thymocytes
      predisposes mice to thymic lymphomas with clonal translocations.
AB  - TP53 protects cells from transformation by responding to stresses including
      aneuploidy and DNA double-strand breaks (DSBs). TP53 induces apoptosis of
      lymphocytes with persistent DSBs at antigen receptor loci and other genomic loci
      to prevent these lesions from generating oncogenic translocations. Despite this
      critical function of TP53, germline Tp53(-/-) mice succumb to immature T-cell
      (thymic) lymphomas that exhibit aneuploidy and lack clonal translocations.
      However, Tp53(-/-) mice occasionally develop B lineage lymphomas and Tp53
      deletion in pro-B cells causes lymphomas with oncogenic immunoglobulin (Ig) locus
      translocations. In addition, human lymphoid cancers with somatic TP53
      inactivation often harbor oncogenic IG or T-cell receptor (TCR) locus
      translocations. To determine whether somatic Tp53 inactivation unmasks
      translocations or alters the frequency of B lineage tumors in mice, we generated
      and analyzed mice with conditional Tp53 deletion initiating in hematopoietic stem
      cells (HSCs) or in lineage-committed thymocytes. Median tumor-free survival of
      each strain was similar to the lifespan of Tp53(-/-) mice. Mice with HSC deletion
      of Tp53 predominantly succumbed to thymic lymphomas with clonal translocations
      not involving Tcr loci; however, these mice occasionally developed mature B-cell
      lymphomas that harbored clonal Ig translocations. Deletion of Tp53 in thymocytes
      caused thymic lymphomas with aneuploidy and/or clonal translocations, including
      oncogenic Tcr locus translocations. Our data demonstrate that the developmental
      stage of Tp53 inactivation affects karyotypes of lymphoid malignancies in mice
      where somatic deletion of Tp53 initiating in thymocytes is sufficient to cause
      thymic lymphomas with oncogenic translocations. 

PMID- 24036548
TI  - Autophagy modulates cell migration and beta1 integrin membrane recycling.
AB  - Cell migration is dependent on a series of integrated cellular events including
      the membrane recycling of the extracellular matrix receptor integrins. In this
      paper, we investigate the role of autophagy in regulating cell migration. In a
      wound-healing assay, we observed that autophagy was reduced in cells at the
      leading edge than in cells located rearward. These differences in autophagy were
      correlated with the robustness of MTOR activity. The spatial difference in the
      accumulation of autophagic structures was not detected in rapamycin-treated
      cells, which had less migration capacity than untreated cells. In contrast, the
      knockdown of the autophagic protein ATG7 stimulated cell migration of HeLa cells.
      Accordingly, atg3(-/-) and atg5(-/-) MEFs have greater cell migration properties
      than their wild-type counterparts. Stimulation of autophagy increased the co
      localization of beta1 integrin-containing vesicles with LC3-stained autophagic
      vacuoles. Moreover, inhibition of autophagy slowed down the lysosomal degradation
      of internalized beta1 integrins and promoted its membrane recycling. From these
      findings, we conclude that autophagy regulates cell migration, a central
      mechanism in cell development, angiogenesis, and tumor progression, by mitigating
      the cell surface expression of beta1 integrins. 

PMID- 24036549
TI  - S6K in geroconversion.
AB  - Markers of cellular senescence depend in part on the MTOR (mechanistic target of
      rapamycin) pathway. MTOR participates in geroconversion, a conversion from
      reversible cell cycle arrest to irreversible senescence. Recently we demonstrated
      that hyper-induction of cyclin D1 during geroconversion was mostly dependent on
      MEK, whereas rapamycin only partially inhibited cyclin D1 accumulation. Here we
      show that, while not affecting cyclin D1, siRNA for p70S6K partially prevented
      loss of RP (replicative/regenerative potential) during p21-induced cell cycle
      arrest. Similarly, an inhibitor of p70 S6 kinase (PF-4708671) partially inhibited
      phosphorylation of S6 and preserved RP, while only marginally prevented cyclin D1
      induction. Thus S6K and MEK play different roles in geroconversion. 

PMID- 24036550
TI  - Atypical heterochromatin organization and replication are rapidly acquired by
      somatic cells following fusion-mediated reprogramming by mouse ESCs.
AB  - We recently reported that mouse embryonic stem cells (ESCs) in S/G 2 are more
      efficient at reprogramming somatic cells than ESCs at other stages of the cell
      cycle. We also provided evidence that DNA replication is induced in the nuclei of
      somatic partners upon fusion with ESC partners, and showed that this was critical
      for their conversion toward a pluripotent state. (1) Here we have used
      counterflow centrifugal elutriation to enrich for ESCs at different cell cycle
      phases, so as to examine in detail the properties of S/G 2 phase cells. This
      revealed that the replication and organization of DAPI-intense heterochromatin in
      ESCs is unusual in two respects. First, replication of heterochromatin occurred
      earlier during S phase and was associated with precocious H3S10 phosphorylation.
      Second, heterochromatin protein 1 alpha (HP1alpha), which invariably marks DAPI
      intense and H3K9me3-enriched pericentromeric domains in mouse somatic cells, (2)
      was not necessarily associated with these H3K9me3-enriched domains in
      undifferentiated ESCs. These data, which complement recent replication timing (3)
      and electron spectroscopic imaging (ESI) analyses, (4) suggest that
      heterochromatin is atypical in ESCs. Interestingly, as these unusual features
      were rapidly acquired by somatic nuclei upon ESC fusion-mediated reprogramming,
      our results suggest that fundamental changes in cell cycle structure and
      heterochromatin dynamics may be important for conferring pluripotency. 

PMID- 24036552
TI  - A new model for primary-progressive multiple sclerosis?

PMID- 24036553
TI  - Building research capacity through international partnerships.

PMID- 24036554
TI  - The social history of older age.
AB  - In the making and execution of public policy of every kind, health and welfare
      services crucially among them, a long demographic perspective is a valuable
      instrument. It becomes clear that, amid the exponential growth of world
      population, with its attendant expansion of those in the older age-group,
      survival, rather than longevity, is the key. Adopting the UK as a working model,
      the use of a social and numerical analysis by function rather than chronological
      age is advocated as a help-meet, not least because this evades some of the
      negativity with which older age is regarded. A brief summation of age prejudice
      is added as a further caution about the watchfulness necessary when in pursuit of
      social goals, such as health and welfare. 

PMID- 24036551
TI  - microRNA-mediated regulation of the tumor microenvironment.
AB  - The tumor microenvironment includes cells such as fibroblasts, immune cells,
      endothelial cells, as well as extracellular matrix (ECM), proteases, and
      cytokines. Together, these components participate in a complex crosstalk with
      neoplastic tumor cells that affects growth, angiogenesis, and metastasis.
      MicroRNAs (miRNAs) are small, non-coding RNAs involved in post-transcriptional
      regulation of gene expression and have recently emerged as important players
      involved in regulating multiple aspects of cancer biology and the tumor
      microenvironment. Differential miRNA expression in both the epithelial and
      stromal compartments of tumors compared with normal tissue suggests that miRNAs
      are important drivers of tumorigenesis and metastasis. This review article
      summarizes our current understanding of the diverse roles of miRNAs involved in
      tumor microenvironment regulation and underscores the importance of miRNAs within
      multiple cell types that contribute to the hallmarks of cancer. 

PMID- 24036555
TI  - The International Union Against Tuberculosis and Lung Disease: past, present and
      future.
AB  - The International Union Against Tuberculosis and Lung Disease (The Union) is the
      oldest international non-governmental organization involved in the fight against
      tuberculosis. This review documents the history and structure of The Union up to
      2009, and describes the achievements that have taken place in the field of
      tuberculosis and lung health. The progress made in tackling the major killer
      (pneumonia) of children less than 5 years of age, the barrier to affordable
      essential asthma medicines, the complex issue of tobacco control, the move into
      the realm of HIV and AIDS, and new ideas and activities around the increasingly
      important domain of operational research are described and discussed. Finally, as
      with many institutions that have seen a rapid phase of growth, expansion and
      decentralisation to regional offices around the world, the review highlights the
      internal strategic initiative that aims to fine-tune the organisational
      structure, clarify lines of authority, create more efficient business, human
      resource and financial systems and revise, where necessary, The Union's guiding
      mission, vision and values for the future. 

PMID- 24036556
TI  - Staple diets and duodenal ulcer prevalence.
AB  - The prevalence of duodenal ulceration in India, Africa, China and other
      developing countries is high in some regions and low in others, despite a high
      prevalence of Helicobacter pylori infection throughout the areas. This variation
      is related to the staple diet of the regions involved. In regions where, because
      of the climate, the staple food is milled white rice, wheat or maize, or cassava,
      yams,sweet potato and green bananas the prevalence of duodenal ulcer is higher
      than in regions where the staple diet is based on unrefined wheat or maize, soya,
      certain millets or pulses. These differences have been reproduced in animal
      peptic ulcer models. Using these models it has been shown that the protective
      factor against ulceration lies in the lipid fraction present in staple foods from
      the low prevalence areas. The lipid fraction not only gave protection in the
      experimental models against ulceration but also promoted healing. The pulse
      Dolichos biflorus (horse gram) gave the greatest yield of the lipid and this was
      used for further investigations. It was found that the ulceroprotective activity
      of the lipid lay in its phospholipid and sterols fractions. The presence or
      absence of protective lipid in the diet would account for the regional
      differences in duodenal ulcer prevalence. 

PMID- 24036557
TI  - Comparison and critical appraisal of dengue clinical guidelines and their use in
      Asia and Latin America.
AB  - The World Health Organization (WHO) dengue classification scheme for dengue fever
      (DF) and dengue haemorrhagic fever (DHF)/dengue shock syndrome (DSS) has been
      adopted as the standard for diagnosis, clinical management and reporting. In
      recent years, difficulties in applying the WHO case classification have been
      reported in several countries. A multicenter study was carried out in Asia and
      Latin America to analyze the variation and utility of dengue clinical guidelines
      (DCGs) taking as reference the WHO/PAHO guidelines (1994) and the WHO/SEARO
      guidelines (1998). A document analysis of 13 dengue guidelines was followed by a
      questionnaire and Focus Group discussions (FGDs) with 858 health care providers
      in seven countries. Differences in DCGs of the 13 countries were identified
      including the concept of warning signs, case classification, use of treatment
      algorithms and grading into levels of severity. The questionnaires and FGDs
      revealed (1) inaccessibility of DCGs, (2) lack of training, (3) insufficient
      number of staff to correctly apply the DCGs at the frontline and (4) the
      unavailability of diagnostic tests. The differences of the DCGs and the
      inconsistency in their application suggest a need to re-evaluate and standardise
      DCGs. This applies especially to case classification and case management. 

PMID- 24036558
TI  - Official development assistance for health-how neglected are neglected tropical
      diseases? An analysis of health financing.
AB  - The increasing amounts of official development assistance (ODA) for health have
      been aimed primarily at fighting HIV/AIDS, malaria and tuberculosis. Neglected
      tropical diseases (NTD), one of the most serious public health burdens among the
      most deprived communities, have only recently drawn the attention of major
      donors. While frequently stated, the low share of funding for NTD control
      projects has not been calculated empirically. Our analysis of ODA commitments for
      infectious disease control for the years 2003 to 2007 confirms that Development
      Assistance Committee (DAC)-countries and multilateral donors have largely ignored
      funding NTD control projects. On average, only 0.6% of total annual health ODA
      was dedicated to the fight against NTDs while the average share of control
      projects for HIV/AIDS was 36.3%, for malaria 3.6%, and for tuberculosis 2.2%.
      This allocation of health ODA does not reflect the diseases' respective health
      burdens. Furthermore, the availability of cost-efficient treatments for NTDs
      supports the call for an increase in funds dedicated to the control of NTDs. 

PMID- 24036559
TI  - The shift from public to private health care providers and malaria deaths in
      Jalpaiguri district, West Bengal, India, 2006.
AB  - We investigated an increase in malaria deaths in order to formulate control
      measures. A search of records in health care facilities for cases of death
      following fever, with a blood smear or rapid antigen test positive for Plasmodium
      falciparum, identified 77 fatalities. Of these, 72 (93%) occurred in hospitals
      (78% of which in the 24 hours following admission). Of 60 family members of the
      patients who died interviewed, 70% reported that the patient had received care
      from unqualified rural private practitioners available round the clock. Among 100
      of these rural practitioners assessed, 21% knew anti-malarial dosage and 7% knew
      malaria severity criteria. There were 65% and 42% vacancies among 240 community
      health worker and 12 microscopist positions, respectively, in the public sector
      in the area. As a result, the mean interval between active case search rounds in
      the community was 35 days (standard: 14) and the median time between blood slide
      collection and radical treatment was 12 days (standard < 2 days). Deficiencies in
      the public health system may have led to a shift towards rural practitioners.
      Poor management of malaria may have contributed to deaths. We posted
      microscopists and community health workers in the area to restore appropriate
      malaria management in the public sector. 

PMID- 24036560
TI  - Evaluation of community intervention with pit latrines for trachoma control in
      Ghana, Mali, Niger and Nigeria.
AB  - Trachoma is the leading cause of preventable blindness worldwide and is
      controlled with an integrated strategy of treatment and prevention which includes
      latrine provision and promotion. We aimed to evaluate the latrine uptake,
      construction, and usage in villages participating in latrine promotion programmes
      supported by The Carter Center in Ghana, Mali, Niger and Nigeria where 113 457
      new latrines have been reported from 2002 to 2008. In each country a two stage
      cluster random sampling design was used to select villages and households for
      evaluation. Household heads were interviewed using a standardised structured
      questionnaire and latrines were inspected. The sample included 1154 households
      (Ghana: 326; Mali: 293; Niger: 300; and Nigeria: 235). Overall, 813 (70.5%, 95%
      confidence interval [CI] 65.7-74.8) had pit latrines, ranging from 30.3% of
      households in Niger to over 92.0% of households in Ghana and Mali. Of those with
      latrines 762 (93.7%) were found to be usable and 659 (86.5%) were in use. Overall
      659/1154 (57.1%) of households in the targeted communities were using latrines at
      least 12 months after latrine promotion was initiated. Latrine promotion had been
      successful increasing access to sanitation in different country contexts and
      demonstrates the target population are willing to construct, use and maintain
      household latrines. 

PMID- 24036561
TI  - Perceptions on onchocerciasis and ivermectin treatment in rural communities in
      Uganda: implications for long-term compliance.
AB  - Registers of community-directed distributors of ivermectin for onchocerciasis
      from 2000 to 2005 were reviewed to identify people highly and poorly compliant to
      ivermectin treatment. Compliance was termed 'high' if a person took annual
      ivermectin >=4 out of 6 times and 'poor' if it was taken <4 times. Individuals
      (409 and 362 highly and poorly compliant, respectively) were interviewed on
      knowledge of onchocerciasis, severity of the disease, benefits of ivermectin
      treatment and its adverse events. Those who believed onchocerciasis to be a
      serious disease and also believed ivermectin treatment alleviated symptoms
      (71.9%), were highly compliant compared with (37.7%) who believed that
      onchocerciasis was not a serious disease and ivermectin did not alleviate
      symptoms (P < 0.001). Those who believed that ivermectin caused itchiness were
      6.1% and 39.5% of highly and poorly compliant respectively (P < 0.001). Given
      that people more highly compliant with ivermectin mass drug administration (MDA)
      appear to better recognize the severity of onchocerciasis and the salutary
      effects of ivermectin, their enthusiasm to take ivermectin should be maintained
      through regular health education on the benefits and importance of continued
      treatment, and proper management of adverse events. The conclusions drawn in this
      article may equally apply to other MDA programmes. 

PMID- 24036562
TI  - Attitude of men in Nigeria to vasectomy.
AB  - The objective of this study was to assess the attitude of men in Nigeria towards
      vasectomy as a method of family planning. This was a cross-sectional study, using
      self-administered pre-tested questionnaires containing mainly close-ended
      questions. The questionnaires were given to 146 randomly selected men. The
      responses were analyzed with descriptive statistics. Ten (6.8%) may accept
      vasectomy with the knowledge they have while 130 (89.0%) will not. Eighty-eight
      (67.7%) believe sterilization procedures should be left for women only. Vasectomy
      was viewed as castration by 55 (40.7%). Forty-three (31.2%) may consider
      vasectomy if they understand that it is not associated with problems, 82 (59.4%)
      refused while 13 (9.4%) did not know if they would ever accept the procedure.
      There was a lack of knowledge of vasectomy and attitudes towards it were based on
      myths and misconceptions regarding the procedure; some may accept it if they
      understand the safety of it. Interestingly, level of education does not improve
      vasectomy uptake. A concerted effort to involve men in reproductive health is
      needed. Interpersonal communication and counseling will greatly improve vasectomy
      uptake in developing countries. 

PMID- 24036563
TI  - Relative efficacy of repellent-treated wristbands against three major mosquito
      (Diptera: Culicidae) vectors of disease, under laboratory conditions.
AB  - A laboratory study was carried out to evaluate the relative efficacy of N-N
      diethyl-m-toluamide (DEET)- and N,N-diethyl phenylacetamide (DEPA)-treated
      wristbands against three major vector mosquitoes viz., Anopheles stephensi
      Liston, Culex quinquefasciatus Say and Aedes aegypti (L.), at two different
      concentrations viz., 1.5 and 2.0 mg/cm(2). Overall, both DEET and DEPA have shown
      various degrees of repellency impact against all three vector mosquitoes. DEET
      offered the highest 317.0 min mean complete protection against An. stephensi and
      DEPA provided 275.6 min complete protection to Cx. quinquefasciatus at 2.0
      mg/cm(2). However, DEPA-treated wristbands did not show any significant
      differences in terms of reduction of human landing rate and mean complete
      protection time against An. stephensi and Ae. aegypti between 1.5 and 2.0
      mg/cm(2). DEET demonstrated relatively higher repellency impact to vector
      mosquitoes than DEPA. However, chi(2) analysis revealed that there was no
      statistically significant difference found in repellent efficiency between DEET
      and DEPA (P = 0.924). The present study result suggests that repellent-treated
      wristbands could serve as a means of potential personal protection expedient to
      avoid insect's annoyance and reduce vector-borne disease transmission. They are
      extremely valuable whenever and wherever other kinds of personal protection
      measures are unfeasible. 

PMID- 24036564
TI  - Hearing impairment in Tanzanians with albinism.
AB  - Community-based studies have suggested that those affected with albinism, an
      important condition in East Africa, may be at a greater risk of developing
      hearing problems. This study shows that the prevalence of hearing loss is
      increased in Tanzanians with albinism and that hearing loss is associated with
      fewer years in education. 64 participants with albinism and 90 controls without
      were recruited from clinics held in the Western Kilimanjaro area. Hearing was
      evaluated using pure-tone audiometry at frequencies between 250 Hz to 8000 Hz and
      patients completed a questionnaire to evaluate their educational history. Of the
      participants with albinism, 33 (51.6% [95% CI: 39.3-63.8%]) had hearing
      impairment. This was significantly greater than the control group, where 20
      (22.2% [95% CI: 13.6-30.8%]) had a similar hearing impairment (P < 0.001). Within
      the albinism group those with hearing impairment spent a mean of 6.9 years in
      education compared with those with normal hearing who spent a mean of 8.3 years
      in education (P = 0.046). Further studies are now required to determine the cause
      of these differences. Healthcare providers should be aware of hearing impairments
      when managing those with albinism and make the appropriate specialist referrals
      if further evaluation and treatment is required. 

PMID- 24036565
TI  - Estimation of population coverage for antibiotic distribution for trachoma
      control: a comparison of methods.
AB  - Trachoma control includes mass drug administration (MDA) with antibiotics
      targeting coverage of at least 80%. Coverage is traditionally calculated by
      dividing doses distributed by population estimate, which is unreliable. We
      compared a verifiable coverage assessment method against self-reported
      participation and the traditional calculation, and examined factors associated
      with MDA participation in Akobo County, Southern Sudan. During MDA, recipients
      were marked with indelible ink and followed-up using a two-stage household
      survey: 25 clusters from three districts, and 10 households per cluster. All
      household members were enumerated; asked about self-reported participation and
      observed for indelible marks. Household heads were interviewed to assess factors
      associated with MDA. Overall 11 419 treatments were given and 1358 residents from
      247 households surveyed. By traditional methods MDA coverage was 20.9% (95% CI:
      20.6-21.3); 61.5% (95 % CI: 49.4-73.6) by self-reporting; and 37.5% (95% CI:
      25.1%-49.9%) from observed ink marks. Controlling for other factors, presence of
      a health worker (OR 2.3, 95% CI: 1.5-3.6); head of household knowledge of
      azithromycin (OR 1.6, 95% CI: 1.5-3.1); and head of household advance notice of
      MDA (OR 34.9, 18.1-66.3) were independent predictors of participation. Cluster
      randomised surveys can estimate MDA coverage better than the traditional method
      and implementation of indelible marking merits investigation. 

PMID- 24036567
TI  - Ultrafast zero balance of the oscillator-strength sum rule in graphene.
AB  - Oscillator-strength sum rule in light-induced transitions is one general form of
      quantum-mechanical identities. Although this sum rule is well established in
      equilibrium photo-physics, an experimental corroboration for the validation of
      the sum rule in a nonequilibrium regime has been a long-standing unexplored
      question. The simple band structure of graphene is an ideal system for
      investigating this question due to the linear Dirac-like energy dispersion. Here,
      we employed both ultrafast terahertz and optical spectroscopy to directly monitor
      the transient oscillator-strength balancing between quasi-free low-energy
      oscillators and high-energy Fermi-edge ones. Upon photo-excitation of hot Dirac
      fermions, we observed that the ultrafast depletion of high-energy oscillators
      precisely complements the increased terahertz absorption oscillators. Our results
      may provide an experimental priori to understand, for example, the intrinsic free
      carrier dynamics to the high-energy photo-excitation, responsible for
      optoelectronic operation such as graphene-based phototransistor or solar-energy
      harvesting devices. 

PMID- 24036568
TI  - Minimised closed circuit coronary artery bypass grafting in the elderly is
      associated with lower levels of organ-specific biomarkers: a prospective
      randomised study.
AB  - BACKGROUND: Restrictive fluid management may protect organ function and improve
      postoperative outcome in elderly coronary artery bypass grafting (CABG) patients.
      OBJECTIVE: We assessed organ-specific biomarker release to study the contribution
      of a fluid restrictive closed circuit concept to organ protection in elderly CABG
      patients. Cardiac, respiratory and abdominal organ injury was measured during and
      following minimal fluid coronary artery bypass grafting (mCABG), off-pump
      coronary artery bypass (opCAB) surgery and conventional CABG with high volume
      prime and cold crystalloid cardioplegia (cCABG). The results were related to
      differences in clinical outcome. DESIGN: Prospective randomised trial. SETTING:
      Dutch tertiary single centre study. PATIENTS: Sixty patients over 70 years of age
      (38 men and 22 women) were randomised to one of the three different techniques.
      Inclusion criteria were as follows: first time CABG, elective surgery, ejection
      fraction more than 30% and multivessel disease. Acetylsalicylic acid and
      clopidogrel administration or requiring less than three distal anastomoses were
      an exclusion. MAIN OUTCOME MEASURES: Organ-specific markers of the heart--heart
      fatty acid binding protein (HFABP), troponin T, pro-brain natriuretic peptide
      (pro-BNP) and creatinine phosphokinase (CPK), lung clara cell 16 protein,
      pneumoprotein (CC16), intestinal fatty acid binding protein (IFABP) and liver
      glutathione S-transferase (alpha-GST)--were measured perioperatively.
      Postoperative PaO2 levels, ventilation time, blood product consumption and
      adverse events were noted. RESULTS: Myocardial organ-specific biomarker troponin
      T showed significantly lower median levels during mCABG compared with the cCABG
      and opCAB groups [troponin 0.25 mg l(-1) (interquartile range, IQR 0.18 to 0.40),
      0.39 mg l(-1) (IQR 0.23 to 0.49) and 0.36 mg l(-1) (IQR 0.23 to 0.50),
      respectively (P<0.003)]. HFABP, IFABP and alpha-GST levels were significantly
      higher during cCABG compared with opCAB and mCABG [HFABP 38.6 mg l(-1) (IQR 29.6
      to 47.1), 23.3 mg l(-1) (IQR 16.5 to 31.0) and 21.1 mg l(-1) (IQR 15.7 to 28.8;
      P<0.001), IFABP 0.57 mg l(-1) (IQR 0.37 to 1.11), 0.44 mg l(-1) (IQR 0.16 to
      0.74) and 0.37 mg l(-1) (IQR 0.13 to 1.05; P<0.02) and alpha-GST 11.5 mg l(-1)
      (IQR 7.7 to 15.7), 7.0 mg l(-1) (IQR 4.5 to 13.8) and 7.3 mg l(-1) (IQR 6.2 to
      11.2), respectively (P<0.009)]. There was a trend towards higher median CC16
      levels in the cCABG group (P<0.07). CPK and pro-BNP were not significantly
      different. On the first postoperative day, PaO2 levels and duration of mechanical
      ventilation were significantly improved, and there was lower use of blood
      products in the mCABG group than in the cCABG and opCAB groups (P<0.05).
      CONCLUSION: Following mCABG with low volume myocardial preservation and
      restrictive fluid management, early respiratory performance was improved and
      consumption of blood products reduced compared with opCAB and cCABG.

PMID- 24036569
TI  - Comment on: The value of colour Doppler sonography of the knee joint: a useful
      tool to discriminate inflammatory from non-inflammatory disease?: reply.

PMID- 24036570
TI  - Comment on: The value of colour Doppler sonography of the knee joint: a useful
      tool to discriminate inflammatory from non-inflammatory disease?

PMID- 24036572
TI  - Superficial medial collateral ligament anatomic augmented repair versus anatomic
      reconstruction: an in vitro biomechanical analysis.
AB  - BACKGROUND: When surgical intervention is required for a grade 3 superficial
      medial collateral ligament (sMCL) tear, there is no consensus on the optimal
      surgical treatment. Anatomic augmented repairs and anatomic reconstructions for
      treatment of grade 3 sMCL tears have not been biomechanically validated or
      compared. HYPOTHESIS: Anatomic sMCL augmented repairs and anatomic sMCL
      reconstruction techniques will reproduce equivalent knee kinematics when compared
      with the intact state, while creating significant improvements in translational
      and rotational laxity compared with the sMCL sectioned state. STUDY DESIGN:
      Controlled laboratory study. METHODS: Eighteen match-paired, fresh-frozen
      cadaveric knees (average age, 52.6 years; range, 40-59 years) were each used to
      test laxity of an intact sMCL, a deficient sMCL, and either an anatomic augmented
      repair or an anatomic reconstruction. Knees were biomechanically tested in a 6
      degrees of freedom robotic system, which included valgus rotation, internal and
      external rotation, simulated pivot shift, and coupled anterior drawer with
      external rotation. RESULTS: Anatomic augmented repairs and anatomic
      reconstructions had significantly less medial joint gapping than the sectioned
      state at all tested flexion angles and showed significant reductions in valgus
      rotation compared with the sectioned state at all flexion angles. No significant
      differences between the anatomic augmented repair and anatomic reconstruction
      were found for any test performed. Despite the similar behavior between the 2
      reconstruction groups, neither technique was able to reproduce the intact state.
      CONCLUSION: Anatomic sMCL augmented repairs and anatomic sMCL reconstructions
      were not significantly different when tested at time zero. Both the anatomic
      augmented repair and the anatomic reconstruction were able to improve knee
      stability and provide less than 2 mm of medial joint gapping at 0 degrees  and 20
      degrees  of flexion. CLINICAL SIGNIFICANCE: These results suggest that both an
      anatomic sMCL augmented repair and an anatomic sMCL reconstruction improve knee
      kinematics compared with a deficient sMCL and provide equivalent joint stability.

PMID- 24036571
TI  - Posterior tibial slope and further anterior cruciate ligament injuries in the
      anterior cruciate ligament-reconstructed patient.
AB  - BACKGROUND: An injury to the anterior cruciate ligament (ACL) is a multifactorial
      event influenced by intrinsic and extrinsic risk factors. Recently, the geometry
      of the proximal tibia has come under focus as a possible risk factor for an ACL
      injury. HYPOTHESIS: An increased posterior tibial slope is associated with an
      increased risk of further ACL injuries in the previously ACL-reconstructed
      patient. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A total
      of 200 consecutive patients with isolated ACL ruptures who underwent primary
      reconstruction with hamstring autografts were enrolled in a prospective
      longitudinal study over 15 years. The posterior tibial slope was measured from a
      lateral knee radiograph by 2 blinded observers. The data were analyzed for the
      association between an increased posterior tibial slope and the incidence of
      further ACL injuries. Interobserver reliability of the posterior tibial slope
      measurements was assessed. RESULTS: Radiographs and follow-up were available for
      181 of the 200 enrolled patients. Fifty patients had a further injury to either
      the ACL graft or the contralateral knee. The mean posterior tibial slope of those
      with a further ACL injury was 9.9 degrees  compared with 8.5 degrees  for those
      with no further injury (P = .001). The mean posterior tibial slope for those with
      both an ACL graft and contralateral ACL rupture was 12.9 degrees . The odds of
      further ACL injuries after reconstruction were increased by a factor of 5, to an
      incidence of 59%, in those with a posterior tibial slope of >=12 degrees .
      CONCLUSION: An increased posterior tibial slope is associated with increased odds
      of a further ACL injury after ACL reconstruction. The increased risk is most
      pronounced in those with a posterior tibial slope of >=12 degrees .

PMID- 24036574
TI  - Fabrication of metal-organic framework nanosheets and nanorolls with N-donor type
      bridging ligands.
AB  - Nanosheets and nanorolls of a metal-organic framework (MOF) with N-donor type
      neutral bridging ligands were obtained from a layered copper-based MOF by
      exfoliation treatment in wet process, and were characterized by TEM, SEM, and
      AFM. The thinnest nanosheet indicates monolayer thickness of the mother MOF. 

PMID- 24036573
TI  - Risk factors for meniscectomy after meniscal repair.
AB  - BACKGROUND: Previous research suggests that a substantial percentage of meniscal
      repairs fail, resulting in a subsequent meniscectomy. Risk factors for failure
      have been investigated using small cohorts, providing ambiguous results. PURPOSE:
      To measure the frequency of and elucidate risk factors for subsequent
      meniscectomies after meniscal repair using a large study population from multiple
      surgical centers. STUDY DESIGN: Case-control study; Level of evidence, 3.
      METHODS: A total of 9529 patients who underwent 9609 outpatient meniscal repairs
      between 2003 and 2010 were identified from a statewide database of all ambulatory
      surgery in New York. Patients who subsequently underwent a meniscectomy were then
      identified. A Cox regression analysis was used to calculate the hazard ratio and
      95% confidence intervals. The model included patient age, sex, comorbidities,
      concomitant arthroscopic procedures, laterality of the meniscus, and surgeon's
      yearly meniscal repair volume. RESULTS: The overall frequency of subsequent
      meniscectomies was 8.9%. Patients were at a decreased risk for subsequent
      meniscectomies if they underwent a concomitant anterior cruciate ligament (ACL)
      reconstruction (P < .001). Patients undergoing isolated meniscal repairs (without
      concomitant ACL reconstruction) were at a decreased risk if they were older (P <
      .001), had a lateral meniscal injury (P = .002), or were operated on by a surgeon
      with a higher annual meniscal repair volume (>24 cases/year; P < .001).
      CONCLUSION: A meniscectomy after meniscal repair is performed infrequently,
      supporting the notion that repairing a meniscus is a safe and effective procedure
      in the long term. The risk for undergoing subsequent meniscectomies is decreased
      in patients undergoing a concomitant ACL reconstruction, in cases of isolated
      meniscal repairs for patients of older age, and in patients undergoing meniscal
      repair by surgeons with a high case volume.

PMID- 24036576
TI  - A heterogeneous layered bifunctional catalyst for the integration of aerobic
      oxidation and asymmetric C-C bond formation.
AB  - The design and synthesis of a heterogeneous bifunctional chiral catalyst for the
      sequential aerobic oxidation-asymmetric Michael reactions between primary allylic
      alcohols and dibenzyl malonate are described. Interestingly, we found that
      layering bimetallic nanoparticles over the organocatalyst, within the chiral
      composite material, is crucial for catalytic activity. 

PMID- 24036575
TI  - Chicken beta-globin insulators fail to shield the nkx2.5 promoter from
      integration site effects in zebrafish.
AB  - Genetic lineage tracing and conditional mutagenesis are developmental genetics
      techniques reliant on precise tissue-specific expression of transgenes. In the
      mouse, high specificity is usually achieved by inserting the transgene into the
      locus of interest through homologous recombination in embryonic stem cells. In
      the zebrafish, DNA containing the transgenic construct is randomly integrated
      into the genome, usually through transposon-mediated transgenesis. Expression of
      such transgenes is affected by regulatory features surrounding the integration
      site from general accessibility of chromatin to tissue-specific enhancers. We
      tested if the 1.2 kb cHS4 insulators derived from the chicken beta-globin locus
      can shield a transgene from chromosomal position effects in the zebrafish genome.
      As our test promoters, we used two different-length versions of the zebrafish
      nkx2.5. We found that flanking a transgenic construct by cHS4 insulation
      sequences leads to overall increase in the expression of nkx2.5:mRFP. However, we
      also observed a very high degree of variability of mRFP expression, indicating
      that cHS4 insulators fail to protect nkx2.5:mRFP from falling under the control
      of enhancers in the vicinity of integration site. 

PMID- 24036577
TI  - Light driven water oxidation by a single site cobalt salophen catalyst.
AB  - A salophen cobalt(II) complex enables water oxidation at neutral pH in
      photoactivated sacrificial cycles under visible light, thus confirming the high
      appeal of earth abundant single site catalysis for artificial photosynthesis.

PMID- 24036578
TI  - Acute aggravation of subdural fluid collection associated with dural metastasis
      of malignant neoplasms: case report and review of the literature.
AB  - A 63-year-old woman was admitted to our hospital with serious headache and
      vomiting. Five months before admission, she had undergone surgery for a primary
      advanced gastric cancer. Neuroradiological examinations revealed subdural fluid
      collection. We twice performed evacuation of the subdural fluid collection.
      However, aggravation of her state of consciousness progressed and she passed
      away. Histological examinations demonstrated that the dural veins were
      infiltrated by numerous tumor cells that produced mucus; however, ruptured
      vessels were not found. Furthermore, the subdural fluid collection increased
      shortly after the initial operation. We infer that the cause of the collection,
      which was associated with the dural metastasis of malignant tumors, was not only
      mucin secretion by tumor cells but also a rapid increase in perfusion pressure in
      the vessels of the dura mater, resulting in extravasation of plasma components
      into the subdural space. Our case demonstrates that the pathogenetic mechanism
      that is specific for subdural fluid collection caused by dural metastasis of
      malignant tumors differs from the mechanism of production of subdural hematoma
      associated with dural metastasis. 

PMID- 24036580
TI  - Ferritin in the antiphospholipid syndrome and its catastrophic variant (cAPS).
AB  - BACKGROUND: Ferritin is an iron storage protein considered also as an acute phase
      reactant with high levels in various inflammatory conditions. Recently, a
      plausible role for ferritin in the pathogenesis of immune-mediated and especially
      autoimmune diseases has been suggested. However, the link between ferritin and
      the antiphospholipid syndrome (APS) has been rarely explored. Therefore, in the
      current study we evaluated ferritin levels and their correlation to clinical and
      serological manifestations in patients with APS. We further analyzed ferritin
      levels among patients with the catastrophic variant of APS (cAPS). METHODS:
      Ferritin levels were determined in serum samples of 176 APS patients and 98
      matched healthy controls according to age and sex (LIAISON, DiaSorin, Italy). APS
      samples were further analyzed for antiphospholipid (anti-cardiolipin, anti- beta
      2-glycoprotein, lupus anticoagulant) and anti-infectious antibodies (CMV, EBV,
      rubella, toxoplasma, HBV) (LIAISON, DiaSorin, Italy). Clinical, serological and
      demographic manifestations were recorded. An additional analysis of ferritin
      levels among 14 patients with cAPS was performed. RESULTS: Hyperferritinemia was
      present in 9% vs. 0% of APS patients and controls, respectively (p < 0.001).
      Among patients with APS, ferritin levels correlated with venous thrombosis,
      cardiac, neurological, and hematological manifestations and the presence of anti
      CMV-IgM antibodies. Hyperferritinemia was present in 71% of cAPS patients, and
      ferritin levels among this subgroup were significantly higher compared with APS
      non-cAPS patients (816 +/- 847 ng/ml vs. 120 +/- 230 ng/ml, p < 0.001).
      CONCLUSIONS: Herein, we found that hyperferritinemia correlates with the presence
      of APS, its clinical manifestations and specifically with the catastrophic
      variant of this disease. Hyperferritinemia was also linked with anti-CMV
      antibodies among patients with APS. These associations allude to a pathogenic
      role of ferritin in the pathogenesis of APS, and the plausible role of ferritin
      as a marker of ensuing cAPS, although further studies are needed to elucidate
      these associations.

PMID- 24036581
TI  - Fast thermal calibration of low-grade inertial sensors and inertial measurement
      units.
AB  - The errors of low-cost inertial sensors, especially Micro-Electro Mechanical
      Systems (MEMS) ones, are highly dependent on environmental conditions such as the
      temperature. Thus, there is a need for the development of accurate and reliable
      thermal compensation models to reduce the impact of such thermal drift of the
      sensors. Since the conventional thermal calibration methods are typically time
      consuming and costly, an efficient thermal calibration method to investigate the
      thermal drift of a full set of gyroscope and accelerometer errors (i.e., biases,
      scale factor errors and non-orthogonalities) over the entire temperature range in
      a few hours is proposed. The proposed method uses the idea of the Ramp method,
      which removes the time-consuming process of stabilizing the sensor temperature,
      and addresses its inherent problems with several improvements. We change the
      temperature linearly for a complete cycle and take a balanced strategy by making
      comprehensive use of the sensor measurements during both heating and cooling
      processes. Besides, an efficient 8-step rotate-and-static scheme is designed to
      further improve the calibration accuracy and efficiency. Real calibration tests
      showed that the proposed method is suitable for low-grade IMUs and for both lab
      and factory calibration due to its efficiency and sufficient accuracy. 

PMID- 24036582
TI  - MARS, a multi-agent system for assessing rowers' coordination via motion-based
      stigmergy.
AB  - A crucial aspect in rowing is having a synchronized, highly-efficient stroke.
      This is very difficult to obtain, due to the many interacting factors that each
      rower of the crew must perceive. Having a system that monitors and represents the
      crew coordination would be of great help to the coach during training sessions.
      In the literature, some methods already employ wireless sensors for capturing
      motion patterns that affect rowing performance. A challenging problem is to
      support the coach's decisions at his same level of knowledge, using a limited
      number of sensors and avoiding the complexity of the biomechanical analysis of
      human movements. In this paper, we present a multi-agent information-processing
      system for on-water measuring of both the overall crew asynchrony and the
      individual rower asynchrony towards the crew. More specifically, in the system,
      the first level of processing is managed by marking agents, which release marks
      in a sensing space, according to the rowers' motion. The accumulation of marks
      enables a stigmergic cooperation mechanism, generating collective marks, i.e.,
      short-term memory structures in the sensing space. At the second level of
      processing, information provided by marks is observed by similarity agents, which
      associate a similarity degree with respect to optimal marks. Finally, the third
      level is managed by granulation agents, which extract asynchrony indicators for
      different purposes. The effectiveness of the system has been experimented on real
      world scenarios. The study includes the problem statement and its
      characterization in the literature, as well as the proposed solving approach and
      initial experimental setting. 

PMID- 24036583
TI  - Analytic performance prediction of track-to-track association with biased data in
      multi-sensor multi-target tracking scenarios.
AB  - An analytic method for predicting the performance of track-to-track association
      (TTTA) with biased data in multi-sensor multi-target tracking scenarios is
      proposed in this paper. The proposed method extends the existing results of the
      bias-free situation by accounting for the impact of sensor biases. Since little
      insight of the intrinsic relationship between scenario parameters and the
      performance of TTTA can be obtained by numerical simulations, the proposed
      analytic approach is a potential substitute for the costly Monte Carlo simulation
      method. Analytic expressions are developed for the global nearest neighbor (GNN)
      association algorithm in terms of correct association probability. The
      translational biases of sensors are incorporated in the expressions, which
      provide good insight into how the TTTA performance is affected by sensor biases,
      as well as other scenario parameters, including the target spatial density, the
      extraneous track density and the average association uncertainty error. To show
      the validity of the analytic predictions, we compare them with the simulation
      results, and the analytic predictions agree reasonably well with the simulations
      in a large range of normally anticipated scenario parameters. 

PMID- 24036584
TI  - Visible light communication system using an organic bulk heterojunction
      photodetector.
AB  - A visible light communication (VLC) system using an organic bulk heterojunction
      photodetector (OPD) is presented. The system has been successfully proven indoors
      with an audio signal. The emitter consists of three commercial high-power white
      LEDs connected in parallel. The receiver is based on an organic photodetector
      having as active layer a blend of poly(3-hexylthiophene) (P3HT) and phenyl C61
      butyric acid methyl ester (PCBM). The OPD is opto-electrically characterized,
      showing a responsivity of 0.18 A/W and a modulation response of 790 kHz at -6 V. 

PMID- 24036585
TI  - Optimal sensor arrangements in Angle of Arrival (AoA) and range based
      localization with linear sensor arrays.
AB  - This paper investigates the linear separation requirements for Angle-of-Arrival
      (AoA) and range sensors, in order to achieve the optimal performance in
      estimating the position of a target from multiple and typically noisy sensor
      measurements. We analyse the sensor-target geometry in terms of the Cramer-Rao
      inequality and the corresponding Fisher information matrix, in order to
      characterize localization performance with respect to the linear spatial
      distribution of sensors. Here in this paper, we consider both fixed and
      adjustable linear sensor arrays. 

PMID- 24036586
TI  - Currents induced by injected charge in junction detectors.
AB  - The problem of drifting charge-induced currents is considered in order to predict
      the pulsed operational characteristics in photo-and particle-detectors with a
      junction controlled active area. The direct analysis of the field changes induced
      by drifting charge in the abrupt junction devices with a plane-parallel geometry
      of finite area electrodes is presented. The problem is solved using the one
      dimensional approach. The models of the formation of the induced pulsed currents
      have been analyzed for the regimes of partial and full depletion. The obtained
      solutions for the current density contain expressions of a velocity field
      dependence on the applied voltage, location of the injected surface charge domain
      and carrier capture parameters. The drift component of this current coincides
      with Ramo's expression. It has been illustrated, that the synchronous action of
      carrier drift, trapping, generation and diffusion can lead to a vast variety of
      possible current pulse waveforms. Experimental illustrations of the current pulse
      variations determined by either the rather small or large carrier density within
      the photo-injected charge domain are presented, based on a study of Si detectors.

PMID- 24036587
TI  - Quorum sensing modulates transcription of cpsQ-mfpABC and mfpABC in Vibrio
      parahaemolyticus.
AB  - Vibrio parahaemolyticus AphA and OpaR are the two master regulators of quorum
      sensing (QS) that are abundantly produced and operate at low cell density (LCD)
      and high cell density (HCD), respectively, with an outcome of reciprocally
      gradient production of these two proteins with transition between LCD and HCD.
      The cpsQ-mfpABC gene cluster is transcribed as two operons cpsQ-mfpABC and mfpABC
      in V. parahaemolyticus. MfpABC is a putative membrane fusion transporter that
      contributes to biofilm development. CpsQ is a c-di-GMP-binding regulator that
      activates the expression of capsular polysaccharide genes and mfpABC and, thus,
      induces biofilm development. As shown in this study, OpaR and AphA bind to the
      promoter region of mfpABC to enhance and repress its transcription, respectively.
      In contrast, the positive and negative regulation of cpsQ-mfpABC by AphA and
      OpaR, respectively, achieves probably through acting of AphA or OpaR on
      additional unknown regulator(s) of cpsQ-mfpABC. The transcriptional levels of
      cpsQ-mfpABC and mfpABC enhance gradually with transition from LCD to HCD due to
      the above reciprocal regulatory action of OpaR and AphA. Data presented here
      present a novel paradigm of combined action of the two master QS regulators in
      controlling expression of the QS regulon members. 

PMID- 24036588
TI  - In-line digital holographic microscopy using a consumer scanner.
AB  - We demonstrate an in-line digital holographic microscopy using a consumer
      scanner. The consumer scanner can scan an image with 4,800 dpi. The pixel pitch
      is approximately 5.29 MUm. The system using a consumer scanner has a simple
      structure, compared with synthetic aperture digital holography using a camera
      mounted on a two-dimensional moving stage. In this demonstration, we captured an
      in-line hologram with 23, 602 * 18, 023 pixels (~0.43 gigapixels). The physical
      size of the scanned hologram is approximately 124 mm * 95 mm. In addition, to
      accelerate the reconstruction time of the gigapixel hologram and decrease the
      amount of memory for the reconstruction, we applied the band-limited double-step
      Fresnel diffraction to the reconstruction.

PMID- 24036589
TI  - Does response on the PHQ-9 Depression Questionnaire predict subsequent suicide
      attempt or suicide death?
AB  - OBJECTIVE As use of standard depression questionnaires in clinical practice
      increases, clinicians will frequently encounter patients reporting thoughts of
      death or suicide. This study examined whether responses to the Patient Health
      Questionnaire for depression (PHQ-9) predict subsequent suicide attempt or
      suicide death. METHODS Electronic records from a large integrated health system
      were used to link PHQ-9 responses from outpatient visits to subsequent suicide
      attempts and suicide deaths. A total of 84,418 outpatients age >=13 completed
      207,265 questionnaires between 2007 and 2011. Electronic medical records,
      insurance claims, and death certificate data documented 709 subsequent suicide
      attempts and 46 suicide deaths in this sample. RESULTS Cumulative risk of suicide
      attempt over one year increased from .4% among outpatients reporting thoughts of
      death or self-harm "not at all" to 4% among those reporting thoughts of death or
      self-harm "nearly every day." After adjustment for age, sex, treatment history,
      and overall depression severity, responses to item 9 of the PHQ-9 remained a
      strong predictor of suicide attempt. Cumulative risk of suicide death over one
      year increased from .03% among those reporting thoughts of death or self-harm
      ideation "not at all" to .3% among those reporting such thoughts "nearly every
      day." Response to item 9 remained a moderate predictor of subsequent suicide
      death after the same factor adjustments. CONCLUSIONS Response to item 9 of the
      PHQ-9 for depression identified outpatients at increased risk of suicide attempt
      or death. This excess risk emerged over several days and continued to grow for
      several months, indicating that suicidal ideation was an enduring vulnerability
      rather than a short-term crisis. 

PMID- 24036590
TI  - [Video-based self-control in surgical teaching. A new tool in a new concept].
AB  - BACKGROUND: Image and video-based results and process control are essential tools
      of a new teaching concept for conveying surgical skills. The new teaching concept
      integrates approved teaching principles and new media. METHOD: Every performance
      of exercises is videotaped and the result photographically recorded. The quality
      of the process and result becomes accessible for an analysis by the teacher and
      the student/learner. The learner is instructed to perform a criteria-based self
      analysis of the video and image material by themselves. RESULTS: The new learning
      concept has so far been successfully applied in seven rounds within the newly
      designed modular class "Intensivkurs Chirurgische Techniken" (Intensive training
      of surgical techniques). Result documentation and analysis via digital picture
      was completed by almost every student. The quality of the results was high.
      Interestingly the result quality did not correlate with the time needed for the
      exercise. The training success had a lasting effect. CONCLUSION: The new and
      elaborate concept improves the quality of teaching. In the long run resources for
      patient care should be saved when training students according to this concept
      prior to performing tasks in the operating theater. These resources should be
      allocated for further refining innovative teaching concepts.

PMID- 24036591
TI  - Voluntary muscle and motor cortical activation during progressive exercise and
      passively induced hyperthermia.
AB  - This study examined whether central fatigue was exacerbated by an increase in
      muscle contractile speed caused by passive hyperthermia (PaH) and whether
      exercise-induced hyperthermia (ExH) combined with related peripheral fatigue
      influenced this response. The ExH was induced by cycling at 60% of maximal oxygen
      uptake in 38 degrees C conditions and the PaH by sitting in a 48 degrees C
      climate chamber. Ten men performed brief (~ 5 s) and sustained (30 s) maximal
      voluntary isometric contractions (MVCs) of the knee extensors at baseline (CON,
      ~37.1 degrees C) and during moderate (MOD, ~ 38.5 degrees C) and severe (SEV,
      ~39.5 degrees C) hyperthermia. Motor nerve and transcranial magnetic stimulation
      were used to assess voluntary muscle and cortical activation level, along with
      contractile properties. Brief MVC force decreased to a similar extent during SEV
      ExH (-8%) and SEV-PaH (-6%; P < 0.05 versus CON). Sustained MVC force also
      decreased during MOD-ExH (-10%), SEV-ExH (-13%) and SEV-PaH (-7%; P < 0.01 versus
      CON). Motor nerve and cortical activation were reduced on reaching MOD (~ 3%) and
      SEV (~ 5%) ExH and PaH during the brief and sustained MVCs (P < 0.01 versus CON).
      Peak twitch force decreased on reaching SEV-ExH and SEV-PaH (P < 0.05 versus
      CON). Following transcranial magnetic stimulation, during the brief and sustained
      MVCs the peak muscle relaxation rate increased in ExH and PaH (P < 0.01 versus
      CON). The increase was greatest during the sustained contraction in SEV-PaH (P <
      0.01), but this did not exacerbate central fatigue relative to ExH. These results
      indicate that during fatiguing cycling exercise in the heat, quadriceps peak
      relaxation rate increases. However, the centrally mediated rate of activation
      appears sufficient to overcome even the largest increase in muscle relaxation
      rate, seen during SEV-PaH.

PMID- 24036592
TI  - Upregulation of a local renin-angiotensin system in the rat carotid body during
      chronic intermittent hypoxia.
AB  - The carotid body (CB) plays an important role in the alteration of
      cardiorespiratory activity in chronic intermittent hypoxia (IH) associated with
      sleep-disordered breathing, which may be mediated by local expression of the
      renin-angiotensin system (RAS). We hypothesized a pathogenic role for IH-induced
      RAS expression in the CB. The CB expression of RAS components was examined in
      rats exposed to IH resembling a severe sleep-apnoeic condition for 7 days. In
      situ hybridization showed an elevated expression of angiotensinogen in the CB
      glomus cells in the hypoxic group when compared with the normoxic control group.
      Immunohistochemical studies and Western blot analysis revealed increases in the
      protein level of both angiotensinogen and angiotensin II type 1 (AT1) receptors
      in the hypoxic group, which were localized to the glomic clusters containing
      tyrosine hydroxylase. RT-PCR studies confirmed that levels of the mRNA expression
      of angiotensinogen, angiotensin-converting enzyme, AT1a and AT2 receptors were
      significantly increased in the CBs of the hypoxic rats. Functionally, the
      [Ca(2+)]i response to exogenous angiotensin II was enhanced in fura-2-loaded
      glomus cells dissociated from hypoxic rats when compared with those of the
      normoxic control animals. Pretreatment with losartan, but not PD123319, abolished
      the angiotensin II-induced [Ca(2+)]i response, suggesting an involvement of AT1
      receptors. Moreover, daily treatment of the IH group of rats with losartan
      attenuated the levels of oxidative stress, gp91(phox) expression and macrophage
      infiltration in the CB. Collectively, the upregulated local RAS expression could
      play a pathogenic role in the augmented CB activity and local inflammation via
      AT1 receptor activation during IH conditions in patients with sleep-disordered
      breathing. 

PMID- 24036593
TI  - The stimulating effect of ghrelin on gastric motility and firing activity of
      gastric-distension-sensitive hippocampal neurons and its underlying regulation by
      the hypothalamus.
AB  - Ghrelin is an acylated peptide originally identified in the rat stomach as the
      endogenous ligand for growth hormone secretagogue receptor (GHSR) that promotes
      gastric motility. Our aims were to explore the effects of ghrelin on gastric
      distension-sensitive neurons in the hippocampus and the potential for ghrelin to
      regulate gastric motility through the arcuate nucleus (Arc). Single-unit
      discharges in the hippocampus were recorded extracellularly, and gastric motility
      in conscious rats was monitored. The expression of GHSR-1a in the hippocampus was
      determined by PCR, Western blot and fluo-immunohistochemistry staining.
      Retrograde tracing and fluo-immunohistochemistry staining were used to determine
      ghrelin neuron projection. Ghrelin-Fluoro-Gold double-labelled neurons and GHSR
      1a expression were observed in the Arc and hippocampus, respectively. There were
      gastric-distension-sensitive neurons in the hippocampus that could be excited by
      ghrelin or by electrical stimulation of the Arc. The excitatory effects could be
      blocked completely or partly by pretreatment with the ghrelin receptor antagonist
      [d-Lys-3]-GHRP-6. Gastric motility was significantly promoted by the
      administration of ghrelin into the hippocampus in a dose-dependent manner that
      could be completely abolished by [d-Lys-3]-GHRP-6. Electrical stimulation of the
      Arc could promote gastric motility as well. Nevertheless, these effects could be
      mitigated by pretreatment with [d-Lys-3]-GHRP-6. Electrical lesioning of the
      hippocampus diminished the excitatory effects on gastric motility that were
      induced by electrical stimulation the Arc. Our findings suggest that ghrelin
      plays an important role in promoting gastric motility via the hippocampus. The
      Arc may be involved in regulation of the influence of the hippocampus on gastric
      motility.

PMID- 24036594
TI  - The influence of gap junction network complexity on pulmonary artery smooth
      muscle reactivity in normoxic and chronically hypoxic conditions.
AB  - Experiments on intrapulmonary arteries (IPAs) isolated from rats maintained in
      normoxia and chronic hypobaric hypoxia showed that in normoxia, the IPA
      contractile sensitivity to KCl was not modified by gap junction inhibition. In
      contrast, chronic hypoxia induced an endothelium-independent hypersensitivity,
      which was suppressed by gap junction inhibition. For the theoretical analysis of
      these results, we developed a model of interconnected myocytes. Given that smooth
      muscle cells in IPAs are known to communicate via gap junctions, we regard the
      cytoarchitecture of the IPA as a spatial network, in which nodes represent
      individual smooth muscle cells and the links signify intercellular communication.
      A single-cell model that drives the dynamics of individual nodes includes the
      major elements of voltage-dependent Ca(2+) signalling. In addition,
      interindividual variability of SMCs is introduced by distributing the reversal
      potentials for K(+). Cell-to-cell connection consists of passive Ca(2+) diffusion
      and electrical coupling, and connection between cells is determined by the
      topology of the intercellular network. Model predictions indicate that the
      experimental results can be explained by topological modifications and not by
      changes in the number of gap junctions. According to the model, in normoxia the
      myocytes are connected in a complex network, whereas chronic hypoxia is related
      to loss of complexity, leading to hypersensitivity. Our results thus indicate
      that chronic hypoxia entails gap junction network rearrangements, leading to
      disturbances in the intercellular communication pathways. 

PMID- 24036596
TI  - Epigenetic programming of neuroendocrine systems during early life.
AB  - Arginine vasopressin plays a pivotal role in the control of long-lasting effects
      of early-life stress on the brain. We previously reported that maternal
      separation in mice persistently upregulates Avp gene expression associated with
      reduced DNA methylation of a region in the Avp enhancer. This early-life stress
      responsive region serves as a binding site for the methyl-CpG binding protein 2,
      which in turn is controlled through neuronal activity. We also found that the
      ability of methyl-CpG binding protein 2 to regulate transcription of the Avp gene
      and induce DNA methylation occurred through the recruitment of components of the
      epigenetic machinery. Understanding the sequential events involved in the
      epigenetic regulation of a gene should allow for targeted approaches aimed at
      reprogramming expression during development and possibly later life.

PMID- 24036595
TI  - Exercise reveals impairments in left ventricular systolic function in patients
      with metabolic syndrome.
AB  - Metabolic syndrome (MetS) is the manifestation of a cluster of cardiovascular
      risk factors and is associated with a threefold increase in the risk of
      cardiovascular morbidity and mortality, which is suggested to be mediated, in
      part, by resting left ventricular (LV) systolic dysfunction. However, to what
      extent resting LV systolic function is impaired in MetS is controversial, and
      there are no data indicating whether LV systolic function is impaired during
      exercise. Accordingly, the objective of this study was to examine comprehensively
      the LV and arterial responses to exercise in individuals with MetS without
      diabetes and/or overt cardiovascular disease in comparison to a healthy control
      population. Cardiovascular function was characterized using Doppler
      echocardiography and gas exchange in individuals with MetS (n = 27) versus
      healthy control subjects (n = 20) at rest and during peak exercise. At rest,
      individuals with MetS displayed normal LV systolic function but reduced LV
      diastolic function compared with healthy control subjects. During peak exercise,
      individuals with MetS had impaired contractility, pump performance and
      vasodilator reserve capacity versus control subjects. A blunted contractile
      reserve response resulted in diminished arterial-ventricular coupling reserve and
      limited aerobic capacity in individuals with MetS versus control subjects. These
      findings are of clinical importance, because they provide insight into the
      pathophysiological changes in MetS that may predispose this population of
      individuals to an increased risk of cardiovascular morbidity and mortality. 

PMID- 24036598
TI  - Uniform M3PMo12O40.nH2O (M = NH4+, K+, Cs+) rhombic dodecahedral nanocrystals for
      effective antibacterial agents.
AB  - Uniform M3PMo12O40.nH2O (M = NH(4+), K(+), Cs(+)) rhombic dodecahedral
      nanocrystals are successfully obtained using mild hydrothermal conditions or room
      temperature chemical precipitation method for their self-organization. The
      reaction temperatures and times play important roles in the possible growth
      proceeding of these nanostructures. Interestingly, from antibacterial testing,
      the nanostructured products show more effective antibacterial activity than that
      of the corresponding commercial products. Among these antibacterial
      nanomaterials, (NH4)3[PMo12O40].nH2O rhombic dodecahedral nanocrystals show
      strong inhibition of the proliferation of E. coli during the whole 48 h culture
      period, which makes it a promising antibacterial material for practical
      applications. 

PMID- 24036597
TI  - The cardiovascular actions of fractalkine/CX3CL1 in the hypothalamic
      paraventricular nucleus are attenuated in rats with heart failure.
AB  - The paraventricular nucleus (PVN) of the hypothalamus plays an important role in
      the regulation of sympathetic nerve activity, which is significantly elevated in
      chronic heart failure (CHF). Fractalkine (FKN) and its cognate receptor, CX3CR1,
      are constitutively expressed in the central nervous system, but their role and
      physiological significance are not well known. The aims of the present study were
      to determine whether FKN plays a cardiovascular role within the PVN and to
      investigate how the actions of FKN might be altered in CHF. We show that both FKN
      and CX3CR1 are expressed on neurons in the PVN of rats, suggesting that they may
      have a physiological function in this brain nucleus. Unilateral microinjection of
      FKN directly into the PVN of anaesthetized rats elicited a significant dose
      related decrease in blood pressure (1.0 nmol, -5 +/- 3 mmHg; 2.5 nmol, -13 +/- 2
      mmHg; 5.0 nmol, -22 +/- 3 mmHg; and 7.5 nmol, -32 +/- 3 mmHg) and a concomitant
      increase in heart rate (1.0 nmol, 6 +/- 3 beats min(-1); 2.5 nmol, 11 +/- 3 beats
      min(-1); 5 nmol, 18 +/- 4 beats min(-1); and 7.5 nmol, 27 +/- 5 beats min(-1))
      compared with control saline microinjections. In order to determine whether FKN
      signalling is altered in rats with CHF, we first performed quantitative RT-PCR
      and Western blot analysis and followed these experiments with functional studies
      in rats with CHF and sham-operated control rats. We found a significant increase
      in CX3CR1 mRNA and protein expression, as determined by quantitative RT-PCR and
      Western blot analysis, respectively, in the PVN of rats with CHF compared with
      sham-operated control rats. We also found that the blood pressure effects of FKN
      (2.5 nmol in 50 nl) were significantly attenuated in rats with CHF (change in
      mean arterial pressure, -6 +/- 3 mmHg) compared with sham-operated control rats
      (change in mean arterial pressure, -16 +/- 6 mmHg). These data suggest that FKN
      and its receptor, CX3CR1, modulate cardiovascular function at the level of the
      PVN and that the actions of FKN within this nucleus are altered in heart failure.

PMID- 24036599
TI  - Methane emissions and production potentials of forest swamp wetlands in the
      Eastern Great Xing'an Mountains, Northeast China.
AB  - Measurements of methane flux at a few inundated sites in China have been
      extrapolated to obtain estimates on a national scale. To enable those national
      estimates to be refined and to compare flux from geographically separated sites
      comprising the same wetland types, we used a closed chamber method to measure
      methane flux in uninundated Betula platyphylla-and Larix gmelinii-dominated
      peatlands in the Northeast China. Our measurements were taken from both vegetated
      and bare soil surfaces, and we compared flux with environmental measures
      including vegetation biomass, soil temperature and soil characteristics. We found
      that methane flux was low, and that there were no significant differences between
      wetland types, indicating that environmental influences were dominant. We found
      that flux was positively correlated to temperature in the surface layers of the
      soil, the above-ground biomass of the shrub and herb layers, total soil carbon
      and total soil nitrogen; and we suggest that emissions may be due to anaerobic
      microcosms in the surface layers. The methane production potentials of the soils
      were low and similar between both sites but inconsistent with the differences
      between fluxes, and inconsistent with production potentials and fluxes reported
      from the same wetland types elsewhere, indicating that there were subtle
      environmental differences between wetlands classed as being of the same type.
      Differences between fluxes in vegetated chambers with bare soil chambers were
      insignificant, indicating that no methane emission through aerenchyma occurred at
      our sites. We concluded that wetland type was not an accurate predictor of
      methane flux. 

PMID- 24036600
TI  - Visitor assessment of the mandatory alternative transportation system at Zion
      National Park.
AB  - Transportation infrastructure in national parks has historically been designed
      for the automobile. With more vehicles in the parks, visitors found themselves in
      circumstances more reminiscent of a city than a park. Traffic jams, overcrowding,
      illegal parking, horn honking, and idling vehicles became common, creating stress
      and contributing to air and noise pollution, the very things visitors were hoping
      to get away from. Park managers began searching for alternatives, including
      shuttle systems. Many national parks have implemented optional shuttle systems,
      but relatively few have completely closed roads to vehicles, transporting
      visitors on mandatory shuttles. Zion National Park instituted a mandatory shuttle
      system in May 2000 to relieve crowding and congestion in the main canyon and to
      protect natural resources. Taking a longitudinal approach, attributes of the
      shuttle (e.g., crowding, accessibility, freedom, efficiency, preference, and
      success) were assessed with experiential park factors (e.g., scenic beauty,
      naturalness, solitude, tranquility, air quality, and soundscape) in 2000, 2003,
      and 2010 by surveying shuttle-riding park visitors. While visitors initially
      reported a few reservations about the shuttle system, by 2003, the majority rated
      the system successful. Ratings of all shuttle-related variables, except crowding,
      improved over the decade. Improvements were greatest for freedom, accessibility,
      and efficiency. Multiple regression found overall shuttle success to be mediated
      by preference, freedom, accessibility, efficiency, and comfort. Experiential
      variables assessing park conditions followed a similar pattern, with improved
      ratings as the decade progressed. Results provide important insights into the
      visitor experience with mandatory alternative shuttle systems in national parks. 

PMID- 24036601
TI  - Movement of the lumbar spine is critical for maintenance of postural recovery
      following support surface perturbation.
AB  - Repeated measures design. This study examined recovery of postural equilibrium
      (centre of pressure (COP) excursion, time to recover balance, and the number of
      postural adjustments) following unexpected support surface perturbation in
      healthy participants with and without a rigid lumbar corset to reduce lumbar
      motion. Lumbar spine movement is thought to aid postural stability, especially
      when a "hip" (lumbopelvic) strategy is required, such as in response to large and
      fast perturbations. Delayed onset of lumbar spine movement in association with
      prolonged postural recovery in chronic low back pain implies reduced spinal
      motion could underpin balance deficits in this group. However, other explanations
      such as poor proprioception cannot be excluded, and the relationship between
      lumbar movement and postural stability remains unclear. We hypothesized
      restricted lumbar spine movement would impair control of postural recovery
      following support surface perturbation. Participants regained postural stability
      following unexpected support surface perturbations in different directions
      (forward and backward), with different amplitudes (small, medium, and large),
      with and without restriction of spine motion by a hard lumbar corset. Although
      the latency of the postural adjustment was unaffected by the corset, the quality
      of postural recovery was compromised (increased COP range, time taken for
      postural recovery, and number of postural adjustments) during recovery,
      especially in response to large perturbation. Restriction of lumbar spine
      movement adversely affects postural recovery. The results suggest movement of the
      lumbar spine, although small in amplitude, is critical for efficient recovery of
      standing balance. 

PMID- 24036602
TI  - Illusory rotation in the haptic perception of a moving bar.
AB  - Haptic matching of the orientation of bars separated by a horizontal distance
      leads to large systematic deviations. This finding leads to the following
      intriguing question which we investigated in this study: How will a bar moving
      from left to right in a fixed orientation be perceived by blindfolded observers?
      Interestingly, this previous finding predicts that the translating bar will cause
      the illusory perception of a rotation. In our experiment, we used psychophysical
      methods to determine the rotation needed to perceive the bar as non-rotating, for
      both rightward and leftward translations. From our results, it can be estimated
      that, on average, a bar translating in parallel over 60 cm is perceived as
      rotating 18 degrees , so we established that the predicted illusory rotation
      indeed exists. This implies that static and dynamic signals are processed in a
      similar way. 

PMID- 24036603
TI  - Osmium isotope evidence for a large Late Triassic impact event.
AB  - Anomalously high platinum group element concentrations have previously been
      reported for Upper Triassic deep-sea sediments, which are interpreted to be
      derived from an extraterrestrial impact event. Here we report the osmium (Os)
      isotope fingerprint of an extraterrestrial impact from Upper Triassic chert
      successions in Japan. Os isotope data exhibit a marked negative excursion from an
      initial Os isotope ratio ((187)Os/(188)Osi) of ~0.477 to unradiogenic values of
      ~0.126 in a platinum group element-enriched claystone layer, indicating the input
      of meteorite-derived Os into the sediments. The timing of the Os isotope
      excursion coincides with both elevated Os concentrations and low Re/Os ratios.
      The magnitude of this negative Os isotope excursion is comparable to those found
      at Cretaceous-Paleogene boundary sites. These geochemical lines of evidence
      demonstrate that a large impactor (3.3-7.8 km in diameter) produced a global
      decrease in seawater (187)Os/(188)Os ratios in the Late Triassic. 

PMID- 24036604
TI  - The AKT inhibitor MK-2206 is cytotoxic in hepatocarcinoma cells displaying
      hyperphosphorylated AKT-1 and synergizes with conventional chemotherapy.
AB  - Hepatocellular carcinoma (HCC) is one of the most common potentially lethal human
      malignancies worldwide. Advanced or recurrent HCC is frequently resistant to
      conventional chemotherapeutic agents and radiation. Therefore, targeted agents
      with tolerable toxicity are mandatory to improve HCC therapy and prognosis. In
      this neoplasia, the PI3K/Akt signaling network has been frequently shown to be
      aberrantly up-regulated. To evaluate whether Akt could represent a target for
      treatment of HCC, we studied the effects of the allosteric Akt inhibitor, MK
      2206, on a panel of HCC cell lines characterized by different levels of Akt-1
      activation. The inhibitor decreased cell viability and induced cell cycle arrest
      in the G0/G1 phase of the cell cycle, with a higher efficacy in cells with
      hyperphosphorylated Akt-1. Moreover, MK-2206 induced apoptosis, as documented by
      Annexin V labeling, and also caused autophagy, as evidenced by increased levels
      of the autophagy marker LC3A/B. Autophagy was shown to be a protective mechanism
      against MK-2206 cytotoxicity. MK-2206 down-regulated, in a concentration
      dependent manner, the phosphorylation levels of Akt-1 and its downstream targets,
      GSK3 alpha/beta and FOXO3A. MK-2206 synergized with doxorubicin, a
      chemotherapeutic drug widely used for HCC treatment. Our findings suggest that
      the use of Akt inhibitors, either alone or in combination with doxorubicin, may
      be considered as an attractive therapeutic regimen for the treatment of HCC. 

PMID- 24036605
TI  - Initial human feasibility of infusion needle catheter ablation for refractory
      ventricular tachycardia.
AB  - BACKGROUND: Ablation of ventricular tachycardia (VT) is sometimes unsuccessful
      when ablation lesions are of insufficient depth to reach arrhythmogenic
      substrate. We report the initial experience with the use of a catheter with an
      extendable/retractable irrigated needle at the tip capable of intramyocardial
      mapping and ablation. METHODS AND RESULTS: Sequential consenting patients with
      recurrent VT underwent ablation with the use of a needle-tipped catheter. At
      target sites, the needle was advanced 7 to 9 mm into the myocardium, permitting
      pacing and recording. Infusion of saline/iodinated contrast mixture excluded
      perforation and ensured intramyocardial deployment. Further infusion was
      delivered before and during temperature-controlled radiofrequency energy delivery
      through the needle. All 8 patients included (6 male; mean age, 54) with a mean
      left ventricular ejection fraction of 29% were refractory to multiple
      antiarrhythmic drugs, and 1 to 4 previous catheter ablation attempts (epicardial
      in 4) had failed. Patients had 1 to 7 (median, 2) VTs present or inducible; 2
      were incessant. Some intramyocardial VT mapping was possible in 7 patients. A
      mean of 22 (limits, 3-48) needle ablation lesions were applied in 8 patients. All
      patients had at least 1 VT terminated or rendered noninducible. During a median
      of 12 months follow-up, 4 patients were free of recurrent VT, and 3 patients were
      improved, but had new VTs occur at some point during follow-up. Two died of the
      progression of preexisting heart failure without recurrent VT. Complications
      included tamponade in 1 patient and heart block in 2 patients. CONCLUSIONS:
      Intramyocardial infusion-needle catheter ablation is feasible and permits control
      of some VTs that have been refractory to conventional catheter ablation therapy,
      warranting further study.

PMID- 24036606
TI  - Intramyocardial adiposity after myocardial infarction: new implications of a
      substrate for ventricular tachycardia.
AB  - BACKGROUND: Collagen has been attributed as the principal structural substrate of
      ventricular tachycardia (VT) after myocardial infarction (MI), even though
      adiposity of myocardium after MI is well recognized histologically. We
      investigated the effects of intramyocardial adiposity compared with collagen on
      electrophysiological properties, connexin43 expression, and VT induction after
      MI. METHODS AND RESULTS: Simultaneous left ventricular plunge-needle, noncontact
      mapping was performed in sheep without MI (MI-; n=5), with MI and inducible VT
      (MI+VT+; n=7), and with MI and no inducible VT (MI+VT-; n=8). Histological
      intramyocardial quantity of adipose and collagen and degree of discontinuity were
      coregistered with electrophysiological parameters (MI+; 290 specimens).
      Additional assessment of connexin43 expression was performed. Left ventricular
      scar contained a body mass-independent abundance of adipocytes
      (adipose:collagen=0.8). Increased adipose density and discontinuity contributed
      to a greater inverse correlation (r) with conduction velocity (r for
      adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram
      amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68)
      compared with collagen. Collagen density was similar between the MI+ groups
      (P>0.29). However, the MI+VT+ group demonstrated a significant (all P<=0.01)
      increase in adipose (8%) and discontinuity (qualitative) and decrease in
      conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared
      with the MI+VT- group. In scar, myocytes adjacent to fibrofatty interfaces
      demonstrated increased connexin43 lateralization. A gradient increase in adipose
      was observed at sites that supported preferential presystolic VT activation and
      exhibited attenuation of excitation wavelength (P<0.001). CONCLUSIONS:
      Intramyocardial adiposity, in association with myocardial discontinuity within
      left ventricular scar borders, is a significant factor associated with altered
      electrophysiological properties, aberrant connexin43 expression, and increased
      propensity for VT after MI.

PMID- 24036607
TI  - Automated external defibrillators inaccessible to more than half of nearby
      cardiac arrests in public locations during evening, nighttime, and weekends.
AB  - BACKGROUND: Despite wide dissemination, use of automated external defibrillators
      (AEDs) in community settings is limited. We assessed how AED accessibility
      affected coverage of cardiac arrests in public locations. METHODS AND RESULTS: We
      identified cardiac arrests in public locations (1994-2011) in terms of location
      and time and viewed them in relation to the location and accessibility of all
      AEDs linked to the emergency dispatch center as of December 31, 2011, in
      Copenhagen, Denmark. AED coverage of cardiac arrests was defined as cardiac
      arrests within 100 m (109.4 yd) of an AED and further categorized according to
      AED accessibility at the time of cardiac arrest. Daytime, evening, and nighttime
      were defined as 8 am to 3:59 pm, 4 to 11:59 pm, and midnight to 7:59 am,
      respectively. Of 1864 cardiac arrests in public locations, 61.8% (n=1152)
      occurred during the evening, nighttime, or weekends. Of 552 registered AEDs, 9.1%
      (n=50) were accessible at all hours, and 96.4% (n=532) were accessible during the
      daytime on all weekdays. Regardless of AED accessibility, 28.8% (537 of 1864) of
      all cardiac arrests were covered by an AED. Limited AED accessibility decreased
      coverage of cardiac arrests by 4.1% (9 of 217) during the daytime on weekdays and
      by 53.4% (171 of 320) during the evening, nighttime, and weekends. CONCLUSIONS:
      Limited AED accessibility at the time of cardiac arrest decreased AED coverage by
      53.4% during the evening, nighttime, and weekends, which is when 61.8% of all
      cardiac arrests in public locations occurred. Thus, not only strategic placement
      but also uninterrupted AED accessibility warrant attention if public-access
      defibrillation is to improve survival after out-of-hospital cardiac arrest.

PMID- 24036608
TI  - Long-term outcomes of dilated cardiomyopathy diagnosed during childhood: results
      from a national population-based study of childhood cardiomyopathy.
AB  - BACKGROUND: Existing studies of childhood dilated cardiomyopathy deal mainly with
      early survival. This population-based study examines long-term outcomes for
      children with dilated cardiomyopathy. METHODS AND RESULTS: The diagnosis of
      dilated cardiomyopathy was based on clinical, echocardiographic, and pathological
      findings. The primary study end point included time to the combined outcome of
      death or cardiac transplantation. There were 175 patients 0 to <10 years of age
      at the time of diagnosis. Survival free from death or transplantation was 74%
      (95% confidence interval, 67-80) 1 year after diagnosis, 62% (95% confidence
      interval, 55-69) at 10 years, and 56% (95% confidence interval, 46-65) at 20
      years. In multivariable analysis, age at diagnosis <4 weeks or >5 years, familial
      cardiomyopathy, and lower baseline left ventricular fractional shortening Z score
      were associated with increased risk of death or transplantation, as was lower
      left ventricular fractional shortening Z score during follow-up. At 15 years
      after diagnosis, echocardiographic normalization had occurred in 69% of surviving
      study subjects. Normalization was related to higher baseline left ventricular
      fractional shortening Z score, higher left ventricular fractional shortening Z
      score during follow-up, and greater improvement in left ventricular fractional
      shortening Z score. Children with lymphocytic myocarditis had better survival and
      a higher rate of echocardiographic normalization. At the latest follow-up, 100 of
      104 of survivors (96%) were free of cardiac symptoms, and 83 (80%) were no longer
      receiving pharmacotherapy. CONCLUSIONS: Death or transplantation occurred in 26%
      of patients with childhood dilated cardiomyopathy within 1 year of diagnosis and
      ~1% per year thereafter. Risk factors for death or transplantation include age at
      diagnosis, familial cardiomyopathy, and severity of left ventricular dysfunction.
      The majority of surviving subjects are well and free of cardiac medication.

PMID- 24036609
TI  - Arsenic, tobacco smoke, and occupation: associations of multiple agents with lung
      and bladder cancer.
AB  - BACKGROUND: Millions of people worldwide are exposed to arsenic in drinking
      water, and many are likely coexposed to other agents that could substantially
      increase their risks of arsenic-related cancer. METHODS: We performed a case
      control study of multiple chemical exposures in 538 lung and bladder cancer cases
      and 640 controls in northern Chile, an area with formerly high drinking water
      arsenic concentrations. Detailed information was collected on lifetime arsenic
      exposure, smoking, secondhand smoke, and other known or suspected carcinogens,
      including asbestos, silica, and wood dust. RESULTS: Very high lung and bladder
      cancer odds ratios (ORs), and evidence of greater than additive effects, were
      seen in people exposed to arsenic concentrations >335 ug/L and who were tobacco
      smokers (OR = 16, 95% confidence interval = 6.5-40 for lung cancer; and OR = 23
      [8.2-66] for bladder cancer; Rothman Synergy Indices = 4.0 [1.7-9.4] and 2.0
      [0.92-4.5], respectively). Evidence of greater than additive effects were also
      seen in people coexposed to arsenic and secondhand tobacco smoke and several
      other known or suspected carcinogens, including asbestos, silica, and wood dust.
      CONCLUSIONS: These findings suggest that people coexposed to arsenic and other
      known or suspected carcinogens have very high risks of lung or bladder cancer.

PMID- 24036610
TI  - Prenatal bisphenol a urine concentrations and early rapid growth and overweight
      risk in the offspring.
AB  - BACKGROUND: Increasing experimental evidence suggests that prenatal bisphenol A
      (BPA) exposure induces offspring weight gain, but these effects remain largely
      unexplored in humans. We examined the effects of prenatal BPA exposure on
      postnatal growth and obesity. METHODS: BPA concentrations were measured in two
      spot-urine samples collected in the 1st and 3rd trimesters of pregnancy from
      mothers in a Spanish birth cohort study (n = 402). We used the average of the two
      creatinine-adjusted BPA concentrations as the exposure variable. Rapid child
      growth was defined as a weight gain Z score >0.67 in the first 6 months of life.
      Age- and sex-specific Z scores for body mass index (BMI) were calculated at age
      14 months and 4 years, based on the World Health Organization referent;
      overweight was defined as a BMI Z score greater than or equal to the 85th
      percentile. Age- and sex-specific waist circumference Z scores were calculated at
      age 14 months and 4 years using the analysis population mean. RESULTS: Twenty-six
      percent of children were rapid growers; 25% were overweight at 14 months and 21%
      at 4 years. Geometric mean BPA concentrations were 2.6 MUg/g creatinine (standard
      deviation = 2.3) in 1st trimester and 2.0 (2.3) in 3rd trimester samples (Pearson
      r = 0.13). At 4 years, BPA exposure was associated with increased waist
      circumference (beta per log10 MUg/g = 0.28 [95% confidence interval = 0.01 to
      0.57]) and BMI (beta = 0.28 [-0.06 to 0.63]). BPA was not associated with obesity
      related outcomes at earlier ages. CONCLUSIONS: This study provides some evidence
      for an association between prenatal BPA exposure and obesity-related outcomes in
      childhood, although not in infancy. The large uncertainties in BPA exposure
      assessment require that findings be interpreted with caution.

PMID- 24036611
TI  - Perfluorinated compound levels in cord blood and neurodevelopment at 2 years of
      age.
AB  - BACKGROUND: Epidemiologic data regarding the potential neurotoxicity of
      perfluorinated compounds (PFCs) are inconclusive. We investigated the
      associations between in utero exposure to perfluorooctanoic acid (PFOA) and
      perfluorooctyl sulfonate (PFOS) and early childhood neurodevelopment. METHODS: We
      recruited 239 mother-infant pairs in northern Taiwan from the Taiwan Birth Panel
      Study, which was established in 2004. We examined the association between PFCs in
      cord blood and children's neurodevelopment at 2 years of age, using the
      Comprehensive Developmental Inventory for Infants and Toddlers. This tool
      contains cognitive, language, motor, social, and self-help domains; test scores
      were further transformed into developmental quotients according to standardized
      norms. All multivariate regression models were adjusted for infant sex and
      gestational age, maternal education, family income, cord blood cotinine levels,
      postnatal environmental tobacco smoke exposure, and breastfeeding. RESULTS:
      Prenatal PFOS concentrations in both untransformed and natural log (Ln)
      transformed values were associated with adverse performance on the whole test and
      the domains related to development. A dose-response relationship was observed
      when PFOS levels were categorized into four groups. This association was most
      obvious in relation to the gross-motor subdomain. Across the PFOS interquartile
      range, the quotients of the gross-motor subdomain decreased by 3.7 points (95%
      confidence interval [CI] = -6.0 to -1.5), with an increasing odds ratio of poor
      performance (2.4; 95% CI = 1.3 to 4.2). In contrast, measures of association
      between PFOA concentrations and test scores were close to null. CONCLUSIONS:
      Prenatal exposure to PFOS, but not PFOA, may affect children's development,
      especially gross-motor development at 2 years of age.

PMID- 24036612
TI  - Thiazole as a weak electron-donor unit to lower the frontier orbital energy
      levels of donor-acceptor alternating conjugated materials.
AB  - We demonstrate that the substitution of the thiophene by the thiazole
      heterocyclic compound as a weak electron-donor unit, in donor-acceptor
      alternating conjugated materials, allows a simultaneous downshift of both HOMO
      and LUMO levels while keeping the energy bandgap almost unchanged. 

PMID- 24036613
TI  - Periarticular infiltration for pain relief after total hip arthroplasty: a
      comparison with epidural and PCA analgesia.
AB  - PURPOSE: Epidural and intravenous patient-controlled analgesia (PCA) are
      established methods for pain relief after total hip arthroplasty (THA).
      Periarticular infiltration is an alternative method that is gaining ground due to
      its simplicity and safety. Our study aims to assess the efficacy of periarticular
      infiltration in pain relief after THA. METHODS: Sixty-three patients undergoing
      THA under spinal anaesthesia were randomly assigned to receive postoperative
      analgesia with continuous epidural infusion with ropivacaine (epidural group),
      intraoperative periarticular infiltration with ropivacaine, clonidine, morphine,
      epinephrine and corticosteroids (infiltration group) or PCA with morphine (PCA
      group). PCA morphine provided rescue analgesia in all groups. We recorded
      morphine consumption, visual analog scale (VAS) scores at rest and movement,
      blood loss from wound drainage, mean arterial pressure (MAP) and adverse effects
      at 1, 6, 12, 24 h postoperatively. RESULTS: Morphine consumption at all time
      points, VAS scores at rest, 6, 12 and 24 h and at movement, 6 and 12 h
      postoperatively were lower in infiltration group compared to PCA group (p <
      0.05), but did not differ between infiltration and epidural group. There was no
      difference in adverse events in all groups. At 24 h, MAP was higher in the PCA
      group (p < 0.05) and blood loss was lower in the infiltration group (p < 0.05).
      CONCLUSIONS: In our study periarticular infiltration was clearly superior to PCA
      with morphine after THA, providing better pain relief and lower opioid
      consumption postoperatively. Infiltration seems to be equally effective to
      epidural analgesia without having the potential side effects of the latter.

PMID- 24036614
TI  - Regulation of cell shape and adhesion by CD34.
AB  - We previously reported that expression of CD43/leukosialin induces cell rounding
      and microvillus formation via inhibition of cell adhesion. Here, we found that
      CD34, a cell surface sialomucin and marker for hematopoietic progenitor cells,
      also inhibited cell adhesion and induced cell rounding and microvillus formation.
      Forced expression of CD34-induced cell rounding, microvillus formation, and
      phosphorylation of ezrin/radixin/moesin (ERM) proteins in HEK293T cells, while
      inhibiting integrin-mediated cell re-attachment. Furthermore, CD34+ blood cells
      and KG-1 cells, which express endogenous CD34 on their surface, were spherical in
      shape, surrounded by microvilli, and non-adherent to substrata. In addition,
      cleavage of O-sialomucin augmented integrin-mediated cell adhesion of KG-1 cells.
      These results suggest the involvement of CD34 in the inhibition of integrin
      mediated cell adhesion and formation of the cell surface structure. The
      inhibitory function of CD34 in cell adhesion may affect cell shape organization
      via phosphorylation of ERM proteins. Cellular structures such as the spherical
      shape and microvilli of CD34+ cells may also contribute to regulation of cell
      adhesion. 

PMID- 24036615
TI  - Anti-hyperglycemic effect of bilberry, blackberry and mulberry ultrasonic
      extracts on diabetic rats.
AB  - Small fruits like bilberry, blackberry and mulberry are rich sources of
      anthocyanins and other phenols, compounds with a certified antioxidant activity
      and spectacular effects in some chronic diseases. Romanian bilberry, blackberry
      and mulberry extracts were tested as anti-hyperglycemic agents on diabetic rats.
      Anthocyanins extraction was carried out with 80 % acidified ethanol in
      ultrasonically conditions at 23 +/- 2  degrees C and 40 kHz. Monomeric
      anthocyanins content was determined by pH differential method and varied between
      1200 and 2800 mg/L. The analyses of anthocyanins were achieved using high
      performance liquid chromatography and mass spectrometry. Phenolics content was
      determined by Folin-Ciocalteu procedure and values varied between 2320 and 4250
      mg/L gallic acid. Antioxidant activities of extracts were estimated by DPPH
      scavenging method and the values varied between 8 and 16 miliequivalents Trolox.
      In order to evaluate the toxicology of the extracts, the heavy metals
      concentration and pesticides content were analyzed. The extracts were
      administrated to diabetic rats in drinking water for five weeks. The
      administration of bilberry extract offered no satisfactory results. Treatment
      with blackberry extract determined a significant decrease of glucose level from
      360 to about 270 mg/dL (p < 0.05). The mulberry extract administration determined
      a significant decrease of glucose level from 252 mg/dL at the start day to 155
      mg/dL at the final of experiment (p < 0.05). 

PMID- 24036616
TI  - Additional indications for the low allergenic properties of the apple cultivars
      Santana and Elise.
AB  - Patients with Oral Allergy Syndrome (OAS) to fresh apple may tolerate low
      allergenic apple cultivars. We aimed to investigate if the low allergenic
      properties of Elise and Santana, as previously identified in a Dutch population,
      could be generalised within North West Europe within the birch pollen region with
      regard to both the prevalence and degree of sensitization. Prick-to-prick tests
      (PTP) were performed in eighty-five adult patients with OAS to fresh apple in
      Great Britain, Switzerland and Northern Italy, before the birch pollen season,
      using the putatively low allergenic apple cultivars Elise, Santana, Granny Smith,
      Modi and Mcintosh, as well as the putatively high allergenic apple cultivars
      Golden Delicious and Kanzi. No significant differences in percentages of negative
      responses of PTPs were found between the three countries. Negative responses did
      not differ from negative responses to the different apple cultivars we previously
      found in 2006/2007 in the Netherlands. The size of the PTPs of all apple
      cultivars tested were correlated to the size of the skin prick tests with birch
      pollen. These results add to the indications for the low allergenic properties of
      the low allergenic apple cultivars Santana and Elise, as the number of negative
      responses were reproducible in three countries within the birch pollen region and
      were similar to previous results in the Netherlands. These results justify oral
      challenge studies with Elise and Santana within the birch pollen region, to
      establish the low allergenic properties for the benefit for apple allergic
      consumers for definite conclusions. 

PMID- 24036617
TI  - Mental health court and assisted outpatient treatment: perceived coercion,
      procedural justice, and program impact.
AB  - OBJECTIVE: Mandated community treatment has been proposed as a mechanism to
      engage people with severe and persistent mental disorders in treatment. Recently,
      two approaches to mandate treatment through the courts have been highlighted:
      assisted outpatient treatment (AOT) and mental health court programs. This study
      examined levels of perceived coercion, procedural justice, and the impact of the
      program (mental health court or AOT) among participants in a community treatment
      system. METHODS: Data were analyzed from interviews with former AOT participants
      who were no longer under court supervision (N=17) and with graduates of a mental
      health court program (N=35). The MacArthur Admission Experience Survey, created
      to measure perceived coercion, procedural justice, and program impact on hospital
      admission, was modified to include judges and case managers. RESULTS: Mental
      health court graduates perceived significantly less coercion and more procedural
      justice in their interactions with the judge than did AOT participants. No
      significant difference was found between mental health court and AOT participants
      in perceptions of procedural justice in interactions with their case managers.
      Mental health court participants felt more respected and had more positive
      feelings about the program than did AOT participants. CONCLUSIONS: Both mental
      health courts and AOT programs have potentially coercive aspects. Findings
      suggest that judges and case managers can affect participants' perceptions of
      these programs by the degree to which they demonstrate procedural justice, a
      process that may affect the long-term effects of the programs on individuals.

PMID- 24036618
TI  - Advanced glycation end products and arterial stiffness in patients with diabetic
      nephropathy and patients with chronic kidney disease without diabetes.
AB  - INTRODUCTION:  Formation of advanced glycation end-products (AGEs) is increased
      in diabetic patients. Impaired renal function also elevates AGE accumulation.
      Pulse wave velocity (PWV) is a measure of arterial stiffness and a prognostic
      parameter. An association between AGEs and arterial stiffness was observed in
      hemodialyzed patients. OBJECTIVES:  We investigated the relationship between
      plasma AGE concentration and arterial stiffness in nondialyzed patients with
      diabetic nephropathy and those with chronic kidney disease (CKD) without
      diabetes. PATIENTS AND METHODS:  PWV measurement was performed in 24 patients
      with CKD and diabetic nephropathy (DN), 36 patients with CKD and without
      diabetes, and 19 controls. To assess AGE concentrations, plasma fluorescence
      spectra were recorded.  RESULTS:  Patients with and without diabetes did not
      differ with respect to the glomerular filtration rate (33 +/-13 vs. 32 +/-14
      ml/min/1.73 m2, respectively). The AGE concentration was significantly higher in
      patients with DN compared with those without diabetes and controls (21.1 +/-6.8
      vs. 12.3 +/-3.1 vs. 7.8 +/-1.2 AU/ml, respectively; P <0.001). PWV was also
      significantly higher in patients with DN compared with those without diabetes and
      controls (13.7 +/-4.3 vs. 10.1 +/-2.4 vs. 8.4 +/-1.6 m/s, respectively; P <0.05).
      A significant correlation was found between AGEs and PWV (r = 0.39, P <0.01) in
      patients with CKD. In a multiple regression analysis, PWV was independently
      associated with age, DN, and systolic blood pressure, but not with AGEs (R2 =
      0.45).  CONCLUSIONS:  Accumulation of AGEs and arterial stiffness are increased
      in patients with CKD, particularly in those with DN; however, the results are not
      sufficient to confirm the causal role of AGE accumulation in arterial stiffening
      in CKD. AGEs should be considered as a potential therapeutic target in patients
      with CKD.

PMID- 24036619
TI  - [Change of a peripheral venous catheter: Routinely or clinically indicated].

PMID- 24036621
TI  - Researches regarding the Morton ether inhaler at Massachusetts General Hospital,
      Boston.
AB  - The Morton ether inhaler in the possession of Massachusetts General Hospital,
      Boston, MA, was traced back to 1906 when the earliest known photograph of it was
      published. The authors believe that the inhaler was given by William T. G.
      Morton, MD, to J. Mason Warren, MD, in January 1847. The inhaler was acquired by
      the Warren Anatomical Museum at an unknown date, loaned to Massachusetts General
      Hospital in October 1946, and placed on permanent loan to Massachusetts General
      Hospital in April 1948. Many documents relating to the inhaler have disappeared,
      and it was only identified in 2009 as the inhaler that probably belonged to J.
      Mason Warren, MD. The inhaler is not believed to be the one that Morton used on
      October 16, 1846, at Massachusetts General Hospital. It is the only known example
      of a Morton ether inhaler with valves (excluding replicas or reproduction
      inhalers) and is probably of similar design to the inhaler that Morton used on
      October 16, 1846. 

PMID- 24036620
TI  - How to improve the performance of intraoperative risk models: an example with
      vital signs using the surgical apgar score.
AB  - BACKGROUND: Computerized reviews of patient data promise to improve patient care
      through early and accurate identification of at-risk and well patients. The
      significance of sampling strategy for patient vital signs data is not known. In
      the instance of the surgical Apgar score (SAS), we hypothesized that larger
      sampling intervals would improve the specificity and overall predictive ability
      of this tool. METHODS: We used electronic intraoperative data from general and
      vascular surgical patients in a single-institution registry of the American
      College of Surgeons National Surgical Quality Improvement Program. The SAS,
      consisting of lowest heart rate, lowest mean arterial blood pressure, and
      estimated blood loss between incision and skin closure, was calculated using 5
      methods: instantaneously and using intervals of of 5 and 10 minutes with and
      without interval overlap. Major complications including death were assessed at 30
      days postoperatively. RESULTS: Among 3000 patients, 272 (9.1%) experienced major
      complications or death. As the sampling interval increased from instantaneous
      (shortest) to 10 minutes without overlap (largest), the sensitivity, positive
      predictive value, and negative predictive value did not change significantly, but
      significant improvements were noted for specificity (79.5% to 82.9% across
      methods, P for trend <0.001) and accuracy (76.0% to 79.3% across methods, P for
      trend <0.01). In multivariate modeling, the predictive utility of the SAS as
      measured by the c-statistic nearly increased from Deltac = +0.012 (P = 0.038) to
      Deltac = +0.021 (P < 0.002) between the shortest and largest sampling intervals,
      respectively. Compared with a preoperative risk model, the net reclassification
      improvement and integrated discrimination improvement for the shortest versus
      largest sampling intervals of the SAS were net reclassification improvement 0.01
      (P = 0.8) vs 0.06 (P = 0.02), and for integrated discrimination improvement, they
      were 0.008 (P < 0.01) vs 0.015 (P < 0.001). CONCLUSIONS: When vital signs data
      are recorded in compliance with American Society of Anesthesiologists' standards,
      the sampling strategy for vital signs significantly influences performance of the
      SAS. Computerized reviews of patient data are subject to the choice of sampling
      methods for vital signs and may have the potential to be optimized for safe,
      efficient patient care.

PMID- 24036622
TI  - Efficient catalysts of zeolite nanocrystals grown with a preferred orientation on
      nanofibers.
AB  - An innovative structure-nanozeolites (as shell) grown with preferred orientation
      on ceramic nanofibers (as core)-was proposed. The Y-zeolite nanocrystals on TiO2
      nanofibers exhibited superior ability to catalyze acetalization and carboxylation
      reactions, achieving high conversions to desired products with a selectivity of
      100% under moderate conditions. 

PMID- 24036623
TI  - Left ventricular performance after aortic valve replacement in patients with low
      ejection fraction.
AB  - The operative validity of aortic valve replacement (AVR) for high-risk patients
      with impaired left ventricular (LV) function is controversial. We measured LV
      contractility, afterload, and efficiency by use of transthoracic echocardiography
      data obtained before, after, and approximately 1 year after isolated AVR for 335
      patients with aortic stenosis (AS group; n = 160), aortic regurgitation (AR
      group; n = 116), or aortic stenosis and regurgitation (ASR group; n = 59). Two
      subgroups were created: LV ejection fraction (EF) of >=50 % (normal-EF subgroup)
      and <50 % (low-EF subgroup). Contractility decreased after AVR in the normal-EF
      AS and normal-EF AR subgroups, but did not change after AVR in the low-EF
      subgroups. Afterload decreased after AVR in the AS group and increased in the AR
      group. LV efficiency was unchanged after AVR in the normal-EF AS and ASR
      subgroups, worsened in the normal-EF AR subgroup, improved in the low-EF AS and
      ASR subgroups, and did not improve in the low-EF AR subgroup. LV contractility
      and efficiency improved during the 1-year period after AVR for all patients and
      subgroups, but the improvements in the low-EF AR subgroup were not as good as
      those in the low-EF AS and ASR subgroups. Improvements in LV contractility and
      efficiency after AVR can be expected for patients with low EF. However,
      contractility and efficiency did not improve after AVR for patients with AR and
      low EF. Low mortality and morbidity of AVR likely conceal a latent problem among
      patients with AR. 

PMID- 24036624
TI  - The effective encapsulation of a hydrophobic lipid-insoluble drug in solid lipid
      nanoparticles using a modified double emulsion solvent evaporation method.
AB  - Raloxifene HCl (RH), a selective estrogen receptor modulator (SERM), is indicated
      for the prophylaxis or treatment of postmenopausal osteoporosis. RH shows
      extremely poor bioavailability due to limited solubility and an extensive
      intestinal/hepatic first-pass metabolism. Solid lipid nanoparticles (SLNs) are
      valuable carriers that can enhance drug bioavailability. However, in the case of
      RH, the encapsulation of the drug in SLNs remains a challenge because of its poor
      solubility in both water and lipids. In this study, a series of RH-containing
      SLNs (RH-SLNs) were generated using a modified double emulsion solvent
      evaporation (DESE) method. Briefly, RH with various drug/lipid ratios was
      solubilized in the inner core of a double emulsion using different water/organic
      solvent mixtures. Our best formulation was achieved with the formation of
      negatively charged nanoparticles, 180nm in diameter, with an encapsulation and
      loading efficiency of 85% and 4.5%, respectively. It also showed a Fickian
      mechanism of the drug release in the basic dissolution media. Thermal analysis
      revealed a distinct decrease in the crystallinity of lipids and RH in comparison
      with the unprocessed materials. The results of a cell viability assay also showed
      a better antiproliferative effect of the drug-loaded SLNs versus the free drug
      solution. Thus, these results indicated that the modified DESE method could be
      proposed for the effective encapsulation of RH in SLNs with appropriate
      physicochemical and biological properties. 

PMID- 24036625
TI  - Effect of end group modification of DNA-functionalized gold nanoparticles on
      cellular uptake in HepG2 cells.
AB  - Understanding the dynamics of the cellular uptake of nanoparticles in human
      derived (cancer) cells is crucial to the rational design of functional nanoprobes
      that can be used for the targeting and delivery of drugs. This study reports on
      the cellular uptake of gold nanoparticles (GNPs) that were functionalized with
      different oligonucleotide derivatives using HepG2 cancer cells as a model system.
      DNA oligomers, in which the end group was modified (NH3, PO3, OH, CH3, and SH
      groups) were introduced onto the GNP surface. Then, quantitative and qualitative
      analyses using each DNA-GNP complex were carried out via dark-field scattering
      microscopy and ICP-MS measurements. Visualization of microscopic images of single
      cells indicated that the uptake of DNA-GNPs was highly dependent on the type of
      functionality of the end group in the DNA-GNP complex; the functionality of CH3,
      and SH resulted in less cellular uptake than that for modifications with NH3,
      PO3, OH for the same incubation time. This result was reinforced by ICP-MS
      quantitative analysis. These results were also strongly supported by the events
      of a DNA-GNP/protein corona; the different association and dissociation rates of
      proteins around the GNPs was dependent on the functionality of the end group in
      the DNA-GNP complex, providing further evidence for the conclusion that the
      components on the surface of nanoparticles directly affected cellular uptake. The
      findings reported herein provide a basis for the understanding of the fate of GNP
      based delivery and provide important insights into the rational design of
      nanoprobes for the effective treatment of various diseases. 

PMID- 24036626
TI  - Nanoassemblies containing a fluorouracil/zidovudine glyceryl prodrug with
      phospholipase A2-triggered drug release for cancer treatment.
AB  - Secretory phospholipase A2 (sPLA2), which is overexpressed in many tumors,
      cleaves ester bonds at the sn-2 position of phospholipids. A PLA2-sensitive
      amphiphilic prodrug, 1-O-octadecyl-2-(5-fluorouracil)-N-acetyl-3-zidovudine
      phosphorylglycerol (OFZG), was synthesized and used to prepare nanoassemblies
      through the injection of a mixture of OFZG/cholesterol/Tween 80 (2:1:0.1,
      mol:mol:mol) into water. Cholesterol and Tween 80 was incorporated into the OFZG
      monolayers at the air/water interface to yield nanoassemblies. The resulting
      nanoassemblies exhibited a narrow size distribution with a mean size of 77.8nm
      and were stable due to their high surface charges. The in vitro experiments
      showed that PLA2 degraded OFZG. The nanoassemblies exhibited higher anticancer
      activity than the parent drug 5-fluorouracil (5-FU) in COLO205, HT-28, and HCT
      116 cells. The intravenous (i.v.) administration of the nanoassemblies into mice
      resulted in the rapid elimination of OFZG from the circulation and its
      distribution mainly in the liver, lung, spleen, and kidney. After their injection
      into tumor-bearing mice, the nanoassemblies exhibited anticancer efficiency
      comparable to that of 5-FU, even though the nanoassemblies contained
      concentrations of only 1/10 of the molar amount of 5-FU. The lessons learned from
      the study and methods for the design of PLA2-sensitive amphiphilic prodrugs are
      also discussed. Enzyme-sensitive amphiphilic combinatorial prodrugs and prodrug
      loaded nanoassemblies may represent a new strategy for anticancer drug design. 

PMID- 24036627
TI  - Importance of extracellular proteins in maintaining structural integrity of
      aerobic granules.
AB  - Aerobic granules developed through self-immobilization of microorganisms are
      compact and structured microbial consortia embedded in a matrix of extracellular
      polymeric substances (EPS). This study investigated the contribution of
      extracellular proteins (PN) to maintaining the structural integrity of aerobic
      granule. It was found that hydrolysis of PN induced by Proteinase K led to
      significant disintegration of aerobic granules, whereas a substantial reduction
      of extracellular polysaccharides (PS) was also observed. It was proposed that
      hydrolysis of extracellular proteins present in the EPS matrix of aerobic
      granules led to collapse of the EPS matrix, and subsequent disintegration of
      aerobic granule. These suggested that extracellular proteins would be essential
      for maintaining structural stability of EPS matrix of aerobic granules. In
      addition, it was revealed that production of signaling molecules, such as
      autoinducer-2 (AI-2) and N-acyl homoserine lactones (AHLs) was also inhibited
      probably due to hydrolysis of quorum sensing receptor proteins by Proteinase K.
      This in turn provided an additional explanation for the observed Proteinase K
      triggered dispersal of aerobic granules. 

PMID- 24036628
TI  - Precisely aligned graphene grown on hexagonal boron nitride by catalyst free
      chemical vapor deposition.
AB  - To grow precisely aligned graphene on h-BN without metal catalyst is extremely
      important, which allows for intriguing physical properties and devices of
      graphene/h-BN hetero-structure to be studied in a controllable manner. In this
      report, such hetero-structures were fabricated and investigated by atomic
      resolution scanning probe microscopy. Moire patterns are observed and the
      sensitivity of moire interferometry proves that the graphene grains can align
      precisely with the underlying h-BN lattice within an error of less than 0.05
      degrees . The occurrence of moire pattern clearly indicates that the graphene
      locks into h-BN via van der Waals epitaxy with its interfacial stress greatly
      released. It is worthy to note that the edges of the graphene grains are
      primarily oriented along the armchair direction. The field effect mobility in
      such graphene flakes exceeds 20,000 cm(2).V(-1).s(-1) at ambient condition. This
      work opens the door of atomic engineering of graphene on h-BN, and sheds light on
      fundamental research as well as electronic applications based on graphene/h-BN
      hetero-structure.

PMID- 24036629
TI  - Modeling fire susceptibility to delineate wildland-urban interface for municipal
      scale fire risk management.
AB  - The wildland-urban interface (WUI) is the region where development meets and
      intermingles with wildlands. The WUI has an elevated fire risk due to the
      proximity of development and residents to wildlands with natural wildfire
      regimes. Existing methods of delineating WUI are typically applied over a large
      region, use proxies for risk, and do not consider site-specific fire hazard
      drivers. While these models are appropriate for federal and provincial risk
      management, municipal managers require models intended for smaller regions. The
      model developed here uses the Burn-P3 fire behavior model to model WUI from local
      fire susceptibility (FS) in two study communities. Forest fuel code (FFC) maps
      for the study communities were modified using remote sensing data to produce
      detailed forest edges, including ladder fuels, update data currency, and add
      buildings and roads. The modified FFC maps used in Burn-P3 produced bimodal FS
      distributions for each community. The WUI in these communities was delineated as
      areas within community bounds where FS was greater than or equal to -1 SD from
      the mean FS value ([Formula: see text]), which fell in the trough of the bimodal
      distribution. The WUI so delineated conformed to the definition of WUI. This
      model extends WUI modeling for broader risk management initiatives for municipal
      management of risk, as it (a) considers site-specific drivers of fire behavior;
      (b) models risk, represented by WUI, specific to a community; and, (c) does not
      use proxies for risk.

PMID- 24036630
TI  - Advection shapes Southern Ocean microbial assemblages independent of distance and
      environment effects.
AB  - Although environmental selection and spatial separation have been shown to shape
      the distribution and abundance of marine microorganisms, the effects of advection
      (physical transport) have not been directly tested. Here we examine 25 samples
      covering all major water masses of the Southern Ocean to determine the effects of
      advection on microbial biogeography. Even when environmental factors and spatial
      separation are controlled for, there is a positive correlation between advection
      distance and taxonomic dissimilarity, indicating that an 'advection effect' has a
      role in shaping marine microbial community composition. This effect is likely due
      to the advection of cells increasing the probability that upstream microorganisms
      will colonize downstream sites. Our study shows that in addition to distance and
      environmental selection, advection shapes the composition of marine microbial
      communities. 

PMID- 24036631
TI  - Genetic background modifies the effects of type 2 cannabinoid receptor deficiency
      on bone mass and bone turnover.
AB  - Cannabinoid receptors and their ligands play significant roles in regulating bone
      metabolism. Previous studies of type 1 cannabinoid receptor-deficient mice have
      shown that genetic background influences the skeletal phenotype. Here, we
      investigated the effects of genetic background on the skeletal phenotype of mice
      with type 2 cannabinoid receptor deficiency (Cnr2 (-/-)). We studied Cnr2 (-/-)
      mice on a CD1 background and compared the findings with those previously reported
      in Cnr2 (-/-) C57BL/6 mice. Young female Cnr2 (-/-) CD1 mice had low bone
      turnover and high trabecular bone mass compared with wild-type (WT), contrasting
      with the situation in Cnr2 (-/-) C57BL/6 mice where trabecular bone mass has been
      reported to be similar to WT. The Cnr2 (-/-) CD1 mice lost more trabecular bone
      at the tibia with age than WT due to reduced bone formation, and at 12 months
      there was no difference in trabecular bone volume between genotypes. This differs
      from the phenotype previously reported in C57BL/6 Cnr2 (-/-) mice, where bone
      turnover is increased and bone mass reduced with age. There were no substantial
      differences in skeletal phenotype between Cnr2 (-/-) and WT in male mice.
      Cortical bone phenotype was similar in Cnr2 (-/-) and WT mice of both genders.
      Deficiency of Cnr2 has site- and gender-specific effects on the skeleton, mainly
      affecting trabecular bone, which are influenced by genetic differences between
      mouse strains. Further evaluation of the pathways responsible might yield new
      insights into the mechanisms by which cannabinoid receptors regulate bone
      metabolism.

PMID- 24036632
TI  - A modular total synthesis of (+/-)-trigonoliimine C.
AB  - A convergent total synthesis of trigonoliimine C has been executed by employing
      three catalytic transformations in sequence. The key reactions that have been
      developed in this context include the [Au]-catalyzed addition of protected
      tryptamine to isatogens and the reduction of N-OH to NH with hydrazine
      monohydrate. 

PMID- 24036633
TI  - Multi-pyridine decorated Fe(II) and Ru(II) complexes by Pd(0)-catalysed cross
      couplings: new building blocks for metallosupramolecular assemblies.
AB  - Eight metal complexes of the type [M(tpy)2](2+) (tpy = 2,2':6',2''-terpyridine)
      featuring four pendant pyridine rings are reported and characterised by NMR, MS,
      absorption spectroscopy and electrochemical methods. Palladium-mediated Suzuki
      and Sonogashira cross-coupling reactions were performed on both free 4'-(3,5
      dibromophenyl)-tpy and its Ru(II) complex in good yields. The ready N-alkylation
      of the pendant pyridyl units has significant influence on the absorption and
      electrochemical reduction of the complexes, processes which are localised on the
      periphery and leaves the [Ru(tpy)2](2+) core essentially unaffected. The binding
      of metal ions by the free pyridines is also demonstrated as means of assembling
      larger ordered non-covalent structures.

PMID- 24036634
TI  - Psychometric evaluation of the hepatitis C virus patient-reported outcomes (HCV
      PRO) instrument: validity, responsiveness, and identification of the minimally
      important difference in a phase 2 clinical trial.
AB  - PURPOSE: To describe the psychometric properties and identify the minimally
      important difference (MID) of the hepatitis C virus patient-reported outcomes
      (HCV-PRO) instrument. Chronic HCV infection and associated treatments negatively
      affect PROs of function and well-being. METHODS: In a phase 2 trial, HCV-infected
      patients received direct-acting antivirals (DAAs) for 12 weeks with peg
      interferon/ribavirin (peg-IFN/RBV) for 48 weeks, or placebo plus peg-IFN/RBV. The
      HCV-PRO total score, SF-36 PCS and MCS scores, EQ-5D-3L, and EQ VAS were measured
      at baseline, week 8, end of DAA treatment (EODT), end of peg-IFN/RBV treatment
      (EOT), and posttreatment week 24 (SVR24). Convergent validity of the HCV-PRO was
      assessed by Pearson's correlation coefficients. Discriminant validity was
      assessed by analyzing mean HCV-PRO total scores by EQ-5D anxiety/depression and
      pain/discomfort domain scores (none vs. some) and presence/absence of depression
      or fatigue adverse events. MID was identified through effect size (ES) and
      receiver-operating characteristic (ROC) curve analyses (HCV-PRO response vs. SF
      36 PCS/MCS and EQ VAS MID thresholds). RESULTS: In 74 patients (22 % female; 81 %
      White; 51 % >=50 years), correlations (0.64-0.96) between HCV-PRO total scores,
      SF-36 PCS/MCS scores, and EQ VAS scores at all time points supported convergent
      validity. HCV-PRO total scores were reduced to 10-30 points in patients impaired
      by depression, pain, or fatigue symptoms. Impact of peg-IFN/RBV regimen on HCV
      PRO ES increased over time (EODT -0.76; EOT -0.93). ES and ROC curve analyses
      indicated an MID of -10 points. CONCLUSION: The HCV-PRO was valid and responsive
      in the population studied. An MID of -10 points represented a threshold of
      clinical significance for the HCV-PRO.

PMID- 24036635
TI  - Reliability of exclusively NOESY-based automated resonance assignment and
      structure determination of proteins.
AB  - Protein structure determination by NMR can in principle be speeded up both by
      reducing the measurement time on the NMR spectrometer and by a more efficient
      analysis of the spectra. Here we study the reliability of protein structure
      determination based on a single type of spectra, namely nuclear Overhauser effect
      spectroscopy (NOESY), using a fully automated procedure for the sequence-specific
      resonance assignment with the recently introduced FLYA algorithm, followed by
      combined automated NOE distance restraint assignment and structure calculation
      with CYANA. This NOESY-FLYA method was applied to eight proteins with 63-160
      residues for which resonance assignments and solution structures had previously
      been determined by the Northeast Structural Genomics Consortium (NESG), and
      unrefined and refined NOESY data sets have been made available for the Critical
      Assessment of Automated Structure Determination of Proteins by NMR project. Using
      only peak lists from three-dimensional (13)C- or (15)N-resolved NOESY spectra as
      input, the FLYA algorithm yielded for the eight proteins 91-98 % correct backbone
      and side-chain assignments if manually refined peak lists are used, and 64-96 %
      correct assignments based on raw peak lists. Subsequent structure calculations
      with CYANA then produced structures with root-mean-square deviation (RMSD) values
      to the manually determined reference structures of 0.8-2.0 A if refined peak
      lists are used. With raw peak lists, calculations for 4 proteins converged
      resulting in RMSDs to the reference structure of 0.8-2.8 A, whereas no
      convergence was obtained for the four other proteins (two of which did already
      not converge with the correct manual resonance assignments given as input). These
      results show that, given high-quality experimental NOESY peak lists, the chemical
      shift assignments can be uncovered, without any recourse to traditional through
      bond type assignment experiments, to an extent that is sufficient for calculating
      accurate three-dimensional structures.

PMID- 24036636
TI  - IAP-BLS: The golden jubilee year initiative.

PMID- 24036637
TI  - Hypertonic saline in acute bronchiolitis, is it worth the salt?

PMID- 24036638
TI  - Position of central venous catheters in children.

PMID- 24036639
TI  - Anticonvulsants for neonates: high time we were seized of the matter.

PMID- 24036640
TI  - Infantile onset diabetes mellitus.

PMID- 24036641
TI  - Adverse event following immunization (AEFI) surveillance in India, position paper
      of Indian Academy of Pediatrics,2013.
AB  - Adverse event following immunization (AEFI) is a critical component of
      immunization program. The risk of AEFI with vaccination is always weighed against
      the risk of not immunizing a child. There is an evolving AEFI surveillance system
      in India for the vaccines delivered through universal immunization program (UIP)
      of government sector, but the reporting remained suboptimal for long in the
      country, and there is almost no participation from private sector. The AEFI
      reporting from private sector will provide vital information on the safety of new
      and underutilized vaccines, not part of the UIP in India. The national guidelines
      are recently revised and updated. The Indian Academy of Pediatrics believes that
      pediatricians, especially in private sector have a crucial role to play with
      reporting of AEFI with newer/underutilized vaccines. Programmatic error, vaccine
      reaction, injection reactions, coincidental and unknown are the five broad
      categories of AEFI for programmatic purposes. The serious AEFIs (death,
      disability, cluster and hospitalization) need to be reported immediately and
      investigated in detail as per the laid down procedures. Once a serious AEFI
      happens, primary or urban health centre should be immediately informed by the
      pediatricians practicing in rural or urban areas, respectively. This advocacy
      paper from the academy provides guidelines to practitioners on how to report
      cases, and suggests ways for IAP members to help in ongoing efforts of the
      government in improving AEFI surveillance in the country. The details about the
      diagnosis and management of known/expected AEFI with UIP and newer vaccines shall
      be published later. 

PMID- 24036642
TI  - Early developmental care interventions of preterm very low birth weight infants.
AB  - The preterm very low birth weight infants are at high risk of developing
      neurodevelopmental delay despite little or no medical complications at the time
      of birth. The care and interventions of such infants have an impact on the pre
      existing risk. The Developmental Care Interventions (DCI) are the range of
      treatment strategies aiming to alleviate the risk thereby improving neuro
      developmental outcomes. The objective of this review is to appraise the range of
      such interventions for preterm very low birth weight infants reported in the
      literature. This review will help clinicians to adopt developmental intervention
      strategy to improve the neuro-developmental outcomes of their NICU graduates. 

PMID- 24036643
TI  - Guillain-Barre syndrome with acute lymphoblastic leukemia.
AB  - Guillain-Barre syndrome (GBS) is rarely reported in children with acute
      lymphoblastic leukemia and may be difficult to differentiate from vincristine
      induced neuropathy. We report two children with acute lymphoblastic leukemia on
      induction chemotherapy who developed GBS. The diagnostic issues and potential
      pathogenic mechanisms underlying GBS in pediatric patients with ALL are
      discussed. 

PMID- 24036644
TI  - Atypical hemolytic uremic syndrome with membranoproliferative glomerulonephritis.
AB  - Atypical hemolytic uremic syndrome (aHUS) associated with membranoproliferative
      glomerulonephritis (MPGN) is an uncommon clinical presentation, especially in
      children. We report a 8-year-old-boy who presented like aHUS but the kidney
      biopsy showed MPGN type 1. 

PMID- 24036645
TI  - 3p deletion syndrome.
AB  - 3p deletion is a rare cytogenetic finding. Here we describe a 3 months old male
      with congenital malformations. His karyotype revealed 3p deletion
      46,XY,del(3)(p25-pter). The child had flexion deformity of wrist and elbow which
      has never been reported before. 

PMID- 24036646
TI  - Thoracoscopic ligation of thoracic duct for spontaneous chylothorax.
AB  - Spontaneous chylothorax, without a predisposing factor is an uncommon cause of
      pleural effusion beyond the neonatal period. We present a case of left sided
      spontaneous chylothorax in a 20-month-old boy. We report successful management of
      this difficult problem with thoracoscopic ligation of thoracic duct after a
      failed trial with conservative management. 

PMID- 24036647
TI  - Is INH waging a lonely losing battle.

PMID- 24036648
TI  - Substance abuse in urban school going adolescents in India: a growing challenge.

PMID- 24036649
TI  - Updated national guidelines for pediatric tuberculosis: concerns regarding
      neurotuberculosis.

PMID- 24036650
TI  - Updated national guidelines for pediatric tuberculosis in India, 2012: some
      unresolved issues.

PMID- 24036651
TI  - Pediatric tuberculosis.

PMID- 24036652
TI  - Tuberculosis--a quest towards objectivity.

PMID- 24036653
TI  - Sudden symmetrical skin eruptions.

PMID- 24036654
TI  - Michelin tyre baby: a rare genodermatosis.

PMID- 24036655
TI  - Subungual exostosis.

PMID- 24036656
TI  - Relative TL and OSL efficiency to protons of various dosimetric materials.
AB  - Thermoluminescence (TL) and optically stimulated luminescence (OSL) are the well
      known phenomena used for passive methods of dose measurements. TL and OSL
      detectors are frequently used in the dosimetry of cosmic radiation in space and
      of particle radiotherapy beams. However, the relative TL/OSL efficiency, which is
      defined as a ratio of the emitted light intensity per unit dose for a given
      radiation type, to the same quantity for the reference gamma radiation is not
      constant and depends on radiation type and energy. In the present work several
      types of TL and OSL dosimetric materials, including lithium fluoride (LiF),
      aluminium oxide, beryllium oxide and lithium aluminate, were tested with protons.
      The measurements were realised exploiting the 60-MeV proton beam of the AIC-144
      cyclotron in the Proton Eye Radiotherapy Facility at Institute of Nuclear Physics
      (IFJ PAN). The influence of proton energy on the relative efficiency and other
      TL/OSL characteristics of the studied detector types was presented. 

PMID- 24036657
TI  - TEPC performance for a reference standard.
AB  - A portable tissue-equivalent proportional counter (TEPC)-based system was
      developed, which will be used as a reference standard in the neutron mixed field
      for radiation protection. In this paper, microdosimetry of the TEPC system was
      studied both in neutron ((252)Cf and (241)Am-Be sources) and gamma ((137)Cs and
      (60)Co sources) reference radiation fields. The measured neutron and gamma-dose
      equivalent rates were, respectively, compared with those of the reference ambient
      dose equivalent rate H(*)(10). And the measured microdosimetric spectra were
      compared with the Monte Carlo code FLUKA simulated results. All of the
      comparisons primarily agreed well. 

PMID- 24036658
TI  - Cubane and dicubane complexes stabilised by sterically demanding m-terphenyl
      ligands.
AB  - The reaction between sterically demanding m-terphenyl lithiate complexes and
      cadmium dihalides yields unusual cubanes where changes in ligand bulk afford
      different formulations, in particular a rare heterodicubane structure. 

PMID- 24036659
TI  - Targeted cholesterol efflux.

PMID- 24036660
TI  - Predictive and prognostic significance of cytoplasmic expression of ELAV-like
      protein HuR in invasive breast cancer treated with neoadjuvant chemotherapy.
AB  - Cytoplasmic HuR is associated with reduced survival in invasive breast cancer. We
      designed this study to determine the predictive and prognostic value of HuR
      expression in women with breast cancer who underwent neoadjuvant chemotherapy
      followed by surgical resection. We immunohistochemically analyzed cytoplasmic HuR
      expression in tumor biopsy cores obtained from 139 patients with invasive breast
      cancers who received paclitaxel and anthracycline-based neoadjuvant chemotherapy.
      We evaluated the relationship of HuR expression level with pathologic complete
      response (pCR), local recurrence-free survival (LRFS), distant recurrence-free
      survival (DRFS), recurrence-free survival (RFS), and overall survival (OS).
      Cytoplasmic HuR expression was present in 60 cases (43.2 %). The expression of
      cytoplasmic HuR was significantly associated with high nuclear grade (P < 0.0001)
      and ER (P = 0.001) and PR (P = 0.005) status. Multivariate regression analysis
      further revealed that high nuclear grade (P = 0.023), negative ER status (P =
      0.043), and human epidermal growth factor receptor 2 (HER2) overexpression (P <
      0.0001), but not cytoplasmic HuR expression, were significant independent
      predictors of pCR. Interestingly, multivariate Cox analysis revealed that
      cytoplasmic HuR expression was a strong independent predictor of reduced LRFS (P
      = 0.014), DRFS (P = 0.001), RFS (P < 0.0001), and OS (P = 0.019) irrespective of
      pCR. Furthermore, the patient group with tumors showing both expression of
      cytoplasmic HuR and non-pCR had a worse prognosis in LRFS (P = 0.048), DRFS (P <
      0.0001), RFS (P < 0.0001), and OS (P = 0.001) than did other patient groups;
      patients with tumors showing negative cytoplasmic expression of HuR and pCR had
      the best prognosis in all RFS and OS. Cytoplasmic expression of HuR is an
      independent prognostic marker in breast cancer patients undergoing chemotherapy.
      Combination analyses of HuR expression and pCR, compared with pCR alone, can
      better predict clinical outcome in patients with primary breast cancer.

PMID- 24036661
TI  - Use of complementary and alternative medicine (CAM) and changes in depressive
      symptoms from 3 to 15 months after surgery for primary breast cancer: results
      from a nationwide cohort study.
AB  - Background This large population-based prospective study explored the
      associations between use of complementary and alternative medicine (CAM) and
      prevalence and changes in depressive symptoms from 3 to 15 months after surgery
      for primary breast cancer. Methods In an ongoing nationwide cohort study,
      depressive symptoms and the use of ten different types of CAM since time of
      diagnosis were assessed by questionnaire at 3 (N = 3233) and 15 months post
      surgery (N = 2833). Clinical and socio-demopraphic variables were obtained from
      the Danish Breast Cancer Cooperative Group (DBCG) and national longitudinal
      registries. Results At 3 months post-surgery, 40.2 % reported having used CAM
      since the diagnosis, and in the time from 3 to 15 months after surgery, 49.9 %
      had used CAM. Compared with non-users, CAM users experienced more depressive
      symptoms at both 3 and 15 months follow-up when adjusting for several possible
      confounders. In a fully adjusted model, including all CAM variables and adjusting
      for depressive symptoms at 3 months, use of dietary/vitamin supplements was the
      only independent, statistically significant risk factor for experiencing more
      depressive symptoms at 15 months (RM = 1.10; 95 % CI 1.02-1.19, P = 0.014).
      Conclusion Cross-sectionally, CAM use was associated with higher levels of
      depressive symptoms at both time-points. Prospectively, users of dietary or
      vitamin supplements at 3 months after surgery reported higher levels of
      depressive symptoms than non-users 1 year later. Possible explanations could be
      an increased vulnerability for depressive symptoms among women using CAM or
      adverse effects of dietary or vitamin supplements.

PMID- 24036664
TI  - Stable isotopes document resource partitioning and effects of forest disturbance
      on sympatric cheirogaleid lemurs.
AB  - The future of Madagascar's forests and their resident lemurs is precarious.
      Determining how species respond to forest fragmentation is essential for
      management efforts. We use stable isotope biogeochemistry to investigate how
      disturbance affects resource partitioning between two genera of cheirogaleid
      lemurs (Cheirogaleus and Microcebus) from three humid forest sites: continuous
      and fragmented forest at Tsinjoarivo, and selectively logged forest at
      Ranomafana. We test three hypotheses: (H1) cheirogaleids are unaffected by forest
      fragmentation, (H2) species respond individually to disturbance and may exploit
      novel resources in fragmented habitat, and (H3) species alter their behavior to
      rely on the same key resource in disturbed forest. We find significant isotopic
      differences among species and localities. Carbon data suggest that Microcebus
      feed lower in the canopy than Cheirogaleus at all three localities and that
      sympatric Cheirogaleus crossleyi and C. sibreei feed at different canopy heights
      in the fragmented forest. Microcbus have higher nitrogen isotope values than
      Cheirogaleus at all localities, indicating more faunivory. After accounting for
      baseline isotope values in plants, our results provide the most support for H3.
      We find similar isotopic variations among localities for both genera. Small
      differences in carbon among localities may reflect shifts in diet or habitat use.
      Elevated nitrogen values for cheirogaleid lemurs in fragments may reflect
      increased arthropod consumption or nutritional stress. These results suggest that
      cheirogaleids are affected by forest disturbance in Eastern Madagascar and stress
      the importance of accounting for baseline isotopic differences in plants in any
      work comparing localities.

PMID- 24036662
TI  - Associations between genetic variants in the TGF-beta signaling pathway and
      breast cancer risk among Hispanic and non-Hispanic white women.
AB  - The TGF-beta signaling pathway has a significant role in breast cancer initiation
      and promotion by regulating various cellular processes. We evaluated whether
      genetic variation in eight genes (TGF-beta1, TGF-beta2, TGF-betaR1, TGF-betaR2,
      TGF-betaR3, RUNX1, RUNX2, and RUNX3) is associated with breast cancer risk in
      women from the Breast Cancer Health Disparities Study. A total of 3,524 cases
      (1,431 non-Hispanic whites (NHW); 2,093 Hispanics/Native Americans(NA)) and 4,209
      population-based controls (1,599 NHWs; 2,610 Hispanics/NAs) were included in
      analyses. Genotypes for 47 single nucleotide polymorphisms (SNPs) were
      determined. Additionally, 104 ancestral informative markers estimated proportion
      of NA ancestry. Associations with breast cancer risk overall, by menopausal
      status, NA ancestry, and estrogen receptor (ER)/progesterone receptor tumor
      phenotype were evaluated. After adjustment for multiple comparisons, two SNPs
      were significantly associated with breast cancer risk: RUNX3 (rs906296 ORCG/GG =
      1.15 95 % CI 1.04-1.26) and TGF-beta1 (rs4803455 ORCA/AA = 0.89 95 % CI 0.81
      0.98). RUNX3 (rs906296) and TGF-betaR2 (rs3773644) were associated with risk in
      pre-menopausal women (p adj = 0.002 and 0.02, respectively) and in those with
      intermediate to high NA ancestry (p adj = 0.04 and 0.01, respectively). Self
      reported race was strongly correlated with NA ancestry (r = 0.86). There was a
      significant interaction between NA ancestry and RUNX1 (rs7279383, p adj = 0.04).
      Four RUNX SNPs were associated with increased risk of ER- tumors. Results provide
      evidence that genetic variation in TGF-beta and RUNX genes are associated with
      breast cancer risk. This is the first report of significant associations between
      genetic variants in TGF-beta and RUNX genes and breast cancer risk among women of
      NA ancestry.

PMID- 24036665
TI  - Individual consistency in exploratory behaviour and mating tactics in male
      guppies.
AB  - While behavioural plasticity is considered an adaptation to fluctuating social
      and environmental conditions, many animals also display a high level of
      individual consistency in their behaviour over time or across contexts (generally
      termed 'personality'). However, studies of animal personalities that include
      sexual behaviour, or functionally distinct but correlated traits, are relatively
      scarce. In this study, we tested for individual behavioural consistency in
      courtship and exploratory behaviour in male guppies (Poecilia reticulata) in two
      light environments (high vs. low light intensity). Based on previous work on
      guppies, we predicted that males would modify their behaviour from sneak mating
      tactics to courtship displays under low light conditions, but also that the rank
      orders of courtship effort would remain unchanged (i.e. highly sexually active
      individuals would display relatively high levels of courtship under both light
      regimes). We also tested for correlations between courtship and exploratory
      behaviour, predicting that males that had high display rates would also be more
      likely to approach a novel object. Although males showed significant consistency
      in their exploratory and mating behaviour over time (1 week), we found no
      evidence that these traits constituted a behavioural syndrome. Furthermore, in
      contrast to previous work, we found no overall effect of the light environment on
      any of the behaviours measured, although males responded to the treatment on an
      individual-level basis, as reflected by a significant individual-by-environment
      interaction. The future challenge is to investigate how individual consistency
      across different environmental contexts relates to male reproductive success.

PMID- 24036666
TI  - Preventing seclusion in psychiatry: a care ethics perspective on the first five
      minutes at admission.
AB  - In this article, an intervention aimed at improving quality of care to prevent
      seclusion in psychiatry by focusing on the first five minutes at admission is
      analyzed from a care ethics perspective. Two cases are presented from an
      evaluation study in a psychiatric hospital. In both cases, the nurses follow the
      intervention protocol, but the outcome is different. In the first case, the
      patient ends up in the seclusion room. In the second case, this does not happen.
      Analyzing the cases from a care ethics perspective, we conclude that applying the
      intervention in the right way implies more than following the steps laid down in
      the protocol. It requires a new way of thinking and acting, resulting in new
      relationships between nurses and patients. Care ethics theory can help clarify
      what good care is actually about and keep in mind what is needed to apply the
      intervention. Thus, care ethics theory can be highly practical and helpful in
      changing and improving healthcare practice. 

PMID- 24036667
TI  - Factors associated with nurses' opinions and practices regarding information and
      consent.
AB  - This cross-sectional survey aimed to investigate nurses' opinions and practices
      regarding information and consent in the context of a large Italian teaching
      hospital and to explore potential influences of gender, age, university
      education, length of professional experience, and care setting. A questionnaire
      was administered to 282 nurses from six different care settings (Emergency Room,
      Emergency Medicine, Surgery, Hematology-Oncology, Geriatrics, and Internal
      Medicine). Overall, 84% (n = 237) of nurses returned the questionnaire (men: 24%;
      mean age: 36.2 +/- 8 years; university degree: 35%; mean length of professional
      experience: 12 +/- 8.2 years). Most respondents regularly informed patients about
      medications and nursing procedures and asked for consent prior to invasive
      procedures, but some provided information to relatives instead of patients. Lack
      of time or opportunity was the main difficulty in informing patients. The work
      setting was the foremost factor significantly associated with participants'
      opinions and practices. Further investigations are needed to confirm these
      findings in similar and other care settings. 

PMID- 24036668
TI  - Iranian nurses' perceptions of social responsibility: a qualitative study.
AB  - Social responsibility is intertwined with nursing; however, perceptions of
      Iranian nurses about social responsibility has not been explored yet. This study,
      as part of a larger qualitative grounded theory approach study, aims to explore
      Iranian nurses' perception of social responsibility. The study participants
      included 10 nurses with different job levels. The study data were generated
      through semi-structured interviews. The participants were selected through
      purposeful sampling approach, which was then followed by theoretical sampling
      until reaching the point of data saturation. All the interviews were recorded,
      transcribed, and analyzed through constant comparative analysis. Positive human
      characteristics, professional competencies, professional values, solution-focused
      nursing care, and deployment of professional performance are five categories
      obtained from the study. The participants believed socially responsible nurses to
      have positive personality characteristics as well as the necessary skills to do
      their duties accurately. Such nurses also respect the values, observe the
      professional principles, and take major steps toward promotion and deployment of
      the nursing profession in the society. 

PMID- 24036669
TI  - Proteolytic activation of Chlamydia trachomatis HTRA is mediated by PDZ1 domain
      interactions with protease domain loops L3 and LC and beta strand beta5.
AB  - Chlamydia trachomatis is a bacterial pathogen responsible for one of the most
      prevalent sexually transmitted infections worldwide. Its unique development cycle
      has limited our understanding of its pathogenic mechanisms. However, CtHtrA has
      recently been identified as a potential C. trachomatis virulence factor. CtHtrA
      is a tightly regulated quality control protein with a monomeric structural unit
      comprised of a chymotrypsin-like protease domain and two PDZ domains. Activation
      of proteolytic activity relies on the C-terminus of the substrate allosterically
      binding to the PDZ1 domain, which triggers subsequent conformational change and
      oligomerization of the protein into 24-mers enabling proteolysis. This activation
      is mediated by a cascade of precise structural arrangements, but the specific
      CtHtrA residues and structural elements required to facilitate activation are
      unknown. Using in vitro analysis guided by homology modeling, we show that the
      mutation of residues Arg362 and Arg224, predicted to disrupt the interaction
      between the CtHtrA PDZ1 domain and loop L3, and between loop L3 and loop LD,
      respectively, are critical for the activation of proteolytic activity. We also
      demonstrate that mutation to residues Arg299 and Lys160, predicted to disrupt
      PDZ1 domain interactions with protease loop LC and strand beta5, are also able to
      influence proteolysis, implying their involvement in the CtHtrA mechanism of
      activation. This is the first investigation of protease loop LC and strand beta5
      with respect to their potential interactions with the PDZ1 domain. Given their
      high level of conservation in bacterial HtrA, these structural elements may be
      equally significant in the activation mechanism of DegP and other HtrA family
      members. 

PMID- 24036670
TI  - Light and competition gradients fail to explain the coexistence of shade-tolerant
      Fagus sylvatica and shade-intermediate Quercus petraea seedlings.
AB  - BACKGROUND AND AIMS: The coexistence of forest tree species has often been linked
      to differences among species in terms of their response to light availability
      during the regeneration stage. From this perspective, species coexistence results
      from growth-growth or mortality-growth trade-offs along spatial light gradients.
      Experimental evidence of growth-growth trade-offs in natural conditions is sparse
      due to various confounding factors that potentially hinder the relationship. This
      study examined growth hierarchies along light gradients between two tree species
      with contrasting shade tolerance by controlling potential confounding factors
      such as seedling size, seedling status, seedling density and species composition.
      METHODS: Natural regenerated shade-tolerant Fagus sylvatica and shade
      intermediate Quercus petraea seedlings were used, and growth rankings over a 4
      year period were compared in 8- to 10-year-old tree seedlings. KEY RESULTS: No
      rank reversal occurs between the two species along the light gradient, or along
      the density, mixture or seedling size gradients. The shade-tolerant species was
      always the more competitive of the two. Pronounced effects of initial size on
      seedling growth were observed, whereas the effects of light and competition by
      neighbours were of secondary importance. The paramount effect of size, which
      results from the asymmetric nature of interseedling competition, gives a strong
      advantage to tall seedlings over the long term. CONCLUSIONS: This study extends
      previous efforts to identify potential drivers of rank reversals in young tree
      mixtures. It does not support the classical assumption that spatial heterogeneity
      in canopy opening explains the coexistence of the two species studied. It
      suggests that spatial variation in local size hierarchies among seedlings that
      may be caused by seedling emergence time or seedling initial performance is the
      main driver of the dynamics of these mixed stands.

PMID- 24036671
TI  - Ivy sign, misery perfusion, and asymptomatic moyamoya disease: FLAIR imaging and
      (15)O-gas positron emission tomography.
AB  - BACKGROUND: The prevalence of ivy sign on fluid-attenuated inversion recovery
      (FLAIR) imaging in patients with asymptomatic moyamoya disease is unclear. The
      aim of this study was to clarify the incidence of ivy sign in these patients, as
      well as the correlation between MRI and (15)O gas PET findings. METHODS: A
      retrospective analysis including 16 consecutive patients with asymptomatic
      moyamoya disease enrolled between 2001 and 2010 in a single center. FLAIR imaging
      at the initial visit was categorized as ivy sign present, negative, or equivocal.
      Hemodynamic and metabolic parameters were quantified in 11 of 16 patients by
      (15)O-gas positron emission tomography, and the relationship between ivy sign and
      (15)O-gas PET parameters was analyzed. Cerebrovascular events within the follow
      up period (54 +/- 28 months) were also examined. RESULTS: Five of 16 asymptomatic
      moyamoya patients (31.3 %) had positive ivy sign (6/30 hemispheres, 20 %). In
      (15)O-gas PET examinations, 18 % of 22 hemispheres had elevated oxygen extraction
      fraction values that were significantly associated with positive ivy sign. Of
      these 16 asymptomatic moyamoya patients, six patients (37.5 %) underwent combined
      surgical revascularization. In this series, no patients experienced ischemic
      stroke, but one had intraventricular bleeding 1 year after surgery. CONCLUSIONS:
      Ivy sign on FLAIR imaging is still not rare in patients with moyamoya disease,
      even when asymptomatic. Although optimal management is still under debate, ivy
      sign may be an indicator of misery perfusion, and patients with asymptomatic
      moyamoya disease and ivy sign on FLAIR imaging will benefit from more careful
      follow-up.

PMID- 24036672
TI  - Falcine venous plexus within the falx cerebri: anatomical and scanning electron
      microscopic findings and clinical significance.
AB  - BACKGROUND: Only limited attention has been paid to the anatomy and clinical
      importance of the falcine venous plexus. The aim of this study was to evaluate
      the falcine venous plexus anatomically using scanning electron microscopy (SEM),
      and to provide guidance for neurosurgical approaches. METHODS: Latex or ink was
      injected into the superior and inferior sagittal sinus. The falcine venous plexus
      lying within the connective tissue of the falx cerebri was observed by dividing
      the falx into thirds (anterior, middle and posterior). Further, the SEM
      appearance of the falcine venous plexus was evaluated. RESULTS: The anterior
      third of the falx cerebri consisted of small diameter falcine venous vessels.
      These vessels were localized close to either the superior or inferior sagittal
      sinus, and none extended as far as mid-falx cerebri levels in any of the 16
      cases. They communicated with either superior or inferior sagittal sinuses, but
      not with both of these sinuses. In the middle third of the falx cerebri, the
      majority of the vessels of the falcine venous plexus had larger diameter compared
      to those of the anterior third. These vessels extended the length of the falx
      cerebri levels. They communicated with both superior and inferior sagittal
      sinuses. In the posterior third of the falx cerebri, the vessels of the falcine
      venous plexuses had the largest diameter and were located at the junction of the
      inferior sagittal sinus and the straight sinus. They were localized at the lower
      two-thirds of the falx cerebri. In all cases, the dense venous networks
      communicated with the inferior sagittal sinus but not with the superior sagittal
      sinus. The falcine venous plexus observed in the posterior third of the falx
      cerebri was denser than in the anterior and middle portions. The SEM revealed
      small vessels whose diameter ranged between 42 and 138 MUm. The vessels of the
      falcine venous plexus in the anterior third had a mean diameter of 0.42 +/- 0.1
      mm, in the middle third a mean diameter of 0.87 +/- 0.17 mm, and in the posterior
      third, 1.38 +/- 0.21 mm. CONCLUSION: The falcine venous plexus is a network of
      venous channels that exists within the connective tissue of the falx; the sizes
      and patterns of communication of these structures showed regional differences.
      Neurosurgeons should be aware of the regional differences when making an incision
      or puncturing the falx during a surgical approach.

PMID- 24036673
TI  - Two-step tunneling technique of deep brain stimulation extension wires-a
      description.
AB  - INTRODUCTION: While a significant body of literature exists on the intracranial
      part of deep brain stimulation surgery, the equally important second part of the
      intervention related to the subcutaneous tunneling of deep brain stimulation
      extension wires is rarely described. The tunneling strategy can consist of a
      single passage of the extension wires from the frontal incision site to the
      subclavicular area, or of a two-step approach that adds a retro-auricular counter
      incision. Each technique harbors the risk of intraoperative and postoperative
      complications. METHOD: At our center, we perform a two-step tunneling procedure
      that we developed based on a cadaveric study. RESULTS: In 125 consecutive
      patients operated since 2002, we did not encounter any complication related to
      our tunneling method. CONCLUSION: Insufficient data exist to fully evaluate the
      advantages and disadvantages of each tunneling technique. It is of critical
      importance that authors detail their tunneling modus operandi and report the
      presence or absence of complications. This gathered data pool may help to
      formulate a definitive conclusions on the safest method for subcutaneous
      tunneling of extension wires in deep brain stimulation.

PMID- 24036674
TI  - Intraoperative angiography reloaded: a new hybrid operating theater for combined
      endovascular and surgical treatment of cerebral arteriovenous malformations: a
      pilot study on 25 patients.
AB  - BACKGROUND: Multimodality treatment suites for patients with cerebral
      arteriovenous malformations (AVM) have recently become available. This study was
      designed to evaluate feasibility, safety and impact on treatment of a new
      intraoperative flat-panel (FP) based integrated surgical and imaging suite for
      combined endovascular and surgical treatment of cerebral AVM. METHODS: Twenty
      five patients with AVMs to treat with combined endovascular and surgical
      interventions were prospectively enrolled in this consecutive case series. The
      hybrid suite allows combined endovascular and surgical approaches with
      intraoperative scanner-like imaging (XperCT(r)) and intraoperative 3D rotational
      angiography (3D-RA). The impact of intraoperative multimodal imaging on
      feasibility, workflow of combined interventions, surgery, and unexpected imaging
      findings were analyzed. RESULTS: Twenty-five patients (mean age 38 +/- 18.6 year)
      with a median Spetzler-Martin grade 2 AVM (range 1-4) underwent combined
      endovascular and surgical procedures. Sixteen patients presented with a ruptured
      AVM and nine with an unruptured AVM. In 16 % (n = 4) of cases, intraoperative
      imaging visualized AVM remnants <=3 mm and allowed for completion of the
      resections in the same sessions. Complete resection was confirmed in all n = 16
      patients who had follow-up angiography one year after surgery so far. All
      diagnostic and therapeutical steps, including angiographic control, were
      performed without having to move the patients CONCLUSION: The hybrid
      neurointerventional suite was shown to be a safe and useful setup which allowed
      for unconstrained combined microsurgical and neuroradiological workflow. It
      reduces the need for extraoperative angiographic controls and subsequent
      potential surgical revisions a second time, as small AVM remnants can be detected
      with high security.

PMID- 24036675
TI  - Usefulness of three-dimensional navigable intraoperative ultrasound in resection
      of brain tumors with a special emphasis on malignant gliomas.
AB  - BACKGROUND: Intraoperative imaging is increasingly being used in resection of
      brain tumors. Navigable three-dimensional (3D)-ultrasound is a novel tool for
      planning and guiding such resections. We review our experience with this system
      and analyze our initial results, especially with respect to malignant gliomas.
      METHODS: A prospective database for all patients undergoing sononavigation-guided
      surgery at our center since this surgery's introduction in June 2011 was queried
      to retrieve clinical data and technical parameters. Imaging was reviewed to
      categorize tumors based on enhancement and resectability. Extent of resection was
      also assessed. RESULTS: Ninety cases were operated and included in this analysis,
      75 % being gliomas. The 3D ultrasound mode was used in 87 % cases (alone in 40,
      and combined in 38 cases). Use of combined mode function [ultrasound (US) with
      magnetic resonance (MR) images] facilitated orientation of anatomical data.
      Intraoperative power Doppler angiography was used in one-third of the cases, and
      was extremely beneficial in delineating the vascular anatomy in real-time. Mean
      duration of surgery was 4.4 hours. Image resolution was good or moderate in about
      88 % cases. The use of the intraoperative imaging prompted further resection in
      59 % cases. In the malignant gliomas (51 cases), gross-total resection was
      achieved in 47 % cases, increasing to 88 % in the "resectable" subgroup.
      CONCLUSIONS: Navigable 3D US is a versatile, useful and reliable intraoperative
      imaging tool in resection of brain tumors, especially in resource-constrained
      settings where Intraoperative MR (IOMR) is not available. It has multiple
      functionalities that can be tailored to suit the procedure and the experience of
      the surgeon.

PMID- 24036676
TI  - Nano-scale hydrogen-bond network improves the durability of greener cements.
AB  - More than ever before, the world's increasing need for new infrastructure demands
      the construction of efficient, sustainable and durable buildings, requiring
      minimal climate-changing gas-generation in their production. Maintenance-free
      "greener" building materials made from blended cements have advantages over
      ordinary Portland cements, as they are cheaper, generate less carbon dioxide and
      are more durable. The key for the improved performance of blends (which
      substitute fine amorphous silicates for cement) is related to their resistance to
      water penetration. The mechanism of this water resistance is of great
      environmental and economical impact but is not yet understood due to the
      complexity of the cement's hydration reactions. Using neutron spectroscopy, we
      studied a blend where cement was replaced by ash from sugar cane residuals
      originating from agricultural waste. Our findings demonstrate that the
      development of a distinctive hydrogen bond network at the nano-scale is the key
      to the performance of these greener materials. 

PMID- 24036677
TI  - Genetic testing and genetic counseling among Medicaid-enrolled children with
      autism spectrum disorder in 2001 and 2007.
AB  - The rise in the prevalence of autism spectrum disorder (ASD) has resulted in
      increased efforts to understand the causes of this complex set of disorders that
      emerge early in childhood. Although research in this area is underway and
      yielding useful, but complex information about ASD, guidelines for the use of
      genetic testing and counseling among children with ASD conflict. The purpose of
      this study was to determine the frequency of use of genetic testing and
      counseling before the widespread implementation of clinical chromosomal
      microarray (CMA) to establish a baseline for the use of both services and to
      investigate potential disparities in the use of both services among children with
      ASD. We found that about two-thirds of children with ASD received genetic testing
      or counseling and the use of both services is increasing with time, even in the
      pre-CMA era. Being female and having a comorbid intellectual disability diagnosis
      both increased the likelihood of receiving genetic testing and genetic
      counseling. Initial discrepancies in the use of both services based on
      race/ethnicity suggest that troubling disparities observed in other services
      delivered to children with ASD and other mental health disorders persist in
      genetic testing and counseling as well. These results should incentivize further
      investigation of the impact of genetic testing and counseling on children with
      ASD and their families, and should drive efforts to explore and confront
      disparities in the delivery of these services, particularly with the advancing
      scientific research on this topic. 

PMID- 24036678
TI  - Health-related quality-of-life outcomes in coronary artery bypass surgery
      patients and partners.
AB  - PURPOSE: The purpose of this study was to examine health-related quality-of-life
      (HRQOL) outcomes in coronary artery bypass surgery (CABS) patients and partners
      enrolled together in cardiac rehabilitation versus a usual care group. METHODS:
      After CABS, couples were randomly assigned to the Partners Together in Health
      (PaTH) intervention (n = 17) or usual care (n = 17) groups. Health-related
      quality-of-life was operationalized as physical function (SF-36 Physical
      Functioning subscale), depression (Patient Health Questionnaire), and marital
      adjustment (Dyadic Adjustment Scale). Data were measured in patients and partners
      at the start (T1) and end of cardiac rehabilitation (T2), and 3 months after
      cardiac rehabilitation (T3). Nonparametric statistics were used to examine
      changes over time and differences between groups. RESULTS: Patients in both
      groups, and partners in the PaTH group, significantly improved physical function
      between T1 and T2. At T1, 18% of patients and 6% of partners were depressed. At
      T2 and T3, only 3% of patients and no partners were depressed. Almost 12% of
      patients and partners were maritally distressed at T1. At T2 and T3, patients'
      marital distress was unchanged, but more partners reported marital distress
      (15%). CONCLUSIONS: This study adds to our understanding of the trajectory of
      HRQOL outcomes after CABS for patients and partners. These findings demonstrated
      promise for the PaTH intervention. Future testing of the intervention is
      warranted in a larger sample. Because patients and partners are impacted by CABS
      as a shared life experience, couple-centered interventions may improve HRQOL
      outcomes more than individually focused interventions.

PMID- 24036679
TI  - Comparative morphometry of the antebrachial and crural interosseous membranes:
      preliminary study for the use of the crural interosseous membrane in the surgical
      repair of the antebrachial interosseous membrane tears.
AB  - INTRODUCTION: Traumatic tears of the antebrachial interosseous membrane (AIOM) on
      its whole length are difficult to treat, particularly in the Essex-Lopresti
      syndrome. The number of ligamentoplasty techniques described in the literature
      witnesses the difficulty of its reconstruction and the absence of reliable and
      satisfying procedure. The aim of this study was to explore a new way of
      treatment, which consists in replacing the AIOM by the crural interosseous
      membrane (CIOM), harvested from the same patient. MATERIALS AND METHODS: A
      morphometric study of the AIOM and CIOM has been conducted on both sides of 15
      formalin preserved corpses (i.e. 30 AIOM and 30 CIOM). Studied data were: length
      of forearms and legs, length and width (at different locations) of the membranes,
      in situ and after harvesting, and orientation of their fibers. The thickness of
      membrane was also measured but only after harvesting. RESULTS: Concerning the
      AIOM, the mean length was 13.3 cm in situ and 12.8 cm after harvesting. Its width
      was maximal at the union of middle and distal thirds with an average value of 1.7
      cm in situ and 1.45 cm after harvesting. Mean thickness was 1 mm. Anterior fibers
      were oblique distally and medially (20.5 degrees  +/- 0.95 degrees ), and
      posterior fibers were oblique distally and laterally (40 degrees  +/- 3.4 degrees
      ). Concerning the CIOM, the mean length was 24.75 cm in situ and 23.9 cm after
      harvesting. Its width was maximal at the union of proximal and middle thirds with
      an average value of 2.3 cm in situ and 1.85 cm after harvesting. Mean thickness
      was 0.5 mm. Obliquity of its fibers was reverse of that of the AIOM: the anterior
      fibers were quite oblique distally and laterally (13 degrees  +/- 2.6 degrees ),
      and the posterior fibers oblique were oblique distally and medially (24.2 degrees
      +/- 2.48 degrees ). DISCUSSION: From these results, one may conclude that the
      largest length and width of the CIOM allow its use as substitute for the injured
      AIOM. The orientation of its fibers should necessitate either its reversal while
      using the same side or the use of the CIOM of the opposite side; its relative
      sharpness could signify that its biomechanical properties could be worse. A
      biomechanical study is necessary to evaluate how this new way of replacing the
      AIOM could resist to the strains imposed on the forearm.

PMID- 24036680
TI  - Functions and roles of a protein-associated factor.
AB  - The divergence of protein (Hedgehog) in different organisms remains an unresolved
      issue to comprehend how the pathway in Hh signaling evolves. Insights into this
      question can help one identify the key molecules in Hh signaling. This work
      proposes a protein-associated factor in cells. The development of a non
      reductionist theory of cellular functions in medicine is not sufficient. It is
      necessary to find the parameters with regards to molecules/genes that can elicit
      functions. This work shows that molecular interactions of gene products can be
      accomplished by biophysics logic. Defining the protein-associated factors in
      molecular activities and identifying its roles in molecular transduction are
      important. A misregulation in molecular switch can account for complex
      biomolecular consequences. This work shows the potential of the factor on homo
      sapiens and unlocks its implications to gene multi-tasking functionality. The
      associated factor notion should facilitate the medical development in cancer
      therapeutics. 

PMID- 24036681
TI  - Complete stereocontrol in the synthesis of macrocyclic lanthanide complexes:
      direct formation of enantiopure systems for circularly polarised luminescence
      applications.
AB  - Mono-C-substitution of the 1,4,7-triazacyclononane ring induces formation of
      single enantiomers of Eu(III) complexes with nonadentate N6O3 ligands. The
      absolute configuration of each complex is determined by the stereogenicity of the
      C-substituent, revealed by comparison of the sign and sequence of CPL transitions
      for a series of complexes.

PMID- 24036684
TI  - Changes in biomarkers of liver disease during successful combination
      antiretroviral therapy in HIV-HCV-coinfected individuals.
AB  - BACKGROUND: We investigated changes in biomarkers of liver disease in HIV-HCV
      coinfected individuals during successful combination antiretroviral therapy
      (cART) compared to changes in biomarker levels during untreated HIV infection and
      to HIV-monoinfected individuals. METHODS: Non-invasive biomarkers of liver
      disease (hyaluronic acid [HYA], aspartate aminotransferase-to-platelet ratio
      index [APRI], Fibrosis-4 [FIB-4] index and cytokeratin-18 [CK-18]) were
      correlated with liver histology in 49 HIV-HCV-coinfected patients. Changes in
      biomarkers over time were then assessed longitudinally in HIV-HCV-coinfected
      patients during successful cART (n=58), during untreated HIV-infection (n=59),
      and in HIV-monoinfected individuals (n=17). The median follow-up time was 3.4
      years on cART. All analyses were conducted before starting HCV treatment.
      RESULTS: Non-invasive biomarkers of liver disease correlated significantly with
      the histological METAVIR stage (P<0.002 for all comparisons). The mean +/-sd area
      under the receiver operating characteristic (AUROC) curve values for advanced
      fibrosis (>=F3 METAVIR) for HYA, APRI, FIB-4 and CK-18 were 0.86 +/-0.05, 0.84 +/
      0.08, 0.80 +/-0.09 and 0.81 +/-0.07, respectively. HYA, APRI and CK-18 levels
      were higher in HIV-HCV-coinfected compared to HIV-monoinfected patients (P<0.01).
      In the first year on cART, APRI and FIB-4 scores decreased (-35% and -33%,
      respectively; P=0.1), mainly due to the reversion of HIV-induced
      thrombocytopaenia, whereas HYA and CK-18 levels remained unchanged. During long
      term cART, there were only small changes (<5%) in median biomarker levels. Median
      biomarker levels changed <3% during untreated HIV-infection. Overall, 3 patients
      died from end-stage liver disease, and 10 from other causes. CONCLUSIONS:
      Biomarkers of liver disease highly correlated with fibrosis in HIV-HCV-coinfected
      individuals and did not change significantly during successful cART. These
      findings suggest a slower than expected liver disease progression in many HIV-HCV
      coinfected individuals, at least during successful cART.

PMID- 24036685
TI  - Human gut microbiota community structures in urban and rural populations in
      Russia.
AB  - The microbial community of the human gut has a crucial role in sustaining host
      homeostasis. High-throughput DNA sequencing has delineated the structural and
      functional configurations of gut metagenomes in world populations. The microbiota
      of the Russian population is of particular interest to researchers, because
      Russia encompasses a uniquely wide range of environmental conditions and
      ethnogeographical cohorts. Here we conduct a shotgun metagenomic analysis of gut
      microbiota samples from 96 healthy Russian adult subjects, which reveals novel
      microbial community structures. The communities from several rural regions
      display similarities within each region and are dominated by the bacterial taxa
      associated with the healthy gut. Functional analysis shows that the metabolic
      pathways exhibiting differential abundance in the novel types are primarily
      associated with the trade-off between the Bacteroidetes and Firmicutes phyla. The
      specific signatures of the Russian gut microbiota are likely linked to the host
      diet, cultural habits and socioeconomic status. 

PMID- 24036687
TI  - sp3-Bonded silicon allotropes based on the Kelvin problem.
AB  - The Kelvin problem, how to partition three-dimensional space into cells of equal
      volume with minimal area, is a fascinating one. Aggregations of bubbles are
      naturally physical illustrations of the Kelvin problem. And the superconductor
      Na8Si46 as an inspiration leads to an amazing discovery of the Weaire-Phelan (WP)
      structure of foam - the optimal solution to the Kelvin problem to date. Here
      based on the structural similarity between sp(3)-bonded silicon allotropes and
      the solutions to the Kelvin problem, a series of new sp(3)-hybridization silicon
      allotropes, named "Kelvin Silicons", are presented. Furthermore, the structural
      stability and electronic properties of these new silicon allotropes are
      investigated using density-functional theory (DFT) calculations. The results show
      that Kelvin Silicons are structurally stable semiconductors with indirect
      bandgaps in the range of 0.17-1.40 eV, and their bulk moduli are about 75.9-88.5%
      that of the diamond phase. The simulated X-ray diffraction spectra of the new
      silicon crystalline structures would provide more information for possible
      experimental observations and synthesis. 

PMID- 24036686
TI  - Chromosome movement in meiosis I prophase of Caenorhabditis elegans.
AB  - Rapid chromosome movement during prophase of the first meiotic division has been
      observed in many organisms. It is generally concomitant with formation of the
      "meiotic chromosome bouquet," a special chromosome configuration in which one or
      both chromosome ends attach to the nuclear envelope and become concentrated
      within a limited area. The precise function of the chromosomal bouquet is still
      not fully understood. Chromosome mobility is implicated in homologous chromosome
      pairing, synaptonemal complex formation, recombination, and resolution of
      chromosome entanglements. The basic mechanistic module through which forces are
      exerted on chromosomes is widely conserved; however, phenotypic differences have
      been reported among various model organisms once movement is abrogated. Movements
      are transmitted to the chromosome ends by the nuclear membrane-bridging SUN/KASH
      complex and are dependent on cytoskeletal filaments and motor proteins located in
      the cytoplasm. Here we review the recent findings on chromosome mobility during
      meiosis in an animal model system: the Caenorhabditis elegans nematode. 

PMID- 24036688
TI  - Serum 25-hydroxyvitamin D predicts severity in Parkinson's disease patients.
AB  - In recent years, increasing evidence has shown that individuals with Parkinson's
      disease (PD) have lower levels of 25-hydroxyvitamin D [25(OH) D] relative to
      healthy controls. We therefore evaluated the relationship between serum 25(OH) D
      levels and severity in Chinese patients with a Parkinson's disease. From July
      2010 to June 2012, consecutive PD patients admitted to the Department of
      Neurology of General Hospital, Tianjin Medical University, were identified.
      Clinical information and disease duration were collected. Serum level of 25(OH) D
      was measured at baseline. PD severity was assessed at admission using the Hoehn
      and Yahr (HY) stage and Unified Parkinson's Disease Rating Stage (UPDRS) total
      score. The results indicated that the mean serum 25(OH) D levels were
      significantly lower in PD patients as compared to normal cases (P < 0.001). There
      was a negative correlation between levels of 25(OH) D and the disease duration [r
      (spearman) = -0.124, P = 0.041]. There was a significant negative relationship
      between circulating serum 25(OH) D levels and severity of Parkinson's disease
      evaluated by HY stage (P = 0.030) and UPDRS Stage (P = 0.000) even after
      multivariate adjustment for possible confounders: age, gender, disease duration,
      levels of Ca, ALP, blood glucose, and seasons. These results suggest that lower
      25(OH) D levels may be associated with severity of PD in Chinese patients.

PMID- 24036689
TI  - Serum glial fibrillary acidic protein as a biomarker for differentiating
      intracerebral hemorrhage and ischemic stroke in patients with symptoms of acute
      stroke: a systematic review and meta-analysis.
AB  - Serum glial fibrillary acidic protein (GFAP) has been reported to have high
      diagnosis accuracy for differentiating intracerebral hemorrhage (ICH) from
      ischemic stroke (IS) in patients within acute phase of stroke symptom onset. Our
      purpose was to perform a systematic review and diagnostic meta-analysis to
      evaluate the valuation of serum GFAP in the early identification of ICH and IS.
      We searched MEDLINE, EMBASE and other electronic databases for diagnostic
      accuracy studies that compared serum GFAP with standard clinical diagnosis of ICH
      and IS in patients with symptoms of acute stroke. All publication years were
      included through to April 2013. The sensitivity (SEN), specificity (SPE), and
      positive and negative likelihood ratios (PLR and NLR, respectively) of serum GFAP
      for differentiating ICH and IS were pooled using a bivariate meta-analysis.
      Summary receiver operating characteristic curves were used to summarize overall
      test performance. A total of five trials met our inclusion criteria. The
      summarized estimates of serum GFAP for the differentiation of ICH and IS within
      24 h of symptom onset were as follows: SEN, 81.1% (95% CI, 72.6-87.5%); SPE,
      95.2% (95% CI 82.1-98.9%); PLR, 16.945 (95% CI 4.173-68.803); NLR, 0.198 (95% CI
      0.133-0.296), significant heterogeneity was present. The four summary estimates
      of serum GFAP for patients within 1-6 h of symptom onset were 81.1% (95% CI 72.5
      88.0%), 97.0% (95% CI 94.3-98.4%), 26.786 (95% CI 13.979-51.324), 0.191 (95% CI
      0.126-0.291), respectively, with no obvious heterogeneity. Serum GFAP is a
      sensitive and specific test for differentiating ICH and IS in patients within 1-6
      h of acute stroke symptom onset.

PMID- 24036691
TI  - The effectiveness of selected Tai Chi exercises in a program of strategic
      rehabilitation aimed at improving the self-care skills of patients aroused from
      prolonged coma after severe TBI.
AB  - BACKGROUND: Difficulties in self-care constitute a very common problem for
      patients recovering from prolonged coma after a severe TBI, and a major factor
      reducing their quality of life. Effective new rehabilitation programs that would
      help solve this problem are urgently needed. The purpose of our experiment was to
      evaluate improvement in this respect in a group of patients aroused from
      prolonged coma who participated in a goal-oriented rehabilitation program (Rehab
      3), enhanced with selected elements of Tai-Chi. MATERIAL/METHODS: We examined 40
      patients aroused from prolonged coma after a severe TBI, undergoing long-term
      rehabilitation according to a standard phased rehabilitation program. These
      patients were divided into two numerically even groups: a control group treated
      according to the standard program, and an experimental group, who received an
      additional goal oriented program enhanced with selected Tai-Chi exercises. The
      research methods included analysis of documentation (MRI, CT), a structured
      clinical interview, and the Standard Self-Care Scale. RESULTS: The experimental
      group achieved significant improvement of self-care skills, whereas in the
      control group the improvement was slight and not statistically significant. The
      value of co-efficient j (0.64) indicates a very strong association between the
      rehabilitation procedure and improved self-care in the experimental group, but
      not in the control group. CONCLUSIONS: Our results confirmed that a goal-oriented
      rehabilitation program enhanced with elements of Tai-Chi was more effective than
      the standard program in improving the performance of activities of daily living.

PMID- 24036692
TI  - The effect of country wealth on incidence of breast cancer.
AB  - The aim of this study is to analyze the relationship between the incidence of
      breast cancer and income per capita across countries. Data on breast cancer
      incidence in 52 countries were obtained from GLOBOCAN, along with economic
      indicators of gross domestic product per capita from the World Bank. Number of
      computed tomography scanners and magnetic resonance imaging (from World Health
      Organization) were used as a surrogate for technology and access to screening for
      cancer diagnosis. Statistical analyses for correlation and regression were
      performed, along with an analysis of variance (ANOVA). A strong positive
      association between breast cancer incidence and gross domestic product per
      capita, Pearson's r = 65.4 %, controlling latitude, density of computed
      tomography scanners and magnetic resonance imaging was found in countries of
      temperate zones. The estimated relationship suggests that 1 % higher gross
      domestic product per capita, within the temperate zones (latitudes), increases
      the expected age-standardized breast cancer incidence by about 35.6 % (p <
      0.001). ANOVA confirms these vital results. While some have argued that latitude
      and seasonality may affect breast cancer incidence, these findings suggest that
      wealthier nations may have a higher incidence of breast cancer independent of
      geographic location and screening technology.

PMID- 24036690
TI  - Metabolic syndrome and associated chronic kidney diseases: nutritional
      interventions.
AB  - Lifestyle changes such as dietary habits, sedentary life and consumption of
      energy-dense foods that have occurred over the years has led to an epidemic of
      abdominal obesity, which in turn resulted in dramatic increase in the prevalence
      of metabolic syndrome (MetS). Different expert panels have provided various
      definitions for MetS to enable a clinical diagnosis and treatment of patients at
      risk of associated complications. Obesity and obesity mediated MetS has been
      paralleled by escalation in the incidence of chronic kidney disease (CKD). A
      better understanding of the pathophysiology of MetS and identification of
      individuals with MetS early in the life course could be important for initiating
      interventions such as lifestyle modification and dietary restrictions that form
      the basis for prevention and treatment of MetS and related co-morbidities
      including CKD. This review is intended to provide a comprehensive summary of the
      evolution of definition of MetS and association of MetS with CKD. In particular,
      mechanism of obesity and diabetes mediated CKD and emerging dietary therapies for
      MetS associated CKD will be discussed. 

PMID- 24036693
TI  - Short telomeres are frequent in hereditary breast tumors and are associated with
      high tumor grade.
AB  - Telomere shortening is a common event involved in malignant transformation.
      Critically short telomeres may trigger chromosomal aberrations and produce
      genomic instability leading to cancer development. Therefore, telomere shortening
      is a frequent molecular alteration in early stages of many epithelial tumors and
      in breast cancer correlates with stage and prognosis. A better understanding of
      the involvement of short telomeres in tumors may have a significant impact on
      patient management and the design of more specific treatments. To understand the
      role of telomere length (TL) in breast cancer etiology we measured the length of
      individual telomere signals in single cells by using quantitative telomere in
      situ hybridization in paraffin-embedded tissue from hereditary and sporadic
      breast cancers. A total of 104 tumor tissue samples from 75 familial breast
      tumors (BRCA1, n = 14; BRCA2, n = 13; non-BRCA1/2, n = 48) and 29 sporadic tumors
      were analyzed. Assessment of telomere signal intensity allowed estimation of the
      mean TL and related variables, such as percentage of critically short telomeres
      and percentage of cells with short telomeres. These data were correlated with the
      immunohistochemical expression of molecular breast cancer markers. Hereditary
      BRCA1, BRCA2, and non-BRCA1/2 tumors were characterized by shorter TL comparing
      to sporadic tumors. Considering all tumors, tumor grade was a strong risk factor
      determining the proportion of short telomeres or short telomere cells. Moreover,
      some histopathological features appeared to be differentially associated to
      hereditary or sporadic subgroups. Short telomeres correlated with ER-negative
      tumors in sporadic cases but not in familial cases, whereas a high level of
      apoptosis was associated with shorter telomeres in hereditary BRCA1 and BRCA2
      tumors. In addition, TL helped to define a subset of non-BRCA1/2 tumors with
      short telomeres associated with increased expression of antiapoptotic proteins.
      These findings highlight the potential interest of TL measurements as markers of
      aggressiveness in breast cancer.

PMID- 24036694
TI  - Systemic treatment with 4-211Atphenylalanine enhances survival of rats with
      intracranial glioblastoma.
AB  - OBJECTIVE: Increased amino acid transport in brain tumours is used for diagnostic
      purposes. It has been shown that the alpha-emitting radionuclide astatine-211
      labeled to L-phenylalanine is taken up by glioblastoma cells. We here tested, if
      systemic treatment with 4-[211At]astatine-phenylalanine (At-Phe) has a beneficial
      effect on survival of rats with intracranial glioblastoma. ANIMALS, METHODS: The
      rat glioblastoma cell line BT4Ca was implanted into the prefrontal cortex of
      female BDIX rats by stereotaxic microinjection (10,000 cells/3 ul; n = 83). 3
      days after implantation At-Phe or phosphate buffered saline were injected
      intravenously. A third group was treated twice, i.e., on day 3 and 10. Health
      condition was assessed each day by using a score system. Rats were sacrificed on
      days 6, 10, 13 and 17 after implantation, or when showing premortal health
      condition to measure tumour volume and necrosis. The proliferation index (PI) was
      assessed after immunohistochemical staining of Ki-67. RESULTS: Survival time of
      rats treated twice with At-Phe was significantly prolonged. Additionally, both At
      Phe-treated groups remained significantly longer in a better health condition.
      Rats with poor health status had larger tumours than rats with fair health
      condition. Overall, irrespective of treatment the PI was reduced in rats with
      poor health condition. Necrosis was larger in rats treated twice with At-Phe.
      CONCLUSION: Intravenous treatment with At-Phe enhanced survival time of rats with
      intracranial glioblastomas and improved health condition. These results encourage
      studies using local treatment of intracranial glioblastoma with At-Phe, either by
      repeated local injection or by intracavital application after tumour resection.

PMID- 24036695
TI  - The long non-coding RNA Fendrr links epigenetic control mechanisms to gene
      regulatory networks in mammalian embryogenesis.
AB  - Epigenetic control mechanisms determine active and silenced regions of the
      genome. It is known that the Polycomb Repressive Complex 2 (PRC2) and the
      Trithorax group/Mixed lineage leukemia (TrxG/Mll) complex are able to set
      repressive and active histone marks, respectively. Long non-coding RNAs (lncRNAs)
      can interact with either of these complexes and guide them to regulatory
      elements, thereby modifying the expression levels of target genes. The lncRNA
      Fendrr is transiently expressed in lateral mesoderm of mid-gestational mouse
      embryos and was shown to interact with both PRC2 and TrxG/Mll complexes in vivo.
      Gene targeting revealed that loss of Fendrr results in impaired differentiation
      of tissues derived from lateral mesoderm, the heart and the body wall, ultimately
      leading to embryonic death. Molecular data suggests that Fendrr acts via
      dsDNA/RNA triplex formation at target regulatory elements, and directly increases
      PRC2 occupancy at these sites. This, in turn, modifies the ratio of repressive to
      active marks, adjusting the expression levels of Fendrr target genes in lateral
      mesoderm. We propose that Fendrr also mediates long-term epigenetic marks to
      define expression levels of its target genes within the descendants of lateral
      mesoderm cells. Here we discuss approaches for lncRNA gene knockouts in the
      mouse, and suggest a model how Fendrr and possibly other lncRNAs act during
      embryogenesis. 

PMID- 24036697
TI  - Manipulating assembly of cationic dipeptides using sulfonic azobenzenes.
AB  - Three sulfonic azobenzenes with tiny differences in the terminal were used to
      manipulate the assembly of cationic dipeptides (CDP); assemblies with diverse
      morphologies including urchin-like, flower-like and plate-like structures were
      formed. 

PMID- 24036696
TI  - Mild hypothermia protects against oxygen glucose deprivation (OGD)-induced cell
      death in brain slices from adult mice.
AB  - Most of neuroprotective strategies in stroke have failed to move from bench to
      bedside. One explanation might be the use of excessive uniform and smooth
      experimental models. Therefore, we have employed a more stringent in vitro model
      based on cultured brain slices from adult mice submitted to OGD. Using this acute
      model, we have confirmed that mild hypothermia protects against OGD-induced cell
      death when cooling the tissue during and after OGD, but not when hypothermia is
      induced only during reoxygenation. 

PMID- 24036698
TI  - On the validity of time-dependent AUC estimators.
AB  - Recent developments in molecular biology have led to the massive discovery of new
      marker candidates for the prediction of patient survival. To evaluate the
      predictive value of these markers, statistical tools for measuring the
      performance of survival models are needed. We consider estimators of
      discrimination measures, which are a popular approach to evaluate survival
      predictions in biomarker studies. Estimators of discrimination measures are
      usually based on regularity assumptions such as the proportional hazards
      assumption. Based on two sets of molecular data and a simulation study, we show
      that violations of the regularity assumptions may lead to over-optimistic
      estimates of prediction accuracy and may therefore result in biased conclusions
      regarding the clinical utility of new biomarkers. In particular, we demonstrate
      that biased medical decision making is possible even if statistical checks
      indicate that all regularity assumptions are satisfied. 

PMID- 24036699
TI  - The great recession of 2007 and California nurses: a descriptive analysis.
AB  - This study investigates the effect of the Recession of 2007 on nurses' wages,
      demographics, human capital, and work environment characteristics using data from
      the California Board of Registered Nursing Surveys of 2006, 2008 and 2010.
      Findings suggest that the labor force is maximized, with nurses working as much
      as they can on their primary nursing positions (51 weeks a year). As the economy
      recovers, the nurse shortage will resurge. Intense focus in three policy areas is
      recommended: education, faculty training, and recruitment and retention of
      African Americans, Hispanics, and older nurses. 

PMID- 24036701
TI  - [Prophylaxis and therapy of post-traumatic stress disorder with propranolol:
      evidence and ethical analysis].
AB  - The beta-antagonistic agent propranolol is increasingly being used in clinical
      trials for the prophylaxis and treatment of post-traumatic stress disorder
      (PTSD). This article discusses the evidence for the effectiveness of propranolol
      in the prophylaxis and treatment of PTSD and the ethical implications of research
      on these treatment approaches. The efficacy of a prophylactic or therapeutic use
      could not be shown during the last decade. Both treatment approaches raise
      ethical questions that should already be addressed during the clinical trials. 

PMID- 24036702
TI  - [Introduction and transformation of the psychiatric term "anancasm". From Gyula
      (Julius) Donath via Kurt Schneider to ICD-10].
AB  - The conceptual history of "anancasm" in psychiatry remains almost unexplored and
      this article will help to remove this deficit. It was the Budapest-based
      neuropsychiatrist Gyula Donath (1849-1944) who first proposed this Greek-rooted
      term in 1897 as an international term for compulsive symptoms and as an
      independent mental illness similar to present-day obsessive compulsive disorders
      (ICD-10). By suggesting this term Donath wanted to extend the concept of
      compulsion as proposed by his teacher Carl Westphal to other compulsive
      phenomena, psychomotor impulses and restrictions including echolalia, coprolalia,
      echokinesis, echopraxia, contemporary maladie des tics (present day Tourette's
      syndrome) and even intermittent dipsomania (craving for alcohol), paraphilias,
      sexual fetishes and homosexuality. In 1923 Kurt Schneider used this term for a
      subgroup of psychopathic personalities, the so-called insecure anancastic
      psychopaths. His concept was much different to that suggested by Donath, with the
      only thing in common being the compulsory component. Schneider's anancasts
      suffered from feelings of insecurity and insufficiency and were forced to try to
      overcompensate by being excessively careful, meticulous and hyper-correct. Based
      on Schneider's concept anancasm has survived as a name for a subdivision of
      compulsive personality disorders in ICD-10; however, these rather complex
      personality defects were not what Donath had in mind when he first suggested the
      term anancasm. The paper discusses further discrepancies between Donath,
      Schneider and ICD-10. 

PMID- 24036703
TI  - [University teaching in clinical neurology: present situation and future
      requirements].
AB  - BACKGROUND: In German Hospitals there is a lack of medical personnel and doctors
      in particular. Clinical specialities and hospitals are in competition for
      students and young doctors and these, in turn, have clear cut demands regarding
      working conditions and professional training. To date there is considerable
      heterogeneity regarding clinical teaching in neurology between different German
      universities. There are no data available for systematic comparison. MATERIAL AND
      METHODS: This article presents for the first time data from a survey on academic
      teaching in neurology in German university hospitals. RESULTS AND CONCLUSION: The
      data show that many faculties are dedicated to modern and practical teaching
      methods and have employed state of the art examinations and progress tests.
      Further and ongoing efforts will be needed in order to inspire medical students
      and young doctors for this interesting clinical speciality. Connecting individual
      formats and networking between universities, teaching hospitals, including novel
      developments together with the young neurologists will help to structure our
      efforts and increase sustained attractiveness of clinical neurology for the
      following generations of young doctors.

PMID- 24036713
TI  - A novel technology: percutaneous injection of fibrin glue as a treatment for
      frontal sinus cerebrospinal fluid rhinorrhea.
AB  - In this study, we examined the effectiveness of percutaneous injected fibrin glue
      as a treatment for frontal sinus cerebrospinal fluid (CSF) rhinorrhea in a series
      of 4 cases. All 4 patients had fracture in the posterior wall of the frontal
      sinus. The anterior wall of the frontal sinus was punctured following high
      resolution computed tomography imaging. In 3 out of 4 patients with defective
      skull due to prior frontal craniotomy, direct percutaneous puncture of the
      frontal sinus was used. Fibrin glue was injected to close the fistula and to seal
      the rhinorrhea. Surgery procedures lasted for 15-35 minutes (average 27.6 min).
      Rhinorrhea was stopped in all patients after the surgery, with no recurrence at a
      10-month follow-up visit. In 1 case, the glue was expelled by coughing at 2 days
      after the surgery but was completely stopped with no recurrence after a second
      attempt. One patient with no recurrence at a 10-month follow-up died of tumor
      relapse at 12 months. In summary, fibrin glue could be used as a novel treatment
      for frontal sinus CSF rhinorrhea. 

PMID- 24036715
TI  - Ethics, safety and excellence as a future slogan that need appropriation.

PMID- 24036716
TI  - Influence of acidic fibroblast growth factor on bone regeneration in experimental
      cranial defects using spongostan and Bio-Oss as protein carriers.
AB  - The objective of this study was to valuate 2 substances as potential carriers of
      fibroblast growth factor 1 (FGF-1) in a rat craniectomy model: gelatin sponge
      (Spongostan; Ferrosan A/S, Soborg, Denmark) and natural bone mineral (Bio-Oss;
      Geistlich Biomaterials, Wolhusen, Switzerland).Forty-eight adult male Sprague
      Dawley rats were used. A 5-mm-diameter circular craniectomy was performed in the
      left parietal bone. Animals were divided into 6 experimental groups of 8 rats,
      each group receiving a different treatment: control (no substance added),
      Spongostan, Bio-Oss, FGF, FGF + Spongostan, and FGF + Bio-Oss. Animals were
      killed 12 weeks after surgery.Descriptive histology and stereology were used, the
      latter to measure the volumes of regenerated bone and Bio-Oss remaining in the
      defect. Analysis of variance was used to determine differences in bone
      regeneration between groups, and Mann-Whitney U test was used to compare the
      volume of remaining Bio-Oss particles.Histologically, the control defects behaved
      like critical size defects, showing incomplete bone regeneration. Only the FGF +
      Spongostan group achieved nearly complete bone regeneration. Bio-Oss particles
      seemed to reduce centripetal bone regeneration. Spongostan by itself did not
      interfere with spontaneous bone healing.Stereologic measurements of the volume of
      new bone growth, measured in cubic millimeter, were as follows: control group,
      3.86 +/- 1.03; Bio-Oss, 2.26 +/- 1.06; Spongostan, 3.00 +/- 0.81; FGF, 3.99 +/-
      1.85; FGF + Bio-Oss, 3.02 +/- 1.88; and FGF + Spongostan, 8.93 +/- 1.28. Analysis
      of variance showed a statistically significant difference between the FGF +
      Spongostan group and the other groups (P < 0.001). Comparison among the other
      groups did not show significant differences.Fibroblast growth factor 1 with a
      Spongostan carrier has shown great efficacy for bone regeneration in cranial
      critical size defects in rats. Bio-Oss did not produce a regenerative effect,
      either alone or with FGF-1. 

PMID- 24036717
TI  - A psychological analysis of the Korean mothers of cleft lip and palate patients:
      screening for psychological counseling and neuropsychiatric treatment.
AB  - The purpose of this study is to examine the psychological states and the stress
      levels of the Korean mothers who have cleft lip and palate child patients. The
      authors explored whether psychological assessments of the mothers with child
      patients could play a role in screening for psychiatric counseling. Thirty-six
      mothers of child patients admitted to receive cleft lip and palate surgery at
      Seoul National University Children's Hospital were recruited as subjects of this
      study. The 3 questionnaires included in the study were the Beck Depression
      Inventory, Beck Anxiety Inventory, and Parenting Stress Inventory. We compared
      these results with those of general population according to the domestic studies.
      The statistical significances of these results were analyzed using Mann-Whitney
      method. The average score from the Beck Depression Inventory was 8.89 with
      standard deviation of 6.08. The average score from the Beck Anxiety Inventory was
      9.69 with standard deviation of 6.89. In the Parenting Stress Inventory, the
      average score was 55.06 and standard deviation was 16.45. However, there were no
      statistically significant differences between mothers whose children have
      underwent surgery versus no surgery and mothers whose children had visible versus
      invisible anomalies. The reliable psychological analysis of depression, anxiety,
      and stress levels of the mothers of child patients allowed the authors to assess
      the psychological states of the mothers of child patients. Such assessment can
      play a vital role in the screening of candidates who need psychiatric treatment
      or consultation. 

PMID- 24036718
TI  - Odontogenic tumors.
AB  - PURPOSE: This study aims to analyze the frequency and distribution of odontogenic
      tumors in a Greek population and compare the findings with those reported in the
      recent literature. METHODS: Records of the Department of Oral Medicine and
      Pathology, Dental School, University of Athens, with histologic diagnosis of
      odontogenic tumors (based on the World Health Organization 2005 classification)
      were reviewed retrospectively from January 1970 to December 2011. RESULTS: A
      total of 652 cases of odontogenic tumors were reported. Of these, 651 (99.8%)
      were benign and only 1 (0.2%) was malignant. Keratocystic odontogenic tumor was
      the most frequent lesion (52.7%), followed by odontoma (18.9%) and ameloblastoma
      (16.1%). The mean age of patients was 38.0 years with a wide range (2.5-92
      years). CONCLUSIONS: Odontogenic tumors are rare lesions and appear to show a
      definite geographic variation. In Athens, Greece, they are presented mainly by
      the keratocystic odontogenic tumor, odontoma, and ameloblastoma.

PMID- 24036719
TI  - Systematic evaluation on the use of acellular dermis matrix graft in prevention
      Frey syndrome after parotid neoplasm surgery.
AB  - OBJECTIVE: To study the effectiveness and safety of acellular dermal matrix (ADM)
      graft in preventing Frey syndrome after parotid neoplasm surgery, we reviewed
      foreign reported clinical randomized controlled trials systematically. Based on
      this review, we aimed to assess the effectiveness of ADM graft and provide
      reliable evidence for clinical application. METHODS: We reviewed foreign-language
      databases, such as MEDLINE, applied meta-analysis with Rev.Man 5, and drew forest
      plots with odds ratio as effect size. RESULTS: Three trials were recruited. The
      morbidity of Frey syndrome in experimental group was significantly lower than
      that in control on both subjective index and objective index, with odds ratios at
      0.03 (95% confidence interval, 0.01-0.11) and 0.03 (95% confidence interval, 0.01
      0.12), respectively. There was no significant difference between ADM group and
      blank control in total adverse reactions and complication incidence, whereas
      results differed for a kind of specific adverse reaction or complication.
      CONCLUSIONS: Based on existing research data, implanting ADM could effectively
      prevent Frey syndrome, and its poor prognosis effects did not significantly
      increase, which suggested that its total safety was reliable. Nevertheless,
      further investigations about the difference on a specific adverse reaction or
      complication were still needed.

PMID- 24036720
TI  - Suitable indication for the application of distraction osteogenesis: occipital
      enlargement for lambdoid synostosis.
AB  - In recent years, cranial distraction osteogenesis (DOG) for craniosynostosis has
      often been performed in Japan. Since 1998, DOG has been conducted in more than 80
      patients with craniosynostosis in our institution. It is now important to define
      the appropriate indications for the application of DOG for craniosynostosis. From
      the point of view of our more than 10 years of experience with the application of
      cranial DOG, posterior enlargement is one of the most appropriate applications.
      Bilateral posterior expansion is conducted for hypertension because of bilateral
      lambdoidal synostosis, whereas unilateral posterior expansion is conducted for
      asymmetry because of unilateral posterior plagiocephaly. Posterior expansion by
      gradual distraction was conducted for 12 cases. Eight cases of syndromic
      craniosynostosis and 4 of simple unilateral lambdoid synostosis were included.
      Clinical and radiological improvement was observed in all cases. Postdistraction
      computed tomography demonstrated a decrease in digital printing within a few
      months in all cases. Distraction osteogenesis is a useful procedure for posterior
      enlargement by gradual expansion and guarantees postdistraction rigidity without
      collapse in a supine position in bilateral and unilateral lambdoid synostosis. 

PMID- 24036721
TI  - Condylar repositioning in bilateral sagittal split ramus osteotomy with centric
      relation bite.
AB  - PURPOSE: Changes in the condylar position after bilateral sagittal split ramus
      osteotomy (BSSO) can cause many complications, such as condylar dysfunction and
      increased risk of relapse. This study evaluated a simple approach for condylar
      repositioning in BSSO as a method to rapidly obtain the patient's centric
      relation (CR) bite position without prefabricated equipment. METHODS: The study
      subjects included 9 patients (5 men and 4 women; mean age, 23.7 years) who
      underwent BSSO in the Department of Oral and Maxillofacial Surgery in Hallym
      University hospital between December 2009 and March 2012. We performed BSSO with
      the condylar-repositioning method according to the patient's CR bite. RESULTS:
      Measurements of changes in the condylar position via radiographic images (lateral
      cephalometric radiographs) did not indicate significant differences after surgery
      (P < 0.05). In surveys of temporomandibular joint symptoms, the scores for
      categories (sound, pain, mouth opening limitation) also did not show any
      increases after surgery. CONCLUSIONS: Within a standard operating time, the
      condyle was effectively repositioned using the condylar-repositioning method
      described in this study. These results indicate this new repositioning method is
      simple and eliminates the need for any additional device.

PMID- 24036722
TI  - Culture and identification of human bone marrow mesenchymal stem cells from
      alveolar ridge dental implant site.
AB  - OBJECTIVE: The objective of this study was to establish the culture method of
      human bone marrow mesenchymal stem cells (BMSCs) from alveolar bone marrow.
      METHODS: Alveolar bone marrow complex samples were obtained from 35 patients, 22
      to 65 years of age, during the course of dental implant treatment by low-speed
      method. Bone marrow mesenchymal stem cells were seeded and maintained in culture
      with 10% fetal bovine serum. The form of the cultured cells was observed under
      inverted microscope, and the cell proliferation capacity was detected. Cell cycle
      and the antigen expression of P3 BMSCs were measured with flow cytometry.
      RESULTS: From a small volume (about 0.1-0.2 mL) of bone marrow complex, alveolar
      BMSCs expanded at a success ratio of 29 (83%) of 35. There is dysmorphism in
      cultured cells, which mainly were long spindle, polygon, and triangle. Flow
      cytometry instrument test showed that the cells in G0/G1 phase were an average of
      79.29% +/- 1.70% and in S phase were an average of 11.09% +/- 0.87%. For antibody
      expression rate: CD29 is 88.00% +/- 1.56%, CD44 is 88.15% +/- 1.64%, CD34 is
      0.42% +/- 0.10%, CD45 is 0.45% +/- 0.12%, and CD11b is 0.45% +/- 0.14%.
      CONCLUSION: The cells of the marrow complex obtained by low-speed method in
      implant site preparation cultured in vitro were identified as BMSCs through the
      morphological observation and the flow cytometry. It is a kind of feasible and
      simple culture method of human primary BMSCs.

PMID- 24036723
TI  - Association of facial asymmetry and nasal septal deviation in acquired
      nasolacrimal duct obstruction in East Asians.
AB  - PURPOSE: The objective of this study was to evaluate the association of facial
      asymmetry and nasal septal deviation in acquired unilateral nasolacrimal duct
      (NLD) obstruction. METHODS: A retrospective survey was conducted of 39 patients
      (6 male and 33 female) who had undergone endoscopic dacryocystorhinostomy at the
      Korea University Ansan Hospital. Patients with trauma to the orbit or any known
      lacrimal duct disease were excluded. The primary goal was to obtain a descriptive
      analysis of facial asymmetry and nasal septal deviation. We analyzed the results
      and identified associations with facial asymmetry and nasal septal deviation in
      NLD obstruction and determined the influence of the degree of asymmetry and
      deviation on the results. RESULTS: The mean length of the straight line drawn
      from the lateral canthus to the corner of the mouth was 10.2 cm in the right eye
      and 9.9 cm in the left eye, and the difference was statistically significant by
      the Wilcoxon signed rank test (P = 0.043). The laterality of NLD obstruction
      corresponded to the smaller side of the face in 27 of 39 patients (P = 0.038,
      kappa = 0.753 by cross-table McNemar test). Also, a significant positive linear
      relation of correspondence of NLD obstruction to the smaller side of the face was
      observed according to the degree of facial asymmetry (P = 0.043 by linear-by
      linear association). Nasolacrimal duct obstruction appeared to occur on the side
      in which the nasal septum was deviated in 25 of 39 patients (P = 0.043, kappa =
      0.652 by cross-table McNemar test). Significant positive linear relation of
      correspondence of NLD obstruction to the side in which the nasal septum was
      deviated was also observed according to the degree of nasal septal deviation (P =
      0.045 by linear-by-linear association). There is also a trend of nasal septal
      deviation toward the smaller side of the face (total 25 of 39 patients, P = 0.043
      by cross-table McNemar test). CONCLUSIONS: Unilateral NLD obstruction appears to
      occur on the side in which the nasal septum is deviated, and nasal septal
      deviation tends to be toward the smaller side of the face. Also, the degree of
      facial asymmetry and nasal septal deviation may affect NLD obstruction. This
      study showed that facial asymmetry and nasal septal deviation could be a cause of
      unilateral NLD obstruction. This finding can aid in differentiating lacrimal duct
      obstruction, especially when combined with physical examination.

PMID- 24036724
TI  - The contribution of computed tomography to nasal septoplasty.
AB  - PURPOSE: The aim of this study was to determine the contribution of computed
      tomography (CT) scanning to nasal septoplasty. METHODS: The study included 76
      patients, on whom septoplasty was planned to be performed because of deviated
      nasal septum. The patients were divided into 2 groups: those who had a CT scan
      (group 1, study group) and those who did not have a CT scan (group 2, control
      group) before septoplasty. Pathologic anatomic structures accompanying deviated
      septum and surgical interventions performed in addition to septoplasty were
      determined. The patients were asked the degree of improvement in nasal air
      passage obstruction, and 2 groups were compared with each other. RESULTS: Group 1
      included 40 patients, and group 2 had 36 patients. In group 1, the pathologic
      findings determined along with deviated septum were concha bullosa in 14
      patients, retention cyst of the maxillary sinus in 2 patients, paradox middle
      nasal concha in 2 patients, inferior concha hypertrophy in 18 patients, frontal
      osteoma in 1 patient, antrochoanal polyp in 1 patient, and chronic sinusitis
      (maxillary, ethmoidal, frontal) in 7 patients. Lateral resection was performed
      for concha bullosa; out-fracture with submucosal cauterization was performed on
      the patients with inferior concha hypertrophy, and endoscopic sinus surgery was
      performed for the patients with chronic sinusitis and antrochoanal polyp.
      CONCLUSIONS: Computed tomography is able to recognize some pathologic findings
      that cannot be found on physical examination and is helpful to decide the
      location and the type of the surgery. Additional surgical interventions owing to
      CT performed before the septoplasty are much more helpful to relieve the
      patient's nasal air passage obstruction.

PMID- 24036725
TI  - Evaluation of stability changes in magnesium-incorporated titanium implants in
      the early healing period.
AB  - The aim of the present study was to determine the bone response to magnesium (Mg)
      ion-incorporated titanium (Ti) implants during the early healing period. A total
      of 114 patients (69 men and 45 women aged between 29 and 71 years) participated
      in the study. Overall, one hundred thirty-three 10-mm-long fixtures were
      installed, composed of 65 Mg ion-incorporated fixtures in the test group (55
      participants; 30 males and 25 females) and 68 resorbable blast media (RBM)
      surface fixtures in the control group (59 participants; 39 males and 20 females).
      The bone responses were evaluated by resonance frequency analysis (RFA) at the
      following time points after implant insertion (ie, the healing period): 0, 2, 4,
      8, and 12 weeks. Each time an RFA measurement was taken, the stability changes
      relating to both bone quality and implant arch location (maxilla or mandible)
      were recorded for further analysis. The mean stabilities were lowest at week 4 of
      healing for both the test and control groups. Significant differences in RFA
      values between the 2 groups were found at week 12 of healing. The mean percentage
      change in implant stability quotient (ISQ) from the baseline revealed that the
      implant stability of the Mg ion-incorporated test group had increased (4.55%)
      more than the RBM surface group (2.23%) by week 12 of healing. With respect to
      bone quality, the mean ISQ of Mg-incorporated Ti implants only changed
      significantly during the 12-week period for type 4 bone. Furthermore, at weeks 4
      and 12 of healing, significant differences were found between the 2 groups for
      type 2 and type 4 bone. A comparison of the stability patterns of mandibular and
      maxillary implants revealed that the overall stability was higher in the
      mandible; however, no significant difference was found for Mg-incorporated Ti
      implants. The Mg-incorporated Ti implants exhibited a slightly better bone
      response with respect to ISQ than did the RBM surface implants, and the
      percentage change in mean ISQ from the baseline was greater for the Mg
      incorporated group than for the RBM surface group at the end point of this study.

PMID- 24036726
TI  - Lacunocanalicular fluid flow transduces mechanical tension stress during
      distraction osteogenesis.
AB  - The mechanotransduction mechanisms linking distraction device activation to new
      bone formation remain unknown. We hypothesize that the tension stress of
      activation during distraction osteogenesis is transmitted through
      lacunocanalicular fluid flow to initiate the osteogenic signaling cascade. Adult
      Sprague-Dawley rats (N = 24) were subjected to mandibular osteotomy and
      application of an external distraction device. After a 3-day latency period, half
      the animals (n = 12) underwent device activation at 0.25 mm twice daily for 6
      days (total activation, 3 mm), and the other half (n = 12) had no activation. On
      day 10, the animals were injected with fluorescent reactive red lacunocanalicular
      tracer before killing. Mandibles were harvested, embedded, and sectioned, and
      reactive red epifluorescence lacunocanalicular flow was measured. Protein was
      harvested for focal adhesion kinase 1 (FAK1), NESPRIN1, SUN1, LAMIN A/C, and
      SMAD1 Western blotting as well as for bone morphogenetic protein (BMP)-2 enzyme
      linked immunosorbent assay and alkaline phosphatase assay. Lacunocanalicular
      fluid flow was significantly greater in the distracted samples (60.5 +/- 14 vs
      10.3 +/- 4 molecules of equivalent soluble fluorochrome per megapixel, P = 0.01).
      Flow distribution demonstrated the highest lacunocanalicular flow near the center
      of the distraction gap. Increased lacunocanalicular flow resulted in increased
      FAK1 (P = 0.009), NESPRIN1 (P = 0.01), SUN1 (P = 0.01), and LAMIN A/C (P = 0.008)
      expression. Focal adhesion kinase 1 activation in the presence of BMP-2 protein
      expression (P = 0.001) resulted in increased intranuclear SMAD1 phosphorylation
      (P = 0.04) and alkaline phosphatase activity (P < 0.0001). These findings suggest
      that activation of the distraction osteogenesis device affects cellular response
      through changes in lacunocanalicular fluid flow. 

PMID- 24036727
TI  - Three-dimensional courses of zygomaticofacial and zygomaticotemporal canals using
      micro-computed tomography in Korean.
AB  - The zygomatic nerve (ZN), which originates from the maxillary nerve at the
      pterygopalatine fossa, enters the orbit through the inferior orbital fissure.
      Within the lateral region of the orbit, the ZN divides into the zygomaticofacial
      (ZF) and zygomaticotemporal (ZT) nerves. The ZF and ZT nerves then pass on to the
      face and temporal region through the zygomaticoorbital foramen and enter their
      own bony canals within the zygomatic bone. However, multiple zygomaticofacial and
      zygomaticotemporal canals (ZFCs and ZTCs, respectively) can be observed, and
      their detailed intrabony courses are unknown. The aim of this study was clarify
      the three-dimensional intrabony courses and running patterns of the ZFCs and
      ZTCs, both to obtain a detailed anatomical description and for clinical purposes.
      Fourteen sides of the zygomatic bones were scanned as two-dimensional images
      using a micro-computed tomography (CT), with 32-MUm slice thickness. Intrabony
      structures of each canals were three-dimensionally reconstructed and analyzed
      using Mimics computer software (Version 10.01; Materialise, Leuven, Belgium). We
      found that some ZTC was originated from ZFC. In 71.4% of the specimens, the
      ZTC(s) divided from the intrabony canal along the course of the ZFC(s). In other
      cases, 28.6% of ZTCs were opened through each corresponding ZT foramen.
      Zygomaticofacial canal originates from zygomaticoorbital foramen, divided into
      some of ZTCs, and is finally opened as ZF foramen. This new anatomical
      description of the intrabony structures of the ZFC(s) and ZTC(s) within the
      zygomatic bone by micro-CT technology provided helpful information to surgeons
      performing clinical procedures such as Le Fort osteotomy and reconstructive
      surgeries in the midface region. 

PMID- 24036728
TI  - Bilateral nasoseptal flaps for endoscopic endonasal transsphenoidal approach.
AB  - A nasoseptal flap is used to reconstruct defects in the skull base when
      cerebrospinal fluid (CSF) leaks after the endoscopic endonasal transsphenoidal
      approach (EETSA). We evaluated the usefulness of elevating bilateral nasoseptal
      flaps with the EETSA. Sixty-seven patients (71 procedures, including 4 revisions)
      underwent the EETSA with bilateral nasoseptal flap elevation. We retrospectively
      reviewed patients' medical records, including demographic data, surgical
      procedures, outcomes, and complications. The entire sellar floor was exposed
      after elevating bilateral nasoseptal flaps. We reconstructed the defect using a
      right nasoseptal flap in 14 cases with intraoperative CSF leakage. The denuded
      sphenoidal sinus was covered with a left nasoseptal flap in 13 cases with
      excessive loss of sphenoidal sinus mucosa. Unused flaps (57 right flaps and 58
      left flaps) were repositioned in the original sites. No postoperative CSF leak
      occurred. All sphenoidal sinuses covered with the left nasoseptal flap healed
      well without excessive crust. Two patients experienced immediate postoperative
      bleeding. Septal perforation occurred in 1 patient who underwent a revision
      operation. Bilateral nasoseptal flap elevation provided good exposure of the
      sellar floor with the EETSA. The nasoseptal flap could be used to reconstruct the
      defect after the EETSA and to cover the denuded sphenoidal sinus. The unused
      flaps could be repositioned in their original sites to minimize the septal defect
      and could be reused in revision surgery. We suggest that elevating bilateral
      nasoseptal flaps is a useful surgical technique in a variety of settings with the
      EETSA. 

PMID- 24036729
TI  - Image fusion in craniofacial virtual reality modeling based on CT and 3dMD
      photogrammetry.
AB  - PURPOSE: The aim of this study was to demonstrate the feasibility of building a
      craniofacial virtual reality model by image fusion of 3-dimensional (3D) CT
      models and 3 dMD stereophotogrammetric facial surface. METHODS: A CT scan and
      stereophotography were performed. The 3D CT models were reconstructed by
      Materialise Mimics software, and the stereophotogrammetric facial surface was
      reconstructed by 3 dMD patient software. All 3D CT models were exported as Stereo
      Lithography file format, and the 3 dMD model was exported as Virtual Reality
      Modeling Language file format. Image registration and fusion were performed in
      Mimics software. Genetic algorithm was used for precise image fusion alignment
      with minimum error. The 3D CT models and the 3 dMD stereophotogrammetric facial
      surface were finally merged into a single file and displayed using Deep
      Exploration software. Errors between the CT soft tissue model and 3 dMD facial
      surface were also analyzed. RESULTS: Virtual model based on CT-3 dMD image fusion
      clearly showed the photorealistic face and bone structures. Image registration
      errors in virtual face are mainly located in bilateral cheeks and eyeballs, and
      the errors are more than 1.5 mm. However, the image fusion of whole point cloud
      sets of CT and 3 dMD is acceptable with a minimum error that is less than 1 mm.
      CONCLUSIONS: The ease of use and high reliability of CT-3 dMD image fusion allows
      the 3D virtual head to be an accurate, realistic, and widespread tool, and has a
      great benefit to virtual face model.

PMID- 24036730
TI  - Morphomic measurement of the temporalis muscle and zygomatic bone as novel
      predictors of hospital-based clinical outcomes in patients with mandible
      fracture.
AB  - INTRODUCTION: Patients with mandibular fracture often have comorbidities and
      concomitant injuries making the decision for when and how to operate a challenge.
      Physicians describe "temporalis wasting" as a finding that indicates frailty;
      however, this is a subjective finding without quantitative values. In this study,
      we demonstrate that decreased morphomic values of the temporalis muscle and
      zygomatic bone are an objective measure of frailty associated with increased
      injury-induced morbidity as well as negative impact on overall hospital-based
      clinical outcomes in patients with mandible fracture. METHODS: Computed
      tomographic (CT) scans from all patients with a diagnosis of a mandible fracture
      in the University of Michigan trauma registry and with a hospital admission were
      collected from the years 2004 to 2011. Automated, high-throughput CT analysis was
      used to reconstruct the anatomy and quantify morphomic values (temporalis volume,
      area and thickness, and zygomatic thickness) in these patients using MATLAB v13.0
      (MathWorks Inc, Natick, MA, USA). Subsequently, a subset of 16 individuals with a
      Glasgow Coma Scale of 14 or 15 was analyzed to control for brain injury. Clinical
      data were obtained, and the association between morphomic measurements and
      clinical outcomes was evaluated using Pearson correlation for unadjusted analysis
      and multiple regression for adjusted analysis. RESULTS: The mean age of patients
      in the study was 47.1 years. Unadjusted analysis using Pearson correlation
      revealed that decreases in zygomatic bone thickness correlated strongly with
      increases in hospital, intensive care unit, and ventilator days (P < 0.0001, P =
      0.0003, and P = 0.0017, respectively). Furthermore, we found that decreases in
      temporalis mean thickness correlated with increases in hospital and ventilator
      days (P = 0.0264 and P = 0.0306, respectively). Similarly, decreases in
      temporalis local mean thickness are significantly correlated with increases in
      hospital and ventilator days (P = 0.0232 and P = 0.0472, respectively).
      CONCLUSIONS: Decreased thicknesses of the zygomatic bone and temporalis muscle
      are significantly correlated with higher hospital, ventilator, and intensive care
      unit days in patients with mandibular fracture receiving reconstructive
      operations. This morphomic methodology provides an accurate, quantitative means
      to evaluate craniofacial trauma patient frailty, injury, and outcomes using
      routinely obtained CT scans. In the future, we plan to apply this approach to
      determine preoperative risk stratification and assist in surgical planning.

PMID- 24036731
TI  - What causes increased contrast sensitivity and improved functional visual acuity
      after upper eyelid blepharoplasty?
AB  - PURPOSE: The objective of this study was to report the cause of increased
      contrast sensitivity and improved functional visual acuity after upper eyelid
      blepharoplasty. METHODS: Twenty-two eyelids of 16 patients with dermatochalasis
      and involutional ptosis were prospectively studied. Contrast sensitivity, corneal
      topography, high-order aberration (HOA), and degree of lash ptosis were examined
      and recorded before and at 1 month after upper eyelid blepharoplasty. A Wilcoxon
      signed rank test was performed to compare the difference. RESULTS: The contrast
      sensitivity of patients significantly increased in every spatial frequency and
      light condition. Corneal topography showed no difference before and after
      blepharoplasty. Ocular HOA, especially total HOA, third-order, fourth-order,
      trefoil, coma, and second astigmatism decreased significantly after surgery (P =
      0.008, 0.011, 0.028, 0.033, 0.038, and 0.049, respectively). The degree of lash
      ptosis also decreased after blepharoplasty (P = 0.046). CONCLUSIONS: In our
      study, increased contrast sensitivity and improved functional visual acuity after
      upper eyelid blepharoplasty were caused by changes in ocular HOA and the degree
      of lash ptosis after surgery. There were no changes in corneal topography or
      astigmatism.

PMID- 24036732
TI  - The multiple osteotomized free iliac osteocutaneous flap for reconstructions of
      complex maxillofacial and oromandibular defects.
AB  - The vascularized iliac osteocutaneous flap has been used successfully for jaw
      reconstruction. To obtain a better contour of the reconstructed area in large
      upper and lower jaw resections, the transferred bone actually needs to be
      osteotomized. Single closing-wedge osteotomy of the iliac flap for mandibular
      reconstruction has been previously described. In this article, the modified
      multiple osteotomized perforator-based versatile free iliac osteocutaneous flap
      is described. Eleven cases were enrolled. Seven patients had wide anterior
      mandibular resections due to oral cavity and mandibular tumors; 3 patients had a
      defect due to explosive injury and 1 patient had complicated orbitomaxillary
      defect due to blast injury. Skin paddle was based on the perforators. In 8
      patients, the bony segment was divided into 3 segments by 2 osteotomies, whereas
      in 2 patients the bony segment was divided into 4 segments by 3 osteotomies. In
      10 cases, the flap was used for anterior mandibular defects, whereas in 1 case
      the flap was customized to fit an L-shaped defect at the naso-orbito-maxillary
      region. The overall flap success rate was 100%. No resorption or morbidity
      related to the osteotomy of the bony segments was observed. The size of
      perforator skin paddle was 6 to 8 * 15 to 18 cm. Physical and radiologic
      examinations showed proper bone healing without any additional complications. The
      modified multiple osteotomized free osteocutaneous iliac flap can provide a safe
      and versatile bony segment to be arranged and adapted to reconstruct complex
      mandibular and maxillofacial defects. 

PMID- 24036733
TI  - Dose-response effect of human equivalent radiation in the mandible.
AB  - BACKGROUND: Despite widespread use of adjuvant irradiation for head and neck
      cancer, the extent of damage to the underlying bone is not fully understood but
      is associated with pathologic fractures, nonunion, and osteoradionecrosis. The
      authors' laboratory previously demonstrated that radiation significantly impedes
      new bone formation in the murine mandible. We hypothesize that the detrimental
      effects of human equivalent radiation on the murine mandible results in a dose
      dependent degradation in traditional micro-computed tomography (micro-CT)
      metrics. METHODS: Fifteen male Sprague-Dawley rats were randomized into 3
      radiation dosage groups: low (5.91 Gy), middle (7 Gy), and high (8.89 Gy),
      delivered in 5 daily fractions. These dosages approximated 75%, 100%, and 150%,
      respectively, of the biologically equivalent dose that the human mandible
      receives during radiation treatment. Hemimandibles were harvested 56 days after
      radiation and scanned using micro-CT. Bone mineral density, tissue mineral
      density, and bone volume fraction were measured along with microdensitometry
      measurements. RESULTS: Animals demonstrated dose-dependent adverse effects of
      mucositis, alopecia, weight loss, and mandibular atrophy with increasing
      radiation. Traditional micro-CT parameters were not sensitive enough to
      demonstrate statistically significant differences between the radiated groups;
      however, microdensitometry analysis showed clear differences between radiated
      groups and statistically significant changes between radiated and nonradiated
      groups. CONCLUSIONS: The authors report dose-dependent and clinically significant
      adverse effects of fractionated human equivalent radiation to the murine
      mandible. The authors further report the limited capacity of traditional micro-CT
      metrics to adequately capture key changes in bone composition and present
      microdensitometric histogram analysis to demonstrate significant radiation
      induced changes in mineralization patterns.

PMID- 24036734
TI  - Treatment outcomes of implants performed after regenerative treatment of absorbed
      alveolar bone due to the severe periodontal disease and endoscopic surgery for
      maxillary sinus lift without bone grafts.
AB  - OBJECTIVE: We have developed a regenerative medicine therapy for the alveolar
      bone and endoscopic surgery for maxillary sinus lift without bone grafts, in
      patients experiencing severe periodontal disease with significant absorption of
      the maxillary alveolar bone, in which more than 10 mm of bone thickness in the
      maxillary bone was attained, with satisfactory results. The objective of this
      study was to examine the treatment outcomes of implants that were performed after
      these therapies. PARTICIPANTS AND METHODS: The participants were 36 patients with
      severe periodontal disease, who cannot be cured with any other treatments except
      the extirpation of all teeth. The 36 patients are all patients who underwent
      regenerative treatment of the alveolar bone through tooth replantation and
      transplantation of the iliac cancellous bone (the bone marrow) as well as
      endoscopic surgery for maxillary sinus lift from May 2003 to July 2007 in our
      clinic. A total of 120 implants were placed in these patients when the replanted
      teeth fell out because of root resorption, and the success rate was examined.
      RESULTS: The success rates of the implants were 16 of 33 (48%) in the group when
      surveyed less than 2 years after the surgery and 84 of 87 (96.5%) in the group
      when surveyed more than 2 years after the surgery. A statistically significant
      difference was found between the 2 groups (Chi-squared test, P < 0.001).
      CONCLUSIONS AND CONSIDERATIONS: It was believed that it takes approximately 2
      years for the bones in the maxillary sinus floor, augmented through endoscopic
      surgery for maxillary sinus lift, to attain the thickness and hardness required
      for implant placement. Therefore, although the implant treatment should be
      performed later than 2 years after surgery, chewing is possible during this
      period, with the replanted teeth that were used for regenerative treatment of the
      alveolar bone. It is believed that this is an extremely effective treatment
      method to improve the patients' quality of life.

PMID- 24036735
TI  - Ossification of subperiosteal hematoma: the potential of periosteal osteogenesis
      in cranioplasty.
AB  - BACKGROUND: Subperiosteal hematoma is the accumulation of blood between the
      periosteum and the skull, which commonly occurs in the neonatal period but rarely
      in other ages. Subperiosteal hematoma can be self-absorbed in most cases and
      occasionally may cause ossification. MATERIALS AND METHODS: This study reports a
      case of subperiosteal hematoma formed in a 16-year-old adolescent boy after a
      minor trauma. Because the hematoma did not disappear for more than a month after
      the trauma, the patient was treated with multiple hematoma punctures. However,
      the hematoma recurred and led to ossification. Finally, the patient underwent
      surgical treatment. RESULTS: Finally, the ossification associated with the
      hematoma was treated through surgery. The head contour recovered normally.
      CONCLUSIONS: The occurrence of hematoma ossification in the 16-year-old patient
      suggests that the periosteum has great potential for osteogenesis. This is likely
      caused by the joint action of some active factors in the blood and a certain
      tension of the hematoma on the local periosteum. This case provides the following
      thoughts. (1) A subperiosteal hematoma that has not been absorbed after 1 month
      should be treated promptly to avoid ossification. Once ossification has occurred,
      the hematoma should be treated surgically. (2) The potential for periosteal
      osteogenesis is great, which may provide a new thought for cranioplasty.

PMID- 24036736
TI  - Management of cranial bone defects: a reconstructive algorithm according to
      defect size.
AB  - INTRODUCTION: Reconstruction of cranial bone defects is one of the most
      challenging problems in reconstructive surgery. The timing of reconstruction, the
      location of the defect, the materials to be used, and the medical history of the
      patient are parameters that have been mostly discussed in the literature. To the
      best of our knowledge, there has not been any published classification for the
      cranial bone defect reconstruction according to defect size. MATERIALS AND
      METHODS: Twelve patients underwent reconstruction of cranial vault defects.
      Cranial bone defects were classified into 3 groups according to the size of the
      defect. The small-sized group included the defects smaller than 25 cm(2), the
      medium-sized group included the defects between 25 to 200 cm(2), and the large
      sized group included the defects larger than 200 cm(2). The small-sized defects
      were reconstructed with split calvarial graft, demineralized bone matrix, or
      hydroxyapatite cement; the medium-sized defects were reconstructed with split
      calvarial graft or allogenic bone graft; and the large-sized defects were
      reconstructed with methyl methacrylate, autoclaved bone, or porous polyethylene.
      RESULTS: Two patients needed revision for irregularities with demineralized bone
      matrix. Other patients had no skull defects or irregularities for which revision
      was suggested. CONCLUSIONS: We believe that the size of the defect is important
      for the reconstruction of cranial vault defects and that using a standard
      algorithm can increase the success rate.

PMID- 24036737
TI  - Autologous fat graft in scar treatment.
AB  - INTRODUCTION: Regenerative medicine is an emerging and rapidly evolving field of
      research and therapy, thanks to new discoveries on stem cells. Adipose tissue is
      a connective tissue which contains a reserve of mesenchymal stem cells. Clinical
      improvements in trophic characteristics of teguments after autologous fat graft
      are well described in literature. In this paper, we present our observation after
      6 years of autologous fat graft experience in scar remodeling. MATERIALS AND
      METHODS: All patients recruited had retractile and painful scars compromising the
      normal daily activity/mobility of the joint involved. We performed surgical
      procedure with Coleman technique. In 20 patients, we performed a clinical
      assessment using Patient and Observer Scar Assessment Scale (POSAS) and Durometer
      measurements. RESULTS: In all treated scars, a qualitative improvement was shown
      both from an aesthetic and functional point of view. Most importantly, reduction
      or complete resolution of pain and increases in scar elasticity were objectively
      assessable in all cases. In patients studied using Durometer and POSAS score,
      areas treated with autologous fat graft showed statistically significant
      reduction in hardness measurements in comparison with areas infiltrated with
      saline solution. POSAS scores showed a statistically significant reduction of a
      great deal of POSAS parameters as a result of an improvement of both clinical
      evaluation and patient perception. CONCLUSIONS: Injection of processed autologous
      fat seems to be a promising and effective therapeutic approach for scars with
      different origin such as burns and other trauma scars, and post-surgery and
      radiotherapy outcomes. In general, we can affirm that treated areas regain
      characteristics similar to normal skin, which are clinically objectivable,
      leading not only to aesthetic but also functional results.

PMID- 24036738
TI  - Superior eyelid crease approach for transobital neuroendoscopic surgery of the
      anterior cranial fossa.
AB  - Access to the anterior cranial fossa has traditionally required a large exposure
      of the surgical field, which can be a source of aesthetic and neurologic
      morbidity. Minimally invasive surgery approaches have been developed to overcome
      these adverse effects and was, for a long time, represented by endonasal
      endoscopic surgery. The superior eyelid crease approach of the anterior cranial
      fossa with supraorbital osteotomy was described in the early 80s as an
      interesting alternative to the endonasal approach. This keyhole endoscopic
      approach allows safe and efficient surgery of the orbit, the anterior cranial
      fossa, and the mesiotemporal lobe. We successfully treated 10 patients with
      benign tumors of the anterior cranial fossa, with excellent cosmetic results and
      no complications. This study presents the surgical technique and its potential
      indication and limits throughout our experience as well as a review of the
      literature. 

PMID- 24036739
TI  - Using methyl methacrylate in forehead contouring for aesthetic purposes.
AB  - Various methods using autologous bone grafts or alloplastic implants have been
      reported for the contouring of flat or depressed foreheads; the majority of these
      reports deal with correction of cranial deformities arising from injuries or
      congenital conditions. These methods all require relatively or quite invasive
      procedures. However, it is of course desirable if cosmetic surgery can be
      performed with minimally invasive procedures. The author presents an outpatient
      procedure using methyl methacrylate for aesthetic forehead contouring. From
      January 2006 to November 2012, 210 patients underwent methyl methacrylate
      forehead augmentation on an all outpatient basis. Under only local anesthesia, a
      V-shaped transverse scalp incision (5 cm length) was made behind the front hair
      line, followed by subperiosteal dissection of the skin covering the forehead.
      Methyl methacrylate was inserted and manually molded to the desired contour
      through the skin. The amount of methyl methacrylate used ranged from 10 to 40 mL,
      with a mean of 25 mL, depending on the size and shape. The follow-up period
      ranged from 3 months to 6 years, averaging 45 months, and with the exception of a
      very small percentage, all patients were satisfied with the results. Based on
      these results, the author concludes that aesthetic forehead augmentation using
      methyl methacrylate is an effective surgical procedure with minimal side effects
      and a high degree of patient satisfaction. 

PMID- 24036740
TI  - The effect of perforated punctal plugs in the management of acquired punctal
      stenosis.
AB  - OBJECTIVE: The objectives of this study were to report the success rates for
      perforated punctual plug (PPP) in the management of acquired punctual stenosis
      and to evaluate the factors influencing success rates. DESIGN: This was a
      retrospective, cross-sectional, comparative study. PARTICIPANTS: There were 20
      patients. METHODS: Twenty eyes of 20 patients who underwent PPP implantation for
      the management of acquired punctual stenosis and punctual obstruction were
      retrospectively evaluated regarding sex and age of the patients and the duration
      and severity of epiphora, associated blepharitis, and the success of treatment.
      In all patients, punctum dilation was performed carefully to prevent damage to
      the ampulla before the insertion of plugs. Perforated punctual plugs were removed
      2 months after insertion. RESULTS: There were 7 cases of punctal stenosis, 9
      cases of membranous obstruction, 2 punctal burns, 1 papilloma, and 1 nevus
      involving the punctum causing epiphora. The mean age of patients was 41.4 (SD,
      3.9) years. The mean interval between the onset of epiphora and PPP implantation
      was 32.1 (SD, 10.7) months. Associated chronic blepharitis was detected in 13
      eyes. Success was achieved in 17 eyes (85%). Patients whose procedures failed
      were older (67.7 vs 36.8, P = 0.019) and more likely to have blepharitis (100:
      23.5%, P = 0.031). Spontaneous plug loss was noted in 4 eyes between the 1- and 2
      month follow-up examination. No patients had residual epiphora. CONCLUSIONS:
      Perforated punctual plug implantation for the treatment of acquired punctual
      stenosis and obstruction is very effective. However, careful punctum dilation
      should be performed, and the patient age and comorbidities should be considered
      before treatment.

PMID- 24036741
TI  - Algorithm for reconstruction of composite cranial defects using the fascial
      component of free anterolateral thigh flaps.
AB  - BACKGROUND: In case of composite cranial defect including the dura mater, the
      cranial bone, and the scalp, the fascial component of the anterolateral thigh
      flap can be used for dural reconstruction. However, the advantages and
      applications of the fascial component depending on the type of defect have not
      been thoroughly discussed. We made the algorithm for reconstruction of composite
      cranial defects using the fascial component of free anterolateral thigh flaps.
      PATIENTS AND METHODS: Six cases of composite cranial defects were reconstructed
      using free anterolateral thigh flaps with the fascial component. The type of
      method used was classified into 3 types. Type 1 involves separating the fascia
      from the flap completely and using it as a nonvascularized component. In type 2,
      the fascia is not separated from the flap and is instead used as a vascularized
      component. Type 3 involves separating the vascularized adipofascial component
      from the skin paddle and using it as a chimeric pattern flap. The algorithm for
      determining the type of fascial component is applied depending on the condition
      of the defect. RESULTS: All flaps were transferred successfully in every case. In
      4 cases, the type 1 method was used. The type 2 and 3 methods were used in 1 case
      each. Cranial bone reconstruction was performed in 3 cases. There were no major
      complications after the procedures. CONCLUSIONS: The fascial component is useful
      for dural reconstruction. The type of fascial component used is selected
      depending on the condition of the defect.

PMID- 24036742
TI  - Study comparing midazolam and nitrous oxide in dental anxiety control.
AB  - The purpose of this study is to comparatively assess the effect of midazolam and
      nitrous oxide associated with oxygen, in lower third molar extractions, on the
      change in the anxiety level of patients by salivary cortisol dosage. Twenty-eight
      male patients underwent lower third molar extraction under sedation with
      midazolam and nitrous oxide. Objective (salivary cortisol dosage) and subjective
      (Corah Dental Anxiety Scale) data have been obtained. By salivary cortisol, 40
      minutes after midazolam administration, there has been a statistically
      significant difference compared with the mean baseline value. Midazolam was the
      most effective sedation method for reducing salivary cortisol level. 

PMID- 24036743
TI  - Facial plastic surgery area acquisition method based on point cloud mathematical
      model solution.
AB  - It is one of the hot research problems nowadays to find a quick and accurate
      method of acquiring the facial plastic surgery area to provide sufficient but
      irredundant autologous or in vitro skin source for covering extensive wound,
      trauma, and burnt area. At present, the acquisition of facial plastic surgery
      area mainly includes model laser scanning, point cloud data acquisition,
      pretreatment of point cloud data, three-dimensional model reconstruction, and
      computation of area. By using this method, the area can be computed accurately,
      but it is hard to control the random error, and it requires a comparatively
      longer computation period. In this article, a facial plastic surgery area
      acquisition method based on point cloud mathematical model solution is proposed.
      This method applies symmetric treatment to the point cloud based on the
      pretreatment of point cloud data, through which the comparison diagram color
      difference map of point cloud error before and after symmetry is obtained. The
      slicing mathematical model of facial plastic area is got through color difference
      map diagram. By solving the point cloud data in this area directly, the facial
      plastic area is acquired. The point cloud data are directly operated in this
      method, which can accurately and efficiently complete the surgery area
      computation. The result of the comparative analysis shows the method is effective
      in facial plastic surgery area. 

PMID- 24036744
TI  - Screw implantation in the globe: the risk of delayed hardware migration from
      craniofacial repair.
AB  - Plating system modification has enabled the use of rigid fixation in younger
      patients having maxillofacial surgery. One of the common reported complications
      of the use of plates and screws in children is screw migration due to skeletal
      maturation. Ophthalmic complications due to maxillofacial surgery reported to
      date include oculomotor and abducens palsies, lacrimal damage and vision loss due
      to infection, retrobulbar hemorrhage, and compartment syndrome. We describe a
      complication unique to screw migration resulting in orbital fixation and near
      globe rupture in a patient with Treacher Collins syndrome. We hope to alert our
      colleagues to the potential risk of screw and hardware migration and breakage,
      particularly in the setting of craniofacial surgery performed on a child before
      maturation of craniofacial osseous structures. 

PMID- 24036745
TI  - Backward distraction osteogenesis in a patient with severe mandibular
      micrognathia.
AB  - Maxillary skeletal prognathism can involve severe mandibular micrognathia with
      marked mandibular retrognathism or hypoplasia. For patients with such a
      condition, a conventional treatment is mandibular advancement by sagittal split
      ramus osteotomy (SSRO). This procedure has problems such as insufficient
      advancement, instability of jaw position, and postoperative relapse. Thus, in
      recent years, mandibular distraction osteogenesis has been used in some patients.
      Mandibular distraction has many advantages, but an ideal occlusion is difficult
      to achieve using this procedure. That is, 3-dimensional control cannot be
      attained using an internal device that is unidirectional. This report describes a
      case of severe mandibular micrognathia in a 14-year-old girl treated using
      backward distraction osteogenesis. This procedure was first reported by Ishii et
      al (Jpn J Jaw Deform 2004; 14:49) and involves a combination of SSRO and ramus
      distraction osteogenesis. In the present study, intermaxillary fixation in
      centric occlusion was performed after osteotomy, and proximal bone segments were
      distracted in a posterosuperior direction. This procedure is a superior surgical
      technique that avoids the drawbacks of SSRO and conventional mandibular
      distraction. However, it applies a large load to the temporomandibular joints and
      requires thorough management. Thus, careful evaluation needs to be made of the
      indication for backward distraction osteogenesis. 

PMID- 24036746
TI  - Numerical survey of the different shapes of human chin.
AB  - Experimental results are reported for the numerical quantities of the different
      shapes of human chin where, to the best of the author's knowledge, this approach
      has never been applied. The results are based on 3143 pictures of chins taken
      from the Internet of which 1328 were of women and 1815 of men. The author has
      succeeded to classify all the chins into 3 shapes: the cleft chin for men only,
      2.23% of the total; the double chin, 15.69% = 14.0% + 1.69%; and the normal chin,
      82.09% = 41.52% + 40.57%, where the first number is for men and the second for
      women. 

PMID- 24036747
TI  - Malignant tumors of the parotid gland in children: incidence and outcomes.
AB  - BACKGROUND: Population-based analysis of the incidence, demographics, and
      management outcomes in children with malignant tumors of the parotid gland.
      METHODS: Surveillance, Epidemiology, and End Results database (1973-2009) was
      researched for all patients younger than 20 years. RESULTS: Overall, 284 patients
      were identified. Annual incidence of these tumors was 1.43 cases per million. The
      highest incidence occurred in girls (0.86/1,000,000), black children
      (0.849/1,000,000), and adolescents (1.56/1,000,000). Median age at diagnosis was
      13.5 years. Most patients were 10 years or older (n = 256, 90%). Most patients
      presented with local disease (n = 207, 76%). Only 3% had metastasis at time of
      diagnosis. Most tumors were mucoepidermoid carcinomas (n = 139, 49%) or acinar
      cell carcinomas (n = 113, 40%). There were no differences in survival between
      mucoepidermoid and acinar cell carcinomas (96% vs 98% respectively, P = 0.317).
      Overall mortality was 4.6% over the study period. Overall survival was 96% at 5
      years, 95% at 10 years, and 83% at 20 years. Adolescents had significantly higher
      mortality rates (7.1% vs 1.6% for children <15 years of age, P = 0.23).
      Multivariate analysis identified the use of adjuvant radiation therapy (hazard
      ratio, 6.01; 95% confidence interval, 1.15-31.45; P = 0.034) as the only
      independent predictor of poor outcome. CONCLUSIONS: Malignant parotid gland
      tumors are most common in adolescents, and this subgroup has worse outcomes. The
      role of radiotherapy remains controversial.

PMID- 24036748
TI  - Normocephalic pancraniosynostosis.
AB  - Normocephalic pancraniosynostosis is a rare variant of craniosynostosis
      associated with delayed presentation and elevated intracranial pressure. We
      present 2 cases of normocephalic pancraniosynostosis highlighting the common
      clinical course, radiographic findings, and intraoperative findings seen in
      children with normocephalic pancraniosynostosis. 

PMID- 24036749
TI  - Operative treatment of huge adult frontal nasoethmoid meningoencephalocele.
AB  - A retrospective study was undertaken in order to choose the operative methods of
      adult huge frontal nasoethmoid meningoencephalocele. Ten patients were admitted
      to hospital for their craniofacial mass. Of these, 9 cases suffered meningocele
      and 1 case meningoencephalocele. Four cases undertook the mass resection and
      repairing operation with postoperative lumbar drainage; at final, they had to
      receive shunt operation. Six cases underwent mass resection and repairing
      operation with shunt surgery at one stage; they recovered smoothly. Our results
      suggest that the adult patients with huge meningoencephalocele have larger
      subarachnoid cavity. When they receive repairing operation, their subarachnoid
      cavity would be decreased in volume and cerebrospinal fluid (CSF) circulation
      could be disturbed. In order to maintain the balance of CSF production and
      absorption, the shunt operation should be given at the same stage. 

PMID- 24036750
TI  - Reconstruction of singular eyelid defects in aging individuals based on facial
      aesthetic subunits.
AB  - BACKGROUND: In consideration of the distinctive structural characteristics of the
      eyelid, the optimally matching donor site to the original recipient site skin
      should be selected when a full-thickness skin graft is anticipated in a small
      sized or medium-sized eyelid defect in middle-aged or elderly patients. METHODS:
      Eight patients ranging in age from 47 to 71 years suffered singular eyelid
      defects of different causes. Based on the location, shape, and degree of the
      defects, we removed the redundant skin as a skin graft from the same side in the
      contralateral eyelid in a routine blepharoplasty procedure and transferred the
      graft to repair the defect. RESULTS: The skin grafts survived in all cases, and
      the incisions healed primarily. The eyelid laxity improved, and no complications
      occurred. All cases were followed up for 3 months to 2 years, the quality of skin
      grafts was similar to that of the surrounding skin, and the activity was ideal.
      CONCLUSIONS: When an eyelid defect is not amenable to direct closure and skin
      grafting is selected, the proper donor site is vital to the final outcome. The
      same facial aesthetic subunits, such as sufficient laxity in the contralateral
      eyelid skin in middle-aged and elderly patients, can provide the best match with
      the recipient skin and represent the best donor site for defect reconstruction.

PMID- 24036751
TI  - Mixed infection of an atypical Mycobacterium and Aspergillus following a
      cryopreserved fat graft to a face.
AB  - We report a chronic infection of a patient who received a cryopreserved fat graft
      on her face. A 22-year-old female patient presented with multiple abscesses of
      her face. Four months previously, she received a second fat graft with the fat
      harvested at a previous surgery which was cryopreserved for 2 months. On
      examination, she had tender erythematous nodules on both cheeks. A computed
      tomography of her neck showed multiple peripheral enhancing nodular lesions. In
      an open pus fungus culture, Aspergillus fumigatus growth was observed. On the
      Mycobacterium Other Than Tuberculosis identification PCR, Mycobacterium fortuitum
      was found. She was treated with levofloxacin, clarithromycin, and minocycline for
      11 months, and finally the symptoms subsided. To avoid infection after the fat
      graft, cryopreserved fat should not be used as a possible grafting material. In
      cases of persistent infection, or in cases of waxes and gains after drainage of
      pus and short-term antibiotics therapy, atypical Mycobacterium or Aspergillus
      should be suspected and a PCR for them should be carried out. 

PMID- 24036752
TI  - Maxillary growth after the use of protraction head gear in conjunction with
      presurgical orthopedics and gingivoperiosteoplasty for complete bilateral cleft
      lip and alveolus patients.
AB  - INTRODUCTION: Maxillary development is often inadequate in bilateral cleft
      patients. The use of presurgical orthopedics (PSO) and gingivoperiosteoplasty
      (GPP) may promote bone formation at the alveolar cleft, but can also have
      detrimental effects on maxillary development. Our objective was to investigate
      the effect of PSO and GPP on maxillary development in bilateral cleft lip and
      alveolus (BCLA) patients. SUBJECTS AND METHODS: We had 3 complete BCLA patients
      who had received PSO. All patients underwent cheiloplasty and GPP simultaneously.
      At 4 years, maxillary protraction head gear was used as part of the protocol.
      They were evaluated by cephalometric analysis at 4 and 8 years of age, and by CT
      imaging at 5 years of age. RESULTS: At 4 years of age, patients with all BCLA had
      anterior crossbite of deciduous central incisors. As a result of maxillary
      protraction, jaw development at 8 years was good. Among all patients, only one
      showed bone formation at the alveolar cleft sufficient to avoid alveolar bone
      grafting (ABG). DISCUSSION: All patients presented anterior crossbite in the
      premaxillary region, but had good maxillary growth at 8 years old as a result of
      maxillary protraction. The combination of PSO and GPP can potentially eliminate
      the need for ABG and does not significantly retard maxillary development. PSO
      with GPP and protraction head gear may be an option, but long-term growth is not
      known.

PMID- 24036753
TI  - Persisting subcutaneous emphysema of eyelids mimicking orbital tumor.
AB  - Eyelids emphysema is a rare condition due to air trapping in subcutaneous tissue
      of the orbit. It has been clinically and radiologically documented, but
      histologic evaluation has not been noted. We report a case of a middle-aged woman
      with periorbital swelling due to self-induced Valsalva maneuver, persisting after
      decompressive therapy. A fine-needle biopsy was performed and showed a mixed
      population of osteoclastic-like giant cells and mononuclear epithelioid cells,
      which were suspected of pathological proliferative disease. Specimens from
      blepharoplasty indicated pseudocystic empty spaces surrounded by epithelioid
      cells and giant cell granulomas. Immunohistochemical stains favored diagnosis of
      benign granulomatous disease, such as subcutis cystic pneumatosis. Histologic
      examination represented an important tool for differential diagnosis with soft
      tissue neoplasms of the orbit in subcutis emphysema with unusual clinical
      presentation and abnormal course. 

PMID- 24036754
TI  - Impact of corrective rhinologic surgery on rhinogenic headache.
AB  - OBJECTIVE: In this study, the localization of the headache, mucosal contact
      points, sinonasal anatomic variations and the incidence of mucosal abnormalities
      were determined in patients with rhinogenic headache, and the efficacy of the
      corrective surgery on the severity of the headache and the rate of improvement on
      that localization were investigated. STUDY DESIGN: Conducted in a prospective
      manner. LEVEL OF EVIDENCE: Level 2b. METHODS: Sixty-five patients who were
      admitted with sinonasal symptoms and headache and had septoplasty, endoscopic
      sinus surgery, or surgical procedures involving the nasal turbinates were
      included in this study. The quality and the severity of the headache were
      investigated preoperatively as well as in the 3rd and 12th postoperative months.
      RESULTS: Headache was most frequently localized the frontal region. The mucosal
      contact points were most frequently localized between the nasal septum and the
      middle or inferior turbinates. Differences between preoperative headache and
      headache in postoperative 3rd month and postoperative 12th month were
      statistically significant (P < 0.05). Improvement in headache after surgery was
      statistically significant in cases with Haller cell and paradoxical middle
      turbinate and in patients with contact points between the nasal septum and the
      middle or inferior turbinates (P < 0.05). CONCLUSIONS: We have shown the
      importance of surgery in the treatment of rhinogenic headache. We have also shown
      the reliability of the decongestion test for determining the indication for
      surgery. We suggest that the rhinologic surgery may have a great contribution to
      the treatment of headache.

PMID- 24036755
TI  - Measurement of fracture size using the picture archiving communication system in
      an outpatient clinic for factors that influence postoperative enophthalmos in
      adult inferior orbital wall fractures.
AB  - PURPOSE: This study aims to determine the relationships between postoperative
      enophthalmos, preoperative enophthalmos, and fracture sizes in adults with
      inferior orbital wall fractures. METHODS: The records of 31 patients who had
      operations for pure orbital floor blowout fractures from March 2003 to February
      2004 were retrospectively reviewed. Using the Picture Archiving Communication
      System, we measured fracture sizes according to the orbital computed tomography
      results. We calculated fracture sizes according to the supposition that the
      fracture was a 2-dimensional figure. Hertel exophthalmometry was performed on
      preoperative day 1 and 3 months postoperatively. RESULTS: Mean changes of
      enophthalmos were 2.80 mm (P < 0.05, paired t test). The mean fracture size was
      6.11 cm(2) (range, 3.56-11.73 cm(2)). Fracture size was a more accurate predictor
      of postoperative enophthalmos than the degree of preoperative enophthalmos
      (Pearson correlation; with preoperative enophthalmos = 0.513, with fracture size
      = 0.743, P < 0.05). In linear regression analysis, preoperative exophthalmometry
      measurements contributed approximately 27.1% to postoperative enophthalmos,
      whereas fracture size contributed approximately 54.3% (P < 0.05). In multiple
      regression analysis, the equation was Y = 0.313X + 0.464X' - 0.684 (X is the size
      of fracture; X', preoperative exophthalmometry measurement). The above 2 factors
      explained 82.3% of the total postoperative enophthalmos variance. Other factors,
      which contribute approximately 18%, might include time between insult and
      corrective surgery. CONCLUSIONS: In our study, fracture size was a better
      predictive factor for postoperative enophthalmos than preoperative
      exophthalmometric measurement. With our method, postoperative enophthalmos can be
      predicted more conveniently in a clinical setting, and decisions regarding the
      timing of early surgical reduction were made easier.

PMID- 24036756
TI  - Prevalence of dental anomalies in patients with cleft lip and palate.
AB  - The aim of the present study was to investigate the prevalence of dental
      anomalies in a group of patients with cleft lip and palate (CL/P) in the
      northeast of Iran. Ninety-one patients referring to the Cleft Lip and Palate
      Clinic of Mashhad Dental School were enrolled and classified into right CL/P,
      left CL/P, and bilateral CL/P groups. Photographs, dental casts, and panoramic
      and periapical radiographs were retrieved, and dental anomalies were recorded.
      chi test was used to analyze the frequency of dental anomalies according to type
      of cleft and sex. Missing maxillary lateral incisors was the most frequent dental
      anomaly, which was slightly higher in the bilateral group (61.1%). There were
      significantly more cases of missing lateral incisors outside the cleft area in
      right CL/P (P = 0.015). Peg lateral incisors were observed in 33.3% of bilateral
      CL/P compared with 28% of right and 23.3% of left unilateral cases. The sample
      presented rotations of central incisors in the cleft area in 33.3% of bilateral
      clefts. In unilateral clefts, it occurred more frequently in the right side
      (48%). Sexual dimorphism appeared only for maxillary central incisor rotation in
      the cleft area, which showed significantly greater frequency in females (P =
      0.025). Transposition of maxillary canine and first premolars was found in 5.5%
      of bilateral, 8% of right, and 3.3% of left unilateral clefts. The prevalence of
      dental anomalies in the studied sample seems to be higher than that reported in
      the normal population. More anomalies were observed at the cleft side. The
      frequency of most anomalies was not significantly different between the 2 sexes. 

PMID- 24036757
TI  - Predicting the outcome of microvascular decompression for primary trigeminal
      neuralgia by the use of magnetic resonance tomographic angiography.
AB  - BACKGROUND: Microvascular decompression (MVD) has been the available method to
      cure trigeminal neuralgia (TN), and several factors have been discussed as
      significant predictors of excellent outcome after MVD. OBJECTIVE: This study
      aimed to find out the value of magnetic resonance tomographic angiography (MRTA)
      in predicting the outcome of MVD for TNs. METHOD: A total of 157 cases of TNs who
      underwent MVD have taken MRTA preoperatively and postoperatively and then were
      followed up for 5 years. The possible prognostic factors were analyzed by chi(2)
      test and Kaplan-Meier survival analysis. RESULT: Five years after MVD, 83.4% (131
      cases) gave excellent, 10.2% (16 cases) gave good, and 6.4% (10 cases) gave poor
      results. A significant difference was found between the severity of postoperative
      neurovascular compression (chi(2) = 16.307, P < 0.01)/the relief rate of
      neurovascular compression (NVC) (chi(2) = 17.221, P < 0.01) and the outcome after
      MVD. However, no significant correlation was found between the severity of
      preoperative NVC and the outcome (chi(2) = 6.275, P = 0.329). The Kaplan-Meier
      survival curves showed that lower degree of postoperative NVC severity group and
      higher relief rate group had better pain relief after MVD. CONCLUSIONS:
      Postoperative MRTA can help us predict the outcome of MVD; less severity of
      postoperative NVC and more relief of compression could be possible prognostic
      factors.

PMID- 24036758
TI  - Traumatic dislocation of the mandibular condyle into the middle cranial fossa in
      an elderly patient.
AB  - Dislocation of the mandibular condyle into the middle cranial fossa is a rare
      traumatic injury caused by transmission of upward force through the condyle onto
      the glenoid fossa resulting in fracture of the fossa and superior displacement of
      the condylar head. This type of injury occurs when the "safety mechanisms" of the
      mandible fail or are absent. The authors present the case of a 72-year-old female
      patient with multiple comorbidities who suffered a subcondylar fracture of the
      left mandible and dislocation of the right mandibular condyle into the middle
      cranial fossa after a fall. Bilateral external fixation of the mandible to the
      zygomatic arch was utilized to minimize operative time and provide definitive
      treatment. Many factors must be taken into account when determining the treatment
      modality for this type of injury, and the final decision should be tailored to
      each individual case based on several factors including the length of time
      between injury and presentation, concomitant neurologic deficit, age, and
      stability of the patient. The goals of treatment are reduction of the
      dislocation, avoidance of neurologic injury, and restoration of mandibular
      function. A multidisciplinary effort is necessary to optimize patient care. 

PMID- 24036759
TI  - Management of orbital complications of sinusitis in pediatric patients.
AB  - The most common reason of orbital infections is sinusitis. Orbital complications
      of sinusitis are mostly seen in children. Loss of vision and intracranial
      infections are among the complications of sinusitis. Prompt diagnosis and
      treatment is very important in the management of orbital complications. The
      orbital complication can be in the form of cellulitis or abscess. A retrospective
      review of 26 pediatric patients with orbital complications due to sinusitis was
      presented in this study. Of 26 patients, there were 13 cases of preseptal
      cellulitis, 2 cases of orbital cellulitis, and 11 cases of subperiosteal abscess.
      We grouped the preseptal and orbital cellulites in one category and the
      subperiosteal abscess in the other. All patients in the cellulitis group
      recovered by medical treatment. All the patients were treated by surgical
      drainage. Early diagnosis and appropriate treatment method are vital for the
      treatment of orbital complications secondary to sinusitis. 

PMID- 24036760
TI  - Severe bone resorption in expanded polytetrafluoroethylene chin augmentation.
AB  - Expanded polytetrafluoroethylene implant is usually considered as a wonderful
      implant for chin cosmetic augmentation with no or less bone resorption compared
      with solid silicone implant. However, one severe bony erosion in expanded
      polytetrafluoroethylene chin augmentation was found in our clinical work. We
      consider that the possible reason about severe bone resorption in such situation
      is most relative to the mentalis muscle hyperactivity, rather than the kinds of
      materials. We also strongly advise that genioplasty is suitable for the cases
      with mentalis muscle hyperactivity caused by a dentofacial deformity. 

PMID- 24036761
TI  - Dolichocephaly without sagittal craniosynostosis.
AB  - Premature closure of the sagittal suture is thought to be fundamental to the
      etiopathology for the disease process called sagittal craniosynostosis. This
      process traditionally results in a well-known skull malformation termed
      dolichocephaly. Over recent decades, some authors have questioned the suture as
      the primary driving force for this pathology. This is a retrospective cases
      series of 4 patients from 2011 to 2012 who presented to the Yale Craniofacial
      Clinic for evaluation of dolichocephaly. The 4 children, 3 boys and 1 girl, had
      physical examinations and cranial indices concerning for sagittal
      craniosynostosis; however, subsequent computed tomographic imaging revealed
      sagittal suture patency. This series adds to a growing body of literature, which
      describes abnormal head shapes not attributable to overt suture pathology. 

PMID- 24036762
TI  - Postintubation laryngotracheal stenosis: assessing the success of surgery.
AB  - OBJECTIVE: This study evaluated the outcome in adult patients with
      laryngotracheal stenosis (LTS) and assessed the effect of procedures on their
      quality-of-life scores. METHODS: The study included 15 adult patients with LTS
      (11 males [73.3%], 4 females [26.7%]; mean age, 32 years [range, 10-52 years])
      treated at the Department of Otolaryngology Head and Surgery Clinic, Izmir
      Ataturk Research Hospital, Turkey, from 1997 to 2008. Success of the surgery is
      evaluated by decanullation rate, Short form-36 (SF-36), and the Medical Research
      Council dyspnea scale. RESULTS: The etiology of the LTS was intubation related in
      14 cases (93.3%) and idiopathic in 1 case. According to the Myers-Cotton
      classification, 2 (13%), 8 (54%), and 5 (33%) patients were at stages 2 to 4,
      respectively. Fourteen patients had a mean follow-up of 57 months (range, 24-256
      months). The stenotic segment involved 1 to 3 cm (mean, 1.7 cm) of trachea, and 2
      to 5 tracheal rings (mean, 3.1) were resected. Postoperative decannulation was
      achieved in 13 patients (86.6%). In the short form-36 questionnaire, all of the
      parameters except for "role-emotional" were found to be significant (P < 0.01).
      The Medical Research Council dyspnea scale assessment revealed a significant (P <
      0.001) decrease postoperatively. CONCLUSIONS: Segmental resection with primary
      anastomosis is an effective method and can be used as the first option in
      selected cases of advanced stenosis.

PMID- 24036763
TI  - Preoperative velopharyngeal morphology in older cleft palate patients with
      postoperative velopharyngeal closure versus velopharyngeal insufficiency.
AB  - The purpose of this study was to investigate the preoperative morphology of
      velopharyngeal structures in older patients with cleft palate and to evaluate
      which structure(s) could distinguish velopharyngeal function. The investigators
      implemented a retrospective study and 66 patients whose palate was repaired by 1
      surgeon with the same technique were selected, including 38 boys and 28 girls,
      aged from 5 years and 1 month to 28 years and 6 months. All these patients were
      taken lateral preoperative cephalograms at rest and during phonation of /i/.
      Fifteen lengths, 3 ratios, and 1 angle variable were defined in this study. The
      follow-up time was from 3 months to 12 months. All these measurements were
      analyzed by independent samples t test and discriminant analysis in a stepwise
      method, while P value was set at 0.05. In this study, there were 30 patients with
      velopharyngeal closure (VPC) and 36 patients with velopharyngeal insufficiency
      (VPI) after surgery. Differences in velar length, posterior velar length,
      pharyngeal height, hard-soft palatal angle, and pharyngeal height-depth ratio
      were significantly different at rest, while all the measurements during phonation
      were not significantly different. Discriminant analysis showed that the VPC group
      could be discriminated from the VPI group primarily on the basis of velar length,
      pharyngeal depth, and VP ratio, of which the correlation ratio was 0.963 and the
      discriminant rate was 100%. Therefore, the results suggested not only velar
      length and pharyngeal depth but also pharyngeal height significantly affected the
      formation of normal velopharyngeal function. Furthermore, there was a strong
      prognostic significance of preoperative velar length, pharyngeal depth, and VP
      ratio for postoperative velopharyngeal function. 

PMID- 24036764
TI  - A rare tumor of the parapharyngeal space: angiomyxolipoma.
AB  - Parapharyngeal space tumors are uncommon, most are salivary gland tumors (50%),
      and they are often pleomorphic adenomas. Neurogenic tumors are the second most
      common primary tumors of all neoplasms in the parapharyngeal space (30%).
      Angiomyxolipoma is a very rare form of lipoma. Up until now, only 12 cases
      located on different sides of the body were reported. Presented here is a case
      report of a patient with an angiomyxolipoma of the parapharyngeal space. A 17
      year-old boy had a slowly growing, painless mass on the left side of the neck.
      During the oropharyngeal examination, medial displacement of the left tonsilla
      palatina was observed. Magnetic resonance imaging findings were of a 6 * 5.5 * 3
      cm "dumbbell"-shaped parapharyngeal mass. A fine needle aspiration of the mass
      showed no specific histopathology. The patient underwent a transparotid
      transcervical approach for the excision of the tumoral mass under general
      anesthesia. Although an angiomyxolipoma is a rare form of lipoma, it is a
      pathology that should be kept in mind for the differential diagnosis of
      parapharyngeal tumors. 

PMID- 24036765
TI  - The effect of corticosteroid against streptomycin ototoxicity.
AB  - The aim of this experimental study was to determine the possible protective role
      of corticosteroid in prevention of streptomycin-induced ototoxicity. Twenty-eight
      adult Wistar albino rats were divided into 4 groups: control (n = 7),
      streptomycin (n = 7), corticosteroid (n = 7), and streptomycin + corticosteroid
      (n = 7). Rats were tested with distortion product otoacoustic emissions (DPOAEs)
      in the beginning and at the end of the study. The animals in all groups were
      killed under general anesthesia on the 45th day after the last DPOAE
      measurements. Hearing results were analyzed statistically to determine
      differences in amplitudes of DPOAE. In addition, the cochleas of each rat were
      evaluated by histopathologic and immunohistochemical examination. Significant
      difference was not observed in cochlear hair cells in the control and
      corticosteroid groups, whereas severe degeneration of hair cells and increased
      apoptotic cells were observed in the streptomycin group. Moderate degeneration
      was observed in the streptomycin + corticosteroid group. The hair cells were
      partially intact. DP-gram of the streptomycin and streptomycin + corticosteroid
      groups was significantly deteriorated (P < 0.05). The coadministration of
      steroids with streptomycin, which has a serious ototoxic effect, did not lead to
      a limitation of this harmful effect. 

PMID- 24036766
TI  - Rejuvenation surgery through blepharoplasty incision for mild to moderate upper
      eyelid sagging in older Asian patients.
AB  - OBJECTIVES: The objective of this study was to evaluate the clinical outcome of
      rejuvenation surgery through double eyelid incision instead of face-lifting for
      the correction of different types of the upper eyelid sagging in older East Asian
      patients. MATERIALS AND METHODS: A total of 40 patients (80 aging upper eyelids)
      with upper eyelid sagging were retrospectively examined. The age of the patients
      ranged from 53 to 85 years (mean age, 65 y). After a thorough preoperative
      evaluation, the corresponding operations were performed and the follow-up results
      were obtained. RESULTS: The operation of each patient with a mean follow-up
      period of 6 months was combined for a total of 80 rejuvenation operations. A
      total of 34 patients (85%) were satisfied with the postoperative appearance, 3
      patients (7.5%) showed inadequate skin reduction, 1 patient (2.5%) had asymmetry
      between 2 blepharoplasty lines, and 2 patients (5%) showed obvious scars.
      CONCLUSIONS: Through a thorough preoperative evaluation, rejuvenation surgery
      through blepharoplasty incision is an effective solution for mild to moderate
      upper eyelid sagging in older Asian patients.

PMID- 24036767
TI  - Repair of cocaine-related oronasal fistula with forearm radial free flap.
AB  - BACKGROUND: Cocaine snorting may cause significant local ischemic necrosis and
      the destruction of nasal and midfacial bones and soft tissues, leading to the
      development of a syndrome called cocaine-induced midline destructive lesion. A
      review of the English-language literature reveals only a few articles describing
      the treatment of hard and/or soft palatal perforation related to cocaine
      inhalation. Described here are 4 patients with a history of cocaine abuse showing
      palatal lesions. MATERIALS AND METHODS: From 2010 to 2013, a total of 4 patients
      affected by cocaine-related midline destructive lesions were referred to our
      department. They all presented signs of a cocaine-induced midline destructive
      lesion. They showed wide midfacial destruction involving the nasal septum as well
      as the hard and soft palates causing an ample oronasal communication. RESULTS: In
      3 patients, oronasal communication has been treated successfully using a personal
      technique based on a partially de-epithelialized forearm free flap. The fourth
      patient had been treated only with local debridement because, when she came to
      our attention, her abusive habits were still unsolved. DISCUSSION: Different
      surgical options have been reported such as local, regional, and free flaps for
      hard and soft palate reconstruction. However, because of an unpredictable
      vascularization of the palatal tissues and owing to the scarceness of the local
      soft tissues, local flaps are at high risk for partial and complete failure. The
      transfer of free vascularized tissue, however, seems to be the most reliable and
      logical solution for medium- to large-sized fistulas. Among the various free
      flaps, we choose the radial forearm type because of the pedicle length and the
      flap thickness.

PMID- 24036768
TI  - Vastus lateralis muscle flaps for monitoring buried anterolateral thigh flaps.
AB  - Postoperative monitoring of buried anterolateral thigh flaps is difficult with
      standard methods. Although a monitoring skin flap based on a second cutaneous
      perforator is often used, it requires tedious dissection of 2 sets of perforators
      and cannot be used when a second perforator is absent. We present 2 patients who
      underwent head and neck reconstruction with buried anterolateral thigh flaps,
      which were monitored with a small, externalized segment of the vastus lateralis
      muscle accompanying the main skin island. Both flaps survived, and the monitoring
      muscle flaps remained pink throughout the postoperative period until removal. For
      monitoring, a vastus lateralis muscle flap has several advantages over a skin
      flap. This method obviates the need for dissecting a second cutaneous perforator
      and allows reliable monitoring regardless of the number of available cutaneous
      perforators. We believe this method is a versatile option for monitoring buried
      anterolateral thigh flaps. 

PMID- 24036769
TI  - Midterm clinical and tomodensitometric evaluation of cortical bone repair using
      bone substitute and allogenic membrane protection in the areas of cortical bone
      harvesting in the parietal cranium in preimplant reconstructive surgery.
AB  - The authors present their clinical and computed tomographic findings in a series
      of 13 cases of monocortical bone harvesting, in the setting of preimplant
      reconstructive surgery, with the harvest sites filled with granular bovine bone
      substitute, which had an additional coverage using a collagen membrane. These
      patients were compared with a control group of 6 patients who had not received
      any cranial bone reconstruction during the initial harvesting. Clinical and
      computed tomographic evaluations of the repaired parietal cortical bone harvest
      sites were performed to study the contour of the cortical bone harvest sites in
      relation to the surrounding soft tissue. Among the 13, there were no clinical
      cases of infection or allergic reaction. Midterm results of the parietal cortical
      bone reconstruction using granular bone substitute with overlying protective
      biodegradable membrane show that this method of reconstruction of the cranium
      after cranial bone harvesting resulted in significantly improved clinical
      outcomes. 

PMID- 24036770
TI  - A new transnasal approach to nasolabial cyst: endoscopic excision of nasolabial
      cyst.
AB  - Nasolabial cyst (NC) is one of the midface lesions that are seen rarely.
      Nasolabial cyst is generally seen in females typically on the fourth and fifth
      decades and localized unilaterally. Diagnosis usually depends on clinical
      evaluation. Sublabial excision is the classic method, but endoscopic
      marsupialization is suggested in current literature. An NC that is totally
      excised endoscopically is introduced in this article. This is the first case of
      NC excised endoscopically that is described in English literature. 

PMID- 24036771
TI  - Piezoelectric decortication applied in periodontally accelerated osteogenic
      orthodontics.
AB  - Our aim was to evaluate the application of piezoelectric decortication in
      periodontally accelerated osteogenic orthodontics (PAOO). One hundred fifty-six
      patients with severe skeletal malocclusions were enrolled in this study.
      Ultrasonic decortications were performed in 187 labial or lingual PAOO of the
      maxillary and mandibular anterior teeth. Orthodontic decompensation started from
      the fifth day after operation. All patients healed uneventfully and no severe
      periodontic complications were recorded. Rapid teeth movement and relatively
      short treatment duration were realized. Alveolar fenestration and bony dehiscence
      was successfully addressed. With physical and mechanical properties of absence of
      macrovibration, ease of use and control, piezosurgery showed its great values in
      PAOO. 

PMID- 24036772
TI  - Treatment of hemimasticatory spasm with microvascular decompression.
AB  - Hemimasticatory spasm is a rare disorder characterized by paroxysmal involuntary
      contraction of the jaw-closing muscles. As the ideology and pathogenesis of the
      disease are still unclear, there has been no treatment that could give rise to a
      good outcome so far. Herein, we tried to use surgical management to cure the
      disease. Six patients with the disease were included in this study. These
      patients underwent microvascular decompression of the motor fibers of the
      trigeminal root. After the operation, all faces of the patients felt relaxed at
      varied degrees, except for 1 patient. Our study showed that microvascular
      decompression of the trigeminal nerve could lead to a better outcome. However, a
      control study with a large sample is needed before this technique is widely used.

PMID- 24036773
TI  - A porcine rib cartilage model for practicing ear-framework fabrication.
AB  - Surgical training models should be readily available to enable practice in vitro
      until the trainee is comfortable with the procedure. It is also important that
      the anatomy of the training model sufficiently resembles that of humans. Here, we
      present our model for training surgeons to fabricate costal cartilage for total
      ear reconstruction, using porcine rib cartilage. Pig ribs are very familiar and
      available at grocery stores at a low cost. The greatest advantage of this
      training model is the realistic anatomy and tactile nature similar to that of
      human cartilage. Using this training model, trainees could learn how to fabricate
      an auricular framework that is stable and aesthetically pleasing. 

PMID- 24036774
TI  - Augmentation rhinoplasty using a folded "pure" dermal graft.
AB  - BACKGROUND: Although there are several reports about the use of dermal or
      dermofat grafts, there are only a few reports about augmentation rhinoplasty
      performed using a "pure" dermal graft. Authors introduce the refined techniques,
      clinical experience, and report an aesthetically pleasing result of augmentation
      rhinoplasty performed using a folded pure dermal graft. MATERIALS AND METHODS:
      Between 2008 and 2012, augmentation rhinoplasty was performed in 68 cases using a
      folded pure dermal graft. Pure dermal graft was harvested from one side of the
      buttock close to the intergluteal crease and the graft length was approximately 7
      8 cm and the graft width was 1.5-2 cm, and the epidermis and fat were completely
      removed. Tip-plasty was performed using a conchal or septal cartilage as a
      columellar strut and an onlay graft. Pure dermal grafts are folded into 2 layers
      and sculpted to the desired size and shape, and are inserted into the
      supraperiosteal pocket. Ultrasonography was performed to know the absorption rate
      of the folded pure dermal grafts. RESULTS: The thickness of a dermal graft at
      postoperative 12 months was 60.3% of that at postoperative 1 month. Even with
      39.7% of reduction in the thickness of the dermal graft, the height of nasal
      dorsum after postoperative 1 year is considered to be well maintained. Among the
      68 cases that underwent augmentation rhinoplasty (43 primary and 25 secondary),
      most of the patients sustained consistent cosmetic results; however, 12 patients
      (17 %) showed over-absorption, under-absorption or contour irregularity of the
      dermal graft, and slight erythema. There were no aesthetically or medically
      serious problems needing secondary rhinoplasty such as hematoma formation,
      warping of the graft, graft extrusion, infection, and rejection of the graft.
      DISCUSSION: Augmentation rhinoplasty using a folded pure dermal graft has many
      advantages and is a very useful surgical option in patients who have an aversion
      to the use of artificial implants, who want to change the postoperative
      appearance of their nose due to insertion of an artificial implant into a more
      natural appearance, and when there is too much thinning of the skin due to
      repeated insertion of silicone implants.

PMID- 24036775
TI  - Piezosurgery versus conventional osteotomy in orthognathic surgery: a paradigm
      shift in treatment.
AB  - The aim of the study was to compare in a randomized controlled clinical trial the
      use of the piezoelectric osteotomy as an alternative to the conventional approach
      in terms of surgery time, intraoperative blood loss, cut quality, nerve injury,
      and costs.One hundred ten patients who had orthognathic surgery procedures with
      bimaxillary osteotomy were divided into 2 groups: group A was treated with a
      piezosurgery device, and group B, with a reciprocating saw and bur.The
      piezosurgical bone osteotomy permitted individualized cut designs. The surgical
      time in group A was reduced, with a mean for the mandibular osteotomy (1 side)
      between 3 minutes 31 seconds and 5 minutes 2 seconds, whereas in group B, the
      surgical time was between 7 minutes 23 seconds and 10 minutes 22 seconds. The
      surgical time in group A for the Le Fort I osteotomy was between 5 minutes 17
      seconds and 7 minutes 55 seconds in group A and between 8 minutes 38 seconds and
      15 minutes 11 seconds in group B. All patients in group A had a low blood loss
      (<300 mL) versus patients of group B who had a medium to high blood loss (medium
      loss: 400 mL, high loss: >500 mL). Inferior alveolar nerve sensation was retained
      in 98.2% of group A versus 92.7% in group B at 6 months postoperative
      testing.Piezoelectric osteotomy reduced surgical time, blood loss, and inferior
      alveolar nerve injury in bimaxillary osteotomy. Absence of macrovibrations makes
      the instrument more manageable and easy to use and allows greater intraoperative
      control with higher safety in cutting in difficult anatomical regions. 

PMID- 24036776
TI  - Inner cyst approach, remove bronchial cervical cyst.
AB  - Although most cystic lesions in young adults represent a branchial cleft cyst,
      the bronchial cervical cyst is not rare (Acta Oto-Laryngologica 2010;130:300).
      Surgical excision is both diagnostic and curative and also eliminates the risk of
      infection or recurrence. As we have all known, it is hard to protect some
      important structures in an inflamed tissue, especially in infants. However, a
      correct approach can avoid this kind of iatrogenic injury. An accurate diagnosis
      is always by pathologic examination. The diagnosis can be made before operation
      when finding cartilage in the nodule. We present the preoperative diagnosis by
      finding gas in the nodule and removed it by inner cyst approach without
      surrounding tissue injury. 

PMID- 24036777
TI  - Modified triaca-style wing osteotomy to correct facial asymmetry in a patient
      with horizontal growth-type condylar hyperplasia.
AB  - In this short communication, we suggest a slight modification of Albino Triaca's
      chin-wing osteotomy to vertically correct the inferior border of the mandible in
      a patient with horizontal growth-type facial asymmetry due to condylar
      hyperplasia. 

PMID- 24036778
TI  - Influence of vascular twisting on the supermicroanastomosis of superficial
      inferior epigastric artery.
AB  - Arterial microanastomoses with small-caliber vessels, such as those with an
      internal diameter less than 0.2 mm, are susceptible to inadvertent twisting. A
      total of 20 supermicroanastomoses were performed in the superficial inferior
      epigastric artery (SIEA)-based flap model of ten 10-week old, 300- to 350-g male
      Sprague-Dawley rats. Two rats with 4 flaps comprised each experimental group: a
      negative control, a control with end-to-end SIEA arterial supermicroanastomosis,
      and 3 experimental groups (EAs), such as EA1, 2, and 3 with 90-, 180-, and 270
      degree twisting supermicroanastomosis, respectively. Each SIEA was clamped with a
      Superfine Vascular Clamp (S&T Co, Neuhausen, Switzerland) and anastomosed with 6
      stitches. On postoperative day 10, the skin flap surface texture had no color
      change, and skin necrosis was not found in any group within a 1.0-mm grid
      measurement in less than 1% of the whole skin flap surfaces. There were
      statistically significant differences between the groups in 4 criteria, such as
      cellular swelling, nuclear pleomorphism, nuclear swelling, and microvessel
      numbers. The pulsatility index was increased in the EA1 and EA2 on postoperative
      days 1 and 2, showing decrease in the similar preoperative value on postoperative
      day 10, but decreased pulsatility index was continuous in the EA3 during the
      postoperative day 10. The resistance index was significantly different between
      preoperative and postoperative day 10 especially in the EA2 and EA3.
      Ultramicroscopic findings in the EA3 group showed an increase in tunica media
      necrosis, convolution of the internal elastic lamina, and densely packed
      platelets, fibrins, and erythrocytes. 

PMID- 24036779
TI  - Medpor implant fixation using fibrin glue in blowout fracture surgery.
AB  - The Medpor implant is (Prous polyethylene, Porex Surgical Inc, Newnan, GA, USA)
      widely used to reconstruct orbital wall defects. However, this implant is
      commonly associated with numerous complications, including implant displacement.
      Therefore, the authors have hypothesized that fixation of the Medpor implant with
      fibrin glue (Tisseel, Baxter Healthcare, Norfolk, UK), compared to other fixation
      methods, may be more stable and could provide better results than other fixation
      methods.In this study, 485 patients who had been treated for blowout fractures
      from 2008 to 2012 were evaluated. Medpor implants fixed using Tisseel were used
      to reconstruct bone defects of the orbital wall. The patients' hospital records
      and radiologic images were reviewed according to sex, fracture site, and
      postoperative complications.According to retrospective chart review and
      radiologic evaluation, the complication rate was low and included diplopia (7%;
      33 patients), enophthalmos (4%; 17 patients), and extraocular movement limitation
      (3%; 13 patients).This study suggests that Medpor implant fixation using Tisseel
      is a simpler, more secure, and more suitable for reconstruction of the fractured
      orbital wall compared with other methods. 

PMID- 24036780
TI  - Clinical application of anatomy landmarks for microscopic endonasal
      transsphenoidal surgery for pituitary adenomas.
AB  - It is important to identify relevant anatomical landmarks on the route of
      endonasal transsphenoidal surgery (TSS) for pituitary adenomas to improve the
      gross total resection and the remission of disease. We therefore retrospectively
      studied the clinical outcomes of 148 patients who underwent single nostril
      endonasal TSS for pituitary adenomas. The anatomic basis of these procedures was
      evaluated. The important landmarks included the mucosal sphenoid ostia, the
      sphenoid keel, the osseous ostia and the nutrient arteries nearby, the sellar
      bulge, and the carotid protuberance, which outlined a clear route to the sella
      turcica with the best view and less tissue damage. Based on these landmarks, 148
      cases of endonasal TSS were successfully performed to achieve 70.3% of gross
      total resection and remission, respectively. The complications were controlled to
      the least. Therefore, the application of these landmarks will help to prevent
      complications and improve the long-term outcomes. 

PMID- 24036781
TI  - Transcutaneous lower blepharoplasty, painless suture removal.
AB  - Despite being referred to as one of the more challenging procedures in plastic
      surgery, lower blepharoplasty is one of the most commonly requested and performed
      aesthetic procedures.Our experience, from February 2007 to March 2012, is based
      on 214 transcutaneous lower blepharoplasty procedures in which the skin flap was
      sutured by means of the epidermal-dermal U stitch, a new, simple, and reliable
      method. Patients were followed up for a mean period ranging from 7 to 70 months.
      To our knowledge, the literature proposes a single-stitch closure or continuous
      suture in transcutaneous lower blepharoplasty using nylon or silk 4-5-0 to close
      the skin incision (1-3-5). According to our experience before 2007 based on
      patients' reports, single-stitch subciliary suture removal is a source of stress
      for the patient that causes anxiety, discomfort, and pain.Thus, in February 2007,
      following transepithelial lower blepharoplasty, we started using a new, simple
      way to suture the subciliary skin flap adopting the epidermal-dermal U nylon 5-0
      stitch to avoid any discomfort and drastically reduce the level of anxiety and
      pain at the time of suture removal. According to our experience, the healing of
      the wound does not require any subsequent scar revision resulting from healing
      defects or pathological scar tissue; the complication rate in our series is in
      keeping with that reported by other authors in the literature.In conclusion, our
      experience indicates that the suture technique we describe is an easily
      reproducible, rapid, discomfort-free, and painless means of removing stitches. 

PMID- 24036782
TI  - Disk repositioning surgery of the temporomandibular joint with bioabsorbable
      anchor.
AB  - The most common temporomandibular joint (TMJ) pathologic disease is anterior
      medial displacement of the articular disk, which can lead to TMJ-related
      symptoms.The indication for disk repositioning surgery is irreversible TMJ damage
      associated with temporomandibular pain. We describe a surgical technique using a
      preauricular approach with a high condylectomy to reshape the condylar head. The
      disk is anchored with a bioabsorbable microanchor (Mitek Microfix QuickAnchor
      Plus 1.3) to the lateral aspect of the condylar head. The anchor is linked with a
      3.0 Ethibond absorbable suture to fix the posterolateral side of the disk above
      the condyle.The aims of this surgery were to alleviate temporomandibular pain,
      headaches, and neck pain and to restore good jaw mobility. In the long term, we
      achieved these objectives through restoration of the physiological position and
      function of the disk and the lower articular compartment.In our opinion, the
      bioabsorbable anchor is the best choice for this type of surgery because it
      ensures the stability of the restored disk position and leaves no artifacts in
      the long term that might impede follow-up with magnetic resonance imaging. 

PMID- 24036783
TI  - Simultaneous cheek and lower eyelid reconstruction with combinations of local
      flaps.
AB  - Cheek defects are common facial defects, especially after tumor ablation.
      Although primary repair yields the best aesthetic outcome, wide defects require
      flap resurfacing. Among the flap techniques, the cervicofacial
      rotation/advancement flap is one of the most common. In cases with eyelid
      involvement, it is very unlikely that a local flap would single-handedly
      resurface the defect and additional flaps must be used.This article presents our
      clinical experience with 14 patients with cheek defects for whom cervicofacial
      rotation/advancement flaps were used. In 3 of the 14 patients, local flaps that
      include the laterally based Tripier flap, the Fricke flap, the nasojugal flap,
      and the median forehead flap were combined with the cervicofacial flap to
      reconstruct the lower eyelid defects in accordance with the principle of
      individually reconstructing different anatomic subunits. All infraorbital defects
      were resurfaced with residual cheek and cervical skin with a good color and
      texture match. In patients whose eyelids were intact, no malposition was
      observed.Posteriorly based cervicofacial rotation/advancement flaps offer a very
      reliable and convenient method for resurfacing infraorbital and medial cheek
      defects. When a lower eyelid defect is also present, its individual
      reconstruction as a separate facial subunit needs to be considered using a
      combination of smaller local flaps. 

PMID- 24036784
TI  - Design and application of hybrid maxillomandibular fixation for facial bone
      fractures.
AB  - PURPOSE: A novel maxillomandibular fixation (MMF) procedure using a skeletal
      anchorage screw (SAS) (in the maxilla) and an arch bar (in the mandible), which
      we call "hybrid maxillomandibular fixation," was explored in this study. The aims
      of the study were to examine the efficacy of our hybrid MMF method and to compare
      periodontal tissue health and occlusal rehabilitation among 3 MMF methods.
      MATERIALS AND METHODS: In total, 112 patients who had undergone open reduction at
      the Department of Oral and Maxillofacial Surgery between September 2005 and
      December 2012 were selected for this study. The participants were assigned to one
      of the following groups: SAS (maxilla), SAS (mandible), SAS-arch bar, or arch bar
      arch bar. Periodontal health was evaluated using the Gingival Index, and the
      perioperative occlusal reproducibility was evaluated using a score of 1 to 3.
      Statistical analysis was performed using parametric tests (Student t test or 1
      way analysis of variance followed by post hoc Tukey test). RESULTS: In the
      Gingival Index comparison performed 1 month after the surgery, only the group
      using the arch bars and wiring was significantly different from the other groups
      (P < 0.05). The occlusal reproducibility scores were not significantly different.
      The pain and discomfort of the patients were reduced in the hybrid MMF group.
      CONCLUSIONS: The hybrid MMF takes advantage of MMF using both arch bars and SASs
      for mandibular fractures. In addition, it overcomes many problems presented by
      previous MMF methods.

PMID- 24036785
TI  - Burn scar lipofilling: immunohistochemical and clinical outcomes.
AB  - Over the past years, lipofilling has been used for many pathologies and sequelae;
      recently, its use has also widened for burn outcomes. A total of 93 burn scars
      were assessed (from September 2011 to February 2012). Half of scar area was
      treated through injection of adipose tissue harvested from subcutaneous fat and
      processed in accordance with the Coleman technique. Biopsy specimens were taken
      before treatment and at 3 and 6 months after the treatment. Histologic and
      immunohistochemical evaluations were conducted. In the samples examined, a marked
      improvement was observed, which can be seen in 3 months, but most of all,
      documented at 6 months. In addition, from a clinical point of view, an
      improvement has been documented, both functional and aesthetic. Lipofilling for
      burn scar complete and improve the results of standard surgical procedures, with
      long-term care setting and long-acting results. 

PMID- 24036786
TI  - New practical landmarks to determine sigmoid sinus free zones for suboccipital
      approaches: an anatomical study.
AB  - Literature defines the landmarks to identify the courses and locations of the
      transverse and sigmoid sinuses on the outer surface of the skull and inner
      surface of the scalp. These natural landmarks may only be helpful after skin
      incision and are inadequate to determine the length and size of the skin
      incision. Still, there is a need to identify palpable landmarks easily to
      determine the ideal location to open the initial burr hole before an operation.
      Twenty-eight dried adult human skulls and 2 cadavers were evaluated. The
      zygomatic root, the inion, and the mastoid process were identified on the
      external, and the grooves for sigmoid and transverse sinuses, on the internal
      surfaces. The distances between the 3 landmarks and the midpoints, and the
      shortest distances of the midpoints to the border of the groove for sigmoid sinus
      and groove for transverse sinus were measured. Statistically significant
      differences were evaluated for both sides. Based on the measurements, the defined
      "artificial landmarks" can be considered safe points that involve no vascular
      structures and may be used to perform the initial burr hole during posterolateral
      approaches. Identification of the midpoints and palpation of the defined
      landmarks easily before the operation render the study feasible and practical
      unlike with natural landmarks. To avoid venous injury, the midpoints of mastoid
      inion line and zygomatic root-inion line can be used safely in skin incision
      during posterior fossa approaches and craniotomy. 

PMID- 24036787
TI  - Particle size, temperature, and released amount of fat for safe periorbital fat
      grafts.
AB  - The aim of this study was to determine the particle size, temperature, and amount
      of released fat for safe periorbital fat grafts. From 28 patients, fat was
      suctioned from the abdomen (large particles [LPs]) and from the inner thigh
      (small particles [SPs]) using a 2.1-mm harvesting cannula with a diameter 3.2 *
      1.4-mm hole and a 1-mm hole, respectively. The 10-mL syringes full of fat were
      then put into a centrifuge for 3 minutes (LP) and 1 minute (SP) at 3000
      revolutions/min. Fat was then transferred to a 1-mL syringe with Luer-Lock
      adapters and a blunt cannula of 0.9-mm diameter. The force needed to push the fat
      out of the cannula was measured with a force gauge. The force was measured within
      the different groups according to particle size of the fat, temperature of the
      fat, and released amount of fat. The force needed to push the SP fat out of the
      cannula into the air with minimal amount (MA) (0.01-0.02 mL) injected at room
      temperature (25  degrees C) (1.75 +/- 0.82 N) was significantly greater (P =
      0.000 [t test]) than at body temperature (BT, 33  degrees C) (1.27 +/- 0.38 N).
      At BT, the force needed to push the SP fat into subcutaneous pig tissue (2.30 +/-
      1.46 N) was significantly lesser (P = 0.000 [t test]) than LP fat (6.54 +/- 2.39
      N). At BT, the force needed to push the MA of SP fat into pig subcutaneous tissue
      (1.38 +/- 0.26 N) was significantly lesser (P = 0.000 [t test]) than the force
      needed to push the usual amount (0.03-0.04 mL) of SP fat (3.83 +/- 1.78 N). The
      force needed to push the fat into human lower eyelids at room temperature (4.06
      +/- 2.26 N) was significantly greater (P = 0.000 [t test]) than at BT (2.11 +/-
      0.96 N). At BT, the force needed to inject an MA of SP fat into human lower
      eyelids (1.55 +/- 0.83 N) was significantly lesser (P = 0.000 [t test]) than the
      force needed to inject a usual amount of fat (2.78 +/- 1.03 N). We suggest
      injections of the SP (1-mm hole diameter harvesting cannula) fat with MAs (0.01
      0.02 mL) by means of fragmented incremental injections stored at BT (33 degrees
      C) to reduce the injection pressure.

PMID- 24036788
TI  - Microvascular sutureless adhesive bonding anastomosis with a new soluble hollow
      stent.
AB  - The aim of this study was to assess a new soluble hollow stent used in an
      experimental sutureless adhesive bonding technique for microvascular anastomosis.
      Twenty-four New Zealand white rabbits were randomized into 2 groups. Twelve end
      to-end anastomoses of carotid arteries were performed with glue and stent in
      group A. In control group B, 12 anastomoses were performed by manual suturing.
      Anastomoses were timed; immediate and late patency at 1 day, 7 days, and 3 weeks
      after surgery were evaluated by ultrasonography. Specimens were then analyzed
      histologically. This adhesive bonding technique took 7.02 +/- 1.26 minutes to
      perform while the hand-sewn technique took 15.48 +/- 2.10 minutes. Immediate and
      late patencies of the 2 groups were not statistically different. The new
      technique using glue and stent appeared to be timesaving, feasible, and
      efficient. 

PMID- 24036789
TI  - Blow-in fracture of the orbit.
AB  - We report 2 patients with blow-in fractures of the orbital floor caused by
      different mechanisms. In a 17-year-old boy, a sudden impact was given to the
      anterior maxillary wall and caused a depression fracture of a maxilla, yet the
      infraorbital rim remained intact. We think fragments of the orbital floor were
      forced into the orbit by a sudden increase in pressure in the maxillary sinus in
      this patient. In a 51-year-old man, the impact of a force was on the
      laterosuperior part of the zygoma, which pushed the zygoma medially. These 2
      cases represent 2 different mechanisms of blow-in fractures of the orbital floor.

PMID- 24036790
TI  - Variable expressivity and clinical heterogeneity can complicate the diagnosis and
      management of Pfeiffer syndrome.
AB  - We report here a newborn female infant with striking features consistent with
      severe Pfeiffer syndrome (PS). Pfeiffer syndrome is a rare craniofacial disorder
      that has an autosomal dominant mode of inheritance (OMIM 101600). Our patient had
      unexpected differences between her clinical features and those predicted from her
      genetic tests. The following clinical features were noted: severe exophthalmos,
      syndactyly, upper extremity contractures, and relative macroglossia. A head
      computed tomography with three-dimensional reconstruction showed that she did not
      have craniosynostosis. Genetic tests included a normal 46,XX karyotype and a
      chromosomal microarray that revealed a copy number gain at 14q23.1 as well as a
      copy number loss at 16p13.2. FGFR2 sequencing revealed a c.870G>T transversion in
      exon 8, which is predicted to encode a Trp290Cys substitution.The clinical
      features of severe exophthalmos and other features typical of PS without
      craniosynostosis were most consistent with a diagnosis of PS type III. However,
      her Trp290Cys FGFR2 mutation is reported to be associated with PS type II that
      includes kleeblatschadel (or "cloverleaf") skull anomalies as a cardinal feature.
      Our patient's lack of craniosynostosis predicted from this mutation is a striking
      example of variable expressivity. Such discrepancies between the physical
      findings (phenotype) and the mutation identified (genotype) and the association
      of different findings with different mutations in the same gene (clinical
      heterogeneity) can present difficulties in case management. Clinicians should be
      guided by careful phenotyping rather than by genotypic predictions alone. 

PMID- 24036791
TI  - Type II first branchial cleft anomaly.
AB  - First branchial cleft anomaly is a rare disease of the head and neck. It accounts
      for less than 8% of all branchial abnormalities. It is classified into type I,
      which is thought to arise from the duplication of the membranous external ear
      canal and are composed of ectoderm only, and type II that have ectoderm and
      mesoderm. Because of its rarity, first branchial cleft anomaly is often
      misdiagnosed and results in inappropriate management. A 9-year-old girl presented
      to us with fistula in the submandibular region and discharge in the external ear.
      Under general anesthesia, complete surgical excision of the fistula tract was
      done through step-ladder approach, and the histopathologic examination confirmed
      the diagnosis of type II first branchial cleft anomaly. 

PMID- 24036792
TI  - The role of computer-assisted design and modeling in an edentulous mandibular
      malunion reconstruction.
AB  - Mandibular trauma is a common problem encountered by the craniofacial surgeon.
      Fractures in the edentulous mandible represent only 3% of these injuries, and
      optimal management is controversial. This problem is further compounded by
      malunion and malocclusion when fracture lines heal in incorrect positions. Even
      with recent advances in imaging and hardware systems, they remain difficult
      problems that often require multiple operations to obtain satisfactory results.
      We present a 69-year-old man with an edentulous mandibular fracture and
      concomitant malocclusion after a series of unsuccessful operations. By using
      computer-assisted design and manufacturing technology, we were able to plan
      osteotomies for correct anatomic positioning, which restored dental occlusion and
      facial aesthetics. A follow-up at 6 months postoperatively revealed a stable and
      anatomic reconstruction. 

PMID- 24036797
TI  - A "ping-pong" fracture of the frontal sinus.

PMID- 24036798
TI  - Penetrant injury of the nose with a foreign material.

PMID- 24036799
TI  - Submandibular cystic cavernous hemangioma: an unusual presentation.

PMID- 24036800
TI  - Airway obstruction after orthognathic surgery.

PMID- 24036801
TI  - Sublingual hematoma after usual warfarin dose.

PMID- 24036802
TI  - Excision of ranula using injection of hydrocolloid dental impression material.

PMID- 24036803
TI  - A giant neuroglial heterotopia.

PMID- 24036804
TI  - Mucoepidermoid carcinoma of the larynx.

PMID- 24036805
TI  - Bilateral internal acoustic canal mass.
AB  - We reported a case of bilateral internal acoustic canal mass. A 42-year-old man
      patient was previously treated for colon cancer. After surgery during
      chemotherapy signs as severe vertigo and bilateral sudden hearing loss occurred.
      Temporal bone magnetic resonance imaging (MRI) had bilateral internal acoustic
      canal masses. 

PMID- 24036806
TI  - An unusual epiglottis synechiae managed with transoral robotic surgery in a
      patient with pemphigus vulgaris.

PMID- 24036807
TI  - Removal of reconstruction plates after treatment of mandibular fractures.

PMID- 24036808
TI  - Is there a need to modify the mouth gag for palatoplasty?

PMID- 24036809
TI  - Recurrence of ameloblastoma in soft tissue.

PMID- 24036810
TI  - The extent of chin ptosis and lower incisor exposure changes following the
      osseous genioplasties.
AB  - The incision and dissection of the mentalis muscles are inevitable to access the
      osteotomy line during genial surgery. As the mentalis muscles elevate the central
      lower lip and support the lip vertically, inadvertent scarring or lengthening of
      these muscles may lead to lip incompetence and may increase the lower incisor
      exposure (LIE) that will cause an unaesthetic result. The aim of this study was
      to evaluate the extent of lip ptosis, LIE, and other soft-tissue changes
      following different types of osseous genioplasty procedures.Twenty-nine patients
      (18 females, 11 males) were included in this study. Patients were classified into
      3 groups with respect to their genial movement type as genial setback (n = 10),
      genial advancement (n = 10), and vertical reduction (n = 9). Preoperative and
      postoperative lateral cephalograms were analyzed to evaluate the horizontal and
      vertical soft-tissue changes of the lower lip and chin in the 3 genioplasty
      groups. The statistical evaluations were performed with regression analysis. The
      mean increase in the LIE was 1.88 mm. Lower incisor exposure and soft-tissue
      thickness at pogonion were increased significantly in all patients (P < 0.05).
      Statistically significant differences for lower lip length and vertical position
      of soft-tissue supramentale values were detected in patients who underwent
      vertical reduction genioplasty (P < 0.05). Genioplasty procedures requiring the
      mentalis muscle release cause a 1.88-mm increase in LIE. Vertical positional
      alterations of the lower lip were especially observed following the vertical
      reduction genioplasty. Clinician should be aware of this consequence in the
      course of treatment planning. 

PMID- 24036811
TI  - Comparison studies of different flaps for reconstruction of buccal defects.
AB  - Our purpose was to evaluate the feasibility of radial forearm free (RFF) flap,
      platysma myocutaneous (PM) flap, and anterolateral thigh (ALT) flap in buccal
      reconstruction. This study consisted of 56 patients who were categorized into 3
      groups. The Student t test was used to analyze the variables. Patients in group
      platysma flap were significantly older, the dissection of platysma flap was
      easier, and the defect was significantly smaller than those in group radial
      forearm flap and group ALT flap. The reduction in the widths of mouth opening
      between group PM, group RFF, and group ALT were compared. However, the reduction
      of mouth-opening widths in group RFF and group ALT was significantly less than
      that in group PM. Platysma myocutaneous flap may be more suitable in patients
      with small to middle-size defect and poor status, although the flap cannot
      achieve a reliable result; anterolateral thigh flap and radial forearm flap can
      preserve the interincisal distance well even for large buccal defect, but it
      takes more time and skills in the operation. 

PMID- 24036812
TI  - A novel flap for the reconstruction of midcheek defects: "rabbit ear flap".
AB  - Cheek defects generally occur because of reasons such as trauma, burn, and tumor
      excisions. In the reconstruction of cheek defects, it is essential to cover the
      defects using the tissues with compatible color and similar texture. Although
      many techniques have been described for this purpose, local flaps are more likely
      to be used.In this study, we describe a new technique named "rabbit ear flap,"
      which we used for the reconstruction of a 4.5 * 7-cm cheek defect due to basal
      cell carcinoma excision in a 71-year-old male patient. Two separate flaps on the
      extension of right facial artery with an inferior pedicle on the nasolabial
      region (hairless skin) and a superior pedicle flap that extended from right oral
      commissure to the submandibular region (hairy skin) were used. The hairy skin
      part of the defect was closed via the hairy skin flap, whereas the hairless
      region was closed with the hairless skin flap. The donor sites were closed
      primarily.No complication was encountered in the early or long-term follow-ups.
      In the 28-month follow-up of the patient, it was observed that the color and
      texture compatibility was fine, the natural beard integrity was obtained, the
      donor site scarring was minimal, and the scarring was camouflaged well in the
      anatomical lines.This technique is supposed to be an alternative method for
      reconstruction of medium-sized cheek defects because it is a simple, reliable,
      and single-session procedure, and because of its similar color and texture, it
      offers satisfactory aesthetic and functional outcomes due to natural beard
      restoration. 

PMID- 24036813
TI  - Characteristics and management of patients requiring hospitalization for
      treatment of odontogenic infections.
AB  - Odontogenic infections usually respond well to outpatient care; however, these
      can be very complicated and demand hospitalization. The aim of this study was to
      assess retrospectively the characteristics and medical management of patients
      needing hospitalization for the treatment of odontogenic infections. The personal
      data, symptoms presented, and therapeutic procedures adopted were analyzed. The
      predominant age group was from 0 to 10 years (30%), and a sex relation of 1:1 was
      found, but there was no significant difference (P = 0.337). The most frequent
      diagnosis was of dentoalveolar abscess (86.3%). Pain (47.1%) was the prevailing
      reason for hospitalization, with pulpal necrosis (67.5%) as the main cause. There
      was a prevalence of involvement of the lower permanent teeth (41.4%) and lower
      deciduous teeth (23%). The prevalent clinical aspect was submandibular or facial
      swelling (61.4%). The most administered antibiotic was penicillin G associated
      with metronidazole (25.3%). Most cases (58.7%) presented regression with
      antibiotic therapy, and in some cases, surgical drainage was necessary (18.7%).
      One case of Ludwig angina resulted in death. The mean length of hospital stay was
      4.4 days, being higher in the cases of Ludwig angina. It was concluded that most
      cases of odontogenic infections requiring hospitalization were of dentoalveolar
      abscess occurring in young people of both sexes, associated to the lower
      permanent molar teeth, presenting with swelling, with regression of the symptoms
      after antibiotic therapy and hospitalization for some days, with some of the
      cases requiring drainage. 

PMID- 24036814
TI  - Different lymphoproliferative disorders in different salivary glands of primary
      Sjogren syndrome.
AB  - We report 1 case of primary Sjogren syndrome that showed histologic variation and
      different lymphoproliferative disorders in different salivary glands.Different
      salivary glands can show a different transition situation with histologic
      variation and lymphoproliferative disorders. The larger salivary glands have more
      potentially progressive transition situation than smaller glands. These findings
      also supported the theory that the transition of reactive B cells from
      lymphoepithelial sialadenitis to monoclonal lymphoma is generally a multistep
      process in different salivary glands within 1 person. 

PMID- 24036815
TI  - The application of the anterior cervical flap in major head and neck surgery.
AB  - We present a case of a 79-year-old male patient, who was diagnosed with a primary
      squamous cell carcinoma of the left parotid region that was fungating through the
      skin and infiltrating the sternocleidomastoid muscle. Clinically and
      radiologically, the patient was staged as T3 N2b M0. He underwent a near-total
      parotidectomy with facial nerve preservation in conjunction with a modified
      radical neck dissection and wide excision of the involved skin to remove all the
      disease in a monobloc fashion. A regional cutaneous flap, the anterior cervical
      flap was used for reconstruction of a large surgical defect. 

PMID- 24036816
TI  - The characteristics and second intention healing after shave excision of nevi on
      the lid margin in East Asians.
AB  - AIM: The aim of this study was to report the characteristics and secondary
      intention healing after shave excision of nevi on the lid margin in East Asians.
      METHODS: Forty patients who underwent shave biopsy of an eyelid mass and were
      diagnosed with a nevus were retrospectively evaluated regarding their sex and age
      and the location, size, complication, and recurrence of the nevus. In all
      patients, shave biopsy was performed carefully to induce secondary-intention
      wound healing, and they received follow-up for at least 1 year. RESULTS: Among 40
      patients, 21 were men, and 19 were women. The average age of the patients was
      35.3 +/- 14.9 years. Twenty-one nevi were found on the upper lid, and 19 were
      found on the lower lid. In 1 patient, nevi were found on both the upper and lower
      lids. There were no significant differences in incidence according to sex and
      location of the nevi (upper or lower lid); however, the half that were located in
      the nasal area and the dermal type of nevus were the most common. Junctional nevi
      were not found in any of our cases. There were no complications and recurrences
      found in our cases, even after shave excision. CONCLUSIONS: Eyelid nevi in Korean
      patients commonly develop at a young age. There was no difference in the
      incidence of nevi between the upper and lower lids, but the nasal area of the lid
      was a more common location for the development of a nevus. The dermal type was
      the most common in our cases. Healing by secondary intention is a safe and
      effective alternative to surgical reconstruction after a shave excision of nevi
      on lid margin.

PMID- 24036817
TI  - Moving the mandible to the retruded contact position for simulating the hinge
      movement in virtual three-dimensional orthognathic surgery by integrating the
      plaster models.
AB  - The range of rotation of the mandible during virtual three-dimensional
      orthognathic surgery is small and may be similar to the hinge movement of the
      mandible. This current study offers a new method to move the mandible to the
      retruded contact position (RCP), a position of beginning hinge movement, during
      virtual three-dimensional orthognathic surgery. During this method, a three
      dimensional skull model was reconstructed from the computed tomographic images in
      the Mimics software. Then the RCP in the patient could be obtained using Gothic
      arch tracer or swallowing method and was recorded using a wax plate, followed by
      transferring to plaster models. Subsequently, the plaster models in RCP were
      scanned using a dental surface scanner and imported into the Mimics software.
      Finally, we could move the mandible to the RCP based on the registration between
      the three-dimensional skull model and plaster model for simulating the hinge
      movement during virtual three-dimensional orthognathic surgery. This may be a
      small step forward for improving the accuracy of virtual three-dimensional
      orthognathic surgery. 

PMID- 24036818
TI  - Modern therapy for severe alveolar ridge atrophy.
AB  - This clinical report illustrates a modern method for oral rehabilitation of
      severe edentulous atrophic ridge. Shallow vestibule and small denture-bearing
      area of the maxilla provide insufficient retention, and only the symphyseal
      region of the mandible has obvious alveolar ridge. The surgery of deepening
      vestibule of the maxilla ridge was done by using tentative miniscrew combined
      with old denture and soft liner. The osseointegrated dental implants were
      installed over symphyseal region of the mandible to act as retentive devices for
      prostheses. In addition, functional reline with rebase material to build buccal
      tongue contact over the retromolar area after denture delivery obtained high
      satisfaction from the patient. Many clinical conditions cannot be managed solely
      with implants or preprosthetic surgery alone, whereas a combination of the 2 can
      achieve successful outcome. 

PMID- 24036819
TI  - Management of pure medial orbital wall fracture with autogenous bone graft.
AB  - The orbit is an irregular conical cavity formed from 7 bones including the
      frontal, sphenoid, zygomatic, maxillary, ethmoid, lacrimal, and palatine bones.
      Fractures of the internal orbit can cause a number of problems, including
      diplopia, ocular muscle entrapment, and enophthalmos. Although muscle entrapment
      is relatively rare, diplopia and enophthalmos are relatively common sequelae of
      internal orbital fractures. Medial orbital wall fracture is relatively uncommon
      and represents a challenge for its anatomical reconstruction. In this context,
      autogenous bone graft has been the criterion standard to provide framework for
      facial skeleton and orbital walls. Therefore, it is possible to harvest grafts of
      varying size and contour, and the operation is performed through the bicoronal
      incision, which is the usual approach to major orbital reconstruction. Thus, this
      article aimed to describe a patient with a pure medial orbital wall fracture, and
      it was causing diplopia and enophthalmos. The orbital fracture was treated using
      autogenous bone graft from calvarial bone. The authors show a follow-up of 12
      months, with facial symmetry and without diplopia and enophthalmos. In addition,
      a computed tomography scan shows excellent bone healing at the anterior and
      posterior parts of the medial orbital wall reconstruction. 

PMID- 24036820
TI  - Hypoplastic epiglottis in a nonsyndromic child: a rare cause of chronic cough.
AB  - We describe a 2-year-old girl born out of a nonconsanguineous marriage who
      presented with dry cough since birth, which was often associated with feeding.
      She never had any choking or cyanotic/apneic spells. Her voice and cry were
      normal. She was born at term with no obvious congenital anomalies or perinatal
      problems. The child never had any other significant illness or respiratory
      distress to warrant hospital admission. On examination, she was a healthy-looking
      child without any abnormal syndromic facies or craniofacial or any other
      congenital anomaly. Flexible bronchoscopy done under sedation and local
      anesthesia revealed a rounded, short, stump-like hypoplastic epiglottis with a
      smooth contour. The rest of the laryngeal apparatus and the trachea-bronchial
      tree had normal appearance. The parents were advised to feed the child in a
      propped-up position and thickening of feeds to avoid aspirations. She remains
      well under follow-up. Hypoplastic epiglottis is a rare congenital anomaly of the
      upper airway, which can present with chronic cough. Endoscopic evaluation of the
      upper airway should be considered early in children presenting with cough
      associated with feeding problems. 

PMID- 24036821
TI  - Using the "bottom-up and outside-in" sequence for panfacial fracture management:
      does it provide a clinical significance?
AB  - Panfacial fractures usually refer to simultaneous facial fractures, which affect
      the upper, middle, and lower thirds of the face. The management of panfacial
      fracture is complex because of the lack of reliable landmarks. Literature has
      shown many approaches for management of panfacial fractures. Every segment of
      bone has a precise function in the repair. Therefore, the "bottom-up and outside
      in" sequence is the most widely used approach in the management of panfacial
      fractures. These facial fractures present remarkable challenges for both
      experienced and inexperienced surgeons. This article aimed to report a case of a
      panfacial fracture (mandibular condylar and symphysis fractures associated with
      an atypical Le Fort III fracture) in a 48-year-old man. The patient was
      successfully treated using bottom-up and outside-in sequence by accessing all
      facial injuries. Postoperatively, radiograph examination revealed good reduction
      and fixation of titanium plates, and physical examination revealed good
      functional and esthetic outcomes. 

PMID- 24036822
TI  - Rhabdomyomatous mesenchymal hamartoma of nasal vestibule.
AB  - Rhabdomyomatous mesenchymal hamartoma is a rare congenital tumor and usually
      occurring in the head and neck. Characteristically, this tumor is composed of
      various mesenchymal elements such as adipose tissue, blood vessels, collagen
      fibers, elastic fibers, and peripheral nerves in random orientation. We present a
      7-year-old boy with an intranasal mass developed after the trauma and who had a
      diagnosis of rhabdomyomatous mesenchymal hamartoma. 

PMID- 24036823
TI  - A bizarre cause of extensive oronasal fistula.
AB  - Oronasal fistula is defined as an abnormal duct, connecting the nasal with the
      oral cavity. We present an extremely rare case of oronasal fistula associated
      with rhinolithiasis. The particular case presents the unique feature of a palatal
      defect, being large enough to enable the in toto removal of the rhinolith. A 2
      layer closure of the fistula was finally undertaken, by utilizing a vestibular
      and a palatal mucoperiosteal flap. 

PMID- 24036824
TI  - Strategy to minimize oral mucosal tear and lip injury in facial contouring and
      orthognathic surgery.
AB  - In this article, the authors present a simple but effective technical strategy to
      protect the lip and mucosa from iatrogenic thermal injury and traumatic mucosal
      tear in orthognathic and aesthetic facial contouring surgery. During surgical
      exposure and osteotomy, a piece of double-layered Vaseline dressing gauze is
      strategically placed over the lip and mucosal tissues before the application of
      the Obwegeser or Gimma retractors. The objective is to avoid traumatic and
      thermal injury to the lip and mucosal tissues during the use of various
      retractors and other craniomaxillofacial dynamic instruments in such surgery. In
      our experience of consecutive 400 intraoral osteotomy procedures over the last 5
      years of using the double-layered Vaseline gauze to protect the lip tissues and
      oral mucosa, there was no incidence of any unintentional complications of thermal
      injury and tears of the lip and mucosa. It is simple and effective with minimum
      learning curve, but most importantly it has significantly minimized the morbidity
      associated with lip thermal injury and mucosal tear in these patients. 

PMID- 24036825
TI  - Versatility of retroauricular mastoid donor site: a convenient valuable warehouse
      of various free graft tissues in cosmetic and reconstructive surgery.
AB  - Soft-tissue deficiency is a critical issue in facial cosmetic and reconstructive
      surgery. Harvesting autografts from other anatomical sites has been a common
      practice in overcoming soft-tissue insufficiency for many years. However, donor
      site complications and visible scars are of important concerns. Therefore, we
      would like to introduce an alternative donor site of free-tissue grafts and its
      inherent advantages: the retroauricular mastoid area located along the mastoid
      hair line. From August 1991 to June 2011, we performed facial reconstructive
      surgeries for cosmetic correction of disfigurements from both congenital and
      complications of previous cosmetic procedures on a total of 213 patients. These
      patients had undergone either 1 or more facial cosmetic surgeries in the past. In
      this study, our primary goal focused on revising facial asymmetries or defects
      from previous surgical scars, tissue contraction, undercorrection, or
      underdevelopment. For autograft harvesting, we incised an elliptical shape along
      the retroauricular hairline. We then harvested sufficient amount of skin, dermal
      fat, fascia, or a piece of the mastoid bone if needed. After harvesting, we
      closed the incisional area and covered it with a compressive dressing. In
      evaluation of our results, we compared the preoperative photographs with
      postoperative and constructed a survey on patient satisfaction. Overall, the
      patients in this study were greatly satisfied with their surgical results. No
      major complications were reported. As a result of our long-term study, we believe
      that the retroauricular mastoid area has been shown to be an indispensable donor
      site for a variety of autograft tissues in terms of safety, convenience, and
      versatility of its unique structural composition consisting of skin, dermal fat,
      fascia, and bone. 

PMID- 24036826
TI  - Late surgical treatment of posttraumatic mandibular deformity.
AB  - Delays in treatment may complicate the treatment of mandibular trauma, leading to
      a bone healing in an abnormal position and to a posttraumatic mandibular
      deformity such as malunion, malocclusion, and asymmetry. All these features may
      make delayed treatment a challenging issue. Therefore, early reduction and
      fixation of displaced mandibular fractures is mandatory to allow precocious
      healing and return to the normal function. In this article, we describe a patient
      treated in our unit for a diagnosed posttraumatic malocclusion after lack of
      primary trauma treatment. 

PMID- 24036827
TI  - Quality of life in oral cancer patients-effects of tongue resection and
      sociocultural aspects.
AB  - BACKGROUND: The aims of this study were to evaluate postoperative quality of life
      in patients who have had resections of tongue cancer and reconstruction by flaps
      and to collect information about their sociocultural situation. METHODS: In this
      cross-sectional study, patients with primary tongue cancer treated with total and
      subtotal tongue resection in the First Affiliated Hospital of Zhengzhou
      University, between July 2008 and October 2011, were included. Quality of life
      was assessed by the 14-item Oral Health Impact Profile and the Medical Outcomes
      Study-Short Form 36 questionnaires 12 months postoperatively. Furthermore, a
      questionnaire about the sociocultural background of the patients was applied.
      RESULTS: Forty-six of the 62 questionnaires were returned (74.19%). In the
      Medical Outcomes Study-Short Form 36, the best-scoring domain was bodily pain,
      whereas the lowest scores were for social functioning and vitality. In the 14
      item Oral Health Impact Profile, the lowest-scoring domain was psychological
      disability, followed by psychological discomfort and social disability.
      CONCLUSIONS: The postoperative quality of life in our patients was significantly
      influenced by tongue resection. This should be considered for surgical planning.
      The sociocultural data showed a rather low education level and life standard
      level for the majority of the patients.

PMID- 24036828
TI  - Herpes zoster laryngitis accompanied by Ramsay Hunt syndrome.
AB  - The most common presentation of herpes zoster in the head and neck region is
      called Ramsay Hunt syndrome (RHS), which rarely accompanies multiple cranial
      neuropathy. Herpes zoster also involves the mucous membrane of the tongue,
      palate, pharynx, and larynx. Herpes zoster infection of the larynx accompanied by
      Ramsay Hunt syndrome with cranial polyneuropathy is extremely rare, with only few
      reported cases in the literature. At the time of this report, a review of the
      medical literature disclosed 4 reported cases of herpes zoster laryngitis
      accompanied by Ramsay Hunt syndrome. Herein, we present 2 additional cases and
      report the clinical outcome of cranial polyneuropathy with a review of the
      literature. 

PMID- 24036829
TI  - An explosion in the oral cavity by a firecracker.
AB  - Explosive oral cavity injuries make restoring optimal oral function a challenge.
      An explosion in the oral cavity can cause burns and concomitant smoke inhalation
      injury to the upper airway.We present the case of a patient in whom the middle
      and lower thirds of the face were destroyed when a firecracker exploded in his
      oral cavity. Gunpowder tattooing caused by the explosion was present on the
      retropharyngeal space. He had an open fracture of the mandibular symphysis and
      inhalation burns of the upper airway were suspected. Tracheostomy was performed
      because we could not rule out inhalation burns of the upper airway. After close
      observation, his cardiopulmonary function and vital signs were stable, and we
      prepared him for reconstructive surgery. 

PMID- 24036830
TI  - Angiofibroma of inferior turbinate as an unusual complication of CO2 laser
      turbinoplasty.
AB  - Angiofibroma is a benign vascular tumor that usually occurs in the nasopharynx,
      and extranasopharyngeal angiofibromas are rarely reported. We report the first
      case of an angiofibroma arising from the inferior turbinate after CO2 laser
      turbinoplasty. Endoscopic excisional biopsy was performed, but the tumor recurred
      after 2 months of surgery. The mass was excised by endoscopic approach including
      surrounding normal mucosal tissue. Histologic examination suggested the diagnosis
      of angiofibroma. The patient was asymptomatic, and there was no evidence of
      recurrence after 1 year of the second surgery. 

PMID- 24036831
TI  - Spontaneous hemorrhage of a facial neurofibroma: endovascular embolization before
      surgical intervention.
AB  - A 50-year-old man with neurofibromatosis type 1 presented to the emergency
      department after a spontaneous hemorrhage into a facial plexiform neurofibroma.
      An emergent selective angiography of the external carotid artery was performed
      with Onyx embolization of the origin of the internal maxillary artery as well as
      the superficial temporal artery to minimize arterial bleeding during the
      subsequent operative hematoma evacuation. This technique was aimed to control
      blood loss during the surgical procedure and reduce the amount of transfusion
      product required for resuscitation. This technique provides a viable option to
      control potentially life-threatening arterial bleeding in emergent settings. 

PMID- 24036832
TI  - Rehabilitation of maxillary cleft with hybrid obturator prosthesis.
AB  - The hybrid obturator prosthesis aims to provide a sense of well-being to the
      patient, offering improvements in speech, chewing, and swallowing. Thus, the
      retention and stabilization of the prosthesis become decisive factors for the
      success of the rehabilitation treatment. The objective of this study was to
      describe the treatment of a 70-year-old man with a congenital maxillary cleft
      performed through aesthetic and functional prosthetic rehabilitation with hybrid
      obturator prosthesis. In this study, the fabricated prosthesis achieved its
      purpose by providing adequate functional and aesthetic conditions to the patient,
      promoting the reduction of airspace through the sealing of the oronasal
      communication, with consequent improvement in the quality of life. 

PMID- 24036833
TI  - Postoperative maxillary cyst after maxillary sinus augmentation.
AB  - The posterior edentulous maxilla is a critical anatomic region for dental implant
      therapy. Because of severe alveolar bone resorption and maxillary sinus
      pneumatization, low bone volume is often presented clinically. Although maxillary
      sinus augmentation has been developed to promote bone reconstruction and oral
      rehabilitation, complications have been reported. Possible complications include
      paranasal sinusitis, loss of the graft, and displacement of an implant into the
      antrum. In this study, we present an observed rare complication of maxillary
      sinus augmentation, a postoperative maxillary cyst that occurred 10 years after
      treatment. 

PMID- 24036834
TI  - Five-year follow-up of modified implant-supported overdenture in an iliac crest
      autograft failure: clinical report.
AB  - The treatment of extensive pathologic lesions in the jaw, most of the time, can
      generate rehabilitation problems to the patient. The solid ameloblastoma is a
      locally invasive odontogenic tumor with a high recurrence rate. Its treatment is
      aggressive and accomplished through resection with safety margin. The criterion
      standard for reconstruction is autogenous bone, but it can provide a high degree
      of resorption, causing inconvenience to the patient because of lack of
      rehabilitative option. This study aimed to describe a patient with ameloblastoma
      treated through resection and reconstruction with autogenous bone graft, in
      which, after an extensive resorption of the graft was made, a modified bar was
      applied to support a prosthetic implant overdenture. 

PMID- 24036835
TI  - Odontogenic infection causing orbital cellulitis in a pediatric patient.
AB  - Odontogenic abscess can become an orbital cellulitis, causing potentially serious
      intracranial and orbital complications. The full clinical complications from
      odontogenic orbital cellulitis in a pediatric patient are rarely seen daily in
      hospital emergency departments. Thus, odontogenic orbital cellulitis still
      remains a rarity, resulting in a medical challenge. With this in mind, this study
      aimed to describe a case of periorbital and orbital cellulitis resulting from
      odontogenic origin in a 6-year-old patient who was successfully treated by
      performing intravenous antibiotic administration combined with surgical drainage.

PMID- 24036836
TI  - Submandibular triangle masses.
AB  - OBJECTIVE: The study aims to analyze the demographic data of a large case series
      operated on because of submandibular triangle mass for more than 10 years and
      presents a review of the literature. MATERIALS AND METHODS: The charts of
      patients who underwent surgical intervention for submandibular triangle mass
      between January 2000 and November 2010 were reviewed. The medical history, age,
      sex, duration of symptoms, clinical presentation, preoperative investigations,
      and histopathologic diagnosis were reviewed. RESULTS: The study included 66
      subjects; 12 patients (18.2%) with submandibular sialolithiasis, 18 patients
      (27.2%) with sialadenitis, 10 patients with lymphadenitis (15.1%), and 26
      patients (39.3%) with tumors. Of the tumors, 23% was malignant and 77% was
      benign. Benign tumors of submandibular gland comprised 22.7% and malign tumors of
      submandibular gland comprised 3% of all submandibular mass. The most common
      benign tumor was pleomorphic adenoma. The most frequent histopathologic diagnoses
      of submandibular masses originated from the submandibular gland, and these
      comprised 71.2% of all submandibular mass pathologies. The main symptom was a
      painless mass. Ultrasonography was the most common preoperative diagnostic
      procedure. Fine-needle aspiration biopsy was performed in 26 patients. A clear
      diagnosis could not be provided in 3 (12%) patients. CONCLUSION: Infectious
      conditions and benign tumors are more frequent than malign tumors in the
      submandibular region. The histopathologic diagnoses mainly consisted of
      submandibular sialadenitis, sialolithiasis, pleomorphic adenoma, and
      lymphadenitis. Ultrasonography is the first option of radiologic evaluation. Fine
      needle aspiration biopsy is a very useful and usually sufficient diagnostic
      procedure for histopathologic diagnosis. Excisional biopsy can be performed when
      the fine-needle aspiration biopsy failed.

PMID- 24036837
TI  - Bilateral submandibular gland aplasia with hypertrophy of the sublingual glands
      of a patient with a cleft lip and palate: case report.
AB  - Aplasia of major salivary glands is a rare disorder with only a handful of cases
      reported in the literature. The cause of congenital absence of the salivary
      glands has not been determined, but it may be associated with ectodermal defects
      of the first and second branchial arches. Patients may be asymptomatic or may
      experience dysphagia, xerostomia, several periodontal disease, or multiple
      caries. There are few reports of patients with congenital gland aplasia with
      cleft lip and palate. We document the case of a 41-year-old patient with repaired
      unilateral cleft lip palate, bilateral submandibular gland aplasia, and
      compensatory hypertrophy of the sublingual glands. To the best of our knowledge,
      there are no previous reports that can be found in the literature with a
      combination of such findings. 

PMID- 24036838
TI  - Postoperative complications of central neurocytoma.
AB  - Six patients with central neurocytoma were retrospectively examined, including
      diagnosis and treatment process as well as postoperative complications. Clinical
      follow-ups were performed through telephone calls or outpatient service. Of the 6
      patients, a total of 5 patients had 1 or more postoperative complications. The
      postoperative complications included hydrocephalus, basal ganglia edema, epidural
      hematoma of the operated region and the remote region, and intracranial
      infection; 5 patients underwent the cortical fistulization approach and 1
      underwent the longitudinal fissure-corpus callosum approach. The neoplasms of 3
      patients were totally resected and those of the other 3 patients were subtotally
      resected. Preoperative accurate diagnosis of central neurocytoma is of great
      importance for the drawing up of the operation strategy; in addition to magnetic
      resonance imaging and computed tomography, digital subtraction angiography and
      magnetic resonance spectroscopy could be helpful for the preoperative diagnosis
      of central neurocytoma. Subtotal resection of the lesion and the longitudinal
      fissure-corpus callosum approach may be useful for the reduction of postoperative
      complications. 

PMID- 24036839
TI  - The retinoic acid receptor agonist Am80 increases mucosal inflammation in an IL-6
      dependent manner during Trichuris muris infection.
AB  - PURPOSE: Vitamin A metabolites, such as all-trans-retinoic acid (RA) that act
      through the nuclear receptor; retinoic acid receptor (RAR), have been shown to
      polarise T cells towards Th2, and to be important in resistance to helminth
      infections. Co-incidentally, people harbouring intestinal parasites are often
      supplemented with vitamin A, as both vitamin A deficiency and parasite infections
      often occur in the same regions of the globe. However, the impact of vitamin A
      supplementation on gut inflammation caused by intestinal parasites is not yet
      completely understood. METHODS: Here, we use Trichuris muris, a helminth parasite
      that buries into the large intestine of mice causing mucosal inflammation, as a
      model of both human trichuriasis and IBD, treat with an RARalpha/beta agonist
      (Am80) and quantify the ensuing pathological changes in the gut. RESULTS:
      Critically, we show, for the first time, that rather than playing an anti
      inflammatory role, Am80 actually exacerbates helminth-driven inflammation,
      demonstrated by an increased colonic crypt length and a significant CD4(+) T cell
      infiltrate. Further, we established that the Am80-driven crypt hyperplasia and
      CD4(+) T cell infiltrate were dependent on IL-6, as both were absent in Am80
      treated IL-6 knock-out mice. CONCLUSIONS: This study presents novel data showing
      a pro-inflammatory role of RAR ligands in T. muris infection, and implies an
      undesirable effect for the administration of vitamin A during chronic helminth
      infection.

PMID- 24036840
TI  - Nanodiamond landmarks for subcellular multimodal optical and electron imaging.
AB  - There is a growing need for biolabels that can be used in both optical and
      electron microscopies, are non-cytotoxic, and do not photobleach. Such biolabels
      could enable targeted nanoscale imaging of sub-cellular structures, and help to
      establish correlations between conjugation-delivered biomolecules and function.
      Here we demonstrate a sub-cellular multi-modal imaging methodology that enables
      localization of inert particulate probes, consisting of nanodiamonds having
      fluorescent nitrogen-vacancy centers. These are functionalized to target specific
      structures, and are observable by both optical and electron microscopies.
      Nanodiamonds targeted to the nuclear pore complex are rapidly localized in
      electron-microscopy diffraction mode to enable "zooming-in" to regions of
      interest for detailed structural investigations. Optical microscopies reveal
      nanodiamonds for in-vitro tracking or uptake-confirmation. The approach is
      general, works down to the single nanodiamond level, and can leverage the unique
      capabilities of nanodiamonds, such as biocompatibility, sensitive magnetometry,
      and gene and drug delivery. 

PMID- 24036841
TI  - Maternal ileal interposition surgery confers metabolic improvements to offspring
      independent of effects on maternal body weight in UCD-T2DM rats.
AB  - BACKGROUND: Increasing numbers of people are undergoing bariatric surgery, of
      which approximately half are women in their childbearing years. However,
      information on the long-term effects of maternal bariatric surgery in their
      children is lacking. Furthermore, since bariatric surgery is performed to reduce
      body weight, clinical studies have not been able to differentiate between
      benefits to the child due to maternal body weight loss versus other maternal
      postoperative metabolic changes. Therefore, we used the University of California,
      Davis, type 2 diabetes mellitus (UCD-T2DM) rat model to test the hypothesis that
      maternal ileal interposition (IT) surgery would confer beneficial metabolic
      effects in offspring, independent of effects on maternal body weight. METHODS: IT
      surgery was performed on 2-month-old prediabetic female UCD-T2DM rats. Females
      were bred 3 weeks after surgery, and male pups were studied longitudinally.
      RESULTS: Maternal IT surgery resulted in decreased body weight in offspring
      compared with sham offspring (P < 0.05). IT offspring exhibited improvements of
      glucose-stimulated insulin secretion and nutrient-stimulated glucagon-like
      peptide-2 (GLP-2) secretion (P < 0.05). Fasting plasma unconjugated bile acid
      concentrations were 4-fold lower in IT offspring compared with sham offspring at
      two months of age (P < 0.001). CONCLUSIONS: Overall, maternal IT surgery confers
      modest improvements of body weight and improves insulin secretion and nutrient
      stimulated GLP-2 secretion in offspring in the UCD-T2DM rat model of type 2
      diabetes, indicating that this is a useful model for investigating the weight
      independent metabolic effects of maternal bariatric surgery.

PMID- 24036842
TI  - Systemic lidocaine to improve quality of recovery after laparoscopic bariatric
      surgery: a randomized double-blinded placebo-controlled trial.
AB  - BACKGROUND: Few multimodal strategies to minimize postoperative pain and improve
      recovery have been examined in morbidly obese patients undergoing laparoscopic
      bariatric surgery. The main objective of this study was to evaluate the effect of
      systemic intraoperative lidocaine on postoperative quality of recovery when
      compared to saline. METHODS: The study was a prospective randomized, double
      blinded placebo-controlled clinical trial. Subjects undergoing laparoscopic
      bariatric surgery were randomized to receive lidocaine (1.5 mg/kg bolus followed
      by a 2 mg/kg/h infusion until the end of the surgical procedure) or the same
      volume of saline. The primary outcome was the quality of recovery 40
      questionnaire at 24 h after surgery. RESULTS: Fifty-one subjects were recruited
      and 50 completed the study. The global QoR-40 scores at 24 h were greater in the
      lidocaine group median (IQR) of 165 (151 to 170) compared to the saline group,
      median (IQR) of 146 (130 to 169), P = 0.01. Total 24 h opioid consumption was
      lower in the lidocaine group, median (IQR) of 26 (19 to 46) mg IV morphine
      equivalents compared to the saline group, median (IQR) of 36 (24 to 65) mg IV
      morphine equivalents, P = 0.03. Linear regression demonstrated an inverse
      relationship between the total 24 h opioid consumption (IV morphine equivalents)
      and 24 h postoperative quality of recovery (P < 0.0001). CONCLUSIONS: Systemic
      lidocaine improves postoperative quality of recovery in patients undergoing
      laparoscopic bariatric surgery. Patients who received lidocaine had a lower
      opioid consumption which translated to a better quality of recovery.

PMID- 24036843
TI  - Arp2/3 complex inhibitors adversely affect actin cytoskeleton remodeling in the
      cultured murine kidney collecting duct M-1 cells.
AB  - Dynamic remodeling of the actin cytoskeleton plays an essential role in cell
      migration and various signaling processes in living cells. One of the critical
      factors that controls the nucleation of new actin filaments in eukaryotic cells
      is the actin-related protein 2/3 (Arp2/3) complex. Recently, two novel classes of
      small molecules that bind to different sites on the Arp2/3 complex and inhibit
      its ability to nucleate F-actin have been discovered and described. The current
      study aims at investigating the effects of CK-0944666 (CK-666) and its analogs
      (CK-869 and inactive CK-689) on the reorganization of the actin microfilaments in
      the cortical collecting duct cell line, M-1. We show that treatment with CK-666
      and CK869 results in the reorganization of F-actin and drastically affects cell
      motility rate. The concentrations of the compounds used in this study (100-200
      MUM) neither cause loss of cell viability nor influence cell shape or monolayer
      integrity; hence, the effects of described compounds were not due to structural
      side effects. Therefore, we conclude that the Arp2/3 complex plays an important
      role in cell motility and F-actin reorganization in M-1 cells. Furthermore, CK
      666 and its analogs are useful tools for the investigation of the Arp2/3 complex.

PMID- 24036844
TI  - Histones and lung cancer: Are the histone deacetylases a promising therapeutic
      target?
AB  - PURPOSE: Deoxyribonucleic acid is wrapped around an octamer of core histone
      proteins to form a nucleosome, the basic structure of chromatin. Two main
      families of enzymes maintain the equilibrium of acetyl groups added to or removed
      from lysine residues. Histone deacetylases (HDACs) catalyze the removal of acetyl
      groups from lysine residues in histone amino termini and non-histone proteins
      also, leading to chromatin condensation and transcriptional repression. HDAC
      overexpression, resulting in tumor suppressor genes silencing, has been found in
      several human cancer tissues, indicating that aberrant epigenetic activity is
      associated with cancer development. Therefore, inhibitors of these enzymes are
      emerging anticancer agents and there is evidence supporting their role in
      hematological malignancies. The minimal efficacy of conventional chemotherapy has
      prompted a renewed focus on targeted therapy based on pathways altered during the
      pathogenesis of lung cancer. We identify the pleiotropic antitumor effects of
      HDAC inhibitors in lung cancer, focusing on the result caused by their use
      individually, as well as in combination with other chemotherapeutic agents, in
      lung cancer cell lines and in clinical trials. METHOD: We searched reviews and
      original papers in Pubmed over the last 10 years. RESULTS: We identified 76
      original papers on this topic. CONCLUSIONS: Numerous preclinical studies have
      shown that HDAC inhibitors exhibit impressive antitumor activity in lung cancer
      cell lines. Nevertheless, Phase III randomized studies do not support HDAC
      inhibitors use in lung cancer patients in everyday practice. Ongoing and future
      studies would help determine their role in lung cancer treatment.

PMID- 24036845
TI  - Tumour tissue selectivity in the uptake and retention of SN 28049, a new
      topoisomerase II-directed anticancer agent.
AB  - PURPOSE: A variety of anticancer drugs, including doxorubicin and mitoxantrone,
      have structures in which a DNA-intercalating chromophore is linked to a
      positively charged side chain. These drugs generally inhibit tumour growth and
      survival by poisoning the enzyme DNA topoisomerase II. SN 28049, a
      benzonaphthyridine derivative with these properties, has curative activity
      against the Colon 38 tumour in mice. Previous pharmacokinetic studies have
      demonstrated tumour-selective retention with approximately 20-fold higher area
      under the concentration-time curve (AUC) for tumour tissue as compared to normal
      tissues. We have investigated here whether such retention is tumour specific.
      METHODS: Plasma and tissue pharmacokinetics were assessed in the murine Lewis
      lung (LL3) tumour in C57 BL/6 mice and in xenografts of the NZM4, NZM10 and NZM52
      human melanoma lines in Balb/c Rag-1 immunodeficient mice. The in vitro cellular
      localisation of SN 28049 in murine and human cell lines was studied by confocal
      fluorescence microscopy. RESULTS: A 260-fold variation, from 8.9 MUM h (NZM4) to
      2,334 MUM h (Colon 38), was found among the different tumours. Only small
      variations were observed in the corresponding plasma AUC (2.9-5 MUM h). Moreover,
      in vivo activity, as measured by tumour growth delay, varied from 1 day (NZM4) to
      curative (Colon 38), consistent with the tumour pharmacokinetic data. In cultured
      cell lines, SN 28049 was found in cytoplasmic bodies, suggesting that drug
      sequestration could contribute to tumour pharmacokinetics. CONCLUSION: SN 28049
      shows dramatic differences in both tumour AUC and antitumour activity against
      different tumours. These differences point to the presence of a tumour-specific
      uptake and retention mechanism.

PMID- 24036846
TI  - Calcium carbonate does not affect nilotinib pharmacokinetics in healthy
      volunteers.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Gastric upset is a common side effect
      of nilotinib therapy, and calcium carbonate is frequently used concomitantly,
      either as antacid or as calcium supplementation. With the increasing number of
      oral agents in cancer therapy, oral drug-drug interactions are becoming more
      relevant. Nilotinib has already been shown to be absorbed to a much lesser extent
      when co-administered with proton pump inhibitors. Because exposure to sub
      therapeutic concentrations of anticancer drugs such as nilotinib may result in
      selection of resistant clones and ultimately relapse, we studied the effect of a
      calcium carbonate supplement (Tums Ultra 1000(r)) on nilotinib pharmacokinetics.
      WHAT THIS STUDY ADDS: Calcium carbonate may be co-administered with nilotinib
      without significantly affecting the pharmacokinetics of nilotinib and potentially
      impacting efficacy. PURPOSE: Nilotinib is a second-generation oral tyrosine
      kinase inhibitor with superior efficacy compared with imatinib mesylate in the
      treatment for chronic phase chronic myelogenous leukemia. Calcium carbonate is
      commonly used as a source of calcium supplementation or as antacid to ameliorate
      the gastrointestinal side effects associated with nilotinib, which could have
      unknown effects on nilotinib absorption. The purpose of this study was to provide
      information on the effect of calcium carbonate on the PK of nilotinib in healthy
      volunteers. METHODS: Healthy subjects were enrolled in a two-period, open-label,
      single-institution, randomized, cross-over, fixed-schedule study. In one period,
      each subject received 400 mg of nilotinib p.o. In the other period, 4,000 mg of
      calcium carbonate (4 X Tums Ultra 1000(r)) was administered p.o. 15 min prior to
      the nilotinib dose. Plasma samples were collected at specified timepoints,
      concentrations of nilotinib were quantitated by LC-MS, and data were analyzed non
      compartmentally. RESULTS: Eleven subjects were evaluable. Calcium supplementation
      did not significantly affect nilotinib pharmacokinetic parameters including area
      under the plasma concentration versus time curve (18.4 MUg/mL h alone vs. 16.9
      MUg/mL h with calcium carbonate, p = 0.83; 80 % power); maximum plasma
      concentration (C(max)) (0.670 MUg/mL alone vs. 6.18 MUg/mL with calcium
      carbonate, p = 0.97); or half-life (18.9 h alone vs. 17.2 h with calcium
      carbonate, p = 0.18). CONCLUSIONS: Our results indicate that the use of calcium
      carbonate does not significantly affect nilotinib pharmacokinetics.

PMID- 24036847
TI  - Knockdown of cyclophilin A reverses paclitaxel resistance in human endometrial
      cancer cells via suppression of MAPK kinase pathways.
AB  - PURPOSE: Paclitaxel resistance remains to be a major obstacle to the chemotherapy
      of endometrial cancer. Using proteomic-based approach, we used to identify
      cyclophilin A (CypA) as a potential therapeutic target for endometrial cancer. As
      a natural continuation, this study aimed to reveal the correlation between CypA
      and paclitaxel resistance and evaluate the possibility of CypA as a therapeutic
      target for reversal of resistance. METHODS: Two paclitaxel-resistant endometrial
      cancer cell sublines HEC-1-B/TAX and AN3CA/TAX were generated, and expressions of
      CypA, P-gp, MRP-2 and survivin were demonstrated by Western blotting. CypA was
      knocked down by RNA interference, and the subsequent effects on the alteration of
      paclitaxel resistance were examined by MTT, flow cytometry and migratory/invasive
      transwell assays. MAPK kinases activities were examined by Western blotting.
      RESULTS: CypA knockdown led to significant inhibition of cell proliferation,
      induction of apoptosis and suppression of migratory/invasive capacity in HEC-1
      B/TAX and AN3CA/TAX cells when exposed to paclitaxel. CypA knockdown led to
      reductions in total and phosphorylated MAPK kinases, including Akt, ERK1/2, p38
      MAPK and JNK, in HEC-1-B/TAX cells. Furthermore, pretreatment with MAPK kinase
      inhibitors exhibited a synergistic effect in combination with CypA knockdown.
      CONCLUSIONS: These results demonstrated that CypA expression was up-regulated in
      paclitaxel-resistant cancer cells, and knockdown of CypA could reverse the
      paclitaxel resistance through, at least partly, suppression of MAPK kinase
      pathways, presenting a possibility of CypA serving as a therapeutic target to
      overcome paclitaxel resistance.

PMID- 24036848
TI  - Single-cell dynamics of the chromosome replication and cell division cycles in
      mycobacteria.
AB  - During the bacterial cell cycle, chromosome replication and cell division must be
      coordinated with overall cell growth in order to maintain the correct ploidy and
      cell size. The spatial and temporal coordination of these processes in
      mycobacteria is not understood. Here we use microfluidics and time-lapse
      fluorescence microscopy to measure the dynamics of cell growth, division and
      chromosome replication in single cells of Mycobacterium smegmatis. We find that
      single-cell growth is size-dependent (large cells grow faster than small cells),
      which implicates a size-control mechanism in cell-size homoeostasis. Asymmetric
      division of mother cells gives rise to unequally sized sibling cells that grow at
      different velocities but show no differential sensitivity to antibiotics.
      Individual cells are restricted to one round of chromosome replication per cell
      division cycle, although replication usually initiates in the mother cell before
      cytokinesis and terminates in the daughter cells after cytokinesis. These studies
      reveal important differences between cell cycle organization in mycobacteria
      compared with better-studied model organisms. 

PMID- 24036849
TI  - Endurance training in MS: short-term immune responses and their relation to
      cardiorespiratory fitness, health-related quality of life, and fatigue.
AB  - The influences of exercise on cytokine response, health-related quality of life
      (HR-QoL), and fatigue are important aspects of MS rehabilitation. Physical
      exercises performed within these programs are often practiced in water, but the
      effects of immersion have not been investigated. To investigate the influences of
      short-term immune responses and cardiorespiratory fitness on HR-QoL and fatigue
      during 3 weeks endurance training conducted on a cycle-ergometer or an aquatic
      bike. Randomized controlled clinical trial in 60 MS patients. HR-QoL, fatigue,
      cardiorespiratory fitness, and short-term immune changes (serum concentrations in
      response to cardiopulmonary exercise test) of brain-derived neurotrophic factor
      (BDNF), nerve growth factor (NGF), interleukin-6, and the soluble receptor of IL
      6 (sIL-6R) were determined at the beginning and end of 3 weeks of training
      intervention. Subjects performed daily 30 min training at 60 % of their VO2peak.
      SF-36 total (p = 0.031), physical (p = 0.004), and mental health (p = 0.057)
      scores show time effects within both groups. Between-group effects were shown for
      FSMC total (p = 0.040) and motor function score (p = 0.041). MFIS physical
      fatigue showed time effects (p = 0.008) for both groups. Linear regression models
      showed relationships between short-term immune responses and cardiorespiratory
      fitness with HR-QoL and fatigue after the intervention. This study indicates
      beneficial effects of endurance training independent of the training setting.
      Short-term immune adaptations and cardiorespiratory fitness have the potential to
      influence HR-QoL and fatigue in persons with MS. The specific immune responses of
      immersion to exercise need further clarification.

PMID- 24036850
TI  - An adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
      accompanied by brain calcifications: a case report and a literature review of
      brain calcifications disorders.

PMID- 24036851
TI  - Targeting protein kinase CK2 suppresses prosurvival signaling pathways and growth
      of glioblastoma.
AB  - PURPOSE: Gliomas are the most frequently occurring primary malignancies in the
      brain, and glioblastoma is the most aggressive of these tumors. Protein kinase
      CK2 is composed of two catalytic subunits (alpha and/or alpha') and two beta
      regulatory subunits. CK2 suppresses apoptosis, promotes neoangiogenesis, and
      enhances activation of the JAK/STAT, NF-kappaB, PI3K/AKT, Hsp90, Wnt, and
      Hedgehog pathways. Aberrant activation of the NF-kappaB, PI3K/AKT, and JAK/STAT-3
      pathways is implicated in glioblastoma progression. As CK2 is involved in their
      activation, the expression and function of CK2 in glioblastoma was evaluated.
      EXPERIMENTAL DESIGN AND RESULTS: Analysis of 537 glioblastomas from The Cancer
      Genome Atlas Project demonstrates the CSNK2A1 gene, encoding CK2alpha, has gene
      dosage gains in glioblastoma (33.7%), and is significantly associated with the
      classical glioblastoma subtype. Inhibition of CK2 activity by CX-4945, a
      selective CK2 inhibitor, or CK2 knockdown by siRNA suppresses activation of the
      JAK/STAT, NF-kappaB, and AKT pathways and downstream gene expression in human
      glioblastoma xenografts. On a functional level, CX-4945 treatment decreases the
      adhesion and migration of glioblastoma cells, in part through inhibition of
      integrin beta1 and alpha4 expression. In vivo, CX-4945 inhibits activation of
      STAT-3, NF-kappaB p65, and AKT, and promotes survival of mice with intracranial
      human glioblastoma xenografts. CONCLUSIONS: CK2 inhibitors may be considered for
      treatment of patients with glioblastoma.

PMID- 24036852
TI  - Clinical monoclonal B lymphocytosis versus Rai 0 chronic lymphocytic leukemia: A
      comparison of cellular, cytogenetic, molecular, and clinical features.
AB  - PURPOSE: To investigate the incidence and clinical relevance of classic and new
      prognostic markers, IGHV gene mutational status, and chromosomal abnormalities in
      clinical monoclonal B lymphocytosis (cMBL) compared with Rai stage 0 chronic
      lymphocytic leukemia (Rai0-CLL). EXPERIMENTAL DESIGN: A group of 136 patients
      with cMBL and a group of 216 Rai0-CLL cases were investigated prospectively.
      RESULTS: IGHV-mutated cases were significantly more frequent among cMBLs (P =
      0.005), whereas the distribution of CD38 and ZAP-70 positive cases, of patients
      with NOTCH1 and SF3B1 mutations or exhibiting the major CLL cytogenetic
      abnormalities, was similar in the two groups. Moreover, no significant
      differences were found either in IGHV/IGHD/IGHJ gene usage or in the overall
      prevalence of stereotyped IGHV gene sequences. Cells from cMBL and Rai0-CLL
      exhibited similar gene and microRNA (miRNA) signatures; in addition, when grouped
      according to the IGHV mutational status, IGHV-unmutated cases showed different
      transcriptional signatures compared with IGHV-mutated patients, irrespective of
      the cMBL or Rai0-CLL classification. cMBL diagnosis per se was predictive of
      longer progression-free survival. CONCLUSIONS: Our study based on a prospective
      series of patients indicates that no major differences exist between the
      circulating cells from cMBL and Rai0-CLL, at least based on a comparison of the
      markers used in the study. This possibly suggests that the two conditions mainly
      differ in the initial size of the monoclonal cell population, which may influence
      the subsequent timing of clonal expansion and clinical manifestations.

PMID- 24036853
TI  - Variation within 3'-UTRs of base excision repair genes and response to therapy in
      colorectal cancer patients: A potential modulation of microRNAs binding.
AB  - PURPOSE: Colorectal cancer is routinely treated with a 5-fluorouracil (5-FU)
      based chemotherapy. 5-FU incorporates into DNA, and the base excision repair
      (BER) pathway specifically recognizes such damage. We investigated the
      association of single-nucleotide polymorphisms (SNP) in the 3'-untranslated
      regions (UTR) of BER genes, and potentially affecting the microRNA (miRNA)
      binding, on the risk of colorectal cancer, its progression, and prognosis. SNPs
      in miRNA-binding sites may modulate the posttranscriptional regulation of gene
      expression operated by miRNAs and explain interindividual variability in BER
      capacity and response to 5-FU. EXPERIMENTAL DESIGN: We tested 12 SNPs in the 3'
      UTRs of five BER genes for colorectal cancer susceptibility in a case-control
      study (1,098 cases and 1,459 healthy controls). Subsequently, we analyzed the
      role of these SNPs on clinical outcomes of patients (866 in the Training set and
      232 in the Replication set). RESULTS: SNPs in the SMUG1 and NEIL2 genes were
      associated with overall survival. In particular, SMUG1 rs2233921 TT carriers
      showed increased survival compared with those with GT/GG genotypes [HR, 0.54; 95%
      confidence interval (CI), 0.36-0.81; P = 0.003] in the Training set and after
      pooling results from the Replication set. The association was more significant
      following stratification for 5-FU-based chemotherapy (P = 5.6 * 10(-5)). A
      reduced expression of the reporter gene for the T allele of rs2233921 was
      observed when compared with the common G allele by in vitro assay. None of the
      genotyped BER polymorphisms were associated with colorectal cancer risk.
      CONCLUSIONS: We provide the first evidence that variations in miRNA-binding sites
      in BER genes 3'-UTR may modulate colorectal cancer prognosis and therapy
      response.

PMID- 24036855
TI  - Influence of water-insoluble nonionic copolymer E(6)P(39)E(6) on the
      microstructure and self-aggregation dynamics of aqueous SDS solution-NMR and SANS
      investigations.
AB  - The influence of water-insoluble nonionic triblock copolymer PEO-PPO-PEO
      [poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)] i.e., E6P39E6
      with molecular weight 2800, on the microstructure and self-aggregation dynamics
      of anionic surfactant sodium dodecylsulfate (SDS) in aqueous solution (D2O) were
      investigated using high resolution nuclear magnetic resonance (NMR) and small
      angle neutron scattering (SANS) measurements. Variable concentration and
      temperature proton ((1)H), carbon ((13)C) NMR chemical shifts, (1)H self
      diffusion coefficients, (1)H spin-lattice and spin-spin relaxation rates data
      indicate that the higher hydrophobic nature of copolymer significantly influenced
      aggregation characteristics of SDS. The salient features of the NMR
      investigations include (i) the onset of mixed micelles at lower SDS
      concentrations (<3 mM) relative to the copolymer-free case and their evolution
      into SDS free micelles at higher SDS concentrations (~30 mM), (ii) disintegration
      of copolymer-SDS mixed aggregate at moderate SDS concentrations (~10 mM) and
      still binding of a copolymer with SDS and (iii) preferential localization of the
      copolymer occurred at the SDS micelle surface. SANS investigations indicate
      prolate ellipsoidal shaped mixed aggregates with an increase in SDS aggregation
      number, while a contrasting behavior in the copolymer aggregation is observed.
      The aggregation features of SDS and the copolymer, the sizes of mixed aggregates
      and the degree of counterion dissociation (alpha) extracted from SANS data
      analysis corroborate reasonably well with those of (1)H NMR self-diffusion and
      sodium ((23)Na) spin-lattice relaxation data.

PMID- 24036854
TI  - Targeted nanomedicine for suppression of CD44 and simultaneous cell death
      induction in ovarian cancer: an optimal delivery of siRNA and anticancer drug.
AB  - PURPOSE: The proposed project is aimed at enhancing the efficiency of epithelial
      ovarian cancer treatment and reducing adverse side effects of chemotherapy using
      nanotechnology. Overexpression of the CD44 membrane receptor results in tumor
      initiation, growth, cancer stem cells' specific behavior, development of drug
      resistance, and metastases. We hypothesize that a developed cancer-targeted
      delivery system that combines CD44 siRNA with paclitaxel would successfully
      deliver its payload inside cancer cells, effectively induce cell death, and
      prevent metastases. EXPERIMENTAL DESIGN: We synthesized, characterized, and
      tested a nanoscale-based drug delivery system (DDS) containing a modified
      polypropylenimine (PPI) dendrimer as a carrier; anticancer drug paclitaxel as a
      cell death inducer; a synthetic analog of luteinizing hormone-releasing hormone
      (LHRH) peptide as a tumor-targeting moiety; and siRNA targeted to CD44 mRNA. The
      proposed DDS was tested in vitro and in vivo using metastatic ovarian cancer
      cells isolated from patients with malignant ascites. RESULTS: We found that in
      contrast with cells isolated from primary tumors, CD44 was highly overexpressed
      in metastatic cancer cells. Treatment with the proposed tumor-targeted nanoscale
      based nucleic acid and DDS led to the suppression of CD44 mRNA and protein,
      efficient induction of cell death, effective tumor shrinkage, and prevention of
      adverse side effects on healthy organs. CONCLUSION: We show a high therapeutic
      potential for combinatorial treatment of ovarian carcinoma with a novel DDS that
      effectively transports siRNA targeting to CD44 mRNA simultaneously with cytotoxic
      agents. Clin Cancer Res; 19(22); 6193-204. (c)2013 AACR.

PMID- 24036856
TI  - Evaluation of the sensitivity of two 3D diode array dosimetry systems to setup
      error for quality assurance (QA) of volumetric-modulated arc therapy (VMAT).
AB  - The purpose of this study is to evaluate the sensitivities of 3D diode arrays to
      setup error for patient-specific quality assurance (QA) of volumetric-modulated
      arc therapy (VMAT). Translational setup errors of +/- 1, +/- 2, and +/- 3 mm in
      the RL, SI, and AP directions and rotational setup errors of +/- 1 degrees  and
      +/- 2 degrees  in the pitch, roll, and yaw directions were set up in two phantom
      systems, ArcCHECK and Delta4, with VMAT plans for 11 patients. Cone-beam computed
      tomography (CBCT) followed by automatic correction using a HexaPOD 6D treatment
      couch ensured the position accuracy. Dose distributions of the two phantoms were
      compared in order to evaluate the agreement between calculated and measured
      values by using gamma analysis with 3%/3 mm, 3%/2 mm, and 2%/2 mm criteria. To
      determine the impact on setup error for VMAT QA, we evaluated the sensitivity of
      results acquired by both 3D diode array systems to setup errors in translation
      and rotation. For the VMAT QA of all patients, the pass rate with the 3%/3 mm
      criteria exceeded 95% using either phantom. For setup errors of 3 mm and 2
      degrees , respectively, the pass rates with the 3%/3mm criteria decreased by a
      maximum of 14.0% and 23.5% using ArcCHECK, and 14.4% and 5.0% using Delta4. Both
      systems are sensitive to setup error, and do not have mechanisms to account for
      setup errors in the software. The sensitivity of both VMAT QA systems was
      strongly dependent on the patient-specific plan. The sensitivity of ArcCHECK to
      the rotational error was higher than that of Delta4. In order to achieve less
      than 3% mean pass rate reduction of VMAT plan QA with the 3%/3 mm criteria, a
      setup accuracy of 2 mm/1 degrees  and 2 mm/2 degrees  is required for ArcCheck
      and Delta4 devices, respectively. The cumulative effect of the combined 2 mm
      translational and 1 degrees  rotational errors caused 3.8% and 2.4% mean pass
      rates reduction with 3%/3 mm criteria, respectively, for ArcCHECK and Delta4
      systems. For QA of VMAT plans for nasopharyngeal cancer (NPC) using the ArcCHECK
      system, the setup should be more accurate. 

PMID- 24036857
TI  - Development of real-time motion verification system using in-room optical images
      for respiratory-gated radiotherapy.
AB  - Phase-based respiratory-gated radiotherapy relies on the reproducibility of
      patient breathing during the treatment. To monitor the positional reproducibility
      of patient breathing against a 4D CT simulation, we developed a real-time motion
      verification system (RMVS) using an optical tracking technology. The system in
      the treatment room was integrated with a real-time position management system. To
      test the system, an anthropomorphic phantom that was mounted on a motion platform
      moved on a programmed breathing pattern and then underwent a 4D CT simulation
      with RPM. The phase-resolved anterior surface lines were extracted from the 4D CT
      data to constitute 4D reference lines. In the treatment room, three infrared
      reflective markers were attached on the superior, middle, and inferior parts of
      the phantom along with the body midline and then RMVS could track those markers
      using an optical camera system. The real-time phase information extracted from
      RPM was delivered to RMVS via in-house network software. Thus, the real-time
      anterior-posterior positions of the markers were simultaneously compared with the
      4D reference lines. The technical feasibility of RMVS was evaluated by repeating
      the above procedure under several scenarios such as ideal case (with identical
      motion parameters between simulation and treatment), cycle change, baseline
      shift, displacement change, and breathing type changes (abdominal or chest
      breathing). The system capability for operating under irregular breathing was
      also investigated using real patient data. The evaluation results showed that
      RMVS has a competence to detect phase-matching errors between patient's motion
      during the treatment and 4D CT simulation. Thus, we concluded that RMVS could be
      used as an online quality assurance tool for phase-based gating treatments. 

PMID- 24036858
TI  - Effects of interportal error on dose distribution in patients undergoing breath
      holding intensity-modulated radiotherapy for pancreatic cancer: evaluation of a
      new treatment planning method.
AB  - In patients with pancreatic cancer, intensity-modulated radiotherapy (IMRT) under
      breath holding facilitates concentration of the radiation dose in the tumor,
      while sparing the neighboring organs at risk and minimizing interplay effects
      between movement of the multileaf collimator and motion of the internal
      structures. Although the breath-holding technique provides high interportal
      reproducibility of target position, dosimetric errors caused by interportal
      breath-holding positional error have not been reported. Here, we investigated the
      effects of interportal breath-holding positional errors on IMRT dose distribution
      by incorporating interportal positional error into the original treatment plan,
      using random numbers in ten patients treated for pancreatic cancer. We also
      developed a treatment planning technique that shortens breath-holding time
      without increasing dosimetric quality assurance workload. The key feature of our
      proposed method is performance of dose calculation using the same optimized
      fluence map as the original plan, after dose per fraction in the original plan
      was cut in half and the number of fractions was doubled. Results confirmed that
      interportal error had a negligible effect on dose distribution over multiple
      fractions. Variations in the homogeneity index and the dose delivered to 98%, 2%,
      and 50% of the volume for the planning target volume, and the dose delivered to 1
      cc of the volume for the duodenum and stomach were +/-1%, on average, in
      comparison with the original plan. The new treatment planning method decreased
      breath-holding time by 33%, and differences in dose-volume metrics between the
      original and the new treatment plans were within +/- 1%. An additional advantage
      of our proposed method is that interportal errors can be better averaged out;
      thus, dose distribution in the proposed method may be closer to the planned dose
      distribution than with the original plans. 

PMID- 24036859
TI  - A Monte Carlo study on electron and neutron contamination caused by the presence
      of hip prosthesis in photon mode of a 15 MV Siemens PRIMUS linac.
AB  - Several investigators have pointed out that electron and neutron contamination
      from high-energy photon beams are clinically important. The aim of this study is
      to assess electron and neutron contamination production by various prostheses in
      a high-energy photon beam of a medical linac. A 15 MV Siemens PRIMUS linac was
      simulated by MCNPX Monte Carlo (MC) code and the results of percentage depth dose
      (PDD) and dose profile values were compared with the measured data. Electron and
      neutron contaminations were calculated on the beam's central axis for Co-Cr-Mo,
      stainless steel, Ti-alloy, and Ti hip prostheses through MC simulations. Dose
      increase factor (DIF) was calculated as the ratio of electron (neutron) dose at a
      point for 10 * 10 cm2 field size in presence of prosthesis to that at the same
      point in absence of prosthesis. DIF was estimated at different depths in a water
      phantom. Our MC-calculated PDD and dose profile data are in good agreement with
      the corresponding measured values. Maximum dose increase factor for electron
      contamination for Co-Cr-Mo, stainless steel, Ti-alloy, and Ti prostheses were
      equal to 1.18, 1.16, 1.16, and 1.14, respectively. The corresponding values for
      neutron contamination were respectively equal to: 184.55, 137.33, 40.66, and
      43.17. Titanium-based prostheses are recommended for the orthopedic practice of
      hip junction replacement. When treatment planning for a patient with hip
      prosthesis is performed for a high-energy photon beam, attempt should be made to
      ensure that the prosthesis is not exposed to primary photons. 

PMID- 24036860
TI  - Evaluation of the influence of tumor location and size on the difference of dose
      calculation between Ray Tracing algorithm and Fast Monte Carlo algorithm in
      stereotactic body radiotherapy of non-small cell lung cancer using CyberKnife.
AB  - This study evaluated the extent of improvement in dose predication accuracy
      achieved by the Fast Monte Carlo algorithm (MC) compared to the Ray Tracing
      algorithm (RAT) in stereotactic body radiotherapy (SBRT) of non-small cell lung
      cancer (NSCLC), and how their differences were influenced by the tumor site and
      size. Thirty-three NSCLC patients treated with SBRT by CyberKnife in 2011 were
      recruited. They were divided into the central target group (n = 17) and
      peripheral target group (n = 16) according to the RTOG 0236 guidelines. Each
      group was further divided into the large and small target subgroups. After the
      computation of treatment plans using RAT, a MC plan was generated using the same
      patient data and treatment parameters. Apart from the target reference point dose
      measurements, various dose parameters for the planning target volume (PTV) and
      organs at risk (OARs) were assessed. In addition, the "Fractional Deviation"
      (FDev) was also calculated for comparison, which was defined as the ratio of the
      RAT and MC values. For peripheral lung cases, RAT produced significantly higher
      dose values in all the reference points than MC. The FDev of all reference point
      doses and dose parameters was greater in the small target than the large target
      subgroup. For central lung cases, there was no significant reference point and
      OAR dose differences between RAT and MC. When comparing between the small target
      and large target subgroups, the FDev values of all the dose parameters and
      reference point doses did not show significant difference. Despite the shorter
      computation time, RAT was inferior to MC, in which the target dose was usually
      overestimated. RAT would not be recommended for SBRT of peripheral lung tumors
      regardless of the target size. However, it could be considered for large central
      lung tumors because its performance was comparable to MC. 

PMID- 24036861
TI  - Negative margin technique - a novel planning strategy to improve dose
      conformation in SBRT using dynamic conformal arc delivery.
AB  - The purpose of this study was to introduce a planning strategy for dynamic
      conformal arc therapy (DCAT), named negative margin technique (NMT), and evaluate
      its dosimetric gain in lung stereotactic body radiation therapy (SBRT). In DCAT,
      the field aperture is continuously conformed to the planning target volume (PTV)
      with an aperture margin (AM) to compensate for the penumbra effect with gantry
      rotation. It is a common belief the AM should be positive (or at least 'zero').
      However, the radial penumbra width becomes significantly wider because of
      continuously overlapped beams in arc delivery. Therefore, we hypothesize if the
      'negative margin' is applied in the radial direction, it would improve the PTV
      dose conformation while reducing normal tissue dose. For verification, trial
      plans were made using the NMT and compared with 'zero margin (ZM)' plans for five
      lung SBRT cases representing different situations depending on the location of
      the PTV and organs at risk. All plans met 95% PTV coverage with the prescription
      dose and spared the spinal cord below the tolerance. Two conventional
      conformation indices (the ratio of prescription isodose volume to the PTV (CI100)
      and the ratio of 50% prescription isodose volume to the PTV (CI50)) and a
      modified conformation index were investigated. The maximum dose at 2 cm from the
      PTV (Dmax-2cm) and the percent of lung volume receiving 20 Gy (V20) were also
      evaluated. Another planning simulation was performed with a total of ten randomly
      selected lung SBRT cases to mimic actual practice. In this simulation,
      optimization with ZM was first performed and further optimization using the NMT
      was processed for cases that could not meet a goal of CI100 = 1.2 with the ZM
      optimization. In all cases, both the CI100 and CI50 values were significantly
      reduced (overall, 9.4% +/- 4.1% and 5.9%+/- 3.1% for CI100 and CI50,
      respectively). The modified conformation index values also showed similar
      improvement (overall, 10.1% +/- 5.7% increase). Reduction of Dmax-2cm was also
      observed in all cases (4.5% +/- 2.2%). V20 values decreased in all cases but one
      (5.7% +/- 3.9%, excluding the increased case). In the random group simulation, it
      was possible to achieve the goal with just one NMT trial for five out of six
      cases that did not meet the goal in the ZM optimization. Interestingly, however,
      one case needed as many as six iterations to get the CI100 = 1.2 goal. The NMT
      turned out to be an effective planning strategy that could bring significant
      improvement of dose conformation. The NMT can be easily implemented in most
      clinics with no prerequisite. 

PMID- 24036862
TI  - Monte Carlo characterization of biocompatible beta-emitting 90Y glass seed
      incorporated with the radionuclide 153Sm as a SPECT marker for brachytherapy
      applications.
AB  - A glass seed consisting of the beta--emitting radionuclide 90Y incorporated with
      radionuclide 153Sm as SPECT marker is proposed for potential application in
      brachytherapy in order to reduce the undesirable dose to healthy adjacent organs.
      The aim of this work is to determine the dosimetric characteristics, as suggested
      in the AAPM TG-60/TG-149 reports, for this seed using Monte Carlo simulation.
      Monte Carlo codes MCNP5, EGSnrc, and FLUKA were used to calculate the absorbed
      dose distribution around the seed. Dosimetric parameters, such as reference
      absorbed dose rate, radial dose function, and one-dimensional (1D) and two
      dimensional (2D) anisotropy functions, were obtained. The computational results
      from these three codes are in agreement within 5.4% difference on average. The
      absorbed dose rate at the reference point was estimated to be 5.01 cGy h-1 MUCi-1
      and self absorption of YAS glass seed amounted to 30.51%. The results showed
      that, with thermal neutron bombardment of 5 hours in a typical flux, sufficient
      activity for applications in brachytherapy may be achieved. With a 5 mCi initial
      activity, the total dose of a YAS glass seed was estimated to be 1.38 Gy at 1.0
      cm from the seed center. Comparing with gamma emitting seeds, the 90Y seed could
      reduce undesirable doses to adjacent organs, because of the rapid dose falloff of
      beta ray. Because of the high R90 value of 5.5 mm, fewer number of 90Y seeds will
      be required for an interstitial brachytherapy treatment using permanent implant,
      in comparison with other beta-emitting seeds. The results would be helpful in the
      development of the radioactive implants using 90Y glass seeds for the
      brachytherapy treatment. 

PMID- 24036863
TI  - A feasibility study using TomoDirect for craniospinal irradiation.
AB  - The feasibility of delivering craniospinal irradiation (CSI) with TomoDirect is
      investigated. A method is proposed to generate TomoDirect plans using standard
      three-dimensional (3D) beam arrangements on Tomotherapy with junctioning of these
      fields to minimize hot or cold spots at the cranial/spinal junction. These plans
      are evaluated and compared to a helical Tomotherapy and a three-dimensional
      conformal therapy (3D CRT) plan delivered on a conventional linear accelerator
      (linac) for CSI. The comparison shows that a TomoDirect plan with an overlap
      between the cranial and spinal fields might be preferable over Tomotherapy plans
      because of decreased low dose to large volumes of normal tissues outside of the
      planning target volume (PTV). Although the TomoDirect plans were not
      dosimetrically superior to a 3D CRT linac plan, the patient can be easily treated
      in the supine position, which is often more comfortable and efficient from an
      anesthesia standpoint. TomoDirect plans also have only one setup position which
      obviates the need for matching of fields and feathering of junctions, two issues
      encountered with conventional 3D CRT plans. TomoDirect plans can be delivered
      with comparable treatment times to conventional 3D plans and in shorter times
      than a Tomotherapy plan. In this paper, a method is proposed for creating
      TomoDirect craniospinal plans, and the dosimetric consequences for choosing
      different planning parameters are discussed. 

PMID- 24036864
TI  - Total skin electron therapy in the lying-on-the-floor position using a customized
      flattening filter to eliminate field junctions.
AB  - A total skin electron (TSE) floor technique is presented for treating patients
      who are unable to safely stand for extended durations. A customized flattening
      filter is used to eliminate the need for field junctioning, improve field
      uniformity, and reduce setup time. The flattening filter is constructed from
      copper and polycarbonate, fits into the linac's accessory slot, and is optimized
      to extend the useful height and width of the beam such that no field junctions
      are needed during treatment. A TSE floor with flattening filter (TSE FF)
      treatment course consisted of six patient positions: three supine and three
      prone. For all treatment fields, electron beam energy was 6 MeV; collimator
      settings were an x of 30 cm, y of 40 cm, and thetacoll of 0 degrees ; and a 0.4
      cm thick polycarbonate spoiler was positioned in front of the patient. Percent
      depth dose (PDD) and photon contamination for the TSE FF technique were compared
      with our standard technique, which is similar to the Stanford technique. Beam
      profiles were measured using radiochromic film, and dose uniformity was verified
      using an anthropomorphic radiological phantom. The TSE FF technique met field
      uniformity requirements specified by the American Association of Physicists in
      Medicine Task Group 30. TSE FF R80 ranges from 4 to 4.8 mm. TSE FF photon
      contamination was ~ 3%. Anthropomorphic radiological phantom verification
      demonstrated that dose to the entire skin surface was expected to be within about
      +/-15% of the prescription dose, except for the perineum, scalp vertex, top of
      shoulder, and soles of the feet. The TSE floor technique presented herein
      eliminates field junctioning, is suitable for patients who cannot safely stand
      during treatment, and provides comparable quality and uniformity to the Stanford
      technique. 

PMID- 24036865
TI  - Influence of different dose calculation algorithms on the estimate of NTCP for
      lung complications.
AB  - Due to limitations and uncertainties in dose calculation algorithms, different
      algorithms can predict different dose distributions and dose-volume histograms
      for the same treatment. This can be a problem when estimating the normal tissue
      complication probability (NTCP) for patient-specific dose distributions.
      Published NTCP model parameters are often derived for a different dose
      calculation algorithm than the one used to calculate the actual dose
      distribution. The use of algorithm-specific NTCP model parameters can prevent
      errors caused by differences in dose calculation algorithms. The objective of
      this work was to determine how to change the NTCP model parameters for lung
      complications derived for a simple correction-based pencil beam dose calculation
      algorithm, in order to make them valid for three other common dose calculation
      algorithms. NTCP was calculated with the relative seriality (RS) and Lyman
      Kutcher-Burman (LKB) models. The four dose calculation algorithms used were the
      pencil beam (PB) and collapsed cone (CC) algorithms employed by Oncentra, and the
      pencil beam convolution (PBC) and anisotropic analytical algorithm (AAA) employed
      by Eclipse. Original model parameters for lung complications were taken from four
      published studies on different grades of pneumonitis, and new algorithm-specific
      NTCP model parameters were determined. The difference between original and new
      model parameters was presented in relation to the reported model parameter
      uncertainties. Three different types of treatments were considered in the study:
      tangential and locoregional breast cancer treatment and lung cancer treatment.
      Changing the algorithm without the derivation of new model parameters caused
      changes in the NTCP value of up to 10 percentage points for the cases studied.
      Furthermore, the error introduced could be of the same magnitude as the
      confidence intervals of the calculated NTCP values. The new NTCP model parameters
      were tabulated as the algorithm was varied from PB to PBC, AAA, or CC. Moving
      from the PB to the PBC algorithm did not require new model parameters; however,
      moving from PB to AAA or CC did require a change in the NTCP model parameters,
      with CC requiring the largest change. It was shown that the new model parameters
      for a given algorithm are different for the different treatment types. 

PMID- 24036866
TI  - Quantifying variability of intrafractional target motion in stereotactic body
      radiotherapy for lung cancers.
AB  - In lung stereotactic body radiotherapy (SBRT), variability of intrafractional
      target motion can negate the potential benefits of four-dimensional (4D)
      treatment planning that aims to account for the dosimetric impacts of organ
      motion. This study used tumor motion data obtained from CyberKnife SBRT
      treatments to quantify the reproducibility of probability motion function (pmf)
      of 37 lung tumors. The reproducibility of pmf was analyzed with and without
      subtracting the intrafractional baseline drift from the original motion data.
      Statistics of intrafractional tumor motion including baseline drift, target
      motion amplitude and period, were also calculated. The target motion amplitude
      significantly correlates with variations (1SD) of motion amplitude and baseline
      drift. Significant correlation between treatment time and variations (1 SD) of
      motion amplitude was observed in anterior-posterior (AP) motion, but not in
      craniocaudal (CC) and left-right (LR) motion. The magnitude of AP and LR baseline
      drifts significantly depend on the treatment time, while the CC baseline drift
      does not. The reproducibility of pmf as a function of time can be well described
      by a two-exponential function with a fast and slow component. The reproducibility
      of pmf is over 60% for the CC motion and over 50% for the AP and LR motions when
      baseline variations were subtracted from the original motion data. It decreases
      to just over 30% for the CC motion and about 20% for the AP and LR motion,
      otherwise. 4D planning has obvious limitations due to variability of
      intrafractional target motion. To account for potential risks of overdosing
      critical organs, it is important to simulate the dosimetric impacts of intra- and
      interfractional baseline drift using population statistics obtained from SBRT
      treatments. 

PMID- 24036867
TI  - CRT combined with a sequential VMAT boost in the treatment of upper thoracic
      esophageal cancer.
AB  - The purpose of this study is to investigate the potential benefits of conformal
      radiotherapy (CRT) combined with a sequential volumetric-modulated arc therapy
      (VMAT) boost in the treatment of upper thoracic esophageal cancer. Ten patients
      with upper thoracic esophageal cancer previously treated with CRT plus a
      sequential VMAT boost plan were replanned with CRT plus an off-cord CRT boost
      plan and a full course of VMAT plan. Dosimetric parameters were compared. Results
      indicated that CRT plus off-cord CRT boost was inferior in planning target volume
      (PTV) coverage, as indicated by the volume covered by 93% (p = 0.05) and 95% (p =
      0.02) of the prescription dose. The full course VMAT plan was superior in
      conformal index (CI) and conformation number (CN), and produced the highest
      protection for the spinal cord. CRT plus a VMAT boost demonstrated significant
      advantages in decreasing the volume of the lung irradiated by a dose of 10 Gy
      (V10, p = 0.007), 13 Gy (V13, p = 0.003), and 20 Gy (V20, p = 0.001). The full
      course VMAT plan demonstrated the lowest volume of lung receiving a dose of 30
      Gy. CRT plus a VMAT boost for upper thoracic esophageal cancer can improve the
      target coverage and reduce the volume of lung irradiated by an intermediate dose.
      This combination may be a promising treatment technique for patients with upper
      thoracic esophageal cancer. 

PMID- 24036868
TI  - Application of failure mode and effects analysis (FMEA) to pretreatment phases in
      tomotherapy.
AB  - The aim of this paper was the application of the failure mode and effects
      analysis (FMEA) approach to assess the risks for patients undergoing radiotherapy
      treatments performed by means of a helical tomotherapy unit. FMEA was applied to
      the preplanning imaging, volume determination, and treatment planning stages of
      the tomotherapy process and consisted of three steps: 1) identification of the
      involved subprocesses; 2) identification and ranking of the potential failure
      modes, together with their causes and effects, using the risk probability number
      (RPN) scoring system; and 3) identification of additional safety measures to be
      proposed for process quality and safety improvement. RPN upper threshold for
      little concern of risk was set at 125. A total of 74 failure modes were
      identified: 38 in the stage of preplanning imaging and volume determination, and
      36 in the stage of planning. The threshold of 125 for RPN was exceeded in four
      cases: one case only in the phase of preplanning imaging and volume
      determination, and three cases in the stage of planning. The most critical
      failures appeared related to (i) the wrong or missing definition and contouring
      of the overlapping regions, (ii) the wrong assignment of the overlap priority to
      each anatomical structure, (iii) the wrong choice of the computed tomography
      calibration curve for dose calculation, and (iv) the wrong (or not performed)
      choice of the number of fractions in the planning station. On the basis of these
      findings, in addition to the safety strategies already adopted in the clinical
      practice, novel solutions have been proposed for mitigating the risk of these
      failures and to increase patient safety. 

PMID- 24036869
TI  - Improving plan quality and consistency by standardization of dose constraints in
      prostate cancer patients treated with CyberKnife.
AB  - Treatment plans for prostate cancer patients undergoing stereotactic body
      radiation therapy (SBRT) are often challenging due to the proximity of organs at
      risk. Today, there are no objective criteria to determine whether an optimal
      treatment plan has been achieved, and physicians rely on their personal
      experience to evaluate the plan's quality. In this study, we propose a method for
      determining rectal and bladder dose constraints achievable for a given patient's
      anatomy. We expect that this method will improve the overall plan quality and
      consistency, and facilitate comparison of clinical outcomes across different
      institutions. The 3D proximity of the organs at risk to the target is quantified
      by means of the expansion-intersection volume (EIV), which is defined as the
      intersection volume between the target and the organ at risk expanded by 5 mm. We
      determine a relationship between EIV and relevant dosimetric parameters, such as
      the volume of bladder and rectum receiving 75% of the prescription dose (V75%).
      This relationship can be used to establish institution-specific criteria to guide
      the treatment planning and evaluation process. A database of 25 prostate patients
      treated with CyberKnife SBRT is used to validate this approach. There is a linear
      correlation between EIV and V75% of bladder and rectum, confirming that the dose
      delivered to rectum and bladder increases with increasing extension and proximity
      of these organs to the target. This information can be used during the planning
      stage to facilitate the plan optimization process, and to standardize plan
      quality and consistency. We have developed a method for determining customized
      dose constraints for prostate patients treated with robotic SBRT. Although the
      results are technology specific and based on the experience of a single
      institution, we expect that the application of this method by other institutions
      will result in improved standardization of clinical practice. 

PMID- 24036870
TI  - Gemstone spectral imaging: determination of CT to ED conversion curves for
      radiotherapy treatment planning.
AB  - The monochromatic images acquired by Gemstone spectral imaging (GSI) mode on the
      GE CT750 HD theoretically determines the computed tomography (CT) number more
      accurately than that of conventional scanner. Using the former, the CT number is
      calculated from (synthesized) monoenergetic X-ray data. We reasoned that the
      monochromatic image might be applied to radiotherapy treatment planning (RTP) to
      calculate dose distribution more accurately. Our goal here was to provide CT to
      electron density (ED) conversion curves with monochromatic images for RTP.
      Therefore, we assessed the reproducibility of CT numbers, an important factor on
      quality assurance, over short and long time periods for different substances at
      varying energy. CT number difference between measured and theoretical value was
      investigated. The scanner provided sufficient reproducibility of CT numbers for
      dose calculation over short and long time periods. The CT numbers of
      monochromatic images produced by this scanner had reasonable values for dose
      calculation. The CT to ED conversion curve becomes linear with respect to the
      relationship between CT numbers and EDs as the energy increases. We conclude that
      monochromatic imaging from a fast switching system can be applied for the dose
      calculation, keeping Hounsfield units (HU) stability. 

PMID- 24036871
TI  - Stability of percutaneously implanted markers for lung stereotactic radiotherapy.
AB  - The purpose of this study was to evaluate the stability of complex markers
      implanted into lung tumors throughout a course of stereotactic body radiotherapy
      (SBRT). Fifteen patients referred for lung SBRT were prospectively included.
      Radio-opaque markers were implanted percutaneously, guided by computed tomography
      (CT). Deep inspiration breath-hold CT scans (BHCT) were acquired at planning and
      on three treatment days. The treatment days' BHCTs were registered to the
      planning BHCT. Intraobserver uncertainty in both tumor and marker registration
      was determined. Deviations in the difference between tumor and marker-based image
      registrations of the BHCT scans during treatment quantified the marker stability.
      Marker position deviation relative to tumor position of less than 2 mm in all
      three dimensions was considered acceptable for treatment delivery precision.
      Intra observer uncertainties for image registration in the left-right (LR),
      anterior-posterior (AP), craniocaudal (CC) directions and three-dimensional
      vector (3D) were 0.9 mm, 0.9 mm, 1.0 mm, and 1.1 mm (SD) for tumor registration
      and 0.3 mm, 0.5 mm, 0.7 mm, and 0.7 mm (SD) for marker registration. Mean 3D
      differences for tumor registrations on all days were significantly larger than
      for 3D marker registrations (p = 0.007). Overall median differences between tumor
      and marker position were 0.0 mm (range -2.9 to 2.6 mm) in LR, 0.0 mm (-1.8 to 1.5
      mm) in AP, and -0.2 mm (-2.6 to 2.8 mm) in CC directions. Four patients had
      deviations exceeding 2 mm in one or more registrations throughout the SBRT
      course. This is the first study to evaluate stability of complex markers
      implanted percutaneously into lung tumors for image guidance in SBRT. We conclude
      that the observed stability of marker position within the tumor indicates that
      complex markers can be used as surrogates for tumor position during a short
      course of SBRT as long as the uncertainties related to their position within the
      tumor are incorporated into the planning target volume. 

PMID- 24036872
TI  - Equivalent square formula for determining the surface dose of rectangular field
      from 6 MV therapeutic photon beam.
AB  - The purpose of the study was to investigate the use of the equivalent square
      formula for determining the surface dose from a rectangular photon beam. A 6 MV
      therapeutic photon beam delivered from a Varian Clinac 23EX medical linear
      accelerator was modeled using the EGS4nrc Monte Carlo simulation package. It was
      then used to calculate the dose in the build-up region from both square and
      rectangular fields. The field patterns were defined by various settings of the X-
      and Y-collimator jaw ranging from 5 to 20 cm. Dose measurements were performed
      using a thermoluminescence dosimeter and a Markus parallel-plate ionization
      chamber on the four square fields (5 * 5, 10 * 10, 15 * 15, and 20 * 20 cm2). The
      surface dose was acquired by extrapolating the build-up doses to the surface. An
      equivalent square for a rectangular field was determined using the area-to
      perimeter formula, and the surface dose of the equivalent square was estimated
      using the square-field data. The surface dose of square field increased linearly
      from approximately 10% to 28% as the side of the square field increased from 5 to
      20 cm. The influence of collimator exchange on the surface dose was found to be
      not significant. The difference in the percentage surface dose of the rectangular
      field compared to that of the relevant equivalent square was insignificant and
      can be clinically neglected. The use of the area-to-perimeter formula for an
      equivalent square field can provide a clinically acceptable surface dose
      estimation for a rectangular field from a 6 MV therapy photon beam. 

PMID- 24036873
TI  - Collision indicator charts for gantry-couch position combinations for Siemens
      ONCOR and Elekta Infinity linacs.
AB  - Noncoplanar radiation fields from a linear accelerator can be used to deliver
      radiation dose distributions that are superior to those delivered using coplanar
      radiation fields. Noncoplanar radiation field arrangements are especially
      valuable when delivering stereotactic body radiation therapy (SBRT). Noncoplanar
      radiation fields, however, are geometrically more challenging to deliver than
      coplanar radiation fields, and are associated with a greater risk of collisions
      between the gantry, treatment couch, and patient. Knowledge of which treatment
      couch offset, treatment couch angle, and gantry angle combinations provide a
      collision-free radiotherapy delivery is useful in the treatment planning process,
      as the risk of requiring replanning due to improperly selected treatment
      parameters can be minimized. Such tables are by default specific to the linear
      accelerator make and model used for treatment. In this work a set of plots is
      presented indicating which combination of treatment couch lateral offsets (-10 cm
      to 10 cm), couch angles (270 degrees  to 90 degrees ), and gantry angles (0
      degrees  to 360 degrees ), will result in collision-free radiation delivery using
      Siemens ONCOR linear accelerators equipped with a 160-leaf multileaf collimator
      and a 550 TxT treatment table, and a Elekta Infinity linear accelerator with an
      MLCi2 and Elekta iBEAM evo Couchtop EP. The patient was assumed to have a width
      of 50 cm and a height of 25 cm. 

PMID- 24036874
TI  - Reducing excess radiation from portal imaging of pediatric brain tumors.
AB  - Previously we have shown that our routine portal imaging (PI) of the craniofacial
      region in pediatric brain tumor patients contributed an additional 2%-3% of the
      prescribed dose and up to 200 cGy to the planning target volume (PTV) and nearby
      organs at risk (OARs). The purpose of this study is to quantify the reduction in
      dose to PTV and OARs from portal imaging (PI) of the craniofacial region of
      pediatric patients treated after the implementation of changes in our portal
      imaging practices. Twenty consecutive pediatric patients were retrospectively
      studied since the implementation of changes to our portal imaging procedure. Each
      received portal imaging of treatment fields and orthogonal setup fields to the
      craniofacial region. PI modifications included a reduction in the field size of
      setup orthogonal fields without loss of radiographic information needed for
      treatment verification. In addition, treatment fields were imaged using a single
      exposure, rather than double exposure. Dose-volume histograms were generated to
      quantify the dose to the target and critical structures through PI acquisition.
      These results were compared with our previous cohort of 20 patients who were
      treated using the former portal imaging practices. The mean additional target
      dose from portal imaging following the new guidelines was 1.5% of the prescribed
      dose compared to 2.5% prior to the new portal image practices (p < 0.001). With
      the new portal imaging practices, the percentage decrease in portal imaging dose
      to the brainstem, optic structures, cochlea, hypothalamus, temporal lobes,
      thyroid, and eyes were 25%, 35%, 35%, 51%, 45%, 80%, and 55%, respectively.
      Reductions in portal imaging doses were significant in all OARs with exception of
      the brainstem, which showed a trend towards significance. Changes to portal
      imaging practices can reduce the radiation dose contribution from portal imaging
      to surrounding OARs by up to 80%. This may have implications on both late
      toxicity and second cancer development in pediatric brain tumors. 

PMID- 24036875
TI  - Patient dosimetry for 90Y selective internal radiation treatment based on 90Y PET
      imaging.
AB  - Until recently, the radiation dose to patients undergoing the 90Y selective
      internal radiation treatment (SIRT) procedure is determined by applying the
      partition model to 99mTc MAA pretreatment scan. There can be great uncertainty in
      radiation dose calculated from this approach and we presented a method to compute
      the 3D dose distributions resulting from 90Y SIRT based on 90Y positron emission
      tomography (PET) imaging. Five 90Y SIRT treatments were retrospectively analyzed.
      After 90Y SIRT, patients had 90Y PET/CT imaging within 6 hours of the procedure.
      To obtain the 3D dose distribution of the patients, their respective 90Y PET
      images were convolved with a Monte Carlo generated voxel dose kernel. The
      sensitivity of the PET/CT scanner for 90Y was determined through phantom studies.
      The 3D dose distributions were then presented in DICOM RT dose format. By
      applying the linear quadratic model to the dose data, we derived the biologically
      effective dose and dose equivalent to 2 Gy/fraction delivery, taking into account
      the spatial and temporal dose rate variations specific for SIRT. Based on this
      data, we intend to infer tumor control probability and risk of radiation induced
      liver injury from SIRT by comparison with established dose limits. For the five
      cases, the mean dose to target ranged from 51.7 +/- 28.6 Gy to 163 +/- 53.7 Gy.
      Due to the inhomogeneous nature of the dose distribution, the GTVs were not
      covered adequately, leading to very low values of tumor control probability. The
      mean dose to the normal liver ranged from 21.4 +/- 30.7 to 36.7 +/- 25.9 Gy.
      According to QUANTEC recommendation, a patient with primary liver cancer and a
      patient with metastatic liver cancer has more than 5% risk of radiotherapy
      induced liver disease (RILD). 

PMID- 24036876
TI  - Hierarchical enhanced non-rigid registration for target volume correction and
      propagation for adaptive external beam radiotherapy of carcinoma of the prostate.
AB  - Volumes change during fractionated radiotherapy (RT). We investigate a tool based
      on the Hierarchical Enhanced Registration Algorithm (HERA) to project a 3D
      segmentation set of the prostate into the subsequent imaging sets at any time
      point during RT by using intensity-based image registration techniques.
      Sequential CT sets during RT at 15, 30, 45, and 60 Gy of two patients were used.
      Five expert clinicians outlined the prostate in a blinded fashion, defining
      intraobserver and interobserver variability on a set of 35 and 25 scans,
      respectively. The observer variability and positioning for manual correction was
      compared to both affine and elastic image registration-based contour propagation.
      The overall mean error of the registration-based correction of the planning
      target volume was comparable to the interobserver variability of manual target
      volume definition. The correction by affine image fusion was inferior to the
      results of elastic registration. The maximal deviation for the interobserver
      segmentation was 15.4 mm, 10.5 mm for the affine and 8.0 mm for the elastic
      registration. The mean interobserver variability was 1.5 (+/- 1.4) mm, 2.8 (+/-
      2.3) mm for the affine, and 2.2 (+/- 1.9) mm for the elastic registration.
      Intensity-based elastic registration of deformable anatomical structures with
      HERA is suitable for the assessment of changes of prostate volumes for the
      purpose of target propagation and adaptive radiotherapy. 

PMID- 24036877
TI  - Dosimetric characterization and optimization of a customized Stanford total skin
      electron irradiation (TSEI) technique.
AB  - Total skin electron irradiation (TSEI) has been used as a treatment for mycosis
      fungoides. Our center has implemented a modified Stanford technique with six
      pairs of 6 MeV adjacent electron beams, incident perpendicularly on the patient
      who remains lying on a translational platform, at 200 cm from the source. The
      purpose of this study is to perform a dosimetric characterization of this
      technique and to investigate its optimization in terms of energy characteristics,
      extension, and uniformity of the treatment field. In order to improve the
      homogeneity of the distribution, a custom-made polyester filter of variable
      thickness and a uniform PMMA degrader plate were used. It was found that the
      characteristics of a 9 MeV beam with an 8 mm thick degrader were similar to those
      of the 6 MeV beam without filter, but with an increased surface dose. The
      combination of the degrader and the polyester filter improved the uniformity of
      the distribution along the dual field (180cm long), increasing the dose at the
      borders of field by 43%. The optimum angles for the pair of beams were +/- 27
      degrees . This configuration avoided displacement of the patient, and reduced the
      treatment time and the positioning problems related to the abutting superior and
      inferior fields. Dose distributions in the transversal plane were measured for
      the six incidences of the Stanford technique with film dosimetry in an
      anthropomorphic pelvic phantom. This was performed for the optimized treatment
      and compared with the previously implemented technique. The comparison showed an
      increased superficial dose and improved uniformity of the 85% isodose curve
      coverage for the optimized technique. 

PMID- 24036878
TI  - Migration from full-head mask to "open-face" mask for immobilization of patients
      with head and neck cancer.
AB  - To provide an alternative device for immobilization of the head while easing
      claustrophobia and improving comfort, an "open-face" thermoplastic mask was
      evaluated using video-based optical surface imaging (OSI) and kilovoltage (kV) X
      ray radiography. A three-point thermoplastic head mask with a precut opening and
      reinforced strips was developed. After molding, it provided sufficient visible
      facial area as the region of interest for OSI. Using real-time OSI, the head
      motion of ten volunteers in the new mask was evaluated during mask locking and
      15minutes lying on the treatment couch. Using a nose mark with reference to room
      lasers, forced head movement in open-face and full-head masks (with a nose hole)
      was compared. Five patients with claustrophobia were immobilized with open-face
      masks, set up using OSI and kV, and treated in 121 fractions, in which 61
      fractions were monitored during treatment using real-time OSI. With the open-face
      mask, head motion was found to be 1.0 +/- 0.6 mm and 0.4 degrees  +/- 0.2 degrees
      in volunteers during the experiment, and 0.8 +/- 0.3 mm and 0.4 degrees  +/- 0.2
      degrees  in patients during treatment. These agree with patient motion calculated
      from pre-/post-treatment OSI and kV data using different anatomical landmarks. In
      volunteers, the head shift induced by mask-locking was 2.3 +/- 1.7 mm and 1.8
      degrees  +/- 0.6 degrees , and the range of forced movements in the open-face and
      full-head masks were found to be similar. Most (80%) of the volunteers preferred
      the open-face mask to the full-head mask, while claustrophobic patients could
      only tolerate the open-face mask. The open-face mask is characterized for its
      immobilization capability and can immobilize patients sufficiently (< 2 mm)
      during radiotherapy. It provides a clinical solution to the immobilization of
      patients with head and neck (HN) cancer undergoing radiotherapy, and is
      particularly beneficial for claustrophobic patients. This new open-face mask is
      readily adopted in radiotherapy clinic as a superior alternative to the standard
      full-head mask. 

PMID- 24036879
TI  - AAPM medical physics practice guideline 1.a: CT protocol management and review
      practice guideline.

PMID- 24036880
TI  - Effect of audio instruction on tracking errors using a four-dimensional image
      guided radiotherapy system.
AB  - The Vero4DRT (MHI-TM2000) is capable of performing X-ray image-based tracking (X
      ray Tracking) that directly tracks the target or fiducial markers under
      continuous kV X-ray imaging. Previously, we have shown that irregular respiratory
      patterns increased X-ray Tracking errors. Thus, we assumed that audio
      instruction, which generally improves the periodicity of respiration, should
      reduce tracking errors. The purpose of this study was to assess the effect of
      audio instruction on X-ray Tracking errors. Anterior-posterior abdominal skin
      surface displacements obtained from ten lung cancer patients under free breathing
      and simple audio instruction were used as an alternative to tumor motion in the
      superior-inferior direction. First, a sequential predictive model based on the
      Levinson-Durbin algorithm was created to estimate the future three-dimensional
      (3D) target position under continuous kV X-ray imaging while moving a steel ball
      target of 9.5 mm in diameter. After creating the predictive model, the future 3D
      target position was sequentially calculated from the current and past 3D target
      positions based on the predictive model every 70 ms under continuous kV X-ray
      imaging. Simultaneously, the system controller of the Vero4DRT calculated the
      corresponding pan and tilt rotational angles of the gimbaled X-ray head, which
      then adjusted its orientation to the target. The calculated and current
      rotational angles of the gimbaled X-ray head were recorded every 5 ms. The target
      position measured by the laser displacement gauge was synchronously recorded
      every 10 msec. Total tracking system errors (ET) were compared between free
      breathing and audio instruction. Audio instruction significantly improved
      breathing regularity (p < 0.01). The mean +/- standard deviation of the 95th
      percentile of ET (E95T ) was 1.7 +/- 0.5 mm (range: 1.1-2.6mm) under free
      breathing (E95T,FB) and 1.9 +/- 0.5 mm (range: 1.2-2.7 mm) under audio
      instruction (E95T,AI). E95T,AI was larger than E95T,FB for five patients; no
      significant difference was found between E95T,FB and E95T,AI (p = 0.21).
      Correlation analysis revealed that the rapid respiratory velocity significantly
      increased E95T. Although audio instruction improved breathing regularity, it also
      increased the respiratory velocity, which did not necessarily reduce tracking
      errors. 

PMID- 24036881
TI  - The future of medical physics in the US health-care system.

PMID- 24036882
TI  - The retinol esterifying enzyme LRAT supports cell signaling by retinol-binding
      protein and its receptor STRA6.
AB  - Vitamin A, retinol, circulates in blood bound to retinol-binding protein (RBP).
      At some tissues, holo-RBP is recognized by a plasma membrane receptor termed
      STRA6, which serves a dual role: it mediates transport of retinol from RBP into
      cells, and it functions as a cytokine receptor that, on binding holo-RBP,
      activates JAK2/STAT5 signaling. As STAT target genes include SOCS3, an inhibitor
      of insulin receptor, holo-RBP suppresses insulin responses in STRA6-expressing
      cells. We have shown previously that the two functions of STRA6 are
      interdependent. These observations suggest factors that regulate STRA6-mediated
      retinol transport may also control STRA6-mediated cell signaling. One such factor
      is retinol metabolism, which enables cellular uptake of retinol by maintaining an
      inward-directed concentration gradient. We show here that lecithin:retinol acyl
      transferase (LRAT), which catalyzes esterification of retinol to its storage
      species retinyl esters, is necessary for activation of the STRA6/JAK2/STAT5
      cascade by holo-RBP. In accordance, LRAT-null mice are protected from holo-RBP
      induced suppression of insulin responses. Hence, STRA6 signaling, which requires
      STRA6-mediated retinol transport, is supported by LRAT-catalyzed retinol
      metabolism. The observations demonstrate that STRA6 regulates key cellular
      processes by coupling circulating holo-RBP levels and intracellular retinol
      metabolism to cell signaling.

PMID- 24036883
TI  - Dosage of amyloid precursor protein affects axonal contact guidance in Down
      syndrome.
AB  - Amyloid precursor protein (APP), encoded on Hsa21, functions as a cell adhesion
      molecule (CAM) in axonal growth cones (GCs) of the developing brain. We show here
      that axonal GCs of human fetal Down syndrome (DS) neurons (and of a DS mouse
      model) overexpress APP protein relative to euploid controls. We investigated
      whether DS neurons generate an abnormal, APP-dependent GC phenotype in vitro. On
      laminin, which binds APP and beta1 integrins (Itgb1), DS neurons formed enlarged
      and faster-advancing GCs compared to controls. On peptide matrices that bind APP
      only, but not on those binding exclusively Itgb1 or L1CAM, DS GCs were
      significantly enlarged (2.0-fold), formed increased close adhesions (1.8-fold),
      and advanced faster (1.4-fold). In assays involving alternating stripes of
      monospecific matrices, human control GCs exhibited no preference for any of the
      substrates, whereas DS GCs preferred the APP-binding matrix (cross-over decreased
      significantly from 48.2 to 27.2%). Reducing APP expression in DS GCs with siRNA
      normalized most measures of the phenotype, including substrate choice. These
      experiments show that human DS neurons exhibit an APP-dependent, abnormal GC
      phenotype characterized by increased adhesion and altered contact guidance. The
      results suggest that APP overexpression may perturb axonal pathfinding and
      circuit formation in developing DS brain.

PMID- 24036884
TI  - Localization of relaxin receptors in arteries and veins, and region-specific
      increases in compliance and bradykinin-mediated relaxation after in vivo
      serelaxin treatment.
AB  - Relaxin is a potent vasodilator of small resistance arteries and modifies
      arterial compliance in some systemic vascular beds, yet receptors for relaxin,
      such as RXFP1, have only been localized to vascular smooth muscle. This study
      first aimed to localize RXFP1 in rat arteries and veins from different organ beds
      and determine whether receptors are present in endothelial cells. We then tested
      the hypothesis that region-specific vascular effects of relaxin may be influenced
      by the cellular localization of RXFP1 within different blood vessels. The aorta,
      vena cava, mesenteric artery, and vein had significantly higher (P<0.05) RXFP1
      immunostaining in endothelial cells compared with vascular smooth muscle, whereas
      the femoral artery and vein and small pulmonary arteries had higher (P<0.01)
      RXFP1 immunostaining in the vascular smooth muscle. Male rats were treated
      subcutaneously with recombinant human relaxin-2 (serelaxin; 4 MUg/h) for 5 d;
      vasodilation and compliance in mesenteric and femoral arteries and veins were
      compared with placebo controls. Serelaxin significantly (P=0.04) reduced wall
      stiffness and increased volume compliance in mesenteric arteries but not in the
      other vessels examined. This was associated with changes in geometrical
      properties, and not compositional changes in the extracellular matrix. Serelaxin
      treatment had no effect on acetylcholine-mediated relaxation but significantly
      (P<0.001) enhanced bradykinin (BK)-mediated relaxation in mesenteric arteries,
      involving enhanced nitric oxide but not endothelium-derived hyperpolarization or
      vasodilatory prostanoids. In conclusion, there is differential distribution of
      RXFP1 on endothelial and smooth muscle across the vasculature. In rats,
      mesenteric arteries exhibit the greatest functional response to chronic serelaxin
      treatment.

PMID- 24036885
TI  - The endolysosomal cysteine cathepsins L and K are involved in macrophage-mediated
      clearance of Staphylococcus aureus and the concomitant cytokine induction.
AB  - Cysteine cathepsins are endolysosomal cysteine proteases highly expressed in
      macrophages; however, their individual contributions to the elimination of
      bacteria and bacteria-induced cytokine production by macrophages are unknown. We
      assessed the contribution of cysteine cathepsins to macrophage defense pathways
      against Staphylococcus aureus by using chemical inhibitors and by infecting
      primary bone marrow-derived macrophages deficient in 1 of 7 major macrophage
      expressed endolysosomal cysteine proteases. We show that cysteine cathepsins are
      involved in the phagocytosis and killing of S. aureus. Cathepsin L was identified
      as an executor of nonoxidative killing. Moreover, microarray data revealed
      cysteine cathepsins to be important for the maximal induction of certain
      proinflammatory genes, such as IL6, in response to S. aureus. Cysteine
      cathepsin's contribution to IL6 production was dependent on phagocytosis, and
      cathepsin K was identified to be a critical protease in this process. Analysis of
      macrophages with impaired trafficking of endolysosomal Toll-like receptors (TLRs)
      to the acidic compartment revealed that they were not involved in cathepsin
      dependent IL6 induction. Because IL6 production was completely dependent on the
      TLR-adaptor protein myeloid differentiation primary response gene 88 (MyD88), it
      appears that other TLRs are involved. In summary, lysosomal cysteine proteases
      are functionally linked to the complex bactericidal and inflammatory activities
      of macrophages.

PMID- 24036886
TI  - Structural characterization of a fusion glycoprotein from a retrovirus that
      undergoes a hybrid 2-step entry mechanism.
AB  - Entry of enveloped viruses into host cells is mediated by their surface envelope
      glycoproteins (Env). On the surface of the virus, Env is in a metastable,
      prefusion state, primed to catalyze the fusion of the viral and host membranes.
      An external trigger is needed to promote the drastic conformational changes
      necessary for the fusion subunit to fold into the low-energy, 6-helix bundle.
      These triggers typically facilitate pH-independent entry at the plasma membrane
      or pH-dependent entry in a low-pH endosomal compartment. The alpha-retrovirus
      avian sarcoma leukosis virus (ASLV) has a rare, 2-step entry mechanism with both
      pH-dependent and pH-independent features. Here, we present the 2.0-A-resolution
      crystal structure of the ASLV transmembrane (TM) fusion protein. Our structural
      and biophysical studies indicated that unlike other pH-dependent or pH
      independent viral TMs, the ASLV fusion subunit is stable irrespective of pH. Two
      histidine residues (His490 and His492) in the chain reversal region confer
      stability at low pH. A structural comparison of class I viral fusion proteins
      suggests that the presence of a positive charge, either a histidine or arginine
      amino acid, stabilizes a helical dipole moment and is a signature of fusion
      proteins active at low pH. The structure now reveals key residues and features
      that explain its 2-step mechanism, and we discuss the implications of the ASLV TM
      structure in the context of general mechanisms required for membrane fusion.

PMID- 24036887
TI  - Stump sensibility in children with upper limb reduction deficiency.
AB  - OBJECTIVES: To compare stump sensibility in children with upper limb reduction
      deficiency with sensibility of the unaffected arm and hand. In addition, to
      evaluate the associations between stump sensibility, stump length and activity
      level. DESIGN: Cross-sectional study. SUBJECTS: Children and young adults aged 6
      25 years with upper limb reduction deficiency. METHODS: Threshold of touch was
      measured with Semmes-Weinstein monofilaments, stereognosis was measured with the
      Shape-Texture Identification test and kinaesthesia and activity level was
      measured with the Child Amputee Prosthetics Project - Functional Status Inventory
      and the Prosthetic Upper Extremity Functional Index. RESULTS: A total of 31
      children with upper limb reduction deficiency (mean age 15 years, 3 prosthesis
      wearers) were investigated. The threshold of touch of the stump circumference was
      lower (indicating higher sensibility) than of the unaffected arm (p = 0.006),
      hand (p = 0.004) and stump end-point (p = < 0.001). Long stumps had higher
      threshold of touch (indicating lower sensibility) than short stumps (p = 0.046).
      Twenty-nine children recognized 1 or more shapes or textures with the stump.
      Kinaesthesia in the affected and unaffected sides was comparable. Sensibility was
      not correlated with activity level. CONCLUSION: Threshold of touch, stereognosis
      and kinaesthesia of the affected sides were excellent. Threshold of touch of the
      stump circumference was lower (indicating higher sensibility) than of the
      unaffected arm and hand. High stump sensibility may clarify good functioning in
      the children without prostheses and contribute to prosthesis rejection.

PMID- 24036888
TI  - Discoidin domain receptor 2 (DDR2) regulates body size and fat metabolism in
      mice.
AB  - Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is
      activated by fibrillar collagens, which act as its endogenous ligand. DDR2
      regulates cell proliferation, cell adhesion, migration, extracellular matrix
      remodeling and reproductive functions. Both DDR2 null allele mice and mice with a
      recessive, loss-of-function allele for Ddr2 exhibit dwarfing and a reduction in
      body weight. However, the detailed mechanisms by which DDR2 exerts its positive
      systemic regulation of whole body size, local skeletal size and fat tissue volume
      remain to be clarified. To investigate the systemic role of DDR2 in body size
      regulation, we produced transgenic mice in which the DDR2 protein is
      overexpressed, then screened the transgenic mice for abnormalities using
      systematic mouse abnormality screening. The modified-SHIPRA screen revealed that
      only the parameter of body size was significantly different among the genotypes.
      We also discovered that the body length was significantly increased, while the
      body weight was significantly decreased in transgenic mice compared to their
      littermate controls. We also found that the epididymal fat pads were
      significantly decreased in transgenic mice compared to normal littermate mice,
      which may have been the cause of the leptin decrement in the transgenic mice. The
      new insight that DDR2 might promote metabolism in adipocyte cells is very
      interesting, but more experiments will be needed to elucidate the direct relation
      between DDR2 and adipose-derived hormones. Taken together, our data demonstrated
      that DDR2 might play a systemic role in the regulation of body size thorough
      skeletal formation and fat metabolism. 

PMID- 24036890
TI  - Cancer survival in Indigenous and non-Indigenous Australian children: what is the
      difference?
AB  - PURPOSE: This study assessed variation in childhood cancer survival by Indigenous
      status in Australia, and explored the effect of place of residence and socio
      economic disadvantage on survival. METHODS: All children diagnosed with cancer
      during 1997-2007 were identified through the Australian Pediatric Cancer
      Registry. Cox regression analysis was used to assess the adjusted differences in
      survival. RESULTS: Overall, 5-years survival was 75.0 % for Indigenous children
      (n = 196) and 82.3 % for non-Indigenous children (n = 6,376, p = 0.008). Compared
      to other children, Indigenous cases had 1.36 times the risk of dying within 5
      years of diagnosis after adjustments for rurality of residence, socio-economic
      disadvantage, cancer diagnostic group, and year of diagnosis (95 % CI 1.01-1.82).
      No significant survival differential was found for leukemias or tumors of the
      central nervous system; Indigenous children were 1.83 times more likely (95 % CI
      1.22-2.74) than other children to die within 5 years from 'other tumors' (e.g.,
      lymphomas, neuroblastoma). Among children who lived in 'remote/very remote/outer
      regional' areas, and among children with a subgroup of 'other tumors' that were
      staged, being Indigenous significantly increased the likelihood of death (HR =
      1.69, 95 % CI 1.10-2.59 and HR = 2.99, 95 % CI 1.35-6.62, respectively); no
      significant differences by Indigenous status were seen among children with stage
      data missing. CONCLUSIONS: Differences in place of residence, socio-economic
      disadvantage, and cancer diagnostic group only partially explain the survival
      disadvantage of Indigenous children. Other reasons underlying the disparities in
      childhood cancer outcomes by Indigenous status are yet to be determined, but may
      involve factors such as differences in treatment.

PMID- 24036889
TI  - Plasma C-reactive protein, genetic risk score, and risk of common cancers in the
      Atherosclerosis Risk in Communities study.
AB  - PURPOSE: Many studies, including the Atherosclerosis Risk in Communities (ARIC)
      cohort, reported a positive association between plasma C-reactive protein (CRP)-a
      biomarker of low-grade chronic inflammation-and colorectal cancer risk, although
      it is unclear whether the association is causal. Our aims were to assess the
      associations of a CRP genetic risk score (CRP-GRS) created from single-nucleotide
      polymorphisms (SNPs) with colorectal cancer risk, as well as examine plasma CRP
      and CRP-GRS in relation to common cancers in the ARIC cohort. METHODS: Cox
      proportional hazards models were used to prospectively estimate hazard ratios
      (HRs) and 95 % confidence interval (95 % CI) of total, colorectal, lung,
      prostate, and breast cancers in relation to: (1) CRP-GRS among 8,657 Whites
      followed in 1987-2006 and (2) log-transformed plasma CRP among 7,603 Whites
      followed in 1996-2006. A weighted CRP-GRS was comprised of 20 CRP-related SNPs
      located in/near CRP, APOC1, HNF1A, LEPR, and 16 other genes that were identified
      in genome-wide association studies. RESULTS: After multivariable adjustment, one
      standard deviation increment of the CRP-GRS was associated with colorectal cancer
      risk (HR 1.19; 95 % CI 1.03-1.37), but not with any other cancer. One unit of log
      transformed plasma CRP was associated with the risk of total, colorectal, lung,
      and breast cancers: HRs (95 % CIs) were 1.08 (1.01-1.15), 1.24 (1.01-1.51), 1.29
      (1.08-1.54), and 1.27 (1.07-1.51), respectively. HRs remained elevated, although
      lost statistical significance for all but breast cancer, after excluding subjects
      with <2 years of follow-up. CONCLUSIONS: The study corroborates a causative role
      of chronic low-grade inflammation in colorectal carcinogenesis.

PMID- 24036892
TI  - Testing the mutant selection window hypothesis with Escherichia coli exposed to
      levofloxacin in a rabbit tissue cage infection model.
AB  - The purpose of this study was to test the mutant selection window (MSW)
      hypothesis with Escherichia coli exposed to levofloxacin in a rabbit model and to
      compare in vivo and in vitro exposure thresholds that restrict the selection of
      fluoroquinolone-resistant mutants. Local infection with E. coli was established
      in rabbits, and the infected animals were treated orally with various doses of
      levofloxacin once a day for five consecutive days. Changes in levofloxacin
      concentration and levofloxacin susceptibility were monitored at the site of
      infection. The MICs of E. coli increased when levofloxacin concentrations at the
      site of infection fluctuated between the lower and upper boundaries of the MSW,
      defined in vitro as the minimum inhibitory concentration (MIC99) and the mutant
      prevention concentration (MPC), respectively. The pharmacodynamic thresholds at
      which resistant mutants are not selected in vivo was estimated as AUC24/MPC > 20
      h or AUC24/MIC > 60 h, where AUC24 is the area under the drug concentration time
      curve in a 24-h interval. Our finding demonstrated that the MSW existed in vivo.
      The AUC24/MPC ratio that prevented resistant mutants from being selected
      estimated in vivo is consistent with that observed in vitro, indicating it might
      be a reliable index for guiding the optimization of antimicrobial treatment
      regimens for suppression of the selection of antimicrobial resistance.

PMID- 24036893
TI  - Occurrence of virulence genes, 16S rRNA methylases, and plasmid-mediated
      quinolone resistance genes in CTX-M-producing Escherichia coli from Pakistan.
AB  - The aim of the study was to conduct a comprehensive molecular characterization of
      extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli collected from
      Pakistan. Genetic relatedness among 98 ESBL-producing E. coli was measured by
      pulsed-field gel electrophoresis (PFGE). The presence of genes encoding ESBLs,
      virulence factors (VFs), 16S rRNA methylases, plasmid-mediated quinolone
      resistance (PMQR) encoding elements, plasmid replicon types, phylogenetic groups
      of E. coli, prevalence of the worldwide disseminated clone E. coli ST131, and
      phylogrouping of CTX-M enzymes was investigated by polymerase chain reaction
      (PCR). All isolates carried bla CTX-M genes and, except for one isolate from CTX
      M phylogroup 9, they all belonged to CTX-M phylogroup 1. The isolates were
      genetically diverse with PFGE. Phylogenetic group D (36 %) was most abundant in
      this collection of E. coli, whereas isolates belonging to B2 (22 %) had the
      highest content of virulence genes. PMQR genes were found in 84.6 % of the
      isolates; among them, 93 % isolates were positive for variants of
      acetyltransferases (aac(6')-lb-cr), whereas qnrB, qepA, and qnrS were present in
      11 %, 5 %, and 4 % of the isolates, respectively. Only 3 % of the isolates
      contained genes encoding 16S rRNA methylases. The most abundant replicon type was
      IncF (96 %), and 18 % of the isolates belonged to the ST131 clone. Out of 34
      investigated VFs, 24 genes encoding different types of adhesins, protectins,
      toxins, siderophores, and other VFs were found. Although the isolates in this
      collection were highly resistant to many antimicrobials, susceptibility to
      amikacin and meropenem was retained.

PMID- 24036891
TI  - Durability of lopinavir/ritonavir monotherapy in individuals with viral load <=50
      copies/ml in an observational setting.
AB  - BACKGROUND: The main objective is to evaluate the efficacy and durability of
      lopinavir-ritonavir monotherapy (LPV/r-MT) in virologically controlled HIV
      positive individuals switching from combination antiretroviral therapy (cART).
      METHODS: Criteria to be included in this observational study were to have
      initiated for the first time LPV/r-MT after >=2 consecutive HIV RNA<=50 copies/ml
      achieved on a >=3-drug-including regimen. The main end points were time to
      virological rebound (VR; defined in two ways: time of first of two consecutive
      viral load [VL]>50 and >200 copies/ml), time to discontinuation/intensification
      and time to experience either a single VL>200 copies/ml or
      discontinuation/intensification (treatment failure [TF]). Individuals' follow-up
      accrued from the date of starting LPV/r-MT to event or last available VL. Kaplan
      Meier curves and Cox regression analyses were used. RESULTS: A total of 228
      individuals were included: median age 46 years (IQR 40-50), 36% females, 36%
      intravenous drug users and 25% HCV-coinfected. Median CD4(+) T-cell count at
      nadir was 215 cell/mm(3) (IQR 116-336) and at baseline was 615 cell/mm(3) (IQR
      436-768). By 36 months after switching to LPV/r-MT, the proportion of individuals
      with VR (confirmed VL>200 copies/ml) was 11% and with TF was 35%. In the
      multivariable Cox model the factors associated with a lower risk of TF was the
      duration of viral suppression <50 copies/ml prior to baseline (ARH=0.92; 95% CI
      0.85, 0.99; P=0.024, per 6 months longer) and having LPV/r as part of last cART
      (ARH=0.45; 95% CI 0.21, 0.95; P=0.037). CONCLUSIONS: In daily clinical practice,
      we confirm a relatively safe approach of treatment simplification to LPV-MT in a
      selected population with long-lasting virological control.

PMID- 24036894
TI  - Basic presynaptic functions in hippocampal neurons are not affected by acute or
      chronic lithium treatment.
AB  - Lithium is an effective mood-stabilizer in the treatment of bipolar affective
      disorder. While glycogen synthase kinase 3-mediated and inositol depletion
      dependent effects of lithium have been described extensively in literature, there
      is very little knowledge about the consequences of lithium treatment on vesicle
      recycling and neurotransmitter availability. In the present study we have
      examined acute and chronic effects of lithium on synaptic vesicle recycling using
      primary hippocampal neurons. We found that exocytosis of readily releasable pool
      vesicles as well as recycling pool vesicles was unaffected by acute and chronic
      treatment within the therapeutic range or at higher lithium concentrations.
      Consistent with this observation, we also noticed that the network activity and
      number of active synapses within the network were also not significantly altered
      after lithium treatment. Taken together, as lithium treatment does not affect
      synaptic vesicle release at even high concentrations, our data suggest that
      therapeutic effects of lithium in bipolar affective disorder are not directly
      related to presynaptic function. 

PMID- 24036895
TI  - Low platelet iPLA2 activity predicts conversion from mild cognitive impairment to
      Alzheimer's disease: a 4-year follow-up study.
AB  - Reduced phospholipase A2 (PLA2) activity has been reported in the brain and in
      blood cells of patients with Alzheimer's disease (AD). Individuals with mild
      cognitive impairment (MCI) are at increased risk of developing AD. In the present
      study, we determined the activity of distinct PLA2 subgroups (iPLA2, sPLA2 and
      cPLA2) in older adults with MCI as compared to patients with mild dementia due to
      AD and to cognitively healthy controls. We investigated whether decreased PLA2
      activity at baseline is associated with the progression of MCI to AD upon follow
      up during a period of 4 years. The activity of PLA2 subgroups was determined in
      platelets from 169 elderly adults. Progression of MCI to AD was ascertained by
      standard clinical criteria for AD upon follow-up. At baseline, iPLA2 activity was
      significantly decreased (p = 0.001) in patients with AD and MCI as compared to
      controls. Patients with MCI who progressed to AD during follow-up showed
      significantly lower iPLA2 activity at baseline as compared to patients with MCI
      who did not progress to AD (p = 0.009). Moreover, subjects from the control group
      at baseline who progressed to MCI during follow-up had lower sPLA2 and cPLA2 (p =
      0.014 and p = 0.009, respectively). Our findings suggest that low platelet iPLA2
      activity may be a risk marker for AD in subjects with MCI. Moreover, low sPLA2
      and cPLA2 were related to cognitive decline in healthy controls, suggesting a
      relationship with the very early stages of the disease.

PMID- 24036896
TI  - Fluorescence turn-on response of a conjugated polyelectrolyte with intramolecular
      stack structure to biomacromolecules.
AB  - An anionic conjugated polyelectrolyte based on polydiphenylacetylene showed a
      significant fluorescence turn-on response to positively-charged proteins through
      a conformational relaxation of its intramolecular stack structure. 

PMID- 24036897
TI  - Atox1 contains positive residues that mediate membrane association and aid
      subsequent copper loading.
AB  - Copper chaperones bind intracellular copper and ensure proper trafficking to
      downstream targets via protein-protein interactions. In contrast to the
      mechanisms of copper binding and transfer to downstream targets, the mechanisms
      of initial copper loading of the chaperones are largely unknown. Here, we
      demonstrate that antioxidant protein 1 (Atox1 in human cells), the principal
      cellular copper chaperone responsible for delivery of copper to the secretory
      pathway, possesses the ability to interact with negatively charged lipid
      headgroups via distinct surface lysine residues. Moreover, loss of these residues
      lowers the efficiency of copper loading of Atox1 in vivo, suggesting that the
      membrane may play a scaffolding role in copper distribution to Atox1. These
      findings complement the recent discovery that the membrane also facilitates
      copper loading of the copper chaperone for superoxide dismutase 1 and provide
      further support for the emerging paradigm that the membrane bilayer plays a
      central role in cellular copper acquisition and distribution. 

PMID- 24036900
TI  - Ambulatory blood pressure monitoring, arterial function and other problems
      concerning hypertension.

PMID- 24036899
TI  - Inhibition of TGFbeta signaling promotes ground state pluripotency.
AB  - Embryonic stem (ES) cells are considered to exist in a ground state if shielded
      from differentiation triggers. Here we show that FGF4 and TGFbeta signaling
      pathway inhibitors, designated R2i, not only provide the ground state
      pluripotency in production and maintenance of naive ES cells from blastocysts of
      different mouse strains, but also maintain ES cells with higher genomic integrity
      following long-term cultivation compared with the chemical inhibition of the FGF4
      and GSK3 pathways, known as 2i. Global transcriptome analysis of the ES cells
      highlights augmented BMP4 signaling pathway. The crucial role of the BMP4 pathway
      in maintaining the R2i ground state pluripotency is demonstrated by BMP4 receptor
      suppression, resulting in differentiation and cell death. In conclusion, by
      inhibiting TGFbeta and FGF signaling pathways, we introduce a novel defined
      approach to efficiently establish the ground state pluripotency. 

PMID- 24036898
TI  - Overcoming chemoresistance of small-cell lung cancer through stepwise HER2
      targeted antibody-dependent cell-mediated cytotoxicity and VEGF-targeted
      antiangiogenesis.
AB  - Small-cell lung cancer (SCLC) easily recurs with a multidrug resistant phenotype.
      However, standard therapeutic strategies for relapsed SCLC remain unestablished.
      We found that human epidermal growth factor receptor 2 (HER2) is not only
      expressed in pretreated human SCLC specimens, but is also upregulated when HER2
      positive SCLC cells acquire chemoresistance. Trastuzumab induced differential
      levels of antibody-dependent cell-mediated cytotoxicity (ADCC) to HER2-positive
      SCLC cells. Furthermore, as a mechanism of the differential levels of ADCC, we
      have revealed that coexpression of intracellular adhesion molecule (ICAM)-1 on
      SCLC cells is essential to facilitate and accelerate the trastuzumab-mediated
      ADCC. Although SN-38-resistant SCLC cells lacking ICAM-1 expression were still
      refractory to trastuzumab, their in vivo growth was significantly suppressed by
      bevacizumab treatment due to dependence on their distinctive and abundant
      production of vascular endothelial growth factor. Collectively, stepwise
      treatment with trastuzumab and bevacizumab is promising for the treatment of
      chemoresistant SCLC. 

PMID- 24036901
TI  - The association between smoking quantity and hypertension mediated by
      inflammation in Chinese current smokers.
AB  - OBJECTIVES: Previous studies indicated that cigarette smokers were more likely to
      develop hypertension, and both smoking and hypertension were associated with
      inflammation. Whether inflammation mediates the relationship of them is unclear.
      This study aims to examine whether inflammation mediates the association between
      smoking and hypertension. METHODS: Nine hundred and eighty-four Chinese current
      smokers from a community-based chronic diseases survey in Guangzhou and Zhuhai
      were interviewed about sociodemographics, smoking, chronic conditions, and other
      health-related variables. Hypertension was defined according to 2007 European
      Society of Hypertension and European Society of Cardiology (ESH-ESC) Practice
      Guidelines. Inflammatory markers including C-reactive protein (CRP), interleukin
      (IL)-6, IL-1beta, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis
      factor-alpha (TNF-alpha), and vascular cell adhesion molecule-1 (VCAM-1) were
      measured by flow cytometry. Logistic regressions were performed to assess the
      mediation of inflammation on the relationship between smoking quantity and
      hypertension. RESULTS: We observed a positive association between smoking
      quantity and hypertension (P<0.05). After controlling for potential confounders,
      daily cigarette consumption was significantly associated with higher level of CRP
      and VCAM-1 and lower level of TNF-alpha among six measured inflammatory markers,
      and the current smokers with hypertension had significantly higher level of MCP-1
      and CRP than those smokers who were normotensive. Furthermore, the association
      between smoking quantity and hypertension was mediated by CRP, which accounted
      for 58.59% of the estimated causal effect of smoking on hypertension. CONCLUSION:
      We have confirmed previous observations that smoking quantity was positively
      associated with hypertension, and the results of our study suggested that the
      association between smoking and hypertension was probably mediated by CRP.

PMID- 24036902
TI  - Determination of central blood pressure by a noninvasive method (brachial blood
      pressure and QKD interval): a noninvasive validation.
AB  - OBJECTIVE: We validated against invasive measurements a measure of central SBP
      based on the QKD interval. The present objective is a comparison to the
      SphygmoCor device. MATERIALS AND METHODS: A first cohort was used to redefine an
      algorithm for estimating ascending aorta SBP (cSBP) with respect to SphygmoCor.
      This algorithm was then tested in a second cohort under static conditions and in
      a third cohort during a head-up tilt to study blood pressure variations. RESULTS:
      The first cohort (36 patients, mean age: 46 +/- 20 years, SBP: 114 +/- 19 mm Hg)
      defined the estimation algorithm as cSBP =62.687+1.35 * meanBP-0.207 * heart rate
      0.251 * height-0.1 * QKD (mean difference with SphygmoCor=0 +/- 7 mmHg).In the
      second cohort (105 patients, mean age: 51 +/- 19 years, SBP: 132 +/- 22 mmHg),
      the average difference between the two techniques was 2 +/- 6 mm Hg (R=0.93). The
      dynamic cohort included 31 patients (mean age: 49 +/- 23 years, SBP: 110 +/- 19
      mmHg) with 224 pairs of measurement. We studied the changes in central blood
      pressures compared with the basal state of each of the two techniques during head
      up tilt. With QKD, the average cSBP was 104 +/- 19 mmHg, the average variation
      was -13.00 mmHg +/- 15 (range 7-74 mmHg). With SphygmoCor, average cSBP was 10 
      mmHg +/- 18, the average variation was -14 mmHg   +/- 16 (range 2-81 mmHg). The
      variations in blood pressure with the two techniques were well correlated
      (R=0.93). CONCLUSION: cSBP estimation based on the QKD interval is comparable in
      precision to the SphygmoCor. Its ability to measure cSBP variations suggests that
      it could be employed for ambulatory measurements over 24 h.

PMID- 24036903
TI  - The Lin28/let-7a/c-Myc pathway plays a role in non-muscle invasive bladder
      cancer.
AB  - We investigate the role of the Lin28/let-7a/c-Myc pathway in non-muscle invasive
      bladder cancer (NMIBC). Using RT-PCR, western blot and immunohistochemistry
      techniques, the levels of pre-let-7a, let-7a, Lin28 and c-Myc RNA and/or proteins
      were determined in samples of normal bladder tissue and bladder cancer.
      Expression of pre-let-7a was found to be negatively correlated with the
      pathological grade of bladder cancer, while let-7a showed a positive correlation
      with bladder cancer pathological grade. Expression of Lin28 RNA and protein was
      not significantly different between normal bladder tissue and low-grade
      transitional cell carcinoma of bladder (TCC) but the expression levels in high
      grade TCC were remarkably increased. Expression of c-Myc RNA and protein was
      significantly higher in bladder cancer samples in comparison to normal bladder
      tissue without correlation with cancer differentiation. Expression of all the
      above RNAs and proteins showed no significant difference in Ta and T1 stages. The
      Lin28/let-7a/c-Myc pathway plays an important role in NMIBC. In particular,
      expression levels of let-7a correlate with the degree of cancer differentiation
      but not cancer stage. 

PMID- 24036904
TI  - [Imaging following valve replacement].
AB  - Patients who undergo heart valve replacement require lifelong cardiac follow-up
      care. Although the primary pathology of the patient is treated by valve
      replacement, the risk of postoperative complications and structural failure of
      the implanted device requires regular check-ups where imaging plays an important
      role. Immediately after surgery reference values regarding prosthetic and cardiac
      function for further check-ups are obtained. Transthoracic and transesophageal
      echocardiography are the imaging modalities of choice for standard examination
      and follow-up due to their availability and low costs. However, when it comes to
      identification of complications they are often insufficient. Magnetic resonance
      imaging (MRI) and computed tomography (CT) play an increasingly important role as
      complementary modalities for the detection and monitoring of complications after
      valve replacement. The following article gives an overview of the current non
      invasive examination methods and the use in the investigation of postoperative
      complications.

PMID- 24036905
TI  - [Minimally invasive pulmonary valve replacement in pediatric patients: importance
      of imaging].
AB  - CLINICAL/METHODICAL ISSUE: Right ventricular outflow tract (RVOT) dysfunction
      with pulmonary regurgitation or obstruction is a common postsurgical consequence
      in congenital heart disease. STANDARD RADIOLOGICAL METHODS: Magnetic resonance
      imaging (MRI) is widely accepted as standard method of imaging in congenital
      heart disease. It provides anatomical and functional information without
      radiation exposure and is therefore well suited for serial examinations.
      METHODICAL INNOVATIONS: Percutaneous pulmonary valve implantation (PPVI) has been
      shown to be a safe and effective treatment option for patients with pulmonary
      valve insufficiency or stenosis. Correct patient selection for PPVI is crucial.
      It is important to be familiar with the indications and anatomical requirements
      for stent placement and to tailor imaging protocols. PERFORMANCE: Imaging the
      RVOT, assessment of right ventricular volumes and function and calculation of
      pulmonary flow and regurgitation are core elements of the MRI examination prior
      to PPVI. Low interobserver and intraobserver variation allows even small changes
      to be detected. ACHIEVEMENTS: Imaging provides relevant information for correct
      patient selection for PPVI and is part of postinterventional follow-up. Imaging
      is an important tool for documentation of success and for detection of
      complications. PRACTICAL RECOMMENDATIONS: Several imaging modalities are used for
      evaluation of RVOTs; however, MRI can provide answers to most questions without
      radiation exposure.

PMID- 24036906
TI  - Kaposi's varicelliform eruption.

PMID- 24036907
TI  - Serum epidermal growth factor is associated with prognosis and hormone receptor
      status in patients with HER2-positive metastatic breast cancer treated with first
      line trastuzumab plus taxane chemotherapy.
AB  - PURPOSE: Epidermal growth factor (EGF) is a ligand for the epidermal growth
      factor receptor (EGFR). Human epidermal growth factor receptor 2 (HER2) shares
      common signal pathways and forms a heterodimer with EGFR. In this study, we
      investigated the clinical and pathologic implications of serum EGF levels in
      patients with HER2-positive metastatic breast cancer (MBC). METHODS: We analyzed
      serum EGF levels from baseline serum samples of consecutive patients with HER2
      positive MBC who received first-line trastuzumab plus taxane chemotherapy and
      correlated them with treatment outcomes and pathologic features. RESULTS: A total
      of 50 women were analyzed. The median age was 47 years (range 27-72 years).
      Patients with high serum EGF levels (>=10.0 pg/mL) had significantly longer
      overall survival (47.0 months (95 % confidence interval (CI) 28.3-65.7 months)
      vs. 23.3 months (95 % CI 13.5-33.1 months); p = 0.009) with a tendency toward
      longer progression-free survival (p = 0.123). Serum EGF levels were not
      associated with hematologic or cardiac adverse events. Progesterone receptor
      positive patients had significantly higher serum EGF levels than progesterone
      receptor-negative patients (24.3 pg/mL (range 9.5-69.0 pg/mL) vs. 12.3 pg/mL
      (range 0.0-59.5 pg/mL); p = 0.006). CONCLUSIONS: Our data suggest that high serum
      EGF levels may be associated with good prognosis in patients with HER2-positive
      MBC receiving trastuzumab plus taxane chemotherapy. In addition, serum EGF levels
      were associated with progesterone receptor positivity.

PMID- 24036908
TI  - Population pharmacokinetics of dimethylacetamide in children during standard and
      once-daily IV busulfan administration.
AB  - PURPOSE: N,N-dimethylacetamide (DMA) is administered to children during high-dose
      chemotherapy as a solubilizer with the intravenous formulation of busulfan
      (Busilvex(r)). DMA has shown liver toxicity in rats. However, little is known
      regarding its pharmacokinetics (PK) in humans. The aim of this analysis was to
      compare the PK of DMA after a once-daily dose of Busilvex(r) with the standard
      scheme consisting of 3-4 administrations per day in children. METHODS: Out of 42
      children, aged 0.1-18.9 years, receiving Busilvex(r), 18 children received the
      first dose as a loading dose, giving a double dose of 1.4-2.0 mg/kg over a 4 h
      infusion followed by 15 doses of 0.7-1.0 mg/kg as 2 h infusions every 6 h. The
      other 24 children received Busilvex(r) as 3 h infusions once-daily for 4
      consecutive days with a targeted busulfan AUC of 4,263 MUM*min. Using NONMEMTM
      plasma, concentration-time data were analyzed. Assuming an increase in clearance
      overtime as found in our previous investigation, separate time factors for the
      two different dosing schedules included in the dataset were tested. RESULTS: A
      one-compartment model with clearance increasing over time described the DMA
      kinetics sufficiently. Peak plasma concentrations of DMA, up to 3.09 mmoL/L
      (median 0.75 mmoL/L) for the current licensed dose regimen and up to 8.77 mmoL/L
      (median 3 mmoL/L) for the once-daily application, were observed. The examined
      increase in clearance was found to be 58 mL/h/kg and 6.1 mL/h/kg per day for the
      current licensed and the once-daily dose regimen, respectively. CONCLUSION: N,N
      dimethylacetamide as solvent of lipophilic drugs such as busulfan has a linear PK
      in children of all ages using a dose split into one or four administrations per
      day. The rapid clearance with different dosing in patients of different body
      weights indicates that it is safe to use DMA in children in both a once and four
      times daily regimen.

PMID- 24036909
TI  - Comparison of the MpEF1alpha and CaMV35 promoters for application in Marchantia
      polymorpha overexpression studies.
AB  - Constitutive promoters are essential tools for analyses of gene functions by
      transgenic approaches. For overexpression and silencing studies of genes, a
      ubiquitous and strong expression of genes under investigation as well as
      selection markers is preferred. For future applications in the emerging basal
      plant model system Marchantia polymorpha, a liverwort, activities of the viral
      35S cauliflower mosaic virus promoter and the endogenous elongation factor 1alpha
      (MpEF1alpha) promoter were analyzed. Expression of the reporter gene beta
      glucuronidase (GUS), driven by the CaMV35 and MpEF1alpha promoters, was compared
      throughout plant development. Significant differences were observed between the
      two promoter activities. The CaMV35 promoter yields a weak reporter gene
      expression in the meristematic zones but drives a strong expression in the
      thallus. The MpEF1alpha promoter causes a strong meristematic GUS expression and
      is more active in female sexual tissues. Overall, the MpEF1alpha promoter seems
      to be the better option for obtaining a strong and ubiquitous transgene
      expression. Furthermore, a whole mount in situ hybridization protocol for
      Marchantia was established. Analysis of MpEF1alpha mRNA transcript in intact,
      whole tissues showed an expression pattern that is overall similar to the pattern
      of the GUS reporter gene expression driven by the MpEF1alpha promoter, including
      strong expression in meristematic zones. The whole mount technique reported here
      can be used to determine the mRNA expression in intact gemmae and archegonia, and
      has the potential to be applied for screening large numbers of transgenic plants,
      for instance to identify knock-down mutants. 

PMID- 24036910
TI  - Involvement of Src tyrosine kinase and protein kinase C in the expression of
      macrophage migration inhibitory factor induced by H2O2 in HL-1 mouse cardiac
      muscle cells.
AB  - Macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, plays an
      important role in the pathogenesis of atrial fibrillation; however, the upstream
      regulation of MIF in atrial myocytes remains unclear. In the present study, we
      investigated whether and how MIF is regulated in response to the renin
      angiotensin system and oxidative stress in atrium myocytes (HL-1 cells). MIF
      protein and mRNA levels in HL-1 cells were assayed using immunofluorescence, real
      time PCR, and Western blot. The result indicated that MIF was expressed in the
      cytoplasm of HL-1 cells. Hydrogen peroxide (H2O2), but not angiotensin II,
      stimulated MIF expression in HL-1 cells. H2O2-induced MIF protein and gene levels
      increased in a dose-dependent manner and were completely abolished in the
      presence of catalase. H2O2-induced MIF production was completely inhibited by
      tyrosine kinase inhibitors genistein and PP1, as well as by protein kinase C
      (PKC) inhibitor GF109203X, suggesting that redox-sensitive MIF production is
      mediated through tyrosine kinase and PKC-dependent mechanisms in HL-1 cells.
      These results suggest that MIF is upregulated by HL-1 cells in response to redox
      stress, probably by the activation of Src and PKC. 

PMID- 24036911
TI  - Myocardial remodeling and bioelectric changes in tachycardia-induced heart
      failure in dogs.
AB  - In this study, electrical and structural remodeling of ventricles was examined in
      tachycardia-induced heart failure (HF). We studied two groups of weight-matched
      adult male mongrel dogs: a sham-operated control group (n=5) and a pacing group
      (n=5) that underwent ventricular pacing at 230 bpm for 3 weeks. Clinical symptoms
      of congestive HF were observed in both groups. Their hemodynamic parameters were
      determined and the severity of the HF was evaluated by M-mode echocardiography.
      Changes in heart morphology were observed by scanning electron and light
      microscopy. Ventricular action potential duration (APD), as well as the 50 and
      90% APD were measured in both groups. All dogs exhibited clinical symptoms of
      congestive HF after rapid right ventricular pacing for 3 weeks. These data
      indicate that rapid, right ventricular pacing produces a useful experimental
      model of low-output HF in dogs, characterized by biventricular pump dysfunction,
      biventricular cardiac dilation, and non-ischemic impairment of left ventricular
      contractility. Electrical and structural myocardial remodeling play an essential
      role in congestive HF progression, and should thus be prevented.

PMID- 24036912
TI  - Diastolic function is associated with quality of life and exercise capacity in
      stable heart failure patients with reduced ejection fraction.
AB  - Exercise capacity and quality of life (QOL) are important outcome predictors in
      patients with systolic heart failure (HF), independent of left ventricular (LV)
      ejection fraction (LVEF). LV diastolic function has been shown to be a better
      predictor of aerobic exercise capacity in patients with systolic dysfunction and
      a New York Heart Association (NYHA) classification >= II. We hypothesized that
      the currently used index of diastolic function E/e' is associated with exercise
      capacity and QOL, even in optimally treated HF patients with reduced LVEF. This
      prospective study included 44 consecutive patients aged 55 +/- 11 years (27 men
      and 17 women), with LVEF<0.50 and NYHA functional class I-III, receiving optimal
      pharmacological treatment and in a stable clinical condition, as shown by the
      absence of dyspnea exacerbation for at least 3 months. All patients had
      conventional transthoracic echocardiography and answered the Minnesota Living
      with HF Questionnaire, followed by the 6-min walk test (6MWT). In a multivariable
      model with 6MWT as the dependent variable, age and E/e' explained 27% of the
      walked distance in 6MWT (P=0.002; multivariate regression analysis). No
      association was found between walk distance and LVEF or mitral annulus systolic
      velocity. Only normalized left atrium volume, a sensitive index of diastolic
      function, was associated with decreased QOL. Despite the small number of patients
      included, this study offers evidence that diastolic function is associated with
      physical capacity and QOL and should be considered along with ejection fraction
      in patients with compensated systolic HF.

PMID- 24036913
TI  - Interaction of FUS and HDAC1 regulates DNA damage response and repair in neurons.
AB  - Defects in DNA repair have been extensively linked to neurodegenerative diseases,
      but the exact mechanisms remain poorly understood. We found that FUS, an RNA/DNA
      binding protein that has been linked to amyotrophic lateral sclerosis (ALS) and
      frontotemporal lobar degeneration, is important for the DNA damage response
      (DDR). The function of FUS in DDR involved a direct interaction with histone
      deacetylase 1 (HDAC1), and the recruitment of FUS to double-stranded break sites
      was important for proper DDR signaling. Notably, FUS proteins carrying familial
      ALS mutations were defective in DDR and DNA repair and showed a diminished
      interaction with HDAC1. Moreover, we observed increased DNA damage in human ALS
      patients harboring FUS mutations. Our findings suggest that an impaired DDR and
      DNA repair may contribute to the pathogenesis of neurodegenerative diseases
      linked to FUS mutations. 

PMID- 24036914
TI  - Synapse maturation by activity-dependent ectodomain shedding of SIRPalpha.
AB  - Formation of appropriate synaptic connections is critical for proper functioning
      of the brain. After initial synaptic differentiation, active synapses are
      stabilized by neural activity-dependent signals to establish functional synaptic
      connections. However, the molecular mechanisms underlying activity-dependent
      synapse maturation remain to be elucidated. Here we show that activity-dependent
      ectodomain shedding of signal regulatory protein-alpha (SIRPalpha) mediates
      presynaptic maturation. Two target-derived molecules, fibroblast growth factor 22
      and SIRPalpha, sequentially organize the glutamatergic presynaptic terminals
      during the initial synaptic differentiation and synapse maturation stages,
      respectively, in the mouse hippocampus. SIRPalpha drives presynaptic maturation
      in an activity-dependent fashion. Remarkably, neural activity cleaves the
      extracellular domain of SIRPalpha, and the shed ectodomain in turn promotes the
      maturation of the presynaptic terminal. This process involves calcium/calmodulin
      dependent protein kinase, matrix metalloproteinases and the presynaptic receptor
      CD47. Finally, SIRPalpha-dependent synapse maturation has an impact on synaptic
      function and plasticity. Thus, ectodomain shedding of SIRPalpha is an activity
      dependent trans-synaptic mechanism for the maturation of functional synapses. 

PMID- 24036915
TI  - An illusion predicted by V1 population activity implicates cortical topography in
      shape perception.
AB  - Mammalian primary visual cortex (V1) is topographically organized such that the
      pattern of neural activation in V1 reflects the location and spatial extent of
      visual elements in the retinal image, but it is unclear whether this organization
      contributes to visual perception. We combined computational modeling, voltage
      sensitive dye imaging (VSDI) in behaving monkeys and behavioral measurements in
      humans to investigate whether the large-scale topography of V1 population
      responses influences shape judgments. Specifically, we used a computational model
      to design visual stimuli that had the same physical shape, but were predicted to
      elicit variable V1 response spread. We confirmed these predictions with VSDI.
      Finally, we designed a behavioral task in which human observers judged the shapes
      of these stimuli and found that their judgments were systematically distorted by
      the spread of V1 activity. This illusion suggests that the topographic pattern of
      neural population responses in visual cortex contributes to visual perception. 

PMID- 24036916
TI  - Influence of vanadium doping on the electrochemical performance of nickel oxide
      in supercapacitors.
AB  - In this study, V-doped NiO materials were prepared by simple coprecipitation and
      thermal decomposition, and the effect of the vanadium content on the morphology,
      structural properties, electrochemical behavior, and cycling stability of NiO
      upon oxidation and reduction was analyzed for supercapacitor applications. The
      results show an improvement in the capacitive characteristics of the V-doped NiO,
      including increases in the specific capacitance after the addition of just 1.0,
      2.0, and 4.0 at% V. All VxNi1-xO electrodes (x = 0.01, 0.02, 0.04) exhibited
      higher specific capacitances of 371.2, 365.7, and 386.2 F g(-1) than that of pure
      NiO (303.2 F g(-1)) at a current density of 2 A g(-1) after 500 cycles,
      respectively. The V0.01Ni0.99O electrode showed good capacitance retention of
      73.5% at a current density of 2 A g(-1) for more than 500 cycles in a cycling
      test. Importantly, the rate capability of the V0.01Ni0.99O electrode was
      maintained at about 84.7% as discharge current density was increased from 0.5 A
      g(-1) to 4 A g(-1).

PMID- 24036918
TI  - Clinical features and treatment strategies for older prostate cancer patients
      with bone metastasis.
AB  - To identify the clinical features and independent predictors of survival in older
      patients with bone metastasis from prostate cancer (PCa). We retrospectively
      analysed 205 older patients with bone metastases from PCa between 1997 and 2012.
      The Kaplan-Meier method was used with the log-rank test for survival rate
      calculations and to evaluate each variable. Multivariate analysis was performed
      with the Cox regression model. The chi-squared test was used to compare survival
      rates between older and younger (n=197) patients. All patients were followed up.
      The 1-, 2-, 3- and 5-year survival rates were 95.5%, 77.5%, 68.5% and 33.7%,
      respectively. Gleason score, radiotherapy of the primary tumour, the number of
      bone metastases, the alkaline phosphatase alkaline phosphatase (ALP) level, organ
      metastasis and regional lymph node metastasis were associated with the survival
      rates. Multivariate Cox regression analysis showed that Gleason score at
      diagnosis of the primary tumour was a significant predictor of overall survival
      following the diagnosis of bone metastases. In addition, the overall survival
      rates of older patients were higher compared with younger patients, but older
      patients who underwent radiotherapy had higher mortality. These data may serve as
      a guide for creating clinical prediction models in further studies.

PMID- 24036919
TI  - Penile metastasis of osteosarcoma: a rare case report.

PMID- 24036917
TI  - Non-coding Y RNAs as tethers and gates: Insights from bacteria.
AB  - Non-coding RNAs (ncRNAs) called Y RNAs are abundant components of both animal
      cells and a variety of bacteria. In all species examined, these ~100 nt RNAs are
      bound to the Ro 60 kDa (Ro60) autoantigen, a ring-shaped protein that also binds
      misfolded ncRNAs in some vertebrate nuclei. Although the function of Ro60 RNPs
      has been mysterious, we recently reported that a bacterial Y RNA tethers Ro60 to
      the 3' to 5' exoribonuclease polynucleotide phosphorylase (PNPase) to form RYPER
      (Ro60/Y RNA/PNPase Exoribonuclease RNP), a new RNA degradation machine. PNPase is
      a homotrimeric ring that degrades single-stranded RNA, and Y RNA-mediated
      tethering of Ro60 increases the effectiveness of PNPase in degrading structured
      RNAs. Single particle electron microscopy of RYPER suggests that RNA threads
      through the Ro60 ring into the PNPase cavity. Further studies indicate that Y
      RNAs may also act as gates to regulate entry of RNA substrates into the Ro60
      channel. These findings reveal novel functions for Y RNAs and raise questions
      about how the bacterial findings relate to the roles of these ncRNAs in animal
      cells. Here we review the literature on Y RNAs, highlighting their close
      relationship with Ro60 proteins and the hypothesis that these ncRNAs function
      generally to tether Ro60 rings to diverse RNA-binding proteins. 

PMID- 24036920
TI  - Influence of obesity on localized prostate cancer patients treated with radical
      prostatectomy.
AB  - This study aimed to investigate the association between different anthropometric
      measures of obesity and clinicopathological characteristics in Chinese patients
      with clinically localized prostate cancer (PCa). A total of 734 patients with
      clinically localized PCa who underwent radical prostatectomy (RP) were included
      in this study. Clinical and pathological data from each patient were collected.
      Anthropometric measures of abdominal adiposity were measured from T2-weighted
      sagittal localisation images from magnetic resonance imaging (MRI) for 413
      (56.3%) patients. Patient clinical and pathological characteristics were compared
      across body mass index (BMI) groups. Univariable and multivariable logistic
      regression models were used to address the influence of the preoperative total
      testosterone level and anthropometric measures of obesity on pathological
      outcomes. In the multivariate analysis, BMI was not significantly associated with
      any pathological outcomes. However, the percentage of visceral adipose tissue
      (VAT%) was an independent predictor of a pathological Gleason score >=8
      (P<0.001), extracapsular extension (ECE; P=0.002) and seminal vesicle invasion
      (SVI; P=0.007). More importantly, we found that the preoperative total
      testosterone level was significantly correlated with the VAT% (Pearson's
      correlation coefficient: -0.485, P<0.001) and subcutaneous adipose tissue (SAT;
      Pearson's correlation coefficient: 0.413, P<0.001). In conclusion, the results of
      this study suggest that abdominal fat distribution, and particularly VAT%, is
      associated with a risk of advanced PCa. Moreover, our present study confirms a
      significant inverse correlation between visceral adiposity and testosterone.
      Further studies are warranted to elucidate the biological mechanisms underlying
      the relationship between abdominal adiposity and the aggressiveness of PCa.

PMID- 24036921
TI  - Bubble template synthesis of Sn2Nb2O7 hollow spheres for enhanced visible-light
      driven photocatalytic hydrogen production.
AB  - Hierarchical Sn2Nb2O7 hollow spheres were prepared for the first time via a
      facile hydrothermal route using bubbles generated in situ from the decomposition
      of urea as soft templates. The as-obtained hollow spheres with a large specific
      surface area of 58.3 m(2) g(-1) show improved visible-light-driven photocatalytic
      H2 production activity in lactic acid aqueous solutions, about 4 times higher
      than that of the bulk Sn2Nb2O7 sample prepared by a conventional high temperature
      solid state reaction method. 

PMID- 24036922
TI  - Discrepancies between Doppler and catheter gradients in ventricular septal
      defect: a correction of localized gradients from pressure recovery phenomenon.
AB  - Although very high gradient levels were measured during the evaluation of
      ventricular septal defect (VSD) in daily practice, these measurements are
      generally interpreted as erroneous and thus neglected. Our aim was to assess the
      features of VSD's having erroneous interventricular pressure gradients by
      echocardiography. A 46 patients were enrolled in the study. The patients with
      higher Doppler-derived interventricular gradient than brachial systolic blood
      pressure were compared with patients with lower gradient (group 1, n = 26; group
      2, n = 20, respectively) in terms of echocardiographic characteristics of VSD. No
      significant relations were observed in systolic and diastolic blood pressure and
      interventricular synchronicity between two groups (117.1 +/- 6.7 vs 110.2 +/- 6.3
      mmHg, p = 0.145; 74.7 +/- 4.3 vs 73.2 +/- 4.9 mmHg, p = 0.32; 31.2 +/- 5.5 vs
      33.2 +/- 4.9 msn, p = 0.29, respectively). Left ventricular end-diastolic and end
      systolic diameters were greater in group 2 (46.6 +/- 3.5 vs 49.5 +/- 4.5, p =
      0.022; 30.3 +/- 2.5 vs 32.9 +/- 3.2, p = 0.004, respectively). Doppler-derived
      interventricular pressure gradients were significantly higher in group 1 (144.4
      +/- 13.6 vs 75.7 +/- 5.1 mmHg, p < 0.001, respectively). Defect width was
      significantly lower (3.20 +/- 0.40 vs 4.8 +/- 1.8 mm, respectively, p < 0.05),
      and length was greater in group 1 patients (5.75 +/- 0.90 vs 2.80 +/- 0.80 mm, p
      < 0.05, respectively). There was a significant positive correlation between
      pressure gradient and defect length (r = 0.84, p < 0.001), and a negative
      correlation between pressure gradient and defect width (r = -0.66, p < 0.001).
      Defect length/width was significantly greater in group 1. With the cut-off value
      of 1.2, defect length/width was able to predict tunnel-type VSD with sensitivity
      of 88.5% and specificity of 72.7%. Continuous-wave Doppler method may
      overestimate interventricular pressure gradients in patients with tunnel-type
      ventricular septal defect.

PMID- 24036923
TI  - Quantitative assessment of joint position sense recovery in subacute stroke
      patients: a pilot study.
AB  - OBJECTIVE: To assess joint position sense performance in subacute stroke patients
      using a novel quantitative assessment. DESIGN: Proof-of-principle pilot study
      with a group of subacute stroke patients. Assessment at baseline and after 2
      weeks of intervention. Additional data for a healthy age-matched control group.
      SUBJECTS/PATIENTS: Ten subacute stroke patients (aged 65.41 years (standard
      deviation 2.5), 4 females, 2.3 weeks (standard deviation 0.2)) post-stroke
      receiving in-patient standard rehabilitation and repetitive electrical
      stimulation of the affected hand. METHODS: Joint position sense was assessed
      based on the ability of correctly perceiving the opening angles of the finger
      joints. Patients had to report size differences of polystyrene balls of various
      sizes, whilst the balls were enclosed simultaneously by the affected and the non
      affected hands. A total of 21 pairwise size comparisons was used to quantify
      joint position performance. RESULTS: After 2 weeks of therapeutic intervention a
      significant improvement in joint position sense performance was observed;
      however, the performance level was still below that of a healthy control group.
      CONCLUSIONS: The results indicate high feasibility and sensitivity of the joint
      position test in subacute stroke patients. Testing allowed quantification of both
      the deficit and the rehabilitation outcome.

PMID- 24036924
TI  - Intravenous tenecteplase in acute ischemic stroke: an updated review.
AB  - Tenecteplase in a genetically engineered variant of alteplase. Although the two
      have the same mechanism of action, tenecteplase has properties that makes it a
      seemingly more advantageous thrombolytic. Because of its rapid single-bolus
      administration, its use is favored over alteplase in the treatment of acute
      myocardial infarction. Over the past few years, several clinical studies have
      been conducted to assess the safety, feasibility, and efficacy of tenecteplase in
      ischemic stroke. In spite of the mixed results of these studies, experimentation
      with tenecteplase continues in from of clinical trials. In this article, the
      utility of tenecteplase in ischemic stroke will be discussed. 

PMID- 24036925
TI  - Pediatric norovirus infection.
AB  - Noroviruses (NoVs) are among the most frequent causes of acute pediatric
      gastroenteritis. Although the disease is often self-limiting and recovery is the
      rule, it constitutes an important health problem because of its highly contagious
      nature and the high rate of morbidity. NoVs are responsible for 47-96 % of
      outbreaks of acute pediatric gastroenteritis, and 5-36 % of sporadic cases. NoV
      induced gastroenteritis is a frequent cause of hospitalization, and severe and
      sometimes fatal cases have been reported in immunocompromised children. The
      increasing recognition of NoVs as the cause of pediatric disease and the limited
      success in preventing outbreaks have led to consideration of vaccines. However,
      while awaiting the development of a vaccine, there is an urgent need for more
      epidemiological data concerning childhood NoV infection, including the impact of
      NoVs on different age groups, the possible etiological role of NoVs in infections
      other than gastroenteritis, and the socioeconomic impact of NoVs on households.

PMID- 24036926
TI  - Absolute quantification of choline-related biomarkers in breast cancer biopsies
      by liquid chromatography electrospray ionization mass spectrometry.
AB  - It has been repeatedly demonstrated that choline metabolism is altered in a wide
      variety of cancers. In breast tumours, the choline metabolite profile is
      characterized by an elevation of phosphocholine and total choline-compounds. This
      pattern is increasingly being exploited as biomarker in cancer diagnosis. The
      majority of in vitro metabolomics studies, for biomarkers quantification in cell
      cultures or tissues, entail proton NMR spectroscopy. Although many "targeted"
      approaches have been proposed to quantify metabolites from standard one
      dimensional (1D) NMR experiments, the task is often made difficult by the high
      degree of overlap characterizing 1H NMR spectra of biological samples. Here we
      present an optimized protocol for tissue extraction and absolute quantification
      of choline, phosphocholine and glycerophosphocholine by means of liquid
      chromatography electrospray ionization mass spectrometry (LC-ESI-MS). The
      selected chromatographic separation system with a HILIC (hydrophilic interaction
      chromatography) amide column effectively separates free choline and its
      phopshorylated derivatives, contrary to failure observed using standard reversed
      phase chromatography. The metabolite absolute quantification is based on external
      calibration with commercial standards, and is validated by a parallel 1D proton
      NMR analysis. The LC-MS/NMR analysis is applied to three breast carcinoma
      specimens obtained by surgical excision, each one accompanied by a control tissue
      sample taken outside the tumor margin. The metabolite concentrations measured are
      in good agreement with previous results on metabolic profile changes of breast
      cancer. Each of the three cancerous biopsies, when compared with the control
      tissue, exhibit a highly increased levels phosphocholine, total choline and
      phosphocholine/glycerophosphocholine ratio. 

PMID- 24036927
TI  - The human foramen magnum--normal anatomy of the cisterna magna in adults.
AB  - INTRODUCTION: The goal of this study was to radiologically describe the
      anatomical characteristics of the cisterna magna (CM) with regard to presence,
      dimension, and configuration. METHODS: In this retrospective study, 523 records
      were reviewed. We defined five CM types, the range of which covered all normal
      variants found in the study population. Characteristics of the CM were recorded
      and correlations between various posterior fossa dimensions and CM volume
      determined. RESULTS: There were 268 female (mean age 50.9 +/- 16.9 years) and 255
      male (mean age 54.1 +/- 15.8 years) patients. CM volume was smaller in females
      than in males and correlated with age (Pearson correlation, r = 0.1494, p =
      0.0006) and gender (unpaired t test, r (2) = 0.0608, p < 0.0001). Clivus length
      correlated with CM volume (Pearson correlation, r = 0.211, p < 0.0001) and gender
      (unpaired t test, r (2) = 0.2428, p < 0.0001). Tentorial angle did not correlate
      with CM volume (Pearson correlation, r = -0.0609, p < 0.1642) but did correlate
      with gender (unpaired t test, r (2) = 0.0163, p < 0.0035). The anterior-posterior
      dimension of cerebrospinal fluid anterior to the brainstem correlated with CM
      volume (Pearson correlation, r = 0.181, p < 0.0001) and gender (unpaired t test,
      r (2) = 0.0205, p = 0.001). CONCLUSION: The anatomical description and simple
      classification system we define allows for a more precise description of
      posterior fossa anatomy and could potentially contribute to the understanding of
      Chiari malformation anatomy and management.

PMID- 24036929
TI  - High-mobility graphene on liquid p-block elements by ultra-low-loss CVD growth.
AB  - The high-quality and low-cost of the graphene preparation method decide whether
      graphene is put into the applications finally. Enormous efforts have been devoted
      to understand and optimize the CVD process of graphene over various d-block
      transition metals (e.g. Cu, Ni and Pt). Here we report the growth of uniform high
      quality single-layer, single-crystalline graphene flakes and their continuous
      films over p-block elements (e.g. Ga) liquid films using ambient-pressure
      chemical vapor deposition. The graphene shows high crystalline quality with
      electron mobility reaching levels as high as 7400 cm(2) V(-1) s(-1) under ambient
      conditions. Our employed growth strategy is ultra-low-loss. Only trace amounts of
      Ga are consumed in the production and transfer of the graphene and expensive film
      deposition or vacuum systems are not needed. We believe that our research will
      open up new territory in the field of graphene growth and thus promote its
      practical application.

PMID- 24036928
TI  - Integrin-beta5 and zyxin mediate formation of ventral stress fibers in response
      to transforming growth factor beta.
AB  - Cell adhesion to the extracellular matrix is an essential element of various
      biological processes. TGF-beta cytokines regulate the matrix components and cell
      matrix adhesions. The present study investigates the molecular organization of
      TGF-beta-induced matrix adhesions. The study demonstrates that in various mouse
      and human epithelial cells TGF-beta induces cellular structures containing 2
      matrix adhesions bridged by a stretch of actin fibers. These structures are
      similar to ventral stress fibers (VSFs). Suppression of integrin-beta5 by RNA
      interference reduces VSFs in majority of cells (> 75%), while overexpression of
      integrin-beta5 fragments revealed a critical role of a distinct sequence in the
      cytoplasmic domain of integrin-beta5 in the VSF structures. In addition, the
      integrity of actin fibers and Src kinase activity contribute to integrin-beta5
      mediated signaling and VSF formation. TGF-beta-Smad signaling upregulates actin
      regulatory proteins, such as caldesmon, zyxin, and zyxin-binding protein Csrp1 in
      mouse and human epithelial cells. Suppression of zyxin markedly inhibits
      formation of VSFs in response to TGF-beta and integrin-beta5. Zyxin is localized
      at actin fibers and matrix adhesions of VSFs and might bridge integrin-beta5
      mediated adhesions to actin fibers. These findings provide a platform for
      defining the molecular mechanism regulating the organization and activities of
      VSFs in response to TGF-beta. 

PMID- 24036930
TI  - Biocontrol attack increases pollen limitation under some circumstances in the
      invasive plant Centaurea solstitialis.
AB  - Herbivore damage often deters pollinator visitation and many invasive plants in
      North America are pollinator-dependent. This has important implications for the
      biological control of invasive plants because it means that agents that deter
      pollinators may have a larger than expected impact on the plant. Yet interactions
      between pollinators and biocontrol agents are rarely evaluated. Centaurea
      solstitialis, one of the most problematic invasive species in California, is
      dependent on pollinators for reproduction. I factorially manipulated infection by
      a biocontrol pathogen and pollen supplementation to test for (1) pollen
      limitation in C. solstitialis, (2) whether infection increased pollen limitation,
      and (3) whether this varied across a soil moisture gradient. Plants growing on
      north-facing slopes where soil moisture was higher experienced mild pollen
      limitation in the absence of the pathogen and more pronounced pollen limitation
      when they were infected. Plants on drier south-facing slopes did not suffer from
      pollen limitation but instead appeared to suffer from resource limitation.
      Pathogen infection directly reduced seed set in C. solstitialis by 67-72%. On
      north-facing slopes, infection had an additional, indirect effect by increasing
      the degree of pollen limitation plants experienced. The trait that mediates this
      indirect pathogen-pollinator interaction is the number of inflorescences plants
      produced: infected plants made fewer inflorescences which led to greater pollen
      limitation. Although in the present study this outcome is dependent on abiotic
      factors that vary over small spatial scales, exploiting other invasive plants'
      dependence on pollinators by selecting agents that deter visitation may enhance
      agent impact.

PMID- 24036931
TI  - Varying impacts of cervid, hare and vole browsing on growth and survival of
      boreal tree seedlings.
AB  - The negative impacts of mammalian herbivores on plants have been studied quite
      extensively, but typically with only a single herbivore species at a time. We
      conducted a novel comparison of the browsing effects of voles, hares and cervids
      upon the growth and survival of boreal tree seedlings. This was done by excluding
      varying assemblages of these key mammalian herbivores from silver birch, Scots
      pine and Norway spruce seedlings for 3 years. We hypothesised that the pooled
      impacts of the herbivores would be greater than that of any individual group,
      while the cervids would be the group with the strongest impact. Growth of birch
      seedlings advanced when cervids were excluded whereas growth of seedlings
      accessible to cervids was hindered. Survival of all seedlings was lowest when
      they were accessible to voles and voles plus hares, whereas cervids seemed not to
      influence seedling survival. Our results show that the impact of herbivores upon
      woody plants can be potent in the boreal forests, but the mechanism and strength
      of this link depends on the tree and herbivore species in question. Risk of
      abated stand regeneration appears highest for the deciduous birch, though there
      is need for seedling protection also in coniferous stands. The clear cervid
      mediated growth limitation of birch also indicates potential for a trophic
      cascade effect by mammalian top predators, currently returning to boreal
      ecosystems.

PMID- 24036932
TI  - Difference in defense strategy in flower heads and leaves of Asteraceae: multiple
      species approach.
AB  - Although a vast number of studies have investigated defenses against herbivores
      in leaves, relatively little is known about defenses in flowers. Using wild
      individuals of 34 species of Asteraceae, we investigated differences in five
      traits that are thought to affect the intensity of herbivory (C, N, P, water, and
      total phenolic contents). Combinations of these traits between flower heads and
      leaves were studied as well. We also evaluated phylogenetic patterns of flower
      head and leaf traits. Flower heads had higher P and lower total phenolics than
      leaves. Water and C contents were negatively correlated both in the flower heads
      and leaves. N, P, and water contents were positively correlated in the flower
      heads, whereas this pattern was not found in the leaves. Thus, the traits we
      measured were more tightly inter-correlated in flower heads than in leaves.
      Because the flower heads had a lower total phenolic content, the relative
      allocation of defensive compounds could not be explained solely by fitness values
      of the organs. Perhaps plants employ an escape strategy rather than a defense
      strategy to cope with floral herbivores and higher allocation in P may enhance
      their escape from herbivores by improving the growth rate of flower heads, though
      our result might be affected in part by the plasticity of plants growing at
      different sites. Moreover, we found weak phylogenetic signals in the defensive
      traits. Because we found significant differences in the flower head traits, these
      weak signals may imply that the traits we measured evolved frequently. 

PMID- 24036933
TI  - Low global sensitivity of metabolic rate to temperature in calcified marine
      invertebrates.
AB  - Metabolic rate is a key component of energy budgets that scales with body size
      and varies with large-scale environmental geographical patterns. Here we conduct
      an analysis of standard metabolic rates (SMR) of marine ectotherms across a 70
      degrees  latitudinal gradient in both hemispheres that spanned collection
      temperatures of 0-30  degrees C. To account for latitudinal differences in the
      size and skeletal composition between species, SMR was mass normalized to that of
      a standard-sized (223 mg) ash-free dry mass individual. SMR was measured for 17
      species of calcified invertebrates (bivalves, gastropods, urchins and
      brachiopods), using a single consistent methodology, including 11 species whose
      SMR was described for the first time. SMR of 15 out of 17 species had a mass
      scaling exponent between 2/3 and 1, with no greater support for a 3/4 rather than
      a 2/3 scaling exponent. After accounting for taxonomy and variability in
      parameter estimates among species using variance-weighted linear mixed effects
      modelling, temperature sensitivity of SMR had an activation energy (Ea) of 0.16
      for both Northern and Southern Hemisphere species which was lower than predicted
      under the metabolic theory of ecology (Ea 0.2-1.2 eV). Northern Hemisphere
      species, however, had a higher SMR at each habitat temperature, but a lower mass
      scaling exponent relative to SMR. Evolutionary trade-offs that may be driving
      differences in metabolic rate (such as metabolic cold adaptation of Northern
      Hemisphere species) will have important impacts on species abilities to respond
      to changing environments.

PMID- 24036934
TI  - Seminal vesicle biopsies: an useful staging procedure-exposure of seminal vesicle
      biopsies protocol and review of the literature.
AB  - BACKGROUND AND OBJECTIVES: Although new MRI techniques have a high sensitivity
      but varying specificity with regard to diagnosing the seminal vesicle invasion
      (SVI) of prostate cancer, the low availability and high cost involved demands
      incorporating an inexpensive and accessible technique that might support adequate
      staging. Currently, uniformity does not exist with regard to the indication
      criteria of seminal vesicle biopsies (SVBs). Our objective is to analyse the
      protocol of SVBs at Morales Meseguer Hospital and conduct an exhaustive review of
      the literature in this field. METHODS AND MATERIALS: SVBs were performed in
      patients who were amenable to a curative treatment and who showed at least one of
      the following indication criteria: prostate-specific antigen greater than or
      equal to 15 ng/ml, a prostate cancer nodule in the base of the prostate, or
      ultrasound abnormalities suggestive of vesicular involvement. SVBs were performed
      in 70 patients. RESULTS: These results revealed a rate of SVI of 15.7 and 25.58 %
      among all patients and patients diagnosed with prostate cancer, respectively. All
      biopsied patients who tested positive for the three indication criteria had T3b
      prostate cancer. Patients with a prostate cancer that altered the base of the
      prostate according to either digital rectal examination or ultrasound showed a
      T3b rate of 53.8 %. CONCLUSIONS: SVBs should be considered a complementary
      procedure for prostate cancer staging because provide important information and
      it is easy, inexpensive and has few complications.

PMID- 24036935
TI  - QT dispersion predicts mortality and correlates with both coronary artery
      calcification and atherosclerosis in hemodialysis patients.
AB  - PURPOSE: QT dispersion (QTd) was shown to be an independent predictor of
      mortality in hemodialysis (HD) patients. It may be hypothesized that coronary
      artery calcification is related to QTd in HD patients because widespread
      calcification may also involve the cardiac conducting system in these patients.
      In this study, we aimed to investigate the relationships of corrected QTd (QTcd)
      with coronary artery calcification score (CACS), carotid plaque score (CPS) and
      possible influence of these parameters on survival of HD patients. METHODS:
      Seventy-two HD patients (33 male, 39 female) were enrolled into the study. Mean
      age of the patients was 44 +/- 12 years. Mean follow-up duration was 77 +/- 24
      months. CACS was determined by computed tomography. QTcd values were calculated
      as the difference of maximum and minimum QT intervals. Left ventricular mass
      index (LVMI) and CPS were measured by echocardiography. RESULTS: QTcd was
      significantly correlated with CACS (r = 0.233, p = 0.049), CPS (r = 0.354, p =
      0.003) and LVMI (p = 0.011, r = 0.299). CPS was found to be significantly higher
      in the group with high QTcd (>60 ms) [2 (1-4) versus 0 (0-1), p = 0.02]. CACS was
      significantly correlated with age (r = 0.44, p < 0.001), LVMI (r = 0.52, p <
      0.001) and CPS (r = 0.32, p = 0.003). In Kaplan-Meier analysis, survival of
      patients with high QTcd was significantly lower than the patients with low QTcd.
      In Cox regression analysis for predicting mortality, age, serum albumin and QTcd
      were found to be the independent predictors of mortality. CONCLUSIONS: QTcd
      independently predicted mortality, and it was significantly associated with
      coronary artery calcification, left ventricular hypertrophy and atherosclerosis
      in HD patients.

PMID- 24036936
TI  - Troponin T and N-terminal pro-B-type natriuretic peptide: a biomarker approach to
      predict heart failure risk--the atherosclerosis risk in communities study.
AB  - BACKGROUND: Among the various cardiovascular diseases, heart failure (HF) is
      projected to have the largest increases in incidence over the coming decades;
      therefore, improving HF prediction is of significant value. We evaluated whether
      cardiac troponin T (cTnT) measured with a high-sensitivity assay and N-terminal
      pro-B-type natriuretic peptide (NT-proBNP), biomarkers strongly associated with
      incident HF, improve HF risk prediction in the Atherosclerosis Risk in
      Communities (ARIC) study. METHODS: Using sex-specific models, we added cTnT and
      NT-proBNP to age and race ("laboratory report" model) and to the ARIC HF model
      (includes age, race, systolic blood pressure, antihypertensive medication use,
      current/former smoking, diabetes, body mass index, prevalent coronary heart
      disease, and heart rate) in 9868 participants without prevalent HF; area under
      the receiver operating characteristic curve (AUC), integrated discrimination
      improvement, net reclassification improvement (NRI), and model fit were
      described. RESULTS: Over a mean follow-up of 10.4 years, 970 participants
      developed incident HF. Adding cTnT and NT-proBNP to the ARIC HF model
      significantly improved all statistical parameters (AUCs increased by 0.040 and
      0.057; the continuous NRIs were 50.7% and 54.7% in women and men, respectively).
      Interestingly, the simpler laboratory report model was statistically no different
      than the ARIC HF model. CONCLUSIONS: cTnT and NT-proBNP have significant value in
      HF risk prediction. A simple sex-specific model that includes age, race, cTnT,
      and NT-proBNP (which can be incorporated in a laboratory report) provides a good
      model, whereas adding cTnT and NT-proBNP to clinical characteristics results in
      an excellent HF prediction model.

PMID- 24036937
TI  - Sandwich assay for mixed-sequence recognition of double-stranded DNA: invader
      based detection of targets specific to foodborne pathogens.
AB  - A 96-well plate sandwich assay based on Invader capture/signalling probes is used
      to recognize 28-mer mixed-sequence dsDNA targets specific to Salmonella enterica,
      Campylobacter jejuni, Escherichia coli. Targets are detected down to 20-55 pM
      concentration with excellent binding specificity. 

PMID- 24036938
TI  - SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-kappaB
      pathway.
AB  - Chronic inflammation induced by amyloid-beta (Abeta) plays a key role in the
      development of age-related macular degeneration (AMD), and matrix
      metalloproteinase-9 (MMP-9), interleukin (IL)-6, and IL-8 may be associated with
      chronic inflammation in AMD. Sirtuin 1 (SIRT1) regulates inflammation via
      inhibition of nuclear factor-kappa B (NF-kappaB) signaling, and resveratrol has
      been reported to prevent Abeta-induced retinal degeneration; therefore, we
      investigated whether this action was mediated via activation of SIRT1 signaling.
      Human adult retinal pigment epithelial (RPE) cells were exposed to Abeta, and
      overactivation and knockdown of SIRT1 were performed to investigate whether SIRT1
      is required for abrogating Abeta-induced inflammation. We found that Abeta
      induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9 were
      abrogated by the SIRT1 activator SRT1720, whereas alterations induced by Abeta in
      SIRT1-silenced RPE cells were not attenuated by SRT1720. In addition, SRT1720
      inhibited Abeta-mediated NF-kappaB activation and decrease of the NF-kappaB
      inhibitor, IkappaBalpha. Our findings suggest a protective role for SIRT1
      signaling in Abeta-dependent retinal degeneration and inflammation in AMD.

PMID- 24036939
TI  - Overexpression of hsa-miR-125b during osteoblastic differentiation does not
      influence levels of Runx2, osteopontin, and ALPL gene expression.
AB  - Multipotent mesenchymal stromal cells (MSCs) were first isolated from bone marrow
      and then from various adult tissues including placenta, cord blood, deciduous
      teeth, and amniotic fluid. MSCs are defined or characterized by their ability to
      adhere to plastic, to express specific surface antigens, and to differentiate
      into osteogenic, chondrogenic, adipogenic, and myogenic lineages. Although the
      molecular mechanisms that control MSC proliferation and differentiation are not
      well understood, the involvement of microRNAs has been reported. In the present
      study, we investigated the role of miR-125b during osteoblastic differentiation
      in humans. We found that miR-125b increased during osteoblastic differentiation,
      as well as Runx2 and ALPL genes. To study whether the gain or loss of miR-125b
      function influenced osteoblastic differentiation, we transfected MSCs with pre
      miR-125b or anti-miR-125b and cultured the transfected cells in an osteoblastic
      differentiation medium. After transfection, no change was observed in
      osteoblastic differentiation, and Runx2, OPN, and ALPL gene expression were not
      changed. These results suggest that the gain or loss of miR-125b function does
      not influence levels of Runx2, OPN, and ALPL during osteoblastic differentiation.

PMID- 24036940
TI  - Tumor growth reduction is regulated at the gene level in Walker 256 tumor-bearing
      rats supplemented with fish oil rich in EPA and DHA.
AB  - We investigated the effect of fish oil (FO) supplementation on tumor growth,
      cyclooxygenase 2 (COX-2), peroxisome proliferator-activated receptor gamma
      (PPARgamma), and RelA gene and protein expression in Walker 256 tumor-bearing
      rats. Male Wistar rats (70 days old) were fed with regular chow (group W) or chow
      supplemented with 1 g/kg body weight FO daily (group WFO) until they reached 100
      days of age. Both groups were then inoculated with a suspension of Walker 256
      ascitic tumor cells (3 * 10(7) cells/mL). After 14 days the rats were killed,
      total RNA was isolated from the tumor tissue, and relative mRNA expression was
      measured using the 2(-DeltaDeltaCT) method. FO significantly decreased tumor
      growth (W=13.18 +/- 1.58 vs WFO=5.40 +/- 0.88 g, P<0.05). FO supplementation also
      resulted in a significant decrease in COX-2 (W=100.1 +/- 1.62 vs WFO=59.39 +/-
      5.53, P<0.001) and PPARgamma (W=100.4 +/- 1.04 vs WFO=88.22 +/- 1.46, P<0.05)
      protein expression. Relative mRNA expression was W=1.06 +/- 0.022 vs WFO=0.31 +/-
      0.04 (P<0.001) for COX-2, W=1.08 +/- 0.02 vs WFO=0.52 +/- 0.08 (P<0.001) for
      PPARgamma, and W=1.04 +/- 0.02 vs WFO=0.82 +/- 0.04 (P<0.05) for RelA. FO reduced
      tumor growth by attenuating inflammatory gene expression associated with
      carcinogenesis.

PMID- 24036941
TI  - Macular pigment optical density in aging eye.

PMID- 24036942
TI  - Calibration of histological retina specimens after fixation in Margo's solution
      and paraffin embedding to in-vivo dimensions, using photography and optical
      coherence tomography.
AB  - BACKGROUND: The extent of retinal tissue deformation by histological processing
      needs to be separately measured for every workup protocol. This work presents a
      simple approach for its quantitative assessment, and shows lateral and axial
      scaling factors for a common protocol. We calibrated histological measurements by
      in-vivo photographic and optical coherence tomographic (OCT) measurements, using
      retinal photocoagulation lesions as calibration markers. METHODS: We evaluated
      four rabbit eyes that were examined histologically after fixation in Margo's
      solution (1 % paraformaldehyde:1.25 % glutaraldehyde), isopropanol dehydration,
      paraffin embedding and hematoxylin and eosin staining. Distances between 51 pairs
      of laser lesions were compared in photographs and on histological slides. Retinal
      thickness measurements were performed at 15 anatomically defined sites in these
      eyes, and related to anatomically matched OCT thickness measurements of six
      different rabbit eyes. RESULTS: We found that the ratio of histological over
      photographic lesion distances was 1.17 (95 % CI 1.13-1.22), indicating 17 %
      lateral retinal stretching or expansion by the processing. Thickness measurements
      in histology were 65.6 % of the in-vivo thickness as measured in OCT, indicating
      1/3 axial tissue compression or shrinkage. CONCLUSIONS: We provide an analysis of
      retinal tissue deformation after fixation in Margo's solution and paraffin
      embedding. In spite of protocol optimization for reduced tissue deformation, the
      workup caused 1/3 axial compression/shrinkage and 17 % lateral elongation, which
      was unexpected. We show a simple way how to calibrate retina specimens by fundus
      photography and OCT, two methods that are readily available to most
      ophthalmologists. Our findings underline the necessity to calibrate specimens
      prior to morphometry.

PMID- 24036943
TI  - [Evaluation of intrauterine death: importance of examination of fetal, placental
      and maternal factors].
AB  - AIMS: Intrauterine death is a multifactorial major complication during pregnancy.
      In this retrospective analysis the pathological anatomical findings of fetuses
      and placentas as well as maternal factors were evaluated. MATERIAL AND METHODS: A
      retrospective screening of post-mortem examinations, corresponding placental
      examinations and clinical data on maternal status (1998-2008) was carried out. A
      classification of all findings was made with the ReCoDe system and induced
      abortions and cases with incomplete data were excluded from the study. RESULTS: A
      total of 84 pregnancies involving 87 fetuses (9 siblings) were evaluated. The
      median gestation age was 20 weeks (range 12-41). The evaluation based on the
      ReCoDe system revealed that intrauterine death was mainly associated with
      placental diseases (n = 63) and to a lesser extent with fetal malformations (n =
      15) or maternal diseases (n = 4). Idiopathic cases were rare (n = 2).
      CONCLUSIONS: Placental examination is important for explaining intrauterine death
      because in most cases an association with placental diseases can be found but
      fetal malformation and maternal diseases must be taken into account.

PMID- 24036944
TI  - Fibrous dysplasia, shepherd's crook deformity and an intra-capsular femoral neck
      fracture.
AB  - Fibrous dysplasia (FD) is a rare bone disorder in which normal medullary bone is
      replaced by fibro-osseous tissue. It typically presents in childhood with pain,
      skeletal deformities, gait abnormalities and occasionally, fatigue fractures. The
      management of FD remains a challenge. Surgical procedures have been developed to
      provide symptom relief, correct skeletal deformity and offer mechanical support
      in cases at risk of fracture. However, there is a paucity of data on the
      management of acute femoral neck fractures in the adult population with FD. We
      report the case of a 23-year-old man with a shepherd's crook deformity secondary
      to FD, who sustained an intra-capsular femoral neck fracture whilst playing
      football. The patient initially underwent closed reduction and internal fixation
      with cannulated screws. However, during the procedure, a guide wire broke whilst
      inside the femoral head. The patient was referred to the senior author, who
      undertook a second operation to remove the metalwork and correct the varus
      deformity using a closing-wedge femoral osteotomy, whilst achieving
      osteosynthesis at the fracture site. At 1-year follow-up, the patient is pain
      free and demonstrates a full range of movement. These cases can be technically
      demanding and carry a greater risk of complication. It is important that
      preoperative planning is undertaken and surgery performed by individuals with
      experience in managing FD and complex femoral neck fractures. Correction of the
      skeletal deformity whilst fixing the fracture will help restore the mechanical
      axis and reduce the risk of a recurrent fracture. 

PMID- 24036945
TI  - Pharmacological targeting of eIF4E in primary CLL lymphocytes.

PMID- 24036946
TI  - Acute promyelocytic leukemias share cooperative mutations with other myeloid
      leukemia subgroups.

PMID- 24036947
TI  - Long-term survival in multiple myeloma is associated with a distinct
      immunological profile, which includes proliferative cytotoxic T-cell clones and a
      favourable Treg/Th17 balance.
AB  - Despite improved outcomes in multiple myeloma (MM), a cure remains elusive.
      However, even before the current therapeutic era, 5% of patients survived >10
      years and we propose that immune factors contribute to this longer survival. We
      identified patients attending our clinic, who had survived >10 years (n=20) and
      analysed their blood for the presence of T-cell clones, T-regulatory cells
      (Tregs) and T helper 17 (Th17) cells. These results were compared with MM
      patients with shorter follow-up and age-matched healthy control donors. The
      frequency of cytotoxic T-cell clonal expansions in patients with <10 years follow
      up (MM patients) was 54% (n=144), whereas it was 100% (n=19/19) in the long
      survivors (LTS-MM). T-cell clones from MM patients proliferated poorly in vitro,
      whereas those from LTS-MM patients proliferated readily (median proliferations
      6.1% and 61.5%, respectively (P<0.0001)). In addition, we found significantly
      higher Th17 cells and lower Tregs in the LTS-MM group when compared with the MM
      group. These results indicate that long-term survival in MM is associated with a
      distinct immunological profile, which is consistent with decreased immune
      suppression. 

PMID- 24036948
TI  - A de novo gain-of-function mutation in SCN11A causes loss of pain perception.
AB  - The sensation of pain protects the body from serious injury. Using exome
      sequencing, we identified a specific de novo missense mutation in SCN11A in
      individuals with the congenital inability to experience pain who suffer from
      recurrent tissue damage and severe mutilations. Heterozygous knock-in mice
      carrying the orthologous mutation showed reduced sensitivity to pain and self
      inflicted tissue lesions, recapitulating aspects of the human phenotype. SCN11A
      encodes Nav1.9, a voltage-gated sodium ion channel that is primarily expressed in
      nociceptors, which function as key relay stations for the electrical transmission
      of pain signals from the periphery to the central nervous system. Mutant Nav1.9
      channels displayed excessive activity at resting voltages, causing sustained
      depolarization of nociceptors, impaired generation of action potentials and
      aberrant synaptic transmission. The gain-of-function mechanism that underlies
      this channelopathy suggests an alternative way to modulate pain perception.

PMID- 24036950
TI  - A rare nonsynonymous sequence variant in C3 is associated with high risk of age
      related macular degeneration.
AB  - Through whole-genome sequencing of 2,230 Icelanders, we detected a rare
      nonsynonymous SNP (minor allele frequency = 0.55%) in the C3 gene encoding a
      p.Lys155Gln substitution in complement factor 3, which, following imputation into
      a set of Icelandic cases with age-related macular degeneration (AMD) and
      controls, associated with disease (odds ratio (OR) = 3.45; P = 1.1 * 10(-7)).
      This signal is independent of the previously reported common SNPs in C3 encoding
      p.Pro314Leu and p.Arg102Gly that associate with AMD. The association of
      p.Lys155Gln was replicated in AMD case-control samples of European ancestry with
      OR = 4.22 and P = 1.6 * 10(-10), resulting in OR = 3.65 and P = 8.8 * 10(-16) for
      all studies combined. In vitro studies have suggested that the p.Lys155Gln
      substitution reduces C3b binding to complement factor H, potentially creating
      resistance to inhibition by this factor. This resistance to inhibition in turn is
      predicted to result in enhanced complement activation.

PMID- 24036949
TI  - Identification of a rare coding variant in complement 3 associated with age
      related macular degeneration.
AB  - Macular degeneration is a common cause of blindness in the elderly. To identify
      rare coding variants associated with a large increase in risk of age-related
      macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10
      candidate loci (57 genes). To increase power, we augmented our control set with
      ancestry-matched exome-sequenced controls. An analysis of coding variation in
      2,268 AMD cases and 2,268 ancestry-matched controls identified 2 large-effect
      rare variants: previously described p.Arg1210Cys encoded in the CFH gene (case
      frequency (fcase) = 0.51%; control frequency (fcontrol) = 0.02%; odds ratio (OR)
      = 23.11) and newly identified p.Lys155Gln encoded in the C3 gene (fcase = 1.06%;
      fcontrol = 0.39%; OR = 2.68). The variants suggest decreased inhibition of C3 by
      complement factor H, resulting in increased activation of the alternative
      complement pathway, as a key component of disease biology.

PMID- 24036951
TI  - Dampening of expression oscillations by synchronous regulation of a microRNA and
      its target.
AB  - The complexity of multicellular organisms requires precise spatiotemporal
      regulation of gene expression during development. We find that in the nematode
      Caenorhabditis elegans approximately 2,000 transcripts undergo expression
      oscillations synchronized with larval transitions while thousands of genes are
      expressed in temporal gradients, similar to known timing regulators. By counting
      transcripts in individual worms, we show that pulsatile expression of the
      microRNA (miRNA) lin-4 maintains the temporal gradient of its target lin-14 by
      dampening its expression oscillations. Our results demonstrate that this
      insulation is optimal when pulsatile expression of the miRNA and its target is
      synchronous. We propose that such a miRNA-mediated incoherent feed-forward loop
      is a potent filter that prevents the propagation of potentially deleterious
      fluctuations in gene expression during the development of an organism.

PMID- 24036953
TI  - Effect of donor-acceptor orientation on solvent-dependent three-photon activity
      in through-space charge-transfer systems--case study of [2,2]-paracyclophane
      derivatives.
AB  - We study the effect of donor-acceptor orientation on solvent-dependent three
      photon transition probabilities (delta(3PA)) of representative through-space
      charge-transfer (TSCT) systems, namely, doubly positively charged [2,2]
      paracyclophane derivatives. Our cubic response calculations reveal that the value
      of delta(3PA) may be as high as 10(6) a.u., which can further be increased by a
      specific orientation of the donor-acceptor moieties. To explain the origin of the
      solvent cum orientation dependency of delta(3PA), we have calculated different
      three-photon tensor components using a two-state model, noting that only a few
      tensor elements contribute significantly to the overall delta(3PA) value. We show
      that this dependence is due to the large dipole moment difference between the
      ground and excited states of the systems. The dominance of a few tensor elements
      indicates a synergistic involvement of pi-conjugation and TSCT in the large
      delta(3PA) of these systems. 

PMID- 24036952
TI  - Rare variants in CFI, C3 and C9 are associated with high risk of advanced age
      related macular degeneration.
AB  - To define the role of rare variants in advanced age-related macular degeneration
      (AMD) risk, we sequenced the exons of 681 genes within all reported AMD loci and
      related pathways in 2,493 cases and controls. We first tested each gene for
      increased or decreased burden of rare variants in cases compared to controls. We
      found that 7.8% of AMD cases compared to 2.3% of controls are carriers of rare
      missense CFI variants (odds ratio (OR) = 3.6; P = 2 * 10(-8)). There was a
      predominance of dysfunctional variants in cases compared to controls. We then
      tested individual variants for association with disease. We observed significant
      association with rare missense alleles in genes other than CFI. Genotyping in
      5,115 independent samples confirmed associations with AMD of an allele in C3
      encoding p.Lys155Gln (replication P = 3.5 * 10(-5), OR = 2.8; joint P = 5.2 * 10(
      9), OR = 3.8) and an allele in C9 encoding p.Pro167Ser (replication P = 2.4 * 10(
      5), OR = 2.2; joint P = 6.5 * 10(-7), OR = 2.2). Finally, we show that the allele
      of C3 encoding Gln155 results in resistance to proteolytic inactivation by CFH
      and CFI. These results implicate loss of C3 protein regulation and excessive
      alternative complement activation in AMD pathogenesis, thus informing both the
      direction of effect and mechanistic underpinnings of this disorder.

PMID- 24036954
TI  - Detecting evolutionary strata on the human x chromosome in the absence of
      gametologous y-linked sequences.
AB  - Mammalian sex chromosomes arose from a pair of homologous autosomes that
      differentiated into the X and Y chromosomes following a series of recombination
      suppression events between the X and Y. The stepwise recombination suppressions
      from the distal long arm to the distal short arm of the chromosomes are reflected
      as regions with distinct X-Y divergence, referred to as evolutionary strata on
      the X. All current methods for stratum detection depend on X-Y comparisons but
      are severely limited by the paucity of X-Y gametologs. We have developed an
      integrative method that combines a top-down, recursive segmentation algorithm
      with a bottom-up, agglomerative clustering algorithm to decipher compositionally
      distinct regions on the X, which reflect regions of unique X-Y divergence. In
      application to human X chromosome, our method correctly classified a concatenated
      set of 35 previously assayed X-linked gene sequences by evolutionary strata. We
      then extended our analysis, applying this method to the entire sequence of the
      human X chromosome, in an effort to define stratum boundaries. The boundaries of
      more recently formed strata on X-added region, namely the fourth and fifth
      strata, have been defined by previous studies and are recapitulated with our
      method. The older strata, from the first up to the third stratum, have remained
      poorly resolved due to paucity of X-Y gametologs. By analyzing the entire X
      sequence, our method identified seven evolutionary strata in these ancient
      regions, where only three could previously be assayed, thus demonstrating the
      robustness of our method in detecting the evolutionary strata. 

PMID- 24036955
TI  - Neurotranmission systems as targets for toxicants: a review.
AB  - Neurotransmitters are chemicals that transmit impulses from one nerve to another
      or from nerves to effector organs. Numerous neurotransmitters have been described
      in mammals, amongst them acetylcholine, amino acids, amines, peptides and gases.
      Toxicants may interact with various parts of neurotransmission systems, including
      synthetic and degradative enzymes, presynaptic vesicles and the specialized
      receptors that characterize neurotransmission systems. Important toxicants acting
      on the cholinergic system include the anticholinesterases (organophosphates and
      carbamates) and substances that act on receptors such as nicotine and the
      neonicotinoid insecticides, including imidacloprid. An important substance acting
      on the glutamatergic system is domoic acid, responsible for amnesic shellfish
      poisoning. 4-Aminobutyric acid (GABA) and glycine are inhibitory
      neurotransmitters and their antagonists, fipronil (an insecticide) and strychnine
      respectively, are excitatory. Abnormalities of dopamine neurotransmission occur
      in Parkinson's disease, and a number of substances that interfere with this
      system produce Parkinsonian symptoms and clinical signs, including notably 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which is the precursor of 1-methyl-4
      phenylpyridinium. Fewer substances are known that interfere with adrenergic,
      histaminergic or seroninergic neurotransmission, but there are some examples.
      Among peptide neurotransmission systems, agonists of opioids are the only well
      known toxic compounds. 

PMID- 24036956
TI  - The N-terminal region containing the zinc finger domain of tobacco streak virus
      coat protein is essential for the formation of virus-like particles.
AB  - Tobacco streak virus (TSV), a member of the genus Ilarvirus (family
      Bromoviridae), has a tripartite genome and forms quasi-isometric virions. All
      three viral capsids, encapsidating RNA 1, RNA 2 or RNA 3 and subgenomic RNA 4,
      are constituted of a single species of coat protein (CP). Formation of virus-like
      particles (VLPs) could be observed when the TSV CP gene was cloned and the
      recombinant CP (rCP) was expressed in E. coli. TSV VLPs were found to be
      stabilized by Zn(2+) ions and could be disassembled in the presence of 500 mM
      CaCl2. Mutational analysis corroborated previous studies that showed that an N
      terminal arginine-rich motif was crucial for RNA binding; however, the results
      presented here demonstrate that the presence of RNA is not a prerequisite for
      assembly of TSV VLPs. Instead, the N-terminal region containing the zinc finger
      domain preceding the arginine-rich motif is essential for assembly of these VLPs.

PMID- 24036958
TI  - Psychometric properties of the 8-item Chronic Pain Acceptance Questionnaire (CPAQ
      8) in a Swedish chronic pain cohort.
AB  - BACKGROUND: Acceptance and Commitment Therapy for chronic pain has good empirical
      support. Pain acceptance is most often assessed with the Chronic Pain Acceptance
      Questionnaire (CPAQ). Recently a shorter 8-item version, the CPAQ-8, was
      developed. OBJECTIVES: To further validate the CPAQ-8 in a Swedish context and to
      test its sensitivity to treatment effects, an as-yet unknown property of the
      instrument. METHODS: A total of 891 patients completed the CPAQ, along with
      scales for anxiety and depression (Hospital Anxiety and Depression scale),
      kinesiophobia (Tampa Scale for Kinesiophobia) and quality of life (Short Form
      36). Confirmatory factor analyses were performed to examine the factor structure.
      Convergent validity was tested with Pearson's correlations. Changes over time
      were evaluated with paired t-test. RESULTS: The confirmatory factor analyses
      showed that the CPAQ 2-factor model had a better fit compared with the 1-factor
      model, both for the 8- and 20-item versions. All CPAQ-8 scales demonstrated good
      internal consistency (alpha >= 0.80). They also correlated significantly with
      related constructs, supporting convergent validity. The CPAQ-8 explained a large
      share of the total variance in CPAQ-20 and was also able to track rehabilitation
      changes (large effect size, d = 0.89). CONCLUSION: CPAQ-8 demonstrated good
      psychometric properties and sensitivity to rehabilitation changes. Further
      research that considers other cultural contexts may lead enhance the applications
      of this instrument.

PMID- 24036959
TI  - Voices across Kansas: community health assessment and improvement efforts among
      local health departments.
AB  - CONTEXT: Community health assessment (CHA) and community health improvement
      planning (CHIP) is central to public health accreditation and essential functions
      and therefore important to local health departments (LHDs). However, rural states
      face significant challenges to pursue public health accreditation. OBJECTIVE: The
      purpose of this statewide study was to identify factors that impede or promote
      the timeliness of CHA and CHIP completion. DESIGN: Fifteen focus groups,
      representing 11 of 15 public health regions, were conducted via telephone, using
      a structured interview script between April and September 2012. SETTING: The
      sampling frame for the project was represented by counties in Kansas that planned
      to conduct a CHA-CHIP activity during 2012. PARTICIPANTS: Participants (N = 76)
      were LHD administrators, hospital representatives, and key community stakeholders
      from frontier, rural, and urban settings who were involved in CHA-CHIP
      activities. They were predominantly female (86.0%) and 51 years or older (66.7%).
      MAIN OUTCOME MEASURES: The study assessed perceptions and opinions about the
      inputs, process, outputs, and outcomes of CHA-CHIP activities within the
      community. RESULTS: Overall, CHA-CHIP implementation in Kansas was in its early
      stages. Rural counties reported a lack of capacity and confidence to perform many
      CHA-CHIP activities. Early CHA-CHIP adopters were located in more populous,
      metropolitan areas and had progressed further into the CHA-CHIP process.
      Regardless of rural/urban status, a history of collaborative activity among
      community stakeholder groups appeared to promote progress in CHA-CHIP completion.
      Participants reported that additional funding, time, trained staff, technical
      assistance, and community leadership were needed to conduct CHA-CHIP activities.
      Barriers included maintaining required LHD services while conducting assessment
      and planning activities and differences in public health and federal cycles for
      performing CHA. CONCLUSIONS: Study findings have implications for strengthening
      rural workforce development and technical assistance for CHA-CHIP activities.

PMID- 24036960
TI  - Use of the community assessment for public health emergency response to conduct
      community health assessments for public health accreditation.
AB  - A community health assessment (CHA) is a collaborative process of collecting and
      analyzing data to learn about the health status of a community. Community health
      assessments are also a requirement of public health accreditation for state and
      local health departments and of the Affordable Care Act for nonprofit hospitals.
      One element of a CHA is primary data collection. This article describes the use
      of the Community Assessment for Public Health Emergency Response (CASPER) method
      for primary data collection to meet public health accreditation requirements in 2
      case study communities--Nashua, New Hampshire, and Davidson County, North
      Carolina; CASPER is a flexible and efficient method for the collection of
      population-based primary data in an urban or rural setting.

PMID- 24036961
TI  - Reward sensitivity to faces versus objects in children: an ERP study.
AB  - How children respond to social and nonsocial rewards has important implications
      for understanding social cognitive development. Adults find faces intrinsically
      rewarding. However, little is known about how children respond to face vs nonface
      rewards. We utilized event-related potentials (the stimulus-preceding negativity,
      SPN) to measure differences in reward anticipation during a guessing game in 6-
      to 8-year-olds. Children were presented with reward indicators accompanied by
      incidental face or nonface stimuli. Nonface stimuli were comprised of scrambled
      faces in the shape of arrows, controlling for low-level properties of the two
      conditions. Children showed an increased SPN when the reward stimuli were
      accompanied by faces, relative to nonface stimuli. This suggests that children
      find a face stimulus more rewarding than a nonface stimulus. The results have
      important implications for processing social vs nonsocial rewards in typically
      developing children, and allow testing of populations with deficits in social
      reward processing, such as autism spectrum disorder. 

PMID- 24036962
TI  - Sex differences in the persistence of the amygdala response to negative material.
AB  - Previous studies have indicated that men and women have different amygdala
      responses to novel (vs familiar) and valenced (positive vs negative) material. It
      is not known, however, whether these affective sex differences are related. In
      this study, we tested whether women have more persistent amygdala responses to
      familiar, negative material than men do. During fMRI, male and female
      participants viewed evocative images that varied in novelty and valence. Women
      and men showed equivalent responses to novel negative material, but women showed
      a sustained amygdala response to familiar negative material relative to men,
      indicating that women's amygdala responses were more persistent over multiple
      repetitions of negative material. Individuals with more persistent amygdala
      responses also reported greater levels of negative effect. These findings have
      implications for sex differences in the incidence of affective disorders. 

PMID- 24036963
TI  - Changing the mind? Not really-activity and connectivity in the caudate correlates
      with changes of choice.
AB  - Changes in preference are inherently subjective and internal psychological
      events. We have identified brain events that presage ultimate (rather than
      intervening) choices, and signal the finality of a choice. At the first exposure
      to a pair of faces, caudate activity reflected the face of final choice, even if
      an initial choice was different. Furthermore, the orbitofrontal cortex and
      hippocampus exhibited correlations only when the subject had made a choice that
      would not change. 

PMID- 24036971
TI  - Significance of scaling and root planing with and without adjunctive use of a
      water-cooled pulsed Nd:YAG laser for the treatment of periodontal inflammation.
AB  - The aim was to assess the significance of scaling and root planing (SRP) with
      adjunctive use of a water-cooled pulsed neodymium-doped yttrium aluminum garnet
      (Nd:YAG) laser for the treatment of periodontal inflammation. Thirty-nine
      patients were equally divided into three groups. In group 1, the upper jaw was
      treated with Nd:YAG laser application; whereas in groups 2 and 3, the upper jaw
      was treated with SRP alone and Nd:YAG laser application immediately after SRP,
      respectively. In each group, probing pocket depth (PPD), plaque index (PI), and
      gingival index (GI) were measured and gingival crevicular fluid (GCF) volume was
      determined after using at 1 week and after 3 months. Three-month follow-up
      results showed that PPD, PI, GI, and GCF volume were significantly reduced in
      group 3 compared to groups 1 and 2. In short term, SRP with a single application
      of a water-cooled pulsed Nd:YAG laser reduced PI, GI, PPD, and GCF volume more
      significantly compared to when Nd:YAG laser and SRP are used alone to treat
      periodontal inflammation. 

PMID- 24036973
TI  - A low cost, all-organic Na-ion battery based on polymeric cathode and anode.
AB  - Current battery systems have severe cost and resource restrictions, difficultly
      to meet the large scale electric storage applications. Herein, we report an all
      organic Na-ion battery using p-dopable polytriphenylamine as cathode and n-type
      redox-active poly(anthraquinonyl sulphide) as anode, excluding the use of
      transition-metals as in conventional electrochemical batteries. Such a Na-ion
      battery can work well with a voltage output of 1.8 V and realize a considerable
      specific energy of 92 Wh kg(-1). Due to the structural flexibility and stability
      of the redox-active polymers, this battery has a superior rate capability with
      60% capacity released at a very high rate of 16 C (3200 mA g(-1)) and also
      exhibit an excellent cycling stability with 85% capacity retention after 500
      cycles at 8 C rate. Most significantly, this type of all-organic batteries could
      be made from renewable and earth-abundant materials, thus offering a new
      possibility for widespread energy storage applications.

PMID- 24036972
TI  - Structure and function of cytochrome P450S in insect adaptation to natural and
      synthetic toxins: insights gained from molecular modeling.
AB  - Over evolutionary time, insect herbivores have adapted to the presence of natural
      toxins and more recently to synthetic insecticides in or on the plants they
      consume. Biochemical analyses and molecular modeling of the cytochrome P450
      monooxygenases (P450s) that metabolize these compounds have provided insight into
      the many variations affecting their catalytic activity. Phylogenetically distinct
      P450s may metabolize similar substrates, and phylogenetically similar P450s may
      metabolize different substrates; as well, some P450s process broad arrays of both
      phytochemicals and synthetic insecticides, while closely related P450s are
      restricted to a narrow range of phytochemicals. Mapped on the predicted three
      dimensional structures of insect P450s developed from available mammalian P450
      crystal structures, differences in multiple regions of the insect proteins reveal
      the evolutionary processes occurring as P450 genes have duplicated and diverged.
      Analyses of site-directed mutants in select lepidopteran and dipteran P450s
      demonstrate that slight changes in the catalytic site, the putative product
      release channel, and the proximal surface (interacting with electron transfer
      partners such as cytochrome P450 reductase and cytochrome b5) yield pronounced
      activity differences. Additionally, changes in the catalytic site and in the
      linker region preceding the proline-hinge influence P450 folding. With predicted
      structures available for many mammalian P450s involved in metabolism of
      xenobiotics, it is possible to record allelic variation relative to catalytically
      important regions in the overall P450 structure and to predict functionally
      critical differences. Together with information on the relative levels of allelic
      variant transcripts, comprehensive characterization of the mechanisms that
      modulate metabolism of natural and synthetic xenobiotics in insects can yield
      insights into plant-insect coevolution and into novel approaches for chemical
      pest management. 

PMID- 24036974
TI  - Alteration of urinary macromolecules by adsorption on surfaces, probably an
      important factor in urolithiasis.
AB  - To get information on the consequences of adsorption of urinary macromolecules
      (UMs) on crystals, Ca phosphate (CaP) precipitation was performed in urine of 15
      stone patients and 15 controls. In solutions of dissolved precipitates (DPU), Ca
      oxalate (CaOx) crystallization and aggregation (AGN) of latex beads were
      spectrophotometrically studied and compared to results obtained in urine and in
      UMs isolated by hemofilter dialysis (HD). Tests were repeated with a 20 MUg/mL
      albumin solution (AS). Inhibition of CaOx growth and AGN was significantly
      reduced in DPU as well as in HD. Furthermore, DPU and HD showed an AGN of latex
      beads which in patients was more pronounced than in controls. Identical effects
      observed in DPU and HD can be explained by temporary high concentrations of UMs
      by adsorption on surfaces favoring self AGN. Temporary adsorption of AS on CaP
      produced polymers of a limited size, significantly reduced the inhibition of CaOx
      AGN and accelerated latex AGN. In DPU, AGN of latex beads occurred despite a
      surface potential of -37 mV, which within short distances produces areas of
      massive electrostatic repulsion and normally inhibits AGN. Such areas might be
      bridged by self-aggregated UMs. The retardation of CaOx AGN measured in DPU could
      be decisive whether during crystalluria crystals are washed out from the kidney
      by diuresis or are attached to kidney calcifications or pre-existing stones. 

PMID- 24036975
TI  - The academic dimension of university extension programs.

PMID- 24036976
TI  - Bond strength of self-adhesive resin cements to dry and moist dentin.
AB  - This study evaluated the effects of humidity conditions and evaluation times on
      the dentin bond strength (DBS) of two self-adhesive resin cements (RC). The RC
      used were: RelyX Unicem (3M ESPE) and Clearfil SA Cement (Kuraray Med.). One
      hundred and twenty coronal portions of bovine incisors (n = 10) were used. Buccal
      surfaces were abraded in order to expose a flat dentinal surface (180-grit SiC)
      and to standardize the smear layer formation (600-grit SiC). The humidity
      conditions tested were: dry (air-dried for 10 s), slightly moist (water
      application with disposable applicator on dried dentin and water excess removed
      with absorbent paper), and moist (same application without water removal). The RC
      were used according to the manufacturers' recommendations and were applied to
      prepolymerized resin discs (2 mm thick; Sinfony, 3M ESPE), which were
      subsequently bonded to the dentin surfaces. After 24 h, half of the teeth were
      prepared for the microtensile bond strength test, while the other half were
      stored in water for 6 months and tested in tension (0.5 mm/min) until failure. A
      3-way analysis of variance and the Tukey test were performed (preset alpha of
      0.05). No RC showed any reduction of DBS after 6 months, and no significant
      difference was observed between them. The moist dentin increased the bond
      strength of Clearfil SA Cement for both periods of time. Humidity conditions can
      change the DBS; however, the study's results were product-dependent. 

PMID- 24036977
TI  - Evaluation of the adaptation of zirconia-based fixed partial dentures using micro
      CT technology.
AB  - The objective of the study was to measure the marginal and internal fit of
      zirconia-based all-ceramic three-unit fixed partial dentures (FPDs) (Y-TZP -
      LAVA, 3M-ESPE), using a novel methodology based on micro-computed tomography
      (micro-CT) technology. Stainless steel models of prepared abutments were
      fabricated to design FPDs. Ten frameworks were produced with 9 mm2 connector
      cross-sections using a LAVATM CAD-CAM system. All FPDs were veneered with a
      compatible porcelain. Each FPD was seated on the original model and scanned using
      micro-CT. Files were processed using NRecon and CTAn software. Adobe Photoshop
      and Image J software were used to analyze the cross-sectional images. Five
      measuring points were selected, as follows: MG - marginal gap; CA - chamfer area;
      AW - axial wall; AOT - axio-occlusal transition area; OA - occlusal area. Results
      were statistically analyzed by Kruskall-Wallis and Tukey's post hoc test (alpha=
      0.05). There were significant differences for the gap width between the
      measurement points evaluated. MG showed the smallest median gap width (42 um). OA
      had the highest median gap dimension (125 um), followed by the AOT point (105
      um). CA and AW gap width values were statistically similar, 66 and 65 um
      respectively. Thus, it was possible to conclude that different levels of
      adaptation were observed within the FPD, at the different measuring points. In
      addition, the micro-CT technology seems to be a reliable tool to evaluate the fit
      of dental restorations. 

PMID- 24036978
TI  - Influence of the interposition of ceramic spacers on the degree of conversion and
      the hardness of resin cements.
AB  - This study evaluated: I) the effect of photo-activation through ceramics on the
      degree of conversion (DC) and on the Knoop hardness (KHN) of light- and dual
      cured resin cements; and II) two different protocols for obtaining the spectra of
      uncured materials, to determine the DC of a dual-cured resin cement. Thin films
      of cements were photo-activated through ceramics [feldspathic porcelain (FP);
      lithium disilicate glass-ceramics of low translucency (e.max-LT), medium opacity
      (e.max-MO) and high translucency (e.max-HT); glass-infiltrated alumina composite
      (IC) and polycrystalline zirconia (ZR)] with thicknesses of 1.5 and 2.0 mm. DC
      was analyzed by Fourier transform infrared (FTIR) spectroscopy. Two protocols
      were used to obtain the spectra of the uncured materials: I) base and catalyst
      pastes were mixed, and II) thin films of base and catalyst pastes were obtained
      separately, and an average was obtained. KHN assessment was performed with
      cylindrical specimens. The results were analyzed by ANOVA and Tukey's test
      (alpha= 0.05). The light-cured cement showed higher DC (61.9%) than the dual
      cured cement (55.7%). The DC varied as follows: FP (65.4%), e.max-HT (65.1%),
      e.max-LT (61.8%), e.max-MO (60.9%), ZR (54.8%), and IC (44.9%). The light-cured
      cement showed lower KHN (22.0) than the dual-cured (25.6) cement. The cements
      cured under 1.5 mm spacers showed higher KHN (26.2) than when polymerized under
      2.0 mm ceramics (21.3). Regarding the two protocols, there were significant
      differences only in three groups. Thus, both methods can be considered
      appropriate. The physical and mechanical properties of resin cements may be
      affected by the thickness and microstructure of the ceramic material interposed
      during photo-activation. 

PMID- 24036979
TI  - Do new matrix formulations improve resin composite resistance to degradation
      processes?
AB  - The aim of this study was to determine the degradation resistance of three new
      formulations-silorane-, Ormocer- and dimer-acid-based materials-and compare them
      to the traditional dimethacrylate-based materials. One silorane- (Filtek P90,
      P90), one Ormocer- (Ceram-X, CX), one dimer-acid- (N'Durance, ND) and two
      dimethacrylate-based (Filtek P60, P60; Tetric Ceram, TC) materials were
      investigated. Water sorption (Wsp) and solubility (Wsl) were determined after the
      materials were immersed in water for 28 days. Knoop hardness (KH) was determined
      before and after 24 h immersion in pure ethanol. The flexural-strength (FS) was
      determined by the bending test after one-week storage in a dry environment or
      after one-week immersion in pure ethanol. Data were submitted to analysis of
      variance (ANOVA) and Tukey's test (95%). The three new formulations showed lower
      Wsp than the dimethacrylate-based formulation. CX (0.50 +/- 0.17%) and ND (0.72
      +/- 0.19%) exhibited the lowest Wsp, whereas P90 (0.02 +/- 0.03%) and P60 (0.04
      +/- 0.03%) showed the lowest Wsl. All resins showed reduced Knoop hardness number
      (KHN) after ethanol immersion. P60 presented the lowest decrease in KH value (19
      +/- 5%). TC (48 +/- 3%) and P90 (39 +/- 9%) showed the highest KHN decrease after
      ethanol storage. The FS of CX, ND and TC were affected by ethanol storage. The
      new formulations did not improve the degradation resistance, as compared with the
      traditional methacrylate-based materials. 

PMID- 24036980
TI  - Bone healing of mandibular critical-size defects in spontaneously hypertensive
      rats.
AB  - Few articles have shown changes in bone metabolism caused by hypertension. The
      objective of this study was to investigate the relationship between hypertension
      and bone healing. Circular critical-size defects 5 mm and 2 mm in diameter were
      created, respectively, on the left and right side of the mandible in 40
      spontaneously hypertensive and 40 control Wistar-Kyoto rats. Five animals from
      each strain were killed 2, 3, 5, 10, 15, 30, 60 and 90 days after surgery. The
      macroscopic evaluation showed great mandibular angle deformation on the left side
      and non-healed defects on both sides and groups. Histological evaluation revealed
      similar bone healing on both sides, with initial necrosis in the central area,
      and fibrosis and angiogenesis within the first 5 days. From the 10th
      postoperative day on, the newly formed bone displayed progressive thickening
      until the 90th postoperative day, when the defect margins presented a compact
      bone structure. Furthermore, the statistical analysis of the histometric data did
      not reveal any significant hypertension effect on bone healing in the defect
      area. These results suggest that bone healing was not different between
      spontaneously hypertensive rats and control rats. 

PMID- 24036981
TI  - Evaluation of the posterior superior alveolar artery and the maxillary sinus with
      CBCT.
AB  - Assessment of the maxillary sinus anatomy before sinus augmentation is important
      for avoiding surgical complications, because of the close anatomical relationship
      between the posterior maxillary teeth and the maxillary sinus. The posterior
      superior alveolar artery (PSAA) is the branch of the maxillary artery that
      supplies the lateral sinus wall and overlying membrane. We evaluated the location
      of the PSAA and its relationship to the alveolar ridge and maxillary sinus using
      cone beam computed tomography (CBCT). The study group consisted of 135 CBCT scans
      (270 sinuses) obtained from the archive of the dentomaxillofacial radiology
      department at Yeditepe University Faculty of Dentistry, Istanbul, Turkey. The
      distance between the lower border of the artery and the alveolar crest, bone
      height from the sinus floor to the ridge crest, distance from the artery to the
      medial sinus wall, and the diameter and location of the artery were determined.
      The occurrence of septa and pathology were recorded from CBCT scans. The PSAA was
      observed in 89.3% of sinuses, and 71.1% of arteries were intraosseous with
      diameters mostly < 1 mm (68.9%). The prevalence of sinus septa was 55.2%, and
      that of sinus pathology was 57.4%. The mean age was 43.07 +/- 17.55 years. There
      was a statistically significant difference between the location of the artery and
      gender (p < 0.05). The prevalence of sinus membrane thickening was 57.4%.
      Detailed knowledge about the location of the PSAA and sinus morphology may be
      obtained with CBCT before maxillary sinus surgery. 

PMID- 24036982
TI  - Immunohistochemical expression of biglycan and decorin in the pulp tissue of
      human primary teeth during resorption.
AB  - Primary teeth are interesting models that can be used to study physiological and
      pathological processes involving cells and extracellular matrices in hard and
      soft tissues. This study investigated the expression and distribution of biglycan
      and decorin-the non-collagenous components of the extracellular matrix-in primary
      teeth tissue, during physiological root resorption. Thirty healthy human primary
      teeth were grouped together according to root length: Group I - two-thirds root
      length, Group II - one-third root length, and Group III - teeth with no root. The
      streptavidin-biotin-peroxidase immunohistochemical method was used with
      antibodies against the previously named antigens. The proteoglycans studied were
      found in the pulp and dentin extracellular matrix in all groups without any
      differences in the proteins, among the groups. Biglycan was observed mainly in
      predentin and in pulp connective tissue in the resorption area. In addition,
      decorin was observed mainly in pulp connective tissue, but near the resorption
      area. Biglycan and decorin were distributed differentially in the dental tissues.
      The present immunohistocytochemical data, combined with previously reported data,
      suggest that these proteoglycans could be involved in regulating the
      physiological resorption process in healthy primary teeth. 

PMID- 24036983
TI  - Design of oligothiophene-based tetrazoles for laser-triggered photoclick
      chemistry in living cells.
AB  - A 405 nm light-activatable terthiophene-based tetrazole was designed that reacts
      with a fumarate dipolarophile with the second-order rate constant k2 exceeding
      10(3) M(-1) s(-1). The utility of this laser-activatable tetrazole in imaging
      microtubules in a spatiotemporally controlled manner in live cells was
      demonstrated. 

PMID- 24036985
TI  - Detection of diabetic nephropathy from advanced glycation endproducts (AGEs)
      differs in plasma and urine, and is dependent on the method of preparation.
AB  - Increased advanced glycation endproducts (AGEs) and oxidation products (OPs) have
      been proposed as pathogenic for diabetic nephropathy (DN). We investigated the
      relationship between AGEs and OPs measured in different plasma and urine
      preparations, and progression of DN in 103 young, normoalbuminuric, normotensive
      participants with type 1 diabetes in the Natural History of Diabetic Nephropathy
      Study. The primary endpoint was electron microscopy-measured change in glomerular
      basement membrane (GBM) width from baseline to 5 years; change in mesangial
      fractional volume was a secondary endpoint. Fast progressors (FP) were defined as
      the upper quartile (n = 24) of rate of GBM thickening; slow progressors (SP) were
      the remainder (n = 79). Four AGEs [3-deoxyglucosone and methylglyoxal
      hydroimidazolones (DG3H1, MGH1) and carboxymethyl and ethyl lysine (CML, CEL)],
      and two oxidation products methionine sulfoxide and aminoadipic acid were
      measured by liquid chromatography, triple quadrupole mass spectrometry.
      Measurements were done on 10 K plasma filtrates and plasma proteolytic digests
      (PPD) at year 5, and at four time points over 5 years for urinary 10 K filtrates.
      Urinary filtrate CEL levels were significantly higher in FP, but not after
      adjustment for HbA1c, sex, and duration of diabetes. MGHI, CEL, and CML plasma
      filtrate levels were significantly higher in FP relative to SP (p < 0.05). In
      PPD, only MGHI showed borderline significantly higher levels in FP relative to SP
      (p = 0.067), while no other product showed correlation. AGE and OP measurements
      were not correlated with mesangial expansion. In plasma filtrates, HbA1c at year
      5 accounted for 4.7 % of the variation in GBM width. The proportion of variation
      in GBM width was increased to 11.6 % when MGHI, CEL, and CML were added to the
      model (6.9 % increase).

PMID- 24036984
TI  - Low concentrations of niflumic acid enhance basal spontaneous and carbachol
      induced contractions of the detrusor.
AB  - PURPOSE: The urinary bladder expresses Ca(2+)-activated Cl(-) channels (CACC),
      but its physiological role in governing contractility remains to be defined. The
      CACC modulator niflumic acid (NFA) is widely used despite the variable results
      arisen from different drug concentrations used. This study was designed to
      examine the effects of NFA at low concentrations on detrusor strip contractility.
      METHODS: Rat detrusor strips with mucosa-intact (+MU) and mucosa-denuded (-MU)
      were prepared in transverse (Tr) and longitudinal (Lg) with respect to the
      bladder orientation. Isometric force measurements were made at baseline (for
      spontaneous phasic contractile activity) and during drug stimulation (by
      carbachol, CCh) with and without NFA. RESULTS: NFA (1 and 10 MUmol/L)
      pretreatment enhanced CCh-induced contractions more in +MU than -MU strips with
      no selectivity on contractile direction. For spontaneous phasic contractions, NFA
      treated strips in the Tr direction showed increased phasic amplitude, while
      phasic frequency was unchanged. CONCLUSIONS: The findings suggest low
      concentrations of NFA having a potentiating effect on detrusor contractions that
      was sensitive to the MU and contractile direction.

PMID- 24036986
TI  - Three-dimensional environment renders cancer cells profoundly less susceptible to
      a single amino acid starvation.
AB  - Increased amino acid requirement of malignant cells is exploited in metabolic
      antitumor therapy, e.g., enzymotherapies based on arginine or methionine
      deprivation. However, studies on animal models and clinical trials revealed that
      solid tumors are much less susceptible to single amino acid starvation than could
      be expected from the in vitro data. We conducted a comparative analysis of the
      response of several tumor cell lines to single amino acid starvation in 2-D
      monolayer versus 3-D spheroid culture. We revealed for the first time that in
      comparison with monolayer culture tumor cells, spheroids are much less
      susceptible to the deprivation of individual amino acids (i.e., arginine,
      leucine, lysine or methionine). Accordingly, even after prolonged (up to 10 days)
      starvation, spheroid cells could readily resume proliferation when appropriate
      amino acid was resupplemented. In the case of arginine deprivation, similar
      apoptosis induction was detected both in 2-D and 3-D culture, suggesting that
      this process does not determine the level of tumor cell sensitivity to this kind
      of treatment. It was also observed that spheroids much better mimic the in vivo
      ability of tumor cells to utilize citrulline as arginine precursor for growth in
      amino acid deficient environment. We conclude that 3-D spheroid culture better
      reflects in vivo tumor cell response to single amino acid starvation than 2-D
      monolayer culture and should be used as an integral model in the studies of this
      type of antitumor metabolic targeting.

PMID- 24036987
TI  - State-space modelling reveals proximate causes of harbour seal population
      declines.
AB  - Declines in large vertebrate populations are widespread but difficult to detect
      from monitoring data and hard to understand due to a multiplicity of plausible
      biological explanations. In parts of Scotland, harbour seals (Phoca vitulina)
      have been in decline for 10 years. To evaluate the contributions of different
      proximate causes (survival, fecundity, observation artefacts) to this decline, we
      collated behavioural, demographic and population data from one intensively
      studied population in part of the Moray Firth (north-east Scotland). To these, we
      fit a state-space model comprising age-structured dynamics and a detailed account
      of observation errors. After accounting for culling (estimated by our model as
      14% of total mortality), the main driver of the historical population decline was
      a decreasing trend in survival of young individuals combined with (previously
      unrecognised) low levels of pupping success. In more recent years, the model
      provides evidence for considerable increases in breeding success and consistently
      high levels of adult survival. However, breeding success remains the most
      volatile demographic component of the population. Forecasts from the model
      indicate a slow population recovery, providing cautious support for recent
      management measures. Such investigations of the proximate causes of population
      change (survival, fecundity and observation errors) provide valuable short-term
      support for the management of population declines, helping to focus future data
      collection on those ultimate causal mechanisms that are not excluded by the
      demographic evidence. The contribution of specific ultimate drivers (e.g.
      shooting mortality or competitors) can also be quantified by including them as
      covariates to survival or fecundity.

PMID- 24036989
TI  - Overestimation of subfoveal choroidal thickness by measurement based on
      horizontally compressed optical coherence tomography images.

PMID- 24036988
TI  - Changes in toll-like receptor (TLR)4-NFkappaB-IL1beta signaling in male gout
      patients might be involved in the pathogenesis of primary gouty arthritis.
AB  - We undertook this study to determine whether the altered toll-like receptor
      (TLR)4-nuclear factor kappaB (NFkappaB)-interleukin1beta (IL1beta) signaling in
      peripheral blood of gout patients could provide insights into the pathogenesis of
      primary gouty arthritis (GA). TLR4 mRNA, TLR4 and NFkappaBp65 proteins expression
      and IL1beta production were measured in 52 acute GA (AGA) and 34 non-acute GA
      (NAGA) male patients and 78 male healthy subjects (HC). NFkappaBp65
      transcriptional activity and IL1beta production were measured after TLR4
      inhibition with anti-TLR4 antibody in peripheral whole blood from 13 AGA
      patients. The TLR4, NFkappaBp65 and IL1beta expression was significantly
      increased in the AGA group than those in the NAGA or HC group (P < 0.05,
      respectively), also the levels were higher in the NAGA group comparing with those
      in the HC group (P < 0.05, respectively). Furthermore, moderate positive
      correlations were observed between concentration of uric acid and the TLR4 mRNA
      level, serum IL1beta production (r = 0.649, 0.616), and strong positive
      correlation was observed between TLR4 mRNA level and serum IL1beta (r = 0.848) in
      52 AGA patients. On the other hand, NFkappaBp65 level and IL1beta production were
      dramatically reduced after TLR4 blockade with anti-TLR4 antibody in peripheral
      blood from the AGA patients (P < 0.05, respectively). TLR4-NFkappaB-IL1beta
      signaling might play a crucial role in the development of acute inflammation in
      primary gout patients. 

PMID- 24036990
TI  - In vitro FANCD2 monoubiquitination by HHR6 and hRad18.

PMID- 24036991
TI  - Influence of Ag nanoparticles on the luminescence dynamics of Dy3+ ions in glass:
      the "plasmonic diluent" effect.
AB  - This work demonstrates that metallic nanoparticles (NPs) embedded in rare-earth
      (RE) co-doped dielectrics are able to produce an effect analogous to a reduction
      in the effective concentration of the luminescent RE ions in the matrix, herein
      coined the "plasmonic diluent" effect. This has been revealed explicitly for
      Dy(3+) and Ag NP co-doped aluminophosphate glasses, which were investigated using
      optical absorption and photoluminescence (PL) spectroscopy with emphasis on the
      influence of plasmonic NPs on the luminescence decay dynamics of Dy(3+) ions. The
      glasses were prepared using the melt-quenching technique, where the precipitation
      of Ag NPs was subsequently induced by heat treatment (HT). The development of the
      surface plasmon resonance (SPR) band of Ag NPs at around 410 nm resulted in the
      quenching of Dy(3+) emission for the (4)F9/2 -> (6)H15/2, (6)H13/2 transitions
      (484, 574 nm) under resonant excitation of (6)H15/2 -> (4)I15/2 transition at 450
      nm. The decay of the (4)F9/2 excited state was monitored at 574 nm (away from
      SPR) under excitation at 450 nm (within SPR), where the PL dynamics indicated the
      presence of two populations of Dy(3+) ions in the glasses, in connection with
      slow (taus) and fast (tauf) lifetime components. A tendency of the decay times to
      increase gradually with HT holding time was observed as the volume fraction of
      the plasmonic Ag particles increased. The data are interpreted in terms of an ion
      to-particle excitation energy transfer operating via surface plasmons in the
      nanoscale metal. This produces a Dy(3+) deactivation effect analogous to a
      lowering in the effective concentration of emitting Dy(3+) ions in the matrix,
      i.e., the metal NPs play a role as a "plasmonic diluent" in the glass system with
      respect to the luminescent RE ions. 

PMID- 24036993
TI  - Locally advanced gastric cancer complicated by mesenteric invasion and intestinal
      malrotation.

PMID- 24036992
TI  - African-Americans, Hispanic Americans, and non-Hispanic whites without GERD or
      reflux symptoms have equivalent 24-h pH esophageal acid exposure.
AB  - BACKGROUND: Ambulatory esophageal pH monitoring is, currently, the recommended
      diagnostic exam for gastroesophageal reflux disease. Data are currently available
      for African-American (AA) and non-Hispanic white (nHw) volunteers among United
      States ethnic groups. The purpose of this study was to obtain normal values of 24
      h esophageal pH by monitoring healthy adult Hispanic American (HA) volunteers and
      to compare these with values obtained from healthy AA and nHw volunteers to
      determine if ethnic variation exists in 24-h esophageal pH. METHODS: 24-h Dual
      esophageal pH monitoring was performed for healthy AA, HA, and nHw. Values for
      total number of reflux episodes, episodes longer than 5 min, total reflux time,
      and longest reflux episode in the proximal and/or distal esophagus were obtained
      for all groups. Differences between groups were considered significant if p<0.05.
      RESULTS: One-hundred and thirty-six subjects volunteered and completed 24-h pH
      testing. Fifty-three were AA, 25 HA, and 58 nHw, with males accounting for 52,
      47, and 47%, respectively, of each group. AA were older than nHw only and nHw had
      a lower body mass index than both AA and HA. Shorter study duration was observed
      for HA than for AA and nHw. No difference was observed between ethnic groups for
      any measured pH data in the proximal or distal esophagus. CONCLUSIONS: No
      difference exists in values obtained during esophageal pH monitoring among
      healthy AA, HA, and nHw. This indicates that currently accepted normal values of
      ambulatory esophageal pH monitoring can be used for all major United States
      ethnic groups without compromising diagnostic accuracy.

PMID- 24036994
TI  - Morbidity in children and adolescents after surgical correction of interrupted
      aortic arch.
AB  - Previous studies of outcome after operative correction of interrupted aortic arch
      (IAA) have focused on mortality and rates of reintervention. We sought to
      investigate the clinical status of children and adolescents after surgery for
      IAA. A cross-sectional study of subjects with IAA between the ages of 8 and 18
      years was performed with the subjects undergoing simultaneous genetic testing,
      electrocardiogram, cardiac magnetic resonance imaging, cardiopulmonary exercise
      testing, and assessment of health status and health-related quality of life as
      well as concurrent retrospective cohort study reviewing their postoperative use
      of medical care, including operative and transcatheter reinterventions,
      noncardiac surgeries, and hospitalizations. Twenty-one subjects with IAA with
      median age of 9 years were studied. Reintervention rates were 38% for left
      ventricular outflow tract, 33% for AA, and 24% for both. Rates of reintervention
      were highest in the first year of life and decreased in subsequent years. Left
      ventricular ejection fraction was preserved (72 +/- 6%). Maximal oxygen
      consumption, maximal work, and forced vital capacity were both significantly
      decreased from age and sex norms (p < 0.0001). Health status and quality of life
      were both severely decreased. Subjects with IAA demonstrate a significant burden
      of operative and transcatheter intervention and large magnitude deficits in
      exercise performance, health status, and health-related quality of life.

PMID- 24036995
TI  - The impact of out-of-pocket costs on the use of intrauterine contraception among
      women with employer-sponsored insurance.
AB  - BACKGROUND: Long-acting reversible contraception (LARC) is highly effective but
      also has higher initiation costs than oral contraceptive methods, which may
      contribute to relatively low use. The Affordable Care Act requires most private
      insurance plans to cover contraceptive services without patient cost-sharing.
      Whether this mandate will increase LARC use is unknown. OBJECTIVE: To assess the
      relationship between cost-sharing and use of LARC among privately insured women.
      DESIGN: Cross-sectional analysis using Truven Health MarketScan data from January
      2011 to December 2011. SUBJECTS: Women aged 14-45 years with continuous insurance
      coverage enrolled in health plan products that covered branded and generic oral
      contraceptive pills (OCPs) and intrauterine devices (IUDs). We selected women
      using OCPs and IUDs as these are the most commonly used short-acting and long
      acting reversible methods, respectively (N=1,682,425). MEASURES: Multivariable
      regression was used to assess the association of the level of out-of-pocket costs
      for IUDs for each patient's plan and IUD initiation, adjusting for out-of-pocket
      costs for branded and generic OCPs and patient characteristics. RESULTS: Overall,
      5.5% of women initiated an IUD in 2011. After adjustment, IUD initiation was less
      likely among women with higher versus lower co-pays (adjusted risk ratio=0.65;
      95% CI, 0.64-0.67). Women who saw an obstetrician/gynecologist during 2011 were
      more likely to initiate an IUD (adjusted risk ratio=2.49; 95% CI, 2.45-2.53).
      CONCLUSIONS: Rates of IUD use are low among privately insured women in the United
      States, and higher cost-sharing is associated with lower rates of IUD use.
      Together with other measures to promote LARC use, eliminating co-pays for
      contraception could promote the use of these more effective and cost-effective
      methods.

PMID- 24036996
TI  - Preventive services for adults: how have differences across subgroups changed
      over the past decade?
AB  - BACKGROUND: A large literature documents cross-sectional differences in adult
      preventive services across population subgroups. Less is known, however, about
      how these differences have changed over time. OBJECTIVES: This study tracks
      changes over time in the distribution of preventive services use across groups
      defined by poverty status, race/ethnicity, insurance coverage, Census region, and
      urbanicity. METHODS: Data from the 1996-2008 Medical Expenditure Panel Survey are
      used to examine 5 preventive services: general checkups, blood pressure
      screening, blood cholesterol screening, Pap smears, and mammograms. Multivariate
      logistic regression models of preventive services use are used to compute
      adjusted utilization for each subgroup of adults aged 19-64 in 1996/1998,
      2002/2003, and 2007/2008. We then examine the extent to which percentage point
      gaps in utilization rates across subgroups have changed between 1996/1998 and
      2007/2008. RESULTS: Our analysis of utilization rates across subgroups and over
      time identified only rare cases in which subgroup differences narrowed or widened
      between 1996/1998 and 2007/2008. Rather, differences across subgroups tended to
      persist over time. Some of the largest (adjusted) gaps are between adults with
      and without coverage, and only for blood cholesterol screening do we observe
      significant narrowing of the gap between the uninsured and the privately insured.
      Regional differences persisted or widened over the study period. CONCLUSIONS: On
      the eve of health reform implementation, a key challenge facing the Affordable
      Care Act will be to address persistent differences in preventive services use
      within the US population.

PMID- 24036997
TI  - Is emergency department crowding associated with increased "bounceback"
      admissions?
AB  - OBJECTIVE: Emergency department (ED) crowding is linked with poor quality of care
      and worse outcomes, including higher mortality. With the growing emphasis on
      hospital performance measures, there is additional concern whether inadequate
      care during crowded periods increases a patient's likelihood of subsequent
      inpatient admission. We sought to determine if ED crowding during the index visit
      was associated with these "bounceback" admissions. METHODS: We used
      comprehensive, nonpublic, statewide ED and inpatient discharge data from the
      California Office of Statewide Health Planning and Development from 2007 to
      identify index outpatient ED visits and bounceback admissions within 7 days. We
      further used ambulance diversion data collected from California local emergency
      medical services agencies to identify crowded days using intrahospital daily
      diversion hour quartiles. Using a hierarchical logistic regression model, we then
      determined if patients visiting on crowded days were more likely to have a
      subsequent bounceback admission. RESULTS: We analyzed 3,368,527 index visits
      across 202 hospitals, of which 596,471 (17.7%) observations were on crowded days.
      We found no association between ED crowding and bounceback admissions. This lack
      of relationship persisted in both a discrete (high/low) model (OR, 1.01; 95% CI,
      0.99, 1.02) and a secondary model using ambulance diversion hours as a continuous
      predictor (OR, 1.00; 95% CI, 1.00, 1.00). CONCLUSIONS: Crowding as measured by
      ambulance diversion does not have an association with hospitalization within 7
      days of an ED visit discharge. Therefore, bounceback admission may be a poor
      measure of delayed or worsened quality of care due to crowding.

PMID- 24036999
TI  - Research on ionic homeostatic equilibrium may change our view about epilepsy.

PMID- 24036998
TI  - Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively
      regulates inflammatory cytokine production in NK cells.
AB  - Inflammation is a critical component of the immune response. However, acute or
      chronic inflammation can be highly destructive. Uncontrolled inflammation forms
      the basis for allergy, asthma and various autoimmune disorders. Here we
      identified a signaling pathway that was exclusively responsible for the
      production of inflammatory cytokines but not for cytotoxicity. Recognition of
      tumor cells expressing the NK cell-activatory ligands H60 or CD137L by mouse
      natural killer (NK) cells led to efficient cytotoxicity and the production of
      inflammatory cytokines. Both of those effector functions required the kinases
      Lck, Fyn and PI(3)K (subunits p85alpha and p110delta) and the signaling protein
      PLC-gamma2. However, a complex of Fyn and the adaptor ADAP exclusively regulated
      the production of inflammatory cytokines but not cytotoxicity in NK cells. That
      unique function of ADAP required a Carma1-Bcl-10-MAP3K7 signaling axis. Our
      results have identified molecules that can be targeted to regulate inflammation
      without compromising NK cell cytotoxicity. 

PMID- 24037000
TI  - Electronic health records: beyond the digitization of medical files.

PMID- 24037001
TI  - Tegumentary manifestations of Noonan and Noonan-related syndromes.
AB  - OBJECTIVES: Noonan and Noonan-related syndromes are common autosomal dominant
      disorders with neuro-cardio-facial-cutaneous and developmental involvement. The
      objective of this article is to describe the most relevant tegumentary findings
      in a cohort of 41 patients with Noonan or Noonan-related syndromes and to detail
      certain aspects of the molecular mechanisms underlying ectodermal involvement.
      METHODS: A standard questionnaire was administered. A focused physical
      examination and a systematic review of clinical records was performed on all
      patients to verify the presence of tegumentary alterations. The molecular
      analysis of this cohort included sequencing of the following genes in all
      patients: PTPN1, SOS1, RAF1, KRAS, SHOC2 and BRAF. RESULTS: The most frequent
      tegumentary alterations were xeroderma (46%), photosensitivity (29%), excessive
      hair loss (24%), recurrent oral ulcers (22%), curly hair (20%), nevi (17%),
      markedly increased palmar and plantar creases (12%), follicular hyperkeratosis
      (12%), palmoplantar hyperkeratosis (10%), cafe-au-lait spots (10%) and sparse
      eyebrows (7%). Patients with mutations in PTPN11 had lower frequencies of palmar
      and plantar creases and palmar/plantar hyperkeratosis compared with the other
      patients. CONCLUSIONS: We observed that patients with mutations in genes directly
      involved in cell proliferation kinase cascades (SOS1, BRAF, KRAS and RAF1) had a
      higher frequency of hyperkeratotic lesions compared with patients with mutations
      in genes that have a more complex interaction with and modulation of cell
      proliferation kinase cascades (PTPN11).

PMID- 24037002
TI  - The level of circulating endothelial progenitor cells may be associated with the
      occurrence and recurrence of chronic subdural hematoma.
AB  - OBJECTIVES: The onset of chronic subdural hematoma may be associated with direct
      or indirect minor injuries to the head or a poorly repaired vascular injury.
      Endothelial progenitor cells happen to be one of the key factors involved in
      hemostasis and vascular repair. This study was designed to observe the levels of
      endothelial progenitor cells, white blood cells, platelets, and other indicators
      in the peripheral blood of patients diagnosed with chronic subdural hematoma to
      determine the possible relationship between the endothelial progenitor cells and
      the occurrence, development, and outcomes of chronic subdural hematoma. METHOD:
      We enrolled 30 patients with diagnosed chronic subdural hematoma by computer
      tomography scanning and operating procedure at Tianjin Medical University General
      Hospital from July 2009 to July 2011. Meanwhile, we collected 30 cases of
      peripheral blood samples from healthy volunteers over the age of 50.
      Approximately 2 ml of blood was taken from veins of the elbow to test the
      peripheral blood routine and coagulation function. The content of endothelial
      progenitor cells in peripheral blood mononuclear cells was determined by flow
      cytometry. RESULTS: The level of endothelial progenitor cells in peripheral blood
      was significantly lower in preoperational patients with chronic subdural
      hematomas than in controls. There were no significant differences between the two
      groups regarding the blood routine and coagulation function. However, the levels
      of circulating endothelial progenitor cells were significantly different between
      the recurrent group and the non-recurrent group. CONCLUSIONS: The level of
      circulating endothelial progenitor cells in chronic subdural hematoma patients
      was significantly lower than the level in healthy controls. Meanwhile, the level
      of endothelial progenitor cells in recurrent patients was significantly lower
      than the level in patients without recurrence. Endothelial progenitor cells may
      be related to the occurrence and recurrence of chronic subdural hematoma.

PMID- 24037003
TI  - One-year treatment follow-up of plantar fasciitis: radial shockwaves vs.
      conventional physiotherapy.
AB  - OBJECTIVE: To compare radial shockwave treatment with conventional physiotherapy
      for plantar fasciitis after 12 months of follow-up. METHOD: This was a
      randomized, prospective, comparative clinical study. Forty patients with a
      diagnosis of plantar fasciitis were divided randomly into two treatment groups:
      group 1, with 20 patients who underwent ten physiotherapy sessions comprising
      ultrasound, kinesiotherapy and guidance for home-based stretching; and group 2,
      with 20 patients who underwent three applications of radial shockwaves, once a
      week, and guidance for home-based stretching. All patients were assessed
      regarding pain and functional abilities before treatment, immediately after and
      12 months after treatment. The mean age was 49.6 +/-11.8 years (range: 25-68
      years), 85% were female, 88% were overweight, 63% were affected bilaterally, and
      83% used analgesics regularly. RESULTS: At the 12-month follow-up, both
      treatments were effective for improving pain and functional ability among the
      patients with plantar fasciitis. The improvement with shockwaves was faster.
      CONCLUSION: Shockwave treatment was not more effective than conventional
      physiotherapy treatment 12 months after the end of the treatment.

PMID- 24037004
TI  - Association of child maltreatment and psychiatric diagnosis in Brazilian children
      and adolescents.
AB  - OBJECTIVES: The objective of this study was to evaluate the association between
      different types of child maltreatment and the presence of psychiatric disorders
      in highly vulnerable children and adolescents served by a multidisciplinary
      program. METHODS: In total, 351 patients with a mean age of 12.47, of whom 68.7%
      were male and 82.1% lived in shelters, underwent psychiatric evaluations based on
      the Kiddie-Sads-Present and Lifetime Version. Two different methods were used to
      evaluate maltreatment: medical records were reviewed to identify previous
      diagnoses related to socioeconomic and psychosocial circumstances, and the
      Childhood Trauma Questionnaire was used to obtain a structured history of trauma.
      Bivariate associations were evaluated between psychiatric disorders and evidence
      of each type and the frequency of abuse. RESULTS: The most frequent psychiatric
      diagnoses were substance use disorders, affective disorders and specific
      disorders of early childhood, whereas 13.67% of the sample had no psychiatric
      diagnosis. All patients suffered neglect, and 58.4% experienced physical or
      sexual abuse. The presence of a history of multiple traumas was only associated
      with a diagnosis of substance use disorder. Mental retardation showed a strong
      positive association with reported physical abuse and emotional neglect. However,
      a negative correlation was found when we analyzed the presence of a history of
      multiple traumas and mental retardation. CONCLUSION: All children living in
      adverse conditions deserve careful assistance, but we found that physical abuse
      and emotional neglect were most strongly associated with mental retardation and
      multiple traumas with substance abuse.

PMID- 24037005
TI  - Infection as an independent risk factor for mortality in the surgical intensive
      care unit.
AB  - OBJECTIVES: Medical and surgical intensive care unit patients represent two
      different populations and require different treatment approaches. The aim of this
      study was to investigate the parameters associated with mortality in medical and
      surgical intensive care units. METHODS: This was a prospective cohort study of
      adult patients admitted to a medical and surgical intensive care unit teaching
      hospital over an 11-month period. Factors associated with mortality were explored
      using logistic regression analysis. RESULTS: In total, 827 admissions were
      observed, and 525 patients >18 years old and with a length of stay >24 h were
      analyzed. Of these patients, 227 were in the medical and 298 were in the surgical
      intensive care unit. The surgical patients were older (p<0.01) and had shorter
      lengths of stay (p<0.01). The mortality in the intensive care unit (35.1 vs.
      26.2, p = 0.02) and hospital (48.8 vs. 35.5, p<0.01) was higher for medical
      patients. For patients in the surgical intensive care unit, death was
      independently associated with the need for mechanical ventilation, prognostic
      score (SAPS II), community-acquired infection, nosocomial infection, and
      intensive care unit-acquired infection. For patients in the medical intensive
      care unit, death was independently associated with the need for mechanical
      ventilation and prognostic score. CONCLUSIONS: Although the presence of infection
      is associated with a high mortality in both the medical and surgical intensive
      care units, the results of this prospective study suggest that infection has a
      greater impact in patients admitted to the surgical intensive care unit. Measures
      and trials to prevent and treat sepsis may be most effective in the surgical
      intensive care unit population.

PMID- 24037006
TI  - Effect of diabetes on mortality and length of hospital stay in patients with
      renal or perinephric abscess.
AB  - OBJECTIVES: We compared the risk of in-hospital mortality and the length of
      hospital stay between diabetic and non-diabetic patients hospitalized for renal
      or perinephric abscess. METHOD: The data analyzed in this study were retrieved
      from Taiwan's National Health Insurance claims. The risk of in-hospital mortality
      and the length of hospital stay were compared between 1,715 diabetic patients,
      hospitalized because of renal or perinephric abscess in Taiwan between 1997 and
      2007, and a random sample of 477 non-diabetes patients with renal or perinephric
      abscess. RESULTS: The in-hospital mortality rates from renal or perinephric
      abscess for the diabetic patients and the non-diabetic patients were not
      different, at 2.3% and 3.4%, respectively. However, diabetes was significantly
      associated with a longer length of hospital stay among patients with renal
      abscess, by 3.38 days (95% confidence interval [CI]: 1.59-5.17). CONCLUSIONS:
      Diabetes does not increase the risk of in-hospital mortality from renal or
      perinephric abscess. Nevertheless, appropriate management of patients with
      diabetes and concurrent renal or perinephric abscess is essential to reduce the
      length of hospital stay.

PMID- 24037007
TI  - Segmented corpus callosum diffusivity correlates with the Expanded Disability
      Status Scale score in the early stages of relapsing-remitting multiple sclerosis.
AB  - OBJECTIVE: The aim of this study was to characterize the microscopic damage to
      the corpus callosum in relapsing-remitting multiple sclerosis (RRMS) with
      diffusion tensor imaging and to investigate the correlation of this damage with
      disability. The diffusion tensor imaging parameters of fractional anisotropy and
      mean diffusivity provide information about the integrity of cell membranes,
      offering two more specific indices, namely the axial and radial diffusivities,
      which are useful for discriminating axon loss from demyelination. METHOD: Brain
      magnetic resonance imaging exams of 30 relapsing-remitting multiple sclerosis
      patients and 30 age- and sex-matched healthy controls were acquired in a 3T
      scanner. The axial diffusivities, radial diffusivities, fractional anisotropy,
      and mean diffusivity of five segments of the corpus callosum, correlated to the
      Expanded Disability Status Scale score, were obtained. RESULTS: All corpus
      callosum segments showed increased radial diffusivities and mean diffusivity, as
      well as decreased fractional anisotropy, in the relapsing-remitting multiple
      sclerosis group. The axial diffusivity was increased in the posterior midbody and
      splenium. The Expanded Disability Status Scale scores correlated more strongly
      with axial diffusivities and mean diffusivity, with an isolated correlation with
      radial diffusivities in the posterior midbody of the corpus callosum. There was
      no significant correlation with lesion loads. CONCLUSION: Neurological
      dysfunction in relapsing-remitting multiple sclerosis can be influenced by
      commissural disconnection, and the diffusion indices of diffusion tensor imaging
      are potential biomarkers of disability that can be assessed during follow-up.

PMID- 24037008
TI  - Changes in body weight, C-reactive protein, and total adiponectin in non-obese
      women after 12 months of a small-volume, home-based exercise program.
AB  - OBJECTIVE: Our objective was to evaluate the effects of small-volume, home-based
      exercise combined with slight caloric restriction on the inflammatory markers C
      reactive protein and adiponectin. METHODS: In total, 54 women were randomly
      assigned to one of two groups for exercise intervention: the control or home
      based exercise groups. Weight, waist and hip circumferences, and inflammatory
      markers were measured at baseline and after 6 and 12 months. Women allocated to
      the home-based exercise group received a booklet explaining the physical
      exercises to be practiced at home at least 3 times per week, 40 minutes per
      session, at low-to-moderate intensity. All participants received dietary
      counseling aimed at reducing caloric intake by 100-300 calories per day, with a
      normal distribution of macro-nutrients (26-28% of energy as fat).
      Clinicaltrials.gov: NCT01206413 RESULTS: The home-based exercise group showed a
      significantly greater reduction in weight and body mass index at six months, but
      no difference between groups was observed thereafter. With regard to the
      inflammatory markers, a greater but non-statistically significant reduction was
      found for C-reactive protein in the home-based exercise group at six months;
      however, this difference disappeared after adjusting for weight change. No
      differences in adiponectin were found at the 6- or 12-month follow-up.
      CONCLUSION: Small-volume, home-based exercise did not promote changes in
      inflammatory markers independent of weight change.

PMID- 24037009
TI  - Colonization pressure as a risk factor for colonization by multiresistant
      Acinetobacter spp and carbapenem-resistant Pseudomonas aeruginosa in an intensive
      care unit.
AB  - OBJECTIVE: To determine factors associated with colonization by carbapenem
      resistant Pseudomonas aeruginosa and multiresistant Acinetobacter spp. METHODS:
      Surveillance cultures were collected from patients admitted to the intensive care
      unit at admission, on the third day after admission and weekly until discharge.
      The outcome was colonization by these pathogens. Two interventions were
      implemented: education and the introduction of alcohol rubs. Compliance with hand
      hygiene, colonization pressure, colonization at admission and risk factors for
      colonization were evaluated. RESULTS: The probability of becoming colonized
      increased during the study. The incidence density of colonization by carbapenem
      resistant P. aeruginosa and multiresistant Acinetobacter spp. and colonization
      pressure were different between periods, increasing gradually throughout the
      study. The increase in colonization pressure was due to patients already
      colonized at admission. The APACHE II score, colonization pressure in the week
      before the outcome and male gender were independent risk factors for
      colonization. Every 1% increase in colonization pressure led to a 2% increase in
      the risk of being colonized. CONCLUSION: Colonization pressure is a risk factor
      for carbapenem-resistant P. aeruginosa and multiresistant Acinetobacter spp.
      colonization. When this pressure reaches critical levels, efforts primarily aimed
      at hand hygiene may not be sufficient to prevent transmission.

PMID- 24037010
TI  - Decreased levels of alpha-1-acid glycoprotein are related to the mortality of
      septic patients in the emergency department.
AB  - OBJECTIVE: To determine the validity of alpha-1-acid glycoprotein as a novel
      biomarker for mortality in patients with severe sepsis. METHODS: We prospectively
      included patients with severe sepsis or septic shock at the emergency department
      at a single tertiary referral teaching hospital. All of the patients were
      enrolled within the first 24 hours of emergency department admission, and
      clinical data and blood samples were obtained. As the primary outcome, we
      investigated the association of serum levels of alpha-1-acid glycoprotein and 96
      hour mortality with logistic regression analysis and generalized estimating
      equations adjusted for age, sex, shock status and Acute Physiology and Chronic
      Health Evaluation II score. RESULTS: Patients with septic shock had lower alpha-1
      acid glycoprotein levels at the time of emergency department admission compared
      to patients without shock (respectively, 149.1 +/-42.7 vs. 189.8 +/-68.6; p =
      0.005). Similarly, non-survivors in the first 96 hours were also characterized by
      lower levels of alpha-1-acid glycoprotein at the time of emergency department
      admission compared to survivors (respectively, 132.18 +/-50.2 vs. 179.8 +/-61.4;
      p = 0.01). In an adjusted analysis, alpha-1-acid glycoprotein levels <=120 mg/dL
      were significantly associated with 96-hour mortality (odds ratio = 14.37; 95%
      confidence interval = 1.58 to 130.21). CONCLUSION: Septic shock patients
      exhibited lower circulating alpha-1-acid glycoprotein levels than patients
      without shock. Alpha-1-acid glycoprotein levels were independently associated
      with 96-hour mortality in individuals with severe sepsis.

PMID- 24037011
TI  - Prevalence of dementia subtypes in a developing country: a clinicopathological
      study.
AB  - OBJECTIVES: To assess the distribution of dementia subtypes in Brazil using a
      population-based clinicopathological study. METHOD: Brains from deceased
      individuals aged >=50 years old were collected after the next of kin signed an
      informed consent form and provided information through standardized
      questionnaires. Post-mortem clinical diagnoses were established in consensus
      meetings, and only cases with moderate or severe dementia or without cognitive
      impairment were included in the analysis. Immunohistochemical neuropathological
      examinations were performed following the universally accepted guidelines. A
      diagnosis of Alzheimer's disease was made when there were at least both a
      moderate density of neuritic plaques (Consortium to Establish a Register for
      Alzheimer's disease B or C) and Braak stage III for neurofibrillary tangle
      distribution. For the diagnosis of vascular dementia, at least three zones or
      strategic areas had to be affected by infarcts, lacunae, or microinfarcts.
      RESULTS: From 1,291 subjects, 113 cases were classified as having moderate or
      severe dementia, and 972 cases were free of cognitive impairment. The
      neuropathological diagnoses of the dementia sub-group were Alzheimer's disease
      (35.4%), vascular dementia (21.2%), Alzheimer's disease plus vascular dementia
      (13.3%), and other causes of dementia (30.1%). Small-vessel disease, which alone
      was not considered sufficient for a vascular dementia diagnosis, was present in
      38.9% of all of the dementia cases and in 16.8% of the group without cognitive
      impairment (odds ratio = 2.91; 95% confidence interval, 1.53-5.51), adjusted for
      age, sex, and education. CONCLUSIONS: The relatively high frequencies of vascular
      dementia and small-vessel disease in the dementia sub-group constitute relevant
      findings for public health initiatives because control of vascular risk factors
      could decrease the prevalence of dementia in developing countries.

PMID- 24037012
TI  - Effects of terlipressin and naloxone compared with epinephrine in a rat model of
      asphyxia-induced cardiac arrest.
AB  - OBJECTIVE: To evaluate the hemodynamic and metabolic effects of terlipressin and
      naloxone in cardiac arrest. METHODS: Cardiac arrest in rats was induced by
      asphyxia and maintained for 3.5 minutes. Animals were then resuscitated and
      randomized into one of six groups: placebo (n = 7), epinephrine (0.02 mg/kg; n =
      7), naloxone (1 mg/kg; n = 7) or terlipressin, of which three different doses
      were tested: 50 ug/kg (TP50; n = 7), 100 ug/kg (TP100; n = 7) and 150 ug/kg
      (TP150; n = 7). Hemodynamic variables were measured at baseline and at 10 (T10),
      20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes after cardiac arrest. Arterial
      blood samples were collected at T10, T30 and T60. RESULTS: The mean arterial
      pressure values in the TP50 group were higher than those in the epinephrine group
      at T10 (165 vs. 112 mmHg), T20 (160 vs. 82 mmHg), T30 (143 vs. 66 mmHg), T45 (119
      vs. 67 mmHg) and T60 (96 vs. 66.8 mmHg). The blood lactate level was lower in the
      naloxone group than in the epinephrine group at T10 (5.15 vs. 10.5 mmol/L), T30
      (2.57 vs. 5.24 mmol/L) and T60 (2.1 vs. 4.1 mmol/L). CONCLUSIONS: In this rat
      model of asphyxia-induced cardiac arrest, terlipressin and naloxone were
      effective vasopressors in cardiopulmonary resuscitation and presented better
      metabolic profiles than epinephrine. Terlipressin provided better hemodynamic
      stability than epinephrine.

PMID- 24037013
TI  - A simplified experimental model of large-for-size liver transplantation in pigs.
AB  - OBJECTIVE: The ideal ratio between liver graft mass and recipient body weight for
      liver transplantation in small infants is unknown; however, if this ratio is over
      4%, a condition called large-for-size may occur. Experimental models of large-for
      size liver transplants have not been described in the literature. In addition,
      orthotopic liver transplantation is marked by high morbidity and mortality rates
      in animals due to the clamping of the venous splanchnic system. Therefore, the
      objective of this study was to create a porcine model of large-for-size liver
      transplantation with clamping of the supraceliac aorta during the anhepatic phase
      as an alternative to venovenous bypass. METHOD: Fourteen pigs underwent liver
      transplantation with whole-liver grafts without venovenous bypass and were
      divided into two experimental groups: the control group, in which the weights of
      the donors were similar to the weights of the recipients; and the large-for-size
      group, in which the weights of the donors were nearly 2 times the weights of the
      recipients. Hemodynamic data, the results of serum biochemical analyses and
      histological examination of the transplanted livers were collected. RESULTS: The
      mortality rate in both groups was 16.5% (1/7). The animals in the large-for-size
      group had increased serum levels of potassium, sodium, aspartate aminotransferase
      and alanine aminotransferase after graft reperfusion. The histological analyses
      revealed that there were no significant differences between the groups.
      CONCLUSION: This transplant method is a feasible experimental model of large-for
      size liver transplantation.

PMID- 24037014
TI  - A systematic review of the effects of different types of therapeutic exercise on
      physiologic and functional measurements in patients with HIV/AIDS.
AB  - Several studies have reported the benefits of exercise training for adults with
      HIV, although there is no consensus regarding the most efficient modalities. The
      aim of this study was to determine the effects of different types of exercise on
      physiologic and functional measurements in patients with HIV using a systematic
      strategy for searching randomized controlled trials. The sources used in this
      review were the Cochrane Library, EMBASE, MEDLINE, and PEDro from 1950 to August
      2012. We selected randomized controlled trials examining the effects of exercise
      on body composition, muscle strength, aerobic capacity, and/or quality of life in
      adults with HIV. Two independent reviewers screened the abstracts using the
      Cochrane Collaboration's protocol. The PEDro score was used to evaluate
      methodological quality. In total, 29 studies fulfilled the inclusion criteria.
      Individual studies suggested that exercise training contributed to improvement of
      physiologic and functional parameters, but that the gains were specific to the
      type of exercise performed. Resistance exercise training improved outcomes
      related to body composition and muscle strength, with little impact on quality of
      life. Aerobic exercise training improved body composition and aerobic capacity.
      Concurrent training produced significant gains in all outcomes evaluated,
      although moderate intensity and a long duration were necessary. We concluded that
      exercise training was shown to be a safe and beneficial intervention in the
      treatment of patients with HIV. 

PMID- 24037016
TI  - Modified Hodge test as screening test for spreading carbapenemase resistance has
      become more important.

PMID- 24037015
TI  - Comparison of the effects of continuous positive airway pressure, oral appliance
      and exercise training in obstructive sleep apnea syndrome.
AB  - OBJECTIVE: There are several treatments for obstructive sleep apnea syndrome,
      such as weight loss, use of an oral appliance and continuous positive airway
      pressure, that can be used to reduce the signs and symptoms of obstructive sleep
      apnea syndrome. Few studies have evaluated the effectiveness of a physical
      training program compared with other treatments. The aim of this study was to
      assess the effects of physical exercise on subjective and objective sleep
      parameters, quality of life and mood in obstructive sleep apnea patients and to
      compare these effects with the effects of continuous positive airway pressure and
      oral appliance treatments. METHODS: Male patients with moderate to severe
      obstructive sleep apnea and body mass indices less than 30 kg/m2 were randomly
      assigned to three groups: continuous positive airway pressure (n = 9), oral
      appliance (n = 9) and physical exercise (n = 7). Polysomnographic recordings,
      blood samples and daytime sleepiness measurements were obtained prior to and
      after two months of physical exercise or treatment with continuous positive
      airway pressure or an oral appliance. Clinicaltrials.gov: NCT01289392 RESULTS:
      After treatment with continuous positive airway pressure or an oral appliance,
      the patients presented with a significant reduction in the apnea-hypopnea index.
      We did not observe changes in the sleep parameters studied in the physical
      exercise group. However, this group presented reductions in the following
      parameters: T leukocytes, very-low-density lipoprotein and triglycerides. Two
      months of exercise training also had a positive impact on subjective daytime
      sleepiness. CONCLUSIONS: Our results suggest that isolated physical exercise
      training was able to modify only subjective daytime sleepiness and some blood
      measures. Continuous positive airway pressure and oral appliances modified the
      apnea-hypopnea index.

PMID- 24037019
TI  - Erythematous protruding skin lesion in the retroauricular area. Angiolymphoid
      hyperplasia with eosinophilia.

PMID- 24037018
TI  - Fine mapping quantitative resistances to downy mildew in lettuce revealed
      multiple sub-QTLs with plant stage dependent effects reducing or even promoting
      the infection.
AB  - KEY MESSAGE: Three regions with quantitative resistance to downy mildew of non
      host and wild lettuce species, Lactuca saligna , disintegrate into seventeen sub
      QTLs with plant-stage-dependent effects, reducing or even promoting the
      infection. Previous studies on the genetic dissection of the complete resistance
      of wild lettuce, Lactuca saligna, to downy mildew revealed 15 introgression
      regions that conferred plant stage dependent quantitative resistances (QTLs).
      Three backcross inbred lines (BILs), carrying an individual 30-50 cM long
      introgression segment from L. saligna in a cultivated lettuce, L. sativa,
      background, reduced infection by 60-70 % at young plant stage and by 30-50 % at
      adult plant stage in field situations. We studied these three quantitative
      resistances in order to narrow down their mapping interval and determine their
      number of loci, either single or multiple. We performed recombinant screenings
      and developed near isogenic lines (NILs) with smaller overlapping L. saligna
      introgressions (substitution mapping). In segregating introgression line
      populations, recombination was suppressed up to 17-fold compared to the original
      L. saligna * L. sativa F 2 population. Recombination suppression depended on the
      chromosome region and was stronger suppressed at the smallest introgression
      lengths. Disease evaluation of the NILs revealed that the resistance of all three
      BILs was not explained by a single locus but by multiple sub-QTLs. The 17 L.
      saligna-derived sub-QTLs had a smaller and plant stage dependent resistance
      effect, some segments reducing; others even promoting downy mildew infection.
      Implications for lettuce breeding are outlined.

PMID- 24037020
TI  - Plasmonic engineering of spontaneous emission from silicon nanocrystals.
AB  - Silicon nanocrystals offer huge advantages compared to other semi-conductor
      quantum dots as they are made from an abundant, non-toxic material and are
      compatible with silicon devices. Besides, among a wealth of extraordinary
      properties ranging from catalysis to nanomedicine, metal nanoparticles are known
      to increase the radiative emission rate of semiconductor quantum dots. Here, we
      use gold nanoparticles to accelerate the emission of silicon nanocrystals. The
      resulting integrated hybrid emitter is 5-fold brighter than bare silicon
      nanocrystals. We also propose an in-depth analysis highlighting the role of the
      different physical parameters in the photoluminescence enhancement phenomenon.
      This result has important implications for the practical use of silicon
      nanocrystals in optoelectronic devices, for instance for the design of efficient
      down-shifting devices that could be integrated within future silicon solar cells.

PMID- 24037021
TI  - Etoposide-containing conditioning regimen reduces the occurrence of
      hemophagocytic lymphohistiocytosis after SCT.
AB  - Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of
      severe hyperinflammation caused by uncontrolled proliferation of activated
      lymphocytes and macrophages that secrete high amounts of inflammatory cytokines.
      HLH occurring after SCT is difficult to diagnose. It is characterized by severe
      clinical manifestations and high mortality. Despite current therapeutic
      approaches, outcomes remain poor. We analyzed the incidence and risk factors of
      HLH after SCT and the response to treatment and prognosis of 554 patients with
      HLH after SCT. The cumulative incidence of HLH after SCT was 4.3% (24/554). Use
      of etoposide in the conditioning regimen was only factor that reduced HLH after
      SCT (P=0.027). All patients who received autologous transplantation were
      successfully treated. Patients with liver dysfunction (for example, high total
      bilirubin level, prolonged prothrombin time and high level of fibrinogen
      degradation products) had a poor response to treatment for HLH. Physicians should
      be cautious of HLH, while not using etoposide for conditioning regimen. 

PMID- 24037022
TI  - Effective prevention of GVHD using in vivo T-cell depletion with anti-lymphocyte
      globulin in HLA-identical or -mismatched sibling peripheral blood stem cell
      transplantation.
AB  - To investigate the impact of anti-lymphocyte globulin (ATG-Fresenius) as part of
      the HLA-sibling transplantation, we evaluated 238 patients (median age 48 years)
      with different diagnoses (AML, ALL, CML and lymphoproliferative disorders). A
      total of 79 patients received ATG and 159 patients did not. In the ATG group,
      there were more HLA-mismatched donors (6% vs 1%, p=0.02), bad risk patients (70%
      vs 55%, P=0.04), reduced intensity conditioning (RIC) regimens (65% vs 34%,
      P=<0.001) and older patients (median age 51 vs 48 years, P=0.002). The median
      time to leukocyte engraftment was significantly faster in the non-ATG group (13
      vs 15 days, P < 0.001). EBV reactivation was more often seen in the ATG group (9%
      vs 2%, P=0.05). Cumulative incidence of acute and chronic GVHD was less observed
      in the ATG group (27% vs 40%, P=0.004, and 33% vs 54%, P=0.002). The cumulative
      incidence rates of non-relapse mortality and of relapse at 5 years were 20 and
      34%, respectively, for ATG and 34 and 29%, respectively, for non-ATG (P=0.06 and
      P=0.3). ATG can prevent GVHD without an obvious risk of relapse but should be
      confirmed in a randomized study. 

PMID- 24037023
TI  - The impact of T-cell depletion techniques on the outcome after haploidentical
      hematopoietic SCT.
AB  - Several T-cell depletion (TCD) techniques are used for haploidentical
      hematopoietic SCT (HSCT), but direct comparisons are rare. We therefore studied
      the effect of in vitro TCD with graft engineering (CD34 selection or CD3/CD19
      depletion, 74%) or in vivo TCD using alemtuzumab (26%) on outcome, immune
      reconstitution and infections after haploidentical HSCT. We performed a
      retrospective multicenter analysis of 72 haploidentical HSCT in Switzerland.
      Sixty-seven patients (93%) had neutrophil engraftment. The 1-year OS, TRM and
      relapse incidence were 48 (36-60)%, 20 (11-33)% and 42 (31-57)%, respectively,
      without differences among the TCD groups. In vivo TCD caused more profound
      lymphocyte suppression early after HSCT, whereas immune recovery beyond the
      second month was comparable between the two groups. Despite anti-infective
      prophylaxis, most patients experienced post-transplant infectious complications
      (94%). Patients with in vivo TCD had a higher incidence of CMV reactivations (54%
      vs 28%, P=0.015), but this did not result in a higher TRM. In conclusion, TCD by
      graft engineering or alemtuzumab are equally effective for haploidentical HSCT. 

PMID- 24037024
TI  - Higher therapeutic CsA levels early post transplantation reduce risk of acute
      GVHD and improves survival.
AB  - We studied whether early CsA trough levels were associated with the risk of acute
      GVHD in 337 patients after either sibling PBSC or double umbilical cord blood
      transplantation. All patients, regardless of donor type, started CsA at a dose of
      5 mg/kg i.v. divided twice daily, targeting trough concentrations 200-400 ng/mL.
      The CsA level was studied by a weighted average method calculated by giving 70%
      of the weight to the level that was measured just before the onset of the event
      or day +30. We found that higher weighted average CsA trough levels early post
      transplantation contributed to lower risk of acute GVHD, and lower non-relapse
      and overall mortality. Thus, our data support close monitoring with active
      adjustments of CsA dosing to maintain therapeutic CsA levels in the first weeks
      of allo-HCT. In patients who are near or even modestly above the CsA target
      trough level, in the absence of CsA-related toxicity, dose reduction should be
      cautious to avoid subtherapeutic drug levels resulting in higher risk of acute
      GVHD. 

PMID- 24037025
TI  - Groups: knowledge spreadsheets for symbolic biocomputing.
AB  - Knowledge spreadsheets (KSs) are a visual tool for interactive data analysis and
      exploration. They differ from traditional spreadsheets in that rather than being
      oriented toward numeric data, they work with symbolic knowledge representation
      structures and provide operations that take into account the semantics of the
      application domain. 'Groups' is an implementation of KSs within the Pathway Tools
      system. Groups allows Pathway Tools users to define a group of objects (e.g.
      groups of genes or metabolites) from a Pathway/Genome Database. Groups can be
      transformed (e.g. by transforming a metabolite group to the group of pathways in
      which those metabolites are substrates); combined through set operations;
      analysed (e.g. through enrichment analysis); and visualized (e.g. by painting
      onto a metabolic map diagram). Users of the Pathway Tools-based BioCyc.org
      website have made extensive use of Groups, and an informal survey of Groups users
      suggests that Groups has achieved the goal of allowing biologists themselves to
      perform some data manipulations that previously would have required the
      assistance of a programmer. Database URL: BioCyc.org. 

PMID- 24037026
TI  - Coiled-coil peptide motifs as thermoresponsive valves for mesoporous silica
      nanoparticles.
AB  - Coiled-coil peptide motifs were used as thermo-responsive valves for mesoporous
      silica nanoparticles (MSNs). The controlled release of a model drug as a function
      of temperature was demonstrated. 

PMID- 24037027
TI  - The development of genetic counseling services and training program in Saudi
      Arabia.
AB  - In 2005 the first Saudi genetic counseling training program was established by
      the Department of Medical Genetics at King Faisal Specialist Hospital and
      Research Center (KFSH&RC) in the Kingdom of Saudi Arabia. The program has
      graduated five genetic counselors with high diploma-level degree. This brief
      report describes the development of the genetic counseling training program and
      the factors that led to its establishment. Special emphasis is made to unique
      cultural practices including consanguinity, religious influence, and termination
      of pregnancy. This report also describes the current status of the genetic
      counseling services offered by KFSH&RC and availability of genetic testing. 

PMID- 24037028
TI  - International genetic counseling students' perspective on their training
      experience in the United States.
AB  - International students face social, psychological and academic challenges upon
      moving to a foreign country to pursue higher education. Clinical disciplines such
      as genetic counseling present additional challenges adapting to an unfamiliar
      health care system and different interactions and expectations with patients and
      colleagues. This study used semi-structured interviews to identify challenges
      that international genetic counseling students face during training in the United
      States. Eight international genetic counseling alumni who graduated from U.S.
      accredited programs were interviewed. Participants stated that the U.S. academic
      system was unfamiliar-class participation and paper-writing required the greatest
      adjustment. There was a need for help in understanding social norms in academic
      settings. Clinically, they were unfamiliar with the dynamics and communication
      style of U.S. families. Non-native English speakers experienced greater
      difficulty in all areas. Most participants reported that they were uncomfortable
      asking for help in transitioning to life, study and work. Participants identified
      mentorship programs for international students as potentially useful in
      clarifying expectations in academic and clinical settings. These results may
      assist international students preparing to study genetic counseling in the U.S.
      and may help genetic counseling training programs identify the academic and
      clinical challenges faced by international students. 

PMID- 24037030
TI  - A qualitative study of healthcare providers' perspectives on the implications of
      genome-wide testing in pediatric clinical practice.
AB  - The utilization of genome-wide chromosomal microarray analysis (CMA) in pediatric
      clinical practice provides an opportunity to consider how genetic diagnostics is
      evolving, and to prepare for the clinical integration of genome-wide sequencing
      technologies. We conducted semi-structured interviews with 15 healthcare
      providers (7 genetic counselors, 4 medical geneticists, and 4 non-genetics
      providers) to investigate the impact of CMA on clinical practice, and
      implications for providers, patients and families. Interviews were analyzed
      qualitatively using content analysis. Most providers reported that genomic
      testing enhanced their professional experience and was beneficial to patients,
      primarily due to the improved diagnostic rate compared with earlier chromosomal
      studies. Other effects on practice included moving towards genotype-first
      diagnosis and broadening indications for chromosomal testing. Opinions varied
      concerning informed consent and disclosure of results. The duty to disclose
      incidental findings (IFs) was noted; however concerns were raised about potential
      psychosocial harms of disclosing pre-symptomatic findings. Tensions were revealed
      between the need for comprehensive informed consent for all families and the
      challenges of communicating time-consuming and potentially anxiety-provoking
      information regarding uncertain and incidental findings that may be relevant only
      in rare cases. Genetic counselors can play an important role in liaising with
      families, health professionals and testing laboratories, providing education and
      guidance to non-genetics providers, and enabling families to receive adequate pre
      and post-test information and follow-up care. 

PMID- 24037031
TI  - Identifying outcomes of clinical genetic services: qualitative evidence and
      methodological considerations.
AB  - Extensive research into the tangible and intangible implications of Clinical
      Genetic Services (CGSs) has confirmed the relevance of a multidimensional outcome
      of benefit conceptually linked to perceived control. This paper aims to report
      qualitative findings from one small study aiming to add to the evidence pool
      confirming the relevance of such an outcome to participants from one UK clinical
      genetics center. Data were collected using focus groups and individual interviews
      with 22 service users from the following conditions: Hereditary Breast and
      Ovarian Cancer (HBOC), von Hippel Lindau disorder (VHL), Duchenne and Becker
      muscular dystrophy (DBMD), cystic fibrosis (CF) and tuberous sclerosis (TS).
      Transcripts were analyzed using thematic analysis and four dimensions of benefit
      were identified relating to cognitive, behavioral, social and emotional
      consequences. These dimensions related to an overarching conceptual outcome
      described as Perceived Familial Control. Findings are discussed to illustrate the
      inter-generational and intra-generational familial dimensions of CGSs and
      reinforce the significance of a familial focus to any genetics-specific outcome
      measure. The prospect and methodological considerations of a familial composite
      outcome measure for measuring overall benefit of CGSs is discussed based on
      current and past findings. 

PMID- 24037032
TI  - Protein disulfide isomerase P5-immunopositive inclusions in patients with
      Alzheimer's disease.
AB  - Amyloid plaques and neurofibrillary tangles (NFTs) are the major pathological
      characteristics of Alzheimer's disease (AD). NFTs are composed of tubular
      filaments and paired helical filaments containing polymerized hyperphosphorylated
      tau protein. Another feature of AD is excessive generation of nitric oxide (NO).
      Protein disulfide isomerase (PDI) is a chaperon protein located in the
      endoplasmic reticulum (ER). It was recently reported that NO-induced S
      nitrosylation of PDI inhibits its enzymatic activity, leading to the accumulation
      of polyubiquitinated proteins, and activates the unfolded protein response. In
      addition, we previously reported the presence of PDI-immunopositive NFTs in AD.
      Here, we found that protein disulfide isomerase P5 (P5), which is a member of the
      PDI protein family, was co-localized with tau in NFTs. To our knowledge, this is
      the first report of P5-immunopositive inclusion in AD. Furthermore, we showed
      that S-nitrosylated P5 was present and the expression level of P5 was decreased
      in AD brains compared with that of control brains. We also demonstrated that the
      knock-down of PDI or P5 by siRNA could affect the viability of SH-SY5Y cells
      under ER stress. Previously, the observation of S-nitrosylated PDI in AD was
      reported. NO may inhibit P5 by inducing S-nitrosylation in the same manner as
      PDI, which inhibits its enzymatic activity allowing protein misfolding to occur
      in AD. The accumulation of misfolded proteins induces ER stress and may cause
      apoptosis of neuronal cells through S-nitrosylation and down-regulation of PDI
      and P5 in AD.

PMID- 24037033
TI  - A brief history of voxel-based grey matter analysis in Alzheimer's disease.
AB  - Voxel-based morphometry (VBM) and cortical thickness measurement are common
      techniques to identify regional atrophy in neurodegenerative diseases such as
      Alzheimer's disease (AD). Because studies employing these methods draw
      conclusions regarding patterns of regional cortical degeneration, it is important
      to be aware of their possible limitations. To evaluate the effect of different
      VBM versions, we performed voxel-based analyses through successive versions-from
      SPM99 to SPM8-as well as FSL-VBM on n = 20 AD patients and n = 20 controls.
      Reproducibility was assessed in an independent sample, again of n = 20 per group,
      from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Further, we
      tested the hypothesis that VBM can sensitively detect hippocampal atrophy, but is
      relatively insensitive to changes in the cortical ribbon, by contrasting VBM with
      FreeSurfer cortical thickness measurements. The results with both datasets
      confirmed that VBM preferentially identifies grey matter lesions in the mesial
      temporal lobe but is largely insensitive to isocortical atrophy. In contrast,
      FreeSurfer identified thinning of cortical ribbon association cortex more
      significant in post- rather than pre-Rolandic areas and with relative
      preservation of primary sensory-motor regions-in other words precisely as would
      be expected in AD. The results highlight a bias that VBM has toward detecting
      mesial temporal lobe atrophy. This finding has important implications for
      interpretation of clinical and cognitive studies in AD.

PMID- 24037034
TI  - Trends in diet and Alzheimer's disease during the nutrition transition in Japan
      and developing countries.
AB  - BACKGROUND: Alzheimer's disease (AD) rates in Japan and developing countries have
      risen rapidly in recent years. Researchers have associated factors such as the
      Western diet, obesity, alcohol consumption, and smoking with risk of AD.
      OBJECTIVE: This paper evaluates whether the dietary transition might explain the
      rising trend of AD prevalence in Japan and in developing countries, evaluating
      other factors when possible. METHODS: This study used two approaches to see
      whether dietary or other changes could explain AD trends in Japan and developing
      countries. One approach involved comparing trends of AD in Japan with changes in
      national dietary supply factors, alcohol consumption, and lung cancer mortality
      rates from zero to 25 years before the prevalence data. The second compared AD
      prevalence values for eight developing countries with dietary supply factors from
      zero to 25 years before the prevalence data. RESULTS: For Japan, alcohol
      consumption, animal product, meat and rice supply, and lung cancer rates
      correlated highly with AD prevalence data, with the strongest correlation for a
      lag of 15-25 years. In the eight-country study, total energy and animal fat
      correlated highly with AD prevalence data, with a lag of 15-20 years. Mechanisms
      to explain the findings include increased obesity for the eight countries, and
      increases in cholesterol, saturated fat, and iron from increases in animal
      products and meat supply for Japan. CONCLUSION: Evidently AD rates will continue
      rising in non-Western countries for some time unless we address major risk
      factors involving diet, obesity, and smoking.

PMID- 24037036
TI  - Long-term clinical effect of adjunctive antimicrobial photodynamic therapy in
      periodontal treatment: a randomized clinical trial.
AB  - Mechanical removal of microbial biofilm dental plaque from tooth surfaces is
      important for treatment of periodontal diseases. However, the effectiveness of
      conventional scaling and root planing (SRP) is affected by the local conditions
      and residual bacteria which may affect the healing process. We performed a
      randomized clinical trial to test our hypothesis that adjunctive antimicrobial
      photodynamic therapy (aPDT) plus SRP has significant effect compared with SRP
      alone, which can last for 1 year. The study included 136 sites in 16 patients
      with previously untreated chronic periodontitis, at least one premolar and one
      molar in every quadrant (minimum, four teeth/quadrant) and at least one tooth
      with attachment loss of >=4 mm in every quadrant. In all patients, two randomly
      assigned quadrants were treated with SRP and the other two were treated with SRP
      + aPDT. The clinical parameters of probing pocket depth (PPD), bleeding on
      probing (BOP), and clinical attachment level (CAL) were evaluated at baseline and
      after 3, 6, and 12 months. There were no significant differences between the two
      groups at baseline. PPD and BOP showed significant reduction, and CAL showed
      significant gain from baseline for all three time points in both groups. In
      addition, there were significantly greater reduction and gain for SRP + aPDT than
      for SRP at all three time points. No adverse effects of aPDT were observed. These
      data demonstrate significant improvement in all evaluated clinical parameters for
      at least 1 year and suggest that aPDT as an adjunctive therapy to SRP represents
      a promising therapeutic concept for persistent periodontitis. 

PMID- 24037035
TI  - Cerebral microvascular rather than parenchymal amyloid-beta protein pathology
      promotes early cognitive impairment in transgenic mice.
AB  - Alzheimer's disease (AD) is an age-dependent neurodegenerative condition that
      causes a progressive decline in cognitive function. Accumulation of amyloid beta
      protein (Abeta) in the brain is a prominent feature of AD and related disorders.
      However, the levels of Abeta accumulation alone are not a reliable predictor of
      cognitive deficits. Abeta accumulates in AD brain in the form of parenchymal
      amyloid plaques and cerebral vascular deposits. Although both types of lesions
      can contribute to cognitive decline, their temporal impact remains unclear.
      Moreover, cerebral microvascular pathology is identified as an early driver of
      cognitive impairment. Here for the first time, we compared two transgenic mouse
      strains, Tg-5xFAD and Tg-SwDI, which exhibit similar onset and anatomical
      accumulation of Abeta, but with distinct parenchymal and microvascular
      compartmental deposition, respectively, to assess their impact on cognitive
      impairment. Cohorts of each line were tested at 3 and 6 months of age to assess
      the relationship between spatial working memory performance and quantitative
      pathology. At 3 months of age, Tg-SwDI mice with onset of cerebral microvascular
      amyloid were behaviorally impaired, while the Tg-5xFAD, which had
      disproportionately higher levels of total Abeta, soluble oligomeric Abeta, and
      parenchymal amyloid were not. However, at 6 months of age, behavioral deficits
      for both groups of transgenic mice were evident, as the levels of Abeta
      pathologies in the Tg-5xFAD accumulated to extremely high amounts. The present
      findings suggest early-onset cerebral microvascular amyloid deposition, that
      precedes high parenchymal levels of Abeta, may be an important early factor in
      the development of cognitive deficits.

PMID- 24037037
TI  - Effect of Er:YAG and Nd:YAG lasers on the mineral content of root canal dentin.
AB  - The aim of this study was to assess the effect of two different laser systems on
      the mineral content of root canal dentin. Thirty-six single canal-extracted
      mandibular premolars were used in this study. The teeth were randomly divided
      into two groups of 18 teeth each and prepared with a master apical file #50.
      Dentin chips were obtained by Gates-Glidden burs and saved in Eppendorf tubes to
      serve as a control. Then, root canals were treated with a erbium:yttrium-aluminum
      garnet or neodymium:yttrium-aluminum-garnet laser. Dentin chips were again
      obtained using Gates-Glidden. The levels of calcium (Ca), phosphorus (P),
      magnesium (Mg), sodium (Na), and potassium (K) in each specimen were measured by
      inductively coupled plasma-atomic emission spectrometry. Data were statistically
      analyzed by a Mann-Whitney U test. The changes in Ca, P, Mg, Ca, and K levels and
      the Ca/P ratio after laser irradiations were minimal and statistically not
      significant (p > 0.05). It was determined that the laser systems used in this
      study did not affect the mineral content of root canal dentin. 

PMID- 24037038
TI  - Influence of photoperiods on the growth rate and biomass productivity of green
      microalgae.
AB  - The effect of different photoperiods: 24 h illumination and a 12:12-h light/dark
      (12L:12D) cycle on the growth rate and biomass productivity was studied in five
      algal species: Neochloris conjuncta, Neochloris terrestris, Neochloris texensis,
      Botryococcus braunii and Scenedesmus obliquus. The green microalgae examined
      differ in the reproduction mode. Continuous illumination stimulated the growth of
      B. braunii and S. obliquus more effectively than the growth of the microalgal
      species from the genus Neochloris. However, under shorter duration of light of
      the same intensity (12L:12D cycle), the growth of all the three species of
      Neochloris was stimulated. Under continuous illumination, the specific growth
      rate in the first phase of B. braunii and S. obliquus cultures was higher than
      the growth rate of Neochloris, whereas under the 12L:12D cycle, the specific
      growth rate of all the three Neochloris species was generally higher than that in
      B. braunii and S. obliquus. As a result, the light regime influenced algal
      biomass productivity differently. The maximum biomass productivity was obtained
      in B. braunii and S. obliquus cultures carried out at continuous illumination.
      All the Neochloris species produced biomass more efficiently at the 12L:12D
      cycle, which was two-threefold higher than that of B. braunii and S. obliquus.
      The unicellular species of the green microalgae from the genus Neochloris,
      examined for the first time in this study, are promising prospective objects for
      algal biotechnology. 

PMID- 24037039
TI  - Biosynthesis of sucrose-6-acetate catalyzed by surfactant-coated Candida rugosa
      lipase immobilized on sol-gel supports.
AB  - Sucrose-6-acetate is an important intermediate in the preparation of sucralose (a
      finest sweetener). In our study, Candida rugosa lipase coated with surfactant was
      firstly immobilized on sol-gel supports. Then, the immobilized enzyme was used in
      the regioselective synthesis of sucrose-6-acetate by transesterification of
      sucrose and vinyl acetate. The screening results revealed that Tween 80 was an
      ideal surfactant to coat lipase immobilized in sol-gel and exhibited the highest
      yield of sucrose-6-acetate. Other factors that influenced the yield during the
      preparation process were also studied. Under optimal conditions, the yield of
      sucrose-6-acetate could reach up to 78.68 %, while free lipase was easily
      inactivated in polar solvent. Thermal and operational stabilities were also
      improved significantly. Surfactant-coated lipase immobilized in sol-gel remained
      stable when the temperature was higher than 60  degrees C. Moreover, they could
      maintain high catalytic activity after six recycles. This strategy is economical,
      convenient and promising for the food industry. 

PMID- 24037040
TI  - High-level extracellular production of D-Psicose-3-epimerase with recombinant
      Escherichia coli by a two-stage glycerol feeding approach.
AB  - The aim of this study is to achieve high-level extracellular production of D
      Psicose-3-epimerase (DPE) with recombinant Escherichia coli. High-level
      production of DPE is one of the key factors in D-Psicose production. In the
      present study, the gene AAL45544.1 from Agrobacterium tumefaciens str. C58 was
      modified by artificial synthesis for overexpression in E. coli. The total DPE
      activity reached 3.96 U mL(-1) after optimization of the media composition,
      induction temperature, and concentration of inducer. Furthermore, it was found
      that addition of glycine had a positive effect on the extracellular production of
      DPE, which reached 3.5 U mL(-1). Finally, a two-stage glycerol feeding strategy
      based on both the specific growth rate before induction and the amount of
      glycerol residues after induction was applied in a 3-L fermenter. After a series
      of optimal strategies in the 3-L fermenter, the total and extracellular DPE
      activity were 5.08- and 3.11-fold higher than that noted in the shake flask. The
      extracellular and intracellular DPE activity reached 10.9 and 13.2 U mL(-1),
      achieving 25.5 and 31.1 % conversion of D-fructose to D-psicose, respectively.
      The systemic strategies presented in this study provide valuable novel
      information for the industrial application of DPE.

PMID- 24037041
TI  - The impact of impact factors and the ethics of publication.

PMID- 24037043
TI  - Conducting operational research within a non governmental organization: the
      example of Medecins Sans Frontieres.
AB  - Like many other non governmental organizations (NGOs) that provide assistance to
      vulnerable populations living in difficult and resource-limited settings,
      Medecins Sans Frontieres (MSF) is confronted with situations for which proven,
      effective interventions are often lacking and/or where there is need for strong
      advocacy for improving medical care. As a result, MSF has become an important
      contributor to health research, and has dedicated resources to guide operational
      research by establishing its own Ethics Review Board, an innovation fund, an
      online publications repository and by regularly contributing to major scientific
      conferences. However, this increased research activity has led to concern that
      priorities and resources may be diverted away from the essential mandate of care
      provision for NGOs. In response, this article discusses the potential role
      operational research can play within medical NGOs such as MSF, and highlights the
      relevance of operational research, the essential elements of developing it within
      the organisation and some of the perceived barriers and solutions. 

PMID- 24037042
TI  - Effects of the HN gene C-terminal extensions on the Newcastle disease virus
      virulence.
AB  - The hemagglutinin-neuraminidase (HN) of Newcastle disease virus (NDV) is a
      multifunctional protein that has receptor recognition, neuraminidase, and fusion
      promotion activities. Sequence analysis revealed that the HN gene of many
      extremely low virulence NDV strains encodes a larger open-reading frame (616
      amino acids, aa) with additional 45 aa at its C-terminus when compared with that
      (571 aa) of virulent NDV strains. Therefore, it has been suspected that the 45 aa
      extension at the C-terminus of the HN may affect the NDV virulence. In this
      study, we generated an NDV mesogenic strain Anhinga-based recombinant virus with
      an HN C-terminal extension of 45 aa (rAnh-HN-ex virus) using reverse genetics
      technology. The biological characterization of the recombinant virus showed that
      the rAnh-HN-ex virus had similar growth ability to its parental virus rAnh-wt
      both in embryonating chicken eggs and DF-1 cells. However, the pathogenicity of
      this recombinant virus in embryonating chicken eggs and day-old chickens
      decreased, as evidenced by a longer mean death time and lower intracerebral
      pathogenicity index when compared with the parental virus. This is consistent
      with our previous finding that the recombinant LaSota virus with a 45-aa
      extension at its HN C-terminal was attenuated in chickens and embryonating eggs.
      These results suggest that the HN protein C-terminal extension may contribute to
      the reduced virulence in some low virulence NDV strains. 

PMID- 24037044
TI  - HIV, poverty and women.
AB  - This review examines the interactions of financial status and HIV and its
      implications for women. MEDLINE and Google scholar were searched using the
      keywords 'women', 'poverty' and 'HIV' in any field of the article. The search was
      limited to articles published in English over the last 10 years. The first
      section of the article tries to establish whether poverty or wealth is a risk
      factor for HIV. There is credible evidence for both arguments. While wealth shows
      an increased risk for both sexes, poverty places women at a special disadvantage.
      The second section explains how the financial status interacts with other 'non
      biological' factors to put women at increased risk. While discrimination based on
      these factors disadvantage women, there are some paradoxical observations that do
      not fit with the traditional line of explanation (e.g. paradoxical impact of
      wealth and education on HIV). The final section assesses the impact of HIV in
      driving poverty and the role of women in interventional programmes. The specific
      impact of poverty on females in families living with HIV is less explored. Though
      microfinance initiatives to empower women are a good idea in theory, the actual
      outcome of such a programme is less convincing. 

PMID- 24037045
TI  - Thiamine deficiency and the etiology of tropical ataxic neuropathy.
AB  - Tropical ataxic neuropathy (TAN) is a syndrome characterized by sensory
      polyneuropathy, sensory ataxia, bilateral optic atrophy and bilateral
      sensorineural deafness. The syndrome has occurred in endemic form in several
      African countries, and in epidemic form in Cuba. In endemic communities, the
      syndrome has a high prevalence and a demonstrated risk for high mortality.
      Despite several studies aimed at elucidating the etiological mechanisms of TAN,
      the etiology has remained unknown more than five decades after its original
      description. Chronic cyanide intoxication from a monotonous diet of cassava was
      long thought to be the major etiological factor, but there has been no evidence
      of a causal association. Vitamin deficiencies were thought to play little or no
      role in the pathogenesis of TAN. Evidence from the literature implicating chronic
      thiamine deficiency in the etiology of TAN is presented in this communication.
      This includes evidence of abnormal pyruvate metabolism reversed by thiamine in
      patients with TAN, evidence from erythrocyte transketolase activity indicating
      significant thiamine deficiency in patients with TAN compared to controls, and a
      placebo-controlled trial of therapeutic doses of thiamine which showed a
      clinically dramatic and statistically significant improvement in ataxia. A long
      term thiamine supplementation program for susceptible individuals in endemic
      areas may be effective in the control and eventual eradication of the disease. 

PMID- 24037046
TI  - Reducing the burden of severe neonatal jaundice in G6PD-deficient populations in
      low-income countries: are we doing enough?
AB  - Severe neonatal jaundice (NNJ) remains an important cause of hospitalisation in
      the first week of life particularly in developing countries where glucose-6
      phosphate-dehydrogenase (G6PD) deficiency is prevalent. NNJ is seldom associated
      with mortality when closely monitored but portends significant long-term risks in
      settings where hospitals are ill-equipped to provide phototherapy or exchange
      blood transfusion. Early detection in high-risk populations is an important first
      step towards redressing the current lack of global initiatives on NNJ. Investment
      in the development of low-cost bilirubin monitoring devices, functional
      phototherapy units at first-level health facilities and improved care-seeking
      practices are also essential, particularly in sub-Saharan Africa. 

PMID- 24037047
TI  - Understanding how women's groups improve maternal and newborn health in
      Makwanpur, Nepal: a qualitative study.
AB  - Women's groups, working through participatory learning and action, can improve
      maternal and newborn survival. We describe how they stimulated change in rural
      Nepal and the factors influencing their effectiveness. We collected data from 19
      women's group members, 2 group facilitators, 16 health volunteers, 2 community
      leaders, 21 local men, and 23 women not attending the women's groups, through
      semi-structured interviews, group interviews, focus group discussions and
      unstructured observation of groups. Participants took photographs of their
      locality for discussion in focus groups using photoelicitation methods. Framework
      analysis procedures were used, and data fed back to respondents. When group
      members were compared with 11 184 women who had recently delivered, we found that
      they were of similar socioeconomic status, despite the context of poverty, and
      caste inequalities. Four mechanisms explain the women's group impact on health
      outcomes: the groups learned about health, developed confidence, disseminated
      information in their communities, and built community capacity to take action.
      Women's groups enable the development of a broader understanding of health
      problems, and build community capacity to bring health and development benefit. 

PMID- 24037048
TI  - Referral success among HIV-infected women and HIV-exposed children referred for
      monitoring and treatment in Tanga, Tanzania.
AB  - Long-term retention of patients in the rapidly expanding antiretroviral programs
      against HIV/AIDS is essential for the success of these programs. Unfortunately,
      high percentages of patients in need of treatment are lost to follow up in
      resource-poor settings. From June 2006 to March 2007 269 HIV-infected pregnant
      women were screened for participation in a Prevention of Mother to Child
      Transmission (PMTCT) study in Tanga, Tanzania. Ninety-one women were referred to
      Care and Treatment Center (CTC) for monitoring and antiretroviral therapy
      regardless of inclusion in the PMTCT study. Both women and HIV-exposed children
      were traced at CTC from mid-February to mid-March 2008. Follow-up visits for all
      patients were examined. Only 10% (9/91) of the referred women were still
      attending CTC by February/March 2008 and 64% (58/91) never attended CTC. Not a
      single child could be traced at CTC. The largest loss of patients occurs between
      referral and the first attendance at CTC. Every effort must be made to clarify
      reasons for loss of patients at this point. Further, measures to improve patient
      retention must be increased as must initiatives to improve the ability to trace
      and retain children within the clinics. 

PMID- 24037049
TI  - Increase of imported Leishmaniasis in the Netherlands: a twelve year overview
      (1996-2007).
AB  - Surveillance data indicates that the number of cutaneous (CL), mucocutaneous (ML)
      and visceral leishmaniasis (VL) cases has increased globally and in Europe during
      the past decades. Leishmaniasis is only seen as an imported disease in the
      Netherlands. We investigated occurrence in the Netherlands through an analysis of
      Leishmania patients sent to our laboratory and to the nationwide network of the
      pathology departments between 1996 and 2007. The majority of patients suffered
      from CL, and an outbreak among military personnel stationed in endemic regions in
      2005 was noted. ML was rarely found. However, the occurrence of VL has clearly
      increased. Physicians in non-endemic regions should be aware that leishmaniasis
      can be contracted as close as Southern Europe and that it is not limited to
      tropical and subtropical regions only. 

PMID- 24037050
TI  - Why did many more diamond miners than gold miners die in South Africa during the
      1918 influenza pandemic?
AB  - The very large difference in mortality rates between Kimberley diamond miners and
      Witwatersrand gold miners during the 1918 influenza pandemic has never been
      explained. We examined extant epidemiological records from South African mining
      operations and other related activities to determine if mortality risk factors
      could be measured. During October 1918 when pandemic influenza struck in South
      Africa, the mortality rates in Kimberley diamond miners (22.4%, n = 11 445) were
      >35 times that of Rand gold miners (0.6%, n = 200 000). There were no differences
      discernable between diamond and gold miners regarding their recruitment, working
      conditions, housing or medical care that would explain the great variance in
      mortality rates. Reports of influenza-like illness in Natal Province some weeks
      prior to the main pandemic suggest infection from a mild version of influenza and
      thus protection of the gold miners from mortality whereas the more isolated
      diamond miners only experienced the second, more lethal, wave. The huge mortality
      difference between South African diamond and gold miners in 1918 is most likely
      explained by the circulation of a related but not identical virus to the A/H1N1
      pandemic strain which reached Johannesburg prior to October 1918 because of its
      better transportation connections. 

PMID- 24037051
TI  - Integration of malaria and HIV/AIDS prevention services through the private
      sector in Uganda.
AB  - This study explored whether private midwives can provide prevention of mother-to
      child transmission of human immune deficiency virus (HIV) integrated with malaria
      prevention services in pregnancy, and assess how this affects access and equity
      to services. A household survey supplemented by key informant interviews was
      conducted in Wakiso district, central Uganda from January to April 2009. Results
      show that private midwives are already providing essential maternity services to
      women (antenatal care, 22.0% and delivery care, 19.5%); and they are trusted by
      their communities. Despite this, access to HIV and malaria preventive services
      was low among women in the lowest wealth quintile, the young and the less
      educated. Although private midwives understood the concept of integration, their
      clinics were offering limited integrated services, at 30%. The constraints
      experienced were inadequate skills, high costs of drugs and supplies limiting the
      capacity to have enough stocks, lack of support supervision, low community
      awareness on the importance of seeking antenatal and delivery care from trained
      providers and inadequate support of women by their spouses. In order to improve
      integration, it was recommended that private midwives be given refresher courses;
      improve their capacity to stock essential drugs and supplies; and receive
      supervision and support from the district health authorities. 

PMID- 24037052
TI  - Knowledge and beliefs about onchocerciasis among rural inhabitants in an endemic
      area of Ethiopia.
AB  - A cross-sectional study was conducted to assess the knowledge and beliefs about
      causes, transmission, prevention and control of onchocerciasis among rural
      inhabitants in an endemic area of Ethiopia. Descriptive and quantitative
      information was collected using focus group discussions and a pretested
      structured questionnaire. Onchocerciasis affected and unaffected respondents'
      knowledge and beliefs regarding onchocerciasis were compared. Overall, 75.9%
      (192/253) of study subjects were aware about onchocerciasis. During the survey,
      66.9% of affected, and 45.5% of unaffected respondents knew that onchocerciasis
      was transmitted through blackfly bites. About 53% of unaffected and 60% of
      affected respondents thought that onchocerciasis was preventable and the majority
      of the affected respondents felt that it was curable. Chi-square statistical
      analysis found a significant association between affected and unaffected
      individual's knowledge and beliefs about causes, transmission, prevention and
      control of onchocerciasis. Although the majority of respondents had ample
      awareness, a sizable proportion still had misconceptions and misunderstandings
      about causes, transmission, prevention and control of onchocerciasis. Therefore,
      appropriate communication strategies should be developed to create the awareness
      regarding the role of blackflies in onchocerciasis transmission, the importance
      of proper prevention techniques, early diagnosis and treatment to bring a
      constructive outcome in the near future. 

PMID- 24037053
TI  - Reactive vaccination as an effective tool for measles outbreak control in measles
      mortality reduction settings, Democratic Republic of Congo, 2005-2006.
AB  - New WHO guidelines for measles outbreak response in measles mortality reduction
      settings now include reactive vaccination for outbreaks. Here we used
      surveillance data and vaccine coverage surveys following two mass vaccine
      campaigns in the Democratic Republic of Congo, to show the impact of reactive
      vaccination on reducing cases during outbreaks. The number of measles cases
      reported was collected via the national surveillance system. Following
      vaccination campaigns, two-stage cluster sampling surveys were used to evaluate
      pre and post campaign coverage. In Matadi, 1035 cases were reported from 24
      October 2005 to 19 February 2006 and in Mbuji Mayi, 4734 cases were reported from
      3 October 2005 to 30 April 2006. Following the mass vaccination campaign,
      coverage rose from 87.5% (95% CI 87.2-87.8) to 97.1% (95% CI 96.9-97.3) in Matadi
      and from 74.0% (95% CI 70.9-77.0) to 96.5% (95% CI: 95.7-97.2) in Mbuji Mayi.
      Weekly reported cases reduced respectively by 89.3% and 68.9% in the 3 weeks
      following the mass vaccination campaigns. The introduction of reactive
      vaccination for measles outbreak control provides an additional tool to help
      reduce the impact of outbreaks. Our experience shows that this type of
      intervention is feasible and effective even when baseline vaccination coverage is
      > 70%. 

PMID- 24037054
TI  - Some sociological aspects of cutaneous leishmaniasis in patients attending a
      tertiary referral centre in Colombo, Sri Lanka.
AB  - Over 1800 clinically suspected cases of cutaneous leishmaniasis have been
      referred to the Department of Parasitology, Faculty of Medicine, Colombo, Sri
      Lanka for investigation since 2001. This study analyses some sociological aspects
      of 120 patients with laboratory confirmed cutaneous leishmaniasis. This
      information is important to design and implement control programmes. The disease
      was predominant among males. In females lesions occurred mainly on the face,
      while in men they were seen mainly on the limbs. Immediate medical advice was
      sought by 13% of the population; the others sought treatment when the skin lesion
      grew or failed to heal. Females delayed seeking treatment as they probably
      misinterpreted the lesion as a pimple. Only 39% were referred to a Consultant
      Dermatologist by a medical officer during the first visit. The mean duration of
      time from the detection of the lesion to referral was approximately eight months.
      Psychologically, the presence of the lesion affected less than 20% of
      individuals. Costs related to treatment were relatively low in Sri Lanka. Late
      presentation and diagnostic delay was related to lack of awareness. Educational
      programmes should be carried out, aimed both at health care workers and the
      community to ensure early diagnosis and treatment for cutaneous leishmaniasis. 

PMID- 24037055
TI  - Corrigendum to "Control of the Neglected Tropical Diseases in sub-Saharan Africa:
      the unmet needs" [International Health (2009) 1, 61-70].

PMID- 24037057
TI  - Core-satellite Ag@BaTiO3 nanoassemblies for fabrication of polymer nanocomposites
      with high discharged energy density, high breakdown strength and low dielectric
      loss.
AB  - Dielectric polymer nanocomposites with high dielectric constant have wide
      applications in high energy density electronic devices. The introduction of high
      dielectric constant ceramic nanoparticles into a polymer represents an important
      route to fabricate nanocomposites with high dielectric constant. However, the
      nanocomposites prepared by this method generally suffer from relatively low
      breakdown strength and high dielectric loss, which limit the further increase of
      energy density and energy efficiency of the nanocomposites. In this contribution,
      by using core-satellite structured ultra-small silver (Ag) decorated barium
      titanate (BT) nanoassemblies, we successfully fabricated high dielectric constant
      polymer nanocomposites with enhanced breakdown strength and lower dielectric loss
      in comparison with conventional polymer-ceramic particulate nanocomposites. The
      discharged energy density and energy efficiency are derived from the dielectric
      displacement-electric field loops of the polymer nanocomposites. It is found
      that, by using the core-satellite structured Ag@BT nanoassemblies as fillers, the
      polymer nanocomposites can not only have higher discharged energy density but
      also have high energy efficiency. The mechanism behind the improved electrical
      properties was attributed to the Coulomb blockade effect and the quantum
      confinement effect of the introduced ultra-small Ag nanoparticles. This study
      could serve as an inspiration to enhance the energy storage densities of
      dielectric polymer nanocomposites. 

PMID- 24037056
TI  - Increased levels of IL-6, IL-1beta, and TNF-alpha in Kashin-Beck disease and rats
      induced by T-2 toxin and selenium deficiency.
AB  - The objective of this study is to investigate the possible role of inflammatory
      mediators such as IL-6, IL-1beta, and TNF-alpha in Kashin-Beck disease (KBD)
      children and rats fed with T-2 toxin under a selenium-deficient nutrition status
      in order to determine possible mechanism underlying KBD. Sprague-Dawley rats were
      administered a selenium-deficient diet for 4 weeks prior to their exposure to T-2
      toxin for 4 weeks. The morphology of joint cartilages of KBD children and rats
      was examined by light microscopy, and the expression of proteoglycans was
      determined by histochemical staining. The serum levels of IL-6, IL-1beta, and TNF
      alpha were determined by enzyme-linked immunosorbent assay. IL-6, IL-1beta and
      TNF-alpha were localized by immunohistochemistry, and their mRNA levels were
      detected by real-time RT-PCR. The serum levels of IL-6 were significantly
      elevated in rats fed with selenium-deficient, T-2 toxin, and T-2 toxin plus
      selenium-deficient diets compared to those in the normal diet, while the serum
      levels of IL-1beta and TNF-alpha were significantly increased only in the T-2
      toxin plus selenium-deficient diet group. IL-6, IL-1beta and TNF-alpha protein
      and mRNA levels in cartilage were significantly higher in rats with diets of T-2
      toxin and T-2 toxin plus selenium deficiency than in rats fed normal or selenium
      deficient diet. While staining for the cytokines in cartilages of KBD children
      was significantly higher than that in controls. T-2 toxin under a selenium
      deficient nutritional status induces increased levels of IL-6, IL-1beta, and TNF
      alpha in serum and cartilages, which may account for the pathological mechanism
      underlying the cartilage damage in KBD.

PMID- 24037058
TI  - Crystalens HD intraocular lens analysis using an adaptive optics visual
      simulator.
AB  - PURPOSE: To compare visual and optical quality of the Crystalens HD intraocular
      lens (IOL) with that of a monofocal IOL. METHODS: The wavefront aberration
      patterns of the monocular Akreos Adapt AO IOL and the single-optic accommodating
      Crystalens HD IOL were measured in a model eye. The Crystalens IOL was measured
      in its nonaccommodative state and then, after flexing the haptic to produce 1.4
      mm of movement, in its accommodative state. Using an adaptive optics system,
      subjects' aberrations were removed and replaced with those of pseudophakes
      viewing with either lens. Monocular distance visual acuity (DVA) at high (100%),
      medium (50%), and low (10%) contrast and contrast sensitivity (CS) were measured
      for both IOL optics. Near VA (NVA) and CS were measured for the Crystalens HD IOL
      in its accommodative state. Depth of focus around the distance and near focus was
      also evaluated for the Crystalens HD IOL. Modulation transfer function (MTF),
      point spread function (PSF), and Strehl ratio were also calculated. All measures
      were taken for 3- and 5-mm pupils. RESULTS: The MTF, PSF, and Strehl ratio showed
      comparable values between IOLs (p > 0.05). There were no significant differences
      in DVA and CS between IOLs for all contrasts and pupils (p > 0.05). When
      spherically focused, mean DVA and NVA with the Crystalens HD IOL were >=20/20 at
      100 and 50% contrasts for both pupils. Monocular DVA, NVA, and CS were slightly
      better with 3- than 5-mm pupils, but without statistically significant
      differences. The Crystalens HD IOL showed about 0.75 and 0.50 D of depth of focus
      in its accommodative state and nonaccommodative state, respectively. CONCLUSIONS:
      The optical and visual quality with the nonaccommodatied Crystalens HD IOL was
      comparable to that of a monofocal IOL. If this lens can move 1.4 mm in the eye,
      it will provide high-quality optics for near vision as well.

PMID- 24037059
TI  - Visual performance with lenses correcting peripheral refractive errors.
AB  - PURPOSE: To design and manufacture lenses to correct peripheral refraction along
      the horizontal meridian and to determine whether these resulted in noticeable
      improvements in visual performance. METHODS: Subjective refraction of a low myope
      was determined on the basis of best peripheral detection acuity along the
      horizontal visual field out to +/-30 degrees  for both horizontal and vertical
      gratings. Subjective refraction was compared to objective refractions using a
      COAS-HD aberrometer. Special lenses were made to correct peripheral refraction,
      based on designs optimized with and without smoothing across a 3-mm diameter
      square aperture. Grating detection was retested with these lenses. Contrast
      thresholds of 1.25-min arc spots were determined across the field for the
      conditions of best correction, on-axis correction, and the special lenses.
      RESULTS: The participant had high relative peripheral hyperopia, particularly in
      the temporal visual field (maximum, 2.9 D). There were differences >0.5 D between
      subjective and objective refractions at a few field angles. On-axis correction
      reduced peripheral detection acuity and increased peripheral contrast threshold
      in the peripheral visual field, relative to the best correction, by up to 0.4 and
      0.5 log units, respectively. The special lenses restored most of the peripheral
      vision, although not all at angles to +/-10 degrees , and with the lens optimized
      with aperture smoothing possibly giving better vision than the lens optimized
      without aperture smoothing at some angles. CONCLUSIONS: It is possible to design
      and manufacture lenses to give near-optimum peripheral visual performance to at
      least +/-30 degrees  along one visual field meridian. The benefit of such lenses
      is likely to be manifest only if a subject has a considerable relative peripheral
      refraction, for example, of the order of 2 D.

PMID- 24037060
TI  - Factors affecting eye care-seeking behavior of parents for their children.
AB  - PURPOSE: Most of the causes of childhood blindness are either treatable or
      preventable. Eye care-seeking behavior (ESB) of parents for their children plays
      a pivotal role in reducing this problem. This study was done because there was a
      sparsity of literature in this context and with a view to help eye care
      professionals plan better programs and to identify factors facilitating and/or
      hindering ESB of parents for their school-going children in an urban area.
      METHODS: This study adopted a qualitative snapshot narrative study design. In
      depth interviews and focus group discussions were conducted in areas of Chennai
      with parents and eye care professionals selected through stratified purposive
      sampling. Parents were based on those who sought care and did not seek care after
      a school eye screening program and on their socioeconomic status. Data were
      transcribed to English, familiarized, and inductive coded, and themes were
      formed. Redundancy was considered as end point of data collection. RESULTS: Two
      focus group discussions and 11 in-depth interviews were conducted. Squint,
      redness or watering of eyes, eye irritation, headache, family history of ocular
      diseases, severity, and repetitiveness of symptoms facilitate parents seeking eye
      care for their wards/children. Economic status was an important barrier reported
      to affect the ESB. Logistic factors like taking appointment with doctor, taking
      leave from work, transport, and traveling distance were noted. CONCLUSIONS: This
      study shows the facilitating factors and barriers for ESB of the Chennai urban
      parents for their wards. The results suggest that efforts needed to be put to
      overcome the barriers through planned awareness programs.

PMID- 24037061
TI  - Spherical aberration and the sign of defocus.
AB  - PURPOSE: Visual sensing of the sign of defocus is important not only for the
      rapid control of accommodation but also for regulating the slower long-term
      growth of the eye. METHODS: We examined the possibility that ocular spherical
      aberration (SA) elicits a sign of defocus by optical modeling of image formation
      using the principles of physical optics. RESULTS: Retinal image contrast, as
      measured by the area under the visually weighted modulation-transfer function,
      depends on both the magnitude and the sign of defocus relative to the sign of the
      SA. Image contrast is greater for hyperopic blur than for myopic blur when SA is
      positive and vice versa when SA is negative. CONCLUSIONS: When coupled with
      Wallman's hypothesis that retinal activity caused by image contrast inhibits eye
      growth, these results provide a testable hypothesis to account for myopia
      progression. For example, we suggest that hyperopic blur is a risk factor for
      myopia progression only when the eye has a negative SA because that is the
      combination leading to relatively low contrast in the defocused retinal image.
      Because the likelihood of a negative SA increases with accommodation, avoiding
      long hours of near work in the presence of accommodative lag may help prevent the
      onset and progression of myopia.

PMID- 24037062
TI  - Central and paracentral corneal curvature changes during orthokeratology.
AB  - PURPOSE: To investigate regional changes in corneal curvature and power induced
      by overnight orthokeratology (OK) contact lens wear over a period of 2 weeks.
      METHODS: Corneal topography data (Medmont E300) from 21 myopes (12 M, 9F, 20 to
      40 years), who had worn BE OK lenses manufactured in Boston XO material for 14
      nights, were analyzed retrospectively. Enrollment criteria were myopia up to 4.50
      D and corneal toricity up to 1.50 D. Custom MATLAB programs were used to
      determine sectorial tangential curvature and refractive power, and to investigate
      changes from baseline after 1 and 14 nights, and between 1 and 14 nights of lens
      wear in the central circular zone (CCZ) and surrounding paracentral annular zone
      (PCZ), with each zone subdivided into nasal, superior, temporal, and inferior
      sectors. RESULTS: After OK, significant asymmetry was found in tangential
      curvature across sectors. In the CCZ, by day 14 there was greater flattening in
      the temporal (-1.27 +/- 0.62 D, p < 0.001) than nasal sector (0.05 +/- 0.62 D, p
      = 0.893). In the PCZ, by day 14 there was greater steepening in the temporal
      (2.37 +/- 1.09 D, p < 0.001) than nasal sector (0.30 +/- 1.36 D, p = 0.326). In
      both zones, vertical sectors did not show any asymmetry. The variation in corneal
      curvature across sectors and the mirror asymmetry was also reflected in
      variations in the corneal refractive power. CONCLUSIONS: OK induces non-uniform
      corneal changes to the central and paracentral regions. This non-uniformity may
      influence peripheral refraction profiles reported with OK that have been
      suggested to be influential in myopia control.

PMID- 24037063
TI  - Factors preventing myopia progression with orthokeratology correction.
AB  - PURPOSE: To examine which baseline measurements constitute predictive factors for
      axial length growth over 2 years in children wearing orthokeratology contact
      lenses (OK) and single-vision spectacles (SV). METHODS: Sixty-one children were
      prospectively assigned to wear either OK (n = 31) or SV (n = 30) for 2 years. The
      primary outcome measure (dependent variable) was axial length change at 2 years
      relative to baseline. Other measurements (independent variables) were age, age of
      myopia onset, gender, myopia progression 2 years before baseline and baseline
      myopia, anterior chamber depth, corneal power and shape (p value), and iris and
      pupil diameters as well as parental refraction. The contribution of all
      independent variables to the 2-year change in axial length was assessed using
      univariate and multivariate regression analyses. RESULTS: After univariate
      analyses, smaller increases in axial length were found in the OK group compared
      to the SV group in children who were older, had earlier onset of myopia, were
      female, had lower rate of myopia progression before baseline, had less myopia at
      baseline, had longer anterior chamber depth, had greater corneal power, had more
      prolate corneal shape, had larger iris diameter, had larger pupil sizes, and had
      lower levels of parental myopia (all p < 0.05). In multivariate analyses, older
      age and greater corneal power were associated with smaller increases in axial
      length in the OK group (both p < 0.05), whereas in SV wearers, smaller iris
      diameter was associated with smaller increases in axial length (p = 0.021).
      CONCLUSIONS: Orthokeratology is a successful treatment option in controlling
      axial elongation compared to SV in children of older age, had earlier onset of
      myopia, were female, had lower rate of myopia progression before baseline, had
      lower myopia at baseline, had longer anterior chamber depth, had greater corneal
      power, had more prolate corneal shape, had larger iris and pupil diameters, and
      had lower levels of parental myopia.

PMID- 24037064
TI  - Calculation of ion currents across the inner membrane of functionally intact
      mitochondria.
AB  - Mitochondrial ion transport systems play a central role in cell physiology. Rates
      of Ca (2+) and K(+) transport across the inner mitochondrial membrane have been
      derived from the measurement of ion accumulation over time within functional
      isolated mitochondria or mitochondria of cultured cells. Alternatively, the
      electrical currents generated by ionic flux have been directly measured in
      purified and swollen mitochondrial samples (mitoplasts) or reconstituted
      channels, and typically range from 1 pA to several 100s pA. However, the direct
      electrophysiological approach necessarily requires extensive processing of the
      mitochondria prior to measurement, which can only be performed on isolated
      mitoplasts. To compare rates of mitochondrial ion transport measured in
      electrophysiological experiments to those measured in intact mitochondria and
      cells, we converted published rates of mitochondrial ion uptake into units of
      ionic current. We estimate that for monovalent ions, uptake by intact
      mitochondria at the rate of 1 nmol ? mg(-1) protein ? min(-1) is equivalent to
      0.2 fA of current per whole single mitochondrion (0.4 fA for divalent ions). In
      intact mitochondria, estimated rates of electrogenic cation uptake are limited to
      1-100 fA of integral current per single mitochondrion. These estimates are orders
      of magnitude lower than the currents through mitochondrial channels directly
      measured via patch-clamp or artificial lipid bilayer approaches. 

PMID- 24037065
TI  - Hydroxyethyl starch-induced pruritus: clinical characteristics and influence of
      dose, molecular weight and substitution.
AB  - Severe persistent pruritus is a common, but incompletely characterized,
      complication of hydroxyethyl starch (HES) infusion. This retrospective study
      aimed to assess HES-induced pruritus by electron microscopic findings, pruritus
      characteristics, and response to stimuli, and to determine the impact of HES
      dosage, molecular weight and substitution. Seventy patients with electron micro
      scopy-proven HES-induced pruritus were included. HES-laden vacuoles were observed
      in skin macrophages of all patients. The median latency between HES exposure and
      pruritus onset was 3 weeks, and the median duration of pruritus was 6 months.
      Pruritus was severe, or very severe, in 80% of patients. Mechanical stimuli
      triggered pruritus in 74% of patients. Although the median cumulative dose of HES
      was 300 g, 15% of patients developed pruritus after only 30 g. There were no
      significant differences between HES 130/0.4 and HES 200/0.5 in pruritus latency,
      duration or severity. HES-induced pruritus thus may occur at any dose, molecular
      weight or substitution.

PMID- 24037066
TI  - Thermal analysis of bulk filled composite resin polymerization using various
      light curing modes according to the curing depth and approximation to the cavity
      wall.
AB  - OBJECTIVE: The purpose of this study was to investigate the polymerization
      temperature of a bulk filled composite resin light-activated with various light
      curing modes using infrared thermography according to the curing depth and
      approximation to the cavity wall. MATERIAL AND METHODS: Composite resin
      (AeliteFlo, Bisco, Schaumburg, IL, USA) was inserted into a Class II cavity
      prepared in the Teflon blocks and was cured with a LED light curing unit (Dr's
      Light, GoodDoctors Co., Seoul, Korea) using various light curing modes for 20 s.
      Polymerization temperature was measured with an infrared thermographic camera
      (Thermovision 900 SW/TE, Agema Infra-red Systems AB, Danderyd, Sweden) for 40 s
      at measurement spots adjacent to the cavity wall and in the middle of the cavity
      from the surface to a 4 mm depth. Data were analyzed according to the light
      curing modes with one-way ANOVA, and according to curing depth and approximation
      to the cavity wall with two-way ANOVA. RESULTS: The peak polymerization
      temperature of the composite resin was not affected by the light curing modes.
      According to the curing depth, the peak polymerization temperature at the depth
      of 1 mm to 3 mm was significantly higher than that at the depth of 4 mm, and on
      the surface. The peak polymerization temperature of the spots in the middle of
      the cavity was higher than that measured in spots adjacent to the cavity wall.
      CONCLUSION: In the photopolymerization of the composite resin, the temperature
      was higher in the middle of the cavity compared to the outer surface or at the
      internal walls of the prepared cavity.

PMID- 24037067
TI  - Effect of silica coating and silane surface treatment on the bond strength of
      soft denture liner to denture base material.
AB  - OBJECTIVE: This study investigated the effects of different surface treatments on
      the tensile bond strength of an autopolymerizing silicone denture liner to a
      denture base material after thermocycling. MATERIAL AND METHODS: Fifty
      rectangular heat-polymerized acrylic resin (QC-20) specimens consisting of a set
      of 2 acrylic blocks were used in the tensile test. Specimens were divided into 5
      test groups (n=10) according to the bonding surface treatment as follows: Group
      A, adhesive treatment (Ufi Gel P adhesive) (control); Group S, sandblasting using
      50-um Al2O3; Group SCSIL, silica coating using 30-um Al2O3 modified by silica and
      silanized with silane agent (CoJet System); Group SCA, silica coating and
      adhesive application; Group SCSILA, silica coating, silane and adhesive
      treatment. The 2 PMMA blocks were placed into molds and the soft lining materials
      (Ufi Gel P) were packed into the space and polymerized. All specimens were
      thermocycled (5,000 cycles) before the tensile test. Bond strength data were
      analyzed using 1-way ANOVA and Duncan tests. Fracture surfaces were observed by
      scanning electron microscopy. X-ray photoelectron spectrometer (XPS) and Fourier
      Transform Infrared spectrometer (FTIR) analysis were used for the chemical
      analysis and a profilometer was used for the roughness of the sample surfaces.
      RESULTS: The highest bond strength test value was observed for Group A (1.35+/
      0.13); the lowest value was for Group S (0.28+/-0.07) and Group SCSIL (0.34+/
      0.03). Mixed and cohesive type failures were seen in Group A, SCA and SCSILA.
      Group S and SCSIL showed the least silicone integrations and the roughest
      surfaces. CONCLUSION: Sandblasting, silica coating and silane surface treatments
      of the denture base resin did not increase the bond strength of the silicone
      based soft liner. However, in this study, the chemical analysis and surface
      profilometer provided interesting insights about the bonding mechanism between
      the denture base resin and silicone soft liner.

PMID- 24037068
TI  - Load-bearing capacity of screw-retained CAD/CAM-produced titanium implant
      frameworks (I-Bridge(r)2) before and after cyclic mechanical loading.
AB  - Implant-supported screw-retained fixed dental prostheses (FDPs) produced by CAD/
      CAM have been introduced in recent years for the rehabilitation of partial or
      total endentulous jaws. However, there is a lack of data about the long-term
      mechanical characteristics. OBJECTIVE: The aim of this study was to investigate
      the failure mode and the influence of extended cyclic mechanical loading on the
      load-bearing capacity of these frameworks. MATERIAL AND METHODS: Ten five-unit
      FDP frameworks simulating a free-end situation in the mandibular jaw were
      manufactured according to the I-Bridge(r)2-concept (I-Bridge(r)2, Biomain AB,
      Helsingborg, Sweden) and each was screw-retained on three differently angulated
      Astra Tech implants (30o buccal angulation/0o angulation/30o lingual angulation).
      One half of the specimens was tested for static load-bearing capacity without any
      further treatment (control), whereas the other half underwent five million cycles
      of mechanical loading with 100 N as the upper load limit (test). All specimens
      were loaded until failure in a universal testing machine with an occlusal force
      applied at the pontics. Load-displacement curves were recorded and the failure
      mode was macro- and microscopically analyzed. The statistical analysis was
      performed using a t-test (p=0.05). RESULTS: All the specimens survived cyclic
      mechanical loading and no obvious failure could be observed. Due to the cyclic
      mechanical loading, the load-bearing capacity decreased from 8,496 N+/-196 N
      (control) to 7,592 N+/-901 N (test). The cyclic mechanical loading did not
      significantly influence the load-bearing capacity (p=0.060). The failure mode was
      almost identical in all specimens: large deformations of the framework at the
      implant connection area were obvious. CONCLUSION: The load-bearing capacity of
      the I-Bridge(r)2 frameworks is much higher than the clinically relevant occlusal
      forces, even with considerably angulated implants. However, the performance under
      functional loading in vivo depends on additional aspects. Further studies are
      needed to address these aspects.

PMID- 24037069
TI  - Comparison of static friction with self-ligating, modified slot design and
      conventional brackets.
AB  - OBJECTIVE: To compare the static frictional forces generated at the bracket/wire
      interface of stainless steel brackets with different geometries and angulations,
      combined with orthodontic wires of different diameters. MATERIAL AND METHODS: The
      frictional forces were evaluated with three different types of metal brackets: a
      passive self-ligating (SmartClipTM, 3M/Unitek, Monrovia, USA), with a modified
      slot design (Mini Uni TwinTM, 3M/Unitek, Monrovia, USA) and conventional (Kirium,
      Abzil, Sao Jose do Rio Preto, Brazil). The samples were mounted in a testing
      device with three different angulations and tested with 0.014" and 0.018"
      stainless steel wires (American Orthodontics, Sheboygan, USA). The static
      frictional force was measured using a universal testing machine (DL 500, EMIC(r),
      Sao Jose dos Pinhais, Brazil) with a crosshead speed of 1 mm/min. Statistical
      analysis was performed by two-way ANOVA followed by Bonferroni's post hoc test.
      RESULTS: There was a significant difference (p<0.05) in static friction when the
      three types of brackets were tested with the same wire size. The wire diameter
      influenced friction only when the brackets had a 10o angulation (p<0.05). The
      angulation influenced friction (p<0.05) when the brackets were associated with a
      0.018" wire. CONCLUSION: Brackets with a modified slot design showed intermediate
      static frictional force values between the conventional and self-ligating
      brackets tested.

PMID- 24037070
TI  - Factors affecting the bond strength of denture base and reline acrylic resins to
      base metal materials.
AB  - OBJECTIVE: The shear bond strengths of two hard chairside reline resin materials
      and an auto-polymerizing denture base resin material to cast Ti and a Co-Cr alloy
      treated using four conditioning methods were investigated. MATERIAL AND METHODS:
      Disk specimens (diameter 10 mm and thickness 2.5 mm) were cast from pure Ti and
      Co-Cr alloy. The specimens were wet-ground to a final surface finish of 600 grit,
      air-dried, and treated with the following bonding systems: 1) air-abraded with 50
      70-um grain alumina (CON); 2) 1) + conditioned with a primer, including an acidic
      phosphonoacetate monomer (MHPA); 3) 1) + conditioned with a primer including a
      diphosphate monomer (MDP); 4) treated with a tribochemical system. Three resin
      materials were applied to each metal specimen. Shear bond strengths were
      determined before and after 10,000 thermocycles. RESULTS: The strengths decreased
      after thermocycling for all combinations. Among the resin materials assessed, the
      denture base material showed significantly (p<0.05) greater shear bond strengths
      than the two reline materials, except for the CON condition. After 10,000
      thermocycles, the bond strengths of two reline materials decreased to less than
      10 MPa for both metals. The bond strengths of the denture base material with MDP
      were sufficient: 34.56 MPa for cast Ti and 38.30 for Co-Cr alloy. CONCLUSION:
      Bonding of reline resin materials to metals assessed was clinically insufficient,
      regardless of metal type, surface treatment, and resin composition. For the
      relining of metal denture frameworks, a denture base material should be used.

PMID- 24037071
TI  - Antimicrobial and fluoride release capacity of orthodontic bonding materials.
AB  - OBJECTIVE: The aim of this study was to evaluate the antimicrobial and fluoride
      releasing capacity of 3 bonding materials. MATERIAL AND METHODS: Thirty nine
      specimens with standardized surface smoothness and dimensions were prepared. The
      antimicrobial capacity of the materials against S. mutans, L. casei and C.
      albicans was evaluated by determining the percentage of growth inhibition of
      these microorganisms in an inoculated medium, obtained by optical density
      readouts on a spectrophotometer. The potential to interfere in microbial growth
      on the surface of the studied materials was observed by means of scanning
      electron microscopy (SEM). The fluoride release capacity in ultrapure water for
      14 days was analyzed by means of ion chromatography. RESULTS: The PLUS group
      presented the highest percentage of microbial inhibition and the most
      contamination-free surface. The FUJI group presented the best fluoride release
      capacity. CONCLUSIONS: The TransbondTM Plus Color Change was the one that
      presented the best general behavior considering the evaluated aspects.

PMID- 24037072
TI  - Heat treatment following surface silanization in rebonded tribochemical silica
      coated ceramic brackets: shear bond strength analysis.
AB  - OBJECTIVE: This study aimed to evaluate the effects of heat treatment on the
      tribochemical silica coating and silane surface conditioning and the bond
      strength of rebonded alumina monocrystalline brackets. MATERIAL AND METHODS:
      Sixty alumina monocrystalline brackets were randomly divided according to
      adhesive base surface treatments (n=20): Gc, no treatment (control); Gt,
      tribochemical silica coating + silane application; Gh, as per Gt + post-heat
      treatment (air flux at 100oC for 60 s). Brackets were bonded to the enamel
      premolars surface with a light-polymerized resin and stored in distilled water at
      37oC for 100 days. Additionally, half the specimens of each group were
      thermocycled (6,000 cycles between 5-55oC) (TC). The specimens were submitted to
      the shear bond strength (SBS) test using a universal testing machine (1 mm/min).
      Failure mode was assessed using optical and scanning electron microscopy (SEM),
      together with the surface roughness (Ra) of the resin cement in the bracket using
      interference microscopy (IM). 2-way ANOVA and the Tukey test were used to compare
      the data (p>0.05). RESULTS: The strategies used to treat the bracket surface had
      an effect on the SBS results (p=0.0), but thermocycling did not (p=0.6974).
      Considering the SBS results (MPa), Gh-TC and Gc showed the highest values
      (27.59+/-6.4 and 27.18+/-2.9) and Gt-TC showed the lowest (8.45+/-6.7). For the
      Ra parameter, ANOVA revealed that the aging method had an effect (p=0.0157) but
      the surface treatments did not (p=0.458). For the thermocycled and non
      thermocycled groups, Ra (um) was 0.69+/-0.16 and 1.12+/-0.52, respectively. The
      most frequent failure mode exhibited was mixed failure involving the enamel-resin
      bracket interfaces. CONCLUSION: Regardless of the aging method, Gh promoted
      similar SBS results to Gc, suggesting that rebonded ceramic brackets are a more
      effective strategy.

PMID- 24037073
TI  - The sealing ability of MTA apical plugs exposed to a phosphate-buffered saline.
AB  - OBJECTIVE: The aim of this study was to evaluate the influence of exposure of the
      mineral trioxide aggregate (MTA) - with and without calcium chloride (CaCl2) - to
      phosphate-buffered saline (PBS) on the apical microleakage using a glucose
      leakage system. MATERIAL AND METHODS: Sixty root segments were randomly divided
      into 4 experimental groups (n=15). After resecting the apical segments and
      enlarging the canals with Gates-Glidden drills, the apical cavities were filled
      with MTA with or without CaCl2 and the root canals were dressed with a moistened
      cotton pellet or PBS, as follows: 1) MTA/cotton pellet; 2) MTA/PBS; 3)
      MTA+10%CaCl2/cotton pellet; 4) MTA+10%CaCl2/PBS. All root segments were
      introduced in floral foams moistened with PBS. After 2 months, all root segments
      were prepared to evaluate the glucose leakage along the apical plugs. The amount
      of glucose leakage was measured following an enzymatic reaction and quantified by
      a spectrophotometer. Four roots were used as controls. The data were analyzed
      using Kruskal-Wallis and Mann-Whitney tests (p<0.05). RESULTS: There were no
      differences between groups 1 and 2 (p>0.05), and 3 and 4 (p>0.05). The addition
      of CaCl2 to the MTA significantly decreased its sealing ability (p<0.05).
      CONCLUSION: The interaction with PBS did not improve the MTA sealing ability. The
      addition of CaCl2 to the MTA negatively influenced the apical seal.

PMID- 24037074
TI  - The efficacy of the self-adjusting file and ProTaper for removal of calcium
      hydroxide from root canals.
AB  - OBJECTIVE: The goal of this study was to evaluate the efficacy of the Self
      Adjusting File (SAF) and ProTaper for removing calcium hydroxide [Ca(OH)2] from
      root canals. MATERIAL AND METHODS: Thirty-six human mandibular incisors were
      instrumented with the ProTaper system up to instrument F2 and filled with a
      Ca(OH)2-based dressing. After 7 days, specimens were distributed in two groups
      (n=15) according to the method of Ca(OH)2 removal. Group I (SAF) was irrigated
      with 5 mL of NaOCl and SAF was used for 30 seconds under constant irrigation with
      5 mL of NaOCl using the Vatea irrigation device, followed by irrigation with 3 mL
      of EDTA and 5 mL of NaOCl. Group II (ProTaper) was irrigated with 5 mL of NaOCl,
      the F2 instrument was used for 30 seconds, followed by irrigation with 5 mL of
      NaOCl, 3 mL of EDTA, and 5 mL of NaOCl. In 3 teeth Ca(OH)2 was not removed
      (positive control) and in 3 teeth canals were not filled with Ca(OH)2 (negative
      control). Teeth were sectioned and prepared for the scanning electron microscopy.
      The amounts of residual Ca(OH)2 were evaluated in the middle and apical thirds
      using a 5-score system. RESULTS: None of the techniques completely removed the
      Ca(OH)2 dressing. No difference was observed between SAF and ProTaper in removing
      Ca(OH)2 in the middle (P=0.11) and the apical (P=0.23) thirds. CONCLUSION: The
      SAF system showed similar efficacy to rotary instrument for removal of Ca(OH)2
      from mandibular incisor root canals.

PMID- 24037075
TI  - Human tooth germ stem cell response to calcium-silicate based endodontic cements.
AB  - OBJECTIVE: The aim of this study was to compare the cytotoxic effects of
      endodontic cements on human tooth germ stem cells (hTGSCs). MTA Fillapex, a
      mineral trioxide aggregate (MTA)-based, salicylate resin containing root canal
      sealer, was compared with iRoot SP, a bioceramic sealer, and AH Plus Jet, an
      epoxy resin-based root canal sealer. MATERIAL AND METHODS: To evaluate
      cytotoxicity, all materials were packed into Teflon rings (4 mmu3 mm) and co
      cultured with hTGSCs with the aid of 24-well Transwell permeable supports, which
      had a pore size of 0.4 um. Coverslips were coated with MTA Fillapex, iRoot SP and
      AH Plus Jet and each coverslip was placed onto the bottom of one well of a six
      well plate for scanning electron microscopy (SEM) analysis. Before the
      cytotoxicity and SEM analysis, all samples were stored at 37oC and at 95%
      humidity and 5% CO2 for 24 hours to set. The cellular viability was analyzed
      using MTS test (3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4
      sulfo-phenyl)-2H-tetrazolium). The cytotoxic effects and SEM visualization of the
      tested materials were analyzed at 24-hour, 72-hour, one-week and two-week
      periods. RESULTS: On the 1st day, only MTA Fillapex caused cytotoxicity compared
      to negative control (NC) group (p<0.008). No significant difference was observed
      between the other tested materials at this period (p>0.05). After 14 days of
      incubation with the test materials, MTA Fillapex exhibited significantly higher
      cytotoxicity compared with iRoot SP, AH Plus Jet and the NC group (P<0.008). In
      the SEM analysis, the highest levels of cell attachment were observed for iRoot
      SP and the control group. After 24 hours, MTA Fillapex reduced the number of
      cells attached to the surface. CONCLUSIONS: Within the limitations of this study,
      sealers exerted different cytotoxic effects on hTGSCs. Although all materials
      have exerted cellular toxicity, iRoot SP and AH Plus Jet may promote better
      attachment to hTGSCs.

PMID- 24037076
TI  - Validation of a physical anthropology methodology using mandibles for gender
      estimation in a Brazilian population.
AB  - Validation studies of physical anthropology methods in the different population
      groups are extremely important, especially in cases in which the population
      variations may cause problems in the identification of a native individual by the
      application of norms developed for different communities. OBJECTIVE: This study
      aimed to estimate the gender of skeletons by application of the method of
      Oliveira, et al. (1995), previously used in a population sample from Northeast
      Brazil. MATERIAL AND METHODS: The accuracy of this method was assessed for a
      population from Southeast Brazil and validated by statistical tests. The method
      used two mandibular measurements, namely the bigonial distance and the mandibular
      ramus height. The sample was composed of 66 skulls and the method was applied by
      two examiners. The results were statistically analyzed by the paired t test,
      logistic discriminant analysis and logistic regression. RESULTS: The results
      demonstrated that the application of the method of Oliveira, et al. (1995) in
      this population achieved very different outcomes between genders, with 100% for
      females and only 11% for males, which may be explained by ethnic differences.
      However, statistical adjustment of measurement data for the population analyzed
      allowed accuracy of 76.47% for males and 78.13% for females, with the creation of
      a new discriminant formula. CONCLUSION: It was concluded that methods involving
      physical anthropology present high rate of accuracy for human identification,
      easy application, low cost and simplicity; however, the methodologies must be
      validated for the different populations due to differences in ethnic patterns,
      which are directly related to the phenotypic aspects. In this specific case, the
      method of Oliveira, et al. (1995) presented good accuracy and may be used for
      gender estimation in Brazil in two geographic regions, namely Northeast and
      Southeast; however, for other regions of the country (North, Central West and
      South), previous methodological adjustment is recommended as demonstrated in this
      study.

PMID- 24037077
TI  - Supplementation of soft drinks with metallic ions reduces dissolution of bovine
      enamel.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of the addition of
      metallic ions to carbonated drinks on their erosive potential. MATERIAL AND
      METHODS: Powdered enamel was added to carbonated beverages (Coca-ColaTM or Sprite
      ZeroTM and shaken for 30 s. The samples were then immediately centrifuged and the
      supernatant removed. This procedure was repeated 5 times with the beverages
      containing Cu2+, Mg2+, Mn2+ or Zn2+ (1.25-60 mmol/L). For Coca-ColaTM, the
      concentration of each ion that exhibited the highest protection was also
      evaluated in combination with Fe2+. The phosphate or calcium released were
      analyzed spectrophotometrically. Data were analyzed using ANOVA and Tukey's test
      (p<0.05). RESULTS: For Coca-ColaTM, the best protective effect was observed for
      Zn2+ alone (10 mmol/L) or in combination (1 mmol/L) with other ions (12% and 27%,
      respectively, when compared with the control). Regarding Sprite ZeroTM, the best
      protective effect was observed for Cu2+ at 15 and 30 mmol/L, which decreased the
      dissolution by 22-23%. Zn2+ at 2.5 mmol/L also reduced the dissolution of
      powdered enamel by 8%. CONCLUSIONS: The results suggest that the combination of
      metallic ions can be an alternative to reduce the erosive potential of Coca
      ColaTM. Regarding Sprite ZeroTM, the addition of Cu2+ seems to be the best
      alternative.

PMID- 24037078
TI  - Bond strength to root dentin and fluid filtration test of AH Plus/gutta-percha,
      EndoREZ and RealSeal systems.
AB  - OBJECTIVES: To investigate the bond strength and seal ability produced by AH
      Plus/gutta-percha, EndoREZ and RealSeal systems to root canal dentin. MATERIAL
      AND METHODS: Sixty extracted single-root human teeth, instrumented manually to
      size 40, were divided into three groups (n=20) according to the sealer used; G1:
      AH Plus, G2: EndoREZ, and G3: RealSeal sealers. After filling using the lateral
      condensation technique, each sealer group was randomly divided into two subgroups
      according to the tests applied (n=10 for uPush-out test and n=10 for fluid
      filtration test). A fluid filtration method was used for quantitative evaluation
      of apical leakage. Four 1-mm-thick slices (cervical and medium level) were
      obtained from each root sample and a uPush-out test was performed. Failure modes
      were examined under microscopy at 40x, and a one-way ANOVA was applied to analyze
      the permeability. Non-parametrical statistics for related (Friedman's and
      Wilcoxon's rank tests) or unrelated samples (Kruskal-Wallis' and Mann-Whitney's
      tests) allowed for comparisons of uPush-out strength values among materials at
      the different levels. Statistical significance was accepted for p values <.05.
      RESULTS: There are no significant differences among fluid filtration of the three
      sealers. The sealer/core material does not significantly influence the uPush-out
      bond strength values (F=2.49; p=0.10), although statistically significant
      differences were detected with regard to root level (Chi2=23.93; p<0.001). AH
      Plus and RealSeal obtained higher bond strength to intraradicular dentin in the
      medium root slices. CONCLUSIONS: There are no significant differences between the
      permeability and global uPush-out bond strength to root canal dentin achieved by
      AH Plus/gutta-percha, EndoREZ and RealSeal systems.

PMID- 24037079
TI  - High and specialty-related musculoskeletal disorders afflict dental professionals
      even since early training years.
AB  - OBJECTIVE: To determine how early musculoskeletal disorders (MSDs) develop in
      dental professionals and to explore the potential differences among distinct
      dental specialties. MATERIAL AND METHODS: 271 dental postgraduates majoring in
      five dental specialties were recruited, i.e., orthodontics, prosthodontics,
      endodontics, periodontics and alveolar surgery. 254 age-matched non-dental
      postgraduates served as the control. The standardized Nordic questionnaire on
      MSDs and a self-report questionnaire regarding correlative factors (only for
      dental postgraduates) were answered through emails. Reliability of responses was
      assessed applying test-retest method. RESULTS: The intraclass correlation
      coefficient of participants' answers ranged from 0.89 to 0.96. Dental
      postgraduates had significantly higher prevalence of MSDs than the control group,
      especially at neck, upper back and lower back. In all dental specialties
      included, high prevalence of MSDs was reported at neck (47.5%-69.8%), shoulders
      (50.8%-65.1%), lower back (27.1%-51.2%) and upper back (25.6%-46.5%), with lower
      prevalence at elbows (5.1%-18.6%), hips (3.4%-16.3%) and ankles (5.1%-11.6%).
      Periodontics students reported the worst MSDs in most body regions except wrists
      and knees, which were more prevalent for prosthodontic and alveolar surgery
      students, respectively. Furthermore, year of clinical work, clinical hours per
      week and desk hours per week were found as risk factors for MSDs, whereas
      physical exercise and rest between patients as protective factors. CONCLUSIONS:
      High and specialty-related MSDs afflict dental professionals even since very
      early stage of careers. Prevention aimed at the specialty-related characteristics
      and the risk/protective factors revealed in this study should be introduced to
      dental personnel as early as possible.

PMID- 24037080
TI  - Rehabilitative treatment of cleft lip and palate: experience of the Hospital for
      Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP) - Part 5: institutional
      outcomes assessment and the role of the Laboratory of Physiology.
AB  - The Laboratory of Physiology provides support for the diagnosis of functional
      disorders associated with cleft lip and palate and also conducts studies to
      assess, objectively, the institutional outcomes, as recommended by the World
      Health Organization. The Laboratory is conceptually divided into three units,
      namely the Unit for Upper Airway Studies, Unit for Stomatognathic System Studies
      and the Unit for Sleep Studies, which aims at analyzing the impact of different
      surgical and dental procedures on the upper airways, stomatognathic system and
      the quality of sleep of individuals with cleft lip and palate. This paper
      describes the main goals of the Laboratory in the assessment of procedures which
      constitute the basis of the rehabilitation of cleft lip and palate, i.e., Plastic
      Surgery, Orthodontics and Maxillofacial Surgery and Speech Pathology. 

PMID- 24037081
TI  - Multi-purpose materials in dentistry - is it possible to match maximum mechanical
      and biological properties/performance?

PMID- 24037082
TI  - The diaryl oxazole PC-046 is a tubulin-binding agent with experimental anti-tumor
      efficacy in hematologic cancers.
AB  - Microtubule targeting agents are among the most widely used chemotherapeutics for
      both solid and hematological malignancies. This study characterizes the diaryl
      oxazole based anticancer agent PC-046, which was originally identified for
      development based on selective activity in deleted in pancreas cancer locus 4
      (DPC4/SMAD4) deficient tumors. PC-046 has growth inhibitory activity in a variety
      of tumor types in vitro, and efficacy in SCID mice was shown in human tumor
      xenografts of MV-4-11 acute myeloid leukemia, MM.1S multiple myeloma, and DU-145
      prostate cancer. Pharmacokinetic studies demonstrated relatively high oral
      bioavailability (71%) with distribution to both plasma and bone marrow. No
      myelosuppression was seen in non-tumor bearing SCID mice given a single dose just
      under the acute lethal dose. The COMPARE algorithm in the NCI-60 cell line panel
      demonstrated that PC-046 closely correlated to other known tubulin destabilizing
      agents (correlation coefficients ~0.7 for vincristine and vinblastine). Mechanism
      of action studies showed cell cycle arrest in metaphase and inhibition of tubulin
      polymerization. Overall, these studies show that PC-046 is a synthetically
      derived, small molecule microtubule destabilizing agent. Advantages over existing
      microtubule destabilizing agents include ease of synthesis, lack of MDR cross
      resistance, good oral bioavailability and the lack of acute myelotoxicity.

PMID- 24037083
TI  - Multicenter phase II study of everolimus in patients with metastatic or recurrent
      bone and soft-tissue sarcomas after failure of anthracycline and ifosfamide.
AB  - This multicenter, phase II trial evaluated the efficacy and safety of everolimus,
      an mTOR inhibitor, in patients with metastatic or recurrent bone and soft-tissue
      sarcoma after the failure of anthracycline- and ifosfamide-containing regimens.
      Everolimus was administered orally as 10 mg once daily. The primary endpoint was
      the progression-free rate (PFR) at 16 weeks, assessed by computed tomography scan
      according to RECIST v1.0. Between July 2010 and May 2011, 41 patients were
      enrolled in this study. Among them, 83% received two or more regimens of
      chemotherapy prior to study entry. In 38 patients who the primary endpoint was
      evaluable, 11 patients reached 16 weeks progression-free (one with partial
      response and 10 with stable disease), indicating a PFR at 16 weeks of 27% (95%
      confidence interval [CI], 16-42%). The PFR at 16 weeks was highest in patients
      with angiosarcoma (2 of 3, 67%). With a median follow-up of 10.9 months (range,
      2.3-23.9 months) in living patients, the median progression-free survival was 1.9
      months (95% CI, 1.3-2.4 months) and the median overall survival was 5.8 months
      (95% CI, 3.6-8.0 months). Most adverse events were generally mild and tolerable.
      Grade 3/4 toxicities included hyperglycemia (15%), stomatitis (7%), pain (5%),
      and asthenia (5%). Everolimus shows modest antitumor activity with manageable
      toxicities in heavily pretreated patients with bone and soft-tissue sarcoma.

PMID- 24037084
TI  - Subcutaneous fat pads on body MRI--an early sign of congenital disorder of
      glycosylation PMM2-CDG (CDG1a).
AB  - Infants with phosphomannomutase 2 - congenital disorder of glycosylation (PMM2
      CDG), formerly known as CDG1a, present with failure to thrive, visceral
      dysfunction, thromboembolic events and developmental delays noted before 6 months
      of age. Diagnosis is often delayed due to the considerable variability in
      phenotype. Characteristic, but not universal, features include inverted nipples
      and abnormal subcutaneous fat pads. Neuroimaging performed in the first 4 months
      of life may be normal, although cerebellar and brainstem atrophy is usual after 3
      months of age. Cerebellar and brainstem atrophy have been noted as early as 11
      days of life. We present an infant whose typical subcutaneous and retroperitoneal
      fat deposits were clinically occult, but identified on body MRI. 

PMID- 24037085
TI  - Renal sonography with Doppler for detecting suspected pediatric renin-mediated
      hypertension - is it adequate?
AB  - BACKGROUND: Renal Doppler US is used to evaluate suspected vascular causes of
      hypertension in children, despite mostly unknown diagnostic performance
      characteristics. OBJECTIVE: To evaluate renal Doppler US for detecting vascular
      causes of hypertension in children with high clinical suspicion of aortic or
      renal artery narrowing. MATERIALS AND METHODS: We identified pediatric renal
      Doppler US examinations performed for hypertension between January 1995 and June
      2010 at our institution. We excluded children without follow-up angiography (CT-,
      MR-, or catheter-based). Two pediatric radiologists reviewed imaging studies and
      documented relevant findings. Intrarenal spectral Doppler resistive index
      measurement <0.5 or tardus parvus waveform constituted a positive examination.
      RESULTS: Thirty-five boys and 13 girls underwent renal Doppler US and
      confirmatory imaging (mean age  =  9.0 years). Nineteen US examinations were
      truly negative, two were falsely negative, 18 were truly positive (16 involved
      narrowing of the aorta or main renal artery) and nine were falsely positive.
      Sonography had a sensitivity and specificity of 90% and 68%, respectively, for
      detecting a vascular cause of hypertension. CONCLUSION: Renal Doppler sonography
      reliably detects renin-mediated hypertension caused by aortic or main renal
      artery narrowing in children. More studies are needed to determine its ability to
      detect intrarenal and accessory renal artery stenoses.

PMID- 24037086
TI  - An enhanced security solution for electronic medical records based on AES hybrid
      technique with SOAP/XML and SHA-1.
AB  - This study aims to provide security solutions for implementing electronic medical
      records (EMRs). E-Health organizations could utilize the proposed method and
      implement recommended solutions in medical/health systems. Majority of the
      required security features of EMRs were noted. The methods used were tested
      against each of these security features. In implementing the system, the
      combination that satisfied all of the security features of EMRs was selected.
      Secure implementation and management of EMRs facilitate the safeguarding of the
      confidentiality, integrity, and availability of e-health organization systems.
      Health practitioners, patients, and visitors can use the information system
      facilities safely and with confidence anytime and anywhere. After critically
      reviewing security and data transmission methods, a new hybrid method was
      proposed to be implemented on EMR systems. This method will enhance the
      robustness, security, and integration of EMR systems. The hybrid of simple object
      access protocol/extensible markup language (XML) with advanced encryption
      standard and secure hash algorithm version 1 has achieved the security
      requirements of an EMR system with the capability of integrating with other
      systems through the design of XML messages. 

PMID- 24037087
TI  - Txnip contributes to impaired glucose tolerance by upregulating the expression of
      genes involved in hepatic gluconeogenesis in mice.
AB  - AIMS/HYPOTHESIS: Thioredoxin-interacting protein (TXNIP) is upregulated in the
      hyperglycaemic state and represses glucose uptake, resulting in imbalanced
      glucose homeostasis. In this study, we propose a mechanism of how TXNIP impairs
      hepatic glucose tolerance at the transcriptional level. METHODS: We administered
      adenoviral Txnip (Ad-Txnip) to normal mice and performed intraperitoneal glucose
      tolerance tests (IPGTT), insulin tolerance tests (ITT) and pyruvate tolerance
      tests (PTT). After Ad-Txnip administration, the expression of genes involved in
      glucose metabolism, including G6pc and Gck, was analysed using quantitative real
      time PCR and western blot. To understand the increased G6pc expression in liver
      resulting from Txnip overexpression, we performed pull-down assays for TXNIP and
      small heterodimer partner (SHP). Luciferase reporter assays and chromatin
      immunoprecipitation using the Txnip promoter were performed to elucidate the
      interrelationship between carbohydrate response element-binding protein (ChREBP)
      and transcription factor E3 (TFE3) in the regulation of Txnip expression.
      RESULTS: Overabundance of TXNIP resulted in impaired glucose, insulin and
      pyruvate tolerance in normal mice. Ad-Txnip transduction upregulated G6pc
      expression and caused a decrease in Gck levels in the liver of normal mice and
      primary hepatocytes. TXNIP increased G6pc expression by forming a complex with
      SHP, which is known to be a negative modulator of gluconeogenesis. Txnip
      expression in mouse models of diabetes was decreased by Ad-Tfe3 administration,
      suggesting that TFE3 may play a negative role through competition with ChREBP at
      the E-box of the Txnip promoter. CONCLUSIONS/INTERPRETATION: We demonstrated that
      TXNIP impairs glucose and insulin tolerance in mice by upregulating G6pc through
      interaction with SHP.

PMID- 24037088
TI  - HINCUTs in cancer: hypoxia-induced noncoding ultraconserved transcripts.
AB  - Recent data have linked hypoxia, a classic feature of the tumor microenvironment,
      to the function of specific microRNAs (miRNAs); however, whether hypoxia affects
      other types of noncoding transcripts is currently unknown. Starting from a genome
      wide expression profiling, we demonstrate for the first time a functional link
      between oxygen deprivation and the modulation of long noncoding transcripts from
      ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs).
      Interestingly, several hypoxia-upregulated T-UCRs, henceforth named 'hypoxia
      induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed
      in clinical samples from colon cancer patients. We show that these T-UCRs are
      predominantly nuclear and that the hypoxia-inducible factor (HIF) is at least
      partly responsible for the induction of several members of this group. One
      specific HINCUT, uc.475 (or HINCUT-1) is part of a retained intron of the host
      protein-coding gene, O-linked N-acetylglucosamine transferase, which is
      overexpressed in epithelial cancer types. Consistent with the hypothesis that T
      UCRs have important function in tumor formation, HINCUT-1 supports cell
      proliferation specifically under hypoxic conditions and may be critical for
      optimal O-GlcNAcylation of proteins when oxygen tension is limiting. Our data
      gives a first glimpse of a novel functional hypoxic network comprising protein
      coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category. 

PMID- 24037089
TI  - Dysregulated STAT1-SOCS1 control of JAK2 promotes mammary luminal progenitor cell
      survival and drives ERalpha(+) tumorigenesis.
AB  - We previously reported that STAT1 expression is frequently abrogated in human
      estrogen receptor-alpha-positive (ERalpha(+)) breast cancers and mice lacking
      STAT1 spontaneously develop ERalpha(+) mammary tumors. However, the precise
      mechanism by which STAT1 suppresses mammary gland tumorigenesis has not been
      fully elucidated. Here we show that STAT1-deficient mammary epithelial cells
      (MECs) display persistent prolactin receptor (PrlR) signaling, resulting in
      activation of JAK2, STAT3 and STAT5A/5B, expansion of CD61(+) luminal progenitor
      cells and development of ERalpha(+) mammary tumors. A failure to upregulate
      SOCS1, a STAT1-induced inhibitor of JAK2, leads to unopposed oncogenic PrlR
      signaling in STAT1(-/-) MECs. Prophylactic use of a pharmacological JAK2
      inhibitor restrains the proportion of luminal progenitors and prevents disease
      induction. Systemic inhibition of activated JAK2 induces tumor cell death and
      produces therapeutic regression of pre-existing endocrine-sensitive and
      refractory mammary tumors. Thus, STAT1 suppresses tumor formation in mammary
      glands by preventing the natural developmental function of a growth factor
      signaling pathway from becoming pro-oncogenic. In addition, targeted inhibition
      of JAK2 may have significant therapeutic potential in controlling ERalpha(+)
      breast cancer in humans. 

PMID- 24037090
TI  - Autophagy inhibition radiosensitizes in vitro, yet reduces radioresponses in vivo
      due to deficient immunogenic signalling.
AB  - Clinical oncology heavily relies on the use of radiotherapy, which often leads to
      merely transient responses that are followed by local or distant relapse. The
      molecular mechanisms explaining radioresistance are largely elusive. Here, we
      identified a dual role of autophagy in the response of cancer cells to ionizing
      radiation. On one hand, we observed that the depletion of essential autophagy
      relevant gene products, such as ATG5 and Beclin 1, increased the sensitivity of
      human or mouse cancer cell lines to irradiation, both in vitro (where autophagy
      inhibition increased radiation-induced cell death and decreased clonogenic
      survival) and in vivo, after transplantation of the cell lines into
      immunodeficient mice (where autophagy inhibition potentiated the tumour growth
      inhibitory effect of radiotherapy). On the other hand, when tumour proficient or
      deficient for autophagy were implanted in immunocompetent mice, it turned out
      that defective autophagy reduced the efficacy of radiotherapy. Indeed,
      radiotherapy elicited an anti-cancer immune response that was dependent on
      autophagy-induced ATP release from stressed or dying tumour cells and was
      characterized by dense lymphocyte infiltration of the tumour bed. Intratumoural
      injection of an ecto-ATPase inhibitor restored the immune infiltration of
      autophagy-deficient tumours post radiotherapy and improved the growth-inhibitory
      effect of ionizing irradiation. Altogether, our results reveal that beyond its
      cytoprotective function, autophagy confers immunogenic properties to tumours,
      hence amplifying the efficacy of radiotherapy in an immunocompetent context. This
      has far-reaching implications for the development of pharmacological
      radiosensitizers. 

PMID- 24037091
TI  - B lymphocytes trigger monocyte mobilization and impair heart function after acute
      myocardial infarction.
AB  - Acute myocardial infarction is a severe ischemic disease responsible for heart
      failure and sudden death. Here, we show that after acute myocardial infarction in
      mice, mature B lymphocytes selectively produce Ccl7 and induce Ly6C(hi) monocyte
      mobilization and recruitment to the heart, leading to enhanced tissue injury and
      deterioration of myocardial function. Genetic (Baff receptor deficiency) or
      antibody-mediated (CD20- or Baff-specific antibody) depletion of mature B
      lymphocytes impeded Ccl7 production and monocyte mobilization, limited myocardial
      injury and improved heart function. These effects were recapitulated in mice with
      B cell-selective Ccl7 deficiency. We also show that high circulating
      concentrations of CCL7 and BAFF in patients with acute myocardial infarction
      predict increased risk of death or recurrent myocardial infarction. This work
      identifies a crucial interaction between mature B lymphocytes and monocytes after
      acute myocardial ischemia and identifies new therapeutic targets for acute
      myocardial infarction. 

PMID- 24037092
TI  - Endogenous factor VIII synthesis from the intron 22-inverted F8 locus may
      modulate the immunogenicity of replacement therapy for hemophilia A.
AB  - Neutralizing antibodies (inhibitors) to replacement factor VIII (FVIII, either
      plasma derived or recombinant) impair the effective management of hemophilia A.
      Individuals with hemophilia A due to major deletions of the FVIII gene (F8) lack
      antigenically cross-reactive material in their plasma ("CRM-negative"), and the
      prevalence of inhibitors in these individuals may be as high as 90%. Conversely,
      individuals with hemophilia A caused by F8 missense mutations are CRM-positive,
      and their overall prevalence of inhibitors is <10% (ref. 2). Individuals with the
      F8 intron 22 inversion (found in ~50% of individuals with severe hemophilia A)
      have been grouped with the former on the basis of their genetic defect and CRM
      negative status. However, only ~20% of these individuals develop inhibitors. Here
      we demonstrate that the levels of F8 mRNA and intracellular FVIII protein in B
      lymphoblastoid cells and liver biopsies from individuals with the intron 22
      inversion are comparable to those in healthy controls. These results support the
      hypothesis that most individuals with the intron 22 inversion are tolerized to
      FVIII and thus do not develop inhibitors. Furthermore, we developed a new
      pharmacogenetic algorithm that permits the stratification of inhibitor risk for
      individuals and subpopulations by predicting the immunogenicity of replacement
      FVIII using, as input, the number of putative T cell epitopes in the infused
      protein and the competence of major histocompatibility complex class II molecules
      to present such epitopes. This algorithm showed statistically significant
      accuracy in predicting the presence of inhibitors in 25 unrelated individuals
      with the intron 22 inversion. 

PMID- 24037093
TI  - Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic
      glucose and lipid metabolism and ameliorates diabetes.
AB  - Signaling initiated by hypoxia and insulin powerfully alters cellular metabolism.
      The protein stability of hypoxia-inducible factor-1 alpha (Hif-1alpha) and Hif
      2alpha is regulated by three prolyl hydroxylase domain-containing protein
      isoforms (Phd1, Phd2 and Phd3). Insulin receptor substrate-2 (Irs2) is a critical
      mediator of the anabolic effects of insulin, and its decreased expression
      contributes to the pathophysiology of insulin resistance and diabetes. Although
      Hif regulates many metabolic pathways, it is unknown whether the Phd proteins
      regulate glucose and lipid metabolism in the liver. Here, we show that acute
      deletion of hepatic Phd3, also known as Egln3, improves insulin sensitivity and
      ameliorates diabetes by specifically stabilizing Hif-2alpha, which then increases
      Irs2 transcription and insulin-stimulated Akt activation. Hif-2alpha and Irs2 are
      both necessary for the improved insulin sensitivity, as knockdown of either
      molecule abrogates the beneficial effects of Phd3 knockout on glucose tolerance
      and insulin-stimulated Akt phosphorylation. Augmenting levels of Hif-2alpha
      through various combinations of Phd gene knockouts did not further improve
      hepatic metabolism and only added toxicity. Thus, isoform-specific inhibition of
      Phd3 could be exploited to treat type 2 diabetes without the toxicity that could
      occur with chronic inhibition of multiple Phd isoforms. 

PMID- 24037095
TI  - Reversible photo-controllable gels based on bisthienylethene-doped lecithin
      micelles.
AB  - An aza-15-crown-5-ether functionalized bisthienylethene (BTE-15C5) was
      synthesized, which can reversibly capture and release calcium ions by UV/Vis
      irradiation. After doping this photochromic bisthienylethene with a two-component
      lecithin-Ca(2+) organogel, the original deep-blue gel changed to light-blue fluid
      due to the cooperative binding with Ca(2+) by the open-form bisthienylethene
      dopant. Upon UV irradiation, the closed isomer was formed which released the
      Ca(2+) and the organogel was retrieved. Hence, a novel organic simple doped-type
      three-component photo-induced gel-to-sol transition system was constructed. 

PMID- 24037096
TI  - Upper limb evaluation with robotic exoskeleton. Normative values for indices of
      accuracy, speed and smoothness.
AB  - BACKGROUND: Robotic rehabilitation devices for upper limb function (ULF) provide
      global indicators of a patient's ability, but the temporal evolution of motion
      related to motor control is disregarded. OBJECTIVE: To determine normative values
      for indices of accuracy, speed and smoothness in the evaluation of upper limb
      function. METHODS: Twenty-five healthy individuals performed the Armeo(r)Spring
      device "Vertical Capture" task. Custom stand-alone software was developed to
      provide the following indices: global Hand Path Ratio (HPR), local HPR in the
      target area (locHPR), vertical and horizontal overshoot (vertOS, horOS), maximum
      and mean velocity (maxVel, meanVel), mean/maximum velocity, number of peaks in
      velocity profiles (NVelPeaks) and normalized jerk (NormJerk). The dependence of
      indices on task characteristics was analyzed by an ANCOVA test. Indices inner
      relationships were assessed by a correlation and a factor analysis. Normative
      values were then provided. RESULTS: 4,268 single reaching movements were
      analyzed. Four indices were not affected by movement direction. Indices were
      minimally influenced by the difficulty level. Based upon correlation and factor
      analysis indices and can be grouped into three assessment fields, dealing with
      precision, velocity and smoothness. CONCLUSIONS: We have developed a tool to
      assess ULF in dynamic condition. Normative values were obtained to be used as
      references in assessing patients.

PMID- 24037094
TI  - A liver Hif-2alpha-Irs2 pathway sensitizes hepatic insulin signaling and is
      modulated by Vegf inhibition.
AB  - Insulin initiates diverse hepatic metabolic responses, including gluconeogenic
      suppression and induction of glycogen synthesis and lipogenesis. The liver
      possesses a rich sinusoidal capillary network with a higher degree of hypoxia and
      lower gluconeogenesis in the perivenous zone as compared to the rest of the
      organ. Here, we show that diverse vascular endothelial growth factor (VEGF)
      inhibitors improved glucose tolerance in nondiabetic C57BL/6 and diabetic db/db
      mice, potentiating hepatic insulin signaling with lower gluconeogenic gene
      expression, higher glycogen storage and suppressed hepatic glucose production.
      VEGF inhibition induced hepatic hypoxia through sinusoidal vascular regression
      and sensitized liver insulin signaling through hypoxia-inducible factor-2alpha
      (Hif-2alpha, encoded by Epas1) stabilization. Notably, liver-specific
      constitutive activation of HIF-2alpha, but not HIF-1alpha, was sufficient to
      augment hepatic insulin signaling through direct and indirect induction of
      insulin receptor substrate-2 (Irs2), an essential insulin receptor adaptor
      protein. Further, liver Irs2 was both necessary and sufficient to mediate Hif
      2alpha and Vegf inhibition effects on glucose tolerance and hepatic insulin
      signaling. These results demonstrate an unsuspected intersection between Hif
      2alpha-mediated hypoxic signaling and hepatic insulin action through Irs2
      induction, which can be co-opted by Vegf inhibitors to modulate glucose
      metabolism. These studies also indicate distinct roles in hepatic metabolism for
      Hif-1alpha, which promotes glycolysis, and Hif-2alpha, which suppresses
      gluconeogenesis, and suggest new treatment approaches for type 2 diabetes
      mellitus. 

PMID- 24037098
TI  - An examination of prenatal and postpartum depressive symptoms among women served
      by urban community health centers.
AB  - We characterized depressive symptoms in the prenatal and/or postpartum periods
      and examined associated risk factors among 594 women who received care at
      community health care centers. Women were screened with comprehensive risk
      assessments, which included the Patient Health Questionnaire-9 depression screen,
      during pregnancy and at least 4 weeks after delivery. Fifteen percent had
      depressive symptoms in the prenatal period only; 6 % in the postpartum period
      only, and 8 % had depressive symptoms in both periods. Risk markers varied for
      women who reported depressive symptoms at one period only compared with those who
      reported persistent depressive symptoms. Age (25 years versus younger), having
      experienced abuse, not living with the infant's father, and cigarette smoking
      were associated with depressive symptoms at both periods; being US-born, lacking
      social support, and experiencing food insecurity were associated with reporting
      symptoms only in the prenatal period, and lack of phone access was associated
      with risk only in the postpartum period. Our findings confirm the importance of
      repeated screenings for depressive symptoms during the perinatal period. The
      variability in risk markers associated with periods of reported depressive
      symptoms may reflect their varying associations with persistence, new onset, or
      recovery from depressive symptoms. 

PMID- 24037100
TI  - The effect of barium on perceptions of taste intensity and palatability.
AB  - Barium may affect the perception of taste intensity and palatability. Such
      differences are important considerations in the selection of dysphagia assessment
      strategies and interpretation of results. Eighty healthy women grouped by age
      (younger, older) and genetic taste status (supertaster, nontaster) rated
      intensity and palatability for seven tastants prepared in deionized water with
      and without 40 % w/v barium: noncarbonated and carbonated water, diluted ethanol,
      and high concentrations of citric acid (sour), sodium chloride (salty), caffeine
      (bitter), and sucrose (sweet). Mixed-model analyses explored the effects of
      barium, taster status, and age on perceived taste intensity and acceptability of
      stimuli. Barium was associated with lower taste intensity ratings for sweet,
      salty, and bitter tastants, higher taste intensity in carbonated water, and lower
      palatability in water, sweet, sour, and carbonated water. Older subjects reported
      lower palatability (all barium samples, sour) and higher taste intensity scores
      (ethanol, sweet, sour) compared to younger subjects. Supertasters reported higher
      taste intensity (ethanol, sweet, sour, salty, bitter) and lower palatability
      (ethanol, salty, bitter) than nontasters. Refusal rates were highest for younger
      subjects and supertasters, and for barium (regardless of tastant), bitter, and
      ethanol. Barium suppressed the perceived intensity of some tastes and reduced
      palatability. These effects are more pronounced in older subjects and
      supertasters, but younger supertasters are least likely to tolerate trials of
      barium and strong tastant solutions. 

PMID- 24037101
TI  - Outcomes of a group education/exercise intervention in a population of patients
      with non-specific low back pain: a 3-year review.
AB  - BACKGROUND: Low back pain (LBP) can prove resistant to treatment. Conservative
      management in form of education and exercise is advocated as a first-line
      treatment option. The format of exercise programmes varies, as does the scale of
      improvement. Individual and group models of care are commonly utilised. AIMS: To
      determine the effectiveness of a group education/exercise intervention in a
      cohort of patients with LBP in a teaching hospital in the south east of Ireland.
      In addition, the study explores which factors are predictive of a positive
      outcome. METHODS: Patients aged 18-65 years with LBP > 6 months, who completed
      the programme between January 2008 and December 2010 were included. Outcome
      measures were coded, entered into PASW 18 and cleaned. Pre and post scores were
      analysed with paired t tests and chi (2) analysis. Multiple regression modelling
      was used to determine which baseline variables were independent predictors of
      positive outcome. RESULTS: In total, 668 patients completed the programme. The
      mean age of patients was 45.9 +/- 11.3 years and the majority of patients (69 %)
      were female. Three months post programme, significant improvements in all self
      report and objective physical measures were demonstrated (p < 0.001). Factors
      associated with a positive outcome included lower levels of baseline disability
      and distress, less baseline functional impairment, shorter duration of symptoms
      and not being involved in litigation. CONCLUSION: This group-based
      education/exercise programme proved effective in terms of decreasing pain,
      improving physical function and improving psychosocial status. Identifying
      factors predictive of positive outcome may help maximise patient outcomes.

PMID- 24037102
TI  - The vessels within epithelial circle (VEC) pattern as visualized by magnifying
      endoscopy with narrow-band imaging (ME-NBI) is a useful marker for the diagnosis
      of papillary adenocarcinoma: a case-controlled study.
AB  - BACKGROUND AND AIMS: Pathological studies indicate papillary adenocarcinomas are
      more aggressive than tubular adenocarcinomas, but a definitive diagnosis is
      difficult using conventional endoscopy alone. The vessels within an epithelial
      circle (VEC) pattern, visualized using magnifying endoscopy with narrow-band
      imaging (ME-NBI), may be a feature of papillary adenocarcinoma. The aims of our
      study were to investigate whether the VEC pattern is useful in the preoperative
      diagnosis of papillary adenocarcinoma and to determine whether VEC-positive
      adenocarcinomas are more malignant than VEC-negative lesions. PATIENTS AND
      MATERIALS: From 395 consecutive early gastric cancers resected using the
      endoscopic submucosal dissection method, we analyzed 35 VEC-positive lesions and
      70 VEC-negative control lesions matched for size and macroscopic type. We
      evaluated (1) the correlation between the incidence of VEC-positive cancers and
      the histological papillary structure and (2) differences in the incidence of
      coexisting undifferentiated carcinoma in VEC-positive and VEC-negative cancers
      and the incidence of submucosal and vascular invasion. RESULTS: Histological
      papillary structure was seen in 94 % (33/35) of VEC-positive and 9 % (6/70) of
      VEC-negative cancers, a significant difference (P < 0.001). The incidence of
      coexisting undifferentiated carcinoma was 23 % (8/35) in VEC-positive and 3 %
      (2/70) in VEC-negative cancers (P = 0.002). The incidence of submucosal invasion
      by the carcinoma was 26 % (9/35) in VEC-positive cancers and 10 % (7/70) in VEC
      negative cancers (P = 0.045). CONCLUSIONS: The VEC pattern as visualized using ME
      NBI is a promising preoperative diagnostic marker of papillary adenocarcinoma.
      Coexisting undifferentiated carcinoma and submucosal invasion were each seen in
      approximately one fourth of VEC-positive cancers.

PMID- 24037103
TI  - Hereditary diffuse gastric cancer in a Japanese family with a large deletion
      involving CDH1.
AB  - Hereditary diffuse gastric cancer (HDGC), characterized by susceptibility to
      gastric signet ring cell carcinomas (SRCCs) and caused by CDH1 germline
      mutations, is rare in the Japanese. We present here a Japanese family with HDGC
      identified by comparative genomic hybridization (CGH) analysis. A 55-year-old
      woman was treated with completion gastrectomy for multiple SRCCs, and
      pathological examination revealed approximately 200 foci of SRCC with loss of E
      cadherin expression. Her 30-year-old son had surveillance endoscopy and was found
      to have multiple SRCCs. He underwent total gastrectomy, and 32 foci of SRCC with
      loss of E-cadherin expression were histologically found. Although no point
      mutations were detected in CDH1 by sequencing, CGH revealed a 275-kb deletion
      involving exons 7-16 of CDH1 in both patients. While only a few HDGCs have been
      reported in East Asia, patients with multiple SRCC may need to be offered
      appropriate genetic counseling and testing in this area.

PMID- 24037104
TI  - Interaction of lipophorin with Rhodnius prolixus oocytes: biochemical properties
      and the importance of blood feeding.
AB  - Lipophorin (Lp) is the main haemolymphatic lipoprotein in insects and transports
      lipids between different organs. In adult females, lipophorin delivers lipids to
      growing oocytes. In this study, the interaction of this lipoprotein with the
      ovaries of Rhodnius prolixus was characterised using an oocyte membrane
      preparation and purified radiolabelled Lp (125I-Lp). Lp-specific binding to the
      oocyte membrane reached equilibrium after 40-60 min and when 125I-Lp was
      incubated with increasing amounts of membrane protein, corresponding increases in
      Lp binding were observed. The specific binding of Lp to the membrane preparation
      was a saturable process, with a K(d) of 7.1 +/- 0.9 x 10-8M and a maximal binding
      capacity of 430 +/- 40 ng 125I-Lp/ug of membrane protein. The binding was calcium
      independent and pH sensitive, reaching its maximum at pH 5.2-5.7. Suramin
      inhibited the binding interaction between Lp and the oocyte membranes, which was
      completely abolished at 0.5 mM suramin. The oocyte membrane preparation from R.
      prolixus also showed binding to Lp from Manduca sexta. When Lp was fluorescently
      labelled and injected into vitellogenic females, the level of Lp-oocyte binding
      was much higher in females that were fed whole blood than in those fed blood
      plasma.

PMID- 24037105
TI  - Monitoring resistance to Bacillus thuringiensis subsp. israelensis in the field
      by performing bioassays with each Cry toxin separately.
AB  - Bacillus thuringiensis subsp. israelensis (Bti) is increasingly used worldwide
      for mosquito control and is the only larvicide used in the French Rhone-Alpes
      region since decades. The artificial selection of mosquitoes with field
      persistent Bti collected in breeding sites from this region led to a moderate
      level of resistance to Bti, but to relatively high levels of resistance to
      individual Bti Cry toxins. Based on this observation, we developed a bioassay
      procedure using each Bti Cry toxin separately to detect cryptic Bti-resistance
      evolving in field mosquito populations. Although no resistance to Bti was
      detected in none of the three mosquito species tested (Aedes rusticus, Aedes
      sticticus and Aedes vexans), an increased tolerance to Cry4Aa (3.5-fold) and
      Cry11Aa toxins (8-fold) was found in one Ae. sticticus population compared to
      other populations of the same species, suggesting that resistance to Bti may be
      arising in this population. This study confirms previous works showing a lack of
      Bti resistance in field mosquito populations treated for decades with this
      bioinsecticide. It also provides a first panorama of their susceptibility status
      to individual Bti Cry toxins. In combination with bioassays with Bti, bioassays
      with separate Cry toxins allow a more sensitive monitoring of Bti-resistance in
      the field. 

PMID- 24037106
TI  - Imatinib activity on Schistosoma mansoni.
AB  - Imatinib, a drug used for treatment of human chronic myeloid leukaemia, due to
      its activity against protein kinases, has been also evaluated in vitro against
      Schistosoma mansoni showing high schistosomicidal activity. In the present
      experiments imatinib activity in vitro was confirmed at the doses of 25 uM, 50 uM
      and 100 uM. The first drug activity observed with the lower dose was interruption
      of egg-laying and with the higher dosages was the death of the worms. In mice
      infected with S. mansoni no activity was found even with 1,000 mg/kg/day, 500
      mg/kg/day, single oral dose or when administered for three consecutive days. This
      is another example of the difference of results related to in vitro and in vivo
      trials using S. mansoni worms. 

PMID- 24037107
TI  - The identification of two Trypanosoma cruzi I genotypes from domestic and
      sylvatic transmission cycles in Colombia based on a single polymerase chain
      reaction amplification of the spliced-leader intergenic region.
AB  - A single polymerase chain reaction (PCR) reaction targeting the spliced-leader
      intergenic region of Trypanosoma cruzi I was standardised by amplifying a 231 bp
      fragment in domestic (TcIDOM) strains or clones and 450 and 550 bp fragments in
      sylvatic strains or clones. This reaction was validated using 44 blind coded
      samples and 184 non-coded T. cruzi I clones isolated from sylvatic triatomines
      and the correspondence between the amplified fragments and their domestic or
      sylvatic origin was determined. Six of the nine strains isolated from acute cases
      suspected of oral infection had the sylvatic T. cruzi I profile. These results
      confirmed that the sylvatic T. cruzi I genotype is linked to cases of oral Chagas
      disease in Colombia. We therefore propose the use of this novel PCR reaction in
      strains or clones previously characterised as T. cruzi I to distinguish
      TcIDOMfrom sylvatic genotypes in studies of transmission dynamics, including the
      verification of population selection within hosts or detection of the frequency
      of mixed infections by both T. cruzi I genotypes in Colombia. 

PMID- 24037109
TI  - A serological, parasitological and clinical evaluation of untreated Chagas
      disease patients and those treated with benznidazole before and thirteen years
      after intervention.
AB  - The etiological treatment of Chagas disease is recommended for all patients with
      acute or recent chronic infection, but controversies remain regarding the benefit
      of chemotherapy and interpretations of the parasitological cure after etiological
      treatment. This study compares the laboratory and clinical evaluations of Chagas
      disease patients who were diagnosed 13 years earlier. Fifty-eight Chagas disease
      patients (29 treated with benznidazole and 29 untreated) were matched at the time
      of treatment based on several variables. Conventional serology revealed the
      absence of seroconversion in all patients. However, lower serological titres were
      verified in the treated group, primarily among patients who had the indeterminate
      form of the disease. Haemoculture performed 13 years after the intervention was
      positive for 6.9% and 27.6% of the treated and untreated patients, respectively.
      Polymerase chain reaction tests were positive for 44.8% and 13.8% of the treated
      and untreated patients, respectively. Patients who presented with the
      indeterminate form of the disease at the beginning of the study exhibited less
      clinical progression (17.4%) compared with the untreated group (56.5%).
      Therefore, this global analysis revealed that etiological treatment with
      benznidazole may benefit patients with respect to the clinical progression of
      Chagas disease and the prognosis, particularly when administered to patients with
      the indeterminate form of the disease. 

PMID- 24037110
TI  - Serologic survey of West Nile virus in horses from Central-West, Northeast and
      Southeast Brazil.
AB  - Since the emergence of West Nile virus (WNV) in North America in 1999, there have
      been several reports of WNV activity in Central and South American countries. To
      detect WNV in Brazil, we performed a serological survey of horses from different
      regions of Brazil using recombinant peptides from domain III of WNV. Positive
      samples were validated with the neutralisation test. Our results showed that of
      79 ELISA-positive horses, nine expressed WNV-specific neutralising antibodies.
      Eight of the infected horses were from the state of Mato Grosso do Sul and one
      was from the state of Paraiba. Our results provide additional evidence for the
      emergence of WNV in Brazil and for its circulation in multiple regions of the
      country.

PMID- 24037111
TI  - Prevalence of plasmid-mediated quinolone resistance determinants among
      oxyiminocephalosporin-resistant Enterobacteriaceae in Argentina.
AB  - High quinolone resistance rates were observed among oxyiminocephalosporin
      resistant enterobacteria. In the present study, we searched for the prevalence of
      plasmid-mediated quinolone resistance (PMQR) genes within the 55
      oxyiminocephalosporin-resistant enterobacteria collected in a previous survey.
      The main PMQR determinants were aac(6')-Ib-cr and qnrB, which had prevalence
      rates of 42.4% and 33.3%, respectively. The aac(6')-Ib-cr gene was more
      frequently found in CTX-M-15-producing isolates, while qnrB was homogeneously
      distributed among all CTX-M producers.

PMID- 24037115
TI  - Nano-inclusions: a novel approach to tune the thermal conductivity of In2O3.
AB  - Indium oxides such as In2O3 based thermoelectric ceramics exhibit a figure of
      merit ZT ~0.5 above 1000 K, while optimized ZnO based thermoelectrics may reach
      ZT ~0.3 at 1273 K. A way to further optimize the thermoelectric performance is to
      tune the thermal conductivity. In this work, a reduction of the thermal
      conductivity greater than 30% has been observed. Combining thermal conductivity
      measurements, Scanning Electron Microscopy (SEM) images, X-ray Absorption Fine
      structure spectroscopy (XAFS) data and Full Multiple Scattering calculations, we
      associated the phenomenon with an effective scattering of mid- and long
      wavelength phonons by embedded ZnO nano-inclusions in the In2O3 matrix. The
      results suggest a protocol for the synthesis of new heat-designed materials for
      many novel applications, such as high ZT thermoelectrics, thermal crystals, heat
      optics devices, etc.

PMID- 24037114
TI  - Heterologous expression of gentian MYB1R transcription factors suppresses
      anthocyanin pigmentation in tobacco flowers.
AB  - KEY MESSAGE: Single-repeat MYB transcription factors, GtMYB1R1 and GtMYB1R9 ,
      were isolated from gentian. Overexpression of these genes reduced anthocyanin
      accumulation in tobacco flowers, demonstrating their applicability to
      modification of flower color. RNA interference (RNAi) has recently been used to
      successfully modify flower color intensity in several plant species. In most
      floricultural plants, this technique requires prior isolation of target flavonoid
      biosynthetic genes from the same or closely related species. To overcome this
      limitation, we developed a simple and efficient method for reducing floral
      anthocyanin accumulation based on genetic engineering using novel transcription
      factor genes isolated from Japanese gentians. We identified two single-repeat MYB
      genes--GtMYB1R and GtMYB1R9--predominantly expressed in gentian petals.
      Transgenic tobacco plants expressing these genes were produced, and their flowers
      were analyzed for flavonoid components and expression of flavonoid biosynthetic
      genes. Transgenic tobacco plants expressing GtMYB1R1 or GtMYB1R9 exhibited
      significant reductions in floral anthocyanin accumulation, resulting in white
      flowered phenotypes. Expression levels of chalcone isomerase (CHI),
      dihydroflavonol 4-reductase (DFR), and anthocyanidin synthase (ANS) genes were
      preferentially suppressed in these transgenic tobacco flowers. A yeast two-hybrid
      assay demonstrated that both GtMYB1R1 and GtMYB1R9 proteins interacted with the
      GtbHLH1 protein, previously identified as an anthocyanin biosynthesis regulator
      in gentian flowers. In addition, a transient expression assay indicated that
      activation of the gentian GtDFR promoter by the GtMYB3-GtbHLH1 complex was partly
      canceled by addition of GtMYB1R1 or GtMYB1R9. These results suggest that GtMYB1R1
      and GtMYB1R9 act as antagonistic transcription factors of anthocyanin
      biosynthesis in gentian flowers. These genes should consequently be useful for
      manipulating anthocyanin accumulation via genetic engineering in flowers of other
      floricultural plant species.

PMID- 24037116
TI  - Reconsidering the denominator of the attributable proportion for interaction.

PMID- 24037118
TI  - Factors associated with remission of eczema in children: a population-based
      follow-up study.
AB  - The aim of this study was to analyse factors associated with remission of atopic
      dermatitis (AD) in childhood. A population-based AD cohort of 894 children aged 1
      3 years from a cross-sectional baseline study in 2000 was followed up in 2005.
      The association between remission, background, health, lifestyle, and
      environmental variables was estimated with crude and multivariable logistic
      regression. At follow-up, 52% of the children had remission. Independent factors
      at baseline predicting remission were: milder eczema (adjusted odds ratio (aOR),
      1.43; 95% confidence interval (95% CI) 1.16-1.77); later onset of eczema (aOR
      1.40; 95% CI 1.08-1.80); non-flexural eczema (aOR 2.57; 95% CI 1.62-4.09); no
      food allergy (aOR 1.51; 95% CI 1.11-2.04), and rural living (aOR 1.48; 95% CI
      1.07-2.05). Certain aspects of AD and rural living were important for remission,
      but despite the initial hypotheses to the contrary, the environmental factors
      examined in this paper were not substantial predictors of remission. 

PMID- 24037117
TI  - Quantifying the contributions of behavioral and biological risk factors to
      socioeconomic disparities in coronary heart disease incidence: the MORGEN study.
AB  - Quantifying the impact of different modifiable behavioral and biological risk
      factors on socioeconomic disparities in coronary heart disease (CHD) may help
      inform targeted, population-specific strategies to reduce the unequal
      distribution of the disease. Previous studies have used analytic approaches that
      limit our ability to disentangle the relative contributions of these risk factors
      to CHD disparities. The goal of this study was to assess mediation of the effect
      of low education on incident CHD by multiple risk factors simultaneously.
      Analyses are based on 15,067 participants of the Dutch Monitoring Project on Risk
      Factors for Chronic Diseases aged 20-65 years examined 1994-1997 and followed for
      events until January 1, 2008. Path analysis was used to quantify and test
      mediation of the low education-CHD association by behavioral (current cigarette
      smoking, heavy alcohol use, poor diet, and physical inactivity) and biological
      (obesity, hypertension, diabetes, and hypercholesterolemia) risk factors.
      Behavioral and biological risk factors accounted for 56.6 % (95 % CI 42.6-70.8 %)
      of the low education-incident CHD association. Smoking was the strongest
      mediator, accounting for 27.3 % (95 % CI 17.7-37.4 %) of the association,
      followed by obesity (10.2 %; 95 % CI 4.5-16.1 %), physical inactivity (6.3 %; 95
      % CI 2.7-10.0 %), and hypertension (5.3 %; 95 % CI: 2.8-8.0 %). In summary, in a
      Dutch cohort, the majority of the relationship between low education and incident
      CHD was mediated by traditional behavioral and biological risk factors.
      Addressing barriers to smoking cessation, blood pressure and weight management,
      and physical activity may be the most effective approaches to eliminating
      socioeconomic inequalities in CHD. 

PMID- 24037119
TI  - A case of 5-FU-related severe toxicity associated with the p.Y186C DPYD variant.

PMID- 24037120
TI  - Fast calculation of the infrared spectra of large biomolecules.
AB  - Vibrational spectra of proteins potentially give insight into biologically
      significant molecular motion and the proportions of different types of secondary
      structure. Vibrational spectra can be calculated either from normal modes
      obtained by diagonalizing the mass-weighted Hessian or from the time
      autocorrelation function derived from molecular dynamics trajectories. The
      Hessian matrix is calculated from force fields because it is not practical to
      calculate the Hessian from quantum mechanics for large molecules. As an
      alternative to molecular dynamics the spectral response can be calculated from a
      time autocorrelation derived from numerical solution of the harmonic equations of
      motion, resulting in calculations at least 4 times faster. Because the
      calculation also scales linearly with number of atoms, N, it is faster than
      normal-mode calculations that scale as N (3) for proteins with more then 4,700
      atoms. Using this method it is practical to perform all-atom calculations for
      large biological systems, for example viral capsids, with the order of 10(5)
      atoms. 

PMID- 24037121
TI  - Flexible electronics: Sophisticated skin.

PMID- 24037123
TI  - Synthetically useful noncatalytic strategy: a stereocontrolled rapid cyclization
      of a three component system to afford hexahydropyrrolizines.
AB  - We demonstrate a highly regio- and stereoselective annulation strategy involving
      unprecedented C2-H and N-H of proline esters, alpha,beta-unsaturated aromatic
      aldehydes and deactivated olefins without a catalytic aid to afford medicinally
      important pyrrolo[3,4-a]pyrrolizines and hexahydropyrrolizines under benign
      reaction conditions. 

PMID- 24037122
TI  - Ultrathin conformal devices for precise and continuous thermal characterization
      of human skin.
AB  - Precision thermometry of the skin can, together with other measurements, provide
      clinically relevant information about cardiovascular health, cognitive state,
      malignancy and many other important aspects of human physiology. Here, we
      introduce an ultrathin, compliant skin-like sensor/actuator technology that can
      pliably laminate onto the epidermis to provide continuous, accurate thermal
      characterizations that are unavailable with other methods. Examples include non
      invasive spatial mapping of skin temperature with millikelvin precision, and
      simultaneous quantitative assessment of tissue thermal conductivity. Such devices
      can also be implemented in ways that reveal the time-dynamic influence of blood
      flow and perfusion on these properties. Experimental and theoretical studies
      establish the underlying principles of operation, and define engineering
      guidelines for device design. Evaluation of subtle variations in skin temperature
      associated with mental activity, physical stimulation and
      vasoconstriction/dilation along with accurate determination of skin hydration
      through measurements of thermal conductivity represent some important operational
      examples. 

PMID- 24037124
TI  - Maternal obesity is an independent risk factor for spontaneous extremely preterm
      delivery.

PMID- 24037125
TI  - Control of urinary bladder smooth muscle excitability by the TRPM4 channel
      modulator 9-phenanthrol.
AB  - The Ca (2+)-activated monovalent cation selective transient receptor potential
      melastatin 4 (TRPM4) channel has been recently identified in detrusor smooth
      muscle (DSM) of the urinary bladder. Two recent publications by our research
      group provide evidence in support of the novel hypothesis that TRPM4 channels
      enhance DSM excitability and contractility. This is a critical question as prior
      studies have primarily targeted hyperpolarizing currents facilitated by K(+)
      channels, but the depolarizing component in DSM cells is not well understood. For
      the first time, we utilized the selective TRPM4 channel inhibitor, 9-phenanthrol,
      to investigate TRPM4 channel functional effects in DSM at both cellular and
      tissue levels in rodents. Our new data presented here showed that in rat DSM
      cells, 9-phenanthrol attenuates spontaneous inward currents in the presence of
      the muscarinic receptor agonist, carbachol, thus reducing DSM cell excitability.
      In support of our original hypothesis, we found that TRPM4 channel mRNA levels
      are much higher in DSM vs. vascular smooth muscle and that inhibition of TRPM4
      channels can potentially attenuate DSM excitability. Thus, we postulate the novel
      concept that selective pharmacological inhibition of TRPM4 channels can limit
      both excitability and contractility of DSM. 

PMID- 24037126
TI  - Cross-Talk opposing view: peripheral and central chemoreflexes have additive
      effects on ventilation in humans.

PMID- 24037127
TI  - CrossTalk opposing view: peripheral and central chemoreceptors have hypoadditive
      effects on respiratory motor output.

PMID- 24037128
TI  - CrossTalk opposing view: peripheral and central chemoreceptors have hyperadditive
      effects on respiratory motor control.

PMID- 24037129
TI  - Rebuttal from James Duffin and Jason H. Mateika.

PMID- 24037130
TI  - Rebuttal by Richard J. A. Wilson and Trevor A. Day.

PMID- 24037131
TI  - Rebuttal from Luc J. Teppema and Curtis A. Smith.

PMID- 24037132
TI  - May the Force move you: TSC-ing the mechanical activation of mTOR.

PMID- 24037133
TI  - Remembering those 'lazy' days--imprinting memory in our satellite cells.

PMID- 24037134
TI  - The gold standard for interpretation of slow wave frequency in in vitro and in
      vivo recordings by extracellular electrodes.

PMID- 24037135
TI  - Alpha males: muscle sympathetic discharge on beat-to-beat forearm vascular
      conductance.

PMID- 24037136
TI  - Muscle metabolism and fatigue--in memory of Eric Hultman (10 October 1925-9 March
      2011).

PMID- 24037137
TI  - Activation of quadriceps femoris including vastus intermedius during fatiguing
      dynamic knee extensions.
AB  - PURPOSE: Fatigue-related muscle activity in the superficial quadriceps femoris
      (QF) muscles has been widely examined; however, there is no information on the
      activity of the deep vastus intermedius (VI) muscle during fatiguing dynamic knee
      extensions. The purpose of this study was to investigate neuromuscular activation
      patterns of the QF synergists, including the VI, during fatiguing dynamic knee
      extensions at two submaximal loads. METHODS: Nine healthy men performed dynamic
      knee extensions with loads of 50 and 70 % of one-repetition maximum (1RM) until
      failure. Muscle activation of the VI, vastus lateralis, vastus medialis (VM) and
      rectus femoris was recorded using surface electrodes. Root mean square (RMS)
      amplitude was calculated during the concentric (CON) and eccentric (ECC) phases
      of each repetition, and normalized to the RMS amplitude during the CON and ECC
      phases of the 1RM. Each CON and ECC phase was further divided into three
      subphases according to knee joint angle. RESULTS: The normalized RMS amplitude of
      the four individual QF muscles during the CON phase linearly increased with
      fatigue with contractions at both 50 and 70 % 1RM. The highest RMS amplitude was
      found in VI at flexed knee joint angles until fatigue. This activation pattern
      was more prominent at 70 % 1RM than 50 % 1RM. The RMS amplitude of VM at extended
      knee joint angles was selectively higher at 70 % 1RM than 50 % 1RM. CONCLUSIONS:
      These results suggest that the contribution of the four individual QF muscles to
      fatiguing dynamic knee extensions differs according to knee joint angle and
      intensity of load.

PMID- 24037138
TI  - Designing an intelligent health monitoring system and exploring user acceptance
      for the elderly.
AB  - Recently, many healthcare or health monitoring systems are proposed to improve
      life quality of the elderly in the aging process. The elderly are generally with
      poor health and low information literacy. Low information literacy might be an
      obstacle of using such systems. This research considered the characteristics and
      the needs of the elderly and developed an intelligent health monitoring system
      for the elderly with low information literacy living in the nursing home. The
      system is intelligent since it can monitor the health status of the elderly based
      on clinical and medical knowledge, provide an easy-to-understand and easy-to-use
      user interface for the elderly, and automatically send important or emergency
      feedback to caregivers. Finally, we explored the user acceptance for the elderly
      using our proposed system based on the unified theory of acceptance and user of
      technology model. The experimental results indicate the developed system is
      highly accepted by the elderly in terms of performance expectation, endeavor
      expectation, social influence, and facilitating condition. 

PMID- 24037139
TI  - Classification of imperfectly time-locked image RSVP events with EEG device.
AB  - Classification based on EEG data in an RSVP experiment is considered. Although
      the latency in neural response relative to the stimulus onset time may be more
      realistically considered to vary across trials due to factors such as subject
      fatigue and environmental distractions, it is nevertheless assumed to be time
      locked to the stimulus in most of the existing work as a means to alleviate the
      computational complexity. We consider here a more practical scenario that allows
      variation in response latency and develop a rigorous statistical formulation for
      modeling the uncertainty within the varying latency coupled with a likelihood
      ratio test (LRT) for classification. The new model not only improves the EEG
      classification performance, but also may predict the true stimulus onset time
      when this information is not precisely available. We test the proposed LRT
      algorithm on an EEG data set from an image RSVP experiment and show that, by
      admitting the latency variation, the proposed approach consistently outperforms a
      method that relies on perfect time-locking (AUC: 0.88 vs 0.86), especially when
      the stimulus onset time is not precisely available (AUC: 0.84 vs 0.71).
      Furthermore, the predicted stimulus onset times are highly enriched around the
      true onset time with p-value = 5.2 x 10(44).

PMID- 24037141
TI  - Antimicrobial resistance monitoring in Neisseria gonorrhoeae and strategic use of
      funds from the Global Fund to set up a systematic Moroccan gonococcal
      antimicrobial surveillance programme.
AB  - OBJECTIVES: The aims of this study were to assess antimicrobial resistance in
      Neisseria gonorrhoeae infections and update the treatment in the national
      guidelines for the syndromic management of sexually transmitted infections in
      Morocco. METHODS: 171 men complaining of urethral discharge were recruited from
      basic health services during 2009. Urethral swab samples were collected and N
      gonorrhoeae identification was performed by culture. Antimicrobial susceptibility
      testing was performed using the Etest method and the antimicrobial agents tested
      were ciprofloxacin, penicillin, spectinomycin, tetracycline, ceftriaxone and
      cefixime. RESULTS: A total of 72 isolates were examined. Significant resistance
      to tetracycline (92.8%) and ciprofloxacin (86.8%), which was used as first-line
      treatment in gonococcal infections, was noted. No resistance to spectinomycin,
      ceftriaxone or cefixime was detected in all the isolates. CONCLUSIONS: Following
      these results the Ministry of Health of Morocco replaced ciprofloxacin and
      introduced ceftriaxone 250 mg as a single dose in the treatment of gonococcal
      infections. Using funds from the Global Fund to Fight AIDS, Tuberculosis and
      Malaria (the Global Fund), a surveillance programme was set up for antimicrobial
      resistance testing in N gonorrhoeae.

PMID- 24037142
TI  - Lipids and the endothelium: bidirectional interactions.
AB  - The endothelium is often viewed solely as the barrier that prevents the
      penetration of circulating lipoproteins into the arterial wall. However, recent
      research has demonstrated that the endothelium has an important part in
      regulating circulating fatty acids and lipoproteins, and is in turn affected by
      these lipids/lipoproteins in ways that appear to have important repercussions for
      atherosclerosis. Thus, a number of potentially toxic lipids are produced during
      lipolysis of lipoproteins at the endothelial cell surface. Catabolism of
      triglyceride-rich lipoproteins creates free fatty acids that are readily taken up
      by endothelial cells, and, likely through the action of acyl-CoA synthetases,
      exacerbate inflammatory processes. In this article, we review how the endothelium
      participates in lipoprotein metabolism, how lipids alter endothelial functions,
      and how lipids are internalized, processed, and transported into the
      subendothelial space. Finally, we address the many endothelial changes that might
      promote atherogenesis, especially in the setting of diabetes. 

PMID- 24037144
TI  - An unusual case of hypercalcemia in a patient with renal insufficiency.

PMID- 24037143
TI  - Increasing frequency of acute kidney injury amongst children hospitalized with
      nephrotic syndrome.
AB  - BACKGROUND: Nephrotic syndrome (NS) is among the most common kidney diseases seen
      in children. The major complications of NS include infection, acute kidney injury
      (AKI), and thromboembolism (TE). The objective of this study was to analyze long
      term trends in the epidemiology of major complications of pediatric NS. METHODS:
      We used the Healthcare Cost and Utilization Project Kids' Inpatient Database for
      the years 2000-2009 to perform an analysis of U.S. hospitalizations of children
      diagnosed with NS with or without infection, AKI or TE. RESULTS: The frequency of
      NS hospitalizations complicated by AKI increased by 158 % between 2000 and 2009
      (p < 0.001). The frequency of NS hospitalizations with infection and TE remained
      stable overall. Pneumonia was the most common infectious complication while
      peritonitis decreased by 50 % (p < 0.001). Importantly, development of any of
      these major complications of NS resulted in ~2-3-fold increases in both hospital
      charges and length of stay. CONCLUSIONS: It is concerning that the frequency of
      AKI in children hospitalized with NS has more than doubled in the past decade.
      Strategies to prevent or initiate earlier treatments for complications of NS
      could have a major impact on both morbidity and health care expenses.

PMID- 24037146
TI  - Treatment of wastewater contaminated with detergents and mineral oils using
      effective and scalable technology.
AB  - In this work, effective, cheap and scalable methodology is introduced to treat
      oily wastewater. The water produced from car-wash processes was utilized as a
      model because it has various pollutants - oil, lubricants, detergents, solid
      particles, etc. The results showed that the turbidity and chemical oxygen demand
      (COD) values dramatically decrease by using the proposed treatment process, which
      consists of coagulation, flocculation, sand filtration, and oxidation followed by
      sand as well as activated carbon filtration. Moreover, the operating conditions
      were optimized. Without adjustment of the pH value of car-wash wastewater, it was
      found that 200 ppm of ferric chloride, as a coagulant, and 1 ppm of potassium
      permanganate, as an oxidant, are the optimum doses. The COD and turbidity values
      of the final treated wastewater were reduced by almost 88 and 100%, respectively.
      A prototype with 15 L capacity was designed and fabricated to investigate the
      scaling up and continuity of the proposed treatment strategy. The results were
      very promising and indicated that the introduced methodology can be industrially
      applied. 

PMID- 24037145
TI  - Cost-effective solutions for water quality improvement in the Dommel River
      supported by sewer-WWTP-river integrated modelling.
AB  - This project aims at finding cost-efficient sets of measures to meet the Water
      Framework Directive (WFD) derived goals for the Dommel River (The Netherlands).
      Within the project, both acute and long-term impacts of the urban wastewater
      system on the chemical and ecological quality of the river are studied with a
      monitoring campaign in the urban wastewater system (wastewater treatment plant
      and sewers) and in the receiving surface water system. An integrated model, which
      proved to be a powerful tool to analyse the interactions within the integrated
      urban wastewater system, was first used to evaluate measures in the urban
      wastewater system using the existing infrastructure and new real-time control
      strategies. As the latter resulted to be beneficial but not sufficient, this
      paper investigated the use of additional infrastructural measures to improve the
      system cost-effectively and have it meet the Directive's goals. Finally, an
      uncertainty analysis was conducted to investigate the impact of uncertainty in
      the main model assumptions and model parameters on the performance robustness of
      the selected set of measures. Apart from some extreme worst-case scenarios, the
      proposed set of measures turned out to be sufficiently robust. Due to the
      substantial savings obtained with the results of this project, the pay-back time
      of the whole monitoring and modelling work proved to be less than 5 months. This
      illustrates the power of mathematical modelling for decision support in the
      context of complex urban water systems. 

PMID- 24037147
TI  - Biological phosphorus and nitrogen removal in sequencing batch reactors: effects
      of cycle length, dissolved oxygen concentration and influent particulate matter.
AB  - Removal of phosphorus (P) and nitrogen (N) from municipal wastewaters is required
      to mitigate eutrophication of receiving water bodies. While most treatment plants
      achieve good N removal using influent carbon (C), the use of influent C to
      facilitate enhanced biological phosphorus removal (EBPR) is poorly explored. A
      number of operational parameters can facilitate optimum use of influent C and
      this study investigated the effects of cycle length, dissolved oxygen (DO)
      concentration during aerobic period and influent solids on biological P and N
      removal in sequencing batch reactors (SRBs) using municipal wastewaters.
      Increasing cycle length from 3 to 6 h increased P removal efficiency, which was
      attributed to larger portion of N being removed via nitrite pathway and more
      biodegradable organic C becoming available for EBPR. Further increasing cycle
      length from 6 to 8 h decreased P removal efficiencies as the demand for
      biodegradable organic C for denitrification increased as a result of complete
      nitrification. Decreasing DO concentration in the aerobic period from 2 to 0.8 mg
      L(-1) increased P removal efficiency but decreased nitrification rates possibly
      due to oxygen limitation. Further, sedimented wastewater was proved to be a
      better influent stream than non-sedimented wastewater possibility due to the
      detrimental effect of particulate matter on biological nutrient removal. 

PMID- 24037148
TI  - Sorption and degradation of wastewater-associated pharmaceuticals and personal
      care products in agricultural soils and sediment.
AB  - Pharmaceuticals and personal care products (PPCPs) have drawn popular concerns
      recently as an emerging class of aquatic contaminants. In this study, adsorption
      and degradation of four selected PPCPs, metronidazole, tinidazole, caffeine and
      chloramphenicol, have been investigated in the laboratory using two agricultural
      soils in China and sediment from Changjiang River. Adsorption tests using a batch
      equilibrium method demonstrated that adsorption of all tested chemicals in soils
      could be well described with Freundlich equation, and their adsorption affinity
      on soil followed the order of chloramphenicol > caffeine > tinidazole >
      metronidazole. Generally, higher Kf value was associated with soils which had
      higher organic matter contents (except for caffeine acid in this study).
      Degradation of selected PPCPs in soils generally followed first-order exponential
      decay kinetics, and half-lives ranging from 0.97 to 10.21 d. Sterilization
      generally decreased the degradation rates, indicating that microbial activity
      played a significant role in the degradation in soils. The degradation rate
      constant decreased with increasing initial chemical concentrations in soil,
      implying that the microbial activity was inhibited with high chemical loading
      levels. 

PMID- 24037149
TI  - Photoelectrocatalytic study and scaling up of titanium dioxide electrodes for
      wastewater treatment.
AB  - Different TiO2 photoelectrodes have been characterized and tested for the
      photoelectrocatalytic oxidation of methanol. Particulate electrodes (TiO2/Ti and
      TiO2/ITO) have been shown to notably favour charge-carrier transfer at the
      electrolyte interface while a thermal electrode (Ti) has been shown to favour
      charge-carrier separation when applying an electric potential bias according to
      cyclic voltammetry technique, as a consequence of differences in TiO2 surface
      between particulate and thermal electrodes. Particulate electrodes lead to a
      higher photoelectrocatalytic activity for methanol oxidation compared to that of
      the thermal electrode, probably due to the pure-rutile TiO2 phase composition of
      the latter and its lower surface area. TiO2/Ti electrode has been shown to be the
      most effective photoelectrode tested for methanol oxidation since its activity
      was improved by the combination of the particulate TiO2 layer and the high
      electrical conductivity of the support. Generally, photocurrent density measured
      in the photoelectrochemical cell seems to correlate with activity, whereas this
      correlation is not observed when using a larger photoelectrocatalytic reactor. In
      contrast, the activity obtained for the scaled-up electrode is found to be
      similar in terms of surface kinetic constant to that obtained at laboratory
      scale. 

PMID- 24037150
TI  - Survey monitoring results on the reduction of micropollutants, bacteria,
      bacteriophages and TSS in retention soil filters.
AB  - A main source of surface water pollution in Western Europe stems from combined
      sewer overflow. One of the few technologies available to reduce this pollution is
      the retention soil filter. In this research project, we evaluated the cleaning
      efficiency of retention soil filters measuring the concentration ratio of
      standard wastewater parameters and bacteria according to factors limiting
      efficiency, such as long dry phases or phases of long-lasting retention.
      Furthermore, we conducted an initial investigation on how well retention soil
      filters reduce certain micropollutants on large-scale plants. There was little
      precipitation during the 1-year sampling phase, which led to fewer samples than
      expected. Nevertheless, we could verify how efficiently retention soil filters
      clean total suspended solids. Our results show that retention soil filters are
      not only able to eliminate bacteria, but also to retain some of the
      micropollutants investigated here. As the filters were able to reduce diclofenac,
      bisphenol A and metoprolol by a median rate of almost 75%, we think that further
      investigations should be made into the reduction processes in the filter. At this
      point, a higher accuracy in the results could be achieved by conducting bench
      scale experiments. 

PMID- 24037151
TI  - Modeling the die-off of E. coli and Ascaris in wastewater-irrigated vegetables:
      implications for microbial health risk reduction associated with irrigation
      cessation.
AB  - This study assessed the die-off of Escherichia coli (E. coli) and Ascaris suum on
      lettuce (Great Lakes 118) and cabbage (Brassica oleracea var capitata) in
      wastewater-irrigated fields using comparative mathematical die-off models. The
      study revealed that none of the survival curves of E. coli and A. suum was best
      fitted with the log-linear model, indicating that the classical first-order
      kinetic approach is inadequate in many cases. The biphasic die-off model best
      described the die-off of E. coli on lettuce (kmax1 = 2.62 day(-1) and kmax2 =
      0.22 day(-1)) and cabbage (kmax1 = 1.06 day(-1) and kmax2 = 0.53 day(-1)). The
      die-off of A. suum on lettuce was best described by the biphasic model (kmax1 =
      0.48 day(-1) and kmax2 = 0.01 day(-1)) and best described by log linear + tail
      (kmax = 0.44) on cabbage. A comparative health risk assessment associated with
      the consumption of lettuce showed significant underestimation of the number of
      days of irrigation cessation required to achieve E. coli O157:H7 and Ascaris
      tolerable annual infection risk when using biphasic die-off rates compared with
      other die-off rates. The study stresses the need to test different die-off models
      as inputs for quantitative microbial risk assessment (QMRA) particularly for
      interventions associated with health risk reduction. 

PMID- 24037152
TI  - Advanced monitoring of water systems using in situ measurement stations: data
      validation and fault detection.
AB  - In situ continuous monitoring at high frequency is used to collect water quality
      information about water bodies. However, it is crucial that the collected data be
      evaluated and validated for the appropriate interpretation of the data so as to
      ensure that the monitoring programme is effective. Software tools for data
      quality assessment with a practical orientation are proposed. As water quality
      data often contain redundant information, multivariate methods can be used to
      detect correlations, pertinent information among variables and to identify
      multiple sensor faults. While principal component analysis can be used to reduce
      the dimensionality of the original variable data set, monitoring of some
      statistical metrics and their violation of confidence limits can be used to
      detect faulty or abnormal data and can help the user apply corrective action(s).
      The developed algorithms are illustrated with automated monitoring systems
      installed in an urban river and at the inlet of a wastewater treatment plant. 

PMID- 24037153
TI  - CuO/ZnO coupled oxide films obtained by the electrodeposition technique and their
      photocatalytic activity in phenol degradation under solar irradiation.
AB  - CuO/ZnO coupled oxide films were electrodeposited onto an aluminum substrate and
      tested as photocatalysts in degradation of phenol molecules in aqueous solution
      under sunlight. The obtained films were characterized by X-ray diffraction,
      scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy
      (EDS). The results showed that the photocatalytic activity of films was
      significant, especially to coupled oxide film with a CuO/ZnO ratio equal to
      0.697, which presented about 70% degradation of the aromatic molecules and 42% of
      total organic carbon (TOC) removal at 300 min under solar irradiation. Therefore,
      this work highlights the potential application of CuO/ZnO coupled oxide films
      obtained by electrodeposition onto aluminum substrate in the field of
      photocatalysis. 

PMID- 24037154
TI  - Methodology to elaborate the bathing water profile on urban beaches, according to
      the requirements of the European Directive 2006/7/EC: the case of Santander
      beaches (Spain).
AB  - The approval of the current Bathing Water Directive (Directive 2006/7/EC) set the
      necessity to define the bathing water profile. The goals established in the
      definition of the profile are: (i) to know the processes that determine the
      concentration of bacteriological indicators in the aquatic environment, (ii) to
      obtain relationships between the cause of pollution and its effects, and (iii) to
      evaluate the fulfilment of the Directive and to set the Quality Monitoring and
      Assessment Program, according to the bacteriological characteristics of the
      bathing water. In this paper an approach to elaborate the bathing water profile
      and its application to several bathing waters located in Santander municipality
      (North Spain) is shown. The methodology involves the assessment of advection,
      diffusion and reaction processes of bacteriological organisms in the aquatic
      environment by using mathematical models and the selection of an indicator to
      evaluate the probability to exceed the bacteriological concentrations established
      in Directive 2006/7/EC, which is useful for the 'source apportionment'
      assessment. In the definition of the bathing water profile we have considered the
      sanitation system operating under normal conditions, which includes storm water
      overflows, uncontrolled discharges and the discharge produced when the pumping
      system of the wastewater breaks. Finally, according to the bacteriological
      characteristics of the bathing water it is necessary to develop the Quality
      Monitoring and Assessment, which has been done taking into account the
      requirements established in Directive 2006/7/EC and the uncertainties detected in
      such a method regarding the number of samples to be considered. 

PMID- 24037155
TI  - Removal mechanism of cationic dye (Safranin O) from the aqueous phase by dead
      macro fungus biosorbent.
AB  - Batch biosorption parametric experiments were carried out to delineate the
      removal mechanism of cationic dye, namely, Safranin O, from the aqueous phase
      using biosorbent prepared from wood rotting dead macro fungus 'Fomitopsis
      carnea'. Experimental data of the kinetic experiments at various temperatures
      (19, 27 and 35  degrees C) were well described using pseudo-second order kinetic
      models. Raising temperature from 19 to 35  degrees C enhanced the dye uptake
      potential of the biosorbent from 1,000 to 1,250 mg/g. The other variables studied
      were the effect of common salt (NaCl) and pH on the dye removal potential of the
      biosorbent. Decreased dye removal (%) efficiency at higher salt concentration
      suggests involvement of an ion-exchange type sorption mechanism. The pH study
      revealed that dye removal may occur due to the existence of an electrostatic
      attraction force between negatively charged biosorbent particles and dye cation.
      However desorption using mineral acid (H2SO4 and HCl) exhibited the highest
      desorption up to 76%, followed by organic acid (52%) and distilled water (not
      more than 2%) indicating the possibility of ion-exchange as the dominating dye
      sorption mechanism. Fourier transform infrared (FT-IR) spectroscopy analysis of
      the biosorbent, Safranin O and Safranin O loaded biosorbent also supported the
      possibility of ion-exchange as the dominating mechanism due to the presence of
      major peaks of Safranin O on the IR spectra of Safranin O loaded biosorbent,
      indicating that the Safranin O was present in its unaltered form on the surface
      of the biosorbent. 

PMID- 24037156
TI  - Water, soil and nutrient losses caused by Wenchuan Earthquake: a case study in
      Pengzhou.
AB  - Wenchuan Earthquake triggered a large number of geological hazards, dramatically
      stimulating soil erosion. This study was carried out in Pengzhou County, Sichuan
      Province. By comparison of sediment, runoff and nutrient losses in earthquake
      damaged forests (EF) and unaffected forests (UF), the actual status of soil
      erosion after the Wenchuan Earthquake was investigated by runoff plots. Results
      showed that water and soil losses were dramatically increased after earthquake.
      During the study period (from August to November 2010), UF runoffs were 19.26,
      36.76, 10.68 and 7.51 L m(-2), while total runoffs in EF sites were 30.41, 25.79,
      5.03 and 2.67 L m(-2) respectively, which were 15, 15, 18 and 19 times more than
      those in UF. Total sediment losses in EF sites were 28.94, 25.16, 4.11 and 1.98 t
      km(-2) respectively while in UF they were 707.69, 610.05, 113.43 and 58.95 t km(
      2) respectively during the same study period, i.e. 23, 23, 32 and 29 times more
      than those in UF. Path analysis showed that both vegetation and rainfall exerted
      an indirect influence on sediment loss by significantly influencing runoff, which
      correlated with sediment loss very significantly. Although no obvious differences
      of the nutrients' concentration in runoff water (soluble organic carbon (SOC),
      total nitrogen (TN), total phosphorus (TP) and total potassium (TK)) between EF
      and UF sites were observed, total losses of the four nutrients were significantly
      higher in EF than in UF sites (for example, in EF sites, SOC, TN, TP and TK
      losses were 970.52, 114.46, 2.26 and 307.00 g m(-2) respectively, while in UF
      they were 38.13, 4.22, 0.10 and 13.28 g m(-2)) due to significantly higher runoff
      in EF sites. In conclusion, soil erosion was significantly more serious due to
      the loss of forested lands resulting from the Wenchuan Earthquake, delaying the
      restoring process of forest cover and weakening the ecological linkage between
      upstream and downstream. 

PMID- 24037157
TI  - Model-based monitoring of stormwater runoff quality.
AB  - Monitoring of micropollutants (MP) in stormwater is essential to evaluate the
      impacts of stormwater on the receiving aquatic environment. The aim of this study
      was to investigate how different strategies for monitoring of stormwater quality
      (combining a model with field sampling) affect the information obtained about MP
      discharged from the monitored system. A dynamic stormwater quality model was
      calibrated using MP data collected by automatic volume-proportional sampling and
      passive sampling in a storm drainage system on the outskirts of Copenhagen
      (Denmark) and a 10-year rain series was used to find annual average (AA) and
      maximum event mean concentrations. Use of this model reduced the uncertainty of
      predicted AA concentrations compared to a simple stochastic method based solely
      on data. The predicted AA concentration, obtained by using passive sampler
      measurements (1 month installation) for calibration of the model, resulted in the
      same predicted level but with narrower model prediction bounds than by using
      volume-proportional samples for calibration. This shows that passive sampling
      allows for a better exploitation of the resources allocated for stormwater
      quality monitoring. 

PMID- 24037158
TI  - A study on the migration and transformation law of nitrogen in urine in municipal
      wastewater transportation and treatment.
AB  - Many studies suggest that the total nitrogen (TN) in urine is around 9,000 mg/L
      and about 80% of nitrogen in municipal wastewater comes from urine, because
      nitrogen mainly occurs in the form of urea in fresh human urine. Based on this
      fact, the study on the migration and transformation law of nitrogen in urine and
      its influencing factors was carried out. It can be seen from the experimental
      results that the transformation rate of urea in urine into ammonia nitrogen after
      standing for 20 days is only about 18.2%, but the urea in urine can be hydrolyzed
      into ammonia nitrogen rapidly after it is catalyzed directly with free urease or
      indirectly with microorganism. Adding respectively a certain amount of urease,
      activated sludge and septic-tank sludge to urine samples can make the maximum
      transformation rate achieve 85% after 1 day, 2 days and 6 days, respectively. In
      combination with some corresponding treatment methods, recycling of nitrogen in
      urine can be achieved. The results are of great significance in guiding
      denitrification in municipal wastewater treatment. 

PMID- 24037159
TI  - Cellulose production by Gluconacetobacter kakiaceti GM5 in two batch process
      using vinasse as culture media.
AB  - The present study was conducted to evaluate the cellulose production by
      Gluconacetobacter kakiaceti GM5 by means of two aerobic treatments: the static
      discontinuous fermentation process (treatment 1) and the discontinuous
      fermentation process in a rotary shaker (treatment 2). All these experiments were
      carried out using vinasse as experimental culture media (VM) and were compared
      with standard media containing glucose at 2% (standard medium (SM)). A sample of
      each treatment was extracted every 24 h over a period of 168 h. The maximum rates
      of cellulose produced in treatment 1 using SM added up to 3.63 +/- 0.18 g l(-1),
      and to 4.15 +/- 0.16 g l(-1) when VM was used. The amount of cellulose produced
      in treatment 2 using SM was 2.95 +/- 0.09 g l(-1) (which suggests an increase of
      37%), and added up to 1.84 +/- 0.07 g l(-1) when using VM. A better global yield
      of both treatments in terms of sugar consumption after 168 h was obtained when
      using VM: 32% in treatment 1, whereas in treatment 2 it was 9%. A 20% decrease on
      vinasse COD (Chemical Oxygen Demand) values was found to be yet another important
      advantage of working with this strain. 

PMID- 24037160
TI  - Activated carbon prepared from coffee pulp: potential adsorbent of organic
      contaminants in aqueous solution.
AB  - The processing of coffee beans generates large amounts of solid and liquid
      residues. The solid residues (pulp, husk and parchment) represent a serious
      environmental problem and do not have an adequate disposal mechanism. In this
      work, activated carbons (ACs) for adsorption of organic compounds were prepared
      from coffee pulp by controlled temperature at different pulp/Na2HPO4 ratios (4:1,
      2:1, 5:4 and 1:1). The N2 adsorption/desorption isotherms showed ACs with high
      quantities of mesopores and micropores and specific surface areas of 140, 150,
      450 and 440 m(2)g(-1) for AC 4:1, AC 2:1, AC 5:4 and AC 1:1, respectively. The
      prepared material AC 5:4 showed a higher removal capacity of the organic
      contaminants methylene blue (MB), direct red (DR) and phenol than did a Merck AC.
      The maximum capacities for this AC are approximately 150, 120 and 120 mg g(-1)
      for MB, DR and phenol, respectively. Thus, a good adsorbent was obtained from
      coffee pulp, an abundant Brazilian residue. 

PMID- 24037161
TI  - Removal and transformation of dissolved organic matter (DOM) during the treatment
      of partially stabilized leachate in membrane bioreactor.
AB  - The removal of dissolved organic matter (DOM) during municipal solid waste
      leachate treatment in a membrane bioreactor (MBR) was investigated. The MBR was
      operated with fouled and cleaned membranes, at a time. DOM, mixed liquor, and
      effluent were characterized by fractionation and fluorescence excitation-emission
      matrix (EEM) spectroscopy. Results showed DOM removals of 82% during the MBR
      operation with the fouled membrane. The DOM characterization indicated that most
      of the hydrophilic compounds and protein-like substances could be significantly
      removed by microbial activities in the treatment processes. Furthermore partial
      removal or transformation of organic substances was observed during membrane
      filtration. The fouled membrane improved DOM rejection by only about 2% when
      compared to the cleaned membrane, which demonstrated the significance of
      irreversible foulants on DOM rejection. There were insignificant differences in
      DOM fractionation and EEM fluorescence spectra between water samples filtered
      through the fouled and cleaned membranes. 

PMID- 24037162
TI  - Effective growth of dinoflagellate Prorocentrum minimum by cultivating the cells
      using municipal wastewater as nutrient source.
AB  - Several studies have been conducted worldwide in order to develop a more
      economical method for mass algal cultivation so that more cost-effective biomass
      production can be accessed. One of the directions is to reduce production costs
      by using wastewater as a nutrient source in algal cell cultivation. The growth
      ability of a red-tide causative dinoflagellate species, Prorocentrum minimum, in
      various concentrations of local urban wastewater was examined in this study. The
      highest exponential growth rate and maximum cell density (MCD) were achieved when
      autoclaved 10% wastewater was used for cell cultivation, although the cells could
      survive in 0.01-100% wastewater. Both growth rate and MCD of the cells in
      wastewater were found to be substantially higher than that in optimized L1
      culture medium. This research highlights the potential of using wastewater as a
      cost-effective approach for mass cultivation of dinoflagellate cells with
      consequent production of valuable microalgal biomass. 

PMID- 24037163
TI  - Local effects of global climate change on the urban drainage system of Hamburg.
AB  - The Hamburg Water Group owns and operates a sewer network with a total length of
      more than 5,700 km. There has been increasing attention paid to the possible
      impacts of predicted changes in precipitation patterns on the sewer network
      infrastructure. The primary objective of the work presented in this paper is an
      estimation of the hydraulic impacts of climate change on the Hamburg drainage
      system. As a first step, simulated rainfalls based on the regional climate model
      REMO were compared and validated with long-term precipitation measurements. In
      the second step, the hydraulic effects on the sewer network of Hamburg have been
      analyzed based on simulated long-term rainfall series for the period of 2000
      2100. Simulation results show a significant increase in combined sewer overflows
      by 50% as well as an increase in surcharges of storm sewer manholes. However,
      there is still a substantial amount of uncertainty resulting from model
      uncertainty and unknown development of future greenhouse gas emissions. So far,
      there seems to be no sound basis for the implementation of an overall climate
      factor for sewer dimensioning for the Hamburg region. Nevertheless, possible
      effects of climate change should be taken into account within the planning
      process for major sewer extensions or modifications. 

PMID- 24037165
TI  - Modelling of E. coli distribution in coastal areas subjected to combined sewer
      overflows.
AB  - Rivers, lakes and the sea were the natural receivers of raw urban waste and storm
      waters for a long time but the low sustainability of such practice, the increase
      of population and a renewed environmental sensibility increased researcher
      interest in the analysis and mitigation of the impact of urban waters on
      receiving water bodies (RWB). In Europe, the integrated modelling of drainage
      systems and RWB has been promoted as a promising approach for implementing the
      Water Framework Directive. A particular interest is given to the fate of
      pathogens and especially of Escherichia coli, in all the cases in which an
      interaction between population and the RWB is foreseen. The present paper aims to
      propose an integrated water quality model involving the analysis of several sewer
      systems (SS) discharging their polluting overflows on the coast in a sensitive
      marine environment. From a modelling point of view, the proposed application
      integrated one-dimensional drainage system models with a complex three
      dimensional model analysing the propagation in space and time of E. coli in the
      coastal marine area. The integrated approach was tested in a real case study (the
      Acicastello bay in Italy) where data were available both for SS model and for RWB
      propagation model calibration. The analysis shows a good agreement between the
      model and monitored data. The integrated model was demonstrated to be a valuable
      tool for investigating the pollutant propagation and to highlight the most
      impacted areas. 

PMID- 24037164
TI  - Management and treatment of landfill leachate by a system of constructed wetlands
      and ponds in Singapore.
AB  - Lorong Halus, Singapore's first landfill leachate treatment system, consists of a
      pre-treatment system (8,000 m(2)), five constructed reed beds (38,000 m(2)), five
      polishing ponds (13,000 m(2)), an education centre and a learning trail for
      visitors. Eight species of wetland plants (total 160,000 plants) were selected
      for their ability to uptake nutrients, tolerance to low phosphorus concentrations
      and resistance to pest infestations. The wetland was launched in March 2011 and
      water quality monitoring started in April 2011. The removal efficiencies of the
      pre-treatment system from April 2011 to August 2012 are biochemical oxygen demand
      (BOD5) 57.4%; chemical oxygen demand (COD) 23.6%; total suspended solids (TSS)
      55.1%; ammoniacal nitrogen (NH4-N) 76.8%; total phosphorus (TP) 33.3% and total
      nitrogen (TN) 60.2%. Removal efficiencies of the reed beds are BOD5 47.0%; COD
      42.2%; TSS 57.0%; NH4-N 82.5%; TP 29.3% and TN 83.9%. Plant growth is generally
      satisfactory, but the lower than designed volume of leachate has adversely
      affected some sections of plants and resulted in uneven flow distribution in reed
      beds. The plant management programme includes improving plant regrowth by
      harvesting of alternate strips of plants and replanting. The treated effluent
      meets water quality limits for discharge to the public sewer and is subsequently
      treated by the NEWater treatment system, which recycles water for industrial and
      indirect potable use. 

PMID- 24037166
TI  - Removal of titanium dioxide nanoparticles by coagulation: effects of coagulants,
      typical ions, alkalinity and natural organic matters.
AB  - To investigate the possibility of removing titanium dioxide nanoparticles (TiO2
      NPs) from water by coagulation, as well as to find the optimal coagulant and
      experimental conditions for TiO2 NP removal, four types of coagulant were
      adopted: polyferric sulfate (PFS), ferric chloride (FeCl3), polyaluminum chloride
      (PACl), and alum (Al2(SO4)3). It was found that the removal of TiO2 NPs by
      coagulation was affected by ionic strength, alkalinity, as well as types and
      dosages of coagulants. PFS and FeCl3 achieved much higher removal efficiency of
      TiO2 NPs than PACl and Al2(SO4)3 did. For 30 mg/L TiO2 NPs, a dosage of 0.3 mM
      PFS (as Fe) achieved 84% removal after coagulation followed by 30 min settlement.
      Optimal ionic strength (0.1 M NaCl or 0.03 M CaCl2) is of vital importance for
      the performance of PFS. Na2SO4 is unfavorable for the performance of PFS. Optimal
      alkalinity (0.01-0.03 M NaHCO3) is necessary for FeCl3 to remove TiO2 NPs.
      Natural organic matter, as represented by humic acid (HA) up to 11 mg/L, reduces
      the removal of TiO2 NPs by coagulation. These findings indicate that coagulation
      is a good option for the removal of TiO2 NPs from water, and more attention
      should be paid to the effects of water quality when using coagulation to remove
      TiO2 NPs from aqueous matrices. This provides a possible solution to alleviate
      the potential hazard caused by TiO2 NPs. 

PMID- 24037167
TI  - Tech-IA floating system introduced in urban wastewater treatment plants in the
      Veneto region - Italy.
AB  - The performance of three integrated wetland treatment plants (horizontal sub
      surface flow (h-SSF) and floating treatment wetland (FTW) with differentiated
      primary treatments) designed for treating domestic wastewater was investigated,
      monitoring total (TN), nitrate (NO3-N), nitrite (NO2-N) and ammonia nitrogen (NH4
      N), total (TP) and phosphate phosphorus (PO4-P), chemical (COD) and biological
      oxygen demand (BOD5), and dissolved oxygen (DO) at the inlet and outlet of each
      wetland section from February 2011 to June 2012. Sediments settled in the FTW
      were collected and analyzed. The growth of plants in each system was also
      monitored, observing their general conditions. The chemical-physical
      characteristics of the pretreated domestic wastewater depended on the primary
      treatment installed. During the monitoring period we observed different reduction
      performance of the wetland sector in the three sites. In general, the wetland
      systems demonstrated the capacity to reduce TN, COD, BOD5 and Escherichia coli,
      whereas NO3-N and NH4-N removal was strictly influenced by the chemical
      conditions, in particular DO concentration, in the h-SSF and FTW. Vegetation
      (Phragmites australis, Alnus glutinosa and Salix eleagnos) was well established
      in the h-SSF as well as in the floating elements (Iris pseudacorus), although
      there were some signs of predation. FTW is a relatively novel wetland system, so
      the results obtained from this study can pave the way for the application of this
      technology. 

PMID- 24037168
TI  - Activated carbon fiber felt and polymer fiber as biofilm carrier in a modified
      University of Cape Town process for sewage treatment.
AB  - Biofilms on fiber-based carriers have attracted much concern in wastewater
      treatment processes recently. In this study: (1) a novel sandwich structure fiber
      based biofilm carrier was produced, which consisted of an inner core composed of
      polyacrylonitrile-based activated carbon fiber felt (PAN-ACFF) and an outer coat
      made of polyester reticular cloth with polypropylene fiber loops; (2) the novel
      carrier was filled in a step-feeding pilot-scale modified University of Cape Town
      process (MUCT) for sewage treatment; the MUCT contained a series of pre
      anoxic/anaerobic/anoxic-1/anoxic-2/oxic tanks, wherein nitrification liquor was
      recycled to the anoxic-2 tank and an extra liquor return from the anoxic-1 to the
      pre-anoxic tank was set up; and (3) the removal efficiencies of chemical oxygen
      demand (COD), total nitrogen (TN) and total phosphorus (TP) were continuously
      tested for two periods as operational parameters alternated. The optimum values
      were collected in Period II, when the influent loads were 2,100.6 +/- 120.3
      gCOD/(d m(3)), 205.5 +/- 20.4 gTN/(d m(3)), 39.9 +/- 3.9 gTP/(d m(3)), the
      removal percentages were 93.1 +/- 1.1% of COD, 39.4 +/- 3.5% of TN, and 84.6 +/-
      3.4% of TP. For COD, NH4(+)-N, and TP, the specific removal loads of filler were
      291.5 +/- 18.2, 22.9 +/- 3.1, 4.8 +/- 0.5 (g d)/kg. 

PMID- 24037169
TI  - Modeling trichloroethene reduction in a hydrogen-based biofilm.
AB  - We constructed a multispecies biofilm model for simultaneous reduction of
      trichloroethene (TCE) and nitrate (NO3(-)) in the biofilm of a H2-based membrane
      biofilm reactor (MBfR). The one-dimensional model includes dual-substrate Monod
      kinetics for a steady-state biofilm with multiple solid and dissolved components.
      The model has five solid components: autotrophic denitrifying bacteria (ADB),
      heterotrophic denitrifying bacteria (HDB), Dehalococcoides (DHC), inert biomass
      (IB), and extracellular polymeric substances (EPS). The model has eight dissolved
      components: NO3(-), TCE, dichloroethene (DCE), vinyl chloride (VC), ethene,
      hydrogen (H2), substrate-utilization-associated products (UAP), and biomass
      associated products (BAP). We used this model to simulate a bench-scale
      experiment in a H2-based MBfR. The model simulated the trends well: almost
      complete removal of nitrate, incomplete reduction of TCE, and almost no
      accumulation of DCE and VC. To gain insight into reductive dehalogenation in a H2
      based MBfR, we also simulated the concentrations of nitrate, TCE, DCE, VC, and
      ethene in the reactor effluent while varying the influent nitrate concentration.
      Simultaneous low concentrations of nitrate and the three chlorinated ethenes can
      occur as long as the influent ratio of NO3(-) to TCE is not too large, so that
      DHC are a significant fraction of the biofilm. 

PMID- 24037170
TI  - Removal of persistent organic pollutants from landfill leachates treated in three
      constructed wetland systems.
AB  - The objective of the study was assessment of occurrence and removal of two groups
      of persistent organic pollutants: polycyclic aromatic hydrocarbons (PAHs) and
      polychlorinated biphenyls (PCBs) in landfill leachate (LL) treated in three
      constructed wetland systems (CWs) of different construction and flow regime. Two
      subsurface flow systems (SSF) were analyzed: one with horizontal flow and the
      second one consisting of two vertical flow beds followed by a horizontal flow
      bed. The third CW was a surface flow (SF) system, consisting of 10 ponds
      connected in series. The concentrations of 12 PAHs and 7 PCBs were measured in
      the samples of LL after subsequent treatment stages and in the sediment samples
      from the SF system as well as in the substrate samples from the SSF flow systems.
      It was confirmed that the major mechanism of PCB and PAH removal in CW systems
      was adsorption to the bottom sediments (in the SF system) or substrate of the
      beds (in the SSF systems) as well as adsorption to suspended solids, followed by
      sedimentation. The compounds characterized by higher octanol/water partition
      coefficient were more effectively retained in the sediments. Also removal of
      these substances occurred in the earlier stages of treatment. 

PMID- 24037171
TI  - Electrochemical oxidation of wastewater - opportunities and drawbacks.
AB  - Electrochemical oxidation by means of boron-doped diamond (BDD) anodes generates
      a very efficient oxidizing environment by forming hydroxyl radicals, providing
      effective water purification for elimination of persistent pollutants. In this
      project the degradation rates of organic and inorganic substances are
      investigated. Experiments were performed in laboratory and pilot scale with
      synthetic and industrial wastewaters. Performance parameters were evaluated in
      terms of total organic carbon/chemical oxygen demand (COD) removal, specific
      energy consumption and current efficiency. The integration of this advanced
      oxidation technology combined with conventional technology was then applied in a
      wastewater treatment concept of landfill leachate. The raw leachate with a low
      biochemical oxygen demand/COD ratio was electrochemically oxidized to prepare the
      purified leachate for discharge into a sewage system or a receiving water body.
      The cost estimation regarding operation and capital costs addresses the economics
      for the treatment of heavily polluted effluents. 

PMID- 24037172
TI  - Institutional trajectory for diffusing on-site wastewater treatment in urban
      China.
AB  - Urban water scarcity has been an issue for a long time in China while water
      pollution has attracted more and more attention over the last two decades.
      Recently, on-site wastewater treatment (OST) has been proposed as a meaningful
      alternative to deal with both water pollution and water scarcity in cities in a
      more sustainable way. However, the diffusion of such an OST system is still slow
      and often hindered by mismatched regulation, city planning and policy
      interventions. This paper is intended to explore potential solutions from
      institutional and governance perspectives. Based on expert interviews and in
      depth analysis of an OST system in Kunming, an improved trajectory for diffusing
      OST in urban China is developed, which includes reformed decision-making and
      operational procedures, role transition of relevant stakeholders, and improved
      financing mechanisms. The results might give some suggestions for the transition
      of urban water management in other newly industrializing countries. 

PMID- 24037173
TI  - Evaluation of overland flow model for a hillslope using laboratory flume data.
AB  - Comprehensive modelling of overland flow requires models for both rill and
      interrill area overland flow. Evaluation of a physically based mathematical model
      for simulating overland flow generated on rill and interrill areas of hillslope
      was done using a data set gathered from a laboratory experimental setup. A
      rainfall simulator has been constructed together with a 6.50 m * 1.36 m erosion
      flume that can be given adjustable slopes in both longitudinal and lateral
      directions. The model was calibrated and validated using the experimental results
      from the setup of the flume having 5% lateral and 10% longitudinal slopes where
      rainfall intensities of 105 and 45 mm/hr were induced with the use of nozzles.
      Results show that for the given slope combination, the model was capable of
      simulating the flow coming from the rill and interrill areas for the two
      different rainfall intensities. It was found that significantly more of the flow
      occurred in the form of the rill flow. The model studied here can be used for the
      better prediction of overland flow and can also be used as a building block for
      an associated erosion and sediment transport model. 

PMID- 24037174
TI  - Reconstruction of a constructed wetland with horizontal subsurface flow after 18
      years of operation.
AB  - The constructed wetland (CW) for 326 PE with horizontal subsurface flow at
      Kotencice, Central Bohemia, Czech Republic, was built in 1994. Despite the
      relatively high efficiency of the CW, the filtration beds suffered from clogging,
      and therefore it was decided in 2011 to rebuild the whole system. The new
      treatment system was built as an experimental system consisting of four different
      combinations of horizontal and vertical beds. The major aim of the design was to
      determine the best hybrid combination which then could be used in the future for
      refurbishment of older horizontal flow CWs or for the new systems. The mechanical
      pretreatment consists of mechanical bar screens, a new Imhoff tank, and the
      original settling tank which has been converted into the accumulation tank from
      where the wastewater is pumped into the wetlands. The filters are planted with
      Phragmites australis, Phalaris arundinacea, Iris pseudacorus, Iris sibirica,
      Glyceria maxima and Lythrum salicaria in order to evaluate and compare various
      plant species' effect on the treatment process. The new technology includes a
      tertiary treatment which consists of a greenhouse with a photo-reactor for the
      cultivation of algae and hydroponic systems (residual nutrients removal), sludge
      reed-beds and a composting field. 

PMID- 24037175
TI  - Comparison of 4D-microSPECT and microCT for murine cardiac function.
AB  - PURPOSE: The objective of this study was to compare a new generation of four
      dimensional micro-single photon emission computed tomography (microSPECT) with
      microCT for the quantitative in vivo assessment of murine cardiac function.
      PROCEDURES: Four-dimensional isotropic cardiac images were acquired from
      anesthetized normal C57BL/6 mice with either microSPECT (n = 6) or microCT (n =
      6). One additional mouse with myocardial infarction (MI) was scanned with both
      modalities. Prior to imaging, mice were injected with either technetium
      tetrofosmin for microSPECT or a liposomal blood pool contrast agent for microCT.
      Segmentation of the left ventricle (LV) was performed using Vitrea (Vital Images)
      software, to derive global and regional function. RESULTS: Measures of global LV
      function between microSPECT and microCT groups were comparable (e.g., ejection
      fraction = 71 +/- 6 % microSPECT and 68 +/- 4 % microCT). Regional functional
      indices (wall motion, wall thickening, regional ejection fraction) were also
      similar for the two modalities. In the mouse with MI, microSPECT identified a
      large perfusion defect that was not evident with microCT. CONCLUSIONS: Despite
      lower spatial resolution, microSPECT was comparable to microCT in the
      quantitative evaluation of cardiac function. MicroSPECT offers an advantage over
      microCT in the ability to evaluate simultaneously myocardial radiotracer
      distribution and function, simultaneously. MicroSPECT should be considered as an
      alternative to microCT and magnetic resonance for preclinical cardiac imaging in
      the mouse.

PMID- 24037177
TI  - Early congenital syphilis presenting with vesicobullous eruptions beyond
      palmoplantar regions.

PMID- 24037176
TI  - Shifting focus in optical image-guided cancer therapy.
AB  - Cancer patients could benefit from a surgical procedure that helps the surgeon to
      determine adequate tumor resection margins. Systemic injection of tumor-specific
      fluorescence agents with subsequent intraoperative optical imaging can guide the
      surgeon in this process. However, tumor heterogeneity hampers tumor-specific
      targeting. In addition, determination of adequate resection margins can be very
      challenging due to invasive tumor strands that are difficult to resolve and
      because of the confounding effect of variations in tissue optical properties in
      the surgical margin. We provide an overview of the "classic approach" of imaging
      tumor-specific targets or tumor-associated pathophysiological processes, and
      explain the limitations of these targeting strategies. It is proposed that
      problems of tumor heterogeneity can theoretically be circumvented by shifting
      focus of tumor targeting towards the follicle-stimulating hormone receptor
      (FSHR). Furthermore, we discuss why objective determination of resection margins
      is required to improve resection of the invasive strands, a goal that may be
      achieved by targeting the FSHR. When invasive strands would nevertheless extend
      beyond such a standardized resection margin, we suggest that adjuvant
      photodynamic therapy would be a very suitable therapeutic regimen. Finally, we
      describe how point optical spectroscopy can be used to scrutinize suspect tissue
      that is difficult to differentiate from normal tissue by measuring the local
      tissue optical properties to recover a local intrinsic fluorescence measurement. 

PMID- 24037178
TI  - Use of a combination of the RDC method and NOESY NMR spectroscopy to determine
      the structure of Alzheimer's amyloid Abeta10-35 peptide in solution and in SDS
      micelles.
AB  - The spatial structure of Alzheimer's amyloid Abeta10-35-NH2 peptide in aqueous
      solution at pH 7.3 and in SDS micelles was investigated by use of a combination
      of the residual dipolar coupling method and two-dimensional NMR spectroscopy
      (TOCSY, NOESY). At pH 7.3 Abeta10-35-NH2 adopts a compact random-coil
      conformation whereas in SDS micellar solutions two helical regions (residues 13
      23 and 30-35) of Abeta10-35-NH2 were observed. By use of experimental data, the
      structure of "peptide-micelle" complex was determined; it was found that Abeta10
      35-NH2 peptide binds to the micelle surface at two regions (residues 17-20 and 29
      35).

PMID- 24037179
TI  - Determining the ventilation and aerosol deposition rates from routine indoor-air
      measurements.
AB  - Measurement of air exchange rate provides critical information in energy and
      indoor-air quality studies. Continuous measurement of ventilation rates is a
      rather costly exercise and requires specific instrumentation. In this work, an
      alternative methodology is proposed and tested, where the air exchange rate is
      calculated by utilizing indoor and outdoor routine measurements of a common
      pollutant such as SO2, whereas the uncertainties induced in the calculations are
      analytically determined. The application of this methodology is demonstrated, for
      three residential microenvironments in Athens, Greece, and the results are also
      compared against ventilation rates calculated from differential pressure
      measurements. The calculated time resolved ventilation rates were applied to the
      mass balance equation to estimate the particle loss rate which was found to agree
      with literature values at an average of 0.50 h(-1). The proposed method was
      further evaluated by applying a mass balance numerical model for the calculation
      of the indoor aerosol number concentrations, using the previously calculated
      ventilation rate, the outdoor measured number concentrations and the particle
      loss rates as input values. The model results for the indoors' concentrations
      were found to be compared well with the experimentally measured values. 

PMID- 24037180
TI  - The challenges of conducting environmental research on privately owned land.
AB  - Accessing research sites is an integral part of a research in the world today.
      Researching sites on privately owned lands creates unique challenges when
      compared to conducting research on government or publicly owned land. This study
      explores different methods for obtaining landowner information, permission to
      sample privately owned sites, and assesses the time it takes to obtain permission
      for randomly selected study sites. During the study, researchers contacted 390
      landowners to obtain permission to sample wetlands on privately owned lands. A
      variety of methods were used to contact landowners and determine which methods
      were most effective for obtaining permission. Methods included face-to-face
      discussion, phone calls, and mailed response letters. It took approximately 9
      months to obtain landowner information, contact landowners, and obtain permission
      to sample sites. The most effective method for obtaining permission to sample
      sites was through face-to-face discussions with landowners. Overall, it took a
      longer period of time to obtain permission for the survey than it did to sample
      sites. Information from this study can be used by anyone conducting research on
      private land to better estimate the time it will take to obtain permission to
      sample sites and to estimate the most effective way to obtain permission based on
      project finances and available personnel. 

PMID- 24037181
TI  - CD40 interacts directly with RAG1 and RAG2 in autoaggressive T cells and Fas
      prevents CD40-induced RAG expression.
AB  - CD4(+) T cells expressing CD40 (Th40 cells) constitute a pathogenic T-cell subset
      that is necessary and sufficient to transfer autoimmune disease. We have
      previously demonstrated that CD40 signals peripheral Th40 cells to induce RAG1
      and RAG2 expression, proteins necessary for the expression of T-cell receptor
      (TCR), leading to TCR revision. The dependency of TCR expression in the thymus on
      RAG proteins has long been known. However, despite numerous publications, there
      is controversy as to whether TCR expression can be altered in the periphery, post
      thymic selective pressures. Therefore, a better understanding of TCR expression
      in primary peripheral cells is needed. We now show that the CD40 protein itself
      interacts with RAG1 and RAG2 as well as with Ku70 and translocates to the nucleus
      in Th40 cells. This indicates that the CD40 molecule is closely involved in the
      mechanism of TCR expression in the periphery. In addition, Fas signals act as a
      silencing mechanism for CD40-induced RAGs and prevent CD40 translocation to the
      nucleus. It will be important to further understand the involvement of CD40 in
      peripheral TCR expression and how TCR revision impacts auto-antigen recognition
      in order to effectively target and tolerize autoaggressive T cells in autoimmune
      disease. 

PMID- 24037183
TI  - CD52 as both a marker and an effector molecule of T cells with regulatory action:
      Identification of novel regulatory T cells.

PMID- 24037182
TI  - SOCS3 dictates the transition of divergent time-phased events in granulocyte TNF
      alpha signaling.
AB  - Tumor-necrosis factor-alpha (TNF-alpha)-driven nuclear factor-kappaB (NF-kappaB)
      activation and apoptosis are opposing pathways; the growing recognition of these
      conflicting roles of TNF-alpha is perplexing. Here, we show that inflammation and
      apoptosis are time-phased events following TNF-alpha signaling and that emergence
      of suppressor of cytokine signaling 3 (SOCS3) expression limits the ongoing NF
      kappaB activation and promotes apoptosis; further, we suggest an altered view of
      how inflammatory diseases are initiated and sustained. In vitro, TNF-alpha (50
      ng/ml) induced granulocyte SOCS3 protein, inhibited nuclear accumulation of the
      p65NF-kappaB subunit and enhanced apoptosis, as shown by DNA laddering, annexin V
      positivity, and overexpression of caspase-3 and Bax in the late phase, whereas
      the early phase was marked by NF-kappaB activation. Conversely, SOCS3 knockdown
      by small interfering RNA (siRNA) inhibited granulocyte apoptosis and enhanced
      nuclear accumulation of p65 and 5' lipooxygenase expression in the late phase of
      TNF-alpha signaling. As apoptosis is associated with SOCS3 abundance, we suggest
      that these divergent TNF-alpha-driven events are time-phased, interconnected,
      opposing control mechanisms and one of the central features through which the
      immune system resolves pulmonary inflammation. Dysregulation may initiate mucosal
      inflammation, thus changing the landscape of asthma therapy. 

PMID- 24037184
TI  - The interaction between the helicase DHX33 and IPS-1 as a novel pathway to sense
      double-stranded RNA and RNA viruses in myeloid dendritic cells.
AB  - In eukaryotes, there are at least 60 members of the DExD/H helicase family, many
      of which are able to sense viral nucleic acids. By screening all known family
      members, we identified the helicase DHX33 as a novel double-stranded RNA (dsRNA)
      sensor in myeloid dendritic cells (mDCs). The knockdown of DHX33 using small
      heteroduplex RNA (shRNA) blocked the ability of mDCs to produce type I interferon
      (IFN) in response to poly I:C and reovirus. The HELICc domain of DHX33 was shown
      to bind poly I:C. The interaction between DHX33 and IPS-1 is mediated by the
      HELICc region of DHX33 and the C-terminal domain of IPS-1 (also referred to MAVS
      and VISA). The inhibition of DHX33 expression by RNA interference blocked the
      poly I:C-induced activation of MAP kinases, NF-kappaB and IRF3. The interaction
      between the helicase DHX33 and IPS-1 was independent of RIG-I/MDA5 and may be a
      novel pathway for sensing poly I:C and RNA viruses in mDCs. 

PMID- 24037185
TI  - Signaling at the immune synapse: vesicular trafficking takes the stage.

PMID- 24037186
TI  - Symbiotic association between symbiodinium and the gastropod Strombus gigas:
      larval acquisition of symbionts.
AB  - The importance of the dinoflagellate Symbiodinium sp. was studied in the early
      life stages of the gastropod Strombus gigas. This dinoflagellate was not found in
      the eggs or the gelatinous mass surrounding the eggs of the mollusk; therefore,
      Symbiodinium is not inherited directly. To determine whether the planktonic
      veligers can acquire these algae from the environment, they were exposed to
      freshly isolated Symbiodinium from adult S. gigas (homologous). The optimal stage
      for Symbiodinium inoculation was found at 48 h post-hatching. Survival and growth
      rates of veligers and juveniles were higher when inoculated with freshly isolated
      Symbiodinium in conjunction with daily feeding of Isochrysis spp. Veligers
      inoculated with Symbiodinium freshly isolated from three host species elicited
      distinct responses: (1) veligers did not take up Symbiodinium isolated from the
      hydrozoan Millepora alcicornis suggesting that there is discrimination on contact
      prior to ingestion, (2) veligers did take up Symbiodinium isolated from the
      anemone Bartholomea annulata, but the algae did not persist in the host tissue
      suggesting that selection against this type took place after ingestion or that
      the algae did not divide in the host, and (3) veligers did take up Symbiodinium
      isolated from Pterogorgia anceps where it persisted and was associated with
      metamorphosis of the larvae. In contrast, the Symbiodinium freshly isolated from
      S. gigas were not associated with metamorphosis and required an inducer such as
      the red alga Laurencia poitei. These data present a significant advancement for
      the establishment of a new approach in the aquaculture of this important but
      declining Caribbean species. 

PMID- 24037187
TI  - Kazal-type serine proteinase inhibitors in the midgut of Phlebotomus papatasi.
AB  - Sandflies (Diptera: Psychodidae) are important disease vectors of parasites of
      the genus Leishmania, as well as bacteria and viruses. Following studies of the
      midgut transcriptome of Phlebotomus papatasi, the principal vector of Leishmania
      major, two non-classical Kazal-type serine proteinase inhibitors were identified
      (PpKzl1 and PpKzl2). Analyses of expression profiles indicated that PpKzl1 and
      PpKzl2 transcripts are both regulated by blood-feeding in the midgut of P.
      papatasi and are also expressed in males, larva and pupa. We expressed a
      recombinant PpKzl2 in a mammalian expression system (CHO-S free style cells) that
      was applied to in vitro studies to assess serine proteinase inhibition.
      Recombinant PpKzl2 inhibited alpha-chymotrypsin to 9.4% residual activity and
      also inhibited alpha-thrombin and trypsin to 33.5% and 63.9% residual activity,
      suggesting that native PpKzl2 is an active serine proteinase inhibitor and likely
      involved in regulating digestive enzymes in the midgut. Early stages of
      Leishmania are susceptible to killing by digestive proteinases in the sandfly
      midgut. Thus, characterising serine proteinase inhibitors may provide new targets
      and strategies to prevent transmission of Leishmania. 

PMID- 24037188
TI  - Leishmania amazonensis exhibits phosphatidylserine-dependent procoagulant
      activity, a process that is counteracted by sandfly saliva.
AB  - Leishmania parasites expose phosphatidylserine (PS) on their surface, a process
      that has been associated with regulation of host's immune responses. In this
      study we demonstrate that PS exposure by metacyclic promastigotes of Leishmania
      amazonensis favours blood coagulation. L. amazonensis accelerates in vitro
      coagulation of human plasma. In addition, L. amazonensis supports the assembly of
      the prothrombinase complex, thus promoting thrombin formation. This process was
      reversed by annexin V which blocks PS binding sites. During blood meal, Lutzomyia
      longipalpis sandfly inject saliva in the bite site, which has a series of
      pharmacologically active compounds that inhibit blood coagulation. Since saliva
      and parasites are co-injected in the host during natural transmission, we
      evaluated the anticoagulant properties of sandfly saliva in counteracting the
      procoagulant activity of L. amazonensis . Lu. longipalpis saliva reverses plasma
      clotting promoted by promastigotes. It also inhibits thrombin formation by the
      prothrombinase complex assembled either in phosphatidylcholine (PC)/PS vesicles
      or in L. amazonensis . Sandfly saliva inhibits factor X activation by the
      intrinsic tenase complex assembled on PC/PS vesicles and blocks factor Xa
      catalytic activity. Altogether our results show that metacyclic promastigotes of
      L. amazonensis are procoagulant due to PS exposure. Notably, this effect is
      efficiently counteracted by sandfly saliva. 

PMID- 24037189
TI  - Apoptosis of non-parasitised red blood cells in Plasmodium yoelii malaria.
AB  - Recently, while studying erythrocytic apoptosis during Plasmodium yoelii
      infection, we observed an increase in the levels of non-parasitised red blood
      cell (nRBC) apoptosis, which could be related to malarial anaemia. Therefore, in
      the present study, we attempted to investigate whether nRBC apoptosis is
      associated with the peripheral RBC count, parasite load or immune response. To
      this end, BALB/c mice were infected with P. yoelii 17XL and nRBC apoptosis,
      number of peripheral RBCs, parasitaemia and plasmatic levels of cytokines, nitric
      oxide and anti-RBC antibodies were evaluated at the early and late stages of
      anaemia. The apoptosis of nRBCs increased at the late stage and was associated
      with parasitaemia, but not with the intensity of the immune response. The
      increased percentage of nRBC apoptosis that was observed when anaemia was
      accentuated was not related to a reduction in peripheral RBCs. We conclude that
      nRBC apoptosis in P. yoelii malaria appears to be induced in response to a high
      parasite load. Further studies on malaria models in which acute anaemia develops
      during low parasitaemia are needed to identify the potential pathogenic role of
      nRBC apoptosis. 

PMID- 24037190
TI  - Effect of treatment with cyclophosphamide in low doses upon the onset of delayed
      type hypersensitivity in mice chronically infected with Trypanosoma cruzi:
      involvement of heart interstitial dendritic cells.
AB  - Acute infection with Trypanosoma cruzi results in intense myocarditis, which
      progresses to a chronic, asymptomatic indeterminate form. The evolution toward
      this chronic cardiac form occurs in approximately 30% of all cases of T. cruzi
      infection. Suppression of delayed type hypersensitivity (DTH) has been proposed
      as a potential explanation of the indeterminate form. We investigated the effect
      of cyclophosphamide (CYCL) treatment on the regulatory mechanism of DTH and the
      participation of heart interstitial dendritic cells (IDCs) in this process using
      BALB/c mice chronically infected with T. cruzi. One group was treated with CYCL
      (20 mg/kg body weight) for one month. A DTH skin test was performed by
      intradermal injection of T. cruzi antigen (3 mg/mL) in the hind-footpad and
      measured the skin thickness after 24 h, 48 h and 72 h. The skin test revealed
      increased thickness in antigen-injected footpads, which was more evident in the
      mice treated with CYCL than in those mice that did not receive treatment. The
      thickened regions were characterised by perivascular infiltrates and areas of
      necrosis. Intense lesions of the myocardium were present in three/16 cases and
      included large areas of necrosis. Morphometric evaluation of lymphocytes showed a
      predominance of TCD8 cells. Heart IDCs were immunolabelled with specific
      antibodies (CD11b and CD11c) and T. cruzi antigens were detected using a specific
      anti-T. cruzi antibody. Identification of T. cruzi antigens, sequestered in these
      cells using specific anti-T. cruzi antibodies was done, showing a significant
      increase in the number of these cells in treated mice. These results indicate
      that IDCs participate in the regulatory mechanisms of DTH response to T. cruzi
      infection. 

PMID- 24037191
TI  - Identification and characterisation of microRNAs in young adults of
      Angiostrongylus cantonensis via a deep-sequencing approach.
AB  - Angiostrongylus cantonensis is an important causative agent of eosinophilic
      meningitis and eosinophilic meningoencephalitis in humans. MicroRNAs (miRNAs) are
      small non-coding RNAs that participate in a wide range of biological processes.
      This study employed a deep-sequencing approach to study miRNAs from young adults
      of A. cantonensis. Based on 16,880,456 high-quality reads, 252 conserved mature
      miRNAs including 10 antisense miRNAs that belonging to 90 families, together with
      10 antisense miRNAs were identified and characterised. Among these sequences, 53
      miRNAs from 25 families displayed 50 or more reads. The conserved miRNA families
      were divided into four groups according to their phylogenetic distribution and a
      total of nine families without any members showing homology to other nematodes or
      adult worms were identified. Stem-loop real-time polymerase chain reaction
      analysis of aca-miR-1-1 and aca-miR-71-1 demonstrated that their level of
      expression increased dramatically from infective larvae to young adults and then
      decreased in adult worms, with the male worms exhibiting significantly higher
      levels of expression than female worms. These findings provide information
      related to the regulation of gene expression during the growth, development and
      pathogenesis of young adults of A. cantonensis. 

PMID- 24037192
TI  - A directed approach for the identification of transcripts harbouring the spliced
      leader sequence and the effect of trans-splicing knockdown in Schistosoma
      mansoni.
AB  - Schistosomiasis is a major neglected tropical disease caused by trematodes from
      the genus Schistosoma. Because schistosomes exhibit a complex life cycle and
      numerous mechanisms for regulating gene expression, it is believed that spliced
      leader (SL) trans-splicing could play an important role in the biology of these
      parasites. The purpose of this study was to investigate the function of trans
      splicing in Schistosoma mansoni through analysis of genes that may be regulated
      by this mechanism and via silencing SL-containing transcripts through RNA
      interference. Here, we report our analysis of SL transcript-enriched cDNA
      libraries from different S. mansoni life stages. Our results show that the trans
      splicing mechanism is apparently not associated with specific genes, subcellular
      localisations or life stages. In cross-species comparisons, even though the sets
      of genes that are subject to SL trans-splicing regulation appear to differ
      between organisms, several commonly shared orthologues were observed. Knockdown
      of trans-spliced transcripts in sporocysts resulted in a systemic reduction of
      the expression levels of all tested trans-spliced transcripts; however, the only
      phenotypic effect observed was diminished larval size. Further studies involving
      the findings from this work will provide new insights into the role of trans
      splicing in the biology of S. mansoni and other organisms. All Expressed Sequence
      Tags generated in this study were submitted to dbEST as five different libraries.
      The accessions for each library and for the individual sequences are as follows:
      (i) adult worms of mixed sexes (LIBEST_027999: JZ139310 - JZ139779), (ii) female
      adult worms (LIBEST_028000: JZ139780 - JZ140379), (iii) male adult worms
      (LIBEST_028001: JZ140380 - JZ141002), (iv) eggs (LIBEST_028002: JZ141003 -
      JZ141497) and (v) schistosomula (LIBEST_028003: JZ141498 - JZ141974). 

PMID- 24037193
TI  - Characterisation of pks15/1 in clinical isolates of Mycobacterium tuberculosis
      from Mexico.
AB  - Tuberculosis (TB) is an infectocontagious respiratory disease caused by members
      of the Mycobacterium tuberculosis complex. A 7 base pair (bp) deletion in the
      locus polyketide synthase (pks)15/1 is described as polymorphic among members of
      the M. tuberculosis complex, enabling the identification of Euro-American, Indo
      Oceanic and Asian lineages. The aim of this study was to characterise this locus
      in TB isolates from Mexico. One hundred twenty clinical isolates were recovered
      from the states of Veracruz and Estado de Mexico. We determined the nucleotide
      sequence of a +/- 400 bp fragment of the locus pks15/1, while genotypic
      characterisation was performed by spoligotyping. One hundred and fifty isolates
      contained the 7 bp deletion, while five had the wild type locus. Lineages X
      (22%), LAM (18%) and T (17%) were the most frequent; only three (2%) of the
      isolates were identified as Beijing and two (1%) EAI-Manila. The wild type
      pks15/1 locus was observed in all Asian lineage isolates tested. Our results
      confirm the utility of locus pks15/1 as a molecular marker for identifying Asian
      lineages of the M. tuberculosis complex. This marker could be of great value in
      the epidemiological surveillance of TB, especially in countries like Mexico,
      where the prevalence of such lineages is unknown. 

PMID- 24037194
TI  - Antagonistic activity expressed by Shigella sonnei: identification of a putative
      new bacteriocin.
AB  - Bacteriocins are antibacterial, proteinaceous substances that mediate microbial
      dynamics. Bacteriocin production is a highly disseminated property among all
      major lineages of bacteria, including Shigella. In this paper, we addressed the
      purification and characterisation of a bacteriocin produced by a Shigella sonnei
      strain (SS9) isolated from a child with acute diarrhoea. The substance was
      purified through ammonium-sulphate precipitation and sequential steps of
      chromatography. The intracellular fraction obtained at 75% ammonium sulphate
      maintained activity following exposure to pH values from 1-11 and storage at 
      80oC for more than two years and was inactivated by high temperatures and
      proteases. The molecular mass of the purified bacteriocin was determined by mass
      spectrometry to be 18.56 kDa. The N-terminal sequence of the bacteriocin did not
      match any other antibacterial proteins described. A putative new bacteriocin
      produced by S. sonnei has been detected. This bacteriocin may represent a newly
      described protein or a previously described protein with a newly detected
      function. Considering that SS9 expresses antagonism against other diarrhoeagenic
      bacteria, the bacteriocin may contribute to S. sonnei virulence and is
      potentially applicable to either preventing or controlling diarrhoeal disease. 

PMID- 24037195
TI  - Standardisation of Western blotting to detect HTLV-1 antibodies synthesised in
      the central nervous system of HAM/TSP patients.
AB  - Intrathecal synthesis of human T-lymphotropic virus type 1 (HTLV-1) antibodies
      (Abs) represents conclusive evidence of a specific immune response in the central
      nervous system of HTLV-1 associated myelopathy/tropical spastic paraparesis
      (HAM/TSP) patients. Western blotting (WB) for HTLV Abs in serum is a confirmatory
      test for HTLV-1 infection. The aim of this study was to standardise the Western
      blot to demonstrate the intrathecal pattern of Abs against HTLV-1 proteins in
      HAM/TSP patients. Paired cerebrospinal fluid (CSF) and serum samples were
      selected from 20 patients with definite HAM/TSP, 19 HTLV-1 seronegative patients
      and two HTLV-1 patients without definite HAM/TSP. The presence of reactive bands
      of greater intensity in the CSF compared to serum (or bands in only the CSF)
      indicated the intrathecal synthesis of anti-HTLV-1 Abs. All definite HAM/TSP
      patients presented with an intrathecal synthesis of anti-HTLV-1 Abs; these Abs
      were not detected in the control patients. The most frequent intrathecal targets
      of anti-HTLV-1 Abs were GD21, rgp46-I and p24 and, to a lesser extent, p19, p26,
      p28, p32, p36, p53 gp21 and gp46. The intrathecal immune response against env
      (GD21 and rgp46-I) and gag (p24) proteins represents the most important humoral
      pattern in HAM/TSP. This response may be used as a diagnostic marker, considering
      the frequent association of intrathecal anti-HTLV-1 Ab synthesis with HAM/TSP and
      the pathogenesis of this neurological disease. 

PMID- 24037196
TI  - Detection of the B"-GWGR variant in the southernmost region of Brazil: unveiling
      the complexity of the human immunodeficiency virus-1 subtype B epidemic.
AB  - Typical human immunodeficiency virus-1 subtype B (HIV-1B) sequences present a
      GPGR signature at the tip of the variable region 3 (V3) loop; however, unusual
      motifs harbouring a GWGR signature have also been isolated. Although
      epidemiological studies have detected this variant in approximately 17-50% of the
      total infections in Brazil, the prevalence of B"-GWGR in the southernmost region
      of Brazil is not yet clear. This study aimed to investigate the C2-V3 molecular
      diversity of the HIV-1B epidemic in southernmost Brazil. HIV-1 seropositive
      patients were ana-lysed at two distinct time points in the state of Rio Grande do
      Sul (RS98 and RS08) and at one time point in the state of Santa Catarina (SC08).
      Phylogenetic analysis classified 46 individuals in the RS98 group as HIV-1B and
      their molecular signatures were as follows: 26% B"-GWGR, 54% B-GPGR and 20% other
      motifs. In the RS08 group, HIV-1B was present in 32 samples: 22% B"-GWGR, 59% B
      GPGR and 19% other motifs. In the SC08 group, 32 HIV-1B samples were found: 28%
      B"-GWGR, 59% B-GPGR and 13% other motifs. No association could be established
      between the HIV-1B V3 signatures and exposure categories in the HIV-1B epidemic
      in RS. However, B-GPGR seemed to be related to heterosexual individuals in the
      SC08 group. Our results suggest that the established B"-GWGR epidemics in both
      cities have similar patterns, which is likely due to their geographical proximity
      and cultural relationship. 

PMID- 24037199
TI  - Development of the BG-Malaria trap as an alternative to human-landing catches for
      the capture of Anopheles darlingi.
AB  - Although the human-landing catch (HLC) method is the most effective for
      collecting anthropophilic anophelines, it has been increasingly abandoned,
      primarily for ethical considerations. The objective of the present study was to
      develop a new trap for the collection of Anopheles darlingi . The initial trials
      were conducted using the BG-Sentinel trap as a standard for further trap
      development based on colour, airflow direction and illumination. The performance
      of the trap was then compared with those of the CDC, Fay-Prince, counterflow
      geometry trap (CFG) and HLC. All trials were conducted outdoors between 06:00 pm
      08:00 pm. Female specimens of An. darlingi were dissected to determine their
      parity. A total of 8,334 anophelines were captured, of which 4,945 were
      identified as An. darlingi . The best trap configuration was an all-white
      version, with an upward airflow and no required light source. This configuration
      was subsequently named BG-Malaria (BGM). The BGM captured significantly more
      anophelines than any of the other traps tested and was similar to HLC with
      respect to the number and parity of anophelines. The BGM trap can be used as an
      alternative to HLC for collecting anophelines. 

PMID- 24037197
TI  - Inhibition of rotavirus ECwt infection in ICR suckling mice by N-acetylcysteine,
      peroxisome proliferator-activated receptor gamma agonists and cyclooxygenase-2
      inhibitors.
AB  - Live attenuated vaccines have recently been introduced for preventing rotavirus
      disease in children. However, alternative strategies for prevention and treatment
      of rotavirus infection are needed mainly in developing countries where low
      vaccine coverage occurs. In the present work, N-acetylcysteine (NAC), ascorbic
      acid (AA), some nonsteroidal anti-inflammatory drugs (NSAIDs) and peroxisome
      proliferator-activated receptor gamma (PPARgamma) agonists were tested for their
      ability to interfere with rotavirus ECwt infectivity as detected by the
      percentage of viral antigen-positive cells of small intestinal villi isolated
      from ECwt-infected ICR mice. Administration of 6 mg NAC/kg every 8 h for three
      days following the first diarrhoeal episode reduced viral infectivity by about
      90%. Administration of AA, ibuprofen, diclofenac, pioglitazone or rosiglitazone
      decreased viral infectivity by about 55%, 90%, 35%, 32% and 25%, respectively.
      ECwt infection of mice increased expression of cyclooxygenase-2, ERp57, Hsc70, NF
      kappaB, Hsp70, protein disulphide isomerase (PDI) and PPARgamma in intestinal
      villus cells. NAC treatment of ECwt-infected mice reduced Hsc70 and PDI
      expression to levels similar to those observed in villi from uninfected control
      mice. The present results suggest that the drugs tested in the present work could
      be assayed in preventing or treating rotaviral diarrhoea in children and young
      animals. 

PMID- 24037200
TI  - Characterisation of Culex quinquefasciatus (Diptera: Culicidae) larval habitats
      at ground level and temporal fluctuations of larval abundance in Cordoba,
      Argentina.
AB  - The aims of this study were to characterise the ground-level larval habitats of
      the mosquito Culex quinquefasciatus, to determine the relationships between
      habitat characteristics and larval abundance and to examine seasonal larval-stage
      variations in Cordoba city. Every two weeks for two years, 15 larval habitats
      (natural and artificial water bodies, including shallow wells, drains, retention
      ponds, canals and ditches) were visited and sampled for larval mosquitoes. Data
      regarding the water depth, temperature and pH, permanence, the presence of
      aquatic vegetation and the density of collected mosquito larvae were recorded.
      Data on the average air temperatures and accumulated precipitation during the 15
      days prior to each sampling date were also obtained. Cx. quinquefasciatus larvae
      were collected throughout the study period and were generally most abundant in
      the summer season. Generalised linear mixed models indicated the average air
      temperature and presence of dicotyledonous aquatic vegetation as variables that
      served as important predictors of larval densities. Additionally, permanent
      breeding sites supported high larval densities. In Cordoba city and possibly in
      other highly populated cities at the same latitude with the same environmental
      conditions, control programs should focus on permanent larval habitats with
      aquatic vegetation during the early spring, when the Cx. quinquefasciatus
      population begins to increase. 

PMID- 24037198
TI  - Potential biomarkers for the clinical prognosis of severe dengue.
AB  - Currently, several assays can confirm acute dengue infection at the point-of
      care. However, none of these assays can predict the severity of the disease
      symptoms. A prognosis test that predicts the likelihood of a dengue patient to
      develop a severe form of the disease could permit more efficient patient triage
      and treatment. We hypothesise that mRNA expression of apoptosis and innate immune
      response-related genes will be differentially regulated during the early stages
      of dengue and might predict the clinical outcome. Aiming to identify biomarkers
      for dengue prognosis, we extracted mRNA from the peripheral blood mononuclear
      cells of mild and severe dengue patients during the febrile stage of the disease
      to measure the expression levels of selected genes by quantitative polymerase
      chain reaction. The selected candidate biomarkers were previously identified by
      our group as differentially expressed in microarray studies. We verified that the
      mRNA coding for CFD, MAGED1, PSMB9, PRDX4 and FCGR3B were differentially
      expressed between patients who developed clinical symptoms associated with the
      mild type of dengue and patients who showed clinical symptoms associated with
      severe dengue. We suggest that this gene expression panel could putatively serve
      as biomarkers for the clinical prognosis of dengue haemorrhagic fever. 

PMID- 24037201
TI  - The cuticular hydrocarbons of the Triatoma sordida species subcomplex (Hemiptera:
      Reduviidae).
AB  - The cuticular hydrocarbons of the Triatoma sordida subcomplex (Hemiptera:
      Reduviidae: Triatominae) were ana-lysed by gas chromatography and their
      structures identified by mass spectrometry. They comprised mostly n-alkanes and
      methyl-branched alkanes with one-four methyl substitutions. n-alkanes consisted
      of a homologous series from C21-C33 and represented 33-45% of the hydrocarbon
      fraction; n-C29 was the major component. Methyl-branched alkanes showed alkyl
      chains from C24-C43. High molecular weight dimethyl and trimethylalkanes (from
      C35-C39) represented most of the methyl-branched fraction. A few
      tetramethylalkanes were also detected, comprising mostly even-numbered chains.
      Several components such as odd-numbered 3-methylalkanes, dimethylalkanes and
      trimethylalkanes of C37 and C39 showed patterns of variation that allowed the
      differentiation of the species and populations studied. Triatoma guasayana and
      Triatoma patagonica showed the most distinct hydrocarbon patterns within the
      subcomplex. The T. sordida populations from Brazil and Argentina showed
      significantly different hydrocarbon profiles that posed concerns regarding the
      homogeneity of the species. Triatoma garciabesi had a more complex hydrocarbon
      pattern, but it shared some similarity with T. sordida. The quantitative and
      qualitative variations in the cuticular hydrocarbons may help to elucidate the
      relationships between species and populations of this insect group. 

PMID- 24037202
TI  - Revalidation and redescription of Triatoma brasiliensis macromelasoma Galvao,
      1956 and an identification key for the Triatoma brasiliensis complex (Hemiptera:
      Reduviidae: Triatominae).
AB  - Triatoma brasiliensis macromelasoma is revalidated based on the results of
      previous multidisciplinary studies on the Triatoma brasiliensis complex,
      consisting of crossing experiments and morphological, biological, ecological and
      molecular analyses. These taxonomic tools showed the closest relationship between
      T. b. macromelasoma and Triatoma brasiliensis brasiliensis. T. b. macromelasoma
      is redescribed based on specimens collected in the type locality and specimens
      from a F1 colony. The complex now comprises T. b. brasiliensis, T. b.
      macromelasoma, Triatoma melanica, Triatoma juazeirensis and Triatoma sherlocki.
      An identification key for all members of the complex is presented. This detailed
      comparative study of the morphological features of T. b. macromelasoma and the
      remaining members of the complex corroborates results from multidisciplinary
      analyses, suggesting that the subspecific status is applicable. This subspecies
      can be distinguished by the following combination of features: a pronotum with
      1+1 narrow brownish-yellow stripes on the submedian carinae, not attaining its
      apex, hemelytra with membrane cells darkened on the central portion and legs with
      an incomplete brownish-yellow ring on the apical half of the femora. Because the
      T. brasiliensis complex is of distinct epidemiological importance throughout its
      geographic distribution, a precise identification of its five members is
      important for monitoring and controlling actions against Chagas disease
      transmission. 

PMID- 24037203
TI  - Toxicological and biochemical analysis of the susceptibility of sylvatic Triatoma
      infestans from the Andean Valley of Bolivia to organophosphate insecticide.
AB  - To increase our knowledge of the natural susceptibility of Triatoma infestans to
      an organophosphate insecticide, we performed toxicological and biochemical
      studies on three sylvatic populations from Bolivia and two populations from
      domestic dwellings from Bolivia and Argentina. Fifty-per-cent lethal doses (LD50)
      were determined based on the topical application of fenitrothion on first instar
      nymphs and mortality was assessed at 24 h. Both type of populations exhibited
      LD50ratios significantly higher than 1 with a range of the values (1.42-2.47);
      the maximum value were found in a sylvatic (-S) population, Veinte de Octubre-S.
      Samples were biochemically analysed using a glutathione S-transferase activity
      assay. The highest significant activity was obtained for Veinte de Octubre-S and
      the lowest activity was obtained for the reference population (102.69 and 54.23
      pmol per minute per mg of protein respectively). Two out of the three sylvatic
      populations (Veinte de Octubre-S and Kirus Mayu-S) exhibited significantly higher
      glutathione S-transferase activity than that of the reference population. Based
      on this analysis of the natural susceptibility of this organism to
      organophosphate insecticides, continental and focal surveys of organophosphate
      susceptibility should be conducted to evaluate the evolution and distribution of
      this phenomenon. 

PMID- 24037204
TI  - Asymptomatic infection in individuals from the municipality of Barcelos
      (Brazilian Amazon) is not associated with the anti-Plasmodium falciparum
      glycosylphosphatidylinositol antibody response.
AB  - Anti-glycosylphosphatidylinositol (GPI) antibodies (Abs) may reflect and mediate,
      at least partially, anti-disease immunity in malaria by neutralising the toxic
      effect of parasitic GPI. Thus, we assessed the anti-GPI Ab response in
      asymptomatic individuals living in an area of the Brazilian Amazon that has a
      high level of malaria transmission. For comparative purposes, we also
      investigated the Ab response to a crude extract prepared from Plasmodium
      falciparum, the merozoite surface protein (MSP)3 antigen of P. falciparum and the
      MSP 1 antigen of Plasmodium vivax (PvMSP1-19) in these individuals and in Angolan
      patients with acute malaria. Our data suggest that the Ab response against P.
      falciparum GPI is not associated with P. falciparum asymptomatic infection in
      individuals who have been chronically exposed to malaria in the Brazilian Amazon.
      However, this Ab response could be related to ongoing parasitaemia (as was
      previously shown) in the Angolan patients. In addition, our data show that PvMSP1
      19may be a good marker antigen to reflect previous exposure to Plasmodium in
      areas that have a high transmission rate of P. vivax. 

PMID- 24037205
TI  - Red blood cells derived from peripheral blood and bone marrow CD34+ human
      haematopoietic stem cells are permissive to Plasmodium parasites infection.
AB  - The production of fully functional human red cells in vitro from haematopoietic
      stem cells (hHSCs) has been successfully achieved. Recently, the use of hHSCs
      from cord blood represented a major improvement to develop the continuous culture
      system for Plasmodium vivax. Here, we demonstrated that CD34+ hHSCs from
      peripheral blood and bone marrow can be expanded and differentiated to
      reticulocytes using a novel stromal cell. Moreover, these reticulocytes and
      mature red blood cells express surface markers for entrance of malaria parasites
      contain adult haemoglobin and are also permissive to invasion by P. vivax and
      Plasmodium falciparum parasites.

PMID- 24037206
TI  - Optimisation of an asymmetric polymerase chain reaction assay for the
      amplification of single-stranded DNA from Wuchereria bancrofti for
      electrochemical detection.
AB  - Single-stranded DNA (ssDNA) is a prerequisite for electrochemical sensor-based
      detection of parasite DNA and other diagnostic applications. To achieve this
      detection, an asymmetric polymerase chain reaction method was optimised. This
      method facilitates amplification of ssDNA from the human lymphatic filarial
      parasite Wuchereria bancrofti. This procedure produced ssDNA fragments of 188 bp
      in a single step when primer pairs (forward and reverse) were used at a 100:1
      molar ratio in the presence of double-stranded template DNA. The ssDNA thus
      produced was suitable for immobilisation as probe onto the surface of an Indium
      tin oxide electrode and hybridisation in a system for sequence-specific
      electrochemical detection of W. bancrofti. The hybridisation of the ssDNA probe
      and target ssDNA led to considerable decreases in both the anodic and the
      cathodic currents of the system's redox couple compared with the unhybridised DNA
      and could be detected via cyclic voltammetry. This method is reproducible and
      avoids many of the difficulties encountered by conventional methods of filarial
      parasite DNA detection; thus, it has potential in xenomonitoring. 

PMID- 24037207
TI  - Phospholipase gene expression during Paracoccidioides brasiliensis morphological
      transition and infection.
AB  - Phospholipase is an important virulence factor for pathogenic fungi. In this
      study, we demonstrate the following: (i) the Paracoccidioides brasiliensis pld
      gene is preferentially expressed in mycelium cells, (ii) the plb1 gene is mostly
      up-regulated by infection after 6 h of co-infection of MH-S cells or during
      BALB/c mice lung infection, (iii) during lung infection, plb1, plc and pld gene
      expression are significantly increased 6-48 h post-infection compared to 56 days
      after infection, strongly suggesting that phospholipases play a role in the early
      events of infection, but not during the chronic stages of pulmonary infection by
      P. brasiliensis. 

PMID- 24037208
TI  - The antimicrobial susceptibility, biofilm formation and genotypic profiles of
      Staphylococcus haemolyticus from bloodstream infections.
AB  - We analysed the antimicrobial susceptibility, biofilm formation and genotypic
      profiles of 27 isolates of Staphylococcus haemolyticus obtained from the blood of
      19 patients admitted to a hospital in Rio de Janeiro, Brazil. Our analysis
      revealed a clinical significance of 36.8% and a multi-resistance rate of 92.6%
      among these isolates. All but one isolate carried the mecA gene. The
      staphylococcal cassette chromosome mec type I was the most prevalent mec element
      detected (67%). Nevertheless, the isolates showed clonal diversity based on
      pulsed-field gel electrophoresis analysis. The ability to form biofilms was
      detected in 66% of the isolates studied. Surprisingly, no icaAD genes were found
      among the biofilm-producing isolates. 

PMID- 24037209
TI  - Understanding the evaporation of ionic liquids using the example of 1-ethyl-3
      methylimidazolium ethylsulfate.
AB  - In this work we present a comprehensive temperature-dependence analysis of both
      the structural and the dynamic properties of a vaporized ionic liquid (1-ethyl-3
      methylimidazolium ethylsulfate). This particular ionic liquid is known to be
      distillable from experimental studies and thus enables us to deepen the
      understanding of the evaporation mechanism of ionic liquids. We have used ab
      initio molecular dynamics of one ion pair at three different temperatures to
      accurately describe the interactions present in this model ionic liquid. By means
      of radial and spatial distribution functions a large impact on the coordination
      pattern at 400 K is shown which could explain the transfer of one ion pair from
      the bulk to the gas phase. Comparison of the free energy surfaces at 300 K and
      600 K supports the idea of bulk phase-like and gas phase-like ion pairs. The
      different coordination patterns caused by the temperature, describing a loosening
      of the anion side chains, are also well reflected in the power spectra. The
      lifetime analysis of typical conformations for ionic liquids shows a
      characteristic behavior at 400 K (temperature close to the experimental
      evaporation temperature), indicating that conformational changes occur when the
      ionic liquid is evaporated. 

PMID- 24037210
TI  - Association of self-reported race with AIDS death in continuous HAART users in a
      cohort of HIV-infected women in the United States.
AB  - OBJECTIVE: To assess the association of race with clinical outcomes in HIV
      positive women on continuous HAART. DESIGN: Prospective study that enrolled women
      from 1994 to 1995 and 2001 to 2002. SETTING: Women's Interagency HIV Study, a
      community-based cohort in five US cities. PARTICIPANTS: One thousand, four
      hundred and seventy-one HIV-positive continuous HAART users. MAIN OUTCOME
      MEASURES: Times to AIDS and non-AIDS death and incident AIDS-defining illness
      (ADI) after HAART initiation. RESULTS: In adjusted analyses, black vs. white
      women had higher rates of AIDS death [adjusted hazard ratio (aHR) 2.14, 95%
      confidence interval (CI) 1.30, 3.50; P = 0.003] and incident ADI (aHR 1.58, 95%
      CI 1.08, 2.32; P = 0.02), but not non-AIDS death (aHR 0.91, 95% CI 0.59, 1.39; P
      = 0.65). Cumulative AIDS death incidence at 10 years was 17.3 and 8.3% for black
      and white women, respectively. Other significant independent pre-HAART predictors
      of AIDS death included peak viral load (aHR 1.70 per log10, 95% CI 1.34, 2.16; P
      < 0.001), nadir CD4+ cell count (aHR 0.65 per 100 cells/MUl, 95% CI 0.56, 0.76; P
      < 0.001), depressive symptoms by Center for Epidemiology Studies Depression score
      at least 16 (aHR 2.10, 95% CI 1.51, 2.92; P < 0.001), hepatitis C virus infection
      (aHR 1.57, 95% CI 1.02, 2.40; P = 0.04), and HIV acquisition via transfusion (aHR
      2.33, 95% CI 1.21, 4.49; P = 0.01). In models with time-updated HAART adherence,
      association of race with AIDS death remained statistically significant (aHR 3.09,
      95% CI 1.38, 6.93; P = 0.006). CONCLUSION: In continuous HAART-using women, black
      women more rapidly died from AIDS or experienced incident ADI than their white
      counterparts after adjusting for confounders. Future studies examining behavioral
      and biologic factors in these women may further the understanding of HAART
      prognosis.

PMID- 24037211
TI  - Toll-like receptor variants are associated with infant HIV-1 acquisition and peak
      plasma HIV-1 RNA level.
AB  - OBJECTIVE: We evaluated the association of single nucleotide polymorphisms (SNPs)
      in TLRs with infant HIV-1 acquisition and viral control. DESIGN: Infant HIV-1
      outcomes were assessed in a Kenyan perinatal HIV-1 cohort. METHODS: Infants were
      genotyped for six candidate and 118 haplotype-tagging polymorphisms in TLRs 2, 3,
      4, 7, 8, and 9, MYD88 and TIRAP. Cox proportional hazards and linear regression
      were performed to assess associations with time to HIV-1 acquisition, time to
      infant mortality, and peak viral load. RESULTS: Among 368 infants, 56 (15%)
      acquired HIV-1 by month 1 and 17 (4.6%) between 1 and 12 months. Infants with the
      TLR9 1635A (rs352140) variant were more likely to acquire HIV-1 by 1 month
      [hazard ratio = 1.81, 95% confidence interval (CI) = 1.05-3.14, P = 0.033] and by
      12 months (hazard ratio = 1.62, CI = 1.01-2.60, P = 0.044) in dominant models
      adjusted for maternal plasma HIV-1 RNA level and genetic ancestry. Among 56
      infants infected at 1 month of age or less, at least one copy of the TLR9 1635A
      allele was associated with a 0.58 log10 copies/ml lower peak viral load (P =
      0.002). Female infants with at least one copy of the TLR8 1G (rs3764880) variant
      had a 0.78 log10 copies/ml higher peak viral load (P = 0.0009) and having at
      least one copy of the C allele for a haplotype tagging TLR7 variant (rs1634319)
      was associated with a 0.80 log10 copies/ml higher peak viral load in female
      infants (P = 0.0003). CONCLUSION: In this African perinatal cohort, we found
      several TLR polymorphisms associated with HIV-1 acquisition and progression.
      Defining mechanisms for these TLR associations may inform HIV-1 prevention
      strategies that leverage innate responses.

PMID- 24037212
TI  - CruzDB: software for annotation of genomic intervals with UCSC genome-browser
      database.
AB  - MOTIVATION: The biological significance of genomic features is often context
      dependent. Annotating a particular dataset with existing external data can
      provide insight into function. RESULTS: We present CruzDB, a fast and intuitive
      programmatic interface to the University of California, Santa Cruz (UCSC) genome
      browser that facilitates integrative analyses of diverse local and remotely
      hosted datasets. We showcase the syntax of CruzDB using microRNA binding sites as
      examples, and further demonstrate its utility with three biological discoveries.
      First, DNA replication timing is stratified in gene regions-exons tend to
      replicate early and introns late during S phase. Second, several non-coding
      variants associated with cognitive functions map to lincRNA transcripts of
      relevant function, suggesting potential function of these regulatory RNAs in
      neuronal diseases. Third, lamina-associated genomic regions are highly enriched
      in olfaction-related genes, indicating a role of nuclear organization in their
      regulation.

PMID- 24037213
TI  - Protein evolution along phylogenetic histories under structurally constrained
      substitution models.
AB  - MOTIVATION: Models of molecular evolution aim at describing the evolutionary
      processes at the molecular level. However, current models rarely incorporate
      information from protein structure. Conversely, structure-based models of protein
      evolution have not been commonly applied to simulate sequence evolution in a
      phylogenetic framework, and they often ignore relevant evolutionary processes
      such as recombination. A simulation evolutionary framework that integrates
      substitution models that account for protein structure stability should be able
      to generate more realistic in silico evolved proteins for a variety of purposes.
      RESULTS: We developed a method to simulate protein evolution that combines models
      of protein folding stability, such that the fitness depends on the stability of
      the native state both with respect to unfolding and misfolding, with phylogenetic
      histories that can be either specified by the user or simulated with the
      coalescent under complex evolutionary scenarios, including recombination,
      demographics and migration. We have implemented this framework in a computer
      program called ProteinEvolver. Remarkably, comparing these models with empirical
      amino acid replacement models, we found that the former produce amino acid
      distributions closer to distributions observed in real protein families, and
      proteins that are predicted to be more stable. Therefore, we conclude that
      evolutionary models that consider protein stability and realistic evolutionary
      histories constitute a better approximation of the real evolutionary process.

PMID- 24037214
TI  - Ontology-aware classification of tissue and cell-type signals in gene expression
      profiles across platforms and technologies.
AB  - MOTIVATION: Leveraging gene expression data through large-scale integrative
      analyses for multicellular organisms is challenging because most samples are not
      fully annotated to their tissue/cell-type of origin. A computational method to
      classify samples using their entire gene expression profiles is needed. Such a
      method must be applicable across thousands of independent studies, hundreds of
      gene expression technologies and hundreds of diverse human tissues and cell
      types. RESULTS: We present Unveiling RNA Sample Annotation (URSA) that leverages
      the complex tissue/cell-type relationships and simultaneously estimates the
      probabilities associated with hundreds of tissues/cell-types for any given gene
      expression profile. URSA provides accurate and intuitive probability values for
      expression profiles across independent studies and outperforms other methods,
      irrespective of data preprocessing techniques. Moreover, without re-training,
      URSA can be used to classify samples from diverse microarray platforms and even
      from next-generation sequencing technology. Finally, we provide a molecular
      interpretation for the tissue and cell-type models as the biological basis for
      URSA's classifications.

PMID- 24037215
TI  - Discovering combinatorial interactions in survival data.
AB  - MOTIVATION: Although several methods exist to relate high-dimensional gene
      expression data to various clinical phenotypes, finding combinations of features
      in such input remains a challenge, particularly when fitting complex statistical
      models such as those used for survival studies. RESULTS: Our proposed method
      builds on existing 'regularization path-following' techniques to produce
      regression models that can extract arbitrarily complex patterns of input features
      (such as gene combinations) from large-scale data that relate to a known clinical
      outcome. Through the use of the data's structure and itemset mining techniques,
      we are able to avoid combinatorial complexity issues typically encountered with
      such methods, and our algorithm performs in similar orders of duration as single
      variable versions. Applied to data from various clinical studies of cancer
      patient survival time, our method was able to produce a number of promising gene
      interaction candidates whose tumour-related roles appear confirmed by literature.

PMID- 24037216
TI  - Women's experience of abuse in a healthcare setting reveals preceding loss of
      power struggles, with sensitivity and dependency making them vulnerable to staff
      domination.

PMID- 24037217
TI  - The immunohistochemical expression of islet 1 and PAX8 by rectal neuroendocrine
      tumors should be taken into account in the differential diagnosis of metastatic
      neuroendocrine tumors of unknown primary origin.
AB  - Rectal neuroendocrine tumors (NETs) can be classified by histologic pattern and
      secretory products. Recently, rectal NETs have been noted to exhibit
      immunohistochemical (IHC) positivity for Islet 1 and PAX8, which are generally
      considered markers for NETs of pancreatic origin. In this study, we sought to
      characterize the IHC staining profile of rectal NETs and determine whether there
      was any correlation between the histologic pattern of rectal NETs and their IHC
      profile. Fifty-six primary rectal NETs were histologically reviewed and stained
      with antibodies against Islet 1, PAX8, CDX2, chromogranin A, and synaptophysin.
      In a subset of 31 cases, immunoreactivity for serotonin, pancreatic polypeptide
      (PP), and prostatic acid phosphatase (PAP) was also studied. By morphology, the
      tumors studied included 55 % trabecular, 27 % solid nested, 4 % acinar, and 14 %
      mixed patterns. Islet 1 was positive in 89 % and PAX8 in 79 % of cases. CDX2 was
      negative in all 56 cases. Cytoplasmic staining was observed for chromogranin A in
      30 % of cases and for synaptophysin in all 56 cases. Cytoplasmic staining for
      serotonin, PP, and PAP was present in 16, 61, and 97 % of cases, respectively.
      There was no correlation between histologic pattern and IHC staining pattern with
      any of the antibodies studied. We have demonstrated that Islet 1 and PAX8 are not
      entirely specific for NETs of pancreatic origin, as they are expressed in a
      majority of rectal NETs. Since rectal NETs may show an IHC staining profile which
      mirrors that of pancreatic NETs (Islet 1 and PAX8-positive, CDX2-negative), a
      metastatic rectal NET should be considered in the differential diagnosis and
      ruled out clinically in the work-up of a metastatic NET of unknown primary origin
      which exhibits this staining profile. 

PMID- 24037218
TI  - Dynamic aggregation of the mid-sized gadolinium complex {Ph4[Gd(DTTA)(H2O)2](
      )3}.
AB  - A compound binding three Gd(3+) ions, {Ph4[Gd(DTTA)(H2O)2](-) 3} (where H5DTTA is
      diethylenetriaminetetraacetic acid), has been synthesized around a hydrophobic
      center made up of four phenyl rings. In aqueous solution the molecules start to
      self-aggregate at concentrations well below 1 mM as shown by the increase of
      rotational correlation times and by the decrease of the translational self
      diffusion constant. NMR spectra recorded in aqueous solution of the diamagnetic
      analogue {Ph4[Y(DTTA)(H2O)2](-)3} show that the aggregation is dynamic and due to
      intermolecular pi-stacking interactions between the hydrophobic aromatic centers.
      From estimations of effective radii, it can be concluded that the aggregates are
      composed of two to three monomers. The paramagnetic {Ph4[Gd(DTTA)(H2O)2](-)3}
      exhibits concentration-dependent (1)H NMR relaxivities with high values of
      approximately 50 mM(-1) s(-1) (30 MHz, 25  degrees C) at gadolinium
      concentrations above 20 mM. A combined analysis of (1)H NMR dispersion profiles
      measured at different concentrations of the compound and (17)O NMR data measured
      at various temperatures was performed using different theoretical approaches. The
      fitted parameters showed that the increase in relaxivity with increasing
      concentration of the compound is due to slower global rotational motion and an
      increase of the Lipari-Szabo order parameter S(2).

PMID- 24037219
TI  - Advanced electron paramagnetic resonance on the catalytic iron-sulfur cluster
      bound to the CCG domain of heterodisulfide reductase and succinate: quinone
      reductase.
AB  - Heterodisulfide reductase (Hdr) is a key enzyme in the energy metabolism of
      methanogenic archaea. The enzyme catalyzes the reversible reduction of the
      heterodisulfide (CoM-S-S-CoB) to the thiol coenzymes M (CoM-SH) and B (CoB-SH).
      Cleavage of CoM-S-S-CoB at an unusual FeS cluster reveals unique substrate
      chemistry. The cluster is fixed by cysteines of two cysteine-rich CCG domain
      sequence motifs (CX31-39CCX35-36CXXC) of subunit HdrB of the Methanothermobacter
      marburgensis HdrABC complex. We report on Q-band (34 GHz) (57)Fe electron-nuclear
      double resonance (ENDOR) spectroscopic measurements on the oxidized form of the
      cluster found in HdrABC and in two other CCG-domain-containing proteins,
      recombinant HdrB of Hdr from M. marburgensis and recombinant SdhE of succinate:
      quinone reductase from Sulfolobus solfataricus P2. The spectra at 34 GHz show
      clearly improved resolution arising from the absence of proton resonances and
      polarization effects. Systematic spectral simulations of 34 GHz data combined
      with previous 9 GHz data allowed the unambiguous assignment of four (57)Fe
      hyperfine couplings to the cluster in all three proteins. (13)C Mims ENDOR
      spectra of labelled CoM-SH were consistent with the attachment of the substrate
      to the cluster in HdrABC, whereas in the other two proteins no substrate is
      present. (57)Fe resonances in all three systems revealed unusually large (57)Fe
      ENDOR hyperfine splitting as compared to known systems. The results infer that
      the cluster's unique magnetic properties arise from the CCG binding motif. 

PMID- 24037221
TI  - Design and testing of paramagnetic liposome-based CEST agents for MRI
      visualization of payload release on pH-induced and ultrasound stimulation.
AB  - The development of nanomedicines in cancer therapy is constantly growing because
      of the advantages associated with the use of nanosized drug delivery systems.
      Among them, the possibility of accurate spatiotemporal control of the release of
      the chemotherapeutic from the carrier is one of the most interesting and
      clinically relevant. To further improve the therapy outcome, the clinical
      translation of imaging protocols for the in vivo visualization of the release
      step is of paramount importance. In this work, the combination of the great
      chemical versatility of liposomes and the outstanding potential of MRI chemical
      exchange saturation transfer agents has been successfully harnessed to image the
      selective release of the liposomal content stimulated by endogenous (variation of
      pH) and externally applied (nonfocused ultrasound) stimuli. The use of clinically
      safe components (both liposomes and MRI agents) and the good results obtained in
      vitro hold promise for a successful future in vivo translation.

PMID- 24037220
TI  - Effects of distal mutation on the dynamic properties of carboxycytoglobin: a
      molecular dynamics simulation study.
AB  - Cytoglobin (Cgb) is a hexacoordinate globin that plays various physiological
      roles, including O2 transport, enzyme activity, and lipid peroxidation. The
      distal His(81)(E7) residue acts as the native sixth ligand and is crucial to
      exogenous ligand binding, distal environment adjustment, and heme pocket
      stabilization. The role of E7 has been widely studied in myoglobin, neuroglobin,
      and hemoglobin, but not in Cgb. In this work, the structural dynamic features of
      CO-ligated Cgb, CgbCO, as well as its three distal mutants H81QCgbCO, H81LCgbCO,
      and H81VCgbCO, were examined by performing molecular dynamics (MD) simulations.
      Results revealed that distal mutation significantly affected the dynamic
      properties of the CD-D-E and EF loop regions of Cgb. Distinct fluctuations and
      the occurrence of new inner cavities reflected rearrangements of the heme pocket.
      Distal mutation was found to affect heme motion slightly, indicating a different
      heme motion mechanism than that for neuroglobin. Some key residues such as E7 and
      CD3 showed remarkable changes in their dynamics that contributed to heme pocket
      rearrangement and loop region fluctuations. MD studies of four CgbCO models
      indicated that the distal E7 residue was a crucial influence on the dynamics of
      CgbCO in terms of loop fluctuations, cavity rearrangement, and slight heme
      motion. 

PMID- 24037222
TI  - The Green's function formalism as a bridge between single- and multi
      compartmental modeling.
AB  - Neurons are spatially extended structures that receive and process inputs on
      their dendrites. It is generally accepted that neuronal computations arise from
      the active integration of synaptic inputs along a dendrite between the input
      location and the location of spike generation in the axon initial segment.
      However, many application such as simulations of brain networks use point-neurons
      neurons without a morphological component-as computational units to keep the
      conceptual complexity and computational costs low. Inevitably, these applications
      thus omit a fundamental property of neuronal computation. In this work, we
      present an approach to model an artificial synapse that mimics dendritic
      processing without the need to explicitly simulate dendritic dynamics. The model
      synapse employs an analytic solution for the cable equation to compute the
      neuron's membrane potential following dendritic inputs. Green's function
      formalism is used to derive the closed version of the cable equation. We show
      that by using this synapse model, point-neurons can achieve results that were
      previously limited to the realms of multi-compartmental models. Moreover, a
      computational advantage is achieved when only a small number of simulated
      synapses impinge on a morphologically elaborate neuron. Opportunities and
      limitations are discussed.

PMID- 24037223
TI  - Structural evaluation and analyses of tumor differentiation factor.
AB  - Tumor differentiation factor (TDF) is a protein produced by the pituitary and
      secreted into the blood stream. The mechanism of its action has still not been
      elucidated, although the associated protein receptor was identified. Furthermore,
      the TDF protein does not have any homology with other known proteins, and the
      crystal structure of TDF also is not available at this time. To gain some insight
      into the structure of this rather underexplored protein, we have performed a
      molecular dynamics simulation of a model TDF structure. The structural stability
      of this protein is evaluated as a function of time. The time dependent structural
      changes of four cysteine residues present in this structure also are explored. 

PMID- 24037225
TI  - Can optimal drug dosing during ECMO improve outcomes?

PMID- 24037224
TI  - Subclinical cardiovascular disease and its association with risk factors in
      children with steroid-resistant nephrotic syndrome.
AB  - BACKGROUND: The aim of this study was to evaluate the presence of subclinical
      cardiovascular disease (CVD) and its relation to risk factors in pediatric
      patients with steroid-resistant nephrotic syndrome (NS). METHODS: Thirty-seven
      patients with normal renal function were compared with 22 healthy controls
      regarding the presence of subclinical CVD. Measurements included aortic pulse
      wave velocity (PWV), carotid intima media thickness (IMT), and left ventricular
      mass (LVM). Patients were additionally assessed for blood pressure (BP) pattern
      and the presence of hypertension by 24-h ambulatory blood pressure monitoring.
      RESULTS: Compared with the controls, patients had significantly higher mean
      aortic PWV-standard deviation scores (SDS), mean carotid IMT-SDS, and LVM index
      (p < 0.001 for all). Increased aortic PWV was noted in 5 % of patients, increased
      carotid IMT in 22 %, and increased LVM index in 19 %. Five patients (14 %) were
      hypertensive, and mean BP indexes, SDS, and BP loads during nighttime were
      significantly higher than those during daytime (p < 0.001 for all). Multivariate
      analysis revealed a significant relationship between PWV-SDS and ferritin (R(2) =
      0.269, p = 0.006) and between carotid IMT-SDS and proteinuria (R(2) = 0.141, p =
      0.022). The LVM index was independently associated only with higher body mass
      index SDS (R(2) = 0.317, p < 0.001). In addition, six patients (16 %) had
      multiple abnormal subclinical CVD markers, and increased subclinical CVD risk was
      independently associated only with higher low-density lipoprotein cholesterol
      (R(2) = 0.292, p = 0.044). CONCLUSIONS: Based on these results, steroid-resistant
      NS children generally are at high risk of cardiovascular complications, but the
      increased risk is likely to be multifactorial.

PMID- 24037226
TI  - Effects of hydroxyethyl starch in subgroups of patients with severe sepsis:
      exploratory post-hoc analyses of a randomised trial.
AB  - PURPOSE: It has been speculated that certain subgroups of sepsis patients may
      benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in
      the earlier resuscitation of patients with more severely impaired circulation.
      METHODS: This was a post-hoc, subgroup analysis of all 798 patients with severe
      sepsis randomised in the 6S trial according to time from ICU admission to
      randomisation, surgery and fluids given prior to randomisation and markers of
      shock at randomisation. Intervention effects estimated as risk ratios were
      analysed between the HES versus Ringer's acetate groups to detect subgroup
      heterogeneity of the effects on 90-day mortality. Multiple logistic regression
      was used to adjust for risk factors. RESULTS: Most baseline characteristics were
      comparable between the HES and Ringer's acetate groups in the different
      subgroups. There was no heterogeneity in the intervention effect on 90-day
      mortality in the following subgroups: randomisation earlier than 4 h after ICU
      admission versus later (test of interaction P = 0.85), surgery versus no surgery
      (P = 0.42), colloids given versus not given (P = 0.57), <2 l of crystalloids
      given prior to randomisation vs. >2 l (P = 0.88) or plasma lactate >4 mmol/l
      versus <4 mmol/l (P = 0.54), hypotension versus no hypotension (P = 0.32) or use
      of vasopressor or inotropic agents at randomisation versus no use (P = 0.10).
      CONCLUSIONS: The increased 90-day mortality observed in patients with severe
      sepsis resuscitated with HES 130/0.42 did not appear to depend on time course,
      surgery or fluids given prior to randomisation or on markers of shock at
      randomisation. As the analyses were planned post hoc and their power is reduced,
      the results should be interpreted with caution.

PMID- 24037227
TI  - Spatial characterization of bark beetle infestations by a multidate synergy of
      SPOT and Landsat imagery.
AB  - Biological infestations in forests, e.g. the insect outbreaks, have been shown as
      favoured by future climate change trends. In Europe, the European spruce bark
      beetle (Ips typographus L.) is one of the main agents causing substantial
      economic disturbances in forests. Therefore, studies on spatio-temporal
      characterization of the area affected by bark beetle are of major importance for
      rapid post-attack management. We aimed at spatially detecting damage classes by
      combining multidate remote sensing data and a non-parametric classification. As
      study site served a part of the Bavarian Forest National Park (Germany). For the
      analysis, we used 10 geometrically rectified scenes of Landsat and SPOT sensors
      in the period between 2001 and 2011. The main objective was to explore the
      potential of medium-resolution data for classifying the attacked areas. A further
      aim was to explore if the temporally adjacent infested areas are able to be
      separated. The random forest (RF) model was applied using the reference data
      drawn from high-resolution aerial imagery. The results indicate that the
      sufficiently large patches of visually identifiable damage classes can be
      accurately separated from non-attacked areas. In contrast to those, the other
      mortality classes (current year, current year 1 and current year 2 infested
      classes) were mostly classified with higher commission or omission errors as well
      as higher classification biases. The available medium-resolution satellite
      images, combined with properly acquired reference data, are concluded to be
      adequate tools to map area-based infestations at advanced stages. However, the
      quality of reference data, the size of infested patches and the spectral
      resolution of remotely sensed data are the decisive factors in case of smaller
      areas. Further attempts using auxiliary height information and spatially enhanced
      data may refine such an approach. 

PMID- 24037228
TI  - Characterization of groundwater quality in three settlement areas of Enugu
      metropolis, southeastern Nigeria, using multivariate analysis.
AB  - Groundwater quality of Enugu metropolis comprising Achara Layout, Abakpa, and
      Emene settlement areas has been studied and characterized using multivariate
      statistical techniques. Three principal components (PCs) which explain 77.93 and
      88.17% were extracted at Achara Layout and Abakpa, respectively, while two PCs
      which explain 83.13% were extracted at Emene. PC 1 of all the three areas
      reflects weathering of the host rock minerals and constitutes the dominant
      controlling process for all the areas. PC 2 of the three areas and PC 3 of Achara
      Layout and Abakpa can be attributed to both weathering/leaching of feldspathic
      minerals of host rocks (giving rise to alkaline earth metals in the groundwater)
      and anthropogenic activities. Cluster analysis defined groups of groundwater
      samples with similar hydrochemical characteristics. Two groups in Achara Layout
      and Emene fell into the high pollution loading class, while only one group in
      Abakpa fell into this class. The variation in the groundwater quality within each
      of the three areas may be explained in terms of groundwater flow directions, land
      use, and well depths. Discriminant analysis showed that the discriminating
      parameters of the groundwater quality of Achara Layout, Abakpa, and Emene are
      total dissolved solids, Na and Mg, and Cl, respectively. This study has revealed
      that the groundwater quality of the areas is controlled by both geogenic and
      anthropogenic processes and activities. The generated groundwater quality spatial
      variation models for each area will serve as a tool in the planning and
      development of groundwater in that region.

PMID- 24037229
TI  - Births in captive stump-tailed macaques (Macaca arctoides).
AB  - In this report, nighttime births of 3 stump-tailed macaques observed at the
      Aizawl Zoological Park, India, are described. Continuous focal observations were
      collected a long with video and still photographs, on the 3 parturitions, from
      the first observed onset of labour. The average time taken for infant birth,
      beginning with visibility of the head at the vaginal opening, was 45 s. The
      births observed were similar in many respects, regardless of parity and social
      context. The average time taken for consuming the placenta was 4 min 4 s and the
      average number of contractions was 6.3. In all cases births occurred with the
      infant emerging in the occiput posterior position, assisted by the mother.
      Individual variations existed in the number of contractions, intercontraction
      intervals, self-examination of the anogenital region, duration of labour and the
      interval between infant birth and the delivery of the placenta. Each mother
      ingested the placenta completely, while holding her neonate, but without paying
      much attention to the neonate during placentophagia. Placentophagia appears to
      provide nutrition to the mothers. Detailed data on parturition in non-human
      primates, and particularly for Macacaarctoides , are still scarce. Data, such as
      those presented here, contribute to our understanding of primate birth and the
      adaptive pressures that shape parturition behaviour and reproductive success.

PMID- 24037230
TI  - Heterolytic H2 activation on a carbene-ligated rhodathiaborane promoted by
      isonido-nido cage opening.
AB  - A new mechanism of H2 activation is reported to occur on a carbene-ligated
      rhodathiaborane that features metal-thiaborane bifunctional synergistic effects.
      The key is the creation of vacant coordination sites by an isonido-nido
      structural transformation leading to the heterolytic H-H bond splitting. 

PMID- 24037231
TI  - Long-term outcomes of pars plana vitrectomy without internal limiting membrane
      peeling for optic disc pit maculopathy.
AB  - PURPOSE: To evaluate the results of surgical treatment of maculopathy secondary
      to congenital optic pit anomaly with pars plana vitrectomy (PPV), endolaser to
      the temporal edge of the optic disc and C3F8 tamponade without internal limiting
      membrane (ILM) peeling. PATIENTS AND METHODS: Thirteen eyes of 12 patients with
      serous macular detachment and/or macular retinoschisis secondary to congenital
      optic disc pit (ODP) were included in the study. All eyes underwent PPV,
      posterior hyaloid removal, endolaser photocoagulation on the temporal margin of
      the optic disc and 12% C3F8 gas tamponade. Anatomic success and functional
      outcome determined retrospectively by optical coherence tomography and
      measurement of best corrected visual acuity (BCVA), respectively were the main
      outcome parameters. RESULTS: Two lines or more improvement in BCVA was obtained
      in 11 eyes and 6 of these eyes had 20/40 or better BCVA at the final visit.
      Subretinal or intraretinal fluid was completely resorbed postoperatively in 12
      eyes but a little intraretinal fluid persisted in one eye at the 16-month follow
      up. Better visual improvement was observed in patients treated by earlier
      surgical intervention. CONCLUSION: PPV, C3F8 gas tamponade and endolaser to the
      optic disc margin without ILM peeling may yield favourable results in the
      treatment of ODP maculopathy.

PMID- 24037232
TI  - Refractive errors in a rural Korean adult population: the Namil Study.
AB  - PURPOSE: To assess the prevalence of refractive errors, including myopia, high
      myopia, hyperopia, astigmatism, and anisometropia, in rural adult Koreans.
      METHODS: We identified 2027 residents aged 40 years or older in Namil-myeon, a
      rural town in central South Korea. Of 1928 eligible residents, 1532 subjects
      (79.5%) participated. Each subject underwent screening examinations including
      autorefractometry, corneal curvature measurement, and best-corrected visual
      acuity. RESULTS: Data from 1215 phakic right eyes were analyzed. The prevalence
      of myopia (spherical equivalent (SE) <-0.5 diopters (D)) was 20.5% (95%
      confidence interval (CI): 18.2-22.8%), of high myopia (SE <-6.0 D) was 1.0% (95%
      CI: 0.4-1.5%), of hyperopia (SE>+0.5 D) was 41.8% (95% CI: 38.9-44.4%), of
      astigmatism (cylinder <-0.5 D) was 63.7% (95% CI: 61.0-66.4%), and of
      anisometropia (difference in SE between eyes >1.0 D) was 13.8% (95% CI: 11.9
      15.8%). Myopia prevalence decreased with age and tended to transition into
      hyperopia with age up to 60-69 years. In subjects older than this, the trend in
      SE refractive errors reversed with age. The prevalence of astigmatism and
      anisometropia increased consistently with age. The refractive status was not
      significantly different between males and females. CONCLUSIONS: The prevalence of
      myopia and hyperopia in rural adult Koreans was similar to that of rural Chinese.
      The prevalence of high myopia was lower in this Korean sample than in other East
      Asian populations, and astigmatism was the most frequently occurring refractive
      error.

PMID- 24037233
TI  - Evaluation of retinal nerve fiber layer and ganglion cell complex thickness after
      ocular blunt trauma.
AB  - PURPOSE: To evaluate circumpapillary retinal nerve fiber layer (cpRNFL) and
      ganglion cell complex (GCC) after ocular blunt trauma. METHODS: Best-corrected
      visual acuity (BCVA), cpRNFL and GCC were evaluated by RTVue-100 OCT in all
      consecutive patients with previous monocular blunt trauma seen between January
      2012 and December 2012. RESULTS: Twenty-two patients (11 females, 11 males, mean
      age 43.9 +/- 14.2 years) were included in the study. Patients were seen after a
      mean of 8.42 +/- 13.3 (range, 0.08-55.3) years from ocular blunt trauma. BCVA was
      normal in 11 cases and was less than 0.4 LogMAR in all cases. In 9/22 patients
      (40.9%), cpRNFL and GCC were reduced, whereas in one case an isolated reduction
      of GCC with normal cpRNFL was present. In patients with reduction of cpRNFL and
      GCC, mean BCVA was 0.17 +/- 0.17 LogMAR. In 6/9 patients (66.6%) with cpRNFL and
      GCC reduction, BCVA was <= 0.1 LogMAR. CONCLUSION: cpRNFL and GCC reduction may
      be present after ocular blunt trauma and may be associated with preserved visual
      acuity.

PMID- 24037234
TI  - Optical coherence tomography findings in spinocerebellar ataxia-3.
AB  - PURPOSE: To report optical coherence tomography (OCT) findings in order to detect
      subclinical alterations of the afferent visual pathways in spinocerebellar ataxia
      3 (SCA-3). PATIENTS AND METHODS: Nine genetically confirmed patients (18 eyes)
      were evaluated with a complete ophthalmologic examination including visual
      acuity, colour vision, visual field test, and retinal nerve fibre layer (RNFL)
      and macular thickness with OCT Cirrus HD. A neurological examination was
      performed and the Scale for the Assessment and Rating of Ataxia (SARA score) was
      determined in all patients. RESULTS: The mean RNFL thickness was 77.39 microns,
      standard deviation (SD) was +/- 5.93. In 15 eyes (83.33%), the mean RNFL
      thickness was lower than the population average considering age and sex. In 10
      cases, there was a reduction of the RNFL thickness in the superior sector, eight
      in the inferior and four in the nasal. Temporal sector RNFL thickness was
      preserved in all eyes. RNFL thickness was inversely correlated to SARA score (r=
      0.64, P=0.012). The mean macular thickness was 252.61 microns, SD +/- 22.80,
      being inferior respecting average population in only two eyes (11.11%). In four
      patients, (eight eyes) OCT studies were performed during a mean follow-up of
      14.25 months, and in five eyes (62.50%) there was a mild trend to a RNFL
      thickness decrease in this period. CONCLUSION: A mild and progressive decrease in
      RNFL thickness can be observed in SCA-3 patients. A negative correlation exists
      between an anatomic marker (RNFL thickness) and a clinical severity scale (SARA
      score); thus, RNFL thickness could be considered as a promising biomarker of the
      disease.

PMID- 24037236
TI  - Bimanual anterior segment revision surgery for anterior capsule contraction
      syndrome associated with anterior flexion of intraocular lens haptics.
AB  - PURPOSE: To report the incidence of anterior capsule contraction syndrome (ACCS)
      and to present a novel minimally invasive bimanual technique for anterior segment
      revision surgery associated with ACCS with anterior flexion of the intraocular
      lens haptics. METHODS: A consecutive cohort of 268 eyes of 161 patients
      undergoing phacoemulsification and implantation of the same type of hydrophilic
      acrylic aspheric intraocular lens cohort were analysed and a novel technique of
      minimally invasive bimanual technique for anterior segment revision surgery is
      described. RESULTS: We identified four eyes (1.5%) of three patients with
      advanced ACCS. Successful restoration of a clear visual axis with minimal
      induction of astigmatism and rapid visual rehabilitation was achieved in all four
      cases. CONCLUSION: This technique is a safe and minimally invasive alternative to
      laser or vitrector-cut capsulotomy to restore a clear visual axis. In cases of
      advanced ACCS, it offers the option for haptic reposition or amputation.

PMID- 24037235
TI  - Intravitreal bevacizumab for proliferative diabetic retinopathy with new dense
      vitreous hemorrhage after full panretinal photocoagulation.
AB  - PURPOSE: To evaluate the efficacy and safety of intravitreal bevacizumab (IVB)
      injections for the treatment of proliferative diabetic retinopathy (PDR) with new
      dense vitreous hemorrhage (VH) after previous full panretinal photocoagulation
      (PRP). METHODS: Prospective study of consecutive PDR with prior complete PRP
      patients, who presented with new dense VH, were treated with IVB injection.
      Complete ophthalmic examination and/or ocular ultrasonography were performed at
      baseline and 1, 6, and 12 weeks and 6, 9, and 12 months after the first
      injection. Reinjection was done in non-clearing and recurrent VH. RESULTS:
      Eighteen eyes of 18 patients, mean age 47.7 +/- 12.69 years were included. In
      all, 14 (77.78%) patients had type 2 diabetes mellitus. Systemic hypertension and
      dyslipidemia were the most common systemic diseases. All cases were phakic eye
      with previous complete PRP. Patients received 1.6 +/- 0.42 intravitreal
      injections over a 12-month period. VH cleared completely in 7 (38.89%), 9 (50%),
      and 13 (72.22%) eyes after 6 weeks, 6 months, and 12 months, respectively. Re
      bleeding, however, occurred in 10 (56%) eyes during the follow-up period, and 5
      (28%) eyes still had residual VH at the last visit. Statistically significant
      visual gain was observed in 9 (50%) eyes. Unfortunately, 2 (11%) eyes had severe
      visual loss because of the tractional retinal detachment (TRD). Mild ocular
      complication was detected in one patient. CONCLUSION: IVB injection had good
      efficacy and safety for treatment of new VH in patients with PDR and prior
      complete PRP. This procedure may be especially relevant for diabetic patients at
      high-risk for surgical intervention.

PMID- 24037237
TI  - Behcet's disease-like symptoms associated with myelodysplastic syndrome with
      trisomy 8: a case report and review of the literature.

PMID- 24037238
TI  - The influence of stimulus phase duration on discomfort and electrically induced
      torque of quadriceps femoris.
AB  - BACKGROUND: Although a number of studies have compared the influence of different
      electrical pulse parameters on maximum electrically induced torque (MEIT) and
      discomfort, the role of phase duration has been poorly investigated. OBJECTIVE:
      To examine the variation in muscle torque and discomfort produced when
      electrically stimulating quadriceps femoris using pulsed current with three
      different phase durations in order to establish whether there are any advantages
      or disadvantages in varying the phase duration over the range examined. METHOD:
      This is a two repeated-measures, within-subject study conducted in a research
      laboratory. The study was divided into 2 parts with 19 healthy young adults in
      each part.In part 1, MEIT was determined for each phase duration (400, 700, and
      1000 us), using a biphasic pulsed current at a frequency of 50 Hz. In part 2,
      stimulus amplitude was increased until the contractions reached 40% of maximum
      voluntary isometric contraction (MVIC) and the associated discomfort produced by
      each phase duration was measured. RESULTS: In part 1 of the study, we found that
      the average MEITs generated with each phase duration (400, 700, and 1000 us) were
      55.0, 56.3, and 58.0% of MVIC respectively, but the differences were not
      statistically significant (p=.45). In part 2, we found a statistically
      significant increase in discomfort over the same range of phase durations. The
      results indicate that, for a given level of torque production, discomfort
      increases with increasing phase duration (p=.008). CONCLUSIONS: Greater muscle
      torque cannot be produced by increasing the stimulus phase duration over the
      range examined. Greater discomfort is produced by increasing the stimulus phase
      duration.

PMID- 24037239
TI  - The Brazilian version of the SRS-22r questionnaire for idiopathic scoliosis.
AB  - BACKGROUND: The SRS-22r questionnaire is a well-accepted instrument used to
      measure health-related quality of life in patients with idiopathic scoliosis. No
      validated tool exists in Brazil for idiopathic scoliosis, and the use of the SRS
      22r in non-English Laguage contries requires its transcultural adaptation.
      OBJECTIVE: The objective of this study was to culturally adapt the translated
      Brazilian version of the SRS-22r questionnaire and to determine its reliability
      using statistical tests for internal consistency and test-retest reliability.
      METHOD: The transcultural adaptation process was carried out according to the
      recommendations of the American Academy of Orthopedic Surgeons. The pre-final
      version was administered to 44 patients with idiopathic scoliosis. The mean age
      of the participants was 18.93 years and the mean curve magnitude was 54.6 degrees
      . A subgroup of 30 volunteers completed the questionnaire a second time one week
      later to determine the scale's reproducibility. Internal consistency was
      determined using Cronbach's alpha coefficient, and the test-retest reliability
      was determined using the Intraclass Correlation Coefficient (ICC). RESULTS: No
      floor effects were observed using the Brazilian version of the SRS-22r. Ceiling
      effects were observed in the Pain and Satisfaction with Management domains. The
      internal consistency values were very good for 3 domains and good for 2 domains.
      The ICC values were excellent for all domains. CONCLUSIONS: The high values of
      internal consistency and ICC reproducibility suggest that this version of the
      questionnaire can be used in Brazilian patients with idiopathic scoliosis.

PMID- 24037240
TI  - Relationship between body balance, lung function, nutritional status and
      functional capacity in adults with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) is a hereditary condition in which lung disease
      affects all patients. In addition to pulmonary involvement, the multisystemic
      components of CF cause significant physical limitations. However, the impact of
      lung function on balance control in CF has not been studied. OBJECTIVE: To assess
      body balance in adults with CF and to test its possible associations with lung
      function, nutritional status, and functional capacity. METHOD: This was a cross
      sectional study in which 14 adults with CF underwent pulmonary function testing
      (spirometry, body plethysmography, and carbon monoxide diffusing capacity (DLco),
      respiratory muscle strength, 6-min walking distance (6MWD), Berg balance scale
      (BBS), nutritional analysis (body mass index and bioelectrical impedance), and
      stabilometry. Body balance was quantified using stabilometry; all participants
      performed the following two trials: opened base, eyes open (OBEO); closed base,
      eyes closed (CBEC). RESULTS: In stabilometry, the median for the lateral range
      and anterior-posterior range in the CBEC trial was 0.10 (0.08-0.11) and 0.13
      (0.11-0.22), respectively (p<0.05). The maximal inspiratory pressure (MIP)
      correlated inversely with the lateral standard deviation (rho=-0.61; p<0.05) as
      the DLco correlated positively with the anterior-posterior range (rho=0.54;
      p<0.05). There were significant relationships between body composition indexes
      and almost all stabilometric variables measured. There were no relationships of
      the BBS and 6MWD with the stabilometric variables. CONCLUSIONS: In adults with
      CF, imbalance occurs mainly in the anterior-posterior direction and is especially
      associated with body composition.

PMID- 24037241
TI  - Relationship of musculoskeletal pain with physical and functional variables and
      with postural changes in school children from 6 to 12 years of age.
AB  - BACKGROUND: Painful disorders can affect children and adolescents, causing
      distress and significant demand for health services. OBJECTIVE: To identify the
      prevalence of musculoskeletal pain and its relation to age, sex, body mass index
      (BMI), how to carry school supplies, postures used in ADLs, outside school
      physical exercises and postural changes in students. METHOD: Cross-sectional
      exploratory study with a convenience sample consisted of 262 schoolchildren aged
      6 to 12 years (137 female). Data collection was conducted by questionnaire
      containing personal data, presence and location of pain, means of transportation
      and illustrative figures for choosing the way of carrying school supplies and
      postures ADL's. Postural evaluation was performed by observational analysis and
      body mass index calculated from information on height, weight, age and sex.
      Descriptive analysis was carried out with numbers and percentages. For
      inferential statistics, comparison of average age according to the presence of
      pain was performed by Kruskal-Wallis with Dunn's post-test. Categorical variables
      were compared with chi-square test. RESULTS: The presence of musculoskeletal pain
      was reported by 51.1% of the students and 38.93% had pain in only one region. The
      most affected regions were legs, spine, arms and shoulders. The pain increased
      with age and with physical activity. CONCLUSIONS: In the our sample, 51.1% of
      students reported pain and 38.93% reported pain in only one region. There was no
      association between the presence of pain and sex, BMI, how to carry school
      supplies, postures used in ADLs and postural changes. The increasing age and
      physical exercise influenced significantly the presence of pain.

PMID- 24037242
TI  - Network-based stratification of tumor mutations.
AB  - Many forms of cancer have multiple subtypes with different causes and clinical
      outcomes. Somatic tumor genome sequences provide a rich new source of data for
      uncovering these subtypes but have proven difficult to compare, as two tumors
      rarely share the same mutations. Here we introduce network-based stratification
      (NBS), a method to integrate somatic tumor genomes with gene networks. This
      approach allows for stratification of cancer into informative subtypes by
      clustering together patients with mutations in similar network regions. We
      demonstrate NBS in ovarian, uterine and lung cancer cohorts from The Cancer
      Genome Atlas. For each tissue, NBS identifies subtypes that are predictive of
      clinical outcomes such as patient survival, response to therapy or tumor
      histology. We identify network regions characteristic of each subtype and show
      how mutation-derived subtypes can be used to train an mRNA expression signature,
      which provides similar information in the absence of DNA sequence. 

PMID- 24037243
TI  - TCPA: a resource for cancer functional proteomics data.

PMID- 24037244
TI  - IntOGen-mutations identifies cancer drivers across tumor types.
AB  - The IntOGen-mutations platform (http://www.intogen.org/mutations/) summarizes
      somatic mutations, genes and pathways involved in tumorigenesis. It identifies
      and visualizes cancer drivers, analyzing 4,623 exomes from 13 cancer sites. It
      provides support to cancer researchers, aids the identification of drivers across
      tumor cohorts and helps rank mutations for better clinical decision-making. 

PMID- 24037245
TI  - Exploiting tertiary structure through local folds for crystallographic phasing.
AB  - We describe an algorithm for phasing protein crystal X-ray diffraction data that
      identifies, retrieves, refines and exploits general tertiary structural
      information from small fragments available in the Protein Data Bank. The
      algorithm successfully phased, through unspecific molecular replacement combined
      with density modification, all-helical, mixed alpha-beta, and all-beta protein
      structures. The method is available as a software implementation: Borges. 

PMID- 24037246
TI  - Mouth care to reduce ventilator-associated pneumonia.
AB  - OVERVIEW: Despite the well-established association between good oral hygiene and
      the prevention of ventilator-associated pneumonia (VAP), the importance of mouth
      care in infection control is seldom recognized. The authors discuss the
      pathophysiology of VAP and why oral care is crucial to its prevention. They also
      provide an evidence-based, step-by-step guide to providing optimal oral care for
      intubated patients.

PMID- 24037247
TI  - Decreasing patient agitation using individualized therapeutic activities.
AB  - OVERVIEW: Hospitalized patients who are suffering from cognitive impairment,
      delirium, suicidal ideation, traumatic brain injury, or another behavior-altering
      condition are often placed under continuous observation by designated "sitters."
      These patients may become agitated, which can jeopardize their safety even when a
      sitter is present. This quality improvement project was based on the hypothesis
      that agitation can be decreased by engaging these patients in individualized
      therapeutic activities. The authors created a tool that allowed continuous
      observers to identify a patient's abilities and interests, and then offer such
      activities to the patient. Data were collected using a scale that measured
      patient agitation before, during, and after these activities. The authors found
      that during the activities, 73% of patients had decreased levels of agitation
      compared with baseline, and 64% remained less agitated for at least one hour
      afterward.The intervention appeared effective in reducing levels of agitation in
      selected patients who were receiving continuous observation on nonpsychiatric
      units at a large, urban level 1 trauma center. Many patients expressed gratitude
      for the diversion from their health issues. Further investigation into the
      effectiveness of this intervention and its impact on the use of medications or
      restraints is warranted.

PMID- 24037248
TI  - Predictors of 30-day readmission after subarachnoid hemorrhage.
AB  - BACKGROUND: Readmission within 30 days is increasingly evaluated as a measure of
      quality of care. There are few data on the rates of readmission after
      subarachnoid hemorrhage (SAH). OBJECTIVE: We sought to determine the predictors
      of 30-day readmission in patients with SAH. METHODS: We prospectively identified
      283 patients with SAH admitted between 2006 and 2012. Readmission was determined
      by means of an automated query with confirmation in the electronic medical
      record. RESULTS: Overall, 21 (8 %) patients were readmitted for infection (n =
      8), headache (n = 5), hydrocephalus (n = 4), cardiovascular causes (n = 2),
      medication-related complications (n = 1), and cerebral ischemia (n = 1).
      Readmission was associated with longer intensive care unit (ICU) length of stay
      (LOS) (15.4 [13.4-19.3] vs. 12.2 [8.2-18.5] days, P = 0.02), hospital LOS (22.2
      [17.4-23.0] vs. 16.8 [12.0-24.1] days, P = 0.01), and placement of an external
      ventricular drain (EVD, OR 3.9, 95 % CI 1.3-12.0, P = 0.01). Readmission was not
      associated with admission neurologic grade, NIH Stroke scale at 14 days, modified
      Rankin scale at 3 months, history of cardiovascular disease, or radiographic
      cerebral infarction (P > 0.1). CONCLUSIONS: Demographics, severity of neurologic
      injury, radiographic cerebral infarction, and outcomes were not associated with
      readmission after SAH. Markers of a more complicated hospital course (ICU and
      hospital LOS, EVD placement) were associated with 30-day readmission. Most
      readmissions were for infections acquired after discharge. Readmission within 30
      days is difficult to predict, and, since the most common reason was infection
      acquired after discharge, it may be difficult to prevent without an integrated
      health system and coordinated care.

PMID- 24037249
TI  - HIV prevalence and risk behaviours among people who inject drugs in Iran: the
      2010 National Surveillance Survey.
AB  - OBJECTIVES: To assess the prevalence of HIV and related risk behaviours among
      people who inject drugs (PWID) in Iran. METHODS: We conducted a national cross
      sectional bio-behavioural surveillance survey between March and July 2010,
      interviewing male PWID from a geographically dispersed sample through a facility
      based sampling method. RESULTS: We recruited 2480, and tested 2290 PWID. The
      overall prevalence of HIV was 15.2% (95% CI 9.7% to 23.1%). Among those who had
      injected drugs over the last month, 36.9% had used a non-sterile needle, and
      12.6% had practiced shared injection. Over the past 12 months preceding the
      interview, 30.4% had sold sex for money, drugs, goods or a favour. In the
      multivariate analysis, the prevalence of HIV had a positive association with age,
      while having above high school education, and permanent job were protective.
      CONCLUSIONS: Unsafe injection, and sexual risk behaviours are still frequent and
      the prevalence of HIV among PWID remains high. Intensified efforts are needed to
      prevent the further spread of HIV among Iranian PWID and their sexual partners.

PMID- 24037250
TI  - Is imaging the future of axillary staging in breast cancer?
AB  - Axillary management in patients with breast cancer has become much less invasive
      with the introduction of sentinel lymph node biopsy (SLNB). However, over 70 % of
      SLNBs are negative, questioning the generic use of this invasive procedure.
      Emerging evidence indicates that breast cancer patients with a low axillary
      burden of disease do not benefit from axillary lymph node dissection (ALND). Non
      invasive techniques such as paramagnetic iron oxide contrast-enhanced magnetic
      resonance imaging (MRI) may provide genuine alternatives to axillary staging and
      should be evaluated within clinical trials. Selective axillary surgery could then
      be offered based on imaging findings and for therapeutic intent. This non
      operative approach would reduce morbidity further and facilitate interpretation
      of follow-up imaging. Key Points * Modern imaging and biopsy greatly help the
      axillary staging of breast cancer. * Superparamagnetic iron oxide (SPIO)-enhanced
      MRI offers a further advance. * Sentinel lymph node biopsy may become redundant
      with SPIO-enhanced MRI. * Selective therapeutic axillary surgery should be based
      upon preoperative imaging findings. 

PMID- 24037251
TI  - A pyridine-functionalized pyrazolinofullerene used as a buffer layer in polymer
      solar cells.
AB  - A pyridine-functionalized pyrazolinofullerene (1) was synthesized in 42% yield
      via an improved one-pot reaction of C60, 3,6-di(2-pyridyl)-1,2,4,5-tetrazine, and
      water. The structure of 1 was unambiguously determined by X-ray diffraction of
      its single crystal. Due to the coordination capability of the functional groups
      on fullerene, compound 1 was used as a buffer layer to modify ZnO in inverted
      polymer solar cells. The power conversion efficiency was improved from 3.65% to
      4.18% for inverted P3HT:PC61BM solar cells.

PMID- 24037252
TI  - Innovations in minimally invasive surgery: lessons learned from translational
      animal models.
AB  - PURPOSE: Animal models are key elements of surgical research and promotion of new
      techniques. Inanimate models, anatomical specimens, and living animals are all
      necessary to solve the various problems encountered by the advent of a new
      surgical technique. The development of Natural Orifice Transluminal Endoscopic
      Surgery (NOTES) procedures is a representative model. METHODS: Over 400
      experimental procedures were performed in inanimate models, ex vivo tissues and
      animals to solve all problems faced by the development of NOTES surgery:
      peritoneal access, gastrotomy closure, exposure, retraction, dissection as well
      as education to start this new procedure. RESULTS: The successive use of all
      models allows to identify the ideal solution for each problem and to precisely
      define the safest and most reliable option to apply the new technique in
      patients. It allowed to perform the first transvaginal and transgastric
      cholecystectomy in patients in a safe way. CONCLUSION: Animal experimentation
      remains necessary as even sophisticated computer-based solutions are unable to
      model all interactions between molecules, cells, tissues, organisms, and their
      environment. Animal research is required in many areas to validate new
      technologies, develop training, let alone its major goal (namely to avoid using
      patients for experimentation) which is to be the first "model" for the surgeon.

PMID- 24037253
TI  - Chronic complaints after simple sutured repair for umbilical or epigastric
      hernias may be related to recurrence.
AB  - PURPOSE: Umbilical and epigastric hernia repairs are minor, but are commonly
      conducted surgical procedures. Long-term results have only been sparsely
      investigated. Our objective was to investigate the risk of chronic complaints
      after a simple sutured repair for small umbilical and epigastric hernias.
      METHODS: A retrospective cohort study with a 5-year questionnaire and clinical
      follow-up was conducted. Patients undergoing primary elective, open non-mesh
      umbilical or epigastric sutured hernia repair were included. Patients completed a
      structured questionnaire regarding chronic complaints during work and leisure
      activities using a verbal rating scale. The primary outcome was chronic
      complaints. RESULTS: A total of 295 patients were included for analysis after a
      median of 5.0-year (range 2.8-8.0) follow-up period. Follow-up results were
      achieved from 262 of the included patients (90 % response rate). Up till 5.8 % of
      the patients reported moderate or severe pain and discomfort. Work and leisure
      activities were restricted in 8.5 and 10.0 % of patients, respectively. Patients
      with chronic complaints had a higher incidence of recurrence (clinical and
      reoperation), than patients with none or mild complaints (78.6 vs. 22.2 % (P <
      0.001)). The recurrence rate was significantly higher after a repair with
      absorbable suture (20.1 %) compared with non-absorbable suture repair (4.2 %) (P
      < 0.001). CONCLUSION: We found that chronic complaints after a simple sutured
      umbilical or epigastric repair was in the level of 5.5 % and could in part be
      explained by recurrence. Furthermore, absorbable suture should be omitted to
      reduce risk of recurrence.

PMID- 24037254
TI  - Dual antiplatelet therapy dilemmas: duration and choice of antiplatelets in acute
      coronary syndromes.
AB  - Dual antiplatelet therapy (DAPT) is a key component of therapy for acute coronary
      syndromes managed with and without percutaneous coronary intervention. Recent
      advances have given patients a wider variety of therapeutic options including the
      use of combinations of agents, dosing strategies, and durations of therapy. The
      optimal regimen minimizes thrombotic risk without increasing the risk of
      bleeding. Choosing the best therapy for each patient is an individualized dilemma
      that requires new, evidence-based tools to support regimen decision-making. 

PMID- 24037255
TI  - [Quality and appropriateness of pain medication. Instrument for estimation in
      nursing home residents].
AB  - BACKGROUND: The pain medication appropriateness scale (PMASD) was developed in
      2006 in the USA to evaluate the quality and appropriateness of pain treatment in
      nursing home residents (NHR). This tool can be used to identify potential
      problems with the pharmacological treatment of pain. METHODS: We developed a
      German version (PMASD) adapted to the German setting and applied it in Germany to
      NHR with and without cognitive impairment for the first time. In agreement with
      the original instrument a test result of >67 % was considered as appropriate pain
      treatment. RESULTS: For the 560 analyzed NHR the average SPMAS score was 39+/-1,7
      (range from -67 to +100). Overall 72% of the study population did not achieve the
      defined threshold for appropriate pain management. CONCLUSIONS: An appropriate
      tool for quantitative evaluation of pain treatment was so far not available in
      Germany. The PMASD analysis showed deficits of pain management in NHR. This tool
      showed good practicability in Germany and could provide a valuable tool for pain
      treatment in clinical research and practice.

PMID- 24037256
TI  - [Teaching with pain].

PMID- 24037257
TI  - [Coping resources in a sample of chronic low back pain patients. Evaluation of
      the questionnaire for back pain].
AB  - BACKGROUND: The coping resources questionnaire for back pain (FBR) uses 12 items
      to measure the perceived helpfulness of different coping resources (CRs, social
      emotional support, practical help, knowledge, movement and relaxation, leisure
      and pleasure, spirituality and cognitive strategies). The aim of the study was to
      evaluate the instrument in a clinical patient sample assessed in a primary care
      setting. SAMPLE AND METHODS: The study was a secondary evaluation of empirical
      data from a large cohort study in general practices. The 58 participating primary
      care practices recruited patients who reported chronic back pain in the
      consultation. Besides the FBR and a pain sketch, the patients completed scales
      measuring depression, anxiety, resilience, sociodemographic factors and pain
      characteristics. To allow computing of retested parameters the FBR was sent to
      some of the original participants again after 6 months (90% response rate). We
      calculated consistency and retest reliability coefficients as well as
      correlations between the FBR subscales and depression, anxiety and resilience
      scores to account for validity. By means of a cluster analysis groups with
      different resource profiles were formed. Results. RESULTS: For the study 609
      complete FBR baseline data sets could be used for statistical analysis. The
      internal consistency scores ranged fromalpha=0.58 to alpha=0.78 and retest
      reliability scores were between rTT=0.41 and rTT=0.63. Correlation with
      depression, fear and resilience ranged from r=-0.38 to r=0.42. The cluster
      analysis resulted in four groups with relatively homogenous intragroup profiles
      (high CRs, low spirituality, medium CRs, low CRs). The four groups differed
      significantly in fear and depression (the more inefficient the resources the
      higher the difference) as well as in resilience (the more inefficient the lower
      the difference). The group with low CRs also reported permanent pain with no
      relief. The groups did not otherwise differ. CONCLUSIONS: The FBR is an economic
      instrument that is suitable for practical use e.g. in primary care practices to
      identify strengths and deficits in the CRs of chronic pain patients that can then
      be specified in face to face consultation. However, due to the rather low
      reliability, the use of subscales for profile differentiation and follow-up
      measurement in individual diagnoses is limited.

PMID- 24037258
TI  - [Patient careers in the orthopedic pain treatment. Sociological studies on pain
      behavior].
AB  - BACKGROUND: Based on case histories the following study raises the question why
      some pain patients remain permanently on the path of specialist pain treatment
      after initial treatment whereas other patients with similar pain reports do not.
      METHOD: In this study 134 qualitative interviews were conducted in order to
      research patient career paths. The study population included patients with back
      pain recruited from different orthopedic care settings and included persons with
      back pain from a general population not involved in specialized pain treatment.
      RESULTS: Patient career paths within medical care settings are effective in
      socializing and transforming the subjects. In the course of medical treatment
      patients learn their rights and obligations and subsequently acquire habits of
      typical pain behavior both in medical and domestic arrangements. Patients learn
      to formulate and preserve their interests and learn to align the different
      expectations which results in increasing identification with the career path.
      CONCLUSION: Conceptions of pain and pain behavior are formed in the course of
      patient careers while this is not necessarily a conscious or reflected process.
      As an unintended consequence it evolves into pain acting within the patient that
      integrates patients into distinct care milieus and holds them tight in the
      respective pain care. In these cases pain patients and their doctors fall so to
      say into a pain trap.

PMID- 24037259
TI  - Influence of chronic food deprivation on structure-function relationship of
      juvenile rat fast muscles.
AB  - In the present study, we analyze the influence of chronic undernutrition on
      protein expression, muscle fiber type composition, and fatigue resistance of the
      fast extensor digitorum longus (EDL) muscle of male juvenile rats (45 +/- 3 days
      of life; n = 25 and 31 rats for control and undernourished groups, respectively).
      Using 2D gel electrophoresis and mass spectrometry, we identified in
      undernourished muscles 12 proteins up-regulated (8 proteins of the electron
      transport chain and the glycolytic pathway, 2 cross-bridge proteins, chaperone
      and signaling proteins that are related to the stress response). In contrast, one
      down-regulated protein related to the fast muscle contractile system and two
      other proteins with no changes in expression were used as charge controls. By
      means of COX and alkaline ATPase histochemical techniques and low-frequency
      fatigue protocols we determined that undernourished muscles showed a larger
      proportion (15% increase) of Type IIa/IId fibers (oxidative-glycolytic) at the
      expense of Type IIb (glycolytic) fibers (15.5% decrease) and increased fatigue
      resistance (55.3%). In addition, all fiber types showed a significant reduction
      in their cross-sectional area (slow: 64.4%; intermediate: 63.9% and fast: 61.2%).
      These results indicate that undernourished EDL muscles exhibit an increased
      expression of energy metabolic and myofibrillar proteins which are associated
      with the predominance of oxidative and Type IIa/IId fibers and to a higher
      resistance to fatigue. We propose that such alterations may act as protective
      and/or adaptive mechanisms that counterbalance the effect of chronic
      undernourishment.

PMID- 24037260
TI  - Localisation of AMPK gamma subunits in cardiac and skeletal muscles.
AB  - The trimeric protein AMP-activated protein kinase (AMPK) is an important sensor
      of energetic status and cellular stress, and mutations in genes encoding two of
      the regulatory gamma subunits cause inherited disorders of either cardiac or
      skeletal muscle. AMPKgamma2 mutations cause hypertrophic cardiomyopathy with
      glycogen deposition and conduction abnormalities; mutations in AMPKgamma3 result
      in increased skeletal muscle glycogen. In order to gain further insight into the
      roles of the different gamma subunits in muscle and into possible disease
      mechanisms, we localised the gamma2 and gamma3 subunits, along with the more
      abundant gamma1 subunit, by immunofluorescence in cardiomyocytes and skeletal
      muscle fibres. The predominant cardiac gamma2 variant, gamma2-3B, gave a striated
      pattern in cardiomyocytes, aligning with the Z-disk but with punctate staining
      similar to T-tubule (L-type Ca(2+) channel) and sarcoplasmic reticulum (SERCA2)
      markers. In skeletal muscle fibres AMPKgamma3 localises to the I band, presenting
      a uniform staining that flanks the Z-disk, also coinciding with the position of
      Ca(2+) influx in these muscles. The localisation of gamma2-3B- and gamma3
      containing AMPK suggests that these trimers may have similar functions in the
      different muscles. AMPK containing gamma2-3B was detected in oxidative skeletal
      muscles which had low expression of gamma3, confirming that these two regulatory
      subunits may be co-ordinately regulated in response to metabolic requirements.
      Compartmentalisation of AMPK complexes is most likely dependent on the regulatory
      gamma subunit and this differential localisation may direct substrate selection
      and specify particular functional roles. 

PMID- 24037261
TI  - Gender differences following computer-navigated single- and double-bundle
      anterior cruciate ligament reconstruction.
AB  - PURPOSE: Female patients not only demonstrate an increased risk for injury, but
      also a poorer response following anterior cruciate ligament (ACL) rupture.
      However, no study has investigated gender-related differences between computer
      navigated single-bundle (SB) and double-bundle (DB) ACL reconstruction. The aim
      of this study was to evaluate the effects of gender on the outcome of computer
      navigated SB and DB ACL reconstruction and to present reference values. METHODS:
      A retrospective review of 55 consecutive patients who underwent SB (15 males, 12
      females) and DB (18 males, 10 females) ACL reconstruction with autogenous
      hamstring tendon grafts and showed a minimum follow-up of 24 months was
      conducted. Intraoperatively, the anteroposterior and rotational laxity were
      measured and the follow-up examination included pivot-shift testing, KT-1000
      arthrometer testing, International Knee Documentation Committee (IKDC) form, the
      Lysholm score and Tegner score. RESULTS: Pre-operatively, female patients showed
      a significant higher internal rotation in (p < 0.001) both the SB and DB group.
      Regarding the post-operative reduction in internal rotation, females in the SB
      group revealed a greater reduction compared to males (p < 0.001), whereas females
      in the DB group revealed a significantly greater post-operative reduction in
      anterior-posterior translation (p = 0.04). Female patients following DB ACL
      reconstruction presented a significant worse IKDC score, Lysholm score and Tegner
      score compared to male patients. All score values of the female DB group were
      worse than in the female SB group. In contrast, male patients showed better
      results of all examined clinical scores following DB procedure compared to SB
      technique. CONCLUSION: Female patients who underwent computer-navigated DB ACL
      reconstruction exhibited significantly worse outcome scores than males who
      underwent DB ACL reconstruction. The gender-based relationship between joint
      function and outcome after ACL reconstruction remains unclear and requires
      further investigation. LEVEL OF EVIDENCE: Retrospective case-control series,
      Level III.

PMID- 24037262
TI  - Postural stability in patients with anterior cruciate ligament tears with and
      without medial meniscus tears.
AB  - PURPOSE: To compare postural stability in patients with isolated anterior
      cruciate ligament (ACL) tears and ACL tears with associated meniscal tears.
      METHODS: Quadriceps and hamstring muscle strength and their ratio, as well as the
      relationships of these parameters with postural stability, were compared in 23
      patients with isolated ACL tears and 27 with combined ACL and medial meniscus
      tears. Postural stability was determined from the anterior-posterior, medial
      lateral, and overall stability indices using the Biodex Stability System.
      RESULTS: On both the involved and uninvolved sides, there were no differences in
      mean stability indices, including anterior-posterior, medial-lateral, and overall
      stability indices, in patients with isolated and combined ACL tears. In patients
      with isolated ACL tears, both overall (2.3 +/- 1.2 vs. 1.8 +/- 1.4, p = 0.033)
      and medial-lateral (1.2 +/- 0.6 vs. 1.0 +/- 0.5, p = 0.031) stability indices
      were significantly higher on the involved compared to the uninvolved side. These
      differences, however, were not observed in the combined ACL tear group.
      CONCLUSION: No significant differences in postural instability on the affected
      and unaffected sides were observed in patients with isolated ACL tears and those
      with combined ACL and medial meniscus tears. These findings indicate that there
      is no need to reduce the goal of restoring proprioception in patients with
      combined compared with isolated ACL tears. LEVEL OF EVIDENCE: III.

PMID- 24037263
TI  - Kinetochore function and chromosome segregation rely on critical residues in
      histones H3 and H4 in budding yeast.
AB  - Accurate chromosome segregation requires that sister kinetochores biorient and
      attach to microtubules from opposite poles. Kinetochore biorientation relies on
      the underlying centromeric chromatin, which provides a platform to assemble the
      kinetochore and to recruit the regulatory factors that ensure the high fidelity
      of this process. To identify the centromeric chromatin determinants that
      contribute to chromosome segregation, we performed two complementary unbiased
      genetic screens using a library of budding yeast mutants in every residue of
      histone H3 and H4. In one screen, we identified mutants that lead to increased
      loss of a nonessential chromosome. In the second screen, we isolated mutants
      whose viability depends on a key regulator of biorientation, the Aurora B protein
      kinase. Nine mutants were common to both screens and exhibited kinetochore
      biorientation defects. Four of the mutants map near the unstructured nucleosome
      entry site, and their genetic interaction with reduced IPL1 can be suppressed by
      increasing the dosage of SGO1, a key regulator of biorientation. In addition, the
      composition of purified kinetochores was altered in six of the mutants. Together,
      this work identifies previously unknown histone residues involved in chromosome
      segregation and lays the foundation for future studies on the role of the
      underlying chromatin structure in chromosome segregation. 

PMID- 24037264
TI  - High-resolution mapping of complex traits with a four-parent advanced intercross
      yeast population.
AB  - A large fraction of human complex trait heritability is due to a high number of
      variants with small marginal effects and their interactions with genotype and
      environment. Such alleles are more easily studied in model organisms, where
      environment, genetic makeup, and allele frequencies can be controlled. Here, we
      examine the effect of natural genetic variation on heritable traits in a very
      large pool of baker's yeast from a multiparent 12th generation intercross. We
      selected four representative founder strains to produce the Saccharomyces Genome
      Resequencing Project (SGRP)-4X mapping population and sequenced 192 segregants to
      generate an accurate genetic map. Using these individuals, we mapped 25 loci
      linked to growth traits under heat stress, arsenite, and paraquat, the majority
      of which were best explained by a diverging phenotype caused by a single allele
      in one condition. By sequencing pooled DNA from millions of segregants grown
      under heat stress, we further identified 34 and 39 regions selected in haploid
      and diploid pools, respectively, with most of the selection against a single
      allele. While the most parsimonious model for the majority of loci mapped using
      either approach was the effect of an allele private to one founder, we could
      validate examples of pleiotropic effects and complex allelic series at a locus.
      SGRP-4X is a deeply characterized resource that provides a framework for powerful
      and high-resolution genetic analysis of yeast phenotypes and serves as a test bed
      for testing avenues to attack human complex traits. 

PMID- 24037265
TI  - Neurodegeneration caused by polyglutamine expansion is regulated by P
      glycoprotein in Drosophila melanogaster.
AB  - Trinucleotide CAG repeat disorders are caused by expansion of polyglutamine
      (polyQ) domains in certain proteins leading to fatal neurodegenerative disorders
      and are characterized by accumulation of inclusion bodies in the neurons.
      Clearance of these inclusion bodies holds the key to improve the disease
      phenotypes, which affects basic cellular processes such as transcription, protein
      degradation and cell signaling. In the present study, we show that P-glycoprotein
      (P-gp), originally identified as a causative agent of multidrug-resistant cancer
      cells, plays an important role in ameliorating the disease phenotype. Using a
      Drosophila transgenic strain that expresses a stretch of 127 glutamine repeats,
      we demonstrate that enhancing P-gp levels reduces eye degeneration caused by
      expression of polyQ, whereas reducing it increases the severity of the disease.
      Increase in polyQ inclusion bodies represses the expression of mdr genes,
      suggesting a functional link between P-gp and polyQ. P-gp up-regulation restores
      the defects in the actin organization and precise array of the neuronal
      connections caused by inclusion bodies. beta-Catenin homolog, Armadillo, also
      interacts with P-gp and regulates the accumulation of inclusion bodies. These
      results thus show that P-gp and polyQ interact with each other, and changing P-gp
      levels can directly affect neurodegeneration. 

PMID- 24037266
TI  - Genetic studies of spectrin in the larval fat body of Drosophila melanogaster:
      evidence for a novel lipid uptake apparatus.
AB  - Spectrin cytoskeleton defects produce a host of phenotypes affecting the plasma
      membrane, cell polarity, and secretory membrane traffic. However, many of the
      underlying molecular mechanisms remain unexplained by prevailing models. Here we
      used the larval fat body of Drosophila melanogaster as a genetic model system to
      further elucidate mechanisms of alphabeta-spectrin function. The results provide
      unexpected new insights into spectrin function as well as mechanisms of dietary
      fat uptake and storage. We show that loss of alpha- or beta-spectrin in the fat
      body eliminated a population of small cortical lipid droplets and altered plasma
      membrane architecture, but did not affect viability of the organism. We present a
      novel model in which alphabeta-spectrin directly couples lipid uptake at the
      plasma membrane to lipid droplet growth in the cytoplasm. In contrast, strong
      overexpression of beta-spectrin caused fat body atrophy and larval lethality.
      Overexpression of beta-spectrin also perturbed transport of dietary fat from the
      midgut to the fat body. This hypermorphic phenotype appears to be the result of
      blocking secretion of the lipid carrier lipophorin from fat cells. However, this
      midgut phenotype was never seen with spectrin loss of function, suggesting that
      spectrin is not normally required for lipophorin secretion or function. The beta
      spectrin hypermorphic phenotype was ameliorated by co-overexpression of alpha
      spectrin. Based on the overexpression results here, we propose that beta-spectrin
      family members may be prone to hypermorphic effects (including effects on
      secretion) if their activity is not properly regulated. 

PMID- 24037267
TI  - Early colony establishment in Neurospora crassa requires a MAP kinase regulatory
      network.
AB  - Vegetative fusion is essential for the development of an interconnected colony in
      many filamentous fungi. In the ascomycete fungus Neurospora crassa, vegetative
      fusion occurs between germinated conidia (germlings) via specialized structures
      termed "conidial anastomosis tubes" (CATs) and between hyphae within a mature
      colony. In N. crassa, both CAT and hyphal fusion are under the regulation of a
      conserved MAP kinase cascade (NRC1, MEK2, and MAK2). Here we show that the
      predicted downstream target of the MAK2 kinase pathway, a Ste12-like
      transcription factor known as PP1, regulates elements required for CAT and hyphal
      fusion. The PP1 regulatory network was revealed by expression profiling of wild
      type and the Deltapp-1 mutant during conidial germination and colony
      establishment. To identify targets required for cell fusion more specifically,
      expression-profiling differences were assessed via inhibition of MAK2 kinase
      activity during chemotropic interactions and cell fusion. These approaches led to
      the identification of new targets of the cell fusion pathway that, when mutated,
      showed alterations in chemotropic signaling and cell fusion. In particular,
      conidial germlings carrying a deletion of NCU04732 (Deltaham-11) failed to show
      chemotropic interactions and cell fusion. However, signaling (as shown by
      oscillation of MAK2 and SO to CAT tips), chemotropism, and cell fusion were
      restored in Deltaham-11 germlings when matched with wild-type partner germlings.
      These data reveal novel insights into the complex process of self-signaling,
      germling fusion, and colony establishment in filamentous fungi. 

PMID- 24037268
TI  - Relating phylogenetic trees to transmission trees of infectious disease
      outbreaks.
AB  - Transmission events are the fundamental building blocks of the dynamics of any
      infectious disease. Much about the epidemiology of a disease can be learned when
      these individual transmission events are known or can be estimated. Such
      estimations are difficult and generally feasible only when detailed
      epidemiological data are available. The genealogy estimated from genetic
      sequences of sampled pathogens is another rich source of information on
      transmission history. Optimal inference of transmission events calls for the
      combination of genetic data and epidemiological data into one joint analysis. A
      key difficulty is that the transmission tree, which describes the transmission
      events between infected hosts, differs from the phylogenetic tree, which
      describes the ancestral relationships between pathogens sampled from these hosts.
      The trees differ both in timing of the internal nodes and in topology. These
      differences become more pronounced when a higher fraction of infected hosts is
      sampled. We show how the phylogenetic tree of sampled pathogens is related to the
      transmission tree of an outbreak of an infectious disease, by the within-host
      dynamics of pathogens. We provide a statistical framework to infer key
      epidemiological and mutational parameters by simultaneously estimating the
      phylogenetic tree and the transmission tree. We test the approach using
      simulations and illustrate its use on an outbreak of foot-and-mouth disease. The
      approach unifies existing methods in the emerging field of phylodynamics with
      transmission tree reconstruction methods that are used in infectious disease
      epidemiology. 

PMID- 24037271
TI  - Development of mediator-type biosensor to wirelessly monitor whole cholesterol
      concentration in fish.
AB  - We developed a wireless monitoring system to monitor fish condition by tracking
      the change in whole cholesterol concentration. The whole cholesterol
      concentration of fish is a source of steroid hormones or indicator of immunity
      level, which makes its detection important for tracking physiological condition
      of fish. Wireless monitoring system comprises of mediator-type biosensor and
      wireless transmission device. Biosensor is implantable to fish body, and
      transmission device is so light, in that fish is allowed to swim freely during
      monitoring. Cholesterol esterase and oxidase were fixated on to the detection
      site of biosensor and used to detect the whole cholesterol concentration.
      However, cholesterol oxidase incorporates oxidation-reduction reaction of oxygen
      for detection, which concentration fluctuates easily due to change in
      environmental condition. Meanwhile, mediator-type biosensor enables monitoring of
      whole cholesterol concentration by using mediator to substitute that oxidation
      reduction reaction of oxygen. Characteristic of fabricated mediator-type
      biosensor was tested. The sensor output current of mediator-type biosensor
      remained stable compared to output current of non-mediator-type biosensor under
      fluctuating oxygen concentration of 0-8 ppm, which implied that this sensor is
      less affected by change in dissolved oxygen concentration. That biosensor was
      then implanted into fish for wireless monitoring. As a result, approximately 48 h
      of real-time monitoring was successful.

PMID- 24037270
TI  - A locus in Drosophila sechellia affecting tolerance of a host plant toxin.
AB  - Many insects feed on only one or a few types of host. These host specialists
      often evolve a preference for chemical cues emanating from their host and develop
      mechanisms for circumventing their host's defenses. Adaptations like these are
      central to evolutionary biology, yet our understanding of their genetics remains
      incomplete. Drosophila sechellia, an emerging model for the genetics of host
      specialization, is an island endemic that has adapted to chemical toxins present
      in the fruit of its host plant, Morinda citrifolia. Its sibling species, D.
      simulans, and many other Drosophila species do not tolerate these toxins and
      avoid the fruit. Earlier work found a region with a strong effect on tolerance to
      the major toxin, octanoic acid, on chromosome arm 3R. Using a novel assay, we
      narrowed this region to a small span near the centromere containing 18 genes,
      including three odorant binding proteins. It has been hypothesized that the
      evolution of host specialization is facilitated by genetic linkage between
      alleles contributing to host preference and alleles contributing to host usage,
      such as tolerance to secondary compounds. We tested this hypothesis by measuring
      the effect of this tolerance locus on host preference behavior. Our data were
      inconsistent with the linkage hypothesis, as flies bearing this tolerance region
      showed no increase in preference for media containing M. citrifolia toxins, which
      D. sechellia prefers. Thus, in contrast to some models for host preference,
      preference and tolerance are not tightly linked at this locus nor is increased
      tolerance per se sufficient to change preference. Our data are consistent with
      the previously proposed model that the evolution of D. sechellia as a M.
      citrifolia specialist occurred through a stepwise loss of aversion and gain of
      tolerance to M. citrifolia's toxins. 

PMID- 24037272
TI  - The effect of K(+), Ca (2+), and Mg (2+) on sperm motility in the perch, Perca
      fluviatilis.
AB  - This study investigated the effect of 0.25-5 mM K(+), Ca(2+), and Mg(2+) on sperm
      motility in the perch, Perca fluviatilis. In 75 mM NaCl, the used motility
      activating solution, motility rate, and swimming velocity decreased within the
      first 4 min after activation, and the rate of locally motile sperm increased.
      Thereafter, the motility parameters remained constant for periods >20 min. Based
      on the decrease in sperm motility, two types of semen samples could be
      distinguished. Semen samples of type I retained a high motility rate of >65 %
      after 20 min, and the rate of locally motile sperm was <20 %. In semen samples of
      type II, the motility rate decreased to values <30 % after 20 min, and the rate
      of locally motile sperm exceeded >50 %. Ca(2+) and Mg(2+) concentrations of 0.25
      0.5 mM had no effect on the sperm motility parameters 10 s after activation,
      while 0.25 mM K(+) increased the swimming velocity. K(+), Ca(2+), and Mg(2+)
      concentrations >=1.5 mM had suppressive effects on the sperm motility 10 s after
      activation. No differences were found between the two semen types. Twenty minutes
      after activation, type I semen was not affected by the tested cations. On the
      contrary, 0.25-2.5 mM K(+), 0.25 mM Mg(2+), and 0.25-2.5 mM Ca(2+) significantly
      increased the sperm motility rate and/or sperm velocity of type II semen.
      Therefore, supplementation of saline solution with cations might stabilize the
      motility of perch sperm, which can be a benefit for experimental purposes and for
      specific handling procedures in aquaculture.

PMID- 24037273
TI  - Inactivation kinetics of formaldehyde on N-acetyl-beta-D-glucosaminidase from
      Nile tilapia (Oreochromis niloticus).
AB  - Formaldehyde is a widely used sanitizer in aquaculture in China, while the
      appropriate concentration is not available to be used effectively and without
      damage to tilapia much less to its reproductive function. N-acetyl-beta-D
      glucosaminidase (EC 3.2.1.52, NAGase), hydrolyzing the oligomers of N-acetyl-beta
      D-glucosamine into monomer, is proved to be correlated with reproduction of male
      animals. In this paper, NAGase from spermary of tilapia was chosen as the
      material to study the effects of formaldehyde on its activity in order to further
      investigate the effects of formaldehyde use on tilapia reproduction. The results
      showed the relationship between the residual enzyme activity and the
      concentration of formaldehyde was concentration dependent, and the IC50 value was
      estimated to be 3.2 +/- 0.1 %. Appropriate concentration of formaldehyde leaded
      to competitive reversible inhibition on tilapia NAGase. Moreover, formaldehyde
      could reduce the thermal and pH stability of the enzyme. The inactivation
      kinetics of formaldehyde on the enzyme was studied using the kinetic method of
      substrate reaction. The inactivation model was setup, and the rate constants were
      determined. The results showed that the inactivation of formaldehyde on tilapia
      NAGase was a slow, reversible reaction with partially residual activity. The
      results will give some basis to determine the concentration of formaldehyde used
      in tilapia culture.

PMID- 24037274
TI  - Structural and theoretical studies of intermolecular dihydrogen bonding in
      [(C6F5)2(C6Cl5)B]-H...H-[TMP].
AB  - The product of the intermolecular 'frustrated Lewis pair' (FLP)
      B(C6F5)2(C6Cl5)/2,2,6,6-tetramethylpiperidine and H2 has been studied by single
      crystal neutron diffraction. This is the first structurally characterised example
      of a geometrically unconstrained dihydrogen (H...H) bond within a hydrogenated
      FLP system.

PMID- 24037275
TI  - Warfarin modulates the nitrite reductase activity of ferrous human serum heme
      albumin.
AB  - Human serum heme-albumin (HSA-heme-Fe) displays reactivity and spectroscopic
      properties similar to those of heme proteins. Here, the nitrite reductase
      activity of ferrous HSA-heme-Fe [HSA-heme-Fe(II)] is reported. The value of the
      second-order rate constant for the reduction of [Formula: see text] to NO and the
      concomitant formation of nitrosylated HSA-heme-Fe(II) (i.e., k on) is 1.3 M(-1)
      s(-1) at pH 7.4 and 20  degrees C. Values of k on increase by about one order of
      magnitude for each pH unit decrease between pH 6.5 to 8.2, indicating that the
      reaction requires one proton. Warfarin inhibits the HSA-heme-Fe(II) reductase
      activity, highlighting the allosteric linkage between the heme binding site [also
      named the fatty acid (FA) binding site 1; FA1] and the drug-binding cleft FA2.
      The dissociation equilibrium constant for warfarin binding to HSA-heme-Fe(II) is
      (3.1 +/- 0.4) * 10(-4) M at pH 7.4 and 20  degrees C. These results: (1)
      represent the first evidence for the [Formula: see text] reductase activity of
      HSA-heme-Fe(II), (2) highlight the role of drugs (e.g., warfarin) in modulating
      HSA(-heme-Fe) functions, and (3) strongly support the view that HSA acts not only
      as a heme carrier but also displays transient heme-based reactivity. 

PMID- 24037276
TI  - Determinants of high cardiovascular risk in relation to plaque-composition of a
      non-culprit coronary segment visualized by near-infrared spectroscopy in patients
      undergoing percutaneous coronary intervention.
AB  - AIM: The aim of this study was to determine the relationship between clinical and
      blood characteristics of a vascular inflammatory milieu and coronary plaque
      composition visualized by near-infrared spectroscopy (NIRS) in percutaneous
      coronary intervention (PCI) patients. METHODS AND RESULTS: Between April 2009 and
      January 2011, we performed NIRS in 208 patients who underwent PCI or invasive
      diagnostic coronary exploration for various indications. Imaging was performed of
      one non-intervened coronary segment after the initial procedure. Univariate and
      multivariate linear regression analyses were applied to evaluate the relationship
      between the acquired NIRS-derived lipid core burden index (LCBI) and clinical and
      blood (lipids and hs-C-reactive protein) characteristics. Patients with a history
      of hypercholesterolaemia [median 48 (inter-quartile range 21-101) vs. 38 (13-70),
      P = 0.043] and multi-vessel disease [55 (24-104) vs. 32 (12-71), P = 0.012] had
      higher LCBI levels. Men had higher LCBI than women [48 (21-95) vs. 27 (9-59), P =
      0.003]. Hypercholesterolaemia and gender remained significant in multivariate
      regression analysis, whereas also a history of non-cardiac vascular disease and
      beta-blockers were positively associated with LCBI. Altogether 23.2% of the
      variability in LCBI could be explained by clinical and blood characteristics.
      CONCLUSION: Clinical characteristics reflecting patients with a high
      cardiovascular risk profile explained 23.2% of the variability in LCBI, whereas
      blood biomarkers added little. Further research is warranted to evaluate whether
      NIRS has the potential to provide additional prognostic information about
      patients' cardiovascular risk.

PMID- 24037277
TI  - The expression of calcitonin gene-related Peptide and acetylcholine in the
      vestibular-related nucleus population of wild-type mice and retinal degeneration
      fast mice after rotary stimulation.
AB  - Due to the lack of an appropriate animal model, few studies have addressed the
      integration of visual and vestibular information in the visual system. Using a
      mouse model with a visual defect (retinal degeneration fast, rdf), we have
      verified that the prepositus hypoglossal nucleus (PrH) and the Kooy cap of the
      inferior olive medial nucleus (IOK) are key regions in which visual and
      vestibular information integrate. Although the integration regions were
      identified, the precise mechanisms of integration require further investigation.
      The rdf mice and wild-type Kunming mice were randomly assigned to experimental
      and control subgroups, respectively. Mice in the experimental groups were exposed
      to rotary motion for 30 min three times at 24-h intervals, whereas mice in the
      control groups were not exposed to rotary motion. Differences in the number of
      calcitonin gene-related peptide positive (CGRP-positive) and choline
      acetyltransferase positive (ChAT-positive) neurons in the vestibular-related
      nucleus populations of two types of mice were determined. After rotatory
      stimulus, the number of CGRP-positive and ChAT-positive neurons in the PrH and
      the IOK was significantly less in rdf mice compared with that in wild-type mice.
      There were differences in the number of CGRP-positive and ChAT-positive neurons
      in the other vestibular-related regions, but the differences were not
      significant, except the difference in the number of ChAT-positive neurons in the
      medial vestibular nucleus. The expression patterns of CGRP and ChAT were similar
      to that of Fos in the vestibular-related regions in the two types of mice after
      rotatory stimulus. The number of CGRP-positive and ChAT-positive neurons and the
      number of active nerve cells were consistent in those regions in the two types of
      mice after rotary stimulus. Therefore, we speculated that CGRP and Ach generated
      and released by neurons in the PrH and the IOK may play roles in the sensory
      integration of visual and vestibular information in mice.

PMID- 24037279
TI  - Cost-effective CO2 capture based on in silico screening of zeolites and process
      optimization.
AB  - A hierarchical computational approach is introduced that combines materials
      screening with process optimization. This approach leads to novel materials for
      cost-effective CO2 capture. Zeolites are screened using shape, size, and
      adsorption selectivities. Next, process optimization is introduced to generate a
      rank-ordered list based on total cost of capture and compression. We not only
      select the most cost-effective materials, but we also attain the optimal process
      conditions while satisfying purity, recovery, and other process constraints. The
      top ten zeolites (AHT, NAB, MVY, ABW, AWO, WEI, VNI, TON, OFF and ITW) can
      capture and compress CO2 to 150 bar from a mixture of 14% CO2 and 86% N2 at less
      than $30 per ton of CO2 captured. Several zeolites have moderate selectivities,
      yet they cost-effectively capture CO2 with 90% purity and 90% recovery using a 4
      step adsorption process. Such nonintuitive selection demonstrates the necessity
      of combining materials-centric and process-centric viewpoints. 

PMID- 24037269
TI  - Genomic resources for gene discovery, functional genome annotation, and
      evolutionary studies of maize and its close relatives.
AB  - Maize is one of the most important food crops and a key model for genetics and
      developmental biology. A genetically anchored and high-quality draft genome
      sequence of maize inbred B73 has been obtained to serve as a reference sequence.
      To facilitate evolutionary studies in maize and its close relatives, much like
      the Oryza Map Alignment Project (OMAP) (www.OMAP.org) bacterial artificial
      chromosome (BAC) resource did for the rice community, we constructed BAC
      libraries for maize inbred lines Zheng58, Chang7-2, and Mo17 and maize wild
      relatives Zea mays ssp. parviglumis and Tripsacum dactyloides. Furthermore, to
      extend functional genomic studies to maize and sorghum, we also constructed
      binary BAC (BIBAC) libraries for the maize inbred B73 and the sorghum landrace
      Nengsi-1. The BAC/BIBAC vectors facilitate transfer of large intact DNA inserts
      from BAC clones to the BIBAC vector and functional complementation of large DNA
      fragments. These seven Zea Map Alignment Project (ZMAP) BAC/BIBAC libraries have
      average insert sizes ranging from 92 to 148 kb, organellar DNA from 0.17 to 2.3%,
      empty vector rates between 0.35 and 5.56%, and genome equivalents of 4.7- to 8.4
      fold. The usefulness of the Parviglumis and Tripsacum BAC libraries was
      demonstrated by mapping clones to the reference genome. Novel genes and alleles
      present in these ZMAP libraries can now be used for functional complementation
      studies and positional or homology-based cloning of genes for translational
      genomics. 

PMID- 24037278
TI  - The geographic distribution of obesity by census tract among 59 767 insured
      adults in King County, WA.
AB  - OBJECTIVE: To evaluate the geographic concentration of adult obesity prevalence
      by census tract (CT) in King County, WA, in relation to social and economic
      factors. METHODS AND DESIGN: Measured heights and weights from 59 767 adult men
      and women enrolled in the Group Health (GH) healthcare system were used to
      estimate obesity prevalence at the CT level. CT-level measures of socioeconomic
      status (SES) were median home values of owner-occupied housing units, percent of
      residents with a college degree and median household incomes, all drawn from the
      2000 Census. Spatial regression models were used to assess the relation between
      CT-level obesity prevalence and socioeconomic variables. RESULTS: Smoothed CT
      obesity prevalence, obtained using an Empirical Bayes tool, ranged from 16.2
      43.7% (a 2.7-fold difference). The spatial pattern of obesity was non-random,
      showing a concentration in south and southeast King County. In spatial regression
      models, CT-level home values and college education were more strongly associated
      with obesity than household incomes. For each additional $100 000 in median home
      values, CT obesity prevalence was 2.3% lower. The three SES factors together
      explained 70% of the variance in CT obesity prevalence after accounting for
      population density, race/ethnicity, age and spatial dependence. CONCLUSIONS: To
      our knowledge, this is the first report to show major social disparities in adult
      obesity prevalence at the CT scale that is based, moreover, on measured heights
      and weights. Analyses of data at sufficiently fine geographic scale are needed to
      guide targeted local interventions to stem the obesity epidemic.

PMID- 24037280
TI  - A computational approach to mechanistic and predictive toxicology of pesticides.
AB  - Emerging challenges of managing and interpreting large amounts of complex
      biological data have given rise to the growing field of computational biology. We
      investigated the applicability of an integrated systems toxicology approach on
      five selected pesticides to get an overview of their modes of action in humans,
      to group them according to their modes of action, and to hypothesize on their
      potential effects on human health. We extracted human proteins associated to
      prochloraz, tebuconazole, epoxiconazole, procymidone, and mancozeb and enriched
      each protein set by using a high confidence human protein interactome. Then, we
      explored modes of action of the chemicals, by integrating protein-disease
      information to the resulting protein networks. The dominating human adverse
      effects affected were reproductive disorders followed by adrenal diseases. Our
      results indicated that prochloraz, tebuconazole, and procymidone exerted their
      effects mainly via interference with steroidogenesis and nuclear receptors.
      Prochloraz was associated to a large number of human diseases, and together with
      tebuconazole showed several significant associations to Testicular Dysgenesis
      Syndrome. Mancozeb showed a differential mode of action, involving inflammatory
      processes. This method provides an efficient way of overviewing data and grouping
      chemicals according to their mode of action and potential human adverse effects.
      Such information is valuable when dealing with predictions of mixture effects of
      chemicals and may contribute to the development of adverse outcome pathways. 

PMID- 24037281
TI  - Effects of wall distensibility in hemodynamic simulations of an arteriovenous
      fistula.
AB  - Arteriovenous fistulae are created surgically to provide adequate access for
      dialysis patients suffering from end-stage renal disease. It has long been
      hypothesized that the rapid blood vessel remodeling occurring after fistula
      creation is in part a process to restore the mechanical stresses to some
      preferred level, i.e., mechanical homeostasis. The current study presents fluid
      structure interaction (FSI) simulations of a patient-specific model of a mature
      arteriovenous fistula reconstructed from 3D ultrasound scans. The FSI results are
      compared with previously published data of the same model but with rigid walls.
      Ultrasound-derived wall motion measurements are also used to validate the FSI
      simulations of the wall motion. Very large time-averaged shear stresses, 10-15
      Pa, are calculated at the fistula anastomosis in the FSI simulations, values
      which are much larger than what is typically thought to be the normal homeostatic
      shear stress in the peripheral vasculature. Although this result is
      systematically lower by as much as 50% compared to the analogous rigid-walled
      simulations, the inclusion of distensible vessel walls in hemodynamic simulations
      does not reduce the high anastomotic shear stresses to "normal" values.
      Therefore, rigid-walled analyses may be acceptable for identifying high shear
      regions of arteriovenous fistulae.

PMID- 24037282
TI  - Acute kidney injury caused by Crotalus and Bothrops snake venom: a review of
      epidemiology, clinical manifestations and treatment.
AB  - Ophidic accidents are an important public health problem due to their incidence,
      morbidity and mortality. An increasing number of cases have been registered in
      Brazil in the last few years. Several studies point to the importance of knowing
      the clinical complications and adequate approach in these accidents. However,
      knowledge about the risk factors is not enough and there are an increasing number
      of deaths due to these accidents in Brazil. In this context, acute kidney injury
      (AKI) appears as one of the main causes of death and consequences for these
      victims, which are mainly young males working in rural areas. Snakes of the
      Bothrops and Crotalus genera are the main responsible for renal involvement in
      ophidic accidents in South America. The present study is a literature review of
      AKI caused by Bothrops and Crotalus snake venom regarding diverse
      characteristics, emphasizing the most appropriate therapeutic approach for these
      cases. Recent studies have been carried out searching for complementary therapies
      for the treatment of ophidic accidents, including the use of lipoic acid,
      simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and
      Rubiaceae seem to have a beneficial role in the treatment of this type of
      envenomation. Future studies will certainly find new therapeutic measures for
      ophidic accidents. 

PMID- 24037283
TI  - In vitro phytotherapy of vector snails by binary combinations of larvicidal
      active components in effective control of fascioliasis.
AB  - A food-borne trematode infection fascioliasis is one among common public health
      problems worldwide. It caused a great economic loss for the human race. Control
      of snail population below a certain threshold level is one of the important
      methods in the campaign to reduce the incidence of fascioliasis. The life cycle
      of the parasite can be interrupted by killing the snail or Fasciola larva redia
      and cercaria inside of the snail Lymnaea acuminata. In vitro toxicity of
      different binary combinations (1:1 ratio) of plant-derived larvicidal active
      components such as citral, ferulic acid, umbelliferone, azadirachtin and allicin
      against Fasciola redia and cercaria were tested. The mortality of larvae was
      observed at 2h, 4h, 6h and 8h of treatment. In in vitro condition azadirachtin +
      allicin (1:1 ratio) was highly toxic against redia and cercaria (8h LC50 0.006
      and 0.005 mg/L). Toxicity of citral + ferulic acid was lowest against redia and
      cercaria larvae. 

PMID- 24037284
TI  - High prevalence of Strongyloides stercoralis infection among the elderly in
      Brazil.
AB  - Little is known about the frequency of intestinal parasites in the elderly due to
      a lack of attention given to the occurrence of these infections among older
      adults. This study compares the frequency of Strongyloides stercoralis and other
      enteroparasites between elderly living in nursing homes (n = 100) and those
      noninstitutionalized (n = 100) from Uberlandia, state of Minas Gerais,
      southeastern Brazil, associated with data of epidemiological and socio
      demographic conditions. Through coproparasitological examination of both groups,
      enteroparasites were detected in 15 of 200 individuals examined (7.5%; CI: 5.1-
      9.9). S. stercoralis was the most frequent parasite 10/200 (5%; CI: 4.2-5.8),
      being significantly higher in males and in individuals with autonomy for daily
      living activities. There were no statistical differences in the prevalence of
      parasites between the two groups compared. In conclusion, S. stercoralis
      infection was highly prevalent in elderly patients and it does not depend on
      whether the individual was institutionalized or not. 

PMID- 24037285
TI  - Prevalence of herpes simplex virus type 2 and risk factors associated with this
      infection in women in southern Brazil.
AB  - The herpes simplex virus type 2 (HVS-2) is the most prevalent infection
      worldwide. It is a cofactor in the acquisition of human immunodeficiency virus
      (HIV) and the persistence of human papillomavirus (HPV). This study evaluated the
      prevalence of HSV-2, using the polymerase chain reaction (PCR), and associated
      factors in patients treated at the Federal University of Rio Grande (FURG) and
      Basic Health Units (BHU) in Rio Grande, Brazil. The observed prevalence of HSV-2
      was 15.6%. Among the 302 women studied, 158 had received assistance in BHU and
      144 were treated at FURG. The prevalence of HSV-2 in these groups was 10.8% and
      20.8%, respectively, RR 1.9 and p = 0.012. Knowledge about the Pap smear, and the
      presence of lesions showed no association with HSV-2 infection. Multivariate
      analysis showed that the variable that most influenced the risk of HSV-2
      infection was the presence of HIV infection, with a relative risk of 1.9 and p =
      0.04. DISCUSSION: Genital ulcers are an important entry point for HIV, and condom
      use is an important strategy to reduce transmission of HIV and HSV-2.

PMID- 24037286
TI  - Establishing the reference range for T lymphocytes subpopulations in adults and
      children from Brazil.
AB  - In Brazil, the existing reference values for T-lymphocytes subsets are based on
      data originated in other countries. There is no local information on normal
      variation for these parameters in Brazilian adults and children. We evaluated the
      normal variation found in blood donors from five large Brazilian cities, in
      different regions, and in children living in Salvador, and Rio de Janeiro. All
      samples were processed by flow cytometry. The results were analyzed according to
      region, gender, and lifestyle of blood donors. A total of 641 adults (63% males),
      and 280 children (58% males) were involved in the study. The absolute CD3+, and
      CD4+ cells count were significantly higher for females (adults and children).
      Higher CD4+ cell count in adults was associated with smoking, while higher CD8+
      count was found among female children. Higher counts, for all T-cells subsets,
      were detected in blood donors from southeast / south regions while those living
      in the northern region had the lowest values. Individuals from midwestern and
      northeastern regions had an intermediate count for all these cells subsets.
      However, these differences did not reach statistical significance. In Brazil,
      gender and smoking, were the main determinants of differences in T-lymphocytes
      reference values. 

PMID- 24037287
TI  - An upward trend in DNA p16ink4a methylation pattern and high risk HPV infection
      according to the severity of the cervical lesion.
AB  - High-risk human papillomavirus (hr-HPV) infection is necessary but not sufficient
      for cervical cancer development. Recently, P16INK4A gene silencing through
      hypermethylation has been proposed as an important cofactor in cervical
      carcinogenesis due to its tumor suppressor function. We aimed to investigate
      P16INK4A methylation status in normal and neoplastic epithelia and evaluate an
      association with HPV infection and genotype. This cross-sectional study was
      performed with 141 cervical samples from patients attending Hospital Moncorvo
      Filho, Rio de Janeiro. HPV detection and genotyping were performed through PCR
      and P16INK4A methylation by nested-methylation specific PCR (MSP). HPV frequency
      was 62.4% (88/141). The most common HPV were HPV16 (37%), HPV18 (16.3%) and
      HPV33/45(15.2%). An upward trend was observed concerning P16INK4A methylation and
      lesion degree: normal epithelia (10.7%), low grade lesions (22.9%), high grade
      (57.1%) and carcinoma (93.1%) (p < 0.0001). A multivariate analysis was performed
      to evaluate an association between methylation, age, tobacco exposure, HPV
      infection and genotyping. A correlation was found concerning methylation with HPV
      infection (p < 0.0001), hr-HPV (p = 0.01), HSIL (p < 0.0007) and malignant
      lesions (p < 0.0001). Since viral infection and epigenetic alterations are
      related to cervical carcinoma, we suggest that P16INK4A methylation profile maybe
      thoroughly investigated as a biomarker to identify patients at risk of cancer. 

PMID- 24037288
TI  - Serological survey of Ehrlichia species in dogs, horses and humans: zoonotic
      scenery in a rural settlement from southern Brazil.
AB  - The aims of this study were to determine the seroprevalence of Ehrlichia spp. and
      risk factors for exposure in a restricted population of dogs, horses, and humans
      highly exposed to tick bites in a Brazilian rural settlement using a commercial
      ELISA rapid test and two indirect immunofluorescent assays (IFA) with E. canis
      and E. chaffeensis crude antigens. Serum samples from 132 dogs, 16 horses and 100
      humans were used. Fifty-six out of 132 (42.4%) dogs were seropositive for E.
      canis. Dogs > one year were more likely to be seropositive for E. canis than dogs
      <= one year (p = 0.0051). Ten/16 (62.5%) and 8/16 (50%) horses were seropositive
      by the commercial ELISA and IFA, respectively. Five out of 100 (5%) humans were
      seropositive for E. canis and E. chaffeensis. Rhipicephalus sanguineus (n = 291,
      97.98%) on dogs and Amblyomma cajennense (n = 25, 96.15%) on horses were the most
      common ticks found. In conclusion, anti-Ehrlichia spp. antibodies were found in
      horses; however, the lack of a molecular characterization precludes any
      conclusion regarding the agent involved. Additionally, the higher seroprevalence
      of E. canis in dogs and the evidence of anti-Ehrlichia spp. antibodies in humans
      suggest that human cases of ehrlichiosis in Brazil might be caused by E. canis,
      or other closely related species. 

PMID- 24037289
TI  - Hypoxic stress, hepatocytes and CACO-2 viability and susceptibility to Shigella
      flexneri invasion.
AB  - Inflammation due to Shigella flexneri can cause damage to the colonic mucosa and
      cell death by necrosis and apoptosis. This bacteria can reach the bloodstream in
      this way, and the liver through portal veins. Hypoxia is a condition present in
      many human diseases, and it may induce bacterial translocation from intestinal
      lumen. We studied the ability of S. flexneri to invade rat hepatocytes and Caco-2
      cells both in normoxic and hypoxic microenvironments, as well as morphological
      and physiological alterations in these cells after infection under hypoxia. We
      used the primary culture of rat hepatocytes as a model of study. We analyzed the
      following parameters in normoxic and hypoxic conditions: morphology, cell
      viability, bacterial recovery and lactate dehydrogenase (LDH) released. The
      results showed that there were fewer bacteria within the Caco-2 cells than in
      hepatocytes in normoxic and hypoxic conditions. We observed that the higher the
      multiplicity of infection (MOI) the greater the bacterial recovery in
      hepatocytes. The hypoxic condition decreased the bacterial recovery in
      hepatocytes. The cytotoxicity evaluated by LDH released by cells was
      significantly higher in cells submitted to hypoxia than normoxia. Caco-2 cells in
      normoxia released 63% more LDH than hepatocytes. LDH increased 164% when
      hepatocytes were submitted to hypoxia and just 21% when Caco-2 cells were in the
      same condition. The apoptosis evaluated by Tunel was significantly higher in
      cells submitted to hypoxia than normoxia. When comparing hypoxic cells, we
      obtained more apoptotic hepatocytes than apoptotic Caco-2 cells. Concluding our
      results contribute to a better knowledge of interactions between studied cells
      and Shigella flexneri. These data may be useful in the future to define
      strategies to combat this virulent pathogen. 

PMID- 24037290
TI  - Epidemiological profile of snakebite accidents in a metropolitan area of
      northeast Brazil.
AB  - The aim of this study was to describe the epidemiological profile of snakebite
      accidents reported by the toxicological assistance center in Fortaleza, Ceara,
      Brazil. Database information on snakebite accidents was analyzed regarding the
      period from January 2003 to December 2011. A total of 1063 cases were found. The
      accidents occurred during the rainy months (March, April and May), in urban areas
      (52.3%), affecting individuals younger than 50 years and predominantly among
      males (70.7%). The lower limbs were the most frequently affected body area
      (33.7%). Most accidents involved non-venomous snakes (76.1%). The genus Bothrops
      was the main one involved in venomous accidents (83%). It is expected that this
      study can be used as the substrate to improve healthcare surveillance and
      implementing better measures for the treatment of this population. 

PMID- 24037291
TI  - Application of 6-nitrocoumarin as a substrate for the fluorescent detection of
      nitroreductase activity in Sporothrix schenckii.
AB  - INTRODUCTION: Sporothrix schenckii is a thermal dimorphic pathogenic fungus
      causing a subcutaneous mycosis, sporotrichosis. Nitrocoumarin represents a
      fluorogenic substrate class where the microbial nitroreductase activity produces
      several derivatives, already used in several other enzyme assays. The objective
      of this study was the analysis of 6-nitrocoumarin (6-NC) as a substrate to study
      the nitroreductase activity in Sporothrix schenckii. METHODS: Thirty-five samples
      of S. schenckii were cultivated for seven, 14 and 21 days at 35  degrees C in a
      microculture containing 6-nitrocoumarin or 6-aminocoumarin (6-AC) dissolved in
      dimethyl sulfoxide or dimethyl sulfoxide as a negative control, for posterior
      examination under an epifluorescence microscope. The organic layer of the seven,
      14 and 21-day cultures was analyzed by means of direct illumination with 365 nm
      UV light and by means of elution on G silica gel plate with hexane:ethyl acetate
      1:4 unveiled with UV light. RESULTS: All of the strains showed the presence of 6
      AC (yellow fluorescence) and 6-hydroxylaminocoumarin (blue fluorescence) in thin
      layer chromatography, which explains the green fluorescence observed in the
      fungus structure. CONCLUSION: The nitroreductase activity is widely distributed
      in the S. schenckii complex and 6-NC is a fluorogenic substrate of easy access
      and applicability for the nitroreductase activity detection.

PMID- 24037292
TI  - Body weight as a determinant of clinical evolution in hamsters (Mesocricetus
      auratus) infected with Leishmania (Viannia) panamensis.
AB  - The clinical outcome of infection with Leishmania species of the subgenus Viannia
      in hamster model (Mesocricetus auratus) has shown to be different depending on
      experimental protocol. Body weight has been a relevant determinant of the
      clinical outcome of the infection in hamsters with visceral leishmaniasis but its
      importance as a clinical parameter in hamsters with cutaneous leishmaniasis is
      not known. In this study, the clinical evolution of infection with L. (V)
      panamensis was evaluated in juvenile and adult male hamsters during 11 weeks by
      comparing clinical parameters such as attitude, temperature, respiratory rate,
      appearance of the stool, and body weight between infected and non-infected
      groups. Results showed that body weight decreased in adult hamsters after
      infection by L. (V) panamensis; this observation supports the use of body weight
      as an additional parameter to define the management or treatment of cutaneous
      leishmaniasis in infected adult hamsters used as an animal experimental model for
      leishmaniasis. 

PMID- 24037293
TI  - Protective effect of the probiotic Saccharomyces boulardii in Toxocara canis
      infection is not due to direct action on the larvae.
AB  - In a previous study our group found that the probiotic Saccharomyces boulardii
      was capable of reducing the intensity of infection in mice with toxocariasis. In
      order to assess whether the mechanism involved would be a direct action of the
      probiotic on Toxocara canis larvae, this study was designed. Both probiotics were
      singly cultivated in plates containing RPMI 1640 medium and T. canis larvae. S.
      boulardii and B. cereus var. toyoi cultures presented 97.6% and 95.7% of larvae
      with positive motility, respectively, and absence of color by the dye trypan
      blue, not representing significant difference to the control group (p > 0.05). We
      conclude that none of the probiotics showed in vitro effects on T. canis larvae
      and that the interaction with the intestinal mucosa is necessary for the
      development of the protective effect of S. boulardii. 

PMID- 24037294
TI  - Males, ages >= 45 years, businessperson, floating population, and rural residents
      may be considered high-risk groups for tuberculosis infection in Guangzhou,
      China: a review of 136,394 tb confirmed cases.

PMID- 24037295
TI  - Prevalence of intestinal parasitism and associated symptomatology among
      hemodialysis patients.

PMID- 24037296
TI  - Biodegradability of a polyacrylate superabsorbent in agricultural soil.
AB  - Superabsorbent polymers (SAP) are used, inter alia, as soil amendment to increase
      the water holding capacity of soils. Biodegradability of soil conditioners has
      become a desired key characteristic to protect soil and groundwater resources.
      The present study characterized the biodegradability of one acrylate based SAP in
      four agricultural soils and at three temperatures. Mineralisation was measured as
      the (13)CO2 efflux from (13)C-labelled SAP in soil incubations. The SAP was
      either single-labelled in the carboxyl C-atom or triple-labelled including
      additionally the two C-atoms interlinked in the SAP backbone. The dual labelling
      allowed estimating the degradation of the polyacrylate main chain. The (13)CO2
      efflux from samples was measured using an automated system including wavelength
      scanned cavity ring-down spectroscopy. Based on single-labelled SAP, the mean
      degradation after 24 weeks varied between 0.45% in loamy sand and 0.82% in loam.
      However, the differences between degradation rates in different soils were not
      significant due to a large intra-replicate variability. Similarly, mean
      degradation did not differ significantly between effective temperature regimes of
      20 degrees  and 30  degrees C after 12 weeks. Results from the triple-labelled
      SAP were lower as compared to their single-labelled variant. Detailed results
      suggest that the polyacrylate main chain degraded in the soils, if at all, at
      rates of 0.12-0.24 % per 6 months.

PMID- 24037297
TI  - Distribution of nutrients, heavy metals, and PAHs affected by sediment dredging
      in the Wujin'gang River basin flowing into Meiliang Bay of Lake Taihu.
AB  - This paper's survey of the pollution of the Wujin'gang River is important because
      it is one of the main rivers flowing into Meiliang Bay of Lake Taihu in eastern
      China. Trace metals (TMs) in this paper are described according to their
      pollution index (P i). Cluster analysis and correlation analysis are utilized for
      group sites and to assess co-contamination. Toxicity effect analysis was
      conducted using individual sediment quality guideline quotients (SQGQs) and mean
      SQGQs. The results showed that sediment from the Wujin'gang River basin was
      affected by nutrients, heavy metals, and polycyclic aromatic hydrocarbons (PAHs),
      which are an essential contamination source for both Meiliang Bay and Zhushan Bay
      of Lake Taihu. The discharge of TMs has significant correlations to total
      nitrogen (TN) and total phosphorus (TP); however, no significant correlations
      were observed between the content of PAHs and TMs. Toxicity effect results show
      that sediment in the Wujin'gang River basin threatens sediment-dwelling
      organisms. The harmful effect was mainly caused by heavy metals especially Cd,
      Cr, Ni, and Cu. Sediment dredging is an effective way to control pollution from
      internal rivers especially for the pollution of TN and heavy metals in the
      Wujin'gang River basin. 

PMID- 24037298
TI  - Removal of non-steroidal anti-inflammatory drugs ibuprofen and ketoprofen from
      water by emulsion liquid membrane.
AB  - In this work, the removal of the worldwide non-steroidal anti-inflammatory drugs
      ibuprofen (IBP) and ketoprofen (KTP) by emulsion liquid membrane (ELM) was
      carried out. An ELM system is made up of hexane as diluent, Span 80 as the
      surfactant and sodium carbonate as the inner aqueous solution. Effect of
      experimental conditions that affect the extraction of IBP such as surfactant
      concentration, emulsification time, sulfuric acid concentration in external
      phase, acid type in external phase, internal phase concentration, type of
      internal phase, stirring speed, volume ratio of internal phase to membrane phase,
      treatment ratio, IBP initial concentration, diluent type and salt was
      investigated. The obtained results showed that by appropriate selection of the
      operational parameters, it was possible to extract nearly all of IBP molecules
      from the feed solution even in the presence of high concentration of salt. Under
      optimum operating conditions, the efficiencies of IBP removal from distilled
      water (99.3 %), natural mineral water (97.3 %) and sea water (94.0 %) were
      comparable, which shows that the ELM treatment process represents a very
      interesting advanced separation process for the removal of IBP from complex
      matrices such as natural and sea waters. Under the optimized experimental
      conditions, approximately 97.4 % KTP was removed in less than 20 min of contact
      time.

PMID- 24037300
TI  - Do urban canyons influence street level grass pollen concentrations?
AB  - In epidemiological studies, outdoor exposure to pollen is typically estimated
      using rooftop monitoring station data, whilst exposure overwhelmingly occurs at
      street level. In this study the relationship between street level and roof level
      grass pollen concentrations was investigated for city centre street canyon
      environments in Aarhus, Denmark, and London, UK, during the grass pollen seasons
      of 2010 and 2011 respectively. For the period mid-day to late evening, street
      level concentrations in both cities tended to be lower than roof-level
      concentrations, though this difference was found to be statistically significant
      only in London. The ratio of street/roof level concentrations was compared with
      temperature, relative humidity, wind speed and direction, and solar radiation.
      Results indicated that the concentration ratio responds to wind direction with
      respect to relative canyon orientation and local source distribution. In the
      London study, an increase in relative humidity was linked to a significant
      decrease in street/roof level concentration ratio, and a possible causative
      mechanism involving moisture mediated pollen grain buoyancy is proposed.
      Relationships with the other weather variables were not found to be significant
      in either location. These results suggest a tendency for monitoring station data
      to overestimate exposure in the canyon environment. 

PMID- 24037299
TI  - Evaluation of conventional, dynamic contrast enhanced and diffusion weighted MRI
      for quantitative Crohn's disease assessment with histopathology of surgical
      specimens.
AB  - OBJECTIVES: To prospectively compare conventional MRI sequences, dynamic contrast
      enhanced (DCE) MRI and diffusion weighted imaging (DWI) with histopathology of
      surgical specimens in Crohn's disease. METHODS: 3-T MR enterography was performed
      in consecutive Crohn's disease patients scheduled for surgery within 4 weeks. One
      to four sections of interest per patient were chosen for analysis. Evaluated
      parameters included mural thickness, T1 ratio, T2 ratio; on DCE-MRI maximum
      enhancement (ME), initial slope of increase (ISI), time-to-peak (TTP); and on DWI
      apparent diffusion coefficient (ADC). These were compared with location-matched
      histopathological grading of inflammation (AIS) and fibrosis (FS) using Spearman
      correlation, Kruskal-Wallis and Chi-squared tests. RESULTS: Twenty patients (mean
      age 38 years, 12 female) were included and 50 sections (35 terminal ileum, 11
      ascending colon, 2 transverse colon, 2 descending colon) were matched to AIS and
      FS. Mural thickness, T1 ratio, T2 ratio, ME and ISI correlated significantly with
      AIS, with moderate correlation (r = 0.634, 0.392, 0.485, 0.509, 0.525,
      respectively; all P < 0.05). Mural thickness, T1 ratio, T2 ratio, ME, ISI and ADC
      correlated significantly with FS (all P < 0.05). CONCLUSIONS: Quantitative
      parameters from conventional, DCE-MRI and DWI sequences correlate with
      histopathological scores of surgical specimens. DCE-MRI and DWI parameters
      provide additional information. KEY POINTS: * Conventional MR enterography can be
      used to assess Crohn's disease activity. * Several MRI parameters correlate with
      inflammation and fibrosis scores from histopathology. * Dynamic contrast enhanced
      imaging and diffusion weighted imaging give additional information. *
      Quantitative MRI parameters can be used as biomarkers to evaluate Crohn's disease
      activity.

PMID- 24037301
TI  - Caries and its risk factors in young children in five different countries.
AB  - The state of oral health plays an essential role in human comprehensive health.
      Nevertheless, although considerable improvement in oral health caries has been
      noted in both developed and newly developing countries, caries is still
      widespread among children. Although it can be monitored, caries cannot be
      properly eliminated. MATERIALS AND METHODS. This investigation, performed in
      cooperation with Jena Hospital in Germany, was conducted in five countries from
      2002-2008. The cities Riga (Latvia), Ouro Preto (Brazil), Erfurt (Germany),
      Volgograd (Russia) and Minsk (Belorus) were engaged in this investigation.
      Children at the age of 26-34 months were surveyed. Consistent with the research
      design, the mothers filled out questionnaires about the children's health, and an
      examination of the children's oral health was performed. The statistics program
      SPSS 15.0 was used to analyze the obtained data, and the correlations between
      changing findings were expressed by the Spearmen rank correlation coefficient
      (r). RESULTS. In this study, 472 children were observed: 179 from Riga, 152 from
      Erfurt, 62 from Ouru Preto, 116 from Minsk and 84 from Volgograd. A direct
      correlation existed between the country and plaque (r=0.16) and caries (dmft) (r=
      0.11). The direct correlation between dmft and Streptococcus mutans (r=-0.36) was
      characteristic of children from Erfurt. The lowest dmft index (0.62) was present
      in children from Erfurt, and the highest (1.57) in children from Ouro Preto.
      CONCLUSIONS. The frequency and prevalence of caries in young children in Riga is
      high; it was the lowest in Erfurt and the highest - in Brazil. Plaque and dt were
      one of the indices with a direct relationship in Riga, Brazil and Minsk. Poor
      oral hygiene, irregular tooth brushing and the consumption of cariogenic foods
      and drinks are the most important caries risk factors among children at the age
      of 2-3 years. The mother's knowledge and attitude affect the child's oral health.

PMID- 24037302
TI  - Prevalence of teeth number anomalies in orthodontic patients.
AB  - OBJECTIVES: The purpose of this study was to determine if the prevalence of teeth
      number anomalies (TNA) is more frequent in orthodontic patients than in common
      population and what is TNA clinical manifestation. MATERIAL AND METHODS: The
      records of 824 orthodontic patients (average age 15.22 years) from Orthodontic
      Clinic of Lithuanian University of Health Sciences were analyzed. The radiographs
      were analyzed by trained observer who followed a pre-established protocol:
      general observation of the teeth including third molar, followed by a systematic
      analysis of the erupted and unerupted teeth number in each quadrant. Descriptive
      statistics were performed for the study variables. A chi-square test was used to
      determine the difference in the prevalence of hypodontia between the genders. A
      value of P<0.05 was considered significant. RESULTS: The prevalence of hypodontia
      was 17.11 percent with no statistically significant difference between the
      genders (P>0.05). More frequently teeth were missing in the lower jaw: in the
      upper jaw - 10.3%, in the lower - 12.5% without statisticaly significant
      diference. Unilateral occurrence of dental agenesis was 1.5 times more common
      than bilateral occurrence. If more than one tooth was missing, usually other
      missing tooth was in the same group and in the same jaw. The upper and lower
      third molars were the most frequently missing teeth, followed by the mandibular
      second premolar. The prevalence of hyperdontia was 0.85 percent. Mesiodens was
      the most frequently found supernumerary tooth. CONCLUSIONS: It was found, that
      17.96% of orthodontic patients had teeth number anomalies. The upper and lower
      third molars were the most frequently missing teeth, followed by the mandibular
      second premolar. Hypodontia occurred more frequently than hyperdontia. Mesiodens
      was the most frequently found supernumerary tooth. The results confirm that TNA
      are more often found in orthodontic patients and these patients should be treated
      with multidisciplinary approach.

PMID- 24037303
TI  - Spring-bite: a new device for jaw motion rehabilitation. A case report.
AB  - The present paper describes the design features, potential indications and a
      clinical application of a newly designed device for jaw motion rehabilitation,
      the Spring-Bite. This device is characterized by a first class lever mechanism,
      which allows performing passive jaw motion rehabilitation at constant load
      without an active participation by the patient. Spring-Bite was developed for the
      management of temporomandibular joint (TMJ) hypomobility and its application may
      be much useful in the post-operatory phases of TMJ or orthognathic surgeries as
      well as in patients with reduced muscular force. 

PMID- 24037304
TI  - Extra-nodal primary diffuse large B-cell lymphoma of the maxilla. Fine needle
      aspiration cytology.
AB  - A 76-year-old female presented at University hospital of Crete with a large
      painless mass (d<10 cm) of the left maxilla. The cytologic diagnosis in FNAB
      smears was of a diffuse large B-cell lymphoma of the maxilla that was confirmed
      histologically. The fine needle aspiration cytology (FNAC) in conjunction with
      immunocytochemistry can distinguish between benign and malignant lymphoid
      infiltrates and support a diagnosis of extra-nodal diffuse large B-cell lymphoma.

PMID- 24037305
TI  - Keratoacanthoma in the inferior lip of an immunosuppressed patient. A case
      report.
AB  - Keratoacanthoma is a lesion typical crater, symmetrical, rounded, rapid growth
      with high potential for self-involution. The lesions may be multiple,
      disseminated and associated with some syndromes. The etiology of keratoacanthoma
      is not known, but it is often observed in patients chronically exposed to sun.
      Histopathological features of keratoacanthoma may resemble those of a well
      differentiated squamous cell carcinoma. The hallmark of the disease is
      spontaneous resolution after an intermediary stationary stage. The majority of
      the cases is treated by surgical excision. For this reason, very few cases have
      been documented until resolution, which constitutes the gold standard for this
      clinic diagnosis. The aim of this article is to report a case of keratoacanthoma
      in the inferior lip of an immunosuppressed patient. 

PMID- 24037306
TI  - Profiling of dynamic changes in the microbial community during the soy sauce
      fermentation process.
AB  - Soy sauce is a traditional condiment manufactured by natural inoculation and
      mixed culture fermentation. As is well known, it is the microbial community that
      plays an important role in the formation of its flavors. However, to date, its
      dynamic changes during the long period of fermentation process are still unclear,
      intensively constraining the improvement and control of the soy sauce quality. In
      this work, we revealed the dynamic changes of the microbial community by
      combining a cultured dependent method and a cultured independent method of
      polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis. Results
      indicated that the two methods verified and complemented each other in profiling
      microbial community, and that significant dynamics of the microbial community
      existed during the fermentation process, especially the strong inhibition of the
      growth of most of the microbes when entering into the mash stage from the koji
      stage. In the analysis of bacterial community, Staphylococcus and Bacillus were
      found to be the dominant bacteria and detected in the whole fermentation process.
      Kurthia and Klebsiella began to appear in the koji stage and then fade away in
      the early stage of the mash fermentation. In the analysis of fungal community,
      Aspergillus sojae and Zygosaccharomyces rouxii were found to be the dominant
      fungi in the koji and mash fermentation, respectively. It was clearly shown that
      when A. sojae decreased and disappeared in the middle stage of the mash
      fermentation, Z. rouxii appeared and increased at the meantime. Aspergillus
      parasiticus, Trichosporon ovoides and Trichosporon asahii also appeared in the
      koji and the early period of the mash fermentation and disappeared thereafter.
      Similar to Z. rouxii, Millerozyma farinosa and Peronospora farinosa were also
      found spontaneously which appeared in the mid-late period of the mash
      fermentation. The principal component analysis suggested that the microbial
      community underwent significant changes in the early period of the fermentation
      and, thereafter, tended to the stabilization in the mid-late periods. This study
      gave us important clues to understand the fermentation process and can serve as a
      foundation for improving the quality of soy sauce in the future.

PMID- 24037307
TI  - Construction of engineered Arthrobacter simplex with improved performance for
      cortisone acetate biotransformation.
AB  - Arthrobacter simplex 156 is a microorganism that is used for steroid drug
      biotransformation of cortisone acetate (CA) to prednisone acetate (PA). The
      enzyme 3-ketosteroid-?(1)-dehydrogenase encoded by the ksdD gene plays an
      important role in the bioconversion process. To further improve the
      biotransformation efficiencies of the industrial strain, a genetic manipulation
      system for A. simplex 156 was developed. Additional copies of the ksdD gene under
      the control of the cat promoter (from pXMJ19) were transferred into the strain A.
      simplex 156 and integrated into the 16S rDNA sites, yielding a series of
      recombinant strains. One of these recombinant strains, designated A. simplex
      M158, exhibited superior properties for CA biotransformation. At the substrate
      concentration of 83.6 g/l, the highest PA production of the recombinant strain
      reached 66.7 g/l, which is approximately 32.9 % higher than that of wild-type
      strains, and the incubation time for CA to PA bioconversion was reduced by 20 h.
      Southern blotting analysis of the recombinant strain indicated two copies of
      deregulated ksdD genes were integrated into the 16S rDNA sites, which means two
      of five 16S rRNA operons were insertionally disrupted in the recombinant strain.
      However, the disruption of the two 16S rRNA operons did not affect the growth
      rate of the recombinant strain, which survived and thrived under desired
      conditions. In addition, the new strain was genetically stable for more than 100
      generations without the use of antibiotics for selection. These superior
      characteristics make the new strain more suitable than the wild-type strain for
      PA production.

PMID- 24037308
TI  - The DprE1 enzyme, one of the most vulnerable targets of Mycobacterium
      tuberculosis.
AB  - The re-emergence of tuberculosis in recent years led the World Health
      Organization (WHO) to launch the Stop TB Strategy program. Beside repurposing the
      existing drugs and exploring novel molecular combinations, an essential step to
      face the burden of tuberculosis will be to develop new drugs by identifying
      vulnerable bacterial targets. Recent studies have focused on decaprenylphosphoryl
      D-ribose oxidase (DprE1) of Mycobacterium tuberculosis, an essential enzyme
      involved in cell wall metabolism, for which new promising molecules have proved
      efficacy as antitubercular agents. This review summarizes the state of the art
      concerning DprE1 in terms of structure, enzymatic activity and inhibitors. This
      enzyme is emerging as one of the most vulnerable target in M. tuberculosis.

PMID- 24037309
TI  - Ice recrystallization inhibition mediated by a nuclear-expressed and -secreted
      recombinant ice-binding protein in the microalga Chlamydomonas reinhardtii.
AB  - A Lolium perenne ice-binding protein (LpIBP) demonstrates superior ice
      recrystallization inhibition (IRI) activity and has proposed applications in
      cryopreservation, food texturing, as well as in being a "green" gas hydrate
      inhibitor. Recombinant production of LpIBP has been previously conducted in
      bacterial and yeast systems for studies of protein characterization, but large
      scale applications have been hitherto limited due to high production costs. In
      this work, a codon-optimized LpIBP was recombinantly expressed and secreted in a
      novel one-step vector system from the nuclear genome of the green microalga
      Chlamydomonas reinhardtii. Both mixotrophic and photoautotrophic growth regimes
      supported LpIBP expression, indicating the feasibility of low-cost production
      using minimal medium, carbon dioxide, and light energy as input. In addition,
      multiple growth and bioproduct extraction cycles were performed by repetitive
      batch cultivation trials, demonstrating the potential for semi-continuous
      production and biomass harvesting. Concentrations of recombinant protein reached
      in this proof of concept approach were sufficient to demonstrate IRI activity in
      culture media without additional purification or concentration, with activity
      further verified by thermal hysteresis and morphology assays. The incorporation
      of the recombinant LpIBP into a model gas hydrate offers the promise that algal
      production may eventually find application as a "green" hydrate inhibitor. 

PMID- 24037310
TI  - The up-regulation of cysteine-rich protein 61 induced by transforming growth
      factor beta enhances osteosarcoma cell migration.
AB  - Overexpressed cysteine-rich protein 61 (Cyr61) is believed to enhance
      osteosarcoma (OS) cell metastasis, but the mechanism of Cyr61 overexpression in
      OS is not clear so far. In this study 33 OS samples were analyzed by
      immunostaining and focused on two parts: the correlation between overexpression
      of Cyr61 and OS metastasis; the mechanism of regulating Cyr61 expression in OS.
      Twenty-five out of 33 cases (75.76 %) with metastasis showed high expression of
      Cyr61. Furthermore, Cyr61 expression in Saos-2 cells was reduced by siRNA, and
      lower expression of Cyr61 in Saos-2 cell resulted in a cell migration deficiency
      and had no effect on cell proliferation. Particularly, Cyr61 expression was
      significantly increased in Saos-2 cells in response to different dosages of
      transforming growth factor beta (TGF-beta), indicating that the expression of
      Cyr61 is TGF-beta dependent. A transwell assay showed that Saos-2 cells
      stimulated with TGF-beta had a greater capacity for migration than the control
      cells. The p38 MAPK-specific inhibitor SB203580 was able to reduce Cyr61
      expression and inhibit the migration of Saos-2 cells stimulated with TGF-beta.
      These results obtained provide new evidence that overexpressed Cyr61 plays a key
      role in the metastasis of OS cells and Cyr61 is a potential target downstream of
      TGF-beta/p38 MAPK to regulate cell migration. 

PMID- 24037311
TI  - Current advances in single-port laparoscopic surgery.
AB  - PURPOSE: Single-port laparoscopic surgery has the intention to further minimize
      the access trauma similar to natural orifice transluminal endoscopic surgery.
      While special trocars and instruments are needed, the spectrum of clinical
      indications corresponds to the conventional laparoscopic surgery. This review
      gives an overview of the current applications and advances in single-port
      laparoscopic surgery. METHODS: The PubMed database was searched for "single
      incision laparoscopic surgery" or "single port" and different operations (e.g.,
      cholecystectomy, colectomy, and appendectomy). The references and our own
      experiences were considered for historic development and current advances.
      RESULTS: The spreading of single-port laparoscopic surgery is not as fast as
      expected. References show that operations using a single-port technique are
      feasible, safe, and efficient. More technical difficulties for the surgeon and
      higher costs must be considered. A better cosmetic result, less postoperative
      pain, and a faster recovery could be potential benefits for the patients.
      CONCLUSIONS: Current advances in single-port laparoscopic surgery are difficult
      to define. The most common procedures are single-port laparoscopic
      cholecystectomies, colectomies, and appendectomies. Significant clinical benefits
      have not yet been proven even in prospective, randomized studies.

PMID- 24037312
TI  - Evaluation of short-term and long-term results after laparoscopic antireflux
      surgery: esophageal manometry and 24-h pH monitoring versus quality of life
      index.
AB  - PURPOSE: The objective of this long-term study is to compare data on
      postoperative quality of life with objective functional measurements in patients
      with gastroesophageal reflux disease who have undergone laparoscopic antireflux
      surgery. METHODS: Between 1995 and 2005, 162 patients with gastroesophageal
      reflux disease underwent laparoscopic surgery. A minimum of 4 years after
      surgery, 60 patients were contacted at random, 29 of whom agreed to follow-up
      examination. The following examinations were performed preoperatively, 6 months
      postoperatively, and 4-12 years postoperatively: esophageal manometry, 24-h
      gastroesophageal pH-metry, and assessment of patient quality of life based on the
      gastrointestinal quality of life index (GIQLI). RESULTS: The number of
      postsurgical reflux episodes was reduced significantly, both at 6 months and at 4
      or more years after surgery. The number of episodes dropped from 183 before
      surgery to 58 at 6 months after surgery and remained constant >= 4 years later.
      Surgery also produced a significant drop in reflux time, seen both 6 months and
      >= 4 years later. Six months after surgery, the median reflux time had fallen
      from 134 min (preoperatively) to 27 min, and at >= 4 years it was still
      significantly reduced at 35 min. Sphincter length (median preoperative length, 3
      cm; median postoperative length (at 6 months and at >= 4 years), 4 cm) and
      sphincter pressure (median preoperative pressure, 3 mmHg; median at 6 months, 12
      mmHg; median at >= 4 years, 10.9 mmHg) were significantly improved by surgery as
      well. Finally, surgery produced an improvement in quality of life. The median
      preoperative GIQLI was 102, while at 6 months after surgery it was 113 and at >=
      4 years after surgery it was 124. CONCLUSION: Laparoscopic fundoplication
      guarantees long-term improvement in symptoms and quality of life for patients
      suffering from gastroesophageal reflux disease. The effectiveness of reflux
      surgery can thus be demonstrated by long-term quality of life assessments and
      postoperative functional measurements. No statistically significant correlation
      between total score (DeMeester) and GIQLI could be demonstrated.

PMID- 24037313
TI  - Race/ethnic difference in diabetes and diabetic complications.
AB  - Health disparities in diabetes and its complications and comorbidities exist
      globally. A recent Endocrine Society Scientific Statement described the Health
      Disparities in several endocrine disorders, including type 2 diabetes. In this
      review, we summarize that statement and provide novel updates on race/ethnic
      differences in children and adults with type 1 diabetes, children with type 2
      diabetes, and in Latino subpopulations. We also review race/ethnic differences in
      the epidemiology of diabetes, prediabetes, and diabetes complications and
      mortality in the United States and globally. Finally, we discuss biological,
      behavioral, social, environmental, and health system contributors to diabetes
      disparities to identify areas for future preventive interventions. 

PMID- 24037314
TI  - Is double-bundle anterior cruciate ligament reconstruction superior to single
      bundle? A comprehensive systematic review.
AB  - PURPOSE: To describe current evidence on single- and double-bundle anterior
      cruciate ligament (ACL) reconstruction, in terms of differences in knee
      kinematics, functional outcomes, patient-reported outcomes and graft failures.
      METHODS: An electronic search was made using PubMed (MEDLINE), EMBASE and
      Cochrane Library. Studies published from January 1995 to August 2011 were
      included, and an updated search was made in PubMed in July 2012. Therapeutic
      studies, level of evidence I-III, for isolated primary ACL tears written in
      English comparing single- and double-bundle reconstruction reporting clinical
      outcome were included. Quality appraisal based on Cochrane Collaboration's tool
      for assessing risk of bias was performed. RESULTS: Of 7,154 potentially eligible
      studies, 60 papers were included (25 randomised controlled trials, 21 prospective
      comparative studies, 14 retrospective comparative studies), comprising 4,146
      patients (2,072 single-bundle, 2,074 double-bundle). Minor differences were found
      between study types. An analysis of graft failures revealed fewer re-ruptures in
      double-bundle reconstruction than single-bundle, 19 and 44, respectively. Up to
      45 % of the studies reported a superior outcome in double-bundle reconstruction
      in terms of antero-posterior laxity, measured with the Lachman, anterior drawer,
      KT-1000/2000 and navigation. Measurements of rotatory laxity revealed superior
      results in double-bundle reconstruction measured with pivot shift and navigation
      in 18/42 (8/15 anatomically reconstructed) and 9/20 studies, respectively.
      Patient-reported outcome measures and functional outcomes did not differ to a
      large extent; however, differences when identified were almost exclusively in
      favour of double-bundle reconstruction. CONCLUSION: Based on current evidence,
      double-bundle reconstruction appears to have fewer re-ruptures and less antero
      posterior and rotatory laxity. Furthermore, no differences were found in short
      term patient-reported outcome measures or objective findings. However, detailed
      statistical analyses of the included studies divided into homogeneous groups are
      needed to avoid reporting bias and to confirm any statistical difference.

PMID- 24037315
TI  - Bisected, complex N-glycans and galectins in mouse mammary tumor progression and
      human breast cancer.
AB  - Bisected, complex N-glycans on glycoproteins are generated by the
      glycosyltransferase MGAT3 and cause reduced cell surface binding of galectins.
      Previously, we showed that MGAT3 reduces growth factor signaling and retards
      mammary tumor progression driven by the Polyoma middle T antigen (PyMT) expressed
      in mammary epithelium under the mouse mammary tumor virus (MMTV) promoter.
      However, the penetrance of the tumor phenotype became variable in mixed FVB/N and
      C57BL/6 female mice and we therefore investigated a congenic C57BL/6 Mgat3(-/
      )/MMTV-PyMT model. In the absence of MGAT3, C57BL/6 Mgat3(-/-)/MMTV-PyMT females
      exhibited accelerated tumor appearance and increased tumor burden, glucose uptake
      in tumors and lung metastasis. Nevertheless, activation of extracellular signal
      regulated kinase (ERK)1/2 or protein kinase B (AKT) was reduced in ~20-week
      C57BL/6 MMTV-PyMT tumors lacking MGAT3. Activation of focal adhesion kinase
      (FAK), protein tyrosine kinase Src, and p38 mitogen-activated protein kinase were
      similar to that of controls. All the eight mouse galectin genes were expressed in
      mammary tumors and tumor epithelial cells (TECs), but galectin-2 and -12 were not
      detected by western analysis in tumors, and galectin-7 was not detected in 60% of
      the TEC lines. From microarray data reported for human breast cancers, at least
      10 galectin and 7 N-glycan N-acetylglucosaminyl (GlcNAc)-transferase (MGAT) genes
      are expressed in tumor tissue, and expression often varies significantly between
      different breast cancer subtypes. Thus, in summary, while MGAT3 and bisected
      complex N-glycans retard mouse mammary tumor progression, genetic background may
      modify this effect; identification of key galectins that promote mammary tumor
      progression in mice is not straightforward because all the eight galectin genes
      are expressed; and high levels of MGAT3, galectin-4, -8, -10, -13 and -14
      transcripts correlate with better relapse-free survival in human breast cancer. 

PMID- 24037317
TI  - Humanitarian surgery: a call to action for anesthesiologists.

PMID- 24037321
TI  - A critical care holiday poem.

PMID- 24037316
TI  - Critical role of interleukin-11 in isoflurane-mediated protection against
      ischemic acute kidney injury in mice.
AB  - BACKGROUND: Isoflurane releases renal tubular transforming growth factor-beta1
      (TGF-beta1) and protects against ischemic acute kidney injury. Recent studies
      suggest that TGF-beta1 can induce a cytoprotective cytokine interleukin (IL)-11.
      In this study, the authors tested the hypothesis that isoflurane protects against
      ischemic acute kidney injury by direct induction of renal tubular IL-11
      synthesis. METHODS: Human kidney proximal tubule cells were treated with 1.25
      2.5% isoflurane or carrier gas (room air + 5% carbon dioxide) for 0-16 h. The
      authors also anesthetized C57BL/6 mice with 1.2% isoflurane or with
      equianesthetic dose of pentobarbital for 4 h. In addition, the authors subjected
      IL-11 receptor (IL-11R) wild-type, IL-11R-deficient, or IL-11 neutralized mice to
      30-min renal ischemia followed by reperfusion under 4 h of anesthesia with
      pentobarbital or isoflurane (1.2%). RESULTS: Isoflurane increased IL-11 synthesis
      in human (approximately 300-500% increase, N = 6) and mouse (23 +/- 4 [mean +/-
      SD] fold over carrier gas group, N = 4) proximal tubule cells that were
      attenuated by a TGF-beta1-neutralizing antibody. Mice anesthetized with
      isoflurane showed significantly increased kidney IL-11 messenger RNA (13.8 +/- 2
      fold over carrier gas group, N = 4) and protein (31 +/- 9 vs. 18 +/- 2 pg/mg
      protein or approximately 80% increase, N = 4) expression compared with
      pentobarbital-anesthetized mice, and this increase was also attenuated by a TGF
      beta1-neutralizing antibody. Furthermore, isoflurane-mediated renal protection in
      IL-11R wild-type mice was absent in IL-11R-deficient mice or in IL-11R wild-type
      mice treated with IL-11-neutralizing antibody (N = 4-6). CONCLUSION: In this
      study, the authors suggest that isoflurane induces renal tubular IL-11 via TGF
      beta1 signaling to protect against ischemic acute kidney injury.

PMID- 24037322
TI  - Artificial spin ice: Crystal-clear order.

PMID- 24037323
TI  - Halostable cellulase with organic solvent tolerance from Haloarcula sp. LLSG7 and
      its application in bioethanol fermentation using agricultural wastes.
AB  - A haloarchaeal strain LLSG7 with cellulolytic activity was isolated from the
      saline soil of Yuncheng Salt Lake, China. Biochemical and physiological
      characterization along with 16S rRNA gene sequence analysis placed the isolate in
      the genus Haloarcula. Cellulase production was strongly influenced by the
      salinity of the culture medium with the maximum obtained in the presence of 25 %
      NaCl. Substrate specificity tests showed that the crude cellulase was a
      multicomponent enzyme system, and zymogram analysis revealed that five different
      endoglucanases were secreted by strain LLSG7. Optimal cellulase activity was at
      50  degrees C, pH 8.0, and 20 % NaCl. In addition, it was highly active and
      stable over broad ranges of temperature (40-80  degrees C), pH (7.0-11.0), and
      NaCl concentration (17.5-30 %). The cellulase displayed remarkable stability in
      the presence of non-polar organic solvents with log P ow >= 1.97. The crude
      cellulase secreted by strain LLSG7 was further applied to hydrolyze alkali
      pretreated rice straw and the enzymatic hydrolysate was used as the substrate for
      bioethanol fermentation by Saccharomyces cerevisiae. The yield of ethanol was
      0.177 g per gram of pretreated rice straw, suggesting that it might be
      potentially useful for bioethanol production. 

PMID- 24037324
TI  - A non-nucleoside triphosphate for powering kinesin-microtubule motility with
      photo-tunable velocity.
AB  - Three non-nucleoside triphosphates, one containing an azobenzene moiety, power a
      kinesin-microtubule system with high motile activity, with an observed maximum
      velocity of almost half of that obtained with ATP. The cis-trans
      photoisomerization of the azobenzene unit allows reversible and repeated control
      over the motile properties of kinesin. 

PMID- 24037326
TI  - Alternating-laser excitation: single-molecule FRET and beyond.
AB  - The alternating-laser excitation (ALEX) scheme continues to expand the
      possibilities of fluorescence-based assays to study biological entities and
      interactions. Especially the combination of ALEX and single-molecule Forster
      Resonance Energy Transfer (smFRET) has been very successful as ALEX enables the
      sorting of fluorescently labelled species based on the number and type of
      fluorophores present. ALEX also provides a convenient way of accessing the
      correction factors necessary for determining accurate molecular distances. Here,
      we provide a comprehensive overview of the concept and current applications of
      ALEX and we explicitly discuss how to obtain fully corrected distance information
      across the entire FRET range. We also present new ideas for applications of ALEX
      which will push the limits of smFRET-based experiments in terms of temporal and
      spatial resolution for the study of complex biological systems. 

PMID- 24037325
TI  - Distinctive features of microsaccades in Alzheimer's disease and in mild
      cognitive impairment.
AB  - During visual fixation, the eyes are never completely still, but produce small
      involuntary movements, called "fixational eye movements," including
      microsaccades, drift, and tremor. In certain neurological disorders, attempted
      fixation results in abnormal fixational eye movements with distinctive
      characteristics. Thus, determining how normal fixation differs from pathological
      fixation has the potential to aid early and differential noninvasive diagnosis of
      neurological disease as well as the quantification of its progression and
      response to treatment. Here, we recorded the eye movements produced by patients
      with Alzheimer's disease, patients with mild cognitive impairment, and healthy
      age-matched individuals during attempted fixation. We found that microsaccade
      magnitudes, velocities, durations, and intersaccadic intervals were comparable in
      the three subject groups, but microsaccade direction differed in patients versus
      healthy subjects. Our results indicate that microsaccades are more prevalently
      oblique in patients with Alzheimer's disease or mild cognitive impairment than in
      healthy subjects. These findings extended to those microsaccades paired in square
      wave jerks, supporting the hypothesis that microsaccades and square-wave jerks
      form a continuum, both in healthy subjects and in neurological patients. 

PMID- 24037328
TI  - Choosing the correct accessory for each stoma type: an update.
AB  - There are many people with a stoma that report a good quality of life. However,
      for many, problems can be encountered that can directly affect them. The use of a
      stoma accessory, in addition to the stoma appliance, can often benefit people
      with a stoma in relation to treating sore skin or preventing appliances from
      leakage. This article focuses on some of the more common stoma accessories,
      including when and why they should be used. 

PMID- 24037327
TI  - ATP-sensitive potassium currents from channels formed by Kir6 and a modified
      cardiac mitochondrial SUR2 variant.
AB  - Cardiac ATP-sensitive potassium channels (KATP) are found in both the
      sarcoplasmic reticulum (sarcKATP) and the inner membrane of mitochondria
      (mitoKATP). SarcKATP are composed of a pore containing subunit Kir6.2 and a
      regulatory sulfonylurea receptor subunit (SUR2), but the composition of mitoKATP
      remains unclear. An unusual intra-exonic splice variant of SUR2 (SUR2A-55) was
      previously identified in mitochondria of mammalian heart and brain, and by
      analogy with sarcKATP we proposed SUR2A-55 as a candidate regulatory subunit of
      mitoKATP. Although SUR2A-55 lacks the first nucleotide binding domain (NBD) and 2
      transmembrane domains (TMD), it has a hybrid TMD and retains the second NBD. It
      resembles a hemi-ABC transporter suggesting it could multimerize to function as a
      regulatory subunit. A putative mitochondrial targeting signal in the N-terminal
      domain of SUR2A-55 was removed by truncation and when co-expressed with Kir6.1
      and Kir6.2 it targeted to the plasma membrane and yielded KATP currents. Single
      channel conductance, mean open time, and burst open time of SUR2A-55 based KATP
      was similar to the full-length SUR2A based KATP. However, the SUR2A-55 KATP were
      70-fold less sensitive to block by ATP, and twice as resistant to intracellular
      Ca (2+) inhibition compared with the SUR2A KATP, and were markedly insensitive to
      KATP drugs, pinacidil, diazoxide, and glybenclamide. These results suggest that
      the SUR2A-55 based channels would tend to be open under physiological conditions
      and in ischemia, and could account for cardiac and mitochondrial phenotypes
      protective for ischemia. 

PMID- 24037329
TI  - Caring for people with arthritis and a stoma.
AB  - It is understood that 10 million people currently live with arthritis and that
      there are two main types: osteoarthritis and rheumatoid arthritis (Arthritis
      Care, 2013). As the numbers of people with arthritis grows, and the population
      ages, it is likely that nurses may be presented with increasing numbers of people
      who require advice, not only when they have their stoma fashioned, but later in
      their life. The purpose of this article is to consider the impact of arthritis
      upon stoma care and make practical suggestions for stoma management. Sources of
      further help and information for people living with a stoma and arthritis have
      also been included. It is hoped that by reading this article the nurse will be
      more familiar with the impact that arthritis may have on a person with a stoma
      and how they can be assisted to manage as independently as possible. 

PMID- 24037330
TI  - Managing high-output stomas: module 2 of 3.

PMID- 24037331
TI  - Quality of life following ileoanal pouch failure.
AB  - This article describes a novel qualitative study exploring the lived experience
      of participants having undergone ileoanal pouch failure, on a background of
      ulcerative colitis (UC). It focuses on the impact of living with indefinite
      diversion of the pouch and a permanent end ileostomy. Six participants were
      interviewed with an aim to establish their experience of pouch failure and the
      support they required. Five pertinent themes emerged that suggested participants
      did not expect pouch failure and were unprepared for the regression towards UC.
      Some participants recommenced drug therapy, wore pads to manage leakage from the
      diverted pouch, avoided certain social settings or manipulated diet and lifestyle
      in order to gain an acceptable quality of life with a permanent ileostomy. Pouch
      failure potentially presents adverse effects on patients' quality of life, but
      currently there is a deficit in support and resources available in order to
      provide acceptable outcomes for patients experiencing pouch failure. 

PMID- 24037332
TI  - Convex stoma appliances: are we getting it right?

PMID- 24037333
TI  - Home delivery: a valuable service.

PMID- 24037334
TI  - Patients' experiences of pancaking while living with a colostomy: a survey.
AB  - Anecdotally, pancaking is recognised as troublesome within stoma care, leaving
      many people with ostomies feeling exasperated in trying to deal with this
      difficult problem. Stoma care nurses offer strategies to help alleviate it, but
      when strategies fail and appliances continue to leak, or require changing owing
      to risk of leaking, individuals often feel helpless, demoralised and quality of
      life can be damaged. A postal survey was carried out to try and identify some of
      the issues relating to pancaking. Eighty two percent of respondents were likely
      to experience some degree of pancaking and an alarming 58% changed their pouch
      more often as a management technique. Therefore, as a consequence of pancaking,
      the health economy is affected because each individual who suffers from pancaking
      uses a higher number of appliances. This results in increased costs for the NHS.
      There is currently no published research regarding pancaking, meaning an
      integrated approach to finding solutions is needed. 

PMID- 24037335
TI  - Predictors of septic shock in obstructive acute pyelonephritis.
AB  - PURPOSE: Acute pyelonephritis (APN) with obstructive uropathy is not uncommon and
      often causes serious conditions including sepsis and septic shock. We assessed
      the risk factors for septic shock in patients with obstructive APN associated
      with upper urinary tract calculi. METHODS: We retrospectively studied 69 patients
      with obstructive APN associated with upper urinary tract calculi who were
      admitted to our hospital. Emergency drainage for decompression of the renal
      collecting system was performed for empirical treatment in cases of failure of
      initial treatment and for severe cases. We assessed the risk factors for septic
      shock by multivariate logistic regression analysis. RESULTS: Overall, 45 patients
      (65.2 %) underwent emergency drainage and 23 (33.3 %) patients showed septic
      shock. Poor performance status and the presence of diabetes mellitus (DM) in the
      septic shock group were more common than in the non-septic shock group (p = 0.012
      and p = 0.011, respectively). The platelet count and serum albumin level in the
      septic shock group were significantly lower than in the non-septic shock group (p
      = 0.002 and p = 0.003, respectively). Positive rates of midstream urine culture
      and blood culture in the septic shock group were significantly higher than in the
      non-septic shock group (p = 0.022 and p = 0.001, respectively). Multivariate
      analysis showed that decreases in the platelet count (OR 5.43, p = 0.014) and
      serum albumin level (OR 5.88, p = 0.023) were independent risk factors for septic
      shock. CONCLUSION: Patients with obstructive APN associated with upper urinary
      tract calculi who have decreases in platelet count and serum albumin level should
      be treated with caution against the development of septic shock.

PMID- 24037336
TI  - Extraperitoneal transumbilical laparoendoscopic single-site radical prostatectomy
      using a homemade single-port device: 20 cases with midterm outcomes.
AB  - PURPOSE: To describe the surgical technique and to report the midterm outcomes of
      laparoendoscopic single-site radical prostatectomy (LESS-RP) with a homemade
      single-port device. METHODS: Between August 2009 and October 2011, 20 LESS-RP
      procedures were performed in a single center by a high-volume surgeon. The
      surgical methods are outlined in the paper. Preoperative, perioperative,
      pathologic, midterm oncological, and functional outcomes data were analyzed.
      RESULTS: On average, patients were 66.1 years old, had a mean body mass index of
      24.4 kg/m(2), and a mean prostate-specific antigen (PSA) value of 12.2 ng/ml. No
      conversion was required; however, a single additional 5-mm port was required in
      one case. The mean operative time was 248 min; mean estimated blood loss was 94
      ml. The mean visual analog pain score at day 3 was 1.5 out of 10, and the mean
      hospital stay was 15.4 day. Pathology showed one focal positive margin (5 %) in a
      T3a patient, and mean Gleason score was 6.7. There were a total of four Clavien
      grade 2 complications. The median follow-up was 22.8 month (range 12-36 month).
      No PSA recurrence was detected during follow-up period; the potency rate after
      bilateral neurovascular bundle preservation was 60 % (3/5). Complete continence
      recovery (no pad) was observed in 85 % of the patients at 1 year, in 90 % at 2
      years, and in all three patients at 3 years. CONCLUSIONS: LESS-RP is technically
      feasible and safe, with excellent cosmesis, low postoperative pain levels, and
      acceptable midterm oncological, and functional outcomes. Comparative
      investigation to conventional LRP is needed.

PMID- 24037337
TI  - Synthetic modification of salinomycin: selective O-acylation and biological
      evaluation.
AB  - Salinomycin has found renewed interest as an agent for prevention of cancer
      recurrence through selectively targeting cancer stem cells. Strategies for
      generation of improved salinomycin analogs by individual modification of its
      hydroxyl groups are presented. An evaluation of the dose-response effects of the
      resulting library on breast cancer cell lines shows that acylation of the C20
      hydroxyl can be used to improve IC50 values down to one fifth that of
      salinomycin. 

PMID- 24037338
TI  - Rod fracture after long construct fusion for spinal deformity: clinical and
      radiographic risk factors.
AB  - BACKGROUND: No reports have been published on detailed risk factors for rod
      fracture after spinal deformity correction and fusion. The purpose of this study
      was to analyze clinical and radiographic risk factors of rod fracture after long
      construct fusion for spinal deformity. METHODS: The survey subjects were 155
      cases who were diagnosed with spinal deformity and underwent correction and
      fusion surgery with long construct instrumentation (>3 levels, average 10.3
      levels) between July 2004 and June 2010. The subjects comprised 32 males and 123
      females with a mean age of 19.0 (range 8-78) years. The mean Cobb angle was 61.0
      +/- 16.1 degrees  preoperatively and 25.7 +/- 16.9 degrees  postoperatively.
      Univariate analysis and logistic regression analysis were performed. RESULTS: Rod
      fracture occurred in 8 of 155 cases (5.2 %). The mean period from surgery to rod
      fracture was 18.1 months (range 2-37). The level of fracture ranged from the
      thoracolumbar junction to the lumbosacral vertebrae. Six patients had fracture
      near the fused lower end and two patients had fracture at the thoracolumbar
      junction. Univariate analysis revealed that non-ambulatory status, preoperative
      kyphosis, small-diameter rods, multiple surgery, and use of iliac screws were
      significant risk factors for rod fracture. Sex, obesity, severity of preoperative
      scoliosis, and rod material were not significant risk factors. Logistic
      regression analysis revealed that use of iliac screws (odds ratio: 81.9, 95 %
      confidence interval: 7.2-935.0, p < 0.001) and small-diameter (<6 mm) rods (odds
      ratio: 16.3, 95 % confidence interval: 1.7-152.6, p = 0.015) were risk factors
      for rod fracture. CONCLUSIONS: The incidence of rod fracture after long construct
      fusion for spinal deformity was 5.2 %. Iliac screw fixation and small-diameter
      rods were risk factors for rod fracture.

PMID- 24037339
TI  - Epidermal CCL27 expression is regulated during skin development and keratinocyte
      differentiation.

PMID- 24037340
TI  - Changing incidence trends of cutaneous B-cell lymphoma.

PMID- 24037341
TI  - Epidermal deletion of HIF-2alpha stimulates wound closure.
AB  - Wound closure requires a complex series of micro-environmentally influenced
      events. A key aspect of wound closure is the migration of keratinocytes across
      the open wound. It has been found previously that the response to hypoxia via the
      HIF-1alpha transcription factor is a key feature of wound closure. The need for
      hypoxic response is likely due to interrupted wound vasculature, as well as
      infection, and in this work we investigated the need for a highly related hypoxic
      response transcription factor, HIF-2alpha. This factor was deleted tissue
      specifically in mice, and the resulting mice were found to have an accelerated
      rate of wound closure. This is correlated with a reduced bacterial load and
      inflammatory response in these mice. This indicates that manipulating or reducing
      the HIF-2alpha response in keratinocytes could be a useful means to accelerate
      wound healing and tissue repair. 

PMID- 24037342
TI  - Dominant effects of Delta40p53 on p53 function and melanoma cell fate.
AB  - The TP53 gene encodes 12 distinct isoforms, some of which can alter p53 activity
      in the absence of genomic alteration. Endogenous p53 isoforms have been
      identified in cancers; however, the function of these isoforms remains unclear.
      In melanoma, the frequency of TP53 mutations is relatively low compared with
      other cancers, suggesting that these isoforms may have a larger role in
      regulating TP53 activity. We hypothesized that p53 function and therefore cell
      fate might be altered by the presence of Delta40p53, an embryonic isoform missing
      the first 40 N-terminal amino acids of the full-length protein including the
      transactivation and Mdm2-binding domains. To test this hypothesis, we transduced
      tumor and normal cells with a lentivirus encoding Delta40p53. We found that
      exogenous Delta40p53 caused apoptosis and increased the levels of endogenous,
      activated p53 in both cancerous and non-cancerous cells, which led to significant
      levels of cell death, particularly in cancer cells. Activated p53 molecules
      formed nuclear heterotetramers with Delta40p53 and altered downstream p53
      transcription target levels including p53-induced protein with death domain and
      cyclin-dependent kinase inhibitor, p21. Delta40p53 altered the promoter occupancy
      of these downstream p53 target genes in such a way that it shifted cell fate
      toward apoptosis and away from cell cycle arrest. We show that tumor suppression
      by p53 can occur via an alternate route that relies on its interaction with
      Delta40p53. 

PMID- 24037343
TI  - Identification of genes promoting skin youthfulness by genome-wide association
      study.
AB  - To identify genes that promote facial skin youthfulness (SY), a genome-wide
      association study on an Ashkenazi Jewish discovery group (n=428) was performed
      using Affymetrix 6.0 Single-Nucleotide Polymorphism (SNP) Array. After SNP
      quality controls, 901,470 SNPs remained for analysis. The eigenstrat method
      showed no stratification. Cases and controls were identified by global facial
      skin aging severity including intrinsic and extrinsic parameters. Linear
      regression adjusted for age and gender, with no significant differences in
      smoking history, body mass index, menopausal status, or personal or family
      history of centenarians. Six SNPs met the Bonferroni threshold with Pallele<10(
      8); two of these six had Pgenotype<10(-8). Quantitative trait loci mapping
      confirmed linkage disequilibrium. The six SNPs were interrogated by MassARRAY in
      a replication group (n=436) with confirmation of rs6975107, an intronic region of
      KCND2 (potassium voltage-gated channel, Shal-related family member 2)
      (Pgenotype=0.023). A second replication group (n=371) confirmed rs318125,
      downstream of DIAPH2 (diaphanous homolog 2 (Drosophila)) (Pallele=0.010,
      Pgenotype=0.002) and rs7616661, downstream of EDEM1 (ER degradation enhancer,
      mannosidase alpha-like 1) (Pgenotype=0.042). DIAPH2 has been associated with
      premature ovarian insufficiency, an aging phenotype in humans. EDEM1 associates
      with lifespan in animal models, although not humans. KCND2 is expressed in human
      skin, but has not been associated with aging. These genes represent new candidate
      genes to study the molecular basis of healthy skin aging. 

PMID- 24037345
TI  - Spatial heterogeneity in the timing of birch budburst in response to future
      climate warming in Ireland.
AB  - In order to predict the impact of future climate warming on trees it is important
      to quantify the effect climate has on their development. Our understanding of the
      phenological response to environmental drivers has given rise to various
      mathematical models of the annual growth cycle of plants. These models simulate
      the timing of phenophases by quantifying the relationship between development and
      its triggers, typically temperature. In addition, other environmental variables
      have an important role in determining the timing of budburst. For example,
      photoperiod has been shown to have a strong influence on phenological events of a
      number of tree species, including Betula pubescens (birch). A recently developed
      model for birch (DORMPHOT), which integrates the effects of temperature and
      photoperiod on budburst, was applied to future temperature projections from a 19
      member ensemble of regional climate simulations (on a 25 km grid) generated as
      part of the ENSEMBLES project, to simulate the timing of birch budburst in
      Ireland each year up to the end of the present century. Gridded temperature time
      series data from the climate simulations were used as input to the DORMPHOT model
      to simulate future budburst timing. The results showed an advancing trend in the
      timing of birch budburst over most regions in Ireland up to 2100. Interestingly,
      this trend appeared greater in the northeast of the country than in the
      southwest, where budburst is currently relatively early. These results could have
      implications for future forest planning, species distribution modeling, and the
      birch allergy season. 

PMID- 24037344
TI  - Lentiviral delivery of a vesicular glutamate transporter 1 (VGLUT1)-targeting
      short hairpin RNA vector into the mouse hippocampus impairs cognition.
AB  - Glutamate is the principle excitatory neurotransmitter in the mammalian brain,
      and dysregulation of glutamatergic neurotransmission is implicated in the
      pathophysiology of several psychiatric and neurological diseases. This study
      utilized novel lentiviral short hairpin RNA (shRNA) vectors to target expression
      of the vesicular glutamate transporter 1 (VGLUT1) following injection into the
      dorsal hippocampus of adult mice, as partial reductions in VGLUT1 expression
      should attenuate glutamatergic signaling and similar reductions have been
      reported in schizophrenia. The VGLUT1-targeting vector attenuated tonic glutamate
      release in the dorsal hippocampus without affecting GABA, and selectively
      impaired novel object discrimination (NOD) and retention (but not acquisition) in
      the Morris water maze, without influencing contextual fear-motivated learning or
      causing any adverse locomotor or central immune effects. This pattern of
      cognitive impairment is consistent with the accumulating evidence for functional
      differentiation along the dorsoventral axis of the hippocampus, and supports the
      involvement of dorsal hippocampal glutamatergic neurotransmission in both spatial
      and nonspatial memory. Future use of this nonpharmacological VGLUT1 knockdown
      mouse model could improve our understanding of glutamatergic neurobiology and aid
      assessment of novel therapies for cognitive deficits such as those seen in
      schizophrenia. 

PMID- 24037346
TI  - Clinical significance of serum soluble interleukin-2 receptor-alpha in extranodal
      natural killer/T-cell lymphoma (ENKTL): a predictive biomarker for treatment
      efficacy and valuable prognostic factor.
AB  - Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is an aggressive
      disease, and no standard treatment and validated prognostic model were
      established. Serum sIL-2Ralpha levels were measured in 94 ENKTL patients to
      evaluate its relationship with clinical features, treatment response, and
      prognosis. Serum sIL-2Ralpha level was 2964 +/- 1613.6 ng/L in ENKTL patients,
      higher than in normal healthy controls (p < 0.05). Using median level (2508.5
      ng/L) as cutoff, patients were divided into higher- and lower-level group (N = 47
      for each). The complete remission and overall remission rate were significantly
      higher in lower-level group (p < 0.05). After a median follow-up time of 22.0
      months, 2-year overall survival and progression-free survival rates were 60.0 and
      53.0 %, respectively. Lower sIL-2Ralpha level significantly correlated with
      better progression-free survival (PFS) and overall survival (OS) (p = 0.001 and
      0.002, respectively). IPI score and treatment responses after 2 cycles of
      chemotherapy significantly correlated with PFS and OS (p < 0.05). In a
      multivariate Cox regression model that included IPI score, treatment responses,
      and sIL-2Ralpha level, all three parameters were independent prognostic factors
      for OS (p = 0.043, 0.001, and 0.025, respectively), and the last two parameters
      were also independent factors for PFS (p = 0.005 and 0.005, respectively).
      Elevated serum sIL-2Ralpha level was related to poor responses to treatments and
      can be used as a valuable biomarker for disease activity. Moreover, serum sIL
      2Ralpha was an independent prognostic factor for both OS and PFS. These results
      need to be validated in prospective trials and may support the incorporation of
      anti-CD25 targeted therapy into the treatment realm of ENKTL.

PMID- 24037347
TI  - A metric for the stiffness of calcified aortic valves using a combined
      computational and experimental approach.
AB  - Calcific aortic valve disease is the most common heart valve disease. It is
      associated with a significant increase in cardiovascular morbidity and mortality
      and independently increases the cardiovascular risk. It is then important to
      develop parameters that can estimate the stiffness of the valve. Such parameters
      may contribute to early detection of the disease or track its progression and
      optimize the timing for therapy. In this study, we introduce a metric
      representing the stiffness of the native aortic calcified valve over a wide range
      of stenosis severities. Our approach is based on three-dimensional structural
      finite-element simulations and in vitro measurements. The proposed method is
      developed first in a pulse duplicator; its clinical applicability is then
      evaluated in three patients with severe aortic stenosis. Our results indicate
      that the value of the proposed metric varies considerably between healthy valves
      and valves with very severe aortic stenosis, from 0.001 to 7.38 MPa,
      respectively. The method introduced in this study could give useful information
      regarding the stiffness of the valve leaflets with potential application to the
      evaluation of aortic sclerosis and aortic stenosis.

PMID- 24037348
TI  - Effect of pore size on the performance of immobilised enzymes.
AB  - Porous materials are widely employed as supports in the immobilisation of
      enzymes. Traditionally macroporous materials with pore diameters >50 nm were
      believed to be the most suitable support material, ensuring no spatial
      restrictions upon enzyme molecules entering such large pores. In recent years
      however, there has been growing emphasis in the use of mesoporous supports with
      pore diameters ranging between 2 and 50 nm. It is thought this smaller pore range
      may offer enhanced conformational stability to immobilised enzymes while not
      being so small as to restrict enzyme access. Despite their increasing popularity,
      many argue that mesoporous materials have not yet proven superior to traditional
      macroporous supports for enzyme immobilisation. Through the design and
      application of a unique confidence rating system we were able to accurately
      compare data and establish trends between pore characteristics and protein
      loading. By analysing published data (182 experiments in total) and extracting
      pore characteristics and protein loading values, we have described three
      categories of pore diameters in which correlations between pore characteristics
      and protein loading are noted. With pore diameters less than 10 nm we see a
      general decrease in protein loading as the enzymes find physical restrictions in
      accessing the high surface offered in this pore diameter range. At pore sizes
      greater than 100 nm, protein loading generally decreases due to a concomitant
      reduction in available surface area. In the pore range of 10-100 nm there it is
      expected to see a decrease in protein loading level with increasing pore
      diameter. In fact protein loading in this range remains largely constant,
      suggesting some degree of protein-protein interaction blocking pores and
      restricting access to the increasing surface area available at decreasing pore
      diameters. No trends were established between pore characteristics and retention
      of activity. 

PMID- 24037349
TI  - Differences between h-index measures from different bibliographic sources and
      search engines.
AB  - OBJECTIVE: To analyze the use of the h-index as a measure of the bibliometric
      impact of Brazilian researchers' scientific publications. METHODS: The scientific
      production of Brazilian CNPq 1-A researchers in the areas of public health,
      immunology and medicine were compared. The mean h-index of the groups of
      researchers in each area were estimated and nonparametric Kruskal Wallis test and
      multiple comparisons Behrens-Fisher test were used to compare the differences.
      RESULTS: The h-index means were higher in the area of Immunology than in Public
      Health and Medicine when the Web of Science base was used. However, this
      difference disappears when the comparison is made using Scopus or Google Scholar.
      CONCLUSIONS: The emergence of Google Scholar brings a new level to discussions on
      the measure of the bibliometric impact of scientific publications. Areas with
      strong professional components, in which knowledge is produced and must also be
      published in the native language, vis-a-vis its dissemination to the
      international community, necessarily have a standard of scientific publications
      and citations different from areas exclusively or predominantly academic and they
      are best captured by Google Scholar.

PMID- 24037350
TI  - Aerosols from biomass burning and respiratory diseases in children, Manaus,
      Northern Brazil.
AB  - OBJECTIVE: To investigate the effects of fine particulate matter emitted through
      biomass burning on hospitalizations for respiratory diseases in children living
      in Manaus, Northern Brazil. METHODS: Descriptive study with ecologic time series
      design carried out in Manaus from 2002 to 2009. Hospital admission data were
      obtained from the Unified Health System database. PM2.5 levels were estimated
      using aerosol remote sensing through the measurement of aerosol optical depth at
      a wavelength of 550 nm. Statistical methods were used in the data analysis, with
      Pearson correlation and multiple linear regression between variables, with a 95%
      confidence interval. RESULTS: The region of Manaus showed low PM2.5
      concentrations when compared to the Southern Amazonian region. Between August and
      November (dry period in the region), was when the highest mean levels of PM2.5,
      estimated between 18 to 23 ug/m3, and the largest number of fires were observed.
      For the rainy season, an average of 12 ug/m3, 66% lower than the dry season
      measurements (20.6 ug/m3) was observed. The highest rates of hospitalization were
      observed during the rainy season and April was the month with the highest levels
      at 2.51/1,000 children. A positive association between hospital admissions and
      relative humidity (R = 0.126; p-value = 0.005) was observed, while the
      association between admissions and PM2.5 was negative and statistically
      significant (R = -0.168; p-value = 0.003). The R 2 of the final model
      (Hospitalizations = 2.19*Humidity - 1.60*PM2.5 - 0.23*Precipitation) explained
      84% of hospitalizations due to respiratory disease in children living in Manaus,
      considering the independent variables statistically significant (humidity, PM2.5,
      and precipitation). CONCLUSIONS: Hospital admissions for respiratory diseases in
      children in Manaus, were more related to weather conditions and in particular
      relative humidity, than to exposure to aerosols emitted by biomass burning in the
      Amazonian region.

PMID- 24037351
TI  - Vitamin A deficiency and associated factors in children in urban areas.
AB  - OBJECTIVE: To estimate the prevalence of vitamin A deficiency and its associated
      factors in children. METHODS: A cross-sectional population-based study, involving
      1,211 children of both sexes, aged between six and 59 months old, was carried out
      in the urban zone of 9 cities in the state of Paraiba, Northeastern Brazil.
      Vitamin A status was assessed by serum retinol levels (high performance liquid
      chromatography - HPLC) and subclinical infection was assessed by C-reactive
      protein concentrations. Socioeconomic, demographic and sanitation conditions, as
      well as vitamin A supplement intake, were also evaluated. Children with serum
      retinol concentrations RESULTS: The prevalence of vitamin A deficiency was 21.8%
      (95%CI 19.6;24.2), showing an association with subclinical infection and lack of
      indoor plumbing. The prevalence of vitamin A deficiency was 21.8% (95%CI
      19.6;24.2). After adjustment, vitamin A deficiency was found to be linked with
      subclinical infection and lack of indoor plumbing. Vitamin A deficiency was four
      times higher (CI95% 1.49;10.16) in children with subclinical infection whose
      homes were without indoor plumbing, compared to children who were not infected
      and with indoor plumbing in their homes. CONCLUSIONS: Despite activities aimed at
      the prevention and control of vitamin A deficiency, hypovitaminosis A, remains a
      public health concern among children under five.

PMID- 24037352
TI  - Evaluation of project promoting health in adolescents.
AB  - OBJECTIVE: Evaluate a program promoting exercise and healthy eating among
      adolescents. METHODS: This was a cross-sectional study of 911 adolescents aged 13
      to 18 years old in public schools in Goiania, Midwestern Brazil, 2010. The
      participants were divided into two groups: intervention (schools taking part in
      the Healthy Living, project) and control. The following were deemed to be
      exercise: displacement, physical education classes in school, physical activity
      outside school, and leisure-time physical activity. Pupils who totaled 300 or
      more minutes per week were defined as active. Consuming protective foods five or
      more days a week was classified as adequate intake. Statistical analyses made
      using the Chi-square test. RESULTS: Most adolescents were identified as inactive
      or insufficiently active, 65.7% in the Intervention Group and 65.2% Control
      Group, showing no significant differences between groups, and with higher
      prevalence among girls. Slightly more than half of adolescents consumed health
      protective foods 5 or more days a week, 56.6% in the Intervention Group and 50.4%
      in the Control Group (p = 0.373). CONCLUSIONS: There were no differences between
      schools in the Intervention Group and Control Group with regard to food choices
      and physical activity. This indicates that the Healthy Living project needs to be
      reevaluated to improve the effectiveness in achieving its objectives.

PMID- 24037353
TI  - Prevalence of falls among frail elderly adults.
AB  - OBJECTIVE: To measure the prevalence in frail elderly people, their consequences
      and associated demographic factors. METHODS: This was an epidemiological and
      cross-sectional study with a probabilistic sample composed of 240 elderly people
      (>= 60 years) living in Ribeirao Preto, Sao Paulo state. Data were collected
      between November 2010 and February 2011, through a questionnaire that included
      socio-demographic data, fall assessment and the Edmonton Frailty Scale. Uni
      variate and bivariate analyses were carried out. RESULTS: The mean age was 73.5
      (+/- 8.4), with higher ages among women; 25% of the interviewees were aged 80 or
      older; 11.3% presented moderate frailty and 9.6% severe frailty. The prevalence
      of falls in frail elderly participants corresponded to 38.6%; higher levels were
      found among women and younger subjects (60 to 79 years old); 26.8% were victims
      of 1 to 2 falls, 27.1% of which occurred in the bedroom, 84.7% fell from their
      own height, 55.9% lost their balance, 54.2% suffered scratches and 78% were
      afraid of suffering a new fall. Higher fall prevalence levels were found in frail
      elderly 1,973 (1,094-3,556) compared to non-frail. CONCLUSIONS: We highlight the
      importance of addressing the health of frail elderly people, especially regarding
      the risk of falls, as well as of increasing investment in prevention strategies
      of these syndromes and in the formation of train like a virgin ed human resources
      to better care for this population.

PMID- 24037354
TI  - Age-period-cohort effect on mortality from cervical cancer.
AB  - OBJECTIVE: To estimate the effect of age, period and birth cohort on mortality
      from cancer of the cervix. METHODS: Mortality data for cervical cancer in women
      aged over 30, between 1980 and 2009, for the municipalities of Rio de Janeiro and
      Sao Paulo, Southeastern Brazil,were extracted from the Mortality Information
      System. The estimated annual percentage change was calculated for the periods
      1980-1994 and 1995-2009. Age, period and cohort effects were assessed employing
      the Poisson regression model, using estimated functions, deviations, curvatures
      and drift through the library Epi statistical program R version 2.7.2. RESULTS:
      The average mortality rate per 100,000 women for the period in Rio de Janeiro was
      15.90 and 15.87 in Sao Paulo. There was a significant reduction in mortality from
      cervical cancer in the two periods (1980-1994 and 1995-2009) in both Rio de
      Janeiro, -1.20% (95%CI -2.20;-0.09) -1.46% (95%CI -2.30;0.61) and in Sao Paulo, 
      2.58% (95%CI -3.41;1.76) and -3.30% (95%CI -4.30;2.29). The analysis of effects
      of curvature indicated reduction in deaths in successive cohorts (RR < 1 in women
      born after the 1960s). There was marked reduction in relative risk (RR) from the
      2000s onwards. CONCLUSIONS: The study showed that, in the time period analyzed,
      the period had an effect on the reduction in mortality rates for cervical cancer,
      bearing in mind that there was a protective effect (RR < 1) from the year 2000
      onwards and in women born after the 1960s.

PMID- 24037355
TI  - External causes and maternal mortality: proposal for classification.
AB  - OBJECTIVE: To analyze deaths from external causes and undefined causes in women
      of childbearing age occurring during pregnancy and early postpartum. METHODS: The
      deaths of 399 women of childbearing age, resident in Recife, Northeastern Brazil,
      in the period 2004 to 2006, were studied. The survey utilized the Reproductive
      Age Mortality Survey method and a set of standardized questionnaires. Data
      sources included reports from the Institute of Legal Medicine, hospital and
      Family Health Strategy records and interviews with relatives of the deceased
      women. External causes of death during pregnancy were classified according to the
      circumstance of death, using the O93 code (ICD) and maternal mortality ratios
      before and after the classification were calculated. RESULTS: Eighteen deaths
      during pregnancy were identified. The majority were aged between 20 and 29, had
      between 4 and 7 years of schooling, were black and single parents. Fifteen deaths
      were classified using the O93 code as pregnancy related death (13 for homicide -
      code 93.7; 2 by suicide - code 93.6) and three were classified as indirect
      obstetric maternal deaths (one homicide - code 93.7 and two by suicide - code
      93.6). There was an average increment of 35% in the RMM after classification.
      CONCLUSIONS: Deaths from undefined causes in and in early postpartumdid not occur
      by chance and their exclusion from the calculations of maternal mortality
      indicators only increases levels of underreporting.

PMID- 24037356
TI  - Brazilian adaptation of the questionnaire to assess adherence to treatment for
      arterial hypertension.
AB  - OBJECTIVE: To describe the cross-cultural adaptation of the questionnaire
      evaluating adhesion to treatment for arterial hypertension from its original
      Spanish version to a Portuguese version, to be applied in Brazil. METHODS: In
      order to establish conceptual, semantic and operational equivalents of the items,
      two independent translations to Portuguese, and two back-translations into
      Spanish were performed. The translations and back-translations were assessed for
      changes in referential and general meanings. The synthesis of the translations
      was applied in pre-tests with patients with arterial hypertension and/or
      diabetes, which were important to identify different problems and confirm earlier
      decisions. RESULTS: In general, the second translation and back translation were
      evaluated more positively because the translation process did not affect the
      meanings in five of the twelve items of the questionnaire. Operational changes
      were made and a vignette with response options and an example included in the
      instrument facilitated application in interviews. CONCLUSIONS: The results
      obtained in the process of evaluating the items' conceptual, semantic and
      operational equivalence allowed the construction of a Portuguese version of the
      MBG questionnaire to assess adherence to treatment which can be applied in the
      Brazilian context.

PMID- 24037357
TI  - Low prevalence of hypertension with pharmacological treatments and associated
      factors.
AB  - OBJECTIVE: To assess the determinants of the lack of pharmacological treatment
      for hypertension. METHODS: In 2005, 3,323 Mozambicans aged 25-64 years old were
      evaluated. Blood pressure, weight, height and smoking status were assessed
      following the Stepwise Approach to Chronic Disease Risk Factor Surveillance.
      Hypertensives (systolic blood pressure >= 140 mmHg and/or diastolic blood
      pressure >= 90 mmHg and/or antihypertensive drug therapy) were evaluated for
      awareness of their condition, pharmacological and non-pharmacological management,
      as well as use of herbal or traditional remedies. Prevalence ratios (PR) were
      calculated, adjusted for sociodemographic characteristics, cardiovascular risk
      factors and non-pharmacological treatment. RESULTS: Most of the hypertensive
      subjects (92.3%), and nearly half of those aware of their condition were not
      treated pharmacologically. Among the aware, the prevalence of untreated
      hypertension was higher in men {PR = 1.61; 95% confidence interval (95%CI
      1.10;2.36)} and was lower in subjects under non-pharmacological treatment (PR =
      0.58; 95%CI 0.42;0.79); there was no significant association with traditional
      treatments (PR = 0.75; 95%CI 0.44;1.26). CONCLUSIONS: The lack of pharmacological
      treatment for hypertension was more frequent in men, and was not influenced by
      the presence of other cardiovascular risk factors; it could not be explained by
      the use of alternative treatments as herbal/traditional medicines or non
      pharmacological management. It is important to understand the reasons behind the
      lack of management of diagnosed hypertension and to implement appropriate
      corrective actions to reduce the gap in the access to healthcare between
      developed and developing countries.

PMID- 24037358
TI  - Survey of hearing disorders in an urban population in Rondonia, Northern Brazil.
AB  - OBJECTIVE: To identify the prevalence of hearing loss for the population in the
      urban area. METHODS: A cross-sectional household survey based on the World Health
      Organization Ear and Hearing Disorders Survey Protocol was conducted in 298
      households in the urban area of Monte Negro, Rondonia, Northern Brazil, from 2005
      to 2007. Ear examinations, behavioral audiometry and pure tone audiometry were
      conducted on 577 individuals. RESULTS: The results showed that 3.8% (95%CI
      2.17;5.45) of population were classified in the disabling hearing impairment
      category. The prevalence of moderate hearing impairment was 3.4%; severe
      impairment was 0.4%; and profound hearing impairment was not found. CONCLUSIONS:
      The impairing hearing loss prevalence found in this study is within of the
      international prevalence for this level of hearing loss and smaller than observed
      in a previous study in the South region of Brazil.

PMID- 24037359
TI  - Telephone survey: post-stratification adjustments to compensate non-coverage bias
      in city of Rio Branco, Northern Brazil.
AB  - OBJECTIVE: To evaluate the effects of using post-stratification weight to correct
      the bias due to low coverage of households with telephones. METHODS: A Comparison
      was made of results collected by the Household Survey with those of the VIGITEL
      (Telephone Survey to Monitor Risk and Protective Factors for Chronic Diseases) in
      Rio Branco, Northern Brazil, in 2007 whose coverage was 40% of landline phones.
      The potential bias in the VIGITEL survey was expressed by the difference between
      the rates of prevalence of the VIGITEL and Household Survey, calculated as the
      square root mean square error (MSE) as a measure of the accuracy of the estimate.
      RESULTS: The weighting procedure of VIGITEL corrected potential bias in the
      prevalence of consumption of fruit and vegetables, meat with visible fat,
      smoking, bad self-assessment of health status and morbidity of cholesterol or
      triglycerides. In the prevalence of physical activity in leisure time and
      morbidity of asthma, bronchial asthma, chronic bronchitis or emphysema, the
      procedure adopted by VIGITEL did not reduce the potential bias. CONCLUSIONS: in
      order to construct post-stratification weights which minimize the potential bias
      in estimates of the variables due to low coverage of households with landlines,
      it becomes necessary to use alternative methods of weighting and strategies of
      selecting external variables.

PMID- 24037360
TI  - Adaptation and content validation of the Brazilian version of the Posttraumatic
      Cognitions Inventory.
AB  - OBJECTIVE: To translate, adapt and validate the contents of the Brazilian version
      of the Posttraumatic Cognitions Inventory. METHODS: The process of translation
      and adaptation of the initial instructions and items involved five steps: (1)
      translation; (2) back translation; (3) correction and semantic adaptation; (4)
      content validation by professional experts (judges); and (5) test of final
      version through a verbal-numbered scale. As performance indicators for
      understanding, the scores of central tendency (mean) and dispersion (standard
      deviation) were calculated for each item in step 5. Satisfactory comprehension
      was defined as a mean score >= 3. RESULTS The 36 questions and the initial
      instructions were translated and adapted to create the Brazilian version of the
      Posttraumatic Cognitions Inventory. In the final stage of testing, 45 adults
      answered the items and demonstrated an adequate understanding of the instrument
      in the verbal-numbered scale (M = 4.13; dp = 0.11). CONCLUSIONS The Posttraumatic
      Cognitions Inventory is an easily understood and semantically valid instrument.
      Further studies are needed to verify and evaluate the appropriateness of its
      psychometric properties for the Brazilian population.

PMID- 24037361
TI  - Human risk assessment of benzene after a gasoline station fuel leak.
AB  - OBJECTIVE: To assess the health risk of exposure to benzene for a community
      affected by a fuel leak. METHODS: Data regarding the fuel leak accident with,
      which occurred in the Brasilia, Federal District, were obtained from the Fuel
      Distributor reports provided to the environmental authority. Information about
      the affected population (22 individuals) was obtained from focal groups of eight
      individuals. Length of exposure and water benzene concentration were estimated
      through a groundwater flow model associated with a benzene propagation model. The
      risk assessment was conducted according to the Agency for Toxic Substances and
      Disease Registry methodology. RESULTS: A high risk perception related to the
      health consequences of the accident was evident in the affected community (22
      individuals), probably due to the lack of assistance and a poor risk
      communication from government authorities and the polluting agent. The community
      had been exposed to unsafe levels of benzene (> 5 ug/L) since December 2001, five
      months before they reported the leak. The mean benzene level in drinking water
      (72.2 ug/L) was higher than that obtained by the Fuel Distributer using the Risk
      Based Corrective Action methodology (17.2 ug/L).The estimated benzene intake from
      the consumption of water and food reached a maximum of 0.0091 ug/kg bw/day (5 x
      10-7 cancer risk per 106 individuals). The level of benzene in water vapor while
      showering reached 7.5 ug/m3 for children (1 per 104 cancer risk). Total cancer
      risk ranged from 110 to 200 per 106 individuals. CONCLUSIONS: The population
      affected by the fuel leak was exposed to benzene levels that might have
      represented a health risk. Local government authorities need to develop better
      strategies to respond rapidly to these types of accidents to protect the health
      of the affected population and the environment.

PMID- 24037362
TI  - Particulate matter originating from biomass burning and respiratory.
AB  - OBJECTIVE: To analyze the effects of exposure to fine particulate matter from
      burning on hospital admissions due to respiratory diseases in children and the
      elderly. METHODS: This is an ecological time series study that took place in the
      city of Cuiaba, Mato Grosso, in Brazil's Amazon Region, in 2005. Information on
      the daily levels of fine particulate matter PM2.5 was made available by the
      Brazilian National Institute for Spatial Research. The model included variables
      related to temperature, relative humidity and adjusts for seasonality and
      calendar effects. Poisson regression with generalized additive models was used.
      RESULTS: A 10 ug/m3 increase in the level of exposure to PM2.5 was associated
      with increases of 9.1%, 9.2% and 12.1% in hospital admissions due to respiratory
      diseases in children for moving averages of 1, 2 and 5 days, respectively. For
      the dry season, the level of exposure to particulate matter was associated with
      increases of 11.4%, 21.6% and 22.0% in hospital admissions in children for moving
      averages of 1, 5 and 6 days, respectively. No significant link was noticed in the
      elderly. CONCLUSIONS: The results show the influence of PM2.5 on hospitalizations
      for respiratory disease in children under 5 in the region studied.

PMID- 24037363
TI  - [Anthropological view of the decentralization of the Mexican health system].
AB  - OBJECTIVE: To analyze organizational, political and economic changes resulting
      from the decentralization of the health system for those in Mexico without health
      insurance. METHODS: Three states, selected by considering the percentage of the
      population living in poverty, the political party in power and their stage of
      decentralization (the first was in 1984 and the second in 1997) were included.
      Interviews were conducted during 2007 with key informants from the state health
      care services, users of health care services, and community leaders. Data were
      analyzed from an anthropological and economic perspective. RESULTS:
      Decentralization occurred in a heterogeneous way in each state, with
      responsibilities being transferred from federal to state level but without
      breaking the dependence on the central-federal level. The reforms driven from the
      federal level to create a scheme based on a principle of financial subsidies and
      democratization of the health system face challenges for their political and
      organizational consolidation. CONCLUSIONS: The anthropological approach adopted
      in this analysis shows the relevance of considering organizational, economic and
      political factors as key components of the decentralization process.

PMID- 24037364
TI  - [Art, culture and care in psychosocial healthcare services].
AB  - OBJECTIVE: To analyze the process of care developed in group activities of
      culture and art in community psychosocial healthcare centres. METHODS: This study
      is part of research evaluating psychosocial health care centers in the city of
      Sao Paulo. Ethnographic reports of 126 art and cultural group activities taking
      place in 21 centers between 2007 and 2008 were analyzed. The analysis included
      statements from coordinators on the objectives of the observed activities. Based
      on theoretical psychosocial health care frameworks, content analysis was used to
      investigate the relationship between the therapeutic tools used and the
      objectives of the activities. RESULTS: Three trends of health care were
      identified: (1) strictly clinical, was predominant and characterized by
      activities carried out within the centers, with a focus on personal skills and
      group interactions; (2) psychosocial, including outdoor activities, widening the
      cultural repertoire and social circulation and; (3) residual, in the minority and
      without psychosocial benefits. CONCLUSIONS: Carrying out art and cultural
      activities which result in health care from the perspective of psychosocial
      rehabilitation depends on the health care professionals' access to cultural
      assets and creative procedures, on the recognition of these activities as part of
      the coordinated work of a team and on all those involved being considered as
      actual producers of culture.

PMID- 24037365
TI  - [Access to pediatric cancer care in Brazil: mapping origin-destination flows].
AB  - OBJECTIVE: To analyze fl ows of travel between place of residence and health care
      services by children and adolescents with cancer. METHODS: The flows of travel
      between place of residence and the health care service for children and
      adolescents receiving care in Brazil's Unifi ed Health System (SUS) were
      monitored between 2000 and 2007. The unit of analysis was the health care
      district. The geographical information system data and network methodology, by
      type of treatment received (chemotherapy and radiotherapy) and hospital
      admissions were used. RESULTS: The SUS made 465,289 authorizations for
      chemotherapy, 29,151 for radiotherapy and 383,568 for hospital admissions for the
      treatment of children and adolescents with a diagnosis of cancer. The dominant fl
      ow formed 48 networks for chemotherapy, 53 for radiotherapy and 112 for hospital
      admissions. Most of the volume of treatment occurred in the health districts of
      Brazil's 12 largest cities (with strong links between them and each having an
      extensive area of direct infl uence accompanying the structure of the Brazilian
      urban system. CONCLUSIONS: Identifying the networks formed by utilization of SUS
      facilities providing care for children and adolescents with cancer shows that
      overall most patients are covered by the existing networks. However, about 10% of
      travel occurs outside the dominant structure, indicating the need for alternative
      regionalization. These results show the importance of planning the distribution
      of services to meet the population's needs.

PMID- 24037366
TI  - [Preventable infant mortality and barriers to access to primary care in Recife,
      Northeastern Brazil].
AB  - OBJECTIVE: Analyze the factors infl uencing avoidable infant mortality from the
      perspective of the protagonists involved. METHODS: Qualitative study with a
      critical-constructivist approach, examining children's access to health care and
      avoiding preventable infant mortality through health care campaigns and services
      in Health District I of Recife, Northeastern Brazil, between February 2007 and
      February 2008. The theoretical sample was designed in two stages: I) institutions
      providing health services to children; II) interviewees: managers (11);
      professionals from the Family Health Strategy and Programme of Community Health
      Workers (48); and from outpatient clinics (12); mothers (20), with sample size
      defi ned by "saturation of the speeches". Data was collected using individual
      semistructured interviews and case studies of avoidable infant death. Thematic
      content analysis was used, generating mixed categories (emerging and scripted).
      RESULTS: There were perceived to be confl icting positions between different
      stakeholder groups refl ecting their role in the care network. All institutional
      participants related infant deaths to the absence/poor dissemination of child
      health policies and inter-sectoral actions; professionals and mothers highlighted
      diffi culties in accessing health care due to insuffi cient global resources,
      especially the lack of doctors in Family Health Strategy, shifting health care to
      nurses. Lack of doctors, acute diseases rejection, and dehumanized and/or poor
      technical quality care were the main factors which the mothers related to deaths.
      Family Health Strategy participants from the Programme of Community Health
      Workers and mothers identifi ed the condition of social exclusion and maternal
      neglect with deaths, but the case study of death revealed the association with
      lower quality of care offered. CONCLUSIONS: Numerous barriers to access indicate
      insuffi cient the Brazilian Unifi ed Health System implementation and lack of
      resolution of the main access route, the Family Health Strategy. The results
      indicate the need for improvement of structural and organizational factors of
      supply, with emphasis on mechanisms to stimulate the recruitment of doctors for
      the Family Health Strategy professional training of all staff consistent with the
      model of care to comply with health care policies for children and avoiding
      preventable infant mortality.

PMID- 24037367
TI  - [Public spending on drugs for the treatment of osteoporosis in post-menopause].
AB  - OBJECTIVE: To analyze expenditure on treatment for postmenopausal osteoporosis
      and associated factors on mean per capita expenditure. METHODS: A probabilistic
      deterministic linkage between the database of Authorizations for Highly Complex
      Procedures and the mortality information system was constructed, resulting in a
      historical cohort of patients using high-cost medications for the treatment of
      postmenopausal osteoporosis, between 2000-2006. Mean monthly spending on
      medicines was stratified by age group and described according to demographic and
      clinical characteristics and the type of drug used. A linear regression model was
      used to assess the impact of demographic and clinical characteristics on per
      capita mean monthly expenditure on medicines. RESULTS: We identified 72,265 women
      who received drugs for the treatment of postmenopausal osteoporosis. The average
      monthly expenditure per capita in the first year of treatment was $ 54.02 (sd $
      86.72). The population was predominantly composed of women aged 60-69 years old,
      who had started treatment in 2000, resident in the Southeast of Brazil, who had
      previously suffered osteoporotic fractures, and Alendronate sodium was the drug
      most commonly used at baseline. For most of the patients, the same active
      ingredient remained in use throughout the treatment period. During the program,
      6,429 deaths were identified among participants. More than a third of women
      remained in treatment for up to 12 months. Raloxifen and calcitonin were the
      therapeutic alternatives with the greatest impact on the average monthly
      expenditure on medicine using alendronate sodium as a reference standard.
      CONCLUSIONS: Due to the high impact of the type of drug used on expenditure on
      medication, it is recommended that criteria for prescribing and dispensing be
      established by prioritizing those with lower costs and greater effectiveness in
      order to optimize the process of pharmaceutical care and provide the population
      with a greater number of pharmaceutical units.

PMID- 24037368
TI  - Professional and community satisfaction with the Brazilian family health
      strategy.
AB  - OBJECTIVE: To analyze the strengths and limitations of the Family Health Strategy
      from the perspective of health care professionals and the community. METHODS:
      Between June-August 2009, in the city of Vespasiano, Minas Gerais State,
      Southeastern Brazil, a questionnaire was used to evaluate the Family Health
      Strategy (ESF) with 77 healthcare professionals and 293 caregivers of children
      under five. Health care professional training, community access to health care,
      communication with patients and delivery of health education and pediatric care
      were the main points of interest in the evaluation. Logistic regression analysis
      was used to obtain odds ratios and 95% confidence intervals as well as to assess
      the statistical significance of the variables studied. RESULTS: The majority of
      health care professionals reported their program training was insufficient in
      quantity, content and method of delivery. Caregivers and professionals identified
      similar weaknesses (services not accessible to the community, lack of healthcare
      professionals, poor training for professionals) and strengths (community health
      worker-patient communications, provision of educational information, and
      pediatric care). Recommendations for improvement included: more doctors and
      specialists, more and better training, and scheduling improvements. Caregiver
      satisfaction with the ESF was found to be related to perceived benefits such as
      community health agent household visits (OR 5.8, 95%CI 2.8;12.1), good
      professional-patient relationships (OR 4.8, 95%CI 2.5;9.3), and family-focused
      health (OR 4.1, 95%CI 1.6;10.2); and perceived problems such as lack of personnel
      (OR 0.3, 95%CI 0.2;0.6), difficulty with access (OR 0.2, 95%CI 0.1;0.4), and poor
      quality of care (OR 0.3, 95%CI 0.1;0.6). Overall, 62% of caregivers reported
      being generally satisfied with the ESF services. CONCLUSIONS: Identifying the
      limitations and strengths of the Family Health Strategy from the healthcare
      professional and caregiver perspective may serve to advance primary community
      healthcare in Brazil.

PMID- 24037369
TI  - Association between Schistosomiasis mansoni and hepatitis C: systematic review.
AB  - OBJECTIVE: To perform a systematic review of the prevalence of the HCV/ S.
      mansoni co-infection and associated factors in Schistosoma mansoni -infected
      populations. METHODS: The bibliographic search was carried out using the Medline,
      Lilacs, SciELO, Cochrane Library and Ibecs databases. The criteria for the
      studies' selection and the extraction data were based on systematic review
      methods. Forty five studies were found, with nine being excluded in a first
      screening. Thirteen articles were used for data extraction. RESULTS: The HCV
      infection rates in schistosomiasis populations range from 1% in Ethiopia to 50%
      in Egypt. Several studies had poorly defined methodologies, even in areas
      characterized by an association between hepatitis C and schistosomiasis, such as
      Brazil and Egypt, which meant conclusions were inconsistent. HCV infection rates
      in schistosomotic populations were heterogeneous and risk factors for acquiring
      the virus varied widely. CONCLUSIONS: Despite the limitations, this review may
      help to identify regions with higher rates of hepatitis C and schistosomiasis
      association. However, more studies are necessary for the development of public
      health policies on prevention and control of both diseases.

PMID- 24037370
TI  - [Moral dilemmas and health practices].
AB  - The emergence of moral dilemmas in health care practices, in view of the rapid
      demographic transition in developing countries, and skyrocketing public health
      care costs, is discussed. The focus is on two aspects of health care that have
      occupied an important place in the generation of these dilemmas. On the one hand,
      the tension between commercial strategies involving the health products market
      and the expansion of access to them and, on the other, the growth of techno
      sciences in health care practices. In conclusion, the importance of the
      political, social and juridical arbitration on the ethical codifi cation of those
      dilemmas and the role of a Democratic State of Law in that arbitration is
      discussed. 

PMID- 24037371
TI  - Tonic stimulation of the pharyngeal mucosa causes pain and a reversible increase
      of inflammatory mediators.
AB  - OBJECTIVE AND DESIGN: To develop a model of the inflammatory component of non
      infectious sore throat using tonic stimulation and quantification of inflammatory
      mediators in pharyngeal lavage fluid. MATERIAL OR SUBJECTS: Forty-five healthy
      volunteers. TREATMENT: Cold dry air. METHOD: Tonic stimulation of the pharynx was
      achieved using a constant stream of cold dry air to the back of the throat.
      Following optimization of stimulation conditions (phase 1), pharyngeal pain,
      irritation, and swallowing discomfort were assessed using visual analog scales,
      and the concentration of inflammatory markers were measured in pharyngeal lavage
      fluid (phase 2). RESULTS: Optimum conditions for tonic pharyngeal stimulation
      were cold dry air at 12  degrees C, relative humidity 20 %, at a flow rate of 12
      L/min for 15 min. Analysis of pharyngeal lavage fluid collected 5 min after
      stimulation showed significant increases in prostaglandin E2 (P = 0.018),
      thromboxane B2 (P < 0.001), and substance P (P < 0.001), but no increase in
      peptidoleukotriene. When the stimulus was removed, the level of inflammatory
      markers in pharyngeal lavage fluid returned to baseline by 30 min post
      stimulation. These objective measures mirrored subjective pain ratings.
      CONCLUSIONS: Tonic stimulation of the pharyngeal mucosa with cold dry air causes
      pain and an increase of inflammatory mediators which are reversible.

PMID- 24037372
TI  - A halocin-H4 mutant Haloferax mediterranei strain retains the ability to inhibit
      growth of other halophilic archaea.
AB  - Many members of the Halobacteriaceae were found to produce halocins, molecules
      that inhibit the growth of other halophilic archaea. Halocin H4 that is produced
      by Haloferax mediterranei and inhibits the growth of Halobacterium salinarum is
      one of the best studied halocins to date. The gene encoding this halocin had been
      previously identified as halH4, located on one of Hfx. mediterranei megaplasmids.
      We generated a mutant of the halH4 gene and examined the killing ability of the
      Haloferax mediterranei halH4 mutant with respect to both Halobacterium salinarum
      and Haloferax volcanii. We showed that both wild-type Hfx. mediterranei and the
      halH4 mutant strain efficiently inhibited the growth of both species, indicating
      halocin redundancy. Surprisingly, the halH4 deletion mutant exhibited faster
      growth in standard medium than the wild type, and is likely to have a better
      response to several nucleotides, which could explain this phenotype. 

PMID- 24037374
TI  - A chiral indolocarbazole foldamer displaying strong circular dichroism responsive
      to anion binding.
AB  - A chiral foldamer that consists of three indolocarbazoles and chiral amide
      residues folds into a helical conformation with the orientation bias, thus
      displaying characteristic CD signals. The X-ray crystal structure of its chloride
      complex was found to be a left-handed (M-) helix which stacks to give one
      dimensional columnar arrays. 

PMID- 24037373
TI  - Systematic study of subcellular localization of Arabidopsis PPR proteins confirms
      a massive targeting to organelles.
AB  - Four hundred and fifty-eight genes coding for PentatricoPeptide Repeat (PPR)
      proteins are annotated in the Arabidopsis thaliana genome. Over the past 10
      years, numerous reports have shown that many of these proteins function in
      organelles to target specific transcripts and are involved in post
      transcriptional regulation. Therefore, they are thought to be important players
      in the coordination between nuclear and organelle genome expression. Only four of
      these proteins have been described to be addressed outside organelles, indicating
      that some PPRs could function in post-transcriptional regulations of nuclear
      genes. In this work, we updated and improved our current knowledge on the
      localization of PPR proteins of Arabidopsis within the plant cell. We
      particularly investigated the subcellular localization of 166 PPR proteins whose
      targeting predictions were ambiguous, using a combination of high-throughput
      cloning and microscopy. Through systematic localization experiments and data
      integration, we confirmed that PPR proteins are largely targeted to organelles
      and showed that dual targeting to both the mitochondria and plastid occurs more
      frequently than expected. These results allow us to speculate that dual-targeted
      PPR proteins could be important for the fine coordination of gene expressions in
      both organelles. 

PMID- 24037375
TI  - Key role of symbiotic dinitrogen fixation in tropical forest secondary
      succession.
AB  - Forests contribute a significant portion of the land carbon sink, but their
      ability to sequester CO2 may be constrained by nitrogen, a major plant-limiting
      nutrient. Many tropical forests possess tree species capable of fixing
      atmospheric dinitrogen (N2), but it is unclear whether this functional group can
      supply the nitrogen needed as forests recover from disturbance or previous land
      use, or expand in response to rising CO2 (refs 6, 8). Here we identify a powerful
      feedback mechanism in which N2 fixation can overcome ecosystem-scale deficiencies
      in nitrogen that emerge during periods of rapid biomass accumulation in tropical
      forests. Over a 300-year chronosequence in Panama, N2-fixing tree species
      accumulated carbon up to nine times faster per individual than their non-fixing
      neighbours (greatest difference in youngest forests), and showed species-specific
      differences in the amount and timing of fixation. As a result of fast growth and
      high fixation, fixers provided a large fraction of the nitrogen needed to support
      net forest growth (50,000 kg carbon per hectare) in the first 12 years. A key
      element of ecosystem functional diversity was ensured by the presence of
      different N2-fixing tree species across the entire forest age sequence. These
      findings show that symbiotic N2 fixation can have a central role in nitrogen
      cycling during tropical forest stand development, with potentially important
      implications for the ability of tropical forests to sequester CO2. 

PMID- 24037376
TI  - Type 2 innate lymphoid cells control eosinophil homeostasis.
AB  - Eosinophils are specialized myeloid cells associated with allergy and helminth
      infections. Blood eosinophils demonstrate circadian cycling, as described over 80
      years ago, and are abundant in the healthy gastrointestinal tract. Although a
      cytokine, interleukin (IL)-5, and chemokines such as eotaxins mediate eosinophil
      development and survival, and tissue recruitment, respectively, the processes
      underlying the basal regulation of these signals remain unknown. Here we show
      that serum IL-5 levels are maintained by long-lived type 2 innate lymphoid cells
      (ILC2) resident in peripheral tissues. ILC2 cells secrete IL-5 constitutively and
      are induced to co-express IL-13 during type 2 inflammation, resulting in
      localized eotaxin production and eosinophil accumulation. In the small intestine
      where eosinophils and eotaxin are constitutive, ILC2 cells co-express IL-5 and IL
      13; this co-expression is enhanced after caloric intake. The circadian
      synchronizer vasoactive intestinal peptide also stimulates ILC2 cells through the
      VPAC2 receptor to release IL-5, linking eosinophil levels with metabolic cycling.
      Tissue ILC2 cells regulate basal eosinophilopoiesis and tissue eosinophil
      accumulation through constitutive and stimulated cytokine expression, and this
      dissociated regulation can be tuned by nutrient intake and central circadian
      rhythms. 

PMID- 24037377
TI  - Calving fluxes and basal melt rates of Antarctic ice shelves.
AB  - Iceberg calving has been assumed to be the dominant cause of mass loss for the
      Antarctic ice sheet, with previous estimates of the calving flux exceeding 2,000
      gigatonnes per year. More recently, the importance of melting by the ocean has
      been demonstrated close to the grounding line and near the calving front. So far,
      however, no study has reliably quantified the calving flux and the basal mass
      balance (the balance between accretion and ablation at the ice-shelf base) for
      the whole of Antarctica. The distribution of fresh water in the Southern Ocean
      and its partitioning between the liquid and solid phases is therefore poorly
      constrained. Here we estimate the mass balance components for all ice shelves in
      Antarctica, using satellite measurements of calving flux and grounding-line flux,
      modelled ice-shelf snow accumulation rates and a regional scaling that accounts
      for unsurveyed areas. We obtain a total calving flux of 1,321 +/- 144 gigatonnes
      per year and a total basal mass balance of -1,454 +/- 174 gigatonnes per year.
      This means that about half of the ice-sheet surface mass gain is lost through
      oceanic erosion before reaching the ice front, and the calving flux is about 34
      per cent less than previous estimates derived from iceberg tracking. In addition,
      the fraction of mass loss due to basal processes varies from about 10 to 90 per
      cent between ice shelves. We find a significant positive correlation between
      basal mass loss and surface elevation change for ice shelves experiencing surface
      lowering and enhanced discharge. We suggest that basal mass loss is a valuable
      metric for predicting future ice-shelf vulnerability to oceanic forcing. 

PMID- 24037380
TI  - Biological and analytical variation of clinical biomarker testing: implications
      for biomarker-guided therapy.
AB  - Testing for serum-based biomarkers are essential for diagnosis, risk
      stratification, and management of patients with cardiovascular disease. All
      biomarker assays have inherent analytical variability (coefficient of variance
      CVA), ranging from 5-20 %. There are also variances within a subject over time
      (CVI) and between subjects (CVG). Variances are determined by experimentation
      under controlled conditions on healthy subjects. Once measured, the index of
      individuality (II), reference change value (RCV), and number of samples to
      establish a homeostatic set point can be calculated. These attributes affect how
      results of biomarker tests are interpreted in routine clinical practice such as
      cardiac troponin for acute coronary syndromes, the natriuretic peptides, galectin
      3 and sST2 for heart failure, lipids and lipoproteins for primary cardiovascular
      disease risk, and liver function tests and skeletal muscle biomarkers for
      detecting complications from statin use. 

PMID- 24037379
TI  - X-ray structure of dopamine transporter elucidates antidepressant mechanism.
AB  - Antidepressants targeting Na(+)/Cl(-)-coupled neurotransmitter uptake define a
      key therapeutic strategy to treat clinical depression and neuropathic pain.
      However, identifying the molecular interactions that underlie the pharmacological
      activity of these transport inhibitors, and thus the mechanism by which the
      inhibitors lead to increased synaptic neurotransmitter levels, has proven
      elusive. Here we present the crystal structure of the Drosophila melanogaster
      dopamine transporter at 3.0 A resolution bound to the tricyclic antidepressant
      nortriptyline. The transporter is locked in an outward-open conformation with
      nortriptyline wedged between transmembrane helices 1, 3, 6 and 8, blocking the
      transporter from binding substrate and from isomerizing to an inward-facing
      conformation. Although the overall structure of the dopamine transporter is
      similar to that of its prokaryotic relative LeuT, there are multiple
      distinctions, including a kink in transmembrane helix 12 halfway across the
      membrane bilayer, a latch-like carboxy-terminal helix that caps the cytoplasmic
      gate, and a cholesterol molecule wedged within a groove formed by transmembrane
      helices 1a, 5 and 7. Taken together, the dopamine transporter structure reveals
      the molecular basis for antidepressant action on sodium-coupled neurotransmitter
      symporters and elucidates critical elements of eukaryotic transporter structure
      and modulation by lipids, thus expanding our understanding of the mechanism and
      regulation of neurotransmitter uptake at chemical synapses. 

PMID- 24037378
TI  - Transcriptome and genome sequencing uncovers functional variation in humans.
AB  - Genome sequencing projects are discovering millions of genetic variants in
      humans, and interpretation of their functional effects is essential for
      understanding the genetic basis of variation in human traits. Here we report
      sequencing and deep analysis of messenger RNA and microRNA from lymphoblastoid
      cell lines of 462 individuals from the 1000 Genomes Project--the first uniformly
      processed high-throughput RNA-sequencing data from multiple human populations
      with high-quality genome sequences. We discover extremely widespread genetic
      variation affecting the regulation of most genes, with transcript structure and
      expression level variation being equally common but genetically largely
      independent. Our characterization of causal regulatory variation sheds light on
      the cellular mechanisms of regulatory and loss-of-function variation, and allows
      us to infer putative causal variants for dozens of disease-associated loci.
      Altogether, this study provides a deep understanding of the cellular mechanisms
      of transcriptome variation and of the landscape of functional variants in the
      human genome.

PMID- 24037381
TI  - Correction of cryptotia with upper auricular deformity: double V-y advancement
      flap and cartilage strut graft techniques.
AB  - Cryptotia is one of the most common auricular anomalies among East Asians and it
      is frequently associated with upper auricular malformation. Various surgical
      techniques have been described in the literature, such as V-Y plasty, Z-plasty,
      skin grafts, local skin flaps, and so on. Although relatively favorable results
      were obtained by these techniques, some problems remain, such as conspicuous
      scars, undercorrected or noncorrected auricular cartilage deformities, irregular
      contour, hair growth, and shallow auriculocephalic sulcus. Because both skin
      deficiency and cartilage deformities must be corrected for cryptotia with upper
      auricular deformity, the author has developed new surgical techniques, namely
      double V-Y advancement flap and cartilage strut graft techniques. These methods
      provide enough skin to the deformed areas and also good auricular contour with
      expanded upper auricular portion. 

PMID- 24037383
TI  - Third-ventricular neurocysticercosis: hydraulic maneuvers facilitating endoscopic
      resection.
AB  - BACKGROUND: Neurocysticercosis, an infection of the central nervous system with
      the larval cysts of the pork tapeworm, Taenia solium, is the most common
      parasitic disease of the central nervous system. The disease is a major global
      cause of acquired epilepsy and may also manifest as intracranial hypertension due
      to mass effect from large cysts or to cerebrospinal fluid flow obstruction by
      intraventricular cysts or inflammation of the subarachnoid space. While the
      condition is endemic in several regions of the world and has been appreciated as
      a public health problem in such regions for several decades, its emergence in the
      USA in areas far from the Mexican border is a more recent phenomenon. METHODS: We
      present a case of surgically corrected acute hydrocephalus in a recent Haitian
      emigrant child due to a third ventricular neurocysticercal cyst complex. RESULTS:
      We describe the endoscope-assisted en bloc removal of the complex, together with
      hydraulic maneuvers facilitating the removal of the intact cyst. CONCLUSIONS:
      Simple hydraulic maneuvers can facilitate the endoscopic en bloc removal of third
      ventricular neurocysticercal cysts.

PMID- 24037382
TI  - Blastomere biopsy influences epigenetic reprogramming during early embryo
      development, which impacts neural development and function in resulting mice.
AB  - Blastomere biopsy is used in preimplantation genetic diagnosis; however, the long
      term implications on the offspring are poorly characterized. We previously
      reported a high risk of memory defects in adult biopsied mice. Here, we assessed
      nervous function of aged biopsied mice and further investigated the mechanism of
      neural impairment after biopsy. We found that aged biopsied mice had poorer
      spatial learning ability, increased neuron degeneration, and altered expression
      of proteins involved in neural degeneration or dysfunction in the brain compared
      to aged control mice. Furthermore, the MeDIP assay indicated a genome-wide low
      methylation in the brains of adult biopsied mice when compared to the controls,
      and most of the genes containing differentially methylated loci in promoter
      regions were associated with neural disorders. When we further compared the
      genomic DNA methylation profiles of 7.5-days postconception (dpc) embryos between
      the biopsy and control group, we found the whole genome low methylation in the
      biopsied group, suggesting that blastomere biopsy was an obstacle to de novo
      methylation during early embryo development. Further analysis on mRNA profiles of
      4.5-dpc embryos indicated that reduced expression of de novo methylation genes in
      biopsied embryos may impact de novo methylation. In conclusion, we demonstrate an
      abnormal neural development and function in mice generated after blastomere
      biopsy. The impaired epigenetic reprogramming during early embryo development may
      be the latent mechanism contributing to the impairment of the nervous system in
      the biopsied mice, which results in a hypomethylation status in their brains. 

PMID- 24037384
TI  - Quantitative measurement of hip protector use and compliance.
AB  - Hip protectors are often prescribed to the elderly who are at risk of falling,
      with the goal of preventing hip fractures. However, determining the effectiveness
      of hip protectors has been hampered by unreliable compliance data. This study
      reports a reliable objective method of measuring compliance and the developed
      method could be used in any climate, regardless of temperature. Custom compliance
      monitors were built and embedded inside hip protectors. An algorithm was
      developed to utilize both temperature and acceleration to determine compliance.
      Seven young volunteers (age 24.6 +/- 4.2 years old) wore the protectors for a
      total of 667 h while closely recording their compliance. One female (77 years
      old) who had hip fracture history wore the compliance monitors for 91.6 % of the
      time during a 1-week stay in a hospital. From the volunteers' trial, using
      temperature alone overpredicted compliance by 1.2 % and using acceleration alone
      overpredicted by 5.4 %, but using a combination of the two methods plus a
      correction factor only underestimated by 0.6 %. From the elderly data, the
      average compliance recorded from the temperature, acceleration, and combined
      methods with correction was 94.6, 88.9, and 90.2, respectively. The high accuracy
      of temperature sensors in this study will not be attainable in hot climates where
      most of the worldwide increase in hip fractures is occurring. The developed
      monitor with the algorithm provided high accuracy in determining compliance and
      was able to determine both the longitudinal and cross-sectional compliance at any
      time.

PMID- 24037385
TI  - Inverse finite-element modeling for tissue parameter identification using a
      rolling indentation probe.
AB  - This paper investigates the use of inverse finite-element modeling (IFEM)-based
      methods for tissue parameter identification using a rolling indentation probe for
      surgical palpation. An IFEM-based algorithm is proposed for tissue parameter
      identification through uniaxial indentation. IFEM-based algorithms are also
      created for locating and identifying the properties of an embedded tumor through
      rolling indentation of the soft tissue. Two types of parameter identification for
      the tissue tumor are investigated (1) identifying the stiffness (MU) of a tumor
      at a known depth and (2) estimating the depth of the tumor (D) with known
      mechanical properties. The efficiency of proposed methods has been evaluated
      through silicone and porcine kidney experiments for both uniaxial indentation and
      rolling indentation. The results show that both of the proposed IFEM methods for
      uniaxial indentation and rolling indentation have good robustness and can rapidly
      converge to the correct results. The tissue properties estimated using the
      developed method are generic and in good agreement with results obtained from
      standard material tests. The estimation error of MU through uniaxial indentation
      is below 3 % for both silicone and kidney; the estimation error of MU for the
      tumor through rolling indentation is 7-9 %. The estimation error of D through
      rolling indentation is 1-2 mm.

PMID- 24037387
TI  - Sequential growth at the sub-10 nm scale of cyanide bridged coordination networks
      on inorganic surfaces.
AB  - The elaboration of coordination networks' nano-objects on surfaces can be
      realized by sequential growth in solution (SGS). This bottom-up strategy gives
      the possibility to control the size, the isolation and the organization of the
      objects with a precision going up to the molecular scale. Detailed descriptions
      of the growth of the nickel(II)-iron(II) Prussian blue analog and of the copper
      molybdenum cyanide-bridged coordination network are reported to give insight
      about the mechanisms of the growth. Then a comparative XPS analysis has been
      performed to explain the different reactivity of the precursors of the growth of
      the nickel(II)-iron(II) and nickel(II)-chromium(III) Prussian blue analogs. This
      perspective article proves that SGS can be optimized for each coordination system
      to build molecular superstructures on surfaces, with interesting physical
      properties towards chemical devices.

PMID- 24037386
TI  - Anatomy of the obesity paradox in heart failure.
AB  - A counterintuitive phenomenon of survival advantage in obese patients with heart
      failure (HF) is called obesity paradox. In this review, we emphasize that in
      nearly all research papers on this subject, there were marked differences between
      the groups with different body mass index (BMI). Surprisingly, these differences
      are very consistent and mostly in favor of patients with higher BMI. Obese
      individuals in HF studies almost invariably were characterized by much younger
      age, better nutritional status, higher blood pressure, less arrhythmia, less
      anemia, less valvular regurgitation, better left ventricular systolic function,
      better lungs, and better renal function. There is no paradox in their better
      survival. None of the studies confirming the obesity paradox were designed as
      prospective studies with the purpose to find the effects of BMI on survival. All
      the studies represent post hoc analysis of clinical trials designed for different
      purposes, or retrospective studies, or analysis of registries. Multiple baseline
      differences of subgroups with different BMI likely contribute to the obesity
      paradox, because not all variables influencing the outcomes can be accounted for.

PMID- 24037388
TI  - Tailoring the protein conformation to synthesize different-sized gold
      nanoclusters.
AB  - Gold nanoclusters with five discrete sizes (Au4, Au8, Au10, Au13, and Au25) are
      synthesized in a protein template with predefined conformation via a CO-mediated
      synthesis. 

PMID- 24037389
TI  - Belief revision and way-finding.
AB  - Belief revision is required when veridical information surfaces that contradicts
      what was previously thought to be the case. In way-finding, belief revision
      frequently occurs, for example, when the travelled route has led one astray,
      instead of to one's chosen destination. In past cognitive research, the topics of
      belief revision and way-finding have been treated in isolation. Here, we
      introduce an approach for linking the two fields and assess belief revision as it
      occurs in the process of way-finding. We report the results of two experiments
      that put participants in (virtual) situations where elements of a previously
      learned route description do not match the actual environment (thereby requiring
      the revision of a previously held belief). Experiment 1 puts participants in a
      highly artificial virtual environment where the landmarks to be used in
      navigation have a low degree of semantic salience (houses of various color).
      Experiment 2 puts subjects in a photorealistic environment where the objects to
      be used in navigation are well-known landmarks (such as the Eiffel Tower) and
      thus have a high degree of semantic salience. In both experiments, participants
      are confronted with T-junctions, where a landmark that was expected to indicate
      the correct route is discovered to be in an unexpected location. The results of
      the experiments show that a participant's choice of route, in such cases, is
      affected by differences in the structure of the relevant initial instruction.
      More precisely, the route chosen by participants is affected by whether the
      relevant landmark was described as being on the same side of the path as they
      were instructed to turn (congruent case) or as located on the opposite side of
      the path as they were instructed to turn (incongruent case). 

PMID- 24037390
TI  - The RCN just doesn't get it.

PMID- 24037391
TI  - Are nurse-led mutuals the future of NHS care delivery?

PMID- 24037392
TI  - Hand hygiene and the use of personal protective equipment.
AB  - Infection prevention and control nurses (IPCNs) have an extremely wide remit in
      relation to the facilitation of appropriate infection prevention and control
      practice within healthcare environments. In order to be effective IPCNs need to
      be involved at all stages of healthcare service delivery and need to form close
      working relationships with staff at all levels and in all departments within
      their organisation. The provision of the necessary facilities within the clinical
      environment, along with the ongoing training and support of staff are essential
      prerequisites to changing the behaviour of staff in order to consistently deliver
      effective hand hygiene and other infection prevention and control practices.
      Auditing of practice and the investigation of incidents enable the identification
      of areas of practice requiring improvement, which subsequently informs the
      continual development of training programmes and initiatives with a view to
      improving patient and staff safety. IPCNs need to be able to react swiftly to the
      emergence of new infectious organisms and/or evidence to identify what is
      required in order to ensure that staff are compliant with anticipated practice to
      maintain the safety of the patients in their care, themselves and their
      colleagues. 

PMID- 24037393
TI  - Disinfectants in health care: finding an alternative to chlorine dioxide.
AB  - Cleanliness of the clinical environment has a direct impact on healthcare
      associated infection (HCAI) incidence and there is increasing evidence of its
      importance with regard to infection prevention and control. While traditional
      high-level disinfectants have excellent antimicrobial properties, these are
      typically offset against issues such as corrosiveness, toxicity, cost and user
      acceptance. Recent years have seen several user-friendly sporicidal disinfectants
      emerge onto the market. Antimicrobial profile and user acceptance determine the
      clinical success of any disinfectant. Therefore, product adoption is often a two
      stage process with a tabletop evaluation of the appropriate technical data,
      including efficacy claims, followed by an in-use product evaluation. The first
      part of this article demonstrates the importance of the clinical environment with
      respect to HCAI and examines some of the issues around disinfectants used in
      health care and considerations when selecting a new disinfectant for use. The
      second part reports the experiences of the Infection Prevention and Control team
      at Alder Hey Children's Hospital in their assessment and subsequent adoption of a
      new user-friendly sporicidal disinfectant into clinical practice. 

PMID- 24037394
TI  - Clinical competency assessment in intravenous therapy and vascular access: part
      1.
AB  - Nurse training and education programmes have changed in recent years, moving from
      a 'learning on the job' process of training and learning to a much more
      structured and academic approach. As professionals in health, we must continually
      update and refresh our knowledge and skills (Mann et al, 2009), a view supported
      by Fry et al (2003) who highlight that nurses are now encouraged to continue with
      lifelong learning. The Nursing and Midwifery Council (NMC) Code of Conduct 40
      states: 'You must keep your knowledge and skills up to date throughout your
      working life'. Code 41 states: 'You must take part in appropriate learning and
      practice activities that maintain and develop your competence' (NMC, 2010).
      Within the hospital setting, most patients will receive some form of intravenous
      therapy (IV) treatment (Peterson, 2002: cited by RCN, 2010). Infusion therapy has
      therefore become an integral part of professional practice for most nurses, who
      must learn the initial skills in IV therapy and vascular access and achieve
      clinical competence. Education and clinical training by specialist teams in
      organisations must be delivered to ensure safe skills are learnt (RCN, 2010).
      This education and training must incorporate both theoretical and practical
      elements, with appropriate means of assessment. The delivery methods should be
      diverse, recognising that individuals have different approaches to learning.
      Clinical competency assessment frameworks are widely used within nurse education.
      But are they the most appropriate method of assessment, or can other methods be
      used? An in-depth literature review in this paper will highlight different
      approaches to learning, assessment and clinical competence. 

PMID- 24037395
TI  - The biologics era: a revolution in arthritis management.

PMID- 24037396
TI  - Advancing practice: from staff nurse to nurse consultant Part 4: using clinical
      supervision.

PMID- 24037397
TI  - Assessment of body temperature measurement options.
AB  - Assessment of body temperature is important for decisions in nursing care,
      medical diagnosis, treatment and the need of laboratory tests. The definition of
      normal body temperature as 37 degrees C was established in the middle of the 19th
      century. Since then the technical design and the accuracy of thermometers has
      been much improved. Knowledge of physical influence on the individual body
      temperature, such as thermoregulation and hormones, are still not taken into
      consideration in body temperature assessment. It is time for a change; the
      unadjusted mode should be used, without adjusting to another site and the same
      site of measurement should be used as far as possible. Peripheral sites, such as
      the axillary and the forehead site, are not recommended as an assessment of core
      body temperature in adults. Frail elderly individuals might have a low normal
      body temperature and therefore be at risk of being assessed as non-febrile. As
      the ear site is close to the hypothalamus and quickly responds to changes in the
      set point temperature, it is a preferable and recommendable site for measurement
      of body temperature. 

PMID- 24037398
TI  - Exploring the role of the inflammatory bowel disease nurse specialist.
AB  - The number of inflammatory bowel disease (IBD) nurses and the amount of
      biological therapies being used in IBD has proliferated over the past ten years.
      Coordinating and managing a biologics service requires highly skilled specialist
      nursing knowledge and awareness of the support, assessment, administration and
      monitoring required in supporting the patient through this pathway. This article
      explores the role of the nurse and clinical issues in managing patients receiving
      biological therapies. 

PMID- 24037399
TI  - The end of one journey, the start of another.
AB  - Deborah Easby, who has been a nursing student at Sheffield Hallam University, is
      on the brink of starting her first job. Here she looks back on her training and
      looks forward to her future as a qualified critical care nurse. She also has some
      tips for those starting out on the same journey. 

PMID- 24037400
TI  - Nurses need a standard definition of a deprivation of liberty.
AB  - The House of Commons health committee has called for an urgent review of the
      implementation of the deprivation of liberty safeguards. They are particularly
      concerned that nurses, as gatekeepers of the safeguards, often do not know when a
      deprivation of liberty occurs in practice. In this article the author argues that
      given the lack of a standard definition of what amounts to a deprivation of
      liberty and the introduction by the courts of often contradictory factors that
      nurses are required to consider when determining if a patient is being deprived
      of their liberty it is little wonder that confusion is common place. 

PMID- 24037401
TI  - Writing for publication: science and healthcare journals.
AB  - This article is designed to help authors write scholarly articles for publication
      in science and healthcare journals. A comprehensive model based on 11 steps and
      detailing the structure expected for a journal is suggested for the writing of a
      range of papers. This is in keeping with the recognised style of a number of
      academic journals. The article encourages authors to submit their papers for
      publication with the intention of enhancing the quality and safety of care
      provided to patients, clients and service users. 

PMID- 24037402
TI  - The effect of stress on health and its implications for nursing.
AB  - Stress is an important issue within nursing and it is difficult to find agreement
      among those who are expert in the area regarding a concise definition of stress.
      Nevertheless stress is seen as a negative feeling affecting people's health
      either physically and/or psychologically. However, stress is a normal part of
      life and considered necessary to increase functional capacity, whereas stress
      over a prolonged period or when extreme can cause distress which may have
      debilitating effects that reduce work output, increase absenteeism and reduce
      one's ability to cope with situations. The most important resource in any
      organisation is the employee; therefore maintaining and supporting their health
      is vital to ensure their ability to work, maintain standards and continuously
      improve standards of care. Leadership styles within organisations must facilitate
      staff to be involved in decision making; thereby staff feel more valued and work
      in an autonomous way. This article identifies and discusses the effect of stress
      on health and its relationship to nursing. 

PMID- 24037403
TI  - Improving health care for the vulnerable elderly in society.

PMID- 24037404
TI  - Why the Liverpool Care Pathway should be replaced.

PMID- 24037405
TI  - Nurses - let's be proud together.

PMID- 24037407
TI  - TRAIL and microRNAs in the treatment of prostate cancer: therapeutic potential
      and role of nanotechnology.
AB  - Disruption of spatiotemporal behavior of intracellular signaling cascades
      including tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)
      mediated signaling in prostate cancer has gained tremendous attention in the past
      few years. There is an increasing effort in translating the emerging information
      about TRAIL-mediated signaling obtained through experimental and preclinical data
      to clinic. Fascinatingly, novel targeting approaches are being developed to
      enhance the tissue- or subcellular-specific delivery of drugs with considerable
      focus on prostate cancer. These applications have the potential to revolutionize
      prostate cancer therapeutic strategies and include the accumulation of drugs in
      target tissue as well as the selection of internalizing ligands for enhanced
      receptor-mediated uptake of drugs. In this mini-review, we outline outstanding
      developments in therapeutic strategies based on the regulation and/or targeting
      of TRAIL pathway for the treatment of prostate cancer. Moreover, microRNAs
      (miRNAs), with potential transcriptional and posttranscriptional regulation of
      gene expression, will be presented for their potential in prostate cancer
      treatment. Emphasis has been given to the use of delivery approaches, especially
      based on nanotechnology. Considerably, enhanced information regarding miRNA
      regulation of TRAIL-mediated signaling in prostate cancer cells may provide
      potential biomarkers for the characterization of patients as responders and
      nonresponders of TRAIL-based therapy and could provide rationalized basis for
      combination therapies with TRAIL death receptor-targeting drugs.

PMID- 24037408
TI  - Challenges of formulation and quality of biofertilizers for successful
      inoculation.
AB  - The interest in biofertilizers is increasing and so is the potential for their
      use in sustainable agriculture. However, many of the products that are currently
      available worldwide are often of very poor quality, resulting in the loss of
      confidence from farmers. The formulation of an inoculant is a crucial multistep
      process that should result in one or several strains of microorganisms included
      in a suitable carrier, providing a safe environment to protect them from the
      often harsh conditions during storage and ensuring survival and establishment
      after introduction into soils. One of the key issues in formulation development
      and production is the quality control of the products, at each stage of the
      process. This review presents the different components and the major steps
      involved in the formulation of good quality biofertilizers, including the
      techniques used to assess the quality of the products following production. The
      quality of currently available inoculants is also reviewed, emphasizing the need
      for better quality control systems worldwide.

PMID- 24037406
TI  - Recombinant Aspergillus beta-galactosidases as a robust glycomic and
      biotechnological tool.
AB  - Galactosidases are widespread enzymes that are used for manifold applications,
      including production of prebiotics, biosynthesis of different transgalactosylated
      products, improving lactose tolerance and in various analytical approaches. The
      nature of these applications often require galactosidases to be present in a
      purified form with clearly defined properties, including precisely determined
      substrate specificities, low sensitivity to inhibitors, and high efficiency and
      stability under distinct conditions. In this study, we present the recombinant
      expression and purification of two previously uncharacterized beta-galactosidases
      from Aspergillus nidulans as well as one beta-galactosidase from Aspergillus
      niger. All enzymes were active toward p-nitrophenyl-beta-D-galactopyranoside as
      substrate and displayed similar temperature and pH optima. The purified
      recombinant galactosidases digested various complex substrates containing
      terminal galactose beta-1,4 linked to either N-acetylglucosamine or fucose, such
      as N-glycans derived from bovine fibrin and Caenorhabditis elegans. In our
      comparative study of the recombinant galactosidases with the commercially
      available galactosidase from Aspergillus oryzae, all enzymes also displayed
      various degrees of activity toward complex oligosaccharides containing beta-1,3
      linked terminal galactose residues. All recombinant enzymes were found to be
      robust in the presence of various organic solvents, temperature variations, and
      freeze/thaw cycles and were also tested for their ability to synthesize
      galactooligosaccharides. Furthermore, the use of fermentors considerably
      increased the yield of recombinant galactosidases. Taken together, we demonstrate
      that purified recombinant galactosidases from A. niger and from A. nidulans are
      suitable for various glycobiological and biotechnological applications. 

PMID- 24037409
TI  - Reference gene selection in Carnobacterium maltaromaticum, Lactobacillus
      curvatus, and Listeria innocua subjected to temperature and salt stress.
AB  - Eight putative consistently expressed genes in Carnobacterium maltaromaticum and
      Lactobacillus curvatus, and nine in Listeria innocua, were examined for their
      potential as references for the normalization of gene expression. Expression
      stability of candidate reference genes was evaluated under growth conditions of
      low (5  degrees C) and moderately high (40-42.5  degrees C) temperatures, and
      high salt (>=3 % NaCl) using the geNormplus and NormFinder algorithms. Under
      temperature stress, both algorithms ranked elongation factor Tu (Tuf) as the most
      stably expressed gene in C. maltaromaticum. In L. curvatus, at similar
      conditions, geNormplus identified Tuf and 6-phosphogluconate dehydrogenase
      (6PGDH) as suitable for normalization, while NormFinder identified phenylalanyl
      tRNA synthase and recombinase A as the best pair. In L. innocua grown under the
      same temperatures, geNormplus ranked 6PGDH, glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH), and Tuf as the top three most stable references, whereas
      NormFinder identified GAPDH and 6PGDH as suitable for normalization, with Tuf
      ranked as number six. There was less consistency between algorithms in the salt
      stress experiment. No gene was identified that exhibited such a constant level of
      expression as to outperform the other candidates under both experimental
      conditions. This study underlines the need for normalizing bacterial gene
      expression using multiple carefully selected references. 

PMID- 24037410
TI  - Comparative effect of human platelet derivatives on proliferation and osteogenic
      differentiation of menstrual blood-derived stem cells.
AB  - Menstrual blood has been recognized as an easily accessible and inexpensive
      source of stem cells, in recent years. To establish a safe and efficient protocol
      for development of menstrual blood-derived stem cells (MenSCs) into osteoblasts,
      the effect of substitution of fetal bovine serum (FBS) with human platelet
      derivatives (HPDs) was evaluated during proliferation and osteogenic
      differentiation of MenSCs. To this aim, parallel experiments were carried out on
      cultured MenSCs in the presence of platelet-rich plasma, platelet-poor plasma,
      platelet gel supernatant, or human platelet releasate (HPR), and compared with
      cells cultured in conventional growth medium containing FBS. There was no
      significant difference between growth curves of cultured MenSCs in presence of
      different fortified media. However, the MenSCs demonstrated variant
      differentiation patterns in response to FBS replacement with HPDs.
      Mineralization, as judged by Alizarin red staining, was significantly higher in
      cells differentiated in the presence of HPR compared to cells that were fortified
      with other medium supplements. A greater osteocalcin production level, alkaline
      phosphatase activity, and mRNA expression of osteogenic-specific genes in
      differentiated MenSCs under HPR condition further confirmed our previous
      findings. Based on our data, FBS substitution by HPDs not only allows for
      successful MenSCs proliferation, but also promotes MenSCs development into
      osteoblasts. The effectiveness of HPR on osteogenic differentiation of MenSCs
      represents an important novel step toward safe and applied stem cell therapy of
      bone diseases. 

PMID- 24037411
TI  - Mutation of tyrosine167histidine at remote substrate binding subsite -6 in alpha
      cyclodextrin glycosyltransferase enhancing alpha-cyclodextrin specificity by
      directed evolution.
AB  - alpha-Cyclodextrin glycosyltransferase (alpha-CGTase) can convert starch into
      alpha-cyclodextrin with various proportions of beta-cyclodextrin and/or gamma
      cyclodextrin in the products. To improve the alpha-cyclodextrin-forming
      specificity, directed evolution on the wild-type alpha-CGTase was performed by
      constructing mutant library with error-prone PCR method. The positive mutant
      strains were selected in combination of starch plate screening with HPLC
      detection of the products. An alpha-CGTase from the mutant strain (assigned No.
      95) was found to be able to increase the alpha:beta ratio in product mixture from
      3.4 to 7.8 in comparison with the wild-type alpha-CGTase. Sequence alignment
      indicated that two mutations occurred in the No. 95 mutant alpha-CGTase, which
      were Y167H and A536V. Reverse mutation revealed that Y167H was responsible for
      this change. A series of 167 site-substituted mutants could improve the
      alpha:beta ratio to different extents as indicated by saturated mutagenesis, with
      Y167H as the best substitution. In conclusion, Y167 was confirmed to be one of
      the main subsites in the -6 domain of alpha-CGTase that is responsible for the
      alpha:beta ratio in the product mixture. Y167H is most preferable among all types
      of mutant enzymes tested at this site. The reconstructed Y167H (i.e., No. 95)
      alpha-CGTase showed better potential for alpha-cyclodextrin production on
      industrial scale. 

PMID- 24037412
TI  - What do cancer patients worry about when making decisions about treatment?
      Variation across racial/ethnic groups.
AB  - The aim of this study was to determine the issues patients worry about when
      making decisions about cancer treatment. A total of 5,044 colorectal and lung
      cancer patients from the Cancer Care Outcomes Research and Surveillance
      Consortium reported their level of worry about (1) treatment side effects, (2)
      treatment costs, (3) time away from family, (4) time away from work, and (5)
      transportation to treatment sites. Using multivariable logistic regression, we
      evaluated the association of sociodemographic, clinical, and psychosocial
      variables with worry. Overall, 75 % of patients worried about side effects of
      treatments; 40 %, the cost of treatment; 50 %, time away from family; 52 %, time
      away from work; and 22 %, about transportation. In multivariable analyses, across
      all worry domains, older patients had lower odds of reporting worry (p values <
      0.001). Patients who perceived less than excellent quality of care, self-assessed
      their health as less than excellent, and those with a higher cancer stage were
      more likely to report worry. Asian patients were more likely to report worry than
      Whites about the cost of treatment and transportation, and relative to Whites,
      Hispanics were more likely to report worry about transportation (p values <
      0.05). Black patients were less likely to report worry about time away from work.
      Patients worry about issues beyond treatment side effects when making treatment
      decisions. The pattern of worry varies along sociodemographic, clinical, and
      psychosocial factors, including race and ethnicity. Understanding the source of
      patient worry and identifying interventions to alleviate worry are important to
      delivering patient-centered cancer care.

PMID- 24037413
TI  - Consultation with specialist palliative care services in palliative sedation:
      considerations of Dutch physicians.
AB  - PURPOSE: Palliative sedation is considered a normal medical practice by the Royal
      Dutch Medical Association. Therefore, consultation of an expert is not considered
      mandatory. The European Association of Palliative Care (EAPC) framework for
      palliative sedation, however, is more stringent: it considers the use of
      palliative sedation without consulting an expert as injudicious and insists on
      input from a multi-professional palliative care team. This study investigates the
      considerations of Dutch physicians concerning consultation about palliative
      sedation with specialist palliative care services. METHODS: Fifty-four physicians
      were interviewed on their most recent case of palliative sedation. RESULTS:
      Reasons to consult were a lack of expertise and the view that consultation was
      generally supportive. Reasons not to consult were sufficient expertise, the view
      that palliative sedation is a normal medical procedure, time pressure, fear of
      disagreement with the service and regarding consultation as having little added
      value. Arguments in favour of mandatory consultation were that many physicians
      lack expertise and that palliative sedation is an exceptional intervention.
      Arguments against mandatory consultation were practical obstacles that may
      preclude fulfilling such an obligation (i.e. lack of time), palliative sedation
      being a standard medical procedure, corroding a physician's responsibility and
      deterring physicians from applying palliative sedation. CONCLUSION: Consultation
      about palliative sedation with specialist palliative care services is regarded as
      supportive and helpful when physicians lack expertise. However, Dutch physicians
      have both practical and theoretical objections against mandatory consultation.
      Based on the findings in this study, there seems to be little support among Dutch
      physicians for the EAPC recommendations on obligatory consultation.

PMID- 24037414
TI  - Translucent tissue defect in potato (Solanum tuberosum L.) tubers is associated
      with oxidative stress accompanying an accelerated aging phenotype.
AB  - Translucent tissue defect (TTD) is an undesirable postharvest disorder of potato
      tubers characterized by the development of random pockets of semi-transparent
      tissue containing high concentrations of reducing sugars. Translucent areas turn
      dark during frying due to the Maillard reaction. The newly released cultivar,
      Premier Russet, is highly resistant to low temperature sweetening, but
      susceptible to TTD. Symptoms appeared as early as 170 days after harvest and
      worsened with time in storage (4-9  degrees C, 95 % RH). In addition to higher
      concentrations of glucose, fructose and sucrose, TTD resulted in lower dry
      matter, higher specific activities of starch phosphorylase and glc-6-phosphate
      dehydrogenase, higher protease activity, loss of protein, and increased
      concentrations of free amino acids (esp. asparagine and glutamine). The mechanism
      of TTD is unknown; however, the disorder has similarities with the irreversible
      senescent sweetening that occurs in tubers during long-term storage, where much
      of the decline in quality is a consequence of progressive increases in oxidative
      stress with advancing age. The respiration rate of non-TTD 'Premier Russet'
      tubers was inherently higher (ca. 40 %) than that of 'Russet Burbank' tubers (a
      non-TTD cultivar). Moreover, translucent tissue from 'Premier Russet' tubers had
      a 1.9-fold higher respiration rate than the average of non-translucent tissue and
      tissue from non-TTD tubers. Peroxidation of membrane lipids during TTD
      development resulted in increased levels of malondialdehyde and likely
      contributed to a measurable increase in membrane permeability. Superoxide
      dismutase and catalase activities and the ratio of oxidized to total glutathione
      were substantially higher in translucent tissue. TTD tubers also contained
      twofold less ascorbate than non-TTD tubers. TTD appears to be a consequence of
      oxidative stress associated with accelerated aging of 'Premier Russet' tubers.

PMID- 24037415
TI  - Asthma and allergy: a fibrinogen root to airway inflammation.

PMID- 24037416
TI  - Pattern recognition receptors: DNA damage drives detection.

PMID- 24037417
TI  - Mucosal immunology: air miles for T cells.

PMID- 24037419
TI  - Cell adhesion to fibronectin down-regulates the expression of Spy1 and
      contributes to drug resistance in multiple myeloma cells.
AB  - Spy1 is a member of the Speedy/Ringo family, which regulates cell proliferation
      and survival. Spy1 has been demonstrated to promote the cell-cycle progress
      through p27(Kip1) degradation. Previous investigations have suggested cell
      adhesion-mediated drug resistance (CAM-DR) in multiple myeloma (MM) is a primary
      factor for minimal residual disease (MRD) leading to relapse after chemotherapy.
      However, the precise mechanism remains elusive. In this study, we used MM cell
      lines to determine whether Spy1 plays a role in CAM-DR. We demonstrated that
      adhesion of MM cells to fibronectin (FN) decreased Spy1 expression.
      Overexpression of Spy1 did not affect MM cells adhesion to FN, but did reverse
      the doxorubicin- or mitoxantrone-induced CAM-DR phenotype. Spy1 protein level was
      also correlated with reciprocal up-regulation of p27(Kip1) when RPMI 8226 cells
      bound FN. Spy1 overexpression promoted p27(Kip1) phosphorylation at T187, then
      induced the p27(Kip1) degradation in the adhesion model. In addition, increasing
      p27(Kip1) level or disturbing p27(Kip1) phosphorylation at T187 abolished the CAM
      DR reversion when Spy1 was overexpressed. Collectively, our data suggest that
      Spy1 plays an important role in CAM-DR, which depends on the function of
      p27(Kip1). Our findings provide a rational framework for further development of
      Spy1 as a novel target for MM therapy.

PMID- 24037418
TI  - The immune system and kidney disease: basic concepts and clinical implications.
AB  - The kidneys are frequently targeted by pathogenic immune responses against renal
      autoantigens or by local manifestations of systemic autoimmunity. Recent studies
      in rodent models and humans have uncovered several underlying mechanisms that can
      be used to explain the previously enigmatic immunopathology of many kidney
      diseases. These mechanisms include kidney-specific damage-associated molecular
      patterns that cause sterile inflammation, the crosstalk between renal dendritic
      cells and T cells, the development of kidney-targeting autoantibodies and
      molecular mimicry with microbial pathogens. Conversely, kidney failure affects
      general immunity, causing intestinal barrier dysfunction, systemic inflammation
      and immunodeficiency that contribute to the morbidity and mortality of patients
      with kidney disease. In this Review, we summarize the recent findings regarding
      the interactions between the kidneys and the immune system. 

PMID- 24037420
TI  - Are MPNs vascular diseases?
AB  - A high risk of arterial and venous thrombosis is the hallmark of chronic
      myeloproliferative neoplasms (MPNs), particularly polycythemia vera (PV) and
      essential thrombocythemia (ET). Clinical aspects, pathogenesis and management of
      thrombosis in MPN resemble those of other paradigmatic vascular diseases. The
      occurrence of venous thrombosis in atypical sites, such as the splanchnic
      district, and the involvement of plasmatic prothrombotic factors, including an
      acquired resistance to activated protein C, both link MPN to inherited
      thrombophilia. Anticoagulants are the drugs of choice for these complications.
      The pathogenic role of leukocytes and inflammation, and the high mortality rate
      from arterial occlusions are common features of MPN and atherosclerosis. The
      efficacy and safety of aspirin in reducing deaths and major thrombosis in PV have
      been demonstrated in a randomized clinical trial. Finally, the Virchow's triad of
      impaired blood cells, endothelium and blood flow is shared both by MPN and
      thrombosis in solid cancer. Phlebotomy and myelosuppressive agents are the
      current therapeutic options for correcting these abnormalities and reducing
      thrombosis in this special vascular disease represented by MPN.

PMID- 24037422
TI  - Stress resistance and C1 metabolism involved in plant colonization of a
      methanotroph Methylosinus sp. B4S.
AB  - Methanotrophs are widespread and have been isolated from various environments
      including the phyllosphere. In this study, we characterized the plant
      colonization by Methylosinus sp. B4S, an alpha-proteobacterial methanotroph
      isolated from plant leaf. The gfp-tagged Methylosinus sp. B4S cells were observed
      to colonize Arabidopsis leaf surfaces by forming aggregates. We cloned and
      sequenced the general stress response genes, phyR, nepR and ecfG, from
      Methylosinus sp. B4S. In vitro analysis showed that the phyR expression level was
      increased after heat shock challenge, and phyR was shown to be involved in
      resistance to heat shock and UV light. In the phyllospheric condition, the gene
      expression level of phyR as well as mmoX and mxaF was found to be relatively
      high, compared with methane-grown liquid cultures. The phyR-deletion strain as
      well as the wild-type strain inoculated on Arabidopsis leaves proliferated at the
      initial phase and then gradually decreased during plant colonization. These
      results have shed light firstly on the importance of general stress resistance
      and C1 metabolism in methanotroph living in the phyllosphere. 

PMID- 24037421
TI  - E2F1-mediated DNA damage is implicated in 8-Cl-adenosine-induced chromosome
      missegregation and apoptosis in human lung cancer H1299 cells.
AB  - Although E2F1-mediated DNA double-stranded breaks (DSBs) and tetraploid have been
      extensively studied, the role of E2F1 in mitotic catastrophe is still unknown. We
      have previously shown that 8-chloro-adenosine (8-Cl-Ado) induces DNA DSBs and
      aberrant mitosis in human lung cancer cells, followed by delayed apoptosis. Here,
      we demonstrate that E2F1-mediated DNA damage is implicated in 8-Cl-Ado-induced
      chromosome missegregation and apoptosis in lung cancer H1299 cells. We showed
      that E2F1 was accumulated upon 8-Cl-Ado-induced DNA DSBs. Induction of E2F1 by 8
      Cl-Ado caused DNA damage in cycling cells including M cells. In contrast,
      silencing of E2F1 expression decreased 8-Cl-Ado-induced DNA DSBs, particularly
      eliminated E2F1-mediated mitotic DNA damage. Over-expression of E2F1 and/or 8-Cl
      Ado exposure resulted in aberrant mitotic spindles and chromosome segregation
      errors. Furthermore, over-expression of E2F1 expression enhanced 8-Cl-Ado-induced
      apoptosis. Together, our data indicate that E2F1-mediated DNA damage, in
      particular mitotic DNA damage, is an important fraction of 8-Cl-Ado-induced DNA
      damage, which is implicated in 8-Cl-Ado-induced mitotic catastrophe and delayed
      apoptosis. Induction of E2F1 by 8-Cl-Ado may contribute at least partly to the
      drug-inhibited proliferation of cancer cells. 

PMID- 24037423
TI  - Asymmetric ring-opening of oxabenzonorbornadiene with amines promoted by a chiral
      iridium-monophosphine catalyst.
AB  - A new iridium-monophosphine catalyst is found to be efficient for asymmetric ring
      opening of benzonorbornadiene with amines, providing a series of chiral
      substituted dihydronaphthalenes in high yields (up to 98%) and excellent
      enantioselectivities (>99%). 

PMID- 24037424
TI  - An association between nuclear morphology and immunohistochemical expression of
      p53 and p16INK4A in lung cancer cells.
AB  - Nuclear atypia is one of the most important morphological features used to
      diagnose malignant neoplasms. The potential molecular alteration that causes
      nuclear atypia remains unknown. P53 and p16INK4A play crucial roles in cell cycle
      checkpoints and repairing DNA damage to maintain integrity of the genome. Thus,
      inactivation of p53 and p16INK4A has been hypothesized to alter the chromatin
      structure and result in nuclear atypia. This study examined 201 primary lung
      cancers for the immunohistochemical expression of p53 and p16INK4A, and analyzed
      potential associations with the essential elements of nuclear atypia, such as
      nuclear size, circularity of the outline, and the density and granularity of
      chromatin. Tumors that expressed high levels of p53 had larger nuclei with higher
      chromatin density and distorted nuclear outlines. Tumors that expressed low
      levels of p16INK4 had larger nuclei with distorted nuclear outlines. Thus,
      alterations in p53 and p16INK4A may be the potential cause of nuclear atypia in
      neoplastic cells. 

PMID- 24037426
TI  - CO2 selective dynamic two-dimensional Zn(II) coordination polymer.
AB  - A CO2 selective dynamic two-dimensional (2D) MOF system, [Zn(glu)(MU-bpe)].2H2O
      (.2H2O) (glu = glutarate, bpe = 1,2-bis(4-pyridyl)ethylene), is prepared. Based
      on variable temperature PXRD patterns, I.2H2O exhibits a structural
      transformation of the framework upon desolvation. Various gas sorption analyses
      at low temperatures reveal that solvent-free I selectively adsorbs CO2 over N2,
      H2, and CH4. Stepped CO2 isotherms for solvent-free I with a large hysteresis
      between adsorption and desorption branches at 196 K indicate that I is a dynamic
      framework. Moreover, I.2H2O shows efficient heterogeneous catalytic reactivity
      for transesterification of various esters. The catalyst can be recycled multiple
      times without losing its original activity.

PMID- 24037425
TI  - Reproducibility of high-throughput mRNA and small RNA sequencing across
      laboratories.
AB  - RNA sequencing is an increasingly popular technology for genome-wide analysis of
      transcript sequence and abundance. However, understanding of the sources of
      technical and interlaboratory variation is still limited. To address this, the
      GEUVADIS consortium sequenced mRNAs and small RNAs of lymphoblastoid cell lines
      of 465 individuals in seven sequencing centers, with a large number of
      replicates. The variation between laboratories appeared to be considerably
      smaller than the already limited biological variation. Laboratory effects were
      mainly seen in differences in insert size and GC content and could be adequately
      corrected for. In small-RNA sequencing, the microRNA (miRNA) content differed
      widely between samples owing to competitive sequencing of rRNA fragments. This
      did not affect relative quantification of miRNAs. We conclude that distributing
      RNA sequencing among different laboratories is feasible, given proper
      standardization and randomization procedures. We provide a set of quality
      measures and guidelines for assessing technical biases in RNA-seq data. 

PMID- 24037429
TI  - Hemodynamics in rat liver tumor model during retrograde-outflow isolated hepatic
      perfusion with aspiration from the portal vein: angiography and in vivo
      microscopy.
AB  - BACKGROUND: Orthograde percutaneous isolated hepatic perfusion (IHP) techniques
      using balloon occlusion catheters are relatively simple and facilitate repeated
      therapy, but they result in higher rates of leakage from the perfusion circuit
      into the systemic circulation. Therefore, a feasible protocol for percutaneous
      IHP with less leakage is required. PURPOSE: To investigate hemodynamic changes in
      rat liver and tumor during retrograde-outflow isolated hepatic perfusion (R-IHP)
      with aspiration from the portal vein (PV). MATERIAL AND METHODS: Animal
      experiments were approved by the Animal Experiment Ethics Committee of Lund
      University. Eighteen rats underwent R-IHP after laparotomy and catheterization of
      the PV and hepatic artery (HA). The HA, inferior vena cava (IVC), and PV were
      ligated, and flow through the suprahepatic IVC was controlled with a suture loop.
      The rats were divided into two groups to examine blood flow during R-IHP. Four
      rats (group 1) underwent arteriography via the HA with and without R-IHP, and 14
      rats (group 2) were inoculated with tumor and examined by in vivo fluorescence
      microscopy of liver and tumor during R-IHP. RESULTS: In group 1, hepatic
      arteriography during R-IHP confirmed arterioportal communication in all four
      rats, with the PV acting as an outflow tract. In vivo fluorescence microscopy in
      group 2 showed strong enhancement of tumors, and no blood supply from the portal
      venules to the tumors was seen in any of the 14 rats. Blood flow in the major
      portion of the hepatic lobules was stopped and the percentage of enhanced area
      was significantly lower in the normal hepatic lobules than in the tumors (P <
      0.0001). CONCLUSION: We confirmed reversal of blood flow concomitant with good
      perfusion of the liver tumor and with reduced perfusion of normal liver
      parenchyma during R-IHP.

PMID- 24037428
TI  - Treatment of myoclonus.
AB  - Myoclonus creates significant disability for patients. This symptom or sign can
      have many different etiologies, presentations, and pathophysiological mechanisms.
      A thorough evaluation for the myoclonus etiology is critical for developing a
      treatment strategy. The best etiological classification scheme is a modified
      version from that proposed by Marsden et al. in 1982. Clinical neurophysiology,
      as assessed by electromyography and electroencephalography, can be used to
      classify the pathophysiology of the myoclonus using a neurophysiology
      classification scheme. If the etiology of the myoclonus cannot be reversed or
      treated, then symptomatic treatment of the myoclonus itself may be warranted.
      Unfortunately, there are few controlled studies for myoclonus treatments. The
      treatment strategy for the myoclonus is best derived from the neurophysiology
      classification scheme categories: 1) cortical, 2) cortical-subcortical, 3)
      subcortical-nonsegmental, 4) segmental, and 5) peripheral. A cortical physiology
      classification is most common. Levetiracetam is suggested as first-line treatment
      for cortical myoclonus, but valproic acid and clonazepam are commonly used.
      Cortical-subcortical myoclonus is the physiology demonstrated by myoclonic
      seizures, such as in primary epileptic myoclonus (e.g., juvenile myoclonic
      epilepsy). Valproic acid has demonstrated efficacy in such epileptic syndromes
      with other medications providing an adjunctive role. Clonazepam is used for
      subcortical-nonsegmental myoclonus, but other treatments, depending on the
      syndrome, have been used for this physiological type of myoclonus. Segmental
      myoclonus is difficult to treat, but clonazepam and botulinum toxin are used.
      Botulinum toxin is used for focal examples of peripheral myoclonus. Myoclonus
      treatment is commonly not effective and/or limited by side effects. 

PMID- 24037430
TI  - Localization and prediction of malignant potential in recurrent
      pheochromocytoma/paraganglioma (PCC/PGL) using 18F-FDG PET/CT.
AB  - BACKGROUND: To our knowledge, data are lacking on the role of 18F-FDG PET/CT in
      the localization and prediction of neuroendocrine tumors, in particular the
      pheochromocytoma/paraganglioma (PCC/PGL) group. PURPOSE: To evaluate the role of
      18F-FDG PET/CT in localizing and predicting the malignant potential of PCC/PGL.
      MATERIAL AND METHODS: Twenty-three consecutive patients with a history of
      PCC/PGL, presenting with symptoms related to catecholamine excess, underwent 18F
      FDG PET/CT. Final confirmation of the diagnosis was made using the composite
      references. PET/CT findings were analyzed on a per-lesion basis and a per-patient
      basis. Tumor SUVmax was analyzed to predict the dichotomization of patient
      endpoints for the local disease and metastatic groups. RESULTS: We investigated
      23 patients (10 men, 13 women) with a mean age of 46.43 +/- 3.70 years. Serum
      catecholamine levels were elevated in 82.60% of these patients. There were 136
      sites (mean SUVmax: 16.39 +/- 3.47) of validated disease recurrence. The overall
      sensitivities for diagnostic CT, FDG PET, and FDG PET/CT were 86.02%, 87.50%, and
      98.59%, respectively. Based on the composite references, 39.10% of patients had
      local disease. There were significant differences in the SUVmax distribution
      between the local disease and metastatic groups; a significant correlation was
      noted when a SUVmax cut-off was set at 9.2 (P<0.05). CONCLUSION: In recurrent
      PCC/PGL, diagnostic 18F-FDG PET/CT is a superior tool in the localization of
      recurrent tumors. Tumor SUVmax is a potentially useful predictor of malignant
      tumor potential.

PMID- 24037427
TI  - Sirtuin deacetylases as therapeutic targets in the nervous system.
AB  - Sirtuins are a conserved family of deacetylases whose activities are dependent on
      nicotinamide adenine dinucleotide (NAD+). Sirtuins act in different cellular
      compartments, such as the nucleus where they deacetylate histones and
      transcriptional factors, in the cytoplasm where they modulate cytoskeletal and
      signaling molecules, and in the mitochondria where they engage components of the
      metabolic machinery. Collectively, they tune metabolic processes to energy
      availability, and modulate stress responses, protein aggregation, inflammatory
      processes, and genome stability. As such, they have garnered much interest and
      have been widely studied in aging and age-related neurodegeneration. In this
      chapter, we review the identification of sirtuins and their biological targets.
      We focus on their biological mechanisms of action and how they might be
      regulated, including via NAD metabolism, transcriptional and posttranscriptional
      control, and as targets of pharmacological agents. Lastly, we highlight the
      numerous studies suggesting that sirtuins are efficacious therapeutic targets in
      neurodegenerative disease and injury.

PMID- 24037432
TI  - Perspectives on healthcare from the 2013 Edward J. Ill Excellence in Medicine
      Honorees.

PMID- 24037431
TI  - Jnk1 in murine hepatic stellate cells is a crucial mediator of liver
      fibrogenesis.
AB  - OBJECTIVE: The c-Jun N-terminal kinase-1 (Jnk1) gene has been shown to be
      involved in liver fibrosis. Here, we aimed to investigate the molecular mechanism
      and define the cell type involved in mediating the Jnk1-dependent effect on liver
      fibrogenesis. DESIGN: Jnk1(f/f) wildtype (WT), Jnk1(-/-) and Jnk1(Deltahepa)
      (hepatocyte-specific deletion of Jnk1) mice were subjected to (i) bile duct
      ligation (BDL) and (ii) CCl4-induced liver fibrosis. Additionally, we performed
      bone marrow transplantations (BMT), isolated primary hepatic stellate cells
      (HSCs), studied their activation in vitro and investigated human diseased liver
      samples. RESULTS: Phosphorylated Jnk was expressed in myofibroblasts, epithelial
      and inflammatory cells during the progression of fibrogenesis in humans and mice.
      In mice, liver transaminases, alkaline phosphatase, bilirubin and liver histology
      revealed reduced injury in Jnk1(-/-) compared with WT and Jnk1(Deltahepa) mice
      correlating with lower hepatocyte cell death and proliferation. Consequently,
      parameters of liver fibrosis such as Sirius red staining and collagen IA1 and
      alpha-smooth muscle actin expression were downregulated in Jnk1(-/-) compared
      with WT and Jnk1(Deltahepa) livers, 4 weeks after CCl4 or BDL. BMT experiments
      excluded bone marrow-derived cells from having a major impact on the Jnk1
      dependent effect on fibrogenesis, while primary HSCs from Jnk1(-/-) livers showed
      reduced transdifferentiation and extracellular matrix production. Moreover, Jnk1
      ablation caused a reduced lifespan and poor differentiation of HSCs into matrix
      producing myofibroblasts. CONCLUSIONS: Jnk1 in HSCs, but not in hepatocytes,
      significantly contribute to liver fibrosis development, identifying Jnk1 in HSCs
      as a profibrotic kinase and a promising cell-directed target for liver fibrosis.

PMID- 24037433
TI  - Minimally invasive surgery: the learning curve for physicians a discussion with
      Anthony C. Quartell, MD. Interview by Theresa Fay DiGeronimo.

PMID- 24037434
TI  - Having the conversation: empowering patients in end-of-life care decision making.

PMID- 24037435
TI  - Guardians of the gate: the Ellis Island hospitals and immigrant patients in the
      late 19th and early 20th centuries.

PMID- 24037436
TI  - Maintenance of certification as a condition of medical licensure: time for pause.

PMID- 24037437
TI  - Legislative brief: New Jersey legislatures address: ambulatory surgery centers.

PMID- 24037438
TI  - Edward J. Ill: a medical leader for all time.

PMID- 24037439
TI  - Travel-related health risks. Part 3: non-mosquito-borne infectious illnesses.

PMID- 24037440
TI  - Understanding the revolving door: individual and structural-level predictors of
      recidivism among individuals with HIV leaving jail.
AB  - Incarceration, particularly when recurrent, can significantly compromise the
      health of individuals living with HIV. Despite this, the occurrence of recidivism
      among individuals with HIV has been little examined, particularly among those
      leaving jail, who may be at especially high risk for return to the criminal
      justice system. We evaluated individual- and structural-level predictors of
      recidivism and time to re-incarceration in a cohort of 798 individuals with HIV
      leaving jail. Nearly a third of the sample experienced at least one re
      incarceration event in the 6 months following jail release. Having ever been
      diagnosed with a major psychiatric disorder, prior homelessness, having longer
      lifetime incarceration history, having been charged with a violent offense for
      the index incarceration and not having health insurance in the 30 days following
      jail release were predictive of recidivism and associated with shorter time to re
      incarceration. Health interventions for individuals with HIV who are involved in
      the criminal justice system should also target recidivism as a predisposing
      factor for poor health outcomes. The factors found to be associated with
      recidivism in this study may be potential targets for intervention and need to be
      further explored. Reducing criminal justice involvement should be a key component
      of efforts to promote more sustainable improvements in health and well-being
      among individuals living with HIV.

PMID- 24037441
TI  - Cyclic AMP-dependent protein kinase enhances SC35-promoted Tau exon 10 inclusion.
AB  - Alternative splicing of tau exon 10 generates tau with three or four microtubule
      binding repeats (3R-tau or 4R-tau). The ratio of 3R-tau to 4R-tau is
      approximately 1:1 in the adult normal human brain. Disturbances in the ratio
      result in neurodegenerative tauopathies. Splicing factor SC35 acts on a SC35-like
      element located at the 5' end of tau exon 10 and promotes tau exon 10 inclusion.
      Here, we report that protein kinase (PKA) was able to interact and phosphorylate
      SC35. Activation or overexpression of PKA catalytic subunits promoted SC35
      mediated tau exon 10 inclusion. Four PKA catalytic subunits, alpha1, alpha2,
      beta1, and beta2, all enhanced SC35-promoted tau exon 10 inclusion. SC35 has four
      putative PKA phosphorylation sites, Ser121, Ser128, Ser130, and Ser171.
      Pseudophosphorylation (SC354E) and blockage (SC354A) of phosphorylation of SC35
      at these four sites increased and decreased, respectively, SC35's ability to
      promote tau exon 10 inclusion. Moreover, PKA catalytic subunits no longer further
      enhanced tau exon 10 inclusion when these four were mutated to either alanine or
      glutamate. These results suggest that PKA interacts with and phosphorylates SC35
      and enhances SC35-promoted tau exon 10 inclusion. In Alzheimer's brain, down
      regulation of the PKA pathway could lead to dysregulation of tau exon 10,
      contributing to tau pathogenesis. 

PMID- 24037442
TI  - Health expenses and economic growth: convergence dynamics across the Indian
      States.
AB  - In this paper we explore convergence of real per capita output and health
      expenses across the Indian States. The new panel convergence methodology,
      developed by Phillips and Sul (Econometrica 75:1771-1855, 2007), is employed. The
      empirical findings suggest that these States form distinct convergent clubs,
      exhibiting considerable heterogeneity in the underlying growth and health
      expenses factors. These findings should help policy makers in designing
      appropriate growth-oriented and/or health sector programs and setting priorities
      in their implementation. 

PMID- 24037444
TI  - Bacterial pathogenesis: a sweet interaction with death for EPEC.

PMID- 24037443
TI  - Why does sleep stop migraine?
AB  - The relationship between sleep and migraine headaches is complex. Changes in
      sleep patterns can trigger migraine attacks, and sleep disorders may be
      associated with increased migraine frequency. Furthermore, migraine patients and
      their doctors very consistently report that sleep relieves already established
      migraine attacks. Herein we will try to answer the question, "Why does sleep stop
      migraine?" Since evidence for this relationship is largely based on empirical
      clinical observation, we will not provide a clinical review of the association.
      Instead, we will focus on the pathophysiology of migraine attacks and its
      intersections with sleep biology.

PMID- 24037450
TI  - Bacterial evolution: the road to E. faecium pathogenesis.

PMID- 24037453
TI  - Publication trends in Naunyn-Schmiedeberg's Archives of Pharmacology: focus on
      pharmacology in Egypt.
AB  - In a previous analysis of the country of origin of papers published in Naunyn
      Schmiedeberg's Archives of Pharmacology, a major shift toward contributions from
      emerging market countries, was noticed in comparison of 2010 to 2001
      publications. Repeating such analysis for 2012 publications in the journal
      confirmed this trend. An interesting new trend was the emerging presence of
      papers from a variety of Islamic countries including Egypt. Based on this trend,
      we shortly review the history and current structure of pharmacology in Egypt. It
      appears that the presence of Egyptian pharmacology in international journals
      including pharmacology journals has sharply been increasing over the last two
      decades. Challenges for a continuation of this encouraging trend are being
      discussed. 

PMID- 24037454
TI  - Factors affecting help seeking for mental health problems after deployment to
      Iraq and Afghanistan.
AB  - OBJECTIVE: This study assessed the prevalence of general medical problems, stress
      or emotional problems, and alcohol problems reported by members of the armed
      forces of the United Kingdom after deployment in Iraq or Afghanistan. The study
      also identified types of help seeking and factors associated with help seeking.
      METHODS: A total of 4,725 military personnel who were deployed to Iraq,
      Afghanistan, or both were asked about health problems attributable to the
      deployment and whether they had sought help for them. Data were collected through
      postal surveys between 2007 and 2009. Service and sociodemographic covariates and
      measures of current mental health, alcohol misuse, and functional impairment were
      included in the analyses. RESULTS: Of the 19% who reported stress or emotional
      problems, 42% sought help, most commonly medical help (29%). Of the 6% who
      reported alcohol problems, 31% sought help, most commonly medical help (17%).
      Medical help seeking for stress or emotional problems was associated with being
      female, holding a lower rank, having functional impairment, and meeting criteria
      for two or more mental health problems. Being divorced or separated was
      positively associated with nonmedical help seeking for stress or emotional
      problems. Help seeking for alcohol problems was associated with current mental
      disorders. CONCLUSIONS: Medical help seeking for stress or emotional problems was
      uncommon and was related to meeting criteria for two or more mental health
      problems. Commissioned officers were reluctant to seek medical help for stress or
      emotional problems. Help seeking for alcohol problems increased if personnel were
      experiencing additional mental health problems.

PMID- 24037451
TI  - Looking under the skin: the first steps in malarial infection and immunity.
AB  - Malaria, which is caused by Plasmodium spp., starts with an asymptomatic phase,
      during which sporozoites, the parasite form that is injected into the skin by a
      mosquito, develop into merozoites, the form that infects erythrocytes. This pre
      erythrocytic phase is still the most enigmatic in the parasite life cycle, but
      has long been recognized as an attractive vaccination target. In this Review, we
      present what has been learned in recent years about the natural history of the
      pre-erythrocytic stages, mainly using intravital imaging in rodents. We also
      consider how this new knowledge is in turn changing our understanding of the
      immune response mounted by the host against the pre-erythrocytic forms. 

PMID- 24037452
TI  - The legacy of Carl Woese and Wolfram Zillig: from phylogeny to landmark
      discoveries.
AB  - Two pioneers of twentieth century biology passed away during the past decade,
      Wolfram Zillig in April 2005 and Carl Woese in December 2012. Among several other
      accomplishments, Woese has been celebrated for the discovery of the domain
      Archaea and for establishing rRNA as the 'Rosetta Stone' of evolutionary and
      environmental microbiology. His work inspired many scientists in various fields
      of biology, and among them was Wolfram Zillig, who is credited with the discovery
      of several unique molecular features of archaea. In this Essay, we highlight the
      remarkable achievements of Woese and Zillig and consider how they have shaped the
      archaeal research landscape.

PMID- 24037455
TI  - Drug-induced liver injury after allogeneic bone marrow transplantation.
AB  - A 23-year-old woman developed acute severe hepatitis and jaundice on day 183
      after bone marrow transplantation from HLA-B antigen mismatched-related donor.
      The administration of prednisolone and cessation of the prescribed drugs resolved
      the liver injury. Drug lymphocyte stimulation test was positive for acyclovir,
      and liver biopsy indicated the characteristics of drug-induced liver injury
      (DILI) rather than graft-versus-host disease. Physicians should keep DILI in mind
      when considering differential diagnosis for liver complications after allogeneic
      cell transplantation. 

PMID- 24037456
TI  - Validation of a new proposed relapse risk score (CBC-score) for acute
      promyelocytic leukaemia.

PMID- 24037457
TI  - A comparative DFT study on aquation and nucleobase binding of ruthenium (II) and
      osmium (II) arene complexes.
AB  - The potential energy surfaces of the reactions of organometallic arene complexes
      of the type [(eta (6)-arene)M(II)(pic)Cl] (where pic = 2-picolinic acid, M = Ru
      or Os) were examined by a DFT computational study. Among the seven density
      functional methods, hybrid exchange functional B3LYP outperforms the others to
      explain the aquation of the complexes. The reactions and binding energies of
      Ru(II) and Os(II) arene complexes with both 9EtG and 9EtA were studied to gain
      insight into the reactivity of these types of organometallic complexes with DNA.
      The obtained data rationalize experimental observation, contributing to partly
      understanding the potential biological and medical applications of organometallic
      complexes.

PMID- 24037458
TI  - [Patients in the intensive care unit with valvular diseases].
AB  - Valvular dysfunction is as frequent as acute coronary syndromes in the
      pathogenesis of acute decompensated heart failure. The prevalence of relevant
      valvular dysfunction increases with age and reaches more than 10 % in patients
      over 75 years old. Guidelines and studies on the treatment of these patients,
      especially in an intensive care unit (ICU) setting are, however, scarce despite
      excellent guidelines for treatment of valvular heart disease in the general
      population. In the last decade a number of therapeutic alternatives became
      available when standard inotrope and vasopressor therapy fails to stabilize
      patients. These include balloon valvuloplasty in patients with severe aortic
      valve stenosis and assist devices, extracorporeal membrane oxygenation (ECMO) as
      well as mitral clipping. These therapeutic alternatives are to be considered as
      bridge to operation procedures in cases of shock due to valvular dysfunction, as
      hemodynamic stabilization and stabilization of organ function are essential to
      allow valve repair/replacement which is still considered to be the gold standard
      in this situation but is not always possible in the acute setting. 

PMID- 24037459
TI  - Barcelona consensus on supermicrosurgery.
AB  - The popularity of supermicrosurgery has increased dramatically over the past few
      years, but the lack of agreement regarding the name of the technique and its
      applications has caused misunderstandings among microsurgeons when trying to
      communicate and compare surgical procedures. We report the consensus reached on
      the name used to refer to supermicrosurgery techniques following the First
      European Conference on Supramicrosurgery held in Barcelona (Spain) on March 4-5,
      2010. Present applications, advantages, and disadvantages of supermicrosurgery
      are discussed. It was agreed that supermicrosurgery was the most accurate name to
      reflect the essence of this extremely delicate technique. According to Koshima,
      supermicrosurgery is a technique of microneurovascular anastomosis for vessels of
      0.3 to 0.8 mm and single nerve fascicles. The range of applications for this
      technique has increased rapidly and now includes lymphedema treatment, nerve
      reconstruction, replantation and reconstruction of amputated fingertips,
      microsurgical flap salvage, and new possibilities for free tissue transfer.
      Supermicrosurgery is a remarkably useful reconstructive tool that involves a
      great deal of skill and has a steep learning curve for the microsurgeon to
      master. Although it is currently performed by only a minority of microsurgeons,
      we consider it will be incorporated into conventional microsurgery in the near
      future.

PMID- 24037460
TI  - Attaching high charge density metal ions to surfaces and biomolecules. Reaction
      chemistry of hypodentate cobalt diamine complexes.
AB  - Hypodentate diamine cobalt(III) pentammine complexes
      [Co(NH3)5(NH2(CH2)(n)NH3)](ClO4)4 (8: a: n = 3; b: n = 4; c: n = 6; d: n = 8)
      have been synthesized via the reaction of [Co(NH3)5(OTf)](OTf)2 (TfOH = CF3SO3H)
      with the corresponding diamines. The analogous t-boc protected diamine complexes
      [Co(NH3)5(NH2(CH2)(n)NHt-boc)](ClO4)3 (7a-d) were prepared in 4-26% yield. Low
      yields for the formation of 7a-d are due to competing side reactions which also
      gave [Co(NH3)6](3+). Complexes 7a-d were deprotected using trifluoroacetic acid
      to give the corresponding hypodentate diamine complexes
      [Co(NH3)5(NH2(CH2)(n)NH3)](CF3CO2)0.5(ClO4)3.5 (9a-d). HBTU coupling of 8c with N
      (t-boc)-L-phenylalanine gave an amino acid functionalized cobalt pentammine
      complex [Co(NH3)5(NH2(CH2)6NHt-boc)-L-phenylalanine)](ClO4)3 (10). All new
      complexes were characterized using UV-vis and (1)H NMR spectroscopy, and
      elemental analysis. Grafting of 8c onto 2.4 mm poly(ethylene-co-acrylic acid)
      (PEAA) beads was achieved via amide coupling. Complex 8c was coupled to thioctic
      acid via amide coupling and the resulting cobalt disulfide complex [Co(NH3)5(N-(6
      aminohexyl)-5-(1,2-dithiolan-3-yl)pentanamide)](ClO4)3 (11) was attached to 10 nm
      Au nanoparticles. The amount of cobalt loading onto PEAA beads and Au
      nanoparticles was determined using ICP-MS and EDX.

PMID- 24037461
TI  - Investigation of lignin deposition on cellulose during hydrothermal pretreatment,
      its effect on cellulose hydrolysis, and underlying mechanisms.
AB  - In dilute acid pretreatment of lignocellulosic biomass, lignin has been shown to
      form droplets that deposit on the cellulose surface and retard enzymatic
      digestion of cellulose (Donohoe et al., 2008; Selig et al., 2007). However,
      studies of this nature are limited for hydrothermal pretreatment, with the result
      that the corresponding mechanisms that inhibit cellulosic enzymes are not well
      understood. In this study, scanning electron microscope (SEM) and wet chemical
      analysis of solids formed by hydrothermal pretreatment of a mixture of Avicel
      cellulose and poplar wood showed that lignin droplets from poplar wood relocated
      onto the Avicel surface. In addition, nuclear magnetic resonance (NMR) showed
      higher S/G ratios in deposited lignin than the initial lignin in poplar wood.
      Furthermore, the lignin droplets deposited on Avicel significantly impeded
      cellulose hydrolysis. A series of tests confirmed that blockage of the cellulose
      surface by lignin droplets was the main cause of cellulase inhibition. The
      results give new insights into the fate of lignin in hydrothermal pretreatment
      and its effects on enzymatic hydrolysis.

PMID- 24037462
TI  - "The angel of the house" in the realm of ART: feminist approach to oocyte and
      spare embryo donation for research.
AB  - The spectacular progress in assisted reproduction technology that has been
      witnessed for the past thirty years resulted in emerging new ethical dilemmas as
      well as the revision of some perennial ones. The paper aims at a feminist
      approach to oocyte and spare embryo donation for research. First, referring to
      different concepts of autonomy and informed consent, we discuss whether the
      decision to donate oocyte/embryo can truly be an autonomous choice of a female
      patient. Secondly, we argue the commonly adopted language of gift is misleading
      and that calling for altruism could put female patients at risk of exploitation.
      Finally, we point out that the presence of gender stereotypes in the procreative
      area casts doubt whether even a more robust notion of informed consent manages to
      overcome this risk. 

PMID- 24037463
TI  - Medical imaging informatics simulators: a tutorial.
AB  - PURPOSE: A medical imaging informatics infrastructure (MIII) platform is an
      organized method of selecting tools and synthesizing data from HIS/RIS/PACS/ePR
      systems with the aim of developing an imaging-based diagnosis or treatment
      system. Evaluation and analysis of these systems can be made more efficient by
      designing and implementing imaging informatics simulators. This tutorial
      introduces the MIII platform and provides the definition of treatment/diagnosis
      systems, while primarily focusing on the development of the related simulators.
      METHODS: A medical imaging informatics (MII) simulator in this context is defined
      as a system integration of many selected imaging and data components from the
      MIII platform and clinical treatment protocols, which can be used to simulate
      patient workflow and data flow starting from diagnostic procedures to the
      completion of treatment. In these processes, DICOM and HL-7 standards, IHE
      workflow profiles, and Web-based tools are emphasized. From the information
      collected in the database of a specific simulator, evidence-based medicine can be
      hypothesized to choose and integrate optimal clinical decision support
      components. Other relevant, selected clinical resources in addition to data and
      tools from the HIS/RIS/PACS and ePRs platform may also be tailored to develop the
      simulator. These resources can include image content indexing, 3D rendering with
      visualization, data grid and cloud computing, computer-aided diagnosis (CAD)
      methods, specialized image-assisted surgical, and radiation therapy technologies.
      RESULTS: Five simulators will be discussed in this tutorial. The PACS-ePR
      simulator with image distribution is the cradle of the other simulators. It
      supplies the necessary PACS-based ingredients and data security for the
      development of four other simulators: the data grid simulator for molecular
      imaging, CAD-PACS, radiation therapy simulator, and image-assisted surgery
      simulator. The purpose and benefits of each simulator with respect to its
      clinical relevance are presented. CONCLUSION: The concept, design, and
      development of these five simulators have been implemented in laboratory settings
      for education and training. Some of them have been extended to clinical
      applications in hospital environments.

PMID- 24037464
TI  - Expert's comment concerning Grand Rounds case entitled "total spondylectomy for
      solitary bone plasmacytoma of the lumbar spine in a young woman. A case report
      and review of the literature" (by N. von der Hoeh, S.K. Tschoeke, J. Gulow, A.
      Voelker, U. Siebolts and C.-E. Heyde).

PMID- 24037465
TI  - Answer to the Letter to the Editor of Mingbo Tian et al. concerning "Body mass
      index and risk of surgical site infection following spine surgery: a meta
      analysis" by D.Y. Abdallah, M.M. Jadaan and J.P. McCabe; Eur Spine J,
      doi:10.1007/s00586-013-2890-6.

PMID- 24037466
TI  - Models for palliative care in sub-Saharan Africa.

PMID- 24037467
TI  - Global application of therapeutic hypothermia to treat perinatal asphyxial
      encephalopathy.
AB  - Therapeutic hypothermia improves neurodevelopmental outcome following perinatal
      asphyxial encephalopathy and has now become 'standard of care' in industrialised
      countries. However, none of the cooling trials so far have been conducted in
      developing countries, where approximately one million asphyxial deaths occur
      every year. Use of therapeutic hypothermia in such settings raises several
      clinical, pragmatic and ethical issues. We suggest that rigorous clinical trials
      of cooling are required to ensure that a safe and effective neuroprotective
      therapy demonstrated in high resource settings does not become an unsafe and
      ineffective practice in low resource settings. 

PMID- 24037468
TI  - Achieving large ends with limited means: grand strategy in global health.
AB  - Unprecedented attention is focused on global health, with a four-fold increase in
      development assistance in the last 15 years and the scope of global health
      expanding beyond infectious disease to include chronic disease and health systems
      strengthening. As the global impact of health is more widely understood, it has
      become a crucial element of international relations, economic development, and
      foreign affairs. At this potential leverage point in the global health movement,
      the application of grand strategy is of critical importance. Grand strategy,
      i.e., the development and implementation of comprehensive plans of action to
      achieve large ends with limited means, has been refined through centuries of
      international relations and the management of states but has been inadequately
      applied to global health policy and implementation. We review key principles of
      grand strategy and demonstrate their applicability to a central global health
      issue: maternal mortality. The principles include: start with the end in mind,
      take an ecological approach, recognize that tactics matter, use positive deviance
      to characterize practical solutions and foster scale-up, and integrate timely
      intelligence and data into health interventions and improvement efforts. We
      advocate for the greater use of grand strategy in global health. 

PMID- 24037469
TI  - Risk factors for mortality in AIDS-associated Kaposi sarcoma in a primary care
      antiretroviral treatment program in Malawi.
AB  - AIDS-associated Kaposi sarcoma (AIDS-KS) is the most common HIV-related
      malignancy. The majority of cases are found in sub-Saharan Africa. This
      retrospective cohort study describes characteristics of patients with AIDS-KS and
      factors associated with mortality in an antiretroviral treatment (ART) program in
      rural Malawi. Of 11 122 patients enrolled on ART, 830 (7%) had AIDS-KS. Patients
      with AIDS-KS were more likely to be lost to follow-up (22% versus 14%, P < 0.001)
      and showed a higher mortality (22% versus 10%, P < 0.001) compared to patients
      without AIDS-KS. A CD4 count <=150 cells/MUl, advanced stage AIDS-KS, and absence
      of bleomycin chemotherapy were associated with increased mortality. Earlier
      diagnosis and improved treatment of AIDS-KS are urgently needed in order to
      reduce mortality. 

PMID- 24037470
TI  - The role of Product Development Partnerships in research and development for
      neglected diseases.
AB  - Product Development Partnerships (PDPs) are playing an increasingly important
      role in the development of new medicines for neglected diseases of the developing
      world; however, there has been limited information on their funding and
      expenditure patterns. This paper analyses funding for the 14 PDPs working on
      neglected disease research and development (R&D) by using unpublished data from
      the Global Funding of Innovation for Neglected Diseases (G-FINDER) project, which
      surveyed 2007 global investments into R&D of products for neglected diseases.
      PDPs captured US$469 million or 23% of 'external' R&D funding for neglected
      diseases, i.e. funding granted by donors to research organisations, as opposed to
      internal investments by donors. PDP's funding sources were highly concentrated
      with the Gates Foundation providing nearly half of PDPs' combined income (49%)
      and four public funders (the US Agency for International Development (USAID), the
      UK Department for International Development (DFID), the Dutch government and
      Irish Aid) providing 28%. PDPs collectively spent US$262 million on R&D
      activities in 2007, with 88% of this expenditure going to academic institutions,
      contract research organisations and companies in the developed world. Our
      analysis confirms the central role played by PDPs in R&D for neglected diseases,
      but highlights the need to diversify their funding sources. 

PMID- 24037471
TI  - Malaria notifications in the Australian Defence Force from 1998 to 2007.
AB  - We report here a retrospective analysis of all malaria cases in military
      personnel reported to the Australian Defence Force (ADF) Central Malaria Register
      from 1998 to 2007. A total of 637 cases of malaria were notified affecting 487
      individuals. Of these 85.9% (547) were infected with Plasmodium vivax malaria and
      10.2% (65) with P. falciparum malaria. The majority of cases were from Timor
      Leste (78.5%, 501/637). Malaria attack rates of 0.9% (369/40 571), 1.1% (52/4776)
      and 0.4% (20/5345) were seen in Timor Leste, Bougainville and the Solomon
      Islands, respectively. The median period following departure from a malarious
      country to presentation of P. falciparum was 17 d (range 1-47 d) and for a
      primary presentation of P. vivax malaria was 86 d (range 1-505 d). Increasing the
      dose of primaquine from 22.5 mg daily to 30 mg daily for 14 d for radical cure of
      P. vivax malaria reduced the failure rate from 46.6% (35/75) to 9.4% (17/181) in
      subjects returning from Timor Leste. Malaria remains a serious problem for ADF
      soldiers deploying to malarious areas, particularly the incidence of relapsing
      vivax malaria and the tolerance of these vivax strains to primaquine. 

PMID- 24037472
TI  - Householder perspectives and preferences on water storage and use, with reference
      to dengue, in the Mekong Delta, southern Vietnam.
AB  - Community-based perceptions and behaviour around water source preference,
      household water storage patterns and water use, and householders' knowledge and
      behaviour with respect to dengue etiology and transmission, were examined in
      three communes located in the Mekong Delta area in southern Vietnam. Through
      focus group discussions, most participants identified poorly screened or
      uncovered water containers (including household water storage containers and
      other types of artificial containers) as habitats for mosquitoes that transmit
      dengue viruses, and thereby demonstrated a clear understanding of the links
      between household water storage practices and the threat of dengue. Our
      qualitative analyses also revealed broader community-based concerns about the
      limited availability of water and strong preferences for storage of rainwater
      based upon perceptions of cost, quality and security of supply. These perceptions
      are central to shaping householders' responses to water infrastructure projects.
      The limited availability of water during the dry season and insufficient numbers
      of water storage containers are over-riding community concerns which provide an
      important context to understanding community behaviours and responses to public
      health interventions against dengue. Such concerns are important precursors to
      selecting the type of intervention. 

PMID- 24037473
TI  - A geographic analysis of access to health services in rural Guatemala.
AB  - This paper uses road network analysis to quantify access to health care services
      in Alta Verapaz, a rural district in Guatemala with a majority Mayan population.
      Population data from the 2002 Guatemalan census, the location of health care
      facilities from the Ministry of Public Health and Social Assistance, and road and
      trail locations from the National Geographic Institute were included in a
      geographic information system (GIS). We computed the shortest path from each
      populated place to the nearest health care facility and then estimated the
      approximate travel time to the health facility based on road surface type. Road
      network analysis found that approximately 38.1% of residents of Alta Verapaz live
      within one hour of a hospital and 76.8% live within one hour of a basic care
      facility. In comparison, a circular buffer method found that 27.5% had access to
      a hospital and 94.5% had access to a primary care facility. Poverty was
      correlated with reduced access to care. The use of models that adjust for road
      types and allow for accurate estimation of travel times are helpful tools to
      identifying populations with limited access to health care services. 

PMID- 24037474
TI  - Analysis of the perception of institutional function for health sector reform in
      Nigeria.
AB  - Institutional function reflects the institution's understanding of the world
      around it, its ability to locate itself within that world and to make decisions
      in relation to it. Three dimensions of institutional function were identified as
      management, environmental mastery and service delivery. This study analysed the
      perception of institutional function of four hospitals in Nigeria by 507
      healthcare professionals and managers and its influence on the implementation of
      the health sector reform programme in the country. The respondents were doctors
      and dentists (30%), nurses (27.2%), pharmacists (8.9%), managers (15.5%) and
      other allied healthcare workers (18.4%). The overall perception of institutional
      function was 56.3%. The perceptions of the three dimensions of institutional
      function were management 52.7%, environmental mastery 50.8% and service delivery
      62.6%. Three out of 12 statements on institutional function had levels of
      perception that were lower than 50%. These were adequacy of management skills
      (49.7%), functioning management information systems that are used in management
      decision-making (47.9%) and degree of autonomy for the hospitals (42.4%). There
      is the need to strengthen the institutional function of Nigerian hospitals,
      especially the acquisition of management skills by the healthcare professionals
      and managers, management information systems and autonomy for the hospitals. 

PMID- 24037475
TI  - Prevalence of rubella IgG antibodies among pregnant women in Zaria, Nigeria.
AB  - Rubella is a vaccine-preventable viral infection which in pregnancy can lead to
      foetal wastage and congenital malformations. A rubella IgG serosurvey of 430
      consenting pregnant women attending the antenatal clinic was conducted at the
      Ahmadu Bello University Teaching Hospital, Zaria between 1 May 2007 and 29
      February 2008. Questionnaires were also used to assess their level of awareness
      and pregnancy outcomes noted. Of the 430 serum samples tested, 421 (97.9%) were
      positive and 9 (2.1%) were negative for rubella IgG antibody. Differences in
      sociodemographic factors were of little significance between the groups and
      awareness of the infection was low. This high prevalence suggests that a
      sustained viral circulation exists in children and infection occurs early in
      infancy hence a high level of immunity exists in pregnant women with low levels
      of complications. In the absence of mass vaccination, all seronegative women
      should be vaccinated after delivery. 

PMID- 24037476
TI  - Body temperature changes of newborns under fluorescent versus LED phototherapy.
AB  - OBJECTIVE: To determine changes in body temperature (BT) of hyperbilirubinemic
      newborns under conventional phototherapy with fluorescent lamps and light
      emitting diodes (LED) at different irradiances. METHODS: Otherwise healthy
      newborn infants >34 wk gestational age (GA) hospitalized for indirect
      hyperbilirubinemia, requiring phototherapy in the first 10 d of life were
      enrolled. Infants who received conventional phototherapy with fluorescent lamps
      (10-15 MUW/cm(2)/nm irradiance) were defined as group 1, LED phototherapy of 26
      60 MUW/cm(2)/nm irradiance as group 2, and LED phototherapy of 60-120
      MUW/cm(2)/nm irradiance as group 3. Primary outcome measure was mean BT which was
      defined as arithmetical mean of axillary BT measured at 2 h intervals during the
      first day of phototherapy. RESULTS: Thirty patients were enroled in each group.
      Mean birth weight and GA of the total cohort was 2800 +/- 530 g and 36.6 +/- 2
      wk, respectively. Baseline demographic variables and serum total bilirubin levels
      were similar among groups. Mean BT was 36.7 +/- 0.1  degrees C in group 1, 36.6
      +/- 0.2  degrees C in group 2, 37.7 +/- 0.2  degrees C in group 3. Mean BT was
      higher in group 3 compared to group 1 (p < 0.001) and group 2 (p < 0.001). Group
      1 and group 2 had similar mean BT measurements (p = 0.09). During phototherapy
      all the patients in group 3 had at least one BT measurement >= 37.5  degrees C
      and 77 % had BT >= 38  degrees C. Only one patient in group 2 had BT >= 37.5 
      degrees C which was also >= 38  degrees C. During phototherapy all BT
      measurements were <37.5  degrees C in group 1. CONCLUSIONS: LED phototherapy of
      >= 60 MUW/cm(2)/nm intensity significantly increases BT in hyperbilirubinemic
      newborns.

PMID- 24037477
TI  - Newborn screening for sickle cell disease in India: the need for defining optimal
      clinical care.

PMID- 24037478
TI  - Delayed Vitamin K deficiency related bleeding: is it genetically linked?

PMID- 24037479
TI  - Enteric fever in children below 2 y--need for an effective conjugate vaccine?

PMID- 24037480
TI  - Stability of human telomere quadruplexes at high DNA concentrations.
AB  - For mimicking macromolecular crowding of DNA quadruplexes, various crowding
      agents have been used, typically PEG, with quadruplexes of micromolar strand
      concentrations. Thermal and thermodynamic stabilities of these quadruplexes
      increased with the concentration of the agents, the rise depended on the crowder
      used. A different phenomenon was observed, and is presented in this article, when
      the crowder was the quadruplex itself. With DNA strand concentrations ranging
      from 3 uM to 9 mM, the thermostability did not change up to ~2 mM, above which it
      increased, indicating that the unfolding quadruplex units were not monomolecular
      above ~2 mM. The results are explained by self-association of the G-quadruplexes
      above this concentration. The DeltaG( degrees ) 37 values, evaluated only below 2
      mM, did not become more negative, as with the non-DNA crowders, instead, slightly
      increased. Folding topology changed from antiparallel to hybrid above 2 mM, and
      then to parallel quadruplexes at high, 6-9 mM strand concentrations. In this
      range, the concentration of the DNA phosphate anions approached the concentration
      of the K(+) counterions used. Volume exclusion is assumed to promote the
      topological changes of quadruplexes toward the parallel, and the decreased
      screening of anions could affect their stability.

PMID- 24037481
TI  - Bacillus sediminis sp. nov., isolated from an electroactive biofilm.
AB  - A Gram-stain positive, facultative anaerobic, motile, spore-forming rod-shaped
      bacterium with peritrichous flagella, designated DX-5(T), was isolated from an
      electroactive biofilm. Growth was observed to occur at 35-60  degrees C, at pH
      7.0-10.0 and with 0.5-10 % (w/v) NaCl (optimum growth: 50  degrees C, pH 8.0 and
      0.5-3 % NaCl). Cells were determined to be catalase- and oxidase-positive. The
      predominant respiratory quinone was identified as MK-7; the major polar lipids
      were determined to be diphosphatidylglycerol, phosphatidylglycerol, glycolipid,
      aminoglycolipid and an unidentified phospholipid; the DNA G+C content was
      determined to be 46.6 mol%; and the major fatty acids (>5 %) were identified as
      anteiso-C15:0 (33.6 %), iso-C15:0 (24.1 %) and anteiso-C17:0 (13.4 %). The
      phylogenetic analysis based on 16S rRNA gene sequence comparisons indicated that
      strain DX-5(T) should be assigned to the genus Bacillus, and was related most
      closely to the type strains of B. fortis DSM 16012(T) (96.3 %), B. composti KACC
      16872(T) (96.3 %) and B. fordii DSM 16014(T) (95.8 %). Results of phenotypic,
      chemotaxonomic and genotypic analysis indicated that strain DX-5(T) represents a
      novel species, for which the name B. sediminis sp. nov. is proposed. The type
      strain is DX-5(T) (=CGMCC 1.12412(T) = KCTC 33102(T)).

PMID- 24037482
TI  - Streptomyces muensis sp. nov.
AB  - A strain of Streptomyces, MBRL 179(T), isolated from a sample from a Limestone
      quarry located at Hundung, Manipur, India, was characterized by polyphasic
      taxonomy. The strain formed a monophyletic clade with Streptomyces
      spinoverrucosus NBRC 14228(T) (16S rRNA gene sequence similarity of 99.3 %) in
      the Neighbour-joining tree. DNA-DNA hybridization experiment gave a DNA-DNA
      relatedness value of 34.7 % between MBRL 179(T) and S. spinoverrucosus NBRC
      14228(T). Strain MBRL 179(T) contained LL-diaminopimelic acid, xylose, glucose,
      and mannose in the whole cell-wall hydrolysates along with small amount of
      ribose. The major polar lipids detected were diphosphatidylglycerol,
      phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and
      phosphatidylinositolmannoside, with other unknown phospholipids and
      aminophospholipid. MK-9(H6), MK-9(H8) and MK-9(H4) were the predominant
      menaquinones detected. The major fatty acids were anteiso-C16:0 (28.1 %), iso
      C16:0 (20.3 %), C16:0 (9.4 %) and anteiso-C17:0 (8.3 %). The G+C content of the
      genomic DNA was 71.1 %. Based on the polyphasic experiment results, the strain
      MBRL 179(T) merits recognition as a representative of a novel species of the
      genus Streptomyces for which the name Streptomyces muensis sp. nov. is proposed;
      the type strain is MBRL 179(T) (=JCM 17576(T) = KCTC 29124(T)).

PMID- 24037483
TI  - Abstracts of the 41st Congress of the German Society for Rheumatology. September
      18-21, 2013. Heidelberg/Mannheim, Germany.

PMID- 24037484
TI  - Patellotibial contusions in anterior cruciate ligament tears.
AB  - Bone contusions are an important ancillary finding of many knee injuries. Not
      only are they a source of pain, they may suggest a mechanism of injury or a
      specific derangement of the knee joint. We have encountered a small number of
      patients being evaluated for anterior cruciate ligament (ACL) tears with
      unexplained patellar and tibial edema at magnetic resonance (MR) imaging. We
      present three individuals with contusions of the inferior patella with a
      corresponding contusion of the anteromedial tibial plateau. Internal derangements
      in these patients were similar to other individuals with acute ACL tears, however
      osseous contusions were more widespread. In conclusion, patellotibial contusions
      are rare and may indicate an injury with forces greater than usually encountered
      in most ACL tears. A careful search for uncommon associated injuries is prudent
      in these high-energy knee injuries. 

PMID- 24037486
TI  - Small molecule targeted therapies for the second-line treatment for metastatic
      renal cell carcinoma: a systematic review and indirect comparison of safety and
      efficacy.
AB  - BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) and a good
      performance status typically receive an anti-vascular endothelial growth factor
      receptor (VEGFR) TKI (sunitinib or pazopanib) as initial therapy. Upon disease
      progression or intolerance, there are four orally administered agents approved in
      the second-line setting (including cytokine-refractory). However, head-to-head
      comparative trial data are limited. In this study, an indirect statistical
      comparison of safety and efficacy was undertaken between axitinib, sorafenib,
      pazopanib and everolimus in second-line therapy mRCC. METHODS: A systematic
      review of major databases was conducted from January 2005 to June 2013 for
      randomized controlled trials (RCTs) evaluating at least one of the four agents in
      second-line mRCC. Bayesian mixed treatment comparison models were fitted to
      assess relative effectiveness on multiple endpoints such as objective response
      rates, dose-limiting grade III/IV toxicities, treatment discontinuations and
      progression-free survival (PFS). RESULTS: Four RCTs met the inclusion criteria.
      All four agents seem able to induce tumor shrinkage and to provide patients with
      a clinically meaningful PFS benefit. Axitinib was superior to pazopanib [hazard
      ratio (HR) 0.64; 95 % credible interval (95 % Crl) 0.42-0.96] and sorafenib (HR
      0.70; 95 % Crl 0.57-0.87) in terms of PFS. However, axitinib was associated with
      an elevated risk of fatigue and to a lesser extent stomatitis. CONCLUSIONS:
      Keeping in mind the caveats associated with cross-trial statistical comparisons,
      axitinib provides superior PFS relative to pazopanib and sorafenib. Everolimus,
      an mammalian target of rapamycin inhibitor, is mechanistically distinct from the
      other agents and remains a useful option for patient's post-anti-VEGFR TKI
      failure.

PMID- 24037487
TI  - Receptor change-clinicopathologic analysis of matched pairs of primary and
      cerebral metastatic breast cancer.
AB  - OBJECTIVE: A challenge in the management of breast cancer is development of brain
      metastases (BM) with limited survival. In primary breast cancer, ER/PR/HER2 are
      important prognostic markers and are important for making effective treatment
      decisions. Changes in immunohistochemical markers of metastases are with unclear
      clinical significance, and mechanisms of resistance to endocrine therapy are an
      additional challenge. The aim of this retrospective study is to detect changes in
      immunohistochemical markers of primary and BM and to recognize if receptor change
      has prognostic impact. METHODS: Twenty-four consecutive primary breast cancer
      patients who developed BM and got surgical resection of BM were enrolled. Matched
      pair analyses of primary and BM were done with evaluation by immunostaining
      (ER/PR/HER2). RESULTS: A small tumor size, ductal histology and HER2+ tumors were
      associated with BM. Loss of ER/PR receptor positivity was observed in BM compared
      to primary (ER: 50.0 %/22.7 %; p = 0.004; PR: 45.8 %/9.1 %; p = n.s),
      respectively, and almost no change in HER2 status (>80 %; p = 0.012). Patients
      with ER-/PR-negative or HER2-positive primary had shorter time to recurrence than
      ER-/PR-positive and HER2-negative patients. Receptor change has negative
      prognostic impact. CONCLUSION: With the observed loss of receptor positivity,
      therapeutic options are diminished. Identification of patients with a high risk
      for BM is warranted to evaluate preventive strategies.

PMID- 24037488
TI  - Intensity-modulated adjuvant whole breast radiation delivered with static angle
      tomotherapy (TomoDirect): a prospective case series.
AB  - PURPOSE: To report the 2-year outcomes of whole breast intensity-modulated
      radiotherapy (IMRT) after conserving surgery for early breast cancer (EBC)
      delivered with static angle tomotherapy (TomoDirect) (TD). METHODS: A prospective
      cohort of 120 EBC patients underwent whole breast IMRT with TD between 2010 and
      2012. Radiation was delivered to a conventionally fractionated whole breast total
      dose of 50 Gy with TD, followed by a sequential conventionally fractionated tumor
      bed boost dose of 10-16 Gy with helical tomotherapy (HT). Clinical endpoints
      include acute and late toxicity, cosmesis, quality of life and local control.
      RESULTS: Median follow-up was 24 months (range 12-36 months); maximum detected
      acute skin toxicity was G0 22 %; G1 63 %; G2 12 % and G3 3 %. Predictors of acute
      dermatitis were as follows: volume of the whole breast minus boost volume
      receiving 105, 110 and 115 % of prescription dose, whole breast and boost volume,
      breast thickness and soft tissue thickness. Late skin toxicity was mild with no
      >G2 events. Cosmesis was good/excellent in 91.7 % of patients and fair/poor in
      8.3 %. Quality of life was preserved over time, but for fatigue, transiently
      increased. CONCLUSION: Adjuvant whole breast IMRT delivered sequentially with
      both TD and HT provides consistent clinical results. An observed unintended
      excessive dose outside the tumor bed might increase acute toxicity and eventually
      affect long-term clinical endpoints. The incorporation of the boost dose within
      the whole breast phase employing a simultaneous integrated boost (SIB) approach
      might mitigate this issue.

PMID- 24037490
TI  - Does healthcare financing converge? Evidence from eight OECD countries.
AB  - This study investigated the convergence of healthcare financing across eight OECD
      countries during 1960-2009 for the first time. The panel stationary test
      incorporating both shapes of multiple structural breaks (i.e., sharp drifts and
      smooth transition shifts) and cross-sectional dependence was used to provide
      reliable evidence of convergence in healthcare financing. Our results suggested
      that the public share of total healthcare financing in eight OECD countries has
      exhibited signs of convergence towards that of the US. The convergence of
      healthcare financing not only reflected a decline in the share of public
      healthcare financing in these eight OECD countries but also exhibited an upward
      trend in the share of public healthcare financing in the US over the period of
      1960-2009. 

PMID- 24037491
TI  - Natural Antibodies Against Sialoglycans.
AB  - Natural antibodies, part of the innate immunity system, are produced at strictly
      regulated levels in normal sera without immunization and thus are part of the
      innate immune system. The best studied natural antibodies are those directed
      against blood group antigens A and B and xeno-antigens including
      glycolylneuraminic acid containing Hanganutziu-Deicher (HD) glycolipid. Abnormal
      levels of anti-glycan antibodies were found in a number of pathologies. In many
      cases pathological antibodies are known to bind gangliosides. The genesis of anti
      glycan antibodies in healthy humans and the reasons for their changes in
      pathologies are poorly understood. With a growing interest in their diagnostic
      applications, it is important to determine the carbohydrate structures that are
      recognized by antibodies present in the circulation of healthy individuals. We
      tested a large number of healthy donors using a printed glycan array (PGA) in a
      microchip format. The PGA contained ~300 glycans, representing mostly normal
      mammalian structures of glycoproteins and glycolipids, and many of the structures
      presented are biologically relevant sialylated motifs. As revealed by PGA, the
      sera interacted with at least 70 normal human glycans. With only few exceptions,
      antibodies recognizing sialosides have not been identified. Moderate levels of
      antibodies and moderate variability were observed in the case of SiaT n and its
      glycolyl variant. Unexpectedly, we found minimal antibody titer directed against
      Neu5Gcalpha and the trisaccharide Neu5Gcalpha2-6Galbeta1-4GlcNAc, although this
      form of neuraminic acid does not occur naturally in humans. Antibodies
      recognizing sialosides in unnatural beta-configuration have been detected and
      confirmed Springer's paradigm that circulating antibodies represent a reaction
      against bacteria. Gram-negative bacteria contain LPS with betaKDN and/or betaKDO
      which are very close analogs of Neu5Ac that are found in beta-connected form.
      Antibodies against the biantennary N-glycan chain, (Neu5Acalpha2-6Galbeta1
      4GlcNAcbeta1-2Manalpha)2-3,6-Manbeta1-4GlcNAcbeta1-4GlcNAc were never observed
      and similarly we never saw antibodies directed against the SiaLe(a)/SiaLe (x)
      motifs. Anti-sialoglycan antibodies can be masked with gangliosides: for example,
      we observe about a five times higher level of anti-GD3 in purified total IgG
      compared to the same concentration of total Ig in the composition of native
      serum. For several antibodies we observed anomalous binding in diluted sera,
      namely, the signals towards sialylated glycans were increased in the PGA if
      diluted sera were used. 

PMID- 24037489
TI  - Effects of psycho-behavioral interventions on immune functioning in cancer
      patients: a systematic review.
AB  - PURPOSE: This study aimed at summarizing evidence about effects of psycho
      behavioral interventions (PBIs) on immune responses among cancer patients and
      analyzing quality of published studies so as to inform future researches.
      METHODS: Literature retrieval utilized both highly inclusive algorithms searching
      randomized controlled studies published in English and Chinese and manual
      searching of eligible studies from references of relevant review papers. Two
      researchers examined the articles selected separately and extracted the
      information using a pre-designed form for soliciting data about the trials (e.g.,
      sample size, disease status, intervention, immune responses) and quality ratings
      of the studies. Both narrative descriptions and meta-analysis (via Review manager
      5) were used synthesizing the effects of PBIs on immune responses among cancer
      patients and state of art of the researches in this area. RESULTS: Seventy-six
      RCTs met inclusion criteria. PBIs implemented were divided into three major
      categories including psychological state adjustment, physical activity and
      dietary modification. Immune indicators measured included CD4+ cells, CD8+ cells,
      CD4/CDC8+ ratio, CD3+ cells, NK cell activity, etc. Effects of PBIs on immune
      responses documented in individual papers were mixed and pooled analysis of CD4+
      cells, CD4+/CD8+ ratio, CD3+ cells, NKCA, IgG, IgM and IL-2 showed modest
      effects. However, there were huge discrepancies in intervention effects between
      studies published in English and Chinese and the results should be interpreted
      with caution. Besides, most studies suffer from some quality flaws concerning
      blinding, randomization procedures, compliance, attrition and intention-to-treat
      analyses, etc. CONCLUSIONS: Although there are considerable evidences of PBI
      effects on some immune indicators, the effect sizes are modest and it is still
      premature to conclude whether PBIs have effects on immune functions among cancer
      patients. There is a clear need for much more rigorous efforts in this area and
      future researches should pay particular attention to intervention dose and focus,
      sample size and comparable immune measures.

PMID- 24037492
TI  - Do abdominal cutouts in thoracolumbosacral orthoses increase pulmonary function?
AB  - BACKGROUND: Thoracolumbosacral orthoses (TLSOs) are effective in their intended
      purpose of limiting spinal movement but tend to restrict rib cage and abdominal
      motion. Incorporating an abdominal cutout, allowing abdominal excursion, may
      reduce the restraint on abdominal expansion associated with inhalation and
      thereby reduce pulmonary compromise. QUESTIONS/PURPOSES: (1) For healthy adults,
      does a TLSO restrict pulmonary function at rest and after exercise compared with
      no TLSO (control)? (2) At rest, is pulmonary function increased by adding an
      abdominal cutout to the TLSO (open) compared with a traditional closed TLSO (no
      abdominal cutout)? (3) Are those results similar after exercise? METHODS: Twenty
      healthy adults wore a custom-molded TLSO with a reattachable abdominal cutout.
      Forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were
      recorded at rest and after exercise in three conditions: (1) no TLSO (control);
      (2) TLSO (closed); and (3) TLSO (open). RESULTS: Wearing a TLSO (closed or open)
      reduced FVC and FEV1 similarly at rest (p < 0.001) and after exercise (p < 0.001)
      compared with controls. Adding an abdominal cutout (open) to the TLSO increased
      FVC at rest (95% confidence interval [CI], 3.79-4.76; p = 0.007) and postexercise
      (95% CI, 3.80-4.73; p = 0.025) compared with the closed TLSO, and FEV1 increased
      postexercise (95% CI, 3.01-3.76; p = 0.02) but not at rest (95% CI, 2.96-3.73; p
      = 0.053). CONCLUSIONS: TLSOs restrict pulmonary function in healthy adults. An
      abdominal cutout in the TLSO increased pulmonary function, especially with
      activity, suggesting that cutouts should be considered when fabricating TLSOs for
      individuals with compromised breathing such as with neuromuscular disorders,
      scoliosis, or spine surgery.

PMID- 24037494
TI  - Iodopovidone pleurodesis for isolated pulmonary Langerhan's cell histiocytosis in
      a two year old child.
AB  - Isolated pulmonary involvement in Langerhans Cell Histiocytosis (LCH) is rare in
      childhood. The authors report a 2-y-old boy who presented with acute history of
      fever, cough and respiratory distress; later developed pneumothorax; whose CT
      thorax showed diffuse pulmonary cystic lucencies bilaterally. Lung biopsy
      confirmed pulmonary LCH with CD1a positivity. Recurrent spontaneous
      pneumothoraces are common in patients of pulmonary LCH; which necessitates rapid
      intervention. The authors share their experience of successfully using
      iodopovidone in pleurodesis for repeated pneumothorax episodes in this child with
      rare diagnosis of isolated pulmonary LCH. 

PMID- 24037493
TI  - Effects of the fatty acid amide hydrolase inhibitor URB597 on coping behavior
      under challenging conditions in mice.
AB  - RATIONALE: Recent evidence suggests that in addition to controlling emotional
      behavior in general, endocannabinoid signaling is engaged in shaping behavioral
      responses to challenges. This important function of endocannabinoids is still
      poorly understood. OBJECTIVES: Here we investigated the impact of blockade of
      fatty acid amide hydrolase (FAAH), the degrading enzyme of anandamide on
      behavioral responses induced by challenges of different intensity. METHODS: Mice
      treated with FAAH inhibitor URB597 were either manually restrained on their backs
      (back test) or received foot-shocks. RESULTS: The behavior of mice showed bimodal
      distribution in the back test: they either predominantly showed escape attempts
      or equally distributed time between passivity and escape. URB597 increased
      escapes in animals with low escape scores. No effects were noticed in mice
      showing high escape scores, which is likely due to a ceiling effect. We
      hypothesized that stronger stressors would wash out individual differences in
      coping; therefore, we exposed mice to foot-shocks that decreased locomotion and
      increased freezing in all mice. URB597 ameliorated both responses. The re
      exposure of mice to the shock cage 14 days later without delivering shocks or
      treatment was followed by reduced and fragmented sleep as shown by
      electrophysiological recordings. Surprisingly, sleep was more disturbed after the
      reminder than after shocks in rats receiving vehicle before foot-shocks. These
      reminder-induced disturbances were abolished by URB597 administered before
      shocks. CONCLUSIONS: These findings suggest that FAAH blockade has an important
      role in the selection of behavioral responses under challenging conditions and
      judging from its long-term effects-that it influences the cognitive appraisal of
      the challenge.

PMID- 24037495
TI  - L-2-hydroxyglutaric aciduria: report of two Indian families.
AB  - L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare type of organic acidemia that
      has characteristic neurological manifestations including macrocephaly,
      developmental delay, epilepsy and cerebellar ataxia. Worldwide, few hundred cases
      of L-2-HGA are reported till date. The authors report the first three cases of L
      2-HGA from two Indian families. Pertinent clinical aspects of this rare
      neurometabolic disorder namely, lack of acute exacerbations, and predisposition
      to brain tumors, are highlighted. In the present series, all cases had infantile
      onset of symptoms in the form of global developmental delay, seizures and
      cerebellar ataxia without extra-pyramidal signs or macrocephaly. One child
      presented as acute febrile encephalopathy which has not been described as a
      presenting feature. 

PMID- 24037496
TI  - Dapsone-induced isolated acute pancreatitis in a child with linear IgA
      dermatitis.

PMID- 24037497
TI  - Successful treatment of atrial flutter with propafenone and synchronized
      cardioversion in a newborn.

PMID- 24037498
TI  - Prognostic value of neutrophil-to-lymphocyte ratio in patients with glioblastoma.

PMID- 24037500
TI  - Biotechnological production of colorants.
AB  - The color of food and drinks is important, as it is associated with freshness and
      taste. Despite that natural colorants are more expensive to produce, less stable
      to heat and light, and less consistent in color range, natural colorants have
      been gaining market share in recent years. The background is that artificial
      colorants are often associated with negative health aspects. Considerable
      progress has been made towards the fermentative production of some colorants.
      Because colorant biosynthesis is under close metabolic control, extensive strain
      and process development are needed in order to establish an economical production
      process. Another approach is the synthesis of colors by means of
      biotransformation of adequate precursors. Algae represent a promising group of
      microorganisms that have shown a high potential for the production of different
      colorants, and dedicated fermentation and downstream technologies have been
      developed. This chapter reviews the available information with respect to these
      approaches.

PMID- 24037499
TI  - Neurological and cytological response as potential early predictors of time-to
      progression and overall survival in patients with leptomeningeal carcinomatosis
      treated with intrathecal liposomal cytarabine: a retrospective cohort study.
AB  - Interesting neurological and cytological response rates after intrathecal (i.t)
      liposomal cytarabine have been observed in patients with leptomeningeal
      carcinomatosis (LMC) from solid tumors. However, the potential use of those
      responses as early predictors of time-to-progression (TTP) and overall survival
      (OS) is unexplored. 27 consecutive patients with LMC treated with 50 mg i.t
      liposomal cytarabine under compassionate drug use were retrospectively studied.
      All patients received i.t treatment every 2 weeks during induction and every 4
      weeks during maintenance periods. Neurological and cytological responses were
      assessed before every liposomal cytarabine cycle. Most of the patients were
      female (17/27) diagnosed with breast cancer (15/27). A complete neurological
      response was seen among 11 % of the patients; partial response in 22 % of the
      patients; stable disease in 30 % of the patients and progressive disease in 37 %
      of them. Cytological assessment was available in 11/27 patients showing a 26 %
      complete response rate. The median time to neurological and cytological response
      was 15 days and 14 days, respectively. Patients showing a combined neurological
      and cytological response showed a significantly longer median TTP (122 vs. 3
      days; p = 0.001) and OS (141 vs. 3 days; p = 0.002) compared to those showing
      both neurological and cytological progression. No grade 4 toxicities were
      recorded. According to these preliminary results, early neurological and
      cytological responses may be further studied as early predictors of TTP and OS in
      patients receiving i.t liposomal cytarabine for LMC.

PMID- 24037501
TI  - [The Mini-Audio-Test (MAT). Screening inventory for hearing loss starting at the
      age of 50].
AB  - BACKGROUND: Progredient hearing loss is a common symptom, which is hard to detect
      early. This study presents an assessment to face this problem. METHODS: 1,159
      subjects between the age of 50 and 75 have been investigated by a 12 question
      profile about their hearing in different situations. The answers have been rated
      by weighted points and compared with the pure-tone audiogram of the subjects.
      RESULTS: 6 of the 12 questions were suitable to detect a hearing loss of 25 dB in
      one of the 4 frequencies 0,5-1-2-4 kHz. For subjects under age of 60 a cutoff
      value of 3, for subjects aged 60 years or older a cutoff value of 2 points could
      be set for the 6 questions including "Mini-Audio-Test" (MAT). DISCUSSION: The
      "Mini-Audio-Test" is able to detect a hearing loss of 25 dB at least in one of
      the 4 frequencies by a sensitivity of 78%, 95% confidence interval (71,8%,
      83,2%), for the younger group of subjects and by 69%, 95% confidence interval
      (66,0%, 72,6%), for the older one. Subjects with a pathological score should be
      examined by an ENT-physician.

PMID- 24037502
TI  - Night shift work characteristics and occupational co-exposures in industrial
      plants in Lodz, Poland.
AB  - OBJECTIVES: Night shift work involving circadian rhythm disruption has been
      classified by IARC as a probably carcinogenic to humans (Group 2A). Little is
      known about co-exposures of the night shift work in occupational settings. The
      aim of our study was to characterize night shift work systems and industrial
      exposures occurring in the manufacturing plants in Lodz, Poland, where night
      shift work system operates, with particular focus on potential carcinogens.
      MATERIAL AND METHODS: Data on the night shift work systems and hazardous agents
      were collected through survey performed in 44 enterprises. The identified
      hazardous agents were checked using the IARC carcinogen list, and the harmonized
      EU classification of chemical substances. We also examined databases of the
      Central Register of Data on exposure to substances, preparations, agents and
      technological processes showing carcinogenic or mutagenic properties in Poland.
      RESULTS: The most common system of work among studied enterprises employed 3 (8
      hour) shifts within a 5-day cycle. We identified as many as 153 hazards occurring
      in the environment of the plants, with noise, carbon monoxide and formaldehyde
      recorded as the most common ones. Out of these hazards, 11 agents have been
      classified by IARC to group 1 - carcinogenic to humans, whereas 10 agents have
      been classified as carcinogens by the regulation of European Classification of
      carcinogens. Analysis of the data from the Central Register revealed that 6
      plants reported presence of carcinogens in the environment of work. CONCLUSIONS:
      In our study we observed that in none of the workplaces the night shift work was
      a single exposure. Further epidemiological studies focusing on investigation of
      health effects of the night shift work should identify occupational co-exposures
      and examine them as potential confounders.

PMID- 24037503
TI  - Quantitative SPECT/CT: SPECT joins PET as a quantitative imaging modality.
AB  - The introduction of combined modality single photon emission computed tomography
      (SPECT)/CT cameras has revived interest in quantitative SPECT. Schemes to
      mitigate the deleterious effects of photon attenuation and scattering in SPECT
      imaging have been developed over the last 30 years but have been held back by
      lack of ready access to data concerning the density of the body and photon
      transport, which we see as key to producing quantitative data. With X-ray CT data
      now routinely available, validations of techniques to produce quantitative SPECT
      reconstructions have been undertaken. While still suffering from inferior spatial
      resolution and sensitivity compared to positron emission tomography (PET)
      imaging, SPECT scans nevertheless can be produced that are as quantitative as PET
      scans. Routine corrections are applied for photon attenuation and scattering,
      resolution recovery, instrumental dead time, radioactive decay and cross
      calibration to produce SPECT images in units of kBq.ml(-1). Though clinical
      applications of quantitative SPECT imaging are lacking due to the previous non
      availability of accurately calibrated SPECT reconstructions, these are beginning
      to emerge as the community and industry focus on producing SPECT/CT systems that
      are intrinsically quantitative. 

PMID- 24037504
TI  - Toward embedded detection of polyps in WCE images for early diagnosis of
      colorectal cancer.
AB  - PURPOSE: Wireless capsule endoscopy (WCE) is commonly used for noninvasive
      gastrointestinal tract evaluation, including the detection of mucosal polyps. A
      new embeddable method for polyp detection in wireless capsule endoscopic images
      was developed and tested. METHODS: First, possible polyps within the image were
      extracted using geometric shape features. Next, the candidate regions of interest
      were evaluated with a boosting based method using textural features. Each step
      was carefully chosen to accommodate hardware implementation constraints. The
      method's performance was evaluated on WCE datasets including 300 images with
      polyps and 1,200 images without polyps. Hardware implementation of the proposed
      approach was evaluated to quantitatively demonstrate the feasibility of such
      integration into the WCE itself. RESULTS: The boosting based polyp classification
      demonstrated a sensitivity of 91.0 %, a specificity of 95.2 % and a false
      detection rate of 4.8 %. This performance is close to that reported recently in
      systems developed for an online analysis of video colonoscopy images. CONCLUSION:
      A new method for polyp detection in videoendoscopic WCE examinations was
      developed using boosting based approach. This method achieved good classification
      performance and can be implemented in situ with embedded hardware.

PMID- 24037505
TI  - Host plant effects on the behaviour and performance of Amblyseius swirskii
      (Acari: Phytoseiidae).
AB  - Biological control in ornamental crops is challenging due to the wide diversity
      of crops and cultivars. In this study, we tested the hypothesis that trichome
      density on different host plants influences the behavior and performance of the
      predatory mite Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae).
      Behavioural observations of this predator in the presence or absence of prey
      (western flower thrips, Frankliniella occidentalis Pergande) (Thysanoptera:
      Thripidae) were done on leaf squares of ornamental plant species differing in
      trichome density (rose, chrysanthemum and gerbera) and compared to a smooth
      surface (plastic). Tomato leaves were used to observe the influence of glandular
      trichomes. The performance of A. swirskii was assessed by measuring predation and
      oviposition rate. Behaviour of A. swirskii was influenced by plant species. Up to
      a certain density of trichomes, trichome number had a negative effect on walking
      speed. It was highest on plastic, followed by rose. No differences were found
      among chrysanthemum, gerbera and tomato. Walking speed was slightly higher on
      disks without prey. Proportion of time spent walking was the same on leaf disks
      of all plant species, with and without prey. No effect of glandular trichomes on
      tomato leaves was seen. Most thrips were killed and consumed on gerbera, and
      least on rose. Predation rates on chrysanthemum and plastic were intermediate. In
      contrast, no differences in oviposition rate were found among plant species. The
      results of this study indicate that trichome density can explain some of the
      variability in efficacy of A. swirskii on different crops. Release rates of A.
      swirskii may need to be adjusted depending on the crop in which it is used. 

PMID- 24037506
TI  - Childhood interparental conflict and HPA axis activity in young adulthood:
      examining nonlinear relations.
AB  - Relations between early adversity and the neuroendocrine stress response are most
      often tested in a linear framework. Findings from studies of nonlinear relations
      between early stress and reactivity in childhood are suggestive, but curvilinear
      associations between childhood family stress and stress reactivity at later
      developmental stages remain unexplored. The current study examined curvilinear
      relations between childhood interparental conflict (IPC) and cortisol reactivity
      in young adulthood. Participants (n = 91; Mean age = 18.7, SD = .97; 59% White,
      25% Hispanic) reported on the frequency and intensity of childhood exposure to
      IPC and salivary cortisol was sampled before and after a challenging
      interpersonal role-play task. Significant curvilinear relations were found such
      that higher total cortisol and cortisol reactivity during the task was observed
      among youth reporting lower and higher frequency of IPC, suggesting that moderate
      IPC exposure may be associated with lower cortisol activity at a later
      developmental stage.

PMID- 24037507
TI  - Mechanism and consequence of the autoactivation of p38alpha mitogen-activated
      protein kinase promoted by TAB1.
AB  - p38alpha mitogen-activated protein kinase (p38alpha) is activated by a variety of
      mechanisms, including autophosphorylation initiated by TGFbeta-activated kinase 1
      binding protein 1 (TAB1) during myocardial ischemia and other stresses. Chemical
      genetic approaches and coexpression in mammalian, bacterial and cell-free systems
      revealed that mouse p38alpha autophosphorylation occurs in cis by direct
      interaction with TAB1(371-416). In isolated rat cardiac myocytes and perfused
      mouse hearts, TAT-TAB1(371-416) rapidly activates p38 and profoundly perturbs
      function. Crystal structures and characterization in solution revealed a
      bipartite docking site for TAB1 in the p38alpha C-terminal kinase lobe. TAB1
      binding stabilizes active p38alpha and induces rearrangements within the
      activation segment by helical extension of the Thr-Gly-Tyr motif, allowing
      autophosphorylation in cis. Interference with p38alpha recognition by TAB1
      abolishes its cardiac toxicity. Such intervention could potentially circumvent
      the drawbacks of clinical pharmacological inhibitors of p38 catalytic activity. 

PMID- 24037508
TI  - MicroRNA-based discovery of barriers to dedifferentiation of fibroblasts to
      pluripotent stem cells.
AB  - Individual microRNAs (miRNAs) can target hundreds of mRNAs forming networks of
      presumably cooperating genes. To test this presumption, we functionally screened
      miRNAs and their targets in the context of dedifferentiation of mouse fibroblasts
      to induced pluripotent stem cells (iPSCs). Along with the miR-302-miR-294 family,
      the miR-181 family arose as a previously unidentified enhancer of the initiation
      phase of reprogramming. Endogenous miR-181 miRNAs were transiently elevated with
      the introduction of Pou5f1 (also known as Oct4), Sox2 and Klf4 (referred to as
      OSK), and miR-181 inhibition diminished iPSC colony formation. We tested the
      functional contribution of 114 individual targets of the two families, revealing
      25 genes that normally suppress initiation. Coinhibition of targets cooperatively
      promoted both the frequency and kinetics of OSK-induced reprogramming. These data
      establish two of the largest functionally defined networks of miRNA-mRNA
      interactions and reveal previously unidentified relationships among genes that
      act together to suppress early stages of reprogramming. 

PMID- 24037509
TI  - The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward,
      cocaine seeking and cocaine-induced locomotor activity in rats.
AB  - RATIONALE: There is a focus on developing D3 receptor antagonists as cocaine
      addiction treatments. OBJECTIVE: We investigated the effects of a novel selective
      D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food
      reward, spontaneous locomotor activity and cocaine-induced locomotor activity in
      rats. METHODS: In Experiment 1, rats were trained to self-administer cocaine
      under a progressive ratio (PR) schedule of reinforcement and tested with vehicle
      or one of three doses of SR 21502. In Experiment 2, animals were trained to self
      administer cocaine under a fixed ratio schedule of reinforcement followed by
      extinction of the response. Then, animals were tested with vehicle or one of the
      SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3,
      animals were trained to lever press for food under a PR schedule and tested with
      vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups
      of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or
      cocaine (10 mg/kg, IP)-induced locomotor activity, respectively. RESULTS: SR
      21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in
      breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5
      and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but
      failed to reduce food self-administration and spontaneous locomotor activity.
      CONCLUSIONS: SR 21502 decreases cocaine reward, cocaine-seeking and locomotor
      activity at doses that have no effect on food reward or spontaneous locomotor
      activity. These data suggest SR 21502 may selectively inhibit cocaine's
      rewarding, incentive motivational and stimulant effects.

PMID- 24037510
TI  - Trait differences in response to chronic nicotine and nicotine withdrawal in
      rats.
AB  - INTRODUCTION: Understanding an individual's vulnerability to drug addiction has
      important implications for the development of effective personal treatment plans.
      Although theories acknowledge impulsive behaviour as a key component of drug
      addiction, little is known about the influence of trait impulsivity on an
      individual's susceptibility to the effects of psychostimulants on impulsivity at
      critical phases of the addiction cycle. METHODS: This study investigated the
      short and longer-term effects of chronic nicotine administration on impulsive
      choice in rats selected for high (HI) and low impulsivity (LI) on a delay
      discounting task. Rats prepared with subcutaneously osmotic mini-pumps received
      either nicotine (3.16 mg/kg/day [freebase]) or saline for 7 days. Performance was
      assessed during chronic treatment, early and late withdrawal, and in response to
      acute nicotine challenges following prolonged abstinence. RESULTS: Chronic
      nicotine increased impulsive choice in LI but not HI animals. Spontaneous
      withdrawal was associated with a nicotine abstinence syndrome, the early stages
      of which were characterised by opposing effects on impulsive choice in HI and LI
      animals. A transient decrease in impulsivity was observed in HI animals whilst
      the LI group remained more impulsive for up to 1 week following drug termination.
      Following normalisation of behaviour, acute nicotine challenges (0.125, 0.25, 0.5
      mg/kg, SC) markedly increased impulsive choice regardless of trait impulsivity
      and drug history. CONCLUSION: The results indicate that only LI individuals are
      vulnerable to chronic drug- and withdrawal-induced impairments in self-control
      which may increase the likelihood of the transition to, and maintenance of,
      nicotine dependence.

PMID- 24037511
TI  - Bisphosphonate-related osteonecrosis of the jaw in patients with breast cancer.
AB  - Bisphosphonate represents a well-established treatment option in the management
      of metastatic bone disease and bone loss/osteoporosis in women with breast
      cancer. These drugs reduce osteoclast. Some bisphosphonate also have osteoblastic
      function leading to a reducted bone turnover and thereby skeletal-related events.
      The aim of this review is to evaluate the bisphosphonate-related osteonecrosis of
      the jaw in patients with breast cancer. Based on the proven effect of bone
      protection during adjuvant endocrine therapy, new treatment guidelines recommend
      the routine use of bisphosphonates to prevent bone loss during adjuvant therapy,
      which may likely become the standard practice. 

PMID- 24037512
TI  - Influence of transition metals on Streptomyces coelicolor and S. sioyaensis and
      generation of chromate-reducing mutants.
AB  - Bacteria-assisted bioremediation is widely recognized as a low-cost method to
      minimize the consequences of soil pollution with toxic metals originating from
      industrial sites. Strains used in bioremediation have to deal with high metal
      load via biosorption, reduction, bioprecipitation, metal sequestration, and/or
      chelation. Actinobacteria, and streptomycetes in particular, are considered a
      perspective group for bioremediation as natural soil inhabitants with extensive
      secondary metabolism. Nevertheless, there is no reference information on survival
      of the model streptomycetes in the presence of the most abundant metal
      pollutants. Also, there are no reports describing the selection approaches
      towards improvement of bioremediation properties. In this work, the resistance of
      Streptomyces coelicolor M145 and Streptomyces sioyaensis Lv81 to certain
      transition metals and their growth under different pH values are described for
      the first time. Spontaneous chromate-resistant S. sioyaensis Lv81-138 strain was
      selected in the course of this work. Strain Lv81-138 is the most efficient
      actinobacterial Cr(VI) reducer reported so far, capable of converting 12 mmol/L
      of Cr(VI) into Cr(III) in a medium supplemented with 50 mmol/L K2CrO4.

PMID- 24037513
TI  - Identification and structure elucidation of a novel antifungal compound produced
      by Pseudomonas aeruginosa PGPR2 against Macrophomina phaseolina.
AB  - Pseudomonas aeruginosa PGPR2 was found to protect mungbean plants from charcoal
      rot disease caused by Macrophomina phaseolina. Secondary metabolites from the
      culture supernatant of P. aeruginosa PGPR2 were extracted with ethyl acetate and
      the antifungal compound was purified by preparative HPLC using reverse phase
      chromatography. The purified compound showed antifungal activity against M.
      phaseolina and other phytopathogenic fungi (Fusarium sp., Rhizoctonia sp.
      Alternaria sp., and Aspergillus sp.). The structure of the purified compound was
      determined using (1)H, (13)C, 2D NMR spectra and liquid chromatography-mass
      spectrometry (LC-MS). Spectral data suggest that the antifungal compound is 3,4
      dihydroxy-N-methyl-4-(4-oxochroman-2-yl)butanamide, with the chemical formula
      C14H17NO5 and a molecular mass of 279. Though chemically synthesized chromanone
      derivatives have been shown to have antifungal activity, we report for the first
      time, the microbial production of a chromanone derivative with antifungal
      activity. This ability of P. aeruginosa PGPR2 makes it a suitable strain for
      biocontrol. 

PMID- 24037514
TI  - Fuzzy control with genetic algorithm in a batch bioreactor.
AB  - In this study, the growth medium temperature in a batch bioreactor was controlled
      at the set point by using fuzzy model-based control method. Fuzzy control
      parameters which are membership functions and relation matrix were found using
      genetic algorithm. Heat input given from the immersed heater and the cooling
      water flow rate were selected as the manipulated variables in order to control
      the growth medium temperature in the bioreactor. Controller performance was
      tested in the face of different types of input variables. To eliminate the noise
      on the temperature measurements, first-order filter was used in the control
      algorithm. The achievement of the temperature control was analyzed in terms of
      both microorganism concentration which was reached at the end of the stationary
      phase and the performance criteria of Integral of the Absolute Error. It was
      concluded that the cooling flow rate was suitable as manipulated variable with
      regard to microorganism concentration. On the other hand, performance of the
      controller was satisfactory when the heat input given from the immersed heater
      was manipulated variable. 

PMID- 24037515
TI  - New bacteriocin from Bacillus clausii strainGM17: purification, characterization,
      and biological activity.
AB  - A bacteriocin-producing strain (9,000 AU/ml) was isolated from the rhizosphere of
      Algerian healthy plants Ononis angustissima Lam. and identified as Bacillus
      clausii strain GM17. The bacteriocin, called Bac-GM17, was purified from the
      culture supernatant after heat treatment, ammonium sulfate precipitation,
      Sephadex G-50 chromatography and Mono Q fast-performance liquid chromatography
      (FPLC). Based on matrix-assisted laser desorption ionization-time of flight mass
      spectrometry analysis, the purified Bac-GM17 is a monomer protein with a
      molecular mass of 5,158.11 Da. The N-terminal sequencing allowed for the
      straightforward identification of its first 20 residues, which were of pure
      bacteriocin. It also revealed that this bacteriocin contained a unique sequence,
      namely DWTCSKWSCLVCDDCSVELT, which suggests the identification of a novel
      compound. Bac-GM17 was extremely heat stable (20 min at 120  degrees C) and was
      stable within the pH range (3-9). It was found to be resistant to the proteolytic
      action of trypsin, pepsin, papain, pronase E, and proteinase K. It was also noted
      to display a bactericidal mode of action against Agrobacterium tumefaciens C58
      and a fungistatic mode of action against Candida tropicalis R2 CIP203.

PMID- 24037516
TI  - Immobilized Rhodotorula mucilaginosa: a novel urethanase-producing strain for
      degrading ethyl carbamate.
AB  - Rhodotorula mucilaginosa, producing the ethyl carbamate (EC)-degrading enzyme,
      urethanase, was newly isolated from the Chinese rice wine making process. It
      removed 80 % of EC when it was incubated with 5.0 g/L EC. It grew and stably
      produced urethanase, with pH ranging from 7.0 to 3.0. In addition, urethanase
      production by R. mucilaginosa was systematically optimized. Glucose, yeast
      extract, peptone, and inoculum size were selected with the Plackett-Burman
      design. They were further optimized via uniform design and determined to be 24.6
      g/L, 2.5 g/L, 23.1 g/L, and 65.8 mL/500 mL, respectively. Urethanase activity
      reached 4,340.0 U/L in the optimal fermentation condition. Furthermore, cell
      immobilization of R. mucilaginosa in calcium alginate/chitosan was applied to
      improve cell resistance to environmental stresses. The immobilized cells removed
      51.6 % of EC in commercial rice wine, which was 10 times more than that of the
      free cells. It indicated that the immobilized R. mucilaginosa was effective for
      degrading EC.

PMID- 24037517
TI  - Functional magnetic mesoporous nanoparticles for efficient purification of
      laccase from fermentation broth in magnetically stabilized fluidized bed.
AB  - A magnetically stabilized fluidized bed (MSFB) with the Cu(2+)-chelated magnetic
      mesoporous silica nanoparticles (MMSNPs-Cu(2+)) was established to purify laccase
      directly from the fermentation broth of Trametes versicolor. The MMSNPs-Cu(2+)
      particles in the MSFB maintained a stable bed expansion of two to threefold at a
      flow rate of 120-180 cm/h. At the optimal magnetic field intensity of 120 Gs,
      both the maximal Bodenstein number and the smallest axial dispersion coefficient
      were achieved, which resulted in a stable fluidization stage. The dynamic binding
      capacity of laccase in the MSFB decreased from 192.5 to144.3 mg/g when the flow
      velocity through the bed increased from 44.2 to 69.8 cm/h. The MSFB with MMSNPs
      Cu(2+) achieved efficient laccase purification from the fermentation broth with
      62.4-fold purification of laccase and 108.9 % activity yield. These results
      provided an excellent platform for the application of these magnetic mesoporous
      nanoparticles integrated with the MSFB in developing novel protein purification
      process.

PMID- 24037518
TI  - Genotypic diversity of mosquitocidal bacteria (Bacillus sphaericus, B.
      thuringiensis, and B. cereus) newly isolated from natural sources.
AB  - In the present study, to comprehend the genetic diversity of mosquitocidal
      bacteria, the genotypic analysis of 30 strains of Bacillus species isolated newly
      from diverse environmental sources has been conducted. Randomly amplified
      polymorphic DNA polymerase chain reaction was conducted to characterize the
      genotype diversity between the bacterial strains. The matrix of scores from each
      bacterial DNA was analyzed, and the correlation between the co-efficients and the
      similarity matrix data was computed. Clusters from dendrogram showing diversity
      among isolates could be distinguished genetically based on their origin of
      isolates. The first major cluster consists of 43 strains grouped under various
      subclusters (91.489 %). A second cluster contains only four strains (8.511 %). An
      average similarity value of 0.36 revealed the dendrogram split into 28 distinct
      "groups" or "clusters," allowing almost a complete separation of strains within
      the Bacillus group isolated from various sources and thus facilitating assessment
      of genetic diversity of species and subspecies level. The conclusion from the
      result was that there was broad diversity among the mosquitocidal strains, and
      cluster analysis revealed the associations among the isolates based on their
      origin. A high level of polymorphism with distinct genetic lineages consequent to
      the source of origin of bacterial strains is the significant impact of this
      study.

PMID- 24037519
TI  - 1H, 13C and 15N resonance assignments of the VWA domain of Saccharomyces
      cerevisiae Rpn10, a regulatory subunit of 26S proteasome.
AB  - Rpn10 is a ubiquitin receptor of the 26S proteasome, and plays an important role
      in poly-ubiquitinated proteins recognition in the ubiquitin-proteasome protein
      degradation pathway. It is located in the 19S regulatory particle and interacts
      with several subunits of both lid and base complexes. Bioinformatics analysis of
      yeast Rpn10 suggests that it contains a von Willebrand (VWA domain) and a C
      terminal tail containing a Ub-interacting motif. Studies of Saccharomyces
      cerevisiae Rpn10 suggested that its VWA domain might participate in interactions
      with subunit from both lid and base subcomplexes of the 19S regulatory particle.
      Herein, we report the chemical shift assignments of (1)H, (13)C and (15)N atoms
      of the VWA domain of S. cerevisiae Rpn10, which provide the basis for further
      structural and functional studies of Rpn10 by solution NMR technique. 

PMID- 24037520
TI  - Comparison between drug-induced and K+-induced changes in molar acid extrusion
      fluxes (JH+) and in energy consumption rates in astrocytes.
AB  - Neuronal excitation leads to an increase of the extracellular K(+) concentration
      ([K(+)]o) in brain. This increase has at least two energy-consuming consequences:
      (1) a depolarization-mediated change in intracellular pH (pHi) in astrocytes due
      to depolarization-mediated increased activity of the acid-extruding
      Na(+)/bicarbonate transporter NBCe1 (driven by secondary active transport,
      supported by ion gradients established by the Na(+), K(+)-ATPase); and (2)
      activation of cellular reuptake of K(+) mediated by the Na(+), K(+)-ATPase in
      both neurons and astrocytes. Astrocytic, but not neuronal increase in NBCe1
      activity and pHi is also seen after chronic treatment with either of the two anti
      bipolar drugs carbamazepine or valproic acid. The third 'classical' anti-bipolar
      drug, 'lithium' increases astrocytic pHi by a different mechanism (stimulation of
      the acid extruding Na(+)/H(+) exchanger NHE1). The acid extruder fluxes, which
      depend upon the change in pHi per time unit (DeltapHi/Deltat) and intracellular
      buffering power, have not been established in most of these situations. Therefore
      their stimulatory effects on energy metabolism has not been quantitated. This has
      been done in the present study in cultured mouse astrocytes. pHi was determined
      using the fluorescent pH-sensitive indicator BCECF-AM and an Olympus IX71 live
      cell imaging fluorescence microscope. Molar acid extrusion fluxes (indicating
      transporter activity) were determined as pHi changes/min during recovery after
      acid-loading with NH3/NH4 (+), NBCe1 mRNA and protein expression in the cultured
      cells by, respectively RT-PCR and Western blotting. Drug-induced up-regulation of
      acid extrusion flux was slow and less than physiologically seen after increase in
      K(+) concentration. Energetically, K(+) uptake is much costlier than NBCe1
      activity.

PMID- 24037521
TI  - Automated method for the rapid and precise estimation of adherent cell culture
      characteristics from phase contrast microscopy images.
AB  - The quantitative determination of key adherent cell culture characteristics such
      as confluency, morphology, and cell density is necessary for the evaluation of
      experimental outcomes and to provide a suitable basis for the establishment of
      robust cell culture protocols. Automated processing of images acquired using
      phase contrast microscopy (PCM), an imaging modality widely used for the visual
      inspection of adherent cell cultures, could enable the non-invasive determination
      of these characteristics. We present an image-processing approach that accurately
      detects cellular objects in PCM images through a combination of local contrast
      thresholding and post hoc correction of halo artifacts. The method was thoroughly
      validated using a variety of cell lines, microscope models and imaging
      conditions, demonstrating consistently high segmentation performance in all cases
      and very short processing times (<1 s per 1,208 * 960 pixels image). Based on the
      high segmentation performance, it was possible to precisely determine culture
      confluency, cell density, and the morphology of cellular objects, demonstrating
      the wide applicability of our algorithm for typical microscopy image processing
      pipelines. Furthermore, PCM image segmentation was used to facilitate the
      interpretation and analysis of fluorescence microscopy data, enabling the
      determination of temporal and spatial expression patterns of a fluorescent
      reporter. We created a software toolbox (PHANTAST) that bundles all the
      algorithms and provides an easy to use graphical user interface. Source-code for
      MATLAB and ImageJ is freely available under a permissive open-source license.

PMID- 24037522
TI  - Characteristics and outcomes of anterior hyaloidal fibrovascular proliferation in
      lasered retinopathy of prematurity. The Indian Twin Cities Retinopathy of
      Prematurity Study (ITCROPS) report number 4.
AB  - To describe the characteristics and treatment outcomes of an unreported, late
      vitreous hemorrhage due to anterior hyaloidal fibrovascular proliferation in
      laser-regressed retinopathy of prematurity (ROP). Interventional case series. In
      the ongoing Indian Twin Cities ROP study database, consecutive cases with
      isolated late vitreous hemorrhage at least one year after laser-regressed disease
      were analyzed retrospectively. Anterior hyaloidal fibrovascular proliferation was
      diagnosed primarily using scleral depression. Anterior retinal cryopexy with
      adjunctive treatments was performed. The main outcome measure was clinical
      resolution of new vessels with no recurrent hemorrhage over a 1-year period.
      Vitreous hemorrhage, at two to eight years of age, developed in three eyes of
      three children out of 1,168 ROP lasered eyes. All had received laser for zone I
      disease as neonates, with no subsequent sequelae. Evaluation revealed filiform
      new vessels at the posterior vitreous base involving inferior 180 degrees  with
      absence of any other source of hemorrhage. All underwent anterior retinal
      cryopexy to the affected area. Simultaneous additional treatment, based on
      intraoperative findings, included one case each of peripheral laser
      photocoagulation, lens-sparing vitrectomy and intravitreal bevacizumab. All three
      showed successful regression and non-recurrence of vitreous hemorrhage with
      improvement of vision >20/40 at an intermediate follow-up of two years. Anterior
      hyaloidal fibrovascular proliferation is an unreported and rare cause of vitreous
      hemorrhage, appearing years after laser-regressed ROP. It has a good response to
      interventional treatment. Meticulous scleral depression of the vitreous base
      under anesthesia is useful to detect this rare source of vitreous hemorrhage. 

PMID- 24037523
TI  - Genetic inactivation or pharmacological inhibition of Pdk1 delays development and
      inhibits metastasis of Braf(V600E)::Pten(-/-) melanoma.
AB  - Phosphoinositide-dependent kinase-1 (PDK1) is a serine/threonine protein kinase
      that phosphorylates members of the conserved AGC kinase superfamily, including
      AKT and protein kinase C (PKC), and is implicated in important cellular processes
      including survival, metabolism and tumorigenesis. In large cohorts of nevi and
      melanoma samples, PDK1 expression was significantly higher in primary melanoma,
      compared with nevi, and was further increased in metastatic melanoma. PDK1
      expression suffices for its activity, owing to auto-activation, or elevated
      phosphorylation by phosphoinositide 3'-OH-kinase (PI3K). Selective inactivation
      of Pdk1 in the melanocytes of Braf(V600E)::Pten(-/-) or Braf(V600E)::Cdkn2a(-/
      )::Pten(-/-) mice delayed the development of pigmented lesions and melanoma
      induced by systemic or local administration of 4-hydroxytamoxifen. Melanoma
      invasion and metastasis were significantly reduced or completely prevented by
      Pdk1 deletion. Administration of the PDK1 inhibitor GSK2334470 (PDKi) effectively
      delayed melanomagenesis and metastasis in Braf(V600E)::Pten(-/-) mice. Pdk1(-/-)
      melanomas exhibit a marked decrease in the activity of AKT, P70S6K and PKC.
      Notably, PDKi was as effective in inhibiting AGC kinases and colony forming
      efficiency of melanoma with Pten wild-type (WT) genotypes. Gene expression
      analyses identified Pdk1-dependent changes in FOXO3a-regulated genes, and
      inhibition of FOXO3a restored proliferation and colony formation of Pdk1(-/-)
      melanoma cells. Our studies provide direct genetic evidence for the importance of
      PDK1, in part through FOXO3a-dependent pathway, in melanoma development and
      progression. 

PMID- 24037525
TI  - Wnt-driven intestinal tumourigenesis is suppressed by Chk1 deficiency but
      enhanced by conditional haploinsufficiency.
AB  - Chk1 is essential in maintaining genomic stability due to its role in cell cycle
      regulation. Several recent studies have indicated that the abrogation of
      checkpoints in tumourigenesis through the inhibition of Chk1 may be of
      therapeutic value. To further investigate the role of Chk1 in the mouse small
      intestine and its potential role as a therapy for colorectal cancer, we
      simultaneously deleted Chk1 and Apc in the mouse small intestine. We found that
      homozygous loss of Chk1 is not compatible with Wnt-driven proliferation and
      resulted in the suppression of Wnt-driven tumourigenesis in the mouse small
      intestine. In contrast, heterozygous loss of Chk1 in a Wnt-driven background
      resulted in an increase in DNA damage and apoptosis and accelerated both tumour
      development and progression. 

PMID- 24037524
TI  - ASCL1 and RET expression defines a clinically relevant subgroup of lung
      adenocarcinoma characterized by neuroendocrine differentiation.
AB  - ASCL1 is an important regulatory transcription factor in pulmonary neuroendocrine
      (NE) cell development, but its value as a biomarker of NE differentiation in lung
      adenocarcinoma (AD) and as a potential prognostic biomarker remains unclear. We
      examined ASCL1 expression in lung cancer samples of varied histologic subtype,
      clinical outcome and smoking status and compared with expression of traditional
      NE markers. ASCL1 mRNA expression was found almost exclusively in smokers with
      AD, in contrast to non-smokers and other lung cancer subtypes. ASCL1 protein
      expression by immunohistochemical (IHC) analysis correlated best with
      synaptophysin compared with chromogranin and CD56/NCAM. Analysis of a compendium
      of 367 microarray-based gene expression profiles in stage I lung adenocarcinomas
      identified significantly higher expression levels of the RET oncogene in ASCL1
      positive tumors (ASCL1(+)) compared with ASCL1(-) tumors (q-value <10(-9)). High
      levels of RET expression in ASCL1(+) but not in ASCL1(-) tumors was associated
      with significantly shorter overall survival (OS) in stage 1 (P=0.007) and in all
      AD (P=0.037). RET protein expression by IHC had an association with OS in the
      context of ASCL1 expression. In silico gene set analysis and in vitro experiments
      by ASCL1 shRNA in AD cells with high endogenous expression of ASCL1 and RET
      implicated ASCL1 as a potential upstream regulator of the RET oncogene. Also,
      silencing ASCL1 in AD cells markedly reduced cell growth and motility. These
      results suggest that ASCL1 and RET expression defines a clinically relevant
      subgroup of ~10% of AD characterized by NE differentiation.

PMID- 24037526
TI  - Repression of miR-126 and upregulation of adrenomedullin in the stromal
      endothelium by cancer-stromal cross talks confers angiogenesis of cervical
      cancer.
AB  - miR-126 is an endothelial-specific microRNA essential for maintaining vessel
      integrity during development. Its role of tumor angiogenesis in cancer stroma is
      unclear. This study investigated the temporal and spatial expression and the role
      of miR-126 in the course of cervical carcinogenesis. miR-126 was found to be
      mainly expressed in the stromal endothelium of the uterine cervix. This
      downregulation was recapitulated in a cell coculture model, wherein cross talk of
      cervical cancer cells and fibroblasts induced a downregulation of miR-126 in
      human umbilical vein endothelial cells, with consequent increase of tube
      formation. Coinjection of cancer-associated fibroblasts of human cervix enhanced
      tumorigenesis of cervical cancer cells, with an increase of microvessel density
      and dye retention in the tumor vasculature. In association with angiogenesis,
      host-originated miR-126 in these xenograft tumors was progressively
      downregulated, whereas supplement of the miR-126 precursor in the coinjection
      suppressed angiogenesis and tumor growth. A proangiogenic gene adrenomedullin
      (ADM), which was found to be upregulated in the stroma of cervical cancer and
      which localized mainly in the blood and lymphatic vessels, was identified as a
      target of inhibition by miR-126 at the carcinoma in situ-to-invasion stage. The
      study suggests a cancer stroma cross talk induced repression of miR-126 and
      upregulation of ADM, and probably other proangiogenic factors, to facilitate
      angiogenesis and invasion growth of cervical cancer. 

PMID- 24037528
TI  - MiR-200 can repress breast cancer metastasis through ZEB1-independent but moesin
      dependent pathways.
AB  - The microRNA-200 (miR-200) family has a critical role in regulating epithelial
      mesenchymal transition and cancer cell invasion through inhibition of the E
      cadherin transcriptional repressors ZEB1 and ZEB2. Recent studies have indicated
      that the miR-200 family may exert their effects at distinct stages in the
      metastatic process, with an overall effect of enhancing metastasis in a syngeneic
      mouse breast cancer model. We find in a xenograft orthotopic model of breast
      cancer metastasis that ectopic expression of members of the miR-200b/200c/429,
      but not the miR-141/200a, functional groups limits tumour cell invasion and
      metastasis. Despite modulation of the ZEB1-E-cadherin axis, restoration of ZEB1
      in miR-200b-expressing cells was not able to alter metastatic potential
      suggesting that other targets contribute to this process. Instead, we found that
      miR-200b repressed several actin-associated genes, with the knockdown of the
      ezrin-radixin-moesin family member moesin alone phenocopying the repression of
      cell invasion by miR-200b. Moesin was verified to be directly targeted by miR
      200b, and restoration of moesin in miR-200b-expressing cells was sufficient to
      alleviate metastatic repression. In breast cancer cell lines and patient samples,
      the expression of moesin significantly inversely correlated with miR-200
      expression, and high levels of moesin were associated with poor relapse-free
      survival. These findings highlight the context-dependent effects of miR-200 in
      breast cancer metastasis and demonstrate the existence of a moesin-dependent
      pathway, distinct from the ZEB1-E-cadherin axis, through which miR-200 can
      regulate tumour cell plasticity and metastasis. 

PMID- 24037527
TI  - The B-cell receptor orchestrates environment-mediated lymphoma survival and drug
      resistance in B-cell malignancies.
AB  - Specific niches within the lymphoma tumor microenvironment (TME) provide
      sanctuary for subpopulations of tumor cells through stromal cell-tumor cell
      interactions. These interactions notably dictate growth, response to therapy and
      resistance of residual malignant B cells to therapeutic agents. This minimal
      residual disease (MRD) remains a major challenge in the treatment of B-cell
      malignancies and contributes to subsequent disease relapse. B-cell receptor (BCR)
      signaling has emerged as essential mediator of B-cell homing, survival and
      environment-mediated drug resistance (EMDR). Central to EMDR are chemokine- and
      integrin-mediated interactions between lymphoma and the TME. Further, stromal
      cell-B cell adhesion confers a sustained BCR signaling leading to chemokine and
      integrin activation. Recently, the inhibitors of BCR signaling have garnered a
      substantial clinical interest because of their effectiveness in B-cell disorders.
      The efficacy of these agents is, at least in part, attributed to attenuation of
      BCR-dependent lymphoma-TME interactions. In this review, we discuss the pivotal
      role of BCR signaling in the integration of intrinsic and extrinsic determinants
      of TME-mediated lymphoma survival and drug resistance. 

PMID- 24037529
TI  - PTEN ablation in Ras(Ha)/Fos skin carcinogenesis invokes p53-dependent p21 to
      delay conversion while p53-independent p21 limits progression via cyclin D1/E2
      inhibition.
AB  - To investigate tumour progression mechanism in transgenic mouse skin
      carcinogenesis, inducible PTEN ablation (Delta5PTEN(flx)) was targeted to the
      epidermis of mice expressing activated ras(Ha)/fos oncogenes (HK1.ras and
      HK1.fos). RU486-treated HK1.ras/fos-Delta5PTEN(flx) epidermis exhibited
      significant keratinocyte proliferation resulting in hyperplasia and proliferating
      cysts. While HK1.ras/fos-Delta5PTEN(flx) papillomatogenesis was accelerated,
      malignant conversion was delayed and tumours exhibited well-differentiated
      squamous cell carcinoma (wdSCC) histotypes, suggesting inhibition of early-stage
      malignant progression. Immediate elevated p53/p21 expression was observed in
      HK1.ras/fos-Delta5PTEN(flx) hyperplasia, cysts and papillomas, and while
      malignant conversion required p53 loss, elevated p21 expression persisted in most
      wdSCCs to limit further progression, unless p21 was also lost and wdSCC
      progressed to more aggressive carcinomas. In contrast, TPA-promoted (that is, c
      fos-activated) bi-genic HK1.ras-Delta5PTEN(flx) cohorts lost p53/p21 expression
      during early papillomatogenesis and rapidly produced poorly differentiated
      carcinomas (pdSCCs) with high BrdU-labelling and elevated cyclin D1/E2 expression
      levels, indicative of a progression mechanism driven by failures in cell-cycle
      control. Intriguingly, HK1.ras/fos-Delta5PTEN(flx) wdSCCs did not exhibit similar
      failures, as western and immunofluorescence analysis found downregulated cyclin
      E2 whenever p21 persisted; further, while westerns detected elevated cyclin D1,
      immunofluorescence identified reduced expression in proliferative basal layer
      nuclei and a redistributed expression profile throughout p21-positive wdSCC
      keratinocytes. These data demonstrate that rapid early epidermal responses to
      ras(Ha)/fos/DeltaPTEN co-operation involve induction of p53/p21 to alter
      differentiation and divert excessive proliferation into cyst formation. Further,
      despite three potent oncogenic insults p53 loss was required for malignant
      conversion, and following p53 loss persistent, p53-independent p21 expression
      possessed the potency to limit early-stage malignant progression via cyclin D1/E2
      inhibition. 

PMID- 24037530
TI  - miR-93-directed downregulation of DAB2 defines a novel oncogenic pathway in lung
      cancer.
AB  - The disabled homolog 2 (DAB2) gene was recently identified as a tumor suppressor
      gene with its expression downregulated in multiple cancer types. The role of DAB2
      in lung tumorigenesis, however, is not fully characterized, and the mechanisms of
      DAB2 dysregulation in lung cancer are not defined. Here we show that low DAB2
      levels in lung tumor specimens are significantly correlated with poor patient
      survival, and that DAB2 overexpression significantly inhibits cell growth in
      cultured lung cancer cells, indicating its potent tumor suppressor function. We
      next identify that microRNA miR-93 functions as a potent repressor of DAB2
      expression by directly targeting the 3'UTR of the DAB2 mRNA. Using in vitro and
      in vivo approaches, we demonstrate that miR-93 overexpression has an important
      role in promoting lung cancer cell growth, and that its oncogenic function is
      primarily mediated by downregulating DAB2 expression. Our clinical investigations
      further indicate that high tumor levels of miR-93 are correlated with poor
      survival of lung cancer patients. The correlations of both low DAB2 and high miR
      93 expression levels with poor patient survival strongly support the critical
      role of the miR-93/DAB2 pathway in determining lung cancer progression. 

PMID- 24037531
TI  - Androgen receptor and microRNA-21 axis downregulates transforming growth factor
      beta receptor II (TGFBR2) expression in prostate cancer.
AB  - Prostate cancer cells escape growth inhibition from transforming growth factor
      beta (TGFbeta) by downregulating TGFbeta receptors. However, the mechanism by
      which cancer cells downregulate TGFbeta receptors in prostate is not clear. Here,
      we showed that coordinated action of miR-21 and androgen receptor (AR) signaling
      had a critical role in inhibiting TGFbeta receptor II (TGFBR2) expression in
      prostate cancer cells. Our results revealed that miR-21 suppresses TGFBR2 levels
      by binding to its 3'-UTR and AR signaling further potentiates this effect in both
      untransformed and transformed human prostate epithelial cells as well as in human
      prostate cancers. Analysis of primary prostate cancers showed that increased miR
      21/AR expression parallel a significantly reduced expression of TGFBR2.
      Manipulation of androgen signaling or the expression levels of AR or miR-21
      negatively altered TGFBR2 expression in untransformed and transformed human
      prostate epithelial cells, human prostate cancer xenografts and mouse prostate
      glands. Importantly, we demonstrated that miR-21 and AR regulated each other's
      expression resulting in a positive feedback loop. Our results indicated that miR
      21/AR mediate its tumor-promoting function by attenuating TGFbeta-mediated
      Smad2/3 activation, cell growth inhibition, cell migration and apoptosis.
      Together, these results suggest that the AR and miR-21 axis exerts its oncogenic
      effects in prostate tumors by downregulating TGFBR2, hence inhibiting the tumor
      suppressive activity of TGFbeta pathway. Targeting miR-21 alone or in combination
      with AR may restore the tumor inhibitory activity of TGFbeta in prostate cancer. 

PMID- 24037533
TI  - Predictive biomarkers for cancer therapy with PARP inhibitors.
AB  - Poly(ADP-ribose) polymerase (PARP) inhibitors have raised high expectations for
      the treatment of multiple malignancies. PARP inhibitors, which can be used as
      monotherapies or in combination with DNA-damaging agents, are particularly
      efficient against tumors with defects in DNA repair mechanisms, in particular the
      homologous recombination pathway, for instance due to BRCA mutations. Thus,
      deficient DNA repair provides a framework for the success of PARP inhibitors in
      medical oncology. Here, we review encouraging results obtained in recent clinical
      trials investigating the safety and efficacy of PARP inhibitors as anticancer
      agents. We discuss emerging mechanisms of regulation of homologous recombination
      and how inhibition of DNA repair might be used in cancer therapy. We surmise that
      the identification of patients that are likely to benefit from PARP inhibition
      will improve the clinical use of PARP inhibitors in a defined target population.
      Thus, we will place special emphasis on biomarker discovery.

PMID- 24037534
TI  - Effect of diagnostic predictions combined with clinical information on avoiding
      perceptual errors of computed tomography.
AB  - PURPOSE: We hypothesized that even with appropriate clinical information,
      abnormal CT findings can still be missed if correct diagnostic predictions are
      not made. MATERIALS AND METHODS: Of 388 total students (97 5th-year medical
      students * 4), students who detected abnormalities without clinical information
      were eliminated. The remaining students (hereafter, subjects) obtained clinical
      information, made diagnostic predictions, and reevaluated images. The proportion
      of failures in detecting abnormalities was compared between the correct
      prediction group and the incorrect prediction group. In the correct prediction
      group, the relationship between failures of detection and the ranking of the
      correct diagnosis was also examined. RESULTS: A total of 341 subjects were
      assessed. The proportion of subjects who failed to detect abnormalities in the
      correct prediction group (47.7 %, 93/195) was significantly lower (P < 0.001)
      than in the incorrect prediction group (85.6 %, 125/146). In the correct
      prediction group, the proportion of subjects who failed to detect abnormalities
      was significantly lower (P = 0.004) when the correct diagnosis was ranked first
      (38.5 %, 42/109) compared with lower rankings (59.3 %, 51/86). CONCLUSION: Making
      appropriate diagnostic predictions and estimating the possibility of them based
      on clinical information is important to avoid missing abnormal CT findings.

PMID- 24037535
TI  - NMR based solvent exchange experiments to understand the conformational
      preference of intrinsically disordered proteins using FG-nucleoporin peptide as a
      model.
AB  - The conformational preference of a peptide with three phenylalanine-glycine (FG)
      repeats from the intrinsically disordered domain of nucleoporin 159 (nup159) from
      the yeast nucleopore complex is studied. Conformational states of this FG-peptide
      in dimethyl sulfoxide (DMSO), a non-native solvent, are first studied. A solvent
      exchange scheme is designed and performed to understand how the conformational
      preferences of the peptide are altered as the solvent shifts from DMSO to water.
      An ensemble of structures of a 19-residue peptide is determined based on
      (13)Calpha, (1)Halpha, and (1)HN chemical shifts and with inter-proton distances.
      An experimental model is then presented where chemical shifts and amide-proton
      temperature dependence is probed at changing DMSO to water ratios. These co
      solvent experiments provide evidence of a conformational change as the fraction
      of water increases by the stark change in the behavior of amide protons under
      varied temperature. This investigation provides a NMR based experimental method
      in the field of intrinsically disordered proteins to realize conformational
      transitions from a non-native set of structures (in DMSO) to a native set of
      disordered conformers (in water).

PMID- 24037536
TI  - Ontogenetic analysis of behavior in the tail suspension test: temporal
      differences in the emergence of within- and between-session habituation in Swiss
      mice.
AB  - Habituation is an important tool in the investigation of learning/memory
      throughout life. Despite that, few studies describe habituation from an
      ontogenetic perspective. Considering that, as soon as they are born, rodents can
      twist their bodies when lifted by their tails in an attempt to escape, this
      behavior should be well suited to study habituation behavior from birth to
      adulthood. Here, we implement a tail suspension test to study the ontogenetic
      development of habituation in Swiss mice. Our data indicate that a continuous
      within-session decrease in trunk movements can be observed from postnatal day (P)
      10 onwards and that between-sessions habituation (from one day to another) can be
      observed from P16 onwards. Furthermore, we show that the adult pattern of within-
      and between-sessions reductions in activity is already present by the beginning
      of adolescence, at P28. Our results indicate that between-sessions habituation
      involves a more complex mechanism of memory and learning than within-session
      habituation, requiring a longer period of brain maturation before it can be
      displayed.

PMID- 24037532
TI  - Rho guanine nucleotide exchange factors: regulators of Rho GTPase activity in
      development and disease.
AB  - The aberrant activity of Ras homologous (Rho) family small GTPases (20 human
      members) has been implicated in cancer and other human diseases. However, in
      contrast to the direct mutational activation of Ras found in cancer and
      developmental disorders, Rho GTPases are activated most commonly in disease by
      indirect mechanisms. One prevalent mechanism involves aberrant Rho activation via
      the deregulated expression and/or activity of Rho family guanine nucleotide
      exchange factors (RhoGEFs). RhoGEFs promote formation of the active GTP-bound
      state of Rho GTPases. The largest family of RhoGEFs is comprised of the Dbl
      family RhoGEFs with 70 human members. The multitude of RhoGEFs that activate a
      single Rho GTPase reflects the very specific role of each RhoGEF in controlling
      distinct signaling mechanisms involved in Rho activation. In this review, we
      summarize the role of Dbl RhoGEFs in development and disease, with a focus on
      Ect2 (epithelial cell transforming squence 2), Tiam1 (T-cell lymphoma invasion
      and metastasis 1), Vav and P-Rex1/2 (PtdIns(3,4,5)P3 (phosphatidylinositol
      (3,4,5)-triphosphate)-dependent Rac exchanger). 

PMID- 24037537
TI  - Comparative confocal microscopy of internal genitalia of phytoptine mites
      (Eriophyoidea, Phytoptidae): new generic diagnoses reflecting host-plant
      associations.
AB  - Confocal laser scanning microscopy (CLSM) methods are still rarely used by
      acarologists although they are very appropriate for studying minute arthropod
      pests, especially eriophyoid mites. In this paper, the female reproductive system
      of phytoptines, including the bud mite Phytoptus avellanae, the well-known pest
      of hazelnut, was studied using CLSM and resulted in new interpretations of the
      functioning anatomy of phytoptid genitalia. Comparison of cuticle-lined internal
      genitalia, based on novel CLSM-based 2D and 3D imaging, and multivariate analysis
      of morphometric measurements, show that two basic types of internal genitalia can
      be found within Phytoptinae: one type in phytoptines associated with
      monocotyledoneous hosts (especially Cyperaceae and Asparagaceae), and another one
      in those associated with various dicotyledoneous hosts. Phytoptines from monocots
      (genera Oziella and Acathrix and Phytoptus "caricis" sp. group) possess a
      spherical distal part of the spermathecal tube and a semitriangular transverse
      genital apodeme, whereas phytoptines from dicots (genus Phytoptus "avellenae" sp.
      group) possess an elongate distal part of the tube and a trapezoidal apodeme.
      These differences in the internal genitalic anatomy were used for modifying the
      diagnosis of phytoptine genera (Phytoptus, Oziella and Acathrix), and
      reorganizing the Phytoptinae, resulting in new synonymies: 11 species were
      transferred from genus Phytoptus "caricis" sp. group to the genus Oziella.

PMID- 24037538
TI  - The occupation of intestinal epithelium by Trichinella spiralis in BALB/C mice is
      not associated with local manifestation of apoptosis related factors.
AB  - Trichinella spiralis actively passes through the epithelial cells of the
      intestinal mucosa but morphologically, these cells do not manifest apparent
      damage. The possible activation of apoptotic mechanisms in the small intestine
      mucosa after infection with larvae and adults of Trichinella spiralis was
      explored by immunohistochemistry. Sporadic individual cells of normal intestinal
      epithelium showed activation of caspase-3, increased expression AIF, or Bax. The
      larval stage of intestinal trichinellosis was characterized by distortion of
      cells on the villus tips that were strongly reactive to caspase-3, Bax, and
      survivin antibodies. There was a transient loss of the survivin expression on the
      brush border of the epithelial cells at 15-h post infection, which reappeared on
      the fifth day. Bcl-2 changed its normal apical distribution and re-localized to
      the basal part of the epithelial cells. No significant changes of expression of
      the selected apoptosis-related proteins were observed in the intestinal
      epithelial cells immediately surrounding the worms. The presence of Trichinella
      affects intestinal epithelial cells, but unlike in muscle cells, invading them
      does not initiate apoptotic factors activation. 

PMID- 24037539
TI  - Protective effects of oral immunization with live Lactococcus lactis expressing
      Eimeria tenella 3-1E protein.
AB  - The codon-optimized Eimeria tenella 3-1E gene was introduced into the lactic acid
      bacterial vector pTX8048 to construct plasmid pTX8048-3-1E. The plasmid pTX8048-3
      1E was transformed into Lactococcus lactis NZ9000 by electroporation to create
      the strain of L. lactis pTX8048-3-1E. The expression of objective protein was
      verified by Western blot. The live bacteria L. lactis pTX8048-3-1E were
      administered orally, and an animal challenge experiment was carried out to
      evaluate the protective efficacy. The results indicated the strain of L. lactis
      pTX8048-3-1E was constructed successfully. Oral immunization to specific pathogen
      free (SPF) chickens with L. lactis pTX8048-3-1E provided partial protection
      against homologous challenge including significant increased oocyst decrease
      ratio, reduced average lesion score in cecum, and improved body weight gain
      compared to control bacteria L. lactis pTX8048. These results demonstrate the use
      of Lactococcus as live vector for delivery of Eimeria antigen is feasible and
      promising method to control coccidiosis in poultry. 

PMID- 24037541
TI  - Perceived barriers and enablers to referrals to community-based hospice
      palliative care volunteer programs in Canada.
AB  - Two separate studies were conducted to identify perceived barriers and enablers
      to referrals to community-based hospice palliative care volunteer programs in 2
      Atlantic Canadian provinces. In study 1, a physician, home support nurse manager,
      social worker, and volunteer coordinator (VC) were interviewed. More barriers
      than enablers were identified. Based on these results and a review of the
      literature, a "Perceived Barriers and Enablers to Hospice Palliative Care
      Volunteer Referrals Questionnaire" (PBEQ) was developed. In study 2, a total of
      10 VCs completed the PBEQ and (1) rated the extent to which they perceived 18
      items to be barriers to referrals; (2) rated the extent to which they perceived
      12 items to be enablers to referrals; and (3) described additional barriers and
      enablers. A Tips for Referrals sheet was created. 

PMID- 24037540
TI  - Mitochondrial and cytosolic roles of PINK1 shape induced regulatory T-cell
      development and function.
AB  - Mutations in PTEN-induced kinase 1 (PINK1), a serine/threonine kinase linked to
      familial early-onset Parkinsonism, compromise mitochondrial integrity and
      metabolism and impair AKT signaling. As the activation of a naive T cell requires
      an AKT-dependent reorganization of a cell's metabolic machinery, we sought to
      determine if PINK1-deficient T cells lack the ability to undergo activation and
      differentiation. We show that CD4(+) T cells from PINK1 knockout mice fail to
      properly phosphorylate AKT upon activation, resulting in reduced expression of
      the IL-2 receptor subunit CD25. Following, deficient IL-2 signaling mutes the
      activation-induced increase in respiratory capacity and mitochondrial membrane
      potential. Under polarization conditions favoring the development of induced
      regulatory T cells, PINK1(-/-) T cells exhibit a reduced ability to suppress
      bystander T-cell proliferation despite normal FoxP3 expression kinetics. Our
      results describe a critical role for PINK1 in integrating extracellular signals
      with metabolic state during T-cell fate determination, and may have implications
      for the understanding of altered T-cell populations and immunity during the
      progression of active Parkinson's disease or other immunopathologies.

PMID- 24037542
TI  - Teaching communication skills to hospice teams: comparing the effectiveness of a
      communication skills laboratory with in-person, second life, and phone role
      playing.
AB  - INTRODUCTION: Communication skills are critical in hospice care but challenging
      to teach. Therefore, a hospice agency developed a communication skills laboratory
      for nurses and social workers. METHODS: Learners role-played 3 common hospice
      scenarios. The role-play modalities were in-person, Second Life, and telephone.
      Learners were scored on 4 communication aspects. RESULTS: Learners in all
      modalities rated the laboratory as very effective. However, learners in the
      Second Life and phone modality showed greater improvements from scene 1 to 3 than
      those in the in-person modality. There were no significant differences in
      improvement between the Second Life and phone modalities. CONCLUSION: Results
      support the effectiveness of this communication skills laboratory while using
      different teaching modalities and show phone and Second Life role-plays were more
      effective than an in-person role-play.

PMID- 24037543
TI  - First evidence for seasonal fluctuations in lichen- and bark-colonising fungal
      communities.
AB  - Endophytic fungal communities in leaves of deciduous trees usually undergo
      pronounced seasonal changes. We hypothesised that such compositional shifts are
      predominantly caused by annuality of the leaves and therefore less pronounced in
      fungi colonising the perennial substrates bark and corticolous lichens. To test
      this hypothesis, thalli of the foliose lichen-forming fungal species Xanthoria
      parietina and Physconia distorta, along with the adjacent bark, were sampled
      during spring and autumn at two sides of a single tree in southern Germany.
      Analysis of clone libraries by restriction fragment length polymorphism (RFLP)
      revealed 588 singleton and 221 non-singleton RFLP-types of non-lichenised fungi.
      The communities differed significantly between host lichen species. Season and
      exposure had only a significant impact when the two factors were combined in the
      analysis. Accordingly, bark- and/or the lichen-associated fungal communities
      change throughout the year's course, a finding that rejects the initial
      hypothesis. This survey revealed valuable information for future broad-based
      studies, by indicating that a relatively high diversity of non-lichenised fungi
      is associated with corticolous lichen thalli and the adjacent bark. Furthermore,
      the structure of non-lichenised fungal assemblages associated with corticolous
      lichen communities obviously depends at least on the following factors: 'lichen
      species', 'exposure', and 'season'. 

PMID- 24037546
TI  - Covalent trapping and bacterial resistance to ceftazidime.

PMID- 24037547
TI  - Juvenile versus adult-onset ankylosing spondylitis -- clinical, radiographic, and
      social outcomes. a systematic review.
AB  - Ankylosing spondylitis (AS) has 2 main modes of onset: juvenile-onset AS (JoAS)
      and adult-onset AS (AoAS). It is not known whether JoAS is a subtype of AS, or AS
      modulated by early age of onset and longer disease duration. We performed a
      systematic review of the literature, identifying 12 articles and 1 abstract
      directly comparing JoAS and AoAS cohorts, with observational study design.
      Patients with JoAS appear to have more peripheral joint involvement both
      clinically and radiographically (especially knees and ankles) and more root joint
      involvement (hips and shoulders); they are more likely to proceed to hip
      arthroplasty and often initially present with peripheral rather than axial
      symptoms. Patients with AoAS appear to have more axial symptoms and radiographic
      disease, particularly in the lumbar spine, and worse axial metrology. In terms of
      other characteristics, more evidence is needed to confidently state whether JoAS
      and AoAS are different. 

PMID- 24037548
TI  - Low levels of antibodies against oxidized but not nonoxidized cardiolipin and
      phosphatidylserine are associated with atherosclerotic plaques in systemic lupus
      erythematosus.
AB  - OBJECTIVE: We have reported that the prevalence of atherosclerotic plaques and
      their echolucency was increased in systemic lupus erythematosus (SLE). We here
      study antibodies against oxidized cardiolipin (anti-OxCL) and phosphatidylserine
      (anti-OxPS) in SLE and in relation to atherosclerosis measures. METHODS: Patients
      with SLE (n = 114) were compared with age- and sex-matched population-based
      controls (n = 122). Common carotid intima-media thickness and plaque occurrence
      were determined by B-mode ultrasonography. Plaques were graded according to
      echogenicity as 1-4, with 1 being echolucent. Antibodies were determined by
      ELISA. RESULTS: In the SLE group, the prevalence of low IgM anti-OxPS and low
      total IgM levels (below 33rd percentile) was increased compared to controls (p =
      0.045 and p = 0.0079, respectively). Among SLE patients with atherosclerotic
      plaques, the prevalence of low IgM anti-OxPS (p = 0.0019) and anti-OxCL (p =
      0.031) was increased. Only IgM anti-OxPS remained significant (p = 0.019) after
      adjusting for other significant factors. Echolucent plaques (total, or left side)
      were more prevalent among SLE patients with low IgM anti-OxCL and anti-OxPS when
      controlled for other significant factors (p < 0.05). Low total IgM was
      independently associated with echolucent plaque on left side (p < 0.05), but not
      other atherosclerosis measures. IgM anticardiolipin antibodies (aCL) and
      antiphosphatidylserine antibodies (anti-PS) were higher among SLE patients with
      cardiopulmonary disease, including arterial, valvular, and venous disease (p <
      0.05). There were no associations between antibodies and other disease
      manifestations or activity. Both anti-OxCL and anti-OxPS, in contrast to aCL, and
      anti-PS, were cofactor-beta2-glycoprotein I (beta2-GPI)-independent. CONCLUSION:
      The prevalence of low levels of IgM anti-OxCL and anti-OxPS (both cofactor-beta2
      GPI-independent) is associated with the presence of plaques and echolucent
      plaques in SLE.

PMID- 24037549
TI  - Interferon-alpha abrogates the suppressive effect of apoptotic cells on dendritic
      cells in an in vitro model of systemic lupus erythematosus pathogenesis.
AB  - OBJECTIVE: An increased incidence of apoptotic cells and an increased activation
      of dendritic cells (DC) may be involved in the pathogenesis of systemic lupus
      erythematosus (SLE). We investigated the characteristics of apoptotic neutrophils
      and monocyte-derived DC of patients with SLE, their interaction, and the
      influence of autoantibodies and inflammatory cytokines on this interaction.
      METHODS: Kinetics of neutrophil apoptosis and DC activation were studied by flow
      cytometry. To analyze the interaction of apoptotic cells with phagocytes,
      crossover coculture experiments were performed with DC from patients with SLE and
      apoptotic Jurkat T cells as well as with apoptotic neutrophils from patients with
      SLE and the monocytic cell line U937. SLE serum and cytokines were added to this
      coculture, and activation and suppression of DC were quantified by levels of
      inflammatory cytokine secretion. RESULTS: Apoptotic neutrophils and DC from
      patients with SLE showed no inherent defects compared to healthy controls, and
      the suppressive nature of their interaction was not affected. Autoantibodies as
      well as the inflammatory cytokines interleukin 17 (IL-17) and IL-1beta had no
      influence on the interaction in this setup. Interferon (IFN)-alpha, however,
      substantially reduced the suppressive effect of apoptotic cells on DC.
      CONCLUSION: The data suggest that aberrant immune reactivity in SLE is not
      generally due to an intrinsic defect in apoptotic cells, their processing, or
      their interaction with DC, but likely arises from the milieu in which this
      interaction takes place. Our study highlights the importance of IFN-alpha during
      early stages of SLE and its potential as a therapeutic target.

PMID- 24037550
TI  - Herpes zoster vaccination in SLE: a pilot study of immunogenicity.
AB  - OBJECTIVE: Patients with systemic lupus erythematosus (SLE) are at increased risk
      of herpes zoster (HZ). Although a vaccine for HZ has been approved by the US Food
      and Drug Administration, its use in immunocompromised individuals remains
      controversial because it is a live-attenuated virus vaccine. We performed a pilot
      study of the immunogenicity of the HZ vaccine (Zostavax) in patients with SLE.
      METHODS: Ten patients with SLE and 10 control subjects >= age 50 years
      participated in this open-label vaccination study. All were seropositive for
      varicella zoster virus (VZV). Patients with SLE were excluded for SLE Disease
      Activity Index (SLEDAI) > 4, or use of mycophenolate mofetil, cyclophosphamide,
      biologics, or > 10 mg prednisone daily. Followup visits occurred at 2, 6, and 12
      weeks. Clinical outcomes included the development of adverse events, particularly
      HZ or vesicular lesions, and SLE flare. Immunogenicity was assessed with VZV
      specific interferon-gamma-producing enzyme-linked immunospot (ELISPOT) assays and
      with antibody concentrations. RESULTS: All subjects were women. Patients with SLE
      were slightly older than controls (60.5 vs 55.3 yrs, p < 0.05). Median baseline
      SLEDAI was 0 (range 0-2) for patients with SLE. No episodes of HZ, vesicular
      rash, serious adverse events, or SLE flares occurred. Three injection site
      reactions occurred in each group: mild erythema or tenderness. The proportion of
      subjects with a > 50% increase in ELISPOT results following vaccination was
      comparable between both groups, although absolute SLE responses were lower than
      controls. Antibody titers increased only among controls following vaccination (p
      < 0.05). CONCLUSION: The HZ vaccination yielded a measurable immune response in
      this cohort of patients with mild SLE taking mild-moderate immunosuppressive
      medications. No herpetiform lesions or SLE flares were seen in this small cohort
      of patients. ClinicalTrials.gov ID:NCT01474720.

PMID- 24037552
TI  - Low bone density in systemic sclerosis. A systematic review.
AB  - OBJECTIVE: The effect of systemic sclerosis (SSc) on bone density is not well
      understood. Through systematic review of the literature, the objectives of this
      study were to synthesize data about the prevalence of low bone mineral density
      (BMD), risk factors for low BMD, and occurrence of fracture and fracture-related
      mortality in SSc. METHODS: A search was conducted of MEDLINE (1948-2012),
      Evidence Based Medicine Reviews (1991-2012), EMBASE (1980-2012), and CINAHL (1981
      2012). Abstracts were screened to identify studies that evaluated low BMD in
      patients with SSc. Two investigators independently used a standardized form to
      abstract prevalence of osteopenia and osteoporosis (OP); risk factors for low
      BMD, BMD measurements, frequency of fracture, and fracture-related mortality.
      RESULTS: Screening of 1032 citations identified 19 articles. Fifteen studies
      compared patients with SSc to controls. Most patients were white, female
      (prevalence 74%-100%), and postmenopausal (prevalence 45.9%-100%). The prevalence
      of low BMD and OP was 27%-53.3% and 3%-51.1%, respectively. Ten studies reported
      a lower BMD in patients with SSc compared to matched controls, whereas 2 studies
      reported no difference. Candidate risk factors for low BMD in SSc include family
      history of OP, age, menopause, diffuse subtype, presence of internal organ
      involvement, low vitamin D levels, and calcinosis. However, the studies
      supporting these factors were conflicting. Fracture rate ranged between 0% and
      38%. No study reported OP-related fracture mortality. CONCLUSION: The data
      suggest that patients with SSc are at risk of low BMD and fracture, especially
      when other risk factors for OP are present. The interaction of SSc
      manifestations, traditional OP risk factors, and clinically relevant outcomes is
      complex and warrants further research.

PMID- 24037551
TI  - Orthopedic surgery in rheumatoid arthritis in the era of biologic therapy.
AB  - OBJECTIVE: To analyze sociodemographic and clinic-related factors associated with
      the use of orthopedic surgical procedures in rheumatoid arthritis (RA), focusing
      on the potential role of new biologic therapies. METHODS: A retrospective medical
      record review was performed in a probability sample of 1272 patients with RA from
      47 units distributed in 19 Spanish regions. Sociodemographic and clinical
      features, use of drugs, and arthritis-related joint surgeries were recorded
      following a standardized protocol. RESULTS: A total of 94 patients (7.4%)
      underwent any orthopedic surgery during their disease course, with a total of 114
      surgeries; 47 (41.2%) of these surgeries were total joint replacement (TJR). The
      median time to first orthopedic procedure was 7.9 years from the onset of RA
      symptoms, and the rate of orthopedic surgery (excluding TJR) was 4.5 procedures
      per 100 person-years from the beginning of RA, while the rate of TJR was 2.25
      interventions per 100 person-years. A higher risk of undergoing an orthopedic
      surgical procedure was associated with taking nonsteroidal antiinflammatory drugs
      (NSAID) in the previous 2 years, female sex, longterm disease, and the presence
      of extraarticular complications. The risk factors for undergoing a TJR were being
      old, having a longterm disease, and taking biologic therapies. CONCLUSION: In the
      era of biologics, our national audit found a low percentage of patients who
      underwent orthopedic surgery, probably reflecting a thorough management of the
      RA. Sociodemographic factors, longterm RA, extraarticular complications, and
      NSAID were associated with orthopedic surgery.

PMID- 24037553
TI  - Aberrant CpG islands' hypermethylation of ABCB1 in mesenchymal stem cells of
      patients with steroid-associated osteonecrosis.
AB  - OBJECTIVE: Patients carrying an ABCB1 polymorphism have a higher risk of
      developing osteonecrosis of the femoral head (ONFH). We investigated whether
      aberrant dinucleotide CpG islands' hypermethylation of ABCB1 gene existed in
      mesenchymal stem cells (MSC) of patients with ONFH, which results in cell
      dysfunction. METHODS: Bone marrow was collected from the proximal femur of
      patients with glucocorticoid (GC)-associated ONFH (n = 22) and patients with new
      femoral neck fractures (n = 25). MSC were isolated by density gradient
      centrifugation. We investigated cell viability, intracellular reactive oxygen
      species (ROS) level, mitochondrial membrane potential (MMP), the amount of P
      glycoprotein (P-gp) and ABCB1 transcripts, and methylation at CpG islands of
      ABCB1 promoter from both the femoral neck fractures group and the GC-associated
      ONFH group treated with or without the DNA methyltransferase inhibitor, 5'-Aza-2
      deoxycytidine (5'-Aza-dC). RESULTS: We observed that MSC from GC-associated ONFH
      groups showed reduced proliferation ability, elevated ROS levels, and depressed
      MMP when compared with the other 2 groups. Low levels of P-gp and ABCB1
      transcript, as well as ABCB1 gene hypermethylation, in patients with GC
      associated ONFH were also noted. Treatment with 5'-Aza-dC rapidly restored ABCB1
      expression. Analysis of general expression revealed that aberrant CpG islands'
      hypermethylation of ABCB1 caused sensitivity to GC and induced changes in the
      proliferation and oxidative stress of MSC under GC administration. CONCLUSION:
      These data suggest that aberrant CpG islands' hypermethylation of ABCB1 gene may
      be responsible for individual differences in the development of GC-associated
      ONFH.

PMID- 24037554
TI  - Determining best practices in early rheumatoid arthritis by comparing differences
      in treatment at sites in the Canadian Early Arthritis Cohort.
AB  - OBJECTIVE: To determine site variation by comparing outcomes across sites in an
      early rheumatoid arthritis cohort. METHODS: Sites from the Canadian Early
      Arthritis Cohort database with at least 40 patients were studied. Comparisons
      were made among sites in change in 28-joint Disease Activity Score (DAS28),
      proportion of patients in DAS28 remission, and treatment strategies. RESULTS: The
      study included 1138 baseline patients at 8 sites, with baseline (SD) age 52 years
      (16.9); 72% women; 23% erosions; 54% ever smokers; 51% rheumatoid factor
      positive; 37% anticitrullinated protein antibody-positive; disease duration 187
      (203) days; DAS28 4.5 (1.4). Site had an effect on outcomes when adjusting for
      confounders. At 6 and 12 months, sites B and H, the 2 largest sites, had the best
      changes in DAS28 (-1.82 and -2.09, respectively, at 6 mos, and -2.27 for both at
      12 mos; p < 0.001). Site H had the most patients in DAS28 remission at 6 months
      [64.5% compared to other sites that had from 34.1% to 51.7% (p < 0.001)], and at
      the last followup, sites B and H had the most in remission. Subcutaneous
      methotrexate was used more overall and earlier at sites B and H. Those sites used
      less steroid therapy, and site B had the second-highest use of triple disease
      modifying antirheumatic drugs at any visit. Medications were increased more in 2
      of the 3 smallest sites. Biologics were used by 9 months most in the smallest
      (50.0%) and then largest (19.6%) sites. CONCLUSION: Sites in an early
      inflammatory arthritis cohort yielded different outcomes. Better outcomes up to
      12 months may result from initial treatment with early combination therapy and/or
      subcutaneous methotrexate.

PMID- 24037555
TI  - High prevalence of metabolic syndrome in Takayasu arteritis: increased
      cardiovascular risk and lower adiponectin serum levels.
AB  - OBJECTIVE: The prevalence of metabolic syndrome (MetS) tends to be high among
      rheumatic patients, and cardiovascular disease is the leading cause of death in
      these conditions. We aimed to determine the prevalence of MetS in patients with
      Takayasu arteritis (TA) and its association with risk factors and adipokine and
      cytokine levels. METHODS: A cross-sectional study was conducted in 45 consecutive
      women with TA and 47 healthy controls matched by age and body mass index.
      RESULTS: The prevalence of MetS (International Diabetes Federation/American Heart
      Association criteria) was higher in TA compared to controls (33.34 vs 8.51%, p =
      0.003). Patients with TA had a higher frequency of hypertension (p < 0.001) and
      dyslipidemia (p = 0.001) and higher levels of insulin (p = 0.021), homeostasis
      model assessment index (p = 0.024), apolipoprotein E (p = 0.029), resistin (p =
      0.018), and C-reactive protein (CRP, p < 0.001) compared to healthy subjects,
      with similar levels of adiponectin and plasminogen activator inhibitor-1 (PAI-1;
      p > 0.05). Further analysis of patients with TA with and without MetS revealed a
      higher frequency of overweight/obesity (66.66 vs 26.66%, p = 0.022), higher
      Framingham score >= 1 (p = 0.032), and lower adiponectin levels (20.37 +/- 21.16
      vs 38.64 +/- 22.62 MUg/ml, p = 0.022) in the patients with MetS. No differences
      were found regarding disease duration, activity, glucocorticoid use, resistin,
      and PAI-1 levels in the 2 groups of patients with TA (p > 0.05). Patients with
      and without MetS showed no differences in cytokine levels [interleukin 12 (IL-12,
      IL-1a, IL-6) and tumor necrosis factor-alpha]. IL-6 had a positive Pearson
      correlation with CRP only in TA patients with MetS (r = 0.57; p = 0.050).
      CONCLUSION: A high prevalence of MetS was observed in patients with TA and this
      comorbidity seems to identify a subgroup of overweight/obese patients with high
      cardiovascular risk without a significant association with disease status.
      Further longitudinal studies are necessary to observe the effects of controlling
      this modifiable risk factor in the quality of life and survival of patients with
      TA.

PMID- 24037556
TI  - Surgical collaboration.

PMID- 24037557
TI  - Pulmonary metastasectomy in colorectal cancer.

PMID- 24037558
TI  - Systematic review and meta-analysis of population-based mortality from ruptured
      abdominal aortic aneurysm.
AB  - BACKGROUND: A substantial proportion of patients with a ruptured abdominal aortic
      aneurysm (rAAA) die outside hospital. The objective of this study was to estimate
      the total mortality, including prehospital deaths, of patients with rAAA.
      METHODS: This was a systematic review and meta-analysis following the MOOSE
      guidelines. The Embase, MEDLINE and Cochrane Library databases were searched. All
      population-based studies reporting both prehospital and in-hospital mortality in
      patients with rAAA were included. Studies were assessed for methodological
      quality and heterogeneity, and pooled estimates of mortality from rAAA were
      calculated using a random-effects model. RESULTS: From a total of 3667 studies,
      24 retrospective cohort studies, published between 1977 and 2012, met the
      inclusion criteria. The quality of included studies varied, in particular the
      method of determining prehospital deaths from rAAA. The estimated pooled total
      mortality rate was 81 (95 per cent confidence interval 78 to 83) per cent. A
      decline in mortality was observed over time (P = 0.002); the pooled estimate of
      total mortality in high-quality studies before 1990 was 86 (83 to 89) per cent,
      compared with 74 (72 to 77) per cent since 1990. Some 32 (27 to 37) per cent of
      patients with rAAA died before reaching hospital. The in-hospital non
      intervention rate was 40 (33 to 47) per cent, which also declined over the years.
      CONCLUSION: The pooled estimate of total mortality from rAAA is very high,
      although it has declined over the years. Most patients die outside hospital, and
      there is no surgical intervention in a considerable number of those who survive
      to reach hospital.

PMID- 24037559
TI  - Surgical management of disappearing colorectal liver metastases.
AB  - BACKGROUND: Owing to expanded surgical indications for colorectal liver
      metastasis (CRLM) and improved systemic therapy, hepatic surgeons are
      increasingly faced with the problem of disappearing (no longer visible on
      imaging) liver metastasis (DLM). METHODS: A review of relevant studies was
      performed. Studies that reported on DLM associated with preoperative chemotherapy
      for CRLM were identified, and data were synthesized and tabulated. The PubMed
      database was searched for relevant articles published between January 2000 and
      December 2012. RESULTS: A complete response on imaging does not necessarily
      equate with a complete clinical or pathological response. Rather, residual
      macroscopic disease is found in about 25-45 per cent of patients at the time of
      operation. Even among patients with a complete pathological response, long-term
      remission occurs in only 20-50 per cent of those treated with systemic therapy. A
      durable response of DLM is more common following the use of hepatic artery
      infusion therapy. CONCLUSION: Liver resection should include all original sites
      of disease if possible.

PMID- 24037560
TI  - Surgical management of disappearing colorectal liver metastases (Br J Surg 2013;
      100: 1414-1420).

PMID- 24037561
TI  - Systematic review and meta-analysis of the association between diabetes mellitus
      and incidence and mortality in breast and colorectal cancer.
AB  - BACKGROUND: Increasing evidence suggests that diabetes mellitus (DM) is
      associated with increased cancer incidence and mortality. Several mechanisms
      involved in diabetes, such as promotion of cell proliferation and decreased
      apoptosis, may foster carcinogenesis. This study investigated the association
      between DM and cancer incidence and cancer-specific mortality in patients with
      breast and colorectal carcinoma. METHODS: A meta-analysis of controlled trials,
      prospective cohort studies and pooled cohort studies published after 2007 was
      conducted. Embase, PubMed and the Cochrane Library were searched. Summary hazard
      ratios (HRs) were calculated using a random-effects model. Sensitivity and
      subgroup analyses were performed to adjust for confounders, mode of DM assessment
      and follow-up time. RESULTS: Twenty studies were included to investigate the
      association between DM and breast and colorectal cancer incidence and cancer
      specific mortality. The studies predominantly comprised patients with type II DM.
      The overall HR for breast cancer incidence was 1.23 (95 per cent confidence
      interval 1.12 to 1.34) and that for colorectal cancer was 1.26 (1.14 to 1.40) in
      patients with DM compared with those without diabetes. The overall HR was 1.38
      (1.20 to 1.58) for breast cancer- and 1.30 (1.15 to 1.47) for colorectal cancer
      specific mortality in patients with DM compared with those without diabetes.
      CONCLUSION: This meta-analysis indicated that DM is a risk factor for breast and
      colorectal cancer, and for cancer-specific mortality.

PMID- 24037562
TI  - Systematic review of the clinical effectiveness of neuromodulation in the
      treatment of faecal incontinence.
AB  - BACKGROUND: Over the past 18 years neuromodulation therapies have gained support
      as treatments for faecal incontinence (FI); sacral nerve stimulation (SNS) is the
      most established of these. A systematic review was performed of current evidence
      regarding the clinical effectiveness of neuromodulation treatments for FI.
      METHODS: The review adhered to the PRISMA framework. A comprehensive search of
      the literature included PubMed, MEDLINE, Embase and Evidence-Based Medicine
      Reviews. Methodological quality assessment and data extraction were completed in
      a systematic fashion. RESULTS: For SNS, 321 citations were identified initially,
      of which 61 studies were eligible for inclusion. Of studies on other
      neuromodulation techniques, 11 were eligible for review: seven on percutaneous
      tibial nerve stimulation (PTNS) and four on transcutaneous tibial nerve
      stimulation (TTNS). On intention-to-treat, the median (range) success rates for
      SNS were 63 (33-66), 58 (52-81) and 54 (50-58) per cent in the short, medium and
      long terms respectively. The success rate for PTNS was 59 per cent at the longest
      reported follow-up of 12 months. SNS, PTNS and TTNS techniques also resulted in
      improvements in Cleveland Clinic Incontinence Score and quality-of-life measures.
      Despite significant use of neuromodulation in treatment of FI, there is still no
      consensus on outcome reporting in terms of measures used, aetiologies assessed,
      length of follow-up or assessment standards. CONCLUSION: Emerging data for SNS
      suggest maintenance of its initial therapeutic effect into the long term. The
      clinical effectiveness of PTNS is comparable to that of SNS at 12 months,
      although there is no evidence to support its continued effectiveness after this
      period. PTNS may be a useful treatment before SNS. The clinical effectiveness of
      TTNS is still uncertain owing to the paucity of available evidence. A consensus
      to standardize the use of outcome measures is recommended in order that further
      reports can be compared meaningfully.

PMID- 24037563
TI  - Randomized trial of the effect of video feedback on the acquisition of surgical
      skills.
AB  - BACKGROUND: Constructive feedback provides a mechanism for reinforcing learning
      during the acquisition of surgical skills. Feedback is usually given verbally,
      and sometimes documented, after direct observation by a trained assessor. The aim
      was to evaluate video recording as an effective modality for enhancing feedback,
      in comparison with standard verbal feedback alone. METHODS: This was a
      prospective, blinded, randomized clinical trial comparing standard verbal
      feedback plus video with standard verbal feedback alone. Validated pro formas for
      assessment were used and quality control was performed by independent expert
      assessors. Trial participants were recorded on video performing the surgical
      skill, and returned the next day to perform the skill again following video and
      standard verbal feedback (group 1) or standard verbal feedback alone (group 2).
      RESULTS: Forty-eight participants were divided equally between the two groups.
      There was a significant improvement in the mean overall procedure score for group
      1 of 2.875 from a maximum achievable score of 20 (P = 0.003), but not for group
      2. There were significant improvements in the specific domains of instrument
      familiarity, needle handling, skin handling and accurate apposition, again all in
      group 1. The only significant improvement in group 2 was in an organized approach
      to the task, also observed in group 1. Knot-tying security deteriorated after
      feedback in group 2 but not in group 1. CONCLUSION: The addition of video
      feedback can improve the acquisition of surgical skills, and could be
      incorporated into formal surgical curricula.

PMID- 24037564
TI  - Subxiphoid pericardial window to exclude occult cardiac injury after penetrating
      thoracoabdominal trauma (Br J Surg 2013; 100: 1454-1458).

PMID- 24037565
TI  - Long-term clinical and functional outcome following treatment for Paget
      Schroetter syndrome.
AB  - BACKGROUND: Effort-related thrombosis of the axillosubclavian vein (Paget
      Schroetter syndrome, PSS) is uncommon. It tends to affect young, active
      individuals and yet consensus on management is lacking. The aim here was to
      analyse late outcomes in a series of patients treated for PSS using a standard
      protocol. METHODS: The medical records of patients treated for PSS over 16 years
      were analysed. Patients were divided into four groups according to their
      management. Clinical and functional outcomes were analysed regarding residual
      venous defects after treatment, and Disabilities of the Arm, Shoulder and Hand
      (DASH) questionnaire scores, respectively. RESULTS: Some 117 patients (52 men and
      65 women, mean age 32 years) were included. Catheter-directed thrombolysis was
      successful in 42 of 56 treated patients. Thoracic outlet decompression surgery
      was performed in 95 patients. DASH scores improved significantly in patients
      treated surgically (P < 0.001 to P = 0.009); early surgery had a better outcome
      than delayed surgery (P = 0.040). Patients who were managed conservatively showed
      no improvement (P = 0.116). Where venoplasty was necessary, it was successful in
      18 of 25 patients. A short duration of lysis (less than 24 h) increased the risk
      of rethrombosis (P = 0.020). The method of postoperative anticoagulation had no
      influence on the rate of rethrombosis. CONCLUSION: Patients treated surgically
      for PSS had better functional outcomes than those managed conservatively. Prompt
      thrombolysis and surgery was superior to delayed management with respect to
      rethrombosis and functional outcome.

PMID- 24037566
TI  - Renal function 5 years after open and endovascular aortic aneurysm repair from a
      randomized trial.
AB  - BACKGROUND: Deterioration of renal function after major vascular surgery is an
      important complication, and may vary between patients undergoing endovascular
      (EVAR) or open surgical (OR) repair of an abdominal aortic aneurysm (AAA). The
      objective was to determine the impact of OR and EVAR on renal function after 5
      years. METHODS: This was a post hoc analysis of data collected prospectively from
      the Dutch Randomized Endovascular Aneurysm Management (DREAM) trial. Five years
      after surgery, creatinine levels were available for 189 patients (94 after OR and
      95 after EVAR). The severity of renal disease was staged using the chronic kidney
      disease classification of the US National Kidney Foundation clinical guidelines.
      RESULTS: Using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
      equation, the estimated glomerular filtration rate (eGFR) for the entire group
      declined over time, with a mean(s.d.) preoperative value of 80.0(7.6) ml per min
      per 1.73 m(2) compared with 75.7(9.7) ml per min per 1.73 m(2) after 5 years
      (mean difference 4.2 (95 per cent confidence interval 3.2 to 5.3) ml per min per
      1.73 m(2) ; P < 0.001). Five years after surgery, the mean eGFR (CKD-EPI
      equation) was not significantly different between the OR and EVAR groups:
      76.3(9.3) versus 75.1(10.0) ml per min per 1.73 m(2) (mean difference 1.2 (-1.6
      to 3.9) ml per min per 1.73 m(2) ; P = 0.410). CONCLUSION: Renal function 5 years
      after OR and EVAR for AAA was similar. Neither surgical procedure accelerated the
      loss of renal function.

PMID- 24037567
TI  - Long-term outcomes after endothoracic sympathetic block at the T4 ganglion for
      upper limb hyperhidrosis.
AB  - BACKGROUND: The aim of this study was to evaluate long-term results, quality of
      life, satisfaction and compensatory sweating after endothoracic sympathetic block
      at T4 (ESB4). METHODS: Patients who underwent an ESB4 procedure for palmar or
      palmoaxillary hyperhidrosis between 2001 and 2008 were included in a prospective
      study at a university hospital. Questionnaires devised by Keller and Milanez de
      Campos were applied to evaluate disease-specific quality of life. RESULTS: A
      total of 189 patients underwent 374 ESB4 procedures. Of 174 evaluated patients,
      54 (31.0 per cent) had palmar and 120 (69.0 per cent) had palmoaxillary
      hyperhidrosis. Median follow-up was 92 months. In both groups, treatment
      successfully reduced hyperhidrosis (P < 0.001) and quality of life increased
      significantly after ESB4 (P < 0.001), remaining stable after 5 years. Overall
      satisfaction rates decreased owing to the development of compensatory sweating
      and recurrence during follow-up. Compensatory sweating affected 41 patients (23.6
      per cent), and was severe in 11 (6.7 per cent) of 163 patients at 5-year follow
      up; eight of these 11 patients had been treated for palmoaxillary sweating. The
      severity of compensatory sweating did not deteriorate with time. The severe
      recurrence rate increased to 11.0 per cent during follow-up, and was twice as
      common in patients treated for palmoaxillary sweating as in those treated for
      palmar sweating (13.2 versus 6.1 per cent respectively). Nine reoperations (5.2
      per cent) were performed for persistent sweating, recurrence or compensatory
      sweating. CONCLUSION: T4 endothoracic sympathetic clip application is safe and
      effective in patients with upper limb hyperhidrosis, with stable long-term
      improvements in quality of life.

PMID- 24037568
TI  - Lack of association between inguinal hernia and abdominal aortic aneurysm in a
      population-based male cohort.
AB  - BACKGROUND: Previous studies have reported a higher prevalence of inguinal hernia
      in patients with abdominal aortic aneurysm (AAA). The aim of this study was to
      explore the association between inguinal hernia and AAA in a large population
      based cohort of men who had screening for AAA. METHODS: A total of 18,331 men
      aged 65-76 years had ultrasound screening for AAA in the Central Region of
      Denmark from 2008 to 2010. The Danish National Patient Registry was interrogated,
      and screened men registered with an inguinal hernia from 1977 to 2011 were
      identified. The association between inguinal hernia and AAA was assessed by
      multiple logistic regression analysis. RESULTS: The prevalence of AAA was 3.3 per
      cent (601 of 18,331). A total of 2936 (16.0 per cent) of the 18,331 patients were
      registered with a diagnosis of inguinal hernia or hernia repair. Inguinal hernia
      was not associated with AAA: crude odds ratio (OR) 0.86 (95 per cent confidence
      interval 0.68 to 1.09) and adjusted OR 0.94 (0.75 to 1.20). CONCLUSION: In
      contrast to smaller patient-based studies, this large population-based study
      found no association between inguinal hernia and AAA.

PMID- 24037569
TI  - Prospective study of pain, quality of life and the economic impact of open
      inguinal hernia repair.
AB  - BACKGROUND: There are variations in quality of life (QoL) and reported risk of
      chronic pain after inguinal hernia repair. The aim of this study was to
      investigate the improvement in pain and QoL after open inguinal hernia repair,
      and the economic impact. METHODS: Patients undergoing open mesh repair of a
      primary unilateral inguinal hernia were stratified depending on preoperative
      levels of symptoms and pain. Short Form 36 (SF-36(r)) and EQ-5DTM questionnaires
      were filled in before, and at 3 and 12 months after surgery. EQ-5DTM data,
      together with information on the mean value of a quality-adjusted life-year and
      the societal cost of hernia repair, were used to calculate the monetary value of
      QoL gained and the mean return on investment. RESULTS: Of 225 patients who began
      the study, 184 completed follow-up at 12 months. Some 77.2 per cent reported
      improvement in pain and 5.4 per cent reported increased pain after surgery.
      Significant improvement in SF-36(r) scores, pain scores measured on a visual
      analogue scale (VAS), and symptoms were found in the majority of patients, even
      those with mild symptoms before surgery. For the whole group, the bodily pain
      score increased from 56.4 before surgery to 82.6 at 12 months after hernia repair
      (P < 0.050), and the VAS score decreased from a median of 4 to 0 (P < 0.050). The
      return on investment was positive for all groups of patients, including those
      with mild symptoms. CONCLUSION: QoL improves after open inguinal hernia repair,
      with a good return on investment independent of symptom severity.

PMID- 24037570
TI  - Prospective study of pain, quality of life and economic impact of open inguinal
      hernia repair (Br J Surg 2013; 100: 1483-1488).

PMID- 24037571
TI  - Relevance of [18F]fluorodeoxyglucose positron emission tomography-positive lymph
      nodes after neoadjuvant chemotherapy for squamous cell oesophageal cancer.
AB  - BACKGROUND: Several studies have examined the clinical significance of metabolic
      response in primary tumours by [(18) F]fluorodeoxyglucose positron emission
      tomography ((18) F-FDG-PET) in patients with oesophageal cancer who undergo
      neoadjuvant therapy. The relevance of the metabolic response in lymph nodes is
      unclear. METHODS: Consecutive patients with oesophageal cancer who underwent
      neoadjuvant chemotherapy followed by surgery were studied. (18) F-FDG-PET was
      performed before and 2-3 weeks after completion of neoadjuvant chemotherapy,
      assessing FDG uptake in primary tumours and lymph nodes considered to be
      metastatic. RESULTS: Before therapy, 156 (73.9 per cent) of 211 patients had PET
      positive nodes, of whom 89 (57.1 per cent) had no evidence of metabolic activity
      in these lymph nodes following chemotherapy. There was a significant relationship
      between post-treatment lymph node status assessed by FDG-PET and numbers of
      pathologically confirmed metastatic lymph nodes. Patients with post-treatment PET
      positive nodes had shorter survival than those without (5-year survival rate 25
      versus 62.6 per cent; P < 0.001). There was no difference in survival between
      patients with PET-positive nodes before but not after therapy and patients who
      had PET-negative nodes throughout (5-year survival rate 59 versus 71 per cent
      respectively; P = 0.207). Multivariable analysis identified post-treatment nodal
      status assessed by FDG-PET and tumour depth as independent prognostic factors.
      CONCLUSION: Identification of PET-positive lymph nodes after completion of
      chemotherapy is a predictor of poor prognosis of patients with oesophageal cancer
      scheduled for surgery. FDG-PET lymph node status after neoadjuvant chemotherapy
      is more important than that before chemotherapy.

PMID- 24037572
TI  - In vitro effects of proteases in human pancreatic juice on stability of liquid
      and carrier-bound fibrin sealants.
AB  - BACKGROUND: Fibrin sealants are used in pancreatic surgery to prevent leakage of
      pancreatic fluid and reduce associated complications. The efficacy of this
      approach is unclear. METHODS: Fibrin clots were generated in vitro from two
      commercially available liquid fibrin sealants (Tissucol Duo(r) and Evicel(r)) and
      the carrier-bound fibrin sealant Tachosil(r), and exposed to normal saline or
      human pancreatic fluid. Stability of the sealants was assessed by release of the
      fibrin and collagen degradation products, D-dimer and hydroxyproline. The effect
      of protease inhibitors on sealant breakdown was assessed. RESULTS: Clots
      generated from liquid fibrin sealants degraded rapidly in pancreatic fluid, but
      not in normal saline. D-dimer release from fibrin clots by pancreatic fluid was
      approximately 1700 ug/ml after 24 h and less than 20 ug/ml by saline. Pancreatic
      fluid, but not normal saline, degraded both the fibrin and collagen component of
      Tachosil(r). After 6 h, mean(s.e.m.) D-dimer levels in pancreatic fluid exposed
      to Tachosil(r) were 850(183) ng/ml, compared with 60(6) ng/ml in normal saline.
      The mean(s.e.m.) hydroxyproline concentration in pancreatic fluid was 497(17)
      ug/ml after a 24-h exposure to Tachosil(r), compared with 26(12) ug/ml in normal
      saline. Protease inhibitors significantly inhibited breakdown of liquid sealants
      (D-dimer levels less than 50 ug/ml after 24 h) and Tachosil(r) (D-dimer release
      179(12) ng/ml at 6 h; hydroxyproline release 181(29) ug/ml at 24 h). CONCLUSION:
      Proteases in pancreatic juice effectively degrade both liquid and carrier-bound
      fibrin sealants in vitro. The use of these products in pancreatic surgery with
      the aim of preventing leakage of pancreatic fluid is not supported by this
      experimental study.

PMID- 24037573
TI  - Outcome after resection and radiofrequency ablation of liver metastases from
      small intestinal neuroendocrine tumours.
AB  - BACKGROUND: In patients with small intestinal neuroendocrine tumour (SI-NET),
      liver resection or radiofrequency ablation (RFA) of liver metastases is performed
      for palliation of carcinoid syndrome, and in an effort to improve survival. Data
      are generally reported from case series, and no randomized trials have studied
      these treatments. The aim was to compare outcome after liver resection and/or RFA
      with that of non-surgical treatment in patients with liver metastases from SI
      NET. METHODS: The study included patients with liver metastases from SI-NET who
      underwent liver RFA/resection or were treated non-surgically. A propensity score
      match was performed to reduce bias between groups, using baseline variables such
      as the Charlson co-morbidity index, age, symptoms, carcinoid heart disease,
      extent of metastases and proliferation index. RESULTS: Some 103 patients who had
      RFA and/or liver resection were compared with 273 controls. Propensity score
      matching resulted in two matched groups, each of 72 patients, with no significant
      differences in baseline variables. The matched resection/RFA and control groups
      showed no difference in overall survival (both 74 per cent at 5 years; P = 0.869)
      or disease-specific survival (74 versus 78 per cent respectively at 5 years; P =
      1.000). However, urinary 5-hydroxyindoleacetic acid levels were lower (median 77
      versus 120 umol per 24 h; P = 0.005) and the proportion of patients with
      progressive disease within the liver was smaller (2 of 18 versus 8 of 18; P <
      0.001) in the resection/RFA group after 5 years. CONCLUSION: These data do not
      support the use of liver resection and/or RFA in an effort to prolong survival in
      patients with liver metastases from SI-NET.

PMID- 24037574
TI  - Editor's commentary.

PMID- 24037575
TI  - Outcomes after hepatic resection and subsequent multimodal treatment of
      recurrence for multifocal hepatocellular carcinoma.
AB  - BACKGROUND: The role of liver resection in patients with multifocal
      hepatocellular carcinoma (HCC) with well preserved liver function is
      controversial. This study was conducted to evaluate the outcomes of such
      patients. METHODS: This was a retrospective analysis of patients who underwent
      liver resection for multifocal HCC between 1992 and 2011. Postoperative outcomes,
      survival and predictors of outcomes were analysed. RESULTS: Of 46 patients who
      underwent hepatic resection for multifocal HCC, 38 had Barcelona Clinic Liver
      Cancer stage B disease. Major hepatectomy was performed in 27 patients, and major
      complications occurred in nine (20 per cent). The 90-day postoperative mortality
      rate was 7 per cent. Overall 1-, 2-, 3- and 5-year survival rates were 78, 64, 59
      and 53 per cent respectively (median 70 months), whereas corresponding recurrence
      free survival rates were 53, 32, 30 and 27 per cent (median 14 months).
      Recurrence developed in 28 (61 per cent) of the 46 patients, affecting the liver
      only in 22. Three-quarters of patients with recurrence underwent further therapy.
      Major hepatectomy (hazard ratio (HR) 0.37, 95 per cent confidence interval 0.14
      to 0.95; P = 0.038), microvascular (HR 3.44, 1.35 to 8.74; P = 0.009) and
      macrovascular (HR 2.68, 1.11 to 6.43; P = 0.028) invasion, and cirrhosis (HR
      3.15, 1.12 to 8.86; P = 0.029) were associated with overall survival.
      Microvascular invasion (HR 2.81, 1.06 to 7.40; P = 0.037), cirrhosis (HR 3.12,
      1.41 to 6.88; P < 0.001) and bilobar disease (HR 2.93, 1.09 to 7.88; P = 0.033)
      were associated with recurrence-free survival. CONCLUSION: In selected patients
      with multifocal HCC and well preserved liver function, long-term survival is
      possible after liver resection and subsequent aggressive treatment of recurrence.

PMID- 24037576
TI  - Sarcopenia as a predictor of prognosis in patients following hepatectomy for
      hepatocellular carcinoma.
AB  - BACKGROUND: Sarcopenia was identified recently as a poor prognostic factor in
      patients with cancer. The present study investigated the effect of sarcopenia on
      short- and long-term outcomes following partial hepatectomy for hepatocellular
      carcinoma (HCC), and aimed to identify prognostic factors. METHODS: Data were
      collected retrospectively for all consecutive patients who underwent hepatectomy
      for HCC with curative intent between January 2004 and December 2009. Patients
      were assigned to one of two groups according to the presence or absence of
      sarcopenia, assessed by computed tomographic measurement of muscle mass at the
      level of the third lumbar vertebra. Clinicopathological, surgical outcome and
      long-term survival data were analysed. RESULTS: Sarcopenia was present in 75
      (40.3 per cent) of 186 patients, and was significantly correlated with female
      sex, lower body mass index and liver dysfunction, as indicated by abnormal serum
      albumin levels and indocyanine green retention test at 15 min values. In patients
      with, and without sarcopenia, the 5-year overall survival rate was 71 and 83.7
      per cent respectively, and the 5-year recurrence-free survival rate was 13 and
      33.2 per cent respectively. Multivariable analysis revealed that reduced skeletal
      muscle mass was predictive of an unfavourable prognosis. CONCLUSION: Sarcopenia
      was predictive of worse overall survival even when adjusted for other known
      predictors in patients with HCC after partial hepatectomy.

PMID- 24037577
TI  - Hierarchical multilevel analysis of increased caseload volume and postoperative
      outcome after elective colorectal surgery.
AB  - BACKGROUND: The study aimed to explore the impact of surgeon and institution
      volume on outcome following colorectal surgery in England using multilevel
      hierarchical analysis. METHODS: An observational study design was used. All
      patients undergoing primary elective colorectal resection between 2000 and 2008
      were included from the Hospital Episode Statistics database. Consultant surgeons
      and hospitals were divided into tertiles (low, medium and high volume) according
      to their mean annual colorectal cancer resection caseload. Outcome measures
      examined were postoperative 30-day mortality, 28-day readmission and reoperation,
      and length of stay. Hierarchical multiple regression analysis adjusted for age,
      sex, co-morbidity, social deprivation, year of surgery, operation type and
      surgical approach. RESULTS: A total of 109 261 elective cancer colorectal
      resections were included. High-volume consultant surgeons and hospitals were
      defined as performing more than 20.7 and 103.5 elective colorectal cancer
      procedures per year respectively. Consultant and hospital operative volumes
      increased throughout the study period. In hierarchical regression models, greater
      surgeon and institutional volume independently predicted only shorter length of
      hospital stay. No statistical association was observed between higher provider
      volume and postoperative mortality, 28-day reoperation or readmission rates.
      CONCLUSION: Increasing elective colorectal cancer caseload alone may have
      marginal postoperative benefit.

PMID- 24037578
TI  - Authors' reply: Randomized clinical trial of self-gripping mesh versus sutured
      mesh for Lichtenstein hernia repair (Br J Surg 2013; 100: 474-481).

PMID- 24037579
TI  - Randomized clinical trial of self-gripping mesh versus sutured mesh for
      Lichtenstein hernia repair (Br J Surg 2013; 100: 474-481).

PMID- 24037580
TI  - Systematic review and meta-analysis of the evidence for flexible sigmoidoscopy as
      a screening method for the prevention of colorectal cancer (Br J Surg 2012; 99:
      1488-1500).

PMID- 24037581
TI  - Systematic review and meta-analysis of the early and late outcomes of open and
      endovascular repair of abdominal aortic aneurysm (Br J Surg 2013; 100: 863-872).

PMID- 24037582
TI  - Author's reply: Systematic review and meta-analysis of the evidence for flexible
      sigmoidoscopy as a screening method for the prevention of colorectal cancer (Br J
      Surg 2012; 99: 1488-1500).

PMID- 24037583
TI  - Authors' reply: Systematic review and meta-analysis of the early and late
      outcomes of open and endovascular repair of abdominal aortic aneurysm (Br J Surg
      2013; 100: 863-872).

PMID- 24037584
TI  - Author's reply: Surgical delay is a critical determinant of survival in
      perforated peptic ulcer (Br J Surg 2013; 100: 1045-1049).

PMID- 24037585
TI  - Surgical delay is a critical determinant of survival in perforated peptic ulcer
      (Br J Surg 2013; 100: 1045-1049).

PMID- 24037588
TI  - Cytotoxic dihydrothiophene-condensed chromones from the marine-derived fungus
      Penicillium oxalicum.
AB  - Two new dihydrothiophene-condensed chromones and a new natural chromone, namely
      oxalicumones A-C (1-3), respectively, were isolated from a culture broth of a
      marine-derived fungus, Penicillium oxalicum. The structures of 1-3 and acetylated
      derivatives of 1 (4-7) were elucidated on the basis of spectroscopic methods and
      chemical reactions. The absolute configuration of 1 and 2 were established by
      using the modified Mosher ester method and circular dichroism data of an in situ
      formed [Rh2(OCOCF3)4] and [Mo2(OAc)4] complex. (R)-MTPA ester of 1 showed
      cytotoxicity against A375, SW-620, and HeLa carcinoma cell lines with IC50 values
      of 8.9, 7.8, and 18.4 uM, respectively. Compound 1 displayed cytotoxicity against
      A375 and SW-620 cell lines with IC50 values of 11.7 and 22.6 uM, respectively.
      The structure-biological activity relationship of 1 was discussed. 

PMID- 24037589
TI  - Mechanism of the vasodilator effect of mono-oxygenated xanthones: a structure
      activity relationship study.
AB  - The present study characterized the mechanisms involved in the vasodilator effect
      of two mono-oxygenated xanthones, 4-hydroxyxanthone and 4-methoxyxanthone. 9
      Xanthenone, the base structure of xanthones, was used for comparison. 4
      Hydroxyxanthone and 9-xanthenone induced a concentration-dependent and
      endothelium-independent vasodilator effect in arteries precontracted with
      phenylephrine (0.1 umol . L-1) or KCl (50 mmol . L-1). 4-Methoxyxanthone induced
      a concentration-dependent vasodilator effect in arteries precontracted with
      phenylephrine, which was partially endothelium-dependent, and involved production
      of nitric oxide. In endothelium-denuded arteries precontracted with KCl, the
      vasodilator effect of 4-methoxyxanthone was abolished. The vasodilator effect of
      4-hydroxyxanthone (96.22 +/- 2.10 %) and 4-methoxyxanthone (96.57 +/- 12.40 %)
      was significantly higher than observed with 9-xanthenone (53.63 +/- 8.31 %). The
      presence of an oxygenated radical in position 4 made 4-hydroxyxanthone (pIC50 =
      4.45 +/- 0.07) and 4-methoxyxanthone (pIC50 = 5.04 +/- 0.09) more potent as a
      vasodilator than 9-xanthenone (pIC50 = 3.92 +/- 0.16). In addition, 4
      methoxyxanthone was more potent than the other two xanthones. Ca2+ transients in
      vascular smooth muscle cells elicited by high K+ were abolished by 4
      hydroxyxanthone and 9-xanthenone. The endothelium-independent effect of 4
      methoxyxanthone was abolished by inhibition of K+ channels by tetraethylammonium.
      The current work shows that an oxygenated group in position 4 is essential to
      achieve Emax and to increase the potency of xanthones as vasodilators.
      Substitution of an OH by OCH3 in position 4 increases the potency of the
      vasodilator effect and changes the underling mechanism of action from the
      blockade of L-type calcium channels to an increase in NO production and
      activation of K+ channels. 

PMID- 24037590
TI  - Regulation of human pregnane X receptor and its target gene cytochrome P450 3A by
      praeruptorin A isolated from the herbal medicine Peucedanum praeruptorum.
AB  - Qianhu, the dried roots of Peucedanum praeruptorum, is a well-known traditional
      Chinese medicinal herb which was officially listed in the Chinese Pharmacopoeia.
      Praeruptorin A is the major active constituent of Qianhu. Our previous studies
      show that praeruptorin effectively transactivated the protein expression and
      catalytic activity of cytochrome P450 3A4 via the constitutive androstane
      receptor-mediated pathway. However, the effect of praeruptorin on the
      transactivation of cytochrome P450 3A4 through pregnane X receptor pathway is
      still unclear. To further elucidate the role of the pregnane X receptor pathway
      in the up-regulation of cytochrome P450 3A4 by praeruptorin, in this study, the
      effect of praeruptorin on the cytochrome P450 3A4 gene expression was
      investigated in mouse primary hepatocytes after knockdown of the pregnane X
      receptor by transient transfection of its siRNA; and the gene expression, protein
      expression, and catalytic activity of cytochrome P450 3A4 in the LS174T cells
      with pregnane X receptor overexpression were determined by real-time PCR, Western
      blot analysis, and LC-MS/MS-based cytochrome P450 3A4 substrate assay,
      respectively. We found that the level of cytochrome P450 3a11 gene expression in
      mouse primary hepatocytes was significantly increased by praeruptorin, but such
      an induction was suppressed after knockdown of pregnane X receptor by its siRNA.
      Praeruptorin significantly induced cytochrome P450 3A4 mRNA, protein expression,
      and functional activity through pregnane X receptor-mediated pathway in pregnane
      X receptor-overexpression LS174T cells; conversely, induction was not found in
      LS174T cells untransfected with pregnane X receptor plasmids. These findings
      suggest that praeruptorin can significantly up-regulate cytochrome P450 3A4 gene
      via the pregnane X receptor-mediated pathway, and this should be taken into
      consideration in potential herb-drug interactions. 

PMID- 24037591
TI  - Exposure to ethanol on prenatal days 19-20 increases ethanol intake and
      palatability in the infant rat: involvement of kappa and mu opioid receptors.
AB  - Prenatal exposure to ethanol on gestation Days 19-20, but not 17-18, increases
      ethanol acceptance in infant rats. This effect seems to be a conditioned response
      acquired prenatally, mediated by the opioid system, which could be stimulated by
      ethanol's pharmacological properties (mu-opioid receptors) or by a component of
      the amniotic fluid from gestation-day 20 (kappa-inducing factor). The latter
      option was evaluated administering non-ethanol chemosensory stimuli on gestation
      Days 19-20 and testing postnatal intake and palatability. However, prenatal
      exposure to anise or vanilla increased neither intake nor palatability of these
      tastants on postnatal Day 14. In experiment 2, the role of ethanol's
      pharmacological effect was tested by administering ethanol and selective
      antagonists of mu and kappa opioid receptors prenatally. Blocking the mu-opioid
      receptor system completely reversed the effects on intake and palatability, while
      antagonizing kappa receptors only partially reduced the effects on palatability.
      This suggests that the pharmacological effect of ethanol on the fetal mu opioid
      system is the appetitive reinforcer, which induces the prenatally conditioned
      preference detected in the preweanling period.

PMID- 24037592
TI  - Measurements of elastic modulus for human anterior lens capsule with atomic force
      microscopy: the effect of loading force.
AB  - The purpose of the study was to appraise the effect of loading force magnitude on
      the determination of the elastic modulus of the anterior lens capsule through
      atomic force microscopy. Four human anterior lens capsules taken during
      phacoemulsification cataract surgery were studied, free of epithelial cells, with
      atomic force microscopy. For the experiment, five different indentation loading
      forces were applied to near areas of the specimen. Experimental data was exported
      and analyzed according to the Hertz model to obtain the Young's modulus with
      regards to the elastic behavior of the material. Force-distance curves were
      acquired by applying a load of 2, 5, 10, 20 and 30 nN. When examining the results
      it was evident that determination of Young's modulus of the anterior lens capsule
      is dependent on the loading force concerning the examined range. Loading forces
      of 10 and 20 nN led to results without significant difference (p > 0.05) and more
      reproducible (coefficients of variation 12.4 and 11.7 %, respectively).

PMID- 24037593
TI  - Early features in acute macular neuroretinopathy.
AB  - Acute macular neuroretinopathy (AMNR) is a rare disorder characterised by acute
      onset of unilateral or bilateral visual impairment associated with reddish-brown
      wedge-shaped outer macular lesions. It is more frequently reported in young
      females and though the pathophysiology remains unclear, factors reported in
      association with its onset include post-viral illness and vasoconstrictor use. We
      report a case of AMNR in an 18-year old female patient presenting with a 2-day
      history of acute painless blurring of central vision bilaterally, following 1
      month of preceding flu-like illness. For 1 week prior to presentation, the
      patient had taken large doses of oral preparations containing phenylephrine
      hydrochloride. In addition to demonstrating characteristic optical coherence
      tomography findings seen in AMNR, we illustrate some rarely seen acute
      ophthalmoscopic features. Based on associations from this case, we add further
      insight into the pathophysiology of this condition which remains poorly
      understood.

PMID- 24037594
TI  - Testing the annual nature of speleothem banding.
AB  - Speleothem laminae have been postulated to form annually, and this lamina
      chronology is widely applied to high-resolution modern and past climate
      reconstructions. However, this argument has not been directly supported by high
      resolution dating methods. Here we present contemporary single-lamina (230)Th
      dating techniques with 2sigma precision as good as +/-0.5 yr on a laminated
      stalagmite with density couplets from Xianren Cave, China, that covers the last
      300 years. We find that the layers do not always deposit annually. Annual bands
      can be under- or over-counted by several years during different multi-decadal
      intervals. The irregular formation of missing and false bands in this example
      indicates that the assumption of annual speleothem laminae in a climate
      reconstruction should be approached carefully without a robust absolute-dated
      chronology.

PMID- 24037595
TI  - Influence of gender membership on sequential decisions of face attractiveness.
AB  - Responses in a current trial are biased by the stimulus and response in the
      preceding trial. In a mixed-category sequence, the sequential dependency is
      weaker when the stimuli of the current and preceding trials fall under different
      categories. In the present study, we investigated the influence of the gender
      membership of faces on the sequential dependency. Forty-eight pictures of male
      and female faces were presented successively. Participants rated the
      attractiveness, roundness, or intelligence of each face on a 7-point scale. The
      sequential effect was robustly observed, irrespective of the property to be
      judged. However, between-gender sequential dependency was weaker than within
      gender dependency only in the attractiveness judgment. These findings suggest
      that the gender of faces serves as a cue for forming category representations
      when face attractiveness is of interest, and hence that the formation of
      categories in sequential decisions is an adaptive process that depends on the
      property to be judged. 

PMID- 24037596
TI  - Capturing attention is not that simple: different mechanisms for stimulus-driven
      and contingent capture.
AB  - Attentional orienting can be involuntarily directed to task-irrelevant stimuli,
      but it remains unsolved whether such attentional capture is contingent on top
      down settings or could be purely stimulus-driven. We propose that attentional
      capture depends on the stimulus property because transient and static features
      are processed differently; thus, they might be modulated differently by top-down
      controls. To test this hybrid account, we adopted a spatial cuing paradigm in
      which a noninformative onset or color cue preceded an onset or color target with
      various stimulus onset asynchronies (SOAs). Results showed that the onset cue
      captured attention regardless of target type at short-but not long-SOAs. In
      contrast, the color cue captured attention at short and long SOAs, but only with
      a color target. The overall pattern of results corroborates our hypothesis,
      suggesting that different mechanisms are at work for stimulus-driven capture (by
      onset) and contingent capture (by color). Stimulus-driven capture elicits
      reflexive involuntary orienting, and contingent capture elicits voluntary feature
      based enhancement. 

PMID- 24037597
TI  - In vitro-binding of the natural siderophore enantiomers pyochelin and
      enantiopyochelin to their AraC-type regulators PchR in Pseudomonas.
AB  - The enantiomeric siderophores pyochelin and enantiopyochelin of Pseudomonas
      aeruginosa and Pseudomonas protegens promote growth under iron limitation and
      activate transcription of their biosynthesis and uptake genes via the AraC-type
      regulator PchR. Here we investigated siderophore binding to PchR in vitro using
      fluorescence spectroscopy. A fusion of the N-terminal domain of P. aeruginosa
      PchR with maltose binding protein (MBP-PchR'PAO) bound iron-loaded (ferri-)
      pyochelin with an affinity (Kd) of 41 +/- 5 MUM. By contrast, no binding occurred
      with ferri-enantiopyochelin. Stereospecificity of a similar fusion protein of the
      P. protegens PchR (MBP-PchR'CHA0) was less pronounced. The Kd's of MBP-PchR'CHA0
      for ferri-enantiopyochelin and ferri-pyochelin were 24 +/- 5 and 40 +/- 7 MUM,
      respectively. None of the proteins interacted with the iron-free siderophore
      enantiomers, suggesting that transcriptional activation by PchR occurs only when
      the respective siderophore actively procures iron to the cell.

PMID- 24037598
TI  - Cherubism.
AB  - Cherubism is one of the very few genetically determined disorders that affect
      only jaw bones. A typical form of cherubism in an 11 years old girl with features
      of bilateral swelling of the cheeks and soap bubble radiographic appearance on
      the maxilla and the mandible was presented. Multiple members of the first and
      second degree relatives were also affected. The clinical presentation of the
      case, differential diagnosis and treatment modalities were discussed.

PMID- 24037599
TI  - Calcifying epithelial odontogenic tumour with clear langerhans cells: a novel
      variant, report of a case and review of the literature.
AB  - Clear cell calcifying epithelial odontogenic tumour (CCEOT) is a rare variant of
      calcifying epithelial odontogenic tumor (CEOT). While it is not surprising to
      find clear cells in odontogenic lesions, the exact nature of the clear cells in
      CCEOT has not been elucidated. Herein, we report a case of peripheral CCEOT of
      anterior mandible in a 37 year old black female. Histologically, the tumour
      consisted of cords and small nests of clear cells surrounded by dense deposits of
      amyloid and basophilic calcifications. The cells possessed abundant clear
      cytoplasm and eccentrically located indented nuclei. Admixed with the clear cells
      were eosinophilic cuboidal to polyhedral cells. The clear cells were PAS negative
      and immunoreactive for S100 protein, CD1a and Langerin. The clear cells were
      negative for MNF-116, SMA, Desmin and CK-19. It is therefore recommended to
      recognize two variants of CCEOT, namely, CEOT with clear cell change and CEOT
      with clear Langerhans cells (LC). We further suggest that the contradictory term
      "non-calcifying variant of calcifying epithelial odontogenic tumour with LC" to
      be abandoned, as the current case clearly indicates that LC could be seen in CEOT
      irrespective of the presence or absence of calcifications. 

PMID- 24037600
TI  - Biosorption of As (III) by non-living biomass of an arsenic-hypertolerant
      Bacillus cereus strain SZ2 isolated from a gold mining environment: equilibrium
      and kinetic study.
AB  - The ability of non-living biomass of an arsenic-hypertolerant Bacillus cereus
      strain SZ2 isolated from a gold mining environment to adsorb As (III) from
      aqueous solution in batch experiments was investigated as a function of contact
      time, initial As (III) concentration, pH, temperature and biomass dosage.
      Langmuir model fitted the equilibrium data better in comparison to Freundlich
      isotherm. The maximum biosorption capacity of the sorbent, as obtained from the
      Langmuir isotherm, was 153.41 mg/g. The sorption kinetic of As (III) biosorption
      followed well the pseudo-second-order rate equation. The Fourier transform
      infrared spectroscopy analysis indicated the involvement of hydroxyl, amide and
      amine groups in As (III) biosorption process. Field emission scanning electron
      microscopy-energy dispersive X-ray analysis of the non-living B. cereus SZ2
      biomass demonstrated distinct cell morphological changes with significant amounts
      of As adsorbed onto the cells compared to non-treated cells. Desorption of 94 %
      As (III) was achieved at acidic pH 1 showing the capability of non-living biomass
      B. cereus SZ2 as potential biosorbent in removal of As (III) from arsenic
      contaminated mining effluent.

PMID- 24037602
TI  - Phobias of attachment-related inner states in the psychotherapy of adult
      survivors of childhood complex trauma.
AB  - The clinical case described in this article illustrates the value of taking into
      account the dynamics of disorganized attachment in the assessment of attachment
      related phobias (phobia of attachment and phobia of attachment loss) during the
      psychotherapy of chronically traumatized patients. These seemingly opposite
      phobias typically coexist in the same patient, appear as phobias of both inner
      states (affect phobias) and relational experiences, and are linked to dissociated
      representations of self-with-other. Theory and research on attachment
      disorganization provide a clinician-friendly conceptual framework for capturing
      both the intrapsychic (e.g., intrusive and nonintegrated mental states) and the
      relational (e.g., dramatic unsolvable dilemmas in interpersonal exchanges)
      aspects of the attachment-related phobias. The therapeutic strategy and the key
      interventions that logically follow from a case formulation based on this
      conceptual framework are examined. 

PMID- 24037603
TI  - Useful techniques for ultrasonography-guided free-hand puncture of a deep
      peripheral vein and catheter placement to obtain CT angiography.
AB  - PURPOSE: To show useful techniques for ultrasonography-guided free-hand puncture
      of a deep peripheral vein and catheter placement (UGFHCP). MATERIALS AND METHODS:
      The techniques were: favorable position of the patient's arm for puncturing the
      deep basilic vein, stable suspension of the transducer, and catheter lowering for
      advancement after successful venous puncture. During the study period, UGFHCP was
      performed for 75 of 263 patients who underwent coronary CTA. The patients were
      divided into two groups; those in the period before the development of the
      catheter lowering technique (n = 22, group A) and those after it (n = 53, group
      B). A catheter-based success rate was compared between groups A and B using
      Fisher's exact test. RESULTS: Neither cancellation of coronary CTA examination
      due to venous access trouble, nor subcutaneous leakage of contrast medium was
      seen in any of the 263 patients. There were 20 catheter-based successes and 18
      catheter-based failures in group A, and 49 catheter-based successes and 9
      catheter-based failures in group B. The catheter-based success rate was higher in
      group B, with a statistically significant difference (p = 0.001). CONCLUSION:
      UGFHCP achieved no cancellation of coronary CTA examination due to venous access
      trouble. The catheter lowering technique reduced the incidence of vessel
      perforation during catheter advancement, and increased the catheter-based success
      rate in UGFHCP.

PMID- 24037604
TI  - Novel air-injection technique to locate the medial cut end of lacerated
      canaliculus.
AB  - Locating the medial cut end of the severed canaliculus is the most difficult
      aspect of canalicular repair, especially in patients with more medial laceration,
      severe oedema, persistent errhysis and a narrow canaliculus. Irrigation is a
      widely used technique to identify the cut end; however, we found that air
      injected through the intact canaliculus with a straight needle failed to reflux
      when the common canaliculus or lacrimal sac was not blocked. We describe a
      simple, safe and efficient air-injection technique to identify the medial cut
      edge of a lacerated canaliculus. In this method, we initially submersed the
      medial canthus under normal saline, then injected filtered air through the intact
      canaliculus using a side port stainless steel probe with a closed round tip. The
      tip was designed to block the common canaliculus to form a relatively closed
      system. The efficiency of this novel air-injection technique was equivalent to
      the traditional technique but does not require the cooperation of the patient to
      blow air. Using this technique, the medial cut end was successfully identified by
      locating the air-bubble exit within minutes in 19 cases of mono-canalicular
      laceration without any complication. 

PMID- 24037605
TI  - Higher incidence of retinal pigment epithelium tears after ranibizumab in
      neovascular age-related macular degeneration with increasing pigment epithelium
      detachment height.

PMID- 24037606
TI  - Causes of certifications for severe sight impairment (blind) and sight impairment
      (partial sight) in children in England and Wales.
AB  - AIM: To explore and describe trends in the principal disorders/conditions
      ('cause') for severe sight impairment (SSI) (blind) and sight impairment (SI)
      (partial sight) certification in children in England and Wales since 1999.
      METHODS: We obtained certification data for SI and SSI from a national database
      for all individuals aged 16 years or less at the time of certification in England
      and Wales for the years 1999/2000 and for the years 2007/2008-2009/2010. RESULTS:
      In total, there were 861 certifications in the year 1999/2000, rising to 1040
      certifications in 2009/2010. The commonest single causes of SSI certification in
      1999/2000 were cerebral visual impairment (23.2%) and optic nerve disorders
      (23.2%). The commonest single causes of SI certification in the same year
      comprised nystagmus (16.7%) and optic nerve disorders (15.5%). Cerebral visual
      impairment was the commonest single cause of SSI in children in England and Wales
      annually between 2007/2008 and 2009/2010 accounting for 21%-31% of
      certifications. The commonest causes of SI certification in 2009/2010 were
      congenital globe anomalies (18.4%) and retinal dystrophy (16.6%). The proportion
      of SI and SSI due to optic nerve disorders has decreased since 1999/2000.
      CONCLUSIONS: Our findings suggest that in England and Wales, cerebral visual
      impairment is now the commonest cause of paediatric SSI certification and
      hereditary retinal dystrophy and congenital globe anomalies are the commonest
      causes of SI certification.

PMID- 24037607
TI  - Perceptual learning treatment in patients with anisometropic amblyopia: a
      neuroimaging study.
AB  - AIMS: To investigate the neuromechanisms of perceptual learning treatment in
      patients with anisometropic amblyopia using functional MRI (fMRI) and diffusion
      tensor imaging (DTI) techniques. METHODS: 20 patients with monocular
      anisometropic amblyopia participated in the study. Both fMRI and DTI data were
      acquired for each patient twice: before and after 30 days' perceptual learning
      treatment for the amblyopic eye. During fMRI scanning, patients viewed the
      stimuli with either the sound or amblyopic eye. Changes of cortical activation
      after treatment were evaluated. In the DTI exams, the fractional anisotropy (FA)
      values, apparent diffusion coefficient (ADC) values, the voxel numbers of optic
      radiations (ORs), and the number of tracks were compared between the ipsilateral
      and the contralateral ORs and also between the previous and posterior scans.
      RESULTS: Remarkable increased activation via the amblyopic eyes was found in
      Brodmann Area (BA) 17-19, bilateral temporal lobes, and right cingulate gyrus
      after the perceptual learning treatment. No significant changes were found in the
      FA values, ADC values, voxel numbers, and the number of tracks after the
      treatment. CONCLUSIONS: These results indicate that perceptual learning treatment
      for amblyopia had a positive effect on the visual cortex and temporal lobe visual
      areas in patients with anisometropic amblyopia.

PMID- 24037608
TI  - Sebaceous carcinoma in Japanese patients: clinical presentation, staging and
      outcomes.
AB  - AIM: To describe the clinical features, management and correlation of the
      American Joint Committee on Cancer tumour node metastasis (TNM) staging for
      eyelid carcinoma with outcomes in Japanese patients with sebaceous carcinoma.
      METHODS: Multicentre retrospective review of 63 Japanese patients. Tumours were
      staged using the American Joint Committee on Cancer 7th edition TNM criteria.
      RESULTS: A distinct mass was the initial presentation in 94% and correct initial
      diagnosis made in 57% patients. Most tumours (60%) presented at stage T2aN0M0.
      The remaining TNM stages were: T2bN0M0 (25%); T3aN0M0 (9%); T3bN0M0 (2%); T2bN1M0
      (2%); T3bN1M1 (2%). Frozen section controlled excision was performed in 81%. One
      patient required an orbital exenteration. Median follow-up was 4.2 years. Local
      recurrence occurred in four patients treated with frozen section controlled
      excision. Five patients had regional nodal metastases, two of which had T2aN0M0
      lesions. T3a tumours and greater were significantly associated with local
      recurrence but not regional nodal metastasis. One patient died due to disease.
      One patient is alive with disease, and remaining patients were alive without
      disease at last follow-up. CONCLUSIONS: In this Japanese cohort, an eyelid mass
      was the main clinical presentation of sebaceous carcinoma. Contrary to previous
      reports, T2a tumours smaller than 10 mm were associated with regional nodal
      metastases.

PMID- 24037609
TI  - Quality of life and cancer-related needs in patients with choroidal melanoma.
AB  - AIMS: To assess quality of life (QoL) indices and their associations with
      treatment modality, sociodemographics and cancer-related needs in choroidal
      melanoma patients. METHODS: Patients (N=99) treated at the University of
      California, Los Angeles, for choroidal melanoma within the prior 5 years (M=2.05)
      completed questionnaires assessing demographics, cancer-related needs, vision
      specific QoL, depressive symptoms and concern about recurrence. Visual acuity,
      comorbidities, treatment modality (radiotherapy, enucleation) and years since
      diagnosis were gathered from medical records. Primary analyses were multiple
      regressions. RESULTS: Although concern about cancer recurrence was elevated, QoL
      was better than in other oncology samples and comparable with healthy samples on
      some outcomes. Enucleation was associated with worse vision-specific QoL, and
      presence of comorbid diseases was associated with worse vision-specific QoL,
      depressive symptoms and concern about cancer recurring (all p values<0.05).
      Patients who experienced at least one stressful life event in the past year (vs
      no events) reported more depressive symptoms (p<0.01). Report of more unmet
      cancer needs was associated with worse vision-specific QoL, depressive symptoms
      and more concern about recurrence (all p values<0.05), uniquely explaining 4%-12%
      of the variance. CONCLUSIONS: For choroidal melanoma patients, an average of 2
      years after treatment, the number of physical comorbidities and unmet cancer
      needs were the strongest correlates of poorer QoL.

PMID- 24037610
TI  - Does restoration of binocular vision make any difference in the quality of life
      in adult strabismus.
AB  - BACKGROUND: To report the effect of restoration of binocular functions in adult
      strabismus on the health-related quality of life (HRQOL). METHODS: 61 adults
      undergoing strabismus surgery completed Adult Strabismus-20 (AS-20) and Amblyopia
      and Strabismus (A&SQ) HRQOL questionnaires preoperatively and postoperatively.
      Patients were grouped according to their responses to binocular tests as
      binocular vision positive (BVP) and binocular vision negative (BVN) groups.
      Changes in AS-20 and A&SQ scores of the overall group and the subgroups were
      evaluated. RESULTS: Motor success was 90%, and 43% of the cohort showed
      measurable level stereopsis and central fusion on the Worth four-dot test or on
      the synoptophore. HRQOL scores (composite, psychosocial and functional) of the
      cohort measured by AS-20 and A&SQ showed significant improvement after surgery
      (AS-20: 42,40,45 vs 85,86,84, AS&Q: 46,52,38 vs 76,75,78, p<0.05 for all
      comparisons). But the BVP (n-26) group was not found superior to the BVN (n-35)
      group both functionally and psychosocially (p>0.05). Only after the exclusion of
      the amblyopic patients, functional superiority of the BVP group (n-20) over the
      BVN group (n-20) was disclosed (AS-20: 45 vs 31, A&SQ: 28 vs 16, p<0.05), while
      the composite and psychosocial subscale score improvements were not different (AS
      20: 44,40 vs 34,38, A&SQ: 30,38 vs 20,37, p>0.05 for all comparisons).
      CONCLUSIONS: The restoration of binocular vision is possible in adults with a
      long-term history of strabismus and both AS-20 and A&SQ questionnaires are
      sensitive to detect additive effect of binocular vision on functional aspects of
      the quality of life. To increase this sensitivity, questionnaires can be modified
      to include items inquiring tasks that require fine stereopsis.

PMID- 24037611
TI  - Visual outcomes following intraophthalmic artery melphalan for patients with
      refractory retinoblastoma and age appropriate vision.
AB  - BACKGROUND/AIMS: To determine the frequency and cause of visual loss following
      intra-arterial melphalan (IAM) in patients with retinoblastoma with age
      appropriate vision. METHODS: Assessment of patients with refractory
      retinoblastoma that had undergone systemic chemotherapy, with or without local
      treatment, and were subsequently treated with IAM. Eyes of patients with a
      healthy foveola were assessed. The main outcome measures included visual, macular
      (including Pattern Visual Evoked Potentials and Fundus Fluorescein Angiography)
      and retinal functions (Electroretinograms). RESULTS: Five of twelve eyes (42%)
      demonstrated severe visual loss following IAM at last follow-up (median 21
      months). This was due to either retinal detachment (1 eye, 20%) or choroidal
      ischaemia involving the foveola (4 eyes, 80%). All 3 eyes that had technical
      difficulties or vasospasm during catheterisation suffered visual loss. 8 out of
      10 eyes that had a non-age adjusted dose of melphalan suffered visual loss.
      Electroretinograms post-IAM deteriorated in 4 of 8 eyes (50%) and Pattern Visual
      Evoked Potentials deteriorated in 3 (37%), though only one of these 3 showed
      concomitant visual acuity loss. CONCLUSIONS: Structural and vascular damage to
      the foveola limited visual acuity. Complications associated with catheterisation
      and high doses of melphalan may be contributory factors to visual morbidity.
      Although visual loss is described, no patient developed metastases and most
      retained good vision.

PMID- 24037612
TI  - Two virus-like particles that cause lytic infections in freshwater cyanobacteria.

PMID- 24037613
TI  - Application of functionalized magnetic nanoparticles in sample preparation.
AB  - Functionalized magnetic nanoparticles have attracted much attention in sample
      preparation because of their excellent performance compared with traditional
      sample-preparation sorbents. In this review, we describe the application of
      magnetic nanoparticles functionalized with silica, octadecylsilane, carbon-based
      material, surfactants, and polymers as adsorbents for separation and
      preconcentration of analytes from a variety of matrices. Magnetic solid-phase
      extraction (MSPE) techniques, mainly reported in the last five years, are
      presented and discussed. 

PMID- 24037614
TI  - Lactate biosensors: current status and outlook.
AB  - Many research efforts over the last few decades have been devoted to sensing
      lactate as an important analytical target in clinical care, sport medicine, and
      food processing. Therefore, research in designing lactate sensors is no longer in
      its infancy and now is more directed toward viable sensors for direct
      applications. In this review, we provide an overview of the most immediate and
      relevant developments toward this end, and we discuss and assess common
      transduction approaches. Further, we critically describe the pros and cons of
      current commercial lactate sensors and envision how future sensing design may
      benefit from emerging new technologies. 

PMID- 24037615
TI  - Determination of nitration degrees for the birch pollen allergen Bet v 1.
AB  - Nitration of tyrosine residues in the major birch pollen allergen Bet v 1 may
      alter the allergenic potential of the protein. The kinetics and mechanism of the
      nitration reaction, however, have not yet been well characterized. To facilitate
      further investigations, an efficient method to quantify the nitration degree (ND)
      of small samples of Bet v 1 is required. Here, we present a suitable method of
      high-performance liquid chromatography coupled to a diode array detector (HPLC
      DAD) that can be photometrically calibrated using the amino acids tyrosine (Tyr)
      and nitrotyrosine (NTyr) without the need for nitrated protein standards. The new
      method is efficient and in agreement with alternative methods based on hydrolysis
      and amino acid analysis of tetranitromethane (TNM)-nitrated Bet v 1 standards as
      well as samples from nitration experiments with peroxynitrite. The results
      confirm the applicability of the new method for the investigation of the reaction
      kinetics and mechanism of protein nitration. 

PMID- 24037616
TI  - Non-destructive elemental analysis of large meteorite samples by prompt gamma-ray
      neutron activation analysis with the internal mono-standard method.
AB  - Prompt gamma-ray neutron activation analysis (PGNAA) using the internal mono
      standard method was tested for its applicability to analyzing large solid samples
      including irregularly shaped meteorite samples. For evaluating the accuracy and
      precision of the method, large quantities of the Geological Survey of Japan
      standardized rock powders (JB-1a, JG-1a, and JP-1) were analyzed and 12 elements
      (B, Na, Mg, Al, Cl, K, Ca, Ti, Mn, Fe, Sm, and Gd) were determined by using Si as
      an internal standard element. Analytical results were mostly in agreement with
      literature values within 10 %. The precision of the method was also shown to be
      within 10 % (1sigma) for most of these elements. The analytical procedure was
      then applied to four stony meteorites (Allende, Kimble County, Leedey, Lake
      Labyrinth) and four iron meteorites (Canyon Diablo, Toluca (Mexico), Toluca
      (Xiquipilco), Squaw Creek) consisting of large chunks or single slabs. For stony
      meteorites, major elements (Mg, Al, Si, S, Ca, and Ni), minor elements (Na and
      Mn) and trace element (B, Cl, K, Ti, Co, and Sm) were determined with adequate
      accuracy. For iron meteorites, results for the Co and Ni mass fractions
      determined are all consistent with corresponding literature values. After the
      analysis, it was confirmed that the residual radioactivity remaining in the
      sample after PGNAA was very low and decreased down to the background level. This
      study shows that PGNAA with the internal mono-standard method is highly practical
      for determining the elemental composition of large, irregularly shaped solid
      samples including meteorites.

PMID- 24037617
TI  - New approach in RNA quantification using arginine-affinity chromatography:
      potential application in eukaryotic and chemically synthesized RNA.
AB  - The knowledge of RNA's role in biological systems and the recent recognition of
      its potential use as a reliable biotherapeutic tool increase the demand for
      development and validation of analytical methods for accurate analysis of RNA.
      Affinity chromatography is a unique technique because of the versatility of
      applications reliant on the affinity ligand used. Recently, an arginine-based
      matrix has been effectively applied in the purification of RNA because of the
      specific recognition mechanism for RNA molecules. This interaction is suggested
      to be due to the length of arginine side chain and its ability to produce good
      hydrogen bonding geometries, which promote multi-contact with RNA backbone or RNA
      bases, based on RNA folding. Thus, this work presents the development and
      validation of an analytical method with ultraviolet detection for the
      quantification of RNA using affinity chromatography with arginine amino acid as
      immobilized ligand. The method was validated according to International and
      European legislation for bioanalytical methods. The results revealed that the
      proposed method is suitable for the reliable detection, separation, and
      quantification of RNA, showing that the method is precise and accurate for
      concentrations up to 200 ng/MUL of RNA. Furthermore, the versatility of the
      methodology was demonstrated by its applicability in the quantification of RNA
      from different eukaryotic cells and in crude samples of chemically synthesized
      RNA. Therefore, the proposed method demonstrates a potential multipurpose
      applicability in molecular biology RNA-based analysis and RNA therapeutics. 

PMID- 24037618
TI  - The deviation of the mechanical leg axis correlates with an increased hip alpha
      angle and could be a predictor of femoroacetabular impingement.
AB  - PURPOSE: This study was designed to evaluate whether the mechanical axis
      deviation (MAD) of the leg correlates with an increased hip alpha angle as
      described by Notzli, which is associated with femoroacetabular impingement (FAI).
      METHODS: In a retrospective analysis, standing full-length anteroposterior
      radiographs were analysed in patients who suffered from symptomatic leg
      alignment. The study included 85 radiographs of 80 patients with an average age
      of 43.11 years (range 18-60 years). Five patients underwent a bilateral long-leg
      X-ray examination. All radiographs were transferred as Digital Imaging and
      Communications in Medicine data files from the Picture Archiving and
      Communications System into the OrthoPlanner software version 2.3.2. The
      radiographs were measured by one orthopaedic surgeon and one independent
      radiologist. RESULTS: The mean value of the alpha angle of Notzli was 61.43
      degrees  (49.07-74.04 degrees ). A total of 57 (67%) radiographs showed a varus
      deviation, 25 (29.5%) had a valgus malalignment and three (3.5%) a straight leg
      axis. Of 82 radiographs, 40 (48.8%) had a moderate axis deviation with a MAD <15
      or > - 15 mm and a mean alpha angle of 57.81 degrees , and 42 (51.2%) with
      extended axis deviation of a MAD > 15 or < - 15 mm had a mean alpha angle of
      62.93 degrees ; 40 (95.2%) of these 42 showed an alpha angle > 55 degrees . The
      alpha angle was significantly increased in extended axis deviation compared to
      moderate axis deviation (P = 0.001). CONCLUSIONS: This study confirmed that
      increased alpha angles were found significantly at higher degrees of axis
      deviation on the full-length radiograph. In cases of a MAD >15 or < - 15 mm and
      symptomatic coxalgia, diagnostic tests must be pursued for FAI.

PMID- 24037620
TI  - Cure models for the analysis of time-to-event data in cancer studies.
AB  - In settings when it is biologically plausible that some patients are cured after
      definitive treatment, cure models present an alternative to conventional survival
      analysis. Cure models can inform on the group of patients cured, by estimating
      the probability of cure, and identifying factors that influence it; while
      simultaneously focusing on time to recurrence and associated factors for the
      remaining patients.

PMID- 24037619
TI  - Contributions of intestine and plasma to the presystemic bioconversion of
      vicagrel, an acetate of clopidogrel.
AB  - PURPOSE: To investigate the contributions of intestine and plasma to the
      presystemic bioconversion of vicagrel, and track its subsequent bioconversion to
      2-oxo-clopidogrel in vivo and in vitro to rationalize the design of vicagrel, an
      acetate analogue of clopidogrel. METHODS: The concentration-time profiles of 2
      oxo-clopidogrel and active metabolite (AM) in presystem and circulation system
      was determined in the cannulated rats. Also, the rat intestinal S9 and human
      intestinal microsomes were conducted to examine the formation of 2-oxo
      clopidogrel and AM. Meanwhile, the esterases in plasma and intestinal fractions
      responsible for the bioconversion of vicagrel to 2-oxo-clopidogrel were screened
      by the esterase inhibition and recombinant esterases. RESULTS: The intestine was
      responsible for the formation of 2-oxo-clopidogrel and AM in vivo and in vitro,
      where carboxylesterases 2 (CE2) contributed greatly to the vicagrel cleavage
      during absorption. Other related esterases in plasma were paraoxonases (PON),
      carboxylesterases 1 (CE1) and butyrylcholine esterases (BChE). CONCLUSION: The
      findings rationalized the prodrug design hypothesis that vicagrel could overcome
      the extensive invalid hydrolysis of clopidogrel by the hepatic CE1 but experience
      the extensive hydrolysis to 2-oxo-clopidogrel and subsequent oxidation to AM in
      the intestine. This also supported the theory of improved pharmacological
      activity through facilitated formation of 2-oxo-clopidogrel, thus warranting much
      needed future clinical pharmacokinetic studies of vicagrel.

PMID- 24037622
TI  - Acute cardiovascular care IV.

PMID- 24037623
TI  - Current challenges in pulmonary hypertension.

PMID- 24037621
TI  - Common and specific cognitive deficits in schizophrenia: relationships to
      function.
AB  - The goals of the present study were to assess the interrelationships among tasks
      from the MATRICS and CNTRACS batteries, to determine the degree to which tasks
      from each battery capture unique variance in cognitive dysfunction in
      schizophrenia, and to determine the ability of tasks from each battery to predict
      functional outcome. Subjects were 104 schizophrenia patients and 132 healthy
      control subjects recruited as part of the CNTRACS initiative. All subjects
      completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief
      Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal
      Learning Test. Functional outcome was also assessed in the schizophrenia
      subjects. In both the patient and control groups, we found significant
      intercorrelations between all higher order cognitive tasks (episodic memory, goal
      maintenance, processing speed, verbal learning) but minimal relationships with
      the visual task. For almost all tasks, scores were significantly related to
      measures of functional outcome, with higher associations between CNTRACS tasks
      and performance-based measures of function and between one of the MATRICS tasks
      and self-reported functioning, relative to the other functioning measures. After
      regressing out variance shared by other tasks, we continued to observe group
      differences in performance among task residuals, particularly for measures of
      episodic memory from both batteries, although these residuals did not correlate
      as robustly with functional outcome as raw test scores. These findings suggest
      that there exists both shared and specific variance across cognitive tasks
      related to cognitive and functional impairments in schizophrenia and that
      measures derived from cognitive neuroscience can predict functional capacity and
      status in schizophrenia. 

PMID- 24037624
TI  - Pathology and pathobiology of pulmonary hypertension.
AB  - Pulmonary hypertension is a devastating, life-threatening disorder with no
      curative options, characterized by elevated pulmonary vascular resistance and
      secondary right ventricular failure. Although the etiologies of pulmonary
      arterial hypertension are multiple and its pathogenesis is complex, there is
      growing evidence that inflammation, endothelial dysfunction, aberrant vascular
      wall cell proliferation, as well as mutations in the bone morphogenetic protein
      receptor type 2 gene play a crucial role in triggering pathological vascular
      remodeling. The present article outlines the current understanding of this
      disease from the point of view of pathology and pathobiology. 

PMID- 24037625
TI  - Idiopathic pulmonary arterial hypertension.
AB  - Idiopathic pulmonary arterial hypertension (IPAH), formerly called primary
      pulmonary hypertension, is a rare disease (incidence and prevalence rates of
      approximately one and six cases per million inhabitants, respectively) with
      different clinical phenotypes. A group of diverse conditions manifest pulmonary
      arterial hypertension (PAH) and share similar pathological and/or clinical
      findings with IPAH. By definition, IPAH is diagnosed only after alternative
      diagnoses have been ruled out. Extensive investigation is needed to determine if
      PAH is associated with thyroid diseases, infectious diseases, autoimmune
      conditions, exposure to certain drugs (particularly anorexigens), certain genetic
      mutations, and so on. The presence of genetic abnormalities and risk factors
      (such as specific drug exposures) reinforces the "multiple hit" concept for the
      development of pulmonary hypertension. Fortunately, within the past two decades,
      therapeutic options have become available for IPAH, resulting in improved
      survival and clinical outcomes. At least seven different compounds have been
      registered for PAH treatment. However, even with aggressive PAH-specific therapy,
      mortality rates remain high (~40% at 5 years). Given the high mortality rates,
      the use of combinations of agents that work by different pathways has been
      advocated (either as "add-on" therapy or initial "up front" therapy). Further,
      new therapeutic agents and treatment strategies are on the near horizon, aiming
      to further improve survival from the remarkable progress already seen. 

PMID- 24037627
TI  - Pulmonary hypertension complicating connective tissue disease.
AB  - Pulmonary hypertension (PH) may complicate connective tissue disease (CTD),
      particularly systemic sclerosis (SSc, scleroderma), and markedly increases
      mortality. More than 70% of cases of PH complicating CTD occur in SSc, which is
      the major focus of this article. Pulmonary complications (i.e., interstitial lung
      disease [ILD] and PH) are the leading causes of scleroderma-related deaths.
      "Isolated" PH (i.e., without ILD) complicates SSc in 7.5 to 20% of cases;
      secondary PH may also occur in patients with SSc-associated ILD. Several clinical
      markers and specific autoantibody profiles have been associated with PH in SSc.
      The role of PH-specific therapy is controversial, as prognosis and responsiveness
      to therapy are worse in SSc-associated PH compared with idiopathic pulmonary
      arterial hypertension. We discuss medical therapies for CTD-associated PH and the
      role of lung transplantation for patients failing medical therapy. 

PMID- 24037628
TI  - Pulmonary hypertension complicating interstitial lung disease and COPD.
AB  - Pulmonary hypertension (PH) may complicate parenchymal lung disease, specifically
      interstitial lung diseases and chronic obstructive pulmonary disease, and
      uniformly increases the mortality risk. The epidemiology and degree of PH is
      variable and unique to the underlying lung disease. The clinician should exercise
      a high index of suspicion for PH complicating parenchymal lung disease especially
      given the nonspecific symptomatology and the limitations of echocardiography in
      this patient population. In general, PH-specific therapies in this setting have
      been poorly studied, with concern for increased shunting and/or
      ventilation/perfusion (V/Q) mismatch and resultant hypoxemia. A better
      understanding of the mechanisms underlying PH related to parenchymal lung disease
      may lead to novel pharmacological targets to prevent or treat this serious
      complication. 

PMID- 24037626
TI  - Heritable forms of pulmonary arterial hypertension.
AB  - Tremendous progress has been made in understanding the genetics of heritable
      pulmonary arterial hypertension (HPAH) since its description in the 1950s.
      Germline mutations in the gene coding bone morphogenetic receptor type 2 (BMPR2)
      are detectable in the majority of cases of HPAH, and in a small proportion of
      cases of idiopathic pulmonary arterial hypertension (IPAH). Recent advancements
      in gene sequencing methods have facilitated the discovery of additional genes
      with mutations among those with and without familial PAH (CAV1, KCNK3). HPAH is
      an autosomal dominant disease characterized by reduced penetrance, variable
      expressivity, and female predominance. These characteristics suggest that genetic
      and nongenetic factors modify disease expression, highlighting areas of active
      investigation. The reduced penetrance makes genetic counseling complex, as the
      majority of carriers of PAH-related mutations will never be diagnosed with the
      disease. This issue is increasingly important, as clinical testing for BMPR2 and
      other mutations is now available for the evaluation of patients and their at-risk
      kin. The possibilities to avoid mutation transmission, such as the rapidly
      advancing field of preimplantation genetic testing, highlight the need for all
      clinicians to understand the genetic features of PAH risk. 

PMID- 24037629
TI  - Is distal chronic thromboembolic pulmonary hypertension treatable with PAH
      targeted drugs?
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening
      condition that historically has a poor outcome with supportive medical treatment.
      Pulmonary endarterectomy (PEA) is the treatment of choice and offers the only
      chance of cure. A significant proportion of patients is either not suitable due
      to the distal distribution of the disease or has persistent pulmonary
      hypertension (PH) after PEA. Despite the lack of licensed therapies for CTEPH,
      the similarities in pathobiology of pulmonary arterial hypertension (PAH) and
      CTEPH has led to the compassionate use of PAH therapies in CTEPH patients. This
      article reviews the pathobiology of CTEPH and summaries the available evidence
      for the use of PAH-targeted drugs in CTEPH. 

PMID- 24037631
TI  - Inflammatory mechanisms in HIV-associated pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a severe complication of human
      immunodeficiency virus (HIV) infection and a leading major cause of death when
      present. HIV-PAH could be the consequence of multiple hits including the direct
      effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed,
      HIV infection has long been identified as an immunosuppressive disease but, since
      the advent of highly active antiretroviral treatments (HAART), HIV infection is
      considered as an inflammatory disease in which vascular complications have become
      a major cause of morbidity and death. Conversely to immunosuppression, which
      correlates with blood CD4 + T cell level, inflammation in HIV infection is due to
      the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors
      lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6
      overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only
      partially restored with HAART, usually slowly after several months or years, with
      a large heterogeneity from one patient to another. These characteristics may
      cause chronic inflammation, and we hypothesize that PAH may occur because of this
      inflammatory component despite HAART, even with apparently good response to
      therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load).
      Inflammation theory in HIV-PAH (as in other forms of PAH) could open new
      treatment options. 

PMID- 24037632
TI  - A practical approach of pulmonary hypertension in the elderly.
AB  - Recent reports from pulmonary arterial hypertension (PAH) registries suggest that
      the mean age at diagnosis is increasing, outlining a growing proportion of
      elderly male patients. As a consequence, the classical description of the disease
      is shifting and may no more be described as a rare disease typically affecting
      young women. Potential explanations of this changing picture may include an aging
      of populations in western countries, the increase in life expectancy and the
      growing awareness of PAH and emergence of potential efficient treatments.
      Diagnostic workup of severe pulmonary hypertension (PH) in the elderly should be
      performed in such a way as to discriminate between the expected consequences of
      aging, pulmonary vascular disease, and other frequent causes of secondary PH
      (left heart failure or lung disease). Careful exploration by right heart
      catheterization is mandatory, but special attention should be paid to several
      pitfalls specific to this procedure in this age group. This is a matter of
      concern as clinical trials that aim to study new specific drug therapy for PAH
      might be biased by the inclusion of misdiagnosed patients. The aim of this review
      is to highlight the main difficulties in diagnosing PAH in the elderly and to
      propose a practical approach to distinguish PAH from the other frequent causes of
      PH in this population. 

PMID- 24037633
TI  - Pulmonary hypertension associated with left heart disease.
AB  - Left heart disease (LHD) is probably the most frequent cause of pulmonary
      hypertension (PH). Although rheumatic mitral valve stenosis has been in the past
      the most common cause of this condition, PH-LHD mainly results from heart failure
      related to systolic and/or diastolic dysfunction of the left ventricle and is
      associated with elevated left-sided cardiac filling pressures. Most patients have
      passive increase in pulmonary arterial pressure because of backward transmission
      of the elevated left atrial pressure, whereas a small subset develop severe PH
      with elevated transpulmonary gradient and pulmonary vascular resistance. When
      present, PH is usually associated with a poor prognosis and increased mortality.
      Optimizing heart failure regimens and corrective valve surgery are the
      cornerstones of the treatment of PH in LHD. Although PH-LHD may evolve to right
      ventricular failure and is associated with some changes in the pulmonary vascular
      bed similar to pulmonary arterial hypertension (PAH), there is no evidence-based
      data to support the use of PAH-specific therapies in the setting of PH-LHD.
      However, recent studies suggest the usefulness of sildenafil, a phosphodiesterase
      5 inhibitor. This review addresses the epidemiology, pathophysiology, risk
      factors, and treatment controversies of PH due to LHDs. 

PMID- 24037630
TI  - Current challenges in pediatric pulmonary hypertension.
AB  - Pulmonary arterial hypertension (PAH) in the pediatric population is associated
      with a variety of underlying diseases and causes, significantly morbidity and
      mortality. In the majority of patients, PAH in children is idiopathic or
      associated with congenital heart disease (CHD), with pulmonary hypertension (PH)
      associated with connective tissue disease, a rare cause in children.
      Classification of pediatric PH has generally followed the WHO classification, but
      recognition of the importance of fetal origins of PH and developmental
      abnormalities have led to the formation of a new pediatric-specific
      classification. Incidence data from the Netherlands has revealed an annual
      incidence and point prevalence of 0.7 and 4.4 for idiopathic PAH and 2.2 and 15.6
      for associated pulmonary arterial hypertension-CHD cases per million children.
      Although the treatment with new selective pulmonary vasodilators offers
      hemodynamic and functional improvement in pediatric populations, the treatments
      in children largely depend on results from evidence-based adult studies and
      experience of clinicians treating children. A recent randomized clinical trial of
      sildenafil and its long-term extension has led to disparate recommendations in
      the United States and Europe. 

PMID- 24037634
TI  - Birth control and pregnancy management in pulmonary hypertension.
AB  - Pregnancies in patients with pulmonary arterial hypertension (PAH) are associated
      with serious complications and mortality rates of more than 50%. Advanced medical
      therapies for PAH have been developed during the past years resulting in improved
      hemodynamics, exercise capacity, quality of life, and outcome. However, despite
      these advances, pregnancy in women with PAH is still associated with excessive
      maternal mortality. Consequently, all current guidelines strongly discourage
      pregnancy and recommend an effective method of contraception in women of
      childbearing age. If this fails, early pregnancy termination is advised. Those
      patients who choose to continue pregnancy should be treated with targeted PAH
      therapies including prostacyclin analogues and/or phosphodiesterase type 5
      inhibitors. The care of the pregnant women with PAH requires a planned,
      multidisciplinary approach, preferably in a dedicated pulmonary hypertension
      referral center, focusing on close monitoring before, during and after delivery. 

PMID- 24037635
TI  - Experimental models of right heart failure: a window for translational research
      in pulmonary hypertension.
AB  - The right ventricle (RV) faces major changes in loading conditions associated
      with cardiovascular and pulmonary vascular disorders. Despite major
      pharmacological advances since the last decade, pulmonary arterial hypertension
      remains a deadly disease mainly secondary to the development of right ventricular
      failure (RVF). Several experimental models of RVF have been developed over the
      past three decades providing a particular insight in RV pathophysiology.
      Mechanisms involved in the transition from RV adaptive hypertrophy to maladaptive
      remodeling and failure in conditions of chronic RV pressure or volume overload
      are of a great interest but not yet completely understood. Further investigations
      are needed to find new therapeutic approaches for RVF. Current animal models and
      emerging concepts of translational RV research will be detailed in this review. 

PMID- 24037636
TI  - Management of severe pulmonary arterial hypertension.
AB  - Despite advances in medical therapies, pulmonary arterial hypertension (PAH),
      continues to cause significant morbidity and mortality. Although, the right
      ventricle can adapt to an increase in afterload, progression of the pulmonary
      vasculopathy that characterizes PAH causes many patients to develop progressive
      right ventricular (RV) failure. Furthermore, acute RV decompensation may develop
      from disorders that lead to either an acute increase in cardiac demand or an
      increase in ventricular afterload including interruptions in medical therapy,
      arrhythmia, or pulmonary embolism. The poor reserve of the right ventricle, RV
      ischemia, and adverse RV influence on left ventricular filling may lead to a
      global reduction in oxygen delivery and multiorgan failure. The authors present
      an approach to patients with advanced PAH focusing on both medical and surgical
      strategies to improve RV function based upon current evidence and physiological
      principles. 

PMID- 24037637
TI  - Tyrosine kinase inhibitors in pulmonary arterial hypertension: a double-edge
      sword?
AB  - New treatments for pulmonary arterial hypertension (PAH) are a crucial need. The
      increased proliferation, migration, and survival of pulmonary vascular cells
      within the pulmonary artery wall in PAH have allowed successful transposition of
      pathophysiological elements from oncologic researches. Next steps will require
      translation of these biological advances in PAH therapeutic arsenal and
      guidelines. This review synthesizes recent data concerning the role of receptor
      tyrosine kinases and their inhibitors in PAH, with implications in animal models
      and humans. Results of clinical trials are now accumulating to establish
      beneficial role of tyrosine kinase inhibitors (TKIs) in PAH and further findings
      are expected in the near future. Beside this curative approach, evidences of a
      possible TKI-induced cardiotoxicity are emerging. These safety issues raise
      concern about a potential amplified harmful effect in PAH, a pathology
      characterized by an underlying cardiac dysfunction. In addition, analyses of PAH
      registries shed light on a selective pulmonary vascular toxicity triggered by
      TKIs, especially dasatinib. These possible dual effects of the TKIs in PAH need
      to be taken in account for future pharmacological development of this therapeutic
      class in PAH. 

PMID- 24037638
TI  - Longitudinal associations between infections and atopic disorders across
      childhood and dysregulated adrenocortical functioning in early adolescence.
AB  - The present study sought to determine if exposure to common childhood medical
      problems (i.e., infections and atopic disorders [e.g., allergies, asthma]) may
      dysregulate the hypothalamic-pituitary-adrenal (HPA) axis. Longitudinal data from
      96 youth were used to examine this possibility. Medical records were drawn from
      government databases indicating the frequency of visits to healthcare facilities
      for infections and atopic disorders from infancy to early adolescence. During
      early adolescence, participants provided salivary cortisol samples from awakening
      until bedtime over 2 consecutive days. Individuals with a history of increased
      number visits for infections across childhood displayed elevated levels of
      cortisol at awakening whereas individuals with childhood histories of visits for
      atopic disorders displayed blunted diurnal cortisol slopes. These findings build
      on previous research documenting associations between infections and atopic
      disorders and cortisol by identifying longitudinal linkages from early health
      problems to later HPA axis functioning.

PMID- 24037639
TI  - Disturbed interplay between mid- and high-level vision in ASD? Evidence from a
      contour identification task with everyday objects.
AB  - Atypical visual processing in children with autism spectrum disorder (ASD) does
      not seem to reside in an isolated processing component, such as global or local
      processing. We therefore developed a paradigm that requires the interaction
      between different processes-an identification task with Gaborized object outlines
      and applied this to two age groups of 6-to-10 and 10-to-14 year old children with
      and without ASD. Event history analyses demonstrated an identification
      disadvantage in the ASD group, which remained quite stable during the temporal
      unfolding of the outline. The typically developing group particularly
      outperformed the ASD group when more complex contours were shown. Together, our
      results suggest that the interplay between local and global processes and between
      bottom-up and top-down processes is disturbed in ASD. 

PMID- 24037640
TI  - Denaturation of bovine spleen galectin-1 in guanidine hydrochloride and
      fluoroalcohols: structural characterization and implications for protein folding.
AB  - Guanidine hydrochloride (GdnHCl)-induced unfolding of bovine spleen galectin-1
      (Gal-1) exhibits three-state mechanism involving exclusive, structured tertiary
      monomer in 0.5 M GdnHCl. Gal-1 has one tryptophan residue (Trp 68) per subunit.
      Phosphorescence spectra of both Gal-1 dimer and intermediate monomer at 77 K show
      single (0,0) band at 405.6 nm, characteristics of free tryptophan environment as
      of N-acetyl-l-tryptophanamide. Unfolded Gal-1 in 4 M GdnHCl gives (0,0) band at
      longer wavelength (408.6 nm) signifying that Trp 68 is less solvent exposed,
      being localized in an environment of residual structure. Trifluoroethanol (TFE)-
      and hexafluoroisopropanol (HFIP)-induced structural changes of Gal-1 dimer and
      monomer have been investigated by far-UV CD and FTIR. CD results show reversible
      nature of beta-sheet to alpha-helix transition, with 30% helix in 80% TFE or 40%
      HFIP for Gal-1 dimer. Temperature-dependent studies show that induced helix
      entails reduced thermal stability. FTIR results reveal partial beta-sheet to
      alpha-helix conversion but with quantitative yield. At intermediate TFE
      concentration, both Gal-1 dimer and monomer aggregate as evidenced by FTIR band
      at ~1617/cm, however, the onset of aggregation and stability of aggregates for
      monomer differ from those of dimer. The results may provide important insights
      into perturbed folding problem of Gal-1. 

PMID- 24037643
TI  - Hepatoprotective effect of manganese chloride against CCl4-induced liver injury
      in rats.
AB  - The aim of the present study is to evaluate the protective effect of manganese
      chloride against carbon tetrachloride (CCl4)-induced liver injury in rats.
      Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered
      intragastrically for 28 consecutive days to male CCl4-treated rats. The
      hepatoprotective activity was assessed using various biochemical parameters such
      as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
      phosphatase (ALP), gamma-glutamyltransferase (GGT) and superoxide dismutase
      (SOD). Histopathological changes in the liver of different groups were also
      studied. Administration of CCl4 increased the serum ALT, AST, ALP and GGT but
      decreased SOD levels in rats. Treatment with manganese chloride significantly
      attenuated these changes to nearly normal levels. The animals treated with
      manganese chloride have shown decreased necrotic zones and hepatocellular
      degeneration when compared to the liver exposed to CCl4 intoxication alone. Thus,
      the histopathological studies also supported the protective effect of manganese
      chloride. Therefore, the results of this study suggest that manganese chloride
      exerts hepatoprotection via promoting antioxidative properties against CCl4
      induced oxidative liver damage.

PMID- 24037644
TI  - Production of selenium-enriched biomass by Enterococcus durans.
AB  - Selenium (Se) is an essential micronutrient for several organisms, and there is
      an increased interest about adequate sources for dietary selenium
      supplementation. The aim of this study was to evaluate the selenium
      bioaccumulation capacity of an Enterococcus strain. The isolate LAB18s was
      identified as Enterococcus durans by the VITEK(r) 2 system and analysis of both
      16S rDNA gene sequence (JX503528) and the 16S-23S rDNA intergenic spacer (ITS).
      After 24-h incubation, E. durans LAB18s bioaccumulated elevated Se(IV)
      concentrations, reaching 2.60 and 176.97 mg/g in media containing initial amounts
      of 15 and 240 mg/l sodium selenite, respectively. The isolate grew optimally and
      had high selenium bioaccumulation at initial pH of 7.0 and 30  degrees C. Time
      course studies showed that E. durans LAB18s displayed the highest bioaccumulation
      of Se(IV) after 6 h of incubation. Analyses from scanning electron microscopy
      (SEM) demonstrated the presence of filaments connecting the cells of E. durans
      LAB18s cultivated in the presence of sodium selenite. It was demonstrated that a
      considerable amount of Se(IV) was absorbed by E. durans LAB18s. Therefore, this
      strain may represent an alternative source of organic dietary selenium. 

PMID- 24037641
TI  - Sinonasal tract and nasopharyngeal adenoid cystic carcinoma: a clinicopathologic
      and immunophenotypic study of 86 cases.
AB  - Primary sinonasal tract and nasopharyngeal adenoid cystic carcinomas (STACC) are
      uncommon tumors that are frequently misclassified, resulting in inappropriate
      clinical management. Eighty-six cases of STACC included 45 females and 41 males,
      aged 12-91 years (mean 54.4 years). Patients presented most frequently with
      obstructive symptoms (n = 54), followed by epistaxis (n = 23), auditory symptoms
      (n = 12), nerve symptoms (n = 11), nasal discharge (n = 11), and/or visual
      symptoms (n = 10), present for a mean of 18.2 months. The tumors involved the
      nasal cavity alone (n = 25), nasopharynx alone (n = 13), maxillary sinus alone (n
      = 4), or a combination of the nasal cavity and paranasal sinuses (n = 44), with a
      mean size of 3.7 cm. Patients presented equally between low and high stage
      disease: stage I and II (n = 42) or stage III and IV (n = 44) disease.
      Histologically, the tumors were invasive (bone: n = 66; neural: n = 47;
      lymphovascular: n = 33), composed of a variety of growth patterns, including
      cribriform (n = 33), tubular (n = 16), and solid (n = 9), although frequently a
      combination of these patterns was seen within a single tumor. Pleomorphism was
      mild with an intermediate N:C ratio in cells containing hyperchromatic nuclei.
      Reduplicated basement membrane and glycosaminoglycan material was commonly seen.
      Necrosis (n = 16) and atypical mitotic figures (n = 11) were infrequently
      present. Pleomorphic adenoma was present in 9 cases; de-differentiation was seen
      in two patients. Immunohistochemical studies showed positive reactions for pan
      cytokeratin, CK7, CK5/6, CAM5.2, and EMA, with myoepithelial reactivity with SMA,
      p63, calponin, S100 protein and SMMHC. CD117, CEA, GFAP and p16 were variably
      present. CK20 and HR HPV were negative. STACC needs to be considered in the
      differential diagnosis of most sinonasal malignancies, particularly poorly
      differentiated carcinoma, olfactory neuroblastoma and pleomorphic adenoma.
      Surgery (n = 82), often accompanied by radiation therapy (n = 36), was generally
      employed. A majority of patients developed a recurrence (n = 52) 2-144 months
      after initial presentation. Overall mean follow-up was 19.4 years (range 0.4-37.5
      years): 46 patients died with disease (mean 6.4 years); 5 were alive with disease
      (mean 5.4 years), and 35 patients were either alive or had died of unrelated
      causes (mean 16.3 years). ACC of the SNT is uncommon. Recurrences are common. The
      following parameters, when present, suggest an increased incidence of either
      recurrence or dying with disease: mixed site of involvement, high stage disease
      (stage IV), skull base involvement, tumor recurrence, a solid histology,
      perineural invasion, bone invasion, and lymphovascular invasion.

PMID- 24037645
TI  - Apoptosis-related gene expression in glioblastoma (LN-18) and medulloblastoma
      (Daoy) cell lines.
AB  - The expression of apoptosis genes in a commercial pre-designed low-density array
      from Applied Biosystems was evaluated in two human brain cancer cell models, LN
      18 and Daoy (HTB-186TM) in comparison to the reference human primary endothelial
      cells under basic conditions. Analysis of the gene expression in the cancer cell
      lines compared to the normal control revealed features reflecting anti-apoptotic
      and inflammatory characteristics of the former. There was an overall
      downregulation of apoptosis-stimulating genes in both cancer cell lines, along
      with an upregulation of certain apoptosis inhibitors. A number of genes
      demonstrated statistically significant changes in their expressions, including
      BAX (BCL2-associated X protein); the CARD4/NLR family, CARD domain containing 4;
      CASP10 (caspase 10, apoptosis-related cysteine peptidase); DAP1 (death-associated
      protein kinase 1), and BIRC5 (baculoviral IAP repeat-containing 5). Anti
      apoptotic potential in both cell lines was demonstrated by changes in the Bax:Bcl
      2 ratio and downregulation of the APAF1 gene in LN18 cells. There was also
      significant downregulation of extrinsic signals and the TNF/FADD/inflammatory
      cascade, and upregulation of caspase inhibitors (IAPs). These results provided a
      novel molecular characterization of important human cancer cell lines, which
      might provide a useful research tool for investigating the experimental model of
      the CNS cell. 

PMID- 24037646
TI  - Treatments, complications, and healthcare utilization associated with acromegaly:
      a study in two large United States databases.
AB  - The economic burden of acromegaly in the US has been largely unknown. We describe
      the prevalence of treatment patterns, complication rates, and associated
      healthcare utilization and costs of acromegaly in the US. Patients were
      identified between 1/1/2002 and 12/31/2009 in claims databases. During 1-year
      after each continuously-enrolled patient's first acromegaly claim, pharmacy and
      medical claims were used to estimate outcomes. Regression models were used to
      adjust outcomes. There were 2,171 acromegaly patients (mean age: 45.3 years;
      49.7% female); 77.8% received the majority of their care from non
      endocrinologists. Pharmacologic treatment was used by 30.8% of patients:
      octreotide-LAR in 18.6%, dopamine agonists in 9.8%, short-acting octreotide in
      4.7%, pegvisomant in 4.1%, and lanreotide in 1.2%; 56% had biochemical
      monitoring. Comorbidities were common, ranging from 6.6% (colon neoplasms) to
      25.6% (musculoskeletal abnormalities). Mean healthcare costs were $24,900.
      Adjusted analyses indicated comorbidities increased the odds of hospitalization:
      by 76% for musculoskeletal abnormalities; 193% for cardiovascular abnormalities;
      and 56% for sleep apnea (p < 0.05). Odds of emergency department visits increased
      by 87% (musculoskeletal) and 132% (cardiovascular abnormalities) (p < 0.01).
      After adjustments, colon neoplasms were associated with $8,401 mean increase in
      costs; musculoskeletal abnormalities with $7,502, cardiovascular abnormalities
      with $13,331, sleep apnea with $10,453, and hypopituitarism with $6,742 (p <
      0.01). Complications are common and increase utilization and cost in acromegaly
      patients. Cardiovascular complications nearly tripled the odds of hospitalization
      (OR 2.93) and increased annual mean cost by $13,331. Adequate management of this
      disease may be able to reduce health care utilization and cost associated with
      these complications and with acromegaly in general.

PMID- 24037647
TI  - Surgical management of pituicytomas: case series and comprehensive literature
      review.
AB  - OBJECTIVE: Pituicytomas are rare neoplasms that typically present as solid,
      noninfiltrative tumors occupying the sella and/or suprasellar space for which
      there is no consensus on optimal surgical management. We aimed to define a
      preferred surgical strategy for these tumors based on our clinical experience and
      comprehensive review of the world literature. DESIGN: Case series and review of
      the literature. METHODS: We documented the clinical, radiographic, and surgical
      findings of three patients with pituicytoma treated at our institution, as well
      as complications and long-term outcomes. A comprehensive review of the medical
      literature identified all cases of pituicytoma for which data regarding surgical
      approach, outcome and complications could be extracted. We compared our results
      with published data. RESULTS: All three cases at our institution achieved gross
      total removal. Two patients underwent an expanded endoscopic endonasal
      transsphenoidal and transplanum (EETS-TP) approach, while one tumor was removed
      via craniotomy. Post-operatively all patients developed pan-hypopitutarism. The
      patient undergoing craniotomy suffered profound visual loss but no other
      neurological complications were noted. A literature review identified 67 reported
      cases of pituicytoma. Surgical data was available in 60 cases. Surgical approach
      was documented in 57 patients. Sixty-three surgeries were performed in which
      approach and extent of resection was available. Gross total removal was obtained
      in 33 % of craniotomies, 42 % of transsphenoidal procedures, and 100 % of
      expanded transsphenoidal procedures. Neurological complications including visual
      loss, hemiparesis and cranial nerve palsies were reported after craniotomy, but
      not after transsphenoidal approaches. Overall EETS-TP approaches were associated
      with the highest rate of gross total removal and no visual or neurological
      complications. CONCLUSIONS: EETS-TP surgery is the preferred strategy for
      surgical removal of pituicytoma. EETS-TP and transsphenoidal approaches are
      associated with higher rates of gross total removal and lower rates of
      neurological complications than craniotomy. Gross total removal should be the
      intended goal of surgery.

PMID- 24037649
TI  - Grape brandy production, composition and sensory evaluation.
AB  - Grape brandy is a spirit drink produced by wine distillation and is matured in
      wooden casks. According to legislation, it can be characterised by the
      geographical area where the grapes were produced, the grape variety used and the
      selected distillation and ageing techniques. Distillation increases ethanol
      concentration and aromatic constituents which are already present in grapes or
      are developed during fermentation and distillation. During maturation in wooden
      casks, compounds that contribute to the aroma and taste are extracted from the
      wood. Hence the spirit acquires the desired softer mouth feel, aromatic
      complexity and overall quality. Different methods of analysis are used in order
      to pursuit this process by analysing volatile and non-volatile substances and
      correlate composition with quality. Analysis can also be useful in identification
      of brandy safety, potential adulterations, provenance and differentiation from
      other spirits drinks.

PMID- 24037648
TI  - Circulating concentrations of insulin-like growth factor-I, insulin-like growth
      factor-binding protein-3, genetic polymorphisms and mammographic density in
      premenopausal Mexican women: results from the ESMaestras cohort.
AB  - The insulin-like growth factor (IGF) axis plays an essential role in the
      development of the mammary gland. High circulating levels of IGF-I and of its
      major binding protein IGFBP3 have been related with increased mammographic
      density in Caucasian premenopausal women. Some common single nucleotide
      polymorphisms (SNPs) in genes of the IGF pathway have also been suggested to play
      a role in mammographic density. We conducted a cross-sectional study nested
      within the large Mexican ESMaestras cohort to investigate the relation between
      circulating levels of IGF-I, IGFBP-3, the IGF-I/IGFBP-3 ratio, five common SNPs
      in the IGF-1, IGFBP-3 and IGF-1R genes and mammographic density in 593
      premenopausal Mexican women. Mean age at mammogram was 43.1 (standard deviation,
      SD = 3.7) years, and average body mass index (BMI) at recruitment was 28.5
      kg/m(2). Mean percent mammographic density was 36.5% (SD: 17.1), with mean dense
      tissue area of 48.3 (SD: 33.3) cm(2) . Mean IGF-I and IGFBP-3 concentrations were
      15.33 (SD: 5.52) nmol/l and 114.96 (SD: 21.34) nmol/l, respectively. No
      significant associations were seen between percent density and biomarker
      concentrations, but women with higher IGF-I and IGF-I/IGFBP-3 concentrations had
      lower absolute dense (p(trend) = 0.03 and 0.09, respectively) and nondense tissue
      areas (p(trend) < 0.001 for both parameters). However, these associations were
      null after adjustment by BMI. SNPs in specific genes were associated with
      circulating levels of growth factors, but not with mammographic density features.
      These results do not support the hypothesis of a strong association between
      circulating levels of growth hormones and mammographic density in Mexican
      premenopausal women.

PMID- 24037650
TI  - Sonographic appearance of the cavum septum pellucidum et vergae in normal fetuses
      in the second and third trimesters of pregnancy.
AB  - BACKGROUND: To characterize the cavum septum pellucidum et vergae (CSPV) in
      normal fetuses in the second to third trimester. METHODS: The cavum septum
      pellucidum (CSP) and CSPV were investigated in 322 uncomplicated singleton
      pregnancies from 25 to 39 weeks' gestation. Visualization rate, width, and
      morphology of both CSP and cavum vergae (CV) were assessed by ultrasound and MRI.
      RESULTS: The CSP and CSPV visualization rates were 100% and 7.8% (25/322),
      respectively. The mean widths were 6.3 +/- 1.2 mm (3.4-10 mm) and 6.7 +/- 1.0 mm
      (5.1-9 mm), respectively, with no significant correlation between width and
      gestational age (r = -0.108, p > 0.05 and r = -0.182, p > 0.05, respectively). In
      CSPV fetuses, the CV to CSP ratio was 1.004 +/- 0.018 (0.967-1.033). All CSPVs
      were rectangular in the transverse plane and extended posteriorly beyond the
      midpoint of the brain. CONCLUSIONS: Common features of CSPVs include (1) a
      rectangular morphology, (2) communication between the two cavities, (3) a CV
      width within the normal range for CSP, and (4) a CV-CSP ratio of 1. These
      findings may help distinguish normal from abnormal CSPV.

PMID- 24037651
TI  - Combined effect of microbial and chemical control agents on subterranean
      termites.
AB  - Termite mortality was measured when fungi were combined with bacteria or a
      chemical termiticide to determine whether a synergistic effect occurred. The
      fungus Beauveria bassiana was combined with the non-repellant chemical
      termiticide imidacloprid. Of the three B. bassiana strains tested one, B.
      bassiana ATCC 90519, was sufficiently pathogenic on its own that the advantage of
      a supplementary chemical treatment was marginal. The mortality caused by another
      fungal strain, B. bassiana ATCC 26037, was improved in combination with
      imidacloprid at both of the tested chemical concentrations over the first 14
      days. The remaining fungal strain, B. bassiana ATCC 90518, demonstrated an
      overall mortality rate in combination with imidacloprid of 82.5%, versus a rate
      of 65.0% for the fungus alone. The fungus Isaria fumosorosea (Ifr) was combined
      with the bacterium Bacillus thuringiensis (Bt). On day 5, Ifr, Bt, and the
      combined treatment at a 10(6) spores or cells/ml dosage caused 8.8%, 22.5%, and
      15.0% mortality, respectively. The Bt and combined mortality rates are not
      significantly different. Control mortality on day 5 was 5.0%. On day 13 the
      combined 10(6) treatment mortality rate was 91.3%, which was significantly higher
      than all other treatments: control at 17.5%, Ifr at 36.3% and Bt at 35.0%. When
      Ifr and Bt were applied at a 10(9) spores or cells/ml dosage, Ifr alone caused a
      mortality rate of 97.5% as early as day 5. The combination with Bt could not
      significantly increase the effectiveness of this dosage. These data demonstrate
      the potential for synergistic effects of fungal and chemical treatment methods,
      thereby broadening the use of microbial control agents and reducing the quantity
      of chemical agents necessary to effect control. 

PMID- 24037652
TI  - Live/dead state is not the factor influencing adhesion ability of Bifidobacterium
      animalis KLDS2.0603.
AB  - Two essential requirements for probiotic bifidobacteria are that they be "live"
      and have "colonization" ability, following FAO/WHO guideline recommendations. The
      amount of research on the adhesion ability of bifidobacteria compares poorly with
      that of other probiotic bacteria, such as lactobacilli. The aim of the present
      study was to determine how gastrointestinal conditions affect the adhesion
      ability of bifidobacteria, and to investigate the relationship between the
      adhesion ability and the live/dead state of bifidobacteria. The adhesion ability
      of Bifidobacterium animalis KLDS2.0603 that had been subjected to the digestive
      enzymes, pepsin, trypsin, and proteinase K, was decreased significantly, but
      these treatments did not significantly change the strain's survival rates, which
      were 98.78%, 97.60%, and 97.63% respectively. B. animalis KLDS2.0603 subjected to
      LiCl retained its adhesion ability but had a lower survival rate (59.28%) than
      the control group (P<0.01). B. animalis KLDS 2.0603 subjected to sodium
      metaperiodate exhibited higher adhesion ability than the control group (P<0.01),
      but the bacterial cells were killed totally. The results of transmission electron
      microscopy and laser scanning confocal microscopy showed that live/dead state of
      bifidobacteria was not one of the main factors that affected the adhesion ability
      of bifidobacteira, and that the substances affecting the adhesion ability of
      bifidobacteria were on the outer surface layer of the bifidobacterial cells. Our
      results also indicated that the substances related to the adhesion ability of
      bifidobacteria are proteinaceous. The above results will help us to understand
      the adhesion and colonization processes of bifidobacteria in the human
      gastrointestinal tract. 

PMID- 24037653
TI  - Devosia lucknowensis sp. nov., a bacterium isolated from hexachlorocyclohexane
      (HCH) contaminated pond soil.
AB  - Strain L15(T), a Gram-negative, motile, orange colored bacterium was isolated
      from pond soil in the surrounding area of a hexachlorocyclohexane (HCH) dump site
      at Ummari village in Lucknow, India. Phylogenetic analysis based on 16S rRNA gene
      sequence showed that strain L15(T) belongs to the family Hyphomicrobiaceae in the
      order Rhizobiales. Strain L15(T) showed highest 16S rRNA gene sequence similarity
      to Devosia chinhatensis IPL18(T) (98.0%). Chemotaxonomic data revealed that the
      major fatty acids were summed feature 8 (C18:1 omega7c and/or C18:1 omega6c),
      C18:1 omega7c 11-methyl, C16:0 and C18:0. The major polar lipids of strain L15(T)
      were diphosphatidylglycerol and phosphatidylglycerol. The genomic DNA G+C content
      of strain L15(T) was 59.8%. Polyamine profile showed the presence of sym
      homospermidine with traces of putrescine. Ubiquinone Q-10 was the major
      respiratory quinone present. Based on these data, strain L15(T) (=CCM 7977(T)
      =DSM 25398(T)) was classified as a type strain of a novel species, for which the
      name Devosia lucknowensis sp. nov. is proposed. 

PMID- 24037654
TI  - Solid state production of polygalacturonase and xylanase by Trichoderma species
      using cantaloupe and watermelon rinds.
AB  - Different solid state fermentation (SSF) sources were tested such as cantaloupe
      and watermelon rinds, orange and banana peels, for the production of
      polygalacturonase (PG) and xylanase (Xyl) by Trichoderma harzianum and
      Trichoderma virens. The maximum production of both PG and Xyl were obtained by T.
      harzianum and T. virnes grown on cantaloupe and watermelon rinds, respectively.
      Time course, moisture content, temperature, pH, supplementation with carbon and
      nitrogen sources were optimized to achieve the maximum production of both PG and
      Xyl of T. harzianum and T. virens using cantaloupe and watermelon rinds,
      respectively. The maximum production of PG and Xyl of T. harzianum and T. virens
      was recorded at 4-5 days of incubation, 50-66% moisture, temperature 28-35
      degrees C and pH 6-7. The influence of supplementary carbon and nitrogen sources
      was studied. For T. harzianum, lactose enhanced PG activity from 87 to 120
      units/g solid, where starch and maltose enhanced Xyl activity from 40 to 55-60
      units/g solid for T. virnes. Among the nitrogen sources, ammonium sulphate,
      ammonium nitrate, yeast extract and urea increased PG activity from 90 to 110-113
      units/g solid for T. harzianum. Similarly, ammonium chloride, ammonium sulphate
      and yeast extract increased Xyl activity from 45 to 55-70 units/g solid for T.
      virens. 

PMID- 24037655
TI  - Cyclooxygenase inhibitors reduce biofilm formation and yeast-hypha conversion of
      fluconazole resistant Candida albicans.
AB  - The incidence of fluconazole-resistant Candida albicans has been increasing
      worldwide. Both biofilm and fungal morphogenesis are main virulence factors of C.
      albicans cells. Extracellular fungal prostaglandins are synthesized during
      biofilm adhesion and development and through yeast-hypha conversion. Hence, we
      targeted prostaglandin synthesis with various cyclooxygenase (COX) inhibitors
      (aspirin, diclofenac, ketoprofen, tenoxicam, and ketorolac) and assessed their
      effect on fungal adhesion, biofilm formation, and yeast-hypha conversion in
      clinical isolates of Fluconazole resistant C. albicans. Significant reduction in
      fungal adhesion and detachment of mature biofilm was attained down to 1 mM
      concentrations of anti-inflammatory agents. Microscopical examination of fungal
      cells in the presence of the tested drugs showed significant reduction of germ
      tube formation. Therefore, COX inhibitors have a significant effect on reduction
      of Candida adhesion and biofilm development in correlation with fungal
      morphogenesis. Moreover, inhibition of C. albicans by COX inhibitors gave
      synergistic activity with fluconazole suggesting that combination therapeutic
      strategies may be fruitful for management of infection of Fluconazole resistant
      C. albicans. 

PMID- 24037656
TI  - Bacterial diversity and composition of an alkaline uranium mine tailings-water
      interface.
AB  - The microbial diversity and biogeochemical potential associated with a northern
      Saskatchewan uranium mine water-tailings interface was examined using culture
      dependent and -independent techniques. Morphologically-distinct colonies from
      uranium mine water-tailings and a reference lake (MC) obtained using selective
      and non-selective media were selected for 16S rRNA gene sequencing and
      identification, revealing that culturable organisms from the uranium tailings
      interface were dominated by Firmicutes and Betaproteobacteria; whereas, MC
      organisms mainly consisted of Bacteroidetes and Gammaproteobacteria. Ion Torrent
      (IT) 16S rRNA metagenomic analysis carried out on extracted DNA from tailings and
      MC interfaces demonstrated the dominance of Firmicutes in both of the systems.
      Overall, the tailings-water interface environment harbored a distinct bacterial
      community relative to the MC, reflective of the ambient conditions (i.e., total
      dissolved solids, pH, salinity, conductivity, heavy metals) dominating the
      uranium tailings system. Significant correlations among the physicochemical data
      and the major bacterial groups present in the tailings and MC were also observed.
      Presence of sulfate reducing bacteria demonstrated by culture-dependent analyses
      and the dominance of Desulfosporosinus spp. indicated by Ion Torrent analyses
      within the tailings-water interface suggests the existence of anaerobic
      microenvironments along with the potential for reductive metabolic processes. 

PMID- 24037657
TI  - Free mycolic acid accumulation in the cell wall of the mce1 operon mutant strain
      of Mycobacterium tuberculosis.
AB  - The lipid-rich cell wall of Mycobacterium tuberculosis, the agent of
      tuberculosis, serves as an effective barrier against many chemotherapeutic agents
      and toxic host cell effector molecules, and it may contribute to the mechanism of
      persistence. Mycobacterium tuberculosis strains mutated in a 13-gene operon
      called mce1, which encodes a putative ABC lipid transporter, induce aberrant
      granulomatous response in mouse lungs. Because of the postulated role of the mce1
      operon in lipid importation, we compared the cell wall lipid composition of wild
      type and mce1 operon mutant M. tuberculosis H37Rv strains. High resolution mass
      spectrometric analyses of the mce1 mutant lipid extracts showed unbound mycolic
      acids to accumulate in the cell wall. Quantitative analysis revealed a 10.7 fold
      greater amount of free mycolates in the mutant compared to that of the wild type
      strain. The free mycolates were comprised of alpha, methoxy and keto mycolates in
      the ratio 1:0.9:0.6, respectively. Since the mce1 operon is regulated in vivo,
      the free mycolates that accumulate during infection may serve as a barrier for M.
      tuberculosis against toxic products and contribute to the pathogen's persistence.

PMID- 24037658
TI  - Alternative mechanism for the evaluation of indole-3-acetic acid (IAA) production
      by Azospirillum brasilense strains and its effects on the germination and growth
      of maize seedlings.
AB  - We evaluated the production of indole-3-acetic acid (IAA) by Azospirillum
      brasilense strains in vitro (cell culture supernatants) and in vivo (stems and
      roots of maize seedlings) to clarify the role of this phytohormone as a signaling
      and effector molecule in the symbiotic interaction between maize and A.
      brasilense. The three strains all showed IAA production when cultured in NFb
      medium supplemented with 100 MUg/ml L-tryptophan. The level of IAA production was
      41.5 MUg/ml for Yu62, 12.9 MUg/ml for Az39, and 0.15 MUg/ml for ipdC-. The
      release of IAA into culture medium by the bacteria appeared to be the main
      activator of the early growth promotion observed in the inoculated maize
      seedlings. The application of supernatants with different IAA contents caused
      significant differences in the seedling growth. This observation provides the
      basis for novel technological tools for effective quality control procedures on
      inoculants. The approach described can be incorporated into different inoculation
      methods, including line sowing, downspout, and foliar techniques, and increase
      the sustainability of symbiotic plant-bacteria systems. 

PMID- 24037659
TI  - Prevalence of human papillomavirus infection and genotype distribution determined
      by the cyclic-catcher melting temperature analysis in Korean medical checkup
      population.
AB  - Although cytology screening has reduced the incidence and mortality rate of
      cervical cancer significantly, its usefulness is limited to samples from the site
      of the lesion, resulting in its low sensitivity and unsuitability for use in
      medical checkups. The purpose of the present study was to evaluate the prevalence
      of HPV infection using genotype distribution and to analyze the correlation of
      the HPV DNA test results with cytological results. We also evaluated the benefits
      of quantitative information obtained from cyclic-catcher melting temperature
      analysis (CMTA) in screening for cervical cancer. We performed cyclic-CMTA using
      AnyplexTM II HPV28 Detection in combination with cervical cytology for 2,181
      subjects. The following HPV positivity types were detected using cyclic-CMTA and
      HPV positivity was found to increase together with the severity of the cytology
      results: (1) For 419 HPV positive specimens, HPV DNA was detected in 18.1% of
      normal specimens, 78.3% of ASCUS, and all of LSIL and HSIL; (2) high-risk HPV
      DNAs were detected in 63.3% of normal (N=547), 65.9% of ASCUS (N=41), 76.9% of
      LSIL (N=13), and 88.9% of HSIL (N=9) among total detected HPV DNA regardless
      multiple detection; (3) multiple HPV genotypes were detected in 4.8% of normal
      specimens (N=2,146), 52.2% of ASCUS (N=23), 57.1% of LSIL (N=7), and 40.0% of
      HSIL (N=5). In addition, a high level of viral DNA was observed using cyclic-CMTA
      in all specimens beyond the LSIL stage according to cytology, while only 6% of
      specimens with normal cytology showed a correlation with viral quantitation by
      cyclic-CMTA. The combination of HPV genotyping with a quantitative assay and
      cytology will allow for a more accurate diagnosis of cervical cancer. 

PMID- 24037660
TI  - Analysis of the complete nucleotide sequence of a white spot syndrome virus
      isolated from Pacific white shrimp.
AB  - The fourth complete genome sequence of the white spot syndrome virus (WSSV) from
      Pacific white shrimp (Litopenaeus vannamei) isolated from Korea (WSSV-KR) was
      determined. The genome is composed of 295,884 bp encompassing 515 open reading
      frames (ORFs) among which 90 showed no sequence homology with any known protein
      in BLAST searches. The remaining 425 ORFs encode functional proteins including
      enzymes for nucleic acid metabolism, DNA replication and transcription, and
      several major structural proteins. Dot plot and linear comparisons of WSSV Korean
      strain with other WSSV isolates showed overall similarity but with some areas of
      sequence difference and one large deletion area. 

PMID- 24037661
TI  - Simultaneous detection of waterborne viruses by multiplex real-time PCR.
AB  - Norovirus, Rotavirus group A, the Hepatitis A virus, and Coxsackievirus are all
      common causes of gastroenteritis. Conventional diagnoses of these causative
      agents are based on antigen detection and electron microscopy. To improve the
      diagnostic potential for viral gastroenteritis, internally controlled multiplex
      real-time polymerase chain reaction (PCR) methods have been recently developed.
      In this study, individual real-time PCRs were developed and optimized for
      specific detections of Norovirus genogroup I, Norovirus genogroup II, Rotavirus
      group A, the Hepatitis A virus, and Coxsackievirus group B1. Subsequently,
      individual PCRs were combined with multiplex PCR reactions. In general, multiplex
      real-time PCR assays showed comparable sensitivities and specificities with
      individual assays. A retrospective clinical evaluation showed increased pathogen
      detection in 29% of samples using conventional PCR methods. Prospective clinical
      evaluations were detected in 123 of the 227 (54%) total samples used in the
      multiplex real-time PCR analysis. The Norovirus genogroup II was found most
      frequently (23%), followed by Rotavirus (20%), the Hepatitis A virus (4.5%),
      Coxsackievirus (3.5%), and Norovirus genogroup I (2.6%). Internally controlled
      multiplex real-time PCR assays for the simultaneous detection of Rotavirus,
      Coxsackievirus group B, the Hepatitis A virus, and Norovirus genogroups I and II
      showed significant improvement in the diagnosis of viral gastroenteritis. 

PMID- 24037662
TI  - Quantitative analysis of spherical microbubble cavity array formation in
      thermally cured polydimethylsiloxane for use in cell sorting applications.
AB  - Microbubbles are spherical cavities formed in thermally cured
      polydimethylsiloxane (PDMS) using the gas expansion molding technique.
      Microbubble cavity arrays are generated by casting PDMS over a silicon wafer mold
      containing arrays of deep etched pits. To be useful in various high throughput
      cell culture and sorting applications it is imperative that uniform micron-sized
      cavities can be formed over large areas (in(2)). This paper provides an in-depth
      quantitative analysis of the fabrication parameters that effect the microbubble
      cavity formation efficiency and size. These include (1) the hydrophobic coating
      of the mold, (2) the mold pit dimensions, (3) the spatial arrangement of the pit
      openings, (4) the curing temperature of PDMS pre-polymer, (5) PDMS thickness, and
      (6) the presence and composition of residual gas in the PDMS pre-polymer mixture.
      Results suggest that the principles of heterogeneous nucleation and gas diffusion
      govern microbubble cavity formation, and that surface tension prevents detachment
      of the vapor bubble that forms in the PDMS over the pit. Paramerters are defined
      that enable the fabrication of large format arrays with uniform cavity size over
      6 in(2) with a coefficient-of-variation <10 %. The architecture of the
      microbubble cavity is uniquely advantageous for cell culture. Large format arrays
      provide a highly versatile system that can be adapted for use in various high
      throughput cell sorting applications. Herein, we demonstrate the use of
      microbubble cavity arrays to dissect the cellular heterogeneity that exists in a
      tumorigenic cutaneous squamous cell carcinoma cell line at the single cell level.

PMID- 24037663
TI  - Universal hydrophilic coating of thermoplastic polymers currently used in
      microfluidics.
AB  - A number of materials used to fabricate disposable microfluidic devices are
      hydrophobic in nature with water contact angles on their surface ranging from 80
      degrees  to over 100 degrees . This characteristic makes them unsuitable for a
      number of microfluidic applications. Both the wettability and analyte adsorption
      parameters are highly dependent on the surface hydrophobicity. In this article,
      we propose a general method to coat the surface of five materials:
      polydimethylsiloxane (PDMS), cyclic olefin copolymer (COC), polyethylene
      terephthalate (PET), polycarbonate (PC), and polytetrafluoroethylene (PTFE). This
      fast and robust process, which is easily implementable in any laboratory
      including microfabrication clean room facilities, was devised by combining gas
      phase and wet chemical modification processes. Two different coatings that
      improve the surface hydrophilicity were prepared via the "dip and rinse" approach
      by immersing the plasma oxidized materials into an aqueous solution of two
      different poly(dimethylacrylamide) copolymers incorporating a silane moiety and
      functionalized with either N-acryloyloxysuccinimide (NAS) (poly(DMA-NAS-MAPS) or
      glycidyl methacrylate (GMA) (poly(DMA-GMA-MAPS). The coating formation was
      confirmed by contact angle (CA) analysis comparing the variation of CAs of
      uncoated and coated surfaces subjected to different aging treatments. The
      antifouling character of the polymer was demonstrated by fluorescence and
      interferometric detection of proteins adsorbed on the surafce. This method is of
      great interest in microfluidics due to its broad applicability to a number of
      materials with varying chemical compositions.

PMID- 24037664
TI  - Comparative secretome analysis of epithelial and mesenchymal subpopulations of
      head and neck squamous cell carcinoma identifies S100A4 as a potential
      therapeutic target.
AB  - Epithelial-mesenchymal transition (EMT) is a key contributor in tumor progression
      and metastasis. EMT produces cellular heterogeneity within head and neck squamous
      cell carcinomas (HNSCC) by creating a phenotypically distinct mesenchymal
      subpopulation that is resistant to conventional therapies. In this study, we
      systematically characterized differences in the secretomes of E-cadherin high
      epithelial-like and E-cadherin low mesenchymal-like subpopulations using unbiased
      and targeted proteomics. A total 1765 proteins showed significant changes with
      177 elevated in the epithelial subpopulation and 173 elevated in the mesenchymal
      cells. Key nodes in affected networks included NFkappaB, Akt, and ERK, and most
      implicated cellular components involved various aspects of the extracellular
      matrix. In particular, large changes were observed in multiple collagens with
      most affected collagens at much higher abundance levels in the mesenchymal
      subpopulation. These cells also exhibited a secretome profile resembling that of
      cancer-associated fibroblastic cells (CAF). S100A4, a commonly used marker for
      cancer-associated fibroblastic cells, was elevated more than 20-fold in the
      mesenchymal cells and this increase was further verified at the transcriptome
      level. S100A4 is a known mediator of EMT, leading to metastasis and EMT has been
      proposed as a potential source of cancer-associated fibroblastic cells in solid
      tumors. S100A4 knockdown by small interfering RNA led to decreased expression,
      secretion and activity of matrix metalloproteinase 2, as verified by quantitative
      PCR, multiple reaction monitoring and zymography analyses, and reduced invasion
      in collagen-embedded spheroids. Further confirmation in three-dimensional
      organotypic reconstructs showed less invasion and advanced differentiation in the
      S100A4 RNA interference samples. Orthotopic metastasis model, developed to
      validate the findings in vivo, demonstrated a decrease in spontaneous metastasis
      and augmented differentiation in the primary tumor in siS100A4 xenografts. These
      results demonstrate the value of secretome profiling to evaluate phenotypic
      conversion and identify potential novel therapeutic targets such as S100A4. 

PMID- 24037666
TI  - Longer waiting times for patients undergoing colorectal cancer surgery are not
      associated with decreased survival.
AB  - BACKGROUND AND OBJECTIVES: Wait times are a growing concern in Canada's publicly
      funded healthcare system. We sought to determine if increased wait times for
      colorectal cancer (CRC) treatments resulted in worse outcomes. METHODS: A
      population-based retrospective cohort analysis of wait times for CRC patients
      undergoing major surgical resections in Manitoba, Canada, between 2004 and 2006
      was undertaken. Administrative records were utilized to estimate total wait time
      (TWT), defined as the sum of time from index contact with the healthcare system
      to diagnosis of CRC (diagnostic wait time [DWT]) and the time from diagnosis to
      first cancer treatment (treatment wait time [TxWT]). Multivariate Cox regression
      analysis of 5-year overall survival was performed to determine the effect of TWT
      quartiles on survival. RESULTS: One thousand six hundred twenty eight patients
      with stage I-IV CRC underwent major surgery with a median TWT of 95 days.
      Predictors of lower 5-year survival included advanced age, higher stage, lower
      economic status, increased medical comorbidity, urgent presentation, living
      between 101 and 500 km from the Provincial cancer center, and not receiving
      adjuvant chemotherapy. After controlling for these variables, TWT quartiles were
      not associated with survival (P = 0.4898). CONCLUSIONS: On a population basis,
      increased TWT was not associated with worse survival, while controlling for
      important confounders.

PMID- 24037665
TI  - The coming of age of phosphoproteomics--from large data sets to inference of
      protein functions.
AB  - Protein phosphorylation is one of the most common post-translational
      modifications used in signal transduction to control cell growth, proliferation,
      and survival in response to both intracellular and extracellular stimuli. This
      modification is finely coordinated by a network of kinases and phosphatases that
      recognize unique sequence motifs and/or mediate their functions through scaffold
      and adaptor proteins. Detailed information on the nature of kinase substrates and
      site-specific phosphoregulation is required in order for one to better understand
      their pathophysiological roles. Recent advances in affinity chromatography and
      mass spectrometry (MS) sensitivity have enabled the large-scale identification
      and profiling of protein phosphorylation, but appropriate follow-up experiments
      are required in order to ascertain the functional significance of identified
      phosphorylation sites. In this review, we present meaningful technical details
      for MS-based phosphoproteomic analyses and describe important considerations for
      the selection of model systems and the functional characterization of identified
      phosphorylation sites. 

PMID- 24037667
TI  - Pathophysiology of immune-mediated demyelinating neuropathies--Part II:
      Neurology.
AB  - In the second part of this review we deal with the clinical aspects of immune
      mediated demyelinating neuropathies. We describe the relationship between
      pathophysiology and symptoms and discuss the pathophysiology of specific disease
      entities, including Guillain-Barre syndrome, chronic inflammatory demyelinating
      polyneuropathy, multifocal motor neuropathy, anti-myelin-associated glycoprotein
      neuropathy, and POEMS syndrome.

PMID- 24037668
TI  - Study changes how physicians treat metastatic prostate cancer: intermittent
      hormone therapy not as effective as continuous hormone therapy, authors say.

PMID- 24037669
TI  - Highlights from the ASCO annual meeting.

PMID- 24037670
TI  - Excellent reliability for MRI grading and prognostic parameters in acute
      hamstring injuries.
AB  - BACKGROUND: Categorical grading and other measurable MRI parameters are
      frequently utilised for predicting the outcome of hamstring injuries. However,
      the reliability and smallest detectable difference (SDD) have not been previously
      evaluated. It therefore remains unclear if the variability in previously reported
      results reflects reporting variation or actual injury status. METHODS: 25
      hamstring injuries were scored by two experienced radiologists using the Peetrons
      grading and specific prognostic MRI parameters: distance from ischial tuberosity
      (cm), extent (cranio to caudal, anterior to posterior, medial to lateral; (cm)),
      maximum cross-sectional area (%), volume (cm(3)) of the oedema. The interobserver
      and intraobserver reliability was calculated along with the SDDs for each scale
      variable. RESULTS: There were 3 Grade 0 (12%), 11 grade 1 (44%), 9 grade 2 (36%)
      and 2 grade 3 (8%) injuries. Cronbach's alpha values for grading were 1.00
      (inter) and 0.96 (intra), respectively. The intraclass correlation coefficients
      for the prognostic MRI parameters were between 0.77 and 1.0. The SDDs varied
      between each parameter. CONCLUSIONS: Excellent interobserver and intraobserver
      reliability was found for grading and prognostic MRI parameters in acute
      hamstring injuries. In daily practice and research, we can be confident that
      scoring hamstring injuries by experienced radiologists is reproducible. The
      documented SDDs allow meaningful clinical inferences to be made when assessing
      observed and reported changes in MRI status.

PMID- 24037671
TI  - Physical activity during pregnancy and the risk of gestational diabetes mellitus:
      a systematic review and meta-analysis of randomised controlled trials.
AB  - OBJECTIVES: We performed a systematic review and meta-analysis to assess the
      effects of physical activity in preventing gestational diabetes mellitus (GDM).
      SEARCH STRATEGY: We searched the literature in six electronic databases and
      bibliographies of relevant articles. SELECTION CRITERIA: We included randomised
      controlled trials on pregnant women who did not have GDM and other complications
      previously and had increased physical activity as the only intervention. The risk
      of developing GDM was documented separately for the intervention and control
      groups. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed
      quality independently. Data from the included trials were combined using a fixed
      effects model. The effect size was expressed as relative risk (RR) and 95% CI.
      MAIN RESULTS: Of the 1110 studies identified, six randomised controlled trials
      met the inclusion criteria. In three trials, the incidence of GDM was lower in
      the intervention group than in the control group, whereas two trials showed a
      higher incidence of GDM in the intervention group and the remaining trial found
      no GDM in either the intervention or control group. The meta-analysis resulted in
      a relative risk (RR) of GDM of 0.91 (95% CI 0.57 to 1.44), suggesting no
      significant difference in the risk of developing GDM between the intervention and
      the control groups. No indication of publication bias was found. CONCLUSIONS:
      Evidence was insufficient to suggest that physical activity during pregnancy
      might be effective to lower the risk of developing GDM.

PMID- 24037672
TI  - Depression and anxiety in the practice of cardiology.

PMID- 24037675
TI  - RCAI International Summer Program 2013.

PMID- 24037673
TI  - Distribution and functional expression of Kv4 family alpha subunits and
      associated KChIP beta subunits in the bed nucleus of the stria terminalis.
AB  - Regulation of BNSTALG neuronal firing activity is tightly regulated by the
      opposing actions of the fast outward potassium current, IA , mediated by alpha
      subunits of the Kv4 family of ion channels, and the transient inward calcium
      current, IT . Together, these channels play a critical role in regulating the
      latency to action potential onset, duration, and frequency, as well as dendritic
      back-propagation and synaptic plasticity. Previously we have shown that Type I
      III BNSTALG neurons express mRNA transcripts for each of the Kv4 alpha subunits.
      However, the biophysical properties of native IA channels are critically
      dependent on the formation of macromolecular complexes of Kv4 channels with a
      family of chaperone proteins, the potassium channel-interacting proteins (KChIP1
      4). Here we used a multidisciplinary approach to investigate the expression and
      function of Kv4 channels and KChIPs in neurons of the rat BNSTALG . Using
      immunofluorescence we demonstrated the pattern of localization of Kv4.2, Kv4.3,
      and KChIP1-4 proteins in the BNSTALG . Moreover, our single-cell reverse
      transcription polymerase chain reaction (scRT-PCR) studies revealed that mRNA
      transcripts for Kv4.2, Kv4.3, and all four KChIPs were differentially expressed
      in Type I-III BNSTALG neurons. Furthermore, immunoelectron microscopy revealed
      that Kv4.2 and Kv4.3 channels were primarily localized to the dendrites and
      spines of BNSTALG neurons, and are thus ideally situated to modulate synaptic
      transmission. Consistent with this observation, in vitro patch clamp recordings
      showed that reducing postsynaptic IA in these neurons lowered the threshold for
      long-term potentiation (LTP) induction. These results are discussed in relation
      to potential modulation of IA channels by chronic stress.

PMID- 24037676
TI  - Caspase-11: the driving factor for noncanonical inflammasomes.
AB  - Inflammasomes are large multiprotein platforms that mediate the processing of
      caspase-1, which in turn promotes the maturation and release of IL-1beta and IL
      18 in response to microbial and danger signals. While the canonical pathway of
      inflammasome activation has been known for some time, a novel mechanism of
      noncanonical inflammasome activation mediated by caspase-11 was more recently
      identified. This pathway engages caspase-11 to trigger both caspase-1-dependent
      and -independent production of the inflammatory cytokines IL-1beta, IL-18, and IL
      1alpha, as well as to promote pyroptosis, a form of genetically programmed cell
      death that is associated with the release of such cytokines. In this review, we
      gather together studies on both the mechanisms and implications of caspase-11
      mediated noncanonical inflammasome activation, and discuss the emerging
      importance of this pathway in regulating host defense against intracellular
      bacterial pathogens. 

PMID- 24037677
TI  - c-Rel in GVHD biology: a missing link.
AB  - Graft-versus-host disease (GVHD) is a major complication associated with
      allogeneic bone marrow transplantation (BMT). Recent advances in the treatment of
      lymphoid malignancies with BMT include exploring mechanisms that can inhibit GVHD
      while maintaining graft-versus-leukemic (GVL) effects. In this issue of the
      European Journal of Immunology, Yu et al. [Eur. J. Immunol. 2013.43: 2327-2337]
      demonstrate efficient separation of GVHD and GVL by abrogating c-Rel in T cells.
      Intrinsic c-Rel deficiency in T cells resulted in complete protection against
      GVHD in both major and minor histocompatibility mismatched murine models of BMT.
      Protection against GVHD was associated with a decreased presence of Th1 and Th17
      cells with a concomitant increase in Treg-cell numbers. Interestingly, an
      intrinsic defect of c-Rel also resulted in decreased expression of the Th1
      associated chemokine receptor CXCR3. Finally, the absence of c-Rel maintained GVL
      effects with significant tumor clearance in murine recipients. These data suggest
      that specific targeting of the T-cell-specific transcription factor c-Rel can
      inhibit GVHD while maintaining GVL effects. 

PMID- 24037682
TI  - Thermodynamics of primary photosynthesis.
AB  - The thermodynamics of photosynthesis has been much discussed, but recent articles
      have pointed to some confusion on the subject. The aim of this review is to
      clarify a limited part of this state of affairs. 

PMID- 24037683
TI  - Association of serum calcium and hypertension among adolescents aged 12-17 years
      in the rural area of Northeast China.
AB  - Calcium plays an important role in regulating body homeostasis. Several studies
      have reported the association between serum calcium and cardiovascular disease in
      adults. However, studies assessing the relationship between serum calcium and
      hypertension were limited, especially in subject populations of adolescents. The
      aim of the present study was to examine the association of serum calcium levels
      and blood pressure levels among adolescents in the rural area of Northeast China.
      A total of 2,023 students participated in this study, including 894 boys and
      1,129 girls, aged from 12 to 17 years old. We measured the body weight, height,
      systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum calcium
      concentrations of all eligible subjects, and the body mass index (BMI) was
      calculated from body weight and height. Childhood hypertension was defined as SBP
      and/or DBP >=95th percentile for age and gender. According to the results of
      multivariable linear and logistic regression analysis, we found that higher serum
      calcium levels were positively associated with childhood hypertension. In
      comparison with serum calcium levels <=2.37 mmol/L, the multivariable odds ratio
      (95 % confidence interval) of hypertension among adolescents with serum calcium
      levels >=2.53 mmol/L was 1.89 (1.41-2.53; P trend < 0.001). In addition, higher
      serum calcium levels were also positively associated with average difference in
      SBP and DBP; the average differences (95 % confidence interval) were 4.22 (2.74
      5.83; P trend < 0.001) and 2.23(1.00-3.46; P trend < 0.001), respectively. In
      conclusion, higher serum calcium concentrations were found to have an association
      with higher blood pressure levels and higher prevalence of hypertension in the
      young population. 

PMID- 24037684
TI  - Effect of combined excess iodine and low-protein diet on thyroid hormones and
      ultrastructure in Wistar rats.
AB  - The aim of the present study was to illustrate the combined effect of excess
      iodine and low-protein diet on the thyroid, and the potential molecular mechanism
      of this effect. One hundred ninety-two Wistar rats were randomly divided into the
      following groups: normal; 10- (10HI), 50- (50HI), or 100-fold excess iodine
      (100HI); low-protein; and low-protein combined with 10- (L10HI), 50- (L50HI), or
      100-fold excess iodine (L100HI). At the end of 2, 4, or 6 months, the rats were
      sacrificed for iodine concentration and thyroid hormone analyses. The
      histological appearance of the thyroid gland was observed at the end of 6 months.
      At the end of 6 months, the serum total thyroxine (TT4), free thyroxine (FT4),
      total triiodothyronine (TT3), and free triiodothyronine (FT3) levels in the
      100HI, L10HI, L50HI, and L100HI groups were significantly lower than the control
      group (P < 0.05 or P < 0.01). Serum TT4, FT4, TT3, and FT3 levels in the low
      protein excess iodine groups were significantly lower than the groups with an
      equal amount of excess iodine alone (P < 0.05 or P < 0.01). Light and electron
      microscopy showed that excess iodine caused damage to the ultrastructure of
      thyroid and apoptosis of follicular epithelial cells. In the 100HI, L50HI, and
      L100HI groups, thyroid follicular epithelial cells became flattened, and
      follicles became distended with colloid. The damage was more serious in low
      protein groups. The present findings demonstrated that the low-protein diet
      aggravated the damage to the thyroid caused by excess iodine alone. 

PMID- 24037685
TI  - Integration of 2-deoxy-2-[18F] fluoro-D-glucose PET/CT into clinical management
      of patients with Wegener's granulomatosis.
AB  - OBJECTIVE: Wegener's granulomatosis (WG) is a rare disorder characterized by
      granulomatous necrotizing vasculitis which mainly affects small- and medium-sized
      vessels. While the classical triad of involvement is upper and lower respiratory
      system and glomerulonephritis, WG may involve any organ or system in the body.
      The aim of our study was to investigate the role of positron emission
      tomography/computerized tomography (PET/CT) both in the initial evaluation and
      follow-up of patients with WG. METHODS: We retrospectively evaluated PET/CT data
      from 13 patients (6 males; 7 females) with a mean age of 45 +/- 12.4 years (range
      28-63) who underwent either initial evaluation (n = 12) or response evaluation (n
      = 2) by conventional imaging methods and FDG with PET/CT. PET/CT images were both
      visually and quantitatively evaluated. The demographic data, clinical and
      laboratory findings of each patient were also recorded from the hospital files.
      RESULTS: Lung (n = 13), parapharyngeal space (n = 8), nose (n = 8), and ear (n =
      3) were the most common disease sites detected on PET/CT. The entire initial
      evaluation patients had either solitary or multiple pulmonary nodular/mass
      lesions with marked increased FDG uptake (mean SUVmax 12 +/- 4, range 3.53-19.51)
      on PET/CT. There was no significant pathological FDG uptake in patients
      consistent with complete treatment response after appropriate immunosuppressive
      therapy. PET/CT clearly demonstrated unexpected disease sites besides the
      respiratory system, with WG involvement except kidneys. Possibly due to
      physiological urinary excretion of FDG, urine analysis, BUN and creatinine levels
      were accepted still the best way for diagnosis of renal involvement. CONCLUSION:
      FDG with PET/CT is a valuable tool in the management of patients with WG for a
      more accurate clinical evaluation regarding disease extension and treatment
      response.

PMID- 24037686
TI  - Effect of controlled lactic acid fermentation on selected bioactive and
      nutritional parameters of tempeh obtained from unhulled common bean (Phaseolus
      vulgaris) seeds.
AB  - BACKGROUND: Tempeh is a traditional Indonesian food of high nutritional quality
      obtained by fungal fermentation of dehulled, soaked and cooked legumes. The aim
      of this research was to study the effect of Lactobacillus plantarum DSM 20174
      activity on selected parameters of tempeh made from unhulled seeds of common bean
      (Phaseolus vulgaris). Lactobacillus plantarum cells were applied during soaking
      of seeds (submerged fermentation) or during solid state fermentation with
      Rhizopus microsporus var. chinensis (co-cultivation). RESULTS: Tempeh obtained
      from common beans contained 200 g kg-1 protein of 34% in vitro bioavailability.
      Fungal fermentation caused decomposition of raffinose, stachyose and verbascose
      levels in seeds, on average by 93, 84 and 73% respectively. Enhanced antiradical
      (DPPH*, ABTS*+) capacity was accompanied by increased soluble phenol content.
      Application of Lactobacillus in the fermentation procedure increased tempeh
      protein and in vitro protein bioavailability by 18 and 17% respectively. Mixed
      culture tempeh contained lower levels of stachyose (25%), verbascose (64%) and
      condensed tannins (20%). Co-cultivation enhanced both DPPH*-scavenging activity
      and antioxidant capacity. CONCLUSION: The application of Lactobacillus in most
      cases improved the nutritional parameters of tempeh from unhulled common beans.
      It may also be recommended to obtain products with diverse antioxidant properties
      as compared with fungal fermentation alone.

PMID- 24037687
TI  - Intrahepatic portal vein aneurysm--a rare entity.

PMID- 24037689
TI  - Childhood tuberculosis in Lambarene, Gabon: tuberculosis control in its infancy?
AB  - Central Africa is a region highly affected by the tuberculosis (TB) pandemic;
      however, data on local epidemiology are scarce. In the quest for gearing up
      towards tailored interventions, assessment of local baseline situations is
      mandatory. We conducted a retrospective study of 62 children registered in the TB
      register of a hospital in Lambarene, Gabon. The evaluation revealed a discrepancy
      between the TB burden and the commitment to control TB. Extrapolation of the
      incidence suggests an unexpectedly high childhood TB burden, assuming that the
      official overall TB incidence is an underestimate of the true TB burden in Gabon.

PMID- 24037692
TI  - Decreased TIP30 expression predicts poor prognosis in pancreatic cancer patients.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is known for its aggressive growth, and
      is characterized by early tissue invasion and metastasis with poor prognosis.
      Identifying prognostic markers and delineating the underlying mechanisms that
      promote progression of PDAC are important for the treatment of pancreatic cancer.
      TIP30, a newly identified tumor suppressor, appears to be involved in multiple
      processes during tumor development and metastasis. Here, we investigated the
      expression of TIP30 in PDAC and its prognostic value in PDAC patients. We
      examined the expression of TIP30 by immunohistochemistry in tissue microarrays
      containing 106 surgically resected PDAC. Kaplan-Meier analysis and Cox
      proportional hazards regression modeling analysis showed that TIP30 expression
      independently predicted better survival in pancreatectomy patients (p < 0.01).
      Moreover, decreased TIP30 expression was associated with lymph node metastasis (p
      < 0.05) and loss of E-cadherin expression (r = 0.329, p < 0.01). Suppression of
      TIP30 resulted in upregulation of Snail and subsequent downregulation of E
      cadherin in SW1990 cells containing high-level of endogenous TIP30. However, in
      the PANC-1 cells containing low level of endogenous TIP30, suppressing TIP30
      caused upregulation of Slug instead of Snail, followed by upregulation of MMP9
      rather than E-cadherin. Taken together, our work reveals that decreased TIP30
      expression is able to enhance invasion and metastasis of pancreatic cancer cells
      through upregulation of the Snail family members and may serve as an independent
      predictor for poor outcomes in PDAC patients. 

PMID- 24037694
TI  - Reducing the global burden of rabies.

PMID- 24037695
TI  - Rape as a strategy of war in the Democratic Republic of the Congo.
AB  - The Democratic Republic of the Congo (DRC) is tremendously wealthy. Abundant in
      gold, diamonds, tantalum, tin, copper, zinc and cobalt, the natural resources in
      Africa's third largest country are not equally benefiting the people. The DRC
      should sustainably be making use of their natural resources to develop the
      country, whose health, education and transport systems all suffer to this day
      from the effects of conflict. Instead, the DRC is divided with rebels, corrupt
      governments and foreign investors all fighting in one way or another for control
      over the country's wealth. The following article focuses on the emergence of rape
      as a strategy of war in the DRC. 

PMID- 24037696
TI  - International Health Links movement expands in the United Kingdom.
AB  - The need to strengthen health capacity in developing countries is widely
      documented. The World Health Organization has called for an increase in the
      number of health workers in all countries experiencing critical shortages, a
      significant scaling-up of training and more efficient use of existing health
      workers. Health Links, long-term mutually beneficial partnerships between UK
      health institutions and their counterparts in developing countries, are helping
      to fill these gaps. Links allow for the reciprocal transfer of knowledge and
      skills between partners, enabling the UK's expertise in health service delivery
      and training to be channelled towards the needs of those in developing countries,
      while also bringing a wide range of benefits to the UK. Examples of Health Links
      in Ethiopia demonstrate such benefits. An increasingly supportive policy
      environment is enabling a significant expansion in the number of Links. However,
      the quality of these Links is critical to their impact and thus there is a need
      both to continue to support those engaging in Links to develop sustainable,
      mutually beneficial strategic partnerships, and to strengthen the body of
      evidence of their impacts. 

PMID- 24037693
TI  - Screening for HIV-associated peripheral neuropathy in resource-limited settings.
AB  - INTRODUCTION: Peripheral neuropathy is the most common neurological complication
      of human immunodeficiency virus (HIV) infection but is widely under-diagnosed in
      resource-limited settings. We investigated the utility of screening tools
      administered by nonphysician healthcare workers (HCW) and quantitative sensory
      testing (QST) administered by trained individuals for identification of
      moderate/severe neuropathy. METHODS: We enrolled 240 HIV-infected outpatients
      using 2-stage cluster randomized sampling. HCWs administered the several
      screening tools. Trained study staff performed QST. Tools were validated against
      a clinical diagnosis of neuropathy. RESULTS: Participants were 65% women, mean
      age 36.4 years, median CD4 324 cells/MUL. A total of 65% were taking
      antiretrovirals, and 18% had moderate/severe neuropathy. The screening tests were
      76% sensitive in diagnosing moderate/severe neuropathy with negative predictive
      values of 84-92%. QST was less sensitive but more specific. CONCLUSIONS:
      Screening tests administered by HCW have excellent negative predictive values and
      are promising tools for scale-up in resource-limited settings. QST shows promise
      for research use.

PMID- 24037697
TI  - Environmental enteropathy: new targets for nutritional interventions.
AB  - In the developing world major public health issues such as malnutrition and
      compromised physical development are intimately linked to altered gut morphology
      and function with underlying chronic inflammatory responses. In these societies
      the downward spiral of malnutrition and infections does not seem to be remedied
      by well-informed nutritional interventions that supplement the identified
      nutrient deficiencies, suggesting that additional strategies are needed. The aim
      of this scientific opinion paper is to consider how a child from the developing
      world might benefit, separately and additively, from interventions targeted to
      impact hygiene, nutritional status, disease resistance and gut function, if
      successful interventions could be found. A failure to tackle environmental
      enteropathy (EE) may be a critical limiting factor that can explain the relative
      lack of success of interventions focussed on micronutrient supplementation so
      far. Therefore this paper starts with a summary of the aetiology and consequences
      of EE on child health and the current recommendations aimed at tackling this
      problem. Then a number of hypotheses will be considered in terms of research
      strategy to positively affect nutritional status, intestinal health and growth of
      children with EE, with the aim of inspiring future innovative strategies, for
      both the food industry and the public health sector, which could benefit millions
      of children. 

PMID- 24037688
TI  - Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a
      guideline by the German and Austrian AIDS societies (DAIG/OAG) (AWMF 055/066).
AB  - INTRODUCTION: There was a growing need for practical guidelines for the most
      common OIs in Germany and Austria under consideration of the local
      epidemiological conditions. MATERIALS AND METHODS: The German and Austrian AIDS
      societies developed these guidelines between March 2010 and November 2011. A
      structured Medline research was performed for 12 diseases, namely Immune
      reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral
      toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus
      infections, varizella zoster virus infections, progressive multifocal
      leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis
      mycobacteria infections and tuberculosis. Due to the lack of evidence by
      randomized controlled trials, part of the guidelines reflects expert opinions.
      The German version was accepted by the German and Austrian AIDS Societies and was
      previously published by the Arbeitsgemeinschaft der Wissenschaftlichen
      Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific
      Medical Societies). CONCLUSION: The review presented here is a translation of a
      short version of the German-Austrian Guidelines of opportunistic infections in
      HIV patients. These guidelines are well-accepted in a clinical setting in both
      Germany and Austria. They lead to a similar treatment of a heterogeneous group of
      patients in these countries.

PMID- 24037698
TI  - Presidential address: the role of research networks in tackling major challenges
      in international health.
AB  - One pressing challenge in the fields of international health and tropical
      medicine is how to achieve the Millennium Development Goals by 2015. Changes in
      how research is conducted are, however, contributing to progress in reaching
      these targets. Increasingly researchers from different institutions, countries
      and even continents are working together through research consortia. These
      consortia can be focused around research questions such as developing new TB
      vaccines, designed to deliver capacity building, promote advocacy, or to maintain
      efforts directed at threatened research areas such as leprosy research.
      Researchers connected through consortia can provide robust answers to research
      questions, removing duplication of effort, within a stimulating environment for
      discussion and development of research ideas. Another advantage is that south
      south research links may be strengthened, which is of increasing relevance as the
      balance of power and money is moving south, providing new opportunities for the
      African continent. However, there are disadvantages as well as advantages to
      consortia. Having too many connections can immobilise researchers in a web of
      meetings, teleconferences, and reports, reducing the time for original innovative
      ideas. Learned societies, such as the Royal Society of Tropical Medicine and
      Hygiene provide their own networks and connections and allow the bigger issues of
      international health and development to be discussed in a multidisciplinary
      environment. 

PMID- 24037699
TI  - Papua New Guinea: real progress towards MDG 4 and real challenges.
AB  - With a mortality rate in the under-5 s of 93 per 1000 live births reported in the
      1996 Demographic and Health Survey (DHS), Papua New Guinea (PNG) was at the time
      one of only four countries with stalled progress in child survival, and seemed
      destined to fail its national Millennium Development Goal (MDG) 4 target.
      However, accurate estimates have shown reductions in under-5 and infant mortality
      rates of 19% and 17% respectively, over 10 years from 1996 to 2006. In that
      period PNG adopted an integrated and coordinated approach to child health that
      includes all the essential interventions outlined in the Lancet's child survival
      series, under a framework consistent with the Western Pacific Regional Child
      Survival Strategy, associated with significant improvements in leadership and
      coordination of child health services by paediatricians at the provincial and
      national level. The reduction in child mortality since the mid-1990s is strong
      encouragement that such an approach can translate to real improvements. This
      paper outlines the recent advances in child health in PNG, identifying successful
      areas, and the challenges that lie ahead. There has been increased immunization
      coverage, introduction of vitamin A supplementation, bed-nets to prevent malaria,
      interventions to reduce mortality from acute respiratory infection, and
      improvements in the education of girls. These and improved leadership and
      coordination help to explain the recent significant gains in child survival. 

PMID- 24037700
TI  - Community-directed interventions for integrated delivery of a health package
      against major health problems in rural Uganda: perceptions on the strategy and
      its effectiveness.
AB  - Despite growing interest at national and international levels to use community
      directed interventions (CDI) for delivery of health interventions in Africa,
      inadequate information on its acceptability and effectiveness remains. This study
      aimed to examine community perceptions on CDI strategy and its effectiveness for
      integrated delivery of health interventions with different degrees of complexity
      (insecticide treated nets, vitamin A supplements to children, home management of
      malaria and direct observation treatment of tuberculosis), using community
      directed treatment with ivermectin (CDTI) as an entry point, compared to
      conventional delivery channels. The interventions were implemented in an
      incremental manner and both qualitative and quantitative methods were used at
      evaluation, three years after implementation. Coverage was significantly higher
      in CDI arm, compared to conventional delivery channels for all interventions (P <
      0.05), except for direct observation treatment of tuberculosis (P > 0.05).
      Community members expressed interest in CDI because it responds to their
      perceived health problems, actively engages them and improves access to health
      care services. CDI seemed to be appropriate for interventions that are relatively
      simple, intervention materials are available, the disease is perceived as a
      health problem affecting all sections of the community and can be easily
      integrated into their daily lives, and community structures with full community
      participation. 

PMID- 24037701
TI  - Predictors of compliance with scheduled surgery in rural Guatemala.
AB  - A non-governmental organization that helps low-income, rural, indigenous
      Guatemalans to have free or low-cost surgical care found that fewer than 60% of
      their patients kept their surgical appointments. The objective of this study was
      to identify the factors that predict compliance with scheduled surgery. All 690
      surgical candidates screened by this organization between April 2008 and March
      2009 and scheduled for surgery by August 2009 were included in this analysis. For
      the 474 adult patients the best predictors of compliance included a shorter time
      between screening and surgery, knowing someone who has had surgery, and several
      indicators of low socioeconomic status. For the 216 pediatric patients the best
      predictors of compliance included a shorter time between screening and surgery,
      having a parent who speaks Spanish in addition to the local indigenous language,
      and having a parent who knows someone who has had surgery. These findings suggest
      that the best ways to improve surgical attendance are to schedule surgery as
      close to the screening date as possible and to ensure that surgical candidates
      and their families meet a local resident who has had surgery. 

PMID- 24037702
TI  - Tobacco smoking-associated risk for tuberculosis: a case-control study.
AB  - Tobacco smoking as a risk factor for tuberculosis (TB) is often ignored. This
      study was carried out to study tobacco smoking-associated risk for tuberculosis.
      Ninety-five patients with TB, admitted in the Himalayan Institute Hospital,
      Dehradun, India and 190 controls were randomly selected and questioned regarding
      their smoking status and type, quantity and duration of tobacco used. Pulmonary
      tuberculosis (PTB) was present in 57.8%, extra-pulmonary tuberculosis (EPTB) in
      26.3% and disseminated TB in 15.7% cases. The odds ratios (ORs) for association
      of smoking tobacco (cigarette and beedi [a thin, Indian cigarette made of flaked
      tobacco wrapped in a rectangular piece of dried Diospyros melanoxylon leaf]
      collectively), cigarette and beedi with TB were 3.53 (P < 0.0001), 1.65 (P =
      0.337) and 4.49 (P < 0.0001) respectively. The ORs for PTB, EPTB and disseminated
      TB among smokers were 3.44 (P = 0.0001), 3.56 (P = 0.0067) and 2.51 (P = 0.145)
      respectively. The OR for sputum positivity for acid fast bacilli (AFB) among
      smokers was 4.65 (P = 0.0001). The ORs for a positive association with TB
      increased with duration of smoking (P < 0.0001) and number of cigarettes/beedis
      smoked (P < 0.0001). Univariate analysis showed a significant association between
      TB and other confounding risk factors viz., previous TB contact (OR 6.93, P =
      0.0001), previous TB infection (OR 38.27, P < 0.0001) and malnutrition (OR 3.77,
      P = 0.0032). In multivariate analysis using a logistic regression model, factors
      independently associated with TB were smoking (OR 3.05, P = 0.000), previous TB
      contact (OR 6.52, P = 0.001), previous TB infection (OR 37.72, P = 0.001) and
      malnutrition (OR 3.73, P = 0.009). Therefore, smoking has a strong association
      with PTB and EPTB but not with disseminated TB. Significant association exists
      between beedi smoking and TB but not between cigarette smoking and TB. The risk
      for TB depends upon dose, duration and type of tobacco smoked. 

PMID- 24037703
TI  - Knowledge, attitudes and practices survey after an outbreak of chikungunya
      infections.
AB  - In 2007, the first chikungunya outbreak ever occurring in a temperate area of the
      Northern Hemisphere was reported in Emilia-Romagna, Italy. The present study aims
      to evaluate knowledge, attitudes and practices regarding chikungunya infection.
      Information was collected by standardised telephone questionnaire, administered
      to 325 people during a seroprevalence survey performed in the outbreak area. Most
      people (61%) knew that Chikungunya virus is transmitted through mosquito bites. A
      significant proportion of respondents perceived chikungunya infection as a high
      risk disease (49.8%) and declared their intention to use mosquito repellents in
      the future (47.4%). Willingness to use skin repellents was more often declared by
      women, residents in households with children and people who knew infection
      transmission routes, while perception of high risk related to Chikungunya did not
      influence claimed future behaviour. Knowledge of the mechanisms of infection
      transmission was inversely related to risk perception: elderly people were less
      likely to know the disease than young people, but ranked the risk highest
      compared to younger age groups. Less educated residents were much more likely to
      perceive a high risk. After a chikungunya infection outbreak in a temperate area,
      where mosquito-borne infections have not been previously reported, only half of
      the study participants declared their intention to use individual protection in
      the future. Anticipated behaviour was not explained by the level of risk
      perception, but was associated with knowledge of the disease and demographic
      characteristics. 

PMID- 24037704
TI  - Erratum to "Maternal, neonatal and child health interventions and services:
      moving from knowledge of what works to systems that deliver" [International
      Health 2 (2010) 87-98].
AB  - The Publisher regrets that an error occurred in the name of the 6th listed co
      author for this paper. B. Matthias was listed in the original paper instead of M.
      Borchert; the correct listing can be seen above. 

PMID- 24037705
TI  - The cross-modal aspect of mouse visual cortex plasticity induced by monocular
      enucleation is age dependent.
AB  - Monocular enucleation (ME) drastically affects the contralateral visual cortex,
      where plasticity phenomena drive specific adaptations to compensate for the
      unilateral loss of vision. In adult mice, complete reactivation of deprived
      visual cortex involves an early visually driven recovery followed by multimodal
      plasticity 3 to 7 weeks post ME (Van Brussel et al. [2011] Cereb. Cortex 21:2133
      2146). Here, we specifically investigated the age dependence of the onset and the
      exact timing of both ME-induced reactivation processes by comparing cortical
      activity patterns of mice enucleated at postnatal day (P) 45, 90, or 120. A
      swifter open-eye potentiated reactivation characterized the binocular visual
      cortex of P45 mice. Nevertheless, even after 7 weeks, the reactivation remained
      incomplete, especially in the monocular cortex medial to V1. In comparison with
      P45, emergent cross-modal participation was demonstrated in P90 animals, although
      robust reactivation similar to enucleated adults (P120) was not achieved yet.
      Concomitantly, at 7 weeks post ME, somatosensory and auditory cortex shifted from
      a hypoactive state in P45 to hyperactivity in P120. Thus, we provide evidence for
      a presensitive period in which gradual recruitment of cross-modal recovery upon
      long-term ME coincides with the transition from adolescence to adulthood in mice.

PMID- 24037706
TI  - Vanderbilt researcher to assume leadership role with AACR: Carlos L. Arteaga, MD,
      will become organization's president in 2014.

PMID- 24037707
TI  - AACR meeting highlights new findings on drug resistance, targeted therapies.

PMID- 24037708
TI  - A high-level ab initio study of the N2 + N2 reaction channel.
AB  - A new six-dimensional (6D) global potential energy surface (PES) is proposed for
      the full range description of the interaction of the N2(1Sigmag+)+N2(1Sigmag+)
      system governing collisional processes, including N atom exchange. The related
      potential energy values were determined using high-level ab initio methods. The
      calculations were performed at a coupled-cluster with single and double and
      perturbative triple excitations level of theory in order to have a first full
      range picture of the PES. Subsequently, in order to accurately describe the
      stretching of the bonds of the two interacting N2 molecules by releasing the
      constraints of being considered as rigid rotors, for the same molecular
      geometries higher level of theory multi reference calculations were performed.
      Out of the calculated values a 6D 4-atoms global PES was produced for use in
      dynamical calculations. The ab initio calculations were made possible by the
      combined use of High Throughput Computing and High Performance Computing
      techniques within the frame of a computing grid empowered molecular simulator.

PMID- 24037709
TI  - Persistent overexpression of SERCA2a affects bladder functions under
      physiological conditions, but not in bladder outlet obstruction-induced sub-acute
      pathological conditions.
AB  - A functional impairment of the bladder and heart in a decompensated state caused
      by a pressure overload is accompanied by a decrease in the sarcoplasmic reticulum
      Ca(2+)-ATPase (SERCA2). The beneficial effects of SERCA2 overexpression in
      preserving cardiac functions have been previously reported. The aim of the
      present study was to investigate the effects of overexpressed SERCA2 on bladder
      functions under physiological and pathological conditions using partial bladder
      outlet obstruction (BOO) in SERCA2a transgenic Wistar rats (TG). Bladder
      cystometry and western blot analysis were performed using the wild-type Wistar
      rats (WT), TG, and BOO models (WTBOO and TGBOO). Persistent overexpression of
      SERCA2 induces reduced bladder compliance without hypertrophy in TG. BOO induces
      reduced bladder compliance and hypertrophy in WT and TG in the sub-acute phase,
      but persistent overexpression of SERCA2a in TG does not aggravate the bladder
      compliance and hypertrophy. In conclusion, SERCA2a overexpression affects bladder
      functions under physiological conditions, but not in BOO-induced sub-acute
      pathological conditions. 

PMID- 24037711
TI  - Polyphenolic compounds in date fruit seed (Phoenix dactylifera): characterisation
      and quantification by using UPLC-DAD-ESI-MS.
AB  - BACKGROUND: Date fruit seeds have been demonstrated to possess high antioxidant
      activities due to their high content of flavonoids and phenolic compounds. The
      objective of this work was to identify and quantify the phenolic composition of
      date seeds. METHODS: Two UPLC-DAD-ESI-MS analyses were performed on the seed of
      the Khalas variety as follows: (1) an analysis of simple phenolic compounds
      [phenolic acids, hydroxycinnamic acids, flavonols, flavones, flavan-3-ols
      (monomers, dimers and trimers)]; and (2) an analysis of all flavan-3-ols
      (monomers, and proanthocyanidin oligomers and polymers) after depolymerisation.
      RESULTS: The amount of total phenolic compounds before depolymerisation was found
      to be 2.194 +/- 0.040 g kg(-1) date seed. The analysis of flavan-3-ol monomers
      and constitutive units of proanthocyanidins after depolymerisation revealed
      50.180 +/- 1.360 g kg(-1) flavan-3-ols with 46.800 +/- 1.012 g kg(-1) epicatechin
      and 3.380 +/- 0.349 g kg(-1) catechin. CONCLUSION: The results indicate that date
      seeds are a very rich source of bioactive compounds, thus constituting strong
      candidates for functional food additives and nutraceuticals.

PMID- 24037710
TI  - Regulation of acetylation restores proteolytic function of diseased myocardium in
      mouse and human.
AB  - Proteasome complexes play essential roles in maintaining cellular protein
      homeostasis and serve fundamental roles in cardiac function under normal and
      pathological conditions. A functional detriment in proteasomal activities has
      been recognized as a major contributor to the progression of cardiovascular
      diseases. Therefore, approaches to restore proteolytic function within the
      setting of the diseased myocardium would be of great clinical significance. In
      this study, we discovered that the cardiac proteasomal activity could be
      regulated by acetylation. Histone deacetylase (HDAC) inhibitors (suberoylanilide
      hydroxamic acid and sodium valproate) enhanced the acetylation of 20S proteasome
      subunits in the myocardium and led to an elevation of proteolytic capacity. This
      regulatory paradigm was present in both healthy and acutely ischemia/reperfusion
      (I/R) injured murine hearts, and HDAC inhibition in vitro restored proteolytic
      capacities to baseline sham levels in injured hearts. This mechanism of
      regulation was also viable in failing human myocardium. With 20S proteasomal
      complexes purified from murine myocardium treated with HDAC inhibitors in vivo,
      we confirmed that acetylation of 20S subunits directly, at least in part,
      presents a molecular explanation for the improvement in function. Furthermore,
      using high-resolution LC-MS/MS, we unraveled the first cardiac 20S acetylome,
      which identified the acetylation of nine N-termini and seven internal lysine
      residues. Acetylation on four lysine residues and four N-termini on cardiac
      proteasomes were novel discoveries of this study. In addition, the acetylation of
      five lysine residues was inducible via HDAC inhibition, which correlated with the
      enhancement of 20S proteasomal activity. Taken as a whole, our investigation
      unveiled a novel mechanism of proteasomal function regulation in vivo and
      established a new strategy for the potential rescue of compromised proteolytic
      function in the failing heart using HDAC inhibitors. 

PMID- 24037712
TI  - Chloride channels in myotonia congenita assessed by velocity recovery cycles.
AB  - INTRODUCTION: Myotonia congenita (MC) is caused by congenital defects in the
      muscle chloride channel CLC-1. This study used muscle velocity recovery cycles
      (MVRCs) to investigate how membrane function is affected. METHODS: MVRCs and
      responses to repetitive stimulation were compared between 18 patients with
      genetically confirmed MC (13 recessive, 7 dominant) and 30 age-matched, normal
      controls. RESULTS: MC patients exhibited increased early supernormality, but this
      was prevented by treatment with sodium channel blockers. After multiple
      conditioning stimuli, late supernormality was enhanced in all MC patients,
      indicating delayed repolarization. These abnormalities were similar between the
      MC subtypes, but recessive patients showed a greater drop in amplitude during
      repetitive stimulation. CONCLUSIONS: MVRCs indicate that chloride conductance
      only becomes important when muscle fibers are depolarized. The differential
      responses to repetitive stimulation suggest that, in dominant MC, the affected
      chloride channels are activated by strong depolarization, consistent with a
      positive shift of the CLC-1 activation curve.

PMID- 24037713
TI  - Peripheral nerve injuries treatment: a systematic review.
AB  - Patients with peripheral nerve injuries, especially severe injury, often face
      poor nerve regeneration and incompletely functional recovery, even after surgical
      nerve repair. Current researches have extensively focused on the new approaches
      for the treatment of peripheral nerve injuries. This review summarizes treatments
      of peripheral nerve injures, from conventional suturing method, to conduit
      coaptation with stem cell and growth factor, and review the developments of
      research and clinical application of these therapies. 

PMID- 24037714
TI  - Isolation of peripheral blood mononuclear cells using glycerol density gradient.
AB  - Isolation of peripheral blood mononuclear cells (PBMCs) is fraught with
      challenges including, but not limited to, the cost of limited gradients available
      for the isolation of PBMCs. Glycerol gradient (1.077 g/ml) was used to isolate
      PBMCs from adult peripheral blood. The differentiation potential of the isolated
      cells was assessed by culturing the cells in MEM at 37  degrees C in 5 % CO2. The
      results demonstrated that the isolated cells could differentiate into committed
      linages of the erythroid progeny. LDH assay revealed that glycerol was not
      cytotoxic to the cells. The use of glycerol density as an alternative could be
      significant in cell culture experiments.

PMID- 24037715
TI  - Metabolic alterations during the growth of tumour spheroids.
AB  - Solid tumours undergo considerable alterations in their metabolism of nutrients
      in order to generate sufficient energy and biomass for sustained growth and
      proliferation. During growth, the tumour microenvironment exerts a number of
      influences (e.g. hypoxia and acidity) that affect cellular biology and the flux
      or utilisation of fuels including glucose. The tumour spheroid model was used to
      characterise the utilisation of glucose and describe alterations to the activity
      and expression of key glycolytic enzymes during the tissue growth curve. Glucose
      was avidly consumed and associated with the production of lactate and an
      acidified medium, confirming the reliance on glycolytic pathways and a diminution
      of oxidative phosphorylation. The expression levels and activities of hexokinase,
      phosphofructokinase-1, pyruvate kinase and lactate dehydrogenase in the
      glycolytic pathway were measured to assess glycolytic capacity. Similar
      measurements were made for glucose-6-phosphate dehydrogenase, the entry point and
      regulatory step of the pentose-phosphate pathway (PPP) and for cytosolic malate
      dehydrogenase, a key link to TCA cycle intermediates. The parameters for these
      key enzymes were shown to undergo considerable variation during the growth curve
      of tumour spheroids. In addition, they revealed that the dynamic alterations were
      influenced by both transcriptional and posttranslational mechanisms. 

PMID- 24037716
TI  - Epigenetic silencing of Aristaless-like homeobox-4, a potential tumor suppressor
      gene associated with lung cancer.
AB  - Using genome-wide methylation screening, we found Aristaless-like homeobox-4
      (ALX4) preferentially methylated in lung cancer. ALX4 is a putative transcription
      factor that belongs to the family of paired-class homeoproteins involved in
      epithelial development. However, the role of ALX4 in tumorigenesis remains
      largely unclear. Here, we analyzed its epigenetic regulation, biological
      functions and related molecular mechanisms in lung cancer. CpG island methylation
      and expression of ALX4 were evaluated by methylation-specific polymerase chain
      reaction (PCR), bisulfite genomic sequencing, reverse-transcription PCR and
      Western blotting. ALX4 functions were determined by cell viability, colony
      formation, flow cytometry and in vivo tumorigenicity assays. ALX4
      hypermethylation was detected in 55% (54/98) of primary lung cancers compared to
      none (0/20) of the normal lung tissue samples tested (p < 0.01). ALX4 was readily
      expressed in normal lung tissues with an unmethylated status, but downregulated
      or silenced in 90% (9/10) of lung cancer cell lines with a hypermethylation
      status. Demethylation experiments further confirmed that loss of ALX4 expression
      was regulated by CpG island hypermethylation. Re-expression of ALX4 in lung
      cancer cell lines suppressed cell viability, colony formation and migration,
      whereas it induced apoptosis and G1/S arrest and restrained the tumorigenicity in
      nude mice. These effects were associated with upregulation of proapoptotic
      proteins caspase-7, -8 and -9, and downregulation of Bcl-2. On the other hand,
      knockdown of ALX4 expression by siRNA increased cell viability and proliferation,
      whereas it inhibited apoptosis and cell cycle arrest. In conclusion, our results
      suggest that ALX4 is a novel putative tumor suppressor with epigenetic silencing
      in lung carcinogenesis. 

PMID- 24037718
TI  - Lessons learned from the 2011 debacle of the Fukushima nuclear power plant.
AB  - The history of nuclear power generation in Japan is analyzed with respect to how
      the organizational structure of the "nuclear villages," composed of government,
      private companies and the academic world, negotiated with the growing technology
      before the Fukushima accident took place. Although nuclear specialists were aware
      of the potential for a disaster, that did not prevent the enthusiasm for nuclear.
      The majority of people trusted that new technology would make life easier. The
      organizational structure of the village consisted of a triangle in which each of
      the three groups and sub-groups maintained relationships with each other and with
      the village as a whole to secure its own share of the economic benefits. Based on
      the sociological theory of norm, we demonstrate that the structure and nature of
      the relationships in the village facilitated the acceptance of nuclear power
      despite the element of threat. 

PMID- 24037717
TI  - Prevalence of bifid median nerves and persistent median arteries and their
      association with carpal tunnel syndrome in a sample of Latino poultry processors
      and other manual workers.
AB  - INTRODUCTION: The prevalence of bifid median nerves and persistent median
      arteries, their co-occurrence, and their relationship to carpal tunnel syndrome
      (CTS) are only understood partially. METHODS: We screened 1026 wrists of 513
      Latino manual laborers in North Carolina for bifid median nerves and persistent
      median arteries using electrodiagnosis and ultrasound. RESULTS: A total of 8.6%
      of wrists had a bifid median nerve, and 3.7% of wrists had a persistent median
      artery independent of subgroup ethnicity, age, gender, or type of work. An
      association with definite carpal tunnel syndrome was not found. The presence of
      either anatomic variant was associated with a high likelihood of co-occurrence of
      another variant in the same or the contralateral wrist. CONCLUSIONS: The
      occurrence of median anatomic variants can be determined in field studies using
      ultrasound. Persistent median arteries and bifid median nerves tend to co-occur
      but do not put manual laborers at additional risk of developing CTS.

PMID- 24037719
TI  - Endoscopic sonography and sonographically guided fine-needle aspiration biopsy in
      the diagnosis of unusual pancreatic metastases from synovial sarcoma.
AB  - Pancreatic metastases are commonly solitary solid lesions frequently derived from
      primary renal cell carcinoma, lung cancer, or melanoma. Very few case reports
      have described cystic-appearing metastases in the pancreas and even fewer have
      reported a combination of cystic and solid metastatic lesions. Synovial sarcoma
      is a rare and aggressive soft tissue neoplasm, frequently metastasizing to the
      lungs and bones. We present a case of primary synovial sarcoma with multiple
      solid and cystic-appearing pancreatic metastases diagnosed by endoscopic
      ultrasound and sonographically guided fine-needle aspiration.

PMID- 24037720
TI  - Characterization of the polymorphic states of copper(II)-bound Abeta(1-16)
      peptides by computational simulations.
AB  - Understanding the polymorphic states of metal amyloid beta (Abeta) interactions
      helps to elucidate metal-mediated events in the pathogenesis of Alzheimer's
      disease. Systematic investigations on the effects of metal ions such as Cu(2+)
      and Zn(2+) on the structural and thermodynamic properties of Abeta at the
      molecular lever seem desirable. In this study, a set of new AMBER force field
      parameters was developed to model various Cu(2+) coordination spheres of Abeta.
      These parameters including force constants and partial charges obtained using
      restrained electrostatic potential method were then validated in replica-exchange
      molecular dynamics simulations on six Cu(2+)-Abeta(1-16) systems. The Cu(2+)
      coordination geometry differs depending on the Cu(2+) binding fashions. The
      structural analyses reveal that Abeta(1-16) prefers turn conformations, which
      provides a geometrical favor to establish multiple Cu(2+) coordination modes in
      solution at physiological pH. The relative stability of different Cu(2+)-Abeta(1
      16) complexes was estimated by free energy calculations. The Cu(2+) ligands in
      the most stable Cu(2+)-Abeta(1-16) structure involve Glu(3) , His(6) , His(13)
      and His(14) in terms of MM/3D-RISM (molecular mechanics/three-dimensional
      reference interaction site model). The solvation free energy and conformational
      entropy calculated by 3D-RISM method suggest that the binding of Cu(2+) within
      Abeta(1-16) is a spontaneous process. The overlap of the preparation free energy
      distributions demonstrates the heterogeneous states of Abeta(1-16) conformations
      that are ready for Cu(2+) binding whereas the populations of such polymorphic
      states may shift at differing pH.

PMID- 24037721
TI  - Improving colon cancer screening in community clinics.
AB  - BACKGROUND: The authors evaluated the effectiveness and cost effectiveness of 2
      interventions designed to promote colorectal cancer (CRC) screening in safety-net
      settings. METHODS: A 3-arm, quasi-experimental evaluation was conducted among 8
      clinics in Louisiana. Screening efforts included: 1) enhanced usual care, 2)
      literacy-informed education of patients, and 3) education plus nurse support.
      Overall, 961 average-risk patients ages 50 to 85 years were eligible for routine
      CRC screening and were recruited. Outcomes included CRC screening completion and
      incremental cost effectiveness using literacy-informed education of patients and
      education plus nurse support versus enhanced usual care. RESULTS: The baseline
      screening rate was <3%. After the interventions, the screening rate was 38.6%
      with enhanced usual care, 57.1% with education, and 60.6% with education that
      included additional nurse support. After adjusting for age, race, sex, and
      literacy, patients who received education alone were not more likely to complete
      screening than those who received enhanced usual care; and those who received
      additional nurse support were 1.60-fold more likely to complete screening than
      those who received enhanced usual care (95% confidence interval, 1.06-2.42; P =
      .024). The incremental cost per additional individual screened was $1337 for
      education plus nurse support over enhanced usual care. CONCLUSIONS: Fecal occult
      blood test rates were increased beyond enhanced usual care by providing brief
      education and nurse support but not by providing education alone. More cost
      effective alternatives to nurse support need to be investigated.

PMID- 24037722
TI  - COX-2, TFF1, and Src define better prognosis in young patients with gastric
      cancer.
AB  - BACKGROUND AND OBJECTIVES: Despite its dwindling occurrence, gastric cancer
      remains a leading cause of cancer related mortality worldwide. Molecular
      determinants of prognosis that impact survival are being sought out as a means to
      facilitate rational clinical decision-making and enhance patient management. In
      this study, we evaluated three molecules implicated in gastric carcinogenesis and
      demonstrated that the differential expression of cyclooxygenase-2 (COX-2) and the
      viral oncogene homolog Src proteins could explain the differences in survival
      observed in patients older and younger than 50 years of age. METHODS: We
      evaluated 5-year survival in a cohort of 423 gastric cancer patients using
      chronological age as a variable. Additionally, we assessed the protein expression
      of three molecules (COX-2, TFF1, Src) implicated in the pathogenesis of gastric
      cancer using immunohistochemistry. RESULTS: We found that patients younger than
      50 years of age had a better 5-year survival rate in all tumor stages. We found
      that the expression of COX-2 and Src correlated significantly with survival in
      this group without any significant impact attributable to TFF1. CONCLUSIONS: Our
      study demonstrates that young gastric cancer patients have a better prognostic
      outlook that could in part be explained by the differential expression of COX-2
      and Src.

PMID- 24037723
TI  - Colistin therapy for multidrug-resistant Gram-negative infection: clinical
      outcome and risk factors.

PMID- 24037724
TI  - CMV serostatus still has an important prognostic impact in de novo acute leukemia
      patients after allogeneic stem cell transplantation: a report from the Acute
      Leukemia Working Party of EBMT.
AB  - We analyzed the prognostic impact of donor and recipient cytomegalovirus (CMV)
      serostatus in 16,628 de novo acute leukemia patients after allogeneic stem cell
      transplantation (allo-SCT). Compared with CMV-seronegative recipients who
      underwent allograft from a CMV-seronegative donor, cases of CMV seropositivity of
      the donor and/or the recipient showed a significantly decreased 2-year leukemia
      free survival (44% vs 49%, P < .001) and overall survival (50% vs 56%, P < .001),
      and increased nonrelapse mortality (23% vs 20%, P < .001). Both groups showed a
      comparable relapse incidence and 2-year probability of graft-versus-host disease.
      The negative prognostic effects of CMV seropositivity of the donor and/or the
      recipient (vs CMV seronegativity of both) were significantly stronger for acute
      lymphoblastic leukemia (ALL) than for acute myeloid leukemia (AML), resulting in
      a markedly reduced 2-year overall survival (46% vs 55% for ALL compared with 52%
      vs 56% for AML). The important prognostic impact of donor/recipient CMV
      serostatus remained in a multivariate Cox regression analysis including the other
      prognostic variables. We conclude that donor and/or recipient CMV seropositivity
      is still associated with an adverse prognosis in de novo acute leukemia patients
      after allo-SCT despite the implementation of sophisticated strategies for
      prophylaxis, monitoring, and (preemptive) treatment of CMV.

PMID- 24037725
TI  - Genome-wide copy-number analyses reveal genomic abnormalities involved in
      transformation of follicular lymphoma.
AB  - Follicular lymphoma (FL), the second most common type of non-Hodgkin lymphoma in
      the western world, is characterized by the t(14;18) translocation, which is
      present in up to 90% of cases. We studied 277 lymphoma samples (198 FL and 79
      transformed FL [tFL]) using a single-nucleotide polymorphism array to identify
      the secondary chromosomal abnormalities that drive the development of FL and its
      transformation to diffuse large B-cell lymphoma. Common recurrent chromosomal
      abnormalities in FL included gains of 2, 5, 7, 6p, 8, 12, 17q, 18, 21, and X and
      losses on 6q and 17p. We also observed many frequent small abnormalities,
      including losses of 1p36.33-p36.31, 6q23.3-q24.1, and 10q23.1-q25.1 and gains of
      2p16.1-p15, 8q24.13-q24.3, and 12q12-q13.13, and identified candidate genes that
      may be driving this selection. Recurrent abnormalities more frequent in tFL
      samples included gains of 3q27.3-q28 and chromosome 11 and losses of 9p21.3 and
      15q. Four abnormalities, gain of X or Xp and losses of 6q23.2-24.1 or 6q13-15,
      predicted overall survival. Abnormalities associated with transformation of the
      disease likely impair immune surveillance, activate the nuclear factor-kappaB
      pathway, and deregulate p53 and B-cell transcription factors. 

PMID- 24037726
TI  - Variant ALDH2 is associated with accelerated progression of bone marrow failure
      in Japanese Fanconi anemia patients.
AB  - Fanconi anemia (FA) is a severe hereditary disorder with defective DNA damage
      response and repair. It is characterized by phenotypes including progressive bone
      marrow failure (BMF), developmental abnormalities, and increased occurrence of
      leukemia and cancer. Recent studies in mice have suggested that the FA proteins
      might counteract aldehyde-induced genotoxicity in hematopoietic stem cells.
      Nearly half of the Japanese population carries a dominant-negative allele (rs671)
      of the aldehyde-catalyzing enzyme ALDH2 (acetaldehyde dehydrogenase 2), providing
      an opportunity to test this hypothesis in humans. We examined 64 Japanese FA
      patients, and found that the ALDH2 variant is associated with accelerated
      progression of BMF, while birth weight or the number of physical abnormalities
      was not affected. Moreover, malformations at some specific anatomic locations
      were observed more frequently in ALDH2-deficient patients. Our current data
      indicate that the level of ALDH2 activity impacts pathogenesis in FA, suggesting
      the possibility of a novel therapeutic approach. 

PMID- 24037727
TI  - Sex differences in serum CK activity but not in glomerular filtration rate after
      resistance exercise: is there a sex dependent renal adaptative response?
AB  - We investigated differences in sex responses in serum CK activity and renal
      function measured by glomerular filtration rate (GFR) after an exercise session.
      Twenty-two healthy and trained volunteers (11 males and 11 females) performed 17
      resistance exercises with 3 * 12 repetitions in a circuit training fashion.
      Subjects provided blood samples prior to exercise session, and at 24, 48, and 72
      h following exercise sessions for creatine kinase and creatinine. Twenty-four
      hour urine samples were collected before and 72 h after the exercise. Estimate
      (e) GFR was obtained by using the Chronic Kidney Disease Epidemiology
      Collaboration equation adjusted for males and females. After the exercise
      session, males showed greater serum CK activity than females (p < 0.02), serum
      creatinine increased 31.3 % for males and 29.8 % for females, and urinary
      creatinine decreased on average 5.4 % for males and 0.6 % for females, with no
      significant differences (p > 0.05) between sex for serum and urinary creatinine.
      eGFR decreased significantly for males (~10 %) and females (~8 %), but also
      without a difference between the sexes (p > 0.05). The correlation between CK and
      eGFR was significant for males (r = -0.794; p = 0.003), and females (r = -0.8875;
      p < 0.001). A significant negative correlation between CK activity and the eGFR
      indice of renal function in both males and females was observed. Additionally,
      the renal function compromise was similar for both sexes, despite males
      presenting greater exercise-induced skeletal muscle damage when compared to
      females. 

PMID- 24037728
TI  - Regulation of gastric motility and blood flow during acute nociceptive
      stimulation of the paraspinal muscles in urethane-anaesthetised rats.
AB  - The aim of this study was to examine gastric motility and blood flow during
      nociceptive hypertonic saline injections (HS) in paraspinal muscles of urethane
      anaesthetised rats. Gastric pressure was not affected by HS in intact or
      vagotomised conditions. After cervical spinalisation, it was decreased by
      injections at T13 or L6 but not T2. Moreover, HS injections at T13 produced
      greater gastric pressure decreases compared with L6 and T2 and increased gastric
      sympathetic nerve activity. Blood pressure and gastric blood flow were decreased
      by T13 injections in spinal cord intact but not spinalised rats. Besides,
      isotonic saline injections (non-nociceptive) produced non-significant or marginal
      effects. These results indicate that gastric motility is decreased by nociceptive
      input from paraspinal muscles in spinalised rats through activation of the
      gastric sympathetic nerve. Although gastric blood flow was also decreased by
      nociceptive stimulation at T13 in spinal cord intact rats, these changes seem to
      depend on blood pressure. 

PMID- 24037729
TI  - Cortical excitability differences in hand muscles follow a split-hand pattern in
      healthy controls.
AB  - INTRODUCTION: Differences in cortical and axonal excitability may underlie
      preferential atrophy of abductor pollicis brevis (APB) and first dorsal
      interosseous (FDI) in amyotrophic lateral sclerosis, termed the split-hand.
      Consequently, this study aimed to determine whether differences in excitability
      follow a split-hand pattern across the intrinsic hand muscles. METHODS:
      Excitability studies were undertaken using threshold tracking techniques in 26
      healthy controls with responses recorded over APB, FDI, and abductor digiti
      minimi. RESULTS: Short interval intracortical inhibition was significantly
      greater from the APB and FDI. In addition, motor evoked potential amplitude was
      greater, while cortical silent period was longer from APB and FDI. At a
      peripheral level, the strength-duration time constant was greater when recorded
      over APB. CONCLUSIONS: This study establishes that differences in cortical
      excitability follow the split-hand pattern in healthy controls, a finding
      potentially explained by evolution of specialized activity of APB/FDI in complex
      hand tasks. Muscle Nerve 49: 836-844, 2014.

PMID- 24037730
TI  - Increased oral availability and brain accumulation of the ALK inhibitor
      crizotinib by coadministration of the P-glycoprotein (ABCB1) and breast cancer
      resistance protein (ABCG2) inhibitor elacridar.
AB  - Crizotinib is an oral tyrosine kinase inhibitor approved for treating patients
      with non-small cell lung cancer (NSCLC) containing an anaplastic lymphoma kinase
      (ALK) rearrangement. We used knockout mice to study the roles of P-glycoprotein
      (ABCB1) and breast cancer resistance protein (ABCG2) in plasma pharmacokinetics
      and brain accumulation of oral crizotinib, and the feasibility of improving
      crizotinib kinetics using coadministration of the dual ABCB1/ABCG2 inhibitor
      elacridar. In vitro, crizotinib was a good transport substrate of human ABCB1,
      but not of human ABCG2 or murine Abcg2. With low-dose oral crizotinib (5 mg/kg),
      Abcb1a/1b(-/-) and Abcb1a/1b;Abcg2(-/-) mice had an approximately twofold higher
      plasma AUC than wild-type mice, and a markedly (~40-fold) higher brain
      accumulation at 24 hr. Also at 4 hr, crizotinib brain concentrations were ~25
      fold, and brain-to-plasma ratios ~14-fold higher in Abcb1a/1b(-/-) and
      Abcb1a/1b;Abcg2(-/-) mice than in wild-type mice. High-dose oral crizotinib (50
      mg/kg) resulted in comparable plasma pharmacokinetics between wild-type and
      Abcb1a/1b(-/-) mice, suggesting saturation of intestinal Abcb1. Nonetheless,
      brain accumulation at 24 hr was still ~70-fold higher in Abcb1a/1b(-/-) than in
      wild-type mice. Importantly, oral elacridar coadministration increased the plasma
      and brain concentrations and brain-to-plasma ratios of crizotinib in wild-type
      mice, equaling the levels in Abcb1a/1b;Abcg2(-/-) mice. Our results indicate that
      crizotinib oral availability and brain accumulation were primarily restricted by
      Abcb1 at a non-saturating dose, and that coadministration of elacridar with
      crizotinib could substantially increase crizotinib oral availability and delivery
      to the brain. This principle might be used to enhance therapeutic efficacy of
      crizotinib against brain metastases in NSCLC patients.

PMID- 24037731
TI  - Long-term fertilisation causes excess supply and loss of phosphorus in purple
      paddy soil.
AB  - BACKGROUND: Phosphorus (P) loss from cropland is accelerating the eutrophication
      of waters around the world such as the Three Gorges Reservoir (TGR) in China. We
      investigated whether purple paddy soil under long-term P applications was a major
      source of P efflux to the TGR. RESULTS: Substantial surplus P in the plough layer
      (0-20 cm) was evident after 15-year P applications. Available P (Olsen-P) in the
      plough layer ranged from 1.9 to 42.4 mg kg(-1) and some of which will exceed the
      threshold of 30 mg kg(-1) for environmental concern within 7 years of P
      application (inorganic NPK with or without organic fertiliser). Between 30 and
      70% of Olsen-P was leached out of the 0-30 cm soil layer. Surplus P resulted in
      high P concentrations in the surface water during the rice cropping season, and
      these concentrations exceeded those in most waters of the TGR and exceeded the
      critical level for eutrophication (0.1 mg L(-1)) during the first 10 days after
      rice planting. Furthermore, total P in run-off due to rainfall events exceeded
      the level for eutrophication, with a total loss of 43.2-147.9 g P ha(-1)
      depending on the fertilisation. CONCLUSION: Current agronomic P management in
      purple paddy soil is environmentally unsustainable in terms of the adverse impact
      on surface water quality. Integrated P management practices are urgently required
      to optimise crop yield while minimising P loss in order to protect surface water
      quality in the TGR region.

PMID- 24037732
TI  - Can self-preservation be virtuous in disaster situations?

PMID- 24037733
TI  - Apoptotic effect of methanol extract of Picrasma quassioides by regulating
      specificity protein 1 in human cervical cancer cells.
AB  - In the present study, we examined the effects of methanol extracts of Picrasma
      quassioides (MEPQ) on apoptosis in human cervical cancer cells. The results
      showed that MEPQ decreased the viability and induced caspase-dependent apoptosis
      in HEp-2 cells. MEPQ decreased specificity protein 1 (Sp1) in HEp-2 cells,
      whereas Sp1 mRNA was not changed. We found that MEPQ reduced Sp1 protein through
      proteasome-dependent protein degradation, but not the inhibition of protein
      synthesis. Also, MEPQ increased the expressions of Bad and truncated Bid (t-Bid)
      but did not alter other Bcl-2 family members. The knock-down of Sp1 by both Sp1
      interfering RNA and Mithramycin A, Sp1 specific inhibitor clearly increased Bad
      and t-Bid expression to decrease cell viability and induce apoptosis. In
      addition, MEPQ inhibited cell viability and induced apoptotic cell death through
      the modulation of Sp1 in KB cells. These results suggest that MEPQ may be a
      potential anticancer agent for human cervical cancer.

PMID- 24037734
TI  - MSMB gene variant alters the association between prostate cancer and number of
      sexual partners.
AB  - BACKGROUND: Recently, a genetic variant (rs10993994) in the MSMB gene associated
      with prostate cancer (PCa) risk was shown to correlate with reduced prostate
      secretory protein of 94 amino acids (PSP94) levels. Although the biological
      activity of PSP94 is unclear, one of its hypothesized functions is to protect
      prostatic cells from pathogens. Number of sexual partners and a history of
      sexually transmitted infections (STIs) have been positively associated with PCa
      risk, and these associations may be related to pathogen-induced chronic prostatic
      inflammation. Based on these observations, we investigated whether MSMB genotype
      modifies the PCa-sexual history association. METHODS: We estimated odds ratios
      (ORs) and 95% confidence intervals (CIs) for the association between number of
      sexual partners and PCa by fitting logistic regression models, stratified by MSMB
      genotype, and adjusted for age, family history of PCa, and PCa screening history
      among 1,239 incident cases and 1,232 controls. RESULTS: Compared with 1-4 female
      sexual partners, men with >= 15 such partners who carried the variant T allele of
      rs10993994 were at increased risk for PCa (OR = 1.32; 95% CI, 1.03-1.71); no
      association was observed in men with the CC genotype (OR = 1.03; 95% CI, 0.73
      1.46; P = 0.05 for interaction). Similar estimates were observed for total sexual
      partners (any T allele OR = 1.37; 95% CI, 1.07-1.77; CC genotype OR = 1.11; 95%
      CI, 0.79-1.55; P = 0.06 for interaction). CONCLUSIONS: The rs10993994 genotype in
      the MSMB gene modifies the association between number of sexual partners and PCa
      risk. These findings support a hypothesized biological mechanism whereby
      prostatic infection/inflammation may enhance risk of PCa.

PMID- 24037735
TI  - Long-term cardiac safety and outcomes of dose-dense doxorubicin and
      cyclophosphamide followed by paclitaxel and trastuzumab with and without
      lapatinib in patients with early breast cancer.
AB  - BACKGROUND: The authors have previously reported 2 consecutive phase 2 trials in
      patients with early breast cancer that overexpresses human epidermal growth
      factor receptor 2 (HER2) to assess the feasibility of incorporating anti-HER2
      therapies into dose-dense (dd) chemotherapy regimens. The incidence of congestive
      heart failure (CHF) at a median follow-up of 2 years was 1.4% and 3.2%,
      respectively. METHODS: In trial A, patients received dd doxorubicin and
      cyclophosphamide (AC)->paclitaxel (T) (each given every 2 weeks) * 4 with
      trastuzumab (H) given * 1 year. In trial B, weekly T (weekly * 12) was
      substituted for ddT and lapatinib * 1 year was added. Herein, the authors report
      the longer-term incidence of CHF and distant disease-free survival (DDFS).
      RESULTS: From January 2005 to May 2008, 165 patients enrolled (median age, 46
      years, with a median left ventricular ejection fraction of 68% [range, 52%-81%]),
      17%of whom had previous hypertension. With a median follow-up of 84 months (trial
      A) and 57 months (trial B), 1 additional patient developed CHF. Therefore, the
      cumulative incidence of CHF was 1.4% (95% confidence interval [95% CI], 1.36%
      7.7%) for trial A and 4.2% (95% CI, 4.2%-10.4%) for trial B. The 5-year DDFS for
      trials A and B was 92% (95% CI, 83%-97%) and 89% (95% CI, 81%-94%), respectively.
      CONCLUSIONS: Longer follow-up of these 2 studies has demonstrated that ddAC->TH
      only or with lapatinib is associated with a low risk of CHF and promising DDFS in
      patients with early breast cancer.

PMID- 24037736
TI  - Gastric cancer patients with Helicobacter pylori infection have a poor prognosis.
AB  - BACKGROUND AND OBJECTIVES: Gastric cancer patients with Helicobacter pylori
      infection had been reported to have a better prognosis. However, this finding is
      still controversial. Our research aims to investigate the influence of H. pylori
      infection on the prognosis of gastric cancer patients who underwent surgery.
      METHODS: The H. pylori infection status of 162 consecutive gastric cancer
      patients who underwent surgery was assessed in their tumor samples by
      immunohistochemical staining. Univariate and multivariable analysis were employed
      to investigate the potential impact of H. pylori infection status on the gastric
      cancer-specific survival and relapse-free survival of the patients. RESULTS: The
      median follow-up period was 35.3 months (range, 1.7-71.9). Gastric cancer
      specific survival was 30.2 months (95% CI 24.8-35.6) and relapse-free survival
      was 28.7 months (23.5-34) in H. pylori positive patients, compared with 39.8
      months (34.8-44.7) and 38.1 months (33-43.2), respectively in H. pylori negative
      patients (P = 0.01 and P = 0.011, respectively. Multivariable analysis showed
      positive H. pylori infection is an independent prognostic factor for gastric
      cancer-specific survival (hazard ratio 1.71 [95% CI 1.11-2.66]) and relapse-free
      survival (hazard ratio 1.68 [95% CI 1.05-2.69]). CONCLUSION: Gastric cancer
      patients with H. pylori infection have poor gastric cancer-specific survival and
      relapse-free survival. Our finding suggested that the H. pylori infection could
      be an indicator for prognosis of gastric cancer patients.

PMID- 24037737
TI  - Intrathyroidal parathyroid carcinoma mimicking a thyroid nodule in a MEN type 1
      patient.
AB  - A 59-year-old woman with classic manifestations of hyperparathyroidism associated
      with multiple endocrine neoplasia type 1 presented with a right adrenal mass and
      two pituitary microadenomas on imaging studies. For evaluation of hypercalcemia,
      (99m) Tc-MIBI scintigraphy was done and showed focal uptake at the thyroid level
      of the right anterior neck. Subsequent neck sonography showed several thyroid
      nodules, but there was no parathyroid tumor. Percutaneous fine-needle aspiration
      of the dominant thyroid nodule indicated a follicular nodule. After surgery,
      final histopathology revealed intrathyroidal parathyroid carcinoma. This case
      illustrates the difficulty in diagnosing parathyroid carcinoma via fine-needle
      aspiration.

PMID- 24037738
TI  - Plateau effect of prostate cancer risk-associated SNPs in discriminating prostate
      biopsy outcomes.
AB  - BACKGROUND: Additional prostate cancer (PCa) risk-associated single nucleotide
      polymorphisms (SNPs) continue to be identified. It is unclear whether addition of
      newly identified SNPs improves the discriminative performance of biopsy outcomes
      over previously established SNPs. METHODS: A total of 667 consecutive patients
      that underwent prostate biopsy for detection of PCa at Huashan Hospital and
      Changhai Hospital, Shanghai, China were recruited. Genetic scores were calculated
      for each patient using various combinations of 29 PCa risk-associated SNPs.
      Performance of these genetic scores for discriminating prostate biopsy outcomes
      were compared using the area under a receiver operating characteristic curve
      (AUC). RESULTS: The discriminative performance of genetic score derived from a
      panel of all 29 SNPs (24 previous and 5 new) was similar to that derived from the
      24 previously established SNPs, the AUC of which were 0.60 and 0.61, respectively
      (P = 0.72). When SNPs with the strongest effect on PCa risk (ranked based on
      contribution to the total genetic variance from an external study) were
      sequentially added to the models for calculating genetic score, the AUC gradually
      increased and peaked at 0.62 with the top 13 strongest SNPs. Under the 13-SNP
      model, the PCa detection rate was 21.52%, 36.74%, and 51.98%, respectively for
      men with low (<0.5), intermediate (0.5-1.5), and high (>1.5) genetic score, P
      trend = 9.91 * 10(-6). CONCLUSION: Genetic score based on PCa risk-associated
      SNPs implicated to date is a significant predictor of biopsy outcome. Additional
      small-effect PCa risk-associated SNPs to be discovered in the future are unlikely
      to further improve predictive performance.

PMID- 24037740
TI  - TWEAK transactivation of the epidermal growth factor receptor mediates renal
      inflammation.
AB  - TWEAK, a member of the TNF superfamily, binds to the Fn14 receptor, eliciting
      biological responses. EGFR signalling is involved in experimental renal injury.
      Our aim was to investigate the relationship between TWEAK and EGFR in the kidney.
      Systemic TWEAK administration into C57BL/6 mice increased renal EGFR
      phosphorylation, mainly in tubular epithelial cells. In vitro, in these cells
      TWEAK phosphorylated EGFR via Fn14 binding, ADAM17 activation and subsequent
      release of the EGFR ligands HB-EGF and TGFalpha. In vivo the EGFR kinase
      inhibitor Erlotinib inhibited TWEAK-induced renal EGFR activation and downstream
      signalling, including ERK activation, up-regulation of proinflammatory factors
      and inflammatory cell infiltration. Moreover, the ADAM17 inhibitor WTACE-2 also
      prevented those TWEAK-induced renal effects. In vitro TWEAK induction of
      proinflammatory factors was prevented by EGFR, ERK or ADAM17 inhibition. In
      contrast, EGFR transactivation did not modify TWEAK-mediated NF-kappaB
      activation. Our data suggest that TWEAK transactivates EGFR in the kidney,
      leading to modulation of downstream effects, including ERK activation and
      inflammation, and suggest that inhibition of EGFR signalling could be a novel
      therapeutic tool for renal inflammation.

PMID- 24037739
TI  - Horizontal gene transfer in eukaryotes: the weak-link model.
AB  - The significance of horizontal gene transfer (HGT) in eukaryotic evolution
      remains controversial. Although many eukaryotic genes are of bacterial origin,
      they are often interpreted as being derived from mitochondria or plastids.
      Because of their fixed gene pool and gene loss, however, mitochondria and
      plastids alone cannot adequately explain the presence of all, or even the
      majority, of bacterial genes in eukaryotes. Available data indicate that no
      insurmountable barrier to HGT exists, even in complex multicellular eukaryotes.
      In addition, the discovery of both recent and ancient HGT events in all major
      eukaryotic groups suggests that HGT has been a regular occurrence throughout the
      history of eukaryotic evolution. A model of HGT is proposed that suggests both
      unicellular and early developmental stages as likely entry points for foreign
      genes into multicellular eukaryotes.

PMID- 24037741
TI  - An integrated model for developing research skills in an undergraduate medical
      curriculum: appraisal of an approach using student selected components.
AB  - Student selected components (SSCs), at that time termed special study modules,
      were arguably the most innovative element in Tomorrow's Doctors (1993), the
      document from the General Medical Council that initiated the modernization of
      medical curricula in the UK. SSCs were proposed to make up one-third of the
      medical curriculum and provide students with choice, whilst allowing individual
      schools autonomy in how SSCs were utilized. In response, at the University of
      Edinburgh the undergraduate medical curriculum provides an integrated and
      sequential development and assessment of research skill learning outcomes, for
      all students in the SSC programme. The curriculum contains SSCs which provide
      choice to students in all 5 years. There are four substantial timetabled SSCs
      where students develop research skills in a topic and speciality of their choice.
      These SSCs are fully integrated and mapped with core learning outcomes and
      assessment, particularly with the 'Evidence-Based Medicine and Research'
      programme theme. These research skills are developed incrementally and applied
      fully in a research project in the fourth year. One-third of students also
      perform an optional intercalated one-year honours programme between years 2 and
      3, usually across a wide range of honours schools at the biomedical science
      interface. Student feedback is insightful and demonstrates perceived attainment
      of research competencies. The establishment of these competencies is discussed in
      the context of enabling junior graduate doctors to be effective and confident at
      utilizing their research skills to effectively practice evidence-based medicine.
      This includes examining their own practice through clinical audit, developing an
      insight into the complexity of the evidence base and uncertainty, and also
      gaining a view into a career as a clinical academic. 

PMID- 24037742
TI  - Key factors in work engagement and job motivation of teaching faculty at a
      university medical centre.
AB  - This study reports about teacher motivation and work engagement in a Dutch
      University Medical Centre (UMC). We examined factors affecting the motivation for
      teaching in a UMC, the engagement of UMC Utrecht teaching faculty in their work,
      and their engagement in teaching compared with engagement in patient care and
      research. Based on a pilot study within various departments at the UMCU, a survey
      on teaching motivation and work engagement was developed and sent to over 600
      UMCU teachers. About 50 % responded. Work engagement was measured by the Utrecht
      Work Engagement Scale, included in this survey. From a list of 22 pre-defined
      items, 5 were marked as most motivating: teaching about my own speciality,
      noticeable appreciation for teaching by my direct superior, teaching small
      groups, feedback on my teaching performance, and freedom to determine what I
      teach. Feedback on my teaching performance showed the strongest predictive value
      for teaching engagement. Engagement scores were relatively favourable, but
      engagement with patient care was higher than with research and teaching. Task
      combinations appear to decrease teaching engagement. Our results match with self
      determination theory and the job demands-resources model, and challenge the
      policy to combine teaching with research and patient care. 

PMID- 24037743
TI  - Portable NIR-AOTF spectroscopy combined with winery FTIR spectroscopy for an
      easy, rapid, in-field monitoring of Sangiovese grape quality.
AB  - BACKGROUND: A near infrared acousto-optically tunable filter (NIR-AOTF)
      spectrophotometer was tested for three seasons on four different vineyards with
      the aim of monitoring the ripening evolution of the Italian red wine grape
      variety Sangiovese. Predictive models for the estimation of several enological
      parameters were carried out applying the partial least squares chemometric
      approach. Reference analysis was conducted using Fourier transform infrared
      spectroscopy (FTIR). Spectral detections were obtained working on whole grape
      berries. A global set of 96 samples (n = 76 in 2009, and n = 20 in 2010) each one
      represented by 100 intact grape berries was tested. Finally, in 2011, an external
      validation on an independent data set of 25 samples (50 grape berries per set)
      was carried out. RESULTS: Coupling the two spectroscopic applications, the
      following enological parameters were tested:  degrees Brix,  degrees Babo, total
      sugars (g L(-1)), glucose (g L(-1)), fructose (g L(-1)), density (g mL(-1)),
      titratable acidity (g L(-1)), tartaric acid (g L(-1)), pH, malic acid (g L(-1)),
      gluconic acid (g L(-1)), assumable nitrogen (mg L(-1) ), anthocyanins (mg L(-1)),
      and total phenols (mg L(-1)). NIR-AOTF spectroscopy was able to predict with a
      high correlation versus the measured data:  degrees Brix,  degrees Babo, total
      sugars, glucose, fructose and density. The coefficient of determination (R(2))
      and the standard error in prediction were: 0.93 and 0.73 for  degrees Brix; 0.93
      and 0.62 for  degrees Babo; 0.94 and 7.39 g L(-1) for total sugars; 0.93 and 5.39
      g L(-1) for glucose; 0.92 and 5.07 g L(-1) for fructose; and 0.91 and 0.004 g mL(
      1) for density, respectively. Significant correlations were found in prediction
      for tartaric acid and pH value. Promising validation results were recorded for
      anthocyanins and total phenols, even though predictive models were affected by
      the method of sample preparation in compound extraction. CONCLUSIONS: This study
      shows how NIR-AOTF spectroscopy can be used in viticulture to investigate,
      directly in-field, the most significant markers of ripening evolution and of
      Sangiovese grape quality definition. The use of the vinery FTIR spectroscopy
      provided the reduction of the time required by reference analysis, with the big
      advantage of obtaining many different parameters in just a few seconds and
      allowing easier calibration of the NIR spectrometer.

PMID- 24037744
TI  - Dramatic substituent effects on the mechanisms of nucleophilic attack on Se-S
      bridges.
AB  - The reactions of XSeSX, XSeSY, and YSeSX (X, Y = CH3, NH2, OH, F) with F(-) and
      CN(-) nucleophiles have been investigated by means of B3PW91/6-311+G(2df,p) and
      G4 calculations. In systems where the two substituents are not identical (XSeSY),
      the more stable of the two possible isomers corresponds to those in which the
      most electronegative substituent is attached to Se. Nucleophilic attack takes
      place at Se, independent of the nature of the nucleophile, with the only
      exception being XSeSF (X = CH3 , NH2 , OH), in which case the attack occurs at S.
      In agreement with recent results for disulfide and diselenide linkages, the
      mechanisms leading to Se-S bond cleavage are not always the more favorable ones
      because for highly electronegative substituents the most favorable process is
      fission of the chalcogen-substituent bond. These dissimilarities in the observed
      reactivity pattern as a function of the electronegativity of the substituents are
      due to the fact that the sigma-type Se-S antibonding orbital, which for low
      electronegative substituents is the lowest unnoccupied molecular orbital (LUMO),
      becomes strongly destabilized when the electronegativity of the substituent
      increases, and is replaced by an antibonding pi-type Se-X (or S-X) orbital. In
      contrast, however, with what has been found for disulfide and diselenide
      derivatives, the observed reactivity does not change with the nature of the
      nucleophile. The activation strain model provides interesting insight into these
      processes, showing that in most cases the activation barriers are the consequence
      of subtle differences in the strain or in the interaction energies.

PMID- 24037746
TI  - Practices of anesthesiologists to alleviate anxiety in children and adolescents
      in Canada.

PMID- 24037745
TI  - Muscle coactivation: a generalized or localized motor control strategy?
AB  - INTRODUCTION: We examined generalized versus joint-specific influences on muscle
      coactivation. METHODS: Muscle coactivation was assessed during maximal isometric
      and isokinetic knee and elbow joint extension moments in 48 healthy subjects (27
      men). Local (joint-specific) and generalized (person-specific) contributions were
      examined using a combination of statistical tests, including regression with
      generalized estimating equations (GEEs), exploratory factor analysis, and cluster
      analysis. RESULTS: GEEs produced similar significant coefficients for gender and
      joint; contraction type and test condition (angle or velocity) were not
      significant. Factor analysis indicated 2 joint-based factors, and cluster
      analysis indicated 2 groups of individuals, those with and without elevated
      coactivation at the knee and elbow. Women exhibited greater coactivation at both
      joints, but no consistent influences of angle or velocity were observed at either
      joint. CONCLUSION: Muscle coactivation is a neuromuscular control response
      determined by local, joint-specific, and generalized, individual-specific
      influences.

PMID- 24037747
TI  - Maternal cardiac arrest in a tertiary care centre during 1989-2011: a case
      series.
AB  - PURPOSE: To review and report maternal and neonatal outcomes after cardiac arrest
      during pregnancy in a large tertiary care centre and to consider steps to improve
      the outcomes. CLINICAL FEATURES: We performed a retrospective chart review of
      maternal cardiac arrest in the Mount Sinai Hospital, University of Toronto health
      records database for the period 1989-2011. Five cases were identified for an
      incidence of 1:24,883 deliveries (0.004%). Four of the five women were obese and
      older than 35 yr. Two women had pre-existing cardiac conditions, and one had
      placenta accrete. All three underwent perimortem Cesarean delivery (PMCD), but
      none of these procedures was done within the recommended time of the "four-minute
      rule." Two of the three women had repeated arrests and subsequently died. The
      other two women were in labour, received regional analgesia, and had assisted
      vaginal deliveries. Both of these patients survived, and all survivors (mothers
      and neonates) were neurologically intact. Four of five neonates survived. The
      etiology of the cardiac arrest was indeterminate in all five cases, although
      suspected amniotic fluid embolism was considered the most likely contributing
      factor in the majority of cases. Overall, the quality of the charting was
      inconsistent and incomplete. CONCLUSIONS: This series of five cases highlights
      the challenges to meeting the rule of initiating PMCD within four minutes of
      maternal cardiac arrest onset. We suggest focusing on the quality of ongoing
      resuscitation efforts and early delivery as our experience shows that mother and
      neonate can survive beyond five minutes after arrest. Improved documentation and
      creation of a national database for these rare events should be considered.

PMID- 24037748
TI  - Cohort study of cases with prolonged tracheal extubation times to examine the
      relationship with duration of workday.
AB  - PURPOSE: The economics of the use of an anesthetic drug or device that produces
      benefit through reduction in operating room (OR) time depends on the day of the
      week and the total hours of surgical cases in the OR in which they are performed.
      Principally, this has to do with different durations of the regularly scheduled
      workday in the ORs within and among hospitals. We tested hypotheses relevant to
      the economic benefit of avoiding prolonged tracheal extubation times. METHODS:
      Observational data were obtained from a multiple-specialty academic tertiary
      hospital that uses an anesthesia information management system. Prolonged
      tracheal extubation times were considered those with tracheal extubations
      occurring 15 min or more after the end of surgery. The assessment of prolonged
      tracheal extubation times was limited to cases for which the patient's trachea
      was intubated and extubated while physically in the OR. Percentages were
      calculated for each of n = 39 four-week periods. Results are reported as mean
      (standard error of the mean) of these percentages, and the phrases "at
      most/least" are used to refer to the corresponding 95% confidence limits.
      RESULTS: At most, 6.1% [mean 5.5 (0.3)%] of the prolonged tracheal extubation
      times were attributable to cases that did not end during regular workdays from
      7:00 AM-10:59 PM. At least 55.6% of prolonged tracheal extubation times occurred
      during cases on regular workdays and in an OR with more than eight hours of cases
      and turnovers [mean 57.0 (0.9)%; P < 0.0001]. This percentage was 23.8 (0.8)%
      larger than for all other cases. CONCLUSIONS: In the absence of an accurate
      facility-specific cost analysis, prolonged tracheal extubation times should not
      be treated as fixed costs but as resulting in proportionally increased OR
      variable costs.

PMID- 24037749
TI  - A case of acute respiratory distress syndrome responsive to methylene blue during
      a carcinoid crisis.
AB  - PURPOSE: In a carcinoid crisis, numerous vasoactive agents, such as bradykinin
      precursors, serotonin, and histamine, are secreted by tumour cells. Bradykinin
      has been shown to increase pulmonary vascular permeability and hypotension in
      animal models; however, little is known about its in vivo effects or targeted
      pharmacotherapy in a carcinoid crisis. We describe a case of acute respiratory
      distress syndrome (ARDS) in a carcinoid crisis refractory to conventional
      antiserotonin and antihistamine therapies. CLINICAL FEATURES: A 56-yr-old male
      with known liver metastases and previous resection of a small intestinal
      carcinoid tumour in 1991 underwent successful tricuspid and pulmonary valve
      replacements. On postoperative day 10, he developed hypotension, a fever,
      leukocytosis, and flushing. His hypotension was treated with a 200 MUg octreotide
      iv bolus followed by a 150 MUg.hr(-1) infusion, vasopressin, norepinephrine, and
      hydrocortisone. He also required tracheal intubation for ARDS (Pa02:FI02 ratio
      96). After 72 hr of broad spectrum antibiotics and no clinical improvement,
      antiserotonin and antihistamine therapies were augmented with cyproheptadine,
      ranitidine, and serial octreotide boluses with an infusion of 1,500 MUg.hr(-1).
      These interventions improved his oxygenation (Pa02:F i 02 ratio 162) and reduced
      his norepinephrine requirements. Following a methylene blue bolus (1 mg.kg(-1))
      and 12-hr infusion (0.5 mg.kg(-1).hr(-1)), all vasopressors were discontinued and
      his oxygenation improved (Pa02:F i 02 ratio 297). CONCLUSION: In a patient with a
      carcinoid crisis and ARDS refractory to conventional therapies, substantial
      hemodynamic and oxygenation improvements were observed following methylene blue
      administration. This case highlights the potential pathophysiologic role of
      bradykinin and methylene blue as an adjunct therapeutic option in carcinoid
      crises.

PMID- 24037750
TI  - Case of postpartum Parsonage-Turner syndrome.

PMID- 24037751
TI  - Alcohol consumption and breast cancer risk among women from five ethnic groups
      with light to moderate intakes: the Multiethnic Cohort Study.
AB  - Higher alcohol consumption, even at moderate levels, has been associated with an
      increased risk of breast cancer in epidemiological studies. However, prior
      studies were conducted in mostly white populations. To assess the relationship of
      alcohol consumption to postmenopausal breast cancer risk in a multiethnic
      population of largely never, light or moderate drinkers, we prospectively
      examined the association in 85,089 women enrolled in the Multiethnic Cohort in
      Hawaii and California. During a mean follow-up of 12.4 years, 3,885 incident
      invasive breast cancer cases were identified. Hazard ratios (HRs) and 95%
      confidence intervals (CIs) were estimated using Cox proportional hazard models,
      controlling for potential confounders. Higher alcohol consumption was associated
      with increased risk of breast cancer: compared to nondrinkers, HRs were 1.23 (95%
      CI: 1.06-1.42), 1.21 (95% CI: 1.00-1.45), 1.12 (95% CI: 0.95-1.31) and 1.53 (95%
      CI: 1.32-1.77) for 5-9.9, 10-14.9, 15-29.9 and >= 30 g/day of alcohol,
      respectively. The positive association was seen in African American, Japanese
      American, Latino and white, but not in Native Hawaiian women, and in those with
      tumors that were both positive and negative for estrogen and progesterone
      receptors (ER/PR). This prospective study supports previous findings that light
      to moderate alcohol consumption increases breast cancer risk, and demonstrates
      this association in several ethnic groups besides whites, independent of ER/PR
      status.

PMID- 24037753
TI  - Endometrial adult/progenitor stem cells: pathogenetic theory and new
      antiangiogenic approach for endometriosis therapy.
AB  - The cyclical arrival of endometrial cells into the abdominal cavity through
      retrograde flux at menstruation represents the etiopathogenetic basis of
      endometriosis. The endometrium has peculiar regenerative properties linked to the
      presence of adult stem cells similar to mesenchymal stem cells (MSCs). Once in
      the abdominal cavity, these MSCs could proliferate, invade, and differentiate
      into endometrial cells, finally generating ectopic implants. As only
      differentiated endometrial cells, and not endometrial MSCs, possess steroid
      hormone receptors, MSCs could be responsible for the high rate of
      persistence/recurrence of the disease after hypoestrogenism-inducing therapies.
      Even angiogenesis promoted by MSCs could play an important role, as survival and
      proliferation of endometriotic tissue depend on the formation of new blood
      vessels. Inhibition of angiogenesis represents, in fact, a new, promising
      therapeutic approach for the disease. Further, medications directly targeting
      endometriosis MSCs could be effective, alone or in association with hormonal
      treatments, in increasing the success of medical treatment. 

PMID- 24037752
TI  - Oncogenic mutations in cervical cancer: genomic differences between
      adenocarcinomas and squamous cell carcinomas of the cervix.
AB  - BACKGROUND: Cervical cancer is the second leading cause of cancer deaths among
      women worldwide. The objective of this study was to describe the most common
      oncogenic mutations in cervical cancers and to explore genomic differences
      between the 2 most common histologic subtypes: adenocarcinoma and squamous cell
      carcinoma. METHODS: A high-throughput genotyping platform, termed Oncomap, was
      used to interrogate 80 cervical tumors for 1250 known mutations in 139 cancer
      genes. Samples were analyzed using a mass spectrometry-based genotyping platform
      and were validated using orthogonal chemistry. Epidermal growth factor receptor
      (EGFR) mutations were further validated by massive parallel sequencing. Human
      papilloma virus (HPV) genotyping also was performed. RESULTS: Validated mutations
      were detected in 48 of 80 tumors (60%) examined. The highest mutation rates were
      in the genes phosphatidylinositol 3-kinase, catalytic subunit alpha (PIK3CA)
      (31.3%); Kirsten rat sarcoma viral oncogene homolog (KRAS) (8.8%); and EGFR
      (3.8%). PIK3CA mutation rates did not differ significantly between
      adenocarcinomas and squamous cell carcinomas (25% vs 37.5%, respectively; P =
      .33). In contrast, KRAS mutations were identified only in adenocarcinomas (17.5%
      vs 0%; P = .01), and a novel EGFR mutation was detected only in squamous cell
      carcinomas (0% vs 7.5%; P = .24). There were no associations between HPV-16 or
      HPV-18 and somatic mutations or overall survival. In adjusted analyses, PIK3CA
      mutations were associated with shorter survival (67.1 months vs 90.3 months;
      hazard ratio, 9.1; 95% confidence interval, 2.8-29.5 months; P < .001).
      CONCLUSIONS: Cervical cancers harbor high rates of potentially targetable
      oncogenic mutations. In addition, cervical squamous cell carcinoma and
      adenocarcinoma have distinct molecular profiles, suggesting that clinical
      outcomes may be improved with the use of more tailored treatment strategies,
      including PI3K and MEK inhibitors.

PMID- 24037754
TI  - Moral disengagement among children and youth: a meta-analytic review of links to
      aggressive behavior.
AB  - A growing body of research has demonstrated consistent links between Bandura's
      theory of moral disengagement and aggressive behavior in adults. The present meta
      analysis was conducted to summarize the existing literature on the relation
      between moral disengagement and different types of aggressive behavior among
      school-age children and adolescents. Twenty-seven independent samples with a
      total of 17,776 participants (aged 8-18 years) were included in the meta
      analysis. Results indicated a positive overall effect (r = .28, 95% CI [.23,
      .32]), supporting the hypothesis that moral disengagement is a significant
      correlate of aggressive behavior among children and youth. Analyses of a priori
      moderators revealed that effect sizes were larger for adolescents as compared to
      children, for studies that used a revised version of the original Bandura scale,
      and for studies with shared method variance. Effect sizes did not vary as a
      function of type of aggressive behavior, gender, or publication status. Results
      are discussed within the extant literature on moral disengagement and future
      directions are proposed.

PMID- 24037755
TI  - Admixture mapping of prostate cancer in African Americans participating in the
      North Carolina-Louisiana Prostate Cancer Project (PCaP).
AB  - BACKGROUND: Few genetic risk factors have been uncovered that contribute
      specifically to the racial disparity in prostate cancer (CaP) observed in African
      Americans (AA). With the advent of ancestry informative marker (AIM) single
      nucleotide polymorphism (SNP) panels and powerful genetic strategies such as
      mapping by admixture linkage disequilibrium (MALD) it is possible to discover
      genes that underlie ethnic variation in disease risk. METHODS: One thousand one
      hundred thirty AA CaP cases enrolled in the North Carolina-Louisiana Prostate
      Cancer Project (PCaP) were genotyped using a 1,509 AIM SNP panel. MALD was
      performed using ADMIXMAP to test for linkage between CaP risk and ancestry
      estimates at each AIM SNP. RESULTS: The largest increase of African ancestry was
      observed at marker rs12543473 (P = 0.0011), located on chromosome 8q24.21, and
      the greatest excess of European ancestry was observed at marker rs10768140 (P =
      0.0004) at chromosome 11p13. CONCLUSIONS: The study confirmed the 8q24 risk loci
      and identified a novel genomic region on 11p13 that is associated with CaP risk.
      These findings should be replicated in larger AA populations and combined with
      fine mapping data to further refine the novel 11p13 CaP risk loci.

PMID- 24037756
TI  - Computational protein design: the Proteus software and selected applications.
AB  - We describe an automated procedure for protein design, implemented in a flexible
      software package, called Proteus. System setup and calculation of an energy
      matrix are done with the XPLOR modeling program and its sophisticated command
      language, supporting several force fields and solvent models. A second program
      provides algorithms to search sequence space. It allows a decomposition of the
      system into groups, which can be combined in different ways in the energy
      function, for both positive and negative design. The whole procedure can be
      controlled by editing 2-4 scripts. Two applications consider the tyrosyl-tRNA
      synthetase enzyme and its successful redesign to bind both O-methyl-tyrosine and
      D-tyrosine. For the latter, we present Monte Carlo simulations where the D
      tyrosine concentration is gradually increased, displacing L-tyrosine from the
      binding pocket and yielding the binding free energy difference, in good agreement
      with experiment. Complete redesign of the Crk SH3 domain is presented. The top
      10000 sequences are all assigned to the correct fold by the SUPERFAMILY library
      of Hidden Markov Models. Finally, we report the acid/base behavior of the SNase
      protein. Sidechain protonation is treated as a form of mutation; it is then
      straightforward to perform constant-pH Monte Carlo simulations, which yield good
      agreement with experiment. Overall, the software can be used for a wide range of
      application, producing not only native-like sequences but also thermodynamic
      properties with errors that appear comparable to other current software packages.

PMID- 24037757
TI  - Inflammatory nodules following soft tissue filler use: a review of causative
      agents, pathology and treatment options.
AB  - Nodule development is a common complication following the use of fillers for soft
      tissue augmentation and is commonly categorized as inflammatory or non
      inflammatory in nature. Inflammatory nodules may appear anywhere from days to
      years after treatment, whereas non-inflammatory nodules are typically seen
      immediately following implantation and are usually secondary to improper
      placement of the filler. Although inflammatory nodules are more common with
      permanent fillers such as silicone, inflammatory nodule development following
      administration of temporary fillers such as hyaluronic acid and collagen has also
      been reported. Treated many times with corticosteroids due to their anti
      inflammatory properties, inflammatory nodules may be secondary to infection or
      biofilm formation, warranting the use of alternative agents. Appropriate and
      prompt diagnosis is important in avoiding delay of treatment or long-term
      complications for the patient. This paper addresses the etiology, development,
      and studied treatment options available for inflammatory nodules secondary to
      each of the major classes of fillers. With this knowledge, practitioners may
      expeditiously recognize and manage this common side effect and thus maximize
      functional and aesthetic benefit. 

PMID- 24037758
TI  - Loss expression of PHLPP1 correlates with lymph node metastasis and exhibits a
      poor prognosis in patients with gastric cancer.
AB  - BACKGROUND: PHLPP1 functions as an antitumor factor in several human cancers, but
      the expression pattern and clinical significance of PHLPP1 in gastric cancer have
      yet to be determined. The aim of this study is to assess the expression of PHLPP1
      in gastric cancer and its impact on the prognosis of patients with gastric
      cancer. METHODS: A total of 202 consecutive patients with gastric cancer who had
      undergone gastrectomy were enrolled in this study. The expressions of PHLPP1 were
      assessed by immunohistochemistry method. Survival analysis according to PHLPP1
      expression was calculated. RESULTS: The positive rates of PHLPP1 protein in
      primary gastric cancer tissues and metastatic lymph nodes were significantly
      lower than in normal stomach mucosa tissues (56.9% vs. 96.7%, 38.8% vs. 96.7%,
      both P < 0.001). The overall survival (OS) time and relapse-free survival (RFS)
      time in PHLPP1-positive patients were significantly longer than in PHLPP1
      negative patients (both P < 0.001). Moreover, PHLPP1 was an independent
      prognostic factor for OS and RFS of gastric cancer patients (HR 0.55, 95% CI 0.36
      0.85, P = 0.007; HR 0.52, 95% CI 0.31-0.87, P = 0.013; respectively).
      CONCLUSIONS: The loss expression of PHLPP1 was observed in gastric cancer and
      PHLPP1 is an independent prognostic factor for patients with gastric cancer.

PMID- 24037759
TI  - The insulin receptor changes conformation in unforeseen ways on ligand binding:
      sharpening the picture of insulin receptor activation.
AB  - Unraveling the molecular detail of insulin receptor activation has proved
      challenging, but a major advance is the recent determination of crystallographic
      structures of insulin in complex with its primary binding site on the receptor.
      The current model for insulin receptor activation is that two distinct surfaces
      of insulin monomer engage sequentially with two distinct binding sites on the
      extracellular surface of the insulin receptor, which is itself a disulfide-linked
      (alphabeta)2 homodimer. In the process, conformational changes occur both within
      the hormone and the receptor, the latter resulting in the disruption of the
      intracellular interactions that hold the kinase domains in their basal state and
      in the initiation of the phosphorylation events that drive insulin signaling. The
      purpose of this paper is to summarize the extant structural data relating to
      hormone binding and how it effects receptor activation, as well as to discuss the
      issues that remain unresolved.

PMID- 24037760
TI  - Massively-parallel sequencing assists the diagnosis and guided treatment of
      cancers of unknown primary.
AB  - The clinical management of patients with cancer of unknown primary (CUP) is
      hampered by the absence of a definitive site of origin. We explored the utility
      of massively-parallel (next-generation) sequencing for the diagnosis of a primary
      site of origin and for the identification of novel treatment options. DNA
      enrichment by hybridization capture of 701 genes of clinical and/or biological
      importance, followed by massively-parallel sequencing, was performed on 16 CUP
      patients who had defied attempts to identify a likely site of origin. We obtained
      high quality data from both fresh-frozen and formalin-fixed, paraffin-embedded
      samples, demonstrating accessibility to routine diagnostic material. DNA copy
      number obtained by massively-parallel sequencing was comparable to that obtained
      using oligonucleotide microarrays or quantitatively hybridized fluorescently
      tagged oligonucleotides. Sequencing to an average depth of 458-fold enabled
      detection of somatically acquired single nucleotide mutations, insertions,
      deletions and copy-number changes, and measurement of allelic frequency. Common
      cancer-causing mutations were found in all cancers. Mutation profiling revealed
      therapeutic gene targets and pathways in 12/16 cases, providing novel treatment
      options. The presence of driver mutations that are enriched in certain known
      tumour types, together with mutational signatures indicative of exposure to
      sunlight or smoking, added to clinical, pathological, and molecular indicators of
      likely tissue of origin. Massively-parallel DNA sequencing can therefore provide
      comprehensive mutation, DNA copy-number, and mutational signature data that are
      of significant clinical value for a majority of CUP patients, providing both
      cumulative evidence for the diagnosis of primary site and options for future
      treatment.

PMID- 24037761
TI  - Interaction of Yersinia enterocolitica biovar 1A with cultured cells in vitro
      does not reflect the two previously identified clonal groups.
AB  - Yersinia enterocolitica biovar 1A strains have been delineated into two clonal
      groups (A and B) based on repetitive extragenic palindrome- and enterobacterial
      repetitive intergenic consensus-PCR genotyping. The present study investigated
      the interaction of Y. enterocolitica biovar 1A strains with cultured cells in
      vitro by their ability to adhere, invade and survive within these cells. The
      response of macrophages to these strains was also studied by quantifying the
      expression of inducible nitric oxide synthase, production of nitric oxide and
      cytokines, and activation of NFkappaB. The survival rate of clonal group B
      strains inside macrophages was significantly higher than that of clonal group A
      strains. In addition, strains harbouring the fepA gene showed better survival
      inside macrophages. However, the production of nitric oxide and cytokines and
      activation of NFkappaB did not show any significant differences between the two
      clonal groups. In this study, interaction of Y. enterocolitica biovar 1A with
      cultured cells in vitro did not reflect the previously identified clonal groups,
      but was more dependent on the characteristics of the individual strains.
      Therefore, a combination of genotype and phenotype data must be used to
      characterize this extremely heterogeneous organism. 

PMID- 24037762
TI  - Effect of generalized joint hypermobility on knee function and muscle activation
      in children and adults.
AB  - INTRODUCTION: We investigated muscle activation strategy and performance of knee
      extensor and flexor muscles in children and adults with generalized joint
      hypermobility (GJH) and compared them with controls. METHODS: Muscle activation,
      torque steadiness, electromechanical delay, and muscle strength were evaluated in
      39 children and 36 adults during isometric knee extension and flexion. Subjects
      performed isometric maximum contractions, submaximal contractions at 25% maximum
      voluntary contraction (MVC), and explosive contractions. RESULTS: Agonist
      activation was reduced, and coactivation ratio was greater in GJH during knee
      flexion compared with controls. Torque steadiness was impaired in adults with GJH
      during knee flexion. No effect of GJH was found on muscle strength or
      electromechanical delay. Correlation analysis revealed an association between GJH
      severity and function in adults. CONCLUSIONS: The results indicate that muscle
      activation strategy and quality of force control were significantly affected in
      adults with GJH during knee flexion, whereas only muscle activation strategy was
      affected in children with GJH.

PMID- 24037763
TI  - Aluminium-phosphate interactions in the rhizosphere of two bean species:
      Phaseolus lunatus L. and Phaseolus vulgaris L.
AB  - BACKGROUND: Plants differ in their response to high aluminium (Al)
      concentrations, which typically cause toxicity in plants grown on acidic soils.
      The response depends on plant species and environmental conditions such as
      substrate and cultivation system. The present study aimed to assess Al-phosphate
      (P) dynamics in the rhizosphere of two bean species, Phaseolus vulgaris L. var.
      Red Kidney and Phaseolus lunatus L., in rhizobox experiments. RESULTS: Root
      activity of the bean species induced up to a sevenfold increase in exchangeable
      Al and up to a 30-fold decrease in extractable P. High soluble Al concentrations
      triggered the release of plant-specific carboxylates, which differed between soil
      type and plant species. The results suggest that P. vulgaris L. mitigates Al
      stress by an internal defence mechanism and P. lunatus L. by an external one,
      both mechanisms involving organic acids. CONCLUSION: Rhizosphere mechanisms
      involved in Al detoxification were found to be different for P. vulgaris L. and
      P. lunatus L., suggesting that these processes are plant species-specific.
      Phaseolus vulgaris L. accumulates Al in the shoots (internal tolerance
      mechanism), while P. lunatus L. prevents Al uptake by releasing organic acids
      (exclusion mechanism) into the growth media.

PMID- 24037764
TI  - Spectrum of hepatic dysfunction in 2012 dengue epidemic in Kolkata, West Bengal.
AB  - Dengue fever (DF) may present as uncomplicated dengue fever, dengue hemorrhagic
      fever (DHF), or dengue shock syndrome (DSS). Transient intense viremia is
      responsible for mild, moderate, or severe hepatic dysfunction. Our aim was to
      evaluate the spectrum of hepatic dysfunction and evidence of plasma leakage in
      different stages of dengue fever in this epidemic. Detailed history, physical
      examination, and laboratory evaluation of 1,226 serologically proved dengue
      patients. Patients with DF were 170 and DHF was 1,056, among which those with ALT
      >= 75 U/L were 43 and 570, respectively. Patients with ALT > 151-300, > 300-450,
      and > 450 U/L were 186, 77, and 34, respectively. Affected DF (n = 43) and DHF (n
      = 570) patients presented with symptoms and signs similar to viral hepatitis, but
      ascites, pleural effusion, raised INR, bleeding, and hypoalbuminemia were present
      only in DHF patients. In dengue fever, there was a wide range of hepatic
      dysfunction mimicking acute viral hepatitis. 

PMID- 24037765
TI  - Odynophagia in a renal transplant recipient.

PMID- 24037766
TI  - Spontaneous cholecystocutaneous abscess.

PMID- 24037767
TI  - Zenker's diverticulum.

PMID- 24037768
TI  - Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute
      asthma.
AB  - BACKGROUND: In acute asthma inhaled beta(2)-agonists are often administered by
      nebuliser to relieve bronchospasm, but some have argued that metered-dose
      inhalers with a holding chamber (spacer) can be equally effective. Nebulisers
      require a power source and need regular maintenance, and are more expensive in
      the community setting. OBJECTIVES: To assess the effects of holding chambers
      (spacers) compared to nebulisers for the delivery of beta(2)-agonists for acute
      asthma. SEARCH METHODS: We searched the Cochrane Airways Group Trial Register and
      reference lists of articles. We contacted the authors of studies to identify
      additional trials. Date of last search: February 2013. SELECTION CRITERIA:
      Randomised trials in adults and children (from two years of age) with asthma,
      where spacer beta(2)-agonist delivery was compared with wet nebulisation. DATA
      COLLECTION AND ANALYSIS: Two review authors independently applied study inclusion
      criteria (one review author for the first version of the review), extracted the
      data and assessed risks of bias. Missing data were obtained from the authors or
      estimated. Results are reported with 95% confidence intervals (CIs). MAIN
      RESULTS: This review includes a total of 1897 children and 729 adults in 39
      trials. Thirty-three trials were conducted in the emergency room and equivalent
      community settings, and six trials were on inpatients with acute asthma (207
      children and 28 adults). The method of delivery of beta(2)-agonist did not show a
      significant difference in hospital admission rates. In adults, the risk ratio
      (RR) of admission for spacer versus nebuliser was 0.94 (95% CI 0.61 to 1.43). The
      risk ratio for children was 0.71 (95% CI 0.47 to 1.08, moderate quality
      evidence). In children, length of stay in the emergency department was
      significantly shorter when the spacer was used. The mean duration in the
      emergency department for children given nebulised treatment was 103 minutes, and
      for children given treatment via spacers 33 minutes less (95% CI -43 to -24
      minutes, moderate quality evidence). Length of stay in the emergency department
      for adults was similar for the two delivery methods. Peak flow and forced
      expiratory volume were also similar for the two delivery methods. Pulse rate was
      lower for spacer in children, mean difference -5% baseline (95% CI -8% to -2%,
      moderate quality evidence), as was the risk of developing tremor (RR 0.64; 95% CI
      0.44 to 0.95, moderate quality evidence). AUTHORS' CONCLUSIONS: Nebuliser
      delivery produced outcomes that were not significantly better than metered-dose
      inhalers delivered by spacer in adults or children, in trials where treatments
      were repeated and titrated to the response of the participant. Spacers may have
      some advantages compared to nebulisers for children with acute asthma.

PMID- 24037769
TI  - Dentistry proteomics: from laboratory development to clinical practice.
AB  - Despite all the dental information acquired over centuries and the importance of
      proteome research, the cross-link between these two areas only emerged around mid
      nineties. Proteomic tools can help dentistry in the identification of risk
      factors, early diagnosis, prevention, and systematic control that will promote
      the evolution of treatment in all dentistry specialties. This review mainly
      focuses on the evolution of dentistry in different specialties based on proteomic
      research and how these tools can improve knowledge in dentistry. The subjects
      covered are an overview of proteomics in dentistry, specific information on
      different fields in dentistry (dental structure, restorative dentistry,
      endodontics, periodontics, oral pathology, oral surgery, and orthodontics) and
      future directions. There are many new proteomic technologies that have never been
      used in dentistry studies and some dentistry areas that have never been explored
      by proteomic tools. It is expected that a greater integration of these areas will
      help to understand what is still unknown in oral health and disease.

PMID- 24037773
TI  - Motor unit potential induced repetitive discharges (MIRDs): description of an
      unusual iterative discharge.
AB  - INTRODUCTION: Repetitive discharges may be recorded during nerve conduction
      studies (NCS) or during needle electromyography in a muscle at rest. Repetitive
      discharges that occur during voluntary activation and are time-locked to
      voluntary motor unit potentials (MUP) have not been described. METHODS:
      Retrospective review of motor unit potential induced repetitive discharges
      (MIRDs) identified in the EMG laboratory. Characteristics of each MIRD, patient
      demographics, other EMG findings in the same muscle, and electrophysiological
      diagnosis were analyzed. RESULTS: MIRDs were observed in 15 patients. The
      morphology and number of spikes and duration of MIRDs varied. The discharges
      fired at rates of 50-200 Hz. All but 2 patients had EMG findings of a chronic
      neurogenic disorder. CONCLUSIONS: MIRDs are rare iterative discharges time-locked
      to a voluntary MUP. The pathophysiology of MIRDs is unclear, but their presence
      may indicate a chronic neurogenic process.

PMID- 24037774
TI  - Association of the clock genes polymorphisms with colorectal cancer
      susceptibility.
AB  - BACKGROUND AND OBJECTIVES: The circadian rhythm regulates the cell cycle
      progression and DNA damage response. The aim of our study was to investigate the
      association between polymorphisms in the CLOCK1, PER2, and PER3 genes with the
      colorectal cancer (CRC) susceptibility and clinicopathological variables.
      METHODS: Four hundred two CRC patients and 480 healthy controls were included in
      a case-control study. Genotype and allelic frequencies of 311T>C (rs1801260) in
      CLOCK1 gene, G3853A (rs934945) in PER2 gene and 4/5 repeats polymorphisms in PER3
      gene were evaluated by the polymerase chain reaction (PCR) restriction fragment
      length polymorphism method in the DNA extracted from the peripheral blood of
      patients and controls. RESULTS: The frequencies of the 311T>C CLOCK1 gene, CC
      genotype and C allele were significantly higher among CRC patients compared to
      controls (P < 0.0001) elevating the CRC risk by 2.78- and 1.78-fold respectively.
      No correlation was found between G3853A and 4/5 repeats polymorphisms and CRC
      risk. The C/G/5 and C/G/4 repeats haplotypes were higher in CRC patients (P =
      0.0009 and P = 0.038) elevating the CRC risk by 60% and 89% respectively. No
      correlation was found between any polymorphism and clinicopathological
      characteristics of CRC patients. CONCLUSION: The 311T>C polymorphism in the
      CLOCK1 gene significantly increases the risk for CRC development while it does
      not affect the outcome of CRC patients.

PMID- 24037775
TI  - Long-term results of weekly/daily cisplatin-based chemoradiation for locally
      advanced squamous cell carcinoma of the anal canal.
AB  - BACKGROUND: Weekly or daily cisplatin and 5-fluorouracil (5-FU)-based
      chemoradiation was evaluated for patients with locally advanced squamous cell
      carcinoma (SCC) of the anal canal treated at a single institution over a 20-year
      period. METHODS: A retrospective, single-institution analysis was conducted of
      patients receiving concurrent 5-FU/cisplatin and radiotherapy for locally
      advanced SCC from 1989 to 2009. Endpoints included clinical complete response
      rate, local recurrence rate, colostomy-free survival, disease-free survival
      (DFS), overall survival, and treatment-related toxicity. RESULTS: A total of 197
      patients were evaluable. The majority had American Joint Committee on Cancer
      stage II (41%) or stage III (46%) disease; most were T2 (44%) or T3 (27%); bulky
      nodal disease (N2-N3) was noted in 24% of patients. Patients received weekly (20
      mg/m2) or daily (4 mg/m2) cisplatin during radiotherapy. Median radiation dose
      was 55 Gy. Clinical complete response was observed in 185 patients (94%). After a
      median follow-up of 8.6 years, local recurrence rate was 11%. Sixteen patients
      (8%) developed distant metastases. The 5-year DFS was 81%, the 5-year overall
      survival was 86%, and the 5-year colostomy-free survival was 88%. By univariate
      analysis, N-stage was a poor prognostic indicator for 5-year DFS (P = .02, 95%
      confidence interval = 1.17-2.01) and distant metastases (P = .046, 95% confidence
      interval = 1.09-2.13). Increased T-stage correlated with the necessity for
      salvage surgery (P = .01). CONCLUSIONS: The combination of weekly/daily cisplatin
      and 5-FU-based chemotherapy with concurrent radiotherapy is an effective regimen,
      and our long-term results indicate that cisplatin is an alternative to mitomycin
      C and may be considered for the treatment of locally advanced SCC of the anal
      canal.

PMID- 24037776
TI  - Opposite effects of tamoxifen on metabolic syndrome-induced bladder and prostate
      alterations: a role for GPR30/GPER?
AB  - BACKGROUND: BPH and LUTS have been associated to obesity, hypogonadism, and
      metabolic syndrome (MetS). MetS-induced prostate and bladder alterations,
      including inflammation and tissue remodeling, have been related to a low
      testosterone and high-estrogen milieu. In addition to ERs, GPR30/GPER is able to
      mediate several estrogenic non-genomic actions. METHODS: Supplementing a subgroup
      of MetS rabbits with tamoxifen, we analyzed the in vivo effects on MetS-induced
      prostate and bladder alterations. The effects of selective ER/GPER ligands and
      GPER silencing on prostate inflammation were also studied in vitro using hBPH
      cells. RESULTS: ERalpha, ERbeta, and PR expression was upregulated in MetS
      bladder, where tamoxifen decreased ERalpha and PR expression, further stimulating
      ERbeta. In addition, tamoxifen-dosing decreased MetS-induced overexpression of
      inflammatory and tissue remodeling genes. In prostate, sex steroid receptors, pro
      inflammatory and pro-fibrotic genes were upregulated in MetS. However, tamoxifen
      did not affect them and even increased COX-2. In hBPH cells, 17beta-estradiol
      increased IL-8 secretion, an effect blunted by co-treatment with GPER antagonist
      G15 but not by ER antagonist ICI 182,780, which further increased it. GPER
      agonist G1 dose-dependently (IC50  = 1.6 nM) induced IL-8 secretion. In vitro
      analysis demonstrated that GPER silencing reverted these stimulatory effects.
      CONCLUSIONS: GPER can be considered the main mediator of estrogen action in
      prostate, whereas in bladder the mechanism appears to rely on ERalpha, as
      indicated by in vivo experiments with tamoxifen dosing. Limiting the effects of
      the MetS-induced estrogen action via GPER could offer new perspectives in the
      management of BPH/LUTS, whereas tamoxifen dosing showed potential benefits in
      bladder.

PMID- 24037777
TI  - Stem cells and aging from a quasi-immortal point of view.
AB  - Understanding aging and how it affects an organism's lifespan is a fundamental
      problem in biology. A hallmark of aging is stem cell senescence, the decline of
      functionality, and number of somatic stem cells, resulting in an impaired
      regenerative capacity and reduced tissue function. In addition, aging is
      characterized by profound remodeling of the immune system and a quantitative
      decline of adequate immune responses, a phenomenon referred to as immune
      senescence. Yet, what is causing stem cell and immune-senescence? This review
      discusses experimental studies of potentially immortal Hydra which have made
      contributions to answering this question. Hydra transcription factor FoxO has
      been shown to modulate both stem cell proliferation and innate immunity, lending
      strong support to a role of FoxO as critical rate-of-aging regulator from Hydra
      to human. Constructing a model of how FoxO responds to diverse environmental
      factors provides a framework for how stem cell factors might contribute to aging.

PMID- 24037778
TI  - A strategy to find minimal energy nanocluster structures.
AB  - An unbiased strategy to search for the global and local minimal energy structures
      of free standing nanoclusters is presented. Our objectives are twofold: to find a
      diverse set of low lying local minima, as well as the global minimum. To do so,
      we use massively the fast inertial relaxation engine algorithm as an efficient
      local minimizer. This procedure turns out to be quite efficient to reach the
      global minimum, and also most of the local minima. We test the method with the
      Lennard-Jones (LJ) potential, for which an abundant literature does exist, and
      obtain novel results, which include a new local minimum for LJ13 , 10 new local
      minima for LJ14 , and thousands of new local minima for 15<=N<=65. Insights on
      how to choose the initial configurations, analyzing the effectiveness of the
      method in reaching low-energy structures, including the global minimum, are
      developed as a function of the number of atoms of the cluster. Also, a novel
      characterization of the potential energy surface, analyzing properties of the
      local minima basins, is provided. The procedure constitutes a promising tool to
      generate a diverse set of cluster conformations, both two- and three-dimensional,
      that can be used as an input for refinement by means of ab initio methods.

PMID- 24037780
TI  - Emerging role of oxidative stress in metabolic syndrome and cardiovascular
      diseases: important role of Rac/NADPH oxidase.
AB  - 'Oxidative stress' is a term defining states of elevated reactive oxygen species
      (ROS) levels. Normally, ROS control several physiological processes, such as host
      defence, biosynthesis of hormones, fertilization and cellular signalling.
      However, oxidative stress has been involved in different pathologies, including
      metabolic syndrome and numerous cardiovascular diseases. A major source of ROS
      involved in both metabolic syndrome and cardiovascular pathophysiology is the
      NADPH oxidase (NOX) family of enzymes. NOX is a multi-component enzyme complex
      that consists of membrane-bound cytochrome b-558, which is a heterodimer of
      gp91phox and p22phox, cytosolic regulatory subunits p47phox and p67phox, and the
      small GTP-binding protein Rac1. Rac1 plays many important biological functions in
      cells, but perhaps the most unique function of Rac1 is its ability to bind and
      activate the NOX complex. Furthermore, Rac1 has been reported to be a key
      regulator of oxidative stress through its co-regulatory effects on both nitric
      oxide (NO) synthase and NOX. Therefore, the main goal of this review is to give a
      brief outline about the important role of the Rac1-NOX axis in the
      pathophysiology of both metabolic syndrome and cardiovascular disease.

PMID- 24037779
TI  - Endocrine therapy for growth retardation in paediatric inflammatory bowel
      disease.
AB  - Inflammatory bowel disease, particularly Crohn's disease (CD), can potentially
      cause growth failure during childhood as well as a reduction in final adult
      height. The underlying mechanism is multifactorial and includes poor nutrition,
      chronic inflammation, and the prolonged use of steroids. Despite major advances
      in the treatment of CD, current cohorts of children continue to display a deficit
      in linear growth and may qualify for growth-promoting hormonal therapy. However,
      currently there is limited evidence to support the use of endocrine therapy
      directed primarily at improving growth. This review is aimed at summarising the
      current evidence for growth impairment in inflammatory bowel disease and
      discusses the rationale for using growth promoting therapy. 

PMID- 24037781
TI  - Characterization of drought-tolerant sugar beet mutants induced with gamma
      radiation using biochemical analysis and isozyme variations.
AB  - BACKGROUND: In this study, drought-tolerant mutants of sugar beet (Beta vulgaris
      L. cv. Felicita) were obtained by in vitro mutagenesis and characterized by
      biochemical analysis and isozyme variations. RESULTS: Among the M1V3 plantlets,
      drought-tolerant mutants were selected on MS medium supplemented with 10-2 and
      2*10-2 kg L-1 PEG6000. As a result of biochemical analyses, drought stress
      stimulated SOD activity in eight out of ten mutants compared with the control.
      APX activity was enhanced in four out of ten mutants (M5, M8, M9 and M10),
      whereas POX and CAT activities increased significantly in all mutants.
      Additionally, FRAP values and chlorophyll (a+b, a and b) and carotenoid contents
      were enhanced under stress conditions in all mutant plants compared with the
      control. As for isozyme variations, two new POX isozyme bands (POX5 and POX1)
      were detected in all mutants but not the control, and Fe-SOD was observed in one
      out of ten mutants (M8), while the intensity of Cu/Zn-SOD was found to be
      variable in all experimental samples. Furthermore, CAT and APX isozymes were
      detected at different intensities on native gels. CONCLUSION: In vitro
      mutagenesis is a useful technique for improving plant tolerance against
      environmental stresses.

PMID- 24037782
TI  - Variability and distribution of muscle strength and its determinants in humans.
AB  - INTRODUCTION: Inter-individual variability in measurements of muscle strength and
      its determinants was identified to: (1) produce a normative data set describing
      the normal range and (2) determine whether some measurements are more informative
      than others when evaluating inter-individual differences. METHODS: Functional and
      morphological characteristics of the vastus lateralis were measured in 73
      healthy, untrained adult men. RESULTS: Inter-individual variability (coefficient
      of variation) was greater for isometric maximal voluntary contraction (MVC)
      torque (18.9%) compared with fascicle force (14.6%; P=0.025) and physiological
      cross-sectional area (PCSA; 17.2%) compared with anatomical cross-sectional area
      (ACSA, 13.0%; P<0.0005). The relationship between ACSA and isometric MVC torque
      (r(2)  =0.56) was weaker than that between PCSA and fascicle force (r(2)  =0.68).
      CONCLUSIONS: These results provide a normative data set on inter-individual
      variability in a variety of muscle strength-related measurements and illustrate
      the benefit of using more stringent measures of muscle properties. Muscle Nerve
      49: 879-886, 2014.

PMID- 24037783
TI  - A beta1/2 adrenergic receptor-sensitive intracellular signaling pathway modulates
      CCL2 production in cultured spinal astrocytes.
AB  - The phosphorylation of c-jun N-terminal kinase (JNK) and the subsequent
      production of C-C chemokine CCL2 (monocyte chemoattractant protein; MCP-1) in
      spinal astrocytes contribute to the initiation of neurological disorders
      including chronic pain. Astrocytes express neurotransmitter receptors which could
      be targeted to ameliorate neurological disorders. In the current study, the
      involvement of the beta-adrenergic system in the regulation of JNK activity and
      CCL2 production after stimulation with tumor necrosis factor (TNF)-alpha, one of
      many initiators of neuroinflammation, was elucidated. Treatment of cultured
      spinal astrocytes with isoproterenol (a beta-adrenergic receptor agonist; 1 uM)
      reduced both TNF-alpha-induced JNK1 phosphorylation, as observed by Western
      blotting, and the subsequent increase of both CCL2 mRNA expression and CCL2
      production, which were measured by real time-PCR and ELISA, respectively. The
      effects of isoproterenol were completely blocked by pretreatment with either
      propranolol (a beta-adrenoceptor antagonist) or H89 (a protein kinase A [PKA]
      inhibitor). The current study revealed that the regulation of glycogen synthase
      kinase-3beta (GSK-3beta) activity is a crucial factor in the inhibitory action of
      isoproterenol. The TNF-alpha-induced JNK1 phosphorylation was significantly
      blocked by treatment with GSK-3beta inhibitors (either LiCl or TWS119), and
      stimulation of beta-adrenergic receptors induced the inhibition of GSK-3beta
      through the phosphorylation of Ser(9) . Moreover, treatment with isoproterenol
      markedly suppressed the TNF-alpha-induced increase of CCL2 mRNA expression and
      CCL2 production through a beta-adrenergic receptor-PKA pathway mediated by GSK
      3beta regulation. Thus, activation of beta1/2 adrenergic receptors expressed in
      spinal astrocytes could be a novel method of moderating neurological disorders
      with endogenous catecholamines or selective agonists.

PMID- 24037784
TI  - Optimal timing for intravascular administration set replacement.
AB  - BACKGROUND: The tubing (administration set) attached to both venous and arterial
      catheters may contribute to bacteraemia and other infections. The rate of
      infection may be increased or decreased by routine replacement of administration
      sets. This review was originally published in 2005 and was updated in 2012.
      OBJECTIVES: The objective of this review was to identify any relationship between
      the frequency with which administration sets are replaced and rates of microbial
      colonization, infection and death. SEARCH METHODS: We searched The Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue
      6), MEDLINE (1950 to June 2012), CINAHL (1982 to June 2012), EMBASE (1980 to June
      2012), reference lists of identified trials and bibliographies of published
      reviews. The original search was performed in February 2004. We also contacted
      researchers in the field. We applied no language restriction. SELECTION CRITERIA:
      We included all randomized or controlled clinical trials on the frequency of
      venous or arterial catheter administration set replacement in hospitalized
      participants. DATA COLLECTION AND ANALYSIS: Two review authors assessed all
      potentially relevant studies. We resolved disagreements between the two review
      authors by discussion with a third review author. We collected data for seven
      outcomes: catheter-related infection; infusate-related infection; infusate
      microbial colonization; catheter microbial colonization; all-cause bloodstream
      infection; mortality; and cost. We pooled results from studies that compared
      different frequencies of administration set replacement, for instance, we pooled
      studies that compared replacement >= every 96 hours versus every 72 hours with
      studies that compared replacement >= every 48 hours versus every 24 hours. MAIN
      RESULTS: We identified 26 studies for this updated review, 10 of which we
      excluded; six did not fulfil the inclusion criteria and four did not report
      usable data. We extracted data from the remaining 18 references (16 studies) with
      5001 participants: study designs included neonate and adult populations, arterial
      and venous administration sets, parenteral nutrition, lipid emulsions and
      crystalloid infusions. Most studies were at moderate to high risk of bias or did
      not adequately describe the methods that they used to minimize bias. All included
      trials were unable to blind personnel because of the nature of the
      intervention.No evidence was found for differences in catheter-related or
      infusate-related bacteraemia or fungaemia with more frequent administration set
      replacement overall or at any time interval comparison (risk ratio (RR) 1.06, 95%
      confidence interval (CI) 0.67 to 1.69; RR 0.67, 95% CI 0.27 to 1.70). Infrequent
      administration set replacement reduced the rate of bloodstream infection (RR
      0.73, 95% CI 0.54 to 0.98). No evidence revealed differences in catheter
      colonization or infusate colonization with more frequent administration set
      replacement (RR 1.08, 95% CI 0.94 to 1.24; RR 1.15, 95% CI 0.70 to 1.86,
      respectively). Borderline evidence suggested that infrequent administration set
      replacement increased the mortality rate only within the neonatal population (RR
      1.84, 95% CI 1.00 to 3.36). No evidence revealed interactions between the (lack
      of) effects of frequency of administration set replacement and the subgroups
      analysed: parenteral nutrition and/or fat emulsions versus infusates not
      involving parenteral nutrition or fat emulsions; adult versus neonatal
      participants; and arterial versus venous catheters. AUTHORS' CONCLUSIONS: Some
      evidence indicates that administration sets that do not contain lipids, blood or
      blood products may be left in place for intervals of up to 96 hours without
      increasing the risk of infection. Other evidence suggests that mortality
      increased within the neonatal population with infrequent administration set
      replacement. However, much the evidence obtained was derived from studies of low
      to moderate quality.

PMID- 24037785
TI  - Responses of finger flexor and extensor muscles to transcranial magnetic
      stimulation during isometric force production tasks.
AB  - INTRODUCTION: In this study we investigated neural mechanisms of finger force
      control. METHODS: Ten right-handed subjects performed isometric finger flexion
      and extension force productions at 10-60% of maximum voluntary contraction (MVC)
      using 4 fingers of the dominant hand. Transcranial magnetic stimulation (TMS) was
      applied over the contralateral hand motor area. We measured fluctuation of the
      background force and TMS responses from finger flexor and extensor muscles.
      RESULTS: Force fluctuation was greater during finger extension than during finger
      flexion. Motor evoked potentials (MEPs) increased with force levels in the flexor
      digitorum superficialis (FDS) during finger flexion and in the extensor digitorum
      communis (EDC) during finger extension. TMS-induced forces increased up to 40%
      MVC and then decreased during finger flexion, whereas they decreased continuously
      through the tested force levels during finger extension. CONCLUSIONS: These
      results suggest that FDS and EDC are controlled by different neural mechanisms,
      most likely attributable to their different functional roles in daily activities.

PMID- 24037786
TI  - Projecting expenditure on medicines in the UK NHS.
AB  - BACKGROUND: Expenditure on medicines is a readily identifiable element of health
      service costs. It is the focus of much attention by payers, not least in the UK
      even though the cost of medicines represents less than 10 % of total UK National
      Health Service (NHS) expenditure. Projecting future medicines spending enables
      the likely cost pressure to be allowed for in planning the scale and allocation
      of NHS resources. Simple extrapolations of past trends in expenditure fail to
      account for changes in the rate and mix of new medicines becoming available and
      in the scope for windfall savings when some medicines lose their patent
      protection. The objective of this study is to develop and test an improved method
      to project NHS pharmaceutical expenditure in the UK for the period 2012-2015.
      METHODS: We have adopted a product-by-product, bottom-up approach, which means
      that our projections are built up from individual products to the total market.
      Our projections of the impact of generic and biosimilars entry on prices and
      quantities of medicines sold, and of the rate of uptake of newly launched
      medicines, have been obtained from regression analysis of UK data. To address
      uncertainty, we have created a baseline and two other illustrative scenarios. We
      have compared our projections with actual expenditure for 2012. RESULTS: Our
      projections estimate that, between 2011 and 2015, with no change in policy or
      price regulation, the UK total medicines bill would increase at an average
      compound annual growth rate (CAGR) of between 3.1 and 4.1 %. Total NHS spending
      on branded medicines and total NHS spending on generics are projected to increase
      at average CAGRs of 0.5-1.8 and 10.0-11.0 %, respectively, over the same time
      period. For the total market, the actual growth rate for 2012 lay within our
      projected range. CONCLUSIONS: Our methodology provides a useful framework for
      projecting UK NHS medicines expenditure over the medium term and captures the
      impacts of existing medicines losing exclusivity and of new medicines being
      launched onto the market.

PMID- 24037787
TI  - Diagnostic value of a ghrelin test for the diagnosis of GH deficiency after
      subarachnoid hemorrhage.
AB  - OBJECTIVE: To determine the diagnostic value of a ghrelin test in the diagnosis
      of GH deficiency (GHD) shortly after aneurysmal subarachnoid hemorrhage (SAH).
      DESIGN: Prospective single-center observational cohort study. METHODS: A ghrelin
      test was assessed after the acute phase of SAH and a GH-releasing hormone (GHRH)
      arginine test 6 months post SAH. Primary outcome was the diagnostic value of a
      ghrelin test compared with the GHRH-arginine test in the diagnosis of GHD. The
      secondary outcome was to assess the safety of the ghrelin test, including
      patients' comfort, adverse events, and idiosyncratic reactions. RESULTS: Forty
      three survivors of SAH were included (15 males, 35%, mean age 56. 6 +/- 11.7).
      Six out of 43 (14%) SAH survivors were diagnosed with GHD by GHRH-arginine test.
      In GHD subjects, median GH peak during ghrelin test was significantly lower than
      that of non-GHD subjects (5.4 vs 16.6, P=0.002). Receiver operating
      characteristics analysis showed an area under the curve of 0.869. A cutoff limit
      of a GH peak of 15 MUg/l corresponded with a sensitivity of 100% and a false
      positive rate of 40%. No adverse events or idiosyncratic reactions were observed
      in subjects undergoing a ghrelin test, except for one subject who reported
      flushing shortly after ghrelin infusion. CONCLUSION: Owing to its convenience,
      validity, and safety, the ghrelin test might be a valuable GH provocative test,
      especially in the early phase of SAH.

PMID- 24037789
TI  - Ca2+ clearance mechanisms in cancer cell lines and stromal cells of the prostate.
AB  - BACKGROUND: Three prostatic cell lines, PC3, LNCaP, and DU 145, are used as
      established models to study cell signaling in prostate cancer. Recently, stromal
      cell lines of the prostate, such as P21, were also introduced. Here we
      investigate a basic and important mechanism of living cells: Ca(2+) homeostasis
      in PC3, DU 145, and P21. METHODS: We examined Ca(2+) clearance mechanisms by
      monitoring the kinetics of recovery from histamine stimulation under conditions
      which inhibit prospect mechanisms for storing or extrusion of Ca(2+) from the
      cytosol by photometry. RESULTS: Despite the fact that in all three cell lines the
      Ca(2+) ATPase of the plasma membrane and the SERCA are most important for Ca(2+)
      homeostasis, inhibition of PMCA in epithelial cells has a greater effect than in
      stromal cells. Furthermore, the proportion of PMCA and SERCA differs in PC3 and
      DU145 cells. PMCA is most effective at reaching resting [Ca(2+) ]i in the final
      recovery stage. In contrast to DU 145 and P21 cells, PC3 are the only cells
      substantially affected by the inhibition of the mitochondrial uniporter. In all
      cell lines the role of the sodium calcium exchanger is marginal. CONCLUSION:
      These results demonstrate that not only cancer and stromal cell lines show
      significant differences in the modes and extent of their use of Ca(2+) clearance
      mechanisms, but also the cancer cell lines themselves.

PMID- 24037788
TI  - Integration of cancer genomics with treatment selection: from the genome to
      predictive biomarkers.
AB  - The field of cancer genomics is rapidly advancing as new technology provides
      detailed genetic and epigenetic profiling of human cancers. The amount of new
      data available describing the genetic make-up of tumors is paralleled by rapid
      advances in drug discovery and molecular therapy currently under investigation to
      treat these diseases. This review summarizes the challenges and approaches
      associated with the integration of genomic data into the development of new
      biomarkers in the management of cancer.

PMID- 24037791
TI  - An intraoperative cholangiogram: unusual anatomy.

PMID- 24037790
TI  - Protein expansion is primarily due to indels in intrinsically disordered regions.
AB  - Proteins evolve not only through point mutations but also by insertion and
      deletion events, which affect the length of the protein. It is well known that
      such indel events most frequently occur in surface-exposed loops. However,
      detailed analysis of indel events in distantly related and fast-evolving proteins
      is hampered by the difficulty involved in correctly aligning such sequences.
      Here, we circumvent this problem by first only analyzing homologous proteins
      based on length variation rather than pairwise alignments. Using this approach,
      we find a surprisingly strong relationship between difference in length and
      difference in the number of intrinsically disordered residues, where up to three
      quarters of the length variation can be explained by changes in the number of
      intrinsically disordered residues. Further, we find that disorder is common in
      both insertions and deletions. A more detailed analysis reveals that indel events
      do not induce disorder but rather that already disordered regions accrue indels,
      suggesting that there is a lowered selective pressure for indels to occur within
      intrinsically disordered regions. 

PMID- 24037792
TI  - Evidence that exercise helps in depression is still weak, finds review.

PMID- 24037793
TI  - Experts warn on data security in health and fitness apps.

PMID- 24037794
TI  - Protective effects of BML-111 against acetaminophen-induced acute liver injury in
      mice.
AB  - The present study was undertaken to investigate the effect of the new formyl
      peptide receptor 2/lipoxin A4 receptor agonist BML-111 on acetaminophen (APAP)
      induced liver injury in mice and explore its possible mechanism(s). Male Swiss
      albino mice were intraperitoneally injected with BML-111 (1 mg/kg) twice daily
      for five consecutive days prior to a single intraperitoneal injection of APAP
      (500 mg/kg). Results have shown that APAP injection caused liver damage as
      indicated by significant increase in serum alanine aminotransferase (ALT),
      aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver
      histopathological examination revealed marked necrosis and inflammation.
      Additionally, APAP decreased activities of hepatic glutathione (GSH) and
      superoxide dismutase (SOD) with significant increase in the hepatic
      malondialdehyde (MDA) content. Furthermore, APAP increased serum nitrite/nitrate
      (NO(2) (-)/NO(3) (-)) level and hepatic tumor necrosis factor alpha (TNF-alpha).
      Pretreatment with BML-111 significantly reversed all APAP-induced pathological
      changes. BML-111 prevented the increase of AST, ALT, and ALP. Also, BML-111
      markedly attenuated APAP-induced necrosis and inflammation. It decreased MDA with
      increase in SOD and GSH. Importantly, BML-111 decreased NO(2) (-)/NO(3) (-) level
      and TNF-alpha. These findings suggest that BML-111 has hepatoprotective effects
      against APAP-induced liver injury in mice. Its protective effect may be
      attributed to its ability to counteract the inflammatory ROS generation and
      regulate cytokine effects.

PMID- 24037796
TI  - Paleodemographic age-at-death distributions of two Mexican skeletal collections:
      a comparison of transition analysis and traditional aging methods.
AB  - Traditional methods of aging adult skeletons suffer from the problem of age
      mimicry of the reference collection, as described by Bocquet-Appel and Masset
      (1982). Transition analysis (Boldsen et al., 2002) is a method of aging adult
      skeletons that addresses the problem of age mimicry of the reference collection
      by allowing users to select an appropriate prior probability. In order to
      evaluate whether transition analysis results in significantly different age
      estimates for adults, the method was applied to skeletal collections from
      Postclassic Cholula and Contact-Period Xochimilco. The resulting age-at-death
      distributions were then compared with age-at-death distributions for the two
      populations constructed using traditional aging methods. Although the traditional
      aging methods result in age-at-death distributions with high young adult
      mortality and few individuals living past the age of 50, the age-at-death
      distributions constructed using transition analysis indicate that most
      individuals who lived into adulthood lived past the age of 50.

PMID- 24037795
TI  - The protective effects of 17beta-estradiol against ischemia-reperfusion injury
      and its effect on pacing postconditioning protection to the heart.
AB  - The role of pacing postconditioning (PPC) in the heart protection against
      ischemia-reperfusion injury is not completely understood. The aim of this study
      was to investigated if 17-beta-estradiol (estrogen, E2), endogenous atrial
      natriuretic peptide (ANP), endogenous brain natriuretic peptide (BNP), and tumor
      necrosis factor-alpha (TNF-alpha) are involved in PPC-mediated protection.
      Langendorff perfused female Wistar rat hearts were used for this study. Hearts
      challenged with regional ischemia for 30 min subjected to no further treatment
      served as a control. The PPC protocol was 3 cycles of 30 s pacing alternated
      between the right atrium and left ventricle (LV). Protection was assessed by
      recovery of LV contractility and coronary vascular-hemodynamics. Ischemia induced
      a significant (P < 0.05) deterioration in the heart function compared with
      baseline data. PPC alone or in combination with short-term E2 treatment (E2
      infusion at the beginning of reperfusion) significantly (P < 0.05) improved the
      heart functions. Short-term E2 treatment post-ischemically afforded protection
      similar to that of PPC. However, long-term E2 substitution for 6 weeks completely
      attenuated the protective effects of PPC. Although no changes were noted in
      endogenous ANP levels, PPC significantly increased BNP expression level and
      decreased TNF-alpha in the cardiomyocyte lysate and coronary effluent compared to
      ischemia and controls. Our data suggested a protective role for short-term E2
      treatment similar to that of PPC mediated by a pathway recruiting BNP and
      downregulating TNF-alpha. Our study further suggested a bad influence for long
      term E2 substitution on the heart as it completely abrogated the protective
      effects of PPC.

PMID- 24037797
TI  - How do experts define relevance criteria when initiating Health Impact
      Assessments of national policies?
AB  - AIM: The aim of this article is to present how the Danish Disease Prevention
      Committee (DDPC) members and HIA-experts understand when HIA is "relevant", which
      in this context means when there is "presumed to be a direct and documented
      effect on the health and morbidity of citizens". METHOD: DDPC members were
      interviewed face-to-face; HIA experts participated in an e-survey. RESULTS: Six
      DDPC members were interviewed and 100 HIA-experts participated in a survey. The
      DDPC members consider direct as the link between determinants and the related
      risk factors. The HIA experts consider direct as the link between policy and the
      related risk factors. Both groups favour the use of scientific evidence according
      to the traditional biomedical evidence hierarchy but HIA-experts also judge that
      there is value in using evidence that can be considered weak such as local
      community knowledge. CONCLUSIONS: It is clear that the DDPC recommendation gives
      rise to a discussion on differing perceptions of relevance. The same definition
      can be used for both direct and indirect effects depending on interpretation.
      Documented evidence for an effect is desirable in the form provided by the
      traditional biomedical evidence hierarchy but HIA-experts emphasises use of local
      knowledge. The primary criteria for initiating a HIA, is whether the outcome of
      the HIA is expected to be taken into account in the decision-making process. The
      second criteria, is how do decision-makers perceive or interpret a decision to be
      relevant for HIA. This has implications for how and whether HIA will be
      implemented in Denmark in the future.

PMID- 24037798
TI  - A prospective cohort study of quality of life and ischemic heart disease.
AB  - AIMS: To examine the role of self-rated quality of life, as a whole, on the risk
      of developing ischemic heart disease. METHODS: Information on self-rated quality
      of life and covariates was obtained from 4497 people from the Copenhagen
      Perinatal Cohort. The study population, consisting of both men and women aged 31
      33 years at baseline, was followed for registration of ischemic heart disease in
      national registers. Two different follow-up periods were examined. RESULTS: Using
      a follow-up of 13 years, the basis-adjusted hazard ratio among women who rated
      their quality of life as poor was 2.93 (95% CI: 1.09-7.86), compared with women
      who rated their quality of life as very good. The hazard ratio of women who rated
      their quality of life as good, compared to very good, was 2.99 (95% CI: 1.22
      7.29). When analyzing 16 years of follow-up, estimates among women were lower and
      some of the hazard ratios were insignificant. All hazard ratios among men were
      below two and none were statistically significant. CONCLUSIONS: Among women, the
      risk for ischemic heart disease was two to four times greater for those who rated
      their quality of life as poor or good, than for women with the most positive
      rating. For men, the association was not statistically significant.

PMID- 24037799
TI  - Chemically intuitive indices for charge-transfer excitation based on SAC-CI and
      TD-DFT calculations.
AB  - A recently proposed charge-transfer (CT) index and some related quantities aimed
      to the description of CT excitations in push-pull donor-acceptor model systems
      were computed in vacuum and in ethanol by the direct symmetry-adapted cluster
      configuration interaction (SAC-CI) method including solvent effects by means of
      the nonequilibrium state-specific approach. The effects of both solvation and
      electron correlations on these quantities were found to be significant. The
      present results are also in line with previous time-dependent (TD) density
      functional theory calculations and they demonstrate that SAC-CI provides a
      description of the excitation character close to that of TD-PBE0. Indeed, CT
      indices evaluated by the SAC-CI and TD-PBE0 would be useful in the field of
      materials chemistry, for the design and development of novel molecular materials.

PMID- 24037800
TI  - Health risk assessment of cadmium via dietary intake by adults in China.
AB  - BACKGROUND: Cadmium in the human diet constitutes a potential chronic hazard to
      health. The objective of this study was to make a health risk assessment of
      dietary cadmium intake by adults in the 31 provinces (excluding Hong Kong, Taiwan
      and Macau) of China. RESULTS: The cadmium levels in a total of 2629 individual
      food samples ranged from not detected (below the limit of detection) to 17.32 mg
      kg-1, with the highest concentration being found in an offal sample. The food
      group 'meat' showed the highest mean level of 0.129 mg kg-1, while the lowest
      concentration of 8.0*10-4 mg kg-1 was measured in the food group 'fruit'. The
      mean cadmium intakes, hazard quotients and annual excess lifetime cancer risks
      for national, northern and southern adult populations in China were 3.67 MUg kg-1
      body weight (BW) week-1, 0.52 and 4.56*10-5 a-1, 2.63 MUg kg-1 BW week-1, 0.38
      and 3.27*10-5 a-1 and 4.56 MUg kg-1 BW week-1, 0.65 and 5.67*10-5 a-1
      respectively. CONCLUSION: The results of risk characterization for the national
      adult population were lower than safety risk levels of hazard quotient and annual
      excess lifetime cancer risk (5*10-5 a-1). The mean annual excess lifetime cancer
      risk for the southern adult population was higher than the safety risk level.
      Therefore the carcinogenic risk for the southern population is of concern.

PMID- 24037801
TI  - Preservation of neurocognitive function and local control of 1 to 3 brain
      metastases treated with surgery and carmustine wafers.
AB  - BACKGROUND: Neurosurgical resection and whole-brain radiation therapy (WBRT) are
      accepted treatments for single and oligometastatic cancer to the brain. To avoid
      the decline in neurocognitive function (NCF) linked to WBRT, the authors
      conducted a prospective, multicenter, phase 2 study to determine whether surgery
      and carmustine wafers (CW), while deferring WBRT, could preserve NCF and achieve
      local control (LC). METHODS: NCF and LC were measured in 59 patients who
      underwent resection and received CW for a single (83%) or dominant
      (oligometastatic, 2 to 3 lesions) metastasis and received stereotactic
      radiosurgery (SRS) for tiny nodules not treated with resection plus CW.
      Preservation of NCF was defined as an improvement or a decline <= 1 standard
      deviation from baseline in 3 domains: memory, executive function, and fine motor
      skills, evaluated at 2-month intervals. RESULTS: Significant improvements in
      executive function and memory occurred throughout the 1-year follow-up.
      Preservation or improvement of NCF occurred in all 3 domains for the majority of
      patients at each of the 2-month intervals. NCF declined in only 1 patient. The
      chemowafers were well tolerated, and serious adverse events were reversible.
      There was local recurrence in 28% of the patients at 1-year follow-up.
      CONCLUSIONS: Patients with brain metastases had improvements in their cognitive
      trajectory, especially memory and executive function, after treatment with
      resection plus CW. The rate of LC (78%) was comparable to historic rates of
      surgery with WBRT and superior to reports of WBRT alone. For patients who undergo
      resection for symptomatic or large-volume metastasis or for tissue diagnosis, the
      addition of CW can be considered as an option.

PMID- 24037802
TI  - Sex differences in time to task failure during early pubertal development.
AB  - INTRODUCTION: We compared fatigability and activation of elbow flexor muscles in
      children at 3 pubertal stages during a sustained submaximal contraction. METHODS:
      In 72 healthy children (39 boys) aged 11 +/- 3 years (range, 8-14 years),
      differences in fatigability (time to task failure) and muscle activation were
      compared at 3 Tanner stages (T1-T3). RESULTS: Time to task failure and muscle
      activation were similar between boys and girls at prepubertal Tanner stage 1.
      Time to task failure was briefer for girls than boys at Tanner stages 2 and 3 and
      was predicted by the coactivation indices and percent body fat in girls. Muscle
      torque was the only predictor for the time to task failure in boys. CONCLUSIONS:
      Differences in fatigability and muscle coactivation were evident during the
      initial pubertal stages (T2 and T3), but not before the onset of puberty (T1).

PMID- 24037803
TI  - P2X7 receptors in neurohypophysial terminals: evidence for their role in arginine
      vasopressin secretion.
AB  - Arginine-vasopressin (AVP) plays a major role in maintaining cardiovascular
      function and related pathologies. The mechanism involved in its release into the
      circulation is complex and highly regulated. Recent work has implicated the
      purinergic receptor, P2X7R, in a role for catecholamine-enhanced AVP release in
      the rat hypothalamic-neurohypophysial (NH) system. However, the site of P2X7R
      action in this endocrine system, and whether or not it directly mediates release
      in secretory neurons have not been determined. We hypothesized that the P2X7R is
      expressed and mediates AVP release in NH terminals. P2X7R function was first
      examined by patch-clamp recordings in isolated NH terminals. Results revealed
      that subpopulations of isolated terminals displayed either high ATP-sensitivity
      or low ATP-sensitivity, the latter of which was characteristic of the rat P2X7R.
      Additional recordings showed that terminals showing sensitivity to the P2X7R
      selective agonist, BzATP, were further inhibited by P2X7R selective antagonists,
      AZ10606120 and brilliant blue-G. In confocal micrographs from tissue sections and
      isolated terminals of the NH P2X7R-immunoreactivity was found to be localized in
      plasma membranes. Lastly, the role of P2X7R on AVP release was tested. Our
      results showed that BzATP evoked sustained AVP release in NH terminals, which was
      inhibited by AZ10606120. Taken together, our data lead us to conclude that the
      P2X7R is expressed in NH terminals and corroborates its role in AVP secretion.

PMID- 24037804
TI  - Body image and breastfeeding practices in obese mothers.
AB  - PURPOSE: This study analyzed body image perceptions and breastfeeding practices
      in obese mothers. METHODS: Prospective, case-control study on 25 obese (BMI >30
      kg/m(2)) and 25 normal-weight puerperae, matched for parity and delivery route.
      The participants completed the Body Uneasiness Test, a two-part, self-report
      questionnaire, investigating body image perception before they were discharged
      from hospital and participated in telephone interviews concerning breastfeeding
      practices. RESULTS: Obese women demonstrated body image dissatisfaction related
      to their obesity. On average, they reported significantly higher scores on Global
      Severity Index (p < 0.0001) and on all of the BUT-A subscales: Weight Phobia (p <
      0.02), Body Image Concerns (p < 0.0001), Avoidance (p < 0.0001), Compulsive Self
      Monitoring (p < 0.01), and Depersonalization (p = 0.002) than did normal-weight
      puerperae. Moreover, they also had higher BUT-B scores and the Positive Symptom
      Total was significantly higher (p < 0.002). Finally, while breastfeeding
      practices at discharge were similar in the two groups, the obese mothers were
      more likely to maintain full breastfeeding at 6 months (p < 0.04). CONCLUSIONS:
      Obese mothers have negative body image perceptions but they maintain full
      breastfeeding longer.

PMID- 24037805
TI  - Pathology is a necessary and informative tool in oncology clinical trials.
AB  - Clinical trials are essential for the improvement of cancer care. The complexity
      of modern cancer care and research require careful design, for which input from
      all disciplines is necessary. Pathologists should play a key role in the design
      and execution of modern cancer trials, with special attention to the eligibility,
      stratification and evaluation of response to therapy. In the current review all
      these aspects are discussed, with examples from colorectal cancer trials. We
      describe critical issues in biomarker evaluation and development and emphasize
      the importance of the role of the pathologist in quality control of cancer
      treatment.

PMID- 24037806
TI  - Simultaneous determination of six C21 steroids of Xiao-Ai-Ping injection in rat
      plasma by LC-MS/MS.
AB  - Xiao-Ai-Ping injection (XAPI) is a traditional Chinese medicine that has been
      widely used to treat cancer. Modern pharmacological studies have demonstrated
      that C21 steroids are the main active compounds in XAPI. In this study, a
      sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS)
      method was developed and validated the first time for simultanenous determination
      of three isomeric pregnane genins (17beta-tenacigenin B, tenacigenin B and
      tenacigenin A) and their corresponding glycosides (tenacigenoside A,
      tenacissoside F and marsdenoside I) from XAPI in rat plasma. A simple liquid
      liquid extraction technique was used after the addition of dexamethasone acetate
      as internal standard. The chromatography separation of analytes was achieved on
      an Agilent Zorbax Eclipse XDB-C18 column (3.5 um, 150 * 3 mm i.d.) using methanol
      water as mobile phase in a gradient elution program. Detection was performed in
      multiple reaction monitoring mode using electrospray ionization in the negative
      ion mode. The method showed satisfactory linearity over a concentration range
      5.00-2000.00 ng/mL for tenacigenin B, tenacigenin A, marsdenoside I and
      tenacissoside F (r(2) > 0.99), 10.00-4000.00 ng/mL for 17beta-tenacigenin B and
      tenacigenoside A (r(2) > 0.99). Intra- and inter-day precisions (valued as
      relative standard deviation) were <9.00% and accuracies (as relative error) in
      the range -6.31 to 7.23%. Finally, this validated method was successfully applied
      to the pharmacokinetic study of XAPI after intravenous administration to rats.

PMID- 24037807
TI  - Spatial distribution of motor units recruited during electrical stimulation of
      the quadriceps muscle versus the femoral nerve.
AB  - INTRODUCTION: In this study we investigated differences in the spatial
      recruitment of motor units (MUs) in the quadriceps when electrical stimulation is
      applied over the quadriceps belly versus the femoral nerve. METHODS: M-waves and
      mechanical twitches were evoked using over-the-quadriceps and femoral nerve
      stimulation of gradually increasing intensity from 22 young, healthy subjects.
      Spatial recruitment was investigated using recruitment curves of M-waves recorded
      from the vastus medialis (VM) and vastus lateralis (VL) and of twitches recorded
      from the quadriceps. RESULTS: At maximal stimulation intensity (Imax), no
      differences were found between nerve and over-the-quadriceps stimulation. At
      submaximal intensities, VL M-wave amplitude was higher for over-the-quadriceps
      stimulation at 40% Imax, and peak twitch force was greater for nerve stimulation
      at 60% and 80% Imax. CONCLUSIONS: For the VM, MU spatial recruitment during nerve
      and over-the-quadriceps stimulation of increasing intensity occurred in a similar
      manner, whereas significant differences were observed for the VL.

PMID- 24037808
TI  - Cardiovascular magnetic resonance imaging predictors of pregnancy outcomes in
      women with coarctation of the aorta.
AB  - AIMS: The aim of this study was to determine associations between aortic
      morphometry evaluated by cardiovascular magnetic resonance (CMR) and pregnancy
      outcomes in women with aortic coarctation (CoA). METHODS: Consecutive women with
      CoA seen with CMR within 2 years of delivery were reviewed. Aortic dimensions
      were measured on CMR angiography. Adverse outcomes (cardiovascular, obstetric,
      and foetal/neonatal) were documented. RESULTS: We identified 28 women (4 with
      native and 24 with repaired CoA) who had 30 pregnancies. There were 29 live
      births (1 stillbirth) at mean gestation 38 +/- 2 weeks. Mean maternal ages at
      first cardiac intervention and pregnancy were 6 +/- 8 and 29 +/- 6 years,
      respectively. There were nine cardiovascular events (hypertensive complications
      in five; stroke in two and arrhythmia in two) occurring in seven pregnancies.
      Minimum aortic dimensions were smaller in women with cardiovascular events (12.1
      vs. 14.3 mm, P = 0.001), specifically in those with hypertensive complications
      (11.6 vs. 14.4 mm, P < 0.001). From receiver operator curve analysis, optimal
      discrimination for the development of adverse cardiovascular events occurred at
      the 12 mm diameter threshold [sensitivity 78%, specificity 91%, area under the
      curve 0.86 (95% CI: 0.685-1)]. All hypertensive events occurred in conjunction
      with a minimum aortic diameter of 12 mm (7mm/m(2)) or less. No adverse outcomes
      occurred if minimum diameter exceeded 15 mm. CONCLUSION: Smaller aortic
      dimensions relate to increased risk of hypertensive events in pregnant women with
      CoA. CMR can aid in stratification of risk for women with CoA who are considering
      pregnancy.

PMID- 24037810
TI  - Splitting multiple bonds: a comparison of methodologies on the accuracy of bond
      dissociation energies.
AB  - A benchmarking of different quantum chemical methodologies for the splitting of
      multiply bonded systems is presented, with an emphasis on quantitative
      reproduction of experimentally determined dissociation energies. New benchmark
      full configuration interaction (FCI) calculations are presented for nitrogen and
      acetylene, and comparisons are made between various methods with both the FCI
      results and with experiment in an effort to understand qualitatively and
      quantitatively how well these different methods cope with the bond-breaking
      process. It is found that the multireference methods fare well, but are sometimes
      slowly convergent with respect to the size of the basis set, and in particular
      the angular momenta of the polarization functions. Single-reference (SR)
      wavefunction-based methods perform poorly against full CI, while CCSD(T) is
      reasonably accurate for comparison with experiment. Density functional theory
      with hybrid functionals have very quick basis-set convergence, and offer reliable
      estimates of bond dissociation energies. Spin-restricted SR wavefunctions are
      found to be poor for such systems, while unrestricted wavefunctions give
      reasonably good energies, but with severe spin contamination.

PMID- 24037809
TI  - An unusual case of bilateral multifocal retinal pigment epithelial detachment
      with methanol-induced optic neuritis.
AB  - PURPOSE: To describe an unusual case of methanol-induced optic neuritis with
      bilateral multifocal extrafoveal serous retinal pigment epithelial (RPE)
      detachment. METHODS: Single case report. CASE REPORT: A 40-year-old male
      presented with acute bilateral loss of vision and history of consumption of
      adulterated alcohol. On examination, his vision was perception of light in the
      right eye and finger counting at 1-ft distance in the left eye. Pupillary
      reactions were sluggish. The optic discs were normal. An elevated lesion with
      subretinal serous fluid was present over macula adjacent to superior major vessel
      arcade in the right eye, which was confirmed as a large extrafoveal RPE
      detachment on fluorescein angiography. There were two more small RPE detachments
      in the right eye as well as in the left eye. All RPE detachments were extrafoveal
      in location. The patient was managed medically with intravenous
      methylprednisolone (1 g) in 500 ml of ringer lactate for three consecutive days.
      After three doses, visual acuity of both eyes was recorded as 20/20. CONCLUSION:
      We herein report an unusual case of bilateral multifocal extrafoveal serous RPE
      detachment in a patient of methanol-induced optic neuritis. RPE detachments may
      be due to the toxic effect of methanol metabolites.

PMID- 24037811
TI  - Determinants of health-promoting lifestyle behaviors among Arab immigrants from
      the region of the Levant.
AB  - Arab immigrants in the United States are at risk for heart disease, stroke, and
      diabetes. We explored health-promoting lifestyle behaviors among Arab immigrants
      to the United States from the Middle Eastern region of the Levant. In 218 male
      and female Arab adults surveyed with the revised Health-Promoting Lifestyle
      Profile (HPLP-II), the mean for the HPLP-II was 2.73 (range 1-4), with spiritual
      growth and interpersonal relations the most frequently reported practices and
      physical activity the least frequently practiced dimension of health-promoting
      behaviors. Multiple linear regression analysis highlighted four determinants of
      health-promoting lifestyle behaviors: health insurance, acculturation, self
      efficacy, and social support. Health promotion programs serving Arab immigrants
      should take these determinants into consideration.

PMID- 24037812
TI  - Mammographic screening interval in relation to tumor characteristics and false
      positive risk by race/ethnicity and age.
AB  - BACKGROUND: Biennial screening mammography retains most of the benefits of annual
      breast cancer screening with reduced harms. Whether screening guidelines based on
      race/ethnicity and age would be more effective than age-based guidelines is
      unknown. METHODS: Mammography data from the Breast Cancer Surveillance Consortium
      were linked to pathology and tumor databases. The authors identified women aged
      40 to 74 years who underwent annual, biennial, or triennial screening mammography
      between 1994 and 2008. Logistic regression was used to estimate adjusted odds
      ratios (OR) and 95% confidence intervals (95% CI) of adverse tumor
      characteristics among 14,396 incident breast cancer cases and 10-year cumulative
      risks of false-positive recall and biopsy recommendation among 1,276,312
      noncases. RESULTS: No increased risk of adverse tumor characteristics associated
      with biennial versus annual screening were noted in white women, black women,
      Hispanic women aged 40 to 49 years, or Asian women aged 50 to 74 years. Hispanic
      women aged 50 to 74 years who screened biennially versus annually were found to
      have an increased risk of late-stage disease (OR, 1.6; 95% CI, 1.0-2.5) and large
      tumors (OR, 1.6; 95% CI, 1.1-2.4). Asian women aged 40 to 49 years who underwent
      biennial screening had an elevated risk of positive lymph nodes (OR, 3.1; 95% CI,
      1.3-7.1). No elevated risks were associated with triennial versus biennial
      screening. Cumulative false-positive risks decreased markedly with a longer
      screening interval. CONCLUSIONS: The authors found limited evidence of elevated
      risks of adverse tumor characteristics with biennial versus annual screening,
      whereas cumulative false-positive risks were lower. However, elevated risks of
      late-stage disease in Hispanic women and lymph node-positive disease in younger
      Asian women who screened less often than annually warrant consideration and
      replication.

PMID- 24037813
TI  - Effect of prebiotic carbohydrates on growth, bile survival and cholesterol uptake
      abilities of dairy-related bacteria.
AB  - BACKGROUND: Three strains of lactic acid bacteria and one probiotic
      Bifidobacterium strain sourced from milk origin were considered to select for the
      best synbiotic-like combination for cholesterol uptake ability. For that purpose,
      fermentative characteristics, bile salt hydrolase activity, bile survival and
      cholesterol removal were assessed in the presence of different carbohydrates.
      RESULTS: Carbohydrate fermentability was highly variable among the different
      strains, and lactulose was the only prebiotic to favour growth of all strains,
      whereas pectin led to low population regardless of the strain. Bile survival of
      bacteria could be improved by the preferred carbon source and was related to
      their bile salt hydrolase activities. All together, our results showed that the
      most advantageous synbiotic-like combinations to achieve cholesterol uptake
      abilities were Lactobacillus delbrueckii subsp. bulgaricus LB 340 with raffinose,
      Streptococcus thermophilus TA040 or Lactobacillus rhamnosus LBRE-LSAS with
      lactulose, and Bifidobacterium animalis subsp. lactis Bb12 with mannitol.
      CONCLUSION: The suggested synbiotics may represent new promising functional dairy
      additives.

PMID- 24037814
TI  - Seroprevalence and risk factors of Crimean-Congo hemorrhagic fever in selected
      seven provinces in Turkey.
AB  - Turkey has been one of the most endemic regions since 2002, when Crimean-Congo
      hemorrhagic fever emerged worldwide. The aim of the present study was to estimate
      the seroprevelance of CCHF virus in humans who reside in rural and urban areas of
      known endemic and nonendemic selected provinces of Turkey by using commercial
      ELISA kit. CCHFV IgG antibodies were detected in 2.3% of the population. The most
      important risk factors for CCHF seropositivity, were older age, male gender,
      illiterate, farmer, animal husbandry, living in rural residence in adobe houses,
      and a previous tick bite history.

PMID- 24037815
TI  - Effects of organic modifier and temperature on the enantiomeric separation of
      several azole drugs using supercritical fluid chromatography and the Chiralpak AD
      column.
AB  - The effects of organic modifier and temperature on the enantioseparation of 10
      triazoles and eight imidazoles, using supercritical fluid chromatography with the
      Chiralpak AD column, have been investigated in this work. For this purpose four
      different organic modifiers (methanol, ethanol, 2-propanol and acetonitrile) were
      evaluated. Only in the case of two compounds could the enantiomeric separation
      not be achieved with any of the modifiers tested; the rest of compounds were
      baseline or partially resolved with at least one of the modifiers. The alcohol
      type modifiers provided the best results in terms of retention time and
      resolution. In general, retention increased in the order methanol < ethanol < 2
      propanol; moreover it was possible to establish a relationship between the
      retention and the number of aromatic rings and dioxolane groups in the molecule,
      that is, the higher the number is, the higher the retention time. From the study
      of the temperature effect, the enthalpy-entropy compensation was demonstrated for
      all the compounds, except for bifonazole using methanol and miconazole using
      acetonitrile. This suggested that both analytes are enantiomerically resolved
      through different mechanisms.

PMID- 24037817
TI  - Leon Morgenstern: a tribute.

PMID- 24037816
TI  - Nitric oxide regulation of Na, K-ATPase activity in ocular ciliary epithelium
      involves Src family kinase.
AB  - The nitric oxide (NO) donor sodium nitroprusside (SNP) is known to reduce aqueous
      humor (AH) secretion in the isolated porcine eye. Previously, SNP was found to
      inhibit Na,K-ATPase activity in nonpigmented ciliary epithelium (NPE), AH
      secreting cells, through a cGMP/protein kinase G (PKG)-mediated pathway. Here we
      show Src family kinase (SFK) activation in the Na,K-ATPase activity response to
      SNP. Ouabain-sensitive (86) Rb uptake was reduced by >35% in cultured NPE cells
      exposed to SNP (100 uM) or exogenously added cGMP (8-Br-cGMP) (100 uM) and the
      SFK inhibitor PP2 (10 uM) prevented the response. Ouabain-sensitive ATP
      hydrolysis was reduced by ~40% in samples detected in material obtained from SNP-
      and 8-Br-cGMP-treated cells following homogenization, pointing to an intrinsic
      change of Na,K-ATPase activity. Tyrosine-10 phosphorylation of Na,K-ATPase alpha1
      subunit was detected in SNP and L-arginine-treated cells and the response
      prevented by PP2. SNP elicited an increase in cell cGMP. Cells exposed to 8-Br
      cGMP displayed SFK activation (phosphorylation) and inhibition of both ouabain
      sensitive (86) Rb uptake and Na,K-ATPase activity that was prevented by PP2. SFK
      activation, which also occurred in SNP-treated cells, was suppressed by
      inhibitors of soluble guanylate cyclase (ODQ; 10 uM) and PKG (KT5823; 1 uM). SNP
      and 8-Br-cGMP also increased phosphorylation of ERK1/2 and p38 MAPK and the
      response prevented by PP2. However, U0126 did not prevent SNP or 8-Br-cGMP
      induced inhibition of Na,K-ATPase activity. Taken together, the results suggest
      that NO activates guanylate cyclase to cause a rise in cGMP and subsequent PKG
      dependent SFK activation. Inhibition of Na,K-ATPase activity depends on SFK
      activation.

PMID- 24037820
TI  - Frequency and spectrum of myopathies in patients with psoriasis.
AB  - INTRODUCTION: Psoriasis is a T-cell-mediated skin disorder with uncommon
      extracutaneous manifestations. Rare patients with psoriasis and myopathy have
      been reported. METHODS: We conducted a retrospective review of medical records of
      psoriasis patients seen at the Mayo Clinic during the period from January 1, 1996
      to May 31, 2011. Patients who had pathologically confirmed myopathy or
      lymphocytic infiltrates in muscle were included. RESULTS: Among 11,370 psoriasis
      patients, 13 had pathologically confirmed myopathies. Seventy percent were
      inflammatory myopathies, and 2 had focal inflammation in the muscle. Psoriasis
      preceded myopathy onset in two-thirds of the patients (median 14.7 years). Half
      of the patients had psoriatic arthritis; 60% had other autoimmune disorders.
      Patients who received anti-tumor necrosis factor-alpha (anti-TNF-alpha) therapy
      had a higher risk for developing myopathy or inflammation in muscle (odds ratio =
      4.45). CONCLUSIONS: Myopathy or inflammation in muscle affects an average of 1.32
      of every 1000 psoriasis patients. Concomitant autoimmune disorders, psoriatic
      arthritis, and exposure to anti-TNF-alpha therapy may be associated with
      increased risk of developing myopathy in psoriasis patients.

PMID- 24037821
TI  - Glomerular filtration rate equations for liver-kidney transplantation in patients
      with cirrhosis: validation of current recommendations.
AB  - Simultaneous liver and kidney transplantation (SLKT) remains the procedure of
      choice for patients with both endstage liver disease and kidney failure.
      Stringent guidelines are needed to avoid unnecessary kidney transplantation. A
      recent consensus meeting proposed criteria based on the Modified Diet in Renal
      Disease (MDRD)-6 equation to estimate glomerular filtration rate (GFR). The aims
      of this study were to compare GFR equations to true GFR in candidates for liver
      transplantation (LT) and to determine the impact of inaccuracies on the current
      guidelines for SLKT. Three hundred stable cirrhosis patients evaluated for LT
      were studied. All patients had iohexol clearance to measure GFR at evaluation
      under stable conditions. Measured GFR (mGFR) was compared to MDRD-4, MDRD-6, and
      Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. MDRD-6 was
      the most accurate equation to predict GFR. In the 290 patients with mGFR >30
      mL/min/1.73 m(2), 15 patients (7%) had estimated GFR (eGFR) <=40 mL/min/1.73 m(2)
      based on the MDRD-6 equation, defining "discordant" patients. Among them, two
      underwent SLKT and 13 underwent LT alone. None of those who survived more than 1
      year after LT alone (n = 8) developed renal dysfunction thereafter. In
      multivariate analysis, discordant patients were older (P = 0.03) and had lower
      sodium level (P = 0.02). CONCLUSION: The MDRD-6 equation was superior to other
      equations at identifying cirrhosis patients with true GFR <30 mL/min/1.73 m(2).
      However, the MDRD-6 equation also tended to underestimate renal function in a
      subgroup of patients with true GFR >30 mL/min/1.73 m(2), with a potential risk of
      unnecessary kidney transplantation if applying current U.S. recommendations for
      SLKT.

PMID- 24037822
TI  - Detecting field cancerization using a hyperspectral imaging system.
AB  - BACKGROUND: Field cancerization denotes subclinical abnormalities in a tissue
      chronically exposed to UV radiation. These abnormalities can be found surrounding
      the clinically visible actinic keratoses. OBJECTIVES: The aim of this study was
      to test the feasibility of a hyperspectral imaging system in the detection of
      multiple clinical and subclinical AKs for early treatment of the affected areas.
      MATERIALS AND METHODS: Altogether 52 clinical AKs in 12 patients were included in
      this study. In six patients digital photos were taken of the naive AKs, and again
      after methylaminolevulinate(MAL)-fluorescence diagnosis which was used to teach
      HIS to find subclinical lesions. After 2-3 days when the MAL had vanished, the
      hyperspectral images were taken. Biopsies were taken from clinical AKs, healthy
      looking skin and several suspected subclinical AKs. In the other six patients
      digital and hyperspectral images were taken of the naive AKs followed by one
      biopsy per patient. RESULTS: HIS detected all clinically visible 52 AKs and
      numerous subclinical lesions. The histopathology of the 33 biopsied lesions were
      concordant with the HIS results showing either AK (n = 28) or photodamage (n =
      5). Of the 28 histopathologically confirmed AKs, 16 were subclinical. A specific
      diffuse reflectance spectrum of an AK and healthy skin was defined. CONCLUSION:
      The hyperspectral imaging system offers a new, non-invasive method for early
      detection of field cancerization. Lasers Surg. Med. 45:410-417, 2013. (c) 2013
      Wiley Periodicals, Inc.

PMID- 24037823
TI  - Photocoagulation in rabbits: optical coherence tomographic lesion classification,
      wound healing reaction, and retinal temperatures.
AB  - BACKGROUND AND OBJECTIVE: The rabbit is the most common animal model to study
      retinal photocoagulation lesions. We present a classification of retinal lesions
      from rabbits, that is based on optical coherence tomographic (OCT) findings,
      temperature data, and OCT-follow-up data over 3 months. MATERIALS AND METHODS:
      Four hundred eighty-six photocoagulation lesions (modified Zeiss Visulas(r) 532
      nm CW laser, lesion diameter 133 um, exposure duration 200  milliseconds or
      variable, power variable) were analyzed from six eyes of three chinchilla gray
      rabbits. During the irradiation of each lesion, we used an optoacoustics-based
      method to measure the retinal temperature profile. Two hours, 1 week, 1 month,
      and 3 months after the treatment, we obtained fundus color and OCT
      (Spectralis(r)) images of each lesion. We classified the lesions according to
      their OCT morphology and correlated the findings to ophthalmoscopic and OCT
      lesion diameters, and temperatures. RESULTS: Besides an undetectable lesion class
      0, we discerned subthreshold lesions that were invisible on the fundus but
      detectable in OCT (classes 1 and 2), very mild lesions that were partly visible
      on the fundus (class 3), and 3 classes of suprathreshold lesions. OCT greatest
      linear diameters (GLDs) were larger than ophthalmoscopic lesion diameters, both
      increased for increasing classes, and GLDs decreased over 3 months within each
      class. Mean peak end temperatures for 200  milliseconds lesions ranged from 61
      degrees C in class 2 to 80 degrees C in class 6. CONCLUSION: The seven step
      rabbit lesion classifier is distinct from a previously published human lesion
      classifier. Threshold lesions are generated at comparable temperatures in rabbits
      and humans, while more intense lesions are created at lower temperatures in
      rabbits. The OCT lesion classifier could replace routine histology in some
      studies, and the presented data may be used to estimate lesion end temperatures
      from OCT images.

PMID- 24037824
TI  - Modulation of PPIX synthesis and accumulation in various normal and glioma cell
      lines by modification of the cellular signaling and temperature.
AB  - Effective therapies for malignant gliomas are still elusive and limited survival
      improvements are provided only by Temozolomide or fluorescence guided resection.
      The efficacy of photodynamic therapy (PDT) in this indication is limited by the
      higher sensitivity of normal brain structures compared to glioma necessitating a
      modulation of its sensitivity. We evaluate the influence of hypothermia and the
      tyrosine kinase inhibitor Erlotinib on cell's ability to synthesize PPIX
      following the administration of ALA which was not previously investigated. We
      demonstrate that both hypothermia and Erlotinib are favorable in PPIX selectivity
      as only glioma cell lines demonstrate an increased PPIX synthesis, whereas the
      neuronal and astrocytic synthesis is remaining unaffected. The results are
      encouraging to consider hypothermia and Erlotinib as adjuvant therapies to
      increase the PDT therapeutic index between GBM and normal intracranial tissues,
      as well as to improve contrast in fluorescence guided resection.

PMID- 24037827
TI  - Why I may be antisocial, or the value added by editing.

PMID- 24037826
TI  - Delay discounting of monetary rewards over a wide range of amounts.
AB  - The present study examined delay discounting of hypothetical monetary rewards
      over a wide range of amounts (from $20 to $10 million) in order to determine how
      reward amount affects the parameters of the hyperboloid discounting function and
      to compare fits of the hyperboloid model with fits of two discounting models used
      in neuroeconomics: the quasi-hyperbolic and the double-exponential. Of the three
      models assessed, the hyperboloid provided the best fit to the delay discounting
      data. The present delay discounting results may be compared to those of a
      previous study on probability discounting (Myerson, Green, & Morris, 2011) that
      used the same extended range of amounts. The hyperboloid function accurately
      described both types of discounting, but reward amount had opposite effects on
      the degree of discounting. Importantly, the amount of delayed reward affected the
      rate parameter of the hyperboloid discounting function but not its exponent,
      whereas the opposite was true for the amount of probabilistic reward. The finding
      that the exponent of the hyperboloid discounting function remains relatively
      constant across a wide range of delayed amounts provides strong support for a
      psychophysical scaling interpretation, and stands in stark contrast to the
      finding that the exponent of the hyperboloid function increases with the amount
      of probabilistic reward. Taken together, these findings argue that delay and
      probability discounting involve fundamentally different decision-making
      mechanisms. 

PMID- 24037828
TI  - A snapshot of inpatient cancer rehabilitation.

PMID- 24037829
TI  - Pharmaceutical development and regulatory considerations for nanoparticles and
      nanoparticulate drug delivery systems.
AB  - Pharmaceutical nanomaterials (NMs) encompass a wide variety of materials
      including drug nanoparticles (NPs), which can be amorphous or crystalline; or
      nanoparticulate drug delivery systems, such as micelles, microemulsions,
      liposomes, drug-polymer conjugates, and antibody-drug conjugates. These NMs are
      either transient or persistent-depending on whether the integrity of their
      structure and size is maintained until reaching the site of drug action. Examples
      of several approved drug products are included as pharmaceutical nanoparticulate
      systems along with a commentary on the current development issues and paradigms
      for various categories of NPs. This commentary discusses the preparation of
      nanoparticulate systems for commercial development, and the biopharmaceutical and
      pharmacokinetic advantages of these systems. A criterion of criticality is
      defined that incorporates the structure, in addition to size requirement of
      pharmaceutical NPs to identify systems that may require special development and
      regulatory considerations.

PMID- 24037830
TI  - A validated HPLC-MS/MS method for determination of genipin-1-o-glucuronic acid in
      rat plasma after administration of genipin and its application to a
      pharmacokinetic study.
AB  - A sensitive and specific method was developed and validated for the quantitation
      of one major metabolite of genipin in rats plasma. The major metabolite was
      isolated from rat bile via semi-preparative HPLC technology and its chemical
      structure was identified as genipin-1-o-glucuronic acid (GNP-GLU), which was for
      the first time used as a standard compound for quantitative analysis in rat
      plasma after administration of genipin. The application of high-performance
      liquid chromatography-tandem mass spectrometry in negative mode in multiple
      reaction monitoring mode was investigated. Chromatographic separation was
      achieved on an Eclipse XDB-C18 column using a mobile phase consisting of water
      with 0.1% formic acid (A)-acetonitrile (B). The limit of detecation was 0.214
      ng/mL and the lower limit of quantification was 0.706 ng/mL. The calibration
      curve was linear from 1.27 to 3810 ng/mL for plasma samples, with a correlation
      coefficient of 0.9924. The intra- and inter-day precisions and accuracy were all
      within 15%. The recoveries of GNP-GLU and puerarin were above 90.0 and 76.2%,
      respectively. The highly sensitive method was successfully applied to estimate
      pharmacokinetic parameters of GNP-GLU following oral and intravenous
      administration of genipin to rats.

PMID- 24037831
TI  - Role of Hippo signaling in cancer stem cells.
AB  - Cancer stem cells (CSCs) have been proposed and evidenced as the initiator of
      tumor formation and the seeds of metastases. Thereby, the molecular mechanisms
      regarding modulation of CSCs have been widely explored, aimed to improve
      treatment for cancer patients. Recent progress has highlighted the effects of
      Hippo signaling in tumorigenesis and cancer development, including its crucial
      role in CSC regulation. Although the kernel Hippo signaling cascade has been well
      studied, its upstream inputs and downstream transcriptional regulation still
      remain elusive. In this review, we summarize the current understanding of the
      mechanism and regulatory function of Hippo signaling in CSCs, with emphasis on
      its possible roles in regulation of CSC self-renewal, differentiation and
      tumorigenesis.

PMID- 24037832
TI  - Effects of electromagnetic fields emitted from W-CDMA-like mobile phones on sleep
      in humans.
AB  - In this study, we investigated subjective and objective effects of mobile phones
      using a Wideband Code Division Multiple Access (W-CDMA)-like system on human
      sleep. Subjects were 19 volunteers. Real or sham electromagnetic field (EMF)
      exposures for 3 h were performed before their usual sleep time on 3 consecutive
      days. They were exposed to real EMF on the second or third experimental day in a
      double-blind design. Sleepiness and sleep insufficiency were evaluated the next
      morning. Polysomnograms were recorded for analyses of the sleep variables and
      power spectra of electroencephalograms (EEG). No significant differences were
      observed between the two conditions in subjective feelings. Sleep parameters
      including sleep stage percentages and EEG power spectra did not differ
      significantly between real and sham exposures. We conclude that continuous wave
      EMF exposure for 3 h from a W-CDMA-like system has no detectable effects on human
      sleep.

PMID- 24037833
TI  - Human monoclonal antibodies: the residual challenge of antibody immunogenicity.
AB  - One of the major reasons for seeking human monoclonal antibodies has been to
      eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet
      been no approach which absolutely abolishes that risk for cell-binding
      antibodies. In this short article, I draw attention to classical work which shows
      that monomeric immunoglobulins are intrinsically tolerogenic if they can be
      prevented from creating aggregates or immune complexes. Based on these classical
      studies two approaches for active tolerization to therapeutic antibodies are
      described. 

PMID- 24037834
TI  - Technical and ethical limitations in making human monoclonal antibodies (an
      overview).
AB  - In the broadest sense there are no longer any technical limitations to making
      human mAbs. Biological issues involving the type and nature of either a synthetic
      or a natural antibody, advantages of various B cell immunological compartments,
      and various assays needed to qualitate and quantitate mAbs have essentially been
      solved. If the target antigen is known then procedures to optimize antibody
      development can be readily planned out and implemented. When the antigen or
      target is unknown and specificity is the driving force in generating a human mAb
      then considerations about the nature and location of the B cell making the sought
      after antibody become important. And, therefore, the person the B cell is
      obtained from can be an ethical challenge and a limitation. For the sources of B
      cells special considerations must be taken to insure the anonymity and privacy of
      the patient. In many cases informed consent is adequate for antibody development
      as well as using discarded tissues. After the antibody has been generated then
      manufacturing technical issues become important that greatly depend upon the
      amounts of mAb required. For kilogram quantities then special considerations for
      manufacturing that include FDA guidelines will be necessary. 

PMID- 24037835
TI  - Therapeutic human monoclonal antibodies in inflammatory diseases.
AB  - Monoclonal antibodies (mAbs) are antibodies of a single antigen specificity
      produced by identical immune cells, i.e., clones of a common germ cell. They
      offer unprecedented opportunities to drug development because of their ability to
      target almost any cell surface or secreted molecule with remarkable efficacy and
      safety. In this chapter, the application of human mAbs in the treatment of
      inflammatory diseases is reviewed. We discuss in detail several mAb-based drugs
      such as anti-tumor necrosis factor (anti-TNF), anti-interleukin-1 (anti-IL-1)
      receptor, anti-IL-6 receptor, anti-alpha4 integrin subunit, and anti-CD20 agents,
      all of which have been documented by clinical trials to be efficacious and have
      been approved for the therapy of several inflammatory and immune diseases,
      including rheumatoid arthritis, Crohn's disease, ulcerative colitis,
      spondyloarthropathies, juvenile arthritis, psoriasis, psoriatic arthritis, and
      others. These novel drugs can be used either as a monotherapy or in combination
      with other conventional therapeutic modalities, particularly if the disease under
      treatment is refractory to therapy using solely conventional techniques. As a
      large variety of mAb-based agents targeting a plethora of cytokines, chemokines,
      adhesion and co-stimulatory molecules, receptors, as well as diverse cell types,
      are presently under investigation, the therapeutic armamentarium of the clinician
      is expected to greatly broaden in the near future, providing improved patient
      care for a wide range of devastating diseases of our times. 

PMID- 24037836
TI  - Therapeutic human monoclonal antibodies against cancer.
AB  - There are over 30 monoclonal antibodies that are FDA approved for a variety of
      diseases ranging from malignancies to autoimmune diseases to macular
      degeneration. These antibodies include murine, fully humanized, and chimeric
      antibodies. There are a number of monoclonal antibodies used in the treatment of
      malignancies; in fact, three of the top five grossing antibodies (bevacizumab,
      trastuzumab, and rituximab) are used in oncology Scolnik (mAbs 1:179-184, 2009). 

PMID- 24037837
TI  - Polyclonal and monoclonal antibodies in clinic.
AB  - Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains
      added to amino-acid residues by N-linked glycosylation and occasionally by O
      linked glycosylation. The versatility of antibodies is demonstrated by the
      various functions that they mediate such as neutralization, agglutination,
      fixation with activation of complement and activation of effector cells.
      Naturally occurring antibodies protect the organism against harmful pathogens,
      viruses and infections. In addition, almost any organic chemical induces antibody
      production of antibodies that would bind specifically to the chemical. These
      antibodies are often produced from multiple B cell clones and referred to as
      polyclonal antibodies. In recent years, scientists have exploited the highly
      evolved machinery of the immune system to produce structurally and functionally
      complex molecules such as antibodies from a single B clone, heralding the era of
      monoclonal antibodies. Most of the antibodies currently in the clinic, target
      components of the immune system, are not curative and seek to alleviate symptoms
      rather than cure disease. Our group used a novel strategy to identify reparative
      human monoclonal antibodies distinct from conventional antibodies. In this
      chapter, we discuss the therapeutic relevance of both polyclonal and monoclonal
      antibodies in clinic. 

PMID- 24037838
TI  - Production of human monoclonal antibodies by the epstein-barr virus method.
AB  - Epstein-Barr virus (EBV) is a herpes virus which in vitro efficiently
      immortalizes nearly all human B lymphocytes. The lymphoblastoid diploid cell
      lines (LCL's) thus generated preserve the characteristics of the cells initially
      infected by the virus: the cells produce and secrete immunoglobulins and also
      express these molecules on their surface. A selection of specific antibody
      producing cells (i.e., antigen-committed cells) before EBV-infection or when
      LCL's have already been established, enables isolation of monoclonal cell lines
      that secrete specific antibodies. If selection of antigen-committed cells is not
      feasible, secretion of specific antibodies by cloned LCL's in limiting dilution
      cultures enables isolation of the desired cell lines. The method allows the
      production of human IgM, IgG, IgA, and IgE monoclonal antibodies from any
      individual. Monoclonal antibodies produced by the EBV method resemble the
      antibody repertoire of the donor of the lymphocytes. Human monoclonal antibodies
      are promising reagents for passive immunization. 

PMID- 24037839
TI  - Humanization and simultaneous optimization of monoclonal antibody.
AB  - Antibody humanization is an essential technology for reducing the potential risk
      of immunogenicity associated with animal-derived antibodies and has been applied
      to a majority of the therapeutic antibodies on the market. For developing an
      antibody molecule as a pharmaceutical at the current biotechnology level,
      however, other properties also have to be considered in parallel with
      humanization in antibody generation and optimization. This section describes the
      critical properties of therapeutic antibodies that should be sufficiently
      qualified, including immunogenicity, binding affinity, physiochemical stability,
      expression in host cells and pharmacokinetics, and the basic methodologies of
      antibody engineering involved. By simultaneously optimizing the antibody molecule
      in the light of these properties, it should prove possible to shorten the
      research and development period necessary to identify a highly qualified clinical
      candidate and consequently accelerate the start of the clinical trial. 

PMID- 24037840
TI  - Chimeric antibodies.
AB  - Here we describe a detailed protocol for the one-step preparation of antigen
      specific human chimeric immunoglobulin G (IgG) monoclonal antibodies (mAbs) using
      an in vitro antibody design method referred to as the ADLib (Autonomously
      Diversifying Library) system. This method employs a chicken B cell line DT40
      based library in which the variable regions of the Ig gene loci have been highly
      diversified by treatment with the histone deacetylase inhibitors. DT40 cells
      express both membrane-bound and secreted forms of chicken IgM. This property
      allows a rapid screening and selection of antibody-producing B cells from the
      library by using magnetic beads conjugated with any antigen of interest. To apply
      the ADLib system to the direct generation of human chimeric antibody, we have
      inserted a DNA segment coding for the constant region of human IgG into the
      chicken IgM heavy-chain locus of DT40 cells by homologous gene targeting. By a
      mechanism of alternative splicing, the resulting DT40 strain simultaneously
      expresses chimeric human IgG that contain the same Ig variable region sequences
      as the membrane-bound chicken IgM displayed at the cell surface. Application of
      the ADLib system to this human Ig-inserted DT40 strain enables the one-step
      isolation of human chimeric IgG that is specific for any antigen of interest and
      can be easily purified for immediate use. 

PMID- 24037841
TI  - Recombinant genetic libraries and human monoclonal antibodies.
AB  - In order to comprehensively manipulate the human proteome we require a vast
      repertoire of pharmacological reagents. To address these needs we have developed
      repertoires of synthetic antibodies by phage display, where diversified
      oligonucleotides are used to modify the complementarity-determining regions
      (CDRs) of a human antigen-binding fragment (Fab) scaffold. As diversity is
      produced outside the confines of the mammalian immune system, synthetic antibody
      libraries allow us to bypass several limitations of hybridoma technology while
      improving the experimental parameters under which pharmacological reagents are
      produced. Here we describe the methodologies used to produce synthetic antibody
      libraries from a single human framework with diversity restricted to four CDRs.
      These synthetic repertoires can be extremely functional as they produce highly
      selective, high affinity Fabs to the majority of soluble human antigens. Finally
      we describe selection methodologies that allow us to overcome immuno-dominance in
      our selections to target a variety of epitopes per antigen. Together these
      methodologies allow us to produce human monoclonal antibodies to manipulate the
      human proteome. 

PMID- 24037842
TI  - Production of stabilized scFv antibody fragments in the E. coli bacterial
      cytoplasm.
AB  - Monoclonal antibodies (mAbs) are currently the fastest growing class of
      therapeutic proteins. Parallel to full-length IgG format the development of
      recombinant technologies provided the production of smaller recombinant antibody
      variants. The single-chain variable fragment (scFv) antibody is a minimal form of
      functional antibody comprised of the variable domains of immunoglobulin light and
      heavy chains connected by a flexible linker. In most cases, scFvs are expressed
      in the bacterium E. coli. The production of soluble scFvs under the reducing
      conditions of the E. coli bacterial cytoplasm is inefficient because of the
      inability of the disulfide bonds to form. Hence, scFvs are either secreted to the
      periplasm as soluble proteins or expressed in the cytoplasm as insoluble
      inclusion bodies and recovered by refolding. The cytoplasmic expression of scFvs
      as a C-terminal fusion to maltose-binding protein (MBP) provided the high-level
      production of stable, soluble, and functional fusion protein. The below protocol
      provides the detailed description of MBP-scFv production in E. coli utilizing two
      expression systems: pMalc-TNN and pMalc-NHNN. Although the MBP tag does not
      disrupt the most of antibody activities, the MBP-TNN-scFv product can be cleaved
      by TEV protease in order to obtain untagged scFv. 

PMID- 24037843
TI  - Construction and production of an IgG-Like tetravalent bispecific antibody, IgG
      single-chain Fv fusion.
AB  - In recent years, both laboratory and clinical studies have demonstrated that
      bispecific antibodies (BsAbs) may have significant potential application in
      cancer therapy either by targeting tumor cells with cytotoxic agents including
      effector cells, radionuclides, drugs, and toxins, or by simultaneously blocking
      two tumor-associated targets, e.g., tumor growth factors and/or their cell
      surface receptors. A major obstacle in the development of BsAb has been the
      difficulty of producing the materials in sufficient quality and quantity by
      traditional technologies such as the hybrid hybridoma and chemical conjugation
      methods. The development of recombinant BsAbs as therapeutic agents will depend
      heavily on the advances made in the design of the constructs (or formats) and
      production efficiency. Here we describe a recombinant method for the construction
      and production of a tetravalent IgG-like BsAb molecule, IgG-scFv fusion, in
      which, a single-chain Fv (scFv) antibody fragment of one antigen specificity is
      genetically fused to the c-terminal of a conventional IgG of a different antigen
      specificity. 

PMID- 24037844
TI  - Construction of human antibody gene libraries and selection of antibodies by
      phage display.
AB  - Antibody phage display is the most commonly used in vitro selection technology
      and has yielded thousands of useful antibodies for research, diagnostics, and
      therapy.The prerequisite for successful generation and development of human
      recombinant antibodies using phage display is the construction of a high-quality
      antibody gene library. Here, we describe the methods for the construction of
      human immune and naive scFv gene libraries.The success also depends on the
      panning strategy for the selection of binders from these libraries. In this
      article, we describe a panning strategy that is high-throughput compatible and
      allows parallel selection in microtiter plates. 

PMID- 24037845
TI  - Antigen-specific human monoclonal antibodies from transgenic mice.
AB  - Due to the difficulties found when generating fully human monoclonal antibodies
      (mAbs) by the traditional method, several efforts have attempted to overcome
      these problems, with varying levels of success. One approach has been the
      development of transgenic mice carrying immunoglobulin (Ig) genes in germ line
      configuration. The engineered mouse genome can undergo productive rearrangement
      in the B cell population, with the generation of mouse B lymphocytes expressing
      human Ig (hIg) chains. To avoid the expression of mouse heavy or light chains,
      the endogenous mouse Ig (mIg) loci must be silenced by gene-targeting techniques.
      Subsequently, to obtain antigen-specific mAbs, conventional immunization
      protocols can be followed and the mAb technique used (fusion of activated B cells
      with mouse myeloma cells, screening, cloning, freezing, and testing) with these
      animals expressing human Ig genes. This chapter describes the type of transgenic
      knockout mice generated for various research groups, provides examples of human
      mAbs developed by research groups and companies, and includes protocols of
      immunization, generation, production, and purification of human mAbs from such
      mice. In addition, it also addresses the problems detected, and includes some of
      the methods that can be used to analyze functional activities with human mAbs. 

PMID- 24037846
TI  - Phage display technology for human monoclonal antibodies.
AB  - During the last 15 years in vitro technologies opened powerful routes to combine
      the generation of large libraries together with fast selection procedures to
      identify lead candidates. One of the commonest methods is based on the use
      filamentous phages. Antibodies (Abs) can be displayed successfully on the surface
      of phage by fusing the coding sequence of the antibody variable (V) regions to
      the phage minor coat protein pIII. By creating large libraries, antibodies with
      affinities comparable to those obtained using traditional hybridomas technology
      can be selected by a series of cycles of selection on antigen. As in this system
      antibody genes are cloned simultaneously with selection they can be easily
      further engineered for example by increasing their affinity (to levels
      unobtainable in the immune system), modulating their specificity or their
      effector function (by recloning into a full-length immunoglobulin scaffold). This
      chapter describes the basic protocols for antibody library construction,
      handling, and selection. 

PMID- 24037847
TI  - Antigen-specific in vitro immunization: a source for human monoclonal antibodies.
AB  - Human monoclonal antibody has great potential for treatment of various diseases
      utilizing their specificity against antigens. We have shown an in vitro
      immunization (IVI) protocol inducing antigen-specific immune responses in human
      peripheral blood mononuclear cells (PBMCs) for efficient production of human
      monoclonal antibodies. By using IVI method antigen specific antibody genes can be
      efficiently obtained because of increasing production of antigen-specific
      antibodies from in vitro immunized PBMCs. This IVI protocol will be widely
      applied for combination with several display methods and enhance the production
      of human monoclonal antibodies. 

PMID- 24037848
TI  - Methods for radiolabelling of monoclonal antibodies.
AB  - The use of radionuclide labels allows to study the pharmacokinetics of monoclonal
      antibodies, to control the specificity of their targeting and to monitor the
      response to an antibody treatment with high accuracy. Selection of label depends
      on the processing of an antibody after binding to an antigen, and on the
      character of information to be derived from the study (distribution of antibody
      in the extracellular space, target occupancy or determination of sites of
      metabolism). This chapter provides protocols for labelling of antibodies with
      iodine-125 (suitable also for other radioisotopes of iodine) and with indium-111.
      Since radiolabelling might damage and reduce the immunoreactive fraction and/or
      affinity of an antibody, the methods for assessment of these characteristics of
      an antibody are provided for control. 

PMID- 24037849
TI  - Purification of human monoclonal antibodies and their fragments.
AB  - This chapter summarizes the most common chromatographic mAb and mAb fragment
      purification methods, starting by elucidating the relevant properties of the
      compounds and introducing the various chromatography modes that are available and
      useful for this application. A focus is put on the capture step affinity and ion
      exchange chromatography. Aspects of scalability play an important role in judging
      the suitability of the methods. The chapter introduces also analytical
      chromatographic methods that can be utilized for quantification and purity
      control of the product. In the case of mAbs, for most purposes the purity
      obtained using an affinity capture step is sufficient. Polishing steps are
      required if material of particularly high purity needs to be generated. For mAb
      fragments, affinity chromatography is not yet fully established, and the capture
      step potentially may not provide material of high purity. Therefore, the
      available polishing techniques are touched upon briefly. In the case of mAb
      isoform and bispecific antibody purification, countercurrent chromatography
      techniques have been proven to be very useful and a part of this chapter has been
      dedicated to them, paying tribute to the rising interest in these antibody
      formats in research and industry. 

PMID- 24037850
TI  - Idiotype-specific intravenous immunoglobulin (IVIG) for therapy of autoimmune
      diseases.
AB  - Intravenous immunoglobulin (IVIG) is used successfully for therapy of
      inflammatory and autoimmune diseases, especially in cases of conventional therapy
      resistance. Within the broad spectrum of immunomodulatory activities of IVIG in
      vitro and in vivo, the anti-idiotypic activity, neutralizing the autoimmune
      disease related idiotypes, is one of the main mechanism. We and others have
      proven that from the IVIG composition, diverse fractions of autoimmune disease
      specific IVIG can be affinity purified (sIVIG). This sIVIG was shown to be more
      efficient than the whole compound of IVIG in experimental animal models of
      autoimmune diseases.The affinity purification of disease sIVIG encompasses three
      stages. The first stage is to construct an autoantigen column for affinity
      purification of the autoantibodies. In the second stage the purified
      autoantibodies are used to construct a new column composed of the autoantibodies.
      The later is utilized for affinity purification of anti-autoantibodies (anti-
      idiotypes) IVIG defined as autoimmune disease specific IVIG- sIVIG. 

PMID- 24037851
TI  - Frequent mental distress (FMD) in Irish Travellers: discrimination and
      bereavement negatively influence mental health in the All Ireland Traveller
      Health Study.
AB  - Travellers are an indigenous minority group in Ireland, with poorer life
      expectancy and health status than the general population. Recent data have shown
      that Travellers are at increased risk of poor mental health and sequelae from
      same. We aimed to examine the associations between sociodemographic and lifestyle
      factors with poor mental health in Irish Travellers. A census survey of all
      Travellers was undertaken, with 8,492 enumerated families (80% response rate). A
      random subset of 1,796 adults completed an adult health survey. Traveller peer
      researchers employed a novel oral-visual computer-aided data collection tool.
      Frequent mental distress (FMD) was defined as 14 or more days of poor mental
      health in the preceding 1 month. Prevalence ratios for typical associates of FMD
      were estimated using a Poisson regression model, adjusted for age and sex. FMD
      was present in 11.9% of Traveller respondents, and prevalence increased with age.
      After age and sex adjustment, FMD was more prevalent in those whose quality of
      life was impaired by physical health, by those who were recently bereaved of a
      friend or family member, and by those who had greater experiences of
      discrimination. This study shows that Travellers experience discrimination and
      bereavement, which negatively influence their mental health. The findings have
      implications for the mental healthcare needs of indigenous ethnic minorities
      worldwide. 

PMID- 24037852
TI  - Delayed reinforcement and fixed-ratio performance.
AB  - Effects of delayed reinforcement on fixed-ratio (FR) maintained responding of
      pigeons were investigated. In Experiments 1-3, the delay of reinforcement was
      increased across successive sessions until pigeons paused for 300 s. Both
      signaled and unsignaled delays were studied across different conditions. Overall
      response rates and run rates (timed from the first to last response of a ratio)
      decreased and postreinforcement pauses increased as delays increased in each
      experiment. As delays increased, the likelihood of pausing during a ratio run
      also increased. When these measures were plotted as a function of obtained
      delays, signaled delays had less of an effect on the above measures than did
      unsignaled ones. In Experiment 2, delays had a greater effect on the above
      measures than did a control condition arranging equivalent interreinforcer
      intervals to those accompanying the delays. Experiments 3 and 4 examined the
      generality of the effects obtained in the first two experiments. In Experiment 3,
      delays imposed on FR or yoked-interval schedules had similar behavioral effects.
      In Experiment 4, effects similar to those found in Experiments 1-3 for 1, 10, and
      20-s delays imposed on FR 50 schedules were found when the FR requirement
      increased across sessions. Despite the different contingencies relating response
      rate and reinforcement rates on interval and ratio schedules, delays of
      reinforcement generally affect performance on these schedules similarly. 

PMID- 24037853
TI  - Recovery of intrinsic fluorescence from single-point interstitial measurements
      for quantification of doxorubicin concentration.
AB  - BACKGROUND AND OBJECTIVE: We developed a method for the recovery of intrinsic
      fluorescence from single-point measurements in highly scattering and absorbing
      samples without a priori knowledge of the sample optical properties. The goal of
      the study was to demonstrate accurate recovery of fluorophore concentration in
      samples with widely varying background optical properties, while simultaneously
      recovering the optical properties. MATERIALS AND METHODS: Tissue-simulating
      phantoms containing doxorubicin, MnTPPS, and Intralipid-20% were created, and
      fluorescence measurements were performed using a single isotropic probe. The
      resulting spectra were analyzed using a forward-adjoint fluorescence model in
      order to recover the fluorophore concentration and background optical properties.
      RESULTS: We demonstrated recovery of doxorubicin concentration with a mean error
      of 11.8%. The concentration of the background absorber was recovered with an
      average error of 23.2% and the scattering spectrum was recovered with a mean
      error of 19.8%. CONCLUSION: This method will allow for the determination of local
      concentrations of fluorescent drugs, such as doxorubicin, from minimally invasive
      fluorescence measurements. This is particularly interesting in the context of
      transarterial chemoembolization (TACE) treatment of liver cancer.

PMID- 24037854
TI  - To preserve or not to preserve: how difficult is the decision about fertility
      preservation?
AB  - BACKGROUND: The decision to pursue fertility preservation (FP) after a cancer
      diagnosis is complex. We examined the prevalence of high decisional conflict and
      specific factors that influence this decision using the Decisional Conflict Scale
      (DCS). METHODS: The FIRST project is a web-based survey of female cancer
      survivors (ages 18-44 years) who have undergone gonadotoxic treatment. We
      evaluated the association between recalled decisional conflict and referral to FP
      counseling and demographic, socioeconomic, and cancer variables. RESULTS: Of 208
      participants, 115 subjects (55%) had scores consistent with high decisional
      conflict (DCS score >37.5 of 100), and 43 (21%) were in the moderate range (25
      37.5). In unadjusted analysis, high decisional conflict was associated with lack
      of referral to FP consultation, not undergoing FP treatment, concerns regarding
      FP cost, length of survivorship, lower income, education, partner status, and
      cancer type. In multivariable analysis, significantly higher prevalence of high
      decisional conflict was observed in participants who were not referred for FP
      consultation (prevalence ratio [PR], 1.25; 95% confidence interval [CI], 1.06
      1.47), as well as in participants who reported cost of FP services to be
      prohibitive (PR, 1.16 [95% CI, 1.03-1.31]). Prevalence of high DCS was lower for
      women who underwent FP treatment (PR, 0.67 [95% CI, 0.52-0.86]). CONCLUSIONS: In
      this study of female young adult cancer survivors, the majority recalled
      significant decisional conflict about FP at cancer diagnosis. Increasing access
      to FP via referral for counseling and cost reduction may decrease decisional
      conflict about FP for young patients struggling with cancer and fertility
      decisions.

PMID- 24037855
TI  - Gankyrin promotes tumor growth and metastasis through activation of IL-6/STAT3
      signaling in human cholangiocarcinoma.
AB  - Although gankyrin is involved in the tumorigenicity and metastasis of some
      malignancies, the role of gankyrin in cholangiocarcinoma (CCA) is unclear. In
      this study we investigated the expression of gankyrin in human CCA tissues and
      cell lines. The effects of gankyrin on CCA tumor growth and metastasis were
      determined both in vivo and in vitro. The results showed that gankyrin was
      overexpressed in CCA tissues and cell lines. Gankyrin expression was associated
      with CCA histological differentiation, TNM stage, and metastasis. The
      multivariate Cox analysis revealed that gankyrin was an independent prognostic
      indicator for overall survival. Gankyrin overexpression promoted CCA cell
      proliferation, migration, and invasion, while gankyrin knockdown inhibited CCA
      tumor growth, metastasis, and induced Rb-dependent senescence and G1 phase cell
      cycle arrest. Gankyrin increased the phosphorylation of signal transducer and
      activator of transcription 3 (STAT3) and promoted the nuclear translocation of p
      STAT3. Suppression of STAT3 signaling by small interfering RNA (siRNA) or STAT3
      inhibitor interfered with gankyrin-mediated carcinogenesis and metastasis, while
      interleukin (IL)-6, a known upstream activator of STAT3, could restore the
      proliferation and migration of gankyrin-silenced CCA cells. The IL-6 level was
      decreased by gankyrin knockdown, while increased by gankyrin overexpression.
      Gankyrin regulated IL-6 expression by way of facilitating the phosphorylation of
      Rb; meanwhile, rIL-6 treatment increased the expression of gankyrin, suggesting
      that IL-6 was regulated by a positive feedback loop involving gankyrin in CCA. In
      the xenograft experiments, gankyrin overexpression accelerated tumor formation
      and increased tumor weight, whereas gankyrin knockdown showed the opposite
      effects. The in vivo spontaneous metastasis assay revealed that gankyrin promoted
      CCA metastasis through IL-6/STAT3 signaling pathway. CONCLUSION: Gankyrin is
      crucial for CCA carcinogenesis and metastasis by activating IL-6/STAT3 signaling
      pathway through down-regulating Rb protein.

PMID- 24037856
TI  - Quantitative profiling method for phytohormones and betaines in algae by liquid
      chromatography electrospray ionization tandem mass spectrometry.
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
      for the quantitative determination of phytohormones and betaines in algae. The
      results showed that phytohormones and betaines were separated with high
      efficiency on Hypersil Gold C18 and Cnwsil SCX columns. Mass spectrometric
      detection was performed using positive or negative electrospray ionization in
      selective reaction monitoring mode (SRM). Linearity of the method was good with
      correlation coefficients (r(2) > 0.9951 in the range of 0.005-5 mg/L. The limits
      of detection were from 0.004 to 0.86 ug/L and the limits of quantification were
      in the range from 0.01 to 2.8 ug/L for the investigated phytohormones and
      betaines. The obtained recoveries varied between 61.33 and 90.39%, and the
      relative standard deviations were <15%. Using the developed methods, seven types
      of phytohormones and two types of betaines in Laminaria japonica, and seven types
      of phytohormones and one type of betaine in Pyropia haitanensis, which were
      collected in Xiangshan, Zhejiang Province, China, were determined. Thus, LC-MS/MS
      was demonstrated to be a powerful tool for the comprehensive analysis of
      phytohormones and betaines in algae, owing to its large dynamic range and
      excellent sensitivity.

PMID- 24037857
TI  - US casino boss challenges Spain's smoking ban.

PMID- 24037858
TI  - Global Fund needs $15bn to fight HIV, tuberculosis, and malaria.

PMID- 24037859
TI  - Nuclear power plants do not raise risk of leukaemia in children, study finds.

PMID- 24037860
TI  - Mentally ill patient chained to tree to highlight shortage of psychiatric beds in
      India.

PMID- 24037861
TI  - Evaluation of drug crystallinity in aqueous suspension using terahertz time
      domain attenuated total reflection spectroscopy.
AB  - Terahertz pulsed spectroscopy has recently been demonstrated to be a novel
      technique for the investigation of the solid-state properties of pharmaceutical
      materials. In this study, we directly measured the crystallinity of a drug
      suspended in water, using a terahertz pulsed attenuated total reflection (ATR)
      method. The dihydropyridine calcium channel blocker nifedipine is classified as a
      poorly soluble drug; its most stable crystalline form is known as form I.
      Transmission spectra, collected from 0.2 to 2.0 THz (6.6 to 66 cm(-1) ), of
      nifedipine crystals had a strong absorption peak at 1.2 THz (40 cm(-1) ) at room
      temperature. When the nifedipine crystals were mixed with poloxamer 188 and
      suspended in water, the resulting spectra measured using the ATR method had a
      peak at the same frequency as in the spectra obtained in transmission mode.
      Furthermore, the peak area was proportional to the amount of crystals. The upward
      sloping baseline in the spectra, corresponding to water absorption, decreased
      stepwise with increasing amounts of crystalline particles. We confirmed that the
      spectra gave excellent quantitative results, using partial least-squares
      regression analysis. The results suggest the possibility of using this method for
      qualitative and quantitative assessments of crystalline drugs in suspension.

PMID- 24037863
TI  - Vaccine prevention of meningococcal disease in adolescents and travellers.

PMID- 24037864
TI  - New guidelines and the development of an international consensus on
      recommendations for the antibiotic prophylaxis of infective endocarditis.
AB  - During the last five years there has been a considerable change in attitude
      towards antibiotic prophylaxis of endocarditis in many countries so that far
      fewer cardiac patients are advised to receive prophylaxis in comparison with
      previous years. Much greater emphasis is now given to the maintenance of good
      oral hygiene as the main method of preventing endocarditis and prophylaxis is
      only recommended for patients with the highest risk cardiac conditions undergoing
      dental procedures. Most countries have now abandoned prophylaxis for urological
      and gastrointestinal procedures. The UK National Institute for Health and
      Clinical Excellence guidance, which does not recommend prophylaxis for any group
      of patients undergoing dental procedures, is regarded as too extreme by many
      experts in other countries. The assertion that more patients would die from fatal
      anaphylaxis after oral amoxicillin, the main prophylactic agent, than would die
      from endocarditis because prophylaxis is withheld, may not be correct since the
      risks of dying after oral amoxicillin have probably been overestimated. There is
      a lack of clinical evidence either for or against the efficacy of antibiotic
      prophylaxis. Unless convincing data is obtained from future research any new
      international consensus guidelines will continue to be based mainly on expert
      opinion rather than on good evidence. 

PMID- 24037862
TI  - Advances in androgen receptor targeted therapy for prostate cancer.
AB  - Prostate cancer (PCa) is the second leading cause of cancer death in men. Current
      research findings suggest that the androgen receptor (AR) and its signaling
      pathway contribute significantly to the progression of metastatic PCa. The AR is
      a ligand activated transcription factor, where androgens such as testosterone (T)
      and dihydroxytestosterone (DHT) act as the activating ligands. However in many
      metastatic PCa, the AR functions promiscuously and is constitutively active
      through multiple mechanisms. Inhibition of enzymes that take part in androgen
      synthesis or synthesizing antiandrogens that can inhibit the AR are two popular
      methods of impeding the androgen receptor signaling axis; however, the inhibition
      of androgen-independent activated AR function has not yet been fully exploited.
      This article focuses on the development of emerging novel agents that act at
      different steps along the androgen-AR signaling pathway to help improve the poor
      prognosis of PCa patients.

PMID- 24037865
TI  - Knowledge, skills, and productivity in primary eye care among health workers in
      Tanzania: need for reassessment of expectations?
AB  - The aim of this study was to assess the primary eye care knowledge, skills, and
      productivity of primary health workers at dispensaries in a district in Tanzania.
      Factors likely to contribute to knowledge, skills, and productivity were also
      assessed. A descriptive cross-sectional study design was used. All health workers
      employed at government dispensaries in Mwanga District, Kilimanjaro Region,
      Tanzania were included. A skills score of respondents, comprising knowledge and
      ability to test visual acuity and diagnosis and management of common eye
      conditions, was measured through interview and direct observation. Factors
      associated with the skills score were assessed. Forty nine health workers were
      assessed. There was poor understanding of basic ocular conditions and how to
      assess visual acuity; the mean skills score of all respondents was 6.2 out of 12.
      There was little association between having received training and the skills
      score. The mean number of eye patients managed per health worker was three per
      month. Findings suggest that a reassessment of the roles and responsibilities in
      primary eye care of dispensary health workers, review of training curriculum and
      teaching, and supervisory procedures may be necessary. 

PMID- 24037866
TI  - Effect on treatment coverage of adding community-directed treatment to the health
      facility-based approach of delivering anthelminthic drugs to under-five children
      during child health week in Mazabuka District, Zambia.
AB  - The current approach of delivering anthelminthic drugs to children aged 12-59
      months through health facilities during child health week (CHW) results in low
      treatment coverage in certain areas of Zambia. This study was designed to
      determine the impact on treatment coverage of adding community-directed treatment
      (ComDT) to the health facility (HF) approach. Treatment coverage was compared in
      two areas, one with the HF approach alone (HF area) and the other where ComDT was
      added to the HF approach (HF + ComDT area). Cross-sectional surveys were
      conducted every 6 months between June 2006 and December 2007 to monitor CHWs.
      chi(2) tests, odds ratios (OR) and their 95% CI were used to compare treatment
      coverage between and within each treatment arm. Addition of ComDT to the HF
      approach resulted in significantly higher treatment coverage in the HF + ComDT
      area compared with the HF area during CHW1, CHW2, CHW3 and CHW4, with ORs (and
      95% CIs) of a child being treated in the HF + ComDT area of 2.17 (1.90-2.48),
      3.07 (2.68-3.52), 11.17 (9.25-13.48) and 5.07 (4.27-6.01), respectively. We
      conclude that ComDT has the potential to raise treatment coverage significantly
      during CHWs. [ClinicalTrials.gov Identifier: NCT00349323]. 

PMID- 24037867
TI  - Challenges to implementation of artemisinin combination therapy policy in Uganda.
AB  - Uganda launched an artemisinin combination therapy (ACT) policy in 2006, using
      artemether-lumefantrine (AL) as first-line treatment for uncomplicated malaria,
      but insufficient information is available regarding its implementation. Semi
      structured interviews were conducted with key personnel: 32 clinical and four
      laboratory staff from 32 health centres (HCs) in Bushenyi and Iganga districts
      and the Ministry of Health. Structured interviews with 613 patients receiving
      malaria treatment at six randomly chosen HCs were held. Data were collected on
      availability of antimalarials, treatment guidelines, staffing and malaria
      treatment decisions. Posts for clinical staff were inadequately filled. Only 15
      (46.9%) HCs stocked AL for all weight categories. Nationwide, AL was out-of-stock
      March-July 2007. Twenty-one (65.6%) HCs stocked chloroquine. Out of 193 patients,
      177 (91.7%) used antimalarials other than AL before coming to HCs. The
      unrecommended antimalarials were mainly sourced from the private for profit (PFP)
      sector yet there were no guidelines regarding provision of AL in the PFP sector.
      Only 53/613 (8.6%) patients were examined for parasites and only 8 (15.1%) had a
      positive blood slide. The majority of the patients attending HCs (560; 91.4%)
      received antimalarials but only 323 (57.7%) received AL. In order to improve the
      implementation of the current policy, AL should be availed in adequate amounts at
      all points of care including the PFP sector; non-recommended drugs should be
      withdrawn from the market and it should be ensured that malaria is confirmed by
      laboratory diagnosis. STUDY REGISTRATION: Clinicaltrials.gov NCT00565071.

PMID- 24037868
TI  - Comparison of two village primary schools in northern Tanzania affected by
      fluorosis.
AB  - High fluoride levels in drinking water sources are a problem throughout the East
      African Rift Valley and can lead to dental fluorosis (DF) and skeletal fluorosis
      (SF) in exposed local populations. Two villages in the Hai District of northern
      Tanzania in which fluoride has been identified as a problem were investigated in
      a pilot study. Fluoride levels in drinking water sources were measured and the
      prevalence of DF and deformities due to SF were assessed in children attending
      school in the two villages. The assessment also recorded the source of drinking
      water as well as children's height, weight and 3-day food diaries. Over one
      quarter of the children in both villages had skeletal deformities, despite one
      village having much higher levels of fluoride in its drinking water sources. More
      than 90% of children in both villages had DF. SF and DF are major problems in
      this area. Deformities relating to SF are common, but the reasons for individual
      susceptibility remain unclear and may include a low calcium diet, ingestion of
      magadi (local salt) with high fluoride, or genetic factors. 

PMID- 24037869
TI  - Access to a blood test and antimalarials after introducing rapid diagnostic tests
      in rural Myanmar: initial experience in a malaria endemic area.
AB  - This study describes the use of a blood test, antimalarials and their
      determinants among 446 subjects with febrile illness in remote villages of Bago
      Division, Myanmar in 2006 after five months initialization of a rapid diagnostic
      test (RDT) and artemisinin-based combination therapy (ACT) programme. A
      structured questionnaire was used in a cross-sectional survey. Knowledge on
      malaria was asked of 357 key household respondents. The proportions of use of
      traditional medicine, modern medicine and both among febrile subjects were 31
      (7.0%), 247 (55.4%) and 168 (37.7%), respectively. A blood test was taken by
      41.0% of respondents and, of these, 81.4% were reported positive. Among 166
      artesunate users, 45.8% reported positive test results and 18.1% were self
      medicated. Only 37 (10.4%) key household respondents did not have misconceptions
      on malaria transmission. Predictors for having a blood test were being male (odds
      ratio [OR] = 1.96; 95% CI 1.20-3.22), having a higher knowledge on malaria (OR =
      1.77; 95% CI 1.03-3.06) and aged 50 years or above (OR = 0.32; 95% CI 0.13-0.78).
      Predictors for having both a blood test and using artesunate were being male (OR
      = 2.71; 95% CI 1.31-5.59) and having a higher knowledge on malaria (OR = 2.49;
      95% CI 1.27-4.92). The low coverage of proper clinical services and high
      prevalence of ineffective drug use confirmed the need for further strengthening
      of the programme. 

PMID- 24037870
TI  - Pica practice among pregnant women in the Kumasi metropolis of Ghana.
AB  - Pica, an eating disorder in which non-nutritional objects are frequently eaten,
      has negative health implications. Despite this, pica is less studied in many
      African communities where it is believed to be highly prevalent. This study
      therefore sought to determine the prevalence of pica and its various forms among
      pregnant women in Kumasi, Ghana, and the effects of education and place of
      residence (rural and urban) on pica practice. A random sample of pregnant women
      (n = 400) in rural and urban areas of Kumasi were interviewed using a
      questionnaire-based survey in 2008 and repeated in 2009. The results showed 47.0%
      of the pregnant women practising pica. Pagophagia accounted for 41.0%, followed
      by geophagia (29.8%), amylophagia (7.4%), plumbophagia (6.4%), and trichophagia
      (3.7%). Among the rural dwellers, 47.7% of the pregnant women practised pica
      during their pregnancies while 46.4% of the urban pregnant women engaged in the
      practice. Age and level of education did not significantly affect the practice of
      pica (P = 0.053 and P = 0.142 respectively). Also, 17.4% of the respondents
      identified a family member practising pica. Pica is therefore highly prevalent in
      pregnant women in Kumasi, with pagophagia and geophagia being the predominant
      types of pica. 

PMID- 24037871
TI  - Dengue prevention in southern Vietnam: Comment on: Householder perspectives and
      preferences on water storage and use, with references to dengue, in the Mekong
      Delta, southern Vietnam.

PMID- 24037872
TI  - Imaging EGFR and HER2 by PET and SPECT: a review.
AB  - In an effort to discover a noninvasive method for predicting which cancer
      patients will benefit from therapy targeting the EGFR and HER2 proteins, a large
      body of the research has been conducted toward the development of PET and SPECT
      imaging agents, which selectively target these receptors. We provide a general
      overview of the advances made toward imaging EGFR and HER2, detailing the
      investigation of PET and SPECT imaging agents ranging in size from small
      molecules to monoclonal antibodies. 

PMID- 24037875
TI  - Advances in inflammatory bowel disease pathogenesis: linking host genetics and
      the microbiome.
AB  - Studies of the genetics underlying inflammatory bowel diseases have increased our
      understanding of the pathways involved in both ulcerative colitis and Crohn's
      disease and focused attention on the role of the microbiome in these diseases.
      Full understanding of pathogenesis will require a comprehensive grasp of the
      delicate homeostasis between gut bacteria and the human host. In this review, we
      present current evidence of microbiome-gene interactions in the context of other
      known risk factors and mechanisms, and describe the next steps necessary to pair
      genetic variant and microbiome sequencing data from patient cohorts. We discuss
      the concept of dysbiosis, proposing that the functional composition of the gut
      microbiome may provide a more consistent definition of dysbiosis and may more
      readily provide evidence of genome-microbiome interactions in future exploratory
      studies. 

PMID- 24037876
TI  - Recent advances: Personalised use of current Crohn's disease therapeutic options.
AB  - Several aspects of the management of Crohn's disease (CD) are shared between
      patients. The goal of all therapies should be to achieve clinical and endoscopic
      remission in a timely manner to avoid disease progression and abdominal
      resections. The way this goal is achieved may differ and predicting how the
      disease will evolve, what the most appropriate therapy with the highest chance of
      success will be, how long a therapy needs to be continued, and what the intensity
      of follow-up should be are more difficult questions and require an individualised
      approach. Clinical parameters have been suggested to aid in the therapeutic
      decision process but lack specificity. Although much promise has been put in
      molecular markers, these have not yet found their way to the clinic. More
      recently, clinicians have started to gain interest in drug level monitoring to
      adapt doses of immunomodulators and/or anti-tumour necrosis factor antibodies in
      an individualised manner. An increasing number of studies show that therapeutic
      drug monitoring can help physicians to improve and personalise the management of
      their patients. What is needed now are pharmaco-economic studies showing that
      personalised management of CD is cost effective. 

PMID- 24037877
TI  - Clusterons as a tool for monitoring populations of tick-borne encephalitis virus.
AB  - Tick-borne encephalitis (TBE) is a natural focal viral neuroinfection that is
      widespread in the temperate zone of Eurasia. Knowledge of the genetic structure
      of tick-borne encephalitis virus (TBEV) populations is important for
      understanding, not only the origin and evolution of the virus, but also the
      formation and maintenance of natural foci. A new approach to the differentiation
      of TBEV strains within subtype, with clusterons as the basis of analysis, has
      recently been proposed. In the present study, the genetic structure of TBEV-Sib
      populations has been investigated based on 387 strains isolated in the Middle
      Urals (Sverdlovsk region). Fourteen of the 18 currently known TBEV-Sib clusterons
      were identified. They belong to the Asian and Eastern European (Baltic) groups.
      It was shown that each TBE foci could be characterized by a unique clusteron
      profile. Three clusterons that emerged within the last 50 years have been
      identified which implies an active evolutionary process in the TBEV-Sib
      populations. The greatest diversity of clusterons was observed in the south of
      the Middle Urals along the Trans-Siberian Way. Such a pattern could reflect the
      history of colonization of the area and is closely related to the roads passing
      from Siberia to the European part of Russia through the Urals. In this article,
      the principles of continuous monitoring in the regional and local TBE foci are
      proposed, based on the quantitative and qualitative analysis of TBEV-Sib
      clusteron profiles.

PMID- 24037880
TI  - 25-Hydroxyvitamin D response to graded vitamin D3 supplementation among obese
      adults.
AB  - CONTEXT: Guidelines have suggested that obese adults need 2 to 3 times more
      vitamin D than lean adults to treat vitamin D deficiency, but few studies have
      evaluated the vitamin D dose response in obese subjects. OBJECTIVE: The purpose
      of this study was to characterize the pharmacokinetics of 25-hydroxyvitamin D
      [25(OH)D] response to 3 different doses of vitamin D3 (cholecalciferol) in a
      group of obese subjects and to quantify the 25(OH)D dose-response relationship.
      DESIGN, SETTING, INTERVENTION, PATIENTS: This was a randomized, single-blind
      study of 3 doses of oral vitamin D3 (1000, 5000, or 10,000 IU) given daily to 67
      obese subjects for 21 weeks during the winter months. MAIN OUTCOME MEASURES:
      Serum 25(OH)D levels were measured at baseline and after vitamin D replacement,
      and 25(OH)D pharmacokinetic parameters were determined, fitting the 25(OH)D
      concentrations to an exponential model. RESULTS: Mean measured increments in
      25(OH)D at week 21 were 12.4 +/- 9.7 ng/mL in the 1000 IU/d group, 27.8 +/- 10.2
      ng/mL in the 5000 IU/d group, and 48.1 +/- 19.6 ng/mL in the 10,000 IU/d group.
      Steady-state increments computed from the model were 20.6 +/- 17.1, 35.2 +/-
      14.6, and 51.3 +/- 22.0 ng/mL, respectively. There were no hypercalcuria or
      hypercalcemia events during the study. CONCLUSION: Our data show that in obese
      people, the 25(OH)D response to vitamin D3 is directly related to dose and body
      size with ~2.5 IU/kg required for every unit increment in 25(OH)D (nanograms per
      milliliter).

PMID- 24037879
TI  - Circulating sclerostin levels and markers of bone turnover in Chinese-American
      and white women.
AB  - CONTEXT: Chinese-American women have bone microarchitectural features that confer
      greater bone stiffness compared to white women, but the physiology underlying
      these findings has not been investigated. OBJECTIVE: The purpose of the study was
      to assess racial differences in serum sclerostin and bone turnover markers
      (BTMs), and to explore their associations with each other, volumetric bone
      mineral density (BMD), and bone microarchitecture in Chinese-American and white
      women. DESIGN AND SETTING: We conducted a cross-sectional study at a university
      hospital. PARTICIPANTS: We studied 138 women. RESULTS: Serum osteocalcin was 19
      28% lower in pre- and postmenopausal Chinese-American vs white women,
      respectively (both P < .01). C-Terminal telopeptide of type I collagen (CTX)
      level was 18-22% lower in pre- and postmenopausal Chinese-American vs white women
      (both P < .05). Pre- vs postmenopausal differences in osteocalcin and CTX were
      greater in white vs Chinese-American women. Sclerostin levels were similar in
      both races, but BTMs were differentially associated with sclerostin by race and
      menopausal status. BTMs were not correlated with sclerostin in Chinese-Americans.
      CTX and bone-specific alkaline phosphatase were positively associated with
      sclerostin (r = 0.353, r = 0.458; both P < .05) in white premenopausal women. In
      contrast, in postmenopausal white women, the associations of sclerostin with
      amino-terminal propeptide of type I procollagen, isoform 5b of tartrate-resistant
      acid phosphatase, and CTX were negative (all P < .05). Adjusting for covariates,
      sclerostin was positively associated with areal BMD in both races. CONCLUSIONS:
      Lower BTMs in Chinese-American women and greater age-related differences in BTMs
      among white women provide a physiological framework to account for racial
      differences in BMD, microarchitecture, and fracture.

PMID- 24037881
TI  - Reduced serum concentrations of carboxylated and undercarboxylated osteocalcin
      are associated with risk of developing type 2 diabetes mellitus in a high
      cardiovascular risk population: a nested case-control study.
AB  - CONTEXT AND OBJECTIVE: Because it has been suggested that osteocalcin (OC), an
      osteoblast-derived hormone, is a new link between bone and glucose metabolism, we
      tested whether serum carboxylated osteocalcin (cOC) and undercarboxylated
      osteocalcin (ucOC) levels are independently associated with the development of
      type 2 diabetes in subjects at high cardiovascular risk. DESIGN, SETTING, AND
      PARTICIPANTS: A prospective, nested case-control study was conducted using data
      from the Prevencion con Dieta Mediterranea (PREDIMED) study. We included 153 case
      subjects with newly diagnosed diabetes and 306 individually matched control
      subjects free of diabetes identified during a mean 5-year follow-up. Conditional
      logistic regression models were used to estimate matched odds ratios for incident
      diabetes according to categories of both forms of OC measured by ELISAs. RESULTS:
      Baseline serum concentrations of both forms of OC were significantly lower in
      case subjects than in control subjects. In subjects with incident cases of
      diabetes, concentrations of cOC, but not of ucOC, were inversely and
      significantly associated with homeostasis model assessment of insulin resistance
      levels (beta = -0.335) and with fasting glucose concentrations (beta = -0.044) in
      control subjects, independent of other relevant confounders. In the conditional
      logistic model that took into account the matching factors, the odds ratios for
      diabetes incidence in the lowest vs the highest tertile of cOC and ucOC were 2.03
      (95% confidence interval, 1.32-3.13) and 1.88 (1.23-2.85), respectively. Further
      adjustment for family history of diabetes, lifestyle, and other confounding
      factors did not appreciably change the magnitude of these associations.
      CONCLUSION: In a population at high cardiovascular risk, low concentrations of
      serum cOC and ucOC were strongly associated with an increased risk of incident
      diabetes.

PMID- 24037882
TI  - a Novel Y152C KCNJ5 mutation responsible for familial hyperaldosteronism type
      III.
AB  - CONTEXT: Primary aldosteronism is a heterogeneous group of disorders comprising
      both sporadic and familial forms. Mutations in the KCNJ5 gene, which encodes the
      inward rectifier K(+) channel 4 (G protein-activated inward rectifier K(+)
      channel 4, Kir3.4), cause familial hyperaldosteronism type III (FH-III) and are
      involved in the pathogenesis of sporadic aldosterone-producing adenomas.
      OBJECTIVE: The objective of the study was to characterize the effects of a newly
      described KCNJ5 mutation in vitro. PATIENTS AND METHODS: The index case is a 62
      year-old woman affected by primary aldosteronism, who underwent left
      adrenalectomy after workup for adrenal adenoma. Exon 1 of KCNJ5 was PCR amplified
      from adrenal tissue and peripheral blood and sequenced. Electrophysiological and
      gene expression studies were performed to establish the functional effects of the
      new mutation on the membrane potential and adrenal cell CYP11B2 expression.
      RESULTS: KCNJ5 sequencing in the index case revealed a new p.Y152C germline
      mutation; interestingly, the phenotype of the patient was milder than most of the
      previously described FH-III families. The tyrosine-to-cysteine substitution
      resulted in pathological Na(+) permeability, cell membrane depolarization, and
      disturbed intracellular Ca(2+) homeostasis, effects similar, albeit smaller, to
      the ones demonstrated for other KCNJ5 mutations. Gene expression studies revealed
      an increased expression of CYP11B2 and its transcriptional regulator NR4A2 in
      HAC15 adrenal cells overexpressing KCNJ5(Y152C) compared to the wild-type
      channel. The effect was clearly Ca(2+)-dependent, because it was abolished by the
      calcium channel blocker nifedipine. CONCLUSIONS: Herein we describe a new
      germline mutation in KCNJ5 responsible for FH-III.

PMID- 24037883
TI  - Diabetes microvascular disease and the risk for bisphosphonate-related
      osteonecrosis of the jaw: a single center study.
AB  - CONTEXT: Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is a severe
      bone disease for which the exact pathogenesis mechanisms are not fully
      understood. OBJECTIVE: The objective of the study is to investigate a possible
      contribution of diabetes and microvascular disease to the pathophysiology of
      BRONJ. DESIGN: We identified 46 patients treated with bisphosphonates who were
      diagnosed with BRONJ based on their medical history during 2009 to 2012 and
      invited them for a dental assessment to confirm the diagnosis. Diabetes diagnosis
      was based on the American Diabetes Association criteria. The study group was
      compared to a control group of 38 patients treated with bisphosphonates without
      evidence of BRONJ. SETTING: The study was conducted at Rambam Health Care Campus,
      a referral center, Haifa, Israel. RESULTS: The results of our study showed that
      of the 46 patients with BRONJ, 31 (67.4%) had diabetes or impaired fasting
      glucose. The proportion with diabetes (37%) was higher than in the control group
      (26.3%; P = .009). The presence of diabetes or impaired fasting glucose increased
      the association with BRONJ by 2.78-fold (confidence interval = 1.27-6.07, P =
      .009). The prevalence of microvascular disease (neuropathy, retinopathy,
      nephropathy) was significantly higher in the BRONJ than in the control group (P =
      .01). The presence of diabetic nephropathy increased the association with BRONJ
      by 3.9-fold (confidence interval = 1.12-13.52, P = .02). CONCLUSIONS: This
      retrospective study suggests an association between diabetes, perhaps mediated
      through microvascular complications, and the development of BRONJ.

PMID- 24037884
TI  - Hypothyroxinemia and TPO-antibody positivity are risk factors for premature
      delivery: the generation R study.
AB  - CONTEXT: Premature delivery is an important risk factor for child mortality and
      psychiatric, metabolic, and cardiovascular disease later in life. In the majority
      of cases, the cause of prematurity cannot be identified. Currently, it remains
      controversial whether abnormal maternal thyroid function during pregnancy
      increases the risk of premature delivery. Therefore, we investigated the relation
      between maternal serum thyroid parameters and the risk of premature delivery in a
      large prospective population-based study. DESIGN: Serum TSH, free T4 (FT4), T4,
      and TPO antibodies (TPOAbs) were determined during early pregnancy in 5971
      pregnant women from the Generation R study. Data were available on maternal age,
      parity, smoking, socioeconomic status, ethnicity, maternal anthropometrics, and
      urinary iodine levels. RESULTS: Of all women, 5.0% had a premature delivery (<37
      weeks), 4.4% had a spontaneous premature delivery, and 1.4% had a very premature
      delivery (<34 weeks). High TSH levels and subclinical hypothyroidism were
      associated with premature delivery but not with spontaneous premature delivery.
      Maternal hypothyroxinemia was associated with a 2.5-fold increased risk of
      premature delivery, a 3.4-fold increased risk of spontaneous premature delivery,
      and a 3.6-fold increased risk of very premature delivery (all P < .01). TPOAb
      positivity was associated with a 1.7-fold increased risk of premature delivery (P
      = .01), a 2.1-fold increased risk of spontaneous premature delivery (P = .02),
      and a 2.5-fold increased risk of very premature delivery (P = .04). These effects
      remained similar after correction for TSH and FT4 levels. CONCLUSIONS:
      Hypothyroxinemia and TPOAb positivity are associated with an increased risk of
      premature delivery. The increased risk in TPOAb-positive women seems to be
      independent of thyroid function.

PMID- 24037885
TI  - Aromatic L-amino acid decarboxylase deficiency is a cause of long-fasting
      hypoglycemia.
AB  - OBJECTIVE/CONTEXT: Long-fasting hypoglycemia in children may be induced by
      neurotransmitter disorders. CASE REPORT: A 5-year-old girl with a medical history
      of chronic diarrhea presented three episodes of severe hypoglycemia (20 mg/dL)
      between ages 3 and 5 years. She became pale and sweaty with hypothermia (33.5
      degrees C), bradycardia (45 bpm), and acidosis and presented a generalized
      seizure. During the 17-hour fast test performed to determine the etiology of her
      hypoglycemia, insulin and C-peptide were appropriately low, and human GH, IGF-I,
      cortisol, amino acids, and acylcarnitines were in the usual range for fasting
      duration. However, the presence of vanillactic and vanilpyruvic acids in urine
      led us to investigate the metabolism of dopamine and serotonin in the
      cerebrospinal fluid. Indeed, these results indicated an aromatic L-amino acid
      decarboxylase deficiency that impairs the synthesis of serotonin, dopamine, and
      catecholamines. The diagnosis was confirmed by the low aromatic L-amino acid
      decarboxylase (AADC) enzyme activity in plasma (5 pmol/min/mL; reference value,
      20-130) and the presence of two heterozygous mutations, c.97G>C (p.V33L,
      inherited from her father) and c.1385G>C (p.R462P, inherited from her mother) in
      the DCC gene. She was supplemented with pyridoxine and raw cornstarch (1 g/kg) at
      evening dinner to reduce the night fast. The episodes of hypoglycemia and the
      chronic diarrhea were suppressed. CONCLUSION: Here is the first case report of
      long-fasting hypoglycemia due to a nontypical AADC deficiency. Hypoglycemia was
      severe, but the other neurological clinical hallmarks present in AADC-deficient
      patients were mild to moderate. Thus, neurotransmitter disorders should be
      considered in any patients presenting hypoglycemia with urine excretion of
      vanillactic acid.

PMID- 24037886
TI  - Recovery of parathyroid hormone secretion and function in postoperative
      hypoparathyroidism: a case series.
AB  - CONTEXT: Transient and permanent postoperative hypoparathyroidism are recognized
      complications of neck surgery. Postoperative hypoparathyroidism is usually
      considered permanent when it persists for 6 months; in rare cases, recovery of
      hypoparathyroidism through 1 year has been described. Recovery of
      hypoparathyroidism years after diagnosis has not previously been reported.
      OBJECTIVE: We report four patients being treated with PTH(1-84) in a research
      protocol who recovered from postoperative hypoparathyroidism many years after
      onset. METHODS: Recovery from hypoparathyroidism was established by: 1) serum
      calcium and PTH levels within the normal range off PTH(1-84) treatment for at
      least 1 week; 2) requirement for daily calcium supplementation reduced to <=1 g;
      and 3) no supplemental active vitamin D therapy. RESULTS: Hypoparathyroidism
      developed in three subjects after repeated neck surgery for primary
      hyperparathyroidism and in one subject after total thyroidectomy for Graves'
      disease. Parathyroid tissue autotransplant was performed in two of the four
      subjects. Two had undetectable PTH levels at study entry, whereas the other two
      subjects had detectable, although low, PTH levels. Hypoparathyroidism had been
      present for at least 8 years, and in one case for 16 years. The recovery of
      parathyroid function followed treatment with PTH(1-84) for 36 to 63 months.
      CONCLUSIONS: Although it remains relatively rare, this report documents recovery
      of long-term postoperative hypoparathyroidism many years after the initial
      diagnosis. A potential role for exogenous PTH is intriguing with several
      plausible mechanisms.

PMID- 24037887
TI  - Overexpression of aromatase associated with loss of heterozygosity of the STK11
      gene accounts for prepubertal gynecomastia in boys with Peutz-Jeghers syndrome.
AB  - CONTEXT: Peutz-Jeghers syndrome (PJS) is an autosomal-dominant disorder that
      arises as a consequence of mutations in the STK11 gene that encodes LKB1. PJS
      males often have estrogen excess manifesting as gynecomastia and advanced bone
      age. We and others have previously described an increase in testicular aromatase
      expression in PJS patients. However, the underlying mechanism has not yet been
      explored. OBJECTIVE: The aim of this study was to characterize the role of LKB1
      in regulating the expression of aromatase in boys with PJS via signaling pathways
      involving AMP-activated protein kinase (AMPK) and cyclic AMP-responsive element
      binding protein-regulated transcription coactivators (CRTCs). PATIENTS: We
      studied testicular biopsies from two boys with STK11 mutations: a 13-year-old boy
      and an unrelated 4-year-old boy with prepubertal gynecomastia and advanced bone
      age, as well as breast tissue from the 13-year-old boy. RESULTS: Loss of
      heterozygosity of STK11, measured by the absence of LKB1 immunofluorescence, was
      observed in Sertoli cells of abnormal cords of testis samples from affected
      individuals. This was associated with loss of p21 expression and decreased
      phosphorylation of AMPK, known downstream targets of LKB1, as well as the
      increased expression of aromatase. Similar results of low LKB1 expression in
      cells expressing aromatase were observed in the mammary epithelium from one of
      these individuals. Nuclear expression of the CRTC proteins, potent stimulators of
      aromatase and known to be inhibited by AMPK, was significantly correlated with
      aromatase. CONCLUSIONS: Loss of heterozygosity of the STK11 gene leads to an
      increase in aromatase expression associated with an increase in CRTC nuclear
      localization, thereby providing a mechanism whereby PJS results in increased
      endogenous estrogens in affected males.

PMID- 24037888
TI  - PCAF impairs endometrial receptivity and embryo implantation by down-regulating
      beta3-integrin expression via HOXA10 acetylation.
AB  - BACKGROUND: Homeobox A10 (HOXA10), a key transcription factor, plays a critical
      role in endometrial receptivity by regulating the expression of downstream target
      genes, such as beta3-integrin (ITGB3), but little is understood about the
      mechanisms of the posttranslational modification of HOXA10 during embryo
      implantation. OBJECTIVE: The aim of this study was to assess the effect of HOXA10
      acetylation by p300/CREB-binding protein-associated factor (PCAF) in the embryo
      implantation process. METHODS: The association of HOXA10 with PCAF was detected
      by coimmunoprecipitation, Western blotting, and confocal immunofluorescent
      assays. A luciferase reporter assay, Western blotting, quantitative real-time
      PCR, and chromatin immunoprecipitation techniques were used to determine the
      effect of PCAF on HOXA10 protein stability and the HOXA10-mediated regulation of
      ITGB3 expression. HOXA10-PCAF association on embryo implantation was evaluated
      using a BeWo spheroid attachment assay. PCAF expression in the eutopic
      endometrium of women with endometriosis and fertile controls was measured by
      Western blotting technique. RESULTS: PCAF was identified as an HOXA10-interacting
      protein and inhibited HOXA10-mediated ITGB3 transcription via acetylating HOXA10
      at K338 and K339. Overexpressing or knocking down PCAF in Ishikawa cells showed
      that PCAF not only down-regulated HOXA10-mediated ITGB3 protein expression but
      also diminished HOXA10-mediated embryo adhesiveness by acetylating HOXA10 (P <
      .05). Furthermore, we found aberrantly high PCAF expression in the eutopic
      endometrium of women with a diagnosis of endometriosis compared with the fertile
      controls (P < .05). CONCLUSIONS: These observations demonstrate that 1) HOXA10
      associates with and is acetylated by PCAF at lysines K338 and K339 in Ishikawa
      cells and 2) HOXA10-PCAF association impairs embryo implantation by inhibiting
      ITGB3 protein expression in endometrial epithelial cells.

PMID- 24037889
TI  - Effects of polycystic ovary syndrome (PCOS), sex hormones, and obesity on
      circulating miRNA-21, miRNA-27b, miRNA-103, and miRNA-155 expression.
AB  - CONTEXT: MicroRNAs (miRNAs) are small, noncoding RNA sequences that negatively
      regulate gene expression at the post-transcriptional level. miRNA-21, miRNA-27b,
      miRNA-103, and miRNA-155 have been associated with metabolic disorders such as
      obesity and diabetes, which are also associated with polycystic ovary syndrome
      (PCOS). OBJECTIVE: We aimed to evaluate the effects of sex, sex hormones, and
      PCOS and their interactions with obesity on the expression in the circulation of
      these miRNAs. DESIGN: This was a case-control study. SETTINGS: The setting was an
      academic hospital. PARTICIPANTS: We included 12 control women, 12 patients with
      PCOS, and 12 men selected as to have similar body mass index (BMI) and age. Six
      subjects per group had normal weight (BMI < 25 kg/m(2)), and six subjects per
      group were obese (BMI >= 30 kg/m(2)). INTERVENTIONS: Blood samples were collected
      early in the morning after a 12-hour fast. MAIN OUTCOME MEASURES: We measured
      whole blood expression of miRNA-21, miRNA-27b, miRNA-103, and miRNA-155. RESULTS:
      Obesity significantly reduced the expression of miRNA-21, miRNA-27b, and miRNA
      103. However, there was a significant interaction between obesity and the group
      of subjects in the expression of miRNA-21, miRNA-27b, miRNA-103, and miRNA-155
      consisting of obesity reducing the expression of these miRNAs in control woman
      and men, but tending to increase their expression in women with PCOS. These
      differences paralleled those observed in serum T concentrations. CONCLUSIONS: The
      present results suggest that miRNAs that play an important role in metabolic and
      immune system processes are influenced by obesity and circulating androgen
      concentrations.

PMID- 24037890
TI  - Trial of recombinant follicle-stimulating hormone pretreatment for GnRH-induced
      fertility in patients with congenital hypogonadotropic hypogonadism.
AB  - CONTEXT AND OBJECTIVE: The optimal strategy for inducing fertility in men with
      congenital hypogonadotropic hypogonadism (CHH) is equivocal. Albeit a
      biologically plausible approach, pretreatment with recombinant FSH (rFSH) before
      GnRH/human chorionic gonadotropin administration has not been sufficiently
      assessed. The objective of the study was to test this method. DESIGN AND SETTING:
      This was a randomized, open-label treatment protocol at an academic medical
      center. PATIENTS AND INTERVENTIONS: GnRH-deficient men (CHH) with prepubertal
      testes (<4 mL), no cryptorchidism, and no prior gonadotropin therapy were
      randomly assigned to either 24 months of pulsatile GnRH therapy alone (inducing
      endogenous LH and FSH release) or 4 months of rFSH pretreatment followed by 24
      months of GnRH therapy. Patients underwent serial testicular biopsies, ultrasound
      assessments of testicular volume, serum hormone measurements, and seminal fluid
      analyses. RESULTS: rFSH treatment increased inhibin B levels into the normal
      range (from 29 +/- 9 to 107 +/- 41 pg/mL, P < .05) and doubled testicular volume
      (from 1.1 +/- 0.2 to 2.2 +/- 0.3 mL, P < .005). Histological analysis showed
      proliferation of both Sertoli cells (SCs) and spermatogonia, a decreased SC to
      germ cell ratio (from 0.74 to 0.35), and SC cytoskeletal rearrangements. With
      pulsatile GnRH, the groups had similar hormonal responses and exhibited
      significant testicular growth. All men receiving rFSH pretreatment developed
      sperm in their ejaculate (7 of 7 vs 4 of 6 in the GnRH-only group) and showed
      trends toward higher maximal sperm counts. CONCLUSIONS: rFSH pretreatment
      followed by GnRH is successful in inducing testicular growth and fertility in men
      with CHH with prepubertal testes. rFSH not only appears to maximize the SC
      population but also induces morphologic changes, suggesting broader developmental
      roles.

PMID- 24037891
TI  - Stimulated thyroglobulin at recombinant human TSH-aided ablation predicts disease
      free status one year later.
AB  - CONTEXT: Thyroglobulin (Tg) levels measured at the time of remnant ablation after
      thyroid hormone withdrawal (THW) were shown to have prognostic value in
      predicting disease-free status. OBJECTIVES: Our objectives were to determine
      whether stimulated Tg levels, measured at the time of remnant ablation performed
      under recombinant human TSH (rhTSH) stimulation, has value in predicting absence
      of detectable disease 1 year after radioiodine therapy and to compare the results
      obtained with this approach with a cohort of patients submitted to ablation after
      THW. DESIGN: This was a prospective observational study. SETTING AND PATIENTS:
      The study included 293 consecutive patients treated for a differentiated thyroid
      carcinoma with no initial evidence of distant metastasis. All patients were
      submitted to a total or near-total thyroidectomy, followed by ablation either
      under rhTSH (n = 151) or endogenous TSH stimulation (n = 142). Patients with
      positive Tg antibodies were excluded. MAIN OUTCOME MEASURES: The predictive value
      of Tg at ablation was assessed by receiver operating characteristic curve
      analysis. RESULTS: In the rhTSH group, 96 patients (73.3%) were considered
      disease-free at 1 year. Stimulated Tg at ablation after rhTSH was found to be an
      independent prognostic indicator of disease persistence 12 months later. The
      highest-accuracy cutoff value for absence of detectable disease was defined as
      7.2 ng/mL, with a negative predictive value of 90%. In the THW group, Tg at
      ablation also proved to have independent predictive value. Using the same
      threshold (7.2 ng/mL), the negative predictive value of Tg was 95% in the THW
      group. CONCLUSIONS: When rhTSH was used, stimulated Tg at ablation had
      independent predictive value for disease-free status 1 year later. A low
      stimulated Tg at rhTSH-aided ablation may be considered a favorable prognosis
      factor.

PMID- 24037892
TI  - Associations between ethnicity, body composition, and bone mineral density in a
      Southeast Asian population.
AB  - CONTEXT AND OBJECTIVE: Chinese men in Singapore have a higher incidence of hip
      fractures than Malay and Indian men. We investigated whether there were
      corresponding ethnic differences in peak bone mineral density (BMD) in young men
      and whether differences in body composition influenced peak BMD. DESIGN AND
      SETTING: This was a cross-sectional study of healthy volunteers in a tertiary
      medical center. PARTICIPANTS: A total of 100 Chinese, 82 Malay, and 80 Indian men
      aged 21 to 40 years, with body mass index between 18 and 30 kg/m(2) underwent
      dual-energy x-ray absorptiometry to assess BMD, lean mass (LM) and fat mass (FM),
      and magnetic resonance imaging to quantify abdominal subcutaneous and visceral
      adipose tissue. Multiple linear regression models, with adjustment for age and
      height (as a proxy for skeletal size), were used. RESULTS: Malay and Indian men
      had significantly higher BMD than Chinese men at the lumbar spine (Malay: B, 0.06
      +/- 0.02, P = .001; Indian: B, 0.03 +/- 0.02, P = .049), femoral neck (Malay: B
      0.04 +/- 0.02, P = .034; Indian: B, 0.04 +/- 0.02, P = .041), hip (Malay: B, 0.05
      +/- 0.02, P = .016; Indian: B, 0.06 +/- 0.02, P = .001), and ultradistal radius
      (Malay: B, 0.03 +/- 0.01, P < .001; Indian: B, 0.02 +/- 0.01, P = .029), and this
      difference was retained after adjustment for LM and FM, except in Malay men at
      the femoral neck and in Indian men at the ultradistal radius. LM was an important
      independent determinant of BMD at all sites, whereas FM, subcutaneous adipose
      tissue, and visceral adipose tissue were not significantly associated with BMD at
      any site. CONCLUSIONS: Lower peak BMD in Chinese men may partly explain the
      higher fracture incidence in this ethnic group. Further studies are needed to
      elucidate the reasons for these ethnic differences in bone accumulation.

PMID- 24037893
TI  - Neoadjuvant chemotherapy followed by concurrent chemoradiation for locoregionally
      advanced nasopharyngeal carcinoma: interim results from 2 prospective phase 2
      clinical trials.
AB  - BACKGROUND: The authors studied the efficacy of neoadjuvant chemotherapy,
      consisting of a taxane, cisplatin, and 5-fluorouracil (5-FU) (the TPF regimen)
      followed by concurrent chemoradiation, in 2 separately designed and synchronously
      executed phase 2 trials for stage III and IVA/IVB nasopharyngeal cancer (NPC).
      METHODS: Patients with newly diagnosed NPC were accrued to 2 trials, 1 for
      patients with stage III disease and the other for patients with IVA/IVB disease.
      All patients received TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), and 5-FU
      2500 mg/m(2) every 3 weeks for 3 cycles) followed by cisplatin 40 mg/m(2) per
      week concurrently with either 3-dimensional conformal radiation therapy or
      intensity-modulated radiation therapy. RESULTS: From January 2007 to July 2011,
      52 eligible patients with stage III NPC and 64 eligible patients with
      nonmetastatic stage IV NPC were accrued. With a median follow-up of 32.9 months,
      the 3-year overall survival rates were 94.8% (95% confidence interval [CI], 87.6%
      100%) and 90.2% (95% CI, 81.8%-98.6%) for the stage III NPC group and the IVA/IVB
      NPC group, respectively. The 3-year progression-free survival, distant metastasis
      free survival, and local progression-free survival rates were 78.2% (95% CI,
      64.6%-91.8%), 90.5% (95% CI, 79.7%-100%), and 93.9%(87.1%-100%), respectively,
      for patients with stage III NPC and 85.1% (95% CI, 75.1%-95.1%), 88% (95% CI,
      78.6%-97.4%), and 100%, respectively, for patients with stage IVA/IVB NPC. The
      most common severe (grade 3/4) hematologic and nonhematologic adverse events were
      neutropenia (64 patients; 55.2%) and nausea/vomiting (23 patients; 19.8%).
      CONCLUSIONS: Neoadjuvant TPF followed by concurrent chemoradiation was well
      tolerated and produced encouraging outcomes in patients with locally advanced NPC
      in this hypothesis-generating study. The authors concluded that randomized
      controlled trials are warranted to definitively confirm this aggressive and
      potentially efficacious strategy.

PMID- 24037895
TI  - Ductular reaction in hereditary hemochromatosis: the link between hepatocyte
      senescence and fibrosis progression.
AB  - The development of portal fibrosis following the iron loading of hepatocytes is
      the first stage of fibrogenesis in hereditary hemochromatosis. In other chronic
      liver diseases it has been shown that a ductular reaction (DR) appears early,
      correlates with fibrosis progression, and is a consequence of activation of an
      alternative pathway of hepatocyte replication. This study was designed to
      investigate the presence of the DR in hemochromatosis and describe its
      associations. Liver biopsies from 63 C282Y homozygous patients were assessed for
      hepatic iron concentration (HIC) and graded for iron loading, fibrosis stage,
      steatosis, and inflammation. Immunostaining allowed quantification of the DR,
      hepatocyte senescence and proliferation, and analysis incorporated clinical data.
      Hepatocyte senescence was positively correlated with HIC, serum ferritin, and
      oxidative stress. A DR was demonstrated and occurred prior to histological
      fibrosis. HIC, age, hepatocyte senescence and proliferation, portal inflammation,
      and excessive alcohol consumption all had significant associations with the
      extent of the DR. In multivariate analysis, iron loading, hepatocyte replicative
      arrest, and portal inflammation remained independently and significantly
      associated with the DR. Of factors associated with fibrosis progression, the DR
      (odds ratio [OR] 10.86 P<0.0001) and the presence of portal inflammation (OR
      4.31, P=0.028) remained significant after adjustment for cofactors. The extent of
      the DR regressed following therapeutic venesection. CONCLUSION: Iron loading of
      hepatocytes leads to impaired replication, stimulating the development of the DR
      in hemochromatosis and this correlates strongly with hepatic fibrosis. Portal
      inflammation occurs in hemochromatosis and is independently associated with the
      DR and fibrosis, and thus its role in this disease should be evaluated further.

PMID- 24037894
TI  - Most patients with cancer-associated dermatomyositis have antibodies to nuclear
      matrix protein NXP-2 or transcription intermediary factor 1gamma.
AB  - OBJECTIVE: Since dermatomyositis (DM) is associated with an increased risk of
      malignancy, accurate identification of patients likely to harbor cancers is
      important. Using immunoprecipitations from radiolabeled cell lysates, several
      groups recently showed that anti-transcription intermediary factor 1gamma (anti
      TIF-1gamma) antibodies are associated with malignancy in DM. We undertook this
      study to develop sensitive, specific assays to detect antibodies against TIF
      1gamma and nuclear matrix protein NXP-2 and to evaluate their association with
      malignancy in DM. METHODS: To detect anti-TIF-1gamma antibodies,
      immunoprecipitations were performed using lysates made from HeLa cells
      overexpressing TIF-1gamma, with detection by immunoblotting. Anti-NXP-2
      antibodies were assayed by immunoprecipitation using (35) S-methionine-labeled
      NXP-2 generated by in vitro transcription/translation. We analyzed patient sera
      from DM cohorts seen at the Stanford University Dermatology Clinic (n = 111) and
      the Johns Hopkins Myositis Center (n = 102). RESULTS: A total of 17% and 38% of
      patients had antibodies against NXP-2 and TIF-1gamma, respectively. Reactivity
      against either NXP-2 or TIF-1gamma identified 83% of patients with cancer
      associated DM. In addition to older age and male sex, cancer was associated with
      antibodies to NXP-2 or TIF-1gamma on multivariate analysis (odds ratio 3.78 [95%
      confidence interval 1.33-10.8]). Stratification by sex revealed that anti-NXP-2
      was specifically associated with cancer in males (odds ratio 5.78 [95% confidence
      interval 1.35-24.7]). CONCLUSION: These studies demonstrate that anti-NXP-2 and
      anti-TIF-1gamma antibodies are frequent DM specificities (found in 55% of
      patients) and are present in most patients with cancer-associated DM.

PMID- 24037896
TI  - Combination of E2F-1 promoter-regulated oncolytic adenovirus and cytokine-induced
      killer cells enhances the antitumor effects in an orthotopic rectal cancer model.
AB  - Due to the anatomical structure of the rectum, the treatment of rectal cancer
      remains challenging. Ad-E2F, an oncolytic adenovirus containing the E2F-1
      promoter, can selectively replicate within and kill cancer cells derived from
      solid tumors. Thus, this virus provides a novel approach for the treatment of
      rectal cancer. Given the poor efficacy and possible adverse reactions that arise
      from the use of oncolytic virus alone and the results of our analysis of the
      efficacy of Ad-E2F in the treatment of rectal cancer, we investigated the use of
      oncolytic adenovirus in combination with adoptive immunotherapy using cytokine
      induced killer (CIK) cells as a therapeutic treatment for rectal cancer. Our
      results illustrated that E2F-1 gene expression is higher in rectal cancer tissue
      than in normal tissue. Furthermore, the designed oncolytic adenovirus Ad-E2F is
      capable of selectively killing colorectal cell lines but has no significant
      effect on CIK cells. The results of in vitro and in vivo experiments demonstrated
      that combined therapy with Ad-E2F and CIK cells produce stronger antitumor
      effects than the administration of Ad-E2F or CIK cells alone. For low rectal
      cancers that are suitable for intratumoral injection, local injections of
      oncolytic viruses in combination with CIK cell-based adoptive immunotherapy may
      be suitable as a novel comprehensive therapeutic approach.

PMID- 24037897
TI  - Capillary electrophoresis in the diagnosis of surgical site infections.
AB  - A surgical site infection (SSI) is an infection that occurs after surgery in the
      part of the body where the surgery took place. A SSI may range from a
      spontaneously limited wound discharge within 7-10 days of an operation to a life
      threatening postoperative complication, such as a sternal infection after open
      heart surgery. Most surgical site infections are caused by contamination of an
      incision with microorganisms from the patient's own body during surgery. From the
      analytical point of view the complex natures of these samples as well as the low
      concentrations of analytes require a system with high sensitivity and efficiency.
      Such situation require a technique such as capillary electrophoresis which is a
      powerful and versatile separation technique that promises to rival high
      performance liquid chromatography when applied to the separation of both charged
      and neutral species. During the study, it has been demonstrated that CZE
      identifying characteristics of such groups of pathogens such as bacteria G (+)
      and different species of bacteria G (-) and also develop weekly individual
      profiles for patients after application of antibiotics. This was done in order to
      show the impact of antibiotic therapy in change "numbers" of bacteria present in
      the wound after surgery. The method proved to be the ideal straight specificity
      in the case of E. coli (100%). Finally analysis of the spectra and the second
      derivatives of the UV-Vis spectra confirmed the similarity in the profiles and
      showed that the CZE is a great method for fast screening test in bacterial
      infection.

PMID- 24037898
TI  - alpha1-Syntrophin-deficient mice exhibit impaired muscle force recovery after
      osmotic shock.
AB  - INTRODUCTION: alpha1-syntrophin, a member of the dystrophin complex, recruits
      membrane molecules, including aquaporin-4, at the sarcolemma. The physiological
      functions of alpha1-syntrophin are poorly understood. METHODS: We examined the
      physiological characteristics of alpha1-syntrophin-deficient muscles under
      osmotic stress conditions to test the possibility that mutant muscles are less
      tolerant of osmotic shock. RESULTS: Isolated muscle bundles from mutant mice
      showed markedly reduced force production after hypo-osmotic shock. In addition,
      the mutant muscle bundles showed delayed recovery of specific gravity after being
      exposed to hypo-osmotic conditions. Two consecutive exercise tests on the
      treadmill revealed their performance in the second test was significantly lower
      than for wild-type mice. Furthermore, mutant mice had higher serum lactate
      concentrations after treadmill exercise. CONCLUSIONS: Although the lack of alpha1
      syntrophin from the sarcolemma does not lead to muscle degeneration, our results
      suggest that it may be partly involved in the pathophysiology of dystrophin
      deficient Duchenne muscular dystrophy.

PMID- 24037899
TI  - A child of the empire: British sociology and colonialism, 1940s-1960s.
AB  - British sociology was established as an academic discipline between 1945 and
      1965, just as the British Empire was gearing up for a new phase of developmental
      colonialism backed by the social and other sciences. Many parts of the emerging
      sociological discipline became entangled with colonialism. Key themes and methods
      in sociology and the staff of sociology departments emerged from this colonial
      context. Historians have tended to place postwar British sociology in the context
      of expanding higher education and the welfare state, and have overlooked this
      colonial constellation. The article reconstructs this forgotten moment of
      disciplinary founding and explores three of the factors that promoted colonial
      sociology: the Colonial Social Science Research Council, the so-called Asquith
      universities, and the social research institutes in the colonies; and the
      involvement of sociologists from the London School of Economics in training
      colonial officials. 

PMID- 24037900
TI  - The role of natural and UV-induced skin pigmentation on low-fluence IPL-induced
      side effects: a randomized controlled trial.
AB  - BACKGROUND AND OBJECTIVES: The risk of adverse skin effects following light-based
      hair removal is greater in pigmented skin based on the theory of selective
      photothermolysis. Thus sunlight-induced pigment i.e., facultative pigmentation,
      increases the risk of adverse skin effects, perhaps disproportionately. The aim
      of this study was to evaluate the influence of constitutive and facultative skin
      pigmentation on low-fluence intense pulsed light (IPL)-induced adverse skin
      effects. STUDY DESIGN/MATERIALS AND METHODS: Twenty-one subjects with Fitzpatrick
      skin type II-IV were enrolled. Two buttock blocks were randomized to receive 0 or
      8 solar simulated ultraviolet radiation (UVR) exposures of consecutively
      increasing Standard Erythema Doses (2-4 SED). Each block was subdivided into four
      sites, randomized to receive IPL of 0, 7, 8, or 10 J/cm(2) , once a week for 3
      weeks. Biopsies were taken 16-24 hours after the first IPL exposure and subjects
      were seen 1 and 4 weeks after the last IPL exposure. Outcome measures were: (i)
      skin reactions, (ii) pain, (iii) mRNA expression of pigment-markers
      microphthalmia-associated transcription factor (MITF) and pro-opiomelanocortin
      (POMC), and (iv) clinical appearance of biopsy wounds. RESULTS: Skin pigmentation
      increased after UVR (baseline median 13.8%, after UVR 28.1%, P = 0.0001) in all
      skin types. Subjects reported low pain intensities (median 1.5, scale 0-10) and
      experienced transient erythema immediately after IPL exposure. No persistent
      erythema, blisters, crusting, textual, or pigment changes were observed. The risk
      of erythema and pain intensities increased with IPL dose and skin pigmentation (P
      < 0.03). There was no difference in pain or skin reactions in skin with similar
      degree of natural and facultative pigmentation (P >= 0.104). Expression of
      cellular pigment-markers was not influenced by IPL exposure, neither in
      constitutive nor in facultative pigmented skin. Clinical appearance of biopsy
      wounds was unaffected by IPL exposure. CONCLUSION: The prevalence and intensity
      of low-fluence IPL-induced adverse skin effects depended on IPL dose and skin
      pigmentation regardless of the origin, i.e., constitutive versus UV induced.

PMID- 24037901
TI  - A study of embryonic stem cell-related proteins in human astrocytomas:
      identification of Nanog as a predictor of survival.
AB  - Recent studies suggest that the regulatory networks controlling the functions of
      stem cells during development may be abnormally active in human cancers. An
      embryonic stem cell (ESC) gene signature was found to correlate with a more
      undifferentiated phenotype of several human cancer types including gliomas, and
      associated with poor prognosis in breast cancer. In the present study, we used
      tissue microarrays of 80 low-grade (WHO Grade II) and 98 high-grade human gliomas
      (WHO Grades III and IV) to investigate the presence of the ESC-related proteins
      Nanog, Klf4, Oct4, Sox2 and c-Myc by immunohistochemistry. While similar patterns
      of co-expressed proteins between low- and high-grade gliomas were present, we
      found up-regulated protein levels of Nanog, Klf4, Oct4 and Sox2 in high-grade
      gliomas. Survival analysis by Kaplan-Meier analysis revealed a significant
      shorter survival in the subgroups of low-grade astrocytomas (n = 42) with high
      levels of Nanog protein (p = 0.0067) and of Klf4 protein (p = 0.0368), in high
      grade astrocytomas (n = 85) with high levels of Nanog (p = 0.0042), Klf4 (p =
      0.0447), and c-Myc (p = 0.0078) and in glioblastomas only (n = 71) with high
      levels of Nanog (p = 0.0422) and of c-Myc (p = 0.0256). In the multivariate
      model, Nanog was identified as an independent prognostic factor in the subgroups
      of low-grade astrocytomas (p = 0.0039), high-grade astrocytomas (p = 0.0124) and
      glioblastomas only (p = 0.0544), together with established clinical variables in
      these tumors. These findings provide further evidence for the joint regulatory
      pathways of ESC-related proteins in gliomas and identify Nanog as one of the key
      players in determining clinical outcome of human astrocytomas. 

PMID- 24037902
TI  - The genetics of dilated cardiomyopathy: a prioritized candidate gene study of
      LMNA, TNNT2, TCAP, and PLN.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM), which is characterized by left
      ventricular enlargement and systolic dysfunction, is divided into cases with a
      clear predisposing condition (eg, hypothyroidism, chemotherapeutic agents,
      alcoholism, ischemia) and those of unknown cause (idiopathic DCM). Many cases
      (20%-35%) of DCM are familial, implicating a genetic contribution to the
      etiology. More than 30 genes have been identified, many involving "private"
      mutations not shared among families. Evidence suggests that nonfamilial cases
      also have a genetic predisposition, again involving many genes. The goal of this
      study was to identify mutations in genes associated with DCM in a Quebec study
      sample including familial and nonfamilial DCM cases. HYPOTHESIS: A prioritized
      gene study conducted within a framework for the classification of identified
      genetic variants could yield etiological information even in the absence of
      family data. METHODS: We sequenced 4 previously identified genes: lamin A/C
      (LMNA), cardiac troponin T type 2 (TNNT2), titin-cap (TCAP), and phospholamban
      (PLN). RESULTS: We discovered a nonsense mutation in the LMNA gene and a
      frameshift mutation in the TNNT2 gene, as well as other clinically significant
      variants that were not observed in publicly available databases or in Quebec
      based controls. PLN was sequenced to investigate a previously published promoter
      variant. However, our data confirm that this variant does not have a causal role
      in DCM. CONCLUSIONS: Despite high locus and allele heterogeneity, we demonstrate
      that a prioritized gene study, combined with next-generation exome-sequencing
      data, can be fruitful for the identification of DCM mutations.

PMID- 24037903
TI  - Prevalence of ventilation blockages in patients affected by attic pathology: a
      case-control study.
AB  - OBJECTIVES/HYPOTHESIS: Using a retrospective video evaluation of exclusive
      endoscopic middle ear procedures, we analyzed the different anatomical and
      pathological findings between patients with attic disease or cholesteatoma and
      patients without attic disease. STUDY DESIGN: A case-control study based on a
      retrospective chart review in a tertiary university referral center. METHODS:
      Videos from endoscopic middle ear procedures carried out between February 2007
      and August 2012 were reviewed. We analyzed and compared two groups of patients
      who underwent surgery in our university hospital: patients with selective attic
      disease (e.g., non-self-cleaning attic selective retraction pockets or attic
      cholesteatoma) were compared with subjects without attic disease (e.g., chronic
      middle ear disease, congenital cholesteatoma, or secondary cholesteatoma).
      RESULTS: In total, 152 patients were included in the study. Of these, 102 were
      affected by primary acquired cholesteatoma (84/102) or severe pars flaccida
      retraction pockets (18/102), whereas 50 cases were controls. A blockage of the
      isthmus was present in almost all cases (98/102) compared with a lower prevalence
      in controls (3/50) (P < .0001). Similarly, a complete tensor fold was identified
      in 99/102 patients compared to controls (9/46; data were not available in four
      controls) (P = .001). CONCLUSIONS: Selective epitympanic dysventilation occurred
      when a blockage of the isthmus was present and associated with a complete tensor
      fold, causing ventilatory separation between the epitympanum and mesotympanum.
      This mechanism could be the basis for a selective decrease in pressure in the
      attic, with the subsequent development of attic retraction pockets and
      cholesteatoma even in subjects with a normally functioning eustachian tube.

PMID- 24037904
TI  - Flavonoid-metal ion complexes: a novel class of therapeutic agents.
AB  - Flavonoids are among the most investigated phytochemicals due to their
      pharmacological and therapeutic activities. Their ability to chelate with metal
      ions has resulted in the emergence of a new category of molecules with a broader
      spectrum of pharmacological activities. However, the biological significance of
      these flavonoid-metal ion complexes is yet to be completely explored. Moreover,
      no concerted efforts have been made to elucidate their molecular targets and
      mechanisms of action. This review attempts to provide a snapshot of the various
      biological activities reported for flavonoid-metal ion complexes and their
      potential as therapeutic agents. Understanding the mechanism of action and the
      influence of structure will provide a strong basis to design novel flavonoid
      metal ion complexes of therapeutic significance.

PMID- 24037905
TI  - Genotypic variability for antioxidant and quality parameters among tomato
      cultivars, hybrids, cherry tomatoes and wild species.
AB  - BACKGROUND: Wide germplasm diversity and transferability of antioxidant
      parameters is the primary requirement for the development of high-antioxidant
      tomato cultivars. The present study was conducted to screen tomato genotypes
      including hybrids, varieties, cherry tomatoes, wild species, elite germplasm
      lines, interspecific hybrids and backcross populations for antioxidant activity
      and other quality parameters to select high-antioxidant lines with good total
      soluble solids (TSS) for further usage in crop improvement programmes. RESULTS:
      Wild species and interspecific hybrids between LA-1777 (Solanum habrochaites) and
      an elite genotype 15SBSB recorded very high antioxidant capacity (FRAP), DPPH
      radical-scavenging ability, and high phenols and flavonoids. Interspecific
      hybrids also recorded very high total soluble solids (TSS). Significantly higher
      total carotenoids, lycopene and vitamin C were observed in IIHR-249-1 with
      moderately higher TSS. Cherry tomato lines IIHR-2866, 2865 and 2864 recorded four
      to five times more beta-carotene than commercial hybrids/varieties. CONCLUSION:
      Tomato line IIHR-249-1 can be used for improving antioxidant capacity, total
      carotenoids and lycopene in tomato breeding programmes. Cherry tomato lines IIHR
      2866, 2865 and 2864 can be used for improving beta-carotene content. LA-1777 and
      interspecific hybrids could be used for developing tomato lines rich in
      antioxidants as well as TSS.

PMID- 24037907
TI  - Temperature-induced conformational transition of bovine serum albumin in neutral
      aqueous solution by reversed-phase liquid chromatography.
AB  - The temperature-induced conformational transition of bovine serum albumin (BSA)
      in neutral aqueous solution was studied using intrinsic fluorescence emission
      spectrum, reversed-phase liquid chromatography and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and the conformation transition thermodynamic
      parameters were determined in the temperature range 12-50  degrees C. The results
      showed that, in the temperature range 12-20  degrees C, BSA only existed in a
      single conformation state A, while in the temperature range 22-50  degrees C, it
      existed in two different conformation states: A and B. The percentage of
      conformation state A decreased while that of conformation state B increased with
      the increase in temperatures, and when temperature approached 50  degrees C
      conformation state B accounted for approximately 25% of all conformation states
      of BSA. In the conformational transition of BSA from conformation state A to
      conformation state B, the positive enthalpy change, entropy change and free
      energy changes demonstrated that the conformational transition was endothermic,
      nonspontaneous and mainly entropy-driven.

PMID- 24037906
TI  - An investigation on the relationship between the occurrence of CMV DNAemia and
      the development of invasive aspergillosis in the allogeneic stem cell
      transplantation setting.
AB  - Cytomegalovirus (CMV) infection might increase the risk of fungal superinfection
      in allogeneic stem cell transplant patients. The potential association between
      the occurrence of CMV DNAemia and the development of invasive aspergillosis in
      this clinical setting was investigated. The current retrospective observational
      study included 167 patients undergoing T cell-replete allogeneic stem cell
      transplantation. Virological monitoring of active CMV infection was performed by
      the pp65 antigenemia assay and/or by a plasma real-time PCR assay. A total of 109
      out of 167 patients developed CMV DNAemia. Twenty-three patients had proven (n =
      4) or probable (n = 19) invasive aspergillosis. The occurrence of CMV DNAemia was
      not significantly associated with the subsequent development of invasive
      aspergillosis (P = 0.38). Overall, the duration of the episodes of active CMV
      infection and the peak level of CMV DNAemia within the episodes were comparable,
      irrespective of whether invasive aspergillosis developed subsequently or not (P =
      0.99; P = 0.70, respectively). Peak CMV DNA load in patients with proven or
      probable invasive aspergillosis who died was higher (median, 5,461 copies/ml)
      than that in those who survived (median 1,179 copies/ml) (P = 0.41). The data
      argue against the existence of an association between the occurrence of CMV
      DNAemia and the development of invasive aspergillosis, however, CMV replication,
      particularly at high levels, might aggravate the prognosis of this disease.

PMID- 24037910
TI  - Indirect estimates of natal dispersal distance from genetic data in a stream
      dwelling fish (Mogurnda adspersa).
AB  - Recent work has highlighted the need to account for hierarchical patterns of
      genetic structure when estimating evolutionary and ecological parameters of
      interest. This caution is particularly relevant to studies of riverine organisms,
      where hierarchical structure appears to be commonplace. Here, we indirectly
      estimate dispersal distance in a hierarchically structured freshwater fish,
      Mogurnda adspersa. Microsatellite and mitochondrial DNA (mtDNA) data were
      obtained for 443 individuals across 27 sites separated by an average of 1.3 km
      within creeks of southeastern Queensland, Australia. Significant genetic
      structure was found among sites (mtDNA Phi(ST) = 0.508; microsatellite F(ST) =
      0.225, F'(ST) = 0.340). Various clustering methods produced congruent patterns of
      hierarchical structure reflecting stream architecture. Partial mantel tests
      identified contiguous sets of sample sites where isolation by distance (IBD)
      explained F(ST) variation without significant contribution of hierarchical
      structure. Analysis of mean natal dispersal distance (sigma) within sets of IBD
      linked sample sites suggested most dispersal occurs over less than 1 km, and the
      average effective density (D(e)) was estimated at 11.5 individuals km(-1);
      indicating sedentary behavior and small effective population size are responsible
      for the remarkable patterns of genetic structure observed. Our results
      demonstrate that Rousset's regression-based method is applicable to estimating
      the scale of dispersal in riverine organisms and that identifying contiguous
      populations that satisfy the assumptions of this model is achievable with genetic
      clustering methods and partial correlations.

PMID- 24037911
TI  - Isoniazid hepatotoxicity: progress in understanding the immunologic component.

PMID- 24037912
TI  - Association between p53 Arg72Pro polymorphism and thyroid cancer risk: a meta
      analysis.
AB  - The p53 is a tumor suppressor gene which may be involved in the development of
      thyroid cancer. Studies investigating the association between p53 Arg72Pro
      polymorphism and thyroid cancer risk reported conflicting results. The aim of the
      meta-analysis was to derive a more precise assessment of the association between
      p53 Arg72Pro polymorphism and thyroid cancer risk. A literature search of PubMed
      and Web of Science from their inception through March 2013 was conducted. Odds
      ratios (OR) with 95% confidence intervals (95% CI) were used to assess the
      strength of the association. Eight case-control studies were included with a
      total of 874 thyroid cancer cases and 1,891 controls. The meta-analysis results
      showed that the p53 Arg72Pro polymorphism was only associated with thyroid cancer
      risk under the recessive model (ProPro vs. ArgArg/ArgPro: OR = 1.83, 95% CI 1.05
      3.20, P = 0.034). However, there was no significant association between p53
      Arg72Pro polymorphism and thyroid cancer risk under the other three genetic
      models (Pro vs. Arg: OR = 1.20, 95% CI 0.87-1.67, P = 0.262; ProPro vs. ArgArg:
      OR = 1.75, 95% CI 0.88-3.50, P = 0.113; ProPro/ArgPro vs. ArgArg: OR = 1.01, 95%
      CI 0.66-1.55, P = 0.968). Subgroup by ethnicity showed that there was no
      significant association between p53 Arg72Pro polymorphism and thyroid cancer risk
      in both Caucasians and Asians. Thus, p53 Arg72Pro polymorphism may be associated
      with thyroid cancer risk, and ProPro genotype is likely to be a risk factor of
      thyroid cancer.

PMID- 24037913
TI  - Association between vitamin D receptor poly(A) polymorphism and breast cancer
      risk: a meta-analysis.
AB  - Vitamin D receptor (VDR) poly(A) is a common genetic polymorphism in the VDR
      gene, and it has been implicated to be associated with breast cancer risk.
      However, previous studies on the association reported inconclusive results. We
      performed this meta-analysis to comprehensively assess the association. Eligible
      studies were searched in PubMed and EMBASE databases. Odds ratio (OR) and its 95%
      confidence interval (95% CI) were used for statistical analysis. A total 6,631
      cases and 6,718 controls from 11 case-control studies were finally included into
      the meta-analysis. Meta-analysis of total eligible studies showed that VDR
      poly(A) polymorphism was not associated with the risk of breast cancer (S versus
      L: OR = 0.99, 95% CI of 0.90-1.09, P = 0.84; SS versus LL: OR = 0.96, 95% CI of
      0.79-1.18, P = 0.70; SS/LS versus LL: OR = 0.96, 95% CI of 0.83-1.12, P = 0.63;
      SS versus LL/LS: OR = 1.00, 95% CI of 0.91-1.10, P = 0.98). Meta-analysis of
      studies with high quality also showed that there was no association between VDR
      poly(A) polymorphism and breast cancer risk. In addition, in the subgroup
      analysis by ethnicity, no significant association was found among Caucasians.
      Therefore, the meta-analysis suggests that VDR poly(A) polymorphism is not
      associated with the risk of breast cancer. Large well-designed studies are
      necessary to clarify the possible association in Asians.

PMID- 24037914
TI  - Single-nucleotide polymorphisms of GPX1 and MnSOD and susceptibility to bladder
      cancer: a systematic review and meta-analysis.
AB  - Reactive oxygen species-related damage plays a critical role in carcinogenesis.
      Glutathione peroxidase 1 (GPX1) and mitochondrial superoxide dismutase (MnSOD)
      are two key antioxidant enzymes in the defense system against reactive oxygen
      species. This systematic review and meta-analysis was designed to evaluate the
      association of single-nucleotide polymorphisms in GPX1 and MnSOD genes with
      susceptibility to bladder cancer risk. Online databases of PubMed, Embase, China
      National Knowledge Infrastructure, and SinoMed were searched to identify eligible
      studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated
      to estimated the association strength. The fixed effects model and random effects
      model were used to pool the data from different studies. By pooling all eligible
      studies, we found that the GPX1 Pro198Leu polymorphism was associated with a
      significantly increased risk of bladder cancer (Leu vs. Pro, OR = 2.111, 95% CI =
      1.020-4.368, heterogeneity (p < 0.001); LeuPro/LeuLeu vs. ProPro, OR = 1.876, 95%
      CI = 1.011-3.480, heterogeneity (p < 0.001)). No significant association of MnSOD
      Ala-9Val polymorphism with cancer risk was observed (AlaVal/ValVal vs. AlaAla, OR
      = 0.966, 95% CI = 0.754-1.239, heterogeneity (p = 0.390); Vla vs. Ala, OR =
      1.038, 95% CI = 0.782-1.377, heterogeneity (p = 0.015)). This systematic review
      and meta-analysis demonstrated that the GPX1 Pro198Leu polymorphism significantly
      increased susceptibility to bladder cancer, while the MnSOD Ala-9Val polymorphism
      was not associated with bladder cancer risk.

PMID- 24037915
TI  - Matrix metalloproteinase 2 expression and survival of patients with osteosarcoma:
      a meta-analysis.
AB  - A number of studies investigated the impact of matrix metalloproteinase 2 (MMP2)
      expression on the survival of patients with osteosarcoma, but no consistent
      results were reported. To derive a more precise estimate of the prognostic role
      of MMP2 expression in patients with osteosarcoma, we systematically reviewed the
      published studies and carried out a meta-analysis. Cohort studies assessing the
      prognostic role of MMP2 expression in patients with osteosarcoma were included.
      Pooled risk ratio (RR) with 95% confidence intervals (95%CI) was used to assess
      the prognostic role of MMP2 expression. Five cohort studies were eligible in the
      meta-analysis. Overall, high MMP2 expression was associated with increased risk
      of mortality in patients with osteosarcoma during the follow-up (fixed effects RR
      = 2.14, 95%CI 1.66-2.75, P < 0.001). Sensitivity analysis suggested that the
      pooled RR was stable and omitting a single study did not change the significance
      of the pooled RR. There was some possibility of publication bias risk in the meta
      analysis. In conclusion, the meta-analysis suggests that osteosarcoma patients
      with high MMP2 expression have poorer prognosis compared with those with low MMP2
      expression.

PMID- 24037916
TI  - The combination of TRPM8 and TRPA1 expression causes an invasive phenotype in
      lung cancer.
AB  - Our recent studies have shown that hypothermic microenvironment promotes tumor
      progression and that the molecular sensors for cold are the transient receptor
      potential (TRP) channels TRPM8 and TRPA1. To evaluate the contribution of TRPM8
      and TRPA1 to cancer malignancy, we screened cell subpopulations from Lewis lung
      cancer (LLC) using limiting dilutions and Western blotting. We identified that
      LLC-1 cells express 3-fold more TRPM8 than TRPA1, LLC-2 cells express TRPM8 at
      levels similar to TRPA1, and LLC-3 cells express TRPM8 at one-third the level of
      TRPA1. LLC-2 cells showed greater adhesion, migration, invasiveness and
      resistance to hypothermia than LLC-1 and LLC-3 cells, although LLC-2 cells had a
      longer doubling time. TRPM8 or TRPA1 knockdown using siRNA promoted cell
      proliferation and decreased adhesion and invasiveness in LLC-2 cells. When
      assessed for UCP2 staining, LLC-1 cells showed increased staining compared to LLC
      2 cells, both of which had more UCP2-positive cells than the LLC-3 subpopulation.
      In an autophagy assay, hypothermia induced substantially less autophagy in LLC-1
      cells than in LLC-2 cells, which displayed decreased autophagy compared to LLC-3
      cells. Moreover, mice injected with LLC-2 cells had significantly more
      spontaneous and experimental lung metastases and a shorter overall survival time
      than mice injected with LLC-1 or LLC-3 cells. Importantly, LLC-2 cells were also
      more resistant to activated spleen CTL and the chemotherapeutic drug doxorubicin
      than LLC-1 and LLC-3 cells in vitro. Collectively, our data suggest that TRPM8
      induces UCP2 to trigger metabolic transformation, whereas TRPA1 induces autophagy
      during adverse conditions, and the combination of both genes contributes directly
      to an invasive phenotype in lung cancer.

PMID- 24037917
TI  - Functional MUC4 suppress epithelial-mesenchymal transition in lung adenocarcinoma
      metastasis.
AB  - The mucin MUC4 is a high molecular weight membrane-bound transmembrane
      glycoprotein that is frequently detected in invasive and metastatic cancer. The
      overexpression of MUC4 is associated with increased risks for several types of
      cancer. However, the functional role of MUC4 is poorly understood in lung
      adenocarcinoma. Using antisense-MUC4-RNA transfected adenocarcinoma cells, we
      discovered that the loss of MUC4 expression results in epithelial-mesenchymal
      transition (EMT). We found morphological alterations and the repression of the
      epithelial marker E-cadherin in transfected cells. Additionally, the loss of MUC4
      caused the upregulation of the mesenchymal marker vimentin compared to control
      cells. Using a MUC4-knockdown versus control LTEP xenograft mice model (129/sv
      mice), we also found that EMT happened in lung tissues of MUC4-knockdown-LTEP
      xenograft mice. Moreover, antisense-MUC4-RNA transfected cells had a
      significantly increased cellular migration ability in vitro. The loss of MUC4
      also occurred in lung adenocarcinoma patients with lymph node metastases. We
      further investigated MUC4 and found that it plays a critical role in regulating
      EMT by modulating beta-catenin. Taken together, our study reveals a novel role
      for MUC4 in suppressing EMT and suggests that the assessment of MUC4 may function
      as a prognostic biomarker and could be a potential therapeutic target for lung
      adenocarcinoma metastasis.

PMID- 24037918
TI  - The National Lung Screening Trial: results stratified by demographics, smoking
      history, and lung cancer histology.
AB  - BACKGROUND: The National Lung Screening Trial (NLST), which compared lung cancer
      screening with low-dose computed tomography (LDCT) versus chest radiography
      (CXR), demonstrated a statistically significant mortality benefit of LDCT
      screening. In the current study, the authors performed a post hoc analysis to
      examine whether the benefit was affected by various baseline factors, including
      age, sex, and smoking status, and whether it differed by tumor histology.
      METHODS: Lung cancer death rates were computed as events over person-years of
      observation; the mortality risk ratio (RR) was defined as the lung cancer death
      rate in the LDCT versus CXR trial arms. Poisson regression was used to test for
      interactions of sex, age (< 65 years vs >= 65 years), and smoking status (current
      vs former) with trial arm. Mortality RRs were also computed for specific lung
      cancer histologies. RESULTS: The overall mortality RR was 0.92 in men and 0.73 in
      women, with a P value for interaction of .08. RRs were similar for individuals
      aged < 65 years versus those aged >= 65 years (0.82 vs 0.87), and for current
      versus former smokers (0.81 vs 0.91). By tumor histology, mortality RRs were 0.75
      for adenocarcinoma, 0.71 for all non-small cell lung cancers except squamous,
      1.23 for squamous cell carcinoma, and 0.90 for small cell carcinoma. RRs were
      similar for men and women for nonsquamous non-small cell lung cancers (0.71 and
      0.70, respectively); women were found to have lower RRs for small cell and
      squamous cell carcinoma. CONCLUSIONS: A benefit of LDCT did not appear to vary
      substantially by age or smoking status; there was weak evidence of a differential
      benefit by sex. A differential benefit across lung cancer histologies may exist.

PMID- 24037920
TI  - Contrasting echogenicity in flexor digitorum profundus-flexor carpi ulnaris: a
      diagnostic ultrasound pattern in sporadic inclusion body myositis.
AB  - INTRODUCTION: In this study we aimed to clarify whether muscle ultrasound (US) of
      the forearm can be used to differentiate between patients with sporadic inclusion
      body myositis (s-IBM) and those with s-IBM-mimicking diseases. METHODS: We
      compared the echo intensity (EI) of the flexor digitorum profundus (FDP) muscle
      and the flexor carpi ulnaris (FCU) muscles in patients with s-IBM (n = 6),
      polymyositis/dermatomyositis (PM/DM; n = 6), and amyotrophic lateral sclerosis
      (ALS; n = 6). RESULTS: We identified EI abnormalities in 100% of patients with s
      IBM, 33% of those with PM/DM, and 33% of those with ALS. An "FDP-FCU echogenicity
      contrast," a US pattern involving a higher EI in the FDP than in the FCU, was
      observed in all patients with s-IBM, but in none of those with PM/DM or ALS.
      CONCLUSIONS: FDP-FCU echogenicity contrast in muscle US is a sensitive diagnostic
      indicator of s-IBM.

PMID- 24037919
TI  - Single validation of CE method for determining free polysaccharide content in a
      Brazilian meningococcal C conjugate vaccine.
AB  - Neisseria meningitidis group C is an encapsulated bacterium that causes several
      diseases and is associated with high mortality rates, thereby constituting a
      serious public health problem. Bio-Manguinhos/Fiocruz is developing a conjugate
      vaccine by covalent attachment of capsular polysaccharide to hydrazide-activated
      tetanus toxoid through reductive amination. It is necessary to quantify free
      components as a quality control process to prevent exacerbated adverse reactions
      and/or attenuation of vaccine immunogenicity. Thus, this study aimed to develop
      and validate a quality control method appropriate for the separation and
      quantification of free polysaccharide present in this conjugate N. meningitidis
      group C vaccine using CE. CZE was used to remove unbound polysaccharide, and the
      electrophoretic conditions were varied to optimize resolution. We were able to
      develop and validate the proposed method, which was linear and showed a matrix
      effect. Repeatability and partial reproducibility of the method were also
      evaluated. The robustness results showed that control of temperature is required
      for reliable results. The validated method will be used to evaluate the conjugate
      batches submitted for Phase III clinical studies and for routine quality control
      of the conjugate vaccine. 

PMID- 24037921
TI  - Amounts of artificial food colors in commonly consumed beverages and potential
      behavioral implications for consumption in children.
AB  - Artificial food colors (AFCs) are widely used to color foods and beverages. The
      amount of AFCs the Food and Drug Administration has certified over the years has
      increased more than 5-fold since 1950 (12 mg/capita/day) to 2012 (68
      mg/capita/day). In the past 38 years, there have been studies of adverse
      behavioral reactions such as hyperactivity in children to double-blind challenges
      with AFCs. Studies that used 50 mg or more of AFCs as the challenge showed a
      greater negative effect on more children than those which used less. The study
      reported here is the first to quantify the amounts of AFCs in foods (specifically
      in beverages) commonly consumed by children in the United States. Consumption
      data for all foods would be helpful in the design of more challenge studies. The
      data summarized here should help clinicians advise parents about AFCs and
      beverage consumption. 

PMID- 24037922
TI  - Smooth implementation of critical congenital heart defect screening in a newborn
      nursery.
AB  - In January of 2012, University of Arkansas for Medical Sciences began
      implementation of a critical congenital heart disease screening program to
      identify newborns with structural heart defects. The screening used motion
      tolerant pulse oximeters in direct sequence to measure the oxygen levels in the
      right hand and either foot of eligible newborns. Exclusion criteria included
      echocardiogram prior to discharge, age greater than 7 days with continuous
      neonatal intensive care unit monitoring, or death or transfer prior to discharge.
      Of the 1905 infants screened, 3 infants failed screening. Two of the infants had
      atrial septal defects, and 1 had a patent foramen ovale, which was considered a
      false positive. After planning and education, the implementation of critical
      congenital heart disease pulse oximetry screening was successful. With only 1
      false positive in our high-risk population, this should encourage other
      institutions to begin screening eligible infants. 

PMID- 24037924
TI  - Comprehensive treatment of facial skin cancers.

PMID- 24037923
TI  - Calnexin silencing in mouse neonatal cardiomyocytes induces Ca2+ cycling defects,
      ER stress, and apoptosis.
AB  - Calnexin (CNX) is an endoplasmic reticulum (ER) quality control chaperone that
      has been implicated in ER stress. ER stress is a prominent pathological feature
      of various pathologic conditions, including cardiovascular diseases. However, the
      role of CNX and ER stress has not been studied in the heart. In the present
      study, we aimed to characterize the role of CNX in cardiomyocyte physiology with
      respect to ER stress, apoptosis, and cardiomyocyte Ca(2+) cycling. We
      demonstrated significantly decreased CNX mRNA and protein levels by LentiVector
      mediated transduction of targeting shRNAs. CNX silenced cardiomyocytes exhibited
      ER stress as evidenced by increased GRP78 and ATF6 protein levels, increased
      levels of spliced XBP1 mRNA, ASK-1, ERO1a, and CHOP mRNA levels. CNX silencing
      also led to significant activation of caspases-3 and -9. This activation of
      caspases was associated with hallmark morphological features of apoptosis
      including loss of sarcomeric organization and nuclear integrity. Ca(2+) imaging
      in live cells showed that CNX silencing resulted in Ca(2+) transients with
      significantly larger amplitudes but decreased frequency and Ca(2+) uptake rates
      in the basal state. Interestingly, 5 mM caffeine stimulated Ca(2+) transients
      were similar between control and CNX silenced cardiomyocytes. Finally, we
      demonstrated that CNX silencing induced the expression of the L-type voltage
      dependent calcium channel (CAV1.2) but reduced the expression of the sarcoplasmic
      reticulum ATPase (SERCA2a). In conclusion, this is the first study to demonstrate
      CNX has a specific role in cardiomyocyte viability and Ca(2+) cycling through its
      effects on ER stress, apoptosis and Ca(2+) channel expression.

PMID- 24037925
TI  - Facial artery flaps in facial oncoplastic reconstruction.
AB  - The face is one of the common sites for cutaneous cancer localization. It is well
      known that the face is the localization of more than 50% of skin cancers.
      Nowadays, the principles of modern "oncoplasty" recommend the complete excision
      of the cancer and the reconstruction with respect to cosmetic features of the
      face in terms of good color, good softness, and good texture of the flaps,
      utilized in cancer repair. The oncological and cosmetic results of facial
      reconstruction are strictly linked and the modern plastic and reconstructive
      surgeon must respect both oncological and cosmetic aspects. For that reason the
      best solution in facial cancer repair is the utilization of locoregional flaps
      based on the tributary vessels of the facial artery. In consideration of the
      dimension of recipient area to repair, the retroangular flap (RAF) or the
      submental flap could be used. This article is voted to illustrate a very large
      and long-term casuistry dedicated to these flaps. 

PMID- 24037926
TI  - Decision making in nasal reconstruction.
AB  - Nasal reconstruction is a challenging and rewarding discipline. The nasal subunit
      principle dramatically improved the surgeon's ability to reconstruct nasal
      defects by helping disguise incisions within subunit borders and by providing a
      tool to help in reconstructive decision making. Selection of the proper
      reconstruction must include the patient's medicosocial situation and the
      patient's cosmetic concerns. In addition, functional considerations, such as
      nasal obstruction, that may result from the chosen reconstruction must be
      carefully considered. For any defect, the most appropriate reconstructive
      technique is the simplest and most cost-effective method that meets each
      individual patient's medical, functional, social, and cosmetic goals. 

PMID- 24037927
TI  - Role of secondary intention healing.
AB  - Secondary intention wound healing is a simple, yet powerful tool in facial
      reconstruction. Considered as the most elementary form of wound reconstruction,
      it is often unused because of concern about the predictability of the result and
      the desire for immediate reconstruction. Secondary intention wound healing can
      successfully be used for reconstruction of defects for patients who may not be
      candidates for involved surgical procedures and should be considered an ideal
      form of reconstruction for certain defects. In general, superficial defects
      located in concave areas lead to the best results. Proper wound care, including
      keeping the wound clean and moist, is a simple, but important, aspect of result
      optimization. Avoiding the use of secondary intention healing on facial anatomic
      sites known to produce poor results minimizes complications. Complications
      encountered may include ectropion, nasal obstruction, alar retraction, alopecia,
      and poor cosmesis. 

PMID- 24037928
TI  - Post-skin cancer alar reconstruction.
AB  - The ala is a cosmetically and functionally important portion of the nose and its
      reconstruction represents a surgical challenge. This article reviews the
      reconstructive options for alar wounds. 

PMID- 24037929
TI  - Surgical management of melanoma.
AB  - Historically, the surgical management for melanoma was ossified for nearly 50
      years with the standard of care being wide local excisions with 5-cm margins.
      Several clinical studies have now brought to light new data that have enabled
      academic groups such as the American Joint Committee on Cancer and the National
      Comprehensive Cancer Network to update surgical guidelines reliant on evidence
      with long-term follow-up. In addition, basic research at the bench has dispelled
      the myth that all melanomas are genetically identical and behave in a homogeneous
      way on the basis of the Breslow depth of the original tumor. It is now known that
      although all melanomas arise from the melanocyte, melanoma encompasses a variety
      of cancers that are genetically distinct with variable predicted outcomes often
      associated with the anatomic location of the tumor. This article cites the
      evidence on which the current surgical guidelines are based and it addresses some
      of the ongoing controversies regarding the surgical management of the various
      types of melanoma. 

PMID- 24037930
TI  - Chemoprevention of nonmelanoma skin cancer.
AB  - Chemoprevention is suitable for patients who are at high risk of development of
      numerous or invasive nonmelanoma skin cancers (NMSCs). Various substances have
      been studied as potential chemopreventive agents for NMSC. Oral retinoids have
      been proven to be effective in the suppression of new squamous cell carcinoma
      (SCC) development. Patients need to stay on oral retinoids as long as
      chemoprevention is needed with careful monitoring of the dose and side effects.
      Topical retinoids are not effective in prevention of NMSC. In organ transplant
      patients with aggressive or numerous skin cancers, decrease in the
      immunosuppression or switch to mammalian target of rapamycin inhibitors
      (sirolimus or everolimus) can be considered. Field therapy for areas of severe
      actinic damage with photodynamic therapy, imiquimod, 5-fluorouracil, ingenol
      mebutate, or diclofenac sodium may theoretically decrease the risk of SCC through
      treatment of precancerous changes. However, there is limited data regarding
      efficacy of these agents in chemoprevention of NMSC. Epidemiologic studies
      suggest a protective role for nonsteroidal anti-inflammatory agents in
      development of NMSC. Limited data support chemopreventive effect of
      difluoromethylornithine and T4 endonuclease V for actinic keratoses and basal
      cell carcinoma. Amongst dietary factors, low-fat diet, limonene from citrus fruit
      peel, and caffeine may protect against NMSC. 

PMID- 24037931
TI  - Skin cancers of the external auditory canal.
AB  - Skin cancers of the external auditory canal are rare tumors treated by a variety
      of medical and surgical specialties. Treatment of skin cancer is generally
      successful; however, tumors involving this anatomic location can be aggressive
      and require a multidisciplinary approach to treatment. This multidisciplinary
      review provides facial plastic surgeons, caring for these patients, an updated
      approach to cancers of the external auditory canal focusing on findings that may
      indicate more aggressive disease and warrant expanded workup and treatment. 

PMID- 24037932
TI  - Rare skin malignancies of the head and neck: a review.
AB  - The skin of the head and neck is a common location for skin cancers to develop.
      The majority of skin cancers of the head and neck are basal cell and squamous
      cell carcinomas, with melanoma also occurring at a significant incidence.
      However, there are many other histologies that occur and raise diagnostic and
      treatment challenges. In this article, we review some of the more common
      histologies that are classified as rare skin malignancies of the head and neck.
      Specifically, epidemiology, pathogenesis, histopathology, and treatment options
      for each of these histologies will be discussed. There is a growing emphasis on
      Mohs micrographic surgery in the treatment of these lesions, although, some are
      not amenable to this technique. A multidisciplinary approach is frequently useful
      in their treatment. 

PMID- 24037933
TI  - Reconstructing complex central facial defects involving multiple cosmetic
      subunits.
AB  - Defects of the central face can pose significant reconstructive challenges and
      are some of the most frequently encountered defects in facial reconstructive
      surgery. Familiarity with the repair of such defects is essential. At our
      institution, we have found that a systematic approach to central facial defects
      allows for superior results. We present that approach here using several cases to
      demonstrate the intraoperative planning involved. The cosmetic units and subunits
      within the defect must be identified. The defect must then be assessed for
      structural defects and deep soft tissue defects, which can be repaired utilizing
      cartilage grafts and hinge flaps respectively. Superficial defects of the cheek,
      lip, and nasal sidewall can then be assessed and repaired, taking advantage of
      the available tissue reservoirs using adjacent sliding flaps. The remaining
      distal nasal defect can then be repaired, depending on size, with a full
      thickness skin graft, a cheek interpolation flap, or if necessary, a paramedian
      forehead flap. This systematic approach to reconstructing central facial defects
      simplifies seemingly complex reconstructive challenges and optimizes results. 

PMID- 24037934
TI  - Skin cancer in immunosuppressed patients.
AB  - Organ transplant recipients suffer from an increased incidence and recurrence
      rate of nonmelanoma skin cancers. These cancers are often more aggressive than
      those in the general population, resulting in significant morbidity and
      mortality. Often times, routine treatment modalities are not adequate and the use
      of different management strategies is necessary. Treatment modalities, including
      surgical excision, Mohs micrographic surgery, physically destructive modalities,
      topical therapy, and photodynamic therapy may be used. Combinations of these
      therapies may be used in rotation for treatment of extensive field disease.
      Chemoprophylaxis with oral retinoids and alteration of the immune suppression
      regimen may be indicated for specific cases. In addition, newly emerging
      therapies for squamous cell carcinomas including cetuximab and capecitabine may
      offer heightened control in organ transplant patients with significant cutaneous
      disease. 

PMID- 24037935
TI  - Prelamination to reconstruct internal nasal lining.
AB  - The reconstruction of internal lining in nasal reconstruction is critical to the
      final result. Most established techniques carry important drawbacks, which
      include limited available lining surface area, compromise of nasal physiologic
      function, or donor site morbidity. In this report, we demonstrate a technique
      that is reliable, technically facile, and allows for the reconstruction of large
      surface areas: the creation of a bilaminated forehead flap by in situ split
      thickness skin grafting. The use of the bilaminated forehead flap in subsequent
      reconstructive steps allows for dependable reconstruction. All relevant technical
      steps are illustrated in detail. 

PMID- 24037936
TI  - Surgical treatment of large skin cancers.
AB  - Treatment of large facial skin cancers with surgery is a multistep process.
      First, both the patient and the lesion must be evaluated to ensure that surgery
      is the most appropriate form of treatment. When surgery is deemed appropriate,
      the method of tumor removal must be chosen and may vary depending on the size and
      type of lesion. In many cases, Mohs surgery is appropriate, but in other cases,
      excision with en face permanent section margins will be elected. Reconstruction
      should only be undertaken when negative margins have been assured. Repair may
      entail coverage or aesthetic coverage, depending on patient factors and
      preferences. Flaps will generally increase cosmesis but are often not feasible
      once a wound reaches a certain size. 

PMID- 24037937
TI  - Reconstructing the extended nasal tip defect.
AB  - Reconstruction of large facial defects requires surgical skill, an understanding
      of engineering principles, an artistic eye, and patience to design the most
      elegant solution for each patient. Extended nasal tip defects, which may involve
      additional facial subunits, require even more thoughtful analysis and planning.
      Reconstructive surgeons need to be aware of the pros and cons of various options
      for flaps, the use of a delay stage, and sequencing and scheduling of staged
      operations to achieve an optimal outcome. 

PMID- 24037938
TI  - Superficial musculoaponeurotic system flap for reconstruction of the intraoral
      defects.
AB  - Intraoral tumors are the main causes of the intraoral and maxillofacial defects.
      Skin grafts and several soft tissue flaps can be used to reconstruct the
      intraoral defects including local, regional, and free flaps. Here we present a
      case of intraoral adenocystic carcinoma treated with segmental maxillectomy,
      resection of the parotid gland, and the buccal mucosa leaving a full-thickness
      intraoral defect. The defect was covered with a superficial musculoaponeurotic
      system (SMAS) flap elevated using the preauricular incision. Reconstruction with
      SMAS flap for temporal defects and parotidectomy defects has been described in
      the literature. To our knowledge, the use of this flap for intraoral defects has
      not been reported. The proximity of the flap to the defect and ease of harvest in
      cases including total parotidectomy are few of the reasons we use and recommend
      this flap in reconstruction of intraoral defects. 

PMID- 24037940
TI  - William Foote Whyte, Street Corner Society and social organization.
AB  - Social scientists have mostly taken it for granted that William Foote Whyte's
      sociological classic Street Corner Society (SCS, 1943) belongs to the Chicago
      school of sociology's research tradition or that it is a relatively independent
      study which cannot be placed in any specific research tradition. Social science
      research has usually overlooked the fact that William Foote Whyte was educated in
      social anthropology at Harvard University, and was mainly influenced by Conrad M.
      Arensberg and W. Lloyd Warner. What I want to show, based on archival research,
      is that SCS cannot easily be said either to belong to the Chicago school's urban
      sociology or to be an independent study in departmental and idea-historical
      terms. Instead, the work should be seen as part of A. R. Radcliffe-Brown's and W.
      Lloyd Warner's comparative research projects in social anthropology.

PMID- 24037939
TI  - Increased nanoparticle-loaded exogenous macrophage migration into the brain
      following PDT-induced blood-brain barrier disruption.
AB  - BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT)-induced disruption of the
      blood-brain barrier (BBB) has been investigated as a technique for the delivery
      of therapeutic agents to selective regions of the brain. The purpose of this
      study was to determine the effects of PDT on the migration of systemically
      administered exogenous macrophages (Ma) loaded with iron oxide nanoparticles in
      non-tumor bearing rats. MATERIALS AND METHODS: A control group consisting of
      three Sprague-Dawley rats was injected with iron oxide-loaded rat alveolar Ma via
      jugular vein catheter while two animals were subjected to intracranial injection
      of iron oxide-loaded Ma. PDT-treated animals were injected with photosensitizer
      (AlPcS2a ; 1 mg/kg i.p.) followed by light irradiation (wavelength = 670 nm;
      light dose = 2.5 J) 48 hours later. Light irradiation was performed through the
      skull. Prior to light irradiation, iron oxide-loaded Ma were administered to each
      animal. Animals in all groups were imaged in a 7 Tesla (T) magnetic resonance
      (MR) imager to determine the extent of PDT-induced edema and to evaluate for the
      presence of iron oxide nanoparticles. Animals were sacrificed 7 days post-Ma
      administration and their brains analyzed for the presence of iron oxide using
      Perls staining. RESULTS: Significant uptake of iron oxide nanoparticles by rat
      alveolar Ma was observed thus providing the rationale for their use as delivery
      vectors. Histopathological analyses failed to find evidence of iron oxide in
      normal rat brain. Accumulations of iron oxide-loaded Ma were observed in both MR
      images and histological sections of non-tumor bearing rat brain following PDT
      induced disruption of the BBB. CONCLUSIONS: MR imaging was shown to be useful for
      localizing iron-oxide loaded Ma in rat brains. Exogenous Ma are incapable of
      traversing the normal BBB and therefore, the use of Ma as delivery vehicles into
      the brain requires selective disruption of the BBB.

PMID- 24037941
TI  - Differences in coronary blood flow in aortic regurgitation and systemic arterial
      hypertension have implications for diastolic blood pressure targets: a systematic
      review and meta-analysis.
AB  - The objective was to evaluate coronary blood flow (CBF) in patients with systemic
      arterial hypertension (HTN) and to compare it with CBF in patients with aortic
      regurgitation (AR). A systematic literature search was conducted using the
      reference terms "coronary blood flow" and either "aortic regurgitation" or
      "hypertension." The selection criteria included CBF measurement in a concomitant
      control group, except studies evaluating CBF with aortic-valve replacement
      surgery. Twenty-two studies met the inclusion criteria. There were 318 persons
      with HTN, with 185 controls; and 102 persons with AR, with 144 controls. Despite
      an overall increase in CBF in HTN, CBF per gram of left ventricular mass was
      significantly (P < 0.0001) reduced. In contrast, CBF per gram of left ventricular
      mass was significantly (P = 0.004) increased in AR. Aortic regurgitation was
      associated with a significant (P < 0.0001) increase in CBF during systole and
      away from diastole, in contrast to persons with HTN. Aortic-valve replacement
      reversed the increase in systolic CBF. These data suggest that patients with HTN
      are more vulnerable than patients with AR to lower diastolic blood pressure
      (DBP), because resting CBF is compromised in HTN. Furthermore, patients with HTN
      may not compensate for DBP reductions by shifting CBF to systole, such as can
      occur with the low DBP in AR. Lower DBP in patients with AR cannot be used to
      justify treating patients with HTN to similar DBP because of the dramatic
      differences in CBF between the 2 conditions. 

PMID- 24037942
TI  - Short report: Limited effectiveness of screening mammography in addition to
      clinical breast examination by trained nurse midwives in rural Jakarta,
      Indonesia.
AB  - Low- and middle-income countries (LMICs) are undergoing an increase in incidence
      of breast cancer, but have inadequate resources to implement mammographic
      screening. Clinical breast examination (CBE) has been suggested as an alternative
      to mammography in these settings. We compared the results of CBE screening by 47
      midwives and 15 trained lay health workers to results of independently performed
      mammographic screening in an unscreened population of 1,179 women in Jakarta,
      Indonesia. Two hundred and eight-nine (24.5%) of the screened women had a
      suspicious finding on CBE and/or mammography. Sixty-nine (23.9%) of these women
      had both an abnormal CBE and mammogram; 98 (33.9%) had an abnormal CBE, but a
      normal mammogram; and 122 (42.2%) had a normal CBE and an abnormal mammogram.
      Fourteen breast cancers were diagnosed. Of these, 13 were identified by both
      mammogram and CBE. One breast cancer was identified from an abnormal mammogram,
      but had a normal CBE. One hundred and sixty-seven (14.2%) of the CBEs required
      additional work-up to diagnose 13 of the 14 cancers detected by mammography. In
      comparison, 191 (16.2%) of mammograms required additional work-up to diagnose the
      14 cancers. Unfortunately, only 42.8% of the women diagnosed with cancer returned
      for treatment. In an unscreened population in LMICs such as Indonesia, CBE is
      nearly as effective as mammography in detecting prevalent breast cancers. However
      identifying and overcoming barriers to appropriate treatment of women who are
      identified as having breast cancer are essential to the success of any screening
      program. 

PMID- 24037943
TI  - Polymorphisms in the HIV-1 gp41 env gene, natural resistance to enfuvirtide (T
      20) and pol resistance among pregnant Brazilian women.
AB  - The selective pressure of antiretroviral drugs (ARVs) targeting HIV-1 pol can
      promote drug resistance mutations in other genomic regions, such as env. Drug
      resistance among women should be monitored to avoid horizontal and mother-to
      child transmission. To describe natural resistance to T-20 (enfuvirtide), gp41
      env polymorphisms, mutations in pol and HIV-1 subtypes, 124 pregnant women were
      recruited. For 98 patients, the gp41 env, protease (PR) and reverse transcriptase
      (RT) fragments were sequenced. The patients were ARV naive (n = 30), taking
      mother-to-child transmission prophylaxis (n = 50), or being treated with highly
      active ARV therapy/HAART (n = 18). The Stanford and IAS/USA databases and other
      sources were used to analyze PR/RT, gp41 env resistance mutations. The HIV-1
      genetic diversity was analyzed by REGA/phylogenetic analyses. The patients'
      median age was 25 years (range, 16-42), 18.4% had AIDS. The frequency of natural
      resistance to T-20 (N42D, L44M, and R46M-low-impact mutations) was 6.1% (6/98);
      20.4% (20/98) had compensatory mutations in HR2. The prevalence of transmitted
      drug resistance in the pol was 13.3% (4/30), and the prevalence of secondary drug
      resistance was 33.3% (6/18). Two patients were infected with multidrug
      resistant/MDR viruses. The analysis of HIV-1 subtypes (PR/RT/gp41) revealed that
      61.2% (60/98) were subtype B, 12.2% (12/98) were subtype C, 4.1% (4/98) were
      subtype F1, and 22.4% (22/98) were possible recombinants (BF1 = 20.4%; BC = 2%).
      Natural resistance to T-20 was not associated with pol resistance or previous ARV
      use. The high rate of secondary resistance, including MDR, indicates that the
      number of women that may need T-20 salvage therapy may be higher than
      anticipated.

PMID- 24037944
TI  - Evaluation of cinnamon essential oil microemulsion and its vapor phase for
      controlling postharvest gray mold of pears (Pyrus pyrifolia).
AB  - BACKGROUND: Essential oil of cinnamon (CM) is a potential alternative to chemical
      fungicides. Thus this work aimed to investigate the possible effects of CM
      microemulsions on decay developments and qualitative properties of pears.
      RESULTS: The decay incidence of samples treated with 500 ug L-1 microemulsion was
      significantly reduced by 18.7% in comparison to that of 500 ug L-1 non
      microemulsion after 4 days' storage at 20  degrees C. In the vapor phase, the CM
      microemulsion with the lowest concentration had the best control for decay
      incidence and lesion diameter. The interval between inoculations also influenced
      decay development. Pears treated with Botrytis cinerea and immediately followed
      by CM microemulsion showed the lowest decay incidence. Moreover, in the natural
      decay experiment, the percentage of rotted pears was 3.8% in the CM microemulsion
      treatment and 5.8% in the control. CM microemulsion delayed the loss of ascorbic
      acid, yet it had no significant influence on pear qualities such as firmness and
      color. CONCLUSION: CM microemulsion may be an alternative way to control the gray
      mold of pears without a negative influence on its qualities.

PMID- 24037945
TI  - Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: is
      the glass half full or half empty?

PMID- 24037946
TI  - Wnt16 is involved in intramembranous ossification and suppresses osteoblast
      differentiation through the Wnt/beta-catenin pathway.
AB  - In the course of embryonic development skeletal elements form either through
      intramembranous or endochondral ossification. Wnt proteins play diverse roles
      during vertebrate skeletal development. Wnt16 is a key factor in developing long
      bones, but its exact role in craniofacial bone formation remains unclear. This
      study was initially undertaken to investigate the expression of Wnt16 during
      craniofacial bone development in mouse embryos. Wnt16 expression in the osteoid
      of calvaria, maxilla, and mandible started later than that of ALP and osteocalcin
      (OCN), but before mineralization of the craniofacial bones, suggesting that Wnt16
      is involved in intramembranous ossification in the head. To confirm this, MC3T3
      E1 cells were transfected with an adenovirus containing Wnt16 (Ad-Wnt16). Ad
      Wnt16 cells showed decreased ALP activity and less mineralized nodule formations
      compared with control cells. In addition, the mRNA levels of osteogenic markers
      were reduced. Moreover, Wnt16 activated beta-catenin signaling in MC3T3-E1 cells
      at both transcription and protein levels as shown by a TOPflash luciferase
      reporter gene assay and western blot analysis. On the other hand, Wnt/beta
      catenin pathway blockade by Dickkopf 1 abrogated the suppression of
      mineralization by Wnt16. Our findings suggest that Wnt16 is involved in
      intramembranous ossification and suppresses osteoblast differentiation through
      the Wnt/beta-catenin pathway.

PMID- 24037947
TI  - Sequence context and crosslinking mechanism affect the efficiency of in vivo
      capture of a protein-protein interaction.
AB  - Protein-protein interactions (PPIs) are essential for implementing cellular
      processes and thus methods for the discovery and study of PPIs are highly
      desirable. An emerging method for capturing PPIs in their native cellular
      environment is in vivo covalent chemical capture, a method that uses nonsense
      suppression to site specifically incorporate photoactivable unnatural amino acids
      (UAAs) in living cells. However, in one study we found that this method did not
      capture a PPI for which there was abundant functional evidence, a complex formed
      between the transcriptional activator Gal4 and its repressor protein Gal80. Here
      we describe the factors that influence the success of covalent chemical capture
      and show that the innate reactivity of the two UAAs utilized, (p
      benzoylphenylalanine (pBpa) and p-azidophenylalanine (pAzpa)), plays a profound
      role in the capture of Gal80 by Gal4. Based upon these data, guidelines are
      outlined for the successful use of in vivo photo-crosslinking to capture novel
      PPIs and to characterize the interfaces.

PMID- 24037950
TI  - Positive interactions between irrawaddy dolphins and artisanal fishers in the
      Chilika Lagoon of eastern India are driven by ecology, socioeconomics, and
      culture.
AB  - In human-dominated landscapes, interactions and perceptions towards wildlife are
      influenced by multidimensional drivers. Understanding these drivers could prove
      useful for wildlife conservation. We surveyed the attitudes and perceptions of
      fishers towards threatened Irrawaddy dolphins (Orcaella brevirostris) at Chilika
      Lagoon India. To validate the drivers of fisher perceptions, we : (1) observed
      dolphin foraging behavior at stake nets, and (2) compared catch per unit effort
      (CPUE) and catch income of fishers from stake nets in the presence and absence of
      foraging dolphins. We found that fishers were mostly positive towards dolphins,
      believing that dolphins augmented their fish catch and using culture to express
      their perceptions. Foraging dolphins were observed spending half their time at
      stake nets and were associated with significantly higher catch income and CPUE of
      mullet (Liza sp.), a locally preferred food fish species. Wildlife conservation
      efforts should use the multidimensional drivers of human-wildlife interactions to
      involve local stakeholders in management. 

PMID- 24037951
TI  - Targeting therapy to the neuromuscular junction: proof of concept.
AB  - INTRODUCTION: The site of pathology in myasthenia gravis (MG) is the
      neuromuscular junction (NMJ). Our goal was to determine the ability to direct
      complement inhibition to the NMJ. METHODS: A single-chain antibody directed
      against the alpha subunit of the acetylcholine receptor was synthesized (scFv-35)
      and coupled to decay-accelerating factor (DAF, scFv-35-DAF). scFv-35-DAF was
      tested in a passive model of experimentally acquired MG. RESULTS: Administration
      of scFv-35-DAF to mice deficient in intrinsic complement inhibitors produced no
      weakness despite confirmation of its localization to the NMJ and no evidence of
      tissue destruction related to complement activation. Rats with experimentally
      acquired MG treated with scFV-35-DAF showed less weakness and a reduction of
      complement deposition. CONCLUSIONS: We demonstrate a method to effectively target
      a therapeutic agent to the NMJ.

PMID- 24037952
TI  - Determination of lipophilicity of gamma-butyrolactone derivatives with
      anticonvulsant and analgesic activity using micellar electrokinetic
      chromatography.
AB  - The lipophilicity of a library of 30 derivatives of dihydrofuran-2(3H)-one (gamma
      butyrolactone) was determined by MEKC. Calibration curve prepared for ten
      reference drugs enabled to calculate partition coefficient (log P) for novel
      compounds. The results of MEKC analysis were compared with lipophilicity
      coefficients determined by RP-TLC (R(M0)) and computational (Mlog P, Clog P)
      methods. Good correlation was observed between the results obtained by both
      experimental methods: the MEKC parameters log k and relative lipophilicity R(MO).
      The relationship between determined log P values and results of the computational
      prediction was weaker. Analysis of the relationship between lipophilicity and
      anticonvulsant activity showed statistically significant differences between mean
      values of log P coefficients for group of active (2.18) and inactive (1.51)
      compounds in the maximal electroshock test.

PMID- 24037953
TI  - Cancer drug prices and the free-market forces.

PMID- 24037954
TI  - Methamphetamine-associated cardiomyopathy.
AB  - Methamphetamine and related compounds are now the second most commonly used
      illicit substance worldwide, after cannabis. Reports of methamphetamine
      associated cardiomyopathy (MAC) are increasing, but MAC has not been well
      reviewed. This analysis of MAC will provide an overview of the pharmacology of
      methamphetamine, historical perspective and epidemiology, a review of case and
      clinical studies, and a summary of the proposed mechanisms for MAC. Clinically,
      many questions remain, including the appropriate therapeutic interventions for
      MAC, the incidence and prevalence of cardiac pathology in methamphetamine users,
      risk factors for developing MAC, and prognosis of these patients. In conclusion,
      recognition of the significance of MAC among physicians and other medical
      caregivers is important given the growing use of methamphetamine and related
      stimulants worldwide. 

PMID- 24037956
TI  - Simple and validated UHPLC method coupled to UV detection for determination of
      daptomycin in human plasma and urine.
AB  - Daptomycin, a lipopeptide antibiotic with excellent activity against Gram
      positive bacteria, is excreted primarily by the kidneys. Development of effective
      chromatographic methodologies for the determination of daptomycin in human
      specimens is necessary for clinical use. This study developed a simple and
      validated ultra-high-performance liquid chromatography method coupled to
      ultraviolet detection for determination of daptomycin in human plasma and urine.
      After the pretreatments involving protein precipitation, the supernatants were
      separated using a 2.3 um particle size octadecylsilyl column, and the run time
      was 1 min. The calibration curves were linear over the concentration ranges of 2
      200 mg/L for plasma and 25-300 mg/L for urine. Intra- and inter-assay precision
      and accuracy values of plasma were within 13.5 and 92-100% and within 10.7 and
      100-107%, respectively. Those of urine were within 5.0 and 101-104% and within
      3.7 and 100-101%, respectively. The validated method was applied to the
      determination of plasma and urine samples in patients receiving 4-6 mg/kg of
      intravenous daptomycin, resulting in sufficient sensitivity for evaluating the
      plasma exposure and urinary excretion. In conclusion, the present method with
      acceptable analytical performance can be helpful for evaluating the
      pharmacokinetic disposition of daptomycin in clinical settings.

PMID- 24037955
TI  - The presence of prostate cancer at biopsy is predicted by a number of genetic
      variants.
AB  - Several single nucleotide polymorphisms (SNPs) have been associated with an
      elevated risk of prostate cancer risk. It is not established if they are useful
      in predicting the presence of prostate cancer at biopsy or if they can be used to
      define a low-risk group of men. In this study, 4,548 men underwent a prostate
      biopsy because of an elevated prostate specific antigen (PSA; >=4 ng/mL) or an
      abnormal digital rectal examination (DRE). All men were genotyped for 11 selected
      SNPs. The effect of each SNP, alone and in combination, on prostate cancer
      prevalence was studied. Of 4,548 men: 1,834 (40.3%) were found to have cancer. A
      positive association with prostate cancer was seen for 5 of 11 SNPs studied
      (rs1800629, rs1859962, rs1447295, rs4430796, rs11228565). The cancer detection
      rate rose with the number of SNP risk alleles from 29% for men with no variant to
      63% for men who carried seven or more risk alleles (OR = 4.2; p = 0.002). The SNP
      data did not improve the predictive power of clinical factors (age, PSA and DRE)
      for detecting prostate cancer (AUC: 0.726 vs. 0.735; p = 0.4). We were unable to
      define a group of men with a sufficiently low prevalence of prostate cancer that
      a biopsy might have been avoided. In conclusion, our data do not support the
      routine use of SNP polymorphisms as an adjunct test to be used on the context of
      prostate biopsy for Polish men with an abnormal screening test.

PMID- 24037957
TI  - MR and CT based treatment planning for mTHPC mediated interstitial photodynamic
      therapy of head and neck cancer: description of the method.
AB  - BACKGROUND AND OBJECTIVE: Interstitial photodynamic therapy is a potentially
      important tool in the management of voluminous or deep-seated recurrent head and
      neck cancers. STUDY DESIGN/METHODS: The described treatment algorithm in this
      manuscript consists of the treatment simulation, implantation of light sources,
      verification, modification of the treatment plan if necessary, and illumination.
      The tumor is delineated on imaging sections (CT, MRI, and/or PET/CT) and the
      treatment is simulated by virtually introducing light sources to the tumor volume
      on specially modified brachytherapy software. This enables us to determine if the
      treatment is technically feasible, and information about approximate number and
      location of light sources necessary. Following implantation of catheters in which
      the light sources will be introduced, CT or MR scan is performed to verify the
      actual location of the implanted catheters. The verification-CT is imported to
      the software and co-registered with pre-treatment images to observe the
      deviations from the simulation. The simulation is run again with the actual
      position of the light sources to determine if any additional light sources are
      necessary and adaptation of the source length in order to cover the tumor volume
      (modification). Thereafter the tumor is illuminated. RESULTS: This method has the
      potential to help with identifying iPDT feasible patients by simulating before
      the actual treatment. The suboptimal placement of light sources can be identified
      and corrected. The simulations were documented and saved for subsequent
      evaluation of the technique. CONCLUSION: The proposed technique can help
      standardize and document iPDT.

PMID- 24037958
TI  - CCR5 deficiency and severe polio infection in the 1984 outbreak in Finland.
AB  - CCR5, a leukocyte chemoattractant receptor for chemokines CCL3, CCL4, and CCL5,
      promotes innate and adaptive immune responses by mediating leukocyte trafficking
      within lymph nodes and to peripheral tissues and is also known as a co-receptor
      for HIV cell entry. Homozygous inheritance of a complete loss-of-function
      mutation in CCR5 (CCR5Delta32/CCR5Delta32) is associated with symptomatic
      neuroinflammatory disease in humans with West Nile and Tickborne Encephalitis
      flavivirus infections. This study sought to establish whether CCR5 deficiency
      could also be a determinant of clinical outcome after infection by poliovirus
      which results in central nervous system damage in only a small proportion of
      cases. We analyzed serum samples from seven patients and 79 controls, collected
      during the 1984-1985 polio outbreak in Finland, where CCR5Delta32 is relatively
      common in the general population. The results excluded CCR5 deficiency as the
      sole determinant of severe neurologic disease after poliovirus infection in this
      population.

PMID- 24037959
TI  - Structural characterization of the regulatory domain of brain carnitine
      palmitoyltransferase 1.
AB  - Neurons contain a mammalian-specific isoform of the enzyme carnitine
      palmitoyltransferase 1 (CPT1C) that couples malonyl-CoA to ceramide levels
      thereby contributing to systemic energy homeostasis and feeding behavior. In
      contrast to CPT1A, which controls the rate-limiting step of long-chain fatty acid
      beta-oxidation in all tissues, the biochemical context and regulatory mechanism
      of CPT1C are unknown. CPT1 enzymes are comprised of an N-terminal regulatory
      domain and a C-terminal catalytic domain (CD) that are separated by two
      transmembrane helices. In CPT1A, the regulatory domain, termed N, adopts an
      inhibitory and non-inhibitory state, Nalpha and Nbeta, respectively, which differ
      in their association with the CD. To provide insight into the regulatory
      mechanism of CPT1C, we have determined the structure of its regulatory domain
      (residues Met1-Phe50) by NMR spectroscopy. In relation to CPT1A, the inhibitory
      Nalpha state was found to be structurally homologues whereas the non-inhibitory
      Nbeta state was severely destabilized, suggesting a change in overall regulation.
      The destabilization of Nbeta may contribute to the low catalytic activity of
      CPT1C relative to CPT1A and makes its association with the CD unlikely. In
      analogy to the stabilization of Nbeta by the CPT1A CD, non-inhibitory
      interactions of N of CPT1C with another protein may exist.

PMID- 24037960
TI  - Effects of carbon monoxide on quality, nutrients and antioxidant activity of post
      harvest jujube.
AB  - BACKGROUND: To effectively extend the shelf life of fresh jujube, carbon monoxide
      (CO), as a small molecular gas, was applied to fumigate fresh jujube. The quality
      and antioxidant activity of jujubes fumigated with carbon monoxide at
      concentrations of 0 (control), 5, 10, 20 and 40 umol L-1 for 1 h under ambient
      temperature were investigated. RESULTS: The jujube fumigated with 10 umol L-1 CO
      showed the best preserving effect amongst all samples. At 30 days, the decay
      incidence of jujube fumigated with 10 umol L-1 CO is only two-thirds of that of
      control sample; its red index and weight loss rate were 22.8% and 19.4% lower,
      and its firmness, soluble solids content (SSC) and acidity were 18.7%, 5.4% and
      12.2% higher than that of control samples, respectively. Its vitamin C and total
      flavonoid contents were also the highest. However, no significant difference in
      total polyphenol content was found. The jujubes treated with 10 umol L-1 CO
      exhibited the highest antioxidant activity in terms of reducing power and 2,2
      diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl radical scavenging activity. However,
      the jujubes fumigated with 40 umol L-1 CO showed inferior characteristics
      compared with the control sample. CONCLUSION: Fumigating jujubes with proper
      concentration of CO probably is a potential novel method for post-harvest jujube
      preservation in the future.

PMID- 24037961
TI  - Utility of death certificate data in predicting cancer incidence.
AB  - BACKGROUND: Studies often rely on death certificates to identify cancer
      occurrence. This research assessed the death certificate's ability to reflect
      cancer incidence and factors that influence agreement with cancer registry data.
      METHODS: This study compared death certificates to cancer incidence data for an
      occupational cohort of 1,795 deceased workers who were registered by the Iowa
      Cancer Registry (ICR) between 1973 and 2005. Logistic regression models examined
      the effects of factors such as survival time, age at diagnosis, and gender on the
      odds of agreement between death certificate and incidence data. RESULTS: Death
      certificates under-reported cancer incidence by 10-100%, depending on site. A 1
      year increase in survival decreased the odds of agreement between death
      certificate and ICR data by 18%. Younger and female workers had increased odds of
      agreement. CONCLUSIONS: Death certificates can be useful predictors of cancer
      incidence, particularly for diseases with shorter survival and among subjects
      diagnosed earlier in life.

PMID- 24037962
TI  - Angiotensin II activation of TRPC6 channels in rat podocytes requires generation
      of reactive oxygen species.
AB  - Angiotensin II (AII) plays a major role in the progression of chronic kidney
      diseases. Podocytes are essential components of the ultrafiltration apparatus,
      and are targets for AII signaling. AII has been shown to increase generation of
      reactive oxygen species (ROS) in podocytes. Canonical transient receptor
      potential-6 (TRPC6) channels stimulate Ca(2+) influx in podocytes, and have been
      implicated in glomerular disease. We observed that AII increased cationic
      currents in rat podocytes in an isolated glomerulus preparation in which
      podocytes are still attached to the underlying capillary. This effect was
      completely blocked by SKF-96365, by micromolar La(3+) , and by siRNA knockdown of
      TRPC6, indicating that TRPC6 is the primary source of Ca(2+) influx mobilized by
      endogenously expressed angiotensin II receptors in these cells. These responses
      were also blocked by the AT1R antagonist losartan, the phospholipase C inhibitor
      D-609, and by inhibition of G protein signaling. The pan-protein kinase C
      inhibitor chelerythrine had no effect. Importantly, pretreating podocytes with
      the ROS quencher manganese (III) tetrakis (4-benzoic acid) porphyrin chloride
      (MnTBAP) eliminated AII activation of TRPC6. Significant reductions of AII
      effects on podocyte TRPC6 were also observed after pretreatment with NADPH
      oxidase inhibitors apocynin or diphenylene iodonium (DPI). These data suggest
      that ROS production permits activation of TRPC6 channels by G protein and PLC
      dependent cascades initiated by AII acting on AT1Rs in podocytes. This pathway
      also provides a basis whereby two forms of cellular stress-oxidative stress and
      Ca(2+) overload-converge on common pathways relevant to disease.

PMID- 24037963
TI  - Hepatic histological findings in suspected drug-induced liver injury: systematic
      evaluation and clinical associations.
AB  - Drug-induced liver injury (DILI) is considered to be a diagnosis of exclusion.
      Liver biopsy may contribute to diagnostic accuracy, but the histological features
      of DILI and their relationship to biochemical parameters and outcomes are not
      well defined. We have classified the pathological pattern of liver injury and
      systematically evaluated histological changes in liver biopsies obtained from 249
      patients with suspected DILI enrolled in the prospective, observational study
      conducted by the Drug Induced Liver Injury Network. Histological features were
      analyzed for their frequency within different clinical phenotypes of liver injury
      and to identify associations between clinical and laboratory findings and
      histological features. The most common histological patterns were acute (21%) and
      chronic hepatitis (14%), acute (9%) and chronic cholestasis (10%), and
      cholestatic hepatitis (29%). Liver histology from 128 patients presenting with
      hepatocellular injury had more severe inflammation, necrosis, and apoptosis and
      more frequently demonstrated lobular disarray, rosette formation, and hemorrhage
      than those with cholestasis. Conversely, histology of the 73 patients with
      cholestatic injury more often demonstrated bile plugs and duct paucity. Severe or
      fatal hepatic injury in 46 patients was associated with higher degrees of
      necrosis, fibrosis stage, microvesicular steatosis, and ductular reaction among
      other findings, whereas eosinophils and granulomas were found more often in those
      with milder injury. CONCLUSION: We describe an approach for evaluating liver
      histology in DILI and demonstrate numerous associations between pathological
      findings and clinical presentations that may serve as a foundation for future
      studies correlating DILI pathology with its causality and outcome.

PMID- 24037964
TI  - Ultrasound imaging of the median nerve as a prognostic factor for carpal tunnel
      decompression.
AB  - INTRODUCTION: The diagnostic value of ultrasound imaging in carpal tunnel
      syndrome is established, but reports on its prognostic value have been
      contradictory. METHODS: This investigation was an observational study of
      subjective surgical results, evaluated by symptom severity and functional status
      scales, and an ordinal scale for overall outcome, for 145 carpal tunnel
      decompressions in relation to preoperative measurement of median nerve cross
      sectional area. RESULTS: The surgical success rate was 86%. In univariate
      analyses no significant correlation existed between outcome and preoperative
      cross-sectional area, nor with preoperative nerve conduction studies or patient
      variables, except for body mass index and gender. A multivariate model including
      electrophysiological, imaging, and patient variables was moderately predictive of
      success with an area under the receiver operating characteristic curve of 0.82.
      CONCLUSIONS: Cross-sectional area alone is unlikely to be a sufficiently reliable
      predictor of outcome for use in counseling individual patients, but imaging
      results may be useful in multivariate prognostic models.

PMID- 24037965
TI  - In vitro protection by pyruvate against cadmium-induced cytotoxicity in
      hippocampal HT-22 cells.
AB  - Cadmium is a toxic metal with no biological function in higher-order mammals.
      Humans are exposed to cadmium environmental contamination and the mechanism
      underlying the cadmium's cytotoxicity is unclear. To better understand this
      mechanism, we employed murine hippocampal HT-22 cells to test the in vitro
      effects of cadmium toxicity. Our study indicated that cadmium inhibits both
      mitochondria oxidative phosphorylation and glycolysis. In turn, this causes
      depolarization of mitochondrial membrane potential, increase of superoxide
      production and decrease of ATP generation. Furthermore, we demonstrated that the
      detrimental action of cadmium in bioenergetics could be mitigated by pyruvate, an
      intermediate metabolic product. Pyruvate decreased superoxide production,
      maintained mitochondrial membrane potential, restored glycolysis, mitigated the
      decrease in cellular ATP and attenuated cadmium cytotoxicity. Our study provides
      the first evidence that pyruvate might offer promising therapy for cadmium
      poisoning.

PMID- 24037966
TI  - Use of high-sensitivity troponin assays predicts mortality in patients with
      normal conventional troponin assays on admission-insights from a meta-analysis.
AB  - BACKGROUND: Use of high-sensitivity troponin (hs-Tn) assays can detect small
      levels of myocardial damage previously undetectable with conventional troponin (c
      Tn) assays. However, prognostic utility of these hs-Tn assays in prediction of
      mortality remains unclear in the presence of nonelevated c-Tn levels on
      admission. A systematic review and meta-analysis was performed to assess
      mortality risk of patients with hs-Tn elevations in the setting of normal c-Tn
      levels. HYPOTHESIS: Patients with hs-Tn elevations with normal c-Tn levels on
      admission blood samples, drawn to rule out acute coronary syndrome (ACS), have a
      higher mortality risk than those without hs-Tn or c-Tn elevations. METHODS: A
      search was made of the PubMed, CENTRAL, EMBASE, CINAHL, EBSCO, and Web of Science
      databases. Studies evaluating patients with suspected ACS that reported mortality
      rates for those with elevated hs-Tn levels but normal c-Tn levels on admission
      were included. A random-effects model was used to pool event rates, and data were
      reported in odds ratios (95% confidence interval). RESULTS: Four studies (N =
      2033, mean age 64-75 years, 49%-70% male) revealed that nearly 32% of suspected
      ACS patients with normal c-Tn levels on admission had elevated hs-Tn levels.
      Elevated hs-Tn levels conferred a significantly higher risk of all-cause
      mortality vs normal hs-Tn levels (odds ratio: 4.35, 95% confidence interval: 2.81
      6.73, P < 0.01), with negligible heterogeneity (I(2) = 0%). CONCLUSIONS:
      Elevation of hs-Tn levels predicted a higher risk of mortality in patients with
      suspected ACS and may aid in the early identification of higher-risk patients in
      this setting. Future studies are needed to investigate further optimal management
      strategies.

PMID- 24037967
TI  - Effects of dietary prebiotics, probiotic and synbiotics on performance, caecal
      bacterial populations and caecal fermentation concentrations of broiler chickens.
AB  - BACKGROUND: In view of a worldwide attempt to restrict or ban the use of
      antibiotics as growth promoters in animal production, probiotics, prebiotics and
      combinations of both, as synbiotics, have been suggested as potential
      alternatives. In this study, the effects of a prebiotic (isomalto
      oligosaccharides, IMO), a multi-strain probiotic (consisting of 11 Lactobacillus
      strains), and a combination of these dietary additives as a synbiotic on the
      performance, caecal bacterial populations and concentrations of caecal volatile
      fatty acids and non-volatile fatty acids of broiler chickens were evaluated.
      RESULTS: Supplementation of 1g kg-1 probiotic (PRO); 5 g kg-1 prebiotic IMO
      (PRE05); 10 g kg-1 prebiotic IMO (PRE10); synbiotic consisting of 1g kg-1
      probiotic + 5 g kg-1 prebiotic IMO (SYN05); or synbiotic consisting of 1 g kg-1
      probiotic + 10 g kg-1 prebiotic IMO (SYN10) significantly (P < 0.05) improved
      weight gain of broiler chickens at 22-42 and 1-42 days of age, and feed
      conversion rate from 1 to 21, 22-42 and 1-42 days of age. The supplementation of
      probiotic (PRO), prebiotics (PRE05 and PRE10) or synbiotics (SYN05 and SYN10)
      also significantly (P < 0.05) increased the caecal populations of lactobacilli
      and bifidobacteria, and decreased the caecal Escherichia coli at 21 days of age,
      and increased the caecal VFA at 21 and 42 days of age. In all parameters studied,
      synbiotics did not show a two-fold synergistic effect, when compared to those of
      probiotic or prebiotic alone. CONCLUSION: The results of the study indicated that
      prebiotic IMO (5 g kg-1 or 10 g kg-1), probiotic and their combinations as
      synbiotics were effective in improving the performance of broiler chickens and in
      increasing the caecal beneficial bacteria and fatty acids.

PMID- 24037968
TI  - Point of care creatinine measurement for diagnosis of renal disease using a
      disposable microchip.
AB  - A point-of-care device for the determination of elevated creatinine levels in
      blood is reported. This device potentially offers a new and simple clinical
      regime for the determination of creatinine that will give huge time savings and
      removal of several steps of determination. The test employs a disposable
      prefilled microchip and the handheld Medimate Multireader(r). By optimizing the
      analytical conditions it was found that the LOD of the proposed method was 87 MUM
      creatinine, close to the normal human serum levels that are in the range of 60 to
      100 MUM. A statistical analysis of the residual shows a normal distribution,
      indicating the absence of systematic errors in the proposed method. The test can
      be used to distinguish patients with renal insufficiency (creatinine levels >100
      MUM) from healthy persons. Long-term monitoring could furthermore distinguish
      between acute renal failure and chronic kidney disease by the rate of creatinine
      concentration rise. 

PMID- 24037969
TI  - Enhancement of endothelialisation of coronary stents by laser surface
      engineering.
AB  - BACKGROUND AND OBJECTIVE: Coronary stents have been widely used in the treatment
      of coronary heart disease. However, complications have hampered the long-term
      success of the device. Bare-metal stents (BMS) have a high rate of restenosis and
      poor endothelialisation. The drug-eluting stents (DES), although dramatically
      reduce restenosis, significantly prevent endothelialisation leading to late
      thrombosis and behave the same way as BMS after drug releasing. Rapid adhesion
      and growth of endothelial cells on the stent surface is a key process for early
      vascular healing after coronary stenting which contributes to the reduction of
      major complications. Surface properties manipulate cell growth and directly
      determine the success and life-span of the implants. However, the ideal surface
      properties of coronary stents are not yet fully understood. The objective of this
      research is to understand how surface micro/nano textures and associated material
      chemistry changes generated by a laser beam affect the behavior of endothelial
      cells on bare metal 316L stents. MATERIALS AND METHODS: A high power laser beam
      was applied to modifying the surface properties of 316L coronary stent material
      and the commercial coronary stents, followed by examination of the adhesion and
      proliferation of human coronary endothelial cells that were growing on the
      surfaces. Surface properties were examined by scanning electron microscopy,
      contact angle measurement, and X-ray photoelectron spectroscopy. RESULTS: A novel
      surface with combined micro/nano features was created on stent material 316L and
      coronary stent with a specific surface chemistry. This surface gives rise to a
      threefold increase in the adhesion and eightfold increase in the proliferation of
      endothelial cells. Interestingly, such effects were only observed when the
      surface texture was produced in the nitrogen atmosphere suggesting the importance
      of the surface chemistry, including the dramatic increase of chromium nitride,
      for the interaction of endothelial cells with the material surface. This novel
      surface is also super-hydrophilic with close to zero water/cell culture fluid
      contact angles and low cytotoxicity. CONCLUSIONS: A novel surface created by
      laser surface-engineering with a combination of defined surface texture and
      surface chemistry was found beneficial for the improvement of coronary stent
      endothelialisation. The technology presented here could work with both DES and
      BMS with added benefit for the improvement of the biocompatibility of current
      coronary stents.

PMID- 24037970
TI  - Type-1 hepatorenal syndrome associated with infections in cirrhosis: natural
      history, outcome of kidney function, and survival.
AB  - Type-1 hepatorenal syndrome (HRS) is a common complication of bacterial
      infections in cirrhosis, but its natural history remains undefined. To assess the
      outcome of kidney function and survival of patients with type-1 HRS associated
      with infections, 70 patients diagnosed during a 6-year period were evaluated
      prospectively. Main outcomes were no reversibility of type-1 HRS during treatment
      of the infection and 3-month survival. Forty-seven (67%) of the 70 patients had
      no reversibility of type-1 HRS during treatment of the infection. [Correction to
      previous sentence added March 10, 2014, after first online publication: "Twenty
      three (33%)" was changed to "Forty-seven (67%)."] The main predictive factor of
      no reversibility of type-1 HRS was absence of infection resolution (no
      reversibility: 96% versus 48% in patients without and with resolution of the
      infection; P < 0.001). Independent predictive factors of no reversibility of type
      1 HRS were age, high baseline serum bilirubin, nosocomial infection, and
      reduction in serum creatinine <0.3 mg/dL at day 3 of antibiotic treatment. No
      reversibility was also associated with severity of circulatory dysfunction, as
      indicated by more marked activity of the vasoconstrictor systems. In the whole
      series, 3-month probability of survival was only 21%. Factors associated with
      poor prognosis were baseline serum bilirubin, no reversibility of type-1 HRS,
      lack of resolution of the infection, and development of septic shock after
      diagnosis of type-1 HRS. CONCLUSION: Type-1 HRS associated with infections is not
      reversible in two-thirds of patients with treatment of infection only. No
      reversibility of type-1 HRS is associated with lack of resolution of the
      infection, age, high bilirubin, and no early improvement of kidney function and
      implies a poor prognosis. These results may help advance the management of
      patients with type-1 HRS associated with infections.

PMID- 24037971
TI  - Do we have an understanding on incurred sample analyses - introspection?

PMID- 24037972
TI  - Infant and adult visual attention during an imitation demonstration.
AB  - Deferred imitation tasks have shown that manipulations at encoding can enhance
      infant learning and memory performance within an age, suggesting that brain
      maturation alone cannot fully account for all developmental changes in early
      memory abilities. The present study investigated whether changes in the focus of
      attention during learning might contribute to improving memory abilities during
      infancy. Infants aged 6, 9, and 12 months, and an adult comparison group, watched
      a video of a puppet imitation demonstration while visual behavior was recorded on
      an eye tracker. Overall, infants spent less time attending to the video than
      adults, and distributed their gaze more equally across the demonstrator and
      puppet stimulus. In contrast, adults directed their gaze primarily to the puppet.
      When infants were tested for their behavioral recall of the target actions,
      "imitators" were shown to have increased attention to the person and decreased
      attention to the background compared to "non-imitators." These results suggest
      that attention during learning is related to memory outcome and that changes in
      attention may be one mechanism by which manipulations to the learning event may
      enhance infant recall memory.

PMID- 24037973
TI  - Sleep duration and breast cancer risk: a meta-analysis of observational studies.
AB  - Studies on the association of short or long sleep duration with breast cancer
      risk have reported inconsistent results. We quantitatively assessed this
      association by conducting a meta-analysis based on the evidence from
      observational studies. In April 2013, we performed electronic searches in PubMed,
      EmBase and the Cochrane Library to identify studies examining the effect of sleep
      duration on breast cancer incidence. The odds ratio (OR) was used to measure any
      such association in a random-effects model. The analysis was further stratified
      by confounding factors that could bias the results. A total of six studies (two
      case-control and four cohort studies) involving 159,837 individuals were included
      in our meta-analysis. Our study did not show an association between either short
      or long sleep duration and breast cancer risk (short sleep duration data: pooled
      OR = 1.01, 95% confidence interval (CI) = 0.90-1.14, p = 0.853; long sleep
      duration data: pooled OR = 0.95, 95% CI = 0.86-1.04, p = 0.251). Moreover, we did
      not identify any statistically significant association between sleep duration and
      breast cancer risk in all the subgroup analyses. In conclusion, our findings
      indicate that sleep duration has no effect on breast cancer risk. 

PMID- 24037974
TI  - Maximizing the benefit of minimally invasive surgery.
AB  - Minimal invasive surgery is an excellent approach for the diagnosis and treatment
      of a wide range of thoracic disorders that previously required sternotomy or open
      thoracotomy. The notable benefits of minimal invasive surgery to patients include
      less postoperative pain, fewer operative and post-operative major complications,
      shortened hospital stay, faster recovery times, less scarring, less stress on the
      immune system, smaller incision, and for some procedures reduced operating time
      and reduced costs.

PMID- 24037975
TI  - Automated docking studies provide insights into molecular determinants of ligand
      recognition by N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside
      deacetylase (MshB).
AB  - The metal-dependent deacetylase N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D
      glucopyranoside deacetylase (MshB) catalyzes the deacetylation of N-acetyl-1-D
      myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside (GlcNAc-Ins), the committed
      step in mycothiol (MSH) biosynthesis. MSH is the thiol redox buffer used by
      mycobacteria to protect against oxidative damage and is involved in the
      detoxification of xenobiotics. As such, MshB is a target for the discovery of new
      drugs to treat tuberculosis (TB). While MshB substrate specificity and inhibitor
      activity have been probed extensively using enzyme kinetics, information
      regarding the molecular basis for the observed differences in substrate
      specificity and inhibitor activity is lacking. Herein we begin to examine the
      molecular determinants of MshB substrate specificity using automated docking
      studies with a set of known MshB substrates. Results from these studies offer
      insights into molecular recognition by MshB via identification of side chains and
      dynamic loops that may play roles in ligand binding. Additionally, results from
      these studies suggest that a hydrophobic cavity adjacent to the active site may
      be one important determinant of MshB substrate specificity. Importantly, this
      hydrophobic cavity may be advantageous for the design of MshB inhibitors with
      high affinity and specificity as potential TB drugs.

PMID- 24037976
TI  - PTEN germline mutations in patients initially tested for other hereditary cancer
      syndromes: would use of risk assessment tools reduce genetic testing?
AB  - PURPOSE: PTEN Hamartoma Tumor syndrome (PHTS) includes patients with Cowden
      syndrome or other syndromes with germline mutation of the PTEN tumor suppressor
      gene. The risk for breast, colorectal, and endometrial cancer and polyposis is
      increased, creating clinical overlap with hereditary breast and ovarian cancer
      (HBOC), Lynch syndrome (LS), and adenomatous polyposis syndromes (APS). We
      reviewed our series of patients with PHTS to determine how often testing criteria
      for these syndromes were met and how often other-gene testing was ordered before
      testing PTEN. PATIENTS AND METHODS: Patients were prospectively recruited by
      relaxed International Cowden Consortium criteria or presence of known germline
      PTEN mutation. Mutations were identified by mutation scanning/multiplex ligation
      dependent probe amplification analysis and confirmed by sequencing/quantitative
      polymerase chain reaction. Patients were excluded if they were adopted, were <18
      years of age, or if they were diagnosed with Cowden syndrome before 1998.
      Standard risk-assessment models were applied to determine whether patients met
      HBOC testing criteria, LS-relevant Amsterdam II/Bethesda 2004 criteria, or had
      adenomatous polyps. Prior probability of PTEN mutation was estimated with the
      Cleveland Clinic PTEN risk calculator. RESULTS: Of 137 PTEN mutation-positive
      adult probands, 59 (43.1%) met testing criteria for HBOC or LS. Of these, 45
      (32.8%) were first offered HBOC, LS, or APS testing. Of those who underwent APS
      testing, none of the six patients met criteria. Initial risk assessment by a
      genetics specialist was significantly associated with immediate PTEN testing in
      patients also meeting HBOC testing criteria. Using this PTEN risk assessment tool
      could have spared gene testing for 22 unlikely syndromes, at a total cost of
      $66,080. CONCLUSION: PHTS is an important differential diagnosis for patients
      referred for HBOC, LS, or APS. Risk assessment tools may help focus genetic
      analysis and aid in the interpretation of multiplex testing.

PMID- 24037977
TI  - Alopecia with endocrine therapies in patients with cancer.
AB  - BACKGROUND: Whereas the frequency of alopecia to cytotoxic chemotherapies has
      been well described, the incidence of alopecia during endocrine therapies (i.e.,
      anti-estrogens, aromatase inhibitors) has not been investigated. Endocrine agents
      are widely used in the treatment and prevention of many solid tumors, principally
      those of the breast and prostate. Adherence to these therapies is suboptimal, in
      part because of toxicities. We performed a systematic analysis of the literature
      to ascertain the incidence and risk for alopecia in patients receiving endocrine
      therapies. METHODS: An independent search of citations was conducted using the
      PubMed database for all literature as of February 2013. Phase II-III studies
      using the terms "tamoxifen," "toremifene," "raloxifene," "anastrozole,"
      "letrozole," "exemestane," "fulvestrant," "leuprolide," "flutamide,"
      "bicalutamide," "nilutamide," "fluoxymesterone," "estradiol," "octreotide,"
      "megestrol," "medroxyprogesterone acetate," "enzalutamide," and "abiraterone"
      were searched. RESULTS: Data from 19,430 patients in 35 clinical trials were
      available for analysis. Of these, 13,415 patients had received endocrine
      treatments and 6,015 patients served as controls. The incidence of all-grade
      alopecia ranged from 0% to 25%, with an overall incidence of 4.4% (95% confidence
      interval: 3.3%-5.9%). The highest incidence of all-grade alopecia was observed in
      patients treated with tamoxifen in a phase II trial (25.4%); similarly, the
      overall incidence of grade 2 alopecia by meta-analysis was highest with tamoxifen
      (6.4%). The overall relative risk of alopecia in comparison with placebo was
      12.88 (p < .001), with selective estrogen receptor modulators having the highest
      risk. CONCLUSION: Alopecia is a common yet underreported adverse event of
      endocrine-based cancer therapies. Their long-term use heightens the importance of
      this condition on patients' quality of life. These findings are critical for
      pretherapy counseling, the identification of risk factors, and the development of
      interventions that could enhance adherence and mitigate this psychosocially
      difficult event.

PMID- 24037978
TI  - Early detection of recurrent disease by FDG-PET/CT leads to management changes in
      patients with squamous cell cancer of the head and neck.
AB  - OBJECTIVE: The objective of this study was to compare the efficacy of
      surveillance high-resolution computed tomography (HRCT) and physical
      examination/endoscopy (PE/E) with the efficacy of fluorodeoxyglucose (FDG)
      positron emission tomography (PET)/HRCT for the detection of relapse in head and
      neck squamous cell carcinoma (HNSCC) after primary treatment. METHODS: This is a
      retrospective analysis of contemporaneously performed FDG-PET/HRCT, neck HRCT,
      and PE/E in 99 curatively treated patients with HNSCC during post-therapy
      surveillance to compare performance test characteristics in the detection of
      early recurrence or second primary cancer. RESULTS: Relapse occurred in 19 of 99
      patients (20%) during a median follow-up of 21 months (range: 9-52 months).
      Median time to first PET/HRCT was 3.5 months. The median time to radiological
      recurrence was 6 months (range: 2.3-32 months). FDG-PET/HRCT detected more
      disease recurrences or second primary cancers and did so earlier than HRCT or
      PE/E. The sensitivity, specificity, and positive and negative predictive values
      for detecting locoregional and distant recurrence or second primary cancer were
      100%, 87.3%, 56.5%, and 100%, respectively, for PET/HRCT versus 61.5%, 94.9%,
      66.7%, and 93.8%, respectively, for HRCT versus 23.1%, 98.7%, 75%, and 88.6%,
      respectively, for PE/E. In 19 patients with true positive PET/HRCT findings, a
      significant change in the management of disease occurred, prompting either
      salvage or systemic therapy. Of the 14 curatively treated patients, 11 were alive
      with without disease at a median follow-up of 31.5 months. CONCLUSION: FDG
      PET/HRCT has a high sensitivity in the early detection of relapse or second
      primary cancer in patients with HNSCC, with significant management implications.
      Given improvements in therapy and changes in HNSCC biology, appropriate
      modifications in current post-therapy surveillance may be required to determine
      effective salvage or definitive therapies.

PMID- 24037979
TI  - Aiming for a better understanding and management of cancer-related fatigue.
AB  - Cancer-related fatigue (CRF) is a serious symptom of patients with cancer and
      deteriorates their daily quality of life. Whereas fatigue is a common problem in
      the general population, with a prevalence of about 30%, up to 99% of patients
      with cancer have fatigue of more intense severity. CRF is directly related to the
      biology of cancer, but it can also be caused by anticancer treatment. We reviewed
      current evidence about the potential pathophysiological mechanisms causing CRF.
      Clinical methods to determine the presence and severity of CRF and potential
      treatment options to reduce CRF will be discussed. After reading this review, the
      reader will have knowledge of the current understanding of CRF and will be able
      to give evidence-based advice to patients with CRF. 

PMID- 24037980
TI  - Current understanding and management of medullary thyroid cancer.
AB  - Medullary thyroid cancer (MTC) typically accounts for 3%-4% of all thyroid
      cancers. Although the majority of MTCs are sporadic, 20% of cases are hereditary.
      Hereditary MTC can be found in multiple endocrine neoplasia 2A or 2B or as part
      of familial MTC based on a specific germline mutation in the RET proto-oncogene.
      This article discusses the current approaches available for the diagnosis,
      evaluation, and management of patients and their family members with suspected
      MTC. The disease is predominantly managed surgically and typically requires a
      total thyroidectomy and lymph node dissection. A review of recent guidelines on
      the extent and timing of surgical excision is discussed. There are not very many
      effective systemic treatment options for MTC, but several emerging therapeutic
      targets have promise. 

PMID- 24037981
TI  - Serology indicates cytomegalovirus infection is associated with varicella-zoster
      virus reactivation.
AB  - Varicella-zoster virus (VZV) causes chickenpox after which the virus remains
      latent in neural ganglia. Subsequent reactivation episodes occur, leading mainly
      to subclinical detection of VZV, but also to the clinical entity herpes zoster.
      These reactivations are known to occur most frequently amongst immunocompromised
      individuals, but the incidence of herpes zoster is also known to increase with
      age, supposedly as a consequence of immunosenescence. Our analysis aims to
      explore associations between cytomegalovirus (CMV) infection and VZV reactivation
      by analyzing VZV-specific antibody titers as a function of age, gender, and CMV
      serostatus. The analysis was repeated on measles and parvovirus B19 antibody
      titers. At the time of the observations, measles virus circulation was virtually
      eliminated, whereas parvovirus B19 circulated at lower levels than VZV. Multiple
      linear regression analyses, using the log-transformed antibody titers, identified
      a positive association between ageing and VZV antibody titers suggesting that
      ageing increasingly stimulates VZV reactivation. CMV infection further amplified
      the positive association between ageing and the reactivation rate. A negative
      association between CMV infection and VZV antibody titers was found in young
      individuals, thereby supporting the hypothesis that CMV infection may have a
      negative effect on the number of B-cells. However, no associations between CMV
      infection and measles or parvovirus B19 antibody titers occurred, but ageing
      tended to be associated with a decrease in the antibody titer against parvovirus
      B19. The combined results thus suggest that both CMV-dependent and CMV
      independent immunosenescence occurs. This is supported by an in-depth analysis of
      VZV, measles and parvovirus B19 antibody titers.

PMID- 24037986
TI  - Pin1-mediated prolyl isomerization of Runx1 affects PU.1 expression in pre
      monocytes.
AB  - Regulation of the hematopoietic transcription factor PU.1, a member of the ETS
      family, plays a critical role in the development of blood cells and in leukemia.
      The dosage of PU.1 has been shown to cause a shift in myelomonocytic progenitor
      fate. Pin1 is a unique substrate-specific enzyme that can isomerize phospho
      Ser/Thr-Pro peptide bonds, accelerating the conformational change in its
      substrates between a cis and a trans form. Such activity has been demonstrated to
      be a tightly controlled mechanism regulating a wide variety of protein functions
      under both normal physiological and pathological conditions. We have previously
      reported that a conformational change in Runx2 induced by Pin1 is essential for
      its function in osteogenesis in vitro and in vivo. In this study, we show that
      the Pin1-mediated conformational change in Runx1 enhances its acetylation and
      stabilization and, consequently, enhances its transacting activity. The increased
      acetylation of Runx1 represses PU.1 transcription in pre-monocytes. Conversely,
      the lack of (or the inhibition of) Pin1 increases PU.1 transcription in vitro and
      in vivo in pre-monocytes and in the spleen tissue. Pin1 KO mice have an increased
      CD11b(+) /F4/80(+) cell population and F4/80 protein expression in spleen. From
      our data, we can conclude that the conformational change in Runx1 induced by Pin1
      represses PU.1 transcription in pre-monocytes and influences the commitment to
      the monocyte lineage. The dosage of PU.1 is a crucial factor in acute myeloid
      leukemia (AML), and Pin1 may thus be a useful target for controlling PU.1
      dependent hematopoiesis, as well as leukemogenesis.

PMID- 24037987
TI  - Increased cardiovascular mortality and suicide after methyl chloride exposure.
AB  - OBJECTIVES: Methyl chloride leakage from a refrigerator occurred on board an
      Icelandic fishing vessel in 1963. Many of the crew members were hospitalized due
      to various neurological symptoms and signs. The aim was to study long-term
      mortality. METHODS: This is a cohort study. Five referents were selected from
      registries of deckhands and officers matched to each crew member according to age
      and occupation. Follow-up was through record linkage of personal identifiers with
      the nation-wide mortality registry. Hazard ratios (HR) and 95% confidence
      intervals (CI) were estimated in Cox proportional hazards model. RESULTS: The
      intoxicated crew was composed of 20 deckhands and 7 officers; the reference group
      counted 100 deckhands and 35 officers. Follow-up to the end of 2010; 14 of the
      exposed deckhands and 6 of the officers had died, versus 49 deckhands and 26
      officers among the reference group. For all cardiovascular events, the HR was
      2.06 (95% CI 1.02-4.15), for acute coronary heart disease, the HR was 3.12 (95%
      CI 1.11-8.78), for cerebrovascular diseases, the HR was 5.35 (1.18-24.35), and
      for suicide, the HR was 13.76 (1.18-160.07). CONCLUSIONS: Follow-up showed
      increased mortality due to cardiovascular diseases after 47 years. The suicide
      cases had developed severe depression after the methyl chloride intoxication that
      was related to the exposure. The use of the personal identifiers and the
      population registries strengthen the study. Detailed information on risk factors
      for chronic diseases is lacking in this study; however, the matching by
      occupation renders some similarity to the groups compared in the study.

PMID- 24037988
TI  - Glucose sensing O-GlcNAcylation pathway regulates the nuclear bile acid receptor
      farnesoid X receptor (FXR).
AB  - Bile acid metabolism is intimately linked to the control of energy homeostasis
      and glucose and lipid metabolism. The nuclear receptor farnesoid X receptor (FXR)
      plays a major role in the enterohepatic cycling of bile acids, but the impact of
      nutrients on bile acid homeostasis is poorly characterized. Metabolically active
      hepatocytes cope with increases in intracellular glucose concentrations by
      directing glucose into storage (glycogen) or oxidation (glycolysis) pathways, as
      well as to the pentose phosphate shunt and the hexosamine biosynthetic pathway.
      Here we studied whether the glucose nonoxidative hexosamine biosynthetic pathway
      modulates FXR activity. Our results show that FXR interacts with and is O
      GlcNAcylated by O-GlcNAc transferase in its N-terminal AF1 domain. Increased FXR
      O-GlcNAcylation enhances FXR gene expression and protein stability in a cell type
      specific manner. High glucose concentrations increased FXR O-GlcNAcylation, hence
      its protein stability and transcriptional activity by inactivating corepressor
      complexes, which associate in a ligand-dependent manner with FXR, and increased
      FXR binding to chromatin. Finally, in vivo fasting-refeeding experiments show
      that FXR undergoes O-GlcNAcylation in fed conditions associated with increased
      direct FXR target gene expression and decreased liver bile acid content.
      CONCLUSION: FXR activity is regulated by glucose fluxes in hepatocytes through a
      direct posttranslational modification catalyzed by the glucose-sensing hexosamine
      biosynthetic pathway.

PMID- 24037989
TI  - Microfluidic chip capillary electrophoresis coupled with electrochemiluminescence
      for enantioseparation of racemic drugs using central composite design
      optimization.
AB  - Optimization based on central composite design (CCD) for enantioseparation of
      anisodamine (AN), atenolol (AT), and metoprolol (ME) in human urine was developed
      using a microfluidic chip-CE device. Coupling the flexible and wide working range
      of microfluidic chip-CE device to CCD for chiral separation of AN, AT, and ME in
      human urine, a total of 15 experiments is needed for the optimization procedure
      as compared to 75 experiments using the normal one variable at a time
      optimization. The optimum conditions obtained are found to be more robust as
      shown by the curvature effects of the interaction factors. The developed
      microfluidic chip-CE-ECL system with adjustable dilution ratios has been
      validated by satisfactory recoveries (89.5-99% for six enanotiomers) in urine
      sample analysis. The working range (0.3-600 MUM), repeatability (3.1-4.9% RSD for
      peak height and 4.0-5.2% RSD for peak area), and detection limit (0.3-0.6 MUM) of
      the method developed are found to meet the requirements for bedside monitoring of
      AN, AT, and ME in patients under critical conditions. In summary, the hyphenation
      of CCD with the microfluidic chip-CE device is shown to offer a rapid means for
      optimizing the working conditions on simultaneous separation of three racemic
      drugs using the microfluidic chip-CE device developed. 

PMID- 24037990
TI  - Visualization of the diaphragm muscle with ultrasound improves diagnostic
      accuracy of phrenic nerve conduction studies.
AB  - INTRODUCTION: Evaluation of phrenic neuropathy (PN) with phrenic nerve conduction
      studies (PNCS) is associated with false negatives. Visualization of diaphragmatic
      muscle twitch with diaphragm ultrasound (DUS) when performing PNCS may help to
      solve this problem. METHODS: We performed bilateral, simultaneous DUS-PNCS in 10
      healthy adults and 12 patients with PN. The amplitude of the diaphragm compound
      muscle action potential (CMAP) (on PNCS) and twitch (on DUS) was calculated.
      RESULTS: Control subjects had <38% side-to-side asymmetry in twitch amplitude (on
      DUS) and 53% asymmetry in phrenic CMAP (on PCNS). In the 12 patients with PN, 12
      phrenic neuropathies were detected. Three of these patients had either
      significant side-to-side asymmetry or absolute reduction in diaphragm movement
      that was not detected with PNCS. There were no cases in which the PNCS showed an
      abnormality but the DUS did not. CONCLUSIONS: The addition of DUS to PNCS
      enhances diagnostic accuracy in PN.

PMID- 24037991
TI  - Asymmetry in children's salivary cortisol and alpha-amylase in the context of
      marital conflict: links to children's emotional security and adjustment.
AB  - Recent research supports the promise of examining interactive models of
      physiological processes on children's adjustment. The present study investigates
      interactions between children's autonomic nervous system activity and
      adrenocortical functioning in the context of marital discord; specifically,
      testing models of concurrent responses proposed by Bauer et al. ([2002]
      Developmental and Behavioral Pediatrics 23:102-113) in the prediction of
      children's behavioral responses to conflict and adjustment. Asymmetry and
      symmetry in children's salivary alpha-amylase and cortisol were examined in 195
      children (M age = 8 years) in response to viewing conflict vignettes. Results
      were partially consistent with an interactive model in the context of high
      marital discord; asymmetry among higher alpha-amylase and lower cortisol related
      to higher emotional insecurity and concurrent and subsequent maladjustment. In
      contrast, patterns of symmetrical responses were related to greater maladjustment
      for children exposed to lower levels of marital discord, supporting an additive
      model. Findings support the importance of a multisystem approach to investigating
      the adaptiveness of children's physiological stress responses, while also
      highlighting the value of considering physiological responses in the context of
      family risk.

PMID- 24037992
TI  - Carboplatin pharmacokinetics in a patient receiving hemodialysis.
AB  - With refinements and advances in hemodialysis techniques, survival for patients
      with end-stage renal disease has improved significantly. To our knowledge,
      however, no prospective trials have been performed in patients receiving
      hemodialysis who are also diagnosed with cancer and are candidates for
      chemotherapy. We describe a 73-year-old man who was diagnosed with high-grade
      neuroendocrine carcinoma, metastatic to the bone and lymph nodes, and was
      undergoing hemodialysis. Although cisplatin is more commonly used in the
      treatment of metastatic neuroendocrine cancers, it may not be the best option in
      patients who suffer from renal insufficiency. Carboplatin is a second-generation,
      nonnephrotoxic platinum analog that can be hemodialyzed, although no formal
      guidelines are available regarding the dosing for patients receiving
      hemodialysis. This case describes a patient who was treated with five cycles of
      combination carboplatin 115 mg/m(2) on day 1 and etoposide 50 mg/m(2) on day 1
      and day 3 of a 28-day cycle. Dialysis was performed for 3.5 hours starting 90
      minutes after completion of carboplatin on day 1. Pharmacokinetic assessments
      were performed at 1, 2, 4, and 12 hours after chemotherapy infusion on day 1 of
      cycle 1. Total carboplatin concentrations in plasma and platinum ultrafiltrate
      were measured. The plasma concentration of free platinum at the end of the
      infusion was 31,000 ng/ml, and the area under the plasma concentration-time curve
      was 2.9 minute.mg/ml. No significant carboplatin-related toxicities were
      reported. This case report indicates that carboplatin can be safely administered
      in patients receiving hemodialysis. 

PMID- 24037993
TI  - Late morbidity leading to hospitalization among 5-year survivors of young adult
      cancer: a report of the childhood, adolescent and young adult cancer survivors
      research program.
AB  - To estimate the risk of late morbidity leading to hospitalization among young
      adult cancer 5-year survivors compared to the general population and to examine
      the long-term effects of demographic and disease-related factors on late
      morbidity, a retrospective cohort of 902 five-year survivors of young adult
      cancer diagnosed between 1981 and 1999 was identified from British Columbia (BC)
      Cancer Registry. A matched comparison group (N = 9020) was randomly selected from
      the provincial health insurance plan. All hospitalizations until the end of 2006
      were determined from the BC health insurance plan hospitalization records. The
      Poisson regression model was used to estimate the rate ratios for late morbidity
      leading to hospitalization except pregnancy after adjusting for sociodemographic
      and clinical risk factors. Overall, 455 (50.4%) survivors and 3,419 (37.9%)
      individuals in the comparison group had at least one type of late morbidity
      leading to hospitalization. The adjusted risk of this morbidity for survivors was
      1.4 times higher than for the comparison group (95% CI = 1.22-1.54). The highest
      risks were found for hospitalization due to blood disease (RR = 4.2; 95% CI =
      1.98-8.78) and neoplasm (RR = 4.3; 95% CI = 3.41-5.33). Survivors with three
      treatment modalities had three-fold higher risk of having any type of late
      morbidity (RR = 3.22; 95% CI = 2.09-4.94) than the comparators. These findings
      emphasize that young adult cancer survivors still have high risks of a wide range
      of late morbidities. 

PMID- 24037994
TI  - Isolation, purification and characterisation of selenium-containing
      polysaccharides and proteins in selenium-enriched Radix puerariae.
AB  - BACKGROUND: Selenium (Se) is an essential dietary mineral and Radix puerariae
      (RP) (the dried root of Pueraria lobata Willd.) is a botanical supplement widely
      used as a nutraceutical. Food enriched with Se provides a feasible and economic
      approach for production of organic Se compounds. However, little is known about
      Se-enriched RP and the structure of Se-containing polysaccharides and proteins
      derived from Se-enriched RP. RESULTS: The organic form of Se accounted for 82.42%
      of total content. Purification by DEAE-52 and Sephadex G-100 column
      chromatography yielded three single fractions--RP-SeP-11, RP-SeP-22 and RP-SeP-33
      -with Se contents of 0.9562 * 10-3, 0.6113 * 10-3 and 0.3827 * 10-3 g kg-1,
      respectively. RP-SeP-11 (3.5 kDa) was made of glucose, RP-SeP-22 (19.6 kDa) was
      composed of xylose and glucose, and RP-SeP-33 (97.9 kDa) was made up galactose,
      mannose and glucose. Two Se-containing proteins were obtained with Se content of
      3.175 * 10-3 and 4.328 * 10-3 g kg-1, respectively. One appeared as three
      subunits with molecular masses of 43.0, 29.0 and 17.8 kDa while the other
      appeared as two subunits with molecular masses of 43.0 and 26.3 kDa. CONCLUSION:
      The results provide a basis for promoting the utilisation of RP resources
      enriched with Se as a promising tool for the food industry and are significant
      for its contribution to Se biochemistry in plants.

PMID- 24037995
TI  - Abuse liability of flupirtine revisited: implications of spontaneous reports of
      adverse drug reactions.
AB  - Early studies suggested that the centrally acting non-opioid and non-steroidal
      analgesic flupirtine (FLP) has no potential for abuse. However, FLP's agonistic
      effects at the GABAA receptor might prime addictive behaviors, and literature
      provides some anecdotal reports on FLP abuse/dependence. To shed more light on
      this topic we acquired and evaluated data obtained from a national German
      pharmacovigilance database. We analyzed all reports of FLP abuse/dependence that
      were recorded in the database of the German Federal Institute for Drugs and
      Medical Devices (BfArM). A total of n = 48 reports of FLP abuse/dependence could
      be identified (mean age 45 years, 62.5% female). First reports were submitted to
      BfArM in 1991 with increasing numbers of annual reports from the year 2006 on.
      Mean daily FLP dosage was 805 mg (range 200-3,000 mg). Current or previous
      substance abuse/dependence was reported in 21% and 17%, respectively. Mean
      duration of FLP abuse/dependence until report to BfArM was 23 months (range 1-84
      months). Withdrawal syndromes after discontinuation of FLP were reported in n = 9
      (19%). Our findings strengthen the hypothesis that FLP features a potential to
      cause addictive behaviors. Female sex, age >40 years, and long-term FLP-treatment
      may be possible risk factors for the development of FLP abuse/dependence. 

PMID- 24037996
TI  - Development of analytical methods for the quantification of metabolites of
      lesogaberan in a MIST investigation.
AB  - Analytical methods were developed for the determination of six metabolites of
      lesogaberan to be used in quantitative determinations of metabolites according to
      the guidelines of Metabolites in Safety Testing. The gamma-amino butyric acid
      type B receptor agonist lesogaberan and its metabolites are small polar molecules
      and hydrophilic interaction liquid chromatography was found to be a suitable
      separation mode. The samples were prepared using protein precipitation and
      negative electrospray ionization tandem mass spectrometry was used for detection.
      Initially, exploratory methods for six metabolites were set up for analysis of
      human plasma samples taken after repeated administration of a high oral dose of
      lesogaberan. The purpose was to establish which metabolites were present at
      concentrations significant for further investigation. Four of the six metabolites
      were then found at clearly detectable concentrations. The analytical methods for
      these four metabolites were further elaborated and then taken through a
      qualification procedure, which showed acceptable accuracy (86-114%), precision
      (<9%) and good linearity in the range 0.03-5 umol/L. No interferences were seen
      from endogenous plasma components.

PMID- 24037997
TI  - Enhancing health promotion during rehabilitation through information-giving,
      partnership-building, and teach-back.
AB  - PURPOSE AND CONCEPTUAL FRAMEWORK: This clinical article explores how Street,
      Gordon, and Millay's framework of evidence-based communication strategies of
      information-giving and partnership-building can be used by rehabilitation nurses
      and other rehabilitation team members in their practice to help patients with
      health promotion. METHOD (INTERVENTION STRATEGIES): This clinical article gives
      practical suggestions for using the information-giving strategies of control,
      description, instructions, options, outlook, rationale, recommendations, and
      risks; and the partnership-building strategies of agreement, decision-making,
      questions, and requests to assist patients. CONCLUSION AND CLINICAL RELEVANCE:
      Combined with the teach-back method, these strategies have been shown to increase
      the likelihood that patients will lose weight, adopt a regular exercise program,
      and bring chronic illnesses such as hypertension and diabetes under control,
      which is also likely to increase patients' functional ability and independence.
      These strategies can be used by rehabilitation nurses and all members of the
      rehabilitation team in acute, sub-acute, out-patient, and in-home rehabilitation
      programs.

PMID- 24037998
TI  - Bosentan treatment is associated with improvement of right ventricular function
      and remodeling in chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND: Medical pretreatment before pulmonary endarterectomy (PEA) can
      optimize right ventricular (RV) function and may improve postoperative outcome in
      high-risk patients. Using cardiac magnetic resonance imaging (cMRI), we
      determined whether the dual endothelin-1 antagonist bosentan improves RV function
      and remodeling in patients with chronic thromboembolic pulmonary hypertension
      (CTEPH) who waited for PEA. HYPOTHESIS: We hypothesized that medical therapy
      prior to PEA will be associated with improvements in RV remodeling and function.
      METHODS: In this pilot study, 15 operable CTEPH patients were randomly assigned
      to either bosentan (n = 8) or no bosentan (n = 7, control) for 16 weeks, next to
      "best standard of care." Both before and after treatment, RV stroke volume index
      (RVSVI), RV ejection fraction (RVEF), RV mass, RV isovolumic relaxation time
      (rIVRT), leftward ventricular septal bowing (LVSB), and left ventricular ejection
      fraction (LVEF) were determined using cMRI. RESULTS: After 16 weeks, the change
      (Delta) from baseline (median [range]) in the studied cMRI parameters differed
      significantly between the bosentan group and the controls: Delta RVSVI: 6 [-4-11]
      vs 1 [-6-3] mL/m(-2) ; Delta RVEF: 8 [-10-15] vs -4 [-7-5]%; Delta RV mass: -3 [
      6--2] vs 2 [-1-3] g/m(-2) ; Delta rIVRT: -30 [-130-20] vs 10 [-30-30] msec; Delta
      LVSB: 0.03 [-0.03-0.13] vs -0.03[-0.08-0.04] cm(-1) ; and Delta LVEF: 8 [-5-17]
      vs -2 [-14-2]% (all P < 0.05). The change from baseline in mean pulmonary artery
      pressure (-11 [-17-11] vs 5 [-6-21] mm Hg, P < 0.05) and 6-minute walk distance
      (20 [3-88] vs -4 [-40-40] m, P < 0.05) also differed significantly. CONCLUSIONS:
      In CTEPH, compared with control, treatment with bosentan for 16 weeks was
      associated with a significant improvement in cMRI parameters of RV function and
      remodelling.

PMID- 24037999
TI  - Minimizing over-diagnosis in lung cancer screening.
AB  - Overestimation of the frequency and impact of over-diagnosis bias in lung cancer
      screening has contributed to long delays in implementation of lung cancer
      screening programs. Literature review reveals little evidence of substantial
      numbers of over-diagnosed non-lethal lung cancer. There is now strong evidence
      that lung cancers that would not cause symptoms or kill during normal anticipated
      survival are uncommon and mostly limited to in situ adenocarcinomas, identifiable
      as CT non-solid nodules. Prevention of overtreatment is possible within well
      constructed diagnostic algorithms.

PMID- 24038000
TI  - A surface-tethered spheroid model for functional evaluation of 3T3-L1 adipocytes.
AB  - In order to effectively treat obesity, it must be better understood at the
      cellular level with respect to metabolic state and environmental stress. However,
      current two-dimensional (2D) in vitro cell culture methods do not represent the
      in vivo adipose tissue appropriately due to the absence of complex architecture
      and cellular signaling. Conversely, 3D in vitro cultures have been reported to
      have optimal results mimicking the adipose tissue in vivo. The main aim of this
      study was to examine the efficacy of a novel conjugate of a genetically
      engineered polymer, elastin-like polypeptide (ELP) and a synthetic polymer,
      polyethyleneimine (PEI), toward creating a 3D preadipocyte culture system. We
      then used this 3D culture model to study the preadipocyte differentiation and
      adipocyte maintenance processes when subjected to various dosages of
      nutritionally relevant free fatty acids with respect to total DNA and protein
      content, cell viability, and intracellular triglyceride accumulation. Our results
      showed that 3T3-L1 preadipocytes cultured on the ELP-PEI surface formed 3D
      spheroids within 72 h, whereas the cells cultured on unmodified tissue culture
      polystyrene surfaces remained in monolayer configuration. Significant statistical
      differences were discovered between the 3D spheroid and 2D monolayer culture with
      respect to the DNA and protein content, fatty acid consumption, and triglyceride
      accumulation, indicating differences in cellular response. Results indicated that
      the 3D culture may be a more sensitive modeling technique for in vitro adipocyte
      culture and provides a platform for future evaluation of 3D in vitro adipocyte
      function.

PMID- 24038001
TI  - Comparison of inhibitory effects between acetaminophen-glutathione conjugate and
      reduced glutathione in human glutathione reductase.
AB  - Acetaminophen overdose is the most frequent cause of acute liver injury. The main
      mechanism of acetaminophen toxicity has been attributed to oxidation of
      acetaminophen. The oxidation product is very reactive and reacts with glutathione
      generating acetaminophen-glutathione conjugate (APAP-SG). Although this conjugate
      has been recognized to be generally nontoxic, we have found recently that APAP-SG
      could produce a toxic effect. Therefore, the aim of our study was to estimate the
      toxicity of purified APAP-SG by characterizing the inhibitory effect in human
      glutathione reductase (GR) and comparing that to the inhibitory effect of the
      natural inhibitor reduced glutathione. We used two types of human GR: recombinant
      and freshly purified from red blood cells. Our results show that GR was
      significantly inhibited in the presence of both APAP-SG and reduced glutathione.
      For example, the enzyme activity of recombinant and purified GR was reduced in
      the presence of 4 mm APAP-SG (with 0.5 mm glutathione disulfide) by 28% and 22%,
      respectively. The type of enzyme inhibition was observed to be competitive in the
      cases of both APAP-SG and glutathione. As glutathione inhibits GR activity in
      cells under physiological conditions, the rate of enzyme inhibition ought to be
      weaker in the case of glutathione depletion that is typical of acetaminophen
      overdose. Notably, however, enzyme activity likely remains inhibited due to the
      presence of APAP-SG, which might enhance the pro-oxidative status in the cell. We
      conclude that our finding could reflect some other pathological mechanism that
      may contribute to the toxicity of acetaminophen.

PMID- 24038002
TI  - Risk of hepatocellular carcinoma and cancers at other sites among patients
      diagnosed with chronic hepatitis B virus infection in Sweden.
AB  - Hepatitis B virus (HBV) infection is one of most common viral infections
      worldwide. While chronic HBV infection has been shown consistently to be
      associated with hepatocellular carcinoma, data on associations with cancers at
      other sites are limited. In this study a total of 10,197 patients were diagnosed
      with chronic HBV infection in Sweden, and they were retrieved from the nationwide
      Swedish Hospital Discharge Register and Outpatient Register and linked to Cancer
      Registry data. Standardized incidence ratios (SIRs) for cancers were calculated
      for these patients in comparison with the population without HBV infection. Five
      hundred sixty-seven of whom developed cancer (SIR 1.82 (95% confidence interval
      (CI) 1.67-1.97)) during the study period. The SIR for hepatocellular carcinoma in
      patients with HBV infection was 40.58 (95% CI 30.50-50.07). In addition, a total
      of seven other cancer sites/types showed increased SIRs: cancers of the upper
      aerodigestive tract, lung, kidney, skin (squamous cell carcinoma), and thyroid
      gland, and lymphoma and leukemia. The risks of non-Hodgkin lymphoma and acute
      myeloid leukemia were increased in both Swedish- and foreign-born patients with
      HBV infection. In summary, chronic HBV infection is a strong risk factor for
      hepatocellular carcinoma and also increases the risk of seven other cancers.
      These findings illustrate the need for surveillance for cancers other than
      hepatocellular carcinoma in patients with HBV infection.

PMID- 24038003
TI  - Impairment of brainstem implicit learning paradigms differentiates multiple
      system atrophy (MSA) from idiopathic Parkinson syndrome.
AB  - OBJECTIVES: Learning as measured by eyeblink classical conditioning is preserved
      in patients with idiopathic Parkinson's disease, but severely affected in
      patients with progressive supranuclear palsy. We here sought to clarify whether
      procedural learning is impaired in multiple system atrophy (MSA), and whether it
      may be helpful for the differentiation of parkinsonian syndromes. DESIGN: We
      investigated learning using (1) eyeblink classical conditioning with a delay
      (interstimulus interval 0 ms) and a trace (600 ms) paradigm and (2) a serial
      reaction time task. SETTING: Participants were recruited from academic research
      centres. PARTICIPANTS: 11 patients with MSA and 11 healthy controls. RESULTS:
      Implicit learning in eyeblink classical conditioning (acquisition of conditioned
      responses) as well as the serial reaction time task measures of implicit learning
      (reaction time change) are impaired in patients with MSA as compared with
      controls, whereas explicit learning as measured by the sequence recall of the
      serial reaction time task is relatively preserved. ANALYSIS: We hypothesise that
      the learning deficits of patients with MSA are due to lesions of cerebellar and
      connected brainstem areas. CONCLUSIONS: A retrospective synopsis of these novel
      data on patients with MSA and groups of patients with idiopathic Parkinson's
      disease and progressive supranuclear palsy studied earlier suggest that eyeblink
      classical conditioning may contribute to the early differentiation of atypical
      Parkinson syndromes from idiopathic Parkinson's disease. This hypothesis should
      be tested in a prospective trial.

PMID- 24038004
TI  - Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease:
      a retrospective case control study.
AB  - OBJECTIVES: To investigate the risk factors and prognosis associated with acute
      exacerbation (AE) in patients with rheumatoid arthritis-associated interstitial
      lung disease (RA-ILD). DESIGN: A retrospective case-control study. SETTING: A
      single academic hospital. PARTICIPANTS: 51 consecutive patients diagnosed with RA
      ILD between 1995 and 2012. All patients fulfilled the diagnostic criteria of the
      American College of Rheumatology for RA. ILD was diagnosed on the basis of
      clinical presentation, pulmonary function tests, high-resolution CT (HRCT)
      findings and lung biopsy findings. MAIN OUTCOME MEASURES: Overall survival and
      cumulative AE incidence were analysed using Kaplan-Meier method. Cox hazards
      analysis was used to determine significant variables associated with AE
      occurrence and survival status. RESULTS: A total of 11 patients (22%) developed
      AE, with an overall 1-year incidence of 2.8%. Univariate analysis revealed that
      older age at ILD diagnosis (HR 1.11; 95% CI 1.02 to 1.21; p=0.01), usual
      interstitial pneumonia (UIP) pattern on HRCT (HR 1.95; 95% CI 1.07 to 3.63;
      p=0.03) and methotrexate usage (HR 3.04; 95% CI 1.62 to 6.02; p=0.001) were
      associated with AE. Of 11 patients who developed AE during observation period, 7
      (64%) died of initial AE. In survival, AE was a prognostic factor for poor
      outcome (HR 2.47; 95% CI 1.39 to 4.56; p=0.003). CONCLUSIONS: In patients with RA
      ILD, older age at ILD diagnosis, UIP pattern on HRCT and methotrexate usage are
      associated with the development of AE. Furthermore, AE has a serious impact on
      their survival.

PMID- 24038005
TI  - Correction.

PMID- 24038006
TI  - Correction.

PMID- 24038007
TI  - The value of personalised risk information: a qualitative study of the
      perceptions of patients with prostate cancer.
AB  - OBJECTIVE: To explore the experiences of patients with prostate cancer with risk
      information and their perceptions of the value of personalised risk information
      in treatment decisions. DESIGN: A qualitative study was conducted using focus
      groups. Semistructured interviews explored participants' experiences with using
      risk information, and their perceptions of the potential value of personalised
      risk information produced by clinical prediction models. PARTICIPANTS: English
      speaking patients, ages 54-82, diagnosed with prostate cancer within the past 3
      years, residing in rural and non-rural geographic locations in Maine (USA), and
      attending prostate cancer patient support groups. SETTING: 6 focus groups were
      conducted with 27 patients; separate groups were held for patients with low-risk,
      medium-risk and high-risk disease defined by National Comprehensive Cancer
      Network guidelines. RESULTS: Several participants reported receiving risk
      information that was imprecise rather than precise, qualitative rather than
      quantitative, indirect rather than direct and focused on biomarker values rather
      than clinical outcomes. Some participants felt that personalised risk information
      could be useful in helping them make better informed decisions, but expressed
      scepticism about its value. Many participants favoured decision-making strategies
      that were heuristic-based and intuitive rather than risk-based and deliberative,
      and perceived other forms of evidence-emotions, recommendations of trusted
      physicians, personal narratives-as more reliable and valuable in treatment
      decisions. CONCLUSIONS: Patients with prostate cancer appear to have little
      experience using personalised risk information, may favour heuristic-based over
      risk-based decision-making strategies and may perceive personalised risk
      information as less valuable than other types of evidence. These decision-making
      approaches and perceptions represent potential barriers to the clinical use of
      personalised risk information. Overcoming these barriers will require providing
      patients with greater exposure to risk information, education about the nature
      and value of personalised risk information and training in deliberative decision
      making strategies. More research is needed to confirm these findings and address
      these needs.

PMID- 24038008
TI  - Representativeness and optimal use of body mass index (BMI) in the UK Clinical
      Practice Research Datalink (CPRD).
AB  - OBJECTIVES: To assess the completeness and representativeness of body mass index
      (BMI) data in the Clinical Practice Research Datalink (CPRD), and determine an
      optimal strategy for their use. DESIGN: Descriptive study. SETTING: Electronic
      healthcare records from primary care. PARTICIPANTS: A million patient random
      sample from the UK CPRD primary care database, aged >=16 years. PRIMARY AND
      SECONDARY OUTCOME MEASURES: BMI completeness in CPRD was evaluated by age, sex
      and calendar period. CPRD-based summary BMI statistics for each calendar year
      (2003-2010) were age-standardised and sex-standardised and compared with
      equivalent statistics from the Health Survey for England (HSE). RESULTS: BMI
      completeness increased over calendar time from 37% in 1990-1994 to 77% in 2005
      2011, was higher among females and increased with age. When BMI at specific time
      points was assigned based on the most recent record, calendar-year-specific mean
      BMI statistics underestimated equivalent HSE statistics by 0.75-1.1 kg/m(2).
      Restriction to those with a recent (<=3 years) BMI resulted in mean BMI estimates
      closer to HSE (<=0.28 kg/m(2) underestimation), but excluded up to 47% of
      patients. An alternative strategy of imputing up-to-date BMI based on modelled
      changes in BMI over time since the last available record also led to mean BMI
      estimates that were close to HSE (<=0.37 kg/m(2) underestimation). CONCLUSIONS:
      Completeness of BMI in CPRD increased over time and varied by age and sex. At a
      given point in time, a large proportion of the most recent BMIs are unlikely to
      reflect current BMI; consequent BMI misclassification might be reduced by
      employing model-based imputation of current BMI.

PMID- 24038009
TI  - Myocardial infarction incidence and survival by ethnic group: Scottish Health and
      Ethnicity Linkage retrospective cohort study.
AB  - OBJECTIVE: Inequalities in coronary heart disease mortality by country of birth
      are large and poorly understood. However, these data misclassify UK-born minority
      ethnic groups and provide little detail on whether excess risk is due to
      increased incidence, poorer survival or both. DESIGN: Retrospective cohort study.
      SETTING: General resident population of Scotland. PARTICIPANTS: All those
      residing in Scotland during the 2001 Census were eligible for inclusion: 2 972
      120 people were included in the analysis. The number still residing in Scotland
      at the end of the study in 2008 is not known. PRIMARY AND SECONDARY OUTCOME
      MEASURES: As specified in the analysis plan, the primary outcome measures were
      first occurrence of admission or death due to myocardial infarction and time to
      event. There were no secondary outcome measures. RESULTS: Acute myocardial
      infarction (AMI) incidence risk ratios (95% CIs) relative to white Scottish
      populations (100) were highest among Pakistani men (164.1 (142.2 to 189.2)) and
      women (153.7 (120.5, 196.1)) and lowest for men and women of Chinese (39.5 (27.1
      to 57.6) and 59.1 (38.6 to 90.7)), other white British (77 (74.2 to 79.8) and
      72.2 (69.0 to 75.5)) and other white (83.1 (75.9 to 91.0) and 79.9 (71.5 to
      89.3)) ethnic groups. Adjustment for educational qualification did not eliminate
      these differences. Cardiac intervention uptake was similar across most ethnic
      groups. Compared to white Scottish, 28-day survival did not differ by ethnicity,
      except in Pakistanis where it was better, particularly in women (0.44 (0.25 to
      0.78)), a difference not removed by adjustment for education, travel time to
      hospital or cardiac intervention uptake. CONCLUSIONS: Pakistanis have the highest
      incidence of AMI in Scotland, a country renowned for internationally high
      cardiovascular disease rates. In contrast, survival is similar or better in
      minority ethnic groups. Clinical care and policy should focus on reducing
      incidence among Pakistanis through more aggressive prevention.

PMID- 24038010
TI  - Effect of the EndoBarrier Gastrointestinal Liner on obesity and type 2 diabetes:
      protocol for systematic review and meta-analysis of clinical studies.
AB  - INTRODUCTION: Obese patients with type 2 diabetes undergoing bariatric surgery
      experience significant and lasting weight loss and improved glycaemic control.
      However, bariatric surgical procedures such as Roux-en-Y gastric bypass are
      irreversible and associated with considerable short-term and long-term risks. The
      EndoBarrier Gastrointestinal Liner or duodenal-jejunal bypass sleeve (DJBS) is a
      fully reversible procedure that has been developed to treat obesity and type 2
      diabetes. We aim to perform a systematic review and meta-analysis of safety and
      efficacy of DJBS. METHODS AND ANALYSES: A systematic review with meta-analysis
      (as per the preferred reporting items for systematic reviews and meta-analyses)
      of randomised controlled trials of the device (vs no intervention, sham and/or
      low-calorie diet) will be performed. Primary endpoints include change in body
      weight and glycated haemoglobin and safety. Secondary endpoints constitute
      changes in other glycaemic parameters and blood lipids and the proportion of
      patients discontinuing antidiabetic medication. MEDLINE, EMBASE, The Cochrane
      Library and Science Citation Index will be sought electronically along with
      manual searches. The primary meta-analysis will use random effects models due to
      an expected intertrial heterogeneity. Fixed effect meta-analysis will be executed
      to assess the impact of small trials. Dichotomous data will be analysed using
      risk difference and continuous data using weighted mean differences, both with
      95% CIs. ETHICS AND DISSEMINATION: The study will describe the impact of DJBS on
      obesity and type 2 diabetes and possibly contribute to clinical decision-making.
      The results of this study will be disseminated by peer-reviewed publication and
      scientific presentations. REGISTRATION: PROSPERO CRD42013004819.

PMID- 24038011
TI  - GPs' perspectives on the management of patients with multimorbidity: systematic
      review and synthesis of qualitative research.
AB  - OBJECTIVE: To synthesise the existing published literature on the perceptions of
      general practitioners (GPs) or their equivalent on the clinical management of
      multimorbidity and determine targets for future research that aims to improve
      clinical care in multimorbidity. DESIGN: Systematic review and metaethnographic
      synthesis of primary studies that used qualitative methods to explore GPs'
      experiences of clinical management of multimorbidity or multiple chronic
      diseases. DATA SOURCES: EMBASE, MEDLINE, CINAHL, PsycInfo, Academic Search
      Complete, SocIndex, Social Science Full Text and digital theses/online libraries
      (database inception to September 2012) to identify literature using qualitative
      methods (focus groups or interviews). REVIEW METHODS: The 7-step metaethnographic
      approach described by Noblit and Hare, which involves cross-interpretation
      between studies while preserving the context of the primary data. RESULTS: Of
      1805 articles identified, 37 were reviewed in detail and 10 were included, using
      a total of 275 GPs in 7 different countries. Four areas of difficulty specific to
      the management of multimorbidity emerged from these papers: disorganisation and
      fragmentation of healthcare; the inadequacy of guidelines and evidence-based
      medicine; challenges in delivering patient-centred care; and barriers to shared
      decision-making. A 'line of argument' was drawn which described GPs' sense of
      isolation in decision-making for multimorbid patients. CONCLUSIONS: This
      systematic review shows that the problem areas for GPs in the management of
      multimorbidity may be classified into four domains. There will be no 'one size
      fits all' intervention for multimorbidity but these domains may be useful targets
      to guide the development of interventions that will assist and improve the
      provision of care to multimorbid patients.

PMID- 24038012
TI  - Potential role of voltage-sensing phosphatases in regulation of cell structure
      through the production of PI(3,4)P2.
AB  - Voltage-sensing phosphatase, VSP, consists of the transmembrane domain, operating
      as the voltage sensor, and the cytoplasmic domain with phosphoinositide
      phosphatase activities. The voltage sensor tightly couples with the cytoplasmic
      phosphatase and membrane depolarization induces dephosphorylation of several
      species of phosphoinositides. VSP gene is conserved from urochordate to human.
      There are some diversities among VSP ortholog proteins; range of voltage of
      voltage sensor motions as well as substrate selectivity. In contrast with recent
      understandings of biophysical mechanisms of VSPs, little is known about its
      physiological roles. Here we report that chick ortholog of VSP (designated as Gg
      VSP) induces morphological feature of cell process outgrowths with round cell
      body in DF-1 fibroblasts upon its forced expression. Expression of the voltage
      sensor mutant, Gg-VSPR153Q with shifted voltage dependence to a lower voltage led
      to more frequent changes of cell morphology than the wild-type protein.
      Coexpression of PTEN that dephosphorylates PI(3,4)P2 suppressed this effect by Gg
      VSP, indicating that the increase of PI(3,4)P2 leads to changes of cell shape. In
      addition, visualization of PI(3,4)P2 with the fluorescent protein fused with the
      TAPP1-derived pleckstrin homology (PH) domain suggested that Gg-VSP influenced
      the distribution of PI(3,4)P2 . These findings raise a possibility that one of
      the VSP's functions could be to regulate cell morphology through voltage
      sensitive tuning of phosphoinositide profile.

PMID- 24038013
TI  - Nontraumatic extradural hematoma in sickle cell anemia: a rare neurological
      complication not to be missed.

PMID- 24038014
TI  - Hypothesis: cadmium explains, in part, why smoking increases the risk of
      cardiovascular disease.
AB  - INTRODUCTION: Cigarette smoking is a major risk factor for cardiovascular disease
      via acute and chronic mechanisms, some of which remain unclear. One plausible but
      untested hypothesis concerns cadmium (Cd), a component of cigarette smoke, which
      is injurious to vascular endothelial cells and is independently associated with
      cardiovascular disease. To contribute to the formulation of this hypothesis, we
      performed a meta-analysis of the available data that consisted of cross-sectional
      studies useful to formulate but not test hypotheses. METHODS: PubMed and Google
      Scholar were searched by combining the terms smoking, Cd, correlation, blood,
      human, and tobacco. Following abstract review, 10 cross-sectional studies were
      identified. We compared serum Cd levels between smokers and nonsmokers using
      standardized mean differences (SMDs) as well as correlation coefficients between
      smoking and Cd. RESULTS: The estimated overall random effects SMD in Cd between
      smokers and nonsmokers was 1.13 (95% confidence interval [CI], .70-1.56) with
      significant heterogeneity (Q = 8.6, P < .001). The estimated overall random
      effects correlation coefficient between smoking and Cd was .54 (95% CI, .30-.72)
      with significant heterogeneity (Q = 71.3, P < .01). CONCLUSIONS: Despite major
      inherent limitations of meta-analyses of cross-sectional studies, we believe that
      the data contribute to the formulation of the hypothesis that Cd explains, in
      part, why smokers have an increased risk of cardiovascular disease. Further
      research, including analytic studies designed a priori are necessary to test the
      hypothesis.

PMID- 24038015
TI  - Can we vaccinate against atherosclerosis?
AB  - A large body of evidence implicates the immune system in the pathogenesis of
      atherosclerosis. Both active and passive immunizations have been tested as
      immunomodulation strategies to confer protective effect against atherogenesis.
      This review focuses on the current knowledge of the complex role and the
      potential for immune modulation therapy via active immunization for
      atherosclerosis. 

PMID- 24038016
TI  - Targeting cholesterol crystal-induced inflammation for the secondary prevention
      of cardiovascular disease.
AB  - Cholesterol crystals are present in nascent and advanced atherosclerotic plaque.
      Under some conditions, they may enlarge and cause direct plaque trauma or trigger
      an inflammatory cascade that promotes the growth and instability of
      atherosclerotic plaque. Therapies that reduce the risk of cholesterol crystal
      formation or prevent the associated inflammatory response have the potential to
      improve the clinical outcome of patients with cardiovascular disease. Statins
      have pleiotropic effects that can reduce the size of the free cholesterol pool
      contained within atherosclerotic plaques and prevent the formation of cholesterol
      crystals. Colchicine prevents crystal-induced inflammation by virtue of its
      ability to inhibit macrophage and neutrophil function. Both statins and
      colchicine have been demonstrated to reduce the risk of cardiovascular events in
      patients with stable coronary disease. The efficacy of statins and colchicine for
      cardiovascular prevention supports the hypothesis that crystal-induced
      inflammation plays an integral role in the progression and instability of
      coronary disease. Inhibition of cholesterol crystal-induced inflammation offers a
      promising new target for the secondary prevention of cardiovascular disease. 

PMID- 24038017
TI  - Supplementation of omega-3 polyunsaturated fatty acids prevents increase in
      arterial stiffness after experimental menopause.
AB  - BACKGROUND: Menopause is associated with increased arterial stiffness, an
      independent marker of cardiovascular risk. Omega-3 polyunsaturated fatty acids
      (N3-PUFAs) are thought to have multiple cardiovascular benefits, including
      prevention of arterial stiffness. We investigated whether treatment with N3-PUFA
      prevents increase in arterial stiffness in ovariectomized rats, an animal model
      of experimental menopause. METHODS: A total of 43 Wistar rats, 2 months old, were
      divided into 3 groups, control, sham surgery, normal diet (CTRL, n = 15);
      ovariectomy, normal diet (OVX, n = 14); and ovariectomy with N3-PUFA
      supplementation (0.8 g/kg/d in daily gavages administration; OVX + O3, n = 14).
      Two months after surgery, carotid-femoral pulse wave velocity (PWV) and arterial
      blood pressure (BP) were measured by carotid and femoral cannulation. Aortic
      morphometric measurements were performed after dissection. RESULTS: Ovariectomy
      caused a significant increase in BP (P < .05), PWV (P < .0001), and elastic
      modulus (P = .001) compared to CTRL. After ovariectomy, N3-PUFA supplementation
      completely prevented increase in arterial stiffness (P < .0001 vs OVX) and BP (P
      < .05 vs OVX) and resulted in a significant increase in body weight and aortic
      thickness. CONCLUSIONS: In an experimental model of menopause, N3-PUFA
      supplementation prevents arterial stiffening and other vascular changes induced
      by ovariectomy. These results represent a therapeutic benefit of N3-PUFAs in
      prevention of postmenopausal cardiovascular disease.

PMID- 24038018
TI  - Pharmacologic therapy that simulates conditioning for cardiac
      ischemic/reperfusion injury.
AB  - Cardiovascular disease remains a leading cause of deaths due to noncommunicable
      diseases, of which ischemic heart disease forms a large percentage. The main
      therapeutic strategy to treat ischemic heart disease is reperfusion that could
      either be medical or surgical. However, reperfusion following ischemia is known
      to increase the infarct size further. Newer strategies such as ischemic
      preconditioning (IPC), ischemic postconditioning, and remote IPC have been shown
      to condition the myocardium to ischemia-reperfusion injury and thus reduce the
      final infarct size. Research over the past 3 decades has deepened our
      understanding of cellular and subcellular pathways that mediate ischemia
      reperfusion injury. This in turn has resulted in the development of several
      pharmacological agents that act as conditioning agents, which reduce the final
      myocardial infarct size following ischemia-reperfusion. This review discusses
      many of these agents, their mechanisms of action, and the animal and clinical
      evidence behind them. 

PMID- 24038019
TI  - Renin-angiotensin system blocking drugs.
AB  - The two major classes of drugs that target the RAS are the angiotensin-converting
      enzyme (ACE) inhibitors and the selective AT1 receptor blockers (ARBs). Although
      both of these drug classes target angiotensin II, the differences in their
      mechanisms of action have implications for their effects on other pathways and
      receptors that may have therapeutic implications. Both ACEIs and ARBs are
      effective antihypertensive agents that have been shown to reduce the risk of
      cardiovascular and renal events. Direct inhibition of renin -the most proximal
      aspect of the RAS -became clinically feasible from 2007 with the introduction of
      aliskiren. This latter drug has been shown to be efficacious for the management
      of hypertension. Combined therapy of direct renin-inhibitors with ACEIs or ARBs
      has been tested in some clinical situations as congestive HF and proteinuria with
      diverse results. This article tries to offer an updated review of current
      knowledge on the use of RAS blocking drugs in clinical settings. 

PMID- 24038020
TI  - Novel oral anticoagulants in cardiovascular disease.
AB  - Nonvalvular atrial fibrillation (AF) confers an increased risk of
      thromboembolism, with a 5-fold higher risk of ischemic stroke. Oral
      anticoagulation (OAC) has shown to be highly effective in preventing stroke and
      mortality compared to placebo and is also used in patients without AF for both
      treatment and prophylaxis of venous thromboembolism. The OAC halts the
      coagulation by different mechanisms. Until recently, the only option was the
      vitamin K antagonists (VKAs), but their inherent limitations have promoted the
      development of novel oral anticoagulants (NOACs), which may offer efficacious and
      safer alternatives. Patients should be carefully selected to receive the most
      suitable treatment for each one. As the VKA efficacy and safety largely rely on
      the time the patient remains within the therapeutic range, this could be a useful
      selection criterion. Bleeding remains the main complication of all OACs. Although
      clinical trials of stroke prevention in AF have shown a significant reduction in
      hemorrhagic stroke and intracranial bleeding with the NOACs, as prescriptions are
      increasing, clinicians need to be prepared to accurate management of bleeding
      complications. Withholding the drug is usually enough for most cases of mild
      bleeding, but in patients with major, life-threatening bleeding, other measures,
      such as fluid replacement and blood transfusion, might be necessary while waiting
      for specific reversal agents that may reach the market soon. In case of acute
      bleeding, the accurate estimation of anticoagulant effect could also be needed,
      but the currently available coagulation tests only offer a qualitative measure.
      While awaiting long-term safety data, the choice between all these available
      therapies should be based on patient preferences, compliance, and ease of
      administration as well as on local factors affecting cost-effectiveness. But the
      increasing variety of therapeutic options when chronic OAC is needed can only
      improve the provided health care. 

PMID- 24038021
TI  - Reply: To PMID 23389758.

PMID- 24038022
TI  - Loss of quiescence and impaired function of CD34(+)/CD38(low) cells one year
      following autologous stem cell transplantation.
AB  - Patients who have undergone autologous stem cell transplantation are subsequently
      more susceptible to chemotherapy-induced bone marrow toxicity. In the present
      study, bone marrow primitive progenitor cells were examined one year after
      autologous stem cell transplantation and compared with normal bone marrow and
      mobilized peripheral blood stem cells. Post-transplantation bone marrow contained
      a significantly lower percentage of quiescent cells in the CD34(+)/CD38(low)
      fraction compared to normal bone marrow. In addition, we observed a strong
      decrease in stem cell/primitive progenitor frequency in post-transplantation
      CD34(+) cells as defined by long-term culture assays. Measurement of the levels
      of reactive oxygen species by flow cytometry revealed comparable levels in post
      transplantation and normal bone marrow CD34(+)/CD38(low) cells, while
      significantly higher levels of reactive oxygen species were observed in
      CD34(+)/CD38(high) cells following autologous stem cell transplantation compared
      to normal bone marrow. Moreover, post-transplantation CD34(+) bone marrow cells
      demonstrated an increased sensitivity to buthionine sulfoximine, a trigger for
      endogenous production of reactive oxygen species. Gene expression analysis on
      CD34(+) cells revealed a set of 195 genes, including HMOX1, EGR1, FOS and SIRPA
      that are persistently down-regulated in mobilized peripheral blood cells and post
      transplantation bone marrow compared to normal bone marrow. In conclusion, our
      data indicate that the diminished regenerative capacity of bone marrow following
      autologous stem cell transplantation is possibly related to a loss of quiescence
      and a reduced tolerability to oxidative stress. 

PMID- 24038023
TI  - Multiple productive immunoglobulin heavy chain gene rearrangements in chronic
      lymphocytic leukemia are mostly derived from independent clones.
AB  - In chronic lymphocytic leukemia, usually a monoclonal disease, multiple
      productive immunoglobulin heavy chain gene rearrangements are identified
      sporadically. Prognostication of such cases based on immunoglobulin heavy
      variable gene mutational status can be problematic, especially if the different
      rearrangements have discordant mutational status. To gain insight into the
      possible biological mechanisms underlying the origin of the multiple
      rearrangements, we performed a comprehensive immunogenetic and immunophenotypic
      characterization of 31 cases with the multiple rearrangements identified in a
      cohort of 1147 patients with chronic lymphocytic leukemia. For the majority of
      cases (25/31), we provide evidence of the co-existence of at least two B
      lymphocyte clones with a chronic lymphocytic leukemia phenotype. We also
      identified clonal drifts in serial samples, likely driven by selection forces.
      More specifically, higher immunoglobulin variable gene identity to germline and
      longer complementarity determining region 3 were preferred in persistent or newly
      appearing clones, a phenomenon more pronounced in patients with stereotyped B
      cell receptors. Finally, we report that other factors, such as TP53 gene defects
      and therapy administration, influence clonal selection. Our findings are relevant
      to clonal evolution in the context of antigen stimulation and transition of
      monoclonal B-cell lymphocytosis to chronic lymphocytic leukemia. 

PMID- 24038024
TI  - Soft-tissue extramedullary multiple myeloma prognosis is significantly worse in
      comparison to bone-related extramedullary relapse.
AB  - Even in the era of new drugs, multiple myeloma patients with extramedullary
      relapse have a poor prognosis. Our goal was to analyze the frequency and outcome
      of extramedullary relapse occurring in relapsed multiple myeloma patients. In
      total, we analyzed the prognosis of 226 relapsed multiple myeloma patients
      treated between 2005 and 2008 and evaluated them for presence of extramedullary
      relapse. We found evidence of extramedullary relapse in 24% (55 of 226) of
      relapsed multiple myeloma patients. In 14% (32 of 226) of patients, the lesions
      were not adjacent to the bone, while extramedullary relapse adjacent to the bone
      was documented in 10% (23 of 226) of cases. Patients without extramedullary
      relapse had significantly longer overall survival than patients with
      extramedullary relapse (109 vs. 38 months; P<0.001). Moreover, patients with soft
      tissue-related extramedullary relapse had significantly poorer overall survival
      compared to bone-related extramedullary relapse patients (30 vs. 45 months;
      P=0.022). Also, overall survival from diagnosis was as low as five months for
      soft tissue-related extramedullary relapse patients when compared to 12 months
      overall survival for bone-related extramedullary relapse. This is the first study
      that shows a significant difference in prognosis for different types of
      extramedullary relapse. If the extramedullary myeloma infiltration was not bone
      related, overall survival after relapse was extremely short (5 months). 

PMID- 24038025
TI  - Actual prognosis during follow-up of survivors of B-cell non-Hodgkin lymphoma in
      the Netherlands.
AB  - Survival rates determined at diagnosis are often too negative for cancer
      survivors. Conditional relative survival reflects actual prognosis during follow
      up better. Data from all 54,015 patients newly diagnosed in the Netherlands with
      B-cell non-Hodgkin lymphoma during 1989-2008, aged 15-89 years (Netherlands
      Cancer Registry), were used. Five-year conditional relative survival was computed
      for every additional year of survival up to 16 years after diagnosis, according
      to entity, grade, gender, age, and Ann Arbor stage. The prognosis for survivors
      of indolent B-cell non-Hodgkin lymphoma improved slightly with each additional
      year survived up to 91%. For patients with aggressive non-Hodgkin lymphoma
      conditional relative survival improved strongly during the first year after
      diagnosis (from 48% to 68%) and gradually thereafter to 93% after 16 years. There
      were differences between morphological entities. Initial differences in
      conditional relative survival at diagnosis between groups with different disease
      stages became smaller with increasing number of years survived. Age remained a
      prognostic indicator, also after prolonged follow-up. These results help
      caregivers to plan optimal surveillance and inform patients about their actual
      prognosis during follow-up. Long-lasting excess mortality among patients with B
      cell non-Hodgkin lymphoma indicates the need for additional care long after their
      diagnosis. 

PMID- 24038026
TI  - Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis:
      results of a median 2-year follow-up of COMFORT-I.
AB  - COMFORT-I is a randomized, double-blind, placebo-controlled trial of the Janus
      kinase 1/Janus kinase 2 inhibitor ruxolitinib in 309 patients with intermediate-2
      or high-risk myelofibrosis. This analysis of COMFORT-I describes the long-term
      efficacy and safety of ruxolitinib (median follow-up, 2 years). Spleen volume was
      measured by magnetic resonance imaging, and quality of life was evaluated using
      the EORTC QLQ-C30. Overall survival was determined according to randomized
      treatment group. At the time of this analysis, 100 of 155 patients randomized to
      ruxolitinib were still receiving treatment. All patients randomized to placebo
      crossed over to ruxolitinib or discontinued within 3 months of the primary
      analysis (median time to crossover, 41 weeks). Mean spleen volume reductions in
      the ruxolitinib group were 31.6% at week 24 and 34.9% at week 96; improvements in
      quality of life measures were also maintained. Improved survival was observed for
      ruxolitinib (n=27 deaths) versus placebo (n=41 deaths) (hazard ratio=0.58; 95%
      confidence interval: 0.36, 0.95; P=0.03). The incidence of new-onset grade 3 or 4
      anemia and thrombocytopenia decreased over time to levels observed in patients
      receiving placebo. These data indicate that ruxolitinib treatment provides
      durable reductions in spleen volume and improvements in quality of life and
      suggest a continued survival advantage for ruxolitinib over placebo. 

PMID- 24038027
TI  - Polymorphism of the complement receptor 1 gene correlates with the hematologic
      response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria.
AB  - Complement blockade by eculizumab is clinically effective in hemolytic paroxysmal
      nocturnal hemoglobinuria. However, the response is variable and some patients
      remain dependent on red blood cell transfusions. In 72 patients with hemolytic
      paroxysmal nocturnal hemoglobinuria on eculizumab we tested the hypothesis that
      response may depend on genetic polymorphisms of complement-related genes. We
      found no correlation between the complement component C3 genotypes and the need
      for blood transfusions. On the other hand, we found a significant correlation
      with the HindIII polymorphism of a complement regulatory gene, the complement
      receptor 1 (CR1) gene. At this locus two co-dominant alleles are known, of which
      H (common) is associated with high expression, whereas L (rare) is associated
      with low expression of CR1 on red blood cells. Patients who still needed blood
      transfusion on eculizumab accounted for 18% of the H/H homozygotes, 33% of the
      H/L heterozygotes and 68% of the L/L homozygotes (P=0.016). Thus, patients with
      paroxysmal nocturnal hemoglobinuria who have the L/L genotype are seven times
      more likely to be sub-optimal responders to eculizumab. Both in vitro and in vivo
      we found that the CR1 HindIII genotype correlates with the abundance of
      paroxysmal nocturnal hemoglobinuria red cells that have bound C3, and with the
      kinetics of C3 binding. These results are consistent with the notion that by
      affecting C3 binding the CR1 genotype influences the response to eculizumab
      treatment, and this emerges as a novel example of pharmacogenetics. 

PMID- 24038028
TI  - Impact of promoter polymorphisms in key regulators of the intrinsic apoptosis
      pathway on the outcome of childhood acute lymphoblastic leukemia.
AB  - The introduction of multiagent treatment protocols has led to a remarkable
      increase in survival rates for children diagnosed with acute lymphoblastic
      leukemia, yet for a subpopulation of patients, resistance to chemotherapeutics
      remains an obstacle to successful treatment. Here we investigate the role of the
      mitochondrial (or intrinsic) apoptosis pathway in modulating the onset and
      outcomes of childhood acute lymphoblastic leukemia. Cell death is a highly
      regulated process that plays an essential role in regulating cell homeostasis,
      particularly in tissues with high intrinsic proliferating capacity such as the
      hematopoietic system. Following the underlying paradigm that cis-acting genetic
      variation can influence disease risk and outcomes by modulating gene expression,
      we performed a systematic analysis of the proximal promoter regions of 21 genes
      involved in apoptosis. Using gene reporter assays, we show that promoter
      variations in 11 intrinsic apoptosis genes, including ADPRT, APAF1, BCL2, BAD,
      BID, MCL1, BIRC4, BCL2L1, ENDOG, YWHAB, and YWHAQ, influence promoter activity in
      an allele-specific manner. We also show that correlated promoter variation and
      increased expression of MCL1 is associated with reduced overall survival among
      high-risk patients receiving higher doses of corticosteroid, suggesting that
      increased expression of this anti-apoptosis gene could lead to reduced cell death
      and influence treatment response in a disease- and dose-responsive manner. 

PMID- 24038030
TI  - A rapid, straightforward, and print house compatible mass fabrication method for
      integrating 3D paper-based microfluidics.
AB  - Three-dimensional (3D) paper-based microfluidics, which is featured with high
      performance and speedy determination, promise to carry out multistep sample
      pretreatment and orderly chemical reaction, which have been used for medical
      diagnosis, cell culture, environment determination, and so on with broad market
      prospect. However, there are some drawbacks in the existing fabrication methods
      for 3D paper-based microfluidics, such as, cumbersome and time-consuming device
      assembly; expensive and difficult process for manufacture; contamination caused
      by organic reagents from their fabrication process. Here, we present a simple
      printing-bookbinding method for mass fabricating 3D paper-based microfluidics.
      This approach involves two main steps: (i) wax-printing, (ii) bookbinding. We
      tested the delivery capability, diffusion rate, homogeneity and demonstrated the
      applicability of the device to chemical analysis by nitrite colorimetric assays.
      The described method is rapid (<30 s), cheap, easy to manipulate, and compatible
      with the flat stitching method that is common in a print house, making itself an
      ideal scheme for large-scale production of 3D paper-based microfluidics. 

PMID- 24038029
TI  - Thalassemic erythrocytes release microparticles loaded with hemichromes by redox
      activation of p72Syk kinase.
AB  - High counts of circulating microparticles, originated from the membrane of
      abnormal erythrocytes, have been associated with increased thrombotic risk in
      hemolytic disorders. Our studies indicate that in thalassemia intermedia patients
      the number of circulating microparticles correlates with the capability of the
      thalassemic erythrocytes to release microparticles. The microparticles are
      characteristically loaded with hemichromes formed by denatured alpha-chains. This
      finding was substantiated by the positive correlation observed in thalassemia
      intermedia patients between the amount of hemichromes measured in erythrocytes,
      their capability to release microparticles and the levels of plasma hemichromes.
      We observed that hemichromes, following their binding to the cytoplasmic domain
      of band 3, induce the formation of disulfide band 3 dimers that are subsequently
      phosphorylated by p72Syk kinase. Phosphorylation of oxidized band 3 appears to be
      relevant for the formation of large hemichromes/band 3 clusters that, in turn,
      induce local membrane instability and the release of microparticles. Proteomic
      analysis of microparticles released from thalassemia intermedia erythrocytes
      indicated that, besides hemichromes and clustered band 3, the microparticles
      contain a characteristic set of proteins that includes catalase, heat shock
      protein 70, peroxiredoxin 2 and carbonic anhydrase. High amounts of
      immunoglobulins and C3 have also been found to be associated with microparticles,
      accounting for their intense phagocytosis. The effect of p72Syk kinase inhibitors
      on the release of microparticles from thalassemia intermedia erythrocytes may
      indicate new perspectives for controlling the release of circulating
      microparticles in hemolytic anemias. 

PMID- 24038031
TI  - Applications of single kernel conventional and hyperspectral imaging near
      infrared spectroscopy in cereals.
AB  - Single kernel (SK) near infrared (NIR) reflectance and transmittance technologies
      have been developed during the last two decades for a range of cereal grain
      physical quality and chemical traits as well as detecting and predicting levels
      of toxins produced by fungi. Challenges during the development of single kernel
      near infrared (SK-NIR) spectroscopy applications are modifications of existing
      NIR technology to present single kernels for scanning as well as modifying
      reference methods for the trait of interest. Numerous applications have been
      developed, and cover almost all cereals although most have been for key traits
      including moisture, protein, starch and oil in the globally important food
      grains, i.e. maize, wheat, rice and barley. An additional benefit in developing
      SK-NIR applications has been to demonstrate the value in sorting grain infected
      with a fungus or mycotoxins such as deoxynivalenol, fumonisins and aflatoxins.
      However, there is still a need to develop cost-effective technologies for high
      speed sorting which can be used for small grain samples such as those from
      breeding programmes or commercial sorting; capable of sorting tonnes per hour.
      Development of SK-NIR technologies also includes standardisation of SK reference
      methods to analyse single kernels. For protein content, the use of the Dumas
      method would require minimal standardisation; for starch or oil content,
      considerable development would be required. SK-NIR, including the use of
      hyperspectral imaging, will improve our understanding of grain quality and the
      inherent variation in the range of a trait. In the area of food safety, this
      technology will benefit farmers, industry and consumers if it enables
      contaminated grain to be removed from the human food chain.

PMID- 24038032
TI  - Number needed to treat for time-to-event data with competing risks.
AB  - The number needed to treat is a tool often used in clinical settings to
      illustrate the effect of a treatment. It has been widely adopted in the
      communication of risks to both clinicians and non-clinicians, such as patients,
      who are better able to understand this measure than absolute risk or rate
      reductions. The concept was introduced by Laupacis, Sackett, and Roberts in 1988
      for binary data, and extended to time-to-event data by Altman and Andersen in
      1999. However, up to the present, there is no definition of the number needed to
      treat for time-to-event data with competing risks. This paper introduces such a
      definition using the cumulative incidence function and suggests non-parametric
      and semi-parametric inferential methods for right-censored time-to-event data in
      the presence of competing risks. The procedures are illustrated using the data
      from a breast cancer clinical trial.

PMID- 24038033
TI  - Complete regression of glioblastoma by mesenchymal stem cells mediated prodrug
      gene therapy simulating clinical therapeutic scenario.
AB  - Suicide gene therapy mediated by mesenchymal stem cells with their ability to
      engraft into tumors makes these therapeutic stem cells an attractive tool to
      activate prodrugs directly within the tumor mass. In this study, we evaluated the
      therapeutic efficacy of human mesenchymal stem cells derived from bone marrow and
      from adipose tissue, engineered to express the suicide gene cytosine
      deaminase::uracil phosphoribosyltransferase to treat intracerebral rat C6
      glioblastoma in a simulated clinical therapeutic scenario. Intracerebrally grown
      glioblastoma was treated by resection and subsequently with single or repeated
      intracerebral inoculations of therapeutic stem cells followed by a continuous
      intracerebroventricular delivery of 5-fluorocytosine using an osmotic pump.
      Kaplan-Meier survival curves revealed that surgical resection of the tumor
      increased the survival time of the resected animals depending on the extent of
      surgical intervention. However, direct injections of therapeutic stem cells into
      the brain tissue surrounding the postoperative resection cavity led to a curative
      outcome in a significant number of treated animals. Moreover, the continuous
      supply of therapeutic stem cells into the brain with growing glioblastoma by
      osmotic pumps together with continuous prodrug delivery also proved to be
      therapeutically efficient. We assume that observed curative therapy of
      glioblastoma by stem cell-mediated prodrug gene therapy might be caused by the
      destruction of both tumor cells and the niche where glioblastoma initiating cells
      reside. 

PMID- 24038034
TI  - Advances in understanding the expression and function of dipeptidyl peptidase 8
      and 9.
AB  - DPP8 and DPP9 are recently identified members of the dipeptidyl peptidase IV
      (DPPIV) enzyme family, which is characterized by the rare ability to cleave a
      post-proline bond two residues from the N-terminus of a substrate. DPP8 and DPP9
      have unique cellular localization patterns, are ubiquitously expressed in tissues
      and cell lines, and evidence suggests important contributions to various
      biological processes including: cell behavior, cancer biology, disease
      pathogenesis, and immune responses. Importantly, functional differences between
      these two proteins have emerged, such as DPP8 may be more associated with gut
      inflammation whereas DPP9 is involved in antigen presentation and intracellular
      signaling. Similarly, the DPP9 connections with H-Ras and SUMO1, and its role in
      AKT1 pathway downregulation provide essential insights into the molecular
      mechanisms of DPP9 action. The recent discovery of novel natural substrates of
      DPP8 and DPP9 highlights the potential role of these proteases in energy
      metabolism and homeostasis. This review focuses on the recent progress made with
      these post-proline dipeptidyl peptidases and underscores their emerging
      importance.

PMID- 24038037
TI  - Forensic analysis of online marketing for electronic nicotine delivery systems.
AB  - BACKGROUND: Electronic nicotine delivery systems (ENDS) are growing in awareness
      and use in the USA. They are currently unregulated as the Food and Drug
      Administration has yet to assert jurisdiction under its tobacco authority over
      these products, and a US Court of Appeals held they cannot be regulated as
      drugs/delivery devices if they are not marketed for a therapeutic purpose.
      Observation of the current online marketplace suggests ENDS, like some
      nutraceutical products, are being promoted using affiliate marketing techniques
      using claims concerning purported health benefits. OBJECTIVE: This study
      performed a forensic analysis to characterise the relationships between online
      ENDS affiliate advertisements and ENDS sellers, and evaluated descriptive content
      on advertisements and websites to inform future policy and regulatory efforts.
      METHODS: A purposive sampling strategy was used to identify three forms of ENDS
      advertising. Web proxy software recorded identifiable objects and their ties to
      each other. Network analysis of these ties followed, as well as analysis of
      descriptive content on advertisements and websites identified. RESULTS: The
      forensic analysis included four ENDS advertisements, two linked affiliate
      websites, and two linked seller websites, and demonstrated a multilevel
      relationship between advertisements and sellers with multiple layers of
      redirection. Descriptive analysis indicated that advertisements and affiliates,
      but not linked sellers, included smoking cessation claims. Results suggest that
      ENDS sellers may be trying to distance marketing efforts containing
      unsubstantiated claims from sales. A separate descriptive analysis of 20 ENDS
      seller web pages indicated that the use of affiliate marketing by sellers may be
      widespread. CONCLUSIONS: These findings support increased monitoring and
      regulation of ENDS marketing to prevent deceptive marketing tactics and ensure
      consumer safety.

PMID- 24038035
TI  - Pharmacokinetics of lopinavir/ritonavir and efavirenz in food insecure HIV
      infected pregnant and breastfeeding women in Tororo, Uganda.
AB  - Pregnancy and food insecurity may impact antiretroviral (ART) pharmacokinetics
      (PK), adherence and response. We sought to quantify and characterize the PK of
      lopinavir/ritonavir (LPV/r) and efavirenz (EFV) by pregnancy and nutritional
      status among HIV-infected women in Tororo, Uganda. In 2011, 62/225 ante
      partum/post-partum single dried blood spot samples DBS and 43 post-partum hair
      samples for LPV/r were derived from 116 women, 51/194 ante-/post-partum DBS and
      53 post-partum hair samples for EFV from 105 women. Eighty percent of Ugandan
      participants were severely food insecure, 26% lost weight ante-partum, and median
      BMI post-partum was only 20.2 kg/m(2) . Rich PK-data of normally nourished
      (pregnant) women and healthy Ugandans established prior information. Overall,
      drug exposure was reduced (LPV -33%, EFV -15%, ritonavir -17%) compared to well
      nourished controls (P < 0.001), attributable to decreased bioavailability.
      Pregnancy increased LPV/r clearance 68% (P < 0.001), whereas EFV clearance
      remained unchanged. Hair concentrations correlated with plasma-exposure (P <
      0.001), explaining 29% PK-variability. In conclusion, pregnancy and food
      insecurity were associated with lower ART exposures in this cohort of
      predominantly underweight women, compared to well-nourished women. Much
      variability in plasma-exposure was quantified using hair concentrations.
      Addressing malnutrition as well as ART-PK in this setting should be a priority.

PMID- 24038036
TI  - Evaluation of reported prostate cancer risk-associated SNPs from genome-wide
      association studies of various racial populations in Chinese men.
AB  - BACKGROUND: Several genome-wide association studies (GWAS) of prostate cancer
      (PCa) have identified many single nucleotide polymorphisms (SNPs) that are
      significantly associated with PCa risk in various racial groups. The objective of
      this study is to evaluate which of these SNPs are associated with PCa risk in
      Chinese men and estimate their strength of association. METHODS: All SNPs that
      were reported to be associated with PCa risk in GWAS from populations of
      European, African American, Japanese, and Chinese descent were evaluated in 1,922
      PCa cases and 2,175 controls selected from the Chinese Consortium for Prostate
      Cancer Genetics (ChinaPCa). A logistic regression analysis was used to estimate
      allelic odds ratios (ORs) of these SNPs for PCa. RESULTS: Among the 53 SNPs, 50
      were polymorphic in the Chinese population. Of which, 10 and 24 SNPs were
      significantly associated with PCa risk in Chinese men at P < 0.001 and <0.05,
      respectively. These 24 significant SNPs included 17, 5, and 2 SNPs that were
      originally discovered in European, Japanese, and Chinese descent, respectively.
      The estimated ORs ranged from 1.10 to 1.49 and the direction of association was
      consistent with previous studies. When ORs were estimated separately for PCa with
      Gleason score <=7 and >=8, a marginally significant difference in ORs was found
      only for two of the 24 SNPs (P = 0.02 and 0.04). CONCLUSION: About half of PCa
      risk-associated SNPs identified in GWAS of various populations are associated
      with PCa risk in Chinese men. Information on PCa risk-associated SNPs and their
      ORs may facilitate risk assessment of PCa risk in Chinese men.

PMID- 24038038
TI  - Quality indicators for ductal carcinoma in situ (DCIS) of the breast: development
      using a multidisciplinary delphi process and its use in monitoring population
      based treatment.
AB  - BACKGROUND AND OBJECTIVES: Evaluation of the management of DCIS poses challenges,
      as standard breast cancer outcome measures such as mortality do not apply. We
      have developed quality indicators (QIs) to measure the quality of DCIS treatment
      in Alberta, Canada. METHODS: A modified Delphi process was used to determine QIs
      in the treatment of DCIS after review of evidence-based clinical practice
      guidelines. Patients diagnosed with DCIS from 2000 to 2001 (cohort 1) and 2009
      2010 (cohort 2) were identified from the Alberta Cancer Registry and QIs were
      retrospectively abstracted. RESULTS: The expert panel developed eight QIs to
      assess the overall quality of care for DCIS patients. Five hundred eighty
      eligible patients were identified in the two cohorts. There was significant
      improvement in radiation oncology referral, radiation post lumpectomy and
      complete pathology reporting. Axillary staging significantly increased from 20%
      (axillary dissection in cohort 1) to 60% (sentinel node biopsy in cohort 2).
      Other QIs did not differ significantly. CONCLUSIONS: By developing QIs,
      performance measures for DCIS may assessed and compared over time. Although there
      have been significant improvements with pathology reporting and radiation
      oncology assessment and treatment, axillary staging rates are unexpectedly high,
      necessitating further investigation.

PMID- 24038039
TI  - Inclusion-body myositis presenting with facial diplegia.
AB  - INTRODUCTION: The hallmark clinical presentation of inclusion-body myositis (IBM)
      is slowly progressive weakness that characteristically affects the quadriceps and
      finger and wrist finger flexor muscles. Facial weakness can also occur, but it is
      typically mild and not a prominent finding. METHODS: We describe the clinical
      features, laboratory investigations, and muscle biopsy findings in a 58-year old
      man who presented with a 6-year history of marked progressive symmetrical facial
      weakness. Examination also showed shoulder abduction and hip extensor weakness.
      RESULTS: The patient's serum creatine kinase level was 655 U/L, and
      electromyography showed fibrillation potentials and myopathic motor unit
      potentials. A biopsy specimen of the left biceps muscle was pathognomonic for
      IBM. CONCLUSIONS: This patient did not have a typical presentation for IBM but
      rather fulfilled the pathological criteria for IBM. To our knowledge, facial
      diplegia has not been reported previously as a presenting manifestation of IBM.

PMID- 24038040
TI  - Proteomic profiling in incubation medium of mouse, rat and human precision-cut
      liver slices for biomarker detection regarding acute drug-induced liver injury.
AB  - Drug-induced liver injury is one of the leading causes of drug withdrawal from
      the market. In this study, we investigated the applicability of protein profiling
      of the incubation medium of human, mouse and rat precision-cut liver slices
      (PCLS) exposed to liver injury-inducing drugs for biomarker identification, using
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
      PCLS were incubated with acetaminophen (APAP), 3-acetamidophenol, diclofenac and
      lipopolysaccharide for 24-48 h. PCLS medium from all species treated with APAP
      demonstrated similar changes in protein profiles, as previously found in mouse
      urine after APAP-induced liver injury, including the same key proteins:
      superoxide dismutase 1, carbonic anhydrase 3 and calmodulin. Further analysis
      showed that the concentration of hepcidin, a hepatic iron-regulating hormone
      peptide, was reduced in PCLS medium after APAP treatment, resembling the
      decreased mouse plasma concentrations of hepcidin observed after APAP treatment.
      Interestingly, comparable results were obtained after 3-acetamidophenol
      incubation in rat and human, but not mouse PCLS. Incubation with diclofenac, but
      not with lipopolysaccharide, resulted in the same toxicity parameters as observed
      for APAP, albeit to a lesser extent. In conclusion, proteomics can be applied to
      identify potential translational biomarkers using the PCLS system.

PMID- 24038041
TI  - Changes in psychosocial work environment and depressive symptoms: a prospective
      study in junior physicians.
AB  - BACKGROUND: We examined the impact of changes in the psychosocial work
      environment on depressive symptoms in a sample of junior physicians, a high risk
      group for stress and mental disorders. METHODS: This is a three-wave prospective
      study in 417 junior physicians during their residency in German hospitals. The
      psychosocial work environment was measured by the Effort-Reward Imbalance (ERI)
      Questionnaire at Waves 1 and 2, and the depressive symptoms were assessed with
      the State-Trait Depression Scales at all three waves. Multivariate linear
      regression was applied for prospective associations between ERI across Waves 1
      and 2, and baseline-adjusted depressive symptoms at Wave 3. RESULTS: Compared
      with the ERI scores at Wave 1, at Wave 2, and mean scores between the two waves,
      the baseline-adjusted ERI change scores between the two waves showed slightly
      better statistical power, predicting depressive symptoms at Wave 3 (beta = 0.78,
      95% CI = 0.38-1.18 for increased ERI per SD, beta = 0.64, 95% CI = 0.22-1.06 for
      increased effort per SD, beta = -0.65, 95% CI = -1.06 to -0.24 for increased
      reward per SD, and beta = 0.68, 95% CI = 0.27-1.09 for increased overcommitment
      per SD). CONCLUSIONS: Negative changes in the psychosocial work environment,
      specifically increased ERI, are associated with depressive symptoms in German
      junior physicians. Reducing the non-reciprocity of working life, particularly
      improving reward at work, may have beneficial effects on prevention of mental
      health problems in the hospital workplace.

PMID- 24038043
TI  - Avoiding complacency and maintaining progress in routine immunization.
AB  - A review of estimated coverage with three doses of diphtheria, tetanus, pertussis
      vaccine (DTP3) suggests many countries will not meet the Global Immunization
      Vision and Strategy (GIVS) goal to increase national immunization coverage levels
      to at least 90% by 2010 and to sustain these levels through at least 2015. In
      fact, 42% of low-income countries have made insufficient or no progress towards
      the goal, compared to 8% of high-income countries. Despite enormous and
      increasingly successful efforts to address the global burden of vaccine
      preventable diseases and extraordinary improvements in universal childhood
      immunization, opportunities remain to improve routine immunization coverage
      globally. 

PMID- 24038042
TI  - Recovery and quality of life in patients with ruptured cerebral aneurysms.
AB  - PURPOSE: Subarachnoid hemorrhage (SAH) secondary to ruptured cerebral aneurysm is
      a common and frequently devastating condition with a high mortality and morbidity
      among survivors. The purpose of this study was to conduct a long-term follow-up
      of SAH patients, assess the changes in functional outcomes, describe quality of
      life (QOL), and determine its predictors 3.6 years after the hemorrhage. DESIGN:
      The study design is an exploratory, descriptive correlational design. METHODS:
      Results were collected from a sample of 113 SAH survivors treated in our
      institution over a 2-year period (January 2006 until December 2007). We collected
      data on early and long-term functional outcomes and compared the differences. The
      health-related QOL was measured using the Polish version of The Short Form - 36
      Health Survey Questionnaire (SF-36v2). Multivariable logistic regression was
      derived to define independent predictors of the QOL. FINDINGS: The mean follow-up
      time was 3.6 years. Sixty-six percent of patients had improvement in functional
      outcomes and among previously employed people 56% returned to work. QOL
      deteriorated in 24% of patients with the most affected dimension of Physical
      Role. Factors that predict good QOL are male gender, younger age, good
      economic/professional status, lack of physical handicaps, rehabilitation in a
      professional center, subjective improvement in health status, and absence of
      headaches or physical decline. CONCLUSIONS AND CLINICAL RELEVANCE: Recovery
      process in SAH patients is dynamic and progresses over time. Since physical
      handicaps and low economic status significantly reduce the quality of life, an
      effort should be made to provide intensive rehabilitation and to encourage SAH
      survivors to return to work.

PMID- 24038044
TI  - Role of cytopathology in cancer control in low-resource settings: sub-Saharan
      Africa's perspective.
AB  - Cancer is an emerging public health problem in Africa especially with increasing
      exposure to risky life styles, environmental carcinogens and emergence of AIDS
      associated cancers. Of the WHO estimated 7.9 million cancer-related deaths in
      2007 more than 72% occurred in the low- and middle-income countries and 80%
      presented in the late stages. To implement the WHO resolution on cancer control
      programs in these settings, feasible evidence-based interventions for prevention,
      early diagnosis and detection need to be widely introduced. Fundamental to
      appropriate cancer treatment and statistics is accurate diagnosis. In low
      resource settings, the diagnostic techniques and procedures should be reliable,
      cost-effective, simple and acceptable to patients. In addition, the required
      equipment should be affordable, requiring minimal maintenance and with readily
      available consumables. Cytology, as a simple standardized low-technology
      procedure, fulfills these criteria and is most effective in addressing the major
      components of cancer control programs in these areas. The major obstacles to its
      widespread establishment are lack of awareness and inadequate numbers of trained
      personnel compounded by sociopolitical factors, poor national planning and
      implementation. Rather than investing in new technology or alternative screening
      methods, efforts should focus on the education and training of local personnel,
      as feasible options, to improve the chances of implementing meaningful cancer
      control programs. 

PMID- 24038045
TI  - Sharing experiences and dilemmas of conducting focus group discussions on HIV and
      tuberculosis in resource-poor settings.
AB  - Focus group discussions (FGD) are gaining in popularity in research on HIV and
      tuberculosis (TB) internationally as researchers seek to understand the
      experiences, needs and perspectives of people living with TB and/or HIV as well
      as their carers within the community and health sector. Conducting FGDs in
      resource-poor settings with vulnerable participants who are living with diseases
      that are frequently stigmatised poses multiple challenges. Our approach in this
      discussion paper is to follow the research cycle to present the practical
      experience of research teams using FGDs in TB and HIV in resource-poor contexts
      in Africa and Asia in order to contribute to effective practice. The approach
      highlights dilemmas and shares effective practice for negotiating initial
      discussions with different communities, constructing sampling frames and samples,
      choosing a facilitator, encouraging discussion, ethics, translation, pitfalls and
      dissemination. We demonstrate the techniques and adaptations needed to ensure
      that FGDs provide rich, high-quality and policy-relevant data on the voices and
      perspectives of people living with HIV and TB, community groups and health
      workers within the challenges of resource-poor settings. In applying theory to
      develop good practice in FGDs across the research cycle, a critical and reflexive
      approach is needed. 

PMID- 24038046
TI  - State capacity influences on the epidemiology of neglected tropical and vector
      borne diseases in Sub-Saharan Africa.
AB  - Many neglected tropical and vector-borne diseases continue to emerge and reemerge
      in Africa where a significant number of governments have limited state capacity.
      The reasons these diseases resurface are numerous and this problem remains
      unsolved. This study contributes to existing research by examining how economic
      and sociopolitical attributes of state capacity influence the transmission of
      disease in a population. This ecological study examined relationships between
      state capacity and the epidemiology of five neglected tropical and vector-borne
      diseases in a sample of 33 African countries. Regression analyses were used to
      examine the relationships between state capacity, i.e., economic and
      sociopolitical attributes, and disease burden, incidence, prevention/control and
      mortality. Results revealed statistically significant relationships between state
      capacity and the following dependent variables: all disease-burden variables;
      insecticide-treated-nets prevention and control; and all age-related and human
      African trypanosomiasis mortalities. A broad range of effect sizes (R(2) = 0.02
      0.59) were observed and the economic and sociopolitical attributes of state
      capacity made different contributions to these effects. Future studies should
      explore the economic and sociopolitical attributes of state capacity that
      influence disease transmission by examining different populations or diseases,
      and by using different research methods. 

PMID- 24038047
TI  - Coverage and compliance to mass drug administration for lymphatic filariasis
      elimination in a district of Kerala, India.
AB  - Mass drug administration (MDA) for lymphatic filariasis elimination is a strategy
      of administering Diethylcarbamazine (DEC) tablets to all individuals above 2
      years of age annually. It has been implemented in India and Kerala since 1997. A
      high coverage is essential for interruption of transmission in four to six years
      time, which is the average reproductive life span of the adult worm. The
      objectives of the study were to estimate the coverage and compliance of MDA for
      2007 in Thiruvananthapuram district of Kerala, India; to explore the association
      of sociodemographic variables with compliance and to find the reasons for
      noncompliance to the drug. A cross-sectional survey was conducted using the
      probability proportionate to size cluster sampling technique. Three hundred
      households were selected for estimation of coverage and all individuals in these
      households, above two years of age, excluding pregnant and bedridden elderly
      patients were studied for determining compliance. Coverage was 52.3% (95% Cl
      44.3, 60.3). Compliance was 39.5% (95% Cl 34.2, 45.0). Urban coverage was
      significantly lower than rural coverage. Compliance was not significantly related
      to any sociodemographic variables, but significantly associated with who the drug
      administrator was. Major reasons for noncompliance were fear of side effects
      (30.6%) and not perceiving the need (21.2%). Alternate drug delivery strategies
      need to be implemented to improve the coverage and compliance. Targeted
      Information Education and Communication (IEC) focusing on the safety of drugs and
      the requirement of MDA, is the need of the hour. 

PMID- 24038048
TI  - Dowry deaths: a neglected public health issue in India.
AB  - This paper appraises the public health burden of mortality in India caused by the
      practice of dowry and examines the association of some demographic and socio
      economic factors with dowry deaths and dowry-related suicides. The paper is based
      on the data available on the public domains of the National Crime Records Bureau
      (NCRB), third National Family Health and Survey-2005-06, Planning Commission of
      India and Census of India 2001. In 2007, the total number of dowry deaths and
      dowry-related suicides reported in India were 8093 and 3148, respectively. There
      was a 74% increase in dowry-related deaths from1995 to 2007, while there was a
      31% increase in the reporting of dowry-related suicides. Occurrence of dowry
      deaths has significant association with some demographic and socio-economic
      variables. The data reveal that the status of women is undesirable, and the
      burden of mortality and related morbidity is enormous. There should be a national
      injury surveillance system and reliable estimates of dowry-related homicides.
      However, available information can be used to design and implement some counter
      measures to prevent dowry-related violence and deaths. The study warrants the
      undertaking of research to give insights into circumstances and triggers of such
      violence, the healthcare seeking of these victims, bottlenecks in seeking health
      care and reporting to the police. 

PMID- 24038049
TI  - Estimating the demand for health services in four poor districts of Cape Town,
      South Africa.
AB  - In South Africa, differences in healthcare demand may perpetuate inequities in
      disease incidence, morbidity and survival. This paper presents two models of
      healthcare demand: one estimating the probability of using any service, and the
      other modelling the number of visits among users. We find that use is predicted
      by gender, perceived financial situation, mental and physical health, extra
      household resources and the price of a private consultation. The number of visits
      is predicted by age, physical and mental health, extra-household resources and
      private provider quality. These findings indicate that demand is not frivolous;
      extra-household funds enable access; patients may choose not to seek care if they
      cannot afford private care; and men are less likely to seek care at the same
      level of ill-health as women. The need for funds to access care suggests that
      local public services are not fulfilling their 'safety net' function for the most
      vulnerable. Policy makers should consider whether they can target assistance to
      households without access to extra funds. Encouraging men to use services before
      an illness becomes severe may increase early identification of infectious
      diseases, improving both individual health outcomes and public health
      consequences. 

PMID- 24038050
TI  - Factors affecting snakebite mortality in north-eastern Nigeria.
AB  - Snakebite is an important cause of mortality among rural dwellers in the savannah
      region of West Africa. We conducted a retrospective review of snakebite patients
      managed by experienced medical staff at Kaltungo in north-eastern Nigeria to
      determine the cause of death. During a 36 month period there were 94 deaths among
      6687 victims (1.41%). Relative risk (RR) of mortality increased to 2.29 (95% CI
      1.35-3.89) during a period when source of antivenom became unreliable. The
      increase was not due to seasonal variation. In a logistic regression model
      predictors of mortality were new central nervous system (CNS) features (Odds
      ratio (OR) = 24.61; 95% CI 6.93-87.41) and delay from bite to hospitalization (OR
      for every 1 h delay = 1.01; 95% CI 1.00-1.02). Treatment with antivenom was
      protective (OR = 0.17; 95% CI 0.03-0.96). Relationship of anaemia and shock to
      mortality were not maintained following adjustment. Effort should be made to
      provide regionally appropriate, affordable and effective antivenoms in addition
      to enforcement of continuous regulatory control measures. Antivenoms should be
      distributed to affected areas and treatment access points of care expanded to
      communities to diminish travel time. The populations at risk should be educated
      on avoiding unnecessary delays and on prevention of bites. 

PMID- 24038051
TI  - Knowledge, attitudes and practice (KAP) regarding newborn feeding modalities in
      HIV-infected and HIV-uninfected pregnant women in sub-Saharan Africa: a
      multicentre study.
AB  - Exclusive formula feeding, exclusive breastfeeding (EBF) with early weaning or
      the administration of antiretroviral therapy to lactating mothers and/or to
      breastfed newborns may lower postnatal HIV transmission. The aim of this study
      was to assess mothers' knowledge, attitudes and practice (KAP) on lactation in
      various real-life settings in sub-Saharan Africa. A questionnaire survey
      investigating KAP with regard to breastfeeding in pregnant women of unknown
      status (Questionnaire A, 16 items) or HIV-infected women (Questionnaire B, 37
      items) was administered. Associations between newborn feeding KAP and
      demographic, socioeconomic, cultural and obstetric variables were investigated.
      From January 2007 to January 2008, 2112 pregnant women answered Questionnaire A
      in Burkina Faso, Cameroon, Chad, Tanzania, Uganda and Zambia. Most women (53.0%)
      declared EBF as the preferred feeding modality. The practice of strictly defined
      EBF in previous pregnancies was only 11.4%, which was inversely correlated with
      education and parity. Questionnaire B was answered by 225 HIV-infected pregnant
      women in Burkina Faso, Tanzania and Uganda. Knowledge about the lactation
      associated risk was associated with previous dead children. Significant
      variability was observed among collaborating sites. The introduction of fluids
      other than maternal milk within 6 months of age is common practice in sub-Saharan
      Africa, requiring intensive health education efforts if strictly defined EBF is
      to be adopted to decrease HIV postnatal transmission. Significant variation in
      newborn feeding determinants was observed. 

PMID- 24038052
TI  - Can non-monetary incentives increase health facility deliveries? The experience
      in Thyolo District, Malawi.
AB  - Attendance for intrapartum care in Thyolo District, Malawi, was studied following
      implementation of a locally valued, non-monetary incentive. The number of
      facility-based deliveries per month was compared between the fourth quarter of
      2007 and the third quarter of 2009, before and after introducing the incentive
      that included soap, a baby blanket and a traditional baby wrap. The number of
      deliveries in health facilities increased by 78% over the 2-year period. The
      increase was larger in peripheral rural facilities compared with the district
      hospital (94% vs. 38%). Locally developed incentives may lead to more women
      receiving professional maternity care in Malawi, particularly in rural areas. 

PMID- 24038053
TI  - Role of SPARC in bone remodeling and cancer-related bone metastasis.
AB  - There is a growing socioeconomic recognition that clinical bone diseases such as
      bone infections, bone tumors and osteoporotic bone loss mainly associated with
      ageing, are major issues in today's society. SPARC (secreted protein, acidic and
      rich in cysteine), a matricellular glycoprotein, may be a promising therapeutic
      target for preventing or treating bone-related diseases. In fact, SPARC is
      associated with tissue remodeling, repair, development, cell turnover, bone
      mineralization and may also participate in growth and progression of tumors,
      namely cancer-related bone metastasis. Yet, the function of SPARC in such
      biological processes is poorly understood and controversial. The main objective
      of this work is to review the current knowledge related to the activity of SPARC
      in bone remodeling, tumorigenesis, and bone metastasis. Progress in understanding
      SPARC biology may provide novel strategies for bone regeneration and the
      development of anti-angiogenic, anti-proliferative, or counter-adhesive
      treatments specifically against bone metastasis.

PMID- 24038054
TI  - Efficacy of short-term high-dose atorvastatin pretreatment in patients with acute
      coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis
      of nine randomized controlled trials.
AB  - BACKGROUND: The efficacy of short-term high-dose atorvastatin pretreatment in
      patients with acute coronary syndrome (ACS) undergoing percutaneous coronary
      intervention (PCI) remains unclear. This meta-analysis was undertaken to assess
      the efficacy of short-term high-dose atorvastatin pretreatment in patients with
      ACS undergoing PCI. HYPOTHESIS: Short-term high-dose atorvastatin pretreatment
      may be beneficial in reducing major adverse cardiac events (MACEs) and improving
      myocardial blood flow in patients with ACS undergoing PCI. METHODS: MEDLINE,
      EMBASE, and the Cochrane Central Register of Controlled Trials were
      systematically reviewed for randomized controlled trials (RCTs) published up to
      March 2013, in which short-term high-dose atorvastatin pretreatment was compared
      with control for patients with ACS undergoing PCI. The primary outcome measure
      was the incidence of MACEs at 30 days. The meta-analysis was performed with the
      fixed effect model or random-effects model according to the heterogeneity. Meta
      analysis was performed by RevMan 5.0 software (Cochrane Collaboration,
      Copenhagen, Denmark). RESULTS: Nine RCTs incorporating 952 patients met the
      inclusion criteria and were included in this meta-analysis. Short-term high-dose
      atorvastatin pretreatment significantly reduced the incidence of MACEs at 30-day
      follow-up (risk ratio [RR] 0.39, 95% confidence interval [Cl]: 0.25 to 0.61, P <
      0.001) and improved the final Thrombolysis in Myocardial Infarction (TIMI) flow
      grade (RR 1.08, 95% Cl: 1.02 to 1.14, P = 0.01) compared with controls. There
      were no significant differences in peak creatine kinase-myocardial band and high
      sensitivity C-reactive protein level post-PCI between the 2 groups, though there
      were favorable trends related to statin use. As to the safety end points, no
      significant difference was observed in elevated liver aminotransferase level
      between short-term high-dose atorvastatin pretreatment and control groups (RR
      1.36, 95% Cl: 0.67 to 2.74). CONCLUSIONS: The use of short-term high-dose
      atorvastatin pretreatment is safe and significantly improves the final TIMI flow
      grade as well as reduces the 30-day MACEs in ACS patients post-PCI. This finding
      encourages the use of short-term high-dose atorvastatin pretreatment as an
      alternative for ACS patients undergoing PCI, but more high-quality randomized
      clinical trials are still needed to confirm the long-term efficacy and safety.

PMID- 24038056
TI  - A comparison of surgical resection and radiofrequency ablation for the treatment
      of single small hepatocellular carcinoma <=2 cm.

PMID- 24038055
TI  - Biofilm responses to smooth flow fields and chemical gradients in novel
      microfluidic flow cells.
AB  - We present two novel microfluidic flow cells developed to provide reliable
      control of flow distributions and chemical gradients in biofilm studies. We
      developed a single-inlet microfluidic flow cell to support biofilm growth under a
      uniform velocity field, and a double-inlet flow cell to provide a very smooth
      transverse concentration gradient. Both flow cells consist of a layer of
      polydimethylsiloxane (PDMS) bonded to glass cover slips and were fabricated using
      the replica molding technique. We demonstrate the capabilities of the flow cells
      by quantifying flow patterns before and after growth of Pseudomonas aeruginosa
      biofilms through particle imaging velocimetry, and by evaluating concentration
      gradients within the double-inlet microfluidic flow cell. Biofilm growth
      substantially increased flow complexity by diverting flow around biomass,
      creating high- and low-velocity regions and surface friction. Under a glucose
      gradient in the double-inlet flow cell, P. aeruginosa biofilms grew in proportion
      to the local glucose concentration, producing distinct spatial patterns in
      biofilm biomass relative to the imposed glucose gradient. When biofilms were
      subjected to a ciprofloxacin gradient, spatial patterns of fractions of dead
      cells were also in proportion to the local antibiotic concentration. These
      results demonstrate that the microfluidic flow cells are suitable for quantifying
      flow complexities resulting from flow-biofilm interactions and investigating
      spatial patterns of biofilm growth under chemical gradients. These novel
      microfluidic flow cells will facilitate biofilm research that requires flow
      control and in situ imaging, particularly investigations of biofilm-environment
      interactions.

PMID- 24038057
TI  - Indications for implant removal following intra-articular calcaneal fractures and
      subsequent complications.
AB  - INTRODUCTION: Implant removal following operative calcaneal fracture treatment
      has received little attention in the literature. The aim of the current
      retrospective cohort study was to assess the indications and number of wound
      complications following calcaneal plate removal. METHODS: All consecutive adult
      patients who had their plate and screws removed following the operative treatment
      of a closed uni- or bilateral intra-articular calcaneal fracture using a
      stainless steel nonlocking calcaneal plate between 2000 and 2011 were included.
      RESULTS: In 102 patients (46% of the total number of operated calcaneal
      fractures) implants were removed. Implant removal was performed in 75 patients
      for symptomatic reasons, in 10 patients due to implant malposition and in 19
      patients because of a persistent wound infection or fistula. Following implant
      removal 17 (16%) patients had a wound complication (2 wound dehiscence, 15
      culture positive wound infections). In 6 patients (9%) a wound complications was
      seen following implant removal after uncomplicated fracture surgery. Implant
      removal for active infection or plate fistula displayed an infection rate of 8
      out of 19 (42%). CONCLUSION: Implant removal after an intra-articular calcaneal
      fracture treated with open reduction and internal fixation via an extended
      lateral approach was followed by a wound complication in 1 of every 10 patients
      without a preexisting wound infection. Infection rates were especially high in
      patients in whom the implants were removed for an active wound problem. LEVEL OF
      EVIDENCE: Level IV, retrospective case series.

PMID- 24038058
TI  - Beyond the gowers sign: measuring outcomes in Duchenne muscular dystrophy.

PMID- 24038064
TI  - Short-term alteration of nitrogen supply prior to harvest affects quality in
      hydroponic-cultivated spinach (Spinacia oleracea).
AB  - BACKGROUND: Quality-associated problems, such as excessive in planta accumulation
      of oxalate, often arise in soillessly cultivated spinach (Spinacia oleracea).
      Maintaining a higher level of ammonium (NH4+) compared to nitrate (NO3-) during
      the growth period can effectively decrease the oxalate content in hydroponically
      cultivated vegetables. However, long-term exposure to high concentrations of NH4+
      induces toxicity in plants, and thus decreases the biomass production. Short-term
      application of NH4+ before harvesting in soilless cultivation may provide an
      alternative strategy to decrease oxalate accumulation in spinach, and minimise
      the yield reduction caused by NH4+ toxicity. RESULT: The plants were pre-cultured
      in 8 mmol L-1 NO3- nutrient solution. Next, 6 days before harvest, the plants
      were transferred to a nutrient solution containing 4 mmol L-1 NO3- and 4 mmol L-1
      NH4+. This new mix clearly reduced oxalate accumulation, increased levels of
      several antioxidant compounds, and enhanced antioxidant capacity in the edible
      parts of spinach plants, but it did not affect biomass production. However, when
      the 8 mmol L-1 NO3- was shifted to either nitrogen-free, 4 mmol L-1 NH4+ or 8
      mmol L-1 NH4+ treatments, although some of the quality indexes were improved,
      yields were significantly reduced. CONCLUSIONS: Short-term alteration of nitrogen
      supply prior to harvest significantly affects quality and biomass of spinach
      plants, and we strongly recommend to simultaneously use NO3- and NH4+ in
      hydroponic cultivation, which improves vegetable quality without decreasing
      biomass production.

PMID- 24038065
TI  - The impact of interacting drugs on dispensed doses of warfarin in the Swedish
      population: A novel use of population based drug registers.
AB  - To investigate the impact of interacting drugs on the dispensed doses of warfarin
      in the Swedish population. This was a retrospective, cross-sectional population
      based register study of patients being dispensed warfarin. Warfarin doses were
      estimated in different age groups, in men and women, and in patients using
      interacting drugs. The influence of interacting drugs on the dispensed warfarin
      dose was analyzed using multiple regression. All 143,729 patients dispensed
      warfarin were analyzed. The dispensed dose of warfarin was highest in patients 30
      39 years old and decreased with age. Co-medication with carbamazepine,
      simvastatin, paracetamol, amiodarone, fluconazole, lactulose, or bezafibrate was
      associated with significant changes in dispensed warfarin doses, by +40%, -3.4%, 
      7.3%, -8.2%, -8.8%, -9.0%, and -9.7%, respectively. After adjustment for age and
      gender, sulfamethoxazole was also found to significantly alter the dispensed
      warfarin dose (-6.1%). We provide new support for the previous scarce evidence of
      interactions between warfarin and carbamazepine, bezafibrate, and lactulose.
      Initiation or discontinuation of bezafibrate or lactulose in a patient on
      warfarin should warrant close clinical monitoring. The marked increased warfarin
      requirement associated with carbamazepine use supports moving from a more
      conservative reactive towards a proactive strategy including preventive warfarin
      dose adjustments to avoid potential adverse effects. 

PMID- 24038066
TI  - Rituximab versus splenectomy in persistent or chronic adult primary immune
      thrombocytopenia: an adjusted comparison of mortality and morbidity.
AB  - Splenectomy and rituximab are both recommended as second-line treatment in immune
      thrombocytopenia (ITP), but they have never been directly compared. We compared
      their efficacy and serious adverse outcomes in a retrospective cohort of 105
      adult primary ITP patients exposed to one or other of these treatments. Primary
      outcome was composite: death from hemorrhage or from infection and
      hospitalization for bleeding or for infection. Secondary outcomes were overall
      mortality, hospitalization for bleeding, hospitalization for infection, as well
      as response and complete response (international definitions). Analyses were
      adjusted on a propensity score. Patients treated with rituximab (n = 43) were
      older and had more comorbidities than the splenectomized patients (n = 62). Mean
      follow-up was, respectively, 3 and 8.4 years. After adjustment on the propensity
      score, there was no difference between the two groups regarding the primary and
      other clinical outcomes. In the multivariate analysis, only a history of mucosal
      bleeding (HR 3.2 95% CI [1.2-8.5]) and a Charlson score >=1 (HR 4.2 95% CI [1.8
      9.6]) were associated with the primary outcome. These two factors were also
      associated with hospitalization for bleeding. As expected, response, complete
      response and maintenance rates were higher in the splenectomy group. Splenectomy
      compared with rituximab was independently associated with a response at 12 months
      (OR 4.4, 95% CI [1.7-11.8]). Then, adjusted analyses in this real-life cohort
      confirmed the better results of splenectomy compared with rituximab.

PMID- 24038067
TI  - Multi-step manipulations of PMMA submicron particles using dielectrophoresis.
AB  - A microfluidic chip for multi-step manipulations of polymethylmethacrylate
      submicron particles (PMMA-SMPs) based on dielectrophoresis (DEP) has been
      developed that includes four main functions of focusing, guiding, trapping and
      releasing the submicron particles. The structure of the DEP chip consists of a
      top electrode made of indium tin oxide (ITO), a flow chamber formed by optically
      clear adhesive (OCA) tape and bottom electrodes with different patterns for
      different purposes. The bottom electrodes can be divided into three parts: a fish
      bone type electrode array which provides the positive DEP force for focusing the
      suspended nanoparticles near the inlet in the flow chamber; the second is for
      switching and guiding the focused nanoparticles along the electrode surface to
      the target area, like a flow passing along a virtual channel; and a trapping
      electrode in the downstream for trapping and releasing the guided nanoparticles.
      According to the simulation and experimental results, nanoparticles can be
      aligned along the electrode of the focusing electrode and guided toward the
      target electrode by means of a positive DEP force between the top and bottom
      electrodes, with the effects of Brownian motion and Stokes force. In order to
      demonstrate the sequence of DEP manipulations, a PMMA-NP suspension is introduced
      to the DEP chip; the size of the PMMA-SMPs is about 300 nm. Furthermore, a
      LabVIEW program developed for sequence control of the AC signals for the multi
      step manipulations. Consequently, the DEP chip provides an excellent platform
      technology for the multi-step manipulation of submicron particles.

PMID- 24038068
TI  - Identification of preferred chemotherapeutics for combining with a CHK1
      inhibitor.
AB  - Here we report that GNE-783, a novel checkpoint kinase-1 (CHK1) inhibitor,
      enhances the activity of gemcitabine by disabling the S- and G2 cell-cycle
      checkpoints following DNA damage. Using a focused library of 51 DNA-damaging
      agents, we undertook a systematic screen using three different cell lines to
      determine which chemotherapeutics have their activity enhanced when combined with
      GNE-783. We found that GNE-783 was most effective at enhancing activity of
      antimetabolite-based DNA-damaging agents; however, there was a surprisingly wide
      range of activity within each class of agents. We, next, selected six different
      therapeutic agents and screened these in combination with GNE-783 across a panel
      of cell lines. This revealed a preference for enhanced chemopotentiation of
      select agents within tumor types, as, for instance, GNE-783 preferentially
      enhanced the activity of temozolomide only in melanoma cell lines. Additionally,
      although p53 mutant status was important for the overall response to combinations
      with some agents; our data indicate that this alone was insufficient to predict
      synergy. We finally compared the ability of a structurally related CHK1
      inhibitor, GNE-900, to enhance the in vivo activity of gemcitabine, CPT-11, and
      temozolomide in xenograft models. GNE-900 significantly enhanced activity of only
      gemcitabine in vivo, suggesting that strong chemopotentiation in vitro can
      translate into chemopotentiation in vivo. In conclusion, our results show that
      selection of an appropriate agent to combine with a CHK1 inhibitor needs to be
      carefully evaluated in the context of the genetic background and tumor type in
      which it will be used.

PMID- 24038069
TI  - Reliability of panoramic ultrasound imaging to simultaneously examine muscle size
      and quality of the medial gastrocnemius.
AB  - INTRODUCTION: In this study we examined the test-retest reliability of panoramic
      brightness-mode ultrasound (US) imaging to simultaneously measure both muscle
      size and quality from a single US image. METHODS: Sixteen healthy, recreationally
      active men (age = 20.9 +/- 2.5 years) volunteered for this investigation. Test
      retest reliability was evaluated using intraclass correlation coefficients (ICCs)
      and the standard error of measurement as a percentage of the mean (SEM%). Muscle
      size [cross-sectional area (CSA)], and muscle quality [echo intensity (EI)] of
      the medial gastrocnemius were examined on 2 separate days. RESULTS: These
      measures demonstrated acceptable reliability between assessment days with ICCs
      and SEM% of 0.914 and 0.720 and 5.830 and 3.680 for CSA and EI, respectively.
      CONCLUSIONS: These results suggest that panoramic US imaging may be a reliable
      technique for simultaneous assessment of both muscle size and quality from a
      single US scan.

PMID- 24038070
TI  - Prognostic role of epidermal growth factor receptor in head and neck cancer: a
      meta-analysis.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the predicting value of the epidermal
      growth factor receptor (EGFR) for survival in patients with head and neck cancer
      (HNC). METHODS: Data were collected from studies comparing overall survival (OS)
      or progression-free survival (PFS) in patients with higher or lower EGFR levels.
      Studies were pooled and combined hazard ratios (HRs) of EGFR for survival were
      calculated. RESULTS: A total of 68 studies involving 6,781 patients were included
      for meta-analysis. Either EGFR protein expression or gene copy number had
      prognostic value in HNC patients. EGFR overexpression could predict worse
      outcome, with HRs of 1.65 (95% CI: 1.45, 1.86) for OS and 1.27 (95% CI: 1.17,
      1.37) for PFS. Increased EGFR copy number was also associated with reduced
      survival, with HRs of 1.5 (95% CI: 1.15, 1.96) for OS and 1.35 (95% CI: 1.14,
      1.61) for PFS. Furthermore, EGFR overexpression could predict poorer OS in both
      eastern and western countries. Particularly, EGFR was considered a strong
      predictor in laryngeal squamous cell cancer (HR > 2). CONCLUSION: Elevated EGFR
      expression and gene copy number could predict poor survival in HNC patients.

PMID- 24038071
TI  - A marginal-mean ANOVA approach for analyzing multireader multicase radiological
      imaging data.
AB  - The correlated-error ANOVA method proposed by Obuchowski and Rockette (OR) has
      been a useful procedure for analyzing reader-performance outcomes, such as the
      area under the receiver-operating-characteristic curve, resulting from
      multireader multicase radiological imaging data. This approach, however, has only
      been formally derived for the test-by-reader-by-case factorial study design. In
      this paper, I show that the OR model can be viewed as a marginal-mean ANOVA
      model. Viewing the OR model within this marginal-mean ANOVA framework is the
      basis for the marginal-mean ANOVA approach, the topic of this paper. This
      approach (1) provides an intuitive motivation for the OR model, including its
      covariance-parameter constraints; (2) provides easy derivations of OR test
      statistics and parameter estimates, as well as their distributions and confidence
      intervals; and (3) allows for easy generalization of the OR procedure to other
      study designs. In particular, I show how one can easily derive OR-type analysis
      formulas for any balanced study design by following an algorithm that only
      requires an understanding of conventional ANOVA methods.

PMID- 24038072
TI  - Characterization of the human kinetic adjustment factor for the health risk
      assessment of environmental contaminants.
AB  - A default uncertainty factor of 3.16 (?10) is applied to account for
      interindividual variability in toxicokinetics when performing non-cancer risk
      assessments. Using relevant human data for specific chemicals, as WHO/IPCS
      suggests, it is possible to evaluate, and replace when appropriate, this default
      factor by quantifying chemical-specific adjustment factors for interindividual
      variability in toxicokinetics (also referred to as the human kinetic adjustment
      factor, HKAF). The HKAF has been determined based on the distributions of
      pharmacokinetic parameters (e.g., half-life, area under the curve, maximum blood
      concentration) in relevant populations. This article focuses on the current state
      of knowledge of the use of physiologically based algorithms and models in
      characterizing the HKAF for environmental contaminants. The recent modeling
      efforts on the computation of HKAF as a function of the characteristics of the
      population, chemical and its mode of action (dose metrics), as well as exposure
      scenario of relevance to the assessment are reviewed here. The results of these
      studies, taken together, suggest the HKAF varies as a function of the sensitive
      subpopulation and dose metrics of interest, exposure conditions considered
      (route, duration, and intensity), metabolic pathways involved and theoretical
      model underlying its computation. The HKAF seldom exceeded the default value of
      3.16, except in very young children (i.e., <~ 3 months) and when the parent
      compound is the toxic moiety. Overall, from a public health perspective, the
      current state of knowledge generally suggest that the default uncertainty factor
      is sufficient to account for human variability in non-cancer risk assessments of
      environmental contaminants.

PMID- 24038073
TI  - Reciprocal regulation of microRNA-122 and c-Myc in hepatocellular cancer: role of
      E2F1 and transcription factor dimerization partner 2.
AB  - c-Myc is a well-known oncogene frequently up-regulated in different malignancies,
      whereas liver-specific microRNA (miR)-122, a bona fide tumor suppressor, is down
      regulated in hepatocellular cancer (HCC). Here we explored the underlying
      mechanism of reciprocal regulation of these two genes. Real-time reverse
      transcription polymerase chain reaction (RT-PCR) and northern blot analysis
      demonstrated reduced expression of the primary, precursor, and mature miR-122 in
      c-MYC-induced HCCs compared to the benign livers, indicating transcriptional
      suppression of miR-122 upon MYC overexpression. Indeed, chromatin
      immunoprecipitation (ChIP) assay showed significantly reduced association of RNA
      polymerase II and histone H3K9Ac, markers of active chromatin, with the miR-122
      promoter in tumors relative to the c-MYC-uninduced livers, indicating
      transcriptional repression of miR-122 in c-MYC-overexpressing tumors. The ChIP
      assay also demonstrated a significant increase in c-Myc association with the miR
      122 promoter region that harbors a conserved noncanonical c-Myc binding site in
      tumors compared to the livers. Ectopic expression and knockdown studies showed
      that c-Myc indeed suppresses expression of primary and mature miR-122 in hepatic
      cells. Additionally, Hnf-3beta, a liver enriched transcription factor that
      activates miR-122 gene, was suppressed in c-MYC-induced tumors. Notably, miR-122
      also repressed c-Myc transcription by targeting transcriptional activator E2f1
      and coactivator Tfdp2, as evident from ectopic expression and knockdown studies
      and luciferase reporter assays in mouse and human hepatic cells. CONCLUSION: c
      Myc represses miR-122 gene expression by associating with its promoter and by
      down-regulating Hnf-3beta expression, whereas miR-122 indirectly inhibits c-Myc
      transcription by targeting Tfdp2 and E2f1. In essence, these results suggest a
      double-negative feedback loop between a tumor suppressor (miR-122) and an
      oncogene (c-Myc).

PMID- 24038074
TI  - The exact science of stroke thrombolysis and the quiet art of patient selection.
AB  - The science of metric-based patient stratification for intravenous thrombolysis,
      revolutionized by the landmark National Institute of Neurological Disorders and
      Stroke trial, has transformed acute ischaemic stroke therapy. Recanalization of
      an occluded artery produces tissue reperfusion that unequivocally improves
      outcome and function in patients with acute ischaemic stroke. Recanalization can
      be achieved mainly through intravenous thrombolysis, but other methods such as
      intra-arterial thrombolysis or mechanical thrombectomy can also be employed.
      Strict guidelines preclude many patients from being treated by intravenous
      thrombolysis due to the associated risks. The quiet art of informed patient
      selection by careful assessment of patient baseline factors and brain imaging
      could increase the number of eligible patients receiving intravenous
      thrombolysis. Outside of the existing eligibility criteria, patients may fall
      into therapeutic 'grey areas' and should be evaluated on a case by case basis.
      Important factors to consider include time of onset, age, and baseline blood
      glucose, blood pressure, stroke severity (as measured by National Institutes of
      Health Stroke Scale) and computer tomography changes (as measured by Alberta
      Stroke Programme Early Computed Tomography Score). Patients with traditional
      contraindications such as wake-up stroke, malignancy or dementia may have the
      potential to receive benefit from intravenous thrombolysis if they have
      favourable predictors of outcome from both clinical and imaging criteria. A
      proportion of patients experience complications or do not respond to intravenous
      thrombolysis. In these patients, other endovascular therapies or a combination of
      both may be used to provide benefit. Although an evidence-based approach to
      intravenous thrombolysis for acute ischaemic stroke is pivotal, it is imperative
      to examine those who might benefit outside of protocol-driven practice. 

PMID- 24038075
TI  - Phase dependent modulation of tremor amplitude in essential tremor through
      thalamic stimulation.
AB  - High frequency deep brain stimulation of the thalamus can help ameliorate severe
      essential tremor. Here we explore how the efficacy, efficiency and selectivity of
      thalamic deep brain stimulation might be improved in this condition. We started
      from the hypothesis that the effects of electrical stimulation on essential
      tremor may be phase dependent, and that, in particular, there are tremor phases
      at which stimuli preferentially lead to a reduction in the amplitude of tremor.
      The latter could be exploited to improve deep brain stimulation, particularly if
      tremor suppression could be reinforced by cumulative effects. Accordingly, we
      stimulated 10 patients with essential tremor and thalamic electrodes, while
      recording tremor amplitude and phase. Stimulation near the postural tremor
      frequency entrained tremor. Tremor amplitude was also modulated depending on the
      phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in
      one half of the tremor cycle reduced median tremor amplitude by ~10%, while those
      in the opposite half of the tremor cycle increased tremor amplitude by a similar
      amount. At optimal phase alignment tremor suppression reached 27%. Moreover,
      tremor amplitude showed a non-linear increase in the degree of suppression with
      successive stimuli; tremor suppression was increased threefold if a stimulus was
      preceded by four stimuli with a similar phase relationship with respect to the
      tremor, suggesting cumulative, possibly plastic, effects. The present results
      pave the way for a stimulation system that tracks tremor phase to control when
      deep brain stimulation pulses are delivered to treat essential tremor. This would
      allow treatment effects to be maximized by focussing stimulation on the optimal
      phase for suppression and by ensuring that this is repeated over many cycles so
      as to harness cumulative effects. Such a system might potentially achieve tremor
      control with far less power demand and greater specificity than current high
      frequency stimulation approaches, and may lower the risk for tolerance and
      rebound. 

PMID- 24038076
TI  - Improving and sustaining quality of child health care through IMCI training and
      supervision: experience from rural Bangladesh.
AB  - BACKGROUND: The Integrated Management of Childhood Illness (IMCI) strategy
      includes guidelines for the management of sick children at first-level
      facilities. These guidelines intend to improve quality of care by ensuring a
      complete assessment of the child's health and by providing algorithms that
      combine presenting symptoms into a set of illness classifications for management
      by IMCI-trained service providers at first-level facilities. OBJECTIVES: To
      investigate the sustainability of improvements in under-five case management by
      two cadres of first-level government service providers with different levels of
      pre-service training following implementation of IMCI training and supportive
      supervision. METHODS: Twenty first-level health facilities in the rural sub
      district of Matlab in Bangladesh were randomly assigned to IMCI intervention or
      comparison groups. Health workers in IMCI facilities received training in case
      management and monthly supportive supervision that involved observations of case
      management and reinforcement of skills by trained physicians. Health workers in
      comparison facilities were supervised according to Government of Bangladesh
      standards. Health facility surveys involving observations of case management were
      carried out at baseline (2000) and at two points (2003 and 2005) after
      implementation of IMCI in intervention facilities. FINDINGS: Improvement in the
      management of sick under-five children by IMCI trained service providers with
      only 18 months of pre-service training was equivalent to that of service
      providers with 4 years of pre-service training. The improvements in quality of
      care were sustained over a 2-year period across both cadres of providers in
      intervention facilities. CONCLUSION: IMCI training coupled with regular
      supervision can sustain improvements in the quality of child health care in first
      level health facilities, even among workers with minimal pre-service training.
      These findings can guide government policy makers and provide further evidence to
      support the scale-up of regular supervision and task shifting the management of
      sick under-five children to lower-level service providers.

PMID- 24038077
TI  - Do antenatal care interventions improve neonatal survival in India?
AB  - Although antenatal care (ANC) interventions have been in place for a long time,
      there is hardly any systematic evidence on the association between ANC
      interventions and neonatal mortality in India. The present study attempts to
      investigate the association between ANC interventions and neonatal mortality in
      India using data from the District Level Household Survey conducted in India
      during 2007-8. The ANC interventions included in the analysis are at least four
      antenatal visits, consumption of 90 or more iron-folic acid (IFA) tablets, and
      uptake of two or more tetanus toxoid (TT) injections. We have used discrete-time
      logistic regression models to investigate the association between ANC
      interventions and neonatal mortality. Risk of neonatal mortality was
      significantly lower for infants of mothers who availed four or more antenatal
      visits [odds ratio (OR): 0.69; 95% confidence interval (CI): 0.60-0.81], consumed
      90 or more IFA tablets (OR: 0.85; 95% CI: 0.73-0.99), received two or more TT
      injections (OR: 0.73; 95% CI: 0.63-0.83). When we analysed different combinations
      of antenatal visits, IFA supplementation and TT injections, TT injections
      provided the main protective effect-the risk of neonatal mortality was
      significantly lower in newborns of women who received two or more TT injections
      but did not consume 90 or more IFA tablets (OR: 0.69; 95% CI: 0.60-0.78), or who
      received two or more TT injections but did not avail four or more antenatal
      visits (OR: 0.75; 95% CI: 0.66-0.86). In the statistical model, 6% (95% CI: 4-8%)
      of the neonatal deaths in India could be attributed to a lack of at least two TT
      injections during pregnancy. Indian public health programmes must ensure that
      every pregnant woman receives two or more TT injections during antenatal visits. 

PMID- 24038079
TI  - Genetic and genomic testing in clinical practice: what you need to know.
AB  - The clinical applications of genetic testing are growing rapidly and they now
      account for a significant percentage of total laboratory testing procedures. Many
      clinicians are uncomfortable with the types and applications of genetic tests and
      the dependable resources that are available for self-education. Furthermore,
      Direct to Consumer genetic testing has presented several challenges to healthcare
      providers as consumers now have an access to tests that they may not fully
      understand and results they may act upon inappropriately. This article presents
      some of the issues and resources to help nurses navigate this changing landscape.

PMID- 24038078
TI  - The anticancer effect of PQ1 in the MMTV-PyVT mouse model.
AB  - Animal models are commonly used to analyze the mechanism of carcinogenesis as
      well as the development and screening of potent drugs. Here the transgenic strain
      FVB/N-Tg(MMTV-PyVT)634Mul/J (also known as PyVT) was used as a model system for
      measuring tumor burden, drug sensitivity, and metastasis of mammary carcinomas.
      Loss of gap junctional intercellular communication and the down regulation of
      connexin expression are characteristic of neoplastic cells. The substituted
      quinoline, 6-methoxy-8-[(3-aminopropyl)amino]-4-methyl-5-(3-trifluoromethyl
      phenyloxy)quinolone (PQ1), has been shown to restore GJIC and increase connexin
      expression in breast cancer cell lines while not affecting normal mammary cells,
      suggesting that it may provide effective anticancer treatment with less
      detrimental effects. The PyVT spontaneous mammary tumor mouse model was used to
      determine the biological and histological effects of PQ1 on tumorigenesis and
      metastasis at three stages of development: Pretumor, early tumor and late tumor
      formation. Treatment with PQ1 at all three stages of development significantly
      reduced tumor growth. PQ1 treatment further increased Cx43 expression during pre-
      and early-tumor formation, while it prevented an increase in Cx46 expression
      during late stage tumor formation. This study shows that Cx43 expression and
      neoplastic cellular growth are inversely related, but that PQ1 can alter tumor
      growth through targeting gap junction proteins to prove clinical efficacy in the
      treatment of spontaneous mammary tumors. 

PMID- 24038080
TI  - The interaction effect of effort-reward imbalance and overcommitment on
      hypertension among Chinese workers: findings from SHISO study.
AB  - BACKGROUND: No previous studies investigated the interaction of effort-reward
      imbalance (ERI) and overcommitment on blood pressure. Our aim was to investigate
      associations of ERI and overcommitment (and their interaction) with blood
      pressure and hypertension within a Chinese population. METHODS: Seven hundred
      thirty-four participants from the Stress and Health in Shenzhen Workers study
      completed a demographics, job stressor and risk factor questionnaire, and their
      blood pressure was measured by mercury sphygmomanometers. Risk factors for blood
      pressure were analyzed by multiple linear regression and risk factors for
      hypertension by Poisson regression. RESULTS: Overcommitment was associated with
      diastolic blood pressure after adjustment for confounders and ERI among men (beta
      = 0.17, P < 0.05); ERI was also associated with diastolic blood pressure and
      systolic blood pressure after adjustment for confounders and overcommitment. High
      overcommitment (PR 1.91, 95% CI 1.35-2.69), and ERI (PR = 2.47, 95% CI 1.62-3.75)
      were each associated with risk of hypertension after adjusting for confounders.
      After adjusting for ERI, the association with overcommitment was no longer
      significant (PR = 1.24, 95% CI 0.85-1.82) However, after controlling for
      overcommitment, ERI remained significantly associated with hypertension risk (PR
      = 2.38, 95% CI 1.53-3.71). When high overcommitment and high ERI was combined,
      hypertension risk was highest (adjusted PR = 2.99, 95% CI 1.82-4.91, adjusted
      synergy index 5.85). The interaction was significant when it was tested by an
      interaction term in the regression (P < 0.001). CONCLUSIONS: The interaction
      effect of overcommitment and ERI on hypertension was independent and synergistic.

PMID- 24038082
TI  - Novel molecular mechanisms of neuromuscular disease: implications for therapy.
      Abstracts of the Muscle Study Group Meeting. September 16-18, 2013. Oxford,
      United Kingdom.

PMID- 24038081
TI  - All-trans-retinoic acid ameliorates hepatic steatosis in mice by a novel
      transcriptional cascade.
AB  - Mice deficient in small heterodimer partner (SHP) are protected from diet-induced
      hepatic steatosis resulting from increased fatty acid oxidation and decreased
      lipogenesis. The decreased lipogenesis appears to be a direct consequence of very
      low expression of peroxisome proliferator-activated receptor gamma 2 (PPAR
      gamma2), a potent lipogenic transcription factor, in the SHP(-/-) liver. The
      current study focused on the identification of a SHP-dependent regulatory cascade
      that controls PPAR-gamma2 gene expression, thereby regulating hepatic fat
      accumulation. Illumina BeadChip array (Illumina, Inc., San Diego, CA) and real
      time polymerase chain reaction were used to identify genes responsible for the
      linkage between SHP and PPAR-gamma2 using hepatic RNAs isolated from SHP(-/-) and
      SHP-overexpressing mice. The initial efforts identify that hairy and enhancer of
      split 6 (Hes6), a novel transcriptional repressor, is an important mediator of
      the regulation of PPAR-gamma2 transcription by SHP. The Hes6 promoter is
      specifically activated by the retinoic acid receptor (RAR) in response to its
      natural agonist ligand, all-trans retinoic acid (atRA), and is repressed by SHP.
      Hes6 subsequently represses hepatocyte nuclear factor 4 alpha (HNF-4alpha)
      activated PPAR-gamma2 gene expression by direct inhibition of HNF-4alpha
      transcriptional activity. Furthermore, we provide evidences that atRA treatment
      or adenovirus-mediated RAR-alpha overexpression significantly reduced hepatic fat
      accumulation in obese mouse models, as observed in earlier studies, and the
      beneficial effect is achieved by the proposed transcriptional cascade.
      CONCLUSIONS: Our study describes a novel transcriptional regulatory cascade
      controlling hepatic lipid metabolism that identifies retinoic acid signaling as a
      new therapeutic approach to nonalcoholic fatty liver diseases.

PMID- 24038083
TI  - Important role for FcgammaRIIB on B lymphocytes for mucosal antigen-induced
      tolerance and Foxp3+ regulatory T cells.
AB  - FcgammaRIIB, the only FcgammaR expressed on B cells, is important in the
      maintenance of immunological tolerance to self-Ags. In this study, we
      investigated the role of FcgammaRIIB in Ag-specific CD4 T cell tolerance induced
      by mucosally administered Ag (OVA) coupled to cholera toxin B subunit (Ag/CTB) or
      given alone. We found that sublingual administration of Ag/CTB conjugate or
      intragastric administration of a >100-fold higher dose of Ag alone efficiently
      suppressed parenteral immunization-induced Ag-specific T cell proliferation and
      delayed-type hypersensitivity responses in FcgammaRIIB-expressing wild-type (WT),
      but not FcgammaRIIB(-/-), mice. Such mucosally induced tolerance (oral tolerance)
      associated with induction of Ag-specific Foxp3(+) regulatory T cells was restored
      in FcgammaRIIB(-/-) mice by adoptive transfer of either WT B cells or WT
      dendritic cells before the mucosal Ag/CTB treatment; it was even more pronounced
      in MUMT mice that received FcgammaRIIB-overexpressing B cells before treatment.
      Furthermore, cell transfer in either WT or MUMT mice of WT but not FcgammaRIIB(-/
      ) B cells pretreated for 1 h in vitro with Ag/CTB conjugate induced Ag-specific
      immunological tolerance, which was further enhanced by adoptive transfer of WT B
      cells pretreated with anti-Ag IgG immune complexed Ag/CTB. We conclude that
      FcgammaRIIB expression on B cells, in addition to dendritic cells, is important
      for mucosal induction of Ag-specific immune tolerance. 

PMID- 24038084
TI  - Pre-existing tolerance shapes the outcome of mucosal allergen sensitization in a
      murine model of asthma.
AB  - Recent published studies have highlighted the complexity of the immune response
      to allergens, and the various asthma phenotypes that arise as a result. Although
      the interplay of regulatory and effector immune cells responding to allergen
      would seem to dictate the nature of the asthmatic response, little is known
      regarding how tolerance versus reactivity to allergen occurs in the lung. The
      vast majority of mouse models study allergen encounter in naive animals, and
      therefore exclude the possibility that previous encounters with allergen may
      influence future sensitization. To address this, we studied sensitization to the
      model allergen OVA in mice in the context of pre-existing tolerance to OVA.
      Allergen sensitization by either systemic administration of OVA with aluminum
      hydroxide or mucosal administration of OVA with low-dose LPS was suppressed in
      tolerized animals. However, higher doses of LPS induced a mixed Th2 and Th17
      response to OVA in both naive and tolerized mice. Of interest, tolerized mice had
      more pronounced Th17-type inflammation than did naive mice receiving the same
      sensitization, suggesting pre-existing tolerance altered the inflammatory
      phenotype. These data show that a pre-existing tolerogenic immune response to
      allergen can affect subsequent sensitization in the lung. These findings have
      potential significance for understanding late-onset disease in individuals with
      severe asthma. 

PMID- 24038085
TI  - The p38-MSK1 signaling cascade influences cytokine production through CREB and
      C/EBP factors in human neutrophils.
AB  - Neutrophils influence innate and adaptative immunity by generating numerous
      cytokines and chemokines whose regulation largely depends on transcriptional
      activators such as NF-kappaB and C/EBP factors. In this study, we describe the
      critical involvement of CREB transcription factors (CREB1 and activating
      transcription factor-1) in this functional response as well as relevant upstream
      signaling components. Neutrophil stimulation with LPS or TNF led to the
      phosphorylation, DNA binding activity, and chemokine promoter association of
      CREB1 and activating transcription factor-1. These responses occurred downstream
      of the p38-MSK1 signaling axis, as did the phosphorylation and promoter
      association of another bZIP factor, C/EBPbeta. Conversely, inhibition of RSK1
      failed to alter the phosphorylation of either CREB1 or C/EBPbeta in neutrophils.
      From a more functional standpoint, the inhibition of p38 MAPK or MSK1 interfered
      with cytokine generation in neutrophils. Likewise, overexpression of a dominant
      negative CREB1 mutant (K-CREB) or of a point mutant (S133A) resulted in a
      decreased ability of human neutrophil-like PLB-985 cells to generate inflammatory
      cytokines (CXCL8, CCL3, CCL4, and TNF-alpha). Collectively, our data show the
      involvement of CREB1 in neutrophil cytokine production, the key role of its S133
      residue, important upstream signaling events, and the parallel activation of
      another bZIP factor. These are all potential molecular targets that could be
      exploited in the context of several chronic inflammatory diseases that
      prominently feature neutrophils and their products. 

PMID- 24038086
TI  - Cutting edge: NK cell licensing modulates adhesion to target cells.
AB  - Binding of NK cell inhibitory receptors to MHC class I (MHC-I) confers increased
      responsiveness to NK cells by a process known as NK cell licensing/education.
      Reduced MHC-I expression or a lack of inhibitory receptors for MHC-I results in
      diminished NK cell responsiveness. In this study, we evaluated the effect of
      human and mouse NK cell licensing on early stages of natural cytotoxicity.
      Unlicensed NK cells did not form as many stable conjugates with target cells. The
      reduction of NK cell conjugation to target cells was not attributed to altered
      beta2 integrin LFA-1 properties but was instead due to reduced inside-out
      signaling to LFA-1 by activating receptors. For those unlicensed NK cells that
      did form conjugates, LFA-1-dependent granule polarization was similar to that in
      licensed NK cells. Thus, licensing controls signals as proximal as inside-out
      signaling by activating receptors but not integrin outside-in signaling for
      granule polarization. 

PMID- 24038088
TI  - LAT1 is a critical transporter of essential amino acids for immune reactions in
      activated human T cells.
AB  - Activation of T cells accompanies remarkable enhancement of metabolism.
      Sufficient and continuous nutrient supply is therefore important to support
      immune reaction in T cells. However, the mechanism of the promotion of nutrient
      incorporation in activated T cells has not been elucidated. In this study, we
      show that L-type amino acid transporter 1 (LAT1) is a major transporter for
      essential amino acids into activated human T cells. CD3/CD28 stimulation in
      primary human T cells triggered dramatic induction of LAT1 expression mediated by
      NF-kappaB and AP-1. Functional disturbance of LAT1 by a specific inhibitor and by
      small interfering RNA in human T cells suppressed essential amino acid uptake and
      induced a stress response mediated by DNA damage-inducible transcript 3 to
      attenuate cytokine production via inhibition of NF-kappaB and NFAT activities.
      These results uncover the previously unknown mechanism by which T cells
      accelerate essential amino acid uptake upon activation and adapt to essential
      amino acid starvation. Our results also raise the possibility for application of
      an LAT1 inhibitor as a new drug for therapy of disease caused by exaggerated
      immune response. 

PMID- 24038087
TI  - CD4+ T cell expression of MyD88 is essential for normal resolution of Chlamydia
      muridarum genital tract infection.
AB  - Resolution of Chlamydia genital tract infection is delayed in the absence of
      MyD88. In these studies, we first used bone marrow chimeras to demonstrate a
      requirement for MyD88 expression by hematopoietic cells in the presence of a wild
      type epithelium. Using mixed bone marrow chimeras we then determined that MyD88
      expression was specifically required in the adaptive immune compartment.
      Furthermore, adoptive transfer experiments revealed that CD4(+) T cell expression
      of MyD88 was necessary for normal resolution of genital tract infection. This
      requirement was associated with a reduced ability of MyD88(-/-)CD4(+) T cells to
      accumulate in the draining lymph nodes and genital tract when exposed to the same
      inflammatory milieu as wild-type CD4(+) T cells. We also demonstrated that the
      impaired infection control we observed in the absence of MyD88 could not be
      recapitulated by deficiencies in TLR or IL-1R signaling. In vitro, we detected an
      increased frequency of apoptotic MyD88(-/-)CD4(+) T cells upon activation in the
      absence of exogenous ligands for receptors upstream of MyD88. These data reveal
      an intrinsic requirement for MyD88 in CD4(+) T cells during Chlamydia infection
      and indicate that the importance of MyD88 extends beyond innate immune responses
      by directly influencing adaptive immunity. 

PMID- 24038089
TI  - An alternative role of C1q in bacterial infections: facilitating Streptococcus
      pneumoniae adherence and invasion of host cells.
AB  - Streptococcus pneumoniae (pneumococcus) is a major human pathogen, which evolved
      numerous successful strategies to colonize the host. In this study, we report a
      novel mechanism of pneumococcal-host interaction, whereby pneumococci use a host
      complement protein C1q, primarily involved in the host-defense mechanism, for
      colonization and subsequent dissemination. Using cell-culture infection assays
      and confocal microscopy, we observed that pneumococcal surface-bound C1q
      significantly enhanced pneumococcal adherence to and invasion of host epithelial
      and endothelial cells. Flow cytometry demonstrated a direct, Ab-independent
      binding of purified C1q to various clinical isolates of pneumococci. This
      interaction was seemingly capsule serotype independent and mediated by the
      bacterial surface-exposed proteins, as pretreatment of pneumococci with pronase E
      but not sodium periodate significantly reduced C1q binding. Moreover, similar
      binding was observed using C1 complex as the source of C1q. Furthermore, our data
      show that C1q bound to the pneumococcal surface through the globular heads and
      with the host cell-surface receptor(s)/glycosaminoglycans via its N-terminal
      collagen-like stalk, as the presence of C1q N-terminal fragment and low m.w.
      heparin but not the C-terminal globular heads blocked C1q-mediated pneumococcal
      adherence to host cells. Taken together, we demonstrate for the first time, to
      our knowledge, a unique function of complement protein C1q, as a molecular bridge
      between pneumococci and the host, which promotes bacterial cellular adherence and
      invasion. Nevertheless, in some conditions, this mechanism could be also
      beneficial for the host as it may result in uptake and clearance of the bacteria.

PMID- 24038090
TI  - Regulation of the development of the hepatic B cell compartment during
      Schistosoma mansoni infection.
AB  - During infection with the helminth parasite Schistosoma mansoni, Ab regulates
      hepatic inflammation, and local production of Ig in the liver appears to play a
      role in this process. Exploring the development of the B cell response during
      infection, we found that parasite-specific IgG1-secreting plasma cells appeared
      first in the hepatic and mesenteric lymph nodes (LNs) and then at later times in
      the spleen, liver, and bone marrow. The LN B cell population peaked between weeks
      10 and 12 of infection, and then contracted at a time that coincided with the
      expansion of the hepatic IgG1(+) B cell compartment, suggesting that B cells
      migrate from LNs to liver. CXCL9 and -16 expression in the liver increased during
      the time frame of B cell recruitment. Expression of the CXCL16 receptor CXCR6 was
      increased on B cells within the hepatic LNs, but not the mesenteric LNs. CXCR3,
      the receptor for CXCL9, was broadly expressed on IgG1(+) B cells in LNs and liver
      during infection. Increased hepatic expression of CXCL9 and -16 failed to occur
      if the IL-10R was blocked in vivo, an intervention associated with decreased
      liver B cell infiltration and the development of severe disease. Hepatic LN
      IgG1(+) cells migrated toward CXCL9 and -16 in vitro and to the liver in a
      pertussis toxin-sensitive fashion. Our data suggest that the coordinated
      expression of CXCL9 and -16 in the liver and of CXCR6 and CXCR3 on responding B
      cells within the hepatic LNs underpins establishment of the hepatic B cell
      infiltrate during chronic schistosomiasis. 

PMID- 24038091
TI  - Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated
      fatty acids, exerts protective actions in murine models of colitis.
AB  - It has been previously reported that dietary fish oils, which are rich in the
      polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, can
      exert beneficial effects in inflammatory bowel disease. In this study, we
      investigated the effects of docosahexaenoic acid-derived lipid mediator maresin 1
      (MaR1) in dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid
      induced colitis in mice. Systemic treatment with MaR1 significantly attenuated
      both DSS- and 2,4,6-trinitrobenzene sulfonic acid-induced colonic inflammation by
      improving the disease activity index and reducing body weight loss and colonic
      tissue damage. MaR1 treatment also induced a significant decrease in levels of
      inflammatory mediators, such as IL-1beta, TNF-alpha, IL-6, and IFN-gamma, in the
      acute protocol, as well as IL-1beta and IL-6, but not TNF-alpha and INF-gamma, in
      the chronic DSS colitis protocol. Additionally, MaR1 decreased ICAM-1 mRNA
      expression in both the acute and chronic protocols of DSS-induced colitis.
      Furthermore, the beneficial effects of MaR1 seem to be associated with inhibition
      of the NF-kappaB pathway. Moreover, incubation of LPS-stimulated bone marrow
      derived macrophage cultures with MaR1 reduced neutrophil migration and reactive
      oxygen species production, besides decreasing IL-1beta, TNF-alpha, IL-6, and INF
      gamma production. Interestingly, macrophages incubated only with MaR1 showed a
      significant upregulation of mannose receptor C, type 1 mRNA expression, an M2
      macrophage phenotype marker. These results indicate that MaR1 consistently
      protects mice against different models of experimental colitis, possibly by
      inhibiting the NF-kappaB pathway and consequently multiple inflammatory
      mediators, as well as by enhancing the macrophage M2 phenotype.

PMID- 24038092
TI  - Interruption of dendritic cell-mediated TIM-4 signaling induces regulatory T
      cells and promotes skin allograft survival.
AB  - Dendritic cells (DCs) are the central architects of the immune response, inducing
      inflammatory or tolerogenic immunity, dependent on their activation status. As
      such, DCs are highly attractive therapeutic targets and may hold the potential to
      control detrimental immune responses. TIM-4, expressed on APCs, has complex
      functions in vivo, acting both as a costimulatory molecule and a
      phosphatidylserine receptor. The effect of TIM-4 costimulation on T cell
      activation remains unclear. In this study, we demonstrate that Ab blockade of DC
      expressed TIM-4 leads to increased induction of induced regulatory T cells
      (iTregs) from naive CD4(+) T cells, both in vitro and in vivo. iTreg induction
      occurs through suppression of IL-4/STAT6/Gata3-induced Th2 differentiation. In
      addition, blockade of TIM-4 on previously activated DCs still leads to increased
      iTreg induction. iTregs induced under TIM-4 blockade have equivalent potency to
      control and, upon adoptive transfer, significantly prolong skin allograft
      survival in vivo. In RAG(-/-) recipients of skin allografts adoptively
      transferred with CD4(+) T cells, we show that TIM-4 blockade in vivo is
      associated with a 3-fold prolongation in allograft survival. Furthermore, in this
      mouse model of skin transplantation, increased induction of allospecific iTregs
      and a reduction in T effector responses were observed, with decreased Th1 and Th2
      responses. This enhanced allograft survival and protolerogenic skewing of the
      alloresponse is critically dependent on conversion of naive CD4(+) to Tregs in
      vivo. Collectively, these studies identify blockade of DC-expressed TIM-4 as a
      novel strategy that holds the capacity to induce regulatory immunity in vivo. 

PMID- 24038093
TI  - TCF-1 controls ILC2 and NKp46+RORgammat+ innate lymphocyte differentiation and
      protection in intestinal inflammation.
AB  - Innate lymphocyte populations play a central role in conferring protective
      immunity at the mucosal frontier. In this study, we demonstrate that T cell
      factor 1 (TCF-1; encoded by Tcf7), a transcription factor also important for NK
      and T cell differentiation, is expressed by multiple innate lymphoid cell (ILC)
      subsets, including GATA3(+) nuocytes (ILC2) and NKp46(+) ILCs (ILC3), which
      confer protection against lung and intestinal inflammation. TCF-1 was
      intrinsically required for the differentiation of both ILC2 and NKp46(+) ILC3.
      Loss of TCF-1 expression impaired the capacity of these ILC subsets to produce IL
      5, IL-13, and IL-22 and resulted in crippled responses to intestinal infection
      with Citrobacter rodentium. Furthermore, a reduction in T-bet expression required
      for Notch-2-dependent development of NKp46(+) ILC3 showed a dose-dependent
      reduction in TCF-1 expression. Collectively, our findings demonstrate an
      essential requirement for TCF-1 in ILC2 differentiation and reveal a link among
      Tcf7, Notch, and Tbx21 in NKp46(+) ILC3 development. 

PMID- 24038094
TI  - Saccharomyces boulardii and Bacillus subtilis B10 modulate TLRs mediated
      signaling to induce immunity by chicken BMDCs.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play
      a critical role to activate immune response. They may be targeted for
      immunomodulation by microbes, including probiotics. In this study, chicken bone
      marrow dendrite cells (chi-BMDCs) were stimulated with lipopolysachride (LPS),
      Saccharomyces boulardii (Sb), Bacillus subtilis B10 (Bs), co-culture of Sb + Bs
      and phosphate buffer saline (PBS) as a control group (Ctr) at 3, 6, and 12 h
      intervals. Results revealed that treatment groups modulated the phenotype and
      biological functions of chi-BMDCs. Scan electron microscopy showed attachment of
      probiotics on the surface of chi-BMDCs. Additionally transmission electron
      microscopy (TEM) revealed efficiently engulfing and degradation of probiotics.
      Gene expression levels of MHC-II, CD40, CD80 and CD86 up-regulated in stimulated
      groups. Furthermore, toll-like receptors TLR1, TLR2, TLR4, and chicken specific
      TLR15 expressions were improved and downstream associated factors MyD88, TRAF6,
      TAB1, and NFkappa-B mRNA levels increased in all treatment groups as compared to
      control. Surprisingly, NFkappa-B response was noted significant higher in LPS
      treatment among all groups. Moreover, IL-1beta, IL-17, IL-4, TGF-beta, and IL-10
      production levels were found higher, and lower concentration of INF-gamma and IL
      8 were observed in Sb, Bs, and Sb + Bs treatment groups. In contrast, LPS groups
      showed prominent increase in IL-12, INF-gamma, and IL-8 concentration levels as
      compared to control group. Altogether, these results emphasize a potentially
      important role of Saccharomyces boulardii and Bacillus subtilis B10 in modulating
      immunological functions of chi-BMDCs by targeting specific toll like receptors
      (TLRs) and associated factors. The role of probiotics on chi-BMDCs functionality
      in a non-mammalian species have been presented for the first time.

PMID- 24038095
TI  - Understanding the impact of crop and food production on the water environment-
      using sugar as a model.
AB  - The availability of fresh water and the quality of aquatic ecosystems are
      important global concerns, and agriculture plays a major role. Consumers and
      manufacturers are increasingly sensitive to sustainability issues related to
      processed food products and drinks. The present study examines the production of
      sugar from the growing cycle through to processing to the factory gate, and
      identifies the potential impacts on water scarcity and quality and the ways in
      which the impact of water use can be minimised. We have reviewed the production
      phases and processing steps, and how calculations of water use can be
      complicated, or in some cases how assessments can be relatively straightforward.
      Finally, we outline several ways that growers and sugar processors are improving
      the efficiency of water use and reducing environmental impact, and where further
      advances can be made. This provides a template for the assessment of other crops.

PMID- 24038098
TI  - Genetic testing: when prediction generates stigmatization.
AB  - Using grounded theory methodology, this study examined the experiences of six
      BRCA1/2 gene mutation carriers (mean age = 38.5 years). Three types of
      stigmatization were identified: stigmatization by anticipation, stigmatization
      through rejection, and stigmatization by affiliation. Participants described
      potential impacts on their womanhood, felt threatened by others, and revealed
      fears that their children would inherit their stigmatization. These findings
      indicate the importance of psychological support in the follow-up of such
      patients. 

PMID- 24038099
TI  - Caseous calcification of the mitral annulus: a review.
AB  - Caseous calcification of the mitral annulus (CCMA) is a rare variant of mitral
      annular calcification (MAC). Since most cardiologists are unfamiliar with CCMA,
      it is commonly misdiagnosed as an abscess, tumor or infective vegetation on the
      mitral valve. In most cases, conservative management for this lesion is
      sufficient. In this review, we will discuss the various aspects of this condition
      and illustrate the gross and histologic pathology as well as various imaging
      modalities (Ultrasound, Computed tomography, Cardiac Magnetic resonance) to
      assess this unusual cardiac mass. 

PMID- 24038100
TI  - The pathophysiological relationship and clinical significance of left atrial
      function and left ventricular diastolic dysfunction in beta-thalassemia major.
AB  - Iron deposition in combination with inflammatory and immunogenetic factors is
      involved in the pathophysiology of cardiac dysfunction in beta-thalassemia major.
      We investigated the mechanical and endocrine function of the left atrium and
      ventricle to identify early signs of dysfunction. We studied 90 patients (mean
      age: 29 +/- 11 years) with beta-thalassemia and normal left ventricular function
      and 90 age and sex-matched healthy controls. Patients and controls underwent a
      thorough cardiac echocardiographic study and measurements of the b-type (NT
      proBNP) and atrial natriuretic peptides (proANP). Patients underwent 24-hr Holter
      recordings for arrhythmia monitoring. In the patient group, atria were affected
      early during the course of the disease, prior to diastolic and systolic left
      ventricular dysfunction. The E/E'ratio (E Doppler mitral fast inflow to the
      corresponding tissue Doppler E) continually increased with age (P < 0.05) and
      reached levels indicating left ventricular diastolic dysfunction (E/E' > 15) in
      the third decade whereas indexes of active and passive atrial function decreased
      gradually throughout life. In controls, the E/E' ratio continually increased with
      age but with later (fifth decade) appearance of diastolic dysfunction and a
      compensatory increase in atrial active function. Both natriuretic peptides were
      significantly increased in patients compared to controls (558 +/- 141 and 2,580
      +/- 1,830 fmol/mL for NT-proBNP and proANP versus 332 +/- 106 and 1,331 +/- 1,134
      fmol/mL, respectively). Atrial fibrillation was found in a subgroup of 23 (26%)
      patients, older in age with mild diastolic function and enlarged, depressed
      atria. In conclusion, atrial mechanical depression seems to be a very early sign
      of cardiac damage. It may become echocardiographically evident even before
      diastolic and systolic dysfunction and is associated to supraventricular
      arrhythmias.

PMID- 24038101
TI  - Assessment of heavy metal contamination and bioaccumulation in soybean plants
      from mining and smelting areas of southern Hunan Province, China.
AB  - Soybean is one of most important dicotyledonous food crops and is widely planted
      in Hunan Province, China. However, mining activity causes contamination of the
      soil in which soybean grows. To assess the impact of mining-induced soil
      contamination on soybean plants, a geoaccumulation index (I(geo)) was used to
      evaluate 20 soil samples from the mining and smelting areas of southern Hunan
      Province. The results indicated that Zn ranged from uncontaminated to a
      moderately contaminated level (I(geo)<1), Pb was at a strongly contaminated level
      (I(geo)>3), and Cd was at an extremely contaminated level (I(geo)>5) across the
      whole study area. All of the studied soybean plants were affected by heavy metal
      Pb and Cd contamination, and the mean concentrations in seeds were 13.9 mg/kg and
      2.95 mg/kg, respectively. The estimated bioconcentration factor and translocation
      factor showed that the soybean roots had a strong Cd bioconcentration capability
      and the stems had a strong translocation capability in terms of Pb, Cd, and Zn,
      with preferential transference of metals to the soybean leaves. The bioavailable
      fraction in the soil was characterized by the exchangeable fraction of heavy
      metals. In the present study, the bioavailable fractions of Pb, Cd, and Zn were
      significantly positively correlated with the concentration of these metals in
      soybean tissues (roots, stems, leaves, husks, and seeds).

PMID- 24038102
TI  - Genistein versus ICI 182, 780: an ally or enemy in metastatic progression of
      prostate cancer.
AB  - BACKGROUND: Androgen signalling through the androgen receptor (AR) plays a
      critical role in prostate cancer (PCa) initiation and progression. Estrogen in
      synergy with androgen is essential for cell growth of the normal and malignant
      prostate. However, the exact role that estrogen and the estrogen receptor play in
      prostate carcinogenesis remains unclear. We have previously demonstrated the
      metastasis-promoting effect of an estrogen receptor beta (ERbeta) agonist
      (genistein) in a patient-derived PCa xenograft model mimicking localized and
      metastatic disease. METHODS: To test the hypothesis that the tumor-promoting
      activity of genistein was due to its estrogenic properties, we treated the
      xenograft-bearing mice with genistein and an anti-estrogen compound (ICI 182,
      780) and compared the differential gene expression using microarrays. RESULTS:
      Using a second xenograft model which was derived from another patient, we showed
      that genistein promoted disease progression in vivo and ICI 182, 780 inhibited
      metastatic spread. The microarray analysis revealed that the metallothionein (MT)
      gene family was differentially expressed in tumors treated by these compounds.
      Using qRT-PCR, the differences in expression levels were validated in the
      metastatic and non-metastatic LTL313 PCa xenograft tumor lines, both of which
      were originally derived from the same PCa patient. CONCLUSIONS: Together our data
      provide evidence that genistein stimulates and ICI 182, 780 inhibits metastatic
      progression, suggesting that these effects may be mediated by ERbeta signalling.

PMID- 24038103
TI  - Does long-term survival in patients with pancreatic cancer really exist? Results
      from the CONKO-001 study.
AB  - BACKGROUND: Long-term survival (LTS) in patients (pts) with pancreatic cancer is
      still uncommon, little data is available to identify long-term survivors. The
      CONKO-001 study, which established gemcitabine after resection as adjuvant
      therapy, may provide data to answer this question. METHODS: CONKO-001 pts with an
      overall survival >=5 years were compared to those who survived <5 years. Central
      re-evaluation of primary histology was performed. Univariate analysis with the
      chi(2) -test identified qualifying factors. Logistic regression was used to
      investigate the influence of these covariates on LTS. RESULTS: Of the evaluable
      354 CONKO-001 pts, 54 (15%) with an overall survival >=5 years were identified.
      It was possible to obtain tumor specimens of 39 pts (72%). Histological re
      evaluation confirmed adenocarcinoma in 38 pts, 1 showed a high-grade
      neuroendocrine tumor. Univariate analysis for all 53 LTS pts with adenocarcinoma
      compared to the remaining 300 non-LTS pts revealed as relevant active treatment,
      tumor grading, tumor size, lymph nodes. No significance could be demonstrated for
      resection margin, sex, age, Karnofsky performance status, CA 19-9 at study entry.
      In multivariate analysis, tumor grading, active treatment, tumor size, lymph node
      involvement were independent prognostic factors for LTS. CONCLUSION: Long-term
      survival can be achieved in adenocarcinoma of the pancreas.

PMID- 24038104
TI  - High-resolution ultrasound visualization of the subcutaneous nerves of the
      forearm: a feasibility study in anatomic specimens.
AB  - INTRODUCTION: The aim of this ultrasound-anatomical study was to evaluate the
      ability of high-resolution ultrasound (HRUS) to visualize and infiltrate small
      subcutaneous nerves of the forearm in anatomic specimens. METHODS: Seven
      nonembalmed human bodies (4 men, 3 women; mean age at death, 60 years) were
      included in the study. Two investigators scanned the anatomic specimens using 15
      MHz and 18-MHz HRUS transducers. The lateral, medial, and posterior antebrachial
      cutaneous nerves were scanned and interventionally marked with ink using HRUS
      guidance. Subsequently, dissections were performed to assess the anatomical
      correlation of HRUS findings. RESULTS: All 3 nerves were identified consistently
      using HRUS. The precision of the ink-markings was excellent, with good
      correlation with the small peripheral branches of all 3 nerves. CONCLUSIONS: HRUS
      can identify precisely the small subcutaneous nerves of the forearm and may aid
      in both diagnosis and therapy in cases of neuropathy.

PMID- 24038105
TI  - Nonparametric estimation in an "illness-death" model when all transition times
      are interval censored.
AB  - We develop nonparametric maximum likelihood estimation for the parameters of an
      irreversible Markov chain on states {0,1,2} from the observations with interval
      censored times of 0 -> 1, 0 -> 2 and 1 -> 2 transitions. The distinguishing
      aspect of the data is that, in addition to all transition times being interval
      censored, the times of two events (0 -> 1 and 1 -> 2 transitions) can be censored
      into the same interval. This development was motivated by a common data structure
      in oral health research, here specifically illustrated by the data from a
      prospective cohort study on the longevity of dental veneers. Using the self
      consistency algorithm we obtain the maximum likelihood estimators of the
      cumulative incidences of the times to events 1 and 2 and of the intensity of the
      1 -> 2 transition. This work generalizes previous results on the estimation in an
      "illness-death" model from interval censored observations. 

PMID- 24038106
TI  - A transplantable TH-MYCN transgenic tumor model in C57Bl/6 mice for preclinical
      immunological studies in neuroblastoma.
AB  - Current multimodal treatments for patients with neuroblastoma (NBL), including
      anti-disialoganglioside (GD2) monoclonal antibody (mAb) based immunotherapy,
      result in a favorable outcome in around only half of the patients with advanced
      disease. To improve this, novel immunocombinational strategies need to be
      developed and tested in autologous preclinical NBL models. A genetically well
      explored autologous mouse model for NBL is the TH-MYCN model. However, the
      immunobiology of the TH-MYCN model remains largely unexplored. We developed a
      mouse model using a transplantable TH-MYCN cell line in syngeneic C57Bl/6 mice
      and characterized the immunobiology of this model. In this report, we show the
      relevance and opportunities of this model to study immunotherapy for human NBL.
      Similar to human NBL cells, syngeneic TH-MYCN-derived 9464D cells endogenously
      express the tumor antigen GD2 and low levels of MHC Class I. The presence of the
      adaptive immune system had little or no influence on tumor growth, showing the
      low immunogenicity of the NBL cells. In contrast, depletion of NK1.1+ cells
      resulted in enhanced tumor outgrowth in both wild-type and Rag1(-/-) mice,
      showing an important role for NK cells in the natural anti-NBL immune response.
      Analysis of the tumor infiltrating leukocytes ex vivo revealed the presence of
      both tumor associated myeloid cells and T regulatory cells, thus mimicking human
      NBL tumors. Finally, anti-GD2 mAb mediated NBL therapy resulted in ADCC in vitro
      and delayed tumor outgrowth in vivo. We conclude that the transplantable TH-MYCN
      model represents a relevant model for the development of novel
      immunocombinatorial approaches for NBL patients. 

PMID- 24038107
TI  - Assessment of capacity for Health Policy and Systems Research and Analysis in
      seven African universities: results from the CHEPSAA project.
AB  - The importance of health policy and systems research and analysis (HPSR+A) is
      widely recognized. Universities are central to strengthening and sustaining the
      HPSR+A capacity as they teach the next generation of decision-makers and health
      professionals. However, little is known about the capacity of universities,
      specifically, to develop the field. In this article, we report results of
      capacity self- assessments by seven universities within five African countries,
      conducted through the Consortium for Health Policy and Systems Analysis in Africa
      (CHEPSAA). The capacity assessments focused on both capacity 'assets' and
      'needs', and covered the wider context, as well as organizational and individual
      capacity levels. Six thematic areas of capacity were examined: leadership and
      governance, organizations' resources, scope of HPSR+A teaching and research,
      communication, networking and getting research into policy and practice (GRIPP),
      demand for HPRS+A and resource environment. The self-assessments by each
      university used combinations of document reviews, semi-structured interviews and
      staff surveys, followed by comparative analysis. A framework approach, guided by
      the six thematic areas, was used to analyse data. We found that HPSR+A is an
      international priority, and an existing activity in Africa, though still
      neglected field with challenges including its reliance on unpredictable
      international funding. All universities have capacity assets, such as ongoing
      HPSR+A teaching and research. There are, however, varying levels of assets (such
      as differences in staff numbers, group sizes and amount of HPSR+A teaching and
      research), which, combined with different capacity needs at all three levels
      (such as individual training, improvement in systems for quality assurance and
      fostering demand for HPSR+A work), can shape a future agenda for HPSR+A capacity
      strengthening. Capacity assets and needs at different levels appear related.
      Possible integrated strategies for strengthening universities' capacity include:
      refining HPSR+A vision, mainstreaming the subject into under- and post-graduate
      teaching, developing emerging leaders and aligning HPSR+A capacity strengthening
      within the wider organizational development. 

PMID- 24038108
TI  - The effects of a semi-rigid ankle brace on a simulated isolated subtalar joint
      instability.
AB  - Subtalar joint instability is hypothesized to occur after injuries to the
      calcaneofibular ligament (CFL) in isolation or in combination with the cervical
      and the talocalcaneal interosseous ligaments. A common treatment for hindfoot
      instability is the application of an ankle brace. However, the ability of an
      ankle brace to promote subtalar joint stability is not well established. We
      assessed the kinematics of the subtalar joint, ankle, and hindfoot in the
      presence of isolated subtalar instability, investigated the effect of bracing in
      a CFL deficient foot and with a total rupture of the intrinsic ligaments, and
      evaluated how maximum inversion range of motion is affected by the position of
      the ankle in the sagittal plane. Kinematics from nine cadaveric feet were
      collected with the foot placed in neutral, dorsiflexion, and plantar flexion.
      Motion was applied with and without a brace on an intact foot and after
      sequentially sectioning the CFL and the intrinsic ligaments. Isolated CFL
      sectioning increased ankle joint inversion, while sectioning the CFL and
      intrinsic ligaments affected subtalar joint stability. The brace limited
      inversion at the subtalar and ankle joints. Additionally, examining the foot in
      dorsiflexion reduced ankle and subtalar joint motion.

PMID- 24038109
TI  - New highlights for relaxin.

PMID- 24038110
TI  - Variable length testing using the ordinal regression model.
AB  - Health questionnaires are often built up from sets of questions that are totaled
      to obtain a sum score. An important consideration in designing questionnaires is
      to minimize respondent burden. An increasingly popular method for efficient
      measurement is computerized adaptive testing; unfortunately, many health
      questionnaires do not meet the requirements for this method. In this paper, a new
      sequential method for efficiently obtaining sum scores via the computer is
      introduced, which does not have such requirements and is based on the ordinal
      regression model. In the assessment, future scores are predicted from past
      responses, and when an acceptable level of uncertainty is achieved, the procedure
      is terminated. Two simulation studies were performed to illustrate the usefulness
      of the procedure. The first used artificially generated symptom scores, and the
      second was a post hoc simulation using real responses on the Center for
      Epidemiologic Studies Depression scale. In both studies, the sequential method
      substantially reduced the respondent burden while maintaining a high sum score
      quality. Benefits and limitations of this new methodology are discussed.

PMID- 24038111
TI  - Evaluation of sensorial, phytochemical and biological properties of new isotonic
      beverages enriched with lemon and berries during shelf life.
AB  - BACKGROUND: The aim of this work was to design new isotonic drinks with lemon
      juice and berries: maqui (Aristotelia chilensis (Molina) Stuntz), acai (Euterpe
      oleracea Mart.) and blackthorn (Prunus spinosa L.), following previous research.
      Quality parameters, sensorial attributes, antioxidant activities (ABTS(+),
      DPPH(*) and O2(*-) assays) and biological capacities (alpha-glucosidase and
      lipase inhibitory assays) were evaluated over 70 days of shelf-life period.
      RESULTS: Maqui isotonic blends were the most active in all antioxidant assays
      (8.35 and 3.07 mmol L(-1) Trolox for ABTS(+) and DPPH(*)), in the lipase
      inhibitory assay (43.19 U L(-1)), and showed the highest total phenol content by
      the Folin-Ciocalteu test (80.97 mg 100 mL(-1) gallic acid), as a result of its
      higher content of total anthocyanins (42.42 mg 100 mL(-1)). Berry mixtures were
      also the most potent inhibitors of alpha-glucosidase between all samples, and
      displayed an attractive red colour and good sensorial attributes. CONCLUSIONS:
      All the studied parameters remained quite stable during preservation, in general,
      and the new isotonic drinks can be useful to equilibrate redox balance in acute
      and intense exercise, and support weight loss programmes, avoiding triglyceride
      absorption and hyperglycaemia involved in obesity and diabetes mellitus,
      respectively. Further research in vivo is necessary to verify their beneficial
      effects for sports, nutrition and health.

PMID- 24038113
TI  - Sonography of trapezial ridge fractures.
AB  - Trapezial ridge fractures are very rare. These can be a diagnostic challenge and
      one needs to have a high index of suspicion. We report two cases of trapezial
      ridge fractures that were diagnosed sonographically and confirmed by cross
      sectional imaging (CT or MRI).

PMID- 24038112
TI  - Hepatocyte nuclear factors 4alpha and 1alpha regulate kidney developmental
      expression of drug-metabolizing enzymes and drug transporters.
AB  - The transcriptional regulation of drug-metabolizing enzymes and transporters
      (here collectively referred to as DMEs) in the developing proximal tubule (PT) is
      not well understood. As in the liver, DME regulation in the PT may be mediated
      through nuclear receptors, which are thought to "sense" deviations from
      homeostasis by being activated by ligands, some of which are handled by DMEs,
      including drug transporters. Systems analysis of transcriptomic data during
      kidney development predicted a set of upstream transcription factors, including
      hepatocyte nuclear factor 4alpha (Hnf4a) and Hnf1a, as well as Nr3c1 (Gr), Nfe2l2
      (Nrf2), peroxisome proliferator-activated receptor alpha (Pparalpha), and Tp53.
      Motif analysis of cis-regulatory enhancers further suggested that Hnf4a and Hnf1a
      are the main transcriptional regulators of DMEs in the PT. Available expression
      data from tissue-specific Hnf4a knockout tissues revealed that distinct subsets
      of DMEs were regulated by Hnf4a in a tissue-specific manner. Chromatin
      immunoprecipitation combined with massively parallel DNA sequencing was performed
      to characterize the PT-specific binding sites of Hnf4a in rat kidneys at three
      developmental stages (prenatal, immature, adult), which further supported a major
      role for Hnf4a in regulating PT gene expression, including DMEs. In ex vivo
      kidney organ culture, an antagonist of Hnf4a (but not a similar inactive
      compound) led to predicted changes in DME expression, including among others
      Fmo1, Cyp2d2, Cyp2d4, Nqo2, as well as organic cation transporters and organic
      anion transporters Slc22a1 (Oct1), Slc22a2 (Oct2), Slc22a6 (Oat1), Slc22a8
      (Oat3), and Slc47a1 (Mate1). Conversely, overexpression of Hnf1a and Hnf4a in
      primary mouse embryonic fibroblasts, sometimes considered a surrogate for
      mesenchymal stem cells, induced expression of several of these proximal tubule
      DMEs, as well as epithelial markers and a PT-enriched brush border marker Ggt1.
      These cells had organic anion transporter function. Taken together, the data
      strongly supports a critical role for HNF4a and Hnf1a in the tissue-specific
      regulation of drug handling and differentiation toward a PT-like cellular
      identity. We discuss our data in the context of the "remote sensing and signaling
      hypothesis" (Ahn and Nigam, 2009; Wu et al., 2011). 

PMID- 24038114
TI  - Determining factors predictive of CD34+ cell collection efficiency in an effort
      to avoid extended and repeated apheresis sessions.
AB  - INTRODUCTION: Collection efficiency (CE) is a reflection of the proportion of
      cells passing through a cell separator that is harvested. The aim of our study
      was to evaluate which factors influence CE independently in order to find ways to
      improve CE and therefore minimize the costs and risks of leukapheresis and graft
      processing. MATERIALS AND METHODS: A total of 206 consecutive apheresis
      procedures performed on 128 donors/patients were studied retrospectively. We
      explored the association between CE and the following factors: age, sex, weight,
      mobilization (granulocyte-colony-stimulating factor with or without
      chemotherapy), collection type (autologous versus allogeneic), venous access
      (peripheral versus central), total processed blood volume (TPV), hematocrit,
      white blood cell (WBC) count, thrombocyte count, and peripheral blood CD34+ cell
      concentration (PBCD34+). RESULTS: Stepwise multiple regression analysis showed
      WBC count to be the single best predictor of CE, accompanied by TPV. When
      performing subgroup analysis for autologous apheresis procedures, the inverse
      correlation of WBC count and TPV with CE becomes stronger (r = -0.563 with P <
      0.001 and r = -0.198 with P = 0.020 respectively), whereas those correlations
      disappear when analyzing only allogeneic apheresis procedures. CONCLUSION: The
      negative correlation between TPV and CE present only in autologous collection
      procedures can be explained by the limited intra-apheresis recruitment of CD34+
      cells into the blood which is negatively influenced by extensive pre-treatment.
      As a result of this study we decided to limit TPV to a maximum of three times the
      patient's blood volume in autologous apheresis procedures at our center.

PMID- 24038115
TI  - Gestures and social-emotional communicative development in chimpanzee infants.
AB  - Communicative skills of chimpanzees are of significant interest across many
      domains, such as developmental psychology (how does communication emerge in
      prelinguistic beings?), evolution (e.g., did human language evolve from primate
      gestures?), and in comparative psychology (how does the nonverbal communication
      of chimpanzees and humans compare?). Here we ask about how gestures develop in
      chimpanzee infants (n = 16) that were raised in an interactive program designed
      to study skill development. Data on socio-communicative development were
      collected following 4 hr of daily interaction with each infant, longitudinally
      from birth through the first year of life. A consistent and significant
      developmental pattern was found across the contexts of tickle play, grooming, and
      chase play: Infant chimpanzees first engaged in interactions initiated by others,
      then they initiated interactions, and finally, they requested others to join them
      in the interaction. Gestures were documented for initiating and requesting tickle
      play, for initiating and requesting grooming, and for initiating and requesting
      chase play. Gestural requests emerged significantly later than gestural
      initiations, but the age at which gestures emerged was significantly different
      across contexts. Those gestures related to hierarchical rank relations, that is,
      gestures used by subordinates in interaction with more dominant individuals, such
      as wrist presenting and rump presenting, did not emerge in the same manner as the
      other gestures. This study offers a new view on the development of gestures,
      specifically that many develop through interaction and communicate socio
      emotional desires, but that not all gestures emerge in the same manner.

PMID- 24038116
TI  - Indocyanine green retention test as a noninvasive marker of portal hypertension
      and esophageal varices in compensated liver cirrhosis.
AB  - Noninvasive markers would be useful for the assessment of portal hypertension
      (PH) and esophageal varices (EV) in patients with cirrhosis. The aim of our study
      was to evaluate the performance of the indocyanine green (ICG) retention test as
      a noninvasive marker of PH and EV, measured against the gold standards (hepatic
      venous pressure gradient [HVPG] measurement and upper endoscopy). We
      prospectively enrolled patients with compensated cirrhosis referral to our unit.
      All patients underwent laboratory tests, abdominal ultrasound, upper
      gastrointestinal endoscopy, HVPG measurement, and the ICG 15-minute retention
      (ICG-r15) test. We evaluated the sensitivity and specificity of the ICG retention
      test and other noninvasive tools for the diagnosis of PH and EV. Ninety-six
      consecutive Child-Pugh A patients (67 male and 29 female; 60.3 +/- 11.8 years of
      age) were enrolled. Seventy-four patients had clinically significant portal
      hypertension (CSPH), of whom 59 had severe portal hypertension (SPH). ICG-r15 and
      Lok index were independently related to the presence of both CSPH and SPH,
      whereas ICG-r15 and INR were related to EV. ICG-r15 values (<6.7% and <6.9%,
      respectively) were able to rule out the presence of CSPH and SPH (LR(-) 0.15 and
      0.14); ICG-r15 <10% provided a 97.8% sensitivity (LR(-) 0.042) for the exclusion
      of EV and a 100% sensitivity (LR(-) 0.0) for large EV. CONCLUSION: The ICG-r15
      test is an effective tool for assessment of PH in patients with compensated
      cirrhosis. Although this would not replace endoscopy, the ICG-r15 appears able to
      identify patients with advanced liver disease in which endoscopy is mandatory as
      well as rule out the presence of EV in patients with compensated cirrhosis.

PMID- 24038117
TI  - Undifferentiated sarcoma of the liver: a case study of an erythropoietin
      secreting tumor.
AB  - Undifferentiated embryonal sarcoma of the liver (UESL) is an uncommon hepatic
      tumor usually found in children, with rare cases reported in adults. We present a
      case of a 53-year-old woman with an undifferentiated sarcoma of the liver (USL),
      which resembles UESL, who initially presented with a markedly elevated hematocrit
      (61.2%). Cytogenetic studies for polycythemia vera were negative, but the
      patient's erythropoietin (EPO) was elevated. A computed tomography scan and
      subsequent partial hepatectomy revealed a well-circumscribed, partially cystic
      mass in the right lobe of the liver measuring 34 cm. Following surgery, the
      patient's EPO level and hematocrit dropped to within normal range and remained so
      for 1 year, at which point it rose again. A subsequent magnetic resonance imaging
      scan showed a liver mass at the previous resection margin, consistent with a
      recurrence. In this case study, we describe the first reported USL resembling an
      UESL that secretes EPO, which was a useful marker of tumor recurrence. 

PMID- 24038118
TI  - Overcoming dissipation in the calculation of standard binding free energies by
      ligand extraction.
AB  - This article addresses calculations of the standard free energy of binding from
      molecular simulations in which a bound ligand is extracted from its binding site
      by steered molecular dynamics (MD) simulations or equilibrium umbrella sampling
      (US). Host-guest systems are used as test beds to examine the requirements for
      obtaining the reversible work of ligand extraction. We find that, for both
      steered MD and US, marked irreversibilities can occur when the guest molecule
      crosses an energy barrier and suddenly jumps to a new position, causing
      dissipation of energy stored in the stretched molecule(s). For flexible
      molecules, this occurs even when a stiff pulling spring is used, and it is
      difficult to suppress in calculations where the spring is attached to the
      molecules by single, fixed attachment points. We, therefore, introduce and test a
      method, fluctuation-guided pulling, which adaptively adjusts the spring's
      attachment points based on the guest's atomic fluctuations relative to the host.
      This adaptive approach is found to substantially improve the reversibility of
      both steered MD and US calculations for the present systems. The results are then
      used to estimate standard binding free energies within a comprehensive framework,
      termed attach-pull-release, which recognizes that the standard free energy of
      binding must include not only the pulling work itself, but also the work of
      attaching and then releasing the spring, where the release work includes an
      accounting of the standard concentration to which the ligand is discharged.

PMID- 24038119
TI  - Estimating the adoption of transcatheter aortic valve replacement by US
      interventional cardiologists and clinical trialists.
AB  - BACKGROUND: Despite extensive attention dedicated to transcatheter aortic valve
      replacement (TAVR) in both the medical literature and lay press, little is known
      about the anticipated utilization of TAVR by the US cardiology community.
      HYPOTHESIS: TAVR use is likely to outstrip its initial clinical indications.
      METHODS: Four days after approval of the first TAVR device in November 2011 by
      the US Food and Drug Administration, we emailed an online questionnaire to 201
      authors of major TAVR clinical trials (trialists) and 461 recent members of an
      interventional cardiology professional society (clinicians). Responses were
      compared using chi(2) , t tests, and analysis of variance. RESULTS: Of 205
      surveys received (response rate 31%; 114 clinicians, 91 trialists), the majority
      of respondents were interventionalists (86%) working in academic practices (72%).
      Although most physicians anticipated referring <25% of their patients with severe
      aortic stenosis for TAVR, 68% believed that TAVR is equally efficacious as open
      heart surgery, and 11% believed that moderate-surgical risk patients should also
      be considered for TAVR. More clinicians (98%) than trialists (81%) expected to
      routinely refer patients for TAVR (P < 0.001). Furthermore, the clinicians were
      anticipating less operator training and lower annual volume requirements for
      performing TAVR, when compared with the trialists (P <= 0.001). CONCLUSIONS: Our
      findings suggest optimism for TAVR acceptance in the United States., with more
      conservative expectations regarding training, procedural volume requirements, and
      anticipated referral patterns among TAVR trialists than clinical
      interventionalists.

PMID- 24038120
TI  - Compound muscle action potential amplitude and distal potential duration in
      axonal neuropathy.

PMID- 24038121
TI  - Microcystins in potable surface waters: toxic effects and removal strategies.
AB  - In freshwater, harmful cyanobacterial blooms threaten to increase with global
      climate change and eutrophication of surface waters. In addition to the burden
      and necessity of removal of algal material during water treatment processes,
      bloom-forming cyanobacteria can produce a class of remarkably stable toxins,
      microcystins, difficult to remove from drinking water sources. A number of animal
      intoxications over the past 20 years have served as sentinels for widespread risk
      presented by microcystins. Cyanobacterial blooms have the potential to threaten
      severely both public health and the regional economy of affected communities,
      particularly those with limited infrastructure or resources. Our main objectives
      were to assess whether existing water treatment infrastructure provides
      sufficient protection against microcystin exposure, identify available options
      feasible to implement in resource-limited communities in bloom scenarios and to
      identify strategies for improved solutions. Finally, interventions at the
      watershed level aimed at bloom prevention and risk reduction for entry into
      potable water sources were outlined. We evaluated primary studies, reviews and
      reports for treatment options for microcystins in surface waters, potable water
      sources and treatment plants. Because of the difficulty of removal of
      microcystins, prevention is ideal; once in the public water supply, the coarse
      removal of cyanobacterial cells combined with secondary carbon filtration of
      dissolved toxins currently provides the greatest potential for protection of
      public health. Options for point of use filtration must be optimized to provide
      affordable and adequate protection for affected communities.

PMID- 24038122
TI  - Reversal of multidrug resistance in gastric cancer cells by E2F-1 downregulation
      in vitro and in vivo.
AB  - Transcription Factor E2F-1 plays a critical role in cell cycle regulation and
      other biological processes in cells. However whether or not it is involved in the
      multi-drug resistance (MDR) process of gastric cancer has not been fully
      elucidated yet. To explore the role of E2F-1 in the MDR process of gastric cancer
      in vitro and in vivo, a cisplatin-resistant gastric cancer cell line with stable
      downregulation of E2F-1 was established. E2F-1 shRNA led to downregulation of
      endogenous E2F-1 mRNA and protein. It significantly promoted the sensitivity of
      SGC7901/DDP cells to cisplatin, doxorubicin, and fluorouracil. Flow cytometry
      confirmed that the percentage of apoptotic cells increased after E2F-1
      downregulation. This notion was further supported by the observation that
      downregulation of E2F-1 blocked entry into the S-phase of the cell cycle.
      Furthermore, downregulation of E2F-1 significantly increased intracellular
      accumulation of doxorubicin. In addition, we determined the in vivo effects of
      E2F-1 small interfering RNA (shRNA) on tumor size, and apoptotic cells in tumor
      tissues were detected by deoxynucleotidyl transferase-mediated dUTP-biotin nick
      end labeling and hematoxylin and eosin staining. In molecular studies,
      semiquantitative RT-PCR and western blotting revealed that E2F-1 downregulation
      could inhibit expression of MDR1, MRP, Bcl-2/Bax, c-Myc, Skp2, Survivin, and
      Cyclin D1. IN CONCLUSION: E2F-1 may be involved in regulating multiple signaling
      pathways in reversing MDR, suggesting that E2F-1 may represent a novel target for
      gastric cancer therapy.

PMID- 24038123
TI  - Foot and ankle reconstruction: an experience on the use of 14 different flaps in
      226 cases.
AB  - The aim of this report was to present our experience on the use of different
      flaps for soft tissue reconstruction of the foot and ankle. From 2007 to 2012,
      the soft tissue defects of traumatic injuries of the foot and ankle were
      reconstructed using 14 different flaps in 226 cases (162 male and 64 female).
      There were 62 pedicled flaps and 164 free flaps used in reconstruction. The
      pedicled flaps included sural flap, saphenous flap, dorsal pedal neurocutaneous
      flap, pedicled peroneal artery perforator flap, pedicled tibial artery perforator
      flap, and medial plantar flap. The free flaps were latissimus musculocutaneous
      flap, anterolateral thigh musculocutaneous flap, groin flap, lateral arm flap,
      anterolateral thigh perforator flap, peroneal artery perforator flap,
      thoracdorsal artery perforator flap, medial arm perforator flap. The sensory
      nerve coaptation was not performed for all of flaps. One hundred and ninety-four
      cases were combined with open fractures. One hundred and sixty-two cases had
      tendon. Among 164 free flaps, 8 flaps were completely lost, in which the defects
      were managed by the secondary procedures. Among the 57 flaps for plantar foot
      coverage (25 pedicled flaps and 32 free flaps), ulcers were developed in 5
      pedicled flaps and 6 free flaps after weight bearing, and infection was found in
      14 flaps. The donor site complications were seen in 3 cases with the free
      anterolateral thigh perforator flap transfer. All of limbs were preserved and the
      patients regained walking and daily activities. All of patients except for one
      regained protective sensation from 3 to 12 months postoperatively. Our experience
      showed that the sural flap and saphenous flap could be good options for the
      coverage of the defects at malleolus, dorsal hindfoot and midfoot. Plantar foot,
      forefoot and large size defects could be reconstructed with free anterolateral
      thigh perforator flap. For the infected wounds with dead spce, the free
      latissimus dorsi musculocutaneous flap remained to be the optimal choice.

PMID- 24038125
TI  - Living in the time of sequestration.

PMID- 24038126
TI  - Should ethics standards for overseas trials get a makeover?: Transparency in
      overseas medical research has improved, but several issues concerning ethics of
      protections for trial participants remain unsolved.

PMID- 24038127
TI  - Recommendations from the presidential commission: The international research
      panel of the presidential commission for the study of bioethical issues released
      14 recommendations it says were needed to improve safety and reduce risk when
      conducting clinical trials nationally and internationally.

PMID- 24038128
TI  - Validation of a population of patient-specific adult acquired flatfoot deformity
      models.
AB  - Adult acquired flatfoot deformity (AAFD) is a degenerative disease resulting in
      malalignment of the mid- and hindfoot secondary to posterior tibial tendon
      dysfunction and increasing implication of ligament pathologies. Despite the
      complex 3D nature of AAFD, 2D radiographs are still employed to diagnose and
      stage the disease. Computer modeling techniques allow for accurate 3D recreations
      of musculoskeletal systems for the investigation of biomechanical factors
      contributing to disease. Following Institutional Review Board approval, the lower
      limbs of six diagnosed AAFD sufferers were imaged with MRI, photographs, and X
      ray. Next, a radiologist graded the MRI attenuation of eight soft-tissues
      implicated in AAFD. Six patient-specific rigid-body models were then created and
      loaded according to patient weight, graded soft-tissues, and extrinsic muscles.
      Model function was validated using clinically relevant kinematic measures in
      three planes. Agreement varied depending on the measure, with average absolute
      deviations of < 7 degrees  for angles and <4 mm for distances. Additionally, the
      clinically favored AP talonavicular coverage angle, ML talo-1st metatarsal angle,
      and ML 1st cuneiform height showed strong correlations of R(2) = 0.63, 0.75, and
      0.85, respectively. Thus, computer modeling offers a promising methodology for
      the non-invasive investigation of in vivo kinematic behavior in pathologic feet
      and, once validated, may further be used to investigate biomechanical parameters
      that are difficult to measure clinically.

PMID- 24038129
TI  - Atypical femoral fractures: transverse morphology at lateral cortex is a critical
      feature.
AB  - In 2010, the American Society for Bone and Mineral Research (ASBMR) task force
      defined major and minor features to assist in the case finding and reporting of
      atypical femoral fractures (AFFs). One major feature that was proposed was a
      "transverse or short oblique configuration." Our primary aim was to compare the
      conventional overall fracture morphology (OFM) with its associated angle (OFMA)
      and our proposed lateral cortical fracture angle (LCFA) in the assessment of
      fracture configuration in suspected AFFs and non-AFFs. The radiographs of 79
      patients with AFFs and 39 patients with non-AFFs were each analyzed by two
      blinded reviewers to obtain the OFM, OFMA, and LCFA. Using the overall fracture
      morphology to assess the suspected AFFs resulted in discordance between reviewers
      in 18 cases (22.8%), of which 5 (6.3%) were discordant between short oblique (>30
      degrees  to 60 degrees ) and long oblique (>60 degrees  to 90 degrees )
      configurations, therefore affecting their classifications as AFFs. By assessing
      only the critical component within the lateral cortex, all the suspected AFFs
      fell well within the classification as transverse fractures with a mean LCFA of
      4.8 degrees  (range 0.3 to 18.0, SD = 4.23). The inter-reader variability was
      also lower for LCFA versus OFMA (4.1 degrees  versus 6.9 degrees , p = 0.001)
      when used to assess AFFs. Fracture angles were significantly different in AFFs
      versus non-AFFs regardless of whether the OFMA or LCFA methodology was employed,
      but the greater difference associated with LCFA suggests its greater
      discriminating power. When LCFA was used in conjunction with 0 degrees  to 30
      degrees  as the criteria for transverse morphology, all the AFFs and non-AFFs
      were correctly classified. By using a standardized and precise method in
      measuring the fracture angle, specifically using only the component of the
      lateral cortex and limiting to truly transverse fractures, ie, between 0 degrees 
      and 30 degrees , the LCFA is a robust and accurate method to assess the fracture
      morphology in suspected AFFs.

PMID- 24038130
TI  - Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor
      controlled lipid homeostasis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is one of the major health concerns
      worldwide. Farnesoid X receptor (FXR) is considered a therapeutic target for
      treatment of NAFLD. However, the mechanism by which activation of FXR lowers
      hepatic triglyceride (TG) levels remains unknown. Here we investigated the role
      of hepatic carboxylesterase 1 (CES1) in regulating both normal and FXR-controlled
      lipid homeostasis. Overexpression of hepatic CES1 lowered hepatic TG and plasma
      glucose levels in both wild-type and diabetic mice. In contrast, knockdown of
      hepatic CES1 increased hepatic TG and plasma cholesterol levels. These effects
      likely resulted from the TG hydrolase activity of CES1, with subsequent changes
      in fatty acid oxidation and/or de novo lipogenesis. Activation of FXR induced
      hepatic CES1, and reduced the levels of hepatic and plasma TG as well as plasma
      cholesterol in a CES1-dependent manner. CONCLUSION: Hepatic CES1 plays a critical
      role in regulating both lipid and carbohydrate metabolism and FXR-controlled
      lipid homeostasis.

PMID- 24038132
TI  - Advances in the neuroimaging of panic disorder.
AB  - Models of the neuroanatomy of panic disorder (PD) have relied on both animal work
      on fear and on clinical data from neuroimaging. Early work hypothesised a network
      of brain regions involved in fear processing (e.g. the amygdala), but more recent
      work has also pointed to the involvement of other cortical areas and other brain
      circuitry (e.g. the insula and anterior cingulate cortex). Studies investigating
      functional and structural brain connectivity in PD may ultimately shed light on
      the extent to which the neuroanatomy of PD is localised versus distributed, and
      on how current treatments alter this neuroanatomy.

PMID- 24038131
TI  - Maturation of the developing human fetal prostate in a rodent xenograft model.
AB  - BACKGROUND: Prostate cancer is the most commonly diagnosed nonskin cancer in men.
      The etiology of prostate cancer is unknown, although both animal and
      epidemiologic data suggest that early life exposures to various toxicants, may
      impact DNA methylation status during development, playing an important role.
      METHODS: We have developed a xenograft model to characterize the growth and
      differentiation of human fetal prostate implants (gestational age 12-24 weeks)
      that can provide new data on the potential role of early life stressors on
      prostate cancer. The expression of key immunohistochemical markers responsible
      for prostate maturation was evaluated, including p63, cytokeratin 18, alpha
      smooth muscle actin, vimentin, caldesmon, Ki-67, prostate-specific antigen,
      estrogen receptor-alpha, and androgen receptor. Xenografts were separated into
      epithelial and stromal compartments using laser capture microdissection (LCM),
      and the DNA methylation status was assessed in >480,000 CpG sites throughout the
      genome. RESULTS: Xenografts demonstrated growth and maturation throughout the 200
      days of post-implantation evaluation. DNA methylation profiles of laser capture
      microdissected tissue demonstrated tissue-specific markers clustered by their
      location in either the epithelium or stroma of human prostate tissue.
      Differential methylated promoter region CpG-associated gene analysis revealed
      significantly more stromal than epithelial DNA methylation in the 30- and 90-day
      xenografts. Functional classification analysis identified CpG-related gene
      clusters in methylated epithelial and stromal human xenografts. CONCLUSION: This
      study of human fetal prostate tissue establishes a xenograft model that
      demonstrates dynamic growth and maturation, allowing for future mechanistic
      studies of the developmental origins of later life proliferative prostate
      disease.

PMID- 24038133
TI  - Stabilization of the integrase-DNA complex by Mg2+ ions and prediction of key
      residues for binding HIV-1 integrase inhibitors.
AB  - The HIV-1 integrase is an attractive target for the therapeutics development
      against AIDS, as no host homologue of this protein has been identified. The
      integrase strand transfer inhibitors (INSTIs), including raltegravir,
      specifically target the second catalytic step of the integration process by
      binding to the DDE motif of the catalytic site and coordinating Mg(2+) ions.
      Recent X-ray crystallographic structures of the integrase/DNA complex from
      prototype foamy virus allowed to investigate the role of the different partners
      (integrase, DNA, Mg(2+) ions, raltegravir) in the complex stability using
      molecular dynamics (MD) simulations. The presence of Mg(2+) ions is found to be
      essential for the stability, whereas the simultaneous presence of raltegravir and
      Mg(2+) ions has a destabilizing influence. A homology model of HIV-1 integrase
      was built on the basis of the X-ray crystallographic information, and protein
      marker residues for the ligand binding were detected by clustering the docking
      poses of known HIV-1 integrase inhibitors on the model. Interestingly, we had
      already identified some of these residues to be involved in HIV-1 resistance
      mutations and in the stabilization of the catalytic site during the MD
      simulations. Classification of protein conformations along MD simulations, as
      well as of ligand docking poses, was performed by using an original learning
      method, based on self-organizing maps. This allows us to perform a more in-depth
      investigation of the free-energy basins populated by the complex in MD
      simulations on the one hand, and a straightforward classification of ligands
      according to their binding residues on the other hand.

PMID- 24038134
TI  - The tangled web of Langer's lines.
AB  - Langer's lines are often considered to be guides for elective surgical incisions.
      Interestingly, Karl Langer was not the first to describe the property of skin
      that leads to the lines he depicted, nor are these lines in common use today.
      Rather, it is common that relaxed skin tension lines provide a guide for
      cosmetically pleasing surgical results. Nevertheless, Langer did conduct
      extensive studies on human skin that remain as a scholarly body of work.

PMID- 24038135
TI  - Bladder pain syndrome/interstitial cystitis is associated with anxiety disorder.
AB  - AIM: Recent research demonstrated that bladder pain syndrome/interstitial
      cystitis (BPS/IC) is associated with many coexisting physical and psychiatric
      conditions. In this study, we explored the potential association between anxiety
      disorder (AD) and BPS/IC using a case-controlled population-based approach in
      Taiwan. METHODS: Data on the sampled subjects analyzed in this study were
      retrieved from the Longitudinal Health Insurance Database 2000. Our study
      included 396 female cases with BPS/IC and 1,980 randomly selected female
      controls. We excluded subjects who had a history of major psychosis (except AD)
      or a substance-related disorder. A conditional logistic regression was performed
      to calculate the odds ratio (OR) for the association between a previous diagnosis
      of AD and IC/BPS. RESULTS: Of the 2,376 sampled subjects, 136 (5.72%) had
      received an AD diagnosis. AD was found in 64 (16.16%) cases and in 72 (3.64%)
      controls (P < 0.001). The conditional logistic regression analysis (conditioned
      on age group and the index year) suggested that compared to controls, the OR for
      prior AD among cases was 4.59 (95% confidence interval (CI) = 2.32-9.08, P <
      0.001). After adjusting for chronic pelvic pain, irritable bowel syndrome,
      fibromyalgia, migraines, sicca syndrome, allergies, asthma, and an overactive
      bladder, the OR for prior AD among cases was 4.37 (95% CI = 2.16-8.85, P < 0.001)
      compared to the controls. CONCLUSIONS: There was an association between AD and
      BPS/IC, even after taking demographic characteristics, medical co-morbidities,
      and substance-related disorders into consideration. Results of this study should
      alert clinicians to evaluate and monitor the presence of BPS/IC in patients with
      AD.

PMID- 24038136
TI  - Response to 'Improvement of arterial stiffness in the transition from acute
      decompensated heart failure to chronic compensated heart failure'.

PMID- 24038137
TI  - Recurrent patterning in the daily foraging routes of hamadryas baboons (Papio
      hamadryas): spatial memory in large-scale versus small-scale space.
AB  - The benefits of spatial memory for foraging animals can be assessed on two
      distinct spatial scales: small-scale space (travel within patches) and large
      scale space (travel between patches). While the patches themselves may be
      distributed at low density, within patches resources are likely densely
      distributed. We propose, therefore, that spatial memory for recalling the
      particular locations of previously visited feeding sites will be more
      advantageous during between-patch movement, where it may reduce the distances
      traveled by animals that possess this ability compared to those that must rely on
      random search. We address this hypothesis by employing descriptive statistics and
      spectral analyses to characterize the daily foraging routes of a band of wild
      hamadryas baboons in Filoha, Ethiopia. The baboons slept on two main cliffs--the
      Filoha cliff and the Wasaro cliff--and daily travel began and ended on a cliff;
      thus four daily travel routes exist: Filoha-Filoha, Filoha-Wasaro, Wasaro-Wasaro,
      Wasaro-Filoha. We use newly developed partial sum methods and distribution
      fitting analyses to distinguish periods of area-restricted search from more
      extensive movements. The results indicate a single peak in travel activity in the
      Filoha-Filoha and Wasaro-Filoha routes, three peaks of travel activity in the
      Filoha-Wasaro routes, and two peaks in the Wasaro-Wasaro routes; and are
      consistent with on-the-ground observations of foraging and ranging behavior of
      the baboons. In each of the four daily travel routes the "tipping points"
      identified by the partial sum analyses indicate transitions between travel in
      small- versus large-scale space. The correspondence between the quantitative
      analyses and the field observations suggest great utility for using these types
      of analyses to examine primate travel patterns and especially in distinguishing
      between movement in small versus large-scale space. Only the distribution-fitting
      analyses are inconsistent with the field observations, which may be due to the
      scale at which these analyses were conducted.

PMID- 24038138
TI  - Plasticity-related gene 1 is important for survival of neurons derived from rat
      neural stem cells.
AB  - Plasticity-related gene 1 (Prg1) is a membrane-associated lipid phosphate
      phosphatase. In this study, we first investigated the role of Prg1 in the
      survival of neurons derived from rat neural stem cells (NSCs) using small
      interfering RNA (siRNA). Prg1 knock-down decreased the cell number.
      Interestingly, Prg1 knock-down increased genomic DNA fragmentation, suggesting
      the possible induction of apoptosis. Exogenously expressed Prg1 rescued the cells
      from death and restored the loss of 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) activity induced with Prg1 siRNA. However,
      exogenously expressed mutated-Prg1 (the 253rd amino acid, histidine253, had been
      changed to alanine) did not rescue the cell death or restore the MTT activity.
      Histidine253 of Prg1 has been reported to be important for lipid phosphate
      phosphatase activity. These results suggest that Prg1 is important for survival
      of neurons through its dephosphorylation activity.

PMID- 24038139
TI  - Flexible nanodielectric materials with high permittivity for power energy
      storage.
AB  - Study of flexible nanodielectric materials (FNDMs) with high permittivity is one
      of the most active academic research areas in advanced functional materials.
      FNDMs with excellent dielectric properties are demonstrated to show great promise
      as energy-storage dielectric layers in high-performance capacitors. These
      materials, in common, consist of nanoscale particles dispersed into a flexible
      polymer matrix so that both the physical/chemical characteristics of the
      nanoparticles and the interaction between the nanoparticles and the polymers have
      crucial effects on the microstructures and final properties. This review first
      outlines the crucial issues in the nanodielectric field and then focuses on
      recent remarkable research developments in the fabrication of FNDMs with special
      constitutents, molecular structures, and microstructures. Possible reasons for
      several persistent issues are analyzed and the general strategies to realize
      FNDMs with excellent integral properties are summarized. The review further
      highlights some exciting examples of these FNDMs for power-energy-storage
      applications. 

PMID- 24038140
TI  - Porting ONETEP to graphical processing unit-based coprocessors. 1. FFT box
      operations.
AB  - We present the first graphical processing unit (GPU) coprocessor-enabled version
      of the Order-N Electronic Total Energy Package (ONETEP) code for linear-scaling
      first principles quantum mechanical calculations on materials. This work focuses
      on porting to the GPU the parts of the code that involve atom-localized fast
      Fourier transform (FFT) operations. These are among the most computationally
      intensive parts of the code and are used in core algorithms such as the
      calculation of the charge density, the local potential integrals, the kinetic
      energy integrals, and the nonorthogonal generalized Wannier function gradient. We
      have found that direct porting of the isolated FFT operations did not provide any
      benefit. Instead, it was necessary to tailor the port to each of the
      aforementioned algorithms to optimize data transfer to and from the GPU. A
      detailed discussion of the methods used and tests of the resulting performance
      are presented, which show that individual steps in the relevant algorithms are
      accelerated by a significant amount. However, the transfer of data between the
      GPU and host machine is a significant bottleneck in the reported version of the
      code. In addition, an initial investigation into a dynamic precision scheme for
      the ONETEP energy calculation has been performed to take advantage of the
      enhanced single precision capabilities of GPUs. The methods used here result in
      no disruption to the existing code base. Furthermore, as the developments
      reported here concern the core algorithms, they will benefit the full range of
      ONETEP functionality. Our use of a directive-based programming model ensures
      portability to other forms of coprocessors and will allow this work to form the
      basis of future developments to the code designed to support emerging high
      performance computing platforms.

PMID- 24038142
TI  - Role of TWEAK in coregulating liver progenitor cell and fibrogenic responses.

PMID- 24038141
TI  - Increased osteopontin contributes to inhibition of bone mineralization in FGF23
      deficient mice.
AB  - Excessive FGF23 has been identified as a pivotal phosphaturic factor leading to
      renal phosphate-wasting and the subsequent development of rickets and
      osteomalacia. In contrast, loss of FGF23 in mice (Fgf23(-/-) ) leads to high
      serum phosphate, calcium, and 1,25-vitamin D levels, resulting in early lethality
      attributable to severe ectopic soft-tissue calcifications and organ failure.
      Paradoxically, Fgf23(-/-) mice exhibit a severe defect in skeletal mineralization
      despite high levels of systemic mineral ions and abundant ectopic mineralization,
      an abnormality that remains largely unexplained. Through use of in situ
      hybridization, immunohistochemistry, and immunogold labeling coupled with
      electron microscopy of bone samples, we discovered that expression and
      accumulation of osteopontin (Opn/OPN) was markedly increased in Fgf23(-/-) mice.
      These results were confirmed by qPCR analyses of Fgf23(-/-) bones and ELISA
      measurements of serum OPN. To investigate whether elevated OPN levels were
      contributing to the bone mineralization defect in Fgf23(-/-) mice, we generated
      Fgf23(-/-) /Opn(-/-) double-knockout mice (DKO). Biochemical analyses showed that
      the hypercalcemia and hyperphosphatemia observed in Fgf23(-/-) mice remained
      unchanged in DKO mice; however, micro-computed tomography (uCT) and
      histomorphometric analyses showed a significant improvement in total mineralized
      bone volume. The severe osteoidosis was markedly reduced and a normal mineral
      apposition rate was present in DKO mice, indicating that increased OPN levels in
      Fgf23(-/-) mice are at least in part responsible for the osteomalacia. Moreover,
      the increased OPN levels were significantly decreased upon lowering serum
      phosphate by feeding a low-phosphate diet or after deletion of NaPi2a, indicating
      that phosphate levels contribute in part to the high OPN levels in Fgf23(-/-)
      mice. In summary, our results suggest that increased OPN is an important
      pathogenic factor mediating the mineralization defect and the alterations in bone
      metabolism observed in Fgf23(-/-) bones.

PMID- 24038143
TI  - The E2F1/DNMT1 axis is associated with the development of AR negative castration
      resistant prostate cancer.
AB  - BACKGROUND: Research on castration resistant prostate cancer (CRPC) has focused
      primarily on functional alterations of the androgen receptor (AR). However,
      little is known about the loss of AR gene expression itself and the possible
      contribution of AR negative cells to CRPC. METHODS: Human and murine prostate
      cancer tissue microarrays (TMAs) were evaluated with antibodies specific for
      E2F1, DNA methyltransferase 1 or AR. The human prostate cancer TMA consisted of
      clinical samples ranging from normal tissue to samples of metastatic disease. The
      murine TMA was comprised of benign, localized or metastatic prostate cancer
      acquired from TRAMP mice treated with castration and/or 5'-Aza-2'-deoxycytidine
      (5Aza). RESULTS: Immunohistochemical analysis revealed increased nuclear DNMT1
      staining in localized PCa (P < 0.0001) and metastatic PCa (P < 0.0001) compared
      to normal tissue. Examination of specific diagnoses revealed that Gleason seven
      tumors exhibited greater nuclear DNMT1 staining than Gleason six tumors (P <
      0.05) and that metastatic tissue exhibited greater levels of nuclear DNMT1 than
      Gleason seven tumors (P < 0.01). Evaluation of the murine tissue cores revealed
      that 8.2% and 8.1% of benign tissue cores stained positive for E2F1 and DNMT1
      respectively, while 97.0% were AR positive. Conversely, 81% and 100% of tumors
      were positive for E2F1 and DNMT1 respectively. This was in stark contrast to only
      18% of tumors positive for AR. Treatment of mice with 5Aza reduced DNMT1 staining
      by 30%, while AR increased by 27%. CONCLUSIONS: These findings demonstrate that
      the E2F1/DNMT1 inhibitory axis of AR transcription is activated during the
      emergence of CRPC.

PMID- 24038144
TI  - Ca2+ /calmodulin-dependent protein kinase II in spinal dorsal horn contributes to
      the pain hypersensitivity induced by gamma-aminobutyric acid type a receptor
      inhibition.
AB  - The fast inhibitory synaptic transmission mediated by the gamma-aminobutyric acid
      type A receptor (GABAA R) within spinal dorsal horn exerts a gating control over
      the synaptic conveyance of nociceptive information from the periphery to higher
      brain regions. Although a large body of evidence has demonstrated that the
      impairment of GABAergic inhibition alone is sufficient to elicit pain
      hypersensitivity in intact animals, the underlying mechanisms remain to be
      characterized. The present study shows that Ca(2+) /calmodulin-dependent protein
      kinase II (CaMKII) is an important signaling protein downstream of reduced
      GABAergic inhibition. We found that pharmacological removal of inhibition by
      intrathecal application of the GABAA R antagonist bicuculline significantly
      enhanced the autophosphorylation of CaMKII at Thr286 in spinal dorsal horn of
      mice. In addition to increased CaMKII activity, bicuculline also promoted CaMKII
      interaction with N-methyl-D-aspartate (NMDA)-subtype glutamate receptors and
      induced the translocation of CaMKII from cytosolic compartments to the
      synaptosomal membrane fraction. Immunoblotting analysis revealed that the
      phosphorylation levels of NMDA receptor NR2B subunit at Ser1303 and of AMPA
      subtype glutamate receptor GluR1 subunit at Ser831, two important CaMKII
      phosphorylation sites, were substantially enhanced after bicuculline application.
      Behavioral tests illustrated that intrathecal administration of the CaMKII
      inhibitor KN-93, NMDA receptor antagonist D-APV, or AMPA receptor antagonist GYKI
      52466 effectively ameliorated the mechanical allodynia evoked by bicuculline.
      These data thus indicate that CaMKII signaling is critical for the reduced
      inhibition to evoke spinal sensitization.

PMID- 24038146
TI  - PLCgamma2 and PKC are important to myeloid lineage commitment triggered by M-SCF
      and G-CSF.
AB  - Myeloid differentiation is a complex process whereby mature granulocytes or
      monocytes/macrophages are derived from a common myeloid progenitor through the
      coordinated action of hematopoietic cytokines. In this study, we explored the
      role of the Ca(2+)i signaling transduction pathway in the commitment of
      hematopoietic stem/progenitor cells to either the monocytic or granulocytic
      lineage in response to macrophage colony-stimulating factor (M-CSF) and
      granulocyte colony-stimulating factor (G-CSF). M-CSF and G-CSF induce cell
      expansion and monocyte or granulocyte differentiation, respectively, without
      affecting the percentage of hematopoietic progenitor cells. Colony-forming units
      (CFUs) and flow cytometry demonstrated the involvement of phospholipase Cgamma
      (PLCgamma) and protein kinase C (PKC) in monocyte/granulocyte commitment. In
      addition, using flow cytometry and RNA interference, we identified PLCgamma2 as
      the PLCgamma isoform that participates in this cell expansion and
      differentiation. Differences in signaling elicited by M-CSF and G-CSF were
      observed. The M-CSF-related effects were associated with the activation of ERK1/2
      and nuclear factor of activated T-cells (NFAT); the inhibition of both molecules
      reduced the number of colonies in a CFU assay. In contrast, using flow cytometry
      and confocal evaluation, we demonstrated that G-CSF activated Jak-1 and STAT-3.
      Additionally, the effects induced by G-CSF were also related with the
      participation of Ca(2+) calmodulin kinase II and the transcription factor PU.1.
      STAT-3 activation and the increase of PU.1 expression were sensitive to PLC
      inhibition by U73122. These data show that PLCgamma2 and PKC are important
      upstream signals that regulate myelopoiesis through cytokines, and differences in
      M-CSF and G-CSF downstream signaling were identified.

PMID- 24038145
TI  - Effects of butyltins on mitogen-activated-protein kinase kinase kinase and Ras
      activity in human natural killer cells.
AB  - Butyltins (BTs) contaminate the environment and are found in human blood. BTs,
      tributyltin (TBT) and dibutyltin (DBT) diminish the cytotoxic function and levels
      of key proteins of human natural killer (NK) cells. NK cells are an initial
      immune defense against tumors, virally infected cells and antibody-coated cells
      and thus critical to human health. The signaling pathways that regulate NK cell
      functions include mitogen-activated protein kinases (MAPKs). Studies have shown
      that exposure to BTs leads to activation of specific MAPKs and MAPK kinases
      (MAP2Ks) in human NK cells. MAP2K kinases (MAP3Ks) are upstream activators of
      MAP2Ks, which then activate MAPKs. The current study examined if BT-induced
      activation of MAP3Ks was responsible for MAP2K and thus, MAPK activation. This
      study examines the effects of TBT and DBT on the total levels of two MAP3Ks, c
      Raf and ASK1, as well as activating and inhibitory phosphorylation sites on these
      MAP3Ks. In addition, the immediate upstream activator of c-Raf, Ras, was examined
      for BT-induced alterations. Our results show significant activation of the MAP3K,
      c-Raf, in human NK cells within 10 min of TBT exposure and the MAP3K, ASK1, after
      1 h exposures to TBT. In addition, our results suggest that both TBT and DBT
      affect the regulation of c-Raf.

PMID- 24038147
TI  - How to select the most relevant 3D roughness parameters of a surface.
AB  - In order to conduct a comprehensive roughness analysis, around sixty 3D roughness
      parameters are created to describe most of the surface morphology with regard to
      specific functions, properties or applications. In this paper, a multiscale
      surface topography decomposition method is proposed with application to stainless
      steel (AISI 304), which is processed by rolling at different fabrication stages
      and by electrical discharge tool machining. Fifty-six 3D-roughness parameters
      defined in ISO, EUR, and ASME standards are calculated for the measured surfaces.
      Then, expert software "MesRug" is employed to perform statistical analysis on
      acquired data in order to find the most relevant parameters characterizing the
      effect of both processes (rolling and machining), and to determine the most
      appropriate scale of analysis. For the rolling process: The parameter Vmc (the
      Core Material Volume--defined as volume of material comprising the texture
      between heights corresponding to the material ratio values of p = 10% and q =
      80%) computed at the scale of 3 um is the most relevant parameter to characterize
      the cold rolling process. For the EDM Process, the best roughness parameter is
      SPD that represents the number of peaks per unit area after segmentation of a
      surface into motifs computed at the scale of 8 um.

PMID- 24038148
TI  - Prostatic alpha1-adrenoceptors: new concepts of function, regulation, and
      intracellular signaling.
AB  - Prostatic alpha1 -adrenoceptors are known to be involved in the pathophysiology
      of lower urinary tract symptoms (LUTS) in patients with benign prostate
      obstruction (BPO). It is widely accepted that enhanced alpha1 -adrenergic smooth
      muscle contraction can contribute to bladder outlet obstruction; alpha1 
      adrenoceptor antagonists still represent a gold standard in the treatment of
      LUTS. Accordingly, expression and function of alpha1 -adrenoceptors in the
      prostate have attracted large attention over the last three decades. However,
      recent preclinical studies have challenged our understanding of prostatic alpha1 
      adrenoceptors. In the current review article, we summarize "modern" concepts of
      prostatic alpha1 -adrenoceptors which include novel intracellular mediators of
      contraction as well as non-contractile signaling and post-translational receptor
      regulation. Configuration of alpha1 -adrenoceptors with binding partners may
      determine its function, leading to a dynamic receptor with high functional
      plasticity. Cooperative regulation of different intracellular effectors (MAPK,
      Akt, transcription factors) by alpha1 -adrenoceptors, hormones or growth factors
      has been suggested. The prostatic alpha1 -adrenoceptor is no longer being
      regarded as an isolated, static receptor exclusively mediating prostatic smooth
      muscle contraction by G proteins, but a dynamic receptor interacting with other
      receptors within a complex network of mediators.

PMID- 24038149
TI  - Giovanni Domenico Santorini (1681-1737): a prominent physician and meticulous
      anatomist.
AB  - Venetian physician Giovanni Domenico Santorini is revered as one of the most
      industrious and thorough anatomists of the eighteenth century. After receiving
      his medical degree in Pisa, Santorini worked as a physician and professor of
      anatomy and obstetrics in Venice. Of interest, he was a student of Malpighi while
      in Pisa. He quickly established himself as a dynamic lecturer and meticulous
      dissector. Santorini's anatomical observations include the prostatic venous
      plexus, accessory pancreatic duct, corniculate cartilage, parietal emissary
      veins, the risorius muscle, and many other structures. In addition to the
      detailed descriptions of these structures, he also produced copper plates and
      illustrations that are revered as "masterpieces" of that era. Santorini published
      Observationes anatomicae (Anatomical observations) in 1724, however his primary
      work, which included the description and anatomical drawings of the accessory
      pancreatic duct, was not published until thirty-eight years after his death. This
      posthumous release of Jo. Dominici Santorini anatomici summi septedecim tabulae
      [Giovanni Domenici Santorini, the excellent anatomist's seventeen drawings] was
      accomplished by Giambattista Morgagni and his disciple, Michael Girardi in 1775.
      Giovanni Santorini's assiduous dissections have significantly enhanced our
      knowledge of human anatomy and his work has been immortalized with several
      anatomical eponyms.

PMID- 24038150
TI  - Evaluation of knee joint muscle forces and tissue stresses-strains during gait in
      severe OA versus normal subjects.
AB  - Osteoarthritis (OA) is the leading cause of pain and disability in the elderly
      with the knee being the most affected weight bearing joint. We used a
      musculoskeletal biomechanical model of the lower extremity including a detailed
      validated knee joint finite element model to compute lower extremity muscle
      forces and knee joint stresses-strains during the stance phase of gait. The model
      was driven by gait data on OA patients, and results were compared with those of
      the same model driven by data on normal controls. Additional analyses were
      performed with altered cartilage-menisci properties to evaluate the effects of
      deterioration during OA. In OA patients compared to normal subjects, muscle
      forces dropped at nearly all stance periods except mid-stance. Force in the
      anterior cruciate ligament remained overall the same. Total contact forces
      stresses deceased by about 25%. Alterations in properties due to OA had
      negligible effects on muscle forces, but increased contact areas and cartilage
      strains and reduced contact pressures. Reductions in contact stresses and
      increases in tissue strains and transfer of load via menisci are partly due to
      the altered kinetics-kinematics of gait and partly due to deterioration in
      cartilage-menisci properties in OA patients.

PMID- 24038151
TI  - Critical interaction between E1 and E2 glycoproteins determines binding and
      fusion properties of hepatitis C virus during cell entry.
AB  - Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are important mediators
      for productive cell entry. However, knowledge about their structure, intra- or
      intermolecular dialogs, and conformational changes is scarce, limiting the design
      of therapeutic strategies targeting E1E2. Here we sought to investigate how
      certain domains of E1 and E2 have coevolved to optimize their interactions to
      promote efficient HCV entry. For this purpose we generated chimeric E1E2
      heterodimers derived from two HCV 1a strains to identify and characterize
      crosstalk between their domains. We found an E1E2 combination that drastically
      impaired the infectivity of cell culture-derived HCV particles, whereas the
      reciprocal E1E2 combination led to increased infectivity. Using HCV
      pseudoparticle assays, we confirmed the opposing entry phenotypes of these
      heterodimers. By mutagenesis analysis, we identified a particular crosstalk
      between three amino acids of E1 and the domain III of E2. Its modulation leads to
      either a full restoration of the functionality of the suboptimal heterodimer or a
      destabilization of the functional heterodimer. Interestingly, we found that this
      crosstalk modulates E1E2 binding to HCV entry receptors SR-BI and CD81. In
      addition, we found for the first time that E1E2 complexes can interact with the
      first extracellular loop of Claudin-1, whereas soluble E2 did not. These results
      highlight the critical role of E1 in the modulation of HCV binding to receptors.
      Finally, we demonstrated that this crosstalk is involved in membrane fusion.
      CONCLUSIONS: These results reveal a multifunctional and crucial interaction
      between E1 and E2 for HCV entry into cells. Our study highlights the role of E1
      as a modulator of HCV binding to receptors and membrane fusion, underlining its
      potential as an antiviral target.

PMID- 24038152
TI  - The effect of the cathepsin K inhibitor ONO-5334 on trabecular and cortical bone
      in postmenopausal osteoporosis: the OCEAN study.
AB  - ONO-5334 (Ono Pharmaceutical Co., Ltd., Osaka, Japan) inhibits cathepsin K and
      has been shown to increase areal bone mineral density (BMD) at the hip and spine
      in postmenopausal osteoporosis. Quantitative computed tomography (QCT) allows the
      study of the cortical and trabecular bone separately and provides structural
      information such as cortical thickness. We investigated the impact of 2 years of
      cathepsin K inhibition on these different bone compartments with ONO-5334. The
      clinical study was a randomized, double-blind, placebo, and active controlled
      parallel group study conducted in 13 centers in six European countries. The
      original study period of 12 months was extended by another 12 months. A total of
      147 subjects (age 55-75 years) of the QCT substudy who participated in the
      extension period were included. Subjects had been randomized into one of five
      treatment arms: placebo; ONO-5334 50 mg twice per day (BID); ONO-5334 100 mg once
      daily (QD); ONO-5334 300 mg QD; or alendronate 70 mg once weekly (QW). QCT was
      obtained to evaluate bone structure at the lumbar spine and proximal femur. After
      24 months ONO-5334 showed statistically significant increases versus placebo for
      integral, trabecular, and cortical BMD at the spine and the hip (for ONO-5334 300
      mg QD, BMD increases were 10.5%, 7.1%, and 13.4% for integral, cortical, and
      trabecular BMD at the spine, respectively, and 6.2%, 3.4%, and 14.6% for
      integral, cortical, and trabecular total femur BMD, respectively). Changes in
      cortical and trabecular BMD in the spine and hip were similar for alendronate as
      for ONO-5334. Integral volume did not demonstrate statistically significant
      changes under ONO-5334 treatment, thus there was no evidence of periosteal
      apposition, neither at the spine nor at the femur. Cortical thickness changes
      were not statistically significant for ONO-5334 in the spine and hip, with
      exception of a 2.1% increase after month 24 in the intertrochanter for ONO-5334
      300 mg QD. Over 2 years ONO-5334 showed a statistically significant and
      persistent increase of trabecular and integral BMD at the spine and the hip.
      Cortical BMD also progressively increased but at a lower rate. Changes in bone
      size and of periosteal apposition were not observed.

PMID- 24038153
TI  - Cell-material interactions revealed via material techniques of surface
      patterning.
AB  - Cell-material interactions constitute a key fundamental topic in biomaterials
      study. Various cell cues and matrix cues as well as soluble factors regulate cell
      behaviors on materials. These factors are coupled with each other as usual, and
      thus it is very difficult to unambiguously elucidate the role of each regulator.
      The recently developed material techniques of surface patterning afford unique
      ways to reveal the underlying science. This paper reviews the pertinent material
      techniques to fabricate patterns of microscale and nanoscale resolutions, and
      corresponding cell studies. Some issues are emphasized, such as cell localization
      on patterned surfaces of chemical contrast, and effects of cell shape, cell size,
      cell-cell contact, and seeding density on differentiation of stem cells. Material
      cues to regulate cell adhesion, cell differentiation and other cell events are
      further summed up. Effects of some physical properties, such as surface
      topography and matrix stiffness, on cell behaviors are also discussed; nanoscaled
      features of substrate surfaces to regulate cell fate are summarized as well. The
      pertinent work sheds new insight into the cell-material interactions, and is
      stimulating for biomaterial design in regenerative medicine, tissue engineering,
      and high-throughput detection, diagnosis, and drug screening. 

PMID- 24038154
TI  - CD8 T cells primed in the gut-associated lymphoid tissue induce immune-mediated
      cholangitis in mice.
AB  - The pathogenesis of primary sclerosing cholangitis (PSC) remains poorly
      understood. Since PSC predominantly occurs in patients with inflammatory bowel
      disease, autoimmunity triggered by activated T cells migrating from the gut to
      the liver is a possible mechanism. We hypothesized that T cells primed in the gut
      associated lymphoid tissue (GALT) by a specific antigen migrate to the liver and
      cause cholangitis when they recognize the same antigen on cholangiocytes. We
      induced ovalbumin-dependent colitis in mice that express ovalbumin in biliary
      epithelia (ASBT-OVA mice) and crossed ASBT-OVA mice with mice that express
      ovalbumin in enterocytes (iFABP-OVA mice). We analyzed T-cell activation in the
      GALT and crossreactivity to the same antigen in the liver as well as the effects
      of colitis per se on antigen-presentation and T-cell activation in the liver.
      Intrarectal application of ovalbumin followed by transfer of CD8 OT-I T cells led
      to antigen-dependent colitis. CD8 T cells primed in the GALT acquired effector
      function and the capability to migrate to the liver, where they caused
      cholangitis in a strictly antigen-dependent manner. Likewise, cholangitis
      developed in mice expressing ovalbumin simultaneously in biliary epithelia and
      enterocytes after transfer of OT-I T cells. Dextran sodium sulfate colitis led to
      increased levels of inflammatory cytokines in the portal venous blood, induced
      activation of resident liver dendritic cells, and promoted the induction of T
      cell-dependent cholangitis. CONCLUSION: Our data strengthen the notion that
      immune-mediated cholangitis is caused by T cells primed in the GALT and provide
      the first link between colitis and cholangitis in an antigen-dependent mouse
      model.

PMID- 24038155
TI  - Estimating the loss in expectation of life due to cancer using flexible
      parametric survival models.
AB  - A useful summary measure for survival data is the expectation of life, which is
      calculated by obtaining the area under a survival curve. The loss in expectation
      of life due to a certain type of cancer is the difference between the expectation
      of life in the general population and the expectation of life among the cancer
      patients. This measure is used little in practice as its estimation generally
      requires extrapolation of both the expected and observed survival. A parametric
      distribution can be used for extrapolation of the observed survival, but it is
      difficult to find a distribution that captures the underlying shape of the
      survival function after the end of follow-up. In this paper, we base our
      extrapolation on relative survival, because it is more stable and reliable.
      Relative survival is defined as the observed survival divided by the expected
      survival, and the mortality analogue is excess mortality. Approaches have been
      suggested for extrapolation of relative survival within life-table data, by
      assuming that the excess mortality has reached zero (statistical cure) or has
      stabilized to a constant. We propose the use of flexible parametric survival
      models for relative survival, which enables estimating the loss in expectation of
      life on individual level data by making these assumptions or by extrapolating the
      estimated linear trend at the end of follow-up. We have evaluated the
      extrapolation from this model using data on four types of cancer, and the results
      agree well with observed data.

PMID- 24038156
TI  - In vivo and in vitro evaluation of the effect of 2-(4-morpholinethyl)1
      phenylcyclohexanecarboxylate on inflammation-sensitized hyperoxia-induced
      developing brain injury.
AB  - Supraphysiological oxygen concentrations are toxic to the developing brain.
      Inflammatory processes increase the risk for brain injury. Sigma-1 receptor
      agonists are potent suppressors of inflammation-related events and are powerful
      immunomodulatory and antioxidative agents. Neuroprotective effects of sigma-1
      receptor agonists have been described previously for neonatal and adult models of
      brain injury. The aim of this study was to assess the selective sigma-1 receptor
      agonist 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate (PRE-084) in models of
      inflammation-sensitized hyperoxia-induced developing brain injury. For in vivo
      studies, rat pups were randomly presensitized with 1) lipopolysaccharide or 2)
      vehicle on postnatal day 3. On day 6, pups received either 1) PRE-084 or 2)
      vehicle and were subsequently exposed to hyperoxic conditions for 6, 12, or 24
      hr. At the end of exposure, animals were sacrificed and brains were processed for
      caspase-3 analysis using immunohistochemistry and Western blotting. For in vitro
      studies, oligodendroglial cells were subjected to hyperoxic conditions in the
      presence or absence of proinflammatory cytokines and PRE-084. Cell membrane
      integrity and cell viability were assessed by means of lactate dehydrogenase and
      2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT)
      assays. Inflammatory presensitization significantly increased hyperoxia-induced
      injury both in vivo and in vitro. PRE-084 administration did not attenuate
      damage. Sigma-1 receptor agonists have been described as a promising therapeutic
      strategy for brain injury. We were not able to confirm this in the present model.
      The exact mechanisms of action of sigma-1 receptor agonists as well as the
      pathophysiologic pathways involved in hyperoxia-induced injury in the developing
      brain remain to be elucidated.

PMID- 24038157
TI  - Antioxidant and vitamin E transport genes and risk of high-grade prostate cancer
      and prostate cancer recurrence.
AB  - BACKGROUND: Observational studies suggest an inverse association between vitamin
      E and risk of prostate cancer, particularly aggressive tumors. However, three
      large randomized controlled trials have reported conflicting results. Thus, we
      examined circulating vitamin E and vitamin E-related genes in relation to risk of
      high-grade prostate cancer and prostate cancer recurrence among men initially
      diagnosed with clinically organ-confined disease. METHODS: We measured
      circulating alpha- and gamma-tocopherol and genotyped 30 SNPs in SOD1, SOD2,
      SOD3, TTPA, and SEC14L2 among 573 men with organ-confined prostate cancer who
      underwent radical prostatectomy. We examined associations between circulating
      vitamin E, genotypes, and risk of high-grade prostate cancer (Gleason grade >= 8
      or 7 with primary score >= 4; n = 117) using logistic regression, and risk of
      recurrence (56 events; 3.7 years median follow-up) using Cox proportional hazards
      regression. RESULTS: Circulating gamma-tocopherol was associated with an
      increased risk of high-grade prostate cancer (Q4 v. Q1 odds ratio [OR] = 1.87;
      95% confidence intervals [CI]: 0.97-3.58; P trend =0.02). The less common allele
      in SOD3 rs699473 was associated with an increased risk of high-grade disease (T >
      C: OR = 1.40, 95% CI: 1.04-1.89). Two independent SNPs in SOD1 were inversely
      associated with prostate cancer recurrence in additive models (rs17884057 hazard
      ratio [HR] = 0.49, 95%CI: 0.25-0.96; rs9967983 HR = 0.62, 95% CI: 0.40-0.95).
      CONCLUSIONS: Among men with clinically organ-confined prostate cancer, genetic
      variation in SOD may be associated with risk of high-grade disease at diagnosis
      and disease recurrence. Circulating gamma-tocopherol levels may also be
      associated with an increased risk of high-grade disease at diagnosis.

PMID- 24038158
TI  - Molecular impact of juvenile hormone agonists on neonatal Daphnia magna.
AB  - Daphnia magna has been used extensively to evaluate organism- and population
      level responses to pollutants in acute toxicity and reproductive toxicity tests.
      We have previously reported that exposure to juvenile hormone (JH) agonists
      results in a reduction of reproductive function and production of male offspring
      in a cyclic parthenogenesis, D. magna. Recent advances in molecular techniques
      have provided tools to understand better the responses to pollutants in aquatic
      organisms, including D. magna. DNA microarray was used to evaluate gene
      expression profiles of neonatal daphnids exposed to JH agonists: methoprene (125,
      250 and 500 ppb), fenoxycarb (0.5, 1 and 2 ppb) and epofenonane (50, 100 and 200
      ppb). Exposure to these JH analogs resulted in chemical-specific patterns of gene
      expression. The heat map analyses based on hierarchical clustering revealed a
      similar pattern between treatments with a high dose of methoprene and with
      epofenonane. In contrast, treatment with low to middle doses of methoprene
      resulted in similar profiles to fenoxycarb treatments. Hemoglobin and JH epoxide
      hydrolase genes were clustered as JH-responsive genes. These data suggest that
      fenoxycarb has high activity as a JH agonist, methoprene shows high toxicity and
      epofenonane works through a different mechanism compared with other JH analogs,
      agreeing with data of previously reported toxicity tests. In conclusion, D. magna
      DNA microarray is useful for the classification of JH analogs and identification
      of JH-responsive genes.

PMID- 24038159
TI  - CMV and cardiovascular disease: reply.

PMID- 24038160
TI  - Cytomegalovirus and cardiovascular disease--the importance of covariates.

PMID- 24038161
TI  - Molecular cloning and transcription expression of 3-dehydroecdysone 3alpha
      reductase (3de 3alpha-reductase) in the different tissues and the developing
      stage from the silkworm, Bombyx mori L.
AB  - Molting in insects is regulated by molting hormones (ecdysteroids), which are
      also crucial to insect growth, development, and reproduction etc. The decreased
      ecdysteroid in titre results from enhanced ecdysteroid inactivation reactions
      including the formation of 3-epiecdyson under ecdysone oxidase and 3
      dehydroecdysone 3alpha-reductase (3DE 3alpha-reductase). In this paper, we cloned
      and characterized 3-dehydroecdysone 3alpha-reductase (3DE 3alpha-reductase) in
      different tissues and developing stage of the silkworm, Bombyx mori L. The B.
      mori 3DE 3alpha-reductase cDNA contains an ORF 783 bp and the deduced protein
      sequence containing 260 amino acid residues. Analysis showed the deduced 3DE
      3alpha-reductase belongs to SDR family, which has the NAD(P)-binding domain.
      Using the Escherichia coli, a high level expression of a fusion polypeptide band
      of approx. 33 kDa was observed. High transcription of 3DE 3alpha-reductase was
      mainly presented in the midgut and hemolymph in the third day of fifth instar
      larvae in silkworm. The expression of 3DE 3alpha-reductase at different stages of
      larval showed that the activity in the early instar was high, and then reduced in
      late instar. This is parallel to the changes of molting hormone titer in larval.
      3DE 3alpha-reductase is key enzyme in inactivation path of ecdysteroid. The data
      elucidate the regulation of 3DE 3alpha-reductase in ecdyteroid titer of its
      targeting organs and the relationship between the enzyme and metamorphosis. 

PMID- 24038162
TI  - Understanding universal adsorption limits for hydrogen storage in nano porous
      systems.
AB  - Despite of more than 15 years of research, no materials possess the adsorbing
      properties required for mobile storage. At this time of state-of-the-art
      technology, the essential question should be asked: why is it so difficult to
      prepare a material with the desired properties? Here, we discuss the sources of
      physical limitations of existing materials and indicate the directions for
      further material research. 

PMID- 24038163
TI  - Modafinil and armodafinil improve attention and global mental status in Lewy
      bodies disorders: preliminary evidence.

PMID- 24038164
TI  - Ten year serial mean corpuscular volume--a peripheral marker for Alzheimer's
      disease in Down syndrome.

PMID- 24038165
TI  - Increase in blood pressure precedes clinical depression in elderly primary care
      patients.

PMID- 24038166
TI  - Effects of freely accessible computerized test systems on the spontaneous
      behaviors and stress level of Guinea baboons (Papio papio).
AB  - Fagot and Paleressompoulle [Fagot and Paleressompoulle (2009) Behav Res Methods
      41: 396-404] described a new automated learning device for monkeys (ALDM) to test
      the cognitive functions of nonhuman primates within their social groups. However,
      the impact of the ALDM procedure on animal well-being needs to be investigated.
      The present study assessed the consequences of ALDM testing on the behavioral
      repertoire of Guinea baboons (Papio papio) and their stress levels as inferred
      from measurements of saliva cortisol. Accessibility to ALDM test computers
      reduced the number of resting periods as well as the number of stereotypies.
      Lower cortisol levels were also found during ALDM testing. These findings and
      others demonstrate that ALDM testing has a positive impact on animal well-being
      and can be considered as a means for behavioral enrichment in captive primates.

PMID- 24038167
TI  - Size of blood pressure reduction from renal denervation: insights from meta
      analysis of antihypertensive drug trials of 4,121 patients with focus on trial
      design: the CONVERGE report.
AB  - OBJECTIVE: 30 mm Hg drops in office systolic blood pressure are reported in
      trials of renal denervation, but ambulatory reductions are much smaller. This
      disparity is assumed to have a physiological basis and also be present with
      antihypertensive drugs. DESIGN: We examine this office-ambulatory discrepancy
      through meta-analysis of drug and denervation trials, categorising by trial
      design. PATIENTS (STUDIES): 31 drug trials enrolling 4121 patients and 23 renal
      denervation trials enrolling 720 patients met the criteria. RESULTS: In drug
      trials without randomisation or blinding, pressure reductions are 5.6 mm Hg (95%
      CI 2.98 to 8.22 mm Hg) larger on office measurements than ambulatory blood
      pressure monitoring (p<0.0001). By contrast, with randomisation and blinding,
      office reductions are identical to ambulatory reductions (difference -0.88 mm Hg,
      95% CI -3.18 to 1.43, p=0.45). For renal denervation, there are no randomised
      blinded trial results. In unblinded trials, office pressure drops were 27.6 mm Hg
      versus pretreatment, and 26.6 mm Hg versus unintervened controls. By contrast,
      ambulatory pressure drops averaged 15.7 mm Hg across all trials. Among those
      where the baseline ambulatory pressure was not the deciding factor for enrolment
      (avoiding regression to the mean), ambulatory drops averaged only 11.9 mm Hg.
      CONCLUSIONS: Discrepancies in drug trials between office and ambulatory blood
      pressure reductions disappear once double-blinded placebo control is implemented.
      Renal denervation trials may also undergo similar evolution. We predict that as
      denervation trial designs gradually improve in bias-resistance, office and
      ambulatory pressure drops will converge. We predict that it is the office drops
      that will move to match the ambulatory drops, that is, not 30, but nearer 13.

PMID- 24038168
TI  - Fatal venous thromboembolism associated with hospital admission: a cohort study
      to assess the impact of a national risk assessment target.
AB  - OBJECTIVES: In 2010, the Department of Health in England introduced an
      incentivised national target for National Health Service (NHS) hospitals aiming
      to increase the number of patients assessed for the risk of developing venous
      thromboembolism (VTE) associated with hospital admission. We assessed the impact
      of this initiative on VTE mortality and subsequent readmission with non-fatal
      VTE. DESIGN: Observational cohort study. PATIENTS: All patients admitted to NHS
      hospitals in England between July 2010 and March 2012. INTERVENTIONS: An NHS
      hospital which assessed at least 90% of patient admissions achieved the quality
      standard. MAIN OUTCOME MEASURES: The principal outcome measured was death from
      VTE up till 90 days after hospital discharge using linked Office of National
      Statistics and Hospital Episode Statistics data. RESULTS: In the principal
      analyses of patients admitted to hospital for more than 3 days, there was a
      statistically significant reduction in VTE deaths in hospitals achieving 90% VTE
      risk assessment: relative risk (RR) 0.85 (95% CI 0.75 to 0.96; p=0.011) for VTE
      as the primary cause of death. In supportive analyses of postdischarge deaths
      after index admissions of up to 3 days, there was also a reduction in fatal VTE
      RR 0.61 (0.48 to 0.79; p=0.0002). This effect was seen for both surgical and non
      surgical patients. No effect was seen in day case admissions. There was no change
      in non-fatal VTE readmissions up to 90 days after discharge. CONCLUSIONS: A
      national quality initiative to increase the number of hospitalised patients
      assessed for risk of VTE has resulted in a reduction in VTE mortality.

PMID- 24038169
TI  - Aminopyridinate-FI hybrids, their hafnium and titanium complexes, and their
      application in the living polymerization of 1-hexene.
AB  - Based on two well-established ligand systems, the aminopyridinato (Ap) and the
      phenoxyimine (FI) ligand systems, new Ap-FI hybrid ligands were developed. Four
      different Ap-FI hybrid ligands were synthesized through a simple condensation
      reaction and fully characterized. The reaction of hafnium tetrabenzyl with all
      four Ap-FI hybrid ligands exclusively led to mono(Ap-FI) complexes of the type
      [(Ap-FI)HfBn2 ]. The ligands acted as tetradentate dianionic chelates. Upon
      activation with tris(pentafluorophenyl)borane, the hafnium-dibenzyl complexes led
      to highly active catalysts for the polymerization of 1-hexene. Ultrahigh
      molecular weights and extremely narrow polydispersities support the living nature
      of this polymerization process. A possible deactivation product of the hafnium
      catalysts was characterized by single-crystal X-ray analysis and is discussed.
      The coordination modes of these new ligands were studied with the help of model
      titanium complexes. The reaction of titanium(IV) isopropoxide with ligand 1 led
      to a mono(Ap-FI) complex, which showed the desired fac-mer coordination mode.
      Titanium (IV) isopropoxide reacted with ligand 4 to give a complex of the type
      [(ApH-FI)2 Ti(OiPr)2 ], which featured the ligand in its monoanionic form. The
      two titanium complexes were characterized by X-ray crystal-structure analysis. 

PMID- 24038170
TI  - Transduction of proteins into leishmania tarentolae by formation of non-covalent
      complexes with cell-penetrating peptides.
AB  - Cell-penetrating peptides (CPPs) are used to transport peptides, proteins,
      different types of ribonucleic acids (or mimics of these molecules), and DNA into
      live cells, both plant and mammalian. Leishmania belongs to the class of protozoa
      having, in comparison to mammalian cells, a different lipid composition of the
      membrane, proteoglycans on the surface, and signal pathways. We investigated the
      uptake of two different and easily detectable proteins into the non-pathogenic
      strain Leishmania tarentolae. From the large number of CPPs available, six and a
      histone were chosen specifically for their ability to form non-covalent
      complexes. For Leishmania we used the enzyme beta-galactosidase and fluorescent
      labeled bovine serum albumin as cargoes. The results are compared to similar
      internalization studies using mammalian cells [Mussbach et al., ]. Leishmania
      cells can degrade CPPs by a secreted and membrane-bound chymotrypsin-like
      protease. Both cargo proteins were internalized with sufficient efficiency and
      achieved intramolecular concentrations similar to mammalian cells. The transport
      efficiencies of the CPPs differed from each other, and showed a different rank
      order for both cargoes. The intracellular distribution of fluorescent-labeled
      bovine serum albumin showed highest concentrations in the nucleus and
      kinetoplast. Leishmania are susceptible to high concentrations of some CPPs,
      although comparably dissimilar to mammalian cells. MPG-peptides are more
      cytotoxic in Leishmania than in mammalian cells, acting as antimicrobial
      peptides. Our results contribute to a better understanding of molecular
      interactions in Leishmania cells and possibly to new treatments of leishmaniasis.

PMID- 24038171
TI  - Chiral ditopic cyclophosphazane (CycloP) ligands: synthesis, coordination
      chemistry, and application in asymmetric catalysis.
AB  - A series of dichlorocyclophosphazanes [{ClP(MU-NR)}2 ] containing chiral and
      achiral R groups was obtained from simple commercially available amines and PCl3
      . Their condensation reactions with axially chiral biaryl diols yielded ansa
      bridged chiral cyclophosphazane (CycloP) ligands. This highly modular methodology
      allows extensive elaboration of the ligand set, in which the chirality can be
      introduced at the diol bridge and/or the amido R group. This provides the
      possibility to observe match and mismatch effects in catalysis. A series of
      twenty CycloP ligands was synthesized and characterized by multinuclear NMR
      spectroscopy, HRMS, elemental analysis, and in selected cases, single-crystal X
      ray diffraction. These studies show that all of the ditopic CycloP ligands are C2
      symmetric, rendering their metal coordination sites symmetry equivalent. Two well
      established enantioselective reactions were explored by using late-transition
      metal CycloP complexes as catalysts; the gold-catalyzed hydroamination of gamma
      allenyl sulfonamides and the asymmetric nickel-catalyzed three-component coupling
      of a diene and an aldehyde. The steric demands of the CycloP ligands have a
      subtle influence on the reactivity and selectivity observed in both reactions.
      Good enantiomeric ratios (e.r.) as high as 89:11 in the gold-catalyzed reaction
      and 92:8 in the nickel-catalyzed bis-homoallylation reaction were observed. 

PMID- 24038172
TI  - 25th anniversary article: Understanding the lithiation of silicon and other
      alloying anodes for lithium-ion batteries.
AB  - Alloying anodes such as silicon are promising electrode materials for next
      generation high energy density lithium-ion batteries because of their ability to
      reversibly incorporate a high concentration of Li atoms. However, alloying anodes
      usually exhibit a short cycle life due to the extreme volumetric and structural
      changes that occur during lithium insertion/extraction; these transformations
      cause mechanical fracture and exacerbate side reactions. To solve these problems,
      there has recently been significant attention devoted to creating silicon
      nanostructures that can accommodate the lithiation-induced strain and thus
      exhibit high Coulombic efficiency and long cycle life. In parallel, many
      experiments and simulations have been conducted in an effort to understand the
      details of volumetric expansion, fracture, mechanical stress evolution, and
      structural changes in silicon nanostructures. The fundamental materials knowledge
      gained from these studies has provided guidance for designing optimized Si
      electrode structures and has also shed light on the factors that control large
      volume change solid-state reactions. In this paper, we review various fundamental
      studies that have been conducted to understand structural and volumetric changes,
      stress evolution, mechanical properties, and fracture behavior of nanostructured
      Si anodes for lithium-ion batteries and compare the reaction process of Si to
      other novel anode materials. 

PMID- 24038173
TI  - Posterior tibiotalar ligament: an anatomic study correlated with MRI.
AB  - This study was performed to clarify the morphologic characteristics of two layers
      of the posterior tibiotalar ligament (PTT) and two bands of the deep PTT (dPTT),
      and to correlate the dissection findings with MR images. Sixty-four ankles from
      42 cadavers were examined. The origin and insertion sites of the superficial PTT
      (sPTT) and the two bands of the dPTT were identified, and their length, width,
      and thickness were measured. MRI was performed on four ankles before serial
      sectioning or dissection. The serial sections were taken at a thickness of 2 mm.
      The sPTT was observed in 50 out of 60 dissected specimens (83.3%), taken from 64
      ankles of 42 cadavers. The dPTT was observed in all specimens. The sPTT,
      superficial band of the dPTT (sdPTT), and deep band of the dPTT (ddPTT) arose
      from the inferior surface of the medial malleolus. The sPTT attached to the
      posterior process of the talus, and the sdPTT and ddPTT attached to the
      depression below the articular facet for the medial malleolus. The sPTT and two
      bands of the dPTT could be distinguished on coronal MR images, where the sPTT
      appeared as a thin string superficial to the two bands of the dPTT, which were
      separated as two thick, low-density strings. In the coronal plane of frozen
      sections, the outermost sPTT appeared as a thin, white bundle attached to the
      sdPTT. The PTT is composed of superficial and deep layers, and the dPTT is
      composed of superficial and deep bands.

PMID- 24038174
TI  - Tetraspanins are involved in Schwann cell-axon interaction.
AB  - Many studies have shown that tetraspanins play important role in cell-cell and
      cell-extracellular matrix (ECM) interactions. The repertoire and functions of
      tetraspanins in Schwann cells, glial cells of the peripheral nervous system have
      remained largely uncharacterized. This study was undertaken to identify Schwann
      cell tetraspanins and to elucidate their possible functions. Microarray analysis
      revealed the expression of numerous tetraspanins in primary culture of Schwann
      cells. Expression of five of them, CD9, CD63, CD81, CD82, and CD151, and of
      tetraspanin-associated protein EWI-2 was also confirmed by immunofluorescence.
      Localization of CD9, CD63, CD81, and EWI-2 was largely confined to paranodes and
      Schmidt-Lanterman incisures, regions of noncompact myelin. Immunoprecipitation
      experiments showed that these four proteins form a complex in Schwann cells.
      siRNA silencing of individual components of the complex did not affect Schwann
      cell adhesion to ECM proteins or attachment to and alignment with axons. However,
      suppression of both CD63 and CD81 expression together significantly inhibited
      extension of Schwann cell processes along axons, without affecting initial
      attachment of the cells to the axonal surface. Adhesion, spreading, and migration
      of Schwann cells on ECM proteins also were not affected by double silencing of
      CD63 and CD81. Suppression of CD63 and CD81 expression did not affect the ability
      of Schwann cells to myelinate dorsal root ganglion neurons in vitro. These
      findings strongly suggest that CD63 and CD81 play an important role in Schwann
      cell spreading along axons but seem to be dispensable for Schwann cell
      myelination.

PMID- 24038175
TI  - Optimal two-phase sampling design for comparing accuracies of two binary
      classification rules.
AB  - In this paper, we consider the design for comparing the performance of two binary
      classification rules, for example, two record linkage algorithms or two screening
      tests. Statistical methods are well developed for comparing these accuracy
      measures when the gold standard is available for every unit in the sample, or in
      a two-phase study when the gold standard is ascertained only in the second phase
      in a subsample using a fixed sampling scheme. However, these methods do not
      attempt to optimize the sampling scheme to minimize the variance of the
      estimators of interest. In comparing the performance of two classification rules,
      the parameters of primary interest are the difference in sensitivities,
      specificities, and positive predictive values. We derived the analytic variance
      formulas for these parameter estimates and used them to obtain the optimal
      sampling design. The efficiency of the optimal sampling design is evaluated
      through an empirical investigation that compares the optimal sampling with simple
      random sampling and with proportional allocation. Results of the empirical study
      show that the optimal sampling design is similar for estimating the difference in
      sensitivities and in specificities, and both achieve a substantial amount of
      variance reduction with an over-sample of subjects with discordant results and
      under-sample of subjects with concordant results. A heuristic rule is recommended
      when there is no prior knowledge of individual sensitivities and specificities,
      or the prevalence of the true positive findings in the study population. The
      optimal sampling is applied to a real-world example in record linkage to evaluate
      the difference in classification accuracy of two matching algorithms.

PMID- 24038176
TI  - Pesticides present in migrant farmworker housing in North Carolina.
AB  - BACKGROUND: Migrant farmworkers are exposed to pesticides at work. Housing
      provided to migrant farmworkers may also expose them to pesticides, increasing
      their health risks. This analysis (1) describes the presence of organophosphorous
      (OP) and pyrethroid pesticides in North Carolina migrant farmworker houses, and
      (2) delineates associations of farmworker camp characteristics with pesticide
      detection and concentration. METHODS: In 2010, 186 migrant farmworkers camps in
      NC were recruited (participation rate of 82.3%); pesticide wipe samples for 176
      houses were analyzed. Tobacco is the predominant hand-harvested crop in this
      region. Two farmworkers per camp completed interviews; a third assisted with a
      housing inspection. Gas chromatography-mass spectrometry was used to detect OP
      and pyrethroid pesticides. Covariates of pesticide detection and concentration
      were determined with ANOVA and Tobit regression. RESULTS: OPs were found in 166
      of 176 houses (average of 2.4/house); pyrethroids were found in 171 houses
      (average of 4.3/house). The number of different OPs detected in each camp and
      concentrations of these OPs were not associated with camp and housing
      characteristics. The number of different pyrethroids detected in each camp and
      concentrations of these pyrethroids were associated with camps having residents
      with H2-A visas, a posted North Carolina Department of Labor Certificate of
      Inspection, no barracks, fewer residents, no bedroom weather protection or floor
      violations, and no roaches. CONCLUSIONS: Farmworkers are exposed to pesticides
      where they live. Policy on removing pesticides from farmworker houses is needed.
      Reducing pesticides in farmworker houses will reduce one health risk confronted
      by this vulnerable population.

PMID- 24038177
TI  - Acute lower urinary tract dysfunction (LUTD) following traumatic brain injury
      (TBI) in rats.
AB  - AIMS: The aim of this study was to assess experimental traumatic brain injury
      (TBI)-induced lower urinary tract dysfunction (LUTD) by monitoring systemic and
      urodynamic parameters using an implantable telemetry system. METHODS: A single
      lateral fluid percussion TBI (FP-TBI; 3.4 atm) was administered to 10 female
      rats. Pressure micro-catheters were implanted in the abdominal aorta and bladder
      dome for simultaneous data recording. Hemodynamic and urodynamic variables
      recorded 24 hr before and 24 hr after injury were analyzed and compared. RESULTS:
      TBI in the acute phase resulted in LUTD affecting bladder emptying, characterized
      by failure of voiding reflex, high capacity bladder, increased voided volume,
      prolonged intermicturition intervals, and loss of compliance. The dominant
      symptom was urinary retention (100%) and incontinence (60%). The effects followed
      a pattern of initial loss of bladder function followed by either altered recovery
      of reflex micturition or a period of incontinence. With a moderate injury
      symptoms were temporary in 90% of animals and permanent in 10% of animals. Injury
      produced only transient hypertension (<=1 hr) with a maximum systolic pressure of
      172.64 +/- 14.53 mmHg (70% of animals). CONCLUSIONS: The results demonstrate that
      experimental FP-TBI causes temporary bladder dysfunction that in more severe
      cases becomes permanent. Telemetry recordings revealed a sequence of events
      following injury that establishes moderate TBI as a risk factor for neurogenic
      bladder disorder. Results also suggest a correlation between lateral FP-TBI and
      incontinence.

PMID- 24038178
TI  - The metabolic function of hepatocytes differentiated from human mesenchymal stem
      cells is inversely related to cellular glutathione levels.
AB  - Differentiation of mesenchymal stem cells (MSCs) to hepatocytes-like cells is
      associated with alteration in the level of reactive oxygen species (ROS) and
      antioxidant defense system. Here, we report the role of glutathione in the
      functions of hepatocytes derived from MSCs. The stem cells undergoing
      differentiation were treated with glutathione modifiers [buthionine sulfoxide
      (BSO) or N-acetyl cysteine (NAC)], and hepatocytes were collected on day 14 of
      differentiation and analysed for their biological and metabolic functions.
      Differentiation process has been performed in presence of glutathione modifiers
      viz. BSO and NAC. Depending on the level of cellular glutathione, the
      proliferation rate of MSCs was affected. Glutathione depletion by BSO resulted in
      increased levels of albumin and ROS in hepatocytes. Whereas, albumin and ROS were
      inhibited in cells treated with glutathione precursor (NAC). The metabolic
      function of hepatocytes was elevated in BSO-treated cells as judged by increased
      urea, transferrin, albumin, alanine transaminase and aspartate transaminase
      secretions in the media. However, the metabolic activity of the hepatocytes was
      inhibited when glutathione was increased by NAC. We conclude that the efficiency
      of metabolic function of hepatocytes is inversely related to the levels of
      cellular glutathione. These data may suggest a novel role of glutathione in
      regulation of metabolic function of hepatocytes.

PMID- 24038179
TI  - Neglected tropical disease control in post-war Sierra Leone using the
      Onchocerciasis Control Programme as a platform.
AB  - Strategic investments in the control of neglected tropical diseases (NTD)
      spearheaded by the US Government, the British Government and other bilateral
      donors such as foundations and key pharmaceutical partners have enabled the
      treatment of millions of people for the five targeted debilitating diseases
      (lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted
      helminthiasis and trachoma), paving the way for the potential elimination as
      public health problems of some of these diseases. Like many other countries,
      Sierra Leone has a high burden of these major NTDs. Despite the fragile
      infrastructure of a health system emerging from a devastating 10-year civil war,
      the country has successfully implemented the National NTD Control Programme,
      reaching national coverage in 2010. The NTD Control Programme uses the existing
      Onchocerciasis Control Programme as a platform and involves primary health
      workers. The programme has provided extensive training opportunities to health
      workers at national, district and community levels. The country currently has 31
      161 trained community volunteers treating a population of five million people. It
      is shown that the investments in NTD control are not only to control NTDs but
      also to strengthen health systems, particularly at the primary level, through
      extensive capacity building of frontline health workers and community-directed
      distributors. 

PMID- 24038180
TI  - Quality and potential use of data collected during nutrition surveys: an analysis
      of surveys in Ethiopia.
AB  - Humanitarian agencies regularly carry out nutrition surveys to estimate the
      prevalence of acute malnutrition (wasting) and mortality as well as to collect
      data on a wide range of contributory or aggravating factors in order to identify
      interventions and to direct aid where it is most needed. In this study, the case
      of Ethiopia was used (i) to assess the proportion of 291 nutrition surveys
      conducted between 2003 and 2008 that used the recommended sampling method to
      estimate the prevalence of wasting, (ii) to assess how and what data on
      indicators of aggravating factors were collected, (iii) to examine whether data
      on such factors can be used to establish priorities for emergency assistance
      based on Ethiopian Government guidelines and (iv) to discuss the general value of
      such data. All but one survey used the recommended methods to estimate the
      prevalence of wasting. Data were collected on more than 40 indicators of
      aggravating factors related to health, caring practices, food security and coping
      strategies, but no consistent methods or indicators were used, resulting in
      inconsistent data. This illustrates the need to develop and agree upon a set of
      core indicators of aggravating factors and then thresholds to describe the
      humanitarian situation in Ethiopia and elsewhere and to indicate priorities for
      interventions. 

PMID- 24038181
TI  - No cash, no care: how user fees endanger health--lessons learnt regarding
      financial barriers to healthcare services in Burundi, Sierra Leone, Democratic
      Republic of Congo, Chad, Haiti and Mali.
AB  - Although user fees are a common form of healthcare financing in resource-poor
      countries, there is growing consensus that their use compromises health service
      utilisation and population health. Between 2003 and 2006, Medecins sans
      Frontieres (MSF) conducted population-based surveys in Burundi, Sierra Leone,
      Democratic Republic of Congo, Chad, Haiti and Mali to determine the impact of
      user fees on healthcare-seeking behaviour and access. For general and disease
      specific conditions, MSF also measured the impact of (i) reduced payment systems
      in Chad, Mali, Haiti and Burundi and (ii) user fee abolition for certain
      population groups in Burundi and Mali. User fees were found to result in low
      utilisation of public health facilities, exclusion from health care and
      exacerbation of impoverishment, forcing many to seek alternative care. Financial
      barriers affected 30-60% of people requiring health care. Exemption systems
      targeting vulnerable individuals proved ineffective, benefiting only 1-3.5% of
      populations. Alternative payment systems, requiring 'modest' fees from users
      (e.g. low flat fees), did not adequately improve coverage of essential health
      needs, especially for the poorest and most vulnerable. Conversely, user fee
      abolition for large population groups led to rapid increases in utilisation of
      health services and coverage of essential healthcare needs. Abolition of user
      fees appears crucial in helping to reduce existing barriers to health care. The
      challenge for health authorities and donor agencies is around working creatively
      to remove the fees while addressing the financial consequences of improved access
      and providing quality care. 

PMID- 24038182
TI  - Impact of the National Access to Antiretroviral Program on the incidence of
      opportunistic infections in Thailand.
AB  - The National Access to Antiretroviral Program caused a decline in HIV mortality
      in Thailand, but its impact on opportunistic infections (OI) remains unknown. The
      aim of this study was to compare the incidence of different OIs before and after
      the initiation of highly active antiretroviral therapy (HAART). Data from a
      prospective cohort at a hospital in northern Thailand were analysed. In total,
      704 patients enrolled from July 2000 to October 2002 and not on HAART were
      followed up until October 2004. In addition, 409 patients who started HAART
      between April 2002 and January 2004 were followed up for 24 months. The impact of
      HAART on OIs was analysed using Cox proportional hazard models. HAART was
      associated with a strong reduction in OIs. The reduction appeared to vary by
      type: tuberculosis (TB), adjusted hazard ratio (AHR) = 0.2 (95% CI 0.1-0.5);
      pneumocystis pneumonia (PCP), AHR = 0.03 (95% CI 0.007-0.1); cryptococcal
      meningitis, AHR = 0.2 (95% CI 0.1-0.5); and penicilliosis, AHR = 0.1 (95% CI 0.06
      0.3). In conclusion, HAART was very effective in reducing OIs, especially PCP. TB
      and cryptococcal meningitis remained frequent in the early phase of
      antiretroviral drug therapy. More attention to prophylaxis as well as earlier
      diagnosis and starting treatment for these OIs is recommended. 

PMID- 24038183
TI  - Strengths and weaknesses of the humanitarian Cluster Approach in relation to
      sexual and reproductive health services in northern Uganda.
AB  - Implementation of the Cluster Approach has been a major recent development in the
      humanitarian system. The aim of this study was to explore the strengths and
      weaknesses of the humanitarian Cluster Approach in relation to services for
      sexual and reproductive health (SRH) [including gender-based violence (GBV)] in
      northern Uganda, which is recovering from over 20 years of armed conflict. Face
      to-face and telephone, semistructured, qualitative interviews were conducted in
      2009 with purposively selected key informants from governmental, non
      governmental, United Nations and donor agencies working in northern Uganda.
      Respondents noted a number of contributions of the Cluster Approach, including
      improved co-ordination of SRH services and stronger advocacy. However, concerns
      were raised about the low prioritisation, limited leadership and capacity, and
      standard setting for SRH services. Concerns were also raised about limited
      planning and capacity for dissolution of the Clusters in the transition to
      recovery and development in northern Uganda. Despite a number of contributions
      made by the Cluster Approach, particularly for responding to GBV, there were many
      concerns about its limited influence on SRH services. There were also concerns
      that the transition to recovery and development in northern Uganda may not result
      in reproductive health services being sufficiently strengthened. 

PMID- 24038184
TI  - Abundance and prevalence of Aedes aegypti immatures and relationships with
      household water storage in rural areas in southern Viet Nam.
AB  - Since 2000, the Government of Viet Nam has committed to provide rural communities
      with increased access to safe water through a variety of household water supply
      schemes (wells, ferrocement tanks and jars) and piped water schemes. One
      possible, unintended consequence of these schemes is the concomitant increase in
      water containers that may serve as habitats for dengue mosquito immatures,
      principally Aedes aegypti. To assess these possible impacts we undertook detailed
      household surveys of Ae. aegypti immatures, water storage containers and various
      socioeconomic factors in three rural communes in southern Viet Nam. Positive
      relationships between the numbers of household water storage containers and the
      prevalence and abundance of Ae. aegypti immatures were found. Overall, water
      storage containers accounted for 92-97% and 93-96% of the standing crops of
      III/IV instars and pupae, respectively. Interestingly, households with higher
      socioeconomic levels had significantly higher numbers of water storage containers
      and therefore greater risk of Ae. aegypti infestation. Even after provision of
      piped water to houses, householders continued to store water in containers and
      there was no observed decrease in water storage container abundance in these
      houses, compared to those that relied entirely on stored water. These findings
      highlight the householders' concerns about the limited availability of water and
      their strong behavoural patterns associated with storage of water. We conclude
      that household water storage container availability is a major risk factor for
      infestation with Ae. aegypti immatures, and that recent investment in rural water
      supply infrastructure are unlikely to mitigate this risk, at least in the short
      term. 

PMID- 24038185
TI  - Assessing the need for training: general practitioners' knowledge, attitude and
      practice concerning dengue and malaria in Karachi, Pakistan.
AB  - Changing environmental conditions have increased the transmission period for both
      dengue and malaria. Annual incidence of malaria in 2006 alone was 247 million
      cases leading to nearly 881 000 deaths; whereas another 50 to 100 million dengue
      infections, associated with an overall mortality of 2.5%, are expected each year.
      In Pakistan, like many developing nations with endemic malaria, an empirical
      clinical diagnosis is usually made, due to a lack of resources and availability
      of diagnostic facilities. Since both diseases are endemic in the same population
      and presenting symptoms are similar a thorough knowledge of both diseases is
      essential for improving diagnosis on clinical grounds. Thus our study aims were
      to evaluate knowledge, attitudes and practices of family medicine practitioners
      with regard to dengue and malaria and thereby assess the need for further
      training. Ninety consenting general practitioners (GPs) in different towns of
      Karachi, Pakistan were administered an extensive questionnaire of 50 questions
      regarding their knowledge, attitudes and practices on management of dengue and
      malaria. The authors concluded that despite possessing basic knowledge of the
      disease, the majority of GPs in the area needed training regarding both diseases
      and their management. Key targets identified for training programs included
      clinical diagnosis and management of endemic vector borne diseases. 

PMID- 24038186
TI  - Knowledge, attitudes and practices of Trinidadian households regarding
      leptospirosis and related matters.
AB  - Leptospirosis is a zoonotic disease that is underreported in many countries,
      including Trinidad and Tobago, because of a low level of awareness of the
      disease. A knowledge, attitudes and practices (KAP) survey concerning
      leptospirosis was carried out on 800 households throughout Trinidad to determine
      the level of awareness of the disease in the country. Of the participants, 52.4%
      had heard of leptospirosis but approximately half of these did not know any signs
      or symptoms of the disease. Knowledge of leptospirosis was not related to level
      of education of people, but to geographical location. Approximately 82% of
      participants were involved in at least one risk activity, the most common of
      which was walking barefooted outdoors. The animal which most participants were in
      contact with was the dog. Of the 53% of participants who had seen a mouse or rat
      around the house, 5% utilized the free control services of the regional
      corporation. Approximately 66% of participants were not satisfied with the
      services provided by the regional corporation. There was a positive attitude
      towards general health and good sanitary practices among the Trinidad population,
      but there was also a lack of knowledge of leptospirosis. The low level of
      awareness of leptospirosis in Trinidad makes it a disease of public health
      importance, as it is often mistaken for dengue which is more well-known in the
      country. 

PMID- 24038187
TI  - Search for highly efficient, stereoselective, and practical synthesis of complex
      organic compounds of medicinal importance as exemplified by the synthesis of the
      C21-C37 fragment of amphotericin B.
AB  - Highly stereoselective: A highly efficient, stereoselective and practical
      synthesis of the C21-C37 fragment of amphotericin B was realized in 25 % overall
      yield in eight longest linear steps from commercially available ethyl (S)-3
      hydroxybutyrate by using Frater-Seebach alkylation, Brown crotylboration, Negishi
      coupling, Heck reaction, and Horner-Wadsworth-Emmons (HWE) olefination as key
      steps (see diagram).

PMID- 24038188
TI  - Oxaphospholes and bisphospholes from phosphinophosphonates and alpha,beta
      unsaturated ketones.
AB  - The reaction of a {W(CO)5 }-stabilized phosphinophosphonate 1, (CO)5
      WPH(Ph)?P(O)(OEt)2 , with ethynyl- (2 a-f) and diethynylketones (7-11, 18, and
      19) in the presence of lithium diisopropylamide (LDA) is examined. Lithiated 1
      undergoes nucleophilic attack in the Michael position of the acetylenic ketones,
      as long as this position is not sterically encumbered by bulky (iPr)3 Si
      substituents. Reaction of all other monoacetylenic ketones with lithiated 1
      results in the formation of 2,5-dihydro-1,2-oxaphospholes 3 and 4. When
      diacetylenic ketones are employed in the reaction, two very different product
      types can be isolated. If at least one (Me)3 Si or (Et)3 Si acetylene terminus is
      present, as in 7, 8, and 19, an anionic oxaphosphole intermediate can react
      further with a second equivalent of ketone to give cumulene-decorated
      oxaphospholes 14, 15, 24, and 25. Diacetylenic ketones 10 and 11, with two
      aromatic acetylene substituents, react with lithitated 1 to form exclusively
      ethenyl-bridged bisphospholes 16 and 17. Mechanisms that rationalize the
      formation of all heterocycles are presented and are supported by DFT
      calculations. Computational studies suggest that thermodynamic, as well as
      kinetic, considerations dictate the observed reactivity. The calculated reaction
      pathways reveal a number of almost isoenergetic intermediates that follow after
      ring opening of the initially formed oxadiphosphetane. Bisphosphole formation
      through a carbene intermediate G is greatly favored in the presence of phenyl
      substituents, whereas the formation of cumulene-decorated oxaphospholes is more
      exothermic for the trimethylsilyl-containing substrates. The pathway to the
      latter compounds contains a 1,3-shift of the group that stems from the acetylene
      terminus of the ketone substrates. For silyl substituents, the 1,3-shift proceeds
      along a smooth potential energy surface through a transition state that is
      characterized by a pentacoordinated silicon center. In contrast, a high-lying
      transition state TS(E'-F')R=Ph of 37 kcal mol(-1) is found when the substituent
      is a phenyl group, thus explaining the experimental observation that aryl
      terminated diethynylketones 10 and 11 exclusively form bisphospholes 16 and 17. 

PMID- 24038189
TI  - Identification of the vitamin D receptor in osteoblasts and chondrocytes but not
      osteoclasts in mouse bone.
AB  - Bone is clearly a target of vitamin D and as expected, the vitamin D receptor
      (VDR) is expressed in osteoblasts. However, the presence of VDR in other cells
      such as osteocytes, osteoclasts, chondroclasts, and chondrocytes is uncertain.
      Because of difficulties in obtaining sections of undecalcified adult bone,
      identification of the site of VDR expression in adult bone tissue has been
      problematic. In addition, the antibodies to VDR used in previous studies lacked
      specificity, a property crucial for unambiguous conclusions. In the present
      study, VDR in the various cells from neonatal and adult mouse bone tissues was
      identified by a highly specific and sensitive immunohistochemistry method
      following bone decalcification with EGTA. For accurate evaluation of weak
      immunosignals, samples from Demay VDR knockout mice were used as negative
      control. Molecular markers were used to identify cell types. Our results showed
      that EGTA-decalcification of bone tissue had no detectable effect on the
      immunoreactivity of VDR. VDR was found in osteoblasts and hypertrophic
      chondrocytes but not in the multinucleated osteoclasts, chondroclasts, and bone
      marrow stromal cells. Of interest is the finding that immature osteoblasts
      contain large amounts of VDR, whereas the levels are low or undetectable in
      mature osteoblasts including bone lining cells and osteocytes. Proliferating
      chondrocytes appear devoid of VDR, although low levels were found in the
      hypertrophic chondrocytes. These data demonstrate that osteoblasts and
      chondrocytes are major targets of 1alpha,25-dihydroxyvitamin D, but osteoclasts
      and chondroclasts are minor targets or not at all. A high level of VDR was found
      in the immature osteoblasts located in the cancellous bone, indicating that they
      are major targets of 1alpha,25-dihydroxyvitamin D. Thus, the immature osteoblasts
      are perhaps responsible for the vitamin D hormone signaling resulting in calcium
      mobilization and in osteogenesis.

PMID- 24038190
TI  - Rapid cloning and comparative sequence analysis of full-length cDNA of Rhesus
      monkey (Macaca mulatta) resistin.
AB  - Resistin protein is thought to link insulin resistance in murine models of
      obesity and type-2 diabetes, but the role of resistin in human studies of
      inflammatory metabolic disorders have generated conflicting data. Here, we
      describe the structure of the resistin gene using adipose tissue from non-human
      primates (NHPs), which have been used extensively to model a host of human
      diseases. Full-length cDNA from rhesus macaque resistin obtained by rapid
      amplification of cDNA ends (RACE) is comprised of 526 nucleotides covering an
      open-reading frame (ORF) that encodes a 108-amino-acid protein that is 92%
      homologous with the human counterpart but only 60% homologous with the murine
      counterpart. Using a modified polymerase chain reaction technique, we identified
      single nucleotide polymorphisms and a 78-bp deletion within resistin cDNA of nine
      rhesus macaques. Comparisons of the full-length cDNA sequence and an amplified
      569-bp genomic DNA sequence revealed an error in published predictions arising
      from genomic studies about the gene's exon 3 region. Our data show, for the first
      time, the full-length macaque resistin cDNA sequence (GenBank: JF740676.1). These
      findings will illuminate future studies into the role of resistin in NHP models
      of inflammatory metabolic diseases.

PMID- 24038191
TI  - Cognitive functioning and its influence on sexual behavior in normal aging and
      dementia.
AB  - OBJECTIVE: Motivational aspects, emotional factors, and cognition, all of which
      require intact cognitive functioning may be essential in sexual functioning.
      However, little is known about the association between cognitive functioning and
      sexual behavior. The aim of this article is to review the current evidence for
      the influence of cognitive functioning on sexual behavior in normal aging and
      dementia. METHODS: A systematic literature search was conducted in PubMed, Ovid,
      Cochrane, and PsycINFO databases. The databases were searched for English
      language papers focusing on human studies published relating cognitive
      functioning to sexual behavior in the aging population. Keywords included sexual
      behavior, sexuality, cognitive functioning, healthy elderly, elderly, aging and
      dementia. RESULTS: Eight studies fulfilled our inclusion criteria. Of these
      studies, five included dementia patients and/or their partners, whereas only
      three studies included healthy older persons. Although not consistently, results
      indicated a trend that older people who are not demented and continue to engage
      in sexual activity have better overall cognitive functioning. Cognitive decline
      and dementia seem to be associated with diminished sexual behavior in older
      persons. CONCLUSIONS: The association between cognitive functioning and sexual
      behavior in the aging population is understudied. The results found are
      inconclusive.

PMID- 24038193
TI  - Emerging therapeutics in sleep.
AB  - The development of new therapeutics for sleep disorders is increasingly dependent
      upon understanding the basic brain circuitry that underlies sleep-wake
      regulation, and how it may be pharmacologically manipulated. In this review, we
      consider the pathophysiological basis of major sleep disorders that often are
      seen by neurologists, including excessive daytime sleepiness, insomnia,
      narcolepsy, rapid eye movement sleep behavior disorder, and restless legs
      syndrome, as well as circadian disorders, and we review the current and potential
      future therapeutic approaches.

PMID- 24038194
TI  - CA125-related measures of tumor kinetics and outcome of patients with recurrent
      ovarian cancer receiving chemotherapy: a retrospective evaluation.
AB  - OBJECTIVE: Defining the reliability of cancer antigen-125-related kinetics
      criteria versus Gynecologic Cancer Inter Group criteria in predicting the tumor
      outcome after chemotherapy in patients with recurrent ovarian cancer. METHODS: A
      retrospective monoinstitutional assessment of CA125-related versus Gynecologic
      Cancer Inter Group-related parameters was performed after cytotoxic chemotherapy
      in patients with metastatic ovarian cancer treated from 2006 to 2011. A
      correlation analysis between the response and progression measurements has been
      performed, and the outcome has been reported. RESULTS: Among 42 eligible
      patients, tumor response and progression calculated by CA125 kinetics, with tumor
      response at 8 weeks and specific growth rate at progression, exhibited a
      significant correlation with progression-free and overall survival, similar to
      tumor response and progression by Gynecologic Cancer Inter Group criteria.
      CONCLUSIONS: The tumor response at 8 weeks higher than 1.77 appears to be a good
      surrogate of clinical response, whereas the definition of progression when CA125
      increases above a value double than the nadir suggests a similar performance of
      growth rate at progression versus Gynecologic Cancer Inter Group criteria and
      warrants further investigation.

PMID- 24038195
TI  - Fluorinated graphene oxide; a new multimodal material for biological
      applications.
AB  - Fluorinated graphene oxide (FGO) is reported for the first time as a magnetically
      responsive drug carrier that can serve both as a magnetic resonance imaging (MRI)
      and photoacoustic contrast agent, under preclinical settings, and as a type of
      photothermal therapy. Its hydrophilic nature facilitates biocompatibility. FGO as
      a broad wavelength absorber, with high charge transfer and strong non-linear
      scattering is optimal for NIR laser-induced hyperthermia. 

PMID- 24038196
TI  - Exploring the feasibility of text messaging to support substance abuse recovery
      among youth in treatment.
AB  - This exploratory study examined treatment involved youth opinions about (i) the
      utility of using text messaging to support recovery behaviors after treatment;
      (ii) important types of text messages that could help youth self-manage their
      substance use behaviors after treatment; and (iii) programmatic or logistical
      areas associated with text messaging programs. Eight focus groups were conducted
      with 67 youth (aged 12-24) enrolled in outpatient and residential publicly funded
      substance abuse treatment programs around Los Angeles County, California. Results
      highlight that 70% of youth positively endorsed text messaging as a viable method
      of intervention during aftercare, 20% expressed ambivalent feelings, and 10%
      conveyed dislike. Thematic data exploration revealed seven themes related to the
      types of text messages youth recommend for helping youth avoid relapse after
      treatment, including positive appraisal (90%), lifestyle change tips (85%),
      motivational reinforcing (80%), coping advice (75%), confidence boosters (65%),
      inspiration encouragement (55%), and informational resources (50%). Youth
      opinions about key logistical features of text messaging programs, including
      frequency, timing, sender, and length are also examined. Findings offer insight
      for the development and enhancement of recovery support interventions with
      substance abusing youth. Results imply text messaging may serve as a promising
      opportunity for recovery support for young people with substance abuse problems. 

PMID- 24038197
TI  - Midtarsal joint locking: new perspectives on an old paradigm.
AB  - We investigated the existence of a midtarsal joint locking mechanism using
      cadaveric simulations of normal gait. Previous descriptions of this phenomenon
      led us to hypothesize that non-coupled rotations of the calcaneocuboid and
      talonavicular (i.e., midtarsal) joints and cubonavicular and talocalcaneal joints
      occur at heel strike and during weight acceptance, after which joint rotations
      cease with all bone-to-bone orientations remaining constant during the latter
      portions of stance phase. Three-dimensional kinematics of the talus, calcaneus,
      cuboid, and navicular were recorded along with muscle and ground reaction forces.
      Finite helical axis parameters and joint angles of directly articulating bones
      were subsequently derived and examined. During weight acceptance, the midtarsal
      joints everted with obvious changes in the relative orientation of their helical
      axes. The relative non-parallel orientation of these axes then remained constant
      until late in stance when these joints inverted and dorsiflexed toward their
      original pre-stance orientation. The cubonavicular and talocalcaneal joints
      demonstrated complimentary behavior. Contrary to our hypothesis, the midtarsal
      joints remained compliant during foot flat and even more so during push-off,
      despite divergent joint axes. Joint rotations were present after weight
      acceptance, thereby challenging the concept that midtarsal joint locking produces
      a rigid lever during push-off. (c) 2013 Orthopaedic Research Society. Published
      by Wiley Periodicals, Inc. J Orthop Res 32:110-115, 2014. 

PMID- 24038198
TI  - Dual pH- and temperature-responsive metallosupramolecular block copolymers with
      tunable critical micelle temperature by modulation of the self-assembly of NIR
      emissive alkynylplatinum(II) Complexes induced by changes in hydrophilicity and
      electrostatic effects.
AB  - Terpyridylplatinum(II)-based metallosupramolecular triblock copolymers with
      hydrophilic alkynyl ligands have been synthesised and characterised. As a result
      of the intrinsic properties of Pluronics, reversible temperature-induced
      micellisation occurred at high temperature leading to aggregation of the
      platinum(II) complex moieties through Pt???Pt and pi-pi interactions, resulting
      in significant UV/Vis absorption and near-infrared (NIR) emission spectral
      changes. The critical micelle temperatures of the complexes were found to vary
      from 21 to 30  degrees C due to differences in the hydrophilicity of the alkynyl
      ligands and the electrostatic repulsions between the positively charged
      platinum(II) complex moieties. One of the complexes with pH-responsive CH2NMe2
      groups on the alkynyl ligand was found to show NIR emission that is sensitive to
      both pH and temperature. Such dual-responsive behaviour has been ascribed to the
      modulation of the self-assembly of the complex moieties by temperature-induced
      micellisation and the changes in the hydrophilicity as well as electrostatic
      interactions upon protonation/deprotonation of the CH2NMe2 groups on the alkynyl
      ligand.

PMID- 24038199
TI  - Comparison of the morphology of the rotator cuff muscles across age groups.
AB  - We aimed at investigating the morphological difference of the rotator cuff (RC)
      muscles among age groups from elementary school students to college students. The
      subjects included 10 college (22.6 +/- 1.8 years), 10 high school (16.8 +/- 0.6
      years), 10 junior high school (13.9 +/- 0.6 years), and 10 elementary school
      (10.4 +/- 0.5 years) students. Consecutive oblique sagittal magnetic resonance T1
      -weighted images of the dominant shoulder were acquired for each participant.
      Muscle length, maximal anatomical cross-sectional area (ACSA), the position of
      the maximal ACSA at full muscle length, muscle volume, and the individual-to
      total RC muscle volume ratio for the supraspinatus, external rotators
      (infraspinatus and teres minor), and subscapularis were evaluated. The muscle
      length, maximal ACSA, and muscle volume in the RC muscles significantly increased
      with increasing age (P < 0.01), but there was no significant difference between
      college and high school students except in regard to the volume of the external
      rotators. There was no difference in the position of the maximal ACSA or the
      individual-to-total RC muscle volume ratio among the groups. The findings of this
      study show that the size of each RC muscle increases with increasing age, but the
      position of maximal ACSA and the proportion of each muscle to the total RC muscle
      volume are similar among age groups from elementary school students to college
      students.

PMID- 24038200
TI  - The utility of PSA velocity in prediction of prostate cancer and high grade
      cancer after an initially negative prostate biopsy.
AB  - BACKGROUND: Prostate specific antigen kinetics (PSAK) including prostate specific
      antigen velocity (PSAV) and PSA doubling time (PSADT) are used as predictors of
      prostate cancer (PCa) therapeutic outcome, disease prognosis, and cancer-specific
      mortality. However controversy persists regarding use of these parameters in
      cancer detection. Our aim is to evaluate PSAV as a predictor of PCa and
      intermediate/high grade PCa (HGPCa). METHODS: We included 682 patients that
      underwent repeat transrectal ultrasound guided biopsy after initial negative
      biopsy. Univariate and multivariate analyses as well as area under the receiver
      operating characteristic curve (ROC-AUC) were performed to assess predictive
      accuracy regarding detection of PCa and intermediate/HGPCa (Gleason score >= 7).
      RESULTS: PCa was detected in 179/682 (26.24%) patients. Our univariate analysis
      suggested that age, total prostate volume (TPV), atypical small acinar
      proliferation (ASAP) and PSA indices in the form of PSA at the time of repeat
      biopsy (PSA2), PSAV, PSA density (PSAD2) and percent free PSA at time of repeat
      biopsy (%FPSA2) were all predictors of overall PCa and intermediate/HGPCa.
      Meanwhile, our multivariate model showed that factors associated with overall PCa
      and intermediate/HGPCa were age, PSAV and TPV. CONCLUSIONS: In men pursuing a
      second biopsy after an initial negative biopsy, PSAV was an independent predictor
      of overall PCa, intermediate and high grade cancer.

PMID- 24038201
TI  - miR-34c enhances mouse spermatogonial stem cells differentiation by targeting
      Nanos2.
AB  - miRNAs are expressed in many mammalian cells, acting specific roles in regulating
      gene expression or mediating special mRNAs cleavage by targeting their 3'
      untranslated region (3'UTR). Some miRNAs are essential and important for animal
      development. However, it is still unclear what the relationship is between miR
      34c and mammalian spermatogonial stem cells (SSCs). We found that a conserved
      microRNA-34c through its target-Nanos2, regulating SSCs' differentiation in
      mouse. Immunohistochemistry analysis of Nanos2 and miR-34c FISH results revealed
      the opposite expression trends between them. Seven bioinformatics websites and
      programs predicted that miR-34c has interaction sites in Nanos2's 3'UTR. Dual
      luciferase reporter vector and mutated dual-luciferase reporter vector analysis
      validated that they are interacted. After transfection miR-34c mimics into mouse
      SSCs, or miR-34c lentiviral vector in vitro co-cultivation with seminiferous
      tubules, and Western blot analysis demonstrated that miR-34c over-expression
      could suppress Nanos2 expression in post-transcription level. Our experiments
      identified that miR-34c may promote meiosis process by interacting with Nanos2
      leading up-regulation of Stra8 in mouse spermatogonial stem cells.

PMID- 24038202
TI  - Allocation of cysteine for glutathione production in caterpillars with different
      antioxidant defense strategies: a comparison of Lymantria dispar and Malacosoma
      disstria.
AB  - Sulfur amino acids [cysteine (Cys) and methionine (Met)] play two major roles
      during animal development: protein synthesis for growth and glutathione synthesis
      for defense. For caterpillars, the levels of sulfur amino acids found in foliar
      protein can be especially low relative to their nutritional needs. Previous work
      has measured concentrations of glutathione (GSH; containing Cys) in specific
      animal tissues, but has not examined whole-body levels to ascertain the
      costliness of this defense in terms of Cys allocation. This study examined
      whether the production of GSH varies between species and within individuals in
      accordance with an insect's need for antioxidant defense. Secondly, we quantified
      the allocation of total Cys (peptide-bound plus free Cys) to GSH in caterpillars
      as an estimate of its cost. Two contrasting species were compared: Lymantria
      dispar (Lymantriidae), a species that is highly defended, and Malacosoma disstria
      (Lasiocampidae), a species that is less defended. As expected, GSH levels were
      significantly higher in L. dispar than in M. disstria. Consistent with the
      function of the midgut as a first line of defense against ingested toxins, GSH
      levels were significantly higher in these tissues than in the whole bodies of
      both species. A major finding in this study was that a large fraction of total
      Cys is used to produce GSH: GSH in the midguts of L. dispar and M. disstria
      contained 23 and 21%, respectively, of the total Cys in these tissues, and the
      GSH in their remaining body tissues contained 19 and 17% of the total Cys in
      these tissues. Levels of total Cys in caterpillar tissues followed the same
      pattern of distribution as did GSH, producing a strong association between GSH
      and total Cys (R(2) = 0.794). We conclude that GSH is a costly defense,
      especially in generalist tree-feeding species such as L. dispar. These results
      further suggest that the large allocation of Cys to GSH in highly defended
      species might produce a tradeoff by limiting the amount of Cys available for
      rapid growth. 

PMID- 24038203
TI  - Comparative evaluation of brain neurometabolites and DTI indices following whole
      body and cranial irradiation: a magnetic resonance imaging and spectroscopy
      study.
AB  - Understanding early differential response of brain during whole body radiation or
      cranial radiation exposure is of significant importance for better injury
      management during accidental or intentional exposure to ionizing radiation. We
      investigated the early microstructural and metabolic profiles using in vivo
      diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H
      MRS) following whole body and cranial radiation exposure of 8 Gy in mice using a
      7.0 T animal MRI system and compared profiles with sham controls at days 1, 3, 5
      and 10 post irradiation. A significant decrease in fractional anisotropy (FA)
      values was found in hippocampus, thalamic and hypothalamic regions (p < 0.05) in
      both whole body and cranial irradiated groups compared with controls, suggesting
      radiation induced reactive astrogliosis or neuroinflammatory response. In animals
      exposed to whole body radiation, FA was significantly decreased in some
      additional brain regions such as sensory motor cortex and corpus callosum in
      comparison with cranial irradiation groups and controls. Changes in FA were
      observed till day 10 post irradiation in both the groups. However, MRS study from
      hippocampus revealed changes only in the whole body radiation dose group.
      Significant reduction in the ratios of the metabolites myoinositol (mI, p = 0.02)
      and taurine (tau, p = 0.03) to total creatine were observed, and these metabolic
      alterations persisted till day 10 post irradiation. To the best of our knowledge
      this study has for the first time documented a comparative account of
      microstructural and metabolic aspects of whole body and cranial radiation induced
      early brain injury using in vivo MRI. Overall our findings suggest differential
      response at microstructure and metabolite levels following cranial or whole body
      radiation exposure.

PMID- 24038204
TI  - Sample size calculation for comparing two negative binomial rates.
AB  - Negative binomial model has been increasingly used to model the count data in
      recent clinical trials. It is frequently chosen over Poisson model in cases of
      overdispersed count data that are commonly seen in clinical trials. One of the
      challenges of applying negative binomial model in clinical trial design is the
      sample size estimation. In practice, simulation methods have been frequently used
      for sample size estimation. In this paper, an explicit formula is developed to
      calculate sample size based on the negative binomial model. Depending on
      different approaches to estimate the variance under null hypothesis, three
      variations of the sample size formula are proposed and discussed. Important
      characteristics of the formula include its accuracy and its ability to explicitly
      incorporate dispersion parameter and exposure time. The performance of the
      formula with each variation is assessed using simulations.

PMID- 24038205
TI  - Workplace injustice and self-reported disease and absenteeism in South Korea.
AB  - BACKGROUND: This study investigated whether experience of workplace injustice was
      associated with self-reported occupational health using a nationally
      representative sample of Korean workers. METHODS: We used the first wave of the
      Korean Working Conditions Survey (KWCS) and included 7,007 wage employees as the
      study population. Workplace injustice included the experience of discrimination,
      violence, or harassment, and occupational health was measured as self-reported
      health problems and absenteeism. Personal, occupational, and job-related
      characteristics were included as covariates. RESULTS: An average of 7.2% of
      workers reported experiencing at least one workplace injustice over the past 12
      months. Female workers were significantly more likely to experience age and
      gender discrimination, and unwanted sexual attention than male workers. Both male
      and female workers who experienced any workplace injustice (i.e., discrimination,
      harassment, or violence) reported approximately two- to threefold increased risk
      for physical and mental health problems (i.e., backaches, muscular pain, stomach
      pain, overall fatigue, headaches, anxiety/depression, sleeping problems, and
      injury) and absenteeism due to accidents or due to health problems. CONCLUSION:
      Perceived injustice at work was significantly associated with an increased risk
      of occupational disease and absenteeism for Korean wage employees.

PMID- 24038206
TI  - Carcinogenic organic residual compounds readsorbed on thermally reduced graphene
      materials are released at low temperature.
AB  - The preliminary oxidation of graphite to graphite oxide followed by a thermal
      exfoliation is one of the methods most frequently employed in the preparation of
      graphene. Such thermally reduced graphene can be widely used for several
      applications that range from coatings to sensing device fabrication. It is
      therefore important to investigate in detail the fabrication procedure, the
      structural features of the resulting graphene, and its potential toxicological
      effects. Low-molecular-weight and carcinogenic compounds are known to be
      generated during the thermal reduction/exfoliation of graphite oxide. Such
      compounds are readsorbed onto the reduced material during the cooling process. We
      investigate here the composition of the organic compounds that are adsorbed onto
      the graphene material and show that they can be easily released during the
      following processing steps even at temperatures as low as 50  degrees C. Some of
      the released organic compounds are classified as highly carcinogenic. The results
      shown here are important not only from a chemical point of view to better
      understand the composition and properties of the graphene material produced, but
      also to bring attention to the potential toxicological effects that the synthesis
      itself or the post-production processes can cause. 

PMID- 24038207
TI  - Highly efficient C-H oxidative activation by a porous Mn(III) -porphyrin metal
      organic framework under mild conditions.
AB  - A simple strategy to rationally immobilize metalloporphyrin sites into porous
      mixed-metal-organic framework (M'MOF) materials by a metalloligand approach has
      been developed to mimic cytochrome P450 monooxygenases in a biological system.
      The synthesized porous M'MOF of [Zn2 (MnOH-TCPP)(DPNI)]?0.5 DMF?EtOH?5.5 H2 O
      (CZJ-1; CZJ=Chemistry Department of Zhejiang University; TCPP=tetrakis(4
      carboxyphenyl)porphyrin); DPNI=N,N'-di(4-pyridyl)-1,4,5,8
      naphthalenetetracarboxydiimide) has the type of doubly interpenetrated cubic
      alpha-Po topology in which the basic Zn2 (COO)4 paddle-wheel clusters are bridged
      by metalloporphyrin to form two-dimensional sheets that are further bridged by
      the organic pillar linker DPNI to form a three-dimensional porous structure. The
      porosity of CZJ-1 has been established by both crystallographic studies and gas
      sorption isotherms. CZJ-1 exhibits significantly high catalytic oxidation of
      cyclohexane with conversion of 94 % to the mixture of cyclohexanone (K) and
      cyclohexanol (A) (so-called K-A oil) at room temperature. We also provided solid
      experimental evidence to verify the catalytic reaction that occurred in the pores
      of the M'MOF catalyst. 

PMID- 24038208
TI  - Spatial working memory in immersive virtual reality foraging: path organization,
      traveling distance and search efficiency in humans (Homo sapiens).
AB  - Search and serial recall tasks were used in the present study to characterize the
      factors affecting the ability of humans to keep track of a set of spatial
      locations while traveling in an immersive virtual reality foraging environment.
      The first experiment required the exhaustive exploration of a set of locations
      following a procedure previously used with other primate and non-primate species
      to assess their sensitivity to the geometric arrangement of foraging sites. The
      second experiment assessed the dependency of search performance on search
      organization by requiring the participants to recall specific trajectories
      throughout the foraging space. In the third experiment, the distance between the
      foraging sites was manipulated in order to contrast the effects of organization
      and traveling distance on recall accuracy. The results show that humans benefit
      from the use of organized search patterns when attempting to monitor their travel
      though either a clustered "patchy" space or a matrix of locations. Their ability
      to recall a series of locations is dependent on whether the order in which they
      are explored conformed or did not conform to specific organization principles.
      Moreover, the relationship between search efficiency and search organization is
      not confounded by effects of traveling distance. These results indicate that in
      humans, organizational factors may play a large role in their ability to forage
      efficiently. The extent to which such dependency may pertain to other primates
      and could be accounted for by visual organization processes is discussed on the
      basis of previous studies focused on perceptual grouping, search, and serial
      recall in non-human species.

PMID- 24038209
TI  - Female mice lacking estrogen receptor-alpha in osteoblasts have compromised bone
      mass and strength.
AB  - Reduced bioavailability of estrogen increases skeletal fracture risk in
      postmenopausal women, but the mechanisms by which estrogen regulates bone mass
      are incompletely understood. Because estrogen signaling in bone acts, in part,
      through estrogen receptor alpha (ERalpha), mice with global deletion of ERalpha
      (ERalphaKO) have been used to determine the role of estrogen signaling in bone
      biology. These animals, however, have confounding systemic effects arising from
      other organs, such as increased estrogen and decreased insulin-like growth factor
      1 (IGF-1) serum levels, which may independently affect bone. Mice with tissue
      specific ERalpha deletion in chondrocytes, osteoblasts, osteocytes, or
      osteoclasts lack the systemic effects seen in the global knockout, but show that
      presence of the receptor is important for the function of each cell type.
      Although bone mass is reduced when ERalpha is deleted from osteoblasts, no study
      has determined if this approach reduces whole bone strength. To address this
      issue, we generated female osteoblast-specific ERalphaKO mice (pOC-ERalphaKO) by
      crossing mice expressing a floxed ERalpha gene (ERalpha(fl/fl)) with mice
      transgenic for the osteocalcin-Cre promoter (OC-Cre). Having confirmed that serum
      levels of estrogen and IGF-1 were unaltered, we focused on relating bone
      mechanics to skeletal phenotype using whole bone mechanical testing,
      microcomputed tomography, histology, and dynamic histomorphometry. At 12 and 18
      weeks of age, pOC-ERalphaKO mice had decreased cancellous bone mass in the
      proximal tibia, vertebra, and distal femur, and decreased cortical bone mass in
      the tibial midshaft, distal femoral cortex, and L5 vertebral cortex. Osteoblast
      activity was reduced in cancellous bone of the proximal tibia, but osteoclast
      number was unaffected. Both femora and vertebrae had decreased whole bone
      strength in mechanical tests to failure, indicating that ERalpha in osteoblasts
      is required for appropriate bone mass and strength accrual in female mice. This
      pOC-ERalphaKO mouse is an important animal model that could enhance our
      understanding of estrogen signaling in bone cells in vivo.

PMID- 24038211
TI  - Bioinspired conical copper wire with gradient wettability for continuous and
      efficient fog collection.
AB  - Inspired by the efficient fog collection on cactus spines, conical copper wires
      with gradient wettability are fabricated through gradient electrochemical
      corrosion and subsequent gradient chemical modification. These dual-gradient
      copper wires' fog-collection ability is demonstrated to be higher than that of
      conical copper wires with pure hydrophobic surfaces or pure hydrophilic surfaces,
      and the underlying mechanism is also analyzed. 

PMID- 24038210
TI  - New innovations: therapeutic opportunities for intellectual disabilities.
AB  - Intellectual disability is common and is associated with significant morbidity.
      Until the latter half of the 20th century, there were no efficacious treatments.
      Following initial breakthroughs associated with newborn screening and metabolic
      corrections, little progress was made until recently. With improved understanding
      of genetic and cellular mechanisms, novel treatment options are beginning to
      appear for a number of specific conditions. Fragile X and tuberous sclerosis
      offer paradigms for the development of targeted therapeutics, but advances in
      understanding of other disorders such as Down syndrome and Rett syndrome, for
      example, are also resulting in promising treatment directions. In addition,
      better understanding of the underlying neurobiology is leading to novel
      developments in enzyme replacement for storage disorders and adjunctive therapies
      for metabolic disorders, as well as potentially more generalizable approaches
      that target dysfunctional cell regulation via RNA and chromatin. Physiologic
      therapies, including deep brain stimulation and transcranial magnetic
      stimulation, offer yet another direction to enhance cognitive functioning.
      Current options and evolving opportunities for the intellectually disabled are
      reviewed and exemplified.

PMID- 24038212
TI  - Highly stable duplex formation by artificial nucleic acids acyclic threoninol
      nucleic acid (aTNA) and serinol nucleic acid (SNA) with acyclic scaffolds.
AB  - The stabilities of duplexes formed by strands of novel artificial nucleic acids
      composed of acyclic threoninol nucleic acid (aTNA) and serinol nucleic acid (SNA)
      building blocks were compared with duplexes formed by the acyclic glycol nucleic
      acid (GNA), peptide nucleic acid (PNA), and native DNA and RNA. All acyclic
      nucleic acid homoduplexes examined in this study had significantly higher thermal
      stability than DNA and RNA duplexes. Melting temperatures of homoduplexes were in
      the order of aTNA>PNA~GNA>=SNA?RNA>DNA. Thermodynamic analyses revealed that high
      stabilities of duplexes formed by aTNA and SNA were due to large enthalpy changes
      upon formation of duplexes compared with DNA and RNA duplexes. The higher
      stability of the aTNA homoduplex than the SNA duplex was attributed to the less
      flexible backbone due to the methyl group of D-threoninol on aTNA, which induced
      clockwise winding. Unlike aTNA, the more flexible SNA was able to cross-hybridize
      with RNA and DNA. Similarly, the SNA/PNA heteroduplex was more stable than the
      aTNA/PNA duplex. A 15-mer SNA/RNA was more stable than an RNA/DNA duplex of the
      same sequence. 

PMID- 24038214
TI  - A new family of two-dimensional zeolites prepared from the intermediate layered
      precursor IPC-3P obtained during the synthesis of TUN zeolite.
AB  - The crystallization of zeolite TUN with 1,4-bis(N-methylpyrrolidinium)butane as
      template proceeds through an intermediate, designated IPC-3P, following the
      Ostwald rule of successive transformations. This apparently layered transient
      product has been thoroughly investigated and found to consist of MWW monolayers
      stacked without alignment in register, that is, disordered compared with MCM-22P.
      The structure was confirmed based on X-ray diffraction and high-resolution
      (HR)TEM analysis. The layered zeolite precursor IPC-3P can be swollen and
      pillared affording a combined micro- and mesoporous material with enhanced
      Brunauer-Emmett-Teller (BET) surface area (685 m(2) g(-1) ) and greater
      accessibility of Bronsted acid sites for bulky molecules. This mesoporous
      material was probed with 2,6-di-tert-butylpyridine (DTBP). IPC-3P and its
      modification create a new layered zeolite sub-family belonging to the MWW family.
      FTIR data indicate that (Al)MWW materials MCM-22 and IPC-3 with Si/Al ratios
      greater than 20 exhibit a lower relative ratio of Bronsted to Lewis acid sites
      than MCM-22 (with Si/Al ratios of around 13), that is, less than 2 versus more
      than 3, respectively. This is maintained even upon pillaring and warrants further
      exploration of materials like IPC-3P with a higher Al content. The unique XRD
      features of IPC-3P indicating misaligned stacking of layers and distinct from MCM
      22P, are also seen in other MWW materials such as EMM-10P, hexamethonium
      templated (HM)-MCM-22, ITQ-30, and UZM-8 suggesting the need for more detailed
      study of their identity and properties. 

PMID- 24038213
TI  - Tolterodine activates the prefrontal cortex during bladder filling in OAB
      patients: a real-time NIRS-urodynamics study.
AB  - AIMS: Studies of overactive bladder (OAB) have shown urothelial/suburothelial
      changes and increased bladder afferents, while in the brain the frontal
      micturition area that normally suppresses the bladder is deactivated. It has been
      unclear whether anticholinergic medication could reverse this suppression. To
      address this question, we performed a real-time NIRS (near-infrared spectroscopy)
      urodynamic study in OAB patients before and after the administration of an
      anticholinergic agent, tolterodine. METHODS: We recruited 13 OAB patients in our
      outpatient clinic (9 males, 4 female; mean age 73 years). Before and after the
      administration of 4 mg/day tolterodine for 3 months, all patients completed the
      OAB-symptom scale and a NIRS-urodynamics examination. Cerebral changes in the oxy
      hemoglobin concentration (oxy-Hb) were sampled. Concentration changes in oxy-Hb
      were calculated based on a modified Beer-Lambert approach. RESULTS: Tolterodine
      significantly reduced the OAB patients' nighttime frequency (P < 0.05) and
      increased their first-sensation volume (290-359 ml, P < 0.01). The number of
      patients with detrusor overactivity did not lessen significantly (11-9). The real
      time NIRS-urodynamic study showed that, during slow bladder filling between start
      and bladder capacity, tolterodine significantly activated the right frontal
      micturition area of the OAB patients (P < 0.05). The activation was prominent in
      Brodmann's area 8, 9, 10 of the prefrontal cortex. CONCLUSIONS: Tolterodine
      reduced bladder sensation together with a significant activation of the frontal
      micturition area of OAB patients, particularly Brodmann's area 8, 9, 10 of the
      right prefrontal cortex. This activation seems to be a secondary phenomenon,
      since tolterodine does not easily penetrate the blood-brain barrier.

PMID- 24038215
TI  - Inhibition of apolipoprotein A-I expression by TNF-alpha in HepG2 cells:
      requirement for c-jun.
AB  - Tumor necrosis factor alpha (TNF alpha) signals in part through the mitogen
      activated protein (MAP) kinase c-jun-N-terminal kinase (JNK). Activation of JNK
      has been shown to promote insulin resistance and dyslipidemia, including
      reductions in plasma high-density lipoprotein (HDL) and apolipoprotein A-I (apo A
      I). To examine how TNF alpha-mediated JNK activation inhibits hepatic apo A-I
      production, the effects of c-jun activation on apo A-I gene expression were
      examined in HepG2 cells. Apo A-I gene expression and promoter activity were
      measured by Northern and Western blotting and transient transfection. Transient
      transfection and siRNA were used to specifically over-express or knockout c-jun,
      c-jun-N-terminal kinase-1 and -2 (JNK1 and JNK2, respectively) and mitogen
      activated protein kinase-4 (MKK4). TNF alpha-treatment of HepG2 cells induced
      rapid phosphorylation of c-jun on serine 63. In cells treated with phorbol-12
      myristate-13-acetate (PMA), apo A-I gene promoter activity was inhibited and apo
      A-I mRNA content and apo A-I protein secretion decreased. Likewise, over
      expression of JNK1 and JNK2 inhibited apo A-I promoter activity. Over-expression
      of constitutively active MKK4, an upstream protein kinase that directly activates
      JNK, also inhibited apo A-I promoter activity, while over-expression of a
      dominant-negative MKK4 de-repressed apo A-I promoter activity in TNF alpha
      treated cells. Inhibition of c-jun synthesis using siRNA but not a control siRNA
      prevented TNF alpha-mediated inhibition of apo A-I. These results suggest that
      the MKK4/JNK/c-jun signaling pathway mediates TNF alpha-dependent inhibition of
      apo A-I synthesis.

PMID- 24038217
TI  - Prostate MR: current status, challenges and future directions.

PMID- 24038216
TI  - The tumor suppressor gene DAPK2 is induced by the myeloid transcription factors
      PU.1 and C/EBPalpha during granulocytic differentiation but repressed by PML
      RARalpha in APL.
AB  - DAPK2 is a proapoptotic protein that is mostly expressed in the hematopoietic
      tissue. A detailed DAPK2 expression analysis in two large AML patient cohorts
      revealed particularly low DAPK2 mRNA levels in APL. DAPK2 levels were restored in
      APL patients undergoing ATRA therapy. PML-RARA is the predominant lesion in APL
      causing transcriptional repression of genes important for neutrophil
      differentiation. We found binding of PML-RARA and PU.1, a myeloid master
      regulator, to RARA and PU.1 binding sites in the DAPK2 promoter. Ectopic
      expression of PML-RARA in non-APL, as well as knocking down PU.1 in APL cells,
      resulted in a significant reduction of DAPK2 expression. Restoring DAPK2
      expression in PU.1 knockdown APL cells partially rescued neutrophil
      differentiation, thereby identifying DAPK2 as a relevant PU.1 downstream
      effector. Moreover, low DAPK2 expression is also associated with C/EBPalpha
      mutated AML patients, and we found C/EBPalpha-dependent regulation of DAPK2
      during APL differentiation. In conclusion, we identified first inhibitory
      mechanisms responsible for the low DAPK2 expression in particular AML subtypes,
      and the regulation of DAPK2 by two myeloid transcription factors underlines its
      importance in neutrophil development. 

PMID- 24038218
TI  - A simple, fast correction method of triglyceride interference in blood hemoglobin
      automated measurement.
AB  - BACKGROUND: To establish a reliable correction method for automated hemoglobin
      (HGB) measurement by minimizing the interference from blood high triglyceride
      (TG). METHODS: Fifty whole blood samples and 50 plasma samples containing
      variable TG concentrations were used to determine the centrifugation speed and
      time. Complete blood cell counts (CBCs) were performed by an automated hematology
      analyzer for 102 blood samples, in which high-level TG were artificially added.
      The same blood samples were centrifuged at low -speed to separate the plasma from
      blood cells. Then the plasma was analyzed by the same analyzer. By using the two
      CBC results, a correction formula was established to calculate the corrected HGB,
      mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration
      (MCHC) values. Comparisons were also made of HGB, MCH, and MCHC values before and
      after correction of in-patient individuals who received intralipid and developed
      lipemia. RESULTS: The percentage differences between the corrected and true
      values of HGB, MCH and MCHC were -0.28%, 0.06%, and -0.31%, respectively. The
      correlation coefficients of corrected values versus true values of HGB, MCH, and
      MCHC were 0.989, 0.935, and 0.717, respectively. This correction method was also
      effective for native lipemic samples. CONCLUSION: High blood TG level can cause
      blood turbidity and erroneously high HGB results by hematology analyzers commonly
      used in clinical laboratories. Adding a simple step of low-speed centrifugation
      and measurement of HGB in the plasma fraction allows a quick correction of HGB
      measurement in lipemic blood samples.

PMID- 24038219
TI  - Trends in prevalence of HIV-1 drug resistance in Thailand 2009-2010.
AB  - BACKGROUND: Treatment failure of antiretroviral therapy in HIV-1 infection is
      increasing due to development of viral resistance. Trends of resistance
      associated mutation lead to the ineffective treatment in HIV-infected
      individuals. METHODS: Extracted viral RNA from HIV-infected subjects in 2009 to
      2010 was performed. The genotypic resistance testing was investigated for HIV-1
      drug resistance in RT and PR genes. Frequencies of mutation were compared by a
      Fischer's exact test. RESULTS: Three hundred and sixty-nine samples (147 in 2009
      and 222 in 2010) were genotyped. At least one mutation was found in 90.8%
      (335/369) in PR gene and 87.0% (321/369) in RT gene. Three sequences in PR gene,
      M36I, H69K, and L90M, were decreased significantly in 2010 when compared to 2009.
      Mutations associated with resistance to nucleoside analogue reverse transcriptase
      inhibitors (NRTI's) were found in 61.0% and 64.2% in nonnucleoside analogue
      reverse transcriptase inhibitors (NNRTI's). A total of 49.6% was found in
      combined NRTI and NNRTI. In 2010, M41L was increased significantly from 7.5% to
      14.9%. However, there was a decrease in the frequency of the mutations at
      position 67, 70, and 184 between 2009 and 2010. CONCLUSIONS: In 2010, three
      mutations in PR gene, M36I, H69K, and L90M, were decreased significantly.
      However, only one mutation in RT gene, M41L was significantly increased.

PMID- 24038220
TI  - Factors interfering with the accuracy of five blood glucose meters used in
      Chinese hospitals.
AB  - BACKGROUND: The prevalence of diabetes is increasing in China. Glucose control is
      very important in diabetic patients. The aim of this study was to compare the
      accuracy of five glucose meters used in Chinese hospitals with a reference
      method, in the absence and presence of various factors that may interfere with
      the meters. METHODS: Within-run precision of the meters was evaluated include
      Roche Accu-Chek Inform(r), Abbott Precision PCx FreeStyle(r), Bayer Contour(r),
      J&J LifeScan SureStep Flexx(r), and Nova Biomedical StatStrip(r). The
      interference of hematocrit level, maltose, ascorbic acid, acetaminophen,
      galactose, dopamine, and uric acid were tested in three levels of blood glucose,
      namely low, medium, and high concentrations. Accuracy (bias) of the meters and
      analytical interference by various factors were evaluated by comparing results
      obtained in whole blood specimens with those in plasma samples of the whole blood
      specimens run on the reference method. Impact of oxygen tension on above five
      blood glucose meters was detected. RESULTS: Precision was acceptable and slightly
      different between meters. There were no significant differences in the
      measurements between the meters and the reference method. The hematocrit level
      significantly interfered with all meters, except StatStrip. Measurements were
      affected to varying degrees by different substances at different glucose levels,
      e.g. acetaminophen and ascorbic acid (Freestyle), maltose and galactose
      (FreeStyle, Accu-Chek), uric acid (FreeStyle, Bayer Contour), and dopamine (Bayer
      Contour). CONCLUSIONS: The measurements with the five meters showed a good
      correlation with the plasma hexokinase reference method, but most were affected
      by the hematocrit level. Some meters also showed marked interference by other
      substances.

PMID- 24038221
TI  - Evaluation of Ves-Matic Cube 200 for erythrocyte sedimentation rate
      determination.
AB  - BACKGROUND: International Council for Standardization in Haematology suggested
      Westergren method as the reference method to analyze erythrocyte sedimentation
      rate (ESR). However, in recent years closed automated systems that measure ESR
      directly from a capped EDTA blood sample tube have been developed. We evaluated
      the analytic performance of one of these new methods, the Ves-Matic Cube 200.
      METHODS: K(2) EDTA and citrated blood samples were taken from 101 randomly
      selected outpatients in Ankara Numune Education and Research Hospital. The ESR
      results using Ves-Matic Cube 200 and Westergren as reference method from 101
      patients were compared and interference studies were performed. RESULTS: We found
      the mean difference between the two methods as 0.19 +/- 15.85 mm/hr (-3.317 to
      2.940 mm/hr, 95% confidence interval). Regression analysis yielded the equation
      "y = -2.59 + 1.15x" between the two methods (r = 0.82). CONCLUSIONS: Ves-Matic
      Cube 200 should be monitored carefully for good quality control. Temperature
      correction should be applied to study control material as recommended by the
      manufacturer. Ves-Matic Cube 200 device should be monitored carefully,
      performance studies should be performed, and the results should be checked in
      order to eliminate the random errors during the routine studies.

PMID- 24038222
TI  - Mean corpuscular volume (MCV) values reflect therapeutic effectiveness in
      zidovudine-receiving HIV patients.
AB  - BACKGROUND: An increase of the mean corpuscular volume (MCV) of erythrocytes and
      alterations in the lipid profiles have been described in HIV-infected patients
      under combination of anti-retroviral treatment (cART), particularly zidovudine
      (AZT). METHODS: In 687 sera from 179 HIV-positive patients, MCV levels were
      correlated with the clinical outcome or therapeutic effectiveness. The sera were
      classified into three groups according to AZT treatment; cART with AZT (n = 317),
      cART without AZT (n = 262), and no anti-retroviral therapy (n = 108). RESULTS:
      The MCV and lipid profile values were increased after cART. The AZT-based cART
      group had higher MCV levels (111.6 +/- 7.0 vs. 97.8 +/- 7.0 fl, P < 0.001) and a
      higher incidence of macrocytosis (>99 fl; 95.3% vs. 38.2%, P < 0.001) than the
      non-AZT-based cART group. The receiver operating characteristic curve analysis
      showed that the area under the curve was 0.835 and the cut-off of MCV (>102 fl)
      had a sensitivity of 96.1% and specificity of 66.7% for detecting HIV-RNA (-)
      sera in AZT-based cART group. In the multivariate regression analysis, HIV-viral
      load and HDL-cholesterol were the only significant correlates to the MCV values
      in the AZT-base cART group (P < 0.05). CONCLUSION: The MCV values could be used
      as a surrogate marker to monitor the clinical outcome of HIV-infected patients
      receiving AZT-based cART.

PMID- 24038223
TI  - Can we predict postoperative pancreatic leakage after pancreaticoduodenectomy
      using preoperative fecal elastase-1 level?
AB  - INTRODUCTION: The measurement of fecal elastas-1 in stools is a sensitive and
      relatively inexpensive noninvasive test. The aim of this study was to study fecal
      elastase levels in patients who develop pancreatic leakage after
      pancreaticoduodenectomy (PD) to determine if fecal elastase level can be used to
      predict patients at high risk for pancreatic leakage after PD. METHODS:
      Pancreatic function was considered normal when fecal elastase-1 concentration
      exceeded 200 MUg/g feces and moderately or severely insufficient when fecal
      elastas-1 concentration was less than 200 MUg/g feces. RESULTS: Of 123 patients
      who underwent PD, 67 (54.5%) showed fecal elastase-1 levels less than 200 MUg/g,
      indicating moderate or severe pancreatic insufficiency. Pancreas texture,
      pathology origin, and level of gamma-glutamyl transferase (r-GT) were
      significantly correlated with fecal elastas-1 level. On univariate analysis, the
      incidence of pancreatic leakage was significantly greater in the group with
      normal fecal elastase-1 level (>=200 MUg/g), pathologic origin (bile
      duct/ampulla/duodenum), and soft pancreas texture. In multivariate analysis,
      normal fecal elastase-1 level (>=200 MUg/g) and soft pancreatic texture were
      identified as independent factors for pancreatic leakage. CONCLUSIONS: Fecal
      elastase-1 is the most simple and objective method for predicting pancreatic
      leakage after PD.

PMID- 24038224
TI  - Development of UV/HPLC methods for quantitative analysis of benznidazole in human
      plasma and urine for application in pediatric clinical studies.
AB  - OBJECTIVE: Chagas disease constitutes a major public health problem in Latin
      America. Correctly designed pharmacokinetic, safety, and bioequivalence studies
      are desirable in order to fill the knowledge gaps that presently exist on
      available drugs. It is necessary to develop accurate, simple, reproducible, and
      sensitive high-performance liquid chromatography (HPLC)/UV methods for the
      quantization of benznidazole (BNZ) in human plasma and urine for clinical
      applications, specially in pediatric patients. METHODS: Quantization of BNZ in
      human plasma involved freeze-drying and re-suspension in organic solvent followed
      by reverse phase HPLC with UV detection. Analysis of BNZ in urine involved
      liquid/liquid extraction followed by reverse phase HPLC with UV detection.
      RESULTS: Limits of quantization (LOQ) were 0.32 MUg/ml for plasma and 5.2 MUg/ml
      for urine. No metabolite interferences were showed in both methods. CONCLUSION:
      The LOQ of methods seems appropriate in pediatric clinical contexts. Both
      procedures were applied with good results, to the quantization of BNZ in plasma
      and urine of patients treated for Chagas disease.

PMID- 24038225
TI  - Innovative accountability of tracking test kit as locked resources: a lesson in a
      restricted resource setting.
AB  - BACKGROUND: To implement quality screening in a blood service requires the
      presence of screening strategy with a clear algorithm and supporting standard
      operating procedures (SOPs), skilled and motivated human resource to perform
      testing, infrastructure, regular available test kits, and other supplies. In
      developing countries, smooth supply chain management of critical transfusion
      transmissible infections (TTIs) screening reagents is a challenge. Therefore,
      managing the little available kits by knowing the rate of consumption, good
      forecasting, and monitoring expiry date may be a key in ensuring regular supply.
      METHOD: Test kit monitoring tool (TKMT) for Vironostika HIV Uni-Form kit/192 1&2
      Ag/Ab, Genedia kits for HBsAg and HCV, and RPR for syphilis was developed to
      track these reagents. This excel tool was developed to assess received reagents,
      quantity used, quantity remaining, and date of expiration. The tool was evaluated
      by assessing rerun for each test kits, match tests conducted with blood units
      tested, adherence to the principle of first in-first out (FIFO), and quantity
      remaining in the center against the need. RESULTS: The mean rerun for HIV ELISA
      Vironistika uniform II Ag/Ab observed over expected was 6.9% (n = 3.8) than 2.4%
      (n = 1.3), HBsAg was 9.9% (n = 5.7) than 6.7% (3.5) (expected), Genedia for HCV
      was 1.3% (n = 0.7) than 0.5% (n = 0.3), and RPR test for syphilis 3.3% (n = 1.5)
      than 0.5%. During implementation, TKMT managed to detect expiring kits in the
      zonal blood transfusion centers. CONCLUSION: A tool-like TKMT may capture other
      supplies within blood when expanded. Monitoring of supplies may enable blood
      service actual accounting and in forecasting supplies and reagents.

PMID- 24038226
TI  - Does prolidase indicate worsening of hepatitis B infection?
AB  - BACKGROUND: Hepatitis B infection is a health problem that affects more than 400
      million people all over the world. We aimed to evaluate the usability of
      prolidase enzyme that plays an important role in collagen synthesis. Prolidase
      levels increase in hepatic damage, which can be used as diagnostic parameters in
      the progressions to chronic hepatitis B (CHB) infection by evaluating it in
      different clinical forms of hepatitis B infection. METHODS: A total of 69
      patients who presented to our clinic with chronic hepatitis B (CHB) infection, 72
      patients with inactive hepatitis B infection (IHB), and 45 healthy volunteers
      were included into this study. Alanine transaminase (ALT), Aspartate
      aminotransferase (AST) and prolidase levels of patients were measured. Hepatic
      biopsy was performed in patients with CHB infection. Prolidase levels were
      evaluated in three different groups, and its correlations with fibrosis were
      investigated. RESULTS: Prolidase was different between all groups (P < 0.001).
      Prolidase level was found to be higher in CHB and IHB compared to the control
      group. There was no correlation between this enzyme, fibrosis, and histological
      activity index. CONCLUSION: In this present study, it is shown that prolidase
      levels increase in hepatitis B infection. It may be used as a biochemical marker
      in the chronic hepatitis B.

PMID- 24038227
TI  - Stratified reporting of high sensitivity troponin I assay is associated with
      suboptimal management of patients with acute coronary syndrome and intermediate
      troponin elevation.
AB  - BACKGROUND: Newer troponin assays provide high sensitivity and precision and are
      reported in a stratified manner by some laboratories. We sought to investigate
      the clinical impact of such reporting in the treatment of patients with suspected
      acute coronary syndrome (ACS). METHODS: We identified patients presenting with
      suspected ACS over a one-year period. Patients were stratified based on their
      peak troponin I values within 24 hours of admission into the following categories
      as reported by our laboratory: troponin value <=0.03 ng/ml, which is reported as
      normal (negative troponin group), troponin value 0.04-0.29 ng/ml, which is
      reported as suggestive of myocardial damage (intermediate troponin group), and
      troponin value >=0.3 ng/ml which is reported as indicative of myocardial necrosis
      (high troponin group). RESULTS: Plasma troponin concentrations were <=0.03 ng/ml
      in 77 patients (68.7%), 0.04-0.29 ng/ml in 18 patients (16.1%), and >=0.30 ng/ml
      in 17 patients (15.2%). Patients in the intermediate troponin group had
      thrombolysis in myocardial infarction (TIMI) risk scores that were similar to
      that of the high troponin group. Despite this, patients in the intermediate
      troponin group were almost 50% less likely to receive coronary angiography,
      anticoagulation, and clopidogrel when compared to the high troponin group.
      CONCLUSION: Patients in the intermediate troponin group that meet the guideline
      definition of acute myocardial infarction are less likely to receive optimal
      medical and invasive therapy as compared to the high troponin group even though
      TIMI risk scores were similar in the two groups.

PMID- 24038228
TI  - Combination of white blood cell count and left shift level real-timely reflects a
      course of bacterial infection.
AB  - BACKGROUND: The efficacy of white blood cell (WBC) count and left shift in
      predicting bacterial infections has been controversial. The aim of this study was
      to prove that WBC count and left shift reflect a course of bacterial infection.
      MATERIALS: Six patients in whom the onset of bacterial infection had been
      determined and successful treatment had been done were selected. Manual 100-cell
      differential counts were repeated at least every 24 hr. RESULTS: WBC count and
      left shift divided a course of bacterial infection into five phases. In the first
      phase of bacterial infection (0-10 hr after the onset), WBC count decreased to
      fewer than reference range without left shift. In the second phase (about 10-20
      hr), low WBC count continued and left shift appeared. In the third phase (one to
      some days), WBC count increased above reference range with left shift. In the
      fourth phase (some to several days), high WBC count continued without left shift.
      In the fifth phase, WBC count went down into reference range without left shift.
      CONCLUSIONS: A combination of WBC count and left shift real-timely reflected a
      course of bacterial infection from the onset to healing. And we could judge which
      bacterial infection is adequately treated or not only by the above two routine
      laboratory tests.

PMID- 24038229
TI  - Risk factors for intensive care unit acquired nasal colonization of MRSA and its
      impact on MRSA infection.
AB  - OBJECTIVE: We aimed to determine the risk factors of methicillin-resistant
      Staphylococcus aureus (MRSA) colonization, and the impact of colonization on MRSA
      infection to evaluate the necessity of MRSA survey program in intensive care
      units (ICUs) in Turkey. METHODS: The patients hospitalized in medical and
      neurosurgical ICUs longer than 24 hr were included into the study. To determine
      anterior nares MRSA colonization, swabs were taken from each patient in the first
      48 hr, and followed by once a week till discharge from ICUs. RESULTS: During the
      one-year follow-up period, the number of the hospitalized patients who spent more
      than 24 hr in ICUs was 195 of 372 and 85 of 619 in medical and neurosurgical
      ICUs, respectively. Totally, 23 out of 280 patients (14 from medical ICU, 9 from
      neurosurgical ICU) were colonized with MRSA, and 11 out of 23 colonized patients
      were accepted as ICU-acquired infection. The duration of ICU hospitalization in
      patients with ICU-acquired MRSA colonization was found to be longer than the
      noncolonized patients (18 days vs. 8 days, P value < 0.001). The presence of
      gastrostomy and femoral catheter were determined as risk factors for ICU-acquired
      MRSA colonization. The percentages of MRSA infection in patients with and without
      MRSA colonized were 8.6% and 1.1%, respectively (P value: 0.009). CONCLUSION: The
      presence of gastrostomy and femoral catheter, and the duration of ICU
      hospitalization were found to be related with ICU-acquired MRSA colonization.
      Also, MRSA nares colonization increased the rates of both MRSA infection and ICU
      hospitalization.

PMID- 24038230
TI  - Comparison of hemagglutination inhibition assay and enzyme immunoassay for
      determination of mumps and rubella immune status in health care personnel.
AB  - BACKGROUND: Screening tests are available to determine immunity to vaccine
      preventable diseases, such as mumps and rubella. We aimed to define better assay
      for detecting immune status of health care personnel to vaccine-preventable
      diseases. METHODS: Mumps and rubella antibodies of health care personnel at
      Shimane University Hospital were examined by hemagglutination inhibition assay
      (HI), comparing with those by enzyme immunoassay (EIA). RESULTS: A total of 910
      sera from health care personnel were tested. There was poor correlation between
      HI and EIA in detecting mumps antibodies with correlation coefficient values (r)
      = 0.190 (P < 0.001), but in rubella antibodies HI and EIA were relatively well
      correlated (r = 0.930, P < 0.001). Seropositivity rate of HI versus EIA was found
      to be 65.7 versus 93.2, and 89.5 versus 86.5% for mumps and rubella,
      respectively. As compared with EIA, HI identified sixfold larger seronegative
      subjects in mumps. Moreover, in mumps, 88.8% of seronegative subjects detected by
      HI were seropositive by EIA, while 3.7% of seropositive subjects detected by HI
      were seronegative by EIA. In rubella, 2.1% of seronegative subjects detected by
      HI were seropositive by EIA, and 1.7% of seropositive by HI was seronegative by
      EIA. CONCLUSION: Considerable difference between HI and EIA in determining immune
      status of health care personnel to mumps and rubella suggests beneficial use of
      EIA for the identification of accurate susceptible personnel who subsequently
      undergo an effective vaccination programs. Seroprevalence survey of health care
      personnel by using appropriate assay is essential for prevention and infection
      control strategies in health care settings.

PMID- 24038231
TI  - Early modulation by the dopamine D4 receptor of morphine-induced changes in the
      opioid peptide systems in the rat caudate putamen.
AB  - The peptides dynorphin and enkephalin modulate many physiological processes, such
      as motor activity and the control of mood and motivation. Their expression in the
      caudate putamen (CPu) is regulated by dopamine and opioid receptors. The current
      work was designed to explore the early effects of the acute activation of D4
      and/or MU opioid receptors by the agonists PD168,077 and morphine, respectively,
      on the regulation of the expression of these opioid peptides in the rat CPu, on
      transcription factors linked to them, and on the expression of MU opioid
      receptors. In situ hybridization experiments showed that acute treatment with
      morphine (10 mg/kg) decreased both enkephalin and dynorphin mRNA levels in the
      CPu after 30 min, but PD168,077 (1 mg/kg) did not modify their expression.
      Coadministration of the two agonists demonstrated that PD168,077 counteracted the
      morphine-induced changes and even increased enkephalin mRNA levels. The
      immunohistochemistry studies showed that morphine administration also increased
      striatal MU opioid receptor immunoreactivity but reduced P-CREB expression,
      effects that were blocked by the PD168,077-induced activation of D4 receptors.
      The current results present evidence of functional D4 -MU opioid receptor
      interactions, with consequences for the opioid peptide mRNA levels in the rat
      CPu, contributing to the integration of DA and opioid peptide signaling.

PMID- 24038232
TI  - Assessing interchangeability at cluster levels with multiple-informant data.
AB  - Studies examining the relationship between neighborhood social disorder and
      health often rely on multiple informants. Such studies assume interchangeability
      of the latent constructs derived from multiple-informant data. Existing methods
      examining this assumption do not clearly delineate the uncertainty at individual
      levels from that at neighborhood levels. We propose a multilevel variance
      component factor model that allows this delineation. Data come from a survey of a
      representative sample of children born between 1983 and 1985 in the inner city of
      Detroit and nearby middle-class suburbs. Results indicate that the informant
      level models tend to exaggerate the effect of places because of differences
      between persons. Our evaluations of different methodologies lead to the
      recommendation of the multilevel variance component factor model whenever
      multiple-informant reports can be aggregated at a neighborhood level.

PMID- 24038233
TI  - How well are we controlling falls from height in construction? Experiences of
      union carpenters in Washington State, 1989-2008.
AB  - BACKGROUND: Falls from height (FFH) continue to cause significant morbidity and
      mortality across the construction industry. METHODS: By linking data on work
      hours with workers' compensation records, rates of work-related injuries
      resulting from FFH and associated days away from work were evaluated among a
      large cohort (n = 24,830) of union carpenters in Washington State from 1989 to
      2008. Using Poisson regression we assessed rates of FFH over the 20-year period
      while adjusting for temporal trend in other work-related injuries. Patterns of
      paid lost days (PLDs) were assessed with negative binomial regression. RESULTS:
      Crude rates of FFH decreased 82% over the 20-year period. Reductions were more
      modest and without demonstrable change since 1996 when adjusting for the temporal
      reduction in other injuries. Younger workers had higher injury rates; older
      workers lost more days following falls. Rates of PLDs associated with falls
      decreased over time, but there was not a consistent decline in mean lost days per
      fall. CONCLUSION: These patterns are consistent with decreased FFH for several
      years surrounding state (1991) and then federal (1994) fall standards; the
      decline during this time period exceeded those seen in injury rates overall in
      this cohort. While crude rates of FFH have continued to decline, the decline is
      not as substantial as that seen for other types of injuries. This could reflect a
      variety of things including more global efforts designed to control risk (site
      planning, safety accountability) and changes in reporting practices.

PMID- 24038234
TI  - Navigating in small-scale space: the role of landmarks and resource monitoring in
      understanding saddleback tamarin travel.
AB  - Recent studies of spatial memory in wild nonhuman primates indicate that foragers
      may rely on a combination of navigational strategies to locate nearby and distant
      feeding sites. When traveling in large-scale space, tamarins are reported to
      encode spatial information in the form of a route-based map. However, little is
      known concerning how wild tamarins navigate in small-scale space (between feeding
      sites located at a distance of <=60 m). Therefore, we collected data on range
      use, diet, and the angle and distance traveled to visit sequential feeding sites
      in the same group of habituated Bolivian saddleback tamarins (Saguinus
      fuscicollis weddelli) in 2009 and 2011. For 7-8 hr a day for 54 observation days,
      we recorded the location of the study group at 10 min intervals using a GPS unit.
      We then used GIS software to map and analyze the monkeys' movements and travel
      paths taken between feeding sites. Our results indicate that in small-scale space
      the tamarins relied on multiple spatial strategies. In 31% of cases travel was
      route-based. In the remaining 69% of cases, however, the tamarins appeared to
      attend to the spatial positions of one or more near-to-site landmarks to relocate
      feeding sites. In doing so they approached the same feeding site from a mean of
      4.5 different directions, frequently utilized different arboreal pathways, and
      traveled approximately 30% longer than then the straight-line distance. In
      addition, the monkeys' use of non-direct travel paths allowed them to monitor
      insect and fruit availability in areas within close proximity of currently used
      food patches. We conclude that the use of an integrated spatial strategy (route
      based travel and attention to near-to-goal landmarks) provides tamarins with the
      opportunity to relocate productive feeding sites as well as monitor the
      availability of nearby resources in small-scale space.

PMID- 24038235
TI  - Click construction of spiro- and bridged-quatrefoil polymer topologies with kyklo
      telechelics having an azide group.
AB  - Unprecedented tetracyclic polymer topologies with spiro- and a bridged-type
      quatrefoil forms are effectively constructed through an alkyne-azide, click
      linking reaction by employing a kyklo-telechelic poly(tetrahydrofuran),
      poly(THF), precursor having an azide group, obtained through an electrostatic
      self-assembly and covalent fixation (ESA-CF) process, and complementary
      tetrafunctional alkyne reagents of either a pentaerythritol derivative or a four
      armed star telechelic polymer precursor. 

PMID- 24038237
TI  - sigma-Hole bond versus hydrogen bond: from tetravalent to pentavalent N, P, and
      as atoms.
AB  - Ab initio calculations were performed on complexes of ZH4 (+) (Z=N, P, As) and
      their fluoro derivatives, ZFH3 (+) and ZF4 (+) , with a HCN (or LiCN) molecule
      acting as the Lewis base through the nitrogen electronegative center. It was
      found that the complexes are linked by the Z?H???N hydrogen bond or another type
      of noncovalent interaction in which the tetravalent heavy atom of the cation acts
      as the Lewis acid center, that is, when the Z???N link exists, which may be
      classified as the sigma-hole bond. The formation of the latter interaction is
      usually preferable to the formation of the corresponding hydrogen bond. The Z???N
      interaction may be also considered as the preliminary stage of the SN 2 reaction.
      This is supported by the observation that for a short Z???N contact, the
      corresponding complex geometry coincides with the trigonal-bipyramidal geometry
      typical for the transition state of the SN 2 reaction. The Z???N interaction for
      some of complexes analyzed here possesses characteristics typical for covalent
      bonds. Numerous interrelations between geometrical, topological and energetic
      parameters are discussed. The natural bond orbital method as well as the Quantum
      Theory of "Atoms in Molecules" is applied to characterize interactions in the
      analyzed complexes. The experimental evidences of the existence of these
      interactions, based on the Cambridge Structure Database search, are also
      presented. In addition, it is justified that mechanisms of the formation of the
      Z???N interactions are similar to the processes occurring for the other
      noncovalent links. The formation of Z???N interaction as well as of other
      interactions may be explained with the use of the sigma-hole concept. 

PMID- 24038236
TI  - Unfavorable hip stress distribution after Legg-Calve-Perthes syndrome: a 25-year
      follow-up of 135 hips.
AB  - To study the effect of hip and pelvis geometry on development of the hip after
      Perthes disease, we determined the resultant hip force and contact hip stress
      distribution in a population of 135 adult hips of patients who had been treated
      for Perthes disease in childhood. Contra-lateral hips with no record of disease
      were taken as the control population. Biomechanical parameters were determined by
      mathematical models for resultant hip force in one-legged stance and for contact
      hip stress, which use as an input the geometrical parameters assessed from
      anteroposterior radiographs. The mathematical model for stress was upgraded to
      account for the deviation of the femoral head shape from spherical. No
      differences were found in resultant hip force and in peak contact hip stress
      between the hips that were in childhood subject to Perthes disease and the
      control population, but a considerable (148%) and significant (p < 0.001)
      difference was found in the contact hip stress gradient index, expressing an
      unfavorable, steep decrease of contact stress at the lateral acetabular rim. This
      finding indicates an increased risk of early coxarthritis in hips subject to
      Perthes disease.

PMID- 24038238
TI  - Association between polymorphism of beta3-adrenoceptor gene and overactive
      bladder.
AB  - AIMS: In human urinary bladder, beta3-ARs play an important role in promoting
      detrusor relaxation during the storage phase of the micturition cycle. The
      present study investigated whether a Trp64Arg polymorphism of the gene encoding
      the beta3-AR is associated with overactive bladder (OAB) syndrome. METHODS: This
      study involved 100 women with OAB and 101 healthy control women without OAB. Hair
      root samples were obtained from all subjects and used for beta3-AR gene analysis.
      Polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)
      analysis was performed to analyze a polymorphism in the gene of Trp64Arg.
      RESULTS: The overall frequency of the 64Arg variant (heterozygous plus
      homozygous) in OAB patients was 47% and significantly higher than the frequency
      of 22.8% found in non-OAB control women. Within OAB patients, numbers of
      micturitions per day, urgency episodes per day, and urgency incontinence episodes
      per day in the 64Arg variant carriers were not significantly different from those
      in the normal gene carriers. CONCLUSIONS: This study shows that the Trp64Arg
      polymorphism in the beta3-AR gene is weakly but significantly associated with OAB
      syndrome.

PMID- 24038239
TI  - Effect of cyanide ligands on the electronic structure of [FeFe] hydrogenase
      active-site model complexes with an azadithiolate cofactor.
AB  - A detailed characterization of a close synthetic model of the [2 Fe]H subcluster
      in the [FeFe] hydrogenase active site is presented. It contains the full primary
      coordination sphere of the CO-inhibited oxidized state of the enzyme including
      the CN(-) ligands and the azadithiolate (adt) bridge, [((MU-S?CH2 )2 NR)Fe2 (CO)4
      (CN)2 ](2-) , R=CH2 CH2 SCH3 . The electronic structure of the model complex in
      its Fe(I) Fe(II) state was investigated by means of density functional theory
      (DFT) calculations and Fourier transform infrared (FTIR) spectroscopy. By using a
      combination of continuous-wave (CW) electron paramagnetic resonance (EPR) and
      hyperfine sublevel correlation (HYSCORE) experiments as well as DFT calculations,
      it is shown that, for this complex, the spin density is delocalized over both
      iron atoms. Interestingly, we found that the nitrogen hyperfine coupling, which
      represents the interaction between the unpaired electron and the nitrogen at the
      dithiolate bridge, is slightly larger than that in the analogous complex in which
      the CN(-) ligands are replaced with PMe3 ligands. This reveals, first, that the
      CN(-) /PMe3 ligands coordinated to the iron core are electronically coupled to
      the amine in the adt bridge. Second, the CN(-) ligands in this complex are
      somewhat stronger sigma-donor ligands than the PMe3 ligand, and thereby enable
      more spin density to be transferred from the Fe core to the adt unit, which might
      in turn affect the reactivity of the bridging amine. 

PMID- 24038240
TI  - Measurement of plasma, serum, and platelet serotonin in individuals with high
      bone mass and mutations in LRP5.
AB  - It has recently been suggested that the low-density lipoprotein receptor-related
      protein 5 (LRP5) regulates bone mass by suppressing secretion of serotonin from
      duodenal enterochromaffin cells. In mice with targeted expression of a high bone
      mass-causing (HBM-causing) LRP5 mutation and in humans with HBM LRP5 mutations,
      circulating serotonin levels have been reported to be lower than in controls
      whereas individuals with loss-of-function mutations in LRP5 have high blood
      serotonin. In contrast, others have reported that conditionally activating a
      knock-in allele of an HBM-causing LRP5 mutation in several tissues, or genetic
      deletion of LRP5 in mice has no effect on serum serotonin levels. To further
      explore the possible association between HBM-causing LRP5 mutations and
      circulating serotonin, levels of the hormone were measured in the platelet poor
      plasma (PPP), serum, and platelet pellet (PP) of 16 affected individuals from 2
      kindreds with HBM-causing LRP5 mutations (G171V and N198S) and 16 age-matched
      controls. When analyzed by HPLC, there were no differences in levels of serotonin
      in PPP and PP between affected individuals and age-matched controls. Similarly,
      when analyzed by ELISA, there were no differences in PPP or PP between these two
      groups. By ELISA, serum levels of serotonin were higher in the affected
      individuals when compared to age-matched controls. A subgroup analysis of only
      the G171V subjects (n=14) demonstrated that there were no differences in PPP and
      PP serotonin between affected individuals and controls when analyzed by HPLC. PP
      serotonin was lower in the affected individuals when measured by ELISA but serum
      serotonin levels were not different. We conclude that there is no change in PPP
      serotonin in individuals with HBM-causing mutations in LRP5.

PMID- 24038241
TI  - What are we assessing when we measure food security? A compendium and review of
      current metrics.
AB  - The appropriate measurement of food security is critical for targeting food and
      economic aid; supporting early famine warning and global monitoring systems;
      evaluating nutrition, health, and development programs; and informing government
      policy across many sectors. This important work is complicated by the multiple
      approaches and tools for assessing food security. In response, we have prepared a
      compendium and review of food security assessment tools in which we review issues
      of terminology, measurement, and validation. We begin by describing the evolving
      definition of food security and use this discussion to frame a review of the
      current landscape of measurement tools available for assessing food security. We
      critically assess the purpose/s of these tools, the domains of food security
      assessed by each, the conceptualizations of food security that underpin each
      metric, as well as the approaches that have been used to validate these metrics.
      Specifically, we describe measurement tools that 1) provide national-level
      estimates of food security, 2) inform global monitoring and early warning
      systems, 3) assess household food access and acquisition, and 4) measure food
      consumption and utilization. After describing a number of outstanding measurement
      challenges that might be addressed in future research, we conclude by offering
      suggestions to guide the selection of appropriate food security metrics. 

PMID- 24038243
TI  - Impact of new-generation parenteral lipid emulsions in pediatric nutrition.
AB  - Advancements in the care of premature infants and infants with severe bowel
      disease have occurred in which long-term use of i.v. nutrition is a cornerstone
      of successful therapy. Concern about the role of i.v. lipid emulsions in causing
      severe liver damage to high-risk infants receiving long-term i.v. nutrition has
      led to a variety of intervention strategies. These have had relatively limited
      success until the recent introduction of omega-3 (n-3) fatty acid-containing
      forms of lipid emulsions in place of the current omega-6 fatty acid-predominant
      lipid emulsions currently exclusively used in the United States. Preliminary data
      based on nonrandomized trials performed using compassionate-use protocols in the
      United States suggest very high rates of resolution of cholestasis with the use
      of an omega-3 fatty acid-predominant lipid emulsion. This result is supported by
      animal models of liver disease that demonstrate decreased liver damage when
      animals are provided omega-3 fatty acid-containing lipid emulsions compared with
      those primarily omega-6 fatty acid based. However, human trials are limited at
      this time and further research is needed to establish the best approach to
      preventing liver damage in infants receiving i.v. nutrition and the optimal dose
      and timing of intervention with novel lipid emulsions. 

PMID- 24038244
TI  - The role of nutritional research in the success of human space flight.
AB  - The United States has had human space flight programs for >50 y and has had a
      continued presence in space since 2000. Providing nutritious and safe food is
      imperative for astronauts because space travelers are totally dependent on
      launched food. Space flight research topics have included energy, protein,
      nutritional aspects of bone and muscle health, and vision issues related to 1
      carbon metabolism. Research has shown that energy needs during flight are similar
      to energy needs on Earth. Low energy intakes affect protein turnover. The type of
      dietary protein is also important for bone health, plant-based protein being more
      efficacious than animal protein. Bone loss is greatly ameliorated with adequate
      intakes of energy and vitamin D, along with routine resistive exercise.
      Astronauts with lower plasma folate concentrations may be more susceptible to
      vision changes. Foods for space flight were developed initially by the U.S. Air
      Force School of Aerospace Medicine in conjunction with the U.S. Army Natick
      Laboratories and NASA. Hazard Analysis Critical Control Point safety standards
      were specifically developed for space feeding. Prepackaged foods for the
      International Space Station were originally high in sodium (5300 mg/d), but NASA
      has recently reformulated >90 foods to reduce sodium intake to 3000 mg/d. Food
      development has improved nutritional quality as well as safety and acceptability.

PMID- 24038245
TI  - Building evidence for sustainability of food and nutrition intervention programs
      in developing countries.
AB  - After making large investments to put in place effective health and nutrition
      interventions, researchers, program implementers, policy makers, and donors all
      expect lasting effects. However, it is uncertain whether this is the case, and
      there is less certainty on how to approach the study of program sustainability.
      This symposium, "Building Evidence for Sustainability of Food and Nutrition
      Intervention Programs in Developing Countries," provided not only frameworks for
      conceptualizing sustainability but concrete evidence about the approaches and
      methods used as well as lessons on how they do or do not work in particular
      contexts. We presented the following findings: 1) sustainability of activities
      and impacts of Title II food aid programs in Bolivia and Kenya, 2) sustainability
      of impact in terms of adoption and consumption of a biofortified orange sweet
      potato in Uganda, and 3) lessons from incorporating pro-sustainability investment
      strategies in child survival programs in Guinea. Our symposium introduced a new
      important body of research on program sustainability to provide insights and
      stimulate innovative thinking in the design and planning of further applied
      research and future prosustainability intervention programs. 

PMID- 24038246
TI  - Sweetened beverages and health: current state of scientific understandings.
AB  - This article summarizes the presentations from the "Sweetened Beverages and
      Health: Current State of Scientific Understandings" symposium held at the ASN
      Annual Meeting in Boston, MA on April 23, 2013. The metabolic and health effects
      of sugar-sweetened beverages were discussed from a variety of points of view by 5
      different presenters. Dr. David Allison drew a distinction between conjecture and
      proof related to sweetened beverages and obesity. Dr. Richard Mattes discussed
      differences between solid and liquid calories. Dr. Miguel Alonso-Alonso reviewed
      potential contributions of functional neuroimaging, particularly as they relate
      to whether sugar is potentially "addictive." Dr. Kimber Stanhope discussed work
      related to experiments comparing fructose to glucose. Dr. James Rippe presented
      evidence from randomized controlled trials from his research organization showing
      no differences among high-fructose corn syrup, sucrose, glucose, or fructose at
      normal human consumption amounts. 

PMID- 24038247
TI  - Nutritional epigenomics: a portal to disease prevention.
AB  - Epigenetics can be defined as inheritable and reversible phenomena that affect
      gene expression without altering the underlying base pair sequence. Epigenomics
      is the study of genome-wide epigenetic modifications. Because gene expression
      changes are critical in both normal development and disease progression,
      epigenetics is widely applicable to many aspects of biological research. The
      influences of nutrients and bioactive food components on epigenetic phenomena
      such as DNA methylation and various types of histone modifications have been
      extensively investigated. Because an individual's epigenetic patterns are
      established during early gestation and are changed and personalized by
      environmental factors during our lifetime, epigenetic mechanisms are quite
      important in the development of transgenerational and adult obesity as well as in
      the development of diabetes mellitus. Aging and cancer demonstrate profound
      genome-wide DNA methylation changes, suggesting that nutrition may affect the
      aging process and cancer development through epigenetic mechanisms. 

PMID- 24038242
TI  - Mineral malnutrition following bariatric surgery.
AB  - Moderate/severe obesity is on the rise in the United States. Weight management
      includes bariatric surgery, which is effective and can alleviate morbidity and
      mortality from obesity-associated diseases. However, many individuals are dealing
      with nutritional complications. Risk factors include: 1) preoperative
      malnutrition (e.g., vitamin D, iron); 2) decreased food intake (due to reduced
      hunger and increased satiety, food intolerances, frequent vomiting); 3)
      inadequate nutrient supplementation (due to poor compliance with
      multivitamin/multimineral regimen, insufficient amounts of vitamins and/or
      minerals in supplements); 4) nutrient malabsorption; and 5) inadequate
      nutritional support (due to lack of follow-up, insufficient monitoring,
      difficulty in recognizing symptoms of deficiency). For some nutrients (e.g.,
      protein, vitamin B-12, vitamin D), malnutrition issues are reasonably addressed
      through patient education, routine monitoring, and effective treatment
      strategies. However, there is little attention paid to other nutrients (e.g.,
      zinc, copper), which if left untreated may have devastating consequences (e.g.,
      hair loss, poor immunity, anemia, defects in neuro-muscular function). This
      review focuses on malnutrition in essential minerals, including calcium (and
      vitamin D), iron, zinc, and copper, which commonly occur following popular
      bariatric procedures. There will be emphasis on the complexities, including
      confounding factors, related to screening, recognition of symptoms, and, when
      available, current recommendations for treatment. There is an exceptionally high
      risk of malnutrition in adolescents and pregnant women and their fetuses, who may
      be vulnerable to problems in growth and development. More research is required to
      inform evidence-based recommendations for improving nutritional status following
      bariatric surgery and optimizing weight loss, metabolic, and nutritional
      outcomes. 

PMID- 24038248
TI  - Iodine insufficiency: a global health problem?
AB  - As a result of collaborative efforts with international organizations and the
      salt industry, many developing and developed countries practice universal salt
      iodization (USI) or have mandatory salt fortification programs. As a consequence,
      the prevalence of iodine deficiency decreased dramatically. The United States and
      Canada are among the few developed countries that do not practice USI. Such an
      undertaking would require evidence of deficiency among vulnerable population
      groups, including pregnant women, newborns, and developing infants. Government
      agencies in the United States rely heavily on data from NHANES to assess the
      iodine status of the general population and pregnant women in particular. NHANES
      data suggest that pregnant women in the United States remain mildly deficient.
      This is important, because the developing fetus is dependent on maternal iodine
      intake for normal brain development throughout pregnancy. Professional societies
      have recommended that pregnant and lactating women, or those considering
      pregnancy, consume a supplement providing 150 MUg iodine daily. The United States
      and Canada collaborate on the daily recommended intake and are also confronted
      with the challenge of identifying the studies needed to determine if USI is
      likely to be beneficial to vulnerable population groups without exposing them to
      harm. 

PMID- 24038249
TI  - Exploring culture in the world of international nutrition and nutrition sciences.
AB  - This symposium was organized to bring insights from the social sciences into the
      awareness of nutrition scientists committed to developing and implementing
      effective nutrition interventions internationally. The symposium explored three
      different areas in the field where a more precise analysis of culture could
      enhance the effectiveness of nutrition science: 1) in the implementation of
      nutrition science research in the field; 2) in the collaboration of multiple
      stakeholders working to enhance nutrition in a national setting; and 3) in the
      language and discussions used to frame proposed changes in large scale food and
      nutrition security policy transnationally. Three social scientists, Monique
      Centrone Stefani, Lucy Jarosz, and David Pelletier were invited to share insights
      from their respective disciplines and respondents from within the field of
      nutrition provided initial reflections to better understand such perspectives.
      The symposium's interdisciplinary nature was designed to illustrate the challenge
      of multiple perspectives and methodologies and to advance understanding that
      could derive from such an exchange for those in the field of international
      nutrition seeking to decrease global hunger and malnutrition. 

PMID- 24038250
TI  - Are dietary bioactives ready for recommended intakes?
AB  - Research has shown that numerous dietary bioactive components that are not
      considered essential may still be beneficial to health. The dietary reference
      intake (DRI) process has been applied to nonessential nutrients, such as fiber,
      yet the majority of bioactive components await a recommended intake. Despite a
      plethora of new research over the past several years on the health effects of
      bioactives, it is possible that the field may never reach a point where the
      current DRI framework is suitable for these food components. If bioactives are to
      move toward dietary guidance, they will likely require an alternative path to get
      there. 

PMID- 24038251
TI  - Dietary phosphorus excess: a risk factor in chronic bone, kidney, and
      cardiovascular disease?
AB  - There is growing evidence in the nephrology literature supporting the deleterious
      health effect of excess dietary phosphorus intake. This issue has largely escaped
      the attention of nutrition experts until this symposium, which raised the
      question of whether the same health concerns should be extended to the general
      population. The potential hazard of a high phosphorus intake in the healthy
      population is illustrated by findings from acute and epidemiologic studies. Acute
      studies in healthy young adults demonstrate that phosphorus intakes in excess of
      nutrient needs may significantly disrupt the hormonal regulation of phosphorus
      contributing to disordered mineral metabolism, vascular calcification, bone loss,
      and impaired kidney function. One of the hormonal factors acutely affected by
      dietary phosphorus loading is fibroblast growth factor-23, which may be a key
      factor responsible for many of the cardiovascular disease (CVD) complications of
      high phosphorus intake. Increasingly, large epidemiological studies suggest that
      mild elevations of serum phosphorus within the normal range are associated with
      CVD risk in healthy populations. Few population studies link high dietary
      phosphorus intake to mild changes in serum phosphorus due to study design issues
      specific to phosphorus and inaccurate nutrient composition databases. The
      increasing phosphorus intake due to the use of phosphorus-containing ingredients
      in processed food and the growing consumption of processed convenience and fast
      foods is an important factor that needs to be emphasized. 

PMID- 24038252
TI  - Strategies to optimize the impact of nutritional surveys and epidemiological
      studies.
AB  - The development of nutrition and health guidelines and policies requires reliable
      scientific information. Unfortunately, theoretical considerations and empirical
      evidence indicate that a large percentage of science-based claims rely on studies
      that fail to replicate. The session "Strategies to Optimize the Impact of
      Nutrition Surveys and Epidemiological Studies" focused on the elements of design,
      interpretation, and communication of nutritional surveys and epidemiological
      studies to enhance and encourage the production of reliable, objective evidence
      for use in developing dietary guidance for the public. The speakers called for
      more transparency of research, raw data, consistent data-staging techniques, and
      improved data analysis. New approaches to collecting data are urgently needed to
      increase the credibility and utility of findings from nutrition epidemiological
      studies. Such studies are critical for furthering our knowledge and understanding
      of the effects of diet on health. 

PMID- 24038253
TI  - Metabolic profiling in nutrition and metabolic disorders.
AB  - Nutrients exert potent effects on metabolism through a variety of regulatory
      mechanisms, resulting in local and systemic changes in metabolite levels.
      Numerous studies have focused on mechanisms by which nutrients and disease states
      regulate metabolism at the gene or protein levels using genomic and proteomic
      approaches, respectively. However, few studies have investigated nutritional
      regulation of the whole metabolome. Thus, metabolomic approaches have recently
      emerged to complement the genomics and proteomics research and to help identify
      biologically meaningful metabolites and metabolic networks that control cellular
      responses to genetic and environmental factors, including diet, and to identify
      metabolic diseases that are influenced by genetic and dietary factors. These
      large-scale studies expedite our ability to develop targeted treatments. The goal
      of this symposium was to provide a forum to introduce the metabolomics field to
      nutrition researchers. An overview of the state-of-the-art metabolomic
      technologies used was provided. The impact of some specific nutrients, disease
      states, or genetic variations and their interaction with the metabolome was
      discussed by the speakers. Our objectives were as follows: 1) to educate the
      audience about the use of metabolomics as an innovative tool for linking changes
      in cell metabolites and genetic variations to nutrient metabolism, energy
      balance, and the overlying effects on health and disease; 2) to understand the
      concept of metabolomics and describe the analytical tools and resources available
      in this area; 3) to introduce the potential application of metabolomics in the
      field of nutrition research; and 4) to provide specific nutrition-relevant
      metabolomics study examples in investigating regulation of the metabolic network
      or metabolic changes resulting from disease states by dietary factors. 

PMID- 24038254
TI  - Life course epidemiology in nutrition and chronic disease research: a timely
      discussion.
AB  - Humans are exposed to a complex and changing combination of nutritional factors
      during the life course, necessitating their investigation over time to capture
      "critical periods of sensitivity." A life course approach provides a framework to
      examine trajectories and long-term effects of nutritional and other risk factors,
      particularly the role of timing, accumulation, and temporal relationships of
      these exposures in relation to chronic disease development. Currently, most
      epidemiologic research does not sufficiently address this issue in relation to
      disease etiology. Although applying a life course approach would augment our
      knowledge about disease development, this approach presents major challenges in
      designing, conducting, and analyzing studies. A scientific symposium was held
      that reviewed emerging research and discussed methodological concerns in applying
      the life course approach. The research presented at this session focused on the
      role of timing, with the pre- and postnatal and pubertal periods as critical
      windows of exposure for chronic conditions. Methodological issues and
      complexities in analyzing and selecting datasets were highlighted. This symposium
      elucidated unique study designs and statistical strategies to demonstrate the
      strengths of this methodology, and served as a catalyst for new research in the
      area of nutrition and chronic disease epidemiology. 

PMID- 24038255
TI  - Brain imaging and human nutrition: which measures to use in intervention studies?
AB  - Throughout the life span, the brain is a metabolically highly active organ that
      uses a large proportion of total nutrient and energy intake. Furthermore, the
      development and repair of neural tissue depend on the proper intake of essential
      structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain
      from eating, may have an important impact on our cognitive ability and mental
      performance. Two of the key areas in which diet is thought to play an important
      role are in optimizing neurodevelopment in children and in preventing
      neurodegeneration and cognitive decline during aging. From early development to
      aging, brain imaging can detect structural, functional, and metabolic changes in
      humans and modifications due to altered nutrition or to additional nutritional
      supplementation. Inclusion of imaging measures in clinical studies can increase
      understanding with regard to the modification of brain structure, metabolism, and
      functional endpoints and may provide early sensitive measures of long-term
      effects. In this symposium, the utility of existing brain imaging technologies to
      assess the effects of nutritional intervention in humans is described. Examples
      of current research showing the utility of these markers are reviewed. 

PMID- 24038256
TI  - The WHO evidence-informed guideline development process and implications for
      vitamin and mineral research priorities: symposium rationale and summary.
AB  - The WHO evidence-informed guidelines provide recommendations to Member States and
      their partners on interventions with vitamins and minerals. Evidence gathered and
      synthesized through systematic reviews contributes to the development of these
      guidelines, a process that is dependent on the availability and quality of
      evidence. Although the guideline development process is stringently governed and
      supervised to maintain clarity and transparency, the lack of adequacy and
      specificity of available evidence poses limitations to the formulation of
      recommendations that can be easily applied for policy and program decision making
      in diverse contexts. The symposium created a space for dialogue among scientists
      and public health practitioners to improve the understanding of how evidence
      fulfills the needs and reflect on mechanisms by which policy and program guidance
      and priorities for research could be better informed by policy and program needs.
      Ultimately, programmatic success depends not only on identifying efficacious
      agents but ensuring effective delivery to those with the potential to respond. To
      do this, we must understand the rationale for recommending interventions, the
      biological pathways by which interventions work, delivery systems required to
      make efficacious interventions work, and other contextual factors that might
      limit or facilitate successful implementation. 

PMID- 24038257
TI  - Assessing U.S. sodium intake through dietary data and urine biomarkers.
AB  - Sodium intake is related to blood pressure, an established risk factor for heart
      disease and stroke. Reducing intake may save billions in United States health
      care dollars annually. Efforts targeting sodium reductions make accurate
      monitoring vital, yet limited information exists on the accuracy of the current
      data to assess sodium intake in the United States population. In this symposium,
      new findings were presented on the accuracy of estimating population 24-h urinary
      excretion of sodium from spot urine specimens or sodium intake from 24-h dietary
      recalls. Differences in accuracy by sex, BMI, and race were apparent as well as
      by timing of spot urine collections. Although some published equations appear
      promising for estimating group means, others are biased. Individual estimates of
      sodium intake were highly variable and adjustment for within-individual variation
      in intake is required for estimating population prevalence or percentiles.
      Estimates indicated United States sodium intake remains high. 

PMID- 24038258
TI  - Update on human calorie restriction research.
AB  - The United States population is aging rapidly, and understanding the potential
      impact and feasibility of lifestyle interventions on the aging process is of
      central importance for addressing future population health and health care costs.
      This symposium addressed the question of whether caloric restriction may be a
      feasible strategy to improve human health by reductions in rates of primary and
      secondary aging in humans, viewed from the perspective of existing data in animal
      models, and by using emerging data from the human Comprehensive Assessment of
      Long-Term Reduction in Energy Intake trial, which is a randomized trial of human
      caloric restriction in free-living men and women. 

PMID- 24038259
TI  - Lipidomics technologies at the end of the first decade and the beginning of the
      next.
AB  - The lipidome is composed of all of the biomolecules defined as lipids, which
      encompass compounds of amazing structural diversity and complexity. It has been
      ~1 decade since the study of "lipidomics" was begun in earnest, and the
      technologies and tools for data analysis have advanced considerably over this
      period. This workshop summarized the scope of the lipidome and technologies for
      its analysis, lipidomics databases and other online tools, and examples of the
      application of lipidomics to nutritional research. The slides from the workshop,
      online lipidomics tools, and databases are available at http://www.lipidmaps.org.

PMID- 24038260
TI  - Comparative metabolic physiology in the 'omics' era: a call to arms, paws,
      flippers, and claws.
AB  - In nutrition, medicine, and animal science, metabolism research is often focused
      on solving questions using a single organism. Outcomes are most often linked to
      translational outcomes, understanding or treating a disease, optimizing
      nutritional status, improving select qualities of production animals, which have
      tremendous value to human and animal health as well as economic benefit. There is
      also value in clarifying basic biological principles and integrative systems that
      determine how organisms function and deal with their environment. Relevant to
      both translational and basic research questions, comparative metabolic physiology
      provides a context by which new "omics" technologies and other approaches can be
      coupled to multi-species metabolic phenotype diversity. These principles were
      highlighted at the "Adipose and Lipid Biology: Crossing Taxonomic Boundaries"
      symposium held at the 2013 Experimental Biology meeting in Boston, MA. By
      considering differences and shared physiology across a spectrum of phenotypes
      (especially when considering "extremes" that have emerged from evolutionary
      processes or breeding selection), one may unmask subtle processes and learn from
      natural adaptations. 

PMID- 24038261
TI  - Public-private partnerships: the evolving role of industry funding in nutrition
      research.
AB  - The global burdens of morbidity and mortality associated with obesity-related
      chronic diseases are crippling public health and are predicted to exponentially
      increase over the next 3 decades. Meanwhile, the resources necessary to conduct
      research that may offer solutions to the obesity epidemic continue to decline and
      funding has become increasingly difficult to secure. Alternative models for
      funding nutrition and health research are necessary to make considerable and
      timely progress to improve public health. Key stakeholders include, but are not
      limited to, government agencies, foundations, private industry, and
      nongovernmental organizations. 

PMID- 24038262
TI  - Food and Nutrition Board update: What do SNAP allotments, physical fitness, and
      obesity prevention have in common?
AB  - The Institute of Medicine's Food and Nutrition Board had a productive year, with
      important expert committee reports on the Supplemental Food Assistance Program,
      physical fitness, and accelerating obesity prevention efforts that provided
      grounding for dietary guidance and nutrition policies and programs. This summary
      describes Food and Nutrition Board activities, including current thinking on
      dietary reference intakes. The summary also highlights consensus reports on
      defining and measuring Supplemental Food Assistance Program benefit adequacy and
      on physical fitness and health outcomes in youth. In addition, current and new
      activities related to obesity prevention and care are addressed. What do these
      activities have in common? All adhere to the Institute of Medicine report model
      by filling gaps and by being analytical, evidence-based, and challenging. 

PMID- 24038263
TI  - Flavonoids.

PMID- 24038264
TI  - Nutrition research to affect food and a healthy lifespan.
AB  - Proper nutrition offers one of the most effective and least costly ways to
      decrease the burden of many diseases and their associated risk factors, including
      obesity. Nutrition research holds the key to increasing our understanding of the
      causes of obesity and its related comorbidities and thus holds promise to
      markedly influence global health and economies. After outreach to 75 thought
      leaders, the American Society for Nutrition (ASN) convened a Working Group to
      identify the nutrition research needs whose advancement will have the greatest
      projected impact on the future health and well-being of global populations. ASN's
      Nutrition Research Needs focus on the following high priority areas: 1)
      variability in individual responses to diet and foods; 2) healthy growth,
      development, and reproduction; 3) health maintenance; 4) medical management; 5)
      nutrition-related behaviors; and 6) food supply/environment. ASN hopes the
      Nutrition Research Needs will prompt collaboration among scientists across all
      disciplines to advance this challenging research agenda given the high potential
      for translation and impact on public health. Furthermore, ASN hopes the findings
      from the Nutrition Research Needs will stimulate the development and adoption of
      new and innovative strategies that can be applied toward the prevention and
      treatment of nutrition-related diseases. The multidisciplinary nature of
      nutrition research requires stakeholders with differing areas of expertise to
      collaborate on multifaceted approaches to establish the evidence-based nutrition
      guidance and policies that will lead to better health for the global population.
      In addition to the identified research needs, ASN also identified 5 tools that
      are critical to the advancement of the Nutrition Research Needs: 1) omics, 2)
      bioinformatics, 3) databases, 4) biomarkers, and 5) cost-effectiveness analysis. 

PMID- 24038267
TI  - Study highlights differences in animal and human Salmonella populations.

PMID- 24038269
TI  - Wildlife: surgery gives cygnet a second chance.

PMID- 24038268
TI  - Veterinary medicines: VMD updates its guidance on advertising veterinary
      medicines.

PMID- 24038272
TI  - Vaccination guidelines group completes fact-finding visits to Asia.

PMID- 24038275
TI  - Networking to the fore at education symposium in Dublin.

PMID- 24038274
TI  - Research offers hope of new treatments for barber pole worm.

PMID- 24038276
TI  - Surveillance: pointing the way to improved welfare for companion animals.
AB  - In May this year, the VetCompass small animal surveillance project passed a
      notable milestone and celebrated the half-millionth animal being added to its
      database. To date, 190 veterinary practices across the UK have shared data on
      2,890,973 episodes of clinical care covering 502,712 animals, including 251,771
      dogs and 201,802 cats as well as a wide range of other companion animal species.
      Dan O'Neill describes the project and explains how the data gathered are being
      used. 

PMID- 24038277
TI  - African swine fever virus: on the move and dangerous.

PMID- 24038278
TI  - Clipping rabbits' teeth.

PMID- 24038279
TI  - Neurological deficits caused by tissue hypoxia in neuroinflammatory disease.
AB  - OBJECTIVE: To explore the presence and consequences of tissue hypoxia in
      experimental autoimmune encephalomyelitis (EAE), an animal model of multiple
      sclerosis (MS). METHODS: EAE was induced in Dark Agouti rats by immunization with
      recombinant myelin oligodendrocyte glycoprotein and adjuvant. Tissue hypoxia was
      assessed in vivo using 2 independent methods: an immunohistochemical probe
      administered intravenously, and insertion of a physical, oxygen-sensitive probe
      into the spinal cord. Indirect markers of tissue hypoxia (eg, expression of
      hypoxia-inducible factor-1alpha [HIF-1alpha], vessel diameter, and number of
      vessels) were also assessed. The effects of brief (1 hour) and continued (7 days)
      normobaric oxygen treatment on function were evaluated in conjunction with other
      treatments, namely administration of a mitochondrially targeted antioxidant
      (MitoQ) and inhibition of inducible nitric oxide synthase (1400W). RESULTS:
      Observed neurological deficits were quantitatively, temporally, and spatially
      correlated with spinal white and gray matter hypoxia. The tissue expression of
      HIF-1alpha also correlated with loss of function. Spinal microvessels became
      enlarged during the hypoxic period, and their number increased at relapse.
      Notably, oxygen administration significantly restored function within 1 hour,
      with improvement persisting at least 1 week with continuous oxygen treatment.
      MitoQ and 1400W also caused a small but significant improvement. INTERPRETATION:
      We present chemical, physical, immunohistochemical, and therapeutic evidence that
      functional deficits caused by neuroinflammation can arise from tissue hypoxia,
      consistent with an energy crisis in inflamed central nervous system tissue. The
      neurological deficit was closely correlated with spinal white and gray matter
      hypoxia. This realization may indicate new avenues for therapy of
      neuroinflammatory diseases such as MS.

PMID- 24038280
TI  - Assembling a phthalocyanine and perylenediimide donor-acceptor hybrid through a
      platinum(II) diacetylide linker.
AB  - In a novel electron-donor-acceptor conjugate, phthalocyanine (Pc) and
      perylenediimide (PDI) are connected through a trans-platinum(II) diacetylide
      linker to yield Pc-Pt-PDI 1. In the ground state, the presence of Pt(II) disrupts
      the electronic communication between the two electroactive components, as
      revealed by UV/Vis spectroscopy and electrochemical studies. The photophysical
      behavior of 1 is compared with that of the corresponding Pc-PDI electron-donor
      acceptor conjugate 2 in terms of charge separation and charge recombination. The
      insertion of Pt(II) between Pc and PDI impacts the results in a longer-lived
      Pc(.) (+) /PDI(.) (-) radical ion-pair state. In addition, the intermediately
      formed Pc triplet excited state is formed with higher quantum yields in 1 than in
      2. 

PMID- 24038281
TI  - Ultrabright organic dots with aggregation-induced emission characteristics for
      real-time two-photon intravital vasculature imaging.
AB  - Ultrabright organic dots with aggregation-induced emission characteristics (AIE
      dots) are prepared and shown to exhibit a high quantum yield, a, large two-photon
      absorption cross-section, and low in vivo toxicity. Real-time two-photon
      intravital blood vascular imaging in various tissues substantiates that the AIE
      dots are effective probes for in vivo vasculature imaging in a deep and high
      contrast manner. 

PMID- 24038282
TI  - Diffusion-weighted MRI monitoring of pancreatic cancer response to radiofrequency
      heat-enhanced intratumor chemotherapy.
AB  - The aim of this study was to evaluate the feasibility of using diffusion-weighted
      MRI to monitor the early response of pancreatic cancers to radiofrequency heat
      (RFH)-enhanced chemotherapy. Human pancreatic carcinoma cells (PANC-1) in
      different groups and 24 mice with pancreatic cancer xenografts in four groups
      were treated with phosphate-buffered saline (PBS) as a control, RFH at 42 
      degrees C, gemcitabine and gemcitabine plus RFH at 42  degrees C. One day before
      and 1, 7 and 14 days after treatment, diffusion-weighted MRI and T2 -weighted
      imaging were applied to monitor the apparent diffusion coefficients (ADCs) of
      tumors and tumor growth. MRI findings were correlated with the results of tumor
      apoptosis analysis. In the in vitro experiments, the quantitative viability assay
      showed lower relative cell viabilities for treatment with gemcitabine plus RFH at
      42  degrees C relative to treatment with RFH only and gemcitabine only (37 +/- 5%
      versus 65 +/- 4% and 58 +/- 8%, respectively, p < 0.05). In the in vivo
      experiments, the combination therapy resulted in smaller relative tumor volumes
      than RFH only and chemotherapy only (0.82 +/- 0.17 versus 2.23 +/- 0.90 and 1.64
      +/- 0.44, respectively, p = 0.003). In vivo, 14-T MRI demonstrated a remarkable
      decrease in ADCs at day 1 and increased ADCs at days 7 and 14 in the combination
      therapy group. The apoptosis index in the combination therapy group was
      significantly higher than those in the chemotherapy-only, RFH-only and PBS
      treatment groups (37 +/- 6% versus 20 +/- 5%, 8 +/- 2% and 3 +/- 1%,
      respectively, p < 0.05). This study confirms that it is feasible to use MRI to
      monitor RFH-enhanced chemotherapy in pancreatic cancers, which may present new
      options for the efficient treatment of pancreatic malignancies using MRI/RFH
      integrated local chemotherapy.

PMID- 24038284
TI  - Self-controlled case series method with smooth age effect.
AB  - The self-controlled case series method, commonly used to investigate potential
      associations between vaccines and adverse events, requires information on cases
      only and automatically controls all age-independent multiplicative confounders
      while allowing for an age-dependent baseline incidence. In the parametric version
      of the method, we modelled the age-specific relative incidence by using a
      piecewise constant function, whereas in the semiparametric version, we left it
      unspecified. However, mis-specification of age groups in the parametric version
      can lead to biassed estimates of exposure effect, and the semiparametric approach
      runs into computational problems when the number of cases in the study is
      moderately large. We, thus, propose to use a penalized likelihood approach where
      the age effect is modelled using splines. We use a linear combination of cubic M
      splines to approximate the age-specific relative incidence and integrated splines
      for the cumulative relative incidence. We conducted a simulation study to
      evaluate the performance of the new approach and its efficiency relative to the
      parametric and semiparametric approaches. Results show that the new approach
      performs equivalently to the existing methods when the sample size is small and
      works well for large data sets. We applied the new spline-based approach to data
      on febrile convulsions and paediatric vaccines. Co

PMID- 24038283
TI  - MADD is a downstream target of PTEN in triggering apoptosis.
AB  - Mitogen-activated kinase activating death domain containing protein (MADD) is
      abundantly expressed in cancer cells and necessary for maintaining cancer cell
      survival. However, this survival function of MADD is dependent upon its
      phosphorylation by protein kinase B (Akt). The tumour suppressor PTEN
      (phosphatase and tensin homolog deleted on chromosome 10) is a lipid phosphatase
      that negatively regulates the phosphatidylinositol 3-kinase (PI3K)-Akt signaling
      pathway. The downstream targets of PTEN in triggering apoptosis have not yet been
      completely identified. Here, we report that MADD can act as a pro-apoptotic
      factor to initiate TRAIL-induced apoptosis when its phosphorylation is attenuated
      by PTEN. Our data show that tumor necrosis factor alpha-related apoptosis
      inducing ligand (TRAIL) induced a reduction in MADD phosphorylation with a
      concomitant up-regulation of PTEN. Knock down of PTEN using a specific siRNA
      prevented TRAIL-induced reduction in pMADD levels. Surprisingly, Akt non
      phosphorylated MADD translocated from the plasma membrane to cytoplasm where it
      bound to 14-3-3 and displaced 14-3-3 associated Bax, which translocated to
      mitochondria resulting in cytochrome c release. Taken together, our data reveal
      that PTEN can convey the death signal by preventing MADD phosphorylation by Akt.

PMID- 24038285
TI  - Studies on the enantiomers of RC-33 as neuroprotective agents: isolation,
      configurational assignment, and preliminary biological profile.
AB  - In this study we addressed the role of chirality in the biological activity of RC
      33, recently studied by us in its racemic form. An asymmetric synthesis procedure
      was the first experiment, leading to the desired enantioenriched RC-33 but with
      an enantiomeric excess (ee) not good enough for supporting the in vitro
      investigation. An enantioselective high-performance liquid chromatography (HPLC)
      procedure was then successfully carried out, yielding both RC-33 enantiomers in
      amounts and optical purity suitable for the pharmacological study. The absolute
      configuration of pure enantiomers was easily assigned exploiting the asymmetric
      synthesis previously devised. As emerged in the preliminary in vitro biological
      investigation, (S)- and (R)-RC-33 possess a comparable affinity towards the
      sigma1 receptor and a very a similar behavior in the calcium influx assay,
      resulting in an equally effective sigma1 receptor agonist. Overall, the results
      obtained so far suggest that the interaction with the biological target is
      nonstereoselective and leads us to hypothesize that there is a lack of
      stereoselectivity in the biological activity of RC-33.

PMID- 24038286
TI  - Inflammatory abdominal aortic aneurysm: a persistent painful hip.
AB  - The presentation of an abdominal aortic aneurysm (AAA) with isolated hip pain is
      a rare phenomenon. We present an atypical case of a 58-year-old previously fit
      man who presented with a 6-month history of progressively worsening left hip pain
      associated with unintentional weight loss, tender bilateral testicular swellings
      and a large non-tender palpable mass on abdominal examination. Urgent abdominal
      CT scan findings revealed a 15 cm infrarenal abdominal aortic aneurysm extending
      to the aortic bifurcation associated with an extensive left hydronephrosis. In
      theatre, the diagnosis of inflammatory AAA (IAAA) was confirmed following the
      presence of pyuria and a successful repair with an open approach using a
      bifurcated dacron graft was performed. 

PMID- 24038287
TI  - Secondary atlanto-odontoid osteoarthritis with osteoradionecrosis of upper
      cervical spine mimicking metastasis.
AB  - Osteoradionecrosis (ORN) is a known entity in patients with head and neck
      malignancy treated by radiotherapy. Involvement of mandible (0.8-37%) and maxilla
      (2-11%) is quiet common but upper cervical spine involvement is rare. One needs
      to have a high index of suspicion for the diagnosis of ORN after radiotherapy in
      the head and neck region. It may mimic either metastasis or an infection and
      needs histopathology to make definitive diagnosis. We reported the successful
      treatment of a patient with ORN involving upper cervical spine by posterior
      decompression and stabilisation. In addition, a new technique of reaching the
      odontoid process from posterior aspect for biopsy has been described. 

PMID- 24038288
TI  - Wearable cardioverter defibrillator in stress cardiomyopathy and cardiac arrest.
AB  - A 57-year-old woman presented with nausea, vomiting and diarrhoea. She had severe
      hypokalaemia and hypomagnesemia with marked QTc (680 ms) prolongation after
      suspected viral diarrhoea. She then developed progressive dyspnoea with
      congestion. An echocardiogram was obtained and showed severe hypokinesis with
      apical ballooning and hyperdynamic cardiac base, suggestive of stress
      cardiomyopathy. A repeat ECG showed further prolongation of the QTc (883 ms) and
      she rapidly developed polymorphic ventricular tachycardia. She underwent cardiac
      arrest and was successfully resuscitated. A coronary angiogram confirmed the
      diagnosis of stress cardiomyopathy. We had therapeutic dilemma at discharge to
      implant a permanent automated implantable cardiac defibrillator in view of the
      high risk for recurrent ventricular tachycardia, or follow-up for resolution of
      both reversible causes of the prolonged QTc (stress cardiomyopathy and
      electrolytes abnormalities). We suggested an alternate treatment for sudden death
      prevention in high risk patients who have reversible cause for QT interval
      prolongation. 

PMID- 24038289
TI  - Corticosteroid treatment buys time in case of a newly diagnosed hypophysitis with
      visual deterioration.
AB  - Hypophysitis is an important differential diagnosis for a pituitary mass,
      especially in young women at the end of or shortly after pregnancy. It commonly
      results in hypopituitarism and can be differentiated from adenoma on MRI. Typical
      MRI characteristics of hypophysitis are symmetry, loss of posterior bright spot,
      intense and homogeneous gadolinium enhancement, a thickened pituitary stalk and
      intact sellar floor. Treatment of choice in the acute phase of a hypophysitis is
      corticosteroids. Adequate corticosteroid treatment may effectively buy time and
      avoid unnecessary surgical treatment and is related to further decrease of
      pituitary function, even in progressive cases of deterioration due to compression
      of the chiasm. Strict monitoring of the vision and a control MRI is obligatory to
      evaluate the treatment after 48-36 h. Tissue diagnosis is mandatory when there
      are multiple relapses. We present a case of progressive visual deterioration in
      hypophysitis, successfully treated with high-pulse dose prednisolone. 

PMID- 24038290
TI  - Mature teratoma of the thymus.
AB  - A 55-year-old man presented with a 7-month history of an intermittent dry cough
      after returning from Turkey. A chest radiograph revealed a large mass-like
      opacity in the right lung field and CT demonstrated a 13 cm round, cystic lesion
      in the anterior mediastinum. The patient was referred to the cardiothoracic
      surgical team for rigid bronchoscopy, thoracotomy and resection. Surgery was
      uncomplicated with a rapid uneventful recovery. Histology concluded a diagnosis
      of a mature teratoma of the thymus. 

PMID- 24038291
TI  - Toxic epitheliopathy from a single application of preservative free oxybuprocaine
      (0.4%) in a patient with Sjogren's syndrome.
AB  - Topical ocular anaesthetic agents are frequently used for ophthalmic diagnosis
      and surgery. While corneal complications following long-term use or misuse of
      local anaesthetic solutions have been described, toxic epitheliopathy after a
      single application of six drops of preservative free oxybuprocaine is rare. In
      order to increase the awareness of this ocular complication, we report such a
      case in a patient with Sjogren's syndrome who presented for elective cataract
      surgery. We outline the mechanisms proposed to explain the ocular toxic effects
      of oxybuprocaine and discuss the management principles in preventing this
      complication in the context of Sjogren's syndrome. 

PMID- 24038292
TI  - Bilateral striopallidodentate calcinosis secondary to postsurgical
      hypoparathyroidism.

PMID- 24038293
TI  - Black urine after medicinal foot baths.

PMID- 24038294
TI  - 'Monod' and 'air crescent' sign in aspergilloma.

PMID- 24038295
TI  - Atypical blood and bone marrow lymphocytes in ALK-positive anaplastic T-cell
      lymphoma: important lessons.
AB  - A 42-year-old man presented with a short history of fever, significant weight
      loss and bilateral neck swelling. A CT scan revealed widespread lymphadenopathy
      and hepatosplenomegaly. Lymph node morphology and immunohistochemistry confirmed
      a diagnosis of anaplastic lymphoma kinase (ALK)-positive anaplastic T-cell non
      Hodgkin's lymphoma. Both the peripheral blood (PB) and bone marrow (BM) revealed
      atypical lymphocytes with cleaved nuclei, vacuolation and granulation, suggestive
      of disease involvement at both sites. However, BM and PB immunophenotyping and
      immunohistochemistry did not reveal typical markers (ALK and CD30) at either
      site. All features resolved with a short remission after conventional
      chemotherapy. Despite salvage chemotherapy and an autologous stem cell
      transplant, a relapse of the PB and BM features with stable radiological findings
      was noted. Rapid decline followed with pancytopenia resulting in death 12 months
      after the initial diagnosis. 

PMID- 24038296
TI  - Lung cancer underlying paravertebral abscess with intramedullary spinal cord
      metastases.

PMID- 24038297
TI  - Ring-enhancing pontine lesion in a young boy.

PMID- 24038298
TI  - The effect of low- and high-velocity tendon excursion on the mechanical
      properties of human cadaver subsynovial connective tissue.
AB  - Fibrosis of the subsynovial connective tissue (SSCT) in the carpal tunnel is the
      most common histological finding in carpal tunnel syndrome (CTS). Fibrosis may
      result from damaged SSCT. Previous studies found that with low-velocity (2 mm/s),
      tendon excursions can irreversibly damage the SSCT. We investigated the effect of
      tendon excursion velocity in the generation of SSCT damage. Nine human cadaver
      wrists were used. Three repeated cycles of ramp-stretch testing were performed
      simulating 40%, 60%, 90%, and 120% of the middle finger flexor tendon
      superficialis physiological excursion with an excursion velocity of 60 mm/s.
      Energy and force were calculated and normalized by values obtained in the first
      cycle for each excursion level. Data were compared with low-velocity excursion
      data. For high-velocity excursions, a significant drop in the excursion energy
      ratio was first observed at an excursion level of 60% physiological excursion (p
      < 0.024) and that for low-velocity excursions was first observed at 90%
      physiological excursion (p < 0.038). Furthermore, the energy ratio was lower at
      60% for high velocities (p <= 0.039). Increasing velocity lowers the SSCT damage
      threshold. This finding may be relevant for understanding the pathogenesis of
      SSCT fibrosis, such as that accompanying CTS, and a relationship with
      occupational factors.

PMID- 24038299
TI  - Evidence of male-biased dispersal in the endangered Sichuan snub-nosed monkey
      (Rhinopithexus roxellana).
AB  - Although sex-biased dispersal has profound effects on the viability of small and
      isolated populations resulting from habitat change and anthropogenic disturbance,
      the direction and strength of sex-biased dispersal in the endangered Sichuan snub
      nosed monkey (Rhinopithexus roxellana) remains poorly understood. Here, we
      investigated dispersal patterns of R. roxellana using 15 polymorphic
      microsatellite loci. Using noninvasive methods we obtained 337 fecal samples from
      individuals residing in four multilevel troops that inhabit the Shennongjia
      Nature Reserve (SNR). Our study site contains an isolated population of
      approximately 1,000 Sichuan snub-nosed monkeys located in the easternmost
      distribution of the species' range. Our results indicated that the mean
      coefficient of relatedness among troop members was low (mean relatedness +/- SE =
      0.038 +/- 0.025). However, the mean relatedness of monkeys residing in the same
      troop was significantly higher than the mean relatedness of monkeys belonging to
      different troops, suggesting that some members of the same troop were closely
      relatived. Sex-biased dispersal tests revealed that dispersal in R. roxellana was
      male-biased. Moreover, analysis of isolation-by-distance indicated that the
      correlation between pairwise genetic distance and geographical distance was
      positive for females, while it was negative for males. These data suggest that
      males tended to disperse further than females, although these values were not
      statistically significant. Considering previous field data collected on Sichuan
      snub-nosed monkeys from other sites, we suggest that mating competition among
      males and female mate choice represent the major causes of male-biased dispersal
      in R. roxellana.

PMID- 24038300
TI  - Synthesis, characterization, and reactivity of cobalt(III)-oxygen complexes
      bearing a macrocyclic N-tetramethylated cyclam ligand.
AB  - Mononuclear metal-dioxygen species are key intermediates that are frequently
      observed in the catalytic cycles of dioxygen activation by metalloenzymes and
      their biomimetic compounds. In this work, a side-on cobalt(III)-peroxo complex
      bearing a macrocyclic N-tetramethylated cyclam (TMC) ligand, [Co(III) (15-TMC)(O2
      )](+) , was synthesized and characterized with various spectroscopic methods.
      Upon protonation, this cobalt(III)-peroxo complex was cleanly converted into an
      end-on cobalt(III)-hydroperoxo complex, [Co(III) (15-TMC)(OOH)](2+) . The
      cobalt(III)-hydroperoxo complex was further converted to [Co(III) (15-TMC-CH2 
      O)](2+) by hydroxylation of a methyl group of the 15-TMC ligand. Kinetic studies
      and (18) O-labeling experiments proposed that the aliphatic hydroxylation
      occurred via a Co(IV) -oxo (or Co(III) -oxyl) species, which was formed by O?O
      bond homolysis of the cobalt(III)-hydroperoxo complex. In conclusion, we have
      shown the synthesis, structural and spectroscopic characterization, and
      reactivities of mononuclear cobalt complexes with peroxo, hydroperoxo, and oxo
      ligands. 

PMID- 24038301
TI  - The structure of the Montgomery-Asberg depression rating scale over the course of
      treatment for depression.
AB  - The Montgomery-Asberg Depression Rating Scale (MADRS) is a widely used clinician
      rated measure of depressive severity. Empirical support for the factor structure
      of the MADRS is mixed; further, the comparison of MADRS scores within and between
      patients requires the demonstration of consistent instrument properties. The
      objective of the current investigation was to evaluate MADRS factor structure as
      well as MADRS factorial invariance across time and gender. The MADRS was
      administered to 821 depressed outpatients participating in a large-scale
      effectiveness study of combined pharmacotherapy and psychotherapy for depression.
      Treatment outcome did not differ across treatment groups. Factor structure and
      invariance was evaluated via confirmatory factor analysis. A four-factor model
      consisting of Sadness, Negative Thoughts, Detachment and Neurovegetative symptoms
      demonstrated a good fit to the data. This four-factor structure was invariant
      across time and gender. A hierarchical model, in which these four factors served
      as indicators of a general depression factor, was also supported. A limitation of
      the current study is the lack of comprehensive characterization of patient
      clinical features; results need to be replicated in more severely depressed or
      treatment refractory patients. Overall, evidence supported the use of the MADRS
      total score as well as subscales focused on affective, cognitive, social and
      somatic aspects of depression in male and female outpatients.

PMID- 24038302
TI  - Subcomponent self-assembly: a quick way to new metallogels.
AB  - 1-2-3 gel! Subcomponent self-assembly is introduced as a new design route towards
      multistimuli-responsive metallogels. It offers a rapid and facile access to
      supramolecular gels and allows to design smart materials with diverse functional
      and structural properties by simply exchanging one (or more) of the components.
      Herein, the exchange of the metal ions is emphasized (see scheme).

PMID- 24038304
TI  - Re: Elliott CS, Comiter CV. The effect of angiotensin inhibition on urinary
      incontinence: data from the National Health and Nutrition Examination Survey
      (2001-2008). Neurourol urodyn 2014; 33:1178-81.

PMID- 24038303
TI  - Associations of objectively measured and self-reported sleep duration with
      carotid artery intima media thickness among police officers.
AB  - BACKGROUND: We aimed to examine the association of objectively measured and self
      reported sleep duration with carotid artery intima media thickness (IMT) among
      257 police officers, a group at high risk for cardiovascular disease (CVD).
      METHODS: Sleep duration was estimated using actigraphic data and through self
      reports. The mean maximum IMT was the average of the largest 12 values scanned
      bilaterally from three angles of the near and far wall of the common carotid,
      bulb, and internal carotid artery. Linear and quadratic regression models were
      used to assess the association of sleep duration with IMT. RESULTS: Officers who
      had fewer than 5 or 8 hr or more of objectively measured sleep duration had
      significantly higher maximum IMT values, independent of age. Self-reported sleep
      duration was not associated with either IMT measure. CONCLUSION: Attainment of
      sufficient sleep duration may be considered as a possible strategy for
      atherosclerosis prevention among police officers.

PMID- 24038305
TI  - Increasing the open-circuit voltage in high-performance organic photovoltaic
      devices through conformational twisting of an indacenodithiophene-based
      conjugated polymer.
AB  - A fused ladder indacenodithiophene (IDT)-based donor-acceptor (D-A)-type
      alternating conjugated polymer, PIDTHT-BT, presenting n-hexylthiophene conjugated
      side chains is prepared. By extending the degree of intramolecular repulsion
      through the conjugated side chain moieties, an energy level for the highest
      occupied molecular orbital (HOMO) of -5.46 eV--a value approximately 0.27 eV
      lower than that of its counterpart PIDTDT-BT--is obtained, subsequently providing
      a fabricated solar cell with a high open-circuit voltage of approximately 0.947
      V. The hole mobility (determined using the space charge-limited current model) in
      a blend film containing 20 wt% PIDTHT-BT) and 80 wt% [6,6]-phenyl-C71 butyric
      acid methyl ester (PC71 BM) is 2.2 * 10(-9) m(2) V(-1) s(-1), which is within the
      range of reasonable values for applications in organic photovoltaics. The power
      conversion efficiency is 4.5% under simulated solar illumination (AM 1.5G, 100 mW
      cm(-2)).

PMID- 24038306
TI  - A comparison of calcium to zoledronic acid for improvement of cortical bone in an
      animal model of CKD.
AB  - Patients with chronic kidney disease (CKD) have increased risk of fractures, yet
      the optimal treatment is unknown. In secondary analyses of large randomized
      trials, bisphosphonates have been shown to improve bone mineral density and
      reduce fractures. However, bisphosphonates are currently not recommended in
      patients with advanced kidney disease due to concern about oversuppressing bone
      remodeling, which may increase the risk of developing arterial calcification. In
      the present study we used a naturally occurring rat model of CKD with secondary
      hyperparathyroidism, the Cy/+ rat, and compared the efficacy of treatment with
      zoledronic acid, calcium given in water to simulate a phosphate binder, and the
      combination of calcium and zoledronic acid. Animals were treated beginning at 25
      weeks of age (approximately 30% of normal renal function) and followed for 10
      weeks. The results demonstrate that both zoledronic acid and calcium improved
      bone volume by micro-computed tomography (uCT) and both equally suppressed the
      mineral apposition rate, bone formation rate, and mineralizing surface of
      trabecular bone. In contrast, only calcium treatment with or without zoledronic
      acid improved cortical porosity and cortical biomechanical properties (ultimate
      load and stiffness) and lowered parathyroid hormone (PTH). However, only calcium
      treatment led to the adverse effects of increased arterial calcification and
      fibroblast growth factor 23 (FGF23). These results suggest zoledronic acid may
      improve trabecular bone volume in CKD in the presence of secondary
      hyperparathyroidism, but does not benefit extraskeletal calcification or cortical
      biomechanical properties. Calcium effectively reduces PTH and benefits both
      cortical and trabecular bone yet increases the degree of extra skeletal
      calcification. (c) 2014 American Society for Bone and Mineral Research. 

PMID- 24038307
TI  - ACB-PCR measurement of spontaneous and furan-induced H-ras codon 61 CAA to CTA
      and CAA to AAA mutation in B6C3F1 mouse liver.
AB  - Furan is a rodent liver carcinogen, but the mode of action for furan
      hepatocarcinogenicity is unclear. H-ras codon 61 mutations have been detected in
      spontaneous liver tumors of B6C3F1 mice, and the fraction of liver tumors
      carrying H-ras codon 61 CAA to AAA mutation increased in furan-treated mice.
      Allele-specific competitive blocker PCR (ACB-PCR) has been used previously to
      quantify early, carcinogen-induced increases in tumor-associated mutations. The
      present pilot study investigated whether furan drives clonal expansion of pre
      existing H-ras mutant cells in B6C3F1 mouse liver. H-ras codon 61 CAA to CTA and
      CAA to AAA mutations were measured in DNA isolated from liver tissue of female
      mice treated with 0, 1, 2, 4, or 8 mg furan/kg body weight, five days per week
      for three weeks, using five mice per treatment group. Spontaneous levels of
      mutation were low, with two of five control mice having an H-ras codon 61 CTA or
      AAA mutant fraction (MF) greater than 10(-5) . Several furan-treated mice had H
      ras codon 61 AAA or CTA MFs greater than those measured in control mice and lower
      bound estimates of induced MF were calculated. However, no statistically
      significant differences were observed between treatment groups. Therefore, while
      sustained exposure to furan is carcinogenic, at the early stage of carcinogenesis
      examined in this study (three weeks), there was not a significant expansion of H
      ras mutant cells.

PMID- 24038308
TI  - Determination of the appropriate b value and number of gradient directions for
      high-angular-resolution diffusion-weighted imaging.
AB  - High-angular-resolution diffusion-weighted imaging (HARDI) is one of the most
      common MRI acquisition schemes for use with higher order models of diffusion.
      However, the optimal b value and number of diffusion-weighted (DW) directions for
      HARDI are still undetermined, primarily as a result of the large number of
      available reconstruction methods and corresponding parameters, making it
      impossible to identify a single criterion by which to assess performance. In this
      study, we estimate the minimum number of DW directions and optimal b values
      required for HARDI by focusing on the angular frequency content of the DW signal
      itself. The spherical harmonic (SH) series provides the spherical analogue of the
      Fourier series, and can hence be used to examine the angular frequency content of
      the DW signal. Using high-quality data acquired along 500 directions over a range
      of b values, we estimate that SH terms above l = 8 are negligible in practice for
      b values up to 5000 s/mm(2), implying that a minimum of 45 DW directions is
      sufficient to fully characterise the DW signal. l > 0 SH terms were found to
      increase as a function of b value, levelling off at b = 3000 s/mm(2), suggesting
      that this value already provides the highest achievable angular resolution. In
      practice, it is recommended to acquire more than the minimum of 45 DW directions
      to avoid issues with imperfections in the uniformity of the DW gradient
      directions and to meet signal-to-noise requirements of the intended
      reconstruction method.

PMID- 24038309
TI  - 25th anniversary article: reversible and adaptive functional supramolecular
      materials: "noncovalent interaction" matters.
AB  - Supramolecular materials held together by noncovalent interactions, such as
      hydrogen bonding, host-guest interactions, and electrostatic interactions, have
      great potential in material science. The unique reversibility and adaptivity of
      noncovalent intreractions have brought about fascinating new functions that are
      not available by their covalent counterparts and have greatly enriched the realm
      of functional materials. This review article aims to highlight the very recent
      and important progresses in the area of functional supramoleuclar materials,
      focusing on adaptive mechanical materials, smart sensors with enhanced
      selectivity, soft luminescent and electronic nanomaterials, and biomimetic and
      biomedical materials with tailored structures and functions. We cannot write a
      complete account of all the interesting work in this area in one article, but we
      hope that it can in a way reflect the current situation and future trends in this
      prosperously developing area of functional supramolecular materials. 

PMID- 24038310
TI  - An amino-acid-based self-healing hydrogel: modulation of the self-healing
      properties by incorporating carbon-based nanomaterials.
AB  - An amino-acid-based (11-(4-(pyrene-1-yl)butanamido)undecanoic acid) self
      repairing hydrogel is reported. The native hydrogel, as well as hybrid hydrogels,
      have been thoroughly characterized by using various microscopic techniques,
      including transmission electron microscopy (TEM), atomic force microscopy (AFM),
      Raman spectroscopy, fluorescence spectroscopy, FTIR spectroscopy, X-ray
      diffraction, and by using rheological experiments. The native hydrogel exhibited
      interesting fluorescence properties, as well as a self-healing property.
      Interestingly, the self-healing, thixotropy, and stiffness of the native hydrogel
      can be successfully modulated by incorporating carbon-based nanomaterials,
      including graphene, pristine single-walled carbon nanotubes (Pr-SWCNTs), and both
      graphene and Pr-SWCNTs, within the native gel system. The self-recovery time of
      the gel was shortened by the inclusion of reduced graphene oxide (RGO), Pr
      SWCNTs, or both RGO and Pr-SWCNTs. Moreover, hybrid gels that contained RGO
      and/or Pr-SWCNTs exhibited interesting semiconducting behavior. 

PMID- 24038311
TI  - Human Wharton's jelly stem cells and its conditioned medium enhance healing of
      excisional and diabetic wounds.
AB  - Wound healing is a major problem in diabetic patients and current treatments have
      met with limited success. We evaluated the treatment of excisional and diabetic
      wounds using a stem cell isolated from the human umbilical cord Wharton's jelly
      (hWJSC) that shares unique properties with embryonic and adult mesenchymal stem
      cells. hWJSCs are non-controversial, available in abundance, hypo-immunogenic,
      non-tumorigenic, differentiate into keratinocytes, and secrete important
      molecules for tissue repair. When human skin fibroblasts (CCD) in conventional
      scratch-wound assays were exposed to hWJSC-conditioned medium (hWJSC-CM) the
      fibroblasts at the wound edges migrated and completely covered the spaces by day
      2 compared to controls. The number of invaded cells, cell viability, total
      collagen, elastin, and fibronectin levels were significantly greater in the hWJSC
      CM treatment arm compared to controls (P < 0.05). When a single application of
      green fluorescent protein (GFP)-labeled hWJSCs (GFP-hWJSCs) or hWJSC-CM was
      administered to full-thickness murine excisional and diabetic wounds, healing
      rates were significantly greater compared to controls (P < 0.05). Wound biopsies
      collected at various time points showed the presence of green GFP-labeled hWJSCs,
      positive human keratinocyte markers (cytokeratin, involucrin, filaggrin) and
      expression of ICAM-1, TIMP-1, and VEGF-A. On histology, the GFP-hWJSCs and hWJSC
      CM treated wounds showed reepithelialization, increased vascularity and cellular
      density and increased sebaceous gland and hair follicle numbers compared to
      controls. hWJSCs showed increased expression of several miRNAs associated with
      wound healing compared to CCDs. Our studies demonstrated that hWJSCs enhance
      healing of excisional and diabetic wounds via differentiation into keratinocytes
      and release of important molecules.

PMID- 24038312
TI  - Facile synthesis and enhanced nonlinear optical properties of porphyrin
      functionalized multi-walled carbon nanotubes.
AB  - Two multi-walled carbon nanotube (MWCNT)-based nanohybrids, MWCNT-ZnTPP and MWCNT
      TPP (TPP=5-[4-{2-(4-formylphenoxy)- ethyloxy}phenyl]-10,15,20-triphenylporphyrin,
      ZnTPP=5-[4-{(4-formylphenyl)ethynyl}phenyl]-10,15,20
      triphenylporphinatozinc(II)), were prepared directly from pristine MWCNTs through
      1,3-dipolar cycloaddition reactions. Covalent attachment of the porphyrins to the
      surfaces of the MWCNTs was confirmed by Fourier transform infrared spectroscopy,
      ultraviolet/visible absorption, fluorescence, Raman, and X-ray photoelectron
      spectroscopy, elemental analysis, transmission electron microscopy, and
      thermogravimetric analysis. Attachment of the porphyrin moieties to the surface
      of the MWCNTs significantly improves the solubility and ease of processing of
      these MWCNT-porphyrin composite materials. Z-scan studies reveal that these MWCNT
      porphyrin nanohybrids exhibit enhanced nonlinear optical properties under both
      nanosecond and picosecond laser pulses at lambda=532 nm in comparison with free
      MWCNTs and the free porphyrin chromophores, whereas superior optical limiting
      performance was displayed by MWCNT-porphyrin composite materials rather than
      MWCNTs/ZnTPP and MWCNTs/TPP blends, which is consistent with a remarkable
      accumulation effect as a result of the covalent linkage between the porphyrin and
      the MWCNTs. 

PMID- 24038313
TI  - Patterns of movement and seed dispersal by three lemur species.
AB  - We combined data on gut-passage times, feeding, and movement to explore the
      patterns of seed dispersal by Eulemur rubriventer, Eulemur rufrifrons, and
      Varecia variegata editorum lemurs in Ranomafana National Park, Madagascar. These
      lemur species deposited less than half of their consumed seeds >100 m away from
      conspecific trees (40-50%). Long-distance dispersal (>500 m) was rare and average
      dispersal distances were short relative to those reported of similar-sized
      haplorrhine primates. The three lemur species showed no significant differences
      in mean seed-dispersal distances. However, they differed in the shape of their
      frequency distributions of seed-dispersal distances as a result of differences in
      how they moved through their habitats. The short distances of seed dispersal we
      observed and the depauperate frugivorous fauna in Madagascar suggest seed
      dispersal may be more limited than in other tropical forests with important
      implications for plant-community dynamics, biodiversity maintenance, and
      restoration efforts in Madagascar.

PMID- 24038314
TI  - Cardiac imaging at 7 Tesla: Single- and two-spoke radiofrequency pulse design
      with 16-channel parallel excitation.
AB  - PURPOSE: Higher signal to noise ratio (SNR) and improved contrast have been
      demonstrated at ultra-high magnetic fields (>=7 Tesla [T]) in multiple targets,
      often with multi-channel transmit methods to address the deleterious impact on
      tissue contrast due to spatial variations in B1 (+) profiles. When imaging the
      heart at 7T, however, respiratory and cardiac motion, as well as B0
      inhomogeneity, greatly increase the methodological challenge. In this study we
      compare two-spoke parallel transmit (pTX) RF pulses with static B1 (+) shimming
      in cardiac imaging at 7T. METHODS: Using a 16-channel pTX system, slice-selective
      two-spoke pTX pulses and static B1 (+) shimming were applied in cardiac CINE
      imaging. B1 (+) and B0 mapping required modified cardiac triggered sequences.
      Excitation homogeneity and RF energy were compared in different imaging
      orientations. RESULTS: Two-spoke pulses provide higher excitation homogeneity
      than B1 (+) shimming, especially in the more challenging posterior region of the
      heart. The peak value of channel-wise RF energy was reduced, allowing for a
      higher flip angle, hence increased tissue contrast. Image quality with two-spoke
      excitation proved to be stable throughout the entire cardiac cycle. CONCLUSION:
      Two-spoke pTX excitation has been successfully demonstrated in the human heart at
      7T, with improved image quality and reduced RF pulse energy when compared with B1
      (+) shimming.

PMID- 24038315
TI  - Core pathology of eating disorders as measured by the Eating Disorder Examination
      Questionnaire (EDE-Q): the predictive role of a nested general (g) and primary
      factors.
AB  - The present study examined several factor models of the Eating Disorder
      Examination Questionnaire (EDE-Q), and in particular, whether a nested general
      factor ('g') was present, hence supporting a common pathology factor. A total of
      1094 women were randomly selected by Statistics Norway and mailed a questionnaire
      packet. The sample was randomly split, using the first half for exploratory
      analyses and the second for confirmatory validation purposes. A four-factor
      solution received the best support, but the structure deviated from the original
      model of Fairburn. The internal consistency was high for the first three factors
      (.93, .82 and .86) and satisfactory for the fourth (.78). The additional
      specification of a general (g) factor improved model fit significantly, implying
      that the EDE-Q scores are indicators of both a general core and four primary
      symptom patterns. Furthermore, the g was more strongly related to predictors like
      age and body mass index (BMI) than the four primary factors in a full structural
      equation model. The validity of interpreting the global EDE-Q score as indicative
      of g was supported. A brief Shape and Weight Concern subscale of 11 items was
      strongly related to the g-factor, and may provide an abbreviated measure of
      overall eating disorder pathology.

PMID- 24038316
TI  - Cholesterol lowering drug may influence cellular immune response by altering MHC
      II function.
AB  - Major histocompatibility complex class II (MHC II) expressed on the surface of
      antigen-presenting cells (APCs) displays peptides to CD4+ T cells. Depletion of
      membrane cholesterol from APCs by methyl beta-cyclodextrin treatment compromises
      peptide-MHC II complex formation coupled with impaired binding of conformational
      antibody, which binds close to the peptide binding groove of MHC II.
      Interestingly, the total cell surface of MHC II remains unaltered. These defects
      can be corrected by restoring membrane cholesterol. In silico docking studies
      with a three-dimensional model showed the presence of a cholesterol binding site
      in the transmembrane domain of MHC II (TM-MHC-II). From the binding studies it
      was clear that cholesterol, indeed, interacts with the TM-MHC-II and alters its
      conformation. Mutation of cholesterol binding residues (F240, L243, and F246) in
      the TM-MHC-II decreased the affinity for cholesterol. Furthermore, transfection
      of CHO cells with full-length mutant MHC II, but not wild-type MHC II, failed to
      activate antigen-specific T cells coupled with decreased binding of conformation
      specific antibodies. Thus, cholesterol-induced conformational change of TM-MHC-II
      may allosterically modulate the peptide binding groove of MHC II leading to T
      cell activation.

PMID- 24038318
TI  - Multiple-objective response-adaptive repeated measurement designs in clinical
      trials for binary responses.
AB  - A multiple-objective allocation strategy was recently proposed for constructing
      response-adaptive repeated measurement designs for continuous responses. We
      extend the allocation strategy to constructing response-adaptive repeated
      measurement designs for binary responses. The approach with binary responses is
      quite different from the continuous case, as the information matrix is a function
      of responses, and it involves nonlinear modeling. To deal with these problems, we
      first build the design on the basis of success probabilities. Then we illustrate
      how various models can accommodate carryover effects on the basis of logits of
      response profiles as well as any correlation structure. Through computer
      simulations, we find that the allocation strategy developed for continuous
      responses also works well for binary responses. As expected, design efficiency in
      terms of mean squared error drops sharply, as more emphasis is placed on
      increasing treatment benefit than estimation precision. However, we find that it
      can successfully allocate more patients to better treatment sequences without
      sacrificing much estimation precision.

PMID- 24038319
TI  - Mechanism of copper(I)-catalyzed allylic alkylation of phosphorothioate esters:
      influence of the leaving group on alpha regioselectivity.
AB  - The mechanism of Cu(I) -catalyzed allylic alkylation and the influence of the
      leaving groups (OPiv, SPiv, Cl, SPO(OiPr)2 ; Piv: pivavloyl) on the
      regioselectivity of the reaction have been explored by using density functional
      theory (DFT). A comprehensive comparison of many possible reaction pathways shows
      that [(iPr)2 Cu](-) prefers to bind first oxidatively to the double bond of the
      allylic substrate at the anti position with respect to the leaving group, and
      this is followed by dissociation of the leaving group. If the leaving group is
      not taken into account, the reaction then undergoes an isomerization and a
      reductive elimination process to give the alpha- or gamma-selective product. If
      OPiv, SPiv, Cl, or SPO(OiPr)2 groups are present, the optimal route for the
      formation of both alpha- and gamma-substituted products changes from the stepwise
      elimination to the direct process, in which the leaving group plays a stabilizing
      role for the reactant and destabilizes the transition state. The differences to
      the energy barrier for the alpha- and gamma-substituted products are 2.75 kcal
      mol(-1) with SPO(OiPr)2 , 2.44 kcal mol(-1) with SPiv, 2.33 kcal mol(-1) with
      OPiv, and 1.98 kcal mol(-1) with Cl, respectively; these values show that alpha
      regioselectivity in the allylic alkylation follows a SPO(OiPr)2 >SPiv>OPiv>Cl
      trend, which is in satisfactory agreement with the experimental findings. This
      trend mainly originates in the differences between the attractive electrostatic
      forces and the repelling steric interactions of the SPO(OiPr)2 , SPiv, OPiv, and
      Cl groups on the Cu group.

PMID- 24038317
TI  - Structural basis for distinct functions of the naturally occurring Cys mutants of
      human apolipoprotein A-I.
AB  - HDL removes cell cholesterol and protects against atherosclerosis. ApoA-I
      provides a flexible structural scaffold and an important functional ligand on the
      HDL surface. We propose structural models for apoA-I(Milano) (R173C) and apoA
      I(Paris) (R151C) mutants that show high cardioprotection despite low HDL levels.
      Previous studies established that two apoA-I molecules encircle HDL in an
      antiparallel, helical double-belt conformation. Recently, we solved the atomic
      structure of lipid-free Delta(185-243)apoA-I and proposed a conformational
      ensemble for apoA-I(WT) on HDL. Here we modify this ensemble to understand how
      intermolecular disulfides involving C173 or C151 influence protein conformation.
      The double-belt conformations are modified by belt rotation, main-chain unhinging
      around Gly, and Pro-induced helical bending, and they are verified by comparison
      with previous experimental studies and by molecular dynamics simulations of apoA
      I(Milano) homodimer. In our models, the molecular termini repack on various-sized
      HDL, while packing around helix-5 in apoA-I(WT), helix-6 in apoA-I(Paris), or
      helix-7 in apoA-I(Milano) homodimer is largely conserved. We propose how the
      disulfide-induced constraints alter the protein conformation and facilitate
      dissociation of the C-terminal segment from HDL to recruit additional lipid. Our
      models unify previous studies of apoA-I(Milano) and demonstrate how the
      mutational effects propagate to the molecular termini, altering their
      conformations, dynamics, and function.

PMID- 24038320
TI  - Stereochemical preference of 2'-deoxycytidine for chiral bis(diamido)-bridged
      basket resorcin[4]arenes.
AB  - Bis(diamido)-bridged basket resorcin[4]arene (all-S)-1 and its (all-R)-1
      enantiomer proved able to interact with 2'-deoxycytidine (2) and pyrimidine
      nucleoside analogs in dimethyl sulfoxide (DMSO) solution. In such a solvent, the
      resorcinarene hosts adopt a preferential 1,3-alternate-like conformation, with a
      larger cavity delimited by two syn 3,5-dimethoxyphenyl moieties, and two external
      pockets, each delimited by the other 3,5-dimethoxyphenyl group and its diamido
      arm (the wing). Complexation phenomena were investigated by nuclear magnetic
      resonance (NMR) methods, including (1)H NMR DOSY and 1D ROESY experiments, and
      molecular modeling. Heteroassociation constants of [(all-S)-1.2] and [(all-R)
      1.2] diastereoisomeric complexes were obtained from diffusion data by single
      point measurements, and from nonlinear fitting of 1H NMR chemical shifts.
      Selective proton relaxation rate measurements allowed us to significantly
      discriminate the two complexes by identifying two different interaction sites of
      the guest in the resorcin[4]arene host, depending on its configuration.

PMID- 24038321
TI  - The effect of lymphatico-venous anastomosis for an intractable ulcer at the lower
      leg in a marked obese patient.
AB  - Secondary lymphedema occurs after trauma, cancer surgery, or obesity, and wounds
      in lymphedema can easily become intractable. We report positive results using
      lymphatico-venous anastomosis (LVA) to treat a post-traumatic lymph fistula and
      an intractable ulcer in a severely obese patient. A 41-year-old male (BMI 51.8),
      one year prior, had a traffic injury, and had an 18-cm contusion in his right
      leg. Six months later, lymph leakage in a 14 cm * 8 cm region and a 5 cm * 3 cm
      skin ulcer occurred in the center of the wound. We made a diagnosis of lymphedema
      resulting from obesity, accompanied with lymphorrhea and intractable ulcer. He
      was unable to reach his legs owing to obesity, making complex physical therapy
      impossible. We performed LVA under local anesthesia. The lymphorrhea healed 2
      weeks after the operation and had not recurred 3 months after the operation. The
      leg lymphedema improved after the surgery without the compression therapy. In
      cases of intractable ulcers, suspected of being caused by lymphostasis,
      treatments indicated for lymphedema, for example LVA, may possibly allow
      satisfactory wound healing. (c) 2013 Wiley Periodicals, Inc. Microsurgery 34:64
      67, 2014. 

PMID- 24038322
TI  - Hypothenar hammer syndrome: a multicenter case-control study.
AB  - BACKGROUND: The rarely diagnosed hypothenar hammer syndrome (HHS) is due to
      vascular damage to the distal part of the ulnar artery probably caused by acute
      or repetitive blunt trauma to the hypothenar region. To date, mainly case reports
      have been published, while epidemiological data are almost absent. AIM: To
      identify potential risk factors for HHS. METHOD: An interview-based multicenter
      case-control study of 71 patients with HHS and 105 matched controls was conducted
      with standardized questions regarding disease specific variables, occupation,
      exposure of the hands to different types of trauma in occupational and leisure
      context. Medical data were verified from individual medical records. RESULTS:
      Multivariable logistic regression analysis revealed that using the hand as a
      hammer on a daily basis (adjusted odds ratio [aOR] 17.04, 95% CI 5.51-52.67)
      daily pressure to the palm of the hand (aOR 4.96, 95% CI 1.39-17.71), and daily
      exposure to vibrating tools (aOR 3.41, 95% CI 1.03-11.31) were significant risk
      factors for HHS. CONCLUSIONS: This investigation represents one of the largest
      groups of patients with HHS described so far. Work-related repeated blunt trauma
      to the palm of the hand significantly increases the risk of HHS.

PMID- 24038324
TI  - Non-cardiac causes of cardiac tamponade.

PMID- 24038323
TI  - Combination of foot stimulation and tolterodine treatment eliminates bladder
      overactivity in cats.
AB  - AIMS: To determine whether transcutaneous foot stimulation combined with a lower
      dose tolterodine would inhibit bladder overactivity more effectively than either
      treatment alone. METHODS: Cystometrograms were performed on alpha-chloralose
      anesthetized cats (N = 6) by infusing 0.25% acetic acid (AA) to induce bladder
      overactivity. Foot stimulation (5 Hz) was applied at 2 and 4 times the threshold
      (T) intensity in volts (i.e., 2T or 4T) for inducing toe movement to inhibit
      bladder overactivity. Cumulative doses of tolterodine (0.003-0.3 mg/kg, i.v.)
      were also administered to determine the effect of combination treatment. RESULTS:
      AA irritation of the bladder significantly (P < 0.0001) reduced bladder capacity
      to 23.6 +/- 7.1% of saline control capacity. Foot stimulation alone at 2T and 4T
      inhibited bladder overactivity and significantly (P < 0.0001) increased bladder
      capacity to 50.7 +/- 6.8% and 79.0 +/- 11.6% of saline control, respectively.
      Tolterodine alone at 0.3 mg/kg significantly (P < 0.05) increased bladder
      capacity to 65.6 +/- 15.5% of saline control. However, when tolterodine at a
      threshold dose (0.3 mg/kg) was combined with foot stimulation, the bladder
      capacity was significantly (P < 0.05) increased to 86.2 +/- 6.2% and 107.9 +/-
      10.6% by 2T and 4T stimulation, respectively. Complete inhibition of bladder
      overactivity could be achieved at a lower tolterodine dose (0.1 mg/kg) when
      combined with 4T stimulation (97.0 +/- 11.2% of saline control). The amplitude of
      micturition contraction was not changed by tolterodine treatment. CONCLUSIONS:
      This study suggests a novel, efficacious, non-invasive therapy by combining foot
      stimulation with a lower dose tolterodine to treat bladder overactivity. It also
      provides the first objective evidence supporting an additive therapeutic benefit
      of neuromodulation and antimuscarinic combination treatment.

PMID- 24038325
TI  - Cyclization of homopropargyl chalcogenides by copper(II) salts: selective
      synthesis of 2,3-dihydroselenophenes, 3-arylselenophenes, and 3
      haloselenophenes/thiophenes.
AB  - Copper(II) halide mediated cyclization of homopropargyl chalcogenides gave three
      types of chalcogenophene derivatives. Selective product formation was achieved by
      controlling solvent, temperature, and atmosphere. By using CuBr2 and 1,2
      dichloroethane at room temperature under ambient atmosphere, 4-bromo
      dihydroselenophene derivatives were obtained, whereas CuBr2 and 1,2
      dichloroethane at reflux gave selectively 2-substituted selenophenes. When 1,2
      dichloroethane was replaced by dimethylacetamide, 3-halo-selenophenes were
      obtained exclusively. The versatility of chalcogenophenes was also studied by
      reaction of 3-haloselenophenes with terminal alkynes under Sonogashira conditions
      affording the cross-coupled products. In addition, the reaction of 3
      haloselenophenes with boronic acids gave the corresponding Suzuki-type products
      in good yields. 

PMID- 24038326
TI  - The rapidly expanding world of rapidly progressive encephalopathy.

PMID- 24038327
TI  - Nonlinear responses for chromosome and gene level effects induced by vinyl
      acetate monomer and its metabolite, acetaldehyde in TK6 cells.
AB  - Vinyl acetate monomer (VAM) produced rat nasal tumors at concentrations in the
      hundreds of parts per million. However, VAM is weakly genotoxic in vitro and
      shows no genotoxicity in vivo. A European Union Risk Assessment concluded that
      VAM's hydrolysis to acetaldehyde (AA), via carboxylesterase, is a critical key
      event in VAM's carcinogenic potential. In the following study, we observed
      increases in micronuclei (MN) and thymidine kinase (Tk) mutants that were
      dependent on the ability of TK6 cell culture conditions to rapidly hydrolyze VAM
      to AA. Heat-inactivated horse serum demonstrated a high capacity to hydrolyze VAM
      to AA; this activity was highly correlated with a concomitant increase in MN. In
      contrast, heat-inactivated fetal bovine serum (FBS) did not hydrolyze VAM and no
      increase in MN was observed. AA's ability to induce MN was not impacted by either
      serum since it directly forms Schiff bases with DNA and proteins. Increased
      mutant frequency at the Tk locus was similarly mitigated when AA formation was
      not sufficiently rapid, such as incubating VAM in the presence of FBS for 4 hr.
      Interestingly, neither VAM nor AA induced mutations at the HPRT locus. Finally,
      cytotoxicity paralleled genotoxicity demonstrating that a small degree of
      cytotoxicity occurred prior to increases in MN. These results established 0.25 mM
      as a consistent concentration where genotoxicity first occurred for both VAM and
      AA provided VAM is hydrolyzed to AA. This information further informs significant
      key events related to the mode of action of VAM-induced nasal mucosal tumors in
      rats.

PMID- 24038328
TI  - MHC class II transactivator is an in vivo regulator of osteoclast differentiation
      and bone homeostasis co-opted from adaptive immunity.
AB  - The molecular networks controlling bone homeostasis are not fully understood. The
      common evolution of bone and adaptive immunity encourages the investigation of
      shared regulatory circuits. MHC Class II Transactivator (CIITA) is a master
      transcriptional co-activator believed to be exclusively dedicated for antigen
      presentation. CIITA is expressed in osteoclast precursors, and its expression is
      accentuated in osteoporotic mice. We thus asked whether CIITA plays a role in
      bone biology. To this aim, we fully characterized the bone phenotype of two mouse
      models of CIITA overexpression, respectively systemic and restricted to the
      monocyte-osteoclast lineage. Both CIITA-overexpressing mouse models revealed
      severe spontaneous osteoporosis, as assessed by micro-computed tomography and
      histomorphometry, associated with increased osteoclast numbers and enhanced in
      vivo bone resorption, whereas osteoblast numbers and in vivo bone-forming
      activity were unaffected. To understand the underlying cellular and molecular
      bases, we investigated ex vivo the differentiation of mutant bone marrow
      monocytes into osteoclasts and immune effectors, as well as osteoclastogenic
      signaling pathways. CIITA-overexpressing monocytes differentiated normally into
      effector macrophages or dendritic cells but showed enhanced osteoclastogenesis,
      whereas CIITA ablation suppressed osteoclast differentiation. Increased c-fms and
      receptor activator of NF-kappaB (RANK) signaling underlay enhanced osteoclast
      differentiation from CIITA-overexpressing precursors. Moreover, by extending
      selected phenotypic and cellular analyses to additional genetic mouse models,
      namely MHC Class II deficient mice and a transgenic mouse line lacking a specific
      CIITA promoter and re-expressing CIITA in the thymus, we excluded MHC Class II
      expression and T cells from contributing to the observed skeletal phenotype.
      Altogether, our study provides compelling genetic evidence that CIITA, the
      molecular switch of antigen presentation, plays a novel, unexpected function in
      skeletal homeostasis, independent of MHC Class II expression and T cells, by
      exerting a selective and intrinsic control of osteoclast differentiation and bone
      resorption in vivo.

PMID- 24038329
TI  - Rational design, green synthesis, and initial evaluation of a series of full
      color tunable fluorescent dyes enabled by the copper-catalyzed N-arylation of 6
      phenyl pyridazinones and their application in cell imaging.
AB  - There is widespread interest in the application, optimization, and evolution of
      the transition-metal-catalyzed arylation of N-heteroarenes to discover full-color
      tunable fluorescent core frameworks. Inspired by the versatile roles of
      pyridazinone in organic synthesis and medicinal chemistry, herein, we report a
      simple and efficient copper-catalyzed cross-coupling reaction for the N
      functionalization of pyridazinones in neat water. To achieve the efficient
      conversion of pyridazinones and organic halides in aqueous phase, a series of
      copper-salen complexes composed of different Schiff base ligands were
      investigated by rational design. A final choice of fine-tuned hydrophilicity
      balanced with lipophilicity among the candidates was confirmed, which affords
      excellent activity towards the reaction of a wide range of pyridazinones and
      organic halides. More importantly, the products as N-substituted pyridazinones
      were synthesized rationally by this methodology as full-color tunable fluorescent
      agents (426-612 nm). The N2 position of pyridazinones was modified by different
      aryl group such as benzothiazole, N,N-dimethylaniline, 3-quinoline, 4
      isoquinoline and 2-thiophene, resulting in a series of full-color tunable
      fluorescent reagents. Meanwhile, the effects of electron-donating and electron
      withdrawing groups of the 6-substituted phenyl ring have also been investigated
      to optimize the fluorescent properties. These fluorescent core frameworks were
      studied in several cell lines as fluorescent dyes. Different colors from blue to
      red were observed by using fluorescence microscopy and confocal microscopy. 

PMID- 24038330
TI  - Signaling context modulates social function of silent bared-teeth displays in
      rhesus macaques (Macaca mulatta).
AB  - The signaling context has been found to change the meaning of the silent bared
      teeth display (SBT) in pigtail macaques (Macaca nemestrina) such that the SBT in
      apparently peaceful contexts communicates subordination, a long-term pattern of
      behavior, whereas in conflict contexts it communicates immediate submission
      (PNAS, 104: 1581-1586). However, the context dependent nature of the SBT has not
      yet been explored in other species. We investigated SBT usage with respect to
      grooming, severe aggression, and signaler-receiver sex, rank difference, and body
      size in seven captive groups of rhesus macaques. Peaceful SBTs were given most
      often to male receivers by male and female signalers whereas conflict SBTs were
      given to both male and female receivers primarily by female signalers. Male
      signalers rarely gave SBTs (peaceful or conflict) to female receivers. Unlike
      pigtail macaques, peaceful SBTs in rhesus were often accompanied by withdrawal
      behavior (referred to as peaceful SBT-leave), which influenced grooming, but not
      aggression, at the dyadic level. Severe aggression was less frequent among dyads
      using peaceful SBTs (regardless of withdrawal behavior) than those using conflict
      SBTs. In contrast, grooming was more frequent among dyads using peaceful SBT-stay
      signals than those using peaceful SBT-leave signals or conflict SBTs. In total,
      our results indicate that peaceful SBTs are a functionally different signal from
      conflict SBTs in rhesus macaques.

PMID- 24038331
TI  - Coil combination of multichannel MRSI data at 7 T: MUSICAL.
AB  - The goal of this study was to evaluate a new method of combining multi-channel
      (1)H MRSI data by direct use of a matching imaging scan as a reference, rather
      than computing sensitivity maps. Seven healthy volunteers were measured on a 7-T
      MR scanner using a head coil with a 32-channel array coil for receive-only and a
      volume coil for receive/transmit. The accuracy of prediction of the phase of the
      (1)H MRSI data with a fast imaging pre-scan was investigated with the volume
      coil. The array coil (1)H MRSI data were combined using matching imaging data as
      coil combination weights. The signal-to-noise ratio (SNR), spectral quality,
      metabolic map quality and Cramer-Rao lower bounds were then compared with the
      data obtained by two standard methods, i.e. using sensitivity maps and the first
      free induction decay (FID) data point. Additional noise decorrelation was
      performed to further optimize the SNR gain. The new combination method improved
      significantly the SNR (+29%), overall spectral quality and visual appearance of
      metabolic maps, and lowered the Cramer-Rao lower bounds (-34%), compared with the
      combination method based on the first FID data point. The results were similar to
      those obtained by the combination method using sensitivity maps, but the new
      method increased the SNR slightly (+1.7%), decreased the algorithm complexity,
      required no reference coil and pre-phased all spectra correctly prior to spectral
      processing. Noise decorrelation further increased the SNR by 13%. The proposed
      method is a fast, robust and simple way to improve the coil combination in (1)H
      MRSI of the human brain at 7 T, and could be extended to other (1)H MRSI
      techniques.

PMID- 24038332
TI  - Funnel plots for population-based cancer survival: principles, methods and
      applications.
AB  - Funnel plots are graphical tools designed to detect excessive variation in
      performance indicators by simple visual inspection of the data. Their main use in
      the biomedical domain so far has been to detect publication bias in meta
      analyses, but they have also been recommended as the most appropriate way to
      display performance indicators for a vast range of health-related outcomes. Here,
      we extend the use of funnel plots to population-based cancer survival and several
      related measures. We present three applications to familiarise the reader with
      their interpretation. We propose funnel plots for various cancer survival
      measures, as well as age-standardised survival, trends in survival and excess
      hazard ratios. We describe the components of a funnel plot and the formulae for
      the construction of the control limits for each of these survival measures. We
      include three transformations to construct the control limits for the survival
      function: complementary log-log, logit and logarithmic transformations. We
      present applications of funnel plots to explore the following: (i) small-area and
      temporal variation in cancer survival; (ii) racial and geographical variation in
      cancer survival; and (iii) geographical variation in the excess hazard of death.
      Funnel plots provide a simple and informative graphical tool to display
      geographical variation and trend in a range of cancer survival measures. We
      recommend their use as a routine instrument for cancer survival comparisons, to
      inform health policy makers in planning and assessing cancer policies. We
      advocate the use of the complementary log-log or logit transformation to
      construct the control limits for the survival function.

PMID- 24038333
TI  - Improving study design for antidepressant effectiveness assessment.
AB  - Antidepressants effectiveness in major depressive disorder (MDD) is still
      questioned because the extrapolation of randomized controlled trial (RCT) results
      to "real life" settings is problematic. The application of the RCT paradigm in a
      disorder of this type, where global care plays a central role, raises questions
      regarding the internal and external validity of this type of study. Outcome
      measurement, attrition rates, the ability of the double-blind design to control
      for expectations, placebo response, the representativeness of trial participants
      and publication bias are major methodological pitfalls. This review discusses
      these issues. It is illustrated using original data and proposes some
      alternatives for assessing antidepressant effectiveness via different approaches.
      Some are easy to implement, such as ecological measures, qualitative approaches,
      improvement of analytical strategy and improvement of blinding procedures. Some
      are sophisticated, involving temporary deception to deal with the confounding
      effect of expectations, and they raise ethical issues. Others resort to external
      validity, this being the case in observational studies. But all are necessary to
      explore antidepressant effectiveness.

PMID- 24038334
TI  - Precolumn o-phthalaldehyde-N-acetyl-L-cysteine derivatization followed by RP-HPLC
      separation and fluorescence detection of sitagliptin enantiomers in rat plasma.
AB  - An indirect reversed-phase high-performance liquid chromatographic separation and
      fluorescence detection of sitagliptin enantiomers in rat plasma was developed and
      validated. Deproteinized rat plasma containing racemic sitagliptin was
      derivatized with o-phthalaldehyde and N-acetyl-L-cysteine under alkaline
      conditions, converted to diastereomers, and separated on a Lichrospher 100 RP-18e
      column using 20 mM phosphate buffer and methanol (45:55 v/v) as a mobile phase
      under isocratic mode of elution at a flow rate of 1.0 mL/min. Fluorescence
      detection was performed at 330 and 450 nm as excitation and emission wavelengths,
      respectively. The method was linear in the range of 50-5000 ng/ mL for both
      enantiomers. The intra- and interday accuracy and precision were within the
      predefined limits of <=15% at all concentrations. The method was successfully
      applied to a pharmacokinetic study of sitagliptin after 5 mg/kg oral
      administration to Wistar rats. Robustness of the method was evaluated using
      design of experiments.

PMID- 24038335
TI  - New cyclodextrin-bearing 8-hydroxyquinoline ligands as multifunctional molecules.
AB  - Recent investigations have rekindled interest in 8-hydroxyquinolines as
      therapeutic agents for cancer, Alzheimer's disease, and other neurodegenerative
      disorders. Three new beta-cyclodextrin conjugates of 8-hydroxyquinolines and
      their copper(II) and zinc(II) complexes have been synthesized and characterized
      spectroscopically. In addition to improving aqueous solubility, due to the
      presence of the cyclodextrin moiety, the hybrid systems have interesting
      characteristics including antioxidant activity, and their copper(II) complexes
      are efficient superoxide dismutase (SOD) mimics. The ligands and their copper(II)
      complexes show low cytotoxicity, attributed to the presence of the cyclodextrin
      moiety. These compounds have potential as therapeutic agents in diseases related
      both to metal dyshomeostasis and oxidative stress. 

PMID- 24038336
TI  - 25th anniversary article: Engineering hydrogels for biofabrication.
AB  - With advances in tissue engineering, the possibility of regenerating injured
      tissue or failing organs has become a realistic prospect for the first time in
      medical history. Tissue engineering - the combination of bioactive materials with
      cells to generate engineered constructs that functionally replace lost and/or
      damaged tissue - is a major strategy to achieve this goal. One facet of tissue
      engineering is biofabrication, where three-dimensional tissue-like structures
      composed of biomaterials and cells in a single manufacturing procedure are
      generated. Cell-laden hydrogels are commonly used in biofabrication and are
      termed "bioinks". Hydrogels are particularly attractive for biofabrication as
      they recapitulate several features of the natural extracellular matrix and allow
      cell encapsulation in a highly hydrated mechanically supportive three-dimensional
      environment. Additionally, they allow for efficient and homogeneous cell seeding,
      can provide biologically-relevant chemical and physical signals, and can be
      formed in various shapes and biomechanical characteristics. However, despite the
      progress made in modifying hydrogels for enhanced bioactivation, cell survival
      and tissue formation, little attention has so far been paid to optimize hydrogels
      for the physico-chemical demands of the biofabrication process. The resulting
      lack of hydrogel bioinks have been identified as one major hurdle for a more
      rapid progress of the field. In this review we summarize and focus on the
      deposition process, the parameters and demands of hydrogels in biofabrication,
      with special attention to robotic dispensing as an approach that generates
      constructs of clinically relevant dimensions. We aim to highlight this current
      lack of effectual hydrogels within biofabrication and initiate new ideas and
      developments in the design and tailoring of hydrogels. The successful development
      of a "printable" hydrogel that supports cell adhesion, migration, and
      differentiation will significantly advance this exciting and promising approach
      for tissue engineering. 

PMID- 24038337
TI  - Using cost-effectiveness estimates from survey data to guide commissioning: an
      application to home care.
AB  - The aim is to describe and trial a pragmatic method to produce estimates of the
      incremental cost-effectiveness of care services from survey data. The main
      challenge is in estimating the counterfactual; that is, what the patient's
      quality of life would be if they did not receive that level of service. A
      production function method is presented, which seeks to distinguish the variation
      in care-related quality of life in the data that is due to service use as opposed
      to other factors. A problem is that relevant need factors also affect the amount
      of service used and therefore any missing factors could create endogeneity bias.
      Instrumental variable estimation can mitigate this problem. This method was
      applied to a survey of older people using home care as a proof of concept. In the
      analysis, we were able to estimate a quality-of-life production function using
      survey data with the expected form and robust estimation diagnostics. The
      practical advantages with this method are clear, but there are limitations. It is
      computationally complex, and there is a risk of misspecification and biased
      results, particularly with IV estimation. One strategy would be to use this
      method to produce preliminary estimates, with a full trial conducted thereafter,
      if indicated.

PMID- 24038338
TI  - Synthetic and DFT studies towards a unified approach to phlegmarine alkaloids:
      aza-Michael intramolecular processes leading to 5-oxodecahydroquinolines.
AB  - A diastereoselective synthesis of cis-5-oxodecahydroquinolines is described in
      which three stereocenters are generated in a one-pot reaction. The reaction
      involves a lithium hydroxide-promoted Robinson annulation/intramolecular aza
      Michael domino process from an achiral acyclic tosylamine-tethered beta-keto
      ester. The development and scope of this reaction was facilitated through the use
      of DFT-based mechanistic studies, which enabled the observed diastereodivergent
      course of the azacyclization to be rationalized. The varying stereochemistry and
      stability of the resulting decahydroquinolines was found to depend on whether a
      beta-keto ester or ketone were embedded in the substrates undergoing
      aminocyclization. This synthetic approach gave access not only to both
      diastereomeric cis-decahydroquinolines from the same precursor, but also to the
      corresponding trans isomers, through an epimerization processes of the
      corresponding N-unsubstituted cis-5-oxodecahydroquinolines. The described
      methodology provides advanced building-blocks with the three relative
      stereochemistries required for the total synthesis of phlegmarine alkaloids. 

PMID- 24038341
TI  - Therapeutic prospects for Parkinson disease.
AB  - Dopaminergic therapies such as levodopa have provided benefit for millions of
      patients with Parkinson's disease (PD) and revolutionized the treatment of this
      disorder. However patients continue to experience disability despite the best of
      modern treatment. Dopaminergic and surgical therapies are associated with
      potentially serious side effects. Non-motor and non-dopaminergic features such as
      freezing, falling, and dementia are not adequately controlled with available
      medications and represent the major source of disability for advanced patients.
      And, the disease continues to relentlessly progress. Major therapeutic unmet
      needs include a dopaminergic therapy that is not associated with serious side
      effects, a therapy that addresses the non-motor and non-dopaminergic features of
      the disease, and a disease-modifying therapy that slows or stops disease
      progression. This review will consider current attempts to address these issues
      and the obstacles that must be overcome in order to develop more effective
      therapies for PD.

PMID- 24038340
TI  - Catabolism of host-derived compounds during extracellular bacterial infections.
AB  - Efficient catabolism of host-derived compounds is essential for bacterial
      survival and virulence. While these links in intracellular bacteria are well
      studied, such studies in extracellular bacteria lag behind, mostly for technical
      reasons. The field has identified important metabolic pathways, but the
      mechanisms by which they impact infection and in particular, establishing the
      importance of a compound's catabolism versus alternate metabolic roles has been
      difficult. In this review we will examine evidence for catabolism during
      extracellular bacterial infections in animals and known or potential roles in
      virulence. In the process, we point out key gaps in the field that will require
      new or newly adapted techniques.

PMID- 24038342
TI  - Copper-catalyzed oxidative benzylarylation of acrylamides by benzylic C-H bond
      functionalization for the synthesis of oxindoles.
AB  - Radically changing benzyls: An efficient method for the benzylarylation of
      activated alkenes has been developed through a copper-catalyzed tandem radical
      addition/cyclization strategy (see scheme). This oxidative coupling between
      acrylamides and benzylic hydrocarbons provides access to diverse alkyl
      substituted oxindoles in good to excellent yields. A variety of functional groups
      were tolerated in this transformation (TBPB = tert-butylperoxy benzoate).

PMID- 24038343
TI  - The effect of angiotensin inhibition on urinary incontinence: data from the
      National Health and Nutrition Examination Survey (2001-2008).
AB  - INTRODUCTION: Local renin-angiotensin systems exist within the genitourinary
      tract, specifically in the bladder and urethra. Experimental data suggest that
      angiotensin receptor blockade with either angiotensin converting enzyme (ACE)
      inhibitors or angiotensin receptor blockers (ARBs) decreases both detrusor
      overactivity and urethral sphincter tone leading to decreased urge incontinence
      (UUI) and increased stress urinary incontinence (SUI). This has not been examined
      in a human population. METHODS: Data from the National Health and Nutrition
      Examination Survey (NHANES) was accessed for the years 2001-2008. Multivariate
      logistic regression was used for modeling. RESULTS: We studied 8,754 females and
      8,886 males who met inclusion criteria. Use of ACE inhibitors or ARBs was not
      associated with a change in SUI in either men or women. In men, use of an ACE
      inhibitor or ARB was associated with a statistically significant 25-30% decrease
      in UUI (monthly or any urge incontinence). A similar, albeit non-significant
      trend was also seen for daily and weekly UUI. Other antihypertensive medications
      (diuretics, beta-blockers, calcium-channel blockers) were not associated with a
      decrease in UUI. In subanalysis, duration of ACE inhibitor or ARB use did not
      alter the strength of the effect on UUI nor did an elevated prostate specific
      antigen (PSA) level (used as a surrogate for bladder outlet obstruction due to
      benign prostatic hypertrophy). ACE inhibitor and ARB use did not affect UUI rates
      in women, though did show a trend for improvement in nulliparous women without
      SUI. CONCLUSION: Angiotensin receptor blockade may be a viable treatment approach
      for the treatment of UUI, especially in men.

PMID- 24038345
TI  - Diffusing capacity and forced vital capacity in 5,003 asbestos-exposed workers:
      relationships to interstitial fibrosis (ILO profusion score) and pleural
      thickening.
AB  - BACKGROUND: Asbestosis is an interstitial lung disease whose radiographic
      severity has long been graded by the International Labour Office (ILO) profusion
      score. Its effect on pulmonary function is further impacted by asbestos related
      pleural thickening. OBJECTIVES: This report aims to describe the relationships
      between radiographic grading of interstitial and pleural fibrosis and a key test
      of pulmonary function, the diffusing capacity, which measures gas exchange and
      has rarely been assessed in large groups, and to confirm the relationship to an
      independent test of pulmonary function, the vital capacity, which measures a
      mechanical property of the lungs. METHODS: The data were derived from a survey
      during the period 1997-2004 of 5,003 workers (all white males) exposed to
      asbestos in various trades. Tests included chest radiographs read by a certified
      expert ("B") reader, forced vital capacity (FVC), and carbon monoxide diffusing
      capacity (DLco). Cigarette smoking was adjusted for in the predictive equation
      for DLCO . Workers were evaluated at a mobile facility at work sites in four
      southern states. RESULTS: Both diffusing capacity and vital capacity were
      negatively correlated with profusion score over the full spectrum of radiographic
      severity. ILO profusion scores 0/1 (conventionally classified as normal) and 1/0
      (conventionally classified as abnormal) were associated with similar diffusing
      capacity and vital capacity values. The highest profusion scores were associated
      with a greater proportionate decrease in diffusing capacity than in FVC. Both
      tests showed an effect of pleural fibrosis. CONCLUSIONS: Both radiographic
      severity graded by the profusion score and pleural thickening are correlated with
      two independent measures of pulmonary function. FVC (which had been reported in
      smaller work forces) and DLCO (which has not been reported). Both measures show a
      decrease from normal to intermediate (0/1, 1/0) scores and a further decrease
      with greater scores, demonstrating the consistency of radiographic and functional
      assessments.

PMID- 24038346
TI  - Extracellular amyloid beta 42 causes necrosis, inhibition of nuclear division,
      and mitotic disruption under both folate deficient and folate replete conditions
      as measured by the cytokinesis-block micronucleus cytome assay.
AB  - Alzheimer's disease is associated with accumulation of extracellular beta amyloid
      peptide 42 (Abeta42) which may induce DNA damage and reduce cellular regenerative
      potential. These effects may be exacerbated under conditions of folate
      deficiency. The aim of this study was to investigate whether extracellular
      Abeta42 induces DNA damage and cell death in human peripheral lymphocytes and
      whether there is an interactive effect between extracellular Abeta42 and folic
      acid status. Peripheral blood lymphocytes were cultured in medium under
      conditions of both low and high folate (20 and 200 nM, respectively) and
      challenged with either Abeta42 or the physiologically normal form Abeta40 (both
      at 5, 10, 15 uM). Genome stability and cytotoxicity events were investigated
      using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay. Outcome
      measures scored included the nuclear division index (NDI), necrosis, apoptosis,
      binucleated cells with micronuclei (MN), nucleoplasmic bridges (NPB), and nuclear
      buds (NBUD) and abnormally shaped nuclei (circular, (CIR) and horse-shoe, (HS)
      that may be indicative of mitotic disruption. Folic acid deficiency significantly
      reduced NDI (P < 0.001) and increased all the DNA damage biomarkers (MN, NPB,
      NBUD, HS, CIR), (P < 0.001). In contrast, exposure to Abeta40 had no impact on
      CBMN cytome biomarkers but Abeta42 significantly reduced NDI (P < 0.01),
      increased necrosis (P < 0.05) and frequency of cells with circular nuclei (P <
      0.01). There was no evidence of an interaction between Abeta42 and folic acid
      with respect to CBMN cytome biomarkers. Extracellular Abeta42 appears to have
      cytotoxic and cytostatic effects but its effect on chromosomal instability
      appears to be small relative to folate deficiency.

PMID- 24038347
TI  - Gold-catalyzed oxidative cycloadditions to activate a quinoline framework.
AB  - Going for gold! Gold-catalyzed reactions of 3,5- and 3,6-dienynes with 8
      alkylquinoline oxides results in an oxidative cycloaddition with high
      stereospecificity (see scheme; EWG = electron-withdrawing group); this process
      involves a catalytic activation of a quinoline framework. The reaction mechanism
      involves the intermediacy of alpha-carbonyl pyridinium ylides (I) in a concerted
      [3+2]-cycloaddition with a tethered alkene. 

PMID- 24038348
TI  - Measuring agreement in method comparison studies with heteroscedastic
      measurements.
AB  - We propose a methodology for evaluation of agreement between two methods of
      measuring a continuous variable whose variability changes with magnitude. This
      problem routinely arises in method comparison studies that are common in health
      related disciplines. Assuming replicated measurements, we first model the data
      using a heteroscedastic mixed-effects model, wherein a suitably defined true
      measurement serves as the variance covariate. Fitting this model poses some
      computational difficulties as the likelihood function is not available in a
      closed form. We deal with this issue by suggesting four estimation methods to
      obtain approximate maximum likelihood estimates. Two of these methods are based
      on numerical approximation of the likelihood, and the other two are based on
      approximation of the model. Next, we extend the existing agreement evaluation
      methodology designed for homoscedastic data to work under the proposed
      heteroscedastic model. This methodology can be used with any scalar measure of
      agreement. Simulations show that the suggested inference procedures generally
      work well for moderately large samples. They are illustrated by analyzing a data
      set of cholesterol measurements.

PMID- 24038349
TI  - The fallacy of thresholds used in defining response and remission in depression
      rating scales.
AB  - Response and remission are determined by the proportion of people who fall below
      a threshold score on depression rating scales. This calculation implies a
      possibility of false positives (FP) and false negatives (FN) depending on
      sensitivity and specificity of the threshold used, but also on response and
      remission rates. A simulation illustrates the methodological consequences of this
      phenomenon in a comparative trial where response and remission rates differ
      between groups: the probability of being misclassified differs between groups,
      and measures of association (relative risk and odds ratio) are biased.
      Alternatives are proposed to cope with this misclassification bias.

PMID- 24038350
TI  - Enantioseparation and determination of the chiral fungicide furametpyr
      enantiomers in rice, soil, and water by high-performance liquid chromatography.
AB  - The chiral fungicide furametpyr is widely used in the rice field to control rice
      sheath blight; however, furametpyr enantiomers are treated as just one compound
      in traditional achiral analysis, which gives only partial information. An
      effective chiral analytical method was developed for the resolution and
      determination of the fungicide furametpyr enantiomers in rice, soil, and water
      samples. Furametpyr enantiomers were excellently separated and determined on a
      Chiralpak AD-H column with n-hexane/ethanol (90:10, v/v) as mobile phase at a
      flow rate of 0.8 mL min(-1) with UV detection at 220 nm. The resolution was up to
      8.85. The first eluted enantiomer was (+)-furametpyr and the second eluted one
      was (-)-furametpyr. The effects of mobile-phase composition and column
      temperature on the enantioseparation were evaluated. The method was validated for
      linearity, repeatability, accuracy, limit of detection (LOD), and limit of
      quantification LOQ. LOD was 2.0 ug kg(-1) in water, 0.02 mg kg(-1) in soil, and
      0.07 mg kg(-1) in rice with an LOQ of 6.7 ug kg(-1) in water, 0.07 mg kg(-1) in
      soil, and 0.23 mg kg(-1) in rice. The average recoveries of the pesticide in all
      matrices ranged from 73.1 to 101.8% for all fortification levels. The precision
      values associated with the analytical method, expressed as relative standard
      deviation (RSD) values, were below 14.0% in all matrices. The methodology was
      successfully applied for the enantioselective analysis of furametpyr enantiomers
      in real samples.

PMID- 24038351
TI  - Programmable mechanical resonances in MEMS by localized joule heating of phase
      change materials.
AB  - A programmable micromechanical resonator based on a VO2 thin film is reported.
      Multiple mechanical eigenfrequency states are programmed using Joule heating as
      local power source, gradually driving the phase transition of VO2 around its
      Metal-Insulator transition temperature. Phase coexistence of domains is used to
      tune the stiffness of the device via local control of internal stresses and
      mechanical properties. This study opens perspectives for developing mechanically
      configurable nanostructure arrays. 

PMID- 24038352
TI  - Predicting enhancer transcription and activity from chromatin modifications.
AB  - Enhancers play a pivotal role in regulating the transcription of distal genes.
      Although certain chromatin features, such as the histone acetyltransferase P300
      and the histone modification H3K4me1, indicate the presence of enhancers, only a
      fraction of enhancers are functionally active. Individual chromatin marks, such
      as H3K27ac and H3K27me3, have been identified to distinguish active from inactive
      enhancers. However, the systematic identification of the most informative single
      modification, or combination thereof, is still lacking. Furthermore, the
      discovery of enhancer RNAs (eRNAs) provides an alternative approach to directly
      predicting enhancer activity. However, it remains challenging to link chromatin
      modifications to eRNA transcription. Herein, we develop a logistic regression
      model to unravel the relationship between chromatin modifications and eRNA
      synthesis. We perform a systematic assessment of 24 chromatin modifications in
      fetal lung fibroblast and demonstrate that a combination of four modifications is
      sufficient to accurately predict eRNA transcription. Furthermore, we compare the
      ability of eRNAs and H3K27ac to discriminate enhancer activity. We demonstrate
      that eRNA is more indicative of enhancer activity. Finally, we apply our
      fibroblast trained model to six other cell-types and successfully predict eRNA
      synthesis. Thus, we demonstrate the learned relationships are general and
      independent of cell-type. We provided a powerful tool to identify active
      enhancers and reveal the relationship between chromatin modifications, eRNA
      production and enhancer activity. 

PMID- 24038353
TI  - Expression-level optimization of a multi-enzyme pathway in the absence of a high
      throughput assay.
AB  - Engineered metabolic pathways often suffer from flux imbalances that can
      overburden the cell and accumulate intermediate metabolites, resulting in reduced
      product titers. One way to alleviate such imbalances is to adjust the expression
      levels of the constituent enzymes using a combinatorial expression library.
      Typically, this approach requires high-throughput assays, which are unfortunately
      unavailable for the vast majority of desirable target compounds. To address this,
      we applied regression modeling to enable expression optimization using only a
      small number of measurements. We characterized a set of constitutive promoters in
      Saccharomyces cerevisiae that spanned a wide range of expression and maintained
      their relative strengths irrespective of the coding sequence. We used a
      standardized assembly strategy to construct a combinatorial library and express
      for the first time in yeast the five-enzyme violacein biosynthetic pathway. We
      trained a regression model on a random sample comprising 3% of the total library,
      and then used that model to predict genotypes that would preferentially produce
      each of the products in this highly branched pathway. This generalizable method
      should prove useful in engineering new pathways for the sustainable production of
      small molecules. 

PMID- 24038354
TI  - Manteia, a predictive data mining system for vertebrate genes and its
      applications to human genetic diseases.
AB  - The function of genes is often evolutionarily conserved, and comparing the
      annotation of ortholog genes in different model organisms has proved to be a
      powerful predictive tool to identify the function of human genes. Here, we
      describe Manteia, a resource available online at http://manteia.igbmc.fr. Manteia
      allows the comparison of embryological, expression, molecular and etiological
      data from human, mouse, chicken and zebrafish simultaneously to identify new
      functional and structural correlations and gene-disease associations. Manteia is
      particularly useful for the analysis of gene lists produced by high-throughput
      techniques such as microarrays or proteomics. Data can be easily analyzed
      statistically to characterize the function of groups of genes and to correlate
      the different aspects of their annotation. Sophisticated querying tools provide
      unlimited ways to merge the information contained in Manteia along with the
      possibility of introducing custom user-designed biological questions into the
      system. This allows for example to connect all the animal experimental results
      and annotations to the human genome, and take advantage of data not available for
      human to look for candidate genes responsible for genetic disorders. Here, we
      demonstrate the predictive and analytical power of the system to predict
      candidate genes responsible for human genetic diseases. 

PMID- 24038355
TI  - Mismatch repair protein MSH2 regulates translesion DNA synthesis following
      exposure of cells to UV radiation.
AB  - Translesion DNA synthesis (TLS) can use specialized DNA polymerases to insert
      and/or extend nucleotides across lesions, thereby limiting stalled replication
      fork collapse and the potential for cell death. Recent studies have shown that
      monoubiquitinated proliferating cell nuclear antigen (PCNA) plays an important
      role in recruitment of Y-family TLS polymerases to stalled replication forks
      after DNA damage treatment. To explore the possible roles of other factors that
      regulate the ultraviolet (UV)-induced assembly of specialized DNA polymerases at
      arrested replication forks, we performed immunoprecipitation experiments combined
      with mass spectrometry and established that DNA polymerase kappa (Polkappa) can
      partner with MSH2, an important mismatch repair protein associated with
      hereditary non-polyposis colorectal cancer. We found that depletion of MSH2
      impairs PCNA monoubiquitination and the formation of foci containing Polkappa and
      other TLS polymerases after UV irradiation of cells. Interestingly, expression of
      MSH2 in Rad18-deficient cells increased UV-induced Polkappa and REV1 focus
      formation without detectable changes in PCNA monoubiquitination, indicating that
      MSH2 can regulate post-UV focus formation by specialized DNA polymerases in both
      PCNA monoubiquitination-dependent and -independent fashions. Moreover, we
      observed that MSH2 can facilitate TLS across cyclobutane pyrimidine dimers
      photoproducts in living cells, presenting a novel role of MSH2 in post-UV
      cellular responses. 

PMID- 24038356
TI  - The splicing landscape is globally reprogrammed during male meiosis.
AB  - Meiosis requires conserved transcriptional changes, but it is not known whether
      there is a corresponding set of RNA splicing switches. Here, we used RNAseq of
      mouse testis to identify changes associated with the progression from mitotic
      spermatogonia to meiotic spermatocytes. We identified ~150 splicing switches,
      most of which affect conserved protein-coding exons. The expression of many key
      splicing regulators changed in the course of meiosis, including downregulation of
      polypyrimidine tract binding protein (PTBP1) and heterogeneous nuclear RNP A1,
      and upregulation of nPTB, Tra2beta, muscleblind, CELF proteins, Sam68 and T-STAR.
      The sequences near the regulated exons were significantly enriched in target
      sites for PTB, Tra2beta and STAR proteins. Reporter minigene experiments
      investigating representative exons in transfected cells showed that PTB binding
      sites were critical for splicing of a cassette exon in the Ralgps2 mRNA and a
      shift in alternative 5' splice site usage in the Bptf mRNA. We speculate that
      nPTB might functionally replace PTBP1 during meiosis for some target exons, with
      changes in the expression of other splicing factors helping to establish meiotic
      splicing patterns. Our data suggest that there are substantial changes in the
      determinants and patterns of alternative splicing in the mitotic-to-meiotic
      transition of the germ cell cycle. 

PMID- 24038358
TI  - Opening pathways of the DNA clamps proliferating cell nuclear antigen and Rad9
      Rad1-Hus1.
AB  - Proliferating cell nuclear antigen and the checkpoint clamp Rad9-Rad1-Hus1
      topologically encircle DNA and act as mobile platforms in the recruitment of
      proteins involved in DNA damage response and cell cycle regulation. To fulfill
      these vital cellular functions, both clamps need to be opened and loaded onto DNA
      by a clamp loader complex-a process, which involves disruption of the DNA clamp's
      subunit interfaces. Herein, we compare the relative stabilities of the interfaces
      using the molecular mechanics Poisson-Boltzmann solvent accessible surface
      method. We identify the Rad9-Rad1 interface as the weakest and, therefore, most
      likely to open during clamp loading. We also delineate the dominant interface
      disruption pathways under external forces in multiple-trajectory steered
      molecular dynamics runs. We show that, similar to the case of protein folding,
      clamp opening may not proceed through a single interface breakdown mechanism.
      Instead, we identify an ensemble of opening pathways, some more prevalent than
      others, characterized by specific groups of contacts that differentially
      stabilize the regions of the interface and determine the spatial and temporal
      patterns of breakdown. In Rad9-Rad1-Hus1, the Rad9-Rad1 and Rad9-Hus1 interfaces
      share the same dominant unzipping pathway, whereas the Hus1-Rad1 interface is
      disrupted concertedly with no preferred directionality. 

PMID- 24038360
TI  - Bankruptcy, medical insurance, and a law with unintended consequences.
AB  - Congress passed the Emergency Medical Treatment and Active Labor Act (EMTALA) in
      1986, guaranteeing a standard of medical care to anyone who entered an emergency
      room. This guarantee made default a more reliable substitute for medical
      insurance. I construct a tractable structural model of the medical insurance
      market and find that repealing EMTALA would increase the fraction of the
      population with insurance while decreasing its price.

PMID- 24038357
TI  - Histone posttranslational modifications and cell fate determination: lens
      induction requires the lysine acetyltransferases CBP and p300.
AB  - Lens induction is a classical embryologic model to study cell fate determination.
      It has been proposed earlier that specific changes in core histone modifications
      accompany the process of cell fate specification and determination. The lysine
      acetyltransferases CBP and p300 function as principal enzymes that modify core
      histones to facilitate specific gene expression. Herein, we performed conditional
      inactivation of both CBP and p300 in the ectodermal cells that give rise to the
      lens placode. Inactivation of both CBP and p300 resulted in the dramatic
      discontinuation of all aspects of lens specification and organogenesis, resulting
      in aphakia. The CBP/p300(-/-) ectodermal cells are viable and not prone to
      apoptosis. These cells showed reduced expression of Six3 and Sox2, while
      expression of Pax6 was not upregulated, indicating discontinuation of lens
      induction. Consequently, expression of alphaB- and alphaA-crystallins was not
      initiated. Mutant ectoderm exhibited markedly reduced levels of histone H3 K18
      and K27 acetylation, subtly increased H3 K27me3 and unaltered overall levels of
      H3 K9ac and H3 K4me3. Our data demonstrate that CBP and p300 are required to
      establish lens cell-type identity during lens induction, and suggest that
      posttranslational histone modifications are integral to normal cell fate
      determination in the mammalian lens. 

PMID- 24038359
TI  - E2F2 and CREB cooperatively regulate transcriptional activity of cell cycle
      genes.
AB  - E2F2 is essential for the maintenance of T lymphocyte quiescence. To identify the
      full set of E2F2 target genes, and to gain further understanding of the role of
      E2F2 in transcriptional regulation, we have performed ChIP-chip analyses across
      the genome of lymph node-derived T lymphocytes. Here we show that during
      quiescence, E2F2 binds the promoters of a large number of genes involved in DNA
      metabolism and cell cycle regulation, concomitant with their transcriptional
      silencing. A comparison of ChIP-chip data with expression profiling data on
      resting E2f2(-)(/)(-) T lymphocytes identified a subset of 51 E2F2-specific
      target genes, most of which are upregulated on E2F2 loss. Luciferase reporter
      assays showed a retinoblastoma-independent role for E2F2 in the negative
      regulation of these target genes. Importantly, we show that the DNA binding
      activity of the transcription factor CREB contributes to E2F2-mediated repression
      of Mcm5 and Chk1 promoters. siRNA-mediated CREB knockdown, expression of a
      dominant negative KCREB mutant or disruption of CREB binding by mutating a CRE
      motif on Mcm5 promoter, relieved E2F2-mediated transcriptional repression. Taken
      together, our data uncover a new regulatory mechanism for E2F-mediated
      transcriptional control, whereby E2F2 and CREB cooperate in the transcriptional
      repression of a subset of E2F2 target genes. 

PMID- 24038361
TI  - Lewis acid mediated vinyl-transfer reaction of alkynes to N-alkylimines by using
      the N-alkyl residue as a sacrificial hydrogen donor.
AB  - A variety of N-alkyl-alpha,alpha-dichloroaldimines were vinylated by terminal
      acetylenes in the presence of Lewis acids such as In(OTf)3 or BF3 ?OEt2 and
      hexafluoroisopropanol (HFIP) as an additive. The reaction proceeds at ambient
      temperature and leads to geometrically pure allylic beta,beta-dichloroamines.
      This approach is complementary to previously reported transition-metal-catalyzed
      vinyl-transfer methods, which are not applicable to aliphatic imines and are
      restricted to imines that contain an electron-withdrawing nitrogen substituent.
      In the present approach, terminal alkynes were used as a source of the vinyl
      residue, and the N-alkyl moiety of the imine acts as a sacrificial hydrogen
      donor. The additional advantage of this methodology is the fact that no external
      toxic or hazardous reducing agents or molecular hydrogen has to be used. This new
      methodology nicely combines a C(sp(2) )?C(sp) bond formation, hydride transfer,
      and an unusual cleavage of an unactivated C?N bond, thereby giving rise to
      functionalized primary allylic amines. A detailed experimental study supported by
      DFT calculations of the mechanism has been done. 

PMID- 24038362
TI  - Evaluating the scale-up for maternal and child survival: a common framework.
AB  - Programs to reduce mortality among women and children are the target of new
      resources and redoubled commitment as the 2015 date for achieving the Millennium
      Development Goals approaches. The need for a common evaluation framework to guide
      the collection, analysis and synthesis of evidence is increasingly evident. This
      paper presents such a framework in four parts: (1) a conceptual model for the
      scale-up to MDGs 4 and 5 for maternal and child survival; (2) recommended
      indicators for each part of the model that bring together the work of various
      existing technical groups and prioritize a limited number of indicators for
      standardization and common use; (3) guidelines for documenting program
      implementation and contextual factors that may affect program implementation and
      its effectiveness in reducing maternal and child mortality; and (4) design
      considerations in evaluating the scale-up. We first present an overview of what
      is known and/or agreed upon within each of these areas, and in the discussion
      highlight areas of uncertainty or where there are gaps to be addressed. 

PMID- 24038363
TI  - The challenges of managing severe dehydrating diarrhoea in a resource-limited
      setting.
AB  - Diarrhoea remains one of the most common causes of childhood deaths worldwide
      despite the widespread use of oral rehydration solution (ORS). The vast majority
      of the nearly 2 million diarrhoeal deaths occurring annually in children under
      five years of age are in south Asia and sub-Saharan Africa. Signs of critical
      illness in severely dehydrated children are poorly recognised, and although
      considerable efforts have gone into establishing the management of diarrhoeal
      disease in general, there is surprisingly little understanding of the aetiology,
      metabolic processes and risk factors for the very high mortality associated with
      severe dehydrating diarrhoea (SDD). We suggest that in many resource-poor
      settings, the degree of fluid requirement as well as the prevalence of
      electrolyte disturbances are seriously under-recognised and may be contributing
      significantly to mortality. The heterogeneity of children with SDD renders the
      generic 'one size fits all' approach to fluid and electrolyte management in these
      critically ill children inadequate. In this review we will highlight SDD as an
      important target for research in resource-limited settings, and emphasise the
      need to re-evaluate the efficacy of prevailing intravenous fluid protocols in
      well conducted multi-centre interventional trials. 

PMID- 24038364
TI  - Safety of sulfadoxine/pyrimethamine for intermittent preventive treatment of
      malaria in infants: evidence from large-scale operational research in southern
      Tanzania.
AB  - Intermittent preventive treatment with sulfadoxine/pyrimethamine (SP) is
      recommended for malaria prevention in infants (IPTi-SP). Serious adverse events,
      including Stevens-Johnson syndrome (SJS), have been reported following exposure
      to SP, but few infant-specific data exist. The safety of IPTi-SP was evaluated as
      part of a pilot implementation programme in southern Tanzania using three
      methods: spontaneous adverse event reporting to capture suspected adverse drug
      reactions (ADR); a census survey documenting rash-related hospital admissions
      among children < 2 years of age; and verbal autopsies (VA) completed for rash
      related deaths in 2-11-month-olds. Approximately 82 000 IPTi-SP doses were
      administered to approximately 29 000 children. In total, 119 suspected ADRs were
      reported, 13 in children aged <2 years, only one of whom had received IPTi-SP.
      The census involved 243 612 households. Only one rash-related admission was
      reported amongst 1292 children aged 2-11 months, but this child had no history of
      exposure to SP. Moreover, 30 of 699 deaths in 2-11-month-olds were said to have
      been associated with a skin rash. The rates of rash-associated death were
      0.59/1000 person-years at risk (PYAR) and 1.17/1000 PYAR in intervention and
      comparison areas, respectively (P = 0.79). VAs did not suggest SJS or any other
      ADR. We conclude that IPTi-SP is associated with a very low incidence of severe
      skin reactions. [ClinicalTrials.gov identifier: NCT00152204]. 

PMID- 24038365
TI  - Improved tuberculosis smear detection in resource-limited settings: Combined
      bleach concentration and LED fluorescence microscopy.
AB  - Improved diagnostics for tuberculosis is a high priority in resource-limited
      settings (RLS). Sputum concentration and fluorescence microscopy (FM) are
      standard techniques in developed countries where appropriate biosafety
      precautions are possible. Recently, inexpensive fluorescent lenses using LED
      light sources have made auramine-based FM more feasible in RLS. Sterilization of
      sputum with bleach protects lab personnel and, combined with concentration,
      increases the sensitivity of microscopic detection. We compared the effect of
      both bleach concentration and FM with LED based lenses to culture for the
      detection of tuberculosis in military medical hospitals in Addis Ababa, Ethiopia.
      Three sputum specimens were obtained from 409 patients (1227 total). Standard
      Ziehl-Neelsen (ZN) or auramine staining were compared with direct or bleach
      concentrated specimens. The prevalence by culture was 26%. Sensitivity of
      microscopic diagnosis was increased both by bleach concentration (14%) and
      auramine staining (5%). The overall yield of smear positivity varied from 21% for
      direct ZN to 27% for auramine after concentration (P<0.00001, Cochran test for
      matched proportions). Twenty-nine HIV+ patients were diagnosed with TB, but ten
      (34%), would have been missed with direct ZN staining. Bleach concentration and
      auramine staining with new LED fluorescent systems are cost-effective and safe
      methods to increase the diagnostic yield of smears, including in HIV-infected
      patients. 

PMID- 24038366
TI  - Planning schistosomiasis control: investigation of alternative sampling
      strategies for Schistosoma mansoni to target mass drug administration of
      praziquantel in East Africa.
AB  - In schistosomiasis control, there is a need to geographically target treatment to
      populations at high risk of morbidity. This paper evaluates alternative sampling
      strategies for surveys of Schistosoma mansoni to target mass drug administration
      in Kenya and Ethiopia. Two main designs are considered: lot quality assurance
      sampling (LQAS) of children from all schools; and a geostatistical design that
      samples a subset of schools and uses semi-variogram analysis and spatial
      interpolation to predict prevalence in the remaining unsurveyed schools.
      Computerized simulations are used to investigate the performance of sampling
      strategies in correctly classifying schools according to treatment needs and
      their cost-effectiveness in identifying high prevalence schools. LQAS performs
      better than geostatistical sampling in correctly classifying schools, but at a
      cost with a higher cost per high prevalence school correctly classified. It is
      suggested that the optimal surveying strategy for S. mansoni needs to take into
      account the goals of the control programme and the financial and drug resources
      available. 

PMID- 24038367
TI  - A qualitative study on stigma and coping strategies of patients with podoconiosis
      in Wolaita zone, Southern Ethiopia.
AB  - Podoconiosis (endemic non-filarial elephantiasis) is a neglected tropical disease
      that causes affected individuals intense social stigma. Although some studies
      have investigated community-based stigma against podoconiosis, none has yet
      attempted to assess coping strategies used by patients to counter stigma. This
      study aimed to describe and categorize the coping strategies employed by
      podoconiosis patients against stigma. From January-March 2010 data were gathered
      through in-depth interviews with 44 patients, six focus group discussions (with a
      total of 42 participants) and two key informant interviews. The coping strategies
      employed by patients to deal with stigma could be categorized into three areas:
      active, avoidant and through changing the relational meaning. Of these coping
      strategies, avoidant coping is the most negative since it encourages isolation
      and pushes those employing it towards more risky decisions. Many podoconiosis
      patients are forced to use this strategy through lack of control due to extreme
      poverty. Intervention programs must therefore create circumstances in which
      patients are empowered to actively cope with stigma and play a role in stigma
      reduction. 

PMID- 24038368
TI  - Monitoring lymphatic filariasis control in Tanzania: effect of repeated mass drug
      administration on circulating filarial antigen prevalence in young
      schoolchildren.
AB  - In most countries of Sub-Saharan Africa the control of lymphatic filariasis (LF)
      is based on annual mass drug administration (MDA) with a combination of
      ivermectin and albendazole, in order to interrupt transmission. We monitored the
      effect of four repeated MDAs with this combination, as implemented by the
      Tanzanian National Lymphatic Filariasis Elimination Programme (NLFEP), on the
      circulating filarial antigen (CFA) status of young schoolchildren. A new batch of
      Standard 1 pupils from 10 rural primary schools in Tanga Municipality were
      examined for CFA each year in September/October (691-848 children per survey;
      mean age of 7.5-8.1 years), from immediately before the first MDA until eight
      months after the fourth MDA. The overall pre-MDA prevalence of CFA was 25.2%.
      Only minor and non-significant change in prevalence was seen after the first two
      MDAs. However, this was followed by substantial and statistically significant
      decreases in subsequent surveys, and eight months after the fourth MDA the
      prevalence was only 6.4%. Continuous entomological surveillance in a village
      accommodating one of the schools showed progressive decrease in transmission
      right from the first MDA. The usefulness of screening young schoolchildren for
      CFA as a tool for monitoring the impact of MDA on LF transmission is discussed. 

PMID- 24038369
TI  - Glycaemic control in children with neonatal diabetes and type 1 diabetes in
      Vietnam.
AB  - Childhood diabetes care may be suboptimal in resource-poor countries. A cross
      sectional study of youths with diabetes aged <=19 years attending the three major
      paediatric centres in Vietnam was performed. Diabetes management was documented
      by questionnaire. Glycated haemoglobin (HbA1c) was measured with a fingerprick
      blood sample. Multiple linear regression analysis was used to examine factors
      associated with glycaemic control. In total, 105 patients participated,
      comprising 93 with type 1 diabetes and 12 with neonatal diabetes. The median age
      was 11.5 years [interquartile range (IQR) 6.4-14.5 years] and the median duration
      of diabetes was 2.6 years (IQR 1.5-6.1 years). Patients with type 1 diabetes
      performed few blood glucose tests per month (median 8, IQR 4-30). Mean HbA1c was
      higher in patients with type 1 diabetes compared with neonatal diabetes (9.9% vs.
      7.5%; P = 0.01). In type 1 diabetes using multivariate analysis, higher HbA1c was
      associated with older age (beta = 0.3, 95% CI 0.2-0.4; P < 0.001), lower
      frequency of blood glucose monitoring (beta = -0.06, 95% CI -0.10 to 0.12; P =
      0.01) and use of pre-mixed insulin (beta = -1.7, 95% CI -3.4 to 0.0; P = 0.05).
      In conclusion, international glycaemic control targets for childhood diabetes
      (HbA1c <7.5%) are not being achieved in Vietnam, and intensive diabetes
      management is rare. There is an urgent need to address barriers to achieving
      optimal control in this population. 

PMID- 24038370
TI  - HIV diagnoses in indigenous peoples: comparison of Australia, Canada and New
      Zealand.
AB  - In industrial countries, a number of factors put indigenous peoples at increased
      risk of HIV infection. National surveillance data between 1999 and 2008 provided
      diagnoses for Aboriginal and Torres Strait Islanders (Australia), First Nations,
      Inuit and Metis (Canada excluding Ontario and Quebec) and Maori (New Zealand).
      Each country provided similar data for a non-indigenous comparison population.
      Direct standardisation used the 2001 Canadian Aboriginal male population for
      comparison of five-year diagnosis rates in 1999-2003 and 2004-2008. Using the
      general population as denominators, we report diagnosis ratios for presumed
      heterosexual transmission, men who have sex with men (MSM) and intravenous drug
      users (IDU). Age standardised HIV diagnosis rates in indigenous peoples in Canada
      in 2004-2008 (178.1 and 178.4/100 000 for men and women respectively) were higher
      than in Australia (48.5 and 12.9/100 000) and New Zealand (41.9 and 4.3/100 000).
      Higher HIV diagnosis rates related to heterosexual contact among Aboriginal
      peoples, especially women, in Canada confirm a widening epidemic beyond the
      conventional risk groups. This potential of a generalised epidemic requires
      urgent attention in Aboriginal communities; available evidence can inform policy
      and action by all stakeholders. Although less striking in Australia and New
      Zealand, these findings may be relevant to indigenous peoples in other countries.

PMID- 24038371
TI  - Reported healthcare utilisation for childhood respiratory illnesses in Vellore,
      South India.
AB  - A 30-cluster survey using a modified WHO method was performed to assess the
      healthcare utilisation patterns for respiratory illnesses in Indian children < 5
      years of age. Families of 600 children were interviewed to assess respiratory
      illness and healthcare utilisation during the previous month as well as
      hypothetical healthcare-seeking behaviour in the future. Based on parental
      report, 381 children (63.5%) had experienced a respiratory illness 1 month prior
      to the interview; 10 children were reported to have had severe pneumonia, 49 non
      severe pneumonia and 322 upper respiratory illnesses (URI), extrapolating to 0.20
      (95% CI 0.1-0.4), 0.98 (0.7-1.3) and 6.44 (6.0-6.9) cases per child-year,
      respectively. Five severe pneumonia cases (50%) were reported to have directly
      accessed care at a secondary or tertiary care centre, whilst 18 children (36.7%)
      with non-severe pneumonia and 56 children (17.4%) with URI were reported to have
      been seen at secondary or tertiary centres. The remaining respiratory illnesses
      were reported to have been seen by primary care physicians, pharmacists,
      traditional healers and friends or were not seen by a healthcare professional.
      This community-based Indian study suggests that, in this community, tertiary care
      surveillance alone may not accurately sample community disease, even for severe
      illnesses. 

PMID- 24038372
TI  - Effect of sulphadoxine-pyrimethamine on neonatal birth weight and perceptions on
      its impact on malaria in pregnancy in an intermittent preventive treatment
      programme setting in Offinso District, Ghana.
AB  - This study evaluated the effect of sulphadoxine-pyrimethamine (SP) use in
      intermittent preventive treatment of malaria in pregnancy (IPTp) on birth weights
      of neonates in a stable malaria transmission area of Ghana, Offinso District.
      Routine delivery data from six health facilities over the period January 2005 to
      October 2007 were reviewed. In-depth interviews were conducted for health staff
      of these facilities to assess the effect of SP use in IPTp in pregnancy. SP-IPTp
      improved the birth weight of neonates and the effects of age, parity, term of
      pregnancy and sex of neonate also had significant influence on the birth weight
      (P < 0.0001). The variation in birth weight of the neonates, however, did not
      show significant difference (OR = 0.91, 95% CI 0.8-1.1, P >=0.26) over the period
      and seasonal variations had no effect on birth weight (OR = 0.84, 95% CI 0.7-1.1,
      P >=0.18). Health personnel attested to the fact that SP-IPTp had reduced the
      burden of malaria cases in pregnancy and improved birth weight of neonates. This
      study, thus, shows that successful implementation of the SP-IPTp strategy will
      improve the birth weight of neonates, and consequently reduce neonatal mortality.

PMID- 24038373
TI  - Cost of epilepsy in children attending a tertiary centre in Nigeria.
AB  - Epilepsy is one of the leading paediatric neurological disorders in Nigeria and
      many other parts of the world. There is very little documented on the economic
      costs of epilepsy in Nigeria and other countries in sub-Saharan Africa. This
      study was carried out to estimate the total cost of childhood epilepsy in a
      cohort of Nigerian children and therefore provide essential information on the
      economic burden of childhood epilepsy in Nigeria. A cost of illness study was
      performed on a cohort of 215 consecutive cases of epilepsy seen and treated at
      the University College Hospital, Ibadan, Nigeria. Data on demographics, clinical
      characteristics, utilization of resources and costs were collected. The total
      annual cost of epilepsy ranged from Nigerian naira (N)23 200 (US$155) to N3 298
      500 (US$21,900) with a median of N107 600 (US$717) per patient per year. Direct
      medical and non-medical costs accounted for 71.8% of the total mean annual cost
      of epilepsy. Anti-epileptic drug therapy and in-patient care accounted for 21.8%
      and 33.0% of the mean total annual cost respectively and more than half of the
      families expended over 20% of their total family income on the care of the child
      with epilepsy. The economic burden of childhood epilepsy in Nigeria is enormous
      with very high out-of-pocket expenses. 

PMID- 24038374
TI  - Evaluation of the lower limb vasculature before free fibula flap transfer. A
      prospective blinded comparison between magnetic resonance angiography and digital
      subtraction angiography.
AB  - Introduction The aim of this study was to compare magnetic resonance angiography
      (MRA) with digital subtraction angiography (DSA) in the preoperative assessment
      of crural arteries and their skin perforators prior to free fibular transfer.
      Patients and methods Fifteen consecutive patients, scheduled for free
      vascularized fibular flap transfer, were subjected to DSA as well as MRA of the
      crural arteries of both legs (n = 30). All DSA and MRA images were assessed
      randomly, blindly, and independently by two radiologists. Each of the assessors
      scored the degree of stenosis of various segments on a 5 point scale from 0
      (occlusive) to 4 (no stenosis). The Cohen's Kappa coefficient was used to assess
      the agreement between DSA and MRA scores. In addition, the number of cutaneous
      perforators were scored and the assessors were asked if they would advise against
      fibula harvest and transplantation based on the images. Results A Cohen's Kappa
      of 0.64, indicating "substantial agreement of stenosis severity scores" was found
      between the two imaging techniques. The sensitivity of MRA to detect a stenosis
      compared with DSA was 79% (CI 95%:60-91), and a specificity of 98% (CI 95%: 97
      99). In 53 out of 60 assessments, advice on suitability for transfer were equal
      between DSA and MRA. The median number of cutaneous perforators that perfuse the
      skin overlying the fibula per leg was one for DSA as well as MRA (P =
      0.142).Conclusions A substantial agreement in the assessment of stenosis severity
      was found between DSA and MRA. The results suggest that MRA is a good alternative
      to DSA in the preoperative planning of free fibula flap transplantation.

PMID- 24038375
TI  - Studies on photocatalytic CO(2) reduction over NH2 -Uio-66(Zr) and its
      derivatives: towards a better understanding of photocatalysis on metal-organic
      frameworks.
AB  - Metal-organic framework (MOF) NH2 -Uio-66(Zr) exhibits photocatalytic activity
      for CO2 reduction in the presence of triethanolamine as sacrificial agent under
      visible-light irradiation. Photoinduced electron transfer from the excited 2
      aminoterephthalate (ATA) to Zr oxo clusters in NH2 -Uio-66(Zr) was for the first
      time revealed by photoluminescence studies. Generation of Zr(III) and its
      involvement in photocatalytic CO2 reduction was confirmed by ESR analysis.
      Moreover, NH2 -Uio-66(Zr) with mixed ATA and 2,5-diaminoterephthalate (DTA)
      ligands was prepared and shown to exhibit higher performance for photocatalytic
      CO2 reduction due to its enhanced light adsorption and increased adsorption of
      CO2 . This study provides a better understanding of photocatalytic CO2 reduction
      over MOF-based photocatalysts and also demonstrates the great potential of using
      MOFs as highly stable, molecularly tunable, and recyclable photocatalysts in CO2
      reduction. 

PMID- 24038376
TI  - Cyclodextrin-modified zeolites: host-guest surface chemistry for the construction
      of multifunctional nanocontainers.
AB  - The functionalization of nanoporous zeolite L crystals with beta-cyclodextrin
      (CD) has been demonstrated. The zeolite surface was first modified with amino
      groups by using two different aminoalkoxysilanes. Then, 1,4-phenylene
      diisothiocyanate was reacted with the amino monolayer and used to bind CD
      heptamine by using its remaining isothiocyanate groups. The use of the different
      aminoalkoxysilanes, 3-aminopropyl dimethylethoxysilane (APDMES) and 3-aminopropyl
      triethoxysilane (APTES), led to drastic differences in uptake and release
      properties. Thionine was found to be absorbed and released from amino- and CD
      functionalized zeolites when APDMES was used, whereas functionalization by APTES
      led to complete blockage of the zeolite channels. Fluorescence microscopy showed
      that the CD groups covalently attached to the zeolite crystals could bind
      adamantyl-modified dyes in a specific and reversible manner. This strategy
      allowed the specific immobilization of His-tagged proteins by using combined host
      guest and His-tag-Ni-nitrilotriacetic acid (NTA) coordination chemistry. Such
      multifunctional systems have the potential for encapsulation of drug molecules
      inside the zeolite pores and non-covalent attachment of other (for example,
      targeting) ligand molecules on its surface. 

PMID- 24038377
TI  - Transforming growth factor-beta1 primes proliferating adult neural progenitor
      cells to electrophysiological functionality.
AB  - The differentiation of adult neural progenitors (NPCs) into functional neurons is
      still a limiting factor in the neural stem cell field but mandatory for the
      potential use of NPCs in therapeutic approaches. Neuronal function requires the
      appropriate electrophysiological properties. Here, we demonstrate that priming of
      NPCs using transforming growth factor (TGF)-beta1 under conditions that usually
      favor NPCs' proliferation induces electrophysiological neuronal properties in
      adult NPCs. Gene chip array analyses revealed upregulation of voltage-dependent
      ion channel subunits (Kcnd3, Scn1b, Cacng4, and Accn1), neurotransmitters, and
      synaptic proteins (Cadps, Snap25, Grik4, Gria3, Syngr3, and Gria4) as well as
      other neuronal proteins (doublecortin [DCX], Nrxn1, Sept8, and Als2cr3). Patch
      clamp analysis demonstrated that control-treated cells expressed only voltage
      dependent K(+) -channels of the delayed-rectifier type and the A-type channels.
      TGF-beta1-treated cells possessed more negative resting potentials than
      nontreated cells owing to the presence of delayed-rectifier and inward-rectifier
      channels. Furthermore, TGF-beta1-treated cells expressed voltage-dependent, TTX
      sensitive Na(+) channels, which showed increasing current density with TGF-beta1
      treatment duration and voltage-dependent (+)BayK8644-sensitive L-Type Ca(2+)
      channels. In contrast to nontreated cells, TGF-beta1-treated cells responded to
      current injections with action-potentials in the current-clamp mode. Furthermore,
      TGF-beta1-treated cells responded to application of GABA with an increase in
      membrane conductance and showed spontaneous synaptic currents that were blocked
      by the GABA-receptor antagonist picrotoxine. Only NPCs, which were treated with
      TGF-beta1, showed Na(+) channel currents, action potentials, and GABAergic
      currents. In summary, stimulation of NPCs by TGF-beta1 fosters a functional
      neuronal phenotype, which will be of relevance for future cell replacement
      strategies in neurodegenerative diseases or acute CNS lesions.

PMID- 24038378
TI  - Early onset dystonia and parkinsonism with abnormal globus pallidal signal in
      MRI: a diagnostic challenge.

PMID- 24038379
TI  - miR-495 enhances the sensitivity of non-small cell lung cancer cells to platinum
      by modulation of copper-transporting P-type adenosine triphosphatase A (ATP7A).
AB  - Copper-transporting P-type adenosine triphosphatase A (ATP7A) is associated with
      platinum drug resistance in non-small cell lung cancer (NSCLC). microRNAs
      (miRNAs) are a class of small non-coding RNA molecules that regulate gene
      expression at post-transcriptional level. In this study, the aim is to explore
      which miRNAs might participate in the platinum resistance by targeting ATP7A in
      NSCLC. Using real-time PCR-based miRNA expression profiling and bioinformatics,
      we selected miR-495 as a candidate miRNA. EGFP reporter assay, real-time PCR, and
      Western blot validated that ATP7A was a direct target for miR-495. The drug
      sensitivity assay indicated that miR-495 enhanced the cell response to cisplatin
      (CDDP) in NSCLC cells, while inhibition of miR-495 led to the opposite effects.
      Importantly, either overexpression or knockdown of ATP7A could override the
      effect of miR-495 on chemosensitivity. We also demonstrated that miR-495
      increased the intracellular CDDP accumulation and overexpression of ATP7A can
      reduce the increased drug concentration induced by miR-495. Finally, we
      discovered that there was a converse relationship between miR-495 and ATP7A
      levels in NSCLC tissues sensitive or resistant to CDDP. In conclusion, our data
      demonstrate that miR-495 regulates the multi-drug resistance by modulation of
      ATP7A expression in NSCLC and suggest that miR-495 may serve as a potential
      biomarker for the treatment of multi-drug resistant NSCLC patients with high
      ATP7A levels.

PMID- 24038380
TI  - Amyotrophic lateral sclerosis: Problems and prospects.
AB  - Amyotrophic lateral sclerosis (ALS) is a lethal degenerative disorder of
      motoneurons, which may occur concurrently with frontotemporal dementia. Genetic
      analyses of the ~10% of ALS cases that are dominantly inherited provide insight
      into ALS pathobiology. Two broad themes are evident. One, prompted by
      investigations of the SOD1 gene, is that conformational instability of proteins
      triggers downstream neurotoxic processes. The second, from studies of the TDP43,
      FUS, and C9orf72 genes, is that perturbations of RNA processing can be highly
      adverse in motoneurons. Several investigations support the concept that non
      neuronal cells (microglia, astroglia, oligodendroglia) participate in the
      degenerative process in ALS. Recent data also emphasize the importance of
      molecular events in the axon and distal motoneuron terminals. Only 1 compound,
      riluzole, is approved by the US Food and Drug Administration for ALS; several
      therapies are in clinical trials, including 2 mesenchymal stem cell trials. The
      challenges and unmet needs in ALS emphasize the importance of new research
      directions: high-throughput sequencing of large DNA sets of familial and sporadic
      ALS, which will define scores of candidate ALS genes and pathways and facilitate
      studies of epistasis and epigenetics; infrastructures for candidate gene
      validation, including in vitro and in vivo modeling; valid biomarkers that
      elucidate causative molecular events and accelerate clinical trials; and in the
      long term, methods to identify environmental toxins. The unprecedented intensity
      of research in ALS and the advent of extraordinary technologies (rapid,
      inexpensive DNA sequencing; stem cell production from skin-derived fibroblasts;
      silencing of miscreant mutant genes) bode well for discovery of innovative ALS
      therapies.

PMID- 24038381
TI  - The fatty acid amide hydrolase inhibitor oleoyl ethyl amide counteracts bladder
      overactivity in female rats.
AB  - AIMS: To study micturition and bladder overactivity in female rats after chronic
      treatment with the fatty acid amide hydrolase (FAAH) inhibitor oleoyl ethyl amide
      (OEtA). METHODS: Sprague-Dawley rats received daily subcutaneous injections of
      OEtA (0.3 mg/kg), or vehicle for 2 weeks. Cystometries, organ bath studies,
      Western blot, and immunofluorescence were then used. Expressions of FAAH,
      cannabinoid 1 and 2 receptors (CB1 and CB2), mitogen-activated protein kinase
      (MAPK), vesicular acetyl choline-transporter protein (VAChT), and calcitonin gene
      related peptide (CGRP) were evaluated. RESULTS: At baseline, OEtA-treated rats
      had higher values (P < 0.05) of micturition intervals (MI) and volumes (MV),
      bladder capacity (BC), threshold pressure, and flow pressure than vehicle
      controls. Intravesical PGE2 reduced MI, MV, and BC, and increased basal pressure
      and the area under the curve in all rats. However, these urodynamic parameters
      were altered less by intravesical PGE2 in OEtA-treated rats (P < 0.05 vs. vehicle
      controls). Compared to vehicle controls, detrusor from OEtA-treated rats had
      larger contractions to carbachol at 10-0.1 uM, but no difference in Emax was
      recorded. FAAH, CB1, CB2, VAChT, or CGRP was similarly expressed in bladders from
      all rats. In separate experiments, intravesical OEtA increased mucosal expression
      of phosphorylated MAPK. CONCLUSIONS: Chronic FAAH inhibition altered sensory
      urodynamic parameters and reduced bladder overactivity. Even if it cannot be
      excluded that OEtA may act on central nervous sensory pathways to contribute to
      these effects, the presence of FAAH and CB receptors in the bladder and
      activation of intracellular signals for CB receptors by intravesical OEtA suggest
      a local role for FAAH in micturition control.

PMID- 24038382
TI  - Automatic assignment of 1H-NMR spectra of small molecules.
AB  - A novel data-evaluation procedure for the automatic atom to peak or multiplet
      assignment of 1H-NMR spectra of small molecules has been developed using a fast
      and robust expert system. The applicability and reliability of the method are
      demonstrated by comparison of a manually assigned database of 1H-NMR spectra with
      the assignments produced by the automatic procedure. The results of this analysis
      show an excellent success ratio, indicating that this new algorithm can have a
      major impact as a time saving tool for the organic chemist. A new graphical
      feature used to illustrate both the stability and quality of the elementary
      assignments is also introduced.

PMID- 24038383
TI  - Insights into the reactivity of gold-dithiocarbamato anticancer agents toward
      model biomolecules by using multinuclear NMR spectroscopy.
AB  - Some gold(III)-dithiocarbamato derivatives of either single amino acids or
      oligopeptides have shown promise as potential anticancer agents, but their
      capability to interact with biologically relevant macromolecules is still poorly
      understood. We investigated the affinity of the representative complex
      [Au(III)Br2(dtc-Sar-OCH3)] (dtc: dithiocarbamate; Sar: sarcosine (N
      methylglycine)) with selected model molecules for histidine-, methionine-, and
      cysteine-rich proteins (that is, 1-methylimidazole, dimethylsulfide, and N-acetyl
      L-cysteine, respectively). In particular, detailed mono- and multinuclear NMR
      studies, in combination with multiple (13)C/(15)N enrichments, allowed
      interactions to be followed over time and indicated somewhat unexpected reaction
      pathways. Whereas dimethylsulfide proved to be unreactive, a sudden multistep
      redox reaction occurred in the presence of the other potential sulfur donor, N
      acetyl-L-cysteine (confirmed if glutathione was used instead). On the other hand,
      1-methylimidazole underwent an unprecedented acid-base reaction with the
      gold(III) complex, rather than the expected coordination to the metal center by
      replacing, for instance, a bromide. Our results are discussed herein and compared
      with the data available in the literature on related complexes; our findings
      confirm that the peculiar reactivity of gold(III)-dithiocarbamato complexes can
      lead to novel reaction pathways and, therefore, to new cytotoxic mechanisms in
      cancer cells.

PMID- 24038384
TI  - Declining rates of work-related overexertion back injuries among union drywall
      installers in Washington State, 1989-2008: Improved work safety or shifting of
      care?
AB  - INTRODUCTION: Construction workers are at high risk of work-related
      musculoskeletal back disorders, and research suggests medical care and costs
      associated with these conditions may be covered by sources other than workers'
      compensation (WC). Little is known about the back injury experience and care
      seeking behavior among drywall installers, a high-risk workgroup regularly
      exposed to repetitive activities, awkward postures, and handling heavy building
      materials. METHODS: Among a cohort of 24,830 Washington State union carpenters
      (1989-2008), including 5,073 drywall installers, we identified WC claims, visits
      for health care covered through union-provided health insurance and time at risk.
      Rates of work-related overexertion back injuries (defined using WC claims data)
      and health care utilization for musculoskeletal back disorders covered by private
      health insurance were examined and contrasted over time and by worker
      characteristics, stratified by type of work (drywall installation, other
      carpentry). RESULTS: Drywall installers' work-related overexertion back injury
      rates exceeded those of other carpenters (adjusted IRR 1.63, 95% CI 1.48-1.78).
      For both carpentry groups, rates declined significantly over time. In contrast,
      rates of private healthcare utilization for musculoskeletal back disorders were
      similar for drywall installers compared to other carpenters; they increased over
      time (after the mid-1990s), with increasing years in the union, and with
      increasing numbers of work-related overexertion back injuries. CONCLUSIONS:
      Observed declines over time in the rate of work-related overexertion back injury,
      as based on WC claims data, is encouraging. However, results add to the growing
      literature suggesting care for work-related conditions may be being sought
      outside of the WC system.

PMID- 24038385
TI  - Weight bias among professionals treating eating disorders: attitudes about
      treatment and perceived patient outcomes.
AB  - OBJECTIVE: This study aimed to assess weight bias among professionals who
      specialize in treating eating disorders and identify to what extent their weight
      biases are associated with attitudes about treating obese patients. METHOD:
      Participants were 329 professionals treating eating disorders, recruited through
      professional organizations that specialize in eating disorders. Participants
      completed anonymous, online self-report questionnaires, assessing their explicit
      weight bias, perceived causes of obesity, attitudes toward treating obese
      patients, perceptions of treatment compliance and success of obese patients, and
      perceptions of weight bias among other practitioners. RESULTS: Negative weight
      stereotypes were present among some professionals treating eating disorders.
      Although professionals felt confident (289; 88%) and prepared (276; 84%) to
      provide treatment to obese patients, the majority (184; 56%) had observed other
      professionals in their field making negative comments about obese patients, 42%
      (138) believed that practitioners who treat eating disorders often have negative
      stereotypes about obese patients, 35% (115) indicated that practitioners feel
      uncomfortable caring for obese patients, and 29% (95) reported that their
      colleagues have negative attitudes toward obese patients. Compared to
      professionals with less weight bias, professionals with stronger weight bias were
      more likely to attribute obesity to behavioral causes, expressed more negative
      attitudes and frustrations about treating obese patients, and perceived poorer
      treatment outcomes for these patients. DISCUSSION: Similar to other health
      disciplines, professionals treating eating disorders are not immune to weight
      bias. This has important implications for provision of clinical treatment with
      obese individuals and efforts to reduce weight bias in the eating disorders
      field.

PMID- 24038386
TI  - Esophageal-subarachnoid fistula: a case of spontaneous tension pneumocephalus in
      the setting of esophageal cancer.
AB  - BACKGROUND: Pneumocephalus occurs as a result of traumatic or iatrogenic
      violation of the dura. Tension pneumocephalus, whereby air continues to
      accumulate with no mechanism for escape, can cause significant morbidity and
      mortality. METHODS: This case report reviews the underlying pathophysiology,
      clinical presentation, diagnosis, and management of tension pneumocephalus.
      RESULTS: We present the case of a 68-year-old man who presented to the Emergency
      Department with headache thought to be the result of a newfound intracranial
      mass. After admission, he became obtunded and was found to have tension
      pneumocephalus requiring emergent evacuation. A cervical esophagus carcinoma
      caused an esophageal-subarachnoid fistula that resulted in tension pneumocephalus
      after a retching episode. CONCLUSION: This case illustrates the importance of
      considering alternative sources of pneumocephalus in the absence of more typical
      differential diagnosis.

PMID- 24038387
TI  - Hydrogen-bond cooperative effects in small cyclic water clusters as revealed by
      the interacting quantum atoms approach.
AB  - The cooperative effects of hydrogen bonding in small water clusters (H2 O)n (n=3
      6) have been studied by using the partition of the electronic energy in
      accordance with the interacting quantum atoms (IQA) approach. The IQA energy
      splitting is complemented by a topological analysis of the electron density
      (rho(r)) compliant with the quantum theory of atoms-in-molecules (QTAIM) and the
      calculation of electrostatic interactions by using one- and two-electron
      integrals, thereby avoiding convergence issues inherent to a multipolar
      expansion. The results show that the cooperative effects of hydrogen bonding in
      small water clusters arise from a compromise between: 1) the deformation energy
      (i.e., the energy necessary to modify the electron density and the configuration
      of the nuclei of the isolated water molecules to those within the water
      clusters), and 2) the interaction energy (Eint ) of these contorted molecules in
      (H2 O)n . Whereas the magnitude of both deformation and interaction energies is
      enhanced as water molecules are added to the system, the augmentation of the
      latter becomes dominant when the size of the cluster is increased. In addition,
      the electrostatic, classic, and exchange components of Eint for a pair of water
      molecules in the cluster (H2 O)n-1 become more attractive when a new H2 O unit is
      incorporated to generate the system (H2 O)n with the last-mentioned contribution
      being consistently the most important part of Eint throughout the hydrogen bonds
      under consideration. This is opposed to the traditional view, which regards
      hydrogen bonding in water as an electrostatically driven interaction. Overall,
      the trends of the delocalization indices, delta(Omega,Omega'), the QTAIM atomic
      charges, the topology of rho(r), and the IQA results altogether show how
      polarization, charge transfer, electrostatics, and covalency contribute to the
      cooperative effects of hydrogen bonding in small water clusters. It is our hope
      that the analysis presented in this paper could offer insight into the different
      intra- and intermolecular interactions present in hydrogen-bonded systems. 

PMID- 24038388
TI  - 25th anniversary article: recent advances in n-type and ambipolar organic field
      effect transistors.
AB  - The advantages of organic field-effect transistors, such as low cost, mechanical
      flexibility and large-area fabrication, make them potentially useful for
      electronic applications such as flexible switching backplanes for video displays,
      radio frequency identifications and so on. A large amount of molecules were
      designed and synthesized for electron transporting (n-type) and ambipolar organic
      semiconductors with improved performance and stability. In this review, we focus
      on the advances in performance and molecular design of n-type and ambipolar
      semiconductors reported in the past few years. 

PMID- 24038389
TI  - The DNA hypomethylating agent, 5-aza-2'-deoxycytidine, enhances tumor cell
      invasion through a transcription-dependent modulation of MMP-1 expression in
      human fibrosarcoma cells.
AB  - In diseases such as cancer, cells need to degrade the extracellular matrix (ECM)
      and therefore require high protease levels. Thus, aberrant tissue degradation is
      associated to matrix metalloproteinases (MMPs) overexpression resulting from
      different mechanisms including epigenetic events. One of the most characterized
      epigenetic mechanisms is DNA methylation causing changes in chromatin
      conformation, thereby decreasing the accessibility to the transcriptional
      machinery and resulting in a robust gene silencing. Modulation of DNA methylation
      by DNA hypomethylating agents such as 5-aza-2'-deoxycytidine (5-azadC) is widely
      used in epigenetic anticancer treatments. Here, we focus on the effects of this
      drug on the expression level of MMP-1, -2, and -9 in human HT1080 fibrosarcoma
      cells. We demonstrate that 5-azadC increases MMP expression at both mRNA and
      protein levels, and promotes invasion potential of HT1080 cells. Using broad
      spectrum and specific MMP inhibitors, we establish that MMP-1, but not MMP-2 and 
      9, plays a key role in 5-azadC-enhanced cell invasion. We show that 5-azadC
      induces MMP-1 expression through a transcriptional mechanism without affecting
      MMP-1 promoter methylation status. Finally, we demonstrate that 5-azadC treatment
      increases the nuclear levels of Sp1 and Sp3 transcription factors, and modulates
      their recruitment to the MMP-1 promoter, resulting in chromatin remodeling
      associated to 5-azadC-induced MMP-1 expression. All together, our data indicate
      that the hypomethylating agent 5-azadC modulates, mainly via Sp1 recruitment, MMP
      1 expression resulting in an increased invasive potential of HT1080 cells.

PMID- 24038390
TI  - Quality-quantity decomposition of income elasticity of U.S. hospital care
      expenditure using state-level panel data.
AB  - Economic theory suggests that income growth could lead to changes in consumption
      quantity and quality as the spending on a commodity changes. Similarly, the
      volume and quality of healthcare consumption could rise with incomes because of
      demographic changes, usage of innovative medical technologies, and other factors.
      Hospital healthcare spending is the largest component of aggregate US healthcare
      expenditures. The novel contribution of our paper is estimating and decomposing
      the income elasticity of hospital care expenditures (HOCEXP) into its quantity
      and quality components. By using a 1999-2008 panel dataset of the 50 US states,
      results from the seemingly unrelated regressions model estimation reveal the
      income elasticity of HOCEXP to be 0.427 (std. error=0.044), with about 0.391
      (calculated std. error=0.044) arising from care quality improvements and 0.035
      (std. error=0.050) emanating from the rise in usage volume. Our novel research
      findings suggest the following: (i) the quantity part of hospital expenditure is
      inelastic to income change; (ii) almost the entire income-induced rise in
      hospital expenditure comes from care quality changes; and (iii) the 0.427 income
      elasticity of HOCEXP, the largest component of total US healthcare expenditure,
      makes hospital care a normal commodity and a much stronger technical necessity
      than aggregate healthcare. Policy implications are discussed.

PMID- 24038391
TI  - Predictors of drug use in prison among women convicted of violent crimes.
AB  - BACKGROUND: Worldwide, some prisoners consume illicit drugs while in prison.
      There is now some recognition of risk factors for this among male but not female
      prisoners. AIM: The aim was to identify variables associated with drug use by
      women in prison after conviction for violent crimes. METHOD: Data were obtained
      from 315 women serving a sentence for robbery or homicide in the Penitentiary of
      Sant'Ana, Sao Paulo State, Brazil. Mainly self-report assessments of alcohol and
      drug misuse, sexual and general impulsiveness, depression, and psychosocial and
      criminological features were completed. Data were analysed using descriptive
      statistics and multivariate logistic regression. RESULTS: Thirty-five (11%) women
      reported illicit drug use in prison. Younger age, history of childhood sexual
      abuse, having committed robbery (rather than homicide), earlier onset of criminal
      activities, higher scores on sexual impulsiveness, drug-related problems prior to
      incarceration and having same-sex relationships inside prison were associated
      with a higher risk of using drugs in prison. In a multiple logistic regression,
      only prior drug history and having same-sex relationships in prison were
      independently associated with in-prison drug use. CONCLUSIONS: Illicit drug use
      in prison impairs rehabilitative goals. Identification of risk factors for this
      can help to recognise people with high treatment needs. We found that in-prison
      drug users seemed to be an exceptionally needy group, likely to have more wide
      ranging historical problems than their similar offending peers. It is essential
      to check for history of drug use outside prison. The strong association with
      active sexual behaviour in the prison highlighted another area of vulnerability,
      requiring sensitive in-prison attention to safeguard these women. Further
      research to understand the reasons for this relationship is recommended.

PMID- 24038392
TI  - Clinically significant missense variants in human GALNT3, GALNT8, GALNT12, and
      GALNT13 genes: intriguing in silico findings.
AB  - Aberrant glycosylation by N-acetylgalactosaminyl transferases (GALNTs) is a well
      described pathological alteration that is widespread in hereditary diseases,
      prominently including human cancers, familial tumoral calcinosis and hyperostosis
      hyperphosphatemia. In this study, we integrated different computational tools to
      perform the in silico analysis of clinically significant mutations (nsSNPs/single
      amino acid change) at both functional and structural levels, found in human
      GALNT3, GALNT8, GALNT12, and GALNT13 genes. From function and structure based
      insights, mutations encoding R162Q, T359K, C574G, G359D, R297W, D303N, Y396C, and
      D313N substitutions were concordantly predicted highly deleterious for relevant
      GALNTs proteins. From intriguing findings, T359K-GALNT3 was simulated with high
      contribution for disease susceptibility (tumor calcinosis) as compared to its
      partner variant T272K (Ichikawa et al. [2006] J. Clin. Endocrinol. Metab. 91:4472
      4475). Similarly, the prediction of high damaging behavior, evolutionary
      conservation and structural destabilization for C574G were proposed as major
      contributing factors to regulate metabolic disorder underlying tumor calcinosis
      and hyperostosis-hyperphosphatemia syndrome. In case of R297W-GALNT12, prediction
      of highly deleterious effect and disruption in ionic interactions were
      anticipated with reduction in enzymatic activity, associated with bilateral
      breast cancer and primary colorectal cancers. The second GALNT12 mutation (D303N)
      known splice variant-was predicted with disease severity as a result of decrease
      in charge density and buried behavior neighboring the catalytic B domain. In the
      lack of adequate in silico data about systematic characterization of clinically
      significant mutations in GALNTs genes, current study can be used as a significant
      tool to interpret the role of GALNTs reaction chemistry in disease-association
      risks in body.

PMID- 24038393
TI  - Carbene radicals in cobalt(II)-porphyrin-catalysed carbene carbonylation
      reactions; a catalytic approach to ketenes.
AB  - One-pot radicals: Cobalt(III)-carbene radicals, generated by metallo-radical
      activation of diazo compounds and N-tosylhydrazone sodium salts with cobalt(II)
      complexes of porphyrins, readily undergo radical addition to carbon monoxide,
      allowing the catalytic production of ketenes. These ketenes subsequently react
      with various amines, alcohols and imines in one-pot tandem transformations to
      produce differently substituted amides, esters and beta-lactams in good isolated
      yields. 

PMID- 24038394
TI  - Biomimetic synthesis of equisetin and (+)-fusarisetin A.
AB  - (+)-Fusarisetin A belongs to a group of acyl tetramic acid natural products that
      show potential anticancer activity. Equisetin, a biogenetically related acyl
      tetramic acid, contains the basic skeleton of (+)-fusarisetin A. We proposed that
      equisetin and (+)-fusarisetin A share a biosynthetic pathway that starts with
      naturally occurring (S)-serine and an unsaturated fatty acid. In support of this
      hypothesis, we have demonstrated that a cyclization sequence involving an
      intramolecular Diels-Alder reaction followed by a Dieckmann cyclization of
      polyenoylamino acid yielded equisetin. The aerobic oxidation of equisetin,
      promoted by either Mn(III)/O2 or a reactive oxygen species (ROS) produced by
      visible-light chemistry, gave peroxyfusarisetin, which could be easily reduced to
      (+)-fusarisetin A. We report herein detailed information on the biogenetic
      synthesis of equisetin and (+)-fusarisetin A.

PMID- 24038395
TI  - Field procedures in the Army Study to Assess Risk and Resilience in
      Servicemembers (Army STARRS).
AB  - The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is a
      multi-component epidemiological and neurobiological study of unprecedented size
      and complexity designed to generate actionable evidence-based recommendations to
      reduce US Army suicides and increase basic knowledge about determinants of
      suicidality by carrying out coordinated component studies. A number of major
      logistical challenges were faced in implementing these studies. The current
      report presents an overview of the approaches taken to meet these challenges,
      with a special focus on the field procedures used to implement the component
      studies. As detailed in the paper, these challenges were addressed at the onset
      of the initiative by establishing an Executive Committee, a Data Coordination
      Center (the Survey Research Center [SRC] at the University of Michigan), and
      study-specific design and analysis teams that worked with staff on
      instrumentation and field procedures. SRC staff, in turn, worked with the Office
      of the Deputy Under Secretary of the Army (ODUSA) and local Army Points of
      Contact (POCs) to address logistical issues and facilitate data collection. These
      structures, coupled with careful fieldworker training, supervision, and piloting,
      contributed to the major Army STARRS data collection efforts having higher
      response rates than previous large-scale studies of comparable military samples.

PMID- 24038397
TI  - Subconscious man: the basal ganglia as a target for intervention in emotional
      disorders.

PMID- 24038396
TI  - Astrocyte-enriched miR-29a targets PUMA and reduces neuronal vulnerability to
      forebrain ischemia.
AB  - Following transient forebrain ischemia, astrocytes play a key role in determining
      whether or not neurons in the hippocampal CA1 sector go on to die in a delayed
      fashion. MicroRNAs (miRNAs) are a novel class of RNAs that control gene
      expression at the post-transcriptional level and the miR-29 family is highly
      expressed in astrocytes. In this study we assessed levels of miR-29 in
      hippocampus following forebrain ischemia and found that after transient forebrain
      ischemia and short periods of reperfusion, miR-29a significantly increased in the
      resistant dentate gyrus, but decreased in the vulnerable CA1 region of the
      hippocampus. We demonstrate that miR-29a targets BH3-only proapoptotic BCL2
      family member PUMA by luciferase reporter assay and by Western blot. Comparing
      primary neuron and astrocyte cultures, and postnatal brain, we verified the
      strongly astrocytic expression of miR-29a. We further found that miR-29a mimic
      protects and miR-29a inhibitor aggravates cell injury and mitochondrial function
      after ischemia-like stresses in vitro. Lastly, by overexpressing and reducing miR
      29a we demonstrate the protective effect of miR-29a on CA1 delayed neuronal death
      after forebrain ischemia. Our data suggest that by targeting a pro-apoptotic BCL2
      family member, increasing levels of miR-29a might emerge as a strategy for
      protection against ischemia-reperfusion injury.

PMID- 24038398
TI  - Examining tumor control and toxicity after stereotactic body radiotherapy in
      locally recurrent previously irradiated head and neck cancers: implications of
      treatment duration and tumor volume.
AB  - BACKGROUND: Stereotactic body radiotherapy (SBRT) has been studied in locally
      recurrent previously-irradiated head and neck cancers; however, the optimum
      fractionation and patient selection continues to be defined. METHODS: Patients (n
      = 132) with locally recurrent head and neck cancer salvaged via SBRT +/-
      cetuximab (median, 44 Gy/5 fractions) from November 2004 to May 2011 were
      retrospectively reviewed. Disease outcomes and toxicity were analyzed by
      predictive factors including treatment duration and tumor volume. RESULTS: At a
      median 6-month follow-up (range, 0-55 months), treatment duration <14 days was
      associated with significantly improved recurrence-free survival (RFS) at the
      expense of increased late toxicity (p = .029). Tumor volume >25 cc remained a
      significant predictor of inferior survival and tumor control, and was associated
      with significantly more acute toxicity (p = .017) but no difference in late
      toxicity. CONCLUSION: SBRT +/- cetuximab achieves promising tumor control and
      survival with low rates of acute/late toxicity even for recurrences >25 cc.
      Prolongations in treatment time may decrease late toxicity at the expense of
      disease control.

PMID- 24038399
TI  - Cell lineage in vascularized bone transplantation.
AB  - BACKGROUND: The biology behind vascularized bone allotransplantation remains
      largely unknown. We aim to study cell traffic between donor and recipient
      following bone auto-, and allografting. METHODS: Vascularized femoral
      transplantation was performed with arteriovenous bundle implantation and short
      term immunosuppression. Twenty male Piebald Virol Glaxo (PVG; RT1(c) ) rats
      received isotransplants from female PVG (RT1(c) ) rats and 22 male PVG rats
      received allografts from female Dark Agouti rats (DA, RT1(a) ), representing a
      major histocompatibility mismatch. Both groups were randomly analyzed at 4 or 18
      weeks. Bone remodeling areas (inner and outer cortical samples) were labeled and
      laser capture microdissected. Analysis of sex-mismatch genes by real-time reverse
      transcription-polymerase chain reaction provided the relative Expression Ratio
      (rER) of donor (female) to recipient (male) cells. RESULTS: The rER was 0.456 +/-
      0.266 at 4 weeks and 0.749 +/- 0.387 at 18 weeks (p = 0.09) in allotransplants.
      In isotransplants, the rER was 0.412 +/- 0.239 and 0.467 +/- 0.252 at 4 and 18
      weeks, respectively (p = 0.21). At 4 weeks, the rER at the outer cortical area of
      isotransplants was significantly lower in isotransplants as compared with
      allotransplants (0.247 +/- 0.181 vs. 0.549 +/- 0.184, p = 0.007). Cells in the
      inner and outer cortical bone remodeling areas in isotransplants were mainly
      donor derived (rER < 0.5) at 18 weeks, whereas allotransplants contained mainly
      recipient-derived cells (rER > 0.5) at 18 weeks. CONCLUSIONS: Applying novel
      methodology, we describe detailed cell traffic in vascularized bone transplants,
      elaborating our comprehension on bone transplantation.

PMID- 24038400
TI  - The roles of counterion and water in a stereoselective cysteine-catalyzed Rauhut
      Currier reaction: a challenge for computational chemistry.
AB  - The stereoselective Rauhut-Currier (RC) reaction catalyzed by a cysteine
      derivative has been explored computationally with density functional theory (M06
      2X). Both methanethiol and a chiral cysteine derivative were studied as
      nucleophiles. The complete reaction pathway involves rate-determining elimination
      of the thiol catalyst from the Michael addition product. The stereoselective
      Rauhut-Currier reaction, catalyzed by a cysteine derivative as a nucleophile, has
      also been studied in detail. This reaction was experimentally found to be
      extremely sensitive to the reaction conditions, such as the number of water
      equivalents and the effect of potassium counterion. The E1cB process for catalyst
      elimination has been explored computationally for the eight possible
      stereoisomers. The effect of explicit water solvation and the presence of
      counterion (either K(+) or Na(+) ) has been studied for the lowest energy
      enantiomer pair (1S, 2R, 3S)/(1R, 2S, 3R). 

PMID- 24038401
TI  - Model building in nonproportional hazard regression.
AB  - Recent developments of statistical methods allow for a very flexible modeling of
      covariates affecting survival times via the hazard rate, including also the
      inspection of possible time-dependent associations. Despite their immediate
      appeal in terms of flexibility, these models typically introduce additional
      difficulties when a subset of covariates and the corresponding modeling
      alternatives have to be chosen, that is, for building the most suitable model for
      given data. This is particularly true when potentially time-varying associations
      are given. We propose to conduct a piecewise exponential representation of the
      original survival data to link hazard regression with estimation schemes based on
      of the Poisson likelihood to make recent advances for model building in
      exponential family regression accessible also in the nonproportional hazard
      regression context. A two-stage stepwise selection approach, an approach based on
      doubly penalized likelihood, and a componentwise functional gradient descent
      approach are adapted to the piecewise exponential regression problem. These three
      techniques were compared via an intensive simulation study. An application to
      prognosis after discharge for patients who suffered a myocardial infarction
      supplements the simulation to demonstrate the pros and cons of the approaches in
      real data analyses.

PMID- 24038402
TI  - Deuterium isotope effects on 13C chemical shifts of negatively charged NH...N
      systems.
AB  - Deuterium isotope effects on (13)C chemical shifts are investigated in anions of
      1,8-bis(4-toluenesulphonamido)naphthalenes together with N,N-(naphthalene-1,8
      diyl)bis(2,2,2-trifluoracetamide) all with bis(1,8-dimethylamino)napthaleneH(+)
      as counter ion. These compounds represent both "static" and equilibrium cases.
      NMR assignments of the former have been revised. The NH proton is deuteriated.
      The isotope effects on (13)C chemical shifts are rather unusual in these strongly
      hydrogen bonded systems between a NH and a negatively charged nitrogen atom. The
      formal four-bond effects are found to be negative indicating transmission via the
      hydrogen bond. In addition, unusual long range effects are seen. Structures, (1)H
      and (13)C NMR chemical shifts and changes in nuclear shieldings upon deuteriation
      are calculated using density functional theory methods.

PMID- 24038404
TI  - Carbon fiber aerogel made from raw cotton: a novel, efficient and recyclable
      sorbent for oils and organic solvents.
AB  - Twisted carbon fiber (TCF) aerogel with good selective sorption is produced in
      large scale by using raw cotton as the precursor. TCF aerogel shows highly
      efficient sorption of organic liquids (pump oil: up to 192 times its own weight;
      chloroform: up to 115 times its own weight). Moreover, it could be regenerated
      many times without decrease of sorption capacity by distillation, combustion or
      squeezing, which depends on the type of pollutants. 

PMID- 24038403
TI  - Correlation between safety climate and contractor safety assessment programs in
      construction.
AB  - BACKGROUND: Contractor safety assessment programs (CSAPs) measure safety
      performance by integrating multiple data sources together; however, the
      relationship between these measures of safety performance and safety climate
      within the construction industry is unknown. METHODS: Four hundred and one
      construction workers employed by 68 companies on 26 sites and 11 safety managers
      employed by 11 companies completed brief surveys containing a nine-item safety
      climate scale developed for the construction industry. CSAP scores from
      ConstructSecure, Inc., an online CSAP database, classified these 68 companies as
      high or low scorers, with the median score of the sample population as the
      threshold. Spearman rank correlations evaluated the association between the CSAP
      score and the safety climate score at the individual level, as well as with
      various grouping methodologies. In addition, Spearman correlations evaluated the
      comparison between manager-assessed safety climate and worker-assessed safety
      climate. RESULTS: There were no statistically significant differences between
      safety climate scores reported by workers in the high and low CSAP groups. There
      were, at best, weak correlations between workers' safety climate scores and the
      company CSAP scores, with marginal statistical significance with two groupings of
      the data. There were also no significant differences between the manager-assessed
      safety climate and the worker-assessed safety climate scores. CONCLUSIONS: A CSAP
      safety performance score does not appear to capture safety climate, as measured
      in this study. The nature of safety climate in construction is complex, which may
      be reflective of the challenges in measuring safety climate within this industry.
      Am. J. Ind. Med. 56:1463-1472, 2013. (c) 2013 Wiley Periodicals, Inc.

PMID- 24038405
TI  - Urodynamic results, clinical efficacy, and complication rates of sacral
      intradural deafferentation and sacral anterior root stimulation in patients with
      neurogenic lower urinary tract dysfunction resulting from complete spinal cord
      injury.
AB  - AIMS: To investigate the outcome and complications of sacral deafferentation
      (SDAF) and sacral anterior root stimulation (SARS) in patients with neurogenic
      lower urinary tract dysfunction (NLUTD) resulting from complete spinal cord
      injury (SCI). METHODS: Retrospective chart analysis of 137 patients who underwent
      SDAF/SARS at a single institution. Patients were categorized as being at risk of
      renal damage when the maximum detrusor pressure was >40 cmH2 O or detrusor
      compliance was <20 ml/cmH2 O. RESULTS: After a mean follow-up time of 14.8 +/-
      5.3 years, SDAF/SARS treatment significantly (P < 0.001) reduced the number of
      patients suffering from elevated detrusor pressure from 65 to 2, and from low
      detrusor compliance from 62 to 13, respectively. Mean bladder capacity
      significantly (P < 0.001) improved from 272.4 +/- 143.0 to 475.0 +/- 82.7 ml. The
      mean number of symptomatic UTI also decreased significantly (P < 0.001) from 6.2
      +/- 4.5 to 2.5 +/- 2.6 per year. The number of patients suffering from
      incontinence had significantly (P < 0.001) decreased from 70 to 44. At the last
      follow-up visit, 107 (78.1%) patients were still using the stimulator. A total of
      84 complications requiring surgical revision were observed. Defects of the
      stimulator cables or the receiver plate were the most common events (n = 38). The
      retrospective design pertains to the limitations of the study. CONCLUSIONS:
      Sacral deafferentation and SARS are an effective treatment option for refractory
      NLUTD in patients with complete SCI, despite a substantial long-term complication
      rate.

PMID- 24038406
TI  - Genetic variations in base excision repair pathway and risk of bladder cancer: a
      case-control study in the United States.
AB  - Base excision repair (BER) is one of the major cellular DNA repair pathways that
      repairs small isolated foci of DNA damage including reduced or oxidized single
      bases or fragments and small, non-bulky adducts. Genetic variations in BER genes
      may affect DNA repair capacity and increase susceptibility to bladder cancer. In
      a case-control study of 801 bladder cancer patients and 801 matched controls, we
      evaluated the associations of 167 single nucleotide polymorphisms (SNPs) from 19
      genes of the BER pathway with the risk of bladder cancer. In individual SNP
      analysis, 13 SNPs in 10 BER pathway genes were significantly associated with
      bladder cancer risk. The most significant SNP was rs2029167 in the SMUG1 gene.
      The homozygous variant GG genotype was associated with a 1.42-fold increased risk
      of bladder cancer (95% confidence interval [CI], 1.11-1.82, P=0.005). Cumulative
      effect analysis showed joint effects of increased risk of bladder cancer with
      increasing number of unfavorable genotypes in patients. Classification and
      regression tree analysis further revealed high-order gene-gene interactions and
      categorized the study subjects into low-, medium-low-, medium-high-, and high
      risk groups. Compared with the low-risk group, the odds ratio for medium-low-,
      medium-high-, and high-risk group was 1.83 (95% CI: 1.23-2.72), 2.61 (95% CI:
      1.79-3.80), and 3.05 (95% CI: 2.08-4.46), respectively (P for trend<0.001). Our
      results suggest that genetic variations in BER pathway genes modulate the risk of
      bladder cancer individually and jointly.

PMID- 24038407
TI  - Synthesis and biological activity of 7,8,9-trideoxy- and 7R desTHP-peloruside A.
AB  - The stereoselective syntheses of 7,8,9-trideoxypeloruside A (4) and a monocyclic
      peloruside A analogue lacking the entire tetrahydropyran moiety (3) are
      described. The syntheses proceeded through the PMB-ether of an omega-hydroxy beta
      keto aldehyde as a common intermediate which was elaborated into a pair of
      diastereomeric 1,3-syn and -anti diols by stereoselective Duthaler-Hafner
      allylations and subsequent 1,3-syn or anti reduction. One of these isomers was
      further converted into a tetrahydropyran derivative in a high-yielding Prins
      reaction, to provide the precursor for bicyclic analogue 4. Downstream steps for
      both syntheses included the substrate-controlled addition of a vinyl lithium
      intermediate to an aldehyde, thus connecting the peloruside side chain to C15
      (C13) of the macrocyclic core structure in a fully stereoselective fashion. In
      the case of monocyclic 3 macrocyclization was based on ring-closing olefin
      metathesis (RCM), while bicyclic 4 was cyclized through Yamaguchi-type
      macrolactonization. The macrolactonization step was surprisingly difficult and
      was accompanied by extensive cyclic dimer formation. Peloruside A analogues 3 and
      4 inhibited the proliferation of human cancer cell lines in vitro with micromolar
      and sub-micromolar IC50 values, respectively. The higher potency of 4 highlights
      the importance of the bicyclic core structure of peloruside A for nM biological
      activity. 

PMID- 24038408
TI  - Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear
      accelerator-based intensity-modulated radiation therapy with helical tomotherapy.
AB  - BACKGROUND: In comparison to sliding-window intensity-modulated radiation therapy
      (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar
      locoregional control and, at the same time, decrease the parotid gland dose, thus
      leading to a xerostomia reduction. METHODS: The association between radiation
      techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119
      patients with advanced oropharyngeal carcinoma treated with concurrent
      chemoradiation using sw-IMRT (n = 59) or HT (n = 60). RESULTS: Ipsilateral and
      contralateral parotid mean doses were significantly lower for patients treated
      with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy
      contralaterally. The incidence of grade >=2 xerostomia was significantly lower in
      the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51%
      at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was
      strongly associated to a lower incidence of grade >=2 xerostomia at 6, 12, and 24
      months. CONCLUSION: This retrospective series suggests that using HT can better
      spare the parotid glands while respecting quantitative analysis of normal tissue
      effects in the clinic (QUANTEC)'s criteria.

PMID- 24038409
TI  - Has increased body weight made driving safer?
AB  - We develop a model of alcohol consumption that incorporates the negative
      biological relationship between body mass and inebriation conditional on total
      alcohol consumption. Our model predicts that the elasticity of inebriation with
      respect to weight is equal to the own-price elasticity of alcohol, consistent
      with body mass increasing the effective price of inebriation. Given that alcohol
      is generally considered price inelastic, this result implies that as individuals
      gain weight, they consume more alcohol but become less inebriated. We test this
      prediction and find that driver blood alcohol content (BAC) is negatively
      associated with driver weight. In fatal accidents with driver BAC above 0.10, the
      driver was 7.8 percentage points less likely to be obese than drivers in fatal
      accidents that did not involve alcohol. This relationship is not explained by
      driver attributes (age and sex), driver behaviors (speed and seatbelt use),
      vehicle attributes (weight class, model year, and number of occupants), or
      accident context (county of accident, time of day, and day of week).

PMID- 24038410
TI  - Case formulation in personality disordered offenders - a Delphi survey of
      professionals.
AB  - BACKGROUND: Case formulation (CF) integrates information about an individual to
      conceptualise the factors causing and maintaining their current difficulties. It
      is a core clinical skill for both psychologists and psychiatrists. The recent UK
      government Offender Personality Disorder (PD) Strategy proposes a key role of
      probation staff in CF. Yet, CF in forensic settings has only recently received
      research attention, and it is unclear how and by whom it ought to be performed.
      AIMS: This study aimed to gain consensus on the key characteristics of CF in PD
      offenders. METHODS: We conducted an electronic Delphi survey of experts with a
      background in psychology or psychiatry. RESULTS: Consensus was achieved on who
      can perform CF, who it should be offered to and the benefits, process,
      theoretical models and content of CF. A cognitive-behavioural therapy or schema
      focused model was felt to be best suited to inform CF in PD offenders. No
      agreement was achieved on the assessment of quality of CF. DISCUSSION: Our
      findings support the government's PD strategy in that experts agreed that CF
      could be performed by professionals other than psychiatrists and psychologists.
      However, more research is needed on how to best assess the quality of CF and its
      utility in determining treatment pathways. CLINICAL IMPLICATIONS: It may be
      possible for probation staff to take on a more active role in CF for PD offenders
      using a cognitive-behavioural or schema-focused model. However, a significant
      amount of training will be required for probation staff to acquire the relevant
      skills.

PMID- 24038411
TI  - Schwann cell-derived exosomes enhance axonal regeneration in the peripheral
      nervous system.
AB  - Axonal regeneration in the peripheral nervous system is greatly supported by
      Schwann cells (SCs). After nerve injury, SCs dedifferentiate to a progenitor-like
      state and efficiently guide axons to their original target tissues. Contact and
      soluble factors participate in the crosstalk between SCs and axons during axonal
      regeneration. Here we show that dedifferentiated SCs secrete nano-vesicles known
      as exosomes which are specifically internalized by axons. Surprisingly, SC
      derived exosomes markedly increase axonal regeneration in vitro and enhance
      regeneration after sciatic nerve injury in vivo. Exosomes shift the growth cone
      morphology to a pro-regenerating phenotype and decrease the activity of the
      GTPase RhoA, involved in growth cone collapse and axon retraction. Altogether,
      our work identifies a novel mechanism by which SCs communicate with neighboring
      axons during regenerative processes. We propose that SC exosomes represent an
      important mechanism by which these cells locally support axonal maintenance and
      regeneration after nerve damage.

PMID- 24038412
TI  - Evaluation of warfarin management with international normalized ratio self
      testing and online remote monitoring and management plus low-dose vitamin k with
      genomic considerations: a pilot study.
AB  - STUDY OBJECTIVES: As better international normalized ratio (INR) control and self
      testing reduce events in warfarin-treated patients, and vitamin K supplementation
      may improve INR control, our primary objective was to evaluate the effect of a
      system combining frequent INR self-testing with online remote monitoring and
      management (STORM2) and low-dose vitamin K supplementation on INR control; our
      secondary objectives were to assess the impact of STORM2 on clinician time and to
      evaluate the influence of pharmacogenomics on INR stability and warfarin dose
      after vitamin K supplementation. DESIGN: Prospective pre- and postintervention
      study. SETTING: Freestanding clinical research center. PATIENTS: Fifty-five
      patients treated with long-term warfarin therapy who were referred from four
      anticoagulation clinics and seven medical practices. INTERVENTION: All patients
      performed weekly INR self-testing and received vitamin K 100 ug/day and online
      anticoagulation management for 1 year. MEASUREMENTS AND MAIN RESULTS: INR control
      and time required for anticoagulation management were assessed, and an analysis
      of warfarin dosing and INR stability by genetic polymorphism subgroup (vitamin K
      epoxide reductase complex 1 [VKORC1] and cytochrome P450 2C9 isoenzyme) was
      performed; vitamin K product content was also analyzed. The percentage of time
      that the INR is within the time in therapeutic range (TTR) improved from 56%
      before the intervention to 81% after the intervention (p<0.0001), and time spent
      at extreme INR values of lower than 1.5 or higher than 5 was reduced from 3.1% to
      0.4% (p=0.01). Clinician time was less than 10 minutes per four patient visits
      per month. Genetic polymorphisms did not correlate with INR stability or the
      increase in warfarin dose after vitamin K supplementation. The content of the
      vitamin K product, however, was only 34-76% of the labeled amount. Patients with
      the GG VKORC1 genotype required a higher warfarin dose than predicted by the
      genomic-based dosing chart in the warfarin package insert. CONCLUSION: The 25%
      point improvement in TTR with STORM2 is a greater improvement than reported
      previously with other efforts to improve TTR. STORM2 required a minimum amount of
      clinician time. Pharmacogenomics were not predictive of improved INR control or
      the magnitude of the warfarin dose after vitamin K supplementation, although the
      content of the product was unreliable. Patients with the GG VKORC1 genotype
      required a higher warfarin dose than predicted by the product information. The
      potential clinical impact of improved INR control with this method warrants
      comparisons with conventionally managed warfarin and with the new oral
      anticoagulants.

PMID- 24038414
TI  - Effect and possible mechanism of network between microRNAs and RUNX2 gene on
      human dental follicle cells.
AB  - To investigate whether crosstalk between RUNX2 and miRNAs is involved in tooth
      eruption regulated by dental follicle cells (DFCs) and the possible molecular
      mechanism. Blood samples and embedded dental follicles were collected from
      patients with cleidocranial dysplasia, and RUNX2 gene mutations were analyzed,
      then RUNX2(+/m) DFCs were isolated and identified. The characteristics of
      RUNX2(+/m) DFCs were analyzed. The differential expression of miRNAs was detected
      between the RUNX2(+/m) DFCs and RUNX2(+/+) DFCs by microarray, and target genes
      were predicted by miRGen. miR-146a was chosen for further investigation, and its
      effects in DFCs were analyzed by transfecting its mimics and inhibitors, and
      expression of genes involved in tooth eruption were detected. A novel insertion
      mutation (c.309_310insTG) of RUNX2 gene was identified which had an effect on the
      characteristics of DFCs. Compared with the RUNX2(+/+) DFCs, there were 69
      microRNAs more than twofold up-regulated and 54 microRNAs more than twofold down
      regulated in the RUNX2(+/m) DFCs. Among these, miR-146a decreased significantly
      in RUNX2(+/m) DFCs, and expression of RUNX2, CSF-1, EGFR, and OPG was
      significantly altered when miR-146a was overexpressed or inhibited. RUNX2 gene
      mutation contributes to the characteristic change of DFCs, and the crosstalk
      between RUNX2 gene and miRNAs may be one of the key regulatory mechanisms of
      differentiation of DFCs.

PMID- 24038415
TI  - Delayed distally based sural flap with temporary venous supercharging.
AB  - The distally based sural flap has become popular for reconstruction of the foot
      and leg. However, this flap often fails due to venous congestion. In this report,
      we developed a new modification of the distally based sural flap. The procedure
      comprised three stages. In the first stage, the flap was raised cephalad to the
      midpoint of the posterior aspect of the leg, involving reanastomosis of the short
      saphenous vein (SSV) at the proximal end of the flap. In the second stage,
      ligature of the SSV was performed. In the third stage, the entire flap was
      raised. We treated eight patients with the flap. All flaps survived completely.
      Duplex scanning indicated that venous drainage of the flap was provided by the
      tenuous venae comitantes (VCs) surrounding the SSV. Reanastomosis of the SSV may
      prevent rapid venous overloading of the VCs. Our new modification may be useful
      to avoid venous congestion.

PMID- 24038413
TI  - Energy failure: does it contribute to neurodegeneration?
AB  - Energy failure from mitochondrial dysfunction is proposed to be a central
      mechanism leading to neuronal death in a range of neurodegenerative diseases.
      However, energy failure has never been directly demonstrated in affected neurons
      in these diseases, nor has it been proved to produce degeneration in disease
      models. Therefore, despite considerable indirect evidence, it is not known
      whether energy failure truly occurs in susceptible neurons, and whether this
      failure is responsible for their death. This limited understanding results
      primarily from a lack of sensitivity and resolution of available tools and assays
      and the inherent limitations of in vitro model systems. Major advances in these
      methodologies and approaches should greatly enhance our understanding of the
      relationship between energy failure, neuronal dysfunction, and death, and help us
      to determine whether boosting bioenergetic function would be an effective
      therapeutic approach. Here we review the current evidence that energy failure
      occurs in and contributes to neurodegenerative disease, and consider new
      approaches that may allow us to better address this central issue.

PMID- 24038416
TI  - Formation and dynamic behavior of mono- and bimetallic cadmium(II) porphyrin
      complexes: allosteric control of coupled intraligand metal migrations.
AB  - The complexation behavior of a bis-strapped porphyrin ligand (1) towards Cd(II)
      has been investigated by (1)H and (113)Cd NMR spectroscopy with the help of X-ray
      diffraction structures. The presence of an overhanging carboxylic acid group on
      each side of the macrocycle is responsible for the instantaneous insertion of the
      metal ion(s) at room temperature, and allows the formation of bimetallic species
      with unusual coordination modes at the origin of unique dynamic behaviors. In the
      absence of base, a C2-symmetric bimetallic complex (1Cd2 ) is readily formed, in
      which the porphyrin acts as a bridging ligand. Both Cd(II) ions are bound to the
      N core and to a COO(-) group of a strap. In contrast, the presence of a base
      induces a two-step binding process with the successive formation of mono and
      bimetallic species (1(Cd) and 1(Cd).CdOAc). Formally, a Cd(II) ion is first
      inserted into the N core and experiences a strong out-of-plane (OOP) displacement
      due to the binding of an overhanging carbonyl group in an apical position. A
      second Cd(II) ion then binds exclusively to the strap on the opposite side, in a
      so-called hanging-atop (HAT) coordination mode. These two complexes display a
      fluxional behavior that relies on intraligand migration processes of the metal
      ion(s). In 1(Cd), the Cd(II) ion exchanges between the two equivalent overhanging
      apical ligands by funneling through the porphyrin ring. In 1(Cd).CdOAc, the two
      Cd(II) ions exchange their coordination mode (HAT<->OOP) in a concerted way while
      staying on their respective side of the macrocycle, in a so-called Newton's
      cradle-like motion. The intramolecular pathway was notably evidenced by variable
      temperature (113) Cd heteronuclear NMR experiments. This coupled motion of the
      Cd(II) cations is under allosteric control; the addition of an acetate anion (the
      allosteric effector) to the "resting" C2-symmetric complex 1Cd2 affords the
      dissymmetric complex 1(Cd).CdOAc and triggers equilibrium between its two
      degenerate states. The rate of the swinging motion further depends on the
      concentration of AcO(-), with a higher concentration leading to a slower motion.
      As compared with the related Pb(II) and Bi(III) bimetallic complexes, the
      Newton's cradle-like motion proceeds faster with the smaller Cd(II) ion. These
      results open the way to novel multistable devices and switches.

PMID- 24038417
TI  - Angular-resolved magnetometry beyond triclinic crystals: out-of-equilibrium
      studies of Cp*ErCOT single-molecule magnet.
AB  - Angular-resolved single-crystal magnetometry is a key tool to characterise
      lanthanide-based materials with low symmetry, for which conjectures based on
      idealised geometries can be totally misleading. Unfortunately the technique is
      strictly successful only for triclinic structures, thus reducing significantly
      its application. By collecting out-of-equilibrium magnetisation data the
      technique was extended to the orthorhombic organometallic Cp*ErCOT single
      molecule magnet (SMM), thus allowing for the first time the reconstruction of the
      molecular anisotropy tensor notwithstanding the two molecular orientations in the
      crystal lattice. The results, flanked by state-of-the-art ab initio calculations,
      confirmed the expected orientation of the molecular easy axis of magnetisation
      and thus validated the synthetic strategy based on organometallic complexes of a
      single lanthanide ion. 

PMID- 24038418
TI  - Selective-area van der Waals epitaxy of topological insulator grid nanostructures
      for broadband transparent flexible electrodes.
AB  - Broadband transparent electrodes based on a two-dimensional grid of topological
      insulator Bi2Se3 are synthesized by a facile selective-area van der Waals epitaxy
      method. These two-dimensional grid electrodes exhibit high uniformity over large
      area, outstanding mechanical durability, and excellent chemical resistance to
      environmental perturbations. Remarkably, the topological grid electrode has high
      transmittance of more than 85% from the visible to the near-infrared region.

PMID- 24038419
TI  - Synthesis of shape-persistent macrocycles with three 1,8-diazaanthracene units
      and their packing in the single crystal.
AB  - The synthesis of four shape-persistent macrocycles with three 1,8-diazaanthracene
      units each is reported (2,3 a-3 c). For two of them single crystals could be
      obtained and the structures in the crystal be solved. The structures reveal that
      macrocycle 2 self-dimerizes in the solid state; surprisingly it also forms a
      stable dimer in solution. The reason for this is seen in unusually efficient
      dispersion interactions as a consequence of the large contact areas in the dimer.
      All macrocycles are assessed as to their applicability in lateral polymerizations
      in the single crystal as well as in solution.

PMID- 24038420
TI  - Role of Sp5 as an essential early regulator of neural crest specification in
      xenopus.
AB  - BACKGROUND: The neural crest (NC) is a multipotent embryonic cell population,
      which is induced by an integration of secreted signals including BMP, Wnt, and
      FGF and, subsequently, NC cell fates are specified by a regulatory network of
      specific transcription factors. This study was undertaken to identify a role of
      Sp5 transcription factor in vertebrates. RESULTS: Xenopus Sp5 is expressed in the
      prospective neural crest regions from gastrulation through the tadpole stages in
      early development. Knockdown of Sp5 caused severe defects in craniofacial
      cartilage, pigmentation, and dorsal fin. Gain- and loss-of-function of Sp5 led to
      up- and down-regulation of the expression of NC markers in the neural fold,
      respectively. In contrast, Sp5 had no effect on neural induction and patterning.
      Sp5 regulated the expression of neural plate border (NPB) specifiers, Msx1 and
      Pax3, and these regulatory factors recovered the expression of NC marker in the
      Sp5-deficient embryos. Depletion of Sp5 impaired NC induction by Wnt/beta-catenin
      or FGF signal, whereas its co-expression rescued NC markers in embryos in which
      either signal was blocked. CONCLUSIONS: These results suggest that Sp5 functions
      as a critical early factor in the genetic cascade to regulate NC induction
      downstream of Wnt and FGF pathways.

PMID- 24038421
TI  - Controlled heterocyclization/cross-coupling domino reaction of beta,gamma
      allendiols and alpha-allenic esters: method and mechanistic insight for the
      preparation of functionalized buta-1,3-dienyl dihydropyrans.
AB  - Starting from beta,gamma-allendiols and alpha-allenic acetates, a chemo- and
      regiocontrolled palladium-catalyzed methodology has provided access to
      enantiopure 3,6-dihydropyrans that bear a buta-1,3-dienyl moiety. Thus, it has
      been demonstrated for the first time that the preparation of six-membered
      heterocycles through cross-coupling reactions of two different allenes can be
      accomplished. These heterocyclization/cross-coupling reactions have been
      developed experimentally and their mechanisms have additionally been investigated
      by a computational study. 

PMID- 24038422
TI  - Latent class models for medical diagnostic tests in multicenter trials.
AB  - Medical diagnostic tests must enjoy appropriate validity and high reliability in
      order to qualify as adequate assessment tools. Without a gold standard test,
      available medical diagnostic tests are not perfect; hence, the reliability of
      such tests must be evaluated precisely. Kappa coefficient statistics are often
      utilized to assess reliability of tests when there are two or more medical
      diagnostic tests. However, the statistics are imprecise for a typical case when
      the prevalence rate of a target disease is unknown. Although latent class models
      could be used to assess reliability, the models cannot estimate reliability in
      the case of two tests, due to unidentifiability or the lack of degrees of
      freedom. An alternative approach to assess reliability for the case of two tests
      is stratifying a two-by-two contingency table under the assumption that
      sensitivities and specificities between the two tests be equal over all strata
      and that prevalence rates in the strata be different from each other. Because
      stratification is basically a multi-sample analysis, it should not be applied to
      the situation where subsamples (i.e., centers) are randomly selected from a
      larger population. In this article, a type of mixed-effect model is proposed to
      evaluate the reliability of two tests for trials in randomly selected multiple
      centers. Several types of distributions for prevalence rates over subpopulations
      are considered. Simulation studies show that our proposed method performs nicely.
      Analysis of real data is also reported.

PMID- 24038423
TI  - Dietary fat without body weight gain increases in vivo MCF-7 human breast cancer
      cell growth and decreases natural killer cell cytotoxicity.
AB  - High-calorie (HC) diet contributes to the increased incidence of obesity, which
      is a risk factor for breast cancer in postmenopausal women, and in particular for
      estrogen receptor (ER) positive tumors. This study investigated whether an HC
      diet increases human ER-positive breast cancer progression and modulates natural
      killer (NK) cell functions. Four-week-old female BALB/c athymic nude mice were
      fed a HC diet (5320 kcal/kg) or standard calorie diet (SC, 2820 kcal/kg) for 6
      mo. After 5 mo, the mice were randomly implanted with MCF-7 breast cancer cells
      (SCT and HCT) or received an isovolumic injection (SC and HC) in both inguinal
      fat pads. Tumor growth was greater in the HCT group than in the SC group without
      change in body weight. The HC diet decreased the tumor expression of genes
      involved in the citrate cycle and in adiponectin and lipid metabolism but
      increased that of genes controlling glycolysis and angiogenesis. The tumor
      expression level of Ki67 was increased while that of the cleaved caspase 3 and
      the ER-beta and progesterone receptors was reduced. Tumor development in response
      to the HC diet was associated with smaller numbers and lower cytotoxicity of
      splenic NK cells. These results indicate that an HC diet without body weight gain
      increases ER-positive breast cancer cell proliferation and reduces tumor
      apoptosis. The underlying mechanisms might involve a downexpression of tumor
      hormonal receptor and reduced NK cell functions, and might also result in the
      regulation of genes involved in several cellular functions.

PMID- 24038424
TI  - Correlation of substituted aromatic beta-diketones' characteristic protons
      chemical shifts with Hammett substituent constants.
AB  - Influence of dibenzoylmethane's substituents in meta and para positions on
      chemical shift values of tautomers' characteristic protons was investigated in
      four solvents with (1)H NMR spectroscopy: acetone-d(6), benzene-d(6), CDCl(3) and
      deuterated dimethyl sulfoxide (DMSO-d(6)). It was proved that the influence of
      substituents on chemical shifts strongly depends on the kind of the solvent; the
      greatest changes were observed in benzene-d6 and the smallest in CDCl(3). In
      acetone-d(6) and DMSO-d(6), the influence of substituents on chemical shifts is
      similar and the most regular. It allowed a fair correlation of chemical shifts of
      para-substituted dibenzoylmethane derivatives' characteristic protons with
      Hammett substituent constants in these solvents. In CDCl(3), characteristic
      protons' chemical shifts were near (1)H NMR spectroscopy measurement error
      limits, and, therefore, correlation with Hammett substituent constants in this
      solvent was unsatisfactory. In benzene, although the changes of chemical shifts
      are the most evident, the changes are also the most irregular, and, therefore,
      correlation in this solvent failed completely. Results of meta-substituted
      derivatives were much more irregular, and their correlation with Hammett
      substituent constants was poor in all investigated solvents.

PMID- 24038425
TI  - Impact of a new method of warfarin management on patient satisfaction, time, and
      cost.
AB  - STUDY OBJECTIVE: International normalized ratio self-testing with online remote
      monitoring and management (STORM2) is an alternative to anticoagulation clinic
      management, but the patient's perspective of this method has not been evaluated
      in the United States; thus we sought to evaluate the impact of STORM2 on patient
      satisfaction, time, and cost. DESIGN: Prospective pre- and postintervention
      study. SETTING: Freestanding clinical research center. PATIENTS: Forty-three
      patients treated with long-term warfarin therapy and monitored initially in the
      anticoagulation clinic setting and then with STORM2, referred from 11 medical
      practices. INTERVENTION: Patients were asked to complete a survey and the Duke
      Anticoagulation Satisfaction Scale (DASS) before (at baseline) and after at least
      3 months of STORM2 (at follow-up). MEASUREMENTS AND MAIN RESULTS: Patient
      satisfaction and time were assessed by survey and the DASS. Costs were measured
      from the patient's perspective. Overall 90% of responders preferred STORM2 to
      traditional clinic management. The DASS questions indicated that patients were
      more satisfied with their anticoagulation treatment and more likely to recommend
      oral anticoagulation to a friend after experiencing STORM2. In addition, patients
      found STORM2 to be less complicated and more convenient than traditional clinic
      management. For each traditional monthly visit, patients drove 20 miles and
      expended a total of 1.8 hours; using 55c/mile for mileage reimbursement and
      $15/hour for lost wages, the cost for each visit was $38. The total cost for four
      STORM2 visits per month was $10, for a net savings of $28 per patient per month.
      A total of 76% of patients were willing to pay additional money to eliminate a
      monthly clinic visit. CONCLUSION: STORM2 is more convenient, less complicated,
      preferred by patients, and saves patients time and money compared with clinic
      management.

PMID- 24038426
TI  - The first year of behavioral development and maternal care of beluga
      (Delphinapterus leucas) calves in human care.
AB  - The current study provides additional information for the behavioral development
      and maternal care of belugas or white whales (Delphinapterus leucas) in the care
      of humans. The behaviors and mother-calf interactions of two female beluga calves
      were recorded from birth to 12 months as part of a longitudinal study of beluga
      behavioral development. As expected, the primary calf activity for both calves
      involved swimming with their mothers. The calves initiated the majority of the
      separations from and reunions with their mothers and exhibited early bouts of
      independence. Both mothers bonded with their calves and displayed similar
      maternal care behaviors but exhibited different behavioral patterns. Despite
      differences in social groupings, housing, and physical health, the two female
      belugas followed the behavioral development of beluga calves observed previously.

PMID- 24038427
TI  - Risk of severe and refractory postoperative nausea and vomiting in patients
      undergoing diep flap breast reconstruction.
AB  - BACKGROUND: Postoperative nausea and vomiting (PONV) are commonly feared after
      general anesthesia and can impact results. The primary aim of our study was to
      examine incidence and severity of PONV by investigating complete response, or
      absence of PONV, to prophylaxis used in patients undergoing DIEP flaps. Our
      secondary aims were definition of the magnitude of risk, state of the art of
      interventions, clinical sequelae of PONV, and interaction between these
      variables, specifically for DIEP patients. METHODS: A retrospective chart review
      occurred for 29 patients undergoing DIEP flap breast reconstruction from
      September 2007 to February 2008. We assessed known patient and procedure-specific
      risks for PONV after DIEPs, prophylactic antiemetic regimens, incidence, and
      severity of PONV, postoperative antiemetic rescues, and effects of risks and
      treatments on symptoms. RESULTS: Three or more established risks existed in all
      patients, with up to seven risks per patient. Although 90% of patients received
      diverse prophylaxis, 76% of patients experienced PONV, and 66% experienced its
      severe form, emesis. Early PONV (73%) was frequent; symptoms were long lasting
      (average 20 hours for nausea and emesis); and multiple rescue medications were
      frequently required (55% for nausea, 58% for emesis). Length of surgery and
      nonsmoking statistically significantly impacted PONV. CONCLUSION: We identify
      previously undocumented high risks for PONV in DIEP patients. High frequency,
      severity, and refractoriness of PONV occur despite standard prophylaxis. Plastic
      surgeons and anesthesiologists should further investigate methods to optimize
      PONV prophylaxis and treatment in DIEP flap patients.

PMID- 24038428
TI  - An increase in voltage-gated sodium channel current elicits microglial activation
      followed inflammatory responses in vitro and in vivo after spinal cord injury.
AB  - Inflammation induced by microglial activation plays a pivotal role in progressive
      degeneration after traumatic spinal cord injury (SCI). Voltage-gated sodium
      channels (VGSCs) are also implicated in microglial activation following injury.
      However, direct evidence that VGSCs are involved in microglial activation after
      injury has not been demonstrated yet. Here, we show that the increase in VGSC
      inward current elicited microglial activation followed inflammatory responses,
      leading to cell death after injury in vitro and in vivo. Isoforms of sodium
      channel, Nav 1.1, Nav 1.2, and Nav 1.6 were expressed in primary microglia, and
      the inward current of VGSC was increased by LPS treatment, which was blocked by a
      sodium channel blocker, tetrodotoxin (TTX). TTX inhibited LPS-induced NF-kappaB
      activation, expression of TNF-alpha, IL-1beta and inducible nitric oxide
      synthase, and NO production. LPS-induced p38MAPK activation followed pro-nerve
      growth factor (proNGF) production was inhibited by TTX, whereas LPS-induced JNK
      activation was not. TTX also inhibited caspase-3 activation and cell death of
      primary cortical neurons in neuron/microglia co-cultures by inhibiting LPS
      induced microglia activation. Furthermore, TTX attenuated caspase-3 activation
      and oligodendrocyte cell death at 5 d after SCI by inhibiting microglia
      activation and p38MAPK activation followed proNGF production, which is known to
      mediate oligodendrocyte cell death. Our study thus suggests that the increase in
      inward current of VGSC appears to be an early event required for microglia
      activation after injury.

PMID- 24038429
TI  - Insecticide residues in Australian plague locusts (Chortoicetes terminifera
      Walker) after ultra-low volume aerial application of the organophosphorus
      insecticide fenitrothion.
AB  - The need for locust control throughout eastern Australia during spring 2010
      provided an opportunity to quantify residues of the organophosphorus insecticide
      fenitrothion on nymphs of the Australian plague locust, Chortoicetes terminifera
      Walker. Residues were collected across the different physiological states--live,
      dead, and debilitated (characterized by ease of capture, erratic hopping, and the
      inability to remain upright)--of locust nymphs observed following exposure to
      fenitrothion. The time course of residue depletion for 72 h after spraying was
      quantified, and residue-per-unit dose values in the present study were compared
      with previous research. Fenitrothion residue-per-unit dose values ranged from 0.2
      ug/g to 31.2 ug/g (mean +/- standard error [SE] = 6.3 +/- 1.3 ug/g) in live C.
      terminifera nymps, from 0.5 ug/g to 25.5 ug/g (7.8 +/- 1.3 ug/g) in debilitated
      nymphs, and from 2.3 ug/g to 39.8 ug/g (16.5 +/- 2.8 ug/g) in dead nymphs.
      Residues of the oxidative derivative of fenitrothion, fenitrooxon, were generally
      below the limit of quantitation for the analysis (0.02 ug/g), with 2 exceptions-
      1 live and 1 debilitated sample returned residues at the limit of quantitation.
      The results of the present study suggest that sampling of acridids for risk
      assessment should include mimicking predatory behavior and be over a longer time
      course (preferably 3-24 h postspray) than sampling of vegetation (typically 1-2 h
      postspray) and that current regulatory frameworks may underestimate the risk of
      pesticides applied for locust or grasshopper control.

PMID- 24038430
TI  - UHPLC/PDA-ESI/MS analysis of the main berry and leaf flavonol glycosides from
      different Carpathian Hippophae rhamnoides L. varieties.
AB  - INTRODUCTION: Sea buckthorn (Hippophae rhamnoides L.) is known to be rich in many
      bioactive compounds (such as vitamins, phenolics, carotenoids) important for
      human health and nutrition. Among the phenolics, berries and leaves contain a
      wide range of flavonols that are good quality and authenticity biomarkers.
      OBJECTIVE: To compare the composition of the main flavonols of Romanian sea
      buckthorn berry and leaf varieties and to identify the specific biomarkers that
      contribute to sample differentiation among varieties. MATERIAL AND METHODS: Six
      varieties of cultivated sea buckthorn (ssp. Carpatica) berries and leaves were
      analysed by UHPLC/PDA-ESI/MS. RESULTS: Berries and leaves contained mainly
      isorhamnetin (I) glycosides in different ratios. Whereas I-3-neohesperidoside, I
      3-glucoside, I-3-rhamnosylglucoside, I-3-sophoroside-7-rhamnoside and free
      isorhamnetin were predominant for berries (out of 17 compounds identified), I-3
      rhamnosylglucoside, I-3-neohesperidoside, I-3-glucoside, quercetin-3-pentoside,
      kaempferol-3-rutinoside, and quercetin-3-glucoside were predominant in leaves
      (out of 19 compounds identified). Berries contained, on average, 917 mg/100 g DW
      flavonol glycosides. Leaves had higher content of flavonol glycosides than
      berries, on average 1118 mg/100 g DW. The variation of the quantitative dataset
      analysed using principal component analysis accounted for 91% of the total
      variance in the case of berries and 73% in case of leaves, demonstrating a good
      discrimination among samples. CONCLUSION: Based on quantitative analysis, by
      principal component analysis, the flavonol derivatives can be considered as
      biomarkers to discriminate among varieties and to recognise specifically the
      berry versus leaf composition.

PMID- 24038431
TI  - Using computational strategies to predict potential drugs for nasopharyngeal
      carcinoma.
AB  - BACKGROUND: Nasopharyngeal carcinoma (NPC) is a unique cancer. Refinement of
      current therapy by discovering potential drugs may be approached by several
      computational strategies. METHODS: We collected NPC genes from published
      microarray data and the literature. The NPC disease network was constructed via a
      protein-protein interaction (PPI) network. The Connectivity Map (CMap) was used
      to predict potential chemicals, and support vector machines (SVMs) were further
      utilized to classify the effectiveness of tested drugs against NPC using their
      gene expression from CMap. RESULTS: A highly interconnected network was obtained.
      Several chemically sensitive genes were identified and 87 drugs were predicted
      with the potential for treating NPC by SVM, in which nearly half of them have
      anticancer effects according to the literature. The 2 top-ranked drugs,
      thioridazine and vorinostat, were demonstrated to be effective in inhibiting NPC
      cells. CONCLUSION: This in silico approach provides a promising strategy for
      screening potential therapeutic drugs for NPC treatment.

PMID- 24038432
TI  - Hepatitis E: current status.
AB  - Acute hepatitis E is a very common disease in developing countries, to the point
      that, according to World Health Organization estimates, one third of the world's
      population has been exposed to HEV. It also causes outbreaks in refugee camps or
      after natural disasters such as floods or earthquakes. Sporadic cases of acute
      hepatitis have been observed in practically all European countries and other
      developed geographical areas, not only in travelers from endemic countries but
      also in people with no risk factors. But, lately, new aspects of this infection
      are appearing in industrialized countries such as the possibility of the disease
      becoming chronic in transplant patients, the immunocompromised in general, and
      even in patients with previous liver disease who are immunocompetent. In this
      comprehensive review, we summarize the current knowledge on HEV infection.

PMID- 24038434
TI  - Plasmonic scissors for molecular design.
AB  - Heterogeneous catalysts play an important role in surface catalytic reactions,
      but selective bond breaking and control of reaction products in catalytic
      processes remain significant challenges. High-vacuum tip-enhanced Raman
      spectroscopy (HV-TERS) is one of the best candidates to realize surface catalytic
      reactions. Herein, HV-TERS was employed in a new method to control dissociation
      by using hot electrons, generated from plasmon decay, as plasmonic scissors. In
      this method, the N=N bond in 4,4'-dimercaptoazobenzene was selectively
      dissociated by plasmonic scissors, and the reaction products formed from the
      radical fragment (SC6H5N) were controlled by varying the pH value. Under acidic
      conditions, p-aminothiophenol was produced from the radical fragment by
      attachment of hydrogen ions, whereas under alkaline conditions, 4
      nitrobenzenethiol was obtained by attachment of oxygen ions to the substrate.

PMID- 24038437
TI  - Three-dimensional microscaffolds exhibiting spatially resolved surface chemistry.
AB  - Spatial control over the surface chemistry of 3D organic-inorganic hybrid
      microscaffolds is achieved by a two-photon-triggered cycloaddition. Following a
      coating step with photoactivatable dienes via silanization, surface irradiation
      with a femtosecond-pulsed laser in the presence of functional dienophiles enables
      a site-selective alteration of the surface chemistry. Bioconjugation with
      fluorescent protein tags is employed to reveal the 3D molecular patterns. 

PMID- 24038439
TI  - Water as an activator for palladium(II)-catalyzed olefin polymerization.
AB  - By a reasonable combination of the Wacker reaction and olefin polymerization
      processes, water proves to be an excellent activator for the palladium(II)
      catalyzed polymerization of ethylene and it provides a safe, environmental
      friendly and handy initiator for olefin polymerization. The activity of the
      olefin polymerization is comparable to reactions catalyzed by the corresponding
      alkylated cationic palladium complexes. 

PMID- 24038441
TI  - Relevance of EARLYSTIM in a tertiary movement disorders center.

PMID- 24038440
TI  - Hierarchical multiple informants models: examining food environment contributions
      to the childhood obesity epidemic.
AB  - Methods for multiple informants help to estimate the marginal effect of each
      multiple source predictor and formally compare the strength of their association
      with an outcome. We extend multiple informant methods to the case of hierarchical
      data structures to account for within cluster correlation. We apply the proposed
      method to examine the relationship between features of the food environment near
      schools and children's body mass index z-scores (BMIz). Specifically, we compare
      the associations between two different features of the food environment (fast
      food restaurants and convenience stores) with BMIz and investigate how the
      association between the number of fast food restaurants or convenience stores and
      child's BMIz varies across distance from a school. The newly developed
      methodology enhances the types of research questions that can be asked by
      investigators studying effects of environment on childhood obesity and can be
      applied to other fields.

PMID- 24038438
TI  - Activation of isocyanates and carbon dioxide by a monomeric aluminium hydrazide
      as an active Lewis pair.
AB  - The monomeric aluminium hydrazide H10 C5 N?N(AltBu2 )?Ad (4; Ad=adamantyl, NC5
      H10 =piperidinyl) was obtained in high yield by hydroalumination of the
      corresponding hydrazone derivative 1. Compound 4 has a strained AlN2 heterocycle
      formed by a donor-acceptor bond between the beta-nitrogen atom of the hydrazide
      group and the aluminium atom. Opening of this bond resulted in the formation of
      an active Lewis pair that was able to cooperatively activate carbon dioxide or
      isocyanates. Insertion of the heterocumulenes into the Al?N bond selectively
      afforded a carbamate and two urea derivatives in high yield. In the first step,
      phenyl isocyanate gave the adduct 6, which has the oxygen atom coordinated to the
      aluminium atom and its central carbon atom bound to the nitrogen atom of the
      piperidine moiety. Adduct 6 represents a reasonable intermediate state for these
      activation processes. The applicability of hydroaluminated compounds, such as 4,
      in organic synthesis was demonstrated by the reaction with an imidoyl chloride,
      which gave the corresponding amidrazone derivative 9. 

PMID- 24038435
TI  - Disruption of tumor necrosis factor receptor associated factor 5 exacerbates
      pressure overload cardiac hypertrophy and fibrosis.
AB  - The cytoplasmic signaling protein tumor necrosis factor (TNF) receptor-associated
      factor 5 (TRAF5), which was identified as a signal transducer for members of the
      TNF receptor super-family, has been implicated in several biological functions in
      T/B lymphocytes and the innate immune response against viral infection. However,
      the role of TRAF5 in cardiac hypertrophy has not been reported. In the present
      study, we investigated the effect of TRAF5 on the development of pathological
      cardiac hypertrophy induced by transthoracic aorta constriction (TAC) and further
      explored the underlying molecular mechanisms. Cardiac hypertrophy and function
      were evaluated with echocardiography, hemodynamic measurements, pathological and
      molecular analyses. For the first time, we found that TRAF5 deficiency
      substantially aggravated cardiac hypertrophy, cardiac dysfunction and fibrosis in
      response to pressure overload after 4 weeks of TAC compared to wild-type (WT)
      mice. Moreover, the mitogen-activated protein/extracellular signal-regulated
      kinase kinase (MEK)-extracellular signal-regulated kinases 1/2 (ERK1/2) signaling
      pathway was more activated in TRAF5-deficient mice than WT mice. In conclusion,
      our results suggest that as an intrinsic cardioprotective factor, TRAF5 plays a
      crucial role in the development of cardiac hypertrophy through the negative
      regulation of the MEK-ERK1/2 pathway. J. Cell. Biochem. 115: 349-358, 2014. (c)
      2013 Wiley Periodicals, Inc. 

PMID- 24038443
TI  - Photoreaction of rac-leucine in ice by circularly polarized synchrotron
      radiation: temperature-induced mechanism switching from Norrish Type II to
      deamination.
AB  - The delivery of extraterrestrial organics to primitive Earth is considered to
      have triggered the origin and subsequent evolution of life. Indeed,
      enantiomerically enriched amino acids of nonterrestrial origin have been found in
      carbonaceous meteorites, and enantioselective photodecomposition by circularly
      polarized light (CPL) in outer space has been proposed to have played some role
      in the initial enantiomeric bias. To experimentally examine this possibility and
      elucidate the photoreaction mechanisms, we have studied the photolysis of racemic
      leucine (rac-Leu) in acidic and neutral ice/water media at 21-298 K with left-
      and right-CPL in an attempt to detect enantiomerically enriched D- and L-Leu,
      respectively. Comprehensive product analyses revealed that the CPL-induced
      deracemization of Leu proceeds in both acidic and neutral ice matrices even at 21
      K, and that the main mechanism switches from Norrish-type II gamma-hydrogen
      abstraction to SN i deamination on lowering the temperature. The potential role
      of the CPL-induced photodecomposition of amino acids as a source of the
      enantiomer imbalance in meteorites is discussed. 

PMID- 24038444
TI  - Whisper-like behavior in a non-human primate.
AB  - In humans, whispering has evolved as a counteractive strategy against
      eavesdropping. Some evidence for whisper-like behavior exists in a few other
      species, but has not been reported in non-human primates. We discovered the first
      evidence of whisper-like behavior in a non-human primate, the cotton-top tamarin
      (Saguinus oedipus), in the course of investigating their use of human-directed
      mobbing calls. We exposed a family of captive cotton-top tamarins to a supervisor
      who previously elicited a strong mobbing response. Simultaneous audio-video
      recordings documented the animals' behavioral and vocal responses in the
      supervisor's presence and absence. Rather than exhibiting a mobbing response and
      producing loud human-directed mobbing calls, the tamarins exhibited other anti
      predator behaviors and produced low amplitude vocalizations that initially eluded
      our detection. A post-hoc analysis of the data was conducted to test a new
      hypothesis-the tamarins were reducing the amplitude of their vocalizations in the
      context of exposure to a potential threat. Consistent with whisper-like behavior,
      the amplitude of the tamarins' vocalizations was significantly reduced only in
      the presence of the supervisor. Due to its subtle properties, this phenomenon may
      have eluded detection in this species. Increasing evidence of whisper-like
      behavior in non-human species suggests that such low amplitude signaling may
      represent a convergence in a communication strategy amongst highly social and
      cooperative species.

PMID- 24038442
TI  - Characterization of atypical language activation patterns in focal epilepsy.
AB  - OBJECTIVE: Functional magnetic resonance imaging is sensitive to the variation in
      language network patterns. Large populations are needed to rigorously assess
      atypical patterns, which, even in neurological populations, are a minority.
      METHODS: We studied 220 patients with focal epilepsy and 118 healthy volunteers
      who performed an auditory description decision task. We compared a data-driven
      hierarchical clustering approach to the commonly used a priori laterality index
      (LI) threshold (LI < 0.20 as atypical) to classify language patterns within
      frontal and temporal regions of interest. We explored (n = 128) whether IQ varied
      with different language activation patterns. RESULTS: The rate of atypical
      language among healthy volunteers (2.5%) and patients (24.5%) agreed with
      previous studies; however, we found 6 patterns of atypical language: a
      symmetrically bilateral, 2 unilaterally crossed, and 3 right dominant patterns.
      There was high agreement between classification methods, yet the cluster analysis
      revealed novel correlations with clinical features. Beyond the established
      association of left-handedness, early seizure onset, and vascular pathology with
      atypical language, cluster analysis identified an association of handedness with
      frontal lateralization, early seizure onset with temporal lateralization, and
      left hemisphere focus with a unilateral right pattern. Intelligence quotient was
      not significantly different among patterns. INTERPRETATION: Language dominance is
      a continuum; however, our results demonstrate meaningful thresholds in
      classifying laterality. Atypical language patterns are less frequent but more
      variable than typical language patterns, posing challenges for accurate
      presurgical planning. Language dominance should be assessed on a regional rather
      than hemispheric basis, and clinical characteristics should inform evaluation of
      atypical language dominance. Reorganization of language is not uniformly
      detrimental to language functioning.

PMID- 24038436
TI  - Wingless/Wnt signaling in Drosophila: the pattern and the pathway.
AB  - Wnt signaling generates pattern in all animal embryos, from flies and worms to
      humans, and promotes the undifferentiated, proliferative state critical for stem
      cells in adult tissues. Inappropriate Wnt pathway activation is the major cause
      of colorectal cancers, a leading cause of cancer death in humans. Although this
      pathway has been studied extensively for years, large gaps remain in our
      understanding of how it switches on and off, and how its activation changes
      cellular behaviors. Much of what is known about the pathway comes from genetic
      studies in Drosophila, where a single Wnt molecule, encoded by wingless (wg),
      directs an array of cell-fate decisions similar to those made by the combined
      activities of all 19 Wnt family members in vertebrates. Although Wg specifies
      fate in many tissues, including the brain, limbs, and major organs, the fly
      embryonic epidermis has proven to be a very powerful system for dissecting
      pathway activity. It is a simple, accessible tissue, with a pattern that is
      highly sensitive to small changes in Wg pathway activity. This review discusses
      what we have learned about Wnt signaling from studying mutations that disrupt
      epidermal pattern in the fly embryo, highlights recent advances and controversies
      in the field, and sets these issues in the context of questions that remain about
      how this essential signaling pathway functions.

PMID- 24038445
TI  - Four-bond deuterium isotope effects on the chemical shifts of amide nitrogens in
      proteins.
AB  - An approach towards precision NMR measurements of four-bond deuterium isotope
      effects on the chemical shifts of backbone amide nitrogen nuclei in proteins is
      described. Three types of four-bond (15) N deuterium isotope effects are
      distinguished depending on the site of proton-to-deuterium substitution:
      (4)DeltaN(N(i-1)D), (4)DeltaN(N(i+1)D) and (4)DeltaN(Cbeta,(i-1)D). All the three
      types of isotope shifts are quantified in the (partially) deuterated protein
      ubiquitin. The (4)DeltaN(N(i+1)D) and (4)DeltaN(C(beta,i-1)D) effects are by far
      the largest in magnitude and vary between 16 and 75 ppb and -18 and 46 ppb,
      respectively. A semi-quantitative correlation between experimental
      (4)DeltaN(N(i+1)D) and (4)DeltaN(C(beta,i-1)D) values and the distances between
      nitrogen nuclei and the sites of (1)H-to-D substitution is noted. The largest
      isotope shifts in both cases correspond to the shortest inter-nuclear distances.

PMID- 24038446
TI  - Phosphorylation of Smac by Akt promotes the caspase-3 activation during etoposide
      induced apoptosis in HeLa cells.
AB  - The Akt, family of serine/threonine protein kinases functions as key regulators
      of multiple aspects of cell behavior, such as survival, proliferation, migration,
      and carcinogenesis. Notably, Akt exerts its anti-apoptotic effects through the
      phosphorylation of numerous substrates related with cell cycle, genome stability,
      and cancer development. In this report, nevertheless, we focused our view on the
      novel role of Akt which involves in a pro-apoptotic action by phosphorylating
      second mitochondria derived activator of caspases (Smac) protein during etoposide
      induced apoptotic processes. Our data reveals that Akt could bind to and
      phosphorylate Smac at serine residue 67, which enhances the ability of Smac to
      interact with the cytosolic X-chromosome linked IAP (XIAP) protein. The cellular
      interaction of wild-type Smac with XIAP was enhanced with similar activation
      kinetics of Akt activity, while this interaction was markedly attenuated in cells
      expressing the phosphorylation-defective mutant S67A-Smac during etoposide
      induced apoptosis. Moreover, we provide the evidence indicating that the
      phosphorylation of Smac at ser-67 markedly upregulates the caspase-3 activity by
      promoting the interaction of Smac with XIAP. Taken together, we propose that the
      phosphorylation of Smac by Akt might be a novel mechanism that involves in
      amplification of caspase cascade pathway during etoposide-induced apoptosis in
      HeLa cells.

PMID- 24038447
TI  - The impact of tobacco control expenditures on smoking initiation and cessation.
AB  - Between 1997 and 2007, smoking prevalence declined from 33% to 28% in
      Switzerland. Over the same period, funding for tobacco control activities
      significantly increased, resulting in the implementation of a large variety of
      national and regional interventions. In this paper, I exploit variation over time
      and across cantons of tobacco control expenditures to examine the impact of these
      policies on smoking decisions. I use retrospective smoking information from the
      Swiss Health Survey (2007) and find that tobacco control expenditures decreased
      the probability of smoking initiation among adolescents and young adults and
      increased cessation rates in the general population of smokers. I estimate that
      if funding had been kept at the 1997 level, there would have been 107,000
      additional smokers in 2007.

PMID- 24038448
TI  - Comparison of an assumption-free Bayesian approach with Optimal Sampling Schedule
      to a maximum a posteriori Approach for Personalizing Cyclophosphamide Dosing.
AB  - STUDY OBJECTIVE: Variable metabolism, dose-dependent efficacy, and a narrow
      therapeutic target of cyclophosphamide (CY) suggest that dosing based on
      individual pharmacokinetics (PK) will improve efficacy and minimize toxicity.
      Real-time individualized CY dose adjustment was previously explored using a
      maximum a posteriori (MAP) approach based on a five serum-PK sampling in patients
      with hematologic malignancy undergoing stem cell transplantation. The MAP
      approach resulted in an improved toxicity profile without sacrificing efficacy.
      However, extensive PK sampling is costly and not generally applicable in the
      clinic. We hypothesize that the assumption-free Bayesian approach (AFBA) can
      reduce sampling requirements, while improving the accuracy of results. DESIGN:
      Retrospective analysis of previously published CY PK data from 20 patients
      undergoing stem cell transplantation. In that study, Bayesian estimation based on
      the MAP approach of individual PK parameters was accomplished to predict
      individualized day-2 doses of CY. Based on these data, we used the AFBA to select
      the optimal sampling schedule and compare the projected probability of achieving
      the therapeutic end points. MEASUREMENTS AND MAIN RESULTS: By optimizing the
      sampling schedule with the AFBA, an effective individualized PK characterization
      can be obtained with only two blood draws at 4 and 16 hours after administration
      on day 1. The second-day doses selected with the AFBA were significantly
      different than the MAP approach and averaged 37% higher probability of attaining
      the therapeutic targets. CONCLUSIONS: The AFBA, based on cutting-edge statistical
      and mathematical tools, allows an accurate individualized dosing of CY, with
      simplified PK sampling. This highly accessible approach holds great promise for
      improving efficacy, reducing toxicities, and lowering treatment costs.

PMID- 24038449
TI  - The germinal matrices in the developing dentate gyrus are composed of neuronal
      progenitors at distinct differentiation stages.
AB  - BACKGROUND: Differentiation of granule cells (GCs) begins from late embryonic
      stage in the developing dentate gyrus (DG). Migration of the neurogenic stem
      cells and progenitors in the developing DG makes understanding of the DG
      morphogenesis difficult. The proliferative area in the developing DG was divided
      into the three germinal matrices (GMs). However, the stage of the progenitor
      cells in each GM along the GC differentiation process is not clear. RESULTS:
      Here, we extensively compared expression of neurogenic transcription factors
      (TFs) of which sequential expression in the neocortical development and the adult
      DG neurogenesis was reported. The GC differentiation marked by Prox1 expression
      takes place from embryonic day 16.5 in the tertiary GM. Although neurogenesis in
      each GM basically proceeds along the radial axis of the forming GC layer, cells
      expressing stem cell markers were observed intermingling with NeuroD/Prox1
      expressing differentiated cells in the tertiary GM at postnatal day 5, and
      gradually restricted in the subgranular zone as the development went on.
      CONCLUSIONS: We describe expression pattern of neurogenic TFs during DG
      development, which suggests conserved sequential expression of TFs in the GC
      lineage, and spatiotemporal relationships of GC differentiation and DG
      morphogenesis during embryonic and early postnatal periods.

PMID- 24038450
TI  - Global change and mercury cycling: challenges for implementing a global mercury
      treaty.
AB  - The Minamata Convention aims to protect human health and the environment from
      anthropogenic emissions and releases of mercury. In the present study, the
      provisions of the Minamata Convention are examined to assess their influence on
      global biogeochemical cycling of Hg. Although the convention's scope covers all
      major categories of atmospheric emissions, the degree to which it will affect
      future emissions trajectories remains unclear. A box model analysis shows that
      future global biogeochemical cycling under projected technological provisions
      would result mainly in avoided increases and that estimated differences in
      atmospheric concentrations resulting from policies would be on the order of 1% to
      2% per year. Present experience suggests that scientific knowledge is not
      currently sufficient to attribute causes to changes of this magnitude.
      Enhancements to capacity to measure the effectiveness of the Minamata Convention
      are suggested, including both measurement and modeling.

PMID- 24038451
TI  - Histological evaluation of a free medial femoral condyle flap at 21 months.
AB  - Recalcitrant nonunions typically require vascularized bone for reconstruction. In
      this report, we present a case of an index finger middle phalanx nonunion that
      was successfully treated with a free medial femoral condyle corticocancellous
      flap. Nearly 2 years after the free tissue transfer, the patient underwent
      debulking of the bone flap. This gave us the unique opportunity to examine the
      histology of the vascularized bone.

PMID- 24038452
TI  - Application of time-resolved angiography with stochastic trajectories (TWIST)
      Dixon in dynamic contrast-enhanced (DCE) breast MRI.
AB  - PURPOSE: To evaluate a magnetic resonance imaging (MRI) technique that integrates
      time-resolved angiography with stochastic trajectories (TWIST) view sharing and
      Dixon for a breast dynamic contrast-enhanced (DCE)-MRI application. MATERIALS AND
      METHODS: Simulation study: K-space data at six timepoints (1 pre-, 5
      postcontrast) were generated by performing Fourier transform on a digital
      "phantom" with 3-9 mm enhancing lesions and three types of enhancement curves
      (persistent, plateau, washout). Images were reconstructed with and without TWIST.
      Clinical study: Six TWIST-Dixon image sets (one pre-, five postcontrast) were
      acquired in 18 patients on a 3T scanner, followed by one conventional image set.
      The last TWIST-Dixon and the conventional images were scored for seven criteria:
      perceived signal-to-noise ratio (P.SNR), visualization of anatomy, fat
      suppression (FS) accuracy, FS uniformity, ghosting artifact, edge ringing
      artifact, and overall image quality (IQ). RESULTS: Simulation study: With proper
      TWIST parameters (pA >=33%, pB >=50%), the enhancement underestimation was 5% or
      less for tumor size >=5 mm. Clinical study: TWIST-Dixon images have significantly
      better scores in all criteria except for ghosting artifacts, where the difference
      was not significant. CONCLUSION: With proper parameters, TWIST-Dixon provides
      higher perceived SNR, more accurate fat suppression, and better overall image
      quality for breast DCE-MRI without sacrificing accuracy in the enhancement
      estimation.

PMID- 24038453
TI  - The G protein-coupled receptor 55 ligand l-alpha-lysophosphatidylinositol exerts
      microglia-dependent neuroprotection after excitotoxic lesion.
AB  - Searching for chemical agents and molecular targets protecting against secondary
      neuronal damage reflects one major issue in neuroscience. Cannabinoids limit
      neurodegeneration by activation of neuronal G protein-coupled cannabinoid
      receptor 1 (CB1 ) and microglial G protein-coupled cannabinoid receptor 2 (CB2 ).
      However, pharmacological experiments with CB1 /CB2 -deficient mice unraveled the
      existence of further, so-called non-CB1 /non-CB2 G protein-coupled receptor (GPR)
      subtypes. GPR55, whose function in the brain is still poorly understood,
      represents a novel target for various cannabinoids. Here, we investigated whether
      GPR55 reflects a potential beneficial target in neurodegeneration by using the
      excitotoxicity in vitro model of rat organotypic hippocampal slice cultures
      (OHSC). l-alpha-Lysophosphatidylinositol (LPI), so far representing the most
      selective agonist for GPR55, protected dentate gyrus granule cells and reduced
      the number of activated microglia after NMDA (50 uM) induced lesions. The
      relevance of GPR55 activation for LPI-mediated neuroprotection was determined by
      using Gpr55 siRNA. Microglia seems to mediate the observed neuroprotection since
      their depletion in OHSC attenuated the beneficial effects of LPI. Moreover, LPI
      alone induced microglia chemotaxis but conversely significantly attenuated ATP
      triggered microglia migration. These effects seemed to be independent from
      intracellular Ca(2+) and p38 or p44/p42 MAPK phosphorylation. In conclusion, this
      study unmasked a yet unknown role for GPR55 in neuroprotection driven by LPI
      mediated modulation of microglia function.

PMID- 24038454
TI  - Swallowing outcomes in patients with oropharyngeal cancer undergoing organ
      preservation treatment.
AB  - BACKGROUND: The purpose of this study was to assess swallowing outcomes in a
      cohort of patients with oropharyngeal squamous cell carcinoma (SCC) undergoing
      nonoperative treatment. METHODS: We conducted a retrospective study of patients
      who completed videofluoroscopic swallowing studies (VFSS) after nonoperative
      treatment of oropharyngeal SCC. All patients received intensity-modulated
      radiation therapy (IMRT) +/- chemotherapy. Swallowing abnormalities were recorded
      and the Penetration Aspiration Scale (PAS) quantified airway infiltration.
      RESULTS: Posttreatment VFSS (n = 71) occurred at an average of 4.69 months
      posttreatment. Abnormal PAS was noted in 45% of swallow studies. Swallowing
      decompensations included reduced pharyngeal constriction (75%), epiglottic tilt
      (70%), cricopharyngeal opening (42%), and hyoid excursion (42%). The only
      variable independently associated with abnormal PAS was pretreatment swallowing
      difficulty (odds ratio [OR] = 4.02; p = .009). CONCLUSION: This study
      demonstrates that patients undergoing nonsurgical treatment for oropharyngeal SCC
      are at risk for posttreatment dysphagia. This suggests a need for dysphagia
      evaluation/management and refinement of interventions to minimize dysphagia.

PMID- 24038456
TI  - Novel nanostructured rare-earth-free magnetic materials with high energy
      products.
AB  - Novel nanostructured Zr2 Co11 -based magnetic materials are fabricated in a
      single step process using cluster-deposition method. The composition, atomic
      ordering, and spin structure are precisely controlled to achieve a substantial
      magnetic remanence and coercivity, as well as the highest energy product for non
      rare-earth and Pt-free permanent-magnet alloys. 

PMID- 24038455
TI  - Phylogenetic and epidemiologic evidence of multiyear incubation in human rabies.
AB  - Eight years after emigrating from Brazil, an otherwise healthy man developed
      rabies. An exposure prior to immigration was reported. Genetic analysis revealed
      a canine rabies virus variant found only in the patient's home country, and the
      patient had not traveled internationally since immigrating to the United States.
      We describe how epidemiological, phylogenetic, and viral sequencing data provided
      confirmation that rabies encephalomyelitis may present after a long, multiyear
      incubation period, a consideration that previously has been hypothesized without
      the ability to exclude a more recent exposure. Accordingly, rabies should be
      considered in the diagnosis of any acute encephalitis, myelitis, or
      encephalomyelitis.

PMID- 24038457
TI  - Sphingosine 1-phosphate receptors negatively regulate collagen type I/III
      expression in human bone marrow-derived mesenchymal stem cell.
AB  - Collagen is the most abundant structural protein in mammals and is expressed in
      various tissues. In recent years, sphingosine 1-phosphate receptors (S1PRs) have
      been proven to play an important role in the regulation of collagen expression.
      Our previous studies reported that S1PRs are involved in TGF-beta1-induced
      collagen expression via up-regulating S1PR1/3 in mouse bone marrow-derived
      mesenchymal stem cells (BMSCs), and result in experimental mouse liver
      fibrogenesis. But it remains unclear whether this process happens in human bone
      marrow-derived mesenchymal stem cells (hMSCs). In this study, we provide
      evidences that S1PR1/3, but not S1PR2, negatively regulate the expression of
      collagen in hMSCs using cellular and molecular approaches in vitro. We find that
      treatment of hMSCs with TGF-beta1 up-regulated collagen expression in a dose- and
      time-dependent manner. Meanwhile, TGF-beta1 inhibited the expression of S1PR1/3,
      but not S1PR2, in hMSCs in a time-dependent manner. Furthermore, either selective
      knock-down of S1PR1 or silencing S1PR3 induced collagen alpha1(I) and collagen
      alpha1(III) expression in hMSCs. In contrast, inhibition of S1PR2 by siRNA had no
      effects on the expression of collagen. Altogether, all these findings
      demonstrated that collagen expression was negatively regulated by S1PR1 and S1PR3
      in hMSCs. This study highlights the differences between hMSCs and mouse BMSCs,
      provides a new regulation mechanism for collagen expression, and points out the
      risk of utilizing hMSCs in clinical applications.

PMID- 24038458
TI  - Inverse probability weighting for covariate adjustment in randomized studies.
AB  - Covariate adjustment in randomized clinical trials has the potential benefit of
      precision gain. It also has the potential pitfall of reduced objectivity as it
      opens the possibility of selecting a 'favorable' model that yields strong
      treatment benefit estimate. Although there is a large volume of statistical
      literature targeting on the first aspect, realistic solutions to enforce
      objective inference and improve precision are rare. As a typical randomized trial
      needs to accommodate many implementation issues beyond statistical
      considerations, maintaining the objectivity is at least as important as precision
      gain if not more, particularly from the perspective of the regulatory agencies.
      In this article, we propose a two-stage estimation procedure based on inverse
      probability weighting to achieve better precision without compromising
      objectivity. The procedure is designed in a way such that the covariate
      adjustment is performed before seeing the outcome, effectively reducing the
      possibility of selecting a 'favorable' model that yields a strong intervention
      effect. Both theoretical and numerical properties of the estimation procedure are
      presented. Application of the proposed method to a real data example is
      presented.

PMID- 24038459
TI  - Possible mechanism of subthalamic nucleus stimulation-induced acute renal
      failure: a virally mediated transsynaptic tracing study in transgenic mouse
      model.

PMID- 24038460
TI  - Enantioselective 1,6-conjugate addition of dialkylzinc reagents to acyclic
      dienones catalyzed by Cu-DiPPAM complex-extension to asymmetric sequential
      1,6/1,4-conjugate addition.
AB  - C?C coupling: DiPPAM 1 and BINAP 2 ligands led to divergent behaviors in the
      asymmetric conjugate addition (ACA) of dialkylzinc reagents to linear
      aryldienones, which were applied to the development of a highly selective
      sequential asymmetric 1,6/1,4-ACA process (see scheme; Tf = triflate, DBU = 1,8
      diazabicyclo[5.4.0]undec-7-ene).

PMID- 24038461
TI  - Effects of heme oxygenase-1 on bacterial antigen-induced articular chondrocyte
      catabolism in vitro.
AB  - This study tested the hypothesis that heme oxygenase-1 (HO-1) expression
      counteracts bacterial antigen-induced catabolic metabolism in human articular
      chondrocytes. HO-1 expression was induced in chondrocytes by the iron-containing
      porphoryin, hemin. Anti-catabolic and anti-apoptotic effects of HO-1 expression
      were evaluated following bacterial antigen (lipopolysaccharides, LPS) activation
      of chondrocytes by quantification of cytokine and cartilage matrix protein
      expression. Effects of HO-1 over-expression on chondrocyte matrix metabolism were
      evaluated using plasmid-driven protein synthesis. Hemin increased HO-1 expression
      and LPS increased interleukin-1beta and interleukin-6 gene and protein expression
      in chondrocytes. Hemin-induced HO-1 decreased LPS-induced interleukin-1beta and
      interleukin-6 gene and protein expression. Increased HO-1 expression partially
      reversed LPS-suppression of aggrecan and type II collagen gene expression and
      suppressed LPS-induced gene expression of IL-6, inducible nitric oxide synthase
      (iNOS), matrix metalloproteinases (MMPs), and IL-1beta. HO-1 induction was
      inversely correlated with LPS-induced chondrocyte apoptosis. HO-1 over-expression
      in chondrocytes decreased matrix protein gene expression. With LPS activation,
      increased HO-1 expression decreased chondrocyte catabolism, partially reversed
      LPS-dependent inhibition of cartilage matrix protein expression and protected
      against apoptosis. Without LPS, hemin-induced HO-1 and plasmid-based over
      expression of HO-1 inhibited cartilage matrix gene expression. The results
      suggest that elevated HO-1 expression in chondrocytes is protective of cartilage
      in inflamed joints but may otherwise suppress matrix turn over.

PMID- 24038462
TI  - Longitudinal relaxation enhancement in 1H NMR spectroscopy of tissue metabolites
      via spectrally selective excitation.
AB  - Nuclear magnetic resonance spectroscopy is governed by longitudinal (T1)
      relaxation. For protein and nucleic acid experiments in solutions, it is well
      established that apparent T1 values can be enhanced by selective excitation of
      targeted resonances. The present study explores such longitudinal relaxation
      enhancement (LRE) effects for molecules residing in biological tissues. The
      longitudinal relaxation recovery of tissue resonances positioned both down- and
      upfield of the water peak were measured by spectrally selective
      excitation/refocusing pulses, and compared with conventional water-suppressed,
      broadband-excited counterparts at 9.4 T. Marked LRE effects with up to threefold
      reductions in apparent T1 values were observed as expected for resonances in the
      6-9 ppm region; remarkably, statistically significant LRE effects were also found
      for several non-exchanging metabolite resonances in the 1-4 ppm region,
      encompassing 30-50 % decreases in apparent T1 values. These LRE effects suggest a
      novel means of increasing the sensitivity of tissue-oriented experiments, and
      open new vistas to investigate the nature of interactions among metabolites,
      water and macromolecules at a molecular level.

PMID- 24038463
TI  - Exploring supramolecular self-assembly of tetraarylporphyrins by halogen bonding:
      crystal engineering with diversely functionalized six-coordinate tin(L)2
      porphyrin tectons.
AB  - This study targets the construction of porphyrin assemblies directed by halogen
      bonds, by utilizing a series of purposely synthesized Sn(axial ligand)2
      (5,10,15,20-tetraarylporphyrin) [Sn(L)2-TArP] complexes as building units. The
      porphyrin moiety and the axial ligands in these compounds contain different
      combinations of complimentary molecular recognition functions. The former bears p
      iodophenyl, p-bromophenyl, 4'-pyridyl, or 3'-pyridyl substituents at the meso
      positions of the porphyrin ring. The latter comprises either a carboxylate or
      hydroxy anchor for attachment to the porphyrin-inserted tin ion and a pyridyl-,
      benzotriazole-, or halophenyl-type aromatic residue as the potential binding
      site. The various complexes were structurally analyzed by single-crystal X-ray
      diffraction, accompanied by computational modeling evaluations. Halogen-bonding
      interactions between the lateral aryl substituents of one unit of the porphyrin
      complex and the axial ligands of neighboring moieties was successfully expressed
      in several of the resulting samples. Their occurrence is affected by structural
      (for example, specific geometry of the six-coordinate complexes) and electronic
      effects (for example, charge densities and electrostatic potentials). The
      shortest intermolecular I???N halogen-bonding distance of 2.991 A was observed
      between iodophenyl (porphyrin) and benzotriazole (axial ligand) moieties.
      Manifestation of halogen bonds in these relatively bulky compounds without
      further activation of the halophenyl donor groups by electron-withdrawing
      substituents is particularly remarkable.

PMID- 24038464
TI  - The influence of TP53 mutations on the prognosis of patients with early stage non
      small cell lung cancer may depend on the intratumor heterogeneity of the
      mutations.
AB  - A large number of studies have evaluated the impact of TP53 mutations on the
      prognosis of patients with non-small cell lung cancer (NSCLC); however, the
      results of these studies are still controversial. Recently, considerable
      intratumor heterogeneity for genetic alterations has been demonstrated in various
      human cancers, including lung cancer. In the present study, we evaluated TP53
      mutations in NSCLCs by direct sequencing and observed remarkable variation in the
      values of relative intensity (RI, the height of the peak of mutated allele/the
      height of the peak of non-mutated allele) of the mutations. We also examined
      whether the RI values were associated with intratumor heterogeneity of TP53
      mutations. In addition, we evaluated the relationship between TP53 mutations and
      survival outcome. The patients with a TP53 mutation did not have significantly
      worse survival compared to those without the mutation. However, when tumors with
      a TP53 mutation were categorized into two groups, those with a low and those with
      a high RI, the latter group had significantly worse survival compared to those
      with wild-type TP53 (adjusted hazard ratio = 2.58, 95% confidence interval = 1.21
      5.48, P = 0.01), whereas the former group did not. These results suggest that
      intratumor genetic heterogeneity may be an important factor in determining the
      role of TP53 mutations on the prognosis of NSCLC patients.

PMID- 24038465
TI  - On the structural basis and design guidelines for type II topoisomerase-targeting
      anticancer drugs.
AB  - Type II topoisomerases (Top2s) alter DNA topology via the formation of an enzyme
      DNA adduct termed cleavage complex, which harbors a transient double-strand break
      in one DNA to allow the passage of another. Agents targeting human Top2s are
      clinically active anticancer drugs whose trapping of Top2-mediated DNA breakage
      effectively induces genome fragmentation and cell death. To understand the
      structural basis of this drug action, we previously determined the structure of
      human Top2 beta-isoform forming a cleavage complex with the drug etoposide and
      DNA, and described the insertion of drug into DNA cleavage site and drug-induced
      decoupling of catalytic groups. By developing a post-crystallization drug
      replacement procedure that simplifies structural characterization of drug
      stabilized cleavage complexes, we have extended the analysis toward other
      structurally distinct drugs, m-AMSA and mitoxantrone. Besides the expected drug
      intercalation, a switch in ribose puckering in the 3'-nucleotide of the cleavage
      site was robustly observed in the new structures, representing a new mechanism
      for trapping the Top2 cleavage complex. Analysis of drug-binding modes and the
      conformational landscapes of the drug-binding pockets provide rationalization of
      the drugs' structural-activity relationships and explain why Top2 mutants exhibit
      differential effects toward each drug. Drug design guidelines were proposed to
      facilitate the development of isoform-specific Top2-targeting anticancer agents. 

PMID- 24038466
TI  - ATR kinase activation in G1 phase facilitates the repair of ionizing radiation
      induced DNA damage.
AB  - The kinase ATR is activated by RPA-coated single-stranded DNA generated at
      aberrant replicative structures and resected double strand breaks. While many
      hundred candidate ATR substrates have been identified, the essential role of ATR
      in the replicative stress response has impeded the study of ATR kinase-dependent
      signalling. Using recently developed selective drugs, we show that ATR inhibition
      has a significantly more potent effect than ATM inhibition on ionizing radiation
      (IR)-mediated cell killing. Transient ATR inhibition for a short interval after
      IR has long-term consequences that include an accumulation of RPA foci and a
      total abrogation of Chk1 S345 phosphorylation. We show that ATR kinase activity
      in G1 phase cells is important for survival after IR and that ATR colocalizes
      with RPA in the absence of detectable RPA S4/8 phosphorylation. Our data reveal
      that, unexpectedly, ATR kinase inhibitors may be more potent cellular
      radiosensitizers than ATM kinase inhibitors, and that this is associated with a
      novel role for ATR in G1 phase cells. 

PMID- 24038468
TI  - Structural insights into Paf1 complex assembly and histone binding.
AB  - The highly conserved Paf1 complex (PAF1C) plays critical roles in RNA polymerase
      II transcription elongation and in the regulation of histone modifications. It
      has also been implicated in other diverse cellular activities, including
      posttranscriptional events, embryonic development and cell survival and
      maintenance of embryonic stem cell identity. Here, we report the structure of the
      human Paf1/Leo1 subcomplex within PAF1C. The overall structure reveals that the
      Paf1 and Leo1 subunits form a tightly associated heterodimer through antiparallel
      beta-sheet interactions. Detailed biochemical experiments indicate that Leo1
      binds to PAF1C through Paf1 and that the Ctr9 subunit is the key scaffold protein
      in assembling PAF1C. Furthermore, we show that the Paf1/Leo1 heterodimer is
      necessary for its binding to histone H3, the histone octamer, and nucleosome in
      vitro. Our results shed light on the PAF1C assembly process and substrate
      recognition during various PAF1C-coordinated histone modifications. 

PMID- 24038467
TI  - A transient alpha-helical molecular recognition element in the disordered N
      terminus of the Sgs1 helicase is critical for chromosome stability and binding of
      Top3/Rmi1.
AB  - The RecQ-like DNA helicase family is essential for the maintenance of genome
      stability in all organisms. Sgs1, a member of this family in Saccharomyces
      cerevisiae, regulates early and late steps of double-strand break repair by
      homologous recombination. Using nuclear magnetic resonance spectroscopy, we show
      that the N-terminal 125 residues of Sgs1 are disordered and contain a transient
      alpha-helix that extends from residue 25 to 38. Based on the residue-specific
      knowledge of transient secondary structure, we designed proline mutations to
      disrupt this alpha-helix and observed hypersensitivity to DNA damaging agents and
      increased frequency of genome rearrangements. In vitro binding assays show that
      the defects of the proline mutants are the result of impaired binding of Top3 and
      Rmi1 to Sgs1. Extending mutagenesis N-terminally revealed a second functionally
      critical region that spans residues 9-17. Depending on the position of the
      proline substitution in the helix functional impairment of Sgs1 function varied,
      gradually increasing from the C- to the N-terminus. The multiscale approach we
      used to interrogate structure/function relationships in the long disordered N
      terminal segment of Sgs1 allowed us to precisely define a functionally critical
      region and should be generally applicable to other disordered proteins. 

PMID- 24038469
TI  - A quality control system for profiles obtained by ChIP sequencing.
AB  - The absence of a quality control (QC) system is a major weakness for the
      comparative analysis of genome-wide profiles generated by next-generation
      sequencing (NGS). This concerns particularly genome binding/occupancy profiling
      assays like chromatin immunoprecipitation (ChIP-seq) but also related enrichment
      based studies like methylated DNA immunoprecipitation/methylated DNA binding
      domain sequencing, global run on sequencing or RNA-seq. Importantly, QC
      assessment may significantly improve multidimensional comparisons that have great
      promise for extracting information from combinatorial analyses of the global
      profiles established for chromatin modifications, the bindings of epigenetic and
      chromatin-modifying enzymes/machineries, RNA polymerases and transcription
      factors and total, nascent or ribosome-bound RNAs. Here we present an approach
      that associates global and local QC indicators to ChIP-seq data sets as well as
      to a variety of enrichment-based studies by NGS. This QC system was used to
      certify >5600 publicly available data sets, hosted in a database for data mining
      and comparative QC analyses. 

PMID- 24038470
TI  - DNA polymerase delta stalls on telomeric lagging strand templates independently
      from G-quadruplex formation.
AB  - Previous evidence indicates that telomeres resemble common fragile sites and
      present a challenge for DNA replication. The precise impediments to replication
      fork progression at telomeric TTAGGG repeats are unknown, but are proposed to
      include G-quadruplexes (G4) on the G-rich strand. Here we examined DNA synthesis
      and progression by the replicative DNA polymerase delta/proliferating cell
      nuclear antigen/replication factor C complex on telomeric templates that mimic
      the leading C-rich and lagging G-rich strands. Increased polymerase stalling
      occurred on the G-rich template, compared with the C-rich and nontelomeric
      templates. Suppression of G4 formation by substituting Li(+) for K(+) as the
      cation, or by using templates with 7-deaza-G residues, did not alleviate Pol
      delta pause sites within the G residues. Furthermore, we provide evidence that G4
      folding is less stable on single-stranded circular TTAGGG templates where ends
      are constrained, compared with linear oligonucleotides. Artificially stabilizing
      G4 structures on the circular templates with the G4 ligand BRACO-19 inhibited Pol
      delta progression into the G-rich repeats. Similar results were obtained for
      yeast and human Pol delta complexes. Our data indicate that G4 formation is not
      required for polymerase stalling on telomeric lagging strands and suggest that an
      alternative mechanism, in addition to stable G4s, contributes to replication
      stalling at telomeres. 

PMID- 24038471
TI  - Self-duplexing CUG repeats selectively inhibit mutant huntingtin expression.
AB  - Huntington's disease (HD) is a neurodegenerative genetic disorder caused by the
      expansion of the CAG repeat in the translated sequence of the HTT gene. This
      expansion generates a mutant huntingtin protein that contains an abnormally
      elongated polyglutamine tract, which, together with mutant transcript, causes
      cellular dysfunction. Currently, there is no curative treatment available to
      patients suffering from HD; however, the selective inhibition of the mutant
      allele expression is a promising therapeutic option. In this study, we developed
      a new class of CAG repeat-targeting silencing reagents that consist of self
      duplexing CUG repeats. Self-duplex formation was induced through one or several U
      base substitutions. A number of self-duplexing guide-strand-only short
      interfering RNAs have been tested through transfection into cells derived from HD
      patients, showing distinct activity profiles. The best reagents were highly
      discriminatory between the normal and mutant HTT alleles (allele selectivity) and
      the HTT transcript and other transcripts containing shorter CAG repeats (gene
      selectivity). We also demonstrated that the self-duplexing CUG repeat short
      interfering RNAs use the RNA interference pathway to elicit silencing, and repeat
      targeting reagents showed similar activity and selectivity when expressed from
      short hairpin RNA vectors to achieve more durable silencing effects. 

PMID- 24038473
TI  - The dire need for cancer health disparities research.

PMID- 24038485
TI  - Beyond bureaucracy: emerging trends in social care informatics.
AB  - Existing information technology systems in much of UK social care have been
      designed to serve the interests of the bureaucracy rather than supporting
      professional practice or improving services to the public. The ill-starred
      Integrated Children's System in statutory children's services is typical. The
      Integrated Children's System is a system for form-filling, micro-managing
      professional practice through an enforced regime of standard processes and time
      scales. In this article, we argue against this dominant design. We provide
      several examples where technology has enabled alternative modes of support for
      professional work, based on socio-technical principles. One such system is
      Patchwork, which describes itself as a 'Facebook for Social Work'; its aim is to
      support multi-professional teams working with vulnerable families. 

PMID- 24038472
TI  - Long non-coding RNA identification over mouse brain development by integrative
      modeling of chromatin and genomic features.
AB  - In silico prediction of genomic long non-coding RNAs (lncRNAs) is prerequisite to
      the construction and elucidation of non-coding regulatory network. Chromatin
      modifications marked by chromatin regulators are important epigenetic features,
      which can be captured by prevailing high-throughput approaches such as ChIP
      sequencing. We demonstrate that the accuracy of lncRNA predictions can be greatly
      improved when incorporating high-throughput chromatin modifications over mouse
      embryonic stem differentiation toward adult Cerebellum by logistic regression
      with LASSO regularization. The discriminating features include H3K9me3, H3K27ac,
      H3K4me1, open reading frames and several repeat elements. Importantly, chromatin
      information is suggested to be complementary to genomic sequence information,
      highlighting the importance of an integrated model. Applying integrated model, we
      obtain a list of putative lncRNAs based on uncharacterized fragments from
      transcriptome assembly. We demonstrate that the putative lncRNAs have regulatory
      roles in vicinity of known gene loci by expression and Gene Ontology enrichment
      analysis. We also show that the lncRNA expression specificity can be efficiently
      modeled by the chromatin data with same developmental stage. The study not only
      supports the biological hypothesis that chromatin can regulate expression of
      tissue-specific or developmental stage-specific lncRNAs but also reveals the
      discriminating features between lncRNA and coding genes, which would guide
      further lncRNA identifications and characterizations. 

PMID- 24038486
TI  - Ecogenetics of mercury: from genetic polymorphisms and epigenetics to risk
      assessment and decision-making.
AB  - The risk assessment of mercury (Hg), in both humans and wildlife, is made
      challenging by great variability in exposure and health effects. Although disease
      risk arises following complex interactions between genetic ("nature") and
      environmental ("nurture") factors, most Hg studies thus far have focused solely
      on environmental factors. In recent years, ecogenetic-based studies have emerged
      and have started to document genetic and epigenetic factors that may indeed
      influence the toxicokinetics or toxicodynamics of Hg. The present study reviews
      these studies and discusses their utility in terms of Hg risk assessment,
      management, and policy and offers perspectives on fruitful areas for future
      research. In brief, epidemiological studies on populations exposed to inorganic
      Hg (e.g., dentists and miners) or methylmercury (e.g., fish consumers) are
      showing that polymorphisms in a number of environmentally responsive genes can
      explain variations in Hg biomarker values and health outcomes. Studies on mammals
      (wildlife, humans, rodents) are showing Hg exposures to be related to epigenetic
      marks such as DNA methylation. Such findings are beginning to increase
      understanding of the mechanisms of action of Hg, and in doing so they may help
      identify candidate biomarkers and pinpoint susceptible groups or life stages.
      Furthermore, they may help refine uncertainty factors and thus lead to more
      accurate risk assessments and improved decision-making.

PMID- 24038487
TI  - Influence of the pedicle orientation and length on viability of unipedicled
      venous island flaps.
AB  - The use of unipedicled venous flaps has been limited due to their unconventional
      perfusion patterns and inconsistent survival. Further information regarding the
      optimal conditions required for unipedicled venous flap coverage is needed to
      increase flap survival. The purpose of this study was to investigate the effect
      of the pedicle orientation and length on the viability of unipedicled venous
      flaps based on a review of our clinical experience. Thirty-one skin and soft
      tissue hand defects of 29 patients were treated with unipedicled venous flaps.
      Sixteen defects were treated with proximally pedicled flaps and 15 were treated
      with distally pedicled flaps. Five of the 16 proximally pedicled flaps and eight
      of the 15 distally pedicled flaps had pedicle lengths >= 5 cm. All proximally
      pedicled flaps survived, and distally pedicled flaps with pedicle lengths <5 cm
      (n = 7) also survived. Distally pedicled flaps with pedicle lengths >=5 cm (n =
      8) developed congestion within 1-2 days after surgery, and external bleeding was
      applied. Four of the eight flaps survived completely, and partial necrosis
      developed in the other four. The results demonstrate that proximally pedicled
      venous flaps of the hand can survive regardless of pedicle length. Distally
      pedicled venous flaps can also survive completely when pedicle length is <5 cm.
      Distally pedicled venous flaps with pedicle lengths >=5 cm should be used with
      caution.

PMID- 24038488
TI  - Mechanisms of muscle growth and atrophy in mammals and Drosophila.
AB  - BACKGROUND: The loss of skeletal muscle mass (atrophy) that accompanies disuse
      and systemic diseases is highly debilitating. Although the pathogenesis of this
      condition has been primarily studied in mammals, Drosophila is emerging as an
      attractive system to investigate some of the mechanisms involved in muscle growth
      and atrophy. RESULTS: In this review, we highlight the outstanding unsolved
      questions that may benefit from a combination of studies in both flies and
      mammals. In particular, we discuss how different environmental stimuli and
      signaling pathways influence muscle mass and strength and how a variety of
      disease states can cause muscle wasting. CONCLUSIONS: Studies in Drosophila and
      mammals should help identify molecular targets for the treatment of muscle
      wasting in humans.

PMID- 24038490
TI  - A prospective newborn screening and treatment program for sickle cell anemia in
      Luanda, Angola.
AB  - Over 300,000 infants are born annually with sickle cell anemia (SCA) in sub
      Saharan Africa, and >50% die young from infection or anemia, usually without
      diagnosis of SCA. Early identification by newborn screening (NBS), followed by
      simple interventions dramatically reduced the mortality of SCA in the United
      States, but this strategy is not yet established in Africa. We designed and
      implemented a proof-of-principle NBS and treatment program for SCA in Angola,
      with focus on capacity building and local ownership. Dried bloodspots from
      newborns were collected from five birthing centers. Hemoglobin identification was
      performed using isoelectric focusing; samples with abnormal hemoglobin patterns
      were analyzed by capillary electrophoresis. Infants with abnormal FS or FSC
      patterns were enrolled in a newborn clinic to initiate penicillin prophylaxis and
      receive education, pneumococcal immunization, and insecticide-treated bed nets. A
      total of 36,453 infants were screened with 77.31% FA, 21.03% FAS, 1.51% FS, and
      0.019% FSC. A majority (54.3%) of affected infants were successfully contacted
      and brought to clinical care. Compliance in the newborn clinic was excellent
      (96.6%). Calculated first-year mortality rate for babies with SCA compares
      favorably to the national infant mortality rate (6.8 vs. 9.8%). The SCA burden is
      extremely high in Angola, but NBS is feasible. Capacity building and training
      provide local healthcare workers with skills needed for a functional screening
      program and clinic. Contact and retrieval of all affected SCA infants remains a
      challenge, but families are compliant with clinic appointments and treatment.
      Early mortality data suggest screening and early preventive care saves lives.

PMID- 24038489
TI  - In vivo alterations in drug metabolism and transport pathways in patients with
      chronic kidney diseases.
AB  - STUDY OBJECTIVE: This study was designed to prospectively evaluate the in vivo
      activities of drug transporters, metabolizing enzymes, and pharmacokinetics in
      patients with chronic kidney diseases (CKD) caused by glomerulonephritis and
      nonglomerular etiologies. DESIGN: A prospective study design. PARTICIPANTS:
      Eighteen adults with CKD. SETTING: General Clinical Research Center at the
      University of North Carolina and University of Pittsburgh. MEASUREMENT AND MAIN
      RESULTS: Blood and urine were collected and assayed for fexofenadine (transporter
      function) as well as flurbiprofen and 4-hydroxyflurbiprofen (CYP2C9 function).
      CYP3A4 activity was assessed by the erythromycin breath test. In patients with
      glomerulonephritis, the apparent oral clearance of fexofenadine (representing
      transporter activity) was 58.8 +/- 34.4 L/hour, documenting a 40% reduction
      compared with previous data in healthy controls. The CYP2C9 pathway (4
      hydroxyflurbiprofen formation clearance) was similar in all the patients with CKD
      and was concordant with previous reports of patients with end-stage renal disease
      (ESRD) and healthy controls. For flurbiprofen, patients with glomerulonephritis
      had higher oral clearance than those with nonglomerular CKD, suggesting higher
      unbound fraction and enhanced metabolism through other (non-CYP2C9) routes. No
      statistically significant differences in CYP3A4 activity were observed in either
      group of patients or when compared with results from previous studies of patients
      with ESRD or healthy controls. CONCLUSIONS: The current study suggests no
      statistically significant differences in the in vivo activity of CYP2C9 and
      CYP3A4 in patients with either glomerulonephritis or nonglomerular CKD. However,
      there are clinical differences in transporter function as defined by at least a
      25% reduction in activity in glomerulonephritis as opposed to healthy controls. A
      similarity in the in vivo function between patients with glomerulonephritis and
      ESRD, and between patients with glomerulonephritis and nonglomerular CKD was
      present despite significant differences in kidney function. Further in vivo and
      in vitro studies are necessary to fully understand the physiologic and disease
      specific nuances that contribute to alterations in drug disposition in patients
      with kidney diseases.

PMID- 24038492
TI  - Promotion of malaria home-based treatment in Africa: The dangers of creating a
      second health system.
AB  - Many African countries have begun to scale-up home-based management of malaria
      (HMM) with artemisinin-based combination therapy. Evidence shows that this
      strategy gives efficient results in reducing the malaria burden. This initiative
      should be promoted to reduce malaria-related mortality and morbidity. HMM could,
      however, lead to critical public health problems, including the misdiagnosis of
      serious infections distinct from malaria as well as desertion of the public
      health system. I wish to emphasise the importance of improving the existing
      health system in African malaria-endemic areas for long-term improvement of
      population health in this context of HMM implementation. 

PMID- 24038491
TI  - T(2) relaxation time measurements are limited in monitoring progression, once
      advanced cartilage defects at the knee occur: longitudinal data from the
      osteoarthritis initiative.
AB  - PURPOSE: To study the natural evolution of cartilage T2 relaxation times in knees
      with various extents of morphological cartilage abnormalities, assessed with 3
      Tesla MRI from the Osteoarthritis Initiative. MATERIALS AND METHODS: Right knee
      MRIs of 245, 45- to 60-year-old individuals without radiographic osteoarthritis
      (OA) were included. Cartilage was segmented and T2 maps were generated in five
      compartments (patella, medial and lateral femoral condyle, medial, and lateral
      tibia) at baseline and 2-year follow-up. We examined the association of T2 values
      and 2-year change of T2 values with various Whole-Organ MR Imaging Scores
      (WORMS). Statistical analysis was performed with analysis of variance and
      Students t-tests. RESULTS: Higher baseline T2 was associated with more severe
      cartilage defects at baseline and subsequent cartilage loss (P < 0.001). However,
      longitudinal T2 change was inversely associated with both baseline (P = 0.038)
      and follow-up (P = 0.002) severity of cartilage defects. Knees that developed new
      cartilage defects had smaller increases in T2 than subjects without defects (P =
      0.045). Individuals with higher baseline T2 showed smaller T2 increases over time
      (P < 0.001). CONCLUSION: An inverse correlation of longitudinal T2 changes versus
      baseline T2 values and morphological cartilage abnormalities suggests that once
      morphological cartilage defects occur, T2 values may be limited for evaluating
      further cartilage degradation.

PMID- 24038493
TI  - Ensuring tuberculosis infection control to support greater involvement of people
      living with HIV in health care.
AB  - Health care workers (HCWs) in high TB burden countries bear significant risks of
      being infected with Mycobacterium tuberculosis and developing TB disease through
      their work. In recent years, an increasing number of people living with HIV
      (PLHIV) are taking part in delivering HIV and other health services in resource
      limited settings with high TB burden. The greater involvement of PLHIV in health
      service delivery has many beneficial consequences on individuals and health
      systems, however, the involvement creates considerable opportunities for them to
      be exposed to patients with infectious TB disease. Due to their immunodeficiency,
      PLHIV are far more likely to develop active TB following the infection. Available
      evidence and recently revised WHO policy guidance on TB infection control suggest
      simple, predominantly administrative control measures are feasible and effective
      in reducing the infection. Nevertheless, many countries are still at the early
      stage of developing infection control policies. We call for evidence-based
      infection control measures in order to ensure a safe working environment for
      PLHIV in support of their greater involvement in health care. More research is
      needed to strengthen knowledge on TB infection risks amongst PLHIV through
      involvement in service delivery, and optimal interventions to reduce it. 

PMID- 24038494
TI  - Outbreak response immunisation: The experience of Chad during recurrent measles
      epidemics in 2005 and 2010.
AB  - Despite impressive gains in measles control globally, measles epidemics continue
      to occur in countries with insufficient vaccination coverage. WHO guidelines now
      recommend outbreak response immunisation (ORI) for controlling measles outbreaks
      in certain contexts. The objective of this study was to describe late and early
      response vaccination activities during two consecutive measles outbreaks that
      occurred in 2005 and 2010 in N'Djamena, Chad. Using Lot Quality Assurance
      Sampling, vaccination coverage was estimated to be low before the interventions.
      Following mass vaccination campaigns, measles cases declined. The timeliness and
      quality of ORI activities are crucial determinants of success. However, effective
      outbreak response should be accompanied by strong routine vaccination programmes
      to ensure sustainable high vaccination coverage. 

PMID- 24038495
TI  - Rabies control initiative in Tamil Nadu, India: A test case for the 'One Health'
      approach.
AB  - Although India accounts for nearly 50% of the global rabies mortality, there is
      no organised national rabies control programme. Rabies control is generally
      confined to small urban pockets, with minimal intersectoral co-ordination. Tamil
      Nadu is the first state in India to implement a state-wide, multisectoral rabies
      control initiative. The CDC Program Evaluation Framework guided the current
      assessment of this rabies prevention and control initiative in Tamil Nadu.
      Principle stakeholders were engaged through a series of interviews in order to
      document policy initiatives, to describe the programme and to understand their
      various roles. Surveillance data on dog bites were triangulated with vaccine
      consumption and dog population data to identify trends at the district level in
      the state. Findings and recommendations were shared at different levels. Rabies
      control activities in Tamil Nadu were conducted by separate departments linked by
      similar objectives. In addition to public health surveillance, animal census and
      implementation of dog licensing rules, other targeted interventions included
      waste management, animal birth control and anti-rabies vaccination, awareness
      campaigns, and widespread availability of anti-rabies vaccine at all public
      health facilities. In conclusion, this assessment suggests that it is possible to
      implement a successful 'One Health' programme in an environment of strong
      political will, evidence-based policy innovations, clearly defined roles and
      responsibilities of agencies, co-ordination mechanisms at all levels, and a
      culture of open information exchange. 

PMID- 24038496
TI  - Integration of deworming into an existing immunisation and vitamin A
      supplementation campaign is a highly effective approach to maximise health
      benefits with minimal cost in Lao PDR.
AB  - Infection with soil-transmitted helminths (STH) is a major public health problem
      in many developing countries, with pregnant women and children particularly at
      risk. Preventive chemotherapy, which is the intervention currently recommended by
      the WHO against the main helminth infections including those caused by STHs, aims
      at reducing morbidity through periodical administration of anthelminthic drugs
      either alone or in combination. The Expanded Programme on Immunization is one of
      the most widely implemented health programmes in the world and has well
      established access to children and women. The present study investigated the cost
      of the provision of anthelminthic drugs during existing immunisation campaigns.
      In Lao PDR, use of this integrated approach compared with implementation of the
      vertical deworming campaign alone allowed a reduction of the individual cost of
      deworming by 10 times (from US$0.23 in the vertical deworming campaign to US$0.03
      in the integrated campaign). When drug cost was excluded, the cost of deworming
      an individual was US$0.007, implying that deworming 100 children would cost less
      than US$1 if drug donation was in place. The burden posed on health workers by
      the integration process was perceived as minimal and manageable. Moreover,
      delivery of anthelminthic drugs during immunisation campaigns enabled campaign
      teams to observe drug intake directly, which assured safety. These findings prove
      that integration is an opportunity to maximise health benefits through the
      delivery of multiple health products and the attainment of high coverage. 

PMID- 24038497
TI  - Why we need to rethink the strategy and time frame for achieving health-related
      Millennium Development Goals.
AB  - Targets and interventions for the Millennium Development Goals (MDG) related to
      reducing hunger (MDG 1) and child mortality (MDG 4) have ignored the role of
      intergenerational influences on health. In this study, the comparative importance
      of intergenerational and contemporaneous factors for achieving MDGs 1 and 4
      targets was evaluated. A database of 735 970 children from 109 Demographic and
      Health Surveys conducted between 1991 and 2008 in 54 countries was compiled.
      Modified Poisson regression models were used to estimate the association between
      child mortality/undernutrition and maternal education, wealth and height.
      Stochastic simulations of regression results were then used to evaluate changes
      in maternal height, education and wealth required to halve stunting and
      underweight and to reduce mortality by two-thirds. At mean height, 25 years of
      education were needed to achieve a two-thirds reduction in mortality, and halving
      the prevalence of stunting and underweight required 23 years and 17 years of
      education, respectively, for the poorest wealth quintile. When height was
      increased from the mean by 25 cm, the prevalence of both growth outcomes was
      halved, even for those with no education and in the poorest wealth quintile.
      These results indicate that contemporaneous interventions will achieve MDG
      targets more readily in populations with greater accumulated health stock. 

PMID- 24038498
TI  - Evaluation of household latrine coverage in Kewot woreda, Ethiopia, 3 years after
      implementing interventions to control blinding trachoma.
AB  - The SAFE strategy for trachoma control includes Surgery, Antibiotic distribution,
      Facial cleanliness and Environmental improvements, including promotion of latrine
      construction. In this study, household latrine coverage was estimated in order to
      evaluate SAFE implementation in a district of Ethiopia where reported coverage in
      rural areas was 97%. Characteristics of latrine adopters and non-adopters were
      explored. Interviews were conducted in 442 households selected at random in a
      multistage cluster sample. Overall, estimated household latrine coverage was
      56.2% (95% CI 37.5-74.8%) and in rural areas coverage was 67.7% (95% CI 59.6
      75.7%). Previously owning a latrine was reported by 12.7% (95% CI 8.9-16.5%) of
      respondents, of which 32.0% (95% CI 15.9-48.2%) had built a replacement. Latrine
      adopters were more likely to be male (P < 0.0001), to report their primary
      occupation as agriculture (P < 0.0001), have more than five residents in their
      household (P = 0.004) and live in a rural area (P < 0.0001). Respondents who were
      advised by a health extension worker (P < 0.0001) or development agent (P <
      0.0001) were more likely to have built a latrine. Household latrine coverage has
      increased from the 2007 zonal estimate (8.9%), but was lower than that reported.
      Latrine promotion should include emphasis on rebuilding latrines. More support
      may be needed by small households as well as those with a female head if
      universal latrine access is to be achieved in Kewot. 

PMID- 24038499
TI  - Cost effectiveness of child pneumococcal conjugate vaccination in GAVI-eligible
      countries.
AB  - Policy-makers increasingly rely on cost-effectiveness analysis, in addition to
      clinical effectiveness, when considering the introduction of new childhood
      vaccines. A previous analysis determined vaccination of infants with 7-valent
      pneumococcal conjugate vaccine (PCV) to be highly cost effective in preventing
      child mortality in countries eligible for financial support from the Global
      Alliance for Vaccines and Immunization (GAVI). We aimed to update this analysis
      by incorporating recent data on global disease burden, indirect effects and
      higher valency vaccines. Decision analytic models were built using an incidence
      based approach in order to evaluate a three-dose vaccination schedule of infants
      in 72 GAVI-eligible countries over a 10-year programme. Seven-, 10- and 13-valent
      vaccine formulations were each compared with no vaccination. Depending on the
      formulation used, PCV could avert 294 000-603 000 deaths and 9.3-17.6 million
      disability-adjusted life-years (DALY) annually. The majority (91%) of the DALYs
      averted would be through the vaccine's direct effects in children under-5. Using
      WHO thresholds and a negotiated average dose cost, PCV would be highly cost
      effective in 69 of 72 GAVI-eligible countries. This finding was robust when
      assumptions regarding disease epidemiology and vaccine-related effects were
      varied in sensitivity analyses. The current analysis supports PCV introduction in
      GAVI-eligible countries owing to its potential to avert substantial numbers of
      deaths at relatively low incremental costs. 

PMID- 24038500
TI  - Cost effectiveness of child pneumococcal conjugate vaccination in middle-income
      countries.
AB  - Policy-makers require information on the potential benefits of and economic case
      for pneumococcal conjugate vaccination in middle-income countries. We built
      decision analysis models to evaluate a three-dose infant series of the 7-, 10- or
      13-valent pneumococcal conjugate vaccines in 77 middle-income countries compared
      with no vaccination, accounting for direct protection of vaccinated children as
      well as herd protection and serotype replacement in unvaccinated children and
      adults. Over 10 years, pneumococcal vaccination would prevent at least 11.0
      million cases and 314 000 deaths in children under-5, one-third of the pneumonia
      and invasive disease cases and deaths that would occur in this age group without
      vaccination. Herd protection would prevent 3.1 million cases and 163 000 deaths
      in older children and adults. A total of 11.1 million discounted disability
      adjusted life-years (DALY) would be averted. At a dose cost of $10 for lower-
      middle-income and $20 for upper-middle-income countries, the net pooled (for all
      countries together) discounted vaccination cost would be $18.1 billion ($1600 per
      DALY averted). Vaccination would be cost effective for 72 countries with the 7
      valent vaccine and for all countries with the 10- or 13-valent vaccines. The
      economic case for vaccination is compelling for middle-income countries. 

PMID- 24038501
TI  - Bolivian migrants with Chagas disease in Barcelona, Spain: a qualitative study of
      dietary changes and digestive problems.
AB  - Due to international migration, Chagas disease, endemic in Latin America, has
      become more common in non-endemic areas. Chronic Chagas disease can cause damage
      to the digestive system leading to constipation. However, a range of factors
      influences constipation and a better understanding of the role of non-Chagas
      related factors is required to improve management of Chagas-related digestive
      problems. This study explores perceptions of constipation and changes in food and
      exercise habits amongst Bolivians in Barcelona, Spain. Bolivian migrants
      attending the Tropical Medicine Unit (Hospital Clinic, Barcelona) were
      interviewed about their food habits in Spain and Bolivia, migratory experience,
      work and leisure activities. Chagas seropositive participants also received
      radiological examinations. Bolivian migrants experienced dietary changes,
      influenced by work-related factors, which included reductions in quantities of
      food and liquid consumed. Almost half the participants reported changes in
      digestive rhythm since arriving in Spain. Constipation, which was common, in some
      cases was only recounted during interviews. Bolivian migrants' constipation may
      be associated with chronic Chagas disease or migration-related dietary changes.
      Careful questioning using the Rome III criteria is however required to ensure its
      diagnosis. Radiological studies are also required to confirm the role of Chagas
      disease and identify potentially serious intestinal damage. 

PMID- 24038503
TI  - Solid-state high-throughput screening for color tuning of electrochromic
      polymers.
AB  - Diffusion of two monomers and their oxidative copolymerization inside a solid
      state gel electrolyte is utilized as a method to match the monomer feed ratio to
      a color resulting from a conjugated copolymer having a single absorption in the
      visible region. Here, a combination of two monomers is used to generate a solid
      state electrochromic device of any color, except black and green, in the colored
      state with all other colors going to transmissive sky blue in the bleached state.

PMID- 24038502
TI  - Volumetric correlates of cognitive functioning in nondemented patients with
      Parkinson's disease.
AB  - A challenge in Parkinson's disease (PD) is to identify biomarkers of early
      cognitive change because functioning in some domains may be more prognostic of
      dementia. Few studies have investigated whether structural magnetic resonance
      imaging (MRI) correlates in a regionally specific manner with functioning in
      different cognitive domains. The aim of this study was to identify
      neuroanatomical correlates of executive functioning, memory, and visual cognition
      in PD without dementia. 3T MRI was conducted in 51 PD patients and 39 control
      participants. Brain volumes were measured in structures comprising the
      frontostriatal cognitive-control system, the medial temporal memory system, the
      ventral object-based system, and the dorsal spatial-based system. Measures of
      executive functioning (Stroop Test; Letter Fluency), memory (California Verbal
      Learning Test), visuospatial cognition (Judgment of Line Orientation), and
      visuoconstruction (Pentagon Copy) were correlated with volumes comprising each
      system. Poorer executive functioning largely correlated with decreased
      frontostriatal volumes. Poorer memory correlated with decreased volumes in all
      medial temporal regions, but also with frontostriatal volumes. Poorer
      visuospatial cognition correlated with decreased volumes in the object-based
      system, whereas poorer visuoconstruction correlated with decreased frontal and
      object-based system volumes. These relationships were nonsignificant in the
      control group. This is the first study to demonstrate that subtle changes in
      multiple cognitive domains in PD without dementia correlate with regional volumes
      in specific systems implicated in the development of cognitive impairment. The
      findings suggest that structural MRI holds promise as a marker of early changes
      in different brain systems, some of which may predict future cognitive
      deterioration.

PMID- 24038504
TI  - Uncoupling of neuroinflammation from axonal degeneration in mice lacking the
      myelin protein tetraspanin-2.
AB  - Deficiency of the major constituent of central nervous system (CNS) myelin,
      proteolipid protein (PLP), causes axonal pathology in spastic paraplegia type-2
      patients and in Plp1(null) -mice but is compatible with almost normal
      myelination. These observations led us to speculate that PLP's role in
      myelination may be partly compensated for by other tetraspan proteins. Here, we
      demonstrate that the abundance of the structurally related tetraspanin-2 (TSPAN2)
      is highly increased in CNS myelin of Plp1(null) -mice. Unexpectedly, Tspan2(null)
      -mutant mice generated by homologous recombination in embryonic stem cells
      displayed low-grade activation of astrocytes and microglia in white matter tracts
      while they were fully myelinated and showed no signs of axonal degeneration. To
      determine overlapping functions of TSPAN2 and PLP, Tspan2(null) *Plp1(null)
      double-mutant mice were generated. Strikingly, the activation of astrocytes and
      microglia was strongly enhanced in Tspan2(null) *Plp1(null) double-mutants
      compared with either single-mutant, but the levels of dysmyelination and axonal
      degeneration were not increased. In this model, glial activation is thus unlikely
      to be caused by axonal pathology, and vice versa does not potentiate axonal
      degeneration. Our results support the concept that multiple myelin proteins have
      distinct roles in the long-term preservation of a healthy CNS, rather than in
      myelination per se.

PMID- 24038505
TI  - Charge-recombination fluorescence from push-pull electronic systems constructed
      around amino-substituted styryl-BODIPY dyes.
AB  - A small series of donor-acceptor molecular dyads has been synthesized and fully
      characterized. In each case, the acceptor is a dicyanovinyl unit and the donor is
      a boron dipyrromethene (BODIPY) dye equipped with a single styryl arm bearing a
      terminal amino group. In the absence of the acceptor, the BODIPY-based dyes are
      strongly fluorescent in the far-red region and the relaxed excited-singlet states
      possess significant charge-transfer character. As such, the emission maxima
      depend on both the solvent polarity and temperature. With the corresponding push
      pull molecules, there is a low-energy charge-transfer state that can be observed
      by both absorption and emission spectroscopy. Here, charge-recombination
      fluorescence is weak and decays over a few hundred picoseconds or so to recover
      the ground state. Overall, these results permit evaluation of the factors
      affecting the probability of charge-recombination fluorescence in push-pull dyes.
      The photophysical studies are supported by cyclic voltammetry and DFT
      calculations. 

PMID- 24038506
TI  - Salivary duct carcinoma with rhabdoid features: report of 2 cases with
      immunohistochemical and ultrastructural analyses.
AB  - BACKGROUND: Salivary duct carcinoma with rhabdoid features is extremely rare.
      METHODS: We report 2 cases of salivary duct carcinoma with rhabdoid features
      treated at our institution. RESULTS: Case 1 was a 44-year-old Japanese man who
      had swelling in the left parotid region. This tumor consisted of residual
      pleomorphic adenoma and widely invasive carcinoma, which showed a diffuse growth
      pattern by atypical rhabdoid cells. Case 2 was a 66-year-old Japanese man who had
      swelling of the right cervical region. This submandibular tumor was also composed
      of both residual pleomorphic adenoma region and invasive adenocarcinoma
      components, whereas some metastatic lesions were purely composed of rhabdoid
      cells. Such cells were strongly and diffusely positive for cytokeratins (CKs),
      gross cystic disease fluid protein-15 (GCDFP), and androgen receptor (AR). Case 1
      was also positive for Her-2 and p53. CONCLUSION: Both patients were diagnosed
      with carcinoma ex pleomorphic adenoma and their carcinomatous components were
      composed of salivary duct carcinoma with rhabdoid features, which is a highly
      aggressive tumor, similar to salivary duct carcinoma.

PMID- 24038507
TI  - Synthesis of some new benzisothiazolone and benzenesulfonamide derivatives of
      biological interest starting from saccharin sodium.
AB  - Two new series of benzenesulfonamide (4a-f, 5a-b, 6, 7) and 1,2-benzisothiazol
      3(2H)-one-1,1-dioxide (9a-c, 10, 12a-d) derivatives were prepared starting from
      saccharin sodium. The novel compounds were characterized using elemental analyses
      and different spectroscopic methods. Assessment of the antiviral activities of
      these novel compounds against a broad panel of viruses in different cell cultures
      revealed that only the thiazole derivatives belonging to the benzisothiazol-3(2H)
      one-1,1-dioxide series are the active ones. All thiazole derivatives 12a-d showed
      activity against both varicella-zoster virus, especially TK(-) VZV strain 07-1,
      and the cytomegalovirus strains AD-169 and Davis in human embryonic lung (HEL)
      cell culture. 

PMID- 24038508
TI  - The gender-neutral timed obstacle course: a valid test of police fitness?
AB  - BACKGROUND: In the light of the Winsor review, UK police forces have been urged
      to use fitness tests as large-scale cost-effective measures of officers' fitness
      to work. One test is the Gender-Neutral Timed Obstacle Course (GeNTOC), which
      must be completed within 3min 45 s, regardless of sex. AIMS: To investigate if
      obstacle courses, mimicking a range of police-type activities, can provide a
      suitable and valid basis for identifying fit and unfit officers and if any other
      factors may influence test performances. METHODS: Five years of GeNTOC records
      were randomly sampled, providing data for 1701 officers. Pass/fail rates were
      analysed alongside demographics and obstacle performance. RESULTS: Of 1701
      candidates, 24% (397) failed GeNTOC (7 and 42% of males and females,
      respectively). Females failed in two specific obstacles significantly more often
      than males: the 'body drag' and 'gate weave'. Errors made on these obstacles
      alone accounted for 49% of obstacle errors made by females. GeNTOC success was
      significantly associated with candidates who were male, younger, taller, heavier
      and of lower body mass index (BMI). Of all candidates, 42% were overweight, and
      8% were obese. CONCLUSIONS: The GeNTOC was not a useful screening tool and worked
      independently of BMI groups. Too few candidates were appropriately screened out;
      too many of those failing were female; and too many who passed were overweight or
      obese. GeNTOC was unfair to female candidates and favoured overweight or obese
      males. Recommendations are made to adopt alternative fitness tests or to modify
      the GeNTOC obstacles, testing procedures and data collection.

PMID- 24038509
TI  - Diet-induced obesity alters immune cell infiltration and expression of
      inflammatory cytokine genes in mouse ovarian and peri-ovarian adipose depot
      tissues.
AB  - Dysregulation of immune cells and/or altered inflammatory signaling have been
      implicated with reproductive dysfunction. Physiological changes leading to
      perturbations in the profile of immune cells and/or pro-inflammatory cytokines in
      or around female reproductive tissue could potentially have profound effects on
      ovarian function. Obesity is associated with chronic low-grade inflammation due,
      in part, to increased immune cell infiltration and inflammation in visceral
      adipose depots. This study investigated the impact of diet-induced obesity on
      immune cell infiltration and inflammation in peri-ovarian adipose tissue and mRNA
      expression of key inflammatory markers and microRNAs (miRs) in ovarian tissue.
      Six-week-old female C57Bl/6J mice were fed a standard chow or high-fat diet (HFD;
      60% kcal fat) for approximately 7 months, at which time peri-ovarian adipose
      tissue and ovarian tissues were collected. Histological analysis of peri-ovarian
      adipose tissue from obese mice revealed increased (P < 0.05) adipocyte size and
      the presence of crown-like structures, the morphological presentation of
      infiltrating immune cells in adipose tissue, along with increases (P < 0.05) in
      the mRNA levels of markers of T-cells, activated macrophages, inflammatory
      cytokines, and chemokines. Ovarian mRNA levels of Il1b, Il6, Tnfa, p55, p75,
      Ccl2, Ikbkb, and Rela were higher in obese tissue (P < 0.05), with a strong trend
      (P = 0.06) for an increase in Nos2 and RELA protein. Additionally, ovarian
      miR125b and miR143 levels were decreased (P = 0.1). These data demonstrate that
      diet-induced obesity elevates expression of inflammatory-mediator genes in both
      the ovary and surrounding adipose depot, potentially negatively affecting ovarian
      function.

PMID- 24038510
TI  - Influence of ethnicity and improved outcome of acute myeloid leukaemia: two
      decades of follow-up of Israeli patient cohort.
AB  - Acute myeloid leukaemia is a disease with unfavourable prognosis. The
      significance of various prognostic parameters is not fully understood. We studied
      293 patients to examine the influence of ethnicity and molecular markers. The
      median survival for all patients was correlated with age, white blood cell count
      and karyotype, and marginally with FLT3 internal tandem duplication. Arab
      patients were younger than Jewish patients; however, their survival was poorer
      albeit being treated with the same protocols and having more favourable
      cytogenetics. Survival rates improved over time but only for patients undergoing
      allogeneic bone marrow transplantation (alloBMT). We conclude that in our young
      patient cohort, recent improvement in survival is attributed to alloBMT therapy
      and that ethnicity affected treatment outcome.

PMID- 24038512
TI  - Bioaccumulation kinetics of polybrominated diphenyl ethers and decabromodiphenyl
      ethane from field-collected sediment in the oligochaete, Lumbriculus variegatus.
AB  - The extensive use of polybrominated diphenyl ethers (PBDEs) and decabromodiphenyl
      ethane (DBDPE) has made them widespread contaminants in abiotic environments, but
      data regarding their bioavailability to benthic organisms are sparse. The
      bioaccumulation potential of PBDEs and DBDPE from field-collected sediment was
      evaluated in the oligochaete Lumbriculus variegatus using a 49-d exposure,
      including a 28-d uptake and a 21-d elimination phase. All PBDEs and DBDPE were
      bioavailable to the worms with biota-sediment accumulation factors (BSAFs)
      ranging from 0.0210 g organic carbon/g lipid to 4.09 g organic carbon/g lipid.
      However, the bioavailability of highly brominated compounds (BDE-209 and DBDPE)
      was poor compared with that of other PBDEs, and this was confirmed by their
      relatively low freely dissolved concentrations (C(free)) measured by solid-phase
      microextraction. The inverse correlation between BSAFs and hydrophobicity was
      explained by their uptake (k(s)) and elimination (k(e)) rate constants. While ke
      changed little for PBDEs, ks decreased significantly when chemical hydrophobicity
      increased. The difference in bioaccumulation kinetics of brominated flame
      retardants in fish and the worms was explained by their physiological difference
      and the presence of multiple elimination routes. The appropriateness of 28-d
      bioaccumulation testing for BSAF estimation was validated for PBDEs and DBDPE. In
      addition, C(free) was shown to be a good indicator of bioavailability.

PMID- 24038513
TI  - Functional polymorphisms in the CD44 gene and acute myeloid leukemia cancer risk
      in a Chinese population.
AB  - CD44 is such one adhesion molecule that mediates interactions between acute
      myeloid leukemia (AML) cells and stromal. It has been demonstrated that CD4 plays
      a critical role in AML development. However, studies of functional single
      nucleotide polymorphisms (SNPs) in CD44 gene have not touched upon AML. This case
      control study probed the contribution of functional SNPs in CD44 gene to AML
      susceptibility in eastern Chinese population. Five representative SNPs of CD44
      (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were opted
      and genotyped in 421 AML patients and 461 healthy subjects and the association
      with risk of AML was estimated by logistic regression. Moreover, the potential
      role of rs13347C > T in AML was further explored. Compared with the rs13347CC
      genotype, CT carriers had a significant increase in AML susceptibility (adjusted
      odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.32-2.34), TT carriers
      had a further increased risk of AML (OR = 2.67; 95% CI = 1.69-4.21). Furthermore,
      our transient transfection assay and Western blot results demonstrated that the
      presence of rs13347T allele led to more CD44 expression. Yet, there exists no
      significant difference in genotype frequencies of the other four sites between
      cases and controls. Above findings suggest that rs13347C>T in 3'UTR of CD44 may
      be a genetic modifier for developing AML.

PMID- 24038514
TI  - Inducible displacements of the cup and the femoral head during active range of
      motion: dynamic RSA studies of cemented total hip replacements.
AB  - We evaluated changes in position of the femoral head relative to the cup and of
      the cup relative to the pelvis in total hip replacement patients during hip
      motion 2 years postoperatively. Two patient groups with nine patients in each
      group were studied. Hip motions, translations of the femoral head center, and cup
      displacements were recorded with dynamic radiostereometric examination (RSA, 2
      exposures/s) during abduction in Group 1 and with use of static RSA exposures at
      increasing flexion of the hip in Group 2. Conventional radiographic examinations
      were used to evaluate any radiolucent lines around the cups at 2 years. During
      active abduction the femoral head center moved medially (median 0.04 mm) and the
      cup tilted anteriorly (median 0.09 mm). Increments in radiolucent lines at 2
      years correlated to medial femoral head penetration, posterior tilt, and
      retroversion of the cup at 20 degrees  of abduction. The extension of radiolucent
      lines at 2 years showed a positive correlation with proximal inducible
      displacement of the cup and posterior translation of the femoral head center at
      maximum hip flexion. Our observations may be of value in understanding the
      pathogenesis of the loosening process and may be used to facilitate the
      development of prosthetic designs that optimize hip kinematics.

PMID- 24038515
TI  - Reinnervation of segmented latissimus dorsi muscle with the distal stump of the
      thoracodorsal nerve: A preliminary experimental study in rats.
AB  - To date, nerve stumps have been dissected at the proximal side of the donor
      muscle for reinnervation of the muscle in free neurovascular muscle transfer.
      Herein, we examined the use of the distal thoracodorsal nerve, dissected from the
      muscle belly at the distal side of the latissimus dorsi muscle, for the
      reinnervation of muscle. The rat right latissimus dorsi muscle was employed as
      the model for our study. Twenty Wistar rats were used in this study. A
      rectangular muscle segment was dissected with the distal stump of dominant
      thoracodorsal nerve. After rotation of muscle, the distal nerve stump was sutured
      to a severed proximal recipient thoracodorsal nerve (n = 5). The degree of
      reinnervation through the distal nerve stump was compared with control groups
      that received proximal-to-proximal nerve sutures (n = 5), nerves that were not
      severed (n = 5), and severed nerves that were not sutured (n = 5) using
      electrophysiological, histological, and muscular volume assessments.
      Reinnervation of the distal nerve stump was confirmed by the contraction of the
      muscle following electrical stimulation and electromyography. Crossing of axons
      into motor endplates was confirmed by histology. Results of these assays were
      similar to that of the proximal nerve suture group. The volume of muscle in the
      distal nerve suture group was not significant different from that of the proximal
      nerve suture group (P = 0.63). It was demonstrated that the distal stump of the
      thoracodorsal nerve can be used to innervate segmented latissimus dorsi muscle.
      This novel procedure for the reinnervation of transplanted muscle deserves
      further investigations.

PMID- 24038516
TI  - Amygdala excitability to subliminally presented emotional faces distinguishes
      unipolar and bipolar depression: an fMRI and pattern classification study.
AB  - BACKGROUND: Bipolar disorder and Major depressive disorder are difficult to
      differentiate during depressive episodes, motivating research for differentiating
      neurobiological markers. Dysfunctional amygdala responsiveness during emotion
      processing has been implicated in both disorders, but the important rapid and
      automatic stages of emotion processing in the amygdala have so far never been
      investigated in bipolar patients. METHODS: fMRI data of 22 bipolar depressed
      patients (BD), 22 matched unipolar depressed patients (MDD), and 22 healthy
      controls (HC) were obtained during processing of subliminal sad, happy and
      neutral faces. Amygdala responsiveness was investigated using standard univariate
      analyses as well as pattern-recognition techniques to differentiate the two
      clinical groups. Furthermore, medication effects on amygdala responsiveness were
      explored. RESULTS: All subjects were unaware of the emotional faces. Univariate
      analysis revealed a significant group * emotion interaction within the left
      amygdala. Amygdala responsiveness to sad>neutral faces was increased in MDD
      relative to BD. In contrast, responsiveness to happy>neutral faces showed the
      opposite pattern, with higher amygdala activity in BD than in MDD. Most of the
      activation patterns in both clinical groups differed significantly from
      activation patterns of HC--and therefore represent abnormalities. Furthermore,
      pattern classification on amygdala activation to sad>happy faces yielded almost
      80% accuracy differentiating MDD and BD patients. Medication had no significant
      effect on these findings. CONCLUSIONS: Distinct amygdala excitability during
      automatic stages of the processing of emotional faces may reflect differential
      pathophysiological processes in BD versus MDD depression, potentially
      representing diagnosis-specific neural markers mostly unaffected by current
      psychotropic medication.

PMID- 24038517
TI  - Joining the fingers: a HOXD13 Story.
AB  - Synpolydactyly (SPD, OMIM 186000) is a rare congenital limb disorder
      characterized by syndactyly between the third and fourth fingers and between the
      fourth and fifth toes, with partial or complete digit duplication in the
      syndactylous web. The majority of these anomalies co-segregate with mutations in
      the HOXD13 gene,a homeobox transcription factor crucial for distal limb
      development. Different classes of HOXD13 mutations are involved in the
      pathogenesis of synpolydactyly, but an unequivocal genotype-phenotype correlation
      cannot always be achieved due to the clinical heterogeneity and reduced
      penetrance of SPD. All mutations identified so far mapped to the N-terminal
      polyalanine tract or to the C-terminal homeodomain of HOXD13,causing typical or
      atypical features of SPD, respectively. However, mutations outside of these
      domains cause a broad variety of clinical features that complicate the
      differential diagnosis. The existing animal models that are currently used to
      study HOXD13 (mal)function are therefore instrumental in unraveling potential
      genotype-phenotype correlations. Both mouse- and chick-based approaches allow the
      in vivo study of the pathogenic mechanism by which HOXD13 mutations cause SPD
      phenotypes as well as help in identifying the transcriptional targets.

PMID- 24038518
TI  - Reappraisal of the anatomical landmarks of motor and premotor cortical regions
      for image-guided brain navigation in TMS practice.
AB  - Image-guided navigation systems dedicated to transcranial magnetic stimulation
      (TMS) have been recently developed and offer the possibility to visualize
      directly the anatomical structure to be stimulated. Performing navigated TMS
      requires a perfect knowledge of cortical anatomy, which is very variable between
      subjects. This study aimed at providing a detailed description of sulcal and
      gyral anatomy of motor cortical regions with special interest to the inter
      individual variability of sulci. We attempted to identify the most stable
      structures, which can serve as anatomical landmarks for motor cortex mapping in
      navigated TMS practice. We analyzed the 3D reconstruction of 50 consecutive
      healthy adult brains (100 hemispheres). Different variants were identified
      regarding sulcal morphology, but several anatomical structures were found to be
      remarkably stable (four on dorsoventral axis and five on rostrocaudal axis).
      These landmarks were used to define a grid of 12 squares, which covered motor
      cortical regions. This grid was used to perform motor cortical mapping with
      navigated TMS in 12 healthy subjects from our cohort. The stereotactic
      coordinates (x-y-z) of the center of each of the 12 squares of the mapping grid
      were expressed into the standard Talairach space to determine the corresponding
      functional areas. We found that the regions whose stimulation produced almost
      constantly motor evoked potentials mainly correspond to the primary motor cortex,
      with rostral extension to premotor cortex and caudal extension to posterior
      parietal cortex. Our anatomy-based approach should facilitate the expression and
      the comparison of the results obtained in motor mapping studies using navigated
      TMS.

PMID- 24038519
TI  - Syntheses and biological activities of new hybrid molecules containing different
      heterocyclic moieties.
AB  - 4-Aryl-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-(thi)oles 5-7, obtained starting from
      nicotinic acid hydrazide were converted to the corresponding Mannich bases 12-24
      by the reaction with several heterocyclic amines in the presence of formaldehyde.
      The synthesis of S-alkylated compounds 8-11 was performed from the reaction of
      the corresponding triazol-5-thioles with various alkyl halides. The condensation
      of carbo(thio)amides 2-4 with 4-chlorophenacyl bromide afforded the corresponding
      1,3-thia(oxa)zol-2(3H)-ylidene]pyridine-3-carbohydrazides 25-27. 1,3
      Thia(oxa)zolidine derivatives 28-30 were obtained from the cyclization reaction
      between compounds 2-4 and ethyl bromoacetate. All newly synthesized compounds
      were screened for their antimicrobial, antiurease, and antilipase activities. The
      biological activity studies revealed that all the compounds screened showed good
      or moderate antimicrobial, antiurease, and/or antilipase activity. 

PMID- 24038520
TI  - Immediate effect of transcranial direct current stimulation on postural stability
      and functional mobility in Parkinson's disease.

PMID- 24038521
TI  - Loss of p53 cooperates with K-ras activation to induce glioma formation in a
      region-independent manner.
AB  - Gliomas are recognized as a heterogeneous group of neoplasms differing in their
      location and morphological features. These differences, between and within
      varying grades of gliomas, have not been explained solely on the grounds of an
      oncogenic stimulus. Interactions with the tumor microenvironment as well as
      inherent characteristics of the cell of origin are likely a source of this
      heterogeneity. There is an ongoing debate over the cell of origin of gliomas,
      where some suggest a progenitor, while others argue for a stem cell origin. Thus,
      it is presumed that neurogenic regions of the brain such as the subventricular
      zone (SVZ) containing large numbers of neural stem and progenitor populations are
      more susceptible to transformation. Our studies demonstrate that K-ras(G12D)
      cooperates with the loss of p53 to induce gliomas from both the SVZ and cortical
      region, suggesting that cells in the SVZ are not uniquely gliomagenic. Using
      combinations of doxycycline-inducible K-ras(G12D) and p53 loss, we show that
      tumors induced by the cooperative actions of these genes remain dependent on
      active K-ras expression, as deinduction of K-ras(G12D) leads to complete tumor
      regression despite absence of p53. These results suggest that the interplay
      between specific combinations of genetic alterations and susceptible cell types,
      rather than the site of origin, are important determinates of gliomagenesis.
      Additionally, this model supports the view that, although several genetic events
      may be necessary to confer traits associated with oncogenic transformation,
      inactivation of a single oncogenic partner can undermine tumor maintenance,
      leading to regression and disease remission.

PMID- 24038522
TI  - Edge-selectively sulfurized graphene nanoplatelets as efficient metal-free
      electrocatalysts for oxygen reduction reaction: the electron spin effect.
AB  - To replace precious platinum (Pt)-based electrocatalysts for cathodic oxygen
      reduction reaction (ORR), edge-selectively sulfurized graphene nanoplatelets
      (SGnP) are synthesized as efficient metal-free electrocatalysts simply by ball
      milling pristine graphite in the presence of sulfur (S8 ). The resultant SGnPs
      exhibit remarkable electrocatalytic activity toward ORR with better tolerance to
      methanol crossover/CO poisoning effects and longer-term stability than those of
      pristine graphite and commercial Pt/C electrocatalysts. Edge-Selectively
      Sulfurized Graphene Nanoplatelets as Efficient Metal-Free Electrocatalysts for
      Oxygen Reduction Reaction: The Electron Spin Effect. 

PMID- 24038523
TI  - Three-dimensional macroporous NiCo(2)O(4) sheets as a non-noble catalyst for
      efficient oxygen reduction reactions.
AB  - A facile and low-cost strategy is developed to prepare three-dimensional (3D)
      macroporous NiCo2 O4 sheets, which can be used as a highly efficient non-noble
      metal electrocatalyst for the oxygen reduction reaction (ORR) in alkaline
      conditions. The as-obtained sheets have a thickness of about 150 nm and feature a
      typical 3D macroporous structure with pore volumes of up to 0.23 cm(3)  g(-1) ,
      which could decrease the mass transport resistance and allow easier access of the
      reactants to the active surface sites. The as-prepared macroporous NiCo2 O4
      sheets exhibit high electrocatalytic activity for ORR with a four-electron
      pathway, good long-term stability and high tolerance against methanol. The unique
      3D macroporous structure and intrinsic properties may be responsible for their
      high performance. 

PMID- 24038524
TI  - Identifying health insurance predictors and the main reported reasons for being
      uninsured among US immigrants by legal authorization status.
AB  - This study identifies differences in health insurance predictors and investigates
      the main reported reasons for lacking health insurance coverage between short
      stayed (<= 10 years) and long-stayed (>10 years) US immigrant adults to parse the
      possible consequences of the Affordable Care Act among immigrants by length of
      stay and documentation status. Foreign-born adults (18-64 years of age) from the
      2009 California Health Interview Survey are the study population. Health
      insurance coverage predictors and the main reasons for being uninsured are
      compared across cohorts and by documentation status. A logistic-regression two
      part multivariate model is used to adjust for confounding factors. The analyses
      determine that legal status is a strong health insurance predictor, particularly
      among long-stayed undocumented immigrants. Immigration status is the main
      reported reason for lacking health insurance. Although long-stayed documented
      immigrants are likely to benefit from the Affordable Care Act implementation,
      undocumented immigrants and short-stayed documented immigrants may encounter
      difficulties getting health insurance coverage.

PMID- 24038525
TI  - Psychological morbidity and stress but not social factors influence level of fear
      of cancer recurrence in young women with early breast cancer: results of a cross
      sectional study.
AB  - BACKGROUND: Fear of cancer recurrence (FCR) is a common problem amongst
      survivors. Past research has shown that young women with breast cancer are
      particularly vulnerable to FCR, yet few previous studies have specifically
      examined FCR in this subgroup. AIMS: The aim of the study is to explore the
      relationship between FCR, psychological morbidity and social factors. A secondary
      aim was to explore the relationship between clinical levels of FCR and
      generalised anxiety disorder (GAD) and hypochondriasis. METHOD: Two hundred
      eighteen breast cancer survivors (aged 18-45 years at diagnosis) diagnosed at
      least 1 year prior were recruited through seven metropolitan oncology clinics and
      two breast cancer consumer groups. Participants completed a web-based
      questionnaire, which assessed FCR, psychological functioning, generalised
      anxiety, hypochondriasis and items exploring past cancer-related experiences,
      attitudes to future childbearing, social support and correlates were identified
      using linear regression. RESULTS: Psychological morbidity scales measuring
      anxiety and psychological functioning and stressful life events were
      significantly associated with FCR in adjusted and unadjusted models (p < 0.0001).
      Past cancer experiences, children, social support and attitudes to childrearing
      were not associated with FCR. Among those with clinical levels of FCR (n = 152),
      43% met screening criteria for hypochondriasis, and 36% met screening criteria
      for GAD. CONCLUSIONS: This study shows psychological morbidity is associated with
      FCR, but the majority of women with high levels of FCR do not also meet the
      criteria for a clinical level of GAD or hypochondriasis. Understanding the
      factors that make young women vulnerable to FCR is important to help guide the
      development of FCR-specific interventions for this subgroup.

PMID- 24038526
TI  - Recent advances in the field of main-group mono- and diatomic "allotropes"
      stabilised by neutral ligands.
AB  - The study of ligand stabilised mono- and diatomic zero oxidation state complexes
      is a young and fascinating topic. This area merges the fields of low-oxidation
      state main-group chemistry, homoatomic multiple bonding and fundamental
      coordination chemistry. As with a great deal of recent coordination chemistry
      within the d-block, carbene ligands are clearly the star of the show,
      highlighting their importance within the p-block as well. This Minireview focuses
      on the significant developments of the past two years. 

PMID- 24038527
TI  - Changes in WNT signaling-related gene expression associated with development and
      cloning in bovine extra-embryonic and endometrial tissues during the peri
      implantation period.
AB  - We determined if somatic cell nuclear transfer (SCNT) cloning is associated with
      WNT-related gene expression in cattle development, and if the expression of genes
      in the WNT pathway changes during the peri-implantation period. Extra-embryonic
      and endometrial tissues were collected at gestation days 18 and 34 (d18, d34).
      WNT5A, FZD4, FZD5, LRP5, CTNNB1, GNAI2, KDM1A, BCL2L1, and SFRP1 transcripts were
      localized in extra-embryonic tissue, whereas SFRP1 and DKK1 were localized in the
      endometrium. There were no differences in the localization of these transcripts
      in extra-embryonic tissue or endometrium from SCNT or artificial insemination
      (AI) pregnancies. Expression levels of WNT5A were 11-fold greater in the
      allantois of SCNT than AI samples. In the trophoblast, expression of WNT5A, FZD5,
      CTNNB1, and DKK1 increased significantly from d18 to d34, whereas expression of
      KDM1A and SFRP1 decreased, indicating that implantation is associated with major
      changes in WNT signaling. SCNT was associated with altered WNT5A expression in
      trophoblasts, with levels increasing 2.3-fold more in AI than SCNT conceptuses
      from d18 to d34. In the allantois, expression of WNT5A increased 6.3-fold more in
      SCNT than AI conceptuses from d18 to d34. Endometrial tissue expression levels of
      the genes tested did not differ between AI or SCNT pregnancies, although
      expression of individual genes showed variation across developmental stages. Our
      results demonstrate that SCNT is associated with altered expression of specific
      WNT-related genes in extra-embryonic tissue in a time- and tissue-specific
      manner. The pattern of gene expression in the WNT pathway suggests that
      noncanonical WNT signal transduction is important for implantation of cattle
      conceptuses.

PMID- 24038528
TI  - Programmed death 1 and B and T lymphocyte attenuator immunoreceptors and their
      association with malignant T-lymphoproliferative disorders: brief review.
AB  - Malignant T-cell lymphoproliferative diseases are relatively rare. T cells are
      activated through the T-cell receptor with the aid of costimulating molecules
      that can be either excitatory or inhibitory. Such pathways have been also
      implicated in mechanisms of malignant T-cell lymphoproliferative diseases'
      persistence and relapse by circumventing immune responses. To date, three major
      immunoinhibitory molecules have been recognized, namely programmed cell death-1
      (PD-1), B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte antigen 4
      (CTLA-4). Although CTLA-4 is considered the 'gatekeeper' of immune tolerance, PD
      1 negatively regulates immune responses broadly, whereas BTLA activation has been
      shown to inhibit CD8+ cancer-specific T cells. Both PD-1 and BTLA downregulate
      proximal T-cell receptor signalling cascade and are involved in immune evasion of
      leukaemias and lymphomas, even after allogeneic stem cell transplantation. These
      immunoregulatory molecules can have seemingly a synergistic effect on weakening
      the immune response of patients with haematological malignancies, and their
      manipulation represents a very active field of preclinical as well as clinical
      interest.

PMID- 24038529
TI  - Diffusion-weighted imaging of the high-risk breast: Apparent diffusion
      coefficient values and their relationship to breast density.
AB  - PURPOSE: To document the apparent diffusion coefficient (ADC) of fibroglandular
      breast tissue in women at high-risk of developing breast cancer and investigate
      the relationship between ADC and breast density. MATERIALS AND METHODS: Local
      research ethics approval was obtained. A total of 33 high-risk women including 17
      BRCA1/2 mutation carriers (mean age, 43 years) and 16 women postmantle
      irradiation (mean age 40 years) underwent diffusion-weighted MRI between days 6
      and 16 of their menstrual cycle. ADC histograms from a region of interest in
      fibroglandular tissue and mammographic breast density measurements were obtained.
      Mean, percentile ADC values (10th, 25th, 50th, 75th, 90th) and skew were compared
      for the two groups; ADC and mammographic breast density were correlated. RESULTS:
      Mean ADC values (*10(-6) mm(2) /s) were 2017 +/- 197 in postmantle irradiated
      women and 1827 +/- 289 in BRCA1/2 mutation carriers (P = 0.035) with significant
      differences at all percentiles (P < 0.0001) but not skew (P = 0.44). ADC values
      showed weak positive correlation with mammographic breast density in BRCA1/2
      mutation carriers (r = 0.51, P = 0.043) but not in postmantle radiotherapy
      patients (r = 0.49, P = 0.13). CONCLUSION: Higher ADC values seen in
      fibroglandular tissue postmantle irradiation compared with BRCA1/2 mutation
      carriers has potential to improve tumor detection in these patients. Lack of
      correlation between ADC and breast density postmantle irradiation may be a result
      of microstructural changes.

PMID- 24038530
TI  - Cross-link stabilization does not affect the response of collagen molecules,
      fibrils, or tendons to tensile overload.
AB  - We investigated whether immature allysine-derived cross-links provide
      mechanically labile linkages by exploring the effects of immature cross-link
      stabilization at three levels of collagen hierarchy: damaged fibril morphology,
      whole tendon mechanics, and molecular stability. Tendons from the tails of young
      adult steers were either treated with sodium borohydride (NaBH4) to stabilize
      labile cross-links, exposed only to the buffer used during stabilization
      treatment, or maintained as untreated controls. One-half of each tendon was then
      subjected to five cycles of subrupture overload. Morphologic changes to collagen
      fibrils resulting from overload were investigated using scanning electron
      microscopy, and changes in the hydrothermal stability of collagen molecules were
      assessed using hydrothermal isometric tension testing. NaBH4 cross-link
      stabilization did not affect the response of tendon collagen to tensile overload
      at any of the three levels of hierarchy studied. Cross-link stabilization did not
      prevent the characteristic overload-induced mode of fibril damage that we term
      discrete plasticity. Similarly, stabilization did not alter the mechanical
      response of whole tendons to overload, and did not prevent an overload-induced
      thermal destabilization of collagen molecules. Our results indicate that
      hydrothermally labile cross-links may not be as mechanically labile as was
      previously thought.

PMID- 24038531
TI  - Second free radial forearm flap for urethral reconstruction after partial flap
      necrosis of tube-in-tube phalloplasty with radial forearm flap: a report of two
      cases.
AB  - We present a salvage procedure to reconstruct the neo-urethra after partial flap
      necrosis occurring in free radial forearm flap (RFF) phalloplasty for sex
      reassignment surgery. Two cases of tube-in-tube phalloplasty using a free sensate
      RFF are described in which partial flap necrosis occurred involving the complete
      length of the neo-urethra and a strip of the outer lining of the neo-phallus. Neo
      urethra-reconstruction was performed with a second RFF from the contralateral
      side providing well-vascularized tissue. No flap-related complications were
      observed. Twelve months postoperatively, both patients were able to void while
      standing. A satisfactory aesthetic appearance of the neo-phallus could be
      preserved with an excellent tactile and erogenous sensitivity. Using this
      technique, we successfully salvaged the neo-urethra and reconstructed the outer
      lining of the neo-phallus

PMID- 24038532
TI  - Effects of a chronic lower range of triclosan exposure on a stream mesocosm
      community.
AB  - Triclosan (5-chloro-2-(2,4-dichlorophenoxy)phenol) is an antimicrobial found in
      consumer soaps and toothpaste. It is in treated wastewater effluents at low parts
      per-billion concentrations, representing a potentially chronic exposure condition
      for biota inhabiting receiving streams. For the present study, a naturally
      colonized benthos was created using flow-through indoor mesocosms; then, the
      benthic communities were dosed to achieve different in-stream triclosan
      concentrations (control, 0.1 MUg/L, 0.5 MUg/L, 1.0 MUg/L, 5.0 MUg/L, and 10
      MUg/L) for 56 d. Water quality parameters and endpoints from bacteria to
      macroinvertebrates, as well as interacting abiotic components, were measured.
      Effects of triclosan on specific microbial endpoints were observed at all doses,
      including an effect on litter decomposition dynamics at doses of 1.0 MUg/L and
      higher. Resistance of periphytic bacteria to triclosan significantly increased at
      doses of 0.5 MUg/L and above. By the end of dosing, the antimicrobial appeared to
      stimulate the stream periphyton at the 3 lowest doses, while the 2 highest doses
      exhibited decreased stocks of periphyton, including significantly lower bacteria
      cell densities and cyanobacteria abundance compared with the control. Other than
      an effect on benthic ostracods, the changes that occurred in the periphyton did
      not translate to significant change in the colonizing nematodes, the
      macroinvertebrate community as a whole, or other measurements of stream function.
      The results shed light on the role a low, chronic exposure to triclosan may play
      in effluent-dominated streams.

PMID- 24038533
TI  - Patterns of nodal involvement for clinically N0 salivary gland carcinoma:
      refining the role of elective neck irradiation.
AB  - BACKGROUND: The purpose of this study was to analyze the pattern of occult
      cervical lymph node metastasis among patients with clinically N0 salivary gland
      carcinoma. METHODS: One hundred nineteen patients underwent primary surgery and
      ipsilateral neck dissection for clinically N0 carcinomas of the major and minor
      salivary glands. Eighty patients (67%) had parotid tumors. Distribution of T
      classification was: T1 (18%), T2 (28%), T3 (23%), and T4 (32%). RESULTS: Twenty
      five patients (21%) had pathological cervical disease. The incidence was highest
      among patients with adenocarcinoma (35%) and high-grade mucoepidermoid carcinoma
      (35%). The most common site of cervical lymph node metastasis was level II (71%),
      followed by level III (15%), and level IB (8%). On multivariate analysis,
      histological subtype was independently predictive of occult pathological lymph
      node metastasis (p < .001). CONCLUSION: The likelihood of occult cervical lymph
      node metastasis for patients with salivary gland carcinoma is driven
      predominantly by histological subtype. Implications for elective neck irradiation
      are discussed.

PMID- 24038535
TI  - Non-innocent ligand effects on low-oxidation-state indium complexes.
AB  - Attempts to coordinate neutral ligands to low oxidation state indium centers are
      often hindered by disproportionation pathways that produce elemental indium and
      higher oxidation state species. In contrast, we find that reactions of the salt,
      InOTf (OTf=trifluoromethanesulfonate), with alpha-diimine ligands yielded
      intensely colored compounds with no evidence of decomposition. X-ray structural
      analysis of InOTf?(Mes) DAB(Me) ((Mes) DAB(Me) =N,N-dimesityl-2,3-dimethyl
      diazabutadiene; 1) reveals a discrete molecular compound with a pyramidal
      coordination environment at the indium center, consistent with the presence of a
      stereochemically active lone pair of electrons on indium and a neutral
      diazabutadiene chelate ligand. The use of the less-electron-rich (Mes) DAB(H)
      ligand ((Mes) DAB(H) =N,N-dimesityl-diazabutadiene) engenders dramatically
      different reactivity and produces a metallopolymer (InOTf?(Mes) DAB(H) )infinity
      (2) linked via C?C and In?In bonds. The difference in reactivity is rationalized
      by cyclic voltammetry and DFT studies that suggest more facile electron transfer
      from In(I) to the (Mes) DAB(H) and bis(aryl)acenaphthenequinonediimine (BIAN)
      ligands. Solution EPR spectroscopy indicates the presence of non-interacting
      ligand-based radicals in solution, whereas solid-state EPR studies reflect the
      presence of a thermally accessible spin triplet consistent with reversible C?C
      bond cleavage. 

PMID- 24038536
TI  - The ulnar nerve consistently drives flexion of the middle finger.

PMID- 24038534
TI  - Constitutive Stat3 activation alters behavior of hair follicle stem and
      progenitor cell populations.
AB  - STATs play crucial roles in a wide variety of biological functions, including
      development, proliferation, differentiation and migration as well as in cancer
      development. In the present study, we examined the impact of constitutive
      activation of Stat3 on behavior of keratinocytes, including keratinocyte stem
      cells (KSC) in vivo. BK5.Stat3C transgenic (Tg) mice, which express a
      constitutively active form of Stat3 (Stat3C) in the basal layer of the epidermis
      and in the bulge region KSCs exhibited a significantly reduced number of
      CD34+/alpha6 integrin+ cells compared to non-transgenic (NTg) littermates. There
      was a concomitant increase in the Lgr-6, Lrig-1, and Sca-1 populations in the Tg
      mice in contrast to the CD34 and Keratin-15 positive population. In addition,
      increased expression of c-myc, beta-catenin, and epithelial-mesenchymal
      transition (EMT)-related genes as well as decreased expression of alpha6-integrin
      was observed in the hair follicles of Tg mice. Notably, Sca-1 was found to be a
      direct transcriptional target of Stat3 in keratinocytes. The current data suggest
      that elevated Stat3 activity leads to depletion of hair follicle KSCs along with
      a concomitant increase of stem/progenitor cells above the bulge region. Overall,
      the current data indicate that Stat3 plays an important role in keratinocyte
      stem/progenitor cell homeostasis.

PMID- 24038537
TI  - Primary excision of the ulnar head for fractures of the distal ulna associated
      with fractures of the distal radius in severe osteoporotic patients.
AB  - We performed primary excision of the ulnar head on 23 patients over 70 years of
      age with severe comminuted fractures of both the distal radius and ulna. The
      distal radius fracture was fixed rigidly with a volar locking plate, and the
      ulnar head was resected at the fracture site. All the distal radial fractures
      united without major complications. The mean wrist flexion/extension arc was 122
      degrees , the mean pronation/supination arc was 164 degrees , and grip strength
      was 69% of that on the contralateral side. All patients returned to their daily
      activities within a short time without any additional surgical treatment. For
      elderly patients, primary excision of the ulnar head is an effective treatment
      for comminuted distal radius and ulna fractures. 

PMID- 24038538
TI  - The value of different inflammatory markers in distinguishing deep closed hand
      infections from non-infective causes.

PMID- 24038539
TI  - Age-related increases in Stroop interference: delineation of general slowing
      based on behavioral and white matter analyses.
AB  - The Stroop interference task is a widely used paradigm to examine cognitive
      inhibition, which is a key component of goal-directed behavior. With increasing
      age, reaction times in the Stroop interference task are usually slowed. However,
      to date it is still under debate if age-related increases in reaction times are
      merely an artifact of general slowing. The current study was conducted to
      investigate the role of general slowing, as measured by Trail-Making-Test-A, in
      age-related alterations of Stroop interference. We applied Diffusion Tensor
      Imaging (DTI) to determine the topography of neuronal networks underlying Stroop
      interference under control of general slowing. On the behavioral level, linear
      regression analysis demonstrated that age accounted for significant variance on
      Stroop interference, whereas TMT-A performance did not. Controlling for TMT-A,
      DTI based white matter analyses demonstrated a strong association of Stroop
      interference with integrity measures of genu of corpus callosum, bilateral
      anterior corona radiata, and bilateral anterior limb of capsula interna. These
      pathways are associated with frontal brain regions by either connecting the
      bilateral dorsolateral prefrontal cortex or the anterior cingulate cortex with
      frontal and subcortical regions or by containing fibers which are part of cortico
      thalamic circuits that cross prefrontal regions. Importantly, results expand our
      knowledge of the neural basis of Stroop interference and emphasize the importance
      of white matter integrity of frontal pathways in the modulation of Stroop
      interference. Combining behavioral and DTI findings our results further suggest
      that cognitive inhibition, as measured by Stroop task, is a qualitatively
      distinct cognitive process that declines with age.

PMID- 24038540
TI  - Microhealth insurance and the risk coping strategies for the management of
      illness in Karnataka: a case study.
AB  - Risk coping strategies adopted by the households in the event of illness depends
      on the accessibility to healthcare financing mechanisms including health
      insurance. The empirical evidence on the effect of microhealth insurance (MHI) on
      the risk coping strategies of the households is scarce. This paper evaluates the
      impact of Sampoorna Suraksha Program, a nongovernmental organization-initiated
      MHI scheme and the risk coping strategies of households faced with medical
      illness in Karnataka state, India. In this descriptive cross-sectional study, we
      collected data from 416 insured households, 366 newly insured households and 364
      uninsured households in randomly selected 10 taluks in three districts of
      Karnataka state, India. We hypothesized that insured individuals rely less on ex
      post risk coping strategies (borrowing, use of savings and sale of assets)
      compared with uninsured and newly insured individuals. Our hypothesis was tested
      using logistic and linear regression analysis. A significant difference among
      insured, uninsured and newly insured individuals was found for borrowing but not
      in the use of savings or sale of assets. A positive impact of MHI on illness
      induced borrowing (both incidence and amount) was evident. The evidence from this
      study reinforces the role of MHI as a pivotal financing alternative to out-of
      pocket expenditure in India.

PMID- 24038541
TI  - Enhancing preparedness and satisfaction of caregivers of patients discharged from
      an inpatient rehabilitation facility using an interactive website.
AB  - PURPOSE: Research indicates a need for improved caregiver preparation to provide
      care following a patient's discharge from inpatient rehabilitation. The aim of
      this project was to test the use of web-based resources to enhance the
      preparedness and satisfaction of such caregivers. METHODS: A website was provided
      to caregivers with resources and e-mail access to a rehabilitation nurse
      practitioner. Care recipients had the following diagnoses: stroke, amputation,
      trauma/orthopedic, brain injury or debility. Preparedness for caregiving was
      assessed before utilization of the website and after discharge. Satisfaction of
      the resources was assessed after discharge. Measures included the Preparedness
      for Caregiver Scale and the Client Satisfaction Questionnaire. Seventy caregivers
      completed the predischarge preparedness tool. Thirty returned both tools
      postdischarge. FINDINGS: Analysis of pre-post test data indicated increased
      preparedness to provide care after resource use, no increase meeting the
      caregiver's personal needs, and satisfaction with the resources provided. The
      caregivers of brain-injured patients reported less preparation as caregivers than
      those who cared for patients with other diagnoses. Although high interest was
      reported in using e-mail with the nurse practitioner, the resource was not
      utilized. CLINICAL RELEVANCE: This preliminary study supports the clinical
      relevance of Internet resources to improve caregiver preparation. With shortened
      hospital stays, providing applicable and evidence-based websites and other online
      services for caregivers can complement other healthcare services. More research
      focused on preparing caregivers and supporting personal caregiver needs is needed
      to evaluate the impact on overall rehabilitation outcomes.

PMID- 24038542
TI  - Venous coupler size in autologous breast reconstruction--does it matter?
AB  - BACKGROUND: Autologous microvascular breast reconstruction is an increasingly
      common procedure. While arterial anastomoses are traditionally being hand-sewn,
      venous anastomoses are often completed with a coupler device. The largest coupler
      size possible should be used, as determined by the smaller of either the donor or
      recipient vein. While its efficacy has been shown using 3.0-mm size and greater
      couplers, little is known about the consequences of using coupler sizes less than
      or equal to 2.5 mm. METHODS: A retrospective chart review of patients undergoing
      autologous breast reconstruction was conducted at NYU Medical Center between
      November 2007 and November 2011. Flaps were divided into cohorts based on coupler
      size used: 2.0 mm, 2.5 mm, and 3.0 mm. Outcomes included incidence of arterial or
      venous insufficiency, hematoma, fat necrosis, partial flap loss, full flap loss,
      and need for future fat grafting. RESULTS: One-hundred ninety-seven patients
      underwent 392 flaps during the study period. Patients were similar in age, type
      of flap, smoking status, and radiation history. Coupler size less than or equal
      to 2.0 mm was found to be a significant risk factor for venous insufficiency (P =
      0.038), as well as for development of fat necrosis (P = 0.041) and future need
      for fat grafting (P = 0.050). In multivariate analysis, body mass index was found
      to be an independent risk factor for skin flap necrosis (P = 0.010) and full flap
      loss (P = 0.035). CONCLUSIONS: Complications were significantly increased in
      patients where couplers of 2.0 mm or less were used, therefore to be avoided
      whenever possible. When needed, more aggressive vessel exposure through rib
      harvest, the use of thoracodorsal vessels or hand-sewing the anastomosis should
      be considered in cases of internal mammary vein caliber of 2.0 mm or less.
      CLINICAL QUESTION: Therapeutic. LEVEL OF EVIDENCE: Level III.

PMID- 24038543
TI  - Prominent extensor truncal dystonia in Egyptian patients with Wilson's disease.

PMID- 24038544
TI  - Reliability of two-dimensional and three-dimensional pseudo-continuous arterial
      spin labeling perfusion MRI in elderly populations: comparison with 15O-water
      positron emission tomography.
AB  - PURPOSE: To investigate the reliability and accuracy of two pseudo-continuous
      arterial spin labeling (pCASL) sequences, using two-dimensional (2D) gradient
      echo echo planar imaging (EPI) and 3D gradient and spin echo (GRASE) as the
      readout, respectively. MATERIALS AND METHODS: Each sequence was performed twice 4
      weeks apart on six normal control subjects, six elderly subjects with mild
      cognitive impairment (MCI), and one participant with Alzheimer's disease (AD).
      Eight of these subjects also underwent H2 (15) O positron emission tomography
      (PET) scans on the same day or proximal to their second MRI scan. The
      longitudinal repeatability of EPI and GRASE pCASL were evaluated with the
      intraclass correlation coefficient (ICC) and within-subject coefficient of
      variation (wsCV). RESULTS: The ICCs of global perfusion measurements were 0.697
      and 0.413 for GRASE and EPI based pCASL respectively. GRASE pCASL also
      demonstrated a higher longitudinal repeatability for regional perfusion
      measurements across 24 regions-of-interests (ICC = 0.707; wsCV = 10.9%) compared
      with EPI pCASL (ICC = 0.362; wsCV = 15.3%). When compared with PET, EPI pCASL
      showed a higher degree of spatial correlation with PET than GRASE pCASL, although
      the difference was not statistically significant. CONCLUSION: The 3D GRASE pCASL
      offers better repeatability than 2D EPI pCASL, thereby may provide a reliable
      imaging marker for the evaluation of disease progression and treatment effects in
      MCI and early AD subjects.

PMID- 24038545
TI  - The evolution of psychological distress trajectories in women diagnosed with
      advanced breast cancer: a longitudinal study.
AB  - BACKGROUND: Anxiety and depression (distress) over the first year following the
      initial adjuvant therapy for advanced breast cancer (ABC) remain poorly
      documented in non-Caucasian populations. This study describes trajectories of
      distress and their determinants in Chinese women with ABC. METHODS: Of the 228
      Chinese women newly diagnosed with ABC recruited from six oncology units, 192
      completed an interview before their first course of chemotherapy (baseline) and
      follow-up interviews at 1.5, 3, 6, and 12 months thereafter. At baseline,
      participants were assessed for supportive care needs, psychological distress,
      physical symptom distress, optimism, and cancer-related rumination. At follow-up,
      participants completed the measure of psychological distress. Latent growth
      mixture modeling was used to identify trajectory patterns of distress.
      Multinominal logistic regression was used to identify predictors of trajectory
      patterns adjusted for demographic and medical characteristics. RESULTS: Four
      distinct trajectories of anxiety and depression were identified. Most women
      showed low-stable levels of anxiety (68%) and depression (68%), but one in 11
      women were chronically anxious (9%) and depressed (9%). Optimism, negative cancer
      related rumination, and physical symptom distress predicted both anxiety and
      depression trajectories. Psychological needs predicted anxiety trajectories.
      Women in the low-stable distress group reported high optimism, low psychological
      supportive care needs, low physical symptom distress, and low negative cancer
      related rumination. CONCLUSION: Most women with ABC did not experience
      psychological distress over 12 months following diagnosis of ABC. Preventive
      interventions should focus on women at risk of high persistent distress and
      reducing rumination, providing emotional support, and managing physical symptoms.

PMID- 24038546
TI  - Median nerve deformation and displacement in the carpal tunnel during finger
      motion.
AB  - The objective of this study was to evaluate the correlations between deformation
      and displacement of median nerve and flexor tendons during finger motion in the
      carpal tunnel for both carpal tunnel syndrome (CTS) patients and healthy
      controls. Sixty-two wrists of 31 asymptomatic volunteers and fifty-one wrists of
      28 idiopathic CTS patients were evaluated by ultrasound. The displacement of the
      median nerve and the middle finger flexor digitorum superficialis (FDS) tendon,
      as well as area, perimeter, aspect ratio of a minimum enclosing rectangle, and
      circularity of the median nerve were measured in finger extension and flexion
      positions. Deformation indices were defined as the ratios of indices in finger
      extension and flexion positions. The correlations between displacement and
      deformation indices were evaluated. There were significant correlations between
      nerve palmar-dorsal displacement and deformation indices (p < 0.05). The aspect
      ratio deformation index showed the strongest correlation to palmar-dorsal
      displacement of the nerve (-0.572, p < 0.01). This study showed that there is a
      relationship between median nerve deformation indices and nerve palmar-dorsal
      displacement in the carpal tunnel. Since the highest correlations were between
      palmar-dorsal nerve displacement direction and aspect ratio deformation index,
      these parameters may be helpful to understand the pathophysiology of CTS.

PMID- 24038547
TI  - A complete guide on the influence of metal clusters in the Diels-Alder
      regioselectivity of I(h)-C80 endohedral metallofullerenes.
AB  - The chemical functionalization of endohedral metallofullerenes (EMFs) has aroused
      considerable interest due to the possibility of synthesizing new species with
      potential applications in materials science and medicine. Experimental and
      theoretical studies on the reactivity of endohedral metallofullerenes are scarce.
      To improve our understanding of the endohedral metallofullerene reactivity, we
      have systematically studied with DFT methods the Diels-Alder cycloaddition
      between s-cis-1,3-butadiene and practically all X@I(h)-C80 EMFs synthesized to
      date: X=Sc3N, Lu3N, Y3N, La2, Y3, Sc3C2, Sc4C2, Sc3CH, Sc3NC, Sc4O2 and Sc4O3. We
      have studied both the thermodynamic and kinetic regioselectivity, taking into
      account the free rotation of the metallic cluster inside the fullerene. This
      systematic study has been made possible through the use of the frozen cage model
      (FCM), a computationally cheap approach to accurately predicting the exohedral
      regioselectivity of cycloaddition reactions in EMFs. Our results show that the
      EMFs are less reactive than the hollow I(h)-C80 cage. Except for the Y3 cluster,
      the additions occur predominantly at the [5,6] bond. In many cases, however, a
      mixture of the two possible regioisomers is predicted. In general, [6,6] addition
      is favored in EMFs that have a larger charge transfer from the metal cluster to
      the cage or a voluminous metal cluster inside. The present guide represents the
      first complete and exhaustive investigation of the reactivity of I(h)-C80-based
      EMFs.

PMID- 24038548
TI  - Studies on organophosphorus compounds. Part 1: synthesis and in vitro
      antimicrobial activity of some new pyrimido[5',4':5,6]pyrano[2,3
      d][1,3,2]thiazaphosphinine compounds.
AB  - 2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide (Lawesson's
      reagent, LR) reacted with pyrano[2,3-d]pyrimidine-2,4-(1H,3H)-dione derivatives
      in boiling acetonitrile to afford various pyrimido[5',4':5,6]pyrano[2,3
      d][1,3,2]thiazaphosphinine derivatives. The structures of the target compounds
      were characterized by elemental analysis and spectral data. The biological
      activities of all synthesized compounds were tested against various
      microorganisms by the disk diffusion method. In general, the newly synthesized
      compounds showed good inhibitory effects against most of the applied
      microorganisms. 

PMID- 24038549
TI  - Olfactory ensheathing cells promote corticospinal axonal outgrowth by a L1 CAM
      dependent mechanism.
AB  - Olfactory ensheathing cells (OECs) support the ability of the olfactory neuraxis
      to continually retarget within the mature central nervous system. This has led
      many groups to transplant OECS into the lesioned rodent spinal cord (SCd) in
      vivo, with variable degrees of anatomical, physiological, and behavioral success.
      Some of the most conflicting results in OEC transplantation have come from the
      corticospinal tract (CST) which has shown a relatively poor regeneration
      response. Although spinal neurite sprouting occurs in response to OECs in vivo
      and in vitro, we do not know if OECs possess the molecular machinery to stimulate
      outgrowth of functionally important motor tracts like the CST. Here, we assay
      cultured postnatal day 8 mouse CST neurons expressing yellow fluorescent protein
      (YFP) for their ability to extend axons and dendrites in response to different
      glia, and show that CST axons elongate in response to proteins in OEC plasma
      membrane (PM). In contrast, CST dendritic branching preferentially occurs in
      response to factors secreted by both OECs and astrocytes. We identify the L1
      neural cell adhesion molecule (L1-NCAM) as a major component of OEC-induced
      corticospinal axon elongation, and have determined that OEC PM factors (including
      L1), can stimulate CST outgrowth even when inhibition is induced by myelin
      associated glycoprotein. Together, these results suggest that in the right
      context, OEC-derived PM factors could enhance CST axonal regeneration, and
      potentially contribute to approaches to ameliorate recovery from SCd injury.

PMID- 24038551
TI  - CASP prediction center infrastructure and evaluation measures in CASP10 and CASP
      ROLL.
AB  - The Protein Structure Prediction Center at the University of California, Davis,
      supports the CASP experiments by identifying prediction targets, accepting
      predictions, performing standard evaluations, assisting independent CASP
      assessors, presenting and archiving results, and facilitating information
      exchange relating to CASP and structure prediction in general. We provide an
      overview of the CASP infrastructure implemented at the Center, and summarize
      standard measures used for evaluating predictions in the latest round of CASP.
      Several components were introduced or significantly redesigned for CASP10, in
      particular an improved assessors' common web-workspace; a Sphere Grinder
      visualization tool for analyzing local accuracy of predictions; brand new blocks
      for evaluation contact prediction and contact-assisted structure prediction;
      expanded evaluation and visualization tools for tertiary structure, refinement
      and quality assessment. Technical aspects of conducting the CASP10 and CASP ROLL
      experiments and relevant statistics are also provided.

PMID- 24038552
TI  - Amelioration of acidic soil increases the toxicity of the weak base carbendazim
      to the earthworm Eisenia fetida.
AB  - Ameliorating acidic soils is a common practice and may affect the bioavailability
      of an ionizable organic pollutant to organisms. The toxicity of the weak base
      carbendazim to the earthworm (Eisenia fetida) was studied in an acidic soil (pH
      H2O, 4.6) and in the ameliorated soil (pH-H2O, 7.5). The results indicated that
      the median lethal concentration of carbendazim for E. fetida decreased from 21.8
      mg/kg in acidic soil to 7.35 mg/kg in the ameliorated soil. To understand why the
      amelioration increased carbendazim toxicity to the earthworm, the authors
      measured the carbendazim concentrations in the soil porewater. The authors found
      increased carbendazim concentrations in porewater, resulting in increased
      toxicity of carbendazim to earthworms. The increased pore concentrations result
      from decreased adsorption because of the effects of pH and calcium ions.

PMID- 24038550
TI  - Selective accumulation of germ-line associated gene products in early development
      of the sea star and distinct differences from germ-line development in the sea
      urchin.
AB  - BACKGROUND: Echinodermata is a diverse phylum, a sister group to chordates, and
      contains diverse organisms that may be useful to understand varied mechanisms of
      germ-line specification. RESULTS: We tested 23 genes in development of the sea
      star Patiria miniata that fall into five categories: (1) Conserved germ-line
      factors; (2) Genes involved in the inductive mechanism of germ-line
      specification; (3) Germ-line associated genes; (4) Molecules involved in left
      right asymmetry; and (5) Genes involved in regulation and maintenance of the
      genome during early embryogenesis. Overall, our results support the contention
      that the posterior enterocoel is a source of the germ line in the sea star P.
      miniata. CONCLUSIONS: The germ line in this organism appears to be specified late
      in embryogenesis, and in a pattern more consistent with inductive interactions
      amongst cells. This is distinct from the mechanism seen in sea urchins, a close
      relative of the sea star clad. We propose that P. miniata may serve as a valuable
      model to study inductive mechanisms of germ-cell specification and when compared
      with germ-line formation in the sea urchin S. purpuratus may reveal developmental
      transitions that occur in the evolution of inherited and inductive mechanisms of
      germ-line specification.

PMID- 24038553
TI  - Stomal recurrence: salvage surgery and reconstruction utilizing microvascular
      free tissue transfer.
AB  - BACKGROUND: Stomal recurrence in patients after laryngectomy has a poor
      prognosis. Studies performed using sternal resection with pectoralis flap
      reconstruction report <25% 2-year survival. The purpose of this study was to
      ascertain whether the use of larger resection with free flap reconstruction
      improves survival. METHODS: Thirteen cases of stomal recurrence that underwent
      extended sternal resection and free flap reconstruction were identified and
      classified according to Sisson criteria. Postoperative morbidity, mortality, and
      survival were assessed. RESULTS: Median survival was 10 months in patients with
      Sisson types I and II, with 37.5% 1-year and 25% 2-year survival. Median survival
      was 6 months in patients with Sisson types III and IV, with 40% 1-year and 0% 2
      year survival. There were 2 perioperative deaths and a major morbidity rate of
      45%. CONCLUSION: Salvage surgery using free flap reconstruction did not show
      improved survival rates compared with previously described techniques.

PMID- 24038554
TI  - The ability of informal primary caregivers to accurately report cancer patients'
      difficulties.
AB  - BACKGROUND: In cancer care, informal primary caregivers provide healthcare
      professionals with key information regarding patient difficulties. The aim of
      this study was to assess their ability to report cancer patients' physical,
      psychological, and social difficulties. METHODS: We recruited 208 consecutive
      patients and their informal primary caregivers in 10 oncology units. Patients
      reported their difficulties on the CAncer Rehabilitation Evaluation System (CARES
      P), whereas caregivers reported their perception of patient difficulties on an
      adapted CARES questionnaire (CARES-C). On the basis of CARES-P and CARES-C
      questionnaire answers, correct report rates were defined by the percentage of
      difficulties reported at least 'a little' by patients and by caregivers. False
      report rates were defined by the percentage of difficulties not reported at least
      'a little' by patients and reported by caregivers. Patients and their caregivers
      also provided their distress levels (Hospital Anxiety and Depression Scale) and
      coping strategies. RESULTS: Caregivers correctly reported 67% of physical, 69% of
      psychological, and 40% of social difficulties experienced in patients. Caregivers
      falsely reported 28% of physical, 37% of psychological, and 22% of social
      difficulties not experienced by patients. Significant correlations were found
      between all correct and false reported rates. Patient and caregiver
      characteristics were weakly associated with caregivers' correct and false
      reports. CONCLUSIONS: Family primary caregivers correctly reported approximately
      two thirds of physical and psychological patients' difficulties; however, they
      had less accurate reports of patients' social difficulties. Correct report rates
      increased the probability of false report rates. Healthcare professionals should
      carefully evaluate the accuracy of a primary informal caregiver's report in
      regards to patient experiences.

PMID- 24038557
TI  - Is monitor flap monitoring?

PMID- 24038558
TI  - Kidney transplantation in atypical haemolytic uraemic syndrome (aHUS): a cheap
      way out?

PMID- 24038559
TI  - Living kidney transplantation in adult patients with atypical haemolytic uraemic
      syndrome.
AB  - BACKGROUND: Dysregulation of complement activation is the most common cause of
      the atypical haemolytic uraemic syndrome (aHUS). Many patients with aHUS develop
      end-stage renal disease and consider kidney transplantation. However, the
      recurrence rate after transplantation ranges from 45-90% in patients with known
      abnormalities in circulating complement proteins. It was recently proposed that
      patients with aHUS should be treated prophylactically with plasma exchange or
      eculizumab to prevent recurrence after transplantation. METHODS: A case series
      describing the successful outcome of kidney transplantation without prophylactic
      therapy in four adult patients with aHUS and a high risk of disease recurrence.
      Patients received a living donor kidney and immunosuppression consisting of
      basiliximab induction, low-dose tacrolimus, prednisone and mycophenolate mofetil.
      Patients received a statin, and were targeted to a low blood pressure preferably
      using blockers of the renin-angiotensin system. RESULTS: After a follow-up of 16
      21 months, none of the patients developed recurrent aHUS. Also, no rejection was
      observed. CONCLUSIONS: Kidney transplantation in adult patients with aHUS can be
      successful without prophylactic eculizumab, using a protocol that minimises cold
      ischaemia time, reduces the risk of rejection and provides endothelial
      protection. Our data suggest that in patients with aHUS, controlled trials are
      needed to demonstrate the optimal strategy.

PMID- 24038560
TI  - Cinacalcet for secondary hyperparathyroidism: from improved mineral levels to
      improved mortality?
AB  - Secondary hyperparathyroidism is an almost inevitable complication of advanced
      kidney failure. The introduction of the calcimimetic cinacalcet for the treatment
      of secondary hyperparathyroidism in patients on dialysis was based on its ability
      to reduce elevated levels of parathyroid hormone (PTH). Subsequent clinical
      studies confirmed the beneficial effects of cinacalcet on biochemical parameters
      reflecting mineral disturbances and bone disease. In this review we summarise the
      impact of cinacalcet on biochemical, intermediate and clinical outcomes. We also
      present previously unpublished mineral metabolism data from 144 Dutch dialysis
      patients treated with cinacalcet who participated in the pan-European ECHO
      observational study. Although secondary hyperparathyroidism tended to be more
      severe in our Dutch cohort, compared with the entire ECHO cohort, cinacalcet was
      nevertheless effective in reducing PTH in these patients. Two recent clinical
      studies evaluated, respectively, the efficacy of cinacalcet in improving the
      intermediate endpoint of cardiovascular calcifications (ADVANCE trial), and its
      impact on clinical outcomes, including all-cause mortality and cardiovascular
      events (EVOLVE trial). The ADVANCE trial provided evidence that cinacalcet may
      indeed improve calcification in both large arteries and cardiac valves. The
      EVOLVE trial, however, did not meet its clinical primary endpoint (time to all
      cause mortality, myocardial infarction, hospitalisation for unstable angina,
      heart failure or a peripheral vascular event), although secondary and sensitivity
      analysis suggested a beneficial effect. The clinical implications of these
      important studies are also addressed in this review. 

PMID- 24038561
TI  - No effect of atorvastatin and simvastatin on oxidative stress in patients at high
      risk for cardiovascular disease.
AB  - BACKGROUND: Statins are thought to have anti-atherogenic effects beyond
      cholesterol lowering. One such mechanism may involve reduction of oxidative
      stress. The aim of our study was to investigate and to compare the oxidative
      stress lowering capacity of atorvastatin with that of simvastatin in patients at
      high risk for cardiovascular disease using conventional markers and sensitive
      markers measured by highly specific techniques such as liquid chromatography
      tandem mass spectrometry. METHODS: We included 30 statin-naive patients with
      diabetes mellitus, and/or obesity, and/or hypertension (12 male, 18 female, mean
      age 44.8+/-11.1 years), and randomised them to receive either atorvastatin 10 mg
      or simvastatin 40 mg daily to obtain an equimolar cholesterol reduction. Blood
      and urine samples were obtained at baseline and at 1, 6 and 12 weeks. RESULTS:
      Low-density lipoprotein (LDL) cholesterol and coenzyme Q10 decreased
      significantly in both groups. Simvastatin caused a faster initial LDL cholesterol
      lowering than atorvastatin (p=0.01), but the overall effect after 12 weeks of
      atorvastatin and simvastatin was similar. Plasma myeloperoxidase and
      malondialdehyde did not change during the study period in the two groups. Urinary
      F2-isoprostanes decreased gradually and significantly in the atorvastatin group
      but not in the simvastatin group, but the between-group difference was not
      significant. Urinary 8-hydroxy-2-deoxyguanosine did not change in the two groups.

PMID- 24038562
TI  - Why you should ask your patients about their fishing hobbies.
AB  - Patients who use immunosuppressive agents, in particular medication that blocks
      tumour necrosis factor-a, are at risk for mycobacterial infections. Besides the
      typical Mycobacterium tuberculosis infection, a lso a typical mycobacterial
      disease may occur. Here we demonstrate two patients with such atypical
      mycobacterial infection due to swimming and fishing water contact. We propose
      that patients, before starting with immunosuppressive therapy, are counselled
      about risk factors for mycobacterial disease.

PMID- 24038563
TI  - A patient with a tumour in the breast and extensive haematomas. Scurvy.

PMID- 24038564
TI  - A patient with pure red cell aplasia after allogenic stem-cell transplantation.
      Parvo B19 infection.

PMID- 24038565
TI  - An accidental finding of multiple abdominal and pelvic tumours. Splenosis.

PMID- 24038566
TI  - Multiple spots on bone: diagnostic challenge or spot diagnosis? Osteopoikilosis.

PMID- 24038567
TI  - Treatment of hepatitis C monoinfection in adults--Dutch national guidelines.
AB  - In this new Dutch guideline for hepatitis C virus infection we provide
      recommendations for the management of hepatitis C infection. Until 2012 the
      standard for treatment consisted of pegylated interferon alpha (peg-IFNa) and
      ribavirin. The advent of first-generation direct antiviral agents such as
      boceprevir and telaprevir has changed the concept of treatment of adult chronic
      hepatitis C genotype 1 infected patients. There are three benefits of boceprevir
      and telaprevir. They increase the likelihood of cure in 1) naive genotype 1
      patients and 2) in patients who did not respond to earlier treatment with peg
      IFNa and ribavirin, while 3) allowing shortening of treatment duration from 48
      weeks to 24 or 28 weeks, which is possible in 40-60% of non-cirrhotic naive
      (boceprevir and telaprevir) and relapsing patients (telaprevir). The use of
      boceprevir and telaprevir is associated with multiple side effects and awareness
      of these side effects is needed to guide the patient through the treatment
      process. This guideline, formulated on behalf of The Netherlands Association of
      Hepato-gastroenterologists, The Netherlands Association of Internal Medicine, and
      The Dutch Association for the Study of Liver Disease, serves as a manual for
      physicians for the management and treatment of acute and chronic hepatitis C
      virus monoinfection in adults. 

PMID- 24038568
TI  - Vitamin B12 deficiency and the lack of its consequences in type 2 diabetes
      patients using metformin.
AB  - OBJECTIVES: To study vitamin B12 concentrations in patients with type 2 diabetes
      with and without metformin use and to identify risk factors and consequences of
      low vitamin B12 concentrations. RESEARCH DESIGN AND METHODS: This study had a
      cross-sectional design. During eight weeks all patients with type 2 diabetes
      visiting the diabetic outpatient clinic of the Isala Clinics in Zwolle were
      approached for participation. Participation included measurement of haemoglobin,
      mean corpuscular volume and vitamin B12 levels. Data on neuropathy were
      retrospectively searched for in the patient records. Vitamin B12 deficiency was
      defined as serum B12 concentrations <150 pmol/l. RESULTS: In the total cohort
      (n=298), the overall prevalence of vitamin B12 concentrations <150 pml/l was 9.7%
      (95% CI 6.6-13.7%). In type 2 diabetes patients not taking metformin (n=134), the
      prevalence was 4.4% (95% CI 1.6-9.4%) compared with 14.1% in metformin users
      (n=164) (95% CI 9.2-20.4%; p=0.006). Each 100 mg step in metformin dose increased
      (OR=1.081, p=0.014), whereas PPI use lowered (OR=0.322, p=0.037) the odds of
      having a vitamin B12 deficiency in logistic regression. Nevertheless, metformin
      use did not predict the chance on having anaemia or neuropathy. CONCLUSION: Among
      patients with type 2 diabetes using metformin, the prevalence of vitamin B12
      deficiency is higher than compared with patients not using metformin. However,
      metformin use did not predict the chance of having anaemia or neuropathy.

PMID- 24038569
TI  - Successful treatment after short course of telaprevir-based therapy in chronic
      hepatitis C infected patient.

PMID- 24038570
TI  - Effect of baseline cannabis use and working-memory network function on changes in
      cannabis use in heavy cannabis users: a prospective fMRI study.
AB  - Theoretical models of addiction suggest that a substance use disorder represents
      an imbalance between hypersensitive motivational processes and deficient
      regulatory executive functions. Working-memory (a central executive function) may
      be a powerful predictor of the course of drug use and drug-related problems. Goal
      of the current functional magnetic resonance imaging study was to assess the
      predictive power of working-memory network function for future cannabis use and
      cannabis-related problem severity in heavy cannabis users. Tensor independent
      component analysis was used to investigate differences in working-memory network
      function between 32 heavy cannabis users and 41 nonusing controls during an N
      back working-memory task. In addition, associations were examined between working
      memory network function and cannabis use and problem severity at baseline and at
      6-month follow-up. Behavioral performance and working-memory network function did
      not significantly differ between heavy cannabis users and controls. However,
      among heavy cannabis users, individual differences in working-memory network
      response had an independent effect on change in weekly cannabis use 6 months
      later (DeltaR(2) = 0.11, P = 0.006, f(2) = 0.37) beyond baseline cannabis use
      (DeltaR(2) = 0.41) and a behavioral measure of approach bias (DeltaR(2) = 0.18):
      a stronger network response during the N-back task was related to an increase in
      weekly cannabis use. These findings imply that heavy cannabis users requiring
      greater effort to accurately complete an N-back working-memory task have a higher
      probability of escalating cannabis use. Working-memory network function may be a
      biomarker for the prediction of course and treatment outcome in cannabis users.

PMID- 24038571
TI  - In-situ spin labeling of his-tagged proteins: distance measurements under in-cell
      conditions.
AB  - New spin labeling strategies have immense potential in studying protein structure
      and dynamics under physiological conditions with electron paramagnetic resonance
      (EPR) spectroscopy. Here, a new spin-labeled chemical recognition unit for
      switchable and concomitantly high affinity binding to His-tagged proteins was
      synthesized. In combination with an orthogonal site-directed spin label, this
      novel spin probe, Proxyl-trisNTA (P-trisNTA) allows the extraction of structural
      constraints within proteins and macromolecular complexes by EPR. By using the
      multisubunit maltose import system of E. coli: 1) the topology of the substrate
      binding protein, 2) its substrate-dependent conformational change, and 3) the
      formation of the membrane multiprotein complex can be extracted. Notably, the
      same distance information was retrieved both in vitro and in situ allowing for
      site-specific spin labeling in cell lysates under in-cell conditions. This
      approach will open new avenues towards in-cell EPR.

PMID- 24038572
TI  - Multifunctional nanoparticle@MOF core-shell nanostructures.
AB  - Controllable integration of inorganic nanoparticles (NPs) and metal-organic
      frameworks (MOFs) is leading to the creation of many new multifunctional
      materials. In this Research News, an emerging type of core-shell nanostructure,
      in which the inorganic NP cores are encapsulated by the MOF shells, is briefly
      introduced. Unique functions originating from the property synergies of different
      types of inorganic NP cores and MOF shells are highlighted, and insight into
      their future development is suggested. It is highly expected that this Research
      News could arouse research enthusiasm on such NP@MOF core-shell nanostructures,
      which have great application potential in devices, energy, the environment, and
      medicine. 

PMID- 24038573
TI  - Utilization of fentanyl buccal tablets in England: exploring off-label use
      reported in a cohort study.
AB  - BACKGROUND: Fentanyl citrate buccal tablets are indicated for the treatment of
      breakthrough pain (BTP) in cancer, in adults who are receiving maintenance opioid
      therapy for chronic cancer pain. OBJECTIVE: One of the objectives of this study
      was to describe the utilization characteristics of patients prescribed fentanyl
      buccal and to assess how the product is being used in relation to the terms of
      license of marketing approval. METHODS: An observational post-marketing cohort
      study was conducted. For the analysis of this study, exposure data were collected
      from dispensed prescriptions issued by general practitioners (GPs) between March
      2009 and June 2011. Outcome data (indication, event, patient demographic and
      selected clinical characteristics) were collected by sending questionnaires to
      GPs at least 6 months after the drug was first prescribed. Summary descriptive
      statistics were calculated. RESULTS: The cohort consisted of 551 patients, of
      which 54.8% (n = 302 patients) were female. The median age for the cohort was 62
      years (interquartile range: 50-72 years), with one patient (0.2%) aged less than
      18 years. A primary indication of BTP in cancer was reported for 61.9% (n = 341)
      patients. Regular opioid therapy was reported upon starting the treatment for 383
      patients (69.5% of cohort). In total, 69 patients (12.5%) had one or more
      contraindications for use. The most frequent initial titration dose was 100
      MUg/day (n = 247). CONCLUSIONS: The final study results show that fentanyl buccal
      is largely being prescribed according to the terms of the license in general
      practice in England, but off-licence use and use in the presence of
      contraindications and warnings have been reported.

PMID- 24038574
TI  - Reading group rehabilitation for patients with psychosis: a randomized controlled
      study.
AB  - OBJECTIVE: Group reading activities are often reported to be helpful in a variety
      of psychiatric conditions. However, data on the effects of structured reading
      rehabilitation activities, in both hospital and community settings for patients
      with psychosis, are still scarce. Our aim was to investigate the effects on
      clinical status, disability, psychosocial functioning and cognitive functioning
      of a structured group reading activity, in a sample of hospitalized patients with
      psychosis. METHODS: We enrolled 41 consecutive patients with psychosis and
      randomly assigned them to a structured group reading programme. For all included
      patients, we psychometrically evaluated clinical symptomatology, psychosocial
      functioning and disability, as well as cognitive functioning. All evaluations
      were repeated at a 6-month follow-up. Repeated-measure multiple analyses of
      variance were used to test the effect of the group reading activities on the
      clinical, psychosocial and cognitive measures. RESULTS: We found that, after 6
      months from discharge, structured group reading activities induced a
      statistically significant improvement of cognitive (p < 0.007) and psychosocial
      (p < 0.008) functioning in patients with psychosis and reduced their disability
      (p < 0.005), with respect to the control group. Furthermore, such programmes are
      easy to implement and were perceived as extremely 'interesting' and 'useful' by
      patients with psychosis. CONCLUSIONS: Rehabilitation programmes focusing on group
      reading activities should be regarded as a valid psychosocial rehabilitation tool
      for psychotic patients with severe mental disability. KEY PRACTITIONER MESSAGE: A
      structured group reading programme induced a significant symptomatological
      cognitive and psychosocial amelioration in hospitalized patients with psychosis.
      The improvement was sustained also at the 6-month follow-up, with respect to the
      control group. Structured group reading activities are perceived, by severely ill
      psychiatric patients, as highly useful, interesting and pleasant, while they are
      relatively easy to implement.

PMID- 24038575
TI  - Thermal stability of lysozyme as a function of ion concentration: a reappraisal
      of the relationship between the Hofmeister series and protein stability.
AB  - Anion and cation effects on the structural stability of lysozyme were
      investigated using differential scanning calorimetry. At low concentrations (<5
      mM) anions and cations alter the stability of lysozyme but they do not follow the
      Hofmeister (or inverse Hofmeister) series. At higher concentrations protein
      stabilization follows the well-established Hofmeister series. Our hypothesis is
      that there are three mechanisms at work. At low concentrations the anions
      interact with charged side chains where the presence of the ion can alter the
      structural stability of the protein. At higher concentrations the low charge
      density anions perchlorate and iodide interact weakly with the protein. Their
      presence however reduces the Gibbs free energy required to hydrate the core of
      the protein that is exposed during unfolding therefore destabilizing the
      structure. At higher concentrations the high charge density anions phosphate and
      sulfate compete for water with the protein as it unfolds increasing the Gibbs
      free energy required to hydrate the newly exposed core of the protein therefore
      stabilizing the structure. 

PMID- 24038576
TI  - Task force report: scales for screening and evaluating tremor: critique and
      recommendations.
AB  - The Movement Disorder Society established a task force to review rating scales
      for the assessment of tremor. Screening instruments used in identifying patients
      with tremor were also reviewed. Seven tremor severity scales, six activities of
      daily living (ADL)/disability scales, four quality-of-life scales, and five
      screening instruments were identified by searching PubMed.gov. The availability,
      use, acceptability, reliability, validity, and sensitivity to change were
      reviewed for each scale; and each scale was classified as recommended, suggested
      or listed based on whether 3, 2, or 1 of the following criteria were met: (1)
      used in the assessment of tremor (yes/no), (2) used in published studies by
      people other than the developers (yes/no), and (3) successful clinimetric testing
      (yes/no). Five tremor severity scales (the Fahn-Tolosa-Marin Tremor Rating Scale,
      the Bain and Findley Clinical Tremor Rating Scale, the Bain and Findley
      Spirography Scale, the Washington Heights-Inwood Genetic Study of Essential
      Tremor Rating Scale, and the Tremor Research Group Essential Tremor Rating
      Assessment Scale), one ADL/disability scale (the Bain and Findley Tremor ADL
      Scale), one quality-of-life scale (the Quality of Life in Essential Tremor
      Questionnaire), and one screening instrument (the Washington Heights-Inwood
      Genetic Study of Essential Tremor Rating Scale, version 1) are recommended using
      these criteria. However, all scales need a more comprehensive analysis of
      sensitivity to change in order to judge their utility in clinical trials and
      individual patient assessments. The task force recommends that further work with
      existing recommended scales be performed as opposed to the development of new
      tremor scales.

PMID- 24038577
TI  - Roles for HB-EGF and CD9 in multiple sclerosis.
AB  - Early events in multiple sclerosis (MS) lesion formation are loss of blood-brain
      barrier (BBB) integrity, immune cell trafficking into the central nervous system,
      and demyelination. To date, the molecular mechanisms underlying these pathogenic
      events are poorly understood. Heparin-binding epidermal growth factor (HB-EGF) is
      a trophic factor that is induced by inflammatory stimuli and has previously been
      shown to interact with tetraspanins (TSPs), a family of transmembrane proteins
      that are involved in cellular migration and adhesion. Given the known roles of
      TSPs and HB-EGF, we hypothesized that HB-EGF and TSPs may play a role in the
      processes that underlie MS lesion formation. We examined the expression of HB-EGF
      and the TSPs CD9 and CD81 in MS brain and found that HB-EGF was highly induced in
      reactive astrocytes in active lesions. TSPs were constitutively expressed
      throughout normal appearing white matter and control white matter. In contrast,
      CD9 was reduced in demyelinated lesions and increased on blood vessels in lesion
      areas. In vitro studies revealed that expression of HB-EGF and TSPs is regulated
      during inflammation. Importantly, blocking either HB-EGF or CD9 significantly
      reduced the migration of monocytes across brain endothelial cell monolayers.
      Moreover, blocking CD9 strongly enhanced the barrier function of the BBB in
      vitro. Together, we demonstrate that these molecules are likely implicated in
      processes that are highly relevant for MS lesion formation, and therefore, HB-EGF
      and TSPs are promising therapeutic targets.

PMID- 24038579
TI  - Organocatalyzed aldol reaction between pyridine-2-carbaldehydes and alpha
      ketoacids: a straightforward route towards indolizidines and isotetronic acids.
AB  - Enantioselective aldol reactions between substituted pyridine carbaldehydes and
      alpha-ketoacids were shown to provide isotetronic acids or their corresponding
      pyridinium salts, depending on the nature of the substituents on the pyridine
      ring. The pyridinium salts were generated through nucleophilic attack of the
      pyridine nitrogen atom onto the reactive keto functional group. Moderate-to-good
      yields of both compounds were typically obtained and high levels of
      enantioselectivity were observed by using benzimidazole pyrrolidine I as a
      catalyst. Hydrogenation of the resulting pyridinium salts led to new
      indolizidines with high ee values and diastereocontrol. X-ray diffraction studies
      allowed the determination of the relative configuration of the products. Finally,
      DFT calculations were performed to rationalize the divergent pathway as a
      function of the pyridine substituents. 

PMID- 24038578
TI  - Costimulation-adhesion blockade is superior to cyclosporine A and prednisone
      immunosuppressive therapy for preventing rejection of differentiated human
      embryonic stem cells following transplantation.
AB  - RATIONALE: Human embryonic stem cell (hESC) derivatives are attractive candidates
      for therapeutic use. The engraftment and survival of hESC derivatives as
      xenografts or allografts require effective immunosuppression to prevent immune
      cell infiltration and graft destruction. OBJECTIVE: To test the hypothesis that a
      short-course, dual-agent regimen of two costimulation-adhesion blockade agents
      can induce better engraftment of hESC derivatives compared to current
      immunosuppressive agents. METHODS AND RESULTS: We transduced hESCs with a double
      fusion reporter gene construct expressing firefly luciferase (Fluc) and enhanced
      green fluorescent protein, and differentiated these cells to endothelial cells
      (hESC-ECs). Reporter gene expression enabled longitudinal assessment of cell
      engraftment by bioluminescence imaging. Costimulation-adhesion therapy resulted
      in superior hESC-EC and mouse EC engraftment compared to cyclosporine therapy in
      a hind limb model. Costimulation-adhesion therapy also promoted robust hESC-EC
      and hESC-derived cardiomyocyte survival in an ischemic myocardial injury model.
      Improved hESC-EC engraftment had a cardioprotective effect after myocardial
      injury, as assessed by magnetic resonance imaging. Mechanistically, costimulation
      adhesion therapy is associated with systemic and intragraft upregulation of T
      cell immunoglobulin and mucin domain 3 (TIM3) and a reduced proinflammatory
      cytokine profile. CONCLUSIONS: Costimulation-adhesion therapy is a superior
      alternative to current clinical immunosuppressive strategies for preventing the
      post-transplant rejection of hESC derivatives. By extending the window for
      cellular engraftment, costimulation-adhesion therapy enhances functional
      preservation following ischemic injury. This regimen may function through a TIM3
      dependent mechanism.

PMID- 24038580
TI  - Trophic stimulation of articular chondrocytes by late-passage mesenchymal stem
      cells in coculture.
AB  - Coculture of mesenchymal stem cells (MSCs) with articular chondrocytes (ACs)
      increases glycosaminoglycan (GAG) accumulation compared to monoculture. MSCs
      might (1) differentiate into ACs (progenitor role) and/or (2) stimulate AC matrix
      metabolism (trophic role). MSCs lose the ability to undergo chondrogenesis after
      extended passaging. We hypothesized that MSCs act predominantly as progenitors,
      and that late-passage MSCs without chondrogenic potential would be unable to
      increase GAG in coculture. Early- and late-passage human MSCs (hMSCs) were grown
      in pellet monoculture under chondrogenic conditions and in pellet coculture with
      bovine ACs. Chondrogenesis was assessed with GAG quantification, safranin-O
      staining, and quantitative PCR (qPCR). Contributions of human and bovine cells
      were assessed with species-specific qPCR and human-specific immunostaining. Late
      passage hMSCs did not undergo chondrogenesis in monoculture with chondrogenic
      stimuli or in coculture with ACs. Early-passage hMSCs underwent chondrogenesis
      only in response to chondrogenic stimuli. Coculture pellets in both cases
      accumulated as much GAG/DNA as monoculture AC pellets. Aggrecan transcription was
      not increased in coculture. Late-passage hMSCs that do not undergo chondrogenesis
      are capable of stimulating GAG accumulation in coculture with ACs. This supports
      a trophic effect of hMSCs on ACs. hMSCs may have therapeutic utility even after
      prolonged passaging.

PMID- 24038581
TI  - The novel, actin-like protein Tact3 is expressed in rodent testicular haploid
      germ cells.
AB  - Mouse testis actin-like proteins 1 and 2 (mTact1 and mTact2), which are expressed
      in murine haploid germ cells, have been described previously. Here, we report the
      cloning and characterization of a third actin-like protein from rat, rat testis
      actin-like protein 3 (rTact3). The complete cDNA of the rTact3 gene was
      approximately 3.7 kb in length, and its corresponding amino acid sequence
      consisted of 1219 amino acids. The rTact3 gene lacks introns, similar to mTact1
      and mTact2. The 356 C-terminal amino acids of rTact3 showed 43% homology with
      mTact1, whereas the 863 N-terminal amino acids did not show any significant
      homology. Northern blot analysis revealed that rTact3 mRNA was expressed only in
      adult rat testes and not during the prepubescent stage. In situ hybridization
      revealed that rTact3 was expressed exclusively during round and elongated
      spermatids maturation stages in rat testes. Immunohistochemical experiments using
      antibodies raised against a synthetic peptide showed that the expression of the
      rTact3 protein was also restricted in round and elongated spermatids,
      specifically in the head and acrosome of mature rat sperm. The 5'-flanking region
      of the mTact3 gene was found to contain a TATA-box motif as well as two putative
      CREB/c-Jun and five C/EBP motifs. mTact3 promoter activity was enhanced in a dose
      dependent manner by the transfection of CREB, c-Jun, or C/EBP in NIH3T3 cells.
      These results suggest that Tact3 proteins might play an important role in rodent
      germ-cell development.

PMID- 24038582
TI  - rbm47, a novel RNA binding protein, regulates zebrafish head development.
AB  - BACKGROUND: Vertebrate trunk induction requires inhibition of bone morphogenetic
      protein (BMP) signaling, whereas vertebrate head induction requires concerted
      inhibition of both Wnt and BMP signaling. RNA binding proteins play diverse roles
      in embryonic development and their roles in vertebrate head development remain to
      be elucidated. RESULTS: We first characterized the human RBM47 as an RNA binding
      protein that specifically binds RNA but not single-stranded DNA. Next, we knocked
      down rbm47 gene function in zebrafish using morpholinos targeting the start codon
      and exon-1/intron-1 splice junction. Down-regulation of rbm47 resulted in
      headless and small head phenotypes, which can be rescued by a wnt8a blocking
      morpholino. To further reveal the mechanism of rbm47's role in head development,
      microarrays were performed to screen genes differentially expressed in normal and
      knockdown embryos. epcam and a2ml were identified as the most significantly up-
      and down-regulated genes, respectively. The microarrays also confirmed up
      regulation of several genes involved in head development, including gsk3a, otx2,
      and chordin, which are important regulators of Wnt signaling. CONCLUSIONS:
      Altogether, our findings reveal that Rbm47 is a novel RNA-binding protein
      critical for head formation and embryonic patterning during zebrafish
      embryogenesis which may act through a Wnt8a signaling pathway.

PMID- 24038583
TI  - Understanding bioavailability and toxicity of sediment-associated contaminants by
      combining passive sampling with in vitro bioassays in an urban river catchment.
AB  - Bioavailable and bioaccessible fractions of sediment-associated contaminants are
      considered as better dose metrics for sediment-quality assessment than total
      concentrations. The authors applied exhaustive solvent extraction and
      nondepletive equilibrium sampling techniques to sediment samples collected along
      the Brisbane River in South East Queensland, Australia, which range from pristine
      environments to urban and industry-impacted areas. The wide range of chemicals
      expected prevents comprehensive chemical analysis, but a battery of cell-based
      bioassays sheds light on mixture effects of chemicals in relation to various
      modes of toxic action. Toxic effects were expressed as bioanalytical equivalent
      concentrations (BEQs) normalized to the organic carbon content of each sediment
      sample. Bioanalytical equivalent concentrations from exhaustive extraction agreed
      fairly well with values estimated from polydimethylsiloxane passive sampling
      extracts via the constant organic carbon to polydimethylsiloxane partition
      coefficient. Agreement was best for bioassays indicative of photosynthesis
      inhibition and oxidative stress response and discrepancy within a factor of 3 for
      the induction of the aryl hydrocarbon receptor. For nonspecific cytotoxicity, BEQ
      from exhaustive extraction were 1 order of magnitude higher than values from
      equilibrium sampling, possibly because of coextraction of bioactive natural
      organic matter that led to an overestimation of toxicity in the exhaustive
      extracts, which suggests that passive sampling is better suited in combination
      with bioanalytical assessment than exhaustive extraction.

PMID- 24038584
TI  - Evolutionary relationship between 5+5 and 7+7 inverted repeat folds within the
      amino acid-polyamine-organocation superfamily.
AB  - Evidence has been presented that 5+5 TMS and 7+7 TMS inverted repeat fold
      transporters are members of a single superfamily named the Amino acid-Polyamine
      organoCation (APC) superfamily. However, the evolutionary relationship between
      the 5+5 and the 7+7 topological types has not been established. We have
      identified a common fold, consisting of a spiny membrane helix/sheet, followed by
      a U-like structure and a V-like structure that is recurrent between domain
      duplicated units of 5+5 and 7+7 inverted repeat folds. This fold is found in the
      following protein structures: AdiC, ApcT, LeuT, Mhp1, BetP, CaiT, and SglT (all
      5+5 TMS repeats), as well as UraA and SulP (7+7 TMS repeats). AdiC, LeuT and Mhp1
      have two extra TMSs after the second duplicated domain, SglT has four extra C
      terminal TMSs, and BetP has two extra TMSs before the first duplicated domain.
      UraA and SulP on the other hand have two extra TMSs at the N-terminus of each
      duplicated domain unit. These observations imply that multiple hairpin and domain
      duplication events occurred during the evolution of the APC superfamily. We
      suggest that the five TMS architecture was primordial and that families gained
      two TMSs on either side of this basic structure via dissimilar hairpin
      duplications either before or after intragenic duplication. Evidence for homology
      between TMSs 1-2 of AdiC and TMSs 1-2 and 3-4 of UraA suggests that the 7+7
      topology arose via an internal duplication of the N-terminal hairpin loop within
      the five TMS repeat unit followed by duplication of the 7 TMS domain.

PMID- 24038585
TI  - Lymph node distribution in the central compartment of the neck: an anatomic
      study.
AB  - BACKGROUND: Dissection of the central compartment of the neck (CCN) is performed
      for proven or suspected lymph node metastases of thyroid carcinoma. During this
      procedure, the recurrent laryngeal nerves and the parathyroid glands are at risk.
      The purpose of this study was to determine the anatomic distribution of the lymph
      nodes in the CCN. METHODS: The anatomic distribution of the lymph nodes in the
      CCN was studied by dissection of 30 fresh cadavers. The soft tissue between the
      cricoid cartilage and the innominate vein, carotid arteries, and prevertebral
      fascia was removed and divided according to CCN sublevels. Nodules were
      identified by palpation in the specimen and sent for pathological examination.
      RESULTS: Three to 44 (18.5 +/- 10.29) nodules were identified macroscopically.
      Two to 42 nodules were confirmed as lymph nodes after microscopic examination.
      The lymph node distribution was as follows: precricoid: 0 to 2 (0.9 +/- 0.72);
      pretracheal: 1 of 35 (12.4 +/- 8.19); lateral to the right recurrent laryngeal
      nerve (RLN): 0 to 11 (3.4 +/- 2.34); and lateral to the left: 0 to 4 (1.7 +/-
      1.30). Twenty-six parathyroid glands were removed by 14 dissections. The
      innominate vein was found at 15 mm above the superior border of the clavicles to
      35 mm below on the left side of the neck and 5 to 45 mm on the right side.
      CONCLUSION: The number of confirmed lymph nodes in the central neck varied from 2
      to 42. Sixty-seven percent of the lymph nodes were in the pretracheal sublevel.
      There was no division between level VI and VII lymph nodes. Additionally, the
      innominate vein was found to be from 15 mm above the superior border of the
      clavicles to 35 mm below on the left side of the neck and 5 to 45 mm on the right
      side. Parathyroid glands were identified to be far away from the thyroid gland.

PMID- 24038586
TI  - Single versus dual venous anastomoses of the free fibula osteocutaneous flap in
      mandibular reconstruction: a retrospective study.
AB  - OBJECTIVE: The present study was to compare the success rates of single venous
      anastomosis with dual venous anastomoses of the free fibula osteocutaneous flap
      in mandibular reconstruction. PATIENTS AND METHODS: Retrospective review of all
      cases of mandibular reconstruction using free fibula osteocutaneous flaps
      performed by a single surgeon in our department during the period January 2005 to
      April 2012. All the flaps were harvested and transplanted by the standard
      protocols. Microvascular anastomosis of either one or two veins was performed. In
      addition to routine clinical evaluation, the viability of the flap was evaluated
      by a portable Doppler at the tenth day after surgery. RESULTS: Two hundred and
      one free fibula osteocutaneous flaps were performed during this time period.
      Single venous anastomosis was performed in 112 flaps and dual venous anastomoses
      were performed in 89 flaps. The overall incidence of vascular thrombosis was 3%,
      and the success rate of the transplantation was 98.5%. Six cases developed
      vascular thrombosis postoperatively. One was arterial thrombosis that occurred 12
      hours after initial operation in the dual venous anastomoses group. Three venous
      thrombosis occurred 24 hr after the operation in the single venous anastomosis
      group. In dual venous anastomoses group, two venous thrombosis occurred 3-4 days
      after initial operation and attempt to salvage failed in both the cases. Fisher's
      exact test showed that there was no significant difference of the success rate
      between single and dual anastomoses groups (P = 0.59). CONCLUSIONS: There is no
      difference in success rates between single venous anastomosis and dual venous
      anastomoses for mandibular reconstruction with free fibula osteocutaneous flap.

PMID- 24038587
TI  - Dopamine-agonists and impulsivity in Parkinson's disease: impulsive choices vs.
      impulsive actions.
AB  - The control of impulse behavior is a multidimensional concept subdivided into
      separate subcomponents, which are thought to represent different underlying
      mechanisms due to either disinhibitory processes or poor decision-making. In
      patients with Parkinson's disease (PD), dopamine-agonist (DA) therapy has been
      associated with increased impulsive behavior. However, the relationship among
      these different components in the disease and the role of DA is not well
      understood. In this imaging study, we investigated in PD patients the effects of
      DA medication on patterns of brain activation during tasks testing impulsive
      choices and actions. Following overnight withdrawal of antiparkinsonian
      medication, PD patients were studied with a H2 ((15)) O PET before and after
      administration of DA (1 mg of pramipexole), while they were performing the delay
      discounting task (DDT) and the GoNoGo Task (GNG). We observed that pramipexole
      augmented impulsivity during DDT, depending on reward magnitude and activated the
      medial prefrontal cortex and posterior cingulate cortex and deactivated ventral
      striatum. In contrast, the effect of pramipexole during the GNG task was not
      significant on behavioral performance and involved different areas (i.e., lateral
      prefrontal cortex). A voxel-based correlation analysis revealed a significant
      negative correlation between the discounting value (k) and the activation of
      medial prefrontal cortex and posterior cingulate suggesting that more impulsive
      patients had less activation in those cortical areas. Here we report how these
      different subcomponents of inhibition/impulsivity are differentially sensitive to
      DA treatment with pramipexole influencing mainly the neural network underlying
      impulsive choices but not impulsive action.

PMID- 24038588
TI  - Quercetin and EGCG exhibit chemopreventive effects in cholangiocarcinoma cells
      via suppression of JAK/STAT signaling pathway.
AB  - Quercetin and epigallocatechin-3-gallate (EGCG) are dietary phytochemicals with
      antiinflammatory and antitumor effects. In the present study, we examined the
      effects of these two compounds on Janus-like kinase (JAK)/signal transduction and
      transcription (STAT) pathway of cholangiocarcinoma (CCA) cells, because CCA is
      one of the aggressive cancers with very poor prognosis and JAK/STAT pathway is
      critically important in inflammation and carcinogenesis. The results showed that
      the JAK/STAT pathway activation by proinflammatory cytokine interleukin-6 and
      interferon-gamma in CCA cells was suppressed by pretreatment with quercetin and
      EGCG, evidently by a decrease of the elevated phosphorylated-STAT1 and STAT3
      proteins in a dose-dependent manner. The cytokine-mediated up-regulation of
      inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1
      (ICAM-1) via JAK/STAT cascade was abolished by both quercetin and EGCG
      pretreatment. Moreover, these flavonoids also could inhibit growth and cytokine
      induced migration of CCA cells. Pretreatment with specific JAK inhibitors, AG490
      and piceatannol, abolished cytokine-induced iNOS and ICAM-1 expression. These
      results demonstrate beneficial effects of quercetin and EGCG in the suppression
      of JAK/STAT cascade of CCA cells. Quercetin and EGCG would be potentially useful
      as cancer chemopreventive agents against CCA.

PMID- 24038589
TI  - Systematic administration of B vitamins attenuates neuropathic hyperalgesia and
      reduces spinal neuron injury following temporary spinal cord ischaemia in rats.
AB  - BACKGROUND: B vitamins have been demonstrated to be effective in treating chronic
      pain due to peripheral nerve injury. We investigated whether B vitamins could
      alleviate neuropathic pain and reduce neuron injury following temporary ischaemia
      in a rat model of spinal cord ischaemia-reperfusion injury (SCII). METHODS: SCII
      was produced by transiently blocking the unilateral lumbar arteries in adult male
      Sprague-Dawley rats. Behavioural and neurochemical signs of neuropathic pain and
      spinal neuron injury were analysed with and without B vitamin treatment. RESULTS:
      SCII caused behavioural thermal hyperalgesia and mechanical allodynia and
      neurochemical alterations, including increased expression of the vanilloid
      receptor 1 (VR1) and induction of c-Fos, as well as activation of the astrocytes
      and microglial cells in the spinal cord. Repetitive systemic administration of
      vitamin B complex (B1/B6/B12 at 33/33/0.5 mg/kg, i.p., daily, for 7-14
      consecutive days) significantly reduced thermal hyperalgesia and the increased
      expression of VR1 and c-Fos, as well as activation of the astrocytes and
      microglial cells. SCII caused a dramatic decrease of the expression of the rate
      limiting enzyme glutamic acid decarboxylase-65 (GAD65), which synthesizes gamma
      aminobutyric acid (GABA) in the axonal terminals, and beta-III-tubulin, and also
      caused loss of Nissl bodies in the spinal cord. These alterations were largely
      prevented and rescued by the B vitamin treatment. CONCLUSIONS: These findings
      support the idea that the B vitamins are capable of neuroprotection and
      antinociception during spinal cord injury due to temporary ischaemia. Rescuing
      the loss of inhibitory GABAergic tone may reduce spinal central sensitization and
      contribute to B vitamin-induced analgesia.

PMID- 24038590
TI  - Young childless women with breast cancer in the UK: a qualitative study of their
      fertility-related experiences, options, and the information given by health
      professionals.
AB  - OBJECTIVE: A proportion of young women diagnosed with breast cancer are
      childless. Fertility can be impaired by treatment, and women may have to wait for
      a number of years before pregnancy is advised. The aim of this qualitative study
      was to investigate in detail the fertility-related experiences of young childless
      women with breast cancer, including the information they received, the fertility
      preservation options given, and the dilemmas they faced. METHOD: Interviews were
      conducted with 19 childless women aged below 45 with first episode breast cancer
      diagnosed at least 6 months before. They were recruited by contacting the breast
      cancer charities and were asked to tell their story, with an emphasis on
      fertility issues. Transcripts were analyzed using the thematic method developed
      by Braun and Clarke. RESULTS: The amount of information given to women from
      health professionals varied considerably. Only half were given the opportunity to
      pursue assisted reproductive techniques prior to chemotherapy. Most women were
      worried about what the future might hold, including their fertility, the impact
      of pregnancy on recurrence, and the health of the child. They were generally
      given little information or support on these issues. CONCLUSIONS: Young women
      should be given more detailed information about fertility issues shortly after
      diagnosis, after chemotherapy, and during follow-up appointments. More holistic
      care should include emotional support to enable them to make decisions regarding
      their fertility options and planning for the future.

PMID- 24038591
TI  - Acenaphthylene-fused cyclo[8]pyrroles with intense near-IR-region absorption
      bands.
AB  - An acenaphthylene-fused cyclo[8]pyrrole was synthesized by using an oxidative
      coupling reaction of the corresponding 2,2'-bipyrrole. Two conformational isomers
      1 a and 1 b were isolated, and their molecular structures were elucidated by X
      ray crystallographic studies. The less-polar and lower-symmetry 1 b isomer can be
      converted into the 1 a isomer through a thermal ring flip. Application of the
      perimeter model developed by Michl to magnetic circular dichroism spectroscopic
      data and theoretical calculations demonstrate that there is a marked redshift of
      the near-IR absorption maxima relative to cyclo[8]isoindole because there is a
      significant stabilization of the LUMO due to the differing effects of a fused
      ring expansion with acenaphthylene and benzene moieties on the frontier pi
      molecular orbitals. 

PMID- 24038592
TI  - Concise review: hurdles in a successful example of limbal stem cell-based
      regenerative medicine.
AB  - Recent breakthroughs in regenerative medicine have generated enthusiasm and many
      efforts to explore new therapeutic potentials of both somatic and pluripotent
      stem cells. About 30 years passed since a discovery of a method of producing a
      great number of human epidermal keratinocytes by cultivation from a small skin
      biopsy, many possibilities are now envisaged for therapeutic application of
      different cultured cell types. The importance of stem cell content was proven for
      many tissues or organs in different pathologies. Ocular burns cause depletion of
      limbal stem cells, which lead to corneal opacification and visual loss. Most of
      available treatments are palliative and focused on the relief of the devastating
      clinical picture. This review is focused on recent developments in cell-based
      therapy of limbal stem cell deficiency. All findings can provide support for
      improvement and standardization of the cure for this disabling disease.

PMID- 24038593
TI  - Relation of clinical subtypes in Parkinson's disease with survival.

PMID- 24038594
TI  - Roles of parathyroid hormone (PTH) receptor and reactive oxygen species in
      hyperlipidemia-induced PTH resistance in preosteoblasts.
AB  - Bioactive lipids initiate inflammatory reactions leading to pathogenesis of
      atherosclerosis. Evidence shows that they also contribute to bone loss by
      inhibiting parathyroid hormone receptor (PTH1R) expression and differentiation of
      osteoblasts. We previously demonstrated that bone anabolic effects of PTH(1-34)
      are blunted in hyperlipidemic mice and that these PTH effects are restored by
      antioxidants. However, it is not clear which osteoblastic cell developmental
      stage is targeted by bioactive lipids. To investigate the effects of
      hyperlipidemia at the cellular level, hyperlipidemic Ldlr(-/-) mice were bred
      with Col3.6GFPtpz mice, in which preosteoblasts/osteoblasts carry a topaz
      fluorescent label, and with Col2.3GFPcyan mice, in which more mature
      osteoblasts/osteocytes carry a cyan fluorescent label. Histological analyses of
      trabecular bone surfaces in femoral as well as calvarial bones showed that
      intermittent PTH(1-34) increased fluorescence intensity in WT-Tpz mice, but not
      in Tpz-Ldlr(-/-) mice. In contrast, PTH(1-34) did not alter fluorescence
      intensity in femoral cortical envelopes of either WT-Cyan or Ldlr(-/-)-Cyan mice.
      To test the mechanism of PTH1R downregulation, preosteoblastic MC3T3-E1 cells
      were treated with bioactive lipids and the antioxidant Trolox. Results showed
      that inhibitory effects of PTH1R levels by bioactive lipids were rescued by
      pretreatment with Trolox. The inhibitory effects on expression of PTH1R as well
      as on PTH-induced osteoblastic genes were mimicked by xanthine/xanthine oxidase,
      a known generator of reactive oxygen species. These findings suggest an important
      role of the preosteoblastic development stage as the target and downregulation of
      PTH receptor expression mediated by intracellular oxidant stress as a mechanism
      in hyperlipidemia-induced PTH resistance.

PMID- 24038596
TI  - High-performance nanowire oxide photo-thin film transistor.
AB  - A gate-modulated nanowire oxide photosensor is fabricated by electron-beam
      lithography and conventional dry etch processing.. The device characteristics are
      good, including endurance of up to 10(6) test cycles, and gate-pulse excitation
      is used to remove persistent photoconductivity. The viability of nanowire oxide
      phototransistors for high speed and high resolution applications is demonstrated,
      thus potentially expanding the scope of exploitation of touch-free interactive
      displays. 

PMID- 24038595
TI  - Identifying newly approved medications in Medicare claims data: a case study
      using tocilizumab.
AB  - BACKGROUND: After U.S. licensure, parenterally administered medications are
      identified using non-specific drug codes. Accurately identifying these
      medications is critical to safety and effectiveness research. Methods to identify
      medications prior to assignment of specific drug codes have not been well
      described. OBJECTIVES: To describe a generalized approach using non-specific drug
      codes to identify parenteral therapies in Medicare claims and to assess the
      ability of that approach to identify tocilizumab (TCZ), a new biologic agent
      approved in 2010. METHODS: We used 2008-2010 Medicare data for a cohort of
      rheumatoid arthritis patients for algorithm development. Our algorithm classified
      non-specific drug codes based upon: 1) ICD9 codes; 2) unit values (i.e. dose); 3)
      codes for infusion/injection procedures; 4) expected versus observed total
      reimbursement amount and reimbursement per unit. We assessed algorithm
      performance by linking to an arthritis registry to examine external validity.
      RESULTS: Of 472 803 claims with non-specific drug codes, 9762 claims satisfied
      the TCZ algorithm. 74.3% of 9762 claims were classified as TCZ by exact unit
      price or allowed amount, 4.4% by unique doses, 21.3% by diagnosis code and small
      deviation from unit price or allowed amount. The algorithm demonstrated good
      performance characteristics: sensitivity 94% (95% CI 80-99), specificity 100% (99
      100) and PPV 97% (84-100). CONCLUSION: Claims-based algorithms in Medicare or
      similar data systems can accurately identify newly approved biologics
      administered parenterally prior to the assignment of specific drug codes.

PMID- 24038597
TI  - Theory of sliding-mode triboelectric nanogenerators.
AB  - The triboelectric nanogenerator (TENG) is a powerful approach toward new energy
      technology, especially for portable electronics. A theoretical model for the
      sliding-mode TENG is presented in this work. The finite element method was
      utilized to characterize the distributions of electric potential, electric field,
      and charges on the metal electrodes of the TENG. Based on the FEM calculation,
      the semi-analytical results from the interpolation method and the analytical V-Q
      x relationship are built to study the sliding-mode TENG. The analytical V-Q-x
      equation is validated through comparison with the semi-analytical results.
      Furthermore, based on the analytical V-Q-x equation, dynamic output performance
      of sliding-mode TENG is calculated with arbitrary load resistance, and good
      agreement with experimental data is achieved. The theory presented here is a
      milestone work for in-depth understanding of the working mechanism of the sliding
      mode TENG, and provides a theoretical basis for further enhancement of the
      sliding-mode TENG for both energy scavenging and self-powered sensor
      applications. 

PMID- 24038598
TI  - Reactivity of bridged pentelidene complexes with isonitriles: a new way to pentel
      containing heterocycles.
AB  - The reaction of [Cp*E{W(CO)5 }2 ] (E=P (1 a), As (1 b); Cp*=1,2,3,4,5
      pentamethylcyclopentadienyl) with isonitriles RNC (R=tBu, cyclohexyl (Cy), nBu)
      depends on the steric demand of the substituent at the isonitrile as well as on
      the stoichiometry of the starting materials. With tBuNC only the Lewis acid/base
      adducts [Cp*E{W(CO)5 }2 (CNtBu)] (E=P (2 a), As (2 b)) are formed. The use of Cy
      and n-butylisonitrile leads first to the formation of the Lewis acid/base adduct,
      but only at low temperatures. At ambient temperatures, a rearrangement occurs and
      bicyclo[3.2.0]heptane derivatives of the type [{C(Me)C(CH2 )C(Me)C(Me)C(Me)}C(NR)
      E{W(CO)5 }2 ] (E=P, As; R=Cy, nBu) (3 a-Cy, 3 b-Cy, 3 a-nBu and 3 b-nBu) are
      obtained. The use of a further equivalent of isonitrile results in products
      revealing two new structural motifs, the four-membered ring derivatives
      [C(Cp*)N(R)C(NR)E{W(CO)5 }2 ] (4: E=P, As; R=Cy, nBu) and the bicyclic complexes
      [[{C(Me)C- (CH2 )C(Me)C(Me)C(Me)}C(NR)2 - E{W(CO)5 }2 ] (5: E=As; R=Cy). The
      reaction pathway depends on the substituent at the isonitrile. By treatment of 1
      a with two equivalents of CyNC only a 2H-1,3-azaphosphet complex 4 a-Cy (E=P;
      R=Cy) is formed. Treatment of 1 b with two equivalents of CyNC exclusively leads
      to the complex 5 b-Cy (E=As; R=Cy). Treatment of 1 a with two equivalents of
      nBuNC results in a mixture of complexes, the 2H-1,3-azaphosphet 4 a-nBu (E=P;
      R=nBu) and the bicyclic complex 5 a-nBu (E=P; R=nBu). For the arsenidene complex
      1 b a mixture of the 2H-1,3-azarsete complex 4 b-nBu (E=As; R=nBu) and the
      bicyclic complex 5 b-nBu (E=P, As; R=Cy, nBu) is obtained. Complex 4 b-nBu is the
      first example of a 2H-1,3-azarsete complex. All products have been characterized
      by using mass spectrometry, NMR spectroscopy, and X-ray diffraction analysis.

PMID- 24038599
TI  - Complement protein C3 exacerbates prion disease in a mouse model of chronic
      wasting disease.
AB  - Accumulating evidence shows a critical role of the complement system in
      facilitating attachment of prions to both B cells and follicular dendritic cells
      and assisting in prion replication. Complement activation intensifies disease in
      prion-infected animals, and elimination of complement components inhibits prion
      accumulation, replication and pathogenesis. Chronic wasting disease (CWD) is a
      highly infectious prion disease of captive and free-ranging cervid populations
      that utilizes the complement system for efficient peripheral prion replication
      and most likely efficient horizontal transmission. Here we show that complete
      genetic or transient pharmacological depletion of C3 prolongs incubation times
      and significantly delays splenic accumulation in a CWD transgenic mouse model.
      Using a semi-quantitative prion amplification scoring system we show that C3
      impacts disease progression in the early stages of disease by slowing the rate of
      prion accumulation and/or replication. The delayed kinetics in prion replication
      correlate with delayed disease kinetics in mice deficient in C3. Taken together,
      these data support a critical role of C3 in peripheral CWD prion pathogenesis.

PMID- 24038600
TI  - Human skin-derived keratinocytes and fibroblasts co-cultured on 3D poly epsilon
      caprolactone scaffold support in vitro HSC differentiation into T-lineage
      committed cells.
AB  - In humans, the thymus is the primary lymphoid organ able to support the
      development of T cells through its three-dimensional (3D) organization of the
      thymic stromal cells. Since a remarkable number of similarities are shared
      between the thymic epithelial cells (TECs) and skin-derived keratinocytes and
      fibroblasts, in this study we used human keratinocytes seeded with fibroblasts on
      the 3D poly epsilon-caprolactone scaffold to evaluate their ability to replace
      TECs in supporting T-cell differentiation from human haematopoietic stem cells
      (HSCs). We observed that in the multicellular biocomposite, early thymocytes
      expressing CD7(+)CD1a(+), peculiar markers of an initial T-cell commitment, were
      de novo generated. Molecular studies of genes selectively expressed during T-cell
      development revealed that TAL1 was down-regulated and Spi-B was up-regulated in
      the cell suspension, consistently with a T-cell lineage commitment. Moreover,
      PTCRA and RAG2 expression was detected, indicative of a recombinant activity,
      required for the generation of a T-cell receptor repertoire. Our results indicate
      that in the multicellular biocomposite, containing skin-derived elements in the
      absence of thymic stroma, HSCs do start differentiating toward a T-cell lineage
      commitment. In conclusion, the construct described in this study exerts some
      properties of a lymphoid organoid, suitable for future clinical applications in
      cell-based therapies.

PMID- 24038601
TI  - Biased usage and preferred pairing of alpha- and beta-chains of TCRs specific for
      an immunodominant gluten epitope in coeliac disease.
AB  - CD4+ T cells that recognize dietary gluten antigens presented by the disease
      associated HLA-DQ2 or DQ8 molecules are central players in coeliac disease.
      Unbiased sequencing of the human TCRalpha variable (TRAV) and humanTCRbeta
      variable (TRBV) genes of 68 HLA-DQ2.5-glia-alpha2-specific T cells from coeliac
      disease patients confirmed previous reports of over-usage of the TRBV7-2 gene
      segment, a conserved Arg residue in the complementarity-determining region (CDR)
      3beta loop and prevalent usage of the canonical ASSxRxTDTQY CDR3beta loop among T
      cells with this specificity. In 30 clones that had the canonical TCRbeta chain,
      we found a strict usage of the TRAV26-1 gene segment in the TCRalpha chain. There
      was variable usage of the TRAJ genes and diverse CDR3alpha sequences with no
      apparent conserved motifs. This study extends previous reports on biased TCR
      usage in both HLA-DQ2.5- and DQ8-restricted gluten-specific TCRs and provides
      data for further studies on TRAV and TRBV pairing.

PMID- 24038602
TI  - The AP-1 transcription factor JunD activates the leukocyte immunoglobulin-like
      receptor 1 distal promoter.
AB  - Leukocyte immunoglobulin-like receptor 1 (LILRB1) is an inhibitory receptor that
      binds classical and non-classical MHC-I as well as UL18, a viral MHC-I homolog.
      LILRB1 is encoded within the leukocyte receptor complex and is widely expressed
      on immune cells. Two distinct promoters used differentially by lymphoid and
      myeloid cells were previously identified, but little is known regarding molecular
      regulation of each promoter or cell-type-specific usage. Here, we have
      investigated the transcriptional regulation of human LILRB1 focusing on elements
      that drive expression in NK cells. We found that while both the distal and
      proximal promoter regions are active in reporter plasmids in lymphoid and myeloid
      cells, the proximal promoter is used minimally to transcribe LILRB1 in NK cells
      compared with monocytes. We defined a 120-bp core region of transcriptional
      activity in the distal promoter that can bind several factors in NK cell nuclear
      extracts. Within this region, we investigated overlapping putative AP-1 sites. An
      inhibitor of JNK decreased LILRB1 transcript in a LILRB1+ NK cell line. Upon
      examining binding of specific AP-1 factors, we found JunD associated with the
      LILRB1 distal promoter. Finally, depletion of JunD led to a decrease in distal
      promoter transcript, indicating an activating role for JunD in regulation of
      LILRB1 transcription. This study presents the first description of
      regions/factors required for activity of the LILRB1 distal promoter, the first
      description of a role for JunD in NK cells and suggests a potential mechanism for
      dynamic regulation of LILRB1 by cytokines.

PMID- 24038603
TI  - Activation of pluripotency genes by a nanotube-mediated protein delivery system.
AB  - The overexpression of cell reprogramming factors (Oct4, Sox2, Klf4, Nanog, and c
      Myc) allows differentiated cells to revertto an earlier developmental stage.
      Differentiated cells can also be reprogrammed by directly delivering
      reprogramming proteins tagged with cell-penetrating peptides, which allow the
      proteins to pass through the cell membrane and into the cytoplasm-although this
      method has been an inefficient process. Here, we describe a novel technique for
      delivering reprogramming proteins into cells using titanium oxide (TiO2 )
      nanotubes, which show no cytotoxic effects and do not affect cell proliferation.
      TiO2 nanotubes successfully transferred the above-mentioned reprogramming factors
      into differentiated somatic cells. After 3 weeks of treatment with protein
      conjugated nanotubes, the somatic cells adopted an embryonic stem cell-like
      morphology and expressed activated Oct4-green fluorescent protein, a pluripotency
      biomarker. Our results indicate that TiO2 nanotubes can be used to directly
      deliver reprogramming factors into somatic cells to induce pluripotency.

PMID- 24038605
TI  - Combating multidrug-resistant bacteria: current strategies for the discovery of
      novel antibacterials.
AB  - The introduction of effective antibacterial therapies for infectious diseases in
      the mid-20th century completely revolutionized clinical practices and helped to
      facilitate the development of modern medicine. Many potentially life-threatening
      conditions became easily curable, greatly reducing the incidence of death or
      disability resulting from bacterial infections. This overwhelming historical
      success makes it very difficult to imagine life without effective antibacterials;
      however, the inexorable rise of antibiotic resistance has made this a very real
      and disturbing possibility for some infections. The ruthless selection for
      resistant bacteria, coupled with insufficient investment in antibacterial
      research, has led to a steady decline in the efficacy of existing therapies and a
      paucity of novel structural classes with which to replace them, or complement
      their use. This situation has resulted in a very pressing need for the discovery
      of novel antibiotics and treatment strategies, the development of which is likely
      to be a key challenge to 21st century medicinal chemistry. 

PMID- 24038606
TI  - Multi-step spin crossover accompanied by symmetry breaking in an Fe(III) complex:
      crystallographic evidence and DFT studies.
AB  - Spin doctor: A mononuclear ferric complex [Fe(H-5-Br-thsa)(5-Br-thsa)]?H2O (1)
      (H2-5-Br-thsa = 5-bromo-2-hydroxybenzylidene)hydrazinecarbothioamide) was
      synthesized and its magnetic properties and structure were investigated by DFT
      calculations. This complex shows unprecedented reversible, six/five-step spin
      crossover behavior accompanied by symmetry breaking. More importantly, each step
      in the multi-step transition was successfully characterized by single-crystal X
      ray diffraction.

PMID- 24038604
TI  - To fuse or not to fuse: what is your purpose?
AB  - Since the dawn of time, or at least the dawn of recombinant DNA technology (which
      for many of today's scientists is the same thing), investigators have been
      cloning and expressing heterologous proteins in a variety of different cells for
      a variety of different reasons. These range from cell biological studies looking
      at protein-protein interactions, post-translational modifications, and
      regulation, to laboratory-scale production in support of biochemical,
      biophysical, and structural studies, to large scale production of potential
      biotherapeutics. In parallel, fusion-tag technology has grown-up to facilitate
      microscale purification (pull-downs), protein visualization (epitope tags),
      enhanced expression and solubility (protein partners, e.g., GST, MBP, TRX, and
      SUMO), and generic purification (e.g., His-tags, streptag, and FLAGTM-tag).
      Frequently, these latter two goals are combined in a single fusion partner. In
      this review, we examine the most commonly used fusion methodologies from the
      perspective of the ultimate use of the tagged protein. That is, what are the most
      commonly used fusion partners for pull-downs, for structural studies, for
      production of active proteins, or for large-scale purification? What are the
      advantages and limitations of each? This review is not meant to be exhaustive and
      the approach undoubtedly reflects the experiences and interests of the authors.
      For the sake of brevity, we have largely ignored epitope tags although they
      receive wide use in cell biology for immunopreciptation. 

PMID- 24038608
TI  - Point-of-care testing: where is the evidence? A systematic survey.
AB  - Point-of-care testing (POCT) has had rapid technological development and their
      use is widespread in clinical laboratories to assure reduction of turn-around
      time and rapid patient management in some clinical settings where it is important
      to make quick decisions. Until now the papers published about the POCT have
      focused on the reliability of the technology used and their analytical accuracy.
      We aim to perform a systematic survey of the evidence of POCT efficacy focused on
      clinical outcomes, selecting POCT denoted special analytes characterized by
      possible high clinical impact. We searched in Medline and Embase. Two independent
      reviewers assessed the eligibility, extracted study details and assessed the
      methodological quality of studies. We analyzed 84 studies for five POCT
      instruments: neonatal bilirubin, procalcitonin, intra-operative parathyroid
      hormone, troponin and blood gas analysis. Studies were at high risk of bias. Most
      of the papers (50%) were studies of correlation between the results obtained by
      using POCT instruments and those obtained by using laboratory instruments. These
      data showed a satisfactory correlation between methods when similar analytical
      reactions were used. Only 13% of the studies evaluated the impact of POCT on
      clinical practice. POCT decreases the time elapsed for making decisions on
      patient management but the clinical outcomes have never been adequately
      evaluated. Our work shows that, although POCT has the potential to provide
      beneficial patient outcome, further studies may be required, especially for
      defining its real utility on clinical decision making.

PMID- 24038609
TI  - Free flap failure in head and neck reconstruction.
AB  - BACKGROUND: The purpose of this study was to determine the causes of head and
      neck free flap loss and to evaluate outcomes after subsequent microvascular and
      non-microvascular reconstruction. METHODS: Patients who experienced free flap
      loss between 2000 and 2012 were reviewed. RESULTS: There were 40 flap losses out
      of 3090 free flaps (1.3%). Twenty-eight patients underwent subsequent free flap
      reconstruction of which 27 free flaps were successful (96.4%), which was not
      significantly different from our initial flap success rate (p = .81). Of patients
      who underwent subsequent free flap reconstruction for oral/pharyngeal defects,
      100% had >80% speech intelligibility and 87.5% were tube feed independent. By
      comparison, 42.9% of patients who underwent subsequent pectoralis major flap
      reconstruction had intelligible speech (p = .01) and 25.0% were independent of
      tube feeds (p = 0.02). CONCLUSION: Subsequent free flaps after initial free flap
      losses can be successful in selected patients. Functional outcomes after
      subsequent free flap reconstruction are favorable compared to pedicled flap
      reconstruction.

PMID- 24038607
TI  - SAS1B protein [ovastacin] shows temporal and spatial restriction to oocytes in
      several eutherian orders and initiates translation at the primary to secondary
      follicle transition.
AB  - BACKGROUND: Sperm Acrosomal SLLP1 Binding (SAS1B) protein (ovastacin) is an
      oolemmal binding partner for the intra-acrosomal sperm protein SLLP1. RESULTS:
      Immunohistochemical localization revealed that SAS1B translation is restricted
      among adult tissues to the ovary and oocytes, SAS1B appearing first in follicles
      at the primary-secondary transition. Quiescent oocytes within primordial
      follicles and primary follicles did not stain for SAS1B. Examination of neonatal
      rat ovaries revealed SAS1B expression first as faint signals in postnatal day 3
      oocytes, with SAS1B protein staining intensifying with oocyte growth.
      Irrespective of animal age or estrus stage, SAS1B was seen only in oocytes of
      follicles that initiated a second granulosa cell layer. The precise temporal and
      spatial onset of SAS1B expression was conserved in adult ovaries in seven
      eutherian species, including nonhuman primates. Immunoelectron micrographs
      localized SAS1B within cortical granules in MII oocytes. A population of SAS1B
      localized on the oolemma predominantly in the microvillar region anti-podal to
      the nucleus in ovulated MII rat oocytes and on the oolemma in macaque GV oocytes.
      CONCLUSIONS: The restricted expression of SAS1B protein in growing oocytes,
      absence in the ovarian reserve, and localization on the oolemma suggest this zinc
      metalloprotease deserves consideration as a candidate target for reversible
      female contraceptive strategies.

PMID- 24038610
TI  - The effects of hypothyroidism on the proximal femoral physis in miniature swine.
AB  - As a potential means of comparing hypothyroidism in humans, this work intended to
      establish a defined hypothyroid state in immature miniature swine and evaluate
      specific molecular, cellular, and extracellular responses of their growth plates.
      Two male, 11-week-old Sinclair miniature swine were given 6-propyl-2-thiouracil
      (PTU) in their water and two other like animals (controls) were provided water
      without PTU. Blood levels of thyroid stimulating hormone (TSH), triiodothyronine
      (T3), and thyroxin (T4) were monitored weekly. At 25 weeks of age, the hind limb
      proximal femoral physes were harvested and divided into portions for histology
      and reverse transcription-quantitative polymerase chain reaction (RT-qPCR)
      analysis. Compared to controls, swine administered PTU exhibited increased TSH
      and decreased T3 and T4 serum levels during the study period, features consistent
      with a hypothyroid state. Compared to controls, hypothyroid swine exhibited
      structurally altered physes and demonstrated significantly decreased gene
      expression of aggrecan (p < 0.05) and type X collagen (p <= 0.1). This is the
      first hypothyroid model established in miniature swine and represents a
      potentially important advance for understanding the condition in humans, in
      which, like this swine model, there are changes critical to growth plate
      molecular biology, biochemistry and structure.

PMID- 24038611
TI  - Recovery based on plot experiments is a poor predictor of landscape-level
      population impacts of agricultural pesticides.
AB  - Current European Union regulatory risk assessment allows application of
      pesticides provided that recovery of nontarget arthropods in-crop occurs within a
      year. Despite the long-established theory of source-sink dynamics, risk
      assessment ignores depletion of surrounding populations and typical field trials
      are restricted to plot-scale experiments. In the present study, the authors used
      agent-based modeling of 2 contrasting invertebrates, a spider and a beetle, to
      assess how the area of pesticide application and environmental half-life affect
      the assessment of recovery at the plot scale and impact the population at the
      landscape scale. Small-scale plot experiments were simulated for pesticides with
      different application rates and environmental half-lives. The same pesticides
      were then evaluated at the landscape scale (10 km * 10 km) assuming continuous
      year-on-year usage. The authors' results show that recovery time estimated from
      plot experiments is a poor indicator of long-term population impact at the
      landscape level and that the spatial scale of pesticide application strongly
      determines population-level impact. This raises serious doubts as to the utility
      of plot-recovery experiments in pesticide regulatory risk assessment for
      population-level protection. Predictions from the model are supported by
      empirical evidence from a series of studies carried out in the decade starting in
      1988. The issues raised then can now be addressed using simulation. Prediction of
      impacts at landscape scales should be more widely used in assessing the risks
      posed by environmental stressors.

PMID- 24038612
TI  - Ligand- and stage-dependent divergent functions of BMP signaling in the
      differentiation of embryonic skeletogenic progenitors in vitro.
AB  - Bone morphogenetic proteins (BMPs) are key molecules in the differentiation of
      skeletal tissues. We have investigated whether differentiation of limb embryonic
      mesodermal progenitors into different connective tissue lineages depends on
      specific stimulation of distinct BMP ligands or on the differential response of
      target cells to a common BMP stimulus. We show that Bmp2,4,5,7 and Gdf5 exhibit
      differential expression domains during the formation of tendons, cartilages, and
      joint tissues in digit development, but their respective effects on digit
      progenitors cell cultures cannot sustain the divergent differentiation of these
      cells into tendons, joints, and cartilage. However, the influence of BMPs differs
      based on the culture length. Early cultures respond to any of the BMPs by
      inducing chondrogenic factors and inhibiting fibrogenic and osteogenic markers.
      Later, a second phase of the culture occurs when BMPs attenuate their
      prochondrogenic influence and promote the fibrogenic marker Scleraxis. At
      advanced culture stages, BMPs inhibit prochondrogenic and profibrogenic markers
      and promote osteogenic markers. The switch from the prochondrogenic to the
      profibrogenic response appears critically dependent on the basal expression of
      Noggin. Thus, the differential regulation of Scleraxis at these stages was
      abrogated by treatments with a BMP-analogous compound (AB204) that escapes NOGGIN
      antagonism. Gene regulation experiments in absence of protein synthesis during
      the first period of culture indicate that BMPs activate at the same time master
      chondrogenic and fibrogenic genes together with cofactors responsible for driving
      the signaling cascade toward chondrogenesis or fibrogenesis. Gene-silencing
      experiments indicate that Id2 is one of the factors limiting the profibrogenic
      influence of BMPs. We propose that connective tissues are dynamic structures
      composed of cartilage, fibrous tissue, and bone that form in successive steps
      from the differentiation of common progenitors. This sequential differentiation
      is regulated by BMPs through a process that is dependent on the basal expression
      of BMP cofactors or signaling modulators.

PMID- 24038613
TI  - The role of parenting stress in young children's mental health functioning after
      exposure to family violence.
AB  - This study evaluates the associations of young children's exposure to family
      violence events, parenting stress, and children's mental health functioning.
      Caregivers provided data for 188 children ages 3 to 5 years attending Head Start
      programming. Caregivers reported 75% of children had experienced at least 1 type
      of trauma event, and 27% of children had experienced a family violence event.
      Child mental health functioning was significantly associated with family violence
      exposure after controlling for children's age, gender, household income, and
      other trauma exposure (beta = .14, p = .033). Stress in the parenting role
      partially mediated the relationship between family violence exposure and young
      children's mental health functioning (beta = .12, p = .015, 95% confidence
      interval [0.02, 0.21]). Interventions for young children exposed to family
      violence should address the needs of the child, as well as the caregiver while
      also building healthy parent-child relationships to facilitate positive outcomes
      in children faced with trauma. 

PMID- 24038614
TI  - The representation of oral fat texture in the human somatosensory cortex.
AB  - How fat is sensed in the mouth and represented in the brain is important in
      relation to the pleasantness of food, appetite control, and the design of foods
      that reproduce the mouthfeel of fat yet have low energy content. We show that the
      human somatosensory cortex (SSC) is involved in oral fat processing via
      functional coupling to the orbitofrontal cortex (OFC), where the pleasantness of
      fat texture is represented. Using functional MRI, we found that activity in SSC
      was more strongly correlated with the OFC during the consumption of a high fat
      food with a pleasant (vanilla) flavor compared to a low fat food with the same
      flavor. This effect was not found in control analyses using high fat foods with a
      less pleasant flavor or pleasant-flavored low fat foods. SSC activity correlated
      with subjective ratings of fattiness, but not of texture pleasantness or flavor
      pleasantness, indicating a representation that is not involved in hedonic
      processing per se. Across subjects, the magnitude of OFC-SSC coupling explained
      inter-individual variation in texture pleasantness evaluations. These findings
      extend known SSC functions to a specific role in the processing of pleasant
      flavored oral fat, and identify a neural mechanism potentially important in
      appetite, overeating, and obesity.

PMID- 24038615
TI  - Chemical diversification of sialic acid glycosides by stereospecific,
      chemoselective deamination.
AB  - Late bloomer: Nitrosation of peracetylated sialic acid glycosides followed by
      treatment with sodium trifluoroethoxide and then a suitable nucleophile enables
      the late-stage modification of these glycosides with stereospecific replacement
      of the acetamido group. This method should enable access to many glycoside
      derivatives with a minimum of synthetic effort. 

PMID- 24038616
TI  - Wild type and mutants of the HET-s(218-289) prion show different flexibility at
      fibrillar ends: a simulation study.
AB  - The C-terminal segment (residues 218-289) of the HET-s protein of the filamentous
      fungus Podosporina anserina is a prion-forming domain. The structural model of
      the HET-s(218-289) amyloid fibril based on solid-state nuclear magnetic resonance
      (NMR) restraints shows a beta solenoid topology which is comprised of a beta
      sheet core and interconnecting loops. For the single-point mutants Phe286Ala and
      Trp287Ala, slower aggregation rates in vitro and loss of prionic infectivity have
      been reported recently. Here we have used molecular dynamics to compare the
      flexibility of the mutants and wild type. The simulations, initiated from a
      trimeric aggregate extracted from the NMR structural model, show structural
      stability on a 100-ns time scale for wild type and mutants. Analysis of the
      fluctuations along the simulations reveals that the mutants are less flexible
      than the wild type in the C-terminal segment at only one of the two external
      monomers. Analysis of interaction energy and buried accessible surface indicates
      that residue Phe286 in particular is stabilized in the Trp287Ala mutant. The
      simulation results provide an atomistic explanation of the suggestion (based on
      indirect experimental evidence) that flexibility at the protofibril end(s) is
      required for fibril elongation. Moreover, they provide further evidence that the
      growth of the HET-s amyloid fibril is directional.

PMID- 24038617
TI  - Inhibition of hydroxycinnamic acid sulfation by flavonoids and their conjugated
      metabolites.
AB  - Hydroxycinnamic acids and flavonoids are dietary phenolic antioxidants that are
      abundant in our diet. Hydroxycinnamic acids are highly sulfated in vivo, and
      sulfotransferases (SULTs), in particular SULT1A1, play a major role in their
      metabolism. Flavonoids are potent inhibitors of human SULTs. In this study, the
      potential metabolic interaction between dietary hydroxycinnamic acids and
      flavonoids was investigated. Flavonoids, such as luteolin, quercetin, daidzein,
      and genistein, are identified as potent inhibitors of hydroxycinnamic acid
      sulfation in human liver S9 homogenate with IC50 values <1 uM. The inhibitory
      activity was less potent in the human intestinal S9 homogenate. We also
      demonstrate that quercetin conjugates found in vivo (quercetin-3-O-glucuronide,
      quercetin-7-O-glucuronide, and quercetin-3'-O-sulfate) moderately inhibited the
      sulfation of hydroxycinnamic acids in human liver S9. In an intact cellular
      system, human HepG2 cells, caffeic acid and ferulic acid sulfation was inhibited
      by luteolin and quercetin (IC50 : 1.6-3.9 uM). Quercetin-3'-O-sulfate weakly
      inhibited sulfation. Quercetin glucuronides, limited by their low cellular
      uptake, were ineffective. These data suggest that the inhibition of SULTs by
      flavonoids and in vivo flavonoid conjugates may modify the bioavailability of
      dietary hydroxycinnamic acids by suppressing their conversion to sulfated
      metabolites.

PMID- 24038618
TI  - Inflammatory responses and morphological changes of radiofrequency-induced rat
      sciatic nerve fibres.
AB  - BACKGROUND: Recently, the pulsed radiofrequency (PRF, pulsed fashion) procedure
      was introduced for neuropathic pain management. Since PRF-induced lesions do not
      need high temperature compared with conventional continuous RF (CRF)-induced
      lesions, there is no significant loss of sensory fibres after application.
      METHODS: The progressive changes in the expression of eight representative
      inflammatory cytokines - glial fibrillary acidic protein, tumour necrosis factor
      alpha, interleukin-6, cyclooxygenase-II, inducible nitric oxide synthase, nuclear
      factor-kappaB, monocyte chemoattractant protein-1 and macrophage inflammatory
      protein-1alpha - as well as the morphological changes in extracellular matrices
      by Masson's trichrome and Verhoeff-van Gieson staining and atomic force
      microscopy were assessed for normal (control), sham (no RF current), PRF and CRF
      (positive control) rats. The RF procedure used in this study was similar to the
      methods used in human clinical trials. RESULTS: All proposed inflammatory
      proteins showed up-regulation after RF thermal treatments. Specifically, PRF
      treated rats showed recovery of up-regulated inflammatory cytokines on day 30
      after application, while CRF rats showed significant up-regulation that persisted
      until day 30. The control and sham groups showed normal unmyelinated axon and
      collagen structures. PRF-induced lesions showed less fibre destruction than CRF
      induced lesions. PRF-induced lesions also showed mild axonal damage and little
      swelling of the mitochondria. CRF-induced lesions showed ultrastructural changes
      of sciatic nerve fibres that were irreversible. CONCLUSIONS: PRF-induced pain
      relief may be due to temporary blockage of nerve signals through the nerve
      pathway responsible for reversible neuronal depression. However, CRF-induced pain
      relief may be due to permanent blockage of nerve signals through other nerve
      pathways. Therefore, CRF could be applied to chronic inflammatory models used to
      study the mechanism of neuropathic pain.

PMID- 24038619
TI  - Precise patterning of silk microstructures using photolithography.
AB  - Photolithography is used in conjunction with a "silk fibroin photoresist" to form
      precise protein microstructures directly and rapidly on a variety of substrates.
      High-resolution features in two and three dimensions with line widths down to one
      micrometer are formed. Photo-crosslinked protein structures guide cell adhesion,
      providing precise spatial control of cells without requiring adhesive ligands. 

PMID- 24038620
TI  - The epidemiology of psychiatric disorders among women with breast cancer in South
      Korea: analysis of national registry data.
AB  - OBJECTIVE: Population-based data on the epidemiology of psychiatric disorders in
      patients with breast cancer are lacking. Because the National Health Insurance
      (NHI) Program in South Korea is a compulsory social insurance system covering the
      entire Korean population, the NHI is a good source of information for
      epidemiological studies. In the present study, we examined the incidence of
      psychiatric disorders among Korean women newly diagnosed with breast cancer using
      the NHI Corporation (NHIC) database. METHODS: Data were collected for adult women
      newly diagnosed with breast cancer using the claim database and cancer
      registration files of the NHIC from 2005 to 2008. We analysed data for women
      diagnosed with psychiatric disorders over a 5-year period, from 2004 (at least 1
      year before the cancer registration date) to 2009 (at least 1 year after the
      cancer registration date). RESULTS: We identified 6536 patients with psychiatric
      disorders among 42 190 women with breast cancer. The most prevalent psychiatric
      disorder was anxiety disorder (N = 2518). The incidence rates of anxiety
      disorders, depressive disorders, sleep disorders and adjustment disorders were
      27.08, 22.41, 10.57 and 4.35 cases per 1000 person-year, respectively.
      CONCLUSION: The incidence rates of psychiatric disorders in Korean women with
      breast cancer from the nationwide database were much lower than found by previous
      reports using screening tools. The finding implicates that psychiatric disorders
      among breast cancer patients tend to be underdiagnosed and undertreated in actual
      clinical practice. Our epidemiological findings provide important information for
      establishing a national strategy of cancer care to detect and manage psychiatric
      problems.

PMID- 24038621
TI  - A short total synthesis of the marine sponge pyrrole-2-aminoimidazole alkaloid
      (+/-)-agelastatin A.

PMID- 24038622
TI  - Mechanistic investigation of domain specific unfolding of human serum albumin and
      the effect of sucrose.
AB  - This study is devoted to understand the unfolding mechanism of a multidomain
      protein, human serum albumin (HSA), in absence and presence of the sucrose by
      steady-state and time-resolved fluorescence spectroscopy with domain specific
      marker molecules and is further being substantiated by molecular dynamics (MD)
      simulation. In water, the domain III of HSA found to unfold first followed by
      domains I and II as the concentration of GnHCl is increased in the medium. The
      sequential unfolding behavior of different domains of HSA remains same in
      presence of sucrose; however, a higher GnHCl concentration is required for
      unfolding, suggesting stabilizing effect of sucrose on HSA. Domain I is found to
      be most stabilized by sucrose. The stabilization of domain II is somewhat similar
      to domain I, but the effect of sucrose on domain III is found to be very small.
      MD simulation also predicted a similar behavior of sucrose on HSA. The
      stabilizing effect of sucrose is explained in terms of the entrapment of water
      molecules in between HSA surface and sucrose layer as well as direct interaction
      between HSA and sucrose. 

PMID- 24038624
TI  - Insertion of CS(2) into iridium-fluorine bonds.
AB  - CS2 jumps in: C?F bond formation occurs by reactions of the fluorido complexes
      trans-[Ir(Ar(F) )(F)(H)(PiPr3 )2 ] (Ar(F) =4-C5 NF4 ; see scheme) with CS2 to
      form the fluorodithiocarbonato species trans-[Ir(Ar(F) )(H)(kappa(2) -(S,S)-S2
      CF)(PiPr3 )2 ]. DFT studies suggest an unprecedented concerted metathesis-like
      mechanism for the C?F bond-formation step in which CS2 inserts into the Ir?F
      bond. 

PMID- 24038623
TI  - The subventricular zone is able to respond to a demyelinating lesion after
      localized radiation.
AB  - Radiation is a common tool in the treatment of brain tumors that induces
      neurological deficits as a side effect. Some of these deficits appear to be
      related to the impact of radiation on the neurogenic niches, producing a drastic
      decrease in the proliferative capacity of these regions. In the adult mammalian
      brain, the subventricular zone (SVZ) of the lateral ventricles is the main
      neurogenic niche. Neural stem/precursor cells (NSCs) within the SVZ play an
      important role in brain repair following injuries. However, the irradiated NSCs'
      ability to respond to damage has not been previously elucidated. In this study,
      we evaluated the effects of localized radiation on the SVZ ability to respond to
      a lysolecithin-induced demyelination of the striatum. We demonstrated that the
      proliferation rate of the irradiated SVZ was increased after brain damage and
      that residual NSCs were reactivated. The irradiated SVZ had an expansion of
      doublecortin positive cells that appeared to migrate from the lateral ventricles
      toward the demyelinated striatum, where newly generated oligodendrocytes were
      found. In addition, in the absence of demyelinating damage, remaining cells in
      the irradiated SVZ appeared to repopulate the neurogenic niche a year post
      radiation. These findings support the hypothesis that NSCs are radioresistant and
      can respond to a brain injury, recovering the neurogenic niche. A more complete
      understanding of the effects that localized radiation has on the SVZ may lead to
      improvement of the current protocols used in the radiotherapy of cancer.

PMID- 24038625
TI  - Rh(III) -catalyzed C-H activation: a versatile route towards various polycyclic
      pyridinium salts.
AB  - An efficient and convenient method for the synthesis of highly substituted
      polycyclic pyridinium salts from the reaction of various 2-aryl-pyridines and 2
      aryl-sp(2) -nitrogen-atom-containing heterocycles with alkynes through
      rhodium(III)-catalyzed C?H activation and annulation under an O2 atmosphere is
      described. A possible mechanism that involves the chelation-assisted C?H
      activation of the 2-aryl-pyridine substrate, insertion of the alkyne, and
      reductive elimination is proposed. This mechanism was supported by the isolation
      of a five-membered rhodacycle (I'). In addition, kinetic isotope studies were
      performed to understand the intimate reaction mechanism. 

PMID- 24038626
TI  - Surgical outcomes of robotic thyroid surgery using a double incision gasless
      transaxillary approach: analysis of 400 cases treated by the same surgeon.
AB  - BACKGROUND: The purpose of this study was to evaluate the surgical outcomes of
      400 cases of robotic thyroid surgery using a double incision gasless
      transaxillary approach. METHODS: We analyzed 400 patients who underwent a robot
      assisted thyroidectomy performed by a single surgeon. RESULTS: All patients
      underwent successful operations without conversion to open surgery. Transient
      hypoparathyroidism was the most common complication (51.7%) and permanent
      hypoparathyroidism occurred in only 2 patients (1.4%). The mean number of
      retrieved central lymph nodes was 6.5 +/- 4.4 for ipsilateral central compartment
      node dissection and 8.4 +/- 5.1 for bilateral central compartment node
      dissection. The proportion of patients with stimulated thyroglobulin (sTg) levels
      at the time of remnant ablation <10 ng/mL and sTg levels 6 to 12 months after the
      first ablation <1 ng/mL was 84.9% and 88.3%, respectively. CONCLUSION: Robotic
      thyroid surgery is technically safe and may be a surgical option for patients
      with well-differentiated thyroid cancer.

PMID- 24038627
TI  - Phylogeny and expression of canonical transient receptor potential (TRPC) genes
      in developing zebrafish.
AB  - BACKGROUND: Canonical transient receptor potential (TRPC) channels are
      nonselective, calcium-permeable cation channels that are expressed in a great
      variety of organisms, tissues, and cell types. TRPC channels are known to be
      involved in the transduction of polymodal sensory input. Additionally, they are
      implicated in a variety of developmental processes. Distinct gating mechanisms
      have been elucidated so far, but their exact functional role in vertebrate
      organisms still needs to be resolved. RESULTS: We now used the teleost Danio
      rerio to perform a comprehensive expression analysis of the trpc gene subfamily.
      Based on the sequence homology to the seven described mammalian TRPC channels, we
      identified 12 trpc genes in the zebrafish genome. All but trpc1 and trpc3 are
      represented by two paralogs. We further describe the specific expression patterns
      of trpc transcripts in whole-mounts during the first 5 days of development.
      CONCLUSIONS: Consistent with their proposed role in sensory transduction
      zebrafish trpcs are predominantly expressed in neural structures such as the
      olfactory, visual, mechanosensitive, and motor systems. Intriguingly, zebrafish
      paralogs show mainly nonoverlapping expression patterns, suggesting that
      duplicated genes have either split their functions or have adapted new ones.

PMID- 24038628
TI  - Biolinguistics: forays into human cognitive biology.
AB  - The present article surveys the field of biolinguistics. It revisits the roots of
      the field's core research agenda, then turns to the various factors that led to
      its recent re-emergence, and finally offers suggestions for future inquiry. The
      essay also serves to highlight certain conceptual issues that should be addressed
      if the field is to bear its interdisciplinary fruits. 

PMID- 24038629
TI  - Evolutionary insights into global patterns of human cranial diversity: population
      history, climatic and dietary effects.
AB  - The study of cranial variation has a long, and somewhat difficult, history within
      anthropology. Much of this difficulty is rooted in the historical use of
      craniometric data to justify essentialist typological racial classification
      schemes. In the post-war era of the "New Physical Anthropology" (sensu Washburn,
      1951), anthropologists began to analyse human variation in an explicitly
      populationist and evolutionary philosophical and analytical framework. However,
      even within recent decades, substantially different approaches have been
      employed; some advocate a focus on the analysis of individual traits or clines,
      while others are explicitly adaptationist, with a focus on natural selection as
      the preeminent force of phenotypic diversification. In recent years, a series of
      studies have analysed craniometric data in an explicitly quantitative genetic
      framework, which emphasises the importance of neutral forces such as migration,
      gene flow and genetic drift in creating global patterns of phenotypic diversity.
      This approach has revealed that global patterns of cranial variation can largely
      be explained on the basis of neutral theory. Therefore, human cranial data can be
      productively employed as a proxy for neutral genetic data in archaeological
      contexts. Moreover, there is a growing recognition that regions of the cranium
      differ in the extent to which they fit a neutral model of microevolutionary
      expectation, allowing for a more detailed assessment of patterns of adaptation
      and phenotypic plasticity within the human skull. Taking an historical
      perspective, the current state of knowledge regarding patterns of cranial
      adaptation in response to climatic and dietary effects is reviewed. Further
      insights will be gained by better incorporating the study of cranial and
      postcranial variation, as well as understanding the impact of neutral versus non
      neutral evolution in creating among-species diversity patterns in primates more
      generally. However, this will most effectively be achieved when comparative
      anatomy studies are situated within an explicitly quantitative genetic
      evolutionary framework. 

PMID- 24038630
TI  - Novel pharmacological agents targeting memory and cognition in the treatment of
      anxiety disorders.
AB  - OBJECTIVE: The aim of this study is to review data for several promising novel
      pharmacological drugs for anxiety disorders and describe how they exert their
      effects. METHOD: We presented a review of the published literature. Online search
      plus reference list checking was also used. RESULTS: The neurobiology of anxiety
      is overviewed. N-methyl-D-aspartate and beta adrenaline are involved in memory
      consolidation. We describe studies using memantine, D-cycloserine, propranolol,
      and riluzole that modulate these pathways. CONCLUSION: There are a number of
      promising new therapies, but these require further studies before they can enter
      routine clinical practice.

PMID- 24038631
TI  - Towards the development of flexible non-volatile memories.
AB  - Flexible non-volatile memories have attracted tremendous attentions for data
      storage for future electronics application. From device perspective, the
      advantages of flexible memory devices include thin, lightweight, printable,
      foldable and stretchable. The flash memories, resistive random access memories
      (RRAM) and ferroelectric random access memory/ferroelectric field-effect
      transistor memories (FeRAM/FeFET) are considered as promising candidates for next
      generation non-volatile memory device. Here, we review the general background
      knowledge on device structure, working principle, materials, challenges and
      recent progress with the emphasis on the flexibility of above three categories of
      non-volatile memories. 

PMID- 24038632
TI  - Spiro[4,4]-1,6-nonadiene-based diphosphine oxides in lewis base catalyzed
      asymmetric double-aldol reactions.
AB  - Symmetry swap: A C2 -chiral spiro diphosphine oxide (SpinPO) has been found to be
      highly efficient and enantioselective in the catalysis of double-aldol reactions
      of ketones and aldehydes to give the corresponding optically active double-aldol
      products, which can be readily transformed into optically active C3 - and pseudo
      C3 -symmetric molecules. 

PMID- 24038633
TI  - Assembling DNA through affinity binding to achieve ultrasensitive protein
      detection.
AB  - Recent advances in DNA assembly and affinity binding have enabled exciting
      developments of nanosensors and ultrasensitive assays for specific proteins.
      These sensors and assays share three main attractive features: 1) the detection
      of proteins can be accomplished by the detection of amplifiable DNA, thereby
      dramatically enhancing the sensitivity; 2) assembly of DNA is triggered by
      affinity binding of two or more probes to a single target molecule, thereby
      resulting in increased specificity; and 3) the assay is conducted in solution
      with no need for separation, thus making the assay attractive for potential point
      of-care applications. We illustrate here the principle of assembling DNA through
      affinity binding, and we highlight novel applications to the detection of
      proteins.

PMID- 24038634
TI  - Selection bias in pharmacy-based patient surveys.
AB  - PURPOSE: To evaluate if there is a selection bias in drug utilization surveys on
      prescription drugs regularly conducted in Swedish pharmacies, to describe the
      direction of this potential bias and discuss the implications for the results.
      METHODS: Age and gender distributions within patient survey samples from drug
      utilization surveys conducted during 2006-2010 are compared to the age and gender
      distribution of all Swedish patients, receiving the same drug or drugs, as given
      by the Swedish Prescribed Drug Register. The differences between the proportions
      of patients within the age and gender segments of each pair of survey/register
      data were calculated. RESULTS: In 25 (81%) out of 31 included surveys, patients
      aged 75 years or older are significantly underrepresented, as they are less
      likely to visit the pharmacy to collect their prescription drugs themselves and
      thus disqualify for the interviews. Data on women show similar results as overall
      survey data, whereas the underrepresentation of the oldest age group among men
      appears in a lower proportion of the surveys, 67%. The general consequence is a
      selection towards a healthier survey sample, but the consequences in the
      individual surveys vary, depending on what drug is being studied. CONCLUSION:
      Pharmacy-based patient surveys provide a convenient data collection method for
      patient self-reported data, but patients aged 75 years or older are consistently
      underrepresented. In surveys where this may influence the main research question,
      data should also be collected with other methods reaching the oldest patients.

PMID- 24038635
TI  - Skin cancer as a marker of sun exposure associates with myocardial infarction,
      hip fracture and death from any cause.
AB  - BACKGROUND: Sun exposure is the single most important risk factor for skin
      cancer, but sun exposure may also have beneficial effects on health. We tested
      the hypothesis that individuals with skin cancer (non-melanoma skin cancer and
      cutaneous malignant melanoma) have less myocardial infarction, hip fracture and
      death from any cause, compared with general population controls. METHODS: We
      examined the entire Danish population above age 40 years from 1980 through 2006,
      comprising 4.4 million individuals. Diagnoses of non-melanoma skin cancer
      (n=129,206), cutaneous malignant melanoma (n=22,107), myocardial infarction
      (n=327,856), hip fracture (n=129,419), and deaths from any cause (n=1,629,519)
      were drawn from national registries. RESULTS: In individuals with vs without non
      melanoma skin cancer, multifactorially adjusted odds ratios were 0.96 (95%
      confidence interval: 0.94-0.98) for myocardial infarction and 1.15 (1.12-1.18)
      for hip fracture, and the multifactorially adjusted hazard ratio was 0.52 (0.52
      0.53) for death from any cause. Risk of hip fracture was reduced (odds ratios
      were below 1.0) in individuals below age 90 years. In individuals with vs without
      cutaneous malignant melanoma, corresponding odds ratios were 0.79 (0.74-0.84) for
      myocardial infarction and 0.84 (0.76-0.93) for hip fracture, and the
      corresponding hazard ratio for death from any cause was 0.89 (0.87-0.91);
      however, cutaneous malignant melanoma was associated positively with death from
      any cause in some individuals. CONCLUSIONS: In this nationwide study, having a
      diagnosis of skin cancer was associated with less myocardial infarction, less hip
      fracture in those below age 90 years and less death from any cause. Causal
      conclusions cannot be made from our data. A beneficial effect of sun exposure per
      se needs to be examined in other studies.

PMID- 24038636
TI  - Modeling activation and effective connectivity of VWFA in same script bilinguals.
AB  - Previous neuroimaging research revealed a small area in the inferior occipito
      temporal cortex (VWFA), which seems to be involved in recognition of written
      words. The specialized response of the VWFA to words could result from repeated
      exposure to print in the course of functional fine-tuning of the brain. Research
      with bilingual speakers holds promise in helping to reveal response properties of
      the VWFA by assessing its sensitivity to language proficiency, word-form
      similarity, and meaning overlap across two languages. Using fMRI, we compared
      VWFA activity for cognate and homograph prime-target pairs in a group of fluent
      Spanish-English speakers. Cognates share form and meaning in two languages, while
      homographs only share form. Relative to baseline, the VWFA showed repetition
      suppression to pairs of homographs, but not to pairs of cognates, suggesting that
      this area is sensitive to word meaning. The different response to cognates and
      homographs was only observed when English was the prime language and Spanish was
      the target language. To help explain this result we compared patterns of
      effective connectivity between the VWFA and other parts of the reading network
      implicated in semantic and phonological processing. Our neural models showed that
      English targets engaged a direct ventral route from the VWFA to the frontal lobe
      and Spanish targets engaged an indirect dorsal route. Considering that frontal
      cortex has been implicated in semantic processing, a direct connection to this
      area could signal a fast and automatic access to meaning and would facilitate
      early semantic influences in visual word recognition.

PMID- 24038637
TI  - Suicide ideation and victimization among refugee women along the Thai-Burma
      border.
AB  - Refugee women may experience multiple forms of victimization. The hypotheses
      underlying the present analyses were that experiences of victimization during
      conflict and intimate partner violence (IPV) would be associated with heightened
      odds of suicide ideation among refugee women living in 3 camps along the Thai
      Burma border. Descriptive statistics were generated to describe the prevalence of
      conflict victimization, past-year IPV victimization, past-month suicide ideation,
      and covariates among partnered women with complete data (N = 848) from a cross
      sectional survey conducted in early 2008. Logistic generalized estimating
      equations were used to assess the crude and adjusted relationships between
      variables. The mean age of women was 32.12 years, 91.0% were married, and 78.8%
      were of Karen ethnicity. Overall, 7.4% of women reported past-month suicide
      ideation. Of those women who did not experience any victimization or conflict
      victimization only, 5.1% and 5.2% reported suicide ideation, respectively. By
      contrast 26.7% of women who experienced only IPV victimization reported suicide
      ideation, and 50.0% of women who experienced both forms of victimization reported
      suicide ideation. Understanding each form of violence victimization and their
      relationships to suicide ideation may be important for targeting psychosocial
      services and violence prevention programs within protracted refugee settings. 

PMID- 24038638
TI  - Dynamic kinetic resolution of homoallylic alcohols: application to the synthesis
      of enantiomerically pure 5,6-dihydropyran-2-ones and delta-lactones.
AB  - Dynamic kinetic resolution of various homoallylic alcohols with the use of
      Candida antarctica lipase B and ruthenium catalyst 2 afforded homoallylic
      acetates in high yields and with high enantioselectivity. These enantiopure
      acetates were further transformed into homoallylic acrylates after hydrolysis of
      the ester function and subsequent DMAP-catalyzed esterification with acryloyl
      chloride. After ring-closing metathesis 5,6-dihydropyran-2-ones were obtained in
      good yields. Selective hydrogenation of the carbon?carbon double bond afforded
      the corresponding delta-lactones without loss of chiral information. 

PMID- 24038639
TI  - Solar hydrogen generation by silicon nanowires modified with platinum
      nanoparticle catalysts by atomic layer deposition.
AB  - Covered with Pt: A uniform catalyst profile that ensures effective radial charge
      collection from high-aspect-ratio Si nanowires was achieved by atomic layer
      deposition of Pt nanoparticles. The resulting photoelectrode permits the
      measurement of high photovoltages and low overpotentials, and leads to very good
      stability against photooxidation of Si nanowires in solar water-reduction
      reactions. 

PMID- 24038640
TI  - Data-driven models for protein interaction and design.
AB  - We describe methods and results for four new types of challenge in the Critical
      Assessment of PRedicted Interactions (CAPRI). Two new challenges asked predictors
      to create models related to protein interface design. The first of these was to
      distinguish binding interfaces from designed nonbinding interfaces. The second
      was to predict the effects of all single-point mutations on hemagglutinin binding
      to two small designed proteins. Two additional challenges asked predictors to
      submit high-resolution structures for interface-bound crystallographic waters and
      for binding heparin to a putative glycosylase.

PMID- 24038642
TI  - Disentanglement of donation and back-donation effects on experimental
      observables: a case study of gold-ethyne complexes.
AB  - A charge-displacement analysis of gold-ethyne complexes shows the existence of a
      quantitative relationship between measurable properties and the chemical bond
      constituents in the Dewar-Chatt-Duncanson model. Through suitable experiments,
      these constituents may be disentangled and crucial insight into the nature of
      coordination bonds may thus be gained. 

PMID- 24038641
TI  - Orientationally invariant metrics of apparent compartment eccentricity from
      double pulsed field gradient diffusion experiments.
AB  - Pulsed field gradient diffusion sequences (PFG) with multiple diffusion encoding
      blocks have been indicated to offer new microstructural tissue information, such
      as the ability to detect nonspherical compartment shapes in macroscopically
      isotropic samples, i.e. samples with negligible directional signal dependence on
      diffusion gradients in standard diffusion experiments. However, current
      acquisition schemes are not rotationally invariant in the sense that the derived
      metrics depend on the orientation of the sample, and are affected by the
      interplay of sampling directions and compartment orientation dispersion when
      applied to macroscopically anisotropic systems. Here we propose a new framework,
      the d-PFG 5-design, to enable rotationally invariant estimation of double wave
      vector diffusion metrics (d-PFG). The method is based on the idea that an
      appropriate orientational average of the signal emulates the signal from a powder
      preparation of the same sample, where macroscopic anisotropy is absent by
      construction. Our approach exploits the theory of exact numerical integration
      (quadrature) of polynomials on the rotation group, and we exemplify the general
      procedure with a set consisting of 60 pairs of diffusion wave vectors (the d-PFG
      5-design) facilitating a theoretically exact determination of the fourth order
      Taylor or cumulant expansion of the orientationally averaged signal. The d-PFG 5
      design is evaluated with numerical simulations and ex vivo high field diffusion
      MRI experiments in a nonhuman primate brain. Specifically, we demonstrate
      rotational invariance when estimating compartment eccentricity, which we show
      offers new microstructural information, complementary to that of fractional
      anisotropy (FA) from diffusion tensor imaging (DTI). The imaging observations are
      supported by a new theoretical result, directly relating compartment eccentricity
      to FA of individual pores.

PMID- 24038643
TI  - A framework for understanding medical epistemologies.
AB  - What clinicians, biomedical scientists, and other health care professionals know
      as individuals or as groups and how they come to know and use knowledge are
      central concerns of medical epistemology. Activities associated with knowledge
      production and use are called epistemic practices. Such practices are considered
      in biomedical and clinical literatures, social sciences of medicine, philosophy
      of science and philosophy of medicine, and also in other nonmedical literatures.
      A host of different kinds of knowledge claims have been identified, each with
      different uses and logics of justification. A general framework is needed to
      situate these diverse contributions in medical epistemology, so we can see how
      they fit together. But developing such a framework turns out to be quite tricky.
      In this survey, three possible frameworks are considered along with the
      difficulties associated with each of them. The essay concludes with a fourth
      framework, which considers any epistemology as part of a practice that is
      oriented toward overcoming errors that emerge in antecedently given practices
      where knowledge is developed and used. As medicine indirectly advances health by
      directly mitigating disease, so epistemology indirectly advances knowledge by
      directly mitigating error. 

PMID- 24038651
TI  - Putting the cenH3 in the centromere: Arabidopsis kinetochore null2 acts upstream
      of cenH3 deposition.

PMID- 24038649
TI  - Intrinsic disorder in pathogen effectors: protein flexibility as an evolutionary
      hallmark in a molecular arms race.
AB  - Effector proteins represent a refined mechanism of bacterial pathogens to
      overcome plants' innate immune systems. These modular proteins often manipulate
      host physiology by directly interfering with immune signaling of plant cells.
      Even if host cells have developed efficient strategies to perceive the presence
      of pathogenic microbes and to recognize intracellular effector activity, it
      remains an open question why only few effectors are recognized directly by plant
      resistance proteins. Based on in-silico genome-wide surveys and a reevaluation of
      published structural data, we estimated that bacterial effectors of
      phytopathogens are highly enriched in long-disordered regions (>50 residues).
      These structurally flexible segments have no secondary structure under
      physiological conditions but can fold in a stimulus-dependent manner (e.g.,
      during protein-protein interactions). The high abundance of intrinsic disorder in
      effectors strongly suggests positive evolutionary selection of this structural
      feature and highlights the dynamic nature of these proteins. We postulate that
      such structural flexibility may be essential for (1) effector translocation, (2)
      evasion of the innate immune system, and (3) host function mimicry. The study of
      these dynamical regions will greatly complement current structural approaches to
      understand the molecular mechanisms of these proteins and may help in the
      prediction of new effectors. 

PMID- 24038650
TI  - The Fragaria vesca homolog of suppressor of overexpression of constans1 represses
      flowering and promotes vegetative growth.
AB  - In the annual long-day plant Arabidopsis thaliana, suppressor of overexpression
      of constans1 (SOC1) integrates endogenous and environmental signals to promote
      flowering. We analyzed the function and regulation of the SOC1 homolog (Fragaria
      vesca [Fv] SOC1) in the perennial short-day plant woodland strawberry (Fragaria
      vesca). We found that Fv SOC1 overexpression represses flower initiation under
      inductive short days, whereas its silencing causes continuous flowering in both
      short days and noninductive long days, similar to mutants in the floral repressor
      Fv terminal flower1 (Fv TFL1). Molecular analysis of these transgenic lines
      revealed that Fv SOC1 activates Fv TFL1 in the shoot apex, leading to the
      repression of flowering in strawberry. In parallel, Fv SOC1 regulates the
      differentiation of axillary buds to runners or axillary leaf rosettes, probably
      through the activation of gibberellin biosynthetic genes. We also demonstrated
      that Fv SOC1 is regulated by photoperiod and Fv flowering locus T1, suggesting
      that it plays a central role in the photoperiodic control of both generative and
      vegetative growth in strawberry. In conclusion, we propose that Fv SOC1 is a
      signaling hub that regulates yearly cycles of vegetative and generative
      development through separate genetic pathways.

PMID- 24038652
TI  - Temporal-spatial interaction between reactive oxygen species and abscisic acid
      regulates rapid systemic acclimation in plants.
AB  - Being sessile organisms, plants evolved sophisticated acclimation mechanisms to
      cope with abiotic challenges in their environment. These are activated at the
      initial site of exposure to stress, as well as in systemic tissues that have not
      been subjected to stress (termed systemic acquired acclimation [SAA]). Although
      SAA is thought to play a key role in plant survival during stress, little is
      known about the signaling mechanisms underlying it. Here, we report that SAA in
      plants requires at least two different signals: an autopropagating wave of
      reactive oxygen species (ROS) that rapidly spreads from the initial site of
      exposure to the entire plant and a stress-specific signal that conveys abiotic
      stress specificity. We further demonstrate that SAA is stress specific and that a
      temporal-spatial interaction between ROS and abscisic acid regulates rapid SAA to
      heat stress in plants. In addition, we demonstrate that the rapid ROS signal is
      associated with the propagation of electric signals in Arabidopsis thaliana. Our
      findings unravel some of the basic signaling mechanisms underlying SAA in plants
      and reveal that signaling events and transcriptome and metabolome reprogramming
      of systemic tissues in response to abiotic stress occur at a much faster rate
      than previously envisioned. 

PMID- 24038654
TI  - Wearing my heart on my chest: dating, new relationships, and the reconfiguration
      of self-esteem after breast cancer.
AB  - OBJECTIVE: This study investigated women's experiences of establishing an
      intimate relationship with a new partner after breast cancer diagnosis and
      treatment. METHODS: Fifteen breast cancer survivors, who were either actively
      dating or in a new intimate relationship that began post-diagnosis, participated
      in semi-structured interviews. Interview transcripts were analyzed using the
      grounded theory method. RESULTS: The analysis yielded Wearing My Heart on My
      Chest as the core category with three underlying categories: (1) Losing and
      Regaining Self and Bodily Esteem; (2) Taking the Leap: Dating and the Obligation
      to Disclose; and (3) Reclaiming of Self through the New Relationship. The
      categories refer to the experience of profound vulnerability invoked by the
      history of breast cancer and the act of verbally and physically revealing this
      past to a new intimate partner. Disclosure entailed a series of successive
      'tests' of the new partner for his ability to accept the physical and
      psychological ramifications of breast cancer, with the resulting relationship
      becoming a vehicle through which women regained self-esteem. CONCLUSIONS: The
      process of dating and starting a new intimate relationship had the potential to
      restore women's self and bodily esteem previously diminished by breast cancer.
      The reconfiguration of self-esteem following breast cancer is thus experienced as
      an ongoing process that begins with diagnosis and continues well into the new
      relationship.

PMID- 24038655
TI  - Cross-coupling reaction of a highly strained molecule: synthesis of sigma-pi
      conjugated tetrahedranes.

PMID- 24038653
TI  - TED, an autonomous and rare maize transposon of the mutator superfamily with a
      high gametophytic excision frequency.
AB  - Mutator (Mu) elements, one of the most diverse superfamilies of DNA transposons,
      are found in all eukaryotic kingdoms, but are particularly numerous in plants.
      Most of the present knowledge on the transposition behavior of this superfamily
      comes from studies of the maize (Zea mays) Mu elements, whose transposition is
      mediated by the autonomous Mutator-Don Robertson (MuDR) element. Here, we
      describe the maize element TED (for Transposon Ellen Dempsey), an autonomous
      cousin that differs significantly from MuDR. Element excision and reinsertion
      appear to require both proteins encoded by MuDR, but only the single protein
      encoded by TED. Germinal excisions, rare with MuDR, are common with TED, but
      arise in one of the mitotic divisions of the gametophyte, rather than at meiosis.
      Instead, transposition-deficient elements arise at meiosis, suggesting that the
      double-strand breaks produced by element excision are repaired differently in
      mitosis and meiosis. Unlike MuDR, TED is a very low-copy transposon whose number
      and activity do not undergo dramatic changes upon inbreeding or outcrossing. Like
      MuDR, TED transposes mostly to unlinked sites and can form circular transposition
      products. Sequences closer to TED than to MuDR were detected only in the grasses,
      suggesting a rather recent evolutionary split from a common ancestor. 

PMID- 24038657
TI  - Imidazole-nitrile or imidazole-isonitrile C-C coupling on rhenium tricarbonyl
      complexes.
AB  - Ligand activation: Deprotonation of the nitrile or isonitrile complexes
      [Re(CO)3(N-RIm)2(L)](+) (N-RIm = N-alkylimidazole; L = N=CtBu, C=NtBu)
      selectively afforded alkylidenamido or iminoacyl derivatives, respectively, in
      which C-C coupling has occurred. Protonation of the latter complex leads to
      aminocarbene products.

PMID- 24038656
TI  - Arimetamycin A: improving clinically relevant families of natural products
      through sequence-guided screening of soil metagenomes.
AB  - Sequence-tag-guided screening of soil environmental DNA libraries can be used to
      guide the discovery of new compounds with improved properties. In heterologous
      expression experiments the eDNA-derived arm cluster encodes arimetamycin A, an
      anthracycline that is more potent than clinically used natural anthracyclines and
      retains activity against multidrug-resistant (MDR) cancer cells. 

PMID- 24038658
TI  - Contamination of the surgical field in head and neck oncologic surgery.
AB  - BACKGROUND: The purpose of this study was to determine the timing and type of
      surgical field contamination in 50 consecutive resections for advanced head and
      neck cancer with same-stage tissue reconstruction and to analyze the relationship
      between contamination and the surgical site infection. METHODS: Swabs from the
      surgical field and from surgical drapes close to the field were taken every 2
      hours (at 0 hour, 2 hours, 4 hours, and 6 hours) and sent for a standard
      microbiological diagnostic procedure. Results were recorded in Microsoft Excel
      and analyzed with SPSS. RESULTS: We collected 336 swabs of which 71% were
      contaminated. Polymicrobial contamination was observed in 153 samples (45%).
      Twenty-six species of pathogens were found, the most frequent was Streptococcus
      species. Surgical site infection with positive culture occurred in 3 patients.
      CONCLUSION: In head and neck surgery for advanced cancer, standard aseptic
      procedures do not prevent contamination of the surgical field with physiological
      bacterial flora of the skin and oral cavity. Although contamination was common,
      surgical site infection was rare.

PMID- 24038659
TI  - Insights into the evolution of lanthipeptide biosynthesis.
AB  - Lanthipeptides are a group of posttranslationally modified peptide natural
      products that contain multiple thioether crosslinks. These crosslinks are formed
      by dehydration of Ser/Thr residues followed by addition of the thiols of Cys
      residues to the resulting dehydroamino acids. At least four different pathways to
      these polycyclic natural products have evolved, reflecting the high efficiency
      and evolvability of a posttranslational modification route to generate
      conformationally constrained peptides. The wealth of genomic information that has
      been made available in recent years has started to provide insights into how
      these remarkable pathways and their posttranslational modification machineries
      may have evolved. In this review, we discuss a model for the evolution of the
      lanthipeptide biosynthetic enzymes that has recently been developed based on the
      currently available data. 

PMID- 24038660
TI  - A high Notch pathway activation predicts response to gamma secretase inhibitors
      in proneural subtype of glioma tumor-initiating cells.
AB  - Genomic, transcriptional, and proteomic analyses of brain tumors reveal subtypes
      that differ in pathway activity, progression, and response to therapy. However, a
      number of small molecule inhibitors under development vary in strength of subset
      and pathway-specificity, with molecularly targeted experimental agents tending
      toward stronger specificity. The Notch signaling pathway is an evolutionarily
      conserved pathway that plays an important role in multiple cellular and
      developmental processes. We investigated the effects of Notch pathway inhibition
      in glioma tumor-initiating cell (GIC, hereafter GIC) populations using gamma
      secretase inhibitors. Drug cytotoxicity testing of 16 GICs showed differential
      growth responses to the inhibitors, stratifying GICs into responders and
      nonresponders. Responder GICs had an enriched proneural gene signature in
      comparison to nonresponders. Also gene set enrichment analysis revealed 17 genes
      set representing active Notch signaling components NOTCH1, NOTCH3, HES1, MAML1,
      DLL-3, JAG2, and so on, enriched in responder group. Analysis of The Cancer
      Genome Atlas expression dataset identified a group (43.9%) of tumors with
      proneural signature showing high Notch pathway activation suggesting gamma
      secretase inhibitors might be of potential value to treat that particular group
      of proneural glioblastoma (GBM). Inhibition of Notch pathway by gamma secretase
      inhibitor treatment attenuated proliferation and self-renewal of responder GICs
      and induces both neuronal and astrocytic differentiation. In vivo evaluation
      demonstrated prolongation of median survival in an intracranial mouse model. Our
      results suggest that proneural GBM characterized by high Notch pathway activation
      may exhibit greater sensitivity to gamma secretase inhibitor treatment, holding a
      promise to improve the efficiency of current glioma therapy.

PMID- 24038662
TI  - Modularity analysis of tunable solid-state emission based on a twisted conjugated
      molecule containing 9,9'-bianthracene group.
AB  - The solid-state luminescence behavior of a compound (BAPN) depends on the
      molecular aggregation pattern. Modular analysis shows that the two emitting
      systems within the BAPN molecule are responsible for switching the emission color
      in various aggregation states. 

PMID- 24038661
TI  - Increased longevity mediated by yeast NDI1 expression in Drosophila intestinal
      stem and progenitor cells.
AB  - A functional decline in tissue stem cells and mitochondrial dysfunction have each
      been linked to aging and multiple aging-associated pathologies. However, the
      interplay between energy homeostasis, stem cells, and organismal aging remains
      poorly understood. Here, we report that expression of the single-subunit yeast
      alternative NADH dehydrogenase, ndi1, in Drosophila intestinal stem and
      progenitor cells delays the onset of multiple markers of intestinal aging and
      extends lifespan. In addition, expression of ndi1 in the intestine increases
      feeding behavior and results in organismal weight gain. Consistent with increased
      nutrient uptake, flies expressing ndi1 in the digestive tract display a systemic
      reduction in the activity of AMP-activated protein kinase (AMPK), a key cellular
      energy sensor. Together, these results demonstrate that ndi1 expression in the
      intestinal epithelium is an effective strategy to delay tissue and organismal
      aging.

PMID- 24038663
TI  - Functionalization of benzylic C(sp(3))-H bonds of heteroaryl aldehydes through N
      heterocyclic carbene organocatalysis.
AB  - Aryl aldehyde activation: Oxidative activation of 2-methylindole-3-carboxaldehyde
      (I) through N-heterocyclic carbene (NHC) organocatalysis generates heterocyclic
      ortho-quinodimethane (II) as a key intermediate. This intermediate then undergoes
      formal [4+2] cycloaddition with trifluoromethyl ketones or isatins to form
      polycyclic lactones containing a quaternary carbon center. 

PMID- 24038664
TI  - Organocatalytic triazole formation, followed by oxidative aromatization:
      regioselective metal-free synthesis of benzotriazoles.
AB  - Herein we report on our studies on the sequential one-pot combinations of amine
      catalyzed multicomponent reactions (MCRs). We have developed the copper-free
      synthesis of functionalized bicyclic N-aryl-1,2,3-triazole and N
      arylbenzotriazole products 4 and 5 from the simple unmodified starting materials
      through [3+2]-cycloaddition ([3+2]-CA) and oxidative aromatization reactions in
      one pot under amine catalysis. The sequential one-pot reaction proceeds in good
      yields with high selectivity by using pyrrolidine as the catalyst from the simple
      unmodified substrates of enones, aryl azides, and 2,3-dichloro-5,6-dicyano-1,4
      benzoquinone (DDQ). Furthermore, we have demonstrated the medicinal applications
      of products 4 and 5 through simple organic reactions. 

PMID- 24038665
TI  - Environmental regulation of plant gene expression: an RT-qPCR laboratory project
      for an upper-level undergraduate biochemistry or molecular biology course.
AB  - We present a novel laboratory project employing "real-time" RT-qPCR to measure
      the effect of environment on the expression of the FLOWERING LOCUS C gene, a key
      regulator of floral timing in Arabidopsis thaliana plants. The project requires
      four 3-hr laboratory sessions and is aimed at upper-level undergraduate students
      in biochemistry or molecular biology courses. The project provides students with
      hands-on experience with RT-qPCR, the current "gold standard" for gene expression
      analysis, including detailed data analysis using the common 2-DeltaDeltaCT
      method. Moreover, it provides a convenient starting point for many inquiry-driven
      projects addressing diverse questions concerning ecological biochemistry,
      naturally occurring genetic variation, developmental biology, and the regulation
      of gene expression in nature.

PMID- 24038666
TI  - Formation of trichlorosilyl-substituted carbon-centered stable radicals through
      the use of pi-accepting carbenes.

PMID- 24038667
TI  - Gray and white matter correlates of navigational ability in humans.
AB  - Humans differ widely in their navigational abilities. Studies have shown that
      self-reports on navigational abilities are good predictors of performance on
      navigation tasks in real and virtual environments. The caudate nucleus and medial
      temporal lobe regions have been suggested to subserve different navigational
      strategies. The ability to use different strategies might underlie navigational
      ability differences. This study examines the anatomical correlates of self
      reported navigational ability in both gray and white matter. Local gray matter
      volume was compared between a group (N = 134) of good and bad navigators using
      voxel-based morphometry (VBM), as well as regional volumes. To compare between
      good and bad navigators, we also measured white matter anatomy using diffusion
      tensor imaging (DTI) and looked at fractional anisotropy (FA) values. We observed
      a trend toward higher local GM volume in right anterior parahippocampal/rhinal
      cortex for good versus bad navigators. Good male navigators showed significantly
      higher local GM volume in right hippocampus than bad male navigators. Conversely,
      bad navigators showed increased FA values in the internal capsule, the white
      matter bundle closest to the caudate nucleus and a trend toward higher local GM
      volume in the caudate nucleus. Furthermore, caudate nucleus regional volume
      correlated negatively with navigational ability. These convergent findings across
      imaging modalities are in line with findings showing that the caudate nucleus and
      the medial temporal lobes are involved in different wayfinding strategies. Our
      study is the first to show a link between self-reported large-scale navigational
      abilities and different measures of brain anatomy.

PMID- 24038668
TI  - Generic substitution does not seem to affect adherence negatively in elderly
      polypharmacy patients.
AB  - PURPOSE: To investigate the association between generic substitutions and
      medication adherence in elderly patients with prescribed polypharmacy. METHODS:
      Our study included 672 patients aged 65+ years, living at home in the
      municipality of Aarhus (Denmark), who at the time of enrolment took at least five
      prescription drugs daily including both short-term and long-term treatment
      independently of kind of administration route but without assistance. In this
      paper, only oral drugs for long-term treatment are included in the analysis
      resulting in median of three drugs per patient. Adherence was assessed by pill
      counts. Patients with a mean adherence rate <80% across all oral drugs consumed
      for long-term treatment were categorised as non-adherent. The number of generic
      substitutions during 1 year was retrieved from the National Health Insurance
      prescription database. Each change in either a drug's or a manufacturer's name
      was regarded as a substitution. The association between generic substitution and
      the mean adherence rate to all drugs was analysed by contingency table analyses
      and a trend test. RESULTS: During 1 year, at least one substitution was
      experienced by 83.6% of patients (n = 562). Patients non-adherent to long-term
      oral treatment (n = 46) amounted to 8% of all patients who experienced
      substitutions. Amongst 110 elderly patients (16.4%) who did not experience
      substitutions, 16% were non-adherent (odds ratio 0.46; 95% confidence interval
      0.25-0.82). CONCLUSION: As generic substitution in elderly patients undergoing
      polypharmacy appears not to affect adherence to long-term drug treatment
      negatively, there seems to be no obvious reason for avoiding generic substitution
      in such patients.

PMID- 24038669
TI  - Energy allocation between brain and body during ontogenetic development.
AB  - OBJECTIVE: We here studied how energy is allocated between brain and body both
      during the ontogenetic development from a child to an adult and during weight
      loss. METHODS: We investigated 180 normal weight female and male children and
      adolescents (aged 6.1-19.9 years) as well as 35 overweight adolescents undergoing
      weight reduction intervention. 52 normal weight and 42 obese adult women were
      used for comparison. We assessed brain mass by magnetic-resonance-imaging and
      body metabolism by indirect calorimetry. To study how energy is allocated between
      brain and body, we measured plasma insulin, since insulin fulfils the functions
      of a glucose allocating hormone, i.e., peripheral glucose uptake depends on
      insulin, central uptake does not. We used reference data obtained in the field of
      comparative biology. In a brain-body-plot, we calculated the distance between
      each subject and a reference mammal of comparable size and named the distance
      "encephalic measure." With higher encephalic measures, more energy is allocated
      to the brain. RESULTS: We found that ontogenetic development from a child to an
      adult was indicated by decreasing encephalic measures in females (r = -0.729, P <
      0.001) and increasing plasma insulin concentrations (F = 6.6, P = 0.002 in
      females and F = 8.6, P < 0.001 in males). Weight loss of about 5 kg in females
      and about 9 kg in males resulted in reduced insulin concentrations and increased
      encephalic measures. CONCLUSION: Our results indicate that the share of energy
      allocated to the brain increased with weight loss, but decreased during the
      ontogenetic development from childhood to adolescence. These developmental
      changes in brain-to-body energy allocation appear to be driven by increasing
      plasma insulin concentrations.

PMID- 24038670
TI  - Q-ball imaging with PROPELLER EPI acquisition.
AB  - Q-ball imaging (QBI) is an imaging technique that is capable of resolving
      intravoxel fiber crossings; however, the signal readout based on echo-planar
      imaging (EPI) introduces geometric distortions in the presence of susceptibility
      gradients. This study proposes an imaging technique that reduces susceptibility
      distortions in QBI by short-axis PROPELLER EPI acquisition. Conventional QBI and
      PROPELLER QBI data were acquired from two 3T MR scans of the brains of five
      healthy subjects. Prior to the PROPELLER reconstruction, residual distortions in
      single-blade low-resolution b0 and diffusion-weighted images (DWIs) were
      minimized by linear affine and nonlinear diffeomorphic demon registrations.
      Subsequently, the PROPELLER keyhole reconstruction was applied to the corrected
      DWIs to obtain high-resolution PROPELLER DWIs. The generalized fractional
      anisotropy and orientation distribution function maps contained fewer distortions
      in PROPELLER QBI than in conventional QBI, and the fiber tracts more closely
      matched the brain anatomy depicted by turbo spin-echo (TSE) T2-weighted imaging
      (T2WI). Furthermore, for fixed T(E), PROPELLER QBI enabled a shorter scan time
      than conventional QBI. We conclude that PROPELLER QBI can reduce susceptibility
      distortions without lengthening the acquisition time and is suitable for tracing
      neuronal fiber tracts in the human brain.

PMID- 24038671
TI  - The crystal structure of human quinolinic acid phosphoribosyltransferase in
      complex with its inhibitor phthalic acid.
AB  - Quinolinic acid (QA), a biologically potent but neurodestructive metabolite is
      catabolized by quinolinic acid phosphoribosyltransferase (QPRT) in the first step
      of the de novo NAD(+) biosynthesis pathway. This puts QPRT at the junction of two
      different pathways, that is, de novo NAD(+) biosynthesis and the kynurenine
      pathway of tryptophan degradation. Thus, QPRT is an important enzyme in terms of
      its biological impact and its potential as a therapeutic target. Here, we report
      the crystal structure of human QPRT bound to its inhibitor phthalic acid (PHT)
      and kinetic analysis of PHT inhibition of human QPRT. This structure, determined
      at 2.55 A resolution, shows an elaborate hydrogen bonding network that helps in
      recognition of PHT and consequently its substrate QA. In addition to this
      hydrogen bonding network, we observe extensive van der Waals contacts with the
      PHT ring that might be important for correctly orientating the substrate QA
      during catalysis. Moreover, our crystal form allows us to observe an intact
      hexamer in both the apo- and PHT-bound forms in the same crystal system, which
      provides a direct comparison of unique subunit interfaces formed in hexameric
      human QPRT. We call these interfaces "nondimeric interfaces" to distinguish them
      from the typical dimeric interfaces observed in all QPRTs. We observe significant
      changes in the nondimeric interfaces in the QPRT hexamer upon binding PHT. Thus,
      the new structural and functional features of this enzyme we describe here will
      aid in understanding the function of hexameric QPRTs, which includes all
      eukaryotic and select prokaryotic QPRTs.

PMID- 24038672
TI  - In silico design of heteroaromatic half-sandwich RhI catalysts for acetylene
      [2+2+2] cyclotrimerization: evidence of a reverse indenyl effect.
AB  - A mechanistic density functional theory study of acetylene [2+2+2]
      cyclotrimerization to benzene catalyzed by Rh(I) half metallocenes is presented.
      The catalyst fragment contains a heteroaromatic ligand, that is, the 1,2
      azaborolyl (Ab) or the 3a,7a-azaborindenyl (Abi) anions, which are isostructural
      and isoelectronic to the hydrocarbon cyclopentadienyl (Cp) and indenyl (Ind)
      anions, respectively, but differ from the last ones on having two adjacent carbon
      atoms replaced with a boron and a nitrogen atom. The better performance of either
      the classic hydrocarbon or the heteroaromatic catalysts is found to depend on the
      different mechanistic paths that can be envisioned for the process. The present
      analyses uncover and explain general structure-reactivity relationships that may
      serve as rational design principles. In particular, we provide evidence of a
      reverse indenyl effect. 

PMID- 24038673
TI  - Manipulating liquid-crystal properties using a pH activated hydrazone switch.

PMID- 24038674
TI  - Release and recovery of guest molecules during the reversible borate gel
      formation of guest-included macrocyclic boronic esters.
AB  - Borate gel formation from guest-encapsulated macrocyclic boronic esters was
      realized by the addition of a diamine to the suspension of the boronic esters in
      various organic solvents, which triggered the release of the guest compounds. The
      guest molecules could be recovered from the borate gel by addition of an acid to
      remove the diamine, which facilitated the reconstruction of the initial guest
      encapsulated macrocyclic boronic esters. 

PMID- 24038675
TI  - Spectroscopic and electrochemical characterization of the [NiFeSe] hydrogenase
      from Desulfovibrio vulgaris Miyazaki F: reversible redox behavior and
      interactions between electron transfer centers.
AB  - Characterizing a new hydrogenase: The newly isolated [NiFeSe] hydrogenase from
      Desulfovibrio vulgaris Miyazaki F displays catalytic properties distinct from
      other hydrogenase proteins. Here we apply site-specific spectroscopic and
      electrochemical techniques to characterize these unique features at the molecular
      level. 

PMID- 24038676
TI  - Electrografting of diazonium-functionalized polyoxometalates: synthesis,
      immobilisation and electron-transfer characterisation from glassy carbon.
AB  - Polyoxometalates (POMs) are attractive candidates for the rational design of
      multi-level charge-storage materials because they display reversible multi-step
      reduction processes in a narrow range of potentials. The functionalization of
      POMs allows for their integration in hybrid complementary metal oxide
      semiconductor (CMOS)/molecular devices, provided that fine control of their
      immobilisation on various substrates can be achieved. Owing to the wide
      applicability of the diazonium route to surface modification, a functionalized
      Keggin-type POM [PW11 O39 {Ge(p-C6 H4 -C?C-C6 H4 -${{?rm N}{{+?hfill ?atop
      2?hfill}}}$)}](3-) bearing a pending diazonium group was prepared and
      subsequently covalently anchored onto a glassy carbon electrode. Electron
      transfer with the immobilised POM was thoroughly investigated and compared to
      that of the free POM in solution. 

PMID- 24038677
TI  - Dehydrogenative coupling to enable the enantioselective total synthesis of (-)
      simaomicin alpha.

PMID- 24038678
TI  - Brief report: reconstruction of joint hyaline cartilage by autologous progenitor
      cells derived from ear elastic cartilage.
AB  - In healthy joints, hyaline cartilage covering the joint surfaces of bones
      provides cushioning due to its unique mechanical properties. However, because of
      its limited regenerative capacity, age- and sports-related injuries to this
      tissue may lead to degenerative arthropathies, prompting researchers to
      investigate a variety of cell sources. We recently succeeded in isolating human
      cartilage progenitor cells from ear elastic cartilage. Human cartilage progenitor
      cells have high chondrogenic and proliferative potential to form elastic
      cartilage with long-term tissue maintenance. However, it is unknown whether ear
      derived cartilage progenitor cells can be used to reconstruct hyaline cartilage,
      which has different mechanical and histological properties from elastic
      cartilage. In our efforts to develop foundational technologies for joint hyaline
      cartilage repair and reconstruction, we conducted this study to obtain an answer
      to this question. We created an experimental canine model of knee joint cartilage
      damage, transplanted ear-derived autologous cartilage progenitor cells. The
      reconstructed cartilage was rich in proteoglycans and showed unique histological
      characteristics similar to joint hyaline cartilage. In addition, mechanical
      properties of the reconstructed tissues were higher than those of ear cartilage
      and equal to those of joint hyaline cartilage. This study suggested that joint
      hyaline cartilage was reconstructed from ear-derived cartilage progenitor cells.
      It also demonstrated that ear-derived cartilage progenitor cells, which can be
      harvested by a minimally invasive method, would be useful for reconstructing
      joint hyaline cartilage in patients with degenerative arthropathies.

PMID- 24038679
TI  - The REIL1 and REIL2 proteins of Arabidopsis thaliana are required for leaf growth
      in the cold.
AB  - The evolutionarily conserved proteins REI1-LIKE (REIL1) and REIL2 have four
      conserved zinc finger domains and are Arabidopsis thaliana homologs of the
      cytosolic 60S ribosomal maturation factor Rei1p (for Required for isotropic bud
      growth1 protein) from yeast (Saccharomyces cerevisiae) and its paralog Reh1p (for
      REI1 homologue1 protein). The yeast and A. thaliana paralogs result from
      independent gene duplications. The A. thaliana REIL paralogs are required
      specifically in the cold (10 degrees C) but not for growth at optimal temperature
      (20 degrees C). A reil1-1 reil2-1 double mutant is arrested at 10 degrees C prior
      to the emergence of the first rosette leaf. Two allelic reil2 mutants, reil2-1
      and reil2-2, form small spoon-shaped leaves at 10 degrees C. This phenomenon
      reverts after emergence of the inflorescence in the cold or upon shift to 20
      degrees C. Except for a slightly delayed germination, a reil1-1 mutant shows no
      further growth phenotype under the currently investigated conditions. A
      comparative analysis demonstrates conserved coexpression of orthologous genes
      from yeast and A. thaliana that are coregulated with yeast rei1 or with A.
      thaliana REIL2, respectively. The conserved correlations point to a role of A.
      thaliana REIL proteins in the maturation of the eukaryotic ribosomal 60S subunit.
      We support this conclusion by heterologous complementation of the cold-induced
      growth defect of the yeast Deltarei1 deletion. 

PMID- 24038680
TI  - Role of filamentous phage SW1 in regulating the lateral flagella of Shewanella
      piezotolerans strain WP3 at low temperatures.
AB  - Low-temperature ecosystems represent the largest biosphere on Earth, and yet our
      understanding of the roles of bacteriophages in these systems is limited. Here,
      the influence of the cold-active filamentous phage SW1 on the phenotype and gene
      transcription of its host, Shewanella piezotolerans WP3 (WP3), was investigated
      by construction of a phage-free strain (WP3DeltaSW1), which was compared with the
      wild-type strain. The expression of 49 genes, including 16 lateral flagellar
      genes, was found to be significantly influenced by SW1 at 4 degrees C, as
      demonstrated by comparative whole-genome microarray analysis. WP3DeltaSW1 was
      shown to have a higher production of lateral flagella than WP3 and enhanced
      swarming motility when cultivated on solid agar plates. Besides, SW1 has a
      remarkable impact on the expression of a variety of host genes in liquid culture,
      particularly the genes related to the membrane and to the production of lateral
      flagella. These results suggest that the deep-sea bacterium WP3 might balance the
      high-energy demands of phage maintenance and swarming motility at low
      temperatures. The phage SW1 is shown to have a significant influence on the
      swarming ability of the host and thus may play an important role in adjusting the
      fitness of the cells in the deep-sea environment. 

PMID- 24038681
TI  - Characterization of CpdC, a large-ring lactone-hydrolyzing enzyme from
      Pseudomonas sp. strain HI-70, and its use as a fusion tag facilitating
      overproduction of proteins in Escherichia coli.
AB  - There are few entries of carbon-carbon bond hydrolases (EC 3.7.1.-) in the ExPASy
      database. In microbes, these enzymes play an essential role in the metabolism of
      alicyclic or aromatic compounds as part of the global carbon cycle. CpdC is a
      omega-pentadecalactone hydrolase derived from the degradation pathway of
      cyclopentadecanol or cyclopentadecanone by Pseudomonas sp. strain HI-70. CpdC was
      purified to homogeneity and characterized. It is active as a dimer of 56,000 Da
      with a subunit molecular mass of 33,349. Although CpdC has the highest activity
      and reaction rate (kcat) toward omega-pentadecalactone, its catalytic efficiency
      favors lauryl lactone as a substrate. The melting temperature (Tm) of CpdC was
      estimated to be 50.9 +/- 0.1 degrees C. The half-life of CpdC at 35 degrees C is
      several days. By virtue of its high level of expression in Escherichia coli, the
      intact CpdC-encoding gene and progressive 3'-end deletions were employed in the
      construction of a series of fusion plasmid system. Although we found them in
      inclusion bodies, proof-of-concept of overproduction of three microbial cutinases
      of which the genes were otherwise expressed poorly or not at all in E. coli was
      demonstrated. On the other hand, two antigenic proteins, azurin and MPT63, were
      readily produced in soluble form. 

PMID- 24038683
TI  - Characteristics of cefotaxime-resistant Escherichia coli from wild birds in the
      Netherlands.
AB  - Cloacal swabs from carcasses of Dutch wild birds obtained in 2010 and 2011 were
      selectively cultured on media with cefotaxime to screen for the presence of
      extended-spectrum beta-lactamase (ESBL)/AmpC-producing Escherichia coli.
      Subsequently, all cefotaxime-resistant E. coli isolates were tested by broth
      microdilution and microarray. The presence of ESBL/AmpC and coexisting plasmid
      mediated quinolone resistance (PMQR) genes was confirmed by PCR and sequencing.
      To determine the size of plasmids and the location of ESBL and PMQR genes, S1
      pulsed-field gel electrophoresis (PFGE) was performed on transformants, followed
      by Southern blot hybridization. The study included 414 cloacal swabs originating
      from 55 different bird species. Cefotaxime-resistant E. coli isolates were
      identified in 65 birds (15.7%) from 21 different species. In all, 65 cefotaxime
      resistant E. coli ESBL/AmpC genes were detected, mainly comprising variants of
      blaCTX-M and blaCMY-2. Furthermore, PMQR genes [aac(6')-lb-cr, qnrB1, and qnrS1]
      coincided in seven cefotaxime-resistant E. coli isolates. Overall, replicon
      typing of the ESBL/AmpC-carrying plasmids demonstrated the predominant presence
      of IncI1 (n = 31) and variants of IncF (n = 18). Our results indicate a wide
      dissemination of ESBL and AmpC genes in wild birds from The Netherlands,
      especially among aquatic-associated species (waterfowl, gulls, and waders). The
      identified genes and plasmids reflect the genes found predominantly in livestock
      animals as well as in humans. 

PMID- 24038682
TI  - Analysis of genes for succinoyl trehalose lipid production and increasing
      production in Rhodococcus sp. strain SD-74.
AB  - Succinoyl trehalose lipids (STLs) are promising glycolipid biosurfactants
      produced from n-alkanes that are secreted by Rhodococcus species bacteria. These
      compounds not only exhibit unique interfacial properties but also demonstrate
      versatile biochemical actions. In this study, three novel types of genes involved
      in the biosynthesis of STLs, including a putative acyl coenzyme A (acyl-CoA)
      transferase (tlsA), fructose-bisphosphate aldolase (fda), and alkane
      monooxygenase (alkB), were identified. The predicted functions of these genes
      indicate that alkane metabolism, sugar synthesis, and the addition of acyl groups
      are important for the biosynthesis of STLs. Based on these results, we propose a
      biosynthesis pathway for STLs from alkanes in Rhodococcus sp. strain SD-74. By
      overexpressing tlsA, we achieved a 2-fold increase in the production of STLs.
      This study advances our understanding of bacterial glycolipid production in
      Rhodococcus species. 

PMID- 24038684
TI  - Bacterial persister cell formation and dormancy.
AB  - Bacterial cells may escape the effects of antibiotics without undergoing genetic
      change; these cells are known as persisters. Unlike resistant cells that grow in
      the presence of antibiotics, persister cells do not grow in the presence of
      antibiotics. These persister cells are a small fraction of exponentially growing
      cells (due to carryover from the inoculum) but become a significant fraction in
      the stationary phase and in biofilms (up to 1%). Critically, persister cells may
      be a major cause of chronic infections. The mechanism of persister cell formation
      is not well understood, and even the metabolic state of these cells is debated.
      Here, we review studies relevant to the formation of persister cells and their
      metabolic state and conclude that the best model for persister cells is still
      dormancy, with the latest mechanistic studies shedding light on how cells reach
      this dormant state. 

PMID- 24038685
TI  - Enhanced biotransformation of fluoranthene by intertidally derived Cunninghamella
      elegans under biofilm-based and niche-mimicking conditions.
AB  - The aims of the investigation were to ascertain if surface attachment of
      Cunninghamella elegans and niche intertidal conditions provided in a bioreactor
      influenced biotransformation of fluoranthene by C. elegans. A newly designed
      polymethylmethacrylate (PMMA) conico-cylindrical flask (CCF) holding eight
      equidistantly spaced rectangular strips mounted radially on a circular disc
      allowed comparison of fluoranthene biotransformation between CCFs with a
      hydrophobic surface (PMMA-CCF) and a hydrophilic glass surface (GS-CCF) and a 500
      ml Erlenmeyer flask (EF). Fluoranthene biotransformation was higher by 22-fold,
      biofilm growth was higher by 3-fold, and cytochrome P450 gene expression was
      higher by 2.1-fold when C. elegans was cultivated with 2% inoculum as biofilm
      culture in PMMA-CCF compared to planktonic culture in EF. Biotransformation was
      enhanced by 7-fold with 10% inoculum. The temporal pattern of biofilm progression
      based on three-channel fluorescence detection by confocal laser scanning
      microscopy demonstrated well-developed, stable biofilm with greater
      colocalization of fluoranthene within extracellular polymeric substances and
      filaments of the biofilm grown on PMMA in contrast to a glass surface. A
      bioreactor with discs rotating at 2 revolutions per day affording 6-hourly
      emersion and immersion mimicked the niche intertidal habitat of C. elegans and
      supported biofilm formation and transformation of fluoranthene. The amount of
      transformed metabolite was 3.5-fold, biofilm growth was 3-fold, and cytochrome
      P450 gene expression was 1.9-fold higher in the process mimicking the intertidal
      conditions than in a submerged process without disc rotation. In the CCF and
      reactor, where biofilm formation was comparatively greater, higher concentration
      of exopolysaccharides allowed increased mobilization of fluoranthene within the
      biofilm with consequential higher gene expression leading to enhanced volumetric
      productivity. 

PMID- 24038686
TI  - Bacterial contribution to dissolved organic matter in eutrophic Lake Kasumigaura,
      Japan.
AB  - Incubation experiments using filtered waters from Lake Kasumigaura were conducted
      to examine bacterial contribution to a dissolved organic carbon (DOC) pool.
      Bacterial abundance, bacterial production, concentrations of DOC, total dissolved
      amino acids (TDAA), and total dissolved neutral sugars (TDNS) were monitored
      during the experiments. Bacterial production during the first few days was very
      high (20 to 35 MUg C liter(-1) day(-1)), accounting for 40 to 70% of primary
      production. The total bacterial production accounted for 34 to 55% of the DOC
      loss during the experiment, indicating high bacterial activities in Lake
      Kasumigaura. The DOC degradation was only 12 to 15%, whereas the degradation of
      TDAA and TDNS ranged from 30 to 50%, suggesting the preferential usage of TDAA
      and TDNS. The contribution of bacterially derived carbon to a DOC pool in Lake
      Kasumigaura was estimated using d-amino acids as bacterial biomarkers and
      accounted for 30 to 50% of the lake DOC. These values were much higher than those
      estimated for the open ocean (20 to 30%). The ratio of bacterially derived carbon
      to bulk carbon increased slightly with time, suggesting that the bacterially
      derived carbon is more resistant to microbial degradation than bulk carbon. This
      is the first study to estimate the bacterial contribution to a DOC pool in
      freshwater environments. These results indicate that bacteria play even more
      important roles in carbon cycles in freshwater environments than in open oceans
      and also suggests that recent increases in recalcitrant DOC in various lakes
      could be attributed to bacterially derived carbon. The potential differences in
      bacterial contributions to dissolved organic matter (DOM) between freshwater and
      marine environments are discussed. 

PMID- 24038687
TI  - Influence of habitat and climate variables on arbuscular mycorrhizal fungus
      community distribution, as revealed by a case study of facultative plant
      epiphytism under semiarid conditions.
AB  - In semiarid Mediterranean ecosystems, epiphytic plant species are practically
      absent, and only some species of palm trees can support epiphytes growing in
      their lower crown area, such as Phoenix dactylifera L. (date palm). In this
      study, we focused on Sonchus tenerrimus L. plants growing as facultative
      epiphytes in P. dactylifera and its terrestrial forms growing in adjacent soils.
      Our aim was to determine the possible presence of arbuscular mycorrhizal fungi
      (AMF) in these peculiar habitats and to relate AMF communities with climatic
      variations. We investigated the AMF community composition of epiphytic and
      terrestrial S. tenerrimus plants along a temperature and precipitation gradient
      across 12 localities. Epiphytic roots were colonized by AMF, as determined by
      microscopic observation; all of the epiphytic and terrestrial samples analyzed
      showed AMF sequences from taxa belonging to the phylum Glomeromycota, which were
      grouped in 30 AMF operational taxonomic units. The AMF community composition was
      clearly different between epiphytic and terrestrial root samples, and this could
      be attributable to dispersal constraints and/or the contrasting environmental and
      ecophysiological conditions prevailing in each habitat. Across sites, the
      richness and diversity of terrestrial AMF communities was positively correlated
      with rainfall amount during the most recent growing season. In contrast, there
      was no significant correlation between climate variables and AMF richness and
      diversity for epiphytic AMF communities, which suggests that the composition of
      AMF communities in epiphytic habitats appears to be largely determined by the
      availability and dispersion of fungal propagules from adjacent terrestrial
      habitats. 

PMID- 24038688
TI  - Impacts of labile organic carbon concentration on organic and inorganic nitrogen
      utilization by a stream biofilm bacterial community.
AB  - In aquatic ecosystems, carbon (C) availability strongly influences nitrogen (N)
      dynamics. One manifestation of this linkage is the importance in the dissolved
      organic matter (DOM) pool of dissolved organic nitrogen (DON), which can serve as
      both a C and an N source, yet our knowledge of how specific properties of DOM
      influence N dynamics are limited. To empirically examine the impact of labile DOM
      on the responses of bacteria to DON and dissolved inorganic nitrogen (DIN),
      bacterial abundance and community composition were examined in controlled
      laboratory microcosms subjected to various combinations of dissolved organic
      carbon (DOC), DON, and DIN treatments. Bacterial communities that had colonized
      glass beads incubated in a stream were treated with various glucose
      concentrations and combinations of inorganic and organic N (derived from algal
      exudate, bacterial protein, and humic matter). The results revealed a strong
      influence of C availability on bacterial utilization of DON and DIN, with
      preferential uptake of DON under low C concentrations. Bacterial DON uptake was
      affected by the concentration and by its chemical nature (labile versus
      recalcitrant). Labile organic N sources (algal exudate and bacterial protein)
      were utilized equally well as DIN as an N source, but this was not the case for
      the recalcitrant humic matter DON treatment. Clear differences in bacterial
      community composition among treatments were observed based on terminal
      restriction fragment length polymorphisms (T-RFLP) of 16S rRNA genes. C, DIN, and
      DON treatments likely drove changes in bacterial community composition that in
      turn affected the rates of DON and DIN utilization under various C
      concentrations. 

PMID- 24038689
TI  - Noninvasive high-throughput single-cell analysis of the intracellular pH of
      Saccharomyces cerevisiae by ratiometric flow cytometry.
AB  - The ability of cells to maintain pH homeostasis in response to environmental
      changes has elicited interest in basic and applied research and has prompted the
      development of methods for intracellular pH measurements. Many traditional
      methods provide information at population level and thus the average values of
      the studied cell physiological phenomena, excluding the fact that cell cultures
      are very heterogeneous. Single-cell analysis, on the other hand, offers more
      detailed insight into population variability, thereby facilitating a considerably
      deeper understanding of cell physiology. Although microscopy methods can address
      this issue, they suffer from limitations in terms of the small number of
      individual cells that can be studied and complicated image processing. We
      developed a noninvasive high-throughput method that employs flow cytometry to
      analyze large populations of cells that express pHluorin, a genetically encoded
      ratiometric fluorescent probe that is sensitive to pH. The method described here
      enables measurement of the intracellular pH of single cells with high sensitivity
      and speed, which is a clear improvement compared to previously published methods
      that either require pretreatment of the cells, measure cell populations, or
      require complex data analysis. The ratios of fluorescence intensities, which
      correlate to the intracellular pH, are independent of the expression levels of
      the pH probe, making the use of transiently or extrachromosomally expressed
      probes possible. We conducted an experiment on the kinetics of the pH homeostasis
      of Saccharomyces cerevisiae cultures grown to a stationary phase after ethanol or
      glucose addition and after exposure to weak acid stress and glucose pulse. Minor
      populations with pH homeostasis behaving differently upon treatments were
      identified. 

PMID- 24038690
TI  - Single-cell measurements of enzyme levels as a predictive tool for cellular fates
      during organic acid production.
AB  - Organic acids derived from engineered microbes can replace fossil-derived
      chemicals in many applications. Fungal hosts are preferred for organic acid
      production because they tolerate lignocellulosic hydrolysates and low pH,
      allowing economic production and recovery of the free acid. However, cell death
      caused by cytosolic acidification constrains productivity. Cytosolic
      acidification affects cells asynchronously, suggesting that there is an
      underlying cell-to-cell heterogeneity in acid productivity and/or in resistance
      to toxicity. We used fluorescence microscopy to investigate the relationship
      between enzyme concentration, cytosolic pH, and viability at the single-cell
      level in Saccharomyces cerevisiae engineered to synthesize xylonic acid. We found
      that cultures producing xylonic acid accumulate cells with cytosolic pH below 5
      (referred to here as "acidified"). Using live-cell time courses, we found that
      the probability of acidification was related to the initial levels of xylose
      dehydrogenase and sharply increased from 0.2 to 0.8 with just a 60% increase in
      enzyme abundance (Hill coefficient, >6). This "switch-like" relationship likely
      results from an enzyme level threshold above which the produced acid overwhelms
      the cell's pH buffering capacity. Consistent with this hypothesis, we showed that
      expression of xylose dehydrogenase from a chromosomal locus yields ~20 times
      fewer acidified cells and ~2-fold more xylonic acid relative to expression of the
      enzyme from a plasmid with variable copy number. These results suggest that
      strategies that further reduce cell-to-cell heterogeneity in enzyme levels could
      result in additional gains in xylonic acid productivity. Our results demonstrate
      a generalizable approach that takes advantage of the cell-to-cell variation of a
      clonal population to uncover causal relationships in the toxicity of engineered
      pathways. 

PMID- 24038691
TI  - Termites facilitate methane oxidation and shape the methanotrophic community.
AB  - Termite-derived methane contributes 3 to 4% to the total methane budget globally.
      Termites are not known to harbor methane-oxidizing microorganisms
      (methanotrophs). However, a considerable fraction of the methane produced can be
      consumed by methanotrophs that inhabit the mound material, yet the methanotroph
      ecology in these environments is virtually unknown. The potential for methane
      oxidation was determined using slurry incubations under conditions with high
      (12%) and in situ (~0.004%) methane concentrations through a vertical profile of
      a termite (Macrotermes falciger) mound and a reference soil. Interestingly, the
      mound material showed higher methanotrophic activity. The methanotroph community
      structure was determined by means of a pmoA-based diagnostic microarray. Although
      the methanotrophs in the mound were derived from populations in the reference
      soil, it appears that termite activity selected for a distinct community.
      Applying an indicator species analysis revealed that putative atmospheric methane
      oxidizers (high-indicator-value probes specific for the JR3 cluster) were
      indicative of the active nest area, whereas methanotrophs belonging to both type
      I and type II were indicative of the reference soil. We conclude that termites
      modify their environment, resulting in higher methane oxidation and selecting
      and/or enriching for a distinct methanotroph population. 

PMID- 24038692
TI  - Prevalence of viral photosynthetic and capsid protein genes from cyanophages in
      two large and deep perialpine lakes.
AB  - Cyanophages are important components of aquatic ecosystems, but their genetic
      diversity has been little investigated in freshwaters. A yearlong survey was
      conducted in surface waters of the two largest natural perialpine lakes in France
      (Lake Annecy and Lake Bourget) to investigate part of this cyanophage diversity
      through the analysis of both structural (e.g., g20) and functional (e.g., psbA)
      genes. We found that these cyanophage signature genes were prevalent throughout
      the year but that the community compositions of g20 cyanomyoviruses were
      significantly different between the two lakes. In contrast, psbA-containing
      cyanophages seemed to be more similar between the two ecosystems. We also found
      that a large proportion of g20 sequences grouped with cyanomyophage isolates.
      psbA sequences, belonging to phages of Synechococcus spp., were characterized by
      distinct triplet motifs (with a novel viral triplet motif, EFE). Thus, our
      results show that cyanophages (i) are a diverse viral community in alpine lakes
      and (ii) are clearly distinct from some other freshwater and marine environments,
      suggesting the influence of unique biogeographic factors. 

PMID- 24038693
TI  - Overexpression of fetA (ybbL) and fetB (ybbM), Encoding an Iron Exporter,
      Enhances Resistance to Oxidative Stress in Escherichia coli.
AB  - Reactive oxygen species are generated by redox reactions and the Fenton reaction
      of H2O2 and iron that generates the hydroxyl radical that causes severe DNA,
      protein, and lipid damage. We screened Escherichia coli genomic libraries to
      identify a fragment, containing cueR, ybbJ, qmcA, ybbL, and ybbM, which enhanced
      resistance to H2O2 stress. We report that the DeltaybbL and DeltaybbM strains are
      more susceptible to H2O2 stress than the parent strain and that ybbL and ybbM
      overexpression overcomes H2O2 sensitivity. The ybbL and ybbM genes are predicted
      to code for an ATP-binding cassette metal transporter, and we demonstrate that
      YbbM is a membrane protein. We investigated various metals to identify iron as
      the likely substrate of this transporter. We propose the gene names fetA and fetB
      (for Fe transport) and the gene product names FetA and FetB. FetAB allows for
      increased resistance to oxidative stress in the presence of iron, revealing a
      role in iron homeostasis. We show that iron overload coupled with H2O2 stress is
      abrogated by fetA and fetB overexpression in the parent strain and in the
      Deltafur strain, where iron uptake is deregulated. Furthermore, we utilized whole
      cell electron paramagnetic resonance to show that intracellular iron levels in
      the Deltafur strain are decreased by 37% by fetA and fetB overexpression.
      Combined, these findings show that fetA and fetB encode an iron exporter that has
      a role in enhancing resistance to H2O2-mediated oxidative stress and can minimize
      oxidative stress under conditions of iron overload and suggest that FetAB
      facilitates iron homeostasis to decrease oxidative stress. 

PMID- 24038694
TI  - The Sinorhizobium meliloti ntrX gene is involved in succinoglycan production,
      motility, and symbiotic nodulation on alfalfa.
AB  - Rhizobia establish a symbiotic relationship with their host legumes to induce the
      formation of nitrogen-fixing nodules. This process is regulated by many rhizobium
      regulators, including some two-component regulatory systems (TCSs). NtrY/NtrX, a
      TCS that was first identified in Azorhizobium caulinodans, is required for free
      living nitrogen metabolism and symbiotic nodulation on Sesbania rostrata.
      However, its functions in a typical rhizobium such as Sinorhizobium meliloti
      remain unclear. Here we found that the S. meliloti response regulator NtrX but
      not the histidine kinase NtrY is involved in the regulation of exopolysaccharide
      production, motility, and symbiosis with alfalfa. A plasmid insertion mutant of
      ntrX formed mucous colonies, which overproduced succinoglycan, an
      exopolysaccharide, by upregulating its biosynthesis genes. This mutant also
      exhibited motility defects due to reduced flagella and decreased expression of
      flagellins and regulatory genes. The regulation is independent of the known
      regulatory systems of ExoR/ExoS/ChvI, EmmABC, and ExpR. Alfalfa plants inoculated
      with the ntrX mutant were small and displayed symptoms of nitrogen starvation.
      Interestingly, the deletion mutant of ntrY showed a phenotype similar to that of
      the parent strain. These findings demonstrate that the S. meliloti NtrX is a new
      regulator of succinoglycan production and motility that is not genetically
      coupled with NtrY. 

PMID- 24038695
TI  - Specific midgut region controlling the symbiont population in an insect-microbe
      gut symbiotic association.
AB  - Many insects possess symbiotic bacteria that affect the biology of the host. The
      level of the symbiont population in the host is a pivotal factor that modulates
      the biological outcome of the symbiotic association. Hence, the symbiont
      population should be maintained at a proper level by the host's control
      mechanisms. Several mechanisms for controlling intracellular symbionts of insects
      have been reported, while mechanisms for controlling extracellular gut symbionts
      of insects are poorly understood. The bean bug Riptortus pedestris harbors a
      betaproteobacterial extracellular symbiont of the genus Burkholderia in the
      midgut symbiotic organ designated the M4 region. We found that the M4B region,
      which is directly connected to the M4 region, also harbors Burkholderia symbiont
      cells, but the symbionts therein are mostly dead. A series of experiments
      demonstrated that the M4B region exhibits antimicrobial activity, and the
      antimicrobial activity is specifically potent against the Burkholderia symbiont
      but not the cultured Burkholderia and other bacteria. The antimicrobial activity
      of the M4B region was detected in symbiotic host insects, reaching its highest
      point at the fifth instar, but not in aposymbiotic host insects, which suggests
      the possibility of symbiont-mediated induction of the antimicrobial activity.
      This antimicrobial activity was not associated with upregulation of antimicrobial
      peptides of the host. Based on these results, we propose that the M4B region is a
      specialized gut region of R. pedestris that plays a critical role in controlling
      the population of the Burkholderia gut symbiont. The molecular basis of the
      antimicrobial activity is of great interest and deserves future study. 

PMID- 24038696
TI  - Detection of Achromobacter xylosoxidans in hospital, domestic, and outdoor
      environmental samples and comparison with human clinical isolates.
AB  - Achromobacter xylosoxidans is an aerobic nonfermentative Gram-negative rod
      considered an important emerging pathogen among cystic fibrosis (CF) patients
      worldwide and among immunocompromised patients. This increased prevalence remains
      unexplained, and to date no environmental reservoir has been identified. The aim
      of this study was to identify potential reservoirs of A. xylosoxidans in
      hospital, domestic, and outdoor environments and to compare the isolates with
      clinical ones. From 2011 to 2012, 339 samples were collected in Dijon's
      university hospital, in healthy volunteers' homes in the Dijon area, and in the
      outdoor environment in Burgundy (soil, water, mud, and plants). We designed a
      protocol to detect A. xylosoxidans in environmental samples based on a selective
      medium: MCXVAA (MacConkey agar supplemented with xylose, vancomycin, aztreonam,
      and amphotericin B). Susceptibility testing, genotypic analysis by pulsed-field
      gel electrophoresis, and blaOXA-114 sequencing were performed on the isolates. A
      total of 50 strains of A. xylosoxidans were detected in hospital (33 isolates),
      domestic (9 isolates), and outdoor (8 isolates) samples, mainly in hand washing
      sinks, showers, and water. Most of them were resistant to ciprofloxacin (49
      strains). Genotypic analysis and blaOXA-114 sequencing revealed a wide diversity
      among the isolates, with 35 pulsotypes and 18 variants of oxacillinases.
      Interestingly, 10 isolates from hospital environment were clonally related to
      clinical isolates previously recovered from hospitalized patients, and one
      domestic isolate was identical to one recovered from a CF patient. These results
      indicate that A. xylosoxidans is commonly distributed in various environments and
      therefore that CF patients or immunocompromised patients are surrounded by these
      reservoirs. 

PMID- 24038698
TI  - Identification of CtpL as a chromosomally encoded chemoreceptor for 4
      chloroaniline and catechol in Pseudomonas aeruginosa PAO1.
AB  - Bacterial chemotaxis influences the ability of bacteria to survive and thrive in
      most environments, including polluted ones. Despite numerous reports of the
      phenotypic characterization of chemotactic bacteria, only a few molecular details
      of chemoreceptors for aromatic pollutants have been described. In this study, the
      molecular basis of chemotaxis toward an environmentally toxic chlorinated
      aromatic pollutant, 4-chloroaniline (4CA), was evaluated. Among the three
      Pseudomonas spp. tested, Pseudomonas aeruginosa PAO1 exhibited positive
      chemotaxis both to the nonmetabolizable 4CA, where 4-chloroacetanilide was formed
      as a dead-end transformation product, and to the metabolizable catechol.
      Molecular analysis of all 26 mutants with a disrupted methyl-accepting chemotaxis
      gene revealed that CtpL, a chromosomally encoded chemoreceptor, was responsible
      for the positive chemotactic response toward 4CA. Since CtpL has previously been
      described to be a major chemoreceptor for inorganic phosphate at low
      concentrations in PAO1, this report describes a fortuitous ability of CtpL to
      function toward aromatic pollutants. In addition, its regulation not only was
      dependent on the presence of the chemoattractant inducer but also was regulated
      by conditions of phosphate starvation. These results expand the range of known
      chemotactic transducers and their function in the environmental bacterium PAO1. 

PMID- 24038697
TI  - Development of a tiered multilocus sequence typing scheme for members of the
      Lactobacillus acidophilus complex.
AB  - Members of the Lactobacillus acidophilus complex are associated with functional
      foods and dietary supplements because of purported health benefits they impart to
      the consumer. Many characteristics of these microorganisms are reported to be
      strain specific. Therefore, proper strain typing is essential for safety
      assessment and product labeling, and also for monitoring strain integrity for
      industrial production purposes. Fifty-two strains of the L. acidophilus complex
      (L. acidophilus, L. amylovorus, L. crispatus, L. gallinarum, L. gasseri, and L.
      johnsonii) were genotyped using two established methods and compared to a novel
      multilocus sequence typing (MLST) scheme. PCR restriction fragment length
      polymorphism (PCR-RFLP) analysis of the hsp60 gene with AluI and TaqI
      successfully clustered 51 of the 52 strains into the six species examined, but it
      lacked strain-level discrimination. Random amplified polymorphic DNA PCR (RAPD
      PCR) targeting the M13 sequence resulted in highly discriminatory profiles but
      lacked reproducibility. In this study, an MLST scheme was developed using the
      conserved housekeeping genes fusA, gpmA, gyrA, gyrB, lepA, pyrG, and recA, which
      identified 40 sequence types that successfully clustered all of the strains into
      the six species. Analysis of the observed alleles suggests that nucleotide
      substitutions within five of the seven MLST loci have reached saturation, a
      finding that emphasizes the highly diverse nature of the L. acidophilus complex
      and our unconventional application of a typically intraspecies molecular typing
      tool. Our MLST results indicate that this method could be useful for
      characterization and strain discrimination of a multispecies complex, with the
      potential for taxonomic expansion to a broader collection of Lactobacillus
      species. 

PMID- 24038699
TI  - Regiospecificities and prenylation mode specificities of the fungal indole
      diterpene prenyltransferases AtmD and PaxD.
AB  - We recently reported the function of paxD, which is involved in the paxilline
      (compound 1) biosynthetic gene cluster in Penicillium paxilli. Recombinant PaxD
      catalyzed a stepwise regular-type diprenylation at the 21 and 22 positions of
      compound 1 with dimethylallyl diphosphate (DMAPP) as the prenyl donor. In this
      study, atmD, which is located in the aflatrem (compound 2) biosynthetic gene
      cluster in Aspergillus flavus and encodes an enzyme with 32% amino acid identity
      to PaxD, was characterized using recombinant enzyme. When compound 1 and DMAPP
      were used as substrates, two major products and a trace of minor product were
      formed. The structures of the two major products were determined to be reversely
      monoprenylated compound 1 at either the 20 or 21 position. Because compound 2 and
      beta-aflatrem (compound 3), both of which are compound 1-related compounds
      produced by A. flavus, have the same prenyl moiety at the 20 and 21 position,
      respectively, AtmD should catalyze the prenylation in compound 2 and 3
      biosynthesis. More importantly and surprisingly, AtmD accepted paspaline
      (compound 4), which is an intermediate of compound 1 biosynthesis that has a
      structure similar to that of compound 1, and catalyzed a regular monoprenylation
      of compound 4 at either the 21 or 22 position, though the reverse prenylation was
      observed with compound 1. This suggests that fungal indole diterpene
      prenyltransferases have the potential to alter their position and regular/reverse
      specificities for prenylation and could be applicable for the synthesis of
      industrially useful compounds. 

PMID- 24038700
TI  - Species co-occurrence patterns among Lyme borreliosis pathogens in the tick
      vector Ixodes ricinus.
AB  - Mixed infections have important consequences for the ecology and evolution of
      host-parasite interactions. In vector-borne diseases, interactions between
      pathogens occur in both the vertebrate host and the arthropod vector. Spirochete
      bacteria belonging to the Borrelia burgdorferi sensu lato genospecies complex are
      transmitted by Ixodes ticks and cause Lyme borreliosis in humans. In Europe,
      there is a high diversity of Borrelia pathogens, and the main tick vector, Ixodes
      ricinus, is often infected with multiple Borrelia genospecies. In the present
      study, we characterized the pairwise interactions between five B. burgdorferi
      sensu lato genospecies in a large data set of I. ricinus ticks collected from the
      same field site in Switzerland. We measured two types of pairwise interactions:
      (i) co-occurrence, whether double infections occurred more or less often than
      expected, and (ii) spirochete load additivity, whether the total spirochete load
      in double infections was greater or less than the sum of the single infections.
      Mixed infections of Borrelia genospecies specialized on different vertebrate
      reservoir hosts occurred less frequently than expected (negative co-occurrence)
      and had joint spirochete loads that were lower than the additive expectation
      (inhibition). In contrast, mixed infections of genospecies that share the same
      reservoir hosts were more common than expected (positive co-occurrence) and had
      joint spirochete loads that were similar to or greater than the additive
      expectation (facilitation). Our study suggests that the vertebrate host plays an
      important role in structuring the community of B. burgdorferi sensu lato
      genospecies inside the tick vector. 

PMID- 24038701
TI  - Acquired genetic mechanisms of a multiresistant bacterium isolated from a
      treatment plant receiving wastewater from antibiotic production.
AB  - The external environment, particularly wastewater treatment plants (WWTPs), where
      environmental bacteria meet human commensals and pathogens in large numbers, has
      been highlighted as a potential breeding ground for antibiotic resistance. We
      have isolated the extensively drug-resistant Ochrobactrum intermedium CCUG 57381
      from an Indian WWTP receiving industrial wastewater from pharmaceutical
      production contaminated with high levels of quinolones. Antibiotic susceptibility
      testing against 47 antibiotics showed that the strain was 4 to >500 times more
      resistant to sulfonamides, quinolones, tetracyclines, macrolides, and the
      aminoglycoside streptomycin than the type strain O. intermedium LMG 3301T. Whole
      genome sequencing identified mutations in the Indian strain causing amino acid
      substitutions in the target enzymes of quinolones. We also characterized three
      acquired regions containing resistance genes to sulfonamides (sul1),
      tetracyclines [tet(G) and tetR], and chloramphenicol/florfenicol (floR).
      Furthermore, the Indian strain harbored acquired mechanisms for horizontal gene
      transfer, including a type I mating pair-forming system (MPFI), a MOBP relaxase,
      and insertion sequence transposons. Our results highlight that WWTPs serving
      antibiotic manufacturing may provide nearly ideal conditions for the recruitment
      of resistance genes into human commensal and pathogenic bacteria.

PMID- 24038702
TI  - Changing dietary calcium-phosphorus level and cereal source selectively alters
      abundance of bacteria and metabolites in the upper gastrointestinal tracts of
      weaned pigs.
AB  - Several dietary ingredients may affect the bacterial community structure and
      metabolism in the porcine gut and may therefore influence animals' health and
      performance. This study investigated the effects of cereal source and calcium
      phosphorus (CaP) level in the diet on bacterial microbiota and metabolites,
      nutrient intake, and gut environment in weaned pigs. Pigs (n=8/treatment) were
      fed wheat-barley- or corn-based diets with an adequate or high CaP level for 14
      days. Effects on microbiota in the stomach, ileum, and midcolon were assessed
      using quantitative PCR. Data showed that Enterobacteriaceae, Campylobacter spp.,
      and Helicobacter spp., which all contain highly immune reactive
      lipopolysaccharide (LPS), were abundant at all gut sites. Diet effects on
      bacteria and metabolites were moderate and occurred mainly in the upper gut,
      whereas no effects on bacteria, fermentation products, and LPS could be observed
      in the colon. Differences in carbohydrate intake with corn versus wheat-barley
      diets selectively stimulated Bifidobacterium in the stomach and ileum. There was
      a growth advantage for a few bacterial groups in the stomach and ileum of pigs
      fed the high versus adequate CaP level (i.e., gastric Enterobacteriaceae and
      ileal Enterococcus, Bacteroides-Prevotella-Porphyromonas, and Campylobacter).
      Interestingly, gastrointestinal pH was not affected by dietary CaP level. The
      present findings demonstrate the stability of the bacterial community and gut
      environment toward dietary changes even in young pigs. The results on stimulation
      of gastric and ileal Bifidobacterium by corn diets may be employed in nutritional
      strategies to support gut health after weaning.

PMID- 24038704
TI  - Aspergillus fumigatus SidJ mediates intracellular siderophore hydrolysis.
AB  - Siderophore-mediated iron handling is crucial for the virulence of Aspergillus
      fumigatus. Here we identified a new component of its siderophore metabolism,
      termed SidJ, which is encoded by AFUA_3G03390. The encoding gene is localized in
      a siderophore biosynthetic gene cluster that is conserved in a variety of fungi.
      During iron starvation, SidJ deficiency resulted in decreased growth and
      increased intracellular accumulation of hydrolysis products of the siderophore
      fusarinine C. The implied role in siderophore hydrolysis is consistent with a
      putative esterase domain in SidJ, which now represents the first functionally
      characterized member of the DUF1749 (domain of unknown function) protein family,
      with members found exclusively in fungi and plants. 

PMID- 24038703
TI  - CelR, an ortholog of the diguanylate cyclase PleD of Caulobacter, regulates
      cellulose synthesis in Agrobacterium tumefaciens.
AB  - Cellulose fibrils play a role in attachment of Agrobacterium tumefaciens to its
      plant host. While the genes for cellulose biosynthesis in the bacterium have been
      identified, little is known concerning the regulation of the process. The signal
      molecule cyclic di-GMP (c-di-GMP) has been linked to the regulation of
      exopolysaccharide biosynthesis in many bacterial species, including A.
      tumefaciens. In this study, we identified two putative diguanylate cyclase genes,
      celR (atu1297) and atu1060, that influence production of cellulose in A.
      tumefaciens. Overexpression of either gene resulted in increased cellulose
      production, while deletion of celR, but not atu1060, resulted in decreased
      cellulose biosynthesis. celR overexpression also affected other phenotypes,
      including biofilm formation, formation of a polar adhesion structure, plant
      surface attachment, and virulence, suggesting that the gene plays a role in
      regulating these processes. Analysis of celR and Deltacel mutants allowed
      differentiation between phenotypes associated with cellulose production, such as
      biofilm formation, and phenotypes probably resulting from c-di-GMP signaling,
      which include polar adhesion, attachment to plant tissue, and virulence.
      Phylogenetic comparisons suggest that species containing both celR and celA,
      which encodes the catalytic subunit of cellulose synthase, adapted the CelR
      protein to regulate cellulose production while those that lack celA use CelR,
      called PleD, to regulate specific processes associated with polar localization
      and cell division. 

PMID- 24038705
TI  - Accumulation and inactivation of avian influenza virus by the filter-feeding
      invertebrate Daphnia magna.
AB  - The principal mode of avian influenza A virus (AIV) transmission among wild birds
      is thought to occur via an indirect fecal-oral route, whereby individuals are
      exposed to virus from the environment through contact with virus-contaminated
      water. AIV can remain viable for an extended time in water; however, little is
      known regarding the influence of the biotic community (i.e., aquatic
      invertebrates) on virus persistence and infectivity in aquatic environments. We
      conducted laboratory experiments to investigate the ability of an aquatic filter
      feeding invertebrate, Daphnia magna, to accumulate virus from AIV-dosed water
      under the hypothesis that they represent a potential vector of AIV to waterfowl
      hosts. We placed live daphnids in test tubes dosed with low-pathogenicity AIV
      (H3N8 subtype isolated from a wild duck) and sampled Daphnia tissue and the
      surrounding water using reverse transcription-quantitative PCR (RT-qPCR) at 3- to
      120-min intervals for up to 960 min following dosing. Concentrations of viral RNA
      averaged 3 times higher in Daphnia tissue than the surrounding water shortly
      after viral exposure, but concentrations decreased exponentially through time for
      both. Extracts from Daphnia tissue were negative for AIV by cell culture, whereas
      AIV remained viable in water without Daphnia present. Our results suggest
      daphnids can accumulate AIV RNA and effectively remove virus particles from
      water. Although concentrations of viral RNA were consistently higher in Daphnia
      tissue than the water, additional research is needed on the time scale of AIV
      inactivation after Daphnia ingestion to fully elucidate Daphnia's role as a
      potential vector of AIV infection to aquatic birds. 

PMID- 24038706
TI  - Cognitive emotion regulation strategies as predictors of depressive symptoms in
      women newly diagnosed with breast cancer.
AB  - OBJECTIVE: This study aimed to determine the effects of cognitive emotion
      regulation strategies on depressive symptoms in women with breast cancer.
      METHODS: Five hundred and nine women with breast cancer completed a demographic
      survey, the Chinese version of Cognitive Emotion Regulation Questionnaire (CERQ
      C), and the Center for Epidemiological Studies Depression Scale (CES-D) at the
      initial assessment (T1). One month later (T2), 504 patients completed the CES-D.
      Patients were assigned to four groups: H-H (CES-D scores >=16 at both
      timepoints), H-L (CES-D score >=16 at T1, <16 at T2), L-H (CES-D score <16 at T1,
      >=16 at T2) and L-L (CES-D scores <16 at both timepoints). RESULTS: Over 80%
      patients had mild or no depressive symptoms at both timepoints. There were
      significant group differences in cognitive emotion regulation strategies. CERQ-C
      subscale scores for adaptive strategies were higher, and scores for maladaptive
      strategies were lower among patients in L-L and H-L groups than among those in H
      H group. Hierarchical regression analyses showed that cognitive emotion
      regulation strategies at T1 differentiated depressive symptoms at T2, accounting
      for 56.5% of variance after controlling for sociodemographic and biological
      variables and baseline levels of depression. Greater acceptance, positive
      refocusing, and positive reappraisal at T1 were associated with fewer depressive
      symptoms at T2. CONCLUSIONS: Cognitive emotion regulation strategies accounted
      for considerable variance in depressive symptom scores 1 month later. The
      strategies of acceptance, positive refocusing, and positive reappraisal may be
      beneficial for women with breast cancer. Intervention studies are needed to
      confirm if these associations are causal.

PMID- 24038707
TI  - Controlling the molecular topology of vinylogous iminium ions by logical
      substrate design: highly regio- and stereoselective aminocatalytic 1,6-addition
      to linear 2,4-dienals.

PMID- 24038708
TI  - Positive and negative caregiver experiences in first-episode psychosis: emotional
      overinvolvement, wellbeing and metacognition.
AB  - OBJECTIVES: While caregivers of persons with first-episode psychosis often report
      a range of negative experiences, little is known about what psychological factors
      are involved. The aim of this study was to examine how caregivers' general
      wellbeing, emotional overinvolvement and metacognition influenced their reports
      of both positive and negative caregiving experiences. DESIGN: A prospective
      consecutive cross-sectional study. METHODS: Forty caregivers of patients with
      first-episode psychosis were interviewed using semi-structured interview and
      questionnaires. RESULTS: Greater levels of distress and overinvolvement were
      associated with more negative experiences of caregiving while greater
      metacognitive capacity was associated with more positive experiences of
      caregiving. CONCLUSIONS: The experience of positive and negative aspects of
      caregiving seems to be associated with different variables. Greater metacognitive
      capacity does not necessarily alleviate the suffering and distress, which is a
      healthy and normal reaction to having a close one suffering from psychosis. But
      it might help broaden the perspective, allowing for both negative and positive
      experiences. Clinical implications in terms of expanding the range of therapeutic
      interventions are discussed. PRACTITIONER POINTS: Assessing the capacity for
      metacognition in a non-clinical population. Understanding what factors are
      involved in positive and negative caregiver experiences in first-episode
      psychosis. A broadening of family interventions by encompassing the concept of
      metacognition.

PMID- 24038709
TI  - Amyloid fibril formation in vitro from halophilic metal binding protein: its high
      solubility and reversibility minimized formation of amorphous protein
      aggregations.
AB  - Halophilic proteins are characterized by high net negative charges and relatively
      small fraction of hydrophobic amino acids, rendering them aggregation resistant.
      These properties are also shared by histidine-rich metal binding protein (HP)
      from moderate halophile, Chromohalobacter salexigens, used in this study. Here,
      we examined how halophilic proteins form amyloid fibrils in vitro. His-tagged HP,
      incubated at pH 2.0 and 58 degrees C, readily formed amyloid fibrils, as observed
      by thioflavin fluorescence, CD spectra, and transmission or atomic force
      microscopies. Under these low-pH harsh conditions, however, His-HP was promptly
      hydrolyzed to smaller peptides most likely responsible for rapid formation of
      amyloid fibril. Three major acid-hydrolyzed peptides were isolated from fibrils
      and turned out to readily form fibrils. The synthetic peptides predicted to form
      fibrils in these peptide sequences by Waltz software also formed fibrils. Amyloid
      fibril was also readily formed from full-length His-HP when incubated with 10-20%
      2,2,2-trifluoroethanol at pH 7.8 and 25 degrees C without peptide bond cleavage. 

PMID- 24038710
TI  - Catheterization laboratory activation during mechanical cardiopulmonary
      resuscitation: when should we say "No?".
AB  - Sudden cardiac arrest is a devastating manifestation of coronary artery disease
      and a leading cause of death in the western world. Early and effective
      cardiopulmonary resuscitation is essential for return of spontaneous circulation.
      If manual compression is ongoing and return of spontaneous circulation has not
      been achieved, the prognosis is poor, and the logistics of performing cardiac
      catheterization are forbidding. With the advent of mechanical chest compression,
      however, this clinical scenario has become much more complex. Coronary
      angiography and percutaneous coronary intervention, although still cumbersome,
      has been established as feasible with ongoing mechanical chest compression. This
      article discusses the strengths and pitfalls of mechanical cardiopulmonary
      resuscitation, our experience, and current evidence behind activation of the
      catheterization laboratory with ongoing mechanical chest compression.

PMID- 24038711
TI  - Amine-free approach toward N-toluenesulfonyl amidine construction: a phosphite
      mediated Beckmann-like coupling of oximes and p-toluenesulfonyl azide.
AB  - Atom hopping: A chlorophosphite-mediated Beckmann ligation of oximes and p
      toluenesulfonyl azide gives access to N-sulfonyl phosphoramidines in good to
      excellent yields. The reaction proceeds under exceptionally mild conditions and
      constitutes a bioorthogonal approach toward amidines by avoiding the use of
      amines and transition-metal catalysts. dmp-ol=3,3-dimethylpropanediol. 

PMID- 24038712
TI  - Chemical inhomogeneity, short-range order, and magnetism in the LiNiO2 -NiO solid
      solution.
AB  - NiO:Li is an early exemplar for which hole-doping of a correlated insulator gives
      rise to rich and varied magnetic behavior. It is also an important system from
      the viewpoint of p-type transparent conducting oxides, and is representative of a
      large class of materials that have been used in lithium ion batteries, since the
      end-member compound, LiNiO2 , belongs to the class of layered cathode materials.
      Despite the deceptive structural and compositional simplicity of this system, a
      complete understanding of its complex magnetic properties has remained elusive.
      Here a comprehensive investigation of the solid solution Lix Ni2-x O2 , examining
      samples of precise stoichiometry using a combination of high-resolution
      synchrotron X-ray powder diffraction and SQUID magnetometry, is provided. The
      focus is on the interesting region between 0.40<x<1.00 in which the magnetic
      ordering temperature changes drastically with composition. The magnetism evolves
      from strong G-type antiferromagnetism of x=0.40 with TN =327 K to robust
      uncompensated magnetic order at TN =240 K when x is close to 0.7, and to glassy A
      type antiferromagnetism of x=1.00 at TN =9 K. This study demonstrates this
      magnetic behavior is linked to the Li-Ni chemical order that develops from short-
      to long-range. The interfaces between ordered domains give rise to magnetic
      exchange bias, which manifests as a shift in the magnetization-field loop for
      samples with nanoscale coherence lengths (0.54<x<0.66). 

PMID- 24038713
TI  - Altered resting-state network connectivity in congenital blind.
AB  - The brain of congenital blind (CB) has experienced a series of structural and
      functional alterations, either undesirable outcomes such as atrophy of the visual
      pathway due to sight loss from birth, or compensatory plasticity to interact
      efficiently with the environment. However, little is known, so far, about
      alterations in the functional architecture of resting-state networks (RSNs) in
      CB. This study aimed to investigate intra- and internetwork connectivity
      differences between CB and sighted controls (SC), using independent component
      analysis (ICA) on resting state functional MRI data. Compared with SC, CB showed
      significantly increased network connectivity within the salience network (SN) and
      the occipital cortex. Moreover, CB exhibited enhanced internetwork connectivity
      between the SN and the frontoparietal network (FPN) and between the FPN and the
      occipital cortex; however, they showed decreased internetwork connectivity
      between the occipital cortex and the sensorimotor network. These findings suggest
      that CB experience large scale reorganization at the level of the functional
      network. More importantly, the enhanced intra- and internetwork connectivity of
      the SN, FPN, and occipital cortex in CB may improve their abilities to identify
      salient stimuli, to initiate the executive function, and to top-down control of
      attention, which are critical for the CB to guide appropriate behavior and to
      better adaption to the environment.

PMID- 24038714
TI  - Commentary: Back to the future with Sir Bradford Hill: statistical analysis with
      hospital-acquired infections.

PMID- 24038715
TI  - A critical evaluation of statistical approaches to examining the role of growth
      trajectories in the developmental origins of health and disease.
AB  - The developmental origins of health and disease hypothesis suggests that small
      birth size in conjunction with rapid compensatory childhood growth might yield a
      greater risk of developing chronic diseases in later life. For example, there is
      evidence that people who developed coronary heart disease and diabetes
      experienced different growth trajectories from those who did not develop these
      diseases. However, some of the methods used in these articles may have been
      flawed. We critically evaluate proposed approaches for identifying the growth
      trajectories distinctive to those developing later disease and identifying
      critical phases of growth during the early lifecourse. Among the approaches we
      examined (tracing the z-scores, lifecourse plots and models, lifecourse path
      analysis, conditional body size analysis, multilevel analysis, latent growth
      curve models and growth mixture models) conditional body size analysis,
      multilevel analysis, latent growth curve models and growth mixture models are
      least prone to collinearity problems caused by repeated measures. Multilevel
      analysis is more flexible when body size is not measured at the same age for all
      cohort members. Strengths and weaknesses of each approach are illustrated using
      real data. Demonstrating the influence of growth trajectories on later disease is
      complex and challenging; therefore, it is likely that a combination of approaches
      will be required to unravel the complexity in lifecourse research. 

PMID- 24038716
TI  - Culpability analysis is still a valuable technique.

PMID- 24038717
TI  - Hospital-acquired infections--appropriate statistical treatment is urgently
      needed!
AB  - Research on hospital-acquired infections (HAIs) requires the highest
      methodological standards to minimize the risk of bias and to avoid misleading
      interpretation. There are two major issues related specifically to studies in
      this area, namely the timing of infection and the occurrence of so-called
      competing risks, which deserve special attention. Just as a patient who acquires
      a serious infection during hospital admission needs appropriate antibiotic
      treatment, data being collected in studies on hospital-acquired infections need
      appropriate statistical analysis. We illustrate the urgent need for appropriate
      statistical treatment of hospital-acquired infections with some examples from
      recently conducted studies.The considerations presented are relevant for
      investigations on risk factors for HAIs as well as for outcome studies. 

PMID- 24038718
TI  - Virus-mimetic cytoplasm-cleavable magnetic/silica nanoclusters for enhanced gene
      delivery to mesenchymal stem cells.
AB  - It does get in: Phage is made of DNA as a core and protein as a coat, and it can
      transfer DNA into host cells with high efficiency. Phage-mimetic gene transfer to
      hard-to-transfect mesenchymal stem cells (MSCs) was achieved using virus-mimetic
      magnetic silica nanoclusters (VMSNCs). The VMSNCs bear MSC-homing phage-borne
      protein on the surface and encapsulate DNA inside, promoting the transfer of DNA
      into MSCs. 

PMID- 24038721
TI  - Pd-Cu(2)O and Ag-Cu(2)O hybrid concave nanomaterials for an effective synergistic
      catalyst.
AB  - Palladium and silver salts were combined with Cu2 O octadecahedra in concave
      heterostructures. The formation of concave faces involved selective oxidative
      etching of Cu2 O on the {100} faces and in situ growth of Pd/Ag on different
      sites. The structures showed superior catalytic activities to both single domains
      and their mixtures in a model Sonogashira-type organic reaction. 

PMID- 24038719
TI  - Signal detection on spontaneous reports of adverse events following immunisation:
      a comparison of the performance of a disproportionality-based algorithm and a
      time-to-onset-based algorithm.
AB  - PURPOSE: Disproportionality methods measure how unexpected the observed number of
      adverse events is. Time-to-onset (TTO) methods measure how unexpected the TTO
      distribution of a vaccine-event pair is compared with what is expected from other
      vaccines and events. Our purpose is to compare the performance associated with
      each method. METHODS: For the disproportionality algorithms, we defined 336
      combinations of stratification factors (sex, age, region and year) and threshold
      values of the multi-item gamma Poisson shrinker (MGPS). For the TTO algorithms,
      we defined 18 combinations of significance level and time windows. We used
      spontaneous reports of adverse events recorded for eight vaccines. The vaccine
      product labels were used as proxies for true safety signals. Algorithms were
      ranked according to their positive predictive value (PPV) for each vaccine
      separately; amedian rank was attributed to each algorithm across vaccines.
      RESULTS: The algorithm with the highest median rank was based on TTO with a
      significance level of 0.01 and a time window of 60 days after immunisation. It
      had an overall PPV 2.5 times higher than for the highest-ranked MGPS algorithm,
      16(th) rank overall, which was fully stratified and had a threshold value of 0.8.
      A TTO algorithm with roughly the same sensitivity as the highest-ranked MGPS had
      better specificity but longer time-to-detection. CONCLUSIONS: Within the scope of
      this study, the majority of the TTO algorithms presented a higher PPV than for
      any MGPS algorithm. Considering the complementarity of TTO and disproportionality
      methods, a signal detection strategy combining them merits further investigation.
      (c) 2013 GlaxoSmithKline. Pharmacoepidemiology and Drug Safety published by John
      Wiley & Sons, Ltd.

PMID- 24038722
TI  - Intestinal-type adenocarcinoma of the larynx: Report of a rare aggressive
      phenotype and discussion of histogenesis.
AB  - BACKGROUND: Primary laryngeal adenocarcinomas are uncommon and typically of
      salivary or seromucinous glands origin. Similarly, metastatic adenocarcinoma,
      including intestinal origin to the larynx, is a rare occurrence. METHODS: We
      present a case of a 63-year-old woman with odynophagia and an epiglottic mass of
      2 months' duration. Physical examination revealed a large mass involving the
      entire epiglottis with extension to the preepiglottic space anteriorly and to the
      right lateral wall of the oropharyngeal/hypopharyngeal junction. RESULTS:
      Induction chemotherapy was initiated, and, after 4 cycles with no noticeable
      response, the patient underwent total laryngectomy and bilateral levels II to IV
      neck dissection. The final pathology diagnosis was primary intestinal-type
      adenocarcinoma of the larynx. CONCLUSION: We present a primary high-stage
      intestinal-type adenocarcinoma of the larynx and discuss its putative origin and
      the clinicopathologic characteristics.

PMID- 24038723
TI  - Absolute lymphocyte counts as prognostic indicators for immune thrombocytopenia
      outcomes in children.
AB  - BACKGROUND: Recent studies reviewing immune mechanisms of immune thrombocytopenia
      (ITP) have suggested acute and chronic forms may represent distinct
      immunopathological disorders. This study evaluated absolute lymphocyte counts
      (ALCs) as predictors for ITP outcomes. PROCEDURE: CBCs with differential counts
      were ascertained at presentation, 3, 6, and 12 months for 204 patients. Receiver
      operating characteristic (ROC) curves were used to determine cutoff values.
      Logistic regression models and recursive partitioning were used to evaluate which
      variables were significantly associated with outcomes. RESULTS: ALC values at
      presentation were not independently predictive of disease duration. However, ALC
      values at 3 months were significant predictors. Sixty-eight percent (40/59) of
      patients >8 years of age and 43% (20/46) of patients <= 8 years who had an ALC <=
      3,000/MUl at 3 months developed chronic ITP. This compares to chronic rates of
      only 25% (3/12) and 2% (2/87) of patients >8 and <= 8 years, respectively, with
      an ALC > 3,000/MUl at 3 months. Further, 92% (60/65) of patients who developed
      chronic ITP had a 3-month ALC <= 3,000/MUl. An ALC > 3,000/MUl at 3 months is a
      strong predictor for platelet recovery as only 5% (5/99) of these patients
      developed chronic ITP. CONCLUSION: This study suggests progression to lower
      lymphocyte counts over the first few months of disease is a strong predictor for
      chronic ITP, allowing for risk stratification of patients, particularly when used
      in conjunction with other known predictors. Further research is needed to confirm
      these findings and to fully investigate the pathophysiological mechanisms
      responsible for this association.

PMID- 24038724
TI  - Systematic investigation of elevated cholestatic enzymes during the third
      posttransplant month.

PMID- 24038725
TI  - Brief report: Rx1 defines retinal precursor identity by repressing alternative
      fates through the activation of TLE2 and Hes4.
AB  - The molecular mechanisms underlying the acquisition of retinal precursor identity
      are scarcely defined. Although the homeobox gene Rx1 (also known as Rax) plays a
      major role in specifying retinal precursors and maintaining their multipotent
      state, the involved mechanisms remain to be largely deciphered. Here, following a
      highthroughput screen for genes regulated by Rx1, we found that this
      transcription factor specifies the fate of retinal progenitors by repressing
      genes normally activated in adjacent ectodermal territories. Unexpectedly, we
      also observed that Rx1, mainly through the activation of the transcriptional
      repressors TLE2 and Hes4, is necessary and sufficient to inhibit endomesodermal
      gene expression in retinal precursors of the eye field. In particular, Rx1
      knockdown leads retinogenic blastomeres to adopt an endomesodermal fate,
      indicating a previously undescribed function for Rx1 in preventing the expression
      of endomesoderm determinants known to inhibit retinal fate. Altogether these data
      suggest that an essential requirement to establish a retinal precursor identity
      is the active inhibition of pathways leading to alternative fates.

PMID- 24038726
TI  - Delaunay-based nonlocal interactions are sufficient and accurate in protein fold
      recognition.
AB  - This study is aimed at showing that considering only nonlocal interactions
      (interactions of two atoms with a sequence separation larger than five amino
      acids) extracted using Delaunay tessellation is sufficient and accurate for
      protein fold recognition. An atomic knowledge-based potential was extracted based
      on a Delaunay tessellation with 167 atom types from a sample of the native
      structures and the normalized energy was calculated for only nonlocal
      interactions in each structure. The performance of this method was tested on
      several decoy sets and compared to a method considering all interactions
      extracted by Delaunay tessellation and three other popular scoring functions.
      Features such as the contents of different types of interactions and atoms with
      the highest number of interactions were also studied. The results suggest that
      considering only nonlocal interactions in a Delaunay tessellation of protein
      structure is a discrete structure catching deep properties of the three
      dimensional protein data.

PMID- 24038727
TI  - Procarbazine and antidepressants: a retrospective review of the risk of serotonin
      toxicity.
AB  - BACKGROUND: Procarbazine is an anticancer agent that also inhibits monoamine
      oxidase, an enzyme responsible for the metabolism of various catecholamines,
      including serotonin. METHODS: A retrospective chart review of lymphoma patients
      who were treated with both procarbazine and an antidepressant, as well as
      procarbazine alone, was performed to determine if signs and symptoms of serotonin
      toxicity were present. RESULTS: A total of 65 patients received procarbazine
      between 2004 and 2010 and were eligible to be included in the study. Twenty-six
      of these patients received an antidepressant in combination with procarbazine,
      with selective serotonin reuptake inhibitors being the most common type of
      antidepressant. No patients in the study were diagnosed with serotonin toxicity,
      nor did any meet Hunter's diagnostic criteria for serotonin toxicity. Diarrhea,
      tremor, and shivering were the symptoms from Sternbach's criteria that were
      further analyzed, with diarrhea occurring 8.54% of the time, tremor occurring
      5.53% of the time, and shivering occurring 2.51% of the time in patients who
      received an antidepressant with their procarbazine. Despite these symptoms, the
      diagnosis of serotonin toxicity according to Sternbach's criteria was determined
      to be unlikely. CONCLUSIONS: In this small sample of patients treated with
      procarbazine plus an antidepressant (most typically SSRIs), there were no reports
      of serotonin toxicity, nor did any patients demonstrate symptoms consistent with
      serotonin toxicity. The authors urge clinicians to ensure depression is
      adequately managed in cancer patients who are undergoing procarbazine therapy,
      starting with typical first-line antidepressant agents.

PMID- 24038729
TI  - Opsin, a structural model for olfactory receptors?
AB  - Receptor-ligand interaction: Olfactory receptors (ORs) are G-protein-coupled
      receptors (GPCRs), which detect signaling molecules such as hormones and
      odorants. The structure of opsin, the GPCR employed in vision, with a detergent
      molecule bound deep in its orthosteric ligand-binding pocket provides a template
      for OR homology modeling, thus enabling investigation of the structural basis of
      the mechanism of odorant-receptor recognition. 

PMID- 24038728
TI  - Sleep quality predicts treatment outcome in CBT for social anxiety disorder.
AB  - BACKGROUND: Sleep quality may be an important, yet relatively neglected,
      predictor of treatment outcome in cognitive-behavioral therapy (CBT) for anxiety
      disorders. Specifically, poor sleep quality may impair memory consolidation of in
      session extinction learning. We therefore examined sleep quality as a predictor
      of treatment outcome in CBT for social anxiety disorder and the impact of d
      cycloserine (DCS) on this relationship. METHODS: One hundred sixty-nine
      participants with a primary diagnosis of DSM-IV generalized social anxiety
      disorder were recruited across three sites. Participants were enrolled in 12
      weeks of group CBT. Participants randomly received 50 mg of DCS (n = 87) or pill
      placebo (n = 82) 1 hr prior to sessions 3-7. Participants completed a baseline
      measure of self-reported sleep quality and daily diaries recording subjective
      feelings of being rested upon wakening. Outcome measures including social anxiety
      symptoms and global severity scores were assessed at each session. RESULTS:
      Poorer baseline sleep quality was associated with slower improvement and higher
      posttreatment social anxiety symptom and severity scores. Moreover, patients who
      felt more "rested" after sleeping the night following a treatment session had
      lower levels of symptoms and global severity at the next session, controlling for
      their symptoms and severity scores the previous session. Neither of these effects
      were moderated by DCS condition. CONCLUSIONS: Our findings suggest that poor
      sleep quality diminishes the effects of CBT for social anxiety disorder and this
      relation is not attenuated by DCS administration. Therapeutic attention to sleep
      quality prior to initiation of CBT and during the acute treatment phase may be
      clinically indicated.

PMID- 24038730
TI  - Superoxide reductase: different interaction modes with its two redox partners.
AB  - Anaerobic organisms have molecular systems to detoxify reactive oxygen species
      when transiently exposed to oxygen. One of these systems is superoxide reductase,
      which reduces O2 (.-) to H2 O2 without production of molecular oxygen. In order
      to complete the reduction of superoxide anion, superoxide reductase requires an
      electron, delivered by its redox partners, which in Desulfovibrio gigas are
      rubredoxin and/or desulforedoxin. In this work, we characterized the interaction
      of Desulfovibrio gigas superoxide reductase with both electron donors by using
      steady-state kinetics, 2D NMR titrations, and backbone relaxation measurements.
      The rubredoxin surface involved in the electron transfer complex with superoxide
      reductase comprises the solvent-exposed hydrophobic residues in the vicinity of
      its metal center (Cys9, Gly10, Cys42, Gly43, and Ala44), and a Kd of 3 MUM at 59
      mM ionic strength was estimated by NMR. The ionic strength dependence of
      superoxide-mediated rubredoxin oxidation by superoxide reductase has a maximum
      kapp of (37 +/- 12) min(-1) at 157 mM. Relative to the electron donor
      desulforedoxin, its complex with superoxide reductase was not detected by
      chemical shift perturbation, though this protein is able to transfer electrons to
      superoxide reductase with a maximum kapp of (31 +/- 7) min(-1) at an ionic
      strength of 57 mM. Competition experiments using steady-state kinetics and NMR
      spectroscopy (backbone relaxation measurements and use of a paramagnetic
      relaxation enhancement probe) with Fe-desulforedoxin in the presence of (15) N-Zn
      rubredoxin showed that these two electron donors compete for the same site on the
      enzyme surface, as shown in the model structure of the complex generated by using
      restrained molecular docking calculations. These combined strategies indicate
      that the two small electron donors bind in different manners, with the
      desulforedoxin complex being a short lived electron transfer complex or more
      dynamic, with many equivalent kinetically competent orientations.

PMID- 24038731
TI  - "Zero-dimensional" single-walled carbon nanotubes.
AB  - The shorter, the more dispersible: An iterative, emulsion-based shortening
      technique has been used to reduce the length of single-walled carbon nanotubes
      (SWNTs) to the same order of magnitude as their diameter (ca. 1 nm), thus
      achieving an effectively "zero-dimensional" structure with improved
      dispersibility and, after hydroxylation, long-term water solubility. Finally,
      zero-dimensional SWNTs were positively identified using mass spectrometry for the
      first time. 

PMID- 24038732
TI  - Rapid high-specificity microRNA detection using a two-stage isotachophoresis
      assay.
AB  - Focusing in on the small: A two-stage microRNA detection assay uses
      electrokinetic focusing to speed up hybridization and a functionalized hydrogel
      for affinity purification. This method detects microRNAs in 15 minutes with
      single-nucleotide specificity, and processes only 5 ng of total RNA. 

PMID- 24038733
TI  - Folding of 16S rRNA in a signal-producing structure for the detection of
      bacteria.
AB  - Sixty-four DNA strands hybridize to 16S rRNA to form 32 deoxyribozyme catalytic
      cores that produce a fluorescent signal. The approach allows detection of 0.6 pM
      16S rRNA, or about 3*10(4) bacterial cells in a PCR-free format.

PMID- 24038735
TI  - Long-term retinoblastoma follow-up with or without general anaesthesia.
AB  - BACKGROUND: Children with treated retinoblastoma undergo frequent examinations to
      monitor for recurrent or new tumours. Examinations under anaesthesia allow a more
      complete examination in younger children, however they are stressful for the
      family, subject the child to medical risk and consume resources. The risk of
      recurrent or new tumours declines with age and it is common practice to examine
      older children without general anaesthesia. There are no studies on the safety
      and cost effectiveness of this practice, or guidelines on when examination
      without anaesthesia (EWA) can be safely commenced. PROCEDURE: Retrospective case
      note review of 128 sequential patients treated for retinoblastoma in a national
      referral centre over 10 years. RESULTS: Following exclusions, 113 eyes of 84
      children were analysed. The mean age at diagnosis was 20 months (range birth to
      71 months). There were 55 unilateral and 29 bilateral cases. The mean follow-up
      was 77.7 months (range 12-178 months). EWA was commenced at a mean age of 53
      months (range 12-98 months). The age of conversion to EWA was largely dependent
      on child cooperation and disease activity. Tumour activity was detected on EWA in
      one child at the age of 86 months, 9 months after the last active treatment and
      treated successfully. CONCLUSIONS: Examination without general anaesthesia does
      not appear to expose children to an increased risk of undetected tumour growth.
      This study highlights the important factors to be considered when deciding a safe
      time to commence EWA.

PMID- 24038734
TI  - Genome-wide analysis of miRNA-mRNA interactions in marrow stromal cells.
AB  - Regulation of hematopoietic stem cell proliferation, lineage commitment, and
      differentiation in adult vertebrates requires extrinsic signals provided by cells
      in the marrow microenvironment (ME) located within the bone marrow. Both secreted
      and cell-surface bound factors critical to this regulation have been identified,
      yet control of their expression by cells within the ME has not been addressed.
      Herein we hypothesize that microRNAs (miRNAs) contribute to their controlled
      expression. MiRNAs are small noncoding RNAs that bind to target mRNAs and
      downregulate gene expression by either initiating mRNA degradation or preventing
      peptide translation. Testing the role of miRNAs in downregulating gene expression
      has been difficult since conventional techniques used to define miRNA-mRNA
      interactions are indirect and have high false-positive and negative rates. In
      this report, a genome-wide biochemical technique (high-throughput sequencing of
      RNA isolated by cross-linking immunoprecipitation or HITS-CLIP) was used to
      generate unbiased genome-wide maps of miRNA-mRNA interactions in two critical
      cellular components of the marrow ME: marrow stromal cells and bone marrow
      endothelial cells. Analysis of these datasets identified miRNAs as direct
      regulators of JAG1, WNT5A, MMP2, and VEGFA; four factors that are important to ME
      function. Our results show the feasibility and utility of unbiased genome-wide
      biochemical techniques in dissecting the role of miRNAs in regulation of complex
      tissues such as the marrow ME.

PMID- 24038737
TI  - Base-catalyzed electrophilic trifluoromethylthiolation of terminal alkynes.

PMID- 24038736
TI  - Outcome of patients with Stage II/favorable histology Wilms tumor with and
      without local tumor spill: a report from the National Wilms Tumor Study Group.
AB  - BACKGROUND: Intra-operative tumor spill increases the risk of local recurrence of
      Wilms tumor, and adversely impacts relapse-free (RFS) and overall survival (OS)
      rates. METHODS: Surgical checklists, operative notes, institutional pathology
      reports, central pathology review and flow sheets of 602 patients registered
      between August 1986 and September 1994 on National Wilms Tumor Study-4 as
      randomized, followed or switched and coded as Final Stage II, favorable histology
      (FH) were reviewed. RFS and OS were estimated using the Kaplan-Meier method.
      Hazard ratios (HRs) were estimated using the Cox model and tested for statistical
      significance by the log-rank test. RESULTS: Four hundred ninety-nine patients
      were found after review to have Stage II, FH Wilms tumor. The 8-year RFS
      percentages were 85.0% (95% confidence interval (CI): 81.1%, 88.1%) for those
      with no spill compared to 75.7% (65.8%, 83.2%) for those with spill. The 8-year
      OS percentages were 95.6% (93.1%, 97.3%) for those with no spill compared to
      90.3% (82.2%, 94.9%) for those with spill. The HR for relapse among those with
      spill was 1.55 ((95%CI: 0.97,2.51), P = 0.067) and the HR for death was 1.94
      ((0.92,4.09), P = 0.077). CONCLUSIONS: RFS and OS were lower for patients who had
      intra-operative tumor spill. The majority of NWTS Stage II, FH patients with
      intra-operative tumor spill have an overall excellent outcome when treated with
      two drug chemotherapy (vincristine and actinomycin D) and no abdominal
      irradiation.

PMID- 24038738
TI  - Increasing the structural span of alkyne metathesis.
AB  - A new generation of alkyne metathesis catalysts, which are distinguished by high
      activity and an exquisite functional group tolerance, allows the scope of this
      transformation to be extended beyond its traditional range. They accept
      substrates that were previously found problematic or unreactive, such as
      propargyl alcohol derivatives, electron-deficient and electron-rich acetylenes of
      various types, and even terminal alkynes. Moreover, post-metathetic
      transformations other than semi-reduction increase the structural portfolio, as
      witnessed by the synthesis of a annulated phenol derivative via ring-closing
      alkyne metathesis (RCAM) followed by a transannular gold-catalyzed Conia-ene
      reaction. Further examples encompass a post-metathetic transannular ketone-alkyne
      cyclization with formation of a trisubstituted furan, a ruthenium-catalyzed redox
      isomerization, and a Meyer-Schuster rearrangement/oxa-Michael cascade. These
      reaction modes fueled model studies toward salicylate macrolides,
      furanocembranolides, and the cytotoxic macrolides acutiphycin and enigmazole A;
      moreover, they served as the key design elements of concise total syntheses of
      dehydrocurvularin (27) and the antibiotic agent A26771B (36). 

PMID- 24038741
TI  - Justification for routine intensive care after liver transplantation.

PMID- 24038739
TI  - Multi-institutional investigation of the prognostic value of lymph nodel yield in
      advanced-stage oral cavity squamous cell carcinoma.
AB  - BACKGROUND: Although existing literature provides surgical recommendations for
      treating occult disease (cN0) in early-stage oral cavity squamous cell carcinoma
      (SCC), a focus on late-stage oral cavity SCC is less pervasive. METHODS: The
      medical records of 162 patients with late-stage oral cavity SCC pN0 who underwent
      primary neck dissections were reviewed. Lymph node yield as a prognosticator was
      examined. RESULTS: Despite being staged pN0, patients that had a higher lymph
      node yield had an improved regional/distant control rates, disease-free survival
      (DFS), disease-specific survival (DSS), and overall survival (OS). Lymph node
      yield consistently outperformed all other standard variables as being the single
      best prognostic factor with a tight risk ratio range (RR = 0.95-0.98) even when
      correcting for the number of lymph nodes examined. CONCLUSION: The results of
      this study showed that lower regional recurrence rates and improved survival
      outcomes were seen as lymph node yield increased for advanced T classification
      oral cavity SCC pN0. This suggests that increasing lymph node yield with an
      extended cervical lymphadenectomy may result in lower recurrence rates and
      improved survival outcomes for this advanced stage group.

PMID- 24038740
TI  - Borderline trend towards long-term mortality benefit from drug eluting stents
      implantation in ST-elevation myocardial infarction patients in Poland-data from
      NRDES registry.
AB  - OBJECTIVES: To analyze long-term outcome of ST-Elevation Myocardial Infarction
      (STEMI) and non-STEMI (NSTEMI) patients treated with Drug Eluting Stents (DES)
      stents with regard to mortality and stent thrombosis rates based on the national
      Polish PCI registry database. BACKGROUND: Only a few studies suggested potential
      trend towards lower mortality in STEMI patients treated with DES. Current
      European Society of Cardiology STEMI guidelines recommend DES use only with one
      restriction to suspected patient poor compliance or contraindication to dual
      antiplatelet therapy. METHODS: Thirteen high-volume interventional cardiology
      centers in Poland enrolled patients in National Registry of Drug Eluting Stents
      (NRDES) Registry from October 2010 till October 2011. RESULTS: There were 2686
      patients enrolled in NRDES Registry. Eighty five patients (3%) had both DES and
      BMS implanted at index PCI procedure and were excluded from further analysis. A
      subpopulation of STEMI (1709; 66%) and NSTEMI (892; 34%) patients was selected
      for BMS vs DES comparison. A significant difference in favor of DES group for 1
      year mortality was found in STEMI subgroup (P < 0.0001-unadjusted and P = 0.0497
      after propensity score adjustment). No such differences were noticed for NSTEMI
      subgroup or stent thrombosis comparisons. CONCLUSIONS: A strong selection bias
      for DES stents was observed with regard to demographic and angiographic
      characteristics in both STEMI and NSTEMI. DES implantation was associated with
      similar ischemic outcome to BMS at 1-year follow-up. STEMI patients with DES
      presented a trend towards lower long-term mortality at 1 year in comparison to
      BMS.

PMID- 24038742
TI  - Validation of anaphylaxis in the Food and Drug Administration's Mini-Sentinel.
AB  - PURPOSE: We aim to develop and validate the positive predictive value (PPV) of an
      algorithm to identify anaphylaxis using health plan administrative and claims
      data. Previously published PPVs for anaphylaxis using International
      Classification of Diseases, ninth revision, Clinical Modification (ICD-9-CM)
      codes range from 52% to 57%. METHODS: We conducted a retrospective study using
      administrative and claims data from eight health plans. Using diagnosis and
      procedure codes, we developed an algorithm to identify potential cases of
      anaphylaxis from the Mini-Sentinel Distributed Database between January 2009 and
      December 2010. A random sample of medical charts (n = 150) was identified for
      chart abstraction. Two physician adjudicators reviewed each potential case. Using
      physician adjudicator judgments on whether the case met diagnostic criteria for
      anaphylaxis, we calculated a PPV for the algorithm. RESULTS: Of the 122 patients
      for whom complete charts were received, 77 were judged by physician adjudicators
      to have anaphylaxis. The PPV for the algorithm was 63.1% (95%CI: 53.9-71.7%),
      using the clinical criteria by Sampson as the gold standard. The PPV was highest
      for inpatient encounters with ICD-9-CM codes of 995.0 or 999.4. By combining only
      the top performing ICD-9-CM codes, we identified an algorithm with a PPV of
      75.0%, but only 66% of cases of anaphylaxis were identified using this modified
      algorithm. CONCLUSIONS: The PPV for the ICD-9-CM-based algorithm for anaphylaxis
      was slightly higher than PPV estimates reported in prior studies, but remained
      low. We were able to identify an algorithm that optimized the PPV but
      demonstrated lower sensitivity for anaphylactic events.

PMID- 24038744
TI  - Integrated strategy for improving functional connectivity mapping using multiecho
      fMRI.
AB  - Functional connectivity analysis of resting state blood oxygen level-dependent
      (BOLD) functional MRI is widely used for noninvasively studying brain functional
      networks. Recent findings have indicated, however, that even small (<=1 mm)
      amounts of head movement during scanning can disproportionately bias connectivity
      estimates, despite various preprocessing efforts. Further complications for
      interregional connectivity estimation from time domain signals include the
      unaccounted reduction in BOLD degrees of freedom related to sensitivity losses
      from high subject motion. To address these issues, we describe an integrated
      strategy for data acquisition, denoising, and connectivity estimation. This
      strategy builds on our previously published technique combining data acquisition
      with multiecho (ME) echo planar imaging and analysis with spatial independent
      component analysis (ICA), called ME-ICA, which distinguishes BOLD (neuronal) and
      non-BOLD (artifactual) components based on linear echo-time dependence of signals
      a characteristic property of BOLD T*2 signal changes. Here we show for 32 control
      subjects that this method provides a physically principled and nearly operator
      independent way of removing complex artifacts such as motion from resting state
      data. We then describe a robust estimator of functional connectivity based on
      interregional correlation of BOLD-independent component coefficients. This
      estimator, called independent components regression, considerably simplifies
      statistical inference for functional connectivity because degrees of freedom
      equals the number of independent coefficients. Compared with traditional
      connectivity estimation methods, the proposed strategy results in fourfold
      improvements in signal-to-noise ratio, functional connectivity analysis with
      improved specificity, and valid statistical inference with nominal control of
      type 1 error in contrasts of connectivity between groups with different levels of
      subject motion.

PMID- 24038745
TI  - Rhabdopeptides as insect-specific virulence factors from entomopathogenic
      bacteria.
AB  - Six novel linear peptides, named "rhabdopeptides", have been identified in the
      entomopathogenic bacterium Xenorhabdus nematophila after the discovery of the
      corresponding rdp gene cluster by using a promoter trap strategy for the
      detection of insect-inducible genes. The structures of these rhabdopeptides were
      deduced from labeling experiments combined with detailed MS analysis. Detailed
      analysis of an rdp mutant revealed that these compounds participate in virulence
      towards insects and are produced upon bacterial infection of a suitable insect
      host. Furthermore, two additional rhabdopeptide derivatives produced by
      Xenorhabdus cabanillasii were isolated, these showed activity against insect
      hemocytes thereby confirming the virulence of this novel class of compounds. 

PMID- 24038743
TI  - Structure and stability of the C-terminal helical bundle of the E. coli
      mechanosensitive channel of large conductance.
AB  - The crystal structure of the cytoplasmic domain (CTD) from the mechanosensitive
      channel of large conductance (MscL) in E. coli has been determined at 1.45 A
      resolution. This domain forms a pentameric coiled coil similar to that observed
      in the structure of MscL from M. tuberculosis and also found in the cartilage
      oligomeric matrix protein (COMPcc). It contains canonical hydrophobic and
      atypical ionic interactions compared to previously characterized coiled coil
      structures. Thermodynamic analysis indicates that while the free EcMscL-CTD is
      less stable than other coiled coils, it is likely to remain folded in context of
      the full-length channel. 

PMID- 24038746
TI  - Robotic retroperitoneal approach - a new technique for the upper urinary tract
      and adrenal gland.
AB  - BACKGROUND: The retroperitoneal approach is generally avoided because of the
      reduced working space, the difficulties in robot positioning and the risk of arms
      conflict. A new robotic retroperitoneal approach is presented that can be applied
      for upper urinary tract pathology and adrenal pathology. METHODS: Between
      November 2009 and November 2011, 34 out of 114 robotic procedures were performed
      by the retroperitoneal approach using a triangle shaped trocar placement and the
      robotic cart positioned at the patient's head. RESULTS: All of the 34
      retroperitoneal procedures were performed using this type of approach, with no
      conflict between the robotic arms and no conversions. The average operating time
      was 50 min for simple nephrectomies and 180 min for partial nephrectomies. The
      blood loss was not relevant. CONCLUSION: This approach enables excellent mobility
      for the robotic arms, generating no conflict and providing good maneuvering space
      for the bedside assistant.

PMID- 24038747
TI  - Out of sight, out of mind? a review of data available on the health of care home
      residents in longitudinal and nationally representative cross-sectional studies
      in the UK and Ireland.
AB  - BACKGROUND: care home residents are aged, many have multiple co-morbidities and
      low levels of functioning. Yet, the UK has no routinely available, national data
      on health in care homes. The aim of this study is to identify longitudinal or
      nationally representative cross-sectional sources of information on the health
      and wellbeing of older adults residing in care homes in the UK and Ireland.
      METHODS: searches were made of health databases (Medline, Embase), websites of
      the Economic and Social Data Service and UK Office for National Statistics, and
      selected journals. On-going longitudinal or repeated cross-sectional studies were
      sought in the UK and Ireland, that included participants aged over 65 and
      reported one or more health-related variables. Data were extracted on studies
      that included older adults in care homes. If necessary, study teams were
      contacted for information. RESULTS: we identified 42 longitudinal cohort or
      repeated cross-sectional studies in the UK that involved older adults. Of these,
      17 studies provided data from care home residents. The time period of data
      collection ranged from 2 to 40 years. Proxy interviews were used to capture the
      majority of data in care homes. CONCLUSION: in the UK and Ireland, most
      longitudinal and nationally representative cross-sectional studies do not include
      or follow-up older adults in care homes. Systematic data collection on the health
      of older adults in care homes should be a priority, to inform policy development
      and enable monitoring of care delivery and health outcomes.

PMID- 24038748
TI  - Depression, anxiety, and somatic symptoms in older cancer patients: a comparison
      across age groups.
AB  - BACKGROUND: Previous studies have reported that older cancer patients experience
      lower psychological distress than younger patients, but most prior studies do not
      differentiate between age groups within the 'older' category. AIM: The aim of
      this study was to assess the intensity of the symptoms of depression, anxiety,
      and somatic symptoms among different age groups of older cancer patients.
      METHODS: Participants were composed of 321 cancer patients 60 years and older,
      who were divided into three age groups: 60-69, 70-79, and 80+ years. The
      participants answered the Brief Symptom Inventory-18, which included subscales
      for depression, anxiety, and somatic symptoms and the cancer-related problem
      list, in addition to providing personal and cancer-related details. RESULTS:
      Depressive, anxiety, and somatic symptoms and cancer-related problems were lowest
      in the 70-79 years age group and highest in the 80+ years age group. Comparisons
      between pairs of groups showed significant differences between each of the groups
      in Brief Symptom Inventory total scores and between the 80+ years age group and
      the other two groups in regard to depressive symptoms and cancer-related
      problems. Differences, related to anxiety and somatic symptoms, were significant
      for the 70-79 year olds, in comparison with the youngest and oldest groups.
      Intensity of symptoms was explained by older age, higher number of cancer-related
      problems, female gender, and lower income. CONCLUSION: Nonlinear relations exist
      between age and psychological symptoms, which is in line with the postponement of
      age-related health and functional decline in the modern era. These results
      suggest that the study of psychological reactions to cancer should examine
      differences between age groups among older cancer patients.

PMID- 24038751
TI  - Rapid removal of matrices from small-volume samples by step-voltage
      nanoelectrospray.
AB  - Matrix unloaded: By changing from fixed-voltage (left) to step-voltage
      nanoelectrospray (right), the mass-spectrometric analysis of small-volume
      physiological samples is possible. Separation and ionization are achieved in one
      process, which avoids sample loss and dilution and prevents interference by the
      matrix. The result is high sensitivity even for samples at the nanoliter level. 

PMID- 24038750
TI  - Oct4 maintains the pluripotency of human embryonic stem cells by inactivating p53
      through Sirt1-mediated deacetylation.
AB  - Oct4 is critical to maintain the pluripotency of human embryonic stem cells
      (hESCs); however, the underlying mechanism remains to be fully understood. Here,
      we report that silencing of Oct4 in hESCs leads to the activation of tumor
      suppressor p53, inducing the differentiation of hESCs since acute disruption of
      p53 in p53 conditional knockout (p53CKO) hESCs prevents the differentiation of
      hESCs after Oct4 depletion. We further discovered that the silencing of Oct4
      significantly reduces the expression of Sirt1, a deacetylase known to inhibit p53
      activity and the differentiation of ESCs, leading to increased acetylation of p53
      at lysine 120 and 164. The importance of Sirt1 in mediating Oct4-dependent
      pluripotency is revealed by the finding that the ectopic expression of Sirt1 in
      Oct4-silenced hESCs prevents p53 activation and hESC differentiation. In
      addition, using knock-in approach, we revealed that the acetylation of p53 at
      lysine 120 and 164 is required for both stabilization and activity of p53 in
      hESCs. In summary, our findings reveal a novel role of Oct4 in maintaining the
      pluripotency of hESCs by suppressing pathways that induce differentiation.
      Considering that p53 suppresses pluripotency after DNA damage response in ESCs,
      our findings further underscore the stringent mechanism to coordinate DNA damage
      response pathways and pluripotency pathways in order to maintain the pluripotency
      and genomic stability of hESCs.

PMID- 24038749
TI  - Topological graph kernel on multiple thresholded functional connectivity networks
      for mild cognitive impairment classification.
AB  - Recently, brain connectivity networks have been used for classification of
      Alzheimer's disease and mild cognitive impairment (MCI) from normal controls
      (NC). In typical connectivity-networks-based classification approaches, local
      measures of connectivity networks are first extracted from each region-of
      interest as network features, which are then concatenated into a vector for
      subsequent feature selection and classification. However, some useful structural
      information of network, especially global topological information, may be lost in
      this type of approaches. To address this issue, in this article, we propose a
      connectivity-networks-based classification framework to identify accurately the
      MCI patients from NC. The core of the proposed method involves the use of a new
      graph-kernel-based approach to measure directly the topological similarity
      between connectivity networks. We evaluate our method on functional connectivity
      networks of 12 MCI and 25 NC subjects. The experimental results show that our
      proposed method achieves a classification accuracy of 91.9%, a sensitivity of
      100.0%, a balanced accuracy of 94.0%, and an area under receiver operating
      characteristic curve of 0.94, demonstrating a great potential in MCI
      classification, based on connectivity networks. Further connectivity analysis
      indicates that the connectivity of the selected brain regions is different
      between MCI patients and NC, that is, MCI patients show reduced functional
      connectivity compared with NC, in line with the findings reported in the existing
      studies.

PMID- 24038752
TI  - Impacts of a spring heat wave on canopy processes in a northern hardwood forest.
AB  - Heat wave frequency, duration, and intensity are predicted to increase with
      global warming, but the potential impacts of short-term high temperature events
      on forest functioning remain virtually unstudied. We examined canopy processes in
      a forest in Central Ontario following 3 days of record-setting high temperatures
      (31-33  degrees C) that coincided with the peak in leaf expansion of dominant
      trees in late May 2010. Leaf area dynamics, leaf morphology, and leaf-level gas
      exchange were compared to data from prior years of sampling (2002-2008) at the
      same site, focusing on Acer saccharum Marsh., the dominant tree in the region.
      Extensive shedding of partially expanded leaves was observed immediately
      following high temperature days, with A. saccharum losing ca. 25% of total leaf
      production but subsequently producing an unusual second flush of neoformed
      leaves. Both leaf losses and subsequent reflushing were highest in the upper
      canopy; however, retained preformed leaves and neoformed leaves showed reduced
      size, resulting in an overall decline in end-of-season leaf area index of 64% in
      A. saccharum, and 16% in the entire forest. Saplings showed lower leaf losses,
      but also a lower capacity to reflush relative to mature trees. Both surviving
      preformed and neoformed leaves had severely depressed photosynthetic capacity
      early in the summer of 2010, but largely regained photosynthetic competence by
      the end of the growing season. These results indicate that even short-term heat
      waves can have severe impacts in northern forests, and suggest a particular
      vulnerability to high temperatures during the spring period of leaf expansion in
      temperate deciduous forests.

PMID- 24038754
TI  - The "old theme" of variability versus transitory phenotypes in thanatophoric
      dysplasia type 1: two 19-week-old fetuses with ("San Diego" variant) and without
      ragged metaphyses due to the same FGFR3 mutation.

PMID- 24038753
TI  - Three-dimensional culture of differentiated endometrial stromal cells to
      oligodendrocyte progenitor cells (OPCs) in fibrin hydrogel.
AB  - Neural tissue engineering is one of the most promising strategies for treatment
      of nerve tissue injuries. Three-dimensional (3D) environment mimics in vivo
      conditions for cells. 3D distribution and growth of the cells within the scaffold
      are both important for neural tissue engineering. In this study, endometrial
      stromal cell-derived oligodendrocyte progenitor cells (EnSC-derived OPCs) were
      cultured in fibrin gel and cell differentiation and viability were evaluated
      after 8 days of post-culture. The structural and mechanical characteristics of
      fibrin gel-like scaffold were examined with rheological analysis. EnSCs were
      isolated from donor tissue and were induced to OPCs with growth factors
      (FGF2/EGF/PDGF-AA) for 12 days, then were cultured in fibrin gel with
      Triiodothyronine (T3) medium for another 8 days. The viability of cells was
      analyzed using MTT assay for a period of 8 days culturing in a fibrin matrix.
      Structure of fibrin matrix and cell morphology was analyzed with SEM. TEM,
      immunostaining and quantitative RT-PCR was performed for OPCs markers after cell
      culturing in fibrin matrix. Cell viability is enhanced in fibrin matrix after 8
      days. SEM and TEM show that cells are in good integration with nano-fibers.
      Moreover, immunohistochemistry and quantitative RT-PCR of OPCs differentiation
      markers showed that Olig2, Sox10, PDGFRa, CNP, and A2B5 are expressed after 8
      days culturing within fibrin matrix. Fibrin can provide a suitable 3-D scaffold
      for EnSCs differentiated cells for the regeneration of CNS. 

PMID- 24038755
TI  - Unwrapping core-shell nanowires into nanoribbon-based superstructures.
AB  - A prize for the ribbons: High-quality crystalline semiconducting nanoribbons can
      be prepared by "unwrapping" core-shell nanowire precursors. For example, Ge
      nanowires were coated with a Si shell and the top surface was carved by etching
      whereas the sides were protected by a thin layer of photoresist material. Finally
      the Ge core was removed selectively by chemical means to give fully opened and
      flat nanoribbon structures. 

PMID- 24038756
TI  - Transcranial Doppler and brain MRI in children with sickle cell disease and high
      hemoglobin F levels.
AB  - BACKGROUND/OBJECTIVE: While overt stroke and silent brain infarcts (SBI) are
      uncommon among Kuwaiti patients with sickle cell disease (SCD), there have been
      no previous transcranial Doppler (TCD) studies in this population. The main
      objective of this study is to determine TCD velocities in a group of Kuwaiti
      children with SCD and correlate same with brain magnetic resonance imaging (MRI)
      and angiography (MRA) findings. MATERIALS AND METHODS: Forty-three steady-state,
      pediatric patients with SCD aged 10.1 +/- 3.9 years (21 SS, 19 Sbeta(0)Thal, and
      3 SD) were studied. Twenty-six age-matched, normal siblings of the patients
      served as controls. TCD was performed using a General Electric (GE), Vivid 3
      equipment and MRI/MRA with a GE Signa Excite HD 1.5 Tesla magnet. Complete blood
      count was with an electronic counter and Hb quantitation with cation-exchange
      high performance liquid chromatography (HPLC). RESULTS: The mean time-averaged
      mean of the maximum velocity (TAMV) was significantly higher in the SCD group
      than the controls, but was normal (<170 cm/second) in all. The mean values were
      comparable among the SS and Sbeta(0)thal groups. Five (11.1%) patients had SBI
      and all were between 12 and 16 years of age. There was no significant difference
      of TAMV in this group compared to those without infarcts. No patient showed
      evidence of stenosis or any other abnormalities in the circle of Willis vessels.
      CONCLUSION: The mild phenotype among Kuwaiti patients with SCD is reflected in
      normal TCD velocities and a low prevalence of SBI in children with the disease.

PMID- 24038757
TI  - A shear stress regulated assembly route to silica nanotubes and their closely
      packed hollow mesostructures.
AB  - Ready to load: A shear stress regulated assembly route has been used to fabricate
      silica nanotubes and hollow mesostructures thereof. The packed silica nanotubes
      were employed as support for loading gold nanoparticles for efficiently
      catalyzing the epoxidation of styrene with high conversion and selectivity
      towards styrene oxide. 

PMID- 24038758
TI  - Space-confinement-induced synthesis of pyridinic- and pyrrolic-nitrogen-doped
      graphene for the catalysis of oxygen reduction.

PMID- 24038759
TI  - Gain of 1q is a marker of poor prognosis in Wilms' tumors.
AB  - Wilms' tumor (WT) trials aim to better tailor treatment intensity to the risk of
      relapse and death. Currently, stage, histology, age (< or > 24 months), and
      combined loss of heterozygosity at 1p and 16q in chemotherapy-naive WTs are the
      only risk factors used for treatment stratification. However, they predict only
      less than one-third of all relapsing patients, implying that other factors are
      involved in treatment failure. Previous studies have associated 1q gain with
      adverse outcome. Therefore, in this study, the role of 1q gain and other common
      cytogenetic aberrations (CAs) in WTs was investigated and related to follow-up
      data from patients with WT treated in the United Kingdom; 19% (64/331) had 1q
      gain. Gain of 1q was significantly associated with 16q loss (P < 0.001) and 1p
      loss (P < 0.001). In multivariate analysis taking account of age, tumor stage,
      anaplasia, and common CA (e.g., 1p loss and 16q loss), 1q gain was independently
      associated with adverse event-free survival [EFS; hazard ratio (HR) = 2.45, P =
      0.02] and overall survival (HR = 4.28, P = 0.004). Loss of 14q was independently
      associated with an adverse EFS (HR = 4.0, P = 0.04). Gain of 1q is a marker of
      poor prognosis in WTs, independent of high tumor stage and anaplasia which remain
      the overarching adverse prognostic factors. Confirmation in other studies is
      necessary before future therapeutic studies can incorporate 1q gain into new risk
      stratification schema.

PMID- 24038760
TI  - Synthetic glycopolypeptides as potential inhibitory agents for dendritic cells
      and HIV-1 trafficking.
AB  - Multivalent binding is a key for many critical biological processes and unique
      recognition and specificity in binding enables many of different glycans and
      proteins to work in a great harmony within the human body. In this study, the
      binding kinetics of synthetic glycopolypeptides to the dendritic cell lectin DC
      SIGN and their inhibition potential for DC-SIGN interactions with the gp120
      envelope glycoprotein of HIV-1 (gp120) are investigated. 

PMID- 24038761
TI  - Surface porosity and roughness of micrographite film for nucleation of
      hydroxyapatite.
AB  - Heterogeneous nucleation of hydroxyapatite (HAp) can be facilitated by physical
      and chemical properties of material surface. In this article, we reported how
      effective surface porosity and roughness are for inducing nucleation of HAp
      crystal in simulated body fluid. Two types of micrographite film (MGF) prepared
      from assembly of micrographite flakes were used as seeds to induce HAp crystal:
      uncompressed (high surface porosity) and compressed (low surface porosity) MGFs.
      Compressed MGF was prepared by applying mechanical compression to the
      uncompressed MGF. Uncompressed and compressed MGFs have similar surface
      wettability with the water contact angles (theta) of 113 degrees  and 107 degrees
      , respectively. The number density of HAp crystals on the uncompressed MGF was
      higher than that of the compressed MGF by a factor of 6. This result implied that
      surface porosity and roughness were more effective parameters for inducing HAp
      crystal than surface wettability. Uncompressed MGF also induced HAp nucleation
      better than a cover glass although the glass had high wettability (theta = 64
      degrees ). The effectiveness of uncompressed MGF on inducing HAp crystals was as
      high as that of the SiO2 -coated Si substrate. Our finding suggests that we do
      not require to functionalize material surface to be an effective seed; a surface
      with pores or roughness of the right scale is enough.

PMID- 24038762
TI  - Post-fracture excessive callus formation in a child on imatinib therapy.

PMID- 24038763
TI  - Haplotype co-segregation with attention deficit-hyperactivity disorder in
      unrelated German multi-generation families.
AB  - Complex disorders have proved to be elusive in the search for underlying genetic
      causes. In the presence of large multi-generation pedigrees with multiple
      affected individuals, heritable familial forms of the disorders can be
      postulated. Observations of particular chromosomal haplotypes shared among all
      affected individuals within pedigrees may reveal chromosomal regions, in which
      the disease-related genes may be located. Hence, the biochemical pathways
      involved in pathogenesis can be exposed. We have recruited eight large Attention
      Deficit-Hyperactivity Disorder (ADHD, OMIM: #143465) families of German descent.
      Densely spaced informative microsatellite markers with high heterozygosity rates
      were used to fine-map and haplotype chromosomal regions of interest in these
      families. In three subsets and one full family of the eight ADHD families,
      haplotypes co-segregating with ADHD-affected individuals were identified at
      chromosomes 1q25, 5q11-5q13, 9q31-9q32, and 18q11-18q21. Positive LOD scores
      supported these co-segregations. The existence of haplotypes co-segregating among
      affected individuals in large ADHD pedigrees suggests the existence of Mendelian
      forms of the disorder and that ADHD-related genes are located within these
      haplotypes. In depth sequencing of these haplotype regions can identify causative
      genetic mechanisms and will allow further insights into the clinico-genetics of
      this complex disorder.

PMID- 24038764
TI  - Sequential moderate coronary artery fistula and moderate coronary artery stenosis
      causing ischemia demonstrated by fractional flow reserve and relieved following
      percutaneous coronary intervention.
AB  - Coronary artery fistulae are rare anomalous connections arising from the coronary
      circulation. We report a case of anterior wall myocardial ischemia caused by the
      combination of sequential coronary-to-pulmonary artery fistula and moderate (50
      60%) stenosis of the left anterior descending coronary artery. Ischemia was
      demonstrated by myocardial stress perfusion imaging as well as fractional flow
      reserve. Percutaneous coronary intervention of the lesion resulted in resolution
      of ischemia.

PMID- 24038765
TI  - Drug-drug interactions in a cohort of hospitalized elderly patients.
AB  - PURPOSE: The aim of this study is to assess the prevalence of patients exposed to
      potentially severe drug-drug interactions (DDIs) at hospital admission and
      discharge and the related risk of in-hospital mortality and adverse clinical
      events, readmission, and all-cause mortality at 3 months. METHODS: This cross
      sectional, prospective study was held in 70 Italian internal medicine and
      geriatric wards. Potentially severe DDIs at hospital admission and discharge;
      risk of in-hospital mortality and of adverse clinical events, readmission, and
      all-cause mortality at 3-month follow-up. RESULTS: Among 2712 patients aged 65
      years or older recruited at hospital admission, 1642 (60.5%) were exposed to at
      least one potential DDI and 512 (18.9%) to at least one potentially severe DDI.
      Among 2314 patients discharged, 1598 (69.1%) were exposed to at least one
      potential DDI and 1561 (24.2%) to at least one potentially severe DDI.
      Multivariate analysis found a significant association with an increased risk of
      mortality at 3 months in patients exposed to at least two potentially severe DDIs
      (Odds ratio 2.62; 95% confidence interval, 1.00-6.68; p = 0.05). Adverse clinical
      events were potentially related to severe DDIs in two patients who died in the
      hospital, in five readmitted, and one who died at 3 months after discharge.
      CONCLUSIONS: Hospitalization was associated with an increase in potentially
      severe DDIs. A significant association was found for mortality at 3 months after
      discharge in patients with at least two potentially severe DDIs. Careful
      monitoring for potentially severe DDIs, especially those created at discharge or
      recently generated, is important to minimize the risk of harm.

PMID- 24038766
TI  - Early allograft dysfunction: causes, recognition, and management.

PMID- 24038767
TI  - Does relational dysfunction mediate the association between anxiety disorders and
      later depression? Testing an interpersonal model of comorbidity.
AB  - BACKGROUND: Anxiety disorders tend to precede onset of comorbid depression.
      Several researchers have suggested a causal role for anxiety in promoting
      depressive episodes, but few studies have identified specific mechanisms. The
      current study proposes an interpersonal model of comorbidity, where anxiety
      disorders disrupt interpersonal functioning, which in turn elevates risk for
      depression. METHODS: At age 15 (T1), 815 adolescents oversampled for maternal
      depression completed diagnostic interviews, social chronic stress interviews, and
      self-report measures. At age 20 (T2), participants repeated all measures and
      reported on self-perceived interpersonal problems. At approximately age 23 (T3),
      a subset of participants (n = 475) completed a self-report depressive symptoms
      measure. RESULTS: Consistent with other samples, anxiety disorders largely
      preceded depressive disorders. Low sociability and interpersonal oversensitivity
      mediated the association between T1 social anxiety disorder and later depression
      (including T2 depressive diagnosis and T3 depressive symptoms), controlling for
      baseline. Interpersonal oversensitivity and social chronic stress similarly
      mediated the association between generalized anxiety disorder before age 15 and
      later depression. CONCLUSIONS: Interpersonal dysfunction may be one mechanism
      through which anxiety disorders promote later depression, contributing to high
      comorbidity rates.

PMID- 24038768
TI  - Irradiation of juvenile, but not adult, mammary gland increases stem cell self
      renewal and estrogen receptor negative tumors.
AB  - Children exposed to ionizing radiation have a substantially greater breast cancer
      risk than adults; the mechanism for this strong age dependence is not known. Here
      we show that pubertal murine mammary glands exposed to sparsely or densely
      ionizing radiation exhibit enrichment of mammary stem cell and Notch pathways,
      increased mammary repopulating activity indicative of more stem cells, and
      propensity to develop estrogen receptor (ER) negative tumors thought to arise
      from stem cells. We developed a mammary lineage agent-based model (ABM) to
      evaluate cell inactivation, self-renewal, or dedifferentiation via epithelial
      mesenchymal transition (EMT) as mechanisms by which radiation could increase stem
      cells. ABM rejected cell inactivation and predicted increased self-renewal would
      only affect juveniles while dedifferentiation could act in both juveniles and
      adults. To further test self-renewal versus dedifferentiation, we used the MCF10A
      human mammary epithelial cell line, which recapitulates ductal morphogenesis in
      humanized fat pads, undergoes EMT in response to radiation and transforming
      growth factor beta (TGFbeta) and contains rare stem-like cells that are Let-7c
      negative or express both basal and luminal cytokeratins. ABM simulation of
      population dynamics of double cytokeratin cells supported increased self-renewal
      in irradiated MCF10A treated with TGFbeta. Radiation-induced Notch concomitant
      with TGFbeta was necessary for increased self-renewal of Let-7c negative MCF10A
      cells but not for EMT, indicating that these are independent processes.
      Consistent with these data, irradiating adult mice did not increase mammary
      repopulating activity or ER-negative tumors. These studies suggest that
      irradiation during puberty transiently increases stem cell self-renewal, which
      increases susceptibility to developing ER-negative breast cancer.

PMID- 24038769
TI  - Twofold unsymmetrical C-H functionalization of PyrDipSi-substituted arenes: a
      general method for the synthesis of substituted meta-halophenols.

PMID- 24038770
TI  - The concerted nature of the cyclization of squalene oxide to the protosterol
      cation.
AB  - Concerted A-C ring formation: A concerted, but highly asynchronous, pathway was
      identified for the formation of rings A-C in the biosynthetic conversion of
      squalene oxide to the prosterol cation, with ring B being formed in the required
      boat conformation. 

PMID- 24038771
TI  - Inertia in an ombrotrophic bog ecosystem in response to 9 years' realistic
      perturbation by wet deposition of nitrogen, separated by form.
AB  - Wet deposition of nitrogen (N) occurs in oxidized (nitrate) and reduced
      (ammonium) forms. Whether one form drives vegetation change more than the other
      is widely debated, as field evidence has been lacking. We are manipulating N form
      in wet deposition to an ombrotrophic bog, Whim (Scottish Borders), and here
      report nine years of results. Ammonium and nitrate were provided in rainwater
      spray as NH4 Cl or NaNO3 at 8, 24 or 56 kg N ha(-1)  yr(-1) , plus a rainwater
      only control, via an automated system coupled to site meteorology. Detrimental N
      effects were observed in sensitive nonvascular plant species, with higher
      cumulative N loads leading to more damage at lower annual doses. Cover responses
      to N addition, both in relation to form and dose, were species specific and
      mostly dependent on N dose. Some species were generally indifferent to N form and
      dose, while others were dose sensitive. Calluna vulgaris showed a preference for
      higher N doses as ammonium N and Hypnum jutlandicum for nitrate N. However, after
      9 years, the magnitude of change from wet deposited N on overall species cover is
      small, indicating only a slow decline in key species. Nitrogen treatment effects
      on soil N availability were likewise small and rarely correlated with species
      cover. Ammonium caused most N accumulation and damage to sensitive species at
      lower N loads, but toxic effects also occurred with nitrate. However, because
      different species respond differently to N form, setting of ecosystem level
      critical loads by N form is challenging. We recommend implementing the lowest
      value of the critical load range where communities include sensitive nonvascular
      plants and where ammonium dominates wet deposition chemistry. In the context of
      parallel assessment at the same site, N treatments for wet deposition showed
      overall much smaller effects than corresponding inputs of dry deposition as
      ammonia. 

PMID- 24038772
TI  - Diagnostic accuracy of three different methods of temperature measurement in
      acutely ill geriatric patients.
AB  - OBJECTIVE: we examined the diagnostic accuracy of different methods of body
      temperature measurement to diagnose infection in geriatric patients presenting to
      the emergency department (ED). METHODS: this observational study was done in
      consecutive patients >=75 years old presenting to the ED. Body temperature was
      determined by tympanal thermometry, temporal artery thermometry and rectal
      temperature measurement. Adjudicated final diagnosis of infection was done by two
      experts including patient history, clinical and laboratory findings as well as
      radiographic studies. RESULTS: a total of 427 patients were included in the data
      analysis (age: 82.7 +/- 5.1 years). Infection was present in 105 patients
      (24.6%). Respiratory rate, heart rate and body temperature were significantly
      higher in patients with infection, blood pressure was lower (P < 0.01). Body
      temperature measured by tympanal and temporal artery thermometry was correlated
      with rectal thermometry. Body temperature was significantly higher in patients
      with infection compared with those without infection independent of the method of
      body temperature measurement (P < 0.001). The diagnostic accuracy for infection
      quantified by the area under curve (AUC) was comparable among rectal [AUC: 0.72
      (95% CI: 0.65-0.80)] and tympanal thermometry [AUC: 0.73 (95% CI: 0.66-0.81)],
      but significantly lower in temporal artery thermometry [AUC: 0.65 (95% CI: 0.57
      0.73; P < 0.001)]. Compared with rectal measurement tympanal thermometry showed a
      higher bias than temporal artery thermometry (0.54 versus 0.03 degrees C), while
      its limits of agreement were more narrow (-0.14 to 1.21 degrees C versus -0.94
      1.01 degrees C). CONCLUSION: diagnostic accuracy for the identification of
      infection was comparable among tympanal and rectal thermometry and lower for
      temporal artery thermometry. Different cut-off points should be used to identify
      infection using tympanal (37.3 degrees C) or rectal (37.9 degrees C) thermometry.
      In general, temperature measurement is an insensitive method to identify
      geriatric patients with infection. Registration number clinicaltrials.com: KSMC
      tempger-1.

PMID- 24038773
TI  - The antimicrobial activity of Sub3 is dependent on membrane binding and cell
      penetrating ability.
AB  - Because of their high activity against microorganisms and low cytotoxicity,
      cationic antimicrobial peptides (AMPs) have been explored as the next generation
      of antibiotics. Although they have common structural features, the modes of
      action of AMPs are extensively debated, and a single mechanism does not explain
      the activity of all AMPs reported so far. Here we investigated the mechanism of
      action of Sub3, an AMP previously designed and optimised from high-throughput
      screening with bactenecin as the template. Sub3 has potent activity against Gram
      negative and Gram-positive bacteria as well as against fungi, but its mechanism
      of action has remained elusive. By using AFM imaging, zeta potential, flow
      cytometry and fluorescence methodologies with model membranes and bacterial
      cells, we found that, although the mechanism of action involves membrane
      targeting, Sub3 internalises inside bacteria at lethal concentrations without
      permeabilising the membrane, thus suggesting that its antimicrobial activity
      might involve both the membrane and intracellular targets. In addition, we found
      that Sub3 can be internalised into human cells without being toxic. As some
      bacteria are able to survive intracellularly and consequently evade host defences
      and antibiotic treatment, our findings suggest that Sub3 could be useful as an
      intracellular antimicrobial agent for infections that are notoriously difficult
      to treat. 

PMID- 24038774
TI  - White matter microstructure correlates of mathematical giftedness and
      intelligence quotient.
AB  - Recent functional neuroimaging studies have shown differences in brain activation
      between mathematically gifted adolescents and controls. The aim of this study was
      to investigate the relationship between mathematical giftedness, intelligent
      quotient (IQ), and the microstructure of white matter tracts in a sample composed
      of math-gifted adolescents and aged-matched controls. Math-gifted subjects were
      selected through a national program based on detecting enhanced visuospatial
      abilities and creative thinking. We used diffusion tensor imaging to assess white
      matter microstructure in neuroanatomical connectivity. The processing included
      voxel-wise and region of interest-based analyses of the fractional anisotropy
      (FA), a parameter which is purportedly related to white matter microstructure. In
      a whole-sample analysis, IQ showed a significant positive correlation with FA,
      mainly in the corpus callosum, supporting the idea that efficient information
      transfer between hemispheres is crucial for higher intellectual capabilities. In
      addition, math-gifted adolescents showed increased FA (adjusted for IQ) in white
      matter tracts connecting frontal lobes with basal ganglia and parietal regions.
      The enhanced anatomical connectivity observed in the forceps minor and splenium
      may underlie the greater fluid reasoning, visuospatial working memory, and
      creative capabilities of these children.

PMID- 24038775
TI  - Attitudes of young patients with breast cancer toward fertility loss related to
      adjuvant systemic therapies. EORTC study 10002 BIG 3-98.
AB  - OBJECTIVE: Infertility due to anticancer treatments is a major source of distress
      for young patients with cancer. A survey was performed among breast cancer
      patients younger than 35 years, to evaluate the acceptance of chemotherapy in the
      context of infertility risk. METHODS: After obtaining written informed consent,
      we asked 400 premenopausal, early stage breast cancer patients aged <=35 years to
      complete a short, previously pilot-tested questionnaire. Three hundred and eighty
      nine patients were evaluable. The association between the explanatory variables
      and the outcome variables was assessed using logistic regression. RESULTS: Two
      hundred and twenty-eight (59%) participants wanted to have (more) children in the
      future, whereas 158 (41%) did not. Fifty-seven (36%) of the latter did not want
      additional children because of fear of cancer recurrence. Thirty-two women (8%)
      stated they would not accept chemotherapy should it reduce their fertility. This
      was dependent upon already having children, the wish to have (further) children,
      geographical area, disease stage, and already planned chemotherapy. One hundred
      and seventy-one women who would agree to chemotherapy (48%) would accept a risk
      of infertility of 76-100%. This acceptance was dependent on already having
      children and the wish to have (more) children. Of the 355 participants (91%)
      accepting chemotherapy, 48 would accept it only for >=20% gain in cure.
      CONCLUSION: For the majority of young patients with breast cancer, cure remains
      their first priority; for this, they are willing to accept a considerable
      decrease in future fertility, and only less than 10% will forego chances of cure
      to preserve fertility.

PMID- 24038776
TI  - Phenotypic detection of mecC-MRSA: cefoxitin is more reliable than oxacillin.
AB  - OBJECTIVES: To investigate the reliability of cefoxitin and oxacillin for the
      detection of mecC-positive Staphylococcus aureus. METHODS: The susceptibility to
      cefoxitin and oxacillin of 62 mecC-positive S. aureus isolates was investigated
      using broth microdilution, agar dilution, Etest and disc diffusion on different
      types of media. The data were interpreted for the utility of cefoxitin and
      oxacillin in conjunction with the stated methodologies for the detection of mecC
      positive isolates. RESULTS: Cefoxitin with Mueller-Hinton media from Becton
      Dickinson and Oxoid detected all mecC-positive isolates when tested by broth
      microdilution, agar dilution and disc diffusion. By Etest, one isolate was
      falsely susceptible. Mueller-Hinton agar from bioMerieux was substantially less
      able to detect these isolates. One isolate was falsely susceptible by agar
      dilution when using Iso-Sensitest and Columbia agar. Disc diffusion using
      cefoxitin on Iso-Sensitest agar missed 29% of the isolates. For oxacillin, only
      agar dilution on Columbia agar + 2% NaCl was able to detect all mecC-positive
      isolates successfully. CONCLUSIONS: Cefoxitin used with EUCAST methodology and
      oxacillin used with agar dilution on Columbia agar + 2% NaCl detected all mecC
      positive isolates. These methods with their concomitant agars should be preferred
      over Iso-Sensitest, which is recommended by the BSAC. It should be noted that for
      disc diffusion Mueller-Hinton media from bioMerieux performed poorly, with 26%
      47% of mecC isolates being falsely susceptible.

PMID- 24038778
TI  - Three-dimensional macroscopic assemblies of low-dimensional carbon nitrides for
      enhanced hydrogen evolution.
AB  - Simple organic cooperative assembly of triazine molecules leads to three
      dimensional macroscopic assemblies of low-dimensional graphitic carbon nitrides
      (g-CNs), for example, nanoparticles, nanotubes, and nanosheets. The approach
      enables the characterization of the cooperative properties and photocatalytic
      activities of low-dimensional g-CN materials in hydrogen evolution reactions from
      water under visible light. 

PMID- 24038777
TI  - Systematic analysis of funding awarded for antimicrobial resistance research to
      institutions in the UK, 1997-2010.
AB  - OBJECTIVES: To assess the level of research funding awarded to UK institutions
      specifically for antimicrobial resistance-related research and how closely the
      topics funded relate to the clinical and public health burden of resistance.
      METHODS: Databases and web sites were systematically searched for information on
      how infectious disease research studies were funded for the period 1997-2010.
      Studies specifically related to antimicrobial resistance, including bacteriology,
      virology, mycology and parasitology research, were identified and categorized in
      terms of funding by pathogen and disease and by a research and development value
      chain describing the type of science. RESULTS: The overall dataset included 6165
      studies receiving a total investment of L2.6 billion, of which L102 million was
      directed towards antimicrobial resistance research (5.5% of total studies, 3.9%
      of total spend). Of 337 resistance-related projects, 175 studies focused on
      bacteriology (40.2% of total resistance-related spending), 42 focused on
      antiviral resistance (17.2% of funding) and 51 focused on parasitology (27.4% of
      funding). Mean annual funding ranged from L1.9 million in 1997 to L22.1 million
      in 2009. CONCLUSIONS: Despite the fact that the emergence of antimicrobial
      resistance threatens our future ability to treat many infections, the proportion
      of the UK infection-research spend targeting this important area is small. There
      are encouraging signs of increased investment in this area, but it is important
      that this is sustained and targeted at areas of projected greatest burden. Two
      areas of particular concern requiring more investment are tuberculosis and
      multidrug-resistant Gram-negative bacteria.

PMID- 24038779
TI  - Mercury azides and the azide of Millon's base.

PMID- 24038780
TI  - Transcriptional activity of transposable elements in coelacanth.
AB  - The morphological stasis of coelacanths has long suggested a slow evolutionary
      rate. General genomic stasis might also imply a decrease of transposable elements
      activity. To evaluate the potential activity of transposable elements (TEs) in
      "living fossil" species, transcriptomic data of Latimeria chalumnae and its
      Indonesian congener Latimeria menadoensis were compared through the RNA
      sequencing mapping procedures in three different organs (liver, testis, and
      muscle). The analysis of coelacanth transcriptomes highlights a significant
      percentage of transcribed TEs in both species. Major contributors are LINE
      retrotransposons, especially from the CR1 family. Furthermore, some particular
      elements such as a LF-SINE and a LINE2 sequences seem to be more expressed than
      other elements. The amount of TEs expressed in testis suggests possible
      transposition burst in incoming generations. Moreover, significant amount of TEs
      in liver and muscle transcriptomes were also observed. Analyses of elements
      displaying marked organ-specific expression gave us the opportunity to highlight
      exaptation cases, that is, the recruitment of TEs as new cellular genes, but also
      to identify a new Latimeria-specific family of Short Interspersed Nuclear
      Elements called CoeG-SINEs. Overall, transcriptome results do not seem to be in
      line with a slow-evolving genome with poor TE activity.

PMID- 24038781
TI  - Computational design of helical peptides targeting TNFalpha.
AB  - Find and bind: A computational strategy for designing single-helical peptides
      that can bind to a target protein was developed. After identification of
      potential helix-binding positions, sequences and binding conformations were
      derived theoretically, and explored by experimental screening. This method was
      successfully applied in designing peptide inhibitors for a therapeutic target,
      tumor necrosis factor-alpha (TNFalpha). 

PMID- 24038782
TI  - A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild
      campomelic dysplasia and small patella syndrome.
AB  - The phenotypic similarities have been demonstrated between non-lethal campomelic
      dysplasia (CD) and small patella syndrome (SPS), in which different genetic
      defects have been identified. We report on a familial case of skeletal dysplasia
      with overlapping phenotype of mild CD and SPS, including defective ischio-pubic
      ossification, elongated femoral neck, hypoplastic patellae, and increased space
      between the first and the second toes (sandal gap). Direct sequencing analysis
      demonstrated a novel missense mutation (p.H169Q) within the coding region of the
      SOX9 gene and negative for TBX4 mutations. Functional analysis of the p.H169Q
      mutant revealed reduced but not fully abolished transactivation capacity of the
      mutated protein. Retained residual SOX9 function might contribute to an extremely
      mild CD phenotype in the present cases. (c) 2013 Wiley Periodicals, Inc. 

PMID- 24038783
TI  - Drug-induced thrombocytopenia in children.
AB  - BACKGROUND: Acute, immune-mediated thrombocytopenia may be caused by many
      different approved drugs as well as by other substances including vaccines,
      complementary and alternative medicines, herbal remedies, nutritional
      supplements, foods and beverages. All causes are described as drug-induced
      thrombocytopenia (DITP). Often the cause is not recognized, resulting in
      recurrent thrombocytopenia and inappropriate treatments. Systematic analysis of
      children (age less than 18 years) with suspected DITP has not been previously
      reported. PROCEDURES: (1) We searched 15 databases to identify articles
      describing children with thrombocytopenia as an adverse effect of drugs and other
      substances. Articles were reviewed to assign levels of evidence for an
      association of the suspected substance with thrombocytopenia. (2) Data from the
      BloodCenter of Wisconsin were reviewed to identify reports of drug-dependent,
      platelet-reactive antibodies in children with suspected DITP. RESULTS: Of 2,191
      articles identified, 242 were selected for review. Seventy-two articles reporting
      74 individual patients and nine groups of patients had evaluable data. Eleven
      individual patients and one group had definite evidence and 40 patients and three
      groups had probable evidence for an association of the suspected substance with
      thrombocytopenia. Thirty-two substances had a definite or probable association
      with thrombocytopenia. During 2008-2012, sera from 91 children with suspected
      DITP were tested and 21 had drug-dependent, platelet-reactive antibodies
      involving six substances. CONCLUSIONS: Drugs and other substances must be
      considered as potential causes of thrombocytopenia. Evidence from published
      reports and data for drug-dependent, platelet-reactive antibodies can help
      clinicians evaluate of children with unexpected thrombocytopenia.

PMID- 24038784
TI  - Emerging synthetic strategies for core cross-linked star (CCS) polymers and
      applications as interfacial stabilizers: bridging linear polymers and
      nanoparticles.
AB  - Core cross-linked star (CCS) polymers become increasingly important in polymer
      science and are evaluated in many value-added applications. However, limitations
      exist to varied degrees for different synthetic methods. It is clear that
      improvement in synthetic efficiency is fundamental in driving this field moving
      even further. Here, the most recent advances are highlighted in synthetic
      strategies, including cross-linking with cross-linkers of low solubility,
      polymerization-induced self-assembly in aqueous-based heterogeneous media, and
      cross-linking via dynamic covalent bonds. The understanding of CCS polymers is
      also further refined to advocate their role as an intermediate between linear
      polymers and polymeric nanoparticles, and their use as interfacial stabilizers is
      rationalized within this context. 

PMID- 24038785
TI  - Nephrolithiasis in pediatric hematopoietic cell transplantation with up to 40
      years of follow-up.
AB  - BACKGROUND: Kidney stones have been reported to occur after childhood cancer, but
      little is known about kidney stones in children following hematopoietic cell
      transplantation (HCT). The objective of this retrospective study was to determine
      risk factors for the development of kidney stones and to describe the prevalence
      among survivors. PROCEDURE: The study included 1,343 childhood HCT patients. Mean
      follow-up was 15.8 (1.0-40.0) years. Patients were treated with total body
      irradiation (TBI) (n = 948) or non-TBI regimens. Methotrexate (MTX) for acute
      graft-versus-host disease (GVHD) prophylaxis was given as long-course (n = 360),
      short-course (n = 626), or none (n = 357). Prednisone for chronic GVHD therapy
      was received by 525 patients. Multivariate Cox regression models were used to
      estimate the hazard ratio (HR) of risk factors associated with kidney stones.
      RESULTS: Kidney stones developed in 51 patients, a median of 9.9 (0.2-29.4) years
      after first HCT, with a 30-year cumulative incidence of 7.4%. Risk factors
      associated with kidney stones were TBI (HR = 2.2; P = 0.03), age at HCT (12-18
      vs. <6 years, HR = 2.7; P = 0.01), MTX (long vs. none, HR = 3.6; P = 0.02), and
      prednisone (HR = 2.2; P = 0.008). Among 868 survivors, the prevalence of a
      history of kidney stones was 4.7%. CONCLUSIONS: Survivors of childhood HCT have
      an increased risk of developing kidney stones.

PMID- 24038786
TI  - 5-Florouracil-loaded poly(lactic acid)-poly(caprolactone) hybrid scaffold:
      potential chemotherapeutic implant.
AB  - Hybrid nanofibers of poly(lactic acid) and polycaprolactone have been developed
      by embedding cancerous drug through electrospinning technique. The composition of
      polymer has been varied to check the compositional effect on properties. The
      quality of nanofibers has been testified through surface morphology, wetting
      properties using contact angle and mechanical strength under uniaxial elongation.
      The compatibility of drug (5-fluorourasil) with matrix fiber has been verified
      using Fourier transform infrared, X-ray diffraction, Raman spectroscopy, and
      differential scanning calorimetry. The drug release study has been performed
      showing greater release in hybrid fibers when compared with pure polymers as a
      result of synergism of two immiscible polymers and quasi-Fickian diffusion
      mechanism in hybrid nanofiber as implants showing compositional effect on drug
      release. A model has been proposed showing faster release of drugs in hybrid
      systems. Biological responses through fluorescence imaging and MTT assay confirm
      the release of drug from hybrid nanofibers showing potential use of hybrid
      scaffolds as chemotherapeutic implant.

PMID- 24038790
TI  - Solvent-free synthesis of microparticles on superamphiphobic surfaces.
AB  - Polymeric and composite microspheres can be synthesized without solvents or
      process liquids by using superamphiphobic surfaces. In this method, the
      repellency of superamphiphobic layers to monomers and polymer melts and the
      extremely low adhesion to particles are taken advantage of. 

PMID- 24038789
TI  - Stromal cell derived factor-1alpha promotes C-Kit+ cardiac stem/progenitor cell
      quiescence through casein kinase 1alpha and GSK3beta.
AB  - A population of c-kit(+) cardiac stem/progenitor cells (CSPC) has been identified
      in the heart and shown to contribute to myocardial regeneration after infarction.
      Previously, we have shown the chemokine, stromal cell derived factor 1alpha
      (SDF1) is necessary for the myocardial response to infarction where chronic
      infusion of the CXCR4 antagonist, AMD3100, exacerbated MI. Notably, AMD3100
      increased CSPC proliferation. The effect of SDF1 on CSPC proliferation was
      further investigated in primary cultures of magnetically sorted c-kit(+) CSPCs.
      SDF1 facilitated CSPC quiescence by blocking cell cycle progression at the G0 to
      G1 transition. SDF1 decreased casein kinase 1alpha (CK1alpha) consequently
      attenuating beta-catenin phosphorylation, destabilization, and degradation.
      Increased levels of beta-catenin with SDF1 were effective, increasing TCF/LEF
      reporter activity. SDF downregulation of CK1alpha was dependent on proteasomal
      degradation and decreased mRNA expression. CK1alpha siRNA knockdown verified SDF1
      dependent CSPC quiescence requires CK1alpha downregulation and stablilization of
      beta-catenin. Conversely, beta-catenin knockdown increased CSPC proliferation.
      SDF1 also increased GSK3beta Y216 phosphorylation responsible for increased
      activity. SDF1 mediated CK1alpha downregulation and increase in GSK3beta activity
      affected cell cycle through Bmi-1 downregulation, increased cyclin D1
      phosphorylation, and decreased cyclin D1 levels. In conclusion, SDF1 exerts a
      quiescent effect on resident c-kit(+) CSPCs by decreasing CK1alpha levels,
      increasing GSK3beta activity, stabilizing beta-catenin, and affecting regulation
      of the cell cycle through Bmi-1 and cyclin D1. SDF1-dependent quiescence is an
      important factor in stem and progenitor cell preservation under basal conditions,
      however, with stress or injury in which SDF1 is elevated, quiescence may limit
      expansion and contribution to myocardial regeneration.

PMID- 24038791
TI  - Habitat manipulation in lowland rice-coconut cropping systems of the Philippines-
      an effective rodent pest management strategy?
AB  - BACKGROUND: Reduction of vegetation height is recommended as a management
      strategy for controlling rodent pests of rice in South-east Asia, but there are
      limited field data to assess its effectiveness. The breeding biology of the main
      pest species of rodent in the Philippines, Rattus tanezumi, suggests that habitat
      manipulation in irrigated rice-coconut cropping systems may be an effective
      strategy to limit the quality and availability of their nesting habitat. The
      authors imposed a replicated manipulation of vegetation cover in adjacent coconut
      groves during a single rice-cropping season, and added artificial nest sites to
      facilitate capture and culling of young. RESULTS: Three trapping sessions in four
      rice fields (two treatments, two controls) adjacent to coconut groves led to the
      capture of 176 R. tanezumi, 12 Rattus exulans and seven Chrotomys mindorensis
      individuals. There was no significant difference in overall abundance between
      crop stages or between treatments, and there was no treatment effect on damage to
      tillers or rice yield. Only two R. tanezumi were caught at the artificial nest
      sites. CONCLUSION: Habitat manipulation to reduce the quality of R. tanezumi
      nesting habitat adjacent to rice fields is not effective as a lone rodent
      management tool in rice-coconut cropping systems.

PMID- 24038792
TI  - Alkene to carbyne: tandem Lewis acid activation and dehydrogenation of a
      molybdenum ethylene complex.
AB  - Carbyne formation: Treatment of a molybdenum ethylene complex with B(C6 F5 )3
      induces ditopic activation of an ethylene ligand and acceptor-assisted ethane
      elimination to generate a novel type of zwitterionic carbyne complex. 

PMID- 24038793
TI  - Genes contributing to subcortical volumes and intellectual ability implicate the
      thalamus.
AB  - It has been shown that brain volume and general intellectual ability are to a
      significant extent influenced by the same genetic factors. Several cortical
      regions of the brain also show a genetic correlation with intellectual ability,
      demonstrating that intellectual functioning is probably represented in a
      heritable distributed network of cortical regions throughout the brain. This
      study is the first to investigate a genetic association between subcortical
      volumes and intellectual ability, taking into account the thalamus, caudate
      nucleus, putamen, globus pallidus, hippocampus, amygdala, and nucleus accumbens
      using an extended twin design. Genetic modeling was performed on a healthy adult
      twin sample consisting of 106 twin pairs and 30 of their siblings, IQ data was
      obtained from 132 subjects. Our results demonstrate that of all subcortical
      volumes measured, only thalamus volume is significantly correlated with
      intellectual functioning. Importantly, the association found between thalamus
      volume and intellectual ability is significantly influenced by a common genetic
      factor. This genetic factor is also implicated in cerebral brain volume. The
      thalamus, with its widespread cortical connections, may thus play a key role in
      human intelligence.

PMID- 24038794
TI  - Synthesis of azepine derivatives by silver-catalyzed [5+2] cycloaddition of gamma
      amino ketones with alkynes.

PMID- 24038795
TI  - Transseptal strategy in retrograde transcatheter valve-in-valve implantation for
      failed surgical aortic bioprosthesis.
AB  - We report a challenging case of transcatheter aortic valve-in-valve implantation
      in an elderly patient with failed surgical bioprosthesis. The transthoracic
      echocardiogram demonstrated a severe stenosis with a peak gradient of 142 mm Hg.
      The patient was a high-risk candidate for reoperative valve replacement;
      therefore, transfemoral implantation of a CoreValve (Medtronic Inc, Minneapolis,
      MN) was decided. During the procedure, we were unable to introduce the delivery
      catheter system across the bioprosthesis due to its poor alignment with the
      aortic annulus and the severity of the stenosis. With strategies involving
      transseptal puncture and externalization of a guidewire in an antegrade manner,
      the CoreValve was successfully positioned and deployed. This case illustrated the
      utility of transseptal strategies in challenging retrograde transcatheter aortic
      valve-in-valve implantation.

PMID- 24038797
TI  - Hypertension analysis of stress reduction using mindfulness meditation and yoga:
      results from the HARMONY randomized controlled trial.
AB  - BACKGROUND: The HARMONY study was a randomized, controlled trial examining the
      efficacy of an 8-week mindfulness-based stress reduction (MBSR) program for blood
      pressure (BP) lowering among unmedicated stage 1 hypertensive participants.
      METHODS: Participants diagnosed with stage 1 hypertension based on ambulatory BP
      were randomized to either immediate treatment of MBSR for 8 weeks or wait-list
      control. Primary outcome analysis evaluated whether change in awake and 24-hour
      ambulatory BP from baseline to week 12 was significantly different between the 2
      groups. A within-group before and after MBSR analysis was also performed.
      RESULTS: The study enrolled 101 adults (38% male) with baseline average 24-hour
      ambulatory BP of 135+/-7.9/82+/-5.8mm Hg and daytime ambulatory BP of 140+/
      7.7/87+/-6.3 mmHg. At week 12, the change from baseline in 24-hour ambulatory BP
      was 0.4+/-6.7/0.0+/-4.9mm Hg for the immediate intervention and 0.4+/-7.8/-0.4+/
      4.6mm Hg for the wait-list control. There were no significant differences between
      intervention and wait-list control for all ambulatory BP parameters. The
      secondary within-group analysis found a small reduction in BP after MBSR compared
      with baseline, a finding limited to female subjects in a sex analysis.
      CONCLUSIONS: MBSR did not lower ambulatory BP by a statistically or clinically
      significant amount in untreated, stage 1 hypertensive patients when compared with
      a wait-list control group. It leaves untested whether MBSR might be useful for
      lowering BP by improving adherence in treated hypertensive participants. CLINICAL
      TRIALS REGISTRATION: NCT00825526.

PMID- 24038796
TI  - Predicting invasion in grassland ecosystems: is exotic dominance the real
      embarrassment of richness?
AB  - Invasions have increased the size of regional species pools, but are typically
      assumed to reduce native diversity. However, global-scale tests of this
      assumption have been elusive because of the focus on exotic species richness,
      rather than relative abundance. This is problematic because low invader richness
      can indicate invasion resistance by the native community or, alternatively,
      dominance by a single exotic species. Here, we used a globally replicated study
      to quantify relationships between exotic richness and abundance in grass
      dominated ecosystems in 13 countries on six continents, ranging from salt marshes
      to alpine tundra. We tested effects of human land use, native community
      diversity, herbivore pressure, and nutrient limitation on exotic plant dominance.
      Despite its widespread use, exotic richness was a poor proxy for exotic dominance
      at low exotic richness, because sites that contained few exotic species ranged
      from relatively pristine (low exotic richness and cover) to almost completely
      exotic-dominated ones (low exotic richness but high exotic cover). Both exotic
      cover and richness were predicted by native plant diversity (native grass
      richness) and land use (distance to cultivation). Although climate was important
      for predicting both exotic cover and richness, climatic factors predicting cover
      (precipitation variability) differed from those predicting richness (maximum
      temperature and mean temperature in the wettest quarter). Herbivory and nutrient
      limitation did not predict exotic richness or cover. Exotic dominance was
      greatest in areas with low native grass richness at the site- or regional-scale.
      Although this could reflect native grass displacement, a lack of biotic
      resistance is a more likely explanation, given that grasses comprise the most
      aggressive invaders. These findings underscore the need to move beyond richness
      as a surrogate for the extent of invasion, because this metric confounds
      monodominance with invasion resistance. Monitoring species' relative abundance
      will more rapidly advance our understanding of invasions. 

PMID- 24038798
TI  - A pilot evaluation on a stress management programme using a combined approach of
      cognitive behavioural therapy (CBT) and complementary and alternative medicine
      (CAM) for elementary school teachers.
AB  - The aim of this study is to explore the efficacy of implementing a stress
      management programme based on a combined approach using cognitive behavioural
      therapy and complementary and alternative medicine for elementary school teachers
      who experienced mild level of stress, anxiety and/or depressive symptoms in Hong
      Kong. A 12-h programme involving cognitive behavioural therapy, self-management,
      relaxation techniques (diaphragmatic breathing and progressive muscle
      relaxation), mindful exercises (qigong and yoga), aromatherapy and acupressure
      was conducted. A quasi-experimental design was used to compare the intervention
      groups (n = 47) with the wait-list control groups (n = 46). The primary outcome
      measures were depression, anxiety and stress. Results indicated that the
      intervention group had significant reduction in depression [(F = 3.93; degrees of
      freedom (df) = 2.90; p = 0.023)], anxiety (F = 3.37; df = 2.90; p = 0.039) and
      stress (F = 3.63; df = 2.89; p = 0.031) when compared with the control group.
      Participants in both groups demonstrated lowered level of salivary cortisol at
      the post-assessment. The pilot results provided preliminary support to the multi
      component stress management programme in relieving affective symptoms of
      teachers. The programme may be considered as an initial strategy to empower
      teachers with the abilities to cope with their affective symptoms. Further
      evaluation using a better designed randomized study with a larger sample size is
      warranted. (word: 198; max.: 200).

PMID- 24038799
TI  - High frequency of intermediate alleles on Huntington disease-associated
      haplotypes in British Columbia's general population.
AB  - Intermediate alleles (27-35 CAG, IAs) for Huntington disease (HD) usually do not
      confer the disease phenotype but are prone to CAG repeat instability.
      Consequently, offspring are at-risk of inheriting an expanded allele in the HD
      range (>=36 CAG). IAs that expand into a new mutation have been hypothesized to
      be more susceptible to instability compared to IAs identified on the non-HD side
      of a family from the general population. Frequency estimates for IAs are limited
      and have largely been determined using clinical samples of HD or related
      disorders, which may result in an ascertainment bias. This study aimed to
      establish the frequency of IAs in a sample of a British Columbia's (B.C.) general
      population with no known association to HD and examine the haplotype of new
      mutation and general population IAs. CAG sizing was performed on 1,600 DNA
      samples from B.C.'s general population. Haplotypes were determined using 22
      tagging SNPs across the HTT gene. 5.8% of individuals were found to have an IA,
      of which 60% were on HD-associated haplotypes. There was no difference in the
      haplotype distribution of new mutation and general population IAs. These findings
      suggest that IAs are relatively frequent in the general population and are often
      found on haplotypes associated with expanded CAG lengths. There is likely no
      difference in the propensity of new mutation and general population IAs to expand
      into the disease range given that they are both found on disease-associated
      haplotypes. These findings have important implications for clinical practice.

PMID- 24038800
TI  - Recurrence of major depressive episodes is strongly dependent on the number of
      previous episodes.
AB  - BACKGROUND: A history of past major depressive episodes (MDEs) is known to be a
      risk factor for future MDEs. Additional information about the relationship
      between past and future episodes would be useful in clinical practice, it is
      therefore important to fully understand the epidemiology of major depression. We
      asked whether the number of previous MDEs is related to the probability of
      recurrence in the general population. METHODS: Data were used from the Canadian
      National Population Health Survey (NPHS) that was repeated every 2 years from
      1994/1995 to 2009/2010 (i.e., nine cycles). Prior year depression was assessed
      with the Composite International Diagnostic Interview Short Form (CIDI-SF). We
      estimated the total number of MDEs in individuals over the first eight cycles and
      examined recurrence in the ninth cycle. These analyses employed a generalized
      linear model (identity link) where recurrence in cycle 9 was the outcome and the
      predictor variables were age, gender, and the number of MDEs in the first eight
      cycles. RESULTS: The risk for recurrence of depression in cycle 9 was found to
      progressively increase with the number of prior episodes, reaching a value of
      greater than 46% when the number of prior episodes was five to eight. Independent
      of this association, the risk of recurrence was greater in younger people and
      women, but the strength of association of these variables was much weaker for
      past episodes. CONCLUSIONS: MDE recurrence strongly depended on the number of
      preceding episodes. Those at highest risk of recurrence can be easily identified
      by their number of past episodes.

PMID- 24038801
TI  - Social problem solving and social performance after a group social skills
      intervention for childhood brain tumor survivors.
AB  - PURPOSE: The aim of this study was to explore the ability of a group social
      skills intervention program for childhood brain tumor survivors to effect two
      steps of the social information processing model: social problem solving and
      social performance. METHODS: Participants were 15 survivors (eight men and seven
      women) aged 7-15 years. The intervention consisted of eight 2-h weekly sessions
      focused on social skills including friendship making. Social problem solving,
      using hypothetical scenarios, was assessed during sessions 1 and 8. Social
      performance was observed during intervention sessions 1, 4, and 8. RESULTS:
      Compared with session 1, significant increases were found in social performance:
      frequency of maintaining eye contact and social conversations with peers over the
      course of the intervention. No significant changes in social problem solving were
      noted. CONCLUSIONS: This pilot study is the first to report improvements related
      to group social skills intervention at the level of observed social performance
      over the course of intervention. The lack of change in social problem solving
      suggests that survivors may possess the social knowledge required for social
      situations but have difficulty enacting social behaviors.

PMID- 24038802
TI  - Analysis of susceptibility loci for nonsyndromic orofacial clefting in a European
      trio sample.
AB  - Nonsyndromic cleft lip with or without cleft palate (NSCL/P), the most common
      type of orofacial clefting, is one of the most frequent congenital defects. Based
      on epidemiological data, NSCL/P can be distinguished from nonsyndromic cleft
      palate only (NSCPO). Both phenotypes have a complex etiology and environmental
      and genetic factors are involved in their development. To date, genome-wide
      association studies have identified 12 genetic factors that increase the risk for
      NSCL/P in Europeans. Six of them have been independently replicated in samples
      derived from the same population. The aim of the present study was to replicate
      the remaining six NSCL/P risk loci in chromosomal regions 1p22.1, 1p36, 3p11.1,
      8q21.3, 15q22.2, and 20q12 in a family-based sample of European descent. Each of
      the top-associated SNPs (single nucleotide polymorphisms) was genotyped in 343
      NSCL/P and 266 NSCPO nuclear trios. Single-marker association analysis in the
      NSCL/P sample showed a significant association with SNP rs742071 (1p36,
      Pcorrected  = 3.74 * 10(-3) ), which is located in the intronic region of PAX7, a
      gene known to be functionally implicated in craniofacial development. Two
      additional loci, 1p22.1 and 20q12, were nominally significant, but did not
      withstand correction for multiple testing. There was no evidence that the NSCL/P
      risk alleles contribute to the etiology of NSCPO, further supporting that these
      two subtypes of orofacial clefting are primarily etiologically distinct.

PMID- 24038803
TI  - An ethical frame for research with immigrant families.
AB  - In this introduction, the editors give an overview of the ways the volume
      addresses the growing individual and institutional calls for increased clarity
      and rigor in methodological, ethical, and practical research policies and
      guidelines for conducting research with immigrant individuals, families, and
      communities. In addition to summarizing the volume's purpose, background on the
      U.S. immigrant population is given, followed by delineation of the five major
      issues contributing to the field of immigrant studies research and entering the
      "field" and engaging with immigrant families and communities: heterogeneity and
      history, documentation status, research pragmatics, research lens and bias, and
      influence on policy.

PMID- 24038804
TI  - Taking perspective: context, culture, and history.
AB  - There are important lessons to be learned from taking a comparative perspective
      in considering migration. Comparative examination of immigration experiences
      provides a way to glean common denominators of adaptation while considering the
      specificity of sending and receiving contexts and cultures. Equally important is
      a historical perspective that provides a way for us to consider how we may have
      gone through similar travails in the past while recognizing that we face
      particular challenges in this moment.

PMID- 24038805
TI  - Theoretical, methodological, and ethical challenges to the study of immigrants:
      perils and possibilities.
AB  - Research on immigrant communities has often been reductionist, stereotypical, and
      simplistic, and even the most well-intentioned researchers are susceptible to
      using cultural deficit models. This chapter critically evaluates some of the
      dominant tensions and problem areas with respect to researching immigrant
      communities. Specifically, we analyze three primary challenges that researchers
      encounter: the heterogeneity of immigrant lives, adequate representations of
      immigrant communities, and researcher privilege. In addition to identifying these
      unique theoretical, methodological, and ethical concerns, we draw from critical
      theory, feminist scholarship, and cultural psychology to provide an
      interdisciplinary solution. For researchers investigating immigrant communities,
      we advocate the following: (a) grounding of intersectional frameworks; (b)
      reliance on a risk and resilience framework; (c) phenomenological understanding
      of immigrants' everyday lives; (d) inclusion of immigrant participants' voices;
      and (e) cultivation of negative capability. Finally, we briefly review selected
      studies that address three recurring challenges that researchers face and heed
      our five recommendations.

PMID- 24038806
TI  - Doing no harm and getting it right: guidelines for ethical research with
      immigrant communities.
AB  - This chapter provides a guide to research logistics and ethics in studying
      immigrant families. The authors outline major pragmatic issues in research design
      and data collection to which all scholars must attend, although current practices
      often do not respond to the idiosyncratic issues related to vulnerable immigrant
      populations (e.g., undocumented immigrants). The chapter presents vital
      procedures to ensure both the protection of research participants from immigrant
      backgrounds and validity of the data collected from them and seeks to be a source
      of reference for institutional review boards (IRBs). Specific issues addressed
      include navigating IRBs, informed consent, recruitment and sampling, and
      translation of instruments and interviews.

PMID- 24038807
TI  - Undocumented status: implications for child development, policy, and ethical
      research.
AB  - Nearly 5.5 million children in the United States grow up in the shadows of
      undocumented status. We review the ecological domains of influence in children's
      and adolescents' lives and briefly consider health, cognitive, socioemotional,
      educational, and labor market outcomes ripe for study. We also reflect upon the
      ethical policy implications of this growing demographic group and consider
      research strategies in conducting ethical research with this population.

PMID- 24038808
TI  - Sensitive subjects: research choices and presentational challenges in studying
      immigrant children and families.
AB  - We write from our own experience as researchers on the integration of immigrants
      and their children, describing several ethical and research considerations that
      we addressed. In one study we examined the use of public benefits among immigrant
      families. This study posed issues regarding the selection of which "benefits"
      should be considered as "welfare"; how to construct comparison groups of
      immigrants versus natives; and the political sensitivities in reporting widely
      high use rates of certain benefits, particularly Medicaid. A second study
      examined the effects of parental detention and deportation on children. It raised
      issues regarding identifying samples of immigrants to interview, creating trust
      with interviewees and protecting their confidentiality, and examining the views
      not just of advocates and families but others involved in the process (such as
      law enforcement officials) to ensure their perspectives were reflected in
      resulting reports. A third project examined the young children of Black
      immigrants--a group that varies widely in their modes of entry, recency of
      arrival, and levels of human capital. To avoid simplistic misinterpretations, we
      disaggregated data by national origin where possible and ensured that the results
      highlight both the risks and protective factors identified.

PMID- 24038809
TI  - Upregulated expression of microRNA-214 is linked to tumor progression and adverse
      prognosis in pediatric osteosarcoma.
AB  - BACKGROUND: MicroRNA-214 (miR-214) expression has been demonstrated to be
      dysregulated in human malignancies and to play various roles in tumor
      progression. While previous study of miRNA expression profiling found that it was
      one of the most upregulated miRNAs in osteosarcoma signature, the potential role
      of miR-214 in osteosarcomas has been unclear. Therefore, the aim of this study
      was to investigate association of miR-214 expression with clinicopathologic
      features and prognosis in pediatric patients with osteosarcoma. PROCEDURE:
      Quantitative real-time reverse transcriptase-polymerase chain reaction analysis
      was performed to detect expression levels of miR-214 in cancerous and
      noncancerous bone tissues from 92 children treated for primary osteosarcomas.
      Then, the clinical significance of miR-214 dysregulation in pediatric
      osteosarcomas was also determined. RESULTS: Compared with noncancerous bone
      tissues, the expression levels of miR-214 were significantly upregulated in
      osteosarcoma tissues (P < 0.001). High miR-214 expression occurred more
      frequently in osteosarcoma tissues with large tumor size (P = 0.01), positive
      metastasis (P = 0.001) and poor response to pre-operative chemotherapy (P =
      0.006). Moreover, high miR-214 expression was significantly associated with both
      shorter overall (P < 0.001) and progression-free survival (PFS; P = 0.001).
      Multivariate analysis by the Cox proportional hazard model further confirmed that
      high miR-214 expression was an independent prognostic factor of unfavorable
      survival in pediatric osteosarcoma (for overall survival: P = 0.008; for PFS: P =
      0.01). CONCLUSION: Our data offer evidence that upregulated expression of miR-214
      may be linked to tumor progression and adverse prognosis in pediatric
      osteosarcoma. Further investigation in prospective studies would appear
      warranted.

PMID- 24038810
TI  - Versatile substrates and probes for IgA1 protease activity.
AB  - Bacterial meningitis is a severe infectious disease with high mortality. Gram
      positive and Gram-negative bacteria that cause meningitis secrete immunoglobulin
      A1 (IgA1) proteases to assist in mucosal colonization, invasion, and immune
      evasion. IgA1 proteases have unique selectivity, with few reported substrates
      other than IgA1 from human tissue. Here we describe the design, characterization,
      and application of peptide substrates for diverse IgA1 proteases from Neisseria,
      Haemophilus, and Streptococcus bacteria. IgA1 proteases from diverse strains
      showed unexpected selectivity profiles among peptide substrates derived from
      autoproteolytic sites. A fluorescence probe derived from one of these peptides
      was used to quantitate IgA1 protease activity in buffer and in human
      cerebrospinal fluid; it was able to detect recombinant Haemophilus influenzae
      type 1 IgA1 protease at less than 1 MUg mL(-1) . We also used the probe to
      establish the first high-throughput screen for IgA1 protease inhibitors. This
      work provides tools that will help investigate the roles of IgA1 proteases in
      bacterial colonization, immune evasion, and infection. 

PMID- 24038811
TI  - Synthesis of trisubstituted alkenylstannanes through copper-catalyzed three
      component coupling of alkylboranes, alkynoates, and tributyltin methoxide.
AB  - A versatile route to trisubstituted alkenylstannanes is presented. The alkyl and
      Sn moieties were introduced at the beta and alpha carbon atoms of alkynoates,
      respectively, in a formal syn addition mode with complete regioselectivity. A
      variety of functional groups were tolerated in the alkylboranes and alkynoates. 

PMID- 24038813
TI  - Nervous systems in 3D: a comparison of Caridean, anomuran, and brachyuran zoea-I
      (Decapoda).
AB  - Using serial semi-thin sections and digital 3D-reconstructions we studied the
      nervous systems of zoea-I larvae in three decapod species, Hippolyte inermis
      (Leach, 1815), Porcellana platycheles (Pennant, 1777), and Pachygrapsus
      marmoratus (Fabricius, 1787). These taxa represent three decapod lineages, that
      is, Caridea, Anomura, and Brachyura, each characterized by specific zoea-I
      morphology. Special attention was paid to development of ganglia, neuropil
      composition, and segmental nerves. In all zoeae studied, the overall elements,
      for example, the segmental ganglia, their neuropils and most of the nerves of the
      adult decapod nervous system are present. Ongoing differentiation processes are
      observable as well, most obvious in segments with well-developed limbs the
      ganglia are in a more advanced stage of differentiation and more voluminous
      compared to segments with only limb buds or without externally visible limb
      anlagen. Intra- and interspecific comparisons indicate that neuromere
      differentiation thus deviates from a simple anterior-posterior gradient as, for
      example, posterior thoracic neuromeres are less developed than those of the
      pleon. In addition, the differences in the progress of the development of ganglia
      between the studied taxa can best be attributed to heterochronic mechanisms.
      Taxon and stage-specific morphologies indicate that neuronal architecture
      reflects both, morphogenesis to the adult stage and specific larval adaptions,
      and provides sets of characters relevant to understanding the corresponding
      phylogeny.

PMID- 24038812
TI  - Preclinical evaluation of the PARP inhibitor, olaparib, in combination with
      cytotoxic chemotherapy in pediatric solid tumors.
AB  - BACKGROUND: Poly(ADP-ribose) polymerase (PARP) signals DNA damage and facilitates
      DNA repair. PARP inhibitors are being evaluated in cancers with defective DNA
      repair mechanisms or in combination with cytotoxic therapy or radiation. We
      evaluated the PARP inhibitor, olaparib, in combination with chemotherapy using in
      vitro and in vivo pediatric solid tumor models. PROCEDURE: The IC50 of olaparib
      alone and in combination with cytotoxic agents was determined in 10 pediatric
      solid tumor cell lines. Synergy was assessed using the combination index of Chou
      Talalay. Olaparib alone and in combination with topotecan/cyclophosphamide was
      evaluated in xenograft models of Ewing sarcoma (RD-ES) and neuroblastoma (NGP).
      PAR activity was evaluated in cell lines and tumor lysates. RESULTS: Olaparib
      induced growth inhibition, median (range) IC50 = 3.6 (1-33.8) uM, and inhibited
      PAR activity in pediatric solid tumor cell lines. The addition of olaparib to DNA
      damaging agents resulted in additive to synergistic interactions. In RD-ES and
      NGP xenografts, olaparib inhibited PAR activity by 88-100% as a single agent and
      100% when administered with cyclophosphamide/topotecan. Although the addition of
      olaparib did not antagonize the activity of cyclophosphamide/topotecan, clear
      evidence of synergy could not be demonstrated. CONCLUSIONS: In pediatric solid
      tumor cell lines, clinically achievable concentrations of single agent olaparib
      caused growth inhibition. Although the in vitro data demonstrated synergistic
      efficacy of olaparib when added to the camptothecins and alkylating agents,
      synergy was not discernible in vivo. Clinical trials of PARP inhibitors in
      combination DNA damaging agents are necessary to establish the role of PARP
      inhibitors in childhood cancer.

PMID- 24038815
TI  - A nucleobase analogue that pairs strongly with adenine.

PMID- 24038814
TI  - Comparing schizophrenia symptoms in the Iban of Sarawak with other populations to
      elucidate clinical heterogeneity.
AB  - INTRODUCTION: The symptom profile of schizophrenia can vary between ethnic
      groups. We explored selected symptom variables previously reported to be
      characteristic of schizophrenia in the Iban of Sarawak in transethnic populations
      from Australia, India, and Sarawak, Malaysia. We tested site differences to
      confirm previous research, and to explore implications of differences across
      populations for future investigations. METHODS: We recruited schizophrenia
      samples in Australia (n = 609), India (n = 310) and Sarawak (n = 205) primarily
      for the purposes of genetic studies. We analyzed seven identified variables and
      their relationship to site using logistic regression, including: global
      delusions, bizarre delusions, thought broadcast/insertion/withdrawal delusions,
      global hallucinations, auditory hallucinations, disorganized behavior, and
      prodromal duration. RESULTS: We identified a distinct symptom profile in our
      Sarawak sample. Specifically, the Iban exhibit: low frequency of thought
      broadcast/insertion/withdrawal delusions, high frequency of auditory
      hallucinations and disorganized behavior, with a comparatively short prodrome
      when compared with Australian and Indian populations. DISCUSSION: Understanding
      between-site variation in symptom profile may complement future transethnic
      genetic studies, and provide important clues as to the nature of differing
      schizophrenia expression across ethnically distinct groups. A comprehensive
      approach to subtyping schizophrenia is warranted, utilizing comprehensively
      ascertained transethnic samples to inform both schizophrenia genetics and
      nosology.

PMID- 24038816
TI  - Postconcussional disorder and PTSD symptoms of military-related traumatic brain
      injury associated with compromised neurocircuitry.
AB  - Traumatic brain injury (TBI) is a common combat injury, often through explosive
      blast, and produces heterogeneous brain changes due to various mechanisms of
      injury. It is unclear whether the vulnerability of white matter differs between
      blast and impact injury, and the consequences of microstructural changes on
      neuropsychological function are poorly understood in military TBI patients.
      Diffusion tensor imaging (DTI) techniques were used to assess the neurocircuitry
      in 37 U.S. service members (29 mild, 7 moderate, 1 severe; 17 blast and 20
      nonblast), who sustained a TBI while deployed, compared to 14 nondeployed,
      military controls. High-dimensional deformable registration of MRI diffusion
      tensor data was followed by fiber tracking and tract-specific analysis along with
      region-of-interest analysis. DTI results were examined in relation to post
      concussion and post-traumatic stress disorder (PTSD) symptoms. The most prominent
      white matter microstructural injury for both blast and nonblast patients was in
      the frontal fibers within the fronto-striatal (corona radiata, internal capsule)
      and fronto-limbic circuits (fornix, cingulum), the fronto-parieto-occipital
      association fibers, in brainstem fibers, and in callosal fibers. Subcortical
      superior-inferiorly oriented tracts were more vulnerable to blast injury than
      nonblast injury, while direct impact force had more detrimental effects on
      anterior-posteriorly oriented tracts, which tended to cause heterogeneous left
      and right hemispheric asymmetries of white matter connectivity. The tractography
      using diffusion anisotropy deficits revealed the cortico-striatal-thalamic
      cerebellar-cortical (CSTCC) networks, where increased post-concussion and PTSD
      symptoms were associated with low fractional anisotropy in the major nodes of
      compromised CSTCC neurocircuitry, and the consequences on cognitive function were
      explored as well.

PMID- 24038817
TI  - Angiographic fate of side branch dissections in bifurcation lesions treated with
      a provisional single stenting strategy: a post-hoc analysis of the international
      multicenter randomized DEBIUT study.
AB  - BACKGROUND: The provisional single stenting strategy is currently the preferred
      treatment strategy in bifurcation lesions. However, in case of nonflow limiting
      side branch (SB) dissections, it is not clear whether outcomes may be inferior to
      coronaries without a SB dissection, whether it can be safe to leave a SB
      dissection untreated, and whether bail-out SB stenting provides benefits over
      conservative treatment. METHODS: Bifurcation lesions treated with a provisional
      single stenting in the randomized DEBIUT were screened according to the presence
      or absence of SB dissections. Additional treatment (with possible stent
      implantation) or conservative management was left to the discretion of the
      operator. RESULTS: Out of the 117 lesions included, 18 (15.4%) angiographic SB
      dissections were seen following intervention (type A = 3, B = 7, C = 6, D/E = 2),
      9 (50%) were treated with additional stenting, while 9 (50%) were left untreated.
      At 6-month follow up, all dissections that were left untreated were healed. The
      late-luminal loss was similar (P = 0.33) between patients without dissection
      (0.11 mm [-0.22 to 0.43 mm]) and with dissection (0.29 mm [-0.28 to 0.88 mm]).
      The late-luminal loss was nonsignificantly lower (P = 0.40) in the nonstented
      dissection group (-0.01 mm [-0.33 to 0.87 mm]), than in the stented dissection
      group (0.41 mm [-0.20 to 0.97 mm]), while binary restenosis was 1 (13%) and 2
      (25%), respectively. CONCLUSION: Coronary SB dissections have similar 6-month
      angiographic late-luminal loss as lesions without SB dissection, with complete
      angiographic healing of the dissections. Moreover, this study suggests that in
      case of a dissection, if operators consider it safe not to stent the dissection,
      this can lead to a satisfactory result at mid-term follow-up.

PMID- 24038818
TI  - [3+2] Fragmentation of an [RP(5)Cl](+) cage cation induced by an N-heterocyclic
      carbene.
AB  - The cage compound [DippP5 Cl][GaCl4 ] (Dipp=2,6-diisopropylphenyl) reacts with an
      NHC (N-heterocyclic carbene) by an unprecedented [3+2] fragmentation of the P5
      (+) core. This yields an imidazoliumyl-substituted P3 species featuring a
      triphosphaallyl anion motif and a neutral P2 compound. The mechanism of the
      fragmentation reaction was elucidated by means of experimental and quantum
      chemical methods. 

PMID- 24038820
TI  - Sub-lethal effects of the neurotoxic pyrethroid insecticide Fastac 50EC on the
      general motor and locomotor activities of the non-targeted beneficial carabid
      beetle Platynus assimilis (Coleoptera: Carabidae).
AB  - BACKGROUND: Sub-lethal effects of pesticides on behavioural endpoints are poorly
      studied in carabids (Coleoptera: Carabidae) though changes in behaviour caused by
      chemical stress may affect populations of these non-targeted beneficial insects.
      General motor activity and locomotion are inherent in many behavioural patterns,
      and changes in these activities that result from xenobiotic influence mirror an
      integrated response of the insect to pesticides. Influence of pyrethroid
      insecticides over a wide range of sub-lethal doses on the motor activities of
      carabids still remains unclear. RESULTS: Video tracking of Platynus assimilis
      showed that brief exposure to alpha-cypermethrin at sub-lethal concentrations
      ranged from 0.01 to 100 mg L(-1) caused initial short-term (< 2 h) locomotor
      hyperactivity followed by a long-term (>24 h) locomotor hypo-activity. In
      addition, significant short- and long-term concentration and time-dependent
      changes occurred in general motor activity patterns and rates. CONCLUSION:
      Conspicuous changes in motor activity of Platynus assimilis beetles treated at
      alpha-cypermethrin concentrations up to 75,000-fold lower than maximum field
      recommended concentration (MFRC) suggest that many, basic fitness-related
      behaviours might be severely injured as well. These changes may negatively affect
      carabid populations in agro-ecosystems. Long-term hypo-activity could directly
      contribute to decreased trap captures of carabids frequently observed after
      insecticide application in the field.

PMID- 24038821
TI  - Chemical signals turn on guest binding through structural reconfiguration of
      triangular helicates.
AB  - Be my guest: The function of a system based on self-assembled Zn(II) complexes
      can be controlled by external chemical stimuli. The complexes are based on a C3 
      symmetric ligand that forms a unique triangular triple helicate structure 1. Upon
      subcomponent substitution, 1 is able to transform into a triangular double
      helicate 2 which, unlike 1, can encapsulate guests. 

PMID- 24038819
TI  - Epigenetic studies in Alzheimer's disease: current findings, caveats, and
      considerations for future studies.
AB  - Alzheimer's disease (AD) is a sporadic, chronic neurodegenerative disease,
      usually occurring late in life. The last decade has witnessed tremendous advances
      in our understanding about the genetic basis of AD, but a large amount of the
      variance in disease risk remains to be explained. Epigenetic mechanisms, which
      developmentally regulate gene expression via modifications to DNA, histone
      proteins, and chromatin, have been hypothesized to play a role in other complex
      neurobiological diseases, and studies to identify genome-wide epigenetic changes
      in AD are currently under way. However, the simple brute-force approach that has
      been successfully employed in genome-wide association studies is unlikely to be
      successful in epigenome-wide association studies of neurodegeneration. A more
      academic approach to understanding the role of epigenetic variation in AD is
      required, with careful consideration of study design, methodological approaches,
      tissue-specificity, and causal inference. In this article, we review the
      empirical literature supporting a role for epigenetic processes in AD, and
      discuss important considerations and future directions for this new and emerging
      field of research.

PMID- 24038822
TI  - Long-term changes in hypoxia and soluble reactive phosphorus in the hypolimnion
      of a large temperate lake: consequences of a climate regime shift.
AB  - The (Lower) Lake of Zurich provides an ideal system for studying the long-term
      impact of environmental change on deep-water hypoxia because of its sensitivity
      to climatic forcing, its history of eutrophication and subsequent
      oligotrophication, and the quality and length of its data set. Based on 39 years
      (1972-2010) of measured profiles of temperature, oxygen concentration and
      phosphorus (P) concentration, the potentially confounding effects of
      oligotrophication and climatic forcing on the occurrence and extent of deep-water
      hypoxia in the lake were investigated. The time-series of Nurnberg's hypoxic
      factor (HF) for the lake can be divided into three distinct segments: (i) a
      segment of consistently low HF from 1972 to the late-1980s climate regime shift
      (CRS); (ii) a transitional segment between the late-1980s CRS and approximately
      2000 within which the HF was highly variable; and (iii) a segment of consistently
      high HF thereafter. The increase in hypoxia during the study period was not a
      consequence of a change in trophic status, as the lake underwent
      oligotrophication as a result of reduced external P loading during this time.
      Instead, wavelet analysis suggests that changes in the lake's mixing regime,
      initiated by the late-1980s CRS, ultimately led to a delayed but abrupt decrease
      in the deep-water oxygen concentration, resulting in a general expansion of the
      hypoxic zone in autumn. Even after detrending to remove long-term effects, the
      concentration of soluble reactive P in the bottom water of the lake was highly
      correlated with various measures of hypoxia, providing quantitative evidence
      supporting the probable effect of hypoxia on internal P loading. Such climate
      induced, ecosystem-scale changes, which may result in undesirable effects such as
      a decline in water quality and a reduction in coldwater fish habitats, provide
      further evidence for the vulnerability of large temperate lakes to predicted
      increases in global air temperature. 

PMID- 24038823
TI  - Silver-Russell syndrome due to paternal H19/IGF2 hypomethylation in a twin girl
      born after in vitro fertilization.
AB  - Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous
      syndrome characterized by severe intrauterine and postnatal growth retardation,
      facial dysmorphism and body asymmetry. One of the main molecular mechanisms
      leading to the syndrome involves methylation abnormalities of chromosome 11p15.
      In the last decades, an increase of imprinting disorders have been reported in
      children born from assisted reproductive technology (ART); however there is
      currently little evidence linking SRS and ART. Only few infants with SRS born
      using ART, supported by molecular analysis, have been described. We report on a
      twin-girl conceived using intracytoplasmic sperm injection (ICSI) diagnosed with
      SRS. Molecular studies revealed a hypomethylation of the paternal H19/IGF2
      Imprinting Control Region. Her twin sister had a normal prenatal and postnatal
      growth and a normal methylation pattern of the chromosome 11p15. This is the
      second reported case of a twin infant with SRS conceived using ART with
      hypomethylation of H19/IGF2; it provides additional evidence of a possible
      relationship between ART procedures and methylation defects observed in SRS.
      Given the clinical heterogeneity of SRS, and the increased risk of multiple and
      preterm births in the ART-conceived children, it is possible that a number of
      cases of SRS remains undiagnosed in this population. Future studies should
      investigate the possible link between ART and SRS, in order to better understand
      the causes of epimutations in ART pregnancies, and to help clinicians to
      adequately counsel parents who approach to ART and to assess the opportunity of a
      long-term follow-up of children conceived using ART.

PMID- 24038827
TI  - Unexpected role of anionic ligands in the ruthenium-catalyzed base-free selective
      hydrogenation of aldehydes.
AB  - Bigger and better: The replacement of anionic chloride ligands in Noyori-type
      [(diamine)(diphosphine)RuCl2 ] catalysts with bulky carboxylate ligands enabled
      the efficient selective hydrogenation of a variety of aldehydes under base-free
      conditions. Turnover numbers of up to 100 000 were reached in the presence of a
      bulky carboxylic acid co-catalyst. This type of catalytic system probably
      operates through an inner-sphere mechanism. 

PMID- 24038824
TI  - Water-soluble polymers coupled with glycopeptide antigens and T-cell epitopes as
      potential antitumor vaccines.
AB  - Highly decorated: Tumor-associated MUC1 glycopeptide and tetanus toxoid T-cell
      epitope P2 can be attached to water-soluble poly(N-(2
      hydroxypropyl)methacrylamide) carriers by orthogonal ligation techniques. Fully
      synthetic vaccine A with additional nanostructure-promoting domains induced
      antibodies that exhibit high affinity to tumor cells.

PMID- 24038828
TI  - Biosynthesis of the antimetabolite 6-thioguanine in Erwinia amylovora plays a key
      role in fire blight pathogenesis.
AB  - Sulfur for fire: The molecular basis for the biosynthesis of the antimetabolite 6
      thioguanine (6TG) was unveiled in Erwinia amylovora, the causative agent of fire
      blight. Bioinformatics, heterologous pathway reconstitution in E. coli, and
      mutational analyses indicate that the protein YcfA mediates guanine thionation in
      analogy to 2-thiouridylase. Assays in planta and in cell cultures reveal for the
      first time a crucial role of 6TG in fire blight pathogenesis.

PMID- 24038830
TI  - Nanoplasmonic imaging of latent fingerprints and identification of cocaine.
AB  - Search for traces: Aptamer-bound Au nanoparticles (Au NPs) were used to provide
      high-resolution dark-field microscopy images of latent fingerprints (LFPs) with
      level 2 and level 3 details. Furthermore, the cocaine-induced aggregation of Au
      NPs results in a true green-to-red color change of the scattered light, providing
      a quasi-quantative method to identify cocaine loadings in LFPs. 

PMID- 24038829
TI  - Pregnancy after cancer: results from a prospective cohort study of cancer
      survivors.
AB  - BACKGROUND: Future fertility is an important concern for many cancer survivors.
      Cancer therapies have been shown to adversely impact reproductive function.
      However, it is difficult to predict the extent to which reproductive dysfunction
      will occur. The purpose of this study was to compare measures of ovarian reserve
      (MOR) and pregnancy rates in young female cancer survivors and similar-aged
      controls. PROCEDURES: A prospective cohort study was conducted in a university
      hospital setting. Participants were followed annually for a mean 25 months to
      assess reproductive history, the incidence of pregnancy, and MOR (serum follicle
      stimulating hormone, luteinizing hormone, estradiol, inhibin B, anti-mullerian
      hormone (AMH), antral follicle counts and mean ovarian volume). RESULTS: Eighty
      four female survivors (average age 26, and 14 years post-treatment) and 98
      similar-aged controls that were sexually active with men were included. At
      baseline, 27/84 survivors and 42/98 controls reported a prior pregnancy. Adjusted
      models showed that anti-mullerian hormone (AMH) and antral follicle count (AFC)
      were impaired in survivors with a prior pregnancy compared to controls with a
      prior pregnancy (P < 0.01, P = 0.03). During follow-up in 56 survivors and 74
      controls, 19 pregnancies occurred in survivors and 18 in controls. Comparison of
      MOR between survivors who became pregnant and controls who became pregnant
      revealed that AMH and AFC were impaired in survivors (P < 0.05). Compared to
      survivors who did not become pregnant, survivors who did were older (P < 0.01)
      and more likely to be cohabitating (P < 0.01), but had similar MOR and exposure
      to alkylators (P = 0.34). CONCLUSIONS: Survivors achieved pregnancy at a rate
      similar to controls despite impaired MOR.

PMID- 24038831
TI  - Acute and chronic stress exposure predicts 1-year recurrence in adult outpatients
      with residual depression symptoms following response to treatment.
AB  - BACKGROUND: One of the strongest predictors of depression recurrence in those who
      respond to treatment is the presence of residual depressive symptoms. Our goal
      was to examine stressful life event exposure as a mechanism of recurrence in
      previously depressed patients with residual depression symptoms. That is, we
      predicted that higher levels of residual symptoms will significantly predict
      exposure to acute life events that will then heighten prospective recurrence
      risk. METHODS: Participants included 68 adult outpatients with major depression
      (42 women; age 18-60) who completed a 12-month naturalistic follow-up after
      achieving remission in a 20-week randomized, open label trial of interpersonal
      psychotherapy, cognitive-behavioral therapy, or antidepressant medication.
      Depression recurrence was defined as the reemergence of an episode of major
      depression as determined by structured interview. Acute life events and chronic
      stressors were assessed at the end of follow-up using a contextual interview.
      RESULTS: Posttreatment depression scores significantly prospectively predicted an
      increased risk for recurrence, and acute life events in the follow-up period. Cox
      regression survival analyses modeling life events as time-dependent covariates
      showed that life event exposure mediated the relation of residual symptoms to
      recurrence even controlling for chronic stress. CONCLUSIONS: Our findings
      implicate residual symptoms in heightening depression recurrence risk through
      exposure to stressful life events. Depression recurrence adds significantly to
      the burden of the disorder. Therefore, rigorous follow-up of patients targeting
      the stressful context has the potential to prevent a lifelong pattern of illness.

PMID- 24038832
TI  - Rescue of functional CFTR channels in cystic fibrosis: a dramatic multivalent
      effect using iminosugar cluster-based correctors.
AB  - Cystic fibrosis is caused by a mutation in the gene for the cystic fibrosis
      transmembrane conductance regulator (CFTR) protein. N-butyl 1-deoxynojirimycin (N
      Bu DNJ), a clinical candidate for the treatment of cystic fibrosis, is able to
      act as a CFTR corrector by overcoming the processing defect of the mutant
      protein. To explore the potential of multivalency on CFTR correction activity, a
      library of twelve DNJ click clusters with valencies ranging from 3 to 14 were
      synthesized. Significantly, the trivalent analogues were found to be up to 225
      fold more potent than N-Bu DNJ and up to 1000-fold more potent than the
      corresponding monovalent models. These results provide the first description of a
      multivalent effect for correcting protein folding defects in cells and should
      have application for the treatment of a number of protein folding disorders.
      Preliminary mechanistic studies indicated that CFTR correction activity
      enhancement was not due to a multivalent effect in ER-glucosidase inhibition or
      to a different mode of action of the multivalent iminosugars. 

PMID- 24038833
TI  - Estimating hospital costs of catheter-associated urinary tract infection.
AB  - Healthcare-associated infections are common, costly, and potentially deadly.
      However, effective prevention strategies are underutilized, particularly for
      catheter-associated urinary tract infection (CAUTI), one of the most common
      healthcare-associated infections. Further, since 2008, the Centers for Medicare
      and Medicaid Services no longer reimburses hospitals for the additional costs of
      caring for patients who develop CAUTI during hospitalization. Given the resulting
      payment pressures on hospitals stemming from this decision, it is important to
      factor in cost implications when attempting to encourage decision makers to
      support infection prevention measures. To this end, we present a simple tool
      (with easy-to-use online implementation) that hospitals can use to estimate
      hospital costs due to CAUTI, both before and after an intervention, to reduce
      inappropriate urinary catheterization. Using previously published cost and risk
      estimates, we show that an intervention yielding clinically feasible reductions
      in catheter use can lead to an estimated 50% reduction in CAUTI-related costs.
      Our tool is meant to complement the Society of Hospital Medicine's Choosing
      Wisely campaign, which highlights avoiding placement or continued use of
      nonindicated urinary catheters as a key area for improving decision making and
      quality of care while decreasing costs.

PMID- 24038834
TI  - Observational study to evaluate the clinical benefit of lamotrigine add-on
      therapy in bipolar patients in a naturalistic treatment setting.
AB  - INTRODUCTION: The objective of the current study was to assess, in a naturalistic
      treatment setting, the clinical benefits of lamotrigine add-on therapy for
      patients with bipolar disorder. METHODS: This was an open-label, prospective,
      naturalistic, 12-week, observational study that included 98 bipolar patients
      treated with lamotrigine add-on therapy, in addition to mood stabilizers or
      atypical antipsychotics for 1-4 weeks. The clinical benefits of lamotrigine
      augmentation were evaluated using the Clinical Global Impression-Clinical Benefit
      (CGI-CB) Scale, and the Clinical Global Impression of Bipolar Disorder-Severity
      scale was used to evaluate the severity of the patients' conditions. RESULTS:
      According to paired t-test analyses, the mean CGI-CB score significantly
      decreased from 7.2 +/- 2.7 at baseline to 3.8 +/- 2.5 at Week 12. Likewise, the
      mean score for Clinical Global Impression of Bipolar Disorder-Severity scale
      significantly decreased from 4.7 +/- 0.9 at baseline to 3.1 +/- 1.2 at Week 12.
      Analysis of covariance showed that the extent to which CGI-CB scores changed from
      baseline to Week 12 did not significantly differ between patients with bipolar I
      and II disorder. However, the change in CGI-CB scores between Weeks 4 and 12 was
      significantly smaller in bipolar II patients than bipolar I patients. A total of
      21 (21.4%) patients dropped out during the course of the study, and 30 patients
      (30.6%) reported 82 adverse events. DISCUSSION: The results of this study
      demonstrated that the use of lamotrigine in patients with bipolar disorder,
      especially those whom conventional mood stabilizers or antipsychotics are
      insufficiently effective or intolerable, can be beneficial regardless of the type
      of bipolar disorder.

PMID- 24038836
TI  - Risk factors for thromboembolism and pulmonary artery hypertension following
      splenectomy in children with hereditary spherocytosis.
AB  - BACKGROUND: The aim was to study risk-factors for vascular thrombosis and
      incidence of pulmonary artery hypertension (PAH) in splenectomized children with
      hereditary spherocytosis (HS) at a single center. PROCEDURE: Pre- and post
      splenectomy hemoglobin and platelet counts were recorded. Post-splenectomy lipid
      profile, fibrinogen, D-dimer, CRP and anti-coagulant-protein levels were compared
      to established controls. Echo-Doppler was performed for PAH. RESULTS: Twenty-six
      children with HS had undergone splenectomy; the mean age at surgery was 7.9 +/-
      3.7 years. Nineteen of the 26 were prospectively investigated at a median
      duration of 4.5 years (range: 4 months to 19 years) following splenectomy.
      Thrombocytosis was observed in 19 (73%), whereas no patient had erythrocytosis at
      the last follow-up visit. Total cholesterol, LDL-C, HDL-C, and triglyceride
      levels were not deranged (P >= 0.3). Mean CRP levels (males: 2.8 +/- 0.5;
      females: 2.1 +/- 0.5 mg/L) were significantly higher than described for normal
      children (P < 0.001). Six (23%) patients had a positive D-dimer assay. Protein S,
      anti-thrombin-III and fibrinogen were in range. A single patient had a borderline
      low protein C activity. Lupus anticoagulant and anti-cardiolipin antibody assays
      were negative. The mean tricuspid regurgitant jet velocity (TRJV) was 1.8 +/-
      0.55 meter per second (range: 0-2.4). None had a TRJV >=2.5 meter per second to
      suggest PAH. CONCLUSIONS: There was no evidence of PAH, dyslipidemia, elevation
      of fibrinogen or a reduction in anti-coagulant proteins, at a median follow-up
      duration of 4.5 years following splenectomy in children with HS. However,
      elevated CRP level (42%), persistent thrombocytosis (73%) and elevated D-dimer
      levels (23%) were observed. These have been recognized as risk factors for
      cerebrovascular and coronary heart disease.

PMID- 24038838
TI  - Postdilatation for treatment of perivalvular aortic regurgitation after
      transcatheter aortic valve implantation.
AB  - OBJECTIVES: The study is made to describe the efficacy and safety of balloon
      postdilatation (BPD) for the treatment of residual aortic regurgitation (RAoR)
      after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: A
      single-center observational study is made with 157 consecutive patients accepted
      to TAVI. The patients were divided into two groups (no BPD-period and BPD
      period). Before BPD, RAoR >= 2 was seen in 25% of the patients in group 1 and in
      29% of the patients in group 2 (P >= 0.593). BPD was carried out in 95% (n = 21)
      of the patients in group 2 with RAoR >= 2. Regurgitation improved one grade in
      68% of the cases (n = 15), 2 grades in 14% (n = 3), and remained without change
      in 18% (n = 4). RAoR < 2 was achieved in 91% (n = 73) of the patients in group 2
      versus 75% (n = 58) in group 1 (RR = 0.35, 95% CI 0.16-0.80, P = 0.013). We
      recorded no aortic ring ruptures, damage to the device or displacements. Slight
      central regurgitation not present before BPD was registered in one case.
      CONCLUSIONS: BPD offers a very good safety profile and reduces RAoR in a large
      percentage of cases. BPD should be considered for the treatment of moderate to
      severe RAoR following TAVI.

PMID- 24038837
TI  - Differential developmental trajectories of magnetic susceptibility in human brain
      gray and white matter over the lifespan.
AB  - As indicated by several recent studies, magnetic susceptibility of the brain is
      influenced mainly by myelin in the white matter and by iron deposits in the deep
      nuclei. Myelination and iron deposition in the brain evolve both spatially and
      temporally. This evolution reflects an important characteristic of normal brain
      development and ageing. In this study, we assessed the changes of regional
      susceptibility in the human brain in vivo by examining the developmental and
      ageing process from 1 to 83 years of age. The evolution of magnetic
      susceptibility over this lifespan was found to display differential trajectories
      between the gray and the white matter. In both cortical and subcortical white
      matter, an initial decrease followed by a subsequent increase in magnetic
      susceptibility was observed, which could be fitted by a Poisson curve. In the
      gray matter, including the cortical gray matter and the iron-rich deep nuclei,
      magnetic susceptibility displayed a monotonic increase that can be described by
      an exponential growth. The rate of change varied according to functional and
      anatomical regions of the brain. For the brain nuclei, the age-related changes of
      susceptibility were in good agreement with the findings from R2* measurement. Our
      results suggest that magnetic susceptibility may provide valuable information
      regarding the spatial and temporal patterns of brain myelination and iron
      deposition during brain maturation and ageing.

PMID- 24038839
TI  - Sensitive detection of KRAS mutations using enhanced-ice-COLD-PCR mutation
      enrichment and direct sequence identification.
AB  - A number of methods allowing the detection of low levels of KRAS mutations have
      been developed in the last years. However, although these methods have become
      increasingly sensitive, they can rarely identify the mutated base directly
      without prior knowledge on the mutated base and are often incompatible with a
      sequencing-based read-out desirable in clinical practice. Here, we present a
      modified version of the ice-COLD-PCR assay called Enhanced-ice-COLD-PCR (E-ice
      COLD-PCR) for KRAS mutation detection and identification, which allows the
      enrichment of the six most frequent KRAS mutations. The method is based on a
      nonextendable chemically modified blocker sequence, complementary to the wild
      type (WT) sequence leading to the enrichment of mutated sequences. This assay
      permits the reliable detection of down to 0.1% mutated sequences in a WT
      background. A single genotyping assay of the amplification product by
      pyrosequencing directly following the E-ice-COLD-PCR is performed to identify the
      mutated base. This developed two-step method is rapid and cost-effective, and
      requires only a small amount of starting material permitting the sensitive
      detection and sequence identification of KRAS mutations within 3 hr. This method
      is applied in the current study to clinical colorectal cancer samples and enables
      detection of mutations in samples, which appear as WT using standard detection
      technologies. 

PMID- 24038840
TI  - Microscopy of molecular interactions.

PMID- 24038845
TI  - Facile access to tuneable Schwartz's reagents: oxidative addition products from
      the reaction of amide N-H bonds with reduced zirconocene complexes.
AB  - On the tracks of Schwartz's reagent: Two zirconocene hydrido amidate complexes
      are synthesized by formal oxidative addition of amide N?H bonds to reduced
      zirconocene fragments. Insertion reactions with alkenes show a different behavior
      than Schwartz's reagent by forming branched insertion products. The insertion
      product and the hydrido complex are characterized by X-ray analysis. 

PMID- 24038844
TI  - Geographic susceptibility of Chilo suppressalis Walker (Lepidoptera: Crambidae),
      to chlorantraniliprole in China.
AB  - BACKGROUND: Chilo suppressalis Walker, the rice striped stem borer (RSSB) is one
      of the most serious lepidopteron insect pests of rice in Asia. The registration
      of chlorantraniliprole added an option for the chemical control of RSSBs.
      RESULTS: In this study, the geographic variability of susceptibility of field
      collected RSSBs to chlorantraniliprole was assessed to establish a baseline for
      future comparisons of field population responses to the increased use of
      chlorantraniliprole products. Thirty-one RSSB colonies were established from 22
      geographic areas in seven provinces of China, and were evaluated for
      chlorantraniliprole susceptibility. The range of mean lethal concentration (LC50
      ) values in response to this chemical was between 0.821 and 17.720 mg (AI)/L
      across the populations. Susceptibility was significantly different (21.7-fold for
      LC50 and 55.6-fold for LC90 ) across the various geographic populations. No
      significant correlations were detected between the LC50 values of
      chlorantraniliprole and four conventional insecticides (monosultap, triazophos,
      chlorpyrifos and abamectin). CONCLUSION: These results revealed great
      geographical variations in chlorantraniliprole susceptibilities among different
      geographic populations of RSSBs, which might indicate the potential for RSSBs to
      develop resistance to chlorantraniliprole. The effective execution of insecticide
      resistance monitoring programs and management strategies is urgently needed in
      China to sustain RSSB susceptibility to chlorantraniliprole.

PMID- 24038846
TI  - Controlling photons in a box and exploring the quantum to classical boundary
      (Nobel Lecture).
AB  - Microwave photons trapped in a superconducting cavity constitute an ideal system
      to realize some of the thought experiments imagined by the founding fathers of
      quantum physics. The interaction of these trapped photons with Rydberg atoms
      crossing the cavity illustrates fundamental aspects of measurement theory. The
      experiments performed with this "photon box" at Ecole Normale Superieure (ENS)
      belong to the domain of quantum optics called "Cavity Quantum Electrodynamics".
      We have realized the non-destructive counting of photons, the recording of field
      quantum jumps, the preparation and reconstruction of "Schrodinger cat" states of
      radiation and the study of their decoherence, which provides a striking
      illustration of the transition from the quantum to the classical world. These
      experiments have also led to the demonstration of basic steps in quantum
      information processing, including the deterministic entanglement of atoms and the
      realization of quantum gates using atoms and photons as quantum bits. This
      lecture starts by an introduction stressing the connection between the ENS photon
      box and the ion trap experiments of David Wineland, whose accompanying lecture
      recalls his own contribution to the field of single particle control. I give then
      a personal account of the early days of Cavity Quantum Electrodynamics before
      describing the main experiments performed at ENS during the last twenty years and
      concluding by a discussion comparing our work to other researches dealing with
      the control of single quantum particles. 

PMID- 24038847
TI  - Na(+) /H(+) exchanger 1 (NHE1) function is necessary for maintaining mammary
      tissue architecture.
AB  - BACKGROUND: The mammary gland is an ideal model to study the link between form
      and function in normal tissue. Perhaps as interesting as the cues necessary to
      generate this structure are the signals required to maintain its branched
      architecture over the lifetime of the organism, since likely these pathways are
      de-regulated in malignancies. Previously, we have shown that the Na(+) /H(+)
      exchanger 1 (NHE1), a critical regulator of intracellular pH, was necessary for
      mammary branching morphogenesis. Here we provide strong evidence that NHE1
      function is also necessary for maintaining mammary branched architecture.
      RESULTS: Inhibition of NHE1 with 5-N-Methy-N-isobutyl amiloride (MIA) on branched
      structures resulted in a rapid (within 24 hr) and reversible loss of branched
      architecture that was not accompanied by any overt changes in cell proliferation
      or cell death. NHE1 inhibition led to a significant acidification of
      intracellular pH in the branched end buds that preceded a number of events,
      including altered tissue polarity of myoepithelial cells, loss of NHE1 basal
      polarity, F-actin rearrangements, and decreased E-cadherin expression.
      CONCLUSIONS: Our results implicate NHE1 function and intracellular pH homeostasis
      as key factors that maintain mammary tissue architecture, thus, indirectly
      allowing for mammary function as a milk-providing (form) and -producing
      (function) gland.

PMID- 24038849
TI  - [BH(3)C(NO(2))(3)](-) : the first room-temperature stable (trinitromethyl)borate.
AB  - The marriage of fire and water: The strongly oxidizing trinitromethyl and
      strongly reducing BH3 groups were successfully combined for the first time in the
      novel [BH3 C(NO2 )3 ](-) ion. The stability at room temperature of the new
      (trinitromethyl)borate is in sharp contrast to the behavior of [BCl3 C(NO2 )3 ](
      ) , which already decomposes at -20  degrees C. 

PMID- 24038850
TI  - Unambiguous characterization of a photoreactive ligand-loss intermediate.

PMID- 24038848
TI  - Bilaterally cleft lip and bilateral thumb polydactyly with triphalangeal
      component in a patient with two de novo deletions of HSA 4q32 and 4q34 involving
      PDGFC, GRIA2, and FBXO8 genes.
AB  - We report on a newborn boy with a bilateral cleft of the primary palate,
      duplicated triphalangeal thumbs, and a patent foramen ovale. During childhood he
      had moderate developmental delay. Brain MRI at 4 years was normal. The
      concurrence of non-syndromic clefts of the lip/palate (CL/P) and duplicated
      thumbs with triphalangeal component has, to our knowledge, not been reported so
      far. In our case, array-CGH analysis documented two de novo deletions (~1.2 Mb
      and ~400 Kb) of the long arm of chromosome 4, containing four genes: platelet
      derived growth factor C (PDGFC), glycine receptor beta subunit (GLRB), glutamate
      receptor ionotropic AMPA2 (GRIA2), and F-box protein 8 gene (FBXO8). PDGFC codes
      for a mesenchymal cell growth factor already known to be associated with clefts
      of the lip. Pdgfc(-/-) mice have skeletal anomalies, and facial schisis
      resembling human cleft/lip palate. GRIA2 codes for a ligand-activated cation
      channel that mediates the fast component of postsynaptic excitatory currents in
      neurons, and may be linked to cognitive dysfunction. FBXO8, a gene of unknown
      function, is a member of the F-box gene family, among which FBXW4, within the
      minimal duplicated region associated with human split-hand/foot malformation type
      3 (SHFM type 3). The presence of overlapping deletions in patients who do not
      share the same phenotype of our case suggests incomplete penetrance, and a
      possible effect of modifier genetic factors.

PMID- 24038851
TI  - Mechanochemical properties of individual human telomeric RNA (TERRA) G
      quadruplexes.
AB  - Potential functions: By following the unfolding and refolding of individual human
      RNA telomeric (TERRA) G-quadruplexes (GQs) in laser tweezers, the mechanical
      stability and transition kinetics of RNA GQs are obtained. Comparison between
      TERRA and DNA GQs suggests their different regulatory capacities for processes
      associated with human telomeres. 

PMID- 24038852
TI  - Effects of oral anorexiant sibutramine on the expression of cytochromes P450s in
      human hepatocytes and cancer cell lines.
AB  - Sibutramine is a serotonin-norepinephrine reuptake inhibitor that was used for
      weight-loss management in obese patients. Even though it was officially withdrawn
      from the market in 2010, it is still present in some tainted weight-loss pills
      (as reported by US Food and Drug Administration). Thus, it is still reasonable to
      study the effects of this compound. The aim of this work was to investigate the
      potential of sibutramine to induce CYP1A1/CY3A4 in human cancer cell lines and
      CYP1A1/2, CYP2A6, CYP2B6, and CYP3A4 in human hepatocytes, a competent model of
      metabolically active cells. The levels of mRNA and protein of
      CYP1A1/1A2/3A4/2A6/2B6 were compared with the typical inducers, 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and rifampicin (RIF) for CYP1A1/2 and for
      other CYPs, respectively. The mRNA and protein levels of all genes in either
      cancer cell lines or human hepatocytes were induced when treated with typical
      inducers but not with sibutramine.

PMID- 24038853
TI  - Critical growth temperature of aqueous CdTe quantum dots is non-negligible for
      their application as nanothermometers.

PMID- 24038855
TI  - Phenology predicts the native and invasive range limits of common ragweed.
AB  - Accurate models for species' distributions are needed to forecast the progress
      and impacts of alien invasive species and assess potential range-shifting driven
      by global change. Although this has traditionally been achieved through data
      driven correlative modelling, robustly extrapolating these models into novel
      climatic conditions is challenging. Recently, a small number of process-based or
      mechanistic distribution models have been developed to complement the correlative
      approaches. However, tests of these models are lacking, and there are very few
      process-based models for invasive species. We develop a method for estimating the
      range of a globally invasive species, common ragweed (Ambrosia artemisiifolia
      L.), from a temperature- and photoperiod-driven phenology model. The model
      predicts the region in which ragweed can reach reproductive maturity before frost
      kills the adult plants in autumn. This aligns well with the poleward and high
      elevation range limits in its native North America and in invaded Europe, clearly
      showing that phenological constraints determine the cold range margins of the
      species. Importantly, this is a 'forward' prediction made entirely independently
      of the distribution data. Therefore, it allows a confident and biologically
      informed forecasting of further invasion and range shifting driven by climate
      change. For ragweed, such forecasts are extremely important as the species is a
      serious crop weed and its airborne pollen is a major cause of allergy and asthma
      in humans. Our results show that phenology can be a key determinant of species'
      range margins, so integrating phenology into species distribution models offers
      great potential for the mechanistic modelling of range dynamics. 

PMID- 24038854
TI  - Cascade palladium catalysis: a predictable and selectable regiocontrolled
      synthesis of N-arylbenzimidazoles.
AB  - By choice: The palladium-catalyzed cascade reaction of 2-chloroaryl sulfonates
      with arylamine and amide nucleophiles provides direct access to N
      arylbenzimidazoles. This strategy selectively produces the heterocycles based on
      chemoselective oxidative addition. 2-Chloroaryl triflates (Tf) produce one
      regioisomer and the corresponding 2-chloroaryl mesylates (Ms) deliver the other
      in a selectable manner. 

PMID- 24038856
TI  - Newborn screening program for hemoglobinopathies in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Newborn screening for hemoglobinopathy in Brazil has been
      decentralized until 2001 when the Health Ministry of Brazil established the
      National Newborn Hemoglobinopathy Screening Program. The State of Rio de Janeiro
      started a program in collaboration with the State Health Department and the
      Institute of Hematology in Rio (HEMORIO). The goal of this study was to evaluate
      the effectiveness of the first 10 years of the Newborn Hemoglobinopathy Screening
      Program in identifying and managing infants with Sickle cell disease (SCD) in the
      State of Rio de Janeiro. PROCEDURE: Blood samples from 1,217,833 neonates were
      analyzed by High Performance Liquid Chromatography. Infants with SCD were
      enrolled in comprehensive treatment programs. RESULTS: Data showed that 4.87% of
      the newborns were heterozygous for a hemoglobin variant, 0.08% were homozygous or
      doubly heterozygous for abnormal hemoglobins and 95.02% had normal hemoglobin.
      All the 912 newborns with SCD were referred for treatment at HEMORIO, 34 (3.7%)
      of these died due to acute chest syndrome, sepsis or splenic sequestration. Four
      more children died of unknown causes. The implementation of the Rio de Janeiro
      Newborn Screening Program gradually increased the area of the State covered by
      the program. CONCLUSION: Data collected during the 10 years of the program showed
      reduction in mortality of patients with SCD in comparison to available historical
      statistical data before the implementation of the national screening program.
      This 10-year study showed that early diagnosis and treatment of newborns was
      associated with improved survival and quality of life of Brazilian children with
      SCD.

PMID- 24038857
TI  - Correlates of readmission risk and readmission days in a large psychiatric
      hospital in Guangzhou, China.
AB  - INTRODUCTION: For many patients with psychiatric disorders, the course of illness
      is characterized by frequent relapses, resulting to re-hospitalization and high
      costs. While the correlates of readmission have been extensively studied in
      developed countries, few studies have examined readmission in low- and middle
      income countries where bed supply is limited. METHODS: Using administrative data
      from the Guangzhou Psychiatric Hospital (GPH), we used Cox regression models to
      evaluate the relationship among age, gender, index length of stay (LOS), and the
      number of previous admissions to post-discharge readmission risk. Linear
      regression is used to evaluate predictors of total hospital days during the year
      after the index discharge. RESULTS: Between April 1, 2010 and March 31, 2011,
      2,525 patients were discharged with International Classification of Diseases,
      10th Revision psychiatric diagnoses from GPH, with an average LOS of 64.2 (SD =
      69.0), and 317 (12.4%) were readmitted in the following year. Survival analysis
      showed older age (P < 0.05), and the number of previous hospitalizations (P <
      0.01) were significant predictors of the risk of readmission but not diagnosis or
      LOS. The number of previous admissions was the only predictor of total bed days
      of psychiatric care at GPH in the year following the initial discharge.
      DISCUSSION: Shortened LOS was not associated with increased readmission risk or
      post-discharge hospital days. Rather, the number of past hospitalizations was the
      major predictor of both readmission risk and post-discharge hospital days of
      psychiatric care, and such patients deserve special attention. Lowering LOS may
      be justified, allowing funds to be redeployed to outpatient or community-based
      care.

PMID- 24038858
TI  - Should diabetic ketosis without acidosis be included in ketosis-prone type 2
      diabetes mellitus?
AB  - BACKGROUND: The incidence of ketosis-prone type 2 diabetes is very low except for
      people of sub-Saharan African origin and African Americans. However, there also
      are some type 2 diabetes patients with diabetic ketosis without acidosis (DKWA).
      We question whether DKWA should be included as a subtype of ketosis-prone type 2
      diabetes mellitus and compared the clinical characteristics of DKWA and diabetic
      ketoacidosis (DKA) patients. METHODS: The study population consisted of 594
      consecutive unrelated Chinese inpatients with newly diagnosed type 2 diabetes.
      Demographic and clinical characteristics (age, gender, family history of
      diabetes, body mass index, blood pressure and plasma lipid parameters) were
      recorded. The patients were divided into ketosis-resistant diabetes (KRD), DKWA
      and DKA groups on the basis of urinary ketones, blood pH and bicarbonate levels.
      The blood glucose and c-peptide levels of the patients were also evaluated.
      RESULTS: The prevalence of KRD, DKWA and DKA were 78.33%, 19.72% and 1.95%,
      respectively, in the study population. The clinical characteristics of patients
      with DKWA group patients were similar to those with DKA, except that DKA patients
      had higher blood glucose and deteriorated beta cell function. CONCLUSIONS:
      Diabetic ketosis without acidosis and DKA patients share similar clinical
      characteristics; DKWA should be considered ketosis-prone type 2 diabetes.
      Therefore, the prevalence of ketosis-prone type 2 diabetes might be
      underestimated.

PMID- 24038859
TI  - The study of epigenetic mechanisms based on the analysis of histone modification
      patterns by flow cytometry.
AB  - Epigenetic regulation of genes involved in cell growth, survival, or
      differentiation through histone modifications is an important determinant of
      cancer development and outcome. The basic science of epigenetics uses analytical
      tools that, although powerful, are not well suited to the analysis of
      heterogeneous cell populations found in human cancers, or for monitoring the
      effects of drugs designed to modulate epigenetic mechanisms in patients. To
      address this, we selected three clinically relevant histone marks (H3K27me3,
      H3K9ac, and H3K9me2), modulated their expression levels by in vitro treatments to
      generate high and low expressing control cells, and tested the relative
      sensitivity of candidate antibodies to detect the differences in expression
      levels by flow cytoametry using a range of sample preparation techniques. We
      identified monoclonal antibodies to all three histone marks that were suitable
      for flow cytoametry. Staining intensities were reduced with increasing
      formaldehyde concentration, and were not affected by ionic strength or by alcohol
      treatment. A protocol suitable for clinical samples was then developed, to allow
      combined labeling of histone marks and surface antigens while preserving light
      scatter signals. This was applied to normal donor blood, and to samples obtained
      from 25 patients with leukemia (predominantly acute myeloid leukemia).
      Significant cellular heterogeneity in H3K9ac and H3K27me3 staining was seen in
      normal peripheral blood, but the patterns were very similar between individual
      donors. In contrast, H3K27me3 in particular showed considerable inter-patient
      heterogeneity in the leukemia cell populations. Although further refinements are
      likely needed to fully optimize sample staining protocols, "flow epigenetics"
      appears to be technically feasible, and to have potential both in basic research,
      and in clinical application.

PMID- 24038860
TI  - Dear Doctor: a tool to facilitate patient-centered communication.
AB  - BACKGROUND: Patient-centered care has been identified as 1 of the 6 aims for the
      21st century healthcare system. The notepad is a simple tool for reminders and
      personal interactions. We introduced Dear Doctor (DD) notes, a bedside notepad
      designed to prompt patient questions and improve patient satisfaction. OBJECTIVE:
      To provide DD notes as a bedside tool to facilitate patient communication and
      improve patient encounters with physicians in the hospital. DESIGN: This is a
      single-center, cross-sectional survey. METHODS: Over a 3-month period (July 2009
      September 2009), all hospitalized patients in the intervention group (1 general
      medicine and 1 cardiology unit) at a large academic medical center received a DD
      notepad, a pen, and instructions on its use. We surveyed patients who received
      the DD notes on the intervention group (n = 440) and compared their responses to
      those from a matched control group (1 general medicine and 1 cardiology unit, n =
      224). RESULTS: Of the 440 patients surveyed in the intervention group, 78% (n =
      343) received the notepads in their rooms and 47% (n = 207) used them. Of the 343
      patients who received the DD notepads, 65% (n = 223) reported that they took
      notes related to their hospital stay compared to only 22% of 224 patients (n =
      50) in the control group (P < 0.001). The 207 patients using the DD notes had
      their questions more often answered by their physicians as measured on a 5-point
      Likert scale, compared to the control group (4.63 vs 4.45; P < 0.001). However,
      overall rating of communication did not differ between intervention and control
      groups in an intention-to-treat analysis (4.55 vs 4.55, P = 0.89). All patients
      who used the DD notepads responded on the survey that communication with their
      physicians was enhanced to at least some degree. CONCLUSIONS: Utilizing a bedside
      notepad improved patients' satisfaction with physician communication. A simple,
      low-cost, patient-centered tool such as the DD notes may enhance a patient's
      overall experience with their providers and the hospital.

PMID- 24038861
TI  - Echocardiographic predictors of cardiac erosion after Amplatzer septal occluder
      placement.
AB  - The risk of erosion after Amplatzer septal occluder (ASO) device placement in
      atrial septal defects is well described. Aortic rim deficiency and use of over
      sized device increase the risk of erosion. This study attempts to describe device
      characteristics, anatomical features and echocardiographic predictors that
      increase the risk of erosion. METHODS: From 2005 through 2012, 12 new cases, with
      nine confirmed and three suspected device erosions where pre-procedural, intra
      procedural, and/or post-procedural echocardiograms were available and, were
      reviewed. Following parameters were evaluated: ASD location (high or low), rims
      deficiency and consistency, septal mal-alignment, dynamic nature of the defect;
      device edge relationship toward the transverse sinus (TS), atrial free wall
      tenting and the size of the defect compared with the size of the device used for
      closure. RESULTS: We found poor posterior rim consistency, aortic rim absence (in
      multiple views) and absent aortic rim at O degree in 100% of the patients. Septal
      mal-alignment and dynamic ASD was present in nearly 50% of the cases. The device
      was over-sized in three patients only. A 26-mm device was the most common device
      that resulted in erosion. In cases, where patient had experienced bloody
      pericardial effusion and the device was in place, device tenting in the TS was
      observed. Surgical explantation of the device confirmed presence of erosion in
      all cases. CONCLUSION: Aortic rim absence in multiple views, poor posterior rim
      consistency, septal mal-alignment, and dynamic ASD appear to be factors where
      erosion risk increases significantly. A thorough assessment of the device edge by
      echocardiography in short-axis may show device tenting of the atrial free wall
      into the TS. This finding should be a strong indictor to recommend surgical
      removal of device after occurrence of pericardial effusion.

PMID- 24038862
TI  - Tumour supressor secreted frizzled related protein 1 regulates p53-mediated
      apoptosis.
AB  - The most frequently occurring cancer in women, and the second leading cause of
      cancer death among women, is breast cancer. Cancer results from cellular
      mutations that enhance proliferation and decrease programmed cell death
      (apoptosis). Secreted frizzled-related proteins (SFRPs) are a family of proteins
      known for their ability to negatively modulate the Wnt signalling cascade. SFRP1
      expression is lost in a multitude of cancers, including breast cancer, and SFRP1
      down regulation reduces apoptosis in vitro but the mechanisms remain unclear, as
      also the effect of Sfrp1 deficiency on apoptosis on mammary epithelial cells in
      vivo. Our data show that mammary glands from Sfrp1(-/-) mice express
      significantly less Bcl2l11 (Bim) and Bax mRNA in response to DNA damage. The
      effect of Sfrp1 loss in reducing gamma-irradiation induced apoptosis was examined
      by TUNEL staining and cleaved-caspase-3 immunostaining. The findings show that
      Sfrp1(-/-) mice have less DNA fragmentation, whilst caspase-3 expression is
      decreased, and that p53 expression is generally diminished. Recombinant SFRP1
      could replace endogenous expression and elevate the levels of pro-apoptotic and
      p53-mediated gene expression (Bcl2l, Bax, Cdkn1a and Bbc3) in mammary epithelial
      cells derived from Sfrp1(-/-) mice. Thus Sfrp1 plays an important role in
      mediating mammary epithelial apoptotic response to DNA damage in vivo. The role
      SFRP1 plays in p53 target gene expression was also noted, which suggests that
      this pathway may be worth exploiting for novel therapies. 

PMID- 24038863
TI  - Not too much reason for excitement: deep brain stimulation for anorexia nervosa.

PMID- 24038864
TI  - Differences in use of complementary and alternative medicine between children and
      adolescents with cancer in Germany: a population based survey.
AB  - BACKGROUND: Use of complementary and alternative medicine (CAM) in children with
      cancer is common and probably increasing. However, data concerning differences
      between children and adolescents focusing on prevalence, reasons for use/non-use,
      costs, adverse effects, and socio-demographic factors are lacking. PROCEDURE: A
      population-based survey over a 1 year period with 497 participants was conducted.
      RESULTS: Of the 457 respondents (92%) 322 were children and 135 adolescents (>16
      years of age) with malignancies. 31% reported CAM use from the time when being
      diagnosed, compared to an overall lifetime prevalence rate of 41% before cancer
      diagnosis. Among CAM users the most prevalent therapies were homeopathy, massage,
      anthroposophic medicine, acupuncture, and Bach flowers. The main reasons for use
      were to reduce therapy-related side effects, to strengthen the immune system, to
      achieve physical stabilization and to increase healing chances. Socio-demographic
      factors associated with CAM use were higher parental education and higher family
      income. A majority of CAM users (97%) would recommend CAM use. Most users (78%)
      informed a physician about CAM use. Side effects were rarely reported (5%), minor
      and self-limiting. CONCLUSIONS: The high prevalence rates seem to represent the
      parental or patients needs for additional treatment perceived as successful and
      devoid of side-effects. Clinical care and the physician-patient relation would
      profit from an enhanced understanding of CAM and a greater candidness towards the
      parental needs. Safety and efficacy - especially of CAM with high prevalence
      rates - should be studied in rigorous basic and clinical research.

PMID- 24038865
TI  - A UV-blocking polymer shell prevents one-photon photoreactions while allowing
      multi-photon processes in encapsulated upconverting nanoparticles.
AB  - Sun block for nanoparticles: Unintentional photorelease triggered by UV light is
      a problem in photodynamic therapy. Encapsulating upconverting nanoparticles
      containing photoswitches in a UV-blocking amphiphilic polymer shuts down the one
      photon process and only allows two-photon-driven photochemistry. Thus, UV light
      is blocked while NIR light can reach the nanoparticle core and trigger
      photorelease. 

PMID- 24038866
TI  - Copper-catalyzed intermolecular regioselective hydroamination of styrenes with
      polymethylhydrosiloxane and hydroxylamines.

PMID- 24038867
TI  - Nrf2/Maf-binding-site-containing functional Cyp6a2 allele is associated with DDT
      resistance in Drosophila melanogaster.
AB  - BACKGROUND: Increased insecticide detoxification mediated by cytochrome P450s is
      a common mechanism of insecticide resistance. Although Cyp6a2 has been observed
      to be overexpressed in many 4,4'-dichlorodiphenyltrichloroethane (DDT)-resistant
      strains of Drosophila melanogaster, how Cyp6a2 is regulated and whether its
      overproduction confers DDT resistance remain elusive. RESULTS: Molecular analysis
      identified five Cyp6a2 alleles (Cyp6a2(Canton) (-S-1) , Cyp6a2(Canton) (-S-2) ,
      Cyp6a2(91-C) , Cyp6a2(91-R) and Cyp6a2(Wisconsin) (-) (WD) ) from four D.
      melanogaster strains, notably differing in the presence or absence of an intact
      Nrf2/Maf (a transcription factor) binding site in the 5'-promoter core region, a
      'G1410' frameshift deletion mutation in the heme-binding region and a long
      terminal repeat (LTR) of transposable element 17.6 in the 3'-untranslated region
      (UTR). Linkage analysis confirmed that DDT resistance was genetically linked to a
      Nrf2/Maf-binding-site-containing, LTR-lacking functional allele of Cyp6a2
      (Cyp6a2(91-R) ). The qRT-PCR results showed that overexpression of functional
      Cyp6a2 was consistently associated with DDT resistance. Luciferase reporter gene
      assays revealed that an intact Nrf2/Maf binding site in the 5'-promoter core
      region enhanced the constitutive transcription of Cyp6a2. CONCLUSION: The results
      suggest that the Nrf2/Maf binding-site-containing functional Cyp6a2 allele is
      associated with DDT resistance in the D. melanogaster strains under study.

PMID- 24038868
TI  - A comparison of polymer and polymer-hydroxyapatite composite tissue engineered
      scaffolds for use in bone regeneration. An in vitro and in vivo study.
AB  - Previous in vitro work demonstrated porous PLA and PLGA both had the mechanical
      strength and sustained the excellent skeletal stem cell (SSC) growth required of
      an osteogenic bonegraft substitute, for use in impaction bone grafting. The
      purpose of this investigation was to assess the effects of the addition of
      hydroxyapatite (HA) to the scaffolds before clinical translation. PLA, PLA+10%
      HA, PLGA, and PLGA+10% HA were milled and impacted into discs before undergoing a
      standardized shear test. Cellular compatibility analysis followed 14 days
      incubation with human skeletal stems cells (SSC). The best two performing
      polymers were taken forward for in vivo analysis. SSC seeded polymer discs were
      implanted subcutaneously in mice. All polymers had superior mechanical shear
      strength compared with allograft (p < 0.01). Excellent SSC survival was
      demonstrated on all polymers, but the PLA polymers showed enhanced osteoblastic
      activity (ALP assay p < 0.01) and collagen-1 formation. In vivo analysis was
      performed on PLA and PLA+10% HA. MicroCT analysis revealed increased bone
      formation on the PLA HA (p < 0.01), and excellent neo-vessel formation in both
      samples. Histology confirmed evidence of de novo bone formation. PLA HA showed
      both enhanced osteoinductive and osteogenic capacity. This polymer composite has
      been selected for scaled-up experimentation before clinical translation.

PMID- 24038869
TI  - Pharmacokinetics of oral dichloroacetate in dogs.
AB  - We characterized the pharmacokinetics and dynamics of dichloroacetate (DCA), an
      investigational drug for mitochondrial diseases, pulmonary arterial hypertension,
      and cancer. Adult Beagle dogs were orally administered 6.25 mg/kg q12h DCA for 4
      weeks. Plasma kinetics was determined after 1, 14, and 28 days. The activity and
      expression of glutathione transferase zeta 1 (GSTZ1), which biotransforms DCA to
      glyoxylate, were determined from liver biopsies at baseline and after 27 days.
      Dogs demonstrate much slower clearance and greater inhibition of DCA metabolism
      and GSTZ1 activity and expression than rodents and most humans. Indeed, the
      plasma kinetics of DCA in dogs is similar to humans with GSTZ1 polymorphisms that
      confer exceptionally slow plasma clearance. Dogs may be a useful model to further
      investigate the toxicokinetics and therapeutic potential of DCA. 

PMID- 24038870
TI  - Interhemispheric differences of fMRI responses to visual stimuli in patients with
      side-fixed migraine aura.
AB  - Migraine sufferers with aura often report photosensitivity and visual discomfort
      outside of attacks and many consider bright or flickering light an attack
      precipitating factor. The nature of this visual hypersensitivity and its relation
      to the underlying pathophysiology of the migraine aura is unknown. Using fMRI
      measurements during visual stimulation we examined the visual cortical
      responsiveness of patients with migraine with aura. We applied a within-patient
      design by assessing functional interhemispheric differences in patients
      consistently experiencing visual aura in the same visual hemifield. We recruited
      20 patients with frequent side-fixed visual aura attacks (>=90% of auras
      occurring in the same visual hemifield) and 20 age and sex matched healthy
      controls and compared the fMRI blood oxygenation level dependent (BOLD) responses
      to visual stimulation between symptomatic and asymptomatic hemispheres during the
      interictal phase and between migraine patients and controls. BOLD responses were
      selectively increased in the symptomatic hemispheres. This was found in the
      inferior parietal lobule (P = 0.002), the inferior frontal gyrus (P = 0.003), and
      the superior parietal lobule (P = 0.017). The affected cortical areas comprise a
      visually driven functional network involved in oculomotor control, guidance of
      movement, motion perception, visual attention, and visual spatial memory. The
      patients also had significantly increased response in the same cortical areas
      when compared to controls (P < 0.05). We discovered a lateralized alteration of a
      visually driven functional network in patients with side-fixed aura. These
      findings suggest a hyperexcitability of the visual system in the interictal phase
      of migraine with visual aura.

PMID- 24038871
TI  - Regulation of mesenchymal-to-epithelial transition by PARAXIS during
      somitogenesis.
AB  - BACKGROUND: Dynamic alterations in cell shape, migration, and adhesion play a
      central role in tissue morphogenesis during embryonic development and congenital
      disease. The mesenchymal-to-epithelial transition that occurs during vertebrate
      somitogenesis is required for proper patterning of the axial musculoskeletal
      system. Somitic MET is initiated in the presomitic mesoderm by PARAXIS-dependent
      changes in cell adhesion, cell polarity, and the composition of the extracellular
      matrix. However, the target genes downstream of the transcription factor PARAXIS
      remain poorly described. RESULTS: A genome-wide comparison of gene expression in
      the anterior presomitic mesoderm and newly formed somites of Paraxis(-/-) embryos
      resulted in a set of deregulated genes enriched for factors associated with
      extracellular matrix and cytoskeletal organization and cell-cell and cell-ECM
      adhesion. The greatest change in expression was seen in fibroblast activation
      protein alpha (Fap), encoding a dipeptidyl peptidase capable of increasing
      fibronectin and collagen fiber organization in extracellular matrix. Further,
      downstream genes in the Wnt and Notch signaling pathways were downregulated,
      predicting that PARAXIS participates in positive feedback loops in both pathways.
      CONCLUSIONS: These data demonstrate that PARAXIS initiates and stabilizes somite
      epithelialization by integrating signals from multiple pathways to control the
      reorganization of the ECM, cytoskeleton, and adhesion junctions during MET.

PMID- 24038872
TI  - Characterization of the key intermediates of carbene-catalyzed umpolung by NMR
      spectroscopy and X-ray diffraction: breslow intermediates, homoenolates, and
      azolium enolates.
AB  - Caught in the act: Diamino enols, diamino dienols, azolium enolates, and azolium
      enols are postulated intermediates of the N-heterocyclic carbene catalyzed
      umpolung of aldehydes and enals. Several of these elusive reaction intermediates
      were generated with the saturated imidazolidin-2-ylidene SIPr (R=2,6-bis(2
      propyl)phenyl) and characterized by NMR spectroscopy and X-ray crystallography. 

PMID- 24038873
TI  - Arylation of diazoesters by a transient N-H insertion organocascade.
AB  - It takes two: A unique organocatalyzed cascade for the unsymmetric double
      arylation of alpha-nitrodiazoesters is described. This organocascade features the
      strategic use of carbene-activating anilines in conjunction with a urea catalyst,
      thus allowing for the synthesis of pharmaceutically attractive alpha-diarylesters
      through a transient N?H insertion process. 

PMID- 24038874
TI  - Use of a readily removable auxiliary group for the synthesis of pyrrolidones by
      the palladium-catalyzed intramolecular amination of unactivated gamma C(sp(3))-H
      bonds.
AB  - Easy on, easy off: Directing groups found to promote the palladium-catalyzed
      amination of gamma C(sp(3) )?H and C(sp(2) )?H bonds of secondary amides included
      5-methoxy-8-aminoquinoline, which can be removed under mild conditions (see
      scheme; CAN=ceric ammonium nitrate). In conjunction with a beta-C?H methylation
      or gamma-C?H arylation step, the gamma-C(sp(3) )?H amination provided access to
      complex pyrrolidones from readily available precursors. 

PMID- 24038875
TI  - Endocrine phenotype of 6q16.1-q21 deletion involving SIM1 and Prader-Willi
      syndrome-like features.
AB  - Proximal interstitial 6q deletion involving Single-minded 1 (SIM1) gene causes a
      syndromic form of obesity mimicking Prader-Willi syndrome. In addition to
      obesity, Prader-Willi syndrome includes several other endocrinopathies, such as
      hypothyroidism, growth hormone deficiency, and hypogonadotropic hypogonadism. The
      endocrine phenotype of interstitial 6q deletion remains largely unknown, although
      clinical similarities between Prader-Willi syndrome and interstitial 6q deletion
      suggest endocrine abnormalities also may contribute to the interstitial 6q
      deletion phenotype. This report describes the endocrine phenotype in a propositus
      with the Prader-Willi-like syndrome associated with an interstitial 6q deletion
      including the SIM1 gene. Detailed endocrine evaluation of the propositus during
      childhood and adolescence revealed hypopituitarism, though initial endocrine
      evaluations during infancy were unremarkable. Our patient raises the possibility
      that hypopituitarism may be part of the phenotype, especially short stature,
      caused by interstitial 6q deletion. SIM1 plays an important role in the
      development of neuroendocrine lineage cells, implicating SIM1 haploinsufficiency
      in the pathophysiology of hypopituitarism seen in our propositus. Early
      identification of endocrine abnormalities can improve clinical outcome by
      allowing timely introduction of hormone replacement therapy. Hence, we suggest
      that detailed endocrine evaluation and longitudinal endocrine follow up be
      performed in individuals with proximal interstitial 6q deletion involving SIM1.

PMID- 24038876
TI  - Invaders: Recognition of Double-Stranded DNA by Using Duplexes Modified with
      Interstrand Zippers of 2'-O-(Pyren-1-yl)methyl-ribonucleotides.
AB  - The invasion has begun: Invaders are shown to recognize DNA hairpins in cell-free
      assays and chromosomal DNA during non-denaturing fluorescence in situ
      hybridization (nd-FISH) experiments. As Invaders are devoid of inherent sequence
      limitations, many previously inaccessible DNA targets could become accessible to
      exogenous control with important ramifications for karyotyping, in vivo imaging,
      and gene regulation.

PMID- 24038878
TI  - Early postnatal growth in children with HLA-conferred susceptibility to type 1
      diabetes.
AB  - AIMS/HYPOTHESIS: An association between increased length/height and weight gain
      and risk of type 1 diabetes (T1D) has been reported in children. We set out to
      investigate the potential contribution of T1D human leukocyte antigen (HLA) risk
      genotypes to this association in two countries with a contrasting disease
      incidence. METHODS: In Estonia and Finland, length and weight were monitored up
      to the age of 24 months in 688 subjects. According to their HLA genotypes, the
      children were divided into four groups, those with very high, high or moderate
      risk for T1D, as well as a neutral/control group. Relative length and weight
      (SDS) were assessed and compared at 3, 6, 12, 18 and 24 months using World Health
      Organization (WHO) growth curves. RESULTS: The mean relative length at the age of
      24 months was lower in the group with the very high risk HLA genotype compared to
      the controls (p < 0.05). The mean relative weight differed between those two
      groups at the age of 12, 18 and 24 months (p < 0.05). When Estonian and Finnish
      cohorts were analyzed separately, the relative length showed similar but non
      significant trends in both countries, while in Estonia the changes in weight at
      some time points still remained significant (p < 0.05). CONCLUSIONS: Children
      with the highest HLA-conferred risk for T1D gained less weight and length during
      the first 24 months of life, and this feature was more pronounced in the Estonian
      children.

PMID- 24038877
TI  - Position of glycine substitutions in the triple helix of COL6A1, COL6A2, and
      COL6A3 is correlated with severity and mode of inheritance in collagen VI
      myopathies.
AB  - Glycine substitutions in the conserved Gly-X-Y motif in the triple helical (TH)
      domain of collagen VI are the most commonly identified mutations in the collagen
      VI myopathies including Ullrich congenital muscular dystrophy, Bethlem myopathy,
      and intermediate (INT) phenotypes. We describe clinical and genetic
      characteristics of 97 individuals with glycine substitutions in the TH domain of
      COL6A1, COL6A2, or COL6A3 and add a review of 97 published cases, for a total of
      194 cases. Clinical findings include severe, INT, and mild phenotypes even from
      patients with identical mutations. INT phenotypes were most common, accounting
      for almost half of patients, emphasizing the importance of INT phenotypes to the
      overall phenotypic spectrum. Glycine substitutions in the TH domain are heavily
      clustered in a short segment N-terminal to the 17th Gly-X-Y triplet, where they
      are acting as dominants. The most severe cases are clustered in an even smaller
      region including Gly-X-Y triplets 10-15, accounting for only 5% of the TH domain.
      Our findings suggest that clustering of glycine substitutions in the N-terminal
      region of collagen VI is not based on features of the primary sequence. We
      hypothesize that this region may represent a functional domain within the triple
      helix. 

PMID- 24038879
TI  - Effect of temperature and grain type on the long-term persistence and efficacy of
      s-methoprene in controlling Rhyzopertha dominica.
AB  - BACKGROUND: The efficacy of methoprene can vary with surface substrates,
      application methods and environmental conditions. The objectives of the present
      study were to examine the effects of temperature and grain type on the long-term
      persistence and efficacy of methoprene in controlling Rhyzopertha dominica from
      Guangzhou, China. RESULTS: Methoprene applied at 1 mg kg(-1) caused >90%
      suppression of F1 adult progeny of R. dominica for 150-270 days. Temperature and
      grain type both influenced the long-term persistence of methoprene. Overall
      multivariate analysis of variance showed that the order of progeny reduction at
      different temperatures ( degrees C) was: 24 > 28 > 32 > 36; the order of the
      progeny reduction on the different grains was: paddy > wheat and maize.
      CONCLUSION: The results of our experiments show the maximum effect of methoprene
      for R. dominica control at 24  degrees C on paddy.

PMID- 24038880
TI  - N-Terminal methylation of proteasome subunit Rpt1 in yeast.
AB  - The 26S proteasome is a multicatalytic protease complex that degrades
      ubiquitinated proteins in eukaryotic cells. It consists of a proteolytic core
      (the 20S proteasome) as well as regulatory particles, which contain six ATPase
      (Rpt) subunits involved in unfolding and translocation of substrates to the
      catalytic chamber of the 20S proteasome. In this study, we used MS to analyze the
      N-terminal modifications of the yeast Rpt1 subunit, which contains the N-terminal
      recognition sequence for N-methyltransferase. Our results revealed that following
      the removal of the initiation Met residue of yeast Rpt1, the N-terminal Pro
      residue is either unmodified, mono-methylated, or di-methylated, and that this N
      methylation has not been conserved throughout evolution. In order to gain a
      better understanding of the possible function(s) of the Pro-Lys (PK) sequence at
      positions 3 and 4 of yeast Rpt1, we generated mutant strains expressing an Rpt1
      allele that lacks this sequence. The absence of the PK sequence abolished N
      methylation, decreased cell growth, and increased sensitivity to stress. Our data
      suggest that N-methylation of Rpt1 and/or its PK sequence might be important in
      cell growth or stress tolerance in yeast. 

PMID- 24038881
TI  - Tissue clearing for optical anatomy.
AB  - Quest for transparency: Detailed optical imaging of complex biological entities
      remains an unmet goal mainly because of the light scattering of biological
      tissue. A new approach to tissue clearing termed CLARITY is getting us closer to
      an anatomical view of thick tissues and entire organs with cellular resolution. 

PMID- 24038882
TI  - Characterizing drought stress and trait influence on maize yield under current
      and future conditions.
AB  - Global climate change is predicted to increase temperatures, alter geographical
      patterns of rainfall and increase the frequency of extreme climatic events. Such
      changes are likely to alter the timing and magnitude of drought stresses
      experienced by crops. This study used new developments in the classification of
      crop water stress to first characterize the typology and frequency of drought
      stress patterns experienced by European maize crops and their associated
      distributions of grain yield, and second determine the influence of the breeding
      traits anthesis-silking synchrony, maturity and kernel number on yield in
      different drought-stress scenarios, under current and future climates. Under
      historical conditions, a low-stress scenario occurred most frequently (ca. 40%),
      and three other stress types exposing crops to late-season stresses each occurred
      in ca. 20% of cases. A key revelation shown was that the four patterns will also
      be the most dominant stress patterns under 2050 conditions. Future frequencies of
      low drought stress were reduced by ca. 15%, and those of severe water deficit
      during grain filling increased from 18% to 25%. Despite this, effects of elevated
      CO2 on crop growth moderated detrimental effects of climate change on yield.
      Increasing anthesis-silking synchrony had the greatest effect on yield in low
      drought-stress seasonal patterns, whereas earlier maturity had the greatest
      effect in crops exposed to severe early-terminal drought stress. Segregating
      drought-stress patterns into key groups allowed greater insight into the effects
      of trait perturbation on crop yield under different weather conditions. We
      demonstrate that for crops exposed to the same drought-stress pattern, trait
      perturbation under current climates will have a similar impact on yield as that
      expected in future, even though the frequencies of severe drought stress will
      increase in future. These results have important ramifications for breeding of
      maize and have implications for studies examining genetic and physiological crop
      responses to environmental stresses. 

PMID- 24038883
TI  - Heat shock protein 32/heme oxygenase-1 protects mouse Sertoli cells from
      hyperthermia-induced apoptosis by CO activation of sGC signalling pathways.
AB  - Heat shock protein 32 (Hsp32)/heme oxygenase-1 (HO-1) may be a key enzyme for the
      protection of cells against stress. Its anti-apoptotic effect has been attributed
      to its product, carbon monoxide (CO), in many types of cells. However, whether
      its anti-apoptotic mechanism plays a role in Sertoli cells (SCs) is not yet
      clear. We hypothesise that Hsp32/HO-1 and CO generated from it provide survival
      advantages in SCs by preventing apoptosis under heat exposure. After treatment of
      cultured SCs with hyperthermia and/or Hsp32/HO-1 activater hemin, apoptosis was
      measured valuated by annexin V-FITC and caspase-3 activation. We have also
      analysed the Hsp32/HO-1-derived CO content of cultured media and cyclic guanosine
      monophosphate (cGMP) production by enzyme-linked immunosorbent assay (ELISA).
      Hyperthermia induced SCs apoptosis, while preincubation with hemin suppressed SC
      hyperthermia-induced apoptosis. Hyperthermia and/or hemin increase Hsp32/HO-1
      gene expression and the production of CO, which, in turn, stimulates the
      generation of cGMP. The results suggest that Hsp32/HO-1 is a protective factor in
      heat-stressed SCs, and that CO generated from Hsp32/HO-1 is involved in the anti
      apoptotic pathway. 

PMID- 24038884
TI  - Ultrasound-mediated synthesis of high-molecular weight polystyrene-grafted silver
      nanoparticles by facile ligand exchange reactions in suspension.
AB  - Ultrasound mediated facile ligand exchange method in suspension for the formation
      of polystyrene-grafted silver nanoparticles is reported. Amazingly, this method
      allows even grafting of very high molecular weight polystyrenes (up to 217 200 g
      mol(-1) ) having a single terminal thiol group at the chain end. Detailed studies
      are carried out to gain insights in the role of molecular weight of the ligands
      and the mechanism of the ligand exchange reactions. Key factors are determined to
      be the droplet formation by ultrasonification and low silver content, which
      enhances the availability of the terminal thiol end group significantly. The
      extraordinary compatibility of the ligand exchange method in particular regarding
      high molecular weights is attributed to hydrophilic orientation of the terminal
      thiol groups at the liquid-liquid interphase. This is proved conclusively by
      using an in situ method as a reference approach in which agglomeration occurs at
      considerably lower molecular weights due to the absence of preferred end group
      orientation within the polymer coil. In homogeneous phase only the chain length
      is found to be the crucial factor in stabilization of silver nanoparticles. 

PMID- 24038885
TI  - How long can folinic acid rescue be delayed after high-dose methotrexate without
      toxicity?
AB  - To determine the optimal time of folinic acid rescue after methotrexate (MTX)
      treatment in patients with ALL, we selected and evaluated relevant studies that
      included doses, rescue delay, and side effects. Rescue at 42-48 hours resulted in
      considerable toxicity, except when low doses of MTX were used (1 g/m(2)) or serum
      MTX levels remained consistently low at 24, 30, and 36 hours. Rescue started at
      30-36 hours was safe. In the absence of evidence that later rescue improves
      prognosis, we suggest that folinic acid rescue (105 mg/m(2)) be started no later
      than 36 hours from the start of MTX (5-6 g/m(2)).

PMID- 24038886
TI  - Estrogen-related receptor ERRalpha regulation of human hydroxysteroid
      sulfotransferase (SULT2A1) gene expression in human Caco-2 cells.
AB  - Human hydroxysteroid sulfotransferase, SULT2A1, is important for xenobiotic
      detoxification and the maintenance of hydroxysteroid homeostasis. Our published
      report suggested that estrogen-related receptor ERRalpha downregulates SULT2A1 in
      Hep G2 cells. The results shown in this study suggest that ERRalpha upregulates
      SULT2A1 transcription in Caco-2 cells. The deletion analysis suggested that
      SULT2A1 promoter region between -65 and -44 is important for this upregulation.
      Our further investigation suggested that ERRalpha binding element, ERRE51,
      mediates ERRalpha activation of SULT2A1 promoter transcription in Caco-2 cells.
      The interaction of ERRE51 with ERRalpha was confirmed by electrophoretic mobility
      shift assay and chromatin immunoprecipitation analysis. Results also suggest that
      the difference of constitutive androstane receptor transcription levels in Hep G2
      and Caco-2 cells at least partially contribute to the cell type dependent
      ERRalpha modulation of SULT2A1 promoter transcription. ERRalpha regulates human
      SULT2A1 transcription by competing with other nuclear receptors binding to the
      DNA-promoter region. 

PMID- 24038887
TI  - Utility of flow cytometry for immunophenotyping double-hit lymphomas.

PMID- 24038888
TI  - Templated hierarchical self-assembly of poly(p-aryltriazole) foldamers.
AB  - A biomimetic approach has been used for the templated self-assembly of a helical
      poly(para-aryltriazole) foldamer. The solvophobic folding process yields helices
      that further self-assemble into long nanotubes (see picture; scale bar: 100 nm).
      Constructs of controlled length and chirality can be generated by applying a
      poly(gamma-benzyl-l-glutamate) scaffold at the appropriate assembly conditions,
      mimicking tobacco mosaic virus self-assembly. 

PMID- 24038889
TI  - Mutation spectrum and genotype-phenotype correlation in Cornelia de Lange
      syndrome.
AB  - Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous
      developmental disorder. Clinical features include growth retardation,
      intellectual disability, limb defects, typical facial dysmorphism, and other
      systemic involvement. The increased understanding of the genetic basis of CdLS
      has led to diagnostic improvement and expansion of the phenotype. Mutations in
      five genes (NIPBL, SMC1A, SMC3, RAD21, and HDAC8), all regulators or structural
      components of cohesin, have been identified. Approximately 60% of CdLS cases are
      due to NIPBL mutations, 5% caused by mutations in SMC1A, RAD21, and HDAC8 and one
      proband was found to carry a mutation in SMC3. To date, 311 CdLS-causing
      mutations are known including missense, nonsense, small deletions and insertions,
      splice site mutations, and genomic rearrangements. Phenotypic variability is seen
      both intra- and intergenically. This article reviews the spectrum of CdLS
      mutations with a particular emphasis on their correlation to the clinical
      phenotype. 

PMID- 24038890
TI  - Pubertal development and fertility in survivors of childhood acute myeloid
      leukemia treated with chemotherapy only: a NOPHO-AML study.
AB  - BACKGROUND: More than 60% of children with acute myeloid leukemia (AML) become
      long-term survivors. Most are cured using chemotherapy without hematopoietic stem
      cell transplantation (HSCT). We report on pubertal development and compare self
      reported parenthood among AML survivors and their siblings. PROCEDURE: We
      included 137 children treated for AML according to the Nordic Society of
      Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, who were
      alive by June 2007. Patients with relapse or treated with HSCT were excluded. AML
      survivors participated in a physical and biochemical examination (n = 102) and
      completed a questionnaire (n = 101). One of their siblings completed an identical
      questionnaire (n = 84). RESULTS: At a median follow-up of 11 years (range 5-25)
      after diagnosis of AML the survivors (median age 16 years, range 5-36) were
      either prepubertal or had entered puberty normally. Serum levels of FSH, LH,
      testosterone, estradiol, sex hormone binding globulin (SHBG), inhibin A and B,
      and testicular volumes were within normal ranges. Anti-Mullerian hormone (AMH)
      levels were decreased in 5 of 40 postpubertal females. Mean reported age at
      menarche was 13.1 (range 11-17) years. Among survivors 15 years of age or older
      31% of females reported pregnancies and 9% of males reported pregnancies in their
      partners, rates comparable with the frequency reported by their siblings.
      CONCLUSIONS: Most AML survivors treated with chemotherapy had normal pubertal
      development and fertility, however, AMH levels were decreased in 13% of
      postpubertal females. Longer follow-up is necessary to evaluate possible risk of
      premature ovarian failure.

PMID- 24038891
TI  - Paravalvular leak closure after transcatheter aortic valve replacement with a
      self-expanding prosthesis.
AB  - INTRODUCTION: Paravalvular leak (PVL) after percutaneous transcatheter aortic
      valve replacement (TAVR) is associated with significant morbidity and mortality.
      Percutaneous PVL closure has been reported for balloon-expandable valves but not
      self-expandable valves. METHODS: We conducted a review of cases at our center
      where patients who received TAVR with self-expandable valves and went on to
      develop severe PVL underwent percutaneous closure. Baseline demographic, TAVR
      procedural, PVL procedural, and follow-up data were collected. RESULTS: A total
      of five patients with severe PVL after TAVR with a self-expanding valve underwent
      percutaneous PVL closure. Four of five patients had a trial of balloon
      postdilatation after valve deployment and had significant persistent PVL. In all
      five patients, PVL went from moderate-severe to mild-moderate PVL. There were no
      adverse events. CONCLUSION: Percutaneous PVL closure for severe PVL self
      expanding valve for TAVR is a safe and efficacious procedure. Procedural
      technique involves transesophageal guidance, a high approach through the valve
      struts, deployment of an appropriate size device, and careful monitoring. This
      method may be part of the algorithm for severe PVL after TAVR.

PMID- 24038892
TI  - Association between suicide method, and gender, age, and education level in Iran
      over 2006-2010.
AB  - INTRODUCTION: We aimed to evaluate the relationship between suicide method, and
      gender, age, and level of education in a nationwide study in Iran over the period
      from 2006 to 2010. METHODS: Data on completed suicide cases referred to all
      forensic medicine centers throughout the country that were approved by an autopsy
      test were collected using data collection forms, which were filled out by the
      family members in interview sessions. Then, statistical analyses were performed
      using analysis of variance and chi-square tests, as well as logistic regression
      analysis. RESULTS: Hanging is more popular among men (62.9% versus 27.7%), while
      self-burning is preferable for women (39% versus 7%) (P < 0.0001). Younger
      individuals more frequently adopt a highly violent method, firearms (mean age of
      27.1), while older persons more often use hanging and poisoning (mean ages of
      32.4 and 32.1, respectively) (P < 0.0001). Hanging and self-burning are more
      frequently used by persons with lower levels of education, whereas poisoning is
      more popular with more educated individuals (P < 0.0001). DISCUSSION: All of the
      studied variables, that is, gender, age, education level, are critical risk
      factors of adopting different suicide methods in an Iranian population. Future
      work is necessary to explore the psychopathology adopting different suicide
      methods in the Iranian population.

PMID- 24038894
TI  - Synthesis and reactivity of metal complexes with acyclic (amino)(ylide)carbene
      ligands.
AB  - No cycle required: The straightforward synthesis of acyclic (amino)(ylide)carbene
      gold complexes was achieved by reaction of isocyanide gold complexes with
      phosphorus and arsenic ylides as well as electron-rich olefins. Their ability to
      form bimetallic species and to act as ligand-transfer reagents has also been
      established. 

PMID- 24038893
TI  - Difluoro(sulfinato)methylation of N-sulfinyl imines facilitated by 2-pyridyl
      sulfone: stereoselective synthesis of difluorinated beta-amino sulfonic acids and
      peptidosulfonamides.

PMID- 24038896
TI  - Surface-induced dechlorination of FeOEP-Cl on Cu(111).
AB  - To be or not to be chlorinated: When octaethylporphyrin iron(III) chloride (FeOEP
      Cl) molecules are sublimated onto Cu(111) surfaces, two different molecular
      species are observed through scanning tunneling microscopy, showing either a
      protrusion or a depression at the center. In combination with van der Waals
      corrected density functional calculations, our experiments reveal that one
      species corresponds to FeOEP-Cl molecules with the chlorine atom pointing away
      from the surface, whereas the other species has been dechlorinated.

PMID- 24038897
TI  - Guidance on the implementation and reporting of a drug safety Bayesian network
      meta-analysis.
AB  - The Drug Information Association Bayesian Scientific Working Group (BSWG) was
      formed in 2011 with a vision to ensure that Bayesian methods are well understood
      and broadly utilized for design and analysis and throughout the medical product
      development process, and to improve industrial, regulatory, and economic decision
      making. The group, composed of individuals from academia, industry, and
      regulatory, has as its mission to facilitate the appropriate use and contribute
      to the progress of Bayesian methodology. In this paper, the safety sub-team of
      the BSWG explores the use of Bayesian methods when applied to drug safety meta
      analysis and network meta-analysis. Guidance is presented on the conduct and
      reporting of such analyses. We also discuss different structural model
      assumptions and provide discussion on prior specification. The work is
      illustrated through a case study involving a network meta-analysis related to the
      cardiovascular safety of non-steroidal anti-inflammatory drugs.

PMID- 24038898
TI  - Synthesis of the macrocyclic core of rhizopodin.

PMID- 24038899
TI  - Classification of fish samples via an integrated proteomics and bioinformatics
      approach.
AB  - There is an increasing demand to develop cost-effective and accurate approaches
      to analyzing biological tissue samples. This is especially relevant in the
      fishing industry where closely related fish samples can be mislabeled, and the
      high market value of certain fish leads to the use of alternative species as
      substitutes, for example, Barramundi and Nile Perch (belonging to the same genus,
      Lates). There is a need to combine selective proteomic datasets with
      sophisticated computational analysis to devise a robust classification approach.
      This paper describes an integrated MS-based proteomics and bioinformatics
      approach to classifying a range of fish samples. A classifier is developed using
      training data that successfully discriminates between Barramundi and Nile Perch
      samples using a selected protein subset of the proteome. Additionally, the
      classifier is shown to successfully discriminate between test samples not used to
      develop the classifier, including samples that have been cooked, and to classify
      other fish species as neither Barramundi nor Nile Perch. This approach has
      applications to truth in labeling for fishmongers and restaurants, monitoring
      fish catches, and for scientific research into distances between species. 

PMID- 24038900
TI  - Synthesis, biological activities and SAR studies of novel 1-Ethyl-7-methyl-4-oxo
      1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid based diacyl and sulfonyl acyl
      hydrazines.
AB  - BACKGROUND: Diacyl hydrazines have attracted significant interest in medicine,
      pesticide chemistry and material science. It is an important class of insect
      growth regulators. In this study, acyl hydrazine, the essential active group was
      incorporated in to nalidixic acid with the aim of combining the active groups to
      generate more potent agrochemical. RESULTS: Various nalidixic acid based diacyl
      and sulphonyl acyl hydrazines derivatives were synthesized and characterized by
      spectral techniques. These compounds were screened for the antifungal activity
      against five pathogenic fungi, nitrification inhibitory activity and insect
      growth regulator (IGR) activity against Spodoptera litura. The fungicidal
      activity was screened against R. bataticola, S. rolfsii, R. solani, F. oxysporum
      and A. porri. Most of the compounds showed moderate to good antifungal activity
      against A. porri (ED50 = 29.6-495.9 ug/mL). All the compounds showed significant
      nitrification inhibitory activity at 5% level. IGR activity was examined by
      feeding method against S. litura. CONCLUSION: The study revealed that a few
      compounds possessed good activity against three different pests namely certain
      fungus, soil bacteria and insect, among which, compound 37 (R' = 4-chlorophenyl)
      behaved the best.

PMID- 24038901
TI  - Medicare beneficiaries most likely to be readmitted.
AB  - Recent legislation requires reducing Medicare payments to hospitals with higher
      than expected 30-day readmission rates, but there is no consensus strategy to
      identify patients who should optimally be targeted with care coordination
      services to mitigate this risk. To determine which hospital and patient factors
      predict variation in all discharge hospital readmission rates, a 5% sample of all
      Medicare fee-for-service beneficiaries with continuous Part A and B coverage was
      examined for the first 9 months of 2008 in combination with other administrative
      data available to the Centers for Medicare and Medicaid Services. We included
      age, sex, race, dual-eligibility status, number of comorbid conditions,
      geographic region, hospital case mix, and reason for entitlement in the multiple
      regression model to assess how they influenced the 30-day readmission rate.
      Beneficiaries with 10 or more chronic conditions were more than 6 times more
      likely to be readmitted than beneficiaries with 1 to 4 chronic conditions. These
      beneficiaries represent only 8.9% of all Medicare beneficiaries (31.0% of all
      hospitalizations), but they were responsible for 50.2% of all readmissions. The
      31.8% of beneficiaries with 5 to 9 chronic conditions (55.5% of all
      hospitalizations) had the second highest odds ratio (2.5) and were responsible
      for 45% of all readmissions.

PMID- 24038903
TI  - Partial trisomy 15q23 and partial monosomy 5p15.32: Case report and a literature
      review.

PMID- 24038904
TI  - Tissue specific oxidative stress profile in relation to glycaemic regulation in
      mice.
AB  - BACKGROUND: Diabetes mellitus is a metabolic disorder characterized by
      hyperglycaemia resulting from uncontrolled glucose regulation. Reactive oxygen
      species are recognized as one link between hyperglycaemia and diabetic
      complications. Studies have shown that diabetes mellitus is associated with
      decreases in antioxidant potential and increased formation of free radicals
      leading to oxidative stress. The present study was undertaken because an
      unequivocal demonstration that control of hyperglycaemia can reduce oxidative
      stress is still lacking. METHODS: In the present study, we investigated oxidative
      stress profile of normal, streptozotocin-induced diabetic, insulin-treated and
      untreated diabetic animals. On the one hand, oxidative damage caused to lipids,
      proteins and DNA was measured. On other hand, antioxidant defense was measured in
      terms of specific activities of antioxidant enzymes (AOEs) and antioxidant
      molecules. RESULTS: It was observed that the damage to lipids, proteins and DNA
      caused by free radicals increased in diabetic animals compared with that in
      controls. In diabetic animals not treated with insulin, damage to all biological
      molecules increased further significantly (p <= 0.005). Changes in AOEs from
      different tissues were complex depicting a varied AOE level in different tissues.
      Insulin treatment significantly improved the oxidative stress profile in all
      tissues studies. CONCLUSIONS: The control of hyperglycaemia improves oxidative
      stress profile, that is, the ability of cells to cope up with oxidative stress.

PMID- 24038902
TI  - Functional characterization and differential coactivation patterns of two
      cytoarchitectonic visual areas on the human posterior fusiform gyrus.
AB  - The ventral stream of the human extrastriate visual cortex shows a considerable
      functional heterogeneity from early visual processing (posterior) to higher,
      domain-specific processing (anterior). The fusiform gyrus hosts several of those
      "high-level" functional areas. We recently found a subdivision of the posterior
      fusiform gyrus on the microstructural level, that is, two distinct
      cytoarchitectonic areas, FG1 and FG2 (Caspers et al., Brain Structure & Function,
      2013). To gain a first insight in the function of these two areas, here we
      studied their behavioral involvement and coactivation patterns by means of meta
      analytic connectivity modeling based on the BrainMap database (www.brainmap.org),
      using probabilistic maps of these areas as seed regions. The coactivation
      patterns of the areas support the concept of a common involvement in a core
      network subserving different cognitive tasks, that is, object recognition, visual
      language perception, or visual attention. In addition, the analysis supports the
      previous cytoarchitectonic parcellation, indicating that FG1 appears as a
      transitional area between early and higher visual cortex and FG2 as a higher
      order one. The latter area is furthermore lateralized, as it shows strong
      relations to the visual language processing system in the left hemisphere, while
      its right side is stronger associated with face selective regions. These findings
      indicate that functional lateralization of area FG2 relies on a different pattern
      of connectivity rather than side-specific cytoarchitectonic features.

PMID- 24038905
TI  - Carbon sequestration potential of soils in southeast Germany derived from stable
      soil organic carbon saturation.
AB  - Sequestration of atmospheric carbon (C) in soils through improved management of
      forest and agricultural land is considered to have high potential for global CO2
      mitigation. However, the potential of soils to sequester soil organic carbon
      (SOC) in a stable form, which is limited by the stabilization of SOC against
      microbial mineralization, is largely unknown. In this study, we estimated the C
      sequestration potential of soils in southeast Germany by calculating the
      potential SOC saturation of silt and clay particles according to Hassink [Plant
      and Soil 191 (1997) 77] on the basis of 516 soil profiles. The determination of
      the current SOC content of silt and clay fractions for major soil units and land
      uses allowed an estimation of the C saturation deficit corresponding to the long
      term C sequestration potential. The results showed that cropland soils have a low
      level of C saturation of around 50% and could store considerable amounts of
      additional SOC. A relatively high C sequestration potential was also determined
      for grassland soils. In contrast, forest soils had a low C sequestration
      potential as they were almost C saturated. A high proportion of sites with a high
      degree of apparent oversaturation revealed that in acidic, coarse-textured soils
      the relation to silt and clay is not suitable to estimate the stable C
      saturation. A strong correlation of the C saturation deficit with temperature and
      precipitation allowed a spatial estimation of the C sequestration potential for
      Bavaria. In total, about 395 Mt CO2 -equivalents could theoretically be stored in
      A horizons of cultivated soils - four times the annual emission of greenhouse
      gases in Bavaria. Although achieving the entire estimated C storage capacity is
      unrealistic, improved management of cultivated land could contribute
      significantly to CO2 mitigation. Moreover, increasing SOC stocks have additional
      benefits with respect to enhanced soil fertility and agricultural productivity. 

PMID- 24038906
TI  - Effect of Spilanthes acmella hydroethanolic extract activity on tumour cell actin
      cytoskeleton.
AB  - Numerous natural products have pharmacological activity such that many
      biologically active compounds have led to the development of cancer chemotherapy
      drugs. Spilanthes acmella (Asteraceae) is widely cultivated in the State of Para,
      Brazil, being employed in folk medicine for its anti-inflammatory, antimicrobial,
      antioxidant, analgesic, insecticide, and larvicidal properties. However, its
      cytotoxicity and influence on actin cytoskeleton organisation in tumour cell
      lines are practically nonexistent. We have verified the cytotoxicity of a
      hydroethanolic extract of the inflorescence of S. acmella, and examined its
      effects on the cytoskeleton of tumour cells. Decreasing concentrations of the
      extract (250, 500 and 1,000 ug/mL) were given to cultures of neoplastic cells
      (HEp-2). Cytotoxicity was assessed by the MTT test, and the influence on
      cytoskeleton organisation was examined by fluorescence microscopy. The IC50 of
      the hydroethanolic extract was 513 ug/mL, confirming the data obtained from the
      MTT assay that gave high cytotoxicity. The actin cytoskeleton arrangement of HEp2
      cells at 500 and 1,000 ug/mL showed depolymerisation of the filaments, causing
      loss of morphology and consequently compromising cell adhesion.

PMID- 24038907
TI  - Rapid and efficient trifluoromethylation of aromatic and heteroaromatic compounds
      using potassium trifluoroacetate enabled by a flow system.
AB  - Going to the source: The trifluoromethylation of aryl/heteroaryl iodides has been
      demonstrated using a flow system, thus enabling a rapid rate of reaction. A broad
      spectrum of trifluoromethylated compounds was prepared in good to excellent
      yields using CF3 CO2 K as the trifluoromethyl source. The process has the
      advantage of short reaction times and uses convenient [CF3 ] sources. 

PMID- 24038908
TI  - Comparison of a new ELISA-based with the flow cytometric assay for vasodilator
      associated stimulated phosphoprotein phosphorylation to assess P2Y12 -inhibition
      after ticagrelor intake.
AB  - BACKGROUND: Ticagrelor is a P2Y12 receptor antagonist, with superior effects but
      also ensuing enhanced bleeding risk as compared to clopidogrel. Determination of
      platelet inhibition may be useful to confirm efficient platelet inhibition on an
      individual patient level and to identify patients at risk for bleeding. The
      vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay
      specifically measures platelet P2Y12 inhibition, but has so far required
      individual sample processing. A new ELISA-based VASP assay has been developed,
      which allows batch analysis after initial platelet activation. Because of the
      reversible binding of ticagrelor it is unclear if the ELISA and flow cytometric
      assays provide comparable results; several washing steps of the ELISA may
      potentially result in false low results through dilution. METHODS: We
      hypothesized that the conventional and new methods may be comparable when
      ticagrelor is used. We pair-wise compared the platelet reactivity index (PRI)
      between assays in a prospective clinical trial. Six healthy volunteers received a
      single 180 mg loading dose of ticagrelor. RESULTS: PRI-values of the two methods
      correlated well (r = 0.97, P < 0.001). Ticagrelor rapidly decreased PRI values on
      average after 50 min, but nadir levels 2-6 h after ticagrelor intake were 15%
      higher when PRI% was measured with the flow cytometric method. Bland-Altman
      analysis showed that the flow cytometric assay measured markedly higher PRI
      levels than the new ELISA-based technique (mean difference 13%). CONCLUSIONS: The
      new ELISA-based VASP assay offers an alternative to the currently used flow
      cytometric method, but measures lower PRI levels, particularly when PRI falls
      below 20% after ticagrelor intake.

PMID- 24038910
TI  - Response to the letter to the editor by M. Elsner et al: "comment on Binhai Ren
      et al (2013;15:28-41). Long term reversal of diabetes in non-obese diabetic mice
      by liver-directed gene therapy".

PMID- 24038909
TI  - RASA1 mutations and associated phenotypes in 68 families with capillary
      malformation-arteriovenous malformation.
AB  - Capillary malformation-arteriovenous malformation (CM-AVM) is an autosomal
      dominant disorder, caused by heterozygous RASA1 mutations, and manifesting
      multifocal CMs and high risk for fast-flow lesions. A limited number of patients
      have been reported, raising the question of the phenotypic borders. We identified
      new patients with a clinical diagnosis of CM-AVM, and patients with overlapping
      phenotypes. RASA1 was screened in 261 index patients with: CM-AVM (n = 100),
      common CM(s) (port-wine stain; n = 100), Sturge-Weber syndrome (n = 37), or
      isolated AVM(s) (n = 24). Fifty-eight distinct RASA1 mutations (43 novel) were
      identified in 68 index patients with CM-AVM and none in patients with other
      phenotypes. A novel clinical feature was identified: cutaneous zones of numerous
      small white pale halos with a central red spot. An additional question addressed
      in this study was the "second-hit" hypothesis as a pathophysiological mechanism
      for CM-AVM. One tissue from a patient with a germline RASA1 mutation was
      available. The analysis of the tissue showed loss of the wild-type RASA1 allele.
      In conclusion, mutations in RASA1 underscore the specific CM-AVM phenotype and
      the clinical diagnosis is based on identifying the characteristic CMs. The high
      incidence of fast-flow lesions warrants careful clinical and radiologic
      examination, and regular follow-up. 

PMID- 24038911
TI  - The impact of main branch restenosis on long term mortality following drug
      eluting stent implantation in patients with de novo unprotected distal left main
      bifurcation coronary lesions: the Milan and New-Tokyo (MITO) Registry.
AB  - BACKGROUND: In-stent restenosis (ISR) remains one of the main limitations for
      percutaneous coronary intervention of unprotected distal left main (UDLM). This
      study aims to demonstrate the impact of main-branch ISR (MB-ISR) on mortality and
      to clarify the optimal strategy. METHODS: Between 2002 and 2008, 482 consecutive
      UDLM patients treated with drug eluting stent (sirolimus and paclitaxel) were
      evaluated. RESULTS: During follow-up period (median 52.6 months), MB-ISR occurred
      in 29, SB-ISR in 65, and MB/SB-ISR in 24. Multivariable analysis demonstrated
      that the independent predictors of MB-ISR were calcification (HR 2.284, p =
      0.016), true-bifurcation (HR 2.331, p = 0.024), insulin-dependent diabetes
      mellitus (insulin-DM) (HR 2.259, p = 0.048). Furthermore, final proximal
      postdilatation (FPPD) (HR 0.548, p = 0.077), full LM cover approach (FCA) (HR
      0.605, p = 0.093) and greater MLD (HR 0.611, p = 0.062) had a tendency to reduce
      MB-ISR. Furthermore, the occurrence of MB-ISR within 1-year was associated with
      cardiac-death (HR 2.734, p = 0.017). CONCLUSIONS: The patients with MB-ISR had
      more comorbidities and complex lesions, resulting in higher risk of cardiac
      mortality as compared to the patients without MB-ISR. Presence of calcification,
      true-bifurcation and insulin-DM were associated with MB-ISR following UDLM
      intervention, while FCA, FPPD, and greater MLD seemed to be associated with the
      low occurrence of MB-ISR.

PMID- 24038912
TI  - Nano-structured polymer-silica composite derived from a marine diatom via
      deactivation enhanced atom transfer radical polymerization grafting.

PMID- 24038914
TI  - Water-stabilized three- and four-atom palladium clusters as highly active
      catalytic species in ligand-free C-C cross-coupling reactions.
AB  - Elite cliques: Palladium clusters with three and four atoms were found to be the
      catalytically active species for ligand-free palladium-catalyzed C?C bond-forming
      reactions. These palladium cluster species could be stabilized in water and
      stored for long periods of time for use on demand with no loss of activity. High
      yields of products and turnover frequencies (TOFs) of up to 10(5)  h(-1) were
      observed. 

PMID- 24038915
TI  - Carbon dioxide as a C1 building block for the formation of carboxylic acids by
      formal catalytic hydrocarboxylation.

PMID- 24038913
TI  - Long-term survival of children less than six years of age enrolled on the CCG-945
      phase III trial for newly-diagnosed high-grade glioma: a report from the
      Children's Oncology Group.
AB  - BACKGROUND: We analyzed the long-term survival of children under 6 years of age
      (<6 years) enrolled upon the Children's Cancer Group (CCG)-945 high-grade glioma
      (HGG) study to determine the impact of intrinsic biological characteristics as
      well as treatment upon both survival and quality of life (QOL) in this younger
      age population. PROCEDURE: Analyses were undertaken on patients <6 years with
      institutionally diagnosed HGG enrolled on the CCG-945 trial. Comparisons of
      survival were performed for patients <3 years of age (<3 years) (treated with
      intent to avoid irradiation) versus those between 3 and 6 years of age (3-6
      years) (treated with irradiation and chemotherapy) at diagnosis. Discordance
      between the institutional diagnoses of HGG and consensus-reviewed diagnoses led
      us to perform further survival analyses for both groups. We compared the two
      groups of patients for biological markers, and evaluated the neuropsychological
      and QOL outcomes of long-term survivors. RESULTS: Patients <3 years (n = 49,
      19.5% of all enrolled patients) at diagnosis had a 10-year EFS and OS of 29 +/-
      6.5% and 37.5 +/- 7%, respectively, while for patients 3-6 years (n = 34, 13.5%
      of all enrolled patients) 10-year EFS and OS were 35 +/- 8% and 36 +/- 8%,
      respectively. Molecular marker analysis showed that a smaller proportion of
      patients <3 years harbored TP53 mutations (P = 0.05). Analysis of QOL outcomes
      with a median length of follow-up of 15.1 years (9.5-19.2) showed comparable
      results. CONCLUSIONS: QOL and survival data were similar for the two groups. A
      larger prospective study is justified to study the efficacy of chemotherapy only
      regimens in younger children.

PMID- 24038916
TI  - Management of disseminated choroid plexus papilloma: a case study.
AB  - Choroid plexus papilloma (CPP) is a low-grade neoplasm of the choroid plexus that
      typically occurs in childhood and comprises under 1% of adult brain tumors. In
      this article, we report our experience delivering craniospinal irradiation (CSI)
      to a highly unusual case of disseminated CPP in an adult patient 8 years after an
      initial near total resection. The patient remains free of disease progression 3
      years after completing radiation.

PMID- 24038917
TI  - Calcium phosphate-reinforced photosensitizer-loaded polymer nanoparticles for
      photodynamic therapy.
AB  - Calcium phosphate-reinforced photosensitizer-loaded polymer nanoparticles have
      been developed for photodynamic therapy. Chlorin e6 (Ce6)-loaded core-shell
      corona polymer micelles of poly(ethylene glycol)-b-poly(L-aspartic acid)-b-poly(L
      phenylalanine) (PEG-PAsp-PPhe) were employed as template nanoparticles for
      mineralization with calcium phosphate (CaP). CaP deposition was performed by the
      electrostatic localization of calcium ions at the anionic PAsp middle shells and
      the subsequent addition of phosphate anions. CaP-reinforced nanoparticles
      exhibited enhanced stability. The CaP mineral layer effectively inhibited Ce6
      release from the Ce6-loaded mineralized nanoparticles (Ce6-NP-CaP) at
      physiological pH value. At an acidic endosomal pH value of 5.0, Ce6 release was
      enhanced, owing to rapid dissolution of the CaP minerals. Upon irradiation of Ce6
      NP-CaP-treated MCF-7 breast-tumor cells, the cell viability dramatically
      decreased with increasing irradiation time. The phototoxicity of Ce6-NP-CaP was
      much higher than that of free Ce6. Non-invasive optical-imaging results indicated
      that Ce6-NP-CaP exhibited enhanced tumor specificity compared with free Ce6 and
      Ce6-loaded non-mineralized polymer nanoparticles (Ce6-NP).

PMID- 24038918
TI  - Hyperbranched polycoumarates with photofunctional multiple shape memory.
AB  - In good shape: The films of hyperbranched polycoumarate derivatives can undergo a
      reversible [2+2] cycloaddition under irradiation of UV light and behave like
      photomechanical elastomers. From a predetermined original shape A the
      photonically and thermally memorized shapes B and C were obtained. The original
      shape was recovered by photoirradiation (see picture; Tg =glass transition
      temperature). 

PMID- 24038919
TI  - Clinical features of depression in Asia: results of a large prospective, cross
      sectional study.
AB  - INTRODUCTION: The objective of this study was to investigate the clinical
      features of depression in Asian patients. METHODS: It was a cross-sectional,
      observational study of depression in China, Korea, Malaysia, Singapore, Taiwan,
      and Thailand. Participants were drug-free outpatients with depressed mood and/or
      anhedonia. Symptoms and clinical features were assessed using the Montgomery
      Asberg Depression Rating Scale, Symptoms Checklist 90-Revised (SCL-90-R), and the
      Fatigue Severity Scale. Other measures included the Medical Outcome Survey 36
      Item Short-Form Health Survey (SF-36), the Sheehan Disability Scale, and the
      Multidimensional Scale of Perceived Social Support (MSPSS). RESULTS: A total of
      547 outpatients with major depressive disorder were included in the analyses.
      Among the Montgomery-Asberg Depression Rating Scale symptoms, "reported sadness"
      and "reduced sleep" had the highest severity, with means (SDs) of 3.4 (1.2) and
      3.4 (1.6), respectively. Apart from the SCL-90-R depression and anxiety domains,
      the SCL-90-R obsession-compulsion syndrome had the highest domain score, with a
      mean (SD) of 1.9 (0.9). Among eight domains, the mean (SD) SF-36 pain subscale
      score of 58.4 (27.7) was only second to that for the SF-36 physical function. In
      comparison to other disability domains, the Sheehan Disability Scale work/school
      had the highest subscale score, with a mean (SD) of 6.5 (2.9). The mean (SD)
      MSPSS "family" subscale score of 4.7 (1.7) was higher than the MSPSS "friends"
      and "significant others" subscale scores. DISCUSSION: This study suggests that
      pain has a minimal impact on the quality of life in Asian patients with
      depression. Noteworthy issues in this population may include insomnia, obsessive
      compulsive symptoms, working/school disability, and family support.

PMID- 24038920
TI  - Pharmaceutically active ionic liquid self-assembled vesicles for the application
      as an efficient drug delivery system.
AB  - Shuttle-drug: Self-assembled vesicles of a pharmaceutically active ionic liquid
      are shown to be an efficient drug delivery system, which realizes the controlled
      release of its pharmaceutically active component directly. 

PMID- 24038921
TI  - Efficacy of insecticide residues on adult Halyomorpha halys (Stal) (Hemiptera:
      Pentatomidae) mortality and injury in apple and peach orchards.
AB  - BACKGROUND: The primary threat from Halyomorpha halys (Stal) (Hemiptera:
      Pentatomidae) originates from populations continuously dispersing from and among
      wild and cultivated hosts, so many individuals may not be directly sprayed with
      insecticides. Limited information exists regarding field-based residual activity
      of insecticides for management of H. halys in tree fruit. Thus, we conducted
      field-based bioassays in apple and peach orchards to evaluate residual activity
      of insecticides commonly applied against H. halys. Adults used in these trials
      were collected from wild and cultivated hosts less than one week prior to testing
      to more accurately reflect the susceptibility of wild H. halys populations in the
      field throughout the season. RESULTS: Significantly higher mortality rates of
      Halyomorpha halys were observed early in the growing season, when overwintered
      adults were prevalent, compared with populations present later in the growing
      season that included new generation adults. Significantly higher mortality was
      recorded for adults exposed to fresh insecticide applications compared with three
      and seven-day old residues. Typically, the addition of an adjuvant did not
      enhance efficacy or residual activity of insecticides. Significantly fewer injury
      sites were recorded on apples treated with dinotefuran and fenpropathrin compared
      with the untreated apples for all residue ages. CONCLUSIONS: Overwintered
      Halyomorpha halys populations are easier to kill with insecticide applications
      than the first and second generation which are present in the field during the
      mid- to late-season. Residual activity of nearly all insecticides decreased
      significantly three days after application and adjuvants generally did not
      increase residual activity. These factors should be considered in developing
      season-long programs for management of this invasive species in tree fruit.

PMID- 24038923
TI  - Allene relay: palladium-catalyzed bicyclization of allene-propargylic carbonates
      with geminal bis(nucleophile)s.

PMID- 24038922
TI  - A practical guide to Bayesian group sequential designs.
AB  - Bayesian approaches to the monitoring of group sequential designs have two main
      advantages compared with classical group sequential designs: first, they
      facilitate implementation of interim success and futility criteria that are
      tailored to the subsequent decision making, and second, they allow inclusion of
      prior information on the treatment difference and on the control group. A general
      class of Bayesian group sequential designs is presented, where multiple criteria
      based on the posterior distribution can be defined to reflect clinically
      meaningful decision criteria on whether to stop or continue the trial at the
      interim analyses. To evaluate the frequentist operating characteristics of these
      designs, both simulation methods and numerical integration methods are proposed,
      as implemented in the corresponding R package gsbDesign. Normal approximations
      are used to allow fast calculation of these characteristics for various
      endpoints. The practical implementation of the approach is illustrated with
      several clinical trial examples from different phases of drug development, with
      various endpoints, and informative priors.

PMID- 24038924
TI  - In vitro evaluation of HPMA-copolymers targeted to HER2 expressing pancreatic
      tumor cells for image guided drug delivery.
AB  - Personalized medicine for the treatment of pancreatic cancer is one potential
      avenue which can prevent the dire outcome of this difficult to treat disease.
      Image guided drug delivery (IGDD) is a method allowing real-time imaging of drug
      therapy in order to predict the potential efficacy and safety of a given
      treatment. Water soluble macromolecular drug carriers such as N-(2
      hydroxypropyl)methacrylamide (HPMA) copolymers provide multifunctional platforms
      for the construction of such IGDD systems. HPMA copolymer conjugates containing
      gemcitabine, a targeting ligand for HER2 receptors overexpressed in some
      pancreatic cancers, and an (111) In(3+) chelating agent are synthesized,
      characterized, and evaluated in vitro for their potential use as an IGDD system
      for pancreatic tumors. The conjugates are capable of binding to pancreatic tumor
      cell lines which express HER2. In vitro drug release is achieved under
      physiological and acidic pH environments. The chelated radioisotopes are stable
      in the presence of mouse serum. The conjugates are effective in killing
      pancreatic tumor cell lines in vitro. These copolymers have potential for further
      preclinical evaluation in pancreatic tumor models. 

PMID- 24038925
TI  - Management of hypogonadism in adolescent girls and adult women with Prader-Willi
      syndrome.
AB  - Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by an
      insatiable appetite, dysmorphic features, cognitive and behavioral difficulties,
      and hypogonadism. The heterogeneous reproductive hormone profiles indicate that
      some PWS women may have symptoms of hypoestrogenism, while others may potentially
      be fertile. We describe our experience in the assessment and treatment of
      hypogonadism in adolescents and adult females with PWS. The study population
      consisted of 20 PWS females, age >=16 years (27.3 +/- 7.9 years), followed in our
      clinic (12 deletion, 7 uniparental disomy, 1 imprinting-center defect). General
      physical examination, pubertal assessment, body mass index (BMI), gynecological
      examination, ultrasonography, bone densitometry, and hormonal profiles [FSH, LH,
      inhibin B, estradiol, prolactin, and TSH] were performed. The relevant assessed
      factors were: FSH and inhibin B, menstrual cycles (oligo/amenorrhea or irregular
      bleeding), ultrasound findings (endometrial thickness, uterine/ovarian
      abnormalities), BMI, bone densitometry, and patient/caregivers attitude. We
      classified seven women with inhibin B >20 ng/ml as potentially fertile. Following
      the assessment of the above factors, we recommended the individual-specific
      treatment; contraceptive pills, intra-uterine device, estrogen/progesterone
      replacement, and cyclic progesterone, in 3, 1, 4, and 1 patients, respectively.
      Four patients did not follow our recommendations due to poor compliance or family
      refusal. We recommended contraception pills for one 26-year-old woman with
      inhibin B and FSH levels 53 ng/ml and 6.4 IU/L; however, she refused treatment,
      conceived spontaneously and had an abortion. Guidelines for hormonal replacement
      therapy in PWS need to be tailored individually depending on physical
      development, hormonal profiles, bone density, and emotional and social needs of
      each PWS adolescent and adult.

PMID- 24038926
TI  - Intact P4 tetrahedra as terminal and bridging ligands in neutral complexes of
      manganese.

PMID- 24038928
TI  - Exercise lowers postprandial glucose but not fasting glucose in type 2 diabetes:
      a meta-analysis of studies using continuous glucose monitoring.
AB  - Exercise has repeatedly been shown to improve glycemic control as assessed by
      glycated hemoglobin. However, changes in glycated hemoglobin do not provide
      information regarding which aspects of glycemic control have been altered. The
      purpose of this systematic review was to examine the effect of exercise as
      assessed by continuous glucose monitoring systems (CGMS) in type 2 diabetes.
      Databases (PubMed, Medline, EMBASE) were searched up to February 2013. Eligible
      studies had participants with type 2 diabetes complete standardized exercise
      protocols and used CGMS to measure changes in glycemic control. Randomized
      controlled trials, crossover trials and studies with pre-post designs were
      included. Average glucose concentration, daily time spent in hyperglycemia or
      hypoglycemia, and fasting glucose concentration were compared between exercise
      and control conditions. Eleven studies met the inclusion criteria and were
      included in the review. Eight studies had short-term (<=2 weeks) exercise
      interventions, whereas three studies had a longer-term intervention (all >2
      months). The types of exercises utilized included aerobic, resistance and a
      combination of the two. The eight short-term studies were included in
      quantitative analysis. Exercise significantly decreased average glucose
      concentrations (-0.8 mmol/L, p < 0.01) and daily time spent in hyperglycemia (
      129 minutes, p < 0.01), but did not significantly affect daily time spent in
      hypoglycemia (-3 minutes, p = 0.47) or fasting glucose (-0.3 mmol/L, p = 0.13).
      The four randomized crossover trials had similar findings compared to studies
      with pre-post designs. Exercise consistently reduced average glucose
      concentrations and time spent in hyperglycemia despite not significantly
      affecting outcomes such as fasting glucose and hypoglycemia.

PMID- 24038927
TI  - Quality collaboratives and campaigns to reduce readmissions: what strategies are
      hospitals using?
AB  - BACKGROUND: Reducing hospital readmissions is a national priority, and many
      hospitals are participating in quality collaboratives or campaigns. OBJECTIVE: To
      describe and compare the current use of hospital strategies to reduce
      readmissions in 2 prominent quality initiatives-STAAR (State Action on Avoidable
      Rehospitalization) and H2H (Hospital-to-Home Campaign). DESIGN: Cross-sectional.
      METHODS: Web-based survey of hospitals that had enrolled in H2H or STAAR from May
      2009 through June 2010, conducted from November 1, 2010 through June 30, 2011 (n
      = 599, response rate of 91%). We used standard frequency analysis and
      multivariable logistic regression to describe differences between STAAR and H2H
      hospitals. RESULTS: Many hospitals were not implementing several of the
      recommended strategies. Although STAAR hospitals tended to be more likely to
      implement several strategies, differences were attenuated when we adjusted for
      region and ownership type. In multivariable models, STAAR hospitals compared with
      H2H hospitals were more likely to ensure outpatient physicians were alerted
      within 48 hours of patient discharge (63% vs 38%, P < 0.001), and more likely to
      provide skilled nursing facilities the direct contact number of the inpatient
      treating physician for patients transferred (53% vs 34%, P = 0.001). H2H
      hospitals were more likely to assign responsibility for medication reconciliation
      to nurses usually or always (80% vs 54%, P = 0.001) and more likely to give most
      or all discharged patients referrals to cardiac rehabilitation services (59% vs
      41%, P = 0.001). CONCLUSIONS: Substantial opportunity for improvement exists for
      hospitals engaged in STAAR or H2H quality initiatives.

PMID- 24038929
TI  - Midterm follow-up results of transcatheter treatment in patients with unroofed
      coronary sinus.
AB  - OBJECTIVE: We present the midterm results of transcatheter treatment of unroofed
      coronary sinus (CS) using the Amplatzer septal occluder. BACKGROUND: The unroofed
      CS is a rare atrial septal defect communicating the left atrium and CS. Surgery
      has been the mainstay of treatment. METHODS: In a 4.5-year period, nine patients
      (five males) with ages ranging from 26 to 69 years (median 39 years) diagnosed
      with an unroofed CS but without a persistent left superior vena cava (LSVC)
      underwent transcatheter treatment. Computerized tomography (CT) was performed in
      eight patients. Transesophageal echocardiography (TEE) was used to monitor the
      procedure. RESULTS: The mean Qp/Qs ratio was 2.4 +/- 1 and mean systolic
      pulmonary artery pressure was 35 +/- 19 mm Hg. An Amplatzer septal occluder was
      deployed in all nine patients. The device was implanted in the defect in one
      patient and at the CS ostium in the other eight patients. The median device size
      used was 22 mm (16-28 mm). The left disc herniated into the CS in the single
      patient in whom the device was implanted within the defect. All patients were
      available for the 3-month follow-up. None had a residual shunt on the 3-month
      follow-up echocardiography. One patient died of a stroke 4.5 months after the
      procedure. At mean follow-up of 42.6 +/- 18.3 months, symptomatic improvement was
      documented in the remaining eight patients. All eight patients had an O2
      saturation above 96%. CONCLUSION: Transcatheter treatment for unroofed CS without
      persistent LSVC using Amplatzer septal occluder is safe and feasible.

PMID- 24038930
TI  - Temperatures and the growth and development of maize and rice: a review.
AB  - Because of global land surface warming, extreme temperature events are expected
      to occur more often and more intensely, affecting the growth and development of
      the major cereal crops in several ways, thus affecting the production component
      of food security. In this study, we have identified rice and maize crop responses
      to temperature in different, but consistent, phenological phases and development
      stages. A literature review and data compilation of around 140 scientific
      articles have determined the key temperature thresholds and response to extreme
      temperature effects for rice and maize, complementing an earlier study on wheat.
      Lethal temperatures and cardinal temperatures, together with error estimates,
      have been identified for phenological phases and development stages. Following
      the methodology of previous work, we have collected and statistically analysed
      temperature thresholds of the three crops for the key physiological processes
      such as leaf initiation, shoot growth and root growth and for the most
      susceptible phenological phases such as sowing to emergence, anthesis and grain
      filling. Our summary shows that cardinal temperatures are conservative between
      studies and are seemingly well defined in all three crops. Anthesis and ripening
      are the most sensitive temperature stages in rice as well as in wheat and maize.
      We call for further experimental studies of the effects of transgressing
      threshold temperatures so such responses can be included into crop impact and
      adaptation models. 

PMID- 24038931
TI  - Comment on Binhai Ren et al. (2013; 15: 28-41): long-term reversal of diabetes in
      non-obese diabetic mice by liver-directed gene therapy.

PMID- 24038932
TI  - Development of superficial white matter and its structural interplay with
      cortical gray matter in children and adolescents.
AB  - Healthy human brain undergoes significant changes during development. The
      developmental trajectory of superficial white matter (SWM) is less understood
      relative to cortical gray matter (GM) and deep white matter. In this study, a
      multimodal imaging strategy was applied to vertexwise map SWM microstructure and
      cortical thickness to characterize their developmental pattern and elucidate SWM
      GM associations in children and adolescents. Microscopic changes in SWM were
      evaluated with water diffusion parameters including fractional anisotropy (FA),
      mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in 133
      healthy subjects aged 10-18 years. Results demonstrated distinct maturational
      patterns in SWM and GM. SWM showed increasing FA and decreasing MD and RD
      underneath bilateral motor sensory cortices and superior temporal auditory
      cortex, suggesting increasing myelination. A second developmental pattern in SWM
      was increasing FA and AD in bilateral orbitofrontal regions and insula,
      suggesting improved axonal coherence. These SWM patterns diverge from the more
      widespread GM maturation, suggesting that cortical thickness changes in
      adolescence are not explained by the encroachment of SWM myelin into the GM-WM
      boundary. Interestingly, age-independent intrinsic association between SWM and
      cortical GM seems to follow functional organization of polymodal and unimodal
      brain regions. Unimodal sensory areas showed positive correlation between GM
      thickness and FA whereas polymodal regions showed negative correlation. Axonal
      coherence and differences in interstitial neuron composition between unimodal and
      polymodal regions may account for these SWM-GM association patterns. Intrinsic
      SWM-GM relationships unveiled by neuroimaging in vivo can be useful for examining
      psychiatric disorders with known WM/GM disturbances.

PMID- 24038933
TI  - Distinct mechanisms of DNA sensing based on N-doped carbon nanotubes with
      enhanced conductance and chemical selectivity.
AB  - N-doped capped carbon nanotube (CNT) electrodes applied to DNA sequencing are
      studied by first-principles calculations. For the face-on nucleobase junction
      configurations, a conventional conductance ordering is obtained where the largest
      signal results from guanine according to its high highest occupied molecular
      orbital (HOMO) level, whereas for the edge-on counterparts a distinct conductance
      ordering is observed where the low-HOMO thymine provides the largest signal. The
      edge-on mode is shown to operate based on a novel molecular sensing mechanism
      that reflects the chemical connectivity between N-doped CNT caps that can act
      both as electron donors and electron acceptors and DNA functional groups that
      include the hyperconjugated thymine methyl group. 

PMID- 24038934
TI  - Cobalt molybdenum oxynitrides: synthesis, structural characterization, and
      catalytic activity for the oxygen reduction reaction.

PMID- 24038935
TI  - Rapid determination of catecholamines in urine samples by nonaqueous microchip
      electrophoresis with LIF detection.
AB  - A method was developed for the rapid separation of catecholamines by nonaqueous
      microchip electrophoresis (NAMCE) with LIF detection, A homemade pump-free
      negative pressure sampling device was used for rapid bias-free sampling in NAMCE,
      the injection time was 0.5 s and the electrophoresis separation conditions were
      optimized. Under the optimized conditions, the samples were separated completely
      in <1 min. The average migration times of the epinephrine (E), dopamine (DA), and
      norepinephrine (NE) were 34.26, 43.81, and 50.07 s, with an RSD of 1.05, 1.26,
      and 0.89% (n = 7), respectively. The linearity of the method ranged from 0.0125
      to 2.0 mg/L for E and 0.025~4.0 mg/L for DA and NE, with correlation coefficients
      ranging between 0.9978 and 0.9986. The detection limits of E, DA, and NE were
      2.5, 5.0, and 5.0 MUg/L, respectively. The recoveries of E, DA, and NE in spiked
      urine samples were between 86 and 103%, with RSDs of 4.5~6.8% (n = 5). The
      proposed NAMCE with LIF detection combined with a pump-free negative pressure
      sampling device is a simple, inexpensive, energy efficient, miniaturized system
      that can be successfully applied for the determination of catecholamines in urine
      samples.

PMID- 24038936
TI  - Clinical significance of de novo and inherited copy-number variation.
AB  - Copy-number variations (CNVs) are a common cause of intellectual disability
      and/or multiple congenital anomalies (ID/MCA). However, the clinical
      interpretation of CNVs remains challenging, especially for inherited CNVs. Well
      phenotyped patients (5,531) with ID/MCA were screened for rare CNVs using a 250K
      single-nucleotide polymorphism array platform in order to improve the
      understanding of the contribution of CNVs to a patients phenotype. We detected
      1,663 rare CNVs in 1,388 patients (25.1%; range 0-5 per patient) of which 437
      occurred de novo and 638 were inherited. The detected CNVs were analyzed for
      various characteristics, gene content, and genotype-phenotype correlations.
      Patients with severe phenotypes, including organ malformations, had more de novo
      CNVs (P < 0.001), whereas patient groups with milder phenotypes, such as facial
      dysmorphisms, were enriched for both de novo and inherited CNVs (P < 0.001),
      indicating that not only de novo but also inherited CNVs can be associated with a
      clinically relevant phenotype. Moreover, patients with multiple CNVs presented
      with a more severe phenotype than patients with a single CNV (P < 0.001),
      pointing to a combinatorial effect of the additional CNVs. In addition, we
      identified 20 de novo single-gene CNVs that directly indicate novel genes for
      ID/MCA, including ZFHX4, ANKH, DLG2, MPP7, CEP89, TRIO, ASTN2, and PIK3C3. 

PMID- 24038937
TI  - One size does not fit all--bacterial cell death by antibiotics cannot be
      explained by the action of reactive oxygen species.
AB  - Back to square one: Two recent studies prove that reactive oxygen species (ROS)
      are not responsible for bacterial cell death after treatment with antibiotics.
      The ROS concept cannot be generalized to explain all processes resulting in cell
      death. The search for the mechanism of action of bacterial antibiotics must thus
      return to the beginning. 

PMID- 24038938
TI  - Association of TP53 polymorphisms on the risk of Wilms tumor.
AB  - BACKGROUND: Molecular factors influencing Wilms tumor (WT) development remain
      largely unknown. TP53 mutations seem to be restricted to the anaplastic WT
      subtype. However, TP53 polymorphisms do not have a defined role in the disease.
      PROCEDURE: To assess the impact of TP53 mutations and polymorphisms (PIN2, PIN3,
      and PEX4) on risk of development, age at diagnosis, and survival in WT, we
      analyzed 46 blood DNA samples and 31 fresh tumor DNA samples from 52 patients
      with WT. Sequencing of TP53 exons 2-11 was performed. RESULTS: Tumor DNA analysis
      revealed TP53 pathogenic missense mutations (p.V197M, p.R213Q, p.R248W, and
      p.R337C) in four samples (12.9%). Blood DNA samples revealed a novel intronic
      mutation, IVS2 + 37C > T, in one patient (2.2%). Bilaterality was associated with
      a twofold decrease in survival (P = 0.00037). Diffuse anaplasia also presented a
      lower survival probability compared to patients with non-anaplastic tumors, or
      with focal anaplasia (P = 0.045). Patients with a TP53 somatic mutation showed
      survival probability of 37.5% versus 85.0% for patients with no somatic
      mutations, although the difference was not statistically significant (P =
      0.0706). PIN3 duplicated allele was associated with a 20-month later mean age at
      diagnosis (P = 0.0084). TP53 PEX4 C allele showed an increased risk for WT
      development (P = 0.0379). No relationship was found between survival and gender,
      age at diagnosis, or the less frequent alleles of PIN2, PIN3, and PEX4.
      CONCLUSIONS: Our results demonstrate an association between PIN3 and age at
      diagnosis, as well as an association of PEX4 and risk of development of WT.

PMID- 24038939
TI  - Tailored design and synthesis of heparan sulfate oligosaccharide analogues using
      sequential one-pot multienzyme systems.

PMID- 24038940
TI  - Thieno-pyrrole-fused BODIPY intermediate as a platform to multifunctional NIR
      agents.
AB  - We report the synthesis, photophysical and electrochemical properties, and in
      vivo fluorescence imaging of a series of new thieno-pyrrole-fused near-infrared
      (NIR) BODIPY agents by using a versatile intermediate as a building block. The
      versatile thieno-pyrrole-fused BODIPY intermediate was rationally designed to
      bear bromo-substituents and absorb in the mid-red region (635 nm) to act as an
      organic electrophile for the development of NIR multifunctional agents. The use
      of subsequent palladium-catalyzed and nucleophilic substitution reactions
      afforded highly conjugated NIR BODIPYs. The novel BODIPYs exhibit long-wavelength
      absorptions in the NIR region (650-840 nm). The agents produce sharp fluorescence
      bands, and most of them display respectable quantum yields of fluorescence (0.05
      0.87) useful for biomedical imaging, as demonstrated by in vivo imaging with
      SBDPiR740. Interestingly, a number of agents in the series that are non
      halogenated were reactive to O2 at the triplet photo-excited state coupled with a
      favorable redox potential and decent fluorescence, and hence could be potential
      candidates for use as photosensitizers in fluorescence-guided photodynamic
      therapy. Furthermore, the synthetic approach allows further functionalization of
      the highly conjugated NIR BODIPYs to tune the excited states (PET, ICT) and to
      conjugate targeting moieties for enhanced biological applications.

PMID- 24038941
TI  - Hard X-ray spectroscopic nano-imaging of hierarchical functional materials at
      work.
AB  - Heterogeneous catalysts often consist of an active metal (oxide) in close contact
      with a support material and various promoter elements. Although macroscopic
      properties, such as activity, selectivity and stability, can be assessed with
      catalyst performance testing, the development of relevant, preferably
      quantitative structure-performance relationships require the use of advanced
      characterisation methods. Spectroscopic imaging in the hard X-ray region with
      nanometer-scale resolution has very recently emerged as a powerful approach to
      elucidate the hierarchical structure and related chemistry of catalytic solids in
      action under realistic reaction conditions. This X-ray-based chemical imaging
      method benefits from the combination of high resolution (~30 nm) with large X-ray
      penetration and depth of focus, and the possibility for probing large areas with
      mosaic imaging. These capabilities make it possible to obtain spatial and
      temporal information on chemical changes in catalytic solids as well as a wide
      variety of other functional materials, such as fuel cells and batteries, in their
      full complexity and integrity. In this concept article we provide details on the
      method and setup of full-field hard X-ray spectroscopic imaging, illustrate its
      potential for spatiotemporal chemical imaging by making use of recent showcases,
      outline the pros and cons of this experimental approach and discuss some future
      directions for hierarchical functional materials research. 

PMID- 24038943
TI  - Synthesis of meso-substituted tetrabenzotriazaporphyrins: easy access to hybrid
      macrocycles.

PMID- 24038942
TI  - Response to Wu et al.

PMID- 24038944
TI  - Suspected piperacillin-tazobactam induced nephrotoxicity in the pediatric
      oncology population.
AB  - Neutropenic fever is a common complication of myelosuppressive therapy in
      pediatric oncology patients. Piperacillin-tazobactam (PIP/TAZO) is a broad
      spectrum antibiotic used for empiric treatment of neutropenic fever. We describe
      four cases of suspected PIP/TAZO induced nephrotoxicity occurring in children
      with pediatric malignancies admitted to the hospital and treated for fever +/-
      neutropenia. All patients exhibited acute renal injury shortly after PIP/TAZO
      administration with one of these cases having biopsy evidence of acute
      interstitial nephritis. These findings are suggestive of PIP/TAZO induced
      nephrotoxicity in pediatric oncology patients with fever +/- neutropenia and that
      PIP/TAZO should be used judiciously in this population.

PMID- 24038945
TI  - The development of the asparagus miner (Ophiomyia simplex Loew; Diptera:
      Agromyzidae) in temperate zones: a degree-day model.
AB  - BACKGROUND: The asparagus miner is a putative vector of Fusarium spp., which have
      been implicated in globally declining asparagus production. Growers currently
      apply broad-spectrum insecticides for the asparagus miner, but lack management
      guidelines for adequately controlling the pest. Our aims were (1) to determine
      the lower developmental threshold of the asparagus miner, (2) develop and
      validate a degree-day model describing its phenology, and (3) create a
      developmental time budget for the asparagus miner to help guide growers'
      management decisions. RESULTS: We found that the lower developmental threshold
      for the asparagus miner was 12.1  degrees C, and that the phenology of the
      asparagus miner could be reliably predicted over the course of a two-year study.
      Predictions from the model match well with previously published information on
      the bionomics of the asparagus miner, but fit better for sampling data collected
      from the midwestern and eastern United States than for the United Kingdom. The
      life cycle of the asparagus miner likely requires between 1500 and 2000 degree
      days to complete; the longest developmental time requirement was for the pupal
      stagen CONCLUSION: This study provides tools for the targeted management of the
      asparagus miner by offering a degree-day model that may be used to predict its
      life stages in the north-eastern United States.

PMID- 24038946
TI  - Organocatalytic asymmetric synthesis of propargylamines with two adjacent
      stereocenters: mannich-type reactions of in situ generated C-alkynyl imines with
      beta-keto esters.
AB  - Side by side: The title reaction is catalyzed by the chiral Bronsted acid (S)-1,
      and affords hitherto less accessible chiral propargylamines, having two adjacent
      stereocenters, in good to excellent diastereo- and enantioselectivities. Boc=tert
      butoxycarbonyl. 

PMID- 24038947
TI  - De novo 13q deletions in two patients with mild anorectal malformations as part
      of VATER/VACTERL and VATER/VACTERL-like association and analysis of EFNB2 in
      patients with anorectal malformations.
AB  - Anorectal malformations (ARMs) comprise a broad spectrum of conditions ranging
      from mild anal anomalies to complex cloacal malformations. In 40-50% of cases,
      ARM occurs within the context of defined genetic syndromes or complex multiple
      congenital anomalies, such as VATER/VACTERL (vertebral defects [V], ARMs [A],
      cardiac defects [C], tracheoesophageal fistula with or without esophageal atresia
      [TE], renal malformations [R], and limb defects [L]) association. Here, we report
      the identification of deletions at chromosome 13q using single nucleotide
      polymorphism-based array analysis in two patients with mild ARM as part of
      VATER/VACTERL and VATER/VACTERL-like associations. Both deletions overlap the
      previously defined critical region for ARM. Heterozygous Efnb2 murine knockout
      models presenting with mild ARM suggest EFNB2 as an excellent candidate gene in
      this region. Our patients showed a mild ARM phenotype, closely resembling that of
      the mouse. We performed a comprehensive mutation analysis of the EFNB2 gene in
      331 patients with isolated ARM, or ARM as part of VATER/VACTERL or VATER/VACTERL
      like associations. However, we did not identify any disease-causing mutations.
      Given the convincing argument for EFNB2 as a candidate gene for ARM, analyses of
      larger samples and screening of functionally relevant non-coding regions of EFNB2
      are warranted. In conclusion, our report underlines the association of chromosome
      13q deletions with ARM, suggesting that routine molecular diagnostic workup
      should include the search for these deletions. Despite the negative results of
      our mutation screening, we still consider EFNB2 an excellent candidate gene for
      contributing to the development of ARM in humans.

PMID- 24038948
TI  - HPIP is upregulated in liver cancer and promotes hepatoma cell proliferation via
      activation of G2/M transition.
AB  - Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein
      (HPIP) has been shown to play a role in cancer development and progression.
      However, the detailed role of HPIP in cancer cell growth and the exact mechanism
      by which HPIP regulates cancer cell proliferation remains unclear. Here, we
      report that HPIP is overexpressed in most of 328 liver cancer patients and
      regulates hepatoma cell proliferation through G2/M checkpoint activation. HPIP
      increased anchorage-dependent and -independent growth of human liver cancer cell
      lines. The amino acid region 531-631 of HPIP was important for its modulation of
      liver cancer cell growth. The increased effects of HPIP on liver cancer cell
      proliferation were associated with activation of the G2/M cell-cycle concomitant
      with a marked increase of cyclin B1 and the inhibition of the negative G2/M phase
      regulator GADD45alpha. HPIP knockdown dramatically suppressed the growth of HepG2
      liver cancer cells in nude mice. These data highlight the important role of HPIP
      in liver cancer cell growth and suggest that HPIP may be a good target for liver
      cancer therapy.

PMID- 24038949
TI  - Greater BOLD response to working memory in endurance-trained adults revealed by
      breath-hold calibration.
AB  - BACKGROUND: Cardiorespiratory fitness is associated with increased frontal and
      parietal activation during executive function tasks. While these findings suggest
      fitness-related enhancement of neuronal response, the utility of functional
      magnetic resonance imaging (fMRI) may be limited by potential fitness-related
      differences in global vascular reactivity. The aim of this study was to determine
      if highly fit adults display differential activation during working memory after
      calibration for vascular reactivity relative to their sedentary counterparts.
      METHODS: Thirty-two endurance-trained and 24 sedentary adults, aged 40-65 years,
      completed a 2-Back verbal working memory task and a breath-hold challenge during
      fMRI. Group differences in blood oxygen level-dependent (BOLD) response during
      working memory were examined across the whole brain and in a priori regions of
      interest (ROI) before and after breath-hold calibration using non-parametric
      permutation testing. Multiple regression was used to explore the association
      between cardiorespiratory fitness (VO2 max), age, and calibrated 2-Back-related
      activation within the one a priori ROI with significant group effects. RESULTS:
      In comparison to the endurance-trained group, the sedentary group exhibited
      greater BOLD signal changes in response to the breath-hold task. After, but not
      before calibration, the endurance-trained group displayed significantly higher 2
      Back-related activation in the right middle frontal gyrus (P = 0.049). Older age
      predicted lower 2-Back-related activation (beta = -0.308, P = 0.031), whereas
      fitness predicted higher activation (beta = 0.372, P = 0.021) in this region.
      CONCLUSIONS: Breath-hold calibration increased detection of working memory
      related BOLD response differences between sedentary and endurance-trained adults.
      Moreover, cardiorespiratory fitness appeared to mitigate age-related changes in
      BOLD during working memory in this region.

PMID- 24038950
TI  - Surface modification of PLLA nano-scaffolds with laminin multilayer by LbL
      assembly for enhancing neurite outgrowth.
AB  - In this study, PLLA nanofibers are fabricated by electrospinning and their
      surfaces are modified by laminin/chitosan (LN/CS) polyelectrolyte multilayer.
      Surface C/N ratio determined by XPS analysis quantitatively indicates of discrete
      coating layers on the nanofibers. The amount of LN deposited sustainably
      increases with LbL assembly processing, approximately 60 ng mm(-2) LN per cycle
      of LN/CS deposition. The LN-modified PLLA scaffolds significantly induce neurite
      outgrowth of DRG neurons and NSC compared to the pure PLLA nanofibrous scaffolds.
      Furthermore, higher amounts of LN adsorbed assist in promoting cell proliferation
      than PLLA as-spun nanofibers. Therefore, a facile and efficient method to modify
      nano-scaffolds for the construction of a biomimetic scaffold to promote highly
      efficient neurite outgrowth is presented. 

PMID- 24038951
TI  - "Valve in valve" implantation of two self-expandable transcatheter aortic valves
      in a patient with aortic root aneurysm and massive aortic regurgitation: "a new
      TAVI option".
AB  - Catheter-based treatment of aortic regurgitation (AR) often proves challenging
      especially due to associated anatomical difficulties. Here, we present a case of
      CoreValve implantation with a novel use of the valve-in-valve technique to
      effectively treat severe AR in a patient with repeated cardiac surgery and
      aneurismatic prosthetic ascending aorta.

PMID- 24038952
TI  - Human pharmacokinetics of xanthohumol, an antihyperglycemic flavonoid from hops.
AB  - SCOPE: Xanthohumol (XN) is a bioactive prenylflavonoid from hops. A single-dose
      pharmacokinetic (PK) study was conducted in men (n = 24) and women (n = 24) to
      determine dose-concentration relationships. METHODS AND RESULTS: Subjects
      received a single oral dose of 20, 60, or 180 mg XN. Blood was collected at 0,
      0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, and 120 h. Plasma levels of XN and its
      metabolites, isoxanthohumol (IX), 8-prenylnaringenin (8PN), and 6
      prenylnaringenin (6PN) were measured by LC-MS/MS. Xanthohumol (XN) and IX
      conjugates were dominant circulating flavonoids among all subjects. Levels of 8PN
      and 6PN were undetectable in most subjects. The XN PK profile showed peak
      concentrations around 1 h and between 4-5 h after ingestion. The maximum XN
      concentrations (C(max)) were 33 +/- 7 mg/L, 48 +/- 11 mg/L, and 120 +/- 24 mg/L
      for the 20, 60, and 180 mg dose, respectively. Using noncompartmental modeling,
      the area under the curves (AUC(0->infinity)) for XN were 92 +/- 68 h * MUg/L, 323
      +/- 160 h * MUg/L, and 863 +/- 388 h * MUg/L for the 20, 60, and 180 mg dose,
      respectively. The mean half-life of XN was 20 h for the 60 and 18 h for the 180
      mg dose. CONCLUSION: XN has a distinct biphasic absorption pattern with XN and IX
      conjugates being the major circulating metabolites.

PMID- 24038953
TI  - Single-molecule analysis of the recognition forces underlying nucleo-cytoplasmic
      transport.

PMID- 24038954
TI  - Development of novel tumor-targeted theranostic nanoparticles activated by
      membrane-type matrix metalloproteinases for combined cancer magnetic resonance
      imaging and therapy.
AB  - A major drawback with current cancer therapy is the prevalence of unrequired dose
      limiting toxicity to non-cancerous tissues and organs, which is further
      compounded by a limited ability to rapidly and easily monitor drug delivery,
      pharmacodynamics and therapeutic response. In this report, the design and
      characterization of novel multifunctional "theranostic" nanoparticles (TNPs) is
      described for enzyme-specific drug activation at tumor sites and simultaneous in
      vivo magnetic resonance imaging (MRI) of drug delivery. TNPs are synthesized by
      conjugation of FDA-approved iron oxide nanoparticles ferumoxytol to an MMP
      activatable peptide conjugate of azademethylcolchicine (ICT), creating CLIO-ICTs
      (TNPs). Significant cell death is observed in TNP-treated MMP-14 positive MMTV
      PyMT breast cancer cells in vitro, but not MMP-14 negative fibroblasts or cells
      treated with ferumoxytol alone. Intravenous administration of TNPs to MMTV-PyMT
      tumor-bearing mice and subsequent MRI demonstrates significant tumor selective
      accumulation of the TNP, an observation confirmed by histopathology. Treatment
      with CLIO-ICTs induces a significant antitumor effect and tumor necrosis, a
      response not observed with ferumoxytol. Furthermore, no toxicity or cell death is
      observed in normal tissues following treatment with CLIO-ICTs, ICT, or
      ferumoxytol. These findings demonstrate proof of concept for a new nanotemplate
      that integrates tumor specificity, drug delivery and in vivo imaging into a
      single TNP entity through attachment of enzyme-activated prodrugs onto magnetic
      nanoparticles. This novel approach holds the potential to significantly improve
      targeted cancer therapies, and ultimately enable personalized therapy regimens. 

PMID- 24038955
TI  - Glutathione-sensitive RGD-poly(ethylene glycol)-SS-polyethylenimine for
      intracranial glioblastoma targeted gene delivery.
AB  - BACKGROUND: Reductively reversible and hydrolytically degradable cationic
      polymers have been used as gene delivery systems. The present study aimed to
      enhance the low transfection efficiency caused by PEGylation by taking advantage
      of a nonviral vector containing a disulfide linkage. METHODS: The novel reducible
      targeted gene vector c(RGDyK)-poly(ethylene glycol)-SS-polyethylenimine (RGD-PEG
      SS-PEI), representing a combination of RGD-PEG with PEI through a disulfide
      linkage, was synthesized and its reduction-sensitivity was tested in the presence
      of glutathione. The RGD-PEG-SS-PEI/pDNA complexes were formed and their stability
      was evaluated by agarose gel electrophoresis in both phosphate-buffered saline
      and Dulbecco's modified Eagle's medium with 10% serum. In vitro transfection
      efficiency and cell viability assay of the different polymers was performed for
      U87 cells using pEGFP-N2 and pGL4.2 reporter gene systems. RGD-PEG-SS-PEI/pDsRED
      N1 and RGD-PEG-PEI/pDsRED-N1 complexes were injected intravenously into the U87
      cell-bearing nude mice via their tail vein to investigate in vivo gene
      expression. RESULTS: RGD-PEG-SS-PEI has been synthesized successfully and its
      reduction-sensitivity was confirmed in the presence of glutathione. The RGD-PEG
      SS-PEI/pDNA complexes demonstrated good stability in both conditions. In
      comparison with mPEG-PEI/pDNA for gene delivery, the RGD-PEG-SS-PEI/pDNA complex
      provided improved levels of transfection efficiency and reduced cytotoxicity when
      tested in U87 cells in vitro, and also enhanced levels of gene expression in the
      brains of intracranial U87 glioblastoma-bearing mice as demonstrated using dsRed
      gene transfer and bioimaging in vivo. CONCLUSIONS: The results of the present
      study suggest that RGD-PEG-SS-PEI represents a promising candidate for further
      study in glioblastoma and combined gene therapies.

PMID- 24038956
TI  - Organ-on-a-chip technology and microfluidic whole-body models for pharmacokinetic
      drug toxicity screening.
AB  - Microscale cell culture platforms better mimic the in vivo cellular
      microenvironment than conventional, macroscale systems. Microscale cultures
      therefore elicit a more authentic response from cultured cells, enabling
      physiologically realistic in vitro tissue models to be constructed. The
      fabrication of interconnecting microchambers and microchannels allows drug
      absorption, distribution, metabolism and elimination to be simulated, and enables
      precise manipulation of fluid flow to replicate blood circulation. Complex, multi
      organ interactions can be investigated using "organ-on-a-chip" toxicology
      screens. By reproducing the dynamics of multi-organ interaction, the dynamics of
      various diseases and drug activities can be studied in mechanistic detail. In
      this review, we summarize the current status of technologies related to
      pharmacokinetic-based drug toxicity testing, and the use of microtechnology for
      reproducing the interaction between multiple organs. 

PMID- 24038957
TI  - Topology and membrane anchoring of the lysosomal storage disease-related protein
      CLN5.
AB  - One late infantile variant of the neurodegenerative disease neuronal ceroid
      lipofuscinosis (NCL) is caused by a mutation in the CLN5 gene. CLN5 encodes a
      lysosomal glycoprotein whose structure and function have not yet been clearly
      defined. In the present study, we used epitope-tagged CLN5 to determine the
      topology and solubility of the CLN5 protein. Our results indicated that CLN5 is
      synthesized as a type II transmembrane (TM) glycoprotein with a cytoplasmic N
      terminus, one TM segment, and a large luminal C-terminal domain containing an
      amphipathic helix (AH). The cytoplasmic and TM domains were rapidly removed
      following signal-peptide cleavage, and the resulting mature CLN5 was tightly
      associated with the lumen of the membrane through the AH. CLN5 pathological
      mutants deprived of AH lose their membrane association, are retained in the
      endoplasmic reticulum, and are rapidly degraded by the proteasomal machinery. We
      experimentally define the topology of CLN5 and demonstrate the existence of an AH
      that anchors the protein to the membrane. Our work sheds light on the basic
      properties of CLN5 required to better understand its biological functions and
      involvement in NCL pathogenesis. 

PMID- 24038958
TI  - Fused spirocyclic imidazolone ketals.

PMID- 24038959
TI  - Optimization of reaction conditions towards multiple types of framework isomers
      and periodic-increased porosity: luminescence properties and selective CO2
      adsorption over N2.
AB  - Three new metal-organic frameworks (MOFs) were prepared by
      solvo(hydro)thermolysis and further characterized as framework isomers. The
      structural transformation from non-porous to porous MOFs and the purity of these
      products can be modulated by controlling the reaction temperature. The periodic
      increased porosity observed was further confirmed by CO2 adsorption isotherms.
      Owing to the presence of acylamide groups in the pore walls and the flexible
      nature of the skeleton of these MOFs, highly selective CO2 adsorption over N2 was
      observed, as well as structure-dependent periodic varieties in luminescence
      properties. 

PMID- 24038961
TI  - Merging synthesis and enantioselective functionalization of indoles by a gold
      catalyzed asymmetric cascade reaction.

PMID- 24038960
TI  - PedsQLTM Multidimensional Fatigue Scale in sickle cell disease: feasibility,
      reliability, and validity.
AB  - BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder
      characterized by a chronic hemolytic anemia that can contribute to fatigue and
      global cognitive impairment in patients. The study objective was to report on the
      feasibility, reliability, and validity of the PedsQLTM Multidimensional Fatigue
      Scale in SCD for pediatric patient self-report ages 5-18 years and parent proxy
      report for ages 2-18 years. PROCEDURE: This was a cross-sectional multi-site
      study whereby 240 pediatric patients with SCD and 303 parents completed the 18
      item PedsQLTM Multidimensional Fatigue Scale. Participants also completed the
      PedsQLTM 4.0 Generic Core Scales. RESULTS: The PedsQLTM Multidimensional Fatigue
      Scale evidenced excellent feasibility, excellent reliability for the Total Scale
      Scores (patient self-report alpha = 0.90; parent proxy-report alpha = 0.95), and
      acceptable reliability for the three individual scales (patient self-report alpha
      = 0.77-0.84; parent proxy-report alpha = 0.90-0.97). Intercorrelations of the
      PedsQLTM Multidimensional Fatigue Scale with the PedsQLTM Generic Core Scales
      were predominantly in the large (>=0.50) range, supporting construct validity.
      PedsQLTM Multidimensional Fatigue Scale Scores were significantly worse with
      large effects sizes (>=0.80) for patients with SCD than for a comparison sample
      of healthy children, supporting known-groups discriminant validity. Confirmatory
      factor analysis demonstrated an acceptable to excellent model fit in SCD.
      CONCLUSIONS: The PedsQLTM Multidimensional Fatigue Scale demonstrated acceptable
      to excellent measurement properties in SCD. The results demonstrate the relative
      severity of fatigue symptoms in pediatric patients with SCD, indicating the
      potential clinical utility of multidimensional assessment of fatigue in patients
      with SCD in clinical research and practice.

PMID- 24038963
TI  - Flow cytometric quantification of intraperitoneal free tumor cells (FTC) in
      patients with peritoneal metastasis.
AB  - Background: Peritoneal metastasis (PM) is the most life-threatening type of
      metastasis in abdominal malignancy. To improve the diagnostic accuracy of
      cytologic detection (CY) of free tumor cells (FTC) in the peritoneal cavity, we
      tried to quantify the FTC to leukocyte ratio using flow cytometry in patients
      with peritoneal metastasis. Methods: Cells were recovered from ascites or
      peritoneal lavages from 106 patients who underwent abdominal surgery and
      additional 89 samples which were obtained from peritoneal catheter or access port
      in patients with PM (+) gastric cancer. The cells were immunostained with
      monoclonal antibodies to CD45 and to CD326 (EpCAM). Using flow cytometry, CD326
      (+) and CD45 (+) cells were classified as either tumor cells (T) or leukocytes
      (L) and the T/L ratio (TLR) was calculated. Results: In 106 samples obtained by
      laparotomy, Median (M) of the TLR of PM (+) patients was 1.39% (0-807.87%) which
      was significantly higher than PM (-) patients (M=0%, 0-2.14%, p<0.001). In PM (+)
      patients, 86 CY (+) samples showed higher TLR than 61 CY (-) samples (M=2.81%,
      0.02-1868.44% vs. M=0%, 0-3.45%, p<0.0001). In all of the 24 patients who were
      monitored for TLR before and after intraperitoneal chemotherapy, the TLR was
      reduced which was more dramatic than the results of the change in cytology.
      Conclusion: TLR measured with FACS is an excellent reflection of the tumor spread
      in the peritoneal cavity and could be a reliable diagnostic biomarker to
      determine the severity of PM as well as effectiveness of IP chemotherapy. (c)
      2013 Clinical Cytometry Society.

PMID- 24038962
TI  - Robust structure and reactivity of aqueous arsenous acid-platinum(II) anticancer
      complexes.

PMID- 24038964
TI  - Palladium-catalyzed asymmetric hydrogenation of alpha-acyloxy-1-arylethanones.
AB  - First hand: The first example of a palladium-catalyzed asymmetric hydrogenation
      of alpha-acyloxy ketones (1) was accomplished to give the hydrogenated products 2
      with by far the highest catalytic efficiency in up to quantitative conversions
      and excellent enantioselectivities. The hydrogenated products could serve as
      important intermediates for the preparation of many drug candidates. TFE=2,2,2
      trifluoroethanol. 

PMID- 24038965
TI  - Highly enantioselective aza-Diels-Alder reaction of 1-azadienes with
      enecarbamates catalyzed by chiral phosphoric acids.
AB  - On demand: A highly enantio- and diastereoselective synthesis of 6-amino-
      trisubstituted tetrahydropyridine compounds has been developed through the
      inverse-electron-demand aza-Diels-Alder reaction of N-aryl alpha,beta-unsaturated
      ketimines with enecarbamates (E)-1. Chiral phosphoric acid catalysts achieve
      simultaneous activation of both the 1-azadiene and dienophile partners. 

PMID- 24038966
TI  - Mechanistic insight into the CO2 capture by amidophosphoranes: interplay of the
      ring strain and the trans influence determines the reactivity of the frustrated
      Lewis pairs.
AB  - CO2 capture has attracted increasing attention owing to its contribution to
      global warming and climate change as a greenhouse gas. As an alternative strategy
      to transition-metal-based chemistry and catalysis, frustrated Lewis pairs have
      been developed to sequester CO2 efficiently under mild conditions. However, the
      mechanism of CO2 sequestration with amidophosphoranes remains unclear. Herein, we
      present a thorough density functional theory study on a series of
      amidophosphoranes. Our results reveal that the interplay of the ring strain and
      the trans influence determines the reactivities, thus opening a new avenue to the
      design of frustrated Lewis pairs for CO2 capture. 

PMID- 24038967
TI  - Ten-year follow-up of pediatric patients with non-Hodgkin lymphoma treated with
      allogeneic or autologous stem cell transplantation.
AB  - BACKGROUND: Autologous or allogeneic hematopoietic stem cell transplant (SCT) is
      often considered in patients with relapsed or refractory non-Hodgkin lymphoma
      (NHL) but there are limited data on the use of SCT for the treatment of NHL in
      the pediatric setting. PROCEDURE: To evaluate the role of SCT for children with
      NHL, we reviewed 36 consecutive pediatric patients with NHL who underwent an
      allogeneic (n = 21) or autologous (n = 15) SCT at our institution between 1982
      and 2004. Pathologic classification included: lymphoblastic lymphoma (n = 12),
      Burkitt lymphoma (BL) (n = 5), diffuse large B-cell lymphoma (n = 4), anaplastic
      large cell lymphoma (ALCL) (n = 13), peripheral T cell lymphoma (n = 1), and
      undifferentiated NHL (n = 1). Donor source for allogeneic-SCT recipients was an
      HLA-matched related donor (n = 15), a matched unrelated donor (n = 4), or a
      mismatched donor (related n = 1; unrelated n = 1). Twenty-eight patients (78%)
      had chemotherapy responsive disease at the time of transplant (either CR or PR).
      RESULTS: Overall survival (OS) and disease-free survival (DFS) were 55% and 53%
      with a median follow-up of 9.75 years. Outcomes were similar in patients
      receiving autologous and allogeneic-SCT (DFS 53% in both groups). Patients with
      ALCL had a DFS of 76.9%. In contrast, of five patients transplanted for BL, none
      survived. DFS among patients with chemotherapy sensitive disease was 61%,
      compared with 25% among patients with relapsed/refractory disease (P = 0.019).
      CONCLUSIONS: Allogeneic and autologous SCT offer the prospect of durable, disease
      free survival for a significant proportion of pediatric patients with relapsed or
      refractory NHL. Survival is superior among patients with chemotherapy sensitive
      disease.

PMID- 24038968
TI  - Pre-existing brain states predict aesthetic judgments.
AB  - Intuition and an assumption of basic rationality would suggest that people
      evaluate a stimulus on the basis of its properties and their underlying utility.
      However, various findings suggest that evaluations often depend not only on what
      is being evaluated, but also on contextual factors. Here we demonstrate a further
      departure from normative decision making: Aesthetic evaluations of abstract
      fractal art by human subjects were predicted from pre-stimulus patterns of BOLD
      fMRI signals across a distributed network of frontal regions before the stimuli
      were presented. This predictive power was dissociated from motor biases in favor
      of pressing a particular button to indicate one's choice. Our findings suggest
      that endogenous neural signals present before stimulation can bias decisions at
      multiple levels of representation when evaluating stimuli.

PMID- 24038969
TI  - Development and characterization of a PHB-HV-based 3D scaffold for a tissue
      engineering and cell-therapy combinatorial approach for spinal cord injury
      regeneration.
AB  - Spinal cord injury (SCI) leads to devastating neurological deficits. Several
      tissue engineering (TE)-based approaches have been investigated for repairing
      this condition. Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB-HV) is found
      to be particularly attractive for TE applications due to its properties, such as
      biodegradability, biocompatibility, thermoplasticity and piezoelectricity. Hence,
      this report addresses the development and characterization of PHB-HV-based 3D
      scaffolds, produced by freeze-drying, aimed to SCI treatment. The obtained
      scaffolds reveal an anisotropic morphology with a fully interconnected network of
      pores. In vitro studies demonstrate a lack of cytotoxic effect of PHB-HV
      scaffolds. Direct contact assays also reveal their ability to support the culture
      of CNS-derived cells and mesenchymal-like stem cells from different sources.
      Finally, histocompatibility studies show that PHB-HV scaffolds are well tolerated
      by the host tissue, and do not negatively impact the left hindlimb locomotor
      function recovery. Therefore results herein presented suggest that PHB-HV
      scaffolds may be suitable for SCI treatment. 

PMID- 24038970
TI  - Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple
      sclerosis.
AB  - Cognitive dysfunction is common in patients with multiple sclerosis (MS).
      Saccadic eye movement paradigms such as antisaccades (AS) can sensitively
      interrogate cognitive function, in particular, the executive and attentional
      processes of response selection and inhibition. Although we have previously
      demonstrated significant deficits in the generation of AS in MS patients, the
      neuropathological changes underlying these deficits were not elucidated. In this
      study, 24 patients with relapsing-remitting MS underwent testing using an AS
      paradigm. Rank correlation and multiple regression analyses were subsequently
      used to determine whether AS errors in these patients were associated with: (i)
      neurological and radiological abnormalities, as measured by standard clinical
      techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral
      white and gray-matter damage. Although AS error rates in MS patients did not
      correlate with clinical disability (using the Expanded Disability Status Score),
      T2 lesion load or brain parenchymal fraction, AS error rate did correlate with
      performance on the Paced Auditory Serial Addition Task and the Symbol Digit
      Modalities Test, neuropsychological tests commonly used in MS. Further, voxel
      wise regression analyses revealed associations between AS errors and reduced
      fractional anisotropy throughout most of the cerebellum, and increased mean
      diffusivity in the cerebellar vermis. Region-wise regression analyses confirmed
      that AS errors also correlated with gray-matter atrophy in the cerebellum right
      VI subregion. These results support the use of the AS paradigm as a marker for
      cognitive dysfunction in MS and implicate structural and microstructural changes
      to the cerebellum as a contributing mechanism for AS deficits in these patients.

PMID- 24038971
TI  - Neuromotor synapses in Escobar syndrome.
AB  - The Escobar variant of multiple pterygium syndrome (OMIM #265000) is a rare,
      autosomal recessive disorder associated with mutations in the gamma-subunit of
      the nicotinic acetylcholine receptor (CHRNG). CHRNG is expressed in fetal muscle
      during motor development and contributes to the formation of neuromuscular
      junctions (NMJs). Anomalies in NMJ structure and function have not been
      investigated in patients with Escobar syndrome. We report five patients
      identified as having Escobar syndrome, from four families. In three families, the
      same mutation (c.459dupA) was identified in CHRNG. A biopsy from brachioradialis
      muscle was collected from a patient from one of these families and analyzed for
      NMJ organization using fluorescence microscopy. Compared to spinalis muscle from
      control patients with idiopathic scoliosis or cerebral palsy (CP), the patient
      with Escobar syndrome had a significantly higher degree of acetylcholine receptor
      present outside acetylcholinesterase and significantly less acetylcholinesterase
      outside acetylcholine receptors. Given the role of the acetylcholine receptor
      gamma-subunit in fetal neuromuscular signal transduction and in establishing the
      primary encounter of muscle and motor nerve terminal, the CHRNG mutations
      described in Escobar syndrome may cause a broader disruption of postsynaptic
      proteins and result in aberrant development of the NMJ due to impaired prenatal
      neuromuscular transmission and/or abnormal neuromuscular synaptogenesis.

PMID- 24038972
TI  - Residual SYNTAX score for left main intervention: Are we really ready to predict
      the future?

PMID- 24038973
TI  - Complete vs. incomplete coronary revascularization: waiting for Godot....

PMID- 24038974
TI  - Score this one.

PMID- 24038975
TI  - Refining the "crush".

PMID- 24038976
TI  - Realigning Venus and Mars: the sexual equality of STEMI patients.

PMID- 24038977
TI  - Interventions for acute coronary syndrome in young women and oral contraceptives.

PMID- 24038978
TI  - Roadmaps show the way: coregistration to enhance structural heart interventions.

PMID- 24038979
TI  - Treatment of pulmonary artery stenosis with stent implantation improves distal
      pulmonary artery growth.

PMID- 24038980
TI  - CTO of the SFA: what is the best approach?

PMID- 24038981
TI  - Low profile vascular plugs for paravalvular leaks after TAVR.
AB  - BACKGROUND: Paravalvular leak (PVL) after transcatheter aortic valve replacement
      (TAVR) is associated with less good outcomes. The use of percutaneous plugs is
      among the strategies to treat PVL after TAVR. Plugs have been limited by the need
      to pass 4-6 F delivery sheaths between the TAVR stent frame and the native valve
      leaflets. METHODS: The study population consists of six patients who had at least
      moderate aortic insufficiency (AI), and also developed symptoms of heart failure
      after TAVR. We describe in detail the use of low profile vascular plugs that
      require crossing the leaks with only a 4 F diagnostic catheter. RESULTS: Low
      profile vascular plugs were successfully deployed in all six patients without
      significant complications. Fluoroscopy time ranged 16.7-69.4 min (44.8 +/- 18.8
      min). Contrast volume ranged 15-100 mL (45 +/- 34 mL). One plug was used in five,
      and two adjacent plus in one case. AI severity was reduced from moderate or
      severe to mild or less in four patients, from severe to moderate in one, and in
      one, there was no change. Five of six patients were treated electively and were
      significantly improved in terms of both echocardiographic PVL and also symptoms.
      The one who did not have echocardiographic improvement did not improve clinically
      and expired one month later. CONCLUSIONS: PVL closure can be consistently
      accomplished after TAVR with low profile vascular plugs. Careful analysis of PVL
      location on echo before closure greatly facilitates finding the fluoroscopic
      location of the leak. Decreases in PVL severity are associated with significant
      clinical improvement.

PMID- 24038982
TI  - Incorporating adaptive responses into future projections of coral bleaching.
AB  - Climate warming threatens to increase mass coral bleaching events, and several
      studies have projected the demise of tropical coral reefs this century. However,
      recent evidence indicates corals may be able to respond to thermal stress though
      adaptive processes (e.g., genetic adaptation, acclimatization, and symbiont
      shuffling). How these mechanisms might influence warming-induced bleaching
      remains largely unknown. This study compared how different adaptive processes
      could affect coral bleaching projections. We used the latest bias-corrected
      global sea surface temperature (SST) output from the NOAA/GFDL Earth System Model
      2 (ESM2M) for the preindustrial period through 2100 to project coral bleaching
      trajectories. Initial results showed that, in the absence of adaptive processes,
      application of a preindustrial climatology to the NOAA Coral Reef Watch bleaching
      prediction method overpredicts the present-day bleaching frequency. This suggests
      that corals may have already responded adaptively to some warming over the
      industrial period. We then modified the prediction method so that the bleaching
      threshold either permanently increased in response to thermal history (e.g.,
      simulating directional genetic selection) or temporarily increased for 2-10 years
      in response to a bleaching event (e.g., simulating symbiont shuffling). A
      bleaching threshold that changes relative to the preceding 60 years of thermal
      history reduced the frequency of mass bleaching events by 20-80% compared with
      the 'no adaptive response' prediction model by 2100, depending on the emissions
      scenario. When both types of adaptive responses were applied, up to 14% more reef
      cells avoided high-frequency bleaching by 2100. However, temporary increases in
      bleaching thresholds alone only delayed the occurrence of high-frequency
      bleaching by ca. 10 years in all but the lowest emissions scenario. Future
      research should test the rate and limit of different adaptive responses for coral
      species across latitudes and ocean basins to determine if and how much corals can
      respond to increasing thermal stress.

PMID- 24038983
TI  - Coupling biocatalysis with molecular imprinting in a biomimetic sensor.
AB  - Make it simple: A molecularly imprinted electropolymer was combined with an
      enzyme in a catalytic biomimetic sensor that enabled interference-free detection
      of the drug aminopyrine (AP) at submicromolar concentrations in the presence of
      ascorbic acid and uric acid within 15 s. The sensor functioned by the peroxide
      dependent conversion of AP in a layer above a product-imprinted electropolymer on
      an indicator electrode. 

PMID- 24038984
TI  - Vitamin D2 from UVB light exposed mushrooms modulates immune response to LPS in
      rats.
AB  - SCOPE: Poor vitamin D (vitD) status is linked to increased risk of infectious
      diseases, thus there is need for vitD-rich foods. UVB-exposed mushrooms
      synthesize vitD2 but knowledge of bioavailability and function in immune response
      is lacking. METHODS AND RESULTS: One hundred rats were fed one of five diets-
      control, 20 IU vitD3/day; no vitD3/day; 5% unexposed mushroom, 2.4 IU vitD2/day;
      2.5% UVB mushroom, 300 IU vitD2/day; and 5% UVB mushroom, 600 IU vitD2/day--for
      10 wk and challenged with either saline or the endotoxin LPS. Blood and tissues
      were collected at 3 h postchallenge. Plasma 25-hydroxyvitamin D (25OHD) levels
      from UVB-exposed mushroom fed rats were significantly elevated and associated
      with higher natural killer cell activity and reduced plasma inflammatory response
      to LPS compared to control diet fed rats. Microarray evaluation of rat spleens
      for changes in inflammatory gene expression showed significant upregulation of
      proinflammatory genes after LPS compared to saline controls in all groups.
      However, compared to control rats, upregulation of the proinflammatory genes was
      markedly reduced in the groups fed vitD2-enriched mushrooms. CONCLUSION: Rats fed
      UVB-exposed mushrooms had significantly higher plasma total 25OHD levels that
      were associated with increased innate immune response and anti-inflammatory
      effects.

PMID- 24038986
TI  - Incorrect error-rate control in the multiplicity-adjusted two one-sided tests
      procedure proposed by Zheng, Wang, and Zhao (2012): a counterexample.

PMID- 24038985
TI  - Active targeting using HER-2-affibody-conjugated nanoparticles enabled sensitive
      and specific imaging of orthotopic HER-2 positive ovarian tumors.
AB  - Despite advances in cancer diagnosis and treatment, ovarian cancer remains one of
      the most fatal cancer types. The development of targeted nanoparticle imaging
      probes and therapeutics offers promising approaches for early detection and
      effective treatment of ovarian cancer. In this study, HER-2 targeted magnetic
      iron oxide nanoparticles (IONPs) are developed by conjugating a high affinity and
      small size HER-2 affibody that is labeled with a unique near infrared dye (NIR
      830) to the nanoparticles. Using a clinically relevant orthotopic human ovarian
      tumor xenograft model, it is shown that HER-2 targeted IONPs are selectively
      delivered into both primary and disseminated ovarian tumors, enabling non
      invasive optical and MR imaging of the tumors as small as 1 mm in the peritoneal
      cavity. It is determined that HER-2 targeted delivery of the IONPs is essential
      for specific and sensitive imaging of the HER-2 positive tumor since we are
      unable to detect the imaging signal in the tumors following systemic delivery of
      non-targeted IONPs into the mice bearing HER-2 positive SKOV3 tumors.
      Furthermore, imaging signals and the IONPs are not detected in HER-2 low
      expressing OVCAR3 tumors after systemic delivery of HER-2 targeted-IONPs. Since
      HER-2 is expressed in a high percentage of ovarian cancers, the HER-2 targeted
      dual imaging modality IONPs have potential for the development of novel targeted
      imaging and therapeutic nanoparticles for ovarian cancer detection, targeted drug
      delivery, and image-guided therapy and surgery. 

PMID- 24038987
TI  - Cu/MgAl(2)O(4) as bifunctional catalyst for aldol condensation of 5
      hydroxymethylfurfural and selective transfer hydrogenation.
AB  - Copper supported on mesoporous magnesium aluminate has been prepared as noble
      metal-free solid catalyst for aldol condensation of 5-hydroxymethylfurfural with
      acetone, followed by hydrogenation of the aldol condensation products. The
      investigated mesoporous spinels possess high activity as solid-base catalysts.
      Magnesium aluminate exhibits superior activity compared to zinc and cobalt-based
      aluminates, reaching full conversion and up to 81 % yield of the 1:1 aldol
      product. The high activity can be correlated to a higher concentration of basic
      surface sites on magnesium aluminate. Applying continuous regeneration, the
      catalysts can be recycled without loss of activity. Focusing on the subsequent
      hydrogenation of aldol condensation products, Cu/MgAl2 O4 allows a selective
      hydrogenation and C?O bond cleavage, delivering 3-hydroxybutyl-5-methylfuran as
      the main product with up to 84 % selectivity avoiding ring saturation. Analysis
      of the hydrogenation activity reveals that the reaction proceeds in the following
      order: C?C>C?O>C?O cleavage>ring hydrogenation. Comparable activity and
      selectivity can be also achieved utilizing 2-propanol as solvent in the transfer
      hydrogenation, providing the possibility for partial recycling of acetone and
      optimization of the hydrogen management. 

PMID- 24038988
TI  - Thermoplastic fluorescent conjugated polymers: benefits of preventing pi-pi
      stacking.

PMID- 24038989
TI  - A potential carcinogenic pyrene derivative under Forster resonance energy
      transfer to various energy acceptors in nanoscopic environments.
AB  - Picosecond-resolved Forster resonance energy transfer (FRET) from various
      vibronic bands in benzo[a]pyrene (BP) shows a strong dependency on the spectral
      overlap of an energy acceptor in a confined environment. Our study on the dipolar
      interactions between BP and different acceptors, including ethidium (Et),
      acridine orange (AO), and crystal violet (CV), at the surface of a model anionic
      micelle revealed that the Forster distance (R0) and the rate of energy transfer
      is dependent on the individual spectral overlap of the vibronic bands of BP with
      the absorption spectra of the different energy acceptors. The differential
      behavior of the vibronic bands is compared with that of different dyes [quantum
      dots (QDs)] in a "dye-blend" (mixture) under FRET to an energy acceptor.
      Comparison of the FRET of the QDs with that of BP confirmed the independent
      nature of the dipolar interaction of the vibronic bands with other organic
      molecules, and the use of deconvolution techniques in the interpretation of the
      donor-acceptor (D-A) distance was also justified. We also showed that the
      consideration of differential FRET from the vibronic bands of BP and from the QDs
      in the dye-blend is equally acceptable in theoretical frameworks including the
      Infelta-Tachiya model and D-A distribution analysis in nanoenvironments.

PMID- 24038990
TI  - Interleukin-15 gene therapy and the mammalian target of rapamycin inhibitor
      everolimus inhibit the growth of metastatic breast cancer.
AB  - BACKGROUND: Novel methods to control and treat metastatic breast cancer are
      needed. Interleukin (IL)-15 is a promising cytokine for cancer immunotherapy, and
      everolimus is an orally administered mammalian target of rapamycin (mTOR)
      inhibitor, which is already approved for cancer treatment. In the present study,
      we investigated the efficacy of IL-15 gene therapy and explored the possibility
      of combining IL-15 therapy with everolimus to treat metastatic breast cancer.
      METHODS: A plasmid encoding IL-15 and everolimus were given to mice inoculated
      with 4 T1 mouse breast cancer cells. Tumor size and metastasis were monitored to
      assess the effect of different treatment regimens. Immunohistochemistry was used
      to detect CD4+, CD8+ and NKG2D+ cells and also the expression of Ki-67 in tumor
      tissue; these analyses helped establish the immunization status and tumor
      proliferation rate of different treatment groups. Terminal deoxynucleotidyl
      transferase dUTP nick end labeling assays were performed to assess cellular
      apoptosis in tumor tissues. RESULTS: Both IL-15 and everolimus significantly
      decreased tumor size. IL-15 gene therapy increased the proportion of CD4+ T and
      natural killer (NK) cells but had no effect on CD8+ T cells. By contrast,
      everolimus decreased the number of CD8+ T cells but had no effect on CD4+ T and
      NK cells compared to the control group. Both IL-15 and everolimus decreased
      expression of Ki-67 and increased rates of apoptosis. Although effective on their
      own, no synergistic effect was observed with a combined treatment of everolimus
      and IL-15 gene therapy. CONCLUSIONS: IL-15 gene therapy was potentially useful
      for the treatment of metastatic breast cancer. The possibility of combining
      immunotherapy with everolimus requires further study.

PMID- 24038991
TI  - Synthesis and characterization of a two-coordinate manganese complex and its
      reaction with molecular hydrogen at room temperature.

PMID- 24038992
TI  - Neuroblastoma in older children, adolescents and young adults: a report from the
      International Neuroblastoma Risk Group project.
AB  - BACKGROUND: Neuroblastoma in older children and adolescents has a distinctive,
      indolent phenotype, but little is known about the clinical and biological
      characteristics that distinguish this rare subgroup. Our goal was to determine if
      an optimal age cut-off exists that defines indolent disease and if accepted
      prognostic factors and treatment approaches are applicable to older children.
      PROCEDURE: Using data from the International Neuroblastoma Risk Group, among
      patients >=18 months old (n = 4,027), monthly age cut-offs were tested to
      determine the effect of age on survival. The prognostic effect of baseline
      characteristics and autologous hematopoietic cell transplant (AHCT) for advanced
      disease was assessed within two age cohorts; >=5 to <10 years (n = 730) and >=10
      years (n = 200). RESULTS: Older age was prognostic of poor survival, with outcome
      gradually worsening with increasing age at diagnosis, without statistical
      evidence for an optimal age cut-off beyond 18 months. Among patients >=5 years,
      factors significantly prognostic of lower event-free survival (EFS) and overall
      survival (OS) in multivariable analyses were INSS stage 4, MYCN amplification and
      unfavorable INPC histology classification. Among stage 4 patients, AHCT provided
      a significant EFS and OS benefit. Following relapse, patients in both older
      cohorts had prolonged OS compared to those >=18 months to <5 years (P < 0.0001).
      CONCLUSIONS: Despite indolent disease and infrequent MYCN amplification, older
      children with advanced disease have poor survival, without evidence for a
      specific age cut-off. Our data suggest that AHCT may provide a survival benefit
      in older children with advanced disease. Novel therapeutic approaches are
      required to more effectively treat these patients.

PMID- 24038995
TI  - Opioid non-IgE mediated effects in a BAT assay on drug hypersensitivity to
      pholcodine.

PMID- 24038994
TI  - The critical effect of the countercation in the direct cupration of fluoroform
      with [Cu(OR)2 ](-).
AB  - Just a spectator or a key player? The alkali-metal counterion (K(+) ) plays a
      remarkable key role in the recently discovered cupration reaction of fluoroform
      with dialkoxycuprates. A total of eight Lewis acid and Lewis base centers
      synergistically interacting with one another arrange in a stable transition
      state, providing a low-energy pathway for this unique transformation. 

PMID- 24038993
TI  - Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ
      26481585), by the Pediatric Preclinical Testing Program.
AB  - BACKGROUND: Quisinostat (JNJ-26481585) is a second-generation pyrimidyl
      hydroxamic acid histone deacetylase (HDAC) inhibitor with high cellular potency
      towards Class I and II HDACs. Quisinostat was selected for clinical development
      as it showed prolonged pharmacodynamic effects in vivo and demonstrated improved
      single agent antitumoral efficacy compared to other analogs. PROCEDURES:
      Quisinostat was tested against the PPTP in vitro panel at concentrations ranging
      from 1.0 nM to 10 MUM and was tested against the PPTP in vivo panels at a dose of
      5 mg/kg (solid tumors) or 2.5 mg/kg (ALL models) administered intraperitoneally
      daily * 21. RESULTS: In vitro quisinostat demonstrated potent cytotoxic activity,
      with T/C% values approaching 0% for all of the cell lines at the highest
      concentration tested. The median relative IC50 value for the PPTP cell lines was
      2.2 nM (range <1-19 nM). quisinostat induced significant differences in EFS
      distribution compared to control in 21 of 33 (64%) of the evaluable solid tumor
      xenografts and in 4 of 8 (50%) of the evaluable ALL xenografts. An objective
      response was observed in 1 of 33 solid tumor xenografts while for the ALL panel,
      two xenografts achieved complete response (CR) or maintained CR, and a third ALL
      xenograft achieved stable disease. CONCLUSIONS: Quisinostat demonstrated broad
      activity in vitro, and retarded growth in the majority of solid tumor xenografts
      studied. The most consistent in vivo activity signals observed were for the
      glioblastoma xenografts and T-cell ALL xenografts.

PMID- 24038996
TI  - The Sox17CreERT2 knock-in mouse line displays spatiotemporal activation of Cre
      recombinase in distinct Sox17 lineage progenitors.
AB  - The HMG-box transcription factor Sox17 is essential for endoderm formation,
      vascular development, and definitive hematopoiesis. To investigate the fate of
      distinct Sox17-expressing progenitor cells in a spatiotemporal manner, we
      generated a hormone-inducible CreERT2 knock-in mouse line. By homologous
      recombination we fused a codon improved, ligand-dependent estrogen receptor Cre
      recombinase by an intervening viral T2A sequence for co-translational cleavage to
      the 3' coding region of Sox17. Induction of Cre activity by administration of
      tamoxifen at defined time points of early mouse development and subsequent
      genetic lineage tracing confirmed the inducibility and tissue specificity of Cre
      recombination. Furthermore, Cre activity could be selectively induced in extra
      embryonic and embryonic endoderm lineages, the primitive gut tube, and in
      endothelial cells of the vascular system as well as in the hemogenic endothelium
      of the dorsal aorta. The Sox17CreERT2 mouse line therefore represents a new tool
      for genetic lineage tracing in a tissue-specific manner and in addition enables
      lineage-restricted functional analysis.

PMID- 24038997
TI  - Phosphine-triggered co-catenation of :BR and CO on an iron atom.
AB  - The chain gang: By treatment of an iron bis(borylene) complex with PCy3 and
      subsequent stepwise substitution of a CO ligand by PMe3 , a catenated 1D OC-B-B
      CO chain was generated in the coordination sphere of iron. This is an CO analogue
      of the recently reported 1D B-B-B-B chain in the iron tetraboron complex
      [(OC)2Fe{BN(SiMe3)2}2(BDur)2]. Dur=2,3,5,6-tetramethylphenyl.

PMID- 24038998
TI  - The catalytically active copper-amyloid-Beta state: coordination site responsible
      for reactive oxygen species production.
AB  - Copper-amyloid-beta ROS production: Copper ions (red sphere, see picture) have
      been found to accumulate in amyloid-beta plaques and play a role in the
      generation of reactive oxygen species (ROS) within this context. Mass
      spectrometry studies were able to detail the sites of oxidation damage and shed
      new light on the mechanism of ROS production, important for the understanding of
      the pathogenicity of amyloid-beta peptides. 

PMID- 24038999
TI  - Cognitive and behavioral correlates of caudate subregion shape variation in
      fragile X syndrome.
AB  - Individuals with fragile X syndrome (FXS) exhibit frontal lobe-associated
      cognitive and behavioral deficits, including impaired general cognitive
      abilities, perseverative behaviors, and social difficulties. Neural signals
      related to these functions are communicated through frontostriatal circuits,
      which connect with distinct regions of the caudate nucleus (CN). Enlargement of
      the CN is the most robust and reproduced neuroanatomical abnormality in FXS, but
      very little is known on how this affects behavioral/cognitive outcomes in this
      condition. Here, we investigated topography within focal regions of the CN
      associated with prefrontal circuitry and its link with aberrant behavior and
      intellect in FXS. Imaging data were acquired from 48 individuals with FXS, 28 IQ
      matched controls without FXS (IQ-CTL), and 36 typically developing controls (TD
      CTL). Of the total participant count, cognitive and behavioral assessment data
      were obtained from 44 individuals with FXS and 27 participants in the IQ-CTL
      group. CN volume and topography were compared between groups. Correlations were
      performed between CN topography and cognitive as well as behavioral measures
      within FXS and IQ-CTL groups. As expected, the FXS group had larger CN compared
      with both IQ-CTL and TD-CTL groups. Correlations between focal CN topography and
      frontal lobe-associated cognitive and behavioral deficits in the FXS group
      supported the hypothesis that CN enlargement is related to abnormal orbitofrontal
      caudate and dorsolateral-caudate circuitry in FXS. These findings deepen our
      understanding of neuroanatomical mechanisms underlying cognitive-behavioral
      problems in FXS and hold promise for informing future behavioral and
      psychopharmacological interventions targeting specific neural pathways.

PMID- 24039000
TI  - Vegetation controls on northern high latitude snow-albedo feedback: observations
      and CMIP5 model simulations.
AB  - The snow-masking effect of vegetation exerts strong control on albedo in northern
      high latitude ecosystems. Large-scale changes in the distribution and stature of
      vegetation in this region will thus have important feedbacks to climate. The snow
      albedo feedback is controlled largely by the contrast between snow-covered and
      snow-free albedo (Deltaalpha), which influences predictions of future warming in
      coupled climate models, despite being poorly constrained at seasonal and century
      time scales. Here, we compare satellite observations and coupled climate model
      representations of albedo and tree cover for the boreal and Arctic region. Our
      analyses reveal consistent declines in albedo with increasing tree cover,
      occurring south of latitudinal tree line, that are poorly represented in coupled
      climate models. Observed relationships between albedo and tree cover differ
      substantially between snow-covered and snow-free periods, and among plant
      functional type. Tree cover in models varies widely but surprisingly does not
      correlate well with model albedo. Furthermore, our results demonstrate a
      relationship between tree cover and snow-albedo feedback that may be used to
      accurately constrain high latitude albedo feedbacks in coupled climate models
      under current and future vegetation distributions. 

PMID- 24039001
TI  - Hippocampal shape is predictive for the development of dementia in a normal,
      elderly population.
AB  - Previous studies have shown that hippocampal volume is an early marker for
      dementia. We investigated whether hippocampal shape characteristics extracted
      from MRI scans are predictive for the development of dementia during follow up in
      subjects who were nondemented at baseline. Furthermore, we assessed whether
      hippocampal shape provides additional predictive value independent of hippocampal
      volume. Five hundred eleven brain MRI scans from elderly nondemented participants
      of a prospective population-based imaging study were used. During the 10-year
      follow-up period, 52 of these subjects developed dementia. For training and
      evaluation independent of age and gender, a subset of 50 cases and 150 matched
      controls was selected. The hippocampus was segmented using an automated method.
      From the segmentation, the volume was determined and a statistical shape model
      was constructed. We trained a classifier to distinguish between subjects who
      developed dementia and subjects who stayed cognitively healthy. For all subjects
      the a posteriori probability to develop dementia was estimated using the
      classifier in a cross-validation experiment. The area under the ROC curve for
      volume, shape, and the combination of both were, respectively, 0.724, 0.743, and
      0.766. A logistic regression model showed that adding shape to a model using
      volume corrected for age and gender increased the global model-fit significantly
      (P = 0.0063). We conclude that hippocampal shape derived from MRI scans is
      predictive for dementia before clinical symptoms arise, independent of age and
      gender. Furthermore, the results suggest that hippocampal shape provides
      additional predictive value over hippocampal volume and that combining shape and
      volume leads to better prediction.

PMID- 24039002
TI  - Investigation of the competition between cell/surface and cell/cell interactions
      during neuronal cell culture on a micro-engineered surface.
AB  - To investigate the respective roles of topography and cell/cell interactions in
      the development of a guided neuronal network on an engineered surface,
      micropatterned PDMS substrates were generated with different microgrooves
      geometry and investigated for the influence of cell density on neurite outgrowth
      and alignment. Through this systematic investigation, using a human neuronal stem
      cell line, the rules of neuronal network development and guiding could be
      learned. The results show that when cell density is increased the influence on
      neuritic outgrowth and alignment is very different for the various grooves
      geometries. The data emphasized the competition, in neurite development, between
      physical cues brought by surface topographical features and cell to cell
      communications. These results can be of particular interest for designing
      functional neuronal networks with a controlled architecture. 

PMID- 24039003
TI  - Spectrofluorimetric determination of aluminum ions via complexation with luteolin
      in absolute ethanol.
AB  - An optimized and validated spectrofluorimetric method has been developed for the
      rapid determination of aluminum in absolute ethanol. The method is based on the
      chelation of aluminum and luteolin which results in a complex exhibiting an
      intense emission signal. The characterization of Al-luteolin complex was studied
      using ultraviolet-visible spectrometry, infrared spectrometry, fluorescence and
      mass spectrometry. The complex stoichiometry ratio of aluminum:luteolin was 1:2.
      The fluorescence of the complex was monitored at an emission wavelength of 545 nm
      with excitation at 518 nm. The linear concentration range was 6.5 * 10(-7) to 4.0
      * 10(-5)  M with a correlation coefficient of r = 0.998. The detection limit was
      5.0 * 10(-7)  M. The method was appropriately validated and yielded relative
      standard deviations of < 2.3% (n = 5), which was considered acceptable. The
      method was successfully applied in the determination of aluminum in river water,
      skin care products and pharmaceutical samples.

PMID- 24039004
TI  - Use of coated silver nanoparticles to understand the relationship of particle
      dissolution and bioavailability to cell and lung toxicological potential.
AB  - Since more than 30% of consumer products that include engineered nanomaterials
      contain nano-Ag, the safety of this material is of considerable public concern.
      In this study, Ag nanoparticles (NPs) are used to demonstrate that 20 nm
      polyvinylpyrrolidone (PVP or P) and citrate (C)-coated Ag NPs induce more
      cellular toxicity and oxidative stress than larger (110 nm) particles due to a
      higher rate of dissolution and Ag bioavailability. Moreover, there is also a
      higher propensity for citrate 20 nm (C20) nanoparticles to generate acute
      neutrophilic inflammation in the lung and to produce chemokines compared to C110.
      P110 has less cytotoxic effects than C110, likely due to the ability of PVP to
      complex released Ag(+) . In contrast to the more intense acute pulmonary effects
      of C20, C110 induces mild pulmonary fibrosis at day 21, likely as a result of
      slow but persistent Ag(+) release leading to a sub-chronic injury response.
      Interestingly, the released metallic Ag is incorporated into the collagen fibers
      depositing around airways and the lung interstitium. Taken together, these
      results demonstrate that size and surface coating affect the cellular toxicity of
      Ag NPs as well as their acute versus sub-chronic lung injury potential. 

PMID- 24039006
TI  - Severe intellectual disability, West syndrome, Dandy-Walker malformation, and
      syndactyly in a patient with partial tetrasomy 17q25.3.
AB  - We report on a de novo 0.5 Mb triplication (partial tetrasomy) of chromosome
      17q25.3 in a 10-year-old girl with severe intellectual disability, infantile
      seizures (West syndrome), moderate hearing loss, Dandy-Walker malformation,
      microcephaly, craniofacial dysmorphism, striking cutaneous syndactyly (hands 3-4,
      feet 2-3), joint laxity, and short stature. The triplication resulted from the
      unusual combination of a terminal duplication at 17qter and a cryptic
      translocation of an extra copy of the same segment onto chromosome 10qter. The
      breakpoint at 17q25.3 was located within the FOXK2 gene. SNP chip analysis
      suggested that the rearrangement occurred during paternal meiosis involving both
      paternal chromosomes 17.

PMID- 24039007
TI  - Synthesis of peripherally nitrated, aminated, and arylaminated subporphyrins.
AB  - 2-Nitro-5,10,15-tri(4-tert-butylphenyl)subporphyrin 2 was prepared by the
      nitration of 5,10,15-tri(4-tert- butylphenyl)subporphyrin 1a with five
      equivalents of Cu(NO3)2.5H2O in a mixed EtOAc/Ac2O solution and was reduced into
      2-amino-5,10,15-tri(4-tert-butylphenyl)subporphyrin 3. Bromination of 5,10,15
      triphenylsubporphyrin 1b with 1.5 equivalents of N-bromosuccinimide (NBS) gave 2
      bromo-5,10,15-triphenylsubporphyrin, which was converted into various 2-arylamino
      5,10,15-triphenylsubporphyrins (4a-4d) and 2-benzamido-5,10,15
      triphenylsubporphyrin 5 through Pd-catalyzed cross-coupling reactions. These
      molecules constitute the first examples of mono-beta-substituted subporphyrins.
      These subporphyrins exhibit significantly perturbed optical and electrochemical
      properties, which reflect a large influence of the peripherally attached
      substituents on the electronic networks of subporphyrins.

PMID- 24039005
TI  - Adipocyte reporter assays: application for identification of anti-inflammatory
      and antioxidant properties of mangosteen xanthones.
AB  - SCOPE: Three fluorescence biosensors were developed based on a 3T3-L1
      preadipocyte line that stably expressed Nfkb-RE/GFP, Fabp4-P/CFP, and Nrf2-P/YFP
      fluorescent reporters. We hypothesized that nutraceuticals' inflammatory,
      adipogenic, and antioxidant status will be identified based on the change in
      fluorescence in reporter adipocytes. We validated these assays with activators of
      NFkappaB, FABP4-regulating peroxisome proliferator activated receptor gamma, NFR2
      and, thereafter, tested known and unknown properties of mangostines (MGs), the
      xanthone metabolites in mangosteen fruit. METHODS AND RESULTS: We validated
      inflammatory and adipogenic properties of alpha-MG using an Nfkb-RE/GFP biosensor
      assay. Next, we identified unique properties of gamma-MG, a minor MG xanthone.
      gamma-MG suppressed adipogenesis and expression of adiponectin, but inhibited the
      Nfkb-RE/GFP reporter and secretion of inflammatory monocyte chemotactic protein 1
      as compared to the control adipocytes. We found that the inhibition of
      adipogenesis and Nfkb-mediated inflammation depends on a dose-dependent reduction
      of Nrf2 promoter activity by alpha-MG. The Nrf2 inhibition resulted in the
      reduced Pparg expression. alpha-MG did not directly influence Pparg activity in
      Fabp4-P/CFP adipocytes. CONCLUSION: alpha-MG-mediated antioxidant response via
      Nrf2 is a mechanism preventing adipogenesis and inflammation in adipocytes.
      Combined application of high-throughput biosensors could provide an effective
      platform for the identification of nutraceuticals and the mechanism of their
      actions in adipocytes and, potentially, in obese patients.

PMID- 24039008
TI  - The in-line measurement of plant cell biomass using radio frequency impedance
      spectroscopy as a component of process analytical technology.
AB  - Radio frequency impedance spectroscopy (RFIS) is a robust method for the
      determination of cell biomass during fermentation. RFIS allows non-invasive in
      line monitoring of the passive electrical properties of cells in suspension and
      can distinguish between living and dead cells based on their distinct behavior in
      an applied radio frequency field. We used continuous in situ RFIS to monitor
      batch-cultivated plant suspension cell cultures in stirred-tank bioreactors and
      compared the in-line data to conventional off-line measurements. RFIS-based
      analysis was more rapid and more accurate than conventional biomass
      determination, and was sensitive to changes in cell viability. The higher
      resolution of the in-line measurement revealed subtle changes in cell growth
      which were not accessible using conventional methods. Thus, RFIS is well suited
      for correlating such changes with intracellular states and product accumulation,
      providing unique opportunities for employing systems biotechnology and process
      analytical technology approaches to increase product yield and quality. 

PMID- 24039009
TI  - Progress in carbonylative [2+2+1] cycloaddition: utilization of a nitrile group
      as the pi component.
AB  - New tricks, old reactions: The treatment of 2-(1,2-propadienyl)phenylacetonitrile
      derivatives with a catalytic amount of [{RhCl(CO)dppp}2 ] (dppp=1,3
      bis(diphenylphosphanyl)propane) under a CO atmosphere produced benzo[f]oxyindole
      derivatives. This aza-Pauson-Khand-type reaction was applicable to aliphatic
      substrates, thus resulting in the formation of the azabicyclo[3.3.0]octadienone
      derivatives. 

PMID- 24039010
TI  - Wide electrochemical window of supercapacitors from coffee bean-derived
      phosphorus-rich carbons.
AB  - Phosphorus-rich carbons (PCs) were prepared by phosphoric acid activation of
      waste coffee grounds in different impregnation ratios. PCs were characterized by
      nitrogen and carbon dioxide adsorption and X-ray photoelectron spectroscopy. The
      results indicate that the activation step not only creates a porous structure,
      but also introduces various phosphorus and oxygen functional groups to the
      surface of carbons. As evidenced by cyclic voltammetry, galvanostatic
      charge/discharge, and wide potential window tests, a supercapacitor constructed
      from PC-2 (impregnation ratio of 2), with the highest phosphorus content, can
      operate very stably in 1 M H2 SO4 at 1.5 V with only 18 % degradation after 10
      000 cycles at a current density of 5 A g(-1) . Due to the wide electrochemical
      window, a supercapacitor assembled with PC-2 has a high energy density of 15 Wh
      kg(-1) at a power density of 75 W kg(-1) . The possibility of widening the
      potential window above the theoretical potential for the decomposition of water
      is attributed to reversible electrochemical hydrogen storage in narrow micropores
      and the positive effect of phosphorus-rich functional groups, particularly the
      polyphosphates on the carbon surface. 

PMID- 24039011
TI  - CD200 has an important role in the differential diagnosis of mature B-cell
      neoplasms by multiparameter flow cytometry.
AB  - Background: Multiparameter flow cytometry is a useful tool for the diagnostic
      evaluation of mature B-cell neoplasms (MBN). Recently, it has been shown that
      CD200 may improve the distinction between chronic lymphocytic leukemia (CLL;
      CD200+) and mantle cell lymphoma (MCL; CD200-), but the role of CD200 expression
      in atypical CLL and other MBN remains to be established. Methods: To address this
      issue, we investigated the expression of CD200 in 159 consecutive cases of MBN.
      Results: CD200 was strongly expressed in CLL and was revealed to be an excellent
      marker to distinguish CLL from MCL, even in cases of atypical CLL. However, lack
      of CD200 was not an exclusive finding of MCL, being also observed in other MBNs.
      Furthermore, CD200 was highly expressed in hairy cell leukemia, being useful in
      the differential diagnosis of lymphomas with villous lymphocytes. Herein, we
      propose an algorithm to classify CD5+ MBNs based on the expression of CD200,
      CD11c, heavy chain immunoglobulins and Matutes score. Conclusions: These results
      expand the understanding of the CD200 expression in MBNs, giving further support
      for the inclusion of this marker in the routine investigation by flow cytometry.
      (c) 2013 Clinical Cytometry Society.

PMID- 24039012
TI  - Dispersion-driven conformational isomerism in sigma-bonded dimers of larger
      acenes.

PMID- 24039013
TI  - Children <1 year show an inferior outcome when treated according to the
      traditional LGG treatment strategy: a report from the German multicenter trial
      HIT-LGG 1996 for children with low grade glioma (LGG).
AB  - BACKGROUND: Children diagnosed with LGG at an age <1 year are reported to have an
      impaired prognosis in comparison to older patients. Analysis of this subgroup
      could reveal the necessity to develop risk-adapted treatment approaches.
      PROCEDURE: Children <1 year at diagnosis (n = 66, median age 7.3 months, 33
      female, none NFI) from the HIT-LGG 1996 cohort were analyzed for risk factors for
      EFS, PFS and OS. Several children suffered from diencephalic syndrome (DS, n =
      22) and primary dissemination (DLGG, n = 9), 50 had a supratentorial midline
      (SML) location. Extent of resection was complete/subtotal in 12, partial in 15,
      biopsy in 27. Tumors were pilocytic astrocytoma WHO grade I (n = 33), other WHO
      grade I (n = 14), pilomyxoid astrocytomas WHO grade II (n = 3), and
      neuroepithelial tumors WHO grade II (n = 4). RESULTS: One-year EFS was 34.8%. SML
      localisation, minor extent of surgery, pilocytic astrocytoma, DLGG and DS were
      unfavorable predictive factors. No additional non-surgical therapy was applied in
      24, 36 were treated with VCR/carboplatin chemotherapy, 6 with radiotherapy (5/6
      brachytherapy). Ten-year-PFS-rate following non-surgical therapy was 16.7%; DS
      and DLGG were unfavorable factors. Ten-year-OS-rate was 72.8%, lower for children
      <6 months at diagnosis, with DS, or with DLGG. At last follow up in August 2011,
      vision in 31 living children was often severely impaired. CONCLUSIONS: Children
      <1 year at diagnosis have a conspicuously impaired survival with current
      treatment approaches. Age <6 months, diencephalic syndrome and dissemination
      constitute risk factors for even lower PFS and OS. Treatment adaptations are
      needed to improve outcome and molecular genetics may explain tumor
      aggressiveness.

PMID- 24039014
TI  - Nanostructures of nematic materials of laterally branched molecules.
AB  - The synthesis and small-angle X-ray scattering (SAXS) characterization is
      reported for 20 laterally branched mesogenic molecules, which are derived from
      the common rod-shaped 2,5-bis([4-(octyloxy)phenyl]carbonyloxy) benzoic acid unit.
      These compounds have a varying degree of flexibility, in that their lateral
      branch is formed upon conversion of the acid to either an ester or an amide, and
      most laterally branched molecules exhibit relatively wide nematic liquid-crystal
      phases with a direct nematic-to-crystal transition at lower temperatures. SAXS
      studies reveal the presence of smectic-like nanostructures (clusters) with short
      range order in the nematic phase, with characteristic correlation lengths from 3
      to over 10 nm. The smectic layers that are contained in these clusters are tilted
      with respect to the nematic director by angles ranging from 0 degrees  (i.e.
      untilted) to 55 degrees . In some compounds, the intensity of the SAXS peak
      corresponding to the smectic layer spacing depends strongly on temperature. The
      main features of the nanostructures can be understood based on the molecular
      structure; therefore, guiding future synthetic work towards more precisely
      controlled and technologically useful nanostructures in nematics. 

PMID- 24039015
TI  - Musculoskeletal pain and physical functioning in the oldest old.
AB  - BACKGROUND: Little is known about the impact of pain on physical functioning
      among the oldest-old subjects. In this study, we first examined the associations
      between the number of painful sites and measures of physical functioning
      reflecting different stages of the disablement process (physical impairment,
      functional limitation and disability) among nonagenarians (more than ninety years
      old persons). Second, we described the effect of painful sites on disability
      during a 2-year follow-up period. METHODS: This study is based on baseline (n =
      1177) and 2-year follow-up (n = 709) data of the nationwide Danish 1905 cohort
      study. Musculoskeletal pain was assessed as reported pain in back, hips or knees
      when moving or resting. Physical performance measures included maximum grip
      strength and habitual walking speed. Disability in performing activities of daily
      living was defined as the need for assistive device or personal help in
      transferring, dressing, washing, using toilet and/or walking indoors. RESULTS: At
      baseline, the number of painful sites was significantly associated with measured
      grip strength and walking speed as well as self-reported disability in a stepwise
      manner; the more sites with pain, the poorer the physical functioning. The follow
      up analyses showed corresponding but slightly weaker stepwise associations
      between baseline pain and disability level at follow-up, and indicated that
      although on the whole, single or multi-site pain did not predict the onset of
      disability, multi-site pain increased the risk of developing severe disability.
      CONCLUSIONS: The findings of this study suggest that musculoskeletal pain in
      nonagenarians is highly prevalent and is associated with poor physical
      performance and disability.

PMID- 24039016
TI  - Activity interventions for cognitive problems.
AB  - Cancer and its life-saving treatments often result in long-term impairments in
      neurocognitive functions. These neurocognitive impairments are not only
      problematic, but they also limit the ability to perform meaningful everyday
      activities critical to independence in the home, school, and community. The
      "bottom-up" and "top-down" models inherent in many neurological rehabilitation
      interventions provide a gross framework for describing interventions designed to
      address neurocognitive functions. Activity interventions show promise for
      improving performance of everyday activities, as well as improving underlying
      neurocognitive functions. However, additional empirical examination is warranted.
      Future studies examining activity interventions should clearly specify the active
      ingredient of the intervention, and evaluate the impact of the intervention on
      neurocognitive as well as activity-based outcomes.

PMID- 24039017
TI  - Peptide-catalyzed regio- and enantioselective reduction of alpha,beta,gamma,delta
      unsaturated aldehydes.
AB  - A resin-supported peptide catalyst (see box in the scheme) was used in the title
      reaction. The inherent regioselectivity was overcome by the peptide catalyst to
      promote the 1,6-selective reaction prior to 1,4-reduction. High stereoconvergence
      was also achieved when using a mixture of geometric isomers of the starting
      aldehydes. Ach=1-amino-1-cyclohexanecarboxylic acid. 

PMID- 24039018
TI  - Dynamic nuclear polarization NMR spectroscopy: revealing multiple conformations
      in lipid-anchored peptide vaccines.

PMID- 24039019
TI  - A controllable gate effect in cobalt(II) organic frameworks by reversible
      structure transformations.
AB  - With H2 O or NH3 stimuli, the blue cobalt-based metal-organic framework (MOF) BP
      can reversibly transform to red RP. The removal/recovery of terephthalate ligands
      accompanied by the transformation leads to a gate effect, which allows the
      encapsulation and release of small solvent molecules under certain conditions.
      This is the first example of topology transformation from a self-penetrating to
      interpenetrating net in 3D MOFs. 

PMID- 24039020
TI  - Multidimensional separation of tryptic peptides from human serum proteins using
      reversed-phase, strong cation exchange, weak anion exchange, and fused-core
      fluorinated stationary phases.
AB  - Proteome profiling of crude serum is a challenging task due to the wide dynamic
      range of protein concentrations and the presence of high-abundance proteins,
      which cover >90% of the total protein mass in serum. Peptide fractionation on
      strong cation exchange, weak anion exchange in the electrostatic repulsion
      hydrophilic interaction chromatography (ERLIC) mode, RP C18 at pH 2.5 (low pH),
      fused-core fluorinated at pH 2.5, and RP C18 at pH 9.7 (high pH) stationary
      phases resulted in two to three times more identified proteins and three to four
      times more identified peptides in comparison with 1D nanoChip-LC-MS/MS quadrupole
      TOF analysis (45 proteins, 185 peptides). The largest number of peptides and
      proteins was identified after prefractionation in the ERLIC mode due to the more
      uniform distribution of peptides among the collected fractions and on the RP
      column at high pH due to the high efficiency of RP separations and the
      complementary selectivity of both techniques to low-pH RP chromatography. A 3D
      separation scheme combining ERLIC, high-pH RP, and low-pH nanoChip-LC-MS/MS for
      crude serum proteome profiling resulted in the identification of 208 proteins and
      1088 peptides with the lowest reported concentration of 11 ng/mL for heat shock
      protein 74. 

PMID- 24039021
TI  - Deep breathing heart rate variability is associated with inspiratory muscle
      weakness in chronic heart failure.
AB  - BACKGROUND AND PURPOSE: There is a synchronism between the respiratory and
      cardiac cycles. However, the relationship of inspiratory muscle weakness in
      chronic heart failure (CHF) on cardiac autonomic modulation is unknown. The
      purpose of the present investigation was to evaluate the impact of inspiratory
      muscle strength on the magnitude of respiratory sinus arrhythmia. METHODS: Ten
      CHF (62 +/- 7 years--left ventricle eject fraction of 40 +/- 5% and New York
      Heart Association class I-III) and nine matched-age healthy volunteers (64 +/- 5
      years) participated in this study. Heart rate variability (HRV) was obtained at
      rest and during deep breathing manoeuvre (DB-M) by electrocardiograph. RESULTS:
      CHF patients demonstrated impaired cardiac autonomic modulation at rest and
      during DB-M when compared with healthy subjects (p < 0.05). Moreover, significant
      and positive correlations between maximal inspiratory pressure and inspiratory
      expiratory differences (r = 0.79), expiratory/inspiratory ratio (r = 0.83), root
      mean square of the successive differences (r = 0.77), standard deviation of NN
      intervals (r = 0.77), low frequency (r = 0.77), and high frequency (r = 0.70)
      were found during DB-M. At rest, significant correlations were found also.
      CONCLUSION: Patients with CHF presented impaired cardiac autonomic modulation at
      rest. In addition, cardiac autonomic control of heart rate was associated with
      inspiratory muscle weakness in CHF. Based on this evidence, recommendations for
      future research applications of respiratory muscle training can bring to light a
      potentially valuable target for rehabilitation.

PMID- 24039022
TI  - A comparative CEST NMR study of slow conformational dynamics of small GTPases
      complexed with GTP and GTP analogues.

PMID- 24039023
TI  - Increased cortical thickness in a frontoparietal network in social anxiety
      disorder.
AB  - Social anxiety disorder (SAD) is the second leading anxiety disorder. On the
      functional neurobiological level, specific brain regions involved in the
      processing of anxiety-laden stimuli and in emotion regulation have been shown to
      be hyperactive and hyper-responsive in SAD such as amygdala, insula and orbito-
      and prefrontal cortex. On the level of brain structure, prior studies on
      anatomical differences in SAD resulted in mixed and partially contradictory
      findings. Based on previous functional and anatomical models of SAD, this study
      examined cortical thickness in structural magnetic resonance imaging data of 46
      patients with SAD without comorbidities (except for depressed episode in one
      patient) compared with 46 matched healthy controls in a region of interest
      analysis and in whole-brain. In a theory-driven ROI-analysis, cortical thickness
      was increased in SAD in left insula, right anterior cingulate and right temporal
      pole. Furthermore, the whole-brain analysis revealed increased thickness in right
      dorsolateral prefrontal and right parietal cortex. This study detected no regions
      of decreased cortical thickness or brain volume in SAD. From the perspective of
      brain networks, these findings are in line with prior functional differences in
      salience networks and frontoparietal networks associated with executive
      controlling and attentional functions.

PMID- 24039024
TI  - Reduced grey matter perfusion without volume loss in early relapsing-remitting
      multiple sclerosis.
AB  - BACKGROUND: Grey matter (GM) pathology in multiple sclerosis (MS) is associated
      with progressive long-term disability. Detection of GM abnormalities in early MS
      may therefore be valuable in understanding and predicting the long-term course.
      However, structural MRI measures such as volume loss have shown only modest
      abnormalities in early relapsing-remitting MS (RRMS). We therefore investigated
      for evidence of abnormality in GM perfusion, consistent with metabolic
      dysfunction, in early RRMS. METHODS: 25 RRMS patients with <=5 years disease
      duration and 25 age-matched healthy controls underwent 3 Tesla MRI with a pseudo
      continuous arterial spin labelling sequence to quantify GM perfusion and a
      volumetric T1-weighted sequence to measure GM volume. Neurological status was
      assessed in patients and neuropsychological evaluation undertaken in all
      subjects. Voxel-based analysis was used to compare regional GM perfusion and
      volume measures in patients and controls. RESULTS: There was reduced global GM
      perfusion in patients versus controls (50.6+/-5.8 mL/100 g/min vs 54.4+/-7.6
      mL/100 g/min, p=0.04). Voxel-based analysis revealed extensive regions of
      decreased cortical and deep GM perfusion in MS subjects. Reduced perfusion was
      associated with impaired memory scores. There was no reduction in global or
      regional analysis of GM volume in patients versus controls. CONCLUSIONS: The
      decrease in GM perfusion in the absence of volume loss is consistent with
      neuronal metabolic dysfunction in early RRMS. Future studies in larger cohorts
      and longitudinal follow-up are needed to investigate the functional and
      prognostic significance of the early GM perfusion deficits observed.

PMID- 24039025
TI  - Predicting delirium after a stroke.

PMID- 24039026
TI  - Neuronal intranuclear inclusion disease cases with leukoencephalopathy diagnosed
      via skin biopsy.

PMID- 24039028
TI  - A structural MRI study of motor conversion disorder: evidence of reduction in
      thalamic volume.
AB  - OBJECTIVE: To investigate potential abnormalities in subcortical brain structures
      in conversion disorder (CD) compared with controls using a region of interest
      (ROI) approach. METHODS: Fourteen patients with motor CD were compared with 31
      healthy controls using high-resolution MRI scans with an ROI approach focusing on
      the basal ganglia, thalamus and amygdala. Brain volumes were measured using
      Freesurfer, a validated segmentation algorithm. RESULTS: Significantly smaller
      left thalamic volumes were found in patients compared with controls when
      corrected for intracranial volume. These reductions did not vary with handedness,
      laterality, duration or severity of symptoms. CONCLUSIONS: These differences may
      reflect a primary disease process in this area or be secondary effects of the
      disorder, for example, resulting from limb disuse. Larger, longitudinal
      structural imaging studies will be required to confirm the findings and explore
      whether they are primary or secondary to CD.

PMID- 24039027
TI  - Grammatical comprehension deficits in non-fluent/agrammatic primary progressive
      aphasia.
AB  - IMPORTANCE: Grammatical comprehension difficulty is an essential supporting
      feature of the non-fluent/agrammatic variant of primary progressive aphasia
      (naPPA), but well-controlled clinical measures of grammatical comprehension are
      unavailable. OBJECTIVE: To develop a measure of grammatical comprehension and
      examine this comparatively in PPA variants and behavioural-variant frontotemporal
      degeneration (bvFTD) and to assess the neuroanatomic basis for these deficits
      with volumetric grey matter atrophy and whole-brain fractional anisotropy (FA) in
      white matter tracts. DESIGN: Case-control study. SETTING: Academic medical
      centre. PARTICIPANTS: 39 patients with variants of PPA (naPPA=12, lvPPA=15 and
      svPPA=12), 27 bvFTD patients without aphasia and 12 healthy controls. MAIN
      OUTCOME MEASURE: Grammatical comprehension accuracy. RESULTS: Patients with naPPA
      had selective difficulty understanding cleft sentence structures, while all PPA
      variants and patients with bvFTD were impaired with sentences containing a centre
      embedded subordinate clause. Patients with bvFTD were also impaired understanding
      sentences involving short-term memory. Linear regressions related grammatical
      comprehension difficulty in naPPA to left anterior-superior temporal atrophy and
      reduced FA in corpus callosum and inferior frontal-occipital fasciculus.
      Difficulty with centre-embedded sentences in other PPA variants was related to
      other brain regions. CONCLUSIONS AND RELEVANCE: These findings emphasise a
      distinct grammatical comprehension deficit in naPPA and associate this with
      interruption of a frontal-temporal neural network.

PMID- 24039029
TI  - Libera nos a malo.

PMID- 24039030
TI  - Nondigestible oligosaccharides exert nonprebiotic effects on intestinal
      epithelial cells enhancing the immune response via activation of TLR4-NFkappaB.
AB  - SCOPE: Prebiotic effects of non absorbable glucids depend mainly on digestion by
      the colonic microbiota. Our aim was to assess nonprebiotic, direct effects of 4
      prebiotics, namely fructooligosaccharides, inulin, galactooligosaccharides, and
      goat's milk oligosaccharides on intestinal epithelial cells. METHODS AND RESULTS:
      Prebiotics were tested in intestinal epithelial cell 18 (IEC18), HT29, and Caco-2
      cells. Cytokine secretion was measured by ELISA and modulated with
      pharmacological probes and gene silencing. Prebiotics induced the production of
      growth-related oncogene, (GROalpha), monocyte chemoattractant protein 1 (MCP-1),
      and macrophage inflammatory protein 2 (MIP2) in IEC18 cells, with an efficacy
      that was 50-80% that of LPS. Prebiotics did not change RANTES expression, which
      was robustly induced by LPS in IEC18 cells. Cytokine secretion was suppressed by
      Bay11-7082, an inhibitor of IkappaB-alpha phosphorylation. The response was
      markedly decreased by Myd88 or TLR4 gene knockdown. Prebiotics also elicited
      cytokine production in HT29 but not in Caco-2 cells, consistent with reduced and
      vestigial expression of TLR4 in these cell lines, respectively. Prebiotic-induced
      MCP-1 secretion was reduced also in colonic explants from TLR4 KO mice compared
      with the controls. CONCLUSIONS: We conclude that prebiotics are TLR4 ligands in
      intestinal epithelial cells and that this may be a relevant mechanism for their
      in vivo effects.

PMID- 24039031
TI  - Microdeletions of 3p21.31 characterized by developmental delay, distinctive
      features, elevated serum creatine kinase levels, and white matter involvement.
AB  - Interstitial deletions of chromosome 3 are rare, and only one patient with a
      microdeletion of 3p21.31 has been reported to date. We identified two additional
      cases of patients with microdeletions of 3p21.31. The characteristic clinical
      features of developmental delay and distinctive facial features (including arched
      eyebrows, hypertelorism, epicanthus, and micrognathia) were seen both in the
      previously reported patient and in the two newly identified patients. In these
      two new cases, additional features, including elevated serum creatine kinase
      levels and characteristic neuroradiological features with white matter
      involvement, were seen. These features had not been described in the previous
      case in which the patient was examined during infancy, suggesting an age
      dependent mechanism. The shortest region of overlap among the three deletions
      narrowed down the candidate genes that may be responsible for the common
      neurological features to the bassoon (presynaptic cytomatrix protein) gene (BSN),
      which has an important function in neuronal synapses. In this study, we confirmed
      common phenotypic features in the patients with microdeletions of 3p21.31 and
      identified additional features that have not been reported previously. Because
      the constellation of such characteristic features is quite unique, clinical
      manifestations of the patients with microdeletions of 3p21.31 would be clinically
      recognizable as a contiguous gene deletion syndrome.

PMID- 24039032
TI  - Studies on the interaction between vincamine and human serum albumin: a
      spectroscopic approach.
AB  - The interaction between vincamine (VCM) and human serum albumin (HSA) has been
      studied using a fluorescence quenching technique in combination with UV/vis
      absorption spectroscopy, Fourier transform infrared (FT-IR) spectroscopy,
      circular dichroism (CD) spectroscopy and molecular modeling under conditions
      similar to human physiological conditions. VCM effectively quenched the intrinsic
      fluorescence of HSA via static quenching. The binding constants were calculated
      from the fluorescence data. Thermodynamic analysis by Van't Hoff equation
      revealed enthalpy change (DeltaH) and entropy change (DeltaS) were -4.57 kJ/mol
      and 76.26 J/mol/K, respectively, which indicated that the binding process was
      spontaneous and the hydrophobic interaction was the predominant force. The
      distance r between the donor (HSA) and acceptor (VCM) was obtained according to
      the Forster's theory of non-radiative energy transfer and found to be 4.41 nm.
      Metal ions, viz., Na(+), K(+), Li(+), Ni(2+), Ca(2+), Zn(2+) and Al(3+) were
      found to influence binding of the drug to protein. The 3D fluorescence, FT-IR and
      CD spectral results revealed changes in the secondary structure of the protein
      upon interaction with VCM. Furthermore, molecular modeling indicated that VCM
      could bind to the subdomain IIA (site I) of HSA.

PMID- 24039033
TI  - Brain network alterations in Alzheimer's disease measured by eigenvector
      centrality in fMRI are related to cognition and CSF biomarkers.
AB  - Recent imaging studies have demonstrated functional brain network changes in
      patients with Alzheimer's disease (AD). Eigenvector centrality (EC) is a graph
      analytical measure that identifies prominent regions in the brain network
      hierarchy and detects localized differences between patient populations. This
      study used voxel-wise EC mapping (ECM) to analyze individual whole-brain resting
      state functional magnetic resonance imaging (MRI) scans in 39 AD patients (age 67
      +/- 8) and 43 healthy controls (age 69 +/- 7). Between-group differences were
      assessed by a permutation-based method. Associations of EC with biomarkers for AD
      pathology in cerebrospinal fluid (CSF) and Mini Mental State Examination (MMSE)
      scores were assessed using Spearman correlation analysis. Decreased EC was found
      bilaterally in the occipital cortex in AD patients compared to controls. Regions
      of increased EC were identified in the anterior cingulate and paracingulate
      gyrus. Across groups, frontal and occipital EC changes were associated with
      pathological concentrations of CSF biomarkers and with cognition. In controls,
      decreased EC values in the occipital regions were related to lower MMSE scores.
      Our main finding is that ECM, a hypothesis-free and computationally efficient
      analysis method of functional MRI (fMRI) data, identifies changes in brain
      network organization in AD patients that are related to cognition and underlying
      AD pathology. The relation between AD-like EC changes and cognitive performance
      suggests that resting-state fMRI measured EC is a potential marker of disease
      severity for AD.

PMID- 24039034
TI  - Porous hydrogels from shark skin collagen crosslinked under dense carbon dioxide
      atmosphere.
AB  - The possibility to fabricate marine collagen porous structures crosslinked with
      genipin under high pressure carbon dioxide is investigated. Collagen from shark
      skin is used to prepare pre-scaffolds by freeze-drying. The poor stability of the
      structures and low mechanical properties require crosslinking of the structures.
      Under dense CO2 atmosphere, crosslinking of collagen pre-scaffolds is allowed for
      16 h. Additionally, the hydrogels are foamed and the scaffolds obtained present a
      highly porous structure. In vitro cell culture tests performed with a chondrocyte
      like cell line show good cell adherence and proliferation, which is a strong
      indication of the potential of these scaffolds to be used in tissue cartilage
      tissue engineering. 

PMID- 24039035
TI  - Engineering the pH-responsive catalytic behavior of AuNPs by DNA.
AB  - Noble metal nanoparticles have attracted much interest in the heterogeneous
      catalysis. Particularly, efficient manipulation of the responsive catalytic
      properties of the metal nanoparticles is an interesting topic. In this work, a
      simple and efficient strategy is developed to regulate the pH-responsive
      catalytic activities of glucose oxidase (GOx)-mimicking gold nanoparticles
      (AuNPs). Four DNA strands (regulating strands) that differ slightly in sequences
      are used to interact non-covalently with citrate-capped AuNPs, resulting in
      markedly distinct pH-dependent catalytic behavior of AuNPs. This is ascribed to
      the characteristic pH-induced conformational change of the DNA strands that leads
      to the different adsorption capability to the NPs surface, as demonstrated by pH
      CD profiles of the respective DNA molecules. The pH-dependent catalysis of AuNPs
      is also encoded with structural information of the double-stranded DNA (including
      regulating strands and their complementary strands) that has conformation
      resistant or responsive to pH change. As a result, the catalysis can be
      programmed into an AND gate, a XNOR gate or a NOT gate, using pH and
      complementary strand as the inputs, the nanoparticle activity as the output and
      the regulating strands as the programs. This work can be expanded by engineering
      the catalytic behavior of noble metal nanoparticles to respond smartly to a
      variety of environmental stimuli, such as metal ions or light wavelengths. These
      results may provide insight into understanding ligand-regulated nanometallic
      catalysis. 

PMID- 24039036
TI  - Nanoscale investigation of the degradation mechanism of a historical chrome
      yellow paint by quantitative electron energy loss spectroscopy mapping of
      chromium species.
AB  - Getting the picture: The investigation of 100 year old chrome yellow paint by
      transmission electron microscopy and spectroscopy has led to the identification
      of four types of core-shell particles. This nanoscale investigation has allowed a
      mechanism to be proposed for the darkening of some bright yellow colors in Van
      Gogh's paintings (e.g. in Falling leaves (Les Alyscamps), 1888). 

PMID- 24039037
TI  - Stabilization of the triphosphallyl ligand eta3-P3{P(O)H} at iridium via alkaline
      activation of P4.
AB  - The selective functionalization of the polyphosphorus moiety Ph2PCH2PPh2PPPP
      present as a tetrahapto-ligand in complex [Ir(dppm)(Ph2PCH2PPh2PPPP)](+) (1,
      dppm=Ph2PCH2PPh2) was obtained by reaction of 1 with water under basic conditions
      at room temperature. The formation of the new triphosphaallyl moiety eta(3)
      P3{P(O)H} was determined in solution by NMR spectroscopy, and confirmed in the
      solid state by a single-crystal X-ray structure of the stable product
      [Ir(kappa(2)-dppm)(kappa(1)-dppm)(eta(3)-P3{P(O)H})] (2). In solution, 2 has a
      fluxional behavior attributable to the four P atoms belonging to the
      tetraphosphorus moiety in 1 and exhibits a chemical exchange process involving
      the two PPh2 moieties of the same bidentate ligand, as determined by 1D and 2D
      NMR spectroscopy experiments carried out at variable temperature. The mechanism
      of the reaction was investigated at the DFT level, which suggested a selective
      attack of an in-situ generated OH(-) anion on one of the non-coordinated
      phosphorus atoms of the P4 moiety. The reaction then evolves through an acid
      assisted tautomerization, which leads to the final compound 2. Bonding analysis
      pointed out that the new unsubstituted P3-unit in the eta(3)-P3{P(O)H} moiety
      behaves as a triphosphallyl ligand.

PMID- 24039038
TI  - Site-specific carbon deposition for hierarchically ordered core/shell-structured
      graphitic carbon with remarkable electrochemical performance.
AB  - A fascinating core-shell-structured graphitic carbon material composed of ordered
      microporous core and uniform mesoporous shell is fabricated for the first time
      through a site-specific chemical vapor deposition process by using a
      nanozeolite@mesostructured silica composite molecular sieve as the template. The
      mesostructure-directing agent cetyltrimethylammonium bromide in the shell of the
      template can be either burned off or carbonized so that it is successfully
      utilized as a pore switch to turn the shell of the template "on" or "off" to
      allow selective carbon deposition. The preferred carbon deposition process can be
      performed only in the inner microporous zeolite cores or just within the outer
      mesoporous shells, resulting in a zeolite-like ordered microporous carbon or a
      hollow mesoporous carbon. Full carbon deposition in the template leads to the new
      core-shell-structured microporous@mesoporous carbon with a nanographene
      constructed framework for fast electron transport, a microporous nanocore with
      large surface area for high-capacity storage of lithium ions, a mesoporous shell
      with highly opened mesopores as a transport layer for lithium ions and electron
      channels to access inner cores. The ordered micropores are protected by the
      mesoporous shell, avoiding pore blockage as the formation of solid electrolyte
      interphase layers. Such a unique core-shell-structured microporous@mesoporous
      carbon material represents a newly established lithium ion storage model,
      demonstrating high reversible energy storage, excellent rate capability, and long
      cyclic stability. 

PMID- 24039039
TI  - Gold-catalyzed oxidative rearrangement involving 1,2-acyl migration: efficient
      synthesis of functionalized dihydro-gamma-carbolines from alpha-(2-indolyl)
      propargylic alcohols and imines.

PMID- 24039040
TI  - Peripheral blood lymphocyte recovery and overall survival in pediatric acute
      lymphoblastic leukemia.

PMID- 24039041
TI  - Complementarity of evaluation of myeloperoxidase expression by flow cytometry and
      immunohistochemistry on bone marrow trephine biopsy sections in acute myeloid
      leukaemia.

PMID- 24039042
TI  - Formation mechanism of a silane-PVA/PVAc complex film on a glass fiber surface.
AB  - Mechanical properties of glass fiber reinforced composite materials are affected
      by fiber sizing. A complex film formation, based on a silane film and PVA/PVAc
      (polyvinyl alcohol/polyvinyl acetate) microspheres on a glass fiber surface is
      determined at 1) the nanoscale by using atomic force microscopy (AFM), and 2) the
      macroscale by using the zeta potential. Silane groups strongly bind through the
      Si-O-Si bond to the glass surface, which provides the attachment mechanism as a
      coupling agent. The silane groups form islands, a homogeneous film, as well as
      empty sites. The average roughness of the silanized surface is 6.5 nm, whereas it
      is only 0.6 nm for the non-silanized surface. The silane film vertically
      penetrates in a honeycomb fashion from the glass surface through the deposited
      PVA/PVAc microspheres to form a hexagonal close pack structure. The silane film
      not only penetrates, but also deforms the PVA/PVAc microspheres from the
      spherical shape in a dispersion to a ellipsoidal shape on the surface with
      average dimensions of 300/600 nm. The surface area value Sa represents an area of
      PVA/PVAc microspheres that are not affected by the silane penetration. The areas
      are found to be 0.2, 0.08, and 0.03 MUm(2) if the ellipsoid sizes are 320/570,
      300/610, and 270/620 nm for silane concentrations of 0, 3.8, and 7.2 MUg mL(-1),
      respectively. The silane film also moves PVA/PVAc microspheres in the process of
      complex film formation, from the low silane concentration areas to the complex
      film area providing enough silane groups to stabilize the structure. The values
      for the residual silane honeycomb structure heights (Ha ) are 6.5, 7, and 12 nm
      for silane concentrations of 3.8, 7.2, and 14.3 MUg mL(-1), respectively. The pH
      dependent zeta-potential results suggest a specific role of the silane groups
      with effects on the glass fiber surface and also on the PVA/PVAc microspheres.
      The non-silanized glass fiber surface and the silane film have similar zeta
      potentials ranging from -64 to -12 mV at pH's of 10.5 and 3, respectively. The
      zeta potentials for the PVA/PVAc microspheres on the glass fiber surface and
      within the silane film significantly decrease and range from -25 to -5 mV. The
      shapes of the pH-dependent zeta potentials are different in the cases of silane
      groups over a pH range from 7 to 4. A triple-layer model is used to fit the non
      silanized glass surface and the silane film. The value of the surface-site
      density for Gamma(Xglass) and Gamma(Xsilane), in which X denotes the Al-O-Si
      group, differs by a factor of 10(-4), which suggests an effective coupling of the
      silane film. A soft-layer model is used to fit the silane-PVA/PVAc complex film,
      which is approximated as four layers. Such a simplification and compensation of
      the microsphere shape gives an approximation of the relevant widths of the layers
      as the follows: 1) the layer of the silane groups makes up 10% of the total
      length (27 nm), 2) the layer of the first PVA shell contributes 30% to the total
      length (81 nm), 3) the layer of the PVAc core contributes 30% to the total length
      (81 nm), and finally 4) the layer of the second PVA shell provides 30% of the
      total length (81 nm). The coverage simulation resulted in a value of 0.4, which
      corresponds with the assumption of low-order coverage, and is supported by the
      AFM scans. Correlating the results of the AFM scans, and the zeta potentials
      sheds some light on the formation mechanism of the silane-PVA/PVAc complex film.

PMID- 24039043
TI  - Stabilization of peptides for intracellular applications by phosphoramidate
      linked polyethylene glycol chains.

PMID- 24039044
TI  - Comparative expression and regulation of TMSB4X in male reproductive tissues of
      rats and chickens.
AB  - Thymosin beta4 (TMSB4X) belongs to a class of highly conserved small proteins
      that are present in a high abundance in immune tissues, where it participates in
      various biological activities, including anti-inflammation, wound healing,
      apoptosis, and cell survival. However, little is known about the expression and
      regulation of TMSB4X in reproductive tissues. The aim of this study was to
      examine the expression of rat Tmsb4x and chicken TMSB4X genes during testicular
      and epididymal development. Rat Tmsb4x was strongly detected in the spermatogonia
      and spermatocytes of testis at early postnatal development and transmitted to
      Leydig cells at sexual maturation. Also, rat Tmsb4x was detected at an increased
      level in the epididymis during postnatal development. When compared to the rat,
      expression of the chicken TMSB4X gene was low in the testis and epididymal
      region, and the mRNA localization was also unexpected. Three experiments were
      performed to examine the regulation of rat Tmsb4x in the epididymis: after
      elimination of Leydig cells using ethylene dimethane sulfonate (EDS); after
      destruction of the testis by cryptorchidism; and after castration. EDS-treated
      and castrated rats were injected with testosterone propionate. The expression of
      Tmsb4x was significantly reduced in the epididymis of EDS-treated, and castrated
      rats. In contrast, Tmsb4x was significantly enhanced in the epididymis after
      testosterone treatment. The expression of rat Tmsb4x was also regulated in the
      epididymis after cryptorchidism. Collectively, the expression of Tmsb4x was
      strongly detected in the testis and epididymis of rats, and was highly regulated
      in the epididymis by testosterone.

PMID- 24039045
TI  - Effects of Ti, PMMA, UHMWPE, and Co-Cr wear particles on differentiation and
      functions of bone marrow stromal cells.
AB  - This study investigates the roles of orthopedic biomaterial particles [Ti-alloy,
      poly(methyl methacrylate) (PMMA), ultrahigh-molecular-weight polyethylene
      (UHMWPE), Co-Cr alloy] on the differentiation and functions of bone marrow
      stromal cells (BMSCs). Cells were isolated from femurs of BALB/c mice and
      cultured in complete osteoblast-induction medium in presence of micron-sized
      biomaterial particles at various doses. 3-(4,5)-Dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide assay and lactate dehydrogenase assay were performed
      for cell proliferation and cytotoxicity. Differentiation and function of
      osteoblasts were evaluated by alkaline phosphatase (ALP), osteocalcin, RANKL,
      OSX, and Runx2 expressions. Murine interleukin-1 (IL-1), IL-6, and tumor necrosis
      factor-alpha in culture media were determined by enzyme-linked immunosorbent
      assay. Challenge with low doses of Ti, UHMWPE, or Co-Cr particles markedly
      promoted the bone marrow cell proliferation while high dose of Co-Cr
      significantly inhibited cell growth (p < 0.05). Cells challenged with low dose of
      PMMA or UHMWPE particles (0.63 mg/mL) exhibited strong ALP activity, whereas Ti
      and Co-Cr groups showed minimal effects (p < 0.05). UHMWPE and Ti particles also
      promoted higher expression of proinflammatory cytokines. Real-time polymerase
      chain reaction data suggested that cells treated with low dose (0.5 mg/mL)
      particles resulted in distinctly diminished RANKL expression compared to those
      exposed to high concentrated (3 mg/mL) particles. In conclusion, various types of
      wear debris particles behaved differently in the differentiation, maturation, and
      functions of osteogenic cells; and the particulate debris-interacted BMSCs may
      play an important role in the pathogenesis and process of the debris-associated
      aseptic prosthetic loosening.

PMID- 24039046
TI  - Hidden symmetry enables a 15-step total synthesis of pactamycin.

PMID- 24039048
TI  - Epidithiodiketopiperazine biosynthesis: a four-enzyme cascade converts
      glutathione conjugates into transannular disulfide bridges.
AB  - Enzyme quartet: Isolation of the first sulfur-bearing intermediate of the
      gliotoxin pathway in Aspergillus fumigatus and successful in vitro conversion of
      the bisglutathione adduct into an intact epidithiodiketopiperazine by a four
      enzyme cascade (including glutamyltransferase GliK and dipeptidase GliJ) revealed
      an outstanding adaptation of a primary metabolic pathway into natural product
      biosynthesis that is widespread in fungi. 

PMID- 24039049
TI  - Beyond the impasse? Systemic consultation and understanding complex cases.
AB  - BACKGROUND: Systemic consultation provides an opportunity for clinicians working
      with complex cases and behaviours of concern to reflect on interpersonal dynamics
      that may be inhibiting change. This approach to case review is drawn from
      systemic family therapy, a model that is gaining some acceptance within the field
      of intellectual disability. METHOD: Thematic analysis was used to explore the
      experience of eleven clinicians attending systemic consultation. Clinicians were
      experienced in behaviour support, had no prior experience in family therapy and
      presented with complex cases described as 'stuck'. RESULTS: Consultations were
      seen to have many benefits, including a heightened awareness of the interpersonal
      needs of both clients and carers and the development of a facilitative position
      and skills to apply to cases. Less experienced clinicians were more likely to
      feel overwhelmed by this less structured, more relationally oriented focus.
      CONCLUSIONS: Systemic consultation has the potential to augment behaviour
      support, enabling clinicians to understand and negotiate problematic
      interpersonal dynamics when responding to behavioural difficulties. Less
      experienced clinicians may require additional training and support in the
      systemic approach.

PMID- 24039050
TI  - The time to address the gorillas in the room is overdue.

PMID- 24039047
TI  - The molecular basis for kinesin functional specificity during mitosis.
AB  - Microtubule-based motor proteins play key roles during mitosis to assemble the
      bipolar spindle, define the cell division axis, and align and segregate the
      chromosomes. The majority of mitotic motors are members of the kinesin
      superfamily. Despite sharing a conserved catalytic core, each kinesin has
      distinct functions and localization, and is uniquely regulated in time and space.
      These distinct behaviors and functional specificity are generated by variations
      in the enzymatic domain as well as the non-conserved regions outside of the
      kinesin motor domain and the stalk. These flanking regions can directly modulate
      the properties of the kinesin motor through dimerization or self-interactions,
      and can associate with extrinsic factors, such as microtubule or DNA binding
      proteins, to provide additional functional properties. This review discusses the
      recently identified molecular mechanisms that explain how the control and
      functional specification of mitotic kinesins is achieved.

PMID- 24039051
TI  - Rhenium-catalyzed synthesis of 3-imino-1-isoindolinones by C-H bond activation:
      application to the synthesis of polyimide derivatives.

PMID- 24039052
TI  - Material properties of aged human mitral valve leaflets.
AB  - This study aimed to characterize the mechanical properties of aged human anterior
      mitral leaflets (AML) and posterior mitral leaflets (PML). The AML and PML
      samples from explanted human hearts (n = 21, mean age of 82.62 +/- 8.77-years
      old) were subjected to planar biaxial mechanical tests. The material stiffness,
      extensibility, and degree of anisotropy of the leaflet samples were quantified.
      The microstructure of the samples was assessed through histology. Both the AML
      and PML samples exhibited a nonlinear and anisotropic behavior with the
      circumferential direction being stiffer than the radial direction. The AML
      samples were significantly stiffer than the PML samples in both directions,
      suggesting that they should be modeled with separate sets of material properties
      in computational studies. Histological analysis indicated the changes in the
      tissue elastic constituents, including the fragmented and disorganized elastin
      network, the presence of fibrosis and proteoglycan/glycosaminoglycan infiltration
      and calcification, suggesting possible valvular degenerative characteristics in
      the aged human leaflet samples. Overall, stiffness increased and areal strain
      decreased with calcification severity. In addition, leaflet tissues from
      hypertensive individuals also exhibited a higher stiffness and low areal strain
      than normotensive individuals. There are significant differences in the
      mechanical properties of the two human mitral valve leaflets from this advanced
      age group. The morphologic changes in the tissue composition and structure also
      infer the structural and functional difference between aged human valves and
      those of animals.

PMID- 24039053
TI  - Antihyperglycemic effect of equol, a daidzein derivative, in cultured L6 myocytes
      and ob/ob mice.
AB  - SCOPE: Molecular mechanisms for the potential antihyperglycemic effect of equol
      remain to be elucidated. In this study, we investigated the in vitro effect of
      equol on glucose uptake, AMP-activated protein kinase (AMPK) phosphorylation, and
      glucose transporter 4 (GLUT4) translocation to plasma membrane in L6 myocytes,
      and its in vivo antihyperglycemic effect in obese-diabetic model ob/ob mice.
      METHODS AND RESULTS: Equol was found to promote glucose uptake, AMPK
      phosphorylation, and GLUT4 translocation detected by Western blotting analyses in
      L6 myotubes under a condition of insulin absence. Equol (0.05% in diet)
      suppressed the rise in serum glucose, cholesterol, triglyceride, and lipid
      peroxide concentrations and the hepatic triglyceride level as compared with those
      in the control group. Moreover, equol treatment suppressed the rises in fasting
      blood glucose level and improved the impaired glucose tolerance in ob/ob mice.
      Furthermore, equol treatment was demonstrated to improve expression of hepatic
      gluconeogenesis- and lipogenesis-related genes in terms of glucose and lipid
      metabolism. CONCLUSION: The hypoglycemic effect of equol is related to increased
      GLUT4 translocation to the plasma membrane via AMPK activation. In addition,
      equol suppresses the fasting blood glucose level and gene expression of hepatic
      enzymes related to glucose metabolism. These results strongly suggest that equol
      has antidiabetic potential.

PMID- 24039054
TI  - Severe congenital lipodystrophy and a progeroid appearance: Mutation in the
      penultimate exon of FBN1 causing a recognizable phenotype.
AB  - Recently, three marfanoid patients with congenital lipodystrophy and a neonatal
      progeroid appearance were reported. Although their phenotype was distinct from
      that of classic Marfan syndrome, they all had a truncating mutation in the
      penultimate exon, i.e., exon 64, of FBN1, the causative gene for Marfan syndrome.
      These patients might represent a new entity, but the exact phenotypic and
      genotypic spectrum remains unknown. Here, we report on a girl born prematurely
      who exhibited severe congenital lipodystrophy and a neonatal progeroid
      appearance. The patient exhibited a characteristic growth pattern consisting of
      an accelerated growth in height with a discrepant poor weight gain. She had a
      characteristic facial appearance with craniosynostosis. A mutation analysis
      identified c.8175_8182del8bp, p.Arg2726Glufs*9 in exon 64 of the FBN1 gene. A
      review of similar, recently reported patients revealed that the cardinal features
      of these patients include (1) congenital lipodystrophy, (2) premature birth with
      an accelerated linear growth disproportionate to the weight gain, and (3) a
      progeroid appearance with distinct facial features. Lines of molecular evidence
      suggested that this new progeroid syndrome represents a neomorphic phenotype
      caused by truncated transcripts with an extremely charged protein motif that
      escapes from nonsense-mediated mRNA decay, altering FBN1-TGF beta signaling,
      rather than representing the severe end of the hypomorphic phenotype of the FBN1
      TGF beta disorder spectrum. We propose that this marfanoid entity comprised of
      congenital lipodystrophy, a neonatal progeroid appearance, and a peculiar growth
      profile and caused by rare mutations in the penultimate exon of FBN1, be newly
      referred to as marfanoid-progeroid syndrome.

PMID- 24039056
TI  - Poly(alpha-hydroxy alkanoic acid)s derived from alpha-amino acids.
AB  - Biodegradable polyesters derived from hydrophobic amino acids are synthesized by
      various techniques, resulting in a wide range of molecular weights. The polymers
      are prepared via a) direct condensation with p-toluenesulfonic acid (PTSA) as
      catalyst, b) ring-opening polymerization (ROP) of O-carboxyanhydrides, and c) ROP
      of cyclic dilactones. The polymers obtained by the first method reach a molecular
      weight ranging from 1000 to 3000 Da, whereas those formed by the second and third
      method yield extended molecular weights of 15000-30000 Da. The purity of the
      monomers as well as their steric bulkiness are key factors affecting the
      polymerizability of cyclic monomers by ROP. Other parameters such as spatial ring
      alignment and proximity organization may also play a role.

PMID- 24039055
TI  - Factors associated with distance and time traveled to cleft and craniofacial
      care.
AB  - BACKGROUND: Information on travel distance and time to care for children with
      birth defects is lacking. We examined factors associated with travel distance and
      time to cleft care among children with orofacial clefts. METHODS: In 2006, a
      mail/phone survey was administered in English and Spanish to all resident mothers
      of children with orofacial clefts born 2001 to 2004 and identified by the North
      Carolina birth defects registry. We analyzed one-way travel distance and time and
      the extent to which taking a child to care was a problem. We used multivariable
      logistic regression to examine the association between selected sociodemographic
      factors and travel distance (<=60 miles and >60 miles) and time (<=60 min and >60
      min) to cleft care. RESULTS: Of 475 eligible participants, 51.6% (n = 245)
      responded. Of the respondents, 97.1% (n = 238) were the child's biological
      mother. Approximately 83% (n = 204) of respondents were non-Hispanic White; 33.3%
      (n = 81) were college educated; and 50.0% (n = 115) had private health insurance.
      One-way mean and median travel distances were 80 and 50 miles, respectively
      (range, 0-1058 miles). One-way mean and median travel times were 92 and 60 min,
      respectively (range, 5 min to 8 hr). After adjusting for selected
      sociodemographics, travel distance varied significantly by maternal education,
      child's age, and cleft type. Travel time varied significantly by child's age.
      Approximately 67% (n = 162) reported taking their child to receive care was not a
      problem. CONCLUSION: Approximately 48% of respondents traveled > 1 hr to receive
      cleft care. Increasing access to care may be important for improving health
      outcomes among this population.

PMID- 24039057
TI  - Bone-crack detection, targeting, and repair using ion gradients.
AB  - Bone cracks can be detected by utilizing the damaged matrix itself as both the
      trigger and the fuel. A crack in a material with a high mineral content such as
      bone generates ion gradients, which can be utilized for active targeting and
      treatment. This approach to targeting a biological structure augments current
      methods, which are focused on biomacromolecular interactions involving proteins
      and nucleic acids. 

PMID- 24039058
TI  - Total synthesis of a glycoglycerolipid from Meiothermus taiwanensis through a one
      pot glycosylation reaction and exploration of its immunological properties.
AB  - The total synthesis of a glycoglycerolipid isolate of Meiothermus taiwanensis and
      its truncated structural analogues is reported. Our synthesis employed DMF
      modulated and low-concentration glycosylation reactions for the construction of
      alpha- and beta-glycosidic bonds in the absence of participating protecting
      groups. Further simplification of the synthesis was achieved by employing a low
      concentration one-pot glycosylation procedure. Preliminary immunological studies
      showed that one of the truncated structural analogues suppressed the cytokine
      production of THP-1 monocytes. 

PMID- 24039060
TI  - Formation of a dinuclear copper(I) complex from the Clostridium-derived
      antibiotic closthioamide.

PMID- 24039059
TI  - Recovery of Chinese hamster ovary host cell proteins for proteomic analysis.
AB  - Identification and characterization of Chinese hamster ovary (CHO) host cell
      protein (HCP) impurities by proteomic techniques can aid bioprocess design and
      lead to more efficient development and improved biopharmaceutical manufacturing
      operations. Recovery of extracellular CHO HCP for proteomic analysis is
      particularly challenging due to the relatively low protein concentration and
      complex composition of media. In this article, we report the development of
      optimized protocols that improve proteome capture for CHO HCP. Eleven
      precipitation protocols were screened for protein recovery and optimized for a
      subset of precipitants by a design of experiments (DOE) approach. Because total
      protein recovery does not fully replicate a proteomics experiment, or detect non
      protein agents that may interfere with proteomic methods, a subset of
      precipitation conditions were compared by two-dimensional electrophoresis and
      liquid chromatography coupled with mass spectrometry, with optimized recovery
      shown to differ between the two proteomic methods. This work demonstrates broadly
      applicable methods that can be applied as initial steps to optimize sample
      preparation of any sample type for proteomic analysis, and presents optimized
      precipitation protocols for extracellular CHO HCP recovery, which can vary
      appreciably between gel-based and shotgun proteomic methods. 

PMID- 24039061
TI  - Gold clusters alloyed to nanoporous palladium surfaces as highly active
      bimetallic oxidation catalysts.

PMID- 24039062
TI  - Evaluation of a mPEG-polyester-based hydrogel as cell carrier for chondrocytes.
AB  - Temperature-sensitive hydrogels are attractive alternatives to porous cell-seeded
      scaffolds and is minimally invasive through simple injection and in situ gelling.
      In this study, we compared the performance of two types of temperature-sensitive
      hydrogels on chondrocytes encapsulation for the use of tissue engineering of
      cartilage. The two hydrogels are composed of methoxy poly(ethylene glycol)-
      poly(lactic-co-valerolactone) (mPEG-PVLA), and methoxy poly(ethylene glycol)
      poly(lactic- co-glycolide) (mPEG-PLGA). Osmolarity and pH were optimized through
      the manipulation of polymer concentration and dispersion medium. Chondrocytes
      proliferation in mPEG-PVLA hydrogels was observed as well as accumulation of GAGs
      and collagen. On the other hand, chondrocytes encapsulated in mPEG-PLGA hydrogels
      showed low viability and chondrogenesis. Also, mPEG-PVLA hydrogel, which is more
      hydrophobic, retained physical integrity after 14 days while mPEG-PLGA hydrogel
      underwent full degradation due to faster hydrolysis rate and more pronounced
      acidic self-catalyzed degradation. The mPEG-PVLA hydrogel can be furthered tuned
      by manipulation of molecular weights to obtain hydrogels with different swelling
      and degradation characteristics, which may be useful as producing a selection of
      hydrogels compatible with different cell types. Taken together, these results
      demonstrate that mPEG-PVLA hydrogels are promising to serve as three-dimensional
      cell carriers for chondrocytes and potentially applicable in cartilage tissue
      engineering.

PMID- 24039063
TI  - Caring for a child with learning disabilities over a prolonged period of time: an
      exploratory survey on the experiences and health of older parent carers living in
      Scotland.
AB  - BACKGROUND: The negative health impacts of prolonged caregiving are widely
      reported. However, there is a paucity of evidence concerning the impacts of a
      lifetime of caring on older parents of offspring with learning disabilities.
      DESIGN AND METHODS: An exploratory postal survey including the Medical Outcome
      Study (Short Form) 36 version 2 (SF-36v2) was completed by 100 older parent
      carers. The reported survey is part of a larger mixed method study including in
      depth interviews. RESULTS: The majority of respondents (n = 91) reported caring
      for 50 h or more per week with multiple caregiving duties. While the SF-36v2
      reported physical health of older parent carers to be similar to UK norms, their
      mental health was significantly reduced. IMPLICATIONS FOR PRACTICE: These
      important findings highlight the vulnerability of ageing parents of offspring
      with learning disabilities. This previously underreported situation warrants
      further investigation and urgent attention from health and social care agencies
      and professionals.

PMID- 24039064
TI  - Direct observation of cyclic carbenium ions and their role in the catalytic cycle
      of the methanol-to-olefin reaction over chabazite zeolites.
AB  - Carbenium ions in zeolites: Two important carbenium ions have been observed for
      the first time under working conditions of the methanol-to-olefins (MTO) reaction
      over chabazite zeolites using (13) C NMR spectroscopy. Their crucial roles in the
      MTO reaction cycles have been demonstrated by combining experiments and
      theoretical calculations. 

PMID- 24039065
TI  - Manganese-induced triplet blinking and photobleaching of single molecule cyanine
      dyes.
AB  - Irradiation of solutions of the cyanine dyes Cy3, Cy3B, and Cy5 in the presence
      of Mn(2+) causes an increase in the yield of formation of the triplet state of
      the dye. This results in increased photobleaching and triplet blinking.
      Experiments with other divalent ions and paramagnetic molecules suggest that the
      enhancement in the intersystem-crossing rate is related to the paramagnetic
      nature of the Mn(2+) cation. The results are consistent with a model in which the
      formation of a weak collisional complex between the dye and the ion results in
      mixing of the singlet and triplet states of the dye. These findings are
      particularly significant in single-molecule spectroscopy and super-resolution
      imaging methods, in which photobleaching and blinking play an important role. 

PMID- 24039066
TI  - Effects of sterilization treatments on bulk and surface properties of
      nanocomposite biomaterials.
AB  - With the continuous and expanding use of implantable biomaterials in a clinical
      setting, this study aims to elucidate the influence of sterilization techniques
      on the material surface and bulk properties of two polyurethane nanocomposite
      biomaterials. Both solid samples and porous membranes of nondegradable polyhedral
      oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU) and a
      biodegradable poly(caprolactone-urea) urethane (POSS-PCL) were examined.
      Sterilization techniques included conventional steam sterilization (autoclaving),
      gamma irradiation, and disinfection via incubating with ethanol (EtOH) for 10 min
      or 24 h. After treatment, the samples were examined using gel permeation
      chromatography (GPC), attenuated total reflectance Fourier transform infrared
      spectroscopy, and tensiometry. Cytotoxicity was evaluated through the culture of
      endothelial progenitor cells and the efficacy of sterilization method was
      determined by incubating each sample in tryptone soya broth and fluid
      thioglycollate medium for cultivation of microorganisms. Although EtOH did not
      affect the material properties in any form, the samples were found to be
      nonsterile with microbial growth detected on each of the samples. Gamma
      irradiation was not only effective in sterilizing both POSS-PCU and POSS-PCL but
      also led to minor material degradation and displayed a cytotoxic effect on the
      cultured cells. Autoclaving was found to be the optimal sterilization technique
      for both solid and porous membranes of the nondegradable POSS-PCU samples as it
      was successful in sterilizing the samples, displayed no cytotoxic side effects
      and did not degrade the material. However, the biodegradable POSS-PCL was not
      able to withstand the harsh environment during autoclaving, resulting in it
      losing all structural integrity.

PMID- 24039067
TI  - Effect of hydrion evolution by polylactic-co-glycolic acid coating on degradation
      rate of pure iron.
AB  - For biodegradable iron coronary stents, the major problem is the low degradation
      rate in body environment. In this study, a new strategy was proposed to increase
      the degradation rate of iron in vitro. The hydrion evolution was intended to be
      introduced into the degradation system to increase the degradation rate. To
      realize this strategy, polylactic-co-glycolic acid (PLGA) was coated onto the
      surface of pure iron. The degradation process and mechanism of pure iron coated
      with PLGA were investigated. The results showed that iron coated with PLGA
      exhibited higher degradation rate in the static immersion test all along. With
      the degradation of PLGA, the oligomers of PLGA could release abundant H(+) which
      could dissolve the ferrous oxide to make the electrolyte and oxygen to reach the
      surface of iron again and simultaneity trigger the hydrion evolution at the
      middle stage of the degradation. The study also revealed that the solution ions
      failed to permeate the PLGA coating and the deposition of calcium and phosphorus
      in the degradation layer was inhibited which further enhanced the degradation.

PMID- 24039068
TI  - The design of MACs (minimal actin cortices).
AB  - The actin cell cortex in eukaryotic cells is a key player in controlling and
      maintaining the shape of cells, and in driving major shape changes such as in
      cytokinesis. It is thereby constantly being remodeled. Cell shape changes require
      forces acting on membranes that are generated by the interplay of membrane
      coupled actin filaments and assemblies of myosin motors. Little is known about
      how their interaction regulates actin cell cortex remodeling and cell shape
      changes. Because of the vital importance of actin, myosin motors and the cell
      membrane, selective in vivo experiments and manipulations are often difficult to
      perform or not feasible. Thus, the intelligent design of minimal in vitro systems
      for actin-myosin-membrane interactions could pave a way for investigating actin
      cell cortex mechanics in a detailed and quantitative manner. Here, we present and
      discuss the design of several bottom-up in vitro systems accomplishing the
      coupling of actin filaments to artificial membranes, where key parameters such as
      actin densities and membrane properties can be varied in a controlled manner.
      Insights gained from these in vitro systems may help to uncover fundamental
      principles of how exactly actin-myosin-membrane interactions govern actin cortex
      remodeling and membrane properties for cell shape changes.

PMID- 24039069
TI  - Evaluation of renal function after successful treatment for unilateral, non
      syndromic Wilms tumor.
AB  - Impaired renal function may occur in experimental animals following surgical
      removal of most functioning renal tissue ("hyperfiltration injury"). Although end
      stage renal disease is uncommon among long-term survivors of unilateral, non
      syndromic Wilms tumor, concern has been expressed that there may be an increased
      risk of less serious, but progressive, renal function impairment among these
      individuals. The recent development of equations for estimating glomerular
      filtration rate (eGFR) has facilitated the study of renal function in Wilms tumor
      survivors. However, the estimating equations were developed to categorize
      individuals with chronic kidney disease and have significant limitations with
      regard to the accuracy of individual GFR estimates. These limitations must be
      considered when utilizing the estimating equations in cross-sectional or
      longitudinal evaluations of renal function in cohorts of patients who have been
      treated successfully for Wilms tumor or other childhood cancers.

PMID- 24039070
TI  - In vitro two-dimensional and three-dimensional tenocyte culture for tendon tissue
      engineering.
AB  - In order to examine the differentiation potential of the tenocytes expanded in
      our defined culture medium (reported previously) and the effect of sequential
      combination of the two culture conditions on human tenocytes, a two-dimensional
      and three-dimensional experimental approach was used. Human tenocytes were
      sequentially exposed to 1% fetal bovine serum (FBS) + 50 ng/ml platelet-derived
      growth factor-BB (PDGFBB ) + 50 ng/ml basic fibroblast growth factor (bFGF) for
      the first 14 days (expansion phase) followed by a further 14-day culture in the
      presence of 10 ng/ml transforming growth factor beta-3 plus 50 ng/ml insulin-like
      growth factor 1, but in the absence of serum (differentiation phase). The results
      showed that by sequential treatment of human tenocytes maintaining a long-term
      two-dimensional tenocyte culture in vitro for up to 28 days was possible. These
      findings were further verified using a three-dimensional scaffold (Bombyx silk)
      whereby the tendon-like constructs formed resembled macroscopically and
      microscopically the constructs formed in 10% FBS supplemented culture media and
      the human hamstring tendon. These findings were further substantiated using
      haematoxylin and eosin staining, scanning electron microscopy and by
      immunohistochemical detection of type I collagen. In addition, the mechanical
      properties of the three-dimensional constructs were determined to be
      significantly superior to that of the natural human hamstring tendon. This is the
      first report to demonstrate a possible approach in expanding and differentiating
      human tenocytes for tendon tissue engineering.

PMID- 24039071
TI  - Improved 2D-HPLC of red wine by incorporating pre-process signal-smoothing
      algorithms.
AB  - Two multidimensional HPLC separations of an Australian red wine are presented,
      >70% of the available separation space was used. A porous graphitic carbon (PGC)
      stationary phase was used as the first dimension in both separations with both RP
      core-shell and hydrophilic interaction chromatography fully porous columns used
      separately in the second dimension. To overcome peak analysis problems caused by
      signal noise and low detection limits, the data were pre-processed with penalised
      least-squares smoothing. The PGC * RP combination separated 85 peaks with a
      spreading angle of 71 degrees  and the PGC * hydrophilic interaction
      chromatography separated 207 peaks with a spreading angle of 80 degrees . Both 2D
      HPLC steps were completed in 76 min using a comprehensive stop-and-go approach. A
      smoothing step was added to peak-picking processes and was able to greatly reduce
      the number of false peaks present due to noise in the chromatograms. The required
      thresholds were not able to ignore the noise because of the small magnitude of
      the peaks; 1874 peaks were located in the non-smoothed PGC * RP separation that
      reduced to 227 peaks after smoothing was included. 

PMID- 24039072
TI  - Catalytic asymmetric homologation of alpha-ketoesters with alpha-diazoesters:
      synthesis of succinate derivatives with chiral quaternary centers.

PMID- 24039073
TI  - Death of a living liver donor: opening Pandora's box.

PMID- 24039074
TI  - Cucurbit[7]uril containers for targeted delivery of oxaliplatin to cancer cells.

PMID- 24039075
TI  - Hereditary deletion of the entire FAM20C gene in a patient with Raine syndrome.
AB  - Raine syndrome is an autosomal recessive disorder caused by mutations in the
      FAM20C gene that is characterized by generalized osteosclerosis with periosteal
      new bone formation and distinctive craniofacial dysmorphism. We report on a child
      who is homozygous for a 487-kb deletion in 7p22.3 that contains FAM20C. Both
      parents were heterozygous for the deletion. Our patient had the common
      craniofacial features as well as, uncommon features such as protruding tongue,
      short stature, and hypoplastic distal phalanges. In addition, he had wormian
      bones and pyriform aperture stenosis, features that are usually under diagnosed.
      It is clear that Raine syndrome has a wide range of expression and may not be
      lethal in the neonatal period. Furthermore, Raine cases due to whole gene
      deletion do not seem to have a major difference in the phenotype over those
      caused by various mutations.

PMID- 24039076
TI  - Intracellular thermometry by using fluorescent gold nanoclusters.
AB  - The "gold standard" for nanothermometry: The application of ultrasmall, near-IR
      emitting fluorescent gold nanoclusters (AuNCs) for temperature sensing has been
      explored. AuNC-based fluorescent nanothermometry features excellent thermal
      sensitivity and simultaneous temperature sensing and imaging in HeLa cells. 

PMID- 24039077
TI  - Surface-metastable phase-initiated seeding and ostwald ripening: a facile
      fluorine-free process towards spherical fluffy core/shell, yolk/shell, and hollow
      anatase nanostructures.
AB  - Versatile synthetic method: Monodisperse anatase microspheres with various
      complex morphologies have been synthesized by using a versatile fluorine-free
      solvothermal process in the presence of ammonia. Unambiguous evidence related to
      surface seeding and a subsequent hollowing process revealed an Ostwald ripening
      evolution process. 

PMID- 24039078
TI  - Identification of novel beta-lactoglobulin-derived peptides, wheylin-1 and -2,
      having anxiolytic-like activity in mice.
AB  - SCOPE: We found that thermolysin digest of beta-lactoglobulin, a major protein of
      bovine milk whey, exhibited anxiolytic-like activity in a behavioral experiment
      in mice, and then identified active components from the digest. METHODS AND
      RESULTS: In the elevated plus-maze test, thermolysin digest of beta-lactoglobulin
      had anxiolytic-like activity after intraperitoneal administration in mice. We
      identified several low-molecular-weight peptides in a fraction separated by
      reverse-phase HPLC having the most potent anxiolytic-like activities. Among them,
      Met-His and Met-Lys-Gly, corresponding to beta-lactoglobulin (145-146) and (7-9),
      had anxiolytic-like activity at a dose of 0.3-1 and 3 mg/kg, respectively, after
      intraperitoneal administration. We named Met-His and Met-Lys-Gly wheylin-1 and 
      2, respectively. Next, we focused on wheylin-1, a more potent peptide with
      anxiolytic-like activity than wheylin-2. Wheylin-1 (1 mg/kg) had anxiolytic-like
      activity after oral administration. In the open-field test, wheylin-1 was also
      active. The anxiolytic-like activity of wheylin-1 was blocked by bicuculline, an
      antagonist of gamma-amino butyric acid type A (GABA(A)) receptor, suggesting that
      wheylin-1 exhibited anxiolytic-like activity via the GABA(A) system. CONCLUSION:
      Novel beta-lactoglobulin-derived peptides, wheylin-1 and -2, may exhibit
      anxiolytic-like activities.

PMID- 24039079
TI  - Molecular interaction networks in the analyses of sequence variation and
      proteomics data.
AB  - Protein-protein interaction networks are typically generated in standard cell
      lines or model organisms as it is prohibitively difficult to record large
      interaction datasets from specific tissues or disease models at a reasonable
      pace. Although the interaction data are of high confidence, they thus do not
      reflect in vivo relationships as such. A wealth of physiologically relevant
      protein information, obtained under different conditions and from different
      systems, is available including information on genetic variation, protein levels,
      and PTMs. However, these data are difficult to assess comprehensively because the
      relationships between the entities remain elusive from the measurements. Here, we
      exemplarily highlight recent studies that gained deeper insight from genetic
      variation, protein, and PTM measurements using interaction information pointing
      toward the importance and potential of interaction networks for the
      interpretation of sequencing and proteomics data. 

PMID- 24039080
TI  - Economic feasibility of the sugar beet-to-ethylene value chain.
AB  - As part of a long-term strategy toward renewable feedstock, a feasibility study
      into options for the production of bioethylene by integrating the sugar beet-to
      ethanol-to-ethylene value chain. Seven business cases were studied and tested for
      actual economic feasibility of alternative sugar-to-ethanol-to-ethylene routes in
      comparison to fossil-fuel alternatives. An elaborate model was developed to
      assess the relevant operational and financial aspects of each business case. The
      calculations indicate that bioethylene from sugar beet is not commercially viable
      under current market conditions. In light of expected global energy and feedstock
      prices it is also reasonable to expect that this will not change in the near
      future. To consider biorenewable sources as starting material, they need to be
      low in cost (compared to sugar beets) and also require less capital and energy
      intensive methods for the conversion to chemicals. In general, European sugar
      prices will be too high for many chemical applications. Future efforts for in
      sugar-to-chemicals routes should, therefore, focus on integrated process routes
      and process intensification and/or on products that contain a significant part of
      the original carbohydrate backbone. 

PMID- 24039081
TI  - Respiratory outcomes of children with BPD and gastrostomy tubes during the first
      2 years of life.
AB  - OBJECTIVES: Infants with bronchopulmonary dysplasia (BPD) often undergo
      gastrostomy tube (GT) placement and/or Nissen fundoplication (Nissen) to improve
      weight gain and to attenuate chronic respiratory symptoms related to feeding
      difficulties. After initial hospitalization little is known how these children do
      with regard to respiratory symptoms when compared to children with BPD who did
      not receive GTs. This study was done to determine if differences in respiratory
      outcomes were associated with the presence of a GT or Nissen/GT in children with
      BPD during the first 2 years of life. METHODS: Children (n = 398) were recruited
      from the Johns Hopkins BPD Outpatient Clinic. Medical charts were reviewed and
      acute care usage and respiratory symptoms were assessed by caregiver
      questionnaires. RESULTS: Ninety-two children with BPD had GTs, with the majority
      placed by 6 months of age. Of children with GTs, 64.7% also had Nissen
      fundoplication. Children with Nissen/GTs were more likely to have birth weights
      <10th percentile and to be discharged on supplemental oxygen. After initial
      hospitalization, children with GTs and Nissen/GTs weaned off supplemental oxygen
      at significantly older ages than children without GTs. Children with Nissen/GTs
      also had more hospitalizations than children without GTs. Caregivers of children
      with GTs and Nissen/GTs reported similar respiratory symptoms as caregivers of
      children without GTs. CONCLUSION: Weaning off supplemental oxygen occurred later
      in children with GTs and Nissen/GTs compared to children without GTs. Although
      children with Nissen/GTs had more re-hospitalizations, there were no differences
      in reported respiratory symptoms between any of the groups by caregiver
      questionnaire.

PMID- 24039082
TI  - Graphene carrier for magneto-controllable bioelectrocatalysis.
AB  - A magnetically driven fuel-free graphene carrier loaded with redox-active cargo
      ferrocene as an electron mediator is fabricated for magneto-controllable
      bioelectrocatalysis. The activation and deactivation of redox-active cargo's
      redox activity by magnetically driven positioning of the graphene carrier with
      loaded ferrocene near and away from the conductive support can be employed for
      magneto-switchable bioelectrocatalyzed oxidation of glucose by glucose oxidase
      between active and inactive electrocatalytic states, respectively. 

PMID- 24039083
TI  - On the acidity and reactivity of highly effective chiral Bronsted acid catalysts:
      establishment of an acidity scale.
AB  - Stronger acid, higher speed: The pKa  values of a range of binol-derived Bronsted
      acids of three different types were measured and found to correlate directly with
      the catalytic properties of the acids: higher rate constants kI were observed for
      more acidic Bronsted acid catalysts (see plot; binol=1,1'-bi-2-naphthol). 

PMID- 24039084
TI  - Fluctuating asymmetry as risk marker for stress and structural defects in a
      toxicologic experiment.
AB  - Fluctuating asymmetry (the directionally random asymmetry of bilateral
      structures, FA) is commonly used as a measure of developmental instability, and
      may increase with stress. As several studies reported a relation between FA and
      developmental abnormalities, we investigate whether FA could be an additional
      perhaps more sensitive marker of developmental toxicity. The aim of this work is
      analyzing patterns of FA in multiple traits in a large dataset of rabbit fetuses,
      which were prenatally exposed to a toxic compound and sacrificed just before
      natural delivery. Gravid females were exposed to three doses of this compound,
      inducing abnormalities in the fetuses at the high dose only. The average FA,
      however, was already higher than control in rabbit fetuses of the low-dose group
      but did not further increase with higher concentrations. Moreover, the increase
      in FA differed between traits, with the hindlimbs showing the strongest response.
      In addition, we did not find any association between FA and the presence of fetal
      abnormalities at the individual level. Although these results suggest that FA may
      act as "an early warning system," we did not find a dose-response relationship
      with increasing stress and effects were trait-specific. Further testing is needed
      before FA may be considered as a sensitive marker in developmental toxicity
      studies. 

PMID- 24039085
TI  - Moonlighting microtubule-associated proteins: regulatory functions by day and
      pathological functions at night.
AB  - The sensing, integrating, and coordinating features of the eukaryotic cells are
      achieved by the complex ultrastructural arrays and multifarious functions of the
      cytoskeletal network. Cytoskeleton comprises fibrous protein networks of
      microtubules, actin, and intermediate filaments. These filamentous polymer
      structures are highly dynamic and undergo constant and rapid reorganization
      during cellular processes. The microtubular system plays a crucial role in the
      brain, as it is involved in an enormous number of cellular events including cell
      differentiation and pathological inclusion formation. These multifarious
      functions of microtubules can be achieved by their decoration with
      proteins/enzymes that exert specific effects on the dynamics and organization of
      the cytoskeleton and mediate distinct functions due to their moonlighting
      features. This mini-review focuses on two aspects of the microtubule
      cytoskeleton. On the one hand, we describe the heteroassociation of
      tubulin/microtubules with metabolic enzymes, which in addition to their catalytic
      activities stabilize microtubule structures via their cross-linking functions. On
      the other hand, we focus on the recently identified moonlighting tubulin
      polymerization promoting protein, TPPP/p25. TPPP/p25 is a microtubule-associated
      protein and it displays distinct physiological or pathological (aberrant)
      functions; thus it is a prototype of Neomorphic Moonlighting Proteins. The
      expression of TPPP/p25 is finely controlled in the human brain; this protein is
      indispensable for the development of projections of oligodendrocytes that are
      responsible for the ensheathment of axons. The nonphysiological, higher or lower
      TPPP/p25 level leads to distinct CNS diseases. Mechanisms contributing to the
      control of microtubule stability and dynamics by metabolic enzymes and TPPP/p25
      will be discussed.

PMID- 24039086
TI  - Repetitive Arg-Gly-Asp peptide as a cell-stimulating agent on electrospun
      poly(epsilon-caprolactone) scaffold for tissue engineering.
AB  - Electrospun scaffolds derived from poly(epsilon-caprolactone) (PCL), a well known
      biodegradable material, have an architecture that is suitable for hosting cells.
      However, their biomedical applications are restricted because these scaffolds
      lack the bioactivity necessary to stimulate cell responses. In this work, a
      repetitive Arg-Gly-Asp (rRGD) peptide was produced as a cell-stimulating agent to
      provide the PCL scaffold with bioactivity. DNA encoding rRGD was amplified by
      polymerase chain reaction using overlap primers without a DNA template, and
      cloned into a protein expression vector to produce a His-tag fusion peptide. In
      an in vitro cell adhesion assay, the purified rRGD peptide, comprising 30 RGD
      repeats, promoted a 1.5-fold greater cell adhesion than the commercial tripeptide
      RGD. The rRGD peptide was immobilized onto an electrospun PCL scaffold that had
      been pretreated with argon plasma and graft-polymerized with acrylic acid.
      Fourier transform infrared (FTIR) analysis indicated that covalently linked rRGD
      peptide was present on the scaffold. The PCL scaffold with immobilized rRGD
      showed significantly changed hydrophilic properties and an enhanced adhesion and
      proliferation of mouse fibroblast cells by 2.3- and 2.9-fold, respectively,
      compared to the PCL scaffold alone. Through its ability to promote cell adhesion
      and proliferation, the rRGD peptide has great potential as a stimulant for
      improving the suboptimal cell-matrix interaction of polymeric scaffolds for
      tissue engineering applications. 

PMID- 24039087
TI  - A powerful hydrogen-bond-donating organocatalyst for the enantioselective
      intramolecular oxa-Michael reaction of alpha,beta-unsaturated amides and esters.
AB  - Tuning the organocatalyst: An unprecedented enantioselective intramolecular oxa
      Michael reaction of unactivated alpha,beta-unsaturated amides and esters
      catalyzed by a powerful hydrogen-bond-donating organocatalyst has been developed.
      Furthermore, the products obtained from this reaction have been used for the
      straightforward asymmetric synthesis of several natural products and biologically
      important compounds. 

PMID- 24039088
TI  - More than meets the eye: The evolving phenotype of Weill-Marchesani syndrome
      diagnostic confusion with geleophysic dysplasia.
AB  - The criteria for diagnosing and distinguishing between Weill-Marchesani syndrome
      (WMS) and geleophysic dysplasia (GD) are inexact and often overlap. We report the
      clinical findings and evolving phenotype for a period of 18 years in a patient
      whose diagnosis, and distinguishing characteristics, transformed from GD to WMS.
      Molecular testing demonstrated novel mutations in the ADAMTS10 gene confirming a
      diagnosis of autosomal recessive WMS in the proposita. We further report on
      phenotypic features not classically linked to WMS. These findings indicate that
      the Weill-Marchesani phenotype may be developed and is not always apparent in
      early childhood.

PMID- 24039089
TI  - Protective effects of coffee against induction of DNA damage and pre-neoplastic
      foci by aflatoxin B1.
AB  - SCOPE: Aim of the study was to investigate the protective properties of coffee
      towards aflatoxin B1 (AFB1) induced formation of pre-neoplastic hepatic foci and
      the identification of the constituents and molecular mechanisms that account for
      these effects. MATERIALS AND METHODS: Rats consumed three different brews and
      were subsequently treated with AFB1 (0.75 mg/kg b.w. intraperitoneally). Ten
      weeks later, the numbers and areas of hepatic foci were determined. Furthermore,
      the impact of the brews on AFB1-induced DNA damage was quantified in single cell
      gel electrophoresis assays and the activities of drug metabolising enzymes and
      glutathione-related parameters were monitored. Additionally, single cell gel
      electrophoresis assay experiments were conducted with pure caffeine. CONCLUSION:
      All brews reduced the frequencies of the hepatic foci. The most pronounced
      protection (reduction 82%) was seen with the caffeine containing metal and paper
      filtered brews. DNA migration was reduced between 65 and 75% with the caffeine
      containing brews. In additional experiments, clear protective effects were found
      with caffeine at dose levels that corresponded to those contained in the coffee.
      This observation indicates that the alkaloid accounts partly for the protective
      effects of coffee. Furthermore, our findings indicate that induction of UDP
      glucuronosyltransferase contributes to the chemopreventive effects of coffee
      since all brews increased the activity of this detoxifying enzyme.

PMID- 24039090
TI  - Center variation in the use of nonstandardized model for end-stage liver disease
      exception points.
AB  - The Model for End-Stage Liver Disease (MELD) score is an imperfect prognosticator
      of waitlist dropout, so transplant centers may apply for exception points to
      increase a waitlist candidate's priority on the waitlist. Exception applications
      are categorized as recognized exceptional diagnoses (REDs; eg, hepatocellular
      carcinoma) and non-REDs (eg, cholangitis). Although prior work has demonstrated
      regional variation in the use of exceptions, no work has examined the between
      center variability. We analyzed all new waitlist candidates from February 27,
      2002 to June 3, 2011 to explore variations in the use of non-REDs, for which no
      strict exception criteria exist. There were 58,641 new waitlist candidates, and
      4356 (7.4%) applied for a non-RED exception. The number of applications increased
      steadily over time, as did the approval rates for such applications: from <50% in
      2002 to nearly 75% in 2010. When we adjusted for patient factors, there was
      significant variability (P < 0.001) in the use of non-RED exceptions in 8 of 11
      United Network for Organ Sharing (UNOS) regions and in the approval of these
      exceptions in 6 of 11 UNOS regions. The variability in the use and approval of
      non-REDs was clinically significant: waitlist candidates with approved exceptions
      were significantly more likely to undergo transplantation (68.3% versus 53.4%, P
      < 0.001) and were less likely to be removed for death or clinical deterioration
      (10.4% versus 16.2%, P < 0.001). Increased median MELD score at transplantation
      within a donor service area was the only center factor associated with increased
      odds of applying for exceptions, while no center factors were associated with
      having non-RED exceptions approved. Further work is needed to identify other
      sources of variation to ensure the appropriate and equitable use of non-RED
      exceptions.

PMID- 24039091
TI  - Effects of parathyroid hormone 1-34 on osteogenic and chondrogenic
      differentiation of human fracture haematoma-derived cells in vitro.
AB  - Parathyroid hormone (PTH) 1-34 has been shown to accelerate fracture healing.
      Previously, we reported that progenitor cells with osteogenic and chondrogenic
      potential exist in human fracture haematoma, suggesting that the fracture
      haematoma-derived progenitor cells (HCs) contribute to fracture healing. However,
      there has been no study investigating the effect of PTH on HCs. We investigated
      the effect of pulsatile and continuous PTH treatment on human fracture HCs in
      vitro. HCs were isolated from seven patients. The HCs were divided into four
      groups: growth medium; control [osteogenic medium (OM) without PTH]; PTH-C (OM
      with continuous PTH); and PTH-P (OM with pulsatile PTH) groups. Osteogenic
      differentiation potential and proliferation of HCs were compared among the four
      groups. For chondrogenesis, the HCs were divided into two groups: control
      [chondrogenic medium (CM) without PTH]; and PTH-C (CM with continuous PTH)
      groups, and chondrogenic differentiation potential was analysed. PTH treatment
      did not affect cell proliferation, regardless of the mode of administration.
      Osteogenic activity was also not significantly affected by continuous PTH
      treatment but significantly inhibited by pulsatile PTH treatment. Conversely,
      chondrogenic differentiation was significantly inhibited by continuous PTH
      treatment. Our results revealed that PTH treatment on HCs, either continuous or
      pulsatile, does not exhibit any positive effect, and indicates that exogenous PTH
      administration after fracture has no effect on HCs. PTH may not have a positive
      effect at the fracture site during the early stage of fracture healing in which
      haematoma formation occurs. Copyright (c) 2013 John Wiley & Sons, Ltd.

PMID- 24039092
TI  - Total synthesis of (+)-crotogoudin.
AB  - Fellowship of the ring: The first total synthesis of (+)-crotogoudin, a 3,4-seco
      atisane diterpenoid natural product, is reported. Asymmetric access to the
      bicyclo[2.2.2]octane core is achieved through a desymmetrization of a meso
      diketone with baker's yeast (LG=leaving group, PG=protecting group). A SmI2 
      induced radical cyclopropane-opening/annulation/elimination cascade affords the
      suitably decorated tetracyclic structure of (+)-crotogoudin. The synthesis led to
      revision of the reported optical rotation of the natural product and to
      assignment of its absolute configuration as an ent-atisane (5R,10R). 

PMID- 24039093
TI  - A quantum probability perspective on borderline vagueness.
AB  - The term "vagueness" describes a property of natural concepts, which normally
      have fuzzy boundaries, admit borderline cases, and are susceptible to Zeno's
      sorites paradox. We will discuss the psychology of vagueness, especially
      experiments investigating the judgment of borderline cases and contradictions. In
      the theoretical part, we will propose a probabilistic model that describes the
      quantitative characteristics of the experimental finding and extends Alxatib's
      and Pelletier's () theoretical analysis. The model is based on a Hopfield network
      for predicting truth values. Powerful as this classical perspective is, we show
      that it falls short of providing an adequate coverage of the relevant empirical
      results. In the final part, we will argue that a substantial modification of the
      analysis put forward by Alxatib and Pelletier and its probabilistic pendant is
      needed. The proposed modification replaces the standard notion of probabilities
      by quantum probabilities. The crucial phenomenon of borderline contradictions can
      be explained then as a quantum interference phenomenon. 

PMID- 24039094
TI  - Separation of aromatic amines by an open-tubular capillary electrochromatography
      method.
AB  - A new and simple open-tubular CEC (OT-CEC) method with a novel diblock copolymer
      poly(butyl methacrylate)71 -block-poly(glycidyl methacrylate)9 as the coating
      based on its self-assembled properties has been developed. Compared with the bare
      capillary, this coating could act as a surfactant and improve the separation
      efficiency of aromatic amines. Meanwhile, the effects of pH value, buffer
      concentration, and the copolymer block ratio on the separation efficiencies were
      investigated in detail. It has been found that the three tested aromatic amines
      could be baseline separated by the OT-CEC method with the cooperation of SDS. The
      proposed OT-CEC method showed good repeatability with RSDs <3.2% for testing the
      EOF. Moreover, it was also well validated by satisfactory linearity and favorable
      recovery, which ensured its successful application in the separation of aromatic
      amines in nail polish samples. The results revealed the potential applicability
      of the OT-CEC method in cosmetic analysis. 

PMID- 24039095
TI  - Where does it vibrate? Raman spectromicroscopy on a single molecule.
AB  - Tip-enhanced Raman spectroscopy combines scanning probe techniques with Raman
      spectroscopy. Latest developments permit the chemical mapping of individual
      adsorbed molecules by monitoring molecular vibrations with sub-nanometer
      resolution. Increased efficiency and reduced photodegradation make this method
      suitable for studies of adsorbed organic and biomolecules in surface science,
      catalysis, biochemistry, and related fields. 

PMID- 24039096
TI  - Do pediatric hematology/oncology (PHO) fellows receive communication training?
AB  - PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) has
      established communication as a core competency for physicians in training.
      However, data suggest that most pediatric residents perceive inadequate training
      in the delivery of bad news and the majority of former trainees in pediatric
      oncology received no formal training in the delivery of bad news during
      fellowship. The study examines communication training in ACGME accredited US
      pediatric hematology-oncology (PHO) fellowship programs. METHODS: An online
      survey was distributed to 315 PHO fellows in training via the American Society of
      Pediatric Hematology/Oncology (ASPHO) fellow email registry. Each fellow received
      an initial request to participate and 2 reminders, while participation was
      encouraged through a random incentive drawing. RESULTS: One hundred and ten
      fellows (35%) responded. Eighty percent of respondents perceived communication
      training to be important to fellow education, however only 32% reported receiving
      communication training (other than direct observation). The most common reported
      teaching method of fellowship communication training was formal lecture (42%).
      Twenty-three percent of respondents reported neither communication training nor
      frequent feedback on their communication skills from faculty observation. This
      same group was the least satisfied with their programs' approach to teaching
      communication (P < 0.001). CONCLUSIONS: There is limited communication training
      in PHO fellowships despite ACGME requirements and fellows' interest in this
      training. Didactic learning remains the most frequently described training
      method, yet educational theory identifies the limitation of didactic lectures
      alone. Communication training employing novel teaching methods and emphasizing
      communication challenges identified by fellows should be developed and evaluated.

PMID- 24039097
TI  - Efficient organic dye-sensitized solar cells: molecular engineering of donor
      acceptor-acceptor cationic dyes.
AB  - Three metal-free donor-acceptor-acceptor sensitizers with ionized pyridine and a
      reference dye were synthesized, and a detailed investigation of the relationship
      between the dye structure and the photophysical and photoelectrochemical
      properties and the performance of dye-sensitized solar cells (DSSCs) is
      described. The ionization of pyridine results in a red shift of the absorption
      spectrum in comparison to that of the reference dye. This is mainly attributable
      to the ionization of pyridine increasing the electron-withdrawing ability of the
      total acceptor part. Incorporation of the strong electron-withdrawing units of
      pyridinium and cyano acrylic acid gives rise to optimized energy levels,
      resulting in a large response range of wavelengths. When attached to TiO2 film,
      the conduction band of TiO2 is negatively shifted to a different extent depending
      on the dye. This is attributed to the electron recombination rate between the
      TiO2 film and the electrolyte being efficiently suppressed by the introduction of
      long alkyl chains and thiophene units. DSSCs assembled using these dyes show
      efficiencies as high as 8.8 %. 

PMID- 24039098
TI  - Pulmonary interstitial glycogenosis in a patient ultimately diagnosed with Noonan
      syndrome.
AB  - We describe an infant prenatally diagnosed with hydrops fetalis ultimately found
      to have Noonan syndrome (NS). Prior to genetic confirmation of diagnosis, lung
      biopsy was performed which revealed widespread pulmonary interstitial
      glycogenosis (PIG), abnormal alveolarization, and mild inflammation. Although
      genetic alterations have been identified in NS, the mutations are heterogeneous
      and the diagnosis remains one of clinical suspicion. The combination of PIG and
      NS has not yet been documented in the literature. While the underlying
      pathophysiologic mechanism of PIG is unclear, we suggest that the mitogen
      activated protein kinase signal transduction pathway members (PTPN11, KRAS, SOS1,
      RAF1, SHOC2, NRAS) involved in cellular growth factor signaling, which are
      affected in NS, can provide clues. In addition, this case demonstrates that
      empiric corticosteroids can be considered in complicated cases since biopsy did
      reveal an inflammatory component, not typically noted in PIG.

PMID- 24039099
TI  - Polymer-free Vertical Transfer of Silicon Nanowires and their Application to
      Energy Storage.
AB  - Silicon nanowires (SiNWs) for use as lithium-ion battery (LIB) anode materials
      have been studied for their one-dimensional (1D) properties and ability to
      accommodate large volume changes and avoid rapid capacity fading during cycling.
      Although the vertical transfer of SiNWs from their original substrate onto a
      conducting electrode is very important, to date, there has been no report of a
      direct integration method without polymer binders. Here, we propose for the first
      time a vertical transfer method for SiNWs grown on a Si substrate directly to the
      current-collecting electrode without using a polymer adhesive for the use as a
      binder-free LIB anode. The vertical SiNWs produced using a low-cost wafer-scale
      metal-assisted chemical etching (MaCE) process have been successfully transferred
      directly to a copper electrode coated with a thin Ag layer by using a simple hot
      pressing method. When evaluated as an LIB anode without using conventional
      polymeric binder and a conducting additive, the transferred vertically aligned
      SiNWs showed a high specific capacity (~2150 mAh g(-1) ) and excellent rate
      performance. It is believed that the anode-manufacturing process is simple and
      fast, thus enabling a large-scale production that is of low-cost, broadly
      applicable, and provides new avenues for the rational engineering of Si-based
      electrode materials with enhanced power density and conductivity. 

PMID- 24039100
TI  - O2 binding to heme is strongly facilitated by near-degeneracy of electronic
      states.
AB  - This paper reports the computed O2 binding to heme, which for the first time
      explains experimental enthalpies for this process of central importance to
      bioinorganic chemistry. All four spin states along the relaxed Fe-O2-binding
      curves were optimized using the full heme system with dispersion, thermodynamic,
      and scalar-relativistic corrections, applying several density functionals. When
      including all these physical terms, the experimental enthalpy of O2 binding (-59
      kJ mol(-1)) is closely reproduced by TPSSh-D3 (-66 kJ mol(-1)). Dispersion
      changes the potential energy surfaces and leads to the correct electronic singlet
      and heptet states for bound and dissociated O2. The experimental activation
      enthalpy of dissociation (~82 kJ mol(-1)) was also accurately computed (~75 kJ
      mol(-1)) with an actual barrier height of ~60 kJ mol(-1) plus a vibrational
      component of ~10 and ~5 kJ mol(-1) due to the spin-forbidden nature of the
      process, explaining the experimentally observed difference of ~20 kJ mol(-1) in
      enthalpies of binding and activation. Most importantly, the work shows how the
      nearly degenerate singlet and triplet states increase crossover probability up to
      ~0.5 and accelerate binding by ~100 times, explaining why the spin-forbidden
      binding of O2 to heme, so fundamental to higher life forms, is fast and
      reversible.

PMID- 24039101
TI  - Synergistic modulation of surface interaction to assemble metal nanoparticles
      into two-dimensional arrays with tunable plasmonic properties.
AB  - A simple strategy based on the synergistic modulation of inter-particle and
      substrate-particle interaction is applied for the large-scale fabrication of two
      dimensional (2D) Au and Ag nanoparticle arrays. The surface charge of the
      substrate is used to redistribute the double layer electric charges on the
      particles and to modulate the inter-particle distance within the 2D nanoparticle
      arrays on the substrate. The resultant arrays, with a wide range of inter
      particle distances, display tunable plasmonic properties. It can be foreseen that
      such 2D nanoparticle arrays possess potential applications as multiplexed
      colorimetric sensors, integrated devices and antennas. Herein, it is demonstrated
      that these arrays can be employed as wavelength-selective substrates for
      multiplexed acquisition of surface-enhanced Raman scattering (SERS) spectra. This
      simple one step process provides an attractive and low cost strategy to produce
      high quality and large area 2D ordered arrays with tunable properties. 

PMID- 24039102
TI  - Binding of a designed anti-cancer drug to the central cavity of an RNA three-way
      junction.
AB  - Getting to the heart of it: Co-crystallization of an RNA three-way junction with
      a cylindrical di-iron(II)-based anti-cancer drug (green) results in pi-stacking
      interactions between the cylinder and the central base pairs of the RNA
      structure. The shape, size, and cationic nature of the cylinder were found to be
      responsible for this perfect fit. Native gel electrophoresis studies confirmed
      stabilization of the RNA three-way junction by the iron(II) cylinder. 

PMID- 24039103
TI  - Analysis of flexural rigidity of actin filaments propelled by surface adsorbed
      myosin motors.
AB  - Actin filaments are central components of the cytoskeleton and the contractile
      machinery of muscle. The filaments are known to exist in a range of
      conformational states presumably with different flexural rigidity and thereby
      different persistence lengths. Our results analyze the approaches proposed
      previously to measure the persistence length from the statistics of the winding
      paths of actin filaments that are propelled by surface-adsorbed myosin motor
      fragments in the in vitro motility assay. Our results suggest that the
      persistence length of heavy meromyosin propelled actin filaments can be estimated
      with high accuracy and reproducibility using this approach provided that: (1) the
      in vitro motility assay experiments are designed to prevent bias in filament
      sliding directions, (2) at least 200 independent filament paths are studied, (3)
      the ratio between the sliding distance between measurements and the camera pixel
      size is between 4 and 12, (4) the sliding distances between measurements is less
      than 50% of the expected persistence length, and (5) an appropriate cut-off value
      is chosen to exclude abrupt large angular changes in sliding direction that are
      complications, e.g., due to the presence of rigor heads. If the above precautions
      are taken the described method should be a useful routine part of in vitro
      motility assays thus expanding the amount of information to be gained from these.

PMID- 24039105
TI  - Chiral silanediols in anion-binding catalysis.
AB  - A perfect pair: Silanediols are effective catalysts for the addition of silyl
      ketene acetals to N-acylisoquinolinium ions. Importantly, this is the first
      example of a silanediol plausibly participating in anion-binding catalysis, a
      relatively new direction in the field of hydrogen-bond-donor catalysis. The
      chiral, enantiopure C2 -symmetric silanediol 1 catalyzes enantioselective
      transformations. 

PMID- 24039104
TI  - Teratology study of amide derivatives of branched aliphatic carboxylic acids with
      4-aminobenzensulfonamide in NMRI mice.
AB  - BACKGROUND: Valproic acid (VPA), widely used to treat epilepsy, bipolar
      disorders, and migraine prophylaxis, is known to cause neural tube and skeletal
      defects in humans and animals. Aminobenzensulfonamide derivatives of VPA with
      branched aliphatic carboxylic acids, namely 2-methyl-N-(4-sulfamoyl-phenyl)
      pentanamide (MSP), 2-ethyl-N-(4-sulfamoyl-phenyl)-butyramide (ESB), 2-ethyl-4
      methyl-N-(4-sulfamoyl-phenyl)-pentanamide (EMSP), and 2-ethyl-N-(4-sulfamoyl
      benzyl)-butyramide (ESBB), have shown more potent anticonvulsant activity than
      VPA in preclinical testing. Here, we investigated the teratogenic effects of
      these analogous compounds of VPA in NMRI mice. METHODS: Pregnant NMRI mice were
      given a single subcutaneous injection of either VPA at 1.8 or 3.6 mmol/kg, or
      MSP, ESB, EMSP, or ESBB at 1.8, 3.6, or 4.8 mmol/kg on gestation day (GD) 8.
      Cesarean section was performed on GD 18, and the live fetuses were examined for
      external and skeletal malformations. RESULTS: Compared with VPA, which induced
      neural tube defects (NTDs) in fetuses at 1.8 and 3.6 mmol/kg, the analog
      derivatives induced no NTDs at dose levels up to 4.8 mmol/kg (except for a single
      case of exencephaly at 4.8 mmol/kg MSP). Skeletal examination showed several
      abnormalities mainly at the axial skeletal level with VPA at 1.8 mmol/kg. Fused
      vertebrae and/or fused ribs were also observed with MSP, ESB, EMSP, and ESBB,
      they were less severe and seen at a lower incidence that those induced by VPA at
      the same dose level. CONCLUSIONS: In addition to exerting more potent preclinical
      antiepileptic activity, teratology comparison indicates that
      aminobenzensulfonamide analogs are generally more weakly teratogenic than VPA.

PMID- 24039106
TI  - Effect of a beta-TCP collagen composite bone substitute on healing of drilled
      bone voids in the distal femoral condyle of rabbits.
AB  - In this study, we tested the performance and biocompatibility of a composite of
      beta-tricalcium phosphate (beta-TCP) to collagen as a bone void filler
      (Cerasorb((r)) Ortho Foam) in a rabbit distal femoral condyle model. beta-TCP is
      a completely resorbable synthetic calcium phosphate and the addition of a
      collagen matrix couples the osteoconductive effects of the two components.
      Furthermore, the malleable properties of the implant material during surgical
      applications for shape control will be enhanced. A critical size defect of 6 mm
      in diameter and 10 mm in depth was drilled into each distal femur of the rabbits.
      One hole was filled with the test substance and the other was left empty for
      control. After 1, 3, and 6 months the animals were killed and the degree of bone
      healing analyzed. In total, 18 animals were investigated. When the beta-TCP
      composite was used, histological, histomorphometric, and biomechanical
      evaluations revealed significantly better bone healing in terms of quantity and
      quality of the newly formed bone. Moreover, no signs of inflammation were
      observed in the animals and no allergic or foreign body reaction was noted. This
      suggests high biocompatibility and osteoconductivity of the investigated material
      to a bone void in an immune responsive species.

PMID- 24039107
TI  - Interleukin-28B and fibrosing cholestatic hepatitis in posttransplant hepatitis
      C: a case-control study and literature review.
AB  - Chronic hepatitis C (CHC)-related cirrhosis is the leading indication for liver
      transplantation (LT). However, the recurrence of a hepatitis C virus (HCV)
      infection after transplantation is universal and is associated with worse
      outcomes. Fibrosing cholestatic hepatitis (FCH) is a particularly severe
      manifestation of a recurrent HCV infection and frequently results in graft
      failure and death. The identification of risk factors for FCH is important but
      has been limited by the low frequency of FCH. The interleukin-28B (IL-28B)
      genotype is important in an HCV infection: it is related to the clinical severity
      of an acute infection and may play a role in the development of FCH as well. Two
      hundred seventy-two consecutive LT cases for CHC were studied at a single
      institution. Consensus criteria were used to define an FCH cohort. The remainder
      of the study population served as a control group. The IL-28B genotype (at the
      rs12979860 locus) from both the donor and the recipient was determined, and other
      clinically relevant data were tabulated. A nonparametric statistical analysis was
      performed. Twelve cases of FCH were identified, and they were compared to a
      control group of 260 LT cases without FCH. A detailed analysis of clinical
      characteristics, including treatment responses and outcomes, was tabulated. FCH
      was associated with the earlier recurrence of HCV infections, higher HCV viral
      loads, and lower levels of immunosuppressive medications. There was a
      nonsignificant increase in recipient IL-28B non-CC genotypes in cases developing
      FCH. In conclusion, a high HCV viral load and earlier recurrence were identified
      as risk factors for FCH. It is still unclear what role immunosuppression plays in
      the pathogenesis of FCH and whether IL-28B polymorphisms constitute a risk
      factor. Collaborative studies with larger numbers of study subjects are needed in
      order to define these issues.

PMID- 24039108
TI  - Cognitive function in children with brain tumors in the first year after
      diagnosis compared to healthy matched controls.
AB  - BACKGROUND: Improved survival of children with brain tumors (BTs) has increased
      focus on ameliorating morbidity. To reduce the risk of progressive cognitive
      decline, remedial strategies need to be instituted early, based upon accurate
      appraisal of need, yet few studies have investigated cognition in BT children
      early post-diagnosis. The study aims were to investigate cognition in children
      with primary BTs 1, 6, and 12 months post-diagnosis compared with healthy
      children, exploring the impact of disease and treatment variables. METHODS: Forty
      eight children aged 2-16 years with primary BTs, referred to a Regional
      Neurosurgical Unit over the 2-year study period were eligible for enrollment. The
      "best friends" model was used to recruit matched controls. Cognition was assessed
      using age-appropriate Wechsler Intelligence scales; Children's Memory Scale; Test
      of Everyday Attention for Children, and Wechsler Quicktest. RESULTS: Patients
      with BTs had significantly reduced performance compared to controls early post
      diagnosis in tests of Performance IQ, processing speed, verbal and visual memory,
      and selective attention. Improved performance over 12 months was seen in patients
      with BTs although also, for some measures, in controls. Significant deficits in
      cognitive performance were seen one year post-diagnosis for Verbal IQ; processing
      speed, visual and verbal immediate memory, and selective attention.
      Infratentorial site, high tumor grade, hydrocephalus, radiotherapy, and
      chemotherapy were associated with poorer functioning. CONCLUSION: Early cognitive
      impairment is present in BT children, sometimes prior to
      radiotherapy/chemotherapy treatment, and is associated with hydrocephalus, high
      tumor grade and infratentorial site. Future studies should investigate the role
      of early rehabilitation in improving cognition.

PMID- 24039109
TI  - 6-Shogaol inhibits chondrocytes' innate immune responses and cathepsin-K
      activity.
AB  - SCOPE: Ginger has long been used in traditional Asian medicine to treat
      osteoarthritis. Indeed, scientific research has reported that ginger derivatives
      (GDs) have the potential to control innate immune responses. Given the widespread
      use and demonstrated properties of GDs, we set out to study their anti
      inflammatory and anticatabolic properties in chondrocytes. METHODS AND RESULTS: 6
      shogaol (6-S), the most active GD, was obtained from ginger. 6-S was not toxic as
      measured by MTT assay, and inhibited NO production and IL-6 and MCP-1 induced
      gene expression in LPSbut not in IL-1beta-stimulated chondrocytes. 6-S also
      inhibited LPS-mediated ERK1/2 activation as well as NOS2 and MyD88 induced
      expression as determined by Western blot. Moreover, zymography revealed that 6-S
      inhibited matrix metalloproteinases (MMP) 2/9 induction in LPS-treated cells.
      Hydrated 6-S was modified to obtain a compound (SSi6) without 6-S potential anti
      inflammatory properties. Both 6-S and SSi6 inhibited cathepsin-K activity.
      CONCLUSION: 6-S blocked TLR4-mediated innate immune responses and MMP induction
      in chondrocytes. These results, together with GDs-mediated cathepsin-K
      inhibition, suggest the potential for GDs use against cartilage and bone
      degradation. Therefore, considering that clinical trials involving oral
      administration of ginger achieved relevant nontoxic GDs serum concentrations, we
      suggest that a ginger-supplemented diet might reduce OA symptoms.

PMID- 24039111
TI  - Drinking water purification by electrosynthesis of hydrogen peroxide in a power
      producing PEM fuel cell.
AB  - The industrial anthraquinone auto-oxidation process produces most of the world's
      supply of hydrogen peroxide. For applications that require small amounts of H2 O2
      or have economically difficult transportation means, an alternate, on-site H2 O2
      production method is needed. Advanced drinking water purification technologies
      use neutral-pH H2 O2 in combination with UV treatment to reach the desired water
      purity targets. To produce neutral H2 O2 on-site and on-demand for drinking water
      purification, the electroreduction of oxygen at the cathode of a proton exchange
      membrane (PEM) fuel cell operated in either electrolysis (power consuming) or
      fuel cell (power generating) mode could be a possible solution. The work
      presented here focuses on the H2 /O2 fuel cell mode to produce H2 O2 . The fuel
      cell reactor is operated with a continuous flow of carrier water through the
      cathode to remove the product H2 O2 . The impact of the cobalt-carbon composite
      cathode catalyst loading, Teflon content in the cathode gas diffusion layer, and
      cathode carrier water flowrate on the production of H2 O2 are examined. H2 O2
      production rates of up to 200 MUmol h(-1)  cmgeometric (-2) are achieved using a
      continuous flow of carrier water operating at 30 % current efficiency. Operation
      times of more than 24 h have shown consistent H2 O2 and power production, with no
      degradation of the cobalt catalyst. 

PMID- 24039112
TI  - Improved ultra-performance liquid chromatography with electrospray ionization
      quadrupole-time-of-flight high-definition mass spectrometry method for the rapid
      analysis of the chemical constituents of a typical medical formula: Liuwei
      Dihuang Wan.
AB  - Liuwei Dihuang Wan (LDW), a classic Chinese medicinal formula, has been used to
      improve or restore declined functions related to aging and geriatric diseases,
      such as impaired mobility, vision, hearing, cognition, and memory. It has
      attracted increasing attention as one of the most popular and valuable herbal
      medicines. However, the systematic analysis of the chemical constituents of LDW
      is difficult and thus has not been well established. In this paper, a rapid,
      sensitive, and reliable ultra-performance LC with ESI quadrupole TOF high
      definition MS method with automated MetaboLynx analysis in positive and negative
      ion mode was established to characterize the chemical constituents of LDW. The
      analysis was performed on a Waters UPLCTM HSS T3 using a gradient elution system.
      MS/MS fragmentation behavior was proposed for aiding the structural
      identification of the components. Under the optimized conditions, a total of 50
      peaks were tentatively characterized by comparing the retention time and MS data.
      It is concluded that a rapid and robust platform based on ultra-performance LC
      with ESI quadrupole TOF high-definition MS has been successfully developed for
      globally identifying multiple constituents of traditional Chinese medicine
      prescriptions. This is the first report on the systematic analysis of the
      chemical constituents of LDW. 

PMID- 24039113
TI  - Clinical and neurocognitive characterization of a family with a novel MED12 gene
      frameshift mutation.
AB  - FG syndrome, Lujan syndrome, and Ohdo syndrome, the Maat-Kievit-Brunner type,
      have been described as distinct syndromes with overlapping non-specific features
      and different missense mutations of the MED12 gene have been reported in all of
      them. We report a family including 10 males and 1 female affected with profound
      non-specific intellectual disability (ID) which was linked to a 30-cM region
      extending from Xp11.21 (ALAS2) to Xq22.3 (COL4A5). Parallel sequencing of all X
      chromosome exons identified a frameshift mutation (c.5898dupC) of MED12. Mutated
      mRNA was not affected by non-sense mediated RNA decay and induced an additional
      abnormal isoform due to activation of cryptic splice-sites in exon 41. Dysmorphic
      features common to most affected males were long narrow face, high forehead, flat
      malar area, high nasal bridge, and short philtrum. Language was absent or very
      limited. Most patients had a friendly personality. Cognitive impairment, varying
      from borderline to profound ID was similarly observed in seven heterozygous
      females. There was no correlation between cognitive function and X-chromosome
      inactivation profiles in blood cells. The severe degree of ID in male patients,
      as well as variable cognitive impairment in heterozygous females suggests that
      the duplication observed in the present family may have a more severe effect on
      MED12 function than missense mutations. In a cognitively impaired male from this
      family, who also presented with tall stature and dysmorphism and did not have the
      MED12 mutation, a 600-kb duplication at 17p13.3 including the YWHAE gene, was
      found in a mosaic state.

PMID- 24039114
TI  - Concepts and their dynamics: a quantum-theoretic modeling of human thought.
AB  - We analyze different aspects of our quantum modeling approach of human concepts
      and, more specifically, focus on the quantum effects of contextuality,
      interference, entanglement, and emergence, illustrating how each of them makes
      its appearance in specific situations of the dynamics of human concepts and their
      combinations. We point out the relation of our approach, which is based on an
      ontology of a concept as an entity in a state changing under influence of a
      context, with the main traditional concept theories, that is, prototype theory,
      exemplar theory, and theory theory. We ponder about the question why quantum
      theory performs so well in its modeling of human concepts, and we shed light on
      this question by analyzing the role of complex amplitudes, showing how they allow
      to describe interference in the statistics of measurement outcomes, while in the
      traditional theories statistics of outcomes originates in classical probability
      weights, without the possibility of interference. The relevance of complex
      numbers, the appearance of entanglement, and the role of Fock space in explaining
      contextual emergence, all as unique features of the quantum modeling, are
      explicitly revealed in this article by analyzing human concepts and their
      dynamics. 

PMID- 24039115
TI  - Remarkable biomimetic chemoselective aerobic oxidation of flavano-ellagitannins
      found in oak-aged wine.
AB  - Under the auspices of Bacchus! Acutissimins, natural flavano-ellagitannins, occur
      in oak-aged wine as a result of a diastereoselective condensation reaction of the
      flavan-3-ol catechin, a component of grapes, with the C-glucosidic ellagitannin
      vescalagin, found in oak. The acutissimins are further converted into natural
      mongolicains and analogues of camelliatannin G in a remarkably chemoselective
      fashion by simple aerobic oxidation. 

PMID- 24039116
TI  - Transcatheter treatment of iatrogenic brachiocephalic-jugular arteriovenous
      fistula and aortopulmonary artery fistula: a case report.
AB  - Iatrogenic arteriovenous fistula is not a common complication of central venous
      catheterization. Duct occluder devices have been developed for patent ductus
      arteriosus occlusions but they may be used for arteriovenous fistula closures. We
      report a case of iatrogenic brachiocephalic-jugular and aortopulmonary artery
      fistulas after central venous catheter insertion. The fistulas were successfully
      managed with duct occluder devices. Due to increasing number of central venous
      catheterizations, physicians should be aware of this uncommon complication.
      Transcatheter closing of brachiocephalic-jugular and aortopulmonary artery
      fistulas by duct occluder devices seems to be a safe and feasible form of
      treatment.

PMID- 24039117
TI  - Kinetically limited CO adsorption: spill-over as a highly effective adsorption
      pathway on bimetallic surfaces.
AB  - We demonstrate that the (local) adsorbed carbon monoxide, COad , coverage on the
      Pt-free areas of bimetallic Pt/Ru(0001) surfaces (a Ru(0001) substrate partly
      covered by Pt monolayer islands) can be increased to ~0.80 monolayers (ML), well
      above the established saturation COad coverage of 0.68 ML, even under ultrahigh
      vacuum conditions by using spill-over of CO adsorbed on the Pt islands to the Ru
      areas as an highly effective adsorption channel. The apparent COad saturation
      coverage of 0.68 ML on pure Ru(0001) is identified as due to kinetic limitations,
      hindering further uptake from the gas phase, rather than being caused by
      thermodynamic reasons. This spill-over mechanism is proposed to be a general
      phenomenon for adsorption on bimetallic surfaces. 

PMID- 24039118
TI  - High-temperature-stable and regenerable catalysts: platinum nanoparticles in
      aligned mesoporous silica wells.
AB  - We report the synthesis, structural characterization, thermal stability study,
      and regeneration of nanostructured catalysts made of 2.9 nm Pt nanoparticles
      sandwiched between a 180 nm SiO2 core and a mesoporous SiO2 shell. The SiO2 shell
      consists of 2.5 nm channels that are aligned perpendicular to the surface of the
      SiO2 core. The nanostructure mimics Pt nanoparticles that sit in mesoporous SiO2
      wells (Pt@MSWs). By using synchrotron-based small-angle X-ray scattering, we were
      able to prove the ordered structure of the aligned mesoporous shell. By using
      high-temperature cyclohexane dehydrogenation as a model reaction, we found that
      the Pt@MSWs of different well depths showed stable activity at 500  degrees C
      after the induction period. Conversely, a control catalyst, SiO2 -sphere
      supported Pt nanoparticles without a mesoporous SiO2 shell (Pt/SiO2 ), was
      deactivated. We deliberately deactivated the Pt@MSWs catalyst with a 50 nm deep
      well by using carbon deposition induced by a low H2 /cyclohexane ratio. The
      deactivated Pt@MSWs catalyst was regenerated by calcination at 500  degrees C
      with 20 % O2 balanced with He. After the regeneration treatments, the activity of
      the Pt@MSWs catalyst was fully restored. Our results suggest that the
      nanostructured catalysts-Pt nanoparticles confined inside mesoporous SiO2 wells
      are stable and regenerable for treatments and reactions that require high
      temperatures.

PMID- 24039119
TI  - Exhaled nitric oxide in childhood allergic asthma management: a randomised
      controlled trial.
AB  - OBJECTIVE: We investigated the potential yield of incorporating fractional
      exhaled nitric oxide (FeNO) measurements in childhood allergic asthma management.
      METHODS: Ninety-nine children with persistent allergic asthma were included in
      this multicentre, single-blind, randomized controlled trial. Treatment was based
      on the Global Initiative for Asthma (GINA) guidelines. In the FeNO group, asthma
      management was also guided by FeNO measurements. Health outcomes were evaluated
      over a 52-week timeframe. RESULTS: Fewer asthma exacerbations were registered in
      the FeNO group. 24% of the children in the FeNO group experienced one or more
      exacerbations per year, compared with 48% in the clinical group (P = 0.017). The
      proportion of symptom-free days did not differ between groups. In the FeNO group,
      more months of leukotriene receptor antagonist use (median (interquartile range))
      were observed: 12 (9-12) months, compared with 9 (3-12) months in the clinical
      group (P = 0.019). Next, the evolution of inhaled corticosteroid doses between
      visits 1 and 5 (median change (interquartile range)) showed a significant
      increase of +100 ug (0, +400) in the FeNO group and a change of 0 ug (-200, +80)
      in the clinical group (P = 0.016). CONCLUSIONS: FeNO measurements in childhood
      asthma management did not improve the proportion of symptom-free days, but did
      result in fewer asthma exacerbations associated with an increased leukotriene
      receptor antagonist use and an augmentation of the inhaled corticosteroid doses.

PMID- 24039121
TI  - Pitfalls of using administrative data sets to describe clinical outcomes in
      sickle cell disease.
AB  - BACKGROUND: Administrative data sets are increasingly being used to describe
      clinical care in sickle cell disease (SCD). We recently used such an
      administrative database to look at the frequency of acute chest syndrome (ACS)
      and the use of transfusion to treat this syndrome in California patients from
      2005 to 2010. Our results revealed a surprisingly low rate of transfusion for
      this life-threatening situation. PROCEDURE: To validate these results, we
      compared California OSPHD (Office of Statewide Health Planning and Development)
      administrative data with medical record review of patients diagnosed with ACS
      identified by two pediatric and one adult hospital databases during 2009-2010.
      RESULTS: ACS or a related pulmonary process accounted for one-fifth of the
      inpatient hospital discharges associated with the diagnosis of SCD between 2005
      and 2010. Only 47% of those discharges were associated with a transfusion.
      However, chart reviews found that hospital databases over-reported visits for
      ACS. OSHPD underreported transfusions compared to hospital data. The net effect
      was a markedly higher true rate of transfusion (40.7% vs. 70.2%). CONCLUSIONS:
      These results point out the difficulties in using this administrative data base
      to describe clinical care for ACS given the variation in clinician recognition of
      this entity. OSPHD is widely used to inform health care policy in California and
      contributes to national databases. Our study suggests that using this
      administrative database to assess clinical care for SCD may lead to inaccurate
      assumptions about quality of care for SCD patients in California. Future studies
      on health services in SCD may require a different methodology.

PMID- 24039120
TI  - Mathematical modeling of postmenopausal osteoporosis and its treatment by the
      anti-catabolic drug denosumab.
AB  - Denosumab, a fully human monoclonal antibody, has been approved for the treatment
      of postmenopausal osteoporosis. The therapeutic effect of denosumab rests on its
      ability to inhibit osteoclast differentiation. Here, we present a computational
      approach on the basis of coupling a pharmacokinetics model of denosumab with a
      pharmacodynamics model for quantifying the effect of denosumab on bone
      remodeling. The pharmacodynamics model comprises an integrated systems biology
      continuum micromechanics approach, including a bone cell population model,
      considering the governing biochemical factors of bone remodeling (including the
      action of denosumab), and a multiscale micromechanics-based bone mechanics model,
      for implementing the mechanobiology of bone remodeling in our model. Numerical
      studies of postmenopausal osteoporosis show that denosumab suppresses osteoclast
      differentiation, thus strongly curtailing bone resorption. Simulation results
      also suggest that denosumab may trigger a short-term bone volume gain, which is,
      however, followed by constant or decreasing bone volume. This evolution is
      accompanied by a dramatic decrease of the bone turnover rate by more than one
      order of magnitude. The latter proposes dominant occurrence of secondary
      mineralization (which is not anymore impeded through cellular activity), leading
      to higher mineral concentration per bone volume. This explains the overall higher
      bone mineral density observed in denosumab-related clinical studies.

PMID- 24039122
TI  - Enhanced detection of high-mass proteins by using an active pixel detector.
AB  - Flying high: Application of an active pixel detector with high charge sensitivity
      to a linear time-of-flight mass spectrometer results in enhanced detection of
      high-mass proteins (such as Immunoglobulin G; IgG) using a conventional
      microchannel plate detection system. This technique thus provides a means to
      extend the mass range of such detectors as well as allowing direct visualization
      of mass-dependent ion-focusing phenomena. 

PMID- 24039123
TI  - Imaging of blast injuries to the lower extremities sustained in the Boston
      marathon bombing.

PMID- 24039124
TI  - Gastric bypass after liver transplantation.
AB  - Few data are available for assessing the outcomes of bariatric surgery for
      patients who have undergone orthotopic liver transplantation (OLT). The
      University of Minnesota bariatric surgery database and transplant registry were
      retrospectively reviewed to identify patients who had undergone OLT and then open
      Roux-en-Y gastric bypass (RYGB) surgery between 2001 and 2009. Comorbidity
      appropriate laboratory values, body mass indices (BMIs), histopathology reports,
      and immunosuppressive regimens were collected. Seven patients were identified
      with a mean age of 55.4 +/- 8.64 years and a mean follow-up of 59.14 +/- 41.49
      months from the time of RYGB. The mean time between OLT and RYGB was 26.57 +/-
      8.12 months. The liver disease etiologies were hepatitis C (n = 4), jejunoileal
      bypass surgery (n = 1), hemangioendothelioma (n = 1), and alcoholic cirrhosis (n
      = 1). There were 2 deaths for patients with hepatitis C 6 and 9 months after
      bariatric surgery due to multiple-organ dysfunction syndrome and metastatic
      esophageal squamous carcinoma, respectively. One patient with hepatitis C
      required a reversal of the RYGB because of malnutrition and an inability to
      tolerate oral intake. Four of the 7 patients had type 2 diabetes mellitus (T2DM),
      4 had hypertension, and 6 patients had dyslipidemia. All patients were on
      immunosuppressive medications, but only 4 were on corticosteroids. Glycemic
      control was improved in all surviving patients with T2DM. The mean BMI was 34.27
      +/- 5.51 kg/m(2) before OLT and 44.34 +/- 6.08 kg/m(2) before RYGB; it declined
      to 26.47 +/- 5.53 kg/m(2) after RYGB. In conclusion, in this case series of
      patients undergoing RYGB after OLT, we observed therapeutic weight loss, improved
      glycemic control, and improved high-density lipoprotein levels in the presence of
      continued dyslipidemia. RYGB may have contributed to the death of 1 patient due
      to multiple-organ dysfunction syndrome.

PMID- 24039125
TI  - Non-immune hydrops fetalis: A prospective study of 53 cases.
AB  - Non-immune hydrops fetalis (NIHF) is a symptom caused by a heterogeneous group of
      conditions. Diagnostic investigations may constitute a real challenge. This study
      aimed to evaluate prospectively and systematically a series of NIHF cases using a
      research protocol expanded for studying inborn errors of metabolism (IEM) during
      2 years-2010 and 2011. We also reviewed the frequency of IEM among the NIHF
      reported in literature. A clinical or etiopathogenic diagnosis was reached in 46
      (86.8%) of the 53 studied cases. The main diagnostic groups were chromosomal
      anomalies (28.3%), syndromic (18.9%), isolated cardiovascular anomaly (7.5%) and
      congenital infection (7.5%). Metabolic causes were found in 5.7%, all lysosomal
      storage disorders (LSD). In seven (13.2%), no diagnosis was found in part because
      of incomplete evaluation. The hydrops was identified prenatally in 90.5% of
      cases. In 5.7% a spontaneous and complete resolution of the hydrops occurred
      during pregnancy. Overall mortality was 75.5%. The IEM frequency in the present
      study (5.7%) was higher than that usually reported. We suggest performing studies
      directed to IEMs if the more common causes are excluded.

PMID- 24039126
TI  - Differential methylation of the micro-RNA 7b gene targets postnatal maturation of
      murine neuronal Mecp2 gene expression.
AB  - DNA methylation and microRNAs (miRNAs) play crucial roles in maturation of
      postnatal mouse neurons. Aberrant DNA methylation and/or altered miRNA expression
      cause postnatal neurodevelopmental disorders. In general, DNA methylation in the
      5'-flanking region suppresses gene expression through recruitment of methyl-CpG
      binding domain proteins (MBPs) to the cytosine residues of CpG dinucleotides. X
      linked MeCP2 (methyl-CpG binding protein 2), a member of MBPs, is a methylation
      associated transcriptional repressor with other functions in the central nervous
      system (CNS). miRNAs negatively regulate gene expression by targeting the 3'
      untranslated region (3'UTR). Some miRNA genes harboring or being embedded in CpG
      islands undergo methylation-mediated silencing. One such miRNA is miR-7b which is
      differentially expressed through stages of neurodevelopment. In our present
      study, we focused on a canonical CpG island located in the 5'-flanking region of
      the murine miR-7b gene. Hypermethylation of this CpG island down-regulates miR-7b
      while recruiting MeCP2 to the methylated CpG dinucleotides. Meanwhile, Mecp2, a
      target of miR-7b, was up-regulated due to lack of restrain exerted by miR-7b
      during maturation of postnatal (PN) mouse neurons between PN3 and PN14. Our
      results indicate that miR-7b is a direct downstream gene transcriptional target
      while also being a negative post-transcriptional regulator of Mecp2 expression.
      We speculate that this bidirectional feed-back autoregulatory function of miR-7b
      and Mecp2 while linking DNA methylation and miRNA action maintains the
      homeostatic control of gene expression necessary during postnatal maturation of
      mammalian neurons.

PMID- 24039128
TI  - Differential hepatic GSTA2 expression of arylalkyl isothiocyanates in vivo and in
      vitro: the molecular mechanism of gene induction by phenethyl isothiocyanate.
AB  - SCOPE: Naturally occurring isothiocyanates (ITCs) have been investigated for
      their chemopreventive actions. However, limited studies have determined the
      potential for regulation of hepatic glutathione S-transferase A2 (GSTA2) by
      arylalkyl or alkyl ITCs. METHODS AND RESULTS: The present study was designed to
      investigate the effects of ITCs on GSTA2 expression and upstream signaling
      analyzed by Northern blotting, RT-PCR, immunoblotting, and promoter-luciferase
      assay. A single dose of ethyl isothiocyanate and phenethyl isothiocyanate (PEITC)
      enhanced GSTA2 mRNA levels in rats. The three consecutive injections of arylalkyl
      ITCs resulted in the gene induction. PEITC was the most potent and sustained
      inducer of GSTA2 in vivo. PEITC induced GSTA2 mRNA and protein expression in
      H4IIE cells. PEITC increased the levels of nuclear factor erythroid 2 related
      factor 2 and CCAAT/enhancer binding protein beta (C/EBPbeta). The cells
      transfected with a pGL-DeltaARE or pGL-DeltaC/EBP-deleted promoter construct
      failed to increase GSTA2 promoter activity by PEITC. These effects of PEITC were
      downstream of multiple cellular signaling, including phosphoinositide 3-kinase
      (PI3K), c-jun N-terminal kinase (JNK), and/or protein kinase A (PKA). CONCLUSION:
      These results demonstrated that PEITC is the most efficacious of the arylalkyl
      ITCs for the induction of GSTA2 in vivo and in vitro, and that transactivation of
      C/EBP and nuclear factor erythroid 2 related factor 2 downstream of multiple
      signaling pathways is involved in this induction.

PMID- 24039127
TI  - Antibacterial property expressed by a novel calcium phosphate glass.
AB  - We have developed a calcium phosphate glass (CPG) doped with Zn(2+) or F(-) or
      combined Zn(2+) and F(-) ions, which are naturally found in the human body and
      play a dual role in bone formation and antibacterial activity. Previously, we
      have demonstrated that this family of CPGs has superior osteoconductive and
      resorbable properties in vivo. This study aimed to investigate the antibacterial
      property of CPGs incorporating Zn(2+) and/or F(-) . We used Streptococcus mutans
      as a model organism because it is one of the major human oral pathogens and an
      early colonizer, and it has been associated with several oral infections, such as
      dental caries, periodontitis, and peri-implantitis. CPGs of 0.01 and 0.05 g were
      incubated with S. mutans for 0, 2, 4, and 6 h. Serial dilutions were plated in
      triplicate and colony forming units were determined. The antimicrobial effect of
      CPG incorporating Zn(2+) or F(-) was greater than CPG incorporating both these
      ions. CPG without doping produced a moderate antimicrobial effect. This family of
      CPGs, previously shown to promote new bone formation in vivo, is demonstrated to
      have superior bactericidal properties.

PMID- 24039129
TI  - Stabilizing the imidazolium cation in hydroxide-exchange membranes for fuel
      cells.
AB  - Stable and able: The hydroxide-conducting cationic functional group used in the
      hydroxide-exchange membranes of fuel cells is key to controlling chemical
      stability and solubility. A new imidazolium cation, 1,4,5-trimethyl-2-(2,4,6
      trimethoxyphenyl)imidazolium, is designed to take advantage of both strong
      electron-donation properties and steric hindrance. Synergy between these two
      effects leads to an efficient hydroxide-exchange membrane, with increased
      alkaline stability and improved OH(-) conductivity. 

PMID- 24039131
TI  - Alkoxide activation of aminoboranes towards selective amination.
AB  - Piece of the (inter)action: The interaction of alkoxides with the sp(2) Bpin
      (pin=pinacol) moiety in aminoboranes forms the in situ Lewis acid-base adduct
      [RO(-) ->B(OR)2 ?N(R')2 ] which enables the amino moiety to react as a strong
      nucleophile with several electrophiles, thus providing amino alcohols, beta
      enamino esters, and beta-hydroxy amides in a direct and remarkably selective way.

PMID- 24039132
TI  - The influence of reactive side products in electrocatalytic reactions: methanol
      oxidation as case study.
AB  - The role and impact of follow-up processes involving reactive side products in an
      electrocatalytic reaction is demonstrated for the electrooxidation of methanol at
      a Pt electrode. By using combined in situ infrared spectroscopy and online mass
      spectrometry and employing isotope-labeling techniques, it is shown that even
      small amounts of the incomplete oxidation products formaldehyde and formic acid
      have pronounced effects on the reaction. 

PMID- 24039133
TI  - Effects of maternal exposure to imazalil on behavioral development in F1
      generation mice.
AB  - Female mice were exposed maternally to imazalil through diet to provide levels of
      0 (control), 0.0006, 0.0018, and 0.0054% during gestation and lactation periods,
      and selected reproductive and neurobehavioral parameters were measured in F1
      generation. There was no adverse effect of imazalil on litter size, litter
      weight, or sex ratio at birth. With respect to behavioral developmental
      parameters, surface righting on postnatal day 4 of male offspring was delayed
      significantly in a dose-related manner (p < 0.05). Regarding exploratory behavior
      in the F1 generation, movement time was significantly long (p = 0.0206) in the
      low-dose group of males at 8 weeks of age. Spontaneous behavior examination in
      males indicated that movement time increased but in females decreased in the low
      dose groups in the F1 generation. The dose levels of imazalil in the present
      study produced some adverse effects in neurobehavioral parameters in mice.

PMID- 24039134
TI  - Aryl biphenyl-3-ylmethylpiperazines as 5-HT7 receptor antagonists.
AB  - The 5-HT7 receptor (5-HT7 R) is a promising therapeutic target for the treatment
      of depression and neuropathic pain. The 5-HT7 R antagonist SB-269970 exhibited
      antidepressant-like activity, whereas systemic administration of the 5-HT7 R
      agonist AS-19 significantly inhibited mechanical hypersensitivity and thermal
      hyperalgesia. In our efforts to discover selective 5-HT7 R antagonists or
      agonists, aryl biphenyl-3-ylmethylpiperazines were designed, synthesized, and
      biologically evaluated against the 5-HT7 R. Among the synthesized compounds, 1
      ([2'-methoxy-(1,1'-biphenyl)-3-yl]methyl)-4-(2-methoxyphenyl)piperazine (28) was
      the best binder to the 5-HT7 R (pKi =7.83), and its antagonistic property was
      confirmed by functional assays. The selectivity profile of compound 28 was also
      recorded for the 5-HT7 R over other serotonin receptor subtypes, such as 5-HT1 R,
      5-HT2 R, 5-HT3 R, and 5-HT6 R. In a molecular modeling study, the 2-methoxyphenyl
      moiety attached to the piperazine ring of compound 28 was proposed to be
      essential for the antagonistic function. 

PMID- 24039135
TI  - Aldehyde-selective Wacker-type oxidation of unbiased alkenes enabled by a nitrite
      co-catalyst.
AB  - Breaking the rules: Reversal of the high Markovnikov selectivity of Wacker-type
      oxidations was accomplished using a nitrite co-catalyst. Unbiased aliphatic
      alkenes can be oxidized with high yield and aldehyde selectivity, and several
      functional groups are tolerated. (18) O-labeling experiments indicate that the
      aldehydic O atom is derived from the nitrite salt. 

PMID- 24039130
TI  - Antimicrobial peptides and gut microbiota in homeostasis and pathology.
AB  - We survive because we adapted to a world of microorganisms. All our epithelial
      surfaces participate in keeping up an effective barrier against microbes while
      not initiating ongoing inflammatory processes and risking collateral damage to
      the host. Major players in this scenario are antimicrobial peptides (AMPs). Such
      broad-spectrum innate antibiotics are in part produced by specialized cells but
      also widely sourced from all epithelia as well as circulating inflammatory cells.
      AMPs belong to an ancient defense system found in all organisms and participated
      in a preservative co-evolution with a complex microbiome. Particularly
      interesting interactions between host barrier and microbiota can be found in the
      gut. The intestinal cell lining not only has to maintain a tightly regulated
      homeostasis during its high-throughput regeneration, but also a balanced
      relationship towards an extreme number of mutualistic or commensal inhabitants.
      Recent research suggests that advancing our understanding of the circumstances of
      such balanced and sometimes imbalanced interactions between gut microbiota and
      host AMPs should have therapeutic implications for different intestinal
      disorders. 

PMID- 24039136
TI  - Prenatal inflammatory risk factors for development of bronchopulmonary dysplasia.
AB  - BACKGROUND: Bronchopulmonary dysplasia (BPD) is a serious, chronic lung disease
      affecting preterm infants. OBJECTIVE: To identify prenatal risk factors for BPD,
      focusing on inflammation. METHODS: Observational cohort study including 106,339
      preterm infants, live born before gestational week 37 + 0, from 1988 to 2009 in
      Sweden. A total of 2,115 infants were diagnosed with BPD, of which 1,393 were
      born extremely preterm, before gestational week 28 + 0. Information on risk
      factors was obtained from national health registers and included maternal chronic
      inflammatory diseases, pregnancy related diseases, and drugs related to treatment
      of inflammation or infection during pregnancy. Adjusted odds ratios (OR) were
      calculated in multivariable logistic regression models and are presented with 95%
      confidence intervals [95% CI]. RESULTS: Preeclampsia was the strongest risk
      factor for BPD [adjusted OR 2.04, 95% CI 1.83, 2.29]. For extremely preterm
      infants the adjusted OR was 1.33 [95% CI 1.08, 1.64]. Chorioamnionitis was
      associated with an increased risk of BPD, but only when including all infants in
      the analyses [OR 1.33, 95% CI 1.19, 1.48]. No apparent associations were found
      between maternal chronic inflammatory disease or use of anti-inflammatory drugs
      and the risk of BPD. Maternal diabetes mellitus, gestational diabetes and
      maternal use of antibiotics were associated with reduced risks of BPD.
      CONCLUSION: Preeclampsia related disorders increased the risk and maternal
      diabetes mellitus and gestational diabetes reduced the risk for BPD. As
      angiogenic factors play a role in preeclampsia and diabetes our findings suggest
      that an impaired angiogenesis may contribute to BPD development.

PMID- 24039137
TI  - Simultaneous derivatization and air-assisted liquid-liquid microextraction of
      some parabens in personal care products and their determination by GC with flame
      ionization detection.
AB  - A simultaneous derivatization/air-assisted liquid-liquid microextraction
      technique has been developed for the sample pretreatment of some parabens in
      aqueous samples. The analytes were derivatized and extracted simultaneously by a
      fast reaction/extraction with butylchloroformate (derivatization agent/extraction
      solvent) from the aqueous samples and then analyzed by GC with flame ionization
      detection. The effect of catalyst type and volume, derivatization
      agent/extraction solvent volume, ionic strength of aqueous solution, pH, numbers
      of extraction, aqueous sample volume, etc. on the method efficiency was
      investigated. Calibration graphs were linear in the range of 2-5000 MUg/L with
      squared correlation coefficients >0.990. Enhancement factors and enrichment
      factors ranged from 1535 to 1941 and 268 to 343, respectively. Detection limits
      were obtained in the range of 0.41-0.62 MUg/L. The RSDs for the extraction and
      determination of 250 MUg/L of each paraben were <4.9% (n = 6). In this method,
      the derivatization agent and extraction solvent were the same and there is no
      need for a dispersive solvent, which is common in a traditional dispersive liquid
      liquid microextraction technique. Furthermore, the sample preparation time is
      very short.

PMID- 24039138
TI  - Helex device closure of multiple atrial septal defects.
AB  - OBJECTIVES: To describe the effectiveness of the Helex Septal Occluder (HSO) to
      close multiple atrial septal defects (mASDs). Background : Limited information is
      available describing closure of mASDs with the HSO. METHODS: A total of 28
      patients who underwent closure of mASDs with the HSO were identified by
      retrospective review of our catheterization database between 2001 and 2012.
      Procedural details and follow up information were collected. RESULTS: Median age
      was 19.2 years, median weight 48 kg, with 10 (36%) patients weighing <25 kg.
      Indication for closure was RV enlargement (RVE) in all patients and additionally
      neurologic events occurred in 3/28 (11%). Median stop-flow diameter for the
      largest ASD was 14 (4-23) mm. One HSO was implanted in 21/28 (75%), 2 in 6/28
      (21%), and 3 in 1/28 (4%). One embolization and one transient arrhythmia occurred
      with no sequelae. Immediate residual shunt was absent in 5/28 (18%), trivial in
      15/28 (54%), small in 6/28 (21%), and moderate in 2/28 (7%). Of the 25 patients
      with >=6 months follow-up (median 53 months), residual shunt was absent in 13/25
      (52%), trivial in 5/25 (20%), and small in 7/25 (28%). RVE resolved in all but
      one patient with no other associated lesions and >=6 months of follow-up. No
      patient with prior neurological event had recurrence at last follow-up.
      CONCLUSIONS: We conclude that closure of mASDs with >=1 HSO is effective with a
      low complication rate. The ability of HSO devices to overlap or sandwich each
      other may facilitate safe implantation of multiple devices in smaller patients.

PMID- 24039139
TI  - Factors relating to pregnancy and birth and the risk of childhood brain tumors:
      results from an Australian case-control study.
AB  - BACKGROUND: Childhood brain tumors (CBT) are the leading cause of cancer death in
      children, yet their causes are largely known. This study investigated the
      association between maternal and birth characteristics and risk of CBT.
      PROCEDURES: Cases families were recruited from all 10 Australian pediatric
      oncology centers between 2005 and 2010. Control families were recruited via
      random-digit dialing, frequency matched to cases on the basis of child's age,
      sex, and State of residence. Maternal and birth characteristics of children were
      ascertained by questionnaires. Odds ratios (ORs) and 95% confidence intervals
      (CI) were estimated using unconditional logistic regression, adjusting for
      relevant confounders. RESULTS: For this analysis, data on 319 case children and
      1,079 control children were available. No association was found between risk of
      CBT and birth weight, fetal growth, birth order, gestational age, or maternal
      body mass index. The ORs for inadequate and excessive maternal gestational weight
      gain (GWG) (Institute of Medicine 2009 guidelines) were 1.8 (95% CI 1.2-2.6) and
      1.4 (95% CI 1.0-2.1), respectively; similar findings for GWG were seen across
      categories of child's age, fetal growth, maternal body mass index and height,
      maternal smoking, and parental education. Risk of low grade glioma appeared
      increased with preterm birth (OR 1.6 (95% CI 0.8-3.1) and admission to neonatal
      intensive care (NICU) for >2 days (OR 1.7, 95% CI 0.9-3.6). CONCLUSION: We found
      little evidence of associations between risk of CBT and most birth
      characteristics. The associations we observed with GWG, prematurity and NICU
      admission require corroboration in other studies.

PMID- 24039140
TI  - Validating posttransplant hepatocellular carcinoma recurrence data in the United
      Network for Organ Sharing database.
AB  - The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ
      Sharing (UNOS) database is the most comprehensive collection of liver
      transplantation data, but the quality of these data with respect to
      hepatocellular carcinoma (HCC) recurrence has not been well assessed. In this
      study, we compared observed HCC recurrence rates in the UNOS database to expected
      rates calculated with a hierarchical model for recurrence adjusted for recipient
      and tumor characteristics. We used the UNOS Standard Transplant Analysis and
      Research data set for adult transplant patients with an initial exception for an
      HCC diagnosis granted between January 1, 2006 and September 30, 2010 who
      underwent transplantation within the same time window. We developed a risk
      adjusted Poisson model with patients as the unit of analysis, random effects for
      transplant centers, and years of follow-up as an offset to predict expected
      recurrences for each center. To further investigate the possibility of
      underreporting, we imputed expected recurrences for non-HCC deaths. In all, 5034
      HCC liver transplant recipients were identified, and 6.8% experienced recurrence
      at a median of 1 year after transplantation. The covariate-adjusted shrinkage
      estimates of the observed/expected HCC recurrence ratios by transplant center
      ranged from 0.6 to 1.76 (median = 0.97). The 95% confidence intervals for the
      shrinkage ratios included unity for every center, and this indicated that none
      could be unambiguously identified as having lower or higher than expected HCC
      recurrence rates. Imputing outcomes for patients potentially experiencing
      unreported recurrence changed the center-specific shrinkage ratios to 0.72 to
      1.39 (median = 0.98), with no centers having a shrinkage ratio significantly
      different from 1. The observed HCC recurrence rate was not significantly lower
      than the expected rate at any center, and this suggests that no systematic
      underreporting has occurred. This study validates the OPTN HCC recurrence data
      and supports their potential for further analysis.

PMID- 24039141
TI  - Differentiation of embryonic stem cells to cardiomyocytes on electrospun
      nanofibrous substrates.
AB  - The potential of pluripotent embryonic stem cells (ESCs) isolated from the inner
      mass of blastocysts are investigated for its ability to differentiate on
      biocompatible electrospun nanofibers, for regeneration of the myocardially
      infracted heart. Nanostructured poly(d,l-lactide-co-glycolide)/collagen
      (PLGA/Col) scaffolds with fiber diameters in the range of 300 +/- 65 nm, was
      fabricated by electrospinning to mimic the extracellular matrix of the native
      tissue. During the culture of embryoid bodies outgrowth on the scaffolds, and
      further differentiation of ESCs to cardiomyocytes, the PLGA/Col nanofibers was
      found better than that of the electrospun PLGA nanofibers, where a better
      interaction and growth of ESC differentiated cardiomyocytes was observed on the
      composite scaffolds. The phenotypical characteristics of ESC-derived
      cardiomyocytes and molecular protein expression were carried out by scanning
      electron microscopy and immunocytochemistry, respectively. Our studies highlight
      the significance of a suitable material, its architecture, and cell-biomaterial
      interactions that is essential at a nanoscale level signifying the application of
      a bioengineered cardiac graft for stem cell differentiation and transplantation,
      which could be an intriguing strategy for cardiac regeneration.

PMID- 24039142
TI  - Infrared sensitizers in titania-based dye-sensitized solar cells using a
      dimethylferrocene electrolyte.
AB  - Vide infra: Two boron-dipyrromethene (BODIPY)-type infrared sensitizers are
      investigated for use in titania-based dye-sensitized solar cells (DSCs). The DSCs
      use a solution of dimethylferrocene (Me2 Fc) in nitromethane as electrolyte. The
      titania conduction band edge is fine-tuned by adding lithium ions from LiTFSI,
      while the choice of dimethylferrocene as redox shuttle provides the ideal driving
      force for dye regeneration, allowing the BODIPY-based DSCs to reach unprecedented
      quantum efficiencies in the near-infrared. 

PMID- 24039143
TI  - Effects of changing physiologic conditions on the in vivo quantification of
      hemodynamic variables in cerebral aneurysms treated with flow diverting devices.
AB  - Quantifying the hemodynamic environment within aneurysms and its change after
      deployment of flow diverting devices is important to assess the device efficacy
      and understand their long-term effects. The purpose of this study was to estimate
      deviations in the quantification of the relative change of hemodynamic variables
      during flow diversion treatment of cerebral aneurysms due to changing physiologic
      flow conditions. Computational fluid dynamics calculations were carried out on
      three patient-specific geometries. Three flow diverters were virtually implanted
      in each geometry and simulations were performed under five pulsatile flow
      conditions. Hemodynamic variables including aneurysm inflow rate, mean velocity,
      shear rate, and wall shear stress were quantified before and after stenting.
      Deviations in the relative change of these variables due to varying flow
      conditions were calculated. The results indicate that a change in the mean flow
      of the parent artery of approximately 30-50% can induce large deviations in the
      relative change of hemodynamic variables in the range of 30-80%. Thus,
      quantification of hemodynamic changes during flow diversion must be carried out
      carefully. Variations in the inflow conditions during the procedure may induce
      large deviations in the quantification of these changes.

PMID- 24039144
TI  - Origin of photocatalytic activity in continuous gas phase CO(2) reduction over
      Pt/TiO(2).
AB  - The dynamic nature of continuous photocatalytic reduction of gaseous CO2 in the
      presence of water vapor was studied by using Pt/TiO2 as catalyst under UV
      irradiation at 353 and 423 K in the absence of sacrificial electron donors. The
      reaction was studied with a good time resolution (order of seconds), to monitor
      product concentrations by means of mass spectrometry. Two distinct photocatalytic
      activities, namely steady-state and transient, were identified. The former is
      active at the lower temperature and only for H2 production, whereas the latter
      dominates for CH4 production. The transient activity was recovered during dark
      time (i.e., the light is off) in the reaction mixture, with the magnitude of
      recovery proportionally increasing with the duration of the dark time. Higher
      temperature was found to be more effective for the recovery. Furthermore,
      insights into deactivation and reactivation mechanisms are explained by in situ
      diffuse reflectance infrared Fourier transform spectroscopy study. 

PMID- 24039145
TI  - Homozygosity for a novel truncating mutation confirms TBX15 deficiency as the
      cause of Cousin syndrome.
AB  - Cousin syndrome, also called pelviscapular dysplasia (OMIM 260660), is
      characterized by short stature, craniofacial dysmorphism, and multiple skeletal
      anomalies. Following its description in two sibs in 1982, no new cases have been
      observed until the observation of two unrelated cases in 2008 who were homozygous
      for frameshift mutations in TBX15. We investigated an adult individual with short
      stature, a complex craniofacial dysmorphism, malformed and rotated ears, short
      neck, elbow contractures, hypoacusis, and hypoplasia of scapula and pelvis on
      radiographs. We identified homozygosity for a novel nonsense mutation (c.841C>T)
      in TBX15 predicted to cause a premature stop (p.Arg281*) with truncation of the
      protein. This observation confirms that Cousin syndrome is a consistent and
      clinically recognizable phenotype caused by loss of function of TBX15.

PMID- 24039146
TI  - Generation of spatially aligned collagen fiber networks through microtransfer
      molding.
AB  - The unique biomechanical properties of native tissue are governed by the
      organization and composition of integrated collagen and elastin networks. An
      approach for fabricating spatially aligned, fiber-reinforced composites with
      adjustable collagen fiber dimensions, layouts, and distribution within an elastin
      like protein matrix yielding a biocomposite with controllable mechanical
      responses is reported. Microtransfer molding is employed for the fabrication of
      hollow and solid collagen fibers with straight or crimped fiber geometries.
      Collagen fibers (width: 2-50 MUm, thickness: 300 nm to 3 MUm) exhibit a Young's
      modulus of 126 +/- 61 MPa and an ultimate tensile strength of 7 +/- 3.2 MPa. As
      fiber networks within composite structures, straight fiber layouts display
      orthotropic responses with Young's modulus ranging from 0.95 +/- 0.35 to 10.4 +/-
      0.5 MPa and tensile strength from 0.22 +/- 0.08 to 0.87 +/- 0.5 MPa with
      increasing fraction of collagen fibers (1-10%, v/v). In contrast, composites
      based on crimped fiber layouts exhibit strain-dependent stiffness with an
      increase in Young's modulus from 0.7 +/- 0.14 MPa to 3.15 +/- 0.49 MPa, at a
      specific transition strain. Through controlling the microstructure of engineered
      collagen fiber networks, a facile means is established to control macroscale
      mechanical responses of composite protein-based materials. 

PMID- 24039147
TI  - Dose-response plasma appearance of coffee chlorogenic and phenolic acids in
      adults.
AB  - SCOPE: Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even
      though coffee intake has been associated with some health benefits in
      epidemiological studies, the bioavailability of coffee phenolics is not fully
      understood. OBJECTIVE AND STUDY DESIGN: We performed a dose-response study
      measuring plasma bioavailability of phenolics after drinking three increasing,
      but still nutritionally relevant doses of instant pure soluble coffee. The study
      design was a one treatment (coffee) three-dose randomized cross-over design, with
      a washout period of 2 wks between visits. RESULTS: CGAs, phenolic acids, and late
      appearing metabolites all increased with increasing ingested dose. Hence, the sum
      of area under the curve was significantly higher for the medium to low dose, and
      high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well
      absorbed in their intact form, regardless of the dose. CGA and phenolic acids
      appeared rapidly in plasma, indicating an early absorption in the
      gastrointestinal tract. Late-appearing metabolites were the most abundant,
      regardless of the dose. CONCLUSION: This study confirmed previous findings about
      coffee bioavailability but also showed that coffee phenolics appear in a positive
      dose-response manner in plasma when drank at nutritionally relevant doses.

PMID- 24039148
TI  - A prospective, randomized, controlled study of NIPPV versus nCPAP in preterm and
      term infants with respiratory distress syndrome.
AB  - OBJECTIVE: To evaluate whether nasal intermittent positive pressure ventilation
      (NIPPV) compared with nasal continuous positive airway pressure (nCPAP) decreases
      the requirement for endotracheal ventilation in preterm and term infants with
      respiratory distress syndrome (RDS). METHODS: This was a single center,
      randomized, controlled trial. A total of 179 preterm and term infants with RDS
      were randomized to NIPPV (n = 88) or nCPAP (n = 91). The clinical data of
      enrolled infants including blood gas analysis, PaO2 /FiO2 ratio, incidence of
      intubation, and complications, if occurred, were recorded. The primary outcome
      was the need for endotracheal ventilation. The secondary outcome was the
      measurement of favorable outcome, which was defined as discharged without any
      respiratory support and feeding well and gaining weight. Analysis followed
      slightly modified intention to treat principle. RESULTS: Significantly less
      number of infants randomized to NIPPV group required intubation and mechanical
      ventilation compared with nCPAP group (11.4% vs. 20.9%, P < 0.05). A favorable
      outcome was more likely in infants randomized to NIPPV (93.2% vs. 84.6%, P <
      0.05). In subgroup analysis, NIPPV was associated with reduced need for
      intubation in preterm (9.9% vs. 19.2%) and term (17.6% vs. 27.8%) infants, but
      the difference was statistically significant only in preterm infants(P < 0.05).
      CONCLUSION: Treatment with NIPPV compared with nCPAP decreased the need for
      endotracheal ventilation and increased favorable outcome in preterm and term
      infants with RDS.

PMID- 24039149
TI  - Outcome of pediatric patients with acute myeloid leukemia (AML) and -5/5q-
      abnormalities from five pediatric AML treatment protocols: a report from the
      Children's Oncology Group.
AB  - BACKGROUND: Abnormalities of chromosome 5q (-5/5q-) are associated with poor
      prognosis in adults with acute myeloid leukemia (AML). However, there are no
      large studies on outcomes of children with -5/5q- AML. To determine the disease
      correlates of this group, we retrospectively analyzed cytogenetic data from five
      studies of childhood AML. PROCEDURE: Data from patients whose cytogenetic clones
      included -5/5q-, with the exception of those with acute promyelocytic leukemia or
      Down syndrome, were included. RESULTS: Of the 2,240 patients with cytogenetic
      data available, 26 (1.2%) had -5 or 5q-. A significant number of these patients
      were age 11-21 (61.5%, P = 0.031) and had M0 morphology compared with patients
      without -5/5q- (24.0% vs. 2.8%, P < 0.001). Twenty-two of the 26 patients had a
      complete remission (CR) response to induction chemotherapy. The 5-year overall
      survival (OS) from the time of diagnosis for the -5/5q- patients was
      significantly lower than for patients without -5/5q- (27 +/- 17% vs. 50 +/- 2%, P
      = 0.027). Similarly, from induction CR, patients with -5/5q- had significantly
      worse disease free survival, OS and relapse risk than those without this
      abnormality (27 +/- 19% vs. 46 +/- 2%, P = 0.035, 32 +/- 20% vs. 57 +/- 2%, P =
      0.025, 68 +/- 21% vs. 45 +/- 2%, P = 0.01, respectively). CONCLUSIONS: Pediatric
      patients with AML and -5/5q- had a very poor outcome. These findings support the
      need for new or novel therapies for these patients.

PMID- 24039150
TI  - X-ray structural analysis of tau-tubulin kinase 1 and its interactions with small
      molecular inhibitors.
AB  - Tau-tubulin kinase 1 (TTBK1) is a serine/threonine/tyrosine kinase that
      putatively phosphorylates residues including S422 in tau protein.
      Hyperphosphorylation of tau protein is the primary cause of tau pathology and
      neuronal death associated with Alzheimer's disease. A library of 12 truncation
      variants comprising the TTBK1 kinase domain was screened for expression in
      Escherichia coli and insect cells. One variant (residues 14-313) could be
      purified, but mass spectrometric analysis revealed extensive phosphorylation of
      the protein. Co-expression with lambda phosphatase in E. coli resulted in
      production of homogeneous, nonphosphorylated TTBK1. Binding of ATP and several
      compounds to TTBK1 was characterized by surface plasmon resonance. Crystal
      structures of TTBK1 in the unliganded form and in complex with ATP, and two high
      affinity ATP-competitive inhibitors, 3-[(6,7-dimethoxyquinazolin-4
      yl)amino]phenol (1) and methyl 2-bromo-5-(7H-pyrrolo[2,3-d]pyrimidin-4
      ylamino)benzoate (2), were elucidated. The structure revealed two clear basic
      patches near the ATP pocket providing an explanation of TTBK1 for phosphorylation
      primed substrates. Interestingly, compound 2 displayed slow binding kinetics to
      TTBK1, the structure of TTBK1 in complex with this compound revealed a
      reorganization of the L199-D200 peptide backbone conformation together with
      altered hydrogen bonding with compound 2. These conformational changes necessary
      for the binding of compound 2 are likely the basis of the slow kinetics. This
      first TTBK1 structure can assist the discovery of novel inhibitors for the
      treatment of Alzheimer's disease. 

PMID- 24039151
TI  - Capillary liquid chromatography fraction collection and postcolumn reaction using
      segmented flow microfluidics.
AB  - A challenge for capillary LC (cLC) is fraction collection and the manipulation of
      fractions from microscale columns. An emerging approach is the use of segmented
      flow or droplet technology to perform such tasks. In this work, a fraction
      collection and postcolumn reaction system based on segmented flow was developed
      for the gradient cLC of proteins. In the system, column effluent and immiscible
      oil are pumped into separate arms of a tee resulting in regular fractions of
      effluent segmented by oil. Fractions were generated at 1 Hz corresponding to 5 nL
      volumes. The fraction collection rate was high enough to generate over 30
      fractions per peak and preserve chromatographic resolution achieved for a five
      protein test mixture. The resulting fractions could be stored and subsequently
      derivatized for fluorescence detection by pumping them into a second tee where
      naphthalene dicarboxyaldehyde, a fluorogenic reagent, was pumped into a second
      arm and added to each fraction. Proteins were derivatized within the droplets
      enabling postcolumn fluorescence detection of the proteins. The experiments
      demonstrate that fraction collection from cLC by segmented flow can be extended
      to proteins. Further, they illustrate a potential workflow for protein analysis
      based on postcolumn derivatization for fluorescence detection. 

PMID- 24039152
TI  - Inverse problems in 1D hemodynamics on systemic networks: a sequential approach.
AB  - In this work, a sequential approach based on the unscented Kalman filter is
      applied to solve inverse problems in 1D hemodynamics, on a systemic network. For
      instance, the arterial stiffness is estimated by exploiting cross-sectional area
      and mean speed observations in several locations of the arteries. The results are
      compared with those ones obtained by estimating the pulse wave velocity and the
      Moens-Korteweg formula. In the last section, a perspective concerning the
      identification of the terminal models parameters and peripheral circulation
      (modeled by a Windkessel circuit) is presented.

PMID- 24039153
TI  - Electrocatalysis on shape-controlled titanium nitride nanocrystals for the oxygen
      reduction reaction.
AB  - The high price of platinum (Pt)-based cathode catalysts for the oxygen reduction
      reaction (ORR) have slowed down the practical application of fuel cells. Thanks
      to their low cost, and outstanding, stable catalytic properties, titanium
      nitrides (TiN) are among the most promising non-precious metal electrocatalysts
      for replacing Pt. However, the shape-activity relationships of TiN
      electrocatalysts have not been well-studied or understood up to now. In this
      work, by simply adjusting the shape of TiO2 precursor, we are able to tailor the
      morphology of the TiN catalysts from nanoparticles to nanotubes. We have
      synthetized uniform carbon-coated titanium nitride nanotubes (carbon-coated TiN
      NTs) through a nitridation reaction in NH3 flow using a TiO2 nanotubes/melamine
      mixture as precursor. The carbon-coated TiN NTs hybrids exhibit excellent
      electrocatalytic activity for the ORR, coupled with superior methanol tolerance
      and long-term stability in comparison to commercial Pt/C, through an efficient
      four-electron-dominant ORR process. Compared with nanoparticles, the one
      dimensional and hollow structure of the nanotubes result in greater diffusion of
      electrolyte and superior electrical conductivity, and contribute to the greatly
      improved electrocatalytic performance of the carbon-coated TiN NTs
      nanocomposites.

PMID- 24039154
TI  - Enhanced apoptotic effects of dihydroartemisinin-aggregated gelatin and
      hyaluronan nanoparticles on human lung cancer cells.
AB  - Recent studies suggest that dihydroartemisinin (DHA), a derivative of artemisinin
      isolated from the traditional Chinese herb Artemisia annua L., has anticancer
      properties. Due to poor water solubility, poor oral activity, and a short plasma
      half-life, large doses of DHA have to be injected to achieve the necessary
      bioavailability. This study examined increasing DHA bioavailability by
      encapsulating DHA within gelatin (GEL) or hyaluronan (HA) nanoparticles via an
      electrostatic field system. Observations from transmission electron microscopy
      show that DHA in GEL and HA nanoparticles formed GEL/DHA and HA/DHA aggregates
      that were approximately 30-40 nm in diameter. The entrapment efficiencies for DHA
      were approximately 13 and 35% for the GEL/DHA and HA/DHA aggregates,
      respectively. The proliferation of A549 cells was inhibited by the GEL/DHA and
      HA/DHA aggregates. Fluorescent annexin V-fluorescein isothiocyanate (FITC) and
      propidium iodide (PI) staining displayed low background staining with annexin V
      FITC or PI on DHA-untreated cells. In contrast, annexin V-FITC and PI stains
      dramatically increased when the cells were incubated with GEL/DHA and HA/DHA
      aggregates. These results suggest that DHA-aggregated GEL and HA nanoparticles
      exhibit higher anticancer proliferation activities than DHA alone in A549 cells
      most likely due to the greater aqueous dispersion after hydrophilic GEL or HA
      nanoparticles aggregation. These results demonstrate that DHA can aggregate with
      nanoparticles in an electrostatic field environment to form DHA nanosized
      aggregates.

PMID- 24039155
TI  - Adoptive immunotherapy with antigen-specific T cells during extracorporeal
      membrane oxygenation (ECMO) for adenovirus-related respiratory failure in a child
      given haploidentical stem cell transplantation.
AB  - We report on the successful infusion of human adenovirus (HAdV)-specific T cells
      in a child with congenital amegakaryocytic thrombocytopenia, given T-cell
      depleted hematopoietic stem cell transplantation (HSCT) from the HLA
      haploidentical mother during extracorporeal membrane oxygenation (ECMO) for
      severe HAdV-related respiratory failure. Donor-derived, interferon (IFN)-gamma
      secreting HAdV-specific T cells were enriched using the cytokine capture assay,
      after in vitro stimulation with overlapping peptides from the immunodominant
      HAdV5 hexon protein. Two weeks after T-cell transfer, viral load decreased and
      ECMO was discontinued. T-cell responses to HAdV antigens were documented after
      four weeks and were associated with viral clearance, immune reconstitution and
      clinical amelioration.

PMID- 24039156
TI  - Transcatheter patch closure of an atrial septal defect of sinus venosus type
      using the immediate release patch.
AB  - Following promising preclinical studies, we report our first clinical experience
      with transcatheter closure of an atrial septal defect of sinus venosus type in a
      65-year-old patient using the Immediate Release Patch.

PMID- 24039157
TI  - Microneedle electrodes toward an amperometric glucose-sensing smart patch.
AB  - Here, efforts toward the development of a microneedle-based glucose sensor or
      "smart patch" for intradermal glucose sensing are described. Metallic microneedle
      array electrodes, conducting polymers, and glucose oxidase form the sensor
      platform. This work represents the first steps toward the development of
      painless, transdermal-sensing devices for continuous glucose monitoring. 

PMID- 24039158
TI  - On-site cytopathology for endoscopic ultrasound-guided fine-needle aspiration of
      solid pancreatic masses: Is it time to make it standard of care?

PMID- 24039160
TI  - Reaffirmation of GAK, but not HLA-DRA, as a Parkinson's disease susceptibility
      gene in a Taiwanese population.
AB  - Recent genome-wide association studies of Parkinson's disease (PD) in Caucasian
      populations have identified two new susceptibility loci, GAK and HLA-DRA;
      however, only limited information exists regarding the involvement of these genes
      in PD risk in other ethnic groups. Here, we examined whether these genetic
      effects were consistent in a Taiwanese PD population. In a total 900
      participants, including 448 PD patients and 452 control subjects, we genotyped
      the rs11248051 and rs1564282 variants of GAK, and the rs3129882 variant of HLA
      DRA. Logistic regression analysis was used to test for associations between
      genotype and PD under an additive model, adjusting for age and gender. Subjects
      with CT/TT genotypes of GAK rs11248051 had a modestly increased association with
      PD compared to those with CC genotype (OR = 1.37; 95% CI = 1.09, 1.87; P = 0.03).
      Carriers and non-carriers exhibited indistinguishable phenotypes in regards to
      clinical presentation and onset age. We observed no association between PD risk
      and GAK rs1564282 or HLA-DRA rs3129882 variant. The different genetic effects
      between Taiwanese and Caucasian populations may come from differences in
      population structure and geographic region-specific genetic-environmental
      interactions. In conclusion, our results supported the association between the
      rs11248051 variant in GAK and PD risk in a Taiwanese population. Future
      functional studies of GAK in neuronal degeneration are warranted to unravel its
      role in the pathogenetic mechanism of PD.

PMID- 24039159
TI  - Genome-wide identification and functional analyses of microRNA signatures
      associated with cancer pain.
AB  - Cancer pain remains a major challenge and there is an urgent demand for the
      development of specific mechanism-based therapies. Various diseases are
      associated with unique signatures of expression of microRNAs (miRNAs), which
      reveal deep insights into disease pathology. Using a comprehensive approach
      combining genome-wide miRNA screening, molecular and in silico analyses with
      behavioural approaches in a clinically relevant model of metastatic bone-cancer
      pain in mice, we now show that tumour-induced conditions are associated with a
      marked dysregulation of 57 miRNAs in sensory neurons corresponding to tumour
      affected areas. By establishing protocols for interference with disease-induced
      miRNA dysregulation in peripheral sensory neurons in vivo, we functionally
      validate six dysregulated miRNAs as significant modulators of tumour-associated
      hypersensitivity. In silico analyses revealed that their predicted targets
      include key pain-related genes and we identified Clcn3, a gene encoding a
      chloride channel, as a key miRNA target in sensory neurons, which is functionally
      important in tumour-induced nociceptive hypersensitivity in vivo. Our results
      provide new insights into endogenous gene regulatory mechanisms in cancer pain
      and open up attractive and viable therapeutic options.

PMID- 24039161
TI  - Protective effect of a pomace olive oil concentrated in triterpenic acids in
      alterations related to hypertension in rats: mechanisms involved.
AB  - SCOPE: Despite the amount of information and research on the effects of virgin
      olive oil and its components in cardiovascular disease, little attention has been
      paid to the effects of pomace olive oil, an olive oil subproduct traditionally
      used in Spain. The aim of the present study was to evaluate the potential effects
      of a pomace olive oil concentrated in triterpenic acids (POCTA) on blood
      pressure, cardiac hemodynamics, and functional and molecular vascular alterations
      associated with hypertension in spontaneously hypertensive rats (SHR). METHODS
      AND RESULTS: The study showed that POCTA attenuated the increase of blood
      pressure in SHR. This effect was associated with an improvement in endothelium
      dependent relaxation, enhancement of vascular expression of endothelial nitric
      oxide synthase, and reduction of tumor necrosis factor alpha, transforming growth
      factor beta, and collagen I. Furthermore, POCTA improved cardiac hemodynamics
      (left ventricular systolic pressure and left ventricular end-diastolic pressure)
      and decreased relative kidney and lung weights. CONCLUSION: POCTA exerts
      antihypertensive effects together with vascular and hypertension target organ
      protection in SHR. Since interest in pomace olive oil has been low, the results
      of this study contribute to increasing awareness of its biological and
      nutritional values.

PMID- 24039162
TI  - Heterogeneous catalytic hydrogenation of biobased levulinic and succinic acids in
      aqueous solutions.
AB  - Supported noble-metal catalysts (Ru, Pd or Pt) and the corresponding Re-promoted
      catalysts exhibit a high activity for the hydrogenation of biobased carboxylic
      acids. Levulinic acid and succinic acid are converted into the lactones or the
      diols depending on the nature of the catalyst and the reaction conditions. The
      highest selectivity to 1,4-pentanediol of 82 % is achieved at 140  degrees C in
      the presence of the 1.9 % Ru-3.6 % Re/C catalyst. 

PMID- 24039163
TI  - Current treatment and outcome for childhood acute leukemia in Tanzania.
AB  - BACKGROUND: In order to understand the disparity in childhood leukemia survival
      in low-income countries (LICs) compared to high-income countries (HICs), we
      evaluated the resources available at Tanzania's national pediatric oncology ward,
      and clinical characteristics, disease course and outcomes of children diagnosed
      with acute leukemia from 2008 through 2010. PROCEDURES: A chart review and
      assessment of services was performed to assess childhood leukemia diagnoses,
      treatment, and outcomes in Tanzania at the Ocean Road Cancer Institute (ORCI)
      from January 1, 2008 to December 31, 2010. Results were compared to those from a
      2005 evaluation that showed only one of 20 children with leukemia surviving at 1
      year. RESULTS: During the study period, 106 patients presented with leukemia,
      including 81 patients with acute lymphoblastic leukemia (ALL) and 25 with acute
      myeloid leukemia (AML). Forty-nine of 58 (84%) patients with ALL, and six of 17
      (35%) with AML who received therapy and had complete data, achieved complete
      remission. Estimated 2-year event-free survival for all patients with ALL was
      33%; for AML it was 0%. Ten patients died prior to initiation of therapy, 19 died
      of toxicity, and eight abandoned therapy. CONCLUSIONS: Though leukemia survival
      in Tanzania remains far below that in HICs, survival rates for ALL have
      significantly improved in recent years due to standardization of treatment
      regimens and better staff, though AML outcome remains dismal. Ongoing
      improvements in pediatric leukemia outcomes will require strategies to improve
      awareness and early access to treatment coupled with improvements in diagnostic
      capabilities, supportive care, and training.

PMID- 24039164
TI  - Recommendations to improve wildlife exposure estimation for development of soil
      screening and cleanup values.
AB  - An integral component in the development of media-specific values for the
      ecological risk assessment of chemicals is the derivation of safe levels of
      exposure for wildlife. Although the derivation and subsequent application of
      these values can be used for screening purposes, there is a need to identify the
      threshold for effects when making remedial decisions during site-specific
      assessments. Methods for evaluation of wildlife exposure are included in the US
      Environmental Protection Agency (USEPA) ecological soil screening levels (Eco
      SSLs), registration, evaluation, authorization, and restriction of chemicals
      (REACH), and other risk-based soil assessment approaches. The goal of these
      approaches is to ensure that soil-associated contaminants do not pose a risk to
      wildlife that directly ingest soil, or to species that may be exposed to
      contaminants that persist in the food chain. These approaches incorporate broad
      assumptions in the exposure and effects assessments and in the risk
      characterization process. Consequently, thresholds for concluding risk are
      frequently very low with conclusions of risk possible when soil metal
      concentrations fall in the range of natural background. A workshop held in
      September, 2012 evaluated existing methods and explored recent science about
      factors to consider when establishing appropriate remedial goals for
      concentrations of metals in soils. A Foodweb Exposure Workgroup was organized to
      evaluate methods for quantifying exposure of wildlife to soil-associated metals
      through soil and food consumption and to provide recommendations for the
      development of ecological soil cleanup values (Eco-SCVs) that are both practical
      and scientifically defensible. The specific goals of this article are to review
      the current practices for quantifying exposure of wildlife to soil-associated
      contaminants via bioaccumulation and trophic transfer, to identify potential
      opportunities for refining and improving these exposure estimates, and finally,
      to make recommendations for application of these improved models to the
      development of site-specific remedial goals protective of wildlife. Although the
      focus is on metals contamination, many of the methods and tools discussed are
      also applicable to organic contaminants. The conclusion of this workgroup was
      that existing exposure estimation models are generally appropriate when fully
      expanded and that methods are generally available to develop more robust site
      specific exposure estimates. Improved realism in site-specific wildlife Eco-SCVs
      could be achieved by obtaining more realistic estimates for diet composition,
      bioaccumulation, bioavailability and/or bioaccessibility, soil ingestion, spatial
      aspects of exposure, and target organ exposure. These components of wildlife
      exposure estimation should be developed on a site-, species-, and analyte
      specific basis to the extent that the expense for their derivation is justified
      by the value they add to Eco-SCV development.

PMID- 24039165
TI  - Dehydration of different ketoses and aldoses to 5-hydroxymethylfurfural.
AB  - 5-Hydroxymethylfurfural (HMF) is considered an important building block for
      future bio-based chemicals. Here, we present an experimental study using
      different ketoses (fructose, sorbose, tagatose) and aldoses (glucose, mannose,
      galactose) under aqueous acidic conditions (65 g L(-1) substrate, 100-160 
      degrees C, 33-300 mM H2 SO4 ) to gain insights into reaction pathways for hexose
      dehydration to HMF. Both reaction rates and HMF selectivities were significantly
      higher for ketoses than for aldoses, which is in line with literature. Screening
      and kinetic experiments showed that the reactivity of the different ketoses is a
      function of the hydroxyl group orientation at the C3 and C4 positions. These
      results, in combination with DFT calculations, point to a dehydration mechanism
      involving cyclic intermediates. For aldoses, no influence of the hydroxyl group
      orientation was observed, indicating a different rate-determining step. The
      combination of the knowledge from the literature and the findings in this work
      indicates that aldoses require an isomerization to ketose prior to dehydration to
      obtain high HMF yields.

PMID- 24039166
TI  - SPE of 5-lipoxygenase metabolites and the effect of head-column field-amplified
      sample stacking in MEKC.
AB  - The SPE of leukotrienes and eicosatetraenoic acids using anion exchange materials
      was compared to the classical extraction with C18 columns. A silica-based strong
      anion exchanger, a polymer-based weak anion exchanger, and a polymer-based mixed
      mode strong anion exchanger were studied. All anion exchange materials displayed
      a higher recovery of the analytes with values between 70 and 90% when extracting
      standard solutions and analyzing by HPLC. The effect was less pronounced for the
      analysis of the compounds in incubations of polymorphonuclear leukocytes. Using
      MEKC with head-column field-amplified sample stacking for analyte quantification,
      much lower values of the peak areas were observed compared to the determination
      of the recovery of the analytes by HPLC. Using MEKC analysis, the highest values
      were found for the polymer-based weak anion exchange material, while values below
      10% were found for the polymer-based mixed mode strong anion exchanger. This
      could be attributed to the presence of electrolytes in the eluates that
      compromised the stacking efficiency. The extent of residual electrolytes depended
      on the SPE protocol, resulting in large differences of the amount of analyte
      determined by MEKC when applying head-column field-amplified sample stacking for
      online analyte concentration. 

PMID- 24039167
TI  - Exhaled nitric oxide and wheezing phenotypes.

PMID- 24039168
TI  - Metal-based compounds as prospective antileishmanial agents: inhibition of
      trypanothione reductase by selected gold complexes.
AB  - Picking a fight with parasites! Trypanothione reductase (TR) is a validated drug
      target for the development of antileishmanial agents. A group of structurally
      diverse gold-containing compounds was evaluated in vitro for TR inhibition. A
      number of compounds exhibited potent activity and deserve further pharmacological
      evaluation. 

PMID- 24039169
TI  - Total serum immunoglobulin E as a marker for missed antigens on in vitro allergy
      screening.
AB  - BACKGROUND: The diagnosis of inhalant allergies involves a medical history,
      physical exam, and allergen sensitivity testing; allergen sensitivity can be
      assessed by a specific immunoglobulin E (IgE) screen for inhalant allergens. Some
      patients with clinical suspicion for inhalant allergies have a negative specific
      IgE screen, but high total IgE. We theorize that elevated total IgE may indicate
      a false-negative screen caused by "missed allergens" not initially identified.
      METHODS: Study patients with a negative allergy screen and elevated IgE (>116
      kU/L) were identified (n = 26). Control patients (n = 26) were defined as having
      a negative screen and an IgE <2.95 kU/L. Both groups were tested with an expanded
      specific IgE panel and completed a questionnaire about other causes of elevated
      IgE. RESULTS: The expanded panel was positive for inhalant allergens in 4 study
      patients (15%) and 0 control patients (p = 0.037). Within the study patients, 50%
      had asthma and 76.9% had chronic sinusitis. Only 2 control patients had asthma
      (11.5%), p = 0.003; 4 (19.2%) reported chronic sinusitis, p < 0.0001. Food
      allergen sensitivity was identified in 5 study patients and 1 control, p = 0.083.
      CONCLUSION: This pilot study evaluated patients clinically suspected of allergy
      with a negative inhalant IgE screen. Those with a high total IgE were more likely
      to have a missed inhalant allergen on expanded testing, as well as asthma and
      chronic sinusitis, compared to those with a low total IgE. Further investigation
      of "missed antigen" and the role of chronic respiratory inflammatory disease in
      patients with elevated total IgE is warranted.

PMID- 24039170
TI  - Suppression of cancer-initiating cells and selection of adipose-derived stem
      cells cultured on biomaterials having specific nanosegments.
AB  - Cancer-initiating cells [cancer stem cells (CSCs)] in colon cancer cells can be
      selectively suppressed when they are cultured on Pluronic (nanosegment)-grafted
      dishes, whereas CSCs are maintained on conventional tissue culture dishes and
      extracellular matrix-coated dishes. CSCs persist in tumors as a distinct
      population and cause relapse and metastasis by giving rise to new tumorigenic
      clones. The purification or depletion (suppression) of CSCs should be useful for
      analyzing CSC characteristics and for clinical application. CSCs can be
      selectively suppressed from colon cancer cells containing adipose-derived stem
      cells (ADSCs) on Pluronic-grafted dishes, while ADSCs remain on the dishes. ADSCs
      on Pluronic-grafted dishes after the suppression of the CSCs can differentiate
      into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, and neuronal cells.
      The CSCs and ADSCs exhibited different characteristics. The selection of ADSCs
      was possible on Pluronic-grafted dishes that suppressed the CSCs from the fat
      tissues of cancer patients (i.e., cell-sorting dishes), which was explained by
      specific biomedical characteristics of Pluronic.

PMID- 24039171
TI  - An interplay between transcription, processing, and degradation determines tRNA
      levels in yeast.
AB  - tRNA biogenesis in yeast involves the synthesis of the initial transcript by RNA
      polymerase III followed by processing and controlled degradation in both the
      nucleus and the cytoplasm. A vast landscape of regulatory elements controlling
      tRNA stability in yeast has emerged from recent studies. Diverse pathways of tRNA
      maturation generate multiple stable and unstable intermediates. A significant
      impact on tRNA stability is exerted by a variety of nucleotide modifications. Pre
      tRNAs are targets of exosome-dependent surveillance in the nucleus. Some tRNAs
      that are hypomodified or bear specific destabilizing mutations are directed to
      the rapid tRNA decay pathway leading to 5'->3' exonucleolytic degradation by Rat1
      and Xrn1. tRNA molecules are selectively marked for degradation by a double CCA
      at their 3' ends. In addition, under different stress conditions, tRNA half
      molecules can be generated by independent endonucleolytic cleavage events. Recent
      studies reveal unexpected relationships between the subsequent steps of tRNA
      biosynthesis and the mechanisms controlling its quality and turnover.

PMID- 24039172
TI  - Hydroxypropyl cellulose methacrylate as a photo-patternable and biodegradable
      hybrid paper substrate for cell culture and other bioapplications.
AB  - In addition to the choice of appropriate material properties of the tissue
      construct to be used, such as its biocompatibility, biodegradability,
      cytocompatibility, and mechanical rigidity, the ability to incorporate
      microarchitectural patterns in the construct to mimic that found in the cellular
      microenvironment is an important consideration in tissue engineering and
      regenerative medicine. Both these issues are addressed by demonstrating a method
      for preparing biodegradable and photo-patternable constructs, where modified
      cellulose is cross-linked to form an insoluble structure in an aqueous
      environment. Specifically, hydroxypropyl cellulose (HPC) is rendered
      photocrosslinkable by grafting with methylacrylic anhydride, whose linkages also
      render the cross-linked construct hydrolytically degradable. The HPC is then
      cross-linked via a photolithography-based fabrication process. The feasibility of
      functionalizing these HPC structures with biochemical cues is verified post
      fabrication, and shown to facilitate the adhesion of mesenchymal progenitor
      cells. The HPC constructs are shown to be biocompatible and hydrolytically
      degradable, thus enabling cell proliferation and cell migration, and therefore
      constituting an ideal candidate for long-term cell culture and implantable tissue
      scaffold applications. In addition, the potential of the HPC structure is
      demonstrated as an alternative substrate to paper microfluidic diagnostic devices
      for protein and cell assays. 

PMID- 24039174
TI  - Plasma metabolites of dietary flavonoids after combination meal consumption with
      onion and tofu in humans.
AB  - SCOPE: The effect of food combination on metabolic profile in postprandial plasma
      has hardly been reported. We investigated the absorption and metabolism of
      quercetin and soy isoflavones in humans after combination meal consumption.
      METHODS AND RESULTS: Five healthy volunteers ingested sauteed onion and tofu, and
      the plasma metabolites of quercetin and isoflavones were analyzed. Quercetin and
      genistein were incubated with human intestinal Caco-2 cells and human hepatoma
      HepG2 cells to further analyze the influence of simultaneous supply to the small
      intestine and the liver. Glucuronosyl conjugates of quercetin and methylated
      quercetin were the major plasma metabolites in the case of onion intake. Plasma
      metabolites with the single serving of tofu were both glucuronide and sulfate
      metabolites of isoflavones. Interestingly, quercetin sulfate was only detected
      after the combined intake of sauteed onion and tofu, accompanied with a decrease
      in sulfated isoflavones. Besides, quercetin was shown as the preferential
      substance for phase II enzymes over genistein in both Caco-2 and HepG2 cells.
      CONCLUSION: These results indicate that, when flavonoids and isoflavonoids were
      ingested together, the metabolic conversions in the small intestine and/or the
      liver could be altered, resulting in the variation of the postprandial profiles
      of the plasma metabolites.

PMID- 24039173
TI  - Genetic predictors of risk and resilience in psychiatric disorders: a cross
      disorder genome-wide association study of functional impairment in major
      depressive disorder, bipolar disorder, and schizophrenia.
AB  - Functional impairment is one of the most enduring, intractable consequences of
      psychiatric disorders and is both familial and heritable. Previous studies have
      suggested that variation in functional impairment can be independent of symptom
      severity. Here we report the first genome-wide association study (GWAS) of
      functional impairment in the context of major mental illness. Participants of
      European-American descent (N = 2,246) were included from three large treatment
      studies of bipolar disorder (STEP-BD) (N = 765), major depressive disorder
      (STAR*D) (N = 1091), and schizophrenia (CATIE) (N = 390). At study entry,
      participants completed the SF-12, a widely used measure of health-related quality
      of life. We performed a GWAS and pathway analysis of the mental and physical
      components of health-related quality of life across diagnosis (~1.6 million
      single nucleotide polymorphisms), adjusting for psychiatric symptom severity.
      Psychiatric symptom severity was a significant predictor of functional
      impairment, but it accounted for less than one-third of the variance across
      disorders. After controlling for diagnostic category and symptom severity, the
      strongest evidence of genetic association was between variants in ADAMTS16 and
      physical functioning (P = 5.87 * 10(-8) ). Pathway analysis did not indicate
      significant enrichment after correction for gene clustering and multiple testing.
      This study illustrates a phenotypic framework for examining genetic contributions
      to functional impairment across psychiatric disorders.

PMID- 24039175
TI  - Carbon nitride for the selective oxidation of aromatic alcohols in water under
      visible light.
AB  - The selective oxidation of aromatic alcohols in water is achieved by using a
      carbon nitride (CN) catalyst, dioxygen, and visible light. The unique electronic
      structure of CN avoids the direct formation of hydroxyl radicals, which typically
      cause the total oxidation of organics. The chemical stability of CN allows
      several chemical protocols for photoredox catalysis in water, as exemplified by
      cooperative catalysis involving Bronsted acids. This leads to a new, green
      pathway for diverse organic transformations using sunlight and water. 

PMID- 24039176
TI  - A comparison of septal stapler to suture closure in septoplasty: a prospective,
      randomized trial evaluating the effect on operative time.
AB  - BACKGROUND: Septoplasty requires coaptation of the mucosal flaps at the
      conclusion of the procedure; classically this is done with nasal packing.
      Quilting sutures provide a welcome alternative to packing, but can be time
      consuming to place. A septal stapler has recently been developed that provides a
      rapid alternative to quilting sutures but the timesaving has not been quantified.
      METHODS: This study was a prospective, randomized trial comparing a septal
      stapler to quilting suture for coaptation of mucosal flaps in septoplasty. After
      meeting inclusion criteria, patients underwent septoplasty and inferior
      turbinoplasty. The total operative time, surgical segment times, including time
      for closure was recorded. Preoperative and postoperative Nasal Obstruction
      Symptom Evaluation (NOSE) scores were recorded. A sample size of 16 was
      determined to detect a difference of 5 minutes in closure time. RESULTS: A total
      of 16 patients were enrolled in the study. The mean time for closure with septal
      stapler was 35 +/- 22 seconds vs 7 minutes +/- 1 minute 10 seconds for suture
      closure (p < 0.0001). The mean total operative time using the septal stapler was
      28 minutes +/- 6 minutes whereas 43 minutes +/- 13 minutes was required for
      suture (p = 0.014). No difference in postoperative complications or mucosal
      healing was seen; preoperative and postoperative improvement in NOSE scores was
      comparable. CONCLUSION: Coaptation of the mucosal flaps in septoplasty with a
      septal stapler affords a timesaving in the operating room with no difference in
      operative outcome.

PMID- 24039177
TI  - The diagnosis of malignant mesothelioma in effusion cytology: a reappraisal and
      results of a multi-institution survey.
AB  - BACKGROUND: The diagnosis of malignant mesothelioma (MM) in effusion specimens is
      controversial. At the study institution (Northwestern University), a primary
      diagnosis of MM is made on fluid cytology specimens. In an effort to estimate the
      practice at other institutions, a survey was disseminated regarding cytologic
      diagnosis of MM. The authors also evaluated their own institution's experience
      with primary cytologic diagnosis of MM. METHODS: Patients with MM at the study
      institution were identified from 1992 through 2011. Fluid cytology specimens
      preceding histologic diagnoses were reviewed. A survey was sent to a number of
      cytology laboratories to assess practice patterns regarding the diagnosis of MM.
      RESULTS: At the study institution, 20 cases of MM had effusion specimens
      preceding the diagnostic histologic material. In 6 cases (30%), a definitive
      diagnosis of MM was rendered via cytology alone. There were no false-positive
      diagnoses of MM. Of 55 laboratories that responded to the survey, 36 reported
      making a definitive diagnosis of MM after cytologic analysis. Almost all
      laboratories (35) willing to diagnose MM in effusions reported performing
      immunohistochemistry to distinguish adenocarcinoma from MM. A smaller proportion
      (18) of these laboratories reported doing additional immunohistochemistry or
      fluorescence in situ hybridization for p16 to help distinguish benign from
      malignant mesothelial proliferations. Those who do not definitively diagnose MM
      in fluid specimens state inability to identify invasion and overlap with reactive
      mesothelial proliferation as factors supporting their practice. Most respondents
      (32) felt that the clinicians at their institution would manage a patient based
      on a cytologic diagnosis of MM. CONCLUSIONS: The majority of respondents reported
      making a definitive diagnosis of MM in effusion cytology specimens. The diagnosis
      of MM in effusions, although not sensitive, is extremely specific.

PMID- 24039178
TI  - Ionic-liquid-based dispersive liquid-liquid microextraction for high-throughput
      multiple food contaminant screening.
AB  - This paper describes an innovation of dispersive liquid-liquid microextraction
      enabling multiple-component analysis of eight high-priority food contaminants in
      two chemically distinctive families: Sudan dyes and phthalate plasticizers. To
      provide convenient sample handling for solid and solid-containing matrices, a
      modified dispersive liquid-liquid microextraction procedure used an extractant
      precoated frit to perform simultaneous filtration, solvent mixing, and phase
      dispersion in one simple step. A binary ionic liquid extractant system was
      carefully tuned to deliver high quality analysis based only on affordable LC with
      diode array detector instrumentation. The method is comprehensively validated for
      robust quantification with good precision (6.9-9.8% RSD) in a linear 2-1000 MUg/L
      range. Having accomplished enrichment factors up to 451, the treatment enables
      sensitive detection at 0.09-1.01 MUg/L levels. Analysis of six high-risk solid
      condiments and sauces further verified its practical applicability within a 70
      120% recovery range. Compared to other approaches, the current dispersive liquid
      liquid microextraction treatment offers major advantages in terms of minimal
      solvent (1.5 mL) and sample (0.1 g) consumption, ultra-high analytical throughput
      (6 min), and the ability to handle complex solid matrices. The idea of performing
      simultaneous analysis for multiple contaminants presented here fosters a more
      effective mode of operation in food control routines. 

PMID- 24039179
TI  - Anti-HIV-1 peptide derivatives based on the HIV-1 Co-receptor CXCR4.
AB  - The human immunodeficiency virus type 1 (HIV-1) uses CD4 and the co-receptor CCR5
      or CXCR4 in the process of cell entry. The negatively charged extracellular
      domains of CXCR4 (CXCR4-ED) interact with positive charges on the V3 loop of
      gp120, facilitating binding via electrostatic interactions. The presence of
      highly conserved positively charged residues in the V3 loop suggests that CXCR4
      ED-derived inhibitors might be broadly effective inhibitors. Synthetic peptide
      derivatives were evaluated for anti-HIV-1 activity. The 39-mer extracellular N
      terminal region (NT) was divided into three fragments with 10-mer overlapping
      sites (N1-N3), and these linear peptides were synthesized. Peptide N1 contains
      Met 1-Asp 20 and shows significant anti-HIV-1 activity. Extracellular loops 1 and
      2 (ECL1 and 2) were mimicked by cyclic peptides C1 and C2, which were synthesized
      by chemoselective cyclization. Cyclic peptides C1 and C2 show higher anti-HIV-1
      activity than their linear peptide counterparts, L1 and L2. The cytotoxicities of
      C1 and C2 are lower than those of L1 and L2. These results indicate that Met 1
      Asp 20 segments of the NT and cyclic peptides of ECL1 and ECL2 are potent anti
      HIV-1 drug candidates. 

PMID- 24039180
TI  - RNAs with multiple personalities.
AB  - In the last decade, advances in sequencing technology and a renewed focus on the
      regulatory potential of RNA molecules have combined to stimulate an enormous
      expansion in the catalog of known eukaryotic RNAs. Beyond the sheer numerical
      diversity of RNA species, recent studies have begun to uncover hints of even
      greater functional complexity. An increasing number of RNA molecules, including
      those from classic, well-studied classes, have been found to act in previously
      unanticipated regulatory roles, or as substrate for the biogenesis of
      functionally distinct RNA molecules, or both. Thus, these molecules can fulfill
      multiple, parallel functions, compounding the already rich landscape of RNA
      biology, and potentially connecting disparate biological regulatory networks in
      unexpected ways. In this article, we review recently discovered instances of RNA
      multifunctionality, with a particular focus on regulatory small RNAs.

PMID- 24039181
TI  - Graphene-mesoporous silica-dispersed palladium nanoparticles-based probe carrier
      platform for electrocatalytic sensing of telomerase activity at less than single
      cell level.
AB  - Human telomerase is a specialized ribonucleoprotein polymerase and is used as a
      clinical cancer marker and special target for chemotherapy. Traditional
      telomerase detection uses "telomerase repeat amplification protocol" (TRAP)
      assay. However, TRAP is questioned because it requires use of DNA polymerases,
      which is susceptible to polymerase chain reaction (PCR)-derived artifacts and
      time-consuming. Here, a novel PCR-free, electrocatalytic assay for signal
      amplified detection of telomerase activity using graphene-mesoporous silica
      dispersed palladium nanoparticles-based probe carrier platform to improve probe
      target recognition is reported. The low background noise is achieved by using DNA
      site-specific cleavage endonuclease and the detection signal is amplified by
      using hemoglobin. As a highly efficient electron sink, hemoglobin does not carry
      out direct reduction at the surface, minimizing false positives. These merits
      make this assay highly sensitive, achieving the sensitivity comparable to TRAP.
      The developed electrocatalysis assay is PCR-free, simple in design, and fast in
      operation, therefore avoiding PCR amplification-related errors, which make it
      more reliable to evaluate telomerase activity for clinical use. 

PMID- 24039182
TI  - Epigallocatechin-3-gallate, a DYRK1A inhibitor, rescues cognitive deficits in
      Down syndrome mouse models and in humans.
AB  - SCOPE: Trisomy for human chromosome 21 results in Down syndrome (DS), which is
      among the most complex genetic perturbations leading to intellectual disability.
      Accumulating data suggest that overexpression of the dual-specificity tyrosine
      (Y)-phosphorylation regulated kinase 1A (DYRK1A), is a critical pathogenic
      mechanisms in the intellectual deficit. METHODS AND RESULTS: Here we show that
      the green tea flavonol epigallocatechin-gallate (EGCG), a DYRK1A inhibitor,
      rescues the cognitive deficits of both segmental trisomy 16 (Ts65Dn) and
      transgenic mice overexpressing Dyrk1A in a trisomic or disomic genetic
      background, respectively. It also significantly reverses cognitive deficits in a
      pilot study in DS individuals with effects on memory recognition, working memory
      and quality of life. We used the mouse models to ensure that EGCG was able to
      reduce DYRK1A kinase activity in the hippocampus and found that it also induced
      significant changes in plasma homocysteine levels, which were correlated with
      Dyrk1A expression levels. Thus, we could use plasma homocysteine levels as an
      efficacy biomarker in our human study. CONCLUSION: We conclude that EGCG is a
      promising therapeutic tool for cognitive enhancement in DS, and its efficacy may
      depend of Dyrk1A inhibition.

PMID- 24039183
TI  - Analysis of risk factors of cord blood transplantation for children.
AB  - BACKGROUND: As cord blood (CB) is being used frequently as a source for
      heamtopoetic stem cell transplantation defining risk factors for transplantation
      outcome is an important issue. PROCEDURE: The data of all single unit CB
      transplantation preformed in Israel from 1992 to 2011 were collected. The risk
      factors for myeloid engraftment, event free survival (EFS) and overall survival
      (OS) were studied in 87 children. RESULTS: There were 49 children with
      hematological malignancies and 38 with non-malignant diseases. Cumulative rate of
      neutrophil recovery was 78.3%, while median time to myeloid recovery was 26 days.
      The incidence of platelet engraftment at 150 days was 53%, and the median time to
      platelet recovery was 36 days. ABO blood group matching between CB unit and
      recipient was associated with superior myeloid engraftment. Acute graft versus
      host disease of grades II-IV occurred in 33% of the patients. Chronic graft
      versus host disease occurred in 16% of patients. Probabilities of EFS and OS at 1
      year were 45% and 57%, respectively. Factors associated with inferior OS were Rh
      major mismatch versus matched Rh and transplantation from unrelated donor versus
      related donor. CONCLUSIONS: These results indicate that matching of ABO blood
      groups is an important factor that affects engraftment, and also that Rh matching
      seem to have an impact on OS, which was not previously described in the setting
      of CB transplantation.

PMID- 24039184
TI  - Utilization of flax fibers for biomedical applications.
AB  - Over the past decades, a large number of animal-derived materials have been
      introduced for several biomedical applications. Surprisingly, the use of plant
      based materials has lagged behind. To study the feasibility of plant-derived
      biomedical materials, we chose flax (Linum usitatissimum). Flax fibers possess
      excellent physical-mechanical properties, are nonbiodegradable, and there is
      extensive know-how on weaving/knitting of them. One area where they could be
      useful is as implantable mesh structures in surgery, in particular for the repair
      of incisional hernias of the abdominal wall. Starting with a bleached flax
      thread, a prototype mesh was specifically knitted for this study, and its
      cytocompatibility was studied in vitro and in vivo. The experimental data
      revealed that application of flax in surgery first requires a robust method to
      remove endotoxins and purify the flax fiber. Such a method was developed, and
      purified meshes did not cause loss of cell viability in vitro. In addition,
      endotoxins determined using limulus amebocyte lysate test were at acceptable
      levels. In vivo, the flax meshes showed only mild inflammation, comparable to
      commercial polypropylene meshes. This study revealed that plant-derived
      biomaterials can provide a new class of implantable materials that could be used
      as surgical meshes or for other biomedical applications.

PMID- 24039185
TI  - What is the most adapted indication of prophylactic pancreatic duct stent within
      the high-risk group of post-endoscopic retrograde cholangiopancreatography
      pancreatitis? Using the propensity score analysis.
AB  - BACKGROUND: Conducting randomized controlled trial (RCT) for each of the risk
      factors associated with prophylactic pancreatic duct stent (PPDS) for post
      endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is
      difficult owing to the volume of cases and ethical considerations. In this study,
      we tried to reveal the degree of preventive effects of PPDS for each individual
      risk factor within the high-risk group of PEP using the propensity score
      analysis. METHODS: The clinical data of 1131 ERCP practices performed at Kobe
      University Hospital from April 2006 to February 2009 were collected
      prospectively. We investigated their clinical characteristics including the risk
      factors of PEP, the use of PPDS and complications of ERCP. We conducted the
      stratification analysis using the propensity score matching analysis. RESULTS: In
      210 propensity score-matched ERCPs, PPDS proved to be effective in preventing PEP
      in patients with a history of pancreatitis (odds ratio 0.11, 95% CI 0.01-0.76, P
      = 0.01) and cases of difficult cannulation (requiring more than 30 min) (odds
      ratio 0.13, 95% CI 0.01-1.14, P = 0.08). CONCLUSIONS: Patients with a history of
      pancreatitis and cases of difficult cannulation are strongly recommended for PPDS
      placement. The propensity score analysis can be adapted to the ERCP-related
      analysis with many procedure-related factors with using retrospective data, and
      may be adapted to investigate the matters that are unsuitable for RCT by volume
      and ethical issue.

PMID- 24039186
TI  - The use of convex probe endobronchial ultrasound-guided transbronchial needle
      aspiration in a pediatric population: a multicenter study.
AB  - INTRODUCTION: The presence of intrathoracic lymphadenopathy and mediastinal
      masses in the pediatric population often presents a diagnostic challenge. With
      limited minimally invasive methodologies to obtain a diagnosis, invasive sampling
      via mediastinoscopy or thoracotomy is often pursued. Endobronchial ultrasound
      transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive, outpatient
      procedure that has demonstrated significant success in the adult population in
      the evaluation of such abnormalities. Within the pediatric literature there is
      limited data regarding the use of EBUS-TBNA. We report the first multicenter
      review of a pediatric population undergoing EBUS-TBNA procedures identifying the
      feasibility, safety, utility, and outcomes of this procedure. METHODS: All
      patients of 18 years of age or younger undergoing EBUS-TBNA at six major academic
      medical centers from the years 2007 through 2013 were reviewed. Data regarding
      procedural performance, outcomes, and complications were recorded. RESULTS: A
      total of 21 patients meeting the inclusion criteria were identified in six
      centers. The mean age of the cohort was 13.7 (+/-4.1) years. EBUS-TBNA provided
      adequate sampling in 20/21 (95%) of the cases with diagnostic material obtained
      in 10 (48%) cases. Eight patients (38%) underwent additional surgical procedures
      to confirm or obtain diagnostic tissue. Within our cohort, 13 patients (62%) were
      able to avoid invasive surgical biopsy procedures. No procedural or anesthesia
      related complications were identified. CONCLUSION: We report the first
      multicenter study to date confirming the feasibility and utility of EBUS-TBNA in
      the pediatric population. Due to the low overall procedural risk of EBUS-TBNA, it
      should be considered as a potential first line diagnostic option for children
      presenting with mediastinal or hilar abnormalities but further prospective
      studies are needed.

PMID- 24039187
TI  - The AKT genes and their roles in various disorders.
AB  - AKT (AK mouse plus Transforming or Thymoma) is a common oncogene expressed in
      most tissues. Both AKT2 and AKT3, although important, have more limited
      distributions. The regulation of all three genes depends on two receptors-a
      receptor tyrosine kinase with a growth factor ligand, and a G protein coupled
      receptor, also with a ligand together with an explanation of how their downsteam
      components function. AKT2 is amplified or overexpressed in cancer with a higher
      frequency than those found with AKT1. AKT1 is cardioprotective to the heart by
      supporting its physiological growth and function. AKT2 is closely linked to Type
      II diabetes and the implications of various types of mutations are discussed.
      Various AKT3 mutations are important in neurological disorders, such as
      microcephaly, hemimegalencephaly, and megalencephaly syndromes. Finally, a
      reduced level of AKT1 in the frontal cortex has been found during post-mortem
      brain studies of schizophrenic patients in the populations of many countries.

PMID- 24039188
TI  - Image-guidance in endoscopic sinus surgery: is it associated with decreased
      medicolegal liability?
AB  - BACKGROUND: The use of image-guidance (IG) in endoscopic sinus surgery (ESS) has
      escalated over the last decade despite a lack of consensus that its use improves
      outcomes or decreases complications. One theoretical reason for using IG in ESS
      is its potential to minimize legal liability should an adverse outcome occur. In
      this study, we aimed to characterize the role of IG in ESS litigation, and
      further detail other factors in pertinent cases. A secondary objective was to
      characterize recent malpractice litigation for other relevant factors. METHODS:
      Relevant cases from Westlaw were examined to determine whether the use of IG
      played a role in initiating litigation in ESS malpractice suits. Factors such as
      patient demographics and alleged cause(s) of malpractice litigation were
      examined. RESULTS: Out of 30 malpractice cases from 2004 to April 2013, 4 (13.3%)
      mentioned the use of IG during ESS, although this did not appear to be a factor
      affecting the plaintiff's decision to initiate litigation, nor the case outcomes.
      In the 26 cases (86.7%) in which IG was not used, its non-use was not specified
      as an alleged cause of negligence. Eleven (36.7%) cases were resolved in the
      defendant's favor. Frequently-cited factors included iatrogenic injury (83.3%),
      permanent deficits (66.7%), needing additional surgery (63.3%), orbital and
      intracranial injury, and perceived deficits in informed consent (40.0%).
      CONCLUSION: The use of IG was not found to be a factor in ESS litigation. This
      suggests that not using IG does not necessarily make one more vulnerable to
      malpractice litigation.

PMID- 24039189
TI  - Changing the cytology laboratory information system to improve cytology
      performance.
AB  - A central tenet in the Patient Protection and Affordable Care Act is the
      increased use of information technology to improve patient care. However, areas
      for improvement in cytology are not well defined. Improvements in information
      technology could improve quality assessment in gynecologic cytology, but the
      cytology community must identify and ask for changes in information technology
      that can improve the care of patients. Cancer (Cancer Cytopathol) 2014;122:87-91.
      (c) 2013 American Cancer Society. 

PMID- 24039190
TI  - Quinoline carboxamide-type ABCG2 modulators: indole and quinoline moieties as
      anilide replacements.
AB  - ABC, it's easy as 1 2 3! Bioisosteric replacement of the anilide core by an
      indole moiety considerably increased stability and gave potent and selective
      ABCG2 (BCRP) inhibitors. Some compounds are superior to the reference substances
      fumitremorgin C and Ko143 in terms of potency and efficacy and are the most
      potent ABCG2 modulators reported so far. 

PMID- 24039191
TI  - Determination of 48 fragrance allergens in toys using GC with ion trap MS/MS.
AB  - This paper presents a method for the simultaneous determination of 48 fragrance
      allergens in four types of toys (plastic toys, play clays, plush toys, and paper
      toys) based on GC with ion trap MS/MS. Compared with single-stage MS, MS/MS is
      superior in terms of the qualification and quantification of a large range of
      compounds in complicated matrices. Procedures for extraction and purification
      were optimized for each toy type. The method proved to be linear over a wide
      range of concentrations for all analytes with correlation coefficients between
      0.9768 and 0.9999. Validation parameters, namely, LODs and LOQs, ranged from
      0.005-5.0 and from 0.02-20 mg/kg, respectively. Average recoveries of target
      compounds (spiked at three concentration levels) were in the range of 79.5
      109.1%. Intraday and interday repeatabilities of the proposed method varied from
      0.7-10.5% and from 3.1-13.4%, respectively. The proposed method was used to
      monitor fragrance allergens in commercial toy products. Our findings indicate
      that this method is an accurate and effective technique for analyzing fragrance
      allergens in materials composed of complex components. 

PMID- 24039192
TI  - Autophagy-sensitized cytotoxicity of quantum dots in PC12 cells.
AB  - Both CdTe and CdTe/CdS/ZnS quantum dots induce similar levels of autophagy in
      PC12 and HEK293 cells, while the former exhibits higher toxicity. Low levels of
      cadmium ions are not sufficient to induce either autophagy or cytotoxicity by
      themselves. Interestingly, the combination of cadmium ions and CdTe/CdS/ZnS
      mimics the toxic effect of CdTe, suggesting that autophagy sensitizes cells to
      cadmium ions. 

PMID- 24039194
TI  - Extended duration of prehydration does not prevent nephrotoxicity or delayed drug
      elimination in high-dose methotrexate infusions: a prospectively randomized cross
      over study.
AB  - BACKGROUND: Alkalized hydration is used as supportive care to prevent renal
      toxicity during infusions with high-dose methotrexate (HDMTX). In children with
      acute lymphoblastic leukemia (ALL), the hydration is commonly initiated 4 hours
      before start of the methotrexate (MTX) infusion. To test if longer duration of
      prehydration would prevent MTX-induced renal toxicity, we preformed a randomized
      cross-over study comparing 12-4 hours of hydration before the infusion of HDMTX.
      PROCEDURES: Children with ALL and non-Hodgkin lymphoma that were treated with
      infusions of HDMTX 5 or 8 g/m(2) were randomized to receive intravenous
      prehydration 12 or 4 hours before the first HDMTX infusion. Patients alternated
      between 12 and 4 hours of prehydration in the subsequent HDMTX infusions. Renal
      toxicity was defined as 50% increase in plasma creatinine after the HDMTX
      infusion. The plasma MTX concentration was measured during and after the HDMTX
      infusion to determine if the duration of prehydration would influence the
      systemic MTX clearance. RESULTS: A total of 47 patients (224 HDMTX infusions)
      with a median age of 4.9 years were included in the study. The duration of
      prehydration had no effect on MTX induced renal toxicity that occurred in 18.5%
      of all HDMTX 5 g/m(2) infusions and in 40.0% of all HDMTX 8 g/m(2) infusions.
      Similar the duration of prehydration had no impact on the systemic clearance of
      MTX. CONCLUSION: Extending prehydration beyond 4 hours does not reduce the risk
      of renal toxicity or delayed MTX clearance after infusions with HDMTX 5-8 g/m(2).

PMID- 24039193
TI  - Synergistic induction of human cathelicidin antimicrobial peptide gene expression
      by vitamin D and stilbenoids.
AB  - SCOPE: The cathelicidin antimicrobial peptide (CAMP) gene is induced by 1alpha,25
      dihydroxyvitamin D3 (1alpha,25(OH)2 D3), lithocholic acid, curcumin,
      nicotinamide, and butyrate. Discovering additional small molecules that regulate
      its expression will identify new molecular mechanisms involved in CAMP regulation
      and increase understanding of how diet and nutrition can improve immune function.
      METHODS AND RESULTS: We discovered that two stilbenoids, resveratrol and
      pterostilbene, induced CAMP promoter-luciferase expression. Synergistic
      activation was observed when either stilbenoid was combined with 1alpha,25(OH)2
      D3. Both stilbenoids increased CAMP mRNA and protein levels in the monocyte cell
      line U937 and synergy was observed in both U937 and the keratinocyte cell line,
      HaCaT. Inhibition of resveratrol targets sirtuin-1, cyclic AMP production and the
      c-Jun N-terminal, phosphoinositide 3 and AMP-activated kinases did not block
      induction of CAMP by resveratrol or synergy with 1alpha,25(OH)2 D3. Nevertheless,
      inhibition of the extracellular signal regulated 1/2 and p38 mitogen-activated
      protein kinases, increased CAMP gene expression in combination with
      1alpha,25(OH)2 D3 suggesting that inhibition of these kinases by resveratrol may
      explain, in part, its synergy with vitamin D. CONCLUSION: Our findings
      demonstrate for the first time that stilbenoid compounds may have the potential
      to boost the innate immune response by increasing CAMP gene expression,
      particularly in combination with 1alpha,25(OH)2 D3.

PMID- 24039195
TI  - Porcine circovirus (PCV) removal by Q sepharose fast flow chromatography.
AB  - The recently discovered contamination of oral rotavirus vaccines led to exposure
      of millions of infants to porcine circovirus (PCV). PCV was not detected by
      conventional virus screening tests. Regulatory agencies expect exclusion of
      adventitious viruses from biological products. Therefore, methods for
      inactivation/removal of viruses have to be implemented as an additional safety
      barrier whenever feasible. However, inactivation or removal of PCV is difficult.
      PCV is highly resistant to widely used physicochemical inactivation procedures.
      Circoviruses such as PCV are the smallest viruses known and are not expected to
      be effectively removed by currently-used virus filters due to the small size of
      the circovirus particles. Anion exchange chromatography such as Q Sepharose((r))
      Fast Flow (QSFF) has been shown to effectively remove a range of viruses
      including parvoviruses. In this study, we investigated PCV1 removal by virus
      filtration and by QSFF chromatography. As expected, PCV1 could not be effectively
      removed by virus filtration. However, PCV1 could be effectively removed by QSFF
      as used during the purification of monoclonal antibodies (mAbs) and a log10
      reduction value (LRV) of 4.12 was obtained.

PMID- 24039196
TI  - Clinical and radiologic findings in a case series of maxillary sinusitis of
      dental origin.
AB  - BACKGROUND: Maxillary sinusitis of dental origin (MSDO) has been described for
      decades, but tends to be overlooked as a possible cause of chronic sinusitis by
      both clinicians and radiologists. The incidence of MSDO in published series is
      reported to be from 10% to 40% in bacterial sinusitis. We present this series to
      highlight clinical and radiologic indicators of MSDO. METHODS: Databases from the
      authors' otolaryngology and endodontic practices were reviewed to identify
      patients who had been seen mutually. Sixty-seven (67) patients were identified.
      Both authors then reviewed the clinical records and associated computed
      tomography (CT) scans and determined that 31 patients had MSDO and 2 of had
      bilateral MSDO, for a total of 33 cases. The clinical and radiologic features
      related to these cases were then tabulated. RESULTS: The clinical characteristics
      of the 33 cases of MSDO were as follows: sinus pain (88%), postnasal drainage
      (64%), congestion (45%), maxillary toothache (39%), and foul drainage (15%).
      Radiographic CT findings of MSDO showed periapical abscess in 18 cases (55%),
      periodontal abscess in 3 cases (9%), and no obvious dental pathology in 12 cases
      (36%). The extent of associated sinusitis was variable from mucoperiosteal
      thickening to florid unilateral sinusitis involving multiple sinuses. Eighteen
      maxillary sinuses (55%) were found to have either patent maxillary infundibula or
      prior surgical antrostomy. Twenty-four patients (77%) had unilateral maxillary
      sinus disease. CONCLUSION: MSDO should be considered highly likely when
      radiographic evidence of dental pathology is associated with maxillary sinus
      disease. Regardless of negative CT evidence of dental pathology, MSDO should be
      suspected when unilateral maxillary sinus disease is seen, particularly when
      associated with a patent infundibulum. When MSDO is suspected, a clinical
      endodontic examination should be performed to rule out or treat an odontogenic
      etiology.

PMID- 24039197
TI  - Organophosphorus catalysis to bypass phosphine oxide waste.
AB  - The conversion of oxygen-containing compounds is often achieved by the use of
      phosphorus reagents. The newly formed phosphine oxide bond delivers the enthalpic
      gain that drives reactions, such as the Wittig, Mitsunobu, and Appel reaction, to
      completion. However, phosphine oxides are recognized as undesirable waste
      products and in the past decade several methods have emerged that address this
      issue by in situ regeneration of the phosphorus reagent. This Minireview outlines
      the two distinct strategies and underpinning research that led to these advances.
      The potential of the emerging field of phosphorus catalysis in chemistry is shown
      and new developments that may stimulate further research are described.

PMID- 24039199
TI  - Model organisms proteomics--from holobionts to human nutrition.
AB  - Model organisms are an important tool for the development and validation of
      analytical approaches for proteomics and for the study of basic mechanisms of
      biological processes. The Initiative on Model Organism Proteomics (iMOP)
      organized a session during the 11th HUPO World Congress in Boston in 2012,
      highlighting the potential of proteomics studies in model organism for the
      elucidation of important mechanisms regulating the interaction of humans with its
      environment. Major subjects were the use of model organisms for the study of
      molecular events triggering the interaction of host organisms with the
      surrounding microbiota and the elucidation of the complex influence of nutrition
      on the health of human beings.

PMID- 24039205
TI  - Understanding the unconventional effects of halogenation on the luminescent
      properties of oligo(phenylene vinylene) molecules.
AB  - It is commonly known that halogenation tends to decrease the luminescence quantum
      yield of an organic dye, owing to the high electronegativity and heavy-atom
      effect of the halogen atom. However, based on an investigation of the effects of
      halogenation on the luminescence of the oligo(phenylene vinylene) (OPV)
      framework, we demonstrate that halogenation can have positive impact on the solid
      state fluorescence and electrochemiluminescence (ECL) properties of OPV
      derivatives. The chlorinated OPV exhibits a very high solid-state fluorescence
      quantum yield (91%), whilst the brominated analogue gives the highest ECL
      emission intensity. Time-dependent density functional theory calculations,
      natural bond orbital analysis, and natural transition orbital analysis were
      performed to assist the understanding of the origin of these positive
      halogenation effects, which provide insight into the rational design of highly
      luminescent halogenated organic materials for solid-state devices and ECL
      applications.

PMID- 24039204
TI  - Home-schooled children are thinner, leaner, and report better diets relative to
      traditionally schooled children.
AB  - OBJECTIVE: To examine and compare the relationships among diet, physical
      activity, and adiposity between home-schooled children (HSC) and traditionally
      schooled children (TSC). DESIGN AND METHODS: Subjects were HSC (n = 47) and TSC
      (n = 48) aged 7-12 years old. Dietary intakes were determined via two 24-h
      recalls and physical activity was assessed with 7 days of accelerometry. Fat mass
      (FM), trunk fat, and percent body fat (%BF) were measured by dual-energy X-ray
      absorptiometry (DXA). RESULTS: Relative to HSC, TSC demonstrated significantly
      higher BMI percentiles, FM, trunk fat, and %BF; consumed 120 total kilocalories
      more per day; and reported increased intakes of trans fats, total sugar, added
      sugars, calcium, and lower intakes of fiber, fruits, and vegetables (P < 0.05).
      At lunch, TSC consumed significantly more calories, sugar, sodium, potassium, and
      calcium compared to HSC (P < 0.05). Physical activity did not differ between
      groups. Traditional schooling was associated with increased consumption of trans
      fat, sugar, calcium (P < 0.05); lower intakes of fiber, and fruits and vegetables
      (P < 0.05); and higher FM, %BF, and trunk fat (P < 0.01), after adjustment for
      covariates. CONCLUSIONS: These data suggest HSC may consume diets that differ in
      energy and nutrient density relative to TSC, potentially contributing to
      differences in weight and adiposity.

PMID- 24039207
TI  - Effect of Bcl-x(L) overexpression on lactate metabolism in chinese hamster ovary
      cells producing antibody.
AB  - Previously, overexpression of anti-apoptotic proteins, such as E1B-19K and Aven,
      was reported to alter lactate metabolism of CHO cells in culture. To investigate
      the effect of Bcl-xL , a well-known anti-apoptotic protein, on lactate metabolism
      of recombinant CHO (rCHO) cells, two antibody-producing rCHO cell lines with
      regulated Bcl-xL overexpression (CS13*-0.02-off-Bcl-xL and CS13*-1.00-off-Bcl-xL
      ) were established using the Tet-off system. When cells were cultivated without
      Bcl-xL overexpression, the specific lactate production rate (qLac ) of CS13*-0.02
      off-Bcl-xL and CS13*-1.00-off-Bcl-xL were 7.32 +/- 0.37 and 6.78 +/- 0.56
      pmol/cell/day, respectively. Bcl-xL overexpression, in the absence of
      doxycycline, did not affect the qLac of either cell line, though it enhanced the
      viability during cultures. Furthermore, activities of the enzymes related to
      glucose and lactate metabolism, such as hexokinase, glucose-6-phosphate
      dehydrogenase, lactate dehydrogenases, and alanine aminotransferase, were not
      affected by Bcl-xL overexpression either. Taken together, Bcl-xL overexpression
      showed no significant effect on the lactate metabolism of rCHO cells.

PMID- 24039206
TI  - Value of immunohistochemistry in the detection of BRAF(V600E) mutations in fine
      needle aspiration biopsies of papillary thyroid carcinoma.
AB  - BACKGROUND: Fine-needle aspiration biopsy (FNAB) is important in the diagnostic
      establishment of suspicious thyroid nodules. In thyroid neoplasms, mutation of
      the BRAF gene occurs rather exclusively in papillary thyroid carcinoma (PTC) and
      results in>98% of the cases in V600E amino acid substitution. In the current
      study, the authors investigated the diagnostic value of a recently described
      monoclonal antibody that detects this specific mutation on FNAB specimens from
      patients with PTC. METHODS: BRAF(V600E) status of FNAB cell blocks from 55
      patients with PTC was analyzed by immunohistochemistry (IHC) with the new
      BRAF(V600E) antibody (clone VE1) and by Sanger sequencing (SaS). In discrepant
      cases, ultra-deep sequencing was also performed. Available corresponding
      histological specimens were investigated by IHC and, in selected cases, with SaS
      as well. RESULTS: All cases yielded evaluable IHC staining results of the cell
      block sections with good interobserver agreement (kappa value, 0.650). Ten tumors
      (18.2%) demonstrated no staining, 10 tumors (18.2%) demonstrated equivocal
      staining, 25 tumors (45.4%) demonstrated moderate staining, and 10 tumors (18.2%)
      demonstrated strong staining. SaS was able to be performed in 48 cases. Nineteen
      cases demonstrated wild-type BRAF and 29 cases were found to have the BRAF(V600E)
      mutation. After performing ultra-deep sequencing 1 false-positive and 2 false
      negative VE1 IHC cases remained, resulting in a sensitivity of 93.8% and a
      specificity of 93.8%. CONCLUSIONS: BRAF(V600E) mutations in FNAB specimens from
      patients with PTC can be reliably detected in most cases by IHC with a new
      mutation-specific antibody. Interpretation of VE1 IHC staining results on cell
      block slides of PTC can be difficult in some cases.

PMID- 24039208
TI  - Staphylococcus aureus biofilm activates the nucleotide-binding oligomerization
      domain containing 2 (Nod2) pathway and proinflammatory factors on a human
      sinonasal explant model.
AB  - BACKGROUND: The presence of Staphylococcus aureus biofilms on sinonasal mucosal
      surfaces is associated with recalcitrant chronic rhinosinusitis (CRS), but little
      is known about the innate immune response they trigger. We aimed to study the
      human pattern recognition receptor (PRR) nucleotide-binding oligomerization
      domain containing 2 (Nod2) receptor and downstream pathway in response to initial
      S. aureus biofilm infection. METHODS: Using a validated protocol, sinonasal
      mucosae from 4 non-CRS donors were cultured with and without S. aureus biofilms
      and planktonic cells. After 24 hours, RNA was extracted and gene expression was
      analyzed using a human antibacterial response polymerase chain reaction (PCR)
      array. Immunohistochemistry was performed to confirm the presence and determine
      the immunolocalization of selected proteins. RESULTS: C-X-C motif (CXC) chemokine
      ligands 1 and 2, interleukin-6 (IL-6), and genes related to the Nod2 pathway were
      significantly upregulated in biofilm-treated tissues compared with control
      samples. Nod2 pathway-specific gene expression was increased in biofilm-treated
      tissues compared with planktonic S. aureus-treated explants. Enhanced expression
      of Nod2 and nuclear factor kappa B1 (NF-kappaB1) was also detected with
      immunohistochemistry in control and biofilm-treated tissues. CONCLUSION: S.
      aureus biofilms exerted a proinflammatory response in the mucosa and activation
      of the Nod2 pathway, indicating this receptor to be involved in the innate immune
      response to S. aureus biofilms. Further studies are required to elucidate the
      role of this pathway in CRS.

PMID- 24039209
TI  - Chronic sleep fragmentation promotes obesity in young adult mice.
AB  - OBJECTIVES: Short sleep confers a higher risk of obesity in humans. Restricted
      sleep increases appetite, promotes higher calorie intake from fat and
      carbohydrate sources, and induces insulin resistance. However, the effects of
      fragmented sleep (SF), such as occurs in sleep apnea, on body weight, metabolic
      rates, and adipose tissue distribution are unknown. METHODS: C57BL/6 mice were
      exposed to SF for 8 weeks. Their body weight, food consumption, and metabolic
      expenditure were monitored over time, and their plasma leptin levels measured
      after exposure to SF for 1 day as well as for 2 weeks. In addition, adipose
      tissue distribution was assessed at the end of the SF exposure using MRI
      techniques. RESULTS: Chronic SF-induced obesogenic behaviors and increased weight
      gain in mice by promoting increased caloric intake without changing caloric
      expenditure. Plasma leptin levels initially decreased and subsequently increased.
      Furthermore, increases in both visceral and subcutaneous adipose tissue volumes
      occurred. CONCLUSIONS: These results suggest that SF, a frequent occurrence in
      many disorders and more specifically in sleep apnea, is a potent inducer of
      obesity via activation of obesogenic behaviors and possibly leptin resistance, in
      the absence of global changes in energy expenditure.

PMID- 24039210
TI  - Nanotubular assembly of amide dendron and cucurbiturils.

PMID- 24039213
TI  - Protective efficacy of sunglasses on the conjunctival symptoms of seasonal
      rhinitis.
AB  - BACKGROUND: Although allergen avoidance can lead to significant improvements in
      symptoms of allergic rhinitis, there are very few studies in this area.
      Sunglasses could be effective for protection of eyes from pollen as a cheap,
      comfortable, and simple avoidance option for allergens. The aim of this study is
      to determine if wearing sunglasses can decrease ocular symptoms. METHODS: Ocular
      symptomatic patients (39 total) who had a confirmed history of seasonal rhinitis
      by skin prick tests and negative skin prick tests for perennial allergens were
      included in the study. The duration of the study was 4 weeks with 3 required
      visits. At the onset of the 1-week run-in period, patients were randomized and
      divided into 2 groups. Group I (n = 18) received topical aqueous nasal budesonide
      regularly and loratadine once daily as a rescue medication. Group II (n = 21)
      wore sunglasses during daytime as an addition to this medication. Subjective data
      included a daily diary recording nasal and ocular symptom scores and
      antihistamine need during the study period. RESULTS: Sunglasses significantly
      reduced ocular symptoms (p = 0.002) and use of antihistamines (p = 0.009).
      CONCLUSION: Sunglasses are an inexpensive and simple treatment for patients with
      allergic conjunctivitis.

PMID- 24039219
TI  - Weight bias internalization, depression, and self-reported health among
      overweight binge eating disorder patients.
AB  - OBJECTIVE: This study aimed to examine the relationship between internalization
      of weight bias, which has been linked to specific negative mental health
      outcomes, and overall mental and physical health among overweight patients with
      binge eating disorder (BED). The role of depressive symptoms as a potential
      mediator in this relationship was also tested. METHODS: In a cross-sectional
      study, 255 individuals who were overweight and seeking treatment for BED
      completed the Weight Bias Internalization Scale (WBIS), Short-Form 36 Health
      Survey (SF-36), and Beck Depression Inventory-II (BDI). Regression analyses were
      conducted to evaluate the relationship between the WBIS and the SF-36, and
      bootstrapping mediation analyses were conducted to test whether BDI scores
      mediated this relationship. RESULTS: Higher weight bias internalization was
      associated with poorer self-reported health on all scales of the SF-36, and BDI
      scores mediated the relationship. Additional analyses revealed that WBIS scores
      also mediated the relationship between BDI scores and three SF-36 scales.
      CONCLUSIONS: Weight bias internalization is associated with poorer overall mental
      and physical health, and depressive symptoms may play a role in accounting for
      this relationship in treatment-seeking overweight patients with BED.

PMID- 24039220
TI  - "Safe Harbor": evaluation of a professionalism case discussion intervention for
      the gross anatomy course.
AB  - Medical professionalism is a multifaceted paradigm and is an essential component
      of medical education. Gross anatomy is a laboratory to teach professionalism, and
      promoting critical reflection in medical students is a prerequisite to furthering
      professionalism. The aim of this study was to determine if professionalism case
      discussions during a Gross Anatomy course improve students' reflections using a
      validated reflection instrument (12 items; five-point Likert scale where 1 =
      Disagree, 2 = Disagree with reservation, 3 = Neutral, 4 = Agree with reservation,
      5 = Agree). Four facilitated reflection sessions were aimed at fostering
      reflective capacity through reflection on elements of professionalism. Results
      did not show a significant change between pre-and postintervention reflection
      scores (3.45 +/- 0.61 vs. 3.48 +/- 0.51; P = 0.82). Historical control students
      were found to have significantly higher reflection scores when compared with
      postintervention students (3.91 +/- 0.53 vs. 3.48 +/- 0.51; P < 0.001). However,
      the historical control students were found to have significantly higher
      professionalism scores (P = 0.001) as compared with the intervention students.
      Student satisfaction was high, with 25 of 28 (89.2%) students reporting that the
      sessions should be included as a component of future anatomy courses. While
      reflection scores were not significantly increased as a result of the
      intervention, students expressed appreciation for the opportunity to discuss
      professionalism issues related to the dissection of cadavers. Additionally, the
      intervention students had both lower professionalism scores and lower reflection
      scores, which supports the idea that highly professional students are more
      capable of reflecting on professionalism. Future studies should determine whether
      this case discussion intervention improves objective measures of professionalism.

PMID- 24039221
TI  - Epidermal growth factor receptor, p16, cyclin D1, and p53 staining patterns for
      inverted papilloma.
AB  - BACKGROUND: The aim of this study was better characterize the staining patterns
      of inverted papilloma (IP) with and without carcinoma by performing
      immunohistochemistry for p16, epidermal growth factor receptor (EGFR), p53, and
      cyclin D1 antibodies in a large patient cohort. METHODS: A total of 162 IP
      specimens were collected from 147 patients treated at the University of Michigan
      between 1996 and 2011. Twenty-two specimens contained carcinoma. Tumor was
      extracted for construction of 2 tissue microarrays and stained for p16, EGFR,
      p53, and cyclin D1. Tumor staining intensity and percentage staining were scored.
      RESULTS: Benign disease was positive for p16 in 64%, EGFR in 50%, p53 in 30%, and
      cyclin D1 in 76%. IP with carcinomatous degeneration was positive for p16 in 14%,
      EGFR in 71%, p53 in 62%, and cyclin D1 in 76%. The differences in staining
      positivity between benign and malignant disease reached significance for p16 and
      p53 only. Mean percentage staining by tumor surface area for IP and IP with
      carcinoma was 12% vs 7% for p16 (no statistical significance [NS]), 20% vs 34%
      for EGFR (NS), 4% vs 24% for p53 (p < 0.001), and 17% vs 21% for cyclin D1 (NS).
      CONCLUSION: Important characteristic staining pattern for IP with and without
      carcinoma are highlighted in this study. Unlike recent trends in human papilloma
      virus (HPV)-related head and neck malignancies, low expression of p16 is a marker
      for malignancy in this series. Positive staining for p53 correlates with the
      development of carcinoma in IP.

PMID- 24039222
TI  - Postmortem lung volume/body weight standards for term and preterm infants.
AB  - Assessment of lung growth is a critical component of the perinatal autopsy.
      Increased lung liquid content may lead to overestimation of lung growth based on
      (wet) lung weight. In contrast, lung volume is not influenced by intraalveolar
      lung liquid. Our aim was to establish age-specific reference values for
      postmortem lung volume/BW in preterm and term infants. We performed a
      retrospective analysis of fetuses/infants (16-41 weeks' gestation) without (N =
      134) or with (N = 79) risk factors for pulmonary hypoplasia. Lungs were inflated
      at standardized pressure and volumes determined by water immersion method. Lung
      volume increased 11-fold between 16 and 41 weeks' gestation, concomitant with a
      16-fold increase in BW. Mean lung volume/BW remained constant at 33-34 ml/kg
      between 16 and 31 weeks' gestation and decreased to 23.4 ml/kg at term. Lung
      volume/BW of infants with severe risk factors (renal anomalies, diaphragmatic
      hernia) was significantly lower than age-matched standards. In this group, all
      fetuses/infants diagnosed as having lung hypoplasia by lung volume/BW also had
      lung hypoplasia LW/BW standards. However, in infants with "softer" risk factors
      (rupture of membranes, chromosomal anomalies), 5/26 cases diagnosed with lung
      hypoplasia based on lung volume/BW had normal LW/BW ratios. In these discrepant
      cases, lung sections showed significant inflammation and edema, likely accounting
      for increased wet lung weight. In conclusion, we determined age-specific lung
      volume/BW reference values for preterm and term infants. In selected situations
      assessment of lung volume/BW may represent a useful complementary tool to LW/BW
      for postmortem evaluation of lung size.

PMID- 24039223
TI  - Use of quantile regression to investigate the longitudinal association between
      physical activity and body mass index.
AB  - OBJECTIVE: To examine associations among age, physical activity (PA), and birth
      cohort on body mass index (BMI) percentiles in men. METHODS: Longitudinal
      analyses using quantile regression were conducted among men with >= two
      examinations between 1970 and 2006 from the Aerobics Center Longitudinal Study (n
      = 17,759). Height and weight were measured; men reported their PA and were
      categorized as inactive, moderately, or highly active at each visit. Analyses
      allowed for longitudinal changes in PA. RESULTS: BMI was greater in older than
      younger men and in those born in 1960 than those born in 1940. Inactive men
      gained weight significantly more rapidly than active men. At the 10th percentile,
      increases in BMI among inactive, moderately active, and highly active men were
      0.092, 0.078, and 0.069 kg/m(2) per year of age, respectively. The 10th
      percentile increased by 0.081 kg/m(2) per birth year and by 0.180 kg/m(2) at the
      90th percentile, controlling for age. CONCLUSION: Although BMI increased with
      age, PA reduced the magnitude of the gradient among active compared to inactive
      men. Regular PA had an important, protective effect against weight gain. This
      study provides evidence of the utility of quantile regression to examine the
      specific causes of the obesity epidemic.

PMID- 24039224
TI  - Group in-course assessment promotes cooperative learning and increases
      performance.
AB  - The authors describe and evaluate a method to motivate medical students to
      maximize the effectiveness of dissection opportunities by using In-Course
      Assessments (ICAs) to encourage teamwork. A student's final mark was derived by
      combining the group dissection mark, group mark for questions, and their
      individual question mark. An analysis of the impact of the ICA was performed by
      comparing end of module practical summative marks in student cohorts who had, or
      had not, participated in the ICAs. Summative marks were compared by two-way ANOVA
      followed by Dunnets test, or by repeated measures ANOVA, as appropriate. A cohort
      of medical students was selected that had experienced both practical classes
      without (year one) and with the new ICA structure (year two). Comparison of
      summative year one and year two marks illustrated an increased improvement in
      year two performance in this cohort. A significant increase was also noted when
      comparing this cohort with five preceding year two cohorts who had not
      experienced the ICAs (P <0.0001). To ensure that variation in the practical
      summative examination was not impacting on the data, a comparison was made
      between three cohorts who had performed the same summative examination. Results
      show that students who had undertook weekly ICAs showed significantly improved
      summative marks, compared with those who did not (P <0.0001). This approach to
      ICA promotes engagement with learning resources in an active, team-based,
      cooperative learning environment.

PMID- 24039225
TI  - Regional disparities and practice patterns in surgical approaches to pituitary
      tumors in the United States.
AB  - BACKGROUND: Traditional microscopic and endoscopic transsphenoidal approaches
      (TSAs) are the most common surgical techniques in pituitary surgery. Examining
      regional practice patterns in pituitary surgery can provide valuable insights
      into which surgical strategies are most accessible, effective, and cost
      efficient. In this study we investigated regional variations in surgical
      approaches to pituitary tumors and evaluated evolving practice patterns in
      pituitary surgery. METHODS: The 2010 Medicare Part B Carrier Summary Database and
      Medicare Part B National Summary Database from 2003-2010 were examined using
      pituitary surgery Current Procedure Terminology (CPT) codes 61548 (microscopic
      transsphenoidal approach), 62165 (endoscopic transsphenoidal approach), and 61546
      (transcranial approach). RESULTS: Endoscopic TSAs increased by over 10-fold in
      the past decade, while usage of microscopic TSAs decreased by 23.3%.
      Nevertheless, the microscopic approach was still the most common TSA (64.7%) in
      2010 compared to the endoscopic approach (35.3%). The microscopic TSA was
      predominant in the Southern and Western United States (74% and 69%,
      respectively). In the Northeast and Midwest, the rates of microscopic and
      endoscopic TSAs were roughly equivalent. However, the rate of endoscopic TSAs was
      statistically significantly higher (p < 0.05) in the Northeast and Midwest (47%
      and 45%, respectively) than in the South and West (26% and 31%, respectively).
      Transcranial approaches continued to decline from 4% to 2% over the last decade.
      CONCLUSION: Regional disparities in transsphenoidal practice patterns exist in
      the United States. Although the microscopic approach is still more common
      overall, there has been an evolving shift toward endoscopic TSAs in the last
      decade.

PMID- 24039226
TI  - Nebulizing poractant alfa versus conventional instillation: Ultrastructural
      appearance and preservation of surface activity.
AB  - BACKGROUND: Nebulized surfactant therapy has been proposed as an alternative
      method of surfactant administration. The use of a perforated vibrating membrane
      nebulizer provides a variety of advantages over conventional nebulizers. We
      investigated the molecular structure and integrity of poractant alfa pre- and
      post-nebulization. METHOD: Curosurf(r) was nebulized using an Investigational
      eFlow(r) Nebulizer System. Non-nebulized surfactant ("NN"), recollected
      surfactant droplets from nebulization through an endotracheal tube ("NT") and
      nebulization of surfactant directly onto a surface ("ND") were investigated by
      transmission electron microscopy. Biophysical characteristics were assessed by
      the Langmuir-Wilhelmy balance and the Captive Bubble Surfactometer. RESULTS:
      Volume densities of lamellar body-like forms (LBL) and multi-lamellar forms (ML)
      were high for "NN" and "NT" samples (38.8% vs. 47.7% for LBL and 58.2% vs. 47.8%
      for ML). In the "ND" sample, we found virtually no LBL's, ML's (72.6%) as well as
      uni-lamellar forms (16.4%) and a new structure, the "garland-like" forms (9.4%).
      Surface tension for "NN" and "NT" was 23.33 +/- 0.29 and 25.77 +/- 1.12 mN/m,
      respectively. Dynamic compression-expansion cycling minimum surface tensions were
      between 0.91 and 1.77 mN/m. CONCLUSION: The similarity of surfactant
      characteristics of nebulized surfactant via a tube and the non-nebulized
      surfactant suggests that vibrating membrane nebulizers are suitable for
      surfactant nebulization. Alterations in surfactant morphology and characteristics
      after nebulization were transient. A new structural subtype of surfactant was
      identified.

PMID- 24039227
TI  - Moonlight affects mRNA abundance of arylalkylamine N-acetyltransferase in the
      retina of a lunar-synchronized spawner, the goldlined spinefoot.
AB  - Melatonin synthesis in the pineal gland and retina shows a rhythmic fashion with
      high levels at night and is controlled by a rate-limiting enzyme, arylalkylamine
      N-acetyltransferase (AANAT). A previous study revealed that moonlight suppresses
      the plasma melatonin levels of the goldlined spinefoot (Siganus guttatus), which
      exhibits a lunar cycle in its reproductive activity and repeats gonadal
      development toward and spawning around the first quarter moon. Whether the retina
      of this species responds to moonlight is unknown. To clarify the photoperceptive
      ability of this species, we aimed to clone the full-length cDNA of Aanat1
      (sgAanat1) from the retina and examine its transcriptional pattern under several
      daylight and moonlight regimes. The full-length sgAanat1 cDNA (1,038 bp)
      contained a reading frame encoding a protein of 225 amino acids, which was highly
      homologous to AANAT1 of other teleosts. Reverse transcription-polymerase chain
      reaction (PCR) analysis revealed that among the tissues tested, sgAanat1
      fragments were expressed exclusively in the retina. Real-time quantitative PCR
      analysis revealed that sgAanat1 fluctuated with high abundance at night under
      light-dark cycle and at subjective night under constant darkness, but not under
      constant light. These results suggest that sgAanat1 is regulated by both the
      external light signal and internal clock system. The abundance of sgAanat1 in the
      retina was higher at the culmination time around new moon than full moon phase.
      Additionally, exposing fish to brightness around the full moon period suppressed
      sgAanat1 mRNA abundance. Thus, moonlight is perceived by fish and has an impact
      on melatonin fluctuation in the retina.

PMID- 24039228
TI  - Empathic responsiveness of children and adolescents with high-functioning autism
      spectrum disorder.
AB  - Previous studies have shown reduced empathic responsiveness to others' emotions
      in preschoolers with autism spectrum disorder (ASD) and an intellectual
      disability. However, age and intelligence may promote children's empathic
      responsiveness. Therefore, we examined the empathic responsiveness in normally
      intelligent school-aged children and adolescents with a clinical diagnosis of ASD
      (n = 151) and in a typically developing comparison group (n = 50), using
      structured observations and parent reports. Based on the observations,
      participants' responses to the emotional displays of an interviewer were
      surprisingly similar. However, compared with parents from the comparison group,
      parents of a child with ASD reported significantly fewer empathic responses,
      particularly when the child received a high score on the Autism Diagnostic
      Observation Schedule. Even though parents report a reduced empathic
      responsiveness in school-aged children and adolescents with ASD, it may be
      difficult to find these empathic limitations during brief observations in a
      structured setting.

PMID- 24039229
TI  - Aerosolized KL4 surfactant improves short-term survival and gas exchange in
      spontaneously breathing newborn pigs with hydrochloric acid-induced acute lung
      injury.
AB  - BACKGROUND: Surfactant therapy may be beneficial in acute lung injury (ALI). In
      spontaneously breathing newborn pigs with ALI supported with continuous positive
      airway pressure (CPAP), we evaluated the hypothesis that aerosolized KL4
      surfactant (AERO KL4 S) would provide a similar therapeutic effect as
      intratracheal KL4 surfactant (ETT KL4 S) when compared to controls. METHODS: We
      randomized pigs with HCl-induced ALI to: (1) 175 mg/kg KL4 surfactant via
      endotracheal tube (ETT); (2) AERO KL4 S (22.5 mg/min phospholipid) for 60 min via
      continuous positive airway pressure (CPAP); or (3) sham procedure on CPAP. We
      obtained physiologic data and arterial blood gases throughout the 3-hr study. At
      study end, lungs were excised for analysis of interleukin-8 (IL-8),
      myeloperoxidase (MPO) levels and histomorphometric data. RESULTS: Pigs treated
      with ETT KL4 S and AERO KL4 S had improved survival and sustained pO2 compared to
      controls. The AERO KL4 S group had higher pH compared to controls. Lung IL-8
      levels were lower in the AERO KL4 S group compared to controls. Histomorphometric
      analysis showed less hemorrhage in the ETT and AERO KL4 S groups compared to
      controls. The AERO KL4 S group had more open lung units per fixed-field than the
      ETT KL4 S or controls. CONCLUSIONS: AERO KL4 S produced similar improvements in
      survival, physiology, inflammatory markers, and morphology as ETT KL4 S in an ALI
      model.

PMID- 24039231
TI  - Changes in glucose and carnitine levels and their transporters in utero-tubal
      junction in relation to sperm storage in the vespertilionid bat, Scotophilus
      heathi.
AB  - Prolonged sperm storage over winter is a common feature of reproduction in some
      bats. In order to understand how sperm storage in the female genital tract of the
      vespertilionid bat, Scotophilus heathi (Greater yellow bat), is controlled, we
      compared concentrations of glucose and the fatty-acid carrier carnitine in the
      blood, and carnitine concentrations and levels of expression of the glucose
      transporters (GLUTs) and the carnitine transporter OCTN2 in the utero-tubal
      junction of females during non-storage (early winter) and sperm-storage periods
      (late winter-early spring). During the sperm-storage period (December-January)
      blood glucose concentrations declined, as did the expression of GLUT3 and GLUT5
      in the utero-tubal junction. At the same time there were increases in the
      concentration of carnitine, and expression of OCTN2 and hormone-sensitive lipase
      (HSL) in the utero-tubal junction. These results suggest that prolonged sperm
      storage is enhanced by decreased glucose availability but increased free fatty
      acid availability at the site of sperm storage. Increases in expression of GLUT4
      and GLUT8 in late winter suggest a role for these GLUTs in increasing sperm
      motility prior to fertilization.

PMID- 24039230
TI  - Chronic rhinosinusitis and sleep: a contemporary review.
AB  - BACKGROUND: Patients with chronic rhinosinusitis (CRS) exhibit centrally mediated
      behavioral changes commonly referred to as "sickness behavior." Sleep alteration
      is a component of sickness behavior which is estimated to affect up to 70 million
      patients annually. Patients with CRS have poor sleep quality, and little is known
      about the underlying etiology and pathophysiology. This narrative review aims to
      further organize and present the current knowledge associating sleep and CRS.
      METHODS: A literature search was conducted of the OVID MEDLINE database using key
      search words including: "chronic rhinosinusitis," "sleep," "sleep disorders," and
      "sleep dysfunction." Additional keywords "nasal obstruction," "nasal polyp," and
      "fatigue" were identified and used to further delineate relevant articles.
      RESULTS: The articles that specifically addressed sleep and CRS were dissected
      and presented as follows: (1) chronic rhinosinusitis and sleep; (2) chronic
      rhinosinusitis and fatigue; (3) chronic rhinosinusitis, nasal obstruction, and
      sleep; and (4) pathophysiology of sleep in chronic rhinosinusitis (cytokines in
      both sleep and chronic rhinosinusitis and their association to the neuroimmune
      biology of chronic rhinosinusitis). CONCLUSION: Patients with CRS have sleep
      dysfunction that is associated with their disease severity and overall quality of
      life. The etiology of sleep dysfunction in CRS is most likely multifactorial.
      Increasing evidence suggests sleep dysfunction in patients with CRS is partly due
      to the inflammatory disease process, and sleep physiology in patients with CRS
      may be actively regulated by the inflammatory component of the disease.

PMID- 24039233
TI  - Intolerability of cobalt salt as erythropoietic agent.
AB  - Unfair athletes seek ways to stimulate erythropoiesis, because the mass of
      haemoglobin is a critical factor in aerobic sports. Here, the potential misuse of
      cobalt deserves special attention. Cobalt ions (Co(2+) ) stabilize the hypoxia
      inducible transcription factors (HIFs) that increase the expression of the
      erythropoietin (Epo) gene. Co(2+) is orally active, easy to obtain, and
      inexpensive. However, its intake can bear risks to health. To elaborate this
      issue, a review of the pertinent literature was retrieved by a search with the
      keywords 'anaemia', 'cobalt', 'cobalt chloride', 'erythropoiesis',
      'erythropoietin', 'Epo', 'side-effects' and 'treatment', amongst others. In
      earlier years, cobalt chloride was administered at daily doses of 25 to 300 mg
      for use as an anti-anaemic agent. Co(2+) therapy proved effective in stimulating
      erythropoiesis in both non-renal and renal anaemia, yet there were also serious
      medical adverse effects. The intake of inorganic cobalt can cause severe organ
      damage, concerning primarily the gastrointestinal tract, the thyroid, the heart
      and the sensory systems. These insights should keep athletes off taking Co(2+) to
      stimulate erythropoiesis.

PMID- 24039232
TI  - Fibrillin-1 directly regulates osteoclast formation and function by a dual
      mechanism.
AB  - Mutations in the fibrillin-1 gene give rise to a number of heritable disorders,
      which are all characterized by various malformations of bone as well as
      manifestations in other tissues. However, the role of fibrillin-1 in the
      development and homeostasis of bone is not well understood. Here, we examined the
      role of fibrillin-1 in regulating osteoclast differentiation from primary bone
      marrow-derived precursors and monocytic RAW 264.7 cells. The soluble N-terminal
      half of fibrillin-1 (rFBN1-N) strongly inhibited osteoclastogenesis, whereas the
      C-terminal half (rFBN1-C) did not. By contrast, when rFBN1-N was immobilized on
      calcium phosphate, it did not affect osteoclastogenesis but modulated osteoclast
      resorptive activity, which was evident by a larger number of smaller resorption
      pits. Using a panel of recombinant sub-fragments spanning rFBN1-N, we localized
      an osteoclast inhibitory activity to the 63 kDa subfragment rF23 comprising the N
      terminal region of fibrillin-1. Osteoclastic resorption led to the generation of
      small fibrillin-1 fragments that were similar to those identified in human
      vertebral bone extracts. rF23, but not rFBN1-N, was found to inhibit the
      expression of cathepsin K, matrix metalloproteinase 9 and Dcstamp in
      differentiating osteoclasts. rFBN1-N, but not rF23, exhibited interaction with
      RANKL. Excess RANKL rescued the inhibition of osteoclastogenesis by rFBN1-N. By
      contrast, rF23 disrupted RANKL-induced Ca(2+) signaling and activation of
      transcription factor NFATc1. These studies highlight a direct dual inhibitory
      role of N-terminal fibrillin-1 fragments in osteoclastogenesis, the sequestration
      of RANKL and the inhibition of NFATc1 signaling, demonstrating that osteoclastic
      degradation of fibrillin-1 provides a potent negative feedback that limits
      osteoclast formation and function.

PMID- 24039234
TI  - Impact assessment of a decision rule for using antibiotics in pneumonia: a
      randomized trial.
AB  - BACKGROUND: Although more than half of the cases of pneumonia in children can be
      due to virus, most of them receive antibiotic treatment. A previously published
      clinical prediction rule bacterial pneumonia score (BPS) allows the
      identification of children with pneumonia who do not require antibiotics, but its
      impact has not been evaluated. We assessed whether the use of the BPS for the
      initial management of patients with pneumonia results in decreasing the use of
      antibiotics than under standard management of this condition without increasing
      patients' risks. METHODS: This was a randomized, parallel-group, observer-blind,
      controlled clinical trial comparing the use of antibiotics in children aged 3-60
      months treated for pneumonia in an outpatient setting, according to two methods
      of initial management. Patients were assigned randomly to management according to
      the BPS (antibiotic indication with a BPS >= 4 points) or routine management
      (antibiotic indication based on the institutional guidelines). We calculated the
      proportion of the use of antibiotics in each group and evaluated each patient's
      clinical outcome. RESULTS: We included 120 patients (60 BPS and 60 controls) with
      a mean age of 24.2 +/- 14.1 months. The use of antibiotics was significantly
      lower in the BPS group (46.6% vs. 86.6; OR 0.13; 95% CI: 0.05-0.35; P < 0.001).
      We observed an unfavorable outcome in 10 patients (8.3%), 5 in each group (P =
      1.0; OR: 1.0 95% CI: 0.2-3.6). CONCLUSION: The use of antibiotics was
      significantly lower in the group managed according to the BPS compared to the
      conventionally treated group, without increasing the rate of treatment failure.

PMID- 24039235
TI  - Caspase 3 in molluscan tissues: localization and possible function.
AB  - The presence and localization of caspase 3, a master enzyme in apoptosis, have
      been analyzed in tissues of four species of Molluscs: the Bivalves Callista
      chione and Adamussium colbecki and the Gastropods Helix pomatia and Neobuccinum
      eatoni. Western blotting and immunocytochemical analyses show that a 32 kDa
      caspase 3 is present in guts, in gill lamellae and in digestive glands during
      digestion but not in heart tissue or in resting digestive glands. The enzyme is
      also found in gonads of both sexes but there are significant differences between
      Bivalves and Gastropods and between male and female germ cells, especially in
      late stages of differentiation. In particular, caspase 3 is abundant in Bivalves
      oocytes and in Gastropods spermatozoa but not in Gastropods oocytes; in Callista
      spermatozoa it appears only after sea water activation. TUNEL staining and PCNA
      immunolocalization, carried out on C. chione and H. pomatia tissues, suggest that
      caspase 3 is primarily associated with degenerative processes in gut, digestive
      gland and early stage germ cells while in gills, oocytes and mature spermatozoa
      it is primarily correlated with cell function and/or differentiation.

PMID- 24039237
TI  - Comparison of drug concentrations between whole blood and oral fluid.
AB  - The relationship of drug concentrations between oral fluid and whole blood was
      evaluated by studying the linear correlation of concentrations and calculating
      the oral fluid to blood concentration ratios (OF/B) for different substances.
      Paired oral fluid and whole blood samples were collected from volunteers and
      persons suspected of drug use in four European countries. Oral fluid samples were
      collected with the Saliva?SamplerTM device. All samples were analyzed for drugs
      of abuse and psychoactive medicines with validated gas and liquid chromatography
      mass spectrometric methods. The median OF/B ratios were, for amphetamines 19-22,
      for opioids 1.8-11, for cocaine and metabolites 1.7-17, for tetrahydrocannabinol
      (THC) 14, for benzodiazepines 0.035-0.33, and for other psychoactive medicines
      0.24-3.7. Most of the these results were close to theoretical values based on the
      physicochemical properties of the drugs and to values presented earlier, but
      there was a lot of inter-individual variation in the OF/B ratios. For all
      substances, except for lorazepam (R(2)  = 0.031) and THC (R(2)  = 0.030), a
      correlation between the oral fluid and whole blood concentrations was observed.
      Due to large variation seen here, drug findings in oral fluid should not be used
      to estimate the corresponding concentrations in whole blood (or vice versa).
      However, detection of drugs in oral fluid is a sign of recent drug use and oral
      fluid can be used for qualitative detection of several drugs, e.g. in
      epidemiological prevalence studies. By optimizing the sampling and the analytical
      cut-offs, the potential of oral fluid as a confirmation matrix could be enhanced.

PMID- 24039236
TI  - Nitrogen regulation of protein-protein interactions and transcript levels of GlnK
      PII regulator and AmtB ammonium transporter homologs in Archaea.
AB  - Gene homologs of GlnK PII regulators and AmtB-type ammonium transporters are
      often paired on prokaryotic genomes, suggesting these proteins share an ancient
      functional relationship. Here, we demonstrate for the first time in Archaea that
      GlnK associates with AmtB in membrane fractions after ammonium shock, thus,
      providing a further insight into GlnK-AmtB as an ancient nitrogen sensor pair.
      For this work, Haloferax mediterranei was advanced for study through the
      generation of a pyrE2-based counterselection system that was used for targeted
      gene deletion and expression of Flag-tagged proteins from their native promoters.
      AmtB1-Flag was detected in membrane fractions of cells grown on nitrate and was
      found to coimmunoprecipitate with GlnK after ammonium shock. Thus, in analogy to
      bacteria, the archaeal GlnK PII may block the AmtB1 ammonium transporter under
      nitrogen-rich conditions. In addition to this regulated protein-protein
      interaction, the archaeal amtB-glnK gene pairs were found to be highly regulated
      by nitrogen availability with transcript levels high under conditions of nitrogen
      limitation and low during nitrogen excess. While transcript levels of glnK-amtB
      are similarly regulated by nitrogen availability in bacteria, transcriptional
      regulators of the bacterial glnK promoter including activation by the two
      component signal transduction proteins NtrC (GlnG, NRI) and NtrB (GlnL, NRII) and
      sigma factor sigma(N) (sigma(54) ) are not conserved in archaea suggesting a
      novel mechanism of transcriptional control.

PMID- 24039238
TI  - Comparison of conventional pulmonary rehabilitation and high-frequency chest wall
      oscillation in primary ciliary dyskinesia.
AB  - BACKGROUND: Enhancement of mucociliary clearance by pulmonary rehabilitation (PR)
      is advocated in primary ciliary dyskinesia (PCD). Our primary aim was to compare
      the efficacy and safety of postural drainage, percussion and vibration
      [conventional PR (CPR)], and high frequency chest wall oscillation (HFCWO) by
      studying change in pulmonary function. Our secondary aim was to evaluate patient
      preferences regarding the two methods. METHODS: This was a controlled randomized
      crossover study. PCD patients between the ages of 7 and 18 years were assigned to
      two groups, first group performed airway clearance with CPR at hospital for 5
      days and after a 2-day washout period HFCWO was applied to the same group at
      home. HFCWO was applied first to the other group and then these patients were
      hospitalized for CPR. The primary outcome measure of the study was pulmonary
      function test (PFT). The secondary outcomes were pulse arterial oxygen saturation
      (SpO2 ) and the perceived efficiency and comfort level. RESULTS: PFT values of
      patients increased significantly after both PR methods (before/after): CPR: FVC:
      77.0 +/- 14.1/81.8 +/- 13.0 (P = 0.002); FEV1 : 72.9 +/- 14.8/78.7 +/- 13.5 (P =
      0.001); PEF: 73.8 +/- 14.5/82.5 +/- 14.5 (P = 0.001); FEF25-75 : 68.6 +/-
      27.6/74.9 +/- 29.3 (P = 0.007). HFCWO FVC: 75.1 +/- 15.3/80.3 +/- 13.9 (P =
      0.002); FEV1 : 71.4 +/- 16/77.4 +/- 14.6 (P = 0.001); PEF: 70.9 +/- 18.0/78.3 +/-
      17.7 (P = 0.002); FEF25-75 : 70.5 +/- 23.4/76.4 +/- 25.6 (P = 0.006). There were
      no significant differences in % predicted FVC, FEV1 , PEF, and FEF25-75 increased
      values with CPR and HFCWO. HFCWO was found more comfortable (P = 0.04). Two PR
      methods were found efficient and no desaturation occurred during PR. CONCLUSIONS:
      PFTs were significantly increased after both PR methods. There were no
      differences in PFTs and SpO2 between the CPR and HFCWO groups. Both PR methods
      were found efficient. HFCWO was found more comfortable. HFCWO may be an option in
      patients with chronic pulmonary disease and low adherence to PR.

PMID- 24039239
TI  - Estrogen favors the differentiation of ovarian tissues in the ambisexual gonads
      of anemonefish Amphiprion clarkii.
AB  - All undifferentiated gonads of anemonefish first differentiate into ovaries, and
      then testicular tissue appear among ovarian tissue, and finally form ambisexual
      gonads with both ovarian and testicular tissues. The role of estradiol-17beta
      (E2) in differentiation of ovarian cells is well conserved across phyla; however,
      its role in development of ambisexual gonads is poorly understood. Here we
      demonstrate that the E2 produced during the differentiation of ovarian cells does
      not allow testicular cells to differentiate in the prospective ambisexual gonad.
      We examined the immunolocalization of the steroidogenic enzyme cytochrome
      aromatase (P450(arom)), which is involved in E2 production. In the gonads,
      numbers of the P450(arom) -positive cells increased during ovarian
      differentiation. However, immunopositive cells with weak signal intensity were
      seen in the interstitial areas among oocytes and between oocytes and testicular
      tissue undergoing testicular differentiation. In contrast, P450(arom) -positive
      cells were not found in any testicular tissues of the ambisexual gonads. We also
      examined changes in E2 production in vitro in the gonads during testicular
      differentiation. E2 was high in the ovaries before the appearance all of
      testicular tissue, and decreased accompanying the differentiation of testicular
      tissue. These results suggest a balance of estrogen/androgen seems to be
      important during sex differentiation, and then a shift from estrogen to androgen
      production may induce testicular differentiation in the ovary. Further, exogenous
      E2 treatment suppressed naturally occurring differentiation of testicular cells
      forming exclusively ovarian tissues in the gonad in vivo, suggesting the increase
      of estrogen blocks the differentiation of testicular tissue and the formation of
      ambisexual gonad.

PMID- 24039241
TI  - Innovative interventions in pediatric obesity: commentary and future directions.

PMID- 24039240
TI  - Immunity protein release from a cell-bound nuclease colicin complex requires
      global conformational rearrangement.
AB  - Nuclease colicins bind their target receptor BtuB in the outer membrane of
      sensitive Escherichia coli cells in the form of a high-affinity complex with
      their cognate immunity proteins. The release of the immunity protein from the
      colicin complex is a prerequisite for cell entry of the colicin and occurs via a
      process that is still relatively poorly understood. We have previously shown that
      an energy input in the form of the cytoplasmic membrane proton motive force is
      required to promote immunity protein (Im9) release from the colicin E9/Im9
      complex and colicin cell entry. We report here that engineering rigidity in the
      structured part of the colicin translocation domain via the introduction of
      disulfide bonds prevents immunity protein release from the colicin complex.
      Reduction of the disulfide bond by the addition of DTT leads to immunity protein
      release and resumption of activity. Similarly, the introduction of a disulfide
      bond in the DNase domain previously shown to abolish channel formation in planar
      bilayers also prevented immunity protein release. Importantly, all disulfide
      bonds, in the translocation as well as the DNase domain, also abolished the
      biological activity of the Im9-free colicin E9, the reduction of which led to a
      resumption of activity. Our results show, for the first time, that conformational
      flexibility in the structured translocation and DNase domains of a nuclease
      colicin is essential for immunity protein release, providing further evidence for
      the hypothesis that global structural rearrangement of the colicin molecule is
      required for disassembly of this high-affinity toxin-immunity protein complex
      prior to outer membrane translocation.

PMID- 24039242
TI  - Kinematics of ribbon-fin locomotion in the bowfin, Amia calva.
AB  - An elongated dorsal and/or anal ribbon-fin to produce forward and backward
      propulsion has independently evolved in several groups of fishes. In these
      fishes, fin ray movements along the fin generate a series of waves that drive
      propulsion. There are no published data on the use of the dorsal ribbon-fin in
      the basal freshwater bowfin, Amia calva. In this study, frequency, amplitude,
      wavelength, and wave speed along the fin were measured in Amia swimming at
      different speeds (up to 1.0 body length/sec) to understand how the ribbon-fin
      generates propulsion. These wave properties were analyzed to (1) determine
      whether regional specialization occurs along the ribbon-fin, and (2) to reveal
      how the undulatory waves are used to control swimming speed. Wave properties were
      also compared between swimming with sole use of the ribbon-fin, and swimming with
      simultaneous use of the ribbon and pectoral fins. Statistical analysis of ribbon
      fin kinematics revealed no differences in kinematic patterns along the ribbon
      fin, and that forward propulsive speed in Amia is controlled by the frequency of
      the wave in the ribbon-fin, irrespective of the contribution of the pectoral fin.
      This study is the first kinematic analysis of the ribbon-fin in a basal fish and
      the model species for Amiiform locomotion, providing a basis for understanding
      ribbon-fin locomotion among a broad range of teleosts.

PMID- 24039244
TI  - Achromobacter xylosoxidans induced bronchiolitis obliterans in cystic fibrosis.
AB  - We report a 12-year-old boy with progressive bronchiolitis obliterans caused by
      Achromobacter xylosoxidans (Ax) colonization after liver transplantation,
      resulting in a steep decline in lung function.

PMID- 24039243
TI  - The cytoplasmic PASC domain of the sensor kinase DcuS of Escherichia coli: role
      in signal transduction, dimer formation, and DctA interaction.
AB  - The cytoplasmic PASC domain of the fumarate responsive sensor kinase DcuS of
      Escherichia coli links the transmembrane to the kinase domain. PASC is also
      required for interaction with the transporter DctA serving as a cosensor of DcuS.
      Earlier studies suggested that PASC functions as a hinge and transmits the signal
      to the kinase. Reorganizing the PASC dimer interaction and, independently,
      removal of DctA, converts DcuS to the constitutive ON state (active without
      fumarate stimulation). ON mutants were categorized with respect to these two
      biophysical interactions and the functional state of DcuS: type I-ON mutations
      grossly reorganize the homodimer, and decrease interaction with DctA. Type IIA-ON
      mutations create the ON state without grossly reorganizing the homodimer, whereas
      interaction with DctA is decreased. The type IIB-ON mutations were neither in
      PASC /PASC , nor in DctA/DcuS interaction affected, similar to fumarate activated
      wild-typic DcuS. OFF mutations never affected dimer stability. The ON mutations
      provide novel mechanistic insight: PASC dimerization is essential to silence the
      kinase. Reorganizing the homodimer and its interaction with DctA activate the
      kinase. The study suggests a novel ON homo-dimer conformation (type IIB) and an
      OFF conformation for PASC . Type IIB-ON corresponds to the fumarate induced wild
      type conformation, representing an interesting target for structural biology. 

PMID- 24039245
TI  - The human kinesin-14 HSET tracks the tips of growing microtubules in vitro.
AB  - Tip-tracking of kinesin-14 motor proteins is believed to be crucial for the
      assembly and maintenance of dynamic microtubule arrays. However, in contrast to
      other members of the kinesin-14 family, H. sapiens kinesin-14 HSET has so far
      never been observed to be prominently located at microtubule plus ends. Here,
      using an in vitro microtubule dynamics reconstitution assay we observe tip
      tracking of GFP-HSET in the presence of H. sapiens EB1 (hsEB1). Tip-tracking
      depended on the SxIP-like motif in HSET as well as on the EB homology domain in
      hsEB1. D. melanogaster Ncd and S. pombe Klp2 tip-tracking reconstitution assays
      accompanied by kinesin-14 amino acid sequence comparisons suggest that SxIP-like
      motif mediated tip-tracking dependent on EB family proteins is conserved in the
      kinesin-14 family of molecular motors.

PMID- 24039246
TI  - The delta-opioid receptor is sufficient, but not necessary, for spinal opioid
      adrenergic analgesic synergy.
AB  - Spinal administration of opioid and alpha2-adrenergic receptor (alpha2AR)
      agonists produces analgesia, and agonists interact synergistically when
      coadministered. The molecular mechanism underlying this synergy is largely
      unknown. Pharmacological studies have identified both the delta and the mu-opioid
      receptors (DOR and MOR) as candidate receptors capable of interacting
      synergistically with alpha2AR agonists. However, recent studies attribute the
      antinociceptive effect of DOR agonists to actions at the MOR, calling the role of
      DOR in opioid-adrenergic synergy into question. Other studies suggesting that DOR
      is implicated in morphine antinociception raise the possibility that DOR is
      nonetheless required for morphine synergy with alpha2AR agonists. This study
      aimed to determine whether DOR activation is sufficient and necessary to mediate
      opioid-adrenergic synergistic interactions in the spinal cord. The
      antinociceptive effects of clonidine, [D-Ala(2)]-deltorphin II (DeltII),
      morphine, and [D-Ala(2), N-Me-Phe(4), Gly-ol(5)]-enkephalin (DAMGO) were
      evaluated using the substance P (SP) behavioral assay in wild type (WT) and DOR
      knockout (KO) mice. Opioid-adrenergic drug interactions were evaluated after
      spinal coadministration of clonidine with DeltII, morphine, or DAMGO.
      Isobolographic analyses of dose-response curves determined whether interactions
      were synergistic or additive. The absence of DeltII antinociceptive efficacy in
      DOR-KO confirmed its selectivity in the SP assay. Although DeltII+clonidine
      interacted synergistically in WT mice, no interaction with clonidine was observed
      in DOR-KO mice. Clonidine was synergistic with morphine in both mouse strains.
      DAMGO did not synergize with clonidine in either strain. These findings confirm
      that although other opioid receptors can interact synergistically with alpha2AR
      agonists, DOR is sufficient for spinal opioid-adrenergic interactions.

PMID- 24039247
TI  - Screen time behaviours may interact with obesity genes, independent of physical
      activity, to influence adolescent BMI in an ethnically diverse cohort.
AB  - BACKGROUND: There has been little investigation of gene-by-environment
      interactions related to sedentary behaviour, a risk factor for obesity defined as
      leisure screen time (ST; i.e. television, video and computer games). OBJECTIVE:
      To test the hypothesis that limiting ST use attenuates the genetic predisposition
      to increased body mass index (BMI), independent of physical activity. DESIGN:
      Using 7642 wave II participants of the National Longitudinal Study of Adolescent
      Health, (Add Health; mean = 16.4 years, 52.6% female), we assessed the
      interaction of ST (h week(-1) ) and 41 established obesity single nucleotide
      polymorphisms (SNPs) with age- and sex-specific BMI Z-scores in 4788 European
      American (EA), 1612 African-American (AA) and 1242 Hispanic American (HA)
      adolescents. RESULTS: Nominally significant SNP*ST interaction were found for
      FLJ35779 in EA, GNPDA2 in AA and none in HA (EA: beta [SE] = 0.016[0.007]), AA:
      beta [SE] = 0.016[0.011]) per 7 h week(-1) ST and one risk allele in relation to
      BMI Z-score. CONCLUSIONS: While for two established BMI loci, we find evidence
      that high levels of ST exacerbate the influence of obesity susceptibility
      variants on body mass; overall, we do not find strong evidence for interactions
      between the majority of established obesity loci. However, future studies with
      larger sample sizes, or that may build on our current study and the growing
      published literature, are clearly warranted.

PMID- 24039248
TI  - Useful marker of oscillatory lung function in methacholine challenge test
      comparison of reactance and resistance with dose-response slope.
AB  - BACKGROUND: There are few studies focusing on the comparison of resistance (Rrs)
      and reactance (Xrs) in impulse oscillometry system (IOS) in the bronchial
      challenge test using dose-response slope (DRS), a quantitative index of bronchial
      hyperresponsiveness. MATERIAL AND METHODS: We conducted a case-control study of
      144 asthmatic and 218 non-asthmatic children to compare the diagnostic accuracy
      of two-point linear DRS for FEV1 , Rrs5 , and Xrs5 (DRS_FEV1 , DRS_Rrs5 , and
      DRS_Xrs5 ) and assessed various diagnostic cut-off points of provocation
      concentrations (PC) using receiver operating characteristic (ROC) curves.
      RESULTS: DRS_FEV1 had a stronger correlation with DRS_Xrs5 (r = 0.739, P < 0.001)
      than with DRS_Rrs5 (r = 0.652, P < 0.001) and the area under the ROC curves of
      DRS_Xrs5 (0.737) was similar to that of DRS_FEV1 (0.732) and higher than that of
      DRS_Rrs5 (0.668). The area under the ROC curves in order of greater value was as
      follows: absolute change of Xrs5 (Abs_Xrs5 ) (0.759) > percent change of FEV1
      (Pch_FEV1 ) (0.735) > Pch_Xrs5 (0.727) > Abs_Rrs5 (0.690) > Pch_Rrs5 (0.630).
      PC78 _Xrs5 and PC0.17 _Xrs5 of IOS showed considerably good sensitivity and
      specificity comparable to those of PC20 _FEV1 by spirometry. Additional 18 (13%)
      children who showed normal spirometric measures were identified as asthmatics
      with the use of IOS. CONCLUSION: The utility of the DRS_Xrs5 to differentiate
      asthmatics from controls was comparable to that of the DRS_FEV1 and better than
      that of the DRS_Rrs5 . In addition, IOS could detect additional asthmatic
      patients who did not show positive responses in spirometry.

PMID- 24039249
TI  - Heat-shock protein 70 binds microtubules and interacts with kinesin in tobacco
      pollen tubes.
AB  - The heat-shock proteins of 70 kDa are a family of ubiquitously expressed proteins
      important for protein folding. Heat-shock protein 70 assists other nascent
      proteins to achieve the spatial structure and ultimately helps the cell to
      protect against stress factors, such as heat. These proteins are localized in
      different cellular compartments and are associated with the cytoskeleton. We
      identified a heat-shock protein 70 isoform in the pollen tube of tobacco that
      binds to microtubules in an ATP-dependent manner. The heat-shock protein 70 was
      identified as part of the so-called ATP-MAP (ATP-dependent microtubule-associated
      protein) fraction, which also includes the 90-kDa kinesin, a mitochondria
      associated motor protein. The identity of heat-shock protein 70 was validated by
      immunological assays and mass spectrometry. Sequence analysis showed that this
      heat-shock protein 70 is more similar to specific heat-shock proteins of
      Arabidopsis than to corresponding proteins of tobacco. Two-dimensional
      electrophoresis indicated that this heat-shock protein 70 isoform only is part of
      the ATP-MAP fraction and that is associated with the mitochondria of pollen
      tubes. Sedimentation assays showed that the binding of heat-shock protein 70 to
      microtubules is not affected by AMPPNP but it increases in the presence of the 90
      kDa kinesin. Binding of heat-shock protein 70 to microtubules occurs only
      partially in the presence of ATP but it does not occur if, in addition to ATP,
      the 90-kDa kinesin is also present. Data suggest that the binding (but not the
      release) of heat-shock protein 70 to microtubules is facilitated by the 90-kDa
      kinesin.

PMID- 24039250
TI  - Obstructive sleep apnea in infancy: a 7-year experience at a pediatric sleep
      center.
AB  - PURPOSE: To investigate the common indications for polysomnogram (PSG) associated
      co-morbid conditions, evaluation strategies, treatment options, and outcomes in a
      series of infants diagnosed with obstructive sleep apnea (OSA) by a PSG. METHODS:
      Retrospective chart review of infants who underwent PSG over a 7-year period was
      done. Infants with PSG diagnosed OSA were included in this study. RESULTS: A
      total of 97 infants (59 males, mean age 4.6 months, standard deviation 3.3
      months) were diagnosed with OSA (AHI >= 1/hr) based on PSG. The most common
      indication for PSG in infants were excessive snoring (53%) followed by nocturnal
      desaturations (24%). Associated co-morbid conditions included gastro-esophageal
      reflux (30%), laryngomalacia (24%), and craniofacial abnormalities (16%). Genetic
      abnormalities were found in 53%, of which trisomy 21 was the most common.
      Surgical treatments were employed in 36% and oxygen therapy in 15%. Thirty-eight
      patients were followed up with a repeat sleep study after a median interval of 8
      months (range 1-24 months), of whom 26/38 had resolution of symptoms. Twenty
      seven patients (28%) were followed clinically after a mean interval of 5 months
      of intervention (range, 1-34.5 months), in whom the symptoms resolved in 23/27
      patients. Seven patients were deceased at review. Causes of death included status
      epilepticus, respiratory failure, hepatic failure, kidney failure, or unknown
      causes. CONCLUSION: The etiologies of OSA in infants are different when compared
      to older children. PSG is feasible and a valuable tool in the diagnosis of OSA in
      infants and may help determine timely and appropriate evaluation and
      interventions. Clinical improvement in symptoms and resolution of PSG parameters
      were noted following medical and/or surgical interventions. Prospective studies
      need to be done to ascertain the long-term outcome of infants diagnosed with OSA
      to assess the benefits of early intervention on their neurocognitive development.

PMID- 24039251
TI  - SIRT1 redresses the imbalance of tissue inhibitor of matrix metalloproteinase-1
      and matrix metalloproteinase-9 in the development of mouse emphysema and human
      COPD.
AB  - Sirtuin1 (SIRT1), a protein/histone deacetylase, protects against the development
      of pulmonary emphysema. However, the molecular mechanisms underlying this
      observation remain elusive. The imbalance of tissue inhibitor of matrix
      metalloproteinases (TIMPs)/matrix metalloproteinases (MMPs) plays an important
      role in the pathogenesis of chronic obstructive pulmonary disease
      (COPD)/emphysema. We hypothesized that SIRT1 protects against emphysema by
      redressing the imbalance between MMPs and TIMPs. To test this hypothesis, SIRT1
      deficient and overexpressing/transgenic mice were exposed to cigarette smoke
      (CS). The protein level and activity of MMP-9 were increased in lungs of SIRT1
      deficient mice exposed to CS compared with wild-type (WT) littermates, and these
      effects were attenuated by SIRT1 overexpression. SIRT1 deficiency decreased the
      level of TIMP-1, which was augmented in SIRT1 transgenic mice compared with WT
      littermates by CS. However, the level of MMP-2, MMP-12, TIMP-2, TIMP-3, or TIMP-4
      was not altered by SIRT1 in response to CS exposure. SIRT1 reduction was
      associated with imbalance of TIMP-1 and MMP-9 in lungs of smokers and COPD
      patients. Mass spectrometry and immunoprecipitation analyses revealed that TIMP-1
      acetylation on specific lysine residues was increased, whereas its interaction
      with SIRT1 and MMP-9 was reduced in mouse lungs with emphysema, as well as in
      lungs of smokers and COPD patients. SIRT1 deficiency increased CS-induced TIMP-1
      acetylation, and these effects were attenuated by SIRT1 overexpression. These
      results suggest that SIRT1 protects against COPD/emphysema, in part, via
      redressing the TIMP-1/MMP-9 imbalance involving TIMP-1 deacetylation. Thus
      redressing the TIMP-1/MMP-9 imbalance by pharmacological activation of SIRT1 is
      an attractive approach in the intervention of COPD. 

PMID- 24039252
TI  - Targeting CD162 protects against streptococcal M1 protein-evoked neutrophil
      recruitment and lung injury.
AB  - Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock
      syndrome and acute lung damage. CD162 is an adhesion molecule that has been
      reported to mediate neutrophil recruitment in acute inflammatory reactions. In
      this study, the purpose was to investigate the role of CD162 in M1 protein
      provoked lung injury. Male C57BL/6 mice were treated with monoclonal antibody
      directed against CD162 or a control antibody before M1 protein challenge. Edema,
      neutrophil infiltration, and CXC chemokines were determined in the lung, 4 h
      after M1 protein administration. Fluorescence intravital microscopy was used to
      analyze leukocyte-endothelium interactions in the pulmonary microcirculation.
      Inhibition of CD162 reduced M1 protein-provoked accumulation of neutrophils,
      edema, and CXC chemokine formation in the lung by >54%. Moreover,
      immunoneutralization of CD162 abolished leukocyte rolling and firm adhesion in
      pulmonary venules of M1 protein-treated animals. In addition, inhibition of CD162
      decreased M1 protein-induced capillary trapping of leukocytes in the lung
      microvasculature and improved microvascular perfusion in the lungs of M1 protein
      treated animals. Our findings suggest that CD162 plays an important role in M1
      protein-induced lung damage by regulating leukocyte rolling in pulmonary venules.
      Consequently, inhibition of CD162 attenuates M1 protein-evoked leukocyte adhesion
      and extravasation in the lung. Thus, our results suggest that targeting the CD162
      might pave the way for novel opportunities to protect against pulmonary damage in
      streptococcal infections.

PMID- 24039254
TI  - Hallmarks in the study of respiratory physiology and the crucial role of Antoine
      Laurent de Lavoisier (1743-1794).
AB  - From the early 17th century the advent of physical and chemical sciences
      developed two important movements toward the explanation of all vital phenomena:
      the Iatrochemical and Iatromechanical Schools. The important research of their
      representatives such as Jan Baptist van Helmont, John Mayow, Robert Boyle, Gian
      Alfonso Borelli, Richard Lower, and Albrecht von Haller, followed by the
      discovery of the atmospheric gases, provided a fecund soil for the leading work
      of Lavoisier in respiratory physiology. 

PMID- 24039253
TI  - Thrombin selectively engages LIM kinase 1 and slingshot-1L phosphatase to
      regulate NF-kappaB activation and endothelial cell inflammation.
AB  - Endothelial cell (EC) inflammation is a central event in the pathogenesis of many
      pulmonary diseases such as acute lung injury and its more severe form acute
      respiratory distress syndrome. Alterations in actin cytoskeleton are shown to be
      crucial for NF-kappaB regulation and EC inflammation. Previously, we have
      described a role of actin binding protein cofilin in mediating cytoskeletal
      alterations essential for NF-kappaB activation and EC inflammation. The present
      study describes a dynamic mechanism in which LIM kinase 1 (LIMK1), a cofilin
      kinase, and slingshot-1Long (SSH-1L), a cofilin phosphatase, are engaged by
      procoagulant and proinflammatory mediator thrombin to regulate these responses.
      Our data show that knockdown of LIMK1 destabilizes whereas knockdown of SSH-1L
      stabilizes the actin filaments through modulation of cofilin phosphorylation;
      however, in either case thrombin-induced NF-kappaB activity and expression of its
      target genes (ICAM-1 and VCAM-1) is inhibited. Further mechanistic analyses
      reveal that knockdown of LIMK1 or SSH-1L each attenuates nuclear translocation
      and thereby DNA binding of RelA/p65. In addition, LIMK1 or SSH-1L depletion
      inhibited RelA/p65 phosphorylation at Ser(536), a critical event conferring
      transcriptional competency to the bound NF-kappaB. However, unlike SSH-1L, LIMK1
      knockdown also impairs the release of RelA/p65 by blocking IKKbeta-dependent
      phosphorylation/degradation of IkappaBalpha. Interestingly, LIMK1 or SSH-1L
      depletion failed to inhibit TNF-alpha-induced RelA/p65 nuclear translocation and
      proinflammatory gene expression. Thus this study provides evidence for a novel
      role of LIMK1 and SSH-1L in selectively regulating EC inflammation associated
      with intravascular coagulation. 

PMID- 24039256
TI  - Cycloheximide and lipopolysaccharide downregulate alphaENaC mRNA via different
      mechanisms in alveolar epithelial cells.
AB  - Active Na(+) transport mediated by epithelial Na(+) channel (ENaC) is vital for
      fetal lung fluid reabsorption at birth and pulmonary edema resolution.
      Previously, we demonstrated that alphaENaC expression and activity are
      downregulated in alveolar epithelial cells by cycloheximide (Chx) and Pseudomonas
      aeruginosa. The regulatory mechanisms of alphaENaC mRNA expression by Chx and
      lipopolysaccharide (LPS) from P. aeruginosa were further studied in the present
      work. Both agents decreased alphaENaC mRNA expression to 50% of control values
      after 4 h. Chx repressed alphaENaC expression in a dose-dependent manner
      independently of protein synthesis. Although extracellular signal-regulated
      kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways
      were activated by the two treatments, their mechanisms of ENaC mRNA modulation
      were different. First, activation of the signaling pathways was sustained by Chx
      but only transiently by LPS. Second, ERK1/2 or p38 MAPK inhibition attenuated the
      effects of Chx on alphaENaC mRNA, whereas suppression of both signaling pathways
      was necessary to alleviate the outcome of LPS on alphaENaC mRNA. The molecular
      mechanisms involved in the decrease of alphaENaC expression were investigated in
      both conditions. LPS, but not Chx, significantly reduced alphaENaC promoter
      activity via the ERK1/2 and p38 MAPK pathways. These results suggest that LPS
      attenuates alphaENaC mRNA expression via diminution of transcription, whereas Chx
      could trigger some posttranscriptional mechanisms. Although LPS and Chx
      downregulate alphaENaC mRNA expression similarly and with similar signaling
      pathways, the mechanisms modulating ENaC expression are different depending on
      the nature of the cellular stress.

PMID- 24039255
TI  - Pulmonary veins in the normal lung and pulmonary hypertension due to left heart
      disease.
AB  - Despite the importance of pulmonary veins in normal lung physiology and the
      pathobiology of pulmonary hypertension with left heart disease (PH-LHD),
      pulmonary veins remain largely understudied. Difficult to identify
      histologically, lung venous endothelium or smooth muscle cells display no unique
      characteristic functional and structural markers that distinguish them from
      pulmonary arteries. To address these challenges, we undertook a search for unique
      molecular markers in pulmonary veins. In addition, we addressed the expression
      pattern of a candidate molecular marker and analyzed the structural pattern of
      vascular remodeling of pulmonary veins in a rodent model of PH-LHD and in lung
      tissue of patients with PH-LHD obtained at time of placement on a left
      ventricular assist device. We detected urokinase plasminogen activator receptor
      (uPAR) expression preferentially in normal pulmonary veins of mice, rats, and
      human lungs. Expression of uPAR remained elevated in pulmonary veins of rats with
      PH-LHD; however, we also detected induction of uPAR expression in remodeled
      pulmonary arteries. These findings were validated in lungs of patients with PH
      LHD. In selected patients with sequential lung biopsy at the time of removal of
      the left ventricular assist device, we present early data suggesting improvement
      in pulmonary hemodynamics and venous remodeling, indicating potential regression
      of venous remodeling in response to assist device treatment. Our data indicate
      that remodeling of pulmonary veins is an integral part of PH-LHD and that
      pulmonary veins share some key features present in remodeled yet not normotensive
      pulmonary arteries.

PMID- 24039257
TI  - Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction.
AB  - In this review we summarize recent major advances in our understanding on the
      molecular mechanisms, mediators, and biomarkers of acute lung injury (ALI) and
      alveolar-capillary barrier dysfunction, highlighting the role of immune cells,
      inflammatory and noninflammatory signaling events, mechanical noxae, and the
      affected cellular and molecular entities and functions. Furthermore, we address
      novel aspects of resolution and repair of ALI, as well as putative candidates for
      treatment of ALI, including pharmacological and cellular therapeutic means.

PMID- 24039258
TI  - High-altitude ophthalmic changes: an often overlooked entity.

PMID- 24039260
TI  - VhuD facilitates electron flow from H2 or formate to heterodisulfide reductase in
      Methanococcus maripaludis.
AB  - Flavin-based electron bifurcation has recently been characterized as an essential
      energy conservation mechanism that is utilized by hydrogenotrophic methanogenic
      Archaea to generate low-potential electrons in an ATP-independent manner.
      Electron bifurcation likely takes place at the flavin associated with the alpha
      subunit of heterodisulfide reductase (HdrA). In Methanococcus maripaludis the
      electrons for this reaction come from either formate or H2 via formate
      dehydrogenase (Fdh) or Hdr-associated hydrogenase (Vhu). However, how these
      enzymes bind to HdrA to deliver electrons is unknown. Here, we present evidence
      that the delta subunit of hydrogenase (VhuD) is central to the interaction of
      both enzymes with HdrA. When M. maripaludis is grown under conditions where both
      Fdh and Vhu are expressed, these enzymes compete for binding to VhuD, which in
      turn binds to HdrA. Under these conditions, both enzymes are fully functional and
      are bound to VhuD in substoichiometric quantities. We also show that Fdh
      copurifies specifically with VhuD in the absence of other hydrogenase subunits.
      Surprisingly, in the absence of Vhu, growth on hydrogen still occurs; we show
      that this involves F420-reducing hydrogenase. The data presented here represent
      an initial characterization of specific protein interactions centered on Hdr in a
      hydrogenotrophic methanogen that utilizes multiple electron donors for growth. 

PMID- 24039261
TI  - Streptomyces coelicolor polynucleotide phosphorylase can polymerize nucleoside
      diphosphates under phosphorolysis conditions, with implications for the
      degradation of structured RNAs.
AB  - We have examined the ability of wild-type polynucleotide phosphorylase (PNPase)
      from Streptomyces coelicolor and two mutant forms of the enzyme, N459D and C468A,
      to function in the polymerization of ADP and in the phosphorolysis of RNA
      substrates derived from the S. coelicolor rpsO-pnp operon. The wild-type enzyme
      was twice as active in polymerization as N459D and four times as active as C468A.
      The kcat/Km value for phosphorolysis of a structured RNA substrate by N459D was
      essentially the same as that observed for the wild-type enzyme, while C468A was
      50% as active with this substrate. A mixture of all four common nucleoside
      diphosphates increased the kcat/Km for phosphorolysis of the structured substrate
      by the wild-type enzyme by a factor of 1.7 but did not affect phosphorolysis
      catalyzed by N459D or C468A. We conducted phosphorolysis of the structured
      substrate in the presence of nucleoside diphosphates and labeled the 3' ends of
      the products of those reactions using [(32)P]pCp. Digestion of the end-labeled
      RNAs and display of the products on a sequencing gel revealed that wild-type S.
      coelicolor PNPase was able to synthesize RNA 3' tails under phosphorolysis
      conditions while the N459D and C468A mutants could not. The wild-type enzyme did
      not add 3' tails to a substrate that already possessed an unstructured 3' tail.
      We propose a model in which the transient synthesis of 3' tails facilitates the
      phosphorolysis of structured substrates by Streptomyces PNPase. 

PMID- 24039262
TI  - Control of RNA stability by NrrF, an iron-regulated small RNA in Neisseria
      gonorrhoeae.
AB  - Regulation of gene expression by small noncoding RNAs (sRNAs) plays a critical
      role in bacterial response to physiological stresses. NrrF, a trans-acting sRNA
      in Neisseria meningitidis and Neisseria gonorrhoeae, has been shown in the
      meningococcus to control indirectly, in response to iron (Fe) availability, the
      transcription of genes encoding subunits of succinate dehydrogenase, a Fe
      requiring enzyme. Given that in other organisms, sRNAs target multiple mRNAs to
      control gene expression, we used a global approach to examine the role of NrrF in
      controlling gonococcal transcription. Three strains, including N. gonorrhoeae
      FA1090, an nrrF deletion mutant, and a complemented derivative, were examined
      using a custom CombiMatrix microarray to assess the role of this sRNA in
      controlling gene expression in response to Fe availability. In the absence of
      NrrF, the mRNA half-lives for 12 genes under Fe-depleted growth conditions were
      longer than those in FA1090. The 12 genes controlled by NrrF encoded proteins
      with biological functions including energy metabolism, oxidative stress,
      antibiotic resistance, and amino acid synthesis, as well as hypothetical proteins
      and a regulatory protein whose functions are not fully understood. 

PMID- 24039263
TI  - Diversity of cobalamin riboswitches in the corrinoid-producing organohalide
      respirer Desulfitobacterium hafniense.
AB  - The strategic adaptation of prokaryotes in polluted niches involves the efficient
      regulation of their metabolism. The obligate anaerobe and metabolically versatile
      Desulfitobacterium hafniense reductively dechlorinates halogenated organic
      compounds (so-called organohalides). Some D. hafniense strains carry out
      organohalide respiration (OHR), a process which requires the use of corrinoid as
      a cofactor in reductive dehalogenases, the key enzymes in OHR. We report here the
      diversity of the cobalamin riboswitches that possibly regulate the corrinoid
      metabolism for D. hafniense. The analysis of available D. hafniense genomes
      indicates the presence of 18 cobalamin riboswitches located upstream of genes
      whose products are mainly involved in corrinoid biosynthesis and transport. To
      obtain insight into their function, the secondary structures of three of these
      RNA elements were predicted by Mfold, as well as analyzed by in-line probing.
      These RNA elements both display diversity in their structural elements and
      exhibit various affinities toward adenosylcobalamin that possibly relates to
      their role in the regulation of corrinoid metabolism. Furthermore,
      adenosylcobalamin-induced in vivo repression of RNA synthesis of the downstream
      located genes indicates that the corrinoid transporters and biosynthetic enzymes
      in D. hafniense strain TCE1 are regulated at the transcriptional level. Taken
      together, the riboswitch-mediated regulation of the complex corrinoid metabolism
      in D. hafniense could be of crucial significance in environments polluted with
      organohalides both to monitor their intracellular corrinoid level and to coexist
      with corrinoid-auxotroph OHR bacteria. 

PMID- 24039265
TI  - Identification, purification, and characterization of a novel amino acid
      racemase, isoleucine 2-epimerase, from Lactobacillus species.
AB  - Accumulation of d-leucine, d-allo-isoleucine, and d-valine was observed in the
      growth medium of a lactic acid bacterium, Lactobacillus otakiensis JCM 15040, and
      the racemase responsible was purified from the cells and identified. The N
      terminal amino acid sequence of the purified enzyme was GKLDKASKLI, which is
      consistent with that of a putative gamma-aminobutyrate aminotransferase from
      Lactobacillus buchneri. The putative gamma-aminobutyrate aminotransferase gene
      from L. buchneri JCM 1115 was expressed in recombinant Escherichia coli and then
      purified to homogeneity. The enzyme catalyzed the racemization of a broad
      spectrum of nonpolar amino acids. In particular, it catalyzed at high rates the
      epimerization of l-isoleucine to d-allo-isoleucine and d-allo-isoleucine to l
      isoleucine. In contrast, the enzyme showed no gamma-aminobutyrate
      aminotransferase activity. The relative molecular masses of the subunit and
      native enzyme were estimated to be about 49 kDa and 200 kDa, respectively,
      indicating that the enzyme was composed of four subunits of equal molecular
      masses. The Km and Vmax values of the enzyme for l-isoleucine were 5.00 mM and
      153 MUmol.min(-1).mg(-1), respectively, and those for d-allo-isoleucine were 13.2
      mM and 286 MUmol.min(-1).mg(-1), respectively. Hydroxylamine and other inhibitors
      of pyridoxal 5'-phosphate-dependent enzymes completely blocked the enzyme
      activity, indicating the enzyme requires pyridoxal 5'-phosphate as a coenzyme.
      This is the first evidence of an amino acid racemase that specifically catalyzes
      racemization of nonpolar amino acids at the C-2 position. 

PMID- 24039264
TI  - The second messenger cyclic Di-GMP regulates Clostridium difficile toxin
      production by controlling expression of sigD.
AB  - The Gram-positive obligate anaerobe Clostridium difficile causes potentially
      fatal intestinal diseases. How this organism regulates virulence gene expression
      is poorly understood. In many bacterial species, the second messenger cyclic di
      GMP (c-di-GMP) negatively regulates flagellar motility and, in some cases,
      virulence. c-di-GMP was previously shown to repress motility of C. difficile.
      Recent evidence indicates that flagellar gene expression is tightly linked with
      expression of the genes encoding the two C. difficile toxins TcdA and TcdB, which
      are key virulence factors for this pathogen. Here, the effect of c-di-GMP on
      expression of the toxin genes tcdA and tcdB was determined, and the mechanism
      connecting flagellar and toxin gene expressions was examined. In C. difficile,
      increasing c-di-GMP levels reduced the expression levels of tcdA and tcdB, as
      well as that of tcdR, which encodes an alternative sigma factor that activates
      tcdA and tcdB expression. We hypothesized that the C. difficile orthologue of the
      flagellar alternative sigma factor SigD (FliA; sigma(28)) mediates regulation of
      toxin gene expression in response to c-di-GMP. Indeed, ectopic expression of sigD
      in C. difficile resulted in increased expression levels of tcdR, tcdA, and tcdB.
      Furthermore, sigD expression enhanced toxin production and increased the
      cytopathic effect of C. difficile on cultured fibroblasts. Finally, evidence is
      provided that SigD directly activates tcdR expression and that SigD cannot
      activate tcdA or tcdB expression independent of TcdR. Taken together, these data
      suggest that SigD positively regulates toxin genes in C. difficile and that c-di
      GMP can inhibit both motility and toxin production via SigD, making this
      signaling molecule a key virulence gene regulator in C. difficile. 

PMID- 24039266
TI  - The Sulfolobus initiator element is an important contributor to promoter
      strength.
AB  - Basal elements in archaeal promoters, except for putative initiator elements
      encompassing transcription start sites, are well characterized. Here, we employed
      the Sulfolobus araS promoter as a model to study the function of the initiator
      element (Inr) in archaea. We have provided evidence for the presence of a third
      core promoter element, the Sulfolobus Inr, whose action depends on a TATA box and
      the TFB recognition element (BRE). Substitution mutations in the araS Inr did not
      alter the location of the transcription start site. Using systematic mutagenesis,
      the most functional araS Inr was defined as +1 GAGAMK +6 (where M is A/C and K is
      G/T). Furthermore, WebLogo analysis of a subset of promoters with coding
      sequences for 5' untranslated regions (UTRs) larger than 4 nucleotides (nt) in
      Sulfolobus solfataricus P2 identified an Inr consensus that exactly matches the
      functional araS Inr sequence. Moreover, mutagenesis of 3 randomly selected
      promoters confirmed the Inr sequences to be important for basal promoter strength
      in the subgroup. Importantly, the result of the araS Inr being added to the Inr
      less promoters indicates that the araS Inr, the core promoter element, is able to
      enhance the strength of Inr-less promoters. We infer that transcription factor B
      (TFB) and subunits of RNA polymerase bind the Inr to enhance promoter strength.
      Taken together, our data suggest that the presence or absence of an Inr on basal
      promoters is important for global gene regulation in Sulfolobus. 

PMID- 24039267
TI  - MecA protein acts as a negative regulator of genetic competence in Streptococcus
      mutans.
AB  - Streptococcus mutans develops competence for genetic transformation through a
      complex network that receives inputs from at least two signaling peptides,
      competence-stimulating peptide (CSP) and sigX-inducing peptide (XIP). The key
      step of competence induction is the transcriptional activation of comX, which
      encodes an alternative sigma factor, SigX (sigma(X)), controlling the expression
      of late competence genes essential for DNA uptake and recombination. In this
      study, we provide evidence that MecA acts as a negative regulator in the
      posttranslational regulation of SigX in S. mutans. Using luxAB transcriptional
      reporter strains, we demonstrate that MecA represses the expression of late
      competence genes in S. mutans grown in a complex medium that is subpermissive for
      competence induction by CSP. The negative regulation of competence by MecA
      requires the presence of a functional SigX. Accordingly, inactivation of MecA
      results in a prolonged competence state of S. mutans under this condition. We
      have also found that the AAA+ protease ClpC displays a similar repressing effect
      on late competence genes, suggesting that both MecA and ClpC function
      coordinately to regulate competence in the same regulatory circuit in S. mutans.
      This suggestion is strongly supported by the results of bacterial two-hybrid
      assays, which demonstrate that MecA interacts with both SigX and ClpC, forming a
      ternary SigX-MecA-ClpC complex. Western blot analysis also confirms that
      inactivation of MecA or ClpC results in the intracellular accumulation of the
      SigX in S. mutans. Together, our data support the notion that MecA mediates the
      formation of a ternary SigX-MecA-ClpC complex that sequesters SigX and thereby
      negatively regulates genetic competence in S. mutans. 

PMID- 24039268
TI  - Identifying bacterial menu choices from the host buffet during infections.

PMID- 24039269
TI  - Expanding the cyanuric acid hydrolase protein family to the fungal kingdom.
AB  - The known enzymes that open the s-triazine ring, the cyanuric acid hydrolases,
      have been confined almost exclusively to the kingdom Bacteria and are all
      homologous members of the rare cyanuric acid hydrolase/barbiturase protein
      family. In the present study, a filamentous fungus, Sarocladium sp. strain CA,
      was isolated from soil by enrichment culturing using cyanuric acid as the sole
      source of nitrogen. A reverse-genetic approach identified a fungal cyanuric acid
      hydrolase gene composed of two exons and one intron. The translated spliced
      sequence was 39 to 53% identical to previously characterized bacterial cyanuric
      acid hydrolases. The sequence was used to generate a gene optimized for
      expression in Escherichia coli and encoding an N-terminally histidine-tagged
      protein. The protein was purified by nickel affinity and anion-exchange
      chromatography. The purified protein was shown by (13)C nuclear magnetic
      resonance ((13)C-NMR) to produce carboxybiuret as the product, which
      spontaneously decarboxylated to yield biuret and carbon dioxide. The protein was
      very narrow in substrate specificity, showing activity only with cyanuric acid
      and N-methyl cyanuric acid. Barbituric acid was an inhibitor of enzyme activity.
      Sequence analysis identified genes with introns in other fungi from the
      Ascomycota that, if spliced, are predicted to encode proteins with cyanuric acid
      hydrolase activity. The Ascomycota cyanuric acid hydrolase homologs are most
      closely related to cyanuric acid hydrolases from Actinobacteria. 

PMID- 24039270
TI  - Correction.

PMID- 24039271
TI  - Does Specialization Explain Marriage Penalties and Premiums?
AB  - Married men's wage premium is often attributed to within-household
      specialization: men can devote more effort to wage-earning when their wives
      assume responsibility for household labor. We provide a comprehensive evaluation
      of the specialization hypothesis, arguing that, if specialization causes the male
      marriage premium, married women should experience wage losses. Furthermore,
      specialization by married parents should augment the motherhood penalty and the
      fatherhood premium for married as compared to unmarried parents. Using fixed
      effects models and data from the NLSY79, we estimate within-gender differences in
      wages according to marital status and between-gender differences in the
      associations between marital status and wages. We then test whether
      specialization on time use, job traits, and tenure accounts for the observed
      associations. Results for women do not support the specialization hypothesis.
      Childless men and women both receive a marriage premium. Marriage augments the
      fatherhood premium but not the motherhood penalty. Changes in own and spousal
      employment hours, job traits, and tenure appear to benefit both married men and
      women, although men benefit more. Marriage changes men's labor market behavior in
      ways that augment wages, but these changes do not appear to occur at the expense
      of women's wages.

PMID- 24039272
TI  - Computing Confidence Bounds for Power and Sample Size of the General Linear
      Univariate Model.
AB  - The power of a test, the probability of rejecting the null hypothesis in favor of
      an alternative, may be computed using estimates of one or more distributional
      parameters. Statisticians frequently fix mean values and calculate power or
      sample size using a variance estimate from an existing study. Hence computed
      power becomes a random variable for a fixed sample size. Likewise, the sample
      size necessary to achieve a fixed power varies randomly. Standard statistical
      practice requires reporting uncertainty associated with such point estimates.
      Previous authors studied an asymptotically unbiased method of obtaining
      confidence intervals for noncentrality and power of the general linear univariate
      model in this setting. We provide exact confidence intervals for noncentrality,
      power, and sample size. Such confidence intervals, particularly one-sided
      intervals, help in planning a future study and in evaluating existing studies.

PMID- 24039273
TI  - Estimation of Progression-Free Survival for All Treated Patients in the
      Randomized Discontinuation Trial Design.
AB  - The randomized discontinuation trial (RDT) design is an enrichment-type design
      that has been used in a variety of diseases to evaluate the efficacy of new
      treatments. The RDT design seeks to select a more homogeneous group of patients,
      consisting of those who are more likely to show a treatment benefit if one
      exists. In oncology, the RDT design has been applied to evaluate the effects of
      cytostatic agents, that is, drugs that act primarily by slowing tumor growth
      rather than shrinking tumors. In the RDT design, all patients receive treatment
      during an initial, open-label run-in period of duration T. Patients with
      objective response (substantial tumor shrinkage) remain on therapy while those
      with early progressive disease are removed from the trial. Patients with stable
      disease (SD) are then randomized to either continue active treatment or switched
      to placebo. The main analysis compares outcomes, for example, progression-free
      survival (PFS), between the two randomized arms. As a secondary objective,
      investigators may seek to estimate PFS for all treated patients, measured from
      the time of entry into the study, by combining information from the run-in and
      post run-in periods. For t <= T, PFS is estimated by the observed proportion of
      patients who are progression-free among all patients enrolled. For t > T, the
      estimate can be expressed as S(t) = pOR * SOR(t - T) + pSD * SSD(t - T), where
      pOR is the estimated probability of response during the run-in period, pSD is the
      estimated probability of SD, and SOR(t - T) and SSD(t - T) are the Kaplan-Meier
      estimates of subsequent PFS in the responders and patients with SD randomized to
      continue treatment, respectively. In this article, we derive the variance of
      S(t), enabling the construction of confidence intervals for both S(t) and the
      median survival time. Simulation results indicate that the method provides
      accurate coverage rates. An interesting aspect of the design is that outcomes
      during the run-in phase have a negative multinomial distribution, something not
      frequently encountered in practice.

PMID- 24039274
TI  - Inversion of left-right asymmetry alters performance of Xenopus tadpoles in
      nonlateralized cognitive tasks.
AB  - Left-right behavioural biases are well documented across the animal kingdom, and
      handedness has long been associated with cognitive performance. However, the
      relationship between body laterality and cognitive ability is poorly understood.
      The embryonic pathways dictating normal left-right patterning have been
      molecularly dissected in model vertebrates, and numerous genetic and
      pharmacological treatments now facilitate experimental randomization or reversal
      of the left-right axis in these animals. Several recent studies showed a link
      between brain asymmetry and strongly lateralized behaviours such as eye use
      preference. However, links between laterality of the body and performance on
      cognitive tasks utilizing nonlateralized cues remain unknown. Xenopus tadpoles
      are an established model for the study of early left-right patterning, and
      protocols were recently developed to quantitatively evaluate learning and memory
      in these animals. Using an automated testing and training platform, we tested
      wild-type, left-right-randomized and left-right-reversed tadpoles for their
      ability to learn colour cues in an automated assay. Our results indicate that
      animals with either randomization or reversal of somatic left-right patterning
      learned more slowly than wild-type siblings, although all groups were able to
      reach the same performance optimum given enough training sessions. These results
      are the first analysis of the link between body laterality and learning of
      nonlateralized cues, and they position the Xenopus tadpole as an attractive and
      tractable model for future studies of the links between asymmetry of the body,
      lateralization of the brain and behaviour.

PMID- 24039276
TI  - Possibilities and limitations of the ART-Sample algorithm for reconstruction of
      3D temperature fields and the influence of opaque obstacles.
AB  - The need for the measurement of complex, unsteady, three-dimensional (3D)
      temperature distributions arises in a variety of engineering applications, and
      tomographic techniques are applied to accomplish this goal. Holographic
      interferometry (HI), one of the optical methods used for visualizing temperature
      fields, combined with tomographic reconstruction techniques requires multi
      directional interferometric data to recover the 3D information. However, the
      presence of opaque obstacles (such as solid objects in the flow field and
      heaters) in the measurement volume, prevents the probing light beams from
      traversing the entire measurement volume. As a consequence, information on the
      average value of the field variable will be lost in regions located in the shade
      of the obstacle. The capability of the ART-Sample tomographic reconstruction
      method to recover 3D temperature distributions both in unobstructed temperature
      fields and in the presence of opaque obstacles is discussed in this paper. A
      computer code for tomographic reconstruction of 3D temperature fields from 2D
      projections was developed. In the paper, the reconstruction accuracy is discussed
      quantitatively both without and with obstacles in the measurement volume for a
      set of phantom functions mimicking realistic temperature distributions. The
      reconstruction performance is optimized while minimizing the number of
      irradiation directions (experimental hardware requirements) and computational
      effort. For the smooth temperature field both with and without obstacles, the
      reconstructions produced by this algorithm are good, both visually and using
      quantitative criteria. The results suggest that the location and the size of the
      obstacle and the number of viewing directions will affect the reconstruction of
      the temperature field. When the best performance parameters of the ART-Sample
      algorithm identified in this paper are used to reconstruct the 3D temperature
      field, the 3D reconstructions with and without obstacle are both excellent, and
      the obstacle has little influence on the reconstruction. The results indicate
      that the ART-Sample algorithm can successfully recover instantaneous 3D
      temperature distributions in the presence of opaque obstacles with only 4 viewing
      directions.

PMID- 24039275
TI  - Collagen-like peptides and peptide-polymer conjugates in the design of assembled
      materials.
AB  - Collagen is the most abundant protein in mammals, and there has been long
      standing interest in understanding and controlling collagen assembly in the
      design of new materials. Collagen-like peptides (CLP), also known as collagen
      mimetic peptides (CMP) or collagen-related peptides (CRP), have thus been widely
      used to elucidate collagen triple helix structure as well as to produce higher
      order structures that mimic natural collagen fibers. This mini-review provides an
      overview of recent progress on these topics, in three broad topical areas. The
      first focuses on reported developments in deciphering the chemical basis for
      collagen triple helix stabilization, which we review not with the intent of
      describing the basic structure and biological function of collagen, but to
      summarize different pathways for designing collagen-like peptides with high
      thermostability. Various approaches for producing higher-order structures via CLP
      self-assembly, via various types of intermolecular interaction, are then
      discussed. Finally, recent developments in a new area, the production of polymer
      CLP bioconjugates, are summarized. Biological applications of collagen contained
      hydrogels are also included in this section. The topics may serve as a guide for
      the design of collagen-like peptides and their bioconjugates for targeted
      application in the biomedical arena.

PMID- 24039277
TI  - Behavioral Signal Processing: Deriving Human Behavioral Informatics From Speech
      and Language: Computational techniques are presented to analyze and model
      expressed and perceived human behavior-variedly characterized as typical,
      atypical, distressed, and disordered-from speech and language cues and their
      applications in health, commerce, education, and beyond.
AB  - The expression and experience of human behavior are complex and multimodal and
      characterized by individual and contextual heterogeneity and variability. Speech
      and spoken language communication cues offer an important means for measuring and
      modeling human behavior. Observational research and practice across a variety of
      domains from commerce to healthcare rely on speech- and language-based
      informatics for crucial assessment and diagnostic information and for planning
      and tracking response to an intervention. In this paper, we describe some of the
      opportunities as well as emerging methodologies and applications of human
      behavioral signal processing (BSP) technology and algorithms for quantitatively
      understanding and modeling typical, atypical, and distressed human behavior with
      a specific focus on speech- and language-based communicative, affective, and
      social behavior. We describe the three important BSP components of acquiring
      behavioral data in an ecologically valid manner across laboratory to real-world
      settings, extracting and analyzing behavioral cues from measured data, and
      developing models offering predictive and decision-making support. We highlight
      both the foundational speech and language processing building blocks as well as
      the novel processing and modeling opportunities. Using examples drawn from
      specific real-world applications ranging from literacy assessment and autism
      diagnostics to psychotherapy for addiction and marital well being, we illustrate
      behavioral informatics applications of these signal processing techniques that
      contribute to quantifying higher level, often subjectively described, human
      behavior in a domain-sensitive fashion.

PMID- 24039278
TI  - DRUG RISK: A CROSS-SECTIONAL EXPLORATION OF THE INFLUENCE OF FAMILY-OF-ORIGIN AND
      CURRENT SITUATIONAL CIRCUMSTANCES.
AB  - The main objective of this paper is to investigate potential predictors of drug
      risk among a community-based sample of individuals who are exposed to illicit
      drugs. The four domains of interest are individual socio-demographic and social
      psychological attributes, current situational circumstances and family-of-origin
      characteristics. Interviews were conducted with 242 individuals who were
      recruited in Atlanta, Georgia. Initial descriptive analyses were followed by
      multivariate analyses. The final model predicted 60% of the variance in drug
      risk. Current situational circumstances were statistically significant regarding
      drug risk. Family-of-origin characteristics also were significant, even when
      entered into the predictive model after current situational circumstances. In
      addition to individual social-psychological characteristics such as depression
      and self-esteem, the impact of childhood emotional abuse is noted. The findings
      indicate a need for considering proximal as well as more distal influences on
      drug risk behavior when designing drug use prevention and intervention programs.

PMID- 24039279
TI  - A Qualitative Study of Barriers to the Utilization of HIV Testing Services Among
      Rural African American Cocaine Users.
AB  - This qualitative study is about barriers to the utilization of HIV testing as
      perceived by African Americans who have recently used cocaine and who live in the
      rural Delta region of Arkansas. Affordability, physical accessibility, and
      geographic availability were not perceived as barriers to HIV testing in this
      sample, yet acceptability was still perceived as poor. Acceptability due to
      social mores and norms was a major barrier. Many said testing was unacceptable
      because of fear of social costs. Many were confident of being HIV-negative based
      on risky assumptions about testing and the notification process. Small-town
      social and sexual networks added to concerns about reputation and risk. System
      approaches may fail if they focus solely on improving access to HIV services but
      do not take into consideration deeply internalized experiences of rural African
      Americans as well as involvement of the community in developing programs and
      services.

PMID- 24039280
TI  - The Longitudinal Relation Between Academic/Cognitive Skills and Externalizing
      Behavior Problems in Preschool Children.
AB  - OBJECTIVE: Existing research suggests that there is a relation between
      academic/cognitive deficits and externalizing behavior in young children, but the
      direction of this relation is unclear. The present study tested competing models
      of the relation between academic/cognitive functioning and behavior problems
      during early childhood. METHOD: Participants were 221 children (120 boys, 101
      girls) who participated in a longitudinal study from age 3 to 6. RESULTS: A
      reciprocal relation (Model 3) was observed only between inattention and academic
      achievement; this relation remained controlling for SES and family stress. The
      relation between inattention and cognitive ability was consistent with Model 1
      (cognitive skills predicting later inattention) with controls. For hyperactivity
      and aggression, there was some support for Model 2 (early behavior predicting
      later academic/cognitive ability), but this model was no longer supported when
      controlling for family functioning. CONCLUSION: These results suggest that the
      relation between academic achievement/cognitive ability and externalizing
      problems may be driven primarily by inattention. These results also suggest that
      this relation is evident early in development, highlighting the need for early
      assessment and intervention.

PMID- 24039281
TI  - Clinical features and treatment of ocular toxoplasmosis.
AB  - Ocular toxoplasmosis is a disease caused by the infection with Toxoplasma gondii
      through congenital or acquired routes. Once the parasite reaches the retina, it
      proliferates within host cells followed by rupture of the host cells and invasion
      into neighboring cells to make primary lesions. Sometimes the restricted parasite
      by the host immunity in the first scar is activated to infect another lesion
      nearby the scar. Blurred vision is the main complaint of ocular toxoplasmic
      patients and can be diagnosed by detection of antibodies or parasite DNA. Ocular
      toxoplasmosis needs therapy with several combinations of drugs to eliminate the
      parasite and accompanying inflammation; if not treated it sometimes leads to loss
      of vision. We describe here clinical features and currently available
      chemotherapy of ocular toxoplasmosis. 

PMID- 24039282
TI  - Genetic characterization of clinical acanthamoeba isolates from Japan using
      nuclear and mitochondrial small subunit ribosomal RNA.
AB  - Because of an increased number of Acanthamoeba keratitis (AK) along with
      associated disease burdens, medical professionals have become more aware of this
      pathogen in recent years. In this study, by analyzing both the nuclear 18S small
      subunit ribosomal RNA (18S rRNA) and mitochondrial 16S rRNA gene loci, 27
      clinical Acanthamoeba strains that caused AK in Japan were classified into 3
      genotypes, T3 (3 strains), T4 (23 strains), and T5 (one strain). Most haplotypes
      were identical to the reference haplotypes reported from all over the world, and
      thus no specificity of the haplotype distribution in Japan was found. The T4 sub
      genotype analysis using the 16S rRNA gene locus also revealed a clear sub
      conformation within the T4 cluster, and lead to the recognition of a new sub
      genotype T4i, in addition to the previously reported sub-genotypes T4a-T4h.
      Furthermore, 9 out of 23 strains in the T4 genotype were identified to a specific
      haplotype (AF479533), which seems to be a causal haplotype of AK. While
      heterozygous nuclear haplotypes were observed from 2 strains, the mitochondrial
      haplotypes were homozygous as T4 genotype in the both strains, and suggested a
      possibility of nuclear hybridization (mating reproduction) between different
      strains in Acanthamoeba. The nuclear 18S rRNA gene and mitochondrial 16S rRNA
      gene loci of Acanthamoeba spp. possess different unique characteristics usable
      for the genotyping analyses, and those specific features could contribute to the
      establishment of molecular taxonomy for the species complex of Acanthamoeba. 

PMID- 24039283
TI  - Overexpression of ubiquitin and amino acid permease genes in association with
      antimony resistance in Leishmania tropica field isolates.
AB  - The mainstay therapy against leishmaniasis is still pentavalent antimonial drugs;
      however, the rate of antimony resistance is increasing in endemic regions such as
      Iran. Understanding the molecular basis of resistance to antimonials could be
      helpful to improve treatment strategies. This study aimed to recognize genes
      involved in antimony resistance of Leishmania tropica field isolates. Sensitive
      and resistant L. tropica parasites were isolated from anthroponotic cutaneous
      leishmaniasis patients and drug susceptibility of parasites to meglumine
      antimoniate (Glucantime(r)) was confirmed using in vitro assay. Then,
      complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real
      time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from
      resistant and sensitive L. tropica isolates. We identified 2 known genes,
      ubiquitin implicated in protein degradation and amino acid permease (AAP3)
      involved in arginine uptake. Also, we identified 1 gene encoding hypothetical
      protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54
      fold), and AAP3 (2.86-fold) (P<0.05) in a resistant isolate compared to a
      sensitive one. Our results suggest that overexpression of ubiquitin and AAP3
      could potentially implicated in natural antimony resistance. 

PMID- 24039284
TI  - Influence of Toxoplasma gondii acute infection on cholinesterase activities of
      Wistar rats.
AB  - Several studies have shown the mechanisms and importance of immune responses
      against Toxoplasma gondii infection and the notable role of cholinesterases in
      inflammatory reactions. However, the association between those factors has not
      yet been investigated. Therefore, the aim of this study was to evaluate the
      acetylcholinesterase (AChE) activity in blood and lymphocytes and the activity of
      butyrylcholinesterase (BChE) in serum of rats experimentally infected with T.
      gondii during the acute phase of infection. For that, an in vivo study was
      performed with evaluations of AChE and BChE activities on days 5 and 10 post
      infection (PI). The activity of AChE in blood was increased on day 5 PI, while in
      lymphocytes its activity was enhanced on days 5 and 10 PI (P<0.05). No
      significant difference was observed between groups regarding to the activity of
      BChE in serum. A positive (P<0.01) correlation was observed between AChE activity
      and number of lymphocytes. The role of AChE as an inflammatory marker is well
      known in different pathologies; thus, our results lead to the hypothesis that
      AChE has an important role in modulation of early immune responses against T.
      gondii infection. 

PMID- 24039285
TI  - Balantidium honghuensis n. sp. (Ciliophora: Trichostomatidae) from the rectum of
      Rana nigromaculata and R. limnocharis from Honghu Lake, China.
AB  - A new trichostome ciliate, Balantidium honghuensis n. sp., was isolated from the
      recta of Rana nigromaculata and R. limnocharis during parasite surveys in Honghu
      Lake, Hubei Province, central China in summer of 2010 and 2011. Its detailed
      morphometric characters based on LM and SEM studies were described herein. The
      organism is oval in shape and thickly ciliated. The vestibulum is "V" shaped and
      occupies about 1/3 to 2/5 of the body length. The vestibular and nearby regions
      possess strong peripheral fibers which form a marked axial fiber about the
      cytopharynx. More than 10 contractile vacuoles are distributed along the
      periphery of the latter body. Comparisions were made between this new species and
      B. sinensis Nie, 1935. They were discriminated from each other in terms of
      general body forms, body size, and vestibulum shapes. Besides, special attention
      was paid to its high-speed daughter swarmers which we believed to be the
      infective stage of B. honghuensis. Possible infection routes of anura amphibian
      balantidia were discussed. 

PMID- 24039286
TI  - Serodiagnosis of toxocariasis by ELISA using crude antigen of Toxocara canis
      larvae.
AB  - Toxocariasis is a worldwide zoonosis caused by larvae of ascarid nematodes of
      dogs or cats, Toxocara canis or T. cati. Diagnosis of human toxocariasis
      currently relies on serology that uses T. canis excretory-secretory antigen to
      detect specific IgG antibodies by ELISA. We investigated the serodiagnostic
      efficacy of ELISA using crude antigen of T. canis larvae (TCLA). Serum specimens
      of 64 clinically confirmed toxocariasis, 115 healthy controls, and 119 other
      tissue-invading helminthiases were screened by ELISA using TCLA. The ELISA using
      TCLA showed 92.2% (59/64 patient samples) sensitivity and 86.6% (103/119)
      specificity. Its positive diagnostic predictivity was 78.7% and negative
      predictivity was 97.8%. No serum of healthy controls reacted but that of
      anisakiasis (45.5%), gnathostomiasis (19.2%), clonorchiasis (15.8%), sparganosis
      (11.1%), and cysticercosis (6.3%) cross-reacted. Immunoblot analysis on TCLA
      recognized antigenic proteins of 28- and 30-kDa bands in their dominant protein
      quantity and strong blotting reactivity. The present results indicate that the
      ELISA using our TCLA antigen is acceptable by the sensitivity and specificity for
      serodiagnosis of human toxocariasis. ELISA with TCLA is recommended to make
      differential diagnosis for patients with any sign of organ infiltration and
      eosinophilia. 

PMID- 24039287
TI  - First record of Bourgelatia diducta (Nematoda: Chabertiidae) from wild boars in
      the Republic of Korea.
AB  - This study describes the first record of Bourgelatia diducta (Nematoda:
      Chabertiidae) from wild boars in the Republic of Korea (=South Korea).
      Gastrointestinal tracts of 87 Korean wild boars (Sus scrofa coreanus) hunted in
      mountains in the south-western part of South Korea between 2009 and 2012 were
      examined for their visceral helminths. B. diducta, as identified by morphological
      characteristics of the head and tail, were recovered from the large intestine of
      47 (54%) wild boars. The average length of adult female worms was 11.3+/-0.87 mm
      and the thickest part of the body measured 0.54+/-0.04 mm in maximum width, while
      those of males were 9.8+/-0.72 and 0.45+/-0.03 mm, respectively. The
      characteristic J-shaped type II ovejector was observed in females, and the type
      II dorsal ray with 2 rami on each side of the median fissure was uniquely seen in
      males. The buccal capsule was small, relatively thin-walled, cylindrical, very
      short, and ring-shaped. The externodorsal ray arose from a common stem with the
      dorsal ray. The cervical groove was absent. The anterior extremity was equipped
      with 20-22 external corona radiata, 4 cephalic papillae and 2 lateral amphids
      around the mouth. The eggs were 66.0*38.9 um in average size. By the present
      study, B. diducta (Nematoda: Chabertiidae) is recorded for the first time in
      South Korea. Additionally, morphological characteristics and identification keys
      provided in the present study will be helpful in the faunistic or taxonomic
      studies for strongylid nematodes related. 

PMID- 24039288
TI  - Genetic variation of Taenia pisiformis collected from Sichuan, China, based on
      the mitochondrial cytochrome B gene.
AB  - Taenia pisiformis is one of the most important parasites of canines and rabbits.
      T. pisiformis cysticercus (the larval stage) causes severe damage to rabbit
      breeding, which results in huge economic losses. In this study, the genetic
      variation of T. pisiformis was determined in Sichuan Province, China. Fragments
      of the mitochondrial cytochrome b (cytb) (922 bp) gene were amplified in 53
      isolates from 8 regions of T. pisiformis. Overall, 12 haplotypes were found in
      these 53 cytb sequences. Molecular genetic variations showed 98.4% genetic
      variation derived from intra-region. FST and Nm values suggested that 53 isolates
      were not genetically differentiated and had low levels of genetic diversity.
      Neutrality indices of the cytb sequences showed the evolution of T. pisiformis
      followed a neutral mode. Phylogenetic analysis revealed no correlation between
      phylogeny and geographic distribution. These findings indicate that 53 isolates
      of T. pisiformis keep a low genetic variation, which provide useful knowledge for
      monitoring changes in parasite populations for future control strategies. 

PMID- 24039289
TI  - Skeletal manifestations of hydatid disease in Serbia: demographic distribution,
      site involvement, radiological findings, and complications.
AB  - Although Serbia is recognized as an endemic country for echinococcosis, no
      information about precise incidence in humans has been available. The aim of this
      study was to investigate the skeletal manifestations of hydatid disease in
      Serbia. This retrospective study was conducted by reviewing the medical database
      of Institute for Pathology (Faculty of Medicine in Belgrade), a reference
      institution for bone pathology in Serbia. We reported a total of 41 patients with
      bone cystic echinococcosis (CE) during the study period. The mean age of 41
      patients was 40.9+/-18.8 years. In 39% of patients, the fracture line was the
      only visible radiological sign, followed by cyst and tumefaction. The spine was
      the most commonly involved skeletal site (55.8%), followed by the femur (18.6%),
      pelvis (13.9%), humerus (7.0%), rib (2.3%), and tibia (2.3%). Pain was the
      symptom in 41.5% of patients, while some patients demonstrated complications such
      as paraplegia (22.0%), pathologic fracture (48.8%), and scoliosis (9.8%). The
      pathological fracture most frequently affected the spine (75.0%) followed by the
      femur (20.0%) and tibia (5.0%). However, 19.5% of patients didn't develop any
      complication or symptom. In this study, we showed that bone CE is not uncommon in
      Serbian population. As reported in the literature, therapy of bone CE is
      controversial and its results are poor. In order to improve the therapy outcome,
      early diagnosis, before symptoms and complications occur, can be contributive. 

PMID- 24039290
TI  - A waterborne outbreak and detection of cryptosporidium oocysts in drinking water
      of an older high-rise apartment complex in seoul.
AB  - From May to June 2012, a waterborne outbreak of 124 cases of cryptosporidiosis
      occurred in the plumbing systems of an older high-rise apartment complex in
      Seoul, Republic of Korea. The residents of this apartment complex had symptoms of
      watery diarrhea and vomiting. Tap water samples in the apartment complex and its
      adjacent buildings were collected and tested for 57 parameters under the Korean
      Drinking Water Standards and for additional 11 microbiological parameters. The
      microbiological parameters included total colony counts, Clostridium perfringens,
      Enterococcus, fecal streptococcus, Salmonella, Shigella, Pseudomonas aeruginosa,
      Cryptosporidium oocysts, Giardia cysts, total culturable viruses, and Norovirus.
      While the tap water samples of the adjacent buildings complied with the Korean
      Drinking Water Standards for all parameters, fecal bacteria and Cryptosporidium
      oocysts were detected in the tap water samples of the outbreak apartment complex.
      It turned out that the agent of the disease was Cryptosporidium parvum. The
      drinking water was polluted with sewage from a septic tank in the apartment
      complex. To remove C. parvum oocysts, we conducted physical processes of cleaning
      the water storage tanks, flushing the indoor pipes, and replacing old pipes with
      new ones. Finally we restored the clean drinking water to the apartment complex
      after identification of no oocysts. 

PMID- 24039291
TI  - Cutaneous gnathostomiasis with recurrent migratory nodule and persistent
      eosinophilia: a case report from China.
AB  - The present study reports a human case of cutaneous gnathostomiasis with
      recurrent migratory nodule and persistent eosinophilia in China. A 52-year-old
      woman from Henan Province, central China, presented with recurrent migratory
      reddish swelling and subcutaneous nodule in the left upper arm and on the back
      for 3 months. Blood examination showed eosinophila (21.2%), and anti-sparganum
      antibodies were positive. Skin biopsy of the lesion and histopathological
      examinations revealed dermal infiltrates of eosinophils but did not show any
      parasites. Thus, the patient was first diagnosed as sparganosis; however, new
      migratory swellings occurred after treatment with praziquantel for 3 days. On
      further inquiring, she recalled having eaten undercooked eels and specific
      antibodies to the larvae of Gnathostoma spinigerum were detected. The patient was
      definitely diagnosed as cutaneous gnathostomiasis caused by Gnathostoma sp. and
      treated with albendazole (1,000 mg/day) for 15 days, and the subsequent papule
      and blister developed after the treatment. After 1 month, laboratory findings
      indicated a reduced eosinophil count (3.3%). At her final follow-up 18 months
      later, the patient had no further symptoms and anti-Gnathostoma antibodies became
      negative. Conclusively, the present study is the first report on a human case of
      cutaneous gnathostomiasis in Henan Province, China, based on the past history
      (eating undercooked eels), clinical manifestations (migratory subcutaneous nodule
      and persistent eosinophilia), and a serological finding (positive for specific
      anti-Gnathostoma antibodies). 

PMID- 24039292
TI  - A case of Diphyllobothrium nihonkaiense infection as confirmed by mitochondrial
      COX1 gene sequence analysis.
AB  - Diphyllobothrium nihonkaiense has been reported in Korea as Diphyllobothrium
      latum because of their close morphologic resemblance. We have identified a human
      case of D. nihonkaiense infection using the mitochondrial cytochrome c oxidase
      subunit I (cox1) gene sequence analysis. On 18 February 2012, a patient who had
      consumed raw fish a month earlier visited our outpatient clinic with a long
      tapeworm parasite excreted in the feces. The body of the segmented worm was 2 m
      long and divided into the scolex (head) and proglottids. It was morphologically
      close to D. nihonkaiense and D. latum. The cox1 gene analysis showed 99.4%
      (340/342 bp) homology with D. nihonkaiense but only 91.8% (314/342 bp) homology
      with D. latum. The present study suggested that the Diphyllobothrium spp.
      infection in Korea should be analyzed with specific DNA sequence for an accurate
      species identification. 

PMID- 24039293
TI  - A case of Budd-Chiari syndrome associated with alveolar echinococcosis.
AB  - Although alveolar echinococcosis (AE) can cause a serious disease with high
      mortality and morbidity similar to malign neoplasms. A 62-year-old woman admitted
      to a hospital located in Sivas, Turkey, with the complaints of fatigue and right
      upper abdominal pain. On contrast abdominal CT, a 54*70*45 mm sized cystic lesion
      was detected in the left lobe of the liver that was seen to extend to the
      posterior mediastinum and invade the diaphragm, esophagus, and pericardium. The
      cystic lesion was seen to be occluding the inferior vena cava and left hepatic
      vein at the level where the hepatic veins poured into the inferior vena cava.
      Bilateral pleural effusion was also detected. We discussed this secondary Budd
      Chiari Syndrome (BCS) case, resulting from the AE occlusion of the left hepatic
      vein and inferior vena cava, in light of the information in literature. 

PMID- 24039294
TI  - Superoxide anion production by human neutrophils activated by Trichomonas
      vaginalis.
AB  - Neutrophils are the predominant inflammatory cells found in vaginal discharges of
      patients infected with Trichomonas vaginalis. In this study, we examined
      superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis.
      Human neutrophils produced superoxide anions when stimulated with either a lysate
      of T. vaginalis, its membrane component (MC), or excretory-secretory product
      (ESP). To assess the role of trichomonad protease in production of superoxide
      anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with
      a protease inhibitor cocktail before incubation with neutrophils. Superoxide
      anion production was significantly decreased by this treatment. Trichomonad
      growth was inhibited by preincubation with supernatants of neutrophils incubated
      for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production
      by neutrophils was stimulated by live trichomonads. These results indicate that
      the production of superoxide anions and MPO by neutrophils stimulated with T.
      vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis. 

PMID- 24039295
TI  - IgG western blot for confirmatory diagnosis of equivocal cases of toxoplasmosis
      by EIA-IgG and fluorescent antibody test.
AB  - The performance values of available techniques used in serodiagnosis of
      toxoplasmosis are satisfactory but they raise problems of equivocal and
      discordant results for very low IgG titers. Recently marketed, LDBio-Toxo II IgG
      Western blot (IB) showed an excellent correlation with the dye test. We estimated
      the proportion of equivocal and discordant results between the enzyme immunoassay
      Platelia Toxo IgG (EIA-IgG) and fluorescent antibody test (FAT) and assessed the
      usefulness of the IB as a confirmatory test. Out of 2,136 sera collected from
      pregnant women, 1,644 (77.0%) tested unequivocally positive and 407 (19.0%) were
      negative in both EIA-IgG and FAT. The remaining 85 (4%) sera showed equivocal or
      discordant results. Among them, 73 (85.9%) were positive and 12 (14.1%) were
      negative in IB. Forty-one (89.1%) equivocal sera in EIA-IgG and 46 (86.8%)
      equivocal sera in FAT were positive in IB. Reducing the cut-off values of both
      screening techniques improved significantly their sensitivity in detecting very
      low IgG titers at the expense of their specificity. In conclusion, equivocal
      results in routine-used techniques and their discordance in determination of the
      immune status in pregnancy women were not uncommon. IB test appeard to be highly
      useful in these situations as a confirmatory technique. 

PMID- 24039296
TI  - Paleoparasitological surveys for detection of helminth eggs in archaeological
      sites of Jeolla-do and Jeju-do.
AB  - A paleoparasitological survey to detect helminth eggs was performed in
      archaeological sites of Jeolla-do and Jeju-do, the Republic of Korea. Total 593
      soil samples were collected in 12 sites of Jeolla-do and 5 sites of Jeju-do from
      April to November 2011, and examined by the methods of Pike and coworkers. A
      total of 4 helminth eggs, 2 eggs each for Trichuris trichiura and Ascaris sp.,
      were found in soil samples from 1 site, in Hyangyang-ri, Jangheung-eup, Jangheung
      gun, Jeollanam-do. The egg-recovery layer was presumed to represent a 19th
      century farm, which fact suggested the use of human manures. This is the third
      archaeological discovery of parasite eggs in Jeolla-do. Additionally, no helminth
      eggs in archaeological sites of Jeju-do is an interesting problem to be solved in
      the further investigations. 

PMID- 24039297
TI  - The phylogenetic significance of colour patterns in marine teleost larvae.
AB  - Ichthyologists, natural-history artists, and tropical-fish aquarists have
      described, illustrated, or photographed colour patterns in adult marine fishes
      for centuries, but colour patterns in marine fish larvae have largely been
      neglected. Yet the pelagic larval stages of many marine fishes exhibit subtle to
      striking, ephemeral patterns of chromatophores that warrant investigation into
      their potential taxonomic and phylogenetic significance. Colour patterns in
      larvae of over 200 species of marine teleosts, primarily from the western
      Caribbean, were examined from digital colour photographs, and their potential
      utility in elucidating evolutionary relationships at various taxonomic levels was
      assessed. Larvae of relatively few basal marine teleosts exhibit erythrophores,
      xanthophores, or iridophores (i.e. nonmelanistic chromatophores), but one or more
      of those types of chromatophores are visible in larvae of many basal marine
      neoteleosts and nearly all marine percomorphs. Whether or not the presence of
      nonmelanistic chromatophores in pelagic marine larvae diagnoses any major teleost
      taxonomic group cannot be determined based on the preliminary survey conducted,
      but there is a trend toward increased colour from elopomorphs to percomorphs.
      Within percomorphs, patterns of nonmelanistic chromatophores may help resolve or
      contribute evidence to existing hypotheses of relationships at multiple levels of
      classification. Mugilid and some beloniform larvae share a unique ontogenetic
      transformation of colour pattern that lends support to the hypothesis of a close
      relationship between them. Larvae of some tetraodontiforms and lophiiforms are
      strikingly similar in having the trunk enclosed in an inflated sac covered with
      xanthophores, a character that may help resolve the relationships of these
      enigmatic taxa. Colour patterns in percomorph larvae also appear to diagnose
      certain groups at the interfamilial, familial, intergeneric, and generic levels.
      Slight differences in generic colour patterns, including whether the pattern
      comprises xanthophores or erythrophores, often distinguish species. The homology,
      ontogeny, and possible functional significance of colour patterns in larvae are
      discussed. Considerably more investigation of larval colour patterns in marine
      teleosts is needed to assess fully their value in phylogenetic reconstruction.

PMID- 24039298
TI  - A Bayesian Approach for Estimating Mediation Effects with Missing Data.
AB  - Methodologists have developed mediation analysis techniques for a broad range of
      substantive applications, yet methods for estimating mediating mechanisms with
      missing data have been understudied. This study outlined a general Bayesian
      missing data handling approach that can accommodate mediation analyses with any
      number of manifest variables. Computer simulation studies showed that the
      Bayesian approach produced frequentist coverage rates and power estimates that
      were comparable to those of maximum likelihood with the bias-corrected bootstrap.
      We share a SAS macro that implements Bayesian estimation and use two data
      analysis examples to demonstrate its use.

PMID- 24039299
TI  - Analytical Study of Performance of Linear Discriminant Analysis in Stochastic
      Settings.
AB  - This paper provides exact analytical expressions for the first and second moments
      of the true error for linear discriminant analysis (LDA) when the data are
      univariate and taken from two stochastic Gaussian processes. The key point is
      that we assume a general setting in which the sample data from each class do not
      need to be identically distributed or independent within or between classes. We
      compare the true errors of designed classifiers under the typical i.i.d. model
      and when the data are correlated, providing exact expressions and demonstrating
      that, depending on the covariance structure, correlated data can result in
      classifiers with either greater error or less error than when training with
      uncorrelated data. The general theory is applied to autoregressive and moving
      average models of the first order, and it is demonstrated using real genomic
      data.

PMID- 24039300
TI  - Investigating the Release of a Hydrophobic Peptide from Matrices of Biodegradable
      Polymers: An Integrated Method Approach.
AB  - The objectives of this work were: (1) to select suitable compositions of tyrosine
      derived polycarbonates for controlled delivery of voclosporin, a potent drug
      candidate to treat ocular diseases, (2) to establish a structure-function
      relationship between key molecular characteristics of biodegradable polymer
      matrices and drug release kinetics, and (3) to identify factors contributing in
      the rate of drug release. For the first time, the experimental study of polymeric
      drug release was accompanied by a hierarchical sequence of three computational
      methods. First, suitable polymer compositions used in subsequent neural network
      modeling were determined by means of response surface methodology (RSM). Second,
      accurate artificial neural network (ANN) models were built to predict drug
      release profiles for fifteen polymers located outside the initial design space.
      Finally, thermodynamic properties and hydrogen-bonding patterns of model drug
      polymer complexes were studied using molecular dynamics (MD) technique to
      elucidate a role of specific interactions in drug release mechanism. This
      research presents further development of methodological approaches to meet
      challenges in the design of polymeric drug delivery systems.

PMID- 24039302
TI  - The Role of Social Capital in Educational Aspirations of Rural Youth.
AB  - Drawing on a recent national survey of rural high school students, this study
      investigated the relationship between social capital and educational aspirations
      of rural youth. Results showed that various process features of family and school
      social capital were important to predict rural youth's educational aspirations
      beyond sociodemographic background. In particular, parents' and teachers'
      educational expectations for their child and student respectively were positively
      related to educational aspirations of rural youth. In addition, discussion with
      parents about college was positively related to educational aspirations of rural
      youth. On the other hand, there was little evidence to suggest that number of
      siblings and school proportions of students on free lunch and minority students
      are related to educational aspirations of rural youth, after controlling for the
      other variables. The authors highlight unique features of rural families,
      schools, and communities that may combine to explain the complexity of the role
      of social capital in shaping educational aspirations of rural youth.

PMID- 24039301
TI  - Discounting of Various types of rewards by women with and without binge eating
      Disorder: Evidence for general rather than specific Differences.
AB  - The present study compared the extent to which obese women with binge eating
      disorder (BED), obese women without BED, and controls discounted delayed and
      probabilistic money and directly consumable rewards: food, massage time, and
      preferred sedentary activity. Of special interest was whether the BED group
      differed from the other groups in terms of their discounting of all three types
      of directly consumable rewards or only in their discounting of food. Overall, the
      BED group tended to discount both delayed and probabilistic rewards of all types
      more steeply than the obese and control groups. Thus, rather than finding
      differences specific to particular types of rewards, we find that women with BED
      are generally more impatient when choices involve delayed rewards and more risk
      averse when they involve probabilistic rewards. These results suggest a
      temperamental difference associated with BED that cannot be accounted for by the
      concomitant obesity.

PMID- 24039303
TI  - Esterification Catalysis by Pyridinium p-Toluenesulfonate Revisited-Modification
      with a Lipid Chain for Improved Activities and Selectivities.
AB  - The lipid analogues of pyridinium p-toluenesulfonate (PPTS) were examined for
      catalyzing the condensation of an equimolar mixture of carboxylic acids and
      alcohols under mild conditions without removal of water. Although PPTS is a poor
      catalyst, the introduction of a lipid chain and nitro group significantly
      improved the activity of PPTS and led to selectivity at suppressing elimination
      side reactions of alcohols. 2-Oleamido-5-nitro-pyridinium p-toluenesulfonate (6)
      is a lead catalyst that promoted various esterification reactions with yields up
      to 99%.

PMID- 24039304
TI  - Enantiodivergent Hydroboration Reactions of a Racemic Allenylsilane with
      Diisopinocampheylborane and Curtin-Hammett Controlled Double Asymmetric
      Crotylboration Reactions of (S)-E-alpha-phenyldimethylsilyl( d diisopinocampheyl)
      crotylborane.
AB  - The enantiodivergent hydroboration reactions of racemic allenylsilane (+/-)-4
      with ( d Ipc)2BH and subsequent crotylboration of achiral aldehydes with the
      product crotylborane (S)-E-5 at -78  degrees C provide (E)-delta-silyl-anti
      homoallylic alcohols 6 in 71-89% yield and with 93-96% ee. Intriguingly,
      mismatched double asymmetric crotylboration reactions of enantioenriched chiral
      aldehydes 20 with (S)-E-5 proceed under Curtin-Hammett control to give anti-3
      hydroxylcrotylsilanes 24 as the only products.

PMID- 24039305
TI  - Direct, Enantioselective Synthesis of Pyrroloindolines and Indolines From Simple
      Indole Derivatives.
AB  - The (R)-BINOL*SnCl4-catalyzed formal (3 + 2) cycloaddition between 3-substituted
      indoles and benzyl 2-trifluoroacetamidoacrylate is a direct, enantioselective
      method to prepare pyrroloindolines from simple starting materials. However, under
      the originally disclosed conditions, the pyrroloindolines are formed as mixtures
      of diastereomers, typically in the range of 3:1 to 5:1 favoring the exo-product.
      The poor diastereoselectivity detracts from the synthetic utility of the
      reaction. We report here that use of methyl 2-trifluoroacetamidoacrylate in
      conjunction with (R)-3,3'-dichloro-BINOL*SnCl4 provides the corresponding
      pyrroloindolines with improved diastereoselectivity (typically >=10:1). Guided by
      mechanistic studies, a one-flask synthesis of enantioenriched indolines by in
      situ reduction of a persistent iminium ion is also described.

PMID- 24039306
TI  - A room temperature copper catalyzed N-selective arylation of beta-amino alcohols
      with iodoanilines and aryl iodides.
AB  - An efficient method is described for the synthesis of N-(2-aminophenyl)-2
      hydroxyethylamines via a copper catalyzed N-selective arylation of beta-amino
      alcohols with iodoanilines. The corresponding coupling products are useful
      intermediates for the synthesis of a variety of N-2-hydroxyethyl-substituted
      benzimidazoles, benzimidazolones, and iminobenzimidazoles. We found that 2
      iodoaniline only arylates certain amino alcohols but not amines lacking a
      hydroxyl group. We also demonstrate the arylation of sterically demanding beta
      amino alcohols, such as ephedrine and prolinol with aryl iodides at room
      temperature.

PMID- 24039307
TI  - Design and synthesis of 3,5-disubstituted boron-containing 1,2,4-oxadiazoles as
      potential combretastatin A-4 (CA-4) analogs.
AB  - We have designed and synthesized a small library of 3,5-disubstituted-1,2,4
      oxadiazole containing combretastatin A-4 (CA-4) analogs. Our objective is to
      increase the efficacy of the CA-4 as an anti-tubulin and antimitotic agent by
      substituting the cis-alkene bond with one of its bioisosteres, the 1,2,4
      oxadiazole ring. We also modified the substituents attached to both of the phenyl
      rings (ring A and B in Fig. 1) of CA-4 for the purpose of diversifying our
      analogs based on SAR. These compounds were synthesized via a coupling reaction
      between an amidoxime and a carboxylic acid in DMF solvent, with HOBt as a base,
      and utilizing EDCI as a coupling reagent. Using this protocol, we synthesized a
      small library of 10 compounds with moderate to good yields. A detailed biological
      study is currently undergoing in our laboratory to evaluate the activity of these
      compounds.

PMID- 24039308
TI  - A general, enantioselective synthesis of beta- and gamma-fluoroamines.
AB  - In this Letter, we describe a short, high yielding protocol for the
      enantioselective (87-96% ee) and general synthesis of beta-fluoroamines and
      previously difficult to access gamma-fluoroamines from commercial aldehydes via
      organocatalysis.

PMID- 24039309
TI  - Chemoselective hydroamination of vinyl arenes catalyzed by an NHC-amidate
      alkoxide Pd(II) complex and p-TsOH.
AB  - The hydroamination of various substituted vinyl arenes with benzenesulfonamide
      was explored using an NHC-amidate-alkoxide palladium catalyst in conjunction with
      p-TsOH. Utilizing halide-substituted and electron-rich vinyl arenes, this
      methodology selectively furnished the cross-coupled hydroamination products in
      moderate to excellent yields in a Markovnikov fashion while greatly reducing
      undesired acid-catalyzed homocoupling of the vinyl arenes. Electron-rich vinyl
      arenes typically required milder conditions than electron-poor ones. While most
      effective for para-substituted substrates, the catalyst system also furnished the
      desired products from ortho- and meta-substituted vinyl arenes with high
      chemoselectivities.

PMID- 24039310
TI  - Is the Belief in Meritocracy Palliative for Members of Low Status Groups?
      Evidence for a Benefit for Self-Esteem and Physical Health via Perceived Control.
AB  - Consensually held ideologies may serve as the cultural "glue" that justifies
      hierarchical status differences in society (e.g. Augustinos, 1998). Yet to be
      effective these beliefs need to be embraced by low-status groups. Why would
      members of low-status groups endorse beliefs that justify their relative
      disadvantage? We propose that members of low-status groups in the United States
      may benefit from some system-justifying beliefs (such as the belief in
      meritocracy) to the extent that these beliefs emphasize the perception of control
      over future outcomes. In 2 studies, among women, lower-SES women, and women of
      color, we found a positive relationship between the belief in meritocracy and
      well-being (self-esteem and physical health) that was mediated by perceived
      control. Members of low-status groups may benefit from some system-justifying
      beliefs to the extent that these beliefs, like the belief in meritocracy,
      emphasize the perception of control over future outcomes.

PMID- 24039311
TI  - Teenage childbirth and young adult criminal convictions: A quasi-experimental
      study of criminal outcomes for teenage mothers.
AB  - PURPOSE: Teenage childbirth is associated with poor psychosocial outcomes for
      teen mothers. One example is that teen mothers have higher rates of antisocial
      behavior. The extant research has not been able to determine if teenage
      motherhood is independently associated with criminal behavior, or if the
      association is due to selection factors associated with both teenage childbirth
      and criminal behavior. METHODS: We used longitudinal data from Swedish national
      registers and sibling-comparisons (both full- and half-siblings) to identify the
      extent to which there is an independent association between teenage childbirth
      and mothers' likelihood of criminal conviction between ages 20-30, or if the
      association is confounded by familial (including genetic or environmental)
      factors that make sisters similar. RESULTS: Women who began childbearing as
      teenagers were more likely to be convicted of a crime in young adulthood compared
      to women who delayed childbearing. When sisters were compared, the association
      between teenage childbirth and criminal convictions disappeared. Multivariate
      behavior genetic analyses suggest genetic and shared environmental account for
      the association. CONCLUSIONS: The statistical association between teenage
      childbirth and early adulthood criminal convictions is confounded by genetic and
      shared environmental factors that influence both the likelihood of teenage
      childbirth and risk of early adulthood criminal conviction.

PMID- 24039312
TI  - Does Retiree Health Insurance Encourage Early Retirement?
AB  - The strong link between health insurance and employment in the United States may
      cause workers to delay retirement until they become eligible for Medicare at age
      65. However, some employers extend health insurance benefits to their retirees,
      and individuals who are eligible for such retiree health benefits need not wait
      until age 65 to retire with group health coverage. We investigate the impact of
      retiree health insurance on early retirement using employee-level data from 54
      diverse firms that are clients of Towers Watson, a leading benefits consulting
      firm. We find that retiree health coverage has its strongest effects at ages 62
      through 64. Coverage that includes an employer contribution is associated with a
      6.3 percentage point (36.2 percent) increase in the probability of turnover at
      age 62, a 7.7 percentage point (48.8 percent) increase in the probability of
      turnover at age 63, and a 5.5 percentage point (38.0 percent) increase in the
      probability of turnover at age 64. Conditional on working at age 57, such
      coverage reduces the expected retirement age by almost three months and reduces
      the total number of person-years worked between ages 58 and 64 by 5.6 percent.

PMID- 24039313
TI  - Asymptotic Properties of the Sequential Empirical ROC, PPV and NPV Curves Under
      Case-Control Sampling.
AB  - The receiver operating characteristic (ROC) curve, the positive predictive value
      (PPV) curve and the negative predictive value (NPV) curve are three measures of
      performance for a continuous diagnostic biomarker. The ROC, PPV and NPV curves
      are often estimated empirically to avoid assumptions about the distributional
      form of the biomarkers. Recently, there has been a push to incorporate group
      sequential methods into the design of diagnostic biomarker studies. A thorough
      understanding of the asymptotic properties of the sequential empirical ROC, PPV
      and NPV curves will provide more flexibility when designing group sequential
      diagnostic biomarker studies. In this paper we derive asymptotic theory for the
      sequential empirical ROC, PPV and NPV curves under case-control sampling using
      sequential empirical process theory. We show that the sequential empirical ROC,
      PPV and NPV curves converge to the sum of independent Kiefer processes and show
      how these results can be used to derive asymptotic results for summaries of the
      sequential empirical ROC, PPV and NPV curves.

PMID- 24039314
TI  - On the similarity between exchangeable profiles: A psychometric model, analytic
      strategy, and empirical illustration.
AB  - Analyses of profile similarity are widespread in personality psychology, but
      their apparent simplicity masks difficult psychometric and statistical issues. We
      present a psychometric framework that addresses an important challenge (i.e.,
      profile normativeness) in examinations of dyadic exchangeable profiles. In
      addition, we present an analytic strategy accounting for non-independence that
      often arises in analyses of profile similarity, facilitating integrated
      examinations of variables at dyadic and individual levels. An empirical analysis
      of personality similarity and relationship quality demonstrates that the model
      and analytic strategy can reveal novel psychological insights. These are
      important advances, as previous work has ignored exchangeable profiles and has
      failed to present an integrated psychometric and statistical framework for
      profile similarity.

PMID- 24039316
TI  - Thick-Market Effects and Churning in the Labor Market: Evidence from U.S. Cities.
AB  - Using U.S. Census microdata, we show that, on average, workers change occupation
      and industry less in more densely populated areas. The result is robust to
      standard demographic controls, as well as to including aggregate measures of
      human capital and sectoral mix. Analysis of the displaced worker surveys shows
      that this effect is present in cases of involuntary separation as well. On the
      other hand, we actually find the opposite result (higher rates of occupational
      and industrial switching) for the subsample of younger workers. These results
      provide evidence in favor of increasing-returns-to-scale matching in labor
      markets. Results from a back-of-the-envelope calibration suggest that this
      mechanism has an important role in raising both wages and returns to experience
      in denser areas.

PMID- 24039315
TI  - Personality Stability from Childhood to Midlife: Relating Teachers' Assessments
      in Elementary School to Observer- and Self-Ratings 40 Years Later.
AB  - We report on the longitudinal stability of personality traits across an average
      40 years in the Hawaii Personality and Health Cohort relating childhood teacher
      assessments of personality to adult self- and observer- reports. Stabilities
      based on self-ratings in adulthood were compared to those measured by the
      Structured Interview for the Five-Factor Model (SIFFM; Trull & Widiger, 1997),
      and trait ratings completed by interviewers. Although convergence between self
      reports and observer-ratings was modest, childhood traits demonstrated similar
      levels of stability across methods in adulthood. Extraversion and
      Conscientiousness generally showed higher stabilities, whereas Neuroticism showed
      none. For Agreeableness and Intellect/Openness, stability was highest when
      assessed with observer-ratings. These findings are discussed in terms of
      differences in trait evaluativeness and observability across measurement methods.

PMID- 24039317
TI  - Viscometric Studies in Dilute Solution Mixtures of Chitosan and Microcrystalline
      Chitosan with Poly(vinyl alcohol).
AB  - The viscosity behavior of aqueous mixtures formed by a polyelectrolyte (A) and a
      neutral polymer (B), such as chitosan/poly(vinyl alcohol) (Ch/PVA) and
      microcrystalline chitosan/poly(vinyl alcohol) (MCCh/PVA), have been investigated
      at 25  degrees C. The intrinsic viscosity and the viscosity interaction parameter
      of each polymer in 0.1 mol.dm-3 CH3COOH/0.2 mol.dm-3 NaCl solution as well as the
      ternary systems (polymer A/polymer B/solvent) have been determined and have
      served for estimation of the miscibility of different polymer mixtures by means
      of the method of classical dilution. By comparing the experimental and ideal
      viscosity data it is clearly seen that the satisfaction of the miscibility
      criterion depends on the definition of the ideal parameter [Formula: see text].
      If the [Formula: see text] parameter is defined according to the Krigbaum-Wall
      criterion and Garcia criterion, the investigated blends of Ch/PVA satisfy the
      miscibility criterion. In the case of MCCh/PVA blends, the polymeric components
      show poor miscibility. Additionally, the viscosity results show that the degree
      of miscibility depends on the molecular weight of chitosan and on the degree of
      PVA hydrolysis.

PMID- 24039318
TI  - The impact of desegregation on black teachers in the metropolis, 1970-2000.
AB  - One-third of public school students are racial and/or ethnic minorities. Yet only
      14 per cent of teachers represent these groups. Frequently lost in broader
      debates concerning this disparity is the paradoxical contribution of the 1954
      Brown v. Board of Education decision. Schools were mandated under Brown to
      desegregate the student body. But the law did not necessarily protect the jobs of
      black teachers and administrators. Using a unique database of court orders, we
      examine the impact of mandated desegregation on black teachers. Findings indicate
      regional differences. Mandated desegregation created conditions that resulted in
      decreases in the black teaching force in the South. The opposite occurred in the
      nonsouth, with mandated desegregation positively associated with increases
      (although small) in the black teaching force. Our findings suggest that the
      legacy of mandated desegregation may have created broader institutional
      conditions in which black and other minority teachers remain underrepresented in
      the teaching force.

PMID- 24039319
TI  - Comparison of standard laminectomy with an optimized ejection method for the
      removal of spinal cords from rats and mice.
AB  - For researchers seeking to collect spinal cord samples from mice and rats while
      avoiding acid decalcification, few options are available. Laminectomy is the
      standard method which yields high quality samples, yet is time consuming and
      technically difficult. Ejection of the cord from the vertebral column is another
      technique commonly used; however, the literature suggests that this method can
      damage the spinal tissues and is typically avoided when histology of samples is
      the desired endpoint. Here, we describe an optimized method for ejection of
      spinal cords from rats and mice, and compare histological quality of these
      samples with those collected via laminectomy. Our results show that ejection can
      yield high quality spinal cord samples and may be suitable for use as an
      alternative to laminectomy.

PMID- 24039320
TI  - Auxiliary marker-assisted classification in the absence of class identifiers.
AB  - Constructing classification rules for accurate diagnosis of a disorder is an
      important goal in medical practice. In many clinical applications, there is no
      clinically significant anatomical or physiological deviation exists to identify
      the gold standard disease status to inform development of classification
      algorithms. Despite absence of perfect disease class identifiers, there are
      usually one or more disease-informative auxiliary markers along with feature
      variables comprising known symptoms. Existing statistical learning approaches do
      not effectively draw information from auxiliary prognostic markers. We propose a
      large margin classification method, with particular emphasis on the support
      vector machine (SVM), assisted by available informative markers in order to
      classify disease without knowing a subject's true disease status. We view this
      task as statistical learning in the presence of missing data, and introduce a
      pseudo-EM algorithm to the classification. A major distinction with a regular EM
      algorithm is that we do not model the distribution of missing data given the
      observed feature variables either parametrically or semiparametrically. We also
      propose a sparse variable selection method embedded in the pseudo-EM algorithm.
      Theoretical examination shows that the proposed classification rule is Fisher
      consistent, and that under a linear rule, the proposed selection has an oracle
      variable selection property and the estimated coefficients are asymptotically
      normal. We apply the methods to build decision rules for including subjects in
      clinical trials of a new psychiatric disorder and present four applications to
      data available at the UCI Machine Learning Repository.

PMID- 24039321
TI  - Correlates and predictors of parenting stress among internationally adopting
      mothers: A longitudinal investigation.
AB  - This study examined correlates and predictors of parenting stress among
      internationally adopting (IA) mothers with the goal of expanding the knowledge
      base on the experiences of adoptive parents. One hundred and forty-three IA
      mothers completed pre-adoption (Time 0) and six months post-adoption (Time 1)
      surveys with questions regarding child-, parent-, and family-related
      characteristics. Mother reports of higher depression symptoms, higher
      expectations of child developmental and behavioral/emotional problems, and a
      greater number of children in the family at pre-adoption were significantly
      related to higher parenting stress six months post-adoption. In contrast, mother
      reports of higher expectations for child acceptance and higher perceived social
      support at pre-adoption were significantly related to lower parenting stress six
      months post-adoption. Higher maternal depression symptoms, higher expectations of
      child behavior/emotional problems, and a greater number of children in the family
      at pre-adoption together accounted for 22% of the variance in parenting stress
      six months post-adoption. Concurrent higher maternal depression symptoms and
      higher reports of child behavioral/emotional problems predicted higher parenting
      stress six months post-adoption over and above pre-adoption predictors, and
      accounted for an additional 33% of the variance. Results and directions for
      future research are discussed from a transactional perspective, with particular
      emphasis on the importance of pre-adoptive information for adoption research and
      practice.

PMID- 24039322
TI  - A random effects epidemic-type aftershock sequence model.
AB  - We consider an extension of the temporal epidemic-type aftershock sequence (ETAS)
      model with random effects as a special case of a well-known doubly stochastic
      self-exciting point process. The new model arises from a deterministic function
      that is randomly scaled by a nonnegative random variable, which is unobservable
      but assumed to follow either positive stable or one-parameter gamma distribution
      with unit mean. Both random effects models are of interest although the one
      parameter gamma random effects model is more popular when modeling associated
      survival times. Our estimation is based on the maximum likelihood approach with
      marginalized intensity. The methods are shown to perform well in simulation
      experiments. When applied to an earthquake sequence on the east coast of Taiwan,
      the extended model with positive stable random effects provides a better model
      fit, compared to the original ETAS model and the extended model with one
      parameter gamma random effects.

PMID- 24039323
TI  - Synthesis and characterization of antiseptic-based poly(anhydride-esters).
AB  - Poly(anhydride-esters) were prepared from catechol, fenticlor and
      hexachlorophene. The molecular weights (Mw) of the polymers were typically >
      10,000 Da with glass transition temperatures (Tg) ranging from 23 to 84  degrees
      C. The thermal characteristics of the polymers paralleled the melting
      temperatures of the chemically incorporated antiseptic molecules. The in vitro
      release of the chemically incorporated antiseptic molecules were monitored over a
      12 week period. For comparison, the in vitro release of physically admixed
      antiseptic molecules were also observed. After 12 weeks, the polymers were not
      completely degraded with drug release ranging from less than 1 to 55 %. Sessile
      drop contact angles indicated that the polymers were relatively hydrophobic,
      contributing to the slow polymer degradation rates.

PMID- 24039324
TI  - Community violence exposure, coping, and problematic alcohol and drug use among
      urban, female caregivers: A prospective study.
AB  - Victimization is associated with substance use in women, but less is known about
      linkages between witnessing community violence and substance use, even though
      more women witness versus directly experience violence. Further, factors that
      contribute to or protect against women's problematic substance use are less well
      understood. Urban female caregivers (N = 318; > 92% African American/black)
      living in low-income communities were interviewed annually for three waves
      regarding exposure to community violence, coping behaviors, substance use, and
      protective factors. Path analyses revealed that lifetime witnessing of violence,
      but not victimization, assessed at baseline, was associated with changes in
      avoidant coping, but not active coping, one year later; avoidant coping, in turn,
      was related to changes in and higher levels of problematic drug use the following
      year. Victimization was directly related to problematic drug use, but not to
      alcohol use. Regression analyses indicated that high levels of religious
      commitment and social support at baseline were prospectively associated with
      lower levels of avoidant coping. Because caregivers are important role models for
      their children, it is important to attend to the factors that contribute to their
      substance use and abuse.

PMID- 24039325
TI  - Social Problem-Solving in Early Childhood: Developmental Change and the Influence
      of Shyness.
AB  - The purpose of this study was to examine developmental change and the influence
      of shyness on social problem-solving (SPS). At 24, 36, and 48 months, children
      (N=570) were observed while interacting with an unfamiliar peer during an SPS
      task and at 24 months, maternal report of shyness was collected. Results showed
      that across the full sample, children displayed low but stable levels of
      withdrawn SPS and increasing levels of SPS competence over development. In
      addition, results showed that 24-month shyness was associated with high
      increasing and high-decreasing withdrawn SPS trajectories compared to the low
      increasing withdrawn SPS trajectory. Shyness was also associated with the low
      increasing compared to the high-increasing SPS competence trajectory. Findings
      demonstrate the development of SPS competence over early childhood, as well as
      the influence of early shyness on this developmental course, with some shy
      children showing improvement in SPS skills and others continuing to show SPS
      difficulties over time.

PMID- 24039326
TI  - Transfer Learning for Activity Recognition: A Survey.
AB  - Many intelligent systems that focus on the needs of a human require information
      about the activities being performed by the human. At the core of this capability
      is activity recognition, which is a challenging and well-researched problem.
      Activity recognition algorithms require substantial amounts of labeled training
      data yet need to perform well under very diverse circumstances. As a result,
      researchers have been designing methods to identify and utilize subtle
      connections between activity recognition datasets, or to perform transfer-based
      activity recognition. In this paper we survey the literature to highlight recent
      advances in transfer learning for activity recognition. We characterize existing
      approaches to transfer-based activity recognition by sensor modality, by
      differences between source and target environments, by data availability, and by
      type of information that is transferred. Finally, we present some grand
      challenges for the community to consider as this field is further developed.

PMID- 24039327
TI  - Identifying and Bounding Ethnic Neighborhoods.
AB  - This study presents three novel approaches to the question of how best to
      identify ethnic neighborhoods (or more generally, neighborhoods defined any
      aspect of their population composition) and to define their boundaries. It takes
      advantage of unusual data on the residential locations of all residents of
      Newark, NJ, in 1880 to avoid having to accept arbitrary administrative units
      (like census tracts) as the building blocks of neighborhoods. For theoretical
      reasons the street segment is chosen as the basic unit of analysis. All three
      methods use information on the ethnic composition of buildings or street segments
      and the ethnicity of their neighbors. One approach is a variation of k-functions
      calculated for each adult resident, which are then subjected to a cluster
      analysis to detect discrete patterns. The second is an application of an energy
      minimization algorithm commonly used to enhance digital images. The third is a
      Bayesian approach previously used to study county-level disability data. Results
      of all three methods depend on decisions about technical procedures and criteria
      that are made by the investigator. Resulting maps are roughly similar, but there
      is no one best solution. We conclude that researchers should continue to seek
      alternative methods, and that the preferred method depends on how one's
      conceptualization of neighborhoods matches the empirical approach.

PMID- 24039328
TI  - Evaluation of two methods for quantifying passeriform lice.
AB  - Two methods commonly used to quantify ectoparasites on live birds are visual
      examination and dust-ruffling. Visual examination provides an estimate of
      ectoparasite abundance based on an observer's timed inspection of various body
      regions on a bird. Dust-ruffling involves application of insecticidal powder to
      feathers that are then ruffled to dislodge ectoparasites onto a collection
      surface where they can then be counted. Despite the common use of these methods
      in the field, the proportion of actual ectoparasites they account for has only
      been tested with Rock Pigeons (Columba livia), a relatively large-bodied species
      (238-302 g) with dense plumage. We tested the accuracy of the two methods using
      European Starlings (Sturnus vulgaris; ~75 g). We first quantified the number of
      lice (Brueelia nebulosa) on starlings using visual examination, followed
      immediately by dust-ruffling. Birds were then euthanized and the proportion of
      lice accounted for by each method was compared to the total number of lice on
      each bird as determined with a body-washing method. Visual examination and dust
      ruffling each accounted for a relatively small proportion of total lice (14% and
      16%, respectively), but both were still significant predictors of abundance. The
      number of lice observed by visual examination accounted for 68% of the variation
      in total abundance. Similarly, the number of lice recovered by dust-ruffling
      accounted for 72% of the variation in total abundance. Our results show that both
      methods can be used to reliably quantify the abundance of lice on European
      Starlings and other similar-sized passerines.

PMID- 24039329
TI  - Activative Fathering Predicts Later Children's Behaviour Dysregulation and
      Sociability.
AB  - This study examined activative fathering observed during father-child
      interactions in the family home, focusing on the relation between activative
      fathering at child age 4 and children's behaviour dysregulation and sociability
      at child age 5. One hundred twenty-seven families participated in the study.
      Activative fathering was associated with later lower child dysregulation during a
      problem solving task, higher dysregulation during a wait task, and higher
      sociability in the home. Contrary to expectations, paternal control did not
      moderate these relations. Results are discussed in relation to father-child
      activation relationship theory.

PMID- 24039331
TI  - Quality assessment of medical education at faculty of medicine of sarajevo
      university - comparison of assessment between students in bologna process and old
      system of studying.
AB  - CONFLICT OF INTEREST: NONE DECLARED. INTRODUCTION: The quality of the teaching
      learning process at the universities in Bosnia and Herzegovina and abroad depends
      mainly of infrastructure that includes an optimal teaching space, personnel and
      equipment, in accordance with existing standards and norms. For the assessment of
      teaching at the faculties, the opinion of students is very important (4, 5).
      Students are often unhappy with the educational process. GOAL: To compare the
      results of the teaching process evaluation between students studying according to
      the Bologna system and the old system of education. MATERIAL AND METHODS: We used
      the questionnaire as a carrier of data created with variables relevant for
      assessing the success of the educational process at the Medical Faculty in
      Sarajevo. The survey was conducted among students of the sixth year of the
      Medical Faculty in Sarajevo. There were 103 students surveyed, of which 32 were
      studying according to the Bologna and 71 by the old concept of studies. RESULTS
      AND DISCUSSION: Results of survey which measured students satisfaction with the
      educational process (theoretical and practical instruction, interactive learning,
      testing, use of IT and technical aids in teaching, availability of instructional
      literature etc.) lead us to the conclusion that the lowest satisfaction is
      associated with factors depending on financial resources, specifically related to
      library funds and the degree of computerization of educational process, and also
      with the level of teachers capability to convey knowledge to students with the
      application of modern medical information technology and technical teaching aids.

PMID- 24039330
TI  - Reverse micelles as a tool for probing solvent modulation of protein dynamics:
      Reverse micelle encapsulated hemoglobin.
AB  - Hydration waters impact protein dynamics. Dissecting the interplay between
      hydration waters and dynamics requires a protein that manifests a broad range of
      dynamics. Proteins in reverse micelles (RMs) have promise as tools to achieve
      this objective because the water content can be manipulated. Hemoglobin is an
      appropriate tool with which to probe hydration effects. We describe both a
      protocol for hemoglobin encapsulation in reverse micelles and a facile method
      using PEG and cosolvents to manipulate water content. Hydration properties are
      probed using the water-sensitive fluorescence from Hb bound pyranine and
      covalently attached Badan. Protein dynamics are probed through ligand
      recombination traces derived from photodissociated carbonmonoxy hemoglobin on a
      log scale that exposes the potential role of both alpha and beta solvent
      fluctuations in modulating protein dynamics. The results open the possibility of
      probing hydration level phenomena in this system using a combination of NMR and
      optical probes.

PMID- 24039332
TI  - P300 evoked potential in patients with mild cognitive impairment.
AB  - CONFLICT OF INTEREST: NONE DECLARED. AIM: The aim of this study is to present
      differences of amplitude and latency of P300 wave between examinees with mild
      cognitive impairment and examinees from the control group. METHODS: A cross
      section study was performed between April 1(st) and July 10(th) 2012, with the
      diagnosis of mild cognitive impairment as the main criterion for inclusion. In
      the twenty-two examinees who participated in the research, mild cognitive
      impairment was confirmed by neuropsychological testing, following which they were
      subjected to the examination of auditory evoked potentials. The control group
      consisting of 22 examinees, for which the lack of the same diagnosis was
      previously ascertained, was also subjected to the examination of auditory evoked
      potentials. The main findings were the differences in the latency and amplitude
      size of P300 wave targeted and non-targeted stimuli. RESULTS: The latency of P300
      wave targeted stimuli in patients with mild cognitive impairment has, in
      statistical terms, proven to be significantly longer when compared to the control
      group. The average latency length in those with MCI amounted to 306.18 ms,
      whereas the latency in the control group came to 295.95 ms. Similarly, the
      latency length of non-targeted stimuli turned out to be statistically higher,
      with the length of 320.00 ms in the former group, and 301.36 ms in the latter.
      Amplitudes in patients with mild cognitive impairment were lower in comparison to
      the control group, with extremely low amplitudes recorded in 36.36% of patients.
      CONCLUSION: In patients with mild cognitive impairment extended latency and lower
      amplitude of P300 wave are recorded.

PMID- 24039333
TI  - Evaluation of the biocompatibility of silicone gel implants - histomorphometric
      study.
AB  - CONFLICT OF INTEREST: NONE DECLARED Breast implants are medical devices that are
      used to augment breast size or to reconstruct the breast following mastectomy or
      to correct a congenital abnormality. Breast implants consist of a silicone outer
      shell and a filler (most commonly silicone gel or saline). Approximately 5 to 10
      million women worldwide have breast implants. Histomorphometric study to evaluate
      the biological tissue compatibility of silicone implants suitable for plastic
      surgery and the adverse effects and risks of this material. Thirty Wistar white
      rats received subcutaneous implants and the revestiment of silicone gel Silimed
      (r)(r), and randomized into six groups of five animals each, according to the
      type of implanted material and the time of sacrifice. Eight areas of 60.11mm2
      corresponding to the obtained surgical pieces were analyzed, counting mesenchymal
      cells, eosinophils, and foreign body giant cells, observing an acceptable
      biocompatibility in all implants, for subsequent statistical analysis by Tukey
      test. Silicone gel showed inflammation slightly greater than for other groups,
      with tissue reactions varying from light to moderate, whose result was the
      formation of a fibrous capsule around the material, recognized by the organism as
      a foreign body. Despite frequent local complications and adverse outcomes, this
      research showed that the silicone and top layer presented an acceptable chronic
      inflammatory reaction, which did not significantly differ from the control group.
      In general, it is possible to affirm that silicone gel had acceptable levels of
      biocompatibility, confirmed the rare presence of foreign body giant cells, and
      when of the rupture, formed a fibrous capsule around the material, separating the
      material of the organism.

PMID- 24039334
TI  - A proposed defect tracking model for classifying the inserted defect reports to
      enhance software quality control.
AB  - CONFLICT OF INTEREST: NONE DECLARED Defect tracking systems play an important
      role in the software development organizations as they can store historical
      information about defects. There are many research in defect tracking models and
      systems to enhance their capabilities to be more specifically tracking, and were
      adopted with new technology. Furthermore, there are different studies in
      classifying bugs in a step by step method to have clear perception and applicable
      method in detecting such bugs. This paper shows a new proposed defect tracking
      model for the purpose of classifying the inserted defects reports in a step by
      step method for more enhancement of the software quality.

PMID- 24039335
TI  - Left ventricular diastolic dysfunction in asymptomatic type 2 diabetic patients:
      detection and evaluation by tissue Doppler imaging.
AB  - CONFLICT OF INTEREST: NONE DECLARED The aim of the study was detection of
      diastolic dysfunction of myocardium with Tissue Doppler Imaging (TDI) in
      asymptomatic type 2 diabetic patients, in five years duration of disease, and
      normal cardiac function on conventional echocardiography (CE), according to the
      performance showed on exercise stress test. MATERIAL AND METHODS: We studied 300
      patients, of them 150 patients with non-obese, normotensive, uncomplicated type 2
      diabetes, in five years duration of disease and 150 healthy control subjects. Of
      all patients, 100 with type 2 diabetes, and 100 patients from the control group
      underwent exercise test on a treadmill. All participants underwent both CE and
      TDI echocardiography. With TDI, lateral E' peak velocity, atrial velocity (A'),
      their ratio (E'/A') and systolic velocity (S') were measured. Diastolic
      dysfunction was diagnosed by tissue Doppler imaging, and the following criterion
      was met: E'/A' ratio <1. Cardiac function with CE was without significant
      features in the two groups. RESULTS AND DISCUSSION: Using TDI interrogation,
      diabetic subjects showed a lower E' velocity (10,75+/-1,2 vs. 14+/-3 cm/s,
      p<0,001), an increased A' velocity (10,65+/-1,8 vs. 11+/-3 cm/s, p<0,02), and a
      reduced E/A ratio (0,82+/-0,04 vs. 1,17+/-1,4, p<0,001), S (8.92+/-3,80 vs.
      9,30+/-3.30 cm/sec); E/A (1,17+/-0.55, p<0,01). In diabetic patients, after the
      exercise stress test performance, the myocardial velocity increase is registered
      for wave E'=1,27 cm/sec (12,01%), for wave A'=1,7 cm/sec (15,9%), reduced ratio
      E'/A' (0.89+/-0,1 cm/sec 9,0%) and S'=1,3 cm/sec (14,77%). Whereas, mean
      myocardial velocity values in examined control group after the exercise stress
      test were higher as follows: E'=2,7 cm/sec (19%), A'=2,1 cm/sec (14%), E'/A'=0,8
      cm/sec (12%), and S'=2,7 cm/sec (18%). Myocardial diastolic dysfunction due to
      reduced exercise tolerance can be evidenced by TDI in type 2 diabetic subjects,
      even in the presence of a normal cardiac function with CE and symptom free
      diabetic patients in rest. Therefore, our findings could justify the use of
      Tissue Doppler imaging for diastolic function assessment in diabetics with
      otherwise non significant features on CE.

PMID- 24039336
TI  - Assessment of Diabetic Polyneuropathy in Inpatient Care: Fasting Blood Glucose,
      HbA1c, Electroneuromyography and Diabetes Risk Factors.
AB  - CONFLICT OF INTEREST: NONE DECLARED. GOAL: THE GOALS OF THIS STUDY ARE TO: a)
      determine the prevalence of diabetic polyneuropathy (DPNP) in hospitalized
      patients with diabetes mellitus (DM) type 2; b) determine the frequency of DPNP
      in hospitalized patients with type 2 DM in relation to gender, duration of
      diabetes, fasting blood glucose and HbA1c; c) identify the dominant DPNP symptoms
      and the presence of variable risk factors in hospitalized patients; and d)
      determine the frequency and motor nerve conduction velocity of n. peroneus
      (electroneuromyography) in relation to the treatment of type 2 DM in hospitalized
      patients with DPNP. MATERIAL AND METHODS: The study was conducted on 141 patients
      diagnosed with type 2 diabetes who were hospitalized at the Neurological clinic
      of Clinical Center of Sarajevo University in the period from June 1 2009 to June
      1 2010. All patients included in the study were older than 18. Values determined
      for all subjects are: age, sex, dominant symptoms, duration of type 2 DM, fasting
      blood glucose, HbA1c, motor conduction velocity of n. peroneus, diabetes risk
      factors (hyperlipidemia, hypertension, smoking, alcoholism, obesity) and DM
      treatment type. RESULTS: Of 141 patients with type 2 DM, DPNP was confirmed in 50
      patients (35.5%). Men were slightly more represented in the total sample (51.8%).
      In a sample of patients with DPNP, there were slightly more male patients (n=26;
      52%). The average age of patients with DPNP was higher in men (58.3+/-12.5)
      (p<0.05). The average age of the patients with DPNP was 55.1+/- 13.2. Average
      values of fasting glucose was higher in the group of patients with DPNP (11.032+/
      5.4 mmol/l) compared to patients without DPNP (9.7+/-2.8 mmol/l) (p<0.05). Mean
      values of HbA1C were higher in patients with DPNP (8.212+/-3.3%) compared to
      patients without DPNP (6.9+/-2.6%) (p<0.05). Analysis of DM duration between
      patients with and without DPNP did not show statistically significant difference
      (chi-square=3.858, p>0.05). In both groups, most of the patients had duration of
      DM over 10 years, with a minimum duration of DM of 12 months. There are
      statistically significant differences in applied DM therapy by gender (chi
      square=11.939, p<0.05). Hypertension was more frequent in women (79.2%:69.2%),
      hyperlipidemia was equally presented in both sexes (50%:50%), obesity was more
      prevalent among women (25%:7.7%), while alcoholism and smoking were more frequent
      in men (7.7%:0%; 34.6%:8.3%). There are statistically significant differences in
      the prevalence of risk factors by gender (chi-square=10.013, p<0.05).
      CONCLUSIONS: The DPNP incidence was higher in patients with longer duration of
      the disease, but without significant gender differences. Fasting blood glucose
      and HbA1c were significantly higher in patients with DPNP compared to patients
      without DPNP (p<0.05). The dominant symptoms of DPNP were paresthesia (44%) and
      hypoesthesia (28%). Regarding variable risk factors, the most common were
      hypertension and hyperlipidemia, without statistical significance in gender
      distribution, while smoking was significantly more common in men than women
      (34.6%:8.3%). DPNP was present in 43.2% of men who use insulin therapy, while
      54.2% of women with DPNP used oral therapy. The lowest frequency of DPNP was
      found in patients treated with combined therapy. Motor conduction velocity of n.
      peroneus was significantly lower in men using insulin therapy and/or combined
      therapy (p<0.05), whereas in patients on oral therapy there was no significant
      gender difference. Timely DM type 2 diagnosis with proper treatment and
      electromyoneurographic monitoring (especially in older men) can prevent onset of
      diabetic polyneuropathy and contribute to its successful treatment.

PMID- 24039337
TI  - Time Work by Overworked Professionals: Strategies in Response to the Stress of
      Higher Status.
AB  - How are professionals responding to the time strains brought on by the stress of
      their higher status jobs? Qualitative data from professionals reveal (a) general
      acceptance of the emerging temporal organization of professional work, including
      rising time demands and blurred boundaries around work/ nonwork times and places,
      and (b) time work as strategic responses to work intensification, overloads, and
      boundarylessness. We detected four time-work strategies: prioritizing time,
      scaling back obligations, blocking out time, and time shifting of obligations.
      These strategies are often more work-friendly than family-friendly, but "blocking
      out time" and "time shifting" suggest promising avenues for work-time policy and
      practice.

PMID- 24039338
TI  - Interpersonal Climate of 12-step Groups Predicts Reductions in Alcohol Use.
AB  - Research has shown that increases in the size of abstinence-based social networks
      helps explain the association between 12-step attendance and increased
      abstinence. This study investigated whether the quality of social interaction in
      12-step groups also predicts reduced substance use. Participants reported their
      perceptions of engagedness, avoidance, and conflict in their 12-step groups and
      their substance use in four assessments. Results showed that perceptions of group
      engagedness, but not avoidance or conflict, decreased over time. Despite this,
      engagedness predicted increased 12-step-related behavior and decreased alcohol
      use. Findings suggest that positive group interaction plays an important role in
      12-step affiliates' recovery efforts.

PMID- 24039340
TI  - When Singular and Plural are Both Grammatical: Semantic and Morphophonological
      Effects in Agreement.
AB  - The utterance planning processes allowing speakers to produce agreement between
      subjects and verbs (the catspl arepl asleep) have been the topic of extensive
      study as a window into language production mechanisms. A key question has been
      the extent to which agreement processing is influenced by semantic and
      phonological factors. Most prior studies have found limited effects of non
      syntactic, particularly phonological factors, leading to conclusions that
      agreement is computed by a process influenced strongly by syntactic factors and
      with only a minor contribution of semantics. This conclusion may have been
      influenced by use of agreement error data as the main dependent variable, because
      errors are rare, potentially reducing sensitivity to the interaction of several
      factors. Two studies investigate agreement processing in Serbian, which allows
      both singular and plural verb forms to agree with plural nouns in some
      constructions. We use these constructions to further investigate the contribution
      of semantic factors to agreement, by manipulating levels of individuation of the
      members of a set. In addition, we investigate the effect of morphophonological
      homophony onto the participants' productions of agreeing forms. The findings are
      discussed in the context of three models of agreement (Marking & Morphing,
      competition and controller misidentification), which differ in the extent to
      which they allow the influence of non-syntactic factors on agreement. We also
      compare the behavioral findings with the predictions of four computational
      implementations of the Marking & Morphing account. We discuss the implications of
      the behavioral and computational findings for models of agreement and the
      language production more broadly. Rosemary:Some biscuits or a piece of cake...
      'goes' or 'go' better with an afternoon tea?

PMID- 24039339
TI  - Conscious intention to speak proactively facilitates lexical access during overt
      object naming.
AB  - The present study explored when and how the top-down intention to speak
      influences the language production process. We did so by comparing the brain's
      electrical response for a variable known to affect lexical access, namely word
      frequency, during overt object naming and non-verbal object categorization. We
      found that during naming, the event-related brain potentials elicited for objects
      with low frequency names started to diverge from those with high frequency names
      as early as 152 ms after stimulus onset, while during non-verbal categorization
      the same frequency comparison appeared 200 ms later eliciting a qualitatively
      different brain response. Thus, only when participants had the conscious
      intention to name an object the brain rapidly engaged in lexical access. The data
      offer evidence that top-down intention to speak proactively facilitates the
      activation of words related to perceived objects.

PMID- 24039341
TI  - Comparison of Parent versus Child-Report of Child Impulsivity Traits and
      Prediction of Outcome Variables.
AB  - Five personality traits that dispose individuals to rash or ill-advised action
      (i.e., sensation seeking, negative urgency, positive urgency, lack of planning,
      and lack of perseverance), can be reliably and validly assessed in children. This
      paper reports on the first test of parental reports of these traits. In a sample
      of 94 children (ages 7-13, mean age 10.6), the authors found the following.
      First, parental reports of the five traits in their children appeared to be
      reliable. Second, there was moderate convergent validity: parent and child
      reports of the same traits had a median correlation of r = .30. Third, there was
      adequate discriminant validity: within-parent reports on different traits had a
      median correlation of r = .11. Fourth, concurrent prediction of child behavior
      from parental reports generally was inconsistent with prior findings. Fifth,
      discrepancies between the two reporters did predict dysfunctional child behavior.
      There are advantages to securing both child self-report and parental report of
      personality dispositions to rash action, although there is limited evidence for
      the concurrent validity of parental reports.

PMID- 24039342
TI  - The Cross-Cultural Association Between Marital Status and Physical Aggression
      Between Intimate Partners.
AB  - Some research suggests that the risk of physical aggression by an intimate
      partner is related to marital status, but this relationship may vary across
      cultures and by gender. In the present study, we systematically examine the
      relationship between marital status and physical partner aggression by gender
      across 19 countries. Logistic and multilevel regression confirmed previous
      findings of lower rates of physical aggression for legally married versus
      cohabiting and separated/divorced women and men across most, but notably, not all
      countries. Single status was associated with higher risk in some countries and
      lower in others reflecting possible cultural differences in risk for different
      marital statuses. For example, single women had significantly lower rates of
      victimization than did married women in India where violence against wives is
      often accepted. The variation in the cross-cultural findings highlights the
      importance of examining both men and women and considering the cultural context
      when interpreting the relationship between partner aggression and marital status.

PMID- 24039343
TI  - Intimate Relationship Aggression in College Couples: Family-of-Origin Violence,
      Egalitarian Attitude, Attachment Security.
AB  - Dating violence among college aged couples has become a growing concern with
      increasing prevalence. The current study investigated the interplay among
      witnessing violence during childhood (both parental conflict and parent to child
      aggression), attachment insecurity, egalitarian attitude within the relationship,
      and dating aggression. Participants of this study included 87 couples. Results
      from the structural equation model indicated that the proposed model provided a
      good fit to the with a chi2 to df ratio of 1.84. In particular, both female and
      male participants who reported higher levels of attachment insecurity were more
      likely to be victim of dating aggression in their relationships. Furthermore,
      female participants who reported having witnessed parental conflict were more
      likely to be victimized by their partners. In conclusion, this study provides a
      comprehensive understanding of intimate relationship violence with dyadic data
      showing, for both genders, attachment insecurity is a crucial factor in both
      victimization and perpetration of aggression.

PMID- 24039344
TI  - The role of subcortical structures in recited speech: Studies in Parkinson's
      disease.
AB  - The role of subcortical structures in language function is complex and dependent
      on language task, with studies increasingly showing subcortical involvement for
      the production of formulaic language, including recited speech. Individuals with
      Parkinson's disease (PD), with (n = 6) and without (n = 7) surgical treatment,
      deep brain stimulation (DBS), were compared to healthy adults (n = 14) to
      determine whether individuals with subcortical dysfunction produce more errors
      during a recitation speech task. Participants were asked to recite poems,
      prayers, and rhymes familiar to them in order to determine the effects of
      subcortical disease on recited speech ability. When compared with healthy
      controls, the DBS-OFF group produced significantly more error words, suggesting
      that deficits in recitation arise with severe states of subcortical dysfunction.
      Individuals with DBS in the ON or OFF conditions did not differ significantly
      during the recited speech task. Results support a model of language where large
      units of overlearned language are at least partially modulated by subcortical
      structures.

PMID- 24039346
TI  - Treatment of vitiligo with autologous cultured keratinocytes in 27 cases.
AB  - BACKGROUND: Vitiligo is an acquired depigmentation of the skin characterized by
      white spots with well-defined margins, causing psychological stress in patients
      due to cosmetic concerns. We examined 27 patients who underwent vitiligo
      treatment using autologous cultured keratinocytes. METHODS: The study comprised
      20 patients with segmental vitiligo and seven patients with generalized vitiligo,
      and they were followed up for at least 1 year postoperatively. In all 27 cases,
      topical steroid or ultraviolet therapy had been previously performed by
      dermatologists, but this treatment had been ineffective. The patients' vitiligo
      had stabilized. The patients were treated using keratinocytes obtained from
      primary culture using Green's techniques or from first passage. Dispase treatment
      was used to detach the stratified cultured epithelial sheets from their culture
      dishes. The detached sheets shrank to approximately one half to two thirds of
      their original size on the culture dish. After the recipient site was completely
      epithelialized, the skin was exposed to sunlight. RESULTS: For patients with
      segmental vitiligo, 12 had a good therapeutic outcome (90 % or more
      repigmentation) after the first surgery. This number increased to 14 when
      patients with multiple surgeries were included. There were six patients with fair
      outcomes (50-90 % repigmentation), and no patients with poor outcomes (50 % or
      less repigmentation). For patients with generalized vitiligo, no patients had a
      good outcome despite multiple surgeries. There were three patients with fair
      outcomes, and four patients with no change outcomes. CONCLUSIONS: Cultured
      keratinocyte grafting was a more effective treatment for segmental vitiligo than
      for generalized vitiligo. Level of Evidence: Level IV, therapeutic study.

PMID- 24039345
TI  - Capillary Array Waveguide Amplified Fluorescence Detector for mHealth.
AB  - Mobile Health (mHealth) analytical technologies are potentially useful for
      carrying out modern medical diagnostics in resource-poor settings. Effective
      mHealth devices for underserved populations need to be simple, low cost, and
      portable. Although cell phone cameras have been used for biodetection, their
      sensitivity is a limiting factor because currently it is too low to be effective
      for many mHealth applications, which depend on detection of weak fluorescent
      signals. To improve the sensitivity of portable phones, a capillary tube array
      was developed to amplify fluorescence signals using their waveguide properties.
      An array configured with 36 capillary tubes was demonstrated to have a ~100X
      increase in sensitivity, lowering the limit of detection (LOD) of mobile phones
      from 1000 nM to 10 nM for fluorescein. To confirm that the amplification was due
      to waveguide behavior, we coated the external surfaces of the capillaries with
      silver. The silver coating interfered with the waveguide behavior and diminished
      the fluorescence signal, thereby proving that the waveguide behavior was the main
      mechanism for enhancing optical sensitivity. The optical configuration described
      here is novel in several ways. First, the use of capillaries waveguide properties
      to improve detection of weak florescence signal is new. Second we describe here a
      three dimensional illumination system, while conventional angular laser waveguide
      illumination is spot (or line), which is functionally one-dimensional
      illumination, can illuminate only a single capillary or a single column (when a
      line generator is used) of capillaries and thus inherently limits the
      multiplexing capability of detection. The planar illumination demonstrated in
      this work enables illumination of a two dimensional capillary array (e.g. x
      columns and y rows of capillaries). In addition, the waveguide light propagation
      via the capillary wall provides a third dimension for illumination along the axis
      of the capillaries. Such an array can potentially be used for sensitive analysis
      of multiple fluorescent detection assays simultaneously. The simple phone based
      capillary array approach presented in this paper is capable of amplifying weak
      fluorescent signals thereby improving the sensitivity of optical detectors based
      on mobile phones. This may allow sensitive biological assays to be measured with
      low sensitivity detectors and may make mHealth practical for many diagnostics
      applications, especially in resource-poor and global health settings.

PMID- 24039347
TI  - Dual channel detection of ultra low concentration of bacteria in real time by
      scanning FCS.
AB  - We describe a novel method to detect very low concentrations of bacteria in
      water. Our device consists of a portable horizontal geometry small confocal
      microscope with large pinhole and a holder for cylindrical cuvettes containing
      the sample. Two motors provide a fast rotational and slow vertical motion of the
      cuvette so the device looks like a simplified flow cytometer without flow. To
      achieve high sensitivity the design has two detection channels. Bacteria are
      stained by two different nucleic acid dyes and excited with two different lasers.
      Data are analyzed with a correlation filter based on particle passage pattern
      recognition. The passage of a particle through the illumination volume is
      compared with a Gaussian pattern in both channels. The width of the Gaussian
      correlates with the time of passage of the particle so one particle is counted
      when the algorithm finds a match with a Gaussian in both channels. The
      concentration of particles in the sample is deduced from the total number of
      coincident hits and the total volume scanned. This portable setup provides higher
      sensitivity, low cost and it could have a wide use ranging from clinical
      applications to pollution monitors and water and air quality control.

PMID- 24039348
TI  - Phosphorylation and Acetylation of Acyl-CoA Synthetase- I.
AB  - Long chain acyl-CoA synthetase 1 (ACSL1) contributes 50 to 90% of total ACSL
      activity in liver, adipose tissue, and heart and appears to direct the use of
      long chain fatty acids for energy. Although the functional importance of ACSL1 is
      becoming clear, little is understood about its post-translational regulation. In
      order to investigate the post-translational modifications of ACSL1 under
      different physiological conditions, we overexpressed ACSL1 in hepatocytes, brown
      adipocytes, and 3T3-L1 differentiated adipocytes, treated these cells with
      different hormones, and analyzed the resulting phosphorylated and acetylated
      amino acids by mass spectrometry. We then compared these results to the post
      translational modifications observed in vivo in liver and brown adipose tissue
      after mice were fasted or exposed to a cold environment. We identified universal
      N-terminal acetylation, 15 acetylated lysines, and 25 phosphorylation sites on
      ACSL1. Several unique acetylation and phosphorylation sites occurred under
      conditions in which fatty acid beta-oxidation is normally enhanced. Thirteen of
      the acetylated lysines had not previously been identified, and none of the
      phosphorylation sites had been previously identified. Site-directed mutagenesis
      was used to introduce mutations at three potential acetylation and
      phosphorylation sites believed to be important for ACSL1 function. At the ATP/AMP
      binding site and at a highly conserved site near the C terminus, modifications of
      Ser278 or Lys676, respectively, totally inhibited ACSL1 activity. In contrast,
      mutations of Lys285 that mimicked acetylation (Lys285Ala and Lys285Gln) reduced
      ACSL activity, whereas full activity was retained by Lys285Arg, suggesting that
      acetylation of Lys285 would be likely to decrease ACSL1 activity. These results
      indicate that ACSL1 is highly modified post-translationally. Several of these
      modifications would be expected to alter enzymatic function, but others may
      affect protein stability or protein-protein interactions.

PMID- 24039349
TI  - Spatiotemporal patterns of GFAP upregulation in rat brain following acute
      intoxication with diisopropylfluorophosphate (DFP).
AB  - We previously demonstrated that the organophosphate diisopropylfluorophosphate
      (DFP) induced region-specific delayed neuronal injury in rat brain. The goal of
      this study was to examine the spatiotemporal pattern of the astroglial response
      after acute intoxication of rats with DFP. Rats were euthanized at varying times
      between 1 h to 7 days after DFP administration (9mg/kg, i.p.). The distribution
      of activated astrocytes in different brain regions was determined by
      immunostaining for glial fibrillary acidic acid (GFAP). GFAP immunoreactivity
      increased in the hippocampus, and piriform/entorhinal cortex at 1 h, peaked
      between 4-8 h then decreased from 16 to 24 h. GFAP labeling in the amygdala
      gradually increased over the 24 h period. A large increase in GFAP labeling was
      seen at 3-7 days following DFP administration in the hippocampus,
      piriform/entorhinal cortex and dorsolateral thalamus. At 3 days post-DFP
      exposure, GFAP immunoreactivity was totally absent in central areas of the
      hippocampus, piriform/entorhinal cortex and dorsolateral thalamus that contained
      numerous FluoroJade B (FJB) labeled neurons. By 7 days, GFAP expression was
      highly upregulated in all areas of each brain region. The mRNA expression of GFAP
      in hippocampus slowly increased at 24 h following DFP administration then
      dramatically increased at 3 days. This study suggests that activation of glial
      cells may contribute to the early neuropathological changes and later neuronal
      repair/plasticity following acute DFP intoxication.

PMID- 24039350
TI  - Confocal laser endomicroscopy in inflammatory bowel diseases: dream or reality?
AB  - Confocal laser endomicroscopy (CLE) is a newly introduced procedure that provide
      real-time, high-resolution imaging of the gastrointestinal mucosa during
      endoscopy, allowing the visualization of the pathology of the mucosal epithelium
      with its cellular and subcellular structures. Recently, the use of CLE was
      reported in the study of colonic mucosa in patients with inflammatory bowel
      diseases and in particular in patients affected by ulcerative colitis. CLE has
      the potential to have an important role in management of inflammatory bowel
      diseases (IBD) patients as it can be used to assess the grading of colitis and in
      detection of microscopic colitis in endoscopically silent segments. Moreover, CLE
      can be used in surveillance programs especially in high-risk patients. Finally,
      CLE has been effectively used in diagnosing a biliary dysplasia/neoplasia in
      patients with primary sclerosing cholangitis, a pathological condition frequently
      associated with IBD, with a coexisting bile duct stricture. 

PMID- 24039352
TI  - Appendectomy and Clostridium difficile colitis: relationships revealed by
      clinical observations and immunology.
AB  - Advances in understanding the interaction between the human immune system and the
      microbiome have led to an improved understanding of the function of the vermiform
      appendix as a safe-house for beneficial bacteria in the colon. These advances
      have been made despite long standing clinical observations that the appendectomy
      is a safe and effective procedure. However, more recent clinical data show that
      an appendectomy puts patients at increased risk for recurrent Clostridium
      difficile (C. difficile)-associated colitis, and probably other diseases
      associated with an altered microbiome. At the same time, appendectomy does not
      apparently put patients at risk for an initial onset of C. difficile-associated
      colitis. These clinical observations point toward the idea that the vermiform
      appendix might not effectively protect the microbiome in the face of broad
      spectrum antibiotics, the use of which precedes the initial onset of C. difficile
      associated colitis. Further, these observations point to the idea that
      historically important threats to the microbiome such as infectious
      gastrointestinal pathogens have been supplanted by other threats, particularly
      the use of broad spectrum antibiotics. 

PMID- 24039351
TI  - Epidemiology of esophageal cancer.
AB  - Esophageal cancer (EsC) is one of the least studied and deadliest cancers
      worldwide because of its extremely aggressive nature and poor survival rate. It
      ranks sixth among all cancers in mortality. In retrospective studies of EsC,
      smoking, hot tea drinking, red meat consumption, poor oral health, low intake of
      fresh fruit and vegetables, and low socioeconomic status have been associated
      with a higher risk of esophageal squamous cell carcinoma. Barrett's esophagus is
      clearly recognized as a risk factor for EsC, and dysplasia remains the only
      factor useful for identifying patients at increased risk, for the development of
      esophageal adenocarcinoma in clinical practice. Here, we investigated the
      epidemiologic patterns and causes of EsC. Using population based cancer data from
      the Surveillance, Epidemiology and End Results Program of the United States; we
      generated the most up-to-date stage distribution and 5-year relative survival by
      stage at diagnosis for 1998-2009. Special note should be given to the fact that
      esophageal cancer, mainly adenocarcinoma, is one of the very few cancers that is
      contributing to increasing death rates (20%) among males in the United States. To
      further explore the mechanism of development of EsC will hopefully decrease the
      incidence of EsC and improve outcomes. 

PMID- 24039353
TI  - MicroRNA-21 as a potential colon and rectal cancer biomarker.
AB  - Colorectal cancer (CRC) is one of the most common malignant diseases worldwide
      and the prognosis is still poor although much progress has been achieved in
      recent years. In order to reduce CRC-related deaths, many studies are aimed at
      identifying novel screening- and prognosis-related biomarkers. MicroRNAs (miRNAs)
      are a class of 18-27-nucleotide single-stranded RNA molecules that regulate gene
      expression at the post-transcriptional level. It has been demonstrated that
      miRNAs regulate a variety of physiological functions, including development, cell
      differentiation, proliferation, and apoptosis. They play important roles in
      various physiologic and developmental processes and in the initiation and
      progression of various human cancers. It has been shown that miRNAs can
      critically regulate tumor cell gene expression, and evidence suggests that they
      may function as both oncogenes and tumor suppressor genes. In CRC, miRNAs-21 is
      one of the most important miRNAs and is rapidly emerging as a novel biomarker in
      CRC, with good potential as a diagnostic and therapeutic target. In this review,
      we summarize the latest research findings of the clinicopathological relevance of
      miRNAs-21 in CRC initiation, development, and progress, highlighting its
      potential diagnostic, prognostic, and therapeutic application, as well as
      discussing future prospects. 

PMID- 24039354
TI  - Doxorubicin-eluting bead vs conventional transcatheter arterial chemoembolization
      for hepatocellular carcinoma before liver transplantation.
AB  - AIM: To assess the possible effect of two different types of preoperative
      transcatheter arterial chemoembolization (TACE) on recurrence-free survival after
      liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) and to
      analyze the effects of TACE on tumor histology. METHODS: We retrospectively
      analyzed the histological features of 130 HCC nodules in 63 native livers removed
      at transplantation. Patients who received any other type of treatment such as
      radiofrequency tumor ablation, percutaneous ethanol ablation or who were not
      treated at all were excluded. All patients in the present study were within the
      Milan Criteria at the last imaging findings before transplantation. Doxorubicin
      eluting bead TACE (DEB-TACE) was performed in 22 patients (38 nodules), and
      conventional TACE (c-TACE) in 16 (25 nodules). Patients' and tumors'
      characteristics were retrospectively reviewed. We performed a per-nodule analysis
      of the explanted livers to establish the mean percentage of necrosis of any
      nodule treated by TACE (conventional or DEB) and a per-patient analysis to
      establish the percentage of necrosis in the cumulative tumor area, including 21
      nodules not reached by TACE. Inflammatory and fibrotic changes in the tissue
      surrounding the tumor nodule were analyzed and categorized as poor/absent,
      moderate and enhanced reaction. Uni- and multivariate analysis of risk factors
      for HCC-recurrence were performed. RESULTS: The number and diameter of the
      nodules, the time spent on the waiting list and the number of treatments were
      similar in the two groups. A trend towards higher appropriate response rates
      (necrosis >= 90%) was observed in the DEB-TACE group (44.7% vs 32.0%, P =
      0.2834). The mean percentage of necrosis in the cumulative tumor area was 58.8%
      +/- 36.6% in the DEB-TACE group and 50.2% +/- 38.1% in the c-TACE group (P =
      0.4856). Fibrotic and inflammatory reactions surrounding the tumor nodule were
      markedly more common in the DEB-TACE group (P < 0.0001, for both the parameters).
      The three-year recurrence-free survival was higher in DEB-TACE-treated patients
      than in conventionally treated patients (87.4% vs 61.5%, P = 0.0493). Other
      factors affecting recurrence-free survival included viable tumor beyond Milan
      Criteria on histopathological examination, the percentage of necrosis on CTA <=
      50% and a pre-transplant serum alpha-fetoprotein level greater than 70 ng/mL. On
      multivariate analysis, the lack of treatment with DEB-TACE, high levels of alpha
      fetoprotein and viable tumor beyond Milan Criteria at histology examination were
      identified as independent predictors of tumor recurrence. CONCLUSION: DEB-TACE
      can effectively promote tumor necrosis and improves recurrence-free survival
      after LT in HCC.

PMID- 24039355
TI  - Protective effect of naringenin on acetic acid-induced ulcerative colitis in
      rats.
AB  - AIM: To evaluate the ameliorative effect of naringenin (NG) during ulcerative
      colitis (UC) in rats. METHODS: Rats were treated with three different doses (25,
      50 and 100 mg/kg per day) of NG and a single dose of mesalazine (MES, 300 mg/kg
      per day) for seven days prior to ulcerative colitis induction by 4% acetic acid
      (AA). Twenty four hours after AA rectal administration, animals were scarified
      and the colonic tissues were dissected. Colonic mucus content was estimated using
      Alcian blue dye binding technique. In colon tissues, levels of total glutathione
      sulphadryls (T-GSH), non-protein sulphadryls (NP-SH) and thiobarbituric acid
      reactive substances (TBARS) were evaluated. The activities of the antioxidant
      enzymes, catalase (CAT) and superoxide dismutase (SOD) were measured.
      Concentrations of nucleic acids (DNA and RNA) and total protein were also
      estimated in colon tissues. Colonic levels of tumor necrosis factor-alpha (TNF
      alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), prostaglandin E2
      (PGE2) and nitric oxide (NO) were estimated. In cross section of colitis tissue
      the histopathological changes were observed. RESULTS: Colonic mucus content was
      decreased in AA compared to controls (587.09 +/- 65.59 mg/kg vs 941.78 +/- 68.41
      mg/kg, P < 0.001). AA administration markedly reduced T-GSH (5.25 +/- 0.37 nmol/L
      vs 3.04 +/- 0.24 nmol/L, P < 0.01), NP-SH (3.16 +/- 0.04 nmol/L vs 2.16 +/- 0.30
      nmol/L, P < 0.01), CAT (6.77 +/- 0.40 U/mg vs 3.04 +/- 0.2 U/mg, P < 0.01) and
      SOD (3.10 +/- 0.11 U/mg vs 1.77 +/- 0.18 U/mg, P < 0.01) while TBARS, TNF-alpha,
      IL-1beta, IL-6, PGE2 and NO levels (15.09 +/- 3.84 nmol/L vs 59.90 +/- 16.34
      nmol/L, P < 0.01; 113.56 +/- 1.91 pg/mg vs 134.24 +/- 4.77 pg/mg, P < 0.01;
      209.20 +/- 36.38 pg/mg vs 422.19 +/- 31.47 pg/mg, P < 0.01; 250.83 +/- 25.09
      pg/mg vs 638.58 +/- 115.9 pg/mg, P < 0.01; 248.19 +/- 36.98 pg/mg vs 541.74 +/-
      58.34 pg/mg, P < 0.01 and 81.26 +/- 2.98 mmol/g vs 101.90 +/- 10.73 mmol/g, P <
      0.001) were increased in colon of rats with UC compared controls
      respectively.Naringenin supplementation, significantly and dose dependently
      increased the colonic mucus content. The elevated TBARS levels were significantly
      decreased (39.35 +/- 5.86 nmol/L, P < 0.05; 26.74 +/- 3.17 nmol/L, P < 0.01
      nmol/L and 17.74 +/- 2.69 nmol/L, P < 0.01) compared to AA (59.90 +/- 16.34
      nmol/L) group while the decreased levels of T-GSH and NP-SH and activities of CAT
      and SOD found increased by NG treatments in dose dependent manner. The decreased
      values of nucleic acids and total protein in AA group were also significantly (P
      < 0.01) increased in all three NG supplemented groups respectively. NG
      pretreatment inhibited the TNF-alpha levels (123.76 +/- 3.76 pg/mg, 122.62 +/-
      3.41 pg/mg and 121.51 +/- 2.61 pg/mg vs 134.24 +/- 4.78 pg/mg, P < 0.05) compared
      to AA group, respectively. Interleukins, IL-1beta and IL-6 levels were also
      decreased in NG50 + AA (314.37 +/- 16.31 pg/mg and 292.58 +/- 23.68 pg/mg, P <
      0.05) and NG100 + AA (416.72 +/- 49.62 pg/mg and 407.96 +/- 43.87 pg/mg, P <
      0.05) when compared to AA (352.46 +/- 8.58 pg/mg and 638.58 +/- 115.98 pg/mg)
      group. Similar decrease (P < 0.05) was seen in PGE2 and NO values when compared
      to AA group. The group pretreated with MES, as a reference drug, showed
      significant (P < 0.01) protection against the changes induced in colon tissue by
      AA administration respectively. CONCLUSION: In present study, NG produced
      antioxidant and anti-inflammatory effects demonstrating protective effect in
      inflammatory bowel disease.

PMID- 24039356
TI  - Quality of compounded topical 2% diltiazem hydrochloride formulations for anal
      fissure.
AB  - AIM: To investigate the quality of topical 2% diltiazem formulations
      extemporaneously compounded by retail pharmacies openly offering drug-compounding
      services. METHODS: A participating healthcare professional wrote 12 prescriptions
      for compounded 2% diltiazem cream, with 2 refills allowed per prescription. The
      12 sets of prescriptions were filled, at intervals of 1-2 wk between refills, at
      12 different independent retail pharmacies that openly offer drug-compounding
      services in a major metropolitan region. The 36 resultant preparations, provided
      as jars or tubes, were shipped, as soon as each was filled, at ambient
      temperature to the study core laboratory for high-performance liquid
      chromatography (HPLC) analysis, within 10 d of receipt. For the HPLC analysis, 8
      different samples of the topical diltiazem, each approximately 1 g in weight,
      were taken from prespecified locations within each container. To initiate the
      HPLC analysis, each sample was transferred to a 100 mL volumetric flask, to which
      methanol was added. The HPLC analysis was conducted in accordance with the
      laboratory-validated method for diltiazem in cream, ointment, and gel
      formulations. The main outcome measures were potency (percentage of label claim)
      and content uniformity of the compounded topical 2% diltiazem formulations.
      RESULTS: Of the 36 prescriptions filled, 30 were packaged in jars and 6 were
      packaged as tubes. The prescriptions were specifically for cream formulations,
      but 6 of the 12 pharmacies compounded 2% diltiazem as an ointment; for another
      pharmacy, which had inadequate labeling, the dosage form was unknown. The United
      States Pharmacopoeia (USP) standard for potency is 90%-115% of label claim. Of
      the 36 preparations, 5 (13.89%) were suprapotent and 13 (36.11%) were subpotent.
      The suprapotent prescriptions ranged in potency from 117.2% to 128.5% of label
      claim, and the subpotent prescriptions ranged in potency from 34.8% to 89.8% of
      label claim. Fourteen (38.9%) preparations lacked content uniformity according to
      the USP standard of 90%-110% potency and < 6% relative standard deviation. Of the
      30 formulations packaged in jars, 12 (40%) lacked content uniformity, while of
      the 6 formulations packaged in tubes, 2 (33.3%) lacked content uniformity. Nine
      of the 12 pharmacies (75%) failed USP potency or content-uniformity
      specifications for at least 1 of the 3 prescription fills. For 5 of the 12
      pharmacies (41.7%), the mean potency across all three prescription fills was <
      90% of label claim. CONCLUSION: Patients prescribed topical 2% diltiazem for
      treatment of anal fissure frequently receive compounded formulations that are
      misbranded with respect to potency and that lack content uniformity.

PMID- 24039357
TI  - Colorectal cancer in patients under 50 years of age: a retrospective analysis of
      two institutions' experience.
AB  - AIM: To investigate the epidemiological characteristics of colorectal cancer
      (CRC) in patients under 50 years of age across two institutions. METHODS: Records
      of patients under age 50 years of age who had CRC surgery over a 16 year period
      were assessed at two institutions. The following documents where reviewed:
      admission notes, operative notes, and discharge summaries. The main study
      variables included: age, presenting symptoms, family history, tumor location,
      operation, stage/differentiation of disease, and post operative complications.
      Stage of disease was classified according to the American Joint Committee on
      Cancer TNM staging system: tumor depth; node status; and metastases. RESULTS: CRC
      was found in 180 patients under age 50 years (87 females, 93 males; mean age 41.4
      +/- 6.2 years). Young patients accounted for 11.2% of cases during a 6 year
      period for which the full data set was available. Eight percent had a 1(st)
      degree and 12% a 2(nd) degree family CRC history. Almost all patients (94%) were
      symptomatic at diagnosis; common symptoms included: bleeding (59%), obstruction
      (9%), and abdominal/rectal pain (35%). Evaluation was often delayed and bleeding
      frequently attributed to hemorrhoids. Advanced stage CRC (Stage 3 or 4) was noted
      in 53% of patients. Most tumors were distal to the splenic flexure (77%) and 39%
      involved the rectum. Most patients (95%) had segmental resections; 6 patients had
      subtotal/total colectomy. Poorly differentiated tumors were noted in 12% and
      mucinous lesions in 19% of patients of which most had Stage 3 or 4 disease.
      Twenty-two patients (13%) developed recurrence and/or progression of disease to
      date. Three patients (ages 42, 42 and 49 years) went on to develop metachronous
      primary colon cancers within 3 to 4 years of their initial resection. CONCLUSION:
      CRC was common in young patients with no family history. Young patients with
      symptoms merit a timely evaluation to avoid presentation with late stage CRC.

PMID- 24039358
TI  - Cardiovascular disease risk factor profiles in children with celiac disease on
      gluten-free diets.
AB  - AIM: To describe the cardiovascular disease (CVD) risk factors in a population of
      children with celiac disease (CD) on a gluten-free diet (GFD). METHODS: This
      cross-sectional multicenter study was performed at Schneider Children's Medical
      Center of Israel (Petach Tiqva, Israel), and San Paolo Hospital (Milan, Italy).
      We enrolled 114 CD children in serologic remission, who were on a GFD for at
      least one year. At enrollment, anthropometric measurements, blood lipids and
      glucose were assessed, and compared to values at diagnosis. The homeostasis model
      assessment-estimated insulin resistance was calculated as a measure of insulin
      resistance. RESULTS: Three or more concomitant CVD risk factors [body mass index,
      waist circumference, low density lipoprotein (LDL) cholesterol, triglycerides,
      blood pressure and insulin resistance] were identified in 14% of CD subjects on a
      GFD. The most common CVD risk factors were high fasting triglycerides (34.8%),
      elevated blood pressure (29.4%), and high concentrations of calculated LDL
      cholesterol (24.1%). On a GFD, four children (3.5%) had insulin resistance.
      Fasting insulin and HOMA-IR were significantly higher in the Italian cohort
      compared to the Israeli cohort (P < 0.001). Children on a GFD had an increased
      prevalence of borderline LDL cholesterol (24%) when compared to values (10%) at
      diagnosis (P = 0.090). Trends towards increases in overweight (from 8.8% to
      11.5%) and obesity (from 5.3% to 8.8%) were seen on a GFD. CONCLUSION: This
      report of insulin resistance and CVD risk factors in celiac children highlights
      the importance of CVD screening, and the need for dietary counseling targeting
      CVD prevention.

PMID- 24039359
TI  - 5-ASA colonic mucosal concentrations resulting from different pharmaceutical
      formulations in ulcerative colitis.
AB  - AIM: To compare the mucosal concentrations of 5-aminosalicylic acid (5-ASA)
      resulting from different pharmaceutical formulations and analyse the influence of
      inflammation on the mucosal concentrations. METHODS: The study included 130
      inflammatory bowel disease (IBD) patients receiving 5-ASA as pH-dependent-release
      formulations (73 patients), time-dependent-release formulations (11 patients), or
      pro-drugs (18 patients). In addition, 28 patients were receiving topical
      treatment (2-4 g/d) with pH-dependent-release formulations. Endoscopic biopsies
      were obtained from the sigmoid region during the colonoscopy. The 5-ASA
      concentrations (ng/mg) were measured in tissue homogenates using high-pressure
      liquid chromatography with electrochemical detection. The t test and Mann-Whitney
      test, when appropriate, were used for statistical analysis. RESULTS: Patients
      receiving pH-dependent-release formulations showed significantly higher mucosal
      concentrations of 5-ASA (51.75 +/- 5.72 ng/mg) compared with patients receiving
      pro-drugs (33.35 +/- 5.78 ng/mg, P = 0.01) or time-dependent-release formulations
      (38.24 +/- 5.53 ng/mg, P = 0.04). Patients with endoscopic remission had
      significantly higher mucosal concentrations of 5-ASA than patients with active
      disease (60.14 +/- 7.95 ng/mg vs 35.66 +/- 5.68 ng/mg, P = 0.02). Similar results
      were obtained when we compared patients with the histological appearance of
      remission and patients with active histological inflammation (67.53 +/- 9.22
      ng/mg vs 35.53 +/- 5.63 ng/mg, P < 0.001). Significantly higher mucosal
      concentrations of 5-ASA were detected in patients treated with both oral and
      topical treatments in combination compared with patients who received oral
      treatment with pH-dependent-release formulations alone (72.33 +/- 11.23 ng/mg vs
      51.75 +/- 5.72 ng/mg, P = 0.03). CONCLUSION: IBD patients showed significant
      variability in mucosal 5-ASA concentrations depending on the type of formulation,
      and the highest mean concentration was achieved using pH-dependent-release
      formulations.

PMID- 24039360
TI  - Eviendep(r) reduces number and size of duodenal polyps in familial adenomatous
      polyposis patients with ileal pouch-anal anastomosis.
AB  - AIM: To evaluate if 3 mo oral supplementation with Eviendep(r) was able to reduce
      the number of duodenal polyps in familial adenomatous polyposis (FAP) patients
      with ileal pouch-anal anastomosis (IPAA). METHODS: Eleven FAP patients with IPAA
      and duodenal polyps were enrolled. They underwent upper gastrointestinal (GI)
      endoscopy at the baseline and after 3 mo of treatment. Each patient received 5 mg
      Eviendep twice a day, at breakfast and dinner time, for 3 mo. Two endoscopists
      evaluated in a blinded manner the number and size of duodenal polyps. Upper GI
      endoscopies with biopsies were performed at the baseline (T0) with the assessment
      of the Spigelman score. Polyps > 10 mm were removed during endoscopy and at the
      end of the procedure a new Spigelman score was determined (T1). The procedure was
      repeated 3 mo after the baseline (T2). Four photograms were examined for each
      patient, at T1 and T2. The examined area was divided into 3 segments: duodenal
      bulb, second and third portion duodenum. Biopsy specimens were taken from all
      polyps > 10 mm and from all suspicious ones, defined by the presence of a central
      depression, irregular surface, or irregular vascular pattern. Histology was
      classified according to the updated Vienna criteria. RESULTS: At baseline the
      mean number of duodenal detected polyps was 27.7 and mean sizes were 15.8 mm; the
      mean Spigelman score was 7.1. After polypectomy the mean number of duodenal
      detected polyps was 25.7 and mean sizes were 7.6 mm; the mean Spigelman score was
      6.4. After 3 mo of Eviendep bid, all patients showed a reduction of number and
      size of duodenal polyps. The mean number of duodenal polyps was 8 (P = 0.021) and
      mean size was 4.4 mm; the mean Spigelman score was 6.6. Interrater agreement was
      measured. Lesions > 1 cm found a very good degree of concordance (kappa 0.851)
      and a good concordance was as well encountered for smaller lesions (kappa 0.641).
      CONCLUSION: Our study demonstrated that short-term (90 d) supplementation with
      Eviendep(r) in FAP patients with IPAA and with recurrent adenomas in the duodenal
      mucosa, resulted effective in reducing polyps number of 32% and size of 51%.

PMID- 24039361
TI  - Fatty acids of erythrocyte membrane in acute pancreatitis patients.
AB  - AIM: To evaluate changes in the fatty acid composition of erythrocyte membrane
      phospholipids during severe and mild acute pancreatitis (AP) of alcoholic and
      nonalcoholic etiology. METHODS: All consecutive patients with a diagnosis of AP
      and onset of the disease within the last 72 h admitted to the Hospital of
      Lithuanian University of Health Sciences between June and December 2007 were
      included. According to the Acute Physiology and Chronic Health Evaluation (APACHE
      II) scale, the patients were subdivided into the mild (APACHE II score < 7, n =
      22) and severe (APACHE II score >= 7, n = 17) AP groups. Healthy individuals (n =
      26) were enrolled as controls. Blood samples were collected from patients on
      admission to the hospital. Fatty acids (FAs) were extracted from erythrocyte
      phospholipids and expressed as percentages of the total FAs present in the
      chromatogram. The concentrations of superoxide dismutase and glutathione
      peroxidase were measured in erythrocytes. RESULTS: We found an increase in the
      percentages of saturated and monounsaturated FAs, a decrease in the percentages
      of total polyunsaturated FAs (PUFAs) and n-3 PUFAs in erythrocyte membrane
      phospholipids of AP patients compared with healthy controls. Palmitic (C16:0),
      palmitoleic (C16:1n7cis), arachidonic (C20:4n6), docosahexaenoic (DHA, C22:6n3),
      and docosapentaenoic (DPA, C22:5n3) acids were the major contributing factors. A
      decrease in the peroxidation and unsaturation indexes in AP patients as well as
      the severe and mild AP groups as compared with controls was observed. The
      concentrations of antioxidant enzymes in the mild AP group were lower than in the
      control group. In severe AP of nonalcoholic etiology, the percentages of
      arachidic (C20:0) and arachidonic (C20:4n6) acids were decreased as compared with
      the control group. The patients with mild AP of nonalcoholic etiology had the
      increased percentages of total saturated FAs and gama linoleic acid (C18:3n6) and
      the decreased percentages of elaidic (C18:1n9t), eicosapentaenoic acid (EPA,
      C20:5n3), DPA (C22:5n3), DHA (C22:6n3) as well as total and n-3 PUFAs in
      erythrocyte membrane phospholipids. CONCLUSION: The composition of FAs in
      erythrocyte membranes is altered during AP. These changes are likely to be
      associated with alcohol consumption, inflammatory processes, and oxidative
      stress.

PMID- 24039362
TI  - Diversity of Helicobacter pylori genotypes in Iranian patients with different
      gastroduodenal disorders.
AB  - AIM: To investigate the diversity of Helicobacter pylori (H. pylori) genotypes
      and correlations with disease outcomes in an Iranian population with different
      gastroduodenal disorders. METHODS: Isolates of H. pylori from patients with
      different gastroduodenal disorders were analyzed after culture and identification
      by phenotypic and genotypic methods. Genomic DNA was extracted with the QIAamp
      DNA mini kit (Qiagen, Germany). After DNA extraction, genotyping was done for
      cagA, vacA (s and m regions), iceA (iceA1 , iceA2 ) and babA with specific
      primers for each allele using polymerase chain reaction (PCR). All patients'
      pathologic and clinical data and their relation with known genotypes were
      analyzed by using SPSS version 19.0 software. chi2 test and Fisher's exact test
      were used to assess relationships between categorical variables. The level of
      statistical significance was set at P < 0.05. RESULTS: A total of 71 isolates
      from 177 patients with different gastroduodenal disorders were obtained. Based on
      analysis of the cagA gene (positive or negative), vacA s-region (s1 or s2), vacA
      m-region (m1 or m2), iceA allelic type (iceA1 and iceA2 ) and babA gene (positive
      or negative), twenty different genotypic combinations were recognized. The
      prevalence of cagA, vacA s1 , vacA s2 , vacA m1 , vacA m2 , iceA1 , iceA2 ,
      iceA1+iceA2 and babA were 62%, 78.9%, 19.7%, 21.1%, 78.9%, 15.5%, 22.5%, 40.8%
      and 95.8%, respectively. Interestingly, evaluation of PCR results for cagA in 6
      patients showed simultaneous existence of cagA variants according to their size
      diversities that proposed mixed infection in these patients. The most prevalent
      genotype in cagA-positive isolates was cagA+/vacAs1m2 /iceA1 +A2 /babA+ and in
      cagA-negative isolates was cagA-/vacAs1m2 /iceA-/babA+. There were no
      relationships between the studied genes and histopathological findings (H. pylori
      density, neutrophil activity, lymphoid aggregation in lamina propria and
      glandular atrophy). The strains which carry cagA, vacAs1/m1 , iceA2 and babA
      genes showed significant associations with severe active chronic gastritis (P =
      0.011, 0.025, 0.020 and 0.031, respectively). The vacAs1 genotype had significant
      correlation with the presence of the cagA gene (P = 0.013). Also, babA genotype
      showed associations with cagA (P = 0.024). In the combined genotypes, only
      cagA+/vacAs1m1 /iceA2 /babA+ genotype showed correlation with severe active
      chronic gastritis (P = 0.025). CONCLUSION: This genotyping panel can be a useful
      tool for detection of virulent H. pylori isolates and can provide valuable
      guidance for prediction of the clinical outcomes.

PMID- 24039363
TI  - Polymorphism in the interleukin-17A promoter contributes to gastric cancer.
AB  - AIM: To evaluate the contribution of the G-197A polymorphism in the interleukin
      17 (IL-17) promoter region to gastric cancer risk in an Iranian population.
      METHODS: We performed a case control study using samples from 161 individuals
      with gastric cancer and 171 healthy controls. For each individual, the G-197A
      genotype was determined by restriction fragment length polymorphism analysis of
      polymerase chain reaction-amplified fragments. Statistical analyses were
      performed to determine whether any demographic or behavioral factors, infection
      with Helicobacter pylori (H. pylori), or a particular G-197A genotype was
      associated with gastric cancer risk. RESULTS: We found that the G-197A genotype
      was significantly associated with increased gastric cancer risk (P = 0.001).
      Patients who were homozygous (AA) at position -197 were 2.9 times more likely to
      develop disease (95%CI: 1.56-5.4; P = 0.001). Furthermore, logistic regression
      analysis revealed that the presence of a single A allele increased the risk of
      gastric cancer up to 1.7-fold (95%CI: 1.26-2.369; P = 0.001). This association
      was observed for early stage gastric adenocarcinomas only, and was not linked to
      H. pylori infection. CONCLUSION: These results suggest that carrying one or more
      G-197A polymorphisms at position -197 in the IL-17 promoter region significantly
      increases gastric cancer risk in this patient population.

PMID- 24039364
TI  - Chronological changes in the liver after temporary partial portal venous
      occlusion.
AB  - AIM: To investigate time-dependent changes caused by temporal portal vein
      obstruction and subsequent reperfusion in the lobe with or without an occluded
      portal vein. METHODS: The portal vein (PV) of the anterior lobe of the liver of a
      male Wistar rat (8 wk-old) was obstructed (70%) for 12, 24, 36 and 48 h,
      respectively, and models were sacrificed at 48 h after reperfusion (each group: n
      = 10). The histological changes and the status of liver regeneration were
      compared between a liver biopsy performed on each lobe after temporary
      obstruction of the portal vein in the same rat liver, and the liver extracted at
      the time of sacrifice (48 h after reperfusion). RESULTS: With regard to the
      obstructed lobe, the liver weight/body weight ratio significantly decreased
      according to obstruction time. On the other hand, in the non-obstructed lobe,
      there were no significant differences within each group. The duration of PV
      occlusion did not seem to be strong enough to introduce liver weight increase.
      Stimulation of liver regeneration was brought about in the non-occluded lobe by
      12-h occlusion, and was sustained even at 48 h after reperfusion. The obstructed
      lobe atrophied with the passage of time in the obstructed state. However, the
      proliferating-cell nuclear antigen labeling index also increased at 48 h after
      reperfusion, and a repair mechanism was observed. CONCLUSION: Temporary blood
      flow obstruction of the portal vein may become a significant trigger for liver
      regeneration, even with an obstruction of 12 h.

PMID- 24039365
TI  - Efficacy of treatment with rebamipide for endoscopic submucosal dissection
      induced ulcers.
AB  - AIM: To prospectively compare the healing rates of endoscopic submucosal
      dissection (ESD)-induced ulcers treated with either a proton-pump inhibitor (PPI)
      or rebamipide. METHODS: We examined 90 patients with early gastric cancer who had
      undergone ESD. All patients were administered an intravenous infusion of the PPI
      lansoprazole (20 mg) every 12 h for 2 d, followed by oral administration of
      lansoprazole (30 mg/d, 5 d). After 7-d treatment, the patients were randomly
      assigned to 2 groups and received either lansoprazole (30 mg/d orally, n = 45;
      PPI group) or rebamipide (300 mg orally, three times a day; n = 45; rebamipide
      group). At 4 and 8 wk after ESD, the ulcer outcomes in the 2 groups were
      compared. RESULTS: No significant differences were noted in patient age,
      underlying disease, tumor location, Helicobacter pylori infection rate, or ESD
      induced ulcer size between the 2 groups. At both 4 and 8 wk, the healing rates of
      ESD-induced ulcers were similar in the PPI-treated and the rebamipide-treated
      patients (4 wk: PPI, 27.2%; rebamipide, 33.3%; P = 0.5341; 8 wk: PPI, 90.9%;
      rebamipide, 93.3%; P = 0.6710). At 8 wk, the rates of granulation lesions
      following ulcer healing were significantly higher in the PPI-treated group
      (13.6%) than in the rebamipide-treated group (0.0%; P = 0.0103). Ulcer-related
      symptoms were similar in the 2 treatment groups at 8 wk. The medication cost of 8
      wk treatment with the PPI was 10945 yen vs 4889 yen for rebamipide. No ulcer
      bleeding or complications due to the drugs were observed in either treatment
      group. CONCLUSION: The healing rate of ESD-induced ulcers was similar with
      rebamipide or PPI treatment; however, rebamipide treatment is more cost-effective
      and prevents granulation lesions following ulcer healing.

PMID- 24039366
TI  - Comparison of pancreatic acinar cell carcinoma and adenocarcinoma using
      multidetector-row computed tomography.
AB  - AIM: To distinguish acinar cell carcinoma (ACC) from pancreatic adenocarcinoma
      (AC) by comparing their computed tomography findings. METHODS: Patients with ACC
      and AC were identified on the basis of results obtained using surgically resected
      pancreatectomy specimens. The preoperative computer tomographic images of 6
      acinar cell carcinoma patients and 67 pancreatic adenocarcinoma patients in 4
      phases (non-contrast, arterial, portal venous, and delayed phase) were compared.
      The scan delay times were 40, 70, and 120 s for each contrast-enhanced phase. The
      visual pattern, tomographic attenuation value, and time attenuation curve were
      assessed and compared between AC and ACC cases using the chi2 test, Wilcoxon
      signed-rank test, and Mann Whitney U test. RESULTS: The adenocarcinomas tended to
      be hypodense in all 4 phases. The acinar cell carcinomas also tended to be
      hypodense in the 3 contrast-enhanced phases, although their computed tomographic
      attenuation values were higher. Further, 5 of the 6 acinar cell carcinomas (83%)
      were isodense in the non-contrast phase. The time attenuation curve of the
      adenocarcinomas showed a gradual increase through the 4 phases, and all
      adenocarcinomas showed peak enhancement during the delayed phase. The time
      attenuation curve of the acinar cell carcinomas showed peak enhancement during
      the portal venous phase in 4 cases and during the arterial phase in 2 cases. None
      of the 6 acinar cell carcinomas showed peak enhancement during the delayed phase.
      CONCLUSION: The tumor density in the non-contrast phase and time attenuation
      curve pattern clearly differ between acinar cell carcinomas and adenocarcinomas,
      and multidetector-row computed tomography can thus distinguish these tumors.

PMID- 24039367
TI  - Laparoscopic-endoscopic cooperative surgery for gastric submucosal tumors.
AB  - AIM: To assess the feasibility, safety, and advantages of minimally invasive
      laparoscopic-endoscopic cooperative surgery (LECS) for gastric submucosal tumors
      (SMT). METHODS: We retrospectively analyzed 101 consecutive patients, who had
      undergone partial, proximal, or distal gastrectomy using LECS for gastric SMT at
      Peking Union Medical College Hospital from June 2006 to April 2013. All patients
      were followed up by visit or telephone. Clinical data, surgical approach,
      pathological features such as the size, location, and pathological type of each
      tumor; and follow-up results were analyzed. The feasibility, safety and
      effectiveness of LECS for gastric SMT were evaluated, especially for patients
      with tumors located near the cardia or pylorus. RESULTS: The 101 patients
      included 43 (42.6%) men and 58 (57.4%) women, with mean age of 51.2 +/- 13.1
      years (range, 14-76 years). The most common symptom was belching. Almost all (n =
      97) patients underwent surgery with preservation of the cardia and pylorus, with
      the other four patients undergoing proximal or distal gastrectomy. The mean
      distance from the lesion to the cardia or pylorus was 3.4 +/- 1.3 cm, and the
      minimum distance from the tumor edge to the cardia was 1.5 cm. Tumor pathology
      included gastrointestinal stromal tumor in 78 patients, leiomyoma in 13,
      carcinoid tumors in three, ectopic pancreas in three, lipoma in two, glomus tumor
      in one, and inflammatory pseudotumor in one. Tumor size ranged from 1 to 8.2 cm,
      with 65 (64.4%) lesions < 2 cm, 32 (31.7%) > 2 cm, and four > 5 cm. Sixty-six
      lesions (65.3%) were located in the fundus, 21 (20.8%) in the body, 10 (9.9%) in
      the antrum, three (3.0%) in the cardia, and one (1.0%) in the pylorus. During a
      median follow-up of 28 mo (range, 1-69 mo), none of these patients experienced
      recurrence or metastasis. The three patients who underwent proximal gastrectomy
      experienced symptoms of regurgitation and belching. CONCLUSION: Laparoscopic
      endoscopic cooperative surgery is feasible and safe for patients with gastric
      submucosal tumor. Endoscopic intraoperative localization and support can help
      preserve the cardia and pylorus during surgery.

PMID- 24039368
TI  - Clonal immunoglobulin heavy chain and T-cell receptor gamma gene rearrangements
      in primary gastric lymphoma.
AB  - AIM: To study the diagnostic value of immunoglobulin heavy chain (IgH) and T-cell
      receptor gamma (TCR-gamma) gene monoclonal rearrangements in primary gastric
      lymphoma (PGL). METHODS: A total of 48 patients with suspected PGL at our
      hospital were prospectively enrolled in this study from January 2009 to December
      2011. The patients were divided into three groups (a PGL group, a gastric linitis
      plastica group, and a benign gastric ulcer group) based on the pathological
      results (gastric mucosal specimens obtained by endoscopy or surgery) and follow
      up. Endoscopic ultrasonography (EUS) and EUS-guided biopsy were performed in all
      the patients. The tissue specimens were used for histopathological examination
      and for IgH and TCR-gamma gene rearrangement polymerase chain reaction analyses.
      RESULTS: EUS and EUS-guided biopsy were successfully performed in all 48
      patients. In the PGL group (n = 21), monoclonal IgH gene rearrangements were
      detected in 14 (66.7%) patients. A positive result for each set of primers was
      found in 12 (57.1%), 8 (38.1%), and 4 (19.0%) cases using FR1/JH, FR2/JH, and
      FR3/JH primers, respectively. Overall, 12 (75%) patients with mucosal-associated
      lymphoid tissue lymphoma (n = 16) and 2 (40%) patients with diffuse large B-cell
      lymphoma (n = 5) were positive for monoclonal IgH gene rearrangements. No
      patients in the gastric linitis plastica group (n = 17) and only one (10%)
      patient in the benign gastric ulcer group (n = 10) were positive for a monoclonal
      IgH gene rearrangement. No TCR-gamma gene monoclonal rearrangements were
      detected. The sensitivity of monoclonal IgH gene rearrangements was 66.7% for a
      PGL diagnosis, and the specificity was 96.4%. In the PGL group, 8 (100%) patients
      with stage IIE PGL (n = 8) and 6 (46.1%) patients with stage IE PGL (n = 13) were
      positive for monoclonal IgH gene rearrangements. CONCLUSION: IgH gene
      rearrangements may be associated with PGL staging and may be useful for the
      diagnosis of PGL and for differentiating between PGL and gastric linitis
      plastica.

PMID- 24039369
TI  - Application value of multi-slice spiral computed tomography for imaging
      determination of metastatic lymph nodes of gastric cancer.
AB  - AIM: To evaluate the application value of multi-slice spiral computed tomography
      (MSCT) for imaging determination of metastatic lymph nodes of gastric cancer and
      to explore reasonable diagnostic criteria. METHODS: Sixty patients with gastric
      cancer underwent 64 MSCT scans before operation. Gastric cancer samples and
      perigastric lymph nodes were obtained after operation, formalin fixation and
      haematoxylin-eosin staining. The metastatic conditions of gastric cancer and
      perigastric lymph nodes were determined under a light microscope. A total of 605
      lymph nodes were grouped and assessed according to distribution, size, shape and
      degree of lymph node enhancement. Then, the findings were compared with the
      postoperative pathological results. RESULTS: Among 605 lymph nodes, 358 were
      confirmed as metastatic, accounting for 59.2%. A total of 535 lymph nodes were
      detected in original axis images combined with multiplanar reconstruction images
      of MSCT. The metastatic lymph nodes had specific signs in computed tomography.
      This study showed that the long diameter of lymph nodes >= 8 mm indicated
      metastasis; the sensitivity and specificity were 79.6% and 78.8%, respectively.
      The difference of the mean value of lymph node enhancement density >= 80 Hu
      indicated metastasis; the sensitivity and specificity were 81.6% and 75.6%,
      respectively. The ratio of short diameter to long diameter of lymph nodes >= 0.7
      indicated metastasis; the sensitivity and specificity were 85.6% and 71.8%,
      respectively. CONCLUSION: MSCT is a non-invasive and reliable method for
      preoperative examination of gastric cancer. Sensitivity and specificity for
      prediction of lymph node metastasis are high.

PMID- 24039370
TI  - Induction of clinical response and remission of inflammatory bowel disease by use
      of herbal medicines: a meta-analysis.
AB  - AIM: To evaluate the efficacy and tolerability of herbal medicines in
      inflammatory bowel disease (IBD) by conducting a meta-analysis. METHODS:
      Electronic databases were searched for studies investigating efficacy and/or
      tolerability of herbal medicines in the management of different types of IBD. The
      search terms were: "herb" or "plant" or "herbal" and "inflammatory bowel
      disease". Data were collected from 1966 to 2013 (up to Feb). The "clinical
      response", "clinical remission", "endoscopic response", "endoscopic remission",
      "histological response", "histological remission", "relapse", "any adverse
      events", and "serious adverse events" were the key outcomes of interest. We used
      the Mantel-Haenszel, Rothman-Boice method for fixed effects and DerSimonian-Laird
      method for random-effects. For subgroup analyses, we separated the studies by
      type of IBD and type of herbal medicine to determine confounding factors and
      reliability. RESULTS: Seven placebo controlled clinical trials met our criteria
      and were included (474 patients). Comparison of herbal medicine with placebo
      yielded a significant RR of 2.07 (95%CI: 1.41-3.03, P = 0.0002) for clinical
      remission; a significant RR of 2.59 (95%CI: 1.24-5.42, P = 0.01) for clinical
      response; a non-significant RR of 1.33 (95%CI: 0.93-1.9, P = 0.12) for endoscopic
      remission; a non-significant RR of 1.69 (95%CI: 0.69-5.04) for endoscopic
      response; a non-significant RR of 0.64 (95%CI: 0.25-1.81) for histological
      remission; a non-significant RR of 0.86 (95%CI: 0.55-1.55) for histological
      response; a non-significant RR of 0.95 (95%CI: 0.52-1.73) for relapse; a non
      significant RR of 0.89 (95%CI: 0.75-1.06, P = 0.2) for any adverse events; and a
      non-significant RR of 0.97 (95%CI: 0.37-2.56, P = 0.96) for serious adverse
      events. CONCLUSION: The results showed that herbal medicines may safely induce
      clinical response and remission in patients with IBD without significant effects
      on endoscopic and histological outcomes, but the number of studies is limited to
      make a strong conclusion.

PMID- 24039371
TI  - Pancreatic paracoccidioidomycosis simulating malignant neoplasia: case report.
AB  - Paracoccidioidomycosis is a systemic granulomatous disease caused by fungus, and
      must be considered in the differential diagnosis of intra-abdominal tumors in
      endemic areas. We report a rare case of paracoccidioidomycosis in the pancreas. A
      45-year-old man was referred to our institution with a 2-mo history of epigastric
      abdominal pain that was not diet-related, with night sweating, inappetence,
      weight loss, jaundice, pruritus, choluria, and acholic feces, without signs of
      sepsis or palpable tumors. Abdominal ultrasonography (US) showed a solid mass of
      approximately 7 cm * 5.5 cm on the pancreas head. Abdominal computerized
      tomography showed dilation of the biliary tract, an enlarged pancreas (up to 4.5
      in the head region), with dilation of the major pancreatic duct. The patient
      underwent exploratory laparotomy, and the surgical description consisted of a
      tumor, measuring 7 to 8 cm with a poorly-defined margin, adhering to posterior
      planes and mesenteric vessels, showing an enlarged bile duct. External drainage
      of the biliary tract, Roux-en-Y gastroenteroanastomosis, lymph node excision, and
      biopsies were performed, but malignant neoplasia was not found. Microscopic
      analysis showed chronic pancreatitis and a granulomatous chronic inflammatory
      process in the choledochal lymph node. Acid-alcohol resistant bacillus and fungus
      screening were negative. Fine-needle aspiration of the pancreas was performed
      under US guidance. The smear was compatible with infection by Paracoccidioides
      brasiliensis. We report a rare case of paracoccidioidomycosis simulating a
      malignant neoplasia in the pancreas head. 

PMID- 24039372
TI  - Extended therapy duration for therapy-refractory hepatitis C patients with
      genotype 2.
AB  - We devised an extended 72-wk peginterferon-alpha-2a/ribavirin therapy regimen for
      the retreatment of highly intractable cases, i.e., 48-wk peginterferon-alpha
      2b/ribavirin therapy-intractable cases. Although 2 cases achieved a rapid
      virological response to 72-wk peginterferon-alpha-2a/ribavirin therapy, 1 case
      failed to achieve a sustained virological response. Although the reason for this
      difference in the effectiveness of 72-wk peginterferon-alpha-2a/ribavirin therapy
      between the cases was unclear, the rebound phenomenon of serum transaminase after
      48-wk peginterferon-alpha-2b/ribavirin therapy and the resultant lower viral load
      compared to that before 48-wk peginterferon-alpha-2b/ribavirin therapy might have
      influenced the treatment outcome. Thus, it may be beneficial to consider the
      rebound phenomenon of serum transaminase and the changes in viral load resulting
      from previous interferon-based therapy and then cautiously determine the
      indication and the timing of the administration of 72-wk peginterferon-alpha
      2a/ribavirin in highly intractable cases. Further studies should be performed to
      confirm this strategy. 

PMID- 24039373
TI  - Cerebral and splenic infarctions after injection of N-butyl-2-cyanoacrylate in
      esophageal variceal bleeding.
AB  - Variceal bleeding is the most serious complication of portal hypertension, and it
      accounts for approximately one fifth to one third of all deaths in liver
      cirrhosis patients. Currently, endoscopic treatment remains the predominant
      method for the prevention and treatment of variceal bleeding. Endoscopic
      treatments include band ligation and injection sclerotherapy. Injection
      sclerotherapy with N-butyl-2-cyanoacrylate has been successfully used to treat
      variceal bleeding. Although injection sclerotherapy with N-butyl-2-cyanoacrylate
      provides effective treatment for variceal bleeding, injection of N-butyl-2
      cyanoacrylate is associated with a variety of complications, including systemic
      embolization. Herein, we report a case of cerebral and splenic infarctions after
      the injection of N-butyl-2-cyanoacrylate to treat esophageal variceal bleeding. 

PMID- 24039374
TI  - Acute iatrogenic Budd-Chiari syndrome following hepatectomy for hepatolithiasis:
      a report of two cases.
AB  - Budd-Chiari syndrome (BCS) is defined as hepatic venous outflow obstruction at
      any level from the small hepatic veins to the junction of the inferior vena cava
      (IVC) and the right atrium, regardless of the cause of obstruction. We present
      two cases of acute iatrogenic BCS and our clinical management of these cases. The
      first case was a 43-year-old woman who developed acute BCS following the
      implantation of an IVC stent for the correction of stenosis in the IVC after
      hepatectomy for hepatolithiasis. The second case was a 61-year-old woman with
      complete obstruction of the outflow of hepatic veins during bilateral hepatectomy
      for hepatolithiasis. Acute iatrogenic BCS should be considered a rare
      complication following hepatectomy for hepatolithiasis. Awareness of potential
      hepatic outflow obstructions and timely management are critical to avoid poor
      outcomes when performing hepatectomy for hepatolithiasis. 

PMID- 24039375
TI  - Links Among Italian Preschoolers' Socio-Emotional Competence, Teacher-Child
      Relationship Quality and Peer Acceptance.
AB  - The purpose of the present study was to examine the relations of teacher-child
      relationship quality (close, conflictive, and dependent), children's social
      behavior, and peer likability in a sample of Italian preschool-aged children (46
      boys; 42 girls). Preschool teachers evaluated the quality of the teacher-child
      relationship and children's social behaviors (i.e., social competence, anger
      aggression, and anxiety-withdrawal). Peer-rated likability was measured using a
      sociometric procedure. Results indicated that conflictual teacher-child
      relationships were related to high aggressive behavior, and dependent teacher
      child relationships were positively associated with children's anxiety
      withdrawal. Moreover, we found an indirect association between close teacher
      child relationship quality and peer likability through children's social
      competence. The findings provide evidence that the teacher-child relationship is
      critical for children's social behaviors, and that social competence was uniquely
      related to peer likability.

PMID- 24039376
TI  - Late talking, typical talking, and weak language skills at middle childhood.
AB  - To better understand early predictors of weak language and academic abilities, we
      identified children with and without weak abilities at age 8. We then looked back
      at age 2 vocabulary and word combining, and evaluated these measures as
      predictors of age 8 outcomes. More than 60% of children with weak oral language
      abilities at 8 were not late talkers at 2. However, no word combining at 2 was a
      significant risk factor for poor oral language, reading comprehension, and math
      outcomes at 8. The association of no word combining with age 8 reading
      comprehension and math ability was mediated by age 8 oral language ability. The
      findings indicate that children take different developmental pathways to weak
      language abilities in middle childhood. One begins with a delayed onset of
      language. A second begins with language measures in the typical range, but ends
      with language ability falling well below typical peers.

PMID- 24039377
TI  - Gender Differences in Child Word Learning.
AB  - In prior work with adults, women were found to outperform men on a paired
      associates word-learning task, but only when learning phonologically-familiar
      novel words. The goal of the present work was to examine whether similar gender
      differences in word learning would be observed in children. In addition to
      manipulating phonological familiarity, referent familiarity was also manipulated.
      Children between the ages of 5 and 7 learned phonologically-familiar or
      phonologically-unfamiliar novel words in association with pictures of familiar
      referents (animals) or unfamiliar referents (aliens). Retention was tested via a
      forced-choice recognition measure administered immediately after the learning
      phase. Analyses of retention data revealed stronger phonological and referent
      familiarity effects in girls than in boys. Moreover, girls outperformed boys only
      when learning phonologically-familiar novel words and when learning novel words
      in association with familiar referents. These findings are interpreted to suggest
      that females are more likely than males to recruit native-language phonological
      and semantic knowledge during novel word learning.

PMID- 24039378
TI  - Evaluating Similarity Measures for Brain Image Registration.
AB  - Evaluation of similarity measures for image registration is a challenging problem
      due to its complex interaction with the underlying optimization, regularization,
      image type and modality. We propose a single performance metric, named
      robustness, as part of a new evaluation method which quantifies the effectiveness
      of similarity measures for brain image registration while eliminating the effects
      of the other parts of the registration process. We show empirically that
      similarity measures with higher robustness are more effective in registering
      degraded images and are also more successful in performing intermodal image
      registration. Further, we introduce a new similarity measure, called normalized
      spatial mutual information, for 3D brain image registration whose robustness is
      shown to be much higher than the existing ones. Consequently, it tolerates
      greater image degradation and provides more consistent outcomes for intermodal
      brain image registration.

PMID- 24039379
TI  - Onset to First Alcohol Use in Early Adolescence: A Network Diffusion Model.
AB  - A novel version of Snijders's stochastic actor-based modeling (SABM) framework is
      applied to model the diffusion of first alcohol use through middle school-wide
      longitudinal networks of early adolescents, aged approximately 11-14 years.
      Models couple a standard SABM for friendship network evolution with a
      proportional hazard model for first alcohol use. Meta-analysis of individual
      models for 12 schools found significant effects for friendship selection based on
      the same alcohol use status, and for an increased rate of onset to first use
      based on exposure to already-onset peers. Onset rate was greater at higher grades
      and among participants who spent more unsupervised time with friends. Neither
      selection nor exposure effects interacted with grade, adult supervision, or
      gender.

PMID- 24039380
TI  - Poultry growth modeling using neural networks and simulated data.
AB  - Poultry growth is usually modeled with the Gompertz model or another nonlinear
      statistical model using average BW data over certain periods of time for a given
      strain of birds under specific farm management conditions. Constant selection in
      the genetic pool, nutritional factors, and environmental concerns, however, make
      such models limited in their utility because of the difficulty of fitting the
      growth curve across time, bird strains, and other determining variables.
      Moreover, generating data for every strain of birds under continually changing
      variables is difficult, expensive, and time consuming. The current model
      addresses 2 objectives: to simulate data using published literature for different
      growth periods, and to develop artificial intelligence models with various neural
      network architectures. By breaking down the actual broiler growth data into 5-d
      intervals, with known means and SD, normal distributions were generated for
      broiler growth using @Risk software. These simulated data were then used to
      recognize data patterns and model growth curves by using various neural networks.
      Three neural networks, namely, BackPropagation-3 (3 layers of back propagation,
      with each layer connected to the previous layer), BackPropagation-5 (5 layers of
      back propagation, with each layer connected to the previous layer), and Ward-5 (5
      hidden slabs with various activation functions, using NeuroShell 2 Ward software)
      were used in this research. Once the networks were sufficiently trained, they
      were exposed to actual growth data to predict broiler growth over the next 50 d.
      The Back-Propagation-3 neural network gave the best fitting line, with
      predictions fitting tightly to the actual data points. The R2 was 0.998, and
      nearly perfect. The R2 for the BackPropagation-5 and Ward-5 neural networks were
      0.967 and 0.973, respectively. To test the approach further, the same methodology
      was applied in guinea fowl growth prediction, resulting in R2 of 0.96 both for
      the general regression and Ward-5 neural networks.

PMID- 24039382
TI  - A Path Algorithm for Constrained Estimation.
AB  - Many least-square problems involve affine equality and inequality constraints.
      Although there are a variety of methods for solving such problems, most
      statisticians find constrained estimation challenging. The current article
      proposes a new path-following algorithm for quadratic programming that replaces
      hard constraints by what are called exact penalties. Similar penalties arise in
      l1 regularization in model selection. In the regularization setting, penalties
      encapsulate prior knowledge, and penalized parameter estimates represent a trade
      off between the observed data and the prior knowledge. Classical penalty methods
      of optimization, such as the quadratic penalty method, solve a sequence of
      unconstrained problems that put greater and greater stress on meeting the
      constraints. In the limit as the penalty constant tends to infinity, one recovers
      the constrained solution. In the exact penalty method, squared penalties!are
      replaced by absolute value penalties, and the solution is recovered for a finite
      value of the penalty constant. The exact path-following method starts at the
      unconstrained solution and follows the solution path as the penalty constant
      increases. In the process, the solution path hits, slides along, and exits from
      the various constraints. Path following in Lasso penalized regression, in
      contrast, starts with a large value of the penalty constant and works its way
      downward. In both settings, inspection of the entire solution path is revealing.
      Just as with the Lasso and generalized Lasso, it is possible to plot the
      effective degrees of freedom along the solution path. For a strictly convex
      quadratic program, the exact penalty algorithm can be framed entirely in terms of
      the sweep operator of regression analysis. A few well-chosen examples illustrate
      the mechanics and potential of path following. This article has supplementary
      materials available online.

PMID- 24039383
TI  - On Differentially Private Frequent Itemset Mining.
AB  - We consider differentially private frequent itemset mining. We begin by exploring
      the theoretical difficulty of simultaneously providing good utility and good
      privacy in this task. While our analysis proves that in general this is very
      difficult, it leaves a glimmer of hope in that our proof of difficulty relies on
      the existence of long transactions (that is, transactions containing many items).
      Accordingly, we investigate an approach that begins by truncating long
      transactions, trading off errors introduced by the truncation with those
      introduced by the noise added to guarantee privacy. Experimental results over
      standard benchmark databases show that truncating is indeed effective. Our
      algorithm solves the "classical" frequent itemset mining problem, in which the
      goal is to find all itemsets whose support exceeds a threshold. Related work has
      proposed differentially private algorithms for the top-k itemset mining problem
      ("find the k most frequent itemsets".) An experimental comparison with those
      algorithms show that our algorithm achieves better F-score unless k is small.

PMID- 24039381
TI  - The costamere bridges sarcomeres to the sarcolemma in striated muscle.
AB  - Costameres are sub-membranous, Z-line associated structures found in striated
      muscle. They have been shown to have important roles in transmission of force
      from the sarcomere to the sarcolemma and extracellular matrix, maintaining
      mechanical integrity of the sarcolemma, and orchestrating mechanically related
      signaling. The costamere is akin to the more well-known focal adhesion complex
      present in most cells. The Z-line is a critical structural anchor for the
      sarcomere, but it is also a hot-spot for muscle cell signaling. Therefore
      functionally, the costamere represents a two-way signaling highway tethered
      between the Z-line and the extracellular matrix, relaying mechanical stress
      signals from outside the cell to intracellular signaling networks. In this role
      it can modulate myofibril growth and contraction. The major force generated by
      sarcomeres is transduced in the lateral direction from the sarcomere to the
      extracellular matrix through the costamere. Two major protein complexes have been
      described at the costamere: the dystrophin-glycoprotein complex and the integrin
      vinculin-talin complex. The importance of these two protein complexes in striated
      muscle function has between demonstrated both in human disease and mouse models.
      Members of the dystrophin glycoprotein complex and integrins have both been
      reported to interact directly with filamin-C, thus linking costameric complexes
      with those present at the Z-line. Moreover, studies from our labs and others have
      shown that the Z-line proteins belonging to the PDZ-LIM domain protein family,
      enigma homolog (ENH) and cypher, may directly or indirectly be involved in this
      linkage. The following review will focus on the protein components of this
      linkage, their function in force transmission, and how the dysfunction or loss of
      proteins within these complexes contributes to muscular disease.

PMID- 24039384
TI  - Trauma, Delinquency, and Substance Use: Co-occurring Problems for Adolescent
      Girls in the Juvenile Justice System.
AB  - Girls in the juvenile justice system are known to have high rates of co-occurring
      childhood abuse, trauma, and substance abuse. Girls with this constellation of
      problems are at high risk for serious adverse outcomes, including problems with
      drug dependence and abuse. The relationship between childhood sexual abuse,
      childhood physical abuse, other types of childhood trauma, and rates of substance
      use during adolescence were examined for girls in the juvenile justice system. As
      expected, childhood sexual abuse was significantly related to girls' substance
      use during adolescence. In contrast to prior research, no link was found between
      physical abuse, lifetime trauma, and substance use. Limitations and future
      directions are discussed.

PMID- 24039385
TI  - Estimating the Health Impact of Climate Change with Calibrated Climate Model
      Output.
AB  - Studies on the health impacts of climate change routinely use climate model
      output as future exposure projection. Uncertainty quantification, usually in the
      form of sensitivity analysis, has focused predominantly on the variability arise
      from different emission scenarios or multi-model ensembles. This paper describes
      a Bayesian spatial quantile regression approach to calibrate climate model output
      for examining to the risks of future temperature on adverse health outcomes.
      Specifically, we first estimate the spatial quantile process for climate model
      output using nonlinear monotonic regression during a historical period. The
      quantile process is then calibrated using the quantile functions estimated from
      the observed monitoring data. Our model also down-scales the gridded climate
      model output to the point-level for projecting future exposure over a specific
      geographical region. The quantile regression approach is motivated by the need to
      better characterize the tails of future temperature distribution where the
      greatest health impacts are likely to occur. We applied the methodology to
      calibrate temperature projections from a regional climate model for the period
      2041 to 2050. Accounting for calibration uncertainty, we calculated the number of
      of excess deaths attributed to future temperature for three cities in the US
      state of Alabama.

PMID- 24039386
TI  - Mapping temporal dynamics in social interactions with unified structural equation
      modeling: A description and demonstration revealing time-dependent sex
      differences in play behavior.
AB  - Developmental science is rich with observations of social interactions, but few
      available methodological and statistical approaches take full advantage of the
      information provided by these data. The authors propose implementation of the
      unified structural equation model (uSEM), a network analysis technique, for
      observational data coded repeatedly across time; uSEM captures the temporal
      dynamics underlying changes in behavior at the individual level by revealing the
      ways in which a single person influences - concurrently and in the future - other
      people. To demonstrate the utility of uSEM, the authors applied it to ratings of
      positive affect and vigor of activity during children's unstructured laboratory
      play with unfamiliar, same-sex peers. Results revealed the time-dependent nature
      of sex differences in play behavior. For girls more than boys, positive affect
      was dependent upon peers' prior positive affect. For boys more than girls, vigor
      of activity was dependent upon peers' current vigor of activity.

PMID- 24039387
TI  - Stimuli Sensitive Amphiphilic Dendrimers.
AB  - In the past decade, there has been an increasing interest in supramolecular
      systems that can undergo physical or chemical tranformations upon encountering a
      specific stimulus. Micelle-forming amphiphilic systems based on polymers and
      dendrimers are particularly preferred over small molecule amphiphiles, due to
      their ability to sequester and release a vast library of hydrophobic guest
      molecules at micromolar polymer or dendrimer concentrations. Here we review a
      relatively underexplored, yet rapidly advancing, field of amphiphilic systems
      based on dendritic architechture that exhibit stimuli sensitive behaviour. In
      particular, we will be focusing on stimuli such as temperature, pH, enzymatic and
      non-enzymatic proteins. These stimuli-responsive systems offer a unique
      opportunity in the field of drug delivery and sensing.

PMID- 24039388
TI  - Giant retinal tears after prior pars plana vitrectomy: management strategies and
      outcomes.
AB  - PURPOSE: To evaluate management strategies and outcomes for patients with giant
      retinal tear (GRT)-associated retinal detachment (RD) that had undergone previous
      pars plana vitrectomy (PPV). METHODS: A noncomparative consecutive case series
      between January 2005 and July 2010. Patients with a preceding history of PPV
      undergoing retinal reattachment surgery for GRTs were identified. RESULTS: Using
      International Classification of Diseases 9 codes for GRTs, 227 cases were
      identified. A total of eight eyes in eight patients were identified as having had
      preceding PPV for non-RD-related pathology. The mean age was 45.5 (range of 10
      79) years. The mean time between PPV and diagnosis of GRT was 2.4 months. The
      mean follow-up after RD surgery was 24.3 months. Presenting visual acuity was
      20/400 or better in four of eight patients (50%). All patients underwent repeat
      PPV with either gas or oil tamponade. A scleral buckling procedure was performed
      in seven patients (88%). Perfluorocarbon liquid was used during reattachment
      surgery in four patients (50%). Although anatomic success was achieved in all
      patients, visual acuity at last follow-up was 20/400 or better in 6 patients
      (75%). CONCLUSION: GRTs are an uncommon complication of PPV. The majority of
      patients underwent repeat PPV, scleral buckling procedure, perfluorocarbon liquid
      use and silicone-oil tamponade. Patients presenting with GRT-associated RD after
      PPV undergoing additional surgery achieved high rates of anatomic success, but
      visual outcomes were variable.

PMID- 24039389
TI  - Fusarium keratitis in Brazil: genotyping, in vitro susceptibilities, and clinical
      outcomes.
AB  - BACKGROUND: The purpose of this paper is to describe clinical characteristics and
      determine correlations between clinical outcomes and antifungal susceptibility
      among molecularly characterized ocular Fusarium isolates in Brazil. METHODS:
      Forty-one Fusarium isolates obtained from 41 eyes of 41 patients were retrieved
      from the ophthalmic microbiology laboratory at Sao Paulo Federal University and
      grown in pure culture. These isolates were genotyped and antifungal
      susceptibilities determined for each isolate using a broth microdilution method.
      The corresponding medical records were reviewed to determine clinical outcomes.
      RESULTS: The 41 isolates were genotypically classified as Fusarium solani species
      complex (36 isolates, 88%), Fusarium oxysporum species complex (two isolates,
      5%), Fusarium dimerum species complex (one isolate, 2%) and two isolates that did
      not group into any of the species complexes. Final best corrected visual acuity
      varied from 20/20 to light perception and was on average 20/800 (logarithm of the
      minimum angle of resolution (LogMAR) 1.6). A history of trauma was the most
      common risk factor, being present in 21 patients (51%). Therapeutic penetrating
      keratoplasty was necessary in 22 patients (54%). Amphotericin B had the lowest
      minimum inhibitory concentration for 90% of isolates (MIC90) value (2 MUg/mL) and
      voriconazole had the highest (16 MUg/mL). There was an association between a
      higher natamycin MIC and need for therapeutic penetrating keratoplasty (Mann
      Whitney test, P < 0.005). CONCLUSION: Trauma was the main risk factor, and
      therapeutic penetrating keratoplasty was necessary in 54% of patients.
      Amphotericin B had the lowest MIC90 (2 MUg/mL) of the three antifungal agents
      tested. There was an association between higher natamycin MIC levels and corneal
      perforation, emphasizing the need for antifungal susceptibility testing and
      tailoring of antifungal strategies.

PMID- 24039390
TI  - Two siblings with late-onset cone-rod dystrophy and no visible macular
      degeneration.
AB  - BACKGROUND: We report our findings in two siblings with late-onset cone-rod
      dystrophy (CRD) with no visible macular degeneration. CASES AND METHODS: Case 1
      was an 82-year-old man who first noticed a decrease in vision and color blindness
      in his early seventies. His mother and younger sister also had visual
      disturbances. His decimal visual acuity was 0.3 in the right eye and 0.2 in the
      left eye. Ophthalmoscopy showed normal fundi, and fluorescein angiography was
      also normal in both eyes. The photopic single flash and flicker eletroretinograms
      (ERGs) were severely attenuated and the scotopic ERGs were slightly reduced in
      both eyes. Case 2 was the 80-year-old younger sister of Case 1. She first noticed
      a decline in vision and photophobia in both eyes in her early seventies. Her
      decimal visual acuity was 0.4 in the right eye and 0.2 in the left eye.
      Ophthalmoscopy showed mottling of the retinal pigment epithelium in the
      midperiphery with no visible macular degeneration. The photopic single flash and
      flicker ERGs were severely attenuated, and the scotopic ERGs were slightly
      reduced in both eyes. CONCLUSION: These siblings are the oldest reported cases of
      CRD with no visible macular degeneration. Thus, CRD should be considered in
      patients with reduced visual acuity, color blindness, and photophobia even if
      they are older than 70 years.

PMID- 24039391
TI  - Efficacy of an artificial tear emulsion in patients with dry eye associated with
      meibomian gland dysfunction.
AB  - OBJECTIVES: The aim of the study reported here was to assess the efficacy of an
      artificial tear emulsion for the treatment of dry eye associated with meibomian
      gland dysfunction (MGD). METHODS: At five clinics, patients completed a 1-week
      treatment with their habitual topical therapy and then a 4-week treatment with
      open-label study medication: Systane(r) Balance Lubricant Eye Drops (Alcon, Alcon
      Inc, Fort Worth, TX, USA). Subjective assessments included a preference survey,
      the Impact of Dry Eye in Everyday Life questionnaire, and the Work Productivity
      and Activity Impairment questionnaire. Objective assessments by unmasked
      investigators included visual acuity, meibomian gland expression and dropout,
      tear film breakup time, corneal staining, and dosing frequency. RESULTS: At
      baseline, the 49 patients had mean meibomian gland expression grades and gland
      dropout that indicated mild to moderate MGD. Patients administered their habitual
      therapy 2.5 +/- 1.3 times per day. After 4 weeks of study medication, the Impact
      of Dry Eye in Everyday Life questionnaire results indicated statistically and
      clinically significant improvements. Fewer than half of the participants were
      employed, limiting the usefulness of the Work Productivity and Activity
      Impairment questionnaire. Visual acuity remained statistically similar, while
      corneal staining and tear film breakup time improved significantly (P < 0.05) but
      modestly. The outcomes were achieved with 1.9 +/- 1.1 doses per day of study
      medication, a significantly lower frequency than the habitual frequency (P <
      0.001). The most common medication-related adverse event was blurred vision (3/49
      patients, 6.1%). At study conclusion, 27/44 (61.4%) survey respondents preferred
      the study medication to their habitual therapy. CONCLUSION: The artificial tear
      emulsion was effective for treating the signs and symptoms of dry eye in MGD
      patients.

PMID- 24039392
TI  - Intravitreal moxifloxacin in the management of Ochrobactrum intermedium
      endophthalmitis due to metallic intraocular foreign body.
AB  - A healthy 34-year-old man presented with Ochrobactrum intermedium endophthalmitis
      due to a metallic intraocular foreign body. After vitrectomy, lensectomy, removal
      of the metallic intraocular foreign body, intravitreal vancomycin and
      ceftazidime, and systemic ciprofloxacin, intraocular inflammation worsened.
      Repeat vitreous culture confirmed persistent endophthalmitis due to multidrug
      resistant O. intermedium. The endophthalmitis successfully resolved after the
      administration of intravitreal moxifloxacin. 

PMID- 24039393
TI  - Optical coherence tomography classification of diabetic cystoid macular edema.
AB  - PURPOSE: To propose a new classification of diabetic cystoid macular edema (CME)
      based on optical coherence tomography (OCT) findings and cover all new important
      findings. PATIENTS AND METHODS: A retrospective study was carried out in the El
      Minia Investigation Eye Center between January 2012 and November 2012. It
      included 104 eyes of 86 patients, aged between 50 and 71 years, all with type II
      diabetes mellitus of duration from 5 to 20 years. All patients were diagnosed to
      have CME, as assessed by OCT, with measurement of the vertical size of the
      largest macular cyst and maximum macular thickness, and the relation between
      them. RESULTS: Patients were divided into four groups. Eyes with cysts less than
      30% of macular thickness were considered to have CME I (n = 4, 3.84%), while
      those between 30% and 60% were considered to have CME II (n = 62, 59.62%). Eyes
      with cysts between 60% and 90% of macular thickness were considered to have CME
      III (n = 36, 34.62%). CME IV was diagnosed when the size of the cyst became more
      than 90% of the macular thickness, and this was encountered in two eyes (1.92%).
      CONCLUSIONS: OCT is a useful technique for quantitative measurement and helps in
      better anatomical characterization of CME, and this classification of diabetic
      CME may be of value in classification of CME due to causes other than diabetes.

PMID- 24039394
TI  - Epidemiology and characteristics of childhood glaucoma: results from the Dallas
      Glaucoma Registry.
AB  - PURPOSE: Few studies have provided epidemiological characteristics of childhood
      glaucoma in a large, multiethnic population. This information is important if we
      are to better screen for and characterize this specific type of glaucoma. In this
      study, we evaluate the characteristics of patients with childhood glaucoma,
      including glaucoma suspects, as identified through the Dallas Glaucoma Registry
      (DGR). PATIENTS AND METHODS: The DGR catalogs the characteristics of glaucoma
      patients seen at University of Texas Southwestern Medical Center, an academic
      tertiary referral center for a large, multiethnic, urban population in the United
      States. We analyzed these patients with respect to race, medical and surgical
      treatment, cup-to-disc ratio, intraocular pressure, and visual outcomes. RESULTS:
      The study comprised 376 eyes of 239 childhood glaucoma patients, of whom 19% had
      primary congenital glaucoma, 4% had primary juvenile glaucoma, 45% had secondary
      glaucoma, and 31% were glaucoma suspects. Trauma and postsurgical aphakia were
      the most common causes for secondary glaucoma. Thirty-eight percent of patients
      were Hispanic, 30% were Caucasian, 21% were African American, 3% were Asian, and
      9% were unknown or unreported. Male sex was more common at 56%. Of all eyes with
      glaucoma, 65% received surgical intervention while 70% required at least one
      medication for intraocular pressure control. Trabeculotomy and tube-shunt surgery
      were the most common surgeries performed. Of patients who could have Snellen
      visual acuity measured, glaucoma suspect eyes had the largest proportion of eyes
      (96%) with good visual acuity (better than 20/40) while primary congenital
      glaucoma eyes had the smallest proportion (41%) with good visual acuity.
      Secondary glaucoma eyes had the largest proportion of eyes (30%) with poor visual
      acuity (worse than count fingers). CONCLUSION: The most common etiologies of
      childhood glaucoma were primary congenital glaucoma and secondary causes
      including trauma and postsurgical aphakia. A high proportion of glaucoma patients
      were of Hispanic background, reflecting the patient population studied.
      Trabeculotomy and tube-shunt surgery were the most common surgical interventions
      performed.

PMID- 24039395
TI  - Occult nonmetallic intraocular foreign bodies presenting as fulminant uveitis: a
      case series and review of the literature.
AB  - Intraocular foreign bodies (IOFBs) can complicate globe trauma and are associated
      with a high incidence of severe vision loss. Occult IOFBs present a particular
      challenge as they are not diagnosed promptly and tend to present with advanced
      complications, including endophthalmitis and retinal detachment. In this report,
      we present three cases of occult nonmetallic IOFBs presenting as fulminant
      uveitis, and we also review the literature. 

PMID- 24039396
TI  - Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study: findings
      at 3 months.
AB  - BACKGROUND: The purpose of this paper is to report the 3-month findings of the
      Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study. METHODS:
      Eighty eyes of 40 participants undergoing vitrectomy were enrolled. Participants
      underwent baseline evaluation of the study (surgical) and fellow (control) eye
      that included: intraocular pressure, central corneal thickness, gonioscopy, cup
      to-disc ratio measurement, color fundus and optic disc photography, automated
      perimetry, and optical coherence tomography of the macula and optic nerve.
      Evaluation was repeated at 3 months. Main outcome measures were changes in macula
      and retinal nerve fiber layer (RNFL) thickness and intraocular pressure. RESULTS:
      All participants completed follow-up. Mean cup-to-disc ratio of study and fellow
      eyes at baseline was 0.43 +/- 0.2 and 0.46 +/- 0.2, respectively, and 13% of
      participants had undiagnosed narrow angles. There was no significant change in
      intraocular pressure, cup-to-disc ratio, or pattern standard deviation in study
      eyes compared with baseline or fellow eyes at 3 months. Vision improved in all
      study eyes at 3 months compared with baseline (P = 0.013), but remained
      significantly worse than fellow eyes (P < 0.001). Central subfield and temporal
      peripapillary RNFL thickness were significantly greater in eyes with epiretinal
      membrane (P < 0.05), and resolution after surgery correlated with visual
      improvement (P < 0.05). CONCLUSION: The 3-month results do not indicate any
      increased risk for open-angle glaucoma but suggest that a relatively high
      percentage of eyes may be at risk of angle closure glaucoma. Temporal RNFL
      thickness and central subfield were increased in eyes with epiretinal membrane,
      and resolution correlated with degree of visual recovery.

PMID- 24039397
TI  - Preparation and in vivo absorption evaluation of spray dried powders containing
      salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery.
AB  - PURPOSE: The aim of the present study was to prepare inhalable co-spray dried
      powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs) with
      mannitol and investigate pulmonary absorption in rats. METHODS: The sCT-CS-NPs
      were prepared by the ionic gelation method using sodium tripolyphosphate (TPP) as
      a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying
      aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders
      were characterized with respect to morphology, particle size, powder density,
      aerodynamic diameter, protein integrity, in vitro release of sCT, and
      aerosolization. The plasmatic sCT levels following intratracheal administration
      of sCT-CS-NPs spray dried powders to the rats was also determined. RESULTS: sCT
      CS-NPs were able to be incorporated into mannitol forming inhalable
      microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and
      spray drying process affected the properties of the microparticles obtained. The
      conformation of the secondary structures of sCTs was affected by both mannitol
      content and spray dry inlet temperature. The sCT-CS-NPs were recovered after
      reconstitution of spray dried powders in an aqueous medium. The sCT release
      profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro
      inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS
      NPs spray dried powders having promising aerodynamic properties for deposition in
      the deep lung. Determination of the plasmatic sCT levels following intratracheal
      administration to rats revealed that the inhalable sCT-CS NPs spray dried powders
      provided higher protein absorption compared to native sCT powders. CONCLUSION:
      The sCT-CS-NPs with mannitol based spray dried powders were prepared to have
      appropriate aerodynamic properties for pulmonary delivery. The developed system
      was able to deliver sCT via a pulmonary route into the systemic circulation.

PMID- 24039398
TI  - Novel N-phenylcarbamothioylbenzamides with anti-inflammatory activity and
      prostaglandin E2 inhibitory properties.
AB  - A number of 2-((4-ethylphenoxy)methyl)-N-(substituted-phenylcarbamothioyl)
      benzamides (1a-h) were synthesized via reaction of 2-((4
      ethylphenoxy)methyl)benzoyl isothiocyanate (2) as a key intermediate with several
      substituted primary aromatic amines. The new compounds were characterized by
      proton nuclear magnetic resonance ((1)H-NMR), carbon-13 nuclear magnetic
      resonance ((13)C-NMR), infrared spectrometry (IR), mass spectrometry (MS), and
      elemental analysis. The anti-inflammatory activity of 1a-h was investigated by
      acute carrageenan-induced paw edema in mice using the reference drug
      indomethacin. The results obtained indicated that, of the derivatives developed,
      1a and 1d-h exhibited significantly higher anti-inflammatory activity (26.81%
      61.45%) when compared with the reference drug indomethacin (22.43%) (P = 0.0490
      for 1a, 0.0015 for 1d, 0.0330 for 1f, and P < 0.001 for 1e and 1h). Moreover, the
      ulcer incidence of 20% for 1e and 1h was clearly lower when compared with the
      indomethacin group (in which the ulcer incidence was 80%). Of particular note,
      the ulcer index of 0.2 for 1e was significantly less than that in the
      indomethacin group (0.6, P = 0.014). Additionally, prostaglandin E2 (PGE2)
      inhibitory properties were found to be high with 1e (68.32 pg/mL), significantly
      different from those of the placebo group (530.13 pg/mL, P < 0.001), and
      equipotent to the effect observed in the indomethacin-pretreated group (96.13
      pg/mL, P > 0.05). Moreover, the PGE2 level of 54.15 pg/mL with 1h was also
      significantly different from that of the placebo group (P < 0.001) and of the
      indomethacin group (P < 0.05). The significant inhibition of PGE2 observed with
      1e (68.32 pg/mL) and 1h (54.15 pg/mL) agree with their observed ulcer incidences.
      Our overall findings for N-phenylcarbamothioylbenzamides 1a-h clearly suggest
      that the compounds exhibit an anti-inflammatory effect, potently inhibit PGE2
      synthesis, and markedly demonstrate low ulcer incidence. 

PMID- 24039399
TI  - A review of sitagliptin with special emphasis on its use in moderate to severe
      renal impairment.
AB  - Sitagliptin is the first dipeptidylpeptidase-4 inhibitor to be used in the
      management of type 2 diabetes. It is widely used as an add-on therapy to ongoing
      management or as monotherapy where it is deemed necessary. It has been found to
      be beneficial in improving beta-cell function and glycemic control, and also is
      used in special circumstances like chronic kidney disease, with appropriate dose
      reductions. Overall, cardiovascular outcomes are no different from other oral
      hypoglycemic agents. In this review article we have summarized all the previous
      studies relevant to sitagliptin use in clinical practice and emphasized its use
      in various stages of chronic kidney disease. 

PMID- 24039400
TI  - Surfactant treatment before first breath for respiratory distress syndrome in
      preterm lambs: comparison of a peptide-containing synthetic lung surfactant with
      porcine-derived surfactant.
AB  - BACKGROUND: In a recent study utilizing a saline-lavaged adult rabbit model, we
      described a significant improvement in systemic oxygenation and pulmonary shunt
      after the instillation of a novel synthetic peptide-containing surfactant,
      Synsurf. Respiratory distress syndrome in the preterm lamb more closely resembles
      that of the human infant, as their blood gas, pH values, and lung mechanics
      deteriorate dramatically from birth despite ventilator support. Moreover,
      premature lambs have lungs which are mechanically unstable, with the advantage of
      being able to measure multiple variables over extended periods. Our objective in
      this study was to investigate if Synsurf leads to improved systemic oxygenation,
      lung mechanics, and histology in comparison to the commercially available porcine
      derived lung surfactant Curosurf(r) when administered before first breath in a
      preterm lamb model. MATERIALS AND METHODS: A Cesarean section was performed under
      general anesthesia on 18 time-dated pregnant Dohne Merino ewes at 129-130 days
      gestation. The premature lambs were delivered and ventilated with an expiratory
      tidal volume of 6-8 mL/kg for the first 30 minutes and thereafter at 8-10 mL/kg.
      In a randomized controlled trial, the two surfactants tested were Synsurf and
      Curosurf(r), both at a dose of 100 mg/kg phospholipids (1,2-dipalmitoyl-L-alpha
      phosphatidylcholine; 90% in Synsurf, 40% in Curosurf(r)). A control group of
      animals was treated with normal saline. Measurements of physiological variables,
      blood gases, and lung mechanics were made before and after surfactant and saline
      replacement and at 15, 30, 45, 60, 90, 120, 180, 240 and 300 minutes after
      treatment. The study continued for 5 hours. RESULTS: Surfactant treatment led to
      a significant improvement in oxygenation within 30 minutes, with the Synsurf
      group and the Curosurf(r) group having significantly higher ratios between
      arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2; P =
      0.021) compared to that of the control (saline-treated) animals. Dynamic
      compliance improved in the three groups over time, with no intergroup
      differences. All of the surfactant-treated animals survived, and one in the
      saline group died before the study ended. Histology between groups was not
      different, showing mild-moderate injury patterns. DISCUSSION: Treatment with
      surfactants before first breath clearly resulted in improved systemic oxygenation
      within 30 minutes of instillation. Both Synsurf- and Curosurf(r)-treated animals
      experienced similar and more sustained improvement in oxygenation and decreased
      calculated shunt compared to saline-treated animals.

PMID- 24039401
TI  - Identification of PPARgamma ligands with One-dimensional Drug Profile Matching.
AB  - INTRODUCTION: Computational molecular database screening helps to decrease the
      time and resources needed for drug development. Reintroduction of generic drugs
      by second medical use patents also contributes to cheaper and faster drug
      development processes. We screened, in silico, the Food and Drug Administration
      approved generic drug database by means of the One-dimensional Drug Profile
      Matching (oDPM) method in order to find potential peroxisome proliferator
      activated receptor gamma (PPARgamma) agonists. The PPARgamma action of the
      selected generics was also investigated by in vitro and in vivo experiments.
      MATERIALS AND METHODS: The in silico oDPM method was used to determine the
      binding potency of 1,255 generics to 149 proteins collected. In vitro PPARgamma
      activation was determined by measuring fatty acid-binding protein 4/adipocyte
      protein gene expression in a Mono Mac 6 cell line. The in vivo insulin
      sensitizing effect of the selected compound (nitazoxanide; 50-200 mg/kg/day over
      8 days; n = 8) was established in type 2 diabetic rats by hyperinsulinemic
      euglycemic glucose clamping. RESULTS: After examining the closest neighbors of
      each of the reference set's members and counting their most abundant neighbors,
      ten generic drugs were selected with oDPM. Among them, four enhanced fatty acid
      binding protein/adipocyte protein gene expression in the Mono Mac 6 cell line,
      but only bromfenac and nitazoxanide showed dose-dependent actions. Induction by
      nitazoxanide was higher than by bromfenac. Nitazoxanide lowered fasting blood
      glucose levels and improved insulin sensitivity in type 2 diabetic rats.
      CONCLUSION: We demonstrated that the oDPM method can predict previously unknown
      therapeutic effects of generic drugs. Nitazoxanide can be the prototype chemical
      structure of the new generation of insulin sensitizers.

PMID- 24039402
TI  - Development, clinical utility, and place of ivacaftor in the treatment of cystic
      fibrosis.
AB  - Cystic fibrosis (CF) is a life-limiting, multisystem disease characterized by
      thick viscous secretions leading to recurrent lung infections, bronchiectasis,
      and progressive deterioration in lung function. CF is caused by loss or
      dysfunction of the CF transmembrane conductance regulator (CFTR) protein which is
      responsible for transepithelial chloride and water transport. Improved
      understanding of CFTR protein dysfunction has allowed the development of mutation
      specific small-molecule compounds which directly target the underlying CFTR
      defect. Ivacaftor is the first licensed small-molecule compound for CF patients
      which targets the CFTR gating mutation Gly551Asp (previously termed G551D) and
      has the potential to be truly disease-modifying. Ivacaftor is an oral medication
      given twice daily and has shown benefit in terms of an increase in lung function,
      decreased sweat chloride, weight gain, improvement in patient-reported quality of
      life, and reduction in number of respiratory exacerbations in clinical trials.
      Although ivacaftor is currently only licensed for use in approximately 5% of the
      CF population (those who have at least one Gly551Asp mutation), the developmental
      pathway established by ivacaftor paves the way for other CFTR modulators that may
      benefit many more patients. In particular, a CFTR modulator for those with the
      Phe508del deletion (previously ?F508) would allow 90% of the CF population to
      benefit from disease-modifying treatment. 

PMID- 24039403
TI  - Intravenous iron monotherapy for the treatment of non-iron-deficiency anemia in
      cancer patients undergoing chemotherapy: a pilot study.
AB  - BACKGROUND: Anemia in patients with cancer who are undergoing active therapy is
      commonly encountered and may worsen quality of life in these patients. The effect
      of blood transfusion is often temporary and may be associated with serious
      adverse events. Erythropoiesis-stimulating agents are not effective in 30%-50% of
      patients and may have a negative effect on overall survival. AIMS: To assess the
      efficacy and feasibility of intravenous iron therapy in patients with cancer who
      have non-iron-deficiency anemia and who are undergoing treatment with
      chemotherapy without the use of erythropoiesis-stimulating agents. METHODS: Adult
      patients with solid cancers and non-iron-deficiency anemia were included. Ferric
      sucrose at a dose of 200 mg was given in short intravenous infusions weekly for a
      total of 12 weeks. Hemoglobin level was measured at baseline, every 3 weeks, and
      2 weeks after the last iron infusion (week 14). Adverse events related to
      intravenous iron were prospectively reported. RESULTS: Of 25 patients included,
      19 (76.0%) completed at least three iron infusions and 14 (56.0%) finished the
      planned 12 weeks of therapy. The mean hemoglobin level of the 25 patients at
      baseline was 9.6 g/dL (median, 9.9 g/dL; range, 6.9 g/dL 10.9 g/dL). The mean
      change in hemoglobin level for the 15 patients who completed at least 9
      treatments was 1.7 g/dL (median, 1.1 g/dL; range, -1.9 g/dL to 3.2 g/dL); it
      reached 2.1 g/dL (median, 1.3 g/dL; range, -0.2 g/dL to 4.6 g/dL; P = 0.0007) for
      the 14 patients who completed all 12 weekly treatments. Five (20.0%) patients
      were transfused and considered as treatment failures. No treatment-related
      adverse events were reported. CONCLUSION: Intravenous iron treatment alone is
      safe and may reduce blood transfusion requirements and improve hemoglobin level
      in patients with cancer who are undergoing anticancer therapy. Further randomized
      studies are needed to confirm these findings.

PMID- 24039404
TI  - Dissolving and biodegradable microneedle technologies for transdermal sustained
      delivery of drug and vaccine.
AB  - Microneedles were first conceptualized for drug delivery many decades ago,
      overcoming the shortages and preserving the advantages of hypodermic needle and
      conventional transdermal drug-delivery systems to some extent. Dissolving and
      biodegradable microneedle technologies have been used for transdermal sustained
      deliveries of different drugs and vaccines. This review describes microneedle
      geometry and the representative dissolving and biodegradable microneedle delivery
      methods via the skin, followed by the fabricating methods. Finally, this review
      puts forward some perspectives that require further investigation. 

PMID- 24039405
TI  - Hologram quantitative structure-activity relationship and comparative molecular
      field analysis studies within a series of tricyclic phthalimide HIV-1 integrase
      inhibitors.
AB  - Acquired immunodeficiency syndrome is a public health problem worldwide caused by
      the Human immunodeficiency virus (HIV). Treatment with antiretroviral drugs is
      the best option for viral suppression, reducing morbidity and mortality. However,
      viral resistance in HIV-1 therapy has been reported. HIV-1 integrase (IN) is an
      essential enzyme for effective viral replication and an attractive target for the
      development of new inhibitors. In the study reported here, two- and three
      dimensional quantitative structure-activity relationship (2D/3D-QSAR) studies,
      applying hologram quantitative structure-activity relationship (HQSAR) and
      comparative molecular field analysis (CoMFA) methods, respectively, were
      performed on a series of tricyclic phthalimide HIV-1 IN inhibitors. The best
      HQSAR model (q (2) = 0.802, r (2) = 0.972) was obtained using atoms, bonds, and
      connectivity as the fragment distinction, a fragment size of 2-5 atoms, hologram
      length of 61 bins, and six components. The best CoMFA model (q (2) = 0.748, r (2)
      = 0.974) was obtained with alignment of all atoms of the tricyclic phthalimide
      moiety (alignment II). The HQSAR contribution map identified that the carbonyl
      hydroxy-aromatic nitrogen motif made a positive contribution to the activity of
      the compounds. Furthermore, CoMFA contour maps suggested that bulky groups in
      meta and para positions in the phenyl ring would increase the biological activity
      of this class. The conclusions of this work may lead to a better understanding of
      HIV-1 IN inhibition and contribute to the design of new and more potent
      derivatives. 

PMID- 24039406
TI  - Long-acting preparations of exenatide.
AB  - Exenatide has been widely used for the treatment of type 2 diabetes mellitus.
      However, its short plasma half-life of 2.4 hours has limited its clinical
      application. The exenatide products on the market, twice-daily ByettaTM and once
      weekly BydureonTM (both Amylin Pharmaceuticals, San Diego, CA, USA), are still
      not perfect. Many researchers have attempted to prolong the acting time of
      exenatide by preparing sustained-release dosage forms, modifying its structure,
      gene therapies, and other means. This review summarizes recent advances in long
      acting exenatide preparations. 

PMID- 24039407
TI  - User-centered development and testing of a monitoring system that provides
      feedback regarding physical functioning to elderly people.
AB  - PURPOSE: To involve elderly people during the development of a mobile interface
      of a monitoring system that provides feedback to them regarding changes in
      physical functioning and to test the system in a pilot study. METHODS AND
      PARTICIPANTS: The iterative user-centered development process consisted of the
      following phases: (1) selection of user representatives; (2) analysis of users
      and their context; (3) identification of user requirements; (4) development of
      the interface; and (5) evaluation of the interface in the lab. Subsequently, the
      monitoring and feedback system was tested in a pilot study by five patients who
      were recruited via a geriatric outpatient clinic. Participants used a bathroom
      scale to monitor weight and balance, and a mobile phone to monitor physical
      activity on a daily basis for six weeks. Personalized feedback was provided via
      the interface of the mobile phone. Usability was evaluated on a scale from 1 to 7
      using a modified version of the Post-Study System Usability Questionnaire
      (PSSUQ); higher scores indicated better usability. Interviews were conducted to
      gain insight into the experiences of the participants with the system. RESULTS:
      The developed interface uses colors, emoticons, and written and/or spoken text
      messages to provide daily feedback regarding (changes in) weight, balance, and
      physical activity. The participants rated the usability of the monitoring and
      feedback system with a mean score of 5.2 (standard deviation 0.90) on the
      modified PSSUQ. The interviews revealed that most participants liked using the
      system and appreciated that it signaled changes in their physical functioning.
      However, usability was negatively influenced by a few technical errors.
      CONCLUSION: Involvement of elderly users during the development process resulted
      in an interface with good usability. However, the technical functioning of the
      monitoring system needs to be optimized before it can be used to support elderly
      people in their self-management.

PMID- 24039408
TI  - Utilities associated with subcutaneous injections and intravenous infusions for
      treatment of patients with bone metastases.
AB  - INTRODUCTION: Although cost-utility models are often used to estimate the value
      of treatments for metastatic cancer, limited information is available on the
      utility of common treatment modalities. Bisphosphonate treatment for bone
      metastases is frequently administered via intravenous infusion, while a newer
      treatment is administered as a subcutaneous injection. This study estimated the
      impact of these treatment modalities on health state preference. METHODS:
      Participants from the UK general population completed time trade-off interviews
      to assess the utility of health state vignettes. Respondents first rated a health
      state representing cancer with bone metastases. Subsequent health states added
      descriptions of treatment modalities (ie, injection or infusion) to this basic
      health state. The two treatment modalities were presented with and without
      chemotherapy, and infusion characteristics were varied by duration (30 minutes or
      2 hours) and renal monitoring. RESULTS: A total of 121 participants completed the
      interviews (52.1% female, 76.9% white). Cancer with bone metastases had a mean
      utility of 0.40 on a standard utility scale (1 = full health; 0 = dead). The
      injection, 30-minute infusion, and 2-hour infusion had mean disutilities of 
      0.004, -0.02, and -0.04, respectively. The mean disutility of the 30-minute
      infusion was greater with renal monitoring than without. Chemotherapy was
      associated with substantial disutility (-0.17). When added to health states with
      chemotherapy, the mean disutilities of injection, 30-minute infusion, and 2-hour
      infusion were -0.02, -0.03, and -0.04, respectively. The disutility associated
      with injection was significantly lower than the disutility of the 30-minute and 2
      hour infusions (P < 0.05), regardless of chemotherapy status. CONCLUSION:
      Respondents perceived an inconvenience with each type of treatment modality, but
      injections were preferred over infusions. The resulting utilities may be used in
      cost-utility models examining the value of treatments for the prevention of
      skeletal-related events in patients with bone metastases.

PMID- 24039409
TI  - A randomized, double-masked study to evaluate the effect of omega-3 fatty acids
      supplementation in meibomian gland dysfunction.
AB  - BACKGROUND: Dysfunction of the meibomian gland (MG) is among the most frequent
      causes of ophthalmological symptoms. The inflammation seen in meibomian gland
      dysfunction (MGD) is part of its pathogenesis, and evidence of the antioxidant
      inflammatory properties of omega-3 fatty acids suggests this to be an appropriate
      treatment for MGD. OBJECTIVE: We aimed to assess the effectiveness of omega-3
      fatty acids versus placebo, in improving the symptoms and signs of MGD. METHODS:
      We conducted a randomized and double-mask trial of 3 months duration. We enrolled
      61 patients who presented with symptomatic MGD and no tear instability (defined
      as tear breakup time [TBUT] <10 seconds). Participants were randomly assigned to
      two homogeneous subgroups. For patients in group A, the study treatment included
      cleaning the lid margins with neutral baby shampoo and use of artificial tears
      without preservatives, plus a placebo oral agent. For patients in group B, the
      study treatment included cleaning the lid margins with neutral baby shampoo and
      use of artificial tears without preservatives, plus oral supplementation with
      omega-3 fatty acids. We performed the following tests: (1) TBUT; (2) Schirmer I
      test; (3) Ocular Surface Disease Index(c) (OSDI(c); Allergan, Inc., Irvine, CA,
      USA); (4) MG expression; (5) evaluation of lid margin inflammation; and (6)
      interpalpebral and corneal dye staining. RESULTS: After 3 months of evaluation,
      the mean OSDI, TBUT, lid margin inflammation, and MG expression presented
      improvement from the baseline values, in group B (P < 0.01, P < 0.001, P <
      0.0001, P < 0.0001, respectively). The Schirmer test results were also improved
      and statistically significant (P < 0.01). CONCLUSION: Oral omega-3 fatty acids,
      1.5 grams per day, may be beneficial in the treatment of MGD, mainly by improving
      tear stability.

PMID- 24039410
TI  - Clinical investigation of transradial access for emergent percutaneous coronary
      intervention in patients with acute myocardial infarction.
AB  - BACKGROUND: Use of intensive anticoagulation and antiplatelet therapy in acute
      myocardial infarction (AMI) potentially increases the risk of bleeding
      complications during percutaneous coronary intervention via the transfemoral
      route. Recently, the transradial access has been intensively employed as an
      alternative means for diagnostic and interventional procedures. A low incidence
      of vascular access site bleeding complications suggests that the transradial
      access is a safe alternative to the transfemoral technique in patients with AMI.
      The safety and efficacy of transradial access for emergent percutaneous coronary
      intervention in patients with AMI has not been investigated in the People's
      Republic of China. METHODS: We analyzed data from our single-center registry on
      596 consecutive patients between October 2003 and October 2010. The patients were
      retrospectively divided into a transradial group (n = 296) and a transfemoral
      group (n = 300). A dedicated doctor was appointed to collect the following data:
      puncture time, coronary angiography time, percutaneous coronary intervention
      time, X-ray exposure time, duration of hospitalization, and complication rates
      associated with puncture, such as puncture site bleeding, hematoma,
      pseudoaneurysm, and major adverse cardiac events. RESULTS: There were no
      significant differences in baseline characteristics and angiographic findings
      between the two groups. There were also no significant differences in coronary
      angiography time (8.2 +/- 2.4 versus 7.6 +/- 2.0 minutes), percutaneous coronary
      intervention time (30 +/- 6.8 versus 29.6 +/- 8.1 minutes), or X-ray exposure
      time (4.6 +/- 1.4 versus 4.4 +/- 1.3 minutes) between the groups. There were
      significant differences in puncture time (4.4 +/- 1.6 versus 2.4 +/- 0.8 minutes)
      and duration of hospitalization (3.2 +/- 1.6 versus 5.4 +/- 1.8 days) between the
      groups (P < 0.001). The complication rate using transradial access was 2.03%
      (6/296) versus 6.0% (18/300) using transfemoral access (P < 0.0001). CONCLUSION:
      Transradial access for emergent percutaneous coronary intervention is safe and
      effective in patients with AMI, and it is suggested that this route could be used
      more widely in these patients.

PMID- 24039411
TI  - Insufficient amounts and inadequate distribution of dietary protein intake in
      apparently healthy older adults in a developing country: implications for dietary
      strategies to prevent sarcopenia.
AB  - BACKGROUND: Both low dietary protein intake and inadequate distribution of
      protein over the three mealtimes have been reported in older Caucasian adults,
      but the association between protein intake at each meal and muscle mass has not
      been studied. The purpose of this study was to evaluate dietary protein intake
      and distribution by mealtimes, and to explore their association with appendicular
      skeletal muscle mass in apparently healthy older adults. METHODS: This was a
      cross-sectional pilot study that included 78 people over the age of 60 years.
      Caloric and protein intake were estimated on the basis of three nonconsecutive 24
      hour diet recalls and appendicular skeletal muscle mass by dual-energy X-ray
      absorptiometry. RESULTS: Men consumed 13.4 g of protein/day more than women (P <
      0.05). The estimated value of dietary protein intake was 0.9 g/kg/day. In this
      sample, 28% of subjects did not cover 100% of the dietary reference intake for
      protein. Lower consumption of dietary protein was found at breakfast and
      dinnertime compared with the recommended amount of 25-30 g (P < 0.05). Also, the
      study observed that appendicular skeletal muscle mass in men and women who
      consumed <25 g of protein at each mealtime was different from that found in the
      group that consumed >25 g of protein at one, two, or three mealtimes. CONCLUSION:
      While protein intake was higher than current recommendations, it failed to
      achieve the values reported as necessary to prevent sarcopenia. In addition,
      there was under-consumption of protein per mealtime, especially at breakfast and
      dinner.

PMID- 24039412
TI  - Perioral rejuvenation: restoration of attractiveness in aging females by
      minimally invasive procedures.
AB  - Lips and the perioral area are of outstanding importance in youthful appearance,
      attractiveness, and beauty. In contrast to younger and middle aged females, there
      is only scant published data on minimally invasive procedures to restore and
      revitalize lips and perioral soft tissue in elderly females. In this review we
      report the signs of aging in this particular region and the underlying anatomy.
      We review studies on lip restoration in younger females and present our
      techniques for elderly women. With an individually tailored approach, elderly
      females benefit from minimally invasive techniques. 

PMID- 24039413
TI  - A quasi-experimental study on a new service option for short-term residential
      care of older stroke patients.
AB  - We conducted a quasi-experimental study to compare the effectiveness of a new
      short-term residential care option for stroke rehabilitation with that of usual
      day hospital care. Primary data were collected from stroke patients and their
      caregivers from June 2009 to May 2012. New service option users and their
      caregivers were recruited for the intervention group, while users of usual public
      geriatric day hospital care and their caregivers were recruited for the control
      group. The primary outcome measures were Modified Barthel Index (MBI) and Mini
      Mental Status Examination (MMSE) scores. Trained research assistants assessed the
      outcome measures at the beginning of the rehabilitation program (baseline) and at
      a 4-month follow-up. Sixty and 128 stroke patients were recruited for the
      intervention and control groups, respectively; 50 and 105 participants,
      respectively, completed the 4-month follow-up. At 4-month follow-up, the
      intervention group had an increased MBI score of 15.3 (95% confidence interval
      [CI] 10.8-19.8) and an MMSE score of 1.3 (95% CI 0.4-2.1). In comparison, the
      control group had an increased MBI score of 13.3 (95% CI 9.7-16.8) and an MMSE
      score of 1.1 (95% CI 0.4-1.9). Both groups showed a significant improvement in
      MBI and MMSE scores after 4 months, and there was no significant between-group
      difference. To conclude, the new service option and the usual care option showed
      similar improvement in rehabilitation outcomes at 4 months after baseline.
      Initiatives to provide alternative care options on a user-pay model should be
      encouraged to ensure a sustainable health care system. 

PMID- 24039414
TI  - Quantitative assessment of walking time and postural change in patients with COPD
      using a new triaxial accelerometer system.
AB  - BACKGROUND: The purpose of this study was to quantify the walking time and
      frequency of postural changes in daily life in patients with chronic obstructive
      pulmonary disease (COPD) using a new triaxial accelerometer system. METHODS:
      Twenty-six elderly patients with stable COPD (age 76.8 +/- 6.2 years; percent
      forced expiratory volume in one second [%FEV1] 52.9% +/- 26.3%) and 20 age
      matched elderly subjects (age 73.0 +/- 4.2 years; %FEV1 124.0% +/- 22.3%)
      participated in the study. The subjects' time spent walking (slow, fast),
      standing, sitting, and lying down and the frequency of their postural changes
      (getting up, standing up) were assessed for 7 consecutive days using an Activity
      Monitoring And Evaluation System (A-MESTM). We analyzed the relationships among
      walking times, frequency of postural changes, and physiologic factors in both
      COPD patients and controls. RESULTS: The COPD patients' total walking time,
      including slow (<2 km/hour) and fast (>=2 km/hour) walking, and their frequency
      of standing up were significantly lower than those of the age-matched controls (P
      < 0.01). The fast walking time in daily life was significantly correlated with
      the 6-minute walking distance, quadriceps femoris muscle force, and dyspnea (P <
      0.01). CONCLUSION: These results suggest that both slow (<2 km/hour) and fast
      (>=2 km/hour) walking time and frequency of postural changes is significantly
      decreased in COPD patients compared with healthy elderly subjects. The data also
      suggest that the COPD patients' different walking times in daily life are
      significantly correlated with exercise capacity and dyspnea. The 6-minute walking
      distance had the strongest correlation with fast walking time.

PMID- 24039415
TI  - Nanostructured polyurethane-poly-lactic-co-glycolic acid scaffolds increase
      bladder tissue regeneration: an in vivo study.
AB  - Although showing much promise for numerous tissue engineering applications,
      polyurethane and poly-lactic-co-glycolic acid (PLGA) have suffered from a lack of
      cytocompatibility, sometimes leading to poor tissue integration. Nanotechnology
      (or the use of materials with surface features or constituent dimensions less
      than 100 nm in at least one direction) has started to transform currently
      implanted materials (such as polyurethane and PLGA) to promote tissue
      regeneration. This is because nanostructured surface features can be used to
      change medical device surface energy to alter initial protein adsorption events
      important for promoting tissue-forming cell functions. Thus, due to their altered
      surface energetics, the objective of the present in vivo study was to create
      nanoscale surface features on a new polyurethane and PLGA composite scaffold (by
      soaking the polyurethane side and PLGA side in HNO3 and NaOH, respectively) and
      determine bladder tissue regeneration using a minipig model. The novel
      nanostructured scaffolds were further functionalized with IKVAV and YIGSR
      peptides to improve cellular responses. Results provided the first evidence of
      increased in vivo bladder tissue regeneration when using a composite of
      nanostructured polyurethane and PLGA compared with control ileal segments. Due to
      additional surgery, extended potentially problematic healing times, metabolic
      complications, donor site morbidity, and sometimes limited availability, ileal
      segment repair of a bladder defect is not optimal and, thus, a synthetic analog
      is highly desirable. In summary, this study indicates significant promise for the
      use of nanostructured polyurethane and PLGA composites to increase bladder tissue
      repair for a wide range of regenerative medicine applications, such as
      regenerating bladder tissue after removal of cancerous tissue, disease, or other
      trauma.

PMID- 24039416
TI  - The anticancer properties of iron core-gold shell nanoparticles in colorectal
      cancer cells.
AB  - Previously, iron core-gold shell nanoparticles (Fe@Au) have been shown to possess
      cancer-preferential cytotoxicity in oral and colorectal cancer (CRC) cells.
      However, CRC cell lines are less sensitive to Fe@Au treatment when compared with
      oral cancer cell lines. In this research, Fe@Au are found to decrease the cell
      viability of CRC cell lines, including Caco-2, HT-29, and SW480, through growth
      inhibition rather than the induction of cell death. The cytotoxicity induced by
      Fe@Au in CRC cells uses different subcellular pathways to the mitochondria
      mediated autophagy found in Fe@Au-treated oral cancer cells, OECM1.
      Interestingly, the Caco-2 cell line shows a similar response to OECM1 cells and
      is thus more sensitive to Fe@Au treatment than the other CRC cell lines studied.
      We have investigated the underlying cell resistance mechanisms of Fe@Au-treated
      CRC cells. The resistance of CRC cells to Fe@Au does not result from the total
      amount of Fe@Au internalized. Instead, the different amounts of Fe and Au
      internalized appear to determine the different response to treatment with Fe-only
      nanoparticles in Fe@Au-resistant CRC cells compared with the Fe@Au-sensitive
      OECM1 cells. The only moderately cytotoxic effect of Fe@Au nanoparticles on CRC
      cells, when compared to the highly sensitive OECM1 cells, appears to arise from
      the CRC cells' relative insensitivity to Fe, as is demonstrated by our Fe-only
      treatments. This is a surprising outcome, given that Fe has thus far been
      considered to be the "active" component of Fe@Au nanoparticles. Instead, we have
      found that the Au coatings, previously considered only as a passivating coating
      to protect the Fe cores from oxidation, significantly enhance the cytotoxicity of
      Fe@Au in certain CRC cells. Therefore, we conclude that both the Fe and Au in
      these core-shell nanoparticles are essential for the anticancer properties
      observed in CRC cells. 

PMID- 24039417
TI  - Silymarin-loaded solid nanoparticles provide excellent hepatic protection:
      physicochemical characterization and in vivo evaluation.
AB  - BACKGROUND: The purpose of this study was to develop a novel silymarin-loaded
      solid nanoparticle system with enhanced oral bioavailability and an ability to
      provide excellent hepatic protection for poorly water-soluble drugs using Shirasu
      porous glass (SPG) membrane emulsification and a spray-drying technique. METHODS:
      A silymarin-loaded liquid nanoemulsion was formulated by applying the SPG
      membrane emulsification technique. This was further converted into solid state
      nanosized particles by the spray-drying technique. The physicochemical
      characteristics of these nanoparticles were determined by scanning electron
      microscopy, differential scanning calorimetry, and powder X-ray diffraction.
      Their dissolution, bioavailability, and hepatoprotective activity in rats were
      assessed by comparison with a commercially available silymarin-loaded product.
      RESULTS: Formulation of a silymarin-loaded nanoemulsion, comprising silymarin,
      castor oil, polyvinylpyrrolidone, Transcutol HP, Tween 80, and water at a weight
      ratio of 5/3/3/1.25/1.25/100 was accomplished using an SPG membrane
      emulsification technique at an agitator speed of 700 rpm, a feed pressure of 15
      kPa, and a continuous phase temperature of 25 degrees C. This resulted in
      generation of comparatively uniform emulsion globules with a narrow size
      distribution. Moreover, the silymarin-loaded solid nanoparticles, containing
      silymarin/castor oil/polyvinylpyrrolidone/Transcutol HP/Tween 80 at a weight
      ratio of 5/3/3/1.25/1.25, improved about 1,300-fold drug solubility and retained
      a mean size of about 210 nm. Silymarin was located in unaltered crystalline form
      in the nanoparticles. The drug dissolved rapidly from the nanoparticles, reaching
      nearly 80% within 15 minutes, indicating three-fold better dissolution than that
      of the commercial product. Further, the nanoparticles showed a considerably
      shorter time to peak concentration, a greater area under the concentration-time
      curve, and a higher maximum concentration of silymarin compared with the
      commercial product (P < 0.05). In particular, the area under the concentration
      time curve of the drug provided by the nanoparticles was approximately 1.3-fold
      greater than that of the commercial product. In addition, the silymarin-loaded
      nanoparticles significantly reduced carbon tetrachloride-induced hepatotoxicity,
      indicating improved bioactivity compared with silymarin powder and the commercial
      product. CONCLUSION: Silymarin-loaded nanoparticles developed using SPG membrane
      emulsification and spray-drying techniques could be a useful system for delivery
      of poorly water-soluble silymarin while affording excellent hepatic protection.

PMID- 24039418
TI  - Nicotinamide-functionalized multiwalled carbon nanotubes increase insulin
      production in pancreatic beta cells via MIF pathway.
AB  - Recent data in the literature support the role of nicotinamide (NA) as a
      pharmacologic agent that stimulates pancreatic beta-cells to produce insulin in
      vitro. There are data showing that carbon nanotubes may be useful in initiating
      and maintaining cellular metabolic responses. This study shows that
      administration of multiwalled carbon nanotubes (MWCNTs) functionalized with
      nicotinamide (NA-MWCNTs) leads to significant insulin production compared with
      individual administration of NA, MWCNTs, and a control solution. Treatment of
      1.4E7 cells for 30 minutes with NA-MWCNTs at concentrations ranging from 1 mg/L
      to 20 mg/L resulted in significantly increased insulin release (0.18 +/- 0.026
      ng/mL for 1 mg/L, 0.21 +/- 0.024 ng/mL for 5 mg/L, and 0.27 +/- 0.028 ng/mL for
      20 mg/L). Thus, compared with cells treated with NA only (0.1 +/- 0.01 ng/mL for
      1 mg/L, 0.12 +/- 0.017 ng/mL for 5 mg/L, and 0.17 +/- 0.01 ng/mL for 20 mg/L) we
      observed a significant positive effect on insulin release in cells treated with
      NA-MWCNTs. The results were confirmed using flow cytometry, epifluorescence
      microscopy combined with immunochemistry staining, and enzyme-linked
      immunosorbent assay techniques. In addition, using immunofluorescence microscopy
      techniques, we were able to demonstrate that MWCNTs enhance insulin production
      via the macrophage migration inhibitory factor pathway. The application and
      potential of NA combined with MWCNTs as an antidiabetic agent may represent the
      beginning of a new chapter in the nanomediated treatment of diabetes mellitus. 

PMID- 24039419
TI  - Biogenic silver nanoparticles using Rhinacanthus nasutus leaf extract: synthesis,
      spectral analysis, and antimicrobial studies.
AB  - Nanotechnology is gaining momentum due to its ability to transform metals into
      nanoparticles. The synthesis, characterization, and applications of biologically
      synthesized nanomaterials have become an important branch of nanotechnology.
      Plant extracts are a cost-effective, ecologically friendly, and efficient
      alternative for the large-scale synthesis of nanoparticles. In this study, silver
      nanoparticles (AgNps) were synthesized using Rhinacanthus nasutus leaf extract.
      After exposing the silver ions to the leaf extract, the rapid reduction of silver
      ions led to the formation of AgNps in solution. The synthesis was confirmed by
      ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, and
      transmission electron microscopy. The in vitro antimicrobial activity of the
      AgNps synthesized using R. nasutus leaf extract was investigated against Bacillus
      subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia,
      Escherichia coli, Aspergillus niger, and Aspergillus flavus using a disc
      diffusion method. The AgNps showed potential activity against all of the
      bacterial strains and fungal colonies, indicating that R. nasutus has the
      potential to be used in the development of value-added products in the biomedical
      and nanotechnology-based industries. 

PMID- 24039420
TI  - A physiologically based pharmacokinetic model for ionic silver and silver
      nanoparticles.
AB  - Silver is a strong antibiotic that is increasingly incorporated into consumer
      products as a bulk, salt, or nanosilver, thus potentially causing side-effects
      related to human exposure. However, the fate and behavior of (nano)silver in the
      human body is presently not well understood. In order to aggregate the existing
      experimental information, a physiologically based pharmacokinetic model (PBPK)
      was developed in this study for ionic silver and nanosilver. The structure of the
      model was established on the basis of toxicokinetic data from intravenous
      studies. The number of calibrated parameters was minimized in order to enhance
      the predictive capability of the model. We validated the model structure for both
      silver forms by reproducing exposure conditions (dermal, oral, and inhalation) of
      in vivo experiments and comparing simulated and experimentally assessed organ
      concentrations. Therefore, the percutaneous, intestinal, or pulmonary absorption
      fraction was estimated based on the blood silver concentration of the respective
      experimental data set. In all of the cases examined, the model could successfully
      predict the biodistribution of ionic silver and 15-150 nm silver nanoparticles,
      which were not coated with substances designed to prolong the circulatory time
      (eg, polyethylene glycol). Furthermore, the results of our model indicate that:
      (1) within the application domain of our model, the particle size and coating had
      a minor influence on the biodistribution; (2) in vivo, it is more likely that
      silver nanoparticles are directly stored as insoluble salt particles than
      dissolve into Ag+; and (3) compartments of the mononuclear phagocytic system play
      a minor role in exposure levels that are relevant for human consumers. We also
      give an example of how the model can be used in exposure and risk assessments
      based on five different exposure scenarios, namely dietary intake, use of three
      separate consumer products, and occupational exposure.

PMID- 24039421
TI  - Inhibited growth of Pseudomonas aeruginosa by dextran- and polyacrylic acid
      coated ceria nanoparticles.
AB  - Ceria (CeO2) nanoparticles have been widely studied for numerous applications,
      but only a few recent studies have investigated their potential applications in
      medicine. Moreover, there have been almost no studies focusing on their possible
      antibacterial properties, despite the fact that such nanoparticles may reduce
      reactive oxygen species. In this study, we coated CeO2 nanoparticles with dextran
      or polyacrylic acid (PAA) because of their enhanced biocompatibility properties,
      minimized toxicity, and reduced clearance by the immune system. For the first
      time, the coated CeO2 nanoparticles were tested in bacterial assays involving
      Pseudomonas aeruginosa, one of the most significant bacteria responsible for
      infecting numerous medical devices. The results showed that CeO2 nanoparticles
      with either coating significantly inhibited the growth of Pseudomonas aeruginosa,
      by up to 55.14%, after 24 hours compared with controls (no particles). The
      inhibition of bacterial growth was concentration dependent. In summary, this
      study revealed, for the first time, that the characterized dextran- and PAA
      coated CeO2 nanoparticles could be potential novel materials for numerous
      antibacterial applications.

PMID- 24039422
TI  - Cell responses without receptors and ligands, using nanosecond pulsed electric
      fields (nsPEFs).

PMID- 24039423
TI  - pH-sensitive degradable nanoparticles for highly efficient intracellular delivery
      of exogenous protein.
AB  - BACKGROUND: Encapsulating exogenous proteins into a nanosized particulate system
      for delivery into cells is a great challenge. To address this issue, we developed
      a novel nanoparticle delivery method that differs from the nanoparticles reported
      to date because its core was composed of cross-linked dextran glassy
      nanoparticles which had pH in endosome-responsive environment and the protein was
      loaded in the core of cross-linked dextran glassy nanoparticles. METHODS: In this
      study, dextran in a poly(ethylene glycol) aqueous two-phase system created a
      different chemical environment in which proteins were encapsulated very
      efficiently (84.3% and 89.6% for enhanced green fluorescent protein and bovine
      serum albumin, respectively) by thermodynamically favored partition. The
      structures of the nanoparticles were confirmed by confocal laser scanning
      microscopy and scanning electron microscopy. RESULTS: The nanoparticles had a
      normal size distribution and a mean diameter of 186 nm. MTT assays showed that
      the nanoparticles were nontoxic up to a concentration of 2000 MUg/mL in human
      hepatocarcinoma cell line SMMC-7721, HeLa, and BRL-3A cells. Of note, confocal
      laser scanning microscopy studies showed that nanoparticles loaded with
      fluorescein isothiocyanate-bovine serum albumin were efficiently delivered and
      released proteins into the cytoplasm of HeLa cells. Flow cytometry and terminal
      deoxynucleotidyl transferase dUTP nick end labeling assays showed that
      nanoparticles with a functional protein (apoptin) efficiently induced significant
      tumor cell apoptosis, which was confirmed by DAPI staining. CONCLUSION: Our
      findings indicate that these nanoparticles meet the high demands for delivering
      protein medicines and have great potential in protein therapy.

PMID- 24039424
TI  - Graphene oxide-reinforced biodegradable genipin-cross-linked chitosan fluorescent
      biocomposite film and its cytocompatibility.
AB  - A genipin-cross-linked chitosan/graphene oxide (GCS/GO) composite film was
      prepared using a solution casting method. Fourier transform infrared (FTIR) and
      ultraviolet-visible (UV-Vis) spectroscopy of the composite films showed that the
      interactions between the CS and oxygen-containing groups of GO resulted in good
      dispersion of the GO sheets in the CS network. The addition of GO decreased the
      expansion ratio of the composite films in physiological conditions and increased
      the resistance to degradation by lysozymes in vitro. As well, the tensile
      strength values of the GCS/GO films were significantly increased with the
      increasing load of GO. Moreover, the GCS/GO composite film also maintained the
      intrinsic fluorescence of GCS. The in vitro cell study results revealed that the
      composite films were suitable for the proliferation and adhesion of mouse
      preosteoblast (MC3T3-E1) cells. The GCS/GO biocomposite films might have a
      potential use in tissue engineering, bioimaging, and drug delivery. 

PMID- 24039425
TI  - Carbon nanoparticles downregulate expression of basic fibroblast growth factor in
      the heart during embryogenesis.
AB  - Carbon nanoparticles, with their high biocompatibility and low toxicity, have
      recently been considered for biomedical applications, including antiangiogenic
      therapy. Critical to normal development and tumor formation, angiogenesis is the
      process of forming capillary blood vessels from preexisting vessels. In the
      present study, we evaluated the effects of diamond and graphite nanoparticles on
      the development of chicken embryos, as well as vascularization of the
      chorioallantoic membrane and heart at the morphological and molecular level.
      Nanoparticles did not affect either body/heart weight or serum indices of the
      embryos' health. However, vascularization of the heart and the density of
      branched vessels were significantly reduced after treatment with diamond
      nanoparticles and, to a lesser extent, graphite nanoparticles. Application of
      nanoparticles significantly downregulated gene and protein expression of the
      proangiogenic basic fibroblast growth factor, indicating that both diamond and
      graphite nanoparticles inhibit angiogenesis. 

PMID- 24039426
TI  - Photothermal ablation of pancreatic cancer cells with hybrid iron-oxide core gold
      shell nanoparticles.
AB  - PURPOSE: Photothermal ablation is a minimally invasive approach, which typically
      involves delivery of photothermal sensitizers to targeted tissues. The purpose of
      our study was to demonstrate that gold nanoparticles are phagocytosed by
      pancreatic cancer cells, thus permitting magnetic resonance imaging (MRI) of
      sensitizer delivery and photothermal ablation. PATIENTS AND METHODS: Iron-oxide
      core/gold-shell nanoparticles (GoldMag(r), 30 nm diameter; Xi'an GoldMag
      Biotechnology Co, Xi'an, People's Republic of China) were used. In a 96-well
      plate, 3 * 104 PANC-1 (human pancreatic cancer cell line) cells were placed.
      GoldMag (0, 25, or 50 MUg/mL) was added to each well and 24 hours allowed for
      cellular uptake. Samples were then divided into two groups: one treated with
      photothermal ablation (7.9 W/cm2) for 5 minutes, the other not treated.
      Photothermal ablation was performed using laser system (BWF5; B&W Tek, Inc,
      Newark, DE, USA). Intraprocedural temperature changes were measured using a fiber
      optic temperature probe (FTP-LN2; Photon Control Inc, Burnaby, BC, Canada). After
      24 hours, the remaining number of viable cells was counted using trypan blue
      staining; cell proliferation percentage was calculated based on the total number
      of viable cells after treatment compared with control. MRI of GoldMag uptake was
      performed using a 7.0T ClinScan system (Bruker BioSpin, Ettlingen, Germany).
      RESULTS: Temperature curves demonstrated that with increased GoldMag uptake,
      laser irradiation produced higher temperature elevations in the corresponding
      samples; temperature elevations of 12.89 degrees C, 35.16 degrees C, and 79.51
      degrees C were achieved for 0, 25, and 50 MUg/mL GoldMag. Without photothermal
      ablation, the cell proliferation percentage changed from 100% to 71.3% and 47.0%
      for cells treated with 25 and 50 MUg/mL GoldMag. Photothermal ablation of PANC-1
      cells demonstrated an effective treatment response, specifically a reduction to
      only 61%, 21.9%, and 2.3% cell proliferation for cells treated with 0, 25, and 50
      MUg/mL GoldMag. MRI was able to visualize GoldMag uptake within PANC-1 cells.
      CONCLUSION: Our findings suggest that photothermal ablation may be effective in
      the treatment of pancreatic cancer. GoldMag nanoparticles could serve as
      photothermal sensitizers, and MRI is feasible to quantify delivery.

PMID- 24039428
TI  - Clozapine reinitiation following a "red result" secondary to chemotherapy.
AB  - We describe a case of a patient whose clozapine was discontinued after a "red
      result" following R-CHOP (rituximab with cyclophosphamide, hydroxydaunorubicin,
      Oncovin, and prednisolone) chemotherapy for large B-cell lymphoma. In some cases,
      manufacturers grant permission, on compassionate grounds, for clozapine to be
      continued or reinitiated following assessment by their consultant hematologist.
      Other than a recent case report, there is not much literature surrounding this
      medical issue. However, since the two leading causes of mortality in
      schizophrenia are cancer and cardiac disease, this is not an uncommon occurrence.
      Clinicians are reluctant to prescribe clozapine in view of its side-effect
      profile, despite its proven efficacy for managing treatment-resistant
      schizophrenia. The alternative is to prescribe two antipsychotics to manage
      symptoms. This approach may be associated with increased side effects, and
      evidence for actual benefits is scant. The consequences were disastrous in this
      case, as the individual not only relapsed following clozapine discontinuation,
      but the therapy for this treatable form of lymphoma had to be delayed. He was
      eventually admitted to an inpatient unit after having been stable for 15 years.
      We managed to stabilize him with olanzapine and aripiprazole which enabled the
      heme-oncology group to resume R-CHOP therapy with filgrastim (granulocyte colony
      stimulating factor). Even so, he continued to exhibit severe psychotic symptoms,
      with religious delusions and auditory hallucinations. We therefore applied for
      permission to rechallenge him on clozapine. Permission was granted when protocol
      conditions were met, and reinitiation went without any adverse events. The
      patient's symptoms showed improvement within a few weeks, and the other
      antipsychotics were discontinued once clozapine was titrated up to 300 mg. The
      decision to reinitiate clozapine following a red result is not to be taken
      lightly, but needs to be considered in terms of the risks versus benefits. More
      literature surrounding this issue would be of great benefit to clinicians,
      patients, and their families. 

PMID- 24039427
TI  - The use of psychotropic medication during pregnancy: how about the newborn?
AB  - Infants are at risk of developing symptoms of Poor Neonatal Adaptation (PNA)
      after exposure to psychotropic drugs in utero. Such symptoms are largely similar
      after exposure to antidepressants, antipsychotics and benzodiazepines and consist
      of mostly mild neurologic, autonomic, respirator and gastro-intestinal
      abnormalities. Most symptoms develop within 48 hours after birth and last for 2-6
      days. After exposure to Selective Serotonin Reuptake Inhibitors (SSRIs),
      mirtazapine or venlafaxine in utero, breastfeeding is presumably protective for
      development of PNA. The dosage of antidepressants does not seem to be related to
      the risk of PNA. In order to objectify possible symptoms of PNA, observation of
      mother and child at the maternity ward is advisable. If PNA symptoms do not
      occur, an observation period of 48-72 hours is sufficient. This applies to all
      types of psychotropic drugs. When PNA symptoms are present it is advisable to
      observe the infant until the symptoms are fully resolved. Observation can be
      performed by trained nurses using the Finnegan scoring list. This observation
      list should be administered every 8 hours. Interpretation of the scores should be
      carried out by a paediatrician. In most cases symptoms are non-specific.
      Therefore other diagnoses, such as infection or neurologic problems, have to be
      excluded. When there is any doubt on possible intoxications during pregnancy,
      toxicological urine screening is indicated. Most cases of PNA are mild, of short
      duration and self-limiting without need for treatment. Supporting measures such
      as frequent small feedings, swaddling and increase of skin to skin contact with
      the mother is usually sufficient. In case of severe PNA it is advised to admit
      the infant to the Neonatal Care Unit (NCU). Phenobarbital is a safe therapeutic
      option. There seem to be no major long term effects; however, additional studies
      are necessary in order to draw definite conclusions. 

PMID- 24039429
TI  - The efficacy and safety of bupropion sustained-release formulation for the
      treatment of major depressive disorder: a multi-center, randomized, double-blind,
      placebo-controlled study in Asian patients.
AB  - This study was conducted to compare the efficacy and safety of bupropion
      sustained-release (SR) formulation orally administered at daily doses of 150
      mg/day (once daily) and 300 mg/day (150 mg twice daily) for 8 weeks versus
      placebo in Asian patients with major depressive disorder. The mean change from
      baseline in Montgomery-Asberg Depression Rating Scale (MADRS) total score at week
      8 was compared between each of the bupropion SR dose groups and the placebo group
      using an analysis of covariance with the multiplicity adjustment by Dunnett's
      step-down procedure. A total of 569 subjects met all of the inclusion criteria
      and proceeded to the treatment phase. The subjects proceeding to the treatment
      phase included 454 Japanese patients and 115 Korean patients. There was no
      statistically significant difference between each of the bupropion SR dose groups
      and the placebo group in the primary efficacy endpoint of change from baseline in
      MADRS total score at week 8. Similar results were generally obtained for all of
      the secondary efficacy endpoints. The secondary analysis and the other subgroup
      analysis did not show a statistically significant difference in efficacy. There
      was no substantial difference in the type, severity, and incidence of adverse
      events (AEs) between the bupropion SR dose groups and the placebo group, which
      indicates a favorable safety profile for bupropion SR. There were no significant
      findings in subjects treated with bupropion SR in regard to sexual dysfunction,
      weight change, and withdrawal syndrome, which are frequently recognized as
      clinical concerns associated with selective serotonin reuptake inhibitors, widely
      used for the treatment of depression. 

PMID- 24039430
TI  - A naturalistic comparison of the efficacy and safety of intramuscular olanzapine
      and intramuscular levomepromazine in agitated elderly patients with
      schizophrenia.
AB  - BACKGROUND: There have not been any reports in Japan clarifying the efficacy and
      safety of intramuscular (IM) olanzapine and IM levomepromazine in agitated
      elderly patients with schizophrenia. This study was a comparative investigation
      of the clinical efficacy and safety of IM olanzapine and IM levomepromazine in
      agitated elderly patients with schizophrenia at 2 hours post-dose. METHODS: The
      subjects were 52 inpatients who were diagnosed with schizophrenia according to
      the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV. Their
      clinical symptoms were assessed using the Positive and Negative Syndrome Scale
      Excited Component (PANSS-EC), PANSS, and Agitation Calmness Evaluation Scale
      (ACES), and their safety was assessed using the Abnormal Involuntary Movement
      Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Drug-Induced Extrapyramidal
      Symptoms Scale (DIEPSS), and glucose test. RESULTS: The PANSS-EC total score, the
      ACES score, and the glucose level significantly decreased from baseline in both
      the IM olanzapine group and the levomepromazine injection group; however, no
      between-group differences were observed. Mean change from baseline in the PANSS
      total score, positive score, the BARS score, and the DIEPSS total score was
      significantly greater in the IM olanzapine injection group compared with the
      levomepromazine injection group. CONCLUSION: The results of this study suggest
      that agitated elderly patients rapidly respond to IM olanzapine and IM
      levomepromazine treatment. Furthermore, these results suggest that IM olanzapine
      is safer than IM levomepromazine and causes greater improvement in positive
      symptoms.

PMID- 24039431
TI  - Comparative study of the influence of diabetes distress and depression on
      treatment adherence in Chinese patients with type 2 diabetes: a cross-sectional
      survey in the People's Republic of China.
AB  - BACKGROUND: The purpose of this study was to explore diabetes-related distress
      and depression and their influence on treatment adherence in Chinese patients
      with type 2 diabetes. METHODS: We surveyed 200 type 2 diabetic patients from two
      public hospitals using the Diabetes Distress Scale (DDS), Zung Self-rating
      Depression Scale, and Revised Treatment Adherence in Diabetes Questionnaire
      (RADQ). A multiple regression model was used to explore the relationship between
      diabetes distress, depression, and treatment adherence. RESULTS: In the 200
      eligible patients, the incidence of depression and diabetes distress was
      approximately 24% and 64%, respectively. The mean score on the RADQ was 23.0 +/-
      6.0. Multiple regression analysis showed that DDS scores (beta = 5.34, P =
      0.000), age (beta = 0.15, P = 0.014), and family history (beta = 3.2, P = 0.016)
      had a positive correlation with depression. DDS scores (beta = -2.30, P = 0.000)
      and treatment methods (beta = -0.93, P = 0.012) were risk factors for poor
      treatment adherence, whereas age (beta = 0.089, P = 0.000) and cohabitation (beta
      = 0.93, P = 0.012) increased treatment adherence. The independent-samples t- test
      showed that depression also affected treatment adherence (t = 2.53, P < 0.05).
      CONCLUSION: These findings suggest that the DDS is a predictor of depression and
      that diabetes distress plays a more important part than depression in treatment
      adherence. Screening for diabetes distress may be useful for primary prevention
      of psychologic problems; however, some form of specialized psychologic
      intervention should be incorporated to promote patient adherence with treatment.

PMID- 24039432
TI  - Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40
      mg and hydrochlorothiazide 12.5/25 mg in daily practice.
AB  - BACKGROUND: The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide
      (HCTZ) as a fixed-dose combination has been investigated in clinical trials
      leading to its approval. The aims of the present study were to confirm these data
      in an unselected patient population in daily practice and to determine the impact
      of physical activity on blood pressure control. METHODS: In a multicenter,
      noninterventional study, 3,333 patients with either insufficient blood pressure
      control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40
      mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the
      fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 +/- 2 weeks.
      Secondary objectives were blood pressure reduction, treatment compliance, and
      impact of physical activity as measured by the sum of weekly energy costs.
      RESULTS: The mean patient age was 63.2 +/- 11.46 years, mean baseline blood
      pressure was 159.6 +/- 15.28/93.5 +/- 9.52 mmHg, and 70.9% had at least one
      additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19),
      and no serious adverse drug reactions occurred. Compliance with drug therapy was
      at least sufficient in more than 99% of patients at the end of the study. Blood
      pressure at the last available visit was reduced by 26.1 +/- 15.5/13.0 +/- 10.1
      mmHg versus baseline (P < 0.0001), but had reduced effectiveness in patients >=75
      years with diabetes or impaired renal function. In 69% of patients, blood
      pressure was normalized (<140/90 mmHg). No noteworthy differences in baseline
      characteristics or baseline blood pressure were found between patients with an
      activity level (sum of weekly energy costs) above or below the median of 9,460.6.
      A higher versus lower physical activity score had no impact on blood pressure
      reduction. CONCLUSION: Our data confirm randomized trial data concerning safe and
      efficient blood pressure reduction using a fixed-dose combination of olmesartan
      40 mg and HCTZ 12.5/25 mg in a large, unselected patient population, independent
      of physical activity level.

PMID- 24039433
TI  - Perceptions of barriers to cardiac rehabilitation use in Brazil.
AB  - Cardiovascular diseases (CVD) are the leading cause of mortality in middle-income
      countries, such as Brazil. However, given the diversity in health care systems in
      Brazil, access to proven services, such as cardiac rehabilitation (CR), varies
      widely. PURPOSE: To describe and compare multilevel barriers to CR enrollment and
      participation in three Brazilian cohorts: (1) cardiac outpatients not attending
      CR (public or private system); (2) cardiac outpatients paying for CR; and (3)
      residents at high-risk of CVD with access to a free comprehensive exercise
      program but not making use of the program. METHODS: Brazilian residents from two
      cities were invited to participate - Florianopolis, an urban center; and Luzerna,
      a rural center. Respondents completed a survey including the Cardiac
      Rehabilitation Barriers Scale. Mann-Whitney U tests were used to compare barriers
      between cohorts cross-sectionally. RESULTS: Six hundred twenty-eight Brazilians
      consented to participate: 237 (37.7%) from Florianopolis, of which 139 (22.1%)
      participated in CR; and 391 (62.3%) from Luzerna. The mean total CR barriers for
      the sample were 1.66 +/- 0.6 and differed significantly by cohort (P < 0.001). CR
      nonattendees from Florianopolis (eg, distance and not knowing about CR) and
      participants from Luzerna (eg, work and family responsibilities) reported
      significantly higher barriers than CR attendees from Florianopolis. CONCLUSION:
      CR nonattendees reported significantly greater barriers than CR attendees. It is
      hoped that the provision of CR will increase, and that the development of the
      programs will be in a manner which mitigates the chief barriers identified
      herein.

PMID- 24039434
TI  - Spanish translation, cross-cultural adaptation, and validation of the
      Questionnaire for Diabetes-Related Foot Disease (Q-DFD).
AB  - PURPOSE: To translate, cross-culturally adapt, and validate the Questionnaire for
      Diabetes-Related Foot Disease (Q-DFD), originally created and validated in
      Australia, for its use in Spanish-speaking patients with diabetes mellitus.
      PATIENTS AND METHODS: The translation and cross-cultural adaptation were based on
      international guidelines. The Spanish version of the survey was applied to a
      community-based (sample A) and a hospital clinic-based sample (samples B and C).
      Samples A and B were used to determine criterion and construct validity comparing
      the survey findings with clinical evaluation and medical records, respectively;
      while sample C was used to determine intra- and inter-rater reliability. RESULTS:
      After completing the rigorous translation process, only four items were
      considered problematic and required a new translation. In total, 127 patients
      were included in the validation study: 76 to determine criterion and construct
      validity and 41 to establish intra- and inter-rater reliability. For an overall
      diagnosis of diabetes-related foot disease, a substantial level of agreement was
      obtained when we compared the Q-DFD with the clinical assessment (kappa 0.77,
      sensitivity 80.4%, specificity 91.5%, positive likelihood ratio [LR+] 9.46,
      negative likelihood ratio [LR-] 0.21); while an almost perfect level of agreement
      was obtained when it was compared with medical records (kappa 0.88, sensitivity
      87%, specificity 97%, LR+ 29.0, LR- 0.13). Survey reliability showed substantial
      levels of agreement, with kappa scores of 0.63 and 0.73 for intra- and inter
      rater reliability, respectively. CONCLUSION: The translated and cross-culturally
      adapted Q-DFD showed good psychometric properties (validity, reproducibility, and
      reliability) that allow its use in Spanish-speaking diabetic populations.

PMID- 24039435
TI  - Using a profile of a modified Brief ICF Core Set for chronic widespread
      musculoskeletal pain with qualifiers for baseline assessment in interdisciplinary
      pain rehabilitation.
AB  - AIM: To describe the use of a "workable" visual profile of function and
      disability, based on a modified Brief International Classification of
      Functioning, Disability and Health (ICF) Core Set for chronic widespread pain,
      for initial assessments in a clinical setting of interdisciplinary pain
      rehabilitation teams. METHOD: The Brief ICF Core Set was slightly adapted to meet
      the needs of an interdisciplinary rehabilitation medicine team working in a
      university outpatient clinic and admitting patients referred from primary care.
      The Core Set categories were made measurable by means of eg, assessment
      instruments and clinical investigations. The resulting profile was given a
      workable shape to facilitate rapid understanding of the initial assessment
      outcome. RESULTS: Individual patients showed different profiles of problems and
      resources, which facilitated individual rehabilitation planning. At the level of
      the study group, the profiles for the Core Set component Body Functions showed
      that most patients had severe impairment in the sensation of pain and exercise
      tolerance categories of function, but most had resources in the motivation and
      memory categories of function. Likewise, for the component Activities, most
      patients had limitations in lifting and carrying objects and remunerative
      employment, but most had resources in intimate relationships and family
      relationships. At first, the use of the modified Brief ICF Core Set in the team
      conference was rather time consuming, but after a couple of months of experience,
      the team assessment took approximately 30 minutes to complete per patient.
      CONCLUSION: The profile of the modified Brief ICF Core Set for chronic widespread
      pain served as a common platform, facilitating cooperation between the
      rehabilitation team members and providing a uniform language, which helped in
      structuring the clinical work. The profile also provided an easily accessible,
      overall view of the patient's problems and resources, which helped in
      understanding the functioning situation of the patient.

PMID- 24039436
TI  - Resilience among caregivers of children with chronic conditions: a concept
      analysis.
AB  - The purpose of this concept analysis is to uncover the essential elements
      involved in caregivers' resilience in the context of caring for children with
      chronic conditions. Walker and Avant's methodology guided the analysis. The study
      includes a literature review of conceptual definitions of caregiver resilience in
      caring for children with chronic conditions. The defining attributes and
      correlates of caregiver resilience are reviewed. Concept analysis findings in a
      review of the nursing and health-related literature show that caregiver
      resilience in the context of caring for chronically ill children can be defined
      within four main dimensions, ie, disposition patterns, situational patterns,
      relational patterns, and cultural patterns. Empiric measurements of the impact of
      caregiver resilience applied to caregivers with children with chronic conditions
      are also reported in the analysis. The findings of this concept analysis could
      help nurses and health care providers to apply the concept of caregiver
      resilience in allied health care and be applied to further studies. 

PMID- 24039438
TI  - Cost-effectiveness of the once-daily efavirenz/emtricitabine/tenofovir tablet
      compared with the once-daily elvitegravir/cobicistat/emtricitabine/tenofovir
      tablet as first-line antiretroviral therapy in HIV-infected adults in the US.
AB  - BACKGROUND: February 2013 US treatment guidelines recommend the once-daily tablet
      of efavirenz/emtricitabine/tenofovir (Atripla(r)) as a preferred regimen and the
      once-daily tablet of elvitegravir/cobicistat/emtricitabine/tenofovir (StribildTM)
      as an alternative regimen for first-line treatment of human immunodeficiency
      virus (HIV). This study assessed the clinical and economic trade-offs involved in
      using Atripla compared with Stribild as first-line antiretroviral therapy in HIV
      infected US adults. METHODS: A Markov cohort model was developed to project
      lifetime health-related outcomes, costs, quality-adjusted life years (QALYs), and
      cost-effectiveness of Stribild compared with Atripla as first-line antiretroviral
      therapy in HIV-1-infected US patients. Patients progressed in 12-week cycles
      through second-line, third-line, and nonsuppressive therapies, acquired immune
      deficiency syndrome, and death. Baseline characteristics and first-line virologic
      suppression, change in CD4 count, and adverse effects (lipid, central nervous
      system, rash, renal) were based on 48-week clinical trial results. These results
      demonstrated equivalent virologic suppression between the two regimens. Point
      estimates for virologic suppression (favoring Stribild) were used in the base
      case, and equivalency was used in the scenario analysis. Published sources and
      expert opinion were used to estimate costs, utilities, risk of acquired immune
      deficiency syndrome, mortality, subsequent-line CD4 count, clinical efficacy, and
      adverse events. Costs were reported in 2012 US dollars. Sensitivity analyses were
      conducted to assess robustness of results. RESULTS: Compared with patients
      initiating Atripla, patients initiating Stribild were estimated to have higher
      lifetime costs. Stribild added 0.041 QALYs over a lifetime at an additional cost
      of $6,886, producing an incremental cost-effectiveness ratio of $166,287/QALY
      gained. Results were most sensitive to first-line response rates, product costs,
      and likelihood of renal adverse events. When equivalent efficacy was assumed,
      Atripla dominated Stribild with lower costs and greater QALYs. CONCLUSION: At a
      societal willingness to pay of $100,000/QALY, Stribild was not cost-effective in
      the base case compared with Atripla for first-line HIV treatment.

PMID- 24039437
TI  - Role of microRNAs in hepatocellular carcinoma: a clinical perspective.
AB  - Hepatocellular carcinoma (HCC) is one of the most deadly tumors, and current
      treatments for the disease are often ineffective. The discovery of the
      involvement of microRNAs (miRNAs) in hepatocarcinogenesis represents an important
      area of investigation for the development of their clinical applications. These
      molecules may act as oncogenes or tumor suppressors by directly or indirectly
      controlling the expression of key proteins involved in cancer-associated
      pathways. On the clinical side, because of their tumor-specific expression and
      stability in tissues and in the circulation, miRNAs have been proposed as novel
      diagnostic tools for classification and prognostic stratification of HCC. In
      recent years, the therapeutic potential of miRNAs has been demonstrated in
      various preclinical studies. Anti-miRNA oligonucleotides and miRNA mimics have
      been found to have antitumor activity. Moreover, by exploiting tumor-specific
      expression of miRNA, efforts have been aimed at improving targeting of tumor
      cells by replicative oncolytic viruses while sparing normal cells. These areas
      are expected to be explored further in the upcoming years to assess the clinical
      value of miRNA-based approaches in HCC and cancer in general. 

PMID- 24039439
TI  - Effects of combination therapy with mitiglinide and voglibose on postprandial
      plasma glucose in patients with type 2 diabetes mellitus.
AB  - Patients with diabetes mellitus are at increased risk from cardiovascular-related
      morbidity and mortality as compared with healthy individuals. An association
      between the postprandial metabolic state and atherogenesis has been observed in
      patients with diabetes mellitus. In the Study to Prevent Non-Insulin-Dependent
      Diabetes Mellitus (STOP-NIDDM), treatment with an alpha-glucosidase inhibitor
      (alpha-GI) in patients with impaired glucose tolerance not only reduced the rate
      of conversion from impaired glucose tolerance to type 2 diabetes mellitus (T2DM),
      but was also associated with a reduction in the risk of cardiovascular events.
      These results suggested the importance of treating postprandial hyperglycemia in
      the early stages of T2DM. Glinides are rapid and short-acting insulin
      secretagogues that bind to the sulfonylurea receptors on pancreatic beta-cells to
      facilitate rapid insulin secretion, restore postprandial early insulin secretion,
      and reduce the postprandial glucose spike. Moreover, alpha-GIs reduce
      postprandial hyperglycemia and insulin secretion by delaying the digestion of
      carbohydrates and polysaccharides in the small intestine. Then, both glinides and
      alpha-GI have beneficial effects for treating patients with T2DM and impaired
      glucose tolerance. Considering the ameliorating effects of these drugs on
      postprandial metabolic disorders, combinations of glinides and alpha-GI might
      constitute a promising therapeutic strategy for managing patients with T2DM, and
      also appear to be suitable for Japanese people, who consume more carbohydrates,
      such as polished rice, than Caucasians. It has recently been reported that
      combined use of mitiglinide and voglibose reduces postprandial insulin secretion
      and blunts diurnal glycemic changes in T2DM patients. This therapy can thus be
      regarded as being suitable for achieving strict postprandial glycemic control. In
      this report, we outline the effects of this combination therapy on postprandial
      plasma glucose and assess its safety. 

PMID- 24039440
TI  - A new Vitreoscilla filiformis extract grown on spa water-enriched medium
      activates endogenous cutaneous antioxidant and antimicrobial defenses through a
      potential Toll-like receptor 2/protein kinase C, zeta transduction pathway.
AB  - Vitreoscilla filiformis (VF) biomass (VFB) has been widely used in cosmetic
      preparations and shown to modulate the major inducible free-radical scavenger
      mitochondrial superoxide dismutase in skin cells. By adding La Roche-Posay (LRP)
      thermal spring water to the VF culture medium, we obtained a biomass (LRP-VFB)
      with a similar mitochondrial superoxide dismutase activation capacity to VF.
      Also, the new biomass more powerfully stimulated mRNA expression and
      antimicrobial peptides in reconstructed epidermis. Interestingly, a predictive
      computer model that analyzed transducing events within skin epidermal cells
      suggested that this protective activity may involve the Toll-like receptor
      2/protein kinase C, zeta transduction pathway. Protein kinase C, zeta inhibition
      was effectively shown to abolish VFB-induced gene stimulation and confirmed this
      hypothesis. This thus opens new avenues for investigation into the improvement of
      skin homeostatic defense in relation to the control of its physiological
      microbiota and innate immunity. 

PMID- 24039441
TI  - Lack of effect of methotrexate in budesonide-refractory collagenous colitis.
AB  - BACKGROUND: In most cases, collagenous colitis can be treated effectively with
      budesonide. However, some patients develop side effects or have chronic symptoms
      refractory to budesonide. This paper reports an open case series of patients
      intolerant or refractory to budesonide who were treated with methotrexate (MTX).
      METHODS AND PATIENTS: Nine patients (seven women) with a median (range) age of 62
      (44-77) years were studied. Bowel movements were registered during 1 week prior
      to baseline and after 6 and 12 weeks' treatment, enabling calculation of the mean
      bowel movements/day. All patients underwent colonoscopy with biopsies before
      inclusion to confirm diagnosis. Open treatment with MTX was given 15 mg
      subcutaneously weekly for 6 weeks and was increased to 25 mg for a further 6
      weeks if symptoms were unresponsive to the first 6 weeks' treatment. The endpoint
      was clinical remission, which was defined as a mean <3 stools/day and mean <1
      watery stool/day/week at Week 12. The Short Health Scale was used at baseline and
      Week 12 to assess health-related quality of life. RESULTS: Five patients
      fulfilled the treatment according to the protocol and four patients discontinued
      the study after 3-6 weeks because of adverse events. No patient achieved clinical
      remission at Week 12. The mean stool frequency/day at baseline was 6.0
      stools/day, thereof 5.4 watery stools/day and after 12 weeks treatment 6.4
      stools/day, thereof 5.7 watery/day. No patient appreciated an improvement of
      health-related quality of life. CONCLUSION: Short-term treatment with MTX had no
      clinical effect in collagenous colitis patients intolerant or refractory to
      budesonide. Alternative therapies should be investigated in these patients.

PMID- 24039442
TI  - Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and
      safety in light of the EXTEND trial.
AB  - The advent of anti-tumor necrosis factor (TNF) therapies revolutionized the
      treatment of inflammatory bowel disease. Adalimumab is a subcutaneous anti-TNF
      agent indicated for use in patients with moderate-to-severe Crohn's disease and
      those with moderate-to-severe ulcerative colitis. In both diseases, it can be
      used for both induction of remission and for maintenance of remission. This
      review focuses on its use in Crohn's disease as described in the EXTEND (Extend
      the Safety and Efficacy of Adalimumab through Endoscopic Healing) trial. Several
      clinical trials using traditional instruments to measure clinical response have
      had endoscopic substudies looking for endoscopic healing. The EXTEND trial is the
      first to use mucosal healing on endoscopy as a primary endpoint for patients with
      moderate-to-severe Crohn's disease and baseline ulcerative disease treated with
      continuous adalimumab. In this well designed trial, the primary endpoint was
      narrowly missed, but the secondary endpoints further the notion that mucosal
      healing should be a more mainstream measure of drug efficacy. How this will
      translate from clinical trials to the clinic is not yet clear, but identifying
      noninvasive markers for mucosal healing, and understanding the implications of
      mucosal healing for safety, resource utilization, and quality of life are all
      worthy targets for further study. The aim of this review is to understand the
      role of mucosal healing, safety profile, and efficacy in patients treated with
      anti-TNF therapy, with particular attention to adalimumab and the EXTEND trial. 

PMID- 24039443
TI  - Gastroparesis: a review of current and emerging treatment options.
AB  - Gastroparesis is a motility disorder of the stomach causing delay in food
      emptying from the stomach without any evidence of mechanical obstruction. The
      majority of cases are idiopathic. Patients need to be diagnosed properly by
      formal testing, and the evaluation of the severity of the gastroparesis may
      assist in guiding therapy. Initially, dietary modifications are encouraged, which
      include frequent and small semisolid-based meals. Promotility medications, like
      erythromycin, and antiemetics, like prochlorperazine, are offered for symptom
      relief. In patients who are refractory to pharmacologic treatment, more invasive
      options, such as intrapyloric botulinum toxin injections, placement of a
      jejunostomy tube, or implantation of a gastric stimulator, can be considered.
      Hemin therapy and gastric electric stimulation are emerging treatment options
      that are still at different stages of research. Regenerative medicine and stem
      cell-based therapies also hold promise for gastroparesis in the near future. 

PMID- 24039444
TI  - Pain management in chronic pancreatitis: taming the beast.
AB  - Abdominal pain is a principal and in many cases, the only observable symptom of
      chronic pancreatitis. Like all chronic pain conditions, managing abdominal pain
      in chronic pancreatitis remains an onerous task for health care providers.
      Different mechanisms have been postulated in trying to better understand the
      pathogenesis of pain in chronic pancreatitis. This review seeks to take a broad
      look at the various options that are available to providers in trying to achieve
      pain relief and a better quality of life for chronic pancreatitis patients. 

PMID- 24039445
TI  - The autonomic nervous system and renal physiology.
AB  - Research in resistant hypertension has again focused on autonomic nervous system
      denervation - 50 years after it had been stopped due to postural hypotension and
      availability of newer drugs. These (ganglionic blockers) drugs have all been
      similarly stopped, due to postural hypotension and yet newer antihypertensive
      agents. Recent demonstration of the feasibility of limited regional transcatheter
      sympathetic denervation has excited clinicians due to potential therapeutic
      implications. Standard use of ambulatory blood pressure recording equipment may
      alter our understanding of the diagnosis, potential treatment strategies, and
      health care outcomes - when faced with patients whose office blood pressure
      remains in the hypertensive range - while under treatment with three
      antihypertensive drugs at the highest tolerable doses, plus a diuretic. We review
      herein clinical relationships between autonomic function, resistant hypertension,
      current treatment strategies, and reflect upon the possibility of changes in our
      approach to resistant hypertension. 

PMID- 24039446
TI  - Test-retest repeatability of strength capacity, aerobic power and pericranial
      tenderness of neck and shoulder muscles in children - relevant for tension-type
      headache.
AB  - BACKGROUND: Frequent or chronic tension-type headache in children is a prevalent
      and debilitating condition for the child, often leading to medication overuse. To
      explore the relationship between physical factors and tension-type headache in
      children, the quality of repeated measures was examined. The aim of the present
      study was to determine the test-retest repeatability of parameters determining
      isometric neck and shoulder strength and stability, aerobic power, and
      pericranial tenderness in children. METHODS: Twenty-five healthy children, 9 to
      18 years of age, participated in test-retest procedures within a 1-week interval.
      A computerized padded force transducer was used for testing. The tests included
      the isometric maximal voluntary contraction and force steadiness of neck flexion
      and extension, and the isometric maximal voluntary contraction and rate of force
      of the dominant shoulder. Pericranial tenderness was recorded by means of
      standardized manual palpation, and a submaximal cycle ergometer test predicted
      maximal oxygen uptake (VO2 max). The measurements were evaluated in steps, using
      the intraclass correlation coefficient (ICC); changes in the mean between the two
      test occasions; the levels of agreement, visualized in Bland-Altman Plots; and by
      quantifying the variability. RESULTS: The results showed an acceptable test
      retest repeatability of isometric maximal voluntary contraction (ICC 0.90-0.97).
      The force steadiness measurements revealed a trend of systematic changes in the
      direction of neck flexion and need further examination in both healthy and ill
      children. The rate of force development, Total Tenderness Score, and prediction
      of VO2 max showed repeatability, with ICC 0.80-0.87. CONCLUSION: The measurements
      of strength capacity, aerobic power, and tenderness provide acceptable
      repeatability, suitable for research in children.

PMID- 24039447
TI  - 3-Phosphoinositide-dependent protein kinase-1 as an emerging target in the
      management of breast cancer.
AB  - It should be noted that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is a
      protein encoded by the PDPK1 gene, which plays a key role in the signaling
      pathways activated by several growth factors and hormones. PDK1 is a crucial
      kinase that functions downstream of phosphoinositide 3-kinase activation and
      activates members of the AGC family of protein kinases, such as protein kinase B
      (Akt), protein kinase C (PKC), p70 ribosomal protein S6 kinases, and serum
      glucocorticoid-dependent kinase, by phosphorylating serine/threonine residues in
      the activation loop. AGC kinases are known to play crucial roles in regulating
      physiological processes relevant to metabolism, growth, proliferation, and
      survival. Changes in the expression and activity of PDK1 and several AGC kinases
      have been linked to human diseases including cancer. Recent data have revealed
      that the alteration of PDK1 is a critical component of oncogenic phosphoinositide
      3-kinase signaling in breast cancer, suggesting that inhibition of PDK1 can
      inhibit breast cancer progression. Indeed, PDK1 is highly expressed in a majority
      of human breast cancer cell lines and both PDK1 protein and messenger ribonucleic
      acid are overexpressed in a majority of human breast cancers. Furthermore,
      overexpression of PDK1 is sufficient to transform mammary epithelial cells. PDK1
      plays an essential role in regulating cell migration, especially in the context
      of phosphatase and tensin homologue deficiency. More importantly, downregulation
      of PDK1 levels inhibits migration and experimental metastasis of human breast
      cancer cells. Thus, targeting PDK1 may be a valuable anticancer strategy that may
      improve the efficacy of chemotherapeutic strategies in breast cancer patients. In
      this review, we summarize the evidence that has been reported to support the idea
      that PDK1 may be a key target in breast cancer management. 

PMID- 24039448
TI  - Perspectives on the immunologic microenvironment of astrocytomas.
AB  - BACKGROUND: The microenvironment of astrocytomas includes infiltrative
      inflammatory cells that are dynamic in nature, possibly reflecting tumor biology.
      We evaluated the inflammatory cell infiltrate in astrocytic tumors aiming for a
      better understanding of their immunobiology. METHODS: Immunohistochemical
      expression of CD68, CD3, and CD20 was investigated in 21 glioblastomas, 21
      anaplastic astrocytomas, 13 diffuse astrocytomas, and 18 pilocytic astrocytomas.
      The inflammatory infiltrate was classified based on microanatomic location as
      perivascular and intratumoral, and subsequently graded semiquantitatively.
      RESULTS: Perivascularly, CD68-positive infiltrate was noted in 71.4% of
      glioblastomas compared with 14.3% of anaplastic astrocytomas (P = 0.0001), 7.7%
      of diffuse astrocytomas (P = 0.0001), and 33.3% of pilocytic astrocytomas (P =
      0.017). Intratumorally, 85.7% of glioblastomas exhibited CD68-positive infiltrate
      compared with 42.9% of anaplastic astrocytomas (P = 0.004), 38.5% of diffuse
      astrocytomas (P = 0.008), and 33.3% of pilocytic astrocytomas (P = 0.001). Among
      diffusely infiltrating astrocytomas, intratumoral CD3-positive infiltrate was
      only associated with glioblastoma. A CD20-positive infiltrate was only detected
      in the perivascular space of a single case of diffuse astrocytoma. CONCLUSION:
      These data indicate a distinct immune profile in the glioblastoma
      microenvironment primarily related to the prevalence of macrophages. Thus, novel
      glioblastoma therapies should address this key CD68-positive population and its
      possible role in generating an antitumor immune response.

PMID- 24039450
TI  - Validity of the Danish National Registry of Patients for chemotherapy reporting
      among colorectal cancer patients is high.
AB  - BACKGROUND: The Danish National Registry of Patients (DNRP) is a potentially
      valuable resource for monitoring national trends in the use of chemotherapy and
      evaluating the benefits and harms of alternative treatments among colorectal
      cancer (CRC) patients in Denmark. However, the validity of chemotherapy reporting
      in the DNRP is unknown. In this study, we evaluated the validity of the DNRP for
      identifying the receipt of chemotherapy and specific treatments, and the timing
      and number of treatments among CRC patients, using medical records and pharmacy
      data as the reference standard. METHODS: We selected a random sample of CRC
      patients with lymph node involvement who were diagnosed at Aarhus University
      Hospital (n = 25) or Aalborg University Hospital (n = 25) from 2009 to 2010.
      Administration dates, specific treatments, and number of treatment courses were
      abstracted for the 180 days post diagnosis from the DNRP, medical records, and
      pharmacy production databases. The prevalence of chemotherapy, timing of first
      administration, and number of courses were described. DNRP data were compared
      with the reference standard for each hospital, and the kappa, sensitivity,
      specificity, positive and negative predictive values, and 95% confidence
      intervals were calculated for the receipt of any chemotherapy and specific
      treatments. RESULTS: The prevalence of chemotherapy was 72% and 68% among CRC
      patients treated in Aarhus and Aalborg, respectively, with >90% of patients
      without distant metastasis receiving treatment within 90 days from diagnosis.
      Patients received on average 4.6 and 4.7 treatment courses in Aarhus and Aalborg,
      respectively. Kappa, sensitivity, and specificity of chemotherapy reporting in
      the DNRP was high (>=0.88), but the sensitivity of individual chemotherapies
      varied by hospital. CONCLUSION: The validity of chemotherapy reporting in the
      DNRP was high, although some variation by hospital exists. The DNRP represents a
      population-based nationwide resource that can be used to provide timely and
      accurate evaluations of chemotherapy use among CRC patients in Denmark.

PMID- 24039451
TI  - Data quality in the Danish National Acute Leukemia Registry: a hematological data
      resource.
AB  - BACKGROUND: The Danish National Acute Leukemia Registry (DNLR) has documented
      coverage of above 98.5%. Less is known about the quality of the recorded data.
      OBJECTIVE: To describe the present coverage of the DNLR, its completeness, and
      accuracy of individual variables for acute myeloid leukemia (AML). Furthermore,
      as a second measure of true coverage of the DNLR, to estimate AML incidence in
      Denmark from DNLR data and compare it to incidence reported from other AML
      registries. PATIENTS AND METHODS: By the end of December 2011, the DNLR
      (established January 2000) included detailed data on a large, well-defined, and
      nonselected Danish population of 2,665 AML patients. We estimated positive
      predictive values (PPVs) and completeness for 30 variables, which included
      patient and disease characteristics, treatment, and treatment outcomes. We
      identified 260 AML patients (10% of all AML patients recorded in the DNLR). We
      used information from medical records as the gold standard. RESULTS: Using the
      Danish National Registry of Patients as a reference, the coverage of the DNLR was
      99.6%. The PPVs of the individual variables ranged from 89.4% to 100%. The
      completeness of individual variables varied between 60.7% and 100%.
      Stratification by time of registration in the DNLR (before 2006 versus 2006 and
      later) revealed higher PPVs and lower frequencies of missing data from 2006. Sex
      adjusted incidence rates were 6.2/100,000 person-years (95% confidence interval
      5.8-6.6) in males and 4.9/100,000 person-years (95% confidence interval 4.5-5.4)
      in females. Yearly incidence rates of AML were higher than the incidence rates
      reported from Sweden (4.5 and 4.2/100,000) and the US (4.5 and 3.1/100,000 in
      Caucasians). CONCLUSION: With few exceptions, there were high values for PPVs and
      completeness of recorded data. Data accuracy and completeness have improved since
      the registry was established. The estimated incidence may indicate that the DNLR
      truly is more complete than other registries. In conclusion, the DNLR is a
      valuable resource for clinical research of AML.

PMID- 24039449
TI  - Critical appraisal of the potential use of cannabinoids in cancer management.
AB  - Cannabinoids have been attracting a great deal of interest as potential
      anticancer agents. Originally derived from the plant Cannabis sativa, there are
      now a number of endo-, phyto- and synthetic cannabinoids available. This review
      summarizes the key literature to date around the actions, antitumor activity, and
      mechanisms of action for this broad range of compounds. Cannabinoids are largely
      defined by an ability to activate the cannabinoid receptors - CB1 or CB2. The
      action of the cannabinoids is very dependent on the exact ligand tested, the
      dose, and the duration of exposure. Some cannabinoids, synthetic or plant
      derived, show potential as therapeutic agents, and evidence across a range of
      cancers and evidence in vitro and in vivo is starting to be accumulated. Studies
      have now been conducted in a wide range of cell lines, including glioma, breast,
      prostate, endothelial, liver, and lung. This work is complemented by an
      increasing body of evidence from in vivo models. However, many of these results
      remain contradictory, an issue that is not currently able to be resolved through
      current knowledge of mechanisms of action. While there is a developing
      understanding of potential mechanisms of action, with the extracellular signal
      regulated kinase pathway emerging as a critical signaling juncture in combination
      with an important role for ceramide and lipid signaling, the relative importance
      of each pathway is yet to be determined. The interplay between the intracellular
      pathways of autophagy versus apoptosis is a recent development that is discussed.
      Overall, there is still a great deal of conflicting evidence around the future
      utility of the cannabinoids, natural or synthetic, as therapeutic agents. 

PMID- 24039452
TI  - Hospitalization rate and 30-day mortality among patients with status asthmaticus
      in Denmark: a 16-year nationwide population-based cohort study.
AB  - OBJECTIVE: Current data on hospitalization and prognosis of acute asthma and
      status asthmaticus are inconclusive. We aim to analyze the rate of first-time
      hospitalizations for status asthmaticus among patients of all ages, the
      proportion admitted to intensive care units (ICU), and the 30-day mortality over
      a 16-year period. METHODS: In this population-based cohort study, we used medical
      registries to identify all first-time status asthmaticus hospitalizations in
      Denmark from 1996 through 2011. Data on comorbidities were also obtained. We
      computed yearly hospitalization rates overall and by gender and age groups, and
      estimated the proportion requiring ICU admission. We estimated 30-day age- and
      gender-standardized mortality. We examined potential misclassification from acute
      exacerbation of chronic obstructive pulmonary disease (COPD) by excluding
      patients with preexisting or concurrent COPD. RESULTS: Of the 5,001 patients
      identified with a first-time status asthmaticus hospitalization, 50.5% were male,
      40.3% were <15 years old, and 12.4% had comorbidity. The hospitalization rate
      increased from 48.0 per 1,000,000 person-years (PY) (95% confidence interval
      [CI]: 45.1-51.1 PY) during 1996-1999 to 70.1 per 1,000,000 PY (95% CI: 66.7-73.7
      PY) during 2008-2011. This may be explained by an increased hospitalization rate
      of children. The standardized 30-day mortality risk declined from 3.3% (95% CI:
      2.5%-4.1%) in 1996-1999 to 1.5% (95% CI: 0.9%-2.1%) in 2008-2011. During 2005
      2011, 10.1% of status asthmaticus patients were admitted to the ICU.
      Hospitalization rates and mortality risk decreased by excluding 939 patients also
      registered with COPD, but overall temporal changes did not change. CONCLUSION:
      From 1996 to 2011, status asthmaticus hospitalization rate increased but remained
      below 100 hospitalizations per 1,000,000 PY. Thirty-day mortality risk was halved
      to less than 2%.

PMID- 24039453
TI  - Nontraumatic dental condition-related visits to emergency departments on
      weekdays, weekends and night hours: findings from the National Hospital
      Ambulatory Medical Care survey.
AB  - OBJECTIVE: To determine whether the rates of nontraumatic dental condition (NTDC)
      related emergency department (ED) visits are higher during the typical working
      hours of dental offices and lower during night hours, as well as the associated
      factors. METHODS: We analyzed data from the National Hospital Ambulatory Medical
      Care Survey for 1997 through 2007 using multivariate binary and polytomous
      logistic regression adjusted for survey design to determine the effect of
      predictors on specified outcome variables. RESULTS: Overall, 4,726 observations
      representing 16.4 million NTDC-related ED visits were identified. Significant
      differences in rates of NTDC-related ED visits were observed with 40%-50% higher
      rates during nonworking hours and 20% higher rates on weekends than the overall
      average rate of 170 visits per hour. Compared with 19-33 year olds, subjects < 18
      years old had significantly higher relative rates of NTDC-related ED visits
      during nonworking hours [relative rate ratio (RRR) = 1.6 to 1.8], whereas those
      aged 73 and older had lower relative rates during nonworking hours (RRR = 0.4;
      overall P = 0.0005). Compared with those having private insurance, Medicaid and
      self-pay patients had significantly lower relative rates of NTDC visits during
      nonworking and night hours (RRR = 0.6 to 0.7, overall P < 0.0003). Patients with
      a dental reason for visit were overrepresented during the night hours (RRR = 1.3;
      overall P = 0.04). CONCLUSION: NTDC-related visits to ED occurred at a higher
      rate during nonworking hours and on weekends and were significantly associated
      with age, patient-stated reason for visit and payer type.

PMID- 24039454
TI  - Knowledge among drug dispensers and antimalarial drug prescribing practices in
      public health facilities in Dar es Salaam.
AB  - BACKGROUND: Irrational prescribing and dispensing of antimalarials has been
      identified as a contributing factor in the emergence of malaria parasites
      resistant to existing antimalarial drugs. Factors that contribute to such
      irrational prescribing and dispensing should therefore be identified to address
      this problem. The aim of this study was to assess irrational antimalarial drug
      dispensing and prescribing practices in public health facilities. METHODS: A
      descriptive-retrospective cross-sectional study was conducted between January and
      June 2011 in order to assess prescribing and dispensing practices for
      antimalarial drugs in three public hospitals and nine health centers in Dar es
      Salaam, Tanzania. Thirty-two drug dispensers were interviewed using a structured
      questionnaire. A total of 4,320 prescriptions for the period January to December
      2010 were collected and assessed for antimalarial drug prescribing patterns.
      RESULTS: The majority (84.6%) of drug dispensers had poor knowledge regarding the
      basic information required from patients before dispensing artemether
      lumefantrine. Seventeen of 32 drug dispensers did not know the basic information
      that should be given to patients in order to increase absorption of artemether
      lumefantrine after oral intake. Most drug dispensers also showed limited
      knowledge about the dosage and contraindications for artemether-lumefantrine.
      Eighty-seven percent of all prescriptions contained artemether-lumefantrine as
      the only antimalarial drug, 77.1% contained at least one analgesic, and 26.9%
      contained at least one antibiotic, indicating unnecessary use of analgesics and
      antibiotics with antimalarial drugs. A substantial number of prescriptions
      contained antimalarial drugs that have already been declared ineffective for the
      treatment of malaria in Tanzania, providing additional evidence of inadequate
      knowledge among health care workers concerning treatment policy. CONCLUSION:
      Despite the government's efforts to increase public awareness regarding use of
      artemether-lumefantrine as first-line treatment for uncomplicated malaria, there
      is still irrational prescribing, dispensing, and use of this combination. Based
      on the results of this study, it is proposed that regular on-the-job training and
      continuing education be provided to drug dispensers and prescribers in public
      health facilities.

PMID- 24039455
TI  - HIV prevalence among the female sex workers in major cities in Myanmar and the
      risk behaviors associated with it.
AB  - BACKGROUND: Myanmar is one of the countries hardest hit by the human
      immunodeficiency virus (HIV) epidemic in Asia. AIM: The objective of the study
      was to determine HIV prevalence among the female sex workers in major cities in
      Myanmar and the risk behaviors associated with it. METHODS: This cross-sectional
      study was conducted among female sex workers in major cities in Myanmar.
      Interviews were conducted by trained research assistants, in private, using a
      questionnaire. The HIV status of the respondents was asked and confirmed by the
      blood test reports from the laboratories of the Myanmar National AIDS Programme
      sexually transmitted infections (STI)/acquired immunodeficiency syndrome (AIDS)
      Teams and nongovernmental organizations (NGOs). RESULTS: There were 200
      respondents in this study. Out of the 136 participants who were tested for HIV,
      25 (18.4%) were HIV-positive. Respondents of other ethnic groups than Myanmars
      and other religions than Buddhist were about six times (odds ratio [OR] 5.9) and
      five times (OR 4.6), respectively, at higher odds of being HIV-positive. Those
      who were earning an income of less than 200,000 kyats were almost three times (OR
      2.9) at higher odds of being HIV-positive. The difference in the age group was
      found to be statistically significant (P = 0.001). Respondents who did not have
      HIV counseling (OR 7.3), who did not use condoms (OR 1.3), and with regular
      partners who refused the use of condoms (OR 6.0) were at higher odds of being HIV
      positive. CONCLUSION: HIV prevention services should include socioeconomic
      support programs, and the clients and regular partners of sex workers should also
      be targeted for behavior-change messages, to reduce condom resistance.

PMID- 24039456
TI  - Agreement between patient-reported and provider-reported choice of contraceptive
      method among family planning patients in New York City: implications for public
      health.
AB  - National data on choice of contraceptive method and subsequent use are critical
      for monitoring progress toward meeting public health goals in reducing unintended
      pregnancy in the US. Yet few studies have focused on the reliability of
      clinically-reported or patient-reported measures of choice of contraceptive
      method for the range of available contraceptive methods. Among 1,844 women
      receiving reproductive health care at two federally funded centers in New York
      City, choice of contraceptive method at the end of the visit from two data
      sources was compared, ie, patient self-report, and provider-report as recorded in
      the clinical-administrative database. Agreement between the two data sources was
      assessed for the sample. Sociodemographic predictors of agreement were assessed
      using logistic regression. Agreement between the data sources was also assessed
      on a method-by-method basis using positive specific agreement. Participants were
      predominantly Latina (69%), foreign-born (76%), and low-income (99% with incomes
      <200% federal poverty level). Agreement of patient-reported and provider-reported
      contraceptive choice was highest for hormonal methods (positive specific
      agreement 94.0%) and intrauterine devices (89.9%), and lowest for condoms
      (53.5%). In the logistic regression model, agreement was lower among teens aged
      16-19 years compared with women aged 25+ years (odds ratio 0.74; 95% confidence
      interval 0.55-0.99). Because teens are more likely to rely on condoms, the
      logistic regression model was repeated, adjusting for provider report of condom
      choice; after adjustment, no sociodemographic differences in agreement were
      observed. National data sources or studies relying on provider-reported method
      choice to derive estimates of contraceptive prevalence may overestimate choice of
      condoms. Our findings raise the question of whether condom choice can be
      accurately assessed by a single open-ended measure of choice of contraceptive
      method. 

PMID- 24039458
TI  - Validation and ease of use of a new pen device for self-administration of
      recombinant human growth hormone: results from a two-center usability study.
AB  - Close adherence to the recommended treatment regimen is important for the success
      of recombinant human growth hormone therapy, although nonadherence can be common.
      Ease of use and safety during use/storage are among several important factors in
      the design of a growth hormone injection device intended for long-term use. This
      study was performed to validate the usability and assess the ease of use of a new
      pen device (SurePalTM) that has been developed to support daily administration of
      the recombinant human growth hormone product, Omnitrope(r) (somatropin). The
      primary objectives of the study were to assess if study participants,
      representing intended users of the pen in clinical practice, were able to perform
      an injection procedure into an injection pad effectively and safely and
      disassemble the pen without receiving a needlestick injury. A total of 106
      participants (61 adults and 45 children/adolescents) were enrolled at two study
      centers (one in the US, one in Germany). Results for both primary usability tasks
      met the predefined acceptance criteria, with >85% of participants successfully
      performing each task. All of the other tasks/handling steps assessed were also
      successfully performed by most participants, with high success rates reflected in
      the high proportion of participants who classified each task as "very easy" or
      "easy". After a second use of the device, 87%-97% of participants rated it as
      "very easy" or "easy" to use. In summary, the new pen device is safe and easy to
      use for both adults and children, and will help to support effective, long-term
      daily administration of the recombinant human growth hormone product,
      Omnitrope(r). 

PMID- 24039457
TI  - Female pattern alopecia: current perspectives.
AB  - Hair loss is a commonly encountered problem in clinical practice, with men
      presenting with a distinctive pattern involving hairline recession and vertex
      balding (Norwood-Hamilton classification) and women exhibiting diffuse hair
      thinning over the crown (increased part width) and sparing of the frontal
      hairline (Ludwig classification). Female pattern hair loss has a strikingly
      overwhelming psychological effect; thus, successful treatments are necessary.
      Difficulty lies in successful treatment interventions, as only two medications -
      minoxidil and finasteride - are approved for the treatment of androgenetic
      alopecia, and these medications offer mediocre results, lack of a permanent cure,
      and potential complications. Hair transplantation is the only current successful
      permanent option, and it requires surgical procedures. Several other medical
      options, such as antiandrogens (eg, spironolactone, oral contraceptives,
      cyproterone, flutamide, dutasteride), prostaglandin analogs (eg, bimatoprost,
      latanoprost), and ketoconazole are reported to be beneficial. Laser and light
      therapies have also become popular despite the lack of a profound benefit.
      Management of expectations is crucial, and the aim of therapy, given the current
      therapeutic options, is to slow or stop disease progression with contentment
      despite patient expectations of permanent hair regrowth. This article reviews
      current perspectives on therapeutic options for female pattern hair loss. 

PMID- 24039459
TI  - Influence of methylphenidate treatment assumptions on cognitive function in
      healthy young adults in a double-blind, placebo-controlled trial.
AB  - BACKGROUND: Increasing numbers of students use stimulants such as methylphenidate
      (MPH) to improve their study capacity, making them prone to subsequent prolonged
      drug abuse. This study explored the cognitive effects of MPH in students who
      either assumed they received MPH or assumed they received a placebo. METHODS: In
      a double-blind, randomized, placebo-controlled trial with a between-subjects
      design, 21 students were subjected to partial sleep deprivation, receiving no
      more than 4 hours sleep the night before they were tested. In the morning, they
      were given either a placebo or 20 mg of MPH. They then performed free recall
      verbal tests and Go/No-Go tasks repeatedly, their moods were evaluated using
      Profile of Mood States and their tiredness was assessed using a visual analog
      scale, with evaluation of vigilance. RESULTS: No significant differences were
      found between those subjects who received MPH and those who received a placebo.
      However, significant differences were found between subjects who assumed they had
      received MPH or had no opinion, and those who assumed they had received a
      placebo. At three minutes, one hour, and one day after memorizing ten lists of 20
      words, those who assumed they had received MPH recalled 54%, 58%, and 54% of the
      words, respectively, whereas those who assumed they had received placebo only
      recalled 35%, 37%, and 34%. CONCLUSION: Healthy, partially sleep-deprived young
      students who assume they have received 20 mg of MPH experience a substantial
      placebo effect that improves consolidation of information into long-term memory.
      This is independent of any pharmacologic effects of MPH, which had no significant
      effects on verbal memory in this study. This information may be used to dissuade
      students from taking stimulants such as MPH during examination periods, thus
      avoiding subsequent abuse and addiction.

PMID- 24039460
TI  - Association of vitamin D deficiency and hyperparathyroidism with anemia: a cross
      sectional study.
AB  - Vitamin D deficiency and anemia are common in the Middle East, and vitamin D
      deficiency and hyperparathyroidism have been reported to be associated with an
      increased prevalence of anemia. In this study, the hypothesis that vitamin D
      deficiency and hyperparathyroidism may be associated with anemia in a Bahraini
      population was tested. Association of hyperparathyroidism and vitamin D levels
      (deficiency and insufficiency) with anemia was investigated in 421 Bahrainis (213
      males and 208 females). In females, the prevalence of anemia was significantly
      associated with vitamin D deficiency independent of parathyroid hormone levels
      (odds ratio: 2.9; 95% confidence interval: 2.3-10.5; P = 0.001). In females, the
      prevalence of anemia appeared to be significantly associated with
      hyperparathyroidism (odds ratio: 2.1; 95% confidence interval: 1.2-3.7; P =
      0.01); however, this significant association disappeared when adjusted for
      vitamin D deficiency (odds ratio: 1.6; 95% confidence interval: 0.75-6.5; P =
      0.154). Results from this study suggest that vitamin D deficiency is
      independently associated with anemia in females but not males. Further studies to
      determine whether vitamin D supplementation could be used to treat anemia are
      warranted. 

PMID- 24039461
TI  - Information-theoretic model-averaged benchmark dose analysis in environmental
      risk assessment.
AB  - An important objective in environmental risk assessment is estimation of minimum
      exposure levels, called Benchmark Doses (BMDs), that induce a pre-specified
      Benchmark Response (BMR) in a dose-response experiment. In such settings,
      representations of the risk are traditionally based on a specified parametric
      model. It is a well-known concern, however, that existing parametric estimation
      techniques are sensitive to the form employed for modeling the dose response. If
      the chosen parametric model is in fact misspecified, this can lead to inaccurate
      low-dose inferences. Indeed, avoiding the impact of model selection was one early
      motivating issue behind development of the BMD technology. Here, we apply a
      frequentist model averaging approach for estimating benchmark doses, based on
      information-theoretic weights. We explore how the strategy can be used to build
      one-sided lower confidence limits on the BMD, and we study the confidence limits'
      small-sample properties via a simulation study. An example from environmental
      carcinogenicity testing illustrates the calculations. It is seen that application
      of this information-theoretic, model averaging methodology to benchmark analysis
      can improve environmental health planning and risk regulation when dealing with
      low-level exposures to hazardous agents.

PMID- 24039462
TI  - Cordyceps bassiana and Production of Stromata in vitro Showing Beauveria Anamorph
      in Korea.
AB  - A Cordyceps species was found with a Beauveria anamorph state on larval insect
      cadavers on Obong mountains in Gangwon Provinces, Republic of Korea. Cultures
      from discharged ascospores formed an anamorph identifiable as Beauveria bassiana.
      This teleomorph-anamorph connection was also confirmed by the in vitro production
      of fertile ascomata from conidial cultures with morphology like that of field
      collected specimen. This is the first report of in vitro production of a
      teleomorph for any Beauveria species. The Cordyceps species has been conspecified
      as Cordyceps bassiana, a species described from China with B. bassiana anamorph. 

PMID- 24039463
TI  - Molecular identification of arbuscular mycorrhizal fungal spores collected in
      Korea.
AB  - Arbuscular mycorrhizas (AM) have mutualistic symbiosis with plants and thus
      efforts have been placed on application of these symbiotic relationships to
      agricultural and environmental fields. In this study, AM fungi were collected
      from 25 sites growing with 16 host plant species in Korea and cultured with
      Sorghum bicolor in greenhouse condition. AM fungal spores were extracted and
      identified using both morphological and molecular methods. Using morphological
      characters, total 15 morpho-speices were identified. DNA was extracted from
      single spore of AM fungi and a partial region on 18S rDNA was amplified using
      nested PCR with AM fungal specific primers AML1/AML2. A total of 36 18S rDNA
      sequences were analyzed for phylogenetic analysis and 15 groups of AM fungi were
      identified using both morphological and molecular data of spores. Among the
      species, 4 species, Archaeospora leptoticha, Scutellospora castanea, S.
      cerradensis, S. weresubiae were described for the first time in Korea and two
      species in Glomus and a species in Gigaspora were not identified. Morphological
      and molecular identification of AM fungal spores in this study would help
      identify AM fungal community colonizing roots. 

PMID- 24039464
TI  - Bioconversion of Straw into Improved Fodder: Preliminary Treatment of Rice Straw
      Using Mechanical, Chemical and/or Gamma Irradiation.
AB  - Crude protein (CP) content of mechanically ground rice straw into small particles
      by an electric grinder and reducing value (RV) and soluble protein (SP) in the
      culture filtrate were lower than that of the chopped straw into 5~6 cm lengths
      when both ground and chopped straws were fermented with Aspergillus ochraceus, A.
      terreus or Trichoderma koningii, at steady conditions. The reduction rate of RV,
      SP and CP was 22.2, 2.4, 7.3%; 9.1, 4.9, 8.5% or 0.0, 0.0, 3.6% for the three
      fungi, respectively. Chemical pretreatment of straw by soaking in NH4OH for a day
      caused significant increase in CP of the fermented straw than the other alkali
      and acidic pretreatments. Gamma irradiation pretreatment of dry and wet straw
      with water, specially at higher doses, 100, 200 or 500 kGy, caused significant
      increase in RV and SP as CP in the fermented straw by any of these fungi.
      Chemical-physical combination pretreatment of rice straw reduced the applied dose
      of gamma irradiation required for increasing fermentable ability of fungi from
      500 kGy to 10 kGy with approximately the same results. Significant increases in
      RV and SP of fermented straw generally occurred as the dose of gamma irradiation
      for pretreated straw, which combined with NH4OH, gradually rose. Whereas, the
      increase percentage in CP of fermented straw that was pretreated by NH4OH-10 kGy
      was 12.4%, 15.4% or 8.6% for A. ochraceus, A. terreus or T. koningii,
      respectively. 

PMID- 24039465
TI  - Production of gluconic Acid by some local fungi.
AB  - Forty-one fungal species belonging to 15 fungal genera isolated from Egyptian
      soil and sugar cane waste samples were tested for their capacity of producing
      acidity and gluconic acid. For the tests, the fungi were grown on glucose
      substrate and culture filtrates were examined using paper chromatography
      analysis. Most of the tested fungi have a relative wide potentiality for total
      acid production in their filtrates. Nearly 51% of them showed their ability of
      producing gluconic acid. Aspergillus niger was distinguishable from other species
      by its capacity to produce substantial amounts of gluconic acid when it was
      cultivated on a selective medium. The optimized cultural conditions for gluconic
      acid yields were using submerged culture at 30C at initial pH 6.0 for 7 days of
      incubation. Among the various concentrations of substrate used, glucose (14%,
      w/v) was found to be the most suitable carbon source for maximal gluconic acid
      during fermentation. Maximum values of fungal biomass (10.02 g/l) and gluconic
      acid (58.46 g/l) were obtained when the fungus was grown with 1% peptone as sole
      nitrogen source. Influence of the concentration of some inorganic salts as well
      as the rate of aeration on the gluconic acid and biomass production is also
      described. 

PMID- 24039466
TI  - The Fruiting Body Formation of Oudemansiella radicata in the Sawdust of Oak
      (Quercus variabilis) Mixed with Rice Bran.
AB  - To screen additives and their mixed ratio suitable for the mycelial growth and
      fruiting body formation of Oudemansiella radicata in the oak sawdust, additives
      such as rice bran, fermented soybean powder and wheat bran were used. Generally,
      the mycelial growth of O. radicata has been stable on oak sawdust mixed with rice
      bran of 5~20%. In case that O. radicata was cultured for about 30 days at 22 +/-
      1C under the illumination (350 lux) of 12 hours and moisture condition of 90 +/-
      5%, the primordia have been formed gradually from red-brown crusts covering the
      surface of oak sawdust media. Based on the experimental results from 9 strains of
      O. radicata, fruiting bodies were produced widely on oak sawdust medium mixed
      with rice bran of 5 to 30%. Even though fruiting bodies of O. radicata have been
      produced well on oak sawdust media mixed with rice bran, fruiting bodies of O.
      radicata were produced intensively on oak sawdust media mixed with rice bran of
      10%. Therefore, this result will provide a basic information for commercial
      production of fruiting body of wild O. radicata. This result is the first report
      associated with an artificial fruiting body formation of O. radicata in Korea. 

PMID- 24039467
TI  - Effects of interspecific interactions of arbuscular mycorrhizal fungi on growth
      of soybean and corn.
AB  - Growth responses of Zea mays and Glycine max to colonization by mixture of
      combination of three species of arbuscular mycorrhizal (AM) fungi, two species of
      Glomus and a species of Scutellospora were compared. In Zea mays, plants
      inoculated with single species of AM fungi showed significantly higher in dry
      weight than non-mycorrhizal plant for all three AM fungal species. Also, growth
      of plants inoculated with spores of two species of AM fungi was significantly
      higher than nonmycorrhizal control except for plants inoculated with two Glomus
      species. When three species of AM fungi were inoculated, the plants showed the
      highest growth. In Glycine max, plants with single AM fungal species inoculation
      were not significantly different in plant growth from nonmycorrhizal plants. When
      the plants were inoculated with combination of two or more AM fungal species,
      their growth significantly increased compared to nonmycorrhizal plants. In both
      plant species, mycorrhizal root colonization by Scutellospora species was
      significantly lower than by Glomus species. 

PMID- 24039468
TI  - Diaporthin and Orthosporin from the Fruiting Body of Daldinia concentrica.
AB  - In our continuing study on the chemical constituents in the fruiting bodies of
      Daldinia concentrica, diaporthin and orthosporin were isolated. Their chemical
      structures were assigned based on various spectral studies. Diaporthin and
      orthosporin, phytotoxins previously found in Aspergillus ochraceus, were isolated
      from wood-rotting mushroom D. concentrica for the first time. 

PMID- 24039469
TI  - Notes on two species of the laboulbeniales from tibet.
AB  - Two species of the Laboubeniales based on the Tibetan collections are described.
      They are new to the mycological flora of Tibet. Laboulbenia polyphaga found on
      several parts of Amara majuscula was characterized by having the outer appendages
      not ramified and simple. Peyritschiella protea obtained on the lower abdomen of
      Philonthus wuesthoffi, had two perithecia and two antheridia produced on the
      third layer of receptacle. 

PMID- 24039470
TI  - Comparison of RAPD, AFLP, and EF-1alpha Sequences for the Phylogenetic Analysis
      of Fusarium oxysporum and Its formae speciales in Korea.
AB  - Although Fursarium oxysporum causes diseases in economically important plant
      hosts, identification of F. oxysporum formae speciales has been difficult due to
      confusing phenotypic classification systems. To resolve these complexity, we
      evaluated genetic relationship of nine formae speciales of F. oxysporum with
      random amplified polymorphic DNA (RAPD), amplified fragment length polymorphism
      (AFLP), and translation elongation factor-1 alpha (EF-1alpha) gene. In addition,
      the correlation between mycotoxin content of fusaric acid and isolates based on
      molecular marker data was evaluated using the modified Mantel's test. According
      to these result, these fusaric acid-producing strains could not identify clearly,
      and independent of geographic locations and host specificities. However, in the
      identification of F. oxysporum formae speciales, especially, AFLP analysis showed
      a higher discriminatory power than that of a the RAPD and EF-1alpha analyses, all
      three techniques were able to detect genetic variability among F. oxysporum
      formae speciales in this study. 

PMID- 24039471
TI  - Some unrecorded higher fungi of the seoraksan and odaesan national parks.
AB  - Higher Fungi were collected twice a month from May to September 2004 during field
      survey trips to Seoraksan and Odaesan National Parks. All the collected specimens
      were investigated for the morphological characters of carpophores and other
      features, and deposited in the herbarium of the Entomopathogenic Fungal Culture
      Collection (EFCC), Kangwon National University, Chuncheon. Among the identified
      specimens, three genera Rhodotus, Hotermannia and Sebacina and four species
      Rhodotus palmatus, Gomphus clavatus, Holtermannia corniformis and Sebacina
      incrustans were confirmed as new to Korea and reported here with descriptions. 

PMID- 24039472
TI  - Characteristics of Hypovirulent Strains of Chestnut Blight Fungus, Cryphonectria
      parasitica, Isolated in Korea.
AB  - Chestnut blight disease caused by Cryphonectria parasitica is widely distributed
      throughout chestnut tree plantations in Korea. We surveyed 65 sites located at 9
      provinces in South Korea, and isolated 248 virulent and 3 hypovirulent strains of
      chestnut blight fungus. Hypovirulent strains had dsRNA virus in the cytoplasm,
      which is one of the typical characteristics of hypovirulent strains. In addition,
      they showed more characteristics of hypovirulent strains, i.e., suppressed
      conidiation, reduced pigmentation in colony color, and reduced phenol oxidase
      activity as well as reduced pathogenicity. Hypovirulent strains, KCPH-22, KCPH
      135 and KCPH-136, had a genomic dsRNA band with the molecular weight of 12.7 kb,
      which is the L-dsRNA of CHV1. They also had a 2.7 kb defective dsRNA band. Single
      conidia isolated from hypovirulent strains were cultured and various phenotypes
      and absence of dsRNA bands were obtained from single conidial cultures, which
      means that hypovirulence transmission is unstable in asexual reproduction and
      variations in viral heredity by asexual reproduction. Biocontrol trial using
      hypovirulent strains was also carried out in the chestnut tree plantations, and
      canker expansion in the treated trees was stopped and healed by callus formation
      at the margin of the canker. These results show the potentials in successful
      biocontrol of chestnut blight if the vegetatively compatible hypovirulent strains
      could be directly used around the canker formed by compatible virulent strains. 

PMID- 24039473
TI  - Resistance Induction and Enhanced Tuber Production by Pre-inoculation with
      Bacterial Strains in Potato Plants against Phytophthora infestans.
AB  - Efficacy of resistance induction by the bacterial isolates Pseudomonas putida
      (TRL2-3), Micrococcus luteus (TRK2-2) and Flexibacteraceae bacterium (MRL412),
      which were isolated from the rhizosphere of plants growing in Jeju Mountain, were
      tested in a greenhouse. The disease severity caused by Phytophthora infestans was
      effectively reduced in the potato plants pre-inoculated with bacterial isolates
      compared with those of the untreated control plants growing in a greenhouse. In
      order to estimate the level of protection by the bacterial isolates, Mancozeb WP
      (Diesen M(r), Kyong nong) and DL-3-amino butyric acid (BABA) were pre-treated,
      whereas Dimethomorph WP (Forum(r), Kyong nong) and phosphonic acid (H3PO3) were
      post-treated the challenge inoculation with the pathogen. Disease severities of
      chemical pre-treated as well as post-treated plants were reduced compare to those
      of the untreated. The disease reduction in the plants pre-treated with Mancozeb
      WP was the highest, whereas that of post-treated with Dimethomorph WP was the
      lowest. The yields of plants pre-inoculated with three bacterial isolates were
      greatly increased than those of control plants. These results suggest that
      biological control by bacterial isolates might be an alternative strategy against
      late blight disease in potato plants growing in greenhouse. 

PMID- 24039474
TI  - Isolation, Regeneration and PEG-Induced Fusion of Protoplasts of Pleurotus
      pulmonarius and Pleurotus florida.
AB  - Inter-specific hybridization between Pleurotus pulmonarius and P. florida was
      attempted through PEG-induced protoplast fusion to select a fusant. The protocol
      for protoplast release, regeneration and fusion in these two Pleurotus species
      was standardized using the variables controlling the process. The mixture of
      mycolytic enzymes, i.e. commercial cellulase, crude chitinase and pectinase, KCl
      (0.6 M) as osmotic stabilizer, pH 6 of the phosphate buffer and an incubation
      time of 3 hours resulted in the maximum release of protoplasts from 3-day-old
      mycelia of P. florida (5.3~5.75 * 10(7) protoplasts/g) and P. pulmonarius (5.6~6
      * 10(7) protoplasts/g). The isolated protoplasts of P. florida regenerated
      mycelium with 3.3% regeneration efficiency while P. pulmonarius showed 4.1%
      efficiency of regeneration. Polyethyleneglycol (PEG) - induced fusion of
      protoplasts of these two species resulted in 0.28% fusion frequency. The fusant
      produced fruiting bodies on paddy straw but required a lower temperature of crop
      running (24 +/- 2C) than its parents which could fruit at 28 +/- 2C. The stable
      fusant strain was selected by testing for the selected biochemical markers i.e.
      Carbendazim tolerance and utilization of the lignin degradation product,
      vanillin. 

PMID- 24039475
TI  - Seed Germination of Gastrodia elata Using Symbiotic Fungi, Mycena osmundicola.
AB  - The germination rate and longevity of seeds of Gastrodia elata Blume have been
      observed for 48 weeks using Mycena osmundicola strain H-21, one of fungi
      stimulating seed germination. Storage condition of post-harvest seeds was
      observed in the different temperature ranges of -30C, -5C, 5C and 30C for 48
      weeks. After storage period of 48 weeks, the germination rate of G. elata was
      65.7% at 5C and 71.6% at -5C, respectively. Although the germination rate of G.
      elata was 77.3% for 11 weeks at 25C, the germination rate had been decreased
      gradually to 49.3% at 13 weeks, 0.3% at 23 weeks and then 0% at 25 weeks. The
      germination rate was reached to the level of 10% for 2 weeks at -30C and then
      decreased to 0%. 

PMID- 24039476
TI  - Observations on Some of the Mycelial Growth and Pigmentation Characteristics of
      Cordyceps militaris Isolates.
AB  - Characteristic growth patterns of Cordyceps militaris isolates on various media,
      under varying light conditions and at varying incubation periods were examined.
      Light was found to be the most critical single factor in determining the density,
      texture, and pigmentation of the mycelial culture of the fungus. However, under
      the light condition, the degree of pigmentation and mycelial density were found
      to be affected by the incubation period and type of medium. Irrespective of the
      variations in medium type or incubation period, there was no pigmentation of the
      mycelium under dark condition. Radial growth of the mycelium was faster under
      dark incubation rather than under light incubation. Abundant mycelial density and
      darkest pigmentation of C. militaris isolates were produced in nutritionally rich
      media like SDAY, SMAY and CZYA, suggesting that these media may fulfill all the
      requirements for vegetative growth of the fungus. Growth characteristics of C.
      militaris isolates could be easily observed by the simple agar culture method,
      which would be useful to characterize the phenotypic characteristics of large
      number of pure cultures of the fungus under given conditions of growth factors
      such as medium, light and temperature. 

PMID- 24039477
TI  - Inhibitory Effects of Na-Hypochlorite and Heating on the Mycobiota Associated
      with Fruits or Juice of Passion (Passiflora edulis Sims) in Uganda.
AB  - A total of 34 species belonging to 21 genera of fungi were recorded on passion
      fruits of both pure and hybrid origin in Uganda, however, the pure type exhibited
      wider spectrum (28 species and 16 genera) than the hybrid type (21 & 15). Also,
      yeasts (unidentified and Rhodotorula mucilaginosa) were also encountered in high
      numbers. Moreover, the mean count of all mycobiota obtained from the pure type
      was higher than that of hybrid, despite the bigger size of the later. Members of
      yeasts and Cladosporium followed by Phoma, Penicillium, Fusarium and Alternaria
      species dominated on passion fruits of pure origin, while only C.
      cladosporioides, F. solani and yeasts dominated on the hybrid type. Treatment
      with Na-hypochlorite exhibited inhibitory effects on the total mycobiotic
      propagules as well as the dominant species from fruits of both types. The current
      results, therefore, suggest the use of Na-hypochlorite to control the post
      harvest mycobiota associated with passion fruits. Regarding the mycobiota
      contaminating passion juice, yeasts were found to be the major contaminants with
      Candida parapsilosis being the most common. Moulds constituted only a minor
      proportion with Acremonium strictum followed by Fusarium chlamydosporum, F.
      moniliforme, F. acuminatum and F. solani as the most dominant species. In the
      heat-treated juice samples, the counts of the most commonly encountered mycobiota
      (both yeasts and molds) were significantly inhibited or completely eliminated.
      Some unidentified Bacillus species were also recovered from the juice, however,
      their counts in the heated samples were increased but insignificantly. 

PMID- 24039478
TI  - Variation in Sensitivity Among Some Isolates of Macrophomina phaseolina Isolated
      from Cotton Roots to Flutolanil Fungicide.
AB  - Toxicity of the fungicide Flutolanil was in vitro tested against 20 isolates of
      Macrophomina phaseolina and cotton seedlings of ten commercial cotton cultivars.
      The isolates were recovered from roots of cotton plants obtained from different
      cotton-growing areas in Egypt. Most of the tested isolates were sensitive to
      Flutolanil; however, they varied in sensitivity. Twenty-five percent of the
      isolates were highly sensitive where IC50 ranged from < 1 to 5.1 ug/ml, 20% of
      the isolates were sensitive where IC50 ranged from 15 to 30 ug/ml, 45% of the
      isolates were moderately sensitive where IC50 ranged from 46 to 58.5 ug/ml, and
      10% of the isolates were not much sensitive (tolerant) where IC50 was > 100
      ug/ml. Flutolanil was very safe on both shoots and roots of the tested cultivars
      (IC50 > 100 ug/ml). Treating cotton seeds with Flutolanil resulted in highly
      significant (P < 0.01) reductions in pathogenicity of 18 isolates and a
      significant reduction (P < 0.05) in pathogenicity of isolate M29. M1 was the only
      isolate, which was insensitive to the application of Flutolanil. In vivo toxicity
      to Flutolanil was not correlated with its in vitro toxicity. However, a highly
      significant correlation (r = 0.60, P < 0.01) was observed between pathogenicity
      of isolates and the in vivo toxicity of the fungicide. 

PMID- 24039479
TI  - Agrobacterium-mediated Transformation of the Winter Mushroom, Flammulina
      velutipes.
AB  - Flammulina velutipes was transformed efficiently by Agrobacterium-mediated
      transformation system. The transformation frequency was about 16% with the gill
      tissues of the fungal fruiting body. Southern hybridization and genetic analysis
      suggest that the introduced DNA was inserted onto different locations of the
      fungal genome, and inherited stably to the next generation via basidiospores.
      Transformation or gene tagging with Agrobacterium T-DNA based vector should be
      useful for wide ranges of genetic or molecular biological studies of the
      mushroom. 

PMID- 24039480
TI  - Detection of Cellulolytic Activity in Ophiostoma and Leptographium species by
      Chromogenic Reaction.
AB  - To understand the ability of producing cellulolytic enzyme activity in the
      sapstaining fungi, four species of Ophiostoma and two species of Leptographium
      were investigated in the culture media containing each of cellulose substrates
      such as CM-cellulose, Avicel and D-cellobiose and each of chromogenic dyes such
      as Congo-Red, Phenol Red, Remazol Brilliant Blue and Tryphan Blue. When the fungi
      were grown for 5~7 days at 25C, the formation of clear zone by chromogenic
      reaction around the margin of the fungal colony was demonstrated in all the
      culture media Congo-Red containing CM-cellulose. There was difference in the
      formation of clear zone among the dyes. Only Ophiostoma setosum and Leptographium
      spp. showed cellulolytic activity to the three substrates. Overall, the results
      of this study show that ophiostomatoid sapstaining fungi can produce cellulolytic
      enzymes. 

PMID- 24039481
TI  - Two new species of trichoderma associated with green mold of oyster mushroom
      cultivation in Korea.
AB  - This paper describes and illustrates two new species, Trichoderma pleurotum and
      T. pleuroticola, associated with green mold disease of oyster mushroom in Korea. 

PMID- 24039482
TI  - Variation in Biochemical Composition among Indian Isolates of Sclerotinia
      sclerotiorum.
AB  - Biochemical variability among 20 Indian isolates of Sclerotinia sclerotiorum
      collected from different hosts/soil samples from different localities in India is
      reported. High Performance Liquid Chromatographic (HPLC) analysis of ethyl
      acetate fraction of culture filtrate, mycelia, sclerotia and sclerotial exudate
      showed 15~23 peaks but only 11 could be identified. They were tannic, gallic,
      oxalic, caffeic, vanillic, ferulic, O-coumeric, chlorogenic, cinnamic, salicylic
      and gentisic acids. The amount of phenolic compounds varied among the culture
      filtrates, mycelia, sclerotia and sclerotial exudates of S. sclerotiorum. 

PMID- 24039483
TI  - Antifungal Activity of a Phytoterpenoid (AOS-A) Isolated from Artabotrytis
      odoratissimus on Spore Germination of Some Fungi.
AB  - Phytoterpenoid isolated from Artabotrytis odoratissimus inhibited spore
      germination of some plant pathogenic as well as saprophytic fungi e.g. Alternaria
      alternata, A. solani, Cercospora sp., Curvularia maculans, C. pennisetti,
      Fusarium udum, Helminthosporium echinochlova, H. frumentacie, H. penniseti and
      Ustilago cynodontis. In Curvularia maculans and H. frumentacie, spore germination
      was completely inhibited at 2000 ppm. However, Curvularia maculans and C.
      pennisetti showed considerable sensitivity to this chemical even at 500 ppm. 

PMID- 24039484
TI  - Antioxidative Activity of Lichen Thamnolia vermicularis in vitro.
AB  - This study was aimed at evaluating the antioxidant activities of methanol extract
      of Thamnolia vermicularis. The antioxidant activity, reducing power, superoxide
      anion radical scavenging and free radical scavenging activities were studied. The
      antioxidant activity of the extract correlated with its concentration (0.2~2
      mg/ml) in the reaction mixtures containing linoleic acid. Upto 67% of lipid
      peroxidation was inhibited by 2 mg/ml of the lichen extract. The extract showed
      strong free radical scavenging activity similar to that of BHA (positive control)
      in a manner of concentration dependent. The lichen extract also showed moderate
      effects on superoxide anoin scavenging activity and reducing power, which was not
      so effective as that of Quercetin and BHA used as positive controls. This study
      suggests that T. vermicularis lichen can be used as a novel source of natural
      antioxidant. 

PMID- 24039485
TI  - Raw starch degrading amylase production by various fungal cultures grown on
      cassava waste.
AB  - The solid waste of sago industry using cassava was fermented by Aspergillus
      niger, Aspergillus terreus and Rhizopus stolonifer in solid state fermentation.
      Cassava waste contained 52 per cent starch and 2.9 per cent protein by dry
      weight. The amylase activity was maintained at a high level and the highest
      amylase activity was observed on the 8(th) day in R. stolonifer mediated
      fermentation. R. stolonifer was more efficient than Aspergillus niger and
      Aspergillus terreus in bioconverting cassava waste into fungal protein (90.24
      mg/g) by saccharifying 70% starch and releasing 44.5% reducing sugars in eight
      days of solid state fermentation. 

PMID- 24039486
TI  - Selection of Superior Strains of Cordyceps militaris with Enhanced Fruiting Body
      Productivity.
AB  - In vitro fruiting bodies were produced from ten different isolates of Cordyceps
      militaris EFCC C-5736, EFCC C-5941, EFCC C-5976, EFCC C-6040, EFCC C-6849, EFCC C
      7268, EFCC C-7342, EFCC C-7992, EFCC C-8027 and EFCC C-8549. Single ascospores
      were isolated from in vitro grown fruiting bodies and used for fruiting body
      production in brown rice medium by both intra-strain crossing and out-crossing.
      Length and dry wt. of stromata grown in vitro were measured. Strains producing
      highest dry wt. of stromata were selected. Both intra-strain crossings and inter
      strain crossings of single ascospore strains were found to produce profuse
      fruiting bodies of C. militaris. 

PMID- 24039487
TI  - Screening of Cyanobacteria (Blue-Green algae) from Rice Paddy Soil for Antifungal
      Activity against Plant Pathogenic Fungi.
AB  - Soil cyanobacteria isolated from the rice paddy fields of 10 different locations
      across Korea were evaluated by agar plate diffusion test for antifungal activity.
      Aqueous, petroleum ether, and methanol extracts from one hundred and forty two
      cyanobacterial strains belonging to the 14 genera were examined for antifungal
      properties against seven phytopathogenic fungi causing diseases in hot pepper
      (Capsicum annuum L). Of total cyanobacteria, nine cyanobacteria (6.34%) exhibited
      antifungal effects. The nine cyanobacteria selected with positive antifungal
      activities were two species of Oscillatoria, two of Anabaena, three of Nostoc,
      one of Nodularia, and one of Calothrix. Alternaria alternata and Botrytis cinerea
      were inhibited by nine and eight species of cyanobacteria, respectively. Rhizopus
      stolonifer was suppressed by only methanol extract of Nostoc commune FK-103. In
      particular, Nostoc commune FK-103 and Oscillatoria tenuis FK-109 showed strong
      antifungal activities against Phytophthora capsici. Their antifungal activity at
      the late exponential growth phase is related to the growth temperature and not
      associated with the growth parameters such as cell biomass and chlorophyll-alpha
      concentration. The high inhibition levels of antibiotics were 22.5 and 31.8 mm
      for N. commune FK-103 and O. tenuis FK-109, respectively. The optimal temperature
      for antibiotic productivity was 35C. 

PMID- 24039488
TI  - Mycelial Extract of Phellinus linteus Induces Cell Death in A549 Lung Cancer
      Cells and Elevation of Nitric Oxide in Raw 264.7 Macrophage Cells.
AB  - In the present study, in order to investigate the anti-proliferative phenomenon
      of PLME, the effects of mycelial extract of Phellinus linteus (PLME) on the
      growth of human lung carcinoma cell line A549 was examined. We studied on the
      effects of PLME on the release of nitric oxide (NO) in mouse macrophage Raw 264.7
      cells. Treatment of PLME to A549 cells resulted in the growth inhibition,
      morphological change and induction of apoptotic cell death in a dose-dependent
      manner as measured by MTT assay. We found that PLME stimulated a dose-dependent
      increase in NO production. These findings suggest that PLME enhances the anti
      tumoral activity of macrophage and may be a potential therapeutic agent for the
      control of human lung carcinoma cells. 

PMID- 24039489
TI  - New Record of Karoowia saxeti (Stizenb.) Hale in South Korea.
AB  - Karoowia saxeti was recorded during the lichen field expedition in southern part
      of Korea in 2006. The lichen was found on the rock surface along coastal line.
      This species was easily recognized by chemistry (K+ yellow) and the presence of
      isidia. Thallus was saxicolous, subcrustose, more or less lobate at the center
      with clearly lobed margins, 2~6 cm broad and pale yellowish green. Thalli lobes
      were irregular, variable, up to 1.0mm wide, not branched, flat to more or less
      convex and contiguous to subimbricate. Upper surface of the thalli was
      continuous, emaculate, moderately isidiate. The isidia was subglobose to
      cynlindrical, darkening at the tips and unbranched. Low surface of the thalii was
      black with a spongy rhizoidal and lamellar layer. HPLC analysis proved the
      presence of stictic acid (K+ yellow), norstictic acid and usnic acid. This is the
      first record of the species in South Korea. 

PMID- 24039490
TI  - Rhizopus Soft Rot on Pear (Pyrus serotina) Caused by Rhizopus stolonifer in
      Korea.
AB  - Rhizopus soft rot caused by Rhizopus stolonifer occurred on pears (Pyrus
      serotina) in the Jinju City Agricultural Products Wholesale Market in Korea from
      2004 to 2005. The infection usually started from wounds due to cracking at
      harvest time. The lesions started as water-soaked, rapidly softened, then
      gradually expanded. The mycelia grew vigorously on the surface of the fruits and
      formed stolons. Colonies on potato dextrose agar at 25C were white cottony to
      brownish black. Sporangia were globose, black and 90~120 um in size.
      Sporangiophores were light brown and 480~2600 * 12~18 um in size. Sporangiospores
      were globose to oval, brownish, streaked, and 8~14 * 6~10 um in size. Columella
      were light brownish gray, hemispherical and 70~80 um in size. On the basis of
      these symptoms, mycological characteristics and pathogenicity tests on host
      plants, the fungus was identified as Rhizopus stolonifer (Ehrenb.) Vuill. This is
      the first report of rhizopus soft rot on pear (P. serotina) caused by R.
      stolonifer in Korea. 

PMID- 24039491
TI  - Characterization of Sclerotinia sclerotiorum Isolated from Paprika.
AB  - A fungal isolate collected from infected paprika (Capsicum annuum var. grossum)
      was characterized as Sclerotinia sclerotiorum based on its ability of sclerotium
      formation, physiological and molecular properties. When the isolate was grown on
      potato dextrose agar, oatmeal agar, and malt extract agar, it grew most well on
      PDA. Optimal temperature and pH for its growth were 25C and pH 7, respectively.
      The fungal isolate produced sclerotia on PDA within 10 days, and the color and
      shape of the sclerotia were similar to those of S. sclerotiorum . The ITS rDNA
      regions including ITS1 and ITS2 and 5.8S sequences were amplified using ITS1F and
      ITS4 primers from the genomic DNAs of the paprika isolate and other known
      pathogenic S. sclerotiorum isolated from different crops in Korea, and their
      nucleotide sequences were determined. Sequence comparison analysis showed the ITS
      rDNA of the paprika isolate shares 100% sequence identity with those of S.
      sclerotiorum isolated from red pepper, lettuce and a S. sclerotiorum isolate
      registered in GenBank DNA database. Neighbor joining analysis based on the ITS
      rDNA sequence revealed the paprika isolate has very close phylogenetic
      relationships with known Sclerotinia sclerotiorum isolates. This is the first
      report that S. sclerotiorum has been found associated with paprika rot in paprika
      growing countries. 

PMID- 24039492
TI  - Bioconversion of lignocellulose materials.
AB  - One of the most economically viable processes for the bioconversion of many
      lignocellulosic waste is represented by white rot fungi. Phanerochaete
      chrysosporium is one of the important commercially cultivated fungi which exhibit
      varying abilities to utilize different lignocellulosic as growth substrate.
      Examination of the lignocellulolytic enzyme profiles of the two organisms
      Phanerochaete chrysosporium and Rhizopus stolonifer show this diversity to be
      reflected in qualitative variation in the major enzymatic determinants (ie
      cellulase, xylanase, ligninase and etc) required for substrate bioconversion. For
      example P. chrysosporium which is cultivated on highly lignified substrates such
      as wood (or) sawdust, produces two extracellular enzymes which have associated
      with lignin deploymerization. (Mn peroxidase and lignin peroxidase). Conversely
      Rhizopus stolonifer which prefers high cellulose and low lignin containg
      substrates produce a family of cellulolytic enzymes including at least
      cellobiohydrolases and beta-glucosidases, but very low level of recognized lignin
      degrading enzymes. 

PMID- 24039493
TI  - Taxonomic study on Korean Aphyllophorales (5) - on some unrecorded genera and
      species -.
AB  - A total of 149 species and 209 strains of Korean Aphyllophorales in Seoul
      National University Fungus Collection (SFC) were analyzed by taxonomic and
      phylogenetic methods. Among those examined fungal specimens, 9 genera
      Abundisporus, Antrodiella, Cyphellopsis, Dendrothele, Dichomitus, Laxitextum,
      Piloderma, Skeletocutis and Tubulicrinis, and 23 species, Abundisporus
      fuscopurpureus, Antrodiella semisupina, Auriporia pileata, Cantharellus
      subalbidus, Clavulina cinerea, Cyphellopsis confusa, Dendrothele acerina,
      Dichomitus campestris, Haplotrichum aureum, Heterobasidion annosum, Hyphoderma
      argillaceum, Hyphodontia tropica, Inonotus dryophilus, Ischnoderma benzoinum,
      Laxitextum bicolor, Phanerochaete radicata, Phellinus lonicericola, Piloderma
      byssinum, Skeletocutis nivea, Tomentella terrestris, Trametes elegans, Trametes
      tenuis, and Tubulicrinis accedens were confirmed as new to Korea and registered
      here with descriptions. 

PMID- 24039494
TI  - Two new records of penicillium associated with blue moldy bulbs of lily in Korea.
AB  - Two new records of Penicillium from blue moldy bulbs of lily are reported in
      Korea. The Korean isolates of P. albocoremium (Frisvad) Frisvad and P. tulipae
      Overy and Frisvad were phylogenetically identical to the reference species based
      on DNA sequence of the beta-tubulin gene. P. albocoremium and P. tulipae are
      described and illustrated. 

PMID- 24039495
TI  - Diversity of keratinophilic fungi on human hairs and nails at four governorates
      in upper egypt.
AB  - The mycobiota of 160 hair and nail samples collected from 4 different
      governorates in upper Egypt were estimated using soil plate method for isolating
      keratinophilic and dermatophytic fungi. Twenty-three fungi were recorded on both
      hair and nail samples collected from the four governorates. Highest fungal
      diversity (20) was collected from Red Sea samples followed by Qena (18) and Aswan
      (17) while lowest fungal diversity was recorded from Sohage samples. The common
      genera were Aphanoascus, Aspergillus, Penicillium, Paecilomyces and
      Chrysosporium. The most prevalent species belonging to these genera were: A.
      fulvescens, Aphanoascus sp. A. flavus link, A. flavus var. columnaris, P.
      chrysogenium. P. lilacinus and C. sulfureum. True dermatophytes such as Nannizzia
      fulva appeared in 20~30% of the male samples. 

PMID- 24039496
TI  - Diversity of Endophytic Fungi Associated with Taraxacum coreanum and Their
      Antifungal Activity.
AB  - Endophytic fungi were isolated from healthy leaf and root samples of Taraxacum
      coreanum. Of the 72 isolates recovered, 39 were from leaves and 33 from roots
      with an isolation frequency of 54% and 46%, respectively. Based on ITS sequence
      analysis, 72 isolates were classified into 19 genera of which 17 were under the
      phylum Ascomycota and 2 were under Basidiomycota. Diverse genera were found and
      Alternaria, Cladosporium, Fusarium and Phoma were dominant. Out of 19 genera,
      Apodus, Ceriporia, Dothideales, Leptodontidium, Nemania, Neoplaconema,
      Phaeosphaeria, Plectosphaerella and Terfezia were new to Korea. Seventy two
      isolates were screened for antifungal activity, of which 10 isolates (14%) were
      found active at least against one of the tested fungi. Isolate 050603 had the
      widest antifungal spectra of activity, and isolates 050592 and 050611 were active
      against three plant pathogenic fungi. 

PMID- 24039497
TI  - Effects of Ectomycorrhizal Fungi on Growth of Seedlings of Pinus densiflora.
AB  - This study was conducted to investigate the different effects of ectomycorrhizal
      fungal (ECMF) species on the growth of seedlings of Pinus densiflora, and the
      effects of ECMF diversity on plant productivity. A total of five species of ECMF
      were isolated from root tips of pine seedlings collected from Mt. Songni and used
      as inocula. Pots containing pine seedlings were inoculated with either a single
      ECMF species or a mixture of five ECMF species. All of the seedlings formed ECM
      on their roots except for the control plants. The pine seedlings' growth
      responses varied by the different ECMF species. Also, pine seedlings inoculated
      with a mixture of five ECMF species showed the highest growth response. The
      results of the study suggest that the colonization of diverse species of ECMF
      will increase plant productivity, and the selection of suitable ECMF species
      could be an important factor for plant growth. 

PMID- 24039498
TI  - Effect of Preservation Periods and Subcultures on Fruiting Body Formation of
      Cordyceps militaris In Vitro.
AB  - Effects of various preservation periods and subcultures on fruiting body
      formation of Cordyceps militaris were investigated using EFCC C-10995 single
      ascospore strains. Fruiting body formation by original strains was profuse when
      preserved at 4C for 5~6 months. Fruiting from subcultures was stable till second
      to sixth subcultures, after which it decreased sharply. The more the colony color
      of subcultures changed, the less the fruiting bodies formed. Liquid inoculum
      preparation of single ascospore strains in the same or separate broths did not
      affect fruiting body formation. Similarly, two strains C-10995-3 and C-10995-6 in
      different numbers during liquid inoculum preparation produced similar fruiting
      bodies. 

PMID- 24039499
TI  - The Culture Conditions for the Mycelial Growth of Phellinus spp.
AB  - Phellinus genus belonged to Hymenochaetaceae of Basidiomycetes and has been well
      known as one of the most popular medicinal mushrooms due to high antitumor
      activity. This study was carried out to obtain the basic information for mycelial
      culture conditions of Phellinus linteus, P. baumii, and P. gilvus. According to
      colony diameter and mycelial density, the media for suitable mycelial growth of
      them were shown in MEA, glucose peptone, and MCM. The optimum temperature for
      mycelial growth was 30C. Carbon and nitrogen sources were mannose and malt
      extract, respectively. The optimum C/N ratio was 10 : 1 to 5: 1 with 2% glucose
      concentration, vitamin was thiamine-HCl, organic acid was succinic acid, and
      mineral salt was MgSO4.7H2O. 

PMID- 24039500
TI  - The Fruiting Body Formation of Armillaria mellea on Oak Sawdust Medium Covered
      with Ground Raw Carrots.
AB  - To produce an artificial fruiting body of Armillaria mellea on the oak sawdust
      medium, seven strains of A. mellea were used. The top surface of oak sawdust
      medium covered with ground raw carrot was inoculated with each of 7 strains and
      cultured for 30 days at 25C in the dark condition until the mycelia of A. mellea
      completely colonized the medium from top to bottom. Then, the mycelia which were
      fully covered on the top surface of the medium were scratched slightly with a
      spatula and filled with tap water for 3 hours. To induce the primordial
      formation, the 7 strains of A. mellea were transferred to the growth chamber
      under the illumination (350 lux) of 12 hours and relative humidity of 85 +/- 5%
      in a day and then cultured at 16 +/- 1C. Only A. mellea IUM 949 could form
      primordia on the sawdust medium, but the other strains did not make primordia at
      the same condition. The primordia of A. mellea IUM 949 were formed 10 days after
      complete colonization of the medium and the fruiting bodies were produced 7 days
      after a primordial formation. The experimental results suggested that IUM 949
      strain might be a good candidate for mass production of fruiting bodies of A.
      mellea. 

PMID- 24039501
TI  - Genes Expressed During Fruiting Body Formation of Agrocybe cylindracea.
AB  - Agrocybe cylindracea, an edible mushroom belonging to Bolbitiaceae, Agaricales,
      is widely used as invaluable medicinal material in the oriental countries. This
      study was initiated to find the genes expressed during the fruiting body
      formation of A. cylindracea. The cDNAs expressed differentially during fruiting
      body morphogenesis of A. cylindracea were isolated through subtractive
      hybridization between vegetative mycelia and fruiting bodies. The cDNAs expressed
      in the fruiting body morphogenesis of A. cylindracea were cloned and twenty genes
      were identified. Eleven were homologous to genes of known functions, three were
      homologous to genes in other organism without any function known. Six were
      completely novel genes specific to A. cylindracea so far examined. Some genes
      with known functions were a pleurotolysin, a self-assembling poreforming
      cytolysins; Aa-Pri1 and Pir2p, specifically induced genes during fruiting
      initiation of other mushroom, Agrocybe aegerita; an amino acid permease; a
      cytochrome P450; a MADS-box gene; a peptidylprolyl isomerase; and a serine
      proteinase. For other clones, no clear function was annotated so far. We believe
      the first report of the differentially expressed genes in fruiting process of A.
      cylindracea will be great helps for further research. 

PMID- 24039502
TI  - Antifungal Activities of Biorelevant Complexes of Copper(II) with Biosensitive
      Macrocyclic Ligands.
AB  - Four copper(II) complexes have been prepared using macrocyclic ligands. The
      macrocyclic ligands have been synthesized by the condensation reaction of diethyl
      phthalate with Schiff bases derived from o-phenylene diamine and Knoevenagel
      condensed beta-ketoanilides (obtained by the condensation of acetoacetanilide and
      substituted benzaldehydes). The ligands and copper complexes have been
      characterized on the basis of Microanalytical, Mass, UV-Vis., IR and CV spectral
      studies, as well as conductivity data. On the basis of spectral studies, a square
      planar geometry for the copper complexes has been proposed. The in vitro
      antifungal activities of the compounds were tested against fungi such as
      Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola
      and Candida albicans. All the synthesized copper complexes showed stronger
      antifungal activities than free ligands. The minimum inhibitory concentrations
      (MIC) of the copper complexes were found in the range of 8~28 ug/ml. These
      compounds represent a novel class of metal-based antifungal agents which provide
      opportunities for a large number of synthetic variations for modulation of the
      activities. 

PMID- 24039503
TI  - Antimicrobial activity of some essential oils against microorganisms
      deteriorating fruit juices.
AB  - Seventeen microbial species including 10 fungal taxa, two yeasts and five
      bacteria, were isolated from freshly prepared orange, guava and banana juices
      kept in open bottles at room temperature for 7 days. Eight different essential
      oils, from local herbs, were tested for their antimicrobial activity against
      these test organisms. The essential oils of Cymbopogon citratus, Ocimum basilicum
      and Origanum majorana were found to be highly effective against these
      microorganisms. Aspergillus niger, A. flavus and Saccharomyces cerevisiae, the
      most prevalent microorganisms in juice, showed the highest resistance against
      these essential oils. GC-MS analysis showed that while e-citral, a'-myrcene, and
      z-citral represent the major components (75.1%) of the essential oil of
      Cymbopogon citratus; bezynen,1-methyl-4-(2-propenyl), 1,8-cineole and trans-a'
      bisabolene were the main components (90.6%) of Ocimum basilicum; whereas 3
      cyclohexen-1-01,4-methyl-1(1-methylethyl)-(CAS), c-terpinene and trans
      caryophyllene represent the major components (65.1%) of Origanum majorana. These
      three essential oils were introduced into juices by two techniques namely,
      fumigation and direct contact. The former technique showed more fungicidal effect
      than the latter one against A. flavus, A. niger, and S. cerevisiae. The essential
      oil of Cymbopogon citratus by comparison to other test oils showed the strongest
      effect against these fungi with a minimum inhibitory concentration of 1.5 ul/ml
      medium and a sublethal concentration of 1.0 ul/ml. The antimicrobial activity of
      this oil is thermostable at 121C for 30 min. 

PMID- 24039504
TI  - Antitumor and Antioxidant Activities of the Extracts from Fruiting Body of
      Phellinus linteus.
AB  - Fruiting bodies of Phellinus linteus were extracted by hot water and alkali
      methods. Sugar contents of PL-H (hot water extract) and PL-A (alkali water
      extract) were 81.1%, 37.4% and protein contents were 6.2%, 21.8%, respectively.
      Amino acid pattern showed that two extracts contained large amount of aspartic
      acid and alanine. Two extracts showed characteristic IR absorption pattern for
      glycosidic bond at 890 cm(-1). PL-H was divided two fractions by gel filtration
      chromatography and the molecular weights of each fraction were estimated to be
      about 10 kD and 225 kD, respectively and also PL-A was estimated 10 kD. Two
      extracts showed strong antitumor, immunomodulating and antioxidant activities,
      and were compared with commercialized glycopeptide anticancer drugs. 

PMID- 24039505
TI  - Effect of a Pholiota adiposa Extract on Fat Mass in Hyperlipidemic Mice.
AB  - The purpose of this study was to investigate the effect of a Pholiota adiposa
      extract on fat mass in hyperlipidemic mice fed on a high-fat diet. The water
      extracts from P. adiposa (ASI 24018) were not affected in the total triglyceride
      contents and epididymal fat mass in mice fed on a high-fat diet, but the
      retroperitoneal fat mass decreased significantly. This result suggests that the
      P. adiposa extract may be a potential candidate for use as a functional food that
      can act as a prophylactic against hyperlipidemia. However, the P. adiposa extract
      showed no effect in the total triglyceride contents and epididymal fat mass. 

PMID- 24039506
TI  - How Should We Treat Depression in Patients with Cardiovascular Disease?
AB  - Among patients with cardiovascular disease (CVD), depression is highly prevalent
      and is associated with worse cardiovascular prognosis and lower quality of life.
      Treatments for depression in CVD patients produce modest, but clinically
      significant reductions in depressive symptoms and show promise for improving
      cardiovascular prognosis. While tricyclics should generally be avoided,
      antidepressants from multiple other classes appear to be safe in cardiac
      patients. A strategy of engaging patients in choosing medications or
      psychotherapy and then intensifying treatment to therapeutic goal appears to be
      more effective at reducing depression than single mode interventions.
      Recommendations for screening all CVD patients for depression may be premature
      given increased costs associated with screening and gaps in knowledge about the
      risk-benefit ratio of depression treatment in mild and moderately depressed
      patients.

PMID- 24039507
TI  - Sixth European hemiptera congress.

PMID- 24039508
TI  - Morphological differences among egg nests and adult individuals of Cicadatra
      persica (Hemiptera, Cicadidae), distributed in Erneh, Syria.
AB  - The aim of this study is determining the different patterns of egg nests and the
      morphological differences between the specimens of Cicadatra persica Kirkalidy,
      1909 (Hemiptera: Cicadidae) distributed in fruit orchards in Erneh located on AL
      Sheikh mountain south west of Syria. The appearance of 80 egg nests was studied,
      and the results showed that there were two basic patterns of egg nests laid by
      Cicadatra persica, 90% of the egg nests were of the first pattern (consists of
      several adjacent slits), while 10% of them were of the second pattern (consists
      of several divergent slits). A random sample consisting of 300 specimens (150
      males and 150 females) were also studied concentrating on the differences in the
      color of the supra-antennal plate and in the number of spurs on the tibia of the
      hind legs. The results showed that there were two basic patterns of individuals
      based on the differences in the color of supra-antennal plate. The first pattern
      (individuals with yellow supra-antennal plates), constituted more than 90%, and
      the second one (individuals with black supra-antennal plates) constituted less
      than 10%. The results also showed that there were 27 different patterns based on
      the number of spurs on the tibia of the hind legs. One of them was a common
      pattern (2, 3) whose individuals have 2 spurs on the upper side of the tibia of
      the hind legs and 3 spurs on the lateral side of the tibia of the hind legs. The
      total percent of this common pattern was 76%. The other 26 patterns were
      different from each other, and the total percent of all these different patterns
      was 24%. 

PMID- 24039509
TI  - Thorax morphology of selected species of the genus Cacopsylla (Hemiptera,
      Psylloidea).
AB  - The paper concerns with characteristics of a thorax morphological structure
      Cacopsylla Ossiannilsson, 1970 species, referring to an analysis of five species
      classified in the past in three subgenera. The structure of the sternites,
      tergites and pleurites of all the parts of the thorax was studied by a scanning
      microscope. Descriptions of particular elements building up thorax plates, their
      shape, size and links as well as a course of all the clefts and sulcus are
      provided. The study of thorax morphology of Cacopsylla species suggests that the
      thorax morphology is relatively homogenous within a genus. 

PMID- 24039510
TI  - The genus Cahara Ghauri, 1978 of China (Hemiptera, Heteroptera, Pentatomidae,
      Halyini) with descriptions of two new species.
AB  - Cahara Ghauri from China with three species is reviewed here. Two of them, Cahara
      incisura sp. n. and Cahara nodula sp. n. are described here. Key to the three
      Chinese species, habitus photographs and illustrations of genitalia are also
      provided. All examined materials including the types of three species mentioned
      are deposited in the Institute of Entomology, Nankai University, Tianjin, China
      (NKUM). 

PMID- 24039511
TI  - First record of Graphosoma inexpectatum (Hemiptera, Pentatomidae, Podopinae) from
      Turkey with description of the female.
AB  - Graphosoma inexpectatum Carapezza & Jindra, 2008 is described from Syria, the
      southern neighbor of Turkey, and is known only from the type locality. The first
      observation of the species in Turkey dates back to 1995 with two females obtained
      from the provinces of Gaziantep (Sehitkamil-Aktoprak) and Adana (Pozanti-Burucek
      Plateau). These two localities are situated inside the part of the Mediterranean
      region along the Syrian border. Females of the species, whose original
      description was based on males, are described here for the first time. A map
      showing the collecting localities and photographs of the female specimens are
      given. 

PMID- 24039512
TI  - Comparative morphology of immature stages of four species of Chinavia (Hemiptera,
      Pentatomidae), with a key to the species of Rio Grande do Sul, Brazil.
AB  - Chinavia Orian (1965) is one of the most diverse genera of Pentatomidae,
      distributed in the Afrotropical, Neotropical and Nearctic Regions. Thirty-two
      species are recorded for Brazil, some of them having potential economic impact
      because they are found on crops and referred to as pests. The morphology of the
      five nymphal instars of Chinavia armigera (Stal, 1859), Chinavia aseada (Rolston,
      1983), Chinavia brasicola (Rolston, 1983) and Chinavia runaspis (Dallas, 1851)
      are described here. Through a comparative study, identification keys were
      developed to allow an early identification of the 12 Chinavia species of Rio
      Grande do Sul. 

PMID- 24039513
TI  - New distributional and bioacoustic data about Cicadivetta goumenissa from
      Peloponnese, Greece (Hemiptera, Cicadidae).
AB  - Cicadivetta goumenissa, a small singing cicada described recently by Gogala et
      al. (2012), has been previously found only around the village of Goumenissa in
      northern Peloponnese. We visited this area again in June 2012 and tried to
      determine the distribution range of this species. We found Cicadivetta goumenissa
      in some further localities, but all within a very small area of about 15 by 25
      km. We also made more than one hour of new song recordings and extended our
      knowledge of the song repertoire of this species. 

PMID- 24039514
TI  - Aquatic Heteroptera (Nepomorpha, Gerromorpha) in small intermittent rivers of
      Ukraine steppe zone.
AB  - Small intermittent rivers are some of the most widespread types of water currents
      in the steppe zone. In the ecosystems of the intermittent rivers we have found 28
      species of water bugs that compose the majority of the described fauna in the
      south Ukraine. Our study added two new species to the faunistic list of this zone
      (Sigara fossarum, Hydrometra gracilenta), and finally confirmed the presence of
      Micronecta scholtzi in Ukraine. We also studied the seasonal changes of biotopic
      distribution and quantitative characteristics of aquatic Heteroptera. It was
      shown thatfor water bugs the ecosystem of the small intermittent rivers consists
      of three closely connected components: the riverbed, the flooded areas and the
      extra inundated constant basins. During the droughty period when the riverbed is
      dry, the extra inundated basins (including artificial ones - sandy pits) serve as
      refugia. The wintering of many species takes place there, especially when the
      riverbed is not filled before the cold period. However, the reproduction of most
      species takes place in the riverbed and associated flooded areas. Thus, this work
      is a confirmation and development of the concept for "a uniform architectonic
      complex of a river valley". 

PMID- 24039515
TI  - Sex chromosome pre-reduction in male meiosis of Lethocerus patruelis (Stal, 1854)
      (Heteroptera, Belostomatidae) with some notes on the distribution of the species.
AB  - The karyotype and meiosis in males of giant water bug Lethocerus patruelis
      (Heteroptera: Belostomatidae: Lethocerinae) were studied using standard and
      fluorochrome (CMA3 and DAPI) staining of chromosomes. The species was shown to
      have 2n = 22A + 2m + XY where 2m are a pair of microchromosomes. NORs are located
      in X and Y chromosomes. Within Belostomatidae, Lethocerus patruelis is unique in
      showing sex chromosome pre-reduction in male meiosis, with the sex chromosomes
      undergoing reductional division at anaphase I and equational division at anaphase
      II. Cytogenetic data on the family Belostomatidae are summarized and compared. In
      addition, the structure of the male internal reproductive organs of Lethocerus
      patruelis is presented, the contemporary distribution of Lethocerus patruelis in
      Bulgaria and in the northern Aegean Islands is discussed, and the first
      information about the breeding and nymphal development of this species in
      Bulgaria is provided. 

PMID- 24039516
TI  - New aradidae from ecuador (hemiptera, heteroptera, aradidae).
AB  - As an addition to the presently poorly known aradid fauna of Ecuador, 3 new
      genera and 4 new species are described: Osellaptera setifera gen. n., sp. n.;
      Kormilevia ecuadoriana sp. n. both belonging to Mezirinae; and
      CarventinaeCotopaxicoris cruciatus gen. n., sp. n. and Onorecoris piceus gen. n.,
      sp. n. An updated key is provided for all species of the Neotropical genus
      Kormilevia Usinger & Matsuda, 1959. 

PMID- 24039517
TI  - The Auchenorrhyncha fauna of peat bogs in the Austrian part of the Bohemian
      Forest (Insecta, Hemiptera).
AB  - The first overview on the Auchenorrhyncha fauna of peat bogs of the Austrian
      Bohemian Forest is presented. Seven oligotrophic peat bog sites were studied in
      2011 by suction sampler ("G-Vac") and 93 Auchenorrhyncha species (with 7465 adult
      specimens) were recorded. Eleven species (about 18 % of the individuals) are
      tyrphobiontic or tyrphophilous. The relative species abundance plot is not very
      steep; the six most abundant species represent 50 % of the individuals. The most
      common species is Conomelus anceps (17 % of the individuals). Compared to the
      whole Austrian Auchenorrhyncha fauna, the fauna of peat bogs comprises distinctly
      more univoltine species and more species hibernating in nymphal stage. Densities
      of adult Auchenorrhyncha in peat bogs are low in spring (about 10-60 individuals
      per m2) and high in July, with up to 180 (+/-50) individuals per m2. Disturbed
      peat bogs have higher species numbers and higher Auchenorrhyncha densities in
      total, but lower numbers and densities in peat bog specialists. 

PMID- 24039518
TI  - Redescription of Urartucoris ermolenkoi (Hemiptera, Heteroptera, Coreidae) and a
      revised key to the genera of Pseudophloeini of the Western Palaearctic Region.
AB  - Urartucoris ermolenkoi P. V. Putshkov, 1979 (Hemiptera: Heteroptera: Coreidae:
      Pseudophloeinae) is recorded from Turkey for the first time. Redescriptions of
      the genus and species are provided, the male of Urartucoris ermolenkoi being
      described for the first time, and intraspecific variability of the species is
      discussed. Adults of Urartucoris ermolenkoi were collected from mid April to end
      of July and in mid September by means of pitfall traps. First data on the habitat
      of the species are provided: it is epigeic, inhabiting sparse forests and
      shrublands at higher elevations (ca. 1400-1600 m a.s.l.) in arid regions of
      central Anatolia. A revised key to the genera of the West Palaearctic
      Pseudophloeini is provided. Translations of the original descriptions from
      Russian are given in Appendix. 

PMID- 24039519
TI  - Taxonomic changes in some predominantly Palaearctic distributed genera of Drymini
      (Heteroptera, Rhyparochromidae).
AB  - The history of the taxonomic research of Rhyparochromidae and especially Drymini
      is briefly reviewed. Two new species level synonyms are proposed: Taphropeltus
      javanus Bergroth, 1916, syn. n. = Taphropeltus australis Bergroth, 1916, syn. n.
      = Brentiscerus putoni (Buchanan White, 1878). A monotypic new genus, Malipatilius
      gen. n. (type species: Scolopostethus forticornis Gross, 1965 from Australia) is
      established. 

PMID- 24039520
TI  - New data on aphid fauna (Hemiptera, Aphididae) in Algeria.
AB  - A survey of aphids was carried out during the period 2008-2011 in different
      regions of Algeria by collecting and identifying aphids and their host plants.
      Aphids were collected from 46 host plants. Forty-six species were reported
      including thirty-six species which were recorded for the first time in this
      country and thirty species which were recorded for the first time in the Maghreb
      (North Africa). This study extends the number of known Algerian aphid to 156
      species. 

PMID- 24039521
TI  - A preliminary study on the distribution patterns of endemic species of
      Fulgoromorpha (Hemiptera, Auchenorrhyncha) in Iran.
AB  - Iran is known as the most complex and varied country in southwest Asia, in terms
      of geography, vegetation, climate and consequently biological diversity. The
      rather high number of recorded endemic species of Fulgoromorpha in Iran indicates
      a high potential for speciation in some areas. In this study, in order to
      identify the endemic zones for Fulgoromorpha of Iran, three main biogeographic
      regions of the country were divided into 13 primary zones, mainly according to
      the distribution of published and unpublished locality records of endemic
      species. Using Venn diagrams and cluster analyses on the primary zones, 6 final
      endemic zones were recognized: Caspian zone, southern slopes of Alborz, Zagros
      Mountains, Kerman Mountains, Khorasan Mountains, and Baluchestan and Persian Gulf
      coasts. Then a similarity map was produced for endemic zones using a
      Multidimensional analysis (Alscal) and the differences between the positions of
      the same zones in the similarity and geographic maps were discussed. 

PMID- 24039522
TI  - Trigonocranus emmeae Fieber, 1876 (Hemiptera, Fulgoromorpha, Cixiidae) - a new
      species for Poland.
AB  - Single macropterous female of Trigonocranus emmeae Fieber, 1876 has been found
      during the faunistic studies in semi-natural plant communities of Oswiecim city
      in southern Poland. It is the first record of this species in Poland.
      Trigonocranus emmeae is rarely collected within the wide range of its
      distribution, mostly due to its hidden life mode. 

PMID- 24039523
TI  - Mitochondrial COI and morphological specificity of the mealy aphids (Hyalopterus
      ssp.) collected from different hosts in Europe (Hemiptera, Aphididae).
AB  - Forty three European population samples of mealy aphids from various winter and
      summer host plants were attributed to respective species of Hyalopterus by means
      of their partial sequences of mitochondrial COI gene. Used Hyalopterus samples
      emerged as monophyletic relative to outgroup and formed three major clades
      representing three host specific mealy aphid species in the Neighbor joining,
      Maximum parsimony, Maximum likelihood and Bayesian inference trees. Hyalopterus
      pruni and Hyalopterus persikonus emerged as a sister species, whilst Hyalopterus
      amygdali was located basally. Samples representing different clades in the
      molecular trees were used for canonical discrimination analysis based on twenty
      two morphological characters. Length of the median dorsal head hair enabled a
      97.3 % separation of Hyalopterus amygdali from the remaining two species. No
      single character enabled satisfactory discrimination between apterous viviparous
      females of Hyalopterus pruni and Hyalopterus persikonus. A modified key for the
      morphological identification of Hyalopterus species is suggested and their
      taxonomic status discussed. 

PMID- 24039524
TI  - Preliminary study of wing interference patterns (WIPs) in some species of soft
      scale (Hemiptera, Sternorrhyncha, Coccoidea, Coccidae).
AB  - The fore wings of scale insect males possess reduced venation compared with other
      insects and the homologies of remaining veins are controversial. The hind wings
      are reduced to hamulohalterae. When adult males are prepared using the standard
      methods adopted to females and nymphs, i.e. using KOH to clear the specimens, the
      wings become damaged or deformed, an so these structures are not usually
      described or illustrated in publications. The present study used dry males
      belonging to seven species of the family Coccidae to check the presence of
      stable, structural colour patterns of the wings. The visibility of the wing
      interference patterns (WIP), discovered in Hymenoptera and Diptera species, is
      affected by the way the insects display their wings against various backgrounds
      with different light properties. This frequently occurring taxonomically specific
      pattern is caused by uneven membrane thickness and hair placement, and also is
      stabilized and reinforced by microstructures of the wing, such as membrane
      corrugations and the shape of cells. The semitransparent scale insect's fore
      wings possess WIPs and they are taxonomically specific. It is very possible that
      WIPs will be an additional and helpful trait for the identification of species,
      which in case of males specimens is quite difficult, because recent coccidology
      is based almost entirely on the morphology of adult females. 

PMID- 24039526
TI  - Madagascar Flatidae (Hemiptera, Fulgoromorpha): state-of-the-art and research
      challenges.
AB  - The paper provides a historical review of the research on Flatidae in Madagascar
      and indicates future prospects. While the first two species of Madagascar
      Flatidae were described by Guerin-Meneville (1844), it was Signoret (1860) who
      made the first real attempt to enhance our knowledge of the Hemiptera fauna of
      Madagascar by describing several additional species. Over the following century
      and a half, several investigators have turned their attention to this group of
      insects, with the final number of species recorded for the island reaching 79.
      Despite this long history of research, it is evident that much still remains to
      be done. Detailed taxonomic research will allow the natural history of Madagascar
      and changes in the biological diversity of its endemic ecosystems to be better
      understood. This paper should be considered as an introduction to a complex study
      on the systematics and phylogeny of worldwide Flatidae planthoppers. 

PMID- 24039525
TI  - First report on C-banding, fluorochrome staining and NOR location in holocentric
      chromosomes of Elasmolomus (Aphanus) sordidus Fabricius, 1787 (Heteroptera,
      Rhyparochromidae).
AB  - In spite of various cytogenetic works on suborder Heteroptera, the chromosome
      organization, function and its evolution in this group is far from being fully
      understood. Cytologically, the family Rhyparochromidae constitutes a
      heterogeneous group differing in chromosome numbers. This family possesses XY sex
      mechanism in the majority of the species with few exceptions. In the present
      work, multiple banding techniques viz., C-banding, base-specific fluorochromes
      (DAPI/CMA3) and silver nitrate staining have been used to cytologically
      characterize the chromosomes of the seed plant pest Elasmolomus (Aphanus)
      sordidus Fabricius, 1787 having 2n=12=8A+2m+XY. One pair of the autosomes was
      large while three others were of almost equal size. At diplotene, C-banding
      technique revealed, that three autosomal bivalents show terminal constitutive
      heterochromatic bands while one medium sized bivalent was euchromatic.
      Microchromosomes (m-chromosomes) were positively heteropycnotic. After DAPI and
      CMA3 staining, all the autosomal bivalents showed equal fluorescence, except CMA3
      positive signals, observed at both telomeric heterochromatic regions of one
      medium sized autosomal bivalent. Silver nitrate staining further revealed that
      this chromosome pair carries Nucleolar Organizer Regions (NORs) at the location
      of CMA3 positive signals. The X chromosome showed a thick C-band, positive to
      both DAPI /CMA3 while Y, otherwise C-negative, was weakly positive to DAPI and
      negative to CMA3, m-chromosomes were DAPI bright and CMA3 dull. 

PMID- 24039527
TI  - The unusual Afrotropical and Oriental leafhopper subfamily Signoretiinae
      (Hemiptera, Cicadellidae): taxonomic notes, new distributional records, and
      description of two new Signoretia species.
AB  - The leafhopper subfamily Signoretiinae is redescribed and includes two tribes:
      Signoretiini Baker and Phlogisini Linnavuori. Redescriptions of included tribes,
      diagnoses and a taxonomic key to genera are provided. New records for genera of
      Signoretiinae are as follows: Phlogis in Central African Republic, Malaysia and
      Thailand; Preta in Thailand; and Signoretia in the Republic of the Congo, Zambia,
      Thailand, Vietnam, and Taiwan (China). Signoretia pacifica is newly recorded from
      Cameroon. In addition, detailed illustrations of the male genitalia of the
      previously described species, Chouious tianzeus, Preta gratiosa,and Signoretia
      yangli are provided; the male genitalia of Signoretia malaya are described for
      the first time; and two new species of Signoretia are described, Signoretia
      delicata sp. n. from the Philippinesand Signoretia kintendela sp. n. from the
      Republic of the Congo. 

PMID- 24039528
TI  - Two new species of Vertomannus Distant, 1903 (Heteroptera, Rhyparochromidae,
      Ozophorini), with proposal of a new subgenus.
AB  - Two new Vertomannus species, Vertomannus flavus sp. n. (south Vietnam) and
      Vertomannus borneensis sp. n. (Borneo) are described. Vertomannus
      (Elongatomannus), subgen. n. (type species: Vertomannus flavus) is proposed. 

PMID- 24039529
TI  - Monitoring of aphid flight activities in seed potato crops in Serbia.
AB  - Aphid flight activities in seed potato fields have been studied by the yellow
      water traps. It is a good method for monitoring aphids as vectors of viruses, but
      this study also showed it is a suitable method for insect-diversity research.
      During the four-year studies, over 11.500 specimens were collected and a total of
      107 different taxa of aphids were identified. The most abundant species were
      polyphagous species, such as: Acyrthosiphon pisum (Haris), Aphis fabae Scopoli,
      Aphis gossypii Gloverand Brachycaudus helichrysi (Kaltenbach). The results of the
      studies show that diversity of aphids in different regions of Serbia is similar
      regardless of the altitude and the diversity of terrain. At most sites it ranged
      from 2 to 3. The highest value was recorded in Begec, locality in northern part
      of Serbia, in year 2008, and it was 2.92. The maximum values of the Shannon
      Weaver diversity index at all sites were recorded in the first weeks of the
      monitoring of aphid flight activities. Morisita-Horn similarity index shows no
      significant differences between sites regardless of altitudes. The sites are
      grouped by year, not by similarity of relief. In spite of these results, the Chi
      square analysis showed highly significant difference in vector frequencies among
      seasons and sites with more pronounced differences for PVY. As a consequence of
      differences in vector frequencies, the vector pressure index in some regions was
      different also. The number of vectors and vector pressure index vary depending on
      the altitude of localities. At localities at altitudes under 1000 m, they were
      high. The highest index was at Kotraza, locality in central part of Serbia, in
      2007, when PVY index exceeded the value of 180, while for PLRV it was 60. At high
      altitudes on mountain Golija, above 1100 m, the number of aphids was low, as well
      as the vector pressure index which indicates that these regions are suitable for
      producing virus-free seed potato. 

PMID- 24039530
TI  - Aphids (Hemiptera, Aphididae) on ornamental plants in greenhouses in Bulgaria.
AB  - Investigations on the species composition and host range of aphids on ornamental
      greenhouse plants in Bulgaria was conducted over a period of five years, from
      2008 to 2012. Twenty greenhouses, growing ornamentals for landscaping, plant
      collections and other purposes were observed. They were located in the regions of
      Sofia, Plovdiv, Smolyan, Pavlikeni, Varna and Burgas. The total number of
      collected aphid samples was 279. Their composition included 33 aphid species and
      one subspecies from 13 genera and 5 subfamilies. Twenty-eight species were found
      to belong to subfamily Aphidinae. Almost 70 % of all recorded species were
      polyphagous. The most widespread aphid species was Myzus persicae, detected in 13
      greenhouses all year round, followed by Aulacorthum solani (10 greenhouses) and
      Aphis gossypii (9 greenhouses). The widest host range was shown by Myzus persicae
      (43 hosts), Aulacorthum solani (32 hosts) and Aulacorthum circumflexum (23
      hosts). The list of host plants includes 114 species from 95 genera and 58
      families. The greatest variety of aphid species was detected on Hibiscus (9
      species). Out of all aphid samples 12.9 % were collected on Hibiscus and 6.8 %,
      on Dendranthema. The greatest variety of aphid species was detected on Hibiscus
      (9 species). Periphyllus californiensis and Aphis (Aphis) fabae mordvilkoi are
      reported for the first time for Bulgaria. Furthermore, Aphis spiraecola has been
      found in new localities and has widened its host range in this country. 

PMID- 24039531
TI  - Secondary structure models of 18S and 28S rRNAs of the true bugs based on
      complete rDNA sequences of Eurydema maracandica Oshanin, 1871 (Heteroptera,
      Pentatomidae).
AB  - The sequences of 18S and 28S rDNAs have been used as molecular markers to resolve
      phylogenetic relationships of Heteroptera for two decades. The complete sequences
      of 18S rDNAs have been used in many studies, while in most studies only partial
      sequences of 28S rDNAs have been used due to technical difficulties of amplifying
      the complete lengths. In this study, we amplified the complete 18S and 28S rDNA
      sequences of Eurydema maracandica Oshanin, 1871, and reconstructed the secondary
      structure models of the corresponding rRNAs. In addition, and more importantly,
      all of the length variable regions of 18S rRNA were compared among 37 families of
      Heteroptera based on 140 sequences, and the D3 region of 28S rRNA was compared
      among 51 families based on 84 sequences. It was found that 8 length variable
      regions could potentially serve as molecular synapomorphies for some monophyletic
      groups. Therefore discoveries of more molecular synapomorphies for specific
      clades can be anticipated from amplification of complete 18S and 28S rDNAs of
      more representatives of Heteroptera. 

PMID- 24039532
TI  - Stoneflies of the genus Neoperla (Plecoptera, Perlidae) from Wuyi Mountain
      National Nature Reserve, Fujian of China.
AB  - The species of the genus Neoperla are reviewed from Wuyi Mountain National Nature
      Reserve located in the Fujian Province of southeastern China, including the
      description of a new species, Neoperla brevistyla sp. n. The new species is
      compared to similar taxa. The first records of five Neoperla species, Neoperla
      henana Li, Wu & Zhang, 2011, Neoperla similiserecta Wang & Li, 2012, Neoperla
      qingyuanensis Yang & Yang, 1995, Neoperla xuansongae Li & Li, 2013 and Neoperla
      tuberculata Wu, 1938 are given for the Wuyi Mountain. A provisional key is
      provided for facilitating the identification of these species. 

PMID- 24039533
TI  - Pengzhongiella daicongchaoi gen. et sp. n., a remarkable myrmecophile
      (Staphylinidae, Pselaphinae, Batrisitae) from the Gaoligong Mountains.
AB  - A new genus and species, Pengzhongiella daicongchaoi, of the subtribe Batrisina
      (Batrisitae: Batrisini) is described from the Gaoligong Mountains, Yunnan,
      Southwest China. Adults were collected in a colony of Odontomachus monticola, and
      presented reduction of certain external characters and elongate appendages
      relating to myrmecophily. Description and illustrations of the habitus and major
      diagnostic features of the new taxon are provided; a brief discussion of its
      taxonomic placement is included. The new species also represents the first record
      of a Pselaphinae in association with an Odontomachus ant. 

PMID- 24039534
TI  - On Levymanus, a remarkable new spider genus from Israel, with notes on the
      Chediminae (Araneae, Palpimanidae).
AB  - Levymanus gershomi gen. n. et sp. n., is described from southern Israel. The eye
      arrangement and structure of the male palp indicate that this genus belongs to
      Chediminae Simon, 1893. Levymanus gen. n. differs from other chedimine genera by
      its unusually long and slender legs, an elongate body, a unique shape of the
      bipartite thoracic fovea, reduced leg scopulae, smaller spinnerets, and other
      characters, which are presumably apomorphic. We propose two taxonomic changes: 1)
      based on widely spaced lateral eyes the Western African genus Badia Roewer, 1961
      is transferred from Chediminae to Palpimaninae, and 2) Fernandezina gyirongensis
      Hu & Li, 1987 from China, based on palpal morphology, is transferred to the Asian
      genus Steriphopus Simon, 1887 for a new combination Steriphopus gyirongensis (Hu
      & Li, 1987) comb. n. 

PMID- 24039535
TI  - A new species and additional records of Lobrathium Mulsant & Rey (Coleoptera,
      Staphylinidae, Paederinae) from China.
AB  - Lobrathium fuscoguttatum sp. n. (type locality: Guangxi) is described and
      illustrated. The latest key to the Lobrathium species of mainland China is
      modified to include the new species. Additional data are provided for six
      previously described species. 

PMID- 24039536
TI  - Revision of the genera Hovadelium Ardoin and Mimolaena Ardoin (Coleoptera,
      Tenebrionidae, Laenini) from Madagascar, with remarks on tribal assignment.
AB  - The genera Hovadelium Ardoin, 1961 and Mimolaena Ardoin, 1961, endemic in
      Madagascar, are revised and assigned to the tribe Laenini Seidlitz, 1896
      (subfamily Lagriinae Latreille, 1825). New species: Hovadelium ardoini sp. n.,
      Hovadelium bremeri sp. n. and Mimolaena janaki sp. n. An identification key is
      compiled for all taxa. Distribution of Hovadelium (5 species) and Mimolaena (3
      species) is mapped. The congeners might be indicator species for the highly
      endangered mature forests in Madagascar. 

PMID- 24039537
TI  - New lucinid bivalves from shallow and deeper water of the Indian and West Pacific
      Oceans (Mollusca, Bivalvia, Lucinidae).
AB  - Four new species and a new genus of lucinid bivalves are described from shallow
      and deeper waters in the Indian and West Pacific Oceans. The new genus
      Scabrilucina (subfamily Lucininae) includes the little-known Scabrilucina
      victorialis (Melvill, 1899) from the Arabian Sea and Scabrilucina vitrea
      (Deshayes, 1844) from the Andaman Sea as well as a new species Scabrilucina
      melvilli from the Torres Strait off northeastern Australia. Ferrocina brunei new
      species (Lucininae) was recovered from 60 m near oil drilling activities off
      Borneo; its anatomy confirmed the presence of symbiotic bacteria. Two unusual
      deeper water species of Leucosphaerinae are described, both species included in
      on-going molecular analyses; Gonimyrtea ferruginea from 400-650 m in the
      southwest Pacific and Myrtina reflexa from 200-825 m off Zanzibar and Madagascar.

PMID- 24039538
TI  - A new genus and species of Tullbergiidae (Collembola) from the Pacific Mexican
      coast.
AB  - The new genus Mexicaphorura, and its type species Mexicaphorura guerrerensis sp.
      n. are described from marine littoral sand. The new genus is similar to
      Sensilatullbergia Thibaud & Ndiaye, 2006 in having very big sensilla on sensorial
      organ of antennal segment III, but of different shape, the kind of postantennal
      organ, with simple vesicles in Mexicaphorura versus composed vesicles in
      Sensilatullbergia and formulae of the pseudocelli. 

PMID- 24039539
TI  - Time-space Kriging to address the spatiotemporal misalignment in the large
      datasets.
AB  - This paper presents a Bayesian hierarchical spatiotemporal method of
      interpolation, termed as Markov Cube Kriging (MCK). The classical Kriging methods
      become computationally prohibitive, especially for large datasets due to the
      O(n3) matrix decomposition. MCK offers novel and computationally efficient
      solutions to address spatiotemporal misalignment, mismatch in the spatiotemporal
      scales and missing values across space and time in large spatiotemporal datasets.
      MCK is flexible in that it allows for non-separable spatiotemporal structure and
      nonstationary covariance at the hierarchical spatiotemporal scales. Employing MCK
      we developed estimates of daily concentration of fine particulates matter <=2.5
      MUm in aerodynamic diameter (PM2.5) at 2.5 km spatial grid for the Cleveland
      Metropolitan Statistical Area, 2000 to 2009. Our validation and cross-validation
      suggest that MCK achieved robust prediction of spatiotemporal random effects and
      underlying hierarchical and nonstationary spatiotemporal structure in air
      pollution data. MCK has important implications for environmental epidemiology and
      environmental sciences for exposure quantification and collocation of data from
      different sources, available at different spatiotemporal scales.

PMID- 24039540
TI  - Modeling of nanotherapeutics delivery based on tumor perfusion.
AB  - Heterogeneities in the perfusion of solid tumors prevent optimal delivery of
      nanotherapeutics. Clinical imaging protocols to obtain patient-specific data have
      proven difficult to implement. It is challenging to determine which perfusion
      features hold greater prognostic value and to relate measurements to vessel
      structure and function. With the advent of systemically administered
      nanotherapeutics, whose delivery is dependent on overcoming diffusive and
      convective barriers to transport, such knowledge is increasingly important. We
      describe a framework for the automated evaluation of vascular perfusion curves
      measured at the single vessel level. Primary tumor fragments, collected from
      triple-negative breast cancer patients and grown as xenografts in mice, were
      injected with fluorescence contrast and monitored using intravital microscopy.
      The time to arterial peak and venous delay, two features whose probability
      distributions were measured directly from time-series curves, were analyzed using
      a Fuzzy C-mean (FCM) supervised classifier in order to rank individual tumors
      according to their perfusion characteristics. The resulting rankings correlated
      inversely with experimental nanoparticle accumulation measurements, enabling
      modeling of nanotherapeutics delivery without requiring any underlying
      assumptions about tissue structure or function, or heterogeneities contained
      within. With additional calibration, these methodologies may enable the study of
      nanotherapeutics delivery strategies in a variety of tumor models.

PMID- 24039541
TI  - Black-White variations in the lagged reciprocal relationship between religiosity
      and perceived control.
AB  - This national longitudinal data-based multi-population LISREL study, the most
      comprehensive assessment to date of racial variations in the (in)congruity
      between religiosity and perceived control, gauges variation among Black and White
      Americans in the lagged reciprocal relationship between religiosity dimensions
      and mastery. Racial variation in the reciprocal religiosity-perceived control
      relationship has hitherto gone un-addressed. Prior investigations have also
      typically utilised cross-sectional samples - often from regional or age-specific
      populations. The observed public religiosity-mastery relationship over time
      exhibits signs of mutual reinforcement among Blacks: public religiosity enhances
      Blacks' subsequent mastery, while prior mastery borderline-significantly enhances
      their public religiosity. The subjective religiosity-mastery relationship among
      Whites evinces a marginally countervailing pattern: Subjective religiosity
      diminishes Whites' mastery, while mastery borderline-significantly enhances their
      subjective religiosity. The inordinately positive public religiosity-effect on
      Blacks' mastery notably constitutes solid support for the "resource compensation"
      perspective on the impact of religiosity on mastery across dominant and
      subordinate groups.

PMID- 24039542
TI  - The Political and Community Context of Immigrant Naturalization.
AB  - Becoming a citizen is a component of a larger process of immigrant incorporation
      into U.S. society. It is most often treated as an individual-level choice,
      associated with such personal characteristics as the duration of residence in the
      U.S., age, education, and language acquisition. This study uses microdata from
      Census 2000 in conjunction with other measures to examine aspects of the
      community and policy context that influence the choices made by individuals. The
      results confirm previous research on the effects of individual-level
      characteristics on attaining citizenship. There is also strong evidence of
      collective influences: both the varied political histories of immigrant groups in
      their home country and the political and community environment that they
      encounter in the U.S. have significant impacts on their propensity of
      naturalization.

PMID- 24039543
TI  - Quantum Tunnelling to the Origin and Evolution of Life.
AB  - Quantum tunnelling is a phenomenon which becomes relevant at the nanoscale and
      below. It is a paradox from the classical point of view as it enables elementary
      particles and atoms to permeate an energetic barrier without the need for
      sufficient energy to overcome it. Tunnelling might seem to be an exotic process
      only important for special physical effects and applications such as the Tunnel
      Diode, Scanning Tunnelling Microscopy (electron tunnelling) or Near-field Optical
      Microscopy operating in photon tunnelling mode. However, this review demonstrates
      that tunnelling can do far more, being of vital importance for life: physical and
      chemical processes which are crucial in theories about the origin and evolution
      of life can be traced directly back to the effects of quantum tunnelling. These
      processes include the chemical evolution in stellar interiors and within the cold
      interstellar medium, prebiotic chemistry in the atmosphere and subsurface of
      planetary bodies, planetary habitability via insolation and geothermal heat as
      well as the function of biomolecular nanomachines. This review shows that quantum
      tunnelling has many highly important implications to the field of molecular and
      biological evolution, prebiotic chemistry and astrobiology.

PMID- 24039544
TI  - Perylenequinones: Isolation, Synthesis, and Biological Activity.
AB  - The perylenequinones are a novel class of natural products characterized by
      pentacyclic conjugated chromophore giving rise to photoactivity. Potentially
      useful light-activated biological activity, targeting protein kinase C (PKC), has
      been identified for several of the natural products. Recently discovered new
      members of this class of compound, as well as several related
      phenanthroperylenequinones, are reviewed. Natural product modifications that
      improve biological profiles, and avenues for the total synthesis of analogs,
      which are not available from the natural product series, are outlined. An
      overview of structure/function relationships is provided.

PMID- 24039545
TI  - Affective responses to exercise in overweight women: Initial insight and possible
      influence on energy intake.
AB  - : It is unclear how exercise influences affect in overweight and obese
      individuals. OBJECTIVES: To examine the effect of a single exercise session on
      positive and negative affect and examine whether pre- to post-exercise changes in
      affect influence subsequent energy intake (EI). METHODS: Nineteen sedentary,
      overweight/obese women walked for ~40 minutes at a moderate-intensity on one day
      and rested for a similar duration on a separate day. Positive (PA) and negative
      affect (NA) were assessed pre-testing, post-testing, 60, and 120 minutes post
      testing using the Positive and Negative Affect Schedule. Energy intake was
      determined by measuring food intake before and after a buffet meal 1-2 hours post
      exercise/rest. RESULTS: For PA, the time x condition interaction was significant
      (p<0.05). There was a trend for those subjects with improved PA from pre to post
      exercise (58%) to consume fewer calories post-exercise (524 +/- 260.9 kcal)
      compared to post-rest (566.1 +/- 303.0 kcal), while those who had a worsening or
      no change in PA (42%) had a higher EI following exercise (588.0 +/- 233.7 kcal)
      compared to rest (524.6 +/- 281.7 kcal; p=0.08). NA was not significantly altered
      by exercise. CONCLUSIONS: Some overweight/obese individuals appear to experience
      an increase in positive affect with exercise; however, there is a high degree of
      individual variability in responses that warrants further examination. This study
      also provides initial evidence that a worsening in affect following exercise may
      unfavorably impact eating behaviors. These preliminary findings have the
      potential to enhance our understanding of factors mediating the relationship
      between exercise and EI.

PMID- 24039546
TI  - Multilingual Stroop performance: Effects of trilingualism and proficiency on
      inhibitory control.
AB  - Previous research suggests that multilinguals' languages are constantly co
      activated and that experience managing this co-activation changes inhibitory
      control function. The present study examined language interaction and inhibitory
      control using a colour-word Stroop task. Multilingual participants were tested in
      their three most proficient languages. The classic Stroop effect was detected in
      all three languages, with participants performing more accurately on congruent
      than on incongruent trials. Multilinguals were faster and more accurate in the
      within-language-competition condition than in the between-language-competition
      condition, indicating that additional processing costs are required when stimulus
      and response languages differ. Language proficiency influenced speed, accuracy
      and error patterns in multilingual Stroop task performance. These findings
      augment our understanding of language processing and inhibitory control in
      multilingual populations and suggest that experience using multiple languages
      changes demands on cognitive function.

PMID- 24039547
TI  - Predictors of Criminal Justice Outcomes Among Mental Health Courts Participants:
      The Role of Perceived Coercion and Subjective Mental Health Recovery.
AB  - Internationally, one effort to reduce the number of people with serious mental
      illness (SMI) in jails and prisons is the development of Mental Health Courts
      (MHC). Research on MHCs to date has been disproportionately focused on the study
      of recidivism and re-incarceration over the potential of these problem-solving
      courts to facilitate mental health recovery and affect the slope or gradient of
      opportunity for recovery. Despite the strong conceptual links between the MHC
      approach and the recovery-orientation in mental health, the capacity for MHCs to
      facilitate recovery has not been explored. This user-informed mental health and
      criminal justice (MH/CJ) community based participatory (CBPR) study assesses the
      extent to which MHC practices align with recovery-oriented principles and may
      subsequently affect criminal justice outcomes. We report on the experiences and
      perceptions of 51 MHC participants across four metropolitan Mental Health Courts.
      Specifically, the current study assesses: 1) how defendants' perceptions of court
      practices, particularly with regard to procedural justice and coercion, relate to
      perceptions of mental health recovery and psychiatric symptoms, and, 2) how
      perceptions of procedural justice and mental health recovery relate to subsequent
      criminal justice outcomes. The authors hypothesized that perceived coercion and
      mental health recovery would be inversely related, that perceived coercion would
      be associated with worse criminal justice outcomes, and perceptions of mental
      health recovery would be associated with better criminal justice outcomes.
      Results suggest that perceived coercion in the MHC experience was negatively
      associated with perceptions of recovery among MHC participants. Perceptions of
      "negative pressures," a component of coercion, were important predictors of
      criminal justice involvement in the 12 month period following MHC admission, even
      when controlling for other factors that were related to criminal justice
      outcomes, and that an increase in procedural justice was associated with a
      decrease in symptoms but curiously not to an increase in attitudes toward
      recovery. Implications and future directions are discussed.

PMID- 24039548
TI  - Point-of-Care Testing at the Disaster-Emergency-Critical Care Interface.
AB  - Point-of-care (POC) testing allows for medical testing to be performed across the
      disaster-emergency-critical care continuum. The disaster-emergency-critical care
      continuum begins with the identification of at-risk patients, followed by patient
      stabilization, and ultimately transfer to an alternate care facility or mobile
      hospital for comprehensive critical care. Gaps at the interfaces for each of
      these settings leads to excess mortality and morbidity. Disaster victims are at
      risk for acute myocardial infarctions, acute kidney injury (AKI), and sepsis.
      However cardiac biomarker testing, renal function testing, and multiplex rapid
      pathogen detection are often unavailable or inadequate during disasters. Cardiac
      biomarker reagents require refrigeration; traditional renal function tests (i.e.,
      serum creatinine) exhibit poor sensitivity for predicting AKI in critically ill
      patients, and culture-based pathogen detection is too slow to help initiate early
      directed antimicrobial therapy. We propose three value propositions detailing how
      rapid, POC, and environmentally hardened cardiac biomarker, AKI and multiplex
      pathogen testing harmonizes the interface between disaster, emergency, and
      critical care.

PMID- 24039549
TI  - Using Prolonged Exposure to Treat Abortion-Related Posttraumatic Stress Disorder
      in Alcohol Dependent Men: A Case Study.
AB  - Men's reactions to a partner's abortion are an understudied area. Few studies
      have examined abortion as it relates to posttraumatic stress disorder (PTSD) in
      males, and no studies have examined the use of an empirically supported
      behavioral treatment for PTSD in this population. The current case study examines
      Prolonged Exposure for the treatment of abortion-related PTSD in a 46-year old
      Caucasian male who also has alcohol dependence. The patient was involved in a
      residential substance abuse treatment program at the time of treatment. After
      receiving 12 sessions of Prolonged Exposure, the patient experienced a decrease
      in PTSD symptoms as measured by the Clinician Administered PTSD Rating Scale
      (87%) and Impact of Event Scale-Revised (85%). The results of this study suggest
      that the literature supporting Prolonged Exposure as a first-line treatment for
      PTSD can be expanded to include men needing treatment for abortion-related PTSD.
      Implications for treatment and research are discussed.

PMID- 24039550
TI  - Psychosocial Outcomes of Sexual Risk Reduction in a Brief Intervention for Urban
      African American Female Adolescents.
AB  - This article describes psychosocial outcomes of a group randomized controlled
      trial of a friendship-based HIV/STI prevention intervention grounded in the AIDS
      Risk Reduction Model (ARRM). A total of 264 African American adolescent females
      were randomized to a single-session Project ORE HIV/STI prevention intervention
      or a nutrition/exercise health promotion intervention with their friendship
      group. At posttest, Project ORE participants scored higher on knowledge of
      HIV/STI prevention and protection (p < .01), knowledge of living with HIV/STI (p
      < .01), perceived HIV risk (p < .05), perceived STI risk (p < .01), and
      intentions to use condoms for vaginal sex (p < .05). Findings suggest that a
      brief friendship-based HIV/STI prevention intervention for youth can impact ARRM
      factors that increase the ability to recognize and label risky sexual behaviors
      as problematic and promote commitment to changing high-risk behaviors.

PMID- 24039551
TI  - Modeling Structural Flexibility of Proteins with Go-Models.
AB  - Structure-based models are an efficient tool for folding studies of proteins
      since by construction their energy landscape is only minimal frustrated. However,
      their intrinsic drawback is a lack of structural flexibility as usually only one
      target structure is employed to construct the potentials. Hence, a Go-model may
      not capture differences in mutation-induced protein dynamics, if - as in the case
      of the disease-related A629P mutant of the Menkes protein ATP7A - the structural
      differences between mutant and wild type are small. In this work, we introduced
      three implementations of Go-models that take into account the flexibility of
      proteins in the NMR ensemble. Comparing the wild type and the mutant A629P of the
      75-residue large 6th domain Menkes protein, we find that these new Go-potentials
      lead to broader distributions than Go-models relying on a single member of the
      NMR-ensemble. This allows us to detect the transient unfolding of a loosely
      formed beta1beta4-sheet in the mutant protein. Our results are consistent with
      previous simulations using physical force field and an explicit solvent, and
      suggests a mechanism by which these mutations cause Menkes disease. In addition,
      the improved Go-models suggest differences in the folding pathway between wild
      type and mutant, an observation that was not accessible to simulations of this 75
      residue protein with a physical all-atom force field and explicit solvent.

PMID- 24039552
TI  - Folding and self-assembly of a small protein complex.
AB  - The synthetic homotetrameric betabetaalpha (BBAT1) protein possesses a stable
      quaternary structure with a betabetaalpha fold. Because of its small size (a
      total of 84 residues), the homotetramer is an excellent model system with which
      to study the self-assembly and protein-protein interactions. We find from replica
      exchange molecular dynamics simulations with the coarse-grain UNRES force field
      that the folding and association pathway consists of three well-separated steps,
      where that association to a tetramer precedes and facilitates folding of the four
      chains. At room temperature the tetramer exists in an ensemble of diverse
      structures. The crystal structure becomes energetically favored only when the
      molecule is put in a dense and crystal-like environment. The observed picture of
      folding promoted by association may mirror the mechanism according to which
      intrinsically unfolded proteins assume their functional structure.

PMID- 24039553
TI  - Calculating the Bending Modulus for Multicomponent Lipid Membranes in Different
      Thermodynamic Phases.
AB  - We establish a computational approach to extract the bending modulus, KC , for
      lipid membranes from relatively small-scale molecular simulations. Fluctuations
      in the splay of individual pairs of lipids faithfully inform on KC in
      multicomponent membranes over a large range of rigidities in different
      thermodynamic phases. Predictions are validated by experiments even where the
      standard spectral analysis-based methods fail. The local nature of this method
      potentially allows its extension to calculations of KC in protein-laden
      membranes.

PMID- 24039554
TI  - Variational Implicit-Solvent Modeling of Host-Guest Binding: A Case Study on
      Cucurbit[7]uril|
AB  - The synthetic host cucurbit[7]uril (CB[7]) binds aromatic guests or metal
      complexes with ultrahigh affinity compared with that typically displayed in
      protein-ligand binding. Due to its small size, CB[7] serves as an ideal receptor
      ligand system for developing computational methods for molecular recognition.
      Here, we apply the recently developed variational implicit-solvent model (VISM),
      numerically evaluated by the level-set method, to study hydration effects in the
      high-affinity binding of the B2 bicyclo[2.2.2]octane derivative to CB[7]. For the
      unbound host, we find that the host cavity favors the hydrated state over the dry
      state due to electrostatic effects. For the guest binding, we find reasonable
      agreement to experimental binding affinities. Dissection of the individual VISM
      free-energy contributions shows that the major driving forces are water-mediated
      hydrophobic interactions and the intrinsic (vacuum) host-guest van der Waals
      interactions. These findings are in line with recent experiments and molecular
      dynamics simulations with explicit solvent. It is expected that the level-set
      VISM, with further refinement on the electrostatic descriptions, can efficiently
      predict molecular binding and recognition in a wide range of future applications.

PMID- 24039555
TI  - Evaluation of a New 1H/31P Dual-Tuned Birdcage Coil for 31P Spectroscopy.
AB  - We introduce a new dual-tuned Hydrogen/Phosphorus (1H/31P) birdcage coil,
      referred to as split birdcage coil, and evaluate its performance using both
      simulations and magnetic resonance (MR) experiments on a 3 T MR scanner. The
      proposed coil simplifies the practical matters of tuning and matching, which
      makes the coil easily reproducible. Simulations were run with the Finite
      Difference in Time Domain (FDTD) method to evaluate the sensitivity and
      homogeneity of the magnetic field generated by the proposed 1H coils. Following
      simulations, MR experiments were conducted using both a phantom and human thigh
      to compare the proposed design with a currently available commercial dual-tuned
      flexible surface coil, referred to as flex surface coil, for signal to noise
      ratio (SNR) as well as homogeneity for the 31P coil. At regions deep within the
      human thigh, the split birdcage coil was able to acquire spectroscopic signal
      with a higher average SNR than the flex surface coil. For all regions except
      those close to the flex surface coil, the split birdcage coil matched or exceeded
      the performance of the flex surface coil.

PMID- 24039556
TI  - Measuring Communities of Faith: A Preliminary Investigation.
AB  - Numerous references are made in the literature to communities of faith, yet there
      have been relatively few efforts to measure them empirically. The purpose of this
      study is to address this gap in the literature by estimating a higher-order
      confirmatory factor model that consists of two tiers. Seven dimensions of church
      based social support make up the first tier: emotional support received from rank
      and-file church members, emotional support given to fellow church members,
      tangible support received from rank-and-file church members, tangible support
      given to fellow congregants, spiritual support received from fellow church
      members, emotional support received from a pastor, and tangible support received
      from a pastor. It is hypothesized that these first-order constructs are driven by
      a higher-order latent variable that denotes a community of faith. Data from a
      nationwide survey reveal that, for the sample taken as a whole, emotional support
      represents the way in which a community of faith is most likely to be manifest
      while tangible support is a less critical component. Moreover, the results
      indicate that a community of faith is more likely to reside in support exchanged
      among rank-and-file church members than support received from a pastor.

PMID- 24039557
TI  - The Crisis Intervention Team Model of Police Response to Mental Health Crises: A
      Primer for Mental Health Practitioners.
AB  - As persons with mental illnesses and law enforcement become increasingly
      entangled, the collaboration of police and mental health service providers has
      become critical to appropriately serving the needs of individuals experiencing
      mental health crises. This article introduces the Crisis Intervention Team (CIT)
      Model as a collaborative approach to safely and effectively address the needs of
      persons with mental illnesses, link them to appropriate services, and divert them
      from the criminal justice system if appropriate. We discuss the key elements of
      the CIT model, implementation and its related challenges, as well as variations
      of the model. While this model has not undergone enough research to be deemed an
      Evidence-Based Practice, it has been successfully utilized in many law
      enforcement agencies worldwide and is considered a "Best Practice" model in law
      enforcement. This primer for mental health practitioners serves as an
      introduction to a model that may already be utilized in their community or serve
      as a springboard for the development CIT programs where they do not currently
      exist.

PMID- 24039558
TI  - Finding associations among histone modifications using sparse partial correlation
      networks.
AB  - Histone modifications are known to play an important role in the regulation of
      transcription. While individual modifications have received much attention in
      genome-wide analyses, little is known about their relationships. Some authors
      have built Bayesian networks of modifications, however most often they have used
      discretized data, and relied on unrealistic assumptions such as the absence of
      feedback mechanisms or hidden confounding factors. Here, we propose to infer
      undirected networks based on partial correlations between histone modifications.
      Within the partial correlation framework, correlations among two variables are
      controlled for associations induced by the other variables. Partial correlation
      networks thus focus on direct associations of histone modifications. We apply
      this methodology to data in CD4+ cells. The resulting network is well supported
      by common knowledge. When pairs of modifications show a large difference between
      their correlation and their partial correlation, a potential confounding factor
      is identified and provided as explanation. Data from different cell types (IMR90,
      H1) is also exploited in the analysis to assess the stability of the networks.
      The results are remarkably similar across cell types. Based on this observation,
      the networks from the three cell types are integrated into a consensus network to
      increase robustness. The data and the results discussed in the manuscript can be
      found, together with code, on http://spcn.molgen.mpg.de/index.html. 

PMID- 24039559
TI  - Distal loop flexibility of a regulatory domain modulates dynamics and activity of
      C-terminal SRC kinase (csk).
AB  - The Src family of tyrosine kinases (SFKs) regulate numerous aspects of cell
      growth and differentiation and are under the principal control of the C-terminal
      Src Kinase (Csk). Csk and SFKs share a modular design with the kinase domain
      downstream of the N-terminal SH2 and SH3 domains that regulate catalytic function
      and membrane localization. While the function of interfacial segments in these
      multidomain kinases are well-investigated, little is known about how surface
      sites and long-range, allosteric coupling control protein dynamics and catalytic
      function. The SH2 domain of Csk is an essential component for the down-regulation
      of all SFKs. A unique feature of the SH2 domain of Csk is the tight turn in place
      of the canonical CD loop in a surface site far removed from kinase domain
      interactions. In this study, we used a combination of experimental and
      computational methods to probe the importance of this difference by constructing
      a Csk variant with a longer SH2 CD loop to mimic the flexibility found in
      homologous kinase SH2 domains. Our results indicate that while the fold and
      function of the isolated domain and the full-length kinase are not affected by
      loop elongation, native protein dynamics that are essential for efficient
      catalysis are perturbed. We also identify key motifs and routes through which the
      distal SH2 site might influence catalysis at the active site. This study
      underscores the sensitivity of intramolecular signaling and catalysis to native
      protein dynamics that arise from modest changes in allosteric regions while
      providing a potential strategy to alter intrinsic activity and signaling
      modulation. 

PMID- 24039560
TI  - Genome-wide signatures of transcription factor activity: connecting transcription
      factors, disease, and small molecules.
AB  - Identifying transcription factors (TF) involved in producing a genome-wide
      transcriptional profile is an essential step in building mechanistic model that
      can explain observed gene expression data. We developed a statistical framework
      for constructing genome-wide signatures of TF activity, and for using such
      signatures in the analysis of gene expression data produced by complex
      transcriptional regulatory programs. Our framework integrates ChIP-seq data and
      appropriately matched gene expression profiles to identify True REGulatory (TREG)
      TF-gene interactions. It provides genome-wide quantification of the likelihood of
      regulatory TF-gene interaction that can be used to either identify regulated
      genes, or as genome-wide signature of TF activity. To effectively use ChIP-seq
      data, we introduce a novel statistical model that integrates information from all
      binding "peaks" within 2 Mb window around a gene's transcription start site
      (TSS), and provides gene-level binding scores and probabilities of regulatory
      interaction. In the second step we integrate these binding scores and regulatory
      probabilities with gene expression data to assess the likelihood of True
      REGulatory (TREG) TF-gene interactions. We demonstrate the advantages of TREG
      framework in identifying genes regulated by two TFs with widely different
      distribution of functional binding events (ERalpha and E2f1). We also show that
      TREG signatures of TF activity vastly improve our ability to detect involvement
      of ERalpha in producing complex diseases-related transcriptional profiles.
      Through a large study of disease-related transcriptional signatures and
      transcriptional signatures of drug activity, we demonstrate that increase in
      statistical power associated with the use of TREG signatures makes the crucial
      difference in identifying key targets for treatment, and drugs to use for
      treatment. All methods are implemented in an open-source R package treg. The
      package also contains all data used in the analysis including 494 TREG binding
      profiles based on ENCODE ChIP-seq data. The treg package can be downloaded at
      http://GenomicsPortals.org. 

PMID- 24039561
TI  - Detecting and removing inconsistencies between experimental data and signaling
      network topologies using integer linear programming on interaction graphs.
AB  - Cross-referencing experimental data with our current knowledge of signaling
      network topologies is one central goal of mathematical modeling of cellular
      signal transduction networks. We present a new methodology for data-driven
      interrogation and training of signaling networks. While most published methods
      for signaling network inference operate on Bayesian, Boolean, or ODE models, our
      approach uses integer linear programming (ILP) on interaction graphs to encode
      constraints on the qualitative behavior of the nodes. These constraints are posed
      by the network topology and their formulation as ILP allows us to predict the
      possible qualitative changes (up, down, no effect) of the activation levels of
      the nodes for a given stimulus. We provide four basic operations to detect and
      remove inconsistencies between measurements and predicted behavior: (i) find a
      topology-consistent explanation for responses of signaling nodes measured in a
      stimulus-response experiment (if none exists, find the closest explanation); (ii)
      determine a minimal set of nodes that need to be corrected to make an
      inconsistent scenario consistent; (iii) determine the optimal subgraph of the
      given network topology which can best reflect measurements from a set of
      experimental scenarios; (iv) find possibly missing edges that would improve the
      consistency of the graph with respect to a set of experimental scenarios the
      most. We demonstrate the applicability of the proposed approach by interrogating
      a manually curated interaction graph model of EGFR/ErbB signaling against a
      library of high-throughput phosphoproteomic data measured in primary hepatocytes.
      Our methods detect interactions that are likely to be inactive in hepatocytes and
      provide suggestions for new interactions that, if included, would significantly
      improve the goodness of fit. Our framework is highly flexible and the underlying
      model requires only easily accessible biological knowledge. All related
      algorithms were implemented in a freely available toolbox SigNetTrainer making it
      an appealing approach for various applications. 

PMID- 24039562
TI  - Motility enhancement through surface modification is sufficient for
      cyanobacterial community organization during phototaxis.
AB  - The emergent behaviors of communities of genotypically identical cells cannot be
      easily predicted from the behaviors of individual cells. In many cases, it is
      thought that direct cell-cell communication plays a critical role in the
      transition from individual to community behaviors. In the unicellular
      photosynthetic cyanobacterium Synechocystis sp. PCC 6803, individual cells
      exhibit light-directed motility ("phototaxis") over surfaces, resulting in the
      emergence of dynamic spatial organization of multicellular communities. To probe
      this striking community behavior, we carried out time-lapse video microscopy
      coupled with quantitative analysis of single-cell dynamics under varying light
      conditions. These analyses suggest that cells secrete an extracellular substance
      that modifies the physical properties of the substrate, leading to enhanced
      motility and the ability for groups of cells to passively guide one another. We
      developed a biophysical model that demonstrates that this form of indirect,
      surface-based communication is sufficient to create distinct motile groups whose
      shape, velocity, and dynamics qualitatively match our experimental observations,
      even in the absence of direct cellular interactions or changes in single-cell
      behavior. Our computational analysis of the predicted community behavior, across
      a matrix of cellular concentrations and light biases, demonstrates that spatial
      patterning follows robust scaling laws and provides a useful resource for the
      generation of testable hypotheses regarding phototactic behavior. In addition, we
      predict that degradation of the surface modification may account for the
      secondary patterns occasionally observed after the initial formation of a
      community structure. Taken together, our modeling and experiments provide a
      framework to show that the emergent spatial organization of phototactic
      communities requires modification of the substrate, and this form of surface
      based communication could provide insight into the behavior of a wide array of
      biological communities. 

PMID- 24039563
TI  - Spike triggered covariance in strongly correlated gaussian stimuli.
AB  - Many biological systems perform computations on inputs that have very large
      dimensionality. Determining the relevant input combinations for a particular
      computation is often key to understanding its function. A common way to find the
      relevant input dimensions is to examine the difference in variance between the
      input distribution and the distribution of inputs associated with certain
      outputs. In systems neuroscience, the corresponding method is known as spike
      triggered covariance (STC). This method has been highly successful in
      characterizing relevant input dimensions for neurons in a variety of sensory
      systems. So far, most studies used the STC method with weakly correlated Gaussian
      inputs. However, it is also important to use this method with inputs that have
      long range correlations typical of the natural sensory environment. In such
      cases, the stimulus covariance matrix has one (or more) outstanding eigenvalues
      that cannot be easily equalized because of sampling variability. Such outstanding
      modes interfere with analyses of statistical significance of candidate input
      dimensions that modulate neuronal outputs. In many cases, these modes obscure the
      significant dimensions. We show that the sensitivity of the STC method in the
      regime of strongly correlated inputs can be improved by an order of magnitude or
      more. This can be done by evaluating the significance of dimensions in the
      subspace orthogonal to the outstanding mode(s). Analyzing the responses of
      retinal ganglion cells probed with [Formula: see text] Gaussian noise, we find
      that taking into account outstanding modes is crucial for recovering relevant
      input dimensions for these neurons. 

PMID- 24039564
TI  - Semi-automated curation of metabolic models via flux balance analysis: a case
      study with Mycoplasma gallisepticum.
AB  - Primarily used for metabolic engineering and synthetic biology, genome-scale
      metabolic modeling shows tremendous potential as a tool for fundamental research
      and curation of metabolism. Through a novel integration of flux balance analysis
      and genetic algorithms, a strategy to curate metabolic networks and facilitate
      identification of metabolic pathways that may not be directly inferable solely
      from genome annotation was developed. Specifically, metabolites involved in
      unknown reactions can be determined, and potentially erroneous pathways can be
      identified. The procedure developed allows for new fundamental insight into
      metabolism, as well as acting as a semi-automated curation methodology for genome
      scale metabolic modeling. To validate the methodology, a genome-scale metabolic
      model for the bacterium Mycoplasma gallisepticum was created. Several reactions
      not predicted by the genome annotation were postulated and validated via the
      literature. The model predicted an average growth rate of 0.358+/-0.12[Formula:
      see text], closely matching the experimentally determined growth rate of M.
      gallisepticum of 0.244+/-0.03[Formula: see text]. This work presents a powerful
      algorithm for facilitating the identification and curation of previously known
      and new metabolic pathways, as well as presenting the first genome-scale
      reconstruction of M. gallisepticum. 

PMID- 24039565
TI  - Antimicrobial peptides design by evolutionary multiobjective optimization.
AB  - Antimicrobial peptides (AMPs) are an abundant and wide class of molecules
      produced by many tissues and cell types in a variety of mammals, plant and animal
      species. Linear alpha-helical antimicrobial peptides are among the most
      widespread membrane-disruptive AMPs in nature, representing a particularly
      successful structural arrangement in innate defense. Recently, AMPs have received
      increasing attention as potential therapeutic agents, owing to their broad
      activity spectrum and their reduced tendency to induce resistance. The
      introduction of non-natural amino acids will be a key requisite in order to
      contrast host resistance and increase compound's life. In this work, the
      possibility to design novel AMP sequences with non-natural amino acids was
      achieved through a flexible computational approach, based on chemophysical
      profiles of peptide sequences. Quantitative structure-activity relationship
      (QSAR) descriptors were employed to code each peptide and train two statistical
      models in order to account for structural and functional properties of alpha
      helical amphipathic AMPs. These models were then used as fitness functions for a
      multi-objective evolutional algorithm, together with a set of constraints for the
      design of a series of candidate AMPs. Two ab-initio natural peptides were
      synthesized and experimentally validated for antimicrobial activity, together
      with a series of control peptides. Furthermore, a well-known Cecropin-Mellitin
      alpha helical antimicrobial hybrid (CM18) was optimized by shortening its amino
      acid sequence while maintaining its activity and a peptide with non-natural amino
      acids was designed and tested, demonstrating the higher activity achievable with
      artificial residues. 

PMID- 24039566
TI  - Mammalian rest/activity patterns explained by physiologically based modeling.
AB  - Circadian rhythms are fundamental to life. In mammals, these rhythms are
      generated by pacemaker neurons in the suprachiasmatic nucleus (SCN) of the
      hypothalamus. The SCN is remarkably consistent in structure and function between
      species, yet mammalian rest/activity patterns are extremely diverse, including
      diurnal, nocturnal, and crepuscular behaviors. Two mechanisms have been proposed
      to account for this diversity: (i) modulation of SCN output by downstream nuclei,
      and (ii) direct effects of light on activity. These two mechanisms are difficult
      to disentangle experimentally and their respective roles remain unknown. To
      address this, we developed a computational model to simulate the two mechanisms
      and their influence on temporal niche. In our model, SCN output is relayed via
      the subparaventricular zone (SPZ) to the dorsomedial hypothalamus (DMH), and
      thence to ventrolateral preoptic nuclei (VLPO) and lateral hypothalamus (LHA).
      Using this model, we generated rich phenotypes that closely resemble experimental
      data. Modulation of SCN output at the SPZ was found to generate a full spectrum
      of diurnal-to-nocturnal phenotypes. Intriguingly, we also uncovered a novel
      mechanism for crepuscular behavior: if DMH/VLPO and DMH/LHA projections act
      cooperatively, daily activity is unimodal, but if they act competitively,
      activity can become bimodal. In addition, we successfully reproduced
      diurnal/nocturnal switching in the rodent Octodon degu using coordinated
      inversions in both masking and circadian modulation. Finally, the model correctly
      predicted the SCN lesion phenotype in squirrel monkeys: loss of circadian
      rhythmicity and emergence of ~4-h sleep/wake cycles. In capturing these diverse
      phenotypes, the model provides a powerful new framework for understanding
      rest/activity patterns and relating them to underlying physiology. Given the
      ubiquitous effects of temporal organization on all aspects of animal behavior and
      physiology, this study sheds light on the physiological changes required to
      orchestrate adaptation to various temporal niches. 

PMID- 24039567
TI  - The next generation of transcription factor binding site prediction.
AB  - Finding where transcription factors (TFs) bind to the DNA is of key importance to
      decipher gene regulation at a transcriptional level. Classically, computational
      prediction of TF binding sites (TFBSs) is based on basic position weight matrices
      (PWMs) which quantitatively score binding motifs based on the observed nucleotide
      patterns in a set of TFBSs for the corresponding TF. Such models make the strong
      assumption that each nucleotide participates independently in the corresponding
      DNA-protein interaction and do not account for flexible length motifs. We
      introduce transcription factor flexible models (TFFMs) to represent TF binding
      properties. Based on hidden Markov models, TFFMs are flexible, and can model both
      position interdependence within TFBSs and variable length motifs within a single
      dedicated framework. The availability of thousands of experimentally validated
      DNA-TF interaction sequences from ChIP-seq allows for the generation of models
      that perform as well as PWMs for stereotypical TFs and can improve performance
      for TFs with flexible binding characteristics. We present a new graphical
      representation of the motifs that convey properties of position interdependence.
      TFFMs have been assessed on ChIP-seq data sets coming from the ENCODE project,
      revealing that they can perform better than both PWMs and the dinucleotide weight
      matrix extension in discriminating ChIP-seq from background sequences. Under the
      assumption that ChIP-seq signal values are correlated with the affinity of the TF
      DNA binding, we find that TFFM scores correlate with ChIP-seq peak signals.
      Moreover, using available TF-DNA affinity measurements for the Max TF, we
      demonstrate that TFFMs constructed from ChIP-seq data correlate with published
      experimentally measured DNA-binding affinities. Finally, TFFMs allow for the
      straightforward computation of an integrated TF occupancy score across a
      sequence. These results demonstrate the capacity of TFFMs to accurately model DNA
      protein interactions, while providing a single unified framework suitable for the
      next generation of TFBS prediction. 

PMID- 24039568
TI  - From cellular characteristics to disease diagnosis: uncovering phenotypes with
      supercells.
AB  - Cell heterogeneity and the inherent complexity due to the interplay of multiple
      molecular processes within the cell pose difficult challenges for current single
      cell biology. We introduce an approach that identifies a disease phenotype from
      multiparameter single-cell measurements, which is based on the concept of
      "supercell statistics", a single-cell-based averaging procedure followed by a
      machine learning classification scheme. We are able to assess the optimal
      tradeoff between the number of single cells averaged and the number of
      measurements needed to capture phenotypic differences between healthy and
      diseased patients, as well as between different diseases that are difficult to
      diagnose otherwise. We apply our approach to two kinds of single-cell datasets,
      addressing the diagnosis of a premature aging disorder using images of cell
      nuclei, as well as the phenotypes of two non-infectious uveitides (the ocular
      manifestations of Behcet's disease and sarcoidosis) based on multicolor flow
      cytometry. In the former case, one nuclear shape measurement taken over a group
      of 30 cells is sufficient to classify samples as healthy or diseased, in
      agreement with usual laboratory practice. In the latter, our method is able to
      identify a minimal set of 5 markers that accurately predict Behcet's disease and
      sarcoidosis. This is the first time that a quantitative phenotypic distinction
      between these two diseases has been achieved. To obtain this clear phenotypic
      signature, about one hundred CD8(+) T cells need to be measured. Although the
      molecular markers identified have been reported to be important players in
      autoimmune disorders, this is the first report pointing out that CD8(+) T cells
      can be used to distinguish two systemic inflammatory diseases. Beyond these
      specific cases, the approach proposed here is applicable to datasets generated by
      other kinds of state-of-the-art and forthcoming single-cell technologies, such as
      multidimensional mass cytometry, single-cell gene expression, and single-cell
      full genome sequencing techniques. 

PMID- 24039570
TI  - Atomic force microscopy: a new look at pathogens.

PMID- 24039569
TI  - Characterizing changes in the rate of protein-protein dissociation upon interface
      mutation using hotspot energy and organization.
AB  - Predicting the effects of mutations on the kinetic rate constants of protein
      protein interactions is central to both the modeling of complex diseases and the
      design of effective peptide drug inhibitors. However, while most studies have
      concentrated on the determination of association rate constants, dissociation
      rates have received less attention. In this work we take a novel approach by
      relating the changes in dissociation rates upon mutation to the energetics and
      architecture of hotspots and hotregions, by performing alanine scans pre- and
      post-mutation. From these scans, we design a set of descriptors that capture the
      change in hotspot energy and distribution. The method is benchmarked on 713
      kinetically characterized mutations from the SKEMPI database. Our investigations
      show that, with the use of hotspot descriptors, energies from single-point
      alanine mutations may be used for the estimation of off-rate mutations to any
      residue type and also multi-point mutations. A number of machine learning models
      are built from a combination of molecular and hotspot descriptors, with the best
      models achieving a Pearson's Correlation Coefficient of 0.79 with experimental
      off-rates and a Matthew's Correlation Coefficient of 0.6 in the detection of rare
      stabilizing mutations. Using specialized feature selection models we identify
      descriptors that are highly specific and, conversely, broadly important to
      predicting the effects of different classes of mutations, interface regions and
      complexes. Our results also indicate that the distribution of the critical
      stability regions across protein-protein interfaces is a function of complex size
      more strongly than interface area. In addition, mutations at the rim are critical
      for the stability of small complexes, but consistently harder to characterize.
      The relationship between hotregion size and the dissociation rate is also
      investigated and, using hotspot descriptors which model cooperative effects
      within hotregions, we show how the contribution of hotregions of different sizes,
      changes under different cooperative effects. 

PMID- 24039571
TI  - Bringing culture to the uncultured: Coxiella burnetii and lessons for obligate
      intracellular bacterial pathogens.

PMID- 24039572
TI  - A comprehensive analysis of in vitro and in vivo genetic fitness of Pseudomonas
      aeruginosa using high-throughput sequencing of transposon libraries.
AB  - High-throughput sequencing of transposon (Tn) libraries created within entire
      genomes identifies and quantifies the contribution of individual genes and
      operons to the fitness of organisms in different environments. We used insertion
      sequencing (INSeq) to analyze the contribution to fitness of all non-essential
      genes in the chromosome of Pseudomonas aeruginosa strain PA14 based on a library
      of ~300,000 individual Tn insertions. In vitro growth in LB provided a baseline
      for comparison with the survival of the Tn insertion strains following 6 days of
      colonization of the murine gastrointestinal tract as well as a comparison with Tn
      inserts subsequently able to systemically disseminate to the spleen following
      induction of neutropenia. Sequencing was performed following DNA extraction from
      the recovered bacteria, digestion with the MmeI restriction enzyme that
      hydrolyzes DNA 16 bp away from the end of the Tn insert, and fractionation into
      oligonucleotides of 1,200-1,500 bp that were prepared for high-throughput
      sequencing. Changes in frequency of Tn inserts into the P. aeruginosa genome were
      used to quantify in vivo fitness resulting from loss of a gene. 636 genes had <10
      sequencing reads in LB, thus defined as unable to grow in this medium. During in
      vivo infection there were major losses of strains with Tn inserts in almost all
      known virulence factors, as well as respiration, energy utilization, ion pumps,
      nutritional genes and prophages. Many new candidates for virulence factors were
      also identified. There were consistent changes in the recovery of Tn inserts in
      genes within most operons and Tn insertions into some genes enhanced in vivo
      fitness. Strikingly, 90% of the non-essential genes were required for in vivo
      survival following systemic dissemination during neutropenia. These experiments
      resulted in the identification of the P. aeruginosa strain PA14 genes necessary
      for optimal survival in the mucosal and systemic environments of a mammalian
      host. 

PMID- 24039573
TI  - Proteomic screening of human targets of viral microRNAs reveals functions
      associated with immune evasion and angiogenesis.
AB  - Kaposi's sarcoma (KS) is caused by infection with Kaposi's sarcoma-associated
      herpesvirus (KSHV). The virus expresses unique microRNAs (miRNAs), but the
      targets and functions of these miRNAs are not completely understood. In order to
      identify human targets of viral miRNAs, we measured protein expression changes
      caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in
      cell culture (pSILAC) in primary endothelial cells. This led to the
      identification of multiple human genes that are repressed at the protein level,
      but not at the miRNA level. Further analysis also identified that KSHV miRNAs can
      modulate activity or expression of upstream regulatory factors, resulting in
      suppressed activation of a protein involved in leukocyte recruitment (ICAM1)
      following lysophosphatidic acid treatment, as well as up-regulation of a pro
      angiogenic protein (HIF1alpha), and up-regulation of a protein involved in
      stimulating angiogenesis (HMOX1). This study aids in our understanding of miRNA
      mechanisms of repression and miRNA contributions to viral pathogenesis. 

PMID- 24039574
TI  - Viral membrane fusion and nucleocapsid delivery into the cytoplasm are distinct
      events in some flaviviruses.
AB  - Flaviviruses deliver their genome into the cell by fusing the viral lipid
      membrane to an endosomal membrane. The sequence and kinetics of the steps
      required for nucleocapsid delivery into the cytoplasm remain unclear. Here we
      dissect the cell entry pathway of virions and virus-like particles from two
      flaviviruses using single-particle tracking in live cells, a biochemical membrane
      fusion assay and virus infectivity assays. We show that the virus particles fuse
      with a small endosomal compartment in which the nucleocapsid remains trapped for
      several minutes. Endosomal maturation inhibitors inhibit infectivity but not
      membrane fusion. We propose a flavivirus cell entry mechanism in which the virus
      particles fuse preferentially with small endosomal carrier vesicles and depend on
      back-fusion of the vesicles with the late endosomal membrane to deliver the
      nucleocapsid into the cytoplasm. Virus entry modulates intracellular calcium
      release and phosphatidylinositol-3-phosphate kinase signaling. Moreover, the
      broadly cross-reactive therapeutic antibody scFv11 binds to virus-like particles
      and inhibits fusion. 

PMID- 24039575
TI  - The zebrafish as a new model for the in vivo study of Shigella flexneri
      interaction with phagocytes and bacterial autophagy.
AB  - Autophagy, an ancient and highly conserved intracellular degradation process, is
      viewed as a critical component of innate immunity because of its ability to
      deliver cytosolic bacteria to the lysosome. However, the role of bacterial
      autophagy in vivo remains poorly understood. The zebrafish (Danio rerio) has
      emerged as a vertebrate model for the study of infections because it is optically
      accessible at the larval stages when the innate immune system is already
      functional. Here, we have characterized the susceptibility of zebrafish larvae to
      Shigella flexneri, a paradigm for bacterial autophagy, and have used this model
      to study Shigella-phagocyte interactions in vivo. Depending on the dose, S.
      flexneri injected in zebrafish larvae were either cleared in a few days or
      resulted in a progressive and ultimately fatal infection. Using high resolution
      live imaging, we found that S. flexneri were rapidly engulfed by macrophages and
      neutrophils; moreover we discovered a scavenger role for neutrophils in
      eliminating infected dead macrophages and non-immune cell types that failed to
      control Shigella infection. We observed that intracellular S. flexneri could
      escape to the cytosol, induce septin caging and be targeted to autophagy in vivo.
      Depletion of p62 (sequestosome 1 or SQSTM1), an adaptor protein critical for
      bacterial autophagy in vitro, significantly increased bacterial burden and host
      susceptibility to infection. These results show the zebrafish larva as a new
      model for the study of S. flexneri interaction with phagocytes, and the
      manipulation of autophagy for anti-bacterial therapy in vivo. 

PMID- 24039576
TI  - Identification of immune and viral correlates of norovirus protective immunity
      through comparative study of intra-cluster norovirus strains.
AB  - Whether or not primary norovirus infections induce protective immunity has become
      a controversial issue, potentially confounded by the comparison of data from
      genetically distinct norovirus strains. Early human volunteer studies performed
      with a norovirus-positive inoculum initially led to the conclusion that primary
      infection does not generate long-term, protective immunity. More recently though,
      the epidemiological pattern of norovirus pandemics has led to the extrapolation
      that primary norovirus infection induces herd immunity. While these are seemingly
      discordant observations, they may in fact reflect virus strain-, cluster-, or
      genogroup-specific differences in protective immunity induction. Here, we report
      that highly genetically related intra-cluster murine norovirus strains differ
      dramatically in their ability to induce a protective immune response: Primary MNV
      3 infection induced robust and cross-reactive protection, whereas primary MNV-1
      infection induced modest homotypic and no heterotypic protection. In addition to
      this fundamental observation that intra-cluster norovirus strains display
      remarkable differences in protective immunity induction, we report three
      additional important observations relevant to norovirus:host interactions. First,
      antibody and CD4+ T cells are essential to controlling secondary norovirus
      infections. Second, the viral minor structural protein VP2 regulates the
      maturation of antigen presenting cells and protective immunity induction in a
      virus strain-specific manner, pointing to a mechanism by which MNV-1 may prevent
      the stimulation of memory immune responses. Third, VF1-mediated regulation of
      cytokine induction also correlates with protective immunity induction. Thus, two
      highly genetically-related norovirus strains displayed striking differences in
      induction of protective immune responses, strongly suggesting that the
      interpretation of norovirus immunity and vaccine studies must consider potential
      virus strain-specific effects. Moreover, we have identified immune (antibody and
      CD4+ T cells) and viral (VP2 and possibly VF1) correlates of norovirus protective
      immunity. These findings have significant implications for our understanding of
      norovirus immunity during primary infections as well as the development of new
      norovirus vaccines.

PMID- 24039577
TI  - Emergence of the Middle East respiratory syndrome coronavirus.

PMID- 24039578
TI  - Midcell recruitment of the DNA uptake and virulence nuclease, EndA, for
      pneumococcal transformation.
AB  - Genetic transformation, in which cells internalize exogenous DNA and integrate it
      into their chromosome, is widespread in the bacterial kingdom. It involves a
      specialized membrane-associated machinery for binding double-stranded (ds) DNA
      and uptake of single-stranded (ss) fragments. In the human pathogen Streptococcus
      pneumoniae, this machinery is specifically assembled at competence. The EndA
      nuclease, a constitutively expressed virulence factor, is recruited during
      competence to play the key role of converting dsDNA into ssDNA for uptake. Here
      we use fluorescence microscopy to show that EndA is uniformly distributed in the
      membrane of noncompetent cells and relocalizes at midcell during competence. This
      recruitment requires the dsDNA receptor ComEA. We also show that under 'static'
      binding conditions, i.e., in cells impaired for uptake, EndA and ComEA colocalize
      at midcell, together with fluorescent end-labelled dsDNA (Cy3-dsDNA). We conclude
      that midcell clustering of EndA reflects its recruitment to the DNA uptake
      machinery rather than its sequestration away from this machinery to protect
      transforming DNA from extensive degradation. In contrast, a fraction of ComEA
      molecules were located at cell poles post-competence, suggesting the pole as the
      site of degradation of the dsDNA receptor. In uptake-proficient cells, we used
      Cy3-dsDNA molecules enabling expression of a GFP fusion upon chromosomal
      integration to identify transformed cells as GFP producers 60-70 min after
      initial contact between DNA and competent cells. Recording of images since
      initial cell-DNA contact allowed us to look back to the uptake period for these
      transformed cells. Cy3-DNA foci were thus detected at the cell surface 10-11 min
      post-initial contact, all exclusively found at midcell, strongly suggesting that
      active uptake of transforming DNA takes place at this position in pneumococci. We
      discuss how midcell uptake could influence homology search, and the likelihood
      that midcell uptake is characteristic of cocci and/or the growth phase-dependency
      of competence. 

PMID- 24039579
TI  - Multicellular bacteria deploy the type VI secretion system to preemptively strike
      neighboring cells.
AB  - The Type VI Secretion System (T6SS) functions in bacteria as a contractile
      nanomachine that punctures and delivers lethal effectors to a target cell.
      Virtually nothing is known about the lifestyle or physiology that dictates when
      bacteria normally produce their T6SS, which prevents a clear understanding of how
      bacteria benefit from its action in their natural habitat. Proteus mirabilis
      undergoes a characteristic developmental process to coordinate a multicellular
      swarming behavior and will discriminate itself from another Proteus isolate
      during swarming, resulting in a visible boundary termed a Dienes line. Using
      transposon mutagenesis, we discovered that this recognition phenomenon requires
      the lethal action of the T6SS. All mutants identified in the genetic screen had
      insertions within a single 33.5-kb region that encodes a T6SS and cognate Hcp
      VrgG-linked effectors. The identified T6SS and primary effector operons were
      characterized by killing assays, by construction of additional mutants, by
      complementation, and by examining the activity of the type VI secretion system in
      real-time using live-cell microscopy on opposing swarms. We show that lethal T6SS
      dependent activity occurs when a dominant strain infiltrates deeply beyond the
      boundary of the two swarms. Using this multicellular model, we found that social
      recognition in bacteria, underlying killing, and immunity to killing all require
      cell-cell contact, can be assigned to specific genes, and are dependent on the
      T6SS. The ability to survive a lethal T6SS attack equates to "recognition". In
      contrast to the current model of T6SS being an offensive or defensive weapon our
      findings support a preemptive mechanism by which an entire population
      indiscriminately uses the T6SS for contact-dependent delivery of effectors during
      its cooperative mode of growth. 

PMID- 24039580
TI  - RIG-I and MDA-5 detection of viral RNA-dependent RNA polymerase activity
      restricts positive-strand RNA virus replication.
AB  - Type I interferons (IFN) are important for antiviral responses. Melanoma
      differentiation-associated gene 5 (MDA-5) and retinoic acid-induced gene I (RIG
      I) proteins detect cytosolic double-stranded RNA (dsRNA) or 5'-triphosphate (5'
      ppp) RNA and mediate IFN production. Cytosolic 5'-ppp RNA and dsRNA are generated
      during viral RNA replication and transcription by viral RNA replicases [RNA
      dependent RNA polymerases (RdRp)]. Here, we show that the Semliki Forest virus
      (SFV) RNA replicase can induce IFN-beta independently of viral RNA replication
      and transcription. The SFV replicase converts host cell RNA into 5'-ppp dsRNA and
      induces IFN-beta through the RIG-I and MDA-5 pathways. Inactivation of the SFV
      replicase RdRp activity prevents IFN-beta induction. These IFN-inducing modified
      host cell RNAs are abundantly produced during both wild-type SFV and its non
      pathogenic mutant infection. Furthermore, in contrast to the wild-type SFV
      replicase a non-pathogenic mutant replicase triggers increased IFN-beta
      production, which leads to a shutdown of virus replication. These results suggest
      that host cells can restrict RNA virus replication by detecting the products of
      unspecific viral replicase RdRp activity. 

PMID- 24039581
TI  - Vibrio cholerae evades neutrophil extracellular traps by the activity of two
      extracellular nucleases.
AB  - The Gram negative bacterium Vibrio cholerae is the causative agent of the
      secretory diarrheal disease cholera, which has traditionally been classified as a
      noninflammatory disease. However, several recent reports suggest that a V.
      cholerae infection induces an inflammatory response in the gastrointestinal tract
      indicated by recruitment of innate immune cells and increase of inflammatory
      cytokines. In this study, we describe a colonization defect of a double
      extracellular nuclease V. cholerae mutant in immunocompetent mice, which is not
      evident in neutropenic mice. Intrigued by this observation, we investigated the
      impact of neutrophils, as a central part of the innate immune system, on the
      pathogen V. cholerae in more detail. Our results demonstrate that V. cholerae
      induces formation of neutrophil extracellular traps (NETs) upon contact with
      neutrophils, while V. cholerae in return induces the two extracellular nucleases
      upon presence of NETs. We show that the V. cholerae wild type rapidly degrades
      the DNA component of the NETs by the combined activity of the two extracellular
      nucleases Dns and Xds. In contrast, NETs exhibit prolonged stability in presence
      of the double nuclease mutant. Finally, we demonstrate that Dns and Xds mediate
      evasion of V. cholerae from NETs and lower the susceptibility for extracellular
      killing in the presence of NETs. This report provides a first comprehensive
      characterization of the interplay between neutrophils and V. cholerae along with
      new evidence that the innate immune response impacts the colonization of V.
      cholerae in vivo. A limitation of this study is an inability for technical and
      physiological reasons to visualize intact NETs in the intestinal lumen of
      infected mice, but we can hypothesize that extracellular nuclease production by
      V. cholerae may enhance survival fitness of the pathogen through NET degradation.

PMID- 24039582
TI  - Real-time whole-body visualization of Chikungunya Virus infection and host
      interferon response in zebrafish.
AB  - Chikungunya Virus (CHIKV), a re-emerging arbovirus that may cause severe disease,
      constitutes an important public health problem. Herein we describe a novel CHIKV
      infection model in zebrafish, where viral spread was live-imaged in the whole
      body up to cellular resolution. Infected cells emerged in various organs in one
      principal wave with a median appearance time of ~14 hours post infection. Timing
      of infected cell death was organ dependent, leading to a shift of CHIKV
      localization towards the brain. As in mammals, CHIKV infection triggered a strong
      type-I interferon (IFN) response, critical for survival. IFN was mainly expressed
      by neutrophils and hepatocytes. Cell type specific ablation experiments further
      demonstrated that neutrophils play a crucial, unexpected role in CHIKV
      containment. Altogether, our results show that the zebrafish represents a novel
      valuable model to dynamically visualize replication, pathogenesis and host
      responses to a human virus. 

PMID- 24039583
TI  - The JNK pathway is a key mediator of Anopheles gambiae antiplasmodial immunity.
AB  - The innate immune system of Anopheles gambiae mosquitoes limits Plasmodium
      infection through multiple molecular mechanisms. For example, midgut invasion by
      the parasite triggers an epithelial nitration response that promotes activation
      of the complement-like system. We found that suppression of the JNK pathway, by
      silencing either Hep, JNK, Jun or Fos expression, greatly enhanced Plasmodium
      infection; while overactivating this cascade, by silencing the suppressor
      Puckered, had the opposite effect. The JNK pathway limits infection via two
      coordinated responses. It induces the expression of two enzymes (HPx2 and NOX5)
      that potentiate midgut epithelial nitration in response to Plasmodium infection
      and regulates expression of two key hemocyte-derived immune effectors (TEP1 and
      FBN9). Furthermore, the An. gambiae L3-5 strain that has been genetically
      selected to be refractory (R) to Plasmodium infection exhibits constitutive
      overexpression of genes from the JNK pathway, as well as midgut and hemocyte
      effector genes. Silencing experiments confirmed that this cascade mediates, to a
      large extent, the drastic parasite elimination phenotype characteristic of this
      mosquito strain. In sum, these studies revealed the JNK pathway as a key
      regulator of the ability of An. gambiae mosquitoes to limit Plasmodium infection
      and identified several effector genes mediating these responses. 

PMID- 24039584
TI  - The CLIP-domain serine protease homolog SPCLIP1 regulates complement recruitment
      to microbial surfaces in the malaria mosquito Anopheles gambiae.
AB  - The complement C3-like protein TEP1 of the mosquito Anopheles gambiae is required
      for defense against malaria parasites and bacteria. Two forms of TEP1 are present
      in the mosquito hemolymph, the full-length TEP1-F and the proteolytically
      processed TEP1(cut) that is part of a complex including the leucine-rich repeat
      proteins LRIM1 and APL1C. Here we show that the non-catalytic serine protease
      SPCLIP1 is a key regulator of the complement-like pathway. SPCLIP1 is required
      for accumulation of TEP1 on microbial surfaces, a reaction that leads to lysis of
      malaria parasites or triggers activation of a cascade culminating with
      melanization of malaria parasites and bacteria. We also demonstrate that the two
      forms of TEP1 have distinct roles in the complement-like pathway and provide the
      first evidence for a complement convertase-like cascade in insects analogous to
      that in vertebrates. Our findings establish that core principles of complement
      activation are conserved throughout the evolution of animals.

PMID- 24039585
TI  - Calcineurin plays key roles in the dimorphic transition and virulence of the
      human pathogenic zygomycete Mucor circinelloides.
AB  - Many pathogenic fungi are dimorphic and switch between yeast and filamentous
      states. This switch alters host-microbe interactions and is critical for
      pathogenicity. However, in zygomycetes, whether dimorphism contributes to
      virulence is a central unanswered question. The pathogenic zygomycete Mucor
      circinelloides exhibits hyphal growth in aerobic conditions but switches to multi
      budded yeast growth under anaerobic/high CO2 conditions. We found that in the
      presence of the calcineurin inhibitor FK506, Mucor exhibits exclusively multi
      budded yeast growth. We also found that M. circinelloides encodes three
      calcineurin catalytic A subunits (CnaA, CnaB, and CnaC) and one calcineurin
      regulatory B subunit (CnbR). Mutations in the latch region of CnbR and in the
      FKBP12-FK506 binding domain of CnaA result in hyphal growth of Mucor in the
      presence of FK506. Disruption of the cnbR gene encoding the sole calcineurin B
      subunit necessary for calcineurin activity yielded mutants locked in permanent
      yeast phase growth. These findings reveal that the calcineurin pathway plays key
      roles in the dimorphic transition from yeast to hyphae. The cnbR yeast-locked
      mutants are less virulent than the wild-type strain in a heterologous host
      system, providing evidence that hyphae or the yeast-hyphal transition are linked
      to virulence. Protein kinase A activity (PKA) is elevated during yeast growth
      under anaerobic conditions, in the presence of FK506, or in the yeast-locked cnbR
      mutants, suggesting a novel connection between PKA and calcineurin. cnaA mutants
      lacking the CnaA catalytic subunit are hypersensitive to calcineurin inhibitors,
      display a hyphal polarity defect, and produce a mixture of yeast and hyphae in
      aerobic culture. The cnaA mutants also produce spores that are larger than wild
      type, and spore size is correlated with virulence potential. Our results
      demonstrate that the calcineurin pathway orchestrates the yeast-hyphal and spore
      size dimorphic transitions that contribute to virulence of this common zygomycete
      fungal pathogen.

PMID- 24039590
TI  - Genetic and anatomical basis of the barrier separating wakefulness and anesthetic
      induced unresponsiveness.
AB  - A robust, bistable switch regulates the fluctuations between wakefulness and
      natural sleep as well as those between wakefulness and anesthetic-induced
      unresponsiveness. We previously provided experimental evidence for the existence
      of a behavioral barrier to transitions between these states of arousal, which we
      call neural inertia. Here we show that neural inertia is controlled by processes
      that contribute to sleep homeostasis and requires four genes involved in
      electrical excitability: Sh, sss, na and unc79. Although loss of function
      mutations in these genes can increase or decrease sensitivity to anesthesia
      induction, surprisingly, they all collapse neural inertia. These effects are
      genetically selective: neural inertia is not perturbed by loss-of-function
      mutations in all genes required for the sleep/wake cycle. These effects are also
      anatomically selective: sss acts in different neurons to influence arousal
      promoting and arousal-suppressing processes underlying neural inertia. Supporting
      the idea that anesthesia and sleep share some, but not all, genetic and
      anatomical arousal-regulating pathways, we demonstrate that increasing
      homeostatic sleep drive widens the neural inertial barrier. We propose that
      processes selectively contributing to sleep homeostasis and neural inertia may be
      impaired in pathophysiological conditions such as coma and persistent vegetative
      states. 

PMID- 24039591
TI  - Ablating adult neurogenesis in the rat has no effect on spatial processing:
      evidence from a novel pharmacogenetic model.
AB  - The function of adult neurogenesis in the rodent brain remains unclear. Ablation
      of adult born neurons has yielded conflicting results about emotional and
      cognitive impairments. One hypothesis is that adult neurogenesis in the
      hippocampus enables spatial pattern separation, allowing animals to distinguish
      between similar stimuli. We investigated whether spatial pattern separation and
      other putative hippocampal functions of adult neurogenesis were altered in a
      novel genetic model of neurogenesis ablation in the rat. In rats engineered to
      express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic
      protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats
      showed no significant difference from controls in spatial pattern separation on
      the radial maze, spatial learning in the water maze, contextual or cued fear
      conditioning. Meta-analysis of all published studies found no significant effects
      for ablation of adult neurogenesis on spatial memory, cue conditioning or
      ethological measures of anxiety. An effect on contextual freezing was significant
      at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple
      testing. The meta-analysis revealed remarkably high levels of heterogeneity among
      studies of hippocampal function. The source of this heterogeneity remains unclear
      and poses a challenge for studies of the function of adult neurogenesis.

PMID- 24039592
TI  - Environmental stresses disrupt telomere length homeostasis.
AB  - Telomeres protect the chromosome ends from degradation and play crucial roles in
      cellular aging and disease. Recent studies have additionally found a correlation
      between psychological stress, telomere length, and health outcome in humans.
      However, studies have not yet explored the causal relationship between stress and
      telomere length, or the molecular mechanisms underlying that relationship. Using
      yeast as a model organism, we show that stresses may have very different
      outcomes: alcohol and acetic acid elongate telomeres, whereas caffeine and high
      temperatures shorten telomeres. Additional treatments, such as oxidative stress,
      show no effect. By combining genome-wide expression measurements with a
      systematic genetic screen, we identify the Rap1/Rif1 pathway as the central
      mediator of the telomeric response to environmental signals. These results
      demonstrate that telomere length can be manipulated, and that a carefully
      regulated homeostasis may become markedly deregulated in opposing directions in
      response to different environmental cues. 

PMID- 24039593
TI  - Genome-wide mutation avalanches induced in diploid yeast cells by a base analog
      or an APOBEC deaminase.
AB  - Genetic information should be accurately transmitted from cell to cell;
      conversely, the adaptation in evolution and disease is fueled by mutations. In
      the case of cancer development, multiple genetic changes happen in somatic
      diploid cells. Most classic studies of the molecular mechanisms of mutagenesis
      have been performed in haploids. We demonstrate that the parameters of the
      mutation process are different in diploid cell populations. The genomes of drug
      resistant mutants induced in yeast diploids by base analog 6-hydroxylaminopurine
      (HAP) or AID/APOBEC cytosine deaminase PmCDA1 from lamprey carried a stunning
      load of thousands of unselected mutations. Haploid mutants contained almost an
      order of magnitude fewer mutations. To explain this, we propose that the
      distribution of induced mutation rates in the cell population is uneven. The
      mutants in diploids with coincidental mutations in the two copies of the reporter
      gene arise from a fraction of cells that are transiently hypersensitive to the
      mutagenic action of a given mutagen. The progeny of such cells were never
      recovered in haploids due to the lethality caused by the inactivation of single
      copy essential genes in cells with too many induced mutations. In diploid cells,
      the progeny of hypersensitive cells survived, but their genomes were saturated by
      heterozygous mutations. The reason for the hypermutability of cells could be
      transient faults of the mutation prevention pathways, like sanitization of
      nucleotide pools for HAP or an elevated expression of the PmCDA1 gene or the
      temporary inability of the destruction of the deaminase. The hypothesis on spikes
      of mutability may explain the sudden acquisition of multiple mutational changes
      during evolution and carcinogenesis. 

PMID- 24039595
TI  - Genome analysis of a transmissible lineage of pseudomonas aeruginosa reveals
      pathoadaptive mutations and distinct evolutionary paths of hypermutators.
AB  - Genome sequencing of bacterial pathogens has advanced our understanding of their
      evolution, epidemiology, and response to antibiotic therapy. However, we still
      have only a limited knowledge of the molecular changes in in vivo evolving
      bacterial populations in relation to long-term, chronic infections. For example,
      it remains unclear what genes are mutated to facilitate the establishment of long
      term existence in the human host environment, and in which way acquisition of a
      hypermutator phenotype with enhanced rates of spontaneous mutations influences
      the evolutionary trajectory of the pathogen. Here we perform a retrospective
      study of the DK2 clone type of P. aeruginosa isolated from Danish patients
      suffering from cystic fibrosis (CF), and analyze the genomes of 55 bacterial
      isolates collected from 21 infected individuals over 38 years. Our phylogenetic
      analysis of 8,530 mutations in the DK2 genomes shows that the ancestral DK2 clone
      type spread among CF patients through several independent transmission events.
      Subsequent to transmission, sub-lineages evolved independently for years in
      separate hosts, creating a unique possibility to study parallel evolution and
      identification of genes targeted by mutations to optimize pathogen fitness
      (pathoadaptive mutations). These genes were related to antibiotic resistance, the
      cell envelope, or regulatory functions, and we find that the prevalence of
      pathoadaptive mutations correlates with evolutionary success of co-evolving sub
      lineages. The long-term co-existence of both normal and hypermutator populations
      enabled comparative investigations of the mutation dynamics in homopolymeric
      sequences in which hypermutators are particularly prone to mutations. We find a
      positive exponential correlation between the length of the homopolymer and its
      likelihood to acquire mutations and identify two homopolymer-containing genes
      preferentially mutated in hypermutators. This homopolymer facilitated
      differential mutagenesis provides a novel genome-wide perspective on the
      different evolutionary trajectories of hypermutators, which may help explain
      their emergence in CF infections. 

PMID- 24039594
TI  - VAPB/ALS8 MSP ligands regulate striated muscle energy metabolism critical for
      adult survival in caenorhabditis elegans.
AB  - Mutations in VAPB/ALS8 are associated with amyotrophic lateral sclerosis (ALS)
      and spinal muscular atrophy (SMA), two motor neuron diseases that often include
      alterations in energy metabolism. We have shown that C. elegans and Drosophila
      neurons secrete a cleavage product of VAPB, the N-terminal major sperm protein
      domain (vMSP). Secreted vMSPs signal through Roundabout and Lar-like receptors
      expressed on striated muscle. The muscle signaling pathway localizes mitochondria
      to myofilaments, alters their fission/fusion balance, and promotes energy
      production. Here, we show that neuronal loss of the C. elegans VAPB homolog
      triggers metabolic alterations that appear to compensate for muscle mitochondrial
      dysfunction. When vMSP levels drop, cytoskeletal or mitochondrial abnormalities
      in muscle induce elevated DAF-16, the Forkhead Box O (FoxO) homolog,
      transcription factor activity. DAF-16 promotes muscle triacylglycerol
      accumulation, increases ATP levels in adults, and extends lifespan, despite
      reduced muscle mitochondria electron transport chain activity. Finally, Vapb
      knock-out mice exhibit abnormal muscular triacylglycerol levels and FoxO target
      gene transcriptional responses to fasting and refeeding. Our data indicate that
      impaired vMSP signaling to striated muscle alters FoxO activity, which affects
      energy metabolism. Abnormalities in energy metabolism of ALS patients may thus
      constitute a compensatory mechanism counterbalancing skeletal muscle
      mitochondrial dysfunction. 

PMID- 24039596
TI  - Type I-E CRISPR-cas systems discriminate target from non-target DNA through base
      pairing-independent PAM recognition.
AB  - Discriminating self and non-self is a universal requirement of immune systems.
      Adaptive immune systems in prokaryotes are centered around repetitive loci called
      CRISPRs (clustered regularly interspaced short palindromic repeat), into which
      invader DNA fragments are incorporated. CRISPR transcripts are processed into
      small RNAs that guide CRISPR-associated (Cas) proteins to invading nucleic acids
      by complementary base pairing. However, to avoid autoimmunity it is essential
      that these RNA-guides exclusively target invading DNA and not complementary DNA
      sequences (i.e., self-sequences) located in the host's own CRISPR locus. Previous
      work on the Type III-A CRISPR system from Staphylococcus epidermidis has
      demonstrated that a portion of the CRISPR RNA-guide sequence is involved in self
      versus non-self discrimination. This self-avoidance mechanism relies on sensing
      base pairing between the RNA-guide and sequences flanking the target DNA. To
      determine if the RNA-guide participates in self versus non-self discrimination in
      the Type I-E system from Escherichia coli we altered base pairing potential
      between the RNA-guide and the flanks of DNA targets. Here we demonstrate that
      Type I-E systems discriminate self from non-self through a base pairing
      independent mechanism that strictly relies on the recognition of four
      unchangeable PAM sequences. In addition, this work reveals that the first base
      pair between the guide RNA and the PAM nucleotide immediately flanking the target
      sequence can be disrupted without affecting the interference phenotype.
      Remarkably, this indicates that base pairing at this position is not involved in
      foreign DNA recognition. Results in this paper reveal that the Type I-E mechanism
      of avoiding self sequences and preventing autoimmunity is fundamentally different
      from that employed by Type III-A systems. We propose the exclusive targeting of
      PAM-flanked sequences to be termed a target versus non-target discrimination
      mechanism. 

PMID- 24039597
TI  - Bi-modal distribution of the second messenger c-di-GMP controls cell fate and
      asymmetry during the caulobacter cell cycle.
AB  - Many bacteria mediate important life-style decisions by varying levels of the
      second messenger c-di-GMP. Behavioral transitions result from the coordination of
      complex cellular processes such as motility, surface adherence or the production
      of virulence factors and toxins. While the regulatory mechanisms responsible for
      these processes have been elucidated in some cases, the global pleiotropic
      effects of c-di-GMP are poorly understood, primarily because c-di-GMP networks
      are inherently complex in most bacteria. Moreover, the quantitative relationships
      between cellular c-di-GMP levels and c-di-GMP dependent phenotypes are largely
      unknown. Here, we dissect the c-di-GMP network of Caulobacter crescentus to
      establish a global and quantitative view of c-di-GMP dependent processes in this
      organism. A genetic approach that gradually reduced the number of diguanylate
      cyclases identified novel c-di-GMP dependent cellular processes and unraveled c
      di-GMP as an essential component of C. crescentus cell polarity and its bimodal
      life cycle. By varying cellular c-di-GMP concentrations, we determined dose
      response curves for individual c-di-GMP-dependent processes. Relating these
      values to c-di-GMP levels modeled for single cells progressing through the cell
      cycle sets a quantitative frame for the successive activation of c-di-GMP
      dependent processes during the C. crescentus life cycle. By reconstructing a
      simplified c-di-GMP network in a strain devoid of c-di-GMP we defined the minimal
      requirements for the oscillation of c-di-GMP levels during the C. crescentus cell
      cycle. Finally, we show that although all c-di-GMP dependent cellular processes
      were qualitatively restored by artificially adjusting c-di-GMP levels with a
      heterologous diguanylate cyclase, much higher levels of the second messenger are
      required under these conditions as compared to the contribution of homologous c
      di-GMP metabolizing enzymes. These experiments suggest that a common c-di-GMP
      pool cannot fully explain spatiotemporal regulation by c-di-GMP in C. crescentus
      and that individual enzymes preferentially regulate specific phenotypes during
      the cell cycle. 

PMID- 24039598
TI  - An enhancer element harboring variants associated with systemic lupus
      erythematosus engages the TNFAIP3 promoter to influence A20 expression.
AB  - Functional characterization of causal variants present on risk haplotypes
      identified through genome-wide association studies (GWAS) is a primary objective
      of human genetics. In this report, we evaluate the function of a pair of tandem
      polymorphic dinucleotides, 42 kb downstream of the promoter of TNFAIP3,
      (rs148314165, rs200820567, collectively referred to as TT>A) recently nominated
      as causal variants responsible for genetic association of systemic lupus
      erythematosus (SLE) with tumor necrosis factor alpha inducible protein 3
      (TNFAIP3). TNFAIP3 encodes the ubiquitin-editing enzyme, A20, a key negative
      regulator of NF-kappaB signaling. A20 expression is reduced in subjects carrying
      the TT>A risk alleles; however, the underlying functional mechanism by which this
      occurs is unclear. We used a combination of electrophoretic mobility shift assays
      (EMSA), mass spectrometry (MS), reporter assays, chromatin immunoprecipitation
      PCR (ChIP-PCR) and chromosome conformation capture (3C) EBV transformed
      lymphoblastoid cell lines (LCL) from individuals carrying risk and non-risk
      TNFAIP3 haplotypes to characterize the effect of TT>A on A20 expression. Our
      results demonstrate that the TT>A variants reside in an enhancer element that
      binds NF-kappaB and SATB1 enabling physical interaction of the enhancer with the
      TNFAIP3 promoter through long-range DNA looping. Impaired binding of NF-kappaB to
      the TT>A risk alleles or knockdown of SATB1 expression by shRNA, inhibits the
      looping interaction resulting in reduced A20 expression. Together, these data
      reveal a novel mechanism of TNFAIP3 transcriptional regulation and establish the
      functional basis by which the TT>A risk variants attenuate A20 expression through
      inefficient delivery of NF-kappaB to the TNFAIP3 promoter. These results provide
      critical functional evidence supporting a direct causal role for TT>A in the
      genetic predisposition to SLE. 

PMID- 24039599
TI  - Stochastic loss of silencing of the imprinted Ndn/NDN allele, in a mouse model
      and humans with prader-willi syndrome, has functional consequences.
AB  - Genomic imprinting is a process that causes genes to be expressed from one allele
      only according to parental origin, the other allele being silent. Diseases can
      arise when the normally active alleles are not expressed. In this context, low
      level of expression of the normally silent alleles has been considered as genetic
      noise although such expression has never been further studied. Prader-Willi
      Syndrome (PWS) is a neurodevelopmental disease involving imprinted genes,
      including NDN, which are only expressed from the paternally inherited allele,
      with the maternally inherited allele silent. We present the first in-depth study
      of the low expression of a normally silent imprinted allele, in pathological
      context. Using a variety of qualitative and quantitative approaches and comparing
      wild-type, heterozygous and homozygous mice deleted for Ndn, we show that, in
      absence of the paternal Ndn allele, the maternal Ndn allele is expressed at an
      extremely low level with a high degree of non-genetic heterogeneity. The level of
      this expression is sex-dependent and shows transgenerational epigenetic
      inheritance. In about 50% of mutant mice, this expression reduces birth lethality
      and severity of the breathing deficiency, correlated with a reduction in the loss
      of serotonergic neurons. In wild-type brains, the maternal Ndn allele is never
      expressed. However, using several mouse models, we reveal a competition between
      non-imprinted Ndn promoters which results in monoallelic (paternal or maternal)
      Ndn expression, suggesting that Ndn allelic exclusion occurs in the absence of
      imprinting regulation. Importantly, specific expression of the maternal NDN
      allele is also detected in post-mortem brain samples of PWS individuals. Our data
      reveal an unexpected epigenetic flexibility of PWS imprinted genes that could be
      exploited to reactivate the functional but dormant maternal alleles in PWS.
      Overall our results reveal high non-genetic heterogeneity between genetically
      identical individuals that might underlie the variability of the phenotype. 

PMID- 24039601
TI  - Functional dissection of regulatory models using gene expression data of deletion
      mutants.
AB  - Genome-wide gene expression profiles accumulate at an alarming rate, how to
      integrate these expression profiles generated by different laboratories to
      reverse engineer the cellular regulatory network has been a major challenge. To
      automatically infer gene regulatory pathways from genome-wide mRNA expression
      profiles before and after genetic perturbations, we introduced a new Bayesian
      network algorithm: Deletion Mutant Bayesian Network (DM_BN). We applied DM_BN to
      the expression profiles of 544 yeast single or double deletion mutants of
      transcription factors, chromatin remodeling machinery components, protein kinases
      and phosphatases in S. cerevisiae. The network inferred by this method identified
      causal regulatory and non-causal concurrent interactions among these regulators
      (genetically perturbed genes) that are strongly supported by the experimental
      evidence, and generated many new testable hypotheses. Compared to networks
      reconstructed by routine similarity measures or by alternative Bayesian network
      algorithms, the network inferred by DM_BN excels in both precision and recall. To
      facilitate its application in other systems, we packaged the algorithm into a
      user-friendly analysis tool that can be downloaded at
      http://www.picb.ac.cn/hanlab/DM_BN.html. 

PMID- 24039600
TI  - Divergent transcriptional regulatory logic at the intersection of tissue growth
      and developmental patterning.
AB  - The Yorkie/Yap transcriptional coactivator is a well-known regulator of cellular
      proliferation in both invertebrates and mammals. As a coactivator, Yorkie (Yki)
      lacks a DNA binding domain and must partner with sequence-specific DNA binding
      proteins in the nucleus to regulate gene expression; in Drosophila, the
      developmental regulators Scalloped (Sd) and Homothorax (Hth) are two such
      partners. To determine the range of target genes regulated by these three
      transcription factors, we performed genome-wide chromatin immunoprecipitation
      experiments for each factor in both the wing and eye-antenna imaginal discs.
      Strong, tissue-specific binding patterns are observed for Sd and Hth, while Yki
      binding is remarkably similar across both tissues. Binding events common to the
      eye and wing are also present for Sd and Hth; these are associated with genes
      regulating cell proliferation and "housekeeping" functions, and account for the
      majority of Yki binding. In contrast, tissue-specific binding events for Sd and
      Hth significantly overlap enhancers that are active in the given tissue, are
      enriched in Sd and Hth DNA binding sites, respectively, and are associated with
      genes that are consistent with each factor's previously established tissue
      specific functions. Tissue-specific binding events are also significantly
      associated with Polycomb targeted chromatin domains. To provide mechanistic
      insights into tissue-specific regulation, we identify and characterize eye and
      wing enhancers of the Yki-targeted bantam microRNA gene and demonstrate that they
      are dependent on direct binding by Hth and Sd, respectively. Overall these
      results suggest that both Sd and Hth use distinct strategies - one shared between
      tissues and associated with Yki, the other tissue-specific, generally Yki
      independent and associated with developmental patterning - to regulate distinct
      gene sets during development. 

PMID- 24039602
TI  - The arabidopsis IDD14, IDD15, and IDD16 cooperatively regulate lateral organ
      morphogenesis and gravitropism by promoting auxin biosynthesis and transport.
AB  - The plant hormone auxin plays a critical role in regulating various aspects of
      plant growth and development, and the spatial accumulation of auxin within
      organs, which is primarily attributable to local auxin biosynthesis and polar
      transport, is largely responsible for lateral organ morphogenesis and the
      establishment of plant architecture. Here, we show that three Arabidopsis
      INDETERMINATE DOMAIN (IDD) transcription factors, IDD14, IDD15, and IDD16,
      cooperatively regulate auxin biosynthesis and transport and thus aerial organ
      morphogenesis and gravitropic responses. Gain-of-function of each IDD gene in
      Arabidopsis results in small and transversally down-curled leaves, whereas loss
      of-function of these IDD genes causes pleiotropic phenotypes in aerial organs and
      defects in gravitropic responses, including altered leaf shape, flower
      development, fertility, and plant architecture. Further analyses indicate that
      these IDD genes regulate spatial auxin accumulation by directly targeting YUCCA5
      (YUC5), TRYPTOPHAN AMINOTRANSFERASE of ARABIDOPSIS1 (TAA1), and PIN-FORMED1
      (PIN1) to promote auxin biosynthesis and transport. Moreover, mutation or ectopic
      expression of YUC suppresses the organ morphogenic phenotype and partially
      restores the gravitropic responses in gain- or loss-of-function idd mutants,
      respectively. Taken together, our results reveal that a subfamily of IDD
      transcription factors plays a critical role in the regulation of spatial auxin
      accumulation, thereby controlling organ morphogenesis and gravitropic responses
      in plants. 

PMID- 24039603
TI  - Plasticity regulators modulate specific root traits in discrete nitrogen
      environments.
AB  - Plant development is remarkably plastic but how precisely can the plant customize
      its form to specific environments? When the plant adjusts its development to
      different environments, related traits can change in a coordinated fashion, such
      that two traits co-vary across many genotypes. Alternatively, traits can vary
      independently, such that a change in one trait has little predictive value for
      the change in a second trait. To characterize such "tunability" in developmental
      plasticity, we carried out a detailed phenotypic characterization of complex root
      traits among 96 accessions of the model Arabidopsis thaliana in two nitrogen
      environments. The results revealed a surprising level of independence in the
      control of traits to environment - a highly tunable form of plasticity. We mapped
      genetic architecture of plasticity using genome-wide association studies and
      further used gene expression analysis to narrow down gene candidates in mapped
      regions. Mutants in genes implicated by association and expression analysis
      showed precise defects in the predicted traits in the predicted environment,
      corroborating the independent control of plasticity traits. The overall results
      suggest that there is a pool of genetic variability in plants that controls
      traits in specific environments, with opportunity to tune crop plants to a given
      environment. 

PMID- 24039604
TI  - Convergent transcription induces dynamic DNA methylation at disiRNA loci.
AB  - Cytosine methylation of DNA is an important epigenetic gene silencing mechanism
      in plants, fungi, and animals. In the filamentous fungus Neurospora crassa,
      nearly all known DNA methylations occur in transposon relics and repetitive
      sequences, and DNA methylation does not depend on the canonical RNAi pathway.
      disiRNAs are Dicer-independent small non-coding RNAs that arise from gene-rich
      part of the Neurospora genome. Here we describe a new type of DNA methylation
      that is associated with the disiRNA loci. Unlike the known DNA methylation in
      Neurospora, disiRNA loci DNA methylation (DLDM) is highly dynamic and is
      regulated by an on/off mechanism. Some disiRNA production appears to rely on pol
      II directed transcription. Importantly, DLDM is triggered by convergent
      transcription and enriched in promoter regions. Together, our results establish a
      new mechanism that triggers DNA methylation. 

PMID- 24039605
TI  - Dynamics of DNA methylation in recent human and great ape evolution.
AB  - DNA methylation is an epigenetic modification involved in regulatory processes
      such as cell differentiation during development, X-chromosome inactivation,
      genomic imprinting and susceptibility to complex disease. However, the dynamics
      of DNA methylation changes between humans and their closest relatives are still
      poorly understood. We performed a comparative analysis of CpG methylation
      patterns between 9 humans and 23 primate samples including all species of great
      apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450
      bead arrays. Our analysis identified ~800 genes with significantly altered
      methylation patterns among the great apes, including ~170 genes with a
      methylation pattern unique to human. Some of these are known to be involved in
      developmental and neurological features, suggesting that epigenetic changes have
      been frequent during recent human and primate evolution. We identified a
      significant positive relationship between the rate of coding variation and
      alterations of methylation at the promoter level, indicative of co-occurrence
      between evolution of protein sequence and gene regulation. In contrast, and
      supporting the idea that many phenotypic differences between humans and great
      apes are not due to amino acid differences, our analysis also identified 184
      genes that are perfectly conserved at protein level between human and chimpanzee,
      yet show significant epigenetic differences between these two species. We
      conclude that epigenetic alterations are an important force during primate
      evolution and have been under-explored in evolutionary comparative genomics. 

PMID- 24039606
TI  - The Uve1 endonuclease is regulated by the white collar complex to protect
      cryptococcus neoformans from UV damage.
AB  - The pathogenic fungus Cryptococcus neoformans uses the Bwc1-Bwc2 photoreceptor
      complex to regulate mating in response to light, virulence and ultraviolet
      radiation tolerance. How the complex controls these functions is unclear. Here,
      we identify and characterize a gene in Cryptococcus, UVE1, whose mutation leads
      to a UV hypersensitive phenotype. The homologous gene in fission yeast
      Schizosaccharomyces pombe encodes an apurinic/apyrimidinic endonuclease acting in
      the UVDE-dependent excision repair (UVER) pathway. C. neoformans UVE1 complements
      a S. pombe uvde knockout strain. UVE1 is photoregulated in a Bwc1-dependent
      manner in Cryptococcus, and in Neurospora crassa and Phycomyces blakesleeanus
      that are species that represent two other major lineages in the fungi.
      Overexpression of UVE1 in bwc1 mutants rescues their UV sensitivity phenotype and
      gel mobility shift experiments show binding of Bwc2 to the UVE1 promoter,
      indicating that UVE1 is a direct downstream target for the Bwc1-Bwc2 complex.
      Uve1-GFP fusions localize to the mitochondria. Repair of UV-induced damage to the
      mitochondria is delayed in the uve1 mutant strain. Thus, in C. neoformans UVE1 is
      a key gene regulated in response to light that is responsible for tolerance to UV
      stress for protection of the mitochondrial genome. 

PMID- 24039607
TI  - Transmission of Hypervirulence traits via sexual reproduction within and between
      lineages of the human fungal pathogen cryptococcus gattii.
AB  - Since 1999 a lineage of the pathogen Cryptococcus gattii has been infecting
      humans and other animals in Canada and the Pacific Northwest of the USA. It is
      now the largest outbreak of a life-threatening fungal infection in a healthy
      population in recorded history. The high virulence of outbreak strains is closely
      linked to the ability of the pathogen to undergo rapid mitochondrial
      tubularisation and proliferation following engulfment by host phagocytes. Most
      outbreaks spread by geographic expansion across suitable niches, but it is known
      that genetic re-assortment and hybridisation can also lead to rapid range and
      host expansion. In the context of C. gattii, however, the likelihood of virulence
      traits associated with the outbreak lineages spreading to other lineages via
      genetic exchange is currently unknown. Here we address this question by
      conducting outgroup crosses between distantly related C. gattii lineages (VGII
      and VGIII) and ingroup crosses between isolates from the same molecular type
      (VGII). Systematic phenotypic characterisation shows that virulence traits are
      transmitted to outgroups infrequently, but readily inherited during ingroup
      crosses. In addition, we observed higher levels of biparental (as opposed to
      uniparental) mitochondrial inheritance during VGII ingroup sexual mating in this
      species and provide evidence for mitochondrial recombination following mating.
      Taken together, our data suggest that hypervirulence can spread among the C.
      gattii lineages VGII and VGIII, potentially creating novel hypervirulent
      genotypes, and that current models of uniparental mitochondrial inheritance in
      the Cryptococcus genus may not be universal. 

PMID- 24039608
TI  - Cell interactions and patterned intercalations shape and link epithelial tubes in
      C. elegans.
AB  - Many animal organs are composed largely or entirely of polarized epithelial
      tubes, and the formation of complex organ systems, such as the digestive or
      vascular systems, requires that separate tubes link with a common polarity. The
      Caenorhabditis elegans digestive tract consists primarily of three interconnected
      tubes-the pharynx, valve, and intestine-and provides a simple model for
      understanding the cellular and molecular mechanisms used to form and connect
      epithelial tubes. Here, we use live imaging and 3D reconstructions of developing
      cells to examine tube formation. The three tubes develop from a pharynx/valve
      primordium and a separate intestine primordium. Cells in the pharynx/valve
      primordium polarize and become wedge-shaped, transforming the primordium into a
      cylindrical cyst centered on the future lumenal axis. For continuity of the
      digestive tract, valve cells must have the same, radial axis of apicobasal
      polarity as adjacent intestinal cells. We show that intestinal cells contribute
      to valve cell polarity by restricting the distribution of a polarizing cue,
      laminin. After developing apicobasal polarity, many pharyngeal and valve cells
      appear to explore their neighborhoods through lateral, actin-rich lamellipodia.
      For a subset of cells, these lamellipodia precede more extensive intercalations
      that create the valve. Formation of the valve tube begins when two valve cells
      become embedded at the left-right boundary of the intestinal primordium. Other
      valve cells organize symmetrically around these two cells, and wrap partially or
      completely around the orthogonal, lumenal axis, thus extruding a small valve tube
      from the larger cyst. We show that the transcription factors DIE-1 and EGL
      43/EVI1 regulate cell intercalations and cell fates during valve formation, and
      that the Notch pathway is required to establish the proper boundary between the
      pharyngeal and valve tubes. 

PMID- 24039609
TI  - An alteration in ELMOD3, an Arl2 GTPase-activating protein, is associated with
      hearing impairment in humans.
AB  - Exome sequencing coupled with homozygosity mapping was used to identify a
      transition mutation (c.794T>C; p.Leu265Ser) in ELMOD3 at the DFNB88 locus that is
      associated with nonsyndromic deafness in a large Pakistani family, PKDF468. The
      affected individuals of this family exhibited pre-lingual, severe-to-profound
      degrees of mixed hearing loss. ELMOD3 belongs to the engulfment and cell motility
      (ELMO) family, which consists of six paralogs in mammals. Several members of the
      ELMO family have been shown to regulate a subset of GTPases within the Ras
      superfamily. However, ELMOD3 is a largely uncharacterized protein that has no
      previously known biochemical activities. We found that in rodents, within the
      sensory epithelia of the inner ear, ELMOD3 appears most pronounced in the
      stereocilia of cochlear hair cells. Fluorescently tagged ELMOD3 co-localized with
      the actin cytoskeleton in MDCK cells and actin-based microvilli of LLC-PK1-CL4
      epithelial cells. The p.Leu265Ser mutation in the ELMO domain impaired each of
      these activities. Super-resolution imaging revealed instances of close
      association of ELMOD3 with actin at the plasma membrane of MDCK cells.
      Furthermore, recombinant human GST-ELMOD3 exhibited GTPase activating protein
      (GAP) activity against the Arl2 GTPase, which was completely abolished by the
      p.Leu265Ser mutation. Collectively, our data provide the first insights into the
      expression and biochemical properties of ELMOD3 and highlight its functional
      links to sound perception and actin cytoskeleton. 

PMID- 24039610
TI  - Cell-type specific features of circular RNA expression.
AB  - Thousands of loci in the human and mouse genomes give rise to circular RNA
      transcripts; at many of these loci, the predominant RNA isoform is a circle.
      Using an improved computational approach for circular RNA identification, we
      found widespread circular RNA expression in Drosophila melanogaster and estimate
      that in humans, circular RNA may account for 1% as many molecules as poly(A) RNA.
      Analysis of data from the ENCODE consortium revealed that the repertoire of genes
      expressing circular RNA, the ratio of circular to linear transcripts for each
      gene, and even the pattern of splice isoforms of circular RNAs from each gene
      were cell-type specific. These results suggest that biogenesis of circular RNA is
      an integral, conserved, and regulated feature of the gene expression program. 

PMID- 24039612
TI  - Take off, landing, and fly anesthesia.

PMID- 24039611
TI  - Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila
      MJD/SCA3 model.
AB  - There are no effective therapeutics that antagonize or reverse the protein
      misfolding events underpinning polyglutamine (PolyQ) disorders, including
      Spinocerebellar Ataxia Type-3 (SCA3). Here, we augment the proteostasis network
      of Drosophila SCA3 models with Hsp104, a powerful protein disaggregase from
      yeast, which is bafflingly absent from metazoa. Hsp104 suppressed eye
      degeneration caused by a C-terminal ataxin-3 (MJD) fragment containing the
      pathogenic expanded PolyQ tract, but unexpectedly enhanced aggregation and
      toxicity of full-length pathogenic MJD. Hsp104 suppressed toxicity of MJD
      variants lacking a portion of the N-terminal deubiquitylase domain and full
      length MJD variants unable to engage polyubiquitin, indicating that MJD-ubiquitin
      interactions hinder protective Hsp104 modalities. Importantly, in staging
      experiments, Hsp104 suppressed toxicity of a C-terminal MJD fragment when
      expressed after the onset of PolyQ-induced degeneration, whereas Hsp70 was
      ineffective. Thus, we establish the first disaggregase or chaperone treatment
      administered after the onset of pathogenic protein-induced degeneration that
      mitigates disease progression. 

PMID- 24039613
TI  - Targeted preoperative autologous blood donation in total knee arthroplasty
      reduces the need for postoperative transfusion.
AB  - BACKGROUND: Preoperative donation of autologous blood has been widely used to
      minimize the potential risk of allogeneic transfusions in total knee
      arthroplasty. A previous study from our center revealed that preoperative
      autologous donation reduces the allogeneic blood exposure for anemic patients but
      has no effect for non-anemic patients. QUESTIONS/PURPOSES: The current study
      investigates the impact of a targeted blood donation protocol on overall
      transfusion rates and the incidence of allogeneic blood transfusions. METHODS:
      Prospectively, 372 patients undergoing 425 unilateral primary knee replacements
      were preoperatively screened by the Blood Preservation Center between 2009 and
      2012. Anemic patients with a hemoglobin level less than 13.5 g/dL were advised to
      donate blood, while non-anemic patients did not donate. RESULTS: Non-anemic
      patients who did not donate blood required allogeneic blood transfusions in 5.9%
      of the patients. The overall rate of allogeneic transfusion was significantly
      lower for anemic patients who donated autologous blood (group A, 9%) than those
      who did not donate (group B, 33%; p < 0.001). Donating autologous blood did
      increase the overall transfusion rate of anemic patients to 0.84 per patient in
      group A compared to 0.41 per patient in group B (p < 0.001). CONCLUSION: This
      investigation confirms that abandoning preoperative autologous blood donation for
      non-anemic patients does not increase allogeneic blood transfusion rates but
      significantly lowers overall transfusion rates.

PMID- 24039614
TI  - Imaging Metal-on-Metal Hip Replacements: the Norwich Experience.
AB  - BACKGROUND: Adverse reaction to metal debris is a relatively recently described
      and often a silent complication of metal-on-metal (MOM) total hip replacements
      (THR). The Norfolk & Norwich University Hospital has been performing metal
      artefact reduction (MARS) MRI for 8 years in a variety of different types of MOM
      THR. QUESTIONS/PURPOSES: The aims of this review are to describe the experience
      of using MARS MRI in Norwich and to compare our experience with that published by
      other groups. METHODS: A MEDLINE keyword search was performed for studies
      including MRI in MOM THR. Relevant publications were reviewed and compared with
      published data from the Norfolk & Norwich University Hospital. The similarities
      and differences between these data were compared and possible explanations for
      these discussed. RESULTS: MARS MRI appears to be the most useful tool for
      diagnosing, staging and monitoring adverse reactions to metal debris (ARMD).
      There appears to be no clinically useful association between clinical and
      serological markers of disease and the severity of MR findings. Although severe
      early ARMD is associated with significant morbidity, mild disease is often stable
      for years. If patients with normal initial MR examinations develop ARMD, this
      usually occurs 7 years. A 1-year interval between MRI examinations is reasonable
      in asymptomatic patients. CONCLUSIONS: There is a general international consensus
      that ARMD is prevalent in symptomatic and asymptomatic patients with MOM THR and
      that while appearances vary with the type of prosthesis, there are characteristic
      features that make MARS MRI essential for diagnosis, staging and surveillance of
      the disease.

PMID- 24039616
TI  - Proposed minimum reporting standards for chemical analysis Chemical Analysis
      Working Group (CAWG) Metabolomics Standards Initiative (MSI).
AB  - There is a general consensus that supports the need for standardized reporting of
      metadata or information describing large-scale metabolomics and other functional
      genomics data sets. Reporting of standard metadata provides a biological and
      empirical context for the data, facilitates experimental replication, and enables
      the re-interrogation and comparison of data by others. Accordingly, the
      Metabolomics Standards Initiative is building a general consensus concerning the
      minimum reporting standards for metabolomics experiments of which the Chemical
      Analysis Working Group (CAWG) is a member of this community effort. This article
      proposes the minimum reporting standards related to the chemical analysis aspects
      of metabolomics experiments including: sample preparation, experimental analysis,
      quality control, metabolite identification, and data pre-processing. These
      minimum standards currently focus mostly upon mass spectrometry and nuclear
      magnetic resonance spectroscopy due to the popularity of these techniques in
      metabolomics. However, additional input concerning other techniques is welcomed
      and can be provided via the CAWG on-line discussion forum at http://msi
      workgroups.sourceforge.net/ or http://Msi-workgroups
      feedback@lists.sourceforge.net. Further, community input related to this document
      can also be provided via this electronic forum.

PMID- 24039615
TI  - Dissecting virus-plant interactions through proteomics approaches.
AB  - Plant viruses exploit cellular factors, including host proteins, membranes and
      metabolites, for their replication in infected cells and to establish systemic
      infections. Besides traditional genetic, molecular, cellular and biochemical
      methods studying plant-virus interactions, both global and specialized proteomics
      methods are emerging as useful approaches for the identification of all the host
      proteins that play roles in virus infections. The various proteomics approaches
      include measuring differential protein expression in virus infected versus
      noninfected cells, analysis of viral and host protein components in the viral
      replicase or other virus-induced complexes, as well as proteome-wide screens to
      identify host protein - viral protein interactions using protein arrays or yeast
      two-hybrid assays. In this review, we will discuss the progress made in plant
      virology using various proteomics methods, and highlight the functions of some of
      the identified host proteins during viral infections. Since global proteomics
      approaches do not usually identify the molecular mechanism of the identified host
      factors during viral infections, additional experiments using genetics,
      biochemistry, cell biology and other approaches should also be performed to
      characterize the functions of host factors. Overall, the ever-improving
      proteomics approaches promise further understanding of plant-virus interactions
      that will likely result in new strategies for viral disease control in plants.

PMID- 24039617
TI  - Metabolomic approach to evaluating adriamycin pharmacodynamics and resistance in
      breast cancer cells.
AB  - Continuous exposure of breast cancer cells to adriamycin induces high expression
      of P-gp and multiple drug resistance. However, the biochemical process and the
      underlying mechanisms for the gradually induced resistance are not clear. To
      explore the underlying mechanism and evaluate the anti-tumor effect and
      resistance of adriamycin, the drug-sensitive MCF-7S and the drug-resistant MCF
      7Adr breast cancer cells were used and treated with adriamycin, and the
      intracellular metabolites were profiled using gas chromatography mass
      spectrometry. Principal components analysis of the data revealed that the two
      cell lines showed distinctly different metabolic responses to adriamycin.
      Adriamycin exposure significantly altered metabolic pattern of MCF-7S cells,
      which gradually became similar to the pattern of MCF-7Adr, indicating that
      metabolic shifts were involved in adriamycin resistance. Many intracellular
      metabolites involved in various metabolic pathways were significantly modulated
      by adriamycin treatment in the drug-sensitive MCF-7S cells, but were much less
      affected in the drug-resistant MCF-7Adr cells. Adriamycin treatment markedly
      depressed the biosynthesis of proteins, purines, pyrimidines and glutathione, and
      glycolysis, while it enhanced glycerol metabolism of MCF-7S cells. The elevated
      glycerol metabolism and down-regulated glutathione biosynthesis suggested an
      increased reactive oxygen species (ROS) generation and a weakened ability to
      balance ROS, respectively. Further studies revealed that adriamycin increased ROS
      and up-regulated P-gp in MCF-7S cells, which could be reversed by N
      acetylcysteine treatment. It is suggested that adriamycin resistance is involved
      in slowed metabolism and aggravated oxidative stress. Assessment of cellular
      metabolomics and metabolic markers may be used to evaluate anti-tumor effects and
      to screen for candidate anti-tumor agents.

PMID- 24039618
TI  - Comparative analysis of volatile metabolomics signals from melanoma and benign
      skin: a pilot study.
AB  - The analysis of volatile organic compounds (VOC) as biomarkers of cancer is both
      promising and challenging. In this pilot study, we used an untargeted approach to
      compare volatile metabolomic signatures of melanoma and matched control non
      neoplastic skin from the same patient. VOC from fresh (non-fixed) biopsied tissue
      were collected using the headspace solid phase micro extraction method (HS SPME)
      and analyzed by gas chromatography and mass spectrometry (GCMS). We applied the
      XCMS analysis platform and MetaboAnalyst software to reveal many differentially
      expressed metabolic features. Our analysis revealed increased levels of lauric
      acid (C12:0) and palmitic acid (C16:0) in melanoma. The identity of these
      compounds was confirmed by comparison with chemical standards. Increased levels
      of these fatty acids are likely to be a consequence of up-regulated de novo lipid
      synthesis, a known characteristic of cancer. Increased oxidative stress is likely
      to cause an additional increase in lauric acid. Implementation of this study
      design on larger number of cases will be necessary for the future metabolomics
      biomarker discovery applications.

PMID- 24039619
TI  - Stearoyl-CoA desaturase enzyme 1 inhibition reduces glucose utilization for de
      novo fatty acid synthesis and cell proliferation in 3T3-L1 adipocytes.
AB  - Stearoyl-CoA desaturase enzyme 1 (SCD1) is a lipogenic enzyme that is upregulated
      in obesity, insulin resistance, and cancer. Since glucose is a substrate for both
      de novo fatty acid synthesis and deoxyribose synthesis, we hypothesized that SCD1
      affects these multiple synthetic pathways through changes in glucose utilization.
      This study determined glucose utilization for fatty acid synthesis and cell
      proliferation in 3T3-L1 preadipocytes during SCD1 inhibition. The effects of SCD1
      on cellular metabolism as mediated by its monounstaurated fatty acid products
      (palmitoleate and oleate) were also observed. 3T3-L1 preadipocytes underwent
      differentiation induction in conjunction with one of the following treatments for
      4 days: (A) no treatment, (B) SCD1 inhibitor CGX0290, (C) CGX0290 + palmitoleate,
      or (D) CGX0290 + oleate. All cells received medium with 50 % [U13C]-glucose.
      Cells were harvested on day 7 for studies of fatty acid metabolism, tricarboxylic
      acid (TCA) cycle activities, and deoxyribose synthesis. CGX0290 decreased fatty
      acid desaturation, glucose utilization for fatty acid synthesis (acetyl-CoA
      enrichment), and de novo synthesis. CGX0290 treatment also led to decreased cell
      density through increased cell death. Further analysis showed that deoxyribose
      new synthesis and oxidative pentose phosphate pathway activity were unchanged,
      while non-oxidative transketolase pathway activity was stimulated. Palmitoleate
      and oleate supplementation each partially ameliorated the effects of CGX0290. In
      3T3-L1 cells, SCD1 promotes glucose utilization for fatty acid synthesis. In cell
      proliferation, SCD1 may promote cell survival, but does not impact the oxidative
      pathway of deoxyribose production. These effects may be mediated through the
      production of palmitoleate and oleate.

PMID- 24039620
TI  - A behavioral economic supplement to brief motivational interventions for college
      drinking.
AB  - Basic behavioral and neurobiological research has demonstrated that deficiencies
      in naturally occurring substance-free rewards are both a cause and a consequence
      of substance abuse that are due in part to the systematic discounting of delayed
      substance-free rewards. Existing brief motivational interventions (BMIs) for
      alcohol abuse do not target this mechanism of change. The goal of this
      uncontrolled pilot study was to evaluate a behavioral economic Substance-Free
      Activity Session (SFAS) to traditional alcohol BMIs. Participants were 13 college
      freshmen who reported two or more heavy drinking episodes (>5/4 drinks in an
      occasion for men/ women) in the past month. All participants completed a baseline
      assessment and a BMI that addressed alcohol use. In addition, participants
      received the SFAS, a 50-min individual session that attempts to increase
      engagement in constructive alternatives to drinking by enhancing the salience of
      delayed rewards (academic and career success) and the patterns of behavior
      (academic and extracurricular engagement) leading to these outcomes. At the 1
      month follow-up assessment, participants reported significant reductions in heavy
      drinking, and moderate to large effect size reductions in weekly drinking and
      peak blood alcohol levels. The results of this pilot study provide preliminary
      support for the efficacy of this behavioral economic intervention session as a
      supplement to traditional alcohol BMIs.

PMID- 24039621
TI  - Below replacement fertility preferences in Shanghai.
AB  - China has joined the group of low-fertility countries; it has a TFR somewhere in
      the range of 1.4 to 1.6. Much speculation about China's future fertility depends
      on whether individual's fertility intentions and preferences are much higher than
      the state's fertility goals. If so, then a relaxation of family planning
      restrictions could lead to a substantial fertility increase. We directly ask a
      probability sample of Shanghai registered residents and migrants whether a policy
      relaxation would lead them to have additional children. Our results show that
      small families (one or two children) are intended in this urban setting. If
      family planning policy were relaxed, a relatively small fraction (fewer than 14%)
      reports that they would revise their intentions upward. Even this modest increase
      (as much as 10%) is suspect because factors that can deflate fertility relative
      to intentions are likely more powerful than the inflationary ones (in Shanghai).
      These empirical findings help ground speculations on the future of fertility in
      the hypothetical absence of policy constraints.

PMID- 24039622
TI  - Semiparametric Mixed Effect Model with Application to the Longitudinal Knee
      Osteoarthritis (OAK) Data.
AB  - Motivated by the study of the longitudinal development and progression of knee
      osteoarthritis (OA) over a 15-year period, this study developed non-parametric
      mixed-effect models for ordinal outcomes. A stochastic mixed-effect model was
      used to evaluate the similarity of trajectories associated with increasing
      disease severity of OA in both knees. Then, a non-parametric mixed-effects model,
      based on cubic B-splnes, was developed to characterize the unknown nonlinear
      trend of logits as a function of time1-order. A Markov Transition Model was
      developed to characterize the transitions among multi-states of knee OA. This
      newly developed approach allows more flexible functional dependence of the
      ordinal outcome, levels of increasing knee OA severity, on the covariates.

PMID- 24039623
TI  - Obesity and Cardiac Function - The Role of Caloric Excess and its Reversal.
AB  - Obesity is recognized as an independent and increasingly prevalent risk factor
      for cardiovascular morbidity and mortality. This stems in part from the
      contribution of obesity towards insulin resistance and diabetes, which associate
      with premature atherosclerosis, enhanced thrombogenicity and activation of
      systemic inflammatory programs with resultant cardiovascular dysfunction. This
      review will focus on the more direct mechanisms underpinning obesity-associated
      cardiac pathophysiology including the metabolic consequences of lipid
      accumulation in the myocardium and the consequences of direct systemic effects of
      lipid toxicity. Furthermore, there is growing recognition that metabolic
      intermediates, which may be perturbed with caloric excess, may play an important
      role in intracellular signal transduction and on the post-translational control
      of metabolic functioning within the heart. As strategies to reverse obesity
      appear to have ameliorative cardiac effects, surgical and therapeutic approaches
      to facilitate weight reduction this will also be discussed.

PMID- 24039624
TI  - Personalized medicine: challenges and opportunities for translational
      bioinformatics.
AB  - Personalized medicine can be defined broadly as a model of healthcare that is
      predictive, personalized, preventive and participatory. Two US President's
      Council of Advisors on Science and Technology reports illustrate challenges in
      personalized medicine (in a 2008 report) and in use of health information
      technology (in a 2010 report). Translational bioinformatics is a field that can
      help address these challenges and is defined by the American Medical Informatics
      Association as "the development of storage, analytic and interpretive methods to
      optimize the transformation of increasing voluminous biomedical data into
      proactive, predictive, preventative and participatory health." This article
      discusses barriers to implementing genomics applications and current progress
      toward overcoming barriers, describes lessons learned from early experiences of
      institutions engaged in personalized medicine and provides example areas for
      translational bioinformatics research inquiry.

PMID- 24039625
TI  - Controlling assembly of helical polypeptides via PEGylation strategies.
AB  - Recent studies in our laboratories have demonstrated that a helical polypeptide
      (17H6), equipped with a histidine tag and a helical alanine-rich, glutamic-acid
      containing domain, exhibits pH-responsive assembly behavior useful in the
      production of polymorphological nanostructures. In this study, the histidine tag
      in these polypeptides was replaced by polyethylene glycol (PEG) with different
      molecular masses (5 kDa, or 10 kDa), and the self-association behavior of 17H6
      and the PEGylated conjugates was characterized via dynamic light scattering
      (DLS), small angle neutron scattering (SANS), and cryogenic transmission electron
      microscopy (cryo-TEM). DLS experiments illustrated that the polypeptide and its
      PEG-conjugates undergo reversible assembly under acidic conditions, suggesting
      that the aggregation state of the polypeptide and the conjugates is controlled by
      the charged state of the glutamic acid residues. Nanoscale aggregates were
      detected at polypeptide/conjugate concentrations as low as 20 MUM (~0.3-0.5 mg ml
      1) at physiological and ambient temperatures. Scattering and microscopy results
      showed that the size, the aggregation number, and the morphology of the
      aggregates can be tuned by the size and the nature of the hydrophilic tag. This
      tunable nature of the morphology of the aggregates, along with their low critical
      aggregation concentration, suggests that PEG-alanine-rich polypeptide conjugates
      may be useful as drug delivery vehicles in which the alanine-rich block serves as
      a drug attachment domain.

PMID- 24039626
TI  - HIV+ and HIV- youth living in group homes in South Africa need more psychosocial
      support.
AB  - Orphans and vulnerable youth who live in group homes are at risk of poor mental
      health and sexual and drug-using behaviors that increase the risk of HIV
      transmission. This study explores factors related to this risk among youth living
      in group homes ("children's homes") for orphans and vulnerable children in South
      Africa, a country afflicted by high levels of parental loss due to HIV. The study
      explores 1) knowledge and attitudes about HIV, 2) social support, 3)
      communication with group home caregivers, and 4) the relevance of an existing
      evidence-based HIV prevention and mental health promotion program to situations
      where sexual and drug risk behaviors can occur. In-depth qualitative individual
      interviews were conducted with 20 youth (age 10 to 16 years) residing in two
      children's homes in Durban, South Africa. Content analysis focused on critical
      themes related to coping and prevention of risk activities. Respondents exhibited
      inconsistent and incomplete knowledge of HIV transmission and prevention. They
      displayed positive attitudes toward people living with HIV, but reported
      experiencing or witnessing HIV-related stigma. Participants witnessed substance
      use and romantic/sexual relationships among their peers; few admitted to their
      own involvement. While relationships with childcare workers were central to their
      lives, youth reported communication barriers related to substance use, sex, HIV,
      and personal history (including parental loss, abuse, and other trauma). In
      conclusion, these qualitative data suggest that evidence-based HIV prevention
      programs that bring caregivers and youth together to improve communication, HIV
      knowledge, social support, youth self-esteem, and health care, reduce sexual and
      drug risk behaviors, and strengthen skills related to negotiating situations of
      sexual and substance use possibility could benefit youth and childcare workers in
      children's homes.

PMID- 24039627
TI  - Modeling retinal degenerative diseases with human iPS-derived cells: current
      status and future implications.

PMID- 24039628
TI  - Modulating the tumor immune microenvironment as an ovarian cancer treatment
      strategy.
AB  - After more than 30 years of iterations of surgical debulking plus chemotherapy,
      the need for complementary ovarian cancer treatments has become clear. In the
      ovarian cancer microenvironment, myeloid immunosuppressive leukocytes,
      lymphocytes, fibroblasts and endothelial cells, as well as their secreted
      products, surface molecules and paracrine survival factors, all provide
      opportunities for novel interventions. The potential of targeting
      microenvironmental elements in ovarian cancer patients is underscored by recently
      successful anti-angiogenic therapies. The compartmentalized nature of ovarian
      cancer, its immunogenicity and its accessibility make it an ideal disease for
      targeting non-tumor host cells. This review discusses the 'state-of-the-art' of
      the field, with an emphasis on the potential of modulating the activity of
      abundant microenvironmental immune cells, which govern both angiogenesis and
      immunosuppression.

PMID- 24039629
TI  - Spanking and Child Development: We Know Enough Now To Stop Hitting Our Children.
AB  - Spanking remains a common, if controversial, childrearing practice in the United
      States. In this article, I pair mounting research indicating that spanking is
      both ineffective and harmful with professional and human rights opinions
      disavowing the practice. I conclude that spanking is a form of violence against
      children that should no longer be a part of American childrearing.

PMID- 24039630
TI  - Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for
      Malignant Peritoneal Mesothelioma.
AB  - Malignant peritoneal mesothelioma (MPM) is a rare and aggressive neoplasm that is
      largely resistant to traditional anti-cancer therapies. For years it has been
      considered a terminal condition and once diagnosed, patients generally survived
      less than a year despite aggressive treatment. Although rare, the worldwide
      incidence of MPM continues to rise, in part due to its association with asbestos
      exposure. Patients usually present with non-specific symptoms of abdominal
      distension and pain making the diagnosis challenging. In recent years, aggressive
      cytoreductive surgery with the administration of hyperthermic intraperitoneal
      chemotherapy (HIPEC) has improved survival in patients with MPM treated at
      multiple centers worldwide. This review article briefly highlights the
      presentation, diagnosis, and natural history of MPM. We then explore the
      available treatment options with primary focus on cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy.

PMID- 24039631
TI  - Prevalence of Candida co-infection in patients with pulmonary tuberculosis.
AB  - BACKGROUND: Candida species are emerging as a potentially pathogenic fungus in
      patients with broncho-pulmonary diseases. The synergistic growth promoting
      association of Candida and Mycobacterium tuberculosis has raised increased
      concern for studying the various Candida spp . and its significance in pulmonary
      tuberculosis patients during current years. AIMS: This study was undertaken with
      the objective of discovering the prevalence of co-infection caused by different
      Candida species in patients with pulmonary tuberculosis. METHOD: A total of 75
      patients with pulmonary tuberculosis diagnosed by sputum Ziehl-Neelsen staining
      were included in the study. Candida co-infection was confirmed using the Kahanpaa
      et al. criteria. Candida species were identified using gram stain morphology,
      germ tube formation, morphology on cornmeal agar with Tween-80, sugar
      fermentation tests and HiCrome Candida Agar. RESULTS: Candida co-infection was
      observed in 30 (40%) of patients with pulmonary tuberculosis. Candida albicans
      was the most common isolate observed in 50% of the patients with co-infection,
      followed by C. tropicalis (20%) and C. glabrata (20%). Candida co-infection was
      found in 62.5% of female patients, while it was observed in only 29.4% of the
      male patients (P value 0.0133). Mean +/- SD age of the patients with C. glabrata
      infection was 65.83 +/- 3.19, while the mean +/- SD age of the patients with
      other Candida infections was 43.25 +/- 20.44 (P value 0.0138). CONCLUSION: Many
      patients with pulmonary tuberculosis have co-infection with Candida spp. The
      prevalence of non-albicans Candida species is increasing and may be associated
      with inadequate response to anti-tubercular drugs. C. glabrata infection has a
      strong association with old age.

PMID- 24039632
TI  - Triple falx cerebelli associated with two aberrant venous sinuses in the floor of
      posterior cranial fossa.
AB  - During regular dissection classes, we came across tripled falx cerebelli in a
      male cadaver. The main (middle) falx cerebelli was large and was attached to the
      internal occipital crest. It contained the occipital sinus. There were two
      smaller folds (right and left), one on either side of the falx cerebelli. There
      were two aberrant venous sinuses; each one connecting the ipsilateral sigmoid and
      transverse sinuses with each other. The complex dural-venous variation reported
      here is seldom reported in the literature. Knowledge of such variation is
      important for neurosurgeons and neuroradiologists as these aberrant folds could
      cause haemorrhage during suboccipital approaches or may lead to erroneous
      interpretation during imaging of the posterior cranial fossa. 

PMID- 24039633
TI  - A case report of melioidosis in a diabetic patient in a union territory.
AB  - Melioidosis is an emerging disease in India. Cases have also been reported from
      South East Asia, Australia and Japan. Major risk factors for melioidosis are
      diabetes mellitus, preexisting renal disease and thalassemia. Exposure to
      contaminated soil and water are also significant occupational hazards associated
      with the disease. A patient with diabetes of six years duration on regular
      medication presented with fever, generalised myalgia and headache for a week.
      Blood and bone marrow culture yielded Burkholderia pseudomallei. A Computed
      tomography (CT) study of the thorax also revealed multiple scattered nodules in
      both lungs. The patient was treated with imipenem and doxycycline. His condition
      improved gradually and he was advised oral sulfamethoxazole/trimethoprim and
      doxycycline for a period of three months and has been followed up regularly. 

PMID- 24039634
TI  - Ovarian pregnancy: two case reports.
AB  - Ovarian pregnancy is a rare event occurring in 1-3% of all ectopic pregnancies.
      Increased reporting might be due to the wider use of intra-uterine devices,
      ovulatory drugs and assisted reproductive techniques. Though ovarian pregnancy
      has a distinct pathology, it can be a source of clinical and intraoperative
      diagnostic difficulty. We report two cases of ovarian pregnancy - one primary and
      one secondary - that came to our notice within six months span. Unlike tubal
      ectopic and secondary ovarian pregnancies, patients with primary ovarian
      pregnancy are likely to experience success in future intra-uterine conception and
      negligible risk. 

PMID- 24039635
TI  - Self-reported bowel screening rates in older Australians and the implications for
      public health screening programs.
AB  - BACKGROUND: This paper sought to determine the status of older Australians with
      regard to Bowel Cancer screening practices occurring outside of the National
      Bowel Cancer Screening Program. METHOD: A random sample of N=25,511 urban
      Australians aged 50 to 74 years received a questionnaire via mail asking
      questions relating to bowel screening. N=8,762 (34.3%) returned a completed
      questionnaire. RESULTS: Approximately 33% (N=2863) of respondents indicated they
      had undergone colonoscopy in the preceding five years and 21% (N=1840) had used a
      Faecal Occult Blood Test (FOBT) in the preceding 12 months. Furthermore, 27%
      (N=497) of those who had completed an FOBT had also undergone colonoscopy.
      CONCLUSION: A significant proportion of older Australians might be participating
      in bowel screening practices outside of the national program (NBCSP). Moreover,
      the proportion of individuals reporting use of both FOBT and endoscopic services
      is much higher than the positivity rate of FOBT. Large population FOBT screening
      programs, such as the NBCSP, that do not consider participation in screening
      external to the program may underestimate true population screening rates.

PMID- 24039636
TI  - Interactive CaringTV(r) supporting elderly living at home.
AB  - BACKGROUND: Interactive CaringTV(r) is a Finnish innovation that was developed by
      Laurea University of Applied Sciences in 2006. CaringTV was developed through
      action research during three research projects. The aim of interactive CaringTV
      is to support the health and well-being of elderly people living in their own
      homes. METHOD: The Safe Home project was based on action research, userdriven
      methods, and a case study. User-driven methods were applied in planning,
      implementing and evaluating the programme and eServices e.g. testing and
      evaluating peer support, including eConsultation as the methods for supporting
      clients' coping with life in their own homes. Costeffectiveness and process
      modelling were studied through the case study. RESULTS: The user-driven approach
      and the collected data formed the basis for the interactive programme. The online
      CaringTV programme included content to: support everyday life for the elderly,
      safety, and activities of daily living, support social relationships, participate
      in rehabilitation and physical exercises, manage self-care, and health issues.
      Active participation in the CaringTV programme provided functional ability and
      everyday coping as well as a meaningful activity in everyday life. CONCLUSION:
      CaringTV is an interactive platform to support elderly in their everyday life and
      help them cope at home. User-driven methods enable participants' active
      involvement in planning interactive and online programmes and eServices via
      CaringTV. The ultimate goal of the CaringTV is to support elderly's health,
      wellbeing and interaction. CaringTV empowers elderly people to take
      responsibility for their own health care as part of healthy ageing.

PMID- 24039637
TI  - FLUCTUATING MOTOR FORCES BEND GROWING MICROTUBULES.
AB  - Despite their rigidity, microtubules in living cells bend significantly during
      polymerization resulting in greater curvature than can be explained by thermal
      forces alone. However, the source of the non-thermal forces that bend growing
      microtubules remains obscure. We analyzed the motion of microtubule tips in NIH
      3T3 fibroblasts expressing EGFP-EB1, a fluorescent +TIP protein that specifically
      binds to the growing ends of microtubules. We found that dynein inhibition
      significantly reduced the deviation of the growing tip from its initial
      trajectory. Inhibiting myosin modestly reduced tip fluctuations, while
      simultaneous myosin and dynein inhibition caused no further decrease in
      fluctuations compared to dynein inhibition alone. Our results can be interpreted
      with a model in which dynein linkages play a key role in generating and
      transmitting fluctuating forces that bend growing microtubules.

PMID- 24039638
TI  - Comparative effectiveness of dynamic treatment regimes: an application of the
      parametric g-formula.
AB  - Ideally, randomized trials would be used to compare the long-term effectiveness
      of dynamic treatment regimes on clinically relevant outcomes. However, because
      randomized trials are not always feasible or timely, we often must rely on
      observational data to compare dynamic treatment regimes. An example of a dynamic
      treatment regime is "start combined antiretroviral therapy (cART) within 6 months
      of CD4 cell count first dropping below x cells/mm3 or diagnosis of an AIDS
      defining illness, whichever happens first" where x can take values between 200
      and 500. Recently, Cain et al (2011) used inverse probability (IP) weighting of
      dynamic marginal structural models to find the x that minimizes 5-year mortality
      risk under similar dynamic regimes using observational data. Unlike standard
      methods, IP weighting can appropriately adjust for measured time-varying
      confounders (e.g., CD4 cell count, viral load) that are affected by prior
      treatment. Here we describe an alternative method to IP weighting for comparing
      the effectiveness of dynamic cART regimes: the parametric g-formula. The
      parametric g-formula naturally handles dynamic regimes and, like IP weighting,
      can appropriately adjust for measured time-varying confounders. However,
      estimators based on the parametric g-formula are more efficient than IP weighted
      estimators. This is often at the expense of more parametric assumptions. Here we
      describe how to use the parametric g-formula to estimate risk by the end of a
      user-specified follow-up period under dynamic treatment regimes. We describe an
      application of this method to answer the "when to start" question using data from
      the HIV-CAUSAL Collaboration.

PMID- 24039639
TI  - Nutrition knowledge of low-income parents of obese children.
AB  - Minority and low-income children are overrepresented among obese US children.
      Lack of basic nutrition knowledge among parents may contribute to this disparity.
      The purpose of this study is to measure nutrition knowledge of parents of
      Medicaid-insured obese children using a simple low-literacy tool. Parents,
      recruited from pediatric clinics, demonstrated their nutrition knowledge by
      placing food stickers into cells on a printed grid with food groups displayed in
      columns and three nutrition categories displayed in rows. In general, parents (n
      = 135; 74.8 % black; 79.2 % income of <=$25,000/year) correctly identified food
      groups (median = 90.5 % correct). Nutritional categories were more commonly
      misidentified (median = 67 % correct), with parents mostly believing foods were
      healthier than they were. Multivariable linear regression revealed black race (p
      = 0.02), no college education (p = 0.02) and income of <$15,000 (p = 0.03)
      independently predicted misidentification of nutritional categories. Parents'
      understanding of food's nutritional value is variable. Black race, less
      education, and very low income are associated with poorer nutrition knowledge. 

PMID- 24039640
TI  - Increased RP105-Negative B Cells in IgG4-Related Disease.
AB  - Four patients with IgG4-related disease (IgG4-RD) showed increased percentages of
      RP105-negative B cells in the peripheral blood. Case 1: A 66-year-old man having
      retroperitoneal fibrosis had 18.8% of RP105-negative B cells. Oral prednisolone
      improved the affected lesions and the percentage of RP105-negative B cells
      decreased (3.2%) after the treatment. Case 2: A 53-year-old man with
      retroperitoneal fibrosis had 27.9% of RP105-negative B cells. Case 3: A 38-year
      old man with follicular hyperplasia showed increased percentage of RP105-negative
      B cells (8.3%). Case 4: A 60-year-old man with interstitial nephritis had 27.5%
      of RP105-negative B cells. The treatment decreased the numbers of RP105-negative
      B cells. Increased numbers of RP105-negatvie B cells is possibly associated with
      disease activity of IgG4-RD. Analysis of expression of RP105 on B cells may be
      helpful in evaluation of disease activity of IgG4-RD. 

PMID- 24039641
TI  - A case of erosive polyarthritis in a patient diagnosed with a suspicion of
      atypical mycobacteria.
AB  - In this report, we introduce a case of erosive polyarthritis in a 55-year-old
      female diagnosed with Mycobacterium abscessus pulmonary infection. Her arthritis
      has been worsened after use of DMARDs. The patient demonstrated a significant
      response to the antimicrobial regimen that was administered. We call special
      attention to the possibility of Mycobacterium abscessus being a cause of reactive
      polyarthritis, particularly if symptoms worsened after use of disease-modifying
      antirheumatic drugs (DMARDs), but further studies are necessary for
      clarification. 

PMID- 24039642
TI  - Behavioral health order sets in a hybrid information environment.
AB  - INTRODUCTION: The Centre for Addiction and Mental Health (CAMH) is a 500 bed
      freestanding psychiatric hospital in Canada. We are in the process of preparing
      for an integrated commercial clinical information system, which will have
      computerized physician order entry (CPOE) functionality. METHODS: As a
      preparation for CPOE, we developed inpatient order sets (OSs). Development teams
      from individual clinical programs created and sent their OSs to an OS Working
      Group for initial endorsement, and then to Pharmacy & Therapeutics and Medical
      Advisory committees subsequent approvals. RESULTS: In twelve months we created
      and introduced 22 behavioral health OSs across eight clinical programs in our
      hybrid information system with an excellent adoption rate (>97%) by clinicians.
      DISCUSSION: The development and implementation temporarily contributed to a
      multifactorial flow problem in the emergency department (ED), which was addressed
      by substantially simplifying the General Admission via the ED OS. Also, as the
      OSs were developed and sent for approval the project identified areas where local
      clinical practice can improve. Our electronic-paper hybrid set of clinical
      systems was a major factor impacting the effort.

PMID- 24039643
TI  - Beliefs about health, health risks and health expectations from the perspective
      of people with a psychotic disorder.
AB  - AIM: To examine beliefs about health, health risks and health expectations from
      the perspective of people diagnosed with a psychotic disorder. BACKGROUND: People
      with psychotic disorders have a threefold higher risk of developing physical
      health problems than the general population, and prevention of these problems is
      warranted. Examining patients' health beliefs could help deepen our understanding
      of how to plan successful health interventions with this group. METHODS:
      Qualitative semi-structured interviews were conducted from November 2010 to
      October 2011 with 17 people with psychotic disorders. Data were analyzed using a
      qualitative content analysis. RESULTS: An overall positive picture of health was
      found despite the fact that physical health was found to be hard to verbalize and
      understand. Health was mainly associated with psychological wellbeing, while
      health risks were found to be related to uncertain bodily identity, troublesome
      thoughts and inner voices, and exclusion from society. Interest in learning, and
      visions and goals of health seemed to increase awareness of health risks and
      health expectations, while not worrying could be viewed as a hindrance for health
      expectations. CONCLUSION: There is a lack of expressed awareness of physical
      health risks, but such awareness is fundamental to performing life-style changes
      [14]. Nurses thus have an important task to help patients understand and
      verbalize potential physical health risks, and to find out what motivates them to
      adopt health behaviors.

PMID- 24039644
TI  - The influence of beliefs about health and illness on foot care in ugandan persons
      with diabetic foot ulcers.
AB  - Diabetes mellitus is becoming pandemic, particularly affecting Sub-Saharan
      Africa, and the prevalence of complications is increasing. Diabetic foot
      disorders are a major source of morbidity and disability. Delay in the health
      care process due to patients' beliefs may have deleterious consequences for limb
      and life in persons with diabetic foot ulcers. No previous studies of beliefs
      about health and illness in persons with diabetic foot ulcers living in Africa
      have been found. The aim of the study was to explore beliefs about health and
      illness among Ugandans with diabetic foot ulcers that might affect self-care and
      care seeking behaviour. In an explorative study with consecutive sample semi
      structured interviews were held with 14 Ugandan men and women, aged 40-79, with
      diabetic foot ulcer. Knowledge was limited about causes, management and
      prevention of diabetic foot ulcers. Foot ulcers were often detected as painful
      sores, perceived to heal or improve, and led to stress and social isolation due
      to smell and reduced mobility. Most lacked awareness of the importance of
      complete daily foot care and seldom practised self-care. Health was described as
      absence of disease and pain. Many feared future health and related it to contact
      with nurses in the professional sector from whom they sought information, blood
      tests and wound dressings and desired better organised diabetes clinics offering
      health education and more opening hours. Many have an underutilised potential for
      self-care and need education urgently, delivered in well-organised diabetes
      clinics working to raise awareness of the threat and prevent foot ulcers. 

PMID- 24039645
TI  - Factors Involved in Iranian Women Heads of Household's Health Promotion
      Activities: A Grounded Theory Study.
AB  - We aimed to explore and describe the factors involved in Iranian women heads of
      household's health promotion activities. Grounded theory was used as the method.
      Sixteen women heads of household were recruited. Data were generated by semi
      structured interviews. Our findings indicated that remainder of resources (money,
      time and energy) alongside perceived severity of health risk were two main
      factors whereas women's personal and socio-economic characteristics were two
      contextual factors involved in these women's health promotion activities. To help
      these women improve their health status, we recommended that the government, non
      governmental organizations and health care professionals provide them with
      required resources and increase their knowledge by holding training sessions. 

PMID- 24039666
TI  - Imbalance between HAT and HDAC activities in the PBMCs of patients with
      ankylosing spondylitis or rheumatoid arthritis and influence of HDAC inhibitors
      on TNF alpha production.
AB  - OBJECTIVE: Acetylation or deacetylation of histone proteins may modulate cytokine
      gene transcription such as TNF alpha (TNF). We evaluated the balance between
      histone deacetytlase (HDAC) and histone acetyltransferase (HAT) in patients with
      rheumatoid arthritis (RA) or ankylosing spondylitis (AS) compared to healthy
      controls (HC) and determined the influence of HDAC inhibitors (trichostatin A 
      TSA- or Sirtinol -Sirt-) on these enzymatic activities and on the PBMC production
      of TNF. METHODS: 52 patients with RA, 21 with AS and 38 HC were evaluated. HAT
      and HDAC activities were measured on nuclear extracts from PBMC using
      colorimetric assays. Enzymatic activities were determined prior to and after ex
      vivo treatment of PBMC by TSA or Sirt. TNF levels were evaluated in PBMC culture
      supernatants in the absence or presence of TSA or Sirt. RESULTS: HAT and HDAC
      activities were significantly reduced in AS, while these activities reached
      similar levels in RA and HC. Ex vivo treatment of PBMC by HDACi tended to
      decrease HDAC expression in HC, but Sirt significantly reduced HAT in RA. TNF
      production by PBMC was significantly down-regulated by Sirt in HC and AS
      patients. CONCLUSION: HAT and HDAC were disturbed in AS while no major changes
      were found in RA. HDACi may modulate HDAC and HAT PBMC expression, especially
      Sirt in RA. Sirtinol was able to down regulate TNF production by PBMC in HC and
      AS. An imbalance between HAT and HDAC activities might provide the rationale for
      the development of HDACi in the therapeutic approach to inflammatory rheumatic
      diseases.

PMID- 24039667
TI  - Large-scale distribution and activity of prokaryotes in deep-sea surface
      sediments of the Mediterranean Sea and the adjacent Atlantic Ocean.
AB  - The deep-sea represents a substantial portion of the biosphere and has a major
      influence on carbon cycling and global biogeochemistry. Benthic deep-sea
      prokaryotes have crucial roles in this ecosystem, with their recycling of organic
      matter from the photic zone. Despite this, little is known about the large-scale
      distribution of prokaryotes in the surface deep-sea sediments. To assess the
      influence of environmental and trophic variables on the large-scale distribution
      of prokaryotes, we investigated the prokaryotic assemblage composition (Bacteria
      to Archaea and Euryarchaeota to Crenarchaeota ratio) and activity in the surface
      deep-sea sediments of the Mediterranean Sea and the adjacent North Atlantic
      Ocean. Prokaryotic abundance and biomass did not vary significantly across the
      Mediterranean Sea; however, there were depth-related trends in all areas. The
      abundance of prokaryotes was positively correlated with the sedimentary
      concentration of protein, an indicator of the quality and bioavailability of
      organic matter. Moving eastwards, the Bacteria contribution to the total
      prokaryotes decreased, which appears to be linked to the more oligotrophic
      conditions of the Eastern Mediterranean basins. Despite the increased importance
      of Archaea, the contributions of Crenarchaeota Marine Group I to the total pool
      was relatively constant across the investigated stations, with the exception of
      Matapan-Vavilov Deep, in which Euryarchaeota Marine Group II dominated. Overall,
      our data suggest that deeper areas of the Mediterranean Sea share more similar
      communities with each other than with shallower sites. Freshness and quality of
      sedimentary organic matter were identified through Generalized Additive Model
      analysis as the major factors for describing the variation in the prokaryotic
      community structure and activity in the surface deep-sea sediments. Longitude was
      also important in explaining the observed variability, which suggests that the
      overlying water masses might have a critical role in shaping the benthic
      communities. 

PMID- 24039691
TI  - Characterization and comparison of 2 distinct epidemic community-associated
      methicillin-resistant Staphylococcus aureus clones of ST59 lineage.
AB  - Sequence type (ST) 59 is an epidemic lineage of community-associated (CA)
      methicillin-resistant Staphylococcus aureus (MRSA) isolates. Taiwanese CA-MRSA
      isolates belong to ST59 and can be grouped into 2 distinct clones, a virulent
      Taiwan clone and a commensal Asian-Pacific clone. The Taiwan clone carries the
      Panton-Valentine leukocidin (PVL) genes and the staphylococcal chromosomal
      cassette mec (SCCmec) VT, and is frequently isolated from patients with severe
      disease. The Asian-Pacific clone is PVL-negative, carries SCCmec IV, and a
      frequent colonizer of healthy children. Isolates of both clones were
      characterized by their ability to adhere to respiratory A549 cells, cytotoxicity
      to human neutrophils, and nasal colonization of a murine and murine sepsis
      models. Genome variation was determined by polymerase chain reaction of selected
      virulence factors and by multi-strain whole genome microarray. Additionally, the
      expression of selected factors was compared between the 2 clones. The Taiwan
      clone showed a much higher cytotoxicity to the human neutrophils and caused more
      severe septic infections with a high mortality rate in the murine model. The
      clones were indistinguishable in their adhesion to A549 cells and persistence of
      murine nasal colonization. The microarray data revealed that the Taiwan clone had
      lost the o3-prophage that integrates into the beta-hemolysin gene and includes
      staphylokinase- and enterotoxin P-encoding genes, but had retained the genes for
      human immune evasion, scn and chps. Production of the virulence factors did not
      differ significantly in the 2 clonal groups, although more alpha-toxin was
      expressed in Taiwan clone isolates from pneumonia patients. In conclusion, the
      Taiwan CA-MRSA clone was distinguished by enhanced virulence in both humans and
      an animal infection model. The evolutionary acquisition of PVL, the higher
      expression of alpha-toxin, and possibly the loss of a large portion of the beta
      hemolysin-converting prophage likely contribute to its higher pathogenic
      potential than the Asian-Pacific clone. 

PMID- 24039692
TI  - Cdk5 inhibitory peptide (CIP) inhibits Cdk5/p25 activity induced by high glucose
      in pancreatic beta cells and recovers insulin secretion from p25 damage.
AB  - Cdk5/p25 hyperactivity has been demonstrated to lead to neuron apoptosis and
      degenerations. Chronic exposure to high glucose (HG) results in hyperactivity of
      Cdk5 and reduced insulin secretion. Here, we set out to determine whether
      abnormal upregulation of Cdk5/p25 activity may be induced in a pancreatic beta
      cell line, Min6 cells. We first confirmed that p25 were induced in overexpressed
      p35 cells treated with HG and increased time course dependence. Next, we showed
      that no p25 was detected under short time HG stimulation (4-12 hrs), however was
      detectable in the long exposure in HG cells (24 hrs and 48 hrs). Cdk5 activity in
      the above cells was much higher than low glucose treated cells and resulted in
      more than 50% inhibition of insulin secretion. We confirmed these results by
      overexpression of p25 in Min6 cells. As in cortical neurons, CIP, a small
      peptide, inhibited Cdk5/p25 activity and restored insulin secretion. The same
      results were detected in co-infection of dominant negative Cdk5 (DNCdk5) with
      p25. CIP also reduced beta cells apoptosis induced by Cdk5/p25. These studies
      indicate that Cdk5/p25 hyperactivation deregulates insulin secretion and induces
      cell death in pancreatic beta cells and suggests that CIP may serve as a
      therapeutic agent for type 2 diabetes. 

PMID- 24039668
TI  - Induction of the unfolded protein response drives enhanced metabolism and
      chemoresistance in glioma cells.
AB  - The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-based
      cytoprotective mechanism acting to prevent pathologies accompanying protein
      aggregation. It is frequently active in tumors, but relatively unstudied in
      gliomas. We hypothesized that UPR stress effects on glioma cells might protect
      tumors from additional exogenous stress (ie, chemotherapeutics), postulating that
      protection was concurrent with altered tumor cell metabolism. Using human brain
      tumor cell lines, xenograft tumors, human samples and gene expression databases,
      we determined molecular features of glioma cell UPR induction/activation, and
      here report a detailed analysis of UPR transcriptional/translational/metabolic
      responses. Immunohistochemistry, Western and Northern blots identified elevated
      levels of UPR transcription factors and downstream ER chaperone targets in
      gliomas. Microarray profiling revealed distinct regulation of stress responses
      between xenograft tumors and parent cell lines, with gene ontology and network
      analyses linking gene expression to cell survival and metabolic processes. Human
      glioma samples were examined for levels of the ER chaperone GRP94 by
      immunohistochemistry and for other UPR components by Western blotting. Gene and
      protein expression data from patient gliomas correlated poor patient prognoses
      with increased expression of ER chaperones, UPR target genes, and metabolic
      enzymes (glycolysis and lipogenesis). NMR-based metabolomic studies revealed
      increased metabolic outputs in glucose uptake with elevated glycolytic activity
      as well as increased phospholipid turnover. Elevated levels of amino acids,
      antioxidants, and cholesterol were also evident upon UPR stress; in particular,
      recurrent tumors had overall higher lipid outputs and elevated specific UPR arms.
      Clonogenicity studies following temozolomide treatment of stressed or unstressed
      cells demonstrated UPR-induced chemoresistance. Our data characterize the UPR in
      glioma cells and human tumors, and link the UPR to chemoresistance possibly via
      enhanced metabolism. Given the role of the UPR in the balance between cell
      survival and apoptosis, targeting the UPR and/or controlling metabolic activity
      may prove beneficial for malignant glioma therapeutics. 

PMID- 24039693
TI  - Promising Aedes aegypti repellent chemotypes identified through integrated QSAR,
      virtual screening, synthesis, and bioassay.
AB  - Molecular field topology analysis, scaffold hopping, and molecular docking were
      used as complementary computational tools for the design of repellents for Aedes
      aegypti, the insect vector for yellow fever, chikungunya, and dengue fever. A
      large number of analogues were evaluated by virtual screening with Glide
      molecular docking software. This produced several dozen hits that were either
      synthesized or procured from commercial sources. Analysis of these compounds by a
      repellent bioassay resulted in a few highly active chemicals (in terms of minimum
      effective dosage) as viable candidates for further hit-to-lead and lead
      optimization effort. 

PMID- 24039694
TI  - Gray matter is targeted in first-attack multiple sclerosis.
AB  - The cause of multiple sclerosis (MS), its driving pathogenesis at the earliest
      stages, and what factors allow the first clinical attack to manifest remain
      unknown. Some imaging studies suggest gray rather than white matter may be
      involved early, and some postulate this may be predictive of developing MS. Other
      imaging studies are in conflict. To determine if there was objective molecular
      evidence of gray matter involvement in early MS we used high-resolution mass
      spectrometry to identify proteins in the cerebrospinal fluid (CSF) of first
      attack MS patients (two independent groups) compared to established relapsing
      remitting (RR) MS and controls. We found that the CSF proteins in first-attack
      patients were differentially enriched for gray matter components (axon, neuron,
      synapse). Myelin components did not distinguish these groups. The results support
      that gray matter dysfunction is involved early in MS, and also may be integral
      for the initial clinical presentation. 

PMID- 24039696
TI  - Quid pro quo: a mechanism for fair collaboration in networked systems.
AB  - Collaboration may be understood as the execution of coordinated tasks (in the
      most general sense) by groups of users, who cooperate for achieving a common
      goal. Collaboration is a fundamental assumption and requirement for the correct
      operation of many communication systems. The main challenge when creating
      collaborative systems in a decentralized manner is dealing with the fact that
      users may behave in selfish ways, trying to obtain the benefits of the tasks but
      without participating in their execution. In this context, Game Theory has been
      instrumental to model collaborative systems and the task allocation problem, and
      to design mechanisms for optimal allocation of tasks. In this paper, we revise
      the classical assumptions of these models and propose a new approach to this
      problem. First, we establish a system model based on heterogenous nodes (users,
      players), and propose a basic distributed mechanism so that, when a new task
      appears, it is assigned to the most suitable node. The classical technique for
      compensating a node that executes a task is the use of payments (which in most
      networks are hard or impossible to implement). Instead, we propose a distributed
      mechanism for the optimal allocation of tasks without payments. We prove this
      mechanism to be robust evenevent in the presence of independent selfish or
      rationally limited players. Additionally, our model is based on very weak
      assumptions, which makes the proposed mechanisms susceptible to be implemented in
      networked systems (e.g., the Internet). 

PMID- 24039695
TI  - Alcohol and drug use disorders among patients with myocardial infarction:
      associations with disparities in care and mortality.
AB  - BACKGROUND: Because alcohol and drug use disorders (SUDs) can influence quality
      of care, we compared patients with and without SUDs on frequency of
      catheterization, revascularization, and in-hospital mortality after acute
      myocardial infarction (AMI). METHODS: This study employed hospital discharge data
      identifying all adult AMI admissions (ICD-9-CM code 410) between April 1996 and
      December 2001. Patients were classified as having an SUD if they had alcohol
      and/or drug (not nicotine) abuse or dependence using a validated ICD-9-CM coding
      definition. Catheterization and revascularization data were obtained by linkage
      with a clinically-detailed cardiac registry. Analyses (controlling for
      comorbidities and disease severity) compared patients with and without SUDs for
      post-MI catheterization, revascularization, and in-hospital mortality. RESULTS:
      Of 7,876 AMI unique patient admissions, 2.6% had an SUD. In adjusted analyses
      mortality was significantly higher among those with an SUD (odds ratio (OR) 2.02;
      95%CI: 1.10-3.69), while there was a trend toward lower catheterization rates
      among those with an SUD (OR 0.75; 95%CI: 0.55-1.01). Among the subset of AMI
      admissions who underwent catheterization, the adjusted hazard ratio for one-year
      revascularization was 0.85 (95%CI: 0.65-1.11) with an SUD compared to without.
      CONCLUSIONS: Alcohol and drug use disorders are associated with significantly
      higher in-hospital mortality following AMI in adults of all ages, and may also be
      associated with decreased access to catheterization and revascularization. This
      higher mortality in the face of poorer access to procedures suggests that these
      individuals may be under-treated following AMI. Targeted efforts are required to
      explore the interplay of patient and provider factors that underlie this finding.

PMID- 24039697
TI  - Effects of pre-encoding stress on brain correlates associated with the long-term
      memory for emotional scenes.
AB  - Recent animal and human research indicates that stress around the time of
      encoding enhances long-term memory for emotionally arousing events but neural
      evidence remains unclear. In the present study we used the ERP old/new effect to
      investigate brain dynamics underlying the long-term effects of acute pre-encoding
      stress on memory for emotional and neutral scenes. Participants were exposed
      either to the Socially Evaluated Cold Pressure Test (SECPT) or a warm water
      control procedure before viewing 30 unpleasant, 30 neutral and 30 pleasant
      pictures. Two weeks after encoding, recognition memory was tested using 90 old
      and 90 new pictures. Emotional pictures were better recognized than neutral
      pictures in both groups and related to an enhanced centro-parietal ERP old/new
      difference (400-800 ms) during recognition, which suggests better recollection.
      Most interestingly, pre-encoding stress exposure specifically increased the ERP
      old/new-effect for emotional (unpleasant) pictures, but not for neutral pictures.
      These enhanced ERP/old new differences for emotional (unpleasant) scenes were
      particularly pronounced for those participants who reported high levels of stress
      during the SECPT. The results suggest that acute pre-encoding stress specifically
      strengthens brain signals of emotional memories, substantiating a facilitating
      role of stress on memory for emotional scenes. 

PMID- 24039698
TI  - Oleic acid may be the key contributor in the BAMLET-induced erythrocyte hemolysis
      and tumoricidal action.
AB  - A chance discovery of the tumoricidal action of a human milk fraction led to the
      characterization of the active component as oleic acid complex of the alpha
      lactalbumin, which was given the acronym HAMLET. We report in this study that the
      oleic acid complex of bovine alpha-lactalbumin (BAMLET) is hemolytic to human
      erythrocytes as well as to those derived from some other mammals. Indirect
      immunofluorescence analysis suggested binding of BAMLET to erythrocytes prior to
      induction of hemolysis. Free OA was hemolytic albeit at higher concentrations,
      while sodium oleate caused hemolysis at far lower concentrations. Amiloride and
      BaCl2 offered protection against BAMLET-induced hemolysis suggesting the
      involvement of a cation leak channel in the process. BAMLET coupled to CNBr
      activated Sepharose was not only hemolytic but also tumoricidal to Jurkat and MCF
      7 cells in culture. The Sepharose-linked preparation was however not toxic to non
      cancerous peritoneal macrophages and primary adipocytes. The tumoricidal action
      was studied using the MTT-assay while apoptosis induction measured by the annexin
      V-propidium iodide assay. Repeated incubation of the immobilized BAMLET with
      erythrocytes depleted oleic acid and decreased the hemolytic activity of the
      complex. Incubation of MCF-7 and Jurkat cells with OA, soluble or immobilized
      BAMLET resulted in increase in the uptake of Lyso Tracker Red and Nile red by the
      cells. The data presented support the contention that oleic acid plays the key
      role, both in BAMLET-induced hemolysis and tumoricidal action. 

PMID- 24039699
TI  - Identifying barriers to patient acceptance of active surveillance: content
      analysis of online patient communications.
AB  - OBJECTIVES: Qualitative research aimed at identifying patient acceptance of
      active surveillance (AS) has been identified as a public health research
      priority. The primary objective of this study was to determine if analysis of a
      large-sample of anonymous internet conversations (ICs) could be utilized to
      identify unmet public needs regarding AS. METHODS: English-language ICs regarding
      prostate cancer (PC) treatment with AS from 2002-12 were identified using a novel
      internet search methodology. Web spiders were developed to mine, aggregate, and
      analyze content from the world-wide-web for ICs centered on AS. Collection of ICs
      was not restricted to any specific geographic region of origin. NLP was used to
      evaluate content and perform a sentiment analysis. Conversations were scored as
      positive, negative, or neutral. A sentiment index (SI) was subsequently
      calculated according to the following formula to compare temporal trends in
      public sentiment towards AS: [(# Positive IC/#Total IC)-(#Negative IC/#Total IC)
      x 100]. RESULTS: A total of 464 ICs were identified. Sentiment increased from -13
      to +2 over the study period. The increase sentiment has been driven by increased
      patient emphasis on quality-of-life factors and endorsement of AS by national
      medical organizations. Unmet needs identified in these ICs include: a gap between
      quantitative data regarding long-term outcomes with AS vs. conventional
      treatments, desire for treatment information from an unbiased specialist, and
      absence of public role models managed with AS. CONCLUSIONS: This study
      demonstrates the potential utility of online patient communications to provide
      insight into patient preferences and decision-making. Based on our findings, we
      recommend that multidisciplinary clinics consider including an unbiased
      specialist to present treatment options and that future decision tools for AS
      include quantitative data regarding outcomes after AS.

PMID- 24039700
TI  - Breaking the link between environmental degradation and oil palm expansion: a
      method for enabling sustainable oil palm expansion.
AB  - Land degradation is a global concern. In tropical areas it primarily concerns the
      conversion of forest into non-forest lands and the associated losses of
      environmental services. Defining such degradation is not straightforward
      hampering effective reduction in degradation and use of already degraded lands
      for more productive purposes. To facilitate the processes of avoided degradation
      and land rehabilitation, we have developed a methodology in which we have used
      international environmental and social sustainability standards to determine the
      suitability of lands for sustainable agricultural expansion. The method was
      developed and tested in one of the frontiers of agricultural expansion, West
      Kalimantan province in Indonesia. The focus was on oil palm expansion, which is
      considered as a major driver for deforestation in tropical regions globally. The
      results suggest that substantial changes in current land-use planning are
      necessary for most new plantations to comply with international sustainability
      standards. Through visualizing options for sustainable expansion with our
      methodology, we demonstrate that the link between oil palm expansion and
      degradation can be broken. Application of the methodology with criteria and
      thresholds similar to ours could help the Indonesian government and the industry
      to achieve its pro-growth, pro-job, pro-poor and pro-environment development
      goals. For sustainable agricultural production, context specific guidance has to
      be developed in areas suitable for expansion. Our methodology can serve as a
      template for designing such commodity and country specific tools and deliver such
      guidance. 

PMID- 24039701
TI  - Simulating an infection growth model in certain healthy metabolic pathways of
      Homo sapiens for highlighting their role in Type I Diabetes mellitus using fire
      spread strategy, feedbacks and sensitivities.
AB  - Disease Systems Biology is an area of life sciences, which is not very well
      understood to date. Analyzing infections and their spread in healthy metabolite
      networks can be one of the focussed areas in this regard. We have proposed a
      theory based on the classical forest fire model for analyzing the path of
      infection spread in healthy metabolic pathways. The theory suggests that when
      fire erupts in a forest, it spreads, and the surrounding trees also catch fire.
      Similarly, when we consider a metabolic network, the infection caused in the
      metabolites of the network spreads like a fire. We have constructed a simulation
      model which is used to study the infection caused in the metabolic networks from
      the start of infection, to spread and ultimately combating it. For
      implementation, we have used two approaches, first, based on quantitative
      strategies using ordinary differential equations and second, using graph-theory
      based properties. Furthermore, we are using certain probabilistic scores to
      complete this task and for interpreting the harm caused in the network, given by
      a 'critical value' to check whether the infection can be cured or not. We have
      tested our simulation model on metabolic pathways involved in Type I Diabetes
      mellitus in Homo sapiens. For validating our results biologically, we have used
      sensitivity analysis, both local and global, as well as for identifying the role
      of feedbacks in spreading infection in metabolic pathways. Moreover, information
      in literature has also been used to validate the results. The metabolic network
      datasets have been collected from the Kyoto Encyclopedia of Genes and Genomes
      (KEGG). 

PMID- 24039702
TI  - 3.5A cryoEM structure of hepatitis B virus core assembled from full-length core
      protein.
AB  - The capsid shell of infectious hepatitis B virus (HBV) is composed of 240 copies
      of a single protein called HBV core antigen (HBc). An atomic model of a core
      assembled from truncated HBc was determined previously by X-ray crystallography.
      In an attempt to obtain atomic structural information of HBV core in a near
      native, non-crystalline environment, we reconstructed a 3.5A-resolution structure
      of a recombinant core assembled from full-length HBc by cryo electron microscopy
      (cryoEM) and derived an atomic model. The structure shows that the 240 molecules
      of full-length HBc form a core with two layers. The outer layer, composed of the
      N-terminal assembly domain, is similar to the crystal structure of the truncated
      HBc, but has three differences. First, unlike the crystal structure, our cryoEM
      structure shows no disulfide bond between the Cys61 residues of the two subunits
      within the dimer building block, indicating such bond is not required for core
      formation. Second, our cryoEM structure reveals up to four more residues in the
      linker region (amino acids 140-149). Third, the loops in the cryoEM structures
      containing this linker region in subunits B and C are oriented differently (~30
      degrees  and ~90 degrees ) from their counterparts in the crystal structure. The
      inner layer, composed of the C-terminal arginine-rich domain (ARD) and the ARD
      bound RNAs, is partially-ordered and connected with the outer layer through
      linkers positioned around the two-fold axes. Weak densities emanate from the rims
      of positively charged channels through the icosahedral three-fold and local three
      fold axes. We attribute these densities to the exposed portions of some ARDs,
      thus explaining ARD's accessibility by proteases and antibodies. Our data
      supports a role of ARD in mediating communication between inside and outside of
      the core during HBV maturation and envelopment. 

PMID- 24039703
TI  - Antigen-specific CD4 T cells are induced after intravesical BCG-instillation
      therapy in patients with bladder cancer and show similar cytokine profiles as in
      active tuberculosis.
AB  - Specific T cell immunity in patients with active tuberculosis is associated with
      a decrease in multifunctionality. However, it is unknown whether cytokine
      profiles differ in patients with primary infection and those with prior contact.
      We therefore used intravesical immunotherapy with attenuated live Bacille
      Calmette-Guerin (BCG) in patients with urothelial carcinoma as a model to
      characterise the induction of systemic immunity towards purified protein derivate
      (PPD) and to study whether cytokine profiles differ depending on pre-existing
      immunity. Eighteen patients with non-muscle invasive bladder cancer were
      recruited during the BCG-induction course. Fifty-four healthy individuals served
      as controls. Interferon (IFN)-gamma and interleukin (IL)-2 producing PPD-specific
      CD4 T cells were analysed longitudinally before each instillation using a rapid
      flow-cytometric whole blood immunoassay. Baseline levels of IFN-gamma producing
      PPD-specific T cells were comparable to controls. T cells showed a 5-fold
      increase to 0.23% by week 2/3, and further increased 8-fold by week 4/5 (to
      0.42%, p=0.0007). Systemic immunity was induced in all patients, although the
      increase was less pronounced in patients with pre-existing immunity. As in active
      TB, cytokine profiling during therapy revealed a lower percentage of
      multifunctional IFN-gamma/IL-2 double-positive T cells compared to controls
      (60.2% vs. 71.9%, p=0.0003). Of note, when comparing patients with and without
      pre-existing immunity, cytokine profiles in patients with primary immunity were
      shifted towards IL-2 single producing T cells (p=0.02), whereas those in patients
      with pre-existing immunity were shifted towards IFN-gamma single-positivity
      (p=0.01). In conclusion, systemic T cell responses were induced after BCG
      therapy, and their kinetics and cytokine profile depended on pre-existing
      immunity. Decreased functionality is a typical feature of specific immunity in
      both patients with active tuberculosis and BCG-therapy. Among patients with
      active infection, a shift towards IL-2 or IFN-gamma single-positive cells may
      allow distinction between patients with primary infection and cases with boosted
      immunity after prior contact, respectively. 

PMID- 24039704
TI  - Free HIV antiretroviral therapy enhances adherence among individuals on stable
      treatment: implications for potential shortfalls in free antiretroviral therapy.
AB  - OBJECTIVE: To estimate the population-level causal effect of source of payment
      for HIV medication on treatment adherence using Marginal Structural Models.
      METHODS: Data were obtained from an observational cohort of 76 HIV-infected
      individuals with at least 24 weeks of antiretroviral therapy treatment from 2002
      to 2007 in Kampala, Uganda. Adherence was the primary outcome and it was measured
      using the 30-day visual analogue scale. Marginal structural models (MSM) were
      used to estimate the effect of source of payment for HIV medication on adherence,
      adjusting for confounding by income, duration on antiretroviral therapy (ART),
      timing of visit, prior adherence, prior CD4+ T cell count and prior plasma HIV
      RNA. Traditional association models were also examined and the results compared.
      RESULTS: Free HIV treatment was associated with a 3.8% improvement in adherence
      in the marginal structural model, while the traditional statistical models showed
      a 3.1-3.3% improvement in adherence associated with free HIV treatment.
      CONCLUSION: Removing a financial barrier to treatment with ART by providing free
      HIV treatment appears to significantly improve adherence to antiretroviral
      therapy. With sufficient information on confounders, MSMs can be used to make
      robust inferences about causal effects in epidemiologic research.

PMID- 24039705
TI  - The crystal structure of the core domain of a cellulose induced protein (Cip1)
      from Hypocrea jecorina, at 1.5 A resolution.
AB  - In an effort to characterise the whole transcriptome of the fungus Hypocrea
      jecorina, cDNA clones of this fungus were identified that encode for previously
      unknown proteins that are likely to function in biomass degradation. One of these
      newly identified proteins, found to be co-regulated with the major H. jecorina
      cellulases, is a protein that was denoted Cellulose induced protein 1 (Cip1).
      This protein consists of a glycoside hydrolase family 1 carbohydrate binding
      module connected via a linker region to a domain with yet unknown function. After
      cloning and expression of Cip1 in H. jecorina, the protein was purified and
      biochemically characterised with the aim of determining a potential enzymatic
      activity for the novel protein. No hydrolytic activity against any of the tested
      plant cell wall components was found. The proteolytic core domain of Cip1 was
      then crystallised, and the three-dimensional structure of this was determined to
      1.5 A resolution utilising sulphur single-wavelength anomalous dispersion phasing
      (sulphor-SAD). A calcium ion binding site was identified in a sequence conserved
      region of Cip1 and is also seen in other proteins with the same general fold as
      Cip1, such as many carbohydrate binding modules. The presence of this ion was
      found to have a structural role. The Cip1 structure was analysed and a structural
      homology search was performed to identify structurally related proteins. The two
      published structures with highest overall structural similarity to Cip1 found
      were two poly-lyases: CsGL, a glucuronan lyase from H. jecorina and vAL-1, an
      alginate lyase from the Chlorella virus. This indicates that Cip1 may be a lyase.
      However, initial trials did not detect significant lyase activity for Cip1. Cip1
      is the first structure to be solved of the 23 currently known Cip1 sequential
      homologs (with a sequence identity cut-off of 25%), including both bacterial and
      fungal members. 

PMID- 24039706
TI  - The associations of single nucleotide polymorphisms in miR-146a, miR-196a and miR
      499 with breast cancer susceptibility.
AB  - BACKGROUND: Previous studies have investigated the association between single
      nucleotide polymorphisms (SNPs) located in microRNAs (miRNAs) and breast cancer
      susceptibility; however, because of their limited statistical power, many
      discrepancies are revealed in these studies. The meta-analysis presented here
      aimed to identify and characterize the roles of miRNA SNPs in breast cancer risk,
      and evaluate the associations of polymorphisms in miR-146a rs2910164, miR-196a
      rs11614913 and miR-499 rs3746444 with breast cancer susceptibility, respectively.
      METHODOLOGY/PRINCIPAL FINDINGS: The PubMed and Embases databases were searched
      updated to 31(st) December, 2012. The complete data of polymorphisms in miR-146a
      rs2910164, miR-196a rs11614913 and miR-499 rs3746444 from case-control studies
      for breast cancer were analyzed by odds ratios (ORs) with 95% confidence
      intervals (CIs) to reveal the associations of SNPs in miRNAs with breast cancer
      susceptibility. Totally, six studies for rs2910164 in miR-146a, involving 4225
      cases and 4469 controls; eight studies for rs11614913 in miR-196a, involving 4110
      cases and 5100 controls; and three studies of rs3746444 in miR-499, involving
      2588 cases and 3260 controls, were investigated in the meta-analysis. The
      rs11614913 (TT+CT) genotype of miR-196a2 was revealed to be associated with a
      decreased breast cancer susceptibility compared with the CC genotypes (OR =
      0.906, 95% CI: 0.825-0.995, P = 0.039); however, no significant associations were
      observed between rs2910164 in miR-146a (or rs3746444 in miR-499) and breast
      cancer susceptibility. CONCLUSIONS: This meta-analysis demonstrates the
      compelling evidence that the rs11614913 CC genotype in miR-196a2 increases breast
      cancer risk, which provides useful information for the early diagnosis and
      prevention of breast cancer.

PMID- 24039707
TI  - Whose mind matters more--the agent or the artist? An investigation of ethical and
      aesthetic evaluations.
AB  - Theory of mind, the capacity for reasoning about mental states such as beliefs
      and intentions, represents a critical input to ethical and aesthetic evaluations.
      Did the agent cause harm on purpose? Were those brushstrokes intentional? The
      current study investigates theory of mind for moral and artistic judgments within
      the same paradigm. In particular, we target the role of intent for two kinds of
      judgments: "objective" judgments of quality and "subjective" judgments of
      preference or liking. First, we show that intent matters more for objective
      versus subjective judgments in the case of ethics and aesthetics. Second, we show
      that, overall, intent matters more for ethical versus aesthetic evaluations.
      These findings suggest that an "objective-subjective" dimension describes
      judgments across both domains, and that observers assign more weight to the mind
      of the moral agent than the mind of the artist when making the relevant
      evaluations. 

PMID- 24039708
TI  - Relationship of the p22phox (CYBA) gene polymorphism C242T with risk of coronary
      artery disease: a meta-analysis.
AB  - BACKGROUND: Observational and experimental studies have thus far been unable to
      resolve whether the CYBA C242T polymorphism is associated with coronary artery
      disease (CAD). Therefore, we undertook a comprehensive meta-analysis to more
      precisely evaluate the influence of this polymorphism on CAD and potential
      biases. METHODS: We screened MEDLINE, Embase, CNKI, Wanfang and CBM up to January
      2013 and extracted data from 22 studies with 9,279 CAD patients and 9,349
      controls. A random-effects model was exploited to synthesize the inconsistent
      outcomes of the individual studies, while addressing between-study heterogeneity
      and publication bias. RESULTS: The CYBA C242T polymorphism conformed to Hard
      Weinberg Equilibrium for all studies (P>0.05). Overall comparison of the T allele
      with the C allele produced a non-significant risk estimate for CAD but with
      striking heterogeneity (T versus C: P = 0.87, OR = 0.99, 95%CI 0.89-1.11,
      P(heterogeneity)<0.0001, I2 = 67.8%). However, subgroup analysis by ethnicity
      documented that the T allele carriers had a marginal risk increase (21%) of CAD
      among Caucasians (recessive genetic model: P = 0.05, 95%CI 1.00-1.46,
      P(heterogeneity) = 0.15, I2 = 29.1%). Then data were divided into study design,
      the significance of CAD risk increase was substantially strengthened in matched
      case-control studies (allele comparison: P = 0.02, OR = 1.13, 95%CI 1.02-1.26,
      P(heterogeneity) = 0.24, I2 = 21.6%).Further meta-regression analysis identified
      that a large proportion of heterogeneity was explained by body mass index (BMI)
      (P = 0.03, OR = 1.07, 95%CI 1.01-1.15) and study design (P = 0.03, OR = 1.30,
      95%CI 1.02-1.64).There was no obvious publication bias as verified by funnel plot
      and Egger's linear regression test (t = -0.25, P = 0.81 for allele comparison).
      CONCLUSION: Taken together, our results suggested the CYBA C242T polymorphism
      might be a risk-conferring factor on developing CAD and BMI and study design were
      probable sources of between-study heterogeneity.

PMID- 24039709
TI  - Direct physical contact between intercalated cells in the distal convoluted
      tubule and the afferent arteriole in mouse kidneys.
AB  - Recent physiological studies in the kidney proposed the existence of a secondary
      feedback mechanism termed 'crosstalk' localized after the macula densa. This
      newly discovered crosstalk contact between the nephron tubule and its own
      afferent arteriole may potentially revolutionize our understanding of renal
      vascular resistance and electrolyte regulation. However, the nature of such a
      crosstalk mechanism is still debated due to a lack of direct and comprehensive
      morphological evidence. Its exact location along the nephron, its prevalence
      among the different types of nephrons, and the type of cells involved are yet
      unknown. To address these issues, computer assisted 3-dimensional nephron tracing
      was applied in combination with direct immunohistochemistry on plastic sections
      and electron microscopy. 'Random' contacts in the cortex were identified by the
      tracing and excluded. We investigated a total of 168 nephrons from all cortical
      regions. The results demonstrated that the crosstalk contact existed, and that it
      was only present in certain nephrons (90% of the short-looped and 75% of the long
      looped nephrons). The crosstalk contacts always occurred at a specific position-
      the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for
      the first time, that the cells found in the tubule wall at the contact site were
      always type nonA-nonB intercalated cells. In conclusion, the present work
      confirmed the existence of a post macula densa physical crosstalk contact.

PMID- 24039710
TI  - Myocardial injection of apelin-overexpressing bone marrow cells improves cardiac
      repair via upregulation of Sirt3 after myocardial infarction.
AB  - Our previous study shows that treatment with apelin increases bone marrow cells
      (BMCs) recruitment and promotes cardiac repair after myocardial infarction (MI).
      The objective of this study was to investigate whether overexpression of apelin
      in BMCs improved cell therapy and accelerated cardiac repair and functional
      recovery in post-MI mice. Mouse myocardial infarction was achieved by coronary
      artery ligation and BMCs overexpressing apelin (apelin-BMCs) or GFP (GFP-BMCs)
      were injected into ischemic area immediately after surgery. In vitro, exposure of
      cultured BMCs to apelin led to a gradual increase in SDF-1a and CXCR4 expression.
      Intramyocardial delivery of apelin-BMCs in post-MI mice resulted in a significant
      increase number of APJ+/c-kit+/Sca1+ cells in the injected area compared to GFP
      BMCs treated post-MI mice. Treatment with apelin-BMCs increased expression of
      VEGF, Ang-1 and Tie-2 in post-MI mice. Apelin-BMCs treatment also significantly
      increased angiogenesis and attenuated cardiac fibrosis formation in post-MI mice.
      Most importantly, treatment with apelin-BMCs significantly improved left
      ventricular (LV) systolic function in post-MI mice. Mechanistically, Apelin-BMCs
      treatment led to a significant increase in Sirtuin3 (Sirt3) expression and
      reduction of reactive oxygen species (ROS) formation. Treatment of cultured BMCs
      with apelin also increased Notch3 expression and Akt phosphorylation. Apelin
      treatment further attenuated stress-induced apoptosis whereas knockout of Sirt3
      abolished anti-apoptotic effect of apelin in cultured BMCs. Moreover, knockout of
      Sirt3 significantly attenuated apelin-BMCs-induced VEGF expression and
      angiogenesis in post-MI mice. Knockout of Sirt3 further blunted apelin-BMCs
      mediated improvement of cardiac repair and systolic functional recovery in post
      MI mice. These data suggest that apelin improves BMCs therapy on cardiac repair
      and systolic function in post-MI mice. Upregulation of Sirt3 may contribute to
      the protective effect of apelin-BMCs therapy.

PMID- 24039711
TI  - Setback distances as a conservation tool in wildlife-human interactions: testing
      their efficacy for birds affected by vehicles on open-coast sandy beaches.
AB  - In some wilderness areas, wildlife encounter vehicles disrupt their behaviour and
      habitat use. Changing driver behaviour has been proposed where bans on vehicle
      use are politically unpalatable, but the efficacy of vehicle setbacks and reduced
      speeds remains largely untested. We characterised bird-vehicle encounters in
      terms of driver behaviour and the disturbance caused to birds, and tested whether
      spatial buffers or lower speeds reduced bird escape responses on open beaches.
      Focal observations showed that: i) most drivers did not create sizeable buffers
      between their vehicles and birds; ii) bird disturbance was frequent; and iii)
      predictors of probability of flushing (escape) were setback distance and vehicle
      type (buses flushed birds at higher rates than cars). Experiments demonstrated
      that substantial reductions in bird escape responses required buffers to be wide
      (> 25 m) and vehicle speeds to be slow (< 30 km h-1). Setback distances can
      reduce impacts on wildlife, provided that they are carefully designed and derived
      from empirical evidence. No speed or distance combination we tested, however,
      eliminated bird responses. Thus, while buffers reduce response rates, they are
      likely to be much less effective than vehicle-free zones (i.e. beach closures),
      and rely on changes to current driver behaviour.

PMID- 24039712
TI  - Different cortical dynamics in face and body perception: an MEG study.
AB  - Evidence from functional neuroimaging indicates that visual perception of human
      faces and bodies is carried out by distributed networks of face and body
      sensitive areas in the occipito-temporal cortex. However, the dynamics of
      activity in these areas, needed to understand their respective functional roles,
      are still largely unknown. We monitored brain activity with millisecond time
      resolution by recording magnetoencephalographic (MEG) responses while
      participants viewed photographs of faces, bodies, and control stimuli. The
      cortical activity underlying the evoked responses was estimated with anatomically
      constrained noise-normalised minimum-norm estimate and statistically analysed
      with spatiotemporal cluster analysis. Our findings point to distinct
      spatiotemporal organization of the neural systems for face and body perception.
      Face-selective cortical currents were found at early latencies (120-200 ms) in a
      widespread occipito-temporal network including the ventral temporal cortex (VTC).
      In contrast, early body-related responses were confined to the lateral occipito
      temporal cortex (LOTC). These were followed by strong sustained body-selective
      responses in the orbitofrontal cortex from 200-700 ms, and in the lateral
      temporal cortex and VTC after 500 ms latency. Our data suggest that the VTC
      region has a key role in the early processing of faces, but not of bodies.
      Instead, the LOTC, which includes the extra-striate body area (EBA), appears the
      dominant area for early body perception, whereas the VTC contributes to late and
      post-perceptual processing. 

PMID- 24039714
TI  - Stratification requirements for seed dormancy alleviation in a wetland weed.
AB  - Echinochloaoryzicola(syn.E. phyllopogon) is an exotic weed of California rice
      paddies that has evolved resistance to multiple herbicides. Elimination of
      seedlingsthroughcertain weed control methods can limit the spread of this weed,
      but is contingent on accurate predictions of germination and emergence timing,
      which are influenced by seed dormancy levels.In summer annuals, dormancy can
      often be relieved through stratification, a period of prolonged exposure to cold
      and moist conditions.We used population-based threshold models to quantify the
      effects of stratification on seed germination of four E. Oryzicola populations at
      a range of water potential (Psi) and oxygen levels. We also determined how
      stratification temperatures, moisture levels and durations contributed to
      dormancy release. Stratification released dormancy by decreasing base Psi and
      hydrotimerequired for germination and by eliminating any germination sensitivity
      to oxygen. Stratification also increased average germination rates (GR), which
      were used as a proxy for relative dormancy levels. Alternating temperatures
      nearly doubled GR in all populations, indicating that seeds could be partially
      dormant despite achieving high final germination percentages. Stratification at
      Psi = 0 MPa increased GR compared to stratification at lower water potentials,
      demonstrating that Psi contributed to regulating dormancy release. Maximum GR
      occurred after 2-4 weeks of stratification at 0 MPa; GR were often more rapid for
      herbicide-resistant than for herbicide-susceptible seeds, implying greater
      dormancy in the latter. Manipulation of field conditions to promote dormancy
      alleviation of E. oryzicola seeds might improve the rate and uniformity of
      germination for seed bank depletion through seedling weed control. Our results
      suggest field soil saturation in winter would contribute towards E. oryzicola
      dormancy release and decrease the time to seedling emergence. 

PMID- 24039713
TI  - Abrogated thioredoxin system causes increased sensitivity to TNF-alpha-induced
      apoptosis via enrichment of p-ERK 1/2 in the nucleus.
AB  - Thioredoxin (Trx) and thioredoxin reductase 1 (TR1) are among the major redox
      regulators in mammalian cells and have a wide variety of roles, including removal
      of intracellular reactive oxygen species (ROS) and prevention of cell death.
      Tumor necrosis factor-alpha (TNF-alpha) induces cancer cell death. Although ROS
      have been proposed to participate in this process, the role of the thioredoxin
      system in TNF-alpha stimulated cell death remains unclear. We investigated the
      possibility that the thioredoxin system protects against TNF-alpha-induced cancer
      cell death by examining whether TR1/Trx1 status controls TNF-alpha-induced
      apoptosis in EMT6 murine breast cancer cells. TR1-deficient cells were more
      sensitive to TNF-alpha than control cells. Increased sensitivity to TNF-alpha was
      most pronounced in Trx1-deficient cells. TNF-alpha-induced nuclear localization
      of phosphorylated ERK 1/2 (p-ERK 1/2) correlated with increased apoptosis in TR1-
      and Trx1-deficient cells, suggesting a pro-apoptotic role for nuclear p-ERK 1/2
      in TNF-alpha-induced apoptosis. In addition, phosphoinositide 3-kinase (PI3K)
      inhibition dramatically reduced TNF-alpha-stimulated apoptosis and nuclear
      localization of p-ERK 1/2. In contrast, inhibition of ROS, MEK, JNK, or p38 did
      not significantly alter p-ERK 1/2 localization or apoptosis in TR1- and Trx1
      deficient cells compared to control cells. Further, NF-kappaB p65 localization
      was not changed in TR1- and Trx1-deficient cells in response to TNF-alpha
      relative to control cells. Our data suggest that the thioredoxin system plays a
      critical role in protecting against TNF-alpha-induced apoptosis by regulating the
      levels of nuclear p-ERK 1/2 in a PI3K-dependent manner. 

PMID- 24039715
TI  - Reduction in cerebral perfusion after heroin administration: a resting state
      arterial spin labeling study.
AB  - Heroin dependence is a chronic relapsing brain disorder, characterized by the
      compulsion to seek and use heroin. Heroin itself has a strong potential to
      produce subjective experiences characterized by intense euphoria, relaxation and
      release from craving. The neurofunctional foundations of these perceived effects
      are not well known. In this study, we have used pharmacological magnetic
      resonance imaging (phMRI) in 15 heroin-dependent patients from a stable heroin
      assisted treatment program to observe the steady state effects of heroin (60 min
      after administration). Patients were scanned in a cross-over and placebo
      controlled design. They received an injection of their regular dose of heroin or
      saline (placebo) before or after the scan. As phMRI method, we used a pulsed
      arterial spin labeling (ASL) sequence based on a flow-sensitive alternating
      inversion recovery (FAIR) spin labeling scheme combined with a single-shot 3D
      GRASE (gradient-spin echo) readout on a 3 Tesla scanner. Analysis was performed
      with Statistical Parametric Mapping (SPM 8), using a general linear model for
      whole brain comparison between the heroin and placebo conditions. We found that
      compared to placebo, heroin was associated with reduced perfusion in the left
      anterior cingulate cortex (ACC), the left medial prefrontal cortex (mPFC) and in
      the insula (both hemispheres). Analysis of extracted perfusion values indicate
      strong effect sizes and no gender related differences. Reduced perfusion in these
      brain areas may indicate self- and emotional regulation effects of heroin in
      maintenance treatment. 

PMID- 24039717
TI  - Phytoplankton cell size reduction in response to warming mediated by nutrient
      limitation.
AB  - Shrinking of body size has been proposed as one of the universal responses of
      organisms to global climate warming. Using phytoplankton as an experimental model
      system has supported the negative effect of warming on body-size, but it remains
      controversial whether the size reduction under increasing temperatures is a
      direct temperature effect or an indirect effect mediated over changes in size
      selective grazing or enhanced nutrient limitation which should favor smaller cell
      sizes. Here we present an experiment with a factorial combination of temperature
      and nutrient stress which shows that most of the temperature effects on
      phytoplankton cell size are mediated via nutrient stress. This was found both for
      community mean cell size and for the cell sizes of most species analyzed. At the
      highest level of nutrient stress, community mean cell size decreased by 46% per 
      degrees C, while it decreased only by 4.7% at the lowest level of nutrient
      stress. Individual species showed qualitatively the same trend, but shrinkage per
      degrees C was smaller. Overall, our results support the hypothesis that
      temperature effects on cell size are to a great extent mediated by nutrient
      limitation. This effect is expected to be exacerbated under field conditions,
      where higher temperatures of the surface waters reduce the vertical nutrient
      transport. 

PMID- 24039716
TI  - Two-step tuberculin skin testing in school-going adolescents with initial 0-4
      millimeter responses in a high tuberculosis prevalence setting in South India.
AB  - BACKGROUND: The utility of two-step tuberculin skin testing among adolescents in
      high tuberculosis prevalence settings is not well established. OBJECTIVES: To
      determine the proportion and determinants of a 0-4 mm response to an initial
      standard tuberculin skin test (TST) and evaluating 'boosting' with repeat
      testing. METHODS: Adolescents between 11 and 18 years attending schools/colleges
      underwent a TST; those with a response of between 0-4 mm had a repeat TST 1-4
      weeks later. RESULTS: Initial TST was done for 6608/6643 participants; 1257 (19%)
      developed a 0-4 mm response to the initial TST. Younger age and under-nutrition
      were more likely to be associated with a 0-4 mm response, while the presence of
      BCG (Bacillus Calmette Guerin) scar and higher socio-economic class were less
      likely to be associated with a 0-4 mm response. On repeat testing boosting was
      seen in 13.2% (145/1098; >= 6 mm over the initial test) while 4.3% showed
      boosting using a more conservative cutoff of a repeat TST >= 10 mm with an
      increment of at least 6 mm (47/1098). History of exposure to a tuberculosis (TB)
      case was associated with enhanced response. CONCLUSION: The proportion of
      adolescents who demonstrated boosting on two-step TST testing in our study was
      relatively low. As a result repeat testing did not greatly alter the prevalence
      of TST positivity. However, the two-step TST helps identify individuals who can
      potentially boost their immune response to a second test, and thus, prevents them
      from being misclassified as those with newly acquired infection, or tuberculin
      converters. While two-step tuberculin skin testing may have a limited role in
      population- level TST surveys, it may be useful where serial tuberculin testing
      needs to be performed to distinguish those who show an enhanced response or
      boosters from those who indeed have a new infection, or converters.

PMID- 24039718
TI  - Stress reaction in outer segments of photoreceptors after blue light irradiation.
AB  - The retina is prone to oxidative stress from many factors which are also involved
      in the pathogenesis of degenerative diseases. In this study, we used the
      application of blue light as a physiological stress factor. The aim of this study
      was to identify the major source of intracellular ROS that mediates blue light
      induced detrimental effects on cells which may lead to cytotoxicity. We
      hypothesized that outer segments are the major source of blue light induced ROS
      generation. In photoreceptors, nicotinamide adenine dinucleotide phosphate
      (NADPH) oxidase (Nox) enzymes and the recently found respiratory chain complexes
      may represent a major source for reactive oxygen species (ROS), beside
      mitochondria and chromophores. Therefore, we investigated this hypothesis and
      analysed the exact localization of the ROS source in photoreceptors in an
      organotypic culture system for mouse retinas. Whole eyeball cultures were
      irradiated with visible blue light (405 nm) with an output power of 1 mW/cm2.
      Blue light impingement lead to an increase of ROS production (detected by H2DCFDA
      in live retinal explants), which was particularly strong in the photoreceptor
      outer segments. Nox-2 and Nox-4 proteins are sources of ROS in blue light
      irradiated photoreceptors; the Nox inhibitor apocynin decreased ROS stimulated by
      blue light. Concomitantly, enzyme SOD-1, a member of the antioxidant defense
      system, indicator molecules of protein oxidation (CML) and lipid oxidation (MDA
      and 4-HNE) were also increased in the outer segments. Interestingly, outer
      segments showed a mitochondrial-like membrane potential which was demonstrated
      using two dyes (JC-1 and TMRE) normally exclusively associated with mitochondria.
      As in mitochondria, these dyes indicated a decrease of the membrane potential in
      hypoxic states or cell stress situations. The present study demonstrates that ROS
      generation and oxidative stress occurs directly in the outer segments of
      photoreceptors after blue light irradiation.

PMID- 24039719
TI  - Disruption of glycerol metabolism by RNAi targeting of genes encoding glycerol
      kinase results in a range of phenotype severity in Drosophila.
AB  - In Drosophila, RNAi targeting of either dGyk or dGK can result in two alternative
      phenotypes: adult glycerol hypersensitivity or larval lethality. Here we compare
      these two phenotypes at the level of glycerol kinase (GK) phosphorylation
      activity, dGyk and dGK-RNA expression, and glycerol levels. We found both
      phenotypes exhibit reduced but similar levels of GK phosphorylation activity.
      Reduced RNA expression levels of dGyk and dGK corresponded with RNAi progeny that
      developed into glycerol hypersensitive adult flies. However, quantification of
      dGyk/dGK expression levels for the larval lethality phenotype revealed unexpected
      levels possibly due to a compensatory mechanism between dGyk and dGK or RNAi
      inhibition. The enzymatic role of glycerol kinase converts glycerol to glycerol 3
      phosphate. As expected, elevated glycerol levels were observed in larvae that
      went on to develop into glycerol hypersensitive adults. Interestingly, larvae
      that died before eclosion revealed extremely low glycerol levels. Further
      characterization identified a wing phenotype that is enhanced by a dGpdh null
      mutation, indicating disrupted glycerol metabolism underlies the wing phenotype.
      In humans, glycerol kinase deficiency (GKD) exhibits a wide range of phenotypic
      variation with no obvious genotype-phenotype correlations. Additionally, disease
      severity often does not correlate with GK phosphorylation activity. It is
      intriguing that both human GKD patients and our GKD Drosophila model show a range
      of phenotype severity. Additionally, the lack of correlation between GK
      phosphorylation and dGyk/dGK-RNA expression with phenotypic severity suggests
      further study including understanding the alternative functions of the GK
      protein, could provide insights into the complex pathogenic mechanism observed in
      human GKD patients. 

PMID- 24039720
TI  - A new data-mining method to search for behavioral properties that induce
      alignment and their involvement in social learning in medaka fish (Oryzias
      latipes).
AB  - BACKGROUND: Coordinated movement in social animal groups via social learning
      facilitates foraging activity. Few studies have examined the behavioral cause-and
      effect between group members that mediates this social learning.
      METHODOLOGY/PRINCIPAL FINDINGS: We first established a behavioral paradigm for
      visual food learning using medaka fish and demonstrated that a single fish can
      learn to associate a visual cue with a food reward. Grouped medaka fish (6 fish)
      learn to respond to the visual cue more rapidly than a single fish, indicating
      that medaka fish undergo social learning. We then established a data-mining
      method based on Kullback-Leibler divergence (KLD) to search for candidate
      behaviors that induce alignment and found that high-speed movement of a focal
      fish tended to induce alignment of the other members locally and transiently
      under free-swimming conditions without presentation of a visual cue. The high
      speed movement of the informed and trained fish during visual cue presentation
      appeared to facilitate the alignment of naive fish in response to some visual
      cues, thereby mediating social learning. Compared with naive fish, the informed
      fish had a higher tendency to induce alignment of other naive fish under free
      swimming conditions without visual cue presentation, suggesting the involvement
      of individual recognition in social learning. CONCLUSIONS/SIGNIFICANCE:
      Behavioral cause-and-effect studies of the high-speed movement between fish group
      members will contribute to our understanding of the dynamics of social behaviors.
      The data-mining method used in the present study is a powerful method to search
      for candidates factors associated with inter-individual interactions using a
      dataset for time-series coordinate data of individuals.

PMID- 24039721
TI  - Irreversible electroporation of human primary uveal melanoma in enucleated eyes.
AB  - Uveal melanoma (UM) is the most common primary intraocular tumor in adults and is
      characterized by high rates of metastatic disease. Although brachytherapy is the
      most common globe-sparing treatment option for small- and medium-sized tumors,
      the treatment is associated with severe adverse reactions and does not lead to
      increased survival rates as compared to enucleation. The use of irreversible
      electroporation (IRE) for tumor ablation has potential advantages in the
      treatment of tumors in complex organs such as the eye. Following previous
      theoretical work, herein we evaluate the use of IRE for uveal tumor ablation in
      human ex vivo eye model. Enucleated eyes of patients with uveal melanoma were
      treated with short electric pulses (50-100 us, 1000-2000 V/cm) using a customized
      electrode design. Tumor bioimpedance was measured before and after treatment and
      was followed by histopathological evaluation. We found that IRE caused tumor
      ablation characterized by cell membrane disruption while sparing the non-cellular
      sclera. Membrane disruption and loss of cellular capacitance were also associated
      with significant reduction in total tumor impedance and loss of impedance
      frequency dependence. The effect was more pronounced near the pulsing electrodes
      and was dependent on time from treatment to fixation. Future studies should
      further evaluate the potential of IRE as an alternative method of uveal melanoma
      treatment. 

PMID- 24039722
TI  - Co-adaptation and the emergence of structure.
AB  - Co-adaptation (or co-evolution), the parallel feedback process by which agents
      continuously adapt to the changes induced by the adaptive actions of other
      agents, is a ubiquitous feature of complex adaptive systems, from eco-systems to
      economies. We wish to understand which general features of complex systems
      necessarily follow from the (meta)-dynamics of co-adaptation, and which features
      depend on the details of particular systems. To begin this project, we present a
      model of co-adaptation ("The Stigmergy Game") which is designed to be as a priori
      featureless as possible, in order to help isolate and understand the naked
      consequences of co-adaptation. In the model, heterogeneous, co-adapting agents,
      observe, interact with and change the state of an environment. Agents do not, ab
      initio, directly interact with each other. Agents adapt by choosing among a set
      of random "strategies," particular to each agent. Each strategy is a complete
      specification of an agent's actions and payoffs. A priori, all environmental
      states are equally likely and all strategies have payoffs that sum to zero, so
      without co-adaptation agents would on average have zero "wealth". Nevertheless,
      the dynamics of co-adaptation generates a structured environment in which only a
      subset of environmental states appear with high probability (niches) and in which
      agents accrue positive wealth. Furthermore, although there are no direct agent
      agent interactions, there are induced non-trivial inter-agent interactions
      mediated by the environment. As a function of the population size and the number
      of possible environmental states, the system can be in one of three dynamical
      regions. Implications for a basic understanding of complex adaptive systems are
      discussed. 

PMID- 24039723
TI  - A novel liquid medium for the efficient growth of the salmonid pathogen
      Piscirickettsia salmonis and optimization of culture conditions.
AB  - Piscirickettsia salmonis is the bacterium that causes Piscirickettsiosis, a
      systemic disease of salmonid fish responsible for significant economic losses
      within the aquaculture industry worldwide. The growth of the bacterium for
      vaccine formulation has been traditionally accomplished by infecting eukaryotic
      cell lines, a process that involves high production costs and is time-consuming.
      Recent research has demonstrated that it is possible to culture pure P. salmonis
      in a blood containing (cell-free) medium. In the present work we demonstrate the
      growth of P. salmonis in a liquid medium free from blood and serum components,
      thus establishing a novel and simplified bacteriological medium. Additionally,
      the new media reported provides improved growth conditions for P. salmonis, where
      biomass concentrations of approximately 800 mg cell dry weight L(-1) were
      obtained, about eight times higher than those reported for the blood containing
      medium. A 2- level full factorial design was employed to evaluate the
      significance of the main medium components on cell growth and an optimal
      temperature range of 23-27 degrees C was determined for the microorganism to grow
      in the novel liquid media. Therefore, these results represent a breakthrough
      regarding P. salmonis research in order to optimize pure P. salmonis growth in
      liquid blood and serum free medium. 

PMID- 24039724
TI  - First nationwide surveillance of Culex pipiens complex and Culex torrentium
      mosquitoes demonstrated the presence of Culex pipiens biotype pipiens/molestus
      hybrids in Germany.
AB  - Mosquitoes and other arthropods may transmit medically important pathogens, in
      particular viruses such as West Nile virus. The presence of suitable hosts and
      competent vectors for those zoonotic viruses is essential for an enzootic
      transmission, which is a prerequisite for epidemics. To establish reliable risk
      projections, it is an urgent need for an exact identification of mosquito
      species, which is especially challenging in the case of sibling species, such as
      Culex. pipiens pipiens biotypes pipiens and molestus. To facilitate detection of
      different Culex pipiens forms and their hybrids we established a multiplex real
      time PCR. Culex pipiens samples were obtained by egg raft collection and rearing
      until imago stage or adult sampling using CO2 baited traps and gravid traps. In
      total, we tested more than 16,500 samples collected all over Germany in the years
      2011 and 2012. The predominant species in Germany are Culex pipiens pipiens
      biotype pipiens and Culex. torrentium, but we also detected Culex pipiens pipiens
      biotype molestus and hybrids of the two pipiens biotypes at sites where both
      species occur sympatrically. This report of a potentially important bridge vector
      for West Nile virus might have major impact in the risk projections for West Nile
      virus in Germany. 

PMID- 24039725
TI  - Complete genomic DNA sequence of the East Asian spotted fever disease agent
      Rickettsia japonica.
AB  - Rickettsia japonica is an obligate intracellular alphaproteobacteria that causes
      tick-borne Japanese spotted fever, which has spread throughout East Asia. We
      determined the complete genomic DNA sequence of R. japonica type strain YH (VR
      1363), which consists of 1,283,087 base pairs (bp) and 971 protein-coding genes.
      Comparison of the genomic DNA sequence of R. japonica with other rickettsiae in
      the public databases showed that 2 regions (4,323 and 216 bp) were conserved in a
      very narrow range of Rickettsia species, and the shorter one was inserted in, and
      disrupted, a preexisting open reading frame (ORF). While it is unknown how the
      DNA sequences were acquired in R. japonica genomes, it may be a useful signature
      for the diagnosis of Rickettsia species. Instead of the species-specific inserted
      DNA sequences, rickettsial genomes contain Rickettsia-specific palindromic
      elements (RPEs), which are also capable of locating in preexisting ORFs. Precise
      alignments of protein and DNA sequences involving RPEs showed that when a gene
      contains an inserted DNA sequence, each rickettsial ortholog carried an inserted
      DNA sequence at the same locus. The sequence, ATGAC, was shown to be highly
      frequent and thus characteristic in certain RPEs (RPE-4, RPE-6, and RPE-7). This
      finding implies that RPE-4, RPE-6, and RPE-7 were derived from a common inserted
      DNA sequence. 

PMID- 24039726
TI  - Verticillium suppression is associated with the glucosinolate composition of
      Arabidopsis thaliana leaves.
AB  - The soil-borne fungal pathogen Verticillium longisporum is able to penetrate the
      root of a number of plant species and spread systemically via the xylem.
      Fumigation of Verticillium contaminated soil with Brassica green manure is used
      as an environmentally friendly method for crop protection. Here we present a
      study focused on the potential role of glucosinolates and their breakdown
      products of the model plant Arabidopsis thaliana in suppressing growth of V.
      longisporum. For this purpose we analysed the glucosinolate composition of the
      leaves and roots of a set of 19 key accessions of A. thaliana. The effect of
      volatile glucosinolate hydrolysis products on the in vitro growth of the pathogen
      was tested by exposing the fungus to hydrated lyophilized plant tissue. Volatiles
      released from leaf tissue were more effective than from root tissue in
      suppressing mycelial growth of V. longisporum. The accessions varied in their
      efficacy, with the most effective suppressing mycelial growth by 90%. An analysis
      of glucosinolate profiles and their enzymatic degradation products revealed a
      correlation between fungal growth inhibition and the concentration of alkenyl
      glucosinolates, particularly 2-propenyl (2Prop) glucosinolate, respectively its
      hydrolysis products. Exposure of the fungus to purified 2Prop glucosinolate
      revealed that its suppressive activity was correlated with its concentration.
      Spiking of 2Prop glucosinolate to leaf material of one of the least effective A.
      thaliana accessions led to fungal growth suppression. It is suggested that much
      of the inhibitory effect observed for the tested accessions can be explained by
      the accumulation of 2Prop glucosinolate. 

PMID- 24039727
TI  - Taxonomic and life history bias in herbicide resistant weeds: implications for
      deployment of resistant crops.
AB  - Evolved herbicide resistance (EHR) is an important agronomic problem and
      consequently a food security problem, as it jeopardizes herbicide effectiveness
      and increases the difficulty and cost of weed management. EHR in weeds was first
      reported in 1970 and the number of cases has accelerated dramatically over the
      last two decades. Despite 40 years of research on EHR, why some weeds evolve
      resistance and others do not is poorly understood. Here we ask whether weed
      species that have EHR are different from weeds in general. Comparing taxonomic
      and life history traits of weeds with EHR to a control group ("the world's worst
      weeds"), we found weeds with EHR significantly over-represented in certain plant
      families and having certain life history biases. In particular, resistance is
      overrepresented in Amaranthaceae, Brassicaceae and Poaceae relative to all weeds,
      and annuality is ca. 1.5 times as frequent in weeds with EHR as in the control
      group. Also, for perennial EHR weeds, vegetative reproduction is only 60% as
      frequent as in the control group. We found the same trends for subsets of weeds
      with EHR to acetolactate synthase (ALS), photosystem II (PSII), and 5
      enolpyruvylshikimate-3-phosphate (EPSP) synthase-inhibitor herbicides and with
      multiple resistance. As herbicide resistant crops (transgenic or not) are
      increasingly deployed in developing countries, the problems of EHR could increase
      in those countries as it has in the USA if the selecting herbicides are heavily
      applied and appropriate management strategies are not employed. Given our
      analysis, we make some predictions about additional species that might evolve
      resistance. 

PMID- 24039728
TI  - Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma
      cell lines.
AB  - 2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which
      possesses antiproliferative, antiangiogenic and antitumor properties. However,
      due to its limited biological accessibility, synthetic analogues have been
      synthesized and tested in attempt to develop drugs with improved oral
      bioavailability and efficacy. The aim of this study was to evaluate the
      antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2
      analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor
      negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25
      MUM) was conducted with an exposure time of 24 hours. Results obtained from
      crystal violet staining indicated that 0.5 MUM of all 3 compounds reduced the
      number of cells to 50%. Lactate dehydrogenase assay was used to assess
      cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8
      activity assays were used to investigate the possible occurrence of apoptosis.
      Tubulin polymerization assays were conducted to evaluate the influence of these
      sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence
      microscopy using labeled antibodies specific to tyrosinate and detyrosinated
      tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin
      dynamics. An insignificant increase in the level of lactate dehydrogenase release
      was observed in the compounds-treated cells. These sulphamoylated compounds
      caused a reduction in mitochondrial membrane potential, cytochrome c release and
      caspase 3 activation indicating apoptosis induction by means of the intrinsic
      pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed
      after exposure to these three sulphamoylated analogues. 

PMID- 24039729
TI  - CTR1 silencing inhibits angiogenesis by limiting copper entry into endothelial
      cells.
AB  - Increased levels of intracellular copper stimulate angiogenesis in human
      umbilical vein endothelial cells (HUVECs). Copper transporter 1 (CTR1) is a
      copper importer present in the cell membrane and plays a major role in copper
      transport. In this study, three siRNAs targeting CTR1 mRNA were designed and
      screened for gene silencing. HUVECs when exposed to 100 uM copper showed 3 fold
      increased proliferation, migration by 1.8-fold and tube formation by 1.8-fold.
      One of the designed CTR1 siRNA (si 1) at 10 nM concentration decreased
      proliferation by 2.5-fold, migration by 4-fold and tube formation by 2.8-fold.
      Rabbit corneal packet assay also showed considerable decrease in matrigel induced
      blood vessel formation by si 1 when compared to untreated control. The designed
      si 1 when topically applied inhibited angiogenesis. This can be further developed
      for therapeutic application.

PMID- 24039730
TI  - Improving case-based reasoning systems by combining k-nearest neighbour algorithm
      with logistic regression in the prediction of patients' registration on the renal
      transplant waiting list.
AB  - INTRODUCTION: Case-based reasoning (CBR) is an emerging decision making paradigm
      in medical research where new cases are solved relying on previously solved
      similar cases. Usually, a database of solved cases is provided, and every case is
      described through a set of attributes (inputs) and a label (output). Extracting
      useful information from this database can help the CBR system providing more
      reliable results on the yet to be solved cases. OBJECTIVE: We suggest a general
      framework where a CBR system, viz. K-Nearest Neighbour (K-NN) algorithm, is
      combined with various information obtained from a Logistic Regression (LR) model,
      in order to improve prediction of access to the transplant waiting list. METHODS:
      LR is applied, on the case database, to assign weights to the attributes as well
      as the solved cases. Thus, five possible decision making systems based on K-NN
      and/or LR were identified: a standalone K-NN, a standalone LR and three soft K-NN
      algorithms that rely on the weights based on the results of the LR. The
      evaluation was performed under two conditions, either using predictive factors
      known to be related to registration, or using a combination of factors related
      and not related to registration. RESULTS AND CONCLUSION: The results show that
      our suggested approach, where the K-NN algorithm relies on both weighted
      attributes and cases, can efficiently deal with non relevant attributes, whereas
      the four other approaches suffer from this kind of noisy setups. The robustness
      of this approach suggests interesting perspectives for medical problem solving
      tools using CBR methodology.

PMID- 24039731
TI  - Evaluation of truncated NhhA protein as a candidate meningococcal vaccine
      antigen.
AB  - NhhA (Neisseria hia homologue) is an outer membrane protein from Neisseria
      meningitidis, the causative agent of meningococcal disease. The protein is
      surface exposed and its expression in a wide range of meningococcal strains
      suggests it is a promising vaccine candidate. In addition, immunization of mice
      with outer membrane vesicles of strains that overexpress NhhA in conjunction with
      one of TbpA, Omp85 or NspA results in synergistic bactericidal responses. We
      previously showed that the NhhA sequence is highly conserved between strains,
      with the majority of the differences localized to four distinct variable regions
      located in the amino-terminal region of the mature protein. In this study, N.
      meningitidis strains were constructed that over-express wild-type NhhA. Strains
      expressing truncated versions of NhhA, with deletions from the amino-terminal
      region that removed the most variable regions, were also made. These expression
      strains were also modified so that immunodominant, phase- and antigenically
      variable outer membrane proteins were not expressed, truncated
      lipooligosaccharide (LOS) expression was genetically fixed (no phase
      variability), and capsular polysaccharide expression abolished. Outer membrane
      vesicles derived from these strains were used to immunize mice. As previously
      observed, a synergistic effect involving another antigen, TbpA, was required to
      demonstrate bactericidal activity. The highest bactericidal response against a
      heterologous strain was obtained with a truncated variant of NhhA. These results
      indicate that removal of (a) variable region(s) does not reduce bactericidal
      responses against NhhA, and that bactericidal targets exist in regions other than
      the variable N-teminus. This provides the basis for future examination of
      responses against truncated NhhA in protecting against heterologous NhhA strains,
      and further evaluation of truncated NhhA as a candidate for inclusion in a
      vaccine against all serogroups of N. meningitidis. 

PMID- 24039732
TI  - Prognostic relevance of changes in exercise test variables in pulmonary arterial
      hypertension.
AB  - INTRODUCTION: Exercise variables determined in patients with pulmonary arterial
      hypertension (PAH) at the time of diagnosis, predict survival. It is unknown
      whether upon treatment, subsequent changes in these exercise variables reflect
      improvements in survival. The aim of this study was to determine changes in
      exercise variables in PAH patients and to relate these changes to survival.
      METHODS: Baseline cardiopulmonary exercise test (CPET) variables and six-minute
      walk-distance (6MWD) were available from 65 idiopathic PAH patients (50 females;
      mean age 45+/-2yrs). The same variables were determined after treatment
      (13months) in a sub group of 43 patients. To estimate the association between
      changes in exercise variables and changes in cardiac function, right-ventricle
      ejection fraction (RVEF) was measured by cardiac MRI at baseline and after
      treatment in 34 patients. Mean follow-up time after the second CPET was 53
      (range: 4-111) months. Kaplan-Meier analysis was used to relate survival to
      baseline and treatment-associated changes in exercise variables. RESULTS:
      Survivors showed a significantly greater change in maximal oxygen uptake than non
      survivors and this change in aerobic capacity was significantly related to
      changes in RVEF. From baseline until the end of the study period, two patients
      underwent a lung transplantation and 19 patients died. Survival analysis showed
      that baseline 6MWD (p<0.0001), maximal heart rate (p<0.0001) and the slope
      relating ventilation with carbon dioxide production (p<=0.05) were significant
      predictors of survival, whereas baseline oxygen uptake and oxygen pulse held no
      predictive value. Treatment associated changes in 6MWD (p<0.01), maximal heart
      rate (p<0.05), oxygen uptake (p<0.001) and oxygen pulse predicted survival
      (p<0.05), whereas changes in the slope relating ventilation with carbon dioxide
      production did not. CONCLUSION: Exercise variables with prognostic significance
      when determined at baseline, retain their prognostic relevance after treatment.
      However, when changes in exercise variables upon treatment are considered, a
      different set of variables provides prognostic information.

PMID- 24039733
TI  - Stimulation of osteoclast formation by RANKL requires interferon regulatory
      factor-4 and is inhibited by simvastatin in a mouse model of bone loss.
AB  - Diseases of bone loss are a major public health problem. Here, we report the
      novel therapeutic action of simvastatin in osteoclastogenesis and
      osteoprotection, demonstrated by the ability of simvastatin to suppress
      osteoclast formation in vitro and in vivo. We found that in vitro, IRF4
      expression is upregulated during osteoclast differentiation induced by RANKL
      (receptor activator of nuclear factor-kappaB ligand), while simvastatin blocks
      RANKL-induced osteoclastogenesis and decreases expression of NFATc1 (nuclear
      factor of activated T-cells, cytoplasmic, calcineurin-dependent 1), IRF4 and
      osteoclast markers. We also show that IRF4 acts in cooperation with NFATc2 and NF
      kappaB on the promoter region of NFATc1 to accelerate its initial transcription
      during the early stage of osteoclastogenesis. Moreover, our study using IRF4
      siRNA knockdown directly demonstrates the requirement for IRF4 in NFATc1 mRNA
      transcription and its necessity in RANKL-induced osteoclast differentiation. Our
      results suggest that the reduction in osteoclastogenesis is partly due to the
      inhibition of IRF4 production in RANKL-induced osteoclast differentiation. To
      investigate the in vivo effects of simvastatin in RANKL-treated mice, we examined
      the bone mineral density (BMD) of a mouse model of bone loss, and found that
      simvastatin significantly reduced bone loss by suppressing osteoclast numbers in
      vivo, even in the presence of high concentrations of RANKL. These results suggest
      that the depletion of osteoclasts is not due to the reduction in RANKL produced
      by osteoblasts in vivo. The results are consistent with the hypothesis that
      simvastatin blocks RANKL-induced IRF4 expression in osteoclastogenesis. We
      propose that the expression of IRF4 by osteoclasts could be a promising new
      therapeutic target in bone-loss diseases. 

PMID- 24039734
TI  - Phenotypic alteration of neutrophils in the blood of HIV seropositive patients.
AB  - We have recently identified a novel population of activated low-density
      granulocytes (LDGs) in peripheral blood mononuclear cells of HIV seropositive
      patients. LDGs have a similar morphology to normal density granulocytes (NDGs),
      but are phenotypically different. Here we measured the expression levels of
      different phenotypic markers of granulocytes in the blood of HIV seropositive
      patients at different stages of HIV infection to determine whether the phenotype
      of NDGs and LDGs are affected by disease severity. Our results reveal that the
      phenotype of NDGs, but not that of LDGs, varies according to the severity of the
      disease. 

PMID- 24039735
TI  - Comparative evaluation of GenoType MTBDRplus line probe assay with solid culture
      method in early diagnosis of multidrug resistant tuberculosis (MDR-TB) at a
      tertiary care centre in India.
AB  - BACKGROUND: The objectives of the study were to compare the performance of line
      probe assay (GenoType MTBDRplus) with solid culture method for an early diagnosis
      of multidrug resistant tuberculosis (MDR-TB), and to study the mutation patterns
      associated with rpoB, katG and inhA genes at a tertiary care centre in north
      India. METHODS: In this cross-sectional study, 269 previously treated sputum
      smear acid-fast bacilli (AFB) positive MDR-TB suspects were enrolled from January
      to September 2012 at the All India Institute of Medical Sciences hospital, New
      Delhi. Line probe assay (LPA) was performed directly on the sputum specimens and
      the results were compared with that of conventional drug susceptibility testing
      (DST) on solid media [Lowenstein Jensen (LJ) method]. RESULTS: DST results by LPA
      and LJ methods were compared in 242 MDR-TB suspects. The LPA detected rifampicin
      (RIF) resistance in 70 of 71 cases, isoniazid (INH) resistance in 86 of 93 cases,
      and MDR-TB in 66 of 68 cases as compared to the conventional method. Overall
      (rifampicin, isoniazid and MDR-TB) concordance of the LPA with the conventional
      DST was 96%. Sensitivity and specificity were 98% and 99% respectively for
      detection of RIF resistance; 92% and 99% respectively for detection of INH
      resistance; 97% and 100% respectively for detection of MDR-TB. Frequencies of
      katG gene, inhA gene and combined katG and inhA gene mutations conferring all INH
      resistance were 72/87 (83%), 10/87 (11%) and 5/87 (6%) respectively. The
      turnaround time of the LPA test was 48 hours. CONCLUSION: The LPA test provides
      an early diagnosis of monoresistance to isoniazid and rifampicin and is highly
      sensitive and specific for an early diagnosis of MDR-TB. Based on these findings,
      it is concluded that the LPA test can be useful in early diagnosis of drug
      resistant TB in high TB burden countries.

PMID- 24039737
TI  - Effects of ionizing radiation on embryos of the tardigrade Milnesium cf.
      tardigradum at different stages of development.
AB  - Tardigrades represent one of the most desiccation and radiation tolerant animals
      on Earth, and several studies have documented their tolerance in the adult stage.
      Studies on tolerance during embryological stages are rare, but differential
      effects of desiccation and freezing on different developmental stages have been
      reported, as well as dose-dependent effect of gamma irradiation on tardigrade
      embryos. Here, we report a study evaluating the tolerance of eggs from the
      eutardigrade Milnesium cf. tardigradum to three doses of gamma radiation (50, 200
      and 500 Gy) at the early, middle, and late stage of development. We found that
      embryos of the middle and late developmental stages were tolerant to all doses,
      while eggs in the early developmental stage were tolerant only to a dose of 50
      Gy, and showed a declining survival with higher dose. We also observed a delay in
      development of irradiated eggs, suggesting that periods of DNA repair might have
      taken place after irradiation induced damage. The delay was independent of dose
      for eggs irradiated in the middle and late stage, possibly indicating a fixed
      developmental schedule for repair after induced damage. These results show that
      the tolerance to radiation in tardigrade eggs changes in the course of their
      development. The mechanisms behind this pattern are unknown, but may relate to
      changes in mitotic activities over the embryogenesis and/or to activation of
      response mechanisms to damaged DNA in the course of development. 

PMID- 24039738
TI  - A randomized controlled study on the effects of bisoprolol and atenolol on
      sympathetic nervous activity and central aortic pressure in patients with
      essential hypertension.
AB  - OBJECTIVE: beta-blockers (BBs) with different pharmacological properties may have
      heterogeneous effects on sympathetic nervous activity (SNA) and central aortic
      pressure (CAP), which are independent cardiovascular factors for hypertension.
      Hence, we analyzed the effects of bisoprolol and atenolol on SNA and CAP in
      hypertensive patients. METHODS: This was a prospective, randomized, controlled
      study in 109 never-treated hypertensive subjects randomized to bisoprolol (5 mg)
      or atenolol (50 mg) for 4-8 weeks. SNA, baroreflex sensitivity (BRS) and heart
      rate (HR) variability (HRV) were measured using power spectral analysis using a
      Finometer. CAP and related parameters were determined using the SphygmoCor device
      (pulse wave analysis). RESULTS: Both drugs were similarly effective in reducing
      brachial BP. However, central systolic BP (-14+/-10 mm Hg vs -6+/-9 mm Hg;
      P<0.001) and aortic pulse pressure (-3+/-10 mm Hg vs +3+/-8 mm Hg; P<0.001)
      decreased more significantly with bisoprolol than with atenolol. The augmentation
      index at a HR of 75 bpm (AIxatHR75) was significantly decreased (29%+/-11% to
      25%+/-12%; P = 0.026) in the bisoprolol group only. Furthermore, the change in
      BRS in the bisoprolol group (3.99+/-4.19 ms/mmHg) was higher than in the atenolol
      group (2.66+/-3.78 ms/mmHg), although not statistically significant (P>0.05). BRS
      was stable when RHR was controlled (RHR<=65 bpm), and the two treatments had
      similar effects on the low frequency/high frequency (HF) ratio and on HF.
      CONCLUSION: BBs seem to have different effects on arterial distensibility and
      compliance in hypertensive subjects. Compared with atenolol, bisoprolol may have
      a better effect on CAP. TRIAL REGISTRATION: ClinicalTrials.gov NCT01762436.

PMID- 24039736
TI  - Meta-analysis of mismatch repair polymorphisms within the cogent consortium for
      colorectal cancer susceptibility.
AB  - In the last four years, Genome-Wide Association Studies (GWAS) have identified
      sixteen low-penetrance polymorphisms on fourteen different loci associated with
      colorectal cancer (CRC). Due to the low risks conferred by known common variants,
      most of the 35% broad-sense heritability estimated by twin studies remains
      unexplained. Recently our group performed a case-control study for eight Single
      Nucleotide Polymorphisms (SNPs) in 4 CRC genes. The present investigation is a
      follow-up of that study. We have genotyped six SNPs that showed a positive
      association and carried out a meta-analysis based on eight additional studies
      comprising in total more than 8000 cases and 6000 controls. The estimated
      recessive odds ratio for one of the SNPs, rs3219489 (MUTYH Q338H), decreased from
      1.52 in the original Swedish study, to 1.18 in the Swedish replication, and to
      1.08 in the initial meta-analysis. Since the corresponding summary probability
      value was 0.06, we decided to retrieve additional information for this
      polymorphism. The incorporation of six further studies resulted in around 13000
      cases and 13000 controls. The newly updated OR was 1.03. The results from the
      present large, multicenter study illustrate the possibility of decreasing effect
      sizes with increasing samples sizes. Phenotypic heterogeneity, differential
      environmental exposures, and population specific linkage disequilibrium patterns
      may explain the observed difference of genetic effects between Sweden and the
      other investigated cohorts. 

PMID- 24039739
TI  - Structure determination and biochemical characterization of a putative HNH
      endonuclease from Geobacter metallireducens GS-15.
AB  - The crystal structure of a putative HNH endonuclease, Gmet_0936 protein from
      Geobacter metallireducens GS-15, has been determined at 2.6 A resolution using
      single-wavelength anomalous dispersion method. The structure contains a two
      stranded anti-parallel beta-sheet that are surrounded by two helices on each
      face, and reveals a Zn ion bound in each monomer, coordinated by residues Cys38,
      Cys41, Cys73, and Cys76, which likely plays an important structural role in
      stabilizing the overall conformation. Structural homologs of Gmet_0936 include
      Hpy99I endonuclease, phage T4 endonuclease VII, and other HNH endonucleases, with
      these enzymes sharing 15-20% amino acid sequence identity. An overlay of
      Gmet_0936 and Hpy99I structures shows that most of the secondary structure
      elements, catalytic residues as well as the zinc binding site (zinc ribbon) are
      conserved. However, Gmet_0936 lacks the N-terminal domain of Hpy99I, which
      mediates DNA binding as well as dimerization. Purified Gmet_0936 forms dimers in
      solution and a dimer of the protein is observed in the crystal, but with a
      different mode of dimerization as compared to Hpy99I. Gmet_0936 and its N77H
      variant show a weak DNA binding activity in a DNA mobility shift assay and a weak
      Mn2+-dependent nicking activity on supercoiled plasmids in low pH buffers. The
      preferred substrate appears to be acid and heat-treated DNA with AP sites,
      suggesting Gmet_0936 may be a DNA repair enzyme.

PMID- 24039740
TI  - Endocytic mechanism of internalization of dietary peptide lunasin into
      macrophages in inflammatory condition associated with cardiovascular disease.
AB  - Cardiovascular disease (CVD) is the leading cause of death in the United States.
      Diet influences risk factors associated with CVD and atherosclerosis, a major
      vascular disease that arises from inflammation. Lunasin, a peptide derived from
      plant foods such as soybeans, contains a unique Arg-Gly-Asp cell-adhesion motif
      and inhibits the pathways involved in the inflammatory cascade. The objective was
      to determine the mechanism by which lunasin is internalized into human THP-1
      macrophages, investigate the expression of endocytic membrane proteins in
      inflammatory conditions and to identify the pathways involved. While
      lipopolysaccharide (10 nM), vitronectin (130 nM) and a combination of these two
      molecules enhanced lunasin uptake and increased basal alphaVbeta3 integrin
      expression, lunasin reduced alphaVbeta3 expression by 25.5, 26.8 and 49.2%,
      respectively. The pretreatment of cells with brefeldin A (71 uM), an inhibitor of
      protein trafficking, inhibited lunasin internalization by up to 99.8%. Lunasin
      increased caveolin-1 expression by up to 204.8%, but did not modulate clathrin.
      The pretreatment of macrophages with nystatin (54 uM), an inhibitor of caveolae
      dependent endocytosis, reduced lunasin internalization. The presence of
      amantadine (1 mM) and amiloride (1 mM), inhibitors of clathrin-mediated
      endocytosis and macropinocytosis, abolished lunasin cell entry. Lunasin elicited
      a transient reduction in intracellular levels of Ca2+ in LPS-induced macrophages.
      The results suggest that internalization of lunasin into macrophages is amplified
      in inflammatory conditions and is primarily mediated by endocytic mechanisms that
      involve integrin signaling, clathrin-coated structures and macropinosomes.
      Lunasin may be responsible for attenuation of CVD risk factors by interacting
      with pathways involved in endocytosis and inflammation.

PMID- 24039741
TI  - Role of endocytosis in localization and maintenance of the spatial markers for
      bud-site selection in yeast.
AB  - The yeast Saccharomyces cerevisiae normally selects bud sites (and hence axes of
      cell polarization) in one of two distinct patterns, the axial pattern of haploid
      cells and the bipolar pattern of diploid cells. These patterns depend on distinct
      sets of cortical-marker proteins that transmit positional information through a
      common signaling pathway based on a Ras-type GTPase. It has been reported
      previously that various proteins of the endocytic pathway may be involved in
      determining the bipolar pattern but not the axial pattern. To explore this
      question systematically, we constructed and analyzed congenic haploid and diploid
      deletion mutants for 14 genes encoding proteins that are involved in endocytosis.
      The mutants displayed a wide range of severities in their overall endocytosis
      defects, as judged by their growth rates and abilities to take up the lipophilic
      dye FM 4-64. Consistent with the previous reports, none of the mutants displayed
      a significant defect in axial budding, but they displayed defects in bipolar
      budding that were roughly correlated with the severities of their overall
      endocytosis defects. Both the details of the mutant budding patterns and direct
      examination of GFP-tagged marker proteins suggested that both initial formation
      and maintenance of the normally persistent bipolar marks depend on endocytosis,
      as well as polarized exocytosis, in actively growing cells. Interestingly,
      maintenance of the bipolar marks in non-growing cells did not appear to require
      normal levels of endocytosis. In some cases, there was a striking lack of
      correlation between the overall severities of the general-endocytosis defect and
      the bud-site selection defect, suggesting that various endocytosis proteins may
      differ in their importance for the uptake of various plasma-membrane targets. 

PMID- 24039742
TI  - Combining path integration and remembered landmarks when navigating without
      vision.
AB  - This study investigated the interaction between remembered landmark and path
      integration strategies for estimating current location when walking in an
      environment without vision. We asked whether observers navigating without vision
      only rely on path integration information to judge their location, or whether
      remembered landmarks also influence judgments. Participants estimated their
      location in a hallway after viewing a target (remembered landmark cue) and then
      walking blindfolded to the same or a conflicting location (path integration cue).
      We found that participants averaged remembered landmark and path integration
      information when they judged that both sources provided congruent information
      about location, which resulted in more precise estimates compared to estimates
      made with only path integration. In conclusion, humans integrate remembered
      landmarks and path integration in a gated fashion, dependent on the congruency of
      the information. Humans can flexibly combine information about remembered
      landmarks with path integration cues while navigating without visual information.

PMID- 24039743
TI  - Comprehensive analysis of genic male sterility-related genes in Brassica rapa
      using a newly developed Br300K oligomeric chip.
AB  - To identify genes associated with genic male sterility (GMS) that could be useful
      for hybrid breeding in Chinese cabbage (Brassicarapa ssp. pekinensis), floral bud
      transcriptome analysis was carried out using a B. rapa microarray with 300,000
      probes (Br300K). Among 47,548 clones deposited on a Br300K microarray with seven
      probes of 60 nt length within the 3' 150 bp region, a total of 10,622 genes were
      differentially expressed between fertile and sterile floral buds; 4,774 and 5,848
      genes were up-regulated over 2-fold in fertile and sterile buds, respectively.
      However, the expression of 1,413 and 199 genes showed fertile and sterile bud
      specific features, respectively. Genes expressed specifically in fertile buds,
      possibly GMS-related genes, included homologs of several Arabidopsis male
      sterility-related genes, genes associated with the cell wall and synthesis of its
      surface proteins, pollen wall and coat components, signaling components, and
      nutrient supplies. However, most early genes for pollen development, genes for
      primexine and callose formation, and genes for pollen maturation and anther
      dehiscence showed no difference in expression between fertile and sterile buds.
      Some of the known genes associated with Arabidopsis pollen development showed
      similar expression patterns to those seen in this study, while others did not.
      BrbHLH89 and BrMYP99 are putative GMS genes. Additionally, 17 novel genes
      identified only in B. rapa were specifically and highly expressed only in fertile
      buds, implying the possible involvement in male fertility. All data suggest that
      Chinese cabbage GMS might be controlled by genes acting in post-meiotic tapetal
      development that are different from those known to be associated with Arabidopsis
      male sterility. 

PMID- 24039744
TI  - Frequency and variability of genomic rearrangements on MSH2 in Spanish Lynch
      Syndrome families.
AB  - Large genomic rearrangements (LGRs) in DNA-mismatch-repair (MMR) genes,
      particularly among MSH2 gene, are frequently involved in the etiology of Lynch
      syndrome (LS). The Multiplex Ligation and Probe Amplification assay (MLPA) is
      commonly used to identify such alterations. However, in most cases, the MLPA
      identified alteration is not characterized at the molecular level, which might be
      important to identify recurrent alterations and to analyze the molecular
      mechanisms underlying these mutational events. Probands from a cohort of Lynch
      Syndrome families were screened for point mutation in MMR genes, subsequently the
      MLPA assay was used for LGR screening. The identified MLPA alteration was
      confirmed by cDNA, CGH-microarrays or massive parallel sequencing. In this study,
      we have delimited the region of 11 LGRs variants on MSH2 locus. Six of them were
      fully characterized the breakpoints and 9 of them were considered pathogenic.
      According to our data, LGR on MSH2 locus constituted the 10.8% (9 out of 83) of
      pathogenic germline alterations found in LS. The frequency of colorectal cancer
      (CRC) and endometrial cancer (EC) in LGR carriers was 55% and 11% respectively.
      Analysis of the breakpoint sequences revealed that in 3 cases, deletions appeared
      to originate from Alu-mediated recombination events. In the remaining cases,
      sequence alignment failed to detect microhomology around the breakpoints. The
      present study provides knowledge on the molecular characterization of MSH2 LGRs,
      which may have important implications in LS diagnosis and Genetic Counseling. In
      addition, our data suggests that nonhomologous events would be more frequently
      involved in the etiology of MSH2 LGRs than expected. 

PMID- 24039746
TI  - Replicate phylogenies and post-glacial range expansion of the pitcher-plant
      mosquito, Wyeomyia smithii, in North America.
AB  - Herein we tested the repeatability of phylogenetic inference based on high
      throughput sequencing by increased taxon sampling using our previously published
      techniques in the pitcher-plant mosquito, Wyeomyia smithii in North America. We
      sampled 25 natural populations drawn from different localities nearby 21 previous
      collection localities and used these new data to construct a second, independent
      phylogeny, expressly to test the reproducibility of phylogenetic patterns.
      Comparison of trees between the two data sets based on both maximum parsimony and
      maximum likelihood with Bayesian posterior probabilities showed close
      correspondence in the grouping of the most southern populations into clear
      clades. However, discrepancies emerged, particularly in the middle of W.
      smithii's current range near the previous maximum extent of the Laurentide Ice
      Sheet, especially concerning the most recent common ancestor to mountain and
      northern populations. Combining all 46 populations from both studies into a
      single maximum parsimony tree and taking into account the post-glacial historical
      biogeography of associated flora provided an improved picture of W. smithii's
      range expansion in North America. In a more general sense, we propose that
      extensive taxon sampling, especially in areas of known geological disruption is
      key to a comprehensive approach to phylogenetics that leads to biologically
      meaningful phylogenetic inference. 

PMID- 24039745
TI  - Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing
      responses.
AB  - BACKGROUND: The development of an effective AIDS vaccine has been a formidable
      task, but remains a critical necessity. The well conserved membrane-proximal
      external region (MPER) of the HIV-1 gp41 glycoprotein is one of the crucial
      targets for AIDS vaccine development, as it has the necessary attribute of being
      able to elicit antibodies capable of neutralizing diverse isolates of HIV.
      METHODOLOGY/PRINCIPLE FINDINGS: Guided by X-ray crystallography, molecular
      modeling, combinatorial chemistry, and powerful selection techniques, we designed
      and produced six combinatorial libraries of chimeric human rhinoviruses (HRV)
      displaying the MPER epitopes corresponding to mAbs 2F5, 4E10, and/or Z13e1,
      connected to an immunogenic surface loop of HRV via linkers of varying lengths
      and sequences. Not all libraries led to viable chimeric viruses with the desired
      sequences, but the combinatorial approach allowed us to examine large numbers of
      MPER-displaying chimeras. Among the chimeras were five that elicited antibodies
      capable of significantly neutralizing HIV-1 pseudoviruses from at least three
      subtypes, in one case leading to neutralization of 10 pseudoviruses from all six
      subtypes tested. CONCLUSIONS: Optimization of these chimeras or closely related
      chimeras could conceivably lead to useful components of an effective AIDS
      vaccine. While the MPER of HIV may not be immunodominant in natural infection by
      HIV-1, its presence in a vaccine cocktail could provide critical breadth of
      protection.

PMID- 24039747
TI  - Nanodiscs allow phage display selection for ligands to non-linear epitopes on
      membrane proteins.
AB  - In this work, we exploited a method that uses polytopic membrane proteins as
      targets for phage display selections. Membrane proteins represent the largest
      class of drug targets and drug discovery is mostly based on the identification of
      ligands binding to target molecules. The screening of a phage display library for
      ligands against membrane proteins is typically hindered by the requirement of
      these proteins for a membrane environment, which is necessary to retain correct
      folding and epitope formation. Especially in proteins with multiple transmembrane
      domains, epitopes often are non-linear and consist of a combination of loops
      between transmembrane stretches of the proteins. Here, we have used
      bacteriorhodopsin (bR) as a model of polytopic membrane protein, assembled into
      nanoscale phospholipid bilayers, so called nanodiscs, to screen a phage display
      library for potential ligands. Nanodiscs provide a native-like environment to
      membrane proteins and thus selection of ligands can take place in a near
      physiological state. Screening a 12-mer phage display peptide library against bR
      nanodiscs led to the isolation of phage clones binding specifically to bR. We
      were further able to identify the binding site of selected phage clones proving
      that the clones bind to extramembranous, non-linear epitopes of bR. Thus,
      nanodiscs provide a suitable and general tool that allows screening of a phage
      display library against membrane proteins in a near native environment. 

PMID- 24039748
TI  - Genetic and phenotypic selection affect natural (auto-) antibody reactivity of
      chickens.
AB  - Specificity, antibody isotype distribution and levels of natural antibodies (NAb)
      may be potential informative parameters for immune mediated natural disease
      resistance, immune modulation, and maintenance of physiological homeostasis. A
      large proportion of mammalian NAb have affinity for or are directed against self
      antigens; so called natural auto antibodies (N(A)Ab). In the present study we
      showed the presence and typed levels and isotypes (total immunoglobulins, IgG and
      IgM) of N(A)Ab in plasma binding the 'auto-antigen' complex chicken liver cell
      lysate (CLL) of one-year old chickens from different genotype and phenotype
      backgrounds by ELISA and quantitative Western blotting. Higher levels of N(A)Ab
      binding CLL were found in plasma from chickens genetically selected for high
      specific antibody responses. In all birds, extensive staining patterns of plasma
      antibodies binding CLL were found for all isotypes, with IgG binding the highest
      number of CLL antigens and also showing the highest variation in staining
      patterns between individuals. Patterns of IgM antibodies binding CLL appeared to
      be more similar in all lines. Significant differences of binding patterns of
      N(A)Ab (antigen fragments of CLL and staining intensity) were detected between
      the different chicken lines, and lines could be clustered on the basis of their
      auto-antibody profile. In addition, also individual differences within lines were
      found. The present results indicate that analysis of the levels and the N(A)Ab
      repertoire of poultry like in mammals could provide a new way of distinguishing
      differences of immune competence and immune maturation between individuals, and
      could provide tools to select birds for health traits, or optimize hygiene and
      husbandry procedures. 

PMID- 24039749
TI  - Continuous influenza virus production in cell culture shows a periodic
      accumulation of defective interfering particles.
AB  - Influenza viruses are a major public health burden during seasonal epidemics and
      a continuous threat due to their potential to cause pandemics. Annual vaccination
      provides the best protection against the contagious respiratory illness caused by
      influenza viruses. However, the current production capacities for influenza
      vaccines are insufficient to meet the increasing demands. We explored the
      possibility to establish a continuous production process for influenza viruses
      using the duck-derived suspension cell line AGE1.CR. A two-stage bioreactor setup
      was designed in which cells were cultivated in a first stirred tank reactor where
      an almost constant cell concentration was maintained. Cells were then constantly
      fed to a second bioreactor where virus infection and replication took place.
      Using this two-stage reactor system, it was possible to continuously produce
      influenza viruses. Surprisingly, virus titers showed a periodic increase and
      decrease during the run-time of 17 days. These titer fluctuations were caused by
      the presence of defective interfering particles (DIPs), which we detected by PCR.
      Mathematical modeling confirmed this observation showing that constant virus
      titers can only emerge in the absence of DIPs. Even with very low amounts of DIPs
      in the seed virus and very low rates for de novo DIP generation, defective
      viruses rapidly accumulate and, therefore, represent a serious challenge for
      continuous vaccine production. Yet, the continuous replication of influenza virus
      using a two-stage bioreactor setup is a novel tool to study aspects of viral
      evolution and the impact of DIPs. 

PMID- 24039750
TI  - Comparison of stress-induced changes in adults and pups: is aldosterone the main
      adrenocortical stress hormone during the perinatal period in rats?
AB  - Positive developmental impact of low stress-induced glucocorticoid levels in
      early development has been recognized for a long time, while possible involvement
      of mineralocorticoids in the stress response during the perinatal period has been
      neglected. The present study aimed at verifying the hypothesis that balance
      between stress-induced glucocorticoid and mineralocorticoid levels is changing
      during postnatal development. Hormone responses to two different stressors
      (insulin-induced hypoglycaemia and immune challenge induced by bacterial
      lipopolysaccharid) measured in 10-day-old rats were compared to those in adults.
      In pups corticosterone responses to both stressors were significantly lower than
      in adults, which corresponded well with the stress hyporesponsive period.
      Importantly, stress-induced elevations in aldosterone concentration were
      significantly higher in pups compared both to corticosterone elevations and to
      those in adulthood with comparable adrenocorticotropin concentrations in the two
      age groups. Greater importance of mineralocorticoids compared to glucocorticoids
      in postnatal period is further supported by changes in gene expression and
      protein levels of gluco- (GR) and mineralocorticoid receptors (MR) and selected
      enzymes measured by quantitative PCR and immunohystochemistry in the
      hypothalamus, hippocampus, prefrontal cortex, liver and kidney. Gene expression
      of 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2), an enzyme enabling
      preferential effects of aldosterone on mineralocorticoid receptors, was higher in
      10-day-old pups compared to adult animals. On the contrary, the expression and
      protein levels of GR, MR and 11beta-HSD1 were decreased. Presented results
      clearly show higher stress-induced release of aldosterone in pups compared to
      adults and strongly suggest greater importance of mineralocorticoids compared to
      glucocorticoids in stress during the postnatal period. 

PMID- 24039751
TI  - Genomics study of the exposure effect of Gymnodinium catenatum, a paralyzing
      toxin producer, on Crassostrea gigas' defense system and detoxification genes.
AB  - BACKGROUND: Crassostrea gigas accumulates paralytic shellfish toxins (PST)
      associated with red tide species as Gymnodinium catenatum. Previous studies
      demonstrated bivalves show variable feeding responses to toxic algae at
      physiological level; recently, only one study has reported biochemical changes in
      the transcript level of the genes involved in C. gigas stress response. PRINCIPAL
      FINDINGS: We found that 24 h feeding on toxic dinoflagellate cells (acute
      exposure) induced a significant decrease in clearance rate and expression level
      changes of the genes involved in antioxidant defense (copper/zinc superoxide
      dismutase, Cu/Zn-SOD), cell detoxification (glutathione S-transferase, GST and
      cytochrome P450, CPY450), intermediate immune response activation
      (lipopolysaccharide and beta glucan binding protein, LGBP), and stress responses
      (glutamine synthetase, GS) in Pacific oysters compared to the effects with the
      non-toxic microalga Isochrysis galbana. A sub-chronic exposure feeding on toxic
      dinoflagellate cells for seven and fourteen days (30*103 cells mL-1) showed
      higher gene expression levels. A significant increase was observed in Cu/Zn-SOD,
      GST, and LGBP at day 7 and a major increase in GS and CPY450 at day 14. We also
      observed that oysters fed only with G. catenatum (3*103 cells mL-1 produced a
      significant increase on the transcription level than in a mixed diet (3*103 cells
      mL-1 of G. catenatum+0.75*106 cells mL-1 I. galbana) in all the analyzed genes.
      CONCLUSIONS: Our results provide gene expression data of PST producer
      dinoflagellate G. catenatum toxic effects on C. gigas, a commercially important
      bivalve. Over expressed genes indicate the activation of a potent protective
      mechanism, whose response depends on both cell concentration and exposure time
      against these toxic microalgae. Given the importance of dinoflagellate blooms in
      coastal environments, these results provide a more comprehensive overview of how
      oysters respond to stress generated by toxic dinoflagellate exposure.

PMID- 24039752
TI  - C-element: a new clustering algorithm to find high quality functional modules in
      PPI networks.
AB  - Graph clustering algorithms are widely used in the analysis of biological
      networks. Extracting functional modules in protein-protein interaction (PPI)
      networks is one such use. Most clustering algorithms whose focuses are on finding
      functional modules try either to find a clique like sub networks or to grow
      clusters starting from vertices with high degrees as seeds. These algorithms do
      not make any difference between a biological network and any other networks. In
      the current research, we present a new procedure to find functional modules in
      PPI networks. Our main idea is to model a biological concept and to use this
      concept for finding good functional modules in PPI networks. In order to evaluate
      the quality of the obtained clusters, we compared the results of our algorithm
      with those of some other widely used clustering algorithms on three high
      throughput PPI networks from Sacchromyces Cerevisiae, Homo sapiens and
      Caenorhabditis elegans as well as on some tissue specific networks. Gene Ontology
      (GO) analyses were used to compare the results of different algorithms. Each
      algorithm's result was then compared with GO-term derived functional modules. We
      also analyzed the effect of using tissue specific networks on the quality of the
      obtained clusters. The experimental results indicate that the new algorithm
      outperforms most of the others, and this improvement is more significant when
      tissue specific networks are used. 

PMID- 24039753
TI  - Environmental factors predicting blood lead levels in pregnant women in the UK:
      the ALSPAC study.
AB  - BACKGROUND: Lead is a widespread environmental toxin. The behaviour and academic
      performance of children can be adversely affected even at low blood lead levels
      (BLL) of 5-10 ug/dl. An important contribution to the infant's lead load is
      provided by maternal transfer during pregnancy. OBJECTIVES: Our aim was to
      determine BLL in a large cohort of pregnant women in the UK and to identify the
      factors that contribute to BLL in pregnant women. METHODS: Pregnant women
      resident in the Avon area of the UK were enrolled in the Avon Longitudinal Study
      of Parents and Children (ALSPAC) in 1991-1992. Whole blood samples were collected
      at median gestational age of 11 weeks and analysed by inductively coupled plasma
      dynamic reaction cell mass spectrometry (n = 4285). Self-completion postal
      questionnaires were used to collect data during pregnancy on lifestyle, diet and
      other environmental exposures. Statistical analysis was carried out with SPSS
      v19. RESULTS: The mean+/-SD BLL was 3.67+/-1.47 (median 3.41, range 0.41-19.14)
      ug/dl. Higher educational qualification was found to be one of the strongest
      independent predictor of BLL in an adjusted backwards stepwise logistic
      regression to predict maternal BLL <5 or >=5 ug/dl (odds ratio 1.26, 95%
      confidence interval 1.12-1.42; p<0.001). Other predictive factors included
      cigarette smoking, alcohol and coffee drinking, and heating the home with a coal
      fire, with some evidence for iron and calcium intake having protective effects.
      CONCLUSION: The mean BLL in this group of pregnant women is higher than has been
      found in similar populations in developed countries. The finding that high
      education attainment was independently associated with higher BLL was unexpected
      and currently unexplained. Reduction in maternal lead levels can best be
      undertaken by reducing intake of the social drugs cigarettes, alcohol and
      caffeine, although further investigation of the effect of calcium on lead levels
      is needed.

PMID- 24039754
TI  - The impact of polymorphic variations in the 5p15, 6p12, 6p21 and 15q25 Loci on
      the risk and prognosis of portuguese patients with non-small cell lung cancer.
AB  - INTRODUCTION: Polymorphic variants in the 5p15, 6p12, 6p21, and 15q25 loci were
      demonstrated to potentially contribute to lung cancer carcinogenesis. Therefore,
      this study was performed to assess the role of those variants in non-small cell
      lung cancer (NSCLC) risk and prognosis in a Portuguese population. MATERIALS AND
      METHODS: Blood from patients with NSCLC was prospectively collected. To perform
      an association study, DNA from these patients and healthy controls were genotyped
      for a panel of 19 SNPs using a Sequenom(r) MassARRAY platform. Kaplan-Meier
      curves were used to assess the overall survival (OS) and progression-free
      survival (PFS). RESULTS: One hundred and forty-four patients with NSCLC were
      successfully consecutively genotyped for the 19 SNPs. One SNP was associated with
      NSCLC risk: rs9295740 G/A. Two SNPs were associated with non-squamous histology:
      rs3024994 (VEGF intron 2) T/C and rs401681 C/T. Three SNPs were associated with
      response rate: rs3025035 (VEGF intron 7) C/T, rs833061 (VEGF -460) C/T and
      rs9295740 G/A. One SNP demonstrated an influence on PFS: rs401681 C/T at 5p15, p
      = 0.021. Four SNPs demonstrated an influence on OS: rs2010963 (VEGF +405 G/C), p
      = 0.042; rs3025010 (VEGF intron 5 C/T), p = 0.047; rs401681 C/T at 5p15, p =
      0.046; and rs31489 C/A at 5p15, p = 0.029. CONCLUSIONS: Our study suggests that
      SNPs in the 6p12, 6p21, and 5p15 loci may serve as risk, predictive and
      prognostic NSCLC biomarkers. In the future, SNPs identified in the genomes of
      patients may improve NSCLC screening strategies and therapeutic management as
      well.

PMID- 24039755
TI  - Anti-cadherin-17 antibody modulates beta-catenin signaling and tumorigenicity of
      hepatocellular carcinoma.
AB  - Cadherin-17 (CDH17) is an oncofetal molecule associated with poor prognostic
      outcomes of hepatocellular carcinoma (HCC), for which the treatment options are
      very limited. The present study investigates the therapeutic potential of a
      monoclonal antibody (Lic5) that targets the CDH17 antigen in HCC. In vitro
      experiments showed Lic5 could markedly reduce CDH17 expression in a dose
      dependent manner, suppress beta-catenin signaling, and induce cleavages of
      apoptotic enzymes caspase-8 and -9 in HCC cells. Treatment of animals in
      subcutaneous HCC xenograft model similarly demonstrated significant tumor growth
      inhibition (TGI) using Lic5 antibody alone (5 mg/kg, i.p., t.i.w.; ca.60-65% TGI
      vs. vehicle at day 28), or in combination with conventional chemotherapy regimen
      (cisplatin 1 mg/kg; ca. 85-90% TGI). Strikingly, lung metastasis was markedly
      suppressed by Lic5 treatments. Immunohistochemical and western blot analyses of
      xenograft explants revealed inactivation of the Wnt pathway and suppression of
      Wnt signaling components in HCC tissues. Collectively, anti-CDH17 antibody
      promises as an effective biologic agent for treating malignant HCC. 

PMID- 24039756
TI  - SNP detection in mRNA in living cells using allele specific FRET probes.
AB  - Live mRNA detection allows real time monitoring of specific transcripts and
      genetic alterations. The main challenge of live genetic detection is overcoming
      the high background generated by unbound probes and reaching high level of
      specificity with minimal off target effects. The use of Fluorescence Resonance
      Energy Transfer (FRET) probes allows differentiation between bound and unbound
      probes thus decreasing background. Probe specificity can be optimized by
      adjusting the length and through use of chemical modifications that alter binding
      affinity. Herein, we report the use of two oligonucleotide FRET probe system to
      detect a single nucleotide polymorphism (SNP) in murine Hras mRNA, which is
      associated with malignant transformations. The FRET oligonucleotides were
      modified with phosphorothioate (PS) bonds, 2'OMe RNA and LNA residues to enhance
      nuclease stability and improve SNP discrimination. Our results show that a point
      mutation in Hras can be detected in endogenous RNA of living cells. As determined
      by an Acceptor Photobleaching method, FRET levels were higher in cells
      transfected with perfect match FRET probes whereas a single mismatch showed
      decreased FRET signal. This approach promotes in vivo molecular imaging methods
      and could further be applied in cancer diagnosis and theranostic strategies. 

PMID- 24039757
TI  - Phenotypes of myopathy-related beta-tropomyosin mutants in human and mouse tissue
      cultures.
AB  - Mutations in TPM2 result in a variety of myopathies characterised by variable
      clinical and morphological features. We used human and mouse cultured cells to
      study the effects of beta-TM mutants. The mutants induced a range of phenotypes
      in human myoblasts, which generally changed upon differentiation to myotubes.
      Human myotubes transfected with the E41K-beta-TM(EGFP) mutant showed perinuclear
      aggregates. The G53ins-beta-TM(EGFP) mutant tended to accumulate in myoblasts but
      was incorporated into filamentous structures of myotubes. The K49del-beta
      TM(EGFP) and E122K-beta-TM(EGFP) mutants induced the formation of rod-like
      structures in human cells. The N202K-beta-TM(EGFP) mutant failed to integrate
      into thin filaments and formed accumulations in myotubes. The accumulation of
      mutant beta-TM(EGFP) in the perinuclear and peripheral areas of the cells was the
      striking feature in C2C12. We demonstrated that human tissue culture is a
      suitable system for studying the early stages of altered myofibrilogenesis and
      morphological changes linked to myopathy-related beta-TM mutants. In addition,
      the histopathological phenotype associated with expression of the various mutant
      proteins depends on the cell type and varies with the maturation of the muscle
      cell. Further, the phenotype is a combinatorial effect of the specific amino acid
      change and the temporal expression of the mutant protein.

PMID- 24039758
TI  - Application of fluorescent monocytes for probing immune complexes on antigen
      microarrays.
AB  - Microarrayed antigens are used for identifying serum antibodies with given
      specificities and for generating binding profiles. Antibodies bind to these
      arrayed antigens forming immune complexes and are conventionally identified by
      secondary labelled antibodies.In the body immune complexes are identified by bone
      marrow derived phagocytic cells, such as monocytes. In our work we were looking
      into the possibility of replacing secondary antibodies with monocytoid cells for
      the generation of antibody profiles. Using the human monocytoid cell line U937,
      which expresses cell surface receptors for immune complex components, we show
      that cell adhesion is completely dependent on the interaction of IgG heavy chains
      and Fcgamma receptors, and this recognition is susceptible to differences between
      heavy chain structures and their glycosylation. We also report data on a possible
      application of this system in autoimmune diagnostics.Compared to secondary
      antibodies, fluorescent monocytesas biosensors are superior in reflecting
      biological functions of microarray-bound antibodies and represent an easy and
      robust alternative for profiling interactions between serum proteins and
      antigens. 

PMID- 24039759
TI  - Glycan elongation beyond the mucin associated Tn antigen protects tumor cells
      from immune-mediated killing.
AB  - Membrane bound mucins are up-regulated and aberrantly glycosylated during
      malignant transformation in many cancer cells. This results in a negatively
      charged glycoprotein coat which may protect cancer cells from immune
      surveillance. However, only limited data have so far demonstrated the critical
      steps in glycan elongation that make aberrantly glycosylated mucins affect the
      interaction between cancer cells and cytotoxic effector cells of the immune
      system. Tn (GalNAc-Ser/Thr), STn (NeuAcalpha2-6GalNAc-Ser/Thr), T (Galbeta1
      3GalNAc-Ser/Thr), and ST (NeuAcalpha2-6Galbeta1-3GalNAc-Ser/Thr) antigens are
      recognized as cancer associated truncated glycans, and are expressed in many
      adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the
      role of the cancer associated glycan truncations in immune-mediated killing we
      created glyco-engineered breast- and pancreatic cancer cells expressing only the
      shortest possible mucin-like glycans (Tn and STn). Glyco-engineering was
      performed by zinc finger nuclease (ZFN) knockout (KO) of the Core 1 enzyme
      chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc
      residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic
      cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated
      antibody-dependent cellular-cytotoxicity (ADCC) and cytotoxic T lymphocyte (CTL)
      mediated killing. In addition, we investigated the association between total cell
      surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an
      inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and
      CTL-mediated killing. Together, these data suggest that up-regulation of membrane
      bound mucins protects cells from immune mediated killing, and that particular
      glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can
      be important for fine tuning of the immune escape mechanisms in cancer cells. 

PMID- 24039760
TI  - Effects of light intensity and nitrogen starvation on glycerolipid,
      glycerophospholipid, and carotenoid composition in Dunaliella tertiolecta
      culture.
AB  - Time-course variation of lipid and carotenoid production under high light (300
      MUE/m2s) and nitrogen starvation conditions was determined in a Dunaliella
      tertiolecta strain. Nanoelectrospray (nanoESI) chip based direct infusion was
      used for lipid analysis and ultra-performance liquid chromatography (UPLC)
      coupled with a photodiode array (PDA) or atmospheric chemical ionization mass
      spectrometry (APCI-MS) was used for carotenoid analysis. A total of 29 lipids and
      7 carotenoids were detected. Alterations to diacylglyceryltrimethylhomoserine
      (DGTS) and digalactosyldiacylglycerol (DGDG) species were significant
      observations under stress conditions. Their role in relation to the regulation of
      photosynthesis under stress condition is discussed in this study. The total
      carotenoid content was decreased under stress conditions, while a-carotene was
      increased under nitrate-deficient cultivation. The highest productivity of
      carotenoid was attained under high light and nitrate sufficiency (HLNS)
      condition, which result from the highest level of biomass under HLNS. When stress
      was induced at stationary phase, the substantial changes to the lipid composition
      occurred, and the higher carotenoid content and productivity were exhibited. This
      is the first report to investigate the variation of lipids, including
      glycerolipid, glycerophospholipid, and carotenoid in D. tertiolecta in response
      to stress conditions using lipidomics tools.

PMID- 24039761
TI  - Integrative analysis of porcine microRNAome during skeletal muscle development.
AB  - Pig is an important agricultural animal for meat production and provides a
      valuable model for many human diseases. Functional studies have demonstrated that
      microRNAs (miRNAs) play critical roles in almost all aspects of skeletal muscle
      development and disease pathogenesis. To investigate the miRNAs involved in
      regulating different periods of skeletal muscle development, we herein performed
      a comprehensive research for porcine microRNAome (miRNAome) during 10 skeletal
      muscle developmental stages including 35, 49, 63, 77, 91 dpc (days post coitum)
      and 2, 28, 90, 120, 180 dpn (days postnatal) using Solexa sequencing technology.
      Our results extend the repertoire of pig miRNAome to 247 known miRNAs processed
      from 210 pre-miRNAs and 297 candidate novel miRNAs through comparison with known
      miRNAs in the miRBase. Expression analysis of the 15 most abundant miRNAs in
      every library indicated that functional miRNAome may be smaller and tend to be
      highly expressed. A series of muscle-related miRNAs summarized in our study
      present different patterns between myofibers formation phase and muscle
      maturation phase, providing valuable reference for investigation of functional
      miRNAs during skeletal muscle development. Analysis of temporal profiles of miRNA
      expression identifies 18 novel candidate myogenic miRNAs in pig, which might
      provide new insight into regulation mechanism mediated by miRNAs underlying
      muscle development. 

PMID- 24039762
TI  - Association of two variants in SMAD7 with the risk of congenital heart disease in
      the Han Chinese population.
AB  - SMAD7 is a general antagonist of TGF-beta signaling and has been found to be
      involved in cardiogenesis in mouse models, but its role in human congenital heart
      disease (CHD) has yet to be investigated. To examine if SMAD7 is associated with
      CHD, we conducted a case-control study in the Han Chinese population. Exon1 and
      exon4 of SMAD7, which encode the functional MH1 and MH2 domains, were directly
      sequenced in 1,201 sporadic CHD patients and 1,116 control individuals. A total
      of 18 sequence variations were identified. Two common variants rs3809922 and
      rs3809923 are located at exon4 of SMAD7, and were found in strong linkage
      disequilibrium with each other (r2 = 0.93). We analyzed the association of these
      two loci with CHD in 3 independent subgroup case-control studies, and found that
      in some subgroups, rs3809922 and rs3809923 were significantly associated with CHD
      through genetic model analysis. In the combined data set, TT genotype in
      rs3809922 significantly increased the risk of CHD compared with CC and CT, while
      GG genotype in rs3809923 significantly increased the risk of CHD compared with CC
      and CG, particularly in the recessive model. In addition, haplotype analyses
      showed that haplotype TG significantly increased the risk of CHD (P = 6.9*10-6);
      this finding supports the results from the analyses based on single locus.
      According to data from the 1000 Genomes Project, the frequencies of the two risk
      alleles varied greatly between populations worldwide, which indicate the
      identified associations might have a population difference. To our knowledge,
      this is the first report that genetic variants in SMAD7 influence susceptibility
      to CHD risk.

PMID- 24039763
TI  - Test-retest reliability of graph metrics in functional brain networks: a resting
      state fNIRS study.
AB  - Recent research has demonstrated the feasibility of combining functional near
      infrared spectroscopy (fNIRS) and graph theory approaches to explore the
      topological attributes of human brain networks. However, the test-retest (TRT)
      reliability of the application of graph metrics to these networks remains to be
      elucidated. Here, we used resting-state fNIRS and a graph-theoretical approach to
      systematically address TRT reliability as it applies to various features of human
      brain networks, including functional connectivity, global network metrics and
      regional nodal centrality metrics. Eighteen subjects participated in two resting
      state fNIRS scan sessions held ~20 min apart. Functional brain networks were
      constructed for each subject by computing temporal correlations on three types of
      hemoglobin concentration information (HbO, HbR, and HbT). This was followed by a
      graph-theoretical analysis, and then an intraclass correlation coefficient (ICC)
      was further applied to quantify the TRT reliability of each network metric. We
      observed that a large proportion of resting-state functional connections (~90%)
      exhibited good reliability (0.6< ICC <0.74). For global and nodal measures,
      reliability was generally threshold-sensitive and varied among both network
      metrics and hemoglobin concentration signals. Specifically, the majority of
      global metrics exhibited fair to excellent reliability, with notably higher ICC
      values for the clustering coefficient (HbO: 0.76; HbR: 0.78; HbT: 0.53) and
      global efficiency (HbO: 0.76; HbR: 0.70; HbT: 0.78). Similarly, both nodal degree
      and efficiency measures also showed fair to excellent reliability across nodes
      (degree: 0.52~0.84; efficiency: 0.50~0.84); reliability was concordant across
      HbO, HbR and HbT and was significantly higher than that of nodal betweenness
      (0.28~0.68). Together, our results suggest that most graph-theoretical network
      metrics derived from fNIRS are TRT reliable and can be used effectively for brain
      network research. This study also provides important guidance on the choice of
      network metrics of interest for future applied research in developmental and
      clinical neuroscience. 

PMID- 24039764
TI  - The ZIP5 ectodomain co-localizes with PrP and may acquire a PrP-like fold that
      assembles into a dimer.
AB  - The cellular prion protein (PrP(C)) was recently observed to co-purify with
      members of the LIV-1 subfamily of ZIP zinc transporters (LZTs), precipitating the
      surprising discovery that the prion gene family descended from an ancestral LZT
      gene. Here, we compared the subcellular distribution and biophysical
      characteristics of LZTs and their PrP-like ectodomains. When expressed in
      neuroblastoma cells, the ZIP5 member of the LZT subfamily was observed to be
      largely directed to the same subcellular locations as PrP(C) and both proteins
      were seen to be endocytosed through vesicles decorated with the Rab5 marker
      protein. When recombinantly expressed, the PrP-like domain of ZIP5 could be
      obtained with yields and levels of purity sufficient for structural analyses but
      it tended to aggregate, thereby precluding attempts to study its structure. These
      obstacles were overcome by moving to a mammalian cell expression system. The
      subsequent biophysical characterization of a homogeneous preparation of the ZIP5
      PrP-like ectodomain shows that this protein acquires a dimeric, largely globular
      fold with an alpha-helical content similar to that of mammalian PrP(C). The use
      of a mammalian cell expression system also allowed for the expression and
      purification of stable preparations of Takifugu rubripes PrP-1, thereby
      overcoming a key hindrance to high-resolution work on a fish PrP(C). 

PMID- 24039765
TI  - Phylodynamics of the HIV-1 epidemic in Cuba.
AB  - Previous studies have shown that the HIV-1 epidemic in Cuba displayed a complex
      molecular epidemiologic profile with circulation of several subtypes and
      circulating recombinant forms (CRF); but the evolutionary and population history
      of those viral variants remains unknown. HIV-1 pol sequences of the most
      prevalent Cuban lineages (subtypes B, C and G, CRF18_cpx, CRF19_cpx, and
      CRFs20/23/24_BG) isolated between 1999 and 2011 were analyzed. Maximum-likelihood
      analyses revealed multiple introductions of subtype B (n>=66), subtype C (n>=10),
      subtype G (n>=8) and CRF18_cpx (n>=2) viruses in Cuba. The bulk of HIV-1
      infections in this country, however, was caused by dissemination of a few founder
      strains probably introduced from North America/Europe (clades B(CU-I) and B(CU
      II)), east Africa (clade C(CU-I)) and central Africa (clades G(CU), CRF18(CU) and
      CRF19(CU)), or locally generated (clades CRFs20/23/24_BG). Bayesian-coalescent
      analyses show that the major HIV-1 founder strains were introduced into Cuba
      during 1985-1995; whereas the CRFs_BG strains emerged in the second half of the
      1990s. Most HIV-1 Cuban clades appear to have experienced an initial period of
      fast exponential spread during the 1990s and early 2000s, followed by a more
      recent decline in growth rate. The median initial growth rate of HIV-1 Cuban
      clades ranged from 0.4 year-1 to 1.6 year-1. Thus, the HIV-1 epidemic in Cuba has
      been a result of the successful introduction of a few viral strains that began to
      circulate at a rather late time of the AIDS pandemic, but then were rapidly
      disseminated through local transmission networks.

PMID- 24039766
TI  - Plasma sphingosine-1-phosphate is elevated in obesity.
AB  - BACKGROUND: Dysfunctional lipid metabolism is a hallmark of obesity and insulin
      resistance and a risk factor for various cardiovascular and metabolic
      complications. In addition to the well known increase in plasma triglycerides and
      free fatty acids, recent work in humans and rodents has shown that obesity is
      associated with elevations in the bioactive class of sphingolipids known as
      ceramides. However, in obesity little is known about the plasma concentrations of
      sphinogsine-1-phosphate (S1P), the breakdown product of ceramide, which is an
      important signaling molecule in mammalian biology. Therefore, the purpose of this
      study was to examine the impact of obesity on circulating S1P concentration and
      its relationship with markers of glucose metabolism and insulin sensitivity.
      METHODOLOGY/PRINCIPAL FINDINGS: Plasma S1P levels were determined in high-fat
      diet (HFD)-induced and genetically obese (ob/ob) mice along with obese humans.
      Circulating S1P was elevated in both obese mouse models and in obese humans
      compared with lean healthy controls. Furthermore, in humans, plasma S1P
      positively correlated with total body fat percentage, body mass index (BMI),
      waist circumference, fasting insulin, HOMA-IR, HbA1c (%), total and LDL
      cholesterol. In addition, fasting increased plasma S1P levels in lean healthy
      mice. CONCLUSION: We show that elevations in plasma S1P are a feature of both
      human and rodent obesity and correlate with metabolic abnormalities such as
      adiposity and insulin resistance.

PMID- 24039767
TI  - Neuroligin 2 is expressed in synapses established by cholinergic cells in the
      mouse brain.
AB  - Neuroligin 2 is a postsynaptic protein that plays a critical role in the
      maturation and proper function of GABAergic synapses. Previous studies
      demonstrated that deletion of neuroligin 2 impaired GABAergic synaptic
      transmission, whereas its overexpression caused increased inhibition, which
      suggest that its presence strongly influences synaptic function. Interestingly,
      the overexpressing transgenic mouse line showed increased anxiety-like behavior
      and other behavioral phenotypes, not easily explained by an otherwise
      strengthened GABAergic transmission. This suggested that other, non-GABAergic
      synapses may also express neuroligin 2. Here, we tested the presence of
      neuroligin 2 at synapses established by cholinergic neurons in the mouse brain
      using serial electron microscopic sections double labeled for neuroligin 2 and
      choline acetyltransferase. We found that besides GABAergic synapses, neuroligin 2
      is also present in the postsynaptic membrane of cholinergic synapses in all
      investigated brain areas (including dorsal hippocampus, somatosensory and medial
      prefrontal cortices, caudate putamen, basolateral amygdala, centrolateral
      thalamic nucleus, medial septum, vertical- and horizontal limbs of the diagonal
      band of Broca, substantia innominata and ventral pallidum). In the hippocampus,
      the density of neuroligin 2 labeling was similar in GABAergic and cholinergic
      synapses. Moreover, several cholinergic contact sites that were strongly labeled
      with neuroligin 2 did not resemble typical synapses, suggesting that cholinergic
      axons form more synaptic connections than it was recognized previously. We showed
      that cholinergic cells themselves also express neuroligin 2 in a subset of their
      input synapses. These data indicate that mutations in human neuroligin 2 gene and
      genetic manipulations of neuroligin 2 levels in rodents will potentially cause
      alterations in the cholinergic system as well, which may also have a profound
      effect on the functional properties of brain circuits and behavior. 

PMID- 24039768
TI  - Monoubiquitination of ancient ubiquitous protein 1 promotes lipid droplet
      clustering.
AB  - Lipid droplets, the intracellular storage organelles for neutral lipids, exist in
      a wide range of sizes and of morphologically distinct organization, from loosely
      dispersed lipid droplets to tightly packed lipid droplet clusters. We show that
      the lipid droplet protein AUP1 induces cluster formation. A fraction of AUP1 is
      monoubiquitinated at various lysine residues. This process depends on its
      internal CUE domain, which is a known ubiquitin-binding domain. AUP1 with a
      deleted or point mutagenized CUE domain, as well as a lysine-free mutant, are not
      ubiquitinated and do not induce lipid droplet clustering. When such
      ubiquitination deficient mutants are fused to ubiquitin, clustering is restored.
      AUP1 mutants with defective droplet targeting fail to induce clustering. Also,
      another lipid droplet protein, NSDHL, with a fused ubiquitin does not induce
      clustering. The data indicate that monoubiquitinated AUP1 on the lipid droplet
      surface specifically induces clustering, and suggest a homophilic interaction
      with a second AUP1 molecule or a heterophilic interaction with another ubiquitin
      binding protein. 

PMID- 24039769
TI  - A cell-permeable fusion protein based on Clostridium botulinum C2 toxin for
      delivery of p53 tumorsuppressor into cancer cells.
AB  - Genetically engineered bacterial protein toxins are attractive systems for
      delivery of exogenous proteins into the cytosol of mammalian cells. The binary C2
      toxin from C. botulinum has emerged as powerful delivery vehicle, which rests on
      its binding/translocation component C2IIa and the genetically modified adaptor
      domain C2IN that act in concert to trigger cell uptake. The p53 tumor suppressor
      protein has a crucial function in suppressing carcinogenesis and is frequently
      inactivated by diverse mechanisms in human tumor cells. Therefore, we constructed
      a C2IN-p53 fusion protein, which is internalized into cancer cells by C2IIa. To
      this end, the C2IN-p53 fusion construct was overexpressed in E. coli with good
      solubility, purified by heparin affinity chromatography and protein identity was
      confirmed by immunoblotting. We demonstrated that the fusion protein is capable
      of binding to the p53 consensus-DNA with high affinity in a p53-specific manner
      in vitro. Next, the internalization of C2IN-p53 was monitored in HeLa cells by
      cell fractionation and immunoblot analysis, which revealed a C2IIa-mediated
      translocation of the fusion protein into the cytosol. The uptake was also shown
      in A549 and Saos-2 cells with similar efficiency. These findings were further
      corroborated by confocal immunofluorescence analyses of C2IN-p53/C2IIa-treated
      HeLa and A549 cells, displaying predominantly cytoplasmic localization of the
      fusion construct. 

PMID- 24039770
TI  - Breaking of plant stomatal one-cell-spacing rule by sugar solution immersion.
AB  - The spatial distribution of plant stomata is a model system to study epidermal
      cell pattern formation. Molecular genetic approaches have identified several key
      genes required for stomatal distribution patterning, but environmental conditions
      that perturb the stomatal spacing distribution have not yet been identified. We
      found that immersing hydroponic cultures in 1-5% sucrose solution induced
      abnormally clustered stomata in the cotyledons of Arabidopsis seedlings.
      Clustered stomata were also induced by treatment with glucose or fructose
      solution but not by mannitol solution, suggesting that osmotic stress was not a
      cause of the disturbed stomatal patterns. Stomatal lineage cell-specific enhancer
      trap lines revealed that the sugar solution treatment led to ectopic expression
      of stomatal lineage cell-specific genes in non-stomatal lineage cells. Aniline
      blue staining also showed that there was reduced deposition of callose, a plant
      cell wall component, in new cell walls during formation of stomatal precursor
      cells (meristemoids). These results suggested that the immersion treatment with
      sugar solution permitted ectopic guard cell differentiation through dysfunction
      of the cell wall dividing stomatal- and non-stomatal lineage cells. Our simple
      induction system for clustered stomata provides a suitable tool for further
      studies to investigate the one-cell-spacing rule during plant stomatal
      development. 

PMID- 24039771
TI  - Direct quantification of mRNA and miRNA from cell lysates using reverse
      transcription real time PCR: a multidimensional analysis of the performance of
      reagents and workflows.
AB  - Substantial efforts have been devoted to in vitro testing of candidate
      chemotherapeutics by profiling transcriptional changes across the collection of
      NCI-60 cell-lines. A work-flow with reagents that enable the direct
      quantification of RNA of different molecular sizes simultaneously in the same
      sample without laborious total RNA isolation will invariably increase the
      throughput and accuracy of the study. MicroRNAs (miRNAs) are known to regulate
      most cellular functions, acting post-transcriptionally by repressing numerous
      eukaryotic mRNAs. Recent findings on the remarkable stability of miRNA prompted
      us to investigate the feasibility of quantifying the expression levels of both
      mRNA and miRNA directly from cell lysates (cell-to-Ct). Multidimensional analyses
      of the expressions of mRNA and miRNA across seven NCI-60 cell lines and multiple
      reagents were conducted to assess the performances of these reagents and
      workflows for cell-to-Ct measurements using reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR). Quantification of RNA species using lysates
      prepared from an in-house and one of the commercial reagents demonstrated
      comparable performance to those prepared by the more laborious and conventional
      method of using guanidinium-phenol-chloroform. Additionally, miRNA was found to
      be highly stable in the cell lysates when incubated at room temperature for
      prolonged period of time and subjected to multiple freeze-thaw cycles. In
      summary, this study demonstrated significant differences in pre-analytical
      performance of a variety of commercially available reagents and described a cost
      effective reagent useful for rapid, scalable, and high-throughput workflow for
      the detection of mRNA and miRNA from the same biological sample. 

PMID- 24039772
TI  - Development and validation of a questionnaire to detect behavior change in
      multiple advance care planning behaviors.
AB  - INTRODUCTION: Advance directives have traditionally been considered the gold
      standard for advance care planning. However, recent evidence suggests that
      advance care planning involves a series of multiple discrete behaviors for which
      people are in varying stages of behavior change. The goal of our study was to
      develop and validate a survey to measure the full advance care planning process.
      METHODS: The Advance Care Planning Engagement Survey assesses "Process Measures"
      of factors known from Behavior Change Theory to affect behavior (knowledge,
      contemplation, self-efficacy, and readiness, using 5-point Likert scales) and
      "Action Measures" (yes/no) of multiple behaviors related to surrogate decision
      makers, values and quality of life, flexibility for surrogate decision making,
      and informed decision making. We administered surveys at baseline and 1 week
      later to 50 diverse, older adults from San Francisco hospitals. Internal
      consistency reliability of Process Measures was assessed using Cronbach's alpha
      (only continuous variables) and test-retest reliability of Process and Action
      Measures was examined using intraclass correlations. For discriminant validity,
      we compared Process and Action Measure scores between this cohort and 20 healthy
      college students (mean age 23.2 years, SD 2.7). RESULTS: Mean age was 69.3 (SD
      10.5) and 42% were non-White. The survey took a mean of 21.4 minutes (+/-6.2) to
      administer. The survey had good internal consistency (Process Measures Cronbach's
      alpha, 0.94) and test-retest reliability (Process Measures intraclass
      correlation, 0.70; Action Measures, 0.87). Both Process and Action Measure scores
      were higher in the older than younger group, p<.001. CONCLUSION: A new Advance
      Care Planning Engagement Survey that measures behavior change (knowledge,
      contemplation, self-efficacy, and readiness) and multiple advance care planning
      actions demonstrates good reliability and validity. Further research is needed to
      assess whether survey scores improve in response to advance care planning
      interventions and whether scores are associated with receipt of care consistent
      with one's wishes.

PMID- 24039773
TI  - EGF-induced bronchial epithelial cells drive neutrophil chemotactic and anti
      apoptotic activity in asthma.
AB  - Chronic damage and repair of the bronchial epithelium are features of asthma. We
      have previously reported that ex vivo stimulation of normal bronchial epithelial
      cells with epidermal growth factor (EGF), a key factor of epithelial repair,
      enhances the mechanisms of neutrophil accumulation, thereby promoting neutrophil
      defences during acute injury but potentially enhancing inflammation in chronic
      airway diseases. We have now sought to (i) determine whether this EGF-dependent
      pro-neutrophil activity is increased in asthma, where EGF and its epithelial
      receptor are over-expressed, and (ii) elucidate some of the mechanisms underlying
      this asthmatic epithelial-neutrophil interaction. Primary bronchial epithelial
      cells (PBEC) from healthy subjects, mild asthmatics and moderate-to-severe
      asthmatics (Mod/Sev) were stimulated with EGF, a model that mimics a repairing
      epithelium. Conditioned culture media (EGF-CM) were assessed for neutrophil
      chemotactic and anti-apoptotic activities and inflammatory mediator production.
      EGF induced the epithelium to produce soluble mediators with neutrophil
      chemotactic (p<0.001) and pro-survival (p = 0.021) activities which were related
      to the clinical severity of asthma (trend p = 0.010 and p = 0.009, respectively).
      This was associated with enhanced IL-6, IL-8, GM-CSF and TNF-alpha release, and
      cytokine-neutralising experiments using EGF-CM from Mod/Sev asthmatics
      demonstrated a role for GM-CSF in neutrophil survival (p<0.001). Pre-treatment of
      neutrophils with specific inhibitors of the myeloid-restricted class I
      phosphatidylinositol-3-OH kinase (PI(3)K) isoforms showed that the EGF-CM from
      Mod/Sev asthmatics depended on the gamma (p<0.021) but not delta isoforms, while
      neutrophil survival required multiple class I PI(3)Ks. The EGF-induced
      chemotactic, but not pro-survival activity, involved RhoA signaling in
      neutrophils (p = 0.012). EGF whose activity is upregulated in asthma induces ex
      vivo the epithelium from asthmatic patients to produce pro-neutrophil activities;
      these are related to asthma severity and, in moderate-to-severe asthmatics,
      involves class IB PI(3)Kgamma signaling, providing a potential therapeutic target
      for neutrophilic forms of asthma. 

PMID- 24039774
TI  - Vaccination with conserved regions of erythrocyte-binding antigens induces
      neutralizing antibodies against multiple strains of Plasmodium falciparum.
AB  - BACKGROUND: A highly effective vaccine against Plasmodium falciparum malaria
      should induce potent, strain transcending immunity that broadly protects against
      the diverse population of parasites circulating globally. We aimed to identify
      vaccine candidates that fulfill the criteria. METHODS: We have measured growth
      inhibitory activity of antibodies raised to a range of antigens to identify those
      that can efficiently block merozoite invasion for geographically diverse strains
      of P. falciparum. RESULTS: This has shown that the conserved Region III-V, of the
      P. falciparum erythrocyte-binding antigen (EBA)-175 was able to induce antibodies
      that potently inhibit merozoite invasion across diverse parasite strains,
      including those reliant on invasion pathways independent of EBA-175 function.
      Additionally, the conserved RIII-V domain of EBA-140 also induced antibodies with
      strong in vitro parasite growth inhibitory activity. CONCLUSION: We identify an
      alternative, highly conserved region (RIV-V) of EBA-175, present in all EBA
      proteins, that is the target of potent, strain transcending neutralizing
      antibodies, that represents a strong candidate for development as a component in
      a malaria vaccine.

PMID- 24039775
TI  - Mannose-binding lectin inhibits monocyte proliferation through transforming
      growth factor-beta1 and p38 signaling pathways.
AB  - Mannose-binding lectin (MBL), a plasma C-type lectin, plays an important role in
      innate immunity. However, the interaction, and the consequences of it, between
      MBL and the immune system remain ill defined. We have investigated the
      contributing mechanisms and effects of MBL on the proliferation of human
      monocytes. At lower concentrations (<=4 MUg/ml) MBL was shown to partially
      enhance monocyte proliferation. By contrast, at higher concentrations (8-20
      MUg/ml) of MBL, cell proliferation was markedly attenuated. MBL-induced growth
      inhibition was associated with G0/G1 arrest, down-regulation of cyclin D1/D3,
      cyclin-dependent kinase (Cdk) 2/Cdk4 and up-regulation of the Cdk inhibitory
      protein Cip1/p21. Additionally, MBL induced apoptosis, and did so through caspase
      3 activation and poly ADP-ribose polymerase (PARP) cleavage. Moreover,
      transforming growth factor (TGF)-beta1 levels increased in the supernatants of
      MBL-stimulated monocyte cultures. We also found that MBL-dependent inhibition of
      monocyte proliferation could be reversed by the TGF-beta receptor antagonist SB
      431542, or by anti-TGF-beta1 antibody, or by the mitogen-activated protein kinase
      (MAPK) inhibitors specific for p38 (SB203580), but not ERK (U0126) or JNK
      (SP600125). Thus, at high concentrations, MBL can affect the immune system by
      inhibiting monocyte proliferation, which suggests that MBL may exhibit anti
      inflammatory effects. 

PMID- 24039776
TI  - Testing the ability of non-methylamine osmolytes present in kidney cells to
      counteract the deleterious effects of urea on structure, stability and function
      of proteins.
AB  - Human kidney cells are under constant urea stress due to its urine concentrating
      mechanism. It is believed that the deleterious effect of urea is counteracted by
      methylamine osmolytes (glycine betaine and glycerophosphocholine) present in
      kidney cells. A question arises: Do the stabilizing osmolytes, non-methylamines
      (myo-inositol, sorbitol and taurine) present in the kidney cells also counteract
      the deleterious effects of urea? To answer this question, we have measured
      structure, thermodynamic stability (DeltaG D (o)) and functional activity
      parameters (K m and k cat) of different model proteins in the presence of various
      concentrations of urea and each non-methylamine osmolyte alone and in
      combination. We observed that (i) for each protein myo-inositol provides perfect
      counteraction at 1?2 ([myo-inositol]:[urea]) ratio, (ii) any concentration of
      sorbitol fails to refold urea denatured proteins if it is six times less than
      that of urea, and (iii) taurine regulates perfect counteraction in a protein
      specific manner; 1.5?2.0, 1.2?2.0 and 1.0?2.0 ([taurine]:[urea]) ratios for RNase
      A, lysozyme and alpha-lactalbumin, respectively. 

PMID- 24039777
TI  - Micro-structural brain alterations in aviremic HIV+ patients with minor
      neurocognitive disorders: a multi-contrast study at high field.
AB  - OBJECTIVE: Mild neurocognitive disorders (MND) affect a subset of HIV+ patients
      under effective combination antiretroviral therapy (cART). In this study, we used
      an innovative multi-contrast magnetic resonance imaging (MRI) approach at high
      field to assess the presence of micro-structural brain alterations in MND+
      patients. METHODS: We enrolled 17 MND+ and 19 MND- patients with undetectable HIV
      1 RNA and 19 healthy controls (HC). MRI acquisitions at 3T included: MP2RAGE for
      T1 relaxation times, Magnetization Transfer (MT), T2* and Susceptibility Weighted
      Imaging (SWI) to probe micro-structural integrity and iron deposition in the
      brain. Statistical analysis used permutation-based tests and correction for
      family-wise error rate. Multiple regression analysis was performed between MRI
      data and (i) neuropsychological results (ii) HIV infection characteristics. A
      linear discriminant analysis (LDA) based on MRI data was performed between MND+
      and MND- patients and cross-validated with a leave-one-out test. RESULTS: Our
      data revealed loss of structural integrity and micro-oedema in MND+ compared to
      HC in the global white and cortical gray matter, as well as in the thalamus and
      basal ganglia. Multiple regression analysis showed a significant influence of sub
      cortical nuclei alterations on the executive index of MND+ patients (p = 0.04 he
      and R2 = 95.2). The LDA distinguished MND+ and MND- patients with a
      classification quality of 73% after cross-validation. CONCLUSION: Our study shows
      micro-structural brain tissue alterations in MND+ patients under effective
      therapy and suggests that multi-contrast MRI at high field is a powerful approach
      to discriminate between HIV+ patients on cART with and without mild
      neurocognitive deficits.

PMID- 24039778
TI  - Quercetin inhibits left ventricular hypertrophy in spontaneously hypertensive
      rats and inhibits angiotensin II-induced H9C2 cells hypertrophy by enhancing PPAR
      gamma expression and suppressing AP-1 activity.
AB  - BACKGROUND: Quercetin is the most abundant flavonoid in fruit and vegetables and
      is believed to attenuate cardiovascular disease. We hypothesized that quercetin
      inhibits cardiac hypertrophy by blocking AP-1 (c-fos, c-jun) and activating PPAR
      gamma signaling pathways. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study
      was to identify the mechanism underlying quercetin-mediated attenuation of
      cardiac hypertrophy. Quercetin therapy reduced blood pressure and markedly
      reduced the ratio of left ventricular to body weight (LVW/BW) (P<0.05, vs.
      spontaneously hypertensive rats (SHRs)). In vitro, quercetin also significantly
      attenuated Ang II-induced H9C2 cells hypertrophy, as indicated by its
      concentration dependent inhibitory effects on [3H]leucine incorporation into H9C2
      cells (64% reduction) and by the reduced hypertrophic surface area in H9C2 cells
      compared with the Ang II group (P<0.01, vs. Ang II group). Concurrently, we found
      that PPAR-gamma activity was significantly increased in the quercetin-treated
      group both in vivo and in vitro when analyzed using immunofluorescent or
      immunohistochemical assays (P<0.05, vs. SHRs or P<0.01, vs. the Ang II group).
      Conversely, in vivo, AP-1 (c-fos, s-jun) activation was suppressed in the
      quercetin-treated group, as was the downstream hypertrophy gene, including mRNA
      levels of ANP and BNP (P<0.05, vs. SHRs). Additionally, both western blotting and
      real time-PCR demonstrated that PPAR-gamma protein and mRNA were increased in the
      myocardium and AP-1 protein and mRNA were significantly decreased in the
      quercetin-treated group (P<0.05, vs. SHRs). Furthermore, western blotting and
      real time-PCR analyses also showed that transfection with PPAR-gamma siRNA
      significantly increased AP-1 signaling and reversed the effects of quercetin
      inhibition on mRNA expression levels of genes such as ANP and BNP in hypertrophic
      H9C2 cells. CONCLUSIONS: Our data indicate that quercetin may inhibit cardiac
      hypertrophy by enhancing PPAR-gamma expression and by suppressing the AP-1
      signaling pathway.

PMID- 24039779
TI  - Lutein protects against methotrexate-induced and reactive oxygen species-mediated
      apoptotic cell injury of IEC-6 cells.
AB  - PURPOSE: High-dose chemotherapy using methotrexate (MTX) frequently induces side
      effects such as mucositis that leads to intestinal damage and diarrhea. Several
      natural compounds have been demonstrated of their effectiveness in protecting
      intestinal epithelial cells from these adverse effects. In this paper, we
      investigated the protection mechanism of lutein against MTX-induced damage in IEC
      6 cells originating from the rat jejunum crypt. METHODS: The cell viability,
      induced-apoptosis, reactive oxygen species (ROS) generation, and mitochondrial
      membrane potential in IEC-6 cells under MTX treatment were examined in the
      presence or absence of lutein. Expression level of Bcl2, Bad and ROS scavenging
      enzymes (including SOD, catalase and Prdx1) were detected by quantitative RT-PCR.
      RESULTS: The cell viability of IEC-6 cells exposed to MTX was decreased in a dose
      and time-dependent manner. MTX induces mitochondrial membrane potential loss,
      ROS generation and caspase 3 activation in IEC-6 cells. The cytotoxicity of MTX
      was reduced in IEC-6 cells by the 24 h pre-treatment of lutein. We found that pre
      treatment of lutein significantly reduces MTX-induced ROS and apoptosis. The
      expression of SOD was up-regulated by the pre-treatment of lutein in the MTX
      treated IEC-6 cells. These results indicated that lutein can protect IEC-6 cells
      from the chemo-drugs induced damage through increasing ROS scavenging ability.
      CONCLUSION: The MTX-induced apoptosis of IEC-6 cells was shown to be repressed by
      the pre-treatment of lutein, which may represent a promising adjunct to
      conventional chemotherapy for preventing intestinal damages.

PMID- 24039780
TI  - Operational implementation of LED fluorescence microscopy in screening
      tuberculosis suspects in an urban HIV clinic in Uganda.
AB  - BACKGROUND: Light emitting diode (LED) fluorescence microscopy (FM) is an
      affordable, technology targeted for use in resource-limited settings and
      recommended for widespread roll-out by the World Health Organization (WHO). We
      sought to compare the operational performance of three LED FM methods compared to
      light microscopy in a cohort of HIV-positive tuberculosis (TB) suspects at an
      urban clinic in a high TB burden country. METHODS: Two spot specimens collected
      from TB suspects were included in the study. Smears were stained using auramine O
      method and read after blinding by three LED-based FM methods by trained
      laboratory technicians in the Infectious Diseases Institutelaboratory. Leftover
      portions of the refrigerated sputum specimens were transported to the FIND
      Tuberculosis Research Laboratory for Ziehl Neelsen (ZN) smear preparation and
      reading by experienced technologist as well as liquid and solid culture. RESULTS:
      174 of 627 (27.8%) specimens collected yielded one or more positive mycobacterial
      cultures. 94.3% (164/174) were M. tuberculosis complex. LED FM was between 7.3
      11.0% more sensitive compared to ZN microscopy. Of the 592 specimens examined by
      all microscopy methods, there was no significant difference in sensitivity
      between the three LED FM methods. The specificity of the LED FM methods was
      between 6.1% and 7.7% lower than ZN microscopy (P<0.001), although exclusion of
      the single poor reader resulted in over 98% specificity for all FM methods.
      CONCLUSIONS: Laboratory technicians in routine settings can be trained to use FM
      which is more sensitive than ZN microscopy. Despite rigorous proficiency testing,
      there were operator-dependent accuracy issues which highlight the critical need
      for intensive quality assurance procedures during LED FM implementation. The low
      sensitivity of FM for HIV-positive individuals particularly those with low CD4 T
      cell counts, will limit the number of additional patients found by LED FM in
      countries with high rates of HIV co-infection.

PMID- 24039781
TI  - Effects of speaker emotional facial expression and listener age on incremental
      sentence processing.
AB  - We report two visual-world eye-tracking experiments that investigated how and
      with which time course emotional information from a speaker's face affects
      younger (N = 32, Mean age  = 23) and older (N = 32, Mean age  = 64) listeners'
      visual attention and language comprehension as they processed emotional sentences
      in a visual context. The age manipulation tested predictions by socio-emotional
      selectivity theory of a positivity effect in older adults. After viewing the
      emotional face of a speaker (happy or sad) on a computer display, participants
      were presented simultaneously with two pictures depicting opposite-valence events
      (positive and negative; IAPS database) while they listened to a sentence
      referring to one of the events. Participants' eye fixations on the pictures while
      processing the sentence were increased when the speaker's face was (vs. wasn't)
      emotionally congruent with the sentence. The enhancement occurred from the early
      stages of referential disambiguation and was modulated by age. For the older
      adults it was more pronounced with positive faces, and for the younger ones with
      negative faces. These findings demonstrate for the first time that emotional
      facial expressions, similarly to previously-studied speaker cues such as eye gaze
      and gestures, are rapidly integrated into sentence processing. They also provide
      new evidence for positivity effects in older adults during situated sentence
      processing. 

PMID- 24039782
TI  - Targeting gastrin-releasing peptide suppresses neuroblastoma progression via
      upregulation of PTEN signaling.
AB  - We have previously demonstrated the role of gastrin-releasing peptide (GRP) as an
      autocrine growth factor for neuroblastoma. Here, we report that GRP silencing
      regulates cell signaling involved in the invasion-metastasis cascade. Using a
      doxycycline inducible system, we demonstrate that GRP silencing decreased
      anchorage-independent growth, inhibited migration and neuroblastoma cell-mediated
      angiogenesis in vitro, and suppressed metastasis in vivo. Targeted inhibition of
      GRP decreased the mRNA levels of oncogenes responsible for neuroblastoma
      progression. We also identified PTEN/AKT signaling as a key mediator of the
      tumorigenic properties of GRP in neuroblastoma cells. Interestingly, PTEN
      overexpression decreased GRP-mediated migration and angiogenesis; a novel role
      for this, otherwise, understated tumor suppressor in neuroblastoma. Furthermore,
      activation of AKT (pAKT) positively correlated with neuroblastoma progression in
      an in vivo tumor-metastasis model. PTEN expression was slightly decreased in
      metastatic lesions. A similar phenomenon was observed in human neuroblastoma
      sections, where, early-stage localized tumors had a higher PTEN expression
      relative to pAKT; however, an inverse expression pattern was observed in liver
      lesions. Taken together, our results argue for a dual purpose of targeting GRP in
      neuroblastoma--1) decreasing expression of critical oncogenes involved in tumor
      progression, and 2) enhancing activation of tumor suppressor genes to treat
      aggressive, advanced-stage disease.

PMID- 24039783
TI  - Comparative toxicities and synergism of apple orchard pesticides to Apis
      mellifera (L.) and Osmia cornifrons (Radoszkowski).
AB  - The topical toxicities of five commercial grade pesticides commonly sprayed in
      apple orchards were estimated on adult worker honey bees, Apis mellifera (L.)
      (Hymenoptera: Apidae) and Japanese orchard bees, Osmia cornifrons (Radoszkowski)
      (Hymenoptera: Megachilidae). The pesticides were acetamiprid (Assail 30SG),
      lambda-cyhalothrin (Warrior II), dimethoate (Dimethoate 4EC), phosmet (Imidan
      70W), and imidacloprid (Provado 1.6F). At least 5 doses of each chemical, diluted
      in distilled water, were applied to freshly-eclosed adult bees. Mortality was
      assessed after 48 hr. Dose-mortality regressions were analyzed by probit analysis
      to test the hypotheses of parallelism and equality by likelihood ratio tests. For
      A. mellifera, the decreasing order of toxicity at LD50 was imidacloprid, lambda
      cyhalothrin, dimethoate, phosmet, and acetamiprid. For O. cornifrons, the
      decreasing order of toxicity at LD50 was dimethoate, lambda-cyhalothrin,
      imidacloprid, acetamiprid, and phosmet. Interaction of imidacloprid or
      acetamiprid with the fungicide fenbuconazole (Indar 2F) was also tested in a 1?1
      proportion for each species. Estimates of response parameters for each mixture
      component applied to each species were compared with dose-response data for each
      mixture in statistical tests of the hypothesis of independent joint action. For
      each mixture, the interaction of fenbuconazole (a material non-toxic to both
      species) was significant and positive along the entire line for the pesticide.
      Our results clearly show that responses of A. mellifera cannot be extrapolated to
      responses of O.cornifrons, and that synergism of neonicotinoid insecticides and
      fungicides occurs using formulated product in mixtures as they are commonly
      applied in apple orchards.

PMID- 24039784
TI  - Protein kinase C beta mediates CD40 ligand-induced adhesion of monocytes to
      endothelial cells.
AB  - Accumulating evidence supports the early involvement of monocyte/macrophage
      recruitment to activated endothelial cells by leukocyte adhesion molecules during
      atherogenesis. CD40 and its ligand CD40L are highly expressed in vascular
      endothelial cells, but its impact on monocyte adhesion and the related molecular
      mechanisms are not fully understood. The present study was designed to evaluate
      the direct effect of CD40L on monocytic cell adhesion and gain mechanistic
      insight into the signaling coupling CD40L function to the proinflammatory
      response. Exposure of cultured human aortic endothelial cells (HAECs) to
      clinically relevant concentrations of CD40L (20 to 80 ng/mL) dose-dependently
      increased human monocytic THP-1 cells to adhere to them under static condition.
      CD40L treatment induced the expression of vascular cell adhesion molecule-1 (VCAM
      1) mRNA and protein expression in HAECs. Furthermore, exposure of HAECs to CD40L
      robustly increased the activation of protein kinase C beta (PKCbeta) in ECs. A
      selective inhibitor of PKCbeta prevented the rise in VCAM-1 and THP-1 cell
      adhesion to ECs. Moreover, stimulation of ECs to CD40L induced nuclear factor
      kappaB (NF-kappaB) activation. PKCbeta inhibition abolished CD40L-induced NF
      kappaB activation, and NF-kappaB inhibition reduced expression of VCAM-1, each
      resulting in reduced THP-1 cell adhesion. Our findings provide the evidence that
      CD40L increases VCAM-1 expression in ECs by activating PKCbeta and NF-kappaB,
      suggesting a novel mechanism for EC activation. Finally, administration of CD40L
      resulted in PKCbeta activation, increased VCAM-1 expression and activated
      monocytes adhesiveness to HAECs, processes attenuated by PKCbeta inhibitor.
      Therefore, CD40L may contribute directly to atherogenesis by activating ECs and
      recruiting monocytes to them. 

PMID- 24039785
TI  - Pituitary adenylate cyclase activating peptide (PACAP) participates in
      adipogenesis by activating ERK signaling pathway.
AB  - Pituitary adenylate cyclase activating peptide (PACAP) belongs to the
      secretin/glucagon/vasoactive intestinal peptide (VIP) family. Its action can be
      mediated by three different receptor subtypes: PAC1, which has exclusive affinity
      for PACAP, and VPAC1 and VPAC2 which have equal affinity for PACAP and VIP. We
      showed that all three receptors are expressed in 3T3-L1 cells throughout their
      differentiation into adipocytes. We established the activity of these receptors
      by cAMP accumulation upon induction by PACAP. Together with insulin and
      dexamethasone, PACAP induced adipogenesis in 3T3-L1 cell line. PACAP increased
      cAMP production within 15 min upon stimulation and targeted the expression and
      phosphorylation of MAPK (ERK1/2), strengthened by the ERK1/2 phosphorylation
      being partially or completely abolished by different combinations of PACAP
      receptors antagonists. We therefore speculate that ERK1/2 activation is crucial
      for the activation of CCAAT/enhancer- binding protein beta (C/EBPbeta). 

PMID- 24039786
TI  - Is the HIV epidemic stable among MSM in Mexico? HIV prevalence and risk behavior
      results from a nationally representative survey among men who have sex with men.
AB  - BACKGROUND: Recent evidence points to the apparent increase of HIV prevalence
      among men who have sex with men (MSM) in different settings with concentrated
      epidemics, including the Latin American region. In 2011, Mexico implemented an
      ambitious HIV prevention program in all major cities, funded by the Global Fund
      to Fight Aids, Tuberculosis and Malaria. The program was intended to strengthen
      the prevention response for the most at risk populations: MSM and injecting drug
      users. This paper presents the HIV prevalence results of a nationally
      representative baseline survey in 24 Mexican cities throughout the 5 regions in
      the country and reports the socio-demographic and sexual risk behaviors that
      predict the probability of infection. METHODS: The survey was implemented in two
      phases. We first identified and characterized places where MSM gather in each
      city and then conducted in a second phase, a seroprevalence survey that included
      rapid HIV testing and a self-administered questionnaire. The prevalence of HIV
      was estimated by adjusting for positive predicted value. We applied a probit
      model to estimate the probability of having a positive result from the HIV test
      as a function of socio-demographic characteristics and self-reported sexual risk
      behaviors. RESULTS: We found an overall HIV prevalence among MSM gathering in
      meeting points of 16.9% [95% CI: 15.6-18.3], significantly higher than previously
      reported estimates. Our regression results suggest that the risk of infection
      increases with age, with the number of sexual partners, and among those who play
      a receptive sexual role, and the risk decreases with higher education.
      DISCUSSION: Our findings suggest a higher HIV prevalence among MSM than
      previously acknowledged and that a significant regional variability exist
      throughout the country. These two findings combined, signal an important dynamic
      in the epidemic that should be better understood and promptly addressed with
      strong prevention efforts targeted at key populations.

PMID- 24039787
TI  - Epimorphin-induced MET sensitizes ovarian cancer cells to platinum.
AB  - Distinctive genotypic and phenotypic features of ovarian cancer via epithelial
      mesenchymal transition (EMT) have been correlated with drug resistance and
      disease recurrence. We investigated whether therapeutic reversal of EMT could re
      sensitize ovarian cancer cells (OCCs) to existing chemotherapy. We report that
      epimorphin, a morphogenic protein, has pivotal control over mesenchymal versus
      epithelial cell lineage decision of the putative OCCs. Exposure to epimorphin
      induced morphological changes reminiscent of mesenchymal-to-epithelial transition
      (MET), but in a dose dependent manner, i.e., at 10 ug/mL of epimorphin cells
      obtain a more mesenchymal-like morphology while at 20 ug/mL of epimorphin cells
      display an epithelial morphology. The latter changes were accompanied by
      suppression of mesenchymal markers, such as vimentin (~8-fold?, p<0.02), Twist1
      (~7-fold?, p<0.03), dystroglycan (~4-fold?, p<0.01) and palladin (~3-fold?,
      p<0.01). Conversely, significant elevations of KLF4 (~28-fold?, p<0.002), beta
      catenin (~6-fold?, p<0.004), EpCAM (~6-fold?, p<0.0002) and occludin (~15-fold?,
      p<0.004) mRNAs as part of the commitment to the epithelial cell lineage were
      detected in response to 20 ug/mL of exogenous epimorphin. Changes in occludin
      mRNA levels were accompanied by a parallel, albeit weaker expression at the
      protein level (~5-fold?, p<0.001). Likewise, acquisition of epithelial-like
      properties, including mucin1, CK19, and beta-catenin gene expression, was also
      obtained following epimorphin treatment. Further, MMP3 production was found to be
      reduced whereas laminin secretion was strongly amplified upon epimorphin-induced
      MET. These results suggest there is a dosage window for actions of epimorphin on
      cellular differentiation, wherein it can either suppress or enhance epithelial
      differentiation of OCCs. Importantly, induction of epithelial-like phenotypes by
      epimorphin led to an enhanced sensitivity to carboplatin. Overall, we demonstrate
      that epimorphin can revert OCCs away from their mesenchymal phenotype and toward
      an epithelial phenotype, thereby enhancing their sensitivity to a front-line
      chemotherapeutic agent. 

PMID- 24039788
TI  - Atrial remodeling is directly related to end-diastolic left ventricular pressure
      in a mouse model of ventricular pressure overload.
AB  - BACKGROUND: Atrial fibrillation (AF) is often preceded by underlying cardiac
      diseases causing ventricular pressure overload. OBJECTIVE: It was our aim to
      investigate the progression of atrial remodeling in a small animal model of
      ventricular pressure overload and its association with induction of AF. METHODS:
      Male mice were subjected to transverse aortic constriction (TAC) or sham
      operation. After four or eight weeks, echocardiographic measurements and
      hemodynamic measurements were made and AF induction was tested. The hearts were
      either fixed in formalin or ventricles and atria were separated, weighed and snap
      frozen for RNA analysis. RESULTS: Four weeks of pressure overload induced
      ventricular hypertrophy and minor changes in the atria. After eight weeks a
      significant reduction in left ventricular function occurred, associated with
      significant atrial remodeling including increased atrial weight, a trend towards
      an increased left atrial cell diameter, atrial dilatation and increased
      expression of markers of hypertrophy and inflammation. Histologically, no
      fibrosis was found in the left atrium. But atrial gene expression related to
      fibrosis was increased. Minor changes related to electrical remodeling were
      observed. AF inducibility was not different between the groups. Left ventricular
      end diastolic pressures were increased and correlated with the severity of atrial
      remodeling but not with AF induction. CONCLUSION: Permanent ventricular pressure
      overload by TAC induced atrial remodeling, including hypertrophy, dilatation and
      inflammation. The extent of atrial remodeling was directly related to LVEDP and
      not duration of TAC per se.

PMID- 24039789
TI  - SSVEP response is related to functional brain network topology entrained by the
      flickering stimulus.
AB  - Previous studies have shown that the brain network topology correlates with the
      cognitive function. However, few studies have investigated the relationship
      between functional brain networks that process sensory inputs and outputs. In
      this study, we focus on steady-state paradigms using a periodic visual stimulus,
      which are increasingly being used in both brain-computer interface (BCI) and
      cognitive neuroscience researches. Using the graph theoretical analysis, we
      investigated the relationship between the topology of functional networks
      entrained by periodic stimuli and steady state visually evoked potentials (SSVEP)
      using two frequencies and eleven subjects. First, the entire functional network
      (Network 0) of each frequency for each subject was constructed according to the
      coherence between electrode pairs. Next, Network 0 was divided into three sub
      networks, in which the connection strengths were either significantly (positively
      for Network 1, negatively for Network 3) or non-significantly (Network 2)
      correlated with the SSVEP responses. Our results revealed that the SSVEP
      responses were positively correlated to the mean functional connectivity,
      clustering coefficient, and global and local efficiencies, while these responses
      were negatively correlated with the characteristic path length of Networks 0, 1
      and 2. Furthermore, the strengths of these connections that significantly
      correlated with the SSVEP (both positively and negatively) were mainly found to
      be long-range connections between the parietal-occipital and frontal regions.
      These results indicate that larger SSVEP responses correspond with better
      functional network topology structures. This study may provide new insights for
      understanding brain mechanisms when using SSVEPs as frequency tags. 

PMID- 24039790
TI  - Sperm dynamics in spiders (Araneae): ultrastructural analysis of the sperm
      activation process in the garden spider Argiope bruennichi (Scopoli, 1772).
AB  - Storage of sperm inside the female genital tract is an integral phase of
      reproduction in many animal species. The sperm storage site constitutes the arena
      for sperm activation, sperm competition and female sperm choice. Consequently, to
      understand animal mating systems information on the processes that occur from
      sperm transfer to fertilization is required. Here, we focus on sperm activation
      in spiders. Male spiders produce sperm whose cell components are coiled within
      the sperm cell and that are surrounded by a proteinaceous sheath. These inactive
      and encapsulated sperm are transferred to the female spermathecae where they are
      stored for later fertilization. We analyzed the ultrastructural changes of sperm
      cells during residency time in the female genital system of the orb-web spider
      Argiope bruennichi. We found three clearly distinguishable sperm conditions:
      encapsulated sperm (secretion sheath present), decapsulated (secretion sheath
      absent) and uncoiled sperm (cell components uncoiled, presumably activated).
      After insemination, sperm remain in the encapsulated condition for several days
      and become decapsulated after variable periods of time. A variable portion of the
      decapsulated sperm transforms rapidly to the uncoiled condition resulting in a
      simultaneous occurrence of decapsulated and uncoiled sperm. After oviposition,
      only decapsulated and uncoiled sperm are left in the spermathecae, strongly
      suggesting that the activation process is not reversible. Furthermore, we found
      four different types of secretion in the spermathecae which might play a role in
      the decapsulation and activation process. 

PMID- 24039791
TI  - The influence of childhood aerobic fitness on learning and memory.
AB  - INTRODUCTION: There is a growing trend of inactivity among children, which may
      not only result in poorer physical health, but also poorer cognitive health.
      Previous research has shown that lower fitness has been related to decreased
      cognitive function for tasks requiring perception, memory, and cognitive control
      as well as lower academic achievement. PURPOSE: To investigate the relationship
      between aerobic fitness, learning, and memory on a task that involved remembering
      names and locations on a fictitious map. Different learning strategies and recall
      procedures were employed to better understand fitness effects on learning novel
      material. METHODS: Forty-eight 9-10 year old children (n = 24 high fit; HF and n
      = 24 low fit; LF) performed a task requiring them to learn the names of specific
      regions on a map, under two learning conditions in which they only studied (SO)
      versus a condition in which they were tested during study (TS). The retention day
      occurred one day after initial learning and involved two different recall
      conditions: free recall and cued recall. RESULTS: There were no differences in
      performance at initial learning between higher fit and lower fit participants.
      However, during the retention session higher fit children outperformed lower fit
      children, particularly when the initial learning strategy involved relatively
      poor recall performance (i.e., study only versus test-study strategy).
      CONCLUSIONS: We interpret these novel data to suggest that fitness can boost
      learning and memory of children and that these fitness-associated performance
      benefits are largest in conditions in which initial learning is the most
      challenging. Such data have important implications for both educational practice
      and policy.

PMID- 24039792
TI  - Congenital heart block maternal sera autoantibodies target an extracellular
      epitope on the alpha1G T-type calcium channel in human fetal hearts.
AB  - BACKGROUND: Congenital heart block (CHB) is a transplacentally acquired
      autoimmune disease associated with anti-Ro/SSA and anti-La/SSB maternal
      autoantibodies and is characterized primarily by atrioventricular (AV) block of
      the fetal heart. This study aims to investigate whether the T-type calcium
      channel subunit alpha1G may be a fetal target of maternal sera autoantibodies in
      CHB. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate differential mRNA expression
      of the T-type calcium channel CACNA1G (alpha1G gene) in the AV junction of human
      fetal hearts compared to the apex (18-22.6 weeks gestation). Using human fetal
      hearts (20-22 wks gestation), our immunoprecipitation (IP), Western blot analysis
      and immunofluorescence (IF) staining results, taken together, demonstrate
      accessibility of the alpha1G epitope on the surfaces of cardiomyocytes as well as
      reactivity of maternal serum from CHB affected pregnancies to the alpha1G
      protein. By ELISA we demonstrated maternal sera reactivity to alpha1G was
      significantly higher in CHB maternal sera compared to controls, and reactivity
      was epitope mapped to a peptide designated as p305 (corresponding to aa305-319 of
      the extracellular loop linking transmembrane segments S5-S6 in alpha1G repeat I).
      Maternal sera from CHB affected pregnancies also reacted more weakly to the
      homologous region (7/15 amino acids conserved) of the alpha1H channel.
      Electrophysiology experiments with single-cell patch-clamp also demonstrated
      effects of CHB maternal sera on T-type current in mouse sinoatrial node (SAN)
      cells. CONCLUSIONS/SIGNIFICANCE: Taken together, these results indicate that CHB
      maternal sera antibodies readily target an extracellular epitope of alpha1G T
      type calcium channels in human fetal cardiomyocytes. CHB maternal sera also show
      reactivity for alpha1H suggesting that autoantibodies can target multiple fetal
      targets.

PMID- 24039793
TI  - High correlation of the response of upper and lower lobe small airway epithelium
      to smoking.
AB  - The distribution of lung disease induced by inhaled cigarette smoke is complex,
      depending on many factors. With the knowledge that the small airway epithelium
      (SAE) is the earliest site of smoking-induced lung disease, and that the SAE gene
      expression is likely sensitive to inhaled cigarette smoke, we compared upper vs.
      lower lobe gene expression in the SAE within the same cigarette smokers to
      determine if the gene expression patterns were similar or different. Active
      smokers (n = 11) with early evidence of smoking-induced lung disease (normal
      spirometry but low diffusing capacity) underwent bronchoscopy and brushing of the
      upper and lower lobe SAE in order to compare upper vs lower lobe genome-wide and
      smoking-responsive gene expression by microarray. Cluster and principal component
      analysis demonstrated that, for each individual, the expression of the known SAE
      smoking-responsive genes were highly correlated in upper and lower lobe pairs,
      although, as expected, there were differences in the smoking-induced changes in
      gene expression from individual to individual. These observations support the
      concept that the heterogeneity observed among smokers in the anatomic
      distribution of smoking-induced disease are not secondary to the topographic
      differences in the effects of cigarette smoke on the airway epithelium. 

PMID- 24039794
TI  - Why did most French GPs choose not to join the voluntary national pay-for
      performance program?
AB  - BACKGROUND: In 2009, a voluntary pay for performance (P4P) scheme for primary
      care physicians was introduced in France through the 'Contract for Improving
      Individual Practice' (CAPI). Although the contract could be interrupted at any
      time and without any penalty, two-thirds of French general practitioners chose
      not to participate. We studied what factors motivated general practitioners not
      to subscribe to the P4P contract, and particularly their perception of the
      ethical risks that may be associated with adhering to a CAPI. METHOD: A cross
      sectional survey among French general practitioners using an online questionnaire
      based on focus group discussion results. Descriptive and multivariate statistical
      analyses with logistic regression. RESULTS: A sample of 1,016 respondents,
      representative of French GPs. The variables that were associated with the
      probability of not signing a CAPI were "discomfort that patients were not
      informed of the signing of a P4P contract by their doctors" (OR = 8.24, 95% CI =
      4.61-14.71), "the risk of conflicts of interest" (OR = 4.50, 95% CI = 2.42-8.35),
      "perceptions by patients that doctors may risk breaching professional ethics" (OR
      = 4. 35, 95% CI = 2.43-7.80) and "the risk of excluding the poorest patients" (OR
      = 2.66, 95% CI = 1.53-4.63). CONCLUSION: The perception of ethical risks
      associated with P4P may have hampered its success. Although the CAPI was extended
      to all GPs in 2012, our results question the relevance of the program itself by
      shedding light on potential adverse effects.

PMID- 24039795
TI  - Antiplatelets versus anticoagulants for the treatment of cervical artery
      dissection: Bayesian meta-analysis.
AB  - OBJECTIVE: To compare the effects of antiplatelets and anticoagulants on stroke
      and death in patients with acute cervical artery dissection. DESIGN: Systematic
      review with Bayesian meta-analysis. DATA SOURCES: The reviewers searched MEDLINE
      and EMBASE from inception to November 2012, checked reference lists, and
      contacted authors. STUDY SELECTION: Studies were eligible if they were
      randomised, quasi-randomised or observational comparisons of antiplatelets and
      anticoagulants in patients with cervical artery dissection. DATA EXTRACTION: Data
      were extracted by one reviewer and checked by another. Bayesian techniques were
      used to appropriately account for studies with scarce event data and imbalances
      in the size of comparison groups. DATA SYNTHESIS: Thirty-seven studies (1991
      patients) were included. We found no randomised trial. The primary analysis
      revealed a large treatment effect in favour of antiplatelets for preventing the
      primary composite outcome of ischaemic stroke, intracranial haemorrhage or death
      within the first 3 months after treatment initiation (relative risk 0.32, 95%
      credibility interval 0.12 to 0.63), while the degree of between-study
      heterogeneity was moderate (tau(2) = 0.18). In an analysis restricted to studies
      of higher methodological quality, the possible advantage of antiplatelets over
      anticoagulants was less obvious than in the main analysis (relative risk 0.73,
      95% credibility interval 0.17 to 2.30). CONCLUSION: In view of these results and
      the safety advantages, easier usage and lower cost of antiplatelets, we conclude
      that antiplatelets should be given precedence over anticoagulants as a first line
      treatment in patients with cervical artery dissection unless results of an
      adequately powered randomised trial suggest the opposite.

PMID- 24039796
TI  - Structural and functional implication of RAP80 DeltaGlu81 mutation.
AB  - Receptor Associated Protein 80 (RAP80) is a member of RAP80-BRCA1-CCDC98 complex
      family and helps in its recruitment to the DNA damage site for effective
      homologous recombination repair. It encompasses two tandem UIMs (UIM1 and UIM2)
      motif at its N-terminus, which interact with K-63 linked polyubiquitin chain(s)
      on H2AX and thereby assemble the RAP80-BRCA1 complex at the damage site.
      Nevertheless, how RAP80 helps in the structural integrity of BRCA1 complex is
      still elusive. Considering the role of RAP80 in the recruitment of BRCA1 complex
      at the DNA damage site, we attempted to explore the molecular mechanism
      associated with RAP80 and mutation that causes chromosomal aberrations due to its
      loss of function. There is a significant loss in structural characteristics of
      RAP80 DeltaE81, which impairs its binding affinity with the polyubiquitin chain.
      This leads to the defective recruitment of RAP80 and BRCA1 complex at the DNA
      damage site. The results presented here are very useful in understanding the
      cause of various repair defects (chromosomal aberration) that arise due to this
      mutation. Comparative study of wild type and DeltaE81 could be helpful in
      designing the small molecules that can potentially compensate the deleterious
      effect(s) of DeltaE81 and hence useful for therapeutic application. 

PMID- 24039797
TI  - Prospective study on the effectiveness of complementary food supplements on
      improving status of elder infants and young children in the areas affected by
      Wenchuan earthquake.
AB  - OBJECTIVE: To prospectively evaluate the efficiency of daily providing
      complementary food supplements decreasing malnutrition and anemia prevalence in
      elder infants and young children living in areas affected by Wenchuan Earthquake.
      DESIGN: Using promotional probability sampling method, 250 to 300 children from
      six-randomized townships (30 to 50 children in each township) in Kang County
      affected by the Earthquake were randomly chosen for follow up to evaluate
      intervention effectiveness using anthropometric measurement and hemoglobin level
      at six, twelve and eighteen months after start of intervention. SETTING AND
      SUBJECTS: All children from 6 to 18 months of age in Kang County (in North
      Western China) were daily provided with complementary food supplements containing
      multiple vitamins and minerals for up to 24 months of age. The intervention
      period lasted for one and half year. RESULTS: At beginning of intervention,
      malnutrition prevalence, including underweight, stunting and wasting were
      respectively 4.5%, 8.9% and 3.5%; anemia prevalence was 74.3%. After one and half
      year intervention, the growth and anemia status were significantly improved; the
      percentages of wasting, stunting underweight prevalence were decreased from 3.5%,
      8.9% and 4.5% to 1.7%, 5.0% and 3.3% respectively, and the anemia rates were
      significantly decreased. CONCLUSIONS: Our results indicated that an intervention
      using complementary food supplements could improve nutritional status and elevate
      hemoglobin level in elder infants and young children, which would significantly
      decrease the prevalence of malnutrition and anemia.

PMID- 24039798
TI  - NMR structure of temporin-1 ta in lipopolysaccharide micelles: mechanistic
      insight into inactivation by outer membrane.
AB  - BACKGROUND: Antimicrobial peptides (AMPs) play important roles in the innate
      defense mechanism. The broad spectrum of activity of AMPs requires an efficient
      permeabilization of the bacterial outer and inner membranes. The outer leaflet of
      the outer membrane of Gram negative bacteria is made of a specialized lipid
      called lipopolysaccharide (LPS). The LPS layer is an efficient permeability
      barrier against anti-bacterial agents including AMPs. As a mode of protection,
      LPS can induce self associations of AMPs rendering them inactive. Temporins are a
      group of short-sized AMPs isolated from frog skin, and many of them are inactive
      against Gram negative bacteria as a result of their self-association in the LPS
      outer membrane. PRINCIPAL FINDINGS: Using NMR spectroscopy, we have determined
      atomic resolution structure and characterized localization of temporin-1Ta or TA
      (FLPLIGRVLSGIL-amide) in LPS micelles. In LPS micelles, TA adopts helical
      conformation for residues L4-I12, while residues F1-L3 are found to be in
      extended conformations. The aromatic sidechain of residue F1 is involved in
      extensive packing interactions with the sidechains of residues P3, L4 and I5.
      Interestingly, a number of long-range NOE contacts have been detected between the
      N-terminal residues F1, P3 with the C-terminal residues S10, I12, L13 of TA in
      LPS micelles. Saturation transfer difference (STD) NMR studies demonstrate close
      proximity of residues including F1, L2, P3, R7, S10 and L13 with the LPS
      micelles. Notably, the LPS bound structure of TA shows differences with the
      structures of TA determined in DPC and SDS detergent micelles. SIGNIFICANCE: We
      propose that TA, in LPS lipids, forms helical oligomeric structures employing N-
      and C-termini residues. Such oligomeric structures may not be translocated across
      the outer membrane; resulting in the inactivation of the AMP. Importantly, the
      results of our studies will be useful for the development of antimicrobial agents
      with a broader spectrum of activity.

PMID- 24039799
TI  - "Dot COM", a nuclear transit center for the primary piRNA pathway in Drosophila.
AB  - The piRNA pathway protects genomes by silencing mobile elements. Despite advances
      in understanding the processing events that generate piRNAs for silencing, little
      is known about how primary transcripts are transported from their genomic
      clusters to their processing centers. Using a model of the Drosophila
      COM/flamenco locus in ovarian somatic cells, we identified a prominent nuclear
      structure called Dot COM, which is enriched in long transcripts from piRNA
      clusters but located far from their transcription sites. Remarkably, transcripts
      from multiple clusters accumulate at Dot COM, which is often juxtaposed with Yb
      bodies, the cytoplasmic processing centers for cluster transcripts. Genetic
      evidence suggests that the accumulation of precursor transcripts at Dot COM
      represents one of the most upstream events in the piRNA pathway. Our results
      provide new insights into the initial steps of the piRNA pathway, and open up a
      new research area important for a complete understanding of this conserved
      pathway. 

PMID- 24039800
TI  - Eight nucleotide substitutions inhibit splicing to HPV-16 3'-splice site SA3358
      and reduce the efficiency by which HPV-16 increases the life span of primary
      human keratinocytes.
AB  - The most commonly used 3'-splice site on the human papillomavirus type 16 (HPV
      16) genome named SA3358 is used to produce HPV-16 early mRNAs encoding E4, E5, E6
      and E7, and late mRNAs encoding L1 and L2. We have previously shown that SA3358
      is suboptimal and is totally dependent on a downstream splicing enhancer
      containingmultiple potential ASF/SF2 binding sites. Here weshow that only one of
      the predicted ASF/SF2 sites accounts for the majority of the enhancer activity.
      We demonstrate that single nucleotide substitutions in this predicted ASF/SF2
      site impair enhancer function and that this correlates with less efficient
      binding to ASF/SF2 in vitro. We provide evidence that HPV-16 mRNAs that
      arespliced to SA3358 interact with ASF/SF2 in living cells. In
      addition,mutational inactivation of the ASF/SF2 site weakened the enhancer at
      SA3358 in episomal forms of the HPV-16 genome, indicating that the enhancer is
      active in the context of the full HPV-16 genome.This resulted in induction of HPV
      16 late gene expression as a result of competition from late splice site SA5639.
      Furthermore, inactivation of the ASF/SF2 site of the SA3358 splicing enhancer
      reduced the ability of E6- and E7-encoding HPV-16 plasmids to increase the life
      span of primary keratinocytes in vitro, demonstrating arequirement for an intact
      splicing enhancer of SA3358 forefficient production of the E6 and E7 mRNAs. These
      results link the strength of the HPV-16 SA3358 splicing enhancer to expression of
      E6 and E7 and to the pathogenic properties of HPV-16. 

PMID- 24039801
TI  - The extraction of simple relationships in growth factor-specific multiple-input
      and multiple-output systems in cell-fate decisions by backward elimination PLS
      regression.
AB  - Cells use common signaling molecules for the selective control of downstream gene
      expression and cell-fate decisions. The relationship between signaling molecules
      and downstream gene expression and cellular phenotypes is a multiple-input and
      multiple-output (MIMO) system and is difficult to understand due to its
      complexity. For example, it has been reported that, in PC12 cells, different
      types of growth factors activate MAP kinases (MAPKs) including ERK, JNK, and p38,
      and CREB, for selective protein expression of immediate early genes (IEGs) such
      as c-FOS, c-JUN, EGR1, JUNB, and FOSB, leading to cell differentiation,
      proliferation and cell death; however, how multiple-inputs such as MAPKs and CREB
      regulate multiple-outputs such as expression of the IEGs and cellular phenotypes
      remains unclear. To address this issue, we employed a statistical method called
      partial least squares (PLS) regression, which involves a reduction of the
      dimensionality of the inputs and outputs into latent variables and a linear
      regression between these latent variables. We measured 1,200 data points for
      MAPKs and CREB as the inputs and 1,900 data points for IEGs and cellular
      phenotypes as the outputs, and we constructed the PLS model from these data. The
      PLS model highlighted the complexity of the MIMO system and growth factor
      specific input-output relationships of cell-fate decisions in PC12 cells.
      Furthermore, to reduce the complexity, we applied a backward elimination method
      to the PLS regression, in which 60 input variables were reduced to 5 variables,
      including the phosphorylation of ERK at 10 min, CREB at 5 min and 60 min, AKT at
      5 min and JNK at 30 min. The simple PLS model with only 5 input variables
      demonstrated a predictive ability comparable to that of the full PLS model. The 5
      input variables effectively extracted the growth factor-specific simple
      relationships within the MIMO system in cell-fate decisions in PC12 cells. 

PMID- 24039802
TI  - Accumulation of biomass and mineral elements with calendar time by cotton:
      application of the expanded growth model.
AB  - Accumulation of plant biomass (Mg ha(-1)) with calendar time (wk) occurs as a
      result of photosynthesis for green land-based plants. A corresponding
      accumulation of mineral elements (kg ha(-1)) such as nitrogen, phosphorus, and
      potassium occurs from the soil through plant roots. Field data from literature
      for the warm-season annual cotton (Gossypium hirsutum L.) are used in this
      analysis. The expanded growth model is used to describe accumulation of biomass
      and mineral elements with calendar time. The growth model predicts a simple
      linear relationship between biomass yield and the growth quantifier, which is
      confirmed with the data. The growth quantifier incorporates the unit processes of
      distribution of solar energy which drives biomass accumulation by photosynthesis,
      partitioning of biomass between light-gathering and structural components of the
      plants, and an aging function. A hyperbolic relationship between plant nutrient
      uptake and biomass yield is assumed, and is confirmed for the mineral elements
      nitrogen, phosphorus, and potassium. It is concluded that the rate limiting
      process in the system is biomass accumulation by photosynthesis and that nutrient
      accumulation occurs in virtual equilibrium with biomass accumulation. The
      expanded growth model describes field data from California and Alabama rather
      well. Furthermore, all model parameters were common for the two sites with the
      exception of the yield factor A which accounts for differences in soil types,
      environmental conditions, fertilizer levels, and plant population. 

PMID- 24039804
TI  - Awareness of HIV testing guidelines is low among Swiss emergency doctors: a
      survey of five teaching hospitals in French-speaking Switzerland.
AB  - BACKGROUND: In Switzerland, 30% of HIV-infected individuals are diagnosed late.
      To optimize HIV testing, the Swiss Federal Office of Public Health (FOPH) updated
      'Provider Induced Counseling and Testing' (PICT) recommendations in 2010. These
      permit doctors to test patients if HIV infection is suspected, without explicit
      consent or pre-test counseling; patients should nonetheless be informed that
      testing will be performed. We examined awareness of these updated recommendations
      among emergency department (ED) doctors. METHODS: We conducted a questionnaire
      based survey among 167 ED doctors at five teaching hospitals in French-Speaking
      Switzerland between 1(st) May and 31(st) July 2011. For 25 clinical scenarios,
      participants had to state whether HIV testing was indicated or whether patient
      consent or pre-test counseling was required. We asked how many HIV tests
      participants had requested in the previous month, and whether they were aware of
      the FOPH testing recommendations. RESULTS: 144/167 doctors (88%) returned the
      questionnaire. Median postgraduate experience was 6.5 years (interquartile range
      [IQR] 3; 12). Mean percentage of correct answers was 59 +/- 11%, senior doctors
      scoring higher (P=0.001). Lowest-scoring questions pertained to acute HIV
      infection and scenarios where patient consent was not required. Median number of
      test requests was 1 (IQR 0-2, range 0-10). Only 26/144 (18%) of participants were
      aware of the updated FOPH recommendations. Those aware had higher scores
      (P=0.001) but did not perform more HIV tests. CONCLUSIONS: Swiss ED doctors are
      not aware of the national HIV testing recommendations and rarely perform HIV
      tests. Improved recommendation dissemination and adherence is required if ED
      doctors are to contribute to earlier HIV diagnoses.

PMID- 24039803
TI  - Epidemiological and genetic diversity of Staphylococcus aureus causing
      bloodstream infection in Shanghai, 2009-2011.
AB  - OBJECTIVES: Staphylococcus aureus or methicillin-resistant Staphylococcus aureus
      (MRSA) has been an important pathogen causing bloodstream infections. Our study
      aimed to investigate the epidemiological and genetic diversity of clinical S.
      aureus isolates from patients with bloodstream infection in four hospitals of
      Shanghai from 2009 to 2011. METHODS: A collection of S. aureus isolates causing
      bloodstream infection from four hospitals in the central part of Shanghai was
      carried out. Antimicrobial susceptibility testings of collected isolates were
      performed according to the Clinical and Laboratory Standards Institute (CLSI)
      guidelines, and spa-type, multi-locus sequence typing, agr type and toxin gene
      profiling were performed to explore the molecular diversity. Moreover, MRSA
      strains were also characterized by Staphylococcal cassette chromosome mec
      (SCCmec) typing. RESULTS: The drugs such as linezolid, teicoplanin and vancomycin
      were efficacious for treating S. aureus including MRSA bloodstream infection.
      Methicillin-sensitive Staphylococcus aureus (MSSA) strains displayed distinct
      diversity in molecular characterization and toxin genes, and three virulent MSSA
      strains encoding at least five toxins were detected. Five community-associated
      MRSA (CA-MRSA) strains were found, but the majority (88.7%) of MRSA strains
      belonged to two epidemic clones (ST239-MRSA- III and ST5-MRSA- II) with different
      toxin gene profiles among patients with bloodstream infection. CONCLUSIONS:
      Healthcare-associated MRSA (HA-MRSA) strains were still the main pathogen causing
      bloodstream infections in spite of the emergence of CA-MRSA strains in hospital
      setting.

PMID- 24039805
TI  - Revising the taxonomic distribution, origin and evolution of ribosome
      inactivating protein genes.
AB  - Ribosome inactivating proteins are enzymes that depurinate a specific adenine
      residue in the alpha-sarcin-ricin loop of the large ribosomal RNA, being ricin
      and Shiga toxins the most renowned examples. They are widely distributed in
      plants and their presence has also been confirmed in a few bacterial species.
      According to this taxonomic distribution, the current model about the origin and
      evolution of RIP genes postulates that an ancestral RIP domain was originated in
      flowering plants, and later acquired by some bacteria via horizontal gene
      transfer. Here, we unequivocally detected the presence of RIP genes in fungi and
      metazoa. These findings, along with sequence and phylogenetic analyses, led us to
      propose an alternative, more parsimonious, hypothesis about the origin and
      evolutionary history of the RIP domain, where several paralogous RIP genes were
      already present before the three domains of life evolved. This model is in
      agreement with the current idea of the Last Universal Common Ancestor (LUCA) as a
      complex, genetically redundant organism. Differential loss of paralogous genes in
      descendants of LUCA, rather than multiple horizontal gene transfer events, could
      account for the complex pattern of RIP genes across extant species, as it has
      been observed for other genes. 

PMID- 24039806
TI  - Prevalence and molecular characterization of methicillin-resistant Staphylococcus
      aureus ST398 resistant to tetracycline at a Spanish hospital over 12 years.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) ST398, associated with
      livestock animals, was described in 2003 as a new lineage infecting or colonizing
      humans. We evaluated the prevalence and molecular characteristics of MRSA ST398
      isolated in the Hospital Universitari de Bellvitge from January 2000 to June
      2011. Tetracycline resistant (Tet-R) MRSA isolates from single patients (pts)
      were screened by SmaI-pulsed field gel electrophoresis (PFGE). Nontypable MRSA
      strains by SmaI (NT Sma I)-MRSA were further analysed by ApaI-PFGE, spa, SCCmec,
      agr, MLST typing, and by DNA microarray hybridization. Among 164 pts harboring
      Tet-R MRSA, NT Sma I-MRSA ST398-agrI was found in 33 pts (20%). Although the
      first pt was detected in 2003, 22/33 pts (67%) were registered in the 2010-2011
      period. Ten pts (30%) were infected and cancer was the most frequent underlying
      disease. In one case, death was due to MRSA-ST398-related infection. Five
      pulsotypes (A-E) were detected using ApaI-PFGE, with type A accounting for 76% of
      the strains. The majority of the studied isolates presented spa type t011 (70%)
      and SCCmec type V (88%). One strain was spa negative both by PCR and microarray
      analysis. Forty-nine percent of the studied isolates showed resistance to 3 or
      more antibiotic classes, in addition to beta-lactams. Ciprofloxacin resistance
      was 67%. Tet-R was mediated by tet(M) and tet(K) in 26 isolates. All isolates
      lacked Panton-Valentine Leukocidin production, as well as other significant
      toxins. This study displays the molecular features of MRSA-ST398 clone and shows
      the increase in tetracycline resistance together with arise in MRSA-ST398
      isolates infecting or colonizing patients in our clinical setting. 

PMID- 24039807
TI  - Ecological complexity of coral recruitment processes: effects of invertebrate
      herbivores on coral recruitment and growth depends upon substratum properties and
      coral species.
AB  - BACKGROUND: The transition from planktonic planula to sessile adult corals occurs
      at low frequencies and post settlement mortality is extremely high. Herbivores
      promote settlement by reducing algal competition. This study investigates whether
      invertebrate herbivory might be modulated by other ecological factors such as
      substrata variations and coral species identity. METHODOLOGY/PRINCIPAL FINDINGS:
      The experiment was conducted at the Flower Garden Banks, one of the few Atlantic
      reefs not experiencing considerable degradation. Tiles of differing texture and
      orientation were kept in bins surrounded by reef (24 m). Controls contained no
      herbivores while treatment bins contained urchins (Diadema antillarum) or
      herbivorous gastropods (Cerithium litteratum). Juvenile corals settling naturally
      were monitored by photography for 14 months to evaluate the effects of
      invertebrate herbivory and substratum properties. Herbivory reduced algae cover
      in urchin treatments. Two genera of brooding coral juveniles were observed,
      Agaricia and Porites, both of which are common but not dominant on adjacent reef.
      No broadcast spawning corals were observed on tiles. Overall, juveniles were more
      abundant in urchin treatments and on vertical, rough textured surfaces. Although
      more abundant, Agaricia juveniles were smaller in urchin treatments, presumably
      due to destructive overgrazing. Still, Agaricia growth increased with herbivory
      and substrata texture-orientation interactions were observed with reduced growth
      on rough tiles in control treatments and increased growth on vertical tiles in
      herbivore treatments. In contrast to Agaricia, Porites juveniles were larger on
      horizontal tiles, irrespective of herbivore treatment. Mortality was affected by
      substrata orientation with vertical surfaces increasing coral survival.
      CONCLUSIONS/SIGNIFICANCE: We further substantiate that invertebrate herbivores
      play major roles in early settlement processes of corals and highlight the need
      for deeper understanding of ecological interactions modulating these effects. The
      absence of broadcast-spawning corals, even on a reef with consistently high coral
      cover, continues to expose the recruitment failure of these reef-building corals
      throughout the Caribbean.

PMID- 24039808
TI  - Seven to eight hours of sleep a night is associated with a lower prevalence of
      the metabolic syndrome and reduced overall cardiometabolic risk in adults.
AB  - BACKGROUND: Previous studies looking at the relationship between sleep duration
      and the metabolic syndrome have only used a dichotomous approach
      (presence/absence) and failed to adjust for important confounding factors. The
      objective of the present study was to examine the association between self
      reported sleep duration and features of the metabolic syndrome in adults.
      METHODS: A cross-sectional analysis from the Quebec Family Study (Canada) was
      conducted on 810 participants aged 18 to 65 years. Participants were categorized
      as short (<=6 h), adequate (7-8 h) or long (>=9 h) sleepers. The metabolic
      syndrome was defined according to the American Heart Association/National Heart,
      Lung, and Blood Institute's criteria. RESULTS: Overall, 24.6% of the sample had
      the metabolic syndrome. A U-shaped relationship between sleep duration and the
      prevalence of metabolic syndrome (33.3%, 22.0% and 28.8% in short, adequate and
      long sleepers, respectively) was observed (P<0.01). Only short sleepers had a
      significant increase in the odds of having the metabolic syndrome (OR = 1.76, 95%
      CI = 1.08-2.84) compared to adequate sleepers after adjustment for age, sex,
      smoking habits, highest education level, total annual family income, alcohol
      consumption, coffee intake, menopausal status, daily caloric intake, and moderate
      to-vigorous physical activity. Likewise, the clustered cardiometabolic risk score
      (i.e. continuous risk score based on the metabolic syndrome components) was
      significantly higher in short sleepers compared to adequate sleepers after
      adjustment for covariates (P<0.05). CONCLUSION: Sleeping <=6 h per night is
      associated with an elevated cardiometabolic risk score and an increase in the
      odds of having the metabolic syndrome after adjusting for possible confounders.
      These results strongly suggest that short sleep duration is a risk factor for the
      metabolic syndrome.

PMID- 24039809
TI  - Global features of gene expression on the proteome and transcriptome levels in S.
      coelicolor during germination.
AB  - Streptomycetes have been studied mostly as producers of secondary metabolites,
      while the transition from dormant spores to an exponentially growing culture has
      largely been ignored. Here, we focus on a comparative analysis of fluorescently
      and radioactively labeled proteome and microarray acquired transcriptome
      expressed during the germination of Streptomyces coelicolor. The time-dynamics is
      considered, starting from dormant spores through 5.5 hours of growth with 13 time
      points. Time series of the gene expressions were analyzed using correlation,
      principal components analysis and an analysis of coding genes utilization.
      Principal component analysis was used to identify principal kinetic trends in
      gene expression and the corresponding genes driving S. coelicolor germination. In
      contrast with the correlation analysis, global trends in the gene/protein
      expression reflected by the first principal components showed that the prominent
      patterns in both the protein and the mRNA domains are surprisingly well
      correlated. Analysis of the number of expressed genes identified functional
      groups activated during different time intervals of the germination. 

PMID- 24039810
TI  - RosettaEPR: rotamer library for spin label structure and dynamics.
AB  - An increasingly used parameter in structural biology is the measurement of
      distances between spin labels bound to a protein. One limitation to these
      measurements is the unknown position of the spin label relative to the protein
      backbone. To overcome this drawback, we introduce a rotamer library of the
      methanethiosulfonate spin label (MTSSL) into the protein modeling program
      Rosetta. Spin label rotamers were derived from conformations observed in crystal
      structures of spin labeled T4 lysozyme and previously published molecular
      dynamics simulations. Rosetta's ability to accurately recover spin label
      conformations and EPR measured distance distributions was evaluated against 19
      experimentally determined MTSSL labeled structures of T4 lysozyme and the
      membrane protein LeuT and 73 distance distributions from T4 lysozyme and the
      membrane protein MsbA. For a site in the core of T4 lysozyme, the correct spin
      label conformation (Chi1 and Chi2) is recovered in 99.8% of trials. In surface
      positions 53% of the trajectories agree with crystallized conformations in Chi1
      and Chi2. This level of recovery is on par with Rosetta performance for the 20
      natural amino acids. In addition, Rosetta predicts the distance between two spin
      labels with a mean error of 4.4 A. The width of the experimental distance
      distribution, which reflects the flexibility of the two spin labels, is predicted
      with a mean error of 1.3 A. RosettaEPR makes full-atom spin label modeling
      available to a wide scientific community in conjunction with the powerful suite
      of modeling methods within Rosetta. 

PMID- 24039811
TI  - Quantifying memory in complex physiological time-series.
AB  - In a time-series, memory is a statistical feature that lasts for a period of time
      and distinguishes the time-series from a random, or memory-less, process. In the
      present study, the concept of "memory length" was used to define the time period,
      or scale over which rare events within a physiological time-series do not appear
      randomly. The method is based on inverse statistical analysis and provides
      empiric evidence that rare fluctuations in cardio-respiratory time-series are
      'forgotten' quickly in healthy subjects while the memory for such events is
      significantly prolonged in pathological conditions such as asthma (respiratory
      time-series) and liver cirrhosis (heart-beat time-series). The memory length was
      significantly higher in patients with uncontrolled asthma compared to healthy
      volunteers. Likewise, it was significantly higher in patients with decompensated
      cirrhosis compared to those with compensated cirrhosis and healthy volunteers. We
      also observed that the cardio-respiratory system has simple low order dynamics
      and short memory around its average, and high order dynamics around rare
      fluctuations. 

PMID- 24039812
TI  - Detection of magnetic field intensity gradient by homing pigeons (Columba livia)
      in a novel "virtual magnetic map" conditioning paradigm.
AB  - It has long been thought that birds may use the Earth's magnetic field not only
      as a compass for direction finding, but that it could also provide spatial
      information for position determination analogous to a map during navigation.
      Since magnetic field intensity varies systematically with latitude and
      theoretically could also provide longitudinal information during position
      determination, birds using a magnetic map should be able to discriminate magnetic
      field intensity cues in the laboratory. Here we demonstrate a novel behavioural
      paradigm requiring homing pigeons to identify the direction of a magnetic field
      intensity gradient in a "virtual magnetic map" during a spatial conditioning
      task. Not only were the pigeons able to detect the direction of the intensity
      gradient, but they were even able to discriminate upward versus downward movement
      on the gradient by differentiating between increasing and decreasing intensity
      values. Furthermore, the pigeons typically spent more than half of the 15 second
      sampling period in front of the feeder associated with the rewarded gradient
      direction indicating that they required only several seconds to make the correct
      choice. Our results therefore demonstrate for the first time that pigeons not
      only can detect the presence and absence of magnetic anomalies, as previous
      studies had shown, but are even able to detect and respond to changes in magnetic
      field intensity alone, including the directionality of such changes, in the
      context of spatial orientation within an experimental arena. This opens up the
      possibility for systematic and detailed studies of how pigeons could use magnetic
      intensity cues during position determination as well as how intensity is
      perceived and where it is processed in the brain. 

PMID- 24039813
TI  - Changes in recognition memory over time: an ERP investigation into vocabulary
      learning.
AB  - Although it seems intuitive to assume that recognition memory fades over time
      when information is not reinforced, some aspects of word learning may benefit
      from a period of consolidation. In the present study, event-related potentials
      (ERP) were used to examine changes in recognition memory responses to familiar
      and newly learned (novel) words over time. Native English speakers were taught
      novel words associated with English translations, and subsequently performed a
      Recognition Memory task in which they made old/new decisions in response to both
      words (trained word vs. untrained word), and novel words (trained novel word vs.
      untrained novel word). The Recognition task was performed 45 minutes after
      training (Day 1) and then repeated the following day (Day 2) with no additional
      training session in between. For familiar words, the late parietal old/new effect
      distinguished old from new items on both Day 1 and Day 2, although response to
      trained items was significantly weaker on Day 2. For novel words, the LPC again
      distinguished old from new items on both days, but the effect became
      significantly larger on Day 2. These data suggest that while recognition memory
      for familiar items may fade over time, recognition of novel items, conscious
      recollection in particular may benefit from a period of consolidation. 

PMID- 24039814
TI  - Thymoquinone inhibits autophagy and induces cathepsin-mediated, caspase
      independent cell death in glioblastoma cells.
AB  - Glioblastoma is the most aggressive and common type of malignant brain tumor in
      humans, with a median survival of 15 months. There is a great need for more
      therapies for the treatment of glioblastoma. Naturally occurring phytochemicals
      have received much scientific attention because many exhibit potent tumor killing
      action. Thymoquinone (TQ) is the bioactive compound of the Nigella sativa seed
      oil. TQ has anti-oxidant, anti-inflammatory and anti-neoplastic actions with
      selective cytotoxicity for human cancer cells compared to normal cells. Here, we
      show that TQ selectively inhibits the clonogenicity of glioblastoma cells as
      compared to normal human astrocytes. Also, glioblastoma cell proliferation could
      be impaired by chloroquine, an autophagy inhibitor, suggesting that glioblastoma
      cells may be dependent on the autophagic pathway for survival. Exposure to TQ
      caused an increase in the recruitment and accumulation of the microtubule
      associated protein light chain 3-II (LC3-II). TQ also caused an accumulation of
      the LC3-associated protein p62, confirming the inhibition of autophagy.
      Furthermore, the levels of Beclin-1 protein expression were unchanged, indicating
      that TQ interferes with a later stage of autophagy. Finally, treatment with TQ
      induces lysosome membrane permeabilization, as determined by a specific loss of
      red acridine orange staining. Lysosome membrane permeabilization resulted in a
      leakage of cathepsin B into the cytosol, which mediates caspase-independent cell
      death that can be prevented by pre-treatment with a cathepsin B inhibitor. TQ
      induced apoptosis, as determined by an increase in PI and Annexin V positive
      cells. However, apoptosis appears to be caspase-independent due to failure of the
      caspase inhibitor z-VAD-FMK to prevent cell death and absence of the typical
      apoptosis related signature DNA fragmentation. Inhibition of autophagy is an
      exciting and emerging strategy in cancer therapy. In this vein, our results
      describe a novel mechanism of action for TQ as an autophagy inhibitor selectively
      targeting glioblastoma cells. 

PMID- 24039815
TI  - Drug-eluting stents for acute coronary syndrome: a meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Drug-eluting stents (DES) are increasingly used for treatment of
      acute coronary syndrome (ACS). However, clinical efficacy and safety of various
      types of DES is not well established in these subjects. We therefore evaluated
      clinical utility of second-generation and first-generation DES in patients with
      ACS by conducting a meta-analysis. METHODS: A search of Medline, Embase, the
      Cochrane databases, and Web of Science was made. Randomized controlled trials
      (RCTs) which compared second-generation DES (everolimus-eluting stents [EES] or
      zotarolimus-eluting stents [ZES]) versus first-generation DES (sirolimus-eluting
      stents [SES] or paclitaxe-eluting stents [PES]) in patients with ACS and provided
      data on clinical efficacy or safety endpoints were included. Pooled estimates
      were calculated using random-effects model. RESULT: A total of 2,757 participants
      with ACS in 6 RCTs were included. Compared with first-generation one, second
      generation DES trended to be associated with the decreased incidence of definite
      or probable stent thrombosis in ACS patients (risk ratio [RR]  = 0.60, 95%
      confidence intervals [CI] 0.33 to 1.07, p = 0.09). However, the rate of target
      lesion revascularization (TLR) significantly increased in second-generation DES
      (RR = 2.08, 95%CI 1.25 to 3.47, p = 0.005). There were no significant differences
      in the incidence of major adverse cardiac events (MACEs), all-cause death,
      cardiac death, and recurrent myocardial infarction between the two arms (all
      p>0.10). The second-generation EES showed a tendency towards lower risk of MACEs
      (p = 0.06) and a beneficial effect on reducing stent thrombosis episodes (p =
      0.009), while the second-generation ZES presented an increased occurrence of
      MACEs (p = 0.02) and TLR (p = 0.003). CONCLUSION: Second-generation DES,
      especially EES, appeared to present a lower risk of stent thrombosis, whereas
      second-generation ZES might increase the need for repeat revascularization in ACS
      patients. During coronary interventional therapy, DES class should be adequately
      considered in order to maximize clinical benefit of DES implantation in these
      specific subjects.

PMID- 24039816
TI  - Mechanistic comparison between gastric bypass vs. duodenal switch with sleeve
      gastrectomy in rat models.
AB  - BACKGROUND: Both gastric bypass (GB) and duodenal switch with sleeve gastrectomy
      (DS) have been widely used as bariatric surgeries, and DS appears to be superior
      to GB. The aim of this study was to better understand the mechanisms leading to
      body weight loss by comparing these two procedures in experimental models of
      rats. METHODS: Animals were subjected to GB, DS or laparotomy (controls), and
      monitored by an open-circuit indirect calorimeter composed of comprehensive
      laboratory animal monitoring system and adiabatic bomb calorimeter. RESULTS: Body
      weight loss was greater after DS than GB. Food intake was reduced after DS but
      not GB. Energy expenditure was increased after either GB or DS. Fecal energy
      content was increased after DS but not GB. CONCLUSION: GB induced body weight
      loss by increasing energy expenditure, whereas DS induced greater body weight
      loss by reducing food intake, increasing energy expenditure and causing
      malabsorption in rat models.

PMID- 24039817
TI  - Age of onset of RNA toxicity influences phenotypic severity: evidence from an
      inducible mouse model of myotonic dystrophy (DM1).
AB  - Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults.
      It is caused by an expanded (CTG)n tract in the 3' UTR of the Dystrophia
      Myotonica Protein Kinase (DMPK) gene. This causes nuclear retention of the mutant
      mRNA into ribonuclear foci and sequestration of interacting RNA-binding proteins
      (such as muscleblind-like 1 (MBNL1)). More severe congenital and childhood-onset
      forms of the disease exist but are less understood than the adult disease, due in
      part to the lack of adequate animal models. To address this, we utilized
      transgenic mice over-expressing the DMPK 3' UTR as part of an inducible RNA
      transcript to model early-onset myotonic dystrophy. In mice in which transgene
      expression was induced during embryogenesis, we found that by two weeks after
      birth, mice reproduced cardinal features of myotonic dystrophy, including
      myotonia, cardiac conduction abnormalities, muscle weakness, histopathology and
      mRNA splicing defects. Notably, these defects were more severe than in adult mice
      induced for an equivalent period of exposure to RNA toxicity. Additionally, the
      utility of the model was tested by over-expressing MBNL1, a key therapeutic
      strategy being actively pursued for treating the disease phenotypes associated
      with DM1. Significantly, increased MBNL1 in skeletal muscle partially corrected
      myotonia and splicing defects present in these mice, demonstrating the
      responsiveness of the model to relevant therapeutic interventions. Furthermore,
      these results also represent the first murine model for early-onset DM1 and
      provide a tool to investigate the effects of RNA toxicity at various stages of
      development. 

PMID- 24039818
TI  - Correlations between community structure and link formation in complex networks.
AB  - BACKGROUND: Links in complex networks commonly represent specific ties between
      pairs of nodes, such as protein-protein interactions in biological networks or
      friendships in social networks. However, understanding the mechanism of link
      formation in complex networks is a long standing challenge for network analysis
      and data mining. METHODOLOGY/PRINCIPAL FINDINGS: Links in complex networks have a
      tendency to cluster locally and form so-called communities. This widely existed
      phenomenon reflects some underlying mechanism of link formation. To study the
      correlations between community structure and link formation, we present a general
      computational framework including a theory for network partitioning and link
      probability estimation. Our approach enables us to accurately identify missing
      links in partially observed networks in an efficient way. The links having high
      connection likelihoods in the communities reveal that links are formed
      preferentially to create cliques and accordingly promote the clustering level of
      the communities. The experimental results verify that such a mechanism can be
      well captured by our approach. CONCLUSIONS/SIGNIFICANCE: Our findings provide a
      new insight into understanding how links are created in the communities. The
      computational framework opens a wide range of possibilities to develop new
      approaches and applications, such as community detection and missing link
      prediction.

PMID- 24039819
TI  - Transcript assembly and quantification by RNA-Seq reveals differentially
      expressed genes between soft-endocarp and hard-endocarp hawthorns.
AB  - Hawthorn (Crataegus spp.) is an important pome with a long history as a fruit, an
      ornamental, and a source of medicine. Fruits of hawthorn are marked by hard stony
      endocarps, but a hawthorn germplasm with soft and thin endocarp was found in
      Liaoning province of China. To elucidate the molecular mechanism underlying the
      soft endocarp of hawthorn, we conducted a de novo assembly of the fruit
      transcriptome of Crataegus pinnatifida and compared gene expression profiles
      between the soft-endocarp and the hard-endocarp hawthorn varieties. De novo
      assembly yielded 52,673 putative unigenes, 20.4% of which are longer than 1,000
      bp. Among the high-quality unique sequences, 35,979 (68.3%) had at least one
      significant match to an existing gene model. A total of 1,218 genes, represented
      2.31% total putative unigenes, were differentially expressed between the soft
      endocarp hawthorn and the hard-endocarp hawthorn. Among these differentially
      expressed genes, a number of lignin biosynthetic pathway genes were down
      regulated while almost all the flavonoid biosynthetic pathway genes were strongly
      up-regulated, concomitant with the formation of soft endocarp. In addition, we
      have identified some MYB and NAC transcription factors that could potentially
      control lignin and flavonoid biosynthesis. The altered expression levels of the
      genes encoding lignin biosynthetic enzymes, MYB and NAC transcription factors
      were confirmed by quantitative RT-PCR. This is the first transcriptome analysis
      of Crataegus genus. The high quality ESTs generated in this study will aid future
      gene cloning from hawthorn. Our study provides important insights into the
      molecular mechanisms underlying soft endocarp formation in hawthorn. 

PMID- 24039820
TI  - Fish oil and atrial fibrillation after cardiac surgery: a meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Influence of fish oil supplementation on postoperative atrial
      fibrillation (POAF) was inconsistent according to published clinical trials. The
      aim of the meta-analysis was to evaluate the effects of perioperative fish oil
      supplementation on the incidence of POAF after cardiac surgery. METHODS: Pubmed,
      Embase and the Cochrane Library databases were searched. Randomized controlled
      trials (RCTs) assessing perioperative fish oil supplementation for patients
      undergoing cardiac surgery were identified. Data concerning study design, patient
      characteristics, and outcomes were extracted. Risk ratio (RR) and weighted mean
      differences (WMD) were calculated using fixed or random effects models. RESULTS:
      Eight RCTs involving 2687 patients were included. Perioperative supplementation
      of fish oil did not significantly reduce the incidence of POAF (RR = 0.86, 95%CI
      0.71 to 1.03, p = 0.11) or length of hospitalization after surgery (WMD = 0.10
      days, 95% CI: 0.48 to 0.67 days, p = 0.75). Fish oil supplementation also did not
      affect the perioperative mortality, incidence of major bleeding or the length of
      stay in the intensive care unit. Meta-regression and subgroup analyses indicated
      mean DHA dose in the supplements may be a potential modifier for the effects of
      fish oil for POAF. For supplements with DHA >1 g/d, fish oil significantly
      reduced the incidence of POAF; while it did not for the supplements with a lower
      dose of DHA. CONCLUSIONS: Current evidence did not support a preventative role of
      fish oil for POAF. However, relative amounts of DHA and EPA in fish oil may be
      important for the prevention of POAF.

PMID- 24039821
TI  - AbaA regulates conidiogenesis in the ascomycete fungus Fusarium graminearum.
AB  - Fusarium graminearum (teleomorph Gibberella zeae) is a prominent pathogen that
      infects major cereal crops such as wheat, barley, and maize. Both sexual
      (ascospores) and asexual (conidia) spores are produced in F. graminearum. Since
      conidia are responsible for secondary infection in disease development, our
      objective of the present study was to reveal the molecular mechanisms underlying
      conidiogenesis in F. graminearum based on the framework previously described in
      Aspergillus nidulans. In this study, we firstly identified and functionally
      characterized the ortholog of AbaA, which is involved in differentiation from
      vegetative hyphae to conidia and known to be absent in F. graminearum. Deletion
      of abaA did not affect vegetative growth, sexual development, or virulence, but
      conidium production was completely abolished and thin hyphae grew from abnormally
      shaped phialides in abaA deletion mutants. Overexpression of abaA resulted in
      pleiotropic defects such as impaired sexual and asexual development, retarded
      conidium germination, and reduced trichothecene production. AbaA localized to the
      nuclei of phialides and terminal cells of mature conidia. Successful interspecies
      complementation using A. nidulans AbaA and the conserved AbaA-WetA pathway
      demonstrated that the molecular mechanisms responsible for AbaA activity are
      conserved in F. graminearum as they are in A. nidulans. Results from RNA
      sequencing analysis suggest that AbaA plays a pivotal role in conidiation by
      regulating cell cycle pathways and other conidiation-related genes. Thus, the
      conserved roles of the AbaA ortholog in both A. nidulans and F. graminearum give
      new insight into the genetics of conidiation in filamentous fungi. 

PMID- 24039822
TI  - Altered white adipose tissue protein profile in C57BL/6J mice displaying
      delipidative, inflammatory, and browning characteristics after bitter melon seed
      oil treatment.
AB  - OBJECTIVE: We have previously shown that bitter melon seed oil (BMSO), which is
      rich in cis-9, trans-11, trans-13 conjugated linolenic acid, is more potent than
      soybean oil in attenuating body fat deposition in high-fat diet-induced obese
      C57BL/6J mice. The aim of this study was to obtain a comprehensive insight into
      how white adipose tissue (WAT) is affected by BMSO administration and to explore
      the underlying mechanisms of the anti-adiposity effect of BMSO. METHODS AND
      RESULTS: A proteomic approach was used to identify proteins differentially
      expressed in the WAT of mice fed diets with or without BMSO for 11 wks. The WAT
      was also analyzed histologically for morphological changes. Two-dimensional gel
      electrophoresis (pH 4-7) revealed 32 spots showing a statistically significant
      difference (P<0.05) in intensity in BMSO-treated mice and 30 of these were shown
      to code for 23 proteins (15 increased and 8 decreased expression; >2-fold
      change). Combined with histological evidence of macrophage infiltration and brown
      adipocyte recruitment, the proteomic and immunoblotting data showed that the WAT
      in mice subjected to long-term high dose BMSO administration was characterized by
      reduced caveolae formation, increased ROS insult, tissue remodeling/repair,
      mitochondria uncoupling, and stabilization of the actin cytoskeleton, this last
      change being putatively related to an increased inflammatory response.
      CONCLUSION: The anti-adiposity effect of BMSO is associated with WAT
      delipidation, inflammation, and browning. Some novel proteins participating in
      these processes were identified. In addition, the BMSO-mediated WAT browning may
      account for the increased inflammation without causing adverse metabolic effects.

PMID- 24039823
TI  - Baicalein inhibits the invasion and metastatic capabilities of hepatocellular
      carcinoma cells via down-regulation of the ERK pathway.
AB  - Baicalein, a widely used Chinese herbal medicine, has historically been used in
      anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect
      and molecular mechanism(s) of baicalein on hepatocellular carcinoma (HCC) remain
      poorly understood. Therefore, the purpose of this study was to assess the anti
      metastatic effects of baicalein and related mechanism(s) on HCC. Based on assays
      utilized in both HCC cell lines and in an animal model, we found that baicalein
      inhibited tumor cell metastasis in vivo and in vitro. Furthermore, after
      treatment with baicalein for 24 hours, there was a decrease in the levels of
      matrix metalloproteinase-2 (MMP-2), MMP-9 and urokinase-type plasminogen
      activator (u-PA) expression as well as proteinase activity in hepatocellular
      carcinoma MHCC97H cells. Meanwhile, the expression of tissue inhibitor of
      metalloproteinase-1 (TIMP-1) and TIMP-2 were increased in a dose-dependent
      fashion. Moreover, baicalein treatment dramatically decreased the levels of the
      phosphorylated forms of MEK1 and ERK1/2. MEK1 overexpression partially blocked
      the anti-metastatic effects of baicalein. Combined treatment with an ERK
      inhibitor (U0126) and baicalein resulted in a synergistic reduction in MMP-2, MMP
      9 and u-PA expression and an increase in TIMP-1 and TIMP-2 expression; the
      invasive capabilities of MHCC97H cells were also inhibited. In conclusion,
      baicalein inhibits tumor cell invasion and metastasis by reducing cell motility
      and migration via the suppression of the ERK pathway, suggesting that baicalein
      is a potential therapeutic agent for HCC. 

PMID- 24039824
TI  - Desiccation induces accumulations of antheraxanthin and zeaxanthin in intertidal
      macro-alga Ulva pertusa (Chlorophyta).
AB  - For plants and algae, exposure to high light levels is deleterious to their
      photosynthetic machineries. It also can accelerate water evaporation and thus
      potentially lead to drought stress. Most photosynthetic organisms protect
      themselves against high light caused photodamages by xanthophyll cycle-dependent
      thermal energy dissipation. It is generally accepted that high light activates
      xanthophyll cycle. However, the relationship between xanthophyll cycle and
      drought stress remains ambiguous. Herein, Ulva pertusa (Chlorophyta), a
      representative perennial intertidal macro-algae species with high drought
      tolerant capabilities and simple structures, was used to investigate the
      operation of xanthophyll cycle during desiccation in air. The results indicate
      that desiccation under dim light induced accumulation of antheraxanthin (Ax) and
      zeaxanthin (Zx) at the expense of violaxanthin (Vx). This accumulation could be
      arrested by dithiothreitol completely and by uncoupler (carbonyl cyanide p
      trifluoromethoxyphenylhydrazone) partially, implying the participation of Vx de
      epoxidase in conversion of Vx to Ax and Zx. Treatment with inhibitors of electron
      transport along thylakoid membrane, e.g. DCMU, PG and DBMIB, did not
      significantly arrest desiccation-induced accumulation of Ax and Zx. We propose
      that for U. pertusa, besides excess light, desiccation itself could also induce
      accumulation of Ax and Zx. This accumulation could proceed without electron
      transport along thylakoid membrane, and is possibly resulting from the reduction
      of thylakoid lumen volume during desiccation. Considering the pleiotropic effects
      of Ax and Zx, accumulated Ax and Zx may function in protecting thylakoid membrane
      and enhancing thermal quenching during emersion in air. 

PMID- 24039825
TI  - Chronology of Ksar Akil (Lebanon) and implications for the colonization of Europe
      by anatomically modern humans.
AB  - The Out-of-Africa model holds that anatomically modern humans (AMH) evolved and
      dispersed from Africa into Asia, and later Europe. Palaeoanthropological evidence
      from the Near East assumes great importance, but AMH remains from the region are
      extremely scarce. 'Egbert', a now-lost AMH fossil from the key site of Ksar Akil
      (Lebanon) and 'Ethelruda', a recently re-discovered fragmentary maxilla from the
      same site, are two rare examples where human fossils are directly linked with
      early Upper Palaeolithic archaeological assemblages. Here we radiocarbon date the
      contexts from which Egbert and Ethelruda were recovered, as well as the levels
      above and below the findspots. In the absence of well-preserved organic
      materials, we primarily used marine shell beads, often regarded as indicative of
      behavioural modernity. Bayesian modelling allows for the construction of a
      chronostratigraphic framework for Ksar Akil, which supports several conclusions.
      The model-generated age estimates place Egbert between 40.8-39.2 ka cal BP (68.2%
      prob.) and Ethelruda between 42.4-41.7 ka cal BP (68.2% prob.). This indicates
      that Egbert is of an age comparable to that of the oldest directly-dated European
      AMH (Pestera cu Oase). Ethelruda is older, but on current estimates not older
      than the modern human teeth from Cavallo in Italy. The dating of the so-called
      "transitional" or Initial Upper Palaeolithic layers of the site may indicate that
      the passage from the Middle to Upper Palaeolithic at Ksar Akil, and possibly in
      the wider northern Levant, occurred later than previously estimated, casting some
      doubts on the assumed singular role of the region as a locus for human dispersals
      into Europe. Finally, tentative interpretations of the fossil's taxonomy,
      combined with the chronometric dating of Ethelruda's context, provides evidence
      that the transitional/IUP industries of Europe and the Levant, or at least some
      of them, may be the result of early modern human migration(s). 

PMID- 24039826
TI  - Metabolic changes in summer active and anuric hibernating free-ranging brown
      bears (Ursus arctos).
AB  - The brown bear (Ursus arctos) hibernates for 5 to 6 months each winter and during
      this time ingests no food or water and remains anuric and inactive. Despite these
      extreme conditions, bears do not develop azotemia and preserve their muscle and
      bone strength. To date most renal studies have been limited to small numbers of
      bears, often in captive environments. Sixteen free-ranging bears were darted and
      had blood drawn both during hibernation in winter and summer. Samples were
      collected for measurement of creatinine and urea, markers of inflammation, the
      calcium-phosphate axis, and nutritional parameters including amino acids. In
      winter the bear serum creatinine increased 2.5 fold despite a 2-fold decrease in
      urea, indicating a remarkable ability to recycle urea nitrogen during
      hibernation. During hibernation serum calcium remained constant despite a
      decrease in serum phosphate and a rise in FGF23 levels. Despite prolonged
      inactivity and reduced renal function, inflammation does not ensue and bears seem
      to have enhanced antioxidant defense mechanisms during hibernation. Nutrition
      parameters showed high fat stores, preserved amino acids and mild hyperglycemia
      during hibernation. While total, essential, non-essential and branched chain
      amino acids concentrations do not change during hibernation anorexia, changes in
      individual amino acids ornithine, citrulline and arginine indicate an active,
      although reduced urea cycle and nitrogen recycling to proteins. Serum uric acid
      and serum fructose levels were elevated in summer and changes between seasons
      were positively correlated. Further studies to understand how bears can prevent
      the development of uremia despite minimal renal function during hibernation could
      provide new therapeutic avenues for the treatment of human kidney disease. 

PMID- 24039827
TI  - Social and population structure in the ant Cataglyphis emmae.
AB  - Dispersal has consequences not only for individual fitness, but also for
      population dynamics, population genetics and species distribution. Social
      Hymenoptera show two contrasting colony reproductive strategies, dependent and
      independent colony foundation modes, and these are often associated to the
      population structures derived from inter and intra-population gene flow processes
      conditioned by alternative dispersal strategies. Here we employ microsatellite
      and mitochondrial markers to investigate the population and social genetic
      structure and dispersal patterns in the ant Cataglyphis emmae at both, local and
      regional scales. We find that C. emmae is monogynous and polyandrous. Lack of
      detection of any population viscosity and population structure with nuclear
      markers at the local scale suggests efficient dispersal, in agreement with a lack
      of inbreeding. Contrasting demographic differences before and during the mating
      seasons suggest that C. emmae workers raise sexuals in peripheric nest chambers
      to reduce intracolonial conflicts. The high genetic differentiation recovered
      from the mtDNA haplotypes, together with the significant correlation of such to
      geographic distance, and presence of new nuclear alleles between areas (valleys)
      suggest long-term historical isolation between these regions, indicative of
      limited dispersal at the regional scale. Our findings on the ecological, social
      and population structure of this species increases our understanding of the
      patterns and processes involved under independent colony foundation. 

PMID- 24039828
TI  - Low intensity and frequency pulsed electromagnetic fields selectively impair
      breast cancer cell viability.
AB  - INTRODUCTION: A common drawback of many anticancer therapies is non-specificity
      in action of killing. We investigated the potential of ultra-low intensity and
      frequency pulsed electromagnetic fields (PEMFs) to kill breast cancer cells. Our
      criteria to accept this technology as a potentially valid therapeutic approach
      were: 1) cytotoxicity to breast cancer cells and; 2) that the designed fields
      proved innocuous to healthy cell classes that would be exposed to the PEMFs
      during clinical treatment. METHODS: MCF7 breast cancer cells and their normal
      counterparts, MCF10 cells, were exposed to PEMFs and cytotoxic indices measured
      in order to design PEMF paradigms that best kill breast cancer cells. The PEMF
      parameters tested were: 1) frequencies ranging from 20 to 50 Hz; 2) intensities
      ranging from 2 mT to 5 mT and; 3) exposure durations ranging from 30 to 90
      minutes per day for up to three days to determine the optimum parameters for
      selective cancer cell killing. RESULTS: We observed a discrete window of
      vulnerability of MCF7 cells to PEMFs of 20 Hz frequency, 3 mT magnitude and
      exposure duration of 60 minutes per day. The cell damage accrued in response to
      PEMFs increased with time and gained significance after three days of consecutive
      daily exposure. By contrast, the PEMFs parameters determined to be most cytotoxic
      to breast cancer MCF-7 cells were not damaging to normal MCF-10 cells.
      CONCLUSION: Based on our data it appears that PEMF-based anticancer strategies
      may represent a new therapeutic approach to treat breast cancer without affecting
      normal tissues in a manner that is non-invasive and can be potentially combined
      with existing anti-cancer treatments.

PMID- 24039829
TI  - Potential cost saving of Epoetin alfa in elective hip or knee surgery due to
      reduction in blood transfusions and their side effects: a discrete-event
      simulation model.
AB  - OBJECTIVES: Transfusion of allogeneic blood is still common in orthopedic
      surgery. This analysis evaluates from the perspective of a German hospital the
      potential cost savings of Epoetin alfa (EPO) compared to predonated autologous
      blood transfusions or to a nobloodconservationstrategy (allogeneic blood
      transfusion strategy)during elective hip and knee replacement surgery. METHODS:
      Individual patients (N = 50,000) were simulated based on data from controlled
      trials, the German DRG institute (InEK) and various publications and entered into
      a stochastic model (Monte-Carlo) of three treatment arms: EPO, preoperative
      autologous donation and nobloodconservationstrategy. All three strategies lead to
      a different risk for an allogeneic blood transfusion. The model focused on the
      costs and events of the three different procedures. The costs were obtained from
      clinical trial databases, the German DRG system, patient records and medical
      publications: transfusion (allogeneic red blood cells: ?320/unit and autologous
      red blood cells: ?250/unit), pneumonia treatment (?5,000), and length of stay
      (?300/day). Probabilistic sensitivity analyses were performed to determine which
      factors had an influence on the model's clinical and cost outcomes. RESULTS: At
      acquisition costs of ?200/40,000 IU EPO is cost saving compared to autologous
      blood donation, and cost-effective compared to a nobloodconservationstrategy. The
      results were most sensitive to the cost of EPO, blood units and hospital days.
      CONCLUSIONS: EPO might become an attractive blood conservation strategy for
      anemic patients at reasonable costs due to the reduction in allogeneic blood
      transfusions, in the modeled incidence of transfusion-associated pneumonia andthe
      prolongedlength of stay.

PMID- 24039830
TI  - Altitudinal gradient of microbial biomass phosphorus and its relationship with
      microbial biomass carbon, nitrogen, and rhizosphere soil phosphorus on the
      eastern slope of Gongga Mountain, SW China.
AB  - Microbial biomass phosphorus (MBP) is one of the most active forms of phosphorus
      (P) in soils. MBP plays an important role in the biogeochemical P cycle. To
      explore MBP distribution and its relationship with other factors, the MBP and
      rhizosphere soil P concentrations and fractions in six vegetation zones on the
      eastern slope of Gongga Mountain in SW China were investigated. The MBP
      distribution followed a parabolic pattern with altitude and the concentration was
      highest in the subalpine dark coniferous forest (SDC) zone, which was
      approximately 3500 m above sea level (asl). Below 3500 m asl, the MBP
      distribution was controlled by precipitation and vegetation type. In addition,
      temperature, precipitation and vegetation type controlled the MBP distribution at
      elevations above 3500 m asl. No specific distribution pattern was determined
      regarding rhizosphere soil P fractions. However, MBP was significantly correlated
      with the unavailable P fraction in the rhizosphere rather than with the available
      P fraction. This result suggests that the relationships between the rhizosphere
      soil P fractions and the MBP depend on time. The microbial biomass element ratios
      were relatively consistent on the eastern slope of Gongga Mountain. However,
      variations in the microbial biomass element rations were observed in six of the
      vegetation zones. The mean C:N:P ratio was 9.0?1.3?1. Overall, vegetation type
      resulted in the observed fluctuations of the microbial biomass element ratio. 

PMID- 24039831
TI  - Alpha cyano-4-hydroxy-3-methoxycinnamic acid inhibits proliferation and induces
      apoptosis in human breast cancer cells.
AB  - This study investigated the underlying mechanism of 4-hydroxy-3-methoxycinnamic
      acid (ACCA), on the growth of breast cancer cells and normal immortal epithelial
      cells, and compared their cytotoxic effects responses. Treatment of breast cancer
      cells (MCF-7, T47D, and MDA-231) with ACCA resulted in dose- and time-dependent
      decrease of cell proliferation, viability in colony formation assay, and
      programmed cell death (apoptosis) with minimal effects on non-tumoral cells. The
      ability of ACCA to suppress growth in cancer cells not expressing or containing
      defects in p53 gene indicates a lack of involvement of this critical tumor
      suppressor element in mediating ACCA-induced growth inhibition. Induction of
      apoptosis correlated with an increase in Bax protein, an established inducer of
      programmed cell death, and the ratio of Bax to Bcl-2, an established inhibitor of
      apoptosis. We also documented the ability of ACCA to inhibit the migration and
      invasion of MDA-231 cells with ACCA in vitro. Additionally, tumor growth of MDA
      231 breast cancer cells in vivo was dramatically affected with ACCA. On the basis
      of its selective anticancer inhibitory activity on tumor cells, ACCA may
      represent a promising therapeutic drug that should be further evaluated as a
      chemotherapeutic agent for human breast cancer. 

PMID- 24039832
TI  - EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small
      cell lung cancer.
AB  - Activating epidermal growth factor receptor (EGFR) mutations are recognized
      biomarkers for patients with metastatic non-small cell lung cancer (NSCLC)
      treated with EGFR tyrosine kinase inhibitors (TKIs). EGFR TKIs can also have
      activity against NSCLC without EGFR mutations, requiring the identification of
      additional relevant biomarkers. Previous studies on tumor EGFR protein levels and
      EGFR gene copy number revealed inconsistent results. The aim of the study was to
      identify novel biomarkers of the response to TKIs in NSCLC by investigating whole
      genome expression at the exon-level. We used exon arrays and clinical samples
      from a previous trial (SAKK19/05) to investigate the expression variations at the
      exon-level of 3 genes potentially playing a key role in modulating treatment
      response: EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and
      vascular endothelial growth factor (VEGFA). We identified the expression of EGFR
      exon 18 as a new predictive marker for patients with untreated metastatic NSCLC
      treated with bevacizumab and erlotinib in the first line setting. The
      overexpression of EGFR exon 18 in tumor was significantly associated with tumor
      shrinkage, independently of EGFR mutation status. A similar significant
      association could be found in blood samples. In conclusion, exonic EGFR
      expression particularly in exon 18 was found to be a relevant predictive
      biomarker for response to bevacizumab and erlotinib. Based on these results, we
      propose a new model of EGFR testing in tumor and blood. 

PMID- 24039833
TI  - SPAK deficiency corrects pseudohypoaldosteronism II caused by WNK4 mutation.
AB  - Stimulation of the OSR1 (Oxidative stress-responsive kinase-1)/SPAK [STE20
      (sterile 20)/SPS1-related proline/alanine-rich kinase]-NCC (Na(+)-Cl(-)
      cotransporter) signaling cascade plays an important role in the WNK [With-No
      Lysine (K)] kinase 4 D561A knock-in mouse model of pseudohypoaldosteronism type
      II (PHA II) characterized by salt-sensitive hypertension and hyperkalemia. The
      aim of this study was to investigate the respective roles of Osr1 and Spak in the
      pathogenesis of PHA II in vivo. Wnk4 (D561A/+) mice were crossed with kidney
      tubule-specific (KSP) Osr1 knockout (KSP-Osr1 (-/-)) and Spak knockout (Spak (-/
      )) mice. Blood pressure, plasma and urine biochemistries, and the relevant
      protein expression in the kidneys were examined. Wnk4 (D561A/+), KSP-Osr1 (-/-),
      and Spak (-/-) mice recapitulated the phenotypes of PHA II, Bartter-like
      syndrome, and Gitelman syndrome, respectively. Wnk4 (D561A/+).KSP-Osr1 (-/-)
      remained phenotypically PHA II while Wnk4 (D561A/+).Spak (-/-) mice became
      normotensive and lacked the PHA II phenotype. Phosphorylated Spak and Ncc were
      similarly increased in both Wnk4 (D561A/+) and Wnk4 (D561A/+).KSP-Osr1 (-/-) mice
      while phosphorylated Ncc normalized in Wnk4 (D561A/+).Spak (-/-) mice.
      Furthermore, Wnk4 (D561A/+).KSP-Osr1 (-/-) mice exhibited exaggerated salt
      excretion in response to thiazide diuretics while Wnk4 (D561A/+).Spak (-/-) mice
      exhibited normal responses. Wnk4(D561A/+).Spak (-/-).KSP-Osr1 (-/-) triple mutant
      mice had low blood pressure and diminished phosphorylated Ncc. Both SPAK and OSR1
      are important in the maintenance of blood pressure but activation of SPAK-NCC
      plays the dominant role in PHA II. SPAK may be a therapeutic target for disorders
      with salt-sensitive hypertension related to WNK4 activation. 

PMID- 24039834
TI  - Enhancement of differentiation and mineralisation of osteoblast-like cells by
      degenerate electrical waveform in an in vitro electrical stimulation model
      compared to capacitive coupling.
AB  - Electrical stimulation (ES) is effective in enhancing bone healing, however the
      best electrical waveform, mode of application and mechanisms remains unclear. We
      recently reported the in vitro differential healing response of a novel
      electrical waveform called degenerate sine wave (DW) compared to other forms of
      ES. This study further explores this original observation on osteoblast cells.
      Here, we electrically stimulated SaOS-2 osteoblast-like cells with DW in an in
      vitro ES chamber (referred to as 'DW stimulation') and compared the intracellular
      effects to capacitive coupling (CC) stimulation. ES lasted for 4 h, followed by
      an incubation period of 20 h and subsequent ES for 4 additional hours.
      Cytotoxicity, proliferation, differentiation and mineralisation of the osteoblast
      like cells were evaluated to determine the cell maturation process. DW
      significantly enhanced the differentiation of cells when compared to CC
      stimulation with increased alkaline phosphatase and collagen I gene expression by
      quantitative real time- polymerase chain reaction analysis (p<0.01). Moreover, DW
      significantly increased the mineralisation of cells compared to CC stimulation.
      Furthermore the transcription of osteocalcin, osteonectin, osteopontin and bone
      sialoprotein (p<0.05) was also up regulated by DW. However, ES did not augment
      the proliferation of cells. Translational analysis by immunocytochemistry and
      Western blotting showed increased collagen I, osteocalcin and osteonectin
      expression after DW than CC stimulation. In summary, we have demonstrated for the
      first time that DW stimulation in an in vitro ES chamber has a significant effect
      on maturation of osteoblast-like cells compared to CC stimulation of the same
      magnitude. 

PMID- 24039835
TI  - Ethnic differences in body mass index trajectories from adolescence to adulthood:
      a focus on Hispanic and Asian subgroups in the United States.
AB  - BACKGROUND: Compared to whites, U.S. Hispanics have higher obesity rates; U.S.
      Asians have lower rates. However Hispanics and Asians are each comprised of
      several ethnic subgroups that differ with respect to country of origin,
      immigration history, and geographic distribution across the U.S. Among
      adolescents, ethnic differences in obesity have been previously reported, but no
      studies have examined longitudinal change in body mass index (BMI) by Hispanic
      and Asian subgroup category to understand when and why these disparities emerge,
      especially during the critical transition between adolescence and adulthood.
      METHODS: Using nationally-representative, longitudinal data from 1355 Hispanics
      (Mexican, Puerto Rican, Cuban, Central/South American, Other Hispanic), 520
      Asians (Chinese, Filipino, Other Asian), and 5061whites from the National
      Longitudinal Study of Adolescent Health (Waves II-IV: 1996-2009), we used linear
      mixed spline models to examine whether Hispanic and Asian adolescent subgroups
      shared the same BMI trajectories as whites as they aged into adulthood. We also
      investigated the role of social and behavioral factors in explaining race/ethnic
      differences. RESULTS: Among Hispanics, Mexican and Puerto Rican-origin
      individuals exhibited faster increases in BMI both in adolescence and in
      adulthood and these patterns were not attributable to the measured social and
      behavioral factors. There was also evidence of emerging disparities in Cuban
      males, and in Central/South Americans relative to whites. In contrast, Chinese,
      Filipino, and Other Asian adolescents had significantly lower BMI and slower BMI
      increases in adulthood compared to whites. In models adjusted for social and
      behavioral factors, Chinese-white and Other Asian-white differentials remained
      unexplained. CONCLUSIONS: Aggregate estimates of Hispanics and Asians mask
      important heterogeneity in BMI. A better understanding of weight dynamics early
      in the life course can inform how and when disparities emerge to better target
      prevention efforts.

PMID- 24039837
TI  - Surface display of recombinant Drosophila melanogaster acetylcholinesterase for
      detection of organic phosphorus and carbamate pesticides.
AB  - Acetylcholinesterase (AChE) is commonly used for the detection of organophosphate
      (OP) and carbamate (CB) insecticides. However, the cost of this commercially
      available enzyme is high, making high-throughput insecticide detection
      improbable. In this study we constructed a new AChE yeast expression system in
      Saccharomyces cerevisiae for the expression of a highly reactive recombinant AChE
      originating from Drosophila melanogaster (DmAChE). Specifically, the coding
      sequence of DmAChE was fused with the 3'-terminal half of an alpha-agglutinin
      anchor region, along with an antigen tag for the detection of the recombinant
      protein. The target sequence was cloned into the yeast expression vector pYes
      DEST52, and the signal peptide sequence was replaced with a glucoamylase
      secretion region for induced expression. The resultant engineered vector was
      transformed into S. cerevisiae. DmAChE was expressed and displayed on the cell
      surface after galactose induction. Our results showed that the recombinant
      protein displayed activity comparable to the commercial enzyme. We also detected
      different types of OP and CB insecticides through enzyme inhibition assays, with
      the expressed DmAChE showing high sensitivity. These results show the
      construction of a new yeast expression system for DmAChE, which can subsequently
      be used for detecting OP and CB insecticides with reduced economic costs. 

PMID- 24039836
TI  - Downregulation of miR-151-5p contributes to increased susceptibility to
      arrhythmogenesis during myocardial infarction with estrogen deprivation.
AB  - Estrogen deficiency is associated with increased incidence of cardiovascular
      diseases. But merely estrogen supplementary treatment can induce many severe
      complications such as breast cancer. The present study was designed to elucidate
      molecular mechanisms underlying increased susceptibility of arrhythmogenesis
      during myocardial infarction with estrogen deprivation, which provides us a new
      target to cure cardiac disease accompanied with estrogen deprivation. We
      successfully established a rat model of myocardial ischemia (MI) accompanied with
      estrogen deprivation by coronary artery ligation and ovariectomy (OVX).
      Vulnerability and mortality of ventricular arrhythmias increased in estrogen
      deficiency rats compared to non estrogen deficiency rats when suffered MI, which
      was associated with down-regulation of microRNA-151-5p (miR-151-5p). Luciferase
      Reporter Assay demonstrated that miR-151-5p can bind to the 3'-UTR of FXYD1
      (coding gene of phospholemman, PLM) and inhibit its expression. We found that the
      expression of PLM was increased in (OVX+MI) group compared with MI group. More
      changes such as down-regulation of Kir2.1/IK1, calcium overload had emerged in
      (OVX+MI) group compared to MI group merely. Transfection of miR-151-5p into
      primary cultured myocytes decreased PLM levels and [Ca(2+)]i, however, increased
      Kir2.1 levels. These effects were abolished by the antisense oligonucleotides
      against miR-151-5p. Co-immunoprecipitation and immunofluorescent experiments
      confirmed the co-localization between Kir2.1 and PLM in rat ventricular tissue.
      We conclude that the increased ventricular arrhythmias vulnerability in response
      to acute myocardial ischemia in rat is critically dependent upon down-regulation
      of miR-151-5p. These findings support the proposal that miR-151-5p could be a
      potential therapeutic target for the prevention of ischemic arrhythmias in the
      subjects with estrogen deficiency. 

PMID- 24039838
TI  - Impact of single and stacked insect-resistant Bt-cotton on the honey bee and
      silkworm.
AB  - Transgenic insect-resistant cotton (Bt cotton) has been extensively planted in
      China, but its effects on non-targeted insect species such as the economically
      important honey bee (Apis mellifera) and silkworm (Bombyx mori) currently are
      unknown. In this study, pollen from two Bt cotton cultivars, one expressing
      Cry1Ac/EPSPS and the other expressing Cry1Ac/Cry2Ab, were used to evaluate the
      effects of Bt cotton on adult honey bees and silkworm larvae. Laboratory feeding
      studies showed no adverse effects on the survival, cumulative consumption, and
      total hemocyte count (THC) of A. mellifera fed with Bt pollen for 7 days. No
      effects on the survival or development of B. mori larvae were observed either. A
      marginally significant difference between Cry1Ac/Cry2Ab cotton and the
      conventional cotton on the THC of the 3(rd) day of 5(th) B. mori instar larvae
      was observed only at the two highest pollen densities (approximately 900 and 8000
      grains/cm(2)), which are much higher than the pollen deposition that occurs under
      normal field conditions. The results of this study show that pollen of the tested
      Bt cotton varieties carried no lethal or sublethal risk for A. mellifera, and the
      risk for B. mori was negligible. 

PMID- 24039839
TI  - Protective role of Spirulina platensis against acute deltamethrin-induced
      toxicity in rats.
AB  - Deltamethrin is a broad-spectrum synthetic pyrethroid insecticide and acaricide
      widely used for agricultural and veterinary purposes. However, its human and
      animal exposure leads to hepatonephrotoxicity. Therefore, the present study was
      undertaken to examine the hepatonephroprotective and antioxidant potential of
      Spirulina platensis against deltamethrin toxicity in male Wistar albino rats.
      Deltamethrin treated animals revealed a significant increase in serum biochemical
      parameters as well as hepatic and renal lipid peroxidation but caused an
      inhibition in antioxidant biomarkers. Spirulina normalized the elevated serum
      levels of AST, ALT, APL, uric acid, urea and creatinine. Furthermore, it reduced
      deltamethrin-induced lipid peroxidation and oxidative stress in a dose dependent
      manner. Therefore, it could be concluded that spirulina administration able to
      minimize the toxic effects of deltamethrin by its free radical-scavenging and
      potent antioxidant activity. 

PMID- 24039840
TI  - Integrin - dependent mechanotransduction in mechanically stimulated human annulus
      fibrosus cells: evidence for an alternative mechanotransduction pathway operating
      with degeneration.
AB  - Intervertebral disc (IVD) cells derived from degenerate tissue respond aberrantly
      to mechanical stimuli, potentially due to altered mechanotransduction pathways.
      Elucidation of the altered, or alternative, mechanotransduction pathways
      operating with degeneration could yield novel targets for the treatment of IVD
      disease. Our aim here was to investigate the involvement of RGD-recognising
      integrins and associated signalling molecules in the response to cyclic tensile
      strain (CTS) of human annulus fibrosus (AF) cells derived from non-degenerate and
      degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were
      cyclically strained with and without function blocking RGD - peptides with 10%
      strain, 1.0 Hz for 20 minutes using a Flexercell(r) strain device. QRT-PCR and
      Western blotting were performed to analyse gene expression of type I collagen and
      ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK), respectively. The
      response to 1.0 Hz CTS differed between the two groups of AF cells, with
      decreased ADAMTS -4 gene expression and decreased type I collagen gene expression
      post load in AF cells derived from non-degenerate and degenerate IVDs,
      respectively. Pre-treatment of non-degenerate AF cells with RGD peptides
      prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an
      increase in expression at 24 hours, a response not observed in degenerate AF
      cells where RGD pre-treatment failed to inhibit the mechano-response. In
      addition, FAK phosphorylation increased in CTS stimulated AF cells derived from
      non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the
      CTS - dependent increase in phosphorylated FAK. Our findings suggest that RGD 
      integrins are involved in the 1.0 Hz CTS - induced mechano-response observed in
      AF cells derived from non-degenerate, but not degenerate IVDs. This data supports
      our previous work, suggesting an alternative mechanotransduction pathway may be
      operating in degenerate AF cells. 

PMID- 24039841
TI  - Estradiol and tamoxifen induce cell migration through GPR30 and activation of
      focal adhesion kinase (FAK) in endometrial cancers with low or without nuclear
      estrogen receptor alpha (ERalpha).
AB  - Estrogens and tamoxifen (an antiestrogen) exert their actions by activation of
      estrogen receptor (ER) through genomic and non-genomic mechanisms and are
      implicated in the development of endometrial cancer. Previous reports have
      demonstrated that estradiol and tamoxifen induce proliferation of human
      endometrial cancer cells through GPR30 (non-genomic ER) signaling pathway.
      Herein, we demonstrate that phosphorylation of focal adhesion kinase (FAK) is
      involved in cell migration induced by estradiol, tamoxifen and G1 (a GPR30
      agonist) through the transmembrane ER (GPR30) in endometrial cancer cell lines
      with or without ERalpha (Ishikawa and RL95-2). Additionally, the GPR30-mediated
      cell migration was further abolished by administration of either specific RNA
      interference targeting GPR30 or an FAK inhibitor. Moreover, we have validated
      that the signaling between GPR30 and phosphorylated FAK is indeed mediated by the
      EGFR/PI3K/ERK pathway. Clinically, a significant correlation between levels of
      GPR30 and phophorylated FAK (pFAK) observed in human endometrial cancer tissues
      with low or without ERalpha further suggested that estrogen-induced
      phosphorylation of FAK and cell migration were most likely triggered by GPR30
      activation. These results provided new insights for understanding the
      pathophysiological functions of GPR30 in human endometrial cancers. 

PMID- 24039843
TI  - The genetic history of indigenous populations of the Peruvian and Bolivian
      Altiplano: the legacy of the Uros.
AB  - The Altiplano region of the South American Andes is marked by an inhospitable
      climate to which the autochthonous human populations adapted and then developed
      great ancient civilizations, such as the Tiwanaku culture and the Inca Empire.
      Since pre-Columbian times, different rulers established themselves around the
      Titicaca and Poopo Lakes. By the time of the arrival of Spaniards, Aymara and
      Quechua languages were predominant on the Altiplano under the rule of the Incas,
      although the occurrence of other spoken languages, such as Puquina and Uruquilla,
      suggests the existence of different ethnic groups in this region. In this study,
      we focused on the pre-Columbian history of the autochthonous Altiplano
      populations, particularly the Uros ethnic group, which claims to directly descend
      from the first settlers of the Andes, and some linguists suggest they might
      otherwise be related to Arawak speaking groups from the Amazon. Using
      phylogeographic, population structure and spatial genetic analyses of Y
      chromosome and mtDNA data, we inferred the genetic relationships among Uros
      populations (Los Uros from Peru, Uru-Chipaya and Uru-Poopo from Bolivia), and
      compared their haplotype profiles with eight Aymara, nine Quechua and two Arawak
      (Machiguenga and Yanesha) speaking populations from Peru and Bolivia. Our results
      indicated that Uros populations stand out among the Altiplano populations, while
      appearing more closely related to the Aymara and Quechua from Lake Titicaca and
      surrounding regions than to the Amazon Arawaks. Moreover, the Uros populations
      from Peru and Bolivia are genetically differentiated from each other, indicating
      a high heterogeneity in this ethnic group. Finally, our results support the
      distinctive ancestry for the Uros populations of Peru and Bolivia, which are
      likely derived from ancient Andean lineages that were partially replaced during
      more recent farming expansion events and the establishment of complex
      civilizations in the Andes. 

PMID- 24039842
TI  - Cyanidin-3-glucoside suppresses cytokine-induced inflammatory response in human
      intestinal cells: comparison with 5-aminosalicylic acid.
AB  - The potential use of polyphenols in the prevention and treatment of chronic
      inflammatory diseases has been extensively investigated although the mechanisms
      involved in cellular signaling need to be further elucidated. Cyanidin-3
      glucoside is a typical anthocyanin of many pigmented fruits and vegetables
      widespread in the human diet. In the present study, the protection afforded by
      cyanidin-3-glucoside against cytokine-triggered inflammatory response was
      evaluated in the human intestinal HT-29 cell line, in comparison with 5
      aminosalicylic acid, a well-established anti-inflammatory drug, used in
      inflammatory bowel disease. For this purpose, some key inflammatory mediators and
      inflammatory enzymes were examined. Our data showed that cyanidin-3-glucoside
      reduced cytokine-induced inflammation in intestinal cells, in terms of NO, PGE2
      and IL-8 production and of iNOS and COX-2 expressions, at a much lower
      concentration than 5-aminosalicylic acid, suggesting a higher anti-inflammatory
      efficiency. Interestingly, cyanidin-3-glucoside and 5-aminosalicylic acid neither
      prevented IkB-alpha degradation nor the activation of NF-kB, but significantly
      reduced cytokine-induced levels of activated STAT1 accumulated in the cell
      nucleus. In addition, we established that phosphorylated p38 MAPK was not
      involved in the protective effect of cyanidin-3-glucoside or 5-aminosalicylic
      acid. Taking into account the high concentrations of dietary anthocyanins
      potentially reached in the gastrointestinal tract, cyanidin-3-glucoside may be
      envisaged as a promising nutraceutical giving complementary benefits in the
      context of inflammatory bowel disease. 

PMID- 24039844
TI  - Calling in the cold: pervasive acoustic presence of humpback whales (Megaptera
      novaeangliae) in Antarctic coastal waters.
AB  - Humpback whales migrate between relatively unproductive tropical or temperate
      breeding grounds and productive high latitude feeding areas. However, not all
      individuals of a population undertake the annual migration to the breeding
      grounds; instead some are thought to remain on the feeding grounds year-round,
      presumably to avoid the energetic demands of migration. In the Southern
      Hemisphere, ice and inclement weather conditions restrict investigations of
      humpback whale presence on feeding grounds as well as the extent of their
      southern range. Two years of near-continuous recordings from the PerenniAL
      Acoustic Observatory in the Antarctic Ocean (PALAOA, Ekstrom Iceshelf, 70 degrees
      31'S, 8 degrees 13'W) are used to explore the acoustic presence of humpback
      whales in an Antarctic coastal area. Humpback whale calls were present during
      nine and eleven months of 2008 and 2009, respectively. In 2008, calls were
      present in January through April, June through August, November and December,
      whereas in 2009, calls were present throughout the year, except in September.
      Calls occurred in un-patterned sequences, representing non-song sound production.
      Typically, calls occurred in bouts, ranging from 2 to 42 consecutive days with
      February, March and April having the highest daily occurrence of calls in 2008.
      In 2009, February, March, April and May had the highest daily occurrence of
      calls. Whales were estimated to be within a 100 km radius off PALAOA. Calls were
      also present during austral winter when ice cover within this radius was >90%.
      These results demonstrate that coastal areas near the Antarctic continent are
      likely of greater importance to humpback whales than previously assumed,
      presumably providing food resources year-round and open water in winter where
      animals can breathe. 

PMID- 24039845
TI  - People's perceptions about the importance of forests on Borneo.
AB  - We ascertained villagers' perceptions about the importance of forests for their
      livelihoods and health through 1,837 reliably answered interviews of mostly male
      respondents from 185 villages in Indonesian and Malaysian Borneo. Variation in
      these perceptions related to several environmental and social variables, as shown
      in classification and regression analyses. Overall patterns indicated that forest
      use and cultural values are highest among people on Borneo who live close to
      remaining forest, and especially among older Christian residents. Support for
      forest clearing depended strongly on the scale at which deforestation occurs.
      Deforestation for small-scale agriculture was generally considered to be positive
      because it directly benefits people's welfare. Large-scale deforestation (e.g.,
      for industrial oil palm or acacia plantations), on the other hand, appeared to be
      more context-dependent, with most respondents considering it to have overall
      negative impacts on them, but with people in some areas considering the benefits
      to outweigh the costs. The interviews indicated high awareness of negative
      environmental impacts of deforestation, with high levels of concern over higher
      temperatures, air pollution and loss of clean water sources. Our study is unique
      in its geographic and trans-national scale. Our findings enable the development
      of maps of forest use and perceptions that could inform land use planning at a
      range of scales. Incorporating perspectives such as these could significantly
      reduce conflict over forest resources and ultimately result in more equitable
      development processes. 

PMID- 24039846
TI  - Expression, tissue distribution and function of miR-21 in esophageal squamous
      cell carcinoma.
AB  - OBJECTIVE: MiR-21 is an oncomir expressed by malignant cells and/or tumor
      microenvironment components. In this study we focused on understanding the
      effects of stromal miR-21 on esophageal malignant cells. DESIGN: MiR-21
      expression was evaluated in formalin-fixed paraffin-embedded samples from
      patients with esophageal squamous-cell carcinoma (SCC) by quantitative RT-PCR.
      MiR-21 tissue distribution was visualized with in situ hybridization. A co
      culture system of normal fibroblasts and esophageal cancer cells was used to
      determine the effects of fibroblasts on miR-21 expression levels, and on SCC cell
      migration and invasion. RESULTS: MiR-21 was overexpressed in SCCs, when compared
      to the adjacent non-tumor tissues (P = 0.0007), and was mainly localized in the
      cytoplasm of stromal cells adjacent to malignant cells. Accordingly, miR-21
      expression was increased in tumors with high versus low stromal content (P =
      0.04). When co-cultured with normal fibroblasts, miR-21 expression was elevated
      in SCC cells (KYSE-30), while its expression was restricted to fibroblasts when
      co-cultured with adenocarcinoma cells (OE-33 and FLO-1). MiR-21 was detected in
      conditioned media of cancer cell lines, illustrating the release of this miRNA
      into the environment. Co-culturing with normal fibroblasts or addition of
      fibroblast conditioned media caused a significant increase in cell migration and
      invasion potency of KYSE-30 cells (P<0.0001). In addition, co-culturing cancer
      cells with fibroblasts and expression of miR-21 induced the expression of the
      cancer associated fibroblast (CAF) marker S100A4. CONCLUSIONS: MiR-21 expression
      is mostly confined to the SCC stroma and its release from fibroblasts influences
      the migration and invasion capacity of SCC cells. Moreover, miR-21 may be an
      important factor in "activating" fibroblasts to CAFs. These findings provide new
      insights into the role of CAFs and the extracellular matrix in tumor
      microenvironment formation and in tumor cell maintenance, and suggest miR-21 may
      contribute to cellular crosstalk in the tumor microenvironment.

PMID- 24039847
TI  - Patient assessment of chronic illness care, glycemic control and the utilization
      of community health care among the patients with type 2 diabetes in Shanghai,
      China.
AB  - OBJECTIVES: To evaluate the relationship between Patient Assessment of Chronic
      Illness Care in community health centers and self-management behaviors and
      glycemic control and to examine the relationship between Patient Assessment of
      Chronic Illness Care in community health centers and the utilization of community
      health centers for monitoring and treating diabetes among the patients with type
      2 diabetes. METHODS: A questionnaire including self-management behaviors,
      glycemic control, Patient Assessment of Chronic Illness Care in community health
      centers and the most often utilized medical institutions for monitoring and
      treating diabetes (community health centers vs. hospitals) was administered to
      960 patients with type 2 diabetes in Shanghai, China. The relationships between
      Patient Assessment of Chronic Illness Care and self-management behaviors, self
      management behaviors and glycemic control, Patient Assessment of Chronic Illness
      Care and glycemic control, Patient Assessment of Chronic Illness Care and the
      most often utilized medical institutions for monitoring and treating diabetes
      were examined. RESULTS: Wilcoxon rank sum tests showed that the high scores of
      total Patient Assessment of Chronic Illness Care and five subscales in community
      health centers were positively related to almost all the proper self-management
      behaviors and good glycemic control (p<0.05). Almost all of the proper self
      management behaviors were positively related to good glycemic control (p<0.01).
      High summary score of the Patient Assessment of Chronic Illness Care was
      positively associated with the utilization of community health centers for
      monitoring and treating diabetes (p<0.001). CONCLUSIONS: Patient Assessment of
      Chronic Illness Care (implementation of the Chronic Care Model) in community
      health centers was associated with patients' self-management behaviors and
      glycemic control, and finally was associated with the utilization of community
      health centers for monitoring and treating diabetes.

PMID- 24039848
TI  - Downstream signaling pathways in mouse adipose tissues following acute in vivo
      administration of fibroblast growth factor 21.
AB  - FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and
      anti-atherogenic activities in preclinical species. In the current study, we
      investigated the signal transduction pathways downstream of FGF21 following acute
      administration of the growth factor to mice. Focusing on adipose tissues, we
      identified FGF21-mediated downstream signaling events and target engagement
      biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic
      profiling of adipocytes, following FGF21 treatment revealed several specific
      changes in gene expression and post-translational modifications, specifically
      phosphorylation, in several relevant proteins. Affymetrix microarray analysis of
      white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD)
      and db/db mice identified over 150 robust potential RNA transcripts and over 50
      potential secreted proteins that were changed greater than 1.5 fold by FGF21
      acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were
      modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic
      analysis of the combined gene and phosphoprotein profiling data identified a
      number of known metabolic pathways such as glucose uptake, insulin receptor
      signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number
      of novel events with hitherto unknown links to FGF21 signaling were observed at
      both the transcription and protein phosphorylation levels following treatment. We
      conclude that such a combined "omics" approach can be used not only to identify
      robust biomarkers for novel therapeutics but can also enhance our understanding
      of downstream signaling pathways; in the example presented here, novel FGF21
      mediated signaling events in adipose tissue have been revealed that warrant
      further investigation. 

PMID- 24039849
TI  - Label-free detection of Cu(2+) and Hg(2+) ions using reconstructed Cu(2+)
      specific DNAzyme and G-quadruplex DNAzyme.
AB  - Label-free metal ion detection methods were developed. To achieve these, a
      reconstructed Cu(2+)-specific DNA-cleaving DNAzyme (Cu(2+)-specific DNAzyme) with
      an intramolecular stem-loop structure was used. G-quadruplex-forming G-rich
      sequence(s), linked at the ends of double-helix stem of an intramolecular stem
      loop structure, was partly caged in an intramolecular duplex or formed a split G
      quadruplex. Cu(2+)-triggered DNA cleavage at a specific site decreased the
      stability of the double-helix stem, resulting in the formation or destruction of
      G-quadruplex DNAzyme that can effectively catalyze the 2,2'-azinobis(3
      ethylbenzothiazoline)-6-sulfonic acid (ABTS)-H2O2 reaction. Based on these, two
      label-free, cost-effective and simple Cu(2+) sensors were designed. These two
      sensors followed different detection modes: 'turn-on' and 'turn-off'. As for the
      'turn-on' sensor, the intramolecular stem-loop structure ensured a low background
      signal, and the co-amplification of detection signal by dual DNAzymes (Cu(2+)
      specific DNAzyme and G-quadruplex DNAzyme) provided a high sensitivity. This
      sensor enabled the selective detection of aqueous Cu(2+) with a detection limit
      of 3.9 nM. Visual detection was possible. Although the 'turn-off' sensor gave
      lower detection sensitivity than the 'turn-on' one, the characteristics of cost
      effectiveness and ease of operation made it an important implement to reduce the
      possibility of pseudo-positive or pseudo-negative results. Combining the ability
      of Hg(2+) ion to stabilize T-T base mismatch, above dual DNAzymes-based strategy
      was further used for Hg(2+) sensor design. The proposed sensor allowed the
      specific detection of Hg(2+) ion with a detection of 4.8 nM. Visual detection was
      also possible. 

PMID- 24039850
TI  - Quality score based identification and correction of pyrosequencing errors.
AB  - Massively-parallel DNA sequencing using the 454/pyrosequencing platform allows in
      depth probing of diverse sequence populations, such as within an HIV-1 infected
      individual. Analysis of this sequence data, however, remains challenging due to
      the shorter read lengths relative to that obtained by Sanger sequencing as well
      as errors introduced during DNA template amplification and during pyrosequencing.
      The ability to distinguish real variation from pyrosequencing errors with high
      sensitivity and specificity is crucial to interpreting sequence data. We
      introduce a new algorithm, CorQ (Correction through Quality), which utilizes the
      inherent base quality in a sequence-specific context to correct for homopolymer
      and non-homopolymer insertion and deletion (indel) errors. CorQ also takes uneven
      read mapping into account for correcting pyrosequencing miscall errors and it
      identifies and corrects carry forward errors. We tested the ability of CorQ to
      correctly call SNPs on a set of pyrosequences derived from ten viral genomes from
      an HIV-1 infected individual, as well as on six simulated pyrosequencing datasets
      generated using non-zero error rates to emulate errors introduced by PCR. When
      combined with the AmpliconNoise error correction method developed to remove
      ambiguities in signal intensities, we attained a 97% reduction in indel errors, a
      98% reduction in carry forward errors, and >97% specificity of SNP detection.
      When compared to four other error correction methods, AmpliconNoise+CorQ
      performed at equal or higher SNP identification specificity, but the sensitivity
      of SNP detection was consistently higher (>98%) than other methods tested. This
      combined procedure will therefore permit examination of complex genetic
      populations with improved accuracy. 

PMID- 24039851
TI  - Tendon tissue engineering and its role on healing of the experimentally induced
      large tendon defect model in rabbits: a comprehensive in vivo study.
AB  - Healing of large tendon defects is challenging. We studied the role of collagen
      implant with or without polydioxanone (PDS) sheath on the healing of a large
      Achilles tendon defect model, in rabbits. Sixty rabbits were divided into three
      groups. A 2 cm gap was created in the left Achilles tendon of all rabbits. In the
      control lesions, no implant was used. The other two groups were reconstructed by
      collagen and collagen-PDS implants respectively. The animals were clinically
      examined at weekly intervals and their lesions were observed by ultrasonography.
      Blood samples were obtained from the animals and were assessed for hematological
      analysis and determination of serum PDGF level, at 60 days post injury (DPI). The
      animals were then euthanized and their lesions were assessed for gross and
      histopathology, scanning electron microscopy, biomechanical testing, dry matter
      and hydroxyproline content. Another 65 pilot animals were also studied grossly
      and histopathologically to define the host implant interaction and graft
      incorporation at serial time points. The treated animals gained significantly
      better clinical scoring compared to the controls. Treatment with collagen and
      collagen-PDS implants significantly increased the biomechanical properties of the
      lesions compared to the control tendons at 60DPI (P<0.05). The tissue engineered
      implants also reduced peritendinous adhesion, muscle fibrosis and atrophy, and
      increased ultrasonographical echogenicity and homogenicity, maturation and
      differentiation of the collagen fibrils and fibers, tissue alignment and volume
      of the regenerated tissue compared to those of the control lesions (P<0.05). The
      implants were gradually absorbed and substituted by the new tendon. Implantation
      of the bioimplants had a significant role in initiating tendon healing and the
      implants were biocompatible, biodegradable and safe for application in tendon
      reconstructive surgery. The results of the present study may be valuable in
      clinical practice. 

PMID- 24039852
TI  - Distinct ubiquitin binding modes exhibited by SH3 domains: molecular determinants
      and functional implications.
AB  - SH3 domains constitute a new type of ubiquitin-binding domains. We previously
      showed that the third SH3 domain (SH3-C) of CD2AP binds ubiquitin in an
      alternative orientation. We have determined the structure of the complex between
      first CD2AP SH3 domain and ubiquitin and performed a structural and mutational
      analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We
      found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C
      domain does not abrogate ubiquitin binding, in contrast to previous hypothesis
      and our findings for the first two CD2AP SH3 domains. The similar alternative
      binding mode of the SH3-C domains of these related adaptor proteins is
      characterised by a higher affinity to C-terminal extended ubiquitin molecules. We
      conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a
      new ubiquitin-binding mode involved in a different cellular function and thus
      changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono
      ubiquitination. 

PMID- 24039853
TI  - Homocysteine and C-reactive protein associated with progression and prognosis of
      intracranial branch atheromatous disease.
AB  - BACKGROUND AND OBJECTIVES: C-reactive protein (CRP) is a biomarker of
      inflammation and a sensitive predictor of stroke, and high homocysteine (Hcy) is
      also associated with stroke. However, the roles of CRP and Hcy in the
      pathogenesis, progression and prognosis of branch atheromatous disease (BAD) and
      lipohyalinotic degeneration (LD) are largely unknown. We sought to determine the
      relation between them in Chinese patients. METHODS: According to the lesion
      presences shown by diffusion-weighted imaging (DWI), we retrospectively recruited
      a cohort of 308 patients with a diagnosis of BAD and LD from a total of 1458
      consecutive patients with acute ischemic stroke. Progression was defined as
      worsening by > or  = 1-point in the NIHSS for motor function within the first 5
      days. Good outcome was deemed as Modified Rankin Scale (mRS) <= 2 and poor
      outcome was mRS > 2 recorded at one month after onset. RESULTS: This study
      comprised a total of 179 patients with BAD and 129 patients with LD. Subjects in
      patients with LD significantly had an elevated Hcy (p = 0.030), a lower NIHSS
      score on admission (p<0.001) and mRS score at one month after ictus (p<0.001)
      than those in patients with BAD. Elevated Hcy (P = 0.004) and increased CRP (P =
      0.025) were associated with progression in patients with BAD, and CRP (p = 0.006)
      and diabetes mellitus (p = 0.011) were found to be associated with poor outcome
      in patients with BAD. However, no association was observed in patients with LD on
      progression and prognosis. After multivariate logistic regression analysis,
      elevated Hcy (p = 0.002) remained the only independent predictor for the
      progression, and increased CRP (p = 0.027) and smoking (p = 0.012) became the
      independent predictors for the poor outcome in patients with BAD. CONCLUSIONS: In
      patients with BAD, elevated Hcy and increased CRP may independently predict
      progression and prognosis, respectively.

PMID- 24039854
TI  - Bigger is better: characteristics of round gobies forming an invasion front in
      the Danube river.
AB  - Few studies have systematically investigated differences in performance,
      morphology and parasitic load of invaders at different stages of an invasion.
      This study analyzed phenotype-environment correlations in a fish invasion from
      initial absence until establishment in the headwater reach of the second largest
      European river, the Danube. Here, the round goby (Neogobius melanostomus) formed
      73% of the fish abundance and 58% of the fish biomass in rip-rap bank habitats
      after establishment. The time from invasion until establishment was only about
      two years, indicating rapid expansion. Founder populations from the invasion
      front were different from longer established round goby populations in
      demography, morphology, feeding behaviour, sex ratio and parasitic load,
      indicating that plasticity in these traits determines invasion success.
      Competitive ability was mostly dependent on growth/size-related traits rather
      than on fecundity. As revealed by stable isotope analyses, specimens at the
      invasion front had a higher trophic position in the food web and seem to benefit
      from lower food competition. Somatic performance seems to be more important than
      investment in reproduction during the early stages of the invasion process and
      upstream-directed range expansion is not caused by out-migrating weak or juvenile
      individuals that were forced to leave high density areas due to high competition.
      This mechanism might be true for downstream introductions via drift. Greater
      abundance and densities of acanthocephalan endoparasites were observed at the
      invasion front, which contradicts the expectation that invasion success is
      determined by lower parasitic pressure in newly invaded areas. Overall, the
      pronounced changes in fish and invertebrate communities with a dominance of alien
      species suggest invasional meltdown and a shift of the upper Danube River towards
      a novel ecosystem with species that have greater resistance to goby predation.
      This seems to contribute to overcoming biological resistance and improve rapidity
      of dispersal. 

PMID- 24039855
TI  - Time of death revealed by hydrocarbons of empty puparia of Chrysomya megacephala
      (Fabricius) (Diptera: Calliphoridae): a field experiment.
AB  - Determination of the postmortem interval (PMI) is crucial for investigating
      homicide. However, there are currently only limited methods available.
      Especially, once the PMI exceeds the duration of pre-adult development of the
      flies with the adult emergence, its determination is very approximate. Herein, we
      report the regular changes in hydrocarbon composition during the weathering
      process of the puparia in the field in Chrysomya megacephala (Fabricius)
      (Diptera: Calliphoridae), one of the common species of necrophagous flies.
      Correlation analysis showed that the relative abundance of nearly all of the
      branched alkanes and alkenes decreased significantly with the weathering time.
      Especially, for 9 of the peaks, over 88% of the variance in their abundance was
      explained by weathering time. Further analysis indicated that the regular changes
      caused mainly by the different weathering rates of various hydrocarbons.
      Additionally, the weathering rates were found to depend on the chemical structure
      and molecular weight of the hydrocarbons. These results indicate strongly that
      hydrocarbon analysis is a powerful tool for determining the weathering time of
      the necrophagous fly puparia, and is expected to markedly improve the
      determination of the late PMI. 

PMID- 24039856
TI  - Risk factors for children's receptive vocabulary development from four to eight
      years in the longitudinal study of Australian children.
AB  - Receptive vocabulary develops rapidly in early childhood and builds the
      foundation for language acquisition and literacy. Variation in receptive
      vocabulary ability is associated with variation in children's school achievement,
      and low receptive vocabulary ability is a risk factor for under-achievement at
      school. In this study, bivariate and multivariate growth curve modelling was used
      to estimate trajectories of receptive vocabulary development in relation to a
      wide range of candidate child, maternal and family level influences on receptive
      vocabulary development from 4-8 years. The study sample comprised 4332 children
      from the first nationally representative Longitudinal Study of Australian
      Children (LSAC). Predictors were modeled as risk variables with the lowest level
      of risk as the reference category. In the multivariate model, risks for receptive
      vocabulary delay at 4 years, in order of magnitude, were: Maternal Non- English
      Speaking Background (NESB), low school readiness, child not read to at home, four
      or more siblings, low family income, low birthweight, low maternal education,
      maternal mental health distress, low maternal parenting consistency, and high
      child temperament reactivity. None of these risks were associated with a lower
      rate of growth from 4-8 years. Instead, maternal NESB, low school readiness and
      maternal mental health distress were associated with a higher rate of growth,
      although not sufficient to close the receptive vocabulary gap for children with
      and without these risks at 8 years. Socio-economic area disadvantage, was not a
      risk for low receptive vocabulary ability at 4 years but was the only risk
      associated with a lower rate of growth in receptive vocabulary ability. At 8
      years, the gap between children with and without socio-economic area disadvantage
      was equivalent to eight months of receptive vocabulary growth. These results are
      consistent with other studies that have shown that social gradients in children's
      developmental outcomes increase over time. 

PMID- 24039857
TI  - Enhancement patterns of gastric carcinoma on contrast-enhanced ultrasonography:
      relationship with clinicopathological features.
AB  - The aim of this study was to assess the relationship between the enhancement
      patterns and clinicopathological features of gastric cancer using intravenous
      contrast-enhanced ultrasonography (CEUS). In this Ethics Committee-approved
      prospective study, five hundred fifty two patients with gastric cancer who gave
      informed consent were examined preoperatively with CEUS. The enhancement pattern
      of each tumor was analyzed visually. Gross and histopathological findings on the
      postoperative specimens were compared with the preoperative CEUS findings. The
      most common CEUS pattern in differentiated gastric cancer was homogeneous
      enhancement, whereas heterogeneous enhancement was the most common pattern in
      undifferentiated gastric cancer. The proportion of heterogeneous enhancement was
      significantly different between the two histological subtypes (Chi- square =
      146.735, P<0.001). The sensitivity and specificity of early heterogeneous
      enhancement on CEUS in diagnosing undifferentiated gastric cancer were 78.84% and
      72.59% respectively. Gastric cancers with heterogeneous enhancement were more
      often Borrmann III and IV macroscopic types than those with homogeneous
      enhancement (66.56% vs. 30.80%, P<0.001), more commonly T3 and T4 depth of
      invasion than those with homogeneous enhancement (71.52% vs. 59.60%, P<0.05),
      more often showed lymphatic invasion than those with homogeneous enhancement
      (84.44% vs. 76.40%, P<0.05), and were less likely to receive curative gastrectomy
      than those with homogeneous enhancement (74.83% vs. 86.40%, P<0.005). The intra-
      and inter-observer reproducibility were both almost perfect for assessing
      enhancement patterns, with Kappa values of 0.916 (P<0.001) for intra-observer and
      0.842 (P<0.001) for inter-observer reproducibility. CEUS provided detailed
      information about tumor vascularity and contrast enhancement patterns in gastric
      cancer. CEUS is promising as a new and useful method to predict the histological
      type of gastric cancer. 

PMID- 24039858
TI  - Serological evidence of asymptomatic infections during Escherichia coli O104:H4
      outbreak in Germany in 2011.
AB  - INTRODUCTION: The largest known outbreak caused by a rare hybrid strain of Shiga
      toxin-producing E.coli (STEC) and enteroaggregative E. coli (EAEC) (E.coli
      O104:H4) of serotype O104:H4 occurred in Germany in 2011. Fenugreek sprouts acted
      as a transmission vehicle and were widely consumed in the outbreak area at the
      time of the epidemic. In total 3,842 people developed a clinical illness caused
      by this strain; however the rates of asymptomatic infections remain unclear. We
      aimed to develop a serological assay for detection of E.coli O104 LPS specific
      antibodies and to establish the post-outbreak levels of seropositivity among
      people with documented exposure to contaminated sprouts. RESULTS AND DISCUSSION:
      Developed serological assays (ELISA with 84% sensitivity, 63% specificity and
      Western Blot with 100% sensitivity, 82.5% specificity) identified 33% (16/49)
      level of asymptomatic infection. Relatively small sample size and a significant
      time- lapse between the onset of symptoms and serum samples collection (appr. 8
      weeks) might explain the assay variability. No association was found between
      clinical or demographic characteristics and assay positivity. Larger studies are
      needed to understand the complexity of human immune response and factors
      influencing development of clinical symptoms. Development of intra-outbreak
      research plans will substantially aid the conduct of more thorough scientific
      investigation during an outbreak period.

PMID- 24039859
TI  - Hepatocellular proliferation correlates with inflammatory cell and cytokine
      changes in a murine model of nonalchoholic fatty liver disease.
AB  - Nonalchoholic fatty liver disease (NAFLD) is a problem of increasing prevalence
      and clinical significance worldwide and is associated with increased risk of
      development of end stage liver disease and cirrhosis, and can be complicated by
      hepatocellular carcinoma (HCC). NAFLD is characterized by physical and molecular
      changes in the liver microenvironment which include an influx of inflammatory
      cell populations, fibrosis, changes in gene expression, and cytokine production.
      To better understand changes to the liver in the setting of steatosis, we used a
      murine model of diet induced hepatic steatosis and corroborated our results with
      human patient samples of NAFLD. Among the cellular changes, we identified a
      significant increase in hepatocellular proliferation in the setting of steatosis
      as compared to controls. Analysis of inflammatory cell populations revealed
      increased infiltration of CD11b positive myeloid and CD3 positive lymphocytic
      cell populations in steatotic livers compared to normal livers. Resident Kupffer
      cells of the liver comprise the largest percentage of these myeloid cells and
      appear to be responsible for important cytokine alterations impacting
      proliferation of cells in the liver microenvironment. Significant alterations in
      cytokine profiles in the plasma and liver tissue lysates from normal and
      steatotic mice were detected including leptin, CXCL1, CXCL2, and CXCL16 that were
      further shown to directly increase hepatocyte proliferation in vitro. This
      increased hepatocellular proliferation and turnover in the setting of steatosis
      may play important roles in the progression and complications of NAFLD. 

PMID- 24039860
TI  - Rap1 GTPase activation and barrier enhancement in rpe inhibits choroidal
      neovascularization in vivo.
AB  - Loss of barrier integrity precedes the development of pathologies such as
      metastasis, inflammatory disorders, and blood-retinal barrier breakdown present
      in neovascular age-related macular degeneration. Rap1 GTPase is involved in
      regulating both endothelial and epithelial cell junctions; the specific role of
      Rap1A vs. Rap1B isoforms is less clear. Compromise of retinal pigment epithelium
      barrier function is a contributing factor to the development of AMD. We utilized
      shRNA of Rap1 isoforms in cultured human retinal pigment epithelial cells, along
      with knockout mouse models to test the role of Rap1 on promoting RPE barrier
      properties, with emphasis on the dynamic junctional regulation that is triggered
      when the adhesion between cells is challenged. In vitro, Rap1A shRNA reduced
      steady-state barrier integrity, whereas Rap1B shRNA affected dynamic junctional
      responses. In a laser-induced choroidal neovascularization (CNV) model of macular
      degeneration, Rap1b(-/-) mice exhibited larger CNV volumes compared to wild-type
      or Rap1a(-/-) . In vivo, intravitreal injection of a cAMP analog (8CPT-2'-O-Me
      cAMP) that is a known Rap1 activator significantly reduced laser-induced CNV
      volume, which correlated with the inhibition of CEC transmigration across 8CPT
      2'O-Me-cAMP-treated RPE monolayers in vitro. Rap1 activation by 8CPT-2'-O-Me-cAMP
      treatment increased recruitment of junctional proteins and F-actin to cell-cell
      contacts, increasing both the linearity of junctions in vitro and in cells
      surrounding laser-induced lesions in vivo. We conclude that in vitro, Rap1A may
      be important for steady state barrier integrity, while Rap1B is involved more in
      dynamic junctional responses such as resistance to junctional disassembly induced
      by EGTA and reassembly of cell junctions following disruption. Furthermore,
      activation of Rap1 in vivo inhibited development of choroidal neovascular lesions
      in a laser-injury model. Our data suggest that targeting Rap1 isoforms in vivo
      with 8CPT-2'-O-Me-cAMP may be a viable pharmacological means to strengthen the
      RPE barrier against the pathological choroidal endothelial cell invasion that
      occurs in macular degeneration. 

PMID- 24039861
TI  - Transmembrane prostatic acid phosphatase (TMPAP) interacts with snapin and
      deficient mice develop prostate adenocarcinoma.
AB  - The molecular mechanisms underlying prostate carcinogenesis are poorly
      understood. Prostatic acid phosphatase (PAP), a prostatic epithelial secretion
      marker, has been linked to prostate cancer since the 1930's. However, the
      contribution of PAP to the disease remains controversial. We have previously
      cloned and described two isoforms of this protein, a secretory (sPAP) and a
      transmembrane type-I (TMPAP). The goal in this work was to understand the
      physiological function of TMPAP in the prostate. We conducted histological, ultra
      structural and genome-wide analyses of the prostate of our PAP-deficient mouse
      model (PAP(-/-)) with C57BL/6J background. The PAP(-/-) mouse prostate showed the
      development of slow-growing non-metastatic prostate adenocarcinoma. In order to
      find out the mechanism behind, we identified PAP-interacting proteins byyeast two
      hybrid assays and a clear result was obtained for the interaction of PAP with
      snapin, a SNARE-associated protein which binds Snap25 facilitating the vesicular
      membrane fusion process. We confirmed this interaction by co-localization studies
      in TMPAP-transfected LNCaP cells (TMPAP/LNCaP cells) and in vivo FRET analyses in
      transient transfected LNCaP cells. The differential gene expression analyses
      revealed the dysregulation of the same genes known to be related to synaptic
      vesicular traffic. Both TMPAP and snapin were detected in isolated exosomes. Our
      results suggest that TMPAP is involved in endo-/exocytosis and disturbed
      vesicular traffic is a hallmark of prostate adenocarcinoma. 

PMID- 24039862
TI  - Co-enriching microflora associated with culture based methods to detect
      Salmonella from tomato phyllosphere.
AB  - The ability to detect a specific organism from a complex environment is vitally
      important to many fields of public health, including food safety. For example,
      tomatoes have been implicated numerous times as vehicles of foodborne outbreaks
      due to strains of Salmonella but few studies have ever recovered Salmonella from
      a tomato phyllosphere environment. Precision of culturing techniques that target
      agents associated with outbreaks depend on numerous factors. One important factor
      to better understand is which species co-enrich during enrichment procedures and
      how microbial dynamics may impede or enhance detection of target pathogens. We
      used a shotgun sequence approach to describe taxa associated with samples pre
      enrichment and throughout the enrichment steps of the Bacteriological Analytical
      Manual's (BAM) protocol for detection of Salmonella from environmental tomato
      samples. Recent work has shown that during efforts to enrich Salmonella
      (Proteobacteria) from tomato field samples, Firmicute genera are also co-enriched
      and at least one co-enriching Firmicute genus (Paenibacillus sp.) can inhibit and
      even kills strains of Salmonella. Here we provide a baseline description of
      microflora that co-culture during detection efforts and the utility of a
      bioinformatic approach to detect specific taxa from metagenomic sequence data. We
      observed that uncultured samples clustered together with distinct taxonomic
      profiles relative to the three cultured treatments (Universal Pre-enrichment
      broth (UPB), Tetrathionate (TT), and Rappaport-Vassiliadis (RV)). There was
      little consistency among samples exposed to the same culturing medias, suggesting
      significant microbial differences in starting matrices or stochasticity
      associated with enrichment processes. Interestingly, Paenibacillus sp.
      (Salmonella inhibitor) was significantly enriched from uncultured to cultured
      (UPB) samples. Also of interest was the sequence based identification of a number
      of sequences as Salmonella despite indication by all media, that samples were
      culture negative for Salmonella. Our results substantiate the nascent utility of
      metagenomic methods to improve both biological and bioinformatic pathogen
      detection methods. 

PMID- 24039863
TI  - Targeted biomarker discovery by high throughput glycosylation profiling of human
      plasma alpha1-antitrypsin and immunoglobulin A.
AB  - Protein N-glycosylation patterns are known to show vast genetic as well as
      physiological and pathological variation and represent a large pool of potential
      biomarkers. Large-scale studies are needed for the identification and validation
      of biomarkers, and the analytical techniques required have recently been
      developed. Such methods have up to now mainly been applied to complex mixtures of
      glycoproteins in biofluids (e.g. plasma). Here, we analyzed N-glycosylation
      profiles of alpha1-antitrypsin (AAT) and immunoglobulin A (IgA) enriched
      fractions by 96-well microtitration plate based high-throughput immuno-affinity
      capturing and N-glycan analysis using multiplexed capillary gel electrophoresis
      with laser-induced fluorescence detection (CGE-LIF). Human plasma samples were
      from the Leiden Longevity Study comprising 2415 participants of different
      chronological and biological ages. Glycosylation patterns of AAT enriched
      fractions were found to be associated with chronological (calendar) age and they
      differed between females and males. Moreover, several glycans in the AAT enriched
      fraction were associated with physiological parameters marking cardiovascular and
      metabolic diseases. Pronounced differences were found between males and females
      in the glycosylation profiles of IgA enriched fractions. Our results demonstrate
      that large-scale immuno-affinity capturing of proteins from human plasma using a
      bead-based method combined with high-throughput N-glycan analysis is a powerful
      tool for the discovery of glycosylation-based biomarker candidates. 

PMID- 24039864
TI  - Omega-3 polyunsaturated Fatty acids suppress the cystic lesion formation of
      peritoneal endometriosis in transgenic mouse models.
AB  - Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling
      pathological inflammatory reactions. Endometriosis is characterized by the
      presence of endometrial tissue on the peritoneum and an exaggerated inflammatory
      environment around ectopic tissues. Here peritoneal endometriosis was reproduced
      using a mouse model in which murine endometrial fragments were inoculated into
      the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to
      omega-3 PUFAs, or wild type mice, in which it cannot, were used for the
      endometriosis model to address the actions of omega-3 PUFAs on the development of
      endometriotic lesions. The number and weight of cystic endometriotic lesions in
      fat-1 mice two weeks after inoculation were significantly less than half to those
      of controls. Mediator lipidomics revealed that cystic endometriotic lesions and
      peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15
      HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice
      was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)
      knockout (KO) and control mice with or without EPA administration were assessed
      for the endometriosis model. EPA administration decreased the number of lesions
      in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15
      LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and
      EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of
      endometriotic lesions revealed that Interleukin-6 (IL-6) expression in fat-1 mice
      was significantly lower than that in controls. These results suggest that both
      endogenous and exogenous EPA-derived PUFAs protect against the development of
      endometriosis through their anti-inflammatory effects and, in particular, the
      12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis.

PMID- 24039865
TI  - Effects of neurolytic celiac plexus block on liver regeneration in rats with
      partial hepatectomy.
AB  - Liver regeneration is the basic physiological process after partial hepatectomy
      (PH), and is important for the functional rehabilitation of the liver after acute
      hepatic injury. This study was designed to explore the effects of neurolytic
      celiac plexus block (NCPB) on liver regeneration after PH. We established a model
      of PH in rats, assessing hepatic blood flow, liver function, and serum CRP, TNF
      alpha, IL-1beta and IL-6 concentrations of the residuary liver after PH.
      Additionally, histopathological studies, immunohistochemistry, and western
      blotting were also performed. Our results indicated that NCPB treatment after PH
      improved liver regeneration and survival rates, increased hepatic blood flow,
      reduced hepatocyte damage, decreased the secretion and release of inflammatory
      cytokines, increased the expression of B cell lymphoma/leukemia-2 (Bcl-2), and
      decreased the expression of Bcl-2 associated X protein (Bax). Additionally,
      Western blotting revealed that the expression of NF-kappaB p65 and c-Jun were
      decreased in liver after NCPB. In conclusion, the results of our present study
      indicate that NCPB treatment has a favorable effect on liver regeneration after
      PH. We suggest that NCPB can be utilized as an effective therapeutic method to
      help the functional rehabilitation of the liver after acute hepatic injury or
      liver cancer surgery. 

PMID- 24039866
TI  - Personal and environmental characteristics associated with choice of active
      transport modes versus car use for different trip purposes of trips up to 7.5
      kilometers in The Netherlands.
AB  - INTRODUCTION: This explorative study examines personal and neighbourhood
      characteristics associated with short-distance trips made by car, bicycle or
      walking in order to identify target groups for future interventions. METHODS:
      Data were derived from 'Mobility Research Netherlands (2004-2009; MON)', a
      dataset including information regarding trips made by household members (n = +/
      53,000 respondents annually). Using postal codes of household addresses, MON data
      were enriched with data on neighbourhood typologies. Multilevel logistic
      modelling was used to calculate odds ratio (OR) of active transport versus car
      use associated with four different trip purposes (shopping (reference),
      commuting, taking or bringing persons or sports). A total of 277,292 short
      distance trips made by 102,885 persons were included in analyses. RESULTS:
      Compared to women shopping, women less often take active transport to sports
      clubs (OR = 0.88) and men less often take active transport for shopping (OR =
      0.92), or for bringing or taking persons (OR = 0.76). Those aged 25-34 years (OR
      = 0.83) and 35-44 years (OR = 0.96) were more likely to use active transport for
      taking or bringing persons than persons belonging to the other age groups
      (relative to trips made for shopping by those 65 years or over). A higher use of
      active transport modes by persons with an university or college degree was found
      and particularly persons living in urban-centre neighbourhoods were likely to use
      active transport modes. CONCLUSION: IN DEVELOPING POLICIES PROMOTING A MODE SHIFT
      SPECIAL ATTENTION SHOULD BE GIVEN TO THE FOLLOWING GROUPS: a) men making short
      distance trips for taking or bringing persons, b) women making short distance
      trips to sport facilities, c) persons belonging to the age groups of 25-44 years
      of age, d) Persons with a primary school or lower general secondary education
      degree and persons with a high school or secondary school degree and e) persons
      living in rural or urban-green neighbourhoods.

PMID- 24039867
TI  - The flexible fairness: equality, earned entitlement, and self-interest.
AB  - The current study explored whether earned entitlement modulated the perception of
      fairness in three experiments. A preliminary resource earning task was added
      before players decided how to allocate the resource they jointly earned.
      Participants' decision in allocation, their responses to equal or unequal offers,
      whether advantageous or disadvantageous, and subjective ratings of fairness were
      all assessed in the current study. Behavioral results revealed that participants
      proposed more generous offers and showed enhanced tolerance to disadvantageous
      unequal offers from others when they performed worse than their presumed
      "partners," while the reverse was true in the better-performance condition. The
      subjective ratings also indicated the effect of earned entitlement, such that
      worse performance was associated with higher perceived feelings of fairness for
      disadvantageous unequal offers, while better performance was associated with
      higher feelings of fairness for advantageous unequal offers. Equal offers were
      considered "fair" only when earned entitlement was even between two parties. In
      sum, the perception of fairness is modulated by an integration of egalitarian
      motivation and entitlement. In addition to justice principles, participants were
      also motivated by self-interest, such that participants placed more weight on
      entitlement in the better-performance condition than in the worse-performance
      condition. These results imply that earned entitlement is evaluated in a self
      serving way. 

PMID- 24039868
TI  - Metabolic perturbations of kidney and spleen in murine cerebral malaria: (1)H NMR
      based metabolomic study.
AB  - A significant fraction of global population is under the threat of malaria.
      Majority of annual death is due to the more complicated form of the infection
      i.e. the cerebral form, also known as Cerebral Malaria (CM). Host parasite
      interaction is known to cause a cascade of events in various tissues like brain,
      liver, kidney, and spleen. We have employed (1)H NMR based metabolomics to
      understand the specific perturbations of various tissues in CM. In our previous
      paper we have delineated the differences between CM vis-a-vis non-cerebral
      malaria (NCM) mice in serum, liver and brain. In this paper we focus on their
      differences of metabolic profile in kidney and spleen as kidney dysfunction and
      splenomegaly are known to be associated to neurological outcome of the disease.
      Moreover we have also looked into how the biological compartments (kidney, spleen
      and serum) interact with each other. The various metabolites involved in such
      interactions and their correlational aspects across the compartments have been
      studied in CM, NCM and control mice. The idea was to find out the specific
      pathways that are altered in CM mice. Our results demonstrate that both the
      kidney as well as spleen metabolism are differentially perturbed in CM with
      respect to NCM. The results point out that glutamate levels are decreased in CM
      mice with respect to NCM mice both in case of spleen and kidney while creatine,
      myo-inositol and betaine levels are increased in kidney of CM mice with respect
      to NCM mice. From the analysis of Multiway Principal Component Analysis (MPCA) we
      see that lipid metabolism and TCA cycle is altered in kidney and spleen. 

PMID- 24039869
TI  - Pentraxin-3 serum levels are associated with disease severity and mortality in
      patients with systemic inflammatory response syndrome.
AB  - The long pentraxin-3 (PTX3) is a key component of the humoral arm of the innate
      immune system. PTX3 is produced locally in response to pro-inflammatory stimuli.
      To investigate PTX3 levels and its use as a biomarker in patients with systemic
      inflammation, we developed a solid-phase enzyme-linked immunosorbent assay based
      on novel anti-PTX3 monoclonal antibodies detecting PTX3 with high sensitivity.
      The assay was applied on 261 consecutive patients admitted to an intensive care
      unit prospectively monitored with the systemic inflammatory response syndrome
      (SIRS). 100 blood donors were included as controls. PTX3 levels were elevated in
      patients (median = 71.3 ng/ml) compared with the controls (median = 0 ng/ml)
      (Mann-Whitney, p<0.0001). ROC analysis showed that PTX3 levels were significantly
      specific (85.0%) and sensitive (89.1%) to discriminate between healthy controls
      and patients (area under the curve (AUC) 0.922 (95% CI 0.892 to 0.946,
      p<0.0001)). Higher levels of PTX3 were associated with the development of sepsis,
      severe sepsis and septic shock (p = 0.0001). The serum levels of PTX3 correlated
      significantly with SAPS2 score (Spearman's rho 0.28, p<0.0001). Patients with
      high levels of PTX3 at admission did have a higher 90 day mortality rate than
      patients with the 25% lowest levels (Cox regression analysis, hazard ratio 3.0, p
      = 0.0009). In conclusion, we have established a highly sensitive and robust assay
      for measurement of PTX3 and found that its serum concentrations correlated with
      disease severity and mortality in patients with SIRS and sepsis.

PMID- 24039870
TI  - Predictability of persistent frequent attendance in primary care: a temporal and
      geographical validation study.
AB  - BACKGROUND: Frequent attenders are patients who visit their general practitioner
      exceptionally frequently. Frequent attendance is usually transitory, but some
      frequent attenders become persistent. Clinically, prediction of persistent
      frequent attendance is useful to target treatment at underlying diseases or
      problems. Scientifically it is useful for the selection of high-risk populations
      for trials. We previously developed a model to predict which frequent attenders
      become persistent. AIM: To validate an existing prediction model for persistent
      frequent attendance that uses information solely from General Practitioners'
      electronic medical records. METHODS: We applied the existing model (N = 3,045,
      2003-2005) to a later time frame (2009-2011) in the original derivation network
      (N = 4,032, temporal validation) and to patients of another network (SMILE; 2007
      2009, N = 5,462, temporal and geographical validation). Model improvement was
      studied by adding three new predictors (presence of medically unexplained
      problems, prescriptions of psychoactive drugs and antibiotics). Finally, we
      derived a model on the three data sets combined (N = 12,539). We expressed
      discrimination using histograms of the predicted values and the concordance
      statistic (c-statistic) and calibration using the calibration slope (1 = ideal)
      and Hosmer-Lemeshow tests. RESULTS: The existing model (c-statistic 0.67)
      discriminated moderately with predicted values between 7.5 and 50 percent and c
      statistics of 0.62 and 0.63, for validation in the original network and SMILE
      network, respectively. Calibration (0.99 originally) was better in SMILE than in
      the original network (slopes 0.84 and 0.65, respectively). Adding information on
      the three new predictors did not importantly improve the model (c-statistics 0.64
      and 0.63, respectively). Performance of the model based on the combined data was
      similar (c-statistic 0.65). CONCLUSION: This external validation study showed
      that persistent frequent attenders can be prospectively identified moderately
      well using data solely from patients' electronic medical records.

PMID- 24039871
TI  - Meta-analyses of 8 polymorphisms associated with the risk of the Alzheimer's
      disease.
AB  - AIMS: The aim of this study was to evaluate the combined contribution of 8
      polymorphisms to the risk of Alzheimer's disease (AD). METHODS: Through a
      comprehensive literature search for genetic variants involved in the AD
      association study, we harvested a total of 6 genes (8 polymorphisms) for the
      current meta-analyses. These genes consisted of A2M (5bp I/D and V1000I), ABCA2
      (rs908832), CHAT (1882G >A, 2384G >A), COMT (Val158Met), HTR6 (267C >T) and LPL
      (Ser447Ter). RESULTS: A total of 33 studies among 9,453 cases and 10,833 controls
      were retrieved for the meta-analyses of 8 genetic variants. It was showed that
      A2M V1000I (odd ratio (OR) = 1.26, 95% confidence interval (CI) = 1.07-1.49, P =
      0.007), rs908832 allele of ABCA2 (OR = 1.55, 95% CI = 1.12-2.16, P = 0.009),
      2384G >A of CHAT (OR = 1.22, 95% CI = 1.00-1.49, P = 0.05) and Ser447Ter of LPL
      in the Northern-American population (OR = 0.56, 95% CI = 0.35-0.91, P = 0.02)
      were significantly associated with the risk of AD. No association was found
      between the rest of the 5 polymorphisms and the risk of AD. CONCLUSION: Our
      results showed that A2M V1000I polymorphism in German, Korean, Chinese, Spanish,
      Italian and Polish populations, rs90883 of ABCA2 gene in French, American, Swiss,
      Greek and Japanese populations, 2384G >A of CHAT gene in British and Korean
      populations and LPL Ser447Ter in the Northern-American population were associated
      with the risk of AD.

PMID- 24039872
TI  - Isolation of an orally active insecticidal toxin from the venom of an Australian
      tarantula.
AB  - Many insect pests have developed resistance to existing chemical insecticides and
      consequently there is much interest in the development of new insecticidal
      compounds with novel modes of action. Although spiders have deployed insecticidal
      toxins in their venoms for over 250 million years, there is no evolutionary
      selection pressure on these toxins to possess oral activity since they are
      injected into prey and predators via a hypodermic needle-like fang. Thus, it has
      been assumed that spider-venom peptides are not orally active and are therefore
      unlikely to be useful insecticides. Contrary to this dogma, we show that it is
      possible to isolate spider-venom peptides with high levels of oral insecticidal
      activity by directly screening for per os toxicity. Using this approach, we
      isolated a 34-residue orally active insecticidal peptide (OAIP-1) from venom of
      the Australian tarantula Selenotypus plumipes. The oral LD50 for OAIP-1 in the
      agronomically important cotton bollworm Helicoverpa armigera was 104.2+/-0.6
      pmol/g, which is the highest per os activity reported to date for an insecticidal
      venom peptide. OAIP-1 is equipotent with synthetic pyrethroids and it acts
      synergistically with neonicotinoid insecticides. The three-dimensional structure
      of OAIP-1 determined using NMR spectroscopy revealed that the three disulfide
      bonds form an inhibitor cystine knot motif; this structural motif provides the
      peptide with a high level of biological stability that probably contributes to
      its oral activity. OAIP-1 is likely to be synergized by the gut-lytic activity of
      the Bacillus thuringiensis Cry toxin (Bt) expressed in insect-resistant
      transgenic crops, and consequently it might be a good candidate for trait
      stacking with Bt. 

PMID- 24039873
TI  - A behavioral evaluation of sex differences in a mouse model of severe neuronal
      migration disorder.
AB  - Disruption of neuronal migration in humans is associated with a wide range of
      behavioral and cognitive outcomes including severe intellectual disability,
      language impairment, and social dysfunction. Furthermore, malformations of
      cortical development have been observed in a number of neurodevelopmental
      disorders (e.g. autism and dyslexia), where boys are much more commonly diagnosed
      than girls (estimates around 4 to 1). The use of rodent models provides an
      excellent means to examine how sex may modulate behavioral outcomes in the
      presence of comparable abnormal neuroanatomical presentations. Initially
      characterized by Rosen et al. 2012, the BXD29- Tlr4(lps-2J) /J mouse mutant
      exhibits a highly penetrant neuroanatomical phenotype that consists of bilateral
      midline subcortical nodular heterotopia with partial callosal agenesis. In the
      current study, we confirm our initial findings of a severe impairment in rapid
      auditory processing in affected male mice. We also report that BXD29- Tlr4(lps
      2J) /J (mutant) female mice show no sparing of rapid auditory processing, and in
      fact show deficits similar to mutant males. Interestingly, female BXD29- Tlr4(lps
      2J) /J mice do display superiority in Morris water maze performance as compared
      to wild type females, an affect not seen in mutant males. Finally, we report new
      evidence that BXD29- Tlr4(lps-2J) /J mice, in general, show evidence of hyper
      social behaviors. In closing, the use of the BXD29- Tlr4(lps-2J) /J strain of
      mice - with its strong behavioral and neuroanatomical phenotype - may be highly
      useful in characterizing sex independent versus dependent mechanisms that
      interact with neural reorganization, as well as clinically relevant abnormal
      behavior resulting from aberrant neuronal migration. 

PMID- 24039874
TI  - c-Myc is essential to prevent endothelial pro-inflammatory senescent phenotype.
AB  - The proto-oncogene c-Myc is vital for vascular development and promotes tumor
      angiogenesis, but the mechanisms by which it controls blood vessel growth remain
      unclear. In the present work we investigated the effects of c-Myc knockdown in
      endothelial cell functions essential for angiogenesis to define its role in the
      vasculature. We provide the first evidence that reduction in c-Myc expression in
      endothelial cells leads to a pro-inflammatory senescent phenotype, features
      typically observed during vascular aging and pathologies associated with
      endothelial dysfunction. c-Myc knockdown in human umbilical vein endothelial
      cells using lentivirus expressing specific anti-c-Myc shRNA reduced proliferation
      and tube formation. These functional defects were associated with morphological
      changes, increase in senescence-associated-beta-galactosidase activity,
      upregulation of cell cycle inhibitors and accumulation of c-Myc-deficient cells
      in G1-phase, indicating that c-Myc knockdown in endothelial cells induces
      senescence. Gene expression analysis of c-Myc-deficient endothelial cells showed
      that senescent phenotype was accompanied by significant upregulation of growth
      factors, adhesion molecules, extracellular-matrix components and remodeling
      proteins, and a cluster of pro-inflammatory mediators, which include Angptl4,
      Cxcl12, Mdk, Tgfb2 and Tnfsf15. At the peak of expression of these cytokines,
      transcription factors known to be involved in growth control (E2f1, Id1 and Myb)
      were downregulated, while those involved in inflammatory responses (RelB, Stat1,
      Stat2 and Stat4) were upregulated. Our results demonstrate a novel role for c-Myc
      in the prevention of vascular pro-inflammatory phenotype, supporting an important
      physiological function as a central regulator of inflammation and endothelial
      dysfunction. 

PMID- 24039876
TI  - Absence of ancient DNA in sub-fossil insect inclusions preserved in
      'Anthropocene' Colombian copal.
AB  - Insects preserved in copal, the sub-fossilized resin precursor of amber, have
      potential value in molecular ecological studies of recently-extinct species and
      of extant species that have never been collected as living specimens. The
      objective of the work reported in this paper was therefore to determine if
      ancient DNA is present in insects preserved in copal. We prepared DNA libraries
      from two stingless bees (Apidae: Meliponini: Trigonisca ameliae) preserved in
      'Anthropocene' Colombian copal, dated to 'post-Bomb' and 10,612+/-62 cal yr BP,
      respectively, and obtained sequence reads using the GS Junior 454 System. Read
      numbers were low, but were significantly higher for DNA extracts prepared from
      crushed insects compared with extracts obtained by a non-destructive method. The
      younger specimen yielded sequence reads up to 535 nucleotides in length, but
      searches of these sequences against the nucleotide database revealed very few
      significant matches. None of these hits was to stingless bees though one read of
      97 nucleotides aligned with two non-contiguous segments of the mitochondrial
      cytochrome oxidase subunit I gene of the East Asia bumblebee Bombus hypocrita.
      The most significant hit was for 452 nucleotides of a 470-nucleotide read that
      aligned with part of the genome of the root-nodulating bacterium Bradyrhizobium
      japonicum. The other significant hits were to proteobacteria and an actinomycete.
      Searches directed specifically at Apidae nucleotide sequences only gave short and
      insignificant alignments. All of the reads from the older specimen appeared to be
      artefacts. We were therefore unable to obtain any convincing evidence for the
      preservation of ancient DNA in either of the two copal inclusions that we
      studied, and conclude that DNA is not preserved in this type of material. Our
      results raise further doubts about claims of DNA extraction from fossil insects
      in amber, many millions of years older than copal. 

PMID- 24039875
TI  - PKD1 mediates negative feedback of PI3K/Akt activation in response to G protein
      coupled receptors.
AB  - We examined whether protein kinase D1 (PKD1) mediates negative feeback of
      PI3K/Akt signaling in intestinal epithelial cells stimulated with G protein
      coupled receptor (GPCR) agonists. Exposure of intestinal epithelial IEC-18 cells
      to increasing concentrations of the PKD family inhibitor kb NB 142-70, at
      concentrations that inhibited PKD1 activation, strikingly potentiated Akt
      phosphorylation at Thr(308) and Ser(473) in response to the mitogenic GPCR
      agonist angiotensin II (ANG II). Enhancement of Akt activation by kb NB 142-70
      was also evident in cells with other GPCR agonists, including vasopressin and
      lysophosphatidic acid. Cell treatment with the structurally unrelated PKD family
      inhibitor CRT0066101 increased Akt phosphorylation as potently as kb NB 142-70
      [corrected]. Knockdown of PKD1 with two different siRNAs strikingly enhanced Akt
      phosphorylation in response to ANG II stimulation in IEC-18 cells. To determine
      whether treatment with kb NB 142-70 enhances accumulation of phosphatidylinositol
      (3,4,5)-trisphosphate (PIP3) in the plasma membrane, we monitored the
      redistribution of Akt-pleckstrin homology domain-green fluorescent protein (Akt
      PH-GFP) in single IEC-18 cells. Exposure to kb NB 142-70 strikingly increased
      membrane accumulation of Akt-PH-GFP in response to ANG II. The translocation of
      the PIP3 sensor to the plasma membrane and the phosphorylation of Akt was
      completed prevented by prior exposure to the class I p110alpha specific inhibitor
      A66. ANG II markedly increased the phosphorylation of p85alpha detected by a PKD
      motif-specific antibody and enhanced the association of p85alpha with PTEN.
      Transgenic mice overexpressing PKD1 showed a reduced phosphorylation of Akt at
      Ser(473) in intestinal epithelial cells compared to wild type littermates.
      Collectively these results indicate that PKD1 activation mediates feedback
      inhibition of PI3K/Akt signaling in intestinal epithelial cells in vitro and in
      vivo.

PMID- 24039877
TI  - Health and economic burden of post-partum Staphylococcus aureus breast abscess.
AB  - OBJECTIVES: To determine the health and economic burdens of post-partum
      Staphylococcus aureus breast abscess. STUDY DESIGN: We conducted a matched cohort
      study (N = 216) in a population of pregnant women (N = 32,770) who delivered at
      our center during the study period from 10/1/03-9/30/10. Data were extracted from
      hospital databases, or via chart review if unavailable electronically. We
      compared cases of S. aureus breast abscess to controls matched by delivery date
      to compare health services utilization and mean attributable medical costs in
      2012 United States dollars using Medicare and hospital-based estimates. We also
      evaluated whether resource utilization and health care costs differed between
      cases with methicillin-resistant and -susceptible S. aureus isolates. RESULTS:
      Fifty-four cases of culture-confirmed post-partum S. aureus breast abscess were
      identified. Breastfeeding cessation (41%), milk fistula (11.1%) and hospital
      readmission (50%) occurred frequently among case patients. Breast abscess case
      patients had high rates of health services utilization compared to controls,
      including high rates of imaging and drainage procedures. The mean attributable
      cost of post-partum S. aureus breast abscess ranged from $2,340-$4,012, depending
      on the methods and data sources used. Mean attributable costs were not
      significantly higher among methicillin-resistant vs. -susceptible S. aureus
      cases. CONCLUSIONS: Post-partum S. aureus breast abscess is associated with worse
      health and economic outcomes for women and their infants, including high rates of
      breastfeeding cessation. Future study is needed to determine the optimal
      treatment and prevention of these infections.

PMID- 24039878
TI  - Assessing the validity of asthma associations for eight candidate genes and age
      at diagnosis effects.
AB  - BACKGROUND: Before the advent of genome-wide association studies (GWAS), ADAM33,
      ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most
      replicated non-HLA candidate genes with asthma and related traits. However,
      except for the IL13-IL4 region, none of these genes have been found in close
      proximity of genome-wide significant hits among GWAS for asthma or related
      traits. Here we aimed to assess the reproducibility of these asthma associations
      and to test if associations were more evident considering the effect of age at
      diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: We systematically evaluated 286 common
      single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865
      unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that
      variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects
      with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance
      after the multiple comparison adjustment. In addition, in silico replication with
      GWAS data supported the association of IL4R. CONCLUSIONS/SIGNIFICANCE: Our
      results support the important role of MS4A2, IL4R and ADAM33 genes in asthma
      and/or atopy susceptibility. However, additional studies in larger samples sets
      are needed to firmly implicate these genes in asthma susceptibility, and also to
      identify the causal variation underlying the associations found.

PMID- 24039879
TI  - Are we afraid of different categories of stimuli in identical ways? Evidence from
      skin conductance responses.
AB  - Studies have shown that emotional pictures attract more attention than neutral
      pictures, and pictures of living stimuli have similar advantage in driving
      attention (vs. nonliving). However, factors of emotion, category and picture
      context are usually mixed so that whether living and nonliving categories elicit
      different skin conductance (SC) responses, in both conscious and unconscious
      conditions, remains to be clarified. In this study, participants were presented
      with negative and neutral pictures denoting different living and nonliving
      concepts in conscious (Experiments 1 and 2) and unconscious conditions (40ms,
      Experiment 3) when their SC responses were measured. The picture context was
      manipulated in Experiments 2 and 3 as half including human-related information.
      In three experiments, the emotional levels of different categories were matched
      in different and identical cohorts of participants. The results showed that
      living pictures in a negative, high-arousing dimension elicited stronger SC
      responses than nonliving pictures. When nonhuman animals and inanimate objects
      were compared, the increased SC responses to animals was obtained only for
      negative pictures without human contexts in the conscious condition, but
      regardless of human context in the unconscious condition. These results suggested
      that contextual information and level of conscious awareness are important to
      modulate the animate advantage in emotional processing. 

PMID- 24039880
TI  - Magnesium homeostasis in cardiac myocytes of Mg-deficient rats.
AB  - To study possible modulation of Mg(2+) transport in low Mg(2+) conditions, we fed
      either a Mg-deficient diet or a Mg-containing diet (control) to Wistar rats for 1
      6 weeks. Total Mg concentrations in serum and cardiac ventricular tissues were
      measured by atomic absorption spectroscopy. Intracellular free Mg(2+)
      concentration ([Mg(2+)]i) of ventricular myocytes was measured with the
      fluorescent indicator furaptra. Mg(2+) transport rates, rates of Mg(2+) influx
      and Mg(2+) efflux, were estimated from the rates of change in [Mg(2+)]i during Mg
      loading/depletion and recovery procedures. In Mg-deficient rats, the serum total
      Mg concentration (0.29+/-0.026 mM) was significantly lower than in control rats
      (0.86+/-0.072 mM) after 4-6 weeks of Mg deficiency. However, neither total Mg
      concentration in ventricular tissues nor [Mg(2+)]i of ventricular myocytes was
      significantly different between Mg-deficient rats and control rats. The rates of
      Mg(2+) influx and efflux were not significantly different in both groups. In
      addition, quantitative RT-PCR revealed that Mg deficiency did not substantially
      change mRNA expression levels of known Mg(2+) channels/transporters (TRPM6,
      TRPM7, MagT1, SLC41A1 and ACDP2) in heart and kidney tissues. These results
      suggest that [Mg(2+)]i as well as the total Mg content of cardiac myocytes, was
      well maintained even under chronic hypomagnesemia without persistent modulation
      in function and expression of major Mg(2+) channels/transporters in the heart. 

PMID- 24039881
TI  - AFLP polymorphisms allow high resolution genetic analysis of American Tegumentary
      Leishmaniasis agents circulating in Panama and other members of the Leishmania
      genus.
AB  - American Tegumentary Leishmaniasis is caused by parasites of the genus
      Leishmania, and causes significant health problems throughout the Americas. In
      Panama, Leishmania parasites are endemic, causing thousands of new cases every
      year, mostly of the cutaneous form. In the last years, the burden of the disease
      has increased, coincident with increasing disturbances in its natural sylvatic
      environments. The study of genetic variation in parasites is important for a
      better understanding of the biology, population genetics, and ultimately the
      evolution and epidemiology of these organisms. Very few attempts have been made
      to characterize genetic polymorphisms of parasites isolated from Panamanian
      patients of cutaneous leishmaniasis. Here we present data on the genetic
      variability of local isolates of Leishmania, as well as specimens from several
      other species, by means of Amplified Fragment Length Polymorphisms (AFLP), a
      technique seldom used to study genetic makeup of parasites. We demonstrate that
      this technique allows detection of very high levels of genetic variability in
      local isolates of Leishmania panamensis in a highly reproducible manner. The
      analysis of AFLP fingerprints generated by unique selective primer combinations
      in L. panamensis suggests a predominant clonal mode of reproduction. Using
      fluorescently labeled primers, many taxon-specific fragments were identified
      which may show potential as species diagnostic fragments. The AFLP permitted a
      high resolution genetic analysis of the Leishmania genus, clearly separating
      certain groups among L. panamensis specimens and highly related species such as
      L. panamensis and L. guyanensis. The phylogenetic networks reconstructed from our
      AFLP data are congruent with established taxonomy for the genus Leishmania, even
      when using single selective primer combinations. Results of this study
      demonstrate that AFLP polymorphisms can be informative for genetic
      characterization in Leishmania parasites, at both intra and inter-specific
      levels. 

PMID- 24039882
TI  - Association between circulating fibroblast growth factor 23, alpha-Klotho, and
      the left ventricular ejection fraction and left ventricular mass in cardiology
      inpatients.
AB  - BACKGROUND: Fibroblast growth factor 23 (FGF23), with its co-receptor Klotho,
      plays a crucial role in phosphate metabolism. Several recent studies suggested
      that circulating FGF23 and alpha-Klotho concentrations might be related to
      cardiovascular abnormalities in patients with advanced renal failure. PURPOSE:
      Using data from 100 cardiology inpatients who were not undergoing chronic
      hemodialysis, the association of circulating levels of FGF23, alpha-Klotho, and
      other calcium-phosphate metabolism-related parameters with the left ventricular
      ejection fraction (LVEF) and left ventricular mass (LVM) was analyzed. METHODS
      AND RESULTS: LVEF was measured using the modified Simpson method for apical 4
      chamber LV images and the LVM index (LVMI) was calculated by dividing the LVM by
      body surface area. Univariate analysis showed that log transformed FGF23, but not
      that of alpha-Klotho, was significantly associated with LVEF and LVMI with a
      standardized beta of -0.35 (P<0.001) and 0.26 (P<0.05), respectively. After
      adjusting for age, sex, estimated glomerular filtration rate, and serum
      concentrations of intact parathyroid hormone, and 25-hydroxyvitamin D as
      covariates into the statistical model, log-transformed FGF23 was found to be a
      statistically positive predictor for decreased left ventricular function and left
      ventricular hypertrophy. CONCLUSIONS: In cardiology department inpatients,
      circulating FGF23 concentrations were found to be associated with the left
      ventricular mass and LVEF independent of renal function and other calcium
      phosphate metabolism-related parameters. Whether modulation of circulating FGF23
      levels would improve cardiac outcome in such a high risk population awaits
      further investigation.

PMID- 24039883
TI  - A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to
      hypernatremia in rats.
AB  - Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group)
      contribute to cardiovascular regulation. The present study assessed whether
      specific lesions in the A1 group altered the cardiovascular responses that were
      evoked by hypertonic saline (HS) infusion in non-anesthetized rats. Male Wistar
      rats (280-340 g) received nanoinjections of antidopamine-beta-hydroxylase-saporin
      (A1 lesion, 0.105 ng.nL(-1)) or free saporin (sham, 0.021 ng.nL(-1)) into their
      CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2) and their
      femoral artery and vein were catheterized and led to exit subcutaneously between
      the scapulae. On the following day, the animals were submitted to HS infusion (3
      M NaCl, 1.8 ml * kg(-1), b.wt., for longer than 1 min). In the sham-group (n =
      8), HS induced a sustained pressor response (DeltaMAP: 35+/-3.6 and 11+/-1.8
      mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline).
      Ten min after HS infusion, the pressor responses of the anti-DbetaH-saporin
      treated rats (n = 11)were significantly smaller(DeltaMAP: 18+/-1.4 mmHg; P<0.05
      vs. baseline and vs. sham group), and at 90 min, their blood pressures reached
      baseline values (2+/-1.6 mmHg). Compared to the sham group, the natriuresis that
      was induced by HS was reduced in the lesioned group 60 min after the challenge
      (196+/-5.5 mM vs. 262+/-7.6 mM, respectively; P<0.05). In addition, A1-lesioned
      rats excreted only 47% of their sodium 90 min after HS infusion, while sham
      animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a
      substantial destruction of the A1 cell group in the CVLM of rats that had been
      nanoinjected withanti-DbetaH-saporin. These results suggest that medullary
      noradrenergic A1 neurons are involved in the excitatory neural pathway that
      regulates hypertensive and natriuretic responses to acute changes in the
      composition of body fluid. 

PMID- 24039884
TI  - Dissection of miRNA-miRNA interaction in esophageal squamous cell carcinoma.
AB  - The relationships between miRNAs and their regulatory influences in esophageal
      carcinoma remain largely unknown. Accumulated evidence suggests that delineation
      of subpathways within an entire pathway can underlie complex diseases. To analyze
      the regulation of differentially expressed miRNAs in subpathways of esophageal
      squamous cell carcinoma (ESCC), we constructed bipartite miRNA and subpathway
      networks to determine miRNA regulatory influences on subpathways. The miRNA
      subpathway network indicated that miRNAs regulate numerous subpathways. Two
      principal biological networks were derived from the miRNA-subpathway network by
      the hypergeometric test. This miRNA-miRNA network revealed the co-regulation of
      subpathways between the upregulated and downregulated miRNAs. Subpathway
      subpathway networks characterized scale free, small world, and modular
      architecture. K-clique analysis revealed co-regulation of subpathways between
      certain downregulated and upregulated miRNAs. When ESCC patients were grouped
      according to their expression levels of paired upregulation of miR-31 and
      downregulation of miR-338-3p, survival time analysis revealed a significant
      difference based on miR-31-miR-338-3p interaction. These findings can facilitate
      the understanding of the biological meaning of miRNA-miRNA interactions with
      either the same or opposite expression trend. 

PMID- 24039885
TI  - The FEAR protein Slk19 restricts Cdc14 phosphatase to the nucleus until the end
      of anaphase, regulating its participation in mitotic exit in Saccharomyces
      cerevisiae.
AB  - In Saccharomyces cerevisiae mitosis, the protein Slk19 plays an important role in
      the initial release of Cdc14 phosphatase from the nucleolus to the nucleus in
      early anaphase, an event that is critical for proper anaphase progression. A role
      for Slk19 in later mitotic stages of Cdc14 regulation, however, has not been
      demonstrated. While investigating the role of Slk19 post-translational
      modification on Cdc14 regulation, we found that a triple point mutant of SLK19,
      slk19(3R) (three lysine-to-arginine mutations), strongly affects Cdc14
      localization during late anaphase and mitotic exit. Using fluorescence live-cell
      microscopy, we found that, similar to slk19Delta cells, slk19(3R) cells exhibit
      no defect in spindle stability and only a mild defect in spindle elongation
      dynamics. Unlike slk19Deltacells, however, slk19(3R) cells exhibit no defect in
      Cdc14 release from the nucleolus to the nucleus. Instead, slk19(3R) cells are
      defective in the timing of Cdc14 movement from the nucleus to the cytoplasm at
      the end of anaphase. This mutant has a novel phenotype: slk19(3R) causes
      premature Cdc14 movement to the cytoplasm prior to, rather than concomitant with,
      spindle disassembly. One consequence of this premature Cdc14 movement is the
      inappropriate activation of the mitotic exit network, made evident by the fact
      that slk19(3R) partially rescues a mutant of the mitotic exit network kinase
      Cdc15. In conclusion, in addition to its role in regulating Cdc14 release from
      the nucleolus to the nucleus, we found that Slk19 is also important for
      regulating Cdc14 movement from the nucleus to the cytoplasm at the end of
      anaphase. 

PMID- 24039886
TI  - Non-lethal heat shock increased Hsp70 and immune protein transcripts but not
      Vibrio tolerance in the white-leg shrimp.
AB  - Non-lethal heat shock boosts bacterial and viral disease tolerance in shrimp,
      possibly due to increases in endogenous heat shock protein 70 (Hsp70) and/or
      immune proteins. To further understand the mechanisms protecting shrimp against
      infection, Hsp70 and the mRNAs encoding the immune-related proteins
      prophenoloxidase (proPO), peroxinectin, penaeidin, crustin and hemocyanin were
      studied in post-larvae of the white-leg shrimp Litopenaeus vannamei, following a
      non-lethal heat shock. As indicated by RT-qPCR, a 30 min abrupt heat shock
      increased Hsp70 mRNA in comparison to non-heated animals. Immunoprobing of
      western blots and quantification by ELISA revealed that Hsp70 production after
      heat shock was correlated with enhanced Hsp70 mRNA. proPO and hemocyanin mRNA
      levels were augmented, whereas peroxinectin and crustin mRNA levels were
      unchanged following non-lethal heat shock. Penaeidin mRNA was decreased by all
      heat shock treatments. Thirty min abrupt heat shock failed to improve survival of
      post-larvae in a standardized challenge test with Vibrio harveyi, indicating that
      under the conditions of this study, L. vannamei tolerance to Vibrio infection was
      influenced neither by Hsp70 accumulation nor the changes in the immune-related
      proteins, observations dissimilar to other shrimp species examined. 

PMID- 24039888
TI  - The environmental price tag on a ton of mountaintop removal coal.
AB  - While several thousand square kilometers of land area have been subject to
      surface mining in the Central Appalachians, no reliable estimate exists for how
      much coal is produced per unit landscape disturbance. We provide this estimate
      using regional satellite-derived mine delineations and historical county-level
      coal production data for the period 1985-2005, and further relate the aerial
      extent of mining disturbance to stream impairment and loss of ecosystem carbon
      sequestration potential. To meet current US coal demands, an area the size of
      Washington DC would need to be mined every 81 days. A one-year supply of coal
      would result in ~2,300 km of stream impairment and a loss of ecosystem carbon
      sequestration capacity comparable to the global warming potential of >33,000 US
      homes. For the first time, the environmental impacts of surface coal mining can
      be directly scaled with coal production rates. 

PMID- 24039887
TI  - Seroprevalence of antibodies against highly pathogenic avian influenza A (H5N1)
      virus among poultry workers in Bangladesh, 2009.
AB  - We conducted a cross-sectional study in 2009 to determine the seroprevalence and
      risk factors for highly pathogenic avian influenza A (H5N1) [HPAI H5N1] virus
      antibodies among poultry workers at farms and live bird markets with
      confirmed/suspected poultry outbreaks during 2009 in Bangladesh. We tested sera
      by microneutralization assay using A/Bangladesh/207095/2008 (H5N1; clade 2.2.2)
      virus with confirmation by horse red blood cell hemagglutination inhibition and
      H5-specific Western blot assays. We enrolled 212 workers from 87 farms and 210
      workers from three live bird markets. One hundred and two farm workers (48%)
      culled poultry. One hundred and ninety-three farm workers (91%) and 178 market
      workers (85%) reported direct contact with poultry that died during a laboratory
      confirmed HPAI H5N1 poultry farm outbreak or market poultry die-offs from
      suspected HPAI H5N1. Despite exposure to sick poultry, no farm or market poultry
      workers were seropositive for HPAI H5N1 virus antibodies (95% confidence interval
      0-1%). 

PMID- 24039889
TI  - A framework for assessing global change risks to forest carbon stocks in the
      United States.
AB  - Among terrestrial environments, forests are not only the largest long-term sink
      of atmospheric carbon (C), but are also susceptible to global change themselves,
      with potential consequences including alterations of C cycles and potential C
      emission. To inform global change risk assessment of forest C across large
      spatial/temporal scales, this study constructed and evaluated a basic risk
      framework which combined the magnitude of C stocks and their associated
      probability of stock change in the context of global change across the US. For
      the purposes of this analysis, forest C was divided into five pools, two live
      (aboveground and belowground biomass) and three dead (dead wood, soil organic
      matter, and forest floor) with a risk framework parameterized using the US's
      national greenhouse gas inventory and associated forest inventory data across
      current and projected future Koppen-Geiger climate zones (A1F1 scenario). Results
      suggest that an initial forest C risk matrix may be constructed to focus
      attention on short- and long-term risks to forest C stocks (as opposed to
      implementation in decision making) using inventory-based estimates of total
      stocks and associated estimates of variability (i.e., coefficient of variation)
      among climate zones. The empirical parameterization of such a risk matrix
      highlighted numerous knowledge gaps: 1) robust measures of the likelihood of
      forest C stock change under climate change scenarios, 2) projections of forest C
      stocks given unforeseen socioeconomic conditions (i.e., land-use change), and 3)
      appropriate social responses to global change events for which there is no
      contemporary climate/disturbance analog (e.g., severe droughts in the Lake
      States). Coupling these current technical/social limits of developing a risk
      matrix to the biological processes of forest ecosystems (i.e., disturbance events
      and interaction among diverse forest C pools, potential positive feedbacks, and
      forest resiliency/recovery) suggests an operational forest C risk matrix remains
      elusive. 

PMID- 24039890
TI  - Functional characterization of the human mariner transposon Hsmar2.
AB  - DNA transposons are mobile elements with the ability to mobilize and transport
      genetic information between different chromosomal loci. Unfortunately, most
      transposons copies are currently inactivated, little is known about mariner
      elements in humans despite their role in the evolution of the human genome, even
      though the Hsmar2 transposon is associated to hotspots for homologous
      recombination involved in human genetic disorders as Charcot-Marie-Tooth, Prader
      Willi/Angelman, and Williams syndromes. This manuscript describes the functional
      characterization of the human HSMAR2 transposase generated from fossil sequences
      and shows that the native HSMAR2 is active in human cells, but also in bacteria,
      with an efficiency similar to other mariner elements. We observe that the sub
      cellular localization of HSMAR2 is dependent on the host cell type, and is
      cytotoxic when overexpressed in HeLa cells. Finally, we also demonstrate that the
      binding of HSMAR2 to its own ITRs is specific, and that the excision reaction
      leaves non-canonical footprints both in bacteria and eukaryotic cells. 

PMID- 24039891
TI  - Beta cell 5'-shifted isomiRs are candidate regulatory hubs in type 2 diabetes.
AB  - Next-generation deep sequencing of small RNAs has unveiled the complexity of the
      microRNA (miRNA) transcriptome, which is in large part due to the diversity of
      miRNA sequence variants ("isomiRs"). Changes to a miRNA's seed sequence
      (nucleotides 2-8), including shifted start positions, can redirect targeting to a
      dramatically different set of RNAs and alter biological function. We performed
      deep sequencing of small RNA from mouse insulinoma (MIN6) cells (widely used as a
      surrogate for the study of pancreatic beta cells) and developed a bioinformatic
      analysis pipeline to profile isomiR diversity. Additionally, we applied the
      pipeline to recently published small RNA-seq data from primary human beta cells
      and whole islets and compared the miRNA profiles with that of MIN6. We found
      that: (1) the miRNA expression profile in MIN6 cells is highly correlated with
      those of primary human beta cells and whole islets; (2) miRNA loci can generate
      multiple highly expressed isomiRs with different 5'-start positions (5'-isomiRs);
      (3) isomiRs with shifted start positions (5'-shifted isomiRs) are highly
      expressed, and can be as abundant as their unshifted counterparts (5'-reference
      miRNAs). Finally, we identified 10 beta cell miRNA families as candidate
      regulatory hubs in a type 2 diabetes (T2D) gene network. The most significant
      candidate hub was miR-29, which we demonstrated regulates the mRNA levels of
      several genes critical to beta cell function and implicated in T2D. Three of the
      candidate miRNA hubs were novel 5'-shifted isomiRs: miR-375+1, miR-375-1 and miR
      183-5p+1. We showed by in silico target prediction and in vitro transfection
      studies that both miR-375+1 and miR-375-1 are likely to target an overlapping,
      but distinct suite of beta cell genes compared to canonical miR-375. In summary,
      this study characterizes the isomiR profile in beta cells for the first time, and
      also highlights the potential functional relevance of 5'-shifted isomiRs to T2D. 

PMID- 24039892
TI  - Exploring agricultural livelihood transitions with an agent-based virtual
      laboratory: global forces to local decision-making.
AB  - Rural populations are undergoing rapid changes in both their livelihoods and land
      uses, with associated impacts on ecosystems, global biogeochemistry, and climate
      change. A primary challenge is, thus, to explain these shifts in terms of the
      actors and processes operating within a variety of land systems in order to
      understand how land users might respond locally to future changes in broader
      scale environmental and economic conditions. Using 'induced intensification'
      theory as a benchmark, we develop a generalized agent-based model to investigate
      mechanistic explanations of relationships between agricultural intensity and
      population density, environmental suitability, and market influence. Land-use and
      livelihood decisions modeled from basic micro-economic theories generated spatial
      and temporal patterns of agricultural intensification consistent with predictions
      of induced intensification theory. Further, agent actions in response to
      conditions beyond those described by induced intensification theory were
      explored, revealing that interactions among environmental constraints, population
      pressure, and market influence may produce transitions to multiple livelihood
      regimes of varying market integration. The result is new hypotheses that could
      modify and enrich understanding of the classic relationship between agricultural
      intensity and population density. The strength of this agent-based model and the
      experimental results is the generalized form of the decision-making processes
      underlying land-use and livelihood transitions, creating the prospect of a
      virtual laboratory for systematically generating hypotheses of how agent
      decisions and interactions relate to observed land-use and livelihood patterns
      across diverse land systems. 

PMID- 24039893
TI  - Preimplantation genetic diagnosis for a Chinese family with autosomal recessive
      Meckel-Gruber syndrome type 3 (MKS3).
AB  - Meckel-Gruber syndrome type 3 is an autosomal recessive genetic defect caused by
      mutations in TMEM67 gene. In our previous study, we have identified a homozygous
      TMEM67 mutation in a Chinese family exhibiting clinical characteristics of MKS3,
      which provided a ground for further PGD procedure. Here we report the development
      and the first clinical application of the PGD for this MKS3 family. Molecular
      analysis protocol for clinical PGD procedure was established using 50 single
      cells in pre-clinical set-up. After whole genomic amplification by multiple
      displacement amplification with the DNA from single cells, three techniques were
      applied simultaneously to increase the accuracy and reliability of genetic
      diagnosis in single blastomere, including real-time PCR with Taq Man-MGB probe,
      haplotype analysis with polymorphic STR markers and Sanger sequencing. In the
      clinical PGD cycle, nine embryos at cleavage-stage were biopsied and subjected to
      genetic diagnosis. Two embryos diagnosed as free of TMEM67 mutation were
      transferred and one achieving normal pregnancy. Non-invasive prenatal assessment
      of trisomy 13, 18 and 21 by multiplex DNA sequencing at 18 weeks' gestation
      excluded the aneuploidy of the analyzed chromosomes. A healthy boy was delivered
      by cesarean section at 39 weeks' gestation. DNA sequencing from his cord blood
      confirmed the result of genetic analysis in the PGD cycle. The protocol developed
      in this study was proved to be rapid and safe for the detection of monogenic
      mutations in clinical PGD cycle. 

PMID- 24039894
TI  - Unraveling the relationships between ecosystems and human wellbeing in Spain.
AB  - National ecosystem assessments provide evidence on the status and trends of
      biodiversity, ecosystem conditions, and the delivery of ecosystem services to
      society. I this study, we analyze the complex relationships established between
      ecosystems and human systems in Spain through the combination of Driver-Pressure
      State-Impact-Response framework and structural equation models. Firstly, to
      operationalize the framework, we selected 53 national scale indicators that
      provide accurate, long-term information on each of the components. Secondly,
      structural equation models were performed to understand the relationships among
      the components of the framework. Trend indicators have shown an overall
      progressive biodiversity loss, trade-offs between provisioning and cultural
      services associated with urban areas vs. regulating and cultural services
      associated with rural areas, a decoupling effect between material and non
      material dimensions of human wellbeing, a rapid growing trend of conservation
      responses in recent years and a constant growing linear trend of direct or
      indirect drivers of change. Results also show that all the components analyzed in
      the model are strongly related. On one hand, the model shows that biodiversity
      erosion negatively affect the supply of regulating services, while it is
      positively related with the increase of provisioning service delivery. On the
      other hand, the most important relationship found in the model is the effect of
      pressures on biodiversity loss, indicating that response options for conserving
      nature cannot counteract the effect of the drivers of change. These results
      suggest that there is an insufficient institutional response to address the
      underlying causes (indirect drivers of change) of biodiversity loos in Spain. We
      conclude that more structural changes are required in the Spanish institutional
      framework to reach 2020 biodiversity conservation international targets. 

PMID- 24039895
TI  - Cloning and characterization of a putative R2R3 MYB transcriptional repressor of
      the rosmarinic acid biosynthetic pathway from Salvia miltiorrhiza.
AB  - Salvia miltiorrhiza Bunge is one of the most renowned traditional medicinal
      plants in China. Phenolic acids that are derived from the rosmarinic acid
      pathway, such as rosmarinic acid and salvianolic acid B, are important bioactive
      components in S. miltiorrhiza. Accumulations of these compounds have been
      reported to be induced by various elicitors, while little is known about
      transcription factors that function in their biosynthetic pathways. We cloned a
      subgroup 4 R2R3 MYB transcription factor gene (SmMYB39) from S. miltiorrhiza and
      characterized its roles through overexpression and RNAi-mediated silencing. As
      the results showed, the content of 4-coumaric acid, rosmarinic acid, salvianolic
      acid B, salvianolic acid A and total phenolics was dramatically decreased in
      SmMYB39-overexpressing S. miltiorrhiza lines while being enhanced by folds in
      SmMYB39-RNAi lines. Quantitative real-time PCR and enzyme activities analyses
      showed that SmMYB39 negatively regulated transcripts and enzyme activities of 4
      hydroxylase (C4H) and tyrosine aminotransferase (TAT). These data suggest that
      SmMYB39 is involved in regulation of rosmarinic acid pathway and acts as a
      repressor through suppressing transcripts of key enzyme genes. 

PMID- 24039896
TI  - Anxiety, affect, self-esteem, and stress: mediation and moderation effects on
      depression.
AB  - BACKGROUND: Mediation analysis investigates whether a variable (i.e., mediator)
      changes in regard to an independent variable, in turn, affecting a dependent
      variable. Moderation analysis, on the other hand, investigates whether the
      statistical interaction between independent variables predict a dependent
      variable. Although this difference between these two types of analysis is
      explicit in current literature, there is still confusion with regard to the
      mediating and moderating effects of different variables on depression. The
      purpose of this study was to assess the mediating and moderating effects of
      anxiety, stress, positive affect, and negative affect on depression. METHODS: Two
      hundred and two university students (males  = 93, females  = 113) completed
      questionnaires assessing anxiety, stress, self-esteem, positive and negative
      affect, and depression. Mediation and moderation analyses were conducted using
      techniques based on standard multiple regression and hierarchical regression
      analyses. MAIN FINDINGS: The results indicated that (i) anxiety partially
      mediated the effects of both stress and self-esteem upon depression, (ii) that
      stress partially mediated the effects of anxiety and positive affect upon
      depression, (iii) that stress completely mediated the effects of self-esteem on
      depression, and (iv) that there was a significant interaction between stress and
      negative affect, and between positive affect and negative affect upon depression.
      CONCLUSION: The study highlights different research questions that can be
      investigated depending on whether researchers decide to use the same variables as
      mediators and/or moderators.

PMID- 24039897
TI  - A Bmi1-miRNAs cross-talk modulates chemotherapy response to 5-fluorouracil in
      breast cancer cells.
AB  - The polycomb group transcriptional modifier Bmi1 is often upregulated in numerous
      cancers and is intensely involved in normal and cancer stem cells, and
      importantly is as a prognostic indicator for some cancers, but its role in breast
      cancer remains unclear. Here, we found Bmi1 overexpression in 5-Fu (5
      fluorouracil)-resistant MCF-7 cells (MCF-7/5-Fu) derived from MCF-7 breast cancer
      cells, MDA-MB-231 and MDA-MB-453 breast cancer cells compared to MCF-7 cells, was
      related with 5-Fu resistance and enrichment of CD44(+)/CD24(-) stem cell
      subpopulation. Bmi1 knockdown enhanced the sensitivity of breast cancer cells to
      5-Fu and 5-Fu induced apoptosis via mitochondrial apoptotic pathway, and
      decreased the fraction of CD44(+)/CD24(-) subpopulation. In addition, our
      analysis showed inverse expression pattern between Bmi1 and miR-200c and miR-203
      in selected breast cancer cell lines, and miR-200c and miR-203 directly repressed
      Bmi1 expression in protein level confirmed by luciferase reporter assay. MiR-200c
      and miR-203 overexpression in breast cancer cells downregulated Bmi1 expression
      accompanied with reversion of resistance to 5-Fu mediated by Bmi1. Inversely,
      Bmi1 overexpression inhibited miR-200c expression in MCF-7 cells, but not miR
      203, however ectopic wild-type p53 expression reversed Bmi1 mediated miR-200c
      downregulation, suggesting the repressive effect of Bmi1 on miR-200c maybe depend
      on p53. Thus, our study suggests a cross-talk between Bmi1 and miR-200c mediated
      by p53, and Bmi1 interference would improve chemotherapy efficiency in breast
      cancer via susceptive apoptosis induction and cancer stem cell enrichment
      inhibition. 

PMID- 24039898
TI  - A unique dermal dendritic cell subset that skews the immune response toward Th2.
AB  - Dendritic cell (DC) subsets in the skin and draining lymph nodes (LNs) are likely
      to elicit distinct immune response types. In skin and skin-draining LNs, a dermal
      DC subset expressing macrophage galactose-type C-type lectin 2 (MGL2/CD301b) was
      found distinct from migratory Langerhans cells (LCs) or CD103(+) dermal DCs
      (dDCs). Lower expression levels of Th1-promoting and/or cross-presentation
      related molecules were suggested by the transcriptome analysis and verified by
      the quantitative real-time PCR analysis in MGL2(+) dDCs than in CD103(+) dDCs.
      Transfer of MGL2(+) dDCs but not CD103(+) dDCs from FITC-sensitized mice induced
      a Th2-type immune response in vivo in a model of contact hypersensitivity.
      Targeting MGL2(+) dDCs with a rat monoclonal antibody against MGL2 efficiently
      induced a humoral immune response with Th2-type properties, as determined by the
      antibody subclass. We propose that the properties of MGL2(+) dDCs, are
      complementary to those of CD103(+) dDCs and skew the immune response toward a Th2
      type response. 

PMID- 24039899
TI  - Relationship between the use of inhaled steroids for chronic respiratory diseases
      and early outcomes in community-acquired pneumonia.
AB  - BACKGROUND: The role of inhaled steroids in patients with chronic respiratory
      diseases is a matter of debate due to the potential effect on the development and
      prognosis of community-acquired pneumonia (CAP). We assessed whether treatment
      with inhaled steroids in patients with chronic bronchitis, COPD or asthma and CAP
      may affect early outcome of the acute pneumonic episode. METHODS: Over 1-year
      period, all population-based cases of CAP in patients with chronic bronchitis,
      COPD or asthma were registered. Use of inhaled steroids were registered and
      patients were followed up to 30 days after diagnosis to assess severity of CAP
      and clinical course (hospital admission, ICU admission and mortality). RESULTS:
      Of 473 patients who fulfilled the selection criteria, inhaled steroids were
      regularly used by 109 (23%). In the overall sample, inhaled steroids were
      associated with a higher risk of hospitalization (OR=1.96, p = 0.002) in the
      bivariate analysis, but this effect disappeared after adjusting by other severity
      related factors (adjusted OR=1.08, p=0.787). This effect on hospitalization also
      disappeared when considering only patients with asthma (OR=1.38, p=0.542), with
      COPD alone (OR=4.68, p=0.194), but a protective effect was observed in CB
      patients (OR=0.15, p=0.027). Inhaled steroids showed no association with ICU
      admission, days to clinical recovery and mortality in the overall sample and in
      any disease subgroup. CONCLUSIONS: Treatment with inhaled steroids is not a
      prognostic factor in COPD and asthmatic patients with CAP, but could prevent
      hospitalization for CAP in patients with clinical criteria of chronic bronchitis.

PMID- 24039900
TI  - Obesity, high-molecular-weight (HMW) adiponectin, and metabolic risk factors:
      prevalence and gender-specific associations in Estonia.
AB  - BACKGROUND: The metabolic consequences of obesity are associated with an
      imbalance of adipocytokines, e.g. adiponectin. However, some obese subjects
      remain metabolically healthy and have adiponectin levels similar to normal body
      weight subjects. Current estimates of the prevalence of obesity in Estonia have
      relied only on self-report data. OBJECTIVES: To estimate the prevalence of
      obesity in Estonia, to test for associations between HMW adiponectin and
      metabolic risk factors and to test if HMW adiponectin levels differentiate
      metabolically healthy and metabolically unhealthy subjects. METHODS: We conducted
      a population-based cross-sectional multicentre study to gather history,
      examination and blood test results for 495 subjects aged 20-74. Metabolically
      healthy subjects were free from hypertension, dyslipidaemia, impaired glucose
      regulation and insulin resistance. Metabolically unhealthy subjects had at least
      one of these four metabolic abnormalities. RESULTS: The prevalence of obesity was
      29% in men and 34% in women. HMW adiponectin was positively correlated with HDL
      cholesterol and negatively correlated with triglycerides, obesity, insulin
      resistance and blood glucose. This effect was driven by metabolically unhealthy
      subjects in men, but by both metabolically healthy and metabolically unhealthy
      subjects in women. Metabolically healthy women had higher HMW adiponectin levels
      than metabolically unhealthy women. 12% of all obese subjects were metabolically
      healthy, and their HMW adiponectin levels were similar to normal weight subjects.
      CONCLUSIONS: Obesity is more prevalent in Estonian adults than previously
      thought. HMW adiponectin levels were associated with various metabolic risk
      factors in metabolically healthy women but not in metabolically healthy men. For
      both genders, HMW adiponectin differentiates metabolically healthy obese subjects
      from metabolically unhealthy obese subjects.

PMID- 24039901
TI  - A model of loggerhead sea turtle (Caretta caretta) habitat and movement in the
      oceanic North Pacific.
AB  - Habitat preferences for juvenile loggerhead turtles in the North Pacific were
      investigated with data from two several-year long tagging programs, using 224
      satellite transmitters deployed on wild and captive-reared turtles. Animals
      ranged between 23 and 81 cm in straight carapace length. Tracks were used to
      investigate changes in temperature preferences and speed of the animals with
      size. Average sea surface temperatures along the tracks ranged from 18 to 23 
      degrees C. Bigger turtles generally experienced larger temperature ranges and
      were encountered in warmer surface waters. Seasonal differences between small and
      big turtles suggest that the larger ones dive deeper than the mixed layer and
      subsequently target warmer surface waters to rewarm. Average swimming speeds were
      under 1 km/h and increased with size for turtles bigger than 30 cm. However, when
      expressed in body lengths per second (bl s(-1)), smaller turtles showed much
      higher swimming speeds (>1 bl s (-1) ) than bigger ones (0.5 bl s(-1)).
      Temperature and speed values at size estimated from the tracks were used to
      parameterize a habitat-based Eulerian model to predict areas of highest
      probability of presence in the North Pacific. The model-generated habitat index
      generally matched the tracks closely, capturing the north-south movements of
      tracked animals, but the model failed to replicate observed east-west movements,
      suggesting temperature and foraging preferences are not the only factors driving
      large-scale loggerhead movements. Model outputs could inform potential bycatch
      reduction strategies. 

PMID- 24039902
TI  - Non-additive transcriptional profiles underlie dikaryotic superiority in
      Pleurotus ostreatus laccase activity.
AB  - BACKGROUND: The basidiomycete Pleurotus ostreatus is an efficient producer of
      laccases, a group of enzymes appreciated for their use in multiple industrial
      processes. The aim of this study was to reveal the molecular basis of the
      superiority of laccase production by dikaryotic strains compared to their
      parental monokaryons. METHODOLOGY/PRINCIPAL FINDINGS: We bred and studied a set
      of dikaryotic strains starting from a meiotic population of monokaryons. We then
      completely characterised the laccase allelic composition, the laccase gene
      expression and activity profiles in the dikaryotic strain N001, in two of its
      meiotic full-sib monokaryons and in the dikaryon formed from their mating.
      CONCLUSIONS/SIGNIFICANCE: Our results suggested that the dikaryotic superiority
      observed in laccase activity was due to non-additive transcriptional increases in
      lacc6 and lacc10 genes. Furthermore, the expression of these genes was divergent
      in glucose- vs. lignocellulose-supplemented media and was highly correlated to
      the detected extracellular laccase activity. Moreover, the expression profile of
      lacc2 in the dikaryotic strains was affected by its allelic composition,
      indicating a putative single locus heterozygous advantage.

PMID- 24039903
TI  - Hypertriglyceridemic waist might be an alternative to metabolic syndrome for
      predicting future diabetes mellitus.
AB  - BACKGROUND: In some cross-sectional studies, hypertriglyceridemic waist (HTGW)
      has been recommended as an alternative to metabolic syndrome (MetS) for screening
      individuals at high risk for diabetes mellitus (DM). However, little information
      is about the predictive power of HTGW for future DM. The aims of the study were
      to assess the DM predictive power of HTGW compared with MetS based on the follow
      up data over 15 years collected from a general Chinese population. METHODS: And
      Findings: The data were collected in 1992 and then again in 2007 from the same
      group of 687 individuals without DM in 1992. For the whole population (n =687),
      multivariate analysis showed presence of HTGW was associated with a 4.1-fold
      (95%CI: 2.4-7.0, p < 0.001) increased risk and presence of MetS was associated
      with a 3.7-fold (95%CI: 2.2-6.2, p < 0.001) increased risk for future DM. For the
      population without elevated fasting plasma glucose (n = 650), multivariate
      analysis showed presence of HTGW was associated with a 3.9-fold (95%CI: 2.2-7.0,
      p < 0.001) increased risk and presence of MetS was associated with a 3.7-fold
      (95%CI: 2.1-6.6, p < 0.001) increased risk for future DM. CONCLUSIONS: HTGW could
      predict future DM independently, and the predictive power was similar to MetS.
      HTGW might be an alternative to MetS for predicting future DM. For simpler and
      fewer components, HTGW might be more practical than MetS, and it might be
      recommended in most clinical practices. This finding might be more useful for the
      individuals who only have elevated WC and TG. Although these individuals are
      without MetS, they are still at high risk for future DM, similarly to the
      individuals with MetS.

PMID- 24039905
TI  - The stack: a new bacterial structure analyzed in the Antarctic bacterium
      Pseudomonas deceptionensis M1(T) by transmission electron microscopy and
      tomography.
AB  - In recent years, improvements in transmission electron microscopy (TEM)
      techniques and the use of tomography have provided a more accurate view of the
      complexity of the ultrastructure of prokaryotic cells. Cryoimmobilization of
      specimens by rapid cooling followed by freeze substitution (FS) and sectioning,
      freeze fracture (FF) and observation of replica, or cryoelectron microscopy of
      vitreous sections (CEMOVIS) now allow visualization of biological samples close
      to their native state, enabling us to refine our knowledge of already known
      bacterial structures and to discover new ones. Application of these techniques to
      the new Antarctic cold-adapted bacterium Pseudomonasdeceptionensis M1(T) has
      demonstrated the existence of a previously undescribed cytoplasmic structure that
      does not correspond to known bacterial inclusion bodies or membranous formations.
      This structure, which we term a "stack", was mainly visualized in slow growing
      cultures of P. deceptionensis M1(T) and can be described as a set of stacked
      membranous discs usually arranged perpendicularly to the cell membrane, but not
      continuous with it, and found in variable number in different locations within
      the cell. Regardless of their position, stacks were mostly observed very close to
      DNA fibers. Stacks are not exclusive to P. deceptionensis M1(T) and were also
      visualized in slow-growing cultures of other bacteria. This new structure
      deserves further study using cryoelectron tomography to refine its configuration
      and to establish whether its function could be related to chromosome dynamics. 

PMID- 24039904
TI  - The AP-1 transcription factor c-Jun prevents stress-imposed maladaptive
      remodeling of the heart.
AB  - Systemic hypertension increases cardiac workload and subsequently induces
      signaling networks in heart that underlie myocyte growth (hypertrophic response)
      through expansion of sarcomeres with the aim to increase contractility. However,
      conditions of increased workload can induce both adaptive and maladaptive growth
      of heart muscle. Previous studies implicate two members of the AP-1 transcription
      factor family, junD and fra-1, in regulation of heart growth during hypertrophic
      response. In this study, we investigate the function of the AP-1 transcription
      factors, c-jun and c-fos, in heart growth. Using pressure overload-induced
      cardiac hypertrophy in mice and targeted deletion of Jun or Fos in
      cardiomyocytes, we show that c-jun is required for adaptive cardiac hypertrophy,
      while c-fos is dispensable in this context. c-jun promotes expression of
      sarcomere proteins and suppresses expression of extracellular matrix proteins.
      Capacity of cardiac muscle to contract depends on organization of principal thick
      and thin filaments, myosin and actin, within the sarcomere. In line with
      decreased expression of sarcomere-associated proteins, Jun-deficient
      cardiomyocytes present disarrangement of filaments in sarcomeres and actin
      cytoskeleton disorganization. Moreover, Jun-deficient hearts subjected to
      pressure overload display pronounced fibrosis and increased myocyte apoptosis
      finally resulting in dilated cardiomyopathy. In conclusion, c-jun but not c-fos
      is required to induce a transcriptional program aimed at adapting heart growth
      upon increased workload. 

PMID- 24039906
TI  - Impact of Helicobacter pylori biofilm formation on clarithromycin susceptibility
      and generation of resistance mutations.
AB  - The human gastric pathogen Helicobacter pylori forms biofilms in vitro and in
      vivo. The purpose of this study was to evaluate the effects of H. pylori biofilm
      formation in vitro on clarithromycin (CLR) susceptibility. CLR susceptibility of
      H. pylori intermediate (2-day) and mature (3-day) biofilms on glass coverslips
      was determined at concentrations from 0.03 to 0.5 ug/ml. H. pylori biofilm
      biomass was increased after treatment with CLR at minimum inhibitory
      concentration levels by up to 4-fold (2-day biofilm) and 16-fold (3-day biofilm).
      Minimum bactericidal concentrations of CLR against cells in a biofilm were higher
      (1.0 ug/ml) than that for planktonic cells (0.25 ug/ml). It was shown that the
      expression of efflux pump genes was significantly increased in biofilm cells. In
      addition, exposure of biofilms to CLR resulted in high level resistance
      generation compared to planktonic cells with increased resistance associated with
      the presence of a point mutation at either position 2142 or 2143 in the domain V
      loop of the 23S rRNA gene. These results demonstrate that H. pylori biofilm
      formation decreases the susceptibility to CLR and that H. pylori CLR resistance
      mutations are more frequently generated in biofilms than in planktonic cells. 

PMID- 24039907
TI  - Association between polymorphisms in glutathione peroxidase and selenoprotein P
      genes, glutathione peroxidase activity, HRT use and breast cancer risk.
AB  - Breast cancer (BC) is one of the most common cancers in women. Evidence suggests
      that genetic variation in antioxidant enzymes could influence BC risk, but to
      date the relationship between selenoproteins and BC risk remains unclear. In this
      report, a study population including 975 Danish cases and 975 controls matched
      for age and hormone replacement therapy (HRT) use was genotyped for five
      functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the
      antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast
      cancer risk was assessed using conditional logistic regression. Additionally pre
      diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the
      population. A 60% reduction in risk of developing overall BC and ductal BC was
      observed in women who were homozygous Thr carriers for SEPP1 rs3877899.
      Additionally, Leu carriers for GPX1 Pro198Leu polymorphism (rs1050450) were at ~2
      fold increased risk of developing a non-ductal BC. Pre-diagnosis eGPx activity
      was found to depend on genotype for rs713041 (GPX4), rs3877899 (SEPP1), and
      rs1050450 (GPX1) and on HRT use. Moreover, depending on genotype and HRT use,
      eGPx activity was significantly lower in women who developed BC later in life
      compared with controls. Furthermore, GPx1 protein levels increased in human
      breast adenocarcinoma MCF7 cells exposed to beta-estradiol and sodium selenite.In
      conclusion, our data provide evidence that SNPs in SEPP1 and GPX1 modulate risk
      of BC and that eGPx activity is modified by SNPs in SEPP1, GPX4 and GPX1 and by
      estrogens. Our data thus suggest a role of selenoproteins in BC development. 

PMID- 24039909
TI  - Spatial heterogeneity in the strength of plant-herbivore interactions under
      predation risk: the tale of bison foraging in wolf country.
AB  - Spatial heterogeneity in the strength of trophic interactions is a fundamental
      property of food web spatial dynamics. The feeding effort of herbivores should
      reflect adaptive decisions that only become rewarding when foraging gains exceed
      1) the metabolic costs, 2) the missed opportunity costs of not foraging
      elsewhere, and 3) the foraging costs of anti-predator behaviour. Two aspects of
      these costs remain largely unexplored: the link between the strength of plant
      herbivore interactions and the spatial scale of food-quality assessment, and the
      predator-prey spatial game. We modeled the foraging effort of free-ranging plains
      bison (Bison bison bison) in winter, within a mosaic of discrete meadows. Spatial
      patterns of bison herbivory were largely driven by a search for high net energy
      gains and, to a lesser degree, by the spatial game with grey wolves (Canis
      lupus). Bison decreased local feeding effort with increasing metabolic and missed
      opportunity costs. Bison herbivory was most consistent with a broad-scale
      assessment of food patch quality, i.e., bison grazed more intensively in patches
      with a low missed opportunity cost relative to other patches available in the
      landscape. Bison and wolves had a higher probability of using the same meadows
      than expected randomly. This co-occurrence indicates wolves are ahead in the
      spatial game they play with bison. Wolves influenced bison foraging at fine
      scale, as bison tended to consume less biomass at each feeding station when in
      meadows where the risk of a wolf's arrival was relatively high. Also, bison left
      more high-quality vegetation in large than small meadows. This behavior does not
      maximize their energy intake rate, but is consistent with bison playing a shell
      game with wolves. Our assessment of bison foraging in a natural setting clarifies
      the complex nature of plant-herbivore interactions under predation risk, and
      reveals how spatial patterns in herbivory emerge from multi-scale landscape
      heterogeneity. 

PMID- 24039908
TI  - RBFOX1 and RBFOX3 mutations in rolandic epilepsy.
AB  - Partial deletions of the gene encoding the neuronal splicing regulator RBFOX1
      have been reported in a range of neurodevelopmental diseases, including
      idiopathic generalized epilepsy. The RBFOX1 protein and its homologues (RBFOX2
      and RBFOX3) regulate alternative splicing of many neuronal transcripts involved
      in the homeostatic control of neuronal excitability. In this study, we explored
      if structural microdeletions and exonic sequence variations in RBFOX1, RBFOX2,
      RBFOX3 confer susceptibility to rolandic epilepsy (RE), a common idiopathic focal
      childhood epilepsy. By high-density SNP array screening of 289 unrelated RE
      patients, we identified two hemizygous deletions, a 365 kb deletion affecting two
      untranslated 5'-terminal exons of RBFOX1 and a 43 kb deletion spanning exon 3 of
      RBFOX3. Exome sequencing of 242 RE patients revealed two novel probably
      deleterious variants in RBFOX1, a frameshift mutation (p.A233Vfs*74) and a
      hexanucleotide deletion (p.A299_A300del), and a novel nonsense mutation in RBFOX3
      (p.Y287*). Although the three variants were inherited from unaffected parents,
      they were present in all family members exhibiting the RE trait clinically or
      electroencephalographically with only one exception. In contrast, no deleterious
      mutations of RBFOX1 and RBFOX3 were found in the exomes of 6503 non-RE subjects
      deposited in the Exome Variant Server database. The observed RBFOX3 exon 3
      deletion and nonsense mutation suggest that RBFOX3 represents a novel risk factor
      for RE, indicating that exon deletions and truncating mutations of RBFOX1 and
      RBFOX3 contribute to the genetic variance of partial and generalized idiopathic
      epilepsy syndromes. 

PMID- 24039910
TI  - A novel approach identifying hybrid sterility QTL on the autosomes of Drosophila
      simulans and D. mauritiana.
AB  - When species interbreed, the hybrid offspring that are produced are often
      sterile. If only one hybrid sex is sterile, it is almost always the heterogametic
      (XY or ZW) sex. Taking this trend into account, the predominant model used to
      explain the genetic basis of F1 sterility involves a deleterious interaction
      between recessive sex-linked loci from one species and dominant autosomal loci
      from the other species. This model is difficult to evaluate, however, as only a
      handful of loci influencing interspecies hybrid sterility have been identified,
      and their autosomal genetic interactors have remained elusive. One hindrance to
      their identification has been the overwhelming effect of the sex chromosome in
      mapping studies, which could 'mask' the ability to accurately map autosomal
      factors. Here, we use a novel approach employing attached-X chromosomes to create
      reciprocal backcross interspecies hybrid males that have a non-recombinant sex
      chromosome and recombinant autosomes. The heritable variation in phenotype is
      thus solely caused by differences in the autosomes, thereby allowing us to
      accurately identify the number and location of autosomal sterility loci. In one
      direction of backcross, all males were sterile, indicating that sterility could
      be entirely induced by the sex chromosome complement in these males. In the other
      direction, we identified nine quantitative trait loci that account for a
      surprisingly large amount (56%) of the autosome-induced phenotypic variance in
      sterility, with a large contribution of autosome-autosome epistatic interactions.
      These loci are capable of acting dominantly, and thus could contribute to F1
      hybrid sterility. 

PMID- 24039911
TI  - In pursuit of delay-related brain activity for anticipatory eye movements.
AB  - How the brain stores motion information and subsequently uses it to follow a
      moving target is largely unknown. This is mainly due to previous fMRI studies
      using paradigms in which the eye movements cannot be segregated from the storage
      of this motion information. To avoid this problem we used a novel paradigm
      designed in our lab in which we interlaced a delay (2, 4 or 6 seconds) between
      the 1(st) and 2(nd) presentation of a moving stimulus. Using this design we could
      examine brain activity during a delay period using fMRI and have subsequently
      found a number of brain areas that reveal sustained activity during predictive
      pursuit. These areas include, the V5 complex and superior parietal lobe. This
      study provides new evidence for the network involved in the storage of visual
      information to generate early motor responses in pursuit. 

PMID- 24039912
TI  - Effect of IRS4 levels on PI 3-kinase signalling.
AB  - Insulin receptor substrate 1 (IRS1) and IRS2 are well-characterized adapter
      proteins that relay signals from receptor tyrosine kinases to downstream
      components of signalling pathways. In contrast, the function of IRS4 is not well
      understood. IRS4 overexpression has been associated with acute lymphoblastic
      leukaemia and subungual exostosis, while point mutations of IRS4 have been found
      in melanomas. Here, we show that while IRS4 expression is low in most cancer cell
      lines, IRS4 mRNA and protein levels are markedly elevated in certain cells
      including the NCI-H720, DMS114, HEK293T and HEK293AAV lines. Surprisingly, IRS4
      expression was also strongly induced when HEK293 cells were infected with
      retroviral particles and selected under puromycin, making IRS4 expression a
      potential off-target effect of retroviral expression vectors. Cells with high
      expression of IRS4 displayed high phosphatidylinositol (3,4,5)-trisphosphate
      (PIP3) levels, as well as elevated Akt and p70 S6 kinase activities, even in the
      absence of growth factors. PI 3-kinase (PI3K) signalling in these cells depends
      on IRS4, even though these cells also express IRS1/2. Knockdown of IRS4 also
      inhibited cell proliferation in cells with high levels of IRS4. Together, these
      findings suggest IRS4 as a potential therapeutic target for cancers with high
      expression of this protein. 

PMID- 24039913
TI  - The relationship between functional inhibition and binding for K(Ca)2 channel
      blockers.
AB  - Small conductance calcium-activated potassium channels (KCa2.1,2.2,2.3) are
      blocked with high affinity by both peptide toxins (e.g. apamin) and small
      molecule blockers (e.g. UCL 1848). In electrophysiological experiments, apamin
      shows subtype selectivity with IC50s of ~100 pM and ~1 nM for block KCa2.2 and
      KCa2.3 respectively. In binding studies, however, apamin appears not to
      discriminate between KCa2.2 and 2.3 and is reported to have a significantly
      higher (~20-200-fold) affinity (~5 pM). This discrepancy between binding and
      block has been suggested to reflect an unusual mode of action of apamin. However,
      these binding and electrophysiological block experiments have not been conducted
      in the same ionic conditions, so it is also possible that the discrepancy arises
      simply because of differences in experimental conditions. We have now examined
      this latter possibility. Thus, we measured (125)I-apamin binding to intact HEK
      293 cells expressing KCa2 channels under the same ionic conditions (i.e. normal
      physiological conditions) that we also used for current block measurements. We
      find that binding and block experiments agree well if the same ionic conditions
      are used. Further, the binding of apamin and other blockers showed subtype
      selectivity when measured in normal physiological solutions (e.g.(125)I-apamin
      bound to KCa2.2 with K L 91+/-40 pM and to KCa2.3 with K L 711+/-126 pM, while
      inhibiting KCa2.2 current at IC50 103+/-2 pM). We also examined KCa2 channel
      block in Ca(2+) and Mg(2+) free solutions that mimic conditions reported in the
      literature for binding experiments. Under these (non-physiological) conditions
      the IC50 for apamin block of KCa2.2 was reduced to 20+/-3 pM. Our results
      therefore suggest that the apparent discrepancy between blocking and binding
      reported in the literature can be largely accounted for by the use of non
      physiological ionic conditions in binding experiments. 

PMID- 24039914
TI  - Prognostic significance of EDN/RB, HJURP, p60/CAF-1 and PDLI4, four new markers
      in high-grade gliomas.
AB  - BACKGROUND: Recent studies have highlighted the heterogeneity of gliomas and
      demonstrated that molecular and genetic analysis could help in their
      classification and in the design of treatment protocols. In a previous study we
      have identified a 4-gene signature highly correlated with survival of glioma
      patients. The aim of this study is to confirm and extend these findings by
      investigating the expression of these genes at the protein level and their
      association with outcome of patients with high grade gliomas.
      METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical staining for EDN/RB, HJURP,
      p60/CAF-1 and PDLI4 was studied on archive materials from 96 patients (64
      glioblastomas and 32 grade III gliomas). The levels of all four proteins differed
      significantly between grade III and grade IV tumours. The levels of the EDN/RB,
      HJURP and p60/CAF-1 proteins were strongly associated with overall survival
      (p<0.001, p<0.001 and p=0.002, respectively), whereas the one of PDLI4 was not
      (P=0.11). A risk criterion defined as high levels of at least two of the EDN/RB,
      HJURP and p60/CAF-1 proteins accurately predicted the prognosis of patients.
      Multivariate analysis confirmed that this criterion was an independent negative
      prognostic marker (hazard ratio = 2.225; 95% CI, 1.248 to 3.966, p=0.007).
      CONCLUSIONS: The expression of the EDN/RB, HJURP, p60/CAF-1 and PDLI4 proteins is
      disrupted in high grade gliomas and increases in the levels of these proteins are
      closely linked to tumour aggressiveness and poor outcome.

PMID- 24039915
TI  - Cholesterol oxidase is indispensable in the pathogenesis of Mycobacterium
      tuberculosis.
AB  - Despite considerable research effort, the molecular mechanisms of Mycobacterium
      tuberculosis (Mtb) virulence remain unclear. Cholesterol oxidase (ChoD), an
      extracellular enzyme capable of converting cholesterol to its 3-keto-4-ene
      derivative, cholestenone, has been proposed to play a role in the virulence of
      Mtb. Here, we verified the hypothesis that ChoD is capable of modifying the
      bactericidal and pro-inflammatory activity of human macrophages. We also sought
      to determine the contribution of complement receptor 3 (CR3)- and Toll-like
      receptor 2 (TLR2)-mediated signaling pathways in the development of macrophage
      responses to Mtb. We found that intracellular replication of an Mtb mutant
      lacking a functional choD gene (DeltachoD) was less efficient in macrophages than
      that of the wild-type strain. Blocking CR3 and TLR2 with monoclonal antibodies
      enhanced survival of DeltachoD inside macrophages. We also showed that, in
      contrast to wild-type Mtb, the DeltachoD strain induced nitric oxide production
      in macrophages, an action that depended on the TLR2, but not the CR3, signaling
      pathway. Both wild-type and mutant strains inhibited the production of reactive
      oxygen species (ROS), but the DeltachoD strain did so to a significantly lesser
      extent. Blocking TLR2-mediated signaling abolished the inhibitory effect of wild
      type Mtb on ROS production by macrophages. Wild-type Mtb, but not the DeltachoD
      strain, decreased phorbol myristate acetate-induced phosphorylation of
      extracellular signal-regulated kinases 1 and 2 (ERK1/2), which are involved in
      both TLR2- and CR3-mediated signaling pathways. Our finding also revealed that
      the production of interleukin 10 by macrophages was significantly lower in
      DeltachoD-infected macrophages than in wild-type Mtb-infected macrophages.
      However, tumor necrosis factor-alpha production by macrophages was the same after
      infection with mutant or wild-type strains. In summary, we demonstrate here that
      ChoD is required for Mtb interference with the TLR2-mediated signaling pathway
      and subsequent intracellular growth and survival of the pathogen in human
      macrophages. 

PMID- 24039916
TI  - Evaluation of the impact of alveolar nitrogen excretion on indices derived from
      multiple breath nitrogen washout.
AB  - BACKGROUND: A large body of evidence has now accumulated describing the
      advantages of multiple breath washout tests over conventional spirometry in
      cystic fibrosis (CF). Although the majority of studies have used exogenous
      sulphur hexafluoride (SF6) as the tracer gas this has also led to an increased
      interest in nitrogen washout tests, despite the differences between these
      methods. The impact of body nitrogen excreted across the alveoli has previously
      been ignored. METHODS: A two-compartment lung model was developed that included
      ventilation heterogeneity and dead space (DS) effects, but also incorporated
      experimental data on nitrogen excretion. The model was used to assess the impact
      of nitrogen excretion on washout progress and accuracy of functional residual
      capacity (FRC) and lung clearance index (LCI) measurements. RESULTS: Excreted
      nitrogen had a small effect on accuracy of FRC (1.8%) in the healthy adult model.
      The error in LCI calculated with true FRC was greater (6.3%), and excreted
      nitrogen contributed 21% of the total nitrogen concentration at the end of the
      washout. Increasing DS and ventilation heterogeneity both caused further increase
      in measurement error. LCI was increased by 6-13% in a CF child model, and
      excreted nitrogen increased the end of washout nitrogen concentration by 24-49%.
      CONCLUSIONS: Excreted nitrogen appears to have complex but clinically significant
      effects on washout progress, particularly in the presence of abnormal gas mixing.
      This may explain much of the previously described differences in washout outcomes
      between SF6 and nitrogen.

PMID- 24039917
TI  - Learning from simple ebooks, online cases or classroom teaching when acquiring
      complex knowledge. A randomized controlled trial in respiratory physiology and
      pulmonology.
AB  - BACKGROUND AND AIMS: E-learning is developing fast because of the rapid increased
      use of smartphones, tablets and portable computers. We might not think of it as e
      learning, but today many new e-books are in fact very complex electronic teaching
      platforms. It is generally accepted that e-learning is as effective as classroom
      teaching methods, but little is known about its value in relaying contents of
      different levels of complexity to students. We set out to investigate e-learning
      effects on simple recall and complex problem-solving compared to classroom
      teaching. METHODS: 63 nurses specializing in anesthesiology were evenly
      randomized into three groups. They were given internet-based knowledge tests
      before and after attending a teaching module about respiratory physiology and
      pulmonology. The three groups was either an e-learning group with eBook teaching
      material, an e-learning group with case-based teaching or a group with face-to
      face case-based classroom teaching. After the module the students were required
      to answer a post-test. Time spent and the number of logged into the system was
      also measured. RESULTS: For simple recall, all methods were equally effective.
      For problem-solving, the eCase group achieved a comparable knowledge level to
      classroom teaching, while textbook learning was inferior to both (p<0.01). The
      textbook group also spent the least amount of time on acquiring knowledge (33
      minutes, p<0.001), while the eCase group spent significantly more time on the
      subject (53 minutes, p<0.001) and logged into the system significantly more (2.8
      vs 1.6, p<0.001). CONCLUSIONS: E-learning based cases are an effective tool for
      teaching complex knowledge and problem-solving ability, but future studies using
      higher-level e-learning are encouraged.Simple recall skills, however, do not
      require any particular learning method.

PMID- 24039918
TI  - Epithelial-mesenchymal transition associates with maintenance of stemness in
      spheroid-derived stem-like colon cancer cells.
AB  - Despite earlier studies demonstrating characteristics of colon cancer stem cells
      (CCSCs) and the role of epithelial-mesenchymal transition (EMT) in tumor
      development, it remains controversial as to the relationship between CCSCs and
      EMT. In this study, in order to present an insight into this relationship in
      colon cancer, we developed HCT116 and HT29 sphere models, which are known to be
      the cells enriching cancer stem cells. Compared to their parental counterparts,
      spheroid cells displayed lower homotypic/heterotypic adhesion but higher in vitro
      migratory/invasive capacity, as well as higher tumorigenic and metastatic
      potential in vivo. The spheroid cells also demonstrated down-regulated E-cadherin
      and up-regulated alpha-SMA and Vimentin expression, which is the typical
      phenotype of EMT. In order to explore whether this phenomenon is associated to
      activation of Wnt/beta-catenin pathway, we detected several key signaling
      molecules. Compared with their parental cells, HCT116 and HT29 spheroid cells
      demonstrated down-regulated expression of GSK3beta, but up-regulated expression
      of Slug and Snail. And also, the up-regulation of nucleus beta-catenin in
      spheroid cells indicated that the free beta-catenin transferred from cytoplasm to
      cell nucleus. Our findings indicate that spheroid cells have the characteristics
      of colon cancer stem cells, and EMT may account for their stemness and
      malignancy. And persistent activation of Wnt/beta-catenin pathway may play an
      important role in the EMT of CCSCs. 

PMID- 24039919
TI  - Genotypic and phenotypic characterization of antimicrobial-resistant Escherichia
      coli from farm-raised diarrheic sika deer in Northeastern China.
AB  - In China, overuse and/or abuse of antimicrobials are common in stockbreeding,
      which possess high risks of antimicrobial-resistant contaminations. The
      serogroups, major virulence genes, and antimicrobial resistant patterns of the
      antimicrobial-resistant Escherichia coli (E. coli) were investigated in the feces
      of diarrheic farm-raised sika deer from 50 farms in three Northeastern provinces
      of China. A total of 220 E. coli isolates were obtained and characterized. Twenty
      eight O serogroups were identified from the obtained E. coli isolates with O2,
      O26, O128, O142 and O154 being dominant. Nearly all the isolates were resistant
      to at least four of the tested antimicrobials. More than 90% of the E. coli
      isolates carried at least one of the tested virulence genes. About 85% of the E.
      coli isolates carried one or more antimicrobial-resistant genes responsible for
      resistant phenotypes of sulfonamides, streptomycin/spectionomycin or
      tetracycline. The antimicrobial resistant level and pathogenic group occurrences
      of the obtained E. coli isolates were higher than that of livestock and wild
      animals reported in some developed countries. Thus, the fecal-carrying
      antimicrobial-resistant E. coli from the farm-raised sika deer is potentially a
      significant contamination source for freshwater systems and food chain, and may
      pose great health risks for human and animals in Northeastern China. 

PMID- 24039920
TI  - Application of concave microwells to pancreatic tumor spheroids enabling
      anticancer drug evaluation in a clinically relevant drug resistance model.
AB  - Intrinsic drug resistance of pancreatic ductal adenocarcinoma (PDAC) warrants
      studies using models that are more clinically relevant for identifying novel
      resistance mechanisms as well as for drug development. Tumor spheroids (TS) mimic
      in vivo tumor conditions associated with multicellular resistance and represent a
      promising model for efficient drug screening, however, pancreatic cancer cells
      often fail to form spheroids using conventional methods such as liquid overlay.
      This study describes the induction of TS of human pancreatic cancer cells (Panc
      1, Aspc-1, Capan-2) in concave polydimethylsiloxane (PDMS) microwell plates and
      evaluation of their usefulness as an anticancer efficacy test model. All three
      cell lines showed TS formation with varying degree of necrosis inside TS. Among
      these, Panc-1 spheroid with spherical morphology, a rather rough surface, and
      unique adhesion structures were successfully produced with no notable necrosis in
      concave microwell plates. Panc-1 TS contained growth factors or enzymes such as
      TGF-beta1, CTGF, and MT1-MMP, and extracellular matrix proteins such as collagen
      type I, fibronectin, and laminin. Panc-1 cells grown as TS showed changes in stem
      cell populations and in expression levels of miRNAs that may play roles in
      chemoresistance. Visualization of drug penetration and detection of viability
      indicators, such as Ki-67 and MitoSOX, were optimized for TS for quantitative
      analysis. Water-soluble tetrazolium (MTS) and acid phosphatase (APH) assays were
      also successfully optimized. Overall, we demonstrated that concave PDMS microwell
      plates are a novel platform for preparation of TS of weakly aggregating cells and
      that Panc-1 spheroids may represent a novel three-dimensional model for anti
      pancreatic cancer drug screening. 

PMID- 24039921
TI  - A two-component system regulates hemin acquisition in Porphyromonas gingivalis.
AB  - Porphyromonas gingivalis is a Gram-negative oral anaerobe associated with
      infection of the periodontia. The organism has a small number of two-component
      signal transduction systems, and after comparing genome sequences of strains W83
      and ATCC 33277 we discovered that the latter was mutant in histidine kinase
      (PGN_0752), while the cognate response regulator (PGN_0753) remained intact.
      Microarray-based transcriptional profiling and ChIP-seq assays were carried out
      with an ATCC 33277 transconjugant containing the functional histidine kinase from
      strain W83 (PG0719). The data showed that the regulon of this signal transduction
      system contained genes that were involved in hemin acquisition, including
      gingipains, at least three transport systems, as well as being self-regulated.
      Direct regulation by the response regulator was confirmed by electrophoretic
      mobility shift assays. In addition, the system appears to be activated by hemin
      and the regulator acts as both an activator and repressor. 

PMID- 24039922
TI  - Resection probability maps for quality assessment of glioma surgery without brain
      location bias.
AB  - BACKGROUND: Intraoperative brain stimulation mapping reduces permanent
      postoperative deficits and extends tumor removal in resective surgery for glioma
      patients. Successful functional mapping is assumed to depend on the surgical
      team's expertise. In this study, glioma resection results are quantified and
      compared using a novel approach, so-called resection probability maps (RPM),
      exemplified by a surgical team comparison, here with long and short experience in
      mapping. METHODS: Adult patients with glioma were included by two centers with
      two and fifteen years of mapping experience. Resective surgery was targeted at
      non-enhanced MRI extension and was limited by functional boundaries. Neurological
      outcome was compared. To compare resection results, we applied RPMs to quantify
      and compare the resection probability throughout the brain at 1 mm resolution.
      Considerations for spatial dependence and multiple comparisons were taken into
      account. RESULTS: The senior surgical team contributed 56, and the junior team 52
      patients. The patient cohorts were comparable in age, preoperative tumor volume,
      lateralization, and lobe localization. Neurological outcome was similar between
      teams. The resection probability on the RPMs was very similar, with none (0%) of
      703,967 voxels in left-sided tumors being differentially resected, and 124
      (0.02%) of 644,153 voxels in right-sided tumors. CONCLUSION: RPMs provide a
      quantitative volumetric method to compare resection results, which we present as
      standard for quality assessment of resective glioma surgery because brain
      location bias is avoided. Stimulation mapping is a robust surgical technique,
      because the neurological outcome and functional-based resection results using
      stimulation mapping are independent of surgical experience, supporting wider
      implementation.

PMID- 24039923
TI  - Tropaeolum tops tobacco - simple and efficient transgene expression in the order
      Brassicales.
AB  - Transient expression systems are valuable tools in molecular biology.
      Agrobacterial infiltration of leaves is well-established in tobacco, but has led
      to limited success in the model plant Arabidopsis thaliana. An efficient
      expression system combining the advantages of Arabidopsis (well-characterised)
      and the simplicity of leaf infiltration is desirable. Here, I describe
      Agrobacterium tumefaciens-mediated transformation of Tropaeolummajus (nasturtium,
      order Brassicales) as a remarkably simple, cheap and highly efficient transient
      expression system. It provides the Arabidopsis community with a tool to study
      subcellular localisation, protein-protein interactions and reporter gene
      activities (e.g. luciferase, beta-glucuronidase) in a genetic background that is
      closely related to their primary model organism. Unlike Arabidopsis, Tropaeolum
      is capable of engaging in endomycorrhizal associations and is therefore relevant
      also to symbiosis research. RNAi-based approaches are more likely to succeed than
      in the distantly-related Nicotiana transformation system. Tropaeolummajus was
      voted the "medicinal plant of the year 2013". Conquering this plant for genetic
      manipulations harbours potential for biotechnological and pharmacological
      applications. 

PMID- 24039924
TI  - Predicting relapsing-remitting dynamics in multiple sclerosis using discrete
      distribution models: a population approach.
AB  - BACKGROUND: Relapsing-remitting dynamics are a hallmark of autoimmune diseases
      such as Multiple Sclerosis (MS). A clinical relapse in MS reflects an acute focal
      inflammatory event in the central nervous system that affects signal conduction
      by damaging myelinated axons. Those events are evident in T1-weighted post
      contrast magnetic resonance imaging (MRI) as contrast enhancing lesions (CEL).
      CEL dynamics are considered unpredictable and are characterized by high intra-
      and inter-patient variability. Here, a population approach (nonlinear mixed
      effects models) was applied to analyse of CEL progression, aiming to propose a
      model that adequately captures CEL dynamics. METHODS AND FINDINGS: We explored
      several discrete distribution models to CEL counts observed in nine MS patients
      undergoing a monthly MRI for 48 months. All patients were enrolled in the study
      free of immunosuppressive drugs, except for intravenous methylprednisolone or
      oral prednisone taper for a clinical relapse. Analyses were performed with the
      nonlinear mixed-effect modelling software NONMEM 7.2. Although several models
      were able to adequately characterize the observed CEL dynamics, the negative
      binomial distribution model had the best predictive ability. Significant
      improvements in fitting were observed when the CEL counts from previous months
      were incorporated to predict the current month's CEL count. The predictive
      capacity of the model was validated using a second cohort of fourteen patients
      who underwent monthly MRIs during 6-months. This analysis also identified and
      quantified the effect of steroids for the relapse treatment. CONCLUSIONS: The
      model was able to characterize the observed relapsing-remitting CEL dynamic and
      to quantify the inter-patient variability. Moreover, the nature of the effect of
      steroid treatment suggested that this therapy helps resolve older CELs yet does
      not affect newly appearing active lesions in that month. This model could be used
      for design of future longitudinal studies and clinical trials, as well as for the
      evaluation of new therapies.

PMID- 24039925
TI  - Predictive computational modeling of the mucosal immune responses during
      Helicobacter pylori infection.
AB  - T helper (Th) cells play a major role in the immune response and pathology at the
      gastric mucosa during Helicobacter pylori infection. There is a limited
      mechanistic understanding regarding the contributions of CD4+ T cell subsets to
      gastritis development during H. pylori colonization. We used two computational
      approaches: ordinary differential equation (ODE)-based and agent-based modeling
      (ABM) to study the mechanisms underlying cellular immune responses to H. pylori
      and how CD4+ T cell subsets influenced initiation, progression and outcome of
      disease. To calibrate the model, in vivo experimentation was performed by
      infecting C57BL/6 mice intragastrically with H. pylori and assaying immune cell
      subsets in the stomach and gastric lymph nodes (GLN) on days 0, 7, 14, 30 and 60
      post-infection. Our computational model reproduced the dynamics of effector and
      regulatory pathways in the gastric lamina propria (LP) in silico. Simulation
      results show the induction of a Th17 response and a dominant Th1 response,
      together with a regulatory response characterized by high levels of mucosal Treg)
      cells. We also investigated the potential role of peroxisome proliferator
      activated receptor gamma (PPARgamma) activation on the modulation of host
      responses to H. pylori by using loss-of-function approaches. Specifically, in
      silico results showed a predominance of Th1 and Th17 cells in the stomach of the
      cell-specific PPARgamma knockout system when compared to the wild-type
      simulation. Spatio-temporal, object-oriented ABM approaches suggested similar
      dynamics in induction of host responses showing analogous T cell distributions to
      ODE modeling and facilitated tracking lesion formation. In addition, sensitivity
      analysis predicted a crucial contribution of Th1 and Th17 effector responses as
      mediators of histopathological changes in the gastric mucosa during chronic
      stages of infection, which were experimentally validated in mice. These
      integrated immunoinformatics approaches characterized the induction of mucosal
      effector and regulatory pathways controlled by PPARgamma during H. pylori
      infection affecting disease outcomes. 

PMID- 24039927
TI  - Conservation, spillover and gene flow within a network of Northern European
      marine protected areas.
AB  - To ensure that marine protected areas (MPAs) benefit conservation and fisheries,
      the effectiveness of MPA designs has to be evaluated in field studies. Using an
      interdisciplinary approach, we empirically assessed the design of a network of
      northern MPAs where fishing for European lobster (Homarusgammarus) is prohibited.
      First, we demonstrate a high level of residency and survival (50%) for almost a
      year (363 days) within MPAs, despite small MPA sizes (0.5-1 km(2)). Second, we
      demonstrate limited export (4.7%) of lobsters tagged within MPAs (N = 1810) to
      neighbouring fished areas, over a median distance of 1.6 km out to maximum 21 km
      away from MPA centres. In comparison, median movement distance of lobsters
      recaptured within MPAs was 164 m, and recapture rate was high (40%). Third, we
      demonstrate a high level of gene flow within the study region, with an estimated
      F ST of less than 0.0001 over a ~ 400 km coastline. Thus, the restricted movement
      of older life stages, combined with a high level of gene flow suggests that
      connectivity is primarily driven by larval drift. Larval export from the MPAs can
      most likely affect areas far beyond their borders. Our findings are of high
      importance for the design of MPA networks for sedentary species with pelagic
      early life stages. 

PMID- 24039926
TI  - Notch receptor expression in neurogenic regions of the adult zebrafish brain.
AB  - The adult zebrash brain has a remarkable constitutive neurogenic capacity. The
      regulation and maintenance of its adult neurogenic niches are poorly understood.
      In mammals, Notch signaling is involved in stem cell maintenance both in
      embryonic and adult CNS. To better understand how Notch signaling is involved in
      stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch
      receptor expression in five neurogenic zones of the adult zebrafish brain.
      Combining proliferation and glial markers we identified several subsets of Notch
      receptor expressing cells. We found that 90 [Formula: see text] of proliferating
      radial glia express notch1a, notch1b and notch3. In contrast, the proliferating
      non-glial populations of the dorsal telencephalon and hypothalamus rarely express
      notch3 and about half express notch1a/1b. In the non-proliferating radial glia
      notch3 is the predominant receptor throughout the brain. In the ventral
      telencephalon and in the mitotic area of the optic tectum, where cells have
      neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating
      cells. However, in the cerebellar niche, although progenitors also have
      neuroepithelial properties, only notch1a/1b are expressed in a high number of
      PCNA [Formula: see text] cells. In this region notch3 expression is mostly in
      Bergmann glia and at low levels in few PCNA [Formula: see text] cells.
      Additionally, we found that in the proliferation zone of the ventral
      telencephalon, Notch receptors display an apical high to basal low gradient of
      expression. Notch receptors are also expressed in subpopulations of
      oligodendrocytes, neurons and endothelial cells. We suggest that the partial
      regional heterogeneity observed for Notch expression in progenitor cells might be
      related to the cellular diversity present in each of these neurogenic niches. 

PMID- 24039928
TI  - Elastic coupling of nascent apCAM adhesions to flowing actin networks.
AB  - Adhesions are multi-molecular complexes that transmit forces generated by a
      cell's acto-myosin networks to external substrates. While the physical properties
      of some of the individual components of adhesions have been carefully
      characterized, the mechanics of the coupling between the cytoskeleton and the
      adhesion site as a whole are just beginning to be revealed. We characterized the
      mechanics of nascent adhesions mediated by the immunoglobulin-family cell
      adhesion molecule apCAM, which is known to interact with actin filaments. Using
      simultaneous visualization of actin flow and quantification of forces transmitted
      to apCAM-coated beads restrained with an optical trap, we found that adhesions
      are dynamic structures capable of transmitting a wide range of forces. For forces
      in the picoNewton scale, the nascent adhesions' mechanical properties are
      dominated by an elastic structure which can be reversibly deformed by up to 1 um.
      Large reversible deformations rule out an interface between substrate and
      cytoskeleton that is dominated by a number of stiff molecular springs in
      parallel, and favor a compliant cross-linked network. Such a compliant structure
      may increase the lifetime of a nascent adhesion, facilitating signaling and
      reinforcement. 

PMID- 24039929
TI  - Grape extracts inhibit multiple events in the cell biology of cholera
      intoxication.
AB  - Vibrio cholerae produces cholera toxin (CT), an AB5 protein toxin that is
      primarily responsible for the profuse watery diarrhea of cholera. CT is secreted
      into the extracellular milieu, but the toxin attacks its Gsalpha target within
      the cytosol of a host cell. Thus, CT must cross a cellular membrane barrier in
      order to function. This event only occurs after the toxin travels by retrograde
      vesicular transport from the cell surface to the endoplasmic reticulum (ER). The
      catalytic A1 polypeptide then dissociates from the rest of the toxin and assumes
      an unfolded conformation that facilitates its transfer to the cytosol by a
      process involving the quality control system of ER-associated degradation.
      Productive intoxication is blocked by alterations to the vesicular transport of
      CT and/or the ER-to-cytosol translocation of CTA1. Various plant compounds have
      been reported to inhibit the cytopathic activity of CT, so in this work we
      evaluated the potential anti-CT properties of grape extract. Two grape extracts
      currently sold as nutritional supplements inhibited CT and Escherichia coli heat
      labile toxin activity against cultured cells and intestinal loops. CT
      intoxication was blocked even when the extracts were added an hour after the
      initial toxin exposure. A specific subset of host-toxin interactions involving
      both the catalytic CTA1 subunit and the cell-binding CTB pentamer were affected.
      The extracts blocked toxin binding to the cell surface, prevented unfolding of
      the isolated CTA1 subunit, inhibited CTA1 translocation to the cytosol, and
      disrupted the catalytic activity of CTA1. Grape extract could thus potentially
      serve as a novel therapeutic to prevent or possibly treat cholera. 

PMID- 24039930
TI  - Within-population genetic structure in beech (Fagus sylvatica L.) stands
      characterized by different disturbance histories: does forest management simplify
      population substructure?
AB  - The fine-scale assessment of both spatially and non-spatially distributed genetic
      variation is crucial to preserve forest genetic resources through appropriate
      forest management. Cryptic within-population genetic structure may be more common
      than previously thought in forest tree populations, which has strong implications
      for the potential of forests to adapt to environmental change. The present study
      was aimed at comparing within-population genetic structure in European beech
      (Fagus sylvatica L.) plots experiencing different disturbance levels. Five plot
      pairs made up by disturbed and undisturbed plots having the same biogeographic
      history were sampled throughout Europe. Overall, 1298 individuals were analyzed
      using four highly polymorphic nuclear microsatellite markers (SSRs). Bayesian
      clustering within plots identified 3 to 11 genetic clusters (within-plot theta ST
      ranged from 0.025 to 0.124). The proportion of within-population genetic
      variation due to genetic substructuring (F CluPlot = 0.067) was higher than the
      differentiation among the 10 plots (F PlotTot = 0.045). Focusing on the
      comparison between managed and unmanaged plots, disturbance mostly explains
      differences in the complexity of within-population genetic structure, determining
      a reduction of the number of genetic clusters present in a standardized area. Our
      results show that: i) genetic substructuring needs to be investigated when
      studying the within-population genetic structure in forest tree populations, and
      ii) indices describing subtle characteristics of the within-population genetic
      structure are good candidates for providing early signals of the consequences of
      forest management, and of disturbance events in general. 

PMID- 24039931
TI  - Modeling the intra- and extracellular cytokine signaling pathway under heat
      stroke in the liver.
AB  - Heat stroke (HS) is a life-threatening illness induced by prolonged exposure to a
      hot environment that causes central nervous system abnormalities and severe
      hyperthermia. Current data suggest that the pathophysiological responses to heat
      stroke may not only be due to the immediate effects of heat exposure per se but
      also the result of a systemic inflammatory response syndrome (SIRS). The
      observation that pro- (e.g., IL-1) and anti-inflammatory (e.g., IL-10) cytokines
      are elevated concomitantly during recovery suggests a complex network of
      interactions involved in the manifestation of heat-induced SIRS. In this study,
      we measured a set of circulating cytokine/soluble cytokine receptor proteins and
      liver cytokine and receptor mRNA accumulation in wild-type and tumor necrosis
      factor (TNF) receptor knockout mice to assess the effect of neutralization of TNF
      signaling on the SIRS following HS. Using a systems approach, we developed a
      computational model describing dynamic changes (intra- and extracellular events)
      in the cytokine signaling pathways in response to HS that was fitted to novel
      genomic (liver mRNA accumulation) and proteomic (circulating cytokines and
      receptors) data using global optimization. The model allows integration of
      relevant biological knowledge and formulation of new hypotheses regarding the
      molecular mechanisms behind the complex etiology of HS that may serve as future
      therapeutic targets. Moreover, using our unique modeling framework, we explored
      cytokine signaling pathways with three in silico experiments (e.g. by simulating
      different heat insult scenarios and responses in cytokine knockout strains in
      silico). 

PMID- 24039932
TI  - Blood pressure gradients and cardiovascular risk factors in urban and rural
      populations in Abia State South Eastern Nigeria using the WHO STEPwise approach.
AB  - BACKGROUND: Developing countries of sub-Saharan Africa (SSA) face a double burden
      of non-communicable diseases (NCDs) and communicable diseases. As high blood
      pressure (BP) is a common global cardiovascular (CV) disorder associated with
      high morbidity and mortality, the relationship between gradients of BP and other
      CV risk factors was assessed in Abia State, Nigeria. METHODS: Using the WHO
      STEPwise approach to surveillance of chronic disease risk factors, we conducted a
      population-based cross-sectional survey in Abia state, Nigeria from August 2011
      to March 2012. Data collected at various steps included: demographic and
      behavioral risk factors (Step 1); BP and anthropometric measurements (Step 2),
      and fasting blood cholesterol and glucose (Step 3). RESULTS: Of the 2983 subjects
      with complete data for analysis, 52.1% were females and 53.2% were rural
      dwellers. Overall, the distribution of selected CV disease risk factors was
      diabetes (3.6%), hypertension (31.4%), cigarette smoking (13.3%), use of
      smokeless tobacco (4.8%), physical inactivity (64.2%) and being overweight or
      obese (33.7%). Presence of hypertension, excessive intake of alcohol, smoking
      (cigarette and smokeless tobacco) and physical inactivity occurred more
      frequently in males than in females (p<0.05); while low income, lack of any
      formal education and use of smokeless tobacco were seen more frequently in rural
      dwellers than in those living in urban areas (p<0.05). The frequency of selected
      CV risk factors increased as BP was graded from optimal, normal to hypertension;
      and high BP correlated with age, gender, smokeless tobacco, overweight or
      obesity, annual income and level of education. CONCLUSION: Given the high
      prevalence of hypertension in this part of Nigeria, there is an urgent need to
      focus on the reduction of preventable CV risk factors we have observed to be
      associated with hypertension, in order to effectively reduce the burden of NCDs
      in Africa.

PMID- 24039933
TI  - Effects of indoleamine 2,3-dioxygenase deficiency on high-fat diet-induced
      hepatic inflammation.
AB  - Hepatic immune regulation is associated with the progression from simple
      steatosis to non-alcoholic steatohepatitis, a severe condition of inflamed fatty
      liver. Indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme that mediates
      the catabolism of L-tryptophan to L-kynurenine, plays an important role in
      hepatic immune regulation. In the present study, we examined the effects of IDO
      gene silencing on high-fat diet (HFD)-induced liver inflammation and fibrosis in
      mice. After being fed a HFD for 26 weeks, the IDO-knockout (KO) mice showed a
      marked infiltration of inflammatory cells, especially macrophages and T
      lymphocytes, in the liver. The expression levels of F4/80, IFNgamma, IL-1beta,
      and IL-6 mRNA in the liver and the expression levels of F4/80 and TNF-alpha mRNA
      in the white adipose tissue were significantly increased in IDO-KO mice, although
      hepatic steatosis, the accumulation of intrahepatic triglycerides, and the amount
      of oxidative stress were lower than those in IDO-wild-type mice. IDO-KO mice also
      developed marked pericellular fibrosis in the liver, accumulated hepatic
      hydroxyproline, and exhibited increased expression levels of hepatic TGF-beta1
      mRNA. These findings suggest that IDO-KO renders the mice more susceptible to HFD
      induced hepatic inflammation and fibrosis. Therefore, IDO may have a protective
      effect against hepatic fibrosis, at least in this HFD-induced liver injury model.

PMID- 24039934
TI  - Inhibition of type I insulin-like growth factor receptor signaling attenuates the
      development of breast cancer brain metastasis.
AB  - Brain metastasis is a common cause of mortality in cancer patients, yet potential
      therapeutic targets remain largely unknown. The type I insulin-like growth factor
      receptor (IGF-IR) is known to play a role in the progression of breast cancer and
      is currently being investigated in the clinical setting for various types of
      cancer. The present study demonstrates that IGF-IR is constitutively
      autophosphorylated in brain-seeking breast cancer sublines. Knockdown of IGF-IR
      results in a decrease of phospho-AKT and phospho-p70s6k, as well as decreased
      migration and invasion of MDA-MB-231Br brain-seeking cells. In addition,
      transient ablation of IGFBP3, which is overexpressed in brain-seeking cells,
      blocks IGF-IR activation. Using an in vivo experimental brain metastasis model,
      we show that IGF-IR knockdown brain-seeking cells have reduced potential to
      establish brain metastases. Finally, we demonstrate that the malignancy of brain
      seeking cells is attenuated by pharmacological inhibition with picropodophyllin,
      an IGF-IR-specific tyrosine kinase inhibitor. Together, our data suggest that the
      IGF-IR is an important mediator of brain metastasis and its ablation delays the
      onset of brain metastases in our model system. 

PMID- 24039935
TI  - Effects of upconversion nanoparticles on polymerase chain reaction.
AB  - Nanoparticles (NPs) are attractive materials owing to their physical and
      electrochemical properties, which make them extremely useful in diagnostic
      applications. Photon upconversion is the phenomenon where high-energy photons are
      emitted upon excitation of low-energy photons. Nucleic acids detection based on
      upconversion nanoparticles (UCNPs), which display a high signal-to-noise ratio
      and no photobleaching, has been widely applied. We evaluated whether UCNPs can
      improve polymerase chain reaction (PCR) specificity and affect PCR amplification.
      The effects of UCNPs with a diameter size of 40, 70, and 250 nm were evaluated
      using 3 PCR kits (AccuPower PCR PreMix, AmpliTaq Gold 360 Master Mix, and
      HotStarTaq Plus Master Mix) and 3 real-time PCR kits (AccuPower GreenStar qPCR
      PreMix, SYBR Green PCR Master Mix, and QuantiTect SYBR Green PCR Kit). Quantum
      dots were used for comparison with the UCNPs. In the presence of an appropriate
      concentration of UCNPs, PCR specificity was optimized. UCNPs of 40-nm size
      improved PCR specificity more effectively than did UCNPs sized 70 or 250 nm. As
      the size and concentrations of the UCNPs were increased, PCR amplification was
      more severely inhibited. At lower annealing temperatures (25 degrees C-45 degrees
      C), addition of the 40 nm UCNP (1 ug/uL) to the PCR reagent produced specific PCR
      products without nonspecific sequence amplification. Therefore, UCNPs of
      different sizes, with different DNA polymerases used in the commercial kits,
      showed different inhibitory effects on PCR amplification. These results
      demonstrate that optimization of UCNPs, added to reaction mixtures at appropriate
      concentrations, can improve PCR specificity. However, the mechanism underlining
      UCNPs effect on PCR remains unclear and will require further investigation. 

PMID- 24039936
TI  - A network-based method to assess the statistical significance of mild co
      regulation effects.
AB  - Recent development of high-throughput, multiplexing technology has initiated
      projects that systematically investigate interactions between two types of
      components in biological networks, for instance transcription factors and
      promoter sequences, or microRNAs (miRNAs) and mRNAs. In terms of network biology,
      such screening approaches primarily attempt to elucidate relations between
      biological components of two distinct types, which can be represented as edges
      between nodes in a bipartite graph. However, it is often desirable not only to
      determine regulatory relationships between nodes of different types, but also to
      understand the connection patterns of nodes of the same type. Especially
      interesting is the co-occurrence of two nodes of the same type, i.e., the number
      of their common neighbours, which current high-throughput screening analysis
      fails to address. The co-occurrence gives the number of circumstances under which
      both of the biological components are influenced in the same way. Here we present
      SICORE, a novel network-based method to detect pairs of nodes with a
      statistically significant co-occurrence. We first show the stability of the
      proposed method on artificial data sets: when randomly adding and deleting
      observations we obtain reliable results even with noise exceeding the expected
      level in large-scale experiments. Subsequently, we illustrate the viability of
      the method based on the analysis of a proteomic screening data set to reveal
      regulatory patterns of human microRNAs targeting proteins in the EGFR-driven cell
      cycle signalling system. Since statistically significant co-occurrence may
      indicate functional synergy and the mechanisms underlying canalization, and thus
      hold promise in drug target identification and therapeutic development, we
      provide a platform-independent implementation of SICORE with a graphical user
      interface as a novel tool in the arsenal of high-throughput screening analysis. 

PMID- 24039937
TI  - A floating bridge disrupts seaward migration and increases mortality of steelhead
      smolts in Hood Canal, Washington state.
AB  - BACKGROUND: Habitat modifications resulting from human transportation and power
      generation infrastructure (e.g., roads, dams, bridges) can impede movement and
      alter natural migration patterns of aquatic animal populations, which may
      negatively affect survival and population viability. Full or partial barriers are
      especially problematic for migratory species whose life histories hinge on
      habitat connectivity. METHODOLOGY/PRINCIPAL FINDINGS: The Hood Canal Bridge, a
      floating structure spanning the northern outlet of Hood Canal in Puget Sound,
      Washington, extends 3.6 meters underwater and forms a partial barrier for
      steelhead migrating from Hood Canal to the Pacific Ocean. We used acoustic
      telemetry to monitor migration behavior and mortality of steelhead smolts passing
      four receiver arrays and several single receivers within the Hood Canal, Puget
      Sound, and Strait of Juan de Fuca. Twenty-seven mortality events were detected
      within the vicinity of the Hood Canal Bridge, while only one mortality was
      recorded on the other 325 receivers deployed throughout the study area. Migrating
      steelhead smolts were detected at the Hood Canal Bridge array with greater
      frequency, on more receivers, and for longer durations than smolts migrating past
      three comparably configured arrays. Longer migration times and paths are likely
      to result in a higher density of smolts near the bridge in relation to other
      sites along the migration route, possibly inducing an aggregative predator
      response to steelhead smolts. CONCLUSIONS/SIGNIFICANCE: This study provides
      strong evidence of substantial migration interference and increased mortality
      risk associated with the Hood Canal Bridge, and may partially explain low early
      marine survival rates observed in Hood Canal steelhead populations. Understanding
      where habitat modifications indirectly increase predation pressures on threatened
      populations helps inform potential approaches to mitigation.

PMID- 24039938
TI  - In vitro infection of pupae with Israeli acute paralysis virus suggests
      disturbance of transcriptional homeostasis in honey bees (Apis mellifera).
AB  - The ongoing decline of honey bee health worldwide is a serious economic and
      ecological concern. One major contributor to the decline are pathogens, including
      several honey bee viruses. However, information is limited on the biology of bee
      viruses and molecular interactions with their hosts. An experimental protocol to
      test these systems was developed, using injections of Israeli Acute Paralysis
      Virus (IAPV) into honey bee pupae reared ex-situ under laboratory conditions. The
      infected pupae developed pronounced but variable patterns of disease. Symptoms
      varied from complete cessation of development with no visual evidence of disease
      to rapid darkening of a part or the entire body. Considerable differences in IAPV
      titer dynamics were observed, suggesting significant variation in resistance to
      IAPV among and possibly within honey bee colonies. Thus, selective breeding for
      virus resistance should be possible. Gene expression analyses of three separate
      experiments suggest IAPV disruption of transcriptional homeostasis of several
      fundamental cellular functions, including an up-regulation of the ribosomal
      biogenesis pathway. These results provide first insights into the mechanisms of
      IAPV pathogenicity. They mirror a transcriptional survey of honey bees afflicted
      with Colony Collapse Disorder and thus support the hypothesis that viruses play a
      critical role in declining honey bee health. 

PMID- 24039939
TI  - Conservation actions based on red lists do not capture the functional and
      phylogenetic diversity of birds in Brazil.
AB  - Red Lists of threatened species play a critical role in conservation science and
      practice. However, policy-making based on Red Lists ignores ecological and
      evolutionary consequences of losing biodiversity because these lists focus on
      species alone. To decide if relying on Red Lists alone can help to conserve
      communities' functional (FD) and phylogenetic (PD) diversity, it is useful to
      evaluate whether Red List categories represent species with diverse ecological
      traits and evolutionary histories. Additionally, local scale analyses using
      regional Red Lists should represent more realistic pools of co-occurring species
      and thereby better capture eventual losses of FD and PD. Here, we used 21 life
      history traits and a phylogeny for all Brazilian birds to determine whether
      species assigned under the IUCN global Red List, the Brazilian national, and
      regional Red Lists capture more FD and PD than expected by chance. We also built
      local Red Lists and analysed if they capture more FD and PD at the local scale.
      Further, we investigated whether individual threat categories have species with
      greater FD and PD than expected by chance. At any given scale, threat categories
      did not capture greater FD or PD than expected by chance. Indeed, mostly
      categories captured equal or less FD or PD than expected by chance. These
      findings would not have great consequences if Red Lists were not often considered
      as a major decision support tool for policy-making. Our results challenge the
      practice of investing conservation resources based only on species Red Lists
      because, from an ecological and evolutionary point of view, this would be the
      same as protecting similar or random sets of species. Thus, new prioritization
      methods, such as the EDGE of Existence initiative, should be developed and
      applied to conserve species' ecological traits and evolutionary histories at
      different spatial scales. 

PMID- 24039940
TI  - Genome wide transcriptome analysis of dendritic cells identifies genes with
      altered expression in psoriasis.
AB  - Activation of dendritic cells by different pathogens induces the secretion of
      proinflammatory mediators resulting in local inflammation. Importantly, innate
      immunity must be properly controlled, as its continuous activation leads to the
      development of chronic inflammatory diseases such as psoriasis.
      Lipopolysaccharide (LPS) or peptidoglycan (PGN) induced tolerance, a phenomenon
      of transient unresponsiveness of cells to repeated or prolonged stimulation,
      proved valuable model for the study of chronic inflammation. Thus, the aim of
      this study was the identification of the transcriptional diversity of primary
      human immature dendritic cells (iDCs) upon PGN induced tolerance. Using SAGE-Seq
      approach, a tag-based transcriptome sequencing method, we investigated gene
      expression changes of primary human iDCs upon stimulation or restimulation with
      Staphylococcus aureus derived PGN, a widely used TLR2 ligand. Based on the
      expression pattern of the altered genes, we identified non-tolerizeable and
      tolerizeable genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and
      Genomes (Kegg) analysis showed marked enrichment of immune-, cell cycle- and
      apoptosis related genes. In parallel to the marked induction of proinflammatory
      mediators, negative feedback regulators of innate immunity, such as TNFAIP3,
      TNFAIP8, Tyro3 and Mer are markedly downregulated in tolerant cells. We also
      demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is altered in
      both lesional, and non-lesional skin of psoriatic patients. Finally, we show that
      pretreatment of immature dendritic cells with anti-TNF-alpha inhibits the
      expression of IL-6 and CCL1 in tolerant iDCs and partially releases the
      suppression of TNFAIP8. Our findings suggest that after PGN
      stimulation/restimulation the host cell utilizes different mechanisms in order to
      maintain critical balance between inflammation and tolerance. Importantly, the
      transcriptome sequencing of stimulated/restimulated iDCs identified numerous
      genes with altered expression to date not associated with role in chronic
      inflammation, underlying the relevance of our in vitro model for further
      characterization of IFN-primed iDCs. 

PMID- 24039941
TI  - Simulated estimates of pre-pregnancy and gestational diabetes mellitus in the US:
      1980 to 2008.
AB  - PURPOSE: To simulate national estimates of prepregnancy and gestational diabetes
      mellitus (GDM) in non-Hispanic white (NHW) and non-Hispanic black (NHB) women.
      METHODS: Prepregnancy diabetes and GDM were estimated as a function of age,
      race/ethnicity, and body mass index (BMI) using South Carolina live singleton
      births from 2004-2008. Diabetes risk was applied to a simulated population. Age,
      natality and BMI were assigned to women according to race- and age-specific US
      Census, Natality and National Health and Nutrition Examination Surveys (NHANES)
      data, respectively. RESULTS: From 1980-2008, estimated GDM prevalence increased
      from 4.11% to 6.80% [2.68% (95% CI 2.58%-2.78%)] and from 3.96% to 6.43% [2.47%
      (95% CI 2.39%-2.55%)] in NHW and NHB women, respectively. In NHW women
      prepregnancy diabetes prevalence increased 0.90% (95% CI 0.85%-0.95%) from 0.95%
      in 1980 to 1.85% in 2008. In NHB women from 1980 through 2008 estimated
      prepregnancy diabetes prevalence increased 1.51% (95% CI 1.44%-1.57%), from 1.66%
      to 3.16%. CONCLUSIONS: Racial disparities in diabetes prevalence during pregnancy
      appear to stem from a higher prevalence of prepregnancy diabetes, but not GDM, in
      NHB than NHW.

PMID- 24039942
TI  - Analyzing the modification of the Shewanella oneidensis MR-1 flagellar filament.
AB  - The unsheathed flagellar filament of Shewanella oneidensis MR-1 is composed of
      two highly homologous flagellins, FlaA, and the major structural unit, FlaB. We
      identified a gene cluster, SO_3261-SO_3265 (now sfmABCDE), that is required for
      the formation of a fully functional filament and for motility. The predicted
      function of the corresponding gene products strongly indicated a role in
      flagellin modification. Accordingly, loss of sfmABCDE results in a significant
      mass shift of both FlaA and FlaB. Mass spectroscopy analysis and single residue
      substitutions identified five serine residues in both flagellins that are
      modified via O-linkage. Modeling of the flagellin structures strongly suggests
      that at least four of the modified residues are exposed to the filament's
      surface. However, none of the five serine residues solely is crucial for function
      and assembly. Structural analysis of the flagellin modification revealed that it
      likely contains a nonulosonic acid (274 Da) linked to each glycosylated serine.
      The putative nonulosonic acid is further substituted with a 236 Da moiety which
      can carry additional methyl groups (250 Da, 264 Da). In addition, at least 5
      lysine residues in FlaB and one in FlaA were found to be methylated. Based on
      homology comparisons we suggest that smfABCDE is required for species-specific
      flagellin modification in S. oneidensis MR-1. 

PMID- 24039943
TI  - Topographical body fat distribution links to amino acid and lipid metabolism in
      healthy obese women [corrected].
AB  - Visceral adiposity is increasingly recognized as a key condition for the
      development of obesity related disorders, with the ratio between visceral adipose
      tissue (VAT) and subcutaneous adipose tissue (SAT) reported as the best correlate
      of cardiometabolic risk. In this study, using a cohort of 40 obese females (age:
      25-45 y, BMI: 28-40 kg/m(2)) under healthy clinical conditions and monitored over
      a 2 weeks period we examined the relationships between different body composition
      parameters, estimates of visceral adiposity and blood/urine metabolic profiles.
      Metabonomics and lipidomics analysis of blood plasma and urine were employed in
      combination with in vivo quantitation of body composition and abdominal fat
      distribution using iDXA and computerized tomography. Of the various visceral fat
      estimates, VAT/SAT and VAT/total abdominal fat ratios exhibited significant
      associations with regio-specific body lean and fat composition. The integration
      of these visceral fat estimates with metabolic profiles of blood and urine
      described a distinct amino acid, diacyl and ether phospholipid phenotype in women
      with higher visceral fat. Metabolites important in predicting visceral fat
      adiposity as assessed by Random forest analysis highlighted 7 most robust
      markers, including tyrosine, glutamine, PC-O 44?6, PC-O 44?4, PC-O 42?4, PC-O
      40?4, and PC-O 40?3 lipid species. Unexpectedly, the visceral fat associated
      inflammatory profiles were shown to be highly influenced by inter-days and
      between-subject variations. Nevertheless, the visceral fat associated amino acid
      and lipid signature is proposed to be further validated for future patient
      stratification and cardiometabolic health diagnostics. 

PMID- 24039944
TI  - Use of the metastatic lymph node ratio to evaluate the prognosis of esophageal
      cancer patients with node metastasis following radical esophagectomy.
AB  - OBJECTIVES: The objective of this study was to investigate the number of
      metastatic lymph nodes (pN) and the metastatic lymph node ratio (MLR) on the post
      surgical prognosis of Chinese patients with esophageal cancer (EC) and lymph node
      metastasis. METHODS: We enrolled 353 patients who received primary curative
      resection for EC from 1990 to 2003. The association of pN and MLR with 5-year
      overall survival (OS) was examined by receiver operating characteristic (ROC) and
      area under the curve (AUC) analysis. The Kaplan-Meier method was used to
      calculate survival rates, and survival curves were compared with the log-rank
      test. The Cox model was employed for univariate and multivariate analyses of
      factors associated with 5-year OS. RESULTS: The median follow-up time was 41
      months, and the 1-, 3- and 5-year OS rates were 71.2%, 30.4%, and 19.5%,
      respectively. Univariate analysis showed that age, pN stage, and the MLR were
      prognostic factors for OS. Patients with MLRs less than 0.15, MLRs of 0.15-0.30,
      and MLRs greater than 0.30 had 5-year OS rates of 30.1%, 17.8%, and 9.5%,
      respectively (p < 0.001). Patients classified as pN1, pN2, and pN3 had 5-year OS
      rates of 23.7%, 11.4%, and 9.9%, respectively (p < 0.001). Multivariate analysis
      indicated that a high MLR and advanced age were significant and independent risk
      factors for poor OS. Patients classified as pN2 had significantly worse OS than
      those classified as pN1 (p = 0.022), but those classified as pN3 had similar OS
      as those classified as pN1 (p = 0.166). ROC analysis indicated that MLR (AUC =
      0.585, p = 0.016) had better predictive value than pN (AUC = 0.565, p = 0.068).
      CONCLUSIONS: The integrated use of MLR and pN may be suitable for evaluation of
      OS in Chinese patients with EC and positive nodal metastasis after curative
      resection.

PMID- 24039945
TI  - DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk: a meta
      analysis.
AB  - BACKGROUND AND OBJECTIVE: The X-ray repair cross-complementing group 1 (XRCC1)
      protein plays a crucial role in base excision repair (BER) pathway by acting as a
      scaffold for other BER enzymes. Variants in the XRCC1 gene might alter protein
      structure or function or create alternatively spliced proteins which may
      influence BER efficiency and hence affect individual susceptibility to bladder
      cancer. Recent epidemiological studies have shown inconsistent associations
      between these polymorphisms and bladder cancer. To clarify the situation, a
      comprehensive meta-analysis of all available studies was performed in this study.
      METHODS: PubMed, EMBASE, and Chinese Biomedical Literature database (CBM)
      databases have been systematically searched to identify all relevant studies for
      the period up to February 2013. Data were abstracted independently by two
      reviewers and Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated. Subgroup analyses were performed mainly by ethnicity and smoking
      status. RESULTS: A total of 26 case-control studies, including 24 studies for
      R399Q polymorphism, 15 studies for R194W polymorphism, and 7 studies for R280H
      polymorphism met the inclusion criteria and were selected. With respect to R399Q
      polymorphism, significantly decreased bladder cancer risk was found among smokers
      (AA vs. GG: OR=0.693, 95%CI= 0.515-0.932, P=0.015 and recessive model AA vs.
      GA+GG: OR=0.680, 95%CI= 0.515-0.898, P=0.007, respectively). With respect to
      R194W and R280H polymorphism, significantly increased bladder cancer risk were
      observed among Asians (TT+CT vs. CC:OR = 1.327, 95% CI 1.086-1.622, P=0.006 for
      R194W, and AA+GA vs. GG: OR=2.094, 95% CI 1.211-3.621, P=0.008 for R280H,
      respectively). CONCLUSIONS: This meta-analysis suggests that the XRCC1 R399Q
      polymorphism may play a protective role against bladder cancer among smokers.
      However, the XRCC1 R194W and R280H polymorphisms were both associated with
      increased bladder cancer risk among Asians. Further studies with larger sample
      sizes are needed to validate our finds.

PMID- 24039946
TI  - Improved leptin sensitivity as a potential candidate responsible for the
      spontaneous food restriction of the Lou/C rat.
AB  - The Lou/C rat, an inbred strain of Wistar origin, was described as a model of
      resistance to age- and diet-induced obesity. Although such a resistance involves
      many metabolic parameters described in our previous studies, Lou/C rats also
      exhibit a spontaneous food restriction due to decreased food consumption during
      the nocturnal period. We then attempted to delineate the leptin sensitivity and
      mechanisms implicated in this strain, using different protocols of acute central
      and peripheral leptin administration. A first analysis of the meal patterns
      revealed that Lou/C rats eat smaller meals, without any change in meal number
      compared to age-matched Wistar animals. Although the expression of the recognized
      leptin transporters (leptin receptors and megalin) measured in the choroid plexus
      was normal in Lou/C rats, the decreased triglyceridemia observed in these animals
      is compatible with an increased leptin transport across the blood brain barrier.
      Improved hypothalamic leptin signaling in Lou/C rats was also suggested by the
      higher pSTAT3/STAT3 (signal transducer and activator of transcription 3) ratio
      observed following acute peripheral leptin administration, as well as by the
      lower hypothalamic mRNA expression of the suppressor of cytokine signaling 3
      (SOCS3), known to downregulate leptin signaling. To conclude, spontaneous
      hypophagia of Lou/C rats appears to be related to improved leptin sensitivity.
      The main mechanism underlying such a phenomenon consists in improved leptin
      signaling through the Ob-Rb leptin receptor isoform, which seems to consequently
      lead to overexpression of brain-derived neurotrophic factor (BDNF) and
      thyrotropin-releasing hormone (TRH). 

PMID- 24039947
TI  - Limited impact of passive non-neutralizing antibody immunization in acute SIV
      infection on viremia control in rhesus macaques.
AB  - BACKGROUND: Antiviral antibodies, especially those with neutralizing activity
      against the incoming strain, are potentially important immunological effectors to
      control human immunodeficiency virus (HIV) infection. While neutralizing activity
      appears to be central in sterile protection against HIV infection, the entity of
      inhibitory mechanisms via HIV and simian immunodeficiency virus (SIV)-specific
      antibodies remains elusive. The recent HIV vaccine trial RV144 and studies in
      nonhuman primate models have indicated controversial protective efficacy of
      HIV/SIV-specific non-neutralizing binding antibodies (non-NAbs). While reports on
      HIV-specific non-NAbs have demonstrated virus inhibitory activity in vitro,
      whether non-NAbs could also alter the pathogenic course of established SIV
      replication in vivo, likewise via neutralizing antibody (NAb) administration, has
      been unclear. Here, we performed post-infection passive immunization of SIV
      infected rhesus macaques with polyclonal SIV-specific, antibody-dependent cell
      mediated viral inhibition (ADCVI)-competent non-NAbs. METHODS AND FINDINGS: Ten
      lots of polyclonal immunoglobulin G (IgG) were prepared from plasma of ten
      chronically SIVmac239-infected, NAb-negative rhesus macaques, respectively. Their
      binding capacity to whole SIVmac239 virions showed a propensity similar to ADCVI
      activity. A cocktail of three non-NAb lots showing high virion-binding capacity
      and ADCVI activity was administered to rhesus macaques at day 7 post-SIVmac239
      challenge. This resulted in an infection course comparable with control animals,
      with no significant difference in set point plasma viral loads or immune
      parameters. CONCLUSIONS: Despite virus-specific suppressive activity of the non
      NAbs having been observed in vitro, their passive immunization post-infection did
      not result in SIV control in vivo. Virion binding and ADCVI activity with lack of
      virus neutralizing activity were indicated to be insufficient for antibody
      triggered non-sterile SIV control. More diverse effector functions or
      sophisticated localization may be required for non-NAbs to impact HIV/SIV
      replication in vivo.

PMID- 24039948
TI  - Detection of Bacillus anthracis DNA in complex soil and air samples using next
      generation sequencing.
AB  - Bacillus anthracis is the potentially lethal etiologic agent of anthrax disease,
      and is a significant concern in the realm of biodefense. One of the cornerstones
      of an effective biodefense strategy is the ability to detect infectious agents
      with a high degree of sensitivity and specificity in the context of a complex
      sample background. The nature of the B. anthracis genome, however, renders
      specific detection difficult, due to close homology with B. cereus and B.
      thuringiensis. We therefore elected to determine the efficacy of next-generation
      sequencing analysis and microarrays for detection of B. anthracis in an
      environmental background. We applied next-generation sequencing to titrated
      genome copy numbers of B. anthracis in the presence of background nucleic acid
      extracted from aerosol and soil samples. We found next-generation sequencing to
      be capable of detecting as few as 10 genomic equivalents of B. anthracis DNA per
      nanogram of background nucleic acid. Detection was accomplished by mapping reads
      to either a defined subset of reference genomes or to the full GenBank database.
      Moreover, sequence data obtained from B. anthracis could be reliably
      distinguished from sequence data mapping to either B. cereus or B. thuringiensis.
      We also demonstrated the efficacy of a microbial census microarray in detecting
      B. anthracis in the same samples, representing a cost-effective and high
      throughput approach, complementary to next-generation sequencing. Our results, in
      combination with the capacity of sequencing for providing insights into the
      genomic characteristics of complex and novel organisms, suggest that these
      platforms should be considered important components of a biosurveillance
      strategy. 

PMID- 24039949
TI  - Lipopolysaccharide-induced weakness in the preterm diaphragm is associated with
      mitochondrial electron transport chain dysfunction and oxidative stress.
AB  - Diaphragmatic contractility is reduced in preterm lambs after lipopolysaccharide
      (LPS) exposure in utero. The mechanism of impaired fetal diaphragm contractility
      after LPS exposure is unknown. We hypothesise that in utero exposure to LPS
      induces a deficiency of mitochondrial complex activity and oxidative damage in
      the fetal diaphragm. To test this hypothesis, we used a well-established preterm
      ovine model of chorioamnionitis: Pregnant ewes received intra-amniotic (IA)
      saline or 10 mg LPS, at 2 d or 7 d prior to surgical delivery at 121 d GA (term =
      150 d). The fetus was killed humanely immediately after delivery for tissue
      sampling. Mitochondrial fractions were prepared from the isolated diaphragm and
      mitochondrial electron transfer chain activities were evaluated using enzymatic
      assays. Oxidative stress was investigated by quantifying mitochondrial oxidative
      protein levels and determining antioxidant gene and protein (catalase, superoxide
      dismutase 2 and glutathione peroxidase 1) expression. The activity of the
      erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signalling pathway was
      examined by quantifying the Nrf2 protein content of cell lysate and nuclear
      extract. A 2 d LPS exposure in utero significantly decreased electron transfer
      chain complex II and IV activity (p<0.05). A 7 d LPS exposure inhibited
      superoxide dismutase 2 and catalase expression at gene and protein levels, and
      Nrf2 pathway activity (p<0.05) compared with control and 2 d LPS groups,
      respectively. Diaphragm mitochondria accumulated oxidised protein after a 7 d LPS
      exposure. We conclude that intrauterine exposure to LPS induces mitochondrial
      oxidative stress and electron chain dysfunction in the fetal diaphragm, that is
      further exacerbated by impairment of the antioxidant signalling pathway and
      decreased antioxidant activity. 

PMID- 24039950
TI  - Psychological interventions for patients with coronary heart disease and their
      partners: a systematic review.
AB  - OBJECTIVES: Despite evidence that patients with coronary heart disease (CHD) and
      their partners report significant psychological distress, and suggestions that
      involving partners in interventions alleviates such distress, no systematic
      reviews have examined this. The objective of this study was to systematically
      review evidence on the effectiveness of psychological interventions for patients
      with CHD and their partners. METHODS: CENTRAL, Medline, EMBASE, CINAHL and
      PsycINFO databases were searched through October 2012. Randomized controlled
      trials evaluating psychological interventions for patients with CHD and their
      partners were included. Selection of studies, study appraisal, data extraction
      and analysis were undertaken using standard methods. RESULTS: Seven studies
      comprising 673 participants were included, two of which indicated that
      psychological interventions result in modest improvements in patients' depressive
      symptoms, anxiety, knowledge of disease and treatment, and satisfaction with
      care, and in partners' anxiety, knowledge and satisfaction. In partners, there
      was a non-significant trend for improvements in depressive symptoms. One study
      showed a beneficial effect on blood pressure. There was no evidence of a
      significant effect on mortality, morbidity or cardiovascular risk factors for
      patients or social support for patients and partner. CONCLUSIONS: The small
      number of studies included in the review had generally poor methodology, as shown
      by the risk of bias, and were performed over 10 years ago. As only two of the
      seven studies resulted in modest improvements in outcomes, no firm conclusions
      can be drawn as to the effectiveness of such interventions in this population.

PMID- 24039951
TI  - Epigallocatechin-3-gallate inhibits stem-like inflammatory breast cancer cells.
AB  - Inflammatory Breast Cancer (IBC) is a highly aggressive form of cancer
      characterized by high rates of proliferation, lymphangiogenesis and metastasis,
      and an overall poor survival. As regular green tea consumption has been
      associated with improved prognosis of breast cancer patients, including decreased
      risk of recurrence, here the effects of the green tea polyphenol epigallocatechin
      3-gallate (EGCG) were tested on two IBC lines: SUM-149 and SUM-190. EGCG
      decreased expression of genes that promote proliferation, migration, invasion,
      and survival. Consistently, growth, invasive properties, and survival of IBC
      cells were reduced by EGCG treatment. EGCG also reduced lymphangiogenesis
      promoting genes, in particular VEGF-D. Conditioned media from EGCG-treated IBC
      cells displayed decreased VEGF-D secretion and reduced ability to promote
      lymphangiogenesis in vitro as measured by hTERT-HDLEC lymphatic endothelial cell
      migration and tube formation. Tumorsphere formation by SUM-149 cells was robustly
      inhibited by EGCG, suggesting effects on self-renewal ability. Stem-like SUM-149
      cells with high aldehyde dehydrogenase (ALDH) activity, previously implicated in
      poor patient prognosis, were isolated. EGCG treatment reduced growth and induced
      apoptosis of the stem-like SUM-149 cells in culture. In an orthotopic mouse
      model, EGCG decreased growth of pre-existing tumors derived from ALDH-positive
      stem-like SUM-149 cells and their expression of VEGF-D, which correlated with a
      significant decrease in peritumoral lymphatic vessel density. Thus, EGCG inhibits
      the overall aggressive IBC phenotype. Reduction of the stem-like cell compartment
      by EGCG may explain the decreased risk of breast cancer recurrence among green
      tea drinkers. Recent clinical trials demonstrate the efficacy of green tea
      polyphenol extracts in treatment of prostate cancer and lymphocytic leukemia with
      low toxicity. Given the poor prognosis of IBC patients, our findings suggest
      further exploration of EGCG or green tea in combinatorial treatments against
      active IBC disease or in maintenance regimens to avoid recurrence is warranted. 

PMID- 24039952
TI  - CysLT(1)R antagonists inhibit tumor growth in a xenograft model of colon cancer.
AB  - The expression of the inflammatory G-protein coupled receptor CysLT1R has been
      shown to be upregulated in colon cancer patients and associated with poor
      prognosis. The present study investigated the correlation between CysLT1R and
      colon cancer development in vivo using CysLT1R antagonists (ZM198,615 or
      Montelukast) and the nude mouse xenograft model. Two drug administration regimens
      were established. The first regimen was established to investigate the importance
      of CysLT1R in tumor initiation. Nude mice were inoculated with 50 uM CysLT1R
      antagonist-pretreated HCT-116 colon cancer cells and received continued treatment
      (5 mg/kg/day, intraperitoneally). The second regimen aimed to address the role of
      CysLT1R in tumor progression. Nude mice were inoculated with non-pretreated HCT
      116 cells and did not receive CysLT1R antagonist treatment until recordable tumor
      appearance. Both regimens resulted in significantly reduced tumor size,
      attributed to changes in proliferation and apoptosis as determined by reduced Ki
      67 levels and increased levels of p21(WAF/Cip1) (P<0.01), cleaved caspase 3, and
      the caspase-cleaved product of cytokeratin 18. Decreased levels of VEGF (P<0.01)
      and reduced vessel size (P<0.05) were also observed, the latter only in the
      ZM198,615-pretreatment group. Furthermore, we performed a series of in vitro
      studies using the colon cancer cell line HCT-116 and CysLT1R antagonists. In
      addition to significant reductions in cell proliferation, adhesion and colony
      formation, we observed induction of cell cycle arrest and apoptosis in a dose
      dependent manner. The ability of Montelukast to inhibit growth of human colon
      cancer xenograft was further validated by using two additional colon cancer cell
      lines, SW-480 and HT-29. Our results demonstrate that CysLT1R antagonists inhibit
      growth of colon cancer xenografts primarily by reducing proliferation and
      inducing apoptosis of the tumor cells. 

PMID- 24039953
TI  - Characterization and prevention of the adsorption of surfactant protein D to
      polypropylene.
AB  - Surfactant Protein D (SP-D) is a multifunctional protein present in the lung and
      in respiratory secretions. In the process of developing new experimental
      approaches to examine SP-D function, we observed that SP-D adsorbs to
      polypropylene tubes to a great extent, thereby depleting SP-D from the solution.
      Although it is well known that proteins adsorb nonspecifically to plastic, this
      effect is usually diminished by treatments to make the plastic "low-retention" or
      "low-binding". However, these treatments actually increased the binding of SP-D
      to the plastic. In addition, this adsorption affected the results of several
      assays, including proteolytic cleavage assays. In order to block SP-D from
      adsorbing to polypropylene and the effects caused by this adsorption, we coated
      the tubes with bovine serum albumin (BSA), as is commonly performed for ELISAs.
      This coating greatly diminished the amount of SP-D sticking to the plastic,
      providing an inexpensive and effective method for preventing adsorption and the
      artifacts resulting from this adsorption. 

PMID- 24039954
TI  - New target genes of MITF-induced microRNA-211 contribute to melanoma cell
      invasion.
AB  - The non-coding microRNAs (miRNA) have tissue- and disease-specific expression
      patterns. They down-regulate target mRNAs, which likely impacts on most
      fundamental cellular processes. Differential expression patterns of miRNAs are
      currently being exploited for identification of biomarkers for early disease
      diagnosis, prediction of progression for melanoma and other cancers and as
      promising drug targets, since they can easily be inhibited or replaced in a given
      cellular context. Before successfully manipulating miRNAs in clinical settings,
      their precise expression levels, endogenous functions and thus their target genes
      have to be determined. MiR-211, a melanocyte lineage-specific small non-coding
      miRNA, is located in an intron of TRPM1, a target gene of the microphtalmia
      associated transcription factor (MITF). By transcriptionally up-regulating TRPM1,
      MITF, which is critical for both melanocyte differentiation and survival and for
      melanoma progression, indirectly drives the expression of miR-211. Expression of
      this miRNA is often reduced in melanoma samples. Here, we investigated functional
      roles of miR-211 by identifying and studying new target genes. We show that MITF
      correlated miR-211 expression levels are mostly but not always reduced in a panel
      of 11 melanoma cell lines and in primary and metastatic melanoma compared to
      normal melanocytes and nevi, respectively. MiR-211 itself only marginally
      impacted on cell invasion and migration, while perturbation of some new miR-211
      target genes, such as AP1S2, SOX11, IGFBP5, and SERINC3 significantly increased
      invasion. These results and the variable expression levels of miR-211 raise
      serious doubts on the value of miR-211 as a melanoma tumor-suppressing miRNA
      and/or as a biomarker for melanoma. 

PMID- 24039955
TI  - Ubiquitination-induced fluorescence complementation (UiFC) for detection of K48
      ubiquitin chains in vitro and in live cells.
AB  - Proteins can be modified with eight homogenous ubiquitin chains linked by an
      isopeptide bond between the C-terminus of one ubiquitin and an amine from one of
      the seven lysines or the N-terminal methionine of the next ubiquitin. These
      topologically distinct ubiquitin chains signal for many essential cellular
      functions, such as protein degradation, cell cycle progression, DNA repair, and
      signal transduction. The lysine 48 (K48)-linked ubiquitin chain is one of the
      most abundant chains and a major proteasome-targeting signal in cells. Despite
      recent advancements in imaging linkage-specific polyubiquitin chains, no tool is
      available for imaging K48 chains in live cells. Here we report on a
      ubiquitination-induced fluorescence complementation (UiFC) assay for detecting
      K48 ubiquitin chains in vitro and in live cells. For this assay, two
      nonfluorescent fragments of a fluorescent protein were fused to the ubiquitin
      interacting motifs (UIMs) of epsin1 protein. Upon simultaneous binding to a
      ubiquitin chain, the nonfluorescent fragments of the two fusion proteins are
      brought in close proximity to reconstitute fluorescence. When used in vitro, UiFC
      preferentially detected K48 ubiquitin chains with excellent signal-to-noise
      ratio. Time-lapse imaging revealed that UiFC is capable of monitoring increases
      in polyubiquitination induced by treatment with proteasome inhibitor, by agents
      that induce stress, and during mitophagy in live cells. 

PMID- 24039957
TI  - Stroke propensity is increased under atrial fibrillation hemodynamics: a
      simulation study.
AB  - Atrial fibrillation (AF) is the most common sustained dysfunction in heart rhythm
      clinically and has been identified as an independent risk factor for stroke
      through formation and embolization of thrombi. AF is associated with reduced
      cardiac output and short and irregular cardiac cycle length. Although the effect
      of AF on cardiac hemodynamic parameters has been reported, it remains unclear how
      the hemodynamic perturbations affect the potential embolization of blood clots to
      the brain that can cause stroke. To understand stroke propensity in AF, we
      performed computer simulations to describe trajectories of blood clots subject to
      the aortic flow conditions that represent normal heart rhythm and AF.
      Quantitative assessment of stroke propensity by blood clot embolism was carried
      out for a range of clot properties (e.g., 2-6 mm in diameter and 0-0.8 m/s
      ejection speed) under normal and AF flow conditions. The simulations demonstrate
      that the trajectory of clot is significantly affected by clot properties as well
      as hemodynamic waveforms which lead to significant variations in stroke
      propensity. The predicted maximum difference in stroke propensity in the left
      common carotid artery was shown to be about 60% between the normal and AF flow
      conditions examined. The results suggest that the reduced cardiac output and
      cycle length induced by AF can significantly increase the incidence of carotid
      embolism. The present simulations motivate further studies on patient-specific
      risk assessment of stroke in AF. 

PMID- 24039956
TI  - Delta(1)-pyrroline-5-carboxylate/glutamate biogenesis is required for fungal
      virulence and sporulation.
AB  - Proline dehydrogenase (Prodh) and Delta(1)-pyrroline-5-carboxylate dehydrogenase
      (P5Cdh) are two key enzymes in the cellular biogenesis of glutamate. Recombinant
      Prodh and P5Cdh proteins of the chestnut blight fungus Cryphonectria parasitica
      were investigated and showed activity in in vitro assays. Additionally, the C.
      parasitica Prodh and P5Cdh genes were able to complement the Saccharomyces
      cerevisiae put1 and put2 null mutants, respectively, to allow these proline
      auxotrophic yeast mutants to grow on media with proline as the sole source of
      nitrogen. Deletion of the Prodh gene in C. parasitica resulted in hypovirulence
      and a lower level of sporulation, whereas deletion of P5Cdh resulted in
      hypovirulence though no effect on sporulation; both Deltaprodh and Deltap5cdh
      mutants were unable to grow on minimal medium with proline as the sole nitrogen
      source. In a wild-type strain, the intracellular level of proline and the
      activity of Prodh and P5Cdh increased after supplementation of exogenous proline,
      though the intracellular Delta(1)-pyrroline-5-carboxylate (P5C) content remained
      unchanged. Prodh and P5Cdh were both transcriptionally down-regulated in cells
      infected with hypovirus. The disruption of other genes with products involved in
      the conversion of arginine to ornithine, ornithine and glutamate to P5C, and P5C
      to proline in the cytosol did not appear to affect virulence; however, asexual
      sporulation was reduced in the Deltapro1 and Deltapro2 mutants. Taken together,
      our results showed that Prodh, P5Cdh and related mitochondrial functions are
      essential for virulence and that proline/glutamate pathway components may
      represent down-stream targets of hypovirus regulation in C. parasitica. 

PMID- 24039958
TI  - Stochastic stabilization of phenotypic States: the genetic bistable switch as a
      case study.
AB  - We study by means of analytical calculation and stochastic simulations how
      intrinsic noise modifies the bifurcation diagram of gene regulatory processes
      that can be effectively described by the Langevin formalism. In a general
      context, our study raises the intriguing question of how biochemical fluctuations
      redesign the epigenetic landscape in differentiation processes. We have applied
      our findings to a general class of regulatory processes that includes the
      simplest case that displays a bistable behavior and hence phenotypic variability:
      the genetic auto-activating switch. Thus, we explain why and how the noise
      promotes the stability of the low-state phenotype of the switch and show that the
      bistable region is extended when increasing the intensity of the fluctuations.
      This phenomenology is found in a simple one-dimensional model of the genetic
      switch as well as in a more detailed model that takes into account the binding of
      the protein to the promoter region. Altogether, we prescribe the analytical means
      to understand and quantify the noise-induced modifications of the bifurcation
      points for a general class of regulatory processes where the genetic bistable
      switch is included. 

PMID- 24039959
TI  - Respiratory syncytial virus infection induces higher Toll-like receptor-3
      expression and TNF-alpha production than human metapneumovirus infection.
AB  - Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are common
      causes of respiratory infections in children. Diseases caused by hMPV are
      generally considered to be less severe than those caused by RSV; the underlying
      mechanisms, however, remain unknown. In the present study, the expressions of
      TLRs in airway epithelial cells and lungs of BALB/c mice infected by hMPV or RSV
      were measured in an attempt to explore the differences in the airway inflammation
      caused by the two viruses. Our results demonstrate that both hMPV and RSV
      infection upregulated the expressions of TLRs and inflammatory cytokines.
      Specifically, the TLR3 expression was revealed to be elevated in vitro and in
      mouse lungs. IFN-alpha produced by A549 cells after RSV or hMPV infection
      remained undistinguishable, whereas production of TNF-alpha was significantly
      higher after RSV infection than hMPV infection either in the presence or absence
      of Poly I:C. This study provides a clue that more severe clinical syndrome of RSV
      infection may be due to the greater magnitude of induction of airway inflammation
      by RSV involving TLR3 activation and production of TNF-alpha. 

PMID- 24039960
TI  - Structure-activity relationship of nerve-highlighting fluorophores.
AB  - Nerve damage is a major morbidity associated with numerous surgical
      interventions. Yet, nerve visualization continues to challenge even the most
      experienced surgeons. A nerve-specific fluorescent contrast agent, especially one
      with near-infrared (NIR) absorption and emission, would be of immediate benefit
      to patients and surgeons. Currently, there are only three classes of small
      molecule organic fluorophores that penetrate the blood nerve barrier and bind to
      nerve tissue when administered systemically. Of these three classes, the
      distyrylbenzenes (DSBs) are particularly attractive for further study. Although
      not presently in the NIR range, DSB fluorophores highlight all nerve tissue in
      mice, rats, and pigs after intravenous administration. The purpose of the current
      study was to define the pharmacophore responsible for nerve-specific uptake and
      retention, which would enable future molecules to be optimized for NIR optical
      properties. Structural analogs of the DSB class of small molecules were
      synthesized using combinatorial solid phase synthesis and commercially available
      building blocks, which yielded more than 200 unique DSB fluorophores. The nerve
      specific properties of all DSB analogs were quantified using an ex vivo nerve
      specific fluorescence assay on pig and human sciatic nerve. Results were used to
      perform quantitative structure-activity relationship (QSAR) modeling and to
      define the nerve-specific pharmacophore. All DSB analogs with positive ex vivo
      fluorescence were tested for in vivo nerve specificity in mice to assess the
      effect of biodistribution and clearance on nerve fluorescence signal. Two new DSB
      fluorophores with the highest nerve to muscle ratio were tested in pigs to
      confirm scalability. 

PMID- 24039961
TI  - Effects of bone marrow stromal cell transplantation through CSF on the subacute
      and chronic spinal cord injury in rats.
AB  - It has been demonstrated that the infusion of bone marrow stromal cells (BMSCs)
      through the cerebrospinal fluid (CSF) has beneficial effects on acute spinal cord
      injury (SCI) in rats. The present study examined whether BMSC infusion into the
      CSF is effective for subacute (1- and 2-week post-injury), and/or chronic (4-week
      post-injury) SCI in rats. The spinal cord was contused by dropping a weight at
      the thoracic 8-9 levels. BMSCs cultured from GFP-transgenic rats of the same
      strain were injected three times (once weekly) into the CSF through the fourth
      ventricle, beginning at 1, 2 and 4 weeks post-injury. At 4 weeks after initial
      injection, the average BBB score for locomotor assessment increased from 1.0-3.5
      points before injection to 9.0-10.9 points in the BMSC-injection subgroups,
      while, in the PBS (vehicle)-injection subgroups, it increased only from 0.5-4.0
      points before injection to 3.0-5.1 points. Numerous axons associated with Schwann
      cells extended longitudinally through the connective tissue matrices in the
      astrocyte-devoid lesion without being blocked at either the rostral or the caudal
      borders in the BMSC-injection subgroups. A small number of BMSCs were found to
      survive within the spinal cord lesion in SCI of the 1-week post-injury at 2 days
      of injection, but none at 7 days. No BMSCs were found in the spinal cord lesion
      at 2 days or at 7 days in the SCI of the 2-week and the 4-week post-injury
      groups. In an in vitro experiment, BMSC-injected CSF promoted the survival and
      the neurite extension of cultured neurons more effectively than did the PBS
      injected CSF. These results indicate that BMSCs had beneficial effects on
      locomotor improvement as well as on axonal regeneration in both subacute and
      chronic SCI rats, and the results also suggest that BMSCs might function as
      neurotrophic sources via the CSF. 

PMID- 24039962
TI  - Multivalent engagement of TFIID to nucleosomes.
AB  - The process of eukaryotic transcription initiation involves the assembly of basal
      transcription factor complexes on the gene promoter. The recruitment of TFIID is
      an early and important step in this process. Gene promoters contain distinct DNA
      sequence elements and are marked by the presence of post-translationally modified
      nucleosomes. The contributions of these individual features for TFIID recruitment
      remain to be elucidated. Here, we use immobilized reconstituted promoter
      nucleosomes, conventional biochemistry and quantitative mass spectrometry to
      investigate the influence of distinct histone modifications and functional DNA
      elements on the binding of TFIID. Our data reveal synergistic effects of H3K4me3,
      H3K14ac and a TATA box sequence on TFIID binding in vitro. Stoichiometry analyses
      of affinity purified human TFIID identified the presence of a stable dimeric
      core. Several peripheral TAFs, including those interacting with distinct promoter
      features, are substoichiometric yet present in substantial amounts. Finally, we
      find that the TAF3 subunit of TFIID binds to poised promoters in an H3K4me3
      dependent manner. Moreover, the PHD-finger of TAF3 is important for rapid
      induction of target genes. Thus, fine-tuning of TFIID engagement on promoters is
      driven by synergistic contacts with both DNA-elements and histone modifications,
      eventually resulting in a high affinity interaction and activation of
      transcription. 

PMID- 24039963
TI  - High preservation of CpG cytosine methylation patterns at imprinted gene loci in
      liver and brain of aged mice.
AB  - A gradual loss of the correct patterning of 5-methyl cytosine marks in gene
      promoter regions has been implicated in aging and age-related diseases, most
      notably cancer. While a number of studies have examined DNA methylation in aging,
      there is no consensus on the magnitude of the effects, particularly at imprinted
      loci. Imprinted genes are likely candidate to undergo age-related changes because
      of their demonstrated plasticity in utero, for example, in response to
      environmental cues. Here we quantitatively analyzed a total of 100 individual CpG
      sites in promoter regions of 11 imprinted and non-imprinted genes in liver and
      cerebral cortex of young and old mice using mass spectrometry. The results
      indicate a remarkably high preservation of methylation marks during the aging
      process in both organs. To test if increased genotoxic stress associated with
      premature aging would destabilize DNA methylation we analyzed two DNA repair
      defective mouse models showing a host of premature aging symptoms in liver and
      brain. However, also in these animals, at the end of their life span, we found a
      similarly high preservation of DNA methylation marks. We conclude that patterns
      of DNA methylation in gene promoters of imprinted genes are surprisingly stable
      over time in normal, postmitotic tissues and that the multiple documented changes
      with age are likely to involve exceptions to this pattern, possibly associated
      with specific cellular responses to age-related changes other than genotoxic
      stress. 

PMID- 24039964
TI  - Biocompatible coating of encapsulated cells using ionotropic gelation.
AB  - The technique of immunoisolated transplantation has seen in the last twenty years
      improvements in biocompatibility, long term stability and methods for avoidance
      of fibrosis in alginate capsules. However, two major problems are not yet solved:
      living cellular material that is not centered in the capsule is not properly
      protected from the hosts' immune system and the total transplant volume needs to
      be reduced. To solve these problems, we present a method for applying fully
      biocompatible alginate multilayers to a barium-alginate core without the use of
      polycations. We report on the factors that influence layer formation and
      stability and can therefore provide data for full adjustability of the additional
      layer. Although known for yeast and plant cells, this technique has not
      previously been demonstrated with mammalian cells or ultra-high viscous
      alginates. Viability of murine insulinoma cells was investigated by live-dead
      staining and live cell imaging, for murine Langerhans' islets viability and
      insulin secretion have been measured. No hampering effects of the second alginate
      layer were found. This multi-layer technique therefore has great potential for
      clinical and in vitro use and is likely to be central in alginate matrix based
      immunoisolated cell therapy. 

PMID- 24039965
TI  - Long-term valproate treatment increases brain neuropeptide Y expression and
      decreases seizure expression in a genetic rat model of absence epilepsy.
AB  - The mechanisms by which valproate, one of the most widely prescribed anti
      epileptic drugs, suppresses seizures have not been fully elucidated but may
      involve up-regulation of neuropeptide Y (NPY). We investigated the effects of
      valproate treatment in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) on
      brain NPY mRNA expression and seizure control. GAERS were administered either
      valproate (42 mg.kg(-1) hr(-1)) or saline continuously for 5 days.
      Electroencephalograms were recorded for 24 hrs on treatment days 1, 3 and 5 and
      the percentage of time spent in seizure activity was analysed. NPY mRNA
      expression was measured in different brain regions using qPCR. Valproate
      treatment suppressed seizures by 80% in GAERS (p<0.05) and increased NPY mRNA
      expression in the thalamus (p<0.05) compared to saline treatment. These results
      demonstrate that long-term valproate treatment results in an upregulation of
      thalamic expression of NPY implicating this as a potential contributor to the
      mechanism by which valproate suppresses absence seizures. 

PMID- 24039966
TI  - Identification and functional analysis of delta-9 desaturase, a key enzyme in
      PUFA Synthesis, isolated from the oleaginous diatom Fistulifera.
AB  - Oleaginous microalgae are one of the promising resource of nonedible biodiesel
      fuel (BDF) feed stock alternatives. Now a challenge task is the decrease of the
      long-chain polyunsaturated fatty acids (PUFAs) content affecting on the BDF
      oxidative stability by using gene manipulation techniques. However, only the
      limited knowledge has been available concerning the fatty acid and PUFA synthesis
      pathways in microalgae. Especially, the function of Delta9 desaturase, which is a
      key enzyme in PUFA synthesis pathway, has not been determined in diatom. In this
      study, 4 Delta(9) desaturase genes (fD9desA, fD9desB, fD9desC and fD9desD) from
      the oleaginous diatom Fistulifera were newly isolated and functionally
      characterized. The putative Delta(9) acyl-CoA desaturases in the endoplasmic
      reticulum (ER) showed 3 histidine clusters that are well-conserved motifs in the
      typical Delta(9) desaturase. Furthermore, the function of these Delta(9)
      desaturases was confirmed in the Saccharomyces cerevisiae ole1 gene deletion
      mutant (Deltaole1). All the putative Delta(9) acyl-CoA desaturases showed
      Delta(9) desaturation activity for C16?0 fatty acids; fD9desA and fD9desB also
      showed desaturation activity for C18?0 fatty acids. This study represents the
      first functional analysis of Delta(9) desaturases from oleaginous microalgae and
      from diatoms as the first enzyme to introduce a double bond in saturated fatty
      acids during PUFA synthesis. The findings will provide beneficial insights into
      applying metabolic engineering processes to suppressing PUFA synthesis in this
      oleaginous microalgal strain. 

PMID- 24039967
TI  - Searching in mother nature for anti-cancer activity: anti-proliferative and pro
      apoptotic effect elicited by green barley on leukemia/lymphoma cells.
AB  - Green barley extract (GB) was investigated for possible anti-cancer activity by
      examining its anti-proliferative and pro-apoptotic properties on human
      leukemia/lymphoma cell lines. Our results indicate that GB exhibits selective
      anti-proliferative activity on a panel of leukemia/lymphoma cells in comparison
      to non-cancerous cells. Specifically, GB disrupted the cell-cycle progression
      within BJAB cells, as manifested by G2/M phase arrest and DNA fragmentation, and
      induced apoptosis, as evidenced by phosphatidylserine (PS) translocation to the
      outer cytoplasmic membrane in two B-lineage leukemia/lymphoma cell lines. The pro
      apoptotic effect of GB was found to be independent of mitochondrial
      depolarization, thus implicating extrinsic cell death pathways to exert its
      cytotoxicity. Indeed, GB elicited an increase of TNF-alpha production, caspase-8
      and caspase-3 activation, and PARP-1 cleavage within pre-B acute lymphoblastic
      leukemia Nalm-6 cells. Moreover, caspase-8 and caspase-3 activation and PARP-1
      cleavage were strongly inhibited/blocked by the addition of the specific caspase
      inhibitors Z-VAD-FMK and Ac-DEVD-CHO. Furthermore, intracellular signaling
      analyses determined that GB treatment enhanced constitutive activation of Lck and
      Src tyrosine kinases in Nalm-6 cells. Taken together, these findings indicate
      that GB induced preferential anti-proliferative and pro-apoptotic signals within
      B-lineage leukemia/lymphoma cells, as determined by the following biochemical
      hallmarks of apoptosis: PS externalization, enhanced release of TNF-alpha,
      caspase-8 and caspase-3 activation, PARP-1 cleavage and DNA fragmentation Our
      observations reveal that GB has potential as an anti-leukemia/lymphoma agent
      alone or in combination with standard cancer therapies and thus warrants further
      evaluation in vivo to support these findings. 

PMID- 24039968
TI  - Association between the Catechol O-methyltransferase (COMT) Val158met
      polymorphism and different dimensions of impulsivity.
AB  - BACKGROUND: Impulsivity is a multidimensional construct which has been associated
      with dopaminergic neurotransmission. Nonetheless, until this moment, few studies
      addressed the relationship between different types of impulsivity and the single
      nucleotide polymorphism caused by a substitution of valine (val) with methionine
      (met) in the 158 codon of the Catechol-o-Methyltransferase gene (COMT-val158met).
      The present study aimed to investigate the association between val158met COMT
      polymorphism and impulsive behavior measured by two neuropsychological tests.
      METHODOLOGY/PRINCIPAL FINDINGS: We administered two neuropsychological tests, a
      Continuous Performance Task and the Iowa Gambling Task were applied to 195
      healthy participants to characterize their levels of motor, attentional and non
      planning impulsivity. Then, subjects were grouped by genotype, and their scores
      on impulsivity measures were compared. There were no significant differences
      between group scores on attentional and motor impulsivity. Those participants who
      were homozygous for the met allele performed worse in the Iowa Gambling Task than
      val/val and val/met subjects. CONCLUSIONS/SIGNIFICANCE: Our results suggest that
      met allele of val158met COMT polymorphism is associated with poor performance in
      decision-making/cognitive impulsivity task. The results reinforce the hypothesis
      that val and met alleles of the val158met polymorphism show functional
      dissociation and are related to different prefrontal processes.

PMID- 24039969
TI  - Translation of atherosclerotic plaque phase-contrast CT imaging from synchrotron
      radiation to a conventional lab-based X-ray source.
AB  - OBJECTIVES: Phase-contrast imaging is a novel X-ray based technique that provides
      enhanced soft tissue contrast. The aim of this study was to evaluate the
      feasibility of visualizing human carotid arteries by grating-based phase-contrast
      tomography (PC-CT) at two different experimental set-ups: (i) applying
      synchrotron radiation and (ii) using a conventional X-ray tube. MATERIALS AND
      METHODS: Five ex-vivo carotid artery specimens were examined with PC-CT either at
      the European Synchrotron Radiation Facility using a monochromatic X-ray beam (2
      specimens; 23 keV; pixel size 5.4 um), or at a laboratory set-up on a
      conventional X-ray tube (3 specimens; 35-40 kVp; 70 mA; pixel size 100 um).
      Tomographic images were reconstructed and compared to histopathology. Two
      independent readers determined vessel dimensions and one reader determined signal
      to-noise ratios (SNR) between PC-CT and absorption images. RESULTS: In total, 51
      sections were included in the analysis. Images from both set-ups provided
      sufficient contrast to differentiate individual vessel layers. All PCI-based
      measurements strongly predicted but significantly overestimated lumen, intima and
      vessel wall area for both the synchrotron and the laboratory-based measurements
      as compared with histology (all p<0.001 with slope >0.53 per mm(2), 95%-CI: 0.35
      to 0.70). Although synchrotron-based images were characterized by higher SNRs
      than laboratory-based images; both PC-CT set-ups had superior SNRs compared to
      corresponding conventional absorption-based images (p<0.001). Inter-reader
      reproducibility was excellent (ICCs >0.98 and >0.84 for synchrotron and for
      laboratory-based measurements; respectively). CONCLUSION: Experimental PC-CT of
      carotid specimens is feasible with both synchrotron and conventional X-ray
      sources, producing high-resolution images suitable for vessel characterization
      and atherosclerosis research.

PMID- 24039970
TI  - Identifying the genome-wide sequence variations and developing new molecular
      markers for genetics research by re-sequencing a Landrace cultivar of foxtail
      millet.
AB  - Foxtail millet (Setariaitalica) is a drought-resistant, barren-tolerant grain
      crop and forage. Currently, it has become a new model plant for cereal crops and
      biofuel grasses. Although two reference genome sequences were released recently,
      comparative genomics research on foxtail millet is still in its infancy. Using
      the Solexa sequencing technology, we performed genome re-sequencing on one
      important foxtail millet Landrace, Shi-Li-Xiang (SLX). Compared with the two
      reference genome sequences, the following genetic variation patterns were
      identified: 762,082 SNPs, 26,802 insertion/deletion polymorphisms of 1 to 5 bp in
      length (indels), and 10,109 structural variations (SVs) between SLX and Yugu1
      genomes; 915,434 SNPs, 28,546 indels and 12,968 SVs between SLX and Zhang gu
      genomes. Furthermore, based on the Yugu1 genome annotation, we found out that ~
      40% SNPs resided in genes containing NB-ARC domain, protein kinase or leucine
      rich repeats, which had higher non-synonymous to synonymous SNPs ratios than
      average, suggesting that the diversification of plant disease resistance proteins
      might be caused by pathogen pressure. In addition, out of the polymorphisms
      identified between SLX and Yugu1, 465 SNPs and 146 SVs were validated with more
      than 90% accuracy, which could be used as DNA markers for whole-genome genotyping
      and marker-assisted breeding. Here, we also represented an example of fine
      mapping and identifying a waxy locus in SLX using these newly developed DNA
      markers. This work provided important information that will allow a deeper
      understanding of the foxtail millet genome and will be helpful for dissecting the
      genetic basis of important traits in foxtail millet. 

PMID- 24039971
TI  - Evaluation of the patient acceptable symptom state (PASS) in Italian patients
      affected by systemic lupus erythematosus: association with disease activity
      indices.
AB  - OBJECTIVES: The aim of this study was to evaluate the discriminant capability of
      the patient acceptable symptom state (PASS) according to disease activity, in a
      cohort of Italian patients affected by systemic Lupus erythematosus (SLE).
      METHODS: Consecutive SLE patients were enrolled. At each visit, the patients
      underwent a complete physical examination and the clinical/laboratory data were
      collected in a standardized, computerized, and electronically-filled form. The
      evaluation of serum complement C3 and C4 levels and determination of
      autoantibodies was obtained. Disease activity was assessed with the SLEDAI-2K and
      ECLAM, while chronic damage was measured with the SLICC. Finally, PASS was
      assessed in all patients by asking to answer yes or no to a single question.
      RESULTS: One hundred sixty-five patients were enrolled (M/F 12/153; mean age
      40.4+/-11.8 years, mean disease duration 109.1+/-96.2 months). No patients
      refused to answer, suggesting the acceptability of PASS. A total of 80% of
      patients rated their state as acceptable. The patients with an acceptable status
      had significantly lower mean SLEDAI-2K and ECLAM scores than the others [1.8+/
      2.7 versus 3.4+/-2.3(P=0.004); 0.7+/-0.9 versus 1.4+/-1.1(P=0.0027)]. No
      significant differences were observed when considering chronic damage, evaluated
      with SLICC. CONCLUSIONS: In the clinical practice, SLE patients assessment
      performed by using complex disease activity indices such as SLEDAI-2K and ECLAM,
      could be time consuming. In our study, for the first time, we used PASS, a quick
      and easily comprehensible tool, to evaluate the patients' status, this single
      question seems to be able to discriminate patients with different disease
      activity, especially when this is determined by musculoskeletal involvement.

PMID- 24039972
TI  - Framingham risk score for prediction of cardiovascular diseases: a population
      based study from southern Europe.
AB  - BACKGROUND: The question about what risk function should be used in primary
      prevention remains unanswered. The Framingham Study proposed a new algorithm
      based on three key ideas: use of the four risk factors with the most weight
      (cholesterol, blood pressure, diabetes and smoking), prediction of overall
      cardiovascular diseases and incorporating the concept of vascular age. The
      objective of this study was to apply this new function in a cohort of the general
      non Anglo-Saxon population, with a 10-year follow-up to determine its validity.
      METHODS: The cohort was studied in 1992-94 and again in 2004-06. The sample
      comprised 959 randomly-selected persons, aged 30-74 years, who were
      representative of the population of Albacete, Spain. At the first examination
      cycle, needed data for the new function were collected and at the second
      examination, data on all events were recorded during the follow-up period.
      Discrimination was studied with ROC curves. Comparisons of prediction models and
      reality in tertiles (Hosmer-Lemeshow) were performed, and the individual survival
      functions were calculated. RESULTS: The mean risks for women and men,
      respectively, were 11.3% and 19.7% and the areas under the ROC curve were 0.789
      (95%CI, 0.716-0.863) and 0.780 (95%CI, 0.713-0.847) (P<0.001, both).
      Cardiovascular disease events occurred in the top risk tertiles. Of note were the
      negative predictive values in both sexes, and a good specificity in women (85.6%)
      and sensitivity in men (79.1%) when their risk for cardiovascular disease was
      high. This model overestimates the risk in older women and in middle-aged men.
      The cumulative probability of individual survival by tertiles was significant in
      both sexes (P<0.001). CONCLUSIONS: The results support the proposal for
      "reclassification" of Framingham. This study, with a few exceptions, passed the
      test of discrimination and calibration in a random sample of the general
      population from southern Europe.

PMID- 24039973
TI  - Environmental alkylphenols modulate cytokine expression in plasmacytoid dendritic
      cells.
AB  - BACKGROUND: Alkylphenols, such as nonylphenol (NP) and 4-octylphenol (4-OP), have
      the potential to disturb immune system due to their weak estrogen-like activity,
      an effect with potential serious public health impact due to the worldwide
      distribution of these substances. Plasmacytoid dendritic cells (PDCs) can secrete
      large amounts of type I IFNs and are critical in immune regulation. However,
      there has been limited study about the influence of alkylphenols on the function
      of pDCs. OBJECTIVE: The aim of this study was to examine the effect of
      alkylphenols on pDC functions in vitro and in vivo and then further explored the
      involved signaling pathways and epigenetic changes. METHODS: Circulating pDCs
      from human peripheral blood mononuclear cells were treated with alkylphenols with
      or without CpG stimulation. Alkylphenol-associated cytokine responses, signaling
      events, histone modifications and viral activity were further examined. In NP
      exposed mice, the effect of NP on splenic pDC function and allergic lung
      inflammation were also assessed. RESULTS: The results showed that NP increased
      the expression of TNF-alpha, but suppressed IL-10 production in the range of
      physiological doses, concomitant with activation of the MKK3/6-p38 signaling
      pathway and enhanced levels of acetylated histone 3 as well as histone 4 at the
      TNFA gene locus. Further, in CpG-stimulated pDCs, NP suppressed type I IFNs
      production, associated with down-regulation of IRF-7 and MKK1/2-ERK-Elk-1
      pathways and led to the impaired anti-enterovirus 71 activity in vitro.
      Additionally, splenic pDCs from NP-exposed mice showed similar cytokine changes
      upon CpG stimulation under conditions relevant to route and level of exposure in
      humans. NP treatment also enhanced allergic lung inflammation in vivo.
      CONCLUSION: Alkylphenols may influence pDCs' functions via their abilities to
      induce expression of a pro-inflammatory cytokine, TNF-alpha, and to suppress
      regulatory cytokines, including IL-10, IFN-alpha and IFN-beta, suggesting the
      potential impact of endocrine disrupting chemicals on immune regulation.

PMID- 24039974
TI  - Different land use intensities in grassland ecosystems drive ecology of microbial
      communities involved in nitrogen turnover in soil.
AB  - Understanding factors driving the ecology of N cycling microbial communities is
      of central importance for sustainable land use. In this study we report changes
      of abundance of denitrifiers, nitrifiers and nitrogen-fixing microorganisms
      (based on qPCR data for selected functional genes) in response to different land
      use intensity levels and the consequences for potential turnover rates. We
      investigated selected grassland sites being comparable with respect to soil type
      and climatic conditions, which have been continuously treated for many years as
      intensely used meadows (IM), intensely used mown pastures (IP) and extensively
      used pastures (EP), respectively. The obtained data were linked to above ground
      biodiversity pattern as well as water extractable fractions of nitrogen and
      carbon in soil. Shifts in land use intensity changed plant community composition
      from systems dominated by s-strategists in extensive managed grasslands to c
      strategist dominated communities in intensive managed grasslands. Along the
      different types of land use intensity, the availability of inorganic nitrogen
      regulated the abundance of bacterial and archaeal ammonia oxidizers. In contrast,
      the amount of dissolved organic nitrogen determined the abundance of denitrifiers
      (nirS and nirK). The high abundance of nifH carrying bacteria at intensive
      managed sites gave evidence that the amounts of substrates as energy source
      outcompete the high availability of inorganic nitrogen in these sites. Overall,
      we revealed that abundance and function of microorganisms involved in key
      processes of inorganic N cycling (nitrification, denitrification and N fixation)
      might be independently regulated by different abiotic and biotic factors in
      response to land use intensity. 

PMID- 24039976
TI  - Clonal variation in growth plasticity within a Bosmina longirostris population:
      the potential for resistance to toxic cyanobacteria.
AB  - Many aquatic organisms respond phenotypically, through morphological, behavioral,
      and physiological plasticity, to environmental changes. The small-size cladoceran
      Bosminalongirostris, a dominant zooplankter in eutrophic waters, displayed
      reduced growth rates in response to the presence of a toxic cyanobacterium,
      Microcystisaeruginosa, in their diets. The magnitude of growth reduction differed
      among 15 clones recently isolated from a single population. A significant
      interaction between clone and food type indicated a genetic basis for the
      difference in growth plasticity. The variation in phenotypic plasticity was
      visualized by plotting reaction norms with two diets. The resistance of each
      clone to dietary cyanobacteria was measured as the relative change in growth
      rates on the "poor" diet compared with the "good" diet. The enhanced resistance
      to M. aeruginosa in B. longirostris was derived from both the reduced slope of
      reaction norms and the increased mean growth rates with two diets. The large
      clonal variation within a B. longirostris population may contribute to local
      adaptation to toxic cyanobacteria and influence ecosystem function via clonal
      succession. 

PMID- 24039975
TI  - Differential regulation of Rab GTPase expression in monocyte-derived dendritic
      cells upon lipopolysaccharide activation: a correlation to maturation-dependent
      functional properties.
AB  - The regulation of Rab expression to modulate cellular function has recently been
      proposed. Dendritic cells are a prototypic example of cells that drastically
      alter their function in response to environmental cues by reducing endocytosis,
      secreting cytokines, changing surface protein repertoires and altering morphology
      and migration. This is not a binary event, but is subject to fluctuations through
      the activation process, termed maturation. Consequently, DCs transiently increase
      endocytosis and production of major histocompatibility complex class II
      molecules, and secrete inflammatory cytokines in infected tissues before
      migrating to secondary lymph nodes and releasing T cell polarizing factors. All
      these cellular processes rely on intracellular membrane transport, which is
      regulated by Rab family GTPases and their diverse effectors. Here we examine how
      the Rabs likely to be involved in these functions are regulated throughout DC
      maturation. We find that Rab expression is altered upon lipopolysaccharide
      induced activation, and discuss how this correlates to the reported functions of
      these cells during maturation. 

PMID- 24039977
TI  - Metabolic glucose status and pituitary pathology portend therapeutic outcomes in
      acromegaly.
AB  - INTRODUCTION: Acromegaly is frequently associated with impaired glucose tolerance
      and/or diabetes. To evaluate the relationship between glucose metabolism and
      acromegaly disease, we evaluated 269 consecutive patients from two referral
      centres. METHODS: Clinical presentation, pituitary tumor size and invasiveness,
      and pituitary pathology were captured in a dedicated database. RESULTS: 131 women
      and 138 men with a mean age of 53.8 years were included. Of these, 201 (74.7%)
      presented with a macroadenoma and 18 (6.7%) with a microadenoma. Radiographic
      invasion was present in 91 cases (33.8%). Mean tumor diameter was 1.86 cm (0.2
      4.6). Pituitary histopathologic findings revealed pure GH-producing somatotroph
      adenomas (SA) in 147 patients, prolactin-production by mixed lactotroph (LA) and
      SA or mammosomatotroph adenoma (MSA) in 46 [22.4%], acidophil stem cell adenoma
      in 6 [2.9%], and other diagnoses in 6 [2.9%]. Medical treatment included
      octreotide in 96 [36.9%] and in combination with pegvisomant or dopamine agonists
      in 63 [24.2%]. Nearly 80% of patients achieved IGF-1 normalization. Importantly,
      patients with pure somatotroph adenomas were significantly more likely to present
      with abnormal glucose metabolism [48.7%] than those with mixed adenomas [9.7%]
      [p<0.001] independent of GH/IGF-1 levels or tumor invasiveness. Abnormal glucose
      metabolism and pituitary pathology also remained linked following IGF-1
      normalization. Moreover patients with pure SA and abnormal glucose metabolism
      were significantly (p<0.001) less likely to achieve disease remission despite the
      same therapeutic strategies. Conversely, patients with mixed adenomas were more
      likely (OR: 2.766 (95% CI: 1.490-5.136) to achieve disease remission.
      CONCLUSIONS: Patients with pure somatotroph adenomas are more likely than those
      with mixed adenomas to exhibit abnormal glucose metabolism.

PMID- 24039978
TI  - Modelling landscape-level numerical responses of predators to prey: the case of
      cats and rabbits.
AB  - Predator-prey systems can extend over large geographical areas but empirical
      modelling of predator-prey dynamics has been largely limited to localised scales.
      This is due partly to difficulties in estimating predator and prey abundances
      over large areas. Collection of data at suitably large scales has been a major
      problem in previous studies of European rabbits (Oryctolagus cuniculus) and their
      predators. This applies in Western Europe, where conserving rabbits and predators
      such as Iberian lynx (Lynx pardinus) is important, and in other parts of the
      world where rabbits are an invasive species supporting populations of introduced,
      and sometimes native, predators. In pastoral regions of New Zealand, rabbits are
      the primary prey of feral cats (Felis catus) that threaten native fauna. We
      estimate the seasonal numerical response of cats to fluctuations in rabbit
      numbers in grassland-shrubland habitat across the Otago and Mackenzie regions of
      the South Island of New Zealand. We use spotlight counts over 1645 km of
      transects to estimate rabbit and cat abundances with a novel modelling approach
      that accounts simultaneously for environmental stochasticity, density dependence
      and varying detection probability. Our model suggests that cat abundance is
      related consistently to rabbit abundance in spring and summer, possibly through
      increased rabbit numbers improving the fecundity and juvenile survival of cats.
      Maintaining rabbits at low abundance should therefore suppress cat numbers,
      relieving predation pressure on native prey. Our approach provided estimates of
      the abundance of cats and rabbits over a large geographical area. This was made
      possible by repeated sampling within each season, which allows estimation of
      detection probabilities. A similar approach could be applied to predator-prey
      systems elsewhere, and could be adapted to any method of direct observation in
      which there is no double-counting of individuals. Reliable estimates of numerical
      responses are essential for managing both invasive and threatened predators and
      prey. 

PMID- 24039979
TI  - Geometry-driven cell organization determines tissue growths in scaffold pores:
      consequences for fibronectin organization.
AB  - To heal tissue defects, cells have to bridge gaps and generate new extracellular
      matrix (ECM). Macroporous scaffolds are frequently used to support the process of
      defect filling and thus foster tissue regeneration. Such biomaterials contain
      micro-voids (pores) that the cells fill with their own ECM over time. There is
      only limited knowledge on how pore geometry influences cell organization and
      matrix production, even though it is highly relevant for scaffold design. This
      study hypothesized that 1) a simple geometric description predicts cellular
      organization during pore filling at the cell level and that 2) pore closure
      results in a reorganization of ECM. Scaffolds with a broad distribution of pore
      sizes (macroporous starPEG-heparin cryogel) were used as a model system and
      seeded with primary fibroblasts. The strategies of cells to fill pores could be
      explained by a simple geometrical model considering cells as tensioned chords.
      The model matched qualitatively as well as quantitatively by means of cell number
      vs. open cross-sectional area for all pore sizes. The correlation between ECM
      location and cell position was higher when the pores were not filled with tissue
      (Pearson's coefficient rho = 0.45+/-0.01) and reduced once the pores were closed
      (rho = 0.26+/-0.04) indicating a reorganization of the cell/ECM network. Scaffold
      pore size directed the time required for pore closure and furthermore impacted
      the organization of the fibronectin matrix. Understanding how cells fill micro
      voids will help to design biomaterial scaffolds that support the endogenous
      healing process and thus allow a fast filling of tissue defects.

PMID- 24039980
TI  - Differential effect of actomyosin relaxation on the dynamic properties of focal
      adhesion proteins.
AB  - Treatment of cultured cells with inhibitors of actomyosin contractility induces
      rapid deterioration of stress fibers, and disassembly of the associated focal
      adhesions (FAs). In this study, we show that treatment with the Rho kinase
      inhibitor Y-27632, which blocks actomyosin contractility, induces disarray in the
      FA-associated actin bundles, followed by the differential dissociation of eight
      FA components from the adhesion sites. Live-cell microscopy indicated that the
      drug triggers rapid dissociation of VASP and zyxin from FAs (tau values of 7-8
      min), followed by talin, paxillin and ILK (tau ~16 min), and then by FAK,
      vinculin and kindlin-2 (tau = 25-28 min). Examination of the molecular kinetics
      of the various FA constituents, using Fluorescence Recovery After Photobleaching
      (FRAP), in the absence of or following short-term treatment with the drug,
      revealed major changes in the kon and koff values of the different proteins
      tested, which are in close agreement with their differential dissociation rates
      from the adhesion sites. These findings indicate that mechanical, actomyosin
      generated forces differentially regulate the molecular kinetics of individual FA
      associated molecules, and thereby modulate FA composition and stability. 

PMID- 24039981
TI  - Pregnancy in HIV clinical trials in Sub Saharan Africa: failure of consent or
      contraception?
AB  - OBJECTIVE: Higher than expected pregnancy rates have been observed in HIV related
      clinical trials in Sub-Saharan Africa. We designed a qualitative study to explore
      the factors contributing to high pregnancy rates among participants in two HIV
      clinical trials in Sub-Saharan Africa. METHODS: Female and male participants
      enrolled in one of two clinical HIV trials in south-west Uganda were approached.
      The trials were a phase III microbicide efficacy trial among HIV negative women
      using vaginal gel (MDP); and a trial of primary prevention prophylaxis for
      invasive cryptococcal disease using fluconazole among HIV infected men and women
      in Uganda (CRYPTOPRO). 14 focus group discussions and 8 in-depth interviews were
      conducted with HIV positive and negative women and their male partners over a six
      month period. Areas explored were their experiences about why and when one should
      get pregnant, factors affecting use of contraceptives, HIV status disclosure and
      trial product use. RESULTS: All respondents acknowledged being advised of the
      importance of avoiding pregnancy during the trial. Factors reported to contribute
      to pregnancy included; trust that the investigational product (oral
      capsules/vaginal gel) would not harm the baby, need for children, side effects
      that led to inconsistent contraceptive use, low acceptance of condom use among
      male partners. Attitudes towards getting pregnant are fluid within couples over
      time and the trials often last for more than a year. Researchers need to account
      for high pregnancy rates in their sample size calculations, and consider lesser
      used female initiated contraceptive options e.g. diaphragm or female condoms. In
      long clinical trials where there is a high fetal or maternal risk due to
      investigational product, researchers and ethics committees should consider a
      review of participants contraceptive needs/pregnancy desire review after a fixed
      period, as need for children, partners and health status of participants may
      alter over time.

PMID- 24039982
TI  - Glutathione status and the renal elimination of inorganic mercury in the Mrp2(-/
      ) mouse.
AB  - Multidrug resistance-associated proteins (MRP) 2 and 4 are localized in proximal
      tubular epithelial cells and participate in the renal elimination of xenobiotics.
      MRP2 has also been implicated in the renal and hepatic elimination of mercury.
      The current study tested the hypothesis that MRP2 and MRP4 are involved in renal
      and hepatic handling of inorganic mercury (Hg(2+)). We examined the disposition
      of Hg(2+) in Mrp2(-/-) mice and assessed the transport of mercuric conjugates in
      inside-out membrane vesicles containing human MRP4. Since MRP2 has been shown to
      utilize glutathione (GSH) for transport of select substrates, we examined renal
      concentrations of GSH and cysteine and the expression of glutamate cysteine
      ligase (GCL) in Mrp2(-/-) and FVB mice. The effect of Hg(2+) exposure on renal
      GSH levels was also assessed in these mice. Our data suggest that MRP2, but not
      MRP4, is involved in proximal tubular export of Hg(2+). In addition, GSH levels
      are greater in Mrp2(-/-) mice and exposure to Hg(2+) reduced renal levels of GSH.
      Expression of GCL was also altered in Mrp2(-/-) mice under normal conditions and
      following exposure to HgCl2. This study provides important novel data regarding
      the transport of Hg(2+) and the effect of Hg(2+) exposure on GSH levels. 

PMID- 24039983
TI  - Paraquat poisoning induces TNF-alpha-dependent iNOS/NO mediated
      hyporesponsiveness of the aorta to vasoconstrictors in rats.
AB  - Paraquat is a toxic herbicide that may induce acute lung injury, circulatory
      failure and death. The present work aimed at investigating whether there is
      systemic inflammation and vascular dysfunction after paraquat exposure and
      whether these parameters were related. There was neutrophilia and accumulation of
      neutrophils in lung and bronchoalveolar lavage of animals given paraquat. This
      was associated with an increase in serum levels of TNF-alpha. In rats given
      paraquat, the relaxant response of aortic rings to acetylcholine was not modified
      but the contractile response to phenylephrine was greatly reduced. Endothelium
      removal or treatment with non-selective (L-NAME) or selective (L-NIL) inhibitors
      of inducible nitric oxide synthase (iNOS) restored contraction of aortas. There
      was greater production of nitric oxide (NO), which was restored to basal level by
      L-NIL, and greater expression of iNOS in endothelial cells, as seen by Western
      blot analyses and confocal microscopy. Blockade of TNF-alpha reduced pulmonary
      and systemic inflammation and vascular dysfunction. Together, our results clearly
      show that paraquat causes pulmonary and systemic inflammation, and vascular
      dysfunction in rats. Vascular dysfunction is TNF-alpha dependent, associated with
      enhanced expression of iNOS in aortic endothelial cells and greater NO
      production, which accounts for the decreased responsiveness of aortas to
      vasoconstrictors. Blockers of TNF-alpha may be useful in patients with paraquat
      poisoning. 

PMID- 24039984
TI  - A novel splice-site mutation in the GJB2 gene causing mild postlingual hearing
      impairment.
AB  - The DFNB1 subtype of autosomal recessive, nonsyndromic hearing impairment, caused
      by mutations affecting the GJB2 (connexin-26) [corrected] gene, is highly
      prevalent in most populations worldwide. DFNB1 hearing impairment is mostly
      severe or profound and usually appears before the acquisition of speech
      (prelingual onset), though a small number of hypomorphic missense mutations
      result in mild or moderate deafness of postlingual onset. We identified a novel
      GJB2 splice-site mutation, c. -22-2A>C, in three siblings with mild postlingual
      hearing impairment that were compound heterozygous for c. -22-2A>C and c.35delG.
      Reverse transcriptase-PCR experiments performed on total RNA extracted from
      saliva samples from one of these siblings confirmed that c. -22-2A>C abolished
      the acceptor splice site of the single GJB2 intron, resulting in the absence of
      normally processed transcripts from this allele. However, we did isolate
      transcripts from the c. -22-2A>C allele that keep an intact GJB2 coding region
      and that were generated by use of an alternative acceptor splice site previously
      unknown. The residual expression of wild-type connexin-26 [corrected] encoded by
      these transcripts probably underlies the mild severity and late onset of the
      hearing impairment of these subjects.

PMID- 24039985
TI  - Did I pick the right colony? Pitfalls in the study of regulation of the phase
      variable antigen 43 adhesin.
AB  - Ag43 is an abundant outer membrane autotransporter adhesin present in most
      commensal and pathogenic Escherichia coli. Expression of the agn43 gene is
      characterized by a regulated reversible switch or phase variation between the
      agn43 ON and agn43 OFF states. Although the agn43 regulatory switch leads to a
      heterogeneous population of ON and OFF bacteria, studies of Ag43 seldom consider
      potential biases associated with phase variation. We monitored agn43 ON/OFF phase
      variation status genetically and phenotypically and we show that the use of
      populations with random agn43 ON or OFF status could result in misleading
      conclusions about Ag43 function or regulation. In particular, we demonstrate that
      Lrp and MqsR, previously identified as agn43 regulators, do not regulate agn43
      expression or ON/OFF switch frequency. We also show that biofilm formation in
      dynamic flow conditions does not influence agn43 ON/OFF switching but physically
      selects aggregating agn43 ON cells. This indicates that misinterpretation is
      possible when studying gene expression within biofilms. Finally, we provide
      evidence that ignoring the initial agn43 ON/OFF status of the E. coli populations
      studied is likely to bias analyses of phenotypes associated with other E. coli
      adhesins. This study therefore emphasizes the importance of monitoring Ag43 phase
      variation and indicates that caution is required when interpreting experiments
      using strains that are neither deleted for agn43 nor carefully assessed for agn43
      ON/OFF status. 

PMID- 24039986
TI  - Influence of sub-surface irrigation on soil conditions and water irrigation
      efficiency in a cherry orchard in a hilly semi-arid area of northern China.
AB  - Sub-surface irrigation (SUI) is a new water-saving irrigation technology. To
      explore the influence of SUI on soil conditions in a cherry orchard and its water
      saving efficiency, experiments were conducted from 2009 to 2010 using both SUI
      and flood irrigation (FLI) and different SUI quotas in hilly semi-arid area of
      northern China. The results demonstrated the following: 1) The bulk density of
      the soil under SUI was 6.8% lower than that of soil under FLI (P<0.01). The total
      soil porosity, capillary porosity and non-capillary porosity of soils using SUI
      were 11.7% (P<0.01), 8.7% (P<0.01) and 43.8% (P<0.01) higher than for soils using
      FLI. 2) The average soil temperatures at 0, 5, 10, 15 and 20 cm of soil depth
      using SUI were 1.7, 1.1, 0.7, 0.4 and 0.3 degrees C higher than those for FLI,
      specifically, the differences between the surface soil layers were more
      significant. 3) Compared with FLI, the average water-saving efficiency of SUI was
      55.6%, and SUI increased the irrigation productivity by 7.9-12.3 kg m(-3) ha(-1).
      4) The soil moisture of different soil layers using SUI increased with increases
      in the irrigation quotas, and the soil moisture contents under SUI were
      significantly higher in the 0-20 cm layer and in the 21-50 cm layer than those
      under FLI (P<0.01). 5) The average yields of cherries under SUI with irrigation
      quotas of 80-320 m(3) ha(-1) were 8.7%-34.9% higher than those in soil with no
      irrigation (CK2). The average yields of cherries from soils using SUI were 4.5%
      12.2% higher than using FLI. It is appropriate to irrigate 2-3 times with 230
      m(3) ha(-1) per application using SUI in a year with normal rainfall. Our
      findings indicated that SUI could maintain the physical properties, greatly
      improve irrigation water use efficiency, and significantly increase fruit yields
      in hilly semi-arid areas of northern China. 

PMID- 24039987
TI  - Behavioral disinhibition and sexual risk behavior among adolescents and young
      adults in Malawi.
AB  - BACKGROUND: While behavioral factors such as early age of sexual debut,
      inconsistent use of condoms and multiple sexual partners have been studied in
      Africa, less is known about how characteristics such as impulsivity and
      externalizing behaviors relate to HIV-related sexual risk-taking in that region.
      The purpose of this study was to develop a culturally adapted behavioral
      disinhibition index in a sample of adolescents and young adults in Malawi. We
      then sought to examine the relationship between the index and sexual risk
      behavior as measured by multiple sexual partners and number of lifetime sexual
      partners. METHODS: Cross-sectional data were collected from 2342 participants in
      rural Malawi aged 15 to 29 years. We constructed a disinhibitory behavior score
      (DBS) using questions assessing disinhibitory behaviors. Bivariate analyses were
      conducted to assess the relationships among the individual DBS component
      behaviors. We utilized multivariable logistic regression to determine the
      association of the DBS with multiple sexual partners, and negative binomial
      regression to model the relationship between the DBS and number of lifetime
      sexual partners. FINDINGS: Nearly all the DBS component behaviors were
      significantly associated in the bivariate analyses. The DBS was associated with
      having multiple sexual partners (OR 1.97; 95% CI 1.57-2.48) in the multivariable
      logistic regression analysis. Further, negative binomial regression results
      demonstrated that the DBS was associated with an increased number of lifetime
      sexual partners (OR 1.11; 95% CI 1.07-1.16). CONCLUSIONS: HIV preventive programs
      in Africa should take into consideration disinhibitory behaviors that may be
      associated with sexual risk-taking. The DBS can be used as a simple tool to
      identify those who may be more likely to engage in these behaviors and provide
      useful information regarding which groups of individuals particularly need to be
      targeted for behavior change interventions.

PMID- 24039988
TI  - A novel alpha-L-arabinofuranosidase of family 43 glycoside hydrolase (Ct43Araf)
      from Clostridium thermocellum.
AB  - The study describes a comparative analysis of biochemical, structural and
      functional properties of two recombinant derivatives from Clostridium
      thermocellum ATCC 27405 belonging to family 43 glycoside hydrolase. The family 43
      glycoside hydrolase encoding alpha-L-arabinofuranosidase (Ct43Araf) displayed an
      N-terminal catalytic module CtGH43 (903 bp) followed by two carbohydrate binding
      modules CtCBM6A (405 bp) and CtCBM6B (402 bp) towards the C-terminal. Ct43Araf
      and its truncated derivative CtGH43 were cloned in pET-vectors, expressed in
      Escherichia coli and functionally characterized. The recombinant proteins
      displayed molecular sizes of 63 kDa (Ct43Araf) and 34 kDa (CtGH43) on SDS-PAGE
      analysis. Ct43Araf and CtGH43 showed optimal enzyme activities at pH 5.7 and 5.4
      and the optimal temperature for both was 50 degrees C. Ct43Araf and CtGH43 showed
      maximum activity with rye arabinoxylan 4.7 Umg(-1) and 5.0 Umg(-1), respectively,
      which increased by more than 2-fold in presence of Ca(2+) and Mg(2+) salts. This
      indicated that the presence of CBMs (CtCBM6A and CtCBM6B) did not have any effect
      on the enzyme activity. The thin layer chromatography and high pressure anion
      exchange chromatography analysis of Ct43Araf hydrolysed arabinoxylans (rye and
      wheat) and oat spelt xylan confirmed the release of L-arabinose. This is the
      first report of alpha-L-arabinofuranosidase from C. thermocellum having the
      capacity to degrade both p-nitrophenol-alpha-L-arabinofuranoside and p
      nitrophenol-alpha-L-arabinopyranoside. The protein melting curves of Ct43Araf and
      CtGH43 demonstrated that CtGH43 and CBMs melt independently. The presence of
      Ca(2+) ions imparted thermal stability to both the enzymes. The circular
      dichroism analysis of CtGH43 showed 48% beta-sheets, 49% random coils but only 3%
      alpha-helices. 

PMID- 24039989
TI  - A survey of the perceived risk for stroke among community residents in western
      urban China.
AB  - BACKGROUND AND PURPOSE: Persons who perceive their risk for stroke can promote
      the intervention of stroke risk factors and reduce the risk of stroke occurrence.
      Our purpose was to assess the knowledge of stroke risk factors and the level of
      perceived risk for stroke. METHODS: In 2011, a population-based face-to-face
      interview survey was conducted in Yuzhong district, Chongqing. A total of 1500
      potential participants aged >=18 years old were selected using a multi-stage
      sampling method. The knowledge of stroke risk factors and perceived risk for
      stroke was surveyed. RESULTS: A total of 941 participants completed the
      questionnaire survey. The respondents' awareness rate of stroke risk factors
      ranged between 53.3% and 87.2%. The community residents' perceived risk for
      stroke was only 17.7%. Multiple logistic regression analysis showed that 45-64
      years age group, a history of hypertension, hyperlipidemia, heart disease, and
      stroke were independent predictors of perceived risk for stroke. Perceived risk
      for stroke increased as the number of risk factors increased (P<0.001). However,
      even for respondents with three or more risk factors, only 41% perceived
      themselves to be at risk for stroke. CONCLUSIONS: In this population-based
      survey, few community residents perceived risk for stroke, even among those with
      multiple stroke risk factors, most did not perceive themselves to be at risk for
      stroke. Persons with 45-64 years old, a history of hypertension, hyperlipidemia,
      heart disease or stroke were more likely to perceive risk for stroke. The
      awareness of the risk for stroke has yet to be enhanced among community
      residents.

PMID- 24039990
TI  - A toolbox for tuberculosis (TB) diagnosis: an Indian multicentric study (2006
      2008). Evaluation of QuantiFERON-TB gold in tube for TB diagnosis.
AB  - BACKGROUND: The aim of this multicentric prospective study in India was to assess
      the performance of the QuantiFERON TB-Gold in tube (QFT-GIT), Tuberculin Skin
      Test (TST) and microbiological results as additional tools for diagnosing active
      tuberculosis (TB) and latent infection (LTBI) according to Human Immunodeficiency
      Virus (HIV) status. METHODS: Individuals with and without active TB and HIV
      infection were enrolled between 2006-2008. QFT-GIT and TST results were analyzed
      per se and in combination with microbiological data. RESULTS: Among the 276
      individuals (96 active pulmonary TB and 180 no active TB) tested by QFT-GIT, 18
      indeterminate results (6.5%) were found, more significantly numerous in the HIV
      infected (15/92; 16.3%) than the HIV-uninfected (3/184; 1.6%)(p<0.0001). QFT-GIT
      sensitivity for active TB was 82.3% and 92.9% respectively after including or
      excluding indeterminate results. Clinical sensitivity was significantly lower in
      the HIV-infected (68.4%) than the HIV-uninfected (91.4%) patients (p = 0.0059).
      LTBI was detected in 49.3% of subjects without active TB but varied according to
      TB exposure. When the TST and QFT-GIT were concomitantly performed, the
      respective sensitivity for active TB diagnosis was 95.0% and 85.0% in the HIV
      uninfected (p = 0.60), and 66.7% and 51.5% in the HIV-infected patients (p =
      0.32). QFT-GIT and TST respective specificity for active TB in the HIV-uninfected
      was 25.0% and 57.1% (p = 0.028), and 64.8% and 83.3% in the HIV-infected (p =
      0.047). In those with active TB, QFT-GIT results were not associated with
      microbiological parameters (smear grade, liquid culture status, time-to
      positivity of culture) or clinical suspicion of active TB score (provided by the
      clinicians at enrollment). Combining microbiological tests with both
      immunological tests significantly increased sensitivity for active TB diagnosis
      (p = 0.0002), especially in the HIV-infected individuals (p = 0.0016).
      CONCLUSION: QFT-GIT and TST have similar diagnostic value for active TB
      diagnosis. In HIV-infected patients, combining microbiological tests with both
      immunological tests significantly increases the sensitivity for active TB
      diagnosis.

PMID- 24039991
TI  - In silico mechanistic profiling to probe small molecule binding to
      sulfotransferases.
AB  - Drug metabolizing enzymes play a key role in the metabolism, elimination and
      detoxification of xenobiotics, drugs and endogenous molecules. While their
      principal role is to detoxify organisms by modifying compounds, such as
      pollutants or drugs, for a rapid excretion, in some cases they render their
      substrates more toxic thereby inducing severe side effects and adverse drug
      reactions, or their inhibition can lead to drug-drug interactions. We focus on
      sulfotransferases (SULTs), a family of phase II metabolizing enzymes, acting on a
      large number of drugs and hormones and showing important structural flexibility.
      Here we report a novel in silico structure-based approach to probe ligand binding
      to SULTs. We explored the flexibility of SULTs by molecular dynamics (MD)
      simulations in order to identify the most suitable multiple receptor
      conformations for ligand binding prediction. Then, we employed structure-based
      docking-scoring approach to predict ligand binding and finally we combined the
      predicted interaction energies by using a QSAR methodology. The results showed
      that our protocol successfully prioritizes potent binders for the studied here
      SULT1 isoforms, and give new insights on specific molecular mechanisms for
      diverse ligands' binding related to their binding sites plasticity. Our best QSAR
      models, introducing predicted protein-ligand interaction energy by using docking,
      showed accuracy of 67.28%, 78.00% and 75.46%, for the isoforms SULT1A1, SULT1A3
      and SULT1E1, respectively. To the best of our knowledge our protocol is the first
      in silico structure-based approach consisting of a protein-ligand interaction
      analysis at atomic level that considers both ligand and enzyme flexibility, along
      with a QSAR approach, to identify small molecules that can interact with II phase
      dug metabolizing enzymes. 

PMID- 24039992
TI  - Importance of gene duplication in the evolution of genomic imprinting revealed by
      molecular evolutionary analysis of the type I MADS-box gene family in Arabidopsis
      species.
AB  - The pattern of molecular evolution of imprinted genes is controversial and the
      entire picture is still to be unveiled. Recently, a relationship between the
      formation of imprinted genes and gene duplication was reported in genome-wide
      survey of imprinted genes in Arabidopsis thaliana. Because gene duplications
      influence the molecular evolution of the duplicated gene family, it is necessary
      to investigate both the pattern of molecular evolution and the possible
      relationship between gene duplication and genomic imprinting for a better
      understanding of evolutionary aspects of imprinted genes. In this study, we
      investigated the evolutionary changes of type I MADS-box genes that include
      imprinted genes by using relative species of Arabidopsis thaliana (two subspecies
      of A. lyrata and three subspecies of A. halleri). A duplicated gene family
      enables us to compare DNA sequences between imprinted genes and its homologs. We
      found an increased number of gene duplications within species in clades
      containing the imprinted genes, further supporting the hypothesis that local gene
      duplication is one of the driving forces for the formation of imprinted genes.
      Moreover, data obtained by phylogenetic analysis suggested "rapid evolution" of
      not only imprinted genes but also its closely related orthologous genes, which
      implies the effect of gene duplication on molecular evolution of imprinted genes.

PMID- 24039993
TI  - Keratin23 (KRT23) knockdown decreases proliferation and affects the DNA damage
      response of colon cancer cells.
AB  - Keratin 23 (KRT23) is strongly expressed in colon adenocarcinomas but absent in
      normal colon mucosa. Array based methylation profiling of 40 colon samples showed
      that the promoter of KRT23 was methylated in normal colon mucosa, while
      hypomethylated in most adenocarcinomas. Promoter methylation correlated with
      absent expression, while increased KRT23 expression in tumor samples correlated
      with promoter hypomethylation, as confirmed by bisulfite sequencing.
      Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA
      mediated stable KRT23 knockdown in colon cancer cell lines showed that KRT23
      depletion affected molecules of the cell cycle and DNA replication, recombination
      and repair. In vitro analyses confirmed that KRT23 depletion significantly
      decreased the cellular proliferation of SW948 and LS1034 cells and markedly
      decreased the expression of genes involved in DNA damage response, mainly
      molecules of the double strand break repair homologous recombination pathway.
      KRT23 knockdown decreased the transcript and protein expression of key molecules
      as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer
      cells more sensitive to irradiation and reduced proliferation of the KRT23
      depleted cells compared to irradiated control cells. 

PMID- 24039994
TI  - Terpenoid variations within and among half-sibling avocado trees, Persea
      americana Mill. (Lauraceae).
AB  - Chemical analyses were conducted to determine the qualitative and quantitative
      differences in monoterpenes and sesquiterpenes in plant material from avocado
      trees, Persea americana Mill. (Lauraceae). The initial study analyzed plant
      material sampled from the trunk to the leaves through different branch diameters
      to quantify proximo-distal spatial differences within a tree. All trees were
      seedlings initiated from a single maternal tree. Two-way analysis of variance was
      conducted on 34 chemicals that comprised at least 3% of the total chemical
      content of at least one tree and/or location within a tree. There were
      significant interactions between genotype and location sampled for most
      chemicals. Parentage analysis using microsatellite molecular markers (SSR's)
      determined that the four trees had three fathers and that they represented two
      full-siblings and two half-sibling trees. Descriptive discriminant analysis found
      that both genotype and location within a tree could be separated based on
      chemical content, and that the chemical content from full-siblings tended to be
      more similar than chemical content from half-siblings. To further explore the
      relationship between genetic background and chemical content, samples were
      analyzed from leaf material from 20 trees that included two sets of full-sibling
      seedling trees, the maternal tree and the surviving paternal tree. Descriptive
      discriminant analysis found good separation between the two full-sibling groups,
      and that the separation was associated with chemistry of the parental trees. Six
      groups of chemicals were identified that explained the variation among the trees.
      We discuss the results in relation to the discrimination process used by wood
      boring insects for site-selection on host trees, for tree selection among
      potential host trees, and the potential use of terpenoid chemical content in
      chemotaxonomy of avocado trees. 

PMID- 24039995
TI  - miR-140 suppresses tumor growth and metastasis of non-small cell lung cancer by
      targeting insulin-like growth factor 1 receptor.
AB  - MicroRNAs (miRNAs) are a class of small noncoding RNA molecules that play
      important roles in carcinogenesis and tumor progression. In this study, we
      investigated the roles and mechanisms of miR-140 in human non-small cell lung
      cancer (NSCLC). We found that miR-140 is significantly downregulated in NSCLC
      tissues and cell lines. Both gain-of-function and loss-of-function studies
      demonstrated that miR-140 suppresses NSCLC cell proliferation, migration, and
      invasion in vitro. Importantly, overexpression of miR-140 effectively repressed
      tumor growth and metastasis in nude mouse models. Integrated analysis identified
      IGF1R as a direct and functional target of miR-140. Knockdown of IGF1R inhibited
      cell proliferation and invasion resembling that of miR-140 overexpression, while
      overexpression of IGF1R attenuated the function of miR-140 in NSCLC cells.
      Together, our results highlight the significance of miR-140 and IGF1R in the
      development and progression of NSCLC. 

PMID- 24039996
TI  - Asymmetries of influence: differential effects of body postures on perceptions of
      emotional facial expressions.
AB  - The accuracy and speed with which emotional facial expressions are identified is
      influenced by body postures. Two influential models predict that these congruency
      effects will be largest when the emotion displayed in the face is similar to that
      displayed in the body: the emotional seed model and the dimensional model. These
      models differ in whether similarity is based on physical characteristics or
      underlying dimensions of valence and arousal. Using a 3-alternative forced-choice
      task in which stimuli were presented briefly (Exp 1a) or for an unlimited time
      (Exp 1b) we provide evidence that congruency effects are more complex than either
      model predicts; the effects are asymmetrical and cannot be accounted for by
      similarity alone. Fearful postures are especially influential when paired with
      facial expressions, but not when presented in a flanker task (Exp 2). We suggest
      refinements to each model that may account for our results and suggest that
      additional studies be conducted prior to drawing strong theoretical conclusions. 

PMID- 24039997
TI  - Gene targeting in the red alga Cyanidioschyzon merolae: single- and multi-copy
      insertion using authentic and chimeric selection markers.
AB  - The unicellular red alga Cyanidioschyzon merolae is an emerging model organism
      for studying organelle division and inheritance: the cell is composed of an
      extremely simple set of organelles (one nucleus, one mitochondrion and one
      chloroplast), and their genomes are completely sequenced. Although a fruitful set
      of cytological and biochemical methods have now been developed, gene targeting
      techniques remain to be fully established in this organism. Thus far, only a
      single selection marker, URA Cm-Gs , has been available that complements the
      uracil-auxotrophic mutant M4. URA Cm-Gs , a chimeric URA5.3 gene of C. merolae
      and the related alga Galdieria sulphuraria, was originally designed to avoid gene
      conversion of the mutated URA5.3 allele in the parental strain M4. Although an
      early example of targeted gene disruption by homologous recombination was
      reported using this marker, the genome structure of the resultant transformants
      had never been fully characterized. In the current study, we showed that the use
      of the chimeric URA Cm-Gs selection marker caused multicopy insertion at high
      frequencies, accompanied by undesired recombination events at the targeted loci.
      The copy number of the inserted fragments was variable among the transformants,
      resulting in high yet uneven levels of transgene expression. In striking
      contrast, when the authentic URA5.3 gene (URA Cm-Cm ) was used as a selection
      marker, efficient single-copy insertion was observed at the targeted locus. Thus,
      we have successfully established a highly reliable and reproducible method for
      gene targeting in C. merolae. Our method will be applicable to a number of
      genetic manipulations in this organism, including targeted gene disruption,
      replacement and tagging.

PMID- 24039998
TI  - Secreted and transmembrane 1A is a novel co-stimulatory ligand.
AB  - Most T cell responses to pathogens or self antigens are modulated through the
      action of regulatory T cells and tissue-specific inhibitory mechanisms. To this
      end, several receptor-ligand pairs have evolved which either augment or diminish
      T cell function. Here we describe the tissue ligand SECTM1A (Secreted and
      transmembrane1A) as an alternative murine CD7 ligand. We show that SECTM1A, like
      SECTM1B, binds strongly to CD7, and that SECTM1B was able to compete with SECTM1A
      for CD7 binding. SECTM1A is ubiquitously expressed and has two major alternative
      transcripts which differ in expression between tissues. Both immobilised soluble
      forms of SECTM1A and SECTM1B and cell surface anchored forms demonstrated
      opposing effects on CD4+ T cell activation. Whereas SECTM1A acted as a co
      stimulator of T cells, enhancing IL-2 production and proliferation, SECTM1B
      proved inhibitory to TCR mediated T cell activation. Surprisingly, both
      functional outcomes proved to be CD7-independent, indicating the existence of
      alternative receptors for both ligands. We used a SECTM1A-Fc fusion protein to
      immunoprecipitate potential alternative ligands from detergent lysates of CD7(-/
      ) T cells and, using mass spectrometry, identified GITR as a SECTM1A binder.
      SECTM1A was found to bind to activated CD4+ and CD8+ T cells as well as to CHO
      cells expressing cell surface GITR. Binding of SECTM1A to activated primary T
      cells was inhibited by either GITRL-Fc or anti GITR antibodies. Thus SECTM1A and
      SECTM1B represent novel reciprocal alternative ligands which may function to
      modulate the activation of effector and regulatory T cells. The ability of
      SECTM1A to activate T cells may be explained by its ability to bind to GITR. 

PMID- 24039999
TI  - Association between 5p12 genomic markers and breast cancer susceptibility:
      evidence from 19 case-control studies.
AB  - BACKGROUND: The association between polymorphisms on 5p12 and breast cancer (BC)
      has been widely evaluated since it was first identified through genome-wide
      association approach; however, the studies have yielded contradictory results. We
      sought to investigate this inconsistency by performing a comprehensive meta
      analysis on two wildly studied polymorphisms (rs10941679 and rs4415084) on 5p12.
      METHODS: Databases including Pubmed, EMBASE, Web of Science, EBSCO, and Cochrane
      Library databases were searched to find relevant studies. Odds ratios (ORs) with
      95% confidence intervals (CIs) were used to assess the strength of association.
      The random-effects model was applied, addressing heterogeneity and publication
      bias. RESULTS: A total of 19 articles involving 100,083 cases and 163,894
      controls were included. An overall random-effects per-allele OR of 1.09 (95% CI:
      1.06-1.12; P = 4.5 * 10(-8)) and 1.09 (95% CI: 1.05-1.12; P = 4.2 * 10(-7)) was
      found for the rs10941679 and rs4415084 polymorphism respectively. Significant
      results were found in Asians and Caucasians when stratified by ethnicity; whereas
      no significant associations were found among Africans/African-Americans. Similar
      results were also observed using dominant or recessive genetic models. In
      addition, we find both rs4415084 and rs10941679 conferred significantly greater
      risks of ER-positive breast cancer than of ER-negative tumors. CONCLUSIONS: Our
      findings demonstrated that rs10941679-G allele and rs4415084-T allele might be
      risk-conferring factors for the development of breast cancer, especially in
      Caucasians and East-Asians.

PMID- 24040000
TI  - Brain white matter shape changes in amyotrophic lateral sclerosis (ALS): a
      fractal dimension study.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative
      disorder. Current diagnosis time is about 12-months due to lack of objective
      methods. Previous brain white matter voxel based morphometry (VBM) studies in ALS
      reported inconsistent results. Fractal dimension (FD) has successfully been used
      to quantify brain WM shape complexity in various neurological disorders and
      aging, but not yet studied in ALS. Therefore, we investigated WM morphometric
      changes using FD analyses in ALS patients with different clinical phenotypes. We
      hypothesized that FD would better capture clinical features of the WM morphometry
      in different ALS phenotypes than VBM analysis. High resolution MRI T1-weighted
      images were acquired in controls (n = 11), and ALS patients (n = 89). ALS
      patients were assigned into four subgroups based on their clinical phenotypes.VBM
      analysis was carried out using SPM8. FD values were estimated for brain WM
      skeleton, surface and general structure in both controls and ALS patients using
      our previously published algorithm. No significant VBM WM changes were observed
      between controls and ALS patients and among the ALS subgroups. In contrast,
      significant (p<0.05) FD reductions in skeleton and general structure were
      observed between ALS with dementia and other ALS subgroups. No significant
      differences in any of the FD measures were observed between control and ALS
      patients. FD correlated significantly with revised ALS functional rating scale
      (ALSFRS-R) score a clinical measure of function. Results suggest that brain WM
      shape complexity is more sensitive to ALS disease process when compared to
      volumetric VBM analysis and FD changes are dependent on the ALS phenotype.
      Correlation between FD and clinical measures suggests that FD could potentially
      serve as a biomarker of ALS pathophysiology, especially after confirmation by
      longitudinal studies.

PMID- 24040001
TI  - Differential expression of IL-17, 22 and 23 in the progression of colorectal
      cancer in patients with K-ras mutation: Ras signal inhibition and crosstalk with
      GM-CSF and IFN-gamma.
AB  - Recent studies have suggested that aberrant K-ras signaling is responsible for
      triggering immunological responses and inflammation-driven tumorigenesis.
      Interleukins IL-17, IL-22, and IL-23 have been reported in various types of
      malignancies, but the exact mechanistic role of these molecules remains to be
      elucidated. Given the role of K-ras and the involvement of interleukins in
      colorectal tumorigenesis, research efforts are reported for the first time,
      showing that differentially expressed interleukin IL-17, IL-22, and IL-23 levels
      are associated with K-ras in a stage-specific fashion along colorectal cancer
      progression. Specifically, a) the effect of K-ras signaling was investigated in
      the overall expression of interleukins in patients with colorectal cancer and
      healthy controls, and b) an association was established between mutant K-ras and
      cytokines GM-CSF and IFN-gamma. The results indicate that specific interleukins
      are differentially expressed in K-ras positive patients and the use of K-ras
      inhibitor Manumycin A decreases both interleukin levels and apoptosis in Caco-2
      cells by inhibiting cell viability. Finally, inflammation-driven GM-CSF and IFN
      gamma levels are modulated through interleukin expression in tumor patients, with
      interleukin expression in the intestinal lumen and cancerous tissue mediated by
      aberrant K-ras signaling. Collectively, the findings a) indicate that interleukin
      expression is influenced by ras signaling and specific interleukins play an
      oncogenic promoter role in colorectal cancer, highlighting the molecular link
      between inflammation and tumorigenesis, and b) accentuate the interwoven
      molecular correlations as leads to new therapeutic approaches in the future. 

PMID- 24040002
TI  - New structural variants of aeruginosin produced by the toxic bloom forming
      cyanobacterium Nodularia spumigena.
AB  - Nodularia spumigena is a filamentous diazotrophic cyanobacterium that forms
      blooms in brackish water bodies. This cyanobacterium produces linear and cyclic
      peptide protease inhibitors which are thought to be part of a chemical defense
      against grazers. Here we show that N. spumigena produces structurally novel
      members of the aeruginosin family of serine protease inhibitors. Extensive
      chemical analyses including NMR demonstrated that the aeruginosins are comprised
      of an N-terminal short fatty acid chain, L-Tyr, L-Choi and L-argininal and in
      some cases pentose sugar. The genome of N. spumigena CCY9414 contains a compact
      18-kb aeruginosin gene cluster encoding a peptide synthetase with a reductive
      release mechanism which offloads the aeruginosins as reactive peptide aldehydes.
      Analysis of the aeruginosin and spumigin gene clusters revealed two different
      strategies for the incorporation of N-terminal protecting carboxylic acids. These
      results demonstrate that strains of N. spumigena produce aeruginosins and
      spumigins, two families of structurally similar linear peptide aldehydes using
      separate peptide synthetases. The aeruginosins were chemically diverse and we
      found 11 structural variants in 16 strains from the Baltic Sea and Australia. Our
      findings broaden the known structural diversity of the aeruginosin peptide family
      to include peptides with rare N-terminal short chain (C2-C10) fatty acid
      moieties. 

PMID- 24040003
TI  - Adaptive evolution of Escherichia coli to an alpha-peptide/beta-peptoid
      peptidomimetic induces stable resistance.
AB  - Antimicrobial peptides (AMPs) and synthetic analogues thereof target conserved
      structures of bacterial cell envelopes and hence, development of resistance has
      been considered an unlikely event. However, recently bacterial resistance to AMPs
      has been observed, and the aim of the present study was to determine whether
      bacterial resistance may also evolve against synthetic AMP analogues, e.g. alpha
      peptide/beta-peptoid peptidomimetics. E. coli ATCC 25922 was exposed to
      increasing concentrations of a peptidomimetic (10 lineages), polymyxin B (10
      lineages), or MilliQ water (4 lineages) in a re-inoculation culturing setup
      covering approx. 500 generations. All 10 lineages exposed to the peptidomimetic
      adapted to 32 * MIC while this occurred for 8 out of 10 of the polymyxin B
      exposed lineages. All lineages exposed to 32 * MIC of either the peptidomimetic
      or polymyxin B had a significantly increased MIC (16-32 *) to the selection
      agent. Five transfers (~ 35 generations) in unsupplemented media did not abolish
      resistance indicating that resistance was heritable. Single isolates from
      peptidomimetic-exposed lineage populations displayed MICs against the
      peptidomimetic from wild-type MIC to 32 * MIC revealing heterogeneous
      populations. Resistant isolates showed no cross-resistance against a panel of
      membrane-active AMPs. These isolates were highly susceptible to blood plasma
      antibacterial activity and were killed when plasma concentrations exceeded ~ 30%.
      Notably, MIC of the peptidomimetic against resistant isolates returned to wild
      type level upon addition of 25% plasma. Whole-genome sequencing of twenty
      isolates from four resistant lineages revealed mutations, in murein
      transglycosylase D (mltD) and outer-membrane proteins, which were conserved
      within and between lineages. However, no common resistance-conferring mutation
      was identified. We hypothesise that alterations in cell envelope structure result
      in peptidomimetic resistance, and that this may occur via several distinct
      mechanisms. Interestingly, this type of resistance result in a concomitant high
      susceptibility towards plasma, and therefore the present study does not infer
      additional concern for peptidomimetics as future therapeutics.

PMID- 24040004
TI  - Magnetic resonance susceptibility-weighted imaging versus other imaging
      modalities in detecting splenic siderotic lesions.
AB  - BACKGROUND: Susceptibility-weighted imaging (SWI) has been proven to be superior
      to T2*-weighted imaging and also other existing magnetic resonance imaging (MRI)
      techniques for the detection of iron content and hemorrhage in the brain. The
      purpose of this study was to compare SWI with T1WI, T2WI and T2*WI in detecting
      splenic siderotic lesions. METHODOLOGY/PRINCIPAL FINDINGS: Twenty-two patients
      with splenic siderotic nodule were imaged with non-contrast MRI T1WI, T2WI, T2*WI
      and SWI at 3.0 Tesla. Imaging data were independently analyzed by two experienced
      radiologists. The number of splenic siderotic nodules was counted, and the size
      (largest diameter) was measured. The conspicuity was calculated as the nodule to
      background parenchyma intensity ratio. We found that SWI detected a larger
      average number of splenic siderotic nodules than T1WI, T2WI, or T2*WI (all
      P<0.05). The average size of the nodules detected by SWI was larger than that of
      those detected by T1WI, T2WI or T2*WI (all P<0.05). SWI provided superior
      contrast and visibility for splenic siderotic nodules compared to any other
      sequence (all P<0.001). CONCLUSIONS: SWI may be a better detection scheme for
      splenic siderotic nodules than T1WI, T2WI and T2*WI.

PMID- 24040005
TI  - Transcriptome sequence and plasmid copy number analysis of the brewery isolate
      Pediococcus claussenii ATCC BAA-344 T during growth in beer.
AB  - Growth of specific lactic acid bacteria in beer leads to spoiled product and
      economic loss for the brewing industry. Microbial growth is typically inhibited
      by the combined stresses found in beer (e.g., ethanol, hops, low pH, minimal
      nutrients); however, certain bacteria have adapted to grow in this harsh
      environment. Considering little is known about the mechanisms used by bacteria to
      grow in and spoil beer, transcriptome sequencing was performed on a variant of
      the beer-spoilage organism Pediococcus claussenii ATCC BAA-344(T) (Pc344-358).
      Illumina sequencing was used to compare the transcript levels in Pc344-358
      growing mid-exponentially in beer to those in nutrient-rich MRS broth. Various
      operons demonstrated high gene expression in beer, several of which are involved
      in nutrient acquisition and overcoming the inhibitory effects of hop compounds.
      As well, genes functioning in cell membrane modification and biosynthesis
      demonstrated significantly higher transcript levels in Pc344-358 growing in beer.
      Three plasmids had the majority of their genes showing increased transcript
      levels in beer, whereas the two cryptic plasmids showed slightly decreased gene
      expression. Follow-up analysis of plasmid copy number in both growth environments
      revealed similar trends, where more copies of the three non-cryptic plasmids were
      found in Pc344-358 growing in beer. Transcriptome sequencing also enabled the
      addition of several genes to the P. claussenii ATCC BAA-344(T) genome annotation,
      some of which are putatively transcribed as non-coding RNAs. The sequencing
      results not only provide the first transcriptome description of a beer-spoilage
      organism while growing in beer, but they also highlight several targets for
      future exploration, including genes that may have a role in the general stress
      response of lactic acid bacteria.

PMID- 24040006
TI  - A comparison of digital gene expression profiling and methyl DNA
      immunoprecipitation as methods for gene discovery in honeybee (Apis mellifera)
      behavioural genomic analyses.
AB  - The honey bee has a well-organized system of division of labour among workers.
      Workers typically progress through a series of discrete behavioural castes as
      they age, and this has become an important case study for exploring how dynamic
      changes in gene expression can influence behaviour. Here we applied both digital
      gene expression analysis and methyl DNA immunoprecipitation analysis to nurse,
      forager and reverted nurse bees (nurses that have returned to the nursing state
      after a period spent foraging) from the same colony in order to compare the
      outcomes of these different forms of genomic analysis. A total of 874 and 710
      significantly differentially expressed genes were identified in forager/nurse and
      reverted nurse/forager comparisons respectively. Of these, 229 genes exhibited
      reversed directions of gene expression differences between the forager/nurse and
      reverted nurse/forager comparisons. Using methyl-DNA immunoprecipitation combined
      with high-throughput sequencing (MeDIP-seq) we identified 366 and 442
      significantly differentially methylated genes in forager/nurse and reverted
      nurse/forager comparisons respectively. Of these, 165 genes were identified as
      differentially methylated in both comparisons. However, very few genes were
      identified as both differentially expressed and differentially methylated in our
      comparisons of nurses and foragers. These findings confirm that changes in both
      gene expression and DNA methylation are involved in the nurse and forager
      behavioural castes, but the different analytical methods reveal quite distinct
      sets of candidate genes. 

PMID- 24040008
TI  - Identification of genes involved in wild crucifer Rorippa indica resistance
      response on mustard aphid Lipaphis erysimi challenge.
AB  - Mustard aphid, Lipaphis erysimi (L.) Kaltenbach is a perpetual annual threat in
      the cultivation of rapeseed- mustard (Brassica spp.) crop in tropical and sub
      tropical climate. Cultivated Brassica germplasm has failed so far to provide any
      source of resistance. Wild germplasm is a potential source of resistance against
      many threatening herbivores. On wild germplasm screening, we noted that the wild
      crucifer Rorippa indica (L.) Hiern confers resistance against L. erysimi. In the
      present study L. erysimi challenged transcriptome of R. indica was compared to un
      infested R. indica sample to get a molecular insight about the aphid resistance
      mechanism and identify the candidate defense response genes. Cloning, sequencing
      and in silico sequence analysis of complimentary DNA amplified fragment length
      polymorphism identified 116 differentially expressed transcript derived fragments
      revealed thirty candidates which are from different functional categories
      including redox regulation, signalling, photosynthesis, structure, metabolism,
      defense response as well as a few of unknown function. Twenty four
      identifications were then studied by quantitative real time RT PCR analysis at 6,
      12, 24 and 48 hour time point post infestation to understand the early-to-late
      defense response through their relative gene expression profiles. Seventeen
      fragments showed significant up or down regulation at p<0.05 level. The response
      was influenced by different phytohormonal signalling pathways simultaneously. The
      candidate defense response expressed sequence tags specifically for the
      resistance genes identified in this study have implication in building desired
      mustard aphid resistance in susceptible rapeseed-mustard plants in future. This
      is the first molecular report on crucifer defense response against mustard aphid
      L. erysimi. 

PMID- 24040007
TI  - Human fMRI reveals that delayed action re-recruits visual perception.
AB  - Behavioral and neuropsychological research suggests that delayed actions rely on
      different neural substrates than immediate actions; however, the specific brain
      areas implicated in the two types of actions remain unknown. We used functional
      magnetic resonance imaging (fMRI) to measure human brain activation during
      delayed grasping and reaching. Specifically, we examined activation during visual
      stimulation and action execution separated by a 18-s delay interval in which
      subjects had to remember an intended action toward the remembered object. The
      long delay interval enabled us to unambiguously distinguish visual, memory
      related, and action responses. Most strikingly, we observed reactivation of the
      lateral occipital complex (LOC), a ventral-stream area implicated in visual
      object recognition, and early visual cortex (EVC) at the time of action.
      Importantly this reactivation was observed even though participants remained in
      complete darkness with no visual stimulation at the time of the action. Moreover,
      within EVC, higher activation was observed for grasping than reaching during both
      vision and action execution. Areas in the dorsal visual stream were activated
      during action execution as expected and, for some, also during vision. Several
      areas, including the anterior intraparietal sulcus (aIPS), dorsal premotor cortex
      (PMd), primary motor cortex (M1) and the supplementary motor area (SMA), showed
      sustained activation during the delay phase. We propose that during delayed
      actions, dorsal-stream areas plan and maintain coarse action goals; however, at
      the time of execution, motor programming requires re-recruitment of detailed
      visual information about the object through reactivation of (1) ventral-stream
      areas involved in object perception and (2) early visual areas that contain
      richly detailed visual representations, particularly for grasping. 

PMID- 24040009
TI  - MLL becomes functional through intra-molecular interaction not by proteolytic
      processing.
AB  - The mixed lineage leukemia (MLL) protein is an epigenetic transcriptional
      regulator that controls proliferative expansion of immature hematopoietic
      progenitors, whose aberrant activation triggers leukemogenesis. A mature MLL
      protein is produced by formation of an intra-molecular complex and proteolytic
      cleavage. However the biological significance of these two post-transcriptional
      events remains unclear. To address their in vivo roles, mouse mutant alleles were
      created that exclusively express either a variant protein incapable of intra
      molecular interaction (designated de) or an uncleavable mutant protein
      (designated uc). The de homozygous mice died during midgestation and manifested
      devastating failure in embryonic development and reduced numbers of hematopoietic
      progenitors, whereas uc homozygous mice displayed no apparent defects. Expression
      of MLL target genes was severely impaired in de homozygous fibroblasts but
      unaffected in uc homozygous fibroblasts. These results unequivocally demonstrate
      that intra-molecular complex formation is a crucial maturation step whereas
      proteolytic cleavage is dispensable for MLL-dependent gene activation and
      proliferation in vivo. 

PMID- 24040010
TI  - Glutathione--hydroxyl radical interaction: a theoretical study on radical
      recognition process.
AB  - Non-reactive, comparative (2 * 1.2 MUs) molecular dynamics simulations were
      carried out to characterize the interactions between glutathione (GSH, host
      molecule) and hydroxyl radical (OH(*), guest molecule). From this analysis, two
      distinct steps were identified in the recognition process of hydroxyl radical by
      glutathione: catching and steering, based on the interactions between the host
      guest molecules. Over 78% of all interactions are related to the catching
      mechanism via complex formation between anionic carboxyl groups and the OH
      radical, hence both terminal residues of GSH serve as recognition sites. The
      glycine residue has an additional role in the recognition of OH radical, namely
      the steering. The flexibility of the Gly residue enables the formation of further
      interactions of other parts of glutathione (e.g. thiol, alpha- and beta-carbons)
      with the lone electron pair of the hydroxyl radical. Moreover, quantum chemical
      calculations were carried out on selected GSH/OH(*) complexes and on appropriate
      GSH conformers to describe the energy profile of the recognition process. The
      relative enthalpy and the free energy changes of the radical recognition of the
      strongest complexes varied from -42.4 to -27.8 kJ/mol and from -21.3 to 9.8
      kJ/mol, respectively. These complexes, containing two or more intermolecular
      interactions, would be the starting configurations for the hydrogen atom
      migration to quench the hydroxyl radical via different reaction channels.

PMID- 24040011
TI  - Muricholic acids inhibit Clostridium difficile spore germination and growth.
AB  - Infections caused by Clostridium difficile have increased steadily over the past
      several years. While studies on C. difficile virulence and physiology have been
      hindered, in the past, by lack of genetic approaches and suitable animal models,
      newly developed technologies and animal models allow these processes to be
      studied in detail. One such advance is the generation of a mouse-model of C.
      difficile infection. The development of this system is a major step forward in
      analyzing the genetic requirements for colonization and infection. While
      important, it is equally as important in understanding what differences exist
      between mice and humans. One of these differences is the natural bile acid
      composition. Bile acid-mediated spore germination is an important step in C.
      difficile colonization. Mice produce several different bile acids that are not
      found in humans. These muricholic acids have the potential to impact C. difficile
      spore germination. Here we find that the three muricholic acids (alpha-muricholic
      acid, beta-muricholic acid and omega-muricholic acid) inhibit C. difficile spore
      germination and can impact the growth of vegetative cells. These results
      highlight an important difference between humans and mice and may have an impact
      on C. difficile virulence in the mouse-model of C. difficile infection. 

PMID- 24040012
TI  - Suramin: a potential therapy for diabetic nephropathy.
AB  - OBJECTIVE: To determine whether delayed administration of a single dose of
      suramin, a drug that has been used extensively in humans to treat
      trypanosomiasis, attenuates renal injury in a leptin receptor deficient C57BLKS/J
      db/db type 2 diabetic nephropathy (T2DN) mouse model. RESEARCH DESIGN AND
      METHODS: Groups of female non-diabetic (control) db/m and diabetic db/db mice of
      8 and 16 weeks of age, respectively, were treated with suramin (10 mg/kg) or
      saline i.v. All animals were euthanized one week later. Measurements in mice 1
      week following treatment included the following: body weight; blood glucose;
      urinary protein excretion; pathological lesions in glomeruli and proximal
      tubules; changes in protein expression of pro-inflammatory transcription factor
      nuclear factor kappaB (NF-kappaB) and intracellular adhesion molecule-1 (ICAM-1),
      profibrotic transforming growth factor-beta1 (TGF-beta1), phospho-SMAD-3 and
      alpha-smooth muscle actin (alpha-SMA); and immunohistochemical analysis of
      leukocyte infiltration and collagen 1A2 (COL1A2) deposition. RESULTS: Immunoblot
      analysis revealed increased NF-kappaB, ICAM-1, TGF-beta1, phospho-SMAD-3, and
      alpha-SMA proteins in both 9 and 17 week db/db mice as compared to db/m control
      mice. Immunohistochemical analysis revealed moderate leukocyte infiltration and
      collagen 1A2 (COL1A2) deposition in 9 week db/db mice that was increased in the
      17 week db/db mice. Importantly, suramin significantly decreased expression of
      all these markers in 9 week db/db mice and partially decreased in 17 week db/db
      mice without altering body weight, blood glucose or urinary protein excretion.
      There was no difference in creatinine clearance between 9 week db/m and db/db
      mice +/- suramin. Importantly, in the 17 week db/db mice suramin intervention
      reversed the impaired creatinine clearance and overt histological damage.
      CONCLUSIONS: Delayed administration of a single dose of suramin in a model of
      T2DN attenuated inflammation and fibrosis as well as improved renal function,
      supporting the use of suramin in T2DN.

PMID- 24040013
TI  - Use of recombinant tobacco mosaic virus to achieve RNA interference in plants
      against the citrus mealybug, Planococcus citri (Hemiptera: Pseudococcidae).
AB  - The citrus mealybug, Planococcus citri, is an important plant pest with a very
      broad plant host range. P. citri is a phloem feeder and loss of plant vigor and
      stunting are characteristic symptoms induced on a range of host plants, but P.
      citri also reduces fruit quality and causes fruit drop leading to significant
      yield reductions. Better strategies for managing this pest are greatly needed.
      RNA interference (RNAi) is an emerging tool for functional genomics studies and
      is being investigated as a practical tool for highly targeted insect control.
      Here we investigated whether RNAi effects can be induced in P. citri and whether
      candidate mRNAs could be identified as possible targets for RNAi-based P. citri
      control. RNAi effects were induced in P. citri, as demonstrated by specific
      target reductions of P. citri actin, chitin synthase 1 and V-ATPase mRNAs after
      injection of the corresponding specific double-stranded RNA inducers. We also
      used recombinant Tobacco mosaic virus (TMV) to express these RNAi effectors in
      Nicotiana benthamiana plants. We found that P. citri showed lower fecundity and
      pronounced death of crawlers after feeding on recombinant TMV-infected plants.
      Taken together, our data show that actin, chitin synthase 1 and V-ATPase mRNAs
      are potential targets for RNAi against P. citri, and that recombinant TMV is an
      effective tool for evaluating candidate RNAi effectors in plants. 

PMID- 24040014
TI  - beta-Diversity of functional groups of woody plants in a tropical dry forest in
      Yucatan.
AB  - Two main theories have attempted to explain variation in plant species
      composition (beta-diversity). Niche theory proposes that most of the variation is
      related to environment (environmental filtering), whereas neutral theory posits
      that dispersal limitation is the main driver of beta-diversity. In this study, we
      first explored how alpha- and beta-diversity of plant functional groups defined
      by growth form (trees, shrubs and lianas, which represent different strategies of
      resource partitioning), and dispersal syndrome (autochory, anemochory and
      zoochory, which represent differences in dispersal limitation) vary with
      successional age and topographic position in a tropical dry forest. Second, we
      examined the effects of environmental, spatial, and spatially-structured
      environmental factors on beta-diversity of functional groups; we used the spatial
      structure of sampling sites as a proxy for dispersal limitation, and elevation,
      soil properties and forest stand age as indicators of environmental filtering. We
      recorded 200 species and 22,245 individuals in 276 plots; 120 species were trees,
      41 shrubs and 39 lianas. We found that beta-diversity was highest for shrubs,
      intermediate for lianas and lowest for trees, and was slightly higher for
      zoochorous than for autochorous and anemochorous species. All three dispersal
      syndromes, trees and shrubs varied in composition among vegetation classes
      (successional age and topographic position), whilst lianas did not. beta
      diversity was influenced mostly by proxies of environmental filtering, except for
      shrubs, for which the influence of dispersal limitation was more important. Stand
      age and topography significantly influenced alpha-diversity across functional
      groups, but showed a low influence on beta-diversity -possibly due to the
      counterbalancing effect of resprouting on plant distribution and composition. Our
      results show that considering different plant functional groups reveals important
      differences in both alpha- and beta-diversity patterns and correlates that are
      not apparent when focusing on overall woody plant diversity, and that have
      important implications for ecological theory and biodiversity conservation. 

PMID- 24040015
TI  - Survey of Bartonella spp. in U.S. bed bugs detects Burkholderia multivorans but
      not Bartonella.
AB  - Bed bugs (Cimex lectularius L.) have resurged in the United States and globally.
      Bed bugs are hematophagous ectoparasites of humans and other animals, including
      domestic pets, chickens, and bats, and their blood feeding habits contribute to
      their potential as disease vectors. Several species of Bartonella are re-emergent
      bacterial pathogens that also affect humans, domestic pets, bats and a number of
      other wildlife species. Because reports of both bed bugs and Bartonella have been
      increasing in the U.S., and because their host ranges can overlap, we
      investigated whether the resurgences of these medically important pathogens and
      their potential vector might be linked, by screening for Bartonella spp. in bed
      bugs collected from geographic areas where these pathogens are prevalent and from
      bed bugs that have been in culture in the laboratory for several years. We
      screened a total of 331 bed bugs: 316 bed bugs from 36 unique collections in 29
      geographic locations in 13 states, 10 bed bugs from two colonies maintained in
      the laboratory for 3 yr, and 5 bed bugs from a colony that has been in culture
      since before the recent resurgence of bed bugs. Bartonella spp. DNA was screened
      using a polymerase chain reaction assay targeting the 16S-23S rRNA intergenic
      transcribed spacer region. Bartonella DNA was not amplified from any bed bug, but
      five bed bugs from four different apartments of an elderly housing building in
      North Carolina contained DNA sequences that corresponded to Burkholderia
      multivorans, an important pathogen in nosocomial infections that was not
      previously linked to an arthropod vector. 

PMID- 24040016
TI  - Regulation of hippocampal cGMP levels as a candidate to treat cognitive deficits
      in Huntington's disease.
AB  - Huntington's disease (HD) patients and mouse models show learning and memory
      impairment associated with hippocampal dysfunction. The neuronal nitric oxide
      synthase/3',5'-cyclic guanosine monophosphate (nNOS/cGMP) pathway is implicated
      in synaptic plasticity, and in learning and memory processes. Here, we examined
      the nNOS/cGMP pathway in the hippocampus of HD mice to determine whether it can
      be a good therapeutic target for cognitive improvement in HD. We analyzed
      hippocampal nNOS and phosphodiesterase (PDE) 5 and 9 levels in R6/1 mice, and
      cGMP levels in the hippocampus of R6/1, R6/2 and Hdh(Q7/Q111) mice, and of HD
      patients. We also investigated whether sildenafil, a PDE5 inhibitor, could
      improve cognitive deficits in R6/1 mice. We found that hippocampal cGMP levels
      were 3-fold lower in 12-week-old R6/1 mice, when they show deficits in object
      recognition memory and in passive avoidance learning. Consistent with hippocampal
      cGMP levels, nNOS levels were down-regulated, while there were no changes in the
      levels of PDE5 and PDE9 in R6/1 mice. A single intraperitoneal injection of
      sildenafil (3 mg/Kg) immediately after training increased cGMP levels, and
      improved memory in R6/1 mice, as assessed by using the novel object recognition
      and the passive avoidance test. Importantly, cGMP levels were also reduced in
      R6/2 mouse and human HD hippocampus. Therefore, the regulation of hippocampal
      cGMP levels can be a suitable treatment for cognitive impairment in HD. 

PMID- 24040017
TI  - Distribution of bone-marrow-derived endothelial and immune cells in a murine
      colitis-associated colorectal cancer model.
AB  - Inflammatory bowel disease (IBD) can lead to an increased risk of developing
      colorectal cancer (CRC). The aim of this study was to establish a model for
      combined bone marrow transplantation (BMT) and colitis-associated colorectal
      cancer (CAC) and to define the contribution of BM-derived cells during the
      inflammation associated with carcinogenesis. We established a model for BMT using
      green fluorescent protein (GFP) transgenic mice, followed by AOM/DSS-induced CAC,
      and performed confocal microscopy analysis on in vivo living tissue and frozen
      tumor sections. Our imaging analyses showed that GFP-positive cells extensively
      infiltrated the tumor stroma and that some WGA and GFP or CD31 and GFP double
      positive cells were observed in the lining of tumor vessels. Flow cytometry
      analysis of the tumor-infiltrating cells showed that the GFP-positive CD11c+ DCs
      cells were one-third of the GFP+/CD11C- cells, and that half of these DCs (0.96%
      vs 1.02%) were GFP-positive BM-derived cells. The majority of CD4(+) T cells were
      GFP-negative (12.02% vs 1.9%), and we discovered a novel CD4(+) CD11c(+) DC
      subset (0.34% vs 1.64%). In conclusion, we defined the distribution of BM-derived
      endothelial cells, CD11c(+) DCs and CD4(+) T cells in tumors. This model might be
      useful for elucidating the diverse BM-derived cell types and functions during the
      progression of colitis-associated colorectal cancer. 

PMID- 24040018
TI  - The long coiled-coil protein NECC2 is associated to caveolae and modulates
      NGF/TrkA signaling in PC12 cells [corrected].
AB  - TrkA-mediated NGF signaling in PC12 cells has been shown to be compartimentalized
      in specialized microdomains of the plasma membrane, the caveolae, which are
      organized by scaffold proteins including the member of the caveolin family of
      proteins, caveolin-1. Here, we characterize the intracellular distribution as
      well as the biochemical and functional properties of the neuroendocrine long
      coiled-coil protein 2 (NECC2), a novel long coiled-coil protein selectively
      expressed in neuroendocrine tissues that contains a predicted caveolin-binding
      domain and displays structural characteristics of a scaffolding factor. NECC2
      distributes in caveolae, wherein it colocalizes with the TrkA receptor, and
      behaves as a caveolae-associated protein in neuroendocrine PC12 cells. In
      addition, stimulation of PC12 cells with nerve growth factor (NGF) increased the
      expression and regulated the distribution of NECC2. Interestingly, knockdown as
      well as overexpression of NECC2 resulted in a reduction of NGF-induced
      phosphorylation of the TrkA downstream effector extracellular signal-regulated
      kinases 1 and 2 (ERK1/ERK2) but not of Akt. Altogether, our results identify
      NECC2 as a novel component of caveolae in PC12 cells and support the contribution
      of this protein in the maintenance of TrkA-mediated NGF signaling. 

PMID- 24040019
TI  - Synergistic apoptosis of CML cells by buthionine sulfoximine and hydroxychavicol
      correlates with activation of AIF and GSH-ROS-JNK-ERK-iNOS pathway.
AB  - BACKGROUND: Hydroxychavicol (HCH), a constituent of Piper betle leaf has been
      reported to exert anti-leukemic activity through induction of reactive oxygen
      species (ROS). The aim of the study is to optimize the oxidative stress -induced
      chronic myeloid leukemic (CML) cell death by combining glutathione synthesis
      inhibitor, buthionine sulfoximine (BSO) with HCH and studying the underlying
      mechanism. MATERIALS AND METHODS: Anti-proliferative activity of BSO and HCH
      alone or in combination against a number of leukemic (K562, KCL22, KU812, U937,
      Molt4), non-leukemic (A549, MIA-PaCa2, PC-3, HepG2) cancer cell lines and normal
      cell lines (NIH3T3, Vero) was measured by MTT assay. Apoptotic activity in CML
      cell line K562 was detected by flow cytometry (FCM) after staining with annexin V
      FITC/propidium iodide (PI), detection of reduced mitochondrial membrane potential
      after staining with JC-1, cleavage of caspase- 3 and poly (ADP)-ribose polymerase
      proteins by western blot analysis and translocation of apoptosis inducing factor
      (AIF) by confocal microscopy. Intracellular reduced glutathione (GSH) was
      measured by colorimetric assay using GSH assay kit. 2',7'
      dichlorodihydrofluorescein diacetate (DCF-DA) and 4-amino-5-methylamino-2',7'
      difluorofluorescein (DAF-FM) were used as probes to measure intracellular
      increase in ROS and nitric oxide (NO) levels respectively. Multiple techniques
      like siRNA transfection and pharmacological inhibition were used to understand
      the mechanisms of action. RESULTS: Non-apoptotic concentrations of BSO
      significantly potentiated HCH-induced apoptosis in K562 cells. BSO potentiated
      apoptosis-inducing activity of HCH in CML cells by caspase-dependent as well as
      caspase-independent but apoptosis inducing factor (AIF)-dependent manner.
      Enhanced depletion of intracellular GSH induced by combined treatment correlated
      with induction of ROS. Activation of ROS- dependent JNK played a crucial role in
      ERK1/2 activation which subsequently induced the expression of inducible nitric
      oxide synthase (iNOS). iNOS- mediated production of NO was identified as an
      effector molecule causing apoptosis of CML cells. CONCLUSION/SIGNIFICANCE: BSO
      synergizes with HCH in inducing apoptosis of CML cells through the GSH-ROS-JNK
      ERK-iNOS pathway.

PMID- 24040020
TI  - Evaluating the feasibility and participants' representativeness of an online
      nationwide surveillance system for influenza in France.
AB  - The increasing Internet coverage and the widespread use of digital devices offer
      the possibility to develop new digital surveillance systems potentially capable
      to provide important aid to epidemiological and public health monitoring and
      research. In France, a new nationwide surveillance system for influenza-like
      illness, GrippeNet.fr, was introduced since the 2011/2012 season based on an
      online participatory mechanism and open to the general population. We evaluate
      the recruitment and participation of users to the first pilot season with respect
      to similar efforts in Europe to assess the feasibility of establishing a
      participative network of surveillance in France. We further investigate the
      representativeness of the GrippeNet.fr population along a set of indicators on
      geographical, demographic, socio-economic and health aspects. Participation was
      widespread in the country and with rates comparable to other European countries
      with partnered projects running since a longer time. It was not representative of
      the general population in terms of age and gender, however all age classes were
      represented, including the older classes (65+ years old), generally less familiar
      with the digital world, but considered at high risk for influenza complications.
      Once adjusted on demographic indicators, the GrippeNet.fr population is found to
      be more frequently employed, with a higher education level and vaccination rate
      with respect to the general population. A similar propensity to commute for work
      to different regions was observed, and no significant difference was found for
      asthma and diabetes. Results show the feasibility of the system, provide
      indications to inform adjusted epidemic analyses, and highlight the presence of
      specific population groups that need to be addressed by targeted communication
      strategies to achieve a higher representativeness in the following seasons. 

PMID- 24040021
TI  - Urban economies and occupation space: can they get "there" from "here"?
AB  - Much of the socioeconomic life in the United States occurs in its urban areas.
      While an urban economy is defined to a large extent by its network of
      occupational specializations, an examination of this important network is absent
      from the considerable body of work on the determinants of urban economic
      performance. Here we develop a structure-based analysis addressing how the
      network of interdependencies among occupational specializations affects the ease
      with which urban economies can transform themselves. While most occupational
      specializations exhibit positive relationships between one another, many exhibit
      negative ones, and the balance between the two partially explains the
      productivity of an urban economy. The current set of occupational specializations
      of an urban economy and its location in the occupation space constrain its future
      development paths. Important tradeoffs exist between different alternatives for
      altering an occupational specialization pattern, both at a single occupation and
      an entire occupational portfolio levels. 

PMID- 24040022
TI  - Identification of the porcine XIST gene and its differential CpG methylation
      status in male and female pig cells.
AB  - XIST, a long non-coding RNA, plays an important role in triggering X chromosome
      inactivation in eutherians, and is used extensively for qualifying stem cells and
      cloned embryos. However, a porcine XIST has not yet been thoroughly identified
      despite its biological importance in a wide variety of research fields. Here, we
      present a full-length porcine XIST sequence assembled using known sequences
      (GenBank), RNA-Seq data (NCBI SRA), and PCR/sequencing. The proposed porcine XIST
      gene model encodes a 25,215-bp transcript consisting of 7 exons, including two
      conserved and two porcine-specific repeat regions. Transcription covering the
      entire XIST region was observed specifically in female cells, but not in male
      cells. We also identified eight transcription starting sites (TSSs) and evaluated
      CpG methylation patterns in the upstream (+2.0 kb) and downstream (-2.0 kb)
      regions. Sixty-seven CG di-nucleotides identified in the target region were
      considered to be candidate CpG sites, and were enriched in the following two
      regions: -284 to +53 bp (13 sites) and +285 to +1,727 bp (54 sites) from the
      selected TSS. Male 5' region of XIST (64.5 sites, 96.26%) had a higher level of
      CpG methylation than female DNA (33.4 sites, 49.85%). Taken together, our results
      revealed that the porcine XIST gene is expressed exclusively in female cells,
      which is influenced by the lower level of CpG methylation in the putative
      promoter region compared with male cells. The porcine XIST presented in this
      study represents a useful tool for related research areas such as porcine
      embryology and stem cell biology. 

PMID- 24040023
TI  - Evidence against a beneficial effect of irisin in humans.
AB  - Brown adipose tissue has gained interest as a potential target to treat obesity
      and metabolic diseases. Irisin is a newly identified hormone secreted from
      skeletal muscle enhancing browning of white fat cells, which improves systemic
      metabolism by increasing energy expenditure in mice. The discovery of irisin
      raised expectations of its therapeutic potential to treat metabolic diseases.
      However, the effect of irisin in humans is unclear. Analyses of genomic DNA, mRNA
      and expressed sequence tags revealed that FNDC5, the gene encoding the precursor
      of irisin, is present in rodents and most primates, but shows in humans a
      mutation in the conserved start codon ATG to ATA. HEK293 cells transfected with a
      human FNDC5 construct with ATA as start codon resulted in only 1% full-length
      protein compared to human FNDC5 with ATG. Additionally, in vitro contraction of
      primary human myotubes by electrical pulse stimulation induced a significant
      increase in PGC1alpha mRNA expression. However, FNDC5 mRNA level was not altered.
      FNDC5 mRNA expression in muscle biopsies from two different human exercise
      studies was not changed by endurance or strength training. Preadipocytes isolated
      from human subcutaneous adipose tissue exhibited differentiation to brite human
      adipocytes when incubated with bone morphogenetic protein (BMP) 7, but neither
      recombinant FNDC5 nor irisin were effective. In conclusion, our findings suggest
      that it is rather unlikely that the beneficial effect of irisin observed in mice
      can be translated to humans. 

PMID- 24040024
TI  - mtDNA from the early Bronze Age to the Roman period suggests a genetic link
      between the Indian subcontinent and Mesopotamian cradle of civilization.
AB  - Ancient DNA methodology was applied to analyse sequences extracted from freshly
      unearthed remains (teeth) of 4 individuals deeply deposited in slightly alkaline
      soil of the Tell Ashara (ancient Terqa) and Tell Masaikh (ancient Kar
      Assurnasirpal) Syrian archaeological sites, both in the middle Euphrates valley.
      Dated to the period between 2.5 Kyrs BC and 0.5 Kyrs AD the studied individuals
      carried mtDNA haplotypes corresponding to the M4b1, M49 and/or M61 haplogroups,
      which are believed to have arisen in the area of the Indian subcontinent during
      the Upper Paleolithic and are absent in people living today in Syria. However,
      they are present in people inhabiting today's Tibet, Himalayas, India and
      Pakistan. We anticipate that the analysed remains from Mesopotamia belonged to
      people with genetic affinity to the Indian subcontinent since the distribution of
      identified ancient haplotypes indicates solid link with populations from the
      region of South Asia-Tibet (Trans-Himalaya). They may have been descendants of
      migrants from much earlier times, spreading the clades of the macrohaplogroup M
      throughout Eurasia and founding regional Mesopotamian groups like that of Terqa
      or just merchants moving along trade routes passing near or through the region.
      None of the successfully identified nuclear alleles turned out to be DeltaF508
      CFTR, LCT-13910T or Delta32 CCR5. 

PMID- 24040025
TI  - Candidate microRNA biomarkers in human gastric cancer: a systematic review and
      validation study.
AB  - Gastric cancer (GC) remains a major cause of morbidity and mortality worldwide
      and there is therefore a clear need to search for more sensitive early diagnostic
      biomarkers. We performed a systematic review of eight published miRNA profiling
      studies that compared GC tissues with adjacent noncancerous tissues. A miRNA
      ranking system was used that took the frequency of comparisons, direction of
      differential expression and total sample size into consideration. We identified
      five miRNAs that were most consistently reported to be upregulated (miR-21, miR
      106b, miR-17, miR-18a and miR-20a) and two miRNAs that were downregulated (miR
      378 and miR-638). Six of these were further validated in 32 paired sets of GC and
      adjacent noncancerous tissue samples using real-time PCR. MiR-21, miR-106b, miR
      17, miR-18a and miR-20a were confirmed to be upregulatedin GC tissues, while the
      expression of miR-378 was decreased. Moreover, we found a significant association
      between expression levels of miR-21, miR-106b, miR-17, miR-18a and miR-20a and
      clinicopathological features of GC. These miRNAs may be used for diagnostic
      and/or prognostic biomarkers for GC and therefore warrant further investigation. 

PMID- 24040026
TI  - Slipping through the cracks: rubber plantation is unsuitable breeding habitat for
      frogs in Xishuangbanna, China.
AB  - Conversion of tropical forests into agriculture may present a serious risk to
      amphibian diversity if amphibians are not able to use agricultural areas as
      habitat. Recently, in Xishuangbanna Prefecture, Yunnan Province - a hotspot of
      frog diversity within China - two-thirds of the native tropical rainforests have
      been converted into rubber plantation agriculture. We conducted surveys and
      experiments to quantify habitat use for breeding and non-breeding life history
      activities of the native frog species in rainforest, rubber plantation and other
      human impacted sites. Rubber plantation sites had the lowest species richness in
      our non-breeding habitat surveys and no species used rubber plantation sites as
      breeding habitat. The absence of breeding was likely not due to intrinsic
      properties of the rubber plantation pools, as our experiments indicated that
      rubber plantation pools were suitable for tadpole growth and development. Rather,
      the absence of breeding in the rubber plantation was likely due to a misalignment
      of breeding and non-breeding habitat preferences. Analyses of our breeding
      surveys showed that percent canopy cover over pools was the strongest
      environmental variable influencing breeding site selection, with species
      exhibiting preferences for pools under both high and low canopy cover. Although
      rubber plantation pools had high canopy cover, the only species that bred in high
      canopy cover sites used the rainforest for both non-breeding and breeding
      activities, completing their entire life cycle in the rainforest. Conversely, the
      species that did use the rubber plantation for non-breeding habitat preferred to
      breed in low canopy sites, also avoiding breeding in the rubber plantation.
      Rubber plantations are likely an intermediate habitat type that 'slips through
      the cracks' of species habitat preferences and is thus avoided for breeding. In
      summary, unlike the rainforests they replaced, rubber plantations alone may not
      be able to support frog populations. 

PMID- 24040027
TI  - Dynamic proteomics of nucleus accumbens in response to acute psychological stress
      in environmentally enriched and isolated rats.
AB  - Our prior research has shown that environmental enrichment (i.e. rats reared in
      an environment with novel objects, social contact with conspecifics) produces a
      protective antidepressant-like phenotype in rats and decreases neurobiological
      effects of acute psychological stress. Although CREB activity has been identified
      as a major player, the downstream molecular mechanisms remain largely unexplored.
      Thus, the current study investigates proteomic differences in the accumbens of
      rats raised in an enriched condition (EC) versus those raised in an isolated
      control condition (IC) under basal conditions and after 30 min of acute restraint
      stress. Results showed that under basal conditions, EC rats generally expressed
      less mitochondria-related proteins, particularly those involved in TCA cycle and
      electron transport compared to IC rats. After 30 min of acute stress, EC rats
      displayed increased expression of energy metabolism enzymes (among others) while
      IC rats exhibited decreased expression of similar proteins. Further, network and
      pathway analyses also identified links to AKT signaling proteins, 14-3-3 family
      proteins, heat-shock proteins, and ubiquitin-interacting proteins. The protein
      ENO1 showed marked differential expression and regulation; EC rats expressed
      higher levels under basal conditions that increased subsequent to stress, while
      the basal IC expression was lower and decreased further still after stress. The
      results of this study define differential protein expression in a protective rat
      model for major depression and additionally identify a dynamic and coordinated
      differential response to acute stress between the two groups. These results
      provide new avenues for exploration of the molecular determinants of depression
      and the response to acute stress. 

PMID- 24040028
TI  - Circadian regulation of the Na+/K+-ATPase alpha subunit in the visual system is
      mediated by the pacemaker and by retina photoreceptors in Drosophila
      melanogaster.
AB  - We investigated the diurnal oscillation in abundance of the catalytic alpha
      subunit of the sodium/potassium pump (ATPalpha) in the brain of Drosophila
      melanogaster. This rhythm is bimodal and is particularly robust in the glia cells
      of the lamina, the first optic neuropil. We observed loss of ATPalpha cycling in
      lamina glia in behaviourally arrhythmic per(01) and tim(01) mutants and in flies
      overexpressing the pro-apoptotic gene hid in the PDF-positive clock neurons.
      Moreover, the rhythm of ATPalpha abundance was altered in cry(01) and Pdf(0)
      mutants, in flies with a weakened clock mechanism in retina photoreceptor cells
      and in those subject to downregulation of the neuropeptide ITP by RNAi. This
      complex, rhythmic regulation of the alpha subunit suggests that the
      sodium/potassium pump may be a key target of the circadian pacemaker to impose
      daily control on brain activities, such as rhythmic changes in neuronal
      plasticity, which are best observed in the visual system. 

PMID- 24040029
TI  - Impacts of human disturbance on large prey species: do behavioral reactions
      translate to fitness consequences?
AB  - Anthropogenic disturbances have been demonstrated to affect animal behavior,
      distribution, and abundance, but assessment of their impacts on fitness-related
      traits has received little attention. We hypothesized that human activities and
      infrastructure cause a decrease in the individual performance of preys because of
      anthropogenically enhanced predation risk. We evaluated the impacts of commercial
      logging and road networks on the fitness of a large herbivore known to be
      sensitive to human disturbance: the forest-dwelling woodland caribou (Rangifer
      tarandus caribou). For 8 consecutive years (2004-2011) we monitored 59
      individuals using GPS telemetry in the Charlevoix region of Quebec, Canada. We
      also used Very High Frequency telemetry locations collected on 28 individuals
      from 1999-2000. We related habitat selection of adult caribou at various spatio
      temporal scales to their probability of dying from predation, and to indices of
      their reproductive success and energy expenditure. The probability that adult
      caribou died from predation increased with the proportion of recent disturbances
      (including cutblocks <= 5 years old) in their annual home range. The respective
      effects of increasing paved and forestry road densities depended upon the overall
      road density within the home range of caribou. At a finer scale of 10 to 15 days
      before their death, caribou that were killed by a predator selected for recent
      disturbances more than individuals that survived, and avoided old mature conifer
      stands. The home range area of caribou increased with road density. Finally, the
      composition of the home range of females had no effect on their reproductive
      success. We show that human activities and infrastructure may influence the
      individual performance of large prey species in highly managed regions. We
      outline the need to consider the full set of impacts that human development may
      have on threatened animal populations, with particular emphasis on predator-prey
      relationships and population dynamics.

PMID- 24040031
TI  - Sibling configuration predicts individual and descendant socioeconomic success in
      a modern post-industrial society.
AB  - Growing up with many siblings, at least in the context of modern post-industrial
      low fertility, low mortality societies, is predictive of relatively poor
      performance on school tests in childhood, lower levels of educational attainment,
      and lower income throughout adulthood. Recent studies further indicate these
      relationships hold across generations, so that the descendants of those who grow
      up with many siblings are also at an apparent socioeconomic disadvantage. In this
      paper we add to this literature by considering whether such relationships
      interact with the sex and relative age of siblings. To do this we utilise a
      unique Swedish multigenerational birth cohort study that provides sibling
      configuration data on over 10,000 individuals born in 1915-1929, plus all their
      direct genetic descendants to the present day. Adjusting for parental and birth
      characteristics, we find that the 'socioeconomic cost' of growing up in a large
      family is independent of both the sex of siblings and the sex of the individual.
      However, growing up with several older as opposed to several younger siblings is
      predictive of relatively poor performance on school tests and a lower likelihood
      of progression to tertiary education. This later-born disadvantage also holds
      across generations, with the children of those with many older siblings achieving
      lower levels of educational attainment. Despite these differences, we find that
      while individual and descendant income is negatively related to the number of
      siblings, it is not influenced by the relative age of siblings. Thus, our
      findings imply that the educational disadvantage of later-born children,
      demonstrated here and in numerous other studies, does not necessarily translate
      into reduced earnings in adulthood. We discuss potential explanations for this
      pattern of results, and consider some important directions for future research
      into sibling configuration and wellbeing in modern societies. 

PMID- 24040030
TI  - Plin2 inhibits cellular glucose uptake through interactions with SNAP23, a SNARE
      complex protein.
AB  - Although a link between excess lipid storage and aberrant glucose metabolism has
      been recognized for many years, little is known what role lipid storage droplets
      and associated proteins such as Plin2 play in managing cellular glucose levels.
      To address this issue, the influence of Plin2 on glucose uptake was examined
      using 2-NBD-Glucose and [(3)H]-2-deoxyglucose to show that insulin-mediated
      glucose uptake was decreased 1.7- and 1.8-fold, respectively in L cell
      fibroblasts overexpressing Plin2. Conversely, suppression of Plin2 levels by RNAi
      mediated knockdown increased 2-NBD-Glucose uptake several fold in transfected L
      cells and differentiated 3T3-L1 cells. The effect of Plin2 expression on proteins
      involved in glucose uptake and transport was also examined. Expression of the
      SNARE protein SNAP23 was increased 1.6-fold while levels of syntaxin-5 were
      decreased 1.7-fold in Plin2 overexpression cells with no significant changes
      observed in lipid droplet associated proteins Plin1 or FSP27 or with the insulin
      receptor, GLUT1, or VAMP4. FRET experiments revealed a close proximity of Plin2
      to SNAP23 on lipid droplets to within an intramolecular distance of 51 A. The
      extent of targeting of SNAP23 to lipid droplets was determined by co-localization
      and co-immunoprecipitation experiments to show increased partitioning of SNAP23
      to lipid droplets when Plin2 was overexpressed. Taken together, these results
      suggest that Plin2 inhibits glucose uptake by interacting with, and regulating
      cellular targeting of SNAP23 to lipid droplets. In summary, the current study for
      the first time provides direct evidence for the role of Plin2 in mediating
      cellular glucose uptake. 

PMID- 24040032
TI  - The population structure and diversity of eggplant from Asia and the
      Mediterranean Basin.
AB  - A collection of 238 eggplant breeding lines, heritage varieties and selections
      within local landraces provenanced from Asia and the Mediterranean Basin was
      phenotyped with respect to key plant and fruit traits, and genotyped using 24
      microsatellite loci distributed uniformly throughout the genome. STRUCTURE
      analysis based on the genotypic data identified two major sub-groups, which to a
      large extent mirrored the provenance of the entries. With the goal to identify
      true-breeding types, 38 of the entries were discarded on the basis of
      microsatellite-based residual heterozygosity, along with a further nine which
      were not phenotypically uniform. The remaining 191 entries were scored for a set
      of 19 fruit and plant traits in a replicated experimental field trial. The
      phenotypic data were subjected to principal component and hierarchical principal
      component analyses, allowing three major morphological groups to be identified.
      All three morphological groups were represented in both the "Occidental" and the
      "Oriental" germplasm, so the correlation between the phenotypic and the genotypic
      data sets was quite weak. The relevance of these results for evolutionary studies
      and the further improvement of eggplant are discussed. The population structure
      of the core set of germplasm shows that it can be used as a basis for an
      association mapping approach. 

PMID- 24040033
TI  - Activation of protein tyrosine phosphatase non-receptor type 2 by spermidine
      exerts anti-inflammatory effects in human THP-1 monocytes and in a mouse model of
      acute colitis.
AB  - BACKGROUND: Spermidine is a dietary polyamine that is able to activate protein
      tyrosine phosphatase non-receptor type 2 (PTPN2). As PTPN2 is known to be a
      negative regulator of interferon-gamma (IFN-gamma)-induced responses, and IFN
      gamma stimulation of immune cells is a critical process in the immunopathology of
      inflammatory bowel disease (IBD), we wished to explore the potential of
      spermidine for reducing pro-inflammatory effects in vitro and in vivo. METHODS:
      Human THP-1 monocytes were treated with IFN-gamma and/or spermidine. Protein
      expression and phosphorylation were analyzed by Western blot, cytokine expression
      by quantitative-PCR, and cytokine secretion by ELISA. Colitis was induced in mice
      by dextran sodium sulfate (DSS) administration. Disease severity was assessed by
      recording body weight, colonoscopy and histology. RESULTS: Spermidine increased
      expression and activity of PTPN2 in THP-1 monocytes and reduced IFN-gamma-induced
      phosphorylation of signal transducer and activator of transcription (STAT) 1 and
      3, as well as p38 mitogen-activated protein kinase (MAPK) in a PTPN2 dependent
      manner. Subsequently, IFN-gamma-induced expression/secretion of intracellular
      cell adhesion molecule (ICAM)-1 mRNA, monocyte chemoattractant protein (MCP)-1,
      and interleukin (IL)-6 was reduced in spermidine-treated cells. The latter
      effects were absent in PTPN2-knockdown cells. In mice with DSS-induced colitis,
      spermidine treatment resulted in ameliorated weight loss and decreased mucosal
      damage indicating reduced disease severity. CONCLUSIONS: Activation of PTPN2 by
      spermidine ameliorates IFN-gamma-induced inflammatory responses in THP-1 cells.
      Furthermore, spermidine treatment significantly reduces disease severity in mice
      with DSS-induced colitis; hence, spermidine supplementation and subsequent PTPN2
      activation may be helpful in the treatment of chronic intestinal inflammation
      such as IBD.

PMID- 24040034
TI  - Statins decrease lung inflammation in mice by upregulating tetraspanin CD9 in
      macrophages.
AB  - Tetraspanins organize protein complexes in tetraspanin-enriched membrane
      microdomains that are distinct from lipid rafts. Our previous studies suggested
      that reduction in the levels of tetraspanins CD9 and CD81 may be involved in the
      progression of inflammatory lung diseases, especially COPD. To search for agents
      that increase the levels of these tetraspanins, we screened 1,165 drugs in
      clinical use and found that statins upregulate CD9 and CD81 in RAW264.7
      macrophages. The lipophilic statins, fluvastatin and simvastatin, reversed LPS
      induced downregulation of CD9 and CD81, simultaneously preventing TNF-alpha and
      matrix metalloproteinase-9 production and spreading of RAW264.7 cells. These
      statins exerted anti-inflammatory effects in vitro in wild-type macrophages but
      not in CD9 knockout macrophages, and decreased lung inflammation in vivo in wild
      type mice but not in CD9 knockout mice, suggesting that their effects are
      dependent on CD9. Mechanistically, the statins promoted reverse transfer of the
      LPS-signaling mediator CD14 from lipid rafts into CD9-enriched microdomains,
      thereby preventing LPS receptor formation. Finally, upregulation of CD9/CD81 by
      statins was related to blockade of GTPase geranylgeranylation in the mevalonate
      pathway. Our data underscore the importance of the negative regulator CD9 in lung
      inflammation, and suggest that statins exert anti-inflammatory effects by
      upregulating tetraspanin CD9 in macrophages. 

PMID- 24040035
TI  - Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung
      cancer.
AB  - Despite optimal radiation therapy (RT), chemotherapy and/or surgery, a majority
      of patients with locally advanced non-small cell lung cancer (NSCLC) fail
      treatment. To identify novel gene targets for improved tumor control, we
      performed whole genome RNAi screens to identify knockdowns that most reproducibly
      increase NSCLC cytotoxicity. These screens identified several proteasome subunits
      among top hits, including the topmost hit PSMA1, a component of the core 20 S
      proteasome. Radiation and proteasome inhibition showed synergistic effects.
      Proteasome inhibition resulted in an 80-90% decrease in homologous recombination
      (HR), a 50% decrease in expression of NF-kappaB-inducible HR genes BRCA1 and
      FANCD2, and a reduction of BRCA1, FANCD2 and RAD51 ionizing radiation-induced
      foci. IkappaBalpha RNAi knockdown rescued NSCLC radioresistance. Irradiation of
      mice with NCI-H460 xenografts after inducible PSMA1 shRNA knockdown markedly
      increased murine survival compared to either treatment alone. Proteasome
      inhibition is a promising strategy for NSCLC radiosensitization via inhibition of
      NF-kappaB-mediated expression of Fanconi Anemia/HR DNA repair genes. 

PMID- 24040036
TI  - Phylogenetic relationships of three Italian merino-derived sheep breeds evaluated
      through a complete mitogenome analysis.
AB  - In Italy, the crisis of the wool industry triggered the necessity to reconvert
      the two traditional Merino-derived breeds, Gentile di Puglia and Sopravissana, to
      meat production, by creating the Merinizzata Italiana. The aim of the present
      study was to assess the genetic diversity of these three Italian Merino-derived
      (IMd) breeds by examining the molecular information encoded in the maternally
      inherited mitochondrial DNA (mtDNA). A parallel molecular investigation was
      performed on the putative paternal and maternal breeds, the Merino from Spain and
      the Appenninica from Italy, respectively, as well as on three unrelated dairy
      breeds (Sarda and Comisana from Italy, and Lacaune from France). Firstly, the
      mtDNA control region of 291 samples was analyzed. When comparing the overall
      genetic distances among the eight stocks, the three IMd breeds clustered together
      close to the Appenninica, thus confirming its parental role. Among the 90 IMd
      samples, 82 different haplotypes were observed, almost all belonging to
      haplogroup B, and only one to A. For 23 mtDNAs, including nine IMd, the analysis
      was then brought to the level of entire mitogenomes. Three distinct sub
      haplogroups within B were found to encompass the IMd samples, with one clade
      (B1a2a1) apparently restricted to those sheep. Thus, despite experiencing a
      drastic reduction in number (mainly due to changes in breeding practices driven
      by the economy), the IMd breeds still represent a reservoir of distinctive
      mitochondrial variants, which could potentially contribute to the development of
      conservation and management programs of Italian sheep breeds. 

PMID- 24040037
TI  - Molecular phylogeny of the Myxobolus and Henneguya genera with several new South
      American species.
AB  - The present study consists of a detailed phylogenetic analysis of myxosporeans of
      the Myxobolus and Henneguya genera, including sequences from 12
      Myxobolus/Henneguya species, parasites of South American pimelodids, bryconids
      and characids. Maximum likelihood and maximum parsimony analyses, based on 18 S
      rDNA gene sequences, showed that the strongest evolutionary signal is the
      phylogenetic affinity of the fish hosts, with clustering mainly occurring
      according to the order and/or family of the host. Of the 12 South American
      species studied here, six are newly described infecting fish from the Brazilian
      Pantanal wetland. Henneguya maculosus n. sp. and Myxobolus flavus n. sp. were
      found infecting both Pseudoplatystoma corruscans and Pseudoplatystoma
      reticulatum; Myxobolus aureus n. sp. and Myxobolus pantanalis n. sp. were
      observed parasitizing Salminus brasiliensis and Myxobolus umidus n. sp. and
      Myxobolus piraputangae n. sp. were detected infecting Brycon hilarii. 

PMID- 24040038
TI  - The diagnostic performance of a single GeneXpert MTB/RIF assay in an intensified
      tuberculosis case finding survey among HIV-infected prisoners in Malaysia.
AB  - BACKGROUND: Delays in tuberculosis (TB) diagnosis, particularly in prisons, is
      associated with detrimental outcomes. The new GeneXpert MTB/RIF assay (Xpert)
      offers accurate and rapid diagnosis of active TB, but its performance in
      improving case detection in high-transmission congregate settings has yet to be
      evaluated. We assessed the diagnostic accuracy of a single Xpert assay in an
      intensified case finding survey among HIV-infected prisoners in Malaysia.
      METHODS: HIV-infected prisoners at a single site provided two early-morning
      sputum specimens to be examined using fluorescence smear microscopy, BACTEC MGIT
      960 liquid culture and a single Xpert. The sensitivity, specificity, negative and
      positive predictive values of Xpert were calculated relative to gold-standard
      results using MGIT 960 liquid culture. Relevant clinical and demographic data
      were used to examine correlates of active TB disease. RESULTS: The majority of
      enrolled subjects with complete data (N=125) were men (90.4%), age <40 years
      (61.6%) and had injected drugs (75.2%). Median CD4 lymphocyte count was 337
      cells/uL (IQR 149-492); only 19 (15.2%) were receiving antiretroviral therapy. Of
      15 culture-positive TB cases, single Xpert assay accurately detected only eight
      previously undiagnosed TB cases, resulting in a sensitivity, specificity,
      positive predictive value and negative predictive value of 53.3% (95% CI 30.12
      75.2%), 100% (95% CI 96.6-100%), 100% (95% CI 67.56-100%) and 94.0% (95% CI 88.2
      97.1%), respectively. Only 1 of 15 (6.7%) active TB cases was smear-positive. The
      prevalence (12%) of undiagnosed active pulmonary TB (15 of 125 prisoners) was
      high and associated with longer duration of drug use (AOR 1.14, 95% CI 1.03-1.26,
      for each year of drug use). CONCLUSIONS: Single Xpert assay improved TB case
      detection and outperformed AFB smear microscopy, but yielded low screening
      sensitivity. Further examination of the impact of HIV infection on the diagnostic
      performance of the new assay alongside other screening methods in correctional
      settings is warranted.

PMID- 24040039
TI  - Role and regulation of the Flp/Tad pilus in the virulence of Pectobacterium
      atrosepticum SCRI1043 and Pectobacterium wasabiae SCC3193.
AB  - In this study, we characterized a putative Flp/Tad pilus-encoding gene cluster,
      and we examined its regulation at the transcriptional level and its role in the
      virulence of potato pathogenic enterobacteria of the genus Pectobacterium. The
      Flp/Tad pilus-encoding gene clusters in Pectobacterium atrosepticum,
      Pectobacterium wasabiae and Pectobacterium aroidearum were compared to previously
      characterized flp/tad gene clusters, including that of the well-studied Flp/Tad
      pilus model organism Aggregatibacter actinomycetemcomitans, in which this pilus
      is a major virulence determinant. Comparative analyses revealed substantial
      protein sequence similarity and open reading frame synteny between the previously
      characterized flp/tad gene clusters and the cluster in Pectobacterium, suggesting
      that the predicted flp/tad gene cluster in Pectobacterium encodes a Flp/Tad pilus
      like structure. We detected genes for a novel two-component system adjacent to
      the flp/tad gene cluster in Pectobacterium, and mutant analysis demonstrated that
      this system has a positive effect on the transcription of selected Flp/Tad pilus
      biogenesis genes, suggesting that this response regulator regulate the flp/tad
      gene cluster. Mutagenesis of either the predicted regulator gene or selected
      Flp/Tad pilus biogenesis genes had a significant impact on the maceration ability
      of the bacterial strains in potato tubers, indicating that the Flp/Tad pilus
      encoding gene cluster represents a novel virulence determinant in Pectobacterium.
      Soft-rot enterobacteria in the genera Pectobacterium and Dickeya are of great
      agricultural importance, and an investigation of the virulence of these pathogens
      could facilitate improvements in agricultural practices, thus benefiting farmers,
      the potato industry and consumers. 

PMID- 24040040
TI  - Bioconversion of alpha-linolenic acid into n-3 long-chain polyunsaturated fatty
      acid in hepatocytes and ad hoc cell culture optimisation.
AB  - This study aimed to establish optimal conditions for a cell culture system that
      would allow the measurement of 18:3n-3 (ALA) bioconversion into n-3 long-chain
      polyunsaturated fatty acid (n-3 LC-PUFA), and to determine the overall pathway
      kinetics. Using rat hepatocytes (FaO) as model cells, it was established that a
      maximum 20:5n-3 (EPA) production from 50 uM ALA initial concentration was
      achieved after 3 days of incubation. Next, it was established that a gradual
      increase in the ALA concentration from 0 up to 125 uM lead to a proportional
      increase in EPA, without concomitant increase in further elongated or desaturated
      products, such as 22:5n-3 (DPA) and 22:6n-3 (DHA) in 3 day incubations. Of
      interest, ALA bioconversion products were observed in the culture medium.
      Therefore, in vitro experiments disregarding the medium fatty acid content are
      underestimating the metabolism efficiency. The novel application of the fatty
      acid mass balance (FAMB) method on cell culture system (cells with medium)
      enabled quantifying the apparent enzymatic activities for the biosynthesis of n-3
      LC-PUFA. The activity of the key enzymes was estimated and showed that, under
      these conditions, 50% (Km) of the theoretical maximal (V max = 3654 umol.g(-1) of
      cell protein.hour(-1)) Fads2 activity on ALA can be achieved with 81 uM initial
      ALA. Interestingly, the apparent activity of Elovl2 (20:5n-3 elongation) was the
      slowest amongst other biosynthesis steps. Therefore, the possible improvement of
      Elovl2 activity is suggested toward a more efficient DHA production from ALA. The
      present study proposed and described an ad hoc optimised cell culture conditions
      and methodology towards achieving a reliable experimental platform, using FAMB,
      to assist in studying the efficiency of ALA bioconversion into n-3 LC-PUFA in
      vitro. The FAMB proved to be a powerful and inexpensive method to generate a
      detailed description of the kinetics of n-3 LC-PUFA biosynthesis enzymes
      activities in vitro.

PMID- 24040041
TI  - Seasonal influenza vaccination coverage rate of target groups in selected cities
      and provinces in China by season (2009/10 to 2011/12).
AB  - BACKGROUND: The objectives of the survey were to identify the level of influenza
      vaccination coverage in China in three influenza seasons 2009/10 to 2011/12, and
      to find out potential predictors for seasonal influenza vaccination. METHODS: In
      September and October 2011, representative urban household telephone surveys were
      conducted in five provinces in China with a response rate of 6%. Four target
      groups were defined for analysis: 1) children <= 5 years old; 2) elderly persons
      aged >= 60 years old; 3) health care workers (persons working in the medical
      field) and 4) chronically ill persons. RESULTS: The overall mean vaccination rate
      was 9.0%. Among the four target groups, the rate of vaccination of children aged
      <= 5 years old (mean = 26%) was highest and the rate of elderly people aged >= 60
      years old (mean = 7.4%) was the lowest, while the rates of persons who suffer
      from a chronic illness (mean = 9.4%) and health care workers (9.5%) were similar.
      A subsidy for influenza vaccination, age group, health care workers, suffering
      from a chronic illness and living in Eastern China were independent significant
      predictors for influenza vaccination. CONCLUSIONS: The seasonal influenza
      vaccination coverage rates among urban populations in selected cities and
      provinces in China were far below previously reported rates in developed
      countries. Influenza vaccination coverage rates differed widely between different
      target groups and provinces in China. Subsidy policy might have a positive effect
      on influenza vaccination rate, but further cost-effectiveness studies, as well as
      the vaccination rate associated factors studies are still needed to inform
      strategies to increase coverage.

PMID- 24040042
TI  - Systematic mutational analysis of the putative hydrolase PqsE: toward a deeper
      molecular understanding of virulence acquisition in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an important opportunistic human pathogen that can
      establish bacterial communication by synchronizing the behavior of individual
      cells in a molecular phenomenon known as "quorum sensing". Through an elusive
      mechanism involving gene products of the pqs operon, the PqsE enzyme is
      absolutely required for the synthesis of extracellular phenazines, including the
      toxic blue pigment pyocyanin, effectively allowing cells to achieve full-fledged
      virulence. Despite several functional and structural attempts at deciphering the
      role of this relevant enzymatic drug target, no molecular function has yet been
      ascribed to PqsE. In the present study, we report a series of alanine scanning
      experiments aimed at altering the biological function of PqsE, allowing us to
      uncover key amino acid positions involved in the molecular function of this
      enzyme. We use sequence analysis and structural overlays with members of
      homologous folds to pinpoint critical positions located in the vicinity of the
      ligand binding cleft and surrounding environment, revealing the importance of a
      unique C-terminal alpha-helical motif in the molecular function of PqsE. Our
      results suggest that the active site of the enzyme involves residues that extend
      further into the hydrophobic core of the protein, advocating for a lid-like
      movement of the two terminal helices. This information should help design virtual
      libraries of PqsE inhibitors, providing means to counter P. aeruginosa virulence
      acquisition and helping to reduce nosocomial infections. 

PMID- 24040043
TI  - Clinical risk factors of death from pneumonia in children with severe acute
      malnutrition in an urban critical care ward of Bangladesh.
AB  - BACKGROUND: Risks of death are high when children with pneumonia also have severe
      acute malnutrition (SAM) as a co-morbidity. However, there is limited published
      information on risk factors of death from pneumonia in SAM children. We evaluated
      clinically identifiable factors associated with death in under-five children who
      were hospitalized for the management of pneumonia and SAM. METHODS: For this
      unmatched case-control design, SAM children of either sex, aged 0-59 months,
      admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease
      Research, Bangladesh (icddr,b) during April 2011 to July 2012 with radiological
      pneumonia were studied. The SAM children with pneumonia who had fatal outcome
      constituted the cases (n = 35), and randomly selected SAM children with pneumonia
      who survived constituted controls (n = 105). RESULTS: The median (inter-quartile
      range) age (months) was comparable among the cases and the controls [8.0 (4.9,
      11.0) vs. 9.7 (5.0, 18.0); p = 0.210)]. In logistic regression analysis, after
      adjusting for potential confounders, such as vomiting, abnormal mental status,
      and systolic hypotension (<70 mm of Hg) in absence of dehydration, fatal cases of
      severely malnourished under-five children with pneumonia were more often
      hypoxemic (OR = 23.15, 95% CI = 4.38-122.42), had clinical dehydration
      (some/severe) (OR = 9.48, 95% CI = 2.42-37.19), abdominal distension at admission
      (OR = 4.41, 95% CI = 1.12-16.52), and received blood transfusion (OR = 5.50, 95%
      CI = 1.21-24.99) for the management of crystalloid resistant systolic
      hypotension. CONCLUSION AND SIGNIFICANCE: We identified hypoxemia, clinical
      dehydration, and abdominal distension as the independent predictors of death in
      SAM children with pneumonia. SAM children with pneumonia who required blood
      transfusion for the management of crystalloid resistant systolic hypotension were
      also at risk for death. Thus, early identification and prompt management of these
      simple clinically recognizable predictors of death and discourage the use of
      blood transfusion for the management of crystalloid resistant systolic
      hypotension may help reduce deaths in such population.

PMID- 24040044
TI  - Identification of a novel fungus, Leptosphaerulina chartarum SJTU59 and
      characterization of its xylanolytic enzymes.
AB  - Xylanolytic enzymes are widely used in processing industries, e.g., pulp and
      paper, food, livestock feeds, and textile. Furthermore, certain xylanotic enzymes
      have demonstrated the capability to improve the resistance and immunity of
      plants. Screening of high-yield microbial xylanolytic enzyme producers is
      significant for improving large-scale cost-effective xylanolytic enzyme
      production. This study provided new evidence of high-level xylanolytic enzyme
      production by a novel fungus, designated Leptosphaerulina chartarum SJTU59. Under
      laboratory conditions, L. chartarum SJTU59 produced xylanolytic enzymes of up to
      17.566 U/mL (i.e., 878.307 U/g substrate). The enzyme solution was relatively
      stable over a wide range of pH (pH 3.0 to pH 9.0) and temperature (40 degrees C
      to 65 degrees C) while showing high resistance to the majority of metal ions
      tested. Composition analysis of the hydrolytic products of xylan showed
      sufficient degradation by xylanolytic enzymes from L. chartarum SJTU59, mainly
      the monosaccharide xylose, and a small amount of xylobiose were enzymatically
      produced; whereas in the presence of sufficient xylan substrates, mainly
      xylooligosaccharides, an emerging prebiotic used in food industry, were produced.
      In addition, the xylanolytic enzyme preparation from L. chartarum SJTU59 could
      initiate tissue necrosis and oxidative burst in tobacco leaves, which may be
      related to enhanced plant defense to adversity and disease. L. chartarum SJTU59
      possessed a complex xylanolytic enzyme system, from which two novel endo-beta-1,4
      xylanases of the glycoside hydrolase (GH) family 10, one novel endo-beta-1,4
      xylanase of the GH family 11, and one novel beta-xylosidase of the GH family 43
      were obtained via rapid amplification of complementary DNA ends. Given the high
      yield and stable properties of xylanolytic enzymes produced by L. chartarum
      SJTU59, future studies will be conducted to characterize the properties of
      individual xylanolytic enzymes from L. chartarum SJTU59. xylanolytic enzymes
      encoding gene(s) of potential use for industrial and agricultural applications
      will be screened to construct genetically engineered strains.

PMID- 24040045
TI  - PSMB9 codon 60 polymorphisms have no impact on the activity of the
      immunoproteasome catalytic subunit B1i expressed in multiple types of solid
      cancer.
AB  - The proteasome is a key regulator of cellular protein homeostasis and is a
      clinically validated anticancer target. The immunoproteasome, a subtype of
      proteasome expressed mainly in hematopoietic cells, was initially recognized for
      its role in antigen presentation during the immune response. Recently, the
      immunoproteasome has been implicated in several disease conditions including
      cancer and autoimmune disorders, but many of the factors contributing to these
      pathological processes remain unknown. In particular, the codon 60 polymorphism
      of the PSMB9 gene encoding the beta1i immunoproteasome catalytic subunit has been
      investigated in the context of a variety of diseases. Despite this, previous
      studies have so far reported inconsistent findings regarding the impact of this
      polymorphism on proteasome activity. Thus, we set out to investigate the impact
      of the PSMB9 codon 60 polymorphism on the expression and activity of the beta1i
      immunoproteasome subunit in a panel of human cancer cell lines. The beta1i
      selective fluorogenic substrate Acetyl-Pro-Ala-Leu-7-amino-4-methylcoumarin was
      used to specifically measure beta1i catalytic activity. Our results indicate that
      the codon 60 Arg/His polymorphism does not significantly alter the expression and
      activity of beta1i among the cell lines tested. Additionally, we also examined
      the expression of beta1i in clinical samples from colon and pancreatic cancer
      patients. Our immunohistochemical analyses showed that ~ 70% of clinical colon
      cancer samples and ~ 53% of pancreatic cancer samples have detectable beta1i
      expression. Taken together, our results indicate that the beta1i subunit of the
      immunoproteasome is frequently expressed in colon and pancreatic cancers but that
      the codon 60 genetic variants of beta1i display similar catalytic activities and
      are unlikely to contribute to the significant inter-cell-line and inter
      individual variabilities in the immunoproteasome activity.

PMID- 24040046
TI  - Defeating crypsis: detection and learning of camouflage strategies.
AB  - Camouflage is perhaps the most widespread defence against predators in nature and
      an active area of interdisciplinary research. Recent work has aimed to understand
      what camouflage types exist (e.g. background matching, disruptive, and
      distractive patterns) and their effectiveness. However, work has almost
      exclusively focused on the efficacy of these strategies in preventing initial
      detection, despite the fact that predators often encounter the same prey
      phenotype repeatedly, affording them opportunities to learn to find those prey
      more effectively. The overall value of a camouflage strategy may, therefore,
      reflect both its ability to prevent detection by predators and resist predator
      learning. We conducted four experiments with humans searching for hidden targets
      of different camouflage types (disruptive, distractive, and background matching
      of various contrast levels) over a series of touch screen trials. As with
      previous work, disruptive coloration was the most successful method of
      concealment overall, especially with relatively high contrast patterns, whereas
      potentially distractive markings were either neutral or costly. However, high
      contrast patterns incurred faster decreases in detection times over trials
      compared to other stimuli. In addition, potentially distractive markings were
      sometimes learnt more slowly than background matching markings, despite being
      found more readily overall. Finally, learning effects were highly dependent upon
      the experimental paradigm, including the number of prey types seen and whether
      subjects encountered targets simultaneously or sequentially. Our results show
      that the survival advantage of camouflage strategies reflects both their ability
      to avoid initial detection (sensory mechanisms) and predator learning (perceptual
      mechanisms). 

PMID- 24040047
TI  - SOX9 duplication linked to intersex in deer.
AB  - A complex network of genes determines sex in mammals. Here, we studied a European
      roe deer with an intersex phenotype that was consistent with a XY genotype with
      incomplete male-determination. Whole genome sequencing and quantitative real-time
      PCR analyses revealed a triple dose of the SOX9 gene, allowing insights into a
      new genetic defect in a wild animal. 

PMID- 24040048
TI  - Genomic phenotyping by barcode sequencing broadly distinguishes between
      alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role
      for aromatic amino acids in cellular recovery after quinone exposure.
AB  - Toxicity screening of compounds provides a means to identify compounds harmful
      for human health and the environment. Here, we further develop the technique of
      genomic phenotyping to improve throughput while maintaining specificity. We
      exposed cells to eight different compounds that rely on different modes of
      action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N
      nitrosourea (MNU), N,N'-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N
      ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione,
      MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl
      carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S.
      cerevisiae 4,852 deletion strains, each identifiable by a unique genetic
      'barcode', were grown in competition; at different time points the ratio between
      the strains was assessed by quantitative high throughput 'barcode' sequencing.
      The method was validated by comparison to previous genomic phenotyping studies
      and 90% of the strains identified as MMS-sensitive here were also identified as
      MMS-sensitive in a much lower throughput solid agar screen. The data provide
      profiles of proteins and pathways needed for recovery after both genotoxic and
      non-genotoxic compounds. In addition, a novel role for aromatic amino acids in
      the recovery after treatment with oxidizing agents was suggested. The role of
      aromatic acids was further validated; the quinone subgroup of oxidizing agents
      were extremely toxic in cells where tryptophan biosynthesis was compromised. 

PMID- 24040050
TI  - Defining quality of life in the children of parents with severe mental illness: a
      preliminary stakeholder-led model.
AB  - Severe parental mental illness poses a challenge to quality of life (QoL) in a
      substantial number of children and adolescents, and improving the lives of these
      children is of urgent political and public health concern. This study used a
      bottom-up qualitative approach to develop a new stakeholder-led model of quality
      of life relevant to this population. Qualitative data were collected from 19
      individuals participating in focus groups or individual interviews. Participants
      comprised 8 clinical academics, health and social care professionals or voluntary
      agency representatives; 5 parents and 6 young people (aged 13-18 yrs) with lived
      experience of severe parental mental illness. Data underwent inductive thematic
      analysis for the purposes of informing a population-specific quality of life
      model. Fifty nine individual themes were identified and grouped into 11 key 'meta
      themes'. Mapping each meta-theme against existing child-centred quality of life
      concepts revealed a multi-dimensional model that endorsed, to a greater or lesser
      degree, the core domains of generic quality of life models. Three new population
      specific priorities were also observed: i) the alleviation of parental mental
      health symptoms, ii) improved problem-based coping skills and iii) increased
      mental health literacy. The identification of these priorities raises questions
      regarding the validity of generic quality of life measures to monitor the
      effectiveness of services for families and children affected by severe mental
      illness. New, age-appropriate instruments that better reflect the life priorities
      and unique challenges faced by the children of parents with severe mental illness
      may need to be developed. Challenges then remain in augmenting and adapting
      service design and delivery mechanisms better to meet these needs. Future child
      and adult mental health services need to work seamlessly alongside statutory
      education and social care services and a growing number of relevant third sector
      providers to address fully the quality of life priorities of these vulnerable
      families. 

PMID- 24040049
TI  - The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid
      receptor activation in cardiomyocytes.
AB  - Aldosterone binds to the mineralocorticoid receptor (MR) and exerts pleiotropic
      effects beyond enhancing renal sodium reabsorption. Excessive mineralocorticoid
      signaling is deleterious during the evolution of cardiac failure, as evidenced by
      the benefits provided by adding MR antagonists (MRA) to standard care in humans.
      In animal models of cardiovascular diseases, MRA reduce cardiac fibrosis.
      Interestingly diuretics such as torasemide also appear efficient to improve
      cardiovascular morbidity and mortality, through several mechanisms. Among them,
      it has been suggested that torasemide could block aldosterone binding to the MR.
      To evaluate whether torasemide acts as a MRA in cardiomyocytes, we compared its
      effects with a classic MRA such as spironolactone. We monitored ligand-induced
      nuclear translocation of MR-GFP and MR transactivation activity in the cardiac
      like cell line H9C2 using a reporter gene assay and known endogenous aldosterone
      regulated cardiac genes. Torasemide did not modify MR nuclear translocation.
      Aldosterone-induced MR transactivation activity was reduced by the MRA
      spironolactone, not by torasemide. Spironolactone blocked the induction by
      aldosterone of endogenous MR-responsive genes (Sgk-1, PAI-1, Orosomucoid-1, Rgs
      2, Serpina-3, Tenascin-X), while torasemide was ineffective. These results show
      that torasemide is not an MR antagonist; its association with MRA in heart
      failure may however be beneficial, through actions on complementary pathways. 

PMID- 24040051
TI  - Cold atmospheric plasma for selectively ablating metastatic breast cancer cells.
AB  - Traditional breast cancer treatments such as surgery and radiotherapy contain
      many inherent limitations with regards to incomplete and nonselective tumor
      ablation. Cold atmospheric plasma (CAP) is an ionized gas where the ion
      temperature is close to room temperature. It contains electrons, charged
      particles, radicals, various excited molecules, UV photons and transient electric
      fields. These various compositional elements have the potential to either enhance
      and promote cellular activity, or disrupt and destroy them. In particular, based
      on this unique composition, CAP could offer a minimally-invasive surgical
      approach allowing for specific cancer cell or tumor tissue removal without
      influencing healthy cells. Thus, the objective of this research is to investigate
      a novel CAP-based therapy for selectively bone metastatic breast cancer
      treatment. For this purpose, human metastatic breast cancer (BrCa) cells and bone
      marrow derived human mesenchymal stem cells (MSCs) were separately treated with
      CAP, and behavioral changes were evaluated after 1, 3, and 5 days of culture.
      With different treatment times, different BrCa and MSC cell responses were
      observed. Our results showed that BrCa cells were more sensitive to these CAP
      treatments than MSCs under plasma dose conditions tested. It demonstrated that
      CAP can selectively ablate metastatic BrCa cells in vitro without damaging
      healthy MSCs at the metastatic bone site. In addition, our study showed that CAP
      treatment can significantly inhibit the migration and invasion of BrCa cells. The
      results suggest the great potential of CAP for breast cancer therapy.

PMID- 24040052
TI  - Variability in the carbon storage of seagrass habitats and its implications for
      global estimates of blue carbon ecosystem service.
AB  - The recent focus on carbon trading has intensified interest in 'Blue Carbon'
      carbon sequestered by coastal vegetated ecosystems, particularly seagrasses. Most
      information on seagrass carbon storage is derived from studies of a single
      species, Posidonia oceanica, from the Mediterranean Sea. We surveyed 17
      Australian seagrass habitats to assess the variability in their sedimentary
      organic carbon (C org) stocks. The habitats encompassed 10 species, in mono
      specific or mixed meadows, depositional to exposed habitats and temperate to
      tropical habitats. There was an 18-fold difference in the Corg stock (1.09-20.14
      mg C org cm(-3) for a temperate Posidonia sinuosa and a temperate, estuarine P.
      australis meadow, respectively). Integrated over the top 25 cm of sediment, this
      equated to an areal stock of 262-4833 g C org m(-2). For some species, there was
      an effect of water depth on the C org stocks, with greater stocks in deeper
      sites; no differences were found among sub-tidal and inter-tidal habitats. The
      estimated carbon storage in Australian seagrass ecosystems, taking into account
      inter-habitat variability, was 155 Mt. At a 2014-15 fixed carbon price of A$25.40
      t(-1) and an estimated market price of $35 t(-1) in 2020, the C org stock in the
      top 25 cm of seagrass habitats has a potential value of $AUD 3.9-5.4 bill. The
      estimates of annual C org accumulation by Australian seagrasses ranged from 0.093
      to 6.15 Mt, with a most probable estimate of 0.93 Mt y(-1) (10.1 t. km(-2) y(
      1)). These estimates, while large, were one-third of those that would be
      calculated if inter-habitat variability in carbon stocks were not taken into
      account. We conclude that there is an urgent need for more information on the
      variability in seagrass carbon stock and accumulation rates, and the factors
      driving this variability, in order to improve global estimates of seagrass Blue
      Carbon storage.

PMID- 24040053
TI  - The newly developed CRF1-receptor antagonists, NGD 98-2 and NGD 9002, suppress
      acute stress-induced stimulation of colonic motor function and visceral
      hypersensitivity in rats.
AB  - Corticotropin releasing factor receptor 1 (CRF1) is the key receptor that
      mediates stress-related body responses. However to date there are no CRF1
      antagonists that have shown clinical efficacy in stress-related diseases. We
      investigated the inhibitory effects of a new generation, topology 2 selective
      CRF1 antagonists, NGD 98-2 and NGD 9002 on exogenous and endogenous CRF-induced
      stimulation of colonic function and visceral hypersensitivity to colorectal
      distension (CRD) in conscious rats. CRF1 antagonists or vehicle were administered
      orogastrically (og) or subcutaneously (sc) before either intracerebroventricular
      (icv) or intraperitoneal (ip) injection of CRF (10 ug/kg), exposure to water
      avoidance stress (WAS, 60 min) or repeated CRD (60 mmHg twice, 10 min on/off at a
      30 min interval). Fecal pellet output (FPO), diarrhea and visceromotor responses
      were monitored. In vehicle (og)-pretreated rats, icv CRF stimulated FPO and
      induced diarrhea in >50% of rats. NGD 98-2 or NGD 9002 (3, 10 and 30 mg/kg, og)
      reduced the CRF-induced FPO response with an inhibitory IC50 of 15.7 and 4.3
      mg/kg respectively. At the highest dose, og NGD 98-2 or NGD 9002 blocked icv CRF
      induced FPO by 67-87% and decreased WAS-induced-FPO by 23-53%. When administered
      sc, NGD 98-2 or NGD 9002 (30 mg/kg) inhibited icv and ip CRF-induced-FPO. The
      antagonists also prevented the development of nociceptive hyper-responsivity to
      repeated CRD. These data demonstrate that topology 2 CRF1 antagonists, NGD 98-2
      and NGD 9002, administered orally, prevented icv CRF-induced colonic secretomotor
      stimulation, reduced acute WAS-induced defecation and blocked the induction of
      visceral sensitization to repeated CRD. 

PMID- 24040054
TI  - Evaluation of the validity of preemptive therapy against cytomegalovirus disease
      based on antigenemia assay with a cutoff of 20 positive cells per two slides.
AB  - BACKGROUND: Preemptive therapy with ganciclovir (GCV) based on the results of a
      cytomegalovirus (CMV) antigenemia assay is a standard strategy for preventing CMV
      disease after allogeneic hematopoietic cell transplantation (HCT). However, the
      appropriate threshold of antigenemia-positive cells for deciding when to start
      GCV remains unclear. PATIENTS: This retrospective study included 80 recipients
      who received HCT from an alternative donor between 2007 and 2011. In 2009, we
      switched the threshold from 3 (3A group, n=24) to 20 (20A group, n=56)
      antigenemia-positive cells per two slides for preemptive therapy after HCT from
      an alternative donor. RESULTS: Early CMV disease within 100 days after HCT was
      observed in one patient in the 20A group. Antiviral agents including GCV, val
      GCV, and foscarnet were given in 17 (71%) and 36 (64%) patients in the 3A and 20A
      groups, respectively (p=0.23). In 13 (23%) patients in the 20A group, the
      initiation of preemptive therapy was avoided because of the change in the cutoff
      value for CMV antigenemia. However, the total dose of GCV was not different
      between the two groups. The use of steroid was significantly associated with CMV
      antigenemia of at least 20 positive cells among patients with low-level
      antigenemia at the first detection. CONCLUSION: The increased threshold up to 20
      positive cells for starting preemptive therapy was not associated with a
      significant increase in CMV disease, but the total dose of GCV was not reduced
      and there was one early CMV disease in the 20A group. We should explore how to
      identify patients who are at high risk for increased antigenemia among patients
      with low-level antigenemia, but at least, preemptive therapy should not be
      withheld in patients who are already receiving systemic steroid.

PMID- 24040055
TI  - An anti-human thymocyte globulin-based reduced-intensity conditioning regimen is
      associated with a higher quality of life and lower organ toxicity without
      affecting lymphocyte reconstitution.
AB  - Reduced-intensity (RIT) conditioning regimens are gaining increased attention as
      a result of their advantages and efficacy. However, no data are available
      regarding whether these regimens improve patient quality of life (QoL). In our
      study, health-related QoL (HRQoL) was retrospectively assessed in 111 patients
      with hematological malignancies. Analysis of the Quality of Life Questionnaire
      indicated that 35 of the RIT patients were able to perform their normal work and
      returned to their baseline levels of function 2 to 3 months after
      transplantation. In the myeloablative (MA) group, only 24 patients were able to
      resume work, and these patients returned to their baseline levels of function 6
      to 8 months after transplantation (68.6% vs. 40.0%, P = 0.004). Grade III-IV
      organ toxicity occurred in 20% of the RIT patients and in 52% of the MA patients
      (P = 0.001), and the cumulative incidences of grades III-IV acute graft-versus
      host disease (GVHD) were 13.7% and 35.0% in RIT and MA patients, respectively (P
      = 0.015). In conclusion, the RIT conditioning regimens were well tolerated by the
      patients, with a low incidence of transplant-related mortality (TRM) and serious
      acute GVHD. In addition, these regimens minimized procedure-related toxicity,
      improved QoL and did not influence lymphocyte reconstitution; however, OS was
      similar for both regimens because the relapse rate was relatively increased in
      the RIT groups.

PMID- 24040056
TI  - Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?
AB  - INTRODUCTION: Temporary occlusion of the hepatoduodenal ligament leads to an
      ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive
      inotropic drug, which induces preconditioning-like adaptive mechanisms due to
      opening of mitochondrial KATP channels. The aim of this study was to examine
      possible protective effects of levosimendan in a rat model of hepatic IR injury.
      MATERIAL AND METHODS: Levosimendan was administered to male Wistar rats 1 hour
      (early pretreatment) or 24 hours (late pretreatment) before induction of 60
      minute segmental liver ischemia. Microcirculation of the liver was monitored by
      laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples
      were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH
      TR) as well as for laboratory tests. Furthermore, liver antioxidant status was
      assessed and HSP72 expression was measured. RESULTS: In both groups pretreated
      with levosimendan, significantly better hepatic microcirculation was observed
      compared to respective IR control groups. Similarly, histological damage was also
      reduced after levosimendan administration. This observation was supported by
      significantly lower activities of serum ALT (p early = 0.02; p late = 0.005), AST
      (p early = 0.02; p late = 0.004) and less DNA damage by TUNEL test (p early =
      0.05; p late = 0.034) and PAR positivity (p early = 0.02; p late = 0.04).
      Levosimendan pretreatment resulted in significant improvement of liver redox
      homeostasis. Further, significantly better mitochondrial function was detected in
      animals receiving late pretreatment. Finally, HSP72 expression was increased by
      IR injury, but it was not affected by levosimendan pretreatment. CONCLUSION:
      Levosimendan pretreatment can be hepatoprotective and it could be useful before
      extensive liver resection.

PMID- 24040057
TI  - Mathematical model for radial expansion and conflation of intratumoral infectious
      centers predicts curative oncolytic virotherapy parameters.
AB  - Simple, inductive mathematical models of oncolytic virotherapy are needed to
      guide protocol design and improve treatment outcomes. Analysis of plasmacytomas
      regressing after a single intravenous dose of oncolytic vesicular stomatitis
      virus in myeloma animal models revealed that intratumoral virus spread was
      spatially constrained, occurring almost exclusively through radial expansion of
      randomly distributed infectious centers. From these experimental observations we
      developed a simple model to calculate the probability of survival for any cell
      within a treated tumor. The model predicted that small changes to the density of
      initially infected cells or to the average maximum radius of infected centers
      would have a major impact on treatment outcome, and this was confirmed
      experimentally. The new model provides a useful and flexible tool for virotherapy
      protocol optimization. 

PMID- 24040058
TI  - Risk factors and their combined effects on the incidence rate of subarachnoid
      hemorrhage--a population-based cohort study.
AB  - BACKGROUND: Prospective studies on the risk factors for subarachnoid hemorrhage
      (SAH) are limited. Moreover, the effect of risk factors on the incidence rates of
      SAH is not well known about. AIMS: In this study, we aimed to identify risk
      factors for SAH and characterize subgroups in a population with a high incidence
      of SAH. METHODS: After recording multiple potential risk factors for SAH at the
      time of enrollment, first ever SAH events between 1972 and 2009 were recorded
      through the nationwide Causes of Death Register and Hospital Discharge Register
      for the population-based cohort of 64 349 participants, who participated in the
      National FINRISK Study between 1972 and 2007 in Finland. RESULTS: During the
      follow-up time of 1.26 million person-years (median 17.9 years, range 0 to 37.9
      years), 437 persons experienced fatal or non-fatal SAH. Crude SAH incidence was
      34.8 (95% confidence interval: 31.7-38.2) per 100 000 person-years among >= 25
      year-old persons. Female sex, high blood pressure values and current smoking were
      confirmed as risk factors for SAH. Previous myocardial infarction, history of
      premature stroke (any kind) in mother and elevated cholesterol levels in men were
      identified as new risk factors for SAH. Depending on the combination of risk
      factors, SAH incidence varied between 8 and 171 per 100 000 person-years.
      CONCLUSIONS: New and previously reported risk factors appear to have a much
      stronger association with the incidence of SAH than is ordinarily seen in
      cardiovascular diseases. Risk factor assessments may facilitate the
      identification of high-risk persons who should be the focus of preventive
      interventions.

PMID- 24040059
TI  - Lack of association between hsa-miR-149 rs2292832 polymorphism and cancer risk: a
      meta-analysis of 12 studies.
AB  - BACKGROUND: MicroRNAs (miRNAs) participate in various cellular processes such as
      cell growth, differentiation, cell death and play an important role in a variety
      of diseases, especially in cancer. Recently, a number of studies have
      investigated the association between single nucleotide polymorphisms (SNPs) on
      the hsa-miR-149 rs2292832 and susceptibility to cancer; however, the results
      remain inconclusive. METHODOLOGY/PRINCIPAL FINDINGS: We carried out a meta
      analysis of 12 studies including 5937 cases and 6081 controls from PubMed to
      assess the association between the hsa-miR-149 rs2292832 and cancer risk by
      pooled odds ratios (ORs) and 95% confidence intervals (CIs). However, our results
      showed that genotype distribution of the hsa-miR-149 rs2292832 was not associated
      with cancer risk in all genetic models. Subgroup analysis by cancer type,
      ethnicity or study design showed no significant association either. CONCLUSION:
      Results of this meta-analysis suggest that the hsa-miR-149 rs2292832 polymorphism
      is not associated with cancer risk in spite of the potentially protective role of
      C allele in hepatocellular carcinoma and male gastric cancer.

PMID- 24040060
TI  - Actin cytoskeleton regulates Hippo signaling.
AB  - Hippo pathway controls the organ size by modulating cell proliferation and
      apoptosis. However, the upstream regulation of hippo signaling by actin
      cytoskeleton is not clear. To elucidate the role of actin as an upstream
      regulator of Hippo signaling, the levels of F (filamentous)-actin in cells were
      elevated using jasplakinolide, an actin-stabilizing drug. Induction of F-actin
      formation in HeLa cells resulted in decreased phosphorylation of YAP, a key
      effector molecule for Hippo signaling. The activated YAP is localized to the cell
      nucleus and YAP increase was associated with increased expression of downstream
      CCN growth factors CCN1/CYR61 and CCN2/CTGF. The effect of the actin-stabilizing
      drug was blocked when YAP levels were suppressed in YAP "knock-down" cells. In
      summary, using an actin-stabilizing drug we show that actin cytoskeleton is one
      of the upstream regulators of Hippo signaling capable of activating YAP and
      increasing its downstream CCN growth factors. 

PMID- 24040061
TI  - Power Doppler ultrasound phenotyping of expanding versus collapsed popliteal
      lymph nodes in murine inflammatory arthritis.
AB  - Rheumatoid arthritis is a chronic inflammatory disease manifested by episodic
      flares in affected joints that are challenging to predict and treat. Longitudinal
      contrast enhanced-MRI (CE-MRI) of inflammatory arthritis in tumor necrosis factor
      transgenic (TNF-Tg) mice has demonstrated that popliteal lymph nodes (PLN)
      increase in volume and contrast enhancement during the pre-arthritic "expanding"
      phase of the disease, and then suddenly "collapse" during knee flare. Given the
      potential of this biomarker of arthritic flare, we aimed to develop a more cost
      effective means of phenotyping PLN using ultrasound (US) imaging. Initially we
      attempted to recapitulate CE-MRI of PLN with subcutaneous footpad injection of US
      microbubbles (DEFINITY(r)). While this approach allowed for phenotyping via
      quantification of lymphatic sinuses in PLN, which showed a dramatic decrease in
      collapsed PLN versus expanding or wild-type (WT) PLN, electron microscopy
      demonstrated that DEFINITY(r) injection also resulted in destruction of the
      lymphatic vessels afferent to the PLN. In contrast, Power Doppler (PD) US is
      innocuous to and efficiently quantifies blood flow within PLN of WT and TNF-Tg
      mice. PD-US demonstrated that expanding PLN have a significantly higher
      normalized PD volume (NPDV) versus collapsed PLN (0.553 +/- 0.007 vs. 0.008 +/-
      0.003; p<0.05). Moreover, we define the upper (>0.030) and lower (<0.016)
      quartile NPDVs in this cohort of mice, which serve as conservative thresholds to
      phenotype PLN as expanding and collapsed, respectively. Interestingly, of the 12
      PLN phenotyped by the two methods, there was disagreement in 4 cases in which
      they were determined to be expanding by CE-MRI and collapsed by PD-US. Since the
      adjacent knee had evidence of synovitis in all 4 cases, we concluded that the PD
      US phenotyping was correct, and that this approach is currently the safest and
      most cost-effective in vivo approach to phenotype murine PLN as a biomarker of
      arthritic flare.

PMID- 24040062
TI  - De novo assembly of the peanut (Arachis hypogaea L.) seed transcriptome revealed
      candidate unigenes for oil accumulation pathways.
AB  - Peanuts are one of the most important edible oil crops in the world. In order to
      survey key genes controlling peanut oil accumulation, we analyzed the seed
      transcriptome in different developmental stages of high- and low-oil peanut
      varieties. About 54 million high quality clean reads were generated, which
      corresponded to 4.85 Gb total nucleotides. These reads were assembled into 59,236
      unique sequences. Differential mRNA processing events were detected for most of
      the peanut Unigenes and found that 15.8% and 18.0% of the Unigenes were
      differentially expressed between high- and low-oil varieties at 30 DAF and 50
      DAF, respectively. Over 1,500 Unigenes involved in lipid metabolism were
      identified, classified, and found to participate in FA synthesis and TAG
      assembly. There were seven possible metabolic pathways involved in the
      accumulation of oil during seed development. This dataset provides more sequence
      resource for peanut plant and will serve as the foundation to understand the
      mechanisms of oil accumulation in oil crops. 

PMID- 24040063
TI  - LPS-induced proNGF synthesis and release in the N9 and BV2 microglial cells: a
      new pathway underling microglial toxicity in neuroinflammation.
AB  - PURPOSE: While aberrant activation of microglial cells was evidently involved in
      neuroinflammation and neurotoxicity in the neurodegenerative diseases such as
      Alzheimer's and Parkinson's disease, objective of study was to address if
      activated microglias deliver their effect by releasing pro-neurotrophins.
      MATERIALS AND METHODS: By in vitro culture of N9 and BV2 cell lines and
      lipopolysaccharide (LPS) stimulation model, generation and release of proNGF,
      proBDNF and MMP-9 was studied in the activated microglial cells by
      immunocytochemistry, western blotting and bioassay methods. RESULTS: Activation
      of microglial cells was observed with obvious increasing iba1-immunoreactivity
      following LPS stimulation in cell culture. Synthesis and up-regulation of proNGF
      protein significantly occurred in N9 and BV2 cells 12h-48h after LPS exposure,
      whereas no significant changes of proBDNF and MMP9 were observed in these
      microglial cell lines with LPS insult. More interestingly, extracellular release
      or secretion of proNGF molecule was also detected in culture medium of N9 cells
      after LPS stimulation. Finally, bioassay using MTT, Hoechst/PI and TUNEL staining
      in SH-SY5Y cells further confirmed that proNGF treatment could result in
      apoptotic cell death but it did not significantly influence cell viability of SH
      SY5Y cells. CONCLUSIONS: This in vitro study revealed LPS-stimulated proNGF
      synthesis and release in activated N9/BV2 microglial cell lines, also suggesting
      that proNGF may appeal a new pathway or possible mechanism underlying microglial
      toxicity in the neuroinflammation and a potential target for therapeutic
      manipulation of the neurodegenerative diseases.

PMID- 24040065
TI  - Prognostic factors in interstitial lung disease associated with primary Sjogren's
      syndrome: a retrospective analysis of 33 pathologically-proven cases.
AB  - INTRODUCTION: Interstitial lung disease associated with primary Sjogren's
      syndrome (pSS-ILD) shows several patterns such as nonspecific interstitial
      pneumonia (NSIP) and usual interstitial pneumonia (UIP). Although UIP is a well
      recognized prognostic determinant in idiopathic interstitial pneumonias, whether
      this is also the case in pSS-ILD is unclear. The objectives of this study were to
      evaluate the prognostic effect of UIP, and to identify the prognostic factors in
      pSS-ILD. METHODS: A retrospective review of medical records identified 33
      consecutive patients with pathologically-proven pSS-ILD. Each patient was
      classified into each ILD pattern by multidisciplinary analysis. Baseline clinical
      radiologic-pathologic characteristics and survival rates were compared between
      the ILD patterns. Finally, the prognostic factors in pSS-ILD were assessed by
      univariate and subsequent multivariate analyses using Cox's proportional hazards
      regression model. RESULTS: pSS-ILD patients were diagnosed with NSIP (n = 22) or
      UIP (n = 11). The median follow-up period was 110 months, and five-year survival
      rate was 87.3% in the total patient population. The prognosis of the UIP patients
      was not significantly different from that of the NSIP patients (NSIP to UIP,
      hazard ratio [HR]: 0.77, 95% confidence interval [CI]: 0.18-3.36, P = 0.73).
      Multivariate analysis identified PaCO2 (HR: 1.68 per 1 Torr increase, 95% CI:
      1.24-2.28, P < 0.01), extent of reticular abnormality on high-resolution CT (HR:
      4.17 per 1-grade increment, 95% CI: 1.18-14.73, P = 0.03), and severity of
      fibroblastic foci (HR: 9.26 per 1-grade increment, 95% CI: 1.74-49.35, P < 0.01)
      as prognostic factors in pSS-ILD. CONCLUSIONS: UIP in pSS-ILD was not related to
      poorer prognosis than NSIP. Assessment of detailed clinical-radiologic-pathologic
      findings is more important than distinguishing UIP to evaluate prognosis in this
      disease.

PMID- 24040064
TI  - Stability of the acetic acid-induced bladder irritation model in alpha chloralose
      anesthetized female cats.
AB  - Time- and vehicle-related variability of bladder and urethral rhabdosphincter
      (URS) activity as well as cardiorespiratory and blood chemistry values were
      examined in the acetic acid-induced bladder irritation model in alpha-chloralose
      anesthetized female cats. Additionally, bladder and urethra were evaluated
      histologically using Mason trichrome and toluidine blue staining. Urodynamic,
      cardiovascular and respiratory parameters were collected during intravesical
      saline infusion followed by acetic acid (0.5%) to irritate the bladder. One hour
      after starting acetic acid infusion, a protocol consisting of a cystometrogram,
      continuous infusion-induced rhythmic voiding contractions, and a 5 min "quiet
      period" (bladder emptied without infusion) was precisely repeated every 30
      minutes. Administration of vehicle (saline i.v.) occurred 15 minutes after
      starting each of the first 7 cystometrograms and duloxetine (1mg/kg i.v.) after
      the 8(th). Acetic acid infusion into the bladder increased URS-EMG activity,
      bladder contraction frequency, and decreased contraction amplitude and capacity,
      compared to saline. Bladder activity and URS activity stabilized within 1 and 2
      hours, respectively. Duloxetine administration significantly decreased bladder
      contraction frequency and increased URS-EMG activity to levels similar to
      previous reports. Cardiorespiratory parameters and blood gas levels remained
      consistent throughout the experiment. The epithelium of the bladder and urethra
      were greatly damaged and edema and infiltration of neutrophils in the lamina
      propria of urethra were observed. These data provide an ample evaluation of the
      health of the animals, stability of voiding function and appropriateness of the
      model for testing drugs designed to evaluate lower urinary tract as well as
      cardiovascular and respiratory systems function. 

PMID- 24040066
TI  - Association studies of MMP-9 in Parkinson's disease and amyotrophic lateral
      sclerosis.
AB  - Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) share several
      clinical and neuropathologic features, and studies suggest that several gene
      mutations and polymorphisms are involved in both conditions. Matrix
      metalloproteinase-9 (MMP-9) is implicated in the pathogenesis of PD and ALS, and
      the C(-1562)T polymorphism in the MMP-9 gene leads to higher promoter activity.
      We therefore investigated whether this polymorphism predisposes to both PD and
      sporadic ALS (sALS). Samples from 351 subjects with PD and 351 healthy controls
      from two major cities in China were compared, while samples from 226 subjects
      with sALS were compared to the same number of controls from three centers in
      China. A possible association between the C(-1562)T polymorphism in the MMP-9
      gene and PD or sALS was assessed by restriction fragment length polymorphism
      (RFLP) analysis. Our results show a significant association between the C(-1562)T
      polymorphism in the MMP-9 gene and risk of PD (odds ratio = 2.268, 95% CI 1.506
      3.416, p<0.001) as well as risk of sALS (odds ratio = 2.163, 95% CI 1.233-3.796,
      p = 0.006), supporting a role for MMP-9 polymorphism in the risk for PD and sALS.

PMID- 24040067
TI  - Inhibition of HIV-1 replication by balsamin, a ribosome inactivating protein of
      Momordica balsamina.
AB  - Ribosome-inactivating proteins (RIPs) are endowed with several medicinal
      properties, including antiviral activity. We demonstrate here that the recently
      identified type I RIP from Momordica balsamina also possesses antiviral activity,
      as determined by viral growth curve assays and single-round infection
      experiments. Importantly, this activity is at play even as doses where the RIP
      has no cytotoxic effect. In addition, balsamin inhibits HIV-1 replication not
      only in T cell lines but also in human primary CD4(+) T cells. This antiviral
      compound exerts its activity at a viral replicative step occurring later than
      reverse-transcription, most likely on viral protein translation, prior to viral
      budding and release. Finally, we demonstrate that balsamin antiviral activity is
      broad since it also impedes influenza virus replication. Altogether our results
      demonstrate that type I RIP can exert a potent anti-HIV-1 activity which paves
      the way for new therapeutic avenues for the treatment of viral infections. 

PMID- 24040068
TI  - HDAC1 and HDAC2 restrain the intestinal inflammatory response by regulating
      intestinal epithelial cell differentiation.
AB  - Acetylation and deacetylation of histones and other proteins depends on histone
      acetyltransferases and histone deacetylases (HDACs) activities, leading to either
      positive or negative gene expression. HDAC inhibitors have uncovered a role for
      HDACs in proliferation, apoptosis and inflammation. However, little is known of
      the roles of specific HDACs in intestinal epithelial cells (IEC). We investigated
      the consequences of ablating both HDAC1 and HDAC2 in murine IECs. Floxed Hdac1
      and Hdac2 homozygous mice were crossed with villin-Cre mice. Mice deficient in
      both IEC HDAC1 and HDAC2 weighed less and survived more than a year. Colon and
      small intestinal sections were stained with hematoxylin and eosin, or with Alcian
      blue and Periodic Acid Schiff for goblet cell identification. Tissue sections
      from mice injected with BrdU for 2 h, 14 h and 48 h were stained with anti-BrdU.
      To determine intestinal permeability, 4-kDa FITC-labeled dextran was given by
      gavage for 3 h. Microarray analysis was performed on total colon RNAs.
      Inflammatory and IEC-specific gene expression was assessed by Western blot or
      semi-quantitative RT-PCR and qPCR with respectively total colon protein and total
      colon RNAs. HDAC1 and HDAC2-deficient mice displayed: 1) increased migration and
      proliferation, with elevated cyclin D1 expression and phosphorylated S6 ribosomal
      protein, a downstream mTOR target; 2) tissue architecture defects with cell
      differentiation alterations, correlating with reduction of secretory Paneth and
      goblet cells in jejunum and goblet cells in colon, increased expression of
      enterocytic markers such as sucrase-isomaltase in the colon, increased expression
      of cleaved Notch1 and augmented intestinal permeability; 3) loss of tissue
      homeostasis, as evidenced by modifications of claudin 3 expression, caspase-3
      cleavage and Stat3 phosphorylation; 4) chronic inflammation, as determined by
      inflammatory molecular expression signatures and altered inflammatory gene
      expression. Thus, epithelial HDAC1 and HDAC2 restrain the intestinal inflammatory
      response, by regulating intestinal epithelial cell proliferation and
      differentiation. 

PMID- 24040069
TI  - Cell-specific post-transcriptional regulation of gamma-synuclein gene by micro
      RNAs.
AB  - gamma-Synuclein is a member of the synucleins family of small proteins, which
      consists of three members:alpha, beta- and gamma-synuclein. gamma-Synuclein is
      abnormally expressed in a high percentage of advanced and metastatic tumors, but
      not in normal or benign tissues. Furthermore, gamma-synuclein expression is
      strongly correlated with disease progression, and can stimulate proliferation,
      induce invasion and metastasis of cancer cells. gamma-Synuclein transcription is
      regulated basically through the binding of AP-1 to specific sequences in intron
      1. Here we show that gamma-synuclein expression may be also regulated by micro
      RNAs (miRs) on post-transcriptional level. According to prediction by several
      methods, the 3'-untranslated region (UTR) of gamma-synuclein gene contains
      targets for miRs. Insertion of gamma-synuclein 3'-UTR downstream of the reporter
      luciferase (LUC) gene causes a 51% reduction of LUC activity after transfection
      into SKBR3 and Y79 cells, confirming the presence of efficient targets for miRs
      in this fragment. Expression of miR-4437 and miR-4674 for which putative targets
      in 3'-UTR were predicted caused a 61.2% and 60.1% reduction of endogenous gamma
      synuclein expression confirming their role in gene expression regulation. On the
      other hand, in cells overexpressing gamma-synuclein no significant effect of miRs
      on gamma-synuclein expression was found suggesting that miRs exert their
      regulatory effect only at low or moderate, but not at high level of gamma
      synuclein expression. Elevated level of gamma-synuclein differentially changes
      the level of several miRs expression, upregulating the level of some miRs and
      downregulating the level of others. Three miRs upregulated as a result of gamma
      synuclein overexpression, i.e., miR-885-3p, miR-138 and miR-497 have putative
      targets in 3'-UTR of the gamma-synuclein gene. Some of miRs differentially
      regulated by gamma-synuclein may modulate signaling pathways and cancer related
      gene expression. This study demonstrates that miRs might provide cell-specific
      regulation of gamma-synuclein expression and set the stage to further evaluate
      their role in pathophysiological processes. 

PMID- 24040070
TI  - Phosphorylation of the Drosophila transient receptor potential ion channel is
      regulated by the phototransduction cascade and involves several protein kinases
      and phosphatases.
AB  - Protein phosphorylation plays a cardinal role in regulating cellular processes in
      eukaryotes. Phosphorylation of proteins is controlled by protein kinases and
      phosphatases. We previously reported the light-dependent phosphorylation of the
      Drosophila transient receptor potential (TRP) ion channel at multiple sites. TRP
      generates the receptor potential upon stimulation of the photoreceptor cell by
      light. An eye-enriched protein kinase C (eye-PKC) has been implicated in the
      phosphorylation of TRP by in vitro studies. Other kinases and phosphatases of TRP
      are elusive. Using phosphospecific antibodies and mass spectrometry, we here show
      that phosphorylation of most TRP sites depends on the phototransduction cascade
      and the activity of the TRP ion channel. A candidate screen to identify kinases
      and phosphatases provided in vivo evidence for an involvement of eye-PKC as well
      as other kinases and phosphatases in TRP phosphorylation. 

PMID- 24040071
TI  - Fate analysis of adult hippocampal progenitors in a murine model of fetal alcohol
      spectrum disorder (FASD).
AB  - Prenatal alcohol exposure can lead to fetal alcohol spectrum disorder (FASD) and
      associated behavioral impairments that may be linked to disruptions in adult
      hippocampal neurogenesis. Social and physical enrichment has been proposed as a
      potential therapeutic approach toward reversing behavioral deficits associated
      with FASD and is also a potent stimulator of adult hippocampal neurogenesis. In
      the present study, we utilized a genetic fate mapping approach in nestin
      CreER(T2)/YFP bitransgenic mice to identify the stage-specific impact of prenatal
      alcohol exposure on the stepwise maturation of adult hippocampal progenitors.
      Using a limited alcohol access "drinking-in-the-dark" model of FASD, we confirm
      previous findings that moderate prenatal alcohol exposure has no effect on adult
      neurogenesis under standard housing conditions, but abolishes the neurogenic
      response to enriched environment (EE). Furthermore, we demonstrate that this
      effect is primarily due to failed EE-mediated survival of postmitotic neurons.
      Finally, we demonstrate that the neurogenic deficit is associated with impaired
      spatial pattern recognition, as demonstrated by delayed learning of FASD-EE mice
      in an A-B contextual discrimination task. These results identify a potential
      maturational stage-specific mechanism(s) underlying impaired neurogenic function
      in a preclinical model of FASD, and provide a basis for testing regulatory
      pathways in this model through conditional and inducible manipulation of gene
      expression in the adult hippocampal progenitor population. 

PMID- 24040072
TI  - The dorsolateral prefrontal cortex plays a role in self-initiated elaborative
      cognitive processing during episodic memory encoding: rTMS evidence.
AB  - During episodic memory encoding, elaborative cognitive processing can improve
      later recall or recognition. While multiple studies examined the neural
      correlates of encoding strategies, few studies have explicitly focused on the
      self-initiation of elaborative encoding. Repetitive transcranial magnetic
      stimulation (rTMS), a method which can transiently disrupt neural activity, was
      administered during an associative encoding task. rTMS was either applied to the
      left dorsolateral prefrontal cortex (DLPFC) or to the vertex (a control region
      not involved in memory encoding) during presentation of pairs of words. Pairs
      could be semantically related or not related. Two encoding instructions were
      given, either cueing participants to analyze semantic relationships (cued
      condition), or to memorize the pair without any specific strategy cues (the self
      initiated condition). Participants filled out a questionnaire regarding their use
      of memory strategies and performed a cued-recall task. We hypothesized that if
      the DLPFC plays a role in the self-initiation of elaborative encoding we would
      observe a reduction in memory performance in the self-initiated condition,
      particularly for related. We found a significant correlation between the effects
      of rTMS and strategy use, only in the self-initiated condition with related
      pairs. High strategy users showed reduced performance following DLPFC
      stimulation, while low strategy users tended to show increased recall following
      DLPFC stimulation during encoding. These results suggest the left DLPFC may be
      involved in the self-initiation of memory strategy use, and individuals may
      utilize different neural networks depending on their use of encoding strategies. 

PMID- 24040074
TI  - Baseline monitoring of the western Arctic Ocean estimates 20% of Canadian basin
      surface waters are undersaturated with respect to aragonite.
AB  - Marine surface waters are being acidified due to uptake of anthropogenic carbon
      dioxide, resulting in surface ocean areas of undersaturation with respect to
      carbonate minerals, including aragonite. In the Arctic Ocean, acidification is
      expected to occur at an accelerated rate with respect to the global oceans, but a
      paucity of baseline data has limited our understanding of the extent of Arctic
      undersaturation and of regional variations in rates and causes. The lack of data
      has also hindered refinement of models aimed at projecting future trends of ocean
      acidification. Here, based on more than 34,000 data records collected in 2010 and
      2011, we establish a baseline of inorganic carbon data (pH, total alkalinity,
      dissolved inorganic carbon, partial pressure of carbon dioxide, and aragonite
      saturation index) for the western Arctic Ocean. This data set documents aragonite
      undersaturation in ~ 20% of the surface waters of the combined Canada and Makarov
      basins, an area characterized by recent acceleration of sea ice loss.
      Conservative tracer studies using stable oxygen isotopic data from 307 sites show
      that while the entire surface of this area receives abundant freshwater from
      meteoric sources, freshwater from sea ice melt is most closely linked to the
      areas of carbonate mineral undersaturation. These data link the Arctic Ocean's
      largest area of aragonite undersaturation to sea ice melt and atmospheric CO2
      absorption in areas of low buffering capacity. Some relatively supersaturated
      areas can be linked to localized biological activity. Collectively, these
      observations can be used to project trends of ocean acidification in higher
      latitude marine surface waters where inorganic carbon chemistry is largely
      influenced by sea ice meltwater.

PMID- 24040073
TI  - SNP (-617C>A) in ARE-like loci of the NRF2 gene: a new biomarker for prognosis of
      lung adenocarcinoma in Japanese non-smoking women.
AB  - PURPOSE: The transcription factor NRF2 plays a pivotal role in protecting normal
      cells from external toxic challenges and oxidative stress, whereas it can also
      endow cancer cells resistance to anticancer drugs. At present little information
      is available about the genetic polymorphisms of the NRF2 gene and their clinical
      relevance. We aimed to investigate the single nucleotide polymorphisms in the
      NRF2 gene as a prognostic biomarker in lung cancer. EXPERIMENTAL DESIGN: We
      prepared genomic DNA samples from 387 Japanese patients with primary lung cancer
      and detected SNP (c.-617C>A; rs6721961) in the ARE-like loci of the human NRF2
      gene by the rapid genetic testing method we developed in this study. We then
      analyzed the association between the SNP in the NRF2 gene and patients' overall
      survival. RESULTS: Patients harboring wild-type (WT) homozygous (c.-617C/C), SNP
      heterozygous (c.-617C/A), and SNP homozygous (c.-617A/A) alleles numbered 216
      (55.8%), 147 (38.0%), and 24 (6.2%), respectively. Multivariate logistic
      regression models revealed that SNP homozygote (c.-617A/A) was significantly
      related to gender. Its frequency was four-fold higher in female patients than in
      males (10.8% female vs 2.7% male) and was associated with female non-smokers with
      adenocarcinoma. Interestingly, lung cancer patients carrying NRF2 SNP homozygous
      alleles (c.-617A/A) and the 309T (WT) allele in the MDM2 gene exhibited
      remarkable survival over 1,700 days after surgical operation (log-rank p =
      0.021). CONCLUSION: SNP homozygous (c.-617A/A) alleles in the NRF2 gene are
      associated with female non-smokers with adenocarcinoma and regarded as a
      prognostic biomarker for assessing overall survival of patients with lung
      adenocarcinoma.

PMID- 24040075
TI  - Lost in translation: assessing effectiveness of focus group questioning
      techniques to develop improved translation of terminology used in HIV prevention
      clinical trials.
AB  - INTRODUCTION: Achieving participant comprehension has proven to be one of the
      most difficult, practical, and ethical challenges of HIV prevention clinical
      trials. It becomes even more challenging when local languages do not have
      equivalent scientific and technical vocabularies, rendering communication of
      scientific concepts in translated documents extremely difficult. Even when
      bilingual lexicons are developed, there is no guarantee that participants
      understand the terminology as translated. METHODS: We conducted twelve focus
      groups with women of reproductive age in Mwanza, Tanzania to explore the
      effectiveness of four questioning techniques for: (1) assessing participants'
      familiarity with existing technical terms and concepts, (2) generating a list of
      acceptable technical and non-technical terms, (3) testing our definitions of
      technical terms, and (4) verifying participants' preferences for terms. Focus
      groups were transcribed, translated, and qualitatively analyzed. RESULTS AND
      DISCUSSION: A translation process that uses all four questioning techniques in a
      step-wise approach is an effective way to establish a baseline understanding of
      participants' familiarity with research terms, to develop and test translatable
      definitions, and to identify participants' preferred terminology for
      international HIV clinical research. This may help to ensure that important
      concepts are not "lost in translation." The results emphasize the importance of
      using a variety of techniques depending on the level of participant familiarity
      with research concepts, the existence of colloquial or technical terms in the
      target language, and the inherent complexity of the terms.

PMID- 24040076
TI  - Phylogeny drives large scale patterns in Australian marine bioactivity and
      provides a new chemical ecology rationale for future biodiscovery.
AB  - Twenty-five years of Australian marine bioresources collecting and research by
      the Australian Institute of Marine Science (AIMS) has explored the breadth of
      latitudinally and longitudinally diverse marine habitats that comprise
      Australia's ocean territory. The resulting AIMS Bioresources Library and
      associated relational database integrate biodiversity with bioactivity data, and
      these resources were mined to retrospectively assess biogeographic, taxonomic and
      phylogenetic patterns in cytotoxic, antimicrobial, and central nervous system
      (CNS)-protective bioactivity. While the bioassays used were originally chosen to
      be indicative of pharmaceutically relevant bioactivity, the results have
      qualified ecological relevance regarding secondary metabolism. In general,
      metazoan phyla along the deuterostome phylogenetic pathway (eg to Chordata) and
      their ancestors (eg Porifera and Cnidaria) had higher percentages of bioactive
      samples in the assays examined. While taxonomy at the phylum level and higher
      order phylogeny groupings helped account for observed trends, taxonomy to genus
      did not resolve the trends any further. In addition, the results did not identify
      any biogeographic bioactivity hotspots that correlated with biodiversity
      hotspots. We conclude with a hypothesis that high-level phylogeny, and therefore
      the metabolic machinery available to an organism, is a major determinant of
      bioactivity, while habitat diversity and ecological circumstance are possible
      drivers in the activation of this machinery and bioactive secondary metabolism.
      This study supports the strategy of targeting phyla from the deuterostome lineage
      (including ancestral phyla) from biodiverse marine habitats and ecological
      niches, in future biodiscovery, at least that which is focused on vertebrate
      (including human) health. 

PMID- 24040077
TI  - Meal frequencies modify the effect of common genetic variants on body mass index
      in adolescents of the northern Finland birth cohort 1986.
AB  - Recent studies suggest that meal frequencies influence the risk of obesity in
      children and adolescents. It has also been shown that multiple genetic loci
      predispose to obesity already in youth. However, it is unknown whether meal
      frequencies could modulate the association between single nucleotide
      polymorphisms (SNPs) and the risk of obesity. We examined the effect of two meal
      patterns on weekdays -5 meals including breakfast (regular) and <= 4 meals with
      or without breakfast (meal skipping) - on the genetic susceptibility to increased
      body mass index (BMI) in Finnish adolescents. Eight variants representing 8 early
      life obesity-susceptibility loci, including FTO and MC4R, were genotyped in 2215
      boys and 2449 girls aged 16 years from the population-based Northern Finland
      Birth Cohort 1986. A genetic risk score (GRS) was calculated for each individual
      by summing the number of BMI-increasing alleles across the 8 loci. Weight and
      height were measured and dietary data were collected using self-administered
      questionnaires. Among meal skippers, the difference in BMI between high-GRS and
      low-GRS (<8 and >= 8 BMI-increasing alleles) groups was 0.90 (95% CI 0.63,1.17)
      kg/m(2), whereas in regular eaters, this difference was 0.32 (95% CI 0.06,0.57)
      kg/m(2) (p interaction = 0.003). The effect of each MC4R rs17782313 risk allele
      on BMI in meal skippers (0.47 [95% CI 0.22,0.73] kg/m(2)) was nearly three-fold
      compared with regular eaters (0.18 [95% CI -0.06,0.41] kg/m(2)) (p interaction =
      0.016). Further, the per-allele effect of the FTO rs1421085 was 0.24 (95% CI
      0.05,0.42) kg/m(2) in regular eaters and 0.46 (95% CI 0.27,0.66) kg/m(2) in meal
      skippers but the interaction between FTO genotype and meal frequencies on BMI was
      significant only in boys (p interaction = 0.015). In summary, the regular five
      meal pattern attenuated the increasing effect of common SNPs on BMI in
      adolescents. Considering the epidemic of obesity in youth, the promotion of
      regular eating may have substantial public health implications.

PMID- 24040078
TI  - MiR-130b is a prognostic marker and inhibits cell proliferation and invasion in
      pancreatic cancer through targeting STAT3.
AB  - Accumulating evidence indicates that microRNAs (miRNAs) are aberrantly expressed
      in human cancer and contribute to the tumorigenesis, but their roles in
      pancreatic cancer are still largely unknown. In this study, our data showed that
      miR-130b was significantly downregulated in 52 pairs of pancreatic cancer tissues
      and five cell lines. Furthermore, the deregulated miR-130b was correlated with
      worse prognosis, increased tumor size, late TNM stage, lymphatic invasion and
      distant metastasis. Multivariate analysis showed that miR-130b expression was a
      significant and independent prognostic predictor for pancreatic cancer patients.
      Functional studies indicated that the overexpression of miR-130b dramatically
      suppressed the proliferation of pancreatic cancer cells both in vitro and in
      vivo, which could be attributed to the induction of apoptosis and cell cycle
      arrest at S phase. Meanwhile, an overexpressed miR-130b remarkably inhibited the
      invasive ability of pancreatic cancer cells. Moreover, the dual luciferase assay
      revealed that STAT3 was directly targeted by miR-130b, which was further
      confirmed by the inverse expression of miR-130b and STAT3 in pancreatic cancer
      samples. Our findings suggested that miR-130b might have a considerable potential
      in prognosis identification and application of therapy for pancreatic cancer. 

PMID- 24040079
TI  - Nature-inspired antimicrobial polymers--assessment of their potential for
      biomedical applications.
AB  - We explored the potential of poly(oxonorbornene)-based synthetic mimics of
      antimicrobial peptides (SMAMPs), a promising new class of antimicrobial polymers
      with cell-selectivity and low resistance development potential, for clinical
      applications. We evaluated their antimicrobial activity against a panel of seven
      clinical and regulatory relevant bacteria strains, and tested their toxicity with
      two different kinds of primary human cells. For the antimicrobial activity, we
      performed the minimum inhibitory concentration (MIC) assay and determined the
      minimum bactericidal concentration (MBC) according to the NCCLS guidelines. The
      results revealed specific problems that may occur when testing the antimicrobial
      activity of amphiphilic cationic polymers, and confirmed the working hypothesis
      that the more hydrophilic SMAMP polymers in our portfolio were 'doubly
      selective', i.e. they are not only selective for bacteria over mammalian cells,
      but also for Gram-positive over Gram-negative bacteria. The data also showed that
      we could improve the broad-band activity of one SMAMP, and in combination with
      the results from the cell toxicity experiments, identified this polymer as a
      promising candidate for further in-vitro and in-vivo testing. Transmission
      electron studies revealed that the cellular envelopes of both E. coli and S.
      aureus were severely damaged due to SMAMP action on the bacterial membrane, which
      strengthened the argument that SMAMPs closely resemble antimicrobial peptides. To
      test cell toxicity, we used the traditional hemolysis assay with human red blood
      cells, and the novel xCelligence assay with primary human fibroblasts. The data
      reported here is the first example in which a hemolysis assay is benchmarked
      against the xCelligence assay. It revealed that the same trends were obtained
      using these complementary methods. This establishes the xCelligence assay with
      primary human cells as a useful tool for SMAMP characterization. 

PMID- 24040080
TI  - Time- and task-dependent non-neural effects of real and sham TMS.
AB  - Transcranial magnetic stimulation (TMS) is widely used in experimental brain
      research to manipulate brain activity in humans. Next to the intended neural
      effects, every TMS pulse produces a distinct clicking sound and sensation on the
      head which can also influence task performance. This necessitates careful
      consideration of control conditions in order to ensure that behavioral effects of
      interest can be attributed to the neural consequences of TMS and not to non
      neural effects of a TMS pulse. Surprisingly, even though these non-neural effects
      of TMS are largely unknown, they are often assumed to be unspecific, i.e. not
      dependent on TMS parameters. This assumption is inherent to many control
      strategies in TMS research but has recently been challenged on empirical grounds.
      Here, we further develop the empirical basis of control strategies in TMS
      research. We investigated the time-dependence and task-dependence of the non
      neural effects of TMS and compared real and sham TMS over vertex. Critically, we
      show that non-neural TMS effects depend on a complex interplay of these factors.
      Although TMS had no direct neural effects, both pre- and post-stimulus TMS time
      windows modulated task performance on both a sensory detection task and a
      cognitive angle judgment task. For the most part, these effects were
      quantitatively similar across tasks but effect sizes were clearly different.
      Moreover, the effects of real and sham TMS were almost identical with interesting
      exceptions that shed light on the relative contribution of auditory and somato
      sensory aspects of a TMS pulse. Knowledge of such effects is of critical
      importance for the interpretation of TMS experiments and helps deciding what
      constitutes an appropriate control condition. Our results broaden the empirical
      basis of control strategies in TMS research and point at potential pitfalls that
      should be avoided. 

PMID- 24040081
TI  - Combination of alpha-melanocyte stimulating hormone with conventional antibiotics
      against methicillin resistant Staphylococcus aureus.
AB  - Our previous studies revealed that alpha-melanocyte stimulating hormone (alpha
      MSH) is strongly active against Staphylococcus aureus (S. aureus) including
      methicillin resistant S. aureus (MRSA). Killing due to alpha-MSH occurred by
      perturbation of the bacterial membrane. In the present study, we investigated the
      in vitro synergistic potential of alpha-MSH with five selected conventional
      antibiotics viz., oxacillin (OX), ciprofloxacin (CF), tetracycline (TC),
      gentamicin (GM) and rifampicin (RF) against a clinical MRSA strain which carried
      a type III staphylococcal cassette chromosome mec (SCCmec) element and belonged
      to the sequence type (ST) 239. The strain was found to be highly resistant to OX
      (minimum inhibitory concentration (MIC) = 1024 ug/ml) as well as to other
      selected antimicrobial agents including alpha-MSH. The possibility of the
      existence of intracellular target sites of alpha-MSH was evaluated by examining
      the DNA, RNA and protein synthesis pathways. We observed a synergistic potential
      of alpha-MSH with GM, CF and TC. Remarkably, the supplementation of alpha-MSH
      with GM, CF and TC resulted in >= 64-, 8- and 4-fold reductions in their minimum
      bactericidal concentrations (MBCs), respectively. Apart from membrane
      perturbation, in this study we found that alpha-MSH inhibited ~ 53% and ~ 47% DNA
      and protein synthesis, respectively, but not RNA synthesis. Thus, the mechanistic
      analogy between alpha-MSH and CF or GM or TC appears to be the reason for the
      observed synergy between them. In contrast, alpha-MSH did not act synergistically
      with RF which may be due to its inability to inhibit RNA synthesis (<10%).
      Nevertheless, the combination of alpha-MSH with RF and OX showed an enhanced
      killing by ~ 45% and ~ 70%, respectively, perhaps due to the membrane disrupting
      properties of alpha-MSH. The synergistic activity of alpha-MSH with antibiotics
      is encouraging, and promises to restore the lost potency of discarded
      antibiotics.

PMID- 24040082
TI  - Calcium sensing receptor expression in ovine amniotic fluid mesenchymal stem
      cells and the potential role of R-568 during osteogenic differentiation.
AB  - Amniotic fluid-derived stem (AFS) cells have been identified as a promising
      source for cell therapy applications in bone traumatic and degenerative damage.
      Calcium Sensing Receptor (CaSR), a G protein-coupled receptor able to bind
      calcium ions, plays a physiological role in regulating bone metabolism. It is
      expressed in different kinds of cells, as well as in some stem cells. The bone
      CaSR could potentially be targeted by allosteric modulators, in particular by
      agonists such as calcimimetic R-568, which may potentially be helpful for the
      treatment of bone disease. The aim of our study was first to investigate the
      presence of CaSR in ovine Amniotic Fluid Mesenchymal Stem Cells (oAFMSCs) and
      then the potential role of calcimimetics in in vitro osteogenesis. oAFMSCs were
      isolated, characterized and analyzed to examine the possible presence of CaSR by
      western blotting and flow cytometry analysis. Once we had demonstrated CaSR
      expression, we worked out that 1 uM R-568 was the optimal and effective
      concentration by cell viability test (MTT), cell number, Alkaline Phosphatase
      (ALP) and Alizarin Red S (ARS) assays. Interestingly, we observed that basal
      diffuse CaSR expression in oAFMSCs increased at the membrane when cells were
      treated with R-568 (1 uM), potentially resulting in activation of the receptor.
      This was associated with significantly increased cell mineralization (ALP and ARS
      staining) and augmented intracellular calcium and Inositol trisphosphate (IP3)
      levels, thus demonstrating a potential role for calcimimetics during osteogenic
      differentiation. Calhex-231, a CaSR allosteric inhibitor, totally reversed R-568
      induced mineralization. Taken together, our results demonstrate for the first
      time that CaSR is expressed in oAFMSCs and that calcimimetic R-568, possibly
      through CaSR activation, can significantly improve the osteogenic process. Hence,
      our study may provide useful information on the mechanisms regulating
      osteogenesis in oAFMSCs, perhaps prompting the use of calcimimetics in bone
      regenerative medicine.

PMID- 24040083
TI  - Wild type p53 transcriptionally represses the SALL2 transcription factor under
      genotoxic stress.
AB  - SALL2- a member of the Spalt gene family- is a poorly characterized transcription
      factor found deregulated in various cancers, which suggests it plays a role in
      the disease. We previously identified SALL2 as a novel interacting protein of
      neurotrophin receptors and showed that it plays a role in neuronal function,
      which does not necessarily explain why or how SALL2 is deregulated in cancer.
      Previous evidences indicate that SALL2 gene is regulated by the WT1 and AP4
      transcription factors. Here, we identified SALL2 as a novel downstream target of
      the p53 tumor suppressor protein. Bioinformatic analysis of the SALL2 gene
      revealed several putative p53 half sites along the promoter region. Either
      overexpression of wild-type p53 or induction of the endogenous p53 by the
      genotoxic agent doxorubicin repressed SALL2 promoter activity in various cell
      lines. However R175H, R249S, and R248W p53 mutants, frequently found in the
      tumors of cancer patients, were unable to repress SALL2 promoter activity,
      suggesting that p53 specific binding to DNA is important for the regulation of
      SALL2. Electrophoretic mobility shift assay demonstrated binding of p53 to one of
      the identified p53 half sites in the Sall2 promoter, and chromatin
      immunoprecipitation analysis confirmed in vivo interaction of p53 with the
      promoter region of Sall2 containing this half site. Importantly, by using a p53ER
      (TAM) knockin model expressing a variant of p53 that is completely dependent on 4
      hydroxy-tamoxifen for its activity, we show that p53 activation diminished SALL2
      RNA and protein levels during genotoxic cellular stress in primary mouse embryo
      fibroblasts (MEFs) and radiosensitive tissues in vivo. Thus, our finding
      indicates that p53 represses SALL2 expression in a context-specific manner,
      adding knowledge to the understanding of SALL2 gene regulation, and to a
      potential mechanism for its deregulation in cancer. 

PMID- 24040084
TI  - Innate and introduced resistance traits in genetically modified aspen trees and
      their effect on leaf beetle feeding.
AB  - Genetic modifications of trees may provide many benefits, e.g. increase
      production, and mitigate climate change and herbivore impacts on forests.
      However, genetic modifications sometimes result in unintended effects on innate
      traits involved in plant-herbivore interactions. The importance of intentional
      changes in plant defence relative to unintentional changes and the natural
      variation among clones used in forestry has not been evaluated. By a combination
      of biochemical measurements and bioassays we investigated if insect feeding on GM
      aspens is more affected by intentional (induction Bt toxins) than of
      unintentional, non-target changes or clonal differences in innate plant defence.
      We used two hybrid wildtype clones (Populus tremula x P. tremuloides and Populus
      tremula x P. alba) of aspen that have been genetically modified for 1) insect
      resistance (two Bt lines) or 2) reduced lignin properties (two lines COMT and
      CAD), respectively. Our measurements of biochemical properties suggest that
      unintended changes by GM modifications (occurring due to events in the
      transformation process) in innate plant defence (phenolic compounds) were
      generally smaller but fundamentally different than differences seen among
      different wildtype clones (e.g. quantitative and qualitative, respectively).
      However, neither clonal differences between the two wildtype clones nor
      unintended changes in phytochemistry influenced consumption by the leaf beetle
      (Phratora vitellinae). By contrast, Bt induction had a strong direct intended
      effect as well as a post experiment effect on leaf beetle consumption. The latter
      suggested lasting reduction of beetle fitness following Bt exposure that is
      likely due to intestinal damage suffered by the initial Bt exposure. We conclude
      that Bt induction clearly have intended effects on a target species. Furthermore,
      the effect of unintended changes in innate plant defence traits, when they occur,
      are context dependent and have in comparison to Bt induction probably less
      pronounced effect on targeted herbivores. 

PMID- 24040085
TI  - Projected impact of a sodium consumption reduction initiative in Argentina: an
      analysis from the CVD policy model--Argentina.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in adults
      in Argentina. Sodium reduction policies targeting processed foods were
      implemented in 2011 in Argentina, but the impact has not been evaluated. The aims
      of this study are to use Argentina-specific data on sodium excretion and project
      the impact of Argentina's sodium reduction policies under two scenarios - the 2
      year intervention currently being undertaken or a more persistent 10 year sodium
      reduction strategy. METHODS: We used Argentina-specific data on sodium excretion
      by sex and projected the impact of the current strategy on sodium consumption and
      blood pressure decrease. We assessed the projected impact of sodium reduction
      policies on CVD using the Cardiovascular Disease (CVD) Policy Model, adapted to
      Argentina, modeling two alternative policy scenarios over the next decade.
      RESULTS: Our study finds that the initiative to reduce sodium consumption
      currently in place in Argentina will have substantial impact on CVD over the next
      10 years. Under the current proposed policy of 2-year sodium reduction, the mean
      sodium consumption is projected to decrease by 319-387 mg/day. This decrease is
      expected to translate into an absolute reduction of systolic blood pressure from
      0.93 mmHg to 1.81 mmHg. This would avert about 19,000 all-cause mortality, 13,000
      total myocardial infarctions, and 10,000 total strokes over the next decade. A
      more persistent sodium reduction strategy would yield even greater CVD benefits.
      CONCLUSION: The impact of the Argentinean initiative would be effective in
      substantially reducing mortality and morbidity from CVD. This paper provides
      evidence-based support to continue implementing strategies to reduce sodium
      consumption at a population level.

PMID- 24040086
TI  - Previous exposure to an RNA virus does not protect against subsequent infection
      in Drosophila melanogaster.
AB  - BACKGROUND: Immune priming has been shown to occur in a wide array of
      invertebrate taxa, with individuals exposed to a pathogen showing increased
      protection upon subsequent exposure. However, the mechanisms underlying immune
      priming are poorly understood. The antiviral RNAi response in Drosophila
      melanogaster is an ideal candidate for providing a specific and acquired response
      to subsequent infection. We exposed D. melanogaster to two challenges of a virus
      known to produce an antiviral RNAi response, to examine whether any protective
      effects of prior exposure on survival were observed. RESULTS: In this experiment
      we found no evidence that prior exposure to Drosophila C Virus (DCV) protects
      flies from a subsequent lethal challenge, with almost identical levels of
      mortality in flies previously exposed to DCV or a control. CONCLUSIONS: Our
      results confirm the finding that 'acquired' immune responses are not ubiquitous
      across all invertebrate-pathogen interactions. We discuss why we may have
      observed no effect in this study, with focus on the mechanistic basis of the RNAi
      pathway.

PMID- 24040087
TI  - Functional characterization of a juvenile hormone esterase related gene in the
      moth Sesamia nonagrioides through RNA interference.
AB  - Juvenile hormone esterase (JHE) is a carboxylesterase that has attracted great
      interest because of its critical role in regulating larval to adult transition in
      insects and other arthropods. Previously, we characterized an ecdysteroid
      sensitive and juvenile hormone non-susceptible juvenile hormone esterase related
      gene (SnJHER) in the corn stalk borer, Sesamia nonagrioides. SnJHER was
      rhythmically up-regulated close to each molt during the corn stalk borer's larval
      development. In this paper we attempted to functionally characterize SnJHER using
      several reverse genetics techniques. To functionally characterize SnJHER, we
      experimented with different dsRNA administration methods, including hemolymph,
      bacterial or baculovirus-mediated RNA interference, (RNAi). Our findings indicate
      the potential implication of SnJHER in the developmental programming of Sesamia
      nonagrioides. It is still unclear whether SnJHER is closely related to the
      authentic JHE gene, with different or similar biological functions. 

PMID- 24040088
TI  - Membrane lipid-modulated mechanism of action and non-cytotoxicity of novel
      fungicide aminoglycoside FG08.
AB  - A novel aminoglycoside, FG08, that differs from kanamycin B only by a C8 alkyl
      chain at the 4"-O position, was previously reported. Unlike kanamycin B, FG08
      shows broad-spectrum fungicidal but not anti-bacterial activities. To understand
      its specificity for fungi, the mechanism of action of FG08 was studied using
      intact cells of the yeast Saccharomyces cerevisiae and small unilamellar membrane
      vesicles. With exposure to FG08 (30 ug mL(-1)), 8-fold more cells were stained
      with fluorescein isothiocyanate, cells had 4 to 6-fold higher K(+) efflux rates,
      and 18-fold more cells were stained with SYTOX Green in comparison to exposure to
      kanamycin B (30 ug mL(-1)). Yeast mutants with aberrant membrane sphingolipids
      (no sphingoid base C4 hydroxyl group, truncated very long fatty acid chain, or
      lacking the terminal phosphorylinositol group of mannosyl
      diinositolphosphorylphytoceramide were 4 to 8-fold less susceptible to growth
      inhibition with FG08 and showed 2 to 10-fold lower SYTOX Green dye uptake rates
      than did the isogenic wild-type strain. FG08 caused leakage of pre-loaded calcein
      from 50% of small unilamellar vesicles with glycerophospholipid and sterol
      compositions that mimic the compositions of fungal plasma membranes. Less than 5
      and 10% of vesicles with glycerophospholipid and sterol compositions that mimic
      bacterial and mammalian cell plasma membranes, respectively, showed calcein
      leakage. In tetrazolium dye cytotoxicity tests, mammalian cell lines NIH3T3 and
      C8161.9 showed FG08 toxicity at concentrations that were 10 to 20-fold higher
      than fungicidal minimal inhibitory concentrations. It is concluded that FG08's
      growth inhibitory specificity for fungi lie in plasma membrane permeability
      changes involving mechanisms that are modulated by membrane lipid composition. 

PMID- 24040089
TI  - Recovery of barotrauma injuries resulting from exposure to pile driving sound in
      two sizes of hybrid striped bass.
AB  - The effects of loud sounds on fishes, such as those produced during impulsive
      pile driving, are an increasing concern in the management of aquatic ecosystems.
      However, very little is known about such effects. Accordingly, a High Intensity
      Controlled Impedance Fluid Filled wave Tube (HICI-FT) was used to investigate the
      effects of sounds produced by impulsive pile driving on two size groups of hybrid
      striped bass (white bass Moronechrysops x striped bass Moronesaxatilis). The
      larger striped bass (mean size 17.2 g) had more severe injuries, as well as more
      total injuries, than the smaller fish (mean size 1.3 g). However, fish in each
      size group recovered from most injuries within 10 days of exposure. A comparison
      with different species from previously published studies show that current
      results support the observation that fishes with physoclistous swim bladders are
      more susceptible to injury from impulsive pile driving than are fishes with
      physostomous swim bladders. 

PMID- 24040090
TI  - Evaluation of inhibitor-resistant real-time PCR methods for diagnostics in
      clinical and environmental samples.
AB  - Polymerase chain reaction (PCR) is commonly used for pathogen detection in
      clinical and environmental samples. These sample matrices often contain
      inhibitors of PCR, which is a primary reason for sample processing; however, the
      purification process is highly inefficient, becoming unacceptable at lower
      signature concentrations. One potential solution is direct PCR assessment without
      sample processing. Here, we evaluated nine inhibitor-resistant PCR reagents for
      direct detection of Francisella tularensis in seven different clinical and
      environmental samples using an established real-time PCR assay to assess ability
      to overcome PCR inhibition. While several of these reagents were designed for
      standard PCR, the described inhibitor resistant properties (ex. Omni Klentaq can
      amplify target DNA samples of up to 20% whole blood or soil) led to our
      evaluation with real-time PCR. A preliminary limit of detection (LOD) was
      determined for each chemistry in whole blood and buffer, and LODs (20 replicates)
      were determined for the top five chemistries in each matrix (buffer, whole blood,
      sputum, stool, swab, soil, and sand). Not surprisingly, no single chemistry
      performed the best across all of the different matrices evaluated. For instance,
      Phusion Blood Direct PCR Kit, Phire Hot Start DNA polymerase, and Phire Hot Start
      DNA polymerase with STR Boost performed best for direct detection in whole blood
      while Phire Hot Start DNA polymerase with STR Boost were the only reagents to
      yield an LOD in the femtogram range for soil. Although not the best performer
      across all matrices, KAPA Blood PCR kit produced the most consistent results
      among the various conditions assessed. Overall, while these inhibitor resistant
      reagents show promise for direct amplification of complex samples by real-time
      PCR, the amount of template required for detection would not be in a clinically
      relevant range for most matrices. 

PMID- 24040091
TI  - Early changes of neuromuscular transmission in the SOD1(G93A) mice model of ALS
      start long before motor symptoms onset.
AB  - Amyotrophic lateral sclerosis is characterized by a progressive degeneration of
      the corticospinal tract motor neurons. Growing evidence suggests that
      degeneration may begin at the distal axon proceeding in a dying-back pattern. It
      seemed therefore of interest to investigate synaptic transmission at the
      neuromuscular junction (NMJ) in pre- and symptomatic phases of the disease.
      Endplate potentials (EPPs), miniatures endplate potentials (MEPPs) and giant
      MEPPs (GMEPPs) were recorded from innervated diaphragm muscle fibers from 4-6 and
      12-15 weeks-old SOD1(G93A) mice and non-transgenic aged-matched littermates (WT).
      In the pre-symptomatic phase, SOD1(G93A) mice exhibited a significant increase in
      the mean amplitude of EPPs together with an increase in the mean quantal content
      of EPPs, suggesting that more acetylcholine is being released into the synaptic
      cleft. SOD1(G93A) mice presented a higher frequency of GMEPPs, suggestive of
      intracellular Ca(2+) deregulation in nerve terminals. The increase in the mean
      amplitude of MEPPs and the decreased mean rise-time of MEPPs in SOD1(G93A) mice
      point to post-synaptic related changes. In the symptomatic phase,
      electrophysiological data showed evidence for two NMJ groups in SOD1(G93A) mice:
      SOD1a and SOD1b. SOD1a group presented reduced mean amplitude of both EPPs and
      MEPPs. The mean rise-time of MEPPs was increased, when compared to WT and to
      SOD1b group, indicating impairments in the neuromuscular transmission. In
      contrast, the neuromuscular transmission of SOD1b group was not different from
      age-matched WT nor pre-symptomatic SOD1(G93A) mice, being somehow in between both
      groups. Altogether these results show that the neuromuscular transmission of
      SOD1(G93A) mice is enhanced in the pre-symptomatic phase. In the symptomatic
      phase our results are consistent with the hypothesis that the diaphragm of
      SOD1(G93A) mice is undergoing cycles of denervation/re-innervation supported by
      mixed neuromuscular junction populations. These early changes in the
      neuromuscular transmission of SOD1(G93A) mice suggest that the ALS associated
      events start long before symptoms onset. 

PMID- 24040092
TI  - Proteolytic pathways induced by herbicides that inhibit amino acid biosynthesis.
AB  - BACKGROUND: The herbicides glyphosate (Gly) and imazamox (Imx) inhibit the
      biosynthesis of aromatic and branched-chain amino acids, respectively. Although
      these herbicides inhibit different pathways, they have been reported to show
      several common physiological effects in their modes of action, such as increasing
      free amino acid contents and decreasing soluble protein contents. To investigate
      proteolytic activities upon treatment with Gly and Imx, pea plants grown in
      hydroponic culture were treated with Imx or Gly, and the proteolytic profile of
      the roots was evaluated through fluorogenic kinetic assays and activity-based
      protein profiling. RESULTS: Several common changes in proteolytic activity were
      detected following Gly and Imx treatment. Both herbicides induced the ubiquitin
      26 S proteasome system and papain-like cysteine proteases. In contrast, the
      activities of vacuolar processing enzymes, cysteine proteases and metacaspase 9
      were reduced following treatment with both herbicides. Moreover, the activities
      of several putative serine protease were similarly increased or decreased
      following treatment with both herbicides. In contrast, an increase in YVADase
      activity was observed under Imx treatment versus a decrease under Gly treatment.
      CONCLUSION: These results suggest that several proteolytic pathways are
      responsible for protein degradation upon herbicide treatment, although the
      specific role of each proteolytic activity remains to be determined.

PMID- 24040093
TI  - Correlations between colonization of onion thrips and leaf reflectance measures
      across six cabbage varieties.
AB  - The main purpose of this study was to reveal if the UV-A, and visible light
      reflection of leaves of white cabbage varieties is correlated to resistance
      against onion thrips. The antixenotic resistance (AR) against onion thrips and
      thrips damage differed between varieties Balashi, Bloktor, Riana - considered
      resistant - and Green Gem, Hurricane, Quisor - considered susceptible. The solar
      UV-A (340-400 nm) and visible (401-650 nm) light reflection of white cabbage
      leaves were recorded. Correlation between AR against onion thrips and reflection
      of leaves in UV-A and visible range of the studied white cabbage varieties were
      computed. According to the AR evaluation onion thrips density was always higher
      on susceptible than on resistant varieties. The UV-A light reflection of head
      forming leaves and the contrast between head and exterior leaves (H/E) was
      negatively correlated with onion thrips host preference at an early stage of
      cabbage head formation. The visible light reflection of both head forming and
      exterior leaves was also negatively correlated with onion thrips host preference.
      Susceptible varieties had greater damage ratings at harvest than resistant ones
      and positive correlations were observed between AR and damage. AR against onion
      thrips may be affected by differences in reflection of cabbage leaves at an early
      growth stage. It is suggested that more intensive reflection of leaves and/or
      higher contrast values between the reflectance intensity of head versus outer
      leaves made the resistant varieties less attractive to onion thrips. Our results
      reported here provide the first evidence of negative correlation between UV-A and
      visible reflection of leaves and AR of white cabbage against a dangerous insect
      pest, opening new perspectives for understanding the role of reflection by plant
      leaves in pest management.

PMID- 24040094
TI  - Intra- and inter-brain synchronization during musical improvisation on the
      guitar.
AB  - Humans interact with the environment through sensory and motor acts. Some of
      these interactions require synchronization among two or more individuals.
      Multiple-trial designs, which we have used in past work to study interbrain
      synchronization in the course of joint action, constrain the range of observable
      interactions. To overcome the limitations of multiple-trial designs, we conducted
      single-trial analyses of electroencephalography (EEG) signals recorded from eight
      pairs of guitarists engaged in musical improvisation. We identified hyper-brain
      networks based on a complex interplay of different frequencies. The intra-brain
      connections primarily involved higher frequencies (e.g., beta), whereas inter
      brain connections primarily operated at lower frequencies (e.g., delta and
      theta). The topology of hyper-brain networks was frequency-dependent, with a
      tendency to become more regular at higher frequencies. We also found hyper-brain
      modules that included nodes (i.e., EEG electrodes) from both brains. Some of the
      observed network properties were related to musical roles during improvisation.
      Our findings replicate and extend earlier work and point to mechanisms that
      enable individuals to engage in temporally coordinated joint action. 

PMID- 24040095
TI  - Ficolin-2 defends against virulent Mycobacteria tuberculosis infection in vivo,
      and its insufficiency is associated with infection in humans.
AB  - Human ficolin-2 (ficolin-2/P35) is a lectin complement pathway activator that is
      present in normal human plasma and is associated with infectious diseases;
      however, little is known regarding the roles and mechanisms of ficolin-2 during
      Mycobacterium tuberculosis (Mtb) infection. Here, we describe our novel findings
      that the ficolin-2 serum levels of 107 pulmonary tuberculosis (TB) patients were
      much lower compared with 107 healthy controls. In vitro analysis showed that
      ficolin-2 bound to the virulent Mtb H37Rv strain much more strongly than to the
      non-virulent M. bovis BCG and M. smegmatis. Ficolin-2 bound to the surface
      glycolipid portion of H37Rv and blocked H37Rv infection in human lung A549 cells.
      Opsonophagocytosis was also promoted by ficolin-2. Importantly, we found that
      administration of exogenous ficolin-2 had a remarkable protective effect against
      virulent Mtb H37Rv infection in both C57BL/6J and BALB/c mice. Ficolin-A (a
      ficolin-2-like molecule in mouse) knockout mice exhibited increased
      susceptibility to H37Rv infection. We further demonstrated that ficolin-2 could
      defend against virulent Mtb H37Rv infection at least partially by activating JNK
      phosphorylation and stimulating the secretion of interferon (IFN)-gamma,
      interleukin (IL)-17, IL-6, tumor necrosis factor (TNF)-alpha, and nitric oxide
      (NO) production by macrophages. Our data provide a new immunotherapeutic strategy
      against TB based on the innate immune molecule ficolin-2 and indicate that
      ficolin-2 insufficiency is associated with higher susceptibility to infection in
      humans.

PMID- 24040096
TI  - Local targeted therapy of liver metastasis from colon cancer by galactosylated
      liposome encapsulated with doxorubicin.
AB  - Since regional drug administration enables to maintain a high drug concentration
      within tumors, we compared the plasma concentration and biodistribution of
      doxorubicin (Dox) from drug-loaded conventional liposomes by local or systemic
      administration. The results demonstrated that drug concentration was
      substantially improved in liver as well as a decrease in blood and other organs
      by spleen injection mimicking portal vein perfusion (regional administration). To
      further investigate the targeted therapeutic effect of galactosylated liposome
      encapsulated doxorubicin (Dox) by regional administration, liver targeting
      liposomes were prepared by incorporating galactosylated-DPPE to conventional
      liposomes. Liposome uptake and targeting were verified in vitro and in vivo by
      fluorescence microscopy and xenogen IVIS imaging system, respectively. The
      results showed that galactose targeted liposomes presented a stronger specific
      cell uptake by human hepatocellular carcinoma HepG2 cells compared to the non
      targeted liposomes. In vivo fluorescence imaging showed that the intra-hepatic
      deposition of conventional and galactosylated liposomes via spleen injection was
      more than that via tail vein administration, and galactosylated liposomes had
      higher fluorescent intensity over conventional liposomes in the liver post spleen
      administration. The anti-tumor effect of various drug administration routes for
      both liposomal formulations was evaluated using a murine liver metastasis model
      of colon cancer. The results indicated that tumor progression in the liver and
      mesenteric lymph nodes was significantly suppressed by Dox-loaded galactosylated
      liposomes via spleen injection, while no significance was observed in non
      targeted formulations. Our data indicated that local perfusion of galactosylated
      liposomal doxorubicin had a great promise for the treatment of liver metastasis
      from colon cancer. 

PMID- 24040097
TI  - Equity in maternal health in South Africa: analysis of health service access and
      health status in a national household survey.
AB  - BACKGROUND: South Africa is increasingly focused on reducing maternal mortality.
      Documenting variation in access to maternal health services across one of the
      most inequitable nations could assist in re-direction of resources. METHODS:
      Analysis draws on a population-based household survey that used multistage
      stratified sampling. Women, who in the past two years were pregnant (1113) or had
      a child (1304), completed questionnaires and HIV testing. Distribution of access
      to maternal health services and health status across socio-economic, education
      and other population groups was assessed using weighted data. FINDINGS: Poorest
      women had near universal antenatal care coverage (ANC), but only 39.6% attended
      before 20 weeks gestation; this figure was 2.7-fold higher in the wealthiest
      quartile (95%CI adjusted odds ratio = 1.2-6.1). Women in rural-formal areas had
      lowest ANC coverage (89.7%), percentage completing four ANC visits (79.7%) and
      only 84.0% were offered HIV testing. Testing levels were highest among the
      poorest quartile (90.1% in past two years), but 10% of women above 40 or with low
      education had never tested. Skilled birth attendant coverage (overall 95.3%) was
      lowest in the poorest quartile (91.4%) and rural formal areas (85.6%). Around two
      thirds of the wealthiest quartile, of white and of formally-employed women had a
      doctor at childbirth, 11-fold higher than the poorest quartile. Overall, only
      44.4% of pregnancies were planned, 31.7% of HIV-infected women and 68.1% of the
      wealthiest quartile. Self-reported health status also declined considerably with
      each drop in quartile, education level or age group. CONCLUSIONS: Aside from
      early ANC attendance and deficiencies in care in rural-formal areas, inequalities
      in utilisation of services were mostly small, with some measures even highest
      among the poorest. Considerably larger differences were noted in maternal health
      status across population groups. This may reflect differences between these
      groups in quality of care received, HIV infection and in social determinants of
      health.

PMID- 24040098
TI  - SIL-TAL1 rearrangement is related with poor outcome: a study from a Chinese
      institution.
AB  - SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL),
      however its prognostic implication remains controversial. To investigate the
      clinical characteristics and outcome of this subtype in Chinese population, we
      systemically reviewed 62 patients with newly diagnosed T-ALL, including 15
      patients with SIL-TAL1 rearrangement. We found that SIL-TAL1(+) T-ALL was
      characterized by higher white blood cell count (P = 0.029) at diagnosis,
      predominant cortical T-ALL immunophenotype (P = 0.028) of the leukemic blasts,
      and a higher prevalence of tumor lysis syndrome (TLS, P<0.001) and disseminated
      intravascular coagulation (DIC, P<0.001), which led to a higher early mortality
      (P = 0.011). Compared with SIL-TAL1(-) patients, SIL-TAL1(+) patients had shorter
      relapse free survival (P = 0.007) and overall survival (P = 0.002). Our NOD/SCID
      xenotransplantation model also demonstrated that SIL-TAL1(+) mice models had
      earlier disease onset, higher leukemia cell load in peripheral blood and shorter
      overall survival (P<0.001). Moreover, the SIL-TAL1(+) mice models exerted a
      tendency of TLS/DIC and seemed vulnerable towards chemotherapy, which further
      simulated our clinical settings. These data demonstrate that SIL-TAL1
      rearrangement identifies a distinct subtype with inferior outcome which could
      allow for individual therapeutic stratification for T-ALL patients.

PMID- 24040099
TI  - Overexpression of arginine transporter CAT-1 is associated with accumulation of L
      arginine and cell growth in human colorectal cancer tissue.
AB  - We previously showed that L-arginine (Arg) accumulates in colorectal cancer
      tissues. The aim of this study was to investigate the mechanism by which Arg
      accumulates and determine its biological significance. The concentration of Arg
      and Citrulline (Cit) in sera and tumor tissues from colorectal cancer (CRC)
      patients was analyzed by high-performance liquid chromatography (HPLC). The
      expression of Arg transporters was analyzed by quantitative reverse transcription
      polymerase chain reaction (qRT-PCR) and immunohistochemical analysis of tissue
      microarray. We also transfected the colon cancer cell line HCT-116 with siRNA
      specific for the Arg transporter CAT-1 and measured the induction of apoptosis by
      flow cytometry and cell proliferation by MTT assay. Consistent with our previous
      results, serum Arg and Cit concentrations in colorectal cancer patients were
      significantly lower than those in normal volunteers, while Arg and Cit
      concentrations in colorectal cancer tissues were significantly higher than in
      matched adjacent normal colon tissues. Quantitative RT-PCR showed that the CAT-1
      gene was highly overexpressed in 70.5% of colorectal cancer tissue samples
      relative to adjacent normal colon tissues in all 122 patients with colorectal
      cancer. Immunohistochemical analysis of tissue microarray confirmed that the
      expression of CAT-1 was higher in all 25 colorectal cancer tissues tested. CAT-1
      siRNA significantly induced apoptosis of HCT-116 cells and subsequently inhibited
      cell growth by 20-50%. Our findings indicate that accumulation of L-Arg and Cit
      and cell growth in colorectal cancer tissues is associated with over-expression
      of the Arg transporter gene CAT-1. Our results may be useful for the development
      of molecular diagnostic tools and targeted therapy for colorectal cancer. 

PMID- 24040100
TI  - Gastric antimicrobial peptides fail to eradicate Helicobacter pylori infection
      due to selective induction and resistance.
AB  - BACKGROUND: Although antimicrobial peptides protect mucus and mucosa from
      bacteria, Helicobacter pylori is able to colonize the gastric mucus. To clarify
      in which extend Helicobacter escapes the antimicrobial defense, we systematically
      assessed susceptibility and expression levels of different antimicrobial host
      factors in gastric mucosa with and without H. pylori infection. MATERIALS AND
      METHODS: We investigated the expression levels of HBD1 (gene name DEFB1), HBD2
      (DEFB4A), HBD3 (DEFB103A), HBD4 (DEFB104A), LL37 (CAMP) and elafin (PI3) by real
      time PCR in gastric biopsy samples in a total of 20 controls versus 12 patients
      colonized with H. pylori. Immunostaining was performed for HBD2 and HBD3. We
      assessed antimicrobial susceptibility by flow cytometry, growth on blood agar,
      radial diffusion assay and electron microscopy. RESULTS: H. pylori infection was
      associated with increased gastric levels of the inducible defensin HBD2 and of
      the antiprotease elafin, whereas the expression levels of the constitutive
      defensin HBD1, inducible HBD3 and LL37 remained unchanged. HBD4 was not expressed
      in significant levels in gastric mucosa. H. pylori strains were resistant to the
      defensins HBD1 as well as to elafin, and strain specific minimally susceptible to
      HBD2, whereas HBD3 and LL37 killed all H. pylori strains effectively. We
      demonstrated the binding of HBD2 and LL37 on the surface of H. pylori cells.
      Comparing the antibacterial activity of extracts from H. pylori negative and
      positive biopsies, we found only a minimal killing against H. pylori that was not
      increased by the induction of HBD2 in H. pylori positive samples. CONCLUSION:
      These data support the hypothesis that gastric H. pylori evades the host defense
      shield to allow colonization.

PMID- 24040101
TI  - Antigen-specific suppression and immunological synapse formation by regulatory T
      cells require the Mst1 kinase.
AB  - Although the cell-to-cell contact between CD4(+)Foxp3(+) regulatory T (Treg) and
      their target cells is important for the suppressor function of Treg cells, the
      regulation of this process is not well understood. Here we show that the Mst1
      kinase plays a critical role in the suppressor function of Treg cells through
      regulation of cell contact dependent processes. Mst1 (-/-) Treg cells failed to
      prevent the development of experimental colitis and antigen-specific suppression
      of naive T cells proliferation in vitro. Mst1 (-/-) Treg cells exhibited
      defective interactions with antigen-presenting dendritic cells (DCs), resulting
      in reduced down-regulation of costimulatory molecules. While wild-type CD4(+)
      Foxp3(+) Treg cells formed mobile immunological synapses on supported planar
      membrane, Mst1 (-/-) Treg cells did not exhibit ICAM-1 ring or central peptide
      MHC clustering. Using two-photon imaging we showed that antigen-specific wild
      type Treg cells exhibited dynamic mobile contacts with antigen-pulsed DCs bearing
      stably associated naive T cells. In contrast, Mst1 (-/-) Treg had impairments in
      their interactions with DCs. Thus, Mst1 is required for Treg cells to mediate
      contact-dependent suppressor functions. 

PMID- 24040102
TI  - Regulation of FOXOs and p53 by SIRT1 modulators under oxidative stress.
AB  - Excessive reactive oxygen species (ROS) induce apoptosis and are associated with
      various diseases and with aging. SIRT1 (sirtuin-1), an NAD+-dependent protein
      deacetylase, decreases ROS levels and participates in cell survival under
      oxidative stress conditions. SIRT1 modulates the transcription factors p53, a
      tumor suppressor and inducer of apoptosis, and the forkhead O (FOXO) family, both
      of which play roles for cell survival and cell death. In this study, we aimed to
      know which is working greatly among p53 and FOXOs transcription factors in
      SIRT1's cell protective functions under oxidative stress conditions. The
      antimycin A-induced increase in ROS levels and apoptosis was enhanced by SIRT1
      inhibitors nicotinamide and splitomicin, whereas it was suppressed by a SIRT1
      activator, resveratrol, and a SIRT1 cofactor, NAD+. SIRT1-siRNA abolished the
      effects of splitomicin and resveratrol. p53-knockdown experiment in C2C12 cells
      and experiment using p53-deficient HCT116 cells showed that splitomicin and
      resveratrol modulated apoptosis by p53-dependent and p53-independent pathways. In
      p53-independent cell protective pathway, we found that FOXO1, FOXO3a, and FOXO4
      were involved in SOD2's upregulation by resveratrol. The knockdown of these three
      FOXOs by siRNAs completely abolished the SOD2 induction, ROS reduction, and anti
      apoptotic function of resveratrol. Our results indicate that FOXO1, FOXO3a and
      FOXO4, are indispensable for SIRT1-dependent cell survival against oxidative
      stress, although deacetylation of p53 has also some role for cell protective
      function of SIRT1. 

PMID- 24040103
TI  - Methicillin-resistant Staphylococcus aureus in Saarland, Germany: a statewide
      admission prevalence screening study.
AB  - BACKGROUND: The screening of hospital admission patients for methicillin
      resistant Staphylococcus aureus (MRSA) is of undisputed value in controlling and
      reducing the overall MRSA burden; yet, a concerted parallel universal screening
      intervention throughout all hospitals of an entire German Federal State has not
      yet been performed. METHODOLOGY/PRINCIPAL FINDINGS: During a four-week period,
      all 24 acute care hospitals of the State of Saarland participated in admission
      prevalence screening. Overall, 436/20,027 screened patients revealed MRSA carrier
      status (prevalence, 2.2/100 patients) with geriatrics and intensive care
      departments associated with highest prevalence (7.6/100 and 6.3/100,
      respectively). Risk factor analysis among 17,975 admission patients yielded MRSA
      history (OR, 4.3; CI95 2.7-6.8), a skin condition (OR, 3.2; CI95 2.1-5.0), and/or
      an indwelling catheter (OR, 2.2; CI95 1.4-3.5) among the leading risks.
      Hierarchical risk factor ascertainment of the six risk factors associated with
      highest odd's ratios would require 31% of patients to be laboratory screened to
      allow for detection of 67% of all MRSA positive admission patients in the State.
      CONCLUSIONS/SIGNIFICANCE: State-wide admission prevalence screening in
      conjunction with risk factor ascertainment yields important information on the
      distribution of the MRSA burden for hospitals, and allows for data-based
      decisions on local or institutional MRSA screening policies considering risk
      factor prevalence and expected MRSA identification rates.

PMID- 24040104
TI  - Vicarious neural processing of outcomes during observational learning.
AB  - Learning what behaviour is appropriate in a specific context by observing the
      actions of others and their outcomes is a key constituent of human cognition,
      because it saves time and energy and reduces exposure to potentially dangerous
      situations. Observational learning of associative rules relies on the ability to
      map the actions of others onto our own, process outcomes, and combine these
      sources of information. Here, we combined newly developed experimental tasks and
      functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms
      that govern such observational learning. Results show that the neural systems
      involved in individual trial-and-error learning and in action observation and
      execution both participate in observational learning. In addition, we identified
      brain areas that specifically activate for others' incorrect outcomes during
      learning in the posterior medial frontal cortex (pMFC), the anterior insula and
      the posterior superior temporal sulcus (pSTS). 

PMID- 24040105
TI  - BMCC1 is an AP-2 associated endosomal protein in prostate cancer cells.
AB  - The prostate cancer antigen gene 3 (PCA3) is embedded in an intron of a second
      gene BMCC1 (Bcl2-/adenovirus E1B nineteen kDa-interacting protein 2 (BNIP-2) and
      Cdc42GAP homology BCH motif-containing molecule at the carboxyl terminal region
      1) which is also upregulated in prostate cancer. BMCC1 was initially annotated as
      two genes (C9orf65/PRUNE and BNIPXL) on either side of PCA3 but our data suggest
      that it represents a single gene coding for a high molecular weight protein. Here
      we demonstrate for the first time the expression of a >300 kDa BMCC1 protein
      (BMCC1-1) in prostate cancer and melanoma cell lines. This protein was found
      exclusively in the microsomal fraction and localised to cytoplasmic vesicles. We
      also observed expression of BMCC1 protein in prostate cancer sections using
      immunohistology. GST pull down, immunoprecipitation and mass spectrometry protein
      interaction studies identified multiple members of the Adaptor Related Complex 2
      (AP-2) as BMCC1 interactors. Consistent with a role for BMCC1 as an AP-2
      interacting endosomal protein, BMCC1 co-localised with beta-adaptin at the
      perinuclear region of the cell. BMCC1 also showed partial co-localisation with
      the early endosome small GTP-ase Rab-5 as well as strong co-localisation with
      internalised pulse-chase labelled transferrin (Tf), providing evidence that BMCC1
      is localised to functional endocytic vesicles. BMCC1 knockdown did not affect Tf
      uptake and AP-2 knockdown did not disperse BMCC1 vesicular distribution,
      excluding an essential role for BMCC1 in canonical AP-2 mediated endocytic
      uptake. Instead, we posit a novel role for BMCC1 in post-endocytic trafficking.
      This study provides fundamental characterisation of the BMCC1 complex in prostate
      cancer cells and for the first time implicates it in vesicle trafficking. 

PMID- 24040106
TI  - SUN family proteins Sun4p, Uth1p and Sim1p are secreted from Saccharomyces
      cerevisiae and produced dependently on oxygen level.
AB  - The SUN family is comprised of proteins that are conserved among various yeasts
      and fungi, but that are absent in mammals and plants. Although the function(s) of
      these proteins are mostly unknown, they have been linked to various, often
      unrelated cellular processes such as those connected to mitochondrial and cell
      wall functions. Here we show that three of the four Saccharomyces cerevisiae SUN
      family proteins, Uth1p, Sim1p and Sun4p, are efficiently secreted out of the
      cells in different growth phases and their production is affected by the level of
      oxygen. The Uth1p, Sim1p, Sun4p and Nca3p are mostly synthesized during the
      growth phase of both yeast liquid cultures and colonies. Culture transition to
      slow-growing or stationary phases is linked with a decreased cellular
      concentration of Sim1p and Sun4p and with their efficient release from the cells.
      In contrast, Uth1p is released mainly from growing cells. The synthesis of Uth1p
      and Sim1p, but not of Sun4p, is repressed by anoxia. All four proteins confer
      cell sensitivity to zymolyase. In addition, Uth1p affects cell sensitivity to
      compounds influencing cell wall composition and integrity (such as Calcofluor
      white and Congo red) differently when growing on fermentative versus respiratory
      carbon sources. In contrast, Uth1p is essential for cell resistance to boric
      acids irrespective of carbon source. In summary, our novel findings support the
      hypothesis that SUN family proteins are involved in the remodeling of the yeast
      cell wall during the various phases of yeast culture development and under
      various environmental conditions. The finding that Uth1p is involved in cell
      sensitivity to boric acid, i.e. to a compound that is commonly used as an
      important antifungal in mycoses, opens up new possibilities of investigating the
      mechanisms of boric acid's action. 

PMID- 24040107
TI  - Internal ribosome entry segment activity of ATXN8 opposite strand RNA.
AB  - Spinocerebellar ataxia type 8 (SCA8) involves the expansion of CTG/CAG repeats
      from the overlapping ataxin 8 opposite strand (ATXN8OS) and ataxin 8 (ATXN8)
      genes located on chromosome 13q21. Although being transcribed, spliced and
      polyadenylated in the CTG orientation, ATXN8OS does not itself appear to be
      protein coding, as only small open reading frames (ORFs) were noted. In the
      present study we investigated the translation of a novel 102 amino acids
      containing-ORF in the ATXN8OS RNA. Expression of chimeric construct with an in
      frame ORF-EGFP gene demonstrated that ATXN8OS RNA is translatable. Using
      antiserum raised against ORF, ATXN8OS ORF expression was detected in various
      human cells including lymphoblastoid, embryonic kidney 293, neuroblastoma IMR-32,
      SK-N-SH, SH-SY5Y cells and human muscle tissue. The biological role of the
      ATXN8OS ORF and its connection to SCA8 remains to be determined. 

PMID- 24040108
TI  - PIKfyve regulates the endosomal localization of CpG oligodeoxynucleotides to
      elicit TLR9-dependent cellular responses.
AB  - TLR9 is a receptor for oligodeoxynucleotides that contain unmethylated CpG motifs
      (CpG). Because TLR9 resides in the endoplasmic reticulum during the quiescence
      state, CpG binding to TLR9 requires membrane trafficking, which includes the
      maturation of the CpG-containing endosome. In the present study, we examined the
      role of PIKfyve, a phosphatidylinositol 3-phosphate 5-kinase, in the regulation
      of TLR9 signaling. The PIKfyve inhibitor YM201636 inhibited co-localization of
      the CpG-containing endosome with LysoTracker, which stains acidic organelle, and
      with TLR9. YM201636 increased the co-localization of CpG with the early endosome
      marker EEA1 but decreased co-localization with the late endosome marker LAMP1.
      Similar results were obtained in Raw264.7 cells containing shRNA that targets
      PIKfyve. CpG-mediated phosphorylation but not lipopolysaccharide (LPS)-mediated
      phosphorylation of IKK, p38 MAPK, JNK and Stat3 was severely impaired by the loss
      of PIKfyve function. CpG-mediated expression of cytokine mRNA was also decreased
      in the absence of PIKfyve. These findings demonstrate a novel role of PIKfyve in
      TLR9 signaling. 

PMID- 24040109
TI  - Potential risk of asymptomatic osteomyelitis around mandibular third molar tooth
      for aged people: a computed tomography and histopathologic study.
AB  - The purpose of this study was to explore the relationship between bone mineral
      density and histopathological features of mandibular alveolar bone evaluated
      quantitatively by Hounsfield units [HU] and by histopathology in human subjects.
      Fifty-six mandibular molars were extracted in 50 patients. Computed tomography
      was obtained preoperatively, and a cortical bone biopsy was obtained on the
      extracted sites for histopathological evaluation. The mean cortical and
      cancellous bone radiodensity was 1846 +/- 118 HU and 926 +/- 436 HU,
      respectively. There was no correlation between age and cortical bone HU (r = 
      0.004, P = 0.976); however, the correlation between age and cancellous bone HU
      was significant (r = 0.574, P<0.0000). Significant differences in the cancellous
      bone between young (0-30 years), middle (31-60 years) and old patient groups (61<
      years) were evident (P<0.05), whereas the cortical bone presented no significant
      differences. The histopathological evaluation showed that the young patient group
      had relatively few osteomyelitis, whereas the old patient group showed 100% focal
      sclerotic osteomyelitis regardless of the fact that the patients had no clinical
      symptoms. The mean osteocyte number/unit bone area was 170.7 +/- 82.2. Negative
      correlation between age and osteocyte number was significant (r = -0.51,
      P<0.0001). Mean lacunae numbers/unit cortical bone area were 413.1 +/- 130 with
      non-significant negative correlation (r = -0.257, P = 0.056). The mean empty
      lacunae numbers/cortical bone were 242.5+/-145, with no correlation (r = 0.081, P
      = 0.559). The young patients had high osteocyte number, whereas the old patients
      showed reduction of the osteocytes in the cortical bone (P < 0.05). Bone quality
      might correlate better to viable cell numbers, which influenced the osseous
      healing. It is suggested that the outermost layer of cortical bone may have lost
      its cellular activities over the years due to chronic infection, which may have
      provoked sclerotic changes in the cancellous bone around tooth.

PMID- 24040110
TI  - Survival and hsp70 gene expression in Plutella xylostella and its larval
      parasitoid Diadegma insulare varied between slowly ramping and abrupt extreme
      temperature regimes.
AB  - BACKGROUND: In nature, insects have evolved behavioural and physiological
      adaptations to cope with short term exposure to extreme temperatures. Extreme
      heat events may increase as a result of climate change; this in turn will affect
      insect population dynamics. We examined the effect of abrupt and ecologically
      relevant gradual exposure to high temperatures on the survival and hsp70 gene
      expression in diamondback moth (DBM) adults and the parasitoid Diadegma insulare,
      as well as in parasitized and non-parasitized DBM larvae. PRINCIPAL FINDINGS:
      Tolerance to high temperatures in DBM adults was higher than in D. insulare
      adults. There was no difference in the survival of DBM adults between abrupt and
      ramped increases from 25 to 38 degrees C; however, at 40 degrees C survival was
      higher when the temperature increased gradually. In contrast, more D. insulare
      adults survived when the temperature was ramped rather than shifted abruptly to
      both 38 and 40 degrees C. There was no heat stress effect of up to 40 degrees C
      on the survival of either parasitized or non-parasitized DBM larvae. In adults of
      both species, more hsp70 expression was observed when temperatures increased
      abruptly to 38 degrees C compared to ramping. In contrast, at 40 degrees C
      significantly more expression was found in insects exposed to the ramping rather
      than the abrupt regime. Hsp70 expression level was in agreement with adult
      survival data and appears to be a good indicator of stress levels. In parasitized
      and non-parasitized larvae, hsp70 expression was significantly higher after
      abrupt shifts compared to ramping at both temperatures. CONCLUSIONS/SIGNIFICANCE:
      Hsp70 gene expression was responsive to extreme temperatures in both DBM and D.
      insulare, which may underlie the ability of these insects to survive in extreme
      temperatures. Survival and hsp70 expression upon abrupt changes are distinctly
      different from those after ramping indicating that experimental protocol must be
      considered before extrapolating laboratory results to natural field situations.

PMID- 24040111
TI  - Increased turnover of dopamine in caudate nucleus of detoxified alcoholic
      patients.
AB  - A previous study of the DOPA decarboxylase substrate 6-[(18)F]fluoro-L-DOPA
      (FDOPA) with positron emission tomography (PET) detected no difference of the net
      blood-brain transfer rate (Kin(app)) between detoxified alcoholic patients and
      healthy controls. Instead, the study revealed an inverse correlation between Kin
      (app) in left ventral striatum and alcohol craving scores. To resolve the influx
      and efflux phases of radiolabeled molecules, we independently estimated the
      unidirectional blood-brain FDOPA clearance rate (K) and the washout rate of
      [(18)F]fluorodopamine and its deaminated metabolites (k(loss)), and we also
      calculated the total distribution volume of decarboxylated metabolites and
      unmetabolized FDOPA as a steady-state index of the dopamine storage capacity
      (V(d)) in brain. The craving scores in the 12 alcoholics correlated positively
      with the rate of loss (k(loss)) in the left ventral striatum. We conclude that
      craving is most pronounced in the individuals with relatively rapid dopamine
      turnover in the left ventral striatum. The blood-brain clearance rate (K),
      corrected for subsequent loss of radiolabeled molecules from brain, was
      completely normal throughout the brain of the alcoholics, in whom the volume of
      distribution (V(d)) was found to be significantly lower in the left caudate
      nucleus. The magnitude of Vd in the left caudate head was reduced by 43% relative
      to the 16 controls, consistent with a 58% increase of k(loss). We interpret the
      findings as indicating that a trait for rapid dopamine turnover in the ventral
      striatum subserves craving and reward-dependence, leading to an acquired state of
      increased dopamine turnover in the dorsal striatum of detoxified alcoholic
      patients.

PMID- 24040112
TI  - Multicenter intestinal current measurements in rectal biopsies from CF and non-CF
      subjects to monitor CFTR function.
AB  - Intestinal current measurements (ICM) from rectal biopsies are a sensitive means
      to detect cystic fibrosis transmembrane conductance regulator (CFTR) function,
      but have not been optimized for multicenter use. We piloted multicenter standard
      operating procedures (SOPs) to detect CFTR activity by ICM and examined key
      questions for use in clinical trials. SOPs for ICM using human rectal biopsies
      were developed across three centers and used to characterize ion transport from
      non-CF and CF subjects (two severe CFTR mutations). All data were centrally
      evaluated by a blinded interpreter. SOPs were then used across four centers to
      examine the effect of cold storage on CFTR currents and compare CFTR currents in
      biopsies from one subject studied simultaneously either at two sites (24 hours
      post-biopsy) or when biopsies were obtained by either forceps or suction. Rectal
      biopsies from 44 non-CF and 17 CF subjects were analyzed. Mean differences
      (uA/cm(2); 95% confidence intervals) between CF and non-CF were
      forskolin/IBMX=102.6(128.0 to 81.1), carbachol=96.3(118.7 to 73.9),
      forskolin/IBMX+carbachol=200.9(243.1 to 158.6), and bumetanide=-44.6 (-33.7 to 
      55.6) (P<0.005, CF vs non-CF for all parameters). Receiver Operating
      Characteristic curves indicated that each parameter discriminated CF from non-CF
      subjects (area under the curve of 0.94-0.98). CFTR dependent currents following
      18-24 hours of cold storage for forskolin/IBMX, carbachol, and
      forskolin/IBMX+carbachol stimulation (n=17 non-CF subjects) were 44%, 47.5%, and
      47.3%, respectively of those in fresh biopsies. CFTR-dependent currents from
      biopsies studied after cold storage at two sites simultaneously demonstrated
      moderate correlation (n=14 non-CF subjects, Pearson correlation coefficients
      0.389, 0.484, and 0.533). Similar CFTR dependent currents were detected from
      fresh biopsies obtained by either forceps or suction (within-subject comparisons,
      n=22 biopsies from three non-CF subjects). Multicenter ICM is a feasible CFTR
      outcome measure that discriminates CF from non-CF ion transport, offers unique
      advantages over other CFTR bioassays, and warrants further development as a
      potential CFTR biomarker. 

PMID- 24040113
TI  - Mechanism of porcine liver xanthine oxidoreductase mediated N-oxide reduction of
      cyadox as revealed by docking and mutagenesis studies.
AB  - Xanthine oxidoreductase (XOR) is a cytoplasmic molybdenum-containing
      oxidoreductase, catalyzing both endogenous purines and exogenous compounds. It is
      suggested that XOR in porcine hepatocytes catalyzes the N-oxide reduction of
      quinoxaline 1,4-di-N-oxides (QdNOs). To elucidate the molecular mechanism
      underlying this metabolism, the cDNA of porcine XOR was cloned and heterologously
      expressed in Spodoptera frugiperda insect cells. The bovine XOR, showing sequence
      identity of 91% to porcine XOR, was employed as template for homology modeling.
      By docking cyadox, a representative compound of QdNOs, into porcine XOR model,
      eight amino acid residues, Gly47, Asn352, Ser360, Arg427, Asp430, Asp431, Ser1227
      and Lys1230, were located at distances of less than 4A to cyadox. Site-directed
      mutagenesis was performed to analyze their catalytic functions. Compared with
      wild type porcine XOR, G47A, S360P, D431A, S1227A, and K1230A displayed altered
      kinetic parameters in cyadox reduction, similarly to that in xanthine oxidation,
      indicating these mutations influenced electron-donating process of xanthine
      before subsequent electron transfer to cyadox to fulfill the N-oxide reduction.
      Differently, R427E and D430H, both located in the 424-434 loop, exhibited a much
      lower K(m) and a decreased V(max) respectively in cyadox reduction. Arg427 may be
      related to the substrate binding of porcine XOR to cyadox, and Asp430 is
      suggested to be involved in the transfer of electron to cyadox. This study
      initially reveals the possible catalytic mechanism of porcine XOR in cyadox
      metabolism, providing with novel insights into the structure-function
      relationship of XOR in the reduction of exogenous di-N-oxides.

PMID- 24040114
TI  - Negligible colon cancer risk from food-borne acrylamide exposure in male F344
      rats and nude (nu/nu) mice-bearing human colon tumor xenografts.
AB  - Acrylamide, a possible human carcinogen, is formed in certain carbohydrate-rich
      foods processed at high temperature. We evaluated if dietary acrylamide, at doses
      (0.5, 1.0 or 2.0 mg/kg diet) reflecting upper levels found in human foods,
      modulated colon tumorigenesis in two rodent models. Male F344 rats were
      randomized to receive diets without (control) or with acrylamide. 2-weeks later,
      rats in each group received two weekly subcutaneous injections of either
      azoxymethane (AOM) or saline, and were killed 20 weeks post-injections; colons
      were assessed for tumors. Male athymic nude (nu/nu) mice bearing HT-29 human
      colon adenocarcinoma cells-derived tumor xenografts received diets without
      (control) or with acrylamide; tumor growth was monitored and mice were killed 4
      weeks later. In the F344 rat study, no tumors were found in the colons of the
      saline-injected rats. However, the colon tumor incidence was 54.2% and 66.7% in
      the control and the 2 mg/kg acrylamide-treated AOM-injected groups, respectively.
      While tumor multiplicity was similar across all diet groups, tumor size and
      burden were higher in the 2 mg/kg acrylamide group compared to the AOM control.
      These results suggest that acrylamide by itself is not a "complete carcinogen",
      but acts as a "co-carcinogen" by exacerbating the effects of AOM. The nude mouse
      study indicated no differences in the growth of human colon tumor xenografts
      between acrylamide-treated and control mice, suggesting that acrylamide does not
      aid in the progression of established tumors. Hence, food-borne acrylamide at
      levels comparable to those found in human foods is neither an independent
      carcinogen nor a tumor promoter in the colon. However, our results characterize a
      potential hazard of acrylamide as a colon co-carcinogen in association with known
      and possibly other environmental tumor initiators/promoters. 

PMID- 24040115
TI  - Effectiveness and toxicities of intensity-modulated radiotherapy for patients
      with locally recurrent nasopharyngeal carcinoma.
AB  - PURPOSE: To analyze the effectiveness and toxicities in the re-irradiation of
      locally recurrent nasopharyngeal carcinoma (NPC) using intensity-modulated
      radiotherapy (IMRT). METHODS: This is a retrospective analysis of 54 NPC patients
      with local recurrence re-irradiated with IMRT. The re-staging for rT1, rT2, rT3,
      rT4 were 3 (5.6%), 8 (14.8%), 9 (16.7%), 34 (63%) respectively. The average dose
      to GTV was 69.95 Gy (49.8-76.58 Gy), the average BED(3Gy) was 116.8 Gy (83.5
      127.9 Gy). V95 was 96%, and D95 was 65.75 Gy. 33.3% of them received concurrent
      chemoradiotherapy. RESULTS: Median overall survival (OS) was 21 months (1-93
      mon). The 1-, 2-year local progression free survival (LPFS) rate was 84.5%, 64%
      and OS rate was 71.7%, 44.3%. Severe late adverse events (SLAE) occurred in 48.1%
      of patients, including 31.5% with ulcer or necrosis of the nasopharyngeal mucosa,
      20.4% with difficulty in feeding, 18.5% with temporal lobe necrosis, 11.1% with
      massive hemorrhage. 15.4% died of local regional progression, 5.8% died of
      distant metastasis, 25% died of SLAE, 9.6% died of both local regional
      progression and SLAE that could not be differentiated, 5.8% died of other medical
      complications. Concurrent chemoradiotherapy was the independent negative
      prognostic factors for LPFS; PTV>100 ml was a predictive factor of poor OS;
      patients with invasion of post-styloid space were at higher risk of SLAE.
      CONCLUSIONS: The present study demonstrated that IMRT with 70Gy was efficient for
      local tumor control. However, we observed a high frequency of serious late
      complications. More optimized combination treatment and patient selection are
      required to achieve excellent local control without significant late morbidities
      in locally recurrent NPC.

PMID- 24040116
TI  - Internal consistency, test-retest reliability and measurement error of the self
      report version of the social skills rating system in a sample of Australian
      adolescents.
AB  - The social skills rating system (SSRS) is used to assess social skills and
      competence in children and adolescents. While its characteristics based on United
      States samples (US) are published, corresponding Australian figures are
      unavailable. Using a 4-week retest design, we examined the internal consistency,
      retest reliability and measurement error (ME) of the SSRS secondary student form
      (SSF) in a sample of Year 7 students (N = 187), from five randomly selected
      public schools in Perth, western Australia. Internal consistency (IC) of the
      total scale and most subscale scores (except empathy) on the frequency rating
      scale was adequate to permit independent use. On the importance rating scale,
      most IC estimates for girls fell below the benchmark. Test-retest estimates of
      the total scale and subscales were insufficient to permit reliable use. ME of the
      total scale score (frequency rating) for boys was equivalent to the US estimate,
      while that for girls was lower than the US error. ME of the total scale score
      (importance rating) was larger than the error using the frequency rating scale.
      The study finding supports the idea of using multiple informants (e.g. teacher
      and parent reports), not just student as recommended in the manual. Future
      research needs to substantiate the clinical meaningfulness of the MEs calculated
      in this study by corroborating them against the respective Minimum Clinically
      Important Difference (MCID). 

PMID- 24040117
TI  - Enterohemorrhagic Escherichia coli as causes of hemolytic uremic syndrome in the
      Czech Republic.
AB  - BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC) cause diarrhea-associated
      hemolytic uremic syndrome (D+ HUS) worldwide, but no systematic study of EHEC as
      the causative agents of HUS was performed in the Czech Republic. We analyzed
      stools of all patients with D+ HUS in the Czech Republic between 1998 and 2012
      for evidence of EHEC infection. We determined virulence profiles, phenotypes,
      antimicrobial susceptibilities and phylogeny of the EHEC isolates.
      METHODOLOGY/PRINCIPAL FINDINGS: Virulence loci were identified using PCR,
      phenotypes and antimicrobial susceptibilities were determined using standard
      procedures, and phylogeny was assessed using multilocus sequence typing. During
      the 15-year period, EHEC were isolated from stools of 39 (69.4%) of 56 patients.
      The strains belonged to serotypes [fliC types] O157:H7/NM[fliC(H7)] (50% of which
      were sorbitol-fermenting; SF), O26:H11/NM[fliC(H11)], O55:NM[fliC(H7)],
      O111:NM[fliC(H8)], O145:H28[fliC(H28)], O172:NM[fliC(H25)], and
      Orough:NM[fliC(H250]. O26:H11/NM[fliC(H11)] was the most common serotype
      associated with HUS (41% isolates). Five stx genotypes were identified, the most
      frequent being stx(2a) (71.1% isolates). Most strains contained EHEC-hlyA
      encoding EHEC hemolysin, and a subset (all SF O157:NM and one O157:H7) harbored
      cdt-V encoding cytolethal distending toxin. espPalpha encoding serine protease
      EspPalpha was found in EHEC O157:H7, O26:H11/NM, and O145:H28, whereas O172:NM
      and Orough:NM strains contained espPgamma. All isolates contained eae encoding
      adhesin intimin, which belonged to subtypes beta (O26), gamma (O55, O145, O157),
      gamma2/theta (O111), and epsilon (O172, Orough). Loci encoding other adhesins
      (efa1, lpfA(O26), lpfA(O157OI-141), lpfA(O157OI-154), iha) were usually
      associated with particular serotypes. Phylogenetic analysis demonstrated nine
      sequence types (STs) which correlated with serotypes. Of these, two STs (ST660
      and ST1595) were not found in HUS-associated EHEC before.
      CONCLUSIONS/SIGNIFICANCE: EHEC strains, including O157:H7 and non-O157:H7, are
      frequent causes of D+ HUS in the Czech Republic. Identification of unusual EHEC
      serotypes/STs causing HUS calls for establishment of an European collection of
      HUS-associated EHEC, enabling to study properties and evolution of these
      important pathogens.

PMID- 24040118
TI  - Sex-related differences of cortical thickness in patients with chronic abdominal
      pain.
AB  - BACKGROUND & AIMS: Regional reductions in gray matter (GM) have been reported in
      several chronic somatic and visceral pain conditions, including irritable bowel
      syndrome (IBS) and chronic pancreatitis. Reported GM reductions include insular
      and anterior cingulate cortices, even though subregions are generally not
      specified. The majority of published studies suffer from limited sample size,
      heterogeneity of populations, and lack of analyses for sex differences. We aimed
      to characterize regional changes in cortical thickness (CT) in a large number of
      well phenotyped IBS patients, taking into account the role of sex related
      differences. METHODS: Cortical GM thickness was determined in 266 subjects (90
      IBS [70 predominantly premenopausal female] and 176 healthy controls (HC) [155
      predominantly premenopausal female]) using the Laboratory of Neuro Imaging (LONI)
      Pipeline. A combined region of interest (ROI) and whole brain approach was used
      to detect any sub-regional and vertex-level differences after removing effects of
      age and total GM volume. Correlation analyses were performed on behavioral data.
      RESULTS: While IBS as a group did not show significant differences in CT compared
      to HCs, sex related differences were observed both within the IBS and the HC
      groups. When female IBS patients were compared to female HCs, whole brain
      analysis showed significant CT increase in somatosensory and primary motor
      cortex, as well as CT decrease in bilateral subgenual anterior cingulate cortex
      (sgACC). The ROI analysis showed significant regional CT decrease in bilateral
      subregions of insular cortex, while CT decrease in cingulate was limited to left
      sgACC, accounting for the effect of age and GM volume. Several measures of IBS
      symptom severity showed significant correlation with CT changes in female IBS
      patients. CONCLUSIONS: Significant, sex related differences in CT are present in
      both HCs and in IBS patients. The biphasic neuroplastic changes in female IBS
      patients are related to symptom severity.

PMID- 24040119
TI  - A toxicogenomic approach for the prediction of murine hepatocarcinogenesis using
      ensemble feature selection.
AB  - The current strategy for identifying the carcinogenicity of drugs involves the 2
      year bioassay in male and female rats and mice. As this assay is cost-intensive
      and time-consuming there is a high interest in developing approaches for the
      screening and prioritization of drug candidates in preclinical safety
      evaluations. Predictive models based on toxicogenomics investigations after short
      term exposure have shown their potential for assessing the carcinogenic risk. In
      this study, we investigated a novel method for the evaluation of toxicogenomics
      data based on ensemble feature selection in conjunction with bootstrapping for
      the purpose to derive reproducible and characteristic multi-gene signatures. This
      method was evaluated on a microarray dataset containing global gene expression
      data from liver samples of both male and female mice. The dataset was generated
      by the IMI MARCAR consortium and included gene expression profiles of genotoxic
      and nongenotoxic hepatocarcinogens obtained after treatment of CD-1 mice for 3 or
      14 days. We developed predictive models based on gene expression data of both
      sexes and the models were employed for predicting the carcinogenic class of
      diverse compounds. Comparing the predictivity of our multi-gene signatures
      against signatures from literature, we demonstrated that by incorporating our
      gene sets as features slightly higher accuracy is on average achieved by a
      representative set of state-of-the art supervised learning methods. The
      constructed models were also used for the classification of Cyproterone acetate
      (CPA), Wy-14643 (WY) and Thioacetamid (TAA), whose primary mechanism of
      carcinogenicity is controversially discussed. Based on the extracted mouse liver
      gene expression patterns, CPA would be predicted as a nongenotoxic compound. In
      contrast, both WY and TAA would be classified as genotoxic mouse
      hepatocarcinogens. 

PMID- 24040120
TI  - DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent
      mechanisms in pancreatic cancer.
AB  - Stem cell pluripotency, angiogenesis and epithelial-mesenchymal transition (EMT)
      have been shown to be significantly upregulated in pancreatic ductal
      adenocarcinoma (PDAC) and many other aggressive cancers. The dysregulation of
      these processes is believed to play key roles in tumor initiation, progression,
      and metastasis, and is contributory to PDAC being the fourth leading cause of
      cancer-related deaths in the US. The tumor suppressor miRNA miR-145 downregulates
      critical pluripotency factors and oncogenes and results in repressed metastatic
      potential in PDAC. Additionally, the miR-200 family regulates several angiogenic
      factors which have been linked to metastasis in many solid tumors. We have
      previously demonstrated that downregulation of DCLK1 can upregulate critical
      miRNAs in both in vitro and in vivo cancer models and results in downregulation
      of c-MYC, KRAS, NOTCH1 and EMT-related transcription factors. A recent report has
      also shown that Dclk1 can distinguish between normal and tumor stem cells in Apc
      (min/+) mice and that ablation of Dclk1(+) cells resulted in regression of
      intestinal polyps without affecting homeostasis. Here we demonstrate that the
      knockdown of DCLK1 using poly(lactide-co-glycolide)-encapsulated-DCLK1-siRNA
      results in AsPC1 tumor growth arrest. Examination of xenograft tumors revealed,
      (a) increased miR-145 which results in decreased pluripotency maintenance factors
      OCT4, SOX2, NANOG, KLF4 as well as KRAS and RREB1; (b) increased let-7a which
      results in decreased pluripotency factor LIN28B; and (c) increased miR-200 which
      results in decreased VEGFR1, VEGFR2 and EMT-related transcription factors ZEB1,
      ZEB2, SNAIL and SLUG. Specificity of DCLK1 post-transcriptional regulation of the
      downstream targets of miR-145, miR-200 and let-7a was accomplished utilizing a
      luciferase-based reporter assay. We conclude that DCLK1 plays a significant
      master regulatory role in pancreatic tumorigenesis through the regulation of
      multiple tumor suppressor miRNAs and their downstream pro-tumorigenic pathways.
      This novel concept of targeting DCLK1 alone has several advantages over targeting
      single pathway or miRNA-based therapies for PDAC. 

PMID- 24040121
TI  - Concomitant targeting of multiple key transcription factors effectively disrupts
      cancer stem cells enriched in side population of human pancreatic cancer cells.
AB  - BACKGROUND: A major challenge in the treatment of pancreatic ductal
      adenocarcinoma is the failure of chemotherapy, which is likely due to the
      presence of the cancer stem cells (CSCs). OBJECTIVE: To identify side population
      (SP) cells and characterize s-like properties in human pancreatic cancer cell
      lines (h-PCCLs) and to exploit the efficacy of concomitant targeting of multiple
      key transcription factors governing the stemness of pancreatic CSCs in
      suppressing CSC-like phenotypes. METHODS: Flow cytometry and Hoechst 33342 DNA
      binding dye efflux assay were used to sort SP and non-SP (NSP) cells from three h
      PCCLs: PANC-1, SW1990, and BxPc-3. The self-renewal ability, invasiveness,
      migration and drug resistance of SP cells were evaluated. Expression of CSC
      marker genes was analyzed. Tumorigenicity was assessed using a xenograft model in
      nude mice. Effects of a complex decoy oligonucleotide (cdODN-SCO) designed to
      simultaneously targeting Sox2, Oct4 and c-Myc were assessed. RESULTS: CSCs were
      enriched in the side proportion (SP) cells contained in the h-PCCLs and they
      possessed aggressive growth, invasion, migration and drug-resistance properties,
      compared with NSP cells. SP cells overexpressed stem cell markers CD133 and
      ALDH1, pluripotency maintaining factors Nanog, Sox2 and Oct4, oncogenic
      transcription factor c-Myc, signaling molecule Notch1, and drug resistant gene
      ABCG2. Moreover, SP cells consistently demonstrated significantly greater
      tumorigenicity than NSP cells in xenograft model of nude mice. CdODN-SOC
      efficiently suppressed all CSC properties and phenotypes, and minimized the
      tumorigenic capability of the SP cells and the resistance to chemotherapy. By
      comparison, the negative control failed to do so. CONCLUSION: The findings
      indicate that targeting the key genes conferring the stemness of CSCs can
      efficiently eliminate CSC-like phenotypes, and thus may be considered a new
      approach for cancer therapy. Specifically, the present study establishes the
      combination of Sox2/Oct4/c-Myc targeting as a potential anti-pancreatic cancer
      agent worthy of further studies in preclinical settings.

PMID- 24040122
TI  - Transimulation - protein biosynthesis web service.
AB  - Although translation is the key step during gene expression, it remains poorly
      characterized at the level of individual genes. For this reason, we developed
      Transimulation - a web service measuring translational activity of genes in three
      model organisms: Escherichia coli, Saccharomyces cerevisiae and Homo sapiens. The
      calculations are based on our previous computational model of translation and
      experimental data sets. Transimulation quantifies mean translation initiation and
      elongation time (expressed in SI units), and the number of proteins produced per
      transcript. It also approximates the number of ribosomes that typically occupy a
      transcript during translation, and simulates their propagation. The simulation of
      ribosomes' movement is interactive and allows modifying the coding sequence on
      the fly. It also enables uploading any coding sequence and simulating its
      translation in one of three model organisms. In such a case, ribosomes propagate
      according to mean codon elongation times of the host organism, which may prove
      useful for heterologous expression. Transimulation was used to examine
      evolutionary conservation of translational parameters of orthologous genes.
      Transimulation may be accessed at http://nexus.ibb.waw.pl/Transimulation
      (requires Java version 1.7 or higher). Its manual and source code, distributed
      under the GPL-2.0 license, is freely available at the website. 

PMID- 24040123
TI  - Dissemination and characterization of plasmids carrying oqxAB-bla CTX-M genes in
      Escherichia coli isolates from food-producing animals.
AB  - BACKGROUND: The association of PMQR and ESBLs in negative-bacteria isolates has
      been of great concern. The present study was performed to investigate the
      prevalence of co-transferability of oqxAB and bla CTX-M genes among the 696
      Escherichia coli (E. coli) isolates from food-producing animals in South China,
      and to characterize these plasmids. METHODS: The ESBL-encoding genes (bla(CTX-M),
      bla(TEM) and bla(SHV)), and PMQR (qnrA, qnrB, qnrS, qnrC, qnrD, aac(6')-Ib-cr,
      qepA, and oqxAB) of these 696 isolates were determined by PCR and sequenced
      directionally. Conjugation, S1 nuclease pulsed-field gel electrophoresis (PFGE)
      and Southern blotting experiments were performed to investigate the co
      transferability and location of oqxAB and bla(CTX-M). The EcoRI digestion
      profiles of the plasmids with oqxAB-bla(CTX-M) were also analyzed. The clonal
      relatedness was investigated by PFGE. RESULTS: Of the 696 isolates, 429 harbored
      at least one PMQR gene, with oqxAB (328) being the most common type; 191 carried
      bla(CTX-M), with bla(CTX-M-14) the most common. We observed a significant higher
      prevalence of bla(CTX-M) among the oqxAB-positive isolates (38.7%) than that
      (17.4%) in the oqxAB-negative isolates. Co-transferability of oqxAB and bla(CTX
      M) was found in 18 of the 127 isolates carrying oqxAB-bla(CTX-M). These two genes
      were located on the same plasmid in all the 18 isolates, with floR being on these
      plasmids in 13 isolates. The co-dissemination of these genes was mainly mediated
      by F33:A-: B- and HI2 plasmids with highly similar EcoRI digestion profiles.
      Diverse PFGE patterns indicated the high prevalence of oqxAB was not caused by
      clonal dissemination. CONCLUSION: bla(CTX-M) was highly prevalent among the oqxAB
      positive isolates. The co-dissemination of oqxAB-bla(CTX-M) genes in E. coli
      isolates from food-producing animals is mediated mainly by similar F33:A-: B- and
      HI2 plasmids. This is the first report of the co-existence of oqxAB, bla(CTX-M),
      and floR on the same plasmids in E. coli.

PMID- 24040124
TI  - Analgesic effect of acupuncture is mediated via inhibition of JNK activation in
      astrocytes after spinal cord injury.
AB  - Acupuncture (AP) has been used worldwide to relieve pain. However, the mechanism
      of action of AP is poorly understood. Here, we found that AP relieved neuropathic
      pain (NP) by inhibiting Jun-N-terminal kinase (JNK) activation in astrocytes
      after spinal cord injury (SCI). After contusion injury which induces the below
      level (L4-L5) NP, Shuigou (GV26) and Yanglingquan (GB34) acupoints were applied.
      At 31 d after injury, both mechanical allodynia and thermal hyperalgesia were
      significantly alleviated by AP applied at GV26 and GB34. Immunocytochemistry
      revealed that JNK activation was mainly observed in astrocytes after injury. AP
      inhibited JNK activation in astrocytes at L4-L5 level of spinal cord. The level
      of p-c-Jun known, a downstream molecule of JNK, was also decreased by AP. In
      addition, SCI-induced GFAP expression, a marker for astrocytes, was decreased by
      AP as compared to control groups. Especially, the number of hypertrophic,
      activated astrocytes in laminae I-II of dorsal horn at L4-5 was markedly
      decreased by AP treatment when compared with vehicle and simulated AP-treated
      groups. When animals treated with SP600125, a specific JNK inhibitor, after SCI,
      both mechanical allodynia and thermal hyperalgesia were significantly attenuated
      by the inhibitor, suggesting that JNK activation is likely involved in SCI
      induced NP. Also, the expression of chemokines which is known to be mediated
      through JNK pathway was significantly decreased by AP and SP600125 treatment.
      Therefore, our results indicate that analgesic effect of AP is mediated in part
      by inhibiting JNK activation in astrocytes after SCI. 

PMID- 24040125
TI  - Retinoic acid metabolic genes, meiosis, and gonadal sex differentiation in
      zebrafish.
AB  - To help understand the elusive mechanisms of zebrafish sex determination, we
      studied the genetic machinery regulating production and breakdown of retinoic
      acid (RA) during the onset of meiosis in gonadogenesis. Results uncovered
      unexpected mechanistic differences between zebrafish and mammals. Conserved
      synteny and expression analyses revealed that cyp26a1 in zebrafish and its
      paralog Cyp26b1 in tetrapods independently became the primary genes encoding
      enzymes available for gonadal RA-degradation, showing lineage-specific
      subfunctionalization of vertebrate genome duplication (VGD) paralogs. Experiments
      showed that zebrafish express aldh1a2, which encodes an RA-synthesizing enzyme,
      in the gonad rather than in the mesonephros as in mouse. Germ cells in
      bipotential gonads of all zebrafish analyzed were labeled by the early meiotic
      marker sycp3, suggesting that in zebrafish, the onset of meiosis is not sexually
      dimorphic as it is in mouse and is independent of Stra8, which is required in
      mouse but was lost in teleosts. Analysis of dead-end knockdown zebrafish depleted
      of germ cells revealed the germ cell-independent onset and maintenance of gonadal
      aldh1a2 and cyp26a1 expression. After meiosis initiated, somatic cell expression
      of cyp26a1 became sexually dimorphic: up-regulated in testes but not ovaries.
      Meiotic germ cells expressing the synaptonemal complex gene sycp3 occupied
      islands of somatic cells that lacked cyp26a1 expression, as predicted by the
      hypothesis that Cyp26a1 acts as a meiosis-inhibiting factor. Consistent with this
      hypothesis, females up-regulated cyp26a1 in oocytes that entered prophase-I
      meiotic arrest, and down-regulated cyp26a1 in oocytes resuming meiosis. Co
      expression of cyp26a1 and the pluripotent germ cell stem cell marker pou5f1(oct4)
      in meiotically arrested oocytes was consistent with roles in mouse to promote
      germ cell survival and to prevent apoptosis, mechanisms that are central for
      tipping the sexual fate of gonads towards the female pathway in zebrafish. 

PMID- 24040126
TI  - Elevated plasma soluble Sema4D/CD100 levels are associated with disease severity
      in patients of hemorrhagic fever with renal syndrome.
AB  - BACKGROUND: Hantaan virus (HTNV) could cause a severe lethal hemorrhagic fever
      with renal syndrome (HFRS) in humans. Despite a limited understanding of the
      pathogenesis of HFRS, the importance of host-related immune responses in the
      pathogenesis of HFRS has been widely recognized. CD100/Sema4D has been
      demonstrated to play an important role in physiological and pathological immune
      responses, but the functional role of CD100 in infectious diseases has only been
      inadequately reported. The aim of this study was to investigate the pathological
      significance of CD100 in patients after HTNV infection. METHODOLOGY/PRINCIPAL
      FINDINGS: Blood samples were collected from 99 hospitalized patients in Tangdu
      Hospital and 27 health controls. The level of soluble CD100 (sCD100) in plasma
      were quantified by ELISA and the relationship between sCD100 and the disease
      course or severity were analyzed. The expressions of membrane CD100 on various
      subpopulations of peripheral blood mononuclear cell (PBMC) were analyzed by flow
      cytometry. The results showed that sCD100 level in acute phase of HFRS was
      significantly higher in patients than that in healthy controls (P<0.0001) and the
      sCD100 level declined in convalescent phase. Multivariate model analysis showed
      that platelet count, white blood cell count, serum creatinine level and blood
      urea nitrogen level were associated with sCD100 levels and contributed
      independently to the elevated sCD100 levels. The expression of membrane CD100 on
      PBMCs decreased in the acute phase of HFRS patients compared with that of the
      normal controls and recovered in the convalescent phase. CONCLUSIONS: We reported
      the elevated level of plasma sCD100 in HFRS patients and the elevated level might
      be a result from the shedding of membrane CD100 on PBMC. The elevated level of
      sCD100 was associated with disease severity, suggesting that sCD100 might be a
      cause or a consequence of progression of HFRS. The underlying mechanisms should
      be explored further.

PMID- 24040127
TI  - Reduced number and morphofunctional change of alveolar macrophages in MafB gene
      targeted mice.
AB  - Alveolar macrophages (AMs) play an important role in the pathogenesis of chronic
      obstructive pulmonary disease (COPD). We previously demonstrated that the
      transcription factor, MafB, increased in the AMs of mice exposed to cigarette
      smoke, and in those of human patients with COPD. The aim of this study was to
      evaluate the role of MafB in AMs using newly established transgenic (TG) mice
      that specifically express dominant negative (DN) MafB in macrophages under the
      control of macrophage scavenger receptor (MSR) enhancer-promoter. We performed
      cell differential analyses in bronchoalveolar lavage cells, morphological
      analyses with electron microscopy, and flow cytometry-based analyses of surface
      markers and a phagocytic capacity assay in macrophages. AM number in the TG mice
      was significantly decreased compared with wild-type (WT) mice. Morphologically,
      the high electron density area in the nucleus increased, the shape of pseudopods
      on the AMs was altered, and actin filament was less localized in the pseudopods
      of AMs of TG mice, compared with WT mice. The expression of surface markers,
      F4/80 and CD11b, on peritoneal macrophages in TG mice was reduced compared with
      WT mice, while those on AMs remained unchanged. Phagocytic capacity was decreased
      in AMs from TG mice, compared with WT mice. In conclusion, MafB regulates the
      phenotype of macrophages with respect to the number of alveolar macrophages, the
      nuclear compartment, cellular shape, surface marker expression, and phagocytic
      function. MSR-DN MafB TG mice may present a useful model to clarify the precise
      role of MafB in macrophages. 

PMID- 24040128
TI  - Can hippocampal neurites and growth cones climb over obstacles?
AB  - Guidance molecules, such as Sema3A or Netrin-1, can induce growth cone (GC)
      repulsion or attraction in the presence of a flat surface, but very little is
      known of the action of guidance molecules in the presence of obstacles. Therefore
      we combined chemical and mechanical cues by applying a steady Netrin-1 stream to
      the GCs of dissociated hippocampal neurons plated on polydimethylsiloxane (PDMS)
      surfaces patterned with lines 2 um wide, with 4 um period and with a height
      varying from 100 to 600 nm. GC turning experiments performed 24 hours after
      plating showed that filopodia crawl over these lines within minutes. These
      filopodia do not show staining for the adhesion marker Paxillin. GCs and neurites
      crawl over lines 100 nm high, but less frequently and on a longer time scale over
      lines higher than 300 nm; neurites never crawl over lines 600 nm high. When
      neurons are grown for 3 days over patterned surfaces, also neurites can cross
      lines 300 nm and 600 nm high, grow parallel to and on top of these lines and
      express Paxillin. Axons - selectively stained with SMI 312 - do not differ from
      dendrites in their ability to cross these lines. Our results show that highly
      motile structures such as filopodia climb over high obstacle in response to
      chemical cues, but larger neuronal structures are less prompt and require hours
      or days to climb similar obstacles. 

PMID- 24040129
TI  - Estimating potential infection transmission routes in hospital wards using
      wearable proximity sensors.
AB  - BACKGROUND: Contacts between patients, patients and health care workers (HCWs)
      and among HCWs represent one of the important routes of transmission of hospital
      acquired infections (HAI). A detailed description and quantification of contacts
      in hospitals provides key information for HAIs epidemiology and for the design
      and validation of control measures. METHODS AND FINDINGS: We used wearable
      sensors to detect close-range interactions ("contacts") between individuals in
      the geriatric unit of a university hospital. Contact events were measured with a
      spatial resolution of about 1.5 meters and a temporal resolution of 20 seconds.
      The study included 46 HCWs and 29 patients and lasted for 4 days and 4 nights.
      14,037 contacts were recorded overall, 94.1% of which during daytime. The number
      and duration of contacts varied between mornings, afternoons and nights, and
      contact matrices describing the mixing patterns between HCW and patients were
      built for each time period. Contact patterns were qualitatively similar from one
      day to the next. 38% of the contacts occurred between pairs of HCWs and 6 HCWs
      accounted for 42% of all the contacts including at least one patient, suggesting
      a population of individuals who could potentially act as super-spreaders.
      CONCLUSIONS: Wearable sensors represent a novel tool for the measurement of
      contact patterns in hospitals. The collected data can provide information on
      important aspects that impact the spreading patterns of infectious diseases, such
      as the strong heterogeneity of contact numbers and durations across individuals,
      the variability in the number of contacts during a day, and the fraction of
      repeated contacts across days. This variability is however associated with a
      marked statistical stability of contact and mixing patterns across days. Our
      results highlight the need for such measurement efforts in order to correctly
      inform mathematical models of HAIs and use them to inform the design and
      evaluation of prevention strategies.

PMID- 24040130
TI  - NO3-/H+ antiport in the tonoplast of cucumber root cells is stimulated by nitrate
      supply: evidence for a reversible nitrate-induced phosphorylation of vacuolar NO3
      /H+ antiport.
AB  - Studies in the last few years have shed light on the process of nitrate
      accumulation within plant cells, achieving molecular identification and partial
      characterization of the genes and proteins involved in this process. However,
      contrary to the plasma membrane-localized nitrate transport activities, the
      kinetics of active nitrate influx into the vacuole and its adaptation to external
      nitrate availability remain poorly understood. In this work, we have investigated
      the activity and regulation of the tonoplast-localized H(+)/NO3(-) antiport in
      cucumber roots in response to N starvation and NO3(-) induction. The time course
      of nitrate availability strongly influenced H(+)/NO3(-) antiport activity at the
      tonoplast of root cells. However, under N starvation active nitrate accumulation
      within the vacuole still occurred. Hence, either a constitutive H(+)-coupled
      transport system specific for nitrate operates at the tonoplast, or nitrate uses
      another transport protein of broader specificity to different anions to enter the
      vacuole via a proton-dependent process. H(+)/NO3(-) antiport in cucumber was
      significantly stimulated in NO3(-)-induced plants that were supplied with nitrate
      for 24 hours following 6-day-long N starvation. The cytosolic fraction isolated
      from the roots of NO3(-)-induced plants significantly stimulated H(+)/NO3(-)
      antiport in tonoplast membranes isolated from cucumbers growing on nitrate. The
      stimulatory effect of the cytosolic fraction was completely abolished by EGTA and
      the protein kinase inhibitor staurosporine and slightly enhanced by the
      phosphatase inhibitors okadaic acid and cantharidin. Hence, we conclude that
      stimulation of H(+)/NO3(-) antiport at the tonoplast of cucumber roots in
      response to nitrate provision may occur through the phosphorylation of a membrane
      antiporter involving Ca-dependent, staurosporine-sensitive protein kinase.

PMID- 24040131
TI  - An association between initiation of selective serotonin reuptake inhibitors and
      suicide - a nationwide register-based case-crossover study.
AB  - BACKGROUND: Treatment with selective serotonin reuptake inhibitors (SSRI) is one
      of the most common treatments for depression. It is however not clear whether or
      not there is an increased short-term suicide risk during initiation with SSRI.
      METHODS: A register-based nationwide case-crossover study including 5,866
      suicides, 1,698 women and 4,168 men, from the Death Register 2007-2010 in Sweden.
      SSRI initiation was defined as a dispensed prescription of SSRI within 28 days
      prior to the date of suicide with no previous dispensed prescription of SSRI
      within 4 months prior that prescription. The control period took place one year
      earlier. Odds ratio (OR) was estimated using conditional logistic regression.
      RESULT: During the 28 day period prior to suicide 48 women and 138 men were
      exposed to SSRI initiation (while not being exposed in the control period) and 22
      women and 43 men were exposed in the control period (while not being exposed in
      the case period). The OR for suicide after initiation with SSRI was 2.7 (95% CI:
      1.6-44) for women, and 4.3 (95% CI: 3.0-6.1) for men. The highest OR was found 8
      11 days after initiation with SSRI 9.7 (95% CI: 3.0-31.7) for women and men
      combined. CONCLUSION: The main limitation in this study is confounding by
      indication, but the descriptive question is however not confounded by indication.
      Together with plausible biological mechanisms and previous clinical and
      epidemiological observations our findings, linking initiation of SSRI to
      increased short-term suicide risk, deserve further attention specifically in the
      clinical setting.

PMID- 24040132
TI  - Chest radiograph findings and time to culture conversion in patients with
      multidrug-resistant tuberculosis and HIV in Tugela Ferry, South Africa.
AB  - BACKGROUND: The majority of patients with multidrug-resistant tuberculosis (MDR
      TB) in South Africa are co-infected with HIV, but the radiographic features of
      MDR-TB and their relationship with time to sputum culture conversion in the
      antiretroviral therapy era have not been described. METHODS: We reviewed baseline
      chest radiographs for 56 patients with MDR-TB from a rural area of South Africa.
      We analyzed the association of cavities, consolidation, pleural effusion and
      hilar lymphadenopathy with time to sputum culture conversion, adjusting for HIV
      status, baseline sputum smear and CD4 count. RESULTS: Of the 56 subjects, 49
      (88%) were HIV-positive, with a median CD4 count of 136 cells/mm(3) (IQR 65-249).
      Thirty-two (57%) patients were sputum smear positive. Twenty-two (39%) patients
      had a cavity and 37 (66%) patients had consolidations. Cavitary disease and
      consolidations were each associated with longer time to culture conversion on
      bivariate analysis but not after adjusting for sputum smear status (aORs 1.79
      [0.94-3.42] and 1.09 [0.67-1.78], respectively). Positive baseline sputum smear
      remained independently associated with longer time to conversion (aOR 3.45 [1.39
      8.59]). We found no association between pleural effusion or hilar lymphadenopathy
      and time to conversion. Seventy-nine percent of patients were cured at the end of
      treatment. CONCLUSIONS: Despite high rates of HIV co-infection and advanced
      immunodeficiency, the majority of patients had severe pathology on baseline chest
      radiograph. Nevertheless, culture conversion rates were high and treatment
      outcomes were favorable. Cavitation and consolidation do not appear to have an
      independent association with time to culture conversion beyond that of baseline
      sputum smear status.

PMID- 24040133
TI  - High prevalence of human T-lymphotropic virus infection in indigenous women from
      the peruvian Amazon.
AB  - BACKGROUND: In an earlier study, we detected an association between human T-cell
      lymphotropic virus (HTLV) infection and cervical human papillomavirus (HPV) in
      indigenous Amazonian Peruvian women of the Shipibo-Konibo ethnic group. As both
      HTLV and HPV can be transmitted sexually, we now report a population-based study
      examining the prevalence and risk factors for HTLV-1 and HTLV-2 infection in this
      population. METHODS: Between July and December 2010, we conducted a comprehensive
      screening for HTLV among Shipibo-Konibo women 15 to 39 years of age living in two
      communities located in Lima and in 17 communities located within four hours by
      car or boat from the Amazonian city of Pucallpa in Peru. RESULTS: We screened
      1,253 Shipibo-Konibo women for HTLV infection 74 (5.9%) tested positive for HTLV
      1, 47 (3.8%) for HTLV-2 infection, and 4 (0.3%) had indeterminate results. In the
      multivariate analysis, factors associated with HTLV-1 infection included: older
      age (Prevalence Ratio (PR): 1.04, 95% CI 1.00-1.08), primary education or less
      (PR: 2.01, 95% CI: 1.25-3.24), younger or same age most recent sex partner (PR:
      1.66, 95% CI: 1.00-2.74), and having a most recent sex partner who worked at a
      logging camp (PR: 1.73, 95% CI: 1.09-2.75). The only factor associated with HTLV
      2 infection was older age (PR: 1.08, 95% CI: 1.03-1.12). CONCLUSION: HTLV
      infection is endemic among Shipibo-Konibo women. Two characteristics of the
      sexual partner (younger age and labor history) were associated with infection in
      women. These results suggest the need for implementation of both HTLV screening
      during the antenatal healthcare visits of Shipibo-Konibo women, and counseling
      about the risk of HTLV transmission through prolonged breastfeeding in infected
      women. We also recommend the implementation of prevention programs to reduce
      sexual transmission of these viruses.

PMID- 24040134
TI  - Changes in tetrodotoxin-resistant C-fibre activity during fatiguing isometric
      contractions in the rat.
AB  - It is by now well established that tetrodotoxin-resistant (TTX-R) afferent fibres
      from muscle in the rat exhibit a multisensitive profile, including nociception.
      TTX-R afferent fibres play an important role in motor control, via spinal and
      supraspinal loops, but their activation and function during muscle exercise and
      fatigue are still unknown. Therefore, the specific effect of isometric fatiguing
      muscle contraction on the responsiveness of TTX-R C-fibres has been investigated
      in this study. To quantify the TTX-R afferent input we recorded the cord dorsum
      potential (CDP), which is the result of the electrical fields set up within the
      spinal cord by the depolarisation of the interneurons located in the dorsal horn,
      activated by an incoming volley of TTX-R muscle afferents. The changes in TTX-R
      CDP size before, during and after fatiguing electrical stimulation of the
      gastrocnemius-soleus (GS) muscle have been taken as a measure of TTX-R C-unit
      activation. At the end of the fatiguing protocol, following an exponential drop
      in force, TTX-R CDP area decreased in the majority of trials (9/14) to 0.75 +/-
      0.03% (mean +/- SEM) of the pre-fatigue value. Recovery to the control size of
      the TTX-R CDP was incomplete after 10 min. Furthermore, fatiguing trials could
      sensitise a fraction of the TTX-R C-fibres responding to muscle pinch. The
      results suggest a long-lasting activation of the TTX-R muscle afferents after
      fatiguing stimulation. The role of this behaviour in chronic muscle fatigue in
      connection with pain development is discussed. Accumulation of metabolites
      released into the interstitium during fatiguing stimulation might be one of the
      reasons underlying the C-fibres' long-lasting activation.

PMID- 24040135
TI  - Additional sex combs-like 2 is required for polycomb repressive complex 2 binding
      at select targets.
AB  - Polycomb Group (PcG) proteins are epigenetic repressors of gene expression. The
      Drosophila Additional sex combs (Asx) gene and its mammalian homologs exhibit PcG
      function in genetic assays; however, the mechanism by which Asx family proteins
      mediate gene repression is not well understood. ASXL2, one of three mammalian
      homologs for Asx, is highly expressed in the mammalian heart and is required for
      the maintenance of cardiac function. We have previously shown that Asxl2
      deficiency results in a reduction in the bulk level of histone H3 lysine 27
      trimethylation (H3K27me3), a repressive mark generated by the Polycomb Repressive
      Complex 2 (PRC2). Here we identify several ASXL2 target genes in the heart and
      investigate the mechanism by which ASXL2 facilitates their repression. We show
      that the Asxl2-deficient heart is defective in converting H3K27me2 to H3K27me3
      and in removing ubiquitin from mono-ubiquitinated histone H2A. ASXL2 and PRC2
      interact in the adult heart and co-localize to target promoters. ASXL2 is
      required for the binding of PRC2 and for the enrichment of H3K27me3 at target
      promoters. These results add a new perspective to our understanding of the
      mechanisms that regulate PcG activity and gene repression. 

PMID- 24040136
TI  - Comparative sequence and structure analysis reveals the conservation and
      diversity of nucleotide positions and their associated tertiary interactions in
      the riboswitches.
AB  - The tertiary motifs in complex RNA molecules play vital roles to either stabilize
      the formation of RNA 3D structure or to provide important biological
      functionality to the molecule. In order to better understand the roles of these
      tertiary motifs in riboswitches, we examined 11 representative riboswitch PDB
      structures for potential agreement of both motif occurrences and conservations. A
      total of 61 unique tertiary interactions were found in the reference structures.
      In addition to the expected common A-minor motifs and base-triples mainly
      involved in linking distant regions the riboswitch structures three highly
      conserved variants of A-minor interactions called G-minors were found in the SAM
      I and FMN riboswitches where they appear to be involved in the recognition of the
      respective ligand's functional groups. From our structural survey as well as
      corresponding structure and sequence alignments, the agreement between motif
      occurrences and conservations are very prominent across the representative
      riboswitches. Our analysis provide evidence that some of these tertiary
      interactions are essential components to form the structure where their sequence
      positions are conserved despite a high degree of diversity in other parts of the
      respective riboswitches sequences. This is indicative of a vital role for these
      tertiary interactions in determining the specific biological function of
      riboswitch. 

PMID- 24040137
TI  - miR-203 inhibits cell proliferation and migration of lung cancer cells by
      targeting PKCalpha.
AB  - PKCalpha (protein kinase C alpha, PRKCA) is an important protein involved in
      several steps of signaling pathways in lung cancer, and microRNAs (miRNAs) have
      also been shown to participate in lung carcinogenesis. However, it is not clear
      how PKCalpha and miRNAs are correlated in the disease. In this report, we aimed
      to identify novel miRNAs that target PKCalpha and to study their biological
      function. Using bioinformatics analysis, we predicted one novel candidate, miR
      203, and found differential expression patterns of miR-203 and PKCalpha in human
      lung cancer tissues. Moreover, we experimentally validated miR-203 as a direct
      regulator of PKCalpha. Finally, we demonstrated that the targeting of PKCalpha by
      miR-203 played a critical role in regulating cell proliferation, apoptosis and
      migration in lung cancer cells. In summary, this study identifies a novel miRNA
      that targets PKCalpha and illustrates that the downregulation of PKCalpha by miR
      203 modulates biological processes in lung cancer cells. 

PMID- 24040138
TI  - Zygotic G2/M cell cycle arrest induced by ATM/Chk1 activation and DNA repair in
      mouse embryos fertilized with hydrogen peroxide-treated epididymal mouse sperm.
AB  - Human sperm cryopreservation for assisted reproduction is compromised by ROS
      induced sperm cryodamage. Our previous model study in which mouse sperm were
      treated with H2O2 to simulate sperm DNA-damage caused by cryopreservation-induced
      ROS have discovered that mouse embryos fertilized with treated sperm showed a
      delay in cleavage that might be associated with cell cycle arrest. The DNA-damage
      checkpoint pathway underlying the delay remained elusive. Moreover, our previous
      study have also indicated that gammaH2AX, the DNA-damage repair marker, was
      functional in mouse embryos similarly fertilized, but the completeness and
      correctness are unknown and warrant more studies because insufficiency of
      completeness and correctness of DNA repair would otherwise trigger apoptosis.
      Based on the aforementioned model, we used embryo culture, inverted microscope,
      BrdU incorporation and immunofluorescence to explore the cell cycle phase that
      arrest occurred and the underlying DNA-damage checkpoint pathway in mouse zygotes
      fertilized with H2O2-treated sperm. We also adopted Tunel to investigate the
      apoptosis of mouse embryos similarly fertilized at different developmental stages
      to testify the completeness and correctness of sperm-derived DNA-damage repair.
      We found G2/M cell cycle arrest in zygotes fertilized with H2O2-treated sperm.
      ATM (pSer-1981) and Chk1 (pSer-345) activations, rather than ATR (pSer-428) and
      Chk2 (pThr-68), were detected in zygotes of the treated group. The apoptosis of
      embryos of different developmental stages of the treated group weren't different
      from those of the untreated group. In conclusions, ATM (pSer-1981)-Chk1 (pSer
      345) cascade might have mediated G2/M cell cycle arrest and allowed time to
      facilitate sperm-derived DNA-damage repair in mouse zygotes fertilized with
      oxygen-stressed sperm, and the DNA-damage repair might be effective.

PMID- 24040139
TI  - The case for using the repeatability coefficient when calculating test-retest
      reliability.
AB  - The use of standardised tools is an essential component of evidence-based
      practice. Reliance on standardised tools places demands on clinicians to
      understand their properties, strengths, and weaknesses, in order to interpret
      results and make clinical decisions. This paper makes a case for clinicians to
      consider measurement error (ME) indices Coefficient of Repeatability (CR) or the
      Smallest Real Difference (SRD) over relative reliability coefficients like the
      Pearson's (r) and the Intraclass Correlation Coefficient (ICC), while selecting
      tools to measure change and inferring change as true. The authors present
      statistical methods that are part of the current approach to evaluate test-retest
      reliability of assessment tools and outcome measurements. Selected examples from
      a previous test-retest study are used to elucidate the added advantages of
      knowledge of the ME of an assessment tool in clinical decision making. The CR is
      computed in the same units as the assessment tool and sets the boundary of the
      minimal detectable true change that can be measured by the tool. 

PMID- 24040140
TI  - Genes required for growth at high hydrostatic pressure in Escherichia coli K-12
      identified by genome-wide screening.
AB  - Despite the fact that much of the global microbial biosphere is believed to exist
      in high pressure environments, the effects of hydrostatic pressure on microbial
      physiology remain poorly understood. We use a genome-wide screening approach,
      combined with a novel high-throughput high-pressure cell culture method, to
      investigate the effects of hydrostatic pressure on microbial physiology in vivo.
      The Keio collection of single-gene deletion mutants in Escherichia coli K-12 was
      screened for growth at a range of pressures from 0.1 MPa to 60 MPa. This led to
      the identification of 6 genes, rodZ, holC, priA, dnaT, dedD and tatC, whose
      products were required for growth at 30 MPa and a further 3 genes, tolB, rffT and
      iscS, whose products were required for growth at 40 MPa. Our results support the
      view that the effects of pressure on cell physiology are pleiotropic, with DNA
      replication, cell division, the cytoskeleton and cell envelope physiology all
      being potential failure points for cell physiology during growth at elevated
      pressure. 

PMID- 24040141
TI  - The polycomb group protein ring1b/rnf2 is specifically required for craniofacial
      development.
AB  - Polycomb group (PcG) genes are chromatin modifiers that mediate epigenetic
      silencing of target genes. PcG-mediated epigenetic silencing is implicated in
      embryonic development, stem cell plasticity, cell fate maintenance, cellular
      differentiation and cancer. However, analysis of the roles of PcG proteins in
      maintaining differentiation programs during vertebrate embryogenesis has been
      hampered due to the early embryonic lethality of several PcG knock-outs in the
      mouse. Here, we show that zebrafish Ring1b/Rnf2, the single E3 ubiquitin ligase
      in the Polycomb Repressive Complex 1, critically regulates the developmental
      program of craniofacial cell lineages. Zebrafish ring1b mutants display a severe
      craniofacial phenotype, which includes an almost complete absence of all cranial
      cartilage, bone and musculature. We show that Cranial Neural Crest (CNC)-derived
      cartilage precursors migrate correctly into the pharyngeal arches, but fail to
      differentiate into chondrocytes. This phenotype is specific for cartilage
      precursors, since other neural crest-derived cell lineages, including glia,
      neurons and chromatophores, are formed normally in ring1b mutants. Our results
      therefore reveal a critical and specific role for Ring1b in promoting the
      differentiation of cranial neural crest cells into chondrocytes. The molecular
      mechanisms underlying the pathogenesis of craniofacial abnormalities, which are
      among the most common genetic birth defects in humans, remain poorly understood.
      The zebrafish ring1b mutant provides a molecular model for investigating these
      mechanisms and may lead to the discovery of new treatments or preventions of
      craniofacial abnormalities. 

PMID- 24040142
TI  - Silver nanoparticle protein corona composition in cell culture media.
AB  - The potential applications of nanomaterials as drug delivery systems and in other
      products continue to expand. Upon introduction into physiological environments
      and driven by energetics, nanomaterials readily associate proteins forming a
      protein corona (PC) on their surface. This PC influences the nanomaterial's
      surface characteristics and may impact their interaction with cells. To determine
      the biological impact of nanomaterial exposure as well as nanotherapeutic
      applications, it is necessary to understand PC formation. Utilizing a label-free
      mass spectrometry-based proteomics approach, we examined the composition of the
      PC for a set of four silver nanoparticles (AgNPs) including citrate-stabilized
      and polyvinlypyrrolidone-stabilized (PVP) colloidal silver (20 or 110 nm
      diameter). To simulate cell culture conditions, AgNPs were incubated for 1 h in
      Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum,
      washed, coronal proteins solubilized, and proteins identified and quantified by
      label-free LC-MS/MS. To determine which attributes influence PC formation, the
      AgNPs were characterized in both water and cell culture media with 10% FBS. All
      AgNPs associated a common subset of 11 proteins including albumin,
      apolipoproteins, keratins, and other serum proteins. 110 nm citrate- and PVP
      stabilized AgNPs were found to bind the greatest number of proteins (79 and 85
      respectively) compared to 20 nm citrate- and PVP-stabilized AgNPs (45 and 48
      respectively), suggesting a difference in PC formation based on surface
      curvature. While no relationships were found for other protein parameters
      (isoelectric point or aliphatic index), the PC on 20 nm AgNPs (PVP and citrate)
      consisted of more hydrophobic proteins compared to 110 nm AgNPs implying that
      this class of proteins are more receptive to curvature-induced folding and
      crowding in exchange for an increased hydration in the aqueous environment. These
      observations demonstrate the significance of electrostatic and hydrophobic
      interactions in the formation of the PC which may have broad biological and
      toxicological implications. 

PMID- 24040143
TI  - Ceriodaphnia dubia as a potential bio-indicator for assessing acute aluminum
      oxide nanoparticle toxicity in fresh water environment.
AB  - Growing nanomaterials based consumer applications have raised concerns about
      their potential release into the aquatic ecosystems and the consequent
      toxicological impacts. So environmental monitoring of the nanomaterials in
      aqueous systems becomes imperative. The current study reveals the potential of
      Ceriodaphnia dubia (C. dubia) as a bio-indicator for aluminum oxide nanoparticles
      in a fresh water aquatic ecosystem where it occupies an important ecological
      niche as a primary consumer. This study aims to investigate the aluminium oxide
      nanoparticle induced acute toxicity on Ceriodaphnia dubia in a freshwater system.
      The bioavailability of the aluminum oxide nanoparticles has been studied with
      respect to their aggregation behavior in the system and correlated with the
      toxicity endpoints. The oxidative stress generated by the particles contributed
      greatly toward their toxicity. The crucial role of leached aluminium ion mediated
      toxicity in the later phases (48 h and 72 h) in conjunction with the effects from
      the nano-sized particles in the initial phases (24 h) puts forth the dynamics of
      nanotoxicity in the test system. The internalization of nanoparticles (both gross
      and systemic uptake) as substantiated through the transmission electron
      microscopy (TEM) and inductively coupled plasma optical emission spectral (ICP
      OES) analysis was another major contributor toward acute toxicity. Concluding the
      present study, Ceriodaphnia dubia can be a promising candidate for bio-monitoring
      the aluminium oxide nanoparticles in a fresh water system. 

PMID- 24040144
TI  - An improved quantitative approach for the assessment of mitochondrial
      fragmentation in chemoresistant ovarian cancer cells.
AB  - Mitochondrial fission is a process that involves cleavage of mitochondria into
      smaller fragments and is regulated by the GTPase Dynamin-related protein 1
      (Drp1). Higher levels of mitochondrial fission are associated with the induction
      of apoptosis in cancer cells. However, current methods to accurately quantify
      mitochondrial fission in order to compare therapeutics that target this process
      are often ambiguous or rely on subjective assessment. Mitochondria are also prone
      to aggregation, making accurate analysis difficult. Here we describe an improved
      approach for the quantification of mitochondrial fragmentation involving several
      differences from currently existing methods. Cells are first subjected to
      cytological centrifugation, which reduces cellular z-axis height and disperses
      individual mitochondria for easier observation. Three commercially available
      fluorescence analysis tools are then applied to disambiguate remaining
      mitochondrial clusters that require further inspection. Finally, cut-off scoring
      is applied, which can be tailored to individual cell type. The resultant approach
      allows for the efficient and objective assessment of mitochondrial fragmentation
      in response to treatment. We applied this technique to an experimental question
      involving chemosensitive and chemoresistant ovarian cancer (OVCA) cells.
      Cisplatin and the phytochemical piperlongumine were found to induce both
      mitochondrial fission and apoptosis in chemosensitive cells, while only
      piperlongumine was able to elicit these cellular responses in chemoresistant
      cells. Piperlongumine-induced apoptosis appeared to be mediated by Drp1-dependent
      mitochondrial fission since the apoptotic response was attenuated by the presence
      of the Drp1 inhibitor mDivi-1. Our study provides groundwork for a more objective
      approach to the quantification of mitochondrial fragmentation, and sheds further
      light on a potential mechanism of action for piperlongumine in the treatment of
      chemoresistant OVCA. 

PMID- 24040145
TI  - Staphylococcus aureus activates the NLRP3 inflammasome in human and rat
      conjunctival goblet cells.
AB  - The conjunctiva is a moist mucosal membrane that is constantly exposed to an
      array of potential pathogens and triggers of inflammation. The NACHT, leucine
      rich repeat (LRR), and pyrin domain-containing protein 3 (NLRP3) is a Nod-like
      receptor that can sense pathogens or other triggers, and is highly expressed in
      wet mucosal membranes. NLRP3 is a member of the multi-protein complex termed the
      NLRP3 inflammasome that activates the caspase 1 pathway, inducing the secretion
      of biologically active IL-1beta, a major initiator and promoter of inflammation.
      The purpose of this study was to: (1) determine whether NLRP3 is expressed in the
      conjunctiva and (2) determine whether goblet cells specifically contribute to
      innate mediated inflammation via secretion of IL-1beta. We report that the
      receptors known to be involved in the priming and activation of the NLRP3
      inflammasome, the purinergic receptors P2X4 and P2X7 and the bacterial Toll-like
      receptor 2 are present and functional in conjunctival goblet cells. Toxin
      containing Staphylococcus aureus (S. aureus), which activates the NLRP3
      inflammasome, increased the expression of the inflammasome proteins NLRP3, ASC
      and pro- and mature caspase 1 in conjunctival goblet cells. The biologically
      active form of IL-1beta was detected in goblet cell culture supernatants in
      response to S. aureus, which was reduced when the cells were treated with the
      caspase 1 inhibitor Z-YVAD. We conclude that the NLRP3 inflammasome components
      are present in conjunctival goblet cells. The NRLP3 inflammasome appears to be
      activated in conjunctival goblet cells by toxin-containing S. aureus via the
      caspase 1 pathway to secrete mature IL1-beta. Thus goblet cells contribute to the
      innate immune response in the conjunctiva by activation of the NLRP3
      inflammasome. 

PMID- 24040146
TI  - Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar
      morphogenesis.
AB  - BRIP1 is a DNA helicase that directly interacts with the C-terminal BRCT repeat
      of the breast cancer susceptibility protein BRCA1 and plays an important role in
      BRCA1-dependent DNA repair and DNA damage-induced checkpoint control. Recent
      studies implicate BRIP1 as a moderate/low-penetrance breast cancer susceptibility
      gene. However, the phenotypic effects of BRIP1 dysfunction and its role in breast
      cancer tumorigenesis remain unclear. To explore the function of BRIP1 in acinar
      morphogenesis of mammary epithelial cells, we generated BRIP1-knockdown MCF-10A
      cells by short hairpin RNA (shRNA)-mediated RNA interference and examined its
      effect in a three-dimensional culture model. Genome-wide gene expression
      profiling by microarray and quantitative RT-PCR were performed to identify
      alterations in gene expression in BRIP1-knockdown cells compared with control
      cells. The microarray data were further investigated using the pathway analysis
      and Gene Set Enrichment Analysis (GSEA) for pathway identification. BRIP1
      knockdown in non-malignant MCF-10A mammary epithelial cells by RNA interference
      induced neoplastic-like changes such as abnormal cell adhesion, increased cell
      proliferation, large and irregular-shaped acini, invasive growth, and defective
      lumen formation. Differentially expressed genes, including MCAM, COL8A1, WIPF1,
      RICH2, PCSK5, GAS1, SATB1, and ELF3, in BRIP1-knockdown cells compared with
      control cells were categorized into several functional groups, such as cell
      adhesion, polarity, growth, signal transduction, and developmental process.
      Signaling-pathway analyses showed dysregulation of multiple cellular signaling
      pathways, involving LPA receptor, Myc, Wnt, PI3K, PTEN as well as DNA damage
      response, in BRIP1-knockdown cells. Loss of BRIP1 thus disrupts normal mammary
      morphogenesis and causes neoplastic-like changes, possibly via dysregulating
      multiple cellular signaling pathways functioning in the normal development of
      mammary glands. 

PMID- 24040147
TI  - Glyoxalase 1-419C>A variant is associated with oxidative stress: implications in
      prostate cancer progression.
AB  - Glyoxalase 1 is a scavenging enzyme of potent precursors in reactive oxygen
      species formation and is involved in the occurrence and progression of human
      malignancies. Glyoxalase I A111E polymorphism has been suggested to influence its
      enzymatic activity. The present study was aimed at investigating the association
      of this polymorphism with oxidative stress and its implications in prostate
      cancer progression or survival. The polymorphism was genotyped in human
      differently aggressive and invasive prostate cancer cell lines, in 571 prostate
      cancer or 588 benign prostatic hyperplasia patients, and 580 healthy subjects by
      Polymerase Chain Reaction/Restriction Fragment Length Polymorphism. Glyoxalase 1
      activity, the pro-oxidant Glyoxalase 1-related Argpyrimidine and oxidative stress
      biomarkers were evaluated by biochemical analyses. Glyoxalase 1 polymorphism was
      associated with an increase in Glyoxalase 1-related pro-oxidant Argpyrimidine and
      oxidative stress levels and cancer progression. The mutant A allele conferred a
      modest risk of prostate cancer, a marked risk of prostate cancer progression and
      a lower survival time, compared to the wild C allele. The results of our
      exploratory study point out a significant role for Glyoxalase 1 in prostate
      cancer progression, providing an additional candidate for risk assessment in
      prostate cancer patients and an independent prognostic factor for survival.
      Finally, we provided evidence of the biological plausibility of Glyoxalase 1
      polymorphism, either alone or in combination with other ones, all related to
      oxidative stress control that represents a key event in PCa development and
      progression. 

PMID- 24040148
TI  - Depletion of the p43 mitochondrial T3 receptor increases Sertoli cell
      proliferation in mice.
AB  - Among T3 receptors, TRalpha1 is ubiquitous and its deletion or a specific
      expression of a dominant-negative TRalpha1 isoform in Sertoli cell leads to an
      increase in testis weight and sperm production. The identification of a 43-kDa
      truncated form of the nuclear receptor TRalpha1 (p43) in the mitochondrial matrix
      led us to test the hypothesis that this mitochondrial transcription factor could
      regulate Sertoli cell proliferation. Here we report that p43 depletion in mice
      increases testis weight and sperm reserve. In addition, we found that p43
      deletion increases Sertoli cell proliferation in postnatal testis at 3 days of
      development. Electron microscopy studies evidence an alteration of mitochondrial
      morphology observed specifically in Sertoli cells of p43-/- mice. Moreover, gene
      expression studies indicate that the lack of p43 in testis induced an alteration
      of the mitochondrial-nuclear cross-talk. In particular, the up-regulation of Cdk4
      and c-myc pathway in p43-/- probably explain the extended proliferation recorded
      in Sertoli cells of these mice. Our finding suggests that T3 limits post-natal
      Sertoli cell proliferation mainly through its mitochondrial T3 receptor p43. 

PMID- 24040149
TI  - Elevated serum iron is a potent biomarker for spirometric resistance to cigarette
      smoke among Japanese males: the Takahata study.
AB  - Chronic obstructive pulmonary disease is a common disability among elderly
      subjects with a heavy cigarette smoking habit. In contrast to the population that
      is susceptible to smoking, in whom pulmonary function worsens with the length of
      exposure to cigarette smoke, there are elderly individuals whose pulmonary
      function is not impaired. However, to date, the characteristics of this resistant
      smoking population have not been investigated. We aimed to identify a biomarker
      in individuals in whom lung health is maintained despite smoking. Blood sampling
      and spirometry were performed on 3,257 subjects who participated in a community
      based annual health check in Takahata, Japan, from 2004 to 2006. We selected 117
      elderly smokers (age >=70, Brinkman index >=600, smoking years >=30). The
      'smoking resistant' group met the following criteria: FEV1/FVC >=0.7, and
      FEV1%predicted >=80. Spirometry was re-evaluated in 147 male, current smokers in
      2009. Baseline serum iron (sFe) levels were higher in the smoke resistant group
      compared with the non-resistant group. In those with low sFe levels, FEV1/FVC was
      reduced in male subjects. These spirometric measures were positively associated
      with sFe levels in men. Multiple linear regression analysis revealed that sFe
      levels were predictive for spirometric values, independent of other clinical
      factors. In addition, sFe levels were predictive for a decline in FEV1.Serum iron
      levels may be a biomarker for the spirometric susceptibility of individuals to
      cigarette smoke. 

PMID- 24040150
TI  - Fatty acid transporter CD36 mediates hypothalamic effect of fatty acids on food
      intake in rats.
AB  - Variations in plasma fatty acid (FA) concentrations are detected by FA sensing
      neurons in specific brain areas such as the hypothalamus. These neurons play a
      physiological role in the control of food intake and the regulation of hepatic
      glucose production. Le Foll et al. previously showed in vitro that at least 50%
      of the FA sensing in ventromedial hypothalamic (VMH) neurons is attributable to
      the interaction of long chain FA with FA translocase/CD36 (CD36). The present
      work assessed whether in vivo effects of hypothalamic FA sensing might be partly
      mediated by CD36 or intracellular events such as acylCoA synthesis or beta
      oxidation. To that end, a catheter was implanted in the carotid artery toward the
      brain in male Wistar rats. After 1 wk recovery, animals were food-deprived for 5
      h, then 10 min infusions of triglyceride emulsion, Intralipid +/- heparin (IL,
      IL(H), respectively) or saline/heparin (SH) were carried out and food intake was
      assessed over the next 5 h. Experimental groups included: 1) Rats previously
      injected in ventromedian nucleus (VMN) with shRNA against CD36 or scrambled RNA;
      2) Etomoxir (CPT1 inhibitor) or saline co-infused with IL(H)/S(H); and 3)
      Triacsin C (acylCoA synthase inhibitor) or saline co-infused with IL(H)/S(H).
      IL(H) significantly lowered food intake during refeeding compared to S(H)
      (p<0.001). Five hours after refeeding, etomoxir did not affect this inhibitory
      effect of IL(H) on food intake while VMN CD36 depletion totally prevented it.
      Triacsin C also prevented IL(H) effects on food intake. In conclusion, the effect
      of FA to inhibit food intake is dependent on VMN CD36 and acylCoA synthesis but
      does not required FA oxidation.

PMID- 24040151
TI  - Clinical predictors and accuracy of empiric tuberculosis treatment among sputum
      smear-negative HIV-infected adult TB suspects in Uganda.
AB  - INTRODUCTION: The existing diagnostic algorithms for sputum smear-negative
      tuberculosis (TB) are complicated, time-consuming, and often difficult to
      implement. The decision to initiate TB treatment in resource-limited countries is
      often largely based on clinical predictors. We sought to determine the clinical
      predictors and accuracy of empiric TB treatment initiation in HIV-infected sputum
      smear-negative TB suspects using sputum culture as a reference standard. SETTING:
      Out-patient HIV-TB integrated urban clinic in Kampala, Uganda. METHODS: HIV
      infected TB suspects were screened using sputum smear microscopy, and
      mycobacterial sputum liquid and solid cultures were performed. Smear results were
      made available to the clinician who made a clinical decision on empiric TB
      treatment initiation for sputum smear-negative patients. Clinic records were
      reviewed for patients whose sputum smears were negative to collect data on socio
      demographics, TB symptomatology, chest X-ray findings, CD4 cell counts and TB
      treatment initiation. RESULTS: Of 253 smear-negative TB suspects, 56% (142/253)
      were females, median age 38 IQR (31-44) years, with a median CD4 cell count of
      291 IQR (150-482) cells/mm(3). Of the 85 (33.6%) smear-negative patients
      empirically initiated on TB treatment, 35.3% (n = 30) were sputum culture
      positive compared to only 18 (10.7%) of the 168 untreated patients (p<0.001).
      Abnormal chest X-ray [aOR 10.18, 95% CI (3.14-33.00), p<0.001] and advanced HIV
      clinical stage [aOR 3.92, 95% CI (1.20-12.85), p = 0.024] were significantly
      associated with empiric TB treatment initiation. The sensitivity and specificity
      of empiric TB treatment initiation in the diagnosis of TB in HIV-infected
      patients after negative smear microscopy was 62.5% and 73.7% respectively.
      CONCLUSION: In resource-limited settings, clinically advanced HIV and abnormal
      chest X-ray significantly predict a clinical decision to empirically initiate TB
      treatment in smear-negative HIV-infected patients. Empiric TB treatment
      initiation correlates poorly with TB cultures. Affordable, accurate and rapid
      point-of-care diagnostics are needed in resource-limited settings to more
      accurately determine which HIV-infected TB suspects have smear-negative TB.

PMID- 24040152
TI  - Small intestinal nematode infection of mice is associated with increased
      enterobacterial loads alongside the intestinal tract.
AB  - Parasitic nematodes are potent modulators of immune reactivity in mice and men.
      Intestinal nematodes live in close contact with commensal gut bacteria, provoke
      biased Th2 immune responses upon infection, and subsequently lead to changes in
      gut physiology. We hypothesized that murine nematode infection is associated with
      distinct changes of the intestinal bacterial microbiota composition. We here
      studied intestinal inflammatory and immune responses in mice following infection
      with the hookworm Heligmosomoides polygyrus bakeri and applied cultural and
      molecular techniques to quantitatively assess intestinal microbiota changes in
      the ileum, cecum and colon. At day 14 post nematode infection, mice harbored
      significantly higher numbers of gamma-Proteobacteria/Enterobacteriaceae and
      members of the Bacteroides/Prevotella group in their cecum as compared to
      uninfected controls. Abundance of Gram-positive species such as Lactobacilli,
      Clostridia as well as the total bacterial load was not affected by worm
      infection. The altered microbiota composition was independent of the IL-4/-13 -
      STAT6 signaling axis, as infected IL-4Ralpha(-/-) mice showed a similar increase
      in enterobacterial loads. In conclusion, infection with an enteric nematode is
      accompanied by distinct intestinal microbiota changes towards higher abundance of
      gram-negative commensal species at the small intestinal site of infection (and
      inflammation), but also in the parasite-free large intestinal tract. Further
      studies should unravel the impact of nematode-induced microbiota changes in
      inflammatory bowel disease to allow for a better understanding of how theses
      parasites interfere with intestinal inflammation and bacterial communities in
      men.

PMID- 24040153
TI  - Sensitivity of a ribavirin resistant mutant of hepatitis C virus to other
      antiviral drugs.
AB  - BACKGROUND: While ribavirin mono-therapy regimens have minimal effect on patients
      with chronic hepatitis C virus (HCV) infections, they can be efficacious when
      combined with interferon. Clinical studies show that interferon-free combination
      therapies containing ribavirin are also efficacious, suggesting that an
      interferon-free therapy could be adopted in the near future. However, generation
      of drug resistant mutants and cross resistance to other drugs could impair the
      efficacy of the treatment. Therefore, understanding the mechanism of HCV
      resistance to ribavirin and cross resistance to other antiviral drugs could be of
      major importance. METHODS: We tested the ability of a J6/JFH1 derived HCV
      ribavirin resistant mutant to grow in tissue cultured Huh7D cells in the presence
      of the mutagen 5-Fluorouracil and the nucleoside analog 2'-C-Methylcytidine.
      Virus replication was assessed by detecting HCV antigens by immunofluorescence
      and by titrating virus present in the supernatants. Recovered viruses were
      amplified by RT-PCR and sequenced. RESULTS: The sensitivity of HCV-RR relative to
      parental J6/JFH1 to the tested drugs varied. HCV-RR was more resistant than
      J6/JFH1 to 5-Fluorouracil but was not more resistant than J6/JFH1 to 2'-C
      Methylcytidine. Growth of HCV-RR in 5-Fluorouracil allowed the selection of an
      HCV-RR derived mutant resistant to 5-Fluorouracil (HCV-5FU). HCV-5FU grows to
      moderate levels in the presence of high concentrations of 5-Fluorouracil and to
      parental levels in the absence of the drug. Sequence of its genome shows that HCV
      5FU accumulated multiple synonymous and non-synonymous mutations. CONCLUSIONS:
      These results indicate that determinants of resistance to ribavirin could also
      confer resistance to other anti-HCV drugs, shedding light toward understanding
      the mechanism of action of ribavirin and highlighting the importance of
      combination drug selection for HCV treatment. The results also show that it is
      possible to select a 5-Fluorouracil HCV resistant mutant that replicates to
      levels similar to parental virus when grown in the absence of 5-Fluorouracil.

PMID- 24040154
TI  - The bZIP protein MeaB mediates virulence attributes in Aspergillus flavus.
AB  - LaeA is a fungal specific virulence factor of both plant and human pathogenic
      fungi. Transcriptional profiles of laeA mutants have been successfully exploited
      to identify regulatory mechanisms of secondary metabolism in fungi; here we use
      laeA mutants as tools to elucidate virulence attributes in Aspergillus flavus.
      Microarray expression profiles of DeltalaeA and over-expression laeA (OE::laeA)
      were compared to wild type A. flavus. Strikingly, several nitrogen metabolism
      genes are oppositely mis-regulated in the DeltalaeA and OE::laeA mutants. One of
      the nitrogen regulatory genes, the bZIP encoding meaB, is up-regulated in
      DeltalaeA. Significantly, over-expression of meaB (OE::meaB) phenocopies the
      decreased virulence attributes of a DeltalaeA phenotype including decreased
      colonization of host seed, reduced lipase activity and loss of aflatoxin B1
      production in seed. However, a double knock-down of laeA and meaB (KD::laeA,meaB)
      demonstrated that KD::laeA,meaB closely resembled DeltalaeA rather than wild type
      or DeltameaB in growth, aflatoxin biosynthesis and sclerotia production thus
      suggesting that meaB does not contribute to the DeltalaeA phenotype. MeaB and
      LaeA appear to be part of regulatory networks that allow them to have both shared
      and distinct roles in fungal biology. 

PMID- 24040155
TI  - Microarray profiling of mononuclear peripheral blood cells identifies novel
      candidate genes related to chemoradiation response in rectal cancer.
AB  - Preoperative chemoradiation significantly improves oncological outcome in locally
      advanced rectal cancer. However there is no effective method of predicting tumor
      response to chemoradiation in these patients. Peripheral blood mononuclear cells
      have emerged recently as pathology markers of cancer and other diseases, making
      possible their use as therapy predictors. Furthermore, the importance of the
      immune response in radiosensivity of solid organs led us to hypothesized that
      microarray gene expression profiling of peripheral blood mononuclear cells could
      identify patients with response to chemoradiation in rectal cancer. Thirty five
      35 patients with locally advanced rectal cancer were recruited initially to
      perform the study. Peripheral blood samples were obtained before neaodjuvant
      treatment. RNA was extracted and purified to obtain cDNA and cRNA for
      hybridization of microarrays included in Human WG CodeLink bioarrays.
      Quantitative real time PCR was used to validate microarray experiment data.
      Results were correlated with pathological response, according to Mandard's
      criteria and final UICC Stage (patients with tumor regression grade 1-2 and
      downstaging being defined as responders and patients with grade 3-5 and no
      downstaging as non-responders). Twenty seven out of 35 patients were finally
      included in the study. We performed a multiple t-test using Significance Analysis
      of Microarrays, to find those genes differing significantly in expression,
      between responders (n = 11) and non-responders (n = 16) to CRT. The differently
      expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and
      ZFP36. The measurement of FALZ (p = 0.029) gene expression level determined by
      qRT-PCR, showed statistically significant differences between the two groups.
      Gene expression profiling reveals novel genes in peripheral blood samples of
      mononuclear cells that could predict responders and non-responders to
      chemoradiation in patients with locally advanced rectal cancer. Moreover, our
      investigation added further evidence to the importance of mononuclear cells'
      mediated response in the neoadjuvant treatment of rectal cancer. 

PMID- 24040156
TI  - Educational intervention improves anticoagulation control in atrial fibrillation
      patients: the TREAT randomised trial.
AB  - BACKGROUND: Stroke prevention in atrial fibrillation (AF), most commonly with
      warfarin, requires maintenance of a narrow therapeutic target (INR 2.0 to 3.0)
      and is often poorly controlled in practice. Poor patient-understanding
      surrounding AF and its treatment may contribute to the patient's willingness to
      adhere to recommendations. METHOD: A theory-driven intervention, developed using
      patient interviews and focus groups, consisting of a one-off group session (1-6
      patients) utilising an "expert-patient" focussed DVD, educational booklet, self
      monitoring diary and worksheet, was compared in a randomised controlled trial
      (ISRCTN93952605) against usual care, with patient postal follow-ups at 1, 2, 6,
      and 12-months. Ninety-seven warfarin-naive AF patients were randomised to
      intervention (n=46, mean age (SD) 72.0 (8.2), 67.4% men), or usual care (n=51,
      mean age (SD) 73.7 (8.1), 62.7% men), stratified by age, sex, and recruitment
      centre. Primary endpoint was time within therapeutic range (TTR); secondary
      endpoints included knowledge, quality of life, anxiety/depression, beliefs about
      medication, and illness perceptions. MAIN FINDINGS: Intervention patients had
      significantly higher TTR than usual care at 6-months (76.2% vs. 71.3%; p=0.035);
      at 12-months these differences were not significant (76.0% vs. 70.0%; p=0.44).
      Knowledge increased significantly across time (F (3, 47) = 6.4; p<0.01), but
      there were no differences between groups (F (1, 47) = 3.3; p = 0.07). At 6
      months, knowledge scores predicted TTR (r=0.245; p=0.04). Patients' scores on
      subscales representing their perception of the general harm and overuse of
      medication, as well as the perceived necessity of their AF specific medications
      predicted TTR at 6- and 12-months. CONCLUSIONS: A theory-driven educational
      intervention significantly improves TTR in AF patients initiating warfarin during
      the first 6-months. Adverse clinical outcomes may potentially be reduced by
      improving patients' understanding of the necessity of warfarin and reducing their
      perception of treatment harm. Improving education provision for AF patients is
      essential to ensure efficacious and safe treatment. The trial is registered with
      Current Controlled Trials, ISRCTN93952605, and details are available at
      www.controlled-trials.com/ISRCTN93952605.

PMID- 24040157
TI  - Radioactive 125I seed inhibits the cell growth, migration, and invasion of
      nasopharyngeal carcinoma by triggering DNA damage and inactivating VEGF-A/ERK
      signaling.
AB  - Although radiotherapy technology has progressed rapidly in the past decade, the
      inefficiency of radiation and cancer cell resistance mean that the 5-year
      survival rate of patients with nasopharyngeal carcinoma (NPC) is low. Radioactive
      (125)I seed implantation has received increasing attention as a clinical
      treatment for cancers. Vascular endothelial growth factor-A (VEGF-A) is one of
      the most important members of the VEGF family and plays an important role in cell
      migration through the extracellular-signal-regulated kinase (ERK) pathway. Here
      we show that radioactive (125)I seeds more effectively inhibit NPC cell growth
      through DNA damage and subsequent induction of apoptosis, compared with X-ray
      irradiation. Moreover, cell migration was effectively inhibited by (125)I seed
      irradiation through VEGF-A/ERK inactivation. VEGF-A pretreatment significantly
      blocked (125)I seed irradiation-induced inhibition of cell migration by
      recovering the levels of phosphorylated ERK (p-ERK) protein. Interestingly, in
      vivo study results confirmed that (125)I seed irradiation was more effective in
      inhibiting tumor growth than X-ray irradiation. Taken together, these results
      suggest that radioactive (125)I seeds exert novel anticancer activity by
      triggering DNA damage and inactivating VEGF-A/ERK signaling. Our finding provides
      evidence for the efficacy of (125)I seeds for treating NPC patients, especially
      those with local recurrence. 

PMID- 24040158
TI  - Clonal astrocytic response to cortical injury.
AB  - Astrocytes are a heterogeneous population of glial cells with multifaceted roles
      in the central nervous system. Recently, the new method for the clonal analysis
      Star Track evidenced the link between astrocyte heterogeneity and lineage. Here,
      we tested the morphological response to mechanical injury of clonally related
      astrocytes using the Star Track approach, which labels each cell lineage with a
      specific code of colors. Histological and immunohistochemical analyses at 7 days
      post injury revealed a variety of morphological changes that were different among
      distinct clones. In many cases, cells of the same clone responded equally to the
      injury, suggesting the dependence on their genetic codification (intrinsic
      response). However, in other cases cells of the same clone responded differently
      to the injury, indicating their response to extrinsic factors. Thus, whereas some
      clones exhibited a strong morphological alteration or a high proliferative
      response to the injury, other clones located at similar distances to the lesion
      were apparently unresponsive. Concurrence of different clonal responses to the
      injury reveals the importance of the development determining the astrocyte
      features in response to brain injuries. These features should be considered to
      develop therapies that affect glial function. 

PMID- 24040159
TI  - Potentially functional polymorphisms in the CASP7 gene contribute to gastric
      adenocarcinoma susceptibility in an eastern Chinese population.
AB  - BACKGROUND: Caspase 7 (CASP7) is an important regulator and executioner in the
      apoptosis pathway and plays a crucial role in cancer development and progression.
      However, few studies have evaluated associations between functional single
      nucleotide polymorphisms (SNPs) in the 3' untranslational region (UTR) of CASP7
      and risk of gastric cancer. METHODS: In a case-control study of 1117 patients
      with gastric cancer and 1146 cancer-free controls with frequency matching on age
      and sex, we genotyped four potentially functional SNPs (rs4353229T>C,
      rs10787498T>G, rs1127687G>A and rs12247479G>A) located in the microRNA binding
      sites of the CASP7 3' UTR by using Taqman assays and evaluated their associations
      with risk of gastric cancer by using logistic regression analyses as well as
      multifactorial dimension reduction (MDR) analysis. RESULTS: In the single-locus
      analysis, only the CASP7 rs4353229 TT genotype was associated with 0.83-fold
      decreased risk (95% confidence interval [CI] = 0.70-0.98) of gastric cancer under
      a recessive model, compared with the CT/CC genotypes. In the combined analysis of
      all four SNPs, we found that the risk of gastric cancer decreased by 19% in those
      carrying any of the risk genotypes (adjusted odds ratio = 0.81, 95% CI = 0.68
      0.96), compared with those carrying zero risk genotypes, and this risk was more
      evident in subgroups of younger age (<59 years), females, non-smokers, non
      drinkers and patients with non-gastric cardia adenocarcinoma. Further MDR
      analysis suggested some evidence of interactions between the combined genotypes
      and other risk factors for gastric cancer. CONCLUSIONS: Potentially functional
      CASP7 variants may contribute to risk of gastric cancer. Larger studies with
      different ethnic populations are warranted to validate our findings.

PMID- 24040160
TI  - Expression of the chemokine receptor CXCR7 in CXCR4-expressing human 143B
      osteosarcoma cells enhances lung metastasis of intratibial xenografts in SCID
      mice.
AB  - More effective treatment of metastasizing osteosarcoma with a current mean 5-year
      survival rate of less than 20% requires more detailed knowledge on mechanisms and
      key regulatory molecules of the complex metastatic process. CXCR4, the receptor
      of the chemokine CXCL12, has been reported to promote tumor progression and
      metastasis in osteosarcoma. CXCR7 is a recently deorphanized CXCL12-scavenging
      receptor with so far not well-defined functions in tumor biology. The present
      study focused on a potential malignancy enhancing function of CXCR7 in
      interaction with CXCR4 in osteosarcoma, which was investigated in an intratibial
      osteosarcoma model in SCID mice, making use of the human 143B osteosarcoma cell
      line that spontaneously metastasizes to the lung and expresses endogenous CXCR4.
      143B osteosarcoma cells stably expressing LacZ (143B-LacZ cells) were
      retrovirally transduced with a gene encoding HA-tagged CXCR7 (143B-LacZ-X7-HA
      cells). 143B-LacZ-X7-HA cells co-expressing CXCR7 and CXCR4 exhibited CXCL12
      scavenging and enhanced adhesion to IL-1beta-activated HUVEC cells compared to
      143B-LacZ cells expressing CXCR4 alone. SCID mice intratibially injected with
      143B-LacZ-X7-HA cells had significantly (p<0.05) smaller primary tumors, but
      significantly (p<0.05) higher numbers of lung metastases than mice injected with
      143B-LacZ cells. Unexpectedly, 143B-LacZ-X7-HA cells, unlike 143B-LacZ cells,
      also metastasized with high incidence to the auriculum cordis. In conclusion,
      expression of the CXCL12 scavenging receptor CXCR7 in the CXCR4-expressing human
      143B osteosarcoma cell line enhances its metastatic activity in intratibial
      primary tumors in SCID mice that predominantly metastasize to the lung and
      thereby closely mimic the human disease. These findings point to CXCR7 as a
      target, complementary to previously proposed CXCR4, for more effective metastasis
      suppressive treatment in osteosarcoma. 

PMID- 24040161
TI  - Maternal olfactory cues synchronize the circadian system of artificially raised
      newborn rabbits.
AB  - In European newborn rabbits, once-daily nursing acts as a strong non-photic
      entraining cue for the pre-visual circadian system. Nevertheless, there is a lack
      of information regarding which of the non-photic cues are capable of modulating
      pup circadian system. In this study, for the first time, we determined that the
      mammary pheromone 2-methylbut-2-enal (2MB2) presented in the maternal milk acts
      as a non-photic entraining cue. We evaluated the effect of once-daily exposure to
      maternal olfactory cues on the temporal pattern of core body temperature, gross
      locomotor activity and metabolic variables (liver weight, serum glucose,
      triacylglycerides, free fatty acids, cholecystokinin and cholesterol levels) in
      newborn rabbits. Rabbit pups were separated from their mothers from postnatal day
      1 (P1) to P8 and were randomly assigned to one of the following conditions:
      nursed by a lactating doe (NAT); exposed to a 3-min pulse of maternal milk (M
      Milk), mammary pheromone (2MB2), or water (H2O). To eliminate maternal
      stimulation, the pups of the last three groups were artificially fed once every
      24-h. On P8, the rabbits were sacrificed at different times of the day. In
      temperature and activity, the NAT, M-Milk and 2MB2 groups exhibited clear diurnal
      rhythmicity with a conspicuous anticipatory rise hours prior to nursing. In
      contrast, the H2O group exhibited atypical rhythmicity in both parameters,
      lacking the anticipatory component. At the metabolic level, all of the groups
      exhibited a diurnal pattern with similar phases in liver weight and metabolites
      examined. The results obtained in this study suggest that during pre-visual
      stages of development, the circadian system of newborn rabbits is sensitive to
      the maternal olfactory cues contained in milk, indicating that these cues
      function as non-photic entraining signals mainly for the central oscillators
      regulating the expression of temperature and behavior, whereas in metabolic
      diurnal rhythmicity, these cues lack an effect, indicating that peripheral
      oscillators respond to milk administration.

PMID- 24040162
TI  - Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related
      ischemic intolerance.
AB  - Reactive aldehydes can initiate protein oxidative damage which may contribute to
      heart senescence. Sirtuin 1 (SIRT1) is considered to be a potential
      interventional target for I/R injury management in the elderly. We hypothesized
      that aldehyde mediated carbonyl stress increases susceptibility of aged hearts to
      ischemia/reperfusion (I/R) injury, and elucidate the underlying mechanisms with a
      focus on SIRT1. Male C57BL/6 young (4-6 mo) and aged (22-24 mo) mice were
      subjected to myocardial I/R. Cardiac aldehyde dehydrogenase (ALDH2), SIRT1
      activity and protein carbonyls were assessed. Our data revealed that aged heart
      exhibited increased endogenous aldehyde/carbonyl stress due to impaired ALDH2
      activity concomitant with blunted SIRT1 activity (P<0.05). Exogenous toxic
      aldehydes (4-HNE) exposure in isolated cardiomyocyte verified that aldehyde
      induced carbonyl modification on SIRT1 impaired SIRT1 activity leading to worse
      hypoxia/reoxygenation (H/R) injury, which could all be rescued by Alda-1 (ALDH2
      activator) (all P<0.05). However, SIRT1 inhibitor blocked the protective effect
      of Alda-1 on H/R cardiomyocyte. Interestingly, myocardial I/R leads to higher
      carbonylation but lower activity of SIRT1 in aged hearts than that seen in young
      hearts (P<0.05). The application of Alda-1 significantly reduced the
      carbonylation on SIRT1 and markedly improved the tolerance to in vivo I/R injury
      in aged hearts, but failed to protect Sirt1(+/-) knockout mice against myocardial
      I/R injury. This was verified by Alda-1 treatment improved postischemic
      contractile function recovery in ex vivo perfused aged but not in Sirt1(+/-)
      hearts. Thus, aldehyde/carbonyl stress is accelerated in aging heart. These
      results provide a new insight that impaired cardiac SIRT1 activity by carbonyl
      stress plays a critical role in the increased susceptibility of aged heart to I/R
      injury. ALDH2 activation can restore this aging-related myocardial ischemic
      intolerance. 

PMID- 24040163
TI  - Hypoxia-inducible factor-1alpha and MAPK co-regulate activation of hepatic
      stellate cells upon hypoxia stimulation.
AB  - BACKGROUND: Hepatic stellate cell (HSC) plays a key role in pathogenesis of liver
      fibrosis. During liver injury, hypoxia in local micro-environment is inevitable.
      Hif-1alpha is the key transcriptional regulation factor that induces cell's
      adaptive responses to hypoxia. Recently, it was reported that MAPK is involved in
      regulation of Hif-1alpha activity. AIMS: To explore whether Hif-1alpha regulates
      HSC activation upon hypoxia, and whether MAPK affects Hif-1alpha-regulated
      signaling cascades, thus providing new targets for preventing liver fibrosis.
      METHODS: Hif-1alpha expression in livers of Schistosomajaponicum infected BALB/c
      mice was detected with western blot and immunohistochemistry. A rat cell line of
      HSC, HSC-T6, was cultured in 1% oxygen. HSC activation, including F-actin
      reorganization, increase of vimentin and alpha-SMA, was detected with western
      blot or immunocytochemistry. Cells were transfected with specific siRNA to Hif
      1alpha, expression of activation markers, transcription of fibrosis-promoting
      cytokines, secretion of collagen I were detected with western blot, Real Time PCR
      and ELISA. Lysate from HSC-T6 cells pretreated with PD98059, a specific MEK1
      pharmacological inhibitor, was subjected to detect Hif-1alpha ubiquitination and
      nuclear translocation with western blot and immunoprecipitation. RESULTS AND
      CONCLUSIONS: Hif-1alpha apparently increased in liver tissues of
      Schistosomajaponicum infected mice. 1% O2 induced F-actin reorganization,
      increase of Hif-1alpha, vimentin and alpha-SMA in HSC-T6 cells. Hif-1alpha
      Knockdown inhibited HSC-T6 activation, transcription of IL-6, TGF-beta and CTGF
      and secretion of collagen I from HSC-T6 cells upon hypoxia. Inhibition of MAPK
      phosphorylation enhanced Hif-1alpha ubiquitination, and inhibited Hif-1alpha
      translocation into nucleus. Conclusively, Hif-1alpha and MAPK participate in HSC
      activation upon hypoxia.

PMID- 24040164
TI  - Genome-wide discovery and information resource development of DNA polymorphisms
      in cassava.
AB  - Cassava (Manihot esculenta Crantz) is an important crop that provides food
      security and income generation in many tropical countries, and is known for its
      adaptability to various environmental conditions. Its draft genome sequence and
      many expressed sequence tags are now publicly available, allowing the development
      of cassava polymorphism information. Here, we describe the genome-wide discovery
      of cassava DNA polymorphisms. Using the alignment of predicted transcribed
      sequences from the cassava draft genome sequence and ESTs from GenBank, we
      discovered 10,546 single-nucleotide polymorphisms and 647 insertions and
      deletions. To facilitate molecular marker development for cassava, we designed
      9,316 PCR primer pairs to amplify the genomic region around each DNA
      polymorphism. Of the discovered SNPs, 62.7% occurred in protein-coding regions.
      Disease-resistance genes were found to have a significantly higher ratio of
      nonsynonymous-to-synonymous substitutions. We identified 24 read-through (changes
      of a stop codon to a coding codon) and 38 premature stop (changes of a coding
      codon to a stop codon) single-nucleotide polymorphisms, and found that the 5 gene
      ontology terms in biological process were significantly different in genes with
      read-through single-nucleotide polymorphisms compared with all cassava genes. All
      data on the discovered DNA polymorphisms were organized into the Cassava Online
      Archive database, which is available at http://cassava.psc.riken.jp/. 

PMID- 24040165
TI  - Randomly detected genetically modified (GM) maize (Zea mays L.) near a transport
      route revealed a fragile 45S rDNA phenotype.
AB  - Monitoring of genetically modified (GM) crops has been emphasized to prevent
      their potential effects on the environment and human health. Monitoring of the
      inadvertent dispersal of transgenic maize in several fields and transport routes
      in Korea was carried out by qualitative multiplex PCR, and molecular analyses
      were conducted to identify the events of the collected GM maize. Cytogenetic
      investigations through fluorescence in situ hybridization (FISH) of the GM maize
      were performed to check for possible changes in the 45S rDNA cluster because this
      cluster was reported to be sensitive to replication and transcription stress.
      Three GM maize kernels were collected from a transport route near Incheon port,
      Korea, and each was found to contain NK603, stacked MON863 x NK603, and stacked
      NK603 x MON810 inserts, respectively. Cytogenetic analysis of the GM maize
      containing the stacked NK603 x MON810 insert revealed two normal compact 5S rDNA
      signals, but the 45S rDNA showed a fragile phenotype, demonstrating a "beads-on-a
      string" fragmentation pattern, which seems to be a consequence of genetic
      modification. Implications of the 45S rDNA cluster fragility in GM maize are also
      discussed. 

PMID- 24040167
TI  - Assessment of cellular estrogenic activity based on estrogen receptor-mediated
      reduction of soluble-form catechol-O-methyltransferase (COMT) expression in an
      ELISA-based system.
AB  - Xenoestrogens are either natural or synthetic compounds that mimic the effects of
      endogenous estrogen. These compounds, such as bisphenol-A (BPA), and phthalates,
      are commonly found in plastic wares. Exposure to these compounds poses major risk
      to human health because of the potential to cause endocrine disruption. There is
      huge demand for a wide range of chemicals to be assessed for such potential for
      the sake of public health. Classical in vivo assays for endocrine disruption are
      comprehensive but time-consuming and require sacrifice of experimental animals.
      Simple preliminary in vitro screening assays can reduce the time and expense
      involved. We previously demonstrated that catechol-O-methyltransferase (COMT) is
      transcriptionally regulated by estrogen via estrogen receptor (ER). Therefore,
      detecting corresponding changes of COMT expression in estrogen-responsive cells
      may be a useful method to estimate estrogenic effects of various compounds. We
      developed a novel cell-based ELISA to evaluate cellular response to estrogenicity
      by reduction of soluble-COMT expression in ER-positive MCF-7 cells exposed to
      estrogenic compounds. In contrast to various existing methods that only detect
      bioactivity, this method elucidates direct physiological effect in a living cell
      in response to a compound. We validated our assay using three well-characterized
      estrogenic plasticizers - BPA, benzyl butyl phthalate (BBP), and di-n-butyl
      phthalate (DBP). Cells were exposed to either these plasticizers or 17beta
      estradiol (E2) in estrogen-depleted medium with or without an ER-antagonist, ICI
      182,780, and COMT expression assayed. Exposure to each of these plasticizers (10(
      9)-10(-7)M) dose-dependently reduced COMT expression (p<0.05), which was blocked
      by ICI 182,780. Reduction of COMT expression was readily detectable in cells
      exposed to picomolar level of E2, comparable to other in vitro assays of similar
      sensitivity. To satisfy the demand for in vitro assays targeting different
      cellular components, a cell-based COMT assay provides useful initial screening to
      supplement the current assessments of xenoestrogens for potential estrogenic
      activity. 

PMID- 24040166
TI  - Early indications of future cognitive decline: stable versus declining controls.
AB  - This study aimed to identify baseline features of normal subjects that are
      associated with subsequent cognitive decline. Publicly available data from the
      Alzheimer's Disease Neuroimaging Initiative was used to find differences in
      baseline clinical assessments (ADAScog, AVLT, FAQ) between cognitively healthy
      individuals who will suffer cognitive decline within 48 months and those who will
      remain stable for that period. Linear regression models indicated an individual's
      conversion status was significantly associated with certain baseline neuroimaging
      measures, including posterior cingulate glucose metabolism. Linear Discriminant
      Analysis models built with baseline features derived from MRI and FDG-PET
      measures were capable of successfully predicting whether an individual will
      convert to MCI within 48 months or remain cognitively stable. The findings from
      this study support the idea that there exist informative differences between
      normal people who will later develop cognitive impairments and those who will
      remain cognitively stable for up to four years. Further, the feasibility of
      developing predictive models that can detect early states of cognitive decline in
      seemingly normal individuals was demonstrated. 

PMID- 24040168
TI  - Single nucleotide polymorphism network: a combinatorial paradigm for risk
      prediction.
AB  - Risk prediction for a particular disease in a population through SNP genotyping
      exploits tests whose primary goal is to rank the SNPs on the basis of their
      disease association. This manuscript reveals a different approach of predicting
      the risk through network representation by using combined genotypic data (instead
      of a single allele/haplotype). The aim of this study is to classify diseased
      group and prediction of disease risk by identifying the responsible genotype.
      Genotypic combination is chosen from five independent loci present on platelet
      receptor genes P2RY1 and P2RY12. Genotype-sets constructed from combinations of
      genotypes served as a network input, the network architecture constituting super
      nodes (e.g., case and control) and nodes representing individuals, each
      individual is described by a set of genotypes containing M markers (M = number of
      SNP). The analysis becomes further enriched when we consider a set of networks
      derived from the parent network. By maintaining the super-nodes identical, each
      network is carrying an independent combination of M-1 markers taken from M
      markers. For each of the network, the ratio of case specific and control specific
      connections vary and the ratio of super-node specific connection shows
      variability. This method of network has also been applied in another case-control
      study which includes oral cancer, precancer and control individuals to check
      whether it improves presentation and interpretation of data. The analyses reveal
      a perfect segregation between super-nodes, only a fraction of mixed state being
      connected to both the super-nodes (i.e. common genotype set). This kind of
      approach is favorable for a population to classify whether an individual with a
      particular genotypic combination can be in a risk group to develop disease. In
      addition with that we can identify the most important polymorphism whose presence
      or absence in a population can make a large difference in the number of case and
      control individuals. 

PMID- 24040169
TI  - Are hotspots always hotspots? The relationship between diversity, resource and
      ecosystem functions in the Arctic.
AB  - The diversity-ecosystem function relationship is an important topic in ecology
      but has not received much attention in Arctic environments, and has rarely been
      tested for its stability in time. We studied the temporal variability of benthic
      ecosystem functioning at hotspots (sites with high benthic boundary fluxes) and
      coldspots (sites with lower fluxes) across two years in the Canadian Arctic.
      Benthic remineralisation function was measured as fluxes of oxygen, silicic acid,
      phosphate, nitrate and nitrite at the sediment-water interface. In addition we
      determined sediment pigment concentration and taxonomic and functional
      macrobenthic diversity. To separate temporal from spatial variability, we sampled
      the same nine sites from the Mackenzie Shelf to Baffin Bay during the same season
      (summer or fall) in 2008 and 2009. We observed that temporal variability of
      benthic remineralisation function at hotspots is higher than at coldspots and
      that taxonomic and functional macrobenthic diversity did not change significantly
      between years. Temporal variability of food availability (i.e., sediment surface
      pigment concentration) seemed higher at coldspot than at hotspot areas. Sediment
      chlorophyll a (Chl a) concentration, taxonomic richness, total abundance, water
      depth and abundance of the largest gallery-burrowing polychaete
      Lumbrineristetraura together explained 42% of the total variation in fluxes. Food
      supply proxies (i.e., sediment Chl a and depth) split hot- from coldspot stations
      and explained variation on the axis of temporal variability, and macrofaunal
      community parameters explained variation mostly along the axis separating eastern
      from western sites with hot- or coldspot regimes. We conclude that variability in
      benthic remineralisation function, food supply and diversity will react to
      climate change on different time scales, and that their interactive effects may
      hide the detection of progressive change, particularly at hotspots. Time-series
      of benthic functions and its related parameters should be conducted at both hot-
      and coldspots to produce reliable predictive models. 

PMID- 24040171
TI  - Outcome of using small-for-size grafts in living donor liver transplantation
      recipients with high model for end-stage liver disease scores: a single center
      experience.
AB  - AIMS: To evaluate the impact of small-for-size grafts (SFSG) in adult-to-adult
      living donor liver transplantation (AALDLT) on outcomes of recipients with
      different model for end-stage liver disease (MELD) score in a single liver
      transplant center. MATERIALS AND METHODS: Clinical data of 118 patients underwent
      right-lobe AALDLT from January 2004 to December 2011 were retrospectively
      analyzed, Patients were divided into Group L (MELD score <= 25) and Group H (MELD
      score > 25) according to MELD score. The patients were further stratified into
      Group LS (MELD score <= 25, GBWR < 0.8%), Group LN (MELD score <= 25, GBWR >=
      0.8%), Group HS (MELD score > 25, GBWR < 0.8%), and Group HN (MELD score > 25,
      GBWR >= 0.8%) to investigate the impact of graft size on recipients'
      complications and outcomes. Pre-operative characteristics, post-operative
      complications graded by the Clavien score and patient survival were analyzed.
      RESULTS: MELD scores between the two groups were significant different (12.4 +/-
      4.9 vs 34.5 +/- 7.5, P = 0.026). There was no significant difference in
      preoperative demographic data as well as postoperative liver function.
      Complication rate, length of ICU and hospital stay, graft loss, and mortality
      were similar in both groups. The 1- and 3- year survival were similar between
      group H and group L. When recipients were further stratified into group LS, LN,
      HS, and HN, no significant difference was found among groups in 1- and 3- year
      survival rate. In multivariate analysis, HCC was not a predictor for long term
      survival. CONCLUSION: Our single institution experience demonstrates that it is
      safe to use SFSGs in high pre-MELD score recipients with the improvement of
      intensive care and the selection of listing criteria.

PMID- 24040170
TI  - Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site
      study of subjects with different TB and HIV infection states in sub-Saharan
      Africa.
AB  - BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new
      cases and 1.4 million deaths per year. In order to develop a protective vaccine,
      we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb),
      which are relevant to protective immunity in high-endemic areas. METHODS: We
      analysed responses to 23 Mtb antigens in a total of 1247 subjects with different
      HIV and TB status across 5 geographically diverse sites in Africa (South Africa,
      The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay
      followed by IFN-gamma ELISA on the supernatants. Antigens included PPD, ESAT-6
      and Ag85B (dominant antigens) together with novel resuscitation-promoting factors
      (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens,
      starvation-induced antigens and secreted antigens. RESULTS: There was variation
      between sites in responses to the antigens, presumably due to underlying genetic
      and environmental differences. When results from all sites were combined, HIV-
      subjects with active TB showed significantly lower responses compared to both
      TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737)
      and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD,
      Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI)
      compared to TB and TST(-) contacts fewer differences were seen in subjects with
      HIV co-infection, with responses to the mitogen PHA significantly lower in
      subjects with active TB compared to those with LTBI and no difference with any
      antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens
      revealed promising antigens for future vaccine development. The IFN-gamma ELISA
      is a cheap and useful tool for screening potential antigenicity in subjects with
      different ethnic backgrounds and across a spectrum of TB and HIV infection
      states. Analysis of cytokines other than IFN-gamma is currently on-going to
      determine correlates of protection, which may be useful for vaccine efficacy
      trials.

PMID- 24040172
TI  - Image ambiguity and fluency.
AB  - Ambiguity is often associated with negative affective responses, and enjoying
      ambiguity seems restricted to only a few situations, such as experiencing art.
      Nevertheless, theories of judgment formation, especially the "processing fluency
      account", suggest that easy-to-process (non-ambiguous) stimuli are processed
      faster and are therefore preferred to (ambiguous) stimuli, which are hard to
      process. In a series of six experiments, we investigated these contrasting
      approaches by manipulating fluency (presentation duration: 10 ms, 50 ms, 100 ms,
      500 ms, 1000 ms) and testing effects of ambiguity (ambiguous versus non-ambiguous
      pictures of paintings) on classification performance (Part A; speed and accuracy)
      and aesthetic appreciation (Part B; liking and interest). As indicated by signal
      detection analyses, classification accuracy increased with presentation duration
      (Exp. 1a), but we found no effects of ambiguity on classification speed (Exp.
      1b). Fifty percent of the participants were able to successfully classify
      ambiguous content at a presentation duration of 100 ms, and at 500 ms even 75%
      performed above chance level. Ambiguous artworks were found more interesting (in
      conditions 50 ms to 1000 ms) and were preferred over non-ambiguous stimuli at 500
      ms and 1000 ms (Exp. 2a - 2c, 3). Importantly, ambiguous images were nonetheless
      rated significantly harder to process as non-ambiguous images. These results
      suggest that ambiguity is an essential ingredient in art appreciation even though
      or maybe because it is harder to process.

PMID- 24040173
TI  - Genome-wide study of the adaptation of Saccharomyces cerevisiae to the early
      stages of wine fermentation.
AB  - This work was designed to identify yeast cellular functions specifically affected
      by the stress factors predominating during the early stages of wine fermentation,
      and genes required for optimal growth under these conditions. The main
      experimental method was quantitative fitness analysis by means of competition
      experiments in continuous culture of whole genome barcoded yeast knockout
      collections. This methodology allowed the identification of haploinsufficient
      genes, and homozygous deletions resulting in growth impairment in synthetic must.
      However, genes identified as haploproficient, or homozygous deletions resulting
      in fitness advantage, were of little predictive power concerning optimal growth
      in this medium. The relevance of these functions for enological performance of
      yeast was assessed in batch cultures with single strains. Previous studies
      addressing yeast adaptation to winemaking conditions by quantitative fitness
      analysis were not specifically focused on the proliferative stages. In some
      instances our results highlight the importance of genes not previously linked to
      winemaking. In other cases they are complementary to those reported in previous
      studies concerning, for example, the relevance of some genes involved in
      vacuolar, peroxisomal, or ribosomal functions. Our results indicate that
      adaptation to the quickly changing growth conditions during grape must
      fermentation require the function of different gene sets in different moments of
      the process. Transport processes and glucose signaling seem to be negatively
      affected by the stress factors encountered by yeast in synthetic must. Vacuolar
      activity is important for continued growth during the transition to stationary
      phase. Finally, reduced biogenesis of peroxisomes also seems to be advantageous.
      However, in contrast to what was described for later stages, reduced protein
      synthesis is not advantageous for the early (proliferative) stages of the
      fermentation process. Finally, we found adenine and lysine to be in short supply
      for yeast growth in some natural grape musts. 

PMID- 24040174
TI  - Interaction between gamma-aminobutyric acid A receptor genes: new evidence in
      migraine susceptibility.
AB  - Migraine is a common neurological episodic disorder with a female-to-male
      prevalence 3- to 4-fold higher, suggesting a possible X-linked genetic component.
      Our aims were to assess the role of common variants of gamma-aminobutyric acid A
      receptor (GABAAR) genes, located in the X-chromosome, in migraine susceptibility
      and the possible interaction between them. An association study with 188
      unrelated cases and 286 migraine-free controls age- and ethnic matched was
      performed. Twenty-three tagging SNPs were selected in three genes (GABRE, GABRA3
      and GABRQ). Allelic, genotypic and haplotypic frequencies were compared between
      cases and controls. We also focused on gene-gene interactions. The AT genotype of
      rs3810651 of GABRQ gene was associated with an increased risk for migraine (OR:
      4.07; 95% CI: 1.71-9.73, p=0.002), while the CT genotype of rs3902802 (OR: 0.41;
      95% CI: 0.21-0.78, p=0.006) and GA genotype of rs2131190 of GABRA3 gene (OR:
      0.53; 95% CI: 0.32-0.88, p=0.013) seem to be protective factors. All associations
      were found in the female group and maintained significance after Bonferroni
      correction. We also found three nominal associations in the allelic analyses
      although there were no significant results in the haplotypic analyses.
      Strikingly, we found strong interactions between six SNPs encoding for different
      subunits of GABAAR, all significant after permutation correction. To our
      knowledge, we show for the first time, the putative involvement of polymorphisms
      in GABAAR genes in migraine susceptibility and more importantly we unraveled a
      role for novel gene-gene interactions opening new perspectives for the
      development of more effective treatments. 

PMID- 24040175
TI  - Genetic structure of pelagic and littoral cichlid fishes from Lake Victoria.
AB  - The approximately 700 species of cichlids found in Lake Victoria in East Africa
      are thought to have evolved over a short period of time, and they represent one
      of the largest known examples of adaptive radiation. To understand the processes
      that are driving this spectacular radiation, we must determine the present
      genetic structure of these species and elucidate how this structure relates to
      the ecological conditions that caused their adaptation. We analyzed the genetic
      structure of two pelagic and seven littoral species sampled from the southeast
      area of Lake Victoria using sequences from the mtDNA control region and 12
      microsatellite loci as markers. Using a Bayesian model-based clustering method to
      analyze the microsatellite data, we separated these nine species into four
      groups: one group composed of pelagic species and another three groups composed
      mainly of rocky-shore species. Furthermore, we found significant levels of
      genetic variation between species within each group at both marker loci using
      analysis of molecular variance (AMOVA), although the nine species often shared
      mtDNA haplotypes. We also found significant levels of genetic variation between
      populations within species. These results suggest that initial groupings, some of
      which appear to have been related to habitat differences, as well as divergence
      between species within groups took place among the cichlid species of Lake
      Victoria. 

PMID- 24040176
TI  - Serine protease HTRA1 antagonizes transforming growth factor-beta signaling by
      cleaving its receptors and loss of HTRA1 in vivo enhances bone formation.
AB  - HTRA1 is a member of the High Temperature Requirement (HTRA1) family of serine
      proteases, which play a role in several biological and pathological processes. In
      part, HTRA1 regulation occurs by inhibiting the TGF-beta signaling pathway,
      however the mechanism of inhibition has not been fully defined. Previous studies
      have shown that HTRA1 is expressed in a variety of tissues, including sites of
      skeletal development. HTRA1 has also been implicated in the process of bone
      formation, although the precise manner of regulation is still unknown. This study
      investigated how HTRA1 regulates TGF-beta signaling and examined the in vivo
      effects of the loss of HTRA1. We demonstrated that recombinant HTRA1 was capable
      of cleaving both type II and type III TGF-beta receptors (TbetaRII and TbetaRIII)
      in vitro in a dose-dependent manner, but it did not affect the integrity of
      TbetaRI or TGF-beta. Overexpression of HTRA1 led to decreased levels of both
      TbetaRII and III on the cell surface but had no effect on TbetaRI. Silencing
      HTRA1 expression significantly increased TGF-beta binding to the cell surface and
      TGF-beta responsiveness within the cell. To examine the role of HTRA1 in vivo, we
      generated mice with a targeted gene deletion of HTRA1. Embryonic fibroblasts
      isolated from these mice displayed an increase in TGF-beta-induced expression of
      several genes known to promote bone formation. Importantly, the loss of HTRA1 in
      the knockout mice resulted in a marked increase in trabecular bone mass. This
      study has identified a novel regulatory mechanism by which HTRA1 antagonizes TGF
      beta signaling, and has shown that HTRA1 plays a key role in the regulation of
      bone formation. 

PMID- 24040177
TI  - Stochastic simulation of endemic Salmonella enterica serovar Typhi: the
      importance of long lasting immunity and the carrier state.
AB  - BACKGROUND: Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi)
      remains a serious burden of disease, especially in developing countries of Asia
      and Africa. It is estimated that it causes 200,000 deaths per year, mainly in
      children. S. Typhi is an obligate pathogen of humans and although it has a
      relatively complex life cycle with a long lived carrier state, the absence of non
      human hosts suggests that well targeted control methods should have a major
      impact on disease. Newer control methods including new generations of vaccines
      offer hope but their implementation would benefit from quantitative models to
      guide the most cost effective strategies. This paper presents a quantitative
      model of Typhoid disease, immunity and transmission as a first step in that
      process. METHODOLOGY/PRINCIPAL FINDINGS: A stochastic agent-based model has been
      developed that incorporates known features of the biology of typhoid including
      probability of infection, the consequences of infection, treatment options,
      acquisition and loss of immunity as a result of infection and vaccination, the
      development of the carrier state and the impact of environmental or behavioral
      factors on transmission. The model has been parameterized with values derived
      where possible from the literature and where this was not possible, feasible
      parameters space has been determined by sensitivity analyses, fitting the
      simulations to age distribution of field data. The model is able to adequately
      predict the age distribution of typhoid in two settings.
      CONCLUSIONS/SIGNIFICANCE: The modeling highlights the importance of variations in
      the exposure/resistance of infants and young children to infection in different
      settings, especially as this impacts on design of control programs; it predicts
      that naturally induced clinical and sterile immunity to typhoid is long lived and
      highlights the importance of the carrier state especially in areas of low
      transmission.

PMID- 24040178
TI  - Evaluation of the effectiveness of pregabalin in alleviating pain associated with
      fibromyalgia: using functional magnetic resonance imaging study.
AB  - PURPOSE: To assess the efficacy of pregabalin by showing differences in the
      neuronal activities of fibromyalgia (FM) patients before and after longitudinal
      treatment using functional magnetic resonance imaging (fMRI). MATERIALS AND
      METHODS: In total, 21 female patients with FM and 11 age- and gender-matched
      healthy controls participated. FM patients underwent fMRI at baseline and
      following pharmacological therapy with pregabalin to diminish their pain.
      Pressure-pain stimuli were delivered on the subject's thumbnail bed during fMRI
      scans. Brain activation regions in fMRI were evaluated for longitudinal changes
      using a paired t-test. Changes in clinical features were also assessed with the
      Fibromyalgia Impact Questionnaire (FIQ), Brief Fatigue Inventory (BFI), Beck
      Depression Inventory (BDI), Widespread Pain Index (WPI), Symptom Severity Scale
      Score (SSS), and State-Trait Anxiety Inventory (STAI). RESULTS: Clinical scores
      were reduced significantly following therapy with five of the six clinical tests
      (FIQ, BFI, BDI, WPI, SSS; p < 0.05). Brain activation post-treatment was
      significantly lower than that pre-treatment in 13 regions of the brain (p <
      0.001). CONCLUSIONS: Our findings confirm that pregabalin influences aspects of
      the whole pain matrix, using fMRI, inducing longitudinal changes in neuronal
      activity during the pain state, and that it reduces pain and other core symptoms
      of FM. This method could be applied to other longitudinal clinical trials of
      pharmacological treatments for FM.

PMID- 24040179
TI  - NAD+-carrying mesoporous silica nanoparticles can prevent oxidative stress
      induced energy failures of both rodent astrocytes and PC12 cells.
AB  - AIM: To test the hypothesis that NAD(+)-carrying mesoporous silica nanoparticles
      (M-MSNs@NAD+) can effectively deliver NAD(+) into cells to produce cytoprotective
      effects. METHODS & MATERIALS: NAD(+) was incorporated into M-MSNs. Primary rat
      astrocyte cultures and PC12 cells were treated with H2O2, followed by post
      treatment with M-MSNs@NAD+. After various durations of the post-treatment,
      intracellular NAD(+) levels, intracellular ATP levels and lactate dehydrogenase
      (LDH) release were determined. RESULTS & DISCUSSION: M-MSNs can be effectively
      loaded with NAD(+). The M-MSNs@NAD+ can significantly attenuate H2O2-induced
      NAD(+) and ATP decreases in both astrocyte cultures and PC12 cells. M-MSNs@NAD+
      can also partially prevent the H2O2-induced LDH release from both astrocyte
      cultures and PC12 cells. In contrast, the NAD(+) that is spontaneously released
      from the M-MSNs@NAD+ is insufficient to prevent the H2O2-induced damage.
      CONCLUSIONS: Our study has suggested the first approach that can effectively
      deliver NAD(+) into cells, which provides an important basis both for elucidating
      the roles of intracellular NAD(+) in biological functions and for therapeutic
      applications of NAD(+). Our study has also provided the first direct evidence
      demonstrating a key role of NAD(+) depletion in oxidative stress-induced ATP
      decreases.

PMID- 24040180
TI  - Differential effects of allergen challenge on large and small airway reactivity
      in mice.
AB  - The relative contributions of large and small airways to hyperresponsiveness in
      asthma have yet to be fully assessed. This study used a mouse model of chronic
      allergic airways disease to induce inflammation and remodelling and determine
      whether in vivo hyperresponsiveness to methacholine is consistent with in vitro
      reactivity of trachea and small airways. Balb/C mice were sensitised (days 0, 14)
      and challenged (3 times/week, 6 weeks) with ovalbumin. Airway reactivity was
      compared with saline-challenged controls in vivo assessing whole lung resistance,
      and in vitro measuring the force of tracheal contraction and the magnitude/rate
      of small airway narrowing within lung slices. Increased airway inflammation,
      epithelial remodelling and fibrosis were evident following allergen challenge. In
      vivo hyperresponsiveness to methacholine was maintained in isolated trachea. In
      contrast, methacholine induced slower narrowing, with reduced potency in small
      airways compared to controls. In vitro incubation with IL-1/TNFalpha did not
      alter reactivity. The hyporesponsiveness to methacholine in small airways within
      lung slices following chronic ovalbumin challenge was unexpected, given
      hyperresponsiveness to the same agonist both in vivo and in vitro in tracheal
      preparations. This finding may reflect the altered interactions of small airways
      with surrounding parenchymal tissue after allergen challenge to oppose airway
      narrowing and closure. 

PMID- 24040181
TI  - Modified incision design for submental flap: an excellent design method for the
      reconstruction of a defect after head and neck tumor resection.
AB  - BACKGROUND: The usage of submental flap is a good method for head and neck
      reconstruction, but it has some risk also, such as anatomical variations and
      surgical errors. In this article, we present a modified incision design for the
      submental flap. METHODS: We designed a modified submental flap incision method
      based on the overlap of the incision outline of the submental flap, platysma
      myocutaneous flap and infrahyoid myocutaneous flap. If we found that the
      submental flap was unreliable during the neck dissection at the level III, II and
      Ib areas, the infrahyoid myocutaneous flap or platysma myocutaneous flap was used
      to replace it. Between 2004 and 2012, we performed 30 cases using this method. As
      control, 33 radial forearm free flaps were counted. Significant differences were
      evaluated using the chi(2) test and Mann-Whitney U. Survival and recurrence were
      analyzed using the Kaplan-Meier method. RESULTS: Of the 30 patients, 27 finally
      received a submental flap, 1 patient received an infrahyoid myocutaneous flap,
      and 2 patients received a platysma myocutaneous flap. In patients who received
      the submental flap, the average operation time was 5.9 hours, 2.4 hours shorter
      than the radial forearm free flap group; the average age was 61.8, 6.1 years
      older than the radial forearm free flap group; the survival time and recurrence
      time did not significantly differ with those of the forearm free flap group; and
      the success rate was higher than traditional methods. CONCLUSIONS: The wider
      indications, less required time, the similar low risk of recurrence and death as
      radial forearm free flap, higher success rate than traditional submental flap
      harvest methods, and ability to safely harvest a submental flap make the modified
      incision design a reliable method.

PMID- 24040182
TI  - The expression pattern of EVA1C, a novel Slit receptor, is consistent with an
      axon guidance role in the mouse nervous system.
AB  - The Slit/Robo axon guidance families play a vital role in the formation of neural
      circuitry within select regions of the developing mouse nervous system. Typically
      Slits signal through the Robo receptors, however they also have Robo-independent
      functions. The novel Slit receptor Eva-1, recently discovered in C. elegans, and
      the human orthologue of which is located in the Down syndrome critical region on
      chromosome 21, could account for some of these Robo independent functions as well
      as provide selectivity to Robo-mediated axon responses to Slit. Here we
      investigate the expression of the mammalian orthologue EVA1C in regions of the
      developing mouse nervous system which have been shown to exhibit Robo-dependent
      and -independent responses to Slit. We report that EVA1C is expressed by axons
      contributing to commissures, tracts and nerve pathways of the developing spinal
      cord and forebrain. Furthermore it is expressed by axons that display both Robo
      dependent and -independent functions of Slit, supporting a role for EVA1C in
      Slit/Robo mediated neural circuit formation in the developing nervous system. 

PMID- 24040183
TI  - The metabolic syndrome among postmenopausal women in rural Canton: prevalence,
      associated factors, and the optimal obesity and atherogenic indices.
AB  - OBJECTIVES: This research aimed to (i) determine the prevalence of metabolic
      syndrome (MetS) and its components; (ii) assess factors associated with MetS, and
      (iii) define optimal ethnic-specific cutoffs of obesity- and atherogenic-based
      markers to predict MetS among postmenopausal women in rural Canton.
      METHODOLOGY/PRINCIPAL FINDINGS: The Rural Canton Diabetes and Metabolic Disorders
      Study, a population based cross-sectional study, was conducted during 2011-2012
      in Canton. In person interviews, blood glucose and lipid measurements were
      completed for 4,706 postmenopausal women who did not receive hormone replacement
      therapy. MetS was diagnosed using criteria of the Joint-Interim-Statement (JIS),
      the International-Diabetes-Federation (IDF) and the Modified-Third-Adult
      Treatment-Panel (M-ATPIII). Age-standardized prevalence of MetS was 38.4%, 28.8%,
      and 37.1% according to JIS, IDF, and M-ATPIII criteria, respectively. Excellent
      agreement was observed between three definitions (kappa >= 0.79), in particular
      between JIS and ATPIII (kappa = 0.98, 95%CI: 0.97-0.98). Factors positively
      associated with MetS were living in Southern Canton, personal income, current
      smoking, higher BMI, and family history of cardiovascular disease. However,
      regular leisure-time physical activity can have protective effects. The optimal
      cutoff values for waist-circumference (WC), waist-to-hip ratio (WHR), waist-to
      height ratio(WHtR), BMI, HDL-cholesterol to total cholesterol ratio (HDL/TC), HDL
      cholesterol to LDL-cholesterol ratio (HDL/LDL), and triglyceride to HDL
      cholesterol ratio (TG/HDL) that predicted the presence of MetS were 79.5 cm,
      0.86, 0.53, 22.47 kg/m(2), 0.33, 0.68, and 0.88, respectively. CONCLUSIONS: This
      study highlights the importance of MetS among postmenopausal women in rural
      Canton. Our findings contribute to help selecting Cantonese-specific markers to
      predict MetS and support the need to establish educational program for promoting
      healthy-lifestyles among this population.

PMID- 24040184
TI  - CD146 deletion in the nervous system impairs appetite, locomotor activity and
      spatial learning in mice.
AB  - Cell adhesion molecules (CAMs) are crucial effectors for the development and
      maintenance of the nervous system. Mutations in human CAM genes are linked to
      brain disorders and psychological diseases, and CAM knockout mice always exhibit
      similar behavioral abnormalities. CD146 is a CAM of the immunoglobulin
      superfamily that interacts with Neurite Outgrowth Factor and involved in neurite
      extension in vitro. However, little is known about its in vivo function in the
      nervous system. In this study, we used a murine CD146 nervous system knockout
      (CD146(ns-ko)) model. We found that the brains of some CD146(ns-ko) mice were
      malformed with small olfactory bulbs. CD146(ns-ko) mice exhibited lower body
      weights and smaller food intake when compared with wild type littermates.
      Importantly, behavior tests revealed that CD146(ns-ko) mice exhibited significant
      decreased locomotor activity and impaired capacity for spatial learning and
      memory. Our results demonstrate that CD146 is important for mammalian nervous
      system development and proper behavior patterns. 

PMID- 24040185
TI  - Long-term effects of attentional performance on functional brain network
      topology.
AB  - Individuals differ in their cognitive resilience. Less resilient people
      demonstrate a greater tendency to vigilance decrements within sustained attention
      tasks. We hypothesized that a period of sustained attention is followed by
      prolonged changes in the organization of "resting state" brain networks and that
      individual differences in cognitive resilience are related to differences in post
      task network reorganization. We compared the topological and spatial properties
      of brain networks as derived from functional MRI data (N = 20) recorded for 6
      mins before and 12 mins after the performance of an attentional task. Furthermore
      we analysed changes in brain topology during task performance and during the
      switches between rest and task conditions. The cognitive resilience of each
      individual was quantified as the rate of increase in response latencies over the
      32-minute time course of the attentional paradigm. On average, functional
      networks measured immediately post-task demonstrated significant and prolonged
      changes in network organization compared to pre-task networks with higher
      connectivity strength, more clustering, less efficiency, and shorter distance
      connections. Individual differences in cognitive resilience were significantly
      correlated with differences in the degree of recovery of some network parameters.
      Changes in network measures were still present in less resilient individuals in
      the second half of the post-task period (i.e. 6-12 mins after task completion),
      while resilient individuals already demonstrated significant reductions of
      functional connectivity and clustering towards pre-task levels. During task
      performance brain topology became more integrated with less clustering and higher
      global efficiency, but linearly decreased with ongoing time-on-task. We conclude
      that sustained attentional task performance has prolonged, "hang-over" effects on
      the organization of post-task resting-state brain networks; and that more
      cognitively resilient individuals demonstrate faster rates of network recovery
      following a period of attentional effort.

PMID- 24040186
TI  - Relationship of serum interleukin-10 and its genetic variations with ischemic
      stroke in a Chinese general population.
AB  - BACKGROUND AND PURPOSE: Anti-inflammatory cytokine and its genetic variations may
      play an important role in the process of atherosclerosis. We assessed whether
      serum interleukin-10 (IL-10) and its genetic variations are associated with
      ischemic stroke in a Chinese general population. METHODS: An epidemiological
      survey on cardiovascular diseases and their risk factors was carried in a general
      population in Beijing in 2005. Serum IL-10, IL-6, p-selectin, soluble
      intercellular adhesion molecule-1 and C-reactive protein were analyzed using
      ELISA kits, while three IL-10 Single Nucleotide Polymorphisms (SNP) (rs1800872,
      rs1554286 and rs3021094) were genotyped in 1475 participants. RESULTS: A high
      serum IL-10 (top tertile) was significantly associated with ischemic stroke
      (multivariable adjusted odds ratio (OR) =0.50; 95%CI 0.31-0.81). Rs1800872 (AA
      vs. AC+CC genotype, OR=1.60; 1.06-2.39), rs1554286(TT vs. CT+CC genotype,
      OR=1.59; 1.06-2.39), and rs3021094 (CC/CA vs. AA genotype, OR=1.64; 1.04-2.60)
      were all significantly associated with ischemic stroke even after controlling for
      age, sex, smoking, systolic blood pressure, total cholesterol, glucose, body mass
      index and serum IL-10. The SNP score (a summary index of these SNPs) and IL-10
      (top tertile) together significantly improved the discriminative power in
      predicting ischemic stroke by 3.3% (95%CI: 0.2-6.4, p=0.0398) compared to
      predictions based on conventional risk factors alone. CONCLUSIONS: The lower
      serum IL-10 concentration and its selected genetic variations were significantly
      associated with an increased likelihood of ischemic stroke in this cross
      sectional study. Our results suggest that more prospective studies should be
      conducted to provide stronger evidence justifying the use of IL-10 and its SNPs
      as new biomarkers to identify a predisposition towards ischemic stroke.

PMID- 24040187
TI  - Modulation of DNA-induced damage and repair capacity in humans after dietary
      intervention with lutein-enriched fermented milk.
AB  - Dietary factors provide protection against several forms of DNA damage.
      Additionally, consumer demand for natural products favours the development of
      bioactive food ingredients with health benefits. Lutein is a promising
      biologically active component in the food industry. The EFSA Panel on Dietetic
      Products, Nutrition and Allergies considers that protection from oxidative damage
      may be a beneficial physiological effect but that a cause and effect relationship
      has not been established. Thus, our aim was to evaluate the safety and potential
      functional effect of a lutein-enriched milk product using the Comet Assay in
      order to analyze the baseline, the induced DNA-damage and the repair capacity in
      the lymphocytes of 10 healthy donors before and after the intake of the mentioned
      product. Our data suggest that the regular consumption of lutein-enriched
      fermented milk results in a significant increase in serum lutein levels and this
      change is associated with an improvement in the resistance of DNA to damage and
      the capacity of DNA repair in lymphocytes. Our results also support the lack of a
      genotoxic effect at the doses supplied as well as the absence of interactions and
      side effects on other nutritional and biochemicals markers. 

PMID- 24040188
TI  - Novel seed adaptations of a monocotyledon seagrass in the wavy sea.
AB  - Returning to the sea, just like invasion of land, has occurred in many groups of
      animals and plants. For flowering plants, traits adapted to the terrestrial
      environments have to change or adopt a new function to allow the plants to
      survive and prosper in the sea where water motion tends to rotate and move seeds.
      In this investigation, how seeds of the seagrass Thalassia hemprichii
      (Hydrocharitaceae), a common monocotyledon in the Indo-Pacific, adapt to the wavy
      environment was studied. Mature seeds were collected from Dongsha Atoll in South
      China Sea. The effects of light qualities on seed germination, the seed
      morphology, the unipolar distribution of starch granules in the endosperms and
      growth of root hair-like filamentous cells from basal surface of the seeds were
      all found to differ from those of terrestrial monocotyledons. Physiologically,
      germination of the seeds was stimulated by blue light rather than red light.
      Morphologically, the bell-shaped seeds coupled with the unipolar distribution of
      starch granules in the enlarged bases helped maintain their upright posture on
      the tidal seafloor. Growth of root hair-like filamentous cells from the basal
      surface of the seeds prior to primary root growth served to attach onto
      sediments, providing leverage and attachment required by the primary roots to
      insert into sediments. These filamentous cells grasped coral sand but not
      silicate sand, demonstrating a habitat preference of this species. 

PMID- 24040189
TI  - Weber's law, the magnitude effect and discrimination of sugar concentrations in
      nectar-feeding animals.
AB  - Weber's law quantifies the perception of difference between stimuli. For
      instance, it can explain why we are less likely to detect the removal of three
      nuts from a bowl if the bowl is full than if it is nearly empty. This is an
      example of the magnitude effect - the phenomenon that the subjective perception
      of a linear difference between a pair of stimuli progressively diminishes when
      the average magnitude of the stimuli increases. Although discrimination
      performances of both human and animal subjects in various sensory modalities
      exhibit the magnitude effect, results sometimes systematically deviate from the
      quantitative predictions based on Weber's law. An attempt to reformulate the law
      to better fit data from acoustic discrimination tasks has been dubbed the "near
      miss to Weber's law". Here, we tested the gustatory discrimination performance of
      nectar-feeding bats (Glossophaga soricina), in order to investigate whether the
      original version of Weber's law accurately predicts choice behavior in a two
      alternative forced choice task. As expected, bats either preferred the sweeter of
      the two options or showed no preference. In 4 out of 6 bats the near-miss to
      Weber's law provided a better fit and Weber's law underestimated the magnitude
      effect. In order to test the generality of this observation in nectar-feeders, we
      reviewed previously published data on bats, hummingbirds, honeybees, and
      bumblebees. In all groups of animals the near-miss to Weber's law provided better
      fits than Weber's law. Furthermore, whereas the magnitude effect was stronger
      than predicted by Weber's law in vertebrates, it was weaker than predicted in
      insects. Thus nectar-feeding vertebrates and insects seem to differ in how their
      choice behavior changes as sugar concentration is increased. We discuss the
      ecological and evolutionary implications of the observed patterns of sugar
      concentration discrimination. 

PMID- 24040190
TI  - MEG evidence for dynamic amygdala modulations by gaze and facial emotions.
AB  - BACKGROUND: Amygdala is a key brain region for face perception. While the role of
      amygdala in the perception of facial emotion and gaze has been extensively
      highlighted with fMRI, the unfolding in time of amydgala responses to emotional
      versus neutral faces with different gaze directions is scarcely known.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we addressed this question in healthy
      subjects using MEG combined with an original source imaging method based on
      individual amygdala volume segmentation and the localization of sources in the
      amygdala volume. We found an early peak of amygdala activity that was enhanced
      for fearful relative to neutral faces between 130 and 170 ms. The effect of
      emotion was again significant in a later time range (310-350 ms). Moreover, the
      amygdala response was greater for direct relative averted gaze between 190 and
      350 ms, and this effect was selective of fearful faces in the right amygdala.
      CONCLUSION: Altogether, our results show that the amygdala is involved in the
      processing and integration of emotion and gaze cues from faces in different time
      ranges, thus underlining its role in multiple stages of face perception.

PMID- 24040191
TI  - Immune cells in the normal ovary and spontaneous ovarian tumors in the laying hen
      (Gallus domesticus) model of human ovarian cancer.
AB  - BACKGROUND: Spontaneous ovarian cancer in chickens resembles human tumors both
      histologically and biochemically. The goal was to determine if there are
      differences in lymphocyte content between normal ovaries and ovarian tumors in
      chickens as a basis for further studies to understand the role of immunity in
      human ovarian cancer progression. METHODS: Hens were selected using grey scale
      and color Doppler ultrasound to determine if they had normal or tumor morphology.
      Cells were isolated from ovaries (n = 6 hens) and lymphocyte numbers were
      determined by flow cytometry using antibodies to avian CD4 and CD8 T and B (Bu1a)
      cells. Ovarian sections from another set of hens (n = 26) were assessed to verify
      tumor type and stage and to count CD4, CD8 and Bu1a immunostained cells by
      morphometric analysis. RESULTS: T and B cells were more numerous in ovarian
      tumors than in normal ovaries by flow cytometry and immunohistochemistry. There
      were less CD4+ cells than CD8+ and Bu1a+ cells in normal ovaries or ovarian
      tumors. CD8+ cells were the dominant T cell sub-type in both ovarian stroma and
      in ovarian follicles compared to CD4+ cells. Bu1a+ cells were consistently found
      in the stroma of normal ovaries and ovarian tumors but were not associated with
      follicles. The number of immune cells was highest in late stage serous tumors
      compared to endometrioid and mucinous tumors. CONCLUSIONS: The results suggest
      that similar to human ovarian cancer there are comparatively more immune cells in
      chicken ovarian tumors than in normal ovaries, and the highest immune cell
      content occurs in serous tumors. Thus, this study establishes a foundation for
      further study of tumor immune responses in a spontaneous model of ovarian cancer
      which will facilitate studies of the role of immunity in early ovarian cancer
      progression and use of the hen in pre-clinical vaccine trials.

PMID- 24040193
TI  - Energy reallocation to breeding performance through improved nest building in
      laboratory mice.
AB  - Mice are housed at temperatures (20-26  degrees C) that increase their basal
      metabolic rates and impose high energy demands to maintain core temperatures.
      Therefore, energy must be reallocated from other biological processes to increase
      heat production to offset heat loss. Supplying laboratory mice with nesting
      material may provide sufficient insulation to reduce heat loss and improve both
      feed conversion and breeding performance. Naive C57BL/6, BALB/c, and CD-1
      breeding pairs were provided with bedding alone, or bedding supplemented with
      either 8 g of Enviro-Dri, 8 g of Nestlets, for 6 months. Mice provided with
      either nesting material built more dome-like nests than controls. Nesting
      material improved feed efficiency per pup weaned as well as pup weaning weight.
      The breeding index (pups weaned/dam/week) was higher when either nesting material
      was provided. Thus, the sparing of energy for thermoregulation of mice given
      additional nesting material may have been responsible for the improved breeding
      and growth of offspring.

PMID- 24040192
TI  - The gustin (CA6) gene polymorphism, rs2274333 (A/G), as a mechanistic link
      between PROP tasting and fungiform taste papilla density and maintenance.
AB  - Taste sensitivity to PROP varies greatly among individuals and is associated with
      polymorphisms in the bitter receptor gene TAS2R38, and with differences in
      fungiform papilla density on the anterior tongue surface. Recently we showed that
      the PROP non-taster phenotype is strongly associated with the G variant of
      polymorphism rs2274333 (A/G) of the gene that controls the salivary trophic
      factor, gustin. The aims of this study were 1) to investigate the role of gustin
      gene polymorphism rs2274333 (A/G), in PROP sensitivity and fungiform papilla
      density and morphology, and 2) to investigate the effect of this gustin gene
      polymorphism on cell proliferation and metabolic activity. Sixty-four subjects
      were genotyped for both genes by PCR techniques, their PROP sensitivity was
      assessed by scaling and threshold methods, and their fungiform papilla density,
      diameter and morphology were determined. In vitro experiments examined cell
      proliferation and metabolic activity, following treatment with saliva of
      individuals with and without the gustin gene mutation, and with isolated protein,
      in the two iso-forms. Gustin and TAS2R38 genotypes were associated with PROP
      threshold (p=0.0001 and p=0.0042), but bitterness intensity was mostly determined
      by TAS2R38 genotypes (p<0.000001). Fungiform papillae densities were associated
      with both genotypes (p<0.014) (with a stronger effect for gustin; p=0.0006), but
      papilla morphology was a function of gustin alone (p<0.0012). Treatment of
      isolated cells with saliva from individuals with the AA form of gustin or direct
      application of the active iso-form of gustin protein increased cell proliferation
      and metabolic activity (p<0.0135). These novel findings suggest that the
      rs2274333 polymorphism of the gustin gene affects PROP sensitivity by acting on
      fungiform papilla development and maintenance, and could provide the first
      mechanistic explanation for why PROP super-tasters are more responsive to a broad
      range of oral stimuli. 

PMID- 24040194
TI  - Growth prior to thermogenesis for a quick fledging of Adelie penguin chicks
      (Pygoscelis adeliae).
AB  - The evolutionary trade-off between tissue growth and mature function restricts
      the post natal development of polar birds. The present study uses an original
      integrative approach as it includes gene expression, plus biochemical and
      physiological analysis to investigate how Adelie penguin chicks achieve a rapid
      growth despite the energetic constraints linked to the cold and the very short
      breeding season in Antarctica. In pectoralis muscle, the main thermogenic tissue
      in birds, our data show that the transition from ectothermy to endothermy on Day
      15 post- hatching is associated with substantial and coordinated changes in the
      transcription of key genes. While the early activation of genes controlling cell
      growth and differentiation (avGHR, avIGF-1R, T3Rbeta) is rapidly down-regulated
      after hatching, the global increase in the relative expression of genes involved
      in thermoregulation (avUCP, avANT, avLPL) and transcriptional regulation
      (avPGC1alpha, avT3Rbeta) underlie the muscular acquisition of oxidative
      metabolism. Adelie chicks only become real endotherms at 15 days of age with the
      development of an oxidative muscle phenotype and the ability to shiver
      efficiently. The persistent muscular expression of IGF-1 throughout growth
      probably acts as a local mediator to adjust muscle size and its oxidative
      capacity to anticipate the new physiological demands of future Dives in cold
      water. The up-regulation of T3Rbeta mRNA levels suggests that circulating T3 may
      play an important role in the late maturation of skeletal muscle by reinforcing,
      at least in part, the paracrine action of IGF-1. From day 30, the metabolic shift
      from mixed substrate to lipid metabolism, with the markedly increased mRNA levels
      of muscle avLPL, avANT and avUCP, suggests the late development of a fatty acid
      enhanced muscle non-shivering thermogenesis mechanism. This molecular control is
      the key to this finely-tuned strategy by which the Adelie penguin chick
      successfully heads for the sea on schedule. 

PMID- 24040195
TI  - Aspirin and low-molecular weight heparin combination therapy effectively prevents
      recurrent miscarriage in hyperhomocysteinemic women.
AB  - The management of recurrent pregnancy loss (RPL) still remains a great challenge,
      and women with polycystic ovarian syndrome (PCOS) are at a greater risk for
      spontaneous abortion. Treatment with low-molecular-weight heparin (LMWH) has
      become an accepted treatment option for women with RPL; however, the subgroup of
      women, who are likely to respond to LMWH, has not been precisely identified. The
      present study evaluated the efficacy of LMWH with reference to PCOS and
      associated metabolic phenotypes including hyperhomocysteinemia (HHcy), insulin
      resistance (IR) and obesity. This prospective observational study was conducted
      at Institute of Reproductive Medicine, Kolkata, India. A total of 967 women with
      history of 2 or more consecutive first trimester abortions were screened and 336
      were selected for the study. The selected patients were initially divided on the
      basis of presence or absence of PCOS, while subsequent stratification was based
      on HHcy, IR and/or obesity. The subjects had treatment with aspirin during one
      conception cycle and aspirin-LMWH combined anticoagulant therapy for the
      immediate next conception cycle, if the first treated cycle was unsuccessful.
      Pregnancy salvage was the sole outcome measure. The overall rate of pregnancy
      salvage following aspirin therapy was 43.15%, which was mostly represented by
      normohomocysteinemic women, while the salvage rate was lower in the HHcy
      populations irrespective of the presence or absence of PCOS, IR, or obesity. By
      contrast, aspirin-LMWH combined therapy could rescue 66.84% pregnancies in the
      aspirin-failed cases. Logistic regression analyses showed that HHcy remained a
      significant factor in predicting salvage rates in the PCOS, IR, and obese
      subpopulations controlled for other confounding factors. With regard to pregnancy
      salvage, combined anticoagulant therapy with aspirin and LMWH conferred added
      benefit to those with HHcy phenotype. 

PMID- 24040196
TI  - Mitochondrial haplotypes associated with biomarkers for Alzheimer's disease.
AB  - Various studies have suggested that the mitochondrial genome plays a role in late
      onset Alzheimer's disease, although results are mixed. We used an endophenotype
      based approach to further characterize mitochondrial genetic variation and its
      relationship to risk markers for Alzheimer's disease. We analyzed longitudinal
      data from non-demented, mild cognitive impairment, and late-onset Alzheimer's
      disease participants in the Alzheimer's Disease Neuroimaging Initiative with
      genetic, brain imaging, and behavioral data. We assessed the relationship of
      structural MRI and cognitive biomarkers with mitochondrial genome variation using
      TreeScanning, a haplotype-based approach that concentrates statistical power by
      analyzing evolutionarily meaningful groups (or clades) of haplotypes together for
      association with a phenotype. Four clades were associated with three different
      endophenotypes: whole brain volume, percent change in temporal pole thickness,
      and left hippocampal atrophy over two years. This is the first study of its kind
      to identify mitochondrial variation associated with brain imaging endophenotypes
      of Alzheimer's disease. Our results provide additional evidence that the
      mitochondrial genome plays a role in risk for Alzheimer's disease. 

PMID- 24040197
TI  - The POZ-ZF transcription factor Kaiso (ZBTB33) induces inflammation and
      progenitor cell differentiation in the murine intestine.
AB  - Since its discovery, several studies have implicated the POZ-ZF protein Kaiso in
      both developmental and tumorigenic processes. However, most of the information
      regarding Kaiso's function to date has been gleaned from studies in Xenopus
      laevis embryos and mammalian cultured cells. To examine Kaiso's role in a
      relevant, mammalian organ-specific context, we generated and characterized a
      Kaiso transgenic mouse expressing a murine Kaiso transgene under the control of
      the intestine-specific villin promoter. Kaiso transgenic mice were viable and
      fertile but pathological examination of the small intestine revealed distinct
      morphological changes. Kaiso transgenics (Kaiso(Tg/+)) exhibited a crypt
      expansion phenotype that was accompanied by increased differentiation of
      epithelial progenitor cells into secretory cell lineages; this was evidenced by
      increased cell populations expressing Goblet, Paneth and enteroendocrine markers.
      Paradoxically however, enhanced differentiation in Kaiso(Tg/+) was accompanied by
      reduced proliferation, a phenotype reminiscent of Notch inhibition. Indeed,
      expression of the Notch signalling target HES-1 was decreased in Kaiso(Tg/+)
      animals. Finally, our Kaiso transgenics exhibited several hallmarks of
      inflammation, including increased neutrophil infiltration and activation, villi
      fusion and crypt hyperplasia. Interestingly, the Kaiso binding partner and
      emerging anti-inflammatory mediator p120(ctn) is recruited to the nucleus in
      Kaiso(Tg/+) mice intestinal cells suggesting that Kaiso may elicit inflammation
      by antagonizing p120(ctn) function.

PMID- 24040198
TI  - Non-catalytic site HIV-1 integrase inhibitors disrupt core maturation and induce
      a reverse transcription block in target cells.
AB  - HIV-1 integrase (IN) is the target for two classes of antiretrovirals: i) the
      integrase strand-transfer inhibitors (INSTIs) and ii) the non-catalytic site
      integrase inhibitors (NCINIs). NCINIs bind at the IN dimer interface and are
      thought to interfere primarily with viral DNA (vDNA) integration in the target
      cell by blocking IN-vDNA assembly as well as the IN-LEDGF/p75 interaction. Herein
      we show that treatment of virus-producing cells, but not of mature virions or
      target cells, drives NCINI antiviral potency. NCINIs target an essential late
      stage event in HIV replication that is insensitive to LEDGF levels in the
      producer cells. Virus particles produced in the presence of NCINIs displayed
      normal Gag-Pol processing and endogenous reverse transcriptase activity, but were
      defective at initiating vDNA synthesis following entry into the target cell.
      NCINI-resistant virus carrying a T174I mutation in the IN dimer interface was
      less sensitive to the compound-induced late-stage effects, including the reverse
      transcription block. Wild-type, but not T174I virus, produced in the presence of
      NCINIs exhibited striking defects in core morphology and an increased level of IN
      oligomers that was not observed upon treatment of mature cell-free particles.
      Collectively, these results reveal that NCINIs act through a novel mechanism that
      is unrelated to the previously observed inhibition of IN activity or IN-LEDGF
      interaction, and instead involves the disruption of an IN function during HIV-1
      core maturation and assembly. 

PMID- 24040200
TI  - Very early passive cycling exercise in mechanically ventilated critically ill
      patients: physiological and safety aspects--a case series.
AB  - INTRODUCTION: Early mobilization can be performed in critically ill patients and
      improves outcomes. A daily cycling exercise started from day 5 after ICU
      admission is feasible and can enhance functional capacity after hospital
      discharge. In the present study we verified the physiological changes and safety
      of an earlier cycling intervention (< 72 hrs of mechanical ventilation) in
      critical ill patients. METHODS: Nineteen hemodynamically stable and deeply
      sedated patients within the first 72 hrs of mechanical ventilation were enrolled
      in a single 20 minute passive leg cycling exercise using an electric cycle
      ergometer. A minute-by-minute evaluation of hemodynamic, respiratory and
      metabolic variables was undertaken before, during and after the exercise.
      Analyzed variables included the following: cardiac output, systemic vascular
      resistance, central venous blood oxygen saturation, respiratory rate and tidal
      volume, oxygen consumption, carbon dioxide production and blood lactate levels.
      RESULTS: We enrolled 19 patients (42% male, age 55 +/- 17 years, SOFA = 6 +/- 3,
      SAPS3 score = 58 +/- 13, PaO2/FIO2 = 223 +/- 75). The median time of mechanical
      ventilation was 1 day (02), and 68% (n=13) of our patients required
      norepinephrine (maximum concentration = 0.47 ug.kg(-1).min(-1)). There were no
      clinically relevant changes in any of the analyzed variables during the exercise,
      and two minor adverse events unrelated to hemodynamic instability were observed.
      CONCLUSIONS: In our study, this very early passive cycling exercise in sedated,
      critically ill, mechanically ventilated patients was considered safe and was not
      associated with significant alterations in hemodynamic, respiratory or metabolic
      variables even in those requiring vasoactive agents.

PMID- 24040199
TI  - Spatiotemporal dynamics and epistatic interaction sites in dengue virus type 1: a
      comprehensive sequence-based analysis.
AB  - The continuing threat of dengue fever necessitates a comprehensive
      characterisation of its epidemiological trends. Phylogenetic and recombination
      events were reconstructed based on 100 worldwide dengue virus (DENV) type 1
      genome sequences with an outgroup (prototypes of DENV2-4). The phylodynamic
      characteristics and site-specific variation were then analysed using data without
      the outgroup. Five genotypes (GI-GV) and a ladder-like structure with short
      terminal branch topology were observed in this study. Apparently, the
      transmission of DENV1 was geographically random before gradual localising with
      human activity as GI-GIII in South Asia, GIV in the South Pacific, and GV in the
      Americas. Genotypes IV and V have recently shown higher population densities
      compared to older genotypes. All codon regions and all tree branches were skewed
      toward a negative selection, which indicated that their variation was restricted
      by protein function. Notably, multi-epistatic interaction sites were found in
      both PrM 221 and NS3 1730. Recombination events accumulated in regions E, NS3
      NS4A, and particularly in region NS5. The estimated coevolution pattern also
      highlights the need for further study of the biological role of protein PrM 221
      and NS3 1730. The recent transmission of emergent GV sublineages into Central
      America and Europe mandates closely monitoring of genotype interaction and
      succession. 

PMID- 24040201
TI  - Gymnemic acids inhibit hyphal growth and virulence in Candida albicans.
AB  - Candida albicans is an opportunistic and polymorphic fungal pathogen that causes
      mucosal, disseminated and invasive infections in humans. Transition from the
      yeast form to the hyphal form is one of the key virulence factors in C. albicans
      contributing to macrophage evasion, tissue invasion and biofilm formation.
      Nontoxic small molecules that inhibit C. albicans yeast-to-hypha conversion and
      hyphal growth could represent a valuable source for understanding pathogenic
      fungal morphogenesis, identifying drug targets and serving as templates for the
      development of novel antifungal agents. Here, we have identified the triterpenoid
      saponin family of gymnemic acids (GAs) as inhibitor of C. albicans morphogenesis.
      GAs were isolated and purified from Gymnema sylvestre leaves, the Ayurvedic
      traditional medicinal plant used to treat diabetes. Purified GAs had no effect on
      the growth and viability of C. albicans yeast cells but inhibited its yeast-to
      hypha conversion under several hypha-inducing conditions, including the presence
      of serum. Moreover, GAs promoted the conversion of C. albicans hyphae into yeast
      cells under hypha inducing conditions. They also inhibited conidial germination
      and hyphal growth of Aspergillus sp. Finally, GAs inhibited the formation of
      invasive hyphae from C. albicans-infected Caenorhabditis elegans worms and
      rescued them from killing by C. albicans. Hence, GAs could be useful for various
      antifungal applications due to their traditional use in herbal medicine. 

PMID- 24040202
TI  - Systems-based identification of temporal processing pathways during bone cell
      mechanotransduction.
AB  - Bone has long been established to be a highly mechanosensitive tissue. When
      subjected to mechanical loading, bone exhibits profoundly different anabolic
      responses depending on the temporal pattern in which the stimulus is applied.
      This phenomenon has been termed temporal processing, and involves complex signal
      amplification mechanisms that are largely unidentified. In this study, our goal
      was to characterize transcriptomic perturbations arising from the insertion of
      intermittent rest periods (a temporal variation with profound effects on bone
      anabolism) in osteoblastic cells subjected to fluid flow, and assess the utility
      of these perturbations to identify signaling pathways that are differentially
      activated by this temporal variation. At the level of the genome, we found that
      the common and differential alterations in gene expression arising from the two
      flow conditions were distributionally distinct, with the differential alterations
      characterized by many small changes in a large number of genes. Using
      bioinformatics analysis, we identified distinct up- and down-regulation
      transcriptomic signatures associated with the insertion of rest intervals, and
      found that the up-regulation signature was significantly associated with MAPK
      signaling. Confirming the involvement of the MAPK pathway, we found that the
      insertion of rest intervals significantly elevated flow-induced p-ERK1/2 levels
      by enabling a second spike in activity that was not observed in response to
      continuous flow. Collectively, these studies are the first to characterize
      distinct transcriptomic perturbations in bone cells subjected to continuous and
      intermittent stimulation, and directly demonstrate the utility of systems-based
      transcriptomic analysis to identify novel acute signaling pathways underlying
      temporal processing in bone cells. 

PMID- 24040203
TI  - In vivo noninvasive detection of Brown Adipose Tissue through intermolecular zero
      quantum MRI.
AB  - The recent discovery of active Brown Adipose Tissue (BAT) in adult humans has
      opened new avenues for obesity research and treatment, as reduced BAT activity
      seem to be implicated in human energy imbalance, diabetes, and hypertension.
      However, clinical applications are currently limited by the lack of non-invasive
      tools for measuring mass and function of this tissue in humans. Here we present a
      new magnetic resonance imaging method based on the normally invisible
      intermolecular multiple-quantum coherence (1)H MR signal. This method, which
      doesn't require special hardware modifications, can be used to overcome partial
      volume effect, the major limitation of MR-based approaches that are currently
      being investigated for the detection of BAT in humans. With this method we can
      exploit the characteristic cellular structure of BAT to selectively image it,
      even when (as in humans) it is intimately mixed with other tissues. We
      demonstrate and validate this method in mice using PET scans and histology. We
      compare this methodology with conventional (1)H MR fat fraction methods. Finally,
      we investigate its feasibility for the detection of BAT in humans. 

PMID- 24040205
TI  - Increased methylglyoxal formation with upregulation of renin angiotensin system
      in fructose fed Sprague Dawley rats.
AB  - The current epidemic of obesity and type 2 diabetes is attributed to a high
      carbohydrate diet, containing mainly high fructose corn syrup and sucrose. More
      than two thirds of diabetic patients have hypertension. Methylglyoxal is a highly
      reactive dicarbonyl generated during glucose and fructose metabolism, and a major
      precursor of advanced glycation end products (AGEs). Plasma methylglyoxal levels
      are increased in hypertensive rats and diabetic patients. Our aim was to examine
      the levels of methylglyoxal, mediators of the renin angiotensin system and blood
      pressure in male Sprague-Dawley rats treated with a high fructose diet (60% of
      total calories) for 4 months. The thoracic aorta and kidney were used for
      molecular studies, along with cultured vascular smooth muscle cells (VSMCs).
      HPLC, Western blotting and Q-PCR were used to measure methylglyoxal and reduced
      glutathione (GSH), proteins and mRNA, respectively. Fructose treated rats
      developed a significant increase in blood pressure. Methylglyoxal level and
      protein and mRNA for angiotensin II, AT1 receptor, adrenergic alpha1D receptor
      and renin were significantly increased, whereas GSH levels were decreased, in the
      aorta and/or kidney of fructose fed rats. The protein expression of the receptor
      for AGEs (RAGE) and NF-kappaB were also significantly increased in the aorta of
      fructose fed rats. MG treated VSMCs showed increased protein for angiotensin II,
      AT1 receptor, and alpha1D receptor. The effects of methylglyoxal were attenuated
      by metformin, a methylglyoxal scavenger and AGEs inhibitor. In conclusion, we
      report a strong association between elevated levels of methylglyoxal, RAGE, NF
      kappaB, mediators of the renin angiotensin system and blood pressure in high
      fructose diet fed rats. 

PMID- 24040204
TI  - TRAIL-deficiency accelerates vascular calcification in atherosclerosis via
      modulation of RANKL.
AB  - The osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand
      (RANKL) cytokine system, not only controls bone homeostasis, but has been
      implicated in regulating vascular calcification. TNF-related apoptosis-inducing
      ligand (TRAIL) is a second ligand for OPG, and although its effect in vascular
      calcification in vitro is controversial, its role in vivo is not yet established.
      This study aimed to investigate the role of TRAIL in vascular calcification in
      vitro using vascular smooth muscle cells (VSMCs) isolated from TRAIL(-/-) and
      wild-type mice, as well as in vivo, in advanced atherosclerotic lesions of TRAIL(
      /-)ApoE(-/-) mice. The involvement of OPG and RANKL in this process was also
      examined. TRAIL dose-dependently inhibited calcium-induced calcification of human
      VSMCs, while TRAIL(-/-) VSMCs demonstrated accelerated calcification induced by
      multiple concentrations of calcium compared to wild-type cells. Consistent with
      this, RANKL mRNA was significantly elevated with 24 h calcium treatment, while
      OPG and TRAIL expression in human VSMCs was inhibited. Brachiocephalic arteries
      from TRAIL(-/-)ApoE(-/-) and ApoE(-/-) mice fed a high fat diet for 12 w
      demonstrated increased chondrocyte-like cells in atherosclerotic plaque, as well
      as increased aortic collagen II mRNA expression in TRAIL(-/-)ApoE(-/-) mice, with
      significant increases in calcification observed at 20 w. TRAIL(-/-)ApoE(-/-)
      aortas also had significantly elevated RANKL, BMP-2, IL-1beta, and PPAR-gamma
      expression at 12 w. Our data provides the first evidence that TRAIL deficiency
      results in accelerated cartilaginous metaplasia and calcification in
      atherosclerosis, and that TRAIL plays an important role in the regulation of
      RANKL and inflammatory markers mediating bone turn over in the vasculature. 

PMID- 24040206
TI  - The carboxyl-terminal amino acids render pro-human LC3B migration similar to
      lipidated LC3B in SDS-PAGE.
AB  - LC3 is widely used marker for macroautophagy assays. After translation pro-LC3 is
      processed by Atg4 to expose C-terminal glycine residue for downstream conjugation
      reactions to accomplish the conversion of LC3-I to LC3-II. SDS-PAGE based Western
      blot (Wb) is generally utilized to quantify LC3-II levels where the LC3-I band
      migrates slower than LC3-II. We found that pro-human LC3B migrated at similar
      rate as LC3B-II in SDS-PAGE. The carboxyl-terminal five amino acids, particularly
      Lysine(122) and Leucine(123) of human LC3B play a major role in the faster
      migration of unprocessed LC3B, rendering it indistinguishable from LC3B-II in Wb
      assays. The unique faster migration of unprocessed LC3B than LC3B-I is also
      revealed in mouse LC3B, rat LC3B and rat LC3 but not in human LC3C. Our findings
      for the first time define pro-LC3 migration patterns for LC3 family member from
      human, mouse and rat species in SDS-PAGE. These findings provide a reference for
      pro-LC3 band patterns when Atg4 function is inhibited. 

PMID- 24040207
TI  - Isn't it ironic? Neural correlates of irony comprehension in schizophrenia.
AB  - Ironic remarks are frequent in everyday language and represent an important form
      of social cognition. Increasing evidence indicates a deficit in comprehension in
      schizophrenia. Several models for defective comprehension have been proposed,
      including possible roles of the medial prefrontal lobe, default mode network,
      inferior frontal gyri, mirror neurons, right cerebral hemisphere and a possible
      mediating role of schizotypal personality traits. We investigated the neural
      correlates of irony comprehension in schizophrenia by using event-related
      functional magnetic resonance imaging (fMRI). In a prosody-free reading paradigm,
      15 female patients with schizophrenia and 15 healthy female controls silently
      read ironic and literal text vignettes during fMRI. Each text vignette ended in
      either an ironic (n = 22) or literal (n = 22) statement. Ironic and literal text
      vignettes were matched for word frequency, length, grammatical complexity, and
      syntax. After fMRI, the subjects performed an off-line test to detect error rate.
      In this test, the subjects indicated by button press whether the target sentence
      has ironic, literal, or meaningless content. Schizotypal personality traits were
      assessed using the German version of the schizotypal personality questionnaire
      (SPQ). Patients with schizophrenia made significantly more errors than did the
      controls (correct answers, 85.3% vs. 96.3%) on a behavioural level. Patients
      showed attenuated blood oxygen level-dependent (BOLD) response during irony
      comprehension mainly in right hemisphere temporal regions (ironic>literal
      contrast) and in posterior medial prefrontal and left anterior insula regions
      (for ironic>visual baseline, but not for literal>visual baseline). In patients
      with schizophrenia, the parahippocampal gyrus showed increased activation. Across
      all subjects, BOLD response in the medial prefrontal area was negatively
      correlated with the SPQ score. These results highlight the role of the posterior
      medial prefrontal and right temporal regions in defective irony comprehension in
      schizophrenia and the mediating role of schizotypal personality traits.

PMID- 24040208
TI  - Identification of potential cytokine pathways for therapeutic intervention in
      murine primary biliary cirrhosis.
AB  - Primary biliary cirrhosis (PBC) is considered a model autoimmune disease, with
      the most highly directed and specific autoantibody in both murine and human
      autoimmunity, the anti-mitochondrial autoantibody (AMA). However, therapeutic
      advances in this disease have lagged behind. Herein we have taken advantage of
      our unique model of murine PBC in which mice immunized with 2-octynoic acid
      coupled to BSA (2OA-BSA), a compound identified by quantitative structure
      activity relationships (QSAR) of human AMA binding, develop an intense
      inflammatory cholangitis with striking similarities to humans with PBC. In
      particular, we have constructed several unique gene-deleted mice, including mice
      deleted of IL-12p40, IL-12p35, IFN-gamma, IL-23p19, IL-17A, IL-17F and IL-22,
      immunized these animals with 2OA-BSA and followed the natural history of
      immunopathology to identify key pathways that might provide clues for successful
      therapy. Our data indicate that whereas both IL-12/Th1 and IL-23/Th17 are
      involved in cholangitis, it is the IL-12/Th1 signaling pathway that elicits
      pathology. In fact, deletion of IFN-gamma prevents disease and suppresses
      autoantibodies. Importantly, deletion of the Th17 cytokines IL-17A and IL-22, but
      not IL-17F, reduces biliary damage; IL-17A-knockout mice have reduced levels of
      anti-mitochondrial antibody. We further demonstrate that the production of IFN
      gamma is significantly decreased in the liver of IL-23p19(-/-), IL-17A(-/-) and
      IL-22(-/-) mice compared with controls. However, the ability of T cells to
      produce IFN-gamma was not affected in Th17 cytokine-deficient mice. Our data
      indicate that a deficient Th17 pathway suppresses the accumulation of IFN-gamma
      producing cells in liver during the early phase of cholangitis. In conclusion,
      whereas IFN-gamma has a pivotal role in the early events involved in the
      pathogenesis of autoimmune cholangitis induced by 2OA-BSA, the IL-23/Th17 pathway
      potentiates the effects of IL-12/IFN-gamma-mediated immunopathology. 

PMID- 24040209
TI  - Association between physical activity levels and physiological factors underlying
      mobility in young, middle-aged and older individuals living in a city district.
AB  - Maintaining adequate levels of physical activity is known to preserve health
      status and functional independence as individuals grow older. However, the
      relationship between determinants of physical activity (volume and intensity) and
      physiological factors underlying mobility (cardio-respiratory fitness,
      neuromuscular function and functional abilities) is still unclear. The aim of
      this study was to investigate the association between objectively quantified
      physical activity and a spectrum of physiological factors underlying mobility in
      young, middle-aged and older individuals living in a city district. Experiments
      were carried out on 24 young (28 +/- 2 years), 24 middle-aged (48 +/- 2 years)
      and 24 older (70 +/- 3 years) gender-matched volunteers. Physical activity was
      monitored by a wearable activity monitor to quantify volume and intensity of
      overall physical activity and selected habitual activities over 24 hours.
      Ventilatory threshold was assessed during an incremental cycling test. Torque,
      muscle fiber conduction velocity and agonist-antagonist coactivation were
      measured during maximal voluntary contraction of knee extensors and flexors.
      Ground reaction forces were measured during sit-to-stand and counter-movement
      jump. K-means cluster analysis was used to classify the participants' physical
      activity levels based on parameters of volume and intensity. Two clusters of
      physical activity volume (i.e., high and low volume) and three clusters of
      physical activity intensity (i.e. high, medium and low intensity) were identified
      in all participants. Cardio-respiratory fitness was associated with volume of
      overall physical activity as well as lying, sitting, standing, walking and stair
      climbing. On the other hand, neuromuscular function and functional abilities
      showed a significant association with intensity of overall physical activity as
      well as postural transition, walking and stair climbing. As a practical
      application, the relative role played by volume and intensity of overall physical
      activity and selected habitual activities should be taken into account in the
      design of preventative training interventions to preserve mobility as individuals
      grow older.

PMID- 24040210
TI  - Changing malaria transmission and implications in China towards National Malaria
      Elimination Programme between 2010 and 2012.
AB  - BACKGROUND: Towards the implementation of national malaria elimination programme
      in China since 2010, the epidemiology of malaria has changed dramatically, and
      the lowest malaria burden was achieved yearly. It is time to analyze the changes
      of malaria situation based on surveillance data from 2010 to 2012 to reconsider
      the strategies for malaria elimination. METHODS AND PRINCIPAL FINDINGS: Malaria
      epidemiological data was extracted from the provincial annual reports in China
      between 2010 and 2012. The trends of the general, autochthonous and imported
      malaria were analyzed, and epidemic areas were reclassified according to Action
      Plan of China Malaria Elimination (2010-2020). As a result, there reported 2743
      malaria cases with a continued decline in 2012, and around 7% autochthonous
      malaria cases accounted. Three hundred and fifty-three individual counties from
      19 provincial regions had autochthonous malaria between 2010 and 2012, and only
      one county was reclassified into Type I (local infections detected in 3
      consecutive years and the annual incidences >= 1/10,000) again. However, the
      imported malaria cases reported of each year were widespread, and 598 counties in
      29 provinces were suffered in 2012. CONCLUSIONS/SIGNIFICANCE: Malaria was reduced
      significantly from 2010 to 2012 in China, and malaria importation became an
      increasing challenge. It is necessary to adjust or update the interventions for
      subsequent malaria elimination planning and resource allocation.

PMID- 24040211
TI  - Regulation of sleep by neuropeptide Y-like system in Drosophila melanogaster.
AB  - Sleep is important for maintenance of normal physiology in animals. In mammals,
      neuropeptide Y (NPY), a homolog of Drosophila neuropeptide F (NPF), is involved
      in sleep regulation, with different effects in human and rat. However, the
      function of NPF on sleep in Drosophila melanogaster has not yet been described.
      In this study, we investigated the effects of NPF and its receptor-neuropeptide F
      receptor (NPFR1) on Drosophila sleep. Male flies over-expressing NPF or NPFR1
      exhibited increased sleep during the nighttime. Further analysis demonstrated
      that sleep episode duration during nighttime was greatly increased and sleep
      latency was significantly reduced, indicating that NPF and NPFR1 promote sleep
      quality, and their action on sleep is not because of an impact of the NPF signal
      system on development. Moreover, the homeostatic regulation of flies after sleep
      deprivation was disrupted by altered NPF signaling, since sleep deprivation
      decreased transcription of NPF in control flies, and there were less sleep loss
      during sleep deprivation and less sleep gain after sleep deprivation in flies
      overexpressing NPF and NPFR1 than in control flies, suggesting that NPF system
      auto-regulation plays an important role in sleep homeostasis. However, these
      effects did not occur in females, suggesting a sex-dependent regulatory function
      in sleep for NPF and NPFR1. NPF in D1 brain neurons showed male-specific
      expression, providing the cellular locus for male-specific regulation of sleep by
      NPF and NPFR1. This study brings a new understanding into sleep studies of a
      sexually dimorphic regulatory mode in female and male flies. 

PMID- 24040212
TI  - A test for pre-adapted phenotypic plasticity in the invasive tree Acer negundo L.
AB  - Phenotypic plasticity is a key mechanism associated with the spread of exotic
      plants and previous studies have found that invasive species are generally more
      plastic than co-occurring species. Comparatively, the evolution of phenotypic
      plasticity in plant invasion has received less attention, and in particular, the
      genetic basis of plasticity is largely unexamined. Native from North America,
      Acer negundo L. is aggressively impacting the riparian forests of southern and
      eastern Europe thanks to higher plasticity relative to co-occurring native
      species. We therefore tested here whether invasive populations have evolved
      increased plasticity since introduction. The performance of 1152 seedlings from 8
      native and 8 invasive populations was compared in response to nutrient
      availability. Irrespective of nutrients, invasive populations had higher growth
      and greater allocation to above-ground biomass relative to their native
      conspecifics. More importantly, invasive genotypes did not show increased
      plasticity in any of the 20 traits examined. This result suggests that the high
      magnitude of plasticity to nutrient variation of invasive seedlings might be pre
      adapted in the native range. Invasiveness of A. negundo could be explained by
      higher mean values of traits due to genetic differentiation rather than by
      evolution of increased plasticity. 

PMID- 24040213
TI  - C2-phytoceramide perturbs lipid rafts and cell integrity in Saccharomyces
      cerevisiae in a sterol-dependent manner.
AB  - Specific ceramides are key regulators of cell fate, and extensive studies aimed
      to develop therapies based on ceramide-induced cell death. However, the
      mechanisms regulating ceramide cytotoxicity are not yet fully elucidated. Since
      ceramides also regulate growth and stress responses in yeast, we studied how
      different exogenous ceramides affect yeast cells. C2-phytoceramide, a soluble
      form of phytoceramides, the yeast counterparts of mammalian ceramides, greatly
      reduced clonogenic survival, particularly in the G2/M phase, but did not induce
      autophagy nor increase apoptotic markers. Rather, the loss of clonogenic survival
      was associated with PI positive staining, disorganization of lipid rafts and cell
      wall weakening. Sensitivity to C2-phytoceramide was exacerbated in mutants
      lacking Hog1p, the MAP kinase homolog of human p38 kinase. Decreasing sterol
      membrane content reduced sensitivity to C2-phytoceramide, suggesting sterols are
      the targets of this compound. This study identified a new function of C2
      phytoceramide through disorganization of lipid rafts and induction of a necrotic
      cell death under hypo-osmotic conditions. Since lipid rafts are important in
      mammalian cell signaling and adhesion, our findings further support pursuing the
      exploitation of yeast to understand the basis of synthetic ceramides'
      cytotoxicity to provide novel strategies for therapeutic intervention in cancer
      and other diseases. 

PMID- 24040214
TI  - Early troponin T and prediction of potentially correctable in-hospital
      complications after coronary artery bypass grafting surgery.
AB  - BACKGROUND: Peak levels of troponin T (TnT) reliably predict morbidity and
      mortality after cardiac surgery. However, the therapeutic window to manage CABG
      related in-hospital complications may close before the peak is reached. We
      investigated whether early TnT levels correlate as well with complications after
      coronary artery bypass grafting (CABG) surgery. METHODS: A 12 month consecutive
      series of patients undergoing elective isolated CABG procedures (mini-extra
      corporeal circuit, Cardioplegic arrest) was analyzed. Logistic regression
      modeling was used to investigate whether TnT levels 6 to 8 hours after surgery
      were independently associated with in-hospital complications (either post
      operative myocardial infarction, stroke, new-onset renal insufficiency, intensive
      care unit (ICU) readmission, prolonged ICU stay (>48 hours), prolonged need for
      vasopressors (>24 hours), resuscitation or death). RESULTS: A total of 290
      patients, including 36 patients with complications, was analyzed. Early TnT
      levels (odds ratio (OR): 6.8, 95% confidence interval (CI): 2.2-21.4, P=.001),
      logistic EuroSCORE (OR: 1.2, 95%CI: 1.0-1.3, P=.007) and the need for
      vasopressors during the first 6 postoperative hours (OR: 2.7, 95%CI: 1.0-7.1,
      P=.05) were independently associated with the risk of complications. With
      consideration of vasopressor use during the first 6 postoperative hours, the sum
      of specificity (0.958) and sensitivity (0.417) of TnT for subsequent
      complications was highest at a TnT cut-off value of 0.8 ng/mL. CONCLUSION: Early
      TnT levels may be useful to guide ICU management of CABG patients. They predict
      clinically relevant complications within a potential therapeutic window,
      particularly in patients requiring vasopressors during the first postoperative
      hours, although with only moderate sensitivity.

PMID- 24040215
TI  - Prion protein accumulation in lipid rafts of mouse aging brain.
AB  - The cellular form of the prion protein (PrP(C)) is a normal constituent of
      neuronal cell membranes. The protein misfolding causes rare neurodegenerative
      disorders known as transmissible spongiform encephalopathies or prion diseases.
      These maladies can be sporadic, genetic or infectious. Sporadic prion diseases
      are the most common form mainly affecting aging people. In this work, we
      investigate the biochemical environment in which sporadic prion diseases may
      develop, focusing our attention on the cell membrane of neurons in the aging
      brain. It is well established that with aging the ratio between the most abundant
      lipid components of rafts undergoes a major change: while cholesterol decreases,
      sphingomyelin content rises. Our results indicate that the aging process modifies
      the compartmentalization of PrP(C). In old mice, this change favors PrP(C)
      accumulation in detergent-resistant membranes, particularly in hippocampi. To
      confirm the relationship between lipid content changes and PrP(C) translocation
      into detergent-resistant membranes (DRMs), we looked at PrP(C)
      compartmentalization in hippocampi from acid sphingomyelinase (ASM) knockout (KO)
      mice and synaptosomes enriched in sphingomyelin. In the presence of high
      sphingomyelin content, we observed a significant increase of PrP(C) in DRMS. This
      process is not due to higher levels of total protein and it could, in turn, favor
      the onset of sporadic prion diseases during aging as it increases the PrP
      intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin
      in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease
      resistant PrP formation. This may suggest an involvement of PrP lipid environment
      in prion formation and consequently it may play a role in the onset or
      development of sporadic forms of prion diseases. 

PMID- 24040216
TI  - Perceived discrimination and self-rated health in Europe: evidence from the
      European Social Survey (2010).
AB  - INTRODUCTION: Studies have shown that perceived discrimination has an impact on
      our physical and mental health. A relevant part of literature has highlighted the
      influence of discrimination based on race or ethnicity on mental and physical
      health outcomes. However, the influence of other types of discrimination on
      health has been understudied. This study is aimed to explore how different types
      of discrimination are related to our subjective state of health, and so to
      compare the intensity of these relationships in the European context. METHODS: We
      have performed a multilevel ordered analysis on the fifth wave of the European
      Social Survey (ESS 2010). This dataset has 52,458 units at individual level that
      are grouped in 26 European countries. In this study, the dependent variable is
      self-rated health (SRH) that is analyzed in relationship to ten explanatory
      variables of perceived discrimination: color or race, nationality, religion,
      language, ethnic group, age, gender, sexuality, disability and others. RESULTS:
      The model identifies statistically significant differences in the effect that
      diverse types of perceived discrimination can generate on the self-rated health
      of Europeans. Specifically, this study identifies three well-defined types of
      perceived discrimination that can be related to poor health outcomes: (1) age
      discrimination; (2) disability discrimination; and (3) sexuality discrimination.
      In this sense, the effect on self-rated health of perceived discrimination
      related to aging and disabilities seems to be more relevant than other types of
      discrimination in the European context with a longer tradition in literature
      (e.g. ethnic and/or race-based). CONCLUSION: The present study shows that the
      relationship between perceived discrimination and health inequities in Europe are
      not random, but systematically distributed depending on factors such as age,
      sexuality and disabilities. Therefore the future orientation of EU social
      policies should aim to reduce the impact of these social determinants on health
      equity.

PMID- 24040217
TI  - The design and in vivo evaluation of engineered I-OnuI-based enzymes for HEG gene
      drive.
AB  - The homing endonuclease gene (HEG) drive system, a promising genetic approach for
      controlling arthropod populations, utilises engineered nucleases to spread
      deleterious mutations that inactivate individual genes throughout a target
      population. Previous work with a naturally occurring LAGLIDADG homing
      endonuclease (I-SceI) demonstrated its feasibility in both Drosophila and
      Anopheles. Here we report on the next stage of this strategy: the redesign of
      HEGs with customized specificity in order to drive HEG-induced 'homing' in vivo
      via break-induced homologous recombination. Variants targeting a sequence within
      the Anopheles AGAP004734 gene were created from the recently characterized I-OnuI
      endonuclease, and tested for cleavage activity and frequency of homing using a
      model Drosophila HEG drive system. We observed cleavage and homing at an
      integrated reporter for all endonuclease variants tested, demonstrating for the
      first time that engineered HEGs can cleave their target site in insect germline
      cells, promoting targeted mutagenesis and homing. However, in comparison to our
      previously reported work with I-SceI, the engineered I-OnuI variants mediated
      homing with a reduced frequency, suggesting that site-specific cleavage activity
      is insufficient by itself to ensure efficient homing. Taken together, our
      experiments take a further step towards the development of a viable HEG-based
      population control strategy for insects. 

PMID- 24040218
TI  - ReaDDy--a software for particle-based reaction-diffusion dynamics in crowded
      cellular environments.
AB  - We introduce the software package ReaDDy for simulation of detailed
      spatiotemporal mechanisms of dynamical processes in the cell, based on reaction
      diffusion dynamics with particle resolution. In contrast to other particle-based
      reaction kinetics programs, ReaDDy supports particle interaction potentials. This
      permits effects such as space exclusion, molecular crowding and aggregation to be
      modeled. The biomolecules simulated can be represented as a sphere, or as a more
      complex geometry such as a domain structure or polymer chain. ReaDDy bridges the
      gap between small-scale but highly detailed molecular dynamics or Brownian
      dynamics simulations and large-scale but little-detailed reaction kinetics
      simulations. ReaDDy has a modular design that enables the exchange of the
      computing core by efficient platform-specific implementations or dynamical models
      that are different from Brownian dynamics. 

PMID- 24040219
TI  - Shifts in the microbial community composition of Gulf Coast beaches following
      beach oiling.
AB  - Microorganisms associated with coastal sands serve as a natural biofilter,
      providing essential nutrient recycling in nearshore environments and acting to
      maintain coastal ecosystem health. Anthropogenic stressors often impact these
      ecosystems, but little is known about whether these disturbances can be
      identified through microbial community change. The blowout of the Macondo
      Prospect reservoir on April 20, 2010, which released oil hydrocarbons into the
      Gulf of Mexico, presented an opportunity to examine whether microbial community
      composition might provide a sensitive measure of ecosystem disturbance. Samples
      were collected on four occasions, beginning in mid-June, during initial beach
      oiling, until mid-November from surface sand and surf zone waters at seven
      beaches stretching from Bay St. Louis, MS to St. George Island, FL USA. Oil
      hydrocarbon measurements and NOAA shoreline assessments indicated little to no
      impact on the two most eastern beaches (controls). Sequence comparisons of
      bacterial ribosomal RNA gene hypervariable regions isolated from beach sands
      located to the east and west of Mobile Bay in Alabama demonstrated that regional
      drivers account for markedly different bacterial communities. Individual beaches
      had unique community signatures that persisted over time and exhibited spatial
      relationships, where community similarity decreased as horizontal distance
      between samples increased from one to hundreds of meters. In contrast, sequence
      analyses detected larger temporal and less spatial variation among the water
      samples. Superimposed upon these beach community distance and time relationships,
      was increased variability in bacterial community composition from oil hydrocarbon
      contaminated sands. The increased variability was observed among the core,
      resident, and transient community members, indicating the occurrence of community
      wide impacts rather than solely an overprinting of oil hydrocarbon-degrading
      bacteria onto otherwise relatively stable sand population structures. Among
      sequences classified to genus, Alcanivorax, Alteromonas, Marinobacter,
      Winogradskyella, and Zeaxanthinibacter exhibited the largest relative abundance
      increases in oiled sands. 

PMID- 24040221
TI  - FastDMA: an infinium humanmethylation450 beadchip analyzer.
AB  - DNA methylation is vital for many essential biological processes and human
      diseases. Illumina Infinium HumanMethylation450 Beadchip is a recently developed
      platform studying genome-wide DNA methylation state on more than 480,000 CpG
      sites and a few CHG sites with high data quality. To analyze the data of this
      promising platform, we developed FastDMA which can be used to identify
      significantly differentially methylated probes. Besides single probe analysis,
      FastDMA can also do region-based analysis for identifying the differentially
      methylated region (DMRs). A uniformed statistical model, analysis of covariance
      (ANCOVA), is used to achieve all the analyses in FastDMA. We apply FastDMA on
      three large-scale DNA methylation datasets from The Cancer Genome Atlas (TCGA)
      and find many differentially methylated genomic sites in different types of
      cancer. On the testing datasets, FastDMA shows much higher computational
      efficiency than current tools. FastDMA can benefit the data analyses of large
      scale DNA methylation studies with an integrative pipeline and a high
      computational efficiency. The software is freely available via
      http://bioinfo.au.tsinghua.edu.cn/software/fastdma/. 

PMID- 24040220
TI  - Experimentally validated novel inhibitors of Helicobacter pylori
      phosphopantetheine adenylyltransferase discovered by virtual high-throughput
      screening.
AB  - Helicobacter pylori is a major etiologic agent associated with the development
      and maintenance of human gastritis. The goal of this study was to develop novel
      antibiotics against H. pylori, and we thus targeted H. pylori phosphopantetheine
      adenylyltransferase (HpPPAT). PPAT catalyzes the penultimate step in coenzyme A
      biosynthesis. Its inactivation effectively prevents bacterial viability, making
      it an attractive target for antibacterial drug discovery. We employed virtual
      high-throughput screening and the HpPPAT crystal structure to identify compounds
      in the PubChem database that might act as inhibitors of HpPPAT. d-amethopterin is
      a potential inhibitor for blocking HpPPAT activity and suppressing H. pylori
      viability. Following treatment with d-amethopterin, H. pylori exhibited
      morphological characteristics associated with cell death. d-amethopterin is a
      mixed inhibitor of HpPPAT activity; it simultaneously occupies the HpPPAT 4'
      phosphopantetheine- and ATP-binding sites. Its binding affinity is in the
      micromolar range, implying that it is sufficiently potent to serve as a lead
      compound in subsequent drug development. Characterization of the d-amethopterin
      and HpPPAT interaction network in a docked model will allow us to initiate
      rational drug optimization to improve the inhibitory efficacy of d-amethopterin.
      We anticipate that novel, potent, and selective HpPPAT inhibitors will emerge for
      the treatment of H. pylori infection.

PMID- 24040222
TI  - Association between TYMS expression and efficacy of pemetrexed-based chemotherapy
      in advanced non-small cell lung cancer: a meta-analysis.
AB  - BACKGROUND: The predictive value of thymidylate synthase (TYMS) to sensitivity to
      pemetrexed-based chemotherapy in advanced non-small cell lung cancer (NSCLC)
      patients is controversial. We conducted a meta-analysis of all relevant published
      data to assess the association of TYMS expression with the clinical outcomes of
      pemetrexed-based regimen in advanced NSCLC. PATIENTS AND METHODS: We conducted an
      electronic search using using PubMed, Embase, OVID and Cochrane Library databases
      and manual search. Pooled odds ratio (OR) for the response rate and hazard ratio
      (HR) for the overall survival and progression free survival were calculated using
      the software Revman 5.0. RESULTS: There were 11 studies (n=798) met our criteria
      for evaluation. Response rate to pemetrexed-based regimen was significantly
      higher in patients with low/negative TYMS (OR=2.96, 95%CI [1.81, 4.86] P<0.0001).
      Patients with low/negative TYMS who were treated with pemetrexed-based regimen
      had longer progression free survival (HR 0.50, 95%CI [0.41, 0.61] P <0.00001) and
      overall survival (HR 0.41, 95%CI [0.22, 0.78] P=0.007) than those with
      high/positive TYMS. CONCLUSIONS: Low/negative TYMS expression was significantly
      associated with higher response rate, longer median survival and longer
      progression free survival for advanced NSCLC patients receiving pemtrexed-based
      chemotherapy. Hence, TYMS may be a potential predictor of sensitivity to
      pemtrexed-based chemotherapy in advanced NSCLC. Large scale prospective clinical
      trials are still warranted.

PMID- 24040223
TI  - Expression of heat shock protein (Hsp90) paralogues is regulated by amino acids
      in skeletal muscle of Atlantic salmon.
AB  - Heat shock proteins 90 (Hsp90) have an essential role in sarcomere formation and
      differentiation in skeletal muscle and also act as molecular chaperones during
      protein folding impacting a wide range of physiological processes. We
      characterised and provided a phylogenetically consistent nomenclature for the
      complete repertoire of six Hsp90 paralogues present in duplicated salmonid fish
      genomes (Hsp90alpha1a, Hsp90alpha1b, Hsp90alpha2a, Hsp90alpha2b, Hsp90beta1a and
      Hsp90beta1b). The expression of paralogues in fast skeletal muscle was
      investigated using in vivo fasting-feeding experiments and primary myogenic
      cultures. Fasted juvenile Atlantic salmon (Salmo salar) showed a transient 2 to 8
      fold increase in the expression of all 4 Hsp90alpha paralogues within 24h of
      satiation feeding. Hsp90alpha1a and hsp90alpha1b also showed a pronounced
      secondary increase in expression after 10 days, concomitant with muscle
      differentiation and the expression of myogenin and sarcomeric proteins (mlc2,
      myhc). Hsp90beta1b was constitutively expressed whereas Hsp90beta1a expression
      was downregulated 10-fold between fasted and fed individuals. Hsp90alpha1a and
      Hsp90alpha1b were upregulated 10 to 15-fold concomitant with myotube formation
      and muscle differentiation in vitro whereas other Hsp90 paralogues showed no
      change in expression. In cells starved of amino acid (AA) and serum for 72h the
      addition of AA, but not insulin-like growth factor 1, increased phosphorylation
      of mTor and expression of all 4 hsp90alpha paralogues and associated co
      chaperones including hsp30, tbcb, pdia4, pdia6, stga and fk504bp1, indicating a
      general activation of the protein folding response. In contrast, Hsp90beta1a
      expression in vitro was unresponsive to AA treatment indicating that some other
      as yet uncharacterised signal(s) regulate its expression in response to altered
      nutritional state. 

PMID- 24040224
TI  - Birth by caesarean section and prevalence of risk factors for non-communicable
      diseases in young adults: a birth cohort study.
AB  - BACKGROUND: Conflicting findings on the risk of obesity among subjects born by
      caesarean section have been published. Caesarean section should also increase the
      risk of obesity related cardiovascular risk factors if type of delivery is
      associated with obesity later in life. This study was aimed at assessing the
      effect of type of delivery on metabolic cardiovascular risk factors in early
      adulthood. METHODOLOGY AND PRINCIPAL FINDINGS: In 1982, maternity hospitals in
      Pelotas, southern Brazil, were visited and those livebirths whose family lived in
      the urban area of the city have been followed. In 2000, when male subjects
      undertook the Army entrance examination (n=2200), fat mass and fat free mass were
      estimated through bioimpedance. In 2004-2005, we attempted to follow the whole
      cohort (n=4297), and the following outcomes were studied: blood pressure; HDL
      cholesterol; triglycerides; random blood glucose, C-reactive protein, waist
      circumference and body mass index. The estimates were adjusted for the following
      confounders: family income at birth; maternal schooling; household assets index
      in childhood; maternal skin color; birth order; maternal age; maternal
      prepregnancy weight; maternal height; maternal smoking during pregnancy;
      birthweight and family income at early adulthood. RESULTS: In the crude analyses,
      blood pressure (systolic, diastolic and mean arterial pressure) and body mass
      index were higher among subjects who were delivered through caesarean section.
      After controlling for confounders, systolic blood pressure was 1.15 mmHg (95%
      confidence interval: 0.05; 2.25) higher among subjects delivered by caesarean
      section, and BMI 0.40 kg/m(2) (95% confidence interval: 0.08; 0.71). After
      controlling for BMI the effect on systolic blood pressure dropped to 0.60 mmHg
      (95% confidence interval: -0.47; 1.67). Fat mass at 18 years of age was also
      higher among subjects born by caesarean section. CONCLUSION: Caesarean section
      was associated with a small increased in systolic blood pressure, body mass index
      and fat mass.

PMID- 24040225
TI  - Global patterns of diversity and selection in human tyrosinase gene.
AB  - Global variation in skin pigmentation is one of the most striking examples of
      environmental adaptation in humans. More than two hundred loci have been
      identified as candidate genes in model organisms and a few tens of these have
      been found to be significantly associated with human skin pigmentation in genome
      wide association studies. However, the evolutionary history of different
      pigmentation genes is rather complex: some loci have been subjected to strong
      positive selection, while others evolved under the relaxation of functional
      constraints in low UV environment. Here we report the results of a global study
      of the human tyrosinase gene, which is one of the key enzymes in melanin
      production, to assess the role of its variation in the evolution of skin
      pigmentation differences among human populations. We observe a higher rate of non
      synonymous polymorphisms in the European sample consistent with the relaxation of
      selective constraints. A similar pattern was previously observed in the MC1R gene
      and concurs with UV radiation-driven model of skin color evolution by which
      mutations leading to lower melanin levels and decreased photoprotection are
      subject to purifying selection at low latitudes while being tolerated or even
      favored at higher latitudes because they facilitate UV-dependent vitamin D
      production. Our coalescent date estimates suggest that the non-synonymous
      variants, which are frequent in Europe and North Africa, are recent and have
      emerged after the separation of East and West Eurasian populations. 

PMID- 24040227
TI  - Phage display-derived binders able to distinguish Listeria monocytogenes from
      other Listeria species.
AB  - The objective of this study was to produce phage display-derived binders with the
      ability to distinguish Listeria monocytogenes from other Listeria spp., which may
      have potential utility to enhance detection of Listeria monocytogenes. To obtain
      binders with the desired binding specificity a series of surface and solution
      phage-display biopannings were performed. Initially, three rounds of surface
      biopanning against gamma-irradiated L. monocytogenes serovar 4b cells were
      performed followed by an additional surface biopanning round against L.
      monocytogenes 4b which included prior subtraction biopanning against gamma
      irradiated L. innocua cells. In an attempt to further enhance binder specificity
      for L. monocytogenes 4b two rounds of solution biopanning were performed, both
      rounds included initial subtraction solution biopanning against L. innocua.
      Subsequent evaluations were performed on the phage clones by phage binding ELISA.
      All phage clones tested from the second round of solution biopanning had higher
      specificity for L. monocytogenes 4b than for L. innocua and three other foodborne
      pathogens (Salmonella spp., Escherichia coli and Campylobacter jejuni). Further
      evaluation with five other Listeria spp. revealed that one phage clone in
      particular, expressing peptide GRIADLPPLKPN, was highly specific for L.
      monocytogenes with at least 43-fold more binding capability to L. monocytogenes
      4b than to any other Listeria sp. This proof-of-principle study demonstrates how
      a combination of surface, solution and subtractive biopanning was used to
      maximise binder specificity. L. monocytogenes-specific binders were obtained
      which could have potential application in novel detection tests for L.
      monocytogenes, benefiting both the food and medical industries. 

PMID- 24040226
TI  - A novel bidirectional interaction between endothelin-3 and retinoic acid in rat
      enteric nervous system precursors.
AB  - BACKGROUND: Signaling through the endothelin receptor B (EDNRB) is critical for
      the development of the enteric nervous system (ENS) and mutations in endothelin
      system genes cause Hirschsprung's aganglionosis in humans. Penetrance of the
      disease is modulated by other genetic factors. Mutations affecting retinoic acid
      (RA) signaling also produce aganglionosis in mice. Thus, we hypothesized that RA
      and endothelin signaling pathways may interact in controlling development of the
      ENS. METHODS: Rat immunoselected ENS precursor cells were cultured with the EDNRB
      ligand endothelin-3, an EDNRB-selective antagonist (BQ-788), and/or RA for 3 or
      14 days. mRNA levels of genes related to ENS development, RA- and EDNRB-signaling
      were measured at 3 days. Proliferating cells and cells expressing neuronal,
      glial, and myofibroblast markers were quantified. RESULTS: Culture of isolated
      ENS precursors for 3 days with RA decreases expression of the endothelin-3 gene
      and that of its activation enzyme. These changes are associated with glial
      proliferation, a higher percentage of glia, and a lower percentage of neurons
      compared to cultures without RA. These changes are independent of EDNRB
      signaling. Conversely, EDNRB activation in these cultures decreases expression of
      RA receptors beta and gamma mRNA and affects the expression of the RA synthetic
      and degradative enzymes. These gene expression changes are associated with
      reduced glial proliferation and a lower percentage of glia in the culture. Over
      14 days in the absence of EDNRB signaling, RA induces the formation of a
      heterocellular plexus replete with ganglia, glia and myofibroblasts. CONCLUSIONS:
      A complex endothelin-RA interaction exists that coordinately regulates the
      development of rat ENS precursors in vitro. These results suggest that
      environmental RA may modulate the expression of aganglionosis in individuals with
      endothelin mutations.

PMID- 24040228
TI  - Evaluating social and ecological vulnerability of coral reef fisheries to climate
      change.
AB  - There is an increasing need to evaluate the links between the social and
      ecological dimensions of human vulnerability to climate change. We use an
      empirical case study of 12 coastal communities and associated coral reefs in
      Kenya to assess and compare five key ecological and social components of the
      vulnerability of coastal social-ecological systems to temperature induced coral
      mortality [specifically: 1) environmental exposure; 2) ecological sensitivity; 3)
      ecological recovery potential; 4) social sensitivity; and 5) social adaptive
      capacity]. We examined whether ecological components of vulnerability varied
      between government operated no-take marine reserves, community-based reserves,
      and openly fished areas. Overall, fished sites were marginally more vulnerable
      than community-based and government marine reserves. Social sensitivity was
      indicated by the occupational composition of each community, including the
      importance of fishing relative to other occupations, as well as the
      susceptibility of different fishing gears to the effects of coral bleaching on
      target fish species. Key components of social adaptive capacity varied
      considerably between the communities. Together, these results show that different
      communities have relative strengths and weaknesses in terms of social-ecological
      vulnerability to climate change. 

PMID- 24040229
TI  - Risk factors associated with the community-acquired colonization of extended
      spectrum beta-lactamase (ESBL) positive Escherichia Coli. an exploratory case
      control study.
AB  - BACKGROUND: The number of extended-spectrum beta-lactamase (ESBL) positive (+)
      Escherichia coli is increasing worldwide. In contrast with many other multidrug
      resistant bacteria, it is suspected that they predominantly spread within the
      community. The objective of this study was to assess factors associated with
      community-acquired colonization of ESBL (+) E. coli. METHODS: We performed a
      matched case-control study at the Charite University Hospital Berlin between May
      2011 and January 2012. Cases were defined as patients colonized with community
      acquired ESBL (+) E. coli identified <72 h after hospital admission. Controls
      were patients that carried no ESBL-positive bacteria but an ESBL-negative E.coli
      identified <72 h after hospital admission. Two controls per case were chosen from
      potential controls according to admission date. Case and control patients
      completed a questionnaire assessing nutritional habits, travel habits, household
      situation and language most commonly spoken at home (mother tongue). An
      additional rectal swab was obtained together with the questionnaire to verify
      colonization status. Genotypes of ESBL (+) E. coli strains were determined by PCR
      and sequencing. Risk factors associated with ESBL (+) E. coli colonization were
      analyzed by a multivariable conditional logistic regression analysis. RESULTS: We
      analyzed 85 cases and 170 controls, respectively. In the multivariable analysis,
      speaking an Asian language most commonly at home (OR = 13.4, CI 95% 3.3-53.8;
      p<0.001) and frequently eating pork (>= 3 meals per week) showed to be
      independently associated with ESBL colonization (OR = 3.5, CI 95% 1.8-6.6;
      p<0.001). The most common ESBL genotypes were CTX-M-1 with 44% (n = 37), CTX-M-15
      with 28% (n = 24) and CTX-M-14 with 13% (n = 11). CONCLUSION: An Asian mother
      tongue and frequently consuming certain types of meat like pork can be
      independently associated with the colonization of ESBL-positive bacteria. We
      found neither frequent consumption of poultry nor previous use of antibiotics to
      be associated with ESBL colonization.

PMID- 24040230
TI  - A model for cell population size control using asymmetric division.
AB  - In multicellular organisms one can find examples where a growing tissue divides
      up until some final fixed cell number. Asymmetric division plays a prevalent
      feature in tissue differentiation in these organisms, where the daughters of each
      asymmetric division inherit unequal amounts of a fate determining molecule and as
      a result follow different developmental fates. In some tissues the accumulation
      or decrease of cell cycle regulators acts as an intrinsic timing mechanism
      governing proliferation. Here we present a minimal model based on asymmetric
      division and dilution of a cell-cycle regulator that can generate any final
      population size that might be needed. We show that within the model there are a
      variety of growth mechanisms from linear to non-linear that can lead to the same
      final cell count. Interestingly, when we include noise at division we find that
      there are special final cell population sizes that can be generated with high
      confidence that are flanked by population sizes that are less robust to division
      noise. When we include further perturbations in the division process we find that
      these special populations can remain relatively stable and in some cases even
      improve in their fidelity. 

PMID- 24040231
TI  - Foot disorders, foot posture, and foot function: the Framingham foot study.
AB  - INTRODUCTION: Foot disorders are common among older adults and may lead to
      outcomes such as falls and functional limitation. However, the associations of
      foot posture and foot function to specific foot disorders at the population level
      remain poorly understood. The purpose of this study was to assess the relation
      between specific foot disorders, foot posture, and foot function. METHODS:
      Participants were from the population-based Framingham Foot Study. Quintiles of
      the modified arch index and center of pressure excursion index from plantar
      pressure scans were used to create foot posture and function subgroups. Adjusted
      odds ratios of having each specific disorder were calculated for foot posture and
      function subgroups relative to a referent 3 quintiles. RESULTS: Pes planus foot
      posture was associated with increased odds of hammer toes and overlapping toes.
      Cavus foot posture was not associated with the foot disorders evaluated. Odds of
      having hallux valgus and overlapping toes were significantly increased in those
      with pronated foot function, while odds of hallux valgus and hallux rigidus were
      significantly decreased in those with supinated function. CONCLUSIONS: Foot
      posture and foot function were associated with the presence of specific foot
      disorders.

PMID- 24040232
TI  - Dogs and humans share a common susceptibility gene SRBD1 for glaucoma risk.
AB  - Glaucoma is a degenerative optic neuropathy that is associated with elevated
      intraocular pressure. Primary open angle glaucoma is the most common type of
      glaucoma in canines, and its highest incidence among dog breeds has been reported
      in Shiba-Inus, followed by Shih-Tzus. These breeds are known to have an abnormal
      iridocorneal angle and dysplastic prectinate ligament. However, the hereditary
      and genetic backgrounds of these dogs have not yet been clarified. In this study,
      we investigated the association between polymorphisms of the glaucoma candidate
      genes, SRBD1, ELOVL5, and ADAMTS10, and glaucoma in Shiba-Inus and Shih-Tzus. We
      analyzed 11 polymorphisms in these three genes using direct DNA sequencing. Three
      SRBD1 SNPs, rs8655283, rs22018514 and rs22018513 were significantly associated
      with glaucoma in Shiba-Inus, while rs22018513, a synonymous SNP in exon 4, showed
      the strongest association (P = 0.00039, OR = 3.03). Conditional analysis revealed
      that rs22018513 could account for most of the association of these SNPs with
      glaucoma in Shiba-Inus. In Shih-Tzus, only rs9172407 in the SRBD1 intron 1 was
      significantly associated with glaucoma (P = 0.0014, OR = 5.25). There were no
      significant associations between the ELOVL5 or ADAMTS10 polymorphisms and
      glaucoma in Shiba-Inus and Shih-Tzus. The results showed that SRBD1 polymorphisms
      play an important role in glaucoma pathology in both Shiba-Inus and Shih-Tzus.
      SRBD1 polymorphisms have also been associated with normal- and high-tension
      glaucomas in humans. Therefore, SRBD1 may be a common susceptibility gene for
      glaucoma in humans and dogs. We anticipate that the nucleotide sequencing data
      from this study can be used in genetic testing to determine for the first time,
      the genetic status and susceptibility of glaucoma in dogs, with high precision.
      Moreover, canine glaucoma resulting from SRBD1 polymorphisms could be a useful
      animal model to study human glaucoma.

PMID- 24040233
TI  - Did terrestrial diversification of amoebas (amoebozoa) occur in synchrony with
      land plants?
AB  - Evolution of lineage diversification through time is an active area of research
      where much progress has been made in the last decade. Contrary to the situation
      in animals and plants little is known about how diversification rates have
      evolved in most major groups of protist. This is mainly due to uncertainty about
      phylogenetic relationships, scarcity of the protist fossil record and the unknown
      diversity within these lineages. We have analyzed the evolutionary history of the
      supergroup Amoebozoa over the last 1000 million years using molecular dating and
      species number estimates. After an origin in the marine environment we have dated
      the colonization of terrestrial habitats by three distinct lineages of Amoebozoa:
      Dictyostelia, Myxogastria and Arcellinida. The common ancestor of the two sister
      taxa, Dictyostelia and Myxogastria, appears to have existed before the
      colonization of land by plants. In contrast Arcellinida seems to have diversify
      in synchrony with land plant radiation, and more specifically with that of
      mosses. Detection of acceleration of diversification rates in Myxogastria and
      Arcellinida points to a co-evolution within the terrestrial habitats, where land
      plants and the amoebozoans may have interacted during the evolution of these new
      ecosystems. 

PMID- 24040234
TI  - Lack of association of variants previously associated with anti-TNF medication
      response in rheumatoid arthritis patients: results from a homogeneous Greek
      population.
AB  - Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very
      successful in patients with rheumatoid arthritis (RA), showing beneficial effects
      in approximately 50-60% of the patients. However, a significant subset of
      patients does not respond to anti-TNF agents, for reasons that are still unknown.
      The aim of this study was to validate five single nucleotide polymorphisms (SNPs)
      of PTPRC, CD226, AFF3, MyD88 and CHUK gene loci that have previously been
      reported to predict anti-TNF outcome. In addition, two markers of RA
      susceptibility, namely TRAF1/C5 and STAT4 were assessed, in a cohort of anti-TNF
      treated RA patients, from the homogeneous Greek island of Crete, Greece. The RA
      patient cohort consisted of 183 patients treated with either of 3 anti-TNF
      biologic agents (infliximab, adalimumab and etanercept) from the Clinic of
      Rheumatology of the University Hospital of Crete. The SNPs were genotyped by
      TaqMan assays or following the Restriction Fragments Length Polymorphisms (RFLPs)
      approach. Disease activity score in 28 joints (DAS28) at baseline and after 6
      months were available for all patients and analysis of good versus poor response
      at 6 months was performed for each SNP. None of the 7 genetic markers correlated
      with treatment response. We conclude that the gene polymorphisms under
      investigation are not strongly predictive of anti-TNF response in RA patients
      from Greece. 

PMID- 24040235
TI  - Rapid antemortem detection of CWD prions in deer saliva.
AB  - Chronic wasting disease (CWD) is an efficiently transmitted prion disease of
      cervids, now identified in 22 United States, 2 Canadian provinces and Korea. One
      hallmark of CWD is the shedding of infectious prions in saliva, as demonstrated
      by bioassay in deer. It is also clear that the concentration of prions in saliva,
      blood, urine and feces is much lower than in the nervous system or lymphoid
      tissues. Rapid in vitro detection of CWD (and other) prions in body fluids and
      excreta has been problematic due to the sensitivity limits of direct assays
      (western blotting, ELISA) and the presence of inhibitors in these complex
      biological materials that hamper detection. Here we use real-time quaking induced
      conversion (RT-QuIC) to demonstrate CWD prions in both diluted and prion-enriched
      saliva samples from asymptomatic and symptomatic white-tailed deer. CWD prions
      were detected in 14 of 24 (58.3%) diluted saliva samples from CWD-exposed white
      tailed deer, including 9 of 14 asymptomatic animals (64.2%). In addition, a
      phosphotungstic acid enrichment enhanced the RT-QuIC assay sensitivity, enabling
      detection in 19 of 24 (79.1%) of the above saliva samples. Bioassay in Tg[CerPrP]
      mice confirmed the presence of infectious prions in 2 of 2 RT-QuIC-positive
      saliva samples so examined. The modified RT-QuIC analysis described represents a
      non-invasive, rapid ante-mortem detection of prions in complex biologic fluids,
      excreta, or environmental samples as well as a tool for exploring prion
      trafficking, peripheralization, and dissemination. 

PMID- 24040236
TI  - The burden of bacterial vaginosis: women's experience of the physical, emotional,
      sexual and social impact of living with recurrent bacterial vaginosis.
AB  - BACKGROUND: Bacterial vaginosis is a common vaginal infection, causing an
      abnormal vaginal discharge and/or odour in up to 50% of sufferers. Recurrence is
      common following recommended treatment. There are limited data on women's
      experience of bacterial vaginosis, and the impact on their self-esteem, sexual
      relationships and quality of life. The aim of this study was to explore the
      experiences and impact of recurrent bacterial vaginosis on women. METHODS: A
      social constructionist approach was chosen as the framework for the study. Thirty
      five women with male and/or female partners participated in semi-structured
      interviews face-to-face or by telephone about their experience of recurrent
      bacterial vaginosis. RESULTS: Recurrent bacterial vaginosis impacted on women to
      varying degrees, with some women reporting it had little impact on their lives
      but most reporting it had a moderate to severe impact. The degree to which it
      impacted on women physically, emotionally, sexually and socially often depended
      on the frequency of episodes and severity of symptoms. Women commonly reported
      that symptoms of bacterial vaginosis made them feel embarrassed, ashamed, 'dirty'
      and very concerned others may detect their malodour and abnormal discharge. The
      biggest impact of recurrent bacterial vaginosis was on women's self-esteem and
      sex lives, with women regularly avoiding sexual activity, in particular oral sex,
      as they were too embarrassed and self-conscious of their symptoms to engage in
      these activities. Women often felt confused about why they were experiencing
      recurrent bacterial vaginosis and frustrated at their lack of control over
      recurrence. CONCLUSION: Women's experience of recurrent bacterial vaginosis
      varied broadly and significantly in this study. Some women reported little impact
      on their lives but most reported a moderate to severe impact, mainly on their
      self-esteem and sex life. Further support and acknowledgement of these impacts
      are required when managing women with recurrent bacterial vaginosis.

PMID- 24040237
TI  - How do amoebae swim and crawl?
AB  - The surface behaviour of swimming amoebae was followed in cells bearing a cAR1
      paGFP (cyclic AMP receptor fused to a photoactivatable-GFP) construct. Sensitized
      amoebae were placed in a buoyant medium where they could swim toward a
      chemoattractant cAMP source. paGFP, activated at the cell's front, remained
      fairly stationary in the cell's frame as the cell advanced; the label was not
      swept rearwards. Similar experiments with chemotaxing cells attached to a
      substratum gave the same result. Furthermore, if the region around a lateral
      projection near a crawling cell's front is marked, the projection and the
      labelled cAR1 behave differently. The label spreads by diffusion but otherwise
      remains stationary in the cell's frame; the lateral projection moves rearwards on
      the cell (remaining stationary with respect to the substrate), so that it ends up
      outside the labelled region. Furthermore, as cAR1-GFP cells move, they
      occasionally do so in a remarkably straight line; this suggests they do not need
      to snake to move on a substratum. Previously, we suggested that the surface
      membrane of a moving amoeba flows from front to rear as part of a polarised
      membrane trafficking cycle. This could explain how swimming amoebae are able to
      exert a force against the medium. Our present results indicate that, in amoebae,
      the suggested surface flow does not exist: this implies that they swim by shape
      changes. 

PMID- 24040238
TI  - Detection of soluble ST2 in human follicular fluid and luteinized granulosa
      cells.
AB  - Follicular fluid (FF) contains various cytokines that are involved with
      folliculogenesis, some of which have been shown to be associated with oocyte
      quality and the implantation potential of a resulting embryo. Several IL-1 family
      members have previously been identified in FF. This study investigates a newly
      identified member of the family, IL-33, and its receptor ST2, comparing values to
      those of FF Granulocyte-Colony Stimulating Factor (G-CSF)--a known predictor of
      Assisted Reproductive Technology (ART) success. FF was collected from patients
      undergoing in vitro fertilisation/intra-cytoplasmic sperm injection (IVF/ICSI) at
      oocyte retrieval to analyse IL-33 and sST2 expression in human follicles. sST2,
      but not IL-33, is highly increased in the FF compared to plasma levels (up to 7.9
      fold), with higher levels in larger follicles (p<0.05). Furthermore, we identify
      that human luteinised granulosa cells are one possible source of the FF sST2, as
      these cells express and secrete sST2 when cultured ex vivo. FF associated with
      oocytes which when fertilised develop into good quality embryos have higher sST2
      levels than those which are graded average (p<0.01). These embryos were
      transferred to the patient and levels of FF sST2 compared between successful and
      unsuccessful ICSI cycles. However unlike G-CSF, sST2 levels cannot be used to
      predict cycle outcome.

PMID- 24040239
TI  - A new cryptic species of South American freshwater pufferfish of the genus
      Colomesus (Tetraodontidae), based on both morphology and DNA data.
AB  - The Tetraodontidae are an Acantomorpha fish family with circumglobal distribution
      composed of 189 species grouped in 19 genera, occurring in seas, estuaries, and
      rivers between the tropical and temperate regions. Of these, the genus Colomesus
      is confined to South America, with what have been up to now considered only two
      species. C. asellus is spread over the entire Amazon, Tocantins-Araguaia
      drainages, and coastal environments from the Amazon mouth to Venezuela, and is
      the only freshwater puffers on that continent. C. psittacus is found in coastal
      marine and brackish water environments from Cuba to the northern coast of South
      America as far south as to Sergipe in Brazil. In the present contribution we used
      morphological data along with molecular systematics techniques to investigate the
      phylogeny and phylogeography of the freshwater pufferfishes of the genus
      Colomesus. The molecular part is based on a cytochrome C oxidase subunit I
      dataset constructed from both previously published and newly determined
      sequences, obtained from specimens collected from three distinct localities in
      South America. Our results from both molecular and morphological approaches
      enable us to identify and describe a new Colomesus species from the Tocantins
      River. We also discuss aspects of the historical biogeography and phylogeography
      of the South American freshwater pufferfishes, suggesting that it could be more
      recent than previously expected. 

PMID- 24040240
TI  - A user-friendly model for spray drying to aid pharmaceutical product development.
AB  - The aim of this study was to develop a user-friendly model for spray drying that
      can aid in the development of a pharmaceutical product, by shifting from a trial
      and-error towards a quality-by-design approach. To achieve this, a spray dryer
      model was developed in commercial and open source spreadsheet software. The
      output of the model was first fitted to the experimental output of a Buchi B-290
      spray dryer and subsequently validated. The predicted outlet temperatures of the
      spray dryer model matched the experimental values very well over the entire range
      of spray dryer settings that were tested. Finally, the model was applied to
      produce glassy sugars by spray drying, an often used excipient in formulations of
      biopharmaceuticals. For the production of glassy sugars, the model was extended
      to predict the relative humidity at the outlet, which is not measured in the
      spray dryer by default. This extended model was then successfully used to predict
      whether specific settings were suitable for producing glassy trehalose and inulin
      by spray drying. In conclusion, a spray dryer model was developed that is able to
      predict the output parameters of the spray drying process. The model can aid the
      development of spray dried pharmaceutical products by shifting from a trial-and
      error towards a quality-by-design approach. 

PMID- 24040241
TI  - Multicompartmental pharmacokinetic model of tenofovir delivery by a vaginal gel.
AB  - BACKGROUND: Trials of a vaginal Tenofovir gel for pre-exposure prophylaxis (PrEP)
      for HIV have given conflicting results. Knowledge of concentrations of Tenofovir
      and its active form Tenofovir diphosphate, at putative sites of anti-HIV
      functioning, is central to understanding trial outcomes and design of products
      and dosage regimens. Topical Tenofovir delivery to the vaginal environment is
      complex, multivariate and non-linear; determinants relate to drug, vehicle,
      dosage regimen, and environment. Experimental PK methods cannot yield mechanistic
      understanding of this process, and have uncontrolled variability in drug
      sampling. Mechanistic modeling of the process could help delineate its
      determinants, and be a tool in design and interpretation of products and trials.
      METHODS AND FINDINGS: We created a four-compartment mass transport model for
      Tenofovir delivery by a gel: gel, epithelium, stroma, blood. Transport was
      diffusion-driven in vaginal compartments; blood concentration was time-varying
      but homogeneous. Parameters for the model derived from in vitro and in vivo PK
      data, to which model predictions gave good agreement. Steep concentration
      gradients occurred in stroma <= 8 hours after gel release. Increasing epithelial
      thickness delayed initial TFV delivery to stroma and its decline: tmax increased
      but AUC at 24 hours was not significantly altered. At 24 and 48 hours, stromal
      concentrations were 6.3% and 0.2% of C(max). Concentrations in simulated biopsies
      overestimated stromal concentrations, as much as ~5X, depending upon time of
      sampling, biopsy thickness and epithelial thickness. CONCLUSIONS: There was
      reasonably good agreement of model predictions with clinical PK data. Conversion
      of TFV to TFV-DP was not included, but PK data suggest a linear relationship
      between them. Thus contrasts predicted by this model can inform design of gels
      and dosage regimens in clinical trials, and interpretation of PK data. This mass
      transport based approach can be extended to TFV conversion to TFV-DP, and to
      other drugs and dosage forms.

PMID- 24040242
TI  - Single cell synchrotron FT-IR microspectroscopy reveals a link between neutral
      lipid and storage carbohydrate fluxes in S. cerevisiae.
AB  - In most organisms, storage lipids are packaged into specialized structures called
      lipid droplets. These contain a core of neutral lipids surrounded by a monolayer
      of phospholipids, and various proteins which vary depending on the species.
      Hydrophobic structural proteins stabilize the interface between the lipid core
      and aqueous cellular environment (perilipin family of proteins, apolipoproteins,
      oleosins). We developed a genetic approach using heterologous expression in
      Saccharomyces cerevisiae of the Arabidopsis thaliana lipid droplet oleosin and
      caleosin proteins AtOle1 and AtClo1. These transformed yeasts overaccumulate
      lipid droplets, leading to a specific increase in storage lipids. The phenotype
      of these cells was explored using synchrotron FT-IR microspectroscopy to
      investigate the dynamics of lipid storage and cellular carbon fluxes reflected as
      changes in spectral fingerprints. Multivariate statistical analysis of the data
      showed a clear effect on storage carbohydrates and more specifically, a decrease
      in glycogen in our modified strains. These observations were confirmed by
      biochemical quantification of the storage carbohydrates glycogen and trehalose.
      Our results demonstrate that neutral lipid and storage carbohydrate fluxes are
      tightly connected and co-regulated. 

PMID- 24040243
TI  - Lungworm Infections in German dairy cattle herds--seroprevalence and GIS
      supported risk factor analysis.
AB  - In November 2008, a total of 19,910 bulk tank milk (BTM) samples were obtained
      from dairy farms from all over Germany, corresponding to about 20% of all German
      dairy herds, and analysed for antibodies against the bovine lungworm Dictyocaulus
      viviparus by use of the recombinant MSP-ELISA. A total number of 3,397 (17.1%; n
      = 19,910) BTM samples tested seropositive. The prevalences in individual German
      federal states varied between 0.0% and 31.2% positive herds. A geospatial map was
      drawn to show the distribution of seropositive and seronegative herds per postal
      code area. ELISA results were further analysed for associations with land-use and
      climate data. Bivariate statistical analysis was used to identify potential
      spatial risk factors for dictyocaulosis. Statistically significant positive
      associations were found between lungworm seropositive herds and the proportion of
      water bodies and grassed area per postal code area. Variables that showed a
      statistically significant association with a positive BTM test were included in a
      logistic regression model, which was further refined by controlled stepwise
      selection of variables. The low Pseudo R(2) values (0.08 for the full model and
      0.06 for the final model) and further evaluation of the model by ROC analysis
      indicate that additional, unrecorded factors (e.g. management factors) or random
      effects may substantially contribute to lungworm infections in dairy cows.
      Veterinarians should include lungworms in the differential diagnosis of
      respiratory disease in dairy cattle, particularly those at pasture. Monitoring of
      herds through BTM screening for antibodies can help farmers and veterinarians
      plan and implement appropriate control measures.

PMID- 24040244
TI  - CCR7 expression and intratumoral FOXP3+ regulatory T cells are correlated with
      overall survival and lymph node metastasis in gastric cancer.
AB  - The aim of this study was to investigate the prognostic value of chemokine
      receptor CCR7 expression and intratumoral FOXP3(+) regulatory T cells (Tregs) in
      gastric cancer. CCR7(+) tumor cells and FOXP3(+) Tregs were assessed by
      immunohistochemistry in tissue microarrays containing gastric cancer from 133
      patients. Prognostic effects of low or high CCR7 and FOXP3 expression were
      evaluated by Cox regression and Kaplan-Meier analysis, as well as the correlation
      between CCR7 positive score and intratumoral FOXP3(+) cell number in a
      longitudinal assessment. The analysis showed that the high expression levels of
      CCR7 and FOXP3 were detected in 69.9% and 65.4% of cases, respectively. High CCR7
      expression in gastric cancer cells was significantly associated with poor overall
      survival (OS) (P = 0.010) and lymph node metastasis (P = 0.009), and was an
      independent factor for worse OS (P = 0.023) by multivariate analysis. High
      numbers of intratumoral FOXP3(+) Tregs significantly correlated with shorter OS
      (P = 0.021) and lymph node metastasis (P = 0.024), and was also an independent
      factor for adverse OS (P = 0.035). Furthermore, there was a significantly
      positive correlation between CCR7 positive score and intratumoral FOXP3(+) cell
      number (r = 0.949, P<0.001). These results revealed that CCR7 expression in
      gastric cancer cells and intratumoral FOXP3(+) Tregs could be considered as a co
      indicator of clinical prognosis of gastric cancer.

PMID- 24040245
TI  - Harming ourselves and defiling others: what determines a moral domain?
AB  - Recent work has distinguished "harm" from "purity" violations, but how does an
      act get classified as belonging to a domain in the first place? We demonstrate
      the impact of not only the kind of action (e.g., harmful versus impure) but also
      its target (e.g., oneself versus another). Across two experiments, common
      signatures of harm and purity tracked with other-directed and self-directed
      actions, respectively. First, participants judged self-directed acts as primarily
      impure and other-directed acts as primarily harmful. Second, conservatism
      predicted harsher judgments of self-directed but not other-directed acts. Third,
      while participants delivered harsher judgments of intentional versus accidental
      acts, this effect was smaller for self-directed than other-directed acts.
      Finally, participants judged self-directed acts more harshly when focusing on the
      actor's character versus the action itself; other-directed acts elicited the
      opposite pattern. These findings suggest that moral domains are defined not only
      by the kind of action but also by the target of the action. 

PMID- 24040246
TI  - Alterations in energy metabolism, neuroprotection and visual signal transduction
      in the retina of Parkinsonian, MPTP-treated monkeys.
AB  - Parkinson disease is mainly characterized by the degeneration of dopaminergic
      neurons in the central nervous system, including the retina. Different
      interrelated molecular mechanisms underlying Parkinson disease-associated
      neuronal death have been put forward in the brain, including oxidative stress and
      mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) to monkeys elicits the appearance of a
      parkinsonian syndrome, including morphological and functional impairments in the
      retina. However, the intracellular events leading to derangement of dopaminergic
      and other retinal neurons in MPTP-treated animal models have not been so far
      investigated. Here we have used a comparative proteomics approach to identify
      proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins
      were solubilized from the neural retinas of control and MPTP-treated animals,
      labelled separately with two different cyanine fluorophores and run pairwise on
      2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to
      exhibit statistically significant differences in their expression levels, of at
      least +/- 1.4-fold, in the parkinsonian monkey retina compared with controls.
      Most of these spots were excised from preparative 2D gels, trypsinized and
      subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for
      protein sequence database interrogation, and 15 different proteins were
      successfully identified, of which 13 were underexpressed and 2 overexpressed.
      These proteins were involved in key cellular functional pathways such as
      glycolysis and mitochondrial electron transport, neuronal protection against
      stress and survival, and phototransduction processes. These functional categories
      underscore that alterations in energy metabolism, neuroprotective mechanisms and
      signal transduction are involved in MPTP-induced neuronal degeneration in the
      retina, in similarity to mechanisms thought to underlie neuronal death in the
      Parkinson's diseased brain and neurodegenerative diseases of the retina proper.

PMID- 24040247
TI  - Transcriptome analysis of yellow horn (Xanthoceras sorbifolia Bunge): a potential
      oil-rich seed tree for biodiesel in China.
AB  - BACKGROUND: Yellow horn (Xanthoceras sorbifolia Bunge) is an oil-rich seed shrub
      that grows well in cold, barren environments and has great potential for
      biodiesel production in China. However, the limited genetic data means that
      little information about the key genes involved in oil biosynthesis is available,
      which limits further improvement of this species. In this study, we describe
      sequencing and de novo transcriptome assembly to produce the first comprehensive
      and integrated genomic resource for yellow horn and identify the pathways and key
      genes related to oil accumulation. In addition, potential molecular markers were
      identified and compiled. METHODOLOGY/PRINCIPAL FINDINGS: Total RNA was isolated
      from 30 plants from two regions, including buds, leaves, flowers and seeds. Equal
      quantities of RNA from these tissues were pooled to construct a cDNA library for
      454 pyrosequencing. A total of 1,147,624 high-quality reads with total and
      average lengths of 530.6 Mb and 462 bp, respectively, were generated. These reads
      were assembled into 51,867 unigenes, corresponding to a total of 36.1 Mb with a
      mean length, N50 and median of 696, 928 and 570 bp, respectively. Of the
      unigenes, 17,541 (33.82%) were unmatched in any public protein databases. We
      identified 281 unigenes that may be involved in de novo fatty acid (FA) and
      triacylglycerol (TAG) biosynthesis and metabolism. Furthermore, 6,707 SSRs,
      16,925 SNPs and 6,201 InDels with high-confidence were also identified in this
      study. CONCLUSIONS: This transcriptome represents a new functional genomics
      resource and a foundation for further studies on the metabolic engineering of
      yellow horn to increase oil content and modify oil composition. The potential
      molecular markers identified in this study provide a basis for polymorphism
      analysis of Xanthoceras, and even Sapindaceae; they will also accelerate the
      process of breeding new varieties with better agronomic characteristics.

PMID- 24040248
TI  - Aluminum hydroxide adjuvant differentially activates the three complement
      pathways with major involvement of the alternative pathway.
AB  - Al(OH)3 is the most common adjuvant in human vaccines, but its mode of action
      remains poorly understood. Complement involvement in the adjuvant properties of
      Al(OH)3 has been suggested in several reports together with a depot effect. It is
      here confirmed that Al(OH)3 treatment of serum depletes complement components and
      activates the complement system. We show that complement activation by Al(OH)3
      involves the three major pathways by monitoring complement components in Al(OH)3
      treated serum and in Al(OH)3-containing precipitates. Al(OH)3 activation of
      complement results in deposition of C3 cleavage products and membrane attack
      complex (MAC) and in generation of the anaphylatoxins C3a and C5a. Complement
      activation was time dependent and inhibited by chelation with EDTA but not
      EGTA+Mg(2+). We thus confirm that Al(OH)3 activates the complement system and
      show that the alternative pathway is of major importance. 

PMID- 24040249
TI  - The asymmetrical effects of divided attention on encoding and retrieval
      processes: a different view based on an interference with the episodic register.
AB  - In this study, we evaluate the conceptualization of encoding and retrieval
      processes established in previous studies that used a divided attention (DA)
      paradigm. These studies indicated that there were considerable detrimental
      effects of DA at encoding on later memory performance, but only minimal effects,
      if any, on divided attention at retrieval. We suggest that this asymmetry in the
      effects of DA on memory can be due, at least partially, to a confound between the
      memory phase (encoding and retrieval) and the memory requirements of the task
      (memory "for" encoded information versus memory "at" test). To control for this
      confound, we tested memory for encoded information and for retrieved information
      by introducing a second test that assessed memory for the retrieved information
      from the first test. We report the results of four experiments that use measures
      of memory performance, retrieval latency, and performance on the concurrent task,
      all of which consistently show that DA at retrieval strongly disrupts later
      memory for the retrieved episode, similarly to the effects of DA at encoding. We
      suggest that these symmetrical disruptive effects of DA at encoding and retrieval
      on later retrieval reflect a disruption of an episodic buffer (EB) or episodic
      register component (ER), rather than a failure of encoding or retrieval
      operations per se. 

PMID- 24040250
TI  - End binding proteins are obligatory dimers.
AB  - End binding (EB) proteins are responsible for the recruitment of an array of
      microtubule plus-end tracking proteins (+TIPs) to growing microtubules ends. EBs
      encompass an N-terminal calponin homology domain that confers microtubule tip
      tracking activity to the protein. The C-terminal domain of EBs contains a coiled
      coil that mediates the parallel dimerization of EB monomers. This part of the
      protein is also responsible for partner binding. While dimerization is not
      essential for microtubule tip tracking by EBs it is a prerequisite for +TIP
      partner binding. The concentration of EBs in cells has been estimated to be in
      the range of hundreds of nanomoles. In contrast, in in vitro single molecule
      experiments EB concentrations of subnanomoles are employed. From a mechanistic
      point of view it is important to assess the oligomerization state of EBs at
      physiologically and experimentally relevant protein concentrations, in particular
      if the goal of a study is to model the behavior of EB-dependent dynamic +TIP
      networks. Here we have determined the stability of the EB1 and EB3 dimers using
      multi-angle light scattering and fluorescence analytical ultracentrifugation. We
      show that these EBs form stable dimers and do not dissociate even at very low
      nanomolar concentrations. The dimers remained stable at both room temperature as
      well as at the physiologically relevant temperature of 37 degrees C. Together,
      our results reveal that EBs are obligatory dimers, a conclusion that has
      implications for the mechanistic understanding of these key proteins involved in
      the orchestration of dynamic protein networks at growing microtubule ends. 

PMID- 24040251
TI  - Visual attention and the neuroimage bias.
AB  - Several highly-cited experiments have presented evidence suggesting that
      neuroimages may unduly bias laypeople's judgments of scientific research. This
      finding has been especially worrisome to the legal community in which neuroimage
      techniques may be used to produce evidence of a person's mental state. However, a
      more recent body of work that has looked directly at the independent impact of
      neuroimages on layperson decision-making (both in legal and more general arenas),
      and has failed to find evidence of bias. To help resolve these conflicting
      findings, this research uses eye tracking technology to provide a measure of
      attention to different visual representations of neuroscientific data. Finding an
      effect of neuroimages on the distribution of attention would provide a potential
      mechanism for the influence of neuroimages on higher-level decisions. In the
      present experiment, a sample of laypeople viewed a vignette that briefly
      described a court case in which the defendant's actions might have been explained
      by a neurological defect. Accompanying these vignettes was either an MRI image of
      the defendant's brain, or a bar graph depicting levels of brain activity-two
      competing visualizations that have been the focus of much of the previous
      research on the neuroimage bias. We found that, while laypeople differentially
      attended to neuroimagery relative to the bar graph, this did not translate into
      differential judgments in a way that would support the idea of a neuroimage bias.

PMID- 24040252
TI  - Recovery of immunological homeostasis positively correlates both with early
      stages of right-colorectal cancer and laparoscopic surgery.
AB  - Differences in postoperative outcome and recovery between patients subjected to
      laparoscopic-assisted versus open surgery for colorectal cancer (CRC) resection
      have been widely documented, though not specifically for right-sided tumors. We
      investigated the immunological responses to the different surgical approaches, by
      comparing postoperative data simultaneously obtained at systemic, local and
      cellular levels. A total of 25 right-sided CRC patients and controls were
      managed, assessing -in the immediate followup- the conventional perioperative
      parameters and a large panel of cytokines on plasma, peritoneal fluids and
      lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC)
      tissue cultures. A general better recovery for patients operated with laparoscopy
      compared to conventional procedure, as indicated by the analysis of typical pre-
      and post-surgical parameters, was observed. The synchronous evaluation of 12
      cytokines showed that preoperative plasma levels of the proinflammatory cytokines
      IL-6, IL-8, IL-1beta, TNFalpha were significantly lower in healthy donors versus
      CRC patients and that such differences progressively increase with tumor stage.
      After surgery, the IL-6 and IL-8 increases were significantly higher in open
      compared to laparoscopic approach only in CRC at early stages. The postsurgical
      whole panel of cytokine levels were significantly higher in peritoneal fluids
      compared to corresponding plasma, but with no significant differences depending
      on kind of surgery or stage of disease. Then we observed that, pre- compared to
      the corresponding post-surgery derived LPS-stimulated PBMC cultures, produced
      higher supernatant levels of the whole cytokine panel. In particular IL-6 in
      vitro production was significantly higher in PBMC derived from patients subjected
      to laparoscopic versus open intervention, but -again- only in CRC at early stages
      of disease. Our results thus show that laparoscopy compared to open right
      resection is associated with a shorter compromission of the immunological
      homeostasis, mainly in early stages of right-CRC patients. 

PMID- 24040253
TI  - Status epilepticus induces vasogenic edema via tumor necrosis factor-alpha/
      endothelin-1-mediated two different pathways.
AB  - Status epilepticus (SE) induces vasogenic edema in the piriform cortex with
      disruptions of the blood-brain barrier (BBB). However, the mechanisms of
      vasogenic edema formation following SE are still unknown. Here we investigated
      the endothelin B (ETB) receptor-mediated pathway of SE-induced vasogenic edema.
      Following SE, the release of tumor necrosis factor-alpha (TNF-alpha) stimulated
      endothelin-1 (ET-1) release and expression in neurons and endothelial cells. In
      addition, TNF-alpha-induced ET-1 increased BBB permeability via ETB receptor
      mediated endothelial nitric oxide synthase (eNOS) activation in endothelial
      cells. ETB receptor activation also increased intracellular reactive oxygen
      species by NADPH oxidase production in astrocytes. These findings suggest that SE
      results in BBB dysfunctions via endothelial-astroglial interactions through the
      TNF-alpha-ET-1-eNOS/NADPH oxidase pathway, and that these ETB receptor-mediated
      interactions may be an effective therapeutic strategy for vasogenic edema in
      various neurological diseases. 

PMID- 24040254
TI  - Opportunistic feeding strategy for the earliest old world hypsodont equids:
      evidence from stable isotope and dental wear proxies.
AB  - BACKGROUND: The equid Hippotherium primigenium, with moderately hypsodont cheek
      teeth, rapidly dispersed through Eurasia in the early late Miocene. This
      dispersal of hipparions into the Old World represents a major faunal event during
      the Neogene. The reasons for this fast dispersal of H. primigenium within Europe
      are still unclear. Based on its hypsodonty, a high specialization in grazing is
      assumed although the feeding ecology of the earliest European hipparionines
      within a pure C3 plant ecosystem remains to be investigated.
      METHODOLOGY/PRINCIPAL FINDINGS: A multi-proxy approach, combining carbon and
      oxygen isotopes from enamel as well as dental meso- and microwear analyses of
      cheek teeth, was used to characterize the diet of the earliest European H.
      primigenium populations from four early Late Miocene localities in Germany
      (Eppelsheim, Howenegg), Switzerland (Charmoille), and France (Soblay). Enamel
      delta(13)C values indicate a pure C3 plant diet with small (<1.40/00) seasonal
      variations for all four H. primigenium populations. Dental wear and carbon
      isotope compositions are compatible with dietary differences. Except for the
      Howenegg hipparionines, dental microwear data indicate a browse-dominated diet.
      By contrast, the tooth mesowear patterns of all populations range from low to
      high abrasion suggesting a wide spectrum of food resources.
      CONCLUSIONS/SIGNIFICANCE: Combined dental wear and stable isotope analysis
      enables refined palaeodietary reconstructions in C3 ecosystems. Different H.
      primigenium populations in Europe had a large spectrum of feeding habits with a
      high browsing component. The combination of specialized phenotypes such as
      hypsodont cheek teeth with a wide spectrum of diet illustrates a new example of
      the Liem's paradox. This dietary flexibility associated with the capability to
      exploit abrasive food such as grasses probably contributed to the rapid dispersal
      of hipparionines from North America into Eurasia and the fast replacement of the
      brachydont equid Anchitherium by the hypsodont H. primigenium in Europe.

PMID- 24040255
TI  - Ephrin-A1 is up-regulated by hypoxia in cancer cells and promotes angiogenesis of
      HUVECs through a coordinated cross-talk with eNOS.
AB  - Hypoxia, ephrin-A1 and endothelial nitric oxide synthase (eNOS) have been proved
      to play critical roles in tumor angiogenesis. However, how ephrin-A1 is regulated
      by hypoxia and whether ephrin-A1 cooperates with eNOS in modulation of
      angiogenesis remain to be addressed in details. Here we demonstrated that both
      ephrin-A1 in squamous cell carcinoma cells (SCC-9) and especially soluble ephrin
      A1 in the supernatants were up-regulated under hypoxic condition. An increased
      nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs)
      was observed in ephrin-A1-induced angiogenesis which was reversed after co
      culture with eNOS specific inhibitor, N-nitro-L-arginine methyl ester
      hydrochloride (L-NAME). Western blot analysis confirmed that both phosphorylation
      of Akt(Ser473) and eNOS(Ser1177) were up-regulated in ephrin-A1-stimulated
      HUVECs, with the total eNOS expression unchanged. The specific inhibitor of
      phosphatidylinositol 3-kinase (PI3K), LY294002, significantly down-regulated
      ephrin-A1-induced expression of phosphorylated Akt(Ser473) as well as
      phosphorylation of eNOS(Ser1177). These results revealed a possible novel
      mechanism whereby ephrin-A1 is regulated in tumor microenvironment and promotes
      angiogenesis through a coordinated cross-talk with PI3K/Akt-dependent eNOS
      activation which may relate to normal vascular development and tumor
      neovascularization.

PMID- 24040256
TI  - A new approach for the study of lung smooth muscle phenotypes and its application
      in a murine model of allergic airway inflammation.
AB  - Phenotypes of lung smooth muscle cells in health and disease are poorly
      characterized. This is due, in part, to a lack of methodologies that allow for
      the independent and direct isolation of bronchial smooth muscle cells (BSMCs) and
      vascular smooth muscle cells (VSMCs) from the lung. In this paper, we describe
      the development of a bi-fluorescent mouse that permits purification of these two
      cell populations by cell sorting. By subjecting this mouse to an acute allergen
      based-model of airway inflammation that exhibits many features of asthma, we
      utilized this tool to characterize the phenotype of so-called asthmatic BSMCs.
      First, we examined the biophysical properties of single BSMCs from allergen
      sensitized mice and found increases in basal tone and cell size that were
      sustained ex vivo. We then generated for the first time, a comprehensive
      characterization of the global gene expression changes in BSMCs isolated from the
      bi-fluorescent mice with allergic airway inflammation. Using statistical methods
      and pathway analysis, we identified a number of differentially expressed mRNAs in
      BSMCs from allergen sensitized mice that code for key candidate proteins
      underlying changes in matrix formation, contractility, and immune responses.
      Ultimately, this tool will provide direction and guidance for the logical
      development of new markers and approaches for studying human lung smooth muscle. 

PMID- 24040258
TI  - Visual search of neuropil-enriched RNAs from brain in situ hybridization data
      through the image analysis pipeline hippo-ATESC.
AB  - MOTIVATION: RNA molecules specifically enriched in the neuropil of neuronal cells
      and in particular in dendritic spines are of great interest for neurobiology in
      virtue of their involvement in synaptic structure and plasticity. The systematic
      recognition of such molecules is therefore a very important task. High resolution
      images of RNA in situ hybridization experiments contained in the Allen Brain
      Atlas (ABA) represent a very rich resource to identify them and have been so far
      exploited for this task through human-expert analysis. However, software tools
      that may automatically address the same objective are not very well developed.
      RESULTS: In this study we describe an automatic method for exploring in situ
      hybridization data and discover neuropil-enriched RNAs in the mouse hippocampus.
      We called it Hippo-ATESC (Automatic Texture Extraction from the Hippocampal
      region using Soft Computing). Bioinformatic validation showed that the Hippo
      ATESC is very efficient in the recognition of RNAs which are manually identified
      by expert curators as neuropil-enriched on the same image series. Moreover, we
      show that our method can also highlight genes revealed by microdissection-based
      methods but missed by human visual inspection. We experimentally validated our
      approach by identifying a non-coding transcript enriched in mouse synaptosomes.
      The code is freely available on the web at
      http://ibislab.ce.unipr.it/software/hippo/.

PMID- 24040257
TI  - Protein similarity networks reveal relationships among sequence, structure, and
      function within the Cupin superfamily.
AB  - The cupin superfamily is extremely diverse and includes catalytically inactive
      seed storage proteins, sugar-binding metal-independent epimerases, and metal
      dependent enzymes possessing dioxygenase, decarboxylase, and other activities.
      Although numerous proteins of this superfamily have been structurally
      characterized, the functions of many of them have not been experimentally
      determined. We report the first use of protein similarity networks (PSNs) to
      visualize trends of sequence and structure in order to make functional inferences
      in this remarkably diverse superfamily. PSNs provide a way to visualize
      relatedness of structure and sequence among a given set of proteins. Structure-
      and sequence-based clustering of cupin members reflects functional clustering.
      Networks based only on cupin domains and networks based on the whole proteins
      provide complementary information. Domain-clustering supports phylogenetic
      conclusions that the N- and C-terminal domains of bicupin proteins evolved
      independently. Interestingly, although many functionally similar enzymatic cupin
      members bind the same active site metal ion, the structure and sequence
      clustering does not correlate with the identity of the bound metal. It is
      anticipated that the application of PSNs to this superfamily will inform
      experimental work and influence the functional annotation of databases. 

PMID- 24040259
TI  - Determination of sRNA expressions by RNA-seq in Yersinia pestis grown in vitro
      and during infection.
AB  - BACKGROUND: Small non-coding RNAs (sRNAs) facilitate host-microbe interactions.
      They have a central function in the post-transcriptional regulation during
      pathogenic lifestyles. Hfq, an RNA-binding protein that many sRNAs act in
      conjunction with, is required for Y. pestis pathogenesis. However, information on
      how Yersinia pestis modulates the expression of sRNAs during infection is largely
      unknown. METHODOLOGY AND PRINCIPAL FINDINGS: We used RNA-seq technology to
      identify the sRNA candidates expressed from Y. pestis grown in vitro and in the
      infected lungs of mice. A total of 104 sRNAs were found, including 26 previously
      annotated sRNAs, by searching against the Rfam database with 78 novel sRNA
      candidates. Approximately 89% (93/104) of these sRNAs from Y. pestis are shared
      with its ancestor Y. pseudotuberculosis. Ninety-seven percent of these sRNAs
      (101/104) are shared among more than 80 sequenced genomes of 135 Y. pestis
      strains. These 78 novel sRNAs include 62 intergenic and 16 antisense sRNAs.
      Fourteen sRNAs were selected for verification by independent Northern blot
      analysis. Results showed that nine selected sRNA transcripts were Hfq-dependent.
      Interestingly, three novel sRNAs were identified as new members of the
      transcription factor CRP regulon. Semi-quantitative analysis revealed that Y.
      pestis from the infected lungs induced the expressions of six sRNAs including
      RyhB1, RyhB2, CyaR/RyeE, 6S RNA, RybB and sR039 and repressed the expressions of
      four sRNAs, including CsrB, CsrC, 4.5S RNA and sR027. CONCLUSIONS AND
      SIGNIFICANCE: This study is the first attempt to subject RNA from Y. pestis
      infected samples to direct high-throughput sequencing. Many novel sRNAs were
      identified and the expression patterns of relevant sRNAs in Y. pestis during in
      vitro growth and in vivo infection were revealed. The annotated sRNAs accounted
      for the most abundant sRNAs either expressed in bacteria grown in vitro or
      differentially expressed in the infected lungs. These findings suggested these
      sRNAs may have important functions in Y. pestis physiology or pathogenesis.

PMID- 24040260
TI  - Four decades of Andean timberline migration and implications for biodiversity
      loss with climate change.
AB  - Rapid 21st-century climate change may lead to large population decreases and
      extinction in tropical montane cloud forest species in the Andes. While prior
      research has focused on species migrations per se, ecotones may respond to
      different environmental factors than species. Even if species can migrate in
      response to climate change, if ecotones do not they can function as hard barriers
      to species migrations, making ecotone migrations central to understanding species
      persistence under scenarios of climate change. We examined a 42-year span of
      aerial photographs and high resolution satellite imagery to calculate migration
      rates of timberline--the grassland-forest ecotone-inside and outside of protected
      areas in the high Peruvian Andes. We found that timberline in protected areas was
      more likely to migrate upward in elevation than in areas with frequent cattle
      grazing and fire. However, rates in both protected (0.24 m yr(-1)) and
      unprotected (0.05 m yr(-1)) areas are only 0.5-2.3% of the rates needed to stay
      in equilibrium with projected climate by 2100. These ecotone migration rates are
      12.5 to 110 times slower than the observed species migration rates within the
      same forest, suggesting a barrier to migration for mid- and high-elevation
      species. We anticipate that the ecotone will be a hard barrier to migration under
      future climate change, leading to drastic population and biodiversity losses in
      the region unless intensive management steps are taken.

PMID- 24040261
TI  - The co-existence of the IL-18+183 A/G and MMP-9 -1562 C/T polymorphisms is
      associated with clinical events in coronary artery disease patients.
AB  - OBJECTIVE: Interleukin (IL)-18 has been associated with severity of
      atherosclerosis and discussed to predict cardiovascular (CV) events. We have
      previously shown that the IL-18+183 G-allele significantly reduces IL-18 levels.
      This study was aimed to investigate the prognostic significance of the IL-18+183
      A/G polymorphism (rs5744292), single and in coexistence with the matrix
      metalloproteinase (MMP)-9 -1562 C/T (rs3918242) polymorphism, in patients with
      stable coronary artery disease (CAD). Serum levels of IL-18, MMP-9 and tissue
      inhibitor of matrix metalloproteinase (TIMP)-1 were additionally assessed.
      METHODS: 1001 patients with angiographically verified CAD were genotyped and the
      biomarkers were measured accordingly. After two years follow-up, 10.6%
      experienced new clinical events; acute myocardial infarction (AMI), stroke,
      unstable angina pectoris and death. RESULTS: The IL-18+183 G-allele associated
      with 35% risk reduction in composite endpoints after adjusting for potential
      covariates (p = 0.044). The IL-18+183 AA/MMP-9 -1562 CT/TT combined genotypes
      associated with a significant increase in risk of composite endpoints (OR = 1.87;
      95% CI = 1.13-3.11, p = 0.015, adjusted). Patients with clinical events presented
      with significantly higher IL-18 levels as compared to patients without (p =
      0.011, adjusted). The upper tertile of IL-18 levels associated with an increase
      in risk of AMI as compared to lower tertiles (OR = 2.36; 95% CI = 1.20-4.64, p =
      0.013, adjusted). CONCLUSION: The IL-18+183 A/G polymorphism, single and in
      combination with MMP-9 genotypes, may influence the risk of clinical events in
      stable CAD patients.

PMID- 24040262
TI  - Boosting BOLD fMRI by K-space density weighted echo planar imaging.
AB  - Functional magnetic resonance imaging (fMRI) has become a powerful and
      influential method to non-invasively study neuronal brain activity. For this
      purpose, the blood oxygenation level-dependent (BOLD) effect is most widely used.
      T2* weighted echo planar imaging (EPI) is BOLD sensitive and the prevailing fMRI
      acquisition technique. Here, we present an alternative to its standard Cartesian
      recordings, i.e. k-space density weighted EPI, which is expected to increase the
      signal-to-noise ratio in fMRI data. Based on in vitro and in vivo pilot
      measurements, we show that fMRI by k-space density weighted EPI is feasible and
      that this new acquisition technique in fact boosted spatial and temporal SNR as
      well as the detection of local fMRI activations. Spatial resolution, spatial
      response function and echo time were identical for density weighted and
      conventional Cartesian EPI. The signal-to-noise ratio gain of density weighting
      can improve activation detection and has the potential to further increase the
      sensitivity of fMRI investigations. 

PMID- 24040263
TI  - MiR-499 regulates cell proliferation and apoptosis during late-stage cardiac
      differentiation via Sox6 and cyclin D1.
AB  - BACKGROUND: MiR-499 is a cardiac-abundant miRNA. However, the biological
      functions of miR-499 in differentiated cardiomyocytes or in the cardiomyocyte
      differentiation process is not very clear. Sox6 is believed to be one of its
      targets, and is also believed to play a role in cardiac differentiation.
      Therefore, our aim was to investigate the association between Sox6 and miR-499
      during cardiac differentiation. METHODOLOGY/PRINCIPAL FINDINGS: Using a well
      established in vitro cardiomyocyte differentiation system, mouse P19CL6 cells, we
      found that miR-499 was highly expressed in the late stage of cardiac
      differentiation. In cells stably transfected with miR-499 (P-499 cells), it was
      found that miR-499 could promote the differentiation into cardiomyocytes at the
      early stage of cardiac differentiation. Notably, cell viability assay, EdU
      incorporation assay, and cell cycle profile analysis all showed that the P-499
      cells displayed the distinctive feature of hyperplastic growth. Further
      investigation confirmed that miR-499 could promote neonatal rat cardiomyocyte
      proliferation. MiR-499 knock-down enhanced apoptosis in the late differentiation
      stage in P19CL6 cells, but overexpression of miR-499 resulted in a decrease in
      the apoptosis rate. Sox6 was identified as a direct target of miR-499 and its
      expression was detected from day 8 or day 10 of cardiac differentiation of P19CL6
      cells. Sox6 played a role in cell viability, inhibited cell proliferation and
      promoted cell apoptosis in P19CL6 cells and cardiomyocytes. The overexpression of
      Sox6 could reverse the proliferation and anti-apoptosis effects of miR-499. It
      was also found that miR-499 might exert its function by regulating cyclin D1 via
      its influence on Sox6. CONCLUSIONS/SIGNIFICANCE: miR-499 probably regulates the
      proliferation and apoptosis of P19CL6 cells in the late stage of cardiac
      differentiation via its effects on Sox6 and cyclin D1.

PMID- 24040264
TI  - The VHSE-based prediction of proteasomal cleavage sites.
AB  - Prediction of proteasomal cleavage sites has been a focus of computational
      biology. Up to date, the predictive methods are mostly based on nonlinear
      classifiers and variables with little physicochemical meanings. In this paper,
      the physicochemical properties of 14 residues both upstream and downstream of a
      cleavage site are characterized by VHSE (principal component score vector of
      hydrophobic, steric, and electronic properties) descriptors. Then, the resulting
      VHSE descriptors are employed to construct prediction models by support vector
      machine (SVM). For both in vivo and in vitro datasets, the performance of VHSE
      based method is comparatively better than that of the well-known PAProC, MAPPP,
      and NetChop methods. The results reveal that the hydrophobic property of 10
      residues both upstream and downstream of the cleavage site is a dominant factor
      affecting in vivo and in vitro cleavage specificities, followed by residue's
      electronic and steric properties. Furthermore, the difference in hydrophobic
      potential between residues flanking the cleavage site is proposed to favor
      substrate cleavages. Overall, the interpretable VHSE-based method provides a
      preferable way to predict proteasomal cleavage sites. 

PMID- 24040265
TI  - Developmental expression of translocator protein/peripheral benzodiazepine
      receptor in reproductive tissues.
AB  - Translocator protein (TSPO) present in the outer mitochondrial membrane has been
      suggested to be critical for cholesterol import, a rate-limiting step for steroid
      hormone biosynthesis. Despite the importance of steroidogenesis in regulating
      reproductive functions, the developmental profile of TSPO expression in the
      gonads and accessory sex organs has not been completely characterized. As a first
      step towards understanding the function of TSPO, we studied its expression in
      male and female murine reproductive organs. We examined testes and ovaries at
      embryonic days 14.5 and 18.5, and postnatal days 0, 7, 14, 21 and 56 of
      development. In the adult testis, TSPO was expressed in both Leydig cells and
      Sertoli cells. In the developing testes TSPO expression was seen in immature
      Sertoli cells, fetal Leydig cells and gonocytes. In the ovary, TSPO was expressed
      in the ovarian surface epithelium, interstitial cells granulosa cells and luteal
      cells. Corpora lutea of ovaries from pregnant mice showed strong expression of
      TSPO. In the developing ovary, TSPO expression was seen in the squamous
      pregranulosa cells associated with germ line cysts, together with progressively
      increasing expression in interstitial cells and the ovarian surface epithelium.
      In adult mice, the epithelia of other reproductive tissues like the epididymis,
      prostate, seminal vesicle, oviduct and uterus also showed distinct patterns of
      TSPO expression. In summary, TSPO expression in both male and female reproductive
      tissues was not only restricted to steroidogenic cells. Expression in Sertoli
      cells, ovarian surface epithelium, efferent ductal epithelium, prostatic
      epithelium, seminal vesiclular epithelium, uterine epithelium and oviductal
      epithelium suggest either previously unknown sites for de novo steroidogenesis or
      functions for TSPO distinct from its well-studied role in steroid hormone
      production. 

PMID- 24040266
TI  - Regulation of dopamine D1 receptor dynamics within the postsynaptic density of
      hippocampal glutamate synapses.
AB  - Dopamine receptor potently modulates glutamate signalling, synaptic plasticity
      and neuronal network adaptations in various pathophysiological processes.
      Although key intracellular signalling cascades have been identified, the cellular
      mechanism by which dopamine and glutamate receptor-mediated signalling interplay
      at glutamate synapse remain poorly understood. Among the cellular mechanisms
      proposed to aggregate D1R in glutamate synapses, the direct interaction between
      D1R and the scaffold protein PSD95 or the direct interaction with the glutamate
      NMDA receptor (NMDAR) have been proposed. To tackle this question we here used
      high-resolution single nanoparticle imaging since it provides a powerful way to
      investigate at the sub-micron resolution the dynamic interaction between these
      partners in live synapses. We demonstrate in hippocampal neuronal networks that
      dopamine D1 receptors (D1R) laterally diffuse within glutamate synapses, in which
      their diffusion is reduced. Disrupting the interaction between D1R and PSD95,
      through genetical manipulation and competing peptide, did not affect D1R dynamics
      in glutamatergic synapses. However, preventing the physical interaction between
      D1R and the GluN1 subunit of NMDAR abolished the synaptic stabilization of
      diffusing D1R. Together, these data provide direct evidence that the interaction
      between D1R and NMDAR in synapses participate in the building of the dopamine
      receptor-mediated signalling, and most likely to the glutamate-dopamine cross
      talk. 

PMID- 24040267
TI  - Export of extracellular polysaccharides modulates adherence of the Cyanobacterium
      synechocystis.
AB  - The field of cyanobacterial biofuel production is advancing rapidly, yet we know
      little of the basic biology of these organisms outside of their photosynthetic
      pathways. We aimed to gain a greater understanding of how the cyanobacterium
      Synechocystis PCC 6803 (Synechocystis, hereafter) modulates its cell surface.
      Such understanding will allow for the creation of mutants that autoflocculate in
      a regulated way, thus avoiding energy intensive centrifugation in the creation of
      biofuels. We constructed mutant strains lacking genes predicted to function in
      carbohydrate transport or synthesis. Strains with gene deletions of slr0977
      (predicted to encode a permease component of an ABC transporter), slr0982
      (predicted to encode an ATP binding component of an ABC transporter) and slr1610
      (predicted to encode a methyltransferase) demonstrated flocculent phenotypes and
      increased adherence to glass. Upon bioinformatic inspection, the gene products of
      slr0977, slr0982, and slr1610 appear to function in O-antigen (OAg) transport and
      synthesis. However, the analysis provided here demonstrated no differences
      between OAg purified from wild-type and mutants. However, exopolysaccharides
      (EPS) purified from mutants were altered in composition when compared to wild
      type. Our data suggest that there are multiple means to modulate the cell surface
      of Synechocystis by disrupting different combinations of ABC transporters and/or
      glycosyl transferases. Further understanding of these mechanisms may allow for
      the development of industrially and ecologically useful strains of cyanobacteria.
      Additionally, these data imply that many cyanobacterial gene products may possess
      as-yet undiscovered functions, and are meritorious of further study. 

PMID- 24040268
TI  - Role of phosphatidylinositol 4,5-bisphosphate in regulating EHD2 plasma membrane
      localization.
AB  - The four mammalian C-terminal Eps15 homology domain-containing proteins (EHD1
      EHD4) play pivotal roles in endocytic membrane trafficking. While EHD1, EHD3 and
      EHD4 associate with intracellular tubular/vesicular membranes, EHD2 localizes to
      the inner leaflet of the plasma membrane. Currently, little is known about the
      regulation of EHD2. Thus, we sought to define the factors responsible for EHD2's
      association with the plasma membrane. The subcellular localization of endogenous
      EHD2 was examined in HeLa cells using confocal microscopy. Although EHD partner
      proteins typically mediate EHD membrane recruitment, EHD2 was targeted to the
      plasma membrane independent of two well-characterized binding proteins, syndapin2
      and EHBP1. Additionally, the EH domain of EHD2, which facilitates canonical EHD
      protein interactions, was not required to direct overexpressed EHD2 to the cell
      surface. On the other hand, several lines of evidence indicate that the plasma
      membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) plays a
      crucial role in regulating EHD2 subcellular localization. Pharmacologic
      perturbation of PIP2 metabolism altered PIP2 plasma membrane distribution (as
      assessed by confocal microscopy), and caused EHD2 to redistribute away from the
      plasma membrane. Furthermore, overexpressed EHD2 localized to PIP2-enriched
      vacuoles generated by active Arf6. Finally, we show that although cytochalasin D
      caused actin microfilaments to collapse, EHD2 was nevertheless maintained at the
      plasma membrane. Intriguingly, cytochalasin D induced relocalization of both PIP2
      and EHD2 to actin aggregates, supporting a role of PIP2 in controlling EHD2
      subcellular localization. Altogether, these studies emphasize the significance of
      membrane lipid composition for EHD2 subcellular distribution and offer new
      insights into the regulation of this important endocytic protein. 

PMID- 24040269
TI  - Dynamic edge effects in small mammal communities across a conservation
      agricultural interface in Swaziland.
AB  - Across the planet, high-intensity farming has transformed native vegetation into
      monocultures, decreasing biodiversity on a landscape scale. Yet landscape-scale
      changes to biodiversity and community structure often emerge from processes
      operating at local scales. One common process that can explain changes in
      biodiversity and community structure is the creation of abrupt habitat edges,
      which, in turn, generate edge effects. Such effects, while incredibly common, can
      be highly variable across space and time; however, we currently lack a general
      analytical framework that can adequately capture such spatio-temporal
      variability. We extend previous approaches for estimating edge effects to a non
      linear mixed modeling framework that captures such spatio-temporal heterogeneity
      and apply it to understand how agricultural land-uses alter wildlife communities.
      We trapped small mammals along a conservation-agriculture land-use interface
      extending 375 m into sugarcane plantations and conservation land-uses at three
      sites during dry and wet seasons in Swaziland, Africa. Sugarcane plantations had
      significant reductions in species richness and heterogeneity, and showed an
      increase in community similarity, suggesting a more homogenized small mammal
      community. Furthermore, our modeling framework identified strong variation in
      edge effects on communities across sites and seasons. Using small mammals as an
      indicator, intensive agricultural practices appear to create high-density
      communities of generalist species while isolating interior species in less than
      225 m. These results illustrate how agricultural land-use can reduce diversity
      across the landscape and that effects can be masked or magnified, depending on
      local conditions. Taken together, our results emphasize the need to create or
      retain natural habitat features in agricultural mosaics. 

PMID- 24040270
TI  - Grape powder intake prevents ovariectomy-induced anxiety-like behavior, memory
      impairment and high blood pressure in female Wistar rats.
AB  - Diminished estrogen influence at menopause is reported to be associated with
      cognitive decline, heightened anxiety and hypertension. While estrogen therapy is
      often prescribed to overcome these behavioral and physiological deficits,
      antioxidants which have been shown beneficial are gaining nutritional
      intervention and popularity. Therefore, in the present study, utilizing the
      antioxidant properties of grapes, we have examined effect of 3 weeks of grape
      powder (GP; 15 g/L dissolved in tap water) treatment on anxiety-like behavior,
      learning-memory impairment and high blood pressure in ovariectomized (OVX) rats.
      Four groups of female Wistar rats were used; sham control, sham-GP treated, OVX
      and OVX+GP treated. We observed a significant increase in systolic and diastolic
      blood pressure in OVX rats as compared to sham-controls. Furthermore, ovariectomy
      increased anxiety-like behavior and caused learning and memory impairment in rats
      as compared to sham-controls. Interestingly, providing grape powder treated water
      to OVX rats restored both systolic and diastolic blood pressure, decreased
      anxiety-like behavior and improved memory function. Moreover, OVX rats exhibited
      an impaired long term potentiation which was restored with grape powder
      treatment. Furthermore, ovariectomy increased oxidative stress in the brain,
      serum and urine, selectively decreasing antioxidant enzyme, glyoxalase-1 protein
      expression in the hippocampus but not in the cortex and amygdala of OVX rats,
      while grape powder treatment reversed these effects. Other antioxidant enzyme
      levels, including manganese superoxide dismutase (SOD) and Cu/Zn SOD remained
      unchanged. We suggest that grape powder by regulating oxidative stress mechanisms
      exerts its protective effect on blood pressure, learning-memory and anxiety-like
      behavior. Our study is the first to examine behavioral, biochemical,
      physiological and electrophysiological outcome of estrogen depletion in rats and
      to test protective role of grape powder, all in the same study. 

PMID- 24040271
TI  - Aberrant expression of Cx43 is associated with the peritoneal metastasis of
      gastric cancer and Cx43-mediated gap junction enhances gastric cancer cell
      diapedesis from peritoneal mesothelium.
AB  - The process of peritoneal metastasis involves the diapedesis of intra-abdominal
      exfoliated gastric cancer cells through the mesothelial cell monolayers; however,
      the related molecular mechanisms for this process are still unclear.
      Heterocellular gap-junctional intercellular communication (GJIC) between gastric
      cancer cells and mesothelial cells may play an active role during diapedesis. In
      this study we detected the expression of connexin 43 (Cx43) in primary gastric
      cancer tissues, intra-abdominal exfoliated cancer cells, and matched metastatic
      peritoneal tissues. We found that the expression of Cx43 in primary gastric
      cancer tissues was significantly decreased; the intra-abdominal exfoliated cancer
      cells and matched metastatic peritoneal tissues exhibited increasing expression
      compared with primary gastric cancer tissues. BGC-823 and SGC-7901 human gastric
      cancer cells were engineered to express Cx43 or Cx43T154A (a mutant protein that
      only couples gap junctions but provides no intercellular communication) and were
      co-cultured with human peritoneal mesothelial cells (HPMCs). Heterocellular GJIC
      and diapedesis through HPMC monolayers on matrigel-coated coverslips were
      investigated. We found that BGC-823 and SGC-7901 gastric cancer cells expressing
      Cx43 formed functional heterocellular gap junctions with HPMC monolayers within
      one hour. A significant increase in diapedesis was observed in engineered Cx43
      expressing cells compared with Cx43T154A and control group cells, which suggested
      that the observed upregulation of diapedesis in Cx43-expressing cells required
      heterocellular GJIC. Further study revealed that the gastric cancer cells
      transmigrated through the intercellular space between the mesothelial cells via a
      paracellular route. Our results suggest that the abnormal expression of Cx43
      plays an essential role in peritoneal metastasis and that Cx43-mediated
      heterocellular GJIC between gastric cancer cells and mesothelial cells may be an
      important regulatory step during metastasis. Finally, we observed that the
      diapedesis of exfoliated gastric cancer cells through mesothelial barriers is a
      viable route of paracellular migration. 

PMID- 24040272
TI  - Transgenerational shifts in reproduction hormesis in green peach aphid exposed to
      low concentrations of imidacloprid.
AB  - Hormesis is a biphasic phenomenon that in toxicology is characterized by low-dose
      stimulation and high-dose inhibition. It has been observed in a wide range of
      organisms in response to many chemical stressors, including insects exposed to
      pesticides, with potential repercussions for agriculture and pest management. To
      address questions related to the nature of the dose-response and potential
      consequences on biological fitness, we examined transgenerational hormesis in the
      green peach aphid, Myzus persicae, when exposed to sublethal concentrations of
      the insecticide imidacloprid. A hormetic response in the form of increased
      reproduction was consistently observed and a model previously developed to test
      for hormesis adequately fit some of our data. However, the nature of the dose
      response differed within and across generations depending upon the duration and
      mode of exposure. Decreased reproduction in intermediate generations confirmed
      that fitness tradeoffs were a consequence of the hormetic response. However,
      recovery to levels of reproduction equal to that of controls in subsequent
      generations and significantly greater total reproduction after four generations
      suggested that biological fitness was increased by exposure to low concentrations
      of the insecticide, even when insects were continuously exposed to the stressor.
      This was especially evident in a greenhouse experiment where the instantaneous
      rate of population increase almost doubled and total aphid production more than
      quadrupled when aphids were exposed to potato plants systemically treated with
      low amounts of imidacloprid. Our results show that although fitness tradeoffs do
      occur with hormetic responses, this does not necessarily compromise overall
      biological fitness. 

PMID- 24040273
TI  - Disruption of persistent nociceptive behavior in rats with learning impairment.
AB  - Despite the subjective nature of pain experience with cognitive and affective
      dimensions, preclinical pain research has largely focused on its sensory
      dimension. Here, we examined the relationship between learning/memory and
      nociceptive behavior in rats with combined learning impairment and persistent
      nociception. Learning impairment was induced by bilateral hippocampal injection
      of a mixed Abeta solution, whereas persistent nociception produced in these rats
      by complete Freund's adjuvant-induced ankle inflammation. Those rats with
      learning impairment showed a diminished development of thermal hyperalgesia and
      mechanical allodynia and a shorter time course of nociceptive behavior without
      alteration of their baseline nociceptive threshold. In rats with pre-established
      hyperalgesia and allodynia due to ankle inflammation, bilateral intra-hippocampal
      injection of cycloheximide (a protein synthesis inhibitor) promoted the earlier
      recovery of nociceptive behavior. Moreover, expression of Abeta, NR1 subunit of
      the N-methyl-D-aspartate receptor, and protein kinase Cgamma was upregulated,
      whereas the choline acetyl transferase expression was downregulated, in the
      hippocampus, thalamus, amygdala, and/or spinal cord of rats with combined
      learning impairment and persistent nociception. The data indicate that learning
      impairment could disrupt the response to a state of persistent nociception,
      suggesting an important role for cognitive maladaptation in the mechanisms of
      chronic pain. These results also suggest that a preclinical model of combined
      learning impairment and persistent nociception may be useful to explore the brain
      mechanisms underlying the transition from acute to chronic pain. 

PMID- 24040274
TI  - A research study of the association between maternal microchimerism and systemic
      lupus erythematosus in adults: a comparison between patients and healthy controls
      based on single-nucleotide polymorphism using quantitative real-time PCR.
AB  - BACKGROUND: Naturally acquired microchimerism may arise in the mother and her
      child during pregnancy when bidirectional trafficking of cells occurs through the
      placental barrier. The occurrence of maternal microchimerism (maternal cells in
      the offspring) has been associated with several autoimmune diseases, especially
      in children. Systemic Lupus erythematosus (SLE) is an autoimmune disorder with a
      resemblance to graft-versus-host disease. The aim of this study was to
      investigate the association between maternal microchimerism in the blood and SLE.
      METHODOLOGY/PRINCIPAL FINDINGS: Thirty-two patients with SLE, 17 healthy brothers
      of the patients, and an additional 12 unrelated healthy men were the subjects in
      this study. A single-nucleotide polymorphism unique to each mother was
      identified, and maternal microchimerism in the study group and in the control
      group was detected using a quantitative real-time polymerase chain reaction
      technique. No differences in the frequency or the concentration of maternal cells
      were apparent in the blood of patients with SLE or in that of the controls. Two
      patients and one control tested positive for maternal microchimerism, but the
      positive subjects were all negative at a follow-up 16 years later. The
      sensitivity of the method was estimated to 1/10.000. CONCLUSIONS/SIGNIFICANCE:
      These results show no association between SLE and maternal microchimerism. The
      frequency of maternal microchimerism in the blood of adults overall may be lower
      than earlier reported.

PMID- 24040275
TI  - Senescent cardiac fibroblast is critical for cardiac fibrosis after myocardial
      infarction.
AB  - Senescence is a recognized mechanism of cardiovascular diseases; however, its
      contribution to myocardial fibrosis and rupture after infarction and the
      underlying mechanisms remain unclear. Here we showed that senescent cardiac
      fibroblasts markedly accumulated in heart after myocardial infarction. The
      expression of key senescence regulators, especially p53, was significantly up
      regulated in the infarcted heart or hypoxia-treated fibroblasts. Furthermore,
      knockdown of endogenous p53 by siRNA in fibroblasts markedly reduced hypoxia
      induced cell senescence, cytokine expression but increased collagen expression,
      whereas increased expression of p53 protein by adenovirus infection had opposite
      effects. Consistent with in vitro results in cardiac fibroblasts, p53 deficiency
      in vivo significantly decreased the accumulation of senescent fibroblasts, the
      infiltration of macrophages and matrix metalloproteinases, but enhanced collagen
      deposition after myocardial infarction. In conclusion, these results suggest that
      the p53-mediated fibroblast senescence limits cardiac collagen production, and
      inhibition of p53 activity could represent a novel therapeutic target to increase
      reparative fibrosis and to prevent heart rupture after myocardial infarction. 

PMID- 24040276
TI  - Face recognition deficits in autism spectrum disorders are both domain specific
      and process specific.
AB  - Although many studies have reported face identity recognition deficits in autism
      spectrum disorders (ASD), two fundamental question remains: 1) Is this deficit
      "process specific" for face memory in particular, or does it extend to perceptual
      discrimination of faces as well? And 2) Is the deficit "domain specific" for
      faces, or is it found more generally for other social or even nonsocial stimuli?
      The answers to these questions are important both for understanding the nature of
      autism and its developmental etiology, and for understanding the functional
      architecture of face processing in the typical brain. Here we show that children
      with ASD are impaired (compared to age and IQ-matched typical children) in face
      memory, but not face perception, demonstrating process specificity. Further, we
      find no deficit for either memory or perception of places or cars, indicating
      domain specificity. Importantly, we further showed deficits in both the
      perception and memory of bodies, suggesting that the relevant domain of deficit
      may be social rather than specifically facial. These results provide a more
      precise characterization of the cognitive phenotype of autism and further
      indicate a functional dissociation between face memory and face perception.

PMID- 24040277
TI  - Simvastatin induced neurite outgrowth unveils role of cell surface cholesterol
      and acetyl CoA carboxylase in SH-SY5Y cells.
AB  - Statins are known to modulate cell surface cholesterol (CSC) and AMP-activated
      protein kinase (AMPK) in non-neural cells; however no study demonstrates whether
      CSC and AMPK may regulate simvastatin induced neuritogenesis (SIN). We found that
      simvastatin (SIM) maintains CSC as shown by Fillipin III staining, Flotillin-2
      protein expression / localization and phosphorylation of various receptor
      tyrosine kinases (RTKs) in the plasma membrane. Modulation of CSC revealed that
      SIN is critically dependent on this CSC. Simultaneously, phospho array for
      mitogen activated protein kinases (MAPKs) revealed PI3K / Akt as intracellular
      pathway which modulates lipid pathway by inhibiting AMPK activation. Though, SIM
      led to a transient increase in AMPK phosphorylation followed by a sudden decline;
      the effect was independent of PI3K. Strikingly, AMPK phosphorylation was
      regulated by protein phosphatase 2A (PP2A) activity which was enhanced upon SIM
      treatment as evidenced by increase in threonine phosphorylation. Moreover, it was
      observed that addition of AMP analogue and PP2A inhibitor inhibited SIN. Bio
      composition of neurites shows that lipids form a major part of neurites and AMPK
      is known to regulate lipid metabolism majorly through acetyl CoA carboxylase
      (ACC). AMPK activity is negative regulator of ACC activity and we found that
      phosphorylation of ACC started to decrease after 6 hrs which becomes more
      pronounced at 12 hrs. Addition of ACC inhibitor showed that SIN is dependent on
      ACC activity. Simultaneously, addition of Fatty acid synthase (FAS) inhibitor
      confirmed that endogenous lipid pathway is important for SIN. We further
      investigated SREBP-1 pathway activation which controls ACC and FAS at
      transcriptional level. However, SIM did not affect SREBP-1 processing and
      transcription of its target genes likes ACC1 and FAS. In conclusion, this study
      highlights a distinct role of CSC and ACC in SIN which might have implication in
      process of neuronal differentiation induced by other agents. 

PMID- 24040278
TI  - Reasons for non-completion of health related quality of life evaluations in
      pediatric acute myeloid leukemia: a report from the Children's Oncology Group.
AB  - BACKGROUND: Health related quality of life (HRQL) assessments during therapy for
      pediatric cancer are important. The objective of this study was to describe
      reasons for failure to provide HRQL assessments during a pediatric acute myeloid
      leukemia (AML) clinical trial. METHODS: We focused on HRQL assessments embedded
      in a multicenter pediatric AML clinical trial. The PedsQL 4.0 Generic Core
      Scales, PedsQL 3.0 Acute Cancer Module, PedsQL Multidimensional Fatigue Scale,
      and Pediatric Inventory for Parents were obtained from parent/guardian
      respondents at a maximum of six time points. Children provided self-report
      optionally. A central study coordinator contacted sites with delinquent HRQL
      data. Reasons for failure to submit the HRQL assessments were evaluated by three
      pediatric oncologists and themes were generated using thematic analysis. RESULTS:
      There were 906 completed and 1091 potential assessments included in this analysis
      (83%). The median age of included children was 12.9 years (range 2.0 to 18.9).
      The five themes for non-completion were: patient too ill; passive or active
      refusal by respondent; developmental delay; logistical challenges; and poor
      knowledge of study processes from both the respondent and institutional
      perspective. CONCLUSIONS: We identified reasons for non-completion of HRQL
      assessments during active therapy. This information will facilitate
      recommendations to improve study processes and future HRQL study designs to
      maximize response rates.

PMID- 24040279
TI  - Beneficial effects of wheat gluten hydrolysate to extend lifespan and induce
      stress resistance in nematode Caenorhabditis elegans.
AB  - Previous studies have showed that wheat gluten hydrolysate (WGH) has the anti
      oxidative property. In the present study, we examined the possible safety
      property of WGH and the beneficial effects of WGH to extend lifespan and induce
      stress resistance using nematode Caenorhabditis elegans as the in vivo assay
      system. We found that WGH at concentrations of 0.1-1 mg/mL did not cause
      lethality, influence development, alter locomotion behavior and brood size, and
      induce significant intestinal autofluorescence and reactive oxygen species (ROS)
      production in young adults. Treatment with 0.1-1 mg/mL of WGH significantly
      extended lifespans of nematodes under the normal conditions. Moreover, WGH
      treatment significantly inhibited the induction of intestinal autofluorescence
      and suppressed the decrease in locomotion behavior during the aging process of
      nematodes. Furthermore, pre-treatment with 1 mg/mL of WGH significantly
      suppressed the adverse effects caused by heat-stress or oxidative stress on
      nematodes as indicated by the alterations of both lifespan and intestinal ROS
      production. Therefore, WGH treatment is relatively safe and has beneficial
      effects on nematodes under both the normal conditions and the stress conditions. 

PMID- 24040280
TI  - In vivo activity and pharmacokinetics of nemorosone on pancreatic cancer
      xenografts.
AB  - Pancreatic cancer is one of the leading cancer-related causes of death in the
      western world with an urgent need for new treatment strategies. Recently,
      hyperforin and nemorosone have been described as promising anti-cancer lead
      compounds. While hyperforin has been thoroughly investigated in vitro and in
      vivo, in vivo data for nemorosone are still missing. Thus, we investigated the
      growth-inhibitory potential of nemorosone on pancreatic cancer xenografts in NMRI
      nu/nu mice and determined basic pharmacokinetic parameters. Xenograft tumors were
      treated with nemorosone and gemcitabine, the current standard of care. Tumor
      sections were subjected to H&E as well as caspase 3 and Ki-67 staining.
      Nemorosone plasma kinetics were determined by HPLC and mass spectrometry.
      Induction of CYP3A4 and other metabolizing enzymes by nemorosone and hyperforin
      was tested on primary hepatocytes using qRT-PCR. At a dose of 50 mg/kg nemorosone
      per day, a significant growth-inhibitory effect was observed in pancreatic cancer
      xenografts. The compound was well tolerated and rapidly absorbed into the
      bloodstream with a half-life of approximately 30 min. Different metabolites were
      detected, possibly resembling CYP3A4-independent oxidation products. It is
      concluded that nemorosone is a potential anti-cancer lead compound with good
      bioavailability, little side-effects and promising growth-inhibitory effects,
      thus representing a valuable compound for a combination therapy approach. 

PMID- 24040281
TI  - Chromatin changes in dicer-deficient mouse embryonic stem cells in response to
      retinoic acid induced differentiation.
AB  - Loss of Dicer, an enzyme critical for microRNA biogenesis, results in lethality
      due to a block in mouse embryonic stem cell (mES) differentiation. Using ChIP-Seq
      we found increased H3K9me2 at over 900 CpG islands in the Dicer(-/-)ES epigenome.
      Gene ontology analysis revealed that promoters of chromatin regulators to be
      among the most impacted by increased CpG island H3K9me2 in ES (Dicer(-/-)). We
      therefore, extended the study to include H3K4me3 and H3K27me3 marks for selected
      genes. We found that the ES (Dicer(-/-)) mutant epigenome was characterized by a
      shift in the overall balance between transcriptionally favorable (H3K4me3) and
      unfavorable (H3K27me3) marks at key genes regulating ES cell differentiation.
      Pluripotency genes Oct4, Sox2 and Nanog were not impacted in relation to patterns
      of H3K27me3 and H3K4me3 and showed no changes in the rates of transcript down
      regulation in response to RA. The most striking changes were observed in regards
      to genes regulating differentiation and the transition from self-renewal to
      differentiation. An increase in H3K4me3 at the promoter of Lin28b was associated
      with the down-regulation of this gene at a lower rate in Dicer(-/-)ES as compared
      to wild type ES. An increase in H3K27me3 in the promoters of differentiation
      genes Hoxa1 and Cdx2 in Dicer(-/-)ES cells was coincident with an inability to up
      regulate these genes at the same rate as ES upon retinoic acid (RA)-induced
      differentiation. We found that siRNAs Ezh2 and post-transcriptional silencing of
      Ezh2 by let-7 g rescued this effect suggesting that Ezh2 up-regulation is in part
      responsible for increased H3K27me3 and decreased rates of up-regulation of
      differentiation genes in Dicer(-/-)ES.

PMID- 24040283
TI  - The relative importance of Janzen-Connell effects in influencing the spatial
      patterns at the Gutianshan subtropical forest.
AB  - The Janzen-Connell hypothesis is among the most important theories put forward to
      explain species coexistence in species-rich communities. However, the relative
      importance of Janzen-Connell effects with respect to other prominent mechanisms
      of community assembly, such as dispersal limitation, self-thinning due to
      competition, or habitat association, is largely unresolved. Here we use data from
      a 24-ha Gutianshan subtropical forest to address it. First we tested for
      significant associations of adults, juveniles, and saplings with environmental
      variables. Second we evaluated if aggregation decreased with life stage. In a
      third analysis we approximately factored out the effect of habitat association
      and comprehensively analyzed the spatial associations of intraspecific adults and
      offspring (saplings, juveniles) of 46 common species at continuous neighborhood
      distances. We found i) that, except for one, all species were associated with at
      least one environmental variable during at least one of their life stages, but
      the frequency of significant habitat associations declined with increasing life
      stage; ii) a decline in aggregation with increasing life stage that was strongest
      from juveniles to adults; and iii) intraspecific adult-offspring associations
      were dominated by positive relationships at neighborhood distances up to 10 m.
      Our results suggest that Janzen-Connell effects were not the dominant mechanisms
      in structuring the spatial patterns of established trees in the subtropical
      Gutianshan forest. The spatial patterns may rather reflect the joint effects of
      size-dependent self-thinning, dispersal limitation and habitat associations. Our
      findings contribute to a more comprehensive understanding of the relative
      importance of Janzen-Connell effects in influencing plant community structure
      under strong topographic heterogeneity. 

PMID- 24040282
TI  - Meta-regression analyses, meta-analyses, and trial sequential analyses of the
      effects of supplementation with beta-carotene, vitamin A, and vitamin E singly or
      in different combinations on all-cause mortality: do we have evidence for lack of
      harm?
AB  - BACKGROUND AND AIMS: Evidence shows that antioxidant supplements may increase
      mortality. Our aims were to assess whether different doses of beta-carotene,
      vitamin A, and vitamin E affect mortality in primary and secondary prevention
      randomized clinical trials with low risk of bias. METHODS: The present study is
      based on our 2012 Cochrane systematic review analyzing beneficial and harmful
      effects of antioxidant supplements in adults. Using random-effects meta-analyses,
      meta-regression analyses, and trial sequential analyses, we examined the
      association between beta-carotene, vitamin A, and vitamin E, and mortality
      according to their daily doses and doses below and above the recommended daily
      allowances (RDA). RESULTS: We included 53 randomized trials with low risk of bias
      (241,883 participants, aged 18 to 103 years, 44.6% women) assessing beta
      carotene, vitamin A, and vitamin E. Meta-regression analysis showed that the dose
      of vitamin A was significantly positively associated with all-cause mortality.
      Beta-carotene in a dose above 9.6 mg significantly increased mortality (relative
      risk (RR) 1.06, 95% confidence interval (CI) 1.02 to 1.09, I(2) = 13%). Vitamin A
      in a dose above the RDA (> 800 ug) did not significantly influence mortality (RR
      1.08, 95% CI 0.98 to 1.19, I(2) = 53%). Vitamin E in a dose above the RDA (> 15
      mg) significantly increased mortality (RR 1.03, 95% CI 1.00 to 1.05, I(2) = 0%).
      Doses below the RDAs did not affect mortality, but data were sparse. CONCLUSIONS:
      Beta-carotene and vitamin E in doses higher than the RDA seem to significantly
      increase mortality, whereas we lack information on vitamin A. Dose of vitamin A
      was significantly associated with increased mortality in meta-regression. We lack
      information on doses below the RDA. BACKGROUND: All essential compounds to stay
      healthy cannot be synthesized in our body. Therefore, these compounds must be
      taken through our diet or obtained in other ways [1]. Oxidative stress has been
      suggested to cause a variety of diseases [2]. Therefore, it is speculated that
      antioxidant supplements could have a potential role in preventing diseases and
      death. Despite the fact that a normal diet in high-income countries may provide
      sufficient amounts of antioxidants [3,4], more than one third of adults regularly
      take antioxidant supplements [5,6].

PMID- 24040284
TI  - BAD dephosphorylation and decreased expression of MCL-1 induce rapid apoptosis in
      prostate cancer cells.
AB  - PTEN loss and constitutive activation of the PI3K signaling pathway have been
      associated with advanced androgen-independent prostate cancer. PTEN-deficient
      prostate cancer C42Luc cells survive in serum-free media and show relative
      resistance to apoptosis even in the presence of the PI3K inhibitor ZSTK474. Yet,
      when ZSTK474 is combined with the translation inhibitor cycloheximide, C42Luc
      cells undergo apoptosis within 6 hours. We identified dephosphorylation of BAD
      (Bcl2-associated death promoter) as a main apoptosis-regulatory molecule
      downstream from PI3K, and loss of MCL-1 (Myeloid cell leukemia -1) as a major
      target of cycloheximide. The combination of MCL-1 knockdown and expression of
      phosphorylation-deficient mutant BAD2SA is sufficient to trigger rapid apoptosis
      in prostate cancer cells. These results establish the mechanism for the
      synergistic induction of apoptosis by the combination of a PI3K inhibitor and of
      a protein synthesis inhibitor in PTEN-deficient prostate cancer cells. 

PMID- 24040285
TI  - Integrative bioinformatics links HNF1B with clear cell carcinoma and tumor
      associated thrombosis.
AB  - Clear cell carcinoma (CCC) is a histologically distinct carcinoma subtype that
      arises in several organ systems and is marked by cytoplasmic clearing, attributed
      to abundant intracellular glycogen. Previously, transcription factor hepatocyte
      nuclear factor 1-beta (HNF1B) was identified as a biomarker of ovarian CCC. Here,
      we set out to explore more broadly the relation between HNF1B and carcinomas with
      clear cell histology. HNF1B expression, evaluated by immunohistochemistry, was
      significantly associated with clear cell histology across diverse gynecologic and
      renal carcinomas (P<0.001), as was hypomethylation of the HNF1B promoter
      (P<0.001). From microarray analysis, an empirically-derived HNF1B signature was
      significantly enriched for computationally-predicted targets (with HNF1 binding
      sites) (P<0.03), as well as genes associated with glycogen metabolism, including
      glucose-6-phophatase, and strikingly the blood clotting cascade, including
      fibrinogen, prothrombin and factor XIII. Enrichment of the clotting cascade was
      also evident in microarray data from ovarian CCC versus other histotypes
      (P<0.01), and HNF1B-associated prothrombin expression was verified by
      immunohistochemistry (P = 0.015). Finally, among gynecologic carcinomas with
      cytoplasmic clearing, HNF1B immunostaining was linked to a 3.0-fold increased
      risk of clinically-significant venous thrombosis (P = 0.043), and with a 2.3-fold
      increased risk (P = 0.011) in a combined gynecologic and renal carcinoma cohort.
      Our results define HNF1B as a broad marker of clear cell phenotype, and support a
      mechanistic link to glycogen accumulation and thrombosis, possibly reflecting
      (for gynecologic CCC) derivation from secretory endometrium. Our findings also
      implicate a novel mechanism of tumor-associated thrombosis (a major cause of
      cancer mortality), based on the direct production of clotting factors by cancer
      cells.

PMID- 24040286
TI  - Metabolic health is more closely associated with coronary artery calcification
      than obesity.
AB  - BACKGROUND: Recent studies have suggested that metabolic health may contribute
      more to the atherosclerosis than obesity. The aim of this study is to compare
      coronary artery calcium scores (CACS) among patients with different metabolic
      health and obesity status. METHODS: A health-screening program of 24,063
      participants (mean age 41 years) was conducted, and CACS was assessed by multi
      detector computerized tomography (MDCT). Being metabolically healthy was defined
      as having fewer than two of the following risk factors: high blood pressure, high
      fasting blood glucose, high triglyceride, low high-density lipoprotein
      cholesterol, highest decile of homeostasis model assessment-insulin resistance
      (HOMA-IR) index, and highest decile of high-sensitivity C-reactive protein (hs
      CRP). Obesity status was defined as body mass index (BMI) higher than 25 kg/m(2).
      Analyses were performed in four groups divided according to metabolic health and
      obesity: metabolically healthy non-obese (MHNO), metabolically healthy obese
      (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy
      obese (MUHO). RESULTS: Mean values of CACS in the four groups were significantly
      different, except those between MHNO and MHO and between MUHNO and MUHO. When
      multinomial logistic regression analysis was performed with five CACS categories
      as the dependent variables and after adjusting for age, sex, and smoking status,
      the MHO, MUHNO, and MUHO groups showed significantly increased odds ratio for
      increasing CACS categories compared with no calcification status (5.221 for CACS
      >400 in MUHO group with 95% CI 2.856~5.032 with MHNO group as the reference).
      When other variables including the metabolic parameters were included in the same
      model, the risks were attenuated. CONCLUSION: Metabolic health is more closely
      associated with subclinical atherosclerosis than obesity as assessed by CACS.

PMID- 24040287
TI  - Myocarditis, disseminated infection, and early viral persistence following
      experimental coxsackievirus B infection of cynomolgus monkeys.
AB  - Coxsackievirus B (CVB) infection is a common cause of acute viral myocarditis.
      The clinical presentation of myocarditis caused by this enterovirus is highly
      variable, ranging from mildly symptoms to complete hemodynamic collapse. These
      variations in initial symptoms and in the immediate and long term outcomes of
      this disease have impeded development of effective treatment strategies. Nine
      cynomolgus monkeys were inoculated with myocarditic strains of CVB. Virological
      studies performed up to 28 days post-inoculation demonstrated the development of
      neutralizing antibody in all animals, and the presence of CVB in plasma. High
      dose intravenous inoculation (n = 2) resulted in severe disseminated disease,
      while low dose intravenous (n = 6) or oral infection (1 animal) resulted in
      clinically unapparent infection. Transient, minor, echocardiographic
      abnormalities were noted in several animals, but no animals displayed signs of
      significant acute cardiac failure. Although viremia rapidly resolved, signs of
      myocardial inflammation and injury were observed in all animals at the time of
      necropsy, and CVB was detected in postmortem myocardial specimens up to 28 days
      PI. This non-human primate system replicates many features of illness in acute
      coxsackievirus myocarditis and demonstrates that myocardial involvement may be
      common in enteroviral infection; it may provide a model system for testing of
      treatment strategies for enteroviral infections and acute coxsackievirus
      myocarditis.

PMID- 24040288
TI  - Fate of pup inside the Mycobacterium proteasome studied by in-cell NMR.
AB  - The Mycobacterium tuberculosis proteasome is required for maximum virulence and
      to resist killing by the host immune system. The prokaryotic ubiquitin-like
      protein, Pup-GGE, targets proteins for proteasome-mediated degradation. We
      demonstrate that Pup-GGQ, a precursor of Pup-GGE, is not a substrate for
      proteasomal degradation. Using STINT-NMR, an in-cell NMR technique, we studied
      the interactions between Pup-GGQ, mycobacterial proteasomal ATPase, Mpa, and Mtb
      proteasome core particle (CP) inside a living cell at amino acid residue
      resolution. We showed that under in-cell conditions, in the absence of the
      proteasome CP, Pup-GGQ interacts with Mpa only weakly, primarily through its C
      terminal region. When Mpa and non-stoichiometric amounts of proteasome CP are
      present, both the N-terminal and C-terminal regions of Pup-GGQ bind strongly to
      Mpa. This suggests a mechanism by which transient binding of Mpa to the
      proteasome CP controls the fate of Pup. 

PMID- 24040289
TI  - Describing temperament in an ungulate: a multidimensional approach.
AB  - Studies on animal temperament have often described temperament using a one
      dimensional scale, whereas theoretical framework has recently suggested two or
      more dimensions using terms like "valence" or "arousal" to describe these
      dimensions. Yet, the valence or assessment of a situation is highly individual.
      The aim of this study was to provide support for the multidimensional framework
      with experimental data originating from an economically important species (Bos
      taurus). We tested 361 calves at 90 days post natum (dpn) in a novel-object test.
      Using a principal component analysis (PCA), we condensed numerous behaviours into
      fewer variables to describe temperament and correlated these variables with
      simultaneously measured heart rate variability (HRV) data. The PCA resulted in
      two behavioural dimensions (principal components, PC): novel-object-related (PC
      1) and exploration-activity-related (PC 2). These PCs explained 58% of the
      variability in our data. The animals were distributed evenly within the two
      behavioural dimensions independent of their sex. Calves with different scores in
      these PCs differed significantly in HRV, and thus in the autonomous nervous
      system's activity. Based on these combined behavioural and physiological data we
      described four distinct temperament types resulting from two behavioural
      dimensions: "neophobic/fearful--alert", "interested--stressed",
      "subdued/uninterested--calm", and "neoophilic/outgoing--alert". Additionally, 38
      calves were tested at 90 and 197 dpn. Using the same PCA-model, they correlated
      significantly in PC 1 and tended to correlate in PC 2 between the two test ages.
      Of these calves, 42% expressed a similar behaviour pattern in both dimensions and
      47% in one. No differences in temperament scores were found between sexes or
      breeds. In conclusion, we described distinct temperament types in calves based on
      behavioural and physiological measures emphasising the benefits of a
      multidimensional approach.

PMID- 24040290
TI  - Stepwise assembly of fibrinogen is assisted by the endoplasmic reticulum lectin
      chaperone system in HepG2 cells.
AB  - The endoplasmic reticulum (ER) plays essential roles in protein folding and
      assembly of secretory proteins. ER-resident molecular chaperones and related
      enzymes assist in protein maturation by co-operated interactions and
      modifications. However, the folding/assembly of multimeric proteins is not well
      understood. Here, we show that the maturation of fibrinogen, a hexameric
      secretory protein (two trimers from alpha, beta and gamma subunits), occurs in a
      stepwise manner. The alphagamma complex, a precursor for the trimer, is retained
      in the ER by lectin-like chaperones, and the beta subunit is incorporated into
      the alphagamma complex immediately after translation. ERp57, a protein disulfide
      isomerase homologue, is involved in the hexamer formation from two trimers. Our
      results indicate that the fibrinogen hexamer is formed sequentially, rather than
      simultaneously, using kinetic pause by lectin chaperones. This study provides a
      novel insight into the assembly of most abundant multi-subunit secretory
      proteins. 

PMID- 24040291
TI  - Recruitment and resilience of a harvested Caribbean octocoral.
AB  - Disturbance events are an important component of the ecology of coral reefs and
      increasingly frequent disturbances coupled with a lack of population resilience
      may contribute to changes in the structure of coral reef communities. The harvest
      of the Caribbean octocoral Antillogorgia elisabethae provides an opportunity to
      explore the relationship between adult abundance and recruitment and the manner
      in which recruitment contributes to the resilience of local populations.
      Recruitment of A. elisabethae was monitored in 20, 1-m(2) quadrats at 8 sites
      along the southern edge of the Little Bahama Bank from 2004 through 2007. A.
      elisabethae has been harvested in The Bahamas for over fifteen years and all of
      the sites had been harvested three times, including a harvest during the course
      of the study. Abundances of adult colonies at those sites as well as a location
      that had not been harvested were also determined. Recruitment was highly
      variable, differing between sites, transects within sites, and, depending on the
      site, between years. Recruitment was best correlated with adult abundance
      averaged across the surrounding site. Regression analyses suggest abundance on
      smaller scales had only small effects on recruitment. The effects of the
      harvesting were site specific ranging from a 38 to 67% reduction in the density
      of mature colonies. The sites with the most abundant A. elisabethae continued to
      have the highest abundances after harvesting and there was no significant
      difference in recruitment before and after harvesting. Population size-structure
      at 6 of 8 sites that have been harvested multiple times exhibited an overall
      depletion in small colonies suggesting long term suppression of recruitment and
      declining populations. Severe depression of adult abundances coupled with local
      recruitment can create a negative feedback and lead to the decline of local
      populations. Populations that are dependent on self-recruitment are not resilient
      to large disturbance events. 

PMID- 24040292
TI  - Genetic background and climatic droplet keratopathy incidence in a Mapuche
      population from Argentina.
AB  - PURPOSE: To determine whether the incidence of and susceptibility to climatic
      droplet keratopathy (CDK), an acquired, often bilateral degenerative corneal
      disease, is influenced by the genetic background of the individuals who exhibit
      the disorder. METHODS: To determine whether the disease expression was influenced
      by the genetic ancestry of CDK cases in native Mapuche of the northwest area of
      Patagonia in Argentina, we examined mitochondrial DNA and Y-chromosome variation
      in 53 unrelated individuals. Twenty-nine of them were part of the CDK (patient)
      population, while 24 were part of the control group. The analysis revealed the
      maternal and paternal lineages that were present in the two study groups.
      RESULTS: This analysis demonstrated that nearly all persons had a Native American
      mtDNA background, whereas 50% of the CDK group and 37% of the control group had
      Native American paternal ancestry, respectively. There was no significant
      difference in the frequencies of mtDNA haplogroups between the CDK patient and
      control groups. Although the Y-chromosome data revealed differences in specific
      haplogroup frequencies between these two groups, there was no statistically
      significant relationship between individual paternal genetic backgrounds and the
      incidence or stage of disease. CONCLUSIONS: These results indicate a lack of
      correlation between genetic ancestry as represented by haploid genetic systems
      and the incidence of CDK in Mapuche populations. In addition, the mtDNA appears
      to play less of a role in CDK expression than for other complex diseases linked
      to bioenergetic processes. However, further analysis of the mtDNA genome sequence
      and other genes involved in corneal function may reveal the more precise role
      that mitochondria play in the expression of CDK.

PMID- 24040293
TI  - Lines of evidence-incremental markings in molar enamel of Soay sheep as revealed
      by a fluorochrome labeling and backscattered electron imaging study.
AB  - We studied the structural characteristics and periodicities of regular
      incremental markings in sheep enamel using fluorochrome injections for vital
      labeling of forming enamel and backscattered electron imaging in the scanning
      electron microscope. Microscopic analysis of mandibular first molars revealed the
      presence of incremental markings with a daily periodicity (laminations) that
      indicated successive positions of the forming front of interprismatic enamel. In
      addition to the laminations, incremental markings with a sub-daily periodicity
      were discernible both in interprismatic enamel and in enamel prisms. Five sub
      daily increments were present between two consecutive laminations. Backscattered
      electron imaging revealed that each sub-daily growth increment consisted of a
      broader and more highly mineralized band and a narrower and less mineralized band
      (line). The sub-daily markings in the prisms of sheep enamel morphologically
      resembled the (daily) prisms cross striations seen in primate enamel. Incremental
      markings with a supra-daily periodicity were not observed in sheep enamel. Based
      on the periodicity of the incremental markings, maximum mean daily apposition
      rates of 17.0 um in buccal enamel and of 13.4 um in lingual enamel were recorded.
      Enamel extension rates were also high, with maximum means of 180 um/day and 217
      um/day in upper crown areas of buccal and lingual enamel, respectively. Values in
      more cervical crown portions were markedly lower. Our results are in accordance
      with previous findings in other ungulate species. Using the incremental markings
      present in primate enamel as a reference could result in a misinterpretation of
      the incremental markings in ungulate enamel. Thus, the sub-daily growth
      increments in the prisms of ungulate enamel might be mistaken as prism cross
      striations with a daily periodicity, and the laminations misidentified as striae
      of Retzius with a supra-daily periodicity. This would lead to a considerable
      overestimation of crown formation times in ungulate teeth. 

PMID- 24040294
TI  - Characterization of mRNA-cytoskeleton interactions in situ using FMTRIP and
      proximity ligation.
AB  - Many studies have demonstrated an association between the cytoskeleton and mRNA,
      as well as the asymmetric distribution of mRNA granules within the cell in
      response to various signaling events. It is likely that the extensive
      cytoskeletal network directs mRNA transport and localization, with different
      cytoskeletal elements having their own specific roles. In order to understand the
      spatiotemporal changes in the interactions between the mRNA and the cytoskeleton
      as a response to a stimulus, a technique that can visualize and quantify these
      changes across a population of cells while capturing cell-to-cell variations is
      required. Here, we demonstrate a method for imaging and quantifying mRNA
      cytoskeleton interactions on a per cell basis with single-interaction
      sensitivity. Using a proximity ligation assay with flag-tagged multiply-labeled
      tetravalent RNA imaging probes (FMTRIP), we quantified interactions between mRNAs
      and beta-tubulin, vimentin, or filamentous actin (F-actin) for two different
      mRNAs, poly(A) + and beta-actin mRNA, in two different cell types, A549 cells and
      human dermal fibroblasts (HDF). We found that the mRNAs interacted predominantly
      with F-actin (>50% in HDF, >20% in A549 cells), compared to beta-tubulin (<5%)
      and vimentin (11-13%). This likely reflects differences in mRNA management by the
      two cell types. We then quantified changes in these interactions in response to
      two perturbations, F-actin depolymerization and arsenite-induced oxidative
      stress, both of which alter either the cytoskeleton itself and mRNA localization.
      Both perturbations led to a decrease in poly(A) + mRNA interactions with F-actin
      and an increase in the interactions with microtubules, in a time dependent
      manner. 

PMID- 24040295
TI  - Impact of marker ascertainment bias on genomic selection accuracy and estimates
      of genetic diversity.
AB  - Genome-wide molecular markers are often being used to evaluate genetic diversity
      in germplasm collections and for making genomic selections in breeding programs.
      To accurately predict phenotypes and assay genetic diversity, molecular markers
      should assay a representative sample of the polymorphisms in the population under
      study. Ascertainment bias arises when marker data is not obtained from a random
      sample of the polymorphisms in the population of interest. Genotyping-by
      sequencing (GBS) is rapidly emerging as a low-cost genotyping platform, even for
      the large, complex, and polyploid wheat (Triticum aestivum L.) genome. With GBS,
      marker discovery and genotyping occur simultaneously, resulting in minimal
      ascertainment bias. The previous platform of choice for whole-genome genotyping
      in many species such as wheat was DArT (Diversity Array Technology) and has
      formed the basis of most of our knowledge about cereals genetic diversity. This
      study compared GBS and DArT marker platforms for measuring genetic diversity and
      genomic selection (GS) accuracy in elite U.S. soft winter wheat. From a set of
      365 breeding lines, 38,412 single nucleotide polymorphism GBS markers were
      discovered and genotyped. The GBS SNPs gave a higher GS accuracy than 1,544 DArT
      markers on the same lines, despite 43.9% missing data. Using a bootstrap
      approach, we observed significantly more clustering of markers and ascertainment
      bias with DArT relative to GBS. The minor allele frequency distribution of GBS
      markers had a deficit of rare variants compared to DArT markers. Despite the
      ascertainment bias of the DArT markers, GS accuracy for three traits out of four
      was not significantly different when an equal number of markers were used for
      each platform. This suggests that the gain in accuracy observed using GBS
      compared to DArT markers was mainly due to a large increase in the number of
      markers available for the analysis. 

PMID- 24040296
TI  - Temperatures in excess of critical thresholds threaten nestling growth and
      survival in a rapidly-warming arid savanna: a study of common fiscals.
AB  - Frequency, duration, and intensity of hot-weather events are all predicted to
      increase with climate warming. Despite this, mechanisms by which temperature
      increases affect individual fitness and drive population-level changes are poorly
      understood. We investigated the link between daily maximum air temperature (tmax)
      and breeding success of Kalahari common fiscals (Lanius collaris) in terms of the
      daily effect on nestling body-mass gain, and the cumulative effect on size and
      age of fledglings. High tmax reduced mass gain of younger, but not older
      nestlings and average nestling-period tmax did not affect fledgling size.
      Instead, the frequency with which tmax exceeded critical thresholds (tcrits)
      significantly reduced fledging body mass (tcrit = 33 degrees C) and tarsus length
      (tcrit= 37 degrees C), as well as delaying fledging (tcrit= 35 degrees C). Nest
      failure risk was 4.2% per day therefore delays reduced fledging probability.
      Smaller size at fledging often correlates with reduced lifetime fitness and might
      also underlie documented adult body-size reductions in desert birds in relation
      to climate warming. Temperature thresholds above which organisms incur fitness
      costs are probably common, as physiological responses to temperature are non
      linear. Understanding the shape of the relationship between temperature and
      fitness has implications for our ability to predict species' responses to climate
      change.

PMID- 24040297
TI  - Cag type IV secretion system: CagI independent bacterial surface localization of
      CagA.
AB  - Helicobacter pylori Cag type IV secretion system (Cag-T4SS) is a multi-component
      transporter of oncoprotein CagA across the bacterial membranes into the host
      epithelial cells. To understand the role of unique Cag-T4SS component CagI in
      CagA translocation, we have characterized it by biochemical and microscopic
      approaches. We observed that CagI is a predominantly membrane attached
      periplasmic protein partially exposed to the bacterial surface especially on the
      pili. The association of the protein with membrane appeared to be loose as it
      could be easily recovered in soluble fraction. We documented that the stability
      of the protein is dependent on several key components of the secretion system and
      it has multiple interacting partners including a non-cag-PAI protein HP1489.
      Translocation of CagA across the bacterial membranes to cell surface is CagI
      independent process. The observations made herein are expected to assist in
      providing an insight into the substrate translocation by the Cag-T4SS system and
      Helicobacter pylori pathogenesis. 

PMID- 24040298
TI  - Inhibition of lipolysis by mercaptoacetate and etomoxir specifically sensitize
      drug-resistant lung adenocarcinoma cell to paclitaxel.
AB  - Chemoresistance is a major cause of treatment failure in patients with lung
      cancer. Although the extensive efforts have been made in overcoming
      chemoresistance, the underlying mechanisms are still elusive. Cancer cells
      reprogram cellular metabolism to satisfy the demands of malignant phenotype. To
      reveal roles of cancer metabolism in regulating chemoresistance, we profiled the
      metabolic characteristics in paclitaxel-resistant lung cancer cells by flux
      assay. Glucose and oleate metabolism were significantly different between
      resistant and non-resistant cells. In addition, targeting metabolism as a
      strategy to overcome drug resistance was investigated using specific metabolic
      inhibitors. Inhibition of glycolysis and oxidative phosphorylation by 2
      deoxyglucose and malonate, respectively, potentiated the effects of paclitaxel on
      nonresistant lung adenocarcinoma cells but not paclitaxel-resistant cells. By
      contrast, inhibition of lipolysis by mercaptoacetate or etomoxir synergistically
      inhibited drug-resistant lung adenocarcinoma cell proliferation. We conclude that
      lipolysis inhibition potentially be a therapeutic strategy to overcome drug
      resistance in lung cancer. 

PMID- 24040299
TI  - Opsonising antibodies to P. falciparum merozoites associated with immunity to
      clinical malaria.
AB  - Naturally acquired humoral immunity to the malarial parasite Plasmodium
      falciparum can protect against disease, although the precise mechanisms remain
      unclear. Although antibody levels can be measured by ELISA, few studies have
      investigated functional antibody assays in relation to clinical outcomes. In this
      study we applied a recently developed functional assay of antibody-mediated
      opsonisation of merozoites, to plasma samples from a longitudinal cohort study
      conducted in a malaria endemic region of Papua New Guinea (PNG). Phagocytic
      activity was quantified by flow cytometry using a standardized and high
      throughput protocol, and was subsequently evaluated for association with
      protection from clinical malaria and high-density parasitemia. Opsonising
      antibody responses were found to: i) increase with age, ii) be enhanced by
      concurrent infection, and iii) correlate with protection from clinical episodes
      and high-density parasitemia. Stronger protective associations were observed in
      individuals with no detectable parasitemia at baseline. This study presents the
      first evidence for merozoite phagocytosis as a correlate of acquired immunity and
      clinical protection against P. falciparum malaria. 

PMID- 24040300
TI  - In vitro screening for compounds that enhance human L1 mobilization.
AB  - The Long interspersed element 1 (LINE1 or L1) retrotransposon constitutes 17% of
      the human genome. There are currently 80-100 human L1 elements that are thought
      to be active in any diploid human genome. These elements can mobilize into new
      locations of the genome, resulting in changes in genomic information. Active L1s
      are thus considered to be a type of endogenous mutagen, and L1 insertions can
      cause disease. Certain stresses, such as gamma radiation, oxidative stress, and
      treatment with some agents, can induce transcription and/or mobilization of
      retrotransposons. In this study, we used a reporter gene assay in HepG2 cells to
      screen compounds for the potential to enhance the transcription of human L1. We
      assessed 95 compounds including genotoxic agents, substances that induce cellular
      stress, and commercially available drugs. Treatment with 15 compounds increased
      the L1 promoter activity by >1.5-fold (p<0.05) after 6 or 24 hours of treatment.
      In particular, genotoxic agents (benzo[a]pyrene, camptothecin, cytochalasin D,
      merbarone, and vinblastine), PPARalpha agonists (bezafibrate and fenofibrate),
      and non-steroidal anti-inflammatory drugs (diflunisal, flufenamic acid,
      salicylamide, and sulindac) induced L1 promoter activity. To examine their
      effects on L1 retrotransposition, we developed a high-throughput real-time
      retrotransposition assay using a novel secreted Gaussia luciferase reporter
      cassette. Three compounds (etomoxir, WY-14643, and salicylamide) produced a
      significant enhancement in L1 retrotransposition. This is the first study to
      report the effects of a wide variety of compounds on L1 transcription and
      retrotransposition. These results suggest that certain chemical- and drug-induced
      stresses might have the potential to cause genomic mutations by inducing L1
      mobilization. Thus, the risk of induced L1 transcription and retrotransposition
      should be considered during drug safety evaluation and environmental risk
      assessments of chemicals. 

PMID- 24040301
TI  - Magnetic resonance spectroscopic imaging and volumetric measurements of the brain
      in patients with postcancer fatigue: a randomized controlled trial.
AB  - BACKGROUND: Postcancer fatigue is a frequently occurring problem, impairing
      quality of life. Until now, little is known about (neuro) physiological factors
      determining postcancer fatigue. For non-cancer patients with chronic fatigue
      syndrome, certain characteristics of brain morphology and metabolism have been
      identified in previous studies. We investigated whether these volumetric and
      metabolic traits are a reflection of fatigue in general and thus also of
      importance for postcancer fatigue. METHODS: Fatigued patients were randomly
      assigned to either the intervention condition (cognitive behavior therapy) or the
      waiting list condition. Twenty-five patients in the intervention condition and
      fourteen patients in the waiting list condition were assessed twice, at baseline
      and six months later. Baseline measurements of 20 fatigued patients were compared
      with 20 matched non-fatigued controls. All participants had completed treatment
      of a malignant, solid tumor minimal one year earlier. Global brain volumes,
      subcortical brain volumes, metabolite tissue concentrations, and metabolite
      ratios were primary outcome measures. RESULTS: Volumetric and metabolic
      parameters were not significantly different between fatigued and non-fatigued
      patients. Change scores of volumetric and metabolic parameters from baseline to
      follow-up were not significantly different between patients in the therapy and
      the waiting list group. Patients in the therapy group reported a significant
      larger decrease in fatigue scores than patients in the waiting list group.
      CONCLUSIONS: No relation was found between postcancer fatigue and the studied
      volumetric and metabolic markers. This may suggest that, although postcancer
      fatigue and chronic fatigue syndrome show strong resemblances as a clinical
      syndrome, the underlying physiology is different. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT01096641.

PMID- 24040302
TI  - Myc-dependent genome instability and lifespan in Drosophila.
AB  - The Myc family of transcription factors are key regulators of cell growth and
      proliferation that are dysregulated in a large number of human cancers. When
      overexpressed, Myc family proteins also cause genomic instability, a hallmark of
      both transformed and aging cells. Using an in vivo lacZ mutation reporter, we
      show that overexpression of Myc in Drosophila increases the frequency of large
      genome rearrangements associated with erroneous repair of DNA double-strand
      breaks (DSBs). In addition, we find that overexpression of Myc shortens adult
      lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and
      extends lifespan. Our data provide the first evidence that Myc may act as a pro
      aging factor, possibly through its ability to greatly increase genome
      instability. 

PMID- 24040303
TI  - Microarray analyses and comparisons of upper or lower flanks of rice shoot base
      preceding gravitropic bending.
AB  - Gravitropism is a complex process involving a series of physiological pathways.
      Despite ongoing research, gravitropism sensing and response mechanisms are not
      well understood. To identify the key transcripts and corresponding pathways in
      gravitropism, a whole-genome microarray approach was used to analyze transcript
      abundance in the shoot base of rice (Oryza sativa sp. japonica) at 0.5 h and 6 h
      after gravistimulation by horizontal reorientation. Between upper and lower
      flanks of the shoot base, 167 transcripts at 0.5 h and 1202 transcripts at 6 h
      were discovered to be significantly different in abundance by 2-fold. Among these
      transcripts, 48 were found to be changed both at 0.5 h and 6 h, while 119
      transcripts were only changed at 0.5 h and 1154 transcripts were changed at 6 h
      in association with gravitropism. MapMan and PageMan analyses were used to
      identify transcripts significantly changed in abundance. The asymmetric
      regulation of transcripts related to phytohormones, signaling, RNA transcription,
      metabolism and cell wall-related categories between upper and lower flanks were
      demonstrated. Potential roles of the identified transcripts in gravitropism are
      discussed. Our results suggest that the induction of asymmetrical transcription,
      likely as a consequence of gravitropic reorientation, precedes gravitropic
      bending in the rice shoot base. 

PMID- 24040304
TI  - An initial psychometric evaluation and exploratory cross-sectional study of the
      body checking questionnaire among Brazilian women.
AB  - Body checking is considered an expression of an excessive preoccupation with
      appearance. The first aim of this study was to evaluate the psychometric
      properties of a Brazilian Portuguese version of the Body Checking Questionnaire
      (BCQ). Additionally, we wanted to examine the questionnaire's associations with
      body avoidance behaviour, body mass index, dietary habits, and the intensity,
      frequency, and length of physical exercise. Finally, we also examined the
      differences between the total BCQ score and the individual BCQ factor scores.
      Differences between active and sedentary persons and between non-dieters and
      those on weight-loss diets were also analyzed. For the psychometric study, 546
      female public university students from four different courses were surveyed. Two
      minor samples of university students and eating disorders women were also
      recruited. In the second part of the study, 403 women were recruited from weight
      loss programs, gyms, and a university. All participants were verbally invited to
      participate in the research and voluntarily took part. Confirmatory factor
      analysis showed a good fit to the original model of the Brazilian BCQ that
      retained all 23 items. Satisfactory evidence of construct validity and internal
      consistency were also generated through analysis of factor loadings, t-values,
      Cronbach's alpha, and construct reliability tests. The results also showed
      associations among body checking and body avoidance, body satisfaction, social
      anxiety, body mass index, and the frequency and intensity of physical exercise.
      Significant differences were found between non-dieters and weight-loss dieters
      for all BCQ factors and the total BCQ score. For physically active and sedentary
      persons, a significant difference was only observed for idiosyncratic checking
      behaviour. In conclusion, the BCQ appears to be a valid and reliable scale for
      Brazilian research, and the associations and differences found in this study
      suggest that women at gyms and especially in weight-loss programs should be
      targeted for future body checking studies. 

PMID- 24040305
TI  - Inorganic polyphosphate suppresses lipopolysaccharide-induced inducible nitric
      oxide synthase (iNOS) expression in macrophages.
AB  - In response to infection, macrophages produce a series of inflammatory mediators,
      including nitric oxide (NO), to eliminate pathogens. The production of these
      molecules is tightly regulated via various mechanisms, as excessive responses are
      often detrimental to host tissues. Here, we report that inorganic polyphosphate
      [poly(P)], a linear polymer of orthophosphate ubiquitously found in mammalian
      cells, suppresses inducible nitric oxide synthase (iNOS) expression induced by
      lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, in
      mouse peritoneal macrophages. Poly(P) with longer chains is more potent than
      those with shorter chains in suppressing LPS-induced iNOS expression. In
      addition, poly(P) decreased LPS-induced NO release. Moreover, poly(P) suppressed
      iNOS mRNA expression induced by LPS stimulation, thereby indicating that poly(P)
      reduces LPS-induced iNOS expression by down-regulation at the mRNA level. In
      contrast, poly(P) did not affect the LPS-induced release of TNF, another
      inflammatory mediator. Poly(P) may serve as a regulatory factor of innate
      immunity by modulating iNOS expression in macrophages. 

PMID- 24040306
TI  - Angiogenesis and lymphangiogenesis in the spectrum of leprosy and its reactional
      forms.
AB  - BACKGROUND: Angiogenesis and lymphangiogenesis are the processes of
      neovascularization that evolve from preexisting blood and lymphatic vessels.
      There are few studies on angiogenesis and none on lymphangiogenesis in leprosy.
      Thus, the role of neovascularization in the pathophysiological mechanisms of the
      disease was studied across the spectrum of leprosy, its reactional states and its
      residual lesions. METHODOLOGY/PRINCIPAL FINDINGS: Seventy-six biopsies of leprosy
      skin lesions and seven healthy controls were selected. Fifty-five serum samples
      were used for the detection of CD105 by ELISA. Histological sections were stained
      with antibodies against CD31 (blood and lymphatic vessels), D2-40/podoplanin
      (lymphatic vessels), and CD105/endoglin (neovessels). Microvessels were counted
      in 100 high-power fields (400x) and the number of vessels was evaluated in
      relation to the extension of the inflammatory infiltrate (0-3), to the bacillary
      index (0-6) and to the clinical forms. Angiogenesis, as marked by CD31 and CD105,
      was observed across the leprosy spectrum, compared with the controls.
      Additionally, there was a positive correlation between these markers with
      extension of the infiltrate (p <0.0001). For D2/40, lymphangiogenesis was
      observed in the tuberculoid form (p <0.0001). There was no statistical
      significance for values of CD105 detected in plasma by ELISA.
      CONCLUSIONS/SIGNIFICANCE: Angiogenesis is present across the spectrum of leprosy
      and in its reactional forms. The increase in the number of vessels, as detected
      by CD31 and CD105 staining, is related to the extension of the inflammatory
      infiltrate. Samples from reactional lesions have a higher number of CD31+ and
      CD105+ stained vessels, which indicates their involvement in the
      pathophysiological mechanisms of the reactional states. The regression of lesions
      is accompanied by the regression of neovascularization. Drugs inhibiting
      angiogenesis may be relevant in the treatment of leprosy, in addition to
      multidrugtherapy, and in the prevention of the development of reactions.

PMID- 24040307
TI  - Pim-1 kinase phosphorylates and stabilizes 130 kDa FLT3 and promotes aberrant
      STAT5 signaling in acute myeloid leukemia with FLT3 internal tandem duplication.
AB  - The type III receptor tyrosine kinase fms-like tyrosine kinase 3 (FLT3) is
      expressed on both normal hematopoietic stem cells and acute myeloid leukemia
      (AML) cells and regulates their proliferation. Internal tandem duplication (ITD)
      mutation of FLT3 is present in a third of AML cases, results in constitutive
      activation and aberrant signaling of FLT3, and is associated with adverse
      treatment outcomes. While wild-type (WT) FLT3 is predominantly a 150 kDa complex
      glycosylated cell surface protein, FLT3-ITD is partially retained in the
      endoplasmic reticulum as a 130 kDa underglycosylated species associated with the
      chaperones calnexin and heat shock protein (HSP) 90, and mediates aberrant STAT5
      signaling, which upregulates the oncogenic serine/threonine kinase Pim-1. FLT3
      contains a Pim-1 substrate consensus serine phosphorylation site, and we
      hypothesized that it might be a Pim-1 substrate. Pim-1 was indeed found to
      directly interact with and serine-phosphorylate FLT3. Pim-1 inhibition decreased
      the expression and half-life of 130 kDa FLT3, with partial abrogation by
      proteasome inhibition, in association with decreased FLT3 binding to calnexin and
      HSP90, and increased 150 kDa FLT3 expression and half-life, with abrogation by
      inhibition of glycosylation. These findings were consistent with Pim-1
      stabilizing FLT3-ITD as a 130 kDa species associated with calnexin and HSP90 and
      inhibiting its glycosylation to form the 150 kDa species. Pim-1 knockdown effects
      were similar. Pim-1 inhibition also decreased phosphorylation of FLT3 at tyrosine
      591 and of STAT5, and expression of Pim-1 itself, consistent with inhibition of
      the FLT3-ITD-STAT5 signaling pathway. Finally, Pim-1 inhibition synergized with
      FLT3 inhibition in inducing apoptosis of FLT3-ITD cells. This is, to our
      knowledge, the first demonstration of a role of Pim-1 in a positive feedback loop
      promoting aberrant signaling in malignant cells. 

PMID- 24040308
TI  - Tumor and endothelial cell-derived microvesicles carry distinct CEACAMs and
      influence T-cell behavior.
AB  - Normal and malignant cells release a variety of different vesicles into their
      extracellular environment. The most prominent vesicles are the microvesicles
      (MVs, 100-1000 nm in diameter), which are shed of the plasma membrane, and the
      exosomes (70-120 nm in diameter), derivates of the endosomal system. MVs have
      been associated with intercellular communication processes and transport numerous
      proteins, lipids and RNAs. As essential component of immune-escape mechanisms
      tumor-derived MVs suppress immune responses. Additionally, tumor-derived MVs have
      been found to promote metastasis, tumor-stroma interactions and angiogenesis.
      Since members of the carcinoembryonic antigen related cell adhesion molecule
      (CEACAM)-family have been associated with similar processes, we studied the
      distribution and function of CEACAMs in MV fractions of different human
      epithelial tumor cells and of human and murine endothelial cells. Here we
      demonstrate that in association to their cell surface phenotype, MVs released
      from different human epithelial tumor cells contain CEACAM1, CEACAM5 and CEACAM6,
      while human and murine endothelial cells were positive for CEACAM1 only.
      Furthermore, MVs derived from CEACAM1 transfected CHO cells carried CEACAM1. In
      terms of their secretion kinetics, we show that MVs are permanently released in
      low doses, which are extensively increased upon cellular starvation stress.
      Although CEACAM1 did not transmit signals into MVs it served as ligand for CEACAM
      expressing cell types. We gained evidence that CEACAM1-positive MVs significantly
      increase the CD3 and CD3/CD28-induced T-cell proliferation. All together, our
      data demonstrate that MV-bound forms of CEACAMs play important roles in
      intercellular communication processes, which can modulate immune response, tumor
      progression, metastasis and angiogenesis.

PMID- 24040309
TI  - Neural correlates of psychotherapy in anxiety and depression: a meta-analysis.
AB  - Several studies have used neuroimaging methods to identify neural change in brain
      networks associated to emotion regulation after psychotherapy of depression and
      anxiety. In the present work we adopted a meta-analytic technique specific to
      neuroimaging data to evaluate the consistence of empirical findings and assess
      models of therapy that have been proposed in the literature. Meta-analyses were
      conducted with the Activation Likelihood Estimation technique, which evaluates
      the overlap between foci of activation across studies. The analysis included 16
      studies found in Pubmed (200 foci of activation and 193 patients). Separate meta
      analyses were conducted on studies of 1) depression, post-traumatic stress
      disorder and panic disorder investigated with rest state metabolism (6 studies,
      70 patients); 2) depression, post-traumatic stress disorder and panic disorder
      investigated with task-related activation studies (5 studies, 65 patients); 3)
      the previous studies considered jointly; and 4) phobias investigated with studies
      on exposure-related activation (5 studies, 57 patients). Studies on anxiety and
      depression gave partially consistent results for changes in the dorsomedial
      prefrontal cortex and in the posterior cingulated gyrus/precuneus. Several areas
      of change in the temporal lobes were also observed. Studies on the therapy of
      phobia were consistent with a reduction of activity in medial temporal areas. The
      cluster of change in the prefrontal cortex may refer to increased recruitment of
      control processes, as hypothesized by influential models of emotion regulation
      changes due to psychotherapy. However, not all areas associated with controlled
      emotion regulation were detected in the meta-analysis, while involvement of
      midline structures suggested changes in self-related information processing.
      Changes in phobia were consistent with reduced reactivity to phobic stimuli. 

PMID- 24040310
TI  - Integrin-specific control of focal adhesion kinase and RhoA regulates membrane
      protrusion and invasion.
AB  - Cell invasion through extracellular matrix (ECM) is a hallmark of the metastatic
      cascade. Cancer cells require adhesion to surrounding tissues for efficient
      migration to occur, which is mediated through the integrin family of receptors.
      Alterations in expression levels of beta1 and beta3 integrins have previously
      been reported in a number of human cancers. However, whether there are specific
      roles for these ubiquitous receptors in mediating cell invasion remains unclear.
      Here we demonstrate that loss of beta1 but not beta3 integrins leads to increased
      spread cell area and focal adhesion number in cells on 2D immobilized
      fibronectin. Increased adhesion numbers in beta1 knockdown cells correlated with
      decreased cell migration on 2D surfaces. Conversely, cells depleted of beta1
      integrins showed increased migration speed on 3D cell-derived matrix as well as
      in 3D organotypic cultures and inverted invasion assays. This increased invasive
      potential was also seen in cells lacking beta3 integrin but only in 3D cultures
      containing fibroblasts. Mechanistically, in situ analysis using FRET biosensors
      revealed that enhanced invasion in cells lacking beta1 integrins was directly
      coupled with reduced activation of focal adhesion kinase (FAK) and the small
      GTPase RhoA resulting in formation of enhanced dynamic protrusions and increased
      invasion. These reductions in FAK-RhoA signal activation were not detected in
      beta3 knockdown cells under the same conditions. This data demonstrates a
      specific role for beta1 integrins in the modulation of a FAK-RhoA-actomyosin
      signaling axis to regulate cell invasion through complex ECM environments.

PMID- 24040312
TI  - Does sex matter? Temporal and spatial patterns of cougar-human conflict in
      British Columbia.
AB  - Wildlife-human conflicts occur wherever large carnivores overlap human inhabited
      areas. Conflict mitigation can be facilitated by understanding long-term dynamics
      and examining sex-structured conflict patterns. Predicting areas with high
      probability of conflict helps focus management strategies in order to proactively
      decrease carnivore mortality. We investigated the importance of cougar (Puma
      concolor) habitat, human landscape characteristics and the combination of habitat
      and human features on the temporal and spatial patterns of cougar-human conflicts
      in British Columbia. Conflicts (n = 1,727; 1978-2007) involved similar numbers of
      male and female cougars with conflict rate decreasing over the past decade.
      Conflicts were concentrated within the southern part of the province with the
      most conflicts per unit area occurring on Vancouver Island. For both sexes, the
      most supported spatial models for the most recent (1998-2007) conflicts contained
      both human and habitat variables. Conflicts were more likely to occur close to
      roads, at intermediate elevations and far from the northern edge of the cougar
      distribution range in British Columbia. Male cougar conflicts were more likely to
      occur in areas of intermediate human density. Unlike cougar conflicts in other
      regions, cattle density was not a significant predictor of conflict location.
      With human populations expanding, conflicts are expected to increase.
      Conservation tools, such as the maps predicting conflict hotspots from this
      study, can help focus management efforts to decrease carnivore-human conflict. 

PMID- 24040311
TI  - Comprehensive analysis of LANA interacting proteins essential for viral genome
      tethering and persistence.
AB  - Kaposi's sarcoma associated herpesvirus is tightly linked to multiple human
      malignancies including Kaposi's sarcoma (KS), Primary Effusion Lymphoma (PEL) and
      Multicentric Castleman's Disease (MCD). KSHV like other herpesviruses establishes
      life-long latency in the infected host by persisting as chromatin and tethering
      to host chromatin through the virally encoded protein Latency Associated Nuclear
      Antigen (LANA). LANA, a multifunctional protein, is capable of binding to a large
      number of cellular proteins responsible for transcriptional regulation of various
      cellular and viral pathways involved in blocking cell death and promoting cell
      proliferation. This leads to enhanced cell division and replication of the viral
      genome, which segregates faithfully in the dividing tumor cells. The mechanism of
      genome segregation is well known and the binding of LANA to nucleosomal proteins,
      throughout the cell cycle, suggests that these interactions play an important
      role in efficient segregation. Various biochemical methods have identified a
      large number of LANA binding proteins, including histone H2A/H2B, histone H1,
      MeCP2, DEK, CENP-F, NuMA, Bub1, HP-1, and Brd4. These nucleosomal proteins may
      have various functions in tethering of the viral genome during specific phases of
      the viral life cycle. Therefore, we performed a comprehensive analysis of their
      interaction with LANA using a number of different assays. We show that LANA binds
      to core nucleosomal histones and also associates with other host chromatin
      proteins including histone H1 and high mobility group proteins (HMGs). We used
      various biochemical assays including co-immunoprecipitation and in-vivo
      localization by split GFP and fluorescence resonance energy transfer (FRET) to
      demonstrate their association. 

PMID- 24040313
TI  - Decoding of repeated objects from local field potentials in macaque inferior
      temporal cortex.
AB  - Stimulus repetition produces a decrease of the response and affects neuronal
      synchronization of macaque inferior temporal (IT) neurons. Previously we showed
      that such stimulus-specific adaptation results in a decreased accuracy by which
      IT neurons encode repeated compared to non-repeated objects. Not only spiking
      activity, but also local field potentials (LFPs) are affected by repetition. Here
      we ask how the repetition-induced changes in IT LFPs affect object decoding
      accuracy. To answer this, we recorded local field potentials using a laminar
      microelectrode in macaque IT. We presented two familiar stimuli each for 500 ms
      successively with an inter-stimulus interval of 500 ms. Trials consisted either
      of a repetition of the same stimulus or of their alternation. Machine learning
      based classifier was employed to decode stimulus identity from the LFP power in
      different frequency bands of each penetration. We found that the object
      classification accuracy depended strongly on spectral frequency, with frequencies
      below 30 Hz (alpha and beta) producing greater accuracies than gamma bands.
      However, the effect of repetition on classification accuracy was stronger at the
      gamma frequencies, showing a decrease in classification accuracy for repeated
      stimuli and a tendency for an improved object encoding when the stimulus was
      preceded by a different stimulus. The present results demonstrate that due to
      adapting input, stimulus encoding in IT (1) can be more accurate for stimuli that
      differ from recently preceding ones while being impaired for stimuli that are
      repeated, and (2) these effects are more pronounced at high spectral frequencies
      of the LFP. 

PMID- 24040314
TI  - Scaffold-based delivery of autologous mesenchymal stem cells for mandibular
      distraction osteogenesis: preliminary studies in a porcine model.
AB  - PURPOSE: Bone regeneration through distraction osteogenesis (DO) is promising but
      remarkably slow. To accelerate it, autologous mesenchymal stem cells have been
      directly injected to the distraction site in a few recent studies. Compared to
      direct injection, a scaffold-based method can provide earlier cell delivery with
      potentially better controlled cell distribution and retention. This pilot project
      investigated a scaffold-based cell-delivery approach in a porcine mandibular DO
      model. MATERIALS AND METHODS: Eleven adolescent domestic pigs were used for two
      major sets of studies. The in-vitro set established methodologies to: aspirate
      bone marrow from the tibia; isolate, characterize and expand bone marrow-derived
      mesenchymal stem cells (BM-MSCs); enhance BM-MSC osteogenic differentiation using
      FGF-2; and confirm cell integration with a gelatin-based Gelfoam scaffold. The in
      vivo set transplanted autologous stem cells into the mandibular distraction sites
      using Gelfoam scaffolds; completed a standard DO-course and assessed bone
      regeneration by macroscopic, radiographic and histological methods. Repeated
      measure ANOVAs and t-tests were used for statistical analyses. RESULTS: From
      aspirated bone marrow, multi-potent, heterogeneous BM-MSCs purified from
      hematopoietic stem cell contamination were obtained. FGF-2 significantly enhanced
      pig BM-MSC osteogenic differentiation and proliferation, with 5 ng/ml determined
      as the optimal dosage. Pig BM-MSCs integrated readily with Gelfoam and maintained
      viability and proliferative ability. After integration with Gelfoam scaffolds,
      2.4-5.8*10(7) autologous BM-MSCs (undifferentiated or differentiated) were
      transplanted to each experimental DO site. Among 8 evaluable DO sites included in
      the final analyses, the experimental DO sites demonstrated less interfragmentary
      mobility, more advanced gap obliteration, higher mineral content and faster
      mineral apposition than the control sites, and all transplanted scaffolds were
      completely degraded. CONCLUSION: It is technically feasible and biologically
      sound to deliver autologous BM-MSCs to the distraction site immediately after
      osteotomy using a Gelfoam scaffold to enhance mandibular DO.

PMID- 24040315
TI  - Over-expression of a tobacco nitrate reductase gene in wheat (Triticum aestivum
      L.) increases seed protein content and weight without augmenting nitrogen
      supplying.
AB  - Heavy nitrogen (N) application to gain higher yield of wheat (Triticum aestivum
      L.) resulted in increased production cost and environment pollution. How to
      diminish the N supply without losing yield and/or quality remains a challenge. To
      meet the challenge, we integrated and expressed a tobacco nitrate reductase gene
      (NR) in transgenic wheat. The 35S-NR gene was transferred into two winter
      cultivars, "Nongda146" and "Jimai6358", by Agrobacterium-mediation. Over
      expression of the transgene remarkably enhanced T1 foliar NR activity and
      significantly augmented T2 seed protein content and 1000-grain weight in 63.8%
      and 68.1% of T1 offspring (total 67 individuals analyzed), respectively. Our
      results suggest that constitutive expression of foreign nitrate reductase gene(s)
      in wheat might improve nitrogen use efficiency and thus make it possible to
      increase seed protein content and weight without augmenting N supplying. 

PMID- 24040316
TI  - Assembly of bio-nanoparticles for double controlled drug release.
AB  - A critical limiting factor of chemotherapy is the unacceptably high toxicity. The
      use of nanoparticle based drug carriers has significantly reduced the side
      effects and facilitated the delivery of drugs. Source of the remaining side
      effect includes (1) the broad final in vivo distribution of the administrated
      nanoparticles, and (2) strong basal drug release from nanoparticles before they
      could reach the tumor. Despite the advances in pH-triggered release, undesirable
      basal drug release has been a constant challenge under in vivo conditions. In
      this study, functionalized single walled carbon nanohorn supported
      immunoliposomes were assembled for paclitaxel delivery. The immunoliposomes were
      formulated with polyethylene glycol, thermal stable and pH sensitive
      phospholipids. Each nanohorn was found to be encapsulated within one
      immunoliposome. Results showed a highly pH dependent release of paclitaxel in the
      presence of serum at body temperature with minimal basal release under
      physiological conditions. Upon acidification, paclitaxel was released at a steady
      rate over 30 days with a cumulative release of 90% of the loaded drug. The drug
      release results proved our hypothesized double controlled release mechanism from
      the nanoparticles. Other results showed the nanoparticles have doubled loading
      capacity compared to that of traditional liposomes and higher affinity to breast
      cancer cells overexpressing Her2 receptors. Internalized nanoparticles were found
      in lysosomes. 

PMID- 24040317
TI  - Dietary restriction extends lifespan in wild-derived populations of Drosophila
      melanogaster.
AB  - Dietary restriction (DR) can result in lifespan-extension and improved function
      and health during ageing. Although the impact of DR on lifespan and health has
      been established in a variety of organisms, most DR experiments are carried out
      on laboratory strains that have often undergone adaptation to laboratory
      conditions. The effect of DR on animals recently derived from wild populations is
      rarely assessed. We measured the DR response of four populations of Drosophila
      melanogaster within two generations of collection from the wild. All populations
      responded to DR with an increase in lifespan and a decrease in female fecundity,
      similarly to a control, laboratory-adapted strain. These effects of DR are thus
      not a result of adaptation to laboratory conditions, and reflect the
      characteristics of natural populations. 

PMID- 24040318
TI  - Children's computation of complex linguistic forms: a study of frequency and
      imageability effects.
AB  - This study investigates the storage vs. composition of inflected forms in
      typically-developing children. Children aged 8-12 were tested on the production
      of regular and irregular past-tense forms. Storage (vs. composition) was examined
      by probing for past-tense frequency effects and imageability effects--both of
      which are diagnostic tests for storage--while controlling for a number of
      confounding factors. We also examined sex as a factor. Irregular inflected forms,
      which must depend on stored representations, always showed evidence of storage
      (frequency and/or imageability effects), not only across all children, but also
      separately in both sexes. In contrast, for regular forms, which could be either
      stored or composed, only girls showed evidence of storage. This pattern is
      similar to that found in previously-acquired adult data from the same task, with
      the notable exception that development affects which factors influence the
      storage of regulars in females: imageability plays a larger role in girls, and
      frequency in women. Overall, the results suggest that irregular inflected forms
      are always stored (in children and adults, and in both sexes), whereas regulars
      can be either composed or stored, with their storage a function of various item-
      and subject-level factors.

PMID- 24040320
TI  - The structure of spatial networks and communities in bicycle sharing systems.
AB  - Bicycle sharing systems exist in hundreds of cities around the world, with the
      aim of providing a form of public transport with the associated health and
      environmental benefits of cycling without the burden of private ownership and
      maintenance. Five cities have provided research data on the journeys (start and
      end time and location) taking place in their bicycle sharing system. In this
      paper, we employ visualization, descriptive statistics and spatial and network
      analysis tools to explore system usage in these cities, using techniques to
      investigate features specific to the unique geographies of each, and uncovering
      similarities between different systems. Journey displacement analysis
      demonstrates similar journey distances across the cities sampled, and the
      (out)strength rank curve for the top 50 stands in each city displays a similar
      scaling law for each. Community detection in the derived network can identify
      local pockets of use, and spatial network corrections provide the opportunity for
      insight above and beyond proximity/popularity correlations predicted by simple
      spatial interaction models. 

PMID- 24040319
TI  - Drosophila E-cadherin functions in hematopoietic progenitors to maintain
      multipotency and block differentiation.
AB  - A fundamental question in stem cell biology concerns the regulatory strategies
      that control the choice between multipotency and differentiation. Drosophila
      blood progenitors or prohemocytes exhibit key stem cell characteristics,
      including multipotency, quiescence, and niche dependence. As a result, studies of
      Drosophila hematopoiesis have provided important insights into the molecular
      mechanisms that control these processes. Here, we show that E-cadherin is an
      important regulator of prohemocyte fate choice, maintaining prohemocyte
      multipotency and blocking differentiation. These functions are reminiscent of the
      role of E-cadherin in mammalian embryonic stem cells. We also show that mis
      expression of E-cadherin in differentiating hemocytes disrupts the boundary
      between these cells and undifferentiated prohemocytes. Additionally, upregulation
      of E-cadherin in differentiating hemocytes increases the number of intermediate
      cell types expressing the prohemocyte marker, Patched. Furthermore, our studies
      indicate that the Drosophila GATA transcriptional co-factor, U-shaped, is
      required for E-cadherin expression. Consequently, E-cadherin is a downstream
      target of U-shaped in the maintenance of prohemocyte multipotency. In contrast,
      we showed that forced expression of the U-shaped GATA-binding partner, Serpent,
      repressed E-cadherin expression and promoted lamellocyte differentiation. Thus, U
      shaped may maintain E-cadherin expression by blocking the inhibitory activity of
      Serpent. Collectively, these observations suggest that GATA:FOG complex formation
      regulates E-cadherin levels and, thereby, the choice between multipotency and
      differentiation. The work presented in this report further defines the molecular
      basis of prohemocyte cell fate choice, which will provide important insights into
      the mechanisms that govern stem cell biology. 

PMID- 24040321
TI  - The rab11 effector protein FIP1 regulates adiponectin trafficking and secretion.
AB  - Adiponectin is an adipokine secreted by white adipocytes involved in regulating
      insulin sensitivity in peripheral tissues. Secretion of adiponectin in adipocytes
      relies on the endosomal system, however, the intracellular machinery involved in
      mediating adiponectin release is unknown. We have previously reported that
      intracellular adiponectin partially compartmentalizes with rab 5 and rab11,
      markers for the early/sorting and recycling compartments respectively. Here we
      have examined the role of several rab11 downstream effector proteins (rab11 FIPs)
      in regulating adiponectin trafficking and secretion. Overexpression of wild type
      rab11 FIP1, FIP3 and FIP5 decreased the amount of secreted adiponectin expressed
      in HEK293 cells, whereas overexpression of rab11 FIP2 or FIP4 had no effect.
      Furthermore shRNA-mediated depletion of FIP1 enhanced adiponectin release whereas
      knock down of FIP5 decreased adiponectin secretion. Knock down of FIP3 had no
      effect. In 3T3L1 adipocytes, endogenous FIP1 co-distributed intracellularly with
      endogenous adiponectin and FIP1 depletion enhanced adiponectin release without
      altering insulin-mediated trafficking of the glucose transporter Glut4. While
      adiponectin receptors internalized with transferrin receptors, there were no
      differences in transferrin receptor recycling between wild type and FIP1 depleted
      adipocytes. Consistent with its inhibitory role, FIP1 expression was decreased
      during adipocyte differentiation, by treatment with thiazolidinediones, and with
      increased BMI in humans. In contrast, FIP1 expression increased upon exposure of
      adipocytes to TNFalpha. In all, our findings identify FIP1 as a novel protein
      involved in the regulation of adiponectin trafficking and release. 

PMID- 24040323
TI  - Syncopation and the score.
AB  - The score is a symbolic encoding that describes a piece of music, written
      according to the conventions of music theory, which must be rendered as sound
      (e.g., by a performer) before it may be perceived as music by the listener. In
      this paper we provide a step towards unifying music theory with music perception
      in terms of the relationship between notated rhythm (i.e., the score) and
      perceived syncopation. In our experiments we evaluated this relationship by
      manipulating the score, rendering it as sound and eliciting subjective judgments
      of syncopation. We used a metronome to provide explicit cues to the prevailing
      rhythmic structure (as defined in the time signature). Three-bar scores with time
      signatures of 4/4 and 6/8 were constructed using repeated one-bar rhythm
      patterns, with each pattern built from basic half-bar rhythm-components. Our
      manipulations gave rise to various rhythmic structures, including polyrhythms and
      rhythms with missing strong- and/or down-beats. Listeners (N = 10) were asked to
      rate the degree of syncopation they perceived in response to a rendering of each
      score. We observed higher degrees of syncopation in time signatures of 6/8, for
      polyrhythms, and for rhythms featuring a missing down-beat. We also found that
      the location of a rhythm-component within the bar has a significant effect on
      perceived syncopation. Our findings provide new insight into models of
      syncopation and point the way towards areas in which the models may be improved. 

PMID- 24040322
TI  - Patterning in placental 11-B hydroxysteroid dehydrogenase methylation according
      to prenatal socioeconomic adversity.
AB  - BACKGROUND: Prenatal socioeconomic adversity as an intrauterine exposure is
      associated with a range of perinatal outcomes although the explanatory mechanisms
      are not well understood. The development of the fetus can be shaped by the
      intrauterine environment through alterations in the function of the placenta. In
      the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase
      enzyme, which is responsible for the inactivation of maternal cortisol thereby
      protecting the developing fetus from this exposure. This gene is regulated by DNA
      methylation, and this methylation and the expression it controls has been shown
      to be susceptible to a variety of stressors from the maternal environment. The
      association of prenatal socioeconomic adversity and placental HSD11B2 methylation
      has not been examined. Following a developmental origins of disease framework,
      prenatal socioeconomic adversity may alter fetal response to the postnatal
      environment through functional epigenetic alterations in the placenta. Therefore,
      we hypothesized that prenatal socioeconomic adversity would be associated with
      less HSD11B2 methylation. METHODS AND FINDINGS: We examined the association
      between DNA methylation of the HSD11B2 promoter region in the placenta of 444
      healthy term newborn infants and several markers of prenatal socioeconomic
      adversity: maternal education, poverty, dwelling crowding, tobacco use and
      cumulative risk. We also examined whether such associations were sex-specific. We
      found that infants whose mothers experienced the greatest levels of socioeconomic
      adversity during pregnancy had the lowest extent of placental HSD11B2
      methylation, particularly for males. Associations were maintained for maternal
      education when adjusting for confounders (p<0.05). CONCLUSIONS: Patterns of
      HSD11B2 methylation suggest that environmental cues transmitted from the mother
      during gestation may program the developing fetus's response to an adverse
      postnatal environment, potentially via less exposure to cortisol during
      development. Less methylation of placental HSD11B2 may therefore be adaptive and
      promote the effective management of stress associated with social adversity in a
      postnatal environment.

PMID- 24040324
TI  - Resource quantity and quality determine the inter-specific associations between
      ecosystem engineers and resource users in a cavity-nest web.
AB  - While ecosystem engineering is a widespread structural force of ecological
      communities, the mechanisms underlying the inter-specific associations between
      ecosystem engineers and resource users are poorly understood. A proper knowledge
      of these mechanisms is, however, essential to understand how communities are
      structured. Previous studies suggest that increasing the quantity of resources
      provided by ecosystem engineers enhances populations of resource users. In a long
      term study (1995-2011), we show that the quality of the resources (i.e. tree
      cavities) provided by ecosystem engineers is also a key feature that explains the
      inter-specific associations in a tree cavity-nest web. Red-naped sapsuckers
      (Sphyrapicusnuchalis) provided the most abundant cavities (52% of cavities, 0.49
      cavities/ha). These cavities were less likely to be used than other cavity types
      by mountain bluebirds (Sialiacurrucoides), but provided numerous nest-sites (41%
      of nesting cavities) to tree swallows (Tachycinetabicolour). Swallows experienced
      low reproductive outputs in northern flicker (Colaptesauratus) cavities compared
      to those in sapsucker cavities (1.1 vs. 2.1 fledglings/nest), but the highly
      abundant flickers (33% of cavities, 0.25 cavities/ha) provided numerous suitable
      nest-sites for bluebirds (58%). The relative shortage of cavities supplied by
      hairy woodpeckers (Picoidesvillosus) and fungal/insect decay (<10% of cavities
      each, <0.09 cavities/ha) provided fewer breeding opportunities (<15% of nests),
      but represented high quality nest-sites for both bluebirds and swallows. Because
      both the quantity and quality of resources supplied by different ecosystem
      engineers may explain the amount of resources used by each resource user,
      conservation strategies may require different management actions to be
      implemented for the key ecosystem engineer of each resource user. We, therefore,
      urge the incorporation of both resource quantity and quality into models that
      assess community dynamics to improve conservation actions and our understanding
      of ecological communities based on ecosystem engineering. 

PMID- 24040325
TI  - Persistence in epidemic metapopulations: quantifying the rescue effects for
      measles, mumps, rubella and whooping cough.
AB  - Metapopulation rescue effects are thought to be key to the persistence of many
      acute immunizing infections. Yet the enhancement of persistence through spatial
      coupling has not been previously quantified. Here we estimate the metapopulation
      rescue effects for four childhood infections using global WHO reported incidence
      data by comparing persistence on island countries vs all other countries, while
      controlling for key variables such as vaccine cover, birth rates and economic
      development. The relative risk of extinction on islands is significantly higher,
      and approximately double the risk of extinction in mainland countries.
      Furthermore, as may be expected, infections with longer infectious periods tend
      to have the strongest metapopulation rescue effects. Our results quantitate the
      notion that demography and local community size controls disease persistence. 

PMID- 24040326
TI  - Incidence of type 2 diabetes in Japan: a systematic review and meta-analysis.
AB  - BACKGROUND: The definition of incident type 2 diabetes varies across studies;
      hence, the actual incidence of type 2 diabetes in Japan is unclear. Here, we
      reviewed the various definitions of incident type 2 diabetes used in previous
      epidemiologic studies and estimated the diabetes incidence rate in Japan.
      METHODS: We searched for related literature in the MEDLINE, EMBASE, and Ichushi
      databases through September 2012. Two reviewers selected studies that evaluated
      incident type 2 diabetes in the Japanese population. RESULTS: From 1824 relevant
      articles, we included 33 studies with 386,803 participants. The follow-up period
      ranged from 2.3 to 14 years and the studies were initiated between 1980 and 2003.
      The random-effects model indicated that the pooled incidence rate of diabetes was
      8.8 (95% confidence interval, 7.4-10.4) per 1000 person-years. We observed a high
      degree of heterogeneity in the results (I(2) = 99.2%; p < 0.001), with incidence
      rates ranging from 2.3 to 52.6 per 1000 person-years. Three studies based their
      definition of incident type 2 diabetes on self-reports only, 10 on laboratory
      data only, and 20 on self-reports and laboratory data. Compared with studies
      defining diabetes using laboratory data (n = 30; pooled incidence rate = 9.6; 95%
      confidence interval = 8.3-11.1), studies based on self-reports alone tended to
      show a lower incidence rate (n = 3; pooled incidence rate = 4.0; 95% confidence
      interval = 3.2-5.0; p for interaction < 0.001). However, stratified analyses
      could not entirely explain the heterogeneity in the results. CONCLUSIONS: Our
      systematic review and meta-analysis indicated the presence of a high degree of
      heterogeneity, which suggests that there is a considerable amount of uncertainty
      regarding the incidence of type 2 diabetes in Japan. They also suggested that
      laboratory data may be important for the accurate estimation of the incidence of
      type 2 diabetes.

PMID- 24040327
TI  - Identification of a novel and unique transcription factor in the
      intraerythrocytic stage of Plasmodium falciparum.
AB  - The mechanisms of stage-specific gene regulation in the malaria parasite
      Plasmodium falciparum are largely unclear, with only a small number of specific
      regulatory transcription factors (AP2 family) having been identified. In
      particular, the transcription factors that function in the intraerythrocytic
      stage remain to be elucidated. Previously, as a model case for stage-specific
      transcription in the P. falciparum intraerythrocytic stage, we analyzed the
      transcriptional regulation of pf1-cys-prx, a trophozoite/schizont-specific gene,
      and suggested that some nuclear factors bind specifically to the cis-element of
      pf1-cys-prx and enhance transcription. In the present study, we purified nuclear
      factors from parasite nuclear extract by 5 steps of chromatography, and
      identified a factor termed PREBP. PREBP is not included in the AP2 family, and is
      a novel protein with four K-homology (KH) domains. The KH domain is known to be
      found in RNA-binding or single-stranded DNA-binding proteins. PREBP is well
      conserved in Plasmodium species and partially conserved in phylum Apicomplexa. To
      evaluate the effects of PREBP overexpression, we used a transient overexpression
      and luciferase assay combined approach. Overexpression of PREBP markedly enhanced
      luciferase expression under the control of the pf1-cys-prx cis-element. These
      results provide the first evidence of a novel transcription factor that activates
      the gene expression in the malaria parasite intraerythrocytic stage. These
      findings enhance our understanding of the evolution of specific transcription
      machinery in Plasmodium and other eukaryotes. 

PMID- 24040328
TI  - Hemi-nested PCR and RFLP methodologies for identifying blood meals of the Chagas
      disease vector, Triatoma infestans.
AB  - Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted by
      hematophagous reduviid bugs within the subfamily Triatominae. These vectors take
      blood meals from a wide range of hosts, and their feeding behaviors have been
      used to investigate the ecology and epidemiology of T. cruzi. In this study we
      describe two PCR-based methodologies that amplify a fragment of the 16S
      mitochondrial rDNA, aimed to improve the identification of blood meal sources for
      Triatoma infestans: a.--Sequence analyses of two heminested PCRs that allow the
      identification of mammalian and avian species, and b.--restriction fragment
      length polymorphism (RFLP) analysis from the mammalian PCR to identify and
      differentiate multi-host blood meals. Findings from both methodologies indicate
      that host DNA could be detected and the host species identified in samples from
      laboratory reared and field collected triatomines. The implications of this study
      are two-fold. First, these methods can be used in areas where the fauna diversity
      and feeding behavior of the triatomines are unknown. Secondly, the RFLP method
      led to the identification of multi-host DNA from T. infestans gut contents,
      enhancing the information provided by this assay. These tools are important
      contributions for ecological and epidemiological studies of vector-borne
      diseases.

PMID- 24040329
TI  - Effective school actions for mitigating seasonal influenza outbreaks in Niigata,
      Japan.
AB  - BACKGROUND: Japan has implemented various school actions during seasonal
      influenza outbreaks since the 1950's under the School Health Law. However, the
      effective duration, extent, and timing of closures remain unresolved. MATERIALS
      AND METHODS: We conducted a retrospective study on the relationship between
      elementary class closures and influenza outbreak control during four consecutive
      influenza seasons from the 2004-2005 to 2007-2008 school years in Joetsu,
      Niigata, Japan. Among a total of 1,061 classes of 72 schools, 624 cases of
      influenza outbreaks were documented among 61 schools. RESULTS: Class closures
      were carried out in a total of 62 cases in response to influenza outbreak, which
      was defined as a student absentee rate of greater than 10% due to influenza or
      influenza-like illness. Of these cases, two-day class closures were conducted the
      day after reaching a 10% student absentee rate in 28 cases and other types of
      closures were initiated in 34 cases. A markedly higher number of outbreak cases
      ended within one week for two-day class closures compared to the other types of
      closures (82.1% vs. 20.6%, respectively). The significant association between two
      day class closures and interruption of an outbreak within one week was confirmed
      using a multivariable model adjusted for the season, grade, day of the week of an
      outbreak start, and absentee rate on the day of an outbreak start (OR, 3.18; 95%
      CI, 1.12-9.07; p = 0.030). CONCLUSIONS: Our results suggest that a two-day class
      closure carried out the day after reaching a 10% absentee rate is an effective
      approach for mitigating influenza outbreaks in elementary schools.

PMID- 24040330
TI  - Glutathione S-transferase T1, O1 and O2 polymorphisms are associated with
      survival in muscle invasive bladder cancer patients.
AB  - OBJECTIVE: To examine the association of six glutathione transferase (GST) gene
      polymorphisms (GSTT1, GSTP1/rs1695, GSTO1/rs4925, GSTO2/rs156697, GSTM1,
      GSTA1/rs3957357) with the survival of patients with muscle invasive bladder
      cancer and the genotype modifying effect on chemotherapy. PATIENTS AND METHODS: A
      total of 105 patients with muscle invasive bladder cancer were included in the
      study. The follow-up lasted 5 years. The effect of GSTs polymorphisms on
      predicting mortality was analyzed by the Cox proportional hazard models, while
      Kaplan-Meier analysis was performed to assess differences in survival. RESULTS:
      GSTT1 active, GSTO1 Asp140Asp or GSTO2 Asp142Asp genotypes were independent
      predictors of a higher risk of death among bladder cancer patients (HR = 2.5, P =
      0.028; HR = 2.9, P = 0.022; HR = 3.9, P = 0.001; respectively) and significantly
      influenced the overall survival. There was no association between GSTP1, GSTM1
      and GSTA1 gene variants with overall mortality. Only GSTO2 polymorphism showed a
      significant effect on the survival in the subgroup of patients who received
      chemotherapy (P = 0.006). CONCLUSION: GSTT1 active genotype and GSTO1 Asp140Asp
      and GSTO2 Asp142Asp genotypes may have a prognostic/pharmacogenomic role in
      patients with muscle invasive bladder cancer.

PMID- 24040331
TI  - Serdemetan antagonizes the Mdm2-HIF1alpha axis leading to decreased levels of
      glycolytic enzymes.
AB  - Serdemetan (JNJ-26854165), an antagonist to Mdm2, was anticipated to promote the
      activation of p53. While regulation of p53 by Mdm2 is important, Mdm2 also
      regulates numerous proteins involved in diverse cellular functions. We
      investigated if Serdemetan would alter the Mdm2-HIF1alpha axis and affect cell
      survival in human glioblastoma cells independently of p53. Treatment of cells
      with Serdemetan under hypoxia resulted in a decrease in HIF1alpha levels.
      HIF1alpha downstream targets, VEGF and the glycolytic enzymes (enolase,
      phosphoglycerate kinase1/2, and glucose transporter 1), were all decreased in
      response to Serdemetan. The involvement of Mdm2 in regulating gene expression of
      glycolytic enzymes raises the possibility of side effects associated with
      therapeutically targeting Mdm2. 

PMID- 24040332
TI  - Protective effect of hypercapnic acidosis in ischemia-reperfusion lung injury is
      attributable to upregulation of heme oxygenase-1.
AB  - Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung
      injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase
      1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury.
      We investigated whether HO-1 contributes to the protective effects of HCA in
      ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats
      was successfully induced by 40 min of ischemia and 90 min of reperfusion in an
      isolated perfused lung model. The rat lungs were randomly assigned to the control
      group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP),
      an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage
      fluid (BALF) and lung tissues were collected to evaluate the degree of lung
      injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed
      to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or
      absence of HCA. IR caused significant increases in the pulmonary arterial
      pressure, lung weight to body weight and wet/dry ratios, lung weight gain,
      capillary filtration coefficient, lung injury scores, neutrophil infiltration,
      and concentrations of protein and TNF-alpha in the BALF. IR also induced
      degradation of inhibitor of nuclear factor (NF)-kappaB-alpha, increased IkappaB
      kinase (IKK)-beta phosphorylation and nuclear translocation of NF-kappaB, and up
      regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein
      expression and increased the number of active caspase-3 stained cells. HCA
      treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF
      kappaB signaling, inhibited apoptosis, and significantly attenuated IR-induced
      changes. Treatment with ZnPP partially blocked the protective effect of HCA. In
      addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-kappaB
      signaling in A549 cells subjected to H/R. In conclusion, the protective effect of
      HCA in IR lung injury in rats was mediated in part by the anti-inflammatory and
      anti-apoptotic action of HO-1. 

PMID- 24040333
TI  - Chitosan nanoencapsulated exogenous trypsin biomimics zymogen-like enzyme in fish
      gastrointestinal tract.
AB  - Exogenous proteolytic enzyme supplementation is required in certain disease
      conditions in humans and animals and due to compelling reasons on use of more
      plant protein ingredients and profitability in animal feed industry. However,
      limitations on their utility in diet are imposed by their pH specificity,
      thermolabile nature, inhibition due to a variety of factors and the possibility
      of intestinal damage. For enhancing the efficacy and safety of exogenous trypsin,
      an efficient chitosan (0.04%) nanoencapsulation-based controlled delivery system
      was developed. An experiment was conducted for 45 days to evaluate
      nanoencapsulated trypsin (0.01% and 0.02%) along with 0.02% bare trypsin and 0.4%
      chitosan nanoparticles against a control diet on productive efficiency (growth
      rate, feed conversion and protein efficiency ratio), organo-somatic indices,
      nutrient digestibility, tissue enzyme activities, hematic parameters and
      intestinal histology of the fish Labeo rohita. All the synthesized nanoparticles
      were of desired characteristics. Enhanced fish productive efficiency using
      nanoencapsulated trypsin over its bare form was noticed, which corresponded with
      enhanced (P<0.01) nutrient digestibility, activity of intestinal protease, liver
      and muscle tissue transaminases (alanine and aspartate) and dehydrogenases
      (lactate and malate), serum blood urea nitrogen and serum protein profile.
      Intestinal tissues of fish fed with 0.02% bare trypsin showed broadened, marked
      foamy cells with lipid vacuoles. However, villi were healthier in appearance with
      improved morphological features in fish fed with nanoencapsulated trypsin than
      with bare trypsin, and the villi were longer in fish fed with 0.01%
      nanoencapsulated trypsin than with 0.02% nanoencapsulated trypsin. The result of
      this premier experiment shows that nanoencapsulated trypsin mimics zymogen-like
      proteolytic activity via controlled release, and hence the use of 0.01%
      nanoencapsulated trypsin (in chitosan nanoparticles) over bare trypsin can be
      favored as a dietary supplement in animals and humans. 

PMID- 24040334
TI  - An innovative cascade system for simultaneous separation of multiple cell types.
AB  - Isolation of different cell types from one sample by fluorescence activated cell
      sorting is standard but expensive and time consuming. Magnetic separation is more
      cost effective and faster by but requires substantial effort. An innovative
      pluriBead-cascade cell isolation system (pluriSelect GmbH, Leipzig, Germany)
      simultaneously separates two or more different cell types. It is based on
      antibody-mediated binding of cells to beads of different size and their isolation
      with sieves of different mesh-size. For the first time, we validated the
      pluriSelect system for simultaneous separation of CD4+- and CD8+-cells from human
      EDTA-blood samples. Results were compared with those obtained by magnetic
      activated cell sorting (MACS; two steps -first isolation of CD4+, then restaining
      of the residual cell suspension with anti-human CD8+ MACS antibody followed by
      the second isolation). pluriSelect separation was done in whole blood, MACS
      separation on density gradient isolated mononuclear cells. Isolated and residual
      cells were immunophenotyped by 7-color 9-marker panel (CD3; CD16/56; CD4; CD8;
      CD14; CD19; CD45; HLA-DR) using flow cytometry. Cell count, purity, yield and
      viability (7-AAD exclusion) were determined. There were no significant
      differences between both systems regarding purity (MACS (median[range]: 92.4%
      [91.5-94.9] vs. pluriSelect 95% [94.9-96.8])) of CD4+ cells, however CD8+
      isolation showed lower purity by MACS (74.8% [67.6-77.9], pluriSelect 89.9% [89.0
      95.7]). Yield was not significantly different for CD4 (MACS 58.5% [54.1-67.5],
      pluriSelect 67.9% [56.8-69.8]) and for CD8 (MACS 57.2% [41.3-72.0], pluriSelect
      67.2% [60.0-78.5]). Viability was slightly higher with MACS for CD4+ (98.4% [97.8
      99.0], pluriSelect 94.1% [92.1-95.2]) and for CD8+-cells (98.8% [98.3-99.1],
      pluriSelect 86.7% [84.2-89.9]). pluriSelect separation was substantially faster
      than MACS (1h vs. 2.5h) and no pre-enrichment steps were necessary. In
      conclusion, pluriSelect is a fast, simple and gentle system for efficient
      simultaneous separation of two and more cell subpopulation directly from whole
      blood and provides a simple alternative to magnetic separation. 

PMID- 24040335
TI  - Structure of the NheA component of the Nhe toxin from Bacillus cereus:
      implications for function.
AB  - The structure of NheA, a component of the Bacillus cereus Nhe tripartite toxin,
      has been solved at 2.05 A resolution using selenomethionine multiple-wavelength
      anomalous dispersion (MAD). The structure shows it to have a fold that is similar
      to the Bacillus cereus Hbl-B and E. coli ClyA toxins, and it is therefore a
      member of the ClyA superfamily of alpha-helical pore forming toxins (alpha-PFTs),
      although its head domain is significantly enlarged compared with those of ClyA or
      Hbl-B. The hydrophobic beta-hairpin structure that is a characteristic of these
      toxins is replaced by an amphipathic beta-hairpin connected to the main structure
      via a beta-latch that is reminiscent of a similar structure in the beta-PFT
      Staphylococcus aureus alpha-hemolysin. Taken together these results suggest that,
      although it is a member of an archetypal alpha-PFT family of toxins, NheA may be
      capable of forming a beta rather than an alpha pore. 

PMID- 24040336
TI  - Reduction of microRNA-206 contributes to the development of bronchopulmonary
      dysplasia through up-regulation of fibronectin 1.
AB  - OBJECTIVE: To characterize microRNA-206 (miR-206) in the development of
      bronchopulmonary dysplasia (BPD). DESIGN/METHODS: We assessed the expression of
      miR-206 in BPD mouse lung tissues and blood samples of BPD patients by
      quantitative real-time PCR. Then, the role of miR-206 in regulating cell biology
      were examined by XTT assay, flow cytometry, transwell invasion assay, wound
      healing assay and adhesion assay in vitro. Furthermore, luciferase reporter
      assay, real-time PCR, western blot and Immunofluorescence staining were performed
      to figure out the target gene of miR-206. RESULTS: A reduction in expression of
      miR-206 was observed in BPD mice compared with controls and in BPD patients
      compared with controls. miR-206 overexpression significantly induced cell
      apoptosis, reduced cell proliferation, migration and adhesion abilities, whereas
      the inhibition of miR-206 expression had the opposite effect. Fibronectin 1 (FN1)
      is a direct target of miR-206, and fn 1 can be transcriptionally and
      translationally regulated by miR-206. Down-regulation of miR-206 modulates
      biological functions of the cells, at least in part, by increasing the level of
      fn 1. Furthermore, fn 1 expression levels were increased in the BPD mice and BPD
      patients. CONCLUSIONS: The expression of miR-206 and its target gene, fn 1, may
      contribute to the progression of BPD.

PMID- 24040337
TI  - Measles outbreak in Macedonia: epidemiological, clinical and laboratory findings
      and identification of susceptible cohorts.
AB  - OBJECTIVES: Despite a 92-99% national vaccination coverage since 2000, the former
      Yugoslav Republic of Macedonia experienced a large measles outbreak between 2010
      and 2011. Here we investigate the characteristics of patients hospitalized during
      this outbreak at the Clinic of Infectious Diseases in Skopje. METHODS:
      Epidemiological, clinical and laboratory data of 284 measles patients, including
      251 from Skopje (43.80% of the 573 reported cases) and 33 from elsewhere in
      Macedonia were collected. RESULTS: The most affected age groups were children up
      to 4 years of age and adolescents/adults of 15 years and older. Most patients
      were unvaccinated (n=263, 92.61%) and many had non-Macedonian nationalities
      (n=156, 54.93%) or belonged to the Roma ethnicity (n=73, 25.70%).
      Bronchopneumonia and diarrhea were the most common complications. Eighty-two out
      of 86 tested patients (95.35%) had measles-specific IgM antibodies. The outbreak
      was caused by the measles variant D4-Hamburg. CONCLUSIONS: The epidemic
      identified pockets of susceptibles in Skopje and indicated that additional
      vaccination opportunities in particular for people with non-Macedonian
      nationality and traveler communities are warranted to ensure efficient measles
      control in Macedonia. The high attack rate among children of less than 1 year
      suggests that vaccination before 12 months of age should be considered in high
      risk settings.

PMID- 24040338
TI  - Cognitive reserve in granulin-related frontotemporal dementia: from preclinical
      to clinical stages.
AB  - OBJECTIVE: Consistent with the cognitive reserve hypothesis, higher education and
      occupation attainments may help persons with neurodegenerative dementias to
      better withstand neuropathology before developing cognitive impairment. We tested
      here the cognitive reserve hypothesis in patients with frontotemporal dementia
      (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in
      presymptomatic GRN mutation carriers (aGRN+). METHODS: Education and occupation
      attainments were assessed and combined to define Reserve Index (RI) in 32 FTD
      patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional
      connectivity were estimated by resting state fMRI, focusing on the salience
      network (SN), executive network (EN) and bilateral frontoparietal networks
      (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating
      Scale. RESULTS: In FTD patients higher level of premorbid cognitive reserve was
      associated with reduced connectivity within the SN and the EN. EN was more
      involved in FTD patients without GRN mutations, while SN was more affected in GRN
      pathology. In aGRN+, cognitive reserve was associated with reduced SN.
      CONCLUSIONS: This study suggests that cognitive reserve modulates functional
      connectivity in patients with FTD, even in monogenic disease. In GRN inherited
      FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical
      stages.

PMID- 24040339
TI  - Functional analysis in mouse embryonic stem cells reveals wild-type activity for
      three MSH6 variants found in suspected Lynch syndrome patients.
AB  - Lynch syndrome confers an increased risk to various types of cancer, in
      particular early onset colorectal and endometrial cancer. Mutations in mismatch
      repair (MMR) genes underlie Lynch syndrome, with the majority of mutations found
      in MLH1 and MSH2. Mutations in MSH6 have also been found but these do not always
      cause a clear cancer predisposition phenotype and MSH6-defective tumors often do
      not show the standard characteristics of MMR deficiency, such as microsatellite
      instability. In particular, the consequences of MSH6 missense mutations are
      challenging to predict, which further complicates genetic counseling. We have
      previously developed a method for functional characterization of MSH2 missense
      mutations of unknown significance. This method is based on endogenous gene
      modification in mouse embryonic stem cells using oligonucleotide-directed gene
      targeting, followed by a series of functional assays addressing the MMR
      functions. Here we have adapted this method for the characterization of MSH6
      missense mutations. We recreated three MSH6 variants found in suspected Lynch
      syndrome families, MSH6-P1087R, MSH6-R1095H and MSH6-L1354Q, and found all three
      to behave like wild type MSH6. Thus, despite suspicion for pathogenicity from
      clinical observations, our approach indicates these variants are not disease
      causing. This has important implications for counseling of mutation carriers. 

PMID- 24040340
TI  - C22:0- and C24:0-dihydroceramides confer mixed cytotoxicity in T-cell acute
      lymphoblastic leukemia cell lines.
AB  - We previously reported that fenretinide (4-HPR) was cytotoxic to acute
      lymphoblastic leukemia (ALL) cell lines in vitro in association with increased
      levels of de novo synthesized dihydroceramides, the immediate precursors of
      ceramides. However, the cytotoxic potentials of native dihydroceramides have not
      been defined. Therefore, we determined the cytotoxic effects of increasing
      dihydroceramide levels via de novo synthesis in T-cell ALL cell lines and whether
      such cytotoxicity was dependent on an absolute increase in total dihydroceramide
      mass versus an increase of certain specific dihydroceramides. A novel method
      employing supplementation of individual fatty acids, sphinganine, and the
      dihydroceramide desaturase-1 (DES) inhibitor, GT-11, was used to increase de novo
      dihydroceramide synthesis and absolute levels of specific dihydroceramides and
      ceramides. Sphingolipidomic analyses of four T-cell ALL cell lines revealed
      strong positive correlations between cytotoxicity and levels of C22:0
      dihydroceramide (rho = 0.74-0.81, P <= 0.04) and C24:0-dihydroceramide (rho =
      0.84-0.90, P <= 0.004), but not between total or other individual
      dihydroceramides, ceramides, or sphingoid bases or phosphorylated derivatives.
      Selective increase of C22:0- and C24:0-dihydroceramide increased level and flux
      of autophagy marker, LC3B-II, and increased DNA fragmentation (TUNEL assay) in
      the absence of an increase of reactive oxygen species; pan-caspase inhibition
      blocked DNA fragmentation but not cell death. C22:0-fatty acid supplemented to 4
      HPR treated cells further increased C22:0-dihydroceramide levels (P <= 0.001) and
      cytotoxicity (P <= 0.001). These data demonstrate that increases of specific
      dihydroceramides are cytotoxic to T-cell ALL cells by a caspase-independent,
      mixed cell death mechanism associated with increased autophagy and suggest that
      dihydroceramides may contribute to 4-HPR-induced cytotoxicity. The targeted
      increase of specific acyl chain dihydroceramides may constitute a novel
      anticancer approach. 

PMID- 24040341
TI  - Fashion vs. function in cultural evolution: the case of dog breed popularity.
AB  - We investigate the relationship between characteristics of dog breeds and their
      popularity between years 1926 and 2005. We consider breed health, longevity, and
      behavioral qualities such as aggressiveness, trainability, and fearfulness. We
      show that a breed's overall popularity, fluctuations in popularity, and rates of
      increase and decrease around popularity peaks show typically no correlation with
      these breed characteristics. One exception is the finding that more popular
      breeds tend to suffer from more inherited disorders. Our results support the
      hypothesis that dog breed popularity has been primarily determined by fashion
      rather than function. 

PMID- 24040342
TI  - Effect of DNA extraction methods and sampling techniques on the apparent
      structure of cow and sheep rumen microbial communities.
AB  - Molecular microbial ecology techniques are widely used to study the composition
      of the rumen microbiota and to increase understanding of the roles they play.
      Therefore, sampling and DNA extraction methods that result in adequate yields of
      microbial DNA that also accurately represents the microbial community are
      crucial. Fifteen different methods were used to extract DNA from cow and sheep
      rumen samples. The DNA yield and quality, and its suitability for downstream PCR
      amplifications varied considerably, depending on the DNA extraction method used.
      DNA extracts from nine extraction methods that passed these first quality
      criteria were evaluated further by quantitative PCR enumeration of microbial
      marker loci. Absolute microbial numbers, determined on the same rumen samples,
      differed by more than 100-fold, depending on the DNA extraction method used. The
      apparent compositions of the archaeal, bacterial, ciliate protozoal, and fungal
      communities in identical rumen samples were assessed using 454 Titanium
      pyrosequencing. Significant differences in microbial community composition were
      observed between extraction methods, for example in the relative abundances of
      members of the phyla Bacteroidetes and Firmicutes. Microbial communities in
      parallel samples collected from cows by oral stomach-tubing or through a rumen
      fistula, and in liquid and solid rumen digesta fractions, were compared using one
      of the DNA extraction methods. Community representations were generally similar,
      regardless of the rumen sampling technique used, but significant differences in
      the abundances of some microbial taxa such as the Clostridiales and the
      Methanobrevibacter ruminantium clade were observed. The apparent microbial
      community composition differed between rumen sample fractions, and Prevotellaceae
      were most abundant in the liquid fraction. DNA extraction methods that involved
      phenol-chloroform extraction and mechanical lysis steps tended to be more
      comparable. However, comparison of data from studies in which different sampling
      techniques, different rumen sample fractions or different DNA extraction methods
      were used should be avoided. 

PMID- 24040343
TI  - Oxygen and an extracellular phase transition independently control central
      regulatory genes and conidiogenesis in Aspergillus fumigatus.
AB  - Conidiogenesis is the primary process for asexual reproduction in filamentous
      fungi. As the conidia resulting from the conidiogenesis process are primarily
      disseminated via air currents and/or water, an outstanding question has been how
      fungi recognize aerial environments suitable for conidial development. In this
      study, we documented the somewhat complex development of the conidia-bearing
      structures, termed conidiophores, from several Aspergillus species in a
      subsurface (gel-phase) layer of solid media. A subset of the isolates studied was
      able to develop conidiophores in a gel-phase environment, but exposure to the
      aeriform environment was required for the terminal developmental transition from
      phialide cells to conidia. The remaining Aspergilli could not initiate the
      conidiogenesis process until they were exposed to the aeriform environment. Our
      observations of conidiophore development in high or low oxygen conditions in both
      aeriform and gel-phase environments revealed that oxygen and the aeriform state
      are positive environmental factors for inducing conidiogenesis in most of the
      aspergilli tested in this study. Transcriptional analysis using A. fumigatus
      strain AF293 confined to either the aeriform or gel-phase environments revealed
      that expression of a key regulatory gene for conidiophore development (AfubrlA)
      is facilitated by oxygen while expression of another regulatory gene controlling
      conidia formation from phialides (AfuabaA) was repressed regardless of oxygen
      levels in the gel-embedded environment. Furthermore, by comparing the
      developmental behavior of conidiation-defective mutants lacking genes controlling
      various regulatory checkpoints throughout the conidiogenesis pathway, we propose
      that this aerial response by the fungus requires both oxygen and the phase
      transition (solid to aeriform), with these environmental signals integrating into
      the upstream regulatory pathway and central regulatory pathway of conidiogenesis,
      respectively. Our findings provide not only novel insight into how fungi respond
      to an aerial environment to trigger development for airborne conidia production
      but also the relationship between environmental factors and conidiogenesis
      regulation in aspergilli. 

PMID- 24040344
TI  - Mapping monkeypox transmission risk through time and space in the Congo Basin.
AB  - Monkeypox is a major public health concern in the Congo Basin area, with changing
      patterns of human case occurrences reported in recent years. Whether this trend
      results from better surveillance and detection methods, reduced proportions of
      vaccinated vs. non-vaccinated human populations, or changing environmental
      conditions remains unclear. Our objective is to examine potential correlations
      between environment and transmission of monkeypox events in the Congo Basin. We
      created ecological niche models based on human cases reported in the Congo Basin
      by the World Health Organization at the end of the smallpox eradication campaign,
      in relation to remotely-sensed Normalized Difference Vegetation Index datasets
      from the same time period. These models predicted independent spatial subsets of
      monkeypox occurrences with high confidence; models were then projected onto
      parallel environmental datasets for the 2000s to create present-day monkeypox
      suitability maps. Recent trends in human monkeypox infection are associated with
      broad environmental changes across the Congo Basin. Our results demonstrate that
      ecological niche models provide useful tools for identification of areas suitable
      for transmission, even for poorly-known diseases like monkeypox. 

PMID- 24040345
TI  - Epilepsy in Cambodia-treatment aspects and policy implications: a population
      based representative survey.
AB  - INTRODUCTION: We tested two treatment strategies to determine: treatment (a)
      prognosis (seizure frequency, mortality, suicide, and complications), (b) safety
      and adherence of treatment, (c) self-reported satisfaction with treatment and
      self-reported productivity, and policy aspects (a) number of required tablets for
      universal treatment (NRT), (b) cost of management, (c) manpower-gap and
      requirements for scaling-up of epilepsy care. METHODS: We performed a random
      cluster survey (N = 16510) and identified 96 cases (>=1 year of age) in 24
      villages. They were screened by using a validated instrument and diagnosed by the
      neurologists. International guidelines were used for defining and classifying
      epilepsy. All were given phenobarbital or valproate (cost-free) in two manners
      patient's door-steps (March 2009-March 2010, primary-treatment-period, PTP) and
      treatment through health-centers (March 2010-June 2011, treatment-continuation
      period, TCP). The emphasis was to start on a minimum dosage and regime, without
      any polytherapy, according to the age of the recipients. No titration was done.
      Seizure-frequency was monthly and self-reported. RESULTS: The number of seizures
      reduced from 12.6 (pre-treatment) to 1.2 (end of PTP), following which there was
      an increase to 3.4 (end of TCP). Between start of PTP and end of TCP, >60.0%
      became and remained seizure-free. During TCP, ~26.0% went to health centers to
      collect their treatment. Complications reduced from 12.5% to 4.2% between start
      and end of PTP and increased to 17.2% between start and end of TCP. Adverse
      events reduced from 46.8% to 16.6% between start and end of PTP. Nearly 33
      million phenobarbital 100 mg tablets are needed in Cambodia. CONCLUSIONS:
      Epilepsy responded sufficiently well to the conventional treatment, even when
      taken at a minimal dosage and a simple daily regimen, without any polytherapy.
      This is yet another confirmation that it is possible to substantially reduce
      direct burden of epilepsy through means that are currently available to us.

PMID- 24040346
TI  - Regulatory scientific advice on non-inferiority drug trials.
AB  - The active-controlled trial with a non-inferiority design has gained popularity
      in recent years. However, non-inferiority trials present some methodological
      challenges, especially in determining the non-inferiority margin. Regulatory
      guidelines provide some general statements on how a non-inferiority trial should
      be conducted. Moreover, in a scientific advice procedure, regulators give
      companies the opportunity to discuss critical trial issues prior to the start of
      the trial. The aim of this study was to identify potential issues that may
      benefit from more explicit guidance by regulators. To achieve this, we collected
      and analyzed questions about non-inferiority trials posed by applicants for
      scientific advice in Europe in 2008 and 2009, as well as the responses given by
      the European Medicines Agency (EMA). In our analysis we included 156 final
      letters of advice from 2008 and 2009, addressed to 94 different applicants
      (manufacturers). Our analysis yielded two major findings: (1) applicants
      frequently asked questions 'whether' and 'how' to conduct a non-inferiority
      trial, 26% and 74%, respectively, and (2) the EMA regulators seem mainly
      concerned about the choice of the non-inferiority margin in non-inferiority
      trials (36% of total regulatory answers). In 40% of the answers, the EMA
      recommended using a stricter margin, and in 10% of the answers regarding non
      inferiority margins, the EMA questioned the justification of the proposed non
      inferiority margin. We conclude that there are still difficulties in selecting
      the appropriate methodology for non-inferiority trials. Straightforward and
      harmonized guidance regarding non-inferiority trials is required, for example on
      whether it is necessary to conduct such a trial and how the non-inferiority
      margin is determined. It is unlikely that regulatory guidelines can cover all
      therapeutic areas; therefore, in some cases regulatory scientific advice may be
      used as an opportunity for tailored advice. 

PMID- 24040347
TI  - Were rivers flowing across the Sahara during the last interglacial? Implications
      for human migration through Africa.
AB  - Human migration north through Africa is contentious. This paper uses a novel
      palaeohydrological and hydraulic modelling approach to test the hypothesis that
      under wetter climates c.100,000 years ago major river systems ran north across
      the Sahara to the Mediterranean, creating viable migration routes. We confirm
      that three of these now buried palaeo river systems could have been active at the
      key time of human migration across the Sahara. Unexpectedly, it is the most
      western of these three rivers, the Irharhar river, that represents the most
      likely route for human migration. The Irharhar river flows directly south to
      north, uniquely linking the mountain areas experiencing monsoon climates at these
      times to temperate Mediterranean environments where food and resources would have
      been abundant. The findings have major implications for our understanding of how
      humans migrated north through Africa, for the first time providing a quantitative
      perspective on the probabilities that these routes were viable for human
      habitation at these times. 

PMID- 24040348
TI  - Global population trends and human use patterns of Manta and Mobula rays.
AB  - Despite being the world's largest rays and providing significant revenue through
      dive tourism, little is known about the population status, exploitation and trade
      volume of the Mobulidae (mobulids; Manta and Mobula spp.). There is anecdotal
      evidence, however, that mobulid populations are declining, largely due to the
      recent emergence of a widespread trade for their gill rakers, which is reflected
      in increasing Food and Agriculture Organization landings trends. Here, we present
      results from two dedicated diver surveys, one from the eManta project, which
      includes summary observations from ninety 10 degrees x10 degrees  regions with
      ~200-62,000 dives per region, and the other from the Reef Environmental Education
      Foundation, which includes spatially more detailed observations from 3 regions
      with ~4,000-118,000 dives per region. We show that mobulids as a group, which
      includes eleven species, have globally and regionally restricted distributions,
      typically have low sighting frequency (<1% of dives) and aggregate in only a few
      locations. Of the regions surveyed by divers, almost half (47%) report declining
      mobulid sightings over the last decade. Divers indicate that although mobulid
      ecotourism occurs in many regions (45% of those reported, n = 41) they are
      considered protected in only 32% of the regions. Mobulids being fished or sold in
      local markets were reported from 16% and 12% of regions, respectively, with most
      being adjacent to mobulid abundance hotspot and ecotourism regions (e.g. Sri
      Lanka, Indonesia, east Africa). Identification of regions where ecotourism and
      exploitation are at odds could help prioritize conservation efforts.
      Vulnerability analysis, using life history characteristics, indicates that Manta
      spp. are vulnerable to exploitation, tolerating only low fishing mortality rates;
      data limitations prohibited such analysis for Mobula spp. Our analyses support
      previous studies in showing the need for improved conservation and monitoring
      efforts, and suggest that international and enforceable management policies are
      required to prevent further population decline. 

PMID- 24040349
TI  - Fast-evolving homoplastic traits are best for species identification in a group
      of neotropical wasps.
AB  - Biological characters can be employed for both taxonomy and phylogenetics, but is
      conscripting characters for double duty a good idea? We explore the evolution of
      characters designed for taxonomic diagnosis in Costa Rican heterospiline wasps, a
      hyperdiverse lineage of parasitoid Braconidae, by mapping them to a robust multi
      locus molecular phylogeny. We discover a strong positive relationship between the
      amount of evolutionary change a character undergoes and how broadly useful the
      characters are in the context of an interactive identification key--e.g., how
      evenly the character states are distributed among taxa. The empirical finding
      that fast characters are the most useful for species identification supports the
      idea that characters designed for taxonomic diagnoses are likely to underperform-
      or be positively misleading--in phylogenetic analyses.

PMID- 24040350
TI  - Transcriptome analysis of encystation in Entamoeba invadens.
AB  - Encystation is an essential differentiation process for the completion of the
      life cycle of a group of intestinal protozoa including Entamoeba histolytica, the
      causative agent of intestinal and extraintestinal amebiasis. However, regulation
      of gene expression during encystation is poorly understood. To comprehensively
      understand the process at the molecular level, the transcriptomic profiles of E.
      invadens, which is a related reptilian species that causes an invasive disease
      similar to that of E. histolytica, was investigated during encystation. Using a
      custom-generated Affymetrix platform microarray, we performed time course (0.5,
      2, 8, 24, 48, and 120 h) gene expression analysis of encysting E. invadens. ANOVA
      analysis revealed that a total of 1,528 genes showed >=3 fold up-regulation at
      one or more time points, relative to the trophozoite stage. Of these modulated
      genes, 8% (116 genes) were up-regulated at the early time points (0.5, 2 and 8h),
      while 63% (962 genes) were up-regulated at the later time points (24, 48, and 120
      h). Twenty nine percent (450 genes) are either up-regulated at 2 to 5 time points
      or constitutively up-regulated in both early and late stages. Among the up
      regulated genes are the genes encoding transporters, cytoskeletal proteins,
      proteins involved in vesicular trafficking (small GTPases), Myb transcription
      factors, cysteine proteases, components of the proteasome, and enzymes for chitin
      biosynthesis. This study represents the first kinetic analysis of gene expression
      during differentiation from the invasive trophozoite to the dormant, infective
      cyst stage in Entamoeba. Functional analysis on individual genes and their
      encoded products that are modulated during encystation may lead to the discovery
      of targets for the development of new chemotherapeutics that interfere with stage
      conversion of the parasite. 

PMID- 24040351
TI  - Eye-head coordination abnormalities in schizophrenia.
AB  - BACKGROUND: Eye-movement abnormalities in schizophrenia are a well-established
      phenomenon that has been observed in many studies. In such studies, visual
      targets are usually presented in the center of the visual field, and the
      subject's head remains fixed. However, in every-day life, targets may also appear
      in the periphery. This study is among the first to investigate eye and head
      movements in schizophrenia by presenting targets in the periphery of the visual
      field. METHODOLOGY/PRINCIPAL FINDINGS: Two different visual recognition tasks,
      color recognition and Landolt orientation tasks, were presented at the periphery
      (at a visual angle of 55 degrees  from the center of the field of view). Each
      subject viewed 96 trials, and all eye and head movements were simultaneously
      recorded using video-based oculography and magnetic motion tracking of the head.
      Data from 14 patients with schizophrenia and 14 controls were considered. The
      patients had similar saccadic latencies in both tasks, whereas controls had
      shorter saccadic latencies in the Landolt task. Patients performed more head
      movements, and had increased eye-head offsets during combined eye-head shifts
      than controls. CONCLUSIONS/SIGNIFICANCE: Patients with schizophrenia may not be
      able to adapt to the two different tasks to the same extent as controls, as seen
      by the former's task-specific saccadic latency pattern. This can be interpreted
      as a specific oculomotoric attentional dysfunction and may support the hypothesis
      that schizophrenia patients have difficulties determining the relevance of
      stimuli. Patients may also show an uneconomic over-performance of head-movements,
      which is possibly caused by alterations in frontal executive function that impair
      the inhibition of head shifts. In addition, a model was created explaining 93% of
      the variance of the response times as a function of eye and head amplitude, which
      was only observed in the controls, indicating abnormal eye-head coordination in
      patients with schizophrenia.

PMID- 24040352
TI  - Rare failures of DNA barcodes [corrected] to separate morphologically distinct
      species in a biodiversity survey of Iberian leaf beetles.
AB  - During a survey of genetic and species diversity patterns of leaf beetle
      (Coleoptera: Chrysomelidae) assemblages across the Iberian Peninsula we found a
      broad congruence between morphologically delimited species and variation in the
      cytochrome oxidase (cox1) gene. However, one species pair each in the genera
      Longitarsus Berthold and Pachybrachis Chevrolat was inseparable using molecular
      methods, whereas diagnostic morphological characters (including male or female
      genitalia) unequivocally separated the named species. Parsimony haplotype
      networks and maximum likelihood trees built from cox1 showed high genetic
      structure within each species pair, but no correlation with the morphological
      types and neither with geographic distributions. This contrasted with all
      analysed congeneric species, which were recovered as monophyletic. A limited
      number of specimens were sequenced for the nuclear 18S rRNA gene, which showed no
      or very limited variation within the species pair and no separation of
      morphological types. These results suggest that processes of lineage sorting for
      either group are lagging behind the clear morphological and presumably
      reproductive separation. In the Iberian chrysomelids, incongruence between DNA
      based and morphological delimitations is a rare exception, but the discovery of
      these species pairs may be useful as an evolutionary model for studying the
      process of speciation in this ecological and geographical setting. In addition,
      the study of biodiversity patterns based on DNA requires an evolutionary
      understanding of these incongruences and their potential causes. 

PMID- 24040353
TI  - Comparative efficiency of HIV-1-infected T cell killing by NK cells, monocytes
      and neutrophils.
AB  - HIV-1 infected cells are eliminated in infected individuals by a variety of
      cellular mechanisms, the best characterized of which are cytotoxic T cell and NK
      cell-mediated killing. An additional antiviral mechanism is antibody-dependent
      cellular cytotoxicity. Here we use primary CD4(+) T cells infected with the BaL
      clone of HIV-1 as target cells and autologous NK cells, monocytes, and
      neutrophils as effector cells, to quantify the cytotoxicity mediated by the
      different effectors. This was carried out in the presence or absence of HIV-1
      specific antiserum to assess antibody-dependent cellular cytotoxicity. We show
      that at the same effector to target ratio, NK cells and monocytes mediate similar
      levels of both antibody-dependent and antibody-independent killing of HIV-1
      infected T cells. Neutrophils mediated significant antibody-dependent killing of
      targets, but were less effective than monocytes or NK cells. These data have
      implications for acquisition and control of HIV-1 in natural infection and in the
      context of vaccination. 

PMID- 24040354
TI  - Effects of EZH2 polymorphisms on susceptibility to and pathological development
      of hepatocellular carcinoma.
AB  - BACKGROUND: The enhancer of zeste 2 (EZH2) gene encodes the histone
      methyltransferase that is the catalytic component of the polycomb repressive
      complex-2, which initiates epigenetic silencing of genes. The expression level of
      EZH2 in hepatocellular carcinoma (HCC) is highly correlated with tumor
      progression; however, it has not been determined if specific EZH2 genetic
      variants are associated with the risk of HCC. This study investigated the
      potential associations of EZH2 single-nucleotide polymorphisms with HCC
      susceptibility and its clinicopathologic characteristics. METHODOLOGY/PRINCIPAL
      FINDINGS: A total of 220 HCC patients and 552 cancer-free controls were analyzed
      for four EZH2 single-nucleotide polymorphisms (rs6950683, rs2302427, rs3757441,
      and rs41277434) using real-time PCR genotyping. After adjusting for other co
      variants, the individuals carrying at least one C allele at EZH2 rs6950683 and
      rs3757441 had a 0.611-fold and a 0.660-fold lower risk of developing HCC than did
      wild-type (TT) carriers, respectively. The CCCA or CCTA haplotype among the four
      EZH2 sites (rs6950683, rs2302427, rs3757441, and rs41277434), respectively, was
      also associated with a reduced risk of HCC. Furthermore, HCC patients who carried
      at least one C allele at rs6950683 or rs3757441 had a higher lymph-node
      metastasis risk but a lower liver-cirrhosis risk than did patients carrying the
      wild-type allele. CONCLUSIONS: The rs6950683 and rs3757441 polymorphic genotypes
      of EZH2 might contribute to the prediction of susceptibility to and pathological
      development of HCC. This is the first study to provide insight into risk factors
      associated with EZH2 variants in carcinogenesis of HCC in Taiwan.

PMID- 24040355
TI  - The presence of modifiable residues in the core peptide part of precursor nisin
      is not crucial for precursor nisin interactions with NisB- and NisC.
AB  - Precursor nisin is a model posttranslationally modified precursor lantibiotic
      that can be structurally divided into a leader peptide sequence and a modifiable
      core peptide part. The nisin core peptide clearly plays an important role in the
      precursor nisin-nisin modification enzymes interactions, since it has previously
      been shown that the construct containing only the nisin leader sequence is not
      sufficient to pull-down the nisin modification enzymes NisB and NisC. Serines and
      threonines in the core peptide part are the residues that NisB specifically
      dehydrates, and cysteines are the residues that NisC stereospecifically couples
      to the dehydrated amino acids. Here, we demonstrate that increasing the number of
      negatively charged residues in the core peptide part of precursor nisin, which
      are absent in wild-type nisin, does not abolish binding of precursor nisin to the
      modification enzymes NisB and NisC, but dramatically decreases the antimicrobial
      potency of these nisin mutants. An unnatural precursor nisin variant lacking all
      serines and threonines in the core peptide part and an unnatural precursor nisin
      variant lacking all cysteines in the core peptide part still bind the nisin
      modification enzymes NisB and NisC, suggesting that these residues are not
      essential for direct interactions with the nisin modification enzymes NisB and
      NisC. These results are important for lantibiotic engineering studies.

PMID- 24040356
TI  - The contribution of Orai(CRACM)1 and Orai(CRACM)2 channels in store-operated Ca2+
      entry and mediator release in human lung mast cells.
AB  - BACKGROUND: The influx of extracellular Ca(2+) into mast cells is critical for
      the FcepsilonR1-dependent release of preformed granule-derived mediators and
      newly synthesised autacoids and cytokines. The Orai(CRACM) ion channel family
      provide the major pathway through which this Ca(2+) influx occurs. However the
      individual role of each of the three members of the Orai channel family in Ca(2+)
      influx and mediator release has not been defined in human mast cells. OBJECTIVE:
      To assess whether there might be value in targeting individual Orai family
      members for the inhibition of FcepsilonRI-dependent human lung mast cells (HLMC)
      mediator release. METHODS: We used an adenoviral delivery system to transduce
      HLMCs with shRNAs targeted against Orai1 and Orai2 or with cDNAs directing the
      expression of dominant-negative mutations of the three known Orai channels.
      RESULTS: shRNA-mediated knockdown of Orai1 resulted in a significant reduction of
      approximately 50% in Ca(2+) influx and in the release of beta-hexosaminidase (a
      marker of degranulation) and newly synthesized LTC4 in activated HLMCs. In
      contrast shRNA knockdown of Orai2 resulted in only marginal reductions of Ca(2+)
      influx, degranulation and LTC4 release. Transduced dominant-negative mutants of
      Orai1, -2 and -3 markedly reduced Orai currents and completely inhibited HLMC
      degranulation suggesting that Orai channels form heteromultimers in HLMCs, and
      that Orai channels comprise the dominant Ca(2+) influx pathway following FceRI
      dependent HLMC activation. Inhibition of Orai currents did not alter HLMC
      survival. In addition we observed a significant down-regulation of the level of
      CRACM3 mRNA transcripts together with a small increase in the level of CRACM1 and
      CRACM2 transcripts following a period of sustained HLMC activation. CONCLUSION
      AND CLINICAL RELEVANCE: Orai1 plays an important role in Ca(2+) influx and
      mediator release from HLMCs. Strategies which target Orai1 will effectively
      inhibit FcepsilonRI-dependent HLMC activation, but spare off-target inhibition of
      Orai2 in other cells and body systems.

PMID- 24040357
TI  - Wild orangutan males plan and communicate their travel direction one day in
      advance.
AB  - The ability to plan for the future beyond immediate needs would be adaptive to
      many animal species, but is widely thought to be uniquely human. Although studies
      in captivity have shown that great apes are capable of planning for future needs,
      it is unknown whether and how they use this ability in the wild. Flanged male
      Sumatran orangutans (Pongo abelii) emit long calls, which females use to maintain
      earshot associations with them. We tested whether long calls serve to communicate
      a male's ever-changing predominant travel direction to facilitate maintaining
      these associations. We found that the direction in which a flanged male emits his
      long calls predicts his subsequent travel direction for many hours, and that a
      new call indicates a change in his main travel direction. Long calls given at or
      near the night nest indicate travel direction better than random until late
      afternoon on the next day. These results show that male orangutans make their
      travel plans well in advance and announce them to conspecifics. We suggest that
      such a planning ability is likely to be adaptive for great apes, as well as in
      other taxa. 

PMID- 24040358
TI  - Anti-tumor effect of adipose tissue derived-mesenchymal stem cells expressing
      interferon-beta and treatment with cisplatin in a xenograft mouse model for
      canine melanoma.
AB  - Adipose tissue-derived mesenchymal stem cells (AT-MSCs) are attractive cell
      therapy vehicles for the delivery of anti-tumor molecules into the tumor
      microenvironment. The innate tropism of AT-MSCs for tumors has important
      implications for effective cellular delivery of anti-tumor molecules, including
      cytokines, interferon, and pro-drugs. The present study was designed to determine
      the possibility that the combination of stem cell-based gene therapy with low
      dose cisplatin would improve therapeutic efficacy against canine melanoma. The
      IFN-beta transduced canine AT-MSCs (cAT-MSC-IFN-beta) inhibited the growth of
      LMeC canine melanoma cells in direct and indirect in vitro co-culture systems. In
      animal experiments using BALB/c nude mouse xenografts, which developed by
      injecting LMeC cells, the combination treatment of cAT-MSC-IFN-beta and low-dose
      cisplatin significantly reduced tumor volume compared with the other treatment
      groups. Fluorescent microscopic analysis with a TUNEL (terminal deoxynucleotidyl
      transferase-mediated nick-end labeling) assay of tumor section provided evidence
      for homing of cAT-MSC-IFN-beta to the tumor site and revealed that the
      combination treatment of cAT-MSC-IFN-beta with low-dose cisplatin induced high
      levels of cell apoptosis. These findings may prove useful in further explorations
      of the application of these combined approaches to the treatment of malignant
      melanoma and other tumors. 

PMID- 24040359
TI  - Sexual behavior and condom use among seasonal Dalit migrant laborers to India
      from Far West, Nepal: a qualitative study.
AB  - BACKGROUND: Around 41% of Human Immunodeficiency Virus (HIV) cases in Nepal occur
      in seasonal migrant laborers. Dalit migrant laborers represent the largest
      proportion of reported HIV cases in the Far Western Region (Sudur Pashchimanchal,
      or Far West), Nepal. The study's objectives were to assess sexual behavior,
      condom use status and HIV risk perception among Dalit migrant laborers to India
      from Far West Region, Nepal. METHODS: The study was conducted among Dalit male
      migrant laborers aged 15 years and above who had migrated for at least six months
      of the last two years to India. For the sampling the village development
      committees (VDCs) from Achham, Doti and Kanchanpur districts of Nepal were
      purposively selected. The data were collected in March and April 2011 via ten in
      depth interviews and four focus group discussions and analyzed using content
      analysis. RESULTS: Poor socio-economic status, caste-related discrimination, and
      lack of employment opportunities push large groups of young Dalits to migrate to
      India for employment, where they engage in sex with female sex workers (FSWs).
      The participants described unmarried status, peer influence, alcohol use, low
      priced sex with FSWs and unwillingness to use condoms as common factors of their
      migration experience. Lack of awareness on HIV/AIDS was common among study
      participants. Awareness of HIV/AIDS and faithful, monogamous partnerships are
      reported as factors influencing safer sexual behavior. CONCLUSIONS: Dalits are an
      especially vulnerable population among migrant laborers and may be over
      represented in new HIV infections in Nepal. Comprehensive surveying and health
      promotion programs targeted to this population are urgently needed and potent
      methods of stopping HIV spread.

PMID- 24040361
TI  - Economic conditions at the time of birth and cognitive abilities late in life:
      evidence from ten European countries.
AB  - With ageing populations, it becomes increasingly important to understand the
      determinants of cognitive ability among the elderly. We apply survey data of
      17,070 respondents from ten countries to examine several domains of cognitive
      functioning at ages 60+, and we link them to the macro-economic deviations in the
      year of birth. We find that economic conditions at birth significantly influence
      cognitive functioning late in life in various domains. Recessions negatively
      influence numeracy, verbal fluency, recall abilities, as well as the score on the
      omnibus cognitive indicator. The results are robust; controlling for current
      characteristics does not change effect sizes and significance. We discuss
      possible causal social and biological pathways. 

PMID- 24040360
TI  - Nanoparticle vaccines encompassing the respiratory syncytial virus (RSV) G
      protein CX3C chemokine motif induce robust immunity protecting from challenge and
      disease.
AB  - Nanoparticle vaccines were produced using layer-by-layer fabrication and
      incorporating respiratory syncytial virus (RSV) G protein polypeptides comprising
      the CX3C chemokine motif. BALB/c mice immunized with G protein nanoparticle
      vaccines produced a neutralizing antibody response that inhibited RSV replication
      in the lungs following RSV challenge. ELISPOT analysis showed that G nanoparticle
      vaccinated mice had increased levels of RSV G protein-specific IL-4 and IFN-gamma
      secreting cells compared to controls following RSV challenge. Remarkably, RSV
      challenge of G protein nanoparticle vaccinated mice resulted in increased RSV M2
      specific IL-4 and IFN-gamma secreting T cells, and increased M2-specific H-2Kd
      tetramer positive CD8(+) T cells in the lungs compared to controls. Cell type
      analysis showed vaccination was not associated with increased pulmonary
      eosinophilia following RSV challenge. These results demonstrate that vaccination
      of mice with the RSV G protein nanoparticle vaccines induces a potent
      neutralizing antibody response, increased G protein- and M2-specific T cell
      responses, and a reduction in RSV disease pathogenesis.

PMID- 24040362
TI  - A Rac1/Cdc42 GTPase-specific small molecule inhibitor suppresses growth of
      primary human prostate cancer xenografts and prolongs survival in mice.
AB  - Deregulated Rho GTPases Rac1 and Cdc42 have been discovered in various tumors,
      including prostate and Rac protein expression significantly increases in prostate
      cancer. The Rac and Cdc42 pathways promote the uncontrolled proliferation,
      invasion and metastatic properties of human cancer cells. We synthesized the
      novel compound AZA1 based on structural information of the known Rac1 inhibitor
      NSC23766. In the current study we investigated the effects of inhibition of these
      pathways by AZA1 on prostate tumorigenicity by performing preclinical studies
      using a xenograft mouse model of prostate cancer. In androgen-independent
      prostate cancer cells, AZA1 inhibited both Rac1 and Cdc42 but not RhoA GTPase
      activity in a dose-dependent manner and blocked cellular migration and
      proliferation. Cyclin D1 expression significantly decreased following Rac1/Cdc42
      inhibition in prostate cancer cells. AZA1 treatment also down-regulated PAK and
      AKT activity in prostate cancer cells, associated with induction of the pro
      apoptotic function of BAD by suppression of serine-112 phosphorylation. Daily
      systemic administration of AZA1 for 2 weeks reduced growth of human 22Rv1
      prostate tumor xenografts in mice and improved the survival of tumor-bearing
      animals significantly. These data suggest a role of AZA1 in blocking Rac1/Cdc42
      dependent cell cycle progression, cancer cell migration and increase of cancer
      cell apoptosis involving down-regulation of the AKT and PAK signaling pathway in
      prostate cancer cells. We therefore propose that a small-molecule inhibitor
      therapy targeting Rac1/Cdc42 Rho GTPase signaling pathways may be used as a novel
      treatment for patients with advanced prostate cancer. 

PMID- 24040363
TI  - Cell-cell transmission of VSV-G pseudotyped lentivector particles.
AB  - Many replicating viruses, including HIV-1 and HTLV-1, are efficiently transmitted
      from the cell surface of actively infected cells upon contact with bystander
      cells. In a previous study, we reported the prolonged cell surface retention of
      VSV-G replication-deficient pseudotyped lentivector prior to endocytic entry.
      However, the competing kinetics of cell surface versus dissociation,
      neutralization or direct transfer to other cells have received comparatively
      little attention. Here we demonstrate that the relative efficiency of cell-cell
      surface transmission can outpace "cell-free" transduction at limiting vector
      input. This coincides with the prolonged half-life of cell bound vector but
      occurs, unlike HTLV-1, without evidence for particle aggregation. These studies
      suggest that cell-surface attachment stabilizes particles and alters
      neutralization kinetics. Our experiments provide novel insight into the
      underexplored cell-cell transmission of pseudotyped particles. 

PMID- 24040364
TI  - 53BP1 sensitizes breast cancer cells to 5-fluorouracil.
AB  - Chemoresistance of breast cancer is a worldwide problem for breast cancer and the
      resistance to chemotherapeutic agents frequently led to the subsequent recurrence
      and metastasis. In our previous study, we have found that 53BP1 showed a gradual
      decrease during the progression of breast cancer and loss of 53BP1 was associated
      with metastasis and poor prognosis in breast cancer. Here we aimed to reveal
      whether 53BP1 could sensitize breast cancer to 5-Fu. We found that ectopic
      expression of 53BP1 can significantly sensitize breast cancer cells to 5-Fu while
      knockdown of 53BP1 conferred the resistance. The in vivo experiments confirmed
      that overexpression of 53BP1 in combination with 5-Fu markedly inhibited growth
      of xenotransplanted tumors in nude mice when compared to either agent alone.
      Furthermore, we demonstrated that 53BP1 regulated the sensitivity to 5-Fu through
      thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPYD). The present
      studies provide a new clue that combination of 5-Fu and 53BP1 could be a
      potential novel targeted strategy for overcoming breast cancer chemoresistance. 

PMID- 24040365
TI  - Correlates of light and moderate-to-vigorous objectively measured physical
      activity in four-year-old children.
AB  - BACKGROUND: Correlates of physical activity (PA) are hypothesized to be context
      and behaviour specific, but there is limited evidence of this in young children.
      The aim of the current study is to investigate associations between personal,
      social and environmental factors and objectively measured light and moderate-to
      vigorous PA (LPA and MVPA, respectively) in four-year-old children. METHODS:
      Cross-sectional data were used from the Southampton Women's Survey, a UK
      population-based longitudinal study. Four-year old children (n = 487, 47.0% male)
      had valid PA data assessed using accelerometry (Actiheart) and exposure data
      collected with a validated maternal questionnaire (including data on child
      personality, family demographics, maternal behaviour, rules and restrictions, and
      perceived local environment). Linear regression modelling was used to analyse
      associations with LPA and MVPA separately, interactions with sex were explored.
      RESULTS: LPA minutes were greater in children whose mothers reported more PA (vs.
      inactive: regression coefficient+/-standard error: 6.70+/-2.94 minutes), and
      without other children in the neighbourhood to play with (-6.33+/-2.44). MVPA
      minutes were greater in children with older siblings (vs. none: 5.81+/-2.80) and
      those whose mothers used active transport for short trips (vs. inactive: 6.24+/
      2.95). Children accumulated more MVPA in spring (vs. winter: 9.50+/-4.03) and, in
      boys only, less MVPA with availability of other children in the neighbourhood (
      3.98+/-1.70). DISCUSSION: Young children's LPA and MVPA have differing
      associations with a number of social and environmental variables. Interventions
      targeting PA promotion in young children outside of formal care settings should
      consider including intensity specific factors.

PMID- 24040366
TI  - Conspecific plasticity and invasion: invasive populations of Chinese tallow
      (Triadica sebifera) have performance advantage over native populations only in
      low soil salinity.
AB  - Global climate change may increase biological invasions in part because invasive
      species may have greater phenotypic plasticity than native species. This may be
      especially important for abiotic stresses such as salt inundation related to
      increased hurricane activity or sea level rise. If invasive species indeed have
      greater plasticity, this may reflect genetic differences between populations in
      the native and introduced ranges. Here, we examined plasticity of functional and
      fitness-related traits of Chinese tallow (Triadica sebifera) populations from the
      introduced and native ranges that were grown along a gradient of soil salinity
      (control: 0 ppt; Low: 5 ppt; Medium: 10 ppt; High: 15 ppt) in a greenhouse. We
      used both norm reaction and plasticity index (PIv) to estimate the conspecific
      phenotypic plasticity variation between invasive and native populations. Overall,
      invasive populations had higher phenotypic plasticity of height growth rate
      (HGR), aboveground biomass, stem biomass and specific leaf area (SLA). The
      plasticity Index (PIv) of height growth rate (HGR) and SLA each were higher for
      plants from invasive populations. Absolute performance was always comparable or
      greater for plants from invasive populations versus native populations with the
      greatest differences at low stress levels. Our results were consistent with the
      "Master-of-some" pattern for invasive plants in which the fitness of introduced
      populations was greater in more benign conditions. This suggests that the greater
      conspecific phenotypic plasticity of invasive populations compared to native
      populations may increase invasion success in benign conditions but would not
      provide a potential interspecific competitive advantage in higher salinity soils
      that may occur with global climate change in coastal areas. 

PMID- 24040367
TI  - Commensal Akkermansia muciniphila exacerbates gut inflammation in Salmonella
      Typhimurium-infected gnotobiotic mice.
AB  - Excessive mucin degradation by intestinal bacteria may contribute to inflammatory
      bowel diseases because access of luminal antigens to the intestinal immune system
      is facilitated. This study investigated how the presence of a mucin degrading
      commensal bacterium affects the severity of an intestinal Salmonella enterica
      Typhimurium-induced gut inflammation. Using a gnotobiotic C3H mouse model with a
      background microbiota of eight bacterial species (SIHUMI) the impact of the mucin
      degrading commensal bacterium Akkermansia muciniphila (SIHUMI-A) on inflammatory
      and infectious symptoms caused by S. Typhimurium was investigated. Presence of A.
      muciniphila in S. Typhimurium-infected SIHUMI mice caused significantly increased
      histopathology scores and elevated mRNA levels of IFN-gamma, IP-10, TNF-alpha, IL
      12, IL-17 and IL-6 in cecal and colonic tissue. The increase in pro-inflammatory
      cytokines was accompanied by 10-fold higher S. Typhimurium cell numbers in
      mesenteric lymph nodes of SIHUMI mice associated with A. muciniphila and S.
      Typhimurium (SIHUMI-AS) compared to SIHUMI mice with S. Typhimurium only (SIHUMI
      S). The number of mucin filled goblet cells was 2- to 3-fold lower in cecal
      tissue of SIHUMI-AS mice compared to SIHUMI-S, SIHUMI-A or SIHUMI mice. Reduced
      goblet cell numbers significantly correlated with increased IFN-gamma mRNA levels
      (r(2) = -0.86, ***P<0.001) in all infected mice. In addition, loss of cecal mucin
      sulphation was observed in SIHUMI mice containing both A. muciniphila and S.
      Typhimurium compared to other mouse groups. Concomitant presence of A.
      muciniphila and S. Typhimurium resulted in a drastic change in microbiota
      composition of SIHUMI mice: the proportion of B. thetaiotaomicron in SIHUMI-AS
      mice was 0.02% of total bacteria compared to 78%-88% in the other mouse groups
      and the proportion of S. Typhimurium was 94% in SIHUMI-AS mice but only 2.2% in
      the SIHUMI-S mice. These results indicate that A. muciniphila exacerbates S.
      Typhimurium-induced intestinal inflammation by its ability to disturb host mucus
      homeostasis.

PMID- 24040368
TI  - Isolation associated aggression--a consequence of recovery from defeat in a
      territorial animal.
AB  - Population density has profound influences on the physiology and behaviour of
      many animal species. Social isolation is generally reported to lead to increased
      aggressiveness, while grouping lowers it. We evaluated the effects of varying
      degrees of isolation and grouping on aggression in a territorial insect, the
      Mediterranean field cricket, Gryllus bimaculatus. Substantiating early
      observations, we show that dyadic contests between weight-matched, adult male
      crickets taken from groups rarely escalate beyond threat displays, whereas
      interactions between pairs of previously isolated crickets typically escalate to
      physical fights lasting several seconds. No significant differences were found
      between 1, 2 and 6-day isolates, or between individuals grouped for a few hours
      or lifelong. Unexpectedly, crickets grouped in immediate proximity within
      individual mesh cages that precluded fighting while permitting visual, olfactory
      and mechanical, antennal contact, were as aggressive as free isolates. This
      suggests that reduced aggression of grouped animals may be an acquired result of
      fighting. Supporting this notion, isolated crickets initially engage in vigorous
      fights when first grouped, but fighting intensity and duration rapidly decline to
      the level of life-long grouped crickets within only 10 min. Furthermore, grouped
      crickets become as aggressive as life-long isolates after only 3 hours of
      isolation, and on the same time course required for crickets to regain their
      aggressiveness after social defeat. We conclude that the reduced aggressiveness
      of grouped crickets is a manifestation of the loser effect resulting from social
      subjugation, while isolation allows recovery to a state of heightened
      aggressiveness, which in crickets can be considered as the default condition.
      Given the widespread occurrence of the loser effect in the Animal Kingdom, many
      effects generally attributed to social isolation are likely to be a consequence
      of recovery from social subjugation.

PMID- 24040369
TI  - Bone marrow injury induced via oxidative stress in mice by inhalation exposure to
      formaldehyde.
AB  - OBJECTIVE: Formaldehyde, a ubiquitous environmental pollutant has been classified
      as a human leukemogen. However, toxicity of formaldehyde in bone marrow, the
      target site of leukemia induction, is still poorly understood.
      METHODOLOGY/PRINCIPAL FINDINGS: To investigate bone marrow toxicity (bone marrow
      pathology, hematotoxicity) and underlying mechanisms (oxidative stress,
      inflammation, apoptosis) in formaldehyde-exposed mice. Male Balb/c mice were
      exposed to formaldehyde (0, 0.5, and 3.0 mg/m(3)) by nose-only inhalation for 8
      hours/day, over a two week period designed to simulate a factory work schedule,
      with an exposure-free "weekend" on days 6 and 7, and were sacrificed on the
      morning of day 13. Counts of white blood cells, red blood cells and lymphocytes
      were significantly (p<0.05) decreased at 0.5 mg/m(3) (43%, 7%, and 39%,
      respectively) and 3.0 mg/m(3) (52%, 27%, and 43%, respectively) formaldehyde
      exposure, while platelet counts were significantly increased by 109% (0.5
      mg/m(3)) and 67% (3.0 mg/m(3)). Biomarkers of oxidative stress (reactive oxygen
      species, glutathione depletion, cytochrome P450 1A1 and glutathione s-transferase
      theta 1 expression), inflammation (nuclear factor kappa-B, tomour necrosis factor
      alpha, interleukin-1 beta), and apoptosis (activity of cysteine-aspartic acid
      protease 3) in bone marrow tissues were induced at one or both formaldehyde doses
      mentioned above. CONCLUSIONS/SIGNIFICANCE: Exposure of mice to formaldehyde by
      inhalation induced bone marrow toxicity, and that oxidative stress, inflammation
      and the consequential apoptosis jointly constitute potential mechanisms of such
      induced toxicity.

PMID- 24040370
TI  - Electric field driven torque in ATP synthase.
AB  - FO-ATP synthase (FO) is a rotary motor that converts potential energy from ions,
      usually protons, moving from high- to low-potential sides of a membrane into
      torque and rotary motion. Here we propose a mechanism whereby electric fields
      emanating from the proton entry and exit channels act on asymmetric charge
      distributions in the c-ring, due to protonated and deprotonated sites, and drive
      it to rotate. The model predicts a scaling between time-averaged torque and
      proton motive force, which can be hindered by mutations that adversely affect the
      channels. The torque created by the c-ring of FO drives the gamma-subunit to
      rotate within the ATP-producing complex (F1) overcoming, with the aid of thermal
      fluctuations, an opposing torque that rises and falls with angular position.
      Using the analogy with thermal Brownian motion of a particle in a tilted
      washboard potential, we compute ATP production rates vs. proton motive force. The
      latter shows a minimum, needed to drive ATP production, which scales inversely
      with the number of proton binding sites on the c-ring. 

PMID- 24040371
TI  - Impaired hypothalamic mTOR activation in the adult rat offspring born to mothers
      fed a low-protein diet.
AB  - Several epidemiological and experimental studies have clearly established that
      maternal malnutrition induces a high risk of developing obesity and related
      metabolic diseases in the offspring. To determine if altered nutrient sensing
      might underlie this enhanced disease susceptibility, here we examined the effects
      of perinatal protein restriction on the activation of the nutrient sensor mTOR in
      response to acute variations in the nutritional status of the organism. Female
      Wistar rats were fed isocaloric diets containing either 17% protein (control) or
      8% protein (PR) throughout pregnancy and lactation. At weaning offspring received
      standard chow and at 4 months of age the effects of fasting or fasting plus re
      feeding on the phosphorylation levels of mTOR and its downstream target S6
      ribosomal protein (rpS6) in the hypothalamus were assessed by immuno-fluorescence
      and western blot. Under ad libitum feeding conditions, PR rats exhibited
      decreased mTOR and rpS6 phosphorylation in the arcuate (ARC) and ventromedial
      (VMH) hypothalamic nuclei. Moreover, the phosphorylation of mTOR and rpS6 in
      these hypothalamic nuclei decreased with fasting in control but not in PR
      animals. Conversely, PR animals exhibited enhanced number of pmTOR imunostained
      cells in the paraventricular nucleus (PVN) and fasting decreased the activation
      of mTOR in the PVN of malnourished but not of control rats. These alterations
      occurred at a developmental stage at which perinatally-undernourished animals do
      not show yet obesity or glucose intolerance. Collectively, our observations
      suggest that altered hypothalamic nutrient sensing in response to an inadequate
      foetal and neonatal energetic environment is one of the basic mechanisms of the
      developmental programming of metabolic disorders and might play a causing role in
      the development of the metabolic syndrome induced by malnutrition during early
      life. 

PMID- 24040372
TI  - Topical drug delivery in chronic rhinosinusitis patients before and after sinus
      surgery using pulsating aerosols.
AB  - OBJECTIVES: Chronic rhinosinusitis (CRS) is a common chronic disease of the upper
      airways and has considerable impact on quality of life. Topical delivery of drugs
      to the paranasal sinuses is challenging, therefore the rate of surgery is high.
      This study investigates the delivery efficiency of a pulsating aerosol in
      comparison to a nasal pump spray to the sinuses and the nose in healthy
      volunteers and in CRS patients before and after sinus surgery. METHODS: (99m)Tc
      DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal
      polyps before and after sinus surgery. In addition, pulsating aerosols were
      studied in comparison to nasal pump sprays in eleven healthy volunteers. Total
      nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung
      penetration were assessed by anterior and lateral planar gamma camera imaging.
      RESULTS: In healthy volunteers nasal pump sprays resulted in 100% nasal, non
      significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/
      8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal
      dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total
      nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus
      surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus
      deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in
      healthy volunteers nor in CRS patients there was significant dose in the frontal
      sinuses. CONCLUSION: In contrast to nasal pump sprays, pulsating aerosols can
      deliver significant doses into posterior nasal spaces and paranasal sinuses,
      providing alternative therapy options before and after sinus surgery. Patients
      with chronic lung diseases based on clearance dysfunction may also benefit from
      pulsating aerosols, since these diseases also manifest in the upper airways.

PMID- 24040373
TI  - Serum phosphate as a risk factor for cardiovascular events in people with and
      without chronic kidney disease: a large community based cohort study.
AB  - BACKGROUND: Serum phosphate is a known risk factor for cardiovascular events and
      mortality in people with chronic kidney disease (CKD), however data on the
      association of these outcomes with serum phosphate in the general population are
      scarce. We investigate this relationship in people with and without CKD in a
      large community-based population. METHODS: Three groups from an adult cohort of
      the Quality Improvement in Chronic Kidney Disease (QICKD) cluster randomised
      trial (ISRCTN56023731) were followed over a period of 2.5 years: people with
      normal renal function (N = 24,184), people with CKD stages 1-2 (N = 20,356), and
      people with CKD stages 3-5 (N = 13,292). We used a multilevel logistic regression
      model to determine the association between serum phosphate, in these groups, and
      a composite outcome of all-cause mortality, cardiovascular events, and advanced
      coronary artery disease. We adjusted for known cardiovascular risk factors.
      FINDINGS: Higher phosphate levels were found to correlate with increased
      cardiovascular risk. In people with normal renal function and CKD stages 1-2,
      Phosphate levels between 1.25 and 1.50 mmol/l were associated with increased
      cardiovascular events; odds ratio (OR) 1.36 (95% CI 1.06-1.74; p = 0.016) in
      people with normal renal function and OR 1.40 (95% CI 1.09-1.81; p = 0.010) in
      people with CKD stages 1-2. Hypophosphatemia (<0.75 mmol/l) was associated with
      fewer cardiovascular events in people with normal renal function; OR 0.59 (95% CI
      0.36-0.97; p = 0.049). In people with CKD stages 3-5, hyperphosphatemia (>1.50
      mmol/l) was associated with increased cardiovascular risk; OR 2.34 (95% CI 1.64
      3.32; p<0.001). Other phosphate ranges were not found to have a significant
      impact on cardiovascular events in people with CKD stages 3-5. CONCLUSIONS: Serum
      phosphate is associated with cardiovascular events in people with and without
      CKD. Further research is required to determine the mechanisms underlying these
      associations.

PMID- 24040374
TI  - Effects of dietary cooked navy bean on the fecal microbiome of healthy companion
      dogs.
AB  - BACKGROUND: Cooked bean powders are a promising novel protein and fiber source
      for dogs, which have demonstrated potential to alter microbial composition and
      function for chronic disease control and prevention. This study aimed to
      determine the impact of cooked navy bean powder fed as a staple food ingredient
      on the fecal microbiome of healthy adult pet dogs. METHODOLOGY/PRINCIPAL
      FINDINGS: Fecal samples from healthy dogs prior to dietary control and after 4 wk
      of dietary treatment with macro- and micronutrient matched diets containing
      either 0 or 25% cooked navy beans (n = 11 and n = 10, respectively) were analyzed
      by 454-pyrosequencing of the 16S rRNA gene. There were few differences between
      dogs fed the control and navy bean diets after 4 wk of treatment. These data
      indicate that there were no major effects of navy bean inclusion on microbial
      populations. However, significant differences due to dietary intervention onto
      both research diets were observed (i.e., microbial populations at baseline versus
      4 wk of intervention with 0 or 25% navy bean diets). After 4 wk of dietary
      intervention on either control or navy bean diet, the Phylum Firmicutes was
      increased and the Phyla Actinobacteria and Fusobacteria were decreased compared
      to baseline. CONCLUSIONS: No negative alterations of microbial populations
      occurred following cooked navy bean intake in dogs, indicating that bean powders
      may be a viable protein and fiber source for commercial pet foods. The highly
      variable microbial populations observed in these healthy adult pet dogs at
      baseline is one potential reason for the difficulty to detect alterations in
      microbial populations following dietary changes. Given the potential
      physiological benefits of bean intake in humans and dogs, further evaluation of
      the impacts of cooked navy bean intake on fecal microbial populations with higher
      power or more sensitive methods are warranted.

PMID- 24040375
TI  - Health risk assessment of heavy metals in rice to the population in Zhejiang,
      China.
AB  - Environmental pollution with toxic heavy metals can lead to the possible
      contamination of the rice. Selected metals (As, Cd, Hg and Pb) and their
      accumulation in rice collected from Zhejiang, China were analyzed to evaluate the
      potential health risk to the local adults and children. The mean levels found in
      rice were as follows: As, 0.080 mg/kg; Cd, 0.037 mg/kg; Hg, 0.005 mg/kg; Pb,
      0.060 mg/kg. The estimated daily intakes (EDIs) were calculated in combination of
      the rice consumption data. The mean intakes of As, Cd, Hg and Pb through rice
      were estimated to be 0.49, 0.23, 0.03 and 0.37 ug/kg bw/day for adults, and 0.34,
      0.29, 0.04 and 0.47 ug/kg bw/day for children. The 97.5th percentile (P97.5)
      daily intakes of As, Cd, Hg and Pb were 1.02, 0.64, 0.37 and 1.26 ug/kg bw/day
      for adults, and 0.63, 0.83, 0.47 and 1.63 ug/kg bw/day for children. The risk
      assessment in mean levels showed that health risk associated with these elements
      through consumption of rice was absent. However, estimates in P97.5 level of Cd
      and Pb for children, and Hg for adults have exceeded the respective safe limits. 

PMID- 24040376
TI  - Alteration of intestinal microbiota in mice orally administered with salmon
      cartilage proteoglycan, a prophylactic agent.
AB  - Proteoglycan (PG) extracted from salmon nasal cartilage has potential to be a
      prophylactic agent. Daily oral administration of the PG attenuates systemic
      inflammatory response in the experimental mouse models. In this study, we applied
      the culture-independent approach to investigate an alteration of intestinal
      microbiota composition in PG-administered mice. The results indicated that the
      population level of bacilli increased in the small and large intestine upon PG
      administration. On the other hand, the population level of clostridia decreased
      in the large intestine. The proportion of bacteria that are able to ferment
      saccharides and produce short-chain fatty acids increased in the small intestine
      and decreased in the large intestine. Importantly, population level of probiotic
      lactobacilli and bacteria exhibiting the immunomodulatory effect increased in the
      PG-administered mice. In addition, several disease-associated bacteria decreased
      upon PG administration. These results provided an understanding of the specific
      role of PG involved in host immune modulation and supported our hypothesis that
      daily oral administration of PG improves the overall balance in composition of
      the intestinal microbial community. 

PMID- 24040377
TI  - An assessment of health behavior peer effects in Peking University dormitories: a
      randomized cluster-assignment design for interference.
AB  - BACKGROUND: Relatively little is known about the peer influence in health
      behaviors within university dormitory rooms. Moreover, in China, the problem of
      unhealthy behaviors among university students has not yet been sufficiently
      recognized. We thus investigated health behavior peer influence in Peking
      University dormitories utilizing a randomized cluster-assignment design. METHODS:
      STUDY DESIGN: Cross-sectional in-dormitory survey. STUDY POPULATION: Current
      students from Peking University Health Science Center from April to June, 2009.
      MEASUREMENT: Self-reported questionnaire on health behaviors: physical activity
      (including bicycling), dietary intake and tobacco use. RESULTS: Use of bicycle,
      moderate-intensity exercise, frequency of sweet food and soybean milk intake,
      frequency of roasted/baked/toasted food intake were behaviors significantly or
      marginally significantly affected by peer influence. CONCLUSION: Health behavior
      peer effects exist within dormitory rooms among university students. This could
      provide guidance on room assignment, or inform intervention programs. Examining
      these may demand attention from university administrators and policy makers.

PMID- 24040379
TI  - Glycan structures contain information for the spatial arrangement of
      glycoproteins in the plasma membrane.
AB  - Glycoconjugates at the cell surface are crucial for cells to communicate with
      each other and the extracellular microenvironment. While it is generally accepted
      that glycans are vectorial biopolymers, their information content is unclear.
      This report provides evidence that distinct N-glycan structures influence the
      spatial arrangement of two integral membrane glycoproteins, Kv3.1 and E-cadherin,
      at the adherent membrane which in turn alter cellular properties. Distinct N
      glycan structures were generated by heterologous expression of these
      glycoproteins in parental and glycosylation mutant Chinese hamster ovary cell
      lines. Unlike the N-linked glycans, the O-linked glycans of the mutant cell lines
      are similar to those of the parental cell line. Western and lectin blots of total
      membranes and GFP immunopurified samples, combined with glycosidase digestion
      reactions, were employed to verify the glycoproteins had predominantly complex,
      oligomannose, and bisecting type N-glycans from Pro(-)5, Lec1, and Lec10B cell
      lines, respectively. Based on total internal reflection fluorescence and
      differential interference contrast microscopy techniques, and cellular assays of
      live parental and glycosylation mutant CHO cells, we propose that glycoproteins
      with complex, oligomannose or bisecting type N-glycans relay information for
      localization of glycoproteins to various regions of the plasma membrane in both a
      glycan-specific and protein-specific manner, and furthermore cell-cell
      interactions are required for deciphering much of this information. These
      distinct spatial arrangements also impact cell adhesion and migration. Our
      findings provide direct evidence that N-glycan structures of glycoproteins
      contribute significantly to the information content of cells. 

PMID- 24040378
TI  - Differentially expressed microRNAs in chondrocytes from distinct regions of
      developing human cartilage.
AB  - There is compelling in vivo evidence from reports on human genetic mutations and
      transgenic mice that some microRNAs (miRNAs) play an important functional role in
      regulating skeletal development and growth. A number of published in vitro
      studies also point toward a role for miRNAs in controlling chondrocyte gene
      expression and differentiation. However, information on miRNAs that may regulate
      a specific phase of chondrocyte differentiation (i.e. production of progenitor,
      differentiated or hypertrophic chondrocytes) is lacking. To attempt to bridge
      this knowledge gap, we have investigated miRNA expression patterns in human
      embryonic cartilage tissue. Specifically, a developmental time point was
      selected, prior to endochondral ossification in the embryonic limb, to permit
      analysis of three distinct populations of chondrocytes. The location of
      chondroprogenitor cells, differentiated chondrocytes and hypertrophic
      chondrocytes in gestational day 54-56 human embryonic limb tissue sections was
      confirmed both histologically and by specific collagen expression patterns. Laser
      capture microdissection was utilized to separate the three chondrocyte
      populations and a miRNA profiling study was carried out using TaqMan(r)
      OpenArray(r) Human MicroRNA Panels (Applied Biosystems(r)). Here we report on
      abundantly expressed miRNAs in human embryonic cartilage tissue and, more
      importantly, we have identified miRNAs that are significantly differentially
      expressed between precursor, differentiated and hypertrophic chondrocytes by 2
      fold or more. Some of the miRNAs identified in this study have been described in
      other aspects of cartilage or bone biology, while others have not yet been
      reported in chondrocytes. Finally, a bioinformatics approach was applied to begin
      to decipher developmental cellular pathways that may be regulated by groups of
      differentially expressed miRNAs during distinct stages of chondrogenesis. Data
      obtained from this work will serve as an important resource of information for
      the field of cartilage biology and will enhance our understanding of miRNA-driven
      mechanisms regulating cartilage and endochondral bone development, regeneration
      and repair. 

PMID- 24040380
TI  - Inactivation of norovirus on dry copper alloy surfaces.
AB  - Noroviruses (family Caliciviridae) are the primary cause of viral gastroenteritis
      worldwide. The virus is highly infectious and touching contaminated surfaces can
      contribute to infection spread. Although the virus was identified over 40 years
      ago the lack of methods to assess infectivity has hampered the study of the human
      pathogen. Recently the murine virus, MNV-1, has successfully been used as a close
      surrogate. Copper alloys have previously been shown to be effective antimicrobial
      surfaces against a range of bacteria and fungi. We now report rapid inactivation
      of murine norovirus on alloys, containing over 60% copper, at room temperature
      but no reduction of infectivity on stainless steel dry surfaces in simulated wet
      fomite and dry touch contamination. The rate of inactivation was initially very
      rapid and proportional to copper content of alloy tested. Viral inactivation was
      not as rapid on brass as previously observed for bacteria but copper-nickel alloy
      was very effective. The use of chelators and quenchers of reactive oxygen species
      (ROS) determined that Cu(II) and especially Cu(I) ions are still the primary
      effectors of toxicity but quenching superoxide and hydroxyl radicals did not
      confer protection. This suggests Fenton generation of ROS is not important for
      the inactivation mechanism. One of the targets of copper toxicity was the viral
      genome and a reduced copy number of the gene for a viral encoded protein, VPg
      (viral-protein-genome-linked), which is essential for infectivity, was observed
      following contact with copper and brass dry surfaces. The use of antimicrobial
      surfaces containing copper in high risk closed environments such as cruise ships
      and care facilities could help to reduce the spread of this highly infectious and
      costly pathogen. 

PMID- 24040381
TI  - Foster dams rear fighters: strain-specific effects of within-strain fostering on
      aggressive behavior in male mice.
AB  - It is well known that genes and environment interact to produce behavioral
      phenotypes. One environmental factor with long-term effects on gene transcription
      and behavior is maternal care. A classic paradigm for examining maternal care and
      genetic interactions is to foster pups of one genetic strain to dams of a
      different strain ("between-strain fostering"). In addition, fostering to a dam of
      the same strain ("within-strain fostering") is used to reduce indirect effects,
      via behavioral changes in the dams, of gestation treatments on offspring. Using
      within-and between-strain fostering we examined the contributions of
      genetics/prenatal environment, maternal care, and the effects of fostering per
      se, on adult aggressive behavior in two inbred mouse strains, C57BL/6J (B6) and
      DBA/2J (DBA). We hypothesized that males reared by dams of the more aggressive
      DBA strain would attack intruders faster than those reared by B6 dams.
      Surprisingly, we found that both methods of fostering enhanced aggressive
      behavior, but only in B6 mice. Since all the B6 offspring are genetically
      identical, we asked if maternal behavior of B6 dams was affected by the
      relatedness of their pups. In fact, B6 dams caring for foster B6 pups displayed
      significantly reduced maternal behaviors. Finally, we measured vasopressin and
      corticotrophin releasing hormone mRNA in the amygdalae of adult B6 males reared
      by foster or biological dams. Both genes correlated with aggressive behavior in
      within-strain fostered B6 mice, but not in mice reared by their biological dams.
      In sum, we have demonstrated in inbred laboratory mice, that dams behave
      differently when rearing their own newborn pups versus pups from another dam of
      the same strain. These differences in maternal care affect aggression in the male
      offspring and transcription of Avp and Crh in the brain. It is likely that
      rearing by foster dams has additional effects and implications for other species.

PMID- 24040382
TI  - Patterns of linkage disequilibrium of LRRK2 across different races: implications
      for genetic association studies.
AB  - Genome Wide Association Studies (GWASs) have identified trait-associated
      polymorphisms via a hypothesis-free approach. However, it is challenging when
      attempting to reproduce GWAS findings in different populations as it
      fundamentally relies on the similar patterns of linkage disequilibrium (LD)
      between the unknown causal variants and the genotyped single nucleotide
      polymorphisms (SNPs). To address this potential limitation, we examined the
      regional LD pattern of leucine-rich repeat kinase 2 (LRRK2) gene, which is
      responsible for both autosomal dominant and sporadic Parkinson's disease (PD), in
      Caucasians (CEU), Japanese (JPT) and Chinese (CHB) from HapMap and Chinese (CHS),
      Malays (MAS) and Indians (INS) from the Singapore Genome Variation Project (SGVP)
      utilizing the traditional heatmaps and targeted analysis of LRRK2 gene via Monte
      Carlo simulation through varLD scores of these ethnic groups. Both heatmaps and
      targeted analysis showed that LD pattern of JPT was different from that of INS
      (P=0.0001); while LD pattern of CEU was different from that in Asian except for
      INS (all P=0.0001). Our study suggests that there is a higher chance to detect
      associations between PD and those trait-associated SNPs of LRRK2 gene found in
      Caucasian studies in INS, while those found in Japanese studies are likely to be
      better replicated among CHB. 

PMID- 24040383
TI  - Amyloid-beta and APP deficiencies cause severe cerebrovascular defects: important
      work for an old villain.
AB  - Alzheimer's disease (AD) is marked by neuritic plaques that contain insoluble
      deposits of amyloid-beta (Abeta), yet the physiological function of this peptide
      has remained unclear for more than two decades. Using genetics and pharmacology
      we have established that Abeta plays an important role in regulating capillary
      bed density within the brain, a function that is distinct from other cleavage
      products of amyloid precursor protein (APP). APP-deficient zebrafish had fewer
      cerebrovascular branches and shorter vessels in the hindbrain than wild-type
      embryos; this phenotype was rescued by treatment with human Abeta peptide, but
      not a smaller APP fragment called p3. Similar vascular defects were seen in
      zebrafish treated with a beta-secretase inhibitor (BSI) that blocked endogenous
      Abeta production. BSI-induced vascular defects were also improved by treatment
      with human Abeta, but not p3. Our results demonstrate a direct correlation
      between extracellular levels of Abeta and cerebrovascular density in the
      developing hindbrain. These findings may be relevant to AD etiology where high
      levels of Abeta in the brain parenchyma precede the development of neuritic
      plaques and dense aberrantly-branched blood vessel networks that appear between
      them. The ability of Abeta to modify blood vessels may coordinate capillary
      density with local metabolic activity, which could explain the evolutionary
      conservation of this peptide from lobe-finned fish to man. 

PMID- 24040384
TI  - Engineering yeast hexokinase 2 for improved tolerance toward xylose-induced
      inactivation.
AB  - Hexokinase 2 (Hxk2p) from Saccharomyces cerevisiae is a bi-functional enzyme
      being both a catalyst and an important regulator in the glucose repression
      signal. In the presence of xylose Hxk2p is irreversibly inactivated through an
      autophosphorylation mechanism, affecting all functions. Consequently, the
      regulation of genes involved in sugar transport and fermentative metabolism is
      impaired. The aim of the study was to obtain new Hxk2p-variants, immune to the
      autophosphorylation, which potentially can restore the repressive capability
      closer to its nominal level. In this study we constructed the first condensed,
      rationally designed combinatorial library targeting the active-site in Hxk2p. We
      combined protein engineering and genetic engineering for efficient screening and
      identified a variant with Phe159 changed to tyrosine. This variant had 64% higher
      catalytic activity in the presence of xylose compared to the wild-type and is
      expected to be a key component for increasing the productivity of recombinant
      xylose-fermenting strains for bioethanol production from lignocellulosic
      feedstocks. 

PMID- 24040385
TI  - Abnormal functional connectivity of amygdala in late-onset depression was
      associated with cognitive deficits.
AB  - BACKGROUND: Major depressive disorder (MDD) is associated with decreased function
      of cortico-limbic circuits, which play important roles in the pathogenesis of
      MDD. Abnormal functional connectivity (FC) with the amygdala, which is involved
      in cortico-limbic circuits, has also been observed in MDD. However, little is
      known about connectivity alterations in late-onset depression (LOD) or whether
      disrupted connectivity is correlated with cognitive impairment in LOD. METHODS
      AND RESULTS: A total of twenty-two LOD patients and twenty-two matched healthy
      controls (HC) underwent neuropsychological tests and resting state functional
      magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) and FC with
      bilateral amygdala seeds were used to analyze blood oxygen level-dependent fMRI
      data between two groups. Compared with HC, LOD patients showed decreased ReHo in
      the right middle frontal gyrus and left superior frontal gyrus. In the LOD group,
      the left amygdala had decreased FC with the right middle frontal gyrus and the
      left superior frontal gyrus in the amygdala positive network, and it had
      increased FC with the right post-central gyrus in the amygdala negative network.
      However, significantly reduced FC with the right amygdala was observed in the
      right middle occipital gyrus in the amygdala negative network. Further
      correlative analyses revealed that decreased FC between the amygdala and the
      right middle occipital gyrus was negatively correlated with the verbal fluency
      test (VFT, r = -0.485, P = 0.022) and the digit span test (DST, r = -0.561, P =
      0.007). CONCLUSIONS: Our findings of reduced activity of the prefrontal gyrus and
      abnormal FC with the bilateral amygdala may be key markers of cognitive
      dysfunction in LOD patients.

PMID- 24040386
TI  - Fish oil has beneficial effects on allergen-induced airway inflammation and
      hyperreactivity in mice.
AB  - BACKGROUND: Fish oil (FO) is rich in n-3 polyunsaturated fatty acids (PUFA),
      which have been suggested to be anti-inflammatory and are associated with
      improvement of several inflammatory diseases. In this study, we investigated the
      influence of FO on allergen-induced lung inflammation and airway hyperreactivity
      in mice. METHODS: Male A/J mice were fed either a standard-chow (SC) or a FO diet
      (FO) for 8 weeks. After 4 weeks, each group was further randomized for ovalbumin
      (SC-OVA and FO-OVA) or saline (SC-SAL and FO-SAL) challenge. Resistance and
      elastance were measured at baseline and after aerosolized methacholine, 24h after
      the last challenge. Bronchoalveolar lavage (BAL) was performed for leukocyte
      counts. Lung tissue mucus deposition, peribronchiolar matrix deposition and
      eosinophil infiltration were quantified. Serum immunoglobulin E (IgE) and IgG1
      (ref 2.2), lung IL-4, IL-5, IL-10, IL-13, IL-17, INFgamma and eotaxin-1 and 2
      were detected by ELISA and nuclear factor kappa B (NFkappaB), GATA-3 and
      peroxisome proliferator-activated receptor gamma (PPARgamma) expression was
      measured by Western blot. RESULTS: Levels of serum IgE and IgG1 were
      significantly higher in OVA sensitized mice. OVA challenge resulted in increased
      eosinophil infiltration, increased inflammatory cytokine production,
      peribronchiolar matrix and mucus deposition and airway hyperreactivity to
      aerosolized methacholine. Elevated lung NFkappaB and GATA-3 expression was noted
      in OVA-challenged mice. These changes were attenuated in mice fed with FO diet.
      Higher PPARgamma expression was also detected in the lungs from the FO-fed
      groups. CONCLUSION: Our results demonstrate that FO intake attenuated classical
      asthma features by suppressing the systemic sensitization, thus providing
      evidence that FO might be a prophylactic alternative for asthma prevention.

PMID- 24040388
TI  - Strong stability and host specific bacterial community in faeces of ponies.
AB  - The horse, as a hindgut fermenter, is reliant on its intestinal bacterial
      population for efficient diet utilisation. However, sudden disturbance of this
      population can result in severe colic or laminitis, both of which may require
      euthanasia. This study therefore aimed to determine the temporal stability of the
      bacterial population of faecal samples from six ponies maintained on a formulated
      high fibre diet. Bacterial 16S rRNA terminal restriction fragment length
      polymorphism (TRFLP) analyses of 10 faecal samples collected from 6 ponies at
      regular intervals over 72 hour trial periods identified a significant pony
      specific profile (P<0.001) with strong stability. Within each pony, a
      significantly different population was found after 11 weeks on the same diet
      (P<0.001) and with greater intra-individual similarity. Total short chain fatty
      acid (SCFA) concentration increased in all ponies, but other changes (such as
      bacterial population diversity measures, individual major SCFA concentration)
      were significant and dependent on the individual. This study is the first to
      report the extent of stability of microbes resident in the intestinal tract as
      represented with such depth and frequency of faecal sampling. In doing so, this
      provides a baseline from which future trials can be planned and the extent to
      which results may be interpreted. 

PMID- 24040387
TI  - Penetration of fosfomycin into IPEC-J2 cells in the presence or absence of
      deoxynivalenol.
AB  - Fosfomycin (FOS) is an antibiotic used in pig farms for treatment and prevention
      of infections caused by resistant bacteria during the post-weaning period.
      Antibiotics and non-toxic concentrations of mycotoxins, such as deoxynivalenol
      (DON) are frequently found in the diet of animals. These compounds can establish
      interactions in the intestinal tract, which could affect and/or modify the
      penetration of FOS to enterocytes. The aim of this study was to determine the
      penetration of FOS into IPECJ-2 cells, a cell line derived from the small
      intestine of piglets, in the presence and absence of DON. The results from this
      study showed that there was statistically significant difference in the
      intracellular concentration of FOS between cells incubated with 580 ug/ml FOS and
      cells incubated with 580 ug/ml FOS and 1 ug/ml DON. The Cmax of the intracellular
      antibiotic in the culture plates incubated with FOS in absence of DON was 45.81
      ug/ml with a tmax of 4 h. When IPEC-2 cells were incubated with FOS and DON the
      Cmax was 20.06 ug/ml and the tmax was 30 min. It is concluded that the non-toxic
      concentration of DON on IPEC-J2 cells after short-term exposure, interferes with
      the pharmacokinetics of the antibiotic. 

PMID- 24040389
TI  - IBC CARe microarray allelic population prevalences in an American Indian
      population.
AB  - BACKGROUND: The prevalence of variant alleles among single nucleotide
      polymorphisms (SNPs) is not well known for many minority populations. These
      population allele frequencies (PAFs) are necessary to guide genetic epidemiology
      studies and to understand the population specific contribution of these variants
      to disease risk. Large differences in PAF among certain functional groups of
      genes could also indicate possible selection pressure or founder effects of
      interest. The 50K SNP, custom genotyping microarray (CARe) was developed,
      focusing on about 2,000 candidate genes and pathways with demonstrated
      pathophysiologic influence on cardiovascular disease (CVD). METHODS: The CARe
      microarray was used to genotype 216 unaffected controls in a study of pre
      eclampsia among a Northern Plains, American Indian tribe. The allelic prevalences
      of 34,240 SNPs suitable for analysis, were determined and compared with
      corresponding HapMap prevalences for the Caucasian population. Further analysis
      was conducted to compare the frequency of statistically different prevalences
      among functionally related SNPs, as determined by the DAVID Bioinformatics
      Resource. RESULTS: Of the SNPs with PAFs in both datasets, 9.8%,37.2% and 47.1%
      showed allele frequencies among the American Indian population greater than, less
      than and either greater or less than (respectively) the HapMap Caucasian
      population. The 2,547 genes were divided into 53 functional groups using the
      highest stringency criteria. While none of these groups reached the Bonferroni
      corrected p value of 0.00094, there were 7 of these 53 groups with significantly
      more or less differing PAFs, each with a probability of less than 0.05 and an
      overall probability of 0.0046. CONCLUSION: In comparison to the HapMap Caucasian
      population, there are substantial differences in the prevalence among an American
      Indian community of SNPs related to CVD. Certain functional groups of genes and
      related SNPs show possible evidence of selection pressure or founder effects.

PMID- 24040390
TI  - Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in
      the R6/2 mouse model of Huntington's disease.
AB  - The reduction of pre-enkephalin (pENK) mRNA expression might be an early sign of
      striatal neuronal dysfunction in Huntington's disease (HD), due to mutated
      huntingtin protein. Indeed, striatopallidal (pENK-containing) neurodegeneration
      occurs at earlier stage of the disease, compare to the loss of striatonigral
      neurons. However, no data are available about the functional role of striatal
      pENK in HD. According to the neuroprotective properties of opioids that have been
      recognized recently, the objective of this study was to investigate whether
      striatal overexpression of pENK at early stage of HD can improve motor
      dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse
      model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2)
      containing green fluorescence protein (GFP)-pENK was injected bilaterally in the
      striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal
      injection of rAAV2-GFP was used as a control. Different behavioral tests were
      carried out before and/or after striatal injections of rAAV2. The animals were
      euthanized at 10 weeks old. Our results demonstrate that striatal overexpression
      of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying
      the onset of decline in muscular force; reduction of clasping; improvement of
      fast motor activity, short-term memory and recognition; as well as normalization
      of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice
      having received rAAV2-GFP-pENK associated with upregulation of striatal pENK
      mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus
      and substantia nigra; as well as the slight increase in the number of striatal
      neurons compared with other groups of R6/2. Accordingly, we suggest that at early
      stage of HD upregulation of striatal enkephalin might play a key role at
      attenuating illness symptoms. 

PMID- 24040391
TI  - The anti-tumor effect of HDAC inhibition in a human pancreas cancer model is
      significantly improved by the simultaneous inhibition of cyclooxygenase 2.
AB  - Pancreatic ductal adenocarcinoma is the fourth leading cause of cancer death
      worldwide, with no satisfactory treatment to date. In this study, we tested
      whether the combined inhibition of cyclooxygenase-2 (COX-2) and class I histone
      deacetylase (HDAC) may results in a better control of pancreatic ductal
      adenocarcinoma. The impact of the concomitant HDAC and COX-2 inhibition on cell
      growth, apoptosis and cell cycle was assessed first in vitro on human pancreas
      BxPC-3, PANC-1 or CFPAC-1 cells treated with chemical inhibitors (SAHA, MS-275
      and celecoxib) or HDAC1/2/3/7 siRNA. To test the potential antitumoral activity
      of this combination in vivo, we have developed and characterized, a refined chick
      chorioallantoic membrane tumor model that histologically and proteomically mimics
      human pancreatic ductal adenocarcinoma. The combination of HDAC1/3 and COX-2
      inhibition significantly impaired proliferation of BxPC-3 cells in vitro and
      stalled entirely the BxPC-3 cells tumor growth onto the chorioallantoic membrane
      in vivo. The combination was more effective than either drug used alone.
      Consistently, we showed that both HDAC1 and HDAC3 inhibition induced the
      expression of COX-2 via the NF-kB pathway. Our data demonstrate, for the first
      time in a Pancreatic Ductal Adenocarcinoma (PDAC) model, a significant action of
      HDAC and COX-2 inhibitors on cancer cell growth, which sets the basis for the
      development of potentially effective new combinatory therapies for pancreatic
      ductal adenocarcinoma patients. 

PMID- 24040392
TI  - Fine tuning of spatial arrangement of enzymes in a PCNA-mediated multienzyme
      complex using a rigid poly-L-proline linker.
AB  - Inspired by natural multienzyme complexes, many types of artificial multienzyme
      complexes have recently been constructed. We previously constructed a self
      assembled complex of a bacterial cytochrome P450 and its ferredoxin and
      ferredoxin reductase partners using heterotrimerization of proliferating cell
      nuclear antigen (PCNA) from Sulfolobus solfataricus. In this study, we inserted
      different peptide linkers between ferredoxin and the PCNA subunit, and examined
      the effect on activity of the self-assembled multienzyme complex. Although the
      activity was affected by the lengths of both the rigid poly-L-proline-rich
      linkers and the flexible Gly4-Ser repeating linkers, the poly-L-proline-rich
      linkers provided the greatest activity enhancement. The optimized poly-L-proline
      rich linker enhanced the activity 1.9-fold compared with the GGGGSLVPRGSGGGGS
      linker used in the previously reported complex, while the Gly4-Ser repeating
      linkers, (G4S)n (n = 1-6), did not yield higher activity than the maximum
      activity by the optimized poly-L-proline linker. Both the rigidity/flexibility
      and length of the peptide linker were found to be important for enhancing the
      overall activity of the multienzyme complex. 

PMID- 24040393
TI  - A Wisp3 Cre-knockin allele produces efficient recombination in spermatocytes
      during early prophase of meiosis I.
AB  - Individuals with the autosomal recessive skeletal disorder Progressive
      Pseudorheumatoid Dysplasia have loss-of-function mutations in WISP3, and aberrant
      WISP3 expression has been detected in tumors from patients with colon and breast
      cancer. In mice however, neither absence nor over-expression of WISP3 was found
      to cause a phenotype, and endogenous Wisp3 expression has been difficult to
      detect. To confirm that Wisp3 knockout mice have no phenotype and to identify
      potential sites of endogenous Wisp3 expression, we generated mice with a knockin
      allele (Wisp3 (GFP-Cre)) designed to express Green Fluorescent Protein (GFP) and
      Cre-recombinase instead of WISP3. Heterozygous and homozygous knockin mice were
      fertile and indistinguishable from their wild-type littermates, confirming that
      mice lacking Wisp3 have no phenotype. We could not detect GFP-expression from the
      knockin allele, but we could detect Cre-expression after crossing mice with the
      knockin allele to Cre-reporter mice; the double heterozygous offspring had
      evidence of Cre-mediated recombination in several tissues. The only tissue that
      had high levels of Cre-mediated recombination was the testis, where recombination
      in spermatocytes occurred by early prophase of meiosis I. As a consequence, males
      that were double heterozygous for a Wisp3 (GFP-Cre) and a floxed allele only
      contributed a recombined allele to their offspring. We detected no evidence of
      Cre-mediated recombination in the female ovary, although when double heterozygous
      females contributed the reporter allele to their offspring it had recombined ~7%
      of the time. Wisp3 (GFP-Cre) expression therefore occurs less frequently and most
      likely at a later stage of oocyte development in female mice compared to male
      mice. We conclude that although WISP3 is dispensable in mice, male mice with a
      Wisp3 (GFP-Cre) allele (Jackson Laboratory stock # 017685) will be useful for
      studying early prophase of meiosis I and for efficiently recombining floxed
      alleles that are passed to offspring. 

PMID- 24040394
TI  - Incidence of community-acquired lower respiratory tract infections and pneumonia
      among older adults in the United Kingdom: a population-based study.
AB  - Community-acquired lower respiratory tract infections (LRTI) and pneumonia (CAP)
      are common causes of morbidity and mortality among those aged >=65 years; a
      growing population in many countries. Detailed incidence estimates for these
      infections among older adults in the United Kingdom (UK) are lacking. We used
      electronic general practice records from the Clinical Practice Research Data
      link, linked to Hospital Episode Statistics inpatient data, to estimate incidence
      of community-acquired LRTI and CAP among UK older adults between April 1997-March
      2011, by age, sex, region and deprivation quintile. Levels of antibiotic
      prescribing were also assessed. LRTI incidence increased with fluctuations over
      time, was higher in men than women aged >=70 and increased with age from 92.21
      episodes/1000 person-years (65-69 years) to 187.91/1000 (85-89 years). CAP
      incidence increased more markedly with age, from 2.81 to 21.81 episodes/1000
      person-years respectively, and was higher among men. For both infection groups,
      increases over time were attenuated after age-standardisation, indicating that
      these rises were largely due to population aging. Rates among those in the most
      deprived quintile were around 70% higher than the least deprived and were
      generally higher in the North of England. GP antibiotic prescribing rates were
      high for LRTI but lower for CAP (mostly due to immediate hospitalisation). This
      is the first study to provide long-term detailed incidence estimates of community
      acquired LRTI and CAP in UK older individuals, taking person-time at risk into
      account. The summary incidence commonly presented for the >=65 age group
      considerably underestimates LRTI/CAP rates, particularly among older individuals
      within this group. Our methodology and findings are likely to be highly relevant
      to health planners and researchers in other countries with aging populations. 

PMID- 24040395
TI  - Synergistic re-activation of epigenetically silenced genes by combinatorial
      inhibition of DNMTs and LSD1 in cancer cells.
AB  - Epigenetic gene silencing, mediated by aberrant promoter DNA hypermethylation and
      repressive histone modifications, is a hallmark of cancer. Although heritable,
      the dynamic nature and potential reversibility through pharmacological
      interventions make such aberrations attractive targets. Since cancers contain
      multiple epigenetic abnormalities, combining therapies that target different
      defects could potentially enhance their individual efficacies. 5-Aza-2'
      deoxycytidine (5-Aza-CdR), FDA-approved drug for the treatment of myelodysplastic
      syndrome, can inhibit DNA methyltransferases (DNMTs) upon incorporation into the
      DNA of dividing cells, resulting in global demethylation. More recently, the
      first histone demethylase, lysine specific demethylase 1 (LSD1), which
      demethylates both histone and non-histone substrates, has become a new target for
      epigenetic therapy. Using, clorgyline, an LSD1 inhibitor (LSD1i) to treat cancer
      cell lines, we show that clorgyline employs two mechanisms of action depending on
      the cell type: it can either induce global DNA demethylation or inhibit LSD1
      driven H3K4me2 and H3K4me1 demethylation to establish an active chromatin
      configuration. We also investigate the therapeutic efficacy of combining 5-Aza
      CdR with clorgyline and determine that this combinatorial treatment has
      synergistic effects on reactivating aberrantly silenced genes by enriching
      H3K4me2 and H3K4me1. Many of the reactivated genes are categorized as cancer
      testis antigens or belong to the interferon-signaling pathway, suggesting
      potential implications for immunotherapy. Together, our results demonstrate that
      combinatorial treatment consisting of a DNMT inhibitor (DNMTi) and an LSD1i have
      enhanced therapeutic values and could improve the efficacy of epigenetic therapy.

PMID- 24040396
TI  - Association between the RAD51 135 G>C polymorphism and risk of cancer: a meta
      analysis of 19,068 cases and 22,630 controls.
AB  - BACKGROUND: RAD51 135G>C can modify promoter activity and the penetrance of
      BRCA1/2 mutations, which plays vital roles in the etiology of various cancer. To
      date, previous published data on the association between RAD51 135G>C
      polymorphism and cancer risk remained controversial. Recent meta-analysis only
      analyzed RAD51 135G>C polymorphism with breast cancer risk, but the results were
      also inconsistent. METHODS: A meta-analysis based on 39 case-control studies was
      performed to investigate the association between cancer susceptibility and RAD51
      135G>C. Odds ratios (OR) with 95% confidence intervals (CIs) were used to assess
      the association in different inheritance models. Heterogeneity among studies was
      tested and sensitivity analysis was applied. RESULTS: Overall, no significant
      association was found between RAD51 135G>C polymorphism and cancer susceptibility
      in any genetic model. In further stratified analysis, significantly elevated
      breast cancer risk was observed in BRCA2 mutation carriers (recessive model: OR =
      4.88, 95% CI = 1.10-21.67; additive model: OR = 4.92, 95% CI = 1.11-21.83).
      CONCLUSIONS: This meta-analysis suggests that RAD51 variant 135C homozygote is
      associated with elevated breast cancer risk among BRCA2 mutation carriers.
      Moreover, our work also points out the importance of new studies for RAD51 135G>C
      association in acute myeloid leukemia, especially in Caucasians, where at least
      some of the covariates responsible for heterogeneity could be controlled, to
      obtain a more conclusive understanding about the function of the RAD51 135G>C
      polymorphism in cancer development.

PMID- 24040397
TI  - Characterization of regulatory dendritic cells that mitigate acute graft-versus
      host disease in older mice following allogeneic bone marrow transplantation.
AB  - Despite improvements in human leukocyte antigen matching and pharmacologic
      prophylaxis, acute graft-versus-host disease (GVHD) is often a fatal complication
      following hematopoietic stem cell transplant (HSCT). Older HSCT recipients
      experience significantly increased morbidity and mortality compared to young
      recipients. Prophylaxis with syngeneic regulatory dendritic cells (DCreg) in
      young bone marrow transplanted (BMT) mice has been shown to decrease GVHD
      associated mortality. To evaluate this approach in older BMT recipients, young (3
      4 months) and older (14-18 months) DCreg were generated using GM-CSF, IL-10, and
      TGFbeta. Analysis of young versus older DCreg following culture revealed no
      differences in phenotype. The efficacy of DCreg treatment in older BMT mice was
      evaluated in a BALB/c->C57Bl/6 model of GVHD; on day 2 post-BMT (d +2), mice
      received syngeneic, age-matched DCreg. Although older DCreg-treated BMT mice
      showed decreased morbidity and mortality compared to untreated BMT mice (all of
      which died), there was a small but significant decrease in the survival of older
      DCreg-treated BMT mice (75% survival) compared to young DCreg-treated BMT mice
      (90% survival). To investigate differences between dendritic cells (DC) in young
      and older DCreg-treated BMT mice that may play a role in DCreg function in vivo,
      DC phenotypes were assessed following DCreg adoptive transfer. Transferred DCreg
      identified in older DCreg-treated BMT mice at d +3 showed significantly lower
      expression of PD-L1 and PIR B compared to DCreg from young DCreg-treated BMT
      mice. In addition, donor DC identified in d +21 DCreg-treated BMT mice displayed
      increased inhibitory molecule and decreased co-stimulatory molecule expression
      compared to d +3, suggesting induction of a regulatory phenotype on the donor DC.
      In conclusion, these data indicate DCreg treatment is effective in the modulation
      of GVHD in older BMT recipients and provide evidence for inhibitory pathways that
      DCreg and donor DC may utilize to induce and maintain tolerance to GVHD. 

PMID- 24040398
TI  - Reducing FLI1 levels in the MRL/lpr lupus mouse model impacts T cell function by
      modulating glycosphingolipid metabolism.
AB  - Systemic Lupus erythematosus (SLE) is an autoimmune disease caused, in part, by
      abnormalities in cells of the immune system including B and T cells. Genetically
      reducing globally the expression of the ETS transcription factor FLI1 by 50% in
      two lupus mouse models significantly improves disease measures and survival
      through an unknown mechanism. In this study we analyze the effects of reducing
      FLI1 in the MRL/lpr lupus prone model on T cell function. We demonstrate that
      adoptive transfer of MRL/lpr Fli1(+/+) or Fli1(+/-) T cells and B cells into Rag1
      deficient mice results in significantly decreased serum immunoglobulin levels in
      animals receiving Fli1(+/-) lupus T cells compared to animals receiving Fli1(+/+)
      lupus T cells regardless of the genotype of co-transferred lupus B cells. Ex vivo
      analyses of MRL/lpr T cells demonstrated that Fli1(+/-) T cells produce
      significantly less IL-4 during early and late disease and exhibited significantly
      decreased TCR-specific activation during early disease compared to Fli1(+/+) T
      cells. Moreover, the Fli1(+/-) T cells expressed significantly less neuraminidase
      1 (Neu1) message and decreased NEU activity during early disease and
      significantly decreased levels of glycosphingolipids during late disease compared
      to Fli1(+/+) T cells. FLI1 dose-dependently activated the Neu1 promoter in mouse
      and human T cell lines. Together, our results suggest reducing FLI1 in lupus
      decreases the pathogenicity of T cells by decreasing TCR-specific activation and
      IL-4 production in part through the modulation of glycosphingolipid metabolism.
      Reducing the expression of FLI1 or targeting the glycosphingolipid metabolic
      pathway in lupus may serve as a therapeutic approach to treating lupus.

PMID- 24040399
TI  - Residential mercury contamination in adobe brick homes in Huancavelica, Peru.
AB  - This is the first study of adobe brick contamination anywhere in the world.
      Huancavelica, Peru is the site of historic cinnabar refining and one of the most
      mercury (Hg) contaminated urban areas in the world. Over 80% of homes in
      Huancavelica are constructed with adobe bricks made from Hg contaminated soil. In
      this study we measured total Hg concentrations in adobe brick, dirt floor,
      surface dust, and air samples from the interior of 60 adobe brick houses located
      in four neighborhoods. Concentrations of total Hg in adobe bricks, dirt floors,
      and surface dust ranged from 8.00 to 1070 ug/g, 3.06 to 926 ug/g, and 0.02 to
      9.69 ug/wipe, respectively, with statistically significant differences between
      the four neighborhoods. Concentrations of Hg in adobe brick and dirt floor
      samples in Huancavelica were orders of magnitude higher than in Ayacucho, a non
      mining town in Peru. A strong correlation exists between total Hg concentrations
      in adobe bricks and dirt floors which confirms that adobe bricks were being made
      on-site and not purchased from an off-site source. A strong correlation between
      surface dust and adobe bricks and dirt floors indicates that walls and floors
      serve as indoor sources of Hg contamination. Elemental Hg vapor concentrations
      were below detection (<0.5 ug/m(3)) in most homes; however in homes with
      detectable levels, concentrations up to 5.1 ug/m(3) were observed. No
      statistically significant differences in Hg vapor measurements were observed
      between neighborhoods. This study demonstrates that building materials used
      widely in developing communities, such as adobe bricks, may be a substantial
      source of residential Hg exposure in silver or gold refining communities where Hg
      is produced or used for amalgamation in artisanal gold production. 

PMID- 24040400
TI  - K(ATP) channel opener diazoxide prevents neurodegeneration: a new mechanism of
      action via antioxidative pathway activation.
AB  - Pharmacological modulation of ATP-sensitive potassium channels has become a
      promising new therapeutic approach for the treatment of neurodegenerative
      diseases due to their role in mitochondrial and cellular protection. For
      instance, diazoxide, a well-known ATP-sensitive potassium channel activator with
      high affinity for mitochondrial component of the channel has been proved to be
      effective in animal models for different diseases such as Alzheimer's disease,
      stroke or multiple sclerosis. Here, we analyzed the ability of diazoxide for
      protecting neurons front different neurotoxic insults in vitro and ex vivo.
      Results showed that diazoxide effectively protects NSC-34 motoneurons from
      glutamatergic, oxidative and inflammatory damage. Moreover, diazoxide decreased
      neuronal death in organotypic hippocampal slice cultures after exicitotoxicity
      and preserved myelin sheath in organotypic cerebellar cultures exposed to pro
      inflammatory demyelinating damage. In addition, we demonstrated that one of the
      mechanisms of actions implied in the neuroprotective role of diazoxide is
      mediated by the activation of Nrf2 expression and nuclear translocation. Nrf2
      expression was increased in NSC-34 neurons in vitro as well as in the spinal cord
      of experimental autoimmune encephalomyelitis animals orally administered with
      diazoxide. Thus, diazoxide is a neuroprotective agent against oxidative stress
      induced damage and cellular dysfunction that can be beneficial for diseases such
      as multiple sclerosis.

PMID- 24040401
TI  - Preosteocytes/osteocytes have the potential to dedifferentiate becoming a source
      of osteoblasts.
AB  - Presently there is no clear evidence for the ability of mature osteogenic lineage
      cells to dedifferentiate. In order to identify and trace mature osteogenic
      lineage cells, we have utilized transgenic mouse models in which the dentin
      matrix protein 1 (Dmp1) promoter drives expression of GFP (active marker) or Cre
      recombinase (historic label) in preosteocytes/osteocytes. In long bone chip
      outgrowth cultures, in which cells on the bone surface were enzymatically
      removed, cells with previous activity of the Dmp1 promoter migrated onto plastic
      and down-regulated Dmp1-GFP expression. Dmp1Cre-labeled cells from these cultures
      had the potential to re-differentiate into the osteogenic lineage, while the
      negative population showed evidence of adipogenesis. We observed numerous Dmp1Cre
      labeled osteoblasts on the surface of bone chips following their in vivo
      transplantation. Our data indicate that cells embedded in bone matrix are motile,
      and once given access to the extra bony milieu will migrate out of their lacunae.
      This population of cells is phenotypically and functionally heterogeneous in
      vitro. Once the preosteocytes/osteocytes leave lacunae, they can dedifferentiate,
      potentially providing an additional source of functional osteoblasts. 

PMID- 24040402
TI  - Norwegian physicians' knowledge of the prices of pharmaceuticals: a survey.
AB  - The objectives of this study are to measure physicians' knowledge of the prices
      of pharmaceuticals, and investigate whether there are differences in knowledge of
      prices between groups of physicians. This article reports on a survey study of
      physicians' knowledge of the prices of pharmaceuticals conducted on a
      representative sample of Norwegian physicians in the autumn of 2010. The
      importance of physicians' knowledge of costs derives from their influence on
      total spending and allocation of limited health-care resources. Physicians are
      important drivers in the effort to contain costs in health care, but only if they
      have the knowledge needed to choose the most cost-effective treatment options. A
      survey was sent to 1543 Norwegian physicians, asking them for price estimates and
      their opinions on the importance of considering the cost of treatment to society
      as a decision factor when treating their patients. This article deals with a
      subsection in which the physicians were asked to estimate the price of five
      pharmaceuticals: simvastatin, alendronate (Fosamax), infliximab (Remicade),
      natalizumab (Tysabri) and escitalopram (Cipralex). The response rate was 65%. For
      all the five pharmaceuticals, more than 50% and as many as 83% gave responses
      that differed more than 50% from the actual drug price. The price of more
      expensive pharmaceuticals was underestimated, while the opposite was the case for
      less expensive medicines. The data show that physicians in general have poor
      knowledge of the prices of the pharmaceuticals they offer their patients.
      However, the physicians who frequently deal with a drug have better knowledge of
      its price than those who do not handle a medication as often. The data also
      suggest that those physicians who agree that cost of care to society is an
      important decision factor have better knowledge of drug prices.

PMID- 24040403
TI  - Reduced processing of facial and postural cues in social anxiety: insights from
      electrophysiology.
AB  - Social anxiety is characterized by fear of evaluative interpersonal situations.
      Many studies have investigated the perception of emotional faces in socially
      anxious individuals and have reported biases in the processing of threatening
      faces. However, faces are not the only stimuli carrying an interpersonal
      evaluative load. The present study investigated the processing of emotional body
      postures in social anxiety. Participants with high and low social anxiety
      completed an attention-shifting paradigm using neutral, angry and happy faces and
      postures as cues. We investigated early visual processes through the P100
      component, attentional fixation on the P2, structural encoding mirrored by the
      N170, and attentional orientation towards stimuli to detect with the P100 locked
      on target occurrence. Results showed a global reduction of P100 and P200
      responses to faces and postures in socially anxious participants as compared to
      non-anxious participants, with a direct correlation between self-reported social
      anxiety levels and P100 and P200 amplitudes. Structural encoding of cues and
      target processing were not modulated by social anxiety, but socially anxious
      participants were slower to detect the targets. These results suggest a reduced
      processing of social postural and facial cues in social anxiety. 

PMID- 24040405
TI  - Coral colonisation of an artificial reef in a turbid nearshore environment,
      Dampier Harbour, western Australia.
AB  - A 0.6 hectare artificial reef of local rock and recycled concrete sleepers was
      constructed in December 2006 at Parker Point in the industrial port of Dampier,
      western Australia, with the aim of providing an environmental offset for a
      nearshore coral community lost to land reclamation. Corals successfully colonised
      the artificial reef, despite the relatively harsh environmental conditions at the
      site (annual water temperature range 18-32 degrees C, intermittent high
      turbidity, frequent cyclones, frequent nearby ship movements). Coral settlement
      to the artificial reef was examined by terracotta tile deployments, and later
      stages of coral community development were examined by in-situ visual surveys
      within fixed 25 x 25 cm quadrats on the rock and concrete substrates. Mean coral
      density on the tiles varied from 113 +/- 17 SE to 909 +/- 85 SE per m(2) over
      five deployments, whereas mean coral density in the quadrats was only 6.0 +/- 1.0
      SE per m(2) at eight months post construction, increasing to 24.0 +/- 2.1 SE per
      m(2) at 62 months post construction. Coral taxa colonising the artificial reef
      were a subset of those on the surrounding natural reef, but occurred in different
      proportions--Pseudosiderastrea tayami, Mycedium elephantotus and Leptastrea
      purpurea being disproportionately abundant on the artificial reef. Coral cover
      increased rapidly in the later stages of the study, reaching 2.3 +/- 0.7 SE % at
      62 months post construction. This study indicates that simple materials of
      opportunity can provide a suitable substrate for coral recruitment in Dampier
      Harbour, and that natural colonisation at the study site remains sufficient to
      initiate a coral community on artificial substrate despite ongoing natural and
      anthropogenic perturbations.

PMID- 24040404
TI  - HIV-1 envelope glycoprotein resistance to monoclonal antibody 2G12 is subject
      specific and context-dependent in macaques and humans.
AB  - HIV-1 Envelope (Env) protein is the sole target of neutralizing antibodies (NAbs)
      that arise during infection to neutralize autologous variants. Under this immune
      pressure, HIV escape variants are continuously selected and over the course of
      infection Env becomes more neutralization resistant. Many common alterations are
      known to affect sensitivity to NAbs, including residues encoding potential N
      linked glycosylation sites (PNGS). Knowledge of Env motifs associated with
      neutralization resistance is valuable for the design of an effective Env-based
      vaccine so we characterized Envs isolated longitudinally from a SHIV(SF162P4)
      infected macaque for sensitivity to neutralizing monoclonal antibodies (MAbs)
      B12, 2G12, 4E10 and 2F5. The early Env, isolated from plasma at day 56 after
      infection, was the most sensitive and the late Env, from day 670, was the most
      resistant to MAbs. We identified four PNGS in these Envs that accumulated over
      time at positions 130, 139, 160 and 397. We determined that removal of these PNGS
      significantly increased neutralization sensitivity to 2G12, and conversely, we
      identified mutations by in silico analyses that contributed resistance to 2G12
      neutralization. In order to expand our understanding of these PNGS, we analyzed
      Envs from clade B HIV-infected human subjects and identified additional glycan
      and amino acid changes that could affect neutralization by 2G12 in a context
      dependent manner. Taken together, these in vitro and in silico analyses of clade
      B Envs revealed that 2G12 resistance is achieved by previously unrecognized PNGS
      substitutions in a context-dependent manner and by subject-specific pathways.

PMID- 24040406
TI  - The Wnt/beta-catenin pathway regulates the expression of the miR-302 cluster in
      mouse ESCs and P19 cells.
AB  - MicroRNAs of the miR-302 cluster are involved in early embryonic development and
      somatic cell reprogramming. Expression of the miR-302 gene is regulated by the
      binding of the pluripotency factors Oct4, Sox2 and Nanog to the miR-302 promoter.
      The specific expression pattern of the miR-302 gene suggested that additional
      transcription factors might be involved in its regulation. Here, we show that the
      miR-302 promoter is a direct target of the Wnt/beta-catenin signaling pathway. We
      found that the miR-302 promoter contains three different functional Tcf/Lef
      binding sites. Two of the three sites were located within the cluster of
      Oct4/Sox2/Nanog binding sites and were essential for Wnt/beta-catenin-mediated
      regulation of the miR-302 gene. Tcf3, the only Tcf/Lef factor that bound to the
      miR-302 promoter, acted as a repressor of miR-302 transcription. Interestingly,
      mutations in the two Tcf/Lef binding sites and the Oct4/Nanog binding sites
      abolished miR-302 promoter responsiveness to Wnt signaling, suggesting that the
      Tcf/Lef and the Oct4/Nanog sites interact genetically. 

PMID- 24040407
TI  - High cost and low survival rate in high comorbidity incident elderly hemodialysis
      patients.
AB  - BACKGROUND: The comorbidity index is a predictor of mortality in dialysis
      patients but there are few reports for predicting elderly dialysis mortality and
      national population-based cost studies on elderly dialysis. The aim of this study
      was to evaluate the long-term mortality of incident elderly dialysis patients
      using the Deyo-Charlson comorbidity index (CCI) and to assess the inpatient and
      outpatient visits along with non-dialysis costs. METHODS: Data were obtained from
      catastrophic illness registration of the Taiwan National Health Insurance
      Research Database. Incident elderly dialysis patients (age >=75 years) receiving
      hemodialysis for more than 90 days between Jan 1, 1998, and Dec 31, 2007, were
      included. Baseline comorbidities were determined one year prior to the first
      dialysis day according to ICD-9 CM codes. Survival time, mortality rate,
      hospitalization time, outpatient visit frequency, and costs were calculated for
      different age and CCI groups. RESULTS: In 10,759 incident elderly hemodialysis
      patients, hazard ratios for all-cause mortality were significantly increased in
      the different age groups (p < 0.001) and CCI patients (p < 0.001). Death rates
      increased with both increasing age and CCI score. High comorbidity incident
      hemodialysis and elderly patients were found to have increased length of hospital
      stay and total hospitalization costs. CONCLUSIONS: This population-based cohort
      study indicated that both age and higher CCI values were predictors of survival
      in incident elderly hemodialysis. Increased costs and mortality rates were
      evident in the oldest patients and in those with high CCI scores. Conservative
      treatment might be considered in high comorbidity and low-survival rate end stage
      renal disease (ESRD) patients.

PMID- 24040408
TI  - Advantage of using allele-specific copy numbers when testing for association in
      regions with common copy number variants.
AB  - Copy number variants (CNV) can be called from SNP-arrays; however, few studies
      have attempted to combine both CNV and SNP calls to test for association with
      complex diseases. Even when SNPs are located within CNVs, two separate
      association analyses are necessary, to compare the distribution of bi-allelic
      genotypes in cases and controls (referred to as SNP-only strategy) and the number
      of copies of a region (referred to as CNV-only strategy). However, when disease
      susceptibility is actually associated with allele specific copy-number states,
      the two strategies may not yield comparable results, raising a series of
      questions about the optimal analytical approach. We performed simulations of the
      performance of association testing under different scenarios that varied genotype
      frequencies and inheritance models. We show that the SNP-only strategy lacks
      power under most scenarios when the SNP is located within a CNV; frequently it is
      excluded from analysis as it does not pass quality control metrics either because
      of an increased rate of missing calls or a departure from fitness for Hardy
      Weinberg proportion. The CNV-only strategy also lacks power because the
      association testing depends on the allele which copy number varies. The combined
      strategy performs well in most of the scenarios. Hence, we advocate the use of
      this combined strategy when testing for association with SNPs located within
      CNVs. 

PMID- 24040409
TI  - Amniotic fluid stem cells from EGFP transgenic mice attenuate hyperoxia-induced
      acute lung injury.
AB  - High concentrations of oxygen aggravate the severity of lung injury in patients
      requiring mechanical ventilation. Although mesenchymal stem cells have been shown
      to effectively attenuate various injured tissues, there is limited information
      regarding a role for amniotic fluid stem cells (AFSCs) in treating acute lung
      injury. We hypothesized that intravenous delivery of AFSCs would attenuate lung
      injury in an experimental model of hyperoxia-induced lung injury. AFSCs were
      isolated from EGFP transgenic mice. The in vitro differentiation, surface
      markers, and migration of the AFSCs were assessed by specific staining, flow
      cytometry, and a co-culture system, respectively. The in vivo therapeutic
      potential of AFSCs was evaluated in a model of acute hyperoxia-induced lung
      injury in mice. The administration of AFSCs significantly reduced the hyperoxia
      induced pulmonary inflammation, as reflected by significant reductions in lung
      wet/dry ratio, neutrophil counts, and the level of apoptosis, as well as reducing
      the levels of inflammatory cytokine (IL-1beta, IL-6, and TNF-alpha) and early
      stage fibrosis in lung tissues. Moreover, EGFP-expressing AFSCs were detected and
      engrafted into a peripheral lung epithelial cell lineage by fluorescence
      microscopy and DAPI stain. Intravenous administration of AFSCs may offer a new
      therapeutic strategy for acute lung injury (ALI), for which efficient treatments
      are currently unavailable. 

PMID- 24040410
TI  - Expression of angiopoietin-2 and vascular endothelial growth factor receptor-3
      correlates with lymphangiogenesis and angiogenesis and affects survival of oral
      squamous cell carcinoma.
AB  - BACKGROUND: Both Ang-2 and VEGFR-3 are major regulators of angiogenesis and
      lymphangiogenesis, respectively, and thus may affect prognosis of OSCC. We sought
      to determine the associations between Ang-2 and VEGFR-3 expression and survival
      of OSCC. METHODS: Ang-2 and VEGFR-3 expression was determined
      immunohistochemically in tumor tissues from 112 patients with OSCC; OSCC-adjacent
      noncancerous oral tissue from 85 OSCC patients; and normal oral mucosa from 37
      cancer-free individuals. A log-rank test and Cox proportional hazard models were
      used to compare survival among different groups with expression of Ang-2 and
      VEGFR-3. RESULTS: Ang-2 and VEGFR-3 expression was upregulated in OSCC compared
      to nontumor tissue (all P<0.05). High Ang-2 expression positively correlated with
      microvessel density (MVD) (P<0.01), and high VEGFR-3 expression positively
      correlated with lymph node metastasis (P<0.01) and lymphatic vessel density (LVD)
      (P<0.01). The patients with high expression of Ang-2 alone or in combination with
      VEGFR-3 had a significantly worse survival than in patients with low expression
      of Ang-2 or any other co-expression status (all P<0.05), respectively.
      Furthermore, multivariable analysis showed that patients with high expression of
      Ang-2 alone or in combination with VEGFR-3 had a significantly increased risk of
      death compared with those with low expression of Ang-2 or any other co-expression
      status (HR, 2.7, 95% CI, 1.1-6.2 and 5.0, 1.3-15.4, respectively). CONCLUSIONS:
      These results suggest that increased expression in tumors of Ang-2 may
      individually, or in combination with VEGFR-3, predict poor prognosis of OSCC.

PMID- 24040411
TI  - Identification of an evolutionarily conserved cis-regulatory element controlling
      the Peg3 imprinted domain.
AB  - The mammalian Peg3 domain harbors more than 20 evolutionarily conserved regions
      (ECRs) that are spread over the 250-kb genomic interval. The majority of these
      ECRs are marked with two histone modifications, H3K4me1 and H3K27ac, suggesting
      potential roles as distant regulatory elements for the transcription of the
      nearby imprinted genes. In the current study, the chromatin conformation capture
      (3C) method was utilized to detect potential interactions of these ECRs with the
      imprinted genes. According to the results, one region, ECR18, located 200-kb
      upstream of Peg3 interacts with the two promoter regions of Peg3 and Zim2. The
      observed interaction is most prominent in brain, but was also detected in testis.
      Histone modification and DNA methylation on ECR18 show no allele bias, implying
      that this region is likely functional on both alleles. In vitro assays also
      reveal ECR18 as a potential enhancer or repressor for the promoter of Peg3.
      Overall, these results indicate that the promoters of several imprinted genes in
      the Peg3 domain interact with one evolutionarily conserved region, ECR18, and
      further suggest that ECR18 may play key roles in the transcription and imprinting
      control of the Peg3 domain as a distant regulatory element. 

PMID- 24040412
TI  - Genetic analysis of growth traits in Polled Nellore cattle raised on pasture in
      tropical region using Bayesian approaches.
AB  - Components of (co)variance and genetic parameters were estimated for adjusted
      weights at ages 120 (W120), 240 (W240), 365 (W365) and 450 (W450) days of Polled
      Nellore cattle raised on pasture and born between 1987 and 2010. Analyses were
      performed using an animal model, considering fixed effects: herd-year-season of
      birth and calf sex as contemporary groups and the age of cow as a covariate.
      Gibbs Samplers were used to estimate (co)variance components, genetic parameters
      and additive genetic effects, which accounted for great proportion of total
      variation in these traits. High direct heritability estimates for the growth
      traits were revealed and presented mean 0.43, 0.61, 0.72 and 0.67 for W120, W240,
      W365 and W450, respectively. Maternal heritabilities were 0.07 and 0.08 for W120
      and W240, respectively. Direct additive genetic correlations between the weight
      at 120, 240, 365 and 450 days old were strong and positive. These estimates
      ranged from 0.68 to 0.98. Direct-maternal genetic correlations were negative for
      W120 and W240. The estimates ranged from -0.31 to -0.54. Estimates of maternal
      heritability ranged from 0.056 to 0.092 for W120 and from 0.064 to 0.096 for
      W240. This study showed that genetic progress is possible for the growth traits
      we studied, which is a novel and favorable indicator for an upcoming and
      promising Polled Zebu breed in Tropical regions. Maternal effects influenced the
      performance of weight at 120 and 240 days old. These effects should be taken into
      account in genetic analyses of growth traits by fitting them as a genetic or a
      permanent environmental effect, or even both. In general, due to a medium-high
      estimate of environmental (co)variance components, management and feeding
      conditions for Polled Nellore raised at pasture in tropical regions of Brazil
      needs improvement and growth performance can be enhanced. 

PMID- 24040413
TI  - Chronic pravastatin but not atorvastatin treatment impairs cognitive function in
      two rodent models of learning and memory.
AB  - Statins are some of the most commonly prescribed drugs and are used to reduce
      blood cholesterol. Recent evidence suggests that, in some patients, they may
      adversely influence cognitive function including causing memory impairments.
      These clinical observations have led to statin prescriptions now including a
      warning about possible cognitive impairments. In order to better understand the
      relationship between statin treatment and cognitive function, studies in animals
      are needed. The present study investigated the effects of chronic treatment with
      two statins, pravastatin and atorvastatin, in two rodent models of learning and
      memory. Adult rats were treated once daily with pravastatin (10 mg/kg, orally) or
      atorvostatin (10 mg/kg, orally) for 18 days. Before, during and after treatment,
      animals were tested in a simple discrimination and reversal learning task. On the
      last day of treatment and following one week withdrawal, animals were also tested
      in a task of novel object discrimination. Pravastatin tended to impair learning
      over the last few days of treatment and this effect was fully reversed once
      treatment ceased. In the novel object discrimination task, pravastatin
      significantly impaired object recognition memory. No effects were observed for
      atorvostatin in either task. These data suggest that chronic treatment with
      pravastatin impairs working and recognition memory in rodents. The reversibility
      of the effects on cessation of treatment is similar to what has been observed in
      patients, but the lack of effect of atorvostatin suggests that lipophilicity may
      not be a major factor influencing statin-induced cognitive impairments.

PMID- 24040414
TI  - The application of closed reduction internal fixation and iliac bone block
      grafting in the treatment of acute displaced femoral neck fractures.
AB  - OBJECTIVE: This study aimed to evaluate the preliminary clinical and radiographic
      outcomes of acute displaced femoral neck fracture treated by closed reduction and
      internal fixation (CRIF) with free iliac bone block grafting with comparison to a
      routine protocol of CRIF without bone grafting. METHODS: From December 2008 to
      February 2010, 220 adult patients with acute displaced femoral neck fractures
      were enrolled in this study. In study group, there were 124 patients (57 males,
      67 females) with a mean age of 44.8 years (range, 20-64 years). There were 70
      transcervical fractures and 54 subcapital fractures. The patients were treated by
      CRIF and free iliac bone block grafting. The control group consisted of 96 adult
      patients (46 males, 50 females) with a mean age of 46.3 years (range, 23-64
      years). There were 61 transcervical fractures and 35 subcapital fractures. The
      patients in control group were treated by CRIF without bone grafting. RESULTS: In
      study group, 112 patients were followed up for an average of 27.4 months (range,
      24-34 months). All fractures healed within 5 months. However, 10 patients
      presented AVN of the femoral heads. The mean Harris score was 88.6 (range, 41
      100). In control group, 68 patients were followed up for an average of 31.2
      months (range, 24-42 months). The rates of AVN of the femoral head and fracture
      nonunion in control group were 26.5% (18/68) and 16.2% (11/68), respectively,
      significantly higher than those in study group (both P<0.05). The mean Harris
      score in control group was 83.8 (41-100), significantly lower than that in study
      group (P<0.05). CONCLUSION: Acute displaced femoral neck fractures can be treated
      by CRIF and free iliac bone block grafting in a minimally invasive manner. This
      technique can guarantee uneventful fracture healing and significantly reduce the
      rate of femoral head osteonecrosis.

PMID- 24040415
TI  - Unique organizational and functional features of the cytochrome c maturation
      system in Shewanella oneidensis.
AB  - Shewanella are renowned for their ability to respire on a wide range of electron
      acceptors, which has been partially accredited to the presence of a large number
      of the c-type cytochromes. In the model species S. oneidensis MR-1, at least 41
      genes encode c-type cytochromes that are predicted to be intact, thereby likely
      functional. Previously, in-frame deletion mutants for 36 of these genes were
      obtained and characterized. In this study, first we completed the construction of
      an entire set of c-type cytochrome mutants utilizing a newly developed att-based
      mutagenesis approach, which is more effective and efficient than the approach
      used previously by circumventing the conventional cloning. Second, we
      investigated the cytochrome c maturation (Ccm) system in S. oneidensis. There are
      two loci predicted to encode components of the Ccm system, SO0259-SO0269 and
      SO0476-SO0478. The former is proven essential for cytochrome c maturation whereas
      the latter is dispensable. Unlike the single operon organization observed in
      other gamma-proteobacteria, genes at the SO0259-SO0269 locus are uniquely
      organized into four operons, ccmABCDE, scyA, SO0265, and ccmFGH-SO0269.
      Functional analysis revealed that the SO0265 gene rather than the scyA and SO0269
      genes are relevant to cytochrome c maturation. 

PMID- 24040416
TI  - Protective effects of resveratrol in experimental retinal detachment.
AB  - BACKGROUND: Oxidative stress is one of the major factors that trigger
      photoreceptor apoptosis. To investigate whether resveratrol, a potent antioxidant
      and small molecule activator of the FoxO pathway, would be neuroprotective
      against photoreceptor cell death in a rodent model of retinal detachment.
      METHODS: Retinal detachment was created in adult Brown Norway rats by subretinal
      injection of sodium hyaluronate. The animals were treated daily with vehicle or
      resveratrol (20 mg/kg) intraperitoneal injection. Photoreceptor death was
      assessed by counting the number of apoptotic cells with TdT-dUTP terminal nick
      end labeling (TUNEL) and measurement of the outer nuclear layer (ONL) thickness 3
      days after RD. Changes in expression of FoxO1a, FoxO3a, and FoxO4 were analyzed
      by western blot. The activity of caspase 3, caspase 8, caspase 9, spectrin and
      their cleavage forms were studied. RESULTS: Three days after retinal detachment,
      caspase 3, caspase 8 and caspase 9 were significantly activated in the detached
      retina. Spectrin cleavage products at 120 and 145 kDa were also detected. Both
      caspase and calpain activation are involved in apoptotic photoreceptor cell death
      in detached retinas. Treatment with resveratrol increases FoxO1a, FoxO3a, and
      FoxO4 protein expression in detached retinas only. Resveratrol treatment
      decreases activation of intrinsic and extrinsic caspase apoptotic pathways
      triggered by RD. The number of TUNEL-positive cells decreases from 1301+/-51
      cells/mm(2) in control groups to 430+/-35 cells/mm(2) in treatment groups
      (p<0.05). Resveratrol treatment also demonstrates 59% less ONL thickness loss
      compared to controls. CONCLUSIONS: Resveratrol treatment up-regulates the FoxO
      family and blocks Caspase3, 8, and 9 activation. Resveratrol has the potential to
      be used as a novel therapeutic agent for preventing vision loss in diseases
      characterized by photoreceptor detachment.

PMID- 24040417
TI  - DNA topoisomerases participate in fragility of the oncogene RET.
AB  - Fragile site breakage was previously shown to result in rearrangement of the RET
      oncogene, resembling the rearrangements found in thyroid cancer. Common fragile
      sites are specific regions of the genome with a high susceptibility to DNA
      breakage under conditions that partially inhibit DNA replication, and often
      coincide with genes deleted, amplified, or rearranged in cancer. While a
      substantial amount of work has been performed investigating DNA repair and cell
      cycle checkpoint proteins vital for maintaining stability at fragile sites,
      little is known about the initial events leading to DNA breakage at these sites.
      The purpose of this study was to investigate these initial events through the
      detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in
      which 144 APH-induced DNA breakpoints were mapped on the nucleotide level in
      human thyroid cells within intron 11 of RET, the breakpoint cluster region found
      in patients. These breakpoints were located at or near DNA topoisomerase I and/or
      II predicted cleavage sites, as well as at DNA secondary structural features
      recognized and preferentially cleaved by DNA topoisomerases I and II. Co
      treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors,
      betulinic acid and merbarone, significantly decreased APH-induced fragile site
      breakage within RET intron 11 and within the common fragile site FRA3B. These
      data demonstrate that DNA topoisomerases I and II are involved in initiating APH
      induced common fragile site breakage at RET, and may engage the recognition of
      DNA secondary structures formed during perturbed DNA replication. 

PMID- 24040419
TI  - Central auditory masking by an illusory tone.
AB  - Many natural sounds fluctuate over time. The detectability of sounds in a
      sequence can be reduced by prior stimulation in a process known as forward
      masking. Forward masking is thought to reflect neural adaptation or neural
      persistence in the auditory nervous system, but it has been unclear where in the
      auditory pathway this processing occurs. To address this issue, the present study
      used a "Huggins pitch" stimulus, the perceptual effects of which depend on
      central auditory processing. Huggins pitch is an illusory tonal sensation
      produced when the same noise is presented to the two ears except for a narrow
      frequency band that is different (decorrelated) between the ears. The pitch
      sensation depends on the combination of the inputs to the two ears, a process
      that first occurs at the level of the superior olivary complex in the brainstem.
      Here it is shown that a Huggins pitch stimulus produces more forward masking in
      the frequency region of the decorrelation than a noise stimulus identical to the
      Huggins-pitch stimulus except with perfect correlation between the ears. This
      stimulus has a peripheral neural representation that is identical to that of the
      Huggins-pitch stimulus. The results show that processing in, or central to, the
      superior olivary complex can contribute to forward masking in human listeners. 

PMID- 24040418
TI  - Protein phosphatase 1 beta paralogs encode the zebrafish myosin phosphatase
      catalytic subunit.
AB  - BACKGROUND: The myosin phosphatase is a highly conserved regulator of actomyosin
      contractility. Zebrafish has emerged as an ideal model system to study the in
      vivo role of myosin phosphatase in controlling cell contractility, cell movement
      and epithelial biology. Most work in zebrafish has focused on the regulatory
      subunit of the myosin phosphatase called Mypt1. In this work, we examined the
      critical role of Protein Phosphatase 1, PP1, the catalytic subunit of the myosin
      phosphatase. METHODOLOGY/PRINCIPAL FINDINGS: We observed that in zebrafish two
      paralogous genes encoding PP1beta, called ppp1cba and ppp1cbb, are both broadly
      expressed during early development. Furthermore, we found that both gene products
      interact with Mypt1 and assemble an active myosin phosphatase complex. In
      addition, expression of this complex results in dephosphorylation of the myosin
      regulatory light chain and large scale rearrangements of the actin cytoskeleton.
      Morpholino knock-down of ppp1cba and ppp1cbb results in severe defects in
      morphogenetic cell movements during gastrulation through loss of myosin
      phosphatase function. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates that
      zebrafish have two genes encoding PP1beta, both of which can interact with Mypt1
      and assemble an active myosin phosphatase. In addition, both genes are required
      for convergence and extension during gastrulation and correct dosage of the
      protein products is required.

PMID- 24040421
TI  - Negative life events in childhood as risk indicators of labour market
      participation in young adulthood: a prospective birth cohort study.
AB  - BACKGROUND: Most previous studies on reliance on social benefits have focused on
      health, sickness absence, work environment and socioeconomic status in adulthood.
      Extending the focus to include early life circumstances may improve our
      understanding of processes leading to educational and occupational
      marginalisation and exclusion. The aim of this study was to investigate if
      multiple negative life events in childhood determined future labour market
      participation, and to identify important negative life events for labour market
      participation in young adulthood. METHODS: Of a cohort of 3,681 born in 1989 in
      the county of Ringkjoebing, Denmark, 3,058 (83%) completed a questionnaire in
      2004. They were followed in a register on social benefits for 12 months in 2010
      2011. Logistic regression analyses were used to investigate associations between
      negative life events in childhood and future labour market participation, taking
      into account effects of socio-economic position, school performance, educational
      plans, vocational expectations and general health. RESULTS: A total of 17.1%
      (19.9% males, 14.4% females) received social benefits for at least 4 weeks during
      follow-up. Labour market participation decreased with number of negative life
      events, especially for females: Females who had experienced their parents'
      divorce, had been abused, or had witnessed a violent event, showed decreased
      labour market participation, when adjusting for SES, school performance,
      educational plans, vocational expectations and general health at baseline.
      Attributable fractions ranged from 2.4% (parents' alcohol/drug abuse) to 16.1%
      (parents' divorce) for women. For men, risk estimates were lower and
      insignificant in the most adjusted models. Attributable fractions ranged from
      1.0% (parents' alcohol/drug abuse) to 4.9% for witnessing a violent event.
      CONCLUSIONS: Information on childhood conditions may increase the understanding
      of determinants of labour market participation for young adults. Knowledge of
      negative life events in childhood should be taken into account when considering
      determinants of labour market participation and identifying high-risk groups.

PMID- 24040422
TI  - Effects of laboratory housing on exploratory behaviour, novelty discrimination
      and spatial reference memory in a subterranean, solitary rodent, the Cape mole
      rat (Georychus capensis).
AB  - A large number of laboratory and field based studies are being carried out on
      mole-rats, both in our research group and others. Several studies have
      highlighted the development of adverse behaviours in laboratory animals and have
      emphasised the importance of enrichment for captive animals. Hence we were
      interested in evaluating how laboratory housing would affect behavioural
      performance in mole-rats. We investigated exploratory behaviour, the ability to
      discriminate between novel and familiar environments and reference memory in the
      solitary Cape mole-rat (Georychus capensis). Our data showed that both wild and
      captive animals readily explore open spaces and tunnels. Wild animals were
      however more active than their captive counterparts. In the Y maze two trial
      discrimination task, wild animals failed to discriminate between novel and
      familiar environments, while laboratory housed mole-rats showed preferential
      spatial discrimination in terms of the length of time spent in the novel arm. The
      performance of the laboratory and wild animals were similar when tested for
      reference memory in the Y maze, both groups showed a significant improvement
      compared to the first day, from the 3rd day onwards. Wild animals made more
      mistakes whereas laboratory animals were slower in completing the task. The
      difference in performance between wild and laboratory animals in the Y-maze may
      be as a result of the lower activity of the laboratory animals. Laboratory
      maintained Cape mole-rats show classic behaviours resulting from a lack of
      stimulation such as reduced activity and increased aggression. However, they do
      display an improved novelty discrimination compared to the wild animals. Slower
      locomotion rate of the laboratory animals may increase the integration time of
      stimuli, hence result in a more thorough inspection of the surroundings. Unlike
      the captive animals, wild animals show flexibility in their responses to
      unpredictable events, which is an important requirement under natural living
      conditions.

PMID- 24040420
TI  - Extracellular matrix collagen alters cell proliferation and cell cycle
      progression of human uterine leiomyoma smooth muscle cells.
AB  - Uterine leiomyomas (ULs) are benign tumors occurring in the majority of
      reproductive aged women. Despite the high prevalence of these tumors, little is
      known about their etiology. A hallmark of ULs is the excessive deposition of
      extracellular matrix (ECM), primarily collagens. Collagens are known to modulate
      cell behavior and function singularly or through interactions with integrins and
      growth factor-mediated mitogenic pathways. To better understand the pathogenesis
      of ULs and the role of ECM collagens in their growth, we investigated the
      interaction of leiomyoma smooth muscle cells (LSMCs) with two different forms of
      collagen, non-polymerized collagen (monomeric) and polymerized collagen
      (fibrillar), in the absence or presence of platelet-derived growth factor (PDGF),
      an abundant growth factor in ULs. Primary cultures of human LSMCS from
      symptomatic patients were grown on these two different collagen matrices and
      their morphology, cytoskeletal organization, cellular proliferation, and
      signaling pathways were evaluated. Our results showed that LSMCs had distinct
      morphologies on the different collagen matrices and their basal as well as PDGF
      stimulated proliferation varied on these matrices. These differences in
      proliferation were accompanied by changes in cell cycle progression and p21, an
      inhibitory cell cycle protein. In addition we found alterations in the
      phosphorylation of focal adhesion kinase, cytoskeletal reorganization, and
      activation of the mitogen activated protein kinase (MAPK) signaling pathway. In
      conclusion, our results demonstrate a direct effect of ECM on the proliferation
      of LSMCs through interplay between the collagen matrix and the PDGF-stimulated
      MAPK pathway. In addition, these findings will pave the way for identifying novel
      therapeutic approaches for ULs that target ECM proteins and their signaling
      pathways in ULs. 

PMID- 24040423
TI  - A small conductance calcium-activated K+ channel in C. elegans, KCNL-2, plays a
      role in the regulation of the rate of egg-laying.
AB  - In the nervous system of mice, small conductance calcium-activated potassium (SK)
      channels function to regulate neuronal excitability through the generation of a
      component of the medium afterhyperpolarization that follows action potentials. In
      humans, irregular action potential firing frequency underlies diseases such as
      ataxia, epilepsy, schizophrenia and Parkinson's disease. Due to the complexity of
      studying protein function in the mammalian nervous system, we sought to
      characterize an SK channel homologue, KCNL-2, in C. elegans, a genetically
      tractable system in which the lineage of individual neurons was mapped from their
      early developmental stages. Sequence analysis of the KCNL-2 protein reveals that
      the six transmembrane domains, the potassium-selective pore and the calmodulin
      binding domain are highly conserved with the mammalian homologues. We used
      widefield and confocal fluorescent imaging to show that a fusion construct of
      KCNL-2 with GFP in transgenic lines is expressed in the nervous system of C.
      elegans. We also show that a KCNL-2 null strain, kcnl-2(tm1885), demonstrates a
      mild egg-laying defective phenotype, a phenotype that is rescued in a KCNL-2
      dependent manner. Conversely, we show that transgenic lines that overexpress KCNL
      2 demonstrate a hyperactive egg-laying phenotype. In this study, we show that the
      vulva of transgenic hermaphrodites is highly innervated by neuronal processes and
      by the VC4 and VC5 neurons that express GFP-tagged KCNL-2. We propose that KCNL-2
      functions in the nervous system of C. elegans to regulate the rate of egg-laying.

PMID- 24040424
TI  - Theoretical Investigation of Optical Detection and Recognition of Single
      Biological Molecules Using Coherent Dynamics of Exciton-Plasmon Coupling.
AB  - We use quantum coherence in a system consisting of one metallic nanorod and one
      semi-conductor quantum dot to investigate a plasmonic nanosensor capable of
      digital optical detection and recognition of single biological molecules. In such
      a sensor the adsorption of a specific molecule to the nanorod turns off the
      emission of the system when it interacts with an optical pulse having a certain
      intensity and temporal width. The proposed quantum sensors can count the number
      of molecules of the same type or differentiate between molecule types with
      digital optical signals that can be measured with high certainty. We show that
      these sensors are based on the ultrafast upheaval of coherent dynamics of the
      system and the removal of coherent blockage of energy transfer from the quantum
      dot to the nanorod once the adsorption process has occurred.

PMID- 24040425
TI  - Defining the Safety of Anacetrapib, a CETP Inhibitor, in Patients at High Risk
      for Coronary Heart Disease: the DEFINE study.

PMID- 24040426
TI  - Evidence of local persistence of human anthrax in the country of georgia
      associated with environmental and anthropogenic factors.
AB  - BACKGROUND: Anthrax is a soil-borne disease caused by the bacterium Bacillus
      anthracis and is considered a neglected zoonosis. In the country of Georgia,
      recent reports have indicated an increase in the incidence of human anthrax.
      Identifying sub-national areas of increased risk may help direct appropriate
      public health control measures. The purpose of this study was to evaluate the
      spatial distribution of human anthrax and identify environmental/anthropogenic
      factors associated with persistent clusters. METHODS/FINDINGS: A database of
      human cutaneous anthrax in Georgia during the period 2000-2009 was constructed
      using a geographic information system (GIS) with case data recorded to the
      community location. The spatial scan statistic was used to identify persistence
      of human cutaneous anthrax. Risk factors related to clusters of persistence were
      modeled using a multivariate logistic regression. Areas of persistence were
      identified in the southeastern part of the country. Results indicated that the
      persistence of human cutaneous anthrax showed a strong positive association with
      soil pH and urban areas. CONCLUSIONS/SIGNIFICANCE: Anthrax represents a
      persistent threat to public and veterinary health in Georgia. The findings here
      showed that the local level heterogeneity in the persistence of human cutaneous
      anthrax necessitates directed interventions to mitigate the disease. High risk
      areas identified in this study can be targeted for public health control measures
      such as farmer education and livestock vaccination campaigns.

PMID- 24040427
TI  - Infection of domestic dogs in peru by zoonotic bartonella species: a cross
      sectional prevalence study of 219 asymptomatic dogs.
AB  - Bartonella species are emerging infectious organisms transmitted by arthropods
      capable of causing long-lasting infection in mammalian hosts. Among over 30
      species described from four continents to date, 15 are known to infect humans,
      with eight of these capable of infecting dogs as well. B. bacilliformis is the
      only species described infecting humans in Peru; however, several other
      Bartonella species were detected in small mammals, bats, ticks, and fleas in that
      country. The objective of this study was to determine the serological and/or
      molecular prevalence of Bartonella species in asymptomatic dogs in Peru in order
      to indirectly evaluate the potential for human exposure to zoonotic Bartonella
      species. A convenient sample of 219 healthy dogs was obtained from five cities
      and three villages in Peru. EDTA-blood samples were collected from 205 dogs,
      whereas serum samples were available from 108 dogs. The EDTA-blood samples were
      screened by PCR followed by nucleotide sequencing for species identification.
      Antibodies against B. vinsonii berkhoffii and B. rochalimae were detected by IFA
      (cut-off of 1?64). Bartonella DNA was detected in 21 of the 205 dogs (10%).
      Fifteen dogs were infected with B. rochalimae, while six dogs were infected with
      B. v. berkhoffii genotype III. Seropositivity for B. rochalimae was detected in
      67 dogs (62%), and for B. v. berkhoffii in 43 (40%) of the 108 dogs. Reciprocal
      titers >=1?256 for B. rochalimae were detected in 19% of dogs, and for B. v.
      berkhoffii in 6.5% of dogs. This study identifies for the first time a population
      of dogs exposed to or infected with zoonotic Bartonella species, suggesting that
      domestic dogs may be the natural reservoir of these zoonotic organisms. Since
      dogs are epidemiological sentinels, Peruvian humans may be exposed to infections
      with B. rochalimae or B. v. berkhoffii. 

PMID- 24040428
TI  - A high force of plasmodium vivax blood-stage infection drives the rapid
      acquisition of immunity in papua new guinean children.
AB  - BACKGROUND: When both parasite species are co-endemic, Plasmodium vivax incidence
      peaks in younger children compared to P. falciparum. To identify differences in
      the number of blood stage infections of these species and its potential link to
      acquisition of immunity, we have estimated the molecular force of blood-stage
      infection of P. vivax ((mol)FOB, i.e. the number of genetically distinct blood
      stage infections over time), and compared it to previously reported values for P.
      falciparum. METHODS: P. vivax (mol)FOB was estimated by high resolution
      genotyping parasites in samples collected over 16 months in a cohort of 264 Papua
      New Guinean children living in an area highly endemic for P. falciparum and P.
      vivax. In this cohort, P. vivax episodes decreased three-fold over the age range
      of 1-4.5 years. RESULTS: On average, children acquired 14.0 new P. vivax blood
      stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness
      was strongly associated with mol FOB (incidence rate ratio (IRR) = 1.99, 95%
      confidence interval (CI95) [1.80, 2.19]), (mol)FOB did not change with age. The
      incidence of P. vivax showed a faster decrease with age in children with high
      (IRR = 0.49, CI95 [0.38, 0.64] p<0.001) compared to those with low exposure (IRR
      = 0.63, CI95[0.43, 0.93] p = 0.02). CONCLUSION: P. vivax (mol)FOB is considerably
      higher than P. falciparum (mol)FOB (5.5 clones/child/year-at-risk). The high
      number of P. vivax clones that infect children in early childhood contribute to
      the rapid acquisition of immunity against clinical P. vivax malaria.

PMID- 24040429
TI  - Administration of E2 and NS1 siRNAs inhibit chikungunya virus replication in
      vitro and protects mice infected with the virus.
AB  - BACKGROUND: Chikungunya virus (CHIKV) has reemerged as a life threatening
      pathogen and caused large epidemics in several countries. So far, no licensed
      vaccine or effective antivirals are available and the treatment remains
      symptomatic. In this context, development of effective and safe prophylactics and
      therapeutics assumes priority. METHODS: We evaluated the efficacy of the siRNAs
      against ns1 and E2 genes of CHIKV both in vitro and in vivo. Four siRNAs each,
      targeting the E2 (Chik-1 to Chik-4) and ns1 (Chik-5 to Chik-8) genes were
      designed and evaluated for efficiency in inhibiting CHIKV growth in vitro and in
      vivo. Chik-1 and Chik-5 siRNAs were effective in controlling CHIKV replication in
      vitro as assessed by real time PCR, IFA and plaque assay. CONCLUSIONS: CHIKV
      replication was completely inhibited in the virus-infected mice when administered
      72 hours post infection. The combination of Chik-1 and Chik-5 siRNAs exhibited
      additive effect leading to early and complete inhibition of virus replication.
      These findings suggest that RNAi capable of inhibiting CHIKV growth might
      constitute a new therapeutic strategy for controlling CHIKV infection and
      transmission.

PMID- 24040430
TI  - Hookworm infection and environmental factors in mbeya region, Tanzania: a cross
      sectional, population-based study.
AB  - BACKGROUND: Hookworm disease is one of the most common infections and cause of a
      high disease burden in the tropics and subtropics. Remotely sensed ecological
      data and model-based geostatistics have been used recently to identify areas in
      need for hookworm control. METHODOLOGY: Cross-sectional interview data and stool
      samples from 6,375 participants from nine different sites in Mbeya region, south
      western Tanzania, were collected as part of a cohort study. Hookworm infection
      was assessed by microscopy of duplicate Kato-Katz thick smears from one stool
      sample from each participant. A geographic information system was used to obtain
      remotely sensed environmental data such as land surface temperature (LST),
      vegetation cover, rainfall, and elevation, and combine them with hookworm
      infection data and with socio-demographic and behavioral data. Uni- and
      multivariable logistic regression was performed on sites separately and on the
      pooled dataset. PRINCIPAL FINDINGS: Univariable analyses yielded significant
      associations for all ecological variables. Five ecological variables stayed
      significant in the final multivariable model: population density (odds ratio (OR)
      = 0.68; 95% confidence interval (CI) = 0.63-0.73), mean annual vegetation density
      (OR = 0.11; 95% CI = 0.06-0.18), mean annual LST during the day (OR = 0.81; 95%
      CI = 0.75-0.88), mean annual LST during the night (OR = 1.54; 95% CI = 1.44
      1.64), and latrine coverage in household surroundings (OR = 1.02; 95% CI = 1.01
      1.04). Interaction terms revealed substantial differences in associations of
      hookworm infection with population density, mean annual enhanced vegetation
      index, and latrine coverage between the two sites with the highest prevalence of
      infection. CONCLUSION/SIGNIFICANCE: This study supports previous findings that
      remotely sensed data such as vegetation indices, LST, and elevation are strongly
      associated with hookworm prevalence. However, the results indicate that the
      influence of environmental conditions can differ substantially within a
      relatively small geographic area. The use of large-scale associations as a
      predictive tool on smaller scales is therefore problematic and should be handled
      with care.

PMID- 24040431
TI  - Suppression of virus specific immune responses by IL-10 in acute dengue
      infection.
AB  - BACKGROUND: Elevated IL-10 has been shown to be associated with severe dengue
      infection (DI). We proceeded to investigate the role of IL-10 in the pathogenesis
      of acute DI. MATERIALS AND METHODS: Ex vivo and cultured IFNgamma ELISpot assays
      for dengue virus (DENV) NS3 protein and non dengue viral proteins were carried
      out in 26 patients with acute DI (16 with dengue haemorrhagic fever) and 12
      healthy dengue seropositive individuals from Sri Lanka. DENV serotype specific
      (SS) responses were determined by using a panel of SS peptides. RESULTS: Serum IL
      10 level were significantly higher (p = 0.02) in those who did not have in vitro
      responses to DENV-SS peptides (mean 144.2 pg/ml) when compared to those who
      responded (mean 75.7 pg/ml). DENV-NS3 specific ex vivo IFNgamma ELISpot responses
      were also significantly lower (p = 0.0001) in those who did not respond to DENV
      SS peptides (mean 42 SFU/million PBMCs) when compared to those who responded to
      DENV-SS peptides (mean 1024 SFU/million PBMCs). Serum IL-10 levels correlated
      significantly (p = 0.03) and inversely (Spearmans R = -0.45) with ex vivo DENV
      NS3 specific responses but not with ex vivo non DENV specific responses
      (Spearmans R = -014, p = 0.52). Blockage of IL-10 in vitro significantly
      increased (p = 0.04) the ex vivo IFNgamma ELISpot DENV-NS3 specific responses but
      had no effect on responses to non DENV proteins. CONCLUSION: IL-10 appears to
      contribute to the pathogenesis of acute dengue infections by inhibiting DENV
      specific T cell responses, which can be restored by blocking IL-10.

PMID- 24040432
TI  - Lymphatic filariasis in Nigeria; micro-stratification overlap mapping (MOM) as a
      prerequisite for cost-effective resource utilization in control and surveillance.
AB  - BACKGROUND: Nigeria has a significant burden of lymphatic filariasis (LF) caused
      by the parasite Wuchereria bancrofti. A major concern to the expansion of the LF
      elimination programme is the risk of serious adverse events (SAEs) associated
      with the use of ivermectin in areas co-endemic with Loa filariasis. To better
      understand this, as well as other factors that may impact on LF elimination, we
      used Micro-stratification Overlap Mapping (MOM) to highlight the distribution and
      potential impact of multiple disease interventions that geographically coincide
      in LF endemic areas and which will impact on LF and vice versa.
      METHODOLOGY/PRINCIPAL FINDINGS: LF data from the literature and Federal Ministry
      of Health (FMoH) were collated into a database. LF prevalence distributions;
      predicted prevalence of loiasis; ongoing onchocerciasis community-directed
      treatment with ivermectin (CDTi); and long-lasting insecticidal mosquito net
      (LLIN) distributions for malaria were incorporated into overlay maps using
      geographical information system (GIS) software. LF was prevalent across most
      regions of the country. The mean prevalence determined by circulating filarial
      antigen (CFA) was 14.0% (n = 134 locations), and by microfilaria (Mf) was 8.2% (n
      = 162 locations). Overall, LF endemic areas geographically coincided with CDTi
      priority areas, however, LLIN coverage was generally low (<50%) in areas where LF
      prevalence was high or co-endemic with L. loa. CONCLUSIONS/SIGNIFICANCE: The
      extensive database and series of maps produced in this study provide an important
      overview for the LF Programme and will assist to maximize existing interventions,
      ensuring cost effective use of resources as the programme scales up. Such
      information is a prerequisite for the LF programme, and will allow for other
      factors to be included into planning, as well as monitoring and evaluation
      activities given the broad spectrum impact of the drugs used.

PMID- 24040433
TI  - Patterns of migration and risks associated with leprosy among migrants in
      Maranhao, Brazil.
AB  - Leprosy remains a public health problem in Brazil with new case incidence
      exceeding World Health Organization (WHO) goals in endemic clusters throughout
      the country. Migration can facilitate movement of disease between endemic and non
      endemic areas, and has been considered a possible factor in continued leprosy
      incidence in Brazil. A study was conducted to investigate migration as a risk
      factor for leprosy. The study had three aims: (1) examine past five year
      migration as a risk factor for leprosy, (2) describe and compare geographic and
      temporal patterns of migration among past 5-year migrants with leprosy and a
      control group, and (3) examine social determinants of health associated with
      leprosy among past 5-year migrants. The study implemented a matched case-control
      design and analysis comparing individuals newly diagnosed with leprosy (n = 340)
      and a clinically unapparent control group (n = 340) without clinical signs of
      leprosy, matched for age, sex and location in four endemic municipalities in the
      state of Maranhao, northeastern Brazil. Fishers exact test was used to conduct
      bivariate analyses. A multivariate logistic regression analysis was employed to
      control for possible confounding variables. Eighty cases (23.5%) migrated 5-years
      prior to diagnosis, and 55 controls (16.2%) migrated 5-years prior to the
      corresponding case diagnosis. Past 5 year migration was found to be associated
      with leprosy (OR: 1.59; 95% CI 1.07-2.38; p = 0.02), and remained significantly
      associated with leprosy after controlling for leprosy contact in the family,
      household, and family/household contact. Poverty, as well as leprosy contact in
      the family, household and other leprosy contact, was associated with leprosy
      among past 5-year migrants in the bivariate analysis. Alcohol consumption was
      also associated with leprosy, a relevant risk factor in susceptibility to
      infection that should be explored in future research. Our findings provide
      insight into patterns of migration to localize focused control efforts in endemic
      areas with high population mobility.

PMID- 24040434
TI  - Ex vivo innate immune cytokine signature of enhanced risk of relapsing
      brucellosis.
AB  - BACKGROUND: Brucellosis, a zoonotic infection caused by one of the Gram-negative
      intracellular bacteria of the Brucella genus, is an ongoing public health problem
      in Peru. While most patients who receive standard antibiotic treatment recover, 5
      40% suffer a brucellosis relapse. In this study, we examined the ex vivo immune
      cytokine profiles of recovered patients with a history of acute and relapsing
      brucellosis. METHODOLOGY/PRINCIPAL FINDINGS: Blood was taken from healthy control
      donors, patients with a history of acute brucellosis, or patients with a history
      of relapsing brucellosis. Peripheral blood mononuclear cells were isolated and
      remained in culture without stimulation or were stimulated with a panel of toll
      like receptor agonists or heat-killed Brucella melitensis (HKBM) isolates. Innate
      immune cytokine gene expression and protein secretion were measured by
      quantitative real-time polymerase chain reaction and a multiplex bead-based
      immunoassay, respectively. Acute and relapse patients demonstrated consistently
      elevated cytokine gene expression and secretion levels compared to controls.
      Notably, these include: basal and stimulus-induced expression of GM-CSF, TNF
      alpha, and IFN-gamma in response to LPS and HKBM; basal secretion of IL-6, IL-8,
      and TNF-alpha; and HKBM or Rev1-induced secretion of IL-1beta, IL-2, GM-CSF, IFN
      Upsilon, and TNF-alpha. Although acute and relapse patients were largely
      indistinguishable by their cytokine gene expression profiles, we identified a
      robust cytokine secretion signature that accurately discriminates acute from
      relapse patients. This signature consists of basal IL-6 secretion, IL-1beta, IL
      2, and TNF-alpha secretion in response to LPS and HKBM, and IFN-gamma secretion
      in response to HKBM. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that
      informative cytokine variations in brucellosis patients can be detected using an
      ex vivo assay system and used to identify patients with differing infection
      histories. Targeted diagnosis of this signature may allow for better follow-up
      care of brucellosis patients through improved identification of patients at risk
      for relapse.

PMID- 24040435
TI  - Sinomenine protects mice against ischemia reperfusion induced renal injury by
      attenuating inflammatory response and tubular cell apoptosis.
AB  - Sinomenine (SIN) is a purified alkaloid from the Chinese herb Sinomenium acutum.
      Previous studies demonstrated that SIN possesses anti-inflammatory and anti
      apoptotic properties. We thus in the present report conducted studies to examine
      its impact on ischemia reperfusion (IR) induced renal injury. Precondition of
      mice with 200 mg/kg of SIN provided significant protection for mice against IR
      induced renal injury as manifested by the attenuated serum creatinine (Cre) and
      blood urea nitrogen (BUN) along with less severity for histological changes and
      tubular cell apoptosis. In line with these results, treatment of mice with SIN
      suppressed IR-induced inflammatory infiltration and the expression of chemokine
      CXCL-10, adhesion molecule ICAM-1, and cytokines TNF-a/IL-6. Mechanistic studies
      revealed that SIN inhibits NF-kappaB transcriptional activity to suppress IR
      induced inflammatory response in the kidney, while it attenuates MAP kinase
      signaling to prevent tubular cells undergoing apoptosis after IR insult.
      Altogether, our data support that SIN could be a useful therapeutic agent for
      prevention and treatment of IR-induced renal injury in the clinical settings. 

PMID- 24040436
TI  - Inflammatory thoracic aortic aneurysm (lymphoplasmacytic thoracic aortitis): a 13
      year-experience at a German Heart Center with emphasis on possible role of IgG4.
AB  - BACKGROUND & AIM: Aortic aneurysms represent one of the major causes of
      cardiovascular surgery. Their etiology varies greatly based on patient's age and
      other clinicopathologic determinants. In addition to common atherosclerotic
      vascular diseases, an inflammatory etiology, in particular IgG4-related disease
      (IgG4-RD) has increasingly emerged as a cause of dissecting inflammatory aortic
      aneurysms (IAA). METHODS: To assess the frequency and types of IAA, we reviewed
      all cases of aortic aneurysms resected at our Erlangen Heart Center during 2000
      2013. RESULTS: 376 patients underwent resection of aortic aneurysms in the study
      period. These are further categorized as ascending aortic aneurysms (45%), aortic
      arch aneurysm (2%), descending aortic aneurysm (3%), type A dissection (46%) and
      type B dissection (4%). Fifteen cases (4%) showed variable lymphoplasmacytic
      inflammation thus qualifying as IAA. Affected were 9 females and 6 males (female
      to male ratio = 1.5:1; age range: 52-80 yrs; mean: 70 yrs; median: 72 yrs). None
      was known to have IgG4-RD and serum IgG4 and/or IgG levels (known in 6 cases)
      were normal. Variable sclerosing lymphoplasmacytic inflammation was seen either
      confined to the adventitia (periaortitis; mainly in males) or extending through
      all layers (mainly in females). A wide range of IgG4 plasma cells (range: 3
      182/HPF; mean: 51/HPF) and IgG4: IgG ratios (range: 0.02 to 0.91; mean: 0.37)
      were detected. All but one of the cases with at least focally transmural
      inflammation showed a higher IgG4: IgG ratios in excess of 0.3 (range, 0.32-0.91;
      median, 0.62). Lymphoid follicle and variable fibrosis were common but
      obliterative phlebitis was not seen. CONCLUSION: IgG4-rich sclerosing
      lymphoplasmacytic thoracic aortitis is a constant histological feature of
      thoracic IAA. Normal serum IgG4 in most patients, predilection for women and
      absence of other features of IgG4-RD all suggest a tissue-specific localized
      autoimmunological process and argue against a systemic disorder. The relationship
      (if any) of IgG4-rich lymphoplasmacytic thoracic aortitis in those patients with
      IAA lacking other organ manifestations or an elevated serum IgG4 level to
      systemic IgG4-RD remains unclear and merit further studies.

PMID- 24040437
TI  - Investigation of splicing changes and post-translational processing of LMNA in
      sporadic inclusion body myositis.
AB  - Some features of sporadic inclusion body myositis (s-IBM) suggest that there is
      acceleration of the normal ageing process in muscle tissue. LMNA encodes the
      nuclear lamina proteins lamin A/C through alternative splicing, and aberrant
      splicing of exon 11 leads to the premature ageing disease, Hutchinson-Gilford
      progeria syndrome. Progerin, the pathogenic isoform expressed in HGPS tissues,
      has also been detected at low levels in tissues of normal individuals with aging.
      We therefore investigated the alternative splicing of LMNA gene transcripts, and
      the post-translational processing of prelamin A, in s-IBM and control muscle
      samples. Age-related low level expression of the progerin transcript was detected
      in both s-IBM and control muscles, but was not increased in s-IBM and there was
      no increase in progerin protein or demonstrable accumulation of intermediate
      prelamin isoforms in the s-IBM muscles. However, an age-related shift in the
      balance of splicing towards lamin A-related transcripts, which was present in
      normal muscles, was not found in s-IBM. Our findings indicate that while there
      are changes in the patterns of LMNA splicing in s-IBM muscle which are probably
      secondary to the underlying pathological process, it is unlikely that aberrant
      splicing of exon 11 or defective post-translational processing of prelamin A are
      involved in the pathogenesis of the disease. 

PMID- 24040438
TI  - Array analysis for potential biomarker of gemcitabine identification in non-small
      cell lung cancer cell lines.
AB  - Gemcitabine is one of the most widely used drugs for the treatment of advanced
      Non-small cell lung cancer (NSCLC), but modest objective response rate of
      patients to gemcitabine makes it necessary to identify novel biomarkers for
      patients who can benefit from gemcitabine-based therapy and to improve the effect
      of clinical therapy. In this work, 3 NSCLC cell lines displaying different
      sensitivities to gemcitabine were applied for mRNA and microRNA (miR) expression
      chips to figure out the biomarkers for gemcitabine sensitivity. Genes whose
      expression increased dramatically in sensitive cell lines were mainly enriched in
      cell adhesion (NRP2, CXCR3, CDK5R1, IL32 and CDH2) and secretory granule
      (SLC11A1, GP5, CD36 and IGF1), while genes with significantly upregulated
      expression in resistant cell line were mainly clustered in methylation
      modification (HIST1H2BF, RAB23 and TP53) and oxidoreductase (TP53I3, CYP27B1 and
      SOD3). The most intriguing is the activation of Wnt/beta-catenin signaling in
      gemcitabine resistant NSCLC cell lines. The miR-155, miR-10a, miR-30a, miR-24-2*
      and miR-30c-2* were upregulated in sensitive cell lines, while expression of miR
      200c, miR-203, miR-885-5p, miR-195 and miR-25* was increased in resistant cell
      line. Genes with significantly altered expression and putatively mediated by the
      expression-changed miRs were mainly enriched in chromatin assembly (MAF, HLF,
      BCL2, and IGSF3), anti-apoptosis (BCL2, IGF1 and IKBKB), protein kinase (NRP2,
      PAK7 and CDK5R1) (all the above genes were upregulated in sensitive cells) and
      small GTPase mediated signal transduction (GNA13, RAP2A, ARHGAP5 and RAB23, down
      regulated in sensitive cells). Our results might provide potential biomarkers for
      gemcitabine sensitivity prediction and putative targets to overcome gemcitabine
      resistance in NSCLC patients. 

PMID- 24040439
TI  - The differential expression of TGF-beta1, ILK and wnt signaling inducing
      epithelial to mesenchymal transition in human renal fibrogenesis: an
      immunohistochemical study.
AB  - Epithelial-to-mesenchymal transition (EMT) is a process for fully differentiated
      epithelial cells to undergo a phenotypic change to fibroblasts via diverse
      intracellular signaling pathways. While the pivotal role of fibroblasts in renal
      fibrosis is widely accepted, their origin remains undefined. In addition,
      although a large number of studies have provided evidence of EMT in human kidney
      diseases, specific signaling pathways leading to EMT have not yet been discovered
      in humans. To evaluate the origin of interstitial fibroblasts and signaling
      pathways involved in the EMT process, we analyzed the differential expression of
      EMT-related molecules in paraffin-fixed sections from 19 human fibrotic kidneys
      and 4 control kidneys. In human fibrotic kidneys, tubular epithelial cells (TECs)
      with intact tubular basement membrane (TBM) showed loss or down-regulation of an
      epithelial marker (E-cadherin), de novo expression of mesenchymal markers
      (vimentin and fibronectin), and significant up-regulation of inducers and
      mediators controlling the EMT process (transforming growth factor-beta1 (TGF
      beta1), p-Smad2/3, beta1-integrin, p38 mitogen-activated protein kinase (MAPK),
      WNT5B and beta-catenin) in the areas of interstitial inflammation and fibrosis,
      compared with their expression in control kidneys. In conclusion, the type II EMT
      process in humans is thought to be an adaptive response of TECs to chronic injury
      and is regulated by interconnections of TGF-beta/Smad, integrin/integrin-linked
      kinase (ILK) and wnt/beta-catenin signaling pathways. 

PMID- 24040440
TI  - Limited therapeutic efficacy of thrombopoietin on the regeneration of steatotic
      livers.
AB  - Liver regeneration after partial hepatectomy is impaired in steatotic livers of
      leptin-deficient ob/ob mice. Previous studies have shown that thrombopoietin
      (TPO) promotes liver regeneration and improves liver cirrhosis by an increase of
      platelet counts and the expansion of hepatic progenitor cells. Herein we studied
      whether TPO exerts pro-proliferative and hepatoprotective effects and thereby
      improves the regenerative capacity of steatotic livers. For this purpose, we
      studied hepatic regeneration at day 2, 3, 7 and 10 in a model of 55% hepatectomy
      in obese (ob/ob) and non-obese (C57BL/6J) mice. Liver function and injury,
      platelet counts, weight of the regenerated liver, proliferating liver cells as
      well as the number of hepatic (CK19-positive) oval cells were quantified by
      biochemical and immunohistochemical analysis. As expected, obese mice had a
      markedly decreased regenerative capacity of livers compared with lean animals.
      Pretreatment of mice with recombinant TPO (12.5 MUg/kg) had no evident effect on
      regeneration of fatty livers, but ameliorated acute liver damage in obese mice,
      as indicated by decreased liver enzyme release early after resection. TPO was
      unable to enhance hepatocyte proliferation, but increased proliferation of non
      parenchymal cells, including CK19-positive oval cells, at later observation time
      points after resection. Interestingly, TPO completely inhibited the resection
      induced increase of plasma triglycerides immediately after resection in non-obese
      mice. In conclusion, TPO slightly prevents acute liver damage after resection in
      obese mice, but fails to significantly enhance regeneration of fatty livers. 

PMID- 24040441
TI  - AMPK activity is down-regulated in endothelial cells of GHS-R(-/-) mice.
AB  - Ghrelin/GHS-R axis is known as its role in stimulating growth hormone release.
      Besides, it is also implicated in the regulation of atherosclerosis (AS), a
      chronic vascular disease that has been recognized as the main cause of coronary
      heart disease and cerebrovascular disease. It has been reported that both Ghrelin
      and AMPK play protective roles in AS by inhibiting the inflammatory response as
      well as cell proliferation. However, it remains unclear whether AMPK pathway is
      involved in Ghrelin/GHS-R-mediated inhibition of the inflammatory response and
      cell proliferation in AS. Here, we established the GHS-R gene knockout mice (GHS
      R(-/-)) and found that AMPK activity is notably down-regulated in endothelial
      cells (ECs) of GHS-R(-/-) mice and the ECs from GHS-R(-/-) mice possess higher
      proliferative capability than the ECs from wild-type mice. Moreover, AMPK is
      activated in primary ECs upon Ghrelin induction in vitro. Taking together, the
      present study unravels that Ghrelin/GHS-R could efficiently activate AMPK in ECs,
      suggesting a possible mechanism that the roles of Ghrelin/GHS-R in the inhibition
      of inflammatory response and cell proliferation in AS disease may be partially
      mediated by activating AMPK. 

PMID- 24040442
TI  - IL-22 secreted by decidual stromal cells and NK cells promotes the survival of
      human trophoblasts.
AB  - Interleukin-22 (IL-22) has been implicated as an important immune regulator in
      many physiologic and pathological processes, but little is known about the IL-22
      in the fetal-maternal interface. In this study, we demonstrated that co-culture
      of decidual stromal cells (DSCs) and decidual natural killer (dNK) cells resulted
      in increased secretion of IL-22, compared to culture of DSCs or dNK cells alone.
      The trophoblast cell line, HTR8/SVneo, expresses IL-22 receptor alpha1 (IL-22R1).
      Combinant human (rh) IL-22 significantly promoted the proliferation and
      viability, and inhibited the apoptosis of HTR8/SVneo cells. By Western blotting
      and immunohistochemistry, we confirmed that villi expressed IL-22R1, and the
      villi from unexplained spontaneous miscarriage patients expressed reduced levels
      of IL-22R1 than those from normal early pregnancy. These findings indicate that
      the IL-22 secreted by DSCs and dNK might promote the survival of trophoblasts and
      participate in the maintenance of pregnancy by binding to the IL-22R1. The
      reduced level of IL-22/IL-22R1 in villi might be involved in the occurrence of
      spontaneous miscarriage. 

PMID- 24040443
TI  - Expression of dishevelled gene in Hirschsprung's disease.
AB  - Hirschsprung's disease (HSCR) is a congenital disorder of the enteric nervous
      system and is characterized by an absence of enteric ganglion cells in terminal
      regions of the gut during development. Dishevelled (DVL) protein is a cytoplasmic
      protein which plays pivotal roles in the embryonic development. In this study, we
      explore the cause of HSCR by studying the expression of DVL-1 and DVL-3 genes and
      their proteins in the aganglionic segment and the ganglionic segment of colon in
      HSCR patients. MATERIALS AND METHODS: Specimen of aganglionic segment and
      ganglionic segment of colon in 50 cases of HSCR patients. Expression levels of
      mRNA and proteins of DVL-1 and DVL-3 were confirmed by quantitative real-time PCR
      (qRT-PCR), western blot and immunohistochemistry staining between the aganglionic
      segment and the ganglionic segment of colon in HSCR patients. RESULTS: The mRNA
      expression of DVL-1 and DVL-3 were 2.06 fold and 3.12 fold in the aganglionic
      segment colon tissues compared to the ganglionic segment, respectively.
      Similarly, the proteins expression of DVL-1 and DVL-3 were higher (39.71 +/- 4.53
      vs and 53.90 +/- 6.79 vs) in the aganglionic segment colon tissues than in the
      ganglionic segment (15.01 +/- 2.66 and 20.13 +/- 3.63) by western blot. Besides,
      immunohistochemical staining showed that DVL-1 and DVL-3 have a significant
      increase in mucous and submucous layers from aganglionic colon segments compared
      with ganglionic segments. CONCLUSION: The study showed an association of DVL-1
      and DVL-3 with HSCR, it may play an important role in the pathogenesis of HSCR.

PMID- 24040444
TI  - Growth inhibitory effect of Cucurbitacin E on breast cancer cells.
AB  - OBJECTIVE: Due its inhibitory effects on chemical carcinogenesis and
      inflammation, Cucurbitacins have been proposed as an effective agent for the
      prevention or treatment of human cancers. In this study, we aimed to explore the
      effect of Cucurbitacin E (CuE) on human breast cancer cells. METHODS: The
      inhibitory effect of CuE on proliferation of Bcap37 and MDA-MB-231 cells was
      assessed by MTT assay. The cell cycle distribution and cell apoptosis were
      determined by flow cytometry (FCM). The expression of pro-caspase 3, cleaved
      caspase 3, p21, p27 and the phosphorylation of signaling proteins was detected by
      Western Blotting. RESULTS: CuE inhibited the growth of human breast cancer cells
      in a dose and time-dependent manner. FCM analysis showed that CuE induced G2/M
      phase arrest and cell apoptosis. CuE treatment promoted the cleavage of caspase 3
      and upregulated p21 and p27. In addition, the phosphorylation of STAT3 but not
      ERK-1/2 was abrogated upon CuE treatment. Interestingly, losedose CuE
      significantly enhanced the growth inhibition induced by cisplatin. Conclusions
      Cucurbitacin E (CuE) could inhibit the growth of human breast cancer cells in
      vitro. CuE induced both apoptosis and cell cycle arrest probably through the
      inhibition of STAT3 function. Lose-dose CuE significantly enhanced the growth
      inhibitory effect of cisplatin on breast cancer cells, further indicating the
      potential clinical values of CuE for the prevention or treatment of human breast
      cancer.

PMID- 24040445
TI  - Assessing the role of IL-35 in colorectal cancer progression and prognosis.
AB  - Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact
      impact on colorectal cancer (CRC) progression and prognosis, however, is yet to
      be elucidated clearly. We thus in the present report conducted comparative
      analysis of IL-35 levels between CRC patients and matched control subjects. IL-35
      is highly expressed in all CRC tissues, which can be detected in vast majority of
      colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly
      correlated to the severity of malignancy and the clinical stage of tumor.
      Particularly, a significant reduction for serum IL-35 was noted in patients after
      surgical resection, indicating that IL-35 promotes CRC progression associated
      with poor prognosis. Mechanistic study demonstrated a significant correlation
      between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells
      in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by
      inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells
      into the tumor microenvironment in favor of tumor growth. Together, our data
      support that IL-35 could be a valuable biomarker for assessing CRC progression
      and prognosis in clinical settings. 

PMID- 24040446
TI  - Cellular retinol binding protein 1 could be a tumor suppressor gene in cervical
      cancer.
AB  - AIMS: Cervical Cancer (CC) is one of the most important health problems in women.
      It frequently presents genetic changes at chromosome region 3q21. This region
      contains the Cellular Retinol Binding Protein 1 gene (CRBP1) which has been
      implicated as an important element in the development of other types of cancer.
      The main goal of the present work was to determine the molecular alterations of
      CRBP1 and its relationship to CC. METHODS: To determine the molecular alterations
      of CRBP1 gene in CC; twenty-six CC and twenty-six healthy cervix samples were
      evaluated for: 1) Copy number gain by real-time PCR analysis, 2) expression
      levels by an immunohistochemistry assay on tissue microarray, and 3) the
      methylation status of the CRBP1 promoter region. RESULTS: The increase in CRBP1
      copy number was observed in 10 out of the 26 CC samples analyzed, while healthy
      cervices samples showed no changes in the copy number. In addition, there was a
      lack of expression of the CRBP1 gene in an important number of the CC samples
      (17/26), and the CRBP1 gene promoter was methylated in 15/26 of the CC samples.
      Interestingly, there was a significant association between the lack of expression
      of the CRBP1 gene and its methylation status. CONCLUSIONS: The data indicates
      that, both activating and inactivating changes in the CRBP1 gene could be
      significant events in the development and progression of CC, and the lack of
      expression of the CRBP1 protein could be related with to the development of CC.
      We believe that there is enough evidence to consider to CRBP1 gene as a tumor
      suppressor gene for CC.

PMID- 24040447
TI  - miRNA-9 expression is upregulated in the spinal cord of G93A-SOD1 transgenic
      mice.
AB  - The pathogenesis of amyotrophic lateral sclerosis (ALS) remains unclear.
      Accumulating evidence indicates that various miRNAs expressed in a spatially and
      temporally controlled manner in the nervous system have an important function in
      the development of neurodegenerative diseases. The present study aimed to
      determine the expression and cellular distribution of miRNA-9 in the spinal cord
      of G93A-SOD1 mutant mice at different time points (post-natal 95, 108 and 122 d).
      miRNA expression was evaluated by microarray analysis; differentially expressed
      miRNAs were validated by RT-qPCR. The cellular distribution of miRNA-9 was
      analyzed by in-situ hybridization. Microarray results indicated for the first
      time that various miRNAs were differentially expressed between the G93A-SOD1
      mutant mice and the littermate control mice. miRNA-9 expression was upregulated
      at 95, 108, and 122 d as validated by microarray analysis, RT-qPCR, and ISH. ISH
      results also showed that the miRNA-9-positive cells mainly expressed in the
      cytoplasm were located in the dorsal horn and the ventral horn of the spinal
      cord. The majority of miRNA-9-positive cells were located in the ventral horn of
      the gray matter, the locus of neurodegeneration. These results indicated that the
      differential expression of miRNA-9 may have an important function in the
      pathogenesis of G93A-SOD1 transgenic mice. 

PMID- 24040448
TI  - Value of epithelioid morphology and PDGFRA immunostaining pattern for prediction
      of PDGFRA mutated genotype in gastrointestinal stromal tumors (GISTs).
AB  - AIMS: Genotyping is a prerequisite for tyrosine kinase inhibitor therapy in high
      risk and malignant GIST. About 10% of GISTs are wild-type for KIT but carry
      PDGFRA mutations. Applying the traditional approach, mutation analysis of these
      cases is associated with higher costs if all hotspots regions in KIT (exon 9, 11,
      13, 17) are performed at first. Our aim was to evaluate the predictive value of a
      combined histomorphological-immunohistochemical pattern analysis of PDGFRA
      mutated GISTs to efficiently direct KIT and PDGFRA mutation analysis. METHODS:
      The histomorphology and PDGFRA immunostaining pattern was studied in a test
      cohort of 26 PDGFRA mutants. This was then validated on a cohort of 94 surgically
      resected GISTs with mutations in KIT (n=72), PDGFRA (n=15) or with wild-type
      status (n=7) on a tissue microarray. The histological subtype (spindled,
      epithelioid, mixed), PDGFRA staining pattern (paranuclear dot-like/Golgi,
      cytoplasmic and/or membranous), and extent of staining were determined without
      knowledge of the genotype. The combination of histomorphology and immunophenotype
      were used to classify tumors either as PDGFRA- or non-PDGFRA phenotype. RESULTS:
      PDGFRA-mutated GISTs were significantly more often epithelioid (p<0.001) and had
      a higher PDGFRA expression, compared to KIT-mutants (p<0.001). Paranuclear PDGFRA
      immunostaining was almost exclusively observed in PDGFRA mutants (p<0.001). The
      sensitivity and specificity of this combined histological-immunohistochemical
      approach to predict the PDGFRA-genotype was 100% and 99%, respectively (p=6x10(
      16)). CONCLUSION: A combination of histomorphology and PDGFRA immunostaining is a
      reliable predictor of PDGFRA genotype in GIST. This approach allows direct
      selection of the "gene/exons of relevance" to be analyzed and may help to reduce
      costs and work load and shorten processing time of GIST genotyping by mutation
      analysis.

PMID- 24040449
TI  - FIZZ1 could enhance the angiogenic ability of rat aortic endothelial cells.
AB  - Found in inflammatory zone (FIZZ1), also known as hypoxia-induced mitogenic
      factor (HIMF), is a secreted protein formed by 111 amino acid residues. FIZZ1 is
      mainly located in alveolar epithelial cells, white adipose tissue and the heart.
      This study aimed to explore the effects of FIZZ1 on the angiogenic ability of
      cultured rat aortic endothelial cells (RAECs) and the potential mechanism. The
      RAECs were cultured in the extracellular matrix (ECM) supplemented with 10% fetal
      bovine serum (FBS). Matrigel assay was used to detect the angiogenic ability of
      the RAECs and Agilent Rat Microarray containing 41,000 genes/ESTs was used to
      screen the differentially expressed genes of the RAECs after they were treated
      with FIZZ1 (5 x 10(-9)~2 x 10(-8) mol/L). The results were verified using RT-PCR
      method. We found that FIZZ1 markedly enhanced the angiogenic ability of RAECs
      (22.6 +/- 2.94 vs. 19.7 +/- 2.57, P < 0.01; 28.5 +/- 3.32 vs. 19.7 +/- 2.57, P <
      0.01; 36.9 +/- 5.01 vs. 19.7 +/- 2.57, P < 0.01) in a dose-dependent manner (5 x
      10(-9)~2 x 10(-8) mol/L). 440 genes (Gng8, Atg9a, Gdf6, etc.) were found to be up
      regulated and 497 genes (Hbb-b1, Camk1g, etc.) down-regulated in the experimental
      group. Changes in Gng8 and Atg9a were revealed by RT-PCR. FIZZ1 could enhance
      angiogenesis of RAECs by up-regulating Gng8 and Atg9a. 

PMID- 24040450
TI  - Increased expression of EphA1 protein in prostate cancers correlates with high
      Gleason score.
AB  - The erythropoietin-producing hepatocellular (Eph) family of receptor tyrosine
      kinases regulates a multitude of physiological and pathological processes. EphA1
      is the first member of Eph superfamily and is involved in carcinogenesis. The aim
      of this study was to investigate the expression of EphA1 in prostate cancers cell
      lines and the tissues, then explore the correlation with the clinicopathologic
      parameters. The EphA1 transcript expression in prostate cancer cell lines was
      detected by Quantitative real-time PCR. The expression of EphA1 protein in 138
      prostate cancer tissue samples and 21 benign prostate hyperplasia samples were
      checked by using immunohistochemical staining. EphA1 mRNA was high expressed in
      LNCap, moderately expressed in 22RV1 and Du145, and lost in PC3. Loss of
      expression of EphA1 transcript was related to hypermethylation of CpG island
      around the translation start site. EphA1 protein was differentially expressed in
      prostate cancers and hyperplasia. Increased expression of EphA1 protein was more
      frequently detected in prostate cancers than in hyperplasia (P = 0.02), and more
      often detected in prostate cancer with high Gleason score (P < 0.001). Our data
      indicate that EphA1 receptor may have roles in carcinogenesis and progression of
      prostate cancer, and can be a potentially useful target for prognostic and
      therapeutic application. 

PMID- 24040451
TI  - Immunochemiluminescent detection of galectin-3 in tumoral tissue from prostate.
AB  - This work proposes a chemiluminescent quantitative method for galectin-3 (Gal3)
      detection in prostate tissues. Monoclonal antibody anti-Gal3 was conjugated to
      acridinium ester (AE) and the complex formed with Gal3 in the prostate tissue was
      chemiluminescently detected. The light emission (expressed in Relative Light Unit
      RLU) showed mean values higher for benign prostatic hyperplasia than normal
      tissues and adenocarcinoma. These differences showed to be statistically
      significant (p < 0.001). There was a linear relationship between RLU and tissue
      area. Furthermore, these values were dramatically reduced when the tissue samples
      were previously incubated with non labeled anti-Gal3. Finally, the anti-Gal3-AE
      solution in buffer stored at 4 degrees C and the treated samples showed to be
      stable during a year and at least 72 h, respectively. Gal3 content in prostate
      tissue was higher in benign prostatic hyperplasia than normal tissues and much
      lower in adenocarcinoma. This quantitative, specific and sensitive method based
      on labeling antibody to acridinium ester can be applied to detect antigen in
      tissue. 

PMID- 24040452
TI  - Pigmented squamous intraepithelial neoplasia of the esophagus.
AB  - Squamous cell carcinoma (SCC) usually lacks melanocytes within the tumor. A few
      reports have documented invasive SCC or SCC in situ (intraepithelial neoplasia,
      IEN) with melanocytic hyperplasia within the tumor, referred to as pigmented SCC,
      in some organs. However, case series of pigmented SCC or IEN of the esophagus
      have not yet been reported. This is the first study to analyze the incidence and
      clinicopathological features of pigmented SCC or IEN of the esophagus. We
      reviewed 18 surgically-resected and 122 endoscopically-resected esophageal
      specimens, including 79 cases of IEN. Three cases of pigmented IEN were observed
      in this series, and all of them were located in the middle to lower third of the
      esophagus. Two of 3 cases had melanocytosis in the non-neoplastic squamous
      epithelium around the IEN. The incidence of pigmented IEN was 2.5% of all
      endoscopically resected specimens and 3.8% of IEN cases. No pigmented invasive
      SCC was detected in both endoscopically-resected and surgically-resected
      specimens. The mechanism of pigmentation of esophageal IEN is unknown. However,
      production of melanocyte chemotactic factors by tumor cells has been demonstrated
      in pigmented SCC of the oral mucosa. Moreover, two of 3 cases of pigmented IEN in
      the present series had melanocytosis in the non-neoplastic squamous epithelium,
      and melanocytosis is thought to be associated with chronic esophagitis,
      therefore, it has been hypothesized that various stimuli can cause pigmentation
      in squamous epithelium. Additional studies are needed to clarify the mechanism of
      pigmentation in squamous IEN of the esophagus. 

PMID- 24040453
TI  - Immunohistochemical evaluation of cardiac connexin43 in rats exposed to low
      frequency noise.
AB  - INTRODUCTION: Low-frequency noise (LFN) leads to an abnormal proliferation of
      collagen and development of tissue fibrosis. It has been shown that myocardial
      fibrosis in association with gap junction remodeling occurs in several cardiac
      diseases and can be implicated in the development of ventricular
      tachyarrhythmias. We previously reported a strong development of myocardial
      fibrosis induced by LFN in rats but it is not known whether LFN induces any
      modification on cardiac connexin43 (Cx43). OBJECTIVES: The aim of this study was
      to evaluate modifications on cardiac Cx43 induced by LFN in Wistar rats. METHODS:
      Two groups of rats were considered: A LFN-exposed group with 10 rats submitted
      continuously to LFN during 3 months and a control group with 8 rats. The hearts
      were sectioned from the ventricular apex to the atria and the mid-ventricular
      fragment was selected. The immunohistochemical evaluation of Cx43 was performed
      using the polyclonal antibody connexin-43m diluted 1:1000 overnight at 4 degrees
      C. Quantifications of Cx43 and muscle were performed with the image J software
      and the ratio Cx43/muscle was analyzed in the left ventricle, interventricular
      septum and right ventricle. RESULTS: The ratio Cx43/muscle was significantly
      reduced in LFN-exposed rats (p=0.001). The mean value decreased 46.2%, 22.2% and
      55.6% respectively in the left ventricle (p=0.008), interventricular septum
      (p=0.301) and right ventricle (p=0.004). CONCLUSIONS: LFN induces modifications
      on cardiac Cx43 in rats. The Cx43 reduction observed in our study suggests that
      LFN may induce an arrhythmogenic substrate and opens a new investigational area
      concerning the effects of LFN on the heart.

PMID- 24040454
TI  - Screening for EGFR and KRAS mutations in non-small cell lung carcinomas using DNA
      extraction by hydrothermal pressure coupled with PCR-based direct sequencing.
AB  - EGFR and KRAS mutations correlate with response to tyrosine kinase inhibitors in
      patients with non-small cell lung carcinoma (NSCLC). We reported a hydrothermal
      pressure method of simultaneous deparaffinization and lysis of formalin-fixed
      paraffin embedded (FFPE) tissue followed by conventional chaotropic salt column
      purification to obtain high quality DNA for mutation analysis using PCR-base
      direct sequencing. This study assessed the feasibility of using this method to
      screen for exons 18-21 of EGFR and exon 2 of KRAS gene mutations in surgical
      resection and core needle biopsy specimens from 251 NSCLC patients. EGFR
      mutations were identified in 140 (55.8%) NSCLC patients (118 in adenocarcinoma,
      11 in squamous cell carcinoma, 7 in adenocarcinoma and 4 in NSCLC-not otherwise
      specified), including four novel substitutions (L718M, A743V, L815P, V819E). EGFR
      mutations were frequently present in female patients (72 of 113, 63.7%) and NSCLC
      with adenocarcinoma component (125/204, 61.3%) with statistical significance.
      Twenty-one patients had multiple mutations at different exons of EGFR, in which
      seventeen patients had deletions in exon 19. KRAS mutations were found in 18
      (7.2%) patients (15 in adenocarcinoma, 2 in squamous cell carcinoma and one in
      NSCLC-not otherwise specified), including an uncommon substitution G13C.
      Deparaffinization and lysis by hydrothermal pressure, coupled with purification
      and PCR-based sequencing, provides a robust screening approach for EGFR and KRAS
      mutation analysis of FFPE tissues from either surgical resection or core needle
      biopsy in clinical personalized management of lung cancer. 

PMID- 24040455
TI  - Pigmented pilomatricoma: an underrecognized variant.
AB  - The presence of melanin pigment and/or melanocytes in pilomatricoma has been
      rarely documented. In this study, we analyzed the incidence and
      clinicopathological features of pigmented pilomatricoma. Fifty-seven consecutive
      pilomatricoma cases from 53 Japanese patients were examined in this study. In
      fourteen cases (24.6%), pigmentation was observed in pilomatricoma. This variant
      equally affected in males and females, and the common locations were the upper
      arm and face. Proliferation of dendritic melanocytes was observed within basaloid
      cell nests in all cases, and melanin pigment was also present within the
      cytoplasm of the basaloid cells in 11 cases. Melanin pigment was also present in
      the shadow cells in 7 cases. The incidence of pigmented pilomatricoma as
      documented in previous reports is approximately 10%. However, our analysis
      revealed that pigmented pilomatricoma was found in 24.6% of Japanese cases of
      pilomatricoma, thus, this variant is not uncommon and may be under-recognized. 

PMID- 24040456
TI  - The association of Pro12Ala polymorphism in the peroxisome proliferator-activated
      receptor-gamma2 gene with the metabolic characteristics in Chinese women with
      polycystic ovary syndrome.
AB  - BACKGROUND: The Pro12Ala polymorphism in the peroxisome Proliferator-activated
      receptor-gamma2 PPARgamma2) gene that account for metabolic dysfunction in women
      with polycystic ovary syndrome (PCOS) remain elusive. AIM: To explore the
      association between PPARgamma2 gene pro12ala polymorphism and the metabolic
      characteristics in Chinese women with PCOS. METHODS: PPARgamma2 gene Pro12Ala
      polymorphism was assayed by PCR/RFLP methods in 120 Chinese women with PCOS and
      118 normal subjects. All subjects were examined by anthropometry, lipid profile,
      sex hormone, oral glucose tolerance tests and insulin tolerance tests. RESULTS:
      In PCOS patients, women with the non-Pro/Pro genotypes of the PPARgamma2 gene
      Pro12Ala polymorphism showed statistically significantly higher fasting
      triglycerides (TG) levels and WHR value than those with the Pro/Pro genotype
      (P=.006 for both). There was no significant difference with PPARgamma2 Pro12Ala
      polymorphism distributions between Chinese Han women with PCOS and controls.
      CONCLUSION: PPARgamma2 gene Pro12Ala polymorphism was not supposed to be
      susceptible genes in PCOS. However, in PCOS patients, the PPAR-gamma Pro12Ala
      polymorphism may modulate the concentrations of serum fasting TG levels and fat
      deposition in abdomen, respectively.

PMID- 24040457
TI  - Comparison of the GnRH agonist and antagonist protocol on the same patients in
      assisted reproduction during controlled ovarian stimulation cycles.
AB  - Despite the fact that both gonadotropin-releasing hormone (GnRH) agonist and
      antagonist protocol are effective in suppressing the incidence of premature
      luteinizing hormone (LH) surges through reversibly blocking the secretion of
      pituitary gonadotropins, the exact impact of these two distinctive protocols on
      the clinical setting of patients for in vitro fertilization and embryo transfer
      (IVF-ET) treatment, however, remained controversial. We thus in the present
      report conducted a retrospective study to compare the impact of GnRH agonist and
      antagonist protocol on the same patients during controlled ovarian stimulation
      cycles. A total of 81 patients undergoing 105 agonist and 88 antagonist protocol
      were analyzed. We failed to detect a significant difference between two protocols
      for the difference in duration of ovarian stimulation, number of recombinant FSH
      (Gonal-F) ampoules used, number of oocytes retrieved, serum levels for estradiol
      (E2) and progestone (P), thickness of endometrium, and the zygote- and blastocyst
      development rate. It is seemly that high quality embryo rate was higher in the
      antagonist protocol, but the data did not reach a statistical significance.
      Nevertheless, Implantation rate and clinical pregnancy rate were significantly
      higher in the antagonist protocol (10.64% and 30.26%, respectively) than that of
      the agonist protocol (5.26% and 15.82%, respectively). Our data also suggest that
      the GnRH antagonist protocol is likely to have the advantage for improving the
      outcome of pregnancy in those patients with a history of multiple failures for
      the IVF-ET treatment. 

PMID- 24040458
TI  - The impact of endometriosis on IVF/ICSI outcomes.
AB  - This retrospective cohort study was aimed to investigate the impact of
      endometriosis on the IVF/ICSI outcomes. A total of 1027 cycles of patients
      undergoing IVF/ICSI treatment in a reproductive medicine unit of academic
      hospital were enrolled. In the present study, 431 cycles of patients with
      endometriosis constituted the study group, including 152 cycles of patients with
      stage I-II endometriosis and 279 cycles of patients with stage III-IV
      endometriosis, while 596 cycles of patients with tubal factors infertility were
      considered as the control group. Ovarian stimulation parameters and IVF/ICSI
      outcomes were compared. Patients with stage I-II and stage III-IV endometriosis
      required higher dosage and longer duration of gonadotropins, but had lower day 3
      high-quality embryos rate, when compared to patients with tubal infertility. In
      addition, the number of oocytes retrieved, the number of obtained embryos, the
      number of day 3 high-quality embryos, serum E2 level on the day of hCG,
      fertilization rate were lower in patients with stage III-IV endometriosis than
      those in tubal factors group. Except reduced implantation rate in stage III-IV
      endometriosis group, no differences were found in other pregnancy parameters.
      This study suggests that IVF/ICSI yielded similar pregnancy outcomes in patients
      with different stages of endometriosis and patients with tubal infertility.
      Therefore, IVF/ICSI can be considered as an effective approach for managing
      endometriosis-associated infertility. 

PMID- 24040459
TI  - Primary sacral non-germinal center type diffuse large B-cell lymphoma with MYC
      translocation: a case report and a review of the literature.
AB  - An 85-year-old man presented with pain and numbness in the left buttock, and
      physical examination revealed an approximately 7 cm mass extending from the first
      to the third sacral vertebrae; biopsy of the mass led to the diagnosis of CD10
      negative, BCL6-weakly positive, MUM1-positive, non-germinal center (non-GC) type
      diffuse large B-cell lymphoma (DLBCL). Furthermore, serological testing showed
      negative results for Epstein-Barr virus (EBV) infection, and fluorescence in situ
      hybridization (FISH) revealed a MYC translocation. Radiographs showed no
      remarkable osteolytic bone destruction, and the patient was staged with Stage
      IAE. After 8 cycles of rituximab therapy and 6 cycles of CHOP therapy, complete
      remission has been maintained until now, approximately 1 year after the
      treatment. Primary sacral lymphoma is very rare, with only 6 reported cases,
      including the present one. A review of the reported cases revealed that the
      disease predominantly affects elderly men, is usually non-GC-type DLBCL and stage
      IAE, measures approximately 2-7 cm in diameter in general, and does not show
      early recurrence after chemotherapy or chemoradiotherapy. There is no report in
      the literature yet of primary sacral DLBCL with MYC translocation, and this is
      the first case report. On the other hand, 35 cases of CD10-negative DLBCL with
      MYC translocation, including the present one, have been reported, and a review of
      the reported cases showed that the disease predominantly affects Asians, middle
      aged or elderly men, shows positivity for either BCL6 or MUM1 and negativity for
      EBV, and has a high international prognostic index and poor prognosis. 

PMID- 24040460
TI  - Primary ductal adenocarcinoma of the lacrimal sac: the first reported case.
AB  - Primary lacrimal sac tumor is extremely rare, and moreover, glandular tumor is
      exceptional. Herein, we described the first documented case of primary ductal
      adenocarcinoma of the lacrimal sac. A 79-year-old Japanese female presented with
      persistent swelling of her left lower eyelid. Computed tomography demonstrated an
      irregular-shaped tumor involving the left lacrimal sac, lower eyelid, sinonasal
      tract, and internal side of the left orbit. Biopsy from the eyelid revealed a
      poorly differentiated adenocarcinoma. Histopathological study of the resected
      lacrimal sac tumor revealed an infiltrative neoplastic growth that was composed
      of cribriform structures with comedonecrosis. The neoplastic cells had relatively
      rich granular eosinophilic cytoplasm and large round to oval nuclei containing
      conspicuous nucleoli. The left cervical lymph nodes had metastatic carcinoma.
      Immunohistochemically, the neoplastic cells were diffusely positive for gross
      cystic disease fluid protein-15 and androgen receptor. Moreover, mammalian target
      of rapamycin (mTOR), 4E-BP1, and p4E-BP1 were expressed. According to these
      results, an ultimate diagnosis of primary ductal adenocarcinoma of the lacrimal
      sac was made. Only 9 cases of primary lacrimal sac adenocarcinoma have been
      reported, and this is the first reported case of ductal adenocarcinoma of the
      lacrimal sac. Ductal adenocarcinoma of the salivary gland shows an aggressive
      clinical course, and the present case had multiple cervical lymph node
      metastases. This report is the first to demonstrate that mTOR pathway proteins,
      which are central proteins involved in carcinogenesis, are activated in ductal
      adenocarcinoma. Therefore, mTOR inhibitor may be a potential candidate for
      treatment of this highly aggressive carcinoma. 

PMID- 24040461
TI  - Composite hemangioendothelioma arising from the kidney: case report with review
      of the literature.
AB  - Reported herein is a medical curiosities vascular tumor primary arising from the
      kidney and exhibiting unique histopathological features. A 32-year-old woman
      underwent a total nephrectomy of right kidney because of a mass localized in the
      inferior pole. Distinct from other vascular lesions, on histology the tumor had a
      peculiar composite pattern, consisting of benign and malignant vascular
      components, which were haphazardly intermixed without any definite margins. The
      malignant component was composed of epithelioid hemangioendothelioma (45%) and
      angiosarcoma (50%) with moderate differentiation. Immunohistochemically, the oval
      to cuboidal to spindle tumor cells expressed only endothelial markers (CD31, CD34
      and factor VIII-related antigen). And the angiosarcomatous component was
      characterized by the presence of a greater proliferation index Ki-67. Unlike
      other epithelial tumors, smooth muscle actin (SMA), cytokeratin, EMA and S-100
      were all negative in the epithelioid tumor cells. These findings led to the
      diagnosis of a low-grade vascular neoplasm with morphological features consistent
      with so-called composite hemangioendothelioma (CHE). At 11 month follow up the
      patient was alive, without evidence of tumor recurrence. CHE is an extremely rare
      vascular neoplasm, with borderline malignant potential, which mostly occurs in
      distal extremity of the limbs at the cutaneous level and, only 30 cases have been
      previously described until now. To our knowledge, this is the first report of CHE
      arising from the kidney and widens the spectrum of primary vascular tumors
      arising in the kidney. 

PMID- 24040462
TI  - Endobronchial metastasis from hepatocellular carcinoma - a case description with
      literature review.
AB  - Endobronchial metastases from hepatocellular carcinoma are very rare. Up to date,
      no more than 7 cases were reported. The authors present a case of 20-year old
      female with metastatic hepatocellular carcinoma to superior lobar bronchus.
      Examination of cytological and small biopsy specimens obtained from bronchoscopy
      revealed characteristic microscopic features and immunohistochemical profile of
      hepatocellular carcinoma. 

PMID- 24040463
TI  - Gangliocytic paraganglioma of the appendix with features suggestive of
      malignancy, a rare case report and review of the literature.
AB  - We report a case of appendicial paraganglioma in a 40 year old female who
      presented with acute appendicitis and underwent laparoscopic appendectomy. To the
      best of our knowledge this is the first reported case of appendicial gangliocytic
      paraganglioma with features suggestive of malignancy in the modern literature.
      Van Eeden S. et al. reported the first case of appendicial paraganglioma in a 47
      year old man who also presented with acute appendicitis. The appendectomy
      specimen showed a distended appendix with thickened wall, and a 1.3 cm mucosal
      based yellow lesion. Microscopically this lesion was centered in the submucosa
      and consisted of three different cell types: (a) epithelioid cells with pale
      eosinophilic finely granular cytoplasm containing bland oval nucleus with
      stippled chromatin, that form solid nests lying in a trabecular pattern and in
      formations reminiscent of 'Zellballen' as seen in paragangliomas (b) second type
      cells have large vesicular nuclei with prominent nucleoli and abundant cytoplasm
      that are scattered singly, (c) third type cells with bland elongated nuclei form
      broad fascicle and envelop the epithelioid and ganglion cells.
      Immunohistochemical analysis showed the epithelioid cell nests immunoreactive for
      synaptophysin and the ganglion-like cells and spindle Schwann cells to be
      immunoreactive for S100 protein, whereas all three cells populations were
      negative for CAM5.2 and Pancytokeratin. We do believe that an accurate diagnosis
      of Gangliocytic paraganglioma (GP) of the appendix was rendered, detailed
      microscopic examination of doubled hematoxylin and eosinophil stained sections as
      well as the immunohistochemical phenotype of the three components have been
      undertaken to confirm the diagnosis of GP. 

PMID- 24040464
TI  - Sporadic hemangioblastoma of the kidney with PAX2 and focal CD10 expression:
      report of a case.
AB  - In this study, we presented an additional case of renal hemangioblastoma, which
      demonstrates PAX2 and focal CD10 expression. Histologically, the tumor consisted
      of sheets of oval or polygonal cells and a prominent vascular network. The tumor
      cells varied in size, and possessed pale or eosinophilic cytoplasm that sometimes
      contained sharply delineated fine vacuoles. The tumor cell nuclei with
      inconspicuous nucleoli showed moderate nuclear atypia and pleomorphism. Focal
      areas of stromal hyalinization and sclerosis were detected. On account of its
      strong or moderate immunoreactivity for the a-inhibin, S100, NSE, and EGFR, the
      diagnosis of renal hemangioblastoma was established. For further evidence of VHL
      deficiency, the tumor was subjected to VHL sequence analysis of all three exons
      and fluorescence in situ hybridization (FISH) detection for chromosome 3p
      deletion. None of the VHL gene mutations and chromosome 3p deletion was detected
      in the tumor. Because of several shared morphological and immunophenotypic
      features, renal hemangioblastoma may be underrecognized and should be included in
      the differential diagnosis of primary renal tumors, in particular clear cell
      renal cell carcinoma. The unexpected positive staining of PAX2 and CD10 in renal
      hemangioblastoma should be particular concerned. Using a combination of
      immunoprofile may be helpful to the differential diagnosis of these renal tumors.

PMID- 24040465
TI  - Lymphoid papillary hyperplasia of the palatine tonsil: a Chinese case report.
AB  - Lymphoid papillary hyperplasia is a rare abnormality of the tonsils with a
      predilection for affecting young Asian girls. Herein, we report a 31-year-old
      Chinese woman presented as right lateral recurrent tonsillar hypertrophy with
      odynophagia and dysphagia over the past 5 years, worsening over a period of for
      half a year. Clinically, this lesion was similar to papillomatosis or lymphoid
      polyposis. However, histopathologic study showed a distinctive form of lymphoid
      hyperplasia with considerable distinct finger-like projections composed of many
      phyllodes which contained remarkable follicular lymphoid hyperplasia. This is the
      only Chinese case of lymphoid papillary hyperplasia of the palatine tonsils that
      has been reported in the most recent English literature so far. The importance of
      recognizing this disorder rests in the fact that in spite of the clinical
      features suggestive of both a benign and a malignant tumor, however, the process
      is a benign tumor-like proliferation, probably non-neoplastic, could easily be
      cured by tonsillectomy. 

PMID- 24040466
TI  - The first reported case of pigmented Bartholin duct cyst.

PMID- 24040468
TI  - Experimental observation of vitro pigs' hearts with bipolar radiofrequency
      ablation.
AB  - Bipolar ablation is an innovative direction of catheter ablation technology. The
      aim of this study was to investigate the damaged area of bipolar radiofrequency
      ablation in vitro pigs' hearts under different conditions and to evaluate the
      effectiveness and safety. The bipolar radiofrequency ablation was performed in
      vitro pigs' hearts with a 4 mm bipolar electrode under different conditions at
      various combinations of the parameters (Distance: from 12 mm to 17 mm; Power: 30
      w or 40 w; Time: from 20 s to 90 s; Temperature: 45 degrees C or 60 degrees C;
      Saline Perfusion: 0 ml/h, 1000 ml/h or 1500 ml/h). We measured the length, width,
      depth, connection rate and blasting rate of the connective ablation lesion and
      then evaluated the effectiveness and safety of connective ablation lesion.
      Numerical analysis showed that there was a positive correlation between the time,
      temperature and the length, depth, connection rate, blasting rate. There was a
      negative correlation between the power, perfusion and the depth, while other
      indexes were positively correlated with the power, perfusion. Distance and length
      were positively correlated, while other indexes were negatively correlated with
      the distance. Regression analysis showed that the infusion was not significantly
      correlated with the depth, connection rate, blasting rate. The temperature was
      not significantly correlated with the length, connection rate. Power and depth's
      correlation was not significant. When the parameter combination was 12 mm, 20 s,
      30 w, 60 degrees C, 1500 ml/h, the effectiveness and safety was optimum, with the
      mean lesion length being 19.89 +/- 3.02 mm, the depth of an average being 3.50 +/
      0.63 mm, the connection rate and the blasting rate being 100% and 13.9%
      respectively. The bipolar ablation in vitro pigs' hearts could form the most
      stable continuous damage. 

PMID- 24040467
TI  - Current Thoughts in Fungal Keratitis: Diagnosis and Treatment.
AB  - Fungal keratitis remains a challenging and often elusive diagnosis in geographic
      regions where it is endemic. Marred by delays in diagnosis, the sequelae of
      corneal fungal infections, though preventable, can be irreversible. Recent
      studies and advances in the arena have broadened the approach and treatment to
      mycotic keratitis. This review will discuss current diagnostic modalities of
      fungal keratitis and will particularly focus on treatment regimens. It will also
      explore future therapeutic models and critique the potential benefit of each.

PMID- 24040469
TI  - Signal transducer and activator of transcription 6 polymorphism and asthma risk:
      a meta-analysis.
AB  - BACKGROUND: The polymorphism in the signal transducer and activators of
      transduction 6 (STAT6) gene has been implicated in susceptibility to asthma and
      aetiology of asthma, but a number of studies have reported inconclusive and
      ambiguous results of the association between polymorphism in STAT6 gene and
      asthma risk in different populations. The aim of this study is to further
      investigate the association between the STAT6 gene polymorphism and asthma
      susceptibility. METHODS: Pubmed, EMBASE, China National Knowledge Infrastructure
      (CNKI) Weipu Database and Wanfang Database were searched to find relevant
      studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to
      assess the strength of association. RESULTS: Included in this meta analysis were
      14 studies involving 2875 cases and 3227 controls for STAT6 2964G/A polymorphism
      and six studies involving 1431 cases and 2027 controls for 2892C/T polymorphism.
      Overall, there was no significant association between 2964G/A polymorphism of
      STAT6 and asthma susceptibility for GA+AA vs. GG (OR = 0.96, 95% CI 0.85-1.07, P
      = 0.39). Except TT vs. CT+CC and TT vs. CC, no significant association was
      observed between 2892C/T polymorphism and asthma risk under other different
      contrast models. However, the result was instable. CONCLUSIONS: This meta
      analysis suggests that the 2964G/A polymorphism of STAT6 gene is not a risk
      factor of asthma. For 2892C/T, it contributes to the aetiology of or
      susceptibility to asthma. More studies are needed to validate this result.

PMID- 24040470
TI  - Plasminogen activator inhibitor-1 4G/5G polymorphism is associated with type 2
      diabetes risk.
AB  - A number of studies were performed to assess the association between plasminogen
      activator inhibitor-1 (PAI-1) 4G/5G polymorphism and susceptibility to type 2
      diabetes (T2DM). However, the results were inconsistent and inconclusive. In the
      present study, the possible association was investigated by a meta-analysis.
      Eligible articles were identified for the period up to June 2013. Pooled odds
      ratios (OR) with 95% confidence intervals (CI) were appropriately derived from
      random-effects models or fixed-effects models. Fourteen case-control studies with
      a total of 2487 cases and 3538 controls were eligible. In recessive model, PAI-1
      4G/5G polymorphism was associated with T2DM risk (OR = 1.23; 95% CI 1.07-1.41; P
      = 0.004). In the subgroup analysis by ethnicity, a significant association was
      found among Asians (OR = 1.27; 95% CI 1.08-1.51; P = 0.005). This meta-analysis
      suggested that PAI-1 4G/5G polymorphism may be associated with T2DM development. 

PMID- 24040471
TI  - Evaluation of diagnostic efficacy of ultrasound scoring system to select thyroid
      nodules requiring fine needle aspiration biopsy.
AB  - INTRODUCTION: The large number of patients that require fine needle aspiration
      biopsy (FNAB) to discriminate malignant from benign thyroid nodules is a
      practical problem especially in iodine deficient area. To obtain an ultrasound
      (US) score and for predicting malignant nodules and reduce the number of
      unnecessary and expensive FNAB. MATERIALS AND METHODS: A total of 280 thyroid
      nodules observed from August 2009 to August 2011 that had underwent FNAB were
      evaluated by US for echogenicity, peripheral halo, microcalcifications and
      intranodular vascularity. RESULTS: showed that nodules with two ultrasonographic
      features (US score = 4) were characterized by a 67.9% sensitivity and a 87%
      specificity for prediction of malignant thyroid nodules. CONCLUSION: According to
      our data, we suggest FNAB for nodules with US score >= 4. The practical use of
      this US score may help reduce unnecessary and expensive FNAB especially in iodine
      deficient areas.

PMID- 24040472
TI  - Clinical study on the treatment of chronic wound with negatively-charged aerosol.
AB  - BACKGROUND: Aerosols are defined as the mixture of liquid or solid
      particles/droplets that are stably suspending in air. When carrying a certain
      amount of negative charge, they will be defined as negatively-charged aerosol.
      This report investigates the effect of negatively-charged aerosol on the healing
      of chronic wound. METHODS: 140 patients with chronic wound were assigned randomly
      into two groups. Normal, routine treatment was applied on chronic wounds of 73
      patients depending on wounds situation (control group). While another 67 similar
      patients received negatively-charged aerosol therapy (2 hours per time, twice a
      day) and were used as experimental group. Wound healing assessment including the
      patients' complication, detection of bacteria in wound secretions, and evaluation
      of wound healing. RESULTS: The results of our study showed that after the
      application of negatively-charged aerosols, and condition and infection rate of
      wounds from experiment group were better and lower than that of control group. In
      comparison with control group, the relative size of wounds from experiment group
      was significantly smaller (P<0.05) at post-treatment day 0, 7, 14, 21 and 28.
      Also, the time required for wound healing in the experimental group was
      significantly shorter (P<0.05) than that in the control group. CONCLUSION:
      Negatively-charged aerosol therapy can accelerate wound healing speed and improve
      the healing of chronic wounds. Thus, we wound recommend the consideration of
      Negatively-charged aerosol therapies in addition to normal wound treatment in
      cases of chronic wound.

PMID- 24040473
TI  - Experimental study of comparing rhEGF with rhbetaFGF on improving the quality of
      wound healing.
AB  - The mechanism and biological effects of comparing recombinant human epidermal
      growth factor (rhEGF) with recombinant human basic fibroblast growth factor
      (rhbetaFGF) were evaluated on the model of incised wounds on ventral side of
      rabbit's ears in order to direct their medication in clinical. Total of 72
      incised wounds on ventral side of 24 New Zealand rabbits' ears were divided
      randomly into two therapeutic groups (rhEGF group with 10 MUg/cm(2) and rhbetaFGF
      group with 100 AU/cm(2)) and a control group (1% silver sulfadiazine cream, SD
      Ag). The observation of wounds, the measurements of healing wound area, the
      calculation of wound closing index, the histopathological examination, the
      electrical microscopic examination, and the expression of examining integrin
      beta1 mRNA of samples of three groups by in situ hybridization technique were
      used to evaluate the results of wound healing. The results showed that the wound
      healing was accelerated in all wounds treated with rhEGF and rhbetaFGF, and the
      quality of healing wounds of two therapeutic groups was better than that of the
      control group. In rhbetaFGF group, new granulation tissue was more than that of
      rhEGF group in earlier period and metaphase of healing wound, however, the
      velocity of re-epithelialization in rhEGF group was faster than that of rhbetaFGF
      group in metaphase and late period. The results indicate that rhEGF and rhbetaFGF
      can improve wound healing, but the detailed mechanisms and the biological effects
      were different. rhbetaFGF may be used to promote the growth of granulation tissue
      in earlier period and metaphase of healing wound, however, rhEGF may be used to
      accelerate the velocity of re-epithelialization in metaphase and late period.
      That rhbetaFGF and rhEGF were utilized in sequence can not only accelerate the
      velocity of healing wound and promote the quality of healing wound but also
      obtain the best ratio of effects versus value. 

PMID- 24040474
TI  - A novel surgical procedure: scaffold-pulmonary autograft transplantation.
AB  - Mitral valve-related operations are easy to perform and show good results, but to
      prevent severe thromboembolism or a high ratio of prosthetic valve destruction by
      tissue, lifetime anticoagulant therapy is essential after the operation. Thus,
      identifying a new type of surgical procedure and prosthetic valve to cure mitral
      valve diseases is necessary. Pulmonary valve autograft transplantation (Ross II)
      with the "top hat" transplantation technique was first reported by Ross DN to
      cure mitral disease. Because the "top hat" procedure has some shortcomings, we
      designed the scaffold-pulmonary autograft transplantation procedure and performed
      animal experiments to confirm the feasibility and effectiveness of the procedure.
      A total of 13 minipigs, weighing 20-25 kg, were employed as experimental animals
      to undergo scaffold-pulmonary autograft valve transplantation in our surgical
      animal lab. The surgical procedure was performed under hypothermic general
      anaesthesia and extracorporeal circulation (or cardiopulmonary bypass, CPB).
      Briefly, the chest cave was opened through the left intercostal, the pulmonary
      valve autograft was harvested during on-pump beating heart, and the pulmonary
      valve autograft was mounted in a self-made pulmonary valve scaffold and
      transferred to the mitral valve annulus without removing the mitral instruments.
      Finally, the outflow tract of the right ventricle was re-established with a pig
      pulmonary homograft. After finishing data collection, all animals were executed 1
      hour after removal from the CPB. For the 13 minipigs that underwent the
      operation, the CPB time was 182.4 +/- 23.4 min. Two of the thirteen cases died of
      bleeding during the operation and of a post-operative pulmonary embolism, and the
      remaining eleven survived for one hour. The pressure of the left atrium did not
      increase significantly (P = 1.00), and the ultrasonic cardiograph (UCG) showed
      good function of the new mitral valves, with mean ejection fraction (EF) values
      of 63.6%. The mitral valve orifice areas were 1.10 +/- 0.13 cm(2) (pre-operation)
      and 1.01 +/- 0.08 cm(2) (post-operation) (P = 0.013). The function and structure
      of the new mitral valves were normal. We preliminarily consider scaffold
      pulmonary autograft valve transplantation to be a new alternative to cure mitral
      valve disease, but advanced chronic animal experiments will be needed to confirm
      the long-term results of the operation. The results showed it could be a new
      alternative to cure mitral valve disease. 

PMID- 24040475
TI  - Exfoliative cytology of oral epithelial cells from patients with type 2 diabetes:
      cytomorphometric analysis.
AB  - This research objective is to identify cytomorphometrical changes using
      exfoliative cytology (EC) and later Papanicolaou (Pap) staining, for oral
      epithelial cells of patients with type 2 diabetes (DM2) (n = 30), while being
      compared to patients without the disease (n = 30). Additionally, we investigated
      an association between cellular changes and salivary flow levels; relationship
      that until now has not been reported. Results show that the cell diameter and the
      nuclear-cytoplasmic ratio was significantly higher compared to those patients
      without the disease (p <= 0.001 Student and Welch test). Decreased salivary flow
      was significantly associated with increased cell diameter and nuclear-cytoplasmic
      ratio (p <= 0.001 ANOVA with Tukey test). Evidence and clinical observations show
      that DM2 and decreased salivary flow are related to detectable cytomorphometrical
      changes in exfoliated cells, which may extend the horizon of this cytological
      technique. 

PMID- 24040476
TI  - PDLIM5 gene polymorphisms and short term antidepressant response in Chinese major
      depressive disorders.
AB  - Several investigations have suggested that PDLIM5 plays a key role in the
      pathophysiology of major depressive disorder (MDD), and that PDLIM5 might be a
      therapeutic target for the action of antidepressant. In this study, we sought to
      investigate whether variations of PDLIM5 gene sequence could predict response to
      antidepressants in MDD patients. We selected 3 SNPs (rs10008257, rs2433320,
      2452600) of PDLIM5 gene, and performed an association analysis of PDLIM5 and the
      efficacy of fluoxetine treatment in 185 Han Chinese MDD patients. The results
      show that the rs2433320 of PDLIM5 gene are associated with fluoxetine therapeutic
      response in MDD patients (X(2) = 8.2960, df = 2, P = 0.0145) after correction
      with the Bonferroni multiple test, the HAMD score of the GG genotype group was
      significantly lower than that of the AA and AG genotype group at 1, 2, 4 and 6
      weeks. The results support the idea that the PDLIM5 gene is likely to be involved
      in the antidepressant response in MDD. 

PMID- 24040477
TI  - The effect of water temperature and voluntary drinking on the post rehydration
      sweating.
AB  - During heat stress and dehydration, thermoregulation is partly suppressed to save
      body fluid and circulation. Drinking induces the recovery of thermoregulatory
      responses including sweating. Our objective is to investigate the effect of water
      temperature and voluntary drinking on the extent of the drinking-induced
      sweating. Six healthy subjects 23.7 +/- 0.6 yr old and 80.7 +/- 5.7 kg wt were
      dehydrated by performing mild exercise (ergometer cycling) in a hot and humid
      chamber (38-40 degrees C, 20-28% relative humidity). After dehydration, subjects
      were allowed to drink water with temperatures of 5, 16, 26, 58 degrees C on four
      separate days. The sweating rate was measured on the forehead area before and
      after drinking. Also, blood samples were collected during the experiments and
      plasma osmolality was measured. Sweating increased markedly just a few minutes
      after the onset of drinking. The rate of this response was lower in ingested
      water temperature of 5 degrees C (0.43 +/- 0.03 g, p = 0.000). Different intake
      occurred with different water temperatures (respectively 4.2, 6.4, 3.1, 1.8
      ml/kg). Water at 16 degrees C induced higher intake (6.4 ml/kg) together with
      lower sweating (0.54 +/- 0.03 g), which can result in optimum level of hydration.
      Conclusion- When dehydrated subjects drink water with different temperatures,
      there are different sweating responses together with different voluntary intakes.
      According to our results, consuming 16 degrees C water, cool tap water, could be
      suggested in dehydration. 

PMID- 24040478
TI  - Value of the frontal planar QRS-T angle on cardiac dysfunction in patients with
      old myocardial infarction.
AB  - OBJECTIVES: To explore a method of surface electrocardiogram for assessing
      cardiac dysfunction in patients with old myocardial infarction. METHODS: 1000
      patients with old myocardial infarction in Anzhen hospital were analyzed
      retrospectively. The planar QRS-T angle was calculated automatically according to
      QRS-wave and T-wave vectors by the electrocardiogram machine. RESULTS: Among
      these 1000 patients, 822 (82.2%) were male and 178 (17.8%) were female, the mean
      age was 59.3+/-10.5 years (34~89 years). The average planar QRS-T angle was
      88.5+/-50.6 degrees . The planar QRS-T angle and LVEF was negative correlation
      (r=-0.406, p<0.01), the lower the LVEF, the better the relationship with planar
      QRS-T angle. QRS-T angle>90 degrees  had optimal sensitivity and specificity
      (76%, 74%) in diagnosis of cardiac dysfunction. CONCLUSION: The planar QRS-T
      angle and LVEF of patients with old myocardial infarction is negative
      correlation, the larger the planar QRS-T angle, the lower the LVEF. The planar
      QRS-T angle may be an easier and more feasible index for assessing cardiac
      dysfunction in patients with old myocardial infarction.

PMID- 24040479
TI  - 116 cases of neonatal early-onset or late-onset sepsis: A single center
      retrospective analysis on pathogenic bacteria species distribution and
      antimicrobial susceptibility.
AB  - PURPOSE: The aim of this study was to explore the risk factors, clinical
      symptoms, hematological parameters, causative pathogen and antibiotic
      susceptibility of neonatal sepsis in a Chinese NICU. METHODS: A retrospective
      survey was conducted on 116 cases of neonatal sepsis in NICU at the Maternal and
      Child Care Hospital in Shenzhen, China from January 2009 to December 2012.
      Patients were divided into early-onset sepsis (EOS) and late-onset sepsis groups
      according to their positive blood culture occurrence time (in the first 7 days of
      life or later). RESULTS: 116 cases of neonatal sepsis were divided into early
      onset sepsis (EOS) group and late-onset sepsis (LOS) group. There was significant
      difference for risk factors like peripherally insertion central catheter (PICC)
      between two groups. The clinical symptoms or laboratory results such as chilly
      periphery, fever, jaundice, platelet and hemoglobin also had between-group
      differences. The most common responsible pathogenic bacteria species present in
      EOS group was Coagulase-negative Staphylococcus (CoNS). Among those CoNS
      Staphylococcus epidermidis provided 24.24%, and Staphylococcus haemolyticus
      contributed 13.63%. Both were sensitive to vancomycin, teicoplanin and linezolid.
      The most common responsible pathogenic bacteria species in LOS group was
      Staphylococcus epidermidis (16%). Antimicrobial susceptibility in EOS group is
      higher than in LOS group. CONCLUSION: PICC is a bigger risk factor for neonatal
      late-onset sepsis. Staphylococcus epidermidis was the leading pathogen present in
      neonatal sepsis in a tertiary maternal & child care hospital in southern China.
      Vancomycin, teicoplanin and linezolid may be the best choice to management of
      neonatal sepsis.

PMID- 24040480
TI  - MMP-2 and DcR3 expression in esophageal cancer tissue and correlation with
      patient survival.
AB  - OBJECTIVE: This study aims to explore the expression of decoy receptor 3 (DcR3)
      and the matrix metalloproteinase-2 (MMP-2) in esophageal carcinoma and their
      relationship with patient survival. METHODS: The EnVision(TM)
      immunohistochemistry method was used to examine DcR3 and MMP-2 expression in 150
      surgical biopsies of esophageal carcinoma. Expression level was compared with
      clinical indices and with patient survival. RESULTS: In cancer tissues, the
      positive expression rate of DcR3 and MMP-2 was 54.00% and 54.67% respectively;
      this was higher than levels in adjacent normal tissue. DcR3 and MMP-2 were
      positively correlated with carcinoma size, lymphatic metastasis, invasion degree,
      clinical stage and 3-year survival. DcR3 and MMP-2 were not correlated with
      gender, age and tumor degree of differentiation. DcR3 and MMP-2 were positively
      correlated between in the two groups (r = 0.37, P < 0.01). Kaplan-Meier survival
      curve showed that higher rates of DcR3 and MMP-2 expression correlated with lower
      survival. CONCLUSIONS: Determining DcR3 and MMP-2 expression may be useful for
      the diagnosis, treatment and prognosis of patients with esophageal carcinoma.

PMID- 24040481
TI  - Circulating levels of erythropoietin and its relation to arterial stiffness in
      patients with hypertension.
AB  - BACKGROUND: Emerging experimental and clinical data indicates that erythropoietin
      (EPO) have significant roles in the cardiovascular system. But the relationship
      between endogenous EPO levels and arterial stiffness remains unknown. We
      investigated the EPO levels in relation to arterial stiffness parameters in
      patients with never treated newly diagnosed hypertension (HT). METHODS: We
      studied 42 (47.8 +/- 10 years) never treated HT patients and age and gender
      matched 40 (47 +/- 8.6 years) normotensive individuals. Serum EPO levels were
      determined in all subjects using the chemiluminescence immunoassay kit. We
      evaluated heart rate-corrected augmentation index (AIx@75), a marker of wave
      reflections and aortic pulse wave velocity (PWV) as indices of elastic-type
      aortic stiffness using applanation tonometry (Sphygmocor). RESULTS: The levels of
      EPO were not significantly different in hypertensive patients and the controls
      (10.6 +/- 5 vs. 11.6 +/- 9, mIU/mL, p = 0.5). Aortic PWV (10.3 +/- 2.3 vs. 8.7 +/
      1.6 m/s, p = 0.0001) and AIx@75 (22.7 +/- 10 vs. 15 +/- 11, %, p = 0.002) were
      significantly higher in hypertensive patients than the controls. EPO levels were
      not correlated with brachial and central pressures. Also EPO level was not
      significantly correlated with AIx@75 (r = -0.15, p = 0.17) and aortic PWV (r = 
      0.16, p = 0.13). CONCLUSION: Results from this study indicate that endogenous EPO
      levels may not be a factor in development of increased arterial stiffness.

PMID- 24040482
TI  - The effect of pre-competition training on biochemical indices and immune function
      of volleyball players.
AB  - OBJECTIVE: Pre-competition sports training can have varying effects on an
      athlete's immune function, including causing reduced resistance. The aim of this
      study was to explore effects of pre-competition training on some biochemical
      indices and immunologic functions in top-level volleyball athletes to determine
      whether training should be modified for optimal health. METHODS: Biochemical
      indices (Hb, BUN, CK, LDH) and immunologic function (IgA, IgG, IgM, CD3(+),
      CD4(+), CD8(+)) were detected by semiautomatic biochemistry analyzer, light
      scattering photometer, or flow cytometry in sera from 24 top-level volleyball
      athletes and compared before and after pre-competition training. RESULTS: After
      training, the levels of Hb, IgA, IgG, IgM, and CD4(+) and the CD4(+)/CD8(+) ratio
      decreased significantly, while BUN, CK, LDH, and CD8(+) increased significantly
      (P < 0.05). Further, the decrease in Hb levels in female athletes was more
      significant than that in male athletes (P < 0.05). CONCLUSIONS: These results
      indicate that pre-competition training affects biochemical indices and
      immunologic function in this group of athletes. Additionally, more dramatic
      changes in Hb in female athletes may indicate a need for adapted training loads
      and rest periods for females.

PMID- 24040483
TI  - Combined general and regional anesthesia and effects on immune function in
      patients with benign ovarian tumors treated by laparoscopic therapy.
AB  - OBJECTIVE: Anesthesia has been shown to suppress immune function, which can
      negatively affect the treatment of patients with various tumors. Here, we
      assessed two different anesthesia methods, general versus combined
      regional/general, in treatment of benign ovarian tumor by laparoscopic therapy.
      METHODS: Out of 160 patients with benign ovarian tumors treated by laparoscopic
      therapy, 80 received general anesthesia combined with thoracic epidural
      anesthesia during surgery, and 80 received general anesthesia only. Venous blood
      samples were obtained at the following time points: before induction of
      anesthesia (T0), 2 hours after anesthesia, during operation, 3 days (d) after
      operation, 5 d after operation, and 7 d after operation. Percentages of CD3(+),
      CD4(+), and CD4(+)/CD8(+) T lymphocytes were determined at these time points by
      flow cytometry to assess immune function. RESULTS: For both groups, percentages
      of CD3(+), CD4(+), and CD4(+)/CD8(+) T cells decreased significantly from T0 to 2
      hr after anesthesia (P < 0.05). These percentages decreased again during surgery.
      However, T cell percentages in patients receiving combined anesthesia returned to
      normal levels 5 d after surgery, and those receiving only intravenous anesthesia
      returned to normal by 7 d after surgery. There were no significant differences in
      CD3(+), CD4(+), or CD4(+)/CD8(+) T cell percentages between the two anesthesia
      groups at T0 and 7 d. However, significant differences in these percentages were
      observed between the two groups at all other time points. Interestingly, the
      decrease observed within the combined group were less dramatic than those
      observed within the intravenous-only group (P < 0.05). CONCLUSIONS: These
      findings indicate that, while any anesthesia may suppress immune function of
      patients treated by laparoscopic therapy, the effect of general anesthesia
      combined with thoracic epidural anesthesia on immune function was less than that
      produced by general anesthesia alone.

PMID- 24040484
TI  - Bilateral sudden hearing loss following habitual abortion: a case report and
      review of literature.
AB  - Sudden sensorineural hearing loss (SSNHL) is usually unilateral and can be
      associated with tinnitus and vertigo. The most common causes of this disease are
      known to be the vascular and viral agents, but immune disorders are involved in
      the development of sudden deafness. The antiphospholipid syndrome (APS) is an
      acquired autoimmune system disorder, which is defined as the presence of
      antiphospholipid antibodies (APA) in the patient's blood, then cause venous
      and/or arterial thrombosis in various organs of the body, for example, thrombosis
      can occur in the placenta and/or the inner ear. As a result, it can cause
      abortion and/or sudden deafness. Bilateral SSNHL following habitual abortion is a
      rare clinical event. Here, we report a case of 32-year-old woman who presented
      with bilateral sudden hearing loss following recurrent pregnancy loss (RPL) as
      the first manifestation of primary antiphospholipid syndrome. Combine the
      literature, the diagnosis, clinical implication and treatment are discussed. 

PMID- 24040485
TI  - Impact of brand-name drug worship and expectation psychology on antidepressant
      efficacy.
AB  - The choice of the generic drug is reasonable if there is evidence for its
      therapeutic equivalence with the brand-name drug. However, the reduced
      effectiveness of switching from brand-name drug to generic drug is not rare. The
      impact of brand-name worship and expectation psychology on drug efficacy is
      noteworthy to report. A 45-year-old woman suffered from depression mood disorder.
      She experienced profound improvement in her depressive symptoms after a switch
      from domestic generic venlafaxine to imported brand-name counterpart. The
      interview showed that the woman has a strong brand-name drug worship and
      expectation psychology, which is representative, typical and popular in China
      especially in vast rural areas. Medication education does not work too much. The
      brand-name drug worship and expectation psychology might improve drug efficacy
      when patient is switched from generic drug to branded medication. 

PMID- 24040486
TI  - Identification of Potent and Selective Diphenylpropanamide RORgamma Inhibitors.
AB  - Retinoic acid-related orphan receptor RORgammat plays a pivotal role in the
      differentiation of TH17 cells. Antagonizing RORgammat transcriptional activity is
      a potential means to treat TH17-related autoimmune diseases. Herein, we describe
      the identification of a series of diphenylpropanamides as novel and selective
      RORgamma antagonists. Diphenylpropanamide 4n inhibited transcriptional activity
      of RORgammat, but not RORalpha, in cells. In addition, it suppressed human TH17
      cell differentiation at sub-micromolar concentrations.

PMID- 24040487
TI  - Pharmacological activity of retinoic acid receptor alpha-selective antagonists in
      vitro and in vivo.
AB  - Oral administration of a retinoic acid receptor (RAR) pan-antagonist reversibly
      inhibits spermatogenesis. Given the importance of RARalpha in regulating
      spermatogenesis, we identified two RARalpha-selective antagonists by
      transactivation and transactivation competition assays and asked whether they
      effectively inhibit spermatogenesis. Although these two antagonists were potent
      in vitro, they displayed poor in vivo activity in mice when administered orally.
      Testicular weights were normal and morphological analysis revealed normal
      spermatid alignment and sperm release. In vitro drug property analyses were
      performed with one of these antagonists and compared with the pan-antagonist. We
      showed that the discrepancies may be explained by several factors, including high
      plasma protein binding, faster hepatic metabolism relative to the pan-antagonist,
      and only moderate permeability. The conclusion of poor oral bioavailability was
      supported by more pronounced defects in mice when the antagonist was administered
      intravenously versus intraperitoneally. These results are crucial for designing
      new RARalpha-selective antagonists for pharmaceutical application.

PMID- 24040488
TI  - An analysis of clinical activity, admission rates, length of hospital stay, and
      economic impact after a temporary loss of 50% of the non-operative podiatrists
      from a tertiary specialist foot clinic in the United Kingdom.
AB  - INTRODUCTION: Podiatrists form an integral part of the multidisciplinary foot
      team in the treatment of diabetic foot-related complications. A set of unforeseen
      circumstances within our specialist diabetes foot service in the United Kingdom
      caused a loss of 50% of our non-operative podiatry team for almost 7 months
      during 2010. Some of this time was filled by non-specialist community non
      operative podiatrists. METHODS: We assessed the economic impact of this loss by
      examining data for the 5 years prior to this 7-month interruption, and for the 2
      years after 'normal service' was resumed. RESULTS: Our data show that the loss of
      the non-operative podiatrists led to a significant rise in the numbers of
      admissions into hospital, and hospital length of stay also increased. At our
      institution a single bed day cost is L275. During the time that the numbers of
      specialist non-operative podiatry staff were depleted, and for up to 6 months
      after they returned to normal activities, the extra costs increased by just less
      than L90,000. The number of people admitted directly from specialist vascular and
      orthopaedic clinics is likely to have increased due to the lack of capacity to
      manage them in the diabetic foot clinic. Our data were unable to assess these
      individuals and did not look at the costs saved from avoiding surgery. Thus the
      actual costs incurred are likely to be higher. CONCLUSIONS: Our data suggest that
      specialist non-operative podiatrists involved in the treatment of the diabetic
      foot may prevent unwarranted hospital admission and increased hospitalisation
      rates by providing skilled assessment and care in the outpatient clinical
      settings.

PMID- 24040489
TI  - Infant BMI trajectories are associated with young adult body composition.
AB  - The dynamic aspect of early life growth is not fully captured by typical
      analyses, which focus on one specific time period. To better understand how
      infant and young child growth relate to the development of adult body
      composition, the authors characterized body mass index (BMI) trajectories using
      latent class growth analysis (LCGA) and evaluated their association with adult
      body composition. Data are from the Cebu Longitudinal Health and Nutrition
      Survey, which followed a birth cohort to age 22 years (n = 1749). In both males
      and females, LCGA identified seven subgroups of respondents with similar BMI
      trajectories from 0 to 24 months (assessed with bimonthly anthropometrics).
      Trajectory groups were compared with conventional approaches: (1) accelerated
      growth between two time points (0-4 months), (2) continuous BMI gain between two
      points (0-4 months and 0-24 months) and (3) BMI measured at one time point (24
      months) as predictors of young adult body composition measures. The seven
      trajectory groups were distinguished by age-specific differences in tempo and
      timing of BMI gain in infancy. Infant BMI trajectories were better than
      accelerated BMI gain between 0 and 4 months at predicting young adult body
      composition. After controlling for BMI at age 2 years, infant BMI trajectories
      still explained variation in adult body composition. Using unique longitudinal
      data and methods, we find that distinct infant BMI trajectories have long-term
      implications for the development of body composition. 

PMID- 24040491
TI  - Rapid diagnosis of combined multifocal gastrointestinal stromal tumours and
      coeliac disease in a patient with type 1 neurofibromatosis.

PMID- 24040490
TI  - Cardiometabolic interventions - focus on transcriptional regulators.
AB  - Cardiovascular disease (CVD) remains the largest healthcare burden in the Western
      world; and the increasing prevalence of type II diabetes mellitus, at least
      partially driven by a trend in lifestyle changes associated with global economic
      development, is likely to fuel this CVD burden worldwide. Over the past two
      decades, there has been an increased awareness of the convergence of risk factors
      contributing to both cardiovascular disease and diabetes leading to the concept
      of the metabolic syndrome, and the realisation of the opportunity to intervene at
      this intersection to simultaneously target CVD and metabolic dysfunction. This
      brings together the fields of cardiovascular medicine, diabetology, and
      increasingly clinical immunology for a unified and concerted effort to reduce
      risk for both conditions simultaneously. The discovery of the targeted pathways
      of drugs already in clinical use such as fibrates and thiazolidinediones (TZD)
      has led to accelerated basic and clinical research into selective and dual PPAR
      alpha and PPAR-gamma agonists, which can theoretically target glucose, lipid and
      lipoprotein metabolism, as well as potentially exerting inhibitoryeffects in
      vascular inflammation, all of which might be predicted to reduce atherosclerosis.
      In this article, we will discuss the basic science as well as recent clinical
      development in the pursuit of optimal cardiometabolic intervention along with
      insight into strategies for future drug development.

PMID- 24040492
TI  - Evidence and ideology as a rationale for light-therapy in Russia: from the Soviet
      Union to the present day.
AB  - Light therapy is still used to treat a number of common diseases in Russia. The
      practice is firmly anchored in history: Soviet clinical practice was divorced
      from the emerging field of evidence-based medicine. Medical researchers were cut
      off from international medical research and scientific literature, with much
      Soviet scientific activity based on a particular socialist ideology. In this
      study, the use of light therapy serves as a case study to explore tensions
      between international evidence-based medicine and practices developed in
      isolation under the Soviet Union, the legacy of which is to the detriment of many
      patients today. We used four different search methods to uncover scientific and
      grey literature, both historical and contemporary. We assessed the changing
      frequency of publications over time and contrasted the volume of literature on
      light therapy with more orthodox treatments such as statins and painkillers. Our
      search found an increasing number and comparatively large body of scientific
      publications on light therapy in the Russian language, and many publications
      emanating from prestigious Russian institutions. Combined with our analysis of
      the historical literature and our appraisal of 22 full text articles, this leads
      us to suggest that light therapy entered mainstream Soviet medical practice
      before the Stalinist period and still occupies an important position in
      contemporary Russian clinical practice. We propose that this outdated treatment
      survives in Russia in part due to the political, economic and social forces that
      helped to popularize it during Soviet times, and by the seeming justification
      offered by poorly executed studies. 

PMID- 24040493
TI  - How do online patient support communities affect the experience of inflammatory
      bowel disease? An online survey.
AB  - OBJECTIVE: To explore how participation in an online support community may impact
      upon the experience of inflammatory bowel disease (IBD). DESIGN: An online
      survey. SETTING: Study participants recruited through 35 IBD online communities.
      PARTICIPANTS: A total of 249 males and females aged 16-69 years, living with
      either Crohn's disease (65.9%) or ulcerative colitis (26.1%) or awaiting formal
      diagnosis (8%). RESULTS: Patients reported being members for an average of two
      years, with the majority accessing the community on a daily (46.9%) or weekly
      (40%) basis. Spending on average four hours per week online, approximately two
      thirds of members posted between one and five messages per week. Members joined
      to find others in a similar situation and to obtain and share information and
      emotional support. Through participation members accessed a wealth of knowledge
      about all aspects of living with IBD and this was helpful in terms of accepting
      their illness and learning to manage it. The community also helped members see
      their illness more positively as well as contributing to an improvement in
      subjective wellbeing. However, some negatives aspects were noted. CONCLUSIONS:
      Online support communities may provide a useful shared space through which IBD
      patients may seek and provide both informational and emotional support. Many of
      these benefits may not be available through traditional healthcare. Whilst online
      support communities may be beneficial for those who choose to participate in
      them, they are not without limitations. Health professionals should be aware of
      the potential benefits and limitations of online communities.

PMID- 24040494
TI  - Hypertriglyceridemic pancreatitis in pregnancy: case reports and review of the
      literature.

PMID- 24040495
TI  - What drives the 'August effect'? A observational study of the effect of junior
      doctor changeover on out of hours work.
AB  - OBJECTIVE: To investigate whether measurements of junior doctor on-call workload
      and performance can clarify the mechanisms underlying the increase in morbidity
      and mortality seen after junior doctor changeover: the 'August effect'. DESIGN:
      Quantitative retrospective observational study of routinely collected data on
      junior doctor workload. SETTING: Two large teaching hospitals in England.
      PARTICIPANTS: Task level data from a wireless out of hours system (n = 29,885
      requests) used by medical staff, nurses, and allied health professionals. MAIN
      OUTCOME MEASURES: Number and type of tasks requested by nurses, time to
      completion of tasks by junior doctors. RESULTS: There was no overall change in
      the number of tasks requested by nurses out of hours around the August changeover
      (median requests per hour 15 before and 14 after, p = 0.46). However, the number
      of tasks classified as urgent was greater (p = 0.016) equating to five more
      urgent tasks per day. After changeover, doctors took less time to complete tasks
      overall due to a reduction in time taken for routine tasks (median 74 vs. 66 min;
      p = 3.9 * 10(-9)). CONCLUSION: This study suggests that the 'August effect' is
      not due to new junior doctors completing tasks more slowly or having a greater
      workload. Further studies are required to investigate the causes of the increased
      number of urgent tasks seen, but likely factors are errors, omissions, and poor
      prioritization. Thus, improved training and quality control has the potential to
      address this increased duration of unresolved patient risk. The study also
      highlights the potential of newer technologies to facilitate quantitative study
      of clinical activity.

PMID- 24040496
TI  - Neglected patellar tendon rupture. Reconstruction using semitendinosus-gracilis
      tendon grafts and FiberWire augmentation.

PMID- 24040497
TI  - Managing patients for zoonotic disease in hospitals.
AB  - Zoonoses involve infections and infestations transmissible from animals to
      humans. Zoonoses are a major global threat. Exposure to zoonotic pathogens exists
      in various settings including encroachment on nature; foreign travel; pet
      keeping; bushmeat consumption; attendance at zoological parks, petting zoos,
      school 'animal contact experiences', wildlife markets, circuses, and domesticated
      and exotic animal farms. Under-ascertainment is believed to be common and the
      frequency of some zoonotic disease appears to be increasing. Zoonoses include
      direct, indirect and aerosolized transmission. Improved awareness of zoonoses in
      the hospital environment may be important to the growing need for prevention and
      control. We reviewed relevant literature for the years 2000 to present and
      identified a significant need for the promotion of awareness and management of
      zoonoses in the hospital environment. This article provides a new decision-tree,
      as well as staff and patient guidance on the prevention and control of zoonoses
      associated with hospitals. 

PMID- 24040498
TI  - Inappropriate use of proton pump inhibitors among medical inpatients: a
      questionnaire-based observational study.
AB  - OBJECTIVES: To evaluate the appropriateness of proton pump inhibitor (PPI)
      prescribing by conducting an audit of medical inpatients against recommended
      guidelines. DESIGN: Questionnaire-based study. All medical wards were audited and
      different information was documented by patients' medical records review (both
      hospital visit notes and general practitioner's letters) and short interview,
      where we asked them to name the clinical reason for using PPI. SETTING: This
      study was carried out in the setting of a regional hospital (537-bed, secondary
      care referral centre) in Ireland. PARTICIPANTS: The study participants were all
      consecutive medical patients admitted to the medical wards at Waterford Regional
      Hospital, Waterford. MAIN OUTCOME MEASURES: The appropriateness of PPI usage in
      our regional hospital by assessing the level of its prescribing against published
      guidelines (NICE, 2000). RESULTS: During the audit period, 205 consecutive
      medical inpatients were assessed. Seventy-nine percent (162 out of 205) of the
      studied patients were found to be using PPI. For 45% (n = 73) of patients, there
      was no documentation of valid indication for being on PPI. Overall, 64% of
      patients were prescribed PPI by hospital doctors, either during their current or
      previous admissions. We noted that 31% (n = 51) of patients were taking PPI for
      >=2 years and another 25% of patients were using PPI for about one year. Only 12%
      (n = 20) of patients had undergone endoscopy procedures. CONCLUSION:
      Inappropriate use of PPI remains common in hospital practice. The risks of using
      long-term PPI must be weighed against the benefits.

PMID- 24040499
TI  - Antibacterial effect of incorporating silver ions in electrochemically deposited
      hydroxyapatite coating: An experimental study.

PMID- 24040500
TI  - Avastin and Lucentis: what do patients know? A prospective questionnaire survey.
AB  - OBJECTIVES: To assess patients' knowledge of their drug therapy for neovascular
      macular degeneration and to identify which aspects of the drug they considered
      most important if given the option of switching to an alternative drug. DESIGN:
      Prospective questionnaire survey. SETTING: Wolverhampton, England. PARTICIPANTS:
      A total of 126 patients attending our hospital service for intravitreal
      ranibizumab therapy for neovascular macular degeneration. MAIN OUTCOME MEASURES:
      Using a questionnaire, patients were asked questions pertaining to aspects of
      drug therapy in neovascular macular degeneration. Fields covered included drug
      names, knowledge of alternative drugs, cost of drugs and their views on switching
      to another drug. RESULTS: Eighty (63.5%) had heard of Lucentis (ranibizumab) and
      31 (24.6%) were aware of Avastin (bevacizumab). Of the latter 31 patients, 20 did
      not have a preference between Avastin and Lucentis. These patients felt that the
      factors they would consider important for them to consider switching were
      effectiveness (10, 50%), specialist recommendation (8, 40%), safety (2, 10%) and
      cost (0). CONCLUSIONS: Introducing a cheaper, off-label alternative in the
      therapy of macular degeneration in the presence of a licensed option has been
      extensively debated. Many patients have no knowledge of this controversial issue
      but it is likely that efficacy and recommendation by clinicians are more
      important than cost to patients who may consider switching to the off-label
      Avastin.

PMID- 24040501
TI  - An important diagnosis to consider in recurrent meningitis.

PMID- 24040502
TI  - Sustained bilateral middle ear effusions post orthognathic surgery successfully
      treated with grommet insertion.

PMID- 24040503
TI  - Fatal pulmonary embolism update: 10 years of autopsy experience at an academic
      medical center.
AB  - OBJECTIVE: To investigate the rate of death caused by pulmonary embolism (PE) and
      the antemortem performance in diagnosis and treatment of PE. DESIGN: A systematic
      search of cases involving fatal PE via PowerPath(r) (Sunquest) followed by chart
      review. SETTING: An academic medical centre located in San Diego, United States
      of America. PARTICIPANTS: Postmortem cases with pathological findings of PE. MAIN
      OUTCOME MEASURES: After data collection and collation, the data were subject to
      analysis. RESULTS: From 2002 to 2012, PE was identified as the mechanism of death
      in 108 of 982 cases (11%, 95% CI 9.01-12.99%) at an institution with an average
      autopsy rate of 30% +/- 0.07%. Excluding cases where care was withheld (by
      advance directive) or unavailable, 29 of 108 were eligible for antemortem
      treatment for PE. In 31% (nine of 29) of these cases the diagnosis of PE was
      considered antemortem. Only three of 29 were given thrombolytics despite only one
      case being contraindicated. CONCLUSION: The rate of PE-related death is
      consistent with most other autopsy series and major epidemiologic studies despite
      advances in system wide deep venous thrombosis prophylaxis. The results validate
      previous studies that this diagnosis is often missed but probably improving
      compared to historical standards. Even when the diagnosis is considered, however,
      thrombolytics are not routinely given, even without contraindications. The cause
      of this failure to treat may require further study with comparison to patients
      that were treated to determine the utilization of this treatment. It also
      underscores the continued difficulty in the diagnosis of this disease.

PMID- 24040504
TI  - Prevalence of cholecystitis in gallbladder histology following clinical
      pancreatitis: cohort study.

PMID- 24040505
TI  - An exploration of the relationship between placebo and homeopathy and the
      implications for clinical trial design.
AB  - Placebo appears to be a real neurobiological phenomenon that has evolved through
      the selection pressure to be able to heal ourselves. The complex language and
      social structures of humans means that we can attribute meaning to therapeutic
      encounters with culturally sanctioned authority figures and we can use our
      attachment to such figures to generate hope for recovery. Different mechanisms
      may be involved in the neurobiological aspect of placebo including anxiety,
      learning, conditioning as well as individual genetic variation. Examination of
      the published work shows that while some trials do seem to indicate a specific
      mode of action for homeopathic remedies other trials do not and this is an issue
      that needs to be addressed at the trial design stage. A clinical trial that
      includes both a placebo group and a non-participating control arm is the most
      powerful design for separating the non-specific and polymorphic placebo effect
      from the specific effects of trial medication. The control variables in a trial
      of homeopathic medication should also include the process of consultation as this
      may assume a meaning for the individual that can also be associated with a
      placebo effect. 

PMID- 24040506
TI  - Next-generation therapeutic solutions for age-related macular degeneration.
AB  - Age-related macular degeneration (AMD) is the primary cause of irreversible
      blindness among the elderly in the western world. To date, no cure is available
      and the current anti-VEGF therapy has only shown limited efficacy in improving
      visual acuity in neovascular AMD. The etiology of AMD remains elusive but
      research over the past decade has uncovered characteristic features of the
      disease. These features include: oxidative stress and retinal pigment epithelial
      cell cytotoxicity; loss of macromolecular permeability and hydraulic conductivity
      in Bruch's membrane; inflammation; choroidal neovascularization and vascular
      leakage; and loss of neuroprotection. Recent breakthroughs in understanding the
      pathogenesis of AMD have spawned an array of novel therapeutic agents designed to
      address these hallmarks. Here we review the features of AMD and highlight the
      most promising therapeutic and diagnostic approaches based on the patents
      published from 2008 to 2011.

PMID- 24040507
TI  - Relationship between premature ventricular complexes and depressive symptoms in
      non-ST-elevation acute coronary syndrome.
AB  - AIMS: Depression is a recognized risk marker for mortality among acute coronary
      syndrome (ACS) patients. We hypothesized that ventricular arrhythmia detected by
      inpatient telemetry monitoring is more frequent among ACS patients with elevated
      depressive symptoms compared to those without depressive symptoms. METHODS AND
      RESULTS: We analysed data from patients enrolled in a prospective observational
      study of depression in ACS. Telemetry recordings during the index admission
      (average recording 21.3+/-3.0 hours) were analysed for frequent premature
      ventricular complexes (PVCs), defined as >=10 per hour. The self-report Beck
      Depression Inventory (BDI) was used to assess depressive symptoms. Among 200 ACS
      patients, frequent PVCs were observed in 29% of patients with moderate depressive
      symptoms (BDI >=10), 27% of those with mild symptoms (BDI 5-9), and only 11% of
      those with no/minimal symptoms (p=0.02). Log-transformed PVCs per hour were
      associated with depressive symptom category (p=0.008). In a multivariable
      logistic regression model that included age, gender, left ventricular ejection
      fraction, cardiovascular risk score, heart rate, and QT interval, mild symptoms
      (OR 3.02, 95% 0.97-9.43, p=0.058) and moderate-severe symptoms (OR 3.94, 95% CI
      1.27-12.22, p=0.018) were associated with frequent PVCs. CONCLUSIONS: In this
      sample of ACS patients, depressive symptoms were independently associated with
      frequent PVCs during inpatient telemetry monitoring.

PMID- 24040508
TI  - Tissue absence initiates regeneration through follistatin-mediated inhibition of
      activin signaling.
AB  - Regeneration is widespread, but mechanisms that activate regeneration remain
      mysterious. Planarians are capable of whole-body regeneration and mount distinct
      molecular responses to wounds that result in tissue absence and those that do
      not. A major question is how these distinct responses are activated. We describe
      a follistatin homolog (Smed-follistatin) required for planarian regeneration.
      Smed-follistatin inhibition blocks responses to tissue absence but does not
      prevent normal tissue turnover. Two activin homologs (Smed-activin-1 and Smed
      activin-2) are required for the Smed-follistatin phenotype. Finally, Smed
      follistatin is wound-induced and expressed at higher levels following injuries
      that cause tissue absence. These data suggest that Smed-follistatin inhibits Smed
      Activin proteins to trigger regeneration specifically following injuries
      involving tissue absence and identify a mechanism critical for regeneration
      initiation, a process important across the animal kingdom.
      DOI:http://dx.doi.org/10.7554/eLife.00247.001. 

PMID- 24040510
TI  - Learning about loss.
AB  - Researchers have identified two genes-follistatin and activin-as having an
      important role in the ability of certain flatworms to identify wounds that
      require the production of new tissue. 

PMID- 24040509
TI  - Imaging-based chemical screening reveals activity-dependent neural
      differentiation of pluripotent stem cells.
AB  - Mammalian pluripotent stem cells (PSCs) represent an important venue for
      understanding basic principles regulating tissue-specific differentiation and
      discovering new tools that may facilitate clinical applications. Mechanisms that
      direct neural differentiation of PSCs involve growth factor signaling and
      transcription regulation. However, it is unknown whether and how electrical
      activity influences this process. Here we report a high throughput imaging-based
      screen, which uncovers that selamectin, an anti-helminthic therapeutic compound
      with reported activity on invertebrate glutamate-gated chloride channels,
      promotes neural differentiation of PSCs. We show that selamectin's pro-neurogenic
      activity is mediated by gamma2-containing GABAA receptors in subsets of neural
      rosette progenitors, accompanied by increased proneural and lineage-specific
      transcription factor expression and cell cycle exit. In vivo, selamectin promotes
      neurogenesis in developing zebrafish. Our results establish a chemical screening
      platform that reveals activity-dependent neural differentiation from PSCs.
      Compounds identified in this and future screening might prove therapeutically
      beneficial for treating neurodevelopmental or neurodegenerative disorders.
      DOI:http://dx.doi.org/10.7554/eLife.00508.001. 

PMID- 24040512
TI  - Collaboration gets the most out of software.
AB  - By centralizing many of the tasks associated with the upkeep of scientific
      software, SBGrid allows researchers to spend more of their time on research. 

PMID- 24040511
TI  - An essential role for maternal control of Nodal signaling.
AB  - Growth factor signaling is essential for pattern formation, growth,
      differentiation, and maintenance of stem cell pluripotency. Nodal-related
      signaling factors are required for axis formation and germ layer specification
      from sea urchins to mammals. Maternal transcripts of the zebrafish Nodal factor,
      Squint (Sqt), are localized to future embryonic dorsal. The mechanisms by which
      maternal sqt/nodal RNA is localized and regulated have been unclear. Here, we
      show that maternal control of Nodal signaling via the conserved Y box-binding
      protein 1 (Ybx1) is essential. We identified Ybx1 via a proteomic screen. Ybx1
      recognizes the 3' untranslated region (UTR) of sqt RNA and prevents premature
      translation and Sqt/Nodal signaling. Maternal-effect mutations in zebrafish ybx1
      lead to deregulated Nodal signaling, gastrulation failure, and embryonic
      lethality. Implanted Nodal-coated beads phenocopy ybx1 mutant defects. Thus, Ybx1
      prevents ectopic Nodal activity, revealing a new paradigm in the regulation of
      Nodal signaling, which is likely to be conserved.
      DOI:http://dx.doi.org/10.7554/eLife.00683.001. 

PMID- 24040513
TI  - Spectral Phasor approach for fingerprinting of photo-activatable fluorescent
      proteins Dronpa, Kaede and KikGR.
AB  - The phasor global analysis algorithm is common for fluorescence lifetime
      applications, but has only been recently proposed for spectral analysis. Here the
      phasor representation and fingerprinting is exploited in its second harmonic to
      determine the number and spectra of photo-activated states as well as their
      conversion dynamics. We follow the sequence of photo-activation of proteins over
      time by rapidly collecting multiple spectral images. The phasor representation of
      the cumulative images provides easy identification of the spectral signatures of
      each photo-activatable protein.

PMID- 24040514
TI  - A Design Full of Holes: Functional Nanofilm-Coated Microdomains in Alginate
      Hydrogels.
AB  - This study demonstrates the successful manufacture and functional
      characterization of alginate hydrogels containing a variety of encapsulates
      within polyelectrolyte multilayer-coated micropores. These microporous alginate
      (MPA) hydrogels are prepared via one-step internal ionotropic gelation of the
      alginate using polyelectrolyte multilayer-coated CaCO3 microspheres along with
      the weak acid glucono-delta-lactone. Here, successful encapsulation of a model
      macromolecule and fluorescent nanoparticles within microcapsules-distributed
      throughout the larger alginate hydrogel-is confirmed with confocal microscopy,
      while the porous morphology of the MPA hydrogels is examined with scanning
      electron microscopy. Hydrogels constructed with uncoated CaCO3 microspheres
      release their contents into the surrounding environment, while those constructed
      with polyelectrolyte multilayer-coated CaCO3 microspheres retain the materials
      within the pores. MPA hydrogels containing the model enzyme glucose oxidase
      retained activity and are capable of reacting with small molecules from the
      external environment. The ability to encapsulate an assortment of functional
      materials within a moldable, biocompatible alginate matrix gives this approach
      great flexibility and potential in a wide variety of biomedical applications.

PMID- 24040515
TI  - Prognostic significance of miR-194 in endometrial cancer.
AB  - Endometrial cancer (EC) is the leading malignant tumor occurring in the female
      genital tract and some subtypes are highly invasive and metastatic. miRNAs are
      small non-coding RNAs that have a broad impact on cancer progression. In
      particular, miR-194 regulates epithelial to mesenchymal transition (EMT) by
      suppressing the expression of BMI-1 in EC. In this retrospective study, the
      clinical significance of miR-194 was investigated in archival EC specimens. We
      extracted total RNA from thirty-two EC samples and quantified the expression
      level of miR-194. We discovered that the expression level of miR-194 was
      significantly (P = 0.03) lower in type I EC patients with more advanced stage. In
      addition, patients with higher miR-194 levels have better prognosis than those
      with lower miR-194 levels (P = 0.0067; Cut-off value of miR-194 = 0.3). These
      results indicate that miR-194 has potential to serve as prognostic biomarker for
      EC patients. 

PMID- 24040516
TI  - Capillary recruitment in a theoretical model for blood flow regulation in
      heterogeneous microvessel networks.
AB  - In striated muscle, the number of capillaries containing moving red blood cells
      increases with increasing metabolic demand. This phenomenon, termed capillary
      recruitment, has long been recognized but its mechanism has been unclear. Here, a
      theoretical model for metabolic blood flow regulation in a heterogeneous network
      is used to test the hypothesis that capillary recruitment occurs as a result of
      active control of arteriolar diameters, combined with unequal partition of
      hematocrit at diverging microvascular bifurcations. The network structure is
      derived from published observations of hamster cremaster muscle in control and
      dilated states. The model for modulation of arteriolar diameters includes length
      tension characteristics of vascular smooth muscle and responses of smooth muscle
      tone to myogenic, shear-dependent, and metabolic stimuli. Blood flow is simulated
      including non-uniform hematocrit distribution. Convective and diffusive oxygen
      transport in the network is simulated. Oxygen-dependent metabolic signals are
      assumed to be conducted upstream from distal vessels to arterioles. With
      increasing oxygen demand, arterioles dilate, blood flow increases, and the
      numbers of flowing arterioles and capillaries, as defined by red blood cell flux
      above a small threshold value, increase. Unequal hematocrit partition at
      diverging bifurcations contributes to recruitment and enhances tissue
      oxygenation. The results imply that capillary recruitment, as observed in the
      hamster cremaster preparations, can occur as a consequence of local control of
      arteriolar tone and the resulting non-uniform changes in red blood cell fluxes,
      and provide an explanation for observations of sequential recruitment of
      individual capillaries in response to modulation of terminal arteriolar diameter.

PMID- 24040517
TI  - Video-assisted thoracoscopic surgery.

PMID- 24040518
TI  - VATS and Uniportal VATS: a glimpse into the future.

PMID- 24040519
TI  - Video-assisted thoracoscopic lobectomy-from an experimental therapy to the
      standard of care.

PMID- 24040520
TI  - Techniques of VATS lobectomy.

PMID- 24040522
TI  - Current costs of video-assisted thoracic surgery (VATS) lobectomy.
AB  - Video-assisted thoracoscopic lobectomy has many benefits over open surgery such
      as smaller incisions, less pain, less blood loss, faster postoperative recovery,
      shortened hospital stay, similar or superior survival rates. In contrast video
      assisted thoracic surgery (VATS) has higher equipment costs, increased operating
      room times, at least initially, and a learning curve for the team. However when
      an experienced surgeon performs the surgery, significant hospital savings
      combined with better outcomes are achieved by video-assisted thoracoscopic
      lobectomy. 

PMID- 24040521
TI  - Contraindications of video-assisted thoracoscopic surgical lobectomy and
      determinants of conversion to open.
AB  - Since the introduction of anatomic lung resection by video-assisted thoracoscopic
      surgery (VATS) was introduced 20 years ago, VATS has experienced major advances
      in both equipment and technique, introducing a technical challenge in the
      surgical treatment of both benign and malignant lung disease. The demonstrated
      safety, decreased morbidity, and equivalent efficacy of this minimally invasive
      technique has led to the acceptance of VATS as a standard surgical modality for
      early-stage lung cancer and increasing application to more advanced disease.
      However, only a minority of lobectomies are performed using the VATS technique,
      likely owing to concern for intraoperative complications. Optimal operative
      planning, including obtaining baseline pulmonary function tests with diffusion
      measurements, positron emission tomography and/or computed tomography scans,
      bronchoscopy, and endobronchial ultrasound or mediastinoscopy, can be used to
      anticipate and potentially prevent the occurrence of complications. With
      increasing focus on operative planning, as well as comfort and experience with
      the VATS technique, the indications for which this technique is used has grown.
      As such, the absolute contraindications have narrowed to inability to tolerate
      single lung ventilation, inability to achieve complete resection with lobectomy,
      T3 or T4 tumors, and N2 or N3 disease. However, as VATS lobectomy has been
      applied to more advanced stage disease, the rate of conversion to open
      thoracotomy has increased, particularly early in the surgeon's learning curve.
      Causes of conversion are generally classified into four categories:
      intraoperative complications, technical problems, anatomical problems, and
      oncological conditions. Though it is difficult to anticipate which patients may
      require conversion, it appears that these patients do not suffer from increased
      morbidity or mortality as a result of conversion to open thoracotomy. Therefore,
      with a focus on a safe and complete resection, conversion should be regarded as a
      means of completing resections in a traditional manner rather than as a surgical
      failure. 

PMID- 24040523
TI  - Indication for VATS sublobar resections in early lung cancer.
AB  - When dealing with early non-small cell lung cancer (NSCLC) sublobar resections
      still remain part of the surgical armamentarium. In selected patients with lung
      cancer, the combination of the potential benefits of parenchyma sparing
      procedures to the limited trauma provided by Video Assisted Thoracic Surgery
      (VATS) techniques can become very appealing. Two main groups are included: non
      anatomical (wedges) and anatomical (segmentectomies) excisions. We describe the
      techniques, results and potential indications of both of these techniques. 

PMID- 24040524
TI  - Totally thoracoscopic pulmonary anatomic segmentectomies: technical
      considerations.
AB  - BACKGROUND: While video-assisted thoracic surgery (VATS) lobectomies are being
      increasingly accepted, VATS segmentectomies are still considered as technically
      challenging. With the renewed interest for sublobar resection in the management
      of early stage lung carcinomas, the thoracoscopic approach may have a major role
      in a near future. We report our technique and results. PATIENTS AND METHODS:
      Totally thoracoscopic anatomic segmentectomiy, i.e., using only endoscopic
      instrumentation and video-display without utility incision, was attempted on 117
      patients (51 males and 66 females), aged 18 to 81 years (mean: 62 years). The
      indication was a clinical N0 non-small cell lung carcinoma in 69 cases, a
      solitary metastasis in 17 cases and a benign lesion in 31 cases. The following
      segmentectomies were performed: right apicosuperior [26] right superior [10],
      right basilar [18], lingula sparing left upper lobectomy [15], left apicosuperior
      [11], lingula [7], left superior [14], left basilar [13] and subsegmental
      resection [3]. Segmentectomy was associated with a radical lymphadenectomy in 69
      cases. RESULTS: There were 5 conversions to thoracotomy. The mean operative time
      was 181+/-52 minutes, the mean intraoperative blood loss was 77+/-81 cc. There
      were 12 postoperative complications (11.7%). The median postoperative stay was
      5.5+/-2.2 days. Out of the 69 patients operated on for a cN0 lung carcinoma, 6
      were finally upstaged. CONCLUSIONS: Totally thoracoscopic anatomic pulmonary
      segmentectomies are feasible and have a low complication rate.

PMID- 24040525
TI  - Teaching video-assisted thoracic surgery (VATS) lobectomy.
AB  - Video-assisted thoracic surgery (VATS) lobectomy has become the standard of care
      for early stage lung cancer throughout the world. Teaching this complex procedure
      requires adequate case volume, adequate instrumentation, a committed operating
      room team and baseline experience with open lobectomy. We outline what key
      maneuvers and steps are required to teach and learn VATS lobectomy. This is most
      easily performed as part of a thoracic surgery training program, but with
      adequate commitment and proctoring, there is no reason experienced open surgeons
      cannot become proficient VATS surgeons. We provide videos showing the key
      portions of a subcarinal lymph node dissection, posterior hilar dissection of the
      right upper lobe, fissureless right middle lobectomy, and fissureless left lower
      lobectomy. These videos highlight what we feel are important principals in VATS
      lobectomy, i.e., N2 and N1 lymph node dissection, fissureless techniques, and
      progressive responsibility of the learner. Current literature in simulation of
      VATS lobectomy is also outlined as this will be the future of teaching in VATS
      lobectomy. 

PMID- 24040526
TI  - History and indications of uniportal pulmonary wedge resections.

PMID- 24040527
TI  - Geometrical characteristics of uniportal VATS.
AB  - In terms of accuracy and efficacy Uniportal Video-Assisted Thoracic Surgery
      (VATS) resections are comparable to standard VATS. In standard three-ports VATS,
      the geometric configuration of a parallelogram generates interference with the
      optical source, creating a plane with a torsion angle not favorable on the flat
      two-dimensional vision of currently available monitors. The potential advantages
      of single-port VATS approach include not only the one intercostal space incision
      (reduction of postoperative pain) but also a translational approach of VATS
      instruments along a sagittal plane. Accordingly, the Uniportal approach enables
      VATS instruments to draw two parallel lines on the plane, bringing them to
      approach the target lesion from a caudo-cranial perspective thus achieving a
      projective plane. As a consequence, taking advantage of the unique spatial
      features specific to uniportal VATS, the surgeon is enabled to bring the
      operative fulcrum inside the chest to address the target lesion in a fashion
      similar to open surgery. 

PMID- 24040528
TI  - Uniportal VATS for pneumothorax and interstitial lung disease.
AB  - The algorithms for the management of primary spontaneous pneumothorax (PSP)
      consider the surgical approach as the recommended treatment after the first
      recurrent episode. Surgical lung biopsy should be performed in order to reach the
      specific diagnostic definition in case of interstitial lung disease (ILD). The
      uniportal video-assisted thoracic surgery (VATS) has been proposed as an
      innovative minimally invasive approach for performing the optimal surgical
      management in both PSP and ILD. The aim of the present review is to describe and
      discuss this operative technique, as a valuable option for treating the above
      mentioned thoracic diseases. To this purpose, we herein describe the theoretical
      and practical aspects of the uniportal VATS technique (with the support of two
      specific videos) and review the literature inherent to the use of this approach
      for managing PSP and ILD, demonstrating that this is a well defined and
      standardized surgical technique for performing several intra-thoracic operation
      and, particularly, an effective approach for treating PSP and for managing
      patients affected by ILD. 

PMID- 24040529
TI  - Uniportal VATS in Asia.
AB  - The history of uniportal Video-assisted thoracic surgery (VATS) stretches back
      almost a decade with the treatment of simple thoracic conditions. As the
      technique matures with increasing ability to tackle the full spectrum of thoracic
      surgical diseases, most notably major lung resections for lung tumours, the
      spread of uniportal VATS across the globe has been phenomenal. VATS centres in
      Asia are now performing uniportal VATS, and developing their individual styles
      and techniques with great successes. The enthusiasm from surgeons, demand from
      patients, as well as the dynamism and diversity of uniportal VATS in the region
      have helped fuel this excitement and change. The 1st Asian Single Port VATS
      Symposium in 2013 heralded the beginning of academic exchange between uniportal
      VATS centres in Asia and experts from around the world. Wetlabs in the region
      will provide further training for thoracic surgeons interested in super
      specializing in uniportal VATS. The future of this approach will hinge on good
      regional collaboration, research and training. 

PMID- 24040530
TI  - Uniportal video-assisted thoracoscopic anatomic segmentectomy.

PMID- 24040531
TI  - Uniportal video-assisted thoracoscopic lobectomy.
AB  - Over the past two decades, video-assisted thoracic surgery (VATS) has
      revolutionized the way thoracic surgeons diagnose and treat lung diseases. The
      major advance in VATS procedures is related to the major pulmonary resections.
      The best VATS technique for lobectomy has not been well defined yet. Most of the
      authors describe the VATS approach to lobectomy via 3 to 4 incisions but the
      surgery can be performed by only one incision with similar outcomes. This single
      incision is the same as we normally use for VATS lobectomies performed by double
      or triple port technique with no rib spreading. As our experience with VATS
      lobectomy has grown, we have gradually improved the technique for a less invasive
      approach. Consequently the greater the experience we gained, the more complex the
      cases we performed were, hence expanding the indications for single-incision
      thoracoscopic lobectomy. 

PMID- 24040532
TI  - Uniportal video-assisted thoracoscopic pneumonectomy.
AB  - Video-assisted thoracoscopic surgery (VATS) was introduced nearly 2 decades ago
      and has experienced an exponential increase for lung cancer treatment. A
      pneumonectomy can be performed by video-assisted thoracoscopic surgery and the
      lung usually fits through the incision as usually used for VATS lobectomy. The
      most common approach for pneumonectomy is undertaken with 3 or 4 incisions,
      including a utility incision of about 3-6 cm. However, this resection is amenable
      by using only a single utility-incision. This chapter describes the technique for
      pneumonectomies by single-incision thoracoscopic approach with no rib spreading. 

PMID- 24040533
TI  - Video-assisted thoracoscopic lobectomy for non-small cell lung cancer in patients
      with severe chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To assess the feasibility, safety and long-term outcomes of video
      assisted thoracic surgery (VATS) lobectomy for the treatment of non-small cell
      lung cancer (NSCLC) in patients with severe chronic obstructive pulmonary disease
      (COPD). METHODS: The clinical data of patients with NSCLC and severe COPD
      (preoperative FEV1% <50%) who underwent VATS lobectomy from January 2000 to
      January 2011 were retrospectively analyzed to identify their demographic
      parameters, postoperative complications and outcomes. RESULTS: The preoperative
      FEV1/FVC was <70% and FEV1% <50% in all 61 patients in this study, with a mean
      preoperative FEV1 of 0.99 L (0.54-1.58 L) and mean FEV1% of 38.4% (22-49.82%).
      All of the 61 patients underwent the VATS lobectomy or sleeve resection plus
      systemic lymph node dissection. The mean operative time was 218 minutes (120-355
      minutes), with a mean intraoperative blood loss of 342 mL (50-1,600 mL). None of
      the patients converted to thoracotomy. Multivariate statistical analysis revealed
      that age and TNM staging after tumor resection were independent predictive
      factors for the 5-year survival in those patients (P=0.014 and 0.013).
      CONCLUSIONS: With preoperative imaging studies, pulmonary function assessment and
      target positioning, VATS lobectomy can be safely and effectively performed for
      patients with NSCLC and severe COPD to achieve a satisfying long-term survival
      outcome.

PMID- 24040534
TI  - Thoracoscopic minimally invasive surgery for non-small cell lung cancer in
      patients with chronic obstructive pulmonary disease.
AB  - OBJECTIVE: To determine the incidence of peri-operative complications in non
      small cell lung cancer (NSCLC) patients with co-existent chronic obstructive
      pulmonary disease (COPD) who undergo lung resection via traditional and minimally
      invasive techniques. METHODS: A retrospective analysis was conducted of 152 NSCLC
      patients with COPD who underwent thoracoscopic minimally invasive surgery.
      Particular attention is given to the relationship between disease severity or
      surgical approach and the incidence of complications. RESULTS: THE PREVALENCE OF
      RESPIRATORY AND CARDIAC COMPLICATIONS WAS SIGNIFICANTLY HIGHER IN PATIENTS WITH
      SEVERE/EXTREMELY SEVERE COPD THAN THOSE WITH MILD TO MODERATE COPD (RESPIRATORY
      COMPICATIONS: 37.3% vs. 20.4%, P=0.022; cardiac complications: 16.9% vs. 6.5%,
      P=0.040). Patients who underwent complete-video assisted thoracoscopic surgery (c
      VATS) had a significantly lower overall morbidity of adverse reactions than those
      who had undergone VATS major resection (26.3% vs. 42.1%, P=0.044). Among patients
      with severe/extremely severe COPD, there was no significant difference in the
      incidence of any complication between the lobectomy group and wedge resection
      group (38.8% vs. 70.0%, P=0.072). Overall, the occurrence of adverse reactions
      was significantly lower in patients who underwent c-VATS than in those who had
      undergone VATS major resection surgery (34.2% vs. 61.9%, P=0.038). CONCLUSIONS:
      VATS techniques are suitable for COPD patients and are demonstrated here to lower
      the incidence of post-operative complications when compared with more invasive
      approaches.

PMID- 24040535
TI  - Feasibility of complete video-assisted thoracoscopic surgery following
      neoadjuvant therapy for locally advanced non-small cell lung cancer.
AB  - OBJECTIVE: To explore the feasibility of complete video-assisted thoracoscopic
      surgery (c-VATS) following neoadjuvant therapy (chemotherapy, targeted therapy
      and radiotherapy, either alone or in combination) for the treatment of patients
      with non-small cell lung cancer (NSCLC). METHODS: The clinical data of 43 NSCLC
      patients undergoing c-VATS following neoadjuvant therapy were retrospectively
      analyzed, including the preoperative functional indicators, staging, concurrent
      diseases, surgical techniques, operation time, number of lymph nodes dissected
      and postoperative drainage time and quantity, postoperative hospital stay,
      postoperative complications, and survival. RESULTS: From January 2006 to March
      2012, a total of 43 patients with stage IIA-IIIB NSCLC were included in this
      study (IIIA: 27 cases, 62.8%; IIIB: 11 cases, 25.6%), including 32 males (74.4%)
      and 11 females (25.6%). Forty-two patients were operated successfully, 28
      underwent pulmonary lobectomies (including 9 bronchial sleeve resections), 5 had
      double lobectomies, 5 had wedge resections, and 4 had total pneumonectomies.
      Seven patients were referred to undergo Hybrid VATS (7/42, 16.7%). The mean
      length of the operation was 160.48+/-16.52 min (range, 130-180 min); the
      intraoperative blood loss was 253.57+/-117.08 mL; the number of lymph nodes
      dissected was 16.88+/-10.93; the postoperative drainage time was 1-7 d (mean:
      2.62+/-0.96 d); and the postoperative hospital stay was 3-7 d (mean: 5.45+/-1.30
      d). The incidence of postoperative complications was 9.5% (4/42), and the
      perioperative mortality was 2.4% (1/42). The 1-, 2-, and 3-year overall survival
      rates were 94%, 79%, and 65%, respectively. CONCLUSIONS: c-VATS following
      neoadjuvant therapy is safe and feasible for the treatment of locally advanced
      NSCLC.

PMID- 24040536
TI  - Current surgical management of melanoma metastases to the lung.

PMID- 24040537
TI  - Right, middle, and lower bronchial sleeve lobectomy by video-assisted thoracic
      surgery.

PMID- 24040538
TI  - Video-assisted thoracic surgery (VATS) right upper lobectomy.
AB  - Video-assisted thoracic surgery (VATS) plays supplementary role to the open
      surgery in the thoracic surgery. As the clinical education and VATS procedure
      developed, more patients are willing to take VATS surgery than open surgery if
      the condition permits. With the help of proficiency and HD thoracoscopic
      instruments, nearly all open surgery can be done, theoretically, in VATS either.
      In addition the better accessibility to the operative video and academic meeting
      greatly propel the prevalence of VATS surgery. Here I present a VATS right upper
      lobectomy case to communicating operative techniques. 

PMID- 24040539
TI  - Video-assisted thoracoscopic right lower lobectomy: the Tianjin Chest Hospital
      experience.
AB  - Video-assisted thoracoscopic surgery (VATS) is now well established as an
      alternative to open thoracotomy for major pulmonary resections of bronchogenic
      carcinoma and benign disease. More than 900 VATS major pulmonary resections have
      been performed in our center over the last 5 years and we here describe our
      method for VATS right lower lobectomy. In our center, procedures is performed
      with 3 incisions. For right lower lobes, the patient is placed into the left
      lateral position. The inferior pulmonary vein is dissected and divided with an
      endoscopic vascular stapler. The pulmonary artery branches to right lower lobe
      are divided with endoscopic staplers, and the lower lobe bronchus is divided at
      last. Throughout the procedure, hilar and mediastinal lymph nodes are dissected
      and removed in NSCLC. According to our experience, VATS is safe and feasible in
      thoracotomy for major pulmonary resections. 

PMID- 24040540
TI  - Video assistant thoracoscopic (VATS) lobectomy: right lower lobe.
AB  - The 60-year-old female had a nodule in the right lower lobe of the lung, which
      was identified as a tumor by CT and PET-CT. Then the right lower lobectomy was
      performed. The posterior trocar placement, different from other surgery, is in
      the 5th intercostals space in the anterior latissimus dorsi, which can be built
      by a small incision when operation is needed. There is a vessel heteromorphosis
      that the inferior pulmonary vein and the mid pulmonary vein share the same stem.
      Also, this patient has many intumescentia lymph nodes. We can see, the lymph
      nodes can be ablated completely by VATS. 

PMID- 24040541
TI  - Video-assisted thoracoscopic superior segmentectomy of the right lower lobe.
AB  - Sublobar resections are still controversial for lung cancer, but for patients who
      can't tolerate lobectomy, such as those suffering from cardiopulmonary
      comorbidities and aged people, sublobar resections are better choices. Lobectomy
      and sublobar resections have similar surgical effect on patients with tumors <=2
      cm. A 64-year-old patient with chronic obstructive pulmonary disease (COPD) and
      poor pulmonary function on pre-operation evaluation underwent thoracoscopic
      superior segementectomy with systemic mediastinal lymph node dissection. Three
      holes were adopted, the major operation hole was a 3 cm mini-incision in the
      4(th) intercostal space of anterior axillary line. The patient has recovered well
      after the surgery. 

PMID- 24040542
TI  - Video-assisted thoracoscopic surgery (VATS) right upper lobectomy and systematic
      lymph node dissection for lung cancer.
AB  - Video-assisted thoracoscopic surgery (VATS) represents a new trend in the
      development of minimally invasive thoracic surgery. When applied in lung cancer
      surgeries, VATS can be used for both pulmonary lobectomy and regional lymph node
      dissection. Currently the main concerns are focused on the completeness of lymph
      node dissection for lung cancer and the safety of surgery. The lymph node
      dissection includes two parts: (I) dissection of interlobar and hilar lymph
      nodes; and (II) dissection of mediastinal lymph nodes. The demonstrated surgical
      procedures are featured by: (I) the interlobar and hilar lymph nodes are not
      removed separately; rathr, they are taken out en bloc with the pulmonary lobes
      during the surgery; and (II) systematic lymph node dissection, instead of
      systematic sampling, is applied for the removal of mediastinal lymph nodes. Also,
      during the fully anatomical resection, each blood vessel and bronchus underwent
      anatomical dissociation, indicating that this surgery is safe. 

PMID- 24040543
TI  - Radical resection of right upper lung under complete video-assisted thoracoscopic
      surgery.

PMID- 24040544
TI  - Complete VATS right upper lobectomy plus lymphadenectomy.

PMID- 24040545
TI  - Left upper lobectomy.
AB  - This is a 32-year-old woman with a left peripheral lung lesion about 3 cm in
      diameter found by physical examination. Lung cancer of the left upper lobe is
      suspected in preoperative diagnosis. 

PMID- 24040546
TI  - VATS left upper lobectomy.
AB  - A 60-year-old female patient was admitted due to multiple ground-glass nodules in
      the left upper lobe, which was found on her health screening 20 days ago.
      Preoperative examinations showed no obvious abnormality. Also, no distant
      metastasis was found during the preoperative examinations, and her heart and lung
      functions could tolerate the lobectomy. Chest computed tomography (CT) showed
      multiple ground-glass nodules on the left lung, which were considered to be early
      malignant lesions; In addition, no remarkably swollen lymph node was visible in
      the mediastinum. Therefore, VATS left upper lobectomy was performed, and
      intraoperative frozen section confirmed the diagnosis of adenocarcinoma. 

PMID- 24040547
TI  - Complete video-assisted thoracoscopic surgery upper left bronchial sleeve
      lobectomy.
AB  - This video demonstrates a case undergoing complete video-assisted thoracoscopic
      surgery (VATS) upper left bronchial sleeve lobectomy. The 18-year-old female
      patient was admitted for recurrent cough and intermittent hemoptysis for one
      month. Chest CT scan showed a neoplasm in the left main bronchus and the left
      upper lobe bronchus. Bronchoscopic biopsy indicated mucinous epithelial cancer.
      Based on the chest CT findings, the left lower lung was not affected. To preserve
      normal lung tissue and minimize the loss of lung function, we decided to perform
      this surgical procedure. A three-port technique was conducted, in which the
      hypoplastic oblique fissure, the left upper pulmonary vein, and the upper lobe
      branch of the left pulmonary artery were initially treated under complete VATS.
      Bronchial sleeve lobectomy of the upper lobe of the left lung was finally carried
      out. The key to success was the end-to-end anastomosis between the left main
      bronchus and the lower left bronchus under thoracoscope. The deep location of the
      operative field partly hidden under the left pulmonary artery trunk during
      bronchial anastomosis made it even more difficult to operate thoracoscopically.
      To improve exposure of the operative field, we managed to raise the left main
      bronchus by passing two 1-0 silk sutures, respectively ligated with both sides of
      the posterior wall of the left main bronchus, through the anterior and posterior
      chest walls using a crochet needle. Similarly, a 1-0 silk suture was advanced
      through the posterior chest wall with a crochet needle to lift the trunk of the
      left pulmonary artery. In this way, a widely open, exposed field was achieved.
      Postoperative recovery was smooth. Chest X-ray showed good expansion of the left
      lung. Bronchoscopy indicated a patent anastomosis. The patient was discharged
      after two weeks. In conclusion, complete VATS bronchial sleeve lobectomy is a
      minimally invasive approach for thorough removal of tumor lesions while sparing
      as most normal lung tissue as possible, which avoids pneumonectomy and satisfies
      the psychological and physiological needs of patients. 

PMID- 24040548
TI  - Video-assisted thoracic surgery (VATS) left upper sleeve lobectomy with partial
      pulmonary artery resection.
AB  - Compare with pneumonectomy, sleeve lobectomy has advantage in long-term outcomes
      and cost-effective measures. As a result, sleeve lobectomy procedure is
      considered and practiced as the standard therapy for central lung cancers which
      are anatomically suitable regardless of lung function. In some cases, the lesion
      invades hilar and mediastinal vessels, the surgeon may faces more technically
      challenging in vascular reconstruction procedures together with the sleeve
      lobectomy procedure. The advent of minimally invasive surgery brings numerous
      advantages, such as shorter hospital stay, alleviated post-operative pain, faster
      recover and so on, to the patient. In return, it did demands all the surgeons to
      master the VATS surgery operative skill to meet the patient's expectation.
      Although mirror the pathway of open sleeve surgery, the video-assisted bronchial
      sleeve lobectomy (VABSL) brings numerous obstacles for the surgeon: One needs to
      accommodate transmission from direct-view to locally 2D screen, from multi-angle
      multi-direction operation field to one directional operation field, before he can
      adapt to the VATS operative skill. In addition, VATS surgery did have its'
      learning curve for the surgeon and the assistant. Here we present a video of a
      patient underwent sleeve lobectomy with partial pulmonary artery resection for
      communicating operative techniques. 

PMID- 24040549
TI  - Video-assisted left upper bronchial sleeve lobectomy.
AB  - Compare with pneumonectomy, sleeve lobectomy has advantage in long-term outcomes
      and cost-effective measures. As a result, sleeve lobectomy procedure is
      considered and practiced as the standard therapy for central lung cancers which
      are anatomically suitable regardless of lung function. The advent of minimally
      invasive surgery brings numerous advantages, such as shorter hospital stay,
      alleviated post-operative pain, faster recover and so on, to the patient. In
      return, it did demands all the surgeons to master the video-assisted thoracic
      surgery (VATS) operative skill to meet the patient's expectation. Although mirror
      the pathway of open sleeve surgery, the video-assisted bronchial sleeve lobectomy
      (VABSL) brings numerous obstacles for the surgeon: one needs to accommodate
      transmission from direct-view to locally 2D screen, from multi-angle multi
      direction operation field to one directional operation field, before he can adapt
      to the VATS operative skill. In addition, VATS surgery did have its' learning
      curve for the surgeon and the assistant. Here we present a video of a patient
      underwent sleeve lobectomy for communicating operative techniques. 

PMID- 24040550
TI  - Right lower lobe resection.

PMID- 24040551
TI  - Complete thoracoscopic lobectomy and mediastinal lymph node dissection.
AB  - To evaluate the complete thoracoscopic lower right lobectomy and mediastinal
      lymph node. During the surgery, the lower right pulmonary artery and vein,
      bronchi and lymph nodes were treated using a unidirectional approach. Eight
      stations (2, 3, 4, 7, 8, 9, 10 and 11) of lymph nodes were dissected completely
      en bloc. Repeated stretch and flipping was avoided in this procedure, which was
      beneficial for the unaffected side of the lung. The operation of lymph node
      dissection was completed thoroughly in accordance with standard principles. 

PMID- 24040552
TI  - Unidirectionally progressive resection of lower right lung cancer under video
      assisted thoracoscopy.
AB  - The surgery is performed under general anesthesia with double-lumen endotracheal
      intubation. The patient is placed in a 90-degree position lying on the unaffected
      side. An approximately 1.5-cm observation port is created in the 7th intercostal
      space between the middle and anterior axillary lines, an approximately 4-cm
      working port in the 4th intercostal space between the anterior axillary line and
      the midclavicular line, and an approximately 1.5-cm auxiliary port in the 9th
      intercostal space between the posterior axillary line and the subscapular line.
      The operator stands in front of the patient, manipulating the endoscopic
      instruments while watching the monitor. SURGICAL PROCEDURE: since the patient has
      right lower lung cancer, a unidirectional procedure is adopted for the surgery,
      in which the layers of structure are treated one after another until the fissure
      from a single direction through the working port. Hence, the pulmonary vein,
      bronchi, pulmonary artery and the poorly developed fissure of the right lower
      lobe are treated successively during lobectomy. The vessels, bronchi and fissures
      are cut using an endoscopic linear stapler or the Hemolock clips. The resected
      lobe is placed into a size 8 sterile glove and retrieved through the working port
      to prevent contamination of the chest incision by any tumor tissue. Mediastinal
      lymph node dissection is performed at the end.

PMID- 24040553
TI  - Right middle-lower lobectomy by Video-assisted Thoracic Surgery (VATS).

PMID- 24040554
TI  - VATS left upper lobe posterior segmentectomy.
AB  - A 56-year-old male patient was admitted due to one small pulmonary nodule in the
      posterior segment of left upper lobe. Preoperative examinations showed no distant
      metastasis, pulmonary ventilation function and small airway function were highly
      damaged and could not tolerate lobectomy. Chest computed tomography (CT) showed
      one small pulmonary nodules on the posterior segment of left lung, which was
      considered to be early malignant lesions. In addition, no remarkably swollen
      lymph node was visible in the mediastinum. Therefore, video-assisted thoracic
      surgery (VATS) left upper lobe posterior segmentectomy was performed, and
      intraoperative frozen section confirmed the diagnosis of adenomatous hyperplasia
      of alveolar epithelial. Sequential dissection (or, single-direction approach) was
      applied in this surgery to avoid frequent turn-over of the lung lobes and shift
      of visual angle during the procedures. The Electric hook used in this surgery
      enables careful dissection and dissociation, with clear visual field and small
      blood loss. 

PMID- 24040555
TI  - VATS right middle lobectomy.
AB  - A 48-year-old patient was admitted due to space occupying lesion in the right
      middle lobe, which was found by her healthy examination 1 month ago. Preoperative
      examinations displayed that the cardiopulmonary functions of the patient was
      normal, and chest computer tomography (CT) showed lesion located in the
      peripheral lung, diameter of the lesion was 3 cm, there was evidence that lymph
      node was visible in the mediastinum and no metastasis. Video-assisted thoracic
      surgery (VATS) right middle lobectomy was preformed, and intraoperative frozen
      section ensures the diagnosis of adenocarcinoma. 

PMID- 24040556
TI  - Bronchial anastomosis using complete continuous suture in video-assisted thoracic
      surgery sleeve lobectomy.

PMID- 24040557
TI  - Video-assisted thoracic surgery right sleeve lobectomy.

PMID- 24040558
TI  - VATS right upper lobectomy.
AB  - Standard thoracotomy has been considered as the classic approach and only choice
      for the diagnosis and treatment of certain thoracic diseases especially in
      patients with peripheral lung cancer. Video-assisted thoracic surgery (VATS) is a
      new minimally invasive thoracic surgery through small incisions in the
      intercostal muscle of chest wall by using modern camera technology, high-tech
      equipment and surgical instrument. Consequently, VATS has become the preferred
      main method for peripheral lung cancer in the last two decades. The aim of the
      present paper is to describe and discuss the operative techniques of VATS for
      right upper lobectomy (RUL). 

PMID- 24040559
TI  - Video-assisted thoracic surgery right upper lobectomy and lymph node dissection.
AB  - We described a 55-year-old male smoking patient, who came to our institute with
      the diagnosis of a right upper lobe lesion. Computed tomographic (CT) guided
      biopsy confirmed a diagnosis of lung adenocarcinoma. The preoperative clinical
      diagnosis was stage I primary lung adenocarcinoma. The standard three-port video
      assisted thoracoscopy surgery (VATS) was performed in this case. After the
      resection of the right upper lobe, the 2(nd), 4(th), and 7(th) groups of
      lymphatic nodes were removed with Harmonic scalpel. A closed drainage catheter
      was placed adjacent to the lateral chest wall through the port in the 7th
      intercostal space. Postoperative pathologic diagnosis was T2aN0M0 adenocarcinoma.

PMID- 24040560
TI  - Complete video-assisted thoracic surgery right upper lobe sleeve resection.

PMID- 24040561
TI  - Highlights in lung cancer: explore treatment and care for lung cancer with world
      known experts.

PMID- 24040562
TI  - Highlights in management of early stage non-small cell lung cancer.

PMID- 24040565
TI  - Is one better than two?

PMID- 24040564
TI  - Blood Cells and Interferon-Gamma Levels Correlation in Latent Tuberculosis
      Infection.
AB  - The Mycobacterium tuberculosis (M. tb) infection is largely spread in world's
      population. Most infected individuals develop latent tuberculosis infection
      (LTBI). Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs)
      are the available tests to detect the infection. It has been reported that some
      individuals take a longer period of time to develop the infection than others
      with the same exposure level. It is suggested that the innate immunity, in which
      neutrophils have an important protective role, is responsible for this. Many
      hematologic abnormalities have been described as common findings during severe
      disease. To investigate if these changes are related to LTBI development and if
      they interfere in TST and IFN-gamma production, we recruited 88 household
      contacts of tuberculosis (TB) pulmonary patients and compared blood cell counts
      with these tests' results. There were no statistically significant changes in
      hemoglobin, hematocrit, platelets, global leukocyte, neutrophils, basophils,
      eosinophils, typical lymphocytes, atypical lymphocytes, and monocytes counts
      between infected and noninfected individuals. Also, there was no correlation
      between TST or IGRA and blood cell counts. These results suggest that blood cell
      counts are not LTBI markers and do not interfere in TST results or IFN-gamma
      levels obtained by IGRA.

PMID- 24040566
TI  - Development of animal experimental periodontitis models.
AB  - PURPOSE: An animal periodontitis model is essential for research on the
      pathogenesis and treatment of periodontal disease. In this study, we have
      introduced a lipopolysaccharide (LPS) of a periodontal pathogen to the alveolar
      bone defect of experimental animals and investigated its suitability as a
      periodontitis model. METHODS: Alveolar bone defects were made in both sides of
      the mandibular third premolar region of nine beagle dogs. Then, the animals were
      divided into the following groups: silk ligature tied on the cervical region of
      tooth group, Porphyromonas gingivalis LPS (P.g. LPS)-saturated collagen with silk
      ligature group, and no ligature or P.g. LPS application group as the control. The
      plaque index and gingival index were measured at 0 and 4 weeks postoperatively.
      The animals were then euthanized and prepared for histologic evaluation. RESULTS:
      The silk ligature group and P.g. LPS with silk ligature group showed a
      significantly higher plaque index at 4 weeks compared to the control (P<0.05). No
      significant difference was found in the plaque index between the silk ligature
      group and P.g. LPS with silk ligature group. The P.g. LPS with silk ligature
      group showed a significantly higher gingival index compared to the silk ligature
      group or the control at 4 weeks (P<0.05). Histologic examination presented
      increased inflammatory cell infiltration in the gingival tissue and alveolar bone
      of the P.g. LPS with silk ligature group. CONCLUSIONS: An additional P.g. LPS
      saturated collagen with silk ligature ensured periodontal inflammation at 4
      weeks. Therefore, P.g. LPS with silk ligature application to surgically created
      alveolar bone defects may be a candidate model for experimental periodontitis.

PMID- 24040567
TI  - What is the effect of initial implant position on the crestal bone level in flap
      and flapless technique during healing period?
AB  - PURPOSE: The level of the implant above the marginal bone and flap design have an
      effect on the bone resorption during the healing period. The aim of this study is
      to detect the relationship between the level of the implant at the implant
      placement and the bone level at the healing period in the mesial and distal side
      of implants placed with flapless (FL) and full-thickness flap (FT) methods.
      METHODS: Twenty-two nonsubmerged implants were placed with the FL and FT
      technique. Periapical radiographs were taken of the patient at implant placement,
      and at 6 and 12 weeks. By using computer software, bone level measurements were
      taken from the shoulder of the healing cap to the first bone implant contact in
      the mesial and distal side of the implant surface. RESULTS: At 6 weeks, the
      correlation between the crestal bone level at the implant placement and crestal
      bone level of the FT mesially was significant (Pearson correlation
      coefficient=0.675, P<0.023). At 12 weeks, in the FT mesially, the correlation was
      nonsignificant (Spearman correlation coefficient=0.297, P<0.346). At 6 weeks in
      the FT distally, the correlation was nonsignificant (Pearson correlation
      coefficient=0.512, P<0.107). At 12 weeks in the FT distally, the correlation was
      significant (Spearman correlation coefficient=0.730, P<0.011). At 6 weeks in the
      FL mesially, the correlation was nonsignificant (Spearman correlation
      coefficient=0.083, P<0.809). At 12 weeks in the FL mesially, the correlation was
      nonsignificant (Spearman correlation coefficient=0.062, P<0.856). At 6 weeks in
      the FL distally, the correlation was nonsignificant (Spearman correlation
      coefficient=0.197, P<0.562). At 12 weeks in the FL distally, the correlation was
      significant (Pearson correlation coefficient=0.692, P<0.018). CONCLUSIONS: A
      larger sample size is recommended to verify the conclusions in this preliminary
      study. The bone level during the healing period in the FT was more positively
      correlated with the implant level at implant placement than in the FL.

PMID- 24040568
TI  - An analysis on the factors responsible for relative position of interproximal
      papilla in healthy subjects.
AB  - PURPOSE: This study examined the factors that can be associated with the
      appearance of the interproximal papilla. METHODS: One hundred and forty-seven
      healthy interproximal papillae between the maxillary central incisors were
      examined. For each subject, a digital photograph and periapical radiograph of the
      interdental embrasure were taken using a 1-mm grid metal piece. The following
      parameters were recorded: the amount of recession of the interproximal papilla,
      contact point-bone crest distance, contact point-cemento-enamel junction (CEJ)
      distance, CEJ-bone crest distance, inter-radicular distance, tooth shape,
      embrasure space size, interproximal contact area, gingival biotype, papilla
      height, and papilla tip form. RESULTS: THE AMOUNT OF RECESSION OF THE
      INTERPROXIMAL PAPILLA WAS ASSOCIATED WITH THE FOLLOWING: 1) increase in contact
      point-bone crest, contact point-CEJ, and CEJ-bone crest distance; 2) increase in
      the inter-radicular distance; 3) triangular tooth shape; 4) decrease in the
      interproximal contact area length; 5) increase in the embrasure space size; and
      6) flat papilla tip form. On the other hand, the amount of gingival recession was
      not associated with the gingival biotype or papilla height. In the triangular
      tooth shape, the contact point-bone crest distance and inter-radicular distance
      were longer, the interproximal contact area length was shorter, and the embrasure
      space size was larger. The papilla tip form became flatter with increasing inter
      radicular distance and CEJ-bone crest distance. CONCLUSIONS: The relative
      position of the interproximal papilla in healthy subjects was associated with the
      multiple factors and each factor was related to the others. A triangular tooth
      shape carries a higher risk of recession of the interproximal papilla because the
      proximal contact point is positioned more incisally and the bone crest is
      positioned more apically. This results in an increase in recession of the
      interproximal papilla and flat papilla tip form.

PMID- 24040569
TI  - The effects of dexamethasone on the apoptosis and osteogenic differentiation of
      human periodontal ligament cells.
AB  - PURPOSE: The purpose of the current study was to examine the effect of
      dexamethasone (Dex) at various concentrations on the apoptosis and mineralization
      of human periodontal ligament (hPDL) cells. METHODS: hPDL cells were obtained
      from the mid-third of premolars extracted for orthodontic reasons, and a primary
      culture of hPDL cells was prepared using an explant technique. Groups of cells
      were divided according to the concentration of Dex (0, 1, 10, 100, and 1,000 nM).
      A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was
      performed for evaluation of cellular viability, and alkaline phosphatase activity
      was examined for osteogenic differentiation of hPDL cells. Alizarin Red S
      staining was performed for observation of mineralization, and real-time
      polymerase chain reaction was performed for the evaluation of related genes.
      RESULTS: Increasing the Dex concentration was found to reduce cellular viability,
      with an increase in alkaline phosphatase activity and mineralization. Within the
      range of Dex concentrations tested in this study, 100 nM of Dex was found to
      promote the most vigorous differentiation and mineralization of hPDL cells. Dex
      induced osteogenic differentiation and mineralization was accompanied by an
      increase in the level of osteogenic and apoptosis-related genes and a reduction
      in the level of antiapoptotic genes. The decrease in hPDL cellular viability by
      glucocorticoid may be explained in part by the increased prevalence of cell
      apoptosis, as demonstrated by BAX expression and decreased expression of the
      antiapoptotic gene, Bcl-2. CONCLUSIONS: An increase in hPDL cell differentiation
      rather than cellular viability at an early stage is likely to be a key factor in
      glucocorticoid induced mineralization. In addition, apoptosis might play an
      important role in Dex-induced tissue regeneration; however, further study is
      needed for investigation of the precise mechanism.

PMID- 24040563
TI  - The role of nuclear bodies in gene expression and disease.
AB  - This review summarizes the current understanding of the role of nuclear bodies in
      regulating gene expression. The compartmentalization of cellular processes, such
      as ribosome biogenesis, RNA processing, cellular response to stress,
      transcription, modification and assembly of spliceosomal snRNPs, histone gene
      synthesis and nuclear RNA retention, has significant implications for gene
      regulation. These functional nuclear domains include the nucleolus, nuclear
      speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal
      body, histone locus body and paraspeckle. We herein review the roles of nuclear
      bodies in regulating gene expression and their relation to human health and
      disease. 

PMID- 24040570
TI  - Efficacy of nonsurgical periodontal therapy on glycaemic control in type II
      diabetic patients: a randomized controlled clinical trial.
AB  - PURPOSE: Diabetes and periodontal disease are two common diseases with high
      prevalence rates. Recent evidence has shown a bidirectional relationship between
      diabetes and periodontitis. The aim of this study was to investigate the effects
      of nonsurgical periodontal therapy on glycemic control in type 2 diabetes
      mellitus patients. METHODS: Sixty subjects aged 35-45 years with blood sugar
      controlled by oral hypoglycaemic agents were randomly divided equally among 3
      groups: group A (scaling, mouthwash, and brushing), group B (mouthwash and
      brushing), and group C (brushing only). Glycated haemoglobin (HbA1c), fasting
      blood sugar (FBS), probing pocket depth (PPD), gingival index (GI), plaque index
      (PI), and the relevant drug history were recorded at baseline and after 3 months
      of intervention. Comparison of the mean difference among the variables was
      performed by parametric and nonparametric tests, which were further evaluated
      using multiple regression analysis. RESULTS: The mean differences between the
      PPD, FBS, HbA1c, GI, and PI in groups A and B were found to be statistically
      significant (P<0.001). Multiple regression analysis in group A showed that out of
      all the independent variables, GI and frequency of drug administration
      independently (b=0.3761 and b=0.598) showed a significantly greater impact on
      HbA1c (R(2)=0.832, P<0.05). CONCLUSIONS: Nonsurgical periodontal therapy can
      effectively decrease HbA1c levels in type 2 diabetes mellitus patients on
      medication.

PMID- 24040571
TI  - Quantitative analysis of periodontal pathogens present in the saliva of geriatric
      subjects.
AB  - PURPOSE: At present, information regarding periodontal disease in geriatric
      patients is scarce. The purpose of this study was to quantify the periodontal
      pathogens present in the saliva of Korean geriatric patients and assess the
      relationship between the bacterial levels and the periodontal condition. METHODS:
      Six putative periodontal pathogens were quantified by using a real-time
      polymerase chain reaction assay in geriatric patient groups (>60 years) with mild
      chronic periodontitis (MCP), moderate chronic periodontitis (MoCP), and severe
      chronic periodontitis (SCP). The copy numbers of Porphyromonas gingivalis,
      Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans,
      Fusobacterium nucleatum, and Prevotella intermedia were measured. RESULTS: It was
      found that the bacterial copy numbers increased as the severity of the disease
      increased from MCP to SCP, except for P. intermedia. For P. intermedia, it was
      found that samples in the MCP group yielded the largest amount. It was also found
      that the quantities of P. gingivalis, T. forsythia, and T. denticola, the so
      called "red complex" bacteria, were lower than those of F. nucleatum, A.
      actinomycetemcomitans, and P. intermedia in all of the samples. CONCLUSIONS:
      Collectively, the results of this study suggest that the levels of P. gingivalis,
      T. forsythia, F. nucleatum, and T. denticola present in saliva are associated
      with the severity of periodontal disease in geriatric patients.

PMID- 24040572
TI  - Effect of quercetin on the production of nitric oxide in murine macrophages
      stimulated with lipopolysaccharide from Prevotella intermedia.
AB  - PURPOSE: Nitric oxide (NO) is a short-lived bioactive molecule that is known to
      play an important role in the pathogenesis of periodontal disease. In the current
      study, we investigated the effect of the flavonoid quercetin on the production of
      NO in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella
      intermedia, a pathogen related to inflammatory periodontal disease, and tried to
      elucidate the underlying mechanisms of action. METHODS: LPS was isolated from P.
      intermedia ATCC 25611 cells by the standard hot phenol-water method. The
      concentration of NO in cell culture supernatants was determined by measuring the
      accumulation of nitrite. Inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1)
      protein expression, phosphorylation of c-Jun N-terminal kinase (JNK) and p38,
      inhibitory kappaB (IkappaB)-alpha degradation, and signal transducer and
      activator of transcription 1 (STAT1) phosphorylation were analyzed via
      immunoblotting. RESULTS: Quercetin significantly attenuated iNOS-derived NO
      production in RAW246.7 cells activated by P. intermedia LPS. In addition,
      quercetin induced HO-1 protein expression in cells activated with P. intermedia
      LPS. Tin protoporphyrin IX (SnPP), a competitive inhibitor of HO-1, abolished the
      inhibitory effect of quercetin on LPS-induced NO production. Quercetin did not
      affect the phosphorylation of JNK and p38 induced by P. intermedia LPS. The
      degradation of IkappaB-alpha induced by P. intermedia LPS was inhibited when the
      cells were treated with quercetin. Quercetin also inhibited LPS-induced STAT1
      signaling. CONCLUSIONS: Quercetin significantly inhibits iNOS-derived NO
      production in murine macrophages activated by P. intermedia LPS via anti
      inflammatory HO-1 induction and inhibition of the nuclear factor-kappaB and STAT1
      signaling pathways. Our study suggests that quercetin may contribute to the
      modulation of host-destructive responses mediated by NO and appears to have
      potential as a novel therapeutic agent for treating inflammatory periodontal
      disease.

PMID- 24040573
TI  - Surface characteristics and bioactivity of an anodized titanium surface.
AB  - PURPOSE: The aim of this study was to evaluate the surface properties and
      biological response of an anodized titanium surface by cell proliferation and
      alkaline phosphatase activity analysis. METHODS: Commercial pure titanium (Ti)
      disks were prepared. The samples were divided into an untreated machined Ti group
      and anodized Ti group. The anodization of cp-Ti was formed using a constant
      voltage of 270 V for 60 seconds. The surface properties were evaluated using
      scanning electron microscopy, X-ray photoelectron spectroscopy, and an image
      analyzing microscope. The surface roughness was evaluated by atomic force
      microscopy and a profilometer. The contact angle and surface energy were
      analyzed. Cell adhesion, cell proliferation, and alkaline phosphatase activity
      were evaluated using mouse MC3T3-E1 cells. RESULTS: The anodized Ti group had a
      more porous and thicker layer on its surface. The surface roughness of the two
      groups measured by the profilometer showed no significant difference (P>0.001).
      The anodized Ti dioxide (TiO2) surface exhibited better corrosion resistance and
      showed a significantly lower contact angle than the machined Ti surface
      (P>0.001). Although there was no significant difference in the cell viability
      between the two groups (P>0.001), the anodized TiO2 surface showed significantly
      enhanced alkaline phosphatase activity (P<0.001). CONCLUSIONS: These results
      suggest that the surface modification of Ti by anodic oxidation improved the
      osteogenic response of the osteoblast cells.

PMID- 24040574
TI  - Frequencies of Functional Polymorphisms in Three Pharmacokinetic Genes of
      Clinical Interest within the Admixed Puerto Rican Population.
AB  - OBJECTIVE: This cross-sectional study was aimed at determining the allele
      frequencies for the CYP2C19*2, CYP2C19*3, CYP2D6*10 and PON1 (rs662)
      polymorphisms in the Puerto Rican population. The CYP2C19, CYP2D6 and PON1 genes
      are known to be associated with functional changes in drug metabolism and
      activation. Individuals carrying the aforementioned polymorphisms are at a higher
      risk of suffering from drug-induced adverse events and/ or unresponsiveness from
      a variety of drugs that includes antidepressants, atypical antipsychotics and
      antiplatelet compounds. Information on the frequency of these polymorphisms is
      more commonly found on homogeneous populations, but is scarce in highly
      heterogeneous populations like Hispanics, as in the case of Puerto Ricans.
      METHOD: Genotyping was carried out in 100 genomic DNA samples from dried blood
      spots supplied by the Puerto Rican Newborn Screening program using Taqman(r)
      Genotyping Assays. RESULTS: The Minor Allele Frequencies (MAF) obtained were 9%
      for CYP2C19*2 and CYP2D6*10, 50% for PON1 (rs662), while the CYP2C19*3 variant
      was not detected in our study. Furthermore, Hardy Weinberg equilibrium analysis
      was assessed as well as a comparison between Puerto Rico and other reference
      populations using a Z-test for proportions. CONCLUSION: The observed allele and
      genotype frequencies on these relevant pharmacogenes in Puerto Ricans were more
      closely related to those early reported in two other reference populations of
      Americans (Mexicans and Colombians).

PMID- 24040575
TI  - Missing Data Methods for Partial Correlations.
AB  - In the dementia area it is often of interest to study relationships among
      regional brain measures; however, it is often necessary to adjust for covariates.
      Partial correlations are frequently used to correlate two variables while
      adjusting for other variables. Complete case analysis is typically the analysis
      of choice for partial correlations with missing data. However, complete case
      analysis will lead to biased and inefficient results when the data are missing at
      random. We have extended the partial correlation coefficient in the presence of
      missing data using the expectation-maximization (EM) algorithm, and compared it
      with a multiple imputation method and complete case analysis using simulation
      studies. The EM approach performed the best of all methods with multiple
      imputation performing almost as well. These methods were illustrated with
      regional imaging data from an Alzheimer's disease study.

PMID- 24040577
TI  - Exploring Maternal and Child Effects of Comorbid Anxiety Disorders among African
      American Mothers with Depression.
AB  - Comorbid depression and anxiety disorders are commonly experienced in mothers.
      Both maternal depression and anxiety as well as their comorbidity has been shown
      to increase psychopathology in children, however, there is limited research
      focusing on African American families. The aim of this study is to examine
      whether comorbid anxiety disorders are associated with maternal depression
      severity, kinship support, and child behavioral problems in a sample of African
      American mothers with depression. African American mothers (n = 77) with a past
      year diagnosis of a depressive disorder and a child between the ages of ages 8-14
      were administered a clinician interview and measures of maternal depression
      severity, kinship support, and child behavior problems (internalizing and
      externalizing) in a cross-sectional design. Results showed that more than half
      (58%) of the mothers had a comorbid anxiety disorder and a third had
      Posttraumatic Stress Disorder (PTSD). Regression analyses showed that comorbid
      PTSD and Social Phobia were positively associated with maternal depression
      severity. Maternal comorbid Obsessive Compulsive Disorder (OCD) was associated
      with child internalizing symptoms. The findings are consistent with other
      research demonstrating negative outcomes with maternal comorbidity of depression
      and anxiety, however, there is limited research focused on maternal depression
      and OCD or PTSD. The study suggests that it is important to consider comorbid
      anxiety and cultural issues when conceptualizing, studying, and treating mothers
      with depression and their families.

PMID- 24040578
TI  - An Academic-Industry Collaboration to Develop an EHR Module for Primary Care.

PMID- 24040580
TI  - Latino Subgroup as a Moderator of the Relationship between Language Usage and
      Alcohol Use in a National Sample of Latino Emerging Adults.
AB  - Emerging adulthood represents a period of increased risk for alcohol use. For
      Latino emerging adults, less is known regarding the role cultural variables play
      in alcohol use behaviors. Research in this area has primarily been conducted
      using Latino college student samples and/or a single Latino subgroup. This study
      investigates Latino subgroup as a moderator of the relationship between language
      usage and alcohol use variables, using a nationally-representative sample of
      Latino emerging adults from the National Longitudinal Study of Adolescent Health
      (Add Health). Participants (N=2,477) identified as Mexican/ Mexican American,
      Cuban/ Cuban American, Puerto Rican, or Central/South American/Other Hispanic.
      Results of regression analyses indicated that gender, education, and language
      usage have a differential impact on alcohol use and binge drinking behaviors
      among individuals from different Latino subgroups. Implications for future
      research and alcohol prevention are discussed.

PMID- 24040579
TI  - Update on Epidemiology and Treatment of MRSA Infections in Children.
AB  - In 2000-10 the epidemiology of pediatric MRSA infections in the United States was
      transformed with an epidemic of CA-MRSA infections. We review the epidemiology of
      MRSA in the community and in the health care setting, including intensive care
      units, among infants and CF patients, and in households as well as the impact
      that the CA-MRSA epidemic has had on hospitalization with MRSA infections. Risk
      factors for carriage, transmission, and initial and recurrent infection with MRSA
      are discussed. New studies on the treatment of pediatric MRSA infections and on
      the efficacy of MRSA decolonization are reviewed.

PMID- 24040581
TI  - An RCT of an Internet Intervention for Pediatric Encopresis with One Year Follow
      Up.

PMID- 24040582
TI  - Bias problems in culture-independent analysis of environmental bacterial
      communities: a representative study on hydrocarbonoclastic bacteria.
AB  - Culture-dependent methods for bacterial community analysis are currently
      considered obsolete; therefore, molecular techniques are usually used instead.
      The results of the current study on hydrocarbonoclastic bacteria in various oily
      habitats in Kuwait showed however, that the bacterial identities varied
      dramatically according to the analytical approach used. For six desert and six
      seawater samples used in this study, the culture-independent and culture
      dependent techniques each led to a unique bacterial composition. Problems related
      to the culture-dependent technique are well known. The results of the current
      study highlighted bias problems other than those already recorded in the
      literature for the molecular approaches. Thus, for example, in contrast to the
      culture-dependent technique, the primers used in the molecular approach
      preferentially amplified the 16S rDNAs of hydrocarbonoclastic bacteria in total
      genomic DNAs of all the studied environmental samples, and in addition, failed to
      reveal in any environmental sample members of the Actinobacteria. The primers
      used in the molecular approach also amplified certain "pure" 16S rDNAs, but
      failed to do so when these DNAs were in mixture. In view of these results, it is
      recommended that the two analytical approaches should be used simultaneously
      because their combined results would reflect the bacterial community composition
      more precisely than either of them can do alone. 

PMID- 24040583
TI  - Image-guided therapy system for interstitial gynecologic brachytherapy in a
      multimodality operating suite.
AB  - In this contribution, an image-guided therapy system supporting gynecologic
      radiation therapy is introduced. The overall workflow of the presented system
      starts with the arrival of the patient and ends with follow-up examinations by
      imaging and a superimposed visualization of the modeled device from a PACS
      system. Thereby, the system covers all treatments stages (pre-, intra- and
      postoperative) and has been designed and constructed by a computer scientist with
      feedback from an interdisciplinary team of physicians and engineers. This
      integrated medical system enables dispatch of diagnostic images directly after
      acquisition to a processing workstation that has an on-board 3D Computer Aided
      Design model of a medical device. Thus, allowing precise identification of
      catheter location in the 3D imaging model which later provides rapid feedback to
      the clinician regarding device location. Moreover, the system enables the ability
      to perform patient-specific pre-implant evaluation by assessing the placement of
      interstitial needles prior to an intervention via virtual template matching with
      a diagnostic scan. 

PMID- 24040584
TI  - Eleven secondary cancers after hematopoietic stem cell transplantation using a
      total body irradiation-based regimen in 370 consecutive pediatric and adult
      patients.
AB  - About the bone marrow transplantation that high dose chemotherapy and total-body
      irradiation (TBI) are used for as conditioning regimen, a late toxicity may
      become the problem in the long-term survival patient. One of the toxicities which
      has been implied to be associated with TBI is secondary cacinogenesis. Between
      June 1995 and December 2010, 370 patients who were undergoing allogeneic
      hematopoietic stem cell transplantation using a TBI-based regimen at our
      department, were the subjects of this study. Eleven secondary cancers occurred in
      10 patients. The median time from transplantation to diagnosis of a secondary
      cancer was 6.8 years. In this analysis, the cumulative incidence rate of
      secondary cancer at 5 and 10 years was 2.15% and 6.46%, respectively after TBI in
      our institution. 

PMID- 24040585
TI  - Combination of extracts from Aristolochia cymbifera with streptomycin as a
      potential antibacterial drug.
AB  - The appearance of new antibiotic-resistant bacteria is a societal problem that
      requires the development of new alternative treatments. Therefore, this work
      evaluated the antibacterial activity of ethanolic (EHI), dichloromethanic (EDI)
      and hexanic (EHE) extracts from Aristolochia cymbifera stems and the combination
      of these extracts with an antimicrobial drug to develop a new antibacterial
      therapy. The EDI, EHE and EHI extracts were obtained by maceration using three
      different solvents. The minimal inhibitory concentrations (MIC) of these extracts
      were determined using the microdilution test to determine the antibacterial
      potential of these extracts and their combination with streptomycin against
      Staphylococcus aureus, Bacillus cereus, Klebsiella pneumoniae and Shigella
      flexneri. The extract dose leading to the cytotoxicity of 50% of the cells (CC50)
      was evaluated using mammalian cells MA104 and the 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. The extracts had a MIC
      under 500 mg/L and a CC50 lower than 50 mg/L. The antibiotic/extract proportion
      influenced the antibacterial activity of the mixtures, and the proportion that
      optimized the antibacterial activity of streptomycin was a mixture that contained
      75 percent of extract. This composition included less than 6.5 mg/L of extract
      and 2.5 mg/L of streptomycin and has potential as a new antibacterial therapy. 

PMID- 24040586
TI  - Estimation of length-weight relationship and condition factor of spotted
      snakehead Channa punctata (Bloch) under different feeding regimes.
AB  - Comparative study was conducted to observe the efficacy of different feeding
      regimes on growth of Channa punctata. Six iso- proteinous diets were prepared by
      using different agro industrial by-products. Maximum weight gain was recorded
      with diet having 66.75% rice bran, 11.50% mustard cake, 23.0% groundnut cake, 5%
      molasses, 1.5% vitamin-mineral mixture and 0.5% salt with specific growth rate of
      0.408. The experimental fish recorded the value of exponent 'b' in the range of
      2.7675 to 4.3922. The condition factor 'K' of all experimental fish was above 1.0
      (1.094- 1.235) indicating robustness or well being of experimented fish. 

PMID- 24040587
TI  - Pediatric Secondhand Smoke Exposure: Moving Toward Systematic Multi-Level
      Strategies to Improve Health.

PMID- 24040588
TI  - Neonatal neuroblastoma with inferior vena cava syndrome.
AB  - Neuroblastoma (NBL) is a neuroectodermal tumor derived from neural crest cells.
      The biological and clinical behavior of NB is extremely heterogenous. We here
      report a newborn who presented as 4S NBL with a massive hepatomegaly resulting in
      IVC syndrome. 

PMID- 24040589
TI  - Transection of gut loop due to post-operative adhesions.
AB  - Transection of gut due to adhesive band is an unusual complication of adhesive
      bowel disease. A 2-year old female presented with signs and symptoms of
      intestinal obstruction. Eight months earlier she underwent laparotomy for
      excision of duplication cyst of ileum. Exploratory laparotomy performed during
      current admission showed complete transection of gut. 

PMID- 24040590
TI  - Congenital laryngeal cyst: a rare cause of polyhydramnios.
AB  - Congenital laryngeal cyst is a rare cause of airway obstruction that may require
      urgent diagnosis and treatment. We report a case of a neonate having history of
      polyhydramnios and severe respiratory distress at birth. A laryngeal cyst
      detected during intubation. The outcome of laryngoscopic treatment of the cyst
      was favorable. 

PMID- 24040591
TI  - Mature cystic teratoma of liver.
AB  - A four-year-old boy presented with constipation and mild abdominal distention for
      one year. Radiologic investigations showed a multiloculated cystic lesion in the
      caudate lobe of liver with focal calcification in the wall. The child underwent
      laparotomy with marsupialization of the cystic lesion. Histopathologic
      examination showed mature teratoma of liver. 

PMID- 24040592
TI  - Giant Hydatid Cyst within a Congenital Cystic Adenomatoid Malformation of the
      Lung.
AB  - A case of hydatid cyst within a congenital cystic adenomatoid malformation (CCAM)
      of the right lower lobe of lung in an 8-year-old girl is reported. Presence of
      CCAM was confirmed on histopathology of the lung tissue attached to the specimen.

PMID- 24040593
TI  - Maffucci's Syndrome or a Variant?
AB  - Maffucci's syndrome is a rare non hereditary disorder characterized by multiple
      enchondromas and haemangiomas. A 12 year old boy presented with a painful
      swelling at his right hand and deformed left upper limb. On detailed workup, he
      was found to have multiple enchondromas involving long bones and a single
      haemangioma. A diagnosis of Maffucci's syndrome was established. The clinical
      features and workup of the disease in our patient is reported. 

PMID- 24040594
TI  - Prostatic utricle cyst: a clinical dilemma.
AB  - Prostatic utricle cyst is a rare midline cystic lesion between the urinary
      bladder and the rectum, commonly associated with hypospadias. Along with its
      rarity, it presents a challenge in its diagnosis and proper management. We report
      a case of large prostatic utricle cyst that was managed conservatively. 

PMID- 24040595
TI  - VURD Syndrome: Report of Three Cases.
AB  - Hoover and Duckett identified the relationship between valves, reflux, and
      dysplasia, commonly known as VURD (Posterior urethral valve, Unilateral
      vesicoureteral reflux, Renal dysplasia) syndrome. They noted preserved
      contralateral renal function in patients with unilateral reflux into a non
      refluxing kidney. The proposed mechanism of this protection is that the refluxing
      collecting system acts as a pressure pop-off. Here we report three cases of VURD
      syndrome. 

PMID- 24040596
TI  - Infected mature teratoma of mesentery in a child.
AB  - Mesenteric teratomas are extremely rare in children. We report a case of 5-year
      old girl with abdominal mass and fever. At operation, a multicystic mass with
      variable consistency found within the leaves of the mesentery of jejunum with pus
      in it. Histopathology examination showed mature infected teratoma of the
      mesentery. 

PMID- 24040597
TI  - Colonic gastrointestinal stromal tumour presenting as intussusception.
AB  - Gastrointestinal stromal tumours (GIST) are rare in paediatric patients and have
      a discrete clinicopathological and molecular divergence from that observed in
      adults. In the present report we present a case of a 2-month-old female in whom
      colonic gastrointestinal stromal tumour acted as a lead point of colocolic
      intussusception. Laparoscopically assisted reduction of the intussusception and
      resection of tumour was done. 

PMID- 24040598
TI  - Suprascapular lipoblastoma extending in to the thorax.
AB  - Lipoblastoma is a rare benign soft-tissue neoplasm that occurs most commonly in
      children less than 3 year of age. We present a case of left suprascapular
      lipoblastoma in an 11-month-old boy which grew into the thorax and was approached
      by thoracoscopy. In this case thoracoscopic approach was the best option to reach
      the intrathoracic component of the mass in the apex of the left side of the
      chest. 

PMID- 24040599
TI  - Perforated neonatal appendicitis with pneumoperitoneum.
AB  - Acute appendicitis is a rare condition in neonates, with a high mortality. If
      perforated, it seldom presents with radiologically significant pneumoperitoneum.
      An 11-day-old newborn presented with abdominal distension and reluctance to
      feeds. X-ray abdomen revealed significant pneumoperitoneum. After optimization of
      his condition, exploratory laparotomy was performed. Perforated appendix was
      found and appendicectomy done. Post operative course was stormy that lead to
      demise of the baby. 

PMID- 24040600
TI  - Single trocar transanal endoscopy in a child.
AB  - Single trocar transanal endoscopic surgery (STTE) is a well-known technique for
      evaluation and management of rectal lesions in adults. We used an 11mm balloon
      trocar with a 10mm operative optic, introduced into the anal canal to excise a
      rectal lesion along with multiple rectal biopsies in a child. Rectal visibility
      was good with an ease to maintain the rectum insufflated. 

PMID- 24040601
TI  - Delayed diagnosis of infected posterior mediastinal teratoma.
AB  - Mediastinal teratomas are rarely reported in children. We report a 12-year-old
      child, diagnosed and treated as empyema thoracis in a peripheral setting for 18
      months. In our centre, CT scan performed revealed a well circumscribed
      multiloculated cystic lesion containing fat, bone and teeth, suggestive of a
      teratoma. The mass was excised and found to be an infected posterior mediastinal
      teratoma, confirmed on histopathology. 

PMID- 24040602
TI  - A case of van wyk-grumbach syndrome.

PMID- 24040603
TI  - Atypical leydig cell tumor in a young child.

PMID- 24040604
TI  - Is linear wound closure acceptable option for congenital midline cervical cleft
      excision in neonates?

PMID- 24040605
TI  - Langerhans cell histiocytosis mimicking osteomyelitis in an infant.

PMID- 24040606
TI  - Polyorchidism: a rare finding in inguinal swelling.

PMID- 24040607
TI  - Congenital anterior urethral diverticulum presenting with fluctuant penile mass.

PMID- 24040608
TI  - Lymphangioma presenting as juxta-articular swelling in children: a case series.

PMID- 24040609
TI  - Isolated renal echinococcosis with hydatiduria in a girl.

PMID- 24040610
TI  - A Prolapsing Vitello-intestinal Duct in Newborn.

PMID- 24040611
TI  - Stump appendicitis seven years after appendectomy.

PMID- 24040612
TI  - Colorful lighting in the operating room.

PMID- 24040613
TI  - Where do we stand on the relationship between tau biomarkers and mild cognitive
      impairment?
AB  - We present an editorial on a recent publication by Amlien et al. [2013] in which
      diffusion tensor imaging (DTI) was used to quantify longitudinal decreases in
      fractional anisotropy (FA) and increased radial diffusivity (DR) in patients with
      mild cognitive impairment (MCI). These longitudinal alterations were found to be
      greater in MCI patients with high cerebrospinal fluid (CSF) tau levels at
      baseline and greater than healthy controls. Amlien et al. concluded that tau
      levels were an important early biomarker for predicting rate of disease
      progression and outcome. The results of this study are an interesting finding for
      possible predictive use of tau levels in MCI. However, in our assessment, the
      methodology does not support the conclusion that CSF total tau levels are
      predictive of MCI progression towards a disease state such as Alzheimer's disease
      (AD). Further longitudinal study is needed, that includes follow-up
      neuropsychological assessment and conversion of subjects in the study to AD, to
      conclude that CSF total tau levels represent a predictive biomarker of MCI
      progression towards AD. 

PMID- 24040614
TI  - MR quantitative biomarkers of non-alcoholic fatty liver disease: technical
      evolutions and future trends.
AB  - Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis
      as the earliest manifestation and hallmark, and ranges from benign fatty liver to
      non-alcoholic steatohepatitis (NASH). Liver biopsy (LB) is considered the
      reference standard for NAFLD diagnosis, grading and characterization, but it is
      limited by its invasiveness and observer-dependence. Among imaging surrogates for
      the assessment of hepatic steatosis, MR is the most accurate. (1)H MR
      spectroscopy (MRS) provides a quantitative biomarker of liver fat content (LFC)
      called proton density fat fraction (PDFF), but it is time-consuming, not widely
      available and limited in sample size. Several MR imaging (MRI) techniques, in
      particular fat suppression and in-opposed phase techniques, have been used to
      quantify hepatic steatosis, mainly estimating LFC from water and fat signal
      intensities rather than proton densities. Several technical measures have been
      introduced to minimize the effect of confounding factors, in particular a low
      flip angle, a multiecho acquisition and a spectral modeling of fat with multipeak
      reconstruction to address respectively T1 effect, T2* effect, and the
      multifrequency interference effects of fat protons, allowing to use MRI to
      estimate LFC based on PDFF. Tang et al. evaluated MRI-estimated PDFF, obtained by
      applying the above-mentioned technical improvements, in the assessment of hepatic
      steatosis, using histopathology as the reference standard. The identification of
      PDFF thresholds, even though to be further explored and validated in larger and
      more diverse cohorts, is useful to identify steatosis categories based on MRI
      based steatosis percentages. MRI, with the new refined techniques which provide a
      robust quantitative biomarker of hepatic steatosis (PDFF) evaluated on the whole
      liver parenchyma, is a promising non-invasive alternative to LB as the gold
      standard for steatosis diagnosis and quantification. 

PMID- 24040615
TI  - C-arm dual-phase cone-beam CT: a revolutionary real-time imaging modality to
      assess drug-eluting beads TACE success in liver cancer patients.
AB  - The advent of cone-beam computed tomography (CBCT) in the angiography suite has
      been revolutionary in interventional radiology. CBCT offers 3 dimensions (3D)
      diagnostic imaging in the interventional suite and can enhance minimally-invasive
      therapy beyond the limitations of 2D angiography alone. The role of CBCT has been
      recognized in transcatheter arterial chemoembolization (TACE) treatment of liver
      cancer especially with the recent introduction of dual-phase CBCT (DP-CBCT) for
      unresectable hepatocellular carcinoma (HCC) treatment. Loffroy and colleagues
      proposed the use of intraprocedural C-arm DP-CBCT immediately after TACE with
      doxorubicin-eluting beads to predict HCC tumor response at 1-month magnetic
      resonance (MR) imaging follow-up. They reported a significant relationship
      between tumor enhancement seen at DP-CBCT after TACE and objective MR imaging
      response at 1-month follow-up, suggesting that DP-CBCT can be used to predict
      tumor response after TACE. If confirmed in larger studies, this imaging modality
      may play a key role in the improvement of treatment planning, especially with
      regard to the need for repeat treatment. More important, a potential clinical
      implication of using intraprocedural DP-CBCT in these patients might be
      elimination of 1-month follow-up MR imaging. 

PMID- 24040616
TI  - Automatic functional analysis of left ventricle in cardiac cine MRI.
AB  - RATIONALE AND OBJECTIVES: A fully automated left ventricle segmentation method
      for the functional analysis of cine short axis (SAX) magnetic resonance (MR)
      images was developed, and its performance evaluated with 133 studies of subjects
      with diverse pathology: ischemic heart failure (n=34), non-ischemic heart failure
      (n=30), hypertrophy (n=32), and healthy (n=37). MATERIALS AND METHODS: The
      proposed automatic method locates the left ventricle (LV), then for each image
      detects the contours of the endocardium, epicardium, papillary muscles and
      trabeculations. Manually and automatically determined contours and functional
      parameters were compared quantitatively. RESULTS: There was no significant
      difference between automatically and manually determined end systolic volume
      (ESV), end diastolic volume (EDV), ejection fraction (EF) and left ventricular
      mass (LVM) for each of the four groups (paired sample t-test, alpha=0.05). The
      automatically determined functional parameters showed high correlations with
      those derived from manual contours, and the Bland-Altman analysis biases were
      small (1.51 mL, 1.69 mL, -0.02%, -0.66 g for ESV, EDV, EF and LVM, respectively).
      CONCLUSIONS: The proposed technique automatically and rapidly detects
      endocardial, epicardial, papillary muscles' and trabeculations' contours
      providing accurate and reproducible quantitative MRI parameters, including LV
      mass and EF.

PMID- 24040617
TI  - Utility of ADC measurement on diffusion-weighted MRI in differentiation of
      prostate cancer, normal prostate and prostatitis.
AB  - To determine the utility of apparent diffusion coefficient (ADC) values in
      differentiation of prostate cancer from normal prostate parenchyma and
      prostatitis we obtained ADC values of 50 patients at b 100, 600 and 1,000 s/mm(2)
      diffusion gradients. The ADC values of prostate cancer group were significantly
      lower than normal prostate and prostatitis group at b 600 and 1,000 s/mm(2)
      gradients. The ADC values at high diffusion gradients may be used in
      differentiation prostate cancer from normal prostate and prostatitis. 

PMID- 24040619
TI  - A case of lower-neck cystic lymphangioma: correlative US, CT and MR imaging
      findings.

PMID- 24040618
TI  - Image homogenization using pre-emphasis method for high field MRI.
AB  - Radiofrequency (RF) field (B 1) inhomogeneity due to shortened wavelength at high
      field is a major cause of magnetic resonance imaging (MRI) nonuniformity in high
      dielectric biological samples (e.g., human body). In this work, we propose a
      method to improve the B 1 and MRI homogeneity by using pre-emphasized non-uniform
      B 1 distribution. The intrinsic B 1 distribution that could be generated by a RF
      volume coil, specifically a microstrip transmission line (MTL) coil used in this
      work, was pre-emphasized in the sample's periphery region of interest to
      compensate for the central brightness induced by high frequency interference
      effect due to shortened wave length. This pre-emphasized non-uniform B 1 can be
      realized by varying the parameters of microstrip elements, such as the substrate
      thickness of MTL volume coil. Both numerical simulation and phantom MR imaging
      studies were carried out to investigate the feasibility and merit of the proposed
      method in achieving homogeneous MR images. The simulation results demonstrate
      that by using a pre-emphasized B 1 distribution generated by the MTL volume coil,
      relatively uniform B 1 distribution and homogeneous MR image (98% homogeneity)
      within the spherical phantom (15 cm diameter) were achieved with 4.5 mm
      thickness. The B 1 and MRI intensity distributions of a 16-element MTL volume
      coil with fixed substrate thickness and five varied saline loads were modeled and
      experimentally tested. Similar results from both simulation and experiments were
      obtained, suggesting substantial improvements of B 1 and MRI homogeneities within
      the phantom containing 125 mM saline. The overall results demonstrate an
      efficient B 1 shimming approach for improving high field MRI. 

PMID- 24040620
TI  - An abdominal desmoid-type fibromatosis.

PMID- 24040621
TI  - Progranulin: a novel regulator of gastrointestinal cancer progression.
AB  - Progranulin (PGRN) is a soluble factor that regulates cell proliferation,
      motility and inflammation. A role for PGRN in the progression of ovarian and
      breast cancers is well established. However, the expression and subsequent
      consequences of PGRN on the progression of gastrointestinal tumors is not well
      recognized. This review briefly summarizes our current knowledge of the
      mechanisms of action of PGRN and highlights the role of this signaling molecule
      in various gastrointestinal cancers.

PMID- 24040622
TI  - A Novel ERAP2 Haplotype Structure in a Chilean Population: Implications for ERAP2
      Protein Expression and Preeclampsia Risk.
AB  - Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum
      aminopeptidase 2 (ERAP2) gene are associated with preeclampsia (PE) in different
      populations. rs2549782, a coding variant (N392K) that significantly affects
      substrate specificity, is in linkage disequilibrium (LD) with rs2248374, a marker
      SNP associated with ERAP2 protein expression in previously studied populations.
      As a result of non-sense mediated RNA decay, ERAP2 protein is not expressed from
      the rs2248374 G allele. We previously reported that the fetal rs2549782 minor G
      allele is associated with PE in African-Americans, but not Chileans. In this
      study, we found that rs2549782 was in LD with rs2248374 in African-Americans, but
      not in Chileans. The unexpected lack of strong LD in Chileans raised the
      possibility that rs2248374 could be associated with PE in the absence of an
      association with rs2549782. However, we found no significant association for this
      allele with PE in Chileans. Chileans homozygous for the rs2248374 G allele did
      not express 110 kDa ERAP2 protein, consistent with non-sense mediated RNA decay,
      and carriers of the rs2248374 A allele did. We conclude that the Chilean ERAP2
      haplotype structure allows for the expression of the major T allele of rs2549782
      encoding 392N, which could impact peptide trimming and antigen presentation. Our
      discovery of racial differences in genetic structure and association with PE
      reveal here-to-fore unrecognized complexity of the ERAP2 locus.

PMID- 24040623
TI  - Twin Mitochondrial Sequence Analysis.
AB  - When applying genome-wide sequencing technologies to disease investigation, it is
      increasingly important to resolve sequence variation in regions of the genome
      that may have homologous sequences. The human mitochondrial genome challenges
      interpretation given the potential for heteroplasmy, somatic variation, and
      homologous nuclear mitochondrial sequences (numts). Identical twins share the
      same mitochondrial DNA (mtDNA) from early life, but whether the mitochondrial
      sequence remains similar is unclear. We compared an adult monozygotic twin pair
      using high throughput-sequencing and evaluated variants with primer extension and
      mitochondrial pre-enrichment. Thirty-seven variants were shared between the twin
      individuals, and the variants were verified on the original genomic DNA. These
      studies support highly identical genetic sequence in this case. Certain low-level
      variant calls were of high quality and homology to the mitochondrial DNA, and
      they were further evaluated. When we assessed calls in pre-enriched mitochondrial
      DNA templates, we found that these may represent numts, which can be
      differentiated from mtDNA variation. We conclude that twin identity extends to
      mitochondrial DNA, and it is critical to differentiate between numts and mtDNA in
      genome sequencing, particularly since significant heteroplasmy could influence
      genome interpretation. Further studies on mtDNA and numts will aid in
      understanding how variation occurs and persists.

PMID- 24040624
TI  - Pediatric Mechanical Support with an External Cardiac Compression Device.
AB  - The PediBooster external cardiac compression device is a minimally invasive, non
      blood contacting Biventricular Assist Device (BiVAD) intended for pediatric use.
      It is being developed as a palliative therapy for acute Postcardiotomy Shock
      (PCS). The PediBooster extracardiac wrap is pneumatically actuated to
      circumferentially compress the heart, providing co-pulsation support. Attachment
      is via a novel hydrogel coating. Early versions of the wrap were tested in vivo
      using a single ventricle congenital heart disease model with postcardiotomy
      shock, which proved unstable and demonstrated high peri-operative mortality. The
      final wrap design was tested in 4 acute studies with piglets (5.1 +/- 0.3 kg),
      where the combination of ASD and PA banding induced acute right ventricular
      dysfunction. Data collected included routine hemodynamic values, TEE, video of
      the exposed heart, and cardiac histology. The model proved stable for support
      durations ranging from 2 to 16 hours. The wrap restricted the heart in 3 of the 4
      animals, as evidenced by increased diastolic LVP during support compared to the
      baseline failure condition. TEE and video data showed good attachment and
      function of the wrap, particularly during the final 16 hr study. This model of
      congenital heart disease shows promise for chronic (24-72 hr) studies.
      Ventricular filling during support may be improved by adjusting wrap dimensions
      to eliminate end diastolic restriction.

PMID- 24040625
TI  - Autoimmune Pancreatitis.
AB  - Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory
      disorder of the pancreas. It has gained increasing recognition due to a
      presentation that can mimic difficult to treat disorders such as pancreatic
      cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast,
      autoimmune pancreatitis is a benign disease that is very responsive to therapy
      with corticosteroids. There are two types of AIP. Type 1 disease is the most
      common worldwide and is associated with extrapancreatic manifestations and
      elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity
      of IgG4-positive cells, and is more difficult to diagnose. This review provides
      an update on the diagnosis, pathophysiology and treatment of AIP, with special
      emphasis on the two subtypes.

PMID- 24040626
TI  - Estimation of cytogenetic risk among coke oven workers exposed to polycyclic
      aromatic hydrocarbons.
AB  - Polycyclic aromatic hydrocarbons (PAHs) result from the incomplete combustion of
      natural or synthetic organic materials. The working environment at a coke plant
      can negatively affect the employed workers who were exposed to coke oven
      emissions containing PAHs, which formed and released into the environment by the
      process of pyrolysis of coke. This study aims to analyze the relationship between
      the exposure of PAHs and the risk of genetic damages such as chromosomal
      alteration (CA), micronucleus (MN), and DNA damage (PCR-RFLP) in peripheral blood
      lymphocytes of 27 coke oven workers and equal number of control subjects. The
      exposed subjects and controls were divided into two groups based on their age
      (group I<35 years and group II >=35 years). The exposed subjects were further
      classified into two groups based on the exposure period (<12 years and >=12
      years). The frequencies of CA and MN in exposed subjects are relatively high with
      respect to controls. The XRCC1 399 Arg/gln polymorphism showed a substantial
      smaller difference in allele frequencies between exposed and control subjects.
      Based on present data, it was concluded that coke oven workers under risk should
      be monitored for adverse effects of the any long-term exposure.

PMID- 24040627
TI  - Production of oleanolic acid glycosides by hairy root established cultures of
      Calendula officinalis L.
AB  - In order to initiate hairy root culture initiation cotyledons and hypocotyls of
      Calendula officinalis L. were infected with Agrobacterium rhizogenes strain ATCC
      15834 or the same strain containing pCAMBIA 1381Z vector with beta-glucuronidase
      reporter gene under control of promoter of NIK (Nematode Induced Kinase) gene.
      The efficiency of induction of hairy roots reached 33.8% for cotyledons and 66.6%
      for hypocotyls together for both transformation experiments. Finally, eight
      control and nine modified lines were established as a long-term culture. The
      hairy root cultures showed the ability to synthesize oleanolic acid mainly (97%)
      as glycosides; control lines contained it at the average 8.42 mg . g(-1) dry
      weight in tissue and 0.23 mg . dm(-3) in medium; modified lines: 4.59 mg . g(-1)
      for the tissue, and 0.48 mg . dm(-3) for the medium. Additionally lines showed
      high positive correlation between dry/fresh weight and oleanolic acid
      concentration in tissue. Using the Killiani mixture in acidic hydrolysis of
      oleanolic acid glycosides released free aglycones that were partially acetylated
      in such conditions.

PMID- 24040628
TI  - Detection and differentiation of Newcastle disease virus and influenza virus by
      using duplex real-time PCR.
AB  - Newcastle disease virus (NDV), member of the Paramyxoviridae family and avian
      influenza virus (AIV), member of the Orthomyxoviridae family, are two main avian
      pathogens causing serious economic problems in poultry health. Both are
      enveloped, single-stranded, negative-sense RNA viruses and cause similar
      symptoms, ranging from sub-clinical infections to severe diseases, including
      decrease in egg production, acute respiratory syndrome, and high mortality.
      Similar symptoms hinder the differentiation of infection with the two viruses by
      standard veterinary procedures like clinical examination or necropsy. To overcome
      this problem, we have developed a new duplex real-time PCR assay for the
      detection and differentiation of these two viruses. Eighteen NDV strains,
      fourteen AIV strains, and twelve other (negative control) strains viruses were
      isolated from allantoic fluids of specific pathogen-free (SPF), embryonated eggs.
      Four-weeks-old SPF chickens were co-infected with both viruses (NDV - LaSota and
      AIV - H7N1). Swabs from cloaca and trachea were collected and examined. The
      results obtained in this study show that by using duplex real-time PCR, it was
      possible to detect and distinguish both viruses within less than three hours and
      with high sensitivity, even in case a bird was co-infected. Additionally, the
      results show the applicability of the real-time PCR assay in laboratory practice
      for the identification and differentiation of Newcastle disease and influenza A
      viruses in birds.

PMID- 24040629
TI  - Improving access in gastroenterology: the single point of entry model for
      referrals.
AB  - In 2005, a group of academic gastroenterologists in Calgary (Alberta) adopted a
      centralized referral intake system known as central triage. This system provided
      a single point of entry model (SEM) for referrals rather than the traditional
      system of individual practitioners managing their own referrals and queues. The
      goal of central triage was to improve wait times and referral management. In
      2008, a similar system was developed in Edmonton at the University of Alberta
      Hospital (Edmonton, Alberta). SEMs have subsequently been adopted by numerous
      subspecialties throughout Alberta. There are many benefits of SEMs including
      improved access and reduced wait times. Understanding and measuring complex
      patient flow systems is key to improving access, and centralized intake systems
      provide an opportunity to better understand total demand and system bottlenecks.
      This knowledge is particularly important for specialties such as gastroenterology
      (GI), in which demand exceeds supply. While it is anticipated that SEMs will
      reduce wait times for GI care in Canada, the lack of sufficient resources to meet
      the demand for GI care necessitates additional strategies. 

PMID- 24040630
TI  - Hepatitis C as a prognostic indicator among noncirrhotic patients hospitalized
      with alcoholic hepatitis.
AB  - OBJECTIVE: A nationwide analysis of alcoholic hepatitis (AH) admissions was
      conducted to determine the impact of hepatitis C virus (HCV) infection on short
      term survival and hospital resource utilization. METHODS: Using the Nationwide
      Inpatient Sample, noncirrhotic patients admitted with AH throughout the United
      States between 1998 and 2006 were identified with diagnostic codes from the
      International Classification of Diseases, Ninth Revision. The in-hospital
      mortality rate (primary end point) of AH patients with and without co-existent
      HCV infection was determined. Hospital resource utilization was assessed as a
      secondary end point through linear regression analysis. RESULTS: From 1998 to
      2006, there were 112,351 admissions for AH. In-hospital mortality was higher
      among patients with coexistent HCV infection (41.1% versus 3.2%; P=0.07). The
      adjusted odds of in-hospital mortality in the presence of HCV was 1.48 (95% CI
      1.10 to 1.98). Noncirrhotic patients with AH and HCV also had longer length of
      stay (5.8 days versus 5.3 days; P<0.007) as well as greater hospital charges
      (US$25,990 versus US$21,030; P=0.0002). CONCLUSIONS: Among noncirrhotic patients
      admitted with AH, HCV infection was associated with higher in-hospital mortality
      and resource utilization.

PMID- 24040631
TI  - Liver transplantation for alcoholic liver disease among Canadian transplant
      centres: a national study.
AB  - BACKGROUND/ OBJECTIVE: Alcoholic liver disease (ALD) is a controversial yet
      established indication for liver transplantation (LT), and there is emerging
      evidence supporting a survival benefit in selected patients with severe acute
      alcoholic hepatitis. The aim of the present survey was to describe policies among
      Canadian transplant centres for patients with ALD. METHODS: A survey was
      distributed to the medical directors of all seven liver transplant centres in
      Canada. RESULTS: All seven liver transplant programs in Canada participated in
      the survey. Every centre requires patients to have a minimum of six months of
      abstinence from alcohol before listing for LT. Completion of a rehabilitation
      program is only mandatory in one program; the remaining programs do not mandate
      this if patients have demonstrated prolonged abstinence, and sufficient insight
      and social supports. No program considers LT for patients with severe acute
      alcoholic hepatitis, although six of the seven programs are interested in
      exploring a national policy. Random alcohol checks for waitlisted patients are
      performed routinely on patients listed for ALD at only one centre; the remaining
      centres only perform checks if there is clinical suspicion. In the past five
      years, the mean (+/- SD) number of patients per centre with graft dysfunction
      from recidivism was 10+/-4.36; a mean of 2.5+/-4.36 patients per centre developed
      graft failure. CONCLUSIONS: With minor exceptions, LT policies for subjects with
      ALD are uniform across Canadian transplant programs. Presently, no centres
      perform LT for acute alcoholic hepatitis, although there is broad interest in
      exploring a national policy. Recidivism resulting in graft loss is a rare
      phenomenon.

PMID- 24040632
TI  - Do we eradicate Helicobacter pylori in hospitalized patients with peptic ulcer
      disease?
AB  - BACKGROUND: Helicobacter pylori infection is the most common chronic infection in
      humans. It is a major contributor to the cause of duodenal and gastric ulcers
      worldwide. Its eradication has been shown to reduce rates of H pylori-related
      ulcers as well as other complications such as gastric cancer. OBJECTIVE: To
      determine the rate of appropriate treatment in patients following a diagnosis of
      H pylori infection on biopsy during esophagoduodenoscopy for upper
      gastrointestinal bleeding over a four-year period at a tertiary centre in
      Vancouver, British Columbia. Also evaluated was the rate of eradication
      confirmation using the urea breath test. METHODS: A retrospective review of 1501
      inpatients who underwent esophagoduodenoscopy for upper gastrointestinal bleeding
      (January 2006 to December 2010) was undertaken. Patients who were biopsy stain
      positive for H pylori were selected for drug review either via a provincial
      database (PharmaNet) or via records from patients' family practitioners. Data
      were also obtained via two provincial laboratories that perform the urea breath
      test to determine the rates of confirmation of eradication. RESULTS: Ninety-eight
      patients had biopsy-proven H pylori. The mean (+/- SD) age was 56.13+/-17.9 years
      and 65 were male. Data were not available for 22 patients; the treatment rate was
      52.6% (40 of 76). Of those treated, 12 patients underwent a post-treatment urea
      breath test for eradication confirmation. CONCLUSION: There was substantial
      discrepancy between the number of diagnosed H pylori infections and the rate of
      treatment as well as confirmation of eradication. Numerous approaches could be
      taken to improve treatment and eradication confirmation.

PMID- 24040641
TI  - Stimulation and release from neurons via a dual capillary collection device
      interfaced to mass spectrometry.
AB  - Neuropeptides are cell to cell signaling molecules that modulate a wide range of
      physiological processes. Neuropeptide release has been studied in sample sizes
      ranging from single cells and neuronal clusters, to defined brain nuclei and
      large brain regions. We have developed and optimized cell stimulation and
      collection approaches for the efficient measurement of neuropeptide release from
      neuronal samples using a dual capillary system. The defining feature is a
      capillary that contains octadecyl-modified silica nanoparticles on its inner wall
      to capture and extract releasates. This collection capillary is inserted into
      another capillary used to deliver solutions that chemically stimulate the cells,
      with solution flowing up the inner capillary to facilitate peptide collection.
      The efficiency of peptide collection was evaluated using six peptide standards
      mixed in physiological saline. The extracted peptides eluted from these
      capillaries were characterized via matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF MS) with low femtomole detection
      limits. Using the capillary collection system in small custom-fabricated
      culturing chambers, individual cultured neurons and neuronal clusters from the
      model animal Aplysia californica were stimulated with distinct neuronal
      secretagogues and the releasates were collected and characterized using MALDI-TOF
      MS. 

PMID- 24040642
TI  - Quantification of plaque area and characterization of plaque biochemical
      composition with atherosclerosis progression in ApoE/LDLR(-/-) mice by FT-IR
      imaging.
AB  - In this work the quantitative determination of atherosclerotic lesion area
      (ApoE/LDLR(-/-) mice) by FT-IR imaging is presented and validated by comparison
      with atherosclerotic lesion area determination by classic Oil Red O staining.
      Cluster analysis of FT-IR-based measurements in the 2800-3025 cm(-1) range
      allowed for quantitative analysis of the atherosclerosis plaque area, the results
      of which were highly correlated with those of Oil Red O histological staining
      (R(2) = 0.935). Moreover, a specific class obtained from a second cluster
      analysis of the aortic cross-section samples at different stages of disease
      progression (3, 4 and 6 months old) seemed to represent the macrophages (CD68)
      area within the atherosclerotic plaque. 

PMID- 24040643
TI  - Extruded polymer films pigmented with a heterogeneous ion-pair based lumophore
      for O2 sensing.
AB  - A novel approach to polymeric Ru(II)-diimine luminescent O2 sensors is described.
      The Ru(II)-diimine, tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II)
      dichloride ([Ru(dpp)3](2+)), is first ion-paired to the surface of heterogeneous
      TiO2 particles, rendered negatively charged due to the alkali nature of the
      aqueous solution, to produce an O2 sensitive pigment with a strikingly high
      oxygen sensitivity (i.e. PO2 (S = 1/2) = 0.002 atm, where PO2 (S = 1/2) is
      defined as the amount of oxygen required to reduce the initial, oxygen free
      luminescence by 50%), and a rapid response to oxygen. The pigment is extruded in
      low density polyethylene (LDPE) to produce a thin (60 MUm), flexible, O2 sensing
      plastic film, with an O2 sensitivity (PO2 (S = 1/2) = 0.84 atm) comparable to the
      more traditional homogeneous lumophore ion-pair based O2 sensor ink films
      reported in the literature.

PMID- 24040644
TI  - Novel triazole-based fluorescent probes for Pd2+ in aqueous solutions: design,
      theoretical calculations and imaging.
AB  - The first triazole-containing fluorescent probe with excellent water-solubility
      for Pd(2+) was presented. The results indicated that an amide-triazole-amide
      binding sequence was responsible for the unique affinity of PS-1 toward Pd(2+).
      Among the tested metal ions, only Pd(2+) could selectively quench the
      fluorescence of PS-1 under physiological conditions, while other common
      interference ions like Pt(2+) and Ru(3+) caused little changes. The successful
      fluorescence imaging of Pd(2+) in HeLa cells implied the potential applications
      of PS-1 in biological Pd(2+)-analysis.

PMID- 24040645
TI  - Highly sensitive electrochemical detection of methyl salicylate using
      electroactive gold nanoparticles.
AB  - Electrochemical sensing of methyl salicylate, a key plant volatile has been
      achieved using a gold nanoparticle (AuNP) modified screen printed carbon
      electrode (SPCE). The electrochemical response of planar gold electrodes, SPCE
      and AuNP-SPCE in alkaline electrolyte in the presence and absence of methyl
      salicylate were studied to understand the amperometric response of various
      electrochemical reactions. The reaction mechanism includes hydrolysis of methyl
      salicylate and the oxidation of negative species. The electrochemical responses
      were recorded using cyclic voltammetry and differential pulse voltammetry
      techniques, where the results showed characteristic signals for methyl salicylate
      oxidation. Among the examined electrodes, AuNP-SPCE possessed three fold better
      sensitivity than planar gold and 35 times better sensitivity than SPCE (at 0.5
      V). The methyl salicylate sensing by AuNP-SPCE possessed <5% variation
      coefficient for repeatability, one week of stable performance with no more than
      15% activity loss even if used multiple times (n = 8). Even in the presence of
      high concentration of interfering compounds such as cis-3-hexenol, hexyl acetate
      and cis-hexenyl acetate, AuNP-SPCE retained >95% of its methyl salicylate
      response. The electroanalytical results of soybean extract showed that AuNP-SPCE
      can be employed for the determination of methyl salicylate in real samples. 

PMID- 24040646
TI  - Electrochemical piezoelectric-excited millimeter-sized cantilever (ePEMC) for
      simultaneous dual transduction biosensing.
AB  - A dual mode electrochemical piezoelectric-excited millimeter cantilever (ePEMC)
      sensor is reported for simultaneous in-liquid biochemical sensing. The ePEMC
      incorporates mass-sensing measurement of dynamic-mode cantilevers with
      electrochemical impedance spectroscopy (EIS) commonly employed for transduction
      in sensitive electrochemical biosensors. Such an integrated design allows for
      simultaneous and continuous measurement of resonant frequency shift (Deltaf) and
      charge transfer resistance (RCT) as a target analyte binds to the sensor gold
      surface (0.5 mm(2)) via electromechanical and electrochemical impedance
      spectroscopy, respectively. The properties of ePEMC are demonstrated in three
      experiments: (1) resonant frequency response to electrochemically-deposited metal
      thin-films, (2) resonant frequency response to adsorption of thiolated ssDNA and
      model proteins with subsequent EIS sensing, and (3) simultaneous resonant
      frequency and charge transfer resistance response to model chemisorption of a
      short-chain thiol molecule, mercaptohexanol. Adsorption of all model binding
      analytes caused decrease in sensor resonant frequency and increase in charge
      transfer resistance. Comparison of sensor response to binding of protein and
      thiol molecules showed the two simultaneously transduced signals were
      proportional and showed the same kinetics.

PMID- 24040647
TI  - High specific detection and near-infrared photothermal therapy of lung cancer
      cells with high SERS active aptamer-silver-gold shell-core nanostructures.
AB  - Lung cancer is the leading cause of cancer death worldwide. Its early detection
      is of paramount importance for diagnosis, classification, treatment, and
      improvement of survivorship. However, current methods are not sensitive enough to
      detect lung cancer in its nascent stage. We reported an aptamer-Ag-Au shell-core
      nanostructure-based surface-enhanced Raman scattering (SERS) assay for sensitive
      and specific detection, and near-infrared (NIR) photothermal therapy of lung
      adenocarcinoma cells (A549 cells). The nanostructures target the cells with high
      affinity and specificity via the specific interaction between the aptamer (a 45
      base oligonucleotide) and the cell, and distinguish A549 cells from other types
      of cancer cells (HeLa and MCF-7 cells) and subtypes of lung cancer cells (NCI
      H157, NCI-H520, NCI-H1299, and NCI-H446 cells). The nanostructures have a high
      capability to absorb NIR irradiation and are able to perform photothermal therapy
      of the cells at a very low irradiation power density (0.20 W cm(-2)) without
      destroying the healthy cells and the surrounding normal tissues. In addition, the
      nanostructures exhibit a high SERS activity. Based on the SERS signal of the
      labeled Raman reporter (Rh6G molecules), we can specifically detect A549 cells at
      a very low abundance (~10 cells per mL) and monitor the therapy process of the
      cancer cells. Therefore, this nanostructure-based SERS assay has great potential
      in specific recognition, sensitive detection, and effective photothermal therapy
      of lung cancer.

PMID- 24040648
TI  - Forensic collection of trace chemicals from diverse surfaces with strippable
      coatings.
AB  - Surface sampling for chemical analysis plays a vital role in environmental
      monitoring, industrial hygiene, homeland security and forensics. The standard
      surface sampling tool, a simple cotton gauze pad, is failing to meet the needs of
      the community as analytical techniques become more sensitive and the variety of
      analytes increases. In previous work, we demonstrated the efficacy of non
      destructive, conformal, spray-on strippable coatings for chemical collection from
      simple glass surfaces. Here we expand that work by presenting chemical collection
      at a low spiking level (0.1 g m(-2)) from a diverse array of common surfaces -
      painted metal, engineering plastics, painted wallboard and concrete - using
      strippable coatings. The collection efficiency of the strippable coatings is
      compared to and far exceeds gauze pads. Collection from concrete, a particular
      challenge for wipes like gauze, averaged 73% over eight chemically diverse
      compounds for the strippable coatings whereas gauze averaged 10%. 

PMID- 24040649
TI  - Profiling of diferulates (plant cell wall cross-linkers) using ultrahigh
      performance liquid chromatography-tandem mass spectrometry.
AB  - Recalcitrance of grasses to enzymatic digestion arises to a significant degree
      from a complex array of phenolic crosslinks between cell wall polysaccharide
      chains that inhibit their conversion to biofuels and lower their nutritive value
      for animal feed applications. Polysaccharide esters of ferulic acid are abundant
      in plant cell walls. Crosslinks between polysaccharides are formed through
      oxidative dehydrodimerization of ferulates, producing dehydrodiferulates
      (henceforth termed diferulates). Such ferulates and diferulates further crosslink
      plant cell walls by radical coupling cross-reactions during lignification.
      Although cell wall digestibility can be improved by cell wall metabolic
      engineering, or post-harvest by various pretreatment processes, a more
      comprehensive understanding of the role and impact of ferulate crosslinking on
      polysaccharide hydrolysis would be accelerated by availability of analytical
      methods that can distinguish the various diferulates released during biomass
      pretreatments, many of which are isomers. In this report, we present an ultrahigh
      performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) strategy
      for comprehensive separation and identification of diferulate isomers. Collision
      induced dissociation (CID) mass spectra of [M + H](+) ions distinguished various
      isomers without requiring derivatization. Characteristic product ions for 8-O-4-,
      8-8-non-cyclic, 8-8-cyclic, 8-5-cyclic, 8-5-non-cyclic, and 5-5-linked isomers
      were identified. All diferulates were identified either as di-acids in extracts
      of NaOH-hydrolyzed corn stover, or as a diverse group of diferulate mono- and di
      amides in extracts of Ammonia Fiber Expansion (AFEXTM)-treated corn stover. This
      approach allows for direct analysis of released diferulates with minimal sample
      preparation, and can serve as the foundation for high-throughput profiling and
      correlating pretreatment conditions with biomass digestibility in biorefineries
      producing biofuels and biochemicals. 

PMID- 24040652
TI  - Carboline derivatives with an ortho-linked terphenyl core for high quantum
      efficiency in blue phosphorescent organic light-emitting diodes.
AB  - Two host materials, 9-(3''-(9H-carbazol-9-yl)-[1,1':2',1''-terphenyl]-3-yl)-alpha
      carboline (CzOTCb) and 3,3''-bis(alpha-carbolin-9-yl)-1,1':2',1''-terphenyl
      (CbOTCb), derived from carboline and ortho-linked terphenyl were synthesized as
      high triplet energy materials and showed a high triplet energy of 2.90 eV. CzOTCb
      and CbOTCb were evaluated as the host materials for blue phosphorescent organic
      light-emitting diodes and high quantum efficiencies of 27.4% and 28.8% were
      obtained using the CzOTCb and CbOTCb hosts, respectively.

PMID- 24040651
TI  - Water-soluble non-aggregating zinc phthalocyanine and in vitro studies for
      photodynamic therapy.
AB  - Newly synthesized zinc phthalocyanine bearing sixteen quaternized imidazolyl
      moieties on the periphery displays high water-solubility, lack of aggregation and
      high singlet oxygen quantum yield in water (PhiDelta > 0.33). The in vitro tests
      indicated excellent anticancer photodynamic activity (EC50 = 36.7 nM) and low
      dark toxicity to non-cancerous cells (TC50 = 395 MUM). 

PMID- 24040653
TI  - Calcium carbonate biomineralization utilizing a multifunctional beta-sheet
      peptide template.
AB  - We designed a novel multifunctional beta-sheet peptide template for calcium
      carbonate mineralization. The template self-supplies the mineral source, a
      carbonate ion, by hydrolysis of urea, and regulates the crystal phase and
      morphology of the obtained calcium carbonate. 

PMID- 24040650
TI  - Environmentally responsive MRI contrast agents.
AB  - Biomedical imaging techniques can provide a vast amount of anatomical
      information, enabling diagnosis and the monitoring of disease and treatment
      profile. MRI uniquely offers convenient, non-invasive, high resolution
      tomographic imaging. A considerable amount of effort has been invested, across
      several decades, in the design of non toxic paramagnetic contrast agents capable
      of enhancing positive MRI signal contrast. Recently, focus has shifted towards
      the development of agents capable of specifically reporting on their local
      biochemical environment, where a switch in image contrast is triggered by a
      specific stimulus/biochemical variable. Such an ability would not only strengthen
      diagnosis but also provide unique disease-specific biochemical insight. This
      feature article focuses on recent progress in the development of MRI contrast
      switching with molecular, macromolecular and nanoparticle-based agents. 

PMID- 24040654
TI  - Case reports of PML in patients treated for psoriasis.

PMID- 24040655
TI  - Case reports of PML in patients treated for psoriasis.

PMID- 24040656
TI  - Short implants--a valuable alternative in patients with reduced bone height?

PMID- 24040657
TI  - Reply: To PMID 22094295.

PMID- 24040658
TI  - [Intraoperative inhibition of fibrosis in the modern filtration surgery. Reply].

PMID- 24040659
TI  - [Tribute to Professor Pierre Mauvais-Jarvis, a visionary man 1929-2012].

PMID- 24040660
TI  - [Candidemia and early catheter removal: the debate is far from closed].

PMID- 24040661
TI  - [Vascular replenishment in resuscitation: the end of the hydroxyethyl starches?].

PMID- 24040662
TI  - Reply to S. Girnius et al.

PMID- 24040663
TI  - Reply to P.A. Beatty et al.

PMID- 24040664
TI  - Reply to A.-S. Dieudonne et al and J.M. Rae et al.

PMID- 24040665
TI  - Reply to D.H. Palmer.

PMID- 24040666
TI  - Reply to F. Fiorica et al and D. Vordermark.

PMID- 24040667
TI  - Molecular evolution of myelin basic protein, an abundant structural myelin
      component.
AB  - Rapid nerve conduction in jawed vertebrates is facilitated by the myelination of
      axons, which evolved in ancient cartilaginous fish. We aim to understand the
      coevolution of myelin and the major myelin proteins. We found that myelin basic
      protein (MBP) derived from living cartilaginous fish (sharks and rays) associated
      with the plasma membrane of glial cells similar to the phosphatidylinositol (4,5)
      bisphosphate (PIP2)-binding marker PH-PLCdelta1, and that ionomycin-induced PIP2
      hydrolysis led to its cellular redistribution. We identified two paralogous mbp
      genes in multiple teleost species, consistent with a genome duplication at the
      root of the teleost clade. Zebrafish mbpb is organized in a complex transcription
      unit together with the unrelated gene-of-the-oligodendrocyte-lineage (golli)
      while mbpa does not encode GOLLI. Moreover, the embryonic expression of mbpa and
      mbpb differed, indicating functional specialization after duplication. However,
      both mbpa and mbpb-mRNAs were detected in mature oligodendrocytes and Schwann
      cells, MBPa and MBPb were mass spectrometrically identified in zebrafish myelin,
      both associated with the plasma membrane via PIP2, and the ratio of nonsynonymous
      to synonymous nucleotide-substitution rates (Ka/Ks) was low. Together, this
      indicates selective pressure to conserve many aspects of the cellular expression
      and function of MBP across vertebrate species. We propose that the PIP2-binding
      function of MBP is evolutionarily old and that its emergence in ancient
      gnathostomata provided glial cells with the competence to myelinate.

PMID- 24040668
TI  - Response to Fayaz-Bakhsh and Manesh.

PMID- 24040669
TI  - Response to Fayaz-Bakhsh and Yusefi.

PMID- 24040670
TI  - Possible mechanical roles of glycosaminoglycans in thoracic aortic dissection and
      associations with dysregulated transforming growth factor-beta. Author reply.

PMID- 24040671
TI  - 2013 ESH/ESC guidelines for the management of arterial hypertension.

PMID- 24040672
TI  - Unmet needs in acute cardiovascular care.

PMID- 24040673
TI  - Rubella virus nomenclature update: 2013.

PMID- 24040674
TI  - Health conditions for travellers to Saudi Arabia for the pilgrimage to Mecca
      (Hajj).

PMID- 24040675
TI  - Poliomyelitis outbreak in Somalia and Kenya, 2013.

PMID- 24040676
TI  - Japanese encephalitis: status of surveillance and immunization in Asia and the
      Western Pacific, 2012.

PMID- 24040677
TI  - [Abnormality of auditory ossicle and reconstruction].

PMID- 24040678
TI  - Author's response.

PMID- 24040679
TI  - Response by authors.

PMID- 24040680
TI  - Response by authors.

PMID- 24040681
TI  - Commentary on 'propofol versus thiopental sodium for the treatment of refractory
      status epilepticus-still no answer'.
AB  - This is a commentary on a Cochrane review, published in this issue of EBCH, first
      published as:Prabhakar H, Bindra A, Singh GP, Kalaivani M. Propofol versus
      thiopental sodium for the treatment ofrefractory status epilepticus. Cochrane
      Database of Systematic Reviews 2012, Issue 8. Art. No.: CD009202.DOI:
      10.1002/14651858.CD009202.pub2.

PMID- 24040682
TI  - Extension of expiration dates for two body system listings. Final rule.
AB  - We are extending the expiration dates of the following body systems in the
      Listing of Impairments (listings) in our regulations: Genitourinary Impairments
      and Hematological Disorders. We are making no other revisions to these body
      systems in this final rule. These extensions will ensure that we continue to have
      the criteria we need to evaluate impairments in the affected body systems at step
      three of the sequential evaluation processes for initial claims and continuing
      disability reviews.

PMID- 24040683
TI  - Disease associated with exposure to certain herbicide agents: peripheral
      neuropathy.
AB  - The Department of Veterans Affairs (VA) adopts as a final rule its proposal to
      amend its adjudication regulations by clarifying and expanding the terminology
      regarding presumptive service connection for acute and subacute peripheral
      neuropathy associated with exposure to certain herbicide agents. This amendment
      implements a decision by the Secretary of Veterans Affairs based on findings from
      the National Academy of Sciences (NAS) Institute of Medicine report, Veterans and
      Agent Orange: Update 2010. It also amends VA's regulation governing retroactive
      awards for certain diseases associated with herbicide exposure as required by
      court orders in the class action litigation of Nehmer v. U.S. Department of
      Veterans Affairs.

PMID- 24040684
TI  - Suicide prevention changes focus.

PMID- 24040685
TI  - Tough love for sleepy drivers.

PMID- 24040686
TI  - Uncovering hospital charges: hospitals are reporting their rates for various
      procedures in an effort to satisfy those who want more transparency in health
      care costs.

PMID- 24040687
TI  - Rx for doctor shortage? Expanding nurses' range of duties is one way to address
      our nation's shortage of doctors.

PMID- 24040688
TI  - [Are serum immunoglobulin and tumor marker helpful in differentiating autoimmune
      pancreatitis from pancreatobiliary malignancies?].

PMID- 24040689
TI  - [Heterotopic paragonimiasis presented by intra-abdominal masses].

PMID- 24040691
TI  - Global leprosy: update on the 2012 situation.

PMID- 24040690
TI  - [The efficacy and safety of a tofacitinib in the treatment of active ulcerative
      colitis].

PMID- 24040692
TI  - Monthly report on dracunculiasis cases, January-June 2013.

PMID- 24040693
TI  - [Analysis of Wnt signaling during the morphogenesis of semicircular canal in
      mouse inner ear].

PMID- 24040694
TI  - Identification of 62-kDa protein as an immunogenic antigen of Vibrio vulnificus
      for humans.
AB  - Vibrio vulnificus infection can cause necrotizing fasciitis and sepsis and can
      develop within a few days despite intensive care. The mortality rate is up to 60%
      in vulnerable people. Most patients infected with this microbe have chronic liver
      disease, especially liver cirrhosis or cancer, as an underlying disease. V.
      vulnificus infection is opportunistic, and there is an urgent need to develop an
      anti- V. vulnificus vaccine. Thus, it is important to identify immunogenic
      antigens. We collected human sera from three subject groups: patients with V.
      vulnificus infection, patients with chronic liver disease but without V.
      vulnificus infection, and healthy volunteers with normal liver function.
      Immunoblots of cytosolic and membrane proteins of seven strains of V. vulnificus
      and one of V. parahaemolyticus were performed with sera from these groups.
      Although we could not demonstrate differences in antibody response between the
      groups, all sera showed a strong antibody response to a 62-kDa protein that was
      common to all strains examined. Immunoblots of Escherichia coli and Klebsiella
      pneumoniae also showed strong antibody response to this 62-kDa protein, and the
      possibility of cross-reaction cannot be denied. We identified this 62-kDa protein
      as an immunogenic antigen of V. vulnificus for humans.

PMID- 24040695
TI  - Interpersonal criticism and the clergy.
AB  - Though well-crafted criticism can provide valuable information for the recipient,
      the abundance of literature finds that criticism is overwhelmingly viewed
      negatively. The consequences of adverse interpersonal criticism were assessed by
      a focus group of randomly selected clergy members from a large ministerial
      alliance. Collectively the focus group revealed that interpersonal criticism can
      have deleterious vocational, psychological, and health consequence for those in
      the ministry. Clergy reported that criticism from parishioners, the public,
      denominational officials, and others adversely affect interpersonal relationships
      and can lead to stress, burnout, and early departure from the ministry. The
      participants indicated that current training and resources were inadequate to
      deal with the issue and further denominational support and seminary education was
      necessary.

PMID- 24040696
TI  - Clergy burnout and resilience: a review of the literature.
AB  - In this article, I review the literature on burnout and resilience among clergy.
      The existing research shows that the factors related to clergy burnout include
      the quality of interpersonal skills, relationships outside the congregation,
      establishment of peer/mentor relationships, the existence of high role
      expectations, personal spirituality and the ability to set healthy emotional
      boundaries. Recent studies using positive psychology as a framework identify a
      number of personal and situational qualities that promote resilience in clergy.
      Based on these findings, I suggest interventions that should be made by faith
      groups to better support clergy and make recommendations for further research.

PMID- 24040697
TI  - Take heed, take care!
AB  - This paper offers a synthesis of public and personal narratives about the effects
      of stress in working with "wounded others", weaving together common themes to
      highlight difficulties associated with doing such work. The intention is to
      stimulate conversation among individuals, institutions, and organisations for
      considering ways in which Pastoral Care and Counseling providers can ameliorate
      negative stress-induced effects of their work.

PMID- 24040698
TI  - Teaching research in clinical pastoral education: a survey of model practices.
AB  - The Association of Professional Chaplains (APC) developed Standards of Practice
      for Acute and Long-term settings. Standard 12 promotes research-literate
      chaplains as important for the profession. Since many chaplains receive training
      in clinical pastoral education (CPE) residency programs, the aim of this study
      was to identify model practices for the teaching of research in such programs.
      Using a purposeful sample, this study identified 11 programs that offered
      "consistent and substantive" education in research. Common features included the
      existence of a research champion, a culture supportive of research, and the
      availability of institutional resources. The study identified models and
      methodologies that CPE programs can adopt.

PMID- 24040699
TI  - Translating spiritual care in the chaplain profession.
AB  - Chaplains provide a much-needed service to patients and families requiring
      spiritual care in the healthcare setting. Despite evidence documenting
      improvements quality of life for patients using spiritual services, chaplains
      experience challenges in translating the benefits they provide into concepts
      understood by patients, team members, and administrators. A qualitative study
      using interviews with 19 chaplains found that translation problems occur in three
      main areas: (a) justifying the role to patients and families, (b) determinations
      of what constitutes a "productive" employee, and (c) effective collaboration with
      other members of the health care team. This study outlines several strategies
      used by chaplains to ease the process of translation, as well as some directions
      for future research.

PMID- 24040700
TI  - Hospitalized young adults' expectations of pastoral interventions.
AB  - The objective of this analysis of 4500 inpatients was to identify the experience
      and expectations of 18-35 year olds regarding chaplain visitation and to compare
      results with data from older adults. 71% of young adults reported wanting to be
      visited by a chaplain; 45.5% were visited; 68% indicated that this was important.
      Young adults value chaplains' role as a sign of God's care and presence (77.4%),
      in providing support for family (73.6%), being present during times of anxiety
      (66.0%), and praying/reading scripture with them (62.3%). Results were similar to
      older respondents, but young adults were more likely to value ethical counsel
      from chaplains (58.5% vs. 38.2%). This study provides clinically relevant
      information and suggestions for further research.

PMID- 24040701
TI  - A prayer before I visit.

PMID- 24040702
TI  - "Don't dismiss issues that Francis didn't cover".

PMID- 24040703
TI  - Francis rethinks staffing levels.

PMID- 24040704
TI  - "It's time to improve the safety culture in the health service".

PMID- 24040705
TI  - "The Liverpool Care Pathway is only as good or bad as its user".

PMID- 24040706
TI  - Treating and managing atrial fibrillation.
AB  - The management of atrial fibrillation is complex and is influenced by the type of
      AF, the severity of symptoms, underlying disease and patient choice. The aim of
      treatment is to alleviate symptoms, prevent strokes and reduce other
      complications, such as heart failure. The incidence of AF is increasing due to an
      ageing population and most health professionals will encounter patients with AF
      during their career. A widespread knowledge of AF management among the nursing
      profession is important to ensure that appropriate treatment and patient support
      are provided. This article is the second in a two-part series on AF. Part one
      discussed the importance of detecting and treating AF and screening strategies.
      This second part discusses the management of AF and treatment options, using
      recent guidelines.

PMID- 24040707
TI  - Children discharged against medical advice.
AB  - Discharge against medical advice (DAMA) occurs when a patient leaves a clinical
      setting before the end of treatment and against medical recommendation. The most
      important aspects of DAMA are to ensure ongoing medical needs are met and that it
      is documented meticulously. This article describes a recent retrospective case
      note (audit) study of DAMA in paediatric patients attending a district general
      hospital, followed by a literature review. It also discusses the legal
      implications of DAMA and offers some strategies for clinical practice.

PMID- 24040708
TI  - Pathway to reduce premature death after self-harm.

PMID- 24040709
TI  - 60 seconds with Tony Butterworth.

PMID- 24040710
TI  - Guiding individual jouneys.

PMID- 24040711
TI  - Infectious diseases in Poland in 2011.
AB  - The aim of the study was assessment of the epidemiological situation of
      infectious and parasitic diseases in Poland in 2011 MATERIALS AND METHODS: The
      main source of data to develop the statistical overview was the annual bulletin
      "Infectious diseases in Poland in 2011," and "Vaccinations in Poland in
      2011,"/NIPH-NIH, CSI, 2011 and information contained in the articles of
      epidemiological journal in which authors depth discussion of the epidemiological
      situation of 27 diseases or groups of diseases. Data on deaths are based on the
      statements of the Department of the Central Statistical Office of Demographic
      Studies. RESULTS: Upper respiratory tract infection classified as "influenza and
      influenza-like illness" in 2011, were reported in a total number of 1,156,357
      cases, which was an 108.0% increase of incidence as compared with 2010. and in
      relation to the median of the years 2005 - 2009 of 205.9%. In 2011, food
      infections dominated among the bacterial infections caused by Salmonella, with
      the continuing decline of incidence and fraction of salmonellosis among other
      etiologies. Among the diseases that can be prevented by vaccination it was
      reported 30.7% increase in the incidence of pertussis. In relation to the median
      of the years 2005-2009 is a decrease of 16.9%. A downward trend in the incidence
      of mumps was maintained. As compared to 2010, the incidence decreased by 7.0%.
      When compared to the median of the years 2005 to 2009 the decline was 38.3%. In
      relation to the median of the years 2005-2009 there have been a decrease of the
      number of rubella cases by 67.7% and there have been no reported cases of
      congenital rubella. A further decline in the incidence of invasive disease caused
      by H. influenzae was observed. The incidence of tuberculosis in 2011 increased as
      compared to the previous year from 19.7 to 22/100,000 in respect to all forms of
      tuberculosis, and pulmonary tuberculosis from 18.3 to 20.5/100,000. The number of
      newly diagnosed HIV-infected persons also increased. In 2011 it was reported
      1,105 cases (2.87/100,000), compared with the previous year, an increase of
      14.8%. In 2011, there were reported 221 cases (0.57/100,000) of tick-borne
      encephalitis, i.e. by 25.5% less than in the previous year, the incidence of
      viral meningitis decreased by 11.8%. In 2011, there were no cases of especially
      dangerous infectious diseases: plague, anthrax, diphtheria, polio, rabies and
      viral hemorrhagic fevers besides dengue, of which 5 cases acquired in endemic
      areas were reported to the epidemiological surveillance. Due to infectious and
      parasitic diseases in 2011, died in Poland 3,408 people total. The share of
      deaths from these causes in the total number of deaths was 0.91%, and the
      mortality rate--8.8 per 100,000 population, 52.0% of all deaths were due to
      sepsis.

PMID- 24040712
TI  - Measles in Poland in 2011.
AB  - INTRODUCTION: Since 2001, Poland has been participating in Measles Elimination
      Program coordinated by the World Health Organization (WHO). Commitment in the
      implementation of this program is to maintain 95% of the population vaccinated,
      recording all suspected cases of measles and confirmation of diagnosis in the
      Reference Laboratory. THE PURPOSE OF THE STUDY: To evaluate the epidemiology of
      measles in Poland in 2011, and the degree of implementation of the Measles
      Elimination Program. MATERIAL AND METHODS: The epidemiological situation of
      measles in 2011 was assessed on the basis of the individual reported
      cases/suspected cases of measles, sent to the NIPH-NIH by regional sanitary
      epidemiological stations collected and presented in the newsletter" Infectious
      Diseases and Poisonings in Poland in 2011" and "Vaccinations in Poland in 2011"
      (MP Czarkowski et al, Warsaw 2012, NIZP-PZH, GIS). RESULTS: In 2011, 38 reported
      cases of measles (incidence 0.10/100,000), of which 29 (76.3%) were laboratory
      confirmed. There have been four outbreaks of measles, total of 12 people. The
      highest incidence was observed in patients 25-29 years old (0.28/100,000), then
      in 30-34 (0.26/100,000). 23 people were hospitalized (60.5%). No death from
      measles was reported. Vaccination status of children and youth aged 2 to 11 years
      ranged from 84.4% to 99.7% (primary vaccination in children born in 2010 - 2005)
      and from 53.7% to 60.3% (booster, in born 2004 - 2000). SUMMARY AND CONCLUSIONS:
      The epidemiological situation of measles in 2011, worsen in relation to the
      previous year. A persistent low number of suspected cases of measles indicates
      low sensitivity of the surveillance system.

PMID- 24040713
TI  - Mumps in Poland in 2011.
AB  - INTRODUCTION: In 2011, similarly to previous years a decline was observed in the
      number of recorded cases of mumps. This favourable epidemiological situation is a
      result of mumps vaccination program, which from 2003 became mandatory given as
      two dose schemes with MMR vaccine (mumps, measles, and rubella). AIM: The aim of
      this work was to assess mumps epidemiological situation in Poland in 2011, in
      comparison to previous years. MATERIAL AND METHODS: The assessment of mumps
      epidemiological situation in Poland in 2011 was conducted by using the results of
      analyzed data for infectious diseases published in a yearly bulletin "Infectious
      diseases and poisoning in Poland in 2011" and in yearly bulletin "Preventative
      immunisation in Poland in 2011" Czarkowski MP and in, Warsaw, NIZP- PZH and GIS.
      Also used "Case definitions for infectious disease developed for epidemiological
      surveillance in the years 2009-2011 " (Department of Epidemiology, NIZP-PZH), as
      well as Preventative vaccination program 2011. RESULTS: In 2011 there were 2585
      reported cases of mumps. Incidence of mumps was lower 6.7/100 in comparison with
      2010 (7.2/100), as well as almost twice lower than a median for the years 2005
      2009. The highest incidents rate of mumps 52.0/100,000 was recorded among
      children at the age 5-9 years of age. Incidence in women was lower (5.6) than in
      men (7.9). In 2011, 24 people were hospitalized due to mumps. CONCLUSION:
      Systematic implementation of vaccination program against mumps as according to
      Inoculation Calendar has resulted in a significant decline in the number of
      reported cases.

PMID- 24040714
TI  - Rubella in Poland in 2011.
AB  - INTRODUCTION: Since 2004 rubella is covered by the Program for the Elimination of
      Rubella of the World Health Organization (WHO). The aim of the Program is to
      interrupt transmission of rubella virus in the environment and prevention of
      congenital rubella cases in children. In Poland, the vaccination against rubella
      to 2003 were limited to women, which in turn resulted in an increase in the
      incidence of rubella among men, and hence a possibility of infection in
      susceptible pregnant women. PURPOSE OF THE STUDY: To assess the epidemiological
      situation of rubella in Poland in 2011, taking into account the vaccination
      coverage against rubella in the general population and in selected birth cohorts.
      MATERIAL AND METHODS: Evaluation of rubella epidemiological situation in Poland
      was based on data from the newsletters: "Infectious diseases and poisoning in
      Poland in 2011" and, "Vaccinations in Poland in 2011" (MP. Czarkowski, Warsaw
      2012, NIPH-NIH, GIS). Classification of rubella cases was based on the definition
      of infectious diseases prepared by ECDC. RESULTS: In 2011, there was a slight
      increase in the incidence of rubella, compared to 2010 (from 11.0/100,000 to
      11.1/100,000). Total of 4 290 cases were registered. The highest incidence,
      regardless of gender and the environment, has been among children 5 years old
      (94.1/100,000.) and 6-year-old (93.4/100,000). As in 2010, the incidence of
      rubella in girls and women was lower than the incidence in boys and men
      (9.6/100,000 versus 12.8/100,000.). In 2011 there were no recorded cases of
      congenital rubella. CONCLUSIONS: Still small proportion of reported rubella cases
      are laboratory confirmed. In 2011 it amounted to 0.2% of cases. This situation
      requires prompt improvement.

PMID- 24040715
TI  - Chickenpox in Poland in 2011.
AB  - INTRODUCTION: A number of chickenpox cases which occur in children indicate the
      rationality of the use of preventive vaccination. In Poland since 2002,
      chickenpox vaccination is recommended. AIM OF THE STUDY: The aim of this study
      was to assess the epidemiological situation of chickenpox in Poland in 2011 and
      to compare with the situation in the previous years. MATERIALS AND METHODS:
      Assessment of the epidemiological situation chickenpox in 2011 in Poland was
      based on analysis of the data published in the annual bulletins: "Infectious
      diseases and poisonings in Poland in 2011." and "Immunization Safety in Poland in
      2011 (Czarkowski MP. Et al., Warsaw, NIPH-NIH, GIS). In addition, on data from
      the "Immunization Program for 2011" (Annex to the Statement of the Chief Sanitary
      Inspector on Oct. 28, 2010). RESULTS: In 2011. 172 855 registered cases of
      chickenpox were registered in Poland n 2011. Incidence was 448.7/100. It was
      lower than in 2010. (480.4/100,000). Highest incidence was in Mazowieckie, the
      lowest in Podlaskie. Across the age groups the highest incidence (3708.7/100,000)
      was reported in age group 5-9. The incidence of chickenpox in men (472.3/100,000)
      was higher than in women (426.5/100,000). In inhabitants of rural areas it was
      higher (473.5) than among urban residents (432.7/100,000). Number of hospitalized
      cases was 1 016. Number of people vaccinated against chickenpox amounted to 38
      943 people. SUMMARY: In 2011 there was small decrease in the incidence of
      chickenpox. But the rising trend is continuing in Poland since 2004. It can be
      partly be explained by improved surveillance of the disease. Overall high
      incidence of chickenpox brings problem of widespread vaccination of children.

PMID- 24040716
TI  - Pertussis in Poland in 2011.
AB  - INTRODUCTION: Results of the nationwide Pertussis Epidemiology Study implemented
      by Department of Epidemiology NIPH-NIH in 2009-2011 showed a high proportion of
      cases of whooping cough in adults whose only symptom of Bordetella pertussis
      infection was long lasting cough. It should be noted that the infected adults
      pose a risk of transmission of infection to susceptible contacts such as infants.
      THE AIM OF THE STUDY: To assess the epidemiological situation of pertussis in
      Poland in 2011, including vaccine coverage of children. MATERIALS AND METHODS:
      Assessment of the epidemiology ofpertussis in Poland was based on analysis of
      individual reports of suspected cases of pertussis sent to the NIPH-NIH by the
      regional sanitary-epidemiological stations, data from the bulletin "Infectious
      diseases and poisonings in Poland in 2011" and bulletin "Immunizations in Poland
      in 2011 "(MP Czarkowski et al, Warsaw 2012, NIPH-NIH, GIS). RESULTS: In 2011,
      number of registered cases of whooping cough was 1 669. The incidence was 4.3 per
      100,000 children up to 15. It was higher than in the previous year (3.3/100,000)
      by 25.5%. The highest incidence occurred in children aged 3 years (20.8/100 000),
      and in people in the age group 10-14 years (20.3/100,000). Number of hospitalized
      persons was 648, (38.8%)of reported cases. In 2011, there were no deaths from
      whooping cough. SUMMARY AND CONCLUSIONS: Higher the incidence of pertussis
      observed in 2011, compared with the previous year, may indicate improved
      sensitivity of the surveillance system.

PMID- 24040717
TI  - Scarlet fever in Poland in 2011.
AB  - OBJECTIVE: Assessment of the epidemiological situation of scarlet fever in Poland
      in 2011 MATERIALS AND MATHODS: The evaluation was performed by analysing the data
      published in the bulletin, "Infectious diseases and poisonings in Poland in 2011"
      (Warsaw 2012, NIPH-NIH, CSI) and also in bulletins from previous years. RESULTS:
      Since 2004 in Poland has been observed epidemic increase in the number of scarlet
      fever cases. However, the growth rate is significantly slower and incidence is
      considerably lower than in previous epidemic periods. In 2011, in the country a
      total of 18 267 cases were registered and incidence was 47.4 per 100,000
      population (in provinces: from 23.4 in Lodzkie to 68.0 in Slaskie). The highest
      incidence was notified in 5-year-old and 6-year-old children (782.4), whereas the
      incidence of children and young people up to 15 years accounted for 96.9% of all
      cases. The incidence of men 53.7 by almost 30% was higher than the incidence of
      women (41.6). The incidence was higher in urban areas than in rural areas and was
      53.3 (in rural area 38.3). 1.1% of patients were hospitalized. No deaths were
      reported. SUMMARY: An impact on the epidemiological situation of scarlet fever in
      Poland in the last two decades have i.a. demographic changes--decline in the
      population of children, i.e. in group which is particularly vulnerable to
      infection. In order to raising the reliability of surveillance data, it is
      recommended a prominent heightening of the percentage of cases which clinical
      diagnosis would be confirmed by the result of bacteriological examination.

PMID- 24040718
TI  - Meningitis and encephalitis in Poland in 2011.
AB  - INTRODUCTION: About 2 000-3 000 cases of meningitis and/or encephalitis of viral
      or bacterial etiology are recorded every year in Poland. AIM OF THE STUDY: The
      aim of this study was to assess the epidemiology of meningitis and/or
      encephalitis in Poland in 2011 and compare it to the situation in previous years.
      MATERIALS AND METHODS: Assessment of the epidemiological situation of meningitis
      and/or encephalitis in Poland in 2011, was based on the results of analysis of
      epidemiological interviews sent to the NIZP-PZH by the Regional Sanitary
      Epidemiological Stations published in the annual bulletin "Infectious diseases
      and poisonings in Poland in 2011" and "Preventive immunizations in Poland in
      2011" (Czarkowski MP. et al., Warsaw, NIZP-PZH, GIS). RESULTS: In 2011 in Poland
      it was recorded 2 915 cases of meningitis and/or encephalitis. This included 1
      438 cases of viral etiology, 888 of bacterial etiology and 589 of other etiology
      specified or unspecified. Among the reported cases of bacterial meningitis and/or
      encephalitis dominant etiological factor was N. meningitidis (193), S. pneumoniae
      (192) and H. influenzae type B (11). Among the infections of viral etiology
      predominated was virus of tick-borne encephalitis (221). SUMMARY AND CONCLUSIONS:
      The epidemiological situation of inflammatory meningitis - meningitis and/or
      brain in Poland in 2011 compared to 2010 did not change significantly.

PMID- 24040719
TI  - Legionellosis in Poland in 2011.
AB  - OBJECTIVES: The main objective of this article is to assess the epidemiology of
      legionellosis in Poland in 2011, using national surveillance data. MATERIALS AND
      METHODS: We reviewed surveillance data published in the annual bulletin
      "Infectious diseases and poisonings in Poland" from 2005 to 2011, and
      legionellosis case reports from 2011 sent to the Department of Epidemiology NIPH
      NIH by Sanitary-Epidemiological Stations. RESULTS: In 2011, a total 18
      Legionnaires' disease (Legionnaires' pneumonia) cases was reported. Annual
      incidence rate (0.05 per 100,000 population) has dropped by more than 50%
      compared to previous year, but was similar to the median incidence reported in
      years 2005-2009. For several years, the legionellosis incidence varies for
      different regions, but generally is slightly higher in Mazowieckie province; the
      incidence among men (0.06 per 100,000) is slightly higher than the incidence
      among women (0.04). In 2011, only sporadic cases have been reported. All patients
      presented with pneumonia (no Pontiac fever cases) and were hospitalized. Four
      deaths related to the disease (in patients above 55 years of age) were reported.
      Source of infection was identified only in one hospital-acquired legionellosis.
      Furthermore, one case was associated with a treatment at a sanatorium; There were
      two imported cases associated with travel to Italy and France. CONCLUSIONS: We
      concluded, that national surveillance shall be shifted toward collecting more
      information about possible environmental sources of infection/exposures to
      Legionella.

PMID- 24040720
TI  - Shigellosis in Poland in 2011.
AB  - BACKGROUND: Shigellosis, also known as bacillary dysentery, is a contagious and
      infectious disease. In the European Union, on the basis of the Commission
      Decision of 2 April 2009 and the Commission Decision of 28 April 2008, a unified
      system for collecting epidemiological data on infectious diseases was introduced,
      including shigellosis. This makes it possible to compare data collected at
      different times and in different countries. AIM: The aim of the article is to
      evaluate the epidemiological situation of shigellosis in Poland in 2011.
      MATERIALS AND METHODS: An assessment of the epidemiological situation of
      shigellosis was based on the results from an analysis of the yearly annual
      bulletins: "Infectious diseases and poisonings in Poland in 2011", reports from
      bacteriological laboratories and reports from individual cases and
      epidemiological investigations of outbreaks linked to shigellosis, sent by
      Sanitary Epidemiological Stations to the Department of Epidemiology at NIZP-PZH.
      RESULTS: In Poland, 17 confirmed cases of shigellosis were registered in 2011.
      The incidence of 0.04 per 100,000 inhabitants was lower when compared to the
      previous year. The number of cases is lower by 48% when compared with the median
      of years 2005-2009--35 cases (incidence 0.09/100,000). Most of the cases were
      registered in the Silesian province--7 (incidence 0.15 /100,000). According to
      data from 16 laboratories of Sanitary Epidemiological Stations, Shigella was not
      detected among the subjects. All cases of shigellosis registered in 2011, were
      confirmed by a hospital laboratory at or a private laboratory. CONCLUSIONS: In
      Poland, we have observed a decline in the number of cases of shigellosis and the
      incidence remains at a relatively steady level and constitutes less than
      0.1/100,000 inhabitants. Compared to the rest of the countries belonging to the
      EU/EFTA, the current epidemiological situation of shigellosis in Poland is good.
      Poland is a country with the lowest incidence. In spite of this, the surveillance
      of shigellosis required more active epidemiological measures. Special attention
      should be paid to the bacteriological testing of people living in rural areas,
      children and young people.

PMID- 24040721
TI  - Yersiniosis in Poland in 2011.
AB  - AIM: The aim of this study is to assess the epidemiology of yersiniosis in Poland
      in 2011 compared to previous years. MATERIAL AND METHODS: We reviewed
      surveillance data published in the annual bulletin "Infectious diseases and
      poisonings in Poland" from 2006 to 2011 (MP Czarkowski et al., NIH and GIS) and
      individual yersiniosis case reports from 2011 sent by the Sanitary
      Epidemiological Stations. Additionally, we use data from the Department of
      Demographic Surveys in Central Statistical Office. RESULTS: In Poland in 2011 a
      total of 257 yersiniosis cases were reported including 238 cases of intestinal
      and 19 cases of extraintestinal yersiniosis; 74% of patients were hospitalized.
      The incidence rate was 0.67 per 100,000 inhabitants. No deaths related to the
      disease were reported. The most affected group in intestinal infections were
      children younger than 4 (63% of all cases); symptoms usually involved diarrhea
      (87%), fever (76%), abdominal pain (47%) and vomiting (31%). Extraintestinal form
      of infection was less common than in 2010 (27 cases) and usually involved
      symptoms from the osteoarticular system, noted in 79% of patients (15 cases).
      Similarly to previous year (2010) most cases of yersiniosis were reported from
      Mazowieckie province (91), and the least from the Podlaskie province (1).
      Serological types of Yersinia enterocolitica were identified in 102 cases
      (39.7%): serotype O8 (56.8%), O3 (41%) and O9 (> 2%). There was one household
      outbreak involving 4 people. CONCLUSIONS: Since 2006 in Poland in some areas of
      the country, occurrence of endemic infections caused by a type O8 is observed. A
      large percentage (60.3%) of unknown Yersinia serotypes is a consequence, that
      physicians do not always request serotyping. Additionally, the relatively low
      number of reported cases of extraintestinal yersiniosis in Poland may suggest
      underreporting, especially by rheumatological hospitals.

PMID- 24040722
TI  - Campylobacteriosis in Poland in 2011.
AB  - THE AIM OF THE STUDY: To assess the epidemiological situation of
      campylobacteriosis in Poland in 2011 as compared with the situation in 2010.
      MATERIALS AND METHODS: The assessment was based on the results of the analysis of
      data from the annual bulletin "Infectious diseases and poisonings in Poland",
      2010-2011 (MP Czarkowski et al., NIH and GIS), information from the forms of
      individual cases and epidemiological investigations forms on outbreaks of
      campylobacteriosis, which were sent by the Sanitary-Epidemiological Stations to
      the Department of Epidemiology and data from the Department of Demographic
      Studies of the Central Statistical Office. All cases were classified according to
      a surveillance case definition. RESULTS: In 2011, number of campylobacteriosis
      cases registered in Poland was 354, the incidence rate was 0.92/100,000. All
      cases were reported as confirmed. No deaths were recorded. More than 61% of
      reported cases came from two provinces--Slaskie 112 (31%) and Warminsko-mazurskie
      104 (29%). The highest incidence was observed in Warminsko-Mazurskie
      (7.16/100,000). Hospitalized were 57.5%. The lowest percentage of hospitalization
      (31.3%) was in Slaskie. In six provinces all reported cases were hospitalized.
      Campylobacter species was determinated in 282 patients (79.7%). It was found that
      270 cases were caused by C. jejuni and 12 by C. coli. The majority of cases (264,
      74.6%) occurred in the age group 0 - 4, Among the cases were 217 men and 127
      women. In 2011, one family outbreak was caused by Campylobacter. CONCLUSION: In
      Poland, campylobacteriosis is rarely diagnosed and recorded. Routine diagnosis of
      infection with Campylobacter is done in two provinces only.

PMID- 24040723
TI  - Foodborne botulism in Poland in 2111.
AB  - OBJECTIVES: The main objective of this article is to assess the epidemiology of
      foodborne botulism in Poland in 2011, using national surveillance data. MATERIALS
      AND METHODS: We reviewed surveillance data published in the annual bulletin
      "Infectious diseases and poisonings in Poland" from 2005 to 2011, and botulism
      case reports from 2011 sent to the Department of Epidemiology NIPH-NIH by
      Sanitary-Epidemiological Stations. RESULTS: In 2011, a total of 35 foodborne
      botulism cases (including 21 laboratory confirmed cases) was reported,
      corresponding to the one of the lowest annual incidence rate (0.09 per 100,000
      population) since the introduction of botulism as mandatory notifiable disease.
      The higher incidence rates compared to the previous year were in the Warminsko
      Mazurskie, Kujawsko-Pomorskie, Lubelskie, Podkarpackie, Mazowieckie and
      Dolnoslaskie. Incidence in rural areas (0.13 per 100,000 population) was higher
      than the incidence in urban areas (0.07). Men, had more than 3,5 times higher
      incidence than women; the highest incidence rate (0.23 per 100,000 population)
      was observed among men in the age group of 60 + years. Most cases were associated
      with consumption of commercially canned meat (including pork and other types of
      meat). Home canned foods containing meats or vegetables and meats were also a
      common vehicle. Almost all cases were hospitalized (33 cases). One death related
      to the disease was reported. CONCLUSIONS: In 2011, in Poland epidemiology of the
      foodborne botulism remains stable. From the point of view of national
      surveillance, it is necessary to increase the percentage of cases investigated
      with laboratory tests.

PMID- 24040724
TI  - Hepatitis A in Poland in 2011.
AB  - AIM: The aim of the article is evaluation of the epidemiological situation of
      hepatitis A in Poland in 2011. MATERIALS AND METHODS: Assessment of
      epidemiological situation of hepatitis A was based on results from analysis of
      the annual bulletins: "Infectious diseases and poisonings in Poland in 2011",
      "Vaccinations in Poland in 2011", reports from individual cases and
      epidemiological investigations of outbreaks linked to hepatitis A, sent by
      Epidemiological Departments in Sanitary Epidemiological Stations to the
      Department of Epidemiology at NIZP-PZH. RESULTS: In Poland, 65 cases of hepatitis
      A were registered in 2011. The incidence of 0.17/100,000 was lower them in the
      previous year. The incidence of hepatitis A ranged from 0.07/100,000 in
      Dolnoslaskie province to 0.52/100,000 in Slaskie province. The incidence of
      hepatitis A in men (0.19) was higher than in woman (0.15). Imported cases
      constituted 49.2% (32 cases) of the overall number of cases of hepatitis A. There
      were two outbreaks of hepatitis A involving 7 cases registered in 2011.
      CONCLUSIONS: In the year 2011, a decrease in the number of cases was noted in
      comparison with the median of years 2008 - 2010. Despite the fact that the
      current epidemiological situation of hepatitis A in Poland is good, the disease
      still requires monitoring and analysis within the framework of epidemiological
      surveillance system.

PMID- 24040725
TI  - Hepatitis B in Poland in 2011.
AB  - OBJECTIVES: Evaluation of the epidemiological situation of hepatitis B in Poland
      in 2011 in comparison with previous years. MATERIALS AND METHODS: Evaluation of
      occurrence of hepatitis B in Poland, registered in 2011, based on the results of
      the analysis of case-based data for acute hepatitis B sent to the NIPH-NIH by the
      State Sanitary Inspection and on aggregate data from annual bulletin "Infectious
      diseases and poisonings in Poland". RESULTS: A total of 1,583 hepatitis B cases,
      including 30 cases of co-infection with hepatitis C (HCV) was reported in 2011.
      Incidence was 4.11 per 100,000 population and was lower by 4% compared to the
      previous year. Acute cases constituted 6.6% of all hepatitis B cases, the
      incidence - 0.27 per 100,000 population. The highest incidence of acute hepatitis
      B recorded in Podlaskie (1.00 per 100,000 population) and that of chronic in
      Opolskie (10.83 per 100,000). Overall, hepatitis B occurred more often in males
      than females and those residing in urban areas. Chronic hepatitis B was most
      frequently detected (as in previous years) in people aged 15-19, most rarely in
      those aged 0-14 entirely covered by universal HBV vaccination of infants. The
      highest incidence of acute hepatitis B was observed among people aged 30-34 (0.64
      per 100,000) and among those aged 65-74 (0.58 per 100,000). Predominant route of
      infection hepatitis B in Poland were medical procedures (in 55% of all acute
      cases). Among young people (aged 25-34) have been observed increasing share of
      infections acquired through sexual contact or intravenous drug use (28% of acute
      cases), among elderly people nonmedical routes of infection constituted only 7%
      and mostly it was the contact with infected household member. In 2011, eight
      people died because of acute hepatitis B and 40 due to chronic hepatitis B.
      CONCLUSIONS: Observed steady downward trend in incidence of acute hepatitis B
      indicates persistent effectiveness of the universal HBV vaccination program. In
      view of growing share of acute cases acquired by sexual transmission or drug use
      it is reasonable to recommend vaccinations to unvaccinated at-risk people
      especially those exposed to HBV infection due to lifestyle.

PMID- 24040726
TI  - Hepatitis C in Poland in 2011.
AB  - BACKGROUND: Low percent of diagnosed HCV infections is an important public health
      problem in Poland. Registered trends of HCV incidence compared to prevalence data
      allow to interpret the diagnosis rate in different groups. AIM: To assess
      epidemiological situation of hepatitis C in Poland in 2011 in comparison to
      preceding years. METHODS: The descriptive analysis was based on data retrieved
      from routine mandatory surveillance system. Case classification according to 2005
      definition and 2009 definition was verified on a basis of individual case
      reports. RESULTS: In total there were 2151 hepatitis C cases meeting the 2005
      case definition registered in 2011 (incidence 5.58 per 100,000) and the
      increasing trend observed since 2009 was continued. With respect to the estimated
      number of prevalent cases the diagnosis rate was 78 per 10,000. This indicator
      was lower for the rural areas, for the age group 30-49 and varied significantly
      across regions. The increasing trend of mortality is also of note (2009--137
      deaths; 2010--167, preliminary data for 2011--191, mortality 0.5 per 100,000)
      CONCLUSIONS: The increasing hepatitis C incidence may be a result of
      intensification of testing activities. Low indicator of diagnosis rate and the
      increasing mortality call for improvement in access to diagnosis and treatment.

PMID- 24040727
TI  - Tetanus in Poland in 2011.
AB  - PURPOSE OF THE STUDY: Tetanus epidemiological assessment of the situation in
      Poland in 2011. MATERIALS AND METHODS: We used the data published in the annual
      bulletin "Infectious diseases and poisonings in Poland in 2011" and "Vaccinations
      in 2011" (NIPH-NIH-Department of Epidemiology, GIS - Department of Prevention and
      Control of Infectious Diseases in Humans - Warsaw 2012) and individual reports
      sent to the Department of Epidemiology NIPH-NIH RESULTS: In 2011 there were
      reported 14 cases of tetanus--(incidence 0.036/100 000) two less than in 2010.
      The patients were aged 50 years or more. Among them 4 persons were vaccinated. In
      remaining 10 cases there was a lack of data on vaccination. 5 patients died
      (35.7%). CONCLUSIONS: The incidence of tetanus in Poland occurs mostly in people
      aged above 50 years of age. Vaccination should be promoted among the elderly in
      the recommended intervals, every 10 years.

PMID- 24040728
TI  - Lyme disease in Poland in 2011.
AB  - INTRODUCTION: In Poland registration of all cases of Lyme disease is conducted by
      Epidemiological Unit of National Institute of Public Health - National Institute
      of Hygiene. Most cases of Lyme disease occur in the North- East region of Poland;
      however it is important to note that the disease is no longer solely a problem of
      this region of Poland. OBJECTIVES: The aim of this work is the assessment of the
      epidemiological situation of Lyme disease in Poland in 2011 as compared to the
      situation in the previous years. MATERIALS AND METHODS: Assessment of the
      epidemiological situation of Lyme disease in Poland was made on the basis of an
      analysis of individual notifications of suspected Lyme disease submitted to NIZP
      NIH by the Provincial Sanitary- Epidemiological stations; as well as data from
      "Infectious diseases and poisoning in Poland in 2011" bulletin, and "Preventative
      vaccination in Poland in 2011" bulletin (MP Czarkowski and Co, Warsaw 2012, NIZP-
      PZH, GIS). RESULTS: In 2011 there were 9 157 registered cases of Lyme disease and
      it is 2% higher than in the previous year. The overall incidence in the country
      amounted 23.8 per 100,000 population. The highest recorded in Podlaskie province
      75.5 per 100,000 population. 2091 people were hospitalized due to Lyme disease.
      SUMMARY AND CONCLUSIONS: In 2011 there was a tendency to slow down/inhibit the
      incidence of Lyme disease. The registered number of cases was comparable to the
      previous year. There is still fairly low percentage of confirmed cases by
      performing diagnostic test Western blot method.

PMID- 24040729
TI  - Trichinellosis in Poland in 2011.
AB  - PURPOSE OF THE STUDY: The purpose of the study was assessment of the
      epidemiological situation of trichinellosis in Poland in 2011. MATERIALS AND
      METHODS: The evaluation was carried out on the basis of the analysis of data from
      the bulletin "Infectious diseases and poisonings in Poland. 2010". information
      from the questionnaires of individual cases and epidemiological investigations of
      the outbreaks of trichinellosis sent by the Sanitary-Epidemiological Stations and
      on data from Demographic Research Department of the Central Statistical Office.
      Cases were classified according to the current case definition. RESULTS: In 2011.
      Poland recorded 23 cases of trichinellosis cases. The incidence was 0.06/100,000.
      There were reported 10 confirmed cases and 13 probable. There were no deaths from
      trichinellosis, but over 91% of infected persons were hospitalized. In 2011 three
      outbreaks of trichinellosis were recorded. One of them occurred in Dolnoslaskie
      district, where cases of the infection are recorded sporadically. The
      epidemiological investigations established that the cause of the outbreak was
      consumption of wild boar meat products, mainly raw sausage. Trichinella
      containing meat products are prepared primarily for personal use. but are also
      distributed among family and friends. CONCLUSION: The annually repeating
      outbreaks of trichinellosis mainly among family members indicates insufficient
      awareness of the risk of parasitic diseases caused by consumption of products
      containing raw or half raw meat of animals. Of the particular importance is to
      inform those who will give the carcases of animals to test about the limitations
      of the test method used.

PMID- 24040730
TI  - Invasive tapeworm infections in Poland in 2011.
AB  - The aim of this work was to assess the epidemiological situation of
      echinococcosis and cysticercosis in 2011 as compared to previous years. MATERIALS
      AND METHODS: Assessment of the epidemiological situation was carried out on the
      basis of individual data submitted to NIZP-NIH by the District Sanitary-
      Epidemiological Stations as well as from data gathered from annual bulletins
      "Infectious diseases and poisoning in Poland". RESULTS: In 2011 there were in
      total 19 registered cases of echinococcosis; unspecified, E. granulosus, and E.
      multilocularis. Incidence was 0.049/100,000. The highest incidence was recorded
      in Podlaskie district (0.333/100,000). The reported cases occurred in adults
      between the age of 34 and 74 (average 56.4; median 58), more often in women
      (incidence 0.055) than in men (incidence 0.043). Incidence of echinococcosis was
      higher in the country (0.079) than in the city (0.030). The percentage of
      reported cases in which the species of a tapeworm was identified was 63%, and
      within that 42% were infections with E. granulosus, and 21% with E.
      multilocularis. In 2011 there were two registered cases of cysticercosis and the
      incidence was 0.005 per 100,000 population. CONCLUSION: It seems necessary to
      consider the introduction of obligatory differentiation tests for E. granulosus
      and E. multilocularis infections. It is also important to introduce a definition
      of cysticercosis for the purpose of epidemiological surveillance. It is
      recommended to intensify health promotion, including education targeted at
      reducing the risk of contracting invasive tapeworm infections.

PMID- 24040731
TI  - HIV and AIDS in Poland in 2011.
AB  - INTRODUCTION: From 1985 until the end of 2012 16,314 cases of HIV infection,
      2,848 AIDS cases and 1,185 deaths of AIDS patients were registered in Poland.
      OBJECTIVE: To analyze the epidemiological situation of newly diagnosed HIV
      infections and AIDS cases in Poland in 2011. MATERIALS AND METHODS: Descriptive
      analysis of newly detected HIV cases and incident AIDS cases was performed based
      on routine notifications by clinicians and laboratories. Data on the number of
      HIV tests from annual survey among laboratories were also used. RESULTS: In 2011
      there were 1,105 HIV cases diagnosed in Poland (detection rate 2.87 per 100,000
      population), including 23 among non-Polish citizens. The total number of AIDS
      cases was 175 (incidence 0.45 per 100,000) and 65 AIDS patients died. Compared to
      2010, there was an increase in infections diagnosed among men who have sex with
      men (MSM) (from 51.9% to 67.1% of cases with known transmission mode). HIV
      infection is mainly detected among people aged 20 to 39 years (69.9%) and among
      males (82.2%). The percentage of late presenters (defined by the time between HIV
      and AIDS diagnoses of less than 3 months) remained at the same level as in 2010
      (9.2% of newly diagnosed HIV infections). CONCLUSIONS: Assessment of
      epidemiological situation is limited by the missing data on the probable
      transmission route in a large percentage of reports of newly diagnosed HIV cases.
      The significant increase of HIV infections among MSM call for strengthened
      prevention measures in this group.

PMID- 24040732
TI  - Malaria in Poland in 2011.
AB  - THE AIM OF THE STUDY: To assess the epidemiological situation of malaria in
      Poland in 2011 as compared with previous years. MATERIALS AND METHODS: evaluation
      of incidence of malaria registered in Poland in 2011, based on the results of the
      analysis of individual reports sent to the NIPH-NIH by the Sanitary
      Epidemiological Stations and on aggregate data published in the annual bulletin
      "Infectious diseases and poisonings in Poland." Case classification in the
      epidemiological surveillance based on case definition for malaria approved by EC
      in the EU countries in 2008. Only symptomatic laboratory-confirmed cases were
      recorded. RESULTS: In 2011 14 cases of malaria were registered in Poland. All
      were imported from malaria-endemic countries: 64% of the cases were brought from
      Africa, and 21% from Asia. In comparison with the previous year number of
      reported cases was smaller by 21 cases. No deaths were reported. In one person
      who did not leave Poland in the last year there was probably a recurrence of
      malaria, though Plasmodium species has not been established. Among the cases with
      species-specific diagnosis 7 (63%) were caused by P. falciparum, 2 (18%) by P.
      vivax and P. malariae in one. Also in one case the mixed invasion was found. In
      50% of cases the infection occurred during work-related trips, 43% in tourist
      trips and in one case, the student fell ill, who was in Cameroon a year earlier.
      Chemoprophylaxis was applied to five people but only in one person appropriately.
      In 2011, in connection with an outbreak of malaria in Greece, restrictions on
      blood donation for returnees from certain regions of Greece were implemented.
      CONCLUSIONS: Despite marked fluctuations in the total annual number of reported
      cases, incidence in Poland remains low. The main problem for the Polish imported
      malaria remains seriousness of illness in many patients, most often as a result
      of delayed diagnosis.

PMID- 24040733
TI  - Tuberculosis in Poland in 2011.
AB  - AIM OF THE STUDY: To evaluate the main features of TB epidemiology in 2011 in
      Poland and to compare with the corresponding EU data. METHODS: Analysis of case-
      based clinical and demographic data on TB patients from Central TB Register, of
      data submitted by laboratories on anti-TB drug susceptibility testing results in
      cases notified in 2011, data from National Institute of Public Health- National
      Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, from
      Central Statistical Office on deaths from tuberculosis based on death
      certificates, data from ECDC report "Tuberculosis surveillance in Europe 2011".
      RESULTS: 8478 TB cases were reported in Poland in 2011. The incidence rate was
      22.2 cases per 100,000, with large variability between voivodeships from 12.8 to
      37.0. The mean annual decrease of TB incidence in 2007 - 2011 was 0.4%. 7515
      cases had no history of previous treatment i.e. 19.7 per 100,000. The number of
      all notified pulmonary tuberculosis cases was 7879 i.e. 20.6 per 100,000. The
      proportion of extrapulmonary tuberculosis was 7.1% (599 cases). TB was diagnosed
      in 111 children (1.3% of all cases, incidence 1.9). The incidence of tuberculosis
      increased with age to 41.9 among patients 65 years old and older. The mean age of
      TB patients was 53.3 years. The incidence among men i.e. 31.0 was more than two
      times higher than among women i.e. 14.0. The incidence in rural population was
      slightly lower than in urban, respectively 21.9 and 22.4. Bacteriologically
      confirmed cases (5327) constituted 67.6% of all pulmonary TB cases. The number of
      smear positive pulmonary TB cases was 2916 (37.0% of all pulmonary cases). There
      were 38 foreigners registered among all cases of tuberculosis in Poland and 204
      cases registered among prisoners. There were 41 patients with MDR-TB (0.8% of
      4993 cases with DST results). TB was initial AIDS indicative disease in 26 cases.
      There were 575 deaths due to tuberculosis in 2010 (1.5 TB deaths per 100,000).
      Mortality among males--2.5--was four times higher than among females--0.6.
      CONCLUSIONS: In Poland the incidence of tuberculosis is higher than the average
      in EU countries. In 2011 the highest incidence occurred in older age groups and
      was higher in men. Positive characteristic also when compared with the situation
      in many EU countries is the low incidence of tuberculosis in children and the low
      percentage of patients with drug-resistant tuberculosis.

PMID- 24040734
TI  - Sexually transmitted diseases in Poland in 2011.
AB  - THE AIM OF THE STUDY: Was to assess epidemiological situation of sexually
      transmitted diseases in Poland in 2011. MATERIALS AND METHODS: Analysis of the
      data on prevalence of syphilis, gonorrhoea, non-gonococcal urethritis, genital
      herpes and genital warts was gathered from yearly reports MZ-14 from several
      didtricts. RESULTS: In 2011 there were 841 reported cases of all types of
      syphilis, which was higher by 24 than in 2010. Within the reported cases, 554
      cases were of early syphilis, 274 cases of late syphilis, and 11 cases of
      congenital syphilis. Syphilis during pregnancy and childbirth was reported in 13
      women. The highest incidence of syphilis in 2011, similarly to previous years was
      in Mazowieckie district (4.7/100,000) and the lowest in Swietokrzyskie district
      (0.2/100,000), the average in a whole country accounted to 2.2/100,000. In 2011
      there were 351 cases of gonorrhoea reported, which was higher by 77 cases than
      reported in the previous year. The highest incidence was reported in Mazowieckie
      voivodeship. Non-gonococcal urethritis -NGU was identified in 484 persons; this
      was less by 294 cases than reported in the previous year. The highest incidence
      rate was reported in Dolnoslaskie voivodeship 9.6/100,000. There were 428 cases
      of genital warts reported which was less by 174 cases than reported in 2010. The
      highest incidence rate was reported in Mazowieckie voivodeship, Warminsko-
      Mazurskie voivodeship and Kujawsko-Pomorskie voivodeship. As in previous years
      the most unfavourable epidemiological situation in terms of all registered
      sexually transmitted diseases was in Mazowieckie voivodeship. CONCLUSION: In 2011
      among sexually transmitted diseases NGU and genital warts were reported in lower
      numbers then in previous year. In the same time numbers of reported cases of
      gonorrhoea and syphilis increased. There is a continued decrease in the number of
      serological tests done for syphilis. Epidemiological indicators of treatment for
      gonorrhoea and syphilis are very low for number of years. The epidemiological
      data is probably incomplete due to the low sensitivity of reporting.

PMID- 24040735
TI  - Therapeutic recommendations for 2013: antiviral treatment for chronic hepatitis
      B.

PMID- 24040736
TI  - [Health situation of the Polish population and its determinants].

PMID- 24040737
TI  - [The health situation of the Polish population and its determinants. Author's
      rely].

PMID- 24040738
TI  - The ACPE supervisory education process: an historical perspective.
AB  - As the number of Clinical Pastoral Education students increases, supervisors in
      the Association for Clinical Pastoral Education (ACPE) are in short supply due to
      retirements. We explore factors associated with this supply problem, reporting
      here four results from our survey of active and retired supervisors. We identify
      the ages of the current supervisory pool, the ages at which supervisors were
      certified and the length of time spent in the supervisory education program
      across the decades. The survey results also identify what supervisors perceive as
      the most helpful components of their supervisory education. These four results
      identify trends across the decades that may be associated with the present and
      future shortages of supervisors.

PMID- 24040739
TI  - Ethics in pastoral care and counseling: a contemporary review of updated
      standards in the field.
AB  - This article reviews ethical responsibilities that must be considered when
      engaging in pastoral care, counseling, and psychotherapy. It discusses important
      contemporary issues counselors will want to contemplate in pursuing a high
      quality of care in their counseling practices. Examples and case studies are
      provided. Readers will be able to: Understand the function of ethical standards
      in the practice of counseling Be able to differentiate between pastoral care,
      pastoral counseling, and pastoral psychotherapy and their ethical implications
      Understand the importance of identifying one's limitations in counseling
      situations and how to proceed under such circumstances. Understand the need for
      pastoral counselors to attain the necessary credentials for practice in the area
      of counseling they intend to undertake. Become aware of the legal requirements
      when engaged in a counseling relationship.

PMID- 24040740
TI  - Religious counseling in the penal context: strategies of trust and establishment
      of trusting relationships in a context of distrust.
AB  - The paper describes how distrust shapes the network of relationships between the
      different agents in the penal context, among inmates, between inmates and their
      family, between inmates and staff, between counselors and staff, and between
      inmates and counselors, and discusses how counseling strategies need to be
      adjusted to counter the effects of the institutional and biographical context of
      distrust. The paper is based on many years of participation and observation in
      the context of Hong Kong.

PMID- 24040741
TI  - I stay and I follow: clerical reflections on pastoral care for victims of sexual
      abuse.
AB  - In this focus group study with clerics from the Church of Sweden, the Catholic
      Church, and the Free Church Movement, experiences of pastoral care for victims of
      sexual abuse were explored. The material was analyzed using thematic analysis.
      The participants expressed a wish to offer the best care possible. However,
      insecurity, a perceived lack of psychological competences, and restrictions
      imposed by the vow of silence provoked self-protective strategies that may affect
      both clerics and confidants.

PMID- 24040742
TI  - Discerning lived spirituality: the reception of otherness.
AB  - A previous article focused on an analysis of prominent conceptualizations of
      spirituality in health care. The encompassing character of those approaches was
      viewed as problematic because too little attention is paid to the distinctiveness
      and particularities of spiritual experience. This article argues that the
      criteria gleaned from the prior analysis provide an impetus for a constructive
      discernment proposal of lived spirituality. The experience of otherness is
      provides a central clue to an understanding of spirituality particularly by two
      key terms, receptivity and transformation, as central characterizations of lived
      spirituality. These terms are investigated as they embrace operational potential
      for chaplaincy care. The article concludes with a reflection on chaplaincy care
      as it relates to spiritual practice.

PMID- 24040743
TI  - Infant baptism: an evangelical chaplain's enlightenment.

PMID- 24040744
TI  - CO2 adhesion on hydrated mineral surfaces.
AB  - Hydrated mineral surfaces in the environment are generally hydrophilic but in
      certain cases can strongly adhere CO2, which is largely nonpolar. This adhesion
      can significantly alter the wettability characteristics of the mineral surface
      and consequently influence capillary/residual trapping and other multiphase flow
      processes in porous media. Here, the conditions influencing adhesion between CO2
      and homogeneous mineral surfaces were studied using static pendant contact angle
      measurements and captive advancing/receding tests. The prevalence of adhesion was
      sensitive to both surface roughness and aqueous chemistry. Adhesion was most
      widely observed on phlogopite mica, silica, and calcite surfaces with roughness
      on the order of ~10 nm. The incidence of adhesion increased with ionic strength
      and CO2 partial pressure. Adhesion was very rarely observed on surfaces
      equilibrated with brines containing strong acid or base. In advancing/receding
      contact angle measurements, adhesion could increase the contact angle by a factor
      of 3. These results support an emerging understanding of adhesion of, nonpolar
      nonaqueous phase fluids on mineral surfaces influenced by the properties of the
      electrical double layer in the aqueous phase film and surface functional groups
      between the mineral and CO2.

PMID- 24040745
TI  - Reactivity and dynamics of H2S, NO, and O2 interacting with hemoglobins from
      Lucina pectinata.
AB  - Hemoglobin HbI from the clam Lucina pectinata is involved in H2S transport,
      whereas homologous heme protein HbII/III is involved in O2 metabolism. Despite
      similar tertiary structures, HbI and HbII/III exhibit very different reactivity
      toward heme ligands H2S, O2, and NO. To investigate this reactivity at the heme
      level, we measured the dynamics of ligand interaction by time-resolved absorption
      spectroscopy in the picosecond to nanosecond time range. We demonstrated that H2S
      can be photodissociated from both ferric and ferrous HbI. H2S geminately rebinds
      to ferric and ferrous out-of-plane iron with time constants (taugem) of 12 and
      165 ps, respectively, with very different proportions of photodissociated H2S
      exiting the protein (24% in ferric and 80% in ferrous HbI). The Gln(E7)His
      mutation considerably changes H2S dynamics in ferric HbI, indicating the role of
      Gln(E7) in controling H2S reactivity. In ferric HbI, the rate of diffusion of H2S
      from the solvent into the heme pocket (kentry) is 0.30 MUM(-1) s(-1). For the
      HbII/III-O2 complex, we observed mainly a six-coordinate vibrationally excited
      heme-O2 complex with O2 still bound to the iron. This explains the low yield of
      O2 photodissociation and low koff from HbII/III, compared with those of HbI and
      Mb. Both isoforms behave very differently with regard to NO and O2 dynamics.
      Whereas the amplitude of geminate rebinding of O2 to HbI (38.5%) is similar to
      that of myoglobin (34.5%) in spite of different distal heme sites, it appears to
      be much larger for HbII/III (77%). The distal Tyr(B10) side chain present in
      HbII/III increases the energy barrier for ligand escape and participates in the
      stabilization of bound O2 and NO. 

PMID- 24040747
TI  - Unequivocal determination of site-specific protein disulfide bond reduction
      potentials by top-down FTICR MS: characterization of the N- and C-terminal redox
      active sites in human thioredoxin 1.
AB  - We report the reliable determination of equilibrium protein disulfide bond
      reduction potentials (E degrees ') by isotope-coded cysteine alkylation coupled
      with top-down Fourier transform ion cyclotron resonance mass spectrometry (FTICR
      MS). This technique enables multiple redox-active sites to be characterized
      simultaneously and unambiguously without the need for proteolysis or site
      directed mutagenesis. Our model system was E. coli thioredoxin, and we determined
      E degrees ' for its CGPC active-site disulfide as -280 mV in accord with
      literature values. E degrees ' for the homologous disulfide in human thioredoxin
      1 (Trx1) was determined as -281 mV, a value considerably more negative than the
      previously reported -230 mV. We also observed S-glutathionylation of Trx1 and
      localized that redox modification to Cys72; E degrees ' for the intermolecular
      disulfide was determined as -186 mV. Intriguingly, that value corresponds to the
      intracellular glutathione/glutathione disulfide (GSH/GSSG) potential at the redox
      boundary between cellular differentiation and apoptosis. 

PMID- 24040748
TI  - Transferrin-conjugated pluronic niosomes as a new drug delivery system for
      anticancer therapy.
AB  - An efficient tumor-targeted niosomal delivery system for the vehiculation of
      doxorubicin hydrochloride as an anticancer agent was designed. Niosomes were
      prepared from a mixture of an opportunely modified Pluronic L64 surfactant and
      cholesterol as a membrane additive and characterized in terms of size and related
      distribution function and drug entrapment efficiency. After the preparation,
      transferrin was conjugated to niosomes to produce transferrin (Tf) niosomes, and
      the cytotoxicity of the final formulation was studied. The specific uptake of Tf
      niosomes into cells was evaluated via incubation of MCF-7 and MDA-MB-231 cells
      with fluorescently rhodamine-loaded Tf niosomes for various times and
      concentration intervals and further investigated by fluorescence microscopy.
      Results showed that doxorubicin can be easily encapsulated into niosomes, which
      are regular and spherical in shape. Moreover, transferrin conjugate niosomes
      demonstrated far greater extents of cellular uptake by MCF-7 and MDA-MB-231
      cells, suggesting that they were mainly taken up by transferrin receptor-mediated
      endocytosis. Doxorubicin-loaded niosome anticancer activity was also achieved
      against MCF-7 and MDA-MB-231 tumor cell lines, and a significant reduction in
      viability in a dose- and time-related manner was observed. Finally, our
      formulation could be potentially useful as a target doxorubicin delivery system
      in anticancer therapy. 

PMID- 24040750
TI  - EBM and gut feelings.

PMID- 24040746
TI  - Cigarette smoke induces systemic defects in cystic fibrosis transmembrane
      conductance regulator function.
AB  - RATIONALE: Several extrapulmonary disorders have been linked to cigarette
      smoking. Smoking is reported to cause cystic fibrosis transmembrane conductance
      regulator (CFTR) dysfunction in the airway, and is also associated with
      pancreatitis, male infertility, and cachexia, features characteristic of cystic
      fibrosis and suggestive of an etiological role for CFTR. OBJECTIVES: To study the
      effect of cigarette smoke on extrapulmonary CFTR function. METHODS: Demographics,
      spirometry, exercise tolerance, symptom questionnaires, CFTR genetics, and sweat
      chloride analysis were obtained in smokers with and without chronic obstructive
      pulmonary disease (COPD). CFTR activity was measured by nasal potential
      difference in mice and by Ussing chamber electrophysiology in vitro. Serum
      acrolein levels were estimated with mass spectroscopy. MEASUREMENTS AND MAIN
      RESULTS: Healthy smokers (29.45 +/- 13.90 mEq), smokers with COPD (31.89 +/- 13.9
      mEq), and former smokers with COPD (25.07 +/- 10.92 mEq) had elevated sweat
      chloride levels compared with normal control subjects (14.5 +/- 7.77 mEq),
      indicating reduced CFTR activity in a nonrespiratory organ. Intestinal current
      measurements also demonstrated a 65% decrease in CFTR function in smokers
      compared with never smokers. CFTR activity was decreased by 68% in normal human
      bronchial epithelial cells exposed to plasma from smokers, suggesting that one or
      more circulating agents could confer CFTR dysfunction. Cigarette smoke-exposed
      mice had decreased CFTR activity in intestinal epithelium (84.3 and 45%, after 5
      and 17 wk, respectively). Acrolein, a component of cigarette smoke, was higher in
      smokers, blocked CFTR by inhibiting channel gating, and was attenuated by
      antioxidant N-acetylcysteine, a known scavenger of acrolein. CONCLUSIONS: Smoking
      causes systemic CFTR dysfunction. Acrolein present in cigarette smoke mediates
      CFTR defects in extrapulmonary tissues in smokers.

PMID- 24040749
TI  - Design and evaluation of a unique RT-qPCR assay for diagnostic quality control
      assessment that is applicable to pathogen detection in three species of salmonid
      fish.
AB  - BACKGROUND: The detection of pathogens at early stages of infection is a key
      point for disease control in aquaculture. Therefore, accurate diagnostic
      procedures are a must. Real-time PCR has been a mainstay in diagnostics over the
      years due to its speed, specificity, sensitivity, reproducibility and throughput;
      as such, real-time PCR is a target for improvement. Nevertheless, to validate a
      novel diagnostic tool, correct setup of the assay, including proper endogenous
      controls to evaluate the quantity and quality of the samples and to detect
      possible sample degradation, is compulsory. This work aims to design a unique RT
      qPCR assay for pathogen detection in the three salmonid species reared in Chile.
      The assay uses elongation factor 1 alpha as the single endogenous control, thus
      avoiding the need for multiple endogenous controls, as well as multiple
      validations and non-comparable quality control parameters. RESULTS: The in vivo
      and in vitro analyses of samples from Salmo salar, Oncorhynchus mykiss and
      Oncorhynchus kisutch showed that when primers were accurately selected to target
      conserved regions of the elongation factor 1 alpha (ELF1alpha) gene, a single
      novel RT-qPCR assay yielding similar and reproducible Ct values between the three
      species could be designed. The opposite occurred when an assay originally
      designed for Salmo salar was tested in samples from the two species of the genus
      Oncorhynchus. CONCLUSIONS: Here, we report the design and evaluation of an
      accurate trans-species RT-qPCR assay that uses the elongation factor 1 alpha
      (ELF1alpha) gene as an endogenous control and is applicable for diagnostic
      purposes in samples obtained from the three salmonid species reared in Chile.

PMID- 24040751
TI  - Functional plasticity of Th17 cells: implications in gastrointestinal tract
      function.
AB  - The gastrointestinal tract is an active player of the human immune system,
      participating in the innate and adaptive immune responses, keeping the
      homeostasis of the human being in a healthy status. However, most intestinal
      conditions are associated with an altered immune response, which implies the
      activation of CD4(+) T helper (Th) cells. Based on their cytokine secretion,
      transcription factor expression and immunological functions, the differentiated
      Th cells were initially subdivided into different lineages: Th1 (that express the
      transcription factor T-box (T-bet), secrete interferon (IFN)-gamma and protect
      the host against intracellular infections) and Th2 (that express GATA binding
      protein 3 (GATA-3), secrete interleukin (IL)-4, IL-5 and IL-13, and mediate host
      defense against helminths). Later, a new subset was identified, the Th17, which
      selectively produces IL-17A and is crucial for host defense against extracellular
      pathogens. More recently, a functional plasticity between the Th1 and Th17
      lineages has been described, a process sometimes controversial that seems to play
      a key role in different inflammatory conditions, including those affecting the
      gastrointestinal system. This review will summarize the current knowledge
      regarding the regulation and functional role of Th17 cells in the gut, focusing
      on these newly identified features of this T cell subset, including plasticity,
      their relationship with regulatory T cells and their heterogeneity in the
      inflammatory microenvironment. A better understanding of these issues is critical
      to elucidate the role of Th17 cells in intestine immunity, and so for the design
      of novel therapeutic approaches for intestinal diseases specifically targeting
      Th17 cells. 

PMID- 24040754
TI  - Semiconductive and magnetic one-dimensional coordination polymers of Cu(II) with
      modified nucleobases.
AB  - Four new copper(II) coordination complexes, obtained by reaction of CuX2 (X =
      acetate or chloride) with thymine-1-acetic acid and uracil-1-propionic acid as
      ligands, of formulas [Cu(TAcO)2(H2O)4].4H2O (1), [Cu(TAcO)2(H2O)2]n (2),
      [Cu3(TAcO)4(H2O)2(OH)2]n.4H2O (3), and [Cu3(UPrO)2Cl2(OH)2(H2O)2]n (4) (TAcOH =
      thymine-1-acetic acid, UPrOH = uracil-1-propionic acid) are described. While 1 is
      a discrete complex, 2-4 are one-dimensional coordination polymers. Complexes 2-4
      present dc conductivity values between 10(-6) and 10(-9) S/cm(-1). The magnetic
      behavior of complex 2 is typical for almost isolated Cu(II) metal centers.
      Moderate-weak antiferromagnetic interactions have been found in complex 3,
      whereas a combination of strong and weak antiferromagnetic interactions have been
      found in complex 4. Quantum computational calculations have been done to estimate
      the individual "J" magnetic coupling constant for each superexchange pathway in
      complexes 3 and 4. Compounds 2-4 are the first known examples of semiconductor
      and magnetic coordination polymers containing nucleobases. 

PMID- 24040752
TI  - The syllabic bridge: the first step in learning spelling-to-sound
      correspondences*.
AB  - It is widely agreed that learning to read starts with the establishment of letter
      to-phoneme correspondences. However, it is also widely agreed that prereaders do
      not have access to phoneme units. Here we show that the building of associations
      between letters and syllables, which we call the 'syllabic bridge', might be a
      faster and more direct way of learning spelling-to-sound correspondences in
      French. After a few minutes of exposure, prereaders are able to learn the
      statistical properties of letter co-occurrences. Statistical learning is boosted
      by explicit instructions about the associations between letter clusters and
      syllables. Building the syllabic bridge from available phonological syllables and
      frequent letter clusters may therefore be the first step in learning to read.

PMID- 24040753
TI  - Monolayer graphene/germanium Schottky junction as high-performance self-driven
      infrared light photodetector.
AB  - We report on the simple fabrication of monolayer graphene (MLG)/germanium (Ge)
      heterojunction for infrared (IR) light sensing. It is found that the as
      fabricated Schottky junction detector exhibits obvious photovoltaic
      characteristics, and is sensitive to IR light with high Ilight/Idark ratio of 2 *
      10(4) at zero bias voltage. The responsivity and detectivity are as high as 51.8
      mA W(-1) and 1.38 * 10(10) cm Hz(1/2) W(-1), respectively. Further photoresponse
      study reveals that the photovoltaic IR detector displays excellent spectral
      selectivity with peak sensitivity at 1400 nm, and a fast light response speed of
      microsecond rise/fall time with good reproducibility and long-term stability. The
      generality of the above results suggests that the present MLG/Ge IR photodetector
      would have great potential for future optoelectronic device applications. 

PMID- 24040755
TI  - A kinematic analysis of directional effects on mouse control.
AB  - The directional effects associated with cursor movement controlled by a computer
      mouse have long been studied to improve mouse performance during precise tasks.
      However, those studies have rarely considered the kinematic variables associated
      with directional effects and have only analysed the projection of trajectories
      along the main axes of movement, eventually reducing the original dimensions of
      the data. In addition, as the angle of approach has a limited number of levels,
      it has been difficult to observe singular behaviour in the horizontal directions.
      In this study, we investigated the directional effects on kinematic variables
      when using a mouse to select circular targets. In this experiment, the measured
      trajectory of 16 different angles of approach was measured after separating the x
      and y components. The results revealed interesting biomechanical and cognitive
      features of mouse control and led to the suggestion of two improvements to be
      made upon the typical mouse design. 

PMID- 24040756
TI  - Quinoline-based fluorescent probe for ratiometric detection of lysosomal pH.
AB  - A new pH-responsive fluorescent probe has been reported based on protonation
      activable resonance charge transfer. In aqueous solution, probe PQ-Lyso exhibits
      ratiometric detection of pH changes with a large hypsochromic shift of 76 nm and
      remarkable changes in the fluorescence intensity ratio (R = F(494 nm)/F(570 nm),
      R/R(0) = 105). Furthermore, PQ-Lyso, which is localized to lysosomes in living
      cells, can calibrate lysosomal pH using fluorescence ratiometry.

PMID- 24040757
TI  - Mechanism of the quenching of the tris(bipyridine)ruthenium(II) emission by
      persulfate: implications for photoinduced oxidation reactions.
AB  - A revised mechanism for the oxidation of the excited state of Ru(bpy)3(2+) with
      the persulfate anion is described in this work. The formation of the precursor
      complex in the electron transfer reaction involves ion pairing between the metal
      complex in ground and excited states and S2O8(2-). The equilibrium constant for
      the ion-pair formation (K(IP) = 2.7 M(-1)) was determined from electrochemical
      measurements and analysis of thermal reaction between Ru(bpy)3(2+) and
      persulfate. It was found to be consistent with the calculated value estimated
      from the Debye-Huckel model. The analysis of rate constants for reactions between
      persulfate and various metal complexes indicates that thermal and photochemical
      reactions most likely proceed through a common pathway. Extremely high
      reorganization energy (ca. 3.54 eV) for the electron transfer obtained from
      fitting experimental data with the Marcus equation is indicative of significant
      nuclear reorganization during the electron transfer step. In view of these
      results the electron transfer can be described as dissociative probably involving
      substantial elongation or complete scission of the O-O bond. The proposed model
      accurately describes experimental results for the quenching of *Ru(bpy)3(2+) over
      a wide range of persulfate concentrations and resolves some discrepancies between
      the values of K(IP) and k(et) previously reported. The implications of various
      factors such as the ionic strength and dielectric constant of the medium are
      discussed in relation to measurements of the quantum yields in photodriven
      oxidation reactions employing the Ru(bpy)3(2+)/persulfate couple.

PMID- 24040758
TI  - Mechanized and natural soil-to-air transfer of trifluralin and prometryn from a
      cotton field in Las Cruces, New Mexico.
AB  - Two pre-emergence herbicides (trifluralin and prometryn) were applied on a cotton
      field in Las Cruces, New Mexico, and their atmospheric particle and gas-phase
      concentrations were measured during mechanized soil preparation and natural wind
      erosion sampling events before and after herbicide application. Air sampling was
      conducted using samplers mounted at various heights from the ground and at
      various locations on the field. During mechanized soil management with a disk
      harrow, sampling occurred at two distances from the tractor ("near-source", 4 m
      downwind and "far-source", 20-100 m from the disking tractor). Natural background
      (no disking) sampling events occurred during daytime and at night. Both
      herbicides were quantifiable for all postapplication sampling events, including
      background sampling that occurred 8, 38, and 40 days after herbicide application.
      Average concentrations in both the gas and particle phases ranged from about 10
      to 350 ng/m(3). Averaging by event type, mean total prometryn concentrations were
      2 (night background) to 8 (near-source) times higher than the corresponding
      trifluralin concentrations. Prometryn/trifluralin ratios were higher in airborne
      samples than in soil, indicative of trifluralin losses during daytime sampling,
      possibly via atmospheric reactions. Prometryn particle phase mass fractions were
      generally higher than those for trifluralin for all sampling events, consistent
      with Kair/soil-oc partition coefficients, and particle-phase mass fractions were
      higher for near-source disking and daytime background sampling compared to far
      source and nighttime. Daytime natural background prometryn concentrations could
      be as high as those measured during disking, and background samples showed
      significant relationships to meteorological parameters (air temperature, relative
      humidity, and dewpoint). Mechanical disturbance by tilling operations reduced the
      ability to predict airborne herbicide concentrations on the basis of
      meteorological conditions. Prometryn concentrations were higher for larger
      particle sizes (Dp > 1.8 MUm), while no clear patterns with particle size were
      observed for trifluralin. Trifluralin concentrations in the smallest size bin
      (PM0.18) were 2-50 times higher than prometryn for the three disking events where
      an impactor was used, indicating the importance of measuring size-resolved
      herbicide distributions in future studies. 

PMID- 24040760
TI  - Deictic gesturing in wild chimpanzees (Pan troglodytes)? Some possible cases.
AB  - Referential pointing is important in the development of language comprehension in
      the child and is often considered a uniquely human capacity. Nonhuman great apes
      do point in captivity, usually for a human audience, but this has been
      interpreted as an interaction pattern learned from human caretakers, not
      indicative of natural deictic ability. In contrast, spontaneous pointing for
      other apes is almost unknown among wild ape populations, supporting doubts as to
      whether apes naturally have any capacity to point referentially. Here the authors
      describe and illustrate 4 cases of gestures by juvenile chimpanzees in the Sonso
      chimpanzee community in Budongo, Uganda, that, at some level, may appear to be
      deictic and referential. The authors discuss the possible reasons why
      chimpanzees, if they possess a capacity for referential pointing, do not use it
      more frequently.

PMID- 24040759
TI  - Stem cells isolated from adipose tissue of obese patients show changes in their
      transcriptomic profile that indicate loss in stemcellness and increased
      commitment to an adipocyte-like phenotype.
AB  - BACKGROUND: The adipose tissue is an endocrine regulator and a risk factor for
      atherosclerosis and cardiovascular disease when by excessive accumulation induces
      obesity. Although the adipose tissue is also a reservoir for stem cells (ASC)
      their function and "stemcellness" has been questioned. Our aim was to investigate
      the mechanisms by which obesity affects subcutaneous white adipose tissue (WAT)
      stem cells. RESULTS: Transcriptomics, in silico analysis, real-time polymerase
      chain reaction (PCR) and western blots were performed on isolated stem cells from
      subcutaneous abdominal WAT of morbidly obese patients (ASCmo) and of non-obese
      individuals (ASCn). ASCmo and ASCn gene expression clustered separately from each
      other. ASCmo showed downregulation of "stemness" genes and upregulation of
      adipogenic and inflammatory genes with respect to ASCn. Moreover, the application
      of bioinformatics and Ingenuity Pathway Analysis (IPA) showed that the
      transcription factor Smad3 was tentatively affected in obese ASCmo. Validation of
      this target confirmed a significantly reduced Smad3 nuclear translocation in the
      isolated ASCmo. CONCLUSIONS: The transcriptomic profile of the stem cells
      reservoir in obese subcutaneous WAT is highly modified with significant changes
      in genes regulating stemcellness, lineage commitment and inflammation. In
      addition to body mass index, cardiovascular risk factor clustering further affect
      the ASC transcriptomic profile inducing loss of multipotency and, hence, capacity
      for tissue repair. In summary, the stem cells in the subcutaneous WAT niche of
      obese patients are already committed to adipocyte differentiation and show an
      upregulated inflammatory gene expression associated to their loss of
      stemcellness.

PMID- 24040761
TI  - The incentive value of males' 50-kHz ultrasonic vocalizations for female rats
      (Rattus norvegicus).
AB  - Rats emit ultrasonic vocalizations (USVs) of 22 kHz and 50 kHz before, during,
      and after copulation. The 50-kHz vocalizations can be subdivided into flat and
      frequency-modulated (FM) trill calls. In this study, the role of 50-kHz USVs in
      sexual incentive motivation in female rats was examined. USVs were recorded from
      sexually active males during the precopulatory phase. In the first two
      experiments, "full 10-min song," flat-call, and FM-trill-call stimuli were used.
      In Experiment 1, a combination of complex and trill calls was used as the FM
      trill call, whereas a mixture of multistep and upward ramp calls was used in
      Experiment 2. The auditory stimuli were played back to sexually receptive female
      rats in a sexual incentive-motivation test. For comparison, the odor of an intact
      male rat was also used as incentive stimulus. The flat-call stimulus did not
      induce approach behavior in any experiment, whereas the FM trill showed a short
      lived effect in Experiment 2. The females approached the "full song" during the
      first minute of stimulus exposure in Experiment 1, but not in Experiment 2. When
      the entire 10-min test period was analyzed, the females in Experiment 1 did not
      approach the full song more than background noise, though they did so in
      Experiment 2. The olfactory stimulus, to the contrary, had a clear incentive
      value in both experiments. In a third experiment, a devocalized male, an intact
      vocalizing male and a female rat were used as incentive stimuli. The females did
      not approach a vocalizing male more than they approached a silent male, showing
      that USVs do not contribute to the male rat's incentive value. Overall, the
      results of the present series of experiments show that the male rat's USVs do not
      have any consistent incentive value for the sexually receptive female rat. This
      sharply contrasts the strong and reliable effect of male odor.

PMID- 24040762
TI  - Knowledge, attitudes and practices of female genital mutilation/cutting among
      health care professionals in The Gambia: a multiethnic study.
AB  - BACKGROUND: Female genital mutilation/cutting (FGM/C) is a harmful traditional
      practice with severe consequences for the health and well-being of girls and
      women. Health care professionals (HCPs) are therefore expected to be aware of how
      to identify and manage these consequences in order to ensure that those affected
      by the practice receive quality health care. Moreover, their integration and
      legitimacy within the communities allow them to play a key role in the prevention
      of the practice. Nevertheless, the perception of HCPs on FGM/C has been barely
      explored in African contexts. This study seeks to contribute to this field of
      knowledge by examining the knowledge, attitudes, and practices regarding FGM/C
      among HCPs working in rural settings in The Gambia. METHODS: A cross-sectional
      descriptive study was designed through a quantitative methodology, following a
      multiethnic approach. A pre-tested questionnaire with open and closed-ended
      questions was created. Forty medical students from the Community-based Medical
      Programme were trained to administer the questionnaire, face to face, at village
      health facilities in rural areas of The Gambia. A final sample of 468 HCPs
      included all nurse cadres and midwives. RESULTS: A significant proportion of
      Gambian HCPs working in rural areas embraced the continuation of FGM/C (42.5%),
      intended to subject their own daughters to it (47.2%), and reported having
      already performed it during their medical practice (7.6%). However, their
      knowledge, attitudes, and practices were shaped by sex and ethnic identity. Women
      showed less approval for continuation of FGM/C and higher endorsement of the
      proposed strategies to prevent it than men. However, it was among ethnic groups
      that differences were more substantial. HCPs belonging to traditionally
      practicing groups were more favourable to the perpetuation and medicalisation of
      FGM/C, suggesting that ethnicity prevails over professional identity.
      CONCLUSIONS: These findings demonstrate an urgent need to build HCP's capacities
      for FGM/C-related complications, through strategies adapted to their specific
      characteristics in terms of sex and ethnicity. A culturally and gender sensitive
      training programme might contribute to social change, promoting the abandonment
      of FGM/C, avoiding medicalisation, and ensuring accurate management of its health
      consequences.

PMID- 24040763
TI  - An acardiac twin with advanced development of the brain: a histologic and
      volumetric study.
AB  - We describe a rare case of an acardiac twin (acardius anceps) with advanced brain
      development. Complete serial sections of the brain were made for microscopic
      observation and volumetric analysis. The cerebral surface showed unusual gyri and
      sulci with absence of the right olfactory bulb. Cortical lamination was almost
      normal, except for the insula where polymicrogyria and leptomeningeal neuroglial
      heterotopia were seen. The latter was also observed in the basal forebrain.
      Partial agenesis of the corpus callosum was noted with a very thick left
      cingulate gyrus. The anterior commissure did not cross the midline. Subcortical
      structures including basal ganglia, diencephalon, and brainstem/cerebellum
      appeared grossly normal, but hypo- or dysplasic changes were observed in some
      regions. The ventricles were enlarged and the left internal carotid artery was
      absent. In addition, porencephalic foci were located in the right temporal and
      parietal lobes. On comparative volumetry, the total brain was normal, but brain
      structures showed variable volumetric changes, with higher volume in the
      ventricles, diencephalon, and archi-/paleopallium, and lower volume in the
      periventricular germinal layer, basal ganglia, cerebral cortex, and
      brainstem/cerebellum. These observations showed that brain development can
      proceed nearly normally in acardia if blood flow is relatively preserved. 

PMID- 24040764
TI  - A switchable intramolecular hydrogen bond in polysubstituted 5
      nitrosopyrimidines.
AB  - The formation of strong intramolecular hydrogen bonds was observed in a series of
      2-amino-5-nitrosopyrimidines with alkylamino and arylamino substituents at
      positions 4 and 6. Mixtures of two rotamers differing in the orientation of the
      nitroso group were observed in the NMR spectra of the compounds where two
      distinct intramolecular hydrogen bonds could be formed. The ratio of the two
      rotamers depends strongly on the character of the substituents at positions 4 and
      6 and can be finely tuned over a broad range of conformation ratios. The
      experimental results were supported by DFT calculations, which also made it
      possible to explain the apparent contradiction in the experimental dependence of
      the rotamer ratio on the Hammett constants for the arylamino substituents. The
      UV/vis spectra of the compounds also significantly depend on the nature of the
      substituents; however, the orientation of the nitroso group does not have any
      influence on the position of the absorption bands in the spectra. 

PMID- 24040765
TI  - Mitochondrial function and apoptosis of peripheral mononuclear cells (PBMCs) in
      the HIV infected patients.
AB  - HIV infection results in the development of immunodeficiency mainly due to the
      apoptosis of infected and by stander CD4 cells. The aim of the study was to
      follow the mitochondrial dependent pathway of apoptosis, one of the suggested
      mechanisms of above process. The inner mitochondrial membrane potential (MMP),
      Adenosine-5'-triphosphate (ATP) generation, apoptosis and necrosis markers of
      peripheral mononuclear cells (PBMCs) were compared in HIV infected patients and
      HIV negative control group. The correlation of blood viral load, TNFalpha
      concentration, CD4 cells count and duration of ARV therapy was considered.
      Additionally, group of HIV infected ARV-naive patients was involved for the
      follow-up study and the effects of one year of ARV therapy on measured parameters
      were studied. PBMCs of HIV infected individuals (especially without ARV therapy)
      demonstrated lower MMP and ATP generation and higher percentage of
      apoptotic/necrotic PBMCs. Correlation between blood TNFalpha level and
      mitochondrial dysfunction was observed. The first months of ARV therapy resulted
      in most significant restoration of mitochondrial function and living PBMCs count.
      HIV infection and ARV therapy have significant impact on mitochondrial function
      and apoptosis of PBMCs. They are driven by abnormal mitochondrial function
      apoptosis of immune cells which seems to be the key element leading to
      immunosuppression, thus an early intervention in this process by therapy can be
      beneficial for symptomatology of HIV infected patients. 

PMID- 24040766
TI  - Apolipoprotein M T-778C polymorphism is associated with serum lipid levels and
      the risk of coronary artery disease in the Chinese population: a meta-analysis.
AB  - BACKGROUND: The apolipoprotein M (APOM) T-778C gene polymorphism has been
      associated with serum lipid levels and the risk of coronary artery disease (CAD),
      but the results are inconclusive. The purpose of this meta-analysis was to detect
      the association between the APOM T-778C polymorphism and serum lipid levels and
      the risk of CAD in the Chinese population. METHODS: Databases of MEDLINE, EMBASE,
      the Cochrane Library and CNKI were systematically searched. Data were extracted
      using standardized methods. The association was assessed by mean difference (MD)
      with 95% confidence intervals (CI) or odds ratio (OR) with 95% CI. RESULTS: Ten
      studies with 4,413 patients were included in this meta-analysis. Pooled effects
      indicated that CT+CC group had higher levels of total cholesterol (TC) (MD:-0.36,
      95% CI: -0.53 - -0.19, P < 0.0001) and low-density lipoprotein cholesterol (LDL
      C) (MD: -0.08, 95% CI: -0.16 - -0.01, P = 0.03) than TT group. There was no
      difference in the levels of triglyceride (MD: 0.06, 95% CI: -0.04 - 0.15, P =
      0.22) and high-density lipoprotein cholesterol (MD: 0.00, 95% CI: -0.03-0.03, P =
      0.93) between TT and CT+CC groups. Pooled effects showed that CAD group had
      higher CT+CC genotype frequency than control group (OR: 1.97, 95% CI: 1.62-2.39,
      P < 0.00001; heterogeneity test x(2) = 2.96, P = 0.71, I(2) = 0%). CONCLUSIONS:
      The results of the current meta-analysis show that the CT+CC group has higher
      levels of TC and LDL-C than the TT group. Moreover, there is also a prominent
      association between APOM T-778C polymorphism and the risk of CAD in the Chinese
      population, the CT+CC genotype is associated with increased risk of CAD.

PMID- 24040767
TI  - Retransfusion of cardiotomy suction blood impairs haemostasis: ex vivo and in
      vivo studies.
AB  - OBJECTIVES: Cardiotomy suction blood in volumes corresponding to 10-20% of the
      systemic blood volume is retransfused during cardiopulmonary bypass. We
      hypothesized that retransfusion of unwashed cardiotomy suction blood influences
      coagulation and platelet function. DESIGN: Systemic blood samples collected
      during cardiopulmonary bypass were supplemented ex vivo with autologous wound
      blood (5, 10 and 20%, respectively). Clot formation and platelet function were
      assessed with thromboelastometry and platelet aggregometry. In an in vivo pilot
      study 30 patients were randomized into a retransfusion and a no-retransfusion
      group. Clot formation, platelet aggregability and thrombin generation capacity
      were compared between the groups. RESULTS: Cardiotomy suction blood had markedly
      impaired clot stability and reduced levels of fibrinogen and platelets compared
      with systemic blood. Ex vivo addition of 10% and 20% suction blood to systemic
      blood impaired platelet aggregability and clot stability. Retransfusion of small
      amounts of wound blood in vivo (mean volume 280 ml, corresponding to 5% of the
      blood volume) did not significantly influence haemostasis. CONCLUSIONS: The ex
      vivo results suggest that addition of unwashed cardiotomy suction blood in
      clinically relevant volumes impairs systemic haemostasis. Retransfusion of
      smaller volumes in vivo has no or limited impact. Avoiding retransfusion of
      larger amounts of unwashed cardiotomy suction may improve postoperative
      haemostasis.

PMID- 24040768
TI  - What is the price of neglecting parasite groups when assessing the cost of co
      infection?
AB  - Although co-infection by multiple groups of pathogens is the norm rather than the
      exception in nature, most research on the effects of pathogens on their hosts has
      been largely based on a single or few pathogen species. Nevertheless, the health
      impact of co-occurring infections is evident, and it is important that scientists
      should consider pathogen communities rather than single relevant pathogen species
      when assessing the impact of multiple infections. In this work we illustrate the
      consequences of neglecting different pathogen taxa (viruses, protozoa, helminths,
      arthropods) in the explanatory power of a set of Partial Least Squares Regression
      (PLS-R) models used for exploring the impact of co-infections on the body
      condition of 57 adult feral cats; 71.5% cats were co-infected by >=3 groups of
      pathogens. The best two PLS-R models provided a first component based on the
      combination of helminths, protozoa and viruses, explaining 29.15% of body
      condition variability. Statistical models, partially considering the pathogen
      community, lost between 24% and 94% of their explanatory power for explaining the
      cost of multiple infections. We believe that in the future, researchers assessing
      the impact of diseases on host life-history traits should take into account a
      broad representation of the pathogen community, especially during early
      assessment of the impact of diseases on host health.

PMID- 24040769
TI  - Lessons learned in multisite, nursing education research while studying a
      technology learning innovation.
AB  - Multiple challenges must be addressed when educational research is being
      conducted that involves a teaching innovation at multiple sites over time,
      including the consistent adoption and use of the intervention, attrition,
      response rates, and other aspects related to managing a complex study. After an
      18-month nursing education study was conducted at multiple institutions across
      the United States, the authors' study team reflected on strategies that worked
      well, the challenges faced, and what could have been done differently. This
      article details the challenges and offers recommendations for other researchers
      conducting similar studies. Recommendations related to communication and
      engagement, innovation fidelity, survey fatigue, multiple institutional review
      board applications, and flexibility are provided.

PMID- 24040770
TI  - Eighty percent by 2020: the present and future of RN-to-BSN education.
AB  - More than 600 RN-to-BSN programs currently exist in the United States, and the
      numbers of programs and students are growing rapidly. This unprecedented growth
      is a result of several factors, including the Institute of Medicine's
      recommendation that 80% of RNs be BSN prepared by 2020. This survey was
      undertaken to explore key ideas and issues related to RN-to-BSN education to
      gather information on how RN-to-BSN programs are changing and to uncover concerns
      posited by program directors. The survey indicated that lack of standardization
      has resulted in significant variability in expectations and requirements among RN
      to-BSN programs. Further, numerous questions need to be answered and concerns
      addressed to develop strategies to maintain growth, improve access, and remove
      barriers without sacrificing quality. Findings can be used to ensure that RN-to
      BSN education prepares graduates for the future health care system and that the
      outcome is not just a piece of paper.

PMID- 24040771
TI  - Teaching about vulnerable populations: nursing students' experience in a homeless
      center.
AB  - Cultural competence is not limited to ethnicity, religion, or race but is
      inclusive of vulnerable groups, such as the homeless. The complex health and
      social issues related to homelessness requires educational instruction that
      supports students' ability to address and care for the multidimensional elements
      that surround this group. Exposure to homeless populations provides nursing
      students with increased awareness of the issues related to health disparities,
      while promoting introspective reflection on one's values and beliefs. To increase
      student exposure to working with homeless clients, a service-learning project
      using a critical social theory (CST) lens was offered at a homeless center. The
      students' response that clients were "just like" them, coupled with ambiguity
      regarding the complex social-economic-political issues surrounding the homeless,
      may indicate a need for further education regarding cultural understanding,
      sensitivity, and vulnerability. This project demonstrates the need for learning
      experiences that support advocacy and social responsibility for vulnerable
      groups.

PMID- 24040772
TI  - Novice nurse educator entry-level competency to teach: a national study.
AB  - Expert nurse clinicians who are transitioning into academic positions after
      successful clinical careers often find they are unprepared to assume their new
      educator roles. Although nursing clinical expertise may be a necessary
      expectation, this knowledge is not sufficient to assume a nurse educator
      position. The purpose of this study was to identify essential entry-level nurse
      educator competencies, as reported by nurse administrators of accredited
      prelicensure nursing programs in the United States. Responses were categorized
      according to the type of academic institution housing the prelicensure nursing
      program and type of entry-level nurse educator position. A total of 374 program
      administrators representing 48 states participated, for a 44% response rate. The
      results indicate that administrators expect entry-level nurse educators to
      acquire teaching competencies prior to obtaining an entry-level position.
      Expected proficiency levels of competencies differed based on the position type
      and the academic setting.

PMID- 24040773
TI  - Development of chitosan-crosslinked nanofibrous PHBV guide for repair of nerve
      defects.
AB  - The aim of this study was to produce a chitosan-crosslinked nanofibrous
      biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nerve conduit.
      The artificial scaffold was designed by electrospinning method, and cross-linked
      with chitosan by chemical method. The scaffolds were evaluated by microscopic,
      physical, and mechanical analyses, and cell culture assays with Schwann cells.
      Results of analyses showed a good resilience and compliance with movement as a
      neural graft. Cellular experiments showed a better cell adhesion and growth
      inside the crosslinked nanofibrous scaffolds compared with un-crosslinked ones.
      This neural conduit appears to have the right organization for testing in vivo
      nerve tissue engineering studies.

PMID- 24040774
TI  - IL-17 producing T cells in celiac disease: angels or devils?
AB  - Celiac disease (CD) is a very common chronic condition in human beings, affecting
      approximately one in 100 individuals. It is an autoimmune disease with a defined
      environmental trigger, the gluten contained in dietary cereals, occurring in
      genetically susceptible individuals. The disease has a very strong HLA
      association. More than 90% of CD patients have HLA-DQ2, and almost all of the
      remaining celiac population possesses HLA-DQ8 molecules. Th17 cells seem to
      participate in the disease pathogenesis producing and secreting either
      proinflammatory or anti-inflammatory cytokines. 

PMID- 24040775
TI  - Induced vertical disparity effects on local and global stereopsis.
AB  - PURPOSE: Although significant amounts of vertical misalignment could have a
      noticeable effect on visual performance, there is no conclusive evidence about
      the effect of very small amount of vertical disparity on stereopsis and binocular
      vision. Hence, the aim of this study was to investigate the effects of induced
      vertical disparity on local and global stereopsis at near. MATERIALS AND METHODS:
      Ninety participants wearing best-corrected refraction had local and global
      stereopsis tested with 0.5 and 1.0 prism diopter (Delta) vertical prism in front
      of their dominant and non-dominant eye in turn. This was compared to local and
      global stereopsis in the same subjects without vertical prism. Data were analyzed
      in SPSS.17 software using the independent samples T and the repeated measures
      ANOVA tests. RESULTS: Induced vertical disparity decreases local and global
      stereopsis. This reduction is greater when vertical disparity is induced in front
      of the non-dominant eye and affects global more than local stereopsis. Repeated
      measures ANOVA showed differences in the mean stereopsis between the different
      measured states for local and global values. Local stereopsis thresholds were
      reduced by 10 s of arc or less on average with 1.0Delta of induced vertical prism
      in front of either eye. However, global stereopsis thresholds were reduced by
      over 100 s of arc by the same 1.0Delta of induced vertical prism. CONCLUSION:
      Induced vertical disparity affects global stereopsis thresholds by an order of
      magnitude (or a factor of 10) more than local stereopsis. Hence, using a test
      that measures global stereopsis such as the TNO is more sensitive to vertical
      misalignment than a test such as the Stereofly that measures local stereopsis.

PMID- 24040776
TI  - Response to 'EBM and gut feelings'.

PMID- 24040777
TI  - Perfectionism, emotion regulation, and the cortisol stress response.
AB  - To provide counseling psychologists with a greater understanding of patterns of
      personality, stress, and emotion regulation, the present study examined
      perfectionists' typical emotion regulation patterns and physiological reactivity
      (salivary cortisol concentration) to a social-evaluative stress experience. An
      initially large sample (N = 421) completed measures of perfectionism, higher
      order personality factors, and emotion regulation. A subset of the larger sample
      (N = 61) completed the Trier Social Stress Test. Latent profile analysis revealed
      typologies consistent with more and less adaptively perfectionistic groups, as
      reflected in different stress reactivity and emotion regulation patterns. The
      results have implications for further understanding the positive and negative
      effects of perfectionism and physiological reactivity to performance stress among
      individuals with high performance expectations. In addition, the results may
      inform counseling psychologists about viable targets for therapeutic
      interventions for stress and emotion regulation.

PMID- 24040778
TI  - Face consciousness among South Korean women: a culture-specific extension of
      objectification theory.
AB  - This study tested key tenets of objectification theory with South Korean women
      and explored the roles of sexually objectifying media and culture-specific
      standards of beauty in body image and eating disorder symptoms. Two pilot studies
      with South Korean college women (n = 40, n = 30) revealed that facial
      characteristics such as size and shape represent a discrete variable among
      culture-specific standards of beauty for South Korean women. Results with a
      sample of 562 South Korean college women indicated that media exposure had
      significant positive indirect relations with body shame and eating disorder
      symptoms through the mediating roles of internalization, body surveillance, and
      face surveillance. Internalization of cultural standards of beauty had
      significant positive direct relations with body surveillance and face
      surveillance and had both direct and indirect relations with body shame and
      eating disorder symptoms. Body and face surveillances had significant positive
      direct relations with body shame and had indirect relations with eating disorder
      symptoms. Finally, body shame mediated the links from internalization and
      surveillance variables to eating disorder symptoms. The results support the
      applicability of objectification theory as it relates to South Korean women and
      point to the significance of culture-specific standards of beauty within that
      framework. These findings could contribute to the broader field of multicultural
      body image research, with potential implications for therapist practices and
      training. (PsycINFO Database Record (c) 2014 APA, all rights reserved). 

PMID- 24040779
TI  - Evolutionary history of Ebola virus.
AB  - SUMMARY: Since Ebola virus was discovered in 1970s, the virus has persisted in
      Africa and sporadic fatal outbreaks in humans and non-human primates have been
      reported. However, the evolutionary history of Ebola virus remains unclear. In
      this study, 27 Ebola virus strains with complete glycoprotein genes, including
      five species (Zaire, Sudan, Reston, Tai Forest, Bundibugyo), were analysed. Here,
      we propose a hypothesis of the evolutionary history of Ebola virus which will be
      helpful to investigate the molecular evolution of these viruses.

PMID- 24040780
TI  - Pericytes and renal microvascular disease induce renal fibrosis in CKD.

PMID- 24040781
TI  - An unexpected diagnosis in a renal-transplant patient with proteinuria treated
      with everolimus: AL amyloidosis.
AB  - Proteinuria is an expected complication in transplant patients treated with
      mammalian target of rapamycin inhibitors (mTOR-i). However, clinical suspicion
      should always be supported by histological evidence in order to investigate
      potential alternate diagnoses such as acute or chronic rejection, interstitial
      fibrosis and tubular atrophy, or recurrent or de novo glomerulopathy. In this
      case we report the unexpected diagnosis of amyloidosis in a renal-transplant
      patient with pre-transplant monoclonal gammapathy of undetermined significance
      who developed proteinuria after conversion from tacrolimus to everolimus. 

PMID- 24040782
TI  - Mycoplasma edwardii peritonitis in a patient on maintenance peritoneal dialysis.
AB  - Mycoplasma edwardii (M. edwardii) is an anthropozoonotic microorganism found in
      the upper respiratory and urogenital tracts of dogs. M. edwardii was one of the
      microbes isolated from peritoneal fluid of a 10-year-old child diagnosed with
      polymicrobial peritonitis following a puncture of dialysis tubing by a pet dog.
      Other unique pathogens representative of canine oral microflora isolated from
      this patient on peritoneal dialysis were Kingella denitrificans, Actinomycetes
      species and Capnocytophaga cynodegmi. 

PMID- 24040783
TI  - Urinary KIM-1, IL-18 and Cys-c as early predictive biomarkers in gadolinium-based
      contrast-induced nephropathy in the elderly patients.
AB  - BACKGROUND/AIMS: This study was designed to investigate whether urinary kidney
      injury molecule-1 (KIM-1), interleukin-18 (IL-18) and cystatin C (Cys-C) are
      early predictive biomarkers for gadolinium-based contrast-induced nephropathy (Gd
      CIN) in the elderly patients undergoing gadolinium-enhanced magnetic resonance
      imaging (MRI). METHODS: 60 elderly patients undergoing enhanced MRI using
      gadolinium-based contrast media were enrolled. Urine samples were collected
      before and 24 hours and 48 hours after the procedure, and KIM-1, IL-18 and Cys-C
      levels were measured by using an ELLSA kit respectively. Serum samples before and
      24 hours and 48 hours after the procedure were also collected, and creatinine was
      measured by automatic biochemical analyzer. RESULTS: Gd-CIN was diagnosed in 8 of
      60 (13.3%) patients. At 24 hours after MRI with gadolinium administration in the
      Gd-CIN group, the urinary KIM-1, IL-18 and Cys-C were significantly increased.
      Logistic regression analysis showed that urinary KIM-1 and IL-18 at 24 hours
      after gadolinium injection were independent predictive markers of Gd-CIN. The
      predictable time of acute kidney injury (AKI) onset determined by urinary KIM-1,
      IL-18 and Cys-C was 24 hours earlier than by serum creatinine. CONCLUSIONS:
      Urinary KIM-1, IL-18 and Cys-C could be early predictive biomarkers of Gd-CIN in
      the elderly patients, which showed a good performance in early diagnosis of Gd
      CIN as compared with serum creatinine.

PMID- 24040784
TI  - Toward a "molecular thermometer" to estimate the charring temperature of wildland
      charcoals derived from different biomass sources.
AB  - The maximum temperature experienced by biomass during combustion has a strong
      effect on chemical properties of the resulting charcoal, such as sorption
      capacity (water and nonpolar materials) and microbial degradability. However,
      information about the formation temperature of natural charcoal can be difficult
      to obtain in ecosystems that are not instrumented prior to fires. Benzene
      polycarboxylic acids (BPCA) are molecular markers specific for pyrogenic carbon
      (PyC) which can provide information on the degree of aromatic condensation in
      charcoals. Here we apply the BPCA molecular marker method to a set of 10
      charcoals produced during an experimental fire in a Pitch pine-scrub oak forest
      from litter and bark of pitch pine and inkberry plants in the Pinelands National
      Reserve in New Jersey, USA. We deployed temperature-sensitive crayons throughout
      the burn site, which recorded the maximum air temperature and made comparisons to
      the degree of thermal alteration recorded by BPCA molecular markers. Our results
      show an increase of the degree of aromatic condensation with monitored
      temperatures for bark biomass, while for needles no clear trend could be
      observed. For leaf-derived charcoals at increasing monitored fire temperatures,
      decreasing degree of aromatic condensation was obtained. This suggests that
      molecular markers can be used to roughly estimate the maximum fire temperatures
      experienced by bark and wood materials, but not based on leaf- and needle-derived
      materials. Possible applications include verifying declared pyrolysis
      temperatures of biochars and evaluating ecosystem fire temperature postburn. 

PMID- 24040785
TI  - Explorations of a series of second order nonlinear optical materials based on
      monovalent metal gold(III) iodates.
AB  - The syntheses, crystal structures, and characterizations of a series of
      monovalent metal gold(III) iodates, namely, alpha-NaAu(IO3)4, beta-NaAu(IO3)4,
      RbAu(IO3)4, alpha-CsAu(IO3)4, beta-CsAu(IO3)4, and AgAu(IO3)4 are reported. Their
      structures feature Au(IO3)4(-) anions that are separated by alkali metal ions or
      silver(I) ions. The Au(IO3)4(-) anions in the polar alpha-NaAu(IO3)4, RbAu(IO3)4,
      and alpha-CsAu(IO3)4 are polar with all four iodate groups being located only
      above (or below) the AuO4 square plane (cis- configuration). alpha-NaAu(IO3)4,
      RbAu(IO3)4, and alpha-CsAu(IO3)4 display moderate strong Second-Hamonic
      Generation (SHG) responses of 1.17 *, 1.33 *, and 1.17 * KTP (KTiOPO4),
      respectively, and all three materials are type-I phase-matchable. The Au(IO3)4(-)
      anions in centrysymmetric beta-NaAu(IO3)4, beta-CsAu(IO3)4, and AgAu(IO3)4 are
      nonpolar with the four iodate groups of the Au(IO3)4(-) anion being located both
      above and below the AuO4 square plane (trans- configuration). IR and UV spectra,
      luminescent and ferroelectric properties have also been measured. Theoretical
      calculations of their optical properties based on density functional theory (DFT)
      methods were performed by using the CASTEP total-energy code. 

PMID- 24040786
TI  - Multicompartmental Janus microbeads from branched polymers by single-emulsion
      droplet microfluidics.
AB  - We describe a versatile and facile route for the preparation of Janus microbeads
      using single emulsion droplet-based microfluidics, in which water droplets that
      contain a mixture of branched poly(N-isopropylacrylamide)-co-(poly(ethylene
      glycol)diacrylate)-co-(methacrylic acid) and colloidal particles form the basis
      of our approach. The colloidal particles, poly(methyl methacrylate) microspheres
      or titanium dioxide particles, and iron oxide nanoparticles are spatially
      positioned within the water droplets through gravity and an externally applied
      magnetic force, respectively. Evaporation of water leads to gel formation of the
      branched copolymer matrix as a result of physical cross-linking through hydrogen
      bond interactions, fixing the spatial position of the colloidal particles. The
      thermo- and pH-responsive nature of the branched poly(N-isopropylacrylamide)
      (PNIPAm)-based copolymer allows for the disintegration of the polymer network of
      the Janus microbeads and a triggered release of the colloidal content at
      temperatures below the lower critical solution temperature (LCST) and at
      increased pH values. 

PMID- 24040787
TI  - Do folate, vitamins B6 and B12 play a role in the pathogenesis of migraine? The
      role of pharmacoepigenomics.
AB  - Migraine is a neurovascular disease that has classically been attributed to
      multifactorial aetiologies, with genetic components and environmental
      interactions considered the main influence. Genes such as flavoenzyme 5, 10-
      methylenetetrahydrofolate reductase (MTHFR), especially the C677T variant, have
      been associated with elevated plasma homocysteine levels. This elevation in
      homocysteine results in an array of metabolic disorders and increased risk of
      complex diseases, including migraine. Catalysation of homocysteine requires the
      presence of vitamins B6, B12 and folate. Deficiencies in these cofactor vitamins
      result in hypomethylation, which triggers migraine. Because migraine
      predominantly affects females, it is hypothesised that fluctuating oestrogen
      levels, which are governed by oestrogen receptor 1 polymorphisms, are important.
      Another important factor is homocysteine, the production of which is dependent
      upon MTHFR and B vitamins. Gene expression is modulated through epigenetic
      mechanisms, which involve methionine. Additionally, folate plays a major role in
      DNA synthesis. We propose that vitamin B intake, coupled with MTHFR and oestrogen
      receptor 1 polymorphisms, causes differential DNA methylation and gene expression
      that may contribute to the occurrence of migraine. 

PMID- 24040788
TI  - Blockade of MK-801-induced heat shock protein 72/73 in rat brain by antipsychotic
      and monoaminergic agents targeting D2, 5-HT1A, 5-HT2A and alpha1-adrenergic
      receptors.
AB  - Noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists can produce
      positive and negative symptomatology as well as impairment of cognitive function
      that closely resemble those present in schizophrenia. In rats, these drugs induce
      a behavioral syndrome (characterized by hyperlocomotion and stereotypies), an
      enhanced glutamatergic transmission in the medial prefrontal cortex, and damage
      to retrosplenial cortical neurons in adult rats, which was measured as the
      induction of the stress protein 72/73 kDa heat shock protein (Hsp72/73). In the
      present work, we have examined the existence of possible differences among
      different antipsychotic drugs in their capacity to block immunolabeling of
      Hsp72/73 in the retrosplenial cortex of the rat induced by the potent NMDA
      receptor antagonist, MK- 801. In addition, the effects of selective monoaminergic
      agents were also studied to delineate the particular receptors responsible for
      the actions of antipsychotic drugs. Pretreatment with clozapine, chlorpromazine,
      olanzapine, ziprasidone--and to a lesser extent haloperidol-reduced the formation
      of Hsp72/73 protein in the rat retrosplenial cortex after the administration of
      MK-801. In addition, antagonism at dopamine D2 (raclopride), 5-HT2 (M100907) and
      alpha1- adrenoceptors (prazosin) as well as agonism at 5-HT1A receptors (BAY x
      3702) also diminished the MK-801-induced number of cells labeled with Hsp72/73.
      Each of these effects may contribute to antipsychotic action. The results suggest
      that the efficacy of atypical antipsychotic drugs in the clinic may result from a
      combined effect on 5-HT2, 5-HT1A and alpha1-adrenergic receptors added to the
      classical dopamine D2 receptor antagonism.

PMID- 24040789
TI  - Highly organized nanostructures for brain drug delivery--new hope or just a fad?
AB  - The blood-brain barrier significantly impedes treatment of central nervous system
      disorders by preventing drug entry into the brain. Several strategies have been
      developed to overcome this problem, but progress has been hampered due to a lack
      of efficacious drug delivery systems (DDS). Now, owing to DDS, therapeutic
      compounds can be transported to the site of action and accumulate there. This
      modern approach allows one to decrease the required dose of drug and, therefore,
      minimize toxicity and side effects. Also, treatment efficiency is increased.
      Highly organized nanostructures made of biological, polymeric or carbon-based
      materials are promising carriers in drug delivery to the brain, due to their
      unique and easily tailorable properties. The drug can be either attached to or
      entrapped in a carrier. To achieve greater site specificity and selectivity, DDS
      can be also modified with suitable ligands, providing identification of the
      molecular site of action. This review illustrates recent advances in using highly
      organized structures: dendrimers, fullerenes, liposomes, micelles, nanogels,
      nanoparticles and nanotubes for this purpose. We also discuss advantages and
      limitations of each system. 

PMID- 24040791
TI  - Cerebrovascular profile assessment in Parkinson's disease patients.
AB  - INTRODUCTION: Parkinson's disease (PD) is one of the most common
      neurodegenerative diseases, and PD patients can present a variety of
      comorbidities that increase with age. Among them, cardiovascular and
      cerebrovascular diseases are the most prominent. AIM: To assess the
      cardiovascular and cerebrovascular profiles of PD patients. PATIENTS AND METHODS:
      The cardiovascular risk factors of 126 PD patients were assessed according to
      laboratory tests (fasting blood sugar, serum cholesterol, triglycerides, and
      total lipids), Doppler ultrasound examinations and personal histories of
      cerebrovascular disease (ischemic/hemorrhagic), cardiovascular disease
      (myocardial infarct or angina confirmed by electrocardiogram), hypertension and
      diabetes. All patients underwent cerebral structural imaging procedures: computed
      tomography or magnetic resonance imaging. RESULTS: 58.73% of the patients
      presented with hypertension, with a slight predominance of female patients
      (65.38% vs 47.92%, P = 0.05). Carotid or vertebral atheromatosis was present in
      39 (30.95%) and 28 (22.22%) of patients, respectively, and was statistically
      correlated with the presence of ischemic lesions on cerebral imaging. Regarding
      the computed tomography findings, 33 patients (28.21%) presented with cortical
      atrophy that was not correlated with any of the investigated cardiovascular
      factors. CONCLUSIONS: Our findings indicate that risk factors for cardiovascular
      and cerebrovascular diseases are common in PD patients, possibly due to their
      older age. The presence of atherosclerosis and its complications can be detected
      in cerebral imaging studies.

PMID- 24040792
TI  - Effects of brain IKKbeta gene silencing by small interfering RNA on P
      glycoprotein expression and brain damage in the rat kainic acid-induced seizure
      model.
AB  - Multidrug resistance mediated by over-expression of P-glycoprotein (P-gp) in
      brain is an important mechanism accounting for the drug-therapy failure in
      epilepsy. Over-expression of P-gp in epilepsy rat brain may be regulated by
      inflammation and nuclear factor-kappa B (NF-kappaB) activation. Inhibitory kappa
      B kinase subunit beta (IKKbeta) is an up-stream molecular controlling NF-kappaB
      activation. With the small interfering RNA (siRNA) technique and kainic acid (KA)
      induced rat epileptic seizure model, the present study was aimed to further
      evaluate the role of NF-kappaB inhibition, via blocking IKKbeta gene
      transcription, in the epileptic brain P-gp over-expression, seizure
      susceptibility, and post-seizure brain damage. siRNA targeting IKKbeta was
      administered to rats via intracerebroventricular injection before seizure
      induction by KA microinjection; scrambled siRNA was used as control. Brain mRNA
      and protein levels of IKKbeta and P-gp were detected by RT-PCR and
      immunohistochemistry. NF-kappaB activity was measured by electrophoretic mobility
      shift assay. Latency to grade III or V seizure onset was recorded, brain damage
      was evaluated by neuronal cell counting and epileptiform activity was monitored
      by electroencephalography. IKKbeta siRNA pre-treatment inhibited NF-kappaB
      activation and abolished P-gp over-expression in KA-induced epileptic rat brain,
      accompanied by decreased seizure susceptibility. These findings suggested that
      epileptogenic-induced P-gp over-expression could be regulated by IKKbeta through
      the NF-kappaB pathway.

PMID- 24040793
TI  - Computational analysis of TRAPPC9: candidate gene for autosomal recessive non
      syndromic mental retardation.
AB  - Mental retardation (MR)/ intellectual disability (ID) is a neuro-developmental
      disorder characterized by a low intellectual quotient (IQ) and deficits in
      adaptive behavior related to everyday life tasks such as delayed language
      acquisition, social skills or self-help skills with onset before age 18. To date,
      a few genes (PRSS12, CRBN, CC2D1A, GRIK2, TUSC3, TRAPPC9, TECR, ST3GAL3, MED23,
      MAN1B1, NSUN1) for autosomal-recessive forms of non syndromic MR (NS-ARMR) have
      been identified and established in various families with ID. The recently
      reported candidate gene TRAPPC9 was selected for computational analysis to
      explore its potentially important role in pathology as it is the only gene for ID
      reported in more than five different familial cases worldwide. YASARA (12.4.1)
      was utilized to generate three dimensional structures of the candidate gene
      TRAPPC9. Hybrid structure prediction was employed. Crystal Structure of a
      Conserved Metalloprotein From Bacillus Cereus (3D19-C) was selected as best
      suitable template using position-specific iteration-BLAST. Template (3D19-C)
      parameters were based on E-value, Z-score and resolution and quality score of
      0.32, -1.152, 2.30 degrees A and 0.684 respectively. Model reliability showed
      93.1% residues placed in the most favored region with 96.684 quality factor, and
      overall 0.20 G-factor (dihedrals 0.06 and covalent 0.39 respectively). Protein
      Protein docking analysis demonstrated that TRAPPC9 showed strong interactions of
      the amino acid residues S(253), S(251), Y(256), G(243), D(131) with R(105),
      Q(425), W(226), N(255), S(233), its functional partner 1KBKB. Protein-protein
      interacting residues could facilitate the exploration of structural and
      functional outcomes of wild type and mutated TRAPCC9 protein. Actively involved
      residues can be used to elucidate the binding properties of the protein, and to
      develop drug therapy for NS-ARMR patients.

PMID- 24040794
TI  - Total bakkenolides protects neurons against cerebral ischemic injury through
      inhibition of nuclear factor-kappaB activation.
AB  - Total bakkenolides is the major component of the rhizome of Petasites trichinous
      Franch.. In this study, we investigated its neuroprotective effects in a rat
      transient focal cerebral ischemia-reperfusion model, and in an in vitro cerebral
      ischemia model, oxygen-glucose deprivation of cultured nerve cells. Oral
      administration of total bakkenolides immediately after reperfusion at doses of 5,
      10 and 20 mg/kg markedly reduced brain infarct volume and neurological deficits.
      Total bakkenolides significantly attenuated cell death and apoptosis in primarily
      cultured neurons subject to 1-h hypoxia followed by 24-h reoxygenation.
      Morphologic observations directly confirmed its protective effect on neurons. We
      also demonstrated that total bakkenolides could inhibit nuclear factor-kappaB (NF
      kappaB) activation by blocking the classic activation pathway through suppression
      of phosphorylation of IkappaB-kinase complex, NF-kappaB/p65 and inhibitor protein
      IkappaB, inducing nuclear translocation of NF-kappaB/p65 and degradation of
      IkappaB. Further, total bakkenolides inhibited the activation of Akt and the
      extracellular signal-regulated kinase 1/2, two important upstream activators of
      NF-kappaB. In conclusion, our results provide a strong pharmacological basis for
      further understanding the potential therapeutic role of total bakkenolides in
      cerebral ischemic disease and shed new light on its neuroprotective mechanism.

PMID- 24040795
TI  - Searching for disease-modifying drugs in AD: can we combine neuropsychological
      tools with biological markers?
AB  - Drug discovery efforts in Alzheimer's disease (AD) have been directed in the last
      ten years to develop "disease-modifying drugs" able to exert neuroprotective
      effects in an early phase of AD pathogenesis. Unfortunately several candidate
      disease-modifying drugs have failed in Phase III clinical trials conducted in
      mild to moderate AD for different methodological difficulties, such as the time
      course of treatment in relation to development of disease as well as the
      appropriate use of validated biological and neuropsychological markers. Mild
      cognitive impairment (MCI) has been considered a precursor of AD. Much effort is
      now directed to identify the most appropriate and sensitive markers which can
      predict the progression from MCI to AD, such as neuroimaging markers (e.g.
      hippocampal atrophy and amyloid positron emission tomography imaging),
      cerebrospinal fluid markers (i.e. association of elevated tau with low levels of
      amyloid beta -peptide(1-42) and neuropsychological markers (i.e. episodic memory
      deficits and executive dysfunction). Recent studies demonstrate that the
      combination of these different biomarkers significantly increases the chance to
      predict the conversion into AD within 24 months. These biomarkers will be
      essential in the future to analyze clinical efficacy of disease-modifying drugs
      in MCI patients at high risk to develop AD. In the present review we analyze
      recent evidence on the combination of neuropsychological and biological markers
      in AD as a new tool to track disease progression in early AD as well as the
      response to disease-modifying drugs. 

PMID- 24040796
TI  - Anxiety: a systematic review of neurobiology, traditional pharmaceuticals and
      novel alternatives from medicinal plants.
AB  - Pathologic anxiety is a disproportional reaction of individuals to anticipation
      or misinterpretation of a potential danger, which affects individual social and
      personal life. Despite the advances already accomplished, further studies are
      still necessary in order to understand the mechanisms involved in anxiety. These
      may provide more effective and safer treatments to aid in the control of anxiety
      and improve patient quality of life. In this work, we review the current issue
      about anxiety disorders, covering general aspects such as basic epidemiology and
      classification, an overview of the pharmacological treatments employed and the
      current search for natural anxiolytics. Also, a compilation of data investigating
      the neurobiology that underlies anxiety disorders and a brief discussion evolving
      the most usual animal experimental models to study anxiety is presented. 

PMID- 24040797
TI  - Commentary: Never underestimate the power of adenosine in multiple sclerosis.

PMID- 24040798
TI  - Another step towards a neurobiology of suicide.

PMID- 24040799
TI  - Possible impact of microglial cells and the monocyte-macrophage system on
      suicidal behavior.
AB  - Immune dysfunction, including monocytosis, increased blood levels of interleukin
      1 (IL-1), interleukin-6 (IL- 6) and tumor necrosis factor-alpha (TNF-alpha), as
      well as an increased microglial density in certain brain areas, have been
      described in schizophrenia and depression. Interestingly, similar immune
      alterations have been observed in suicide patients regardless of their underlying
      psychiatric diagnosis. This review summarizes relevant data from previous studies
      that have examined peripheral blood, cerebrospinal fluid and human brains (using
      postmortem histology and in vivo positron emission tomography) to investigate
      immune mechanisms in suicidal patients. We discuss whether the observed findings
      indicate that microgliosis and monocyte-macrophage system activation may be a
      useful marker of disease acuity/severity or whether they instead indicate a
      distinct neurobiology of suicide. Notably, pathophysiological mechanisms could
      change during the long-term course of psychiatric diseases. Therefore, different
      patterns of immune activation may be observed when comparing newly diseased
      patients with those who are chronically ill. 

PMID- 24040800
TI  - Hypothalamic pituitary adrenal axis and prolactin abnormalities in suicidal
      behavior.
AB  - Hypothalamic-Pituitary-Adrenal (HPA) axis hyperactivity measured with the
      dexamethasone suppression test and the dexamethesone/CRH test may have some
      predictive power for suicidal behavior in patients with mood disorders. Increased
      prolactin (PRL) levels may be related both to physiological and pathological
      conditions. HPA-axis abnormalities and increased levels of PRL may coexist, and
      common neuroendocrine changes may activate both HPA axis and PRL release. HPA
      axis hyperactivity is presumably present in a large subpopulation of depressed
      subjects. Suicidal behavior is considered to be a form of inward-directed
      aggression, and aggressive behavior has been connected to high androgen levels.
      However, lower plasma total testosterone levels have also been reported in
      subjects with depression and higher suicidality. Lipid/immune dysregulations, the
      increased ratio of blood fatty acids, and increased PRL levels may each be
      associated with the increased production of pro-inflammatory cytokines, which
      have been reported in patients with major depression and patients engaging in
      suicidal behavior. Although no studies have been done to determine whether ante
      mortem physical stress may be detected by raised post-mortem PRL, this would be
      of great interest for physicians. 

PMID- 24040801
TI  - Signal transduction abnormalities in suicide: focus on phosphoinositide signaling
      system.
AB  - Suicide is a major public health concern and each year about one million people
      die by suicide worldwide. Recent studies suggest that suicide may be associated
      with specific neurobiological abnormalities. Earlier studies of neurobiology of
      suicide focused on abnormalities of the serotonergic mechanism. These studies
      suggested that some serotonin receptor subtypes may be abnormal in the postmortem
      brain of suicide victims. Since these receptors are linked to signal transduction
      pathways, abnormalities of signaling mechanisms have been recently studied in the
      postmortem brain of suicide victims. Of particular interest is the 5
      hydroxytryptamine2A receptor-linked phosphoinositide signaling system. Several
      studies have focused on the abnormalities on the component of this signaling
      system and these studies suggest the abnormalities of G proteins, the effectors
      phospholipase C and the second or the third messenger systems, such as protein
      kinase A. Further studies revealed abnormalities in the downstream transcription
      factors such as the cyclic AMP response element binding protein and some of the
      targeted genes of these transcription factors. The most important gene in this
      aspect which has been studied in the suicide is the brain-derived neurotrophic
      factor. Here we critically review the studies focusing on these components of the
      phosphoinositide signaling system in the postmortem brain of both adult and
      teenage suicide victims. These studies provide a better understanding of the
      signal transduction abnormalities in suicide focusing on the phosphoinositide
      signaling pathway. These studies may lead to new therapeutic agents targeting
      specific sites in this signaling cascade. 

PMID- 24040802
TI  - Risk factors for suicide--an alternative view.
AB  - During the past years suicide statistics in Germany showed a dramatic decrease of
      suicide rates. Such a reduction in a comparatively short time period is not
      explainable by an altered frequency of major psychiatric disorders or certain
      neurobiological conditions that may underlie suicide; other factors causing or
      leading to suicide and their modification have to be considered. This overview
      illustrates various risk factors for suicide different from neurobiology.
      Epidemiological aspects and the effect of political, social and economic
      contributions to suicide rates are exemplified. With regard to the incidence of
      major psychiatric disorders the paper focuses on physical illnesses and their
      risk of suicide. Finally the significance of changes in the accessibility of
      suicide methods is discussed. 

PMID- 24040804
TI  - Postmortem-assessed impairment of neuronal activity in depression: the dominant
      impact of suicide.
AB  - We report recent postmortem findings from the Magdeburg Brain Bank related to the
      evaluation of impaired activity of neuronal networks relevant for depression.
      Chronic changes in ribosomal DNA transcriptional activity have been revealed by
      the quantitative evaluation of silver-stained nucleolar organising regions
      (AgNORs). Abnormalities in AgNOR parameters have been found in neurons of the
      prefrontal limbic regions, the amygdala, the external globus pallidus, and the
      serotonergic dorsal raphe nucleus (DRN). The impact of the processes leading to
      suicide has been clearly accentuated in opposition to the weak influence of
      unipolar-bipolar dichotomy, which was only revealed in one area (the anterior
      cingulate cortex). The impact of suicide was most pronounced in the DRN. Our
      AgNOR studies show that the influence of psychotropic medication (antidepressants
      and typical neuroleptics, among others) is limited in the prevention of abnormal
      neuronal activity specific for suicide. 

PMID- 24040803
TI  - Suicide and the polyamine system.
AB  - Suicide is a significant worldwide public health problem. Understanding the
      neurobiology is important as it can help us to better elucidate underlying
      etiological factors and provide opportunities for intervention. In recent years,
      many lines of research have suggested that the polyamine system may be
      dysregulated in suicidal behaviors. Initial research in animals provided evidence
      of a dysfunctional polyamine stress response system, while later work using post
      mortem human brain tissue has suggested that molecular mechanisms may be at play
      in the suicide brain. In this review, we will describe the research that suggests
      the presence of alterations in the polyamine system in mental disorders and
      behavioral phenotypes, with particular attention to work on suicide. In addition,
      we will also describe potential avenues for future work. 

PMID- 24040805
TI  - The role of neuroimaging in our understanding of the suicidal brain.
AB  - This paper provides a review of the literature on neuroimaging studies of
      suicidal behaviour, and discusses the relevance of these studies for our
      understanding of suicidal behaviour. Main findings from molecular imaging studies
      include a reduced prefrontal perfusion or metabolism and a blunted increase in
      activation when challenged in association with a history of suicide attempts.
      Moreover, impairment of the prefrontal serotonergic system in association with
      suicidal behaviour is demonstrated in a number of studies. Recent structural and
      functional imaging studies show changes in cortical and subcortical areas and
      their connections. A number of methodological issues hamper the interpretation of
      findings. Nevertheless, when findings from studies using divergent techniques are
      taken together there is increasing evidence of the involvement of a fronto
      cingulo-striatal network in suicidal behaviour. This involvement is supported
      additionally by findings from neuropsychological studies, which demonstrate
      changes in decision-making processes in association with suicidal behaviour that
      rely on the same network. Further study is needed to translate the increasing
      knowledge from neuroimaging studies in clinical tools for the prediction and
      prevention of suicidal behaviour. 

PMID- 24040806
TI  - Volumetric analysis of the hypothalamus, amygdala and hippocampus in non-suicidal
      and suicidal mood disorder patients--a post-mortem study.
AB  - In recent years, the hypothalamus, amygdala and hippocampus have attracted
      increased interest with regard to the effects of stress on neurobiological
      systems in individuals with depression and suicidal behaviour. A large body of
      evidence indicates that these subcortical regions are involved in the
      pathogenetic mechanisms of mood disorders and suicide. The current neuroimaging
      techniques inadequately resolve the structural components of small and complex
      brain structures. In previous studies, our group was able to demonstrate a
      structural and neuronal pathology in mood disorders. However, the impact of
      suicide remains unclear. In the current study we used volumetric measurements of
      serial postmortem sections with combined Nissl-myelin staining to investigate the
      hypothalamus, amygdala and hippocampus in suicide victims with mood disorders (n
      = 11), non-suicidal mood disorder patients (n = 9) and control subjects (n = 23).
      Comparisons between the groups by using an ANCOVA showed a significant overall
      difference for the hypothalamus (p = 0.001) with reduced volumes in non-suicidal
      patients compared to suicide victims (p = 0.018) and controls (p = 0.006). To our
      surprise, the volumes between the suicide victims and controls did not differ
      significantly. For the amygdala and hippocampus no volume changes between the
      groups could be detected (all p values were n. s.). In conclusion our data
      suggest a structural hypothalamic pathology in non-suicidal mood disorder
      patients. The detected differences between suicidal and non-suicidal patients
      suggest that suicidal performances might be related to the degree of structural
      deficits. 

PMID- 24040807
TI  - Disruption of glutamate-glutamine-GABA cycle significantly impacts on suicidal
      behaviour: survey of the literature and own findings on glutamine synthetase.
AB  - The aetiology of suicide is complex and still not completely understood. The
      present communication, which consists of two parts, aims to shed some light on
      the role of amino acidergic neurotransmission in suicide. In the first part we
      provide an overview of the literature showing that with the exception of certain
      gamma-aminobutyric acid transporters, virtually all components of the glutamate
      glutamine- gamma-aminobutyric acid cycle are, in some way or other, abnormal in
      suicide victims, which indicates a prominent involvement of the glutamatergic and
      gammaaminobutyric acidergic neurotransmitter systems in suicidal behaviour. In
      the second part we present own immunohistochemical findings showing that
      densities of glutamine synthetase expressing glial cells in the mediodorsal
      thalamus as well as in the dorsolateral prefrontal and orbitofrontal cortex of
      schizophrenic suicide completers are significantly elevated compared with
      controls and non-suicide individuals with schizophrenia, thus calling into
      question the belief that cerebral glutamine synthetase deficit is indicative of
      suicidal behaviour. 

PMID- 24040808
TI  - Reconceptualizing adult neurogenesis: role for sphingosine-1-phosphate and
      fibroblast growth factor-1 in co-ordinating astrocyte-neuronal precursor
      interactions.
AB  - Despite the powerful induction of neurogenesis by sphingosine-1-phosphate (S1P),
      its study in the role of adult neurogenesis has been relatively neglected. S1P,
      via its differential effects at different S1P receptor subtypes, is a significant
      determinant of neuronal precursor/stem cell and astrocyte cellular organization.
      The variations in neurogenesis, classically modelled via the interactions of
      phosphatase and tensin homolog and Notch, are intimately associated with the co
      ordinated regulation of S1P and fibroblast growth factor-1. Incorporating S1P
      better explains the plasticity and cellular variations in astrocytes and
      progenitors as well as their interactions. This has treatment implications for
      both inducing and inhibiting neurogenesis, in conditions such as depression and
      macrocephaly associated autistic spectrum disorders respectively. Incorporating
      S1P and fibroblast growth factor-1 also provides a framework for conceptualizing
      the impact of peripheral inflammation, central inflammation, redox status and
      medication effects on neurogenesis, as well as future treatment targets. 

PMID- 24040809
TI  - Pharmacological prolyl hydroxylase domain inhibition as a therapeutic target for
      Parkinson's disease.
AB  - Previously published data from our laboratory demonstrated that pharmacological
      inhibition of a family of enzymes known as prolyl hydroxylase domain proteins
      prevents neurotoxicity associated with the acute 1-methyl-4- phenyl-1,2,3,6
      tetrahydropyridine intoxication model of Parkinson's disease in young animals. In
      this study, we assessed whether prolyl hydroxylase domain inhibition was
      neuroprotective in an inducible genetic dopaminergic glutathione depletion model
      previously characterized by our laboratory that more closely recapitulates the
      age-related and progressive nature of the human disease. Pharmacological prolyl
      hydroxylase domain inhibition via 3,4-dihydroxybenzoate was found to
      significantly attenuate hallmark mitochondrial dysfunction and loss of
      dopaminergic substantia nigral pars compacta neurons associated with this model.
      These studies further validate the possibility that prolyl hydroxylase domain
      inhibition may constitute a viable therapy for Parkinson's disease. 

PMID- 24040810
TI  - Pathogenesis of Alzheimer disease: role of oxidative stress, amyloid-beta
      peptides, systemic ammonia and erythrocyte energy metabolism.
AB  - Abeta exerts prooxidant or antioxidant effects based on the metal ion
      concentrations that it sequesters from the cytosol; at low metal ion
      concentrations, it is an antioxidant, whereas at relatively higher concentration
      it is a prooxidant. Thus Alzheimer disease (AD) treatment strategies based solely
      on the amyloid-beta clearance should be re-examined in light of the vast
      accumulating evidence that increased oxidative stress in the human brains is the
      key causative factor for AD. Accumulating evidence indicates that the reduced
      brain glucose availability and brain hypoxia, due to the relatively lower
      concentration of ATP and 2,3-diphosphoglycerate, may be associated with increased
      concentration of endogenous ammonia, a potential neurotoxin in the AD brains. In
      this review, we summarize the progress in this area, and present some of our
      ongoing research activities with regard to brain Amyloid-beta, systemic ammonia,
      erythrocyte energy metabolism and the role of 2,3-diphosphoglycerate in AD
      pathogenesis. 

PMID- 24040811
TI  - Targeting striatal metabotropic glutamate receptor type 5 in Parkinson's disease:
      bridging molecular studies and clinical trials.
AB  - Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed
      primarily on neurons and glial cells modulating the effects of glutamatergic
      neurotransmission. The pharmacological manipulation of these receptors has been
      postulated to be valuable in the management of some neurological disorders.
      Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for
      Parkinson's disease (PD) has been proposed, especially to manage the adverse
      symptoms associated to chronic treatment with classical PD drugs. Thus, the
      specific pharmacological blocking of mGlu5 receptors constitutes one of the most
      attractive non-dopaminergic-based strategies for PD management in general and for
      the L-DOPA-induced dyskinesia (LID) in particular. Overall, we provide here an
      update of the current state of the art of these mGlu5 receptor-based approaches
      that are under clinical study as agents devoted to alleviate PD symptoms.

PMID- 24040812
TI  - Novel perspectives for Parkinson's disease therapy: insights from the latest
      advances in disease pathophysiology, diagnostic and experimental tools and
      molecular targets.

PMID- 24040813
TI  - Induced pluripotent stem cell-based studies of Parkinson's disease: challenges
      and promises.
AB  - A critical step in the development of effective therapeutics to treat Parkinson's
      disease (PD) is the identification of molecular pathogenic mechanisms underlying
      this chronically progressive neurodegenerative disease. However, while animal
      models have provided valuable information about the molecular basis of PD, the
      lack of faithful cellular and animal models that recapitulate human
      pathophysiology is delaying the development of new therapeutics. The
      reprogramming of somatic cells to induced pluripotent stem cells (iPSC) using
      delivery of defined combinations of transcription factors is a groundbreaking
      discovery that opens great opportunities for modeling human diseases, including
      PD, since iPSC can be generated from patients and differentiated into disease
      relevant cell types, which would capture the patients' genetic complexity.
      Furthermore, human iPSC-derived neuronal models offer unprecedented access to
      early stages of the disease, allowing the investigation of the events that
      initiate the pathologic process in PD. Recently, human iPSC-derived neurons from
      patients with familial and sporadic PD have been generated and importantly they
      recapitulate some PD-related cell phenotypes, including abnormal alpha-synuclein
      accumulation in vitro, and alterations in the autophagy machinery. This review
      highlights the current PD iPSC-based models and discusses the potential future
      research directions of this field. 

PMID- 24040814
TI  - Steroid-dependent management of biological responses in the nervous system.

PMID- 24040815
TI  - Comparison of glucocorticoid receptor and epigenetically regulated genes in
      proliferating versus growth-arrested Neuro-2a cells.
AB  - In recent years, it has been established that environmental stress leaves
      enduring traces at distinct sites on the chromatin, accompanied by permanent
      alterations of gene transcription. This process depends on duration and extent of
      the discharge of stress hormones. Here, we aimed at identifying genes that are
      both regulated by the glucocorticoid receptor (GR) and display epigenetic
      features of transcriptional control. We used neuronal Neuro-2a cells as model
      system; cells were transiently transfected with GR and exposed to dexamethasone
      (Dex) for 2 days, either under conditions of cell proliferation or after serum
      deprivation-induced growth arrest. In parallel, Neuro-2a cells were treated with
      the histone deacetylase inhibitor trichostatin A. Comparison of gene expression
      profiles obtained from whole-genome microarray analyses revealed a network of
      genes that were GR-dependent and under control of epigenetic factors. Gene set
      enrichment analysis was performed in order to obtain insight into functional
      mechanisms implicated in stress hormone physiology. Dex response varied between
      proliferating and growth-arrested cells; enrichment was found for genes
      associated with metabolic pathways in proliferating cells, and for genes linked
      to inflammation in growth-arrested cells. The set of genes that were regulated by
      Dex under both growth conditions (proliferation and arrest) as well as by
      trichostatin A - (under cell proliferation) was enriched in mRNA transcripts
      encoding proteins which play a role in development and homeostasis. In summary,
      this study introduces a conceptual approach and incipient proof-of-concept for
      the identification of candidate genes that might be epigenetically programmed by
      activated GR.

PMID- 24040816
TI  - Contribution of glucocorticoids and glucocorticoid receptors to the regulation of
      neurodegenerative processes.
AB  - Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led
      rapidly to their first clinical application, about 70 years ago, for treatment of
      rheumatoid arthritis. To this day GCs are used in diseases that have an
      inflammatory component. However, their use is carefully monitored because of
      harmful side effects. GCs are also synonymous with stress and adaptation. In CNS,
      GC binds and activates high affinity mineralocorticoid receptor (MR) and low
      affinity glucocorticoid receptor (GR). GR, whose expression is ubiquitous, is
      only activated when GC levels rise as during circadian peak and in response to
      stress. Numerous recent studies have yielded important and new insights on the
      mechanisms concerning pulsatile secretory pattern of GCs as well as various
      processes that tightly control their synthesis via hypothalamic-pituitary-adrenal
      (HPA) axis involving regulated release of corticotropin-releasing hormone (CRH)
      and adrenocorticotropic hormone (ACTH) from hypothalamus and pituitary,
      respectively. GR modulates neuronal functions and viability through both genomic
      and non-genomic actions, and importantly its transcriptional regulatory activity
      is tightly locked with GC secretory pattern. There is increasing evidence
      pointing to involvement of GC-GR in neurodegenerative disorders. Patients with
      Alzheimer's or Parkinson's or Huntington's disease show chronically high cortisol
      levels suggesting changes occurring in controls of HPA axis. In experimental
      models of these diseases, chronic stress or GC treatment was found to exacerbate
      both the clinical symptoms and neurodegenerative processes. However, recent
      evidence also shows that GC-GR can exert neuroprotective effects. Thus, for any
      potential therapeutic strategies in these neurodegenerative diseases we need to
      understand the precise modifications both in HPA axis and in GR activity and find
      ways to harness their protective actions. 

PMID- 24040818
TI  - Neuroprotective effects of non-classical estrogen-like signaling activators: from
      mechanism to potential implications.
AB  - The gonadal steroid 17beta-estradiol (E2) has shown powerful cytoprotective
      effect on cells. In addition to classical genomic mechanisms of action, E2 also
      exerts non-classical effects on intracellular signal transduction. Extensive
      studies during the past two decades have provided evidence that the E2-induced
      non-classical signaling on second messenger molecules plays a critical role in
      the neuroprotective effect of E2. These observations provide a unique basis for
      developing non-classical estrogen-like signaling activators that may have
      potential for clinical use in neuroprotection. In spite of the extensive research
      over the past decade reviewed here, we are just starting to appreciate the
      importance and potential of these compounds. Hence, we first describe the
      molecular characteristics and effects of these activators. Second, we survey
      recent data as to possible mechanisms underlying the ameliorative actions of
      selective non-classical estrogen-like signaling activation. In addition, the
      pitfalls and future aspects of "non-classical"-line activators and its clinical
      relevance will also be discussed. 

PMID- 24040819
TI  - Molecular basis of mineralocorticoid receptor action in the nervous system.
AB  - The most relevant biological action of aldosterone in epithelial tissues is the
      regulation of sodium reabsorption through binding to the mineralocorticoid
      receptor (MR). Glucocorticoids also bind with high affinity to MR, which is
      usually protected by the enzyme 11beta-hydroxysteroid dehydrogenase. This
      activity prevents MR activation by cortisol despite the large prevalence of this
      steroid in plasma. Nonetheless, there are some aspects of the mechanism of action
      of MR that are not entirely explained by this competitive metabolic mechanism of
      protection. The picture is even more complicated in those tissues such as the
      nervous system where the enzyme is expressed at very low levels or is directly
      absent in various areas of the brain. Therefore, other cellular and molecular
      mechanisms must also intervene to allow specific aldosterone biological effects
      in the presence of overwhelming concentrations of glucocorticoids. In this
      article, we discuss some possible mechanisms that permit the specificity of
      action for each type of steroid, including those related to the recently
      discovered novel molecular mechanism of activation of corticosteroid receptors
      and the structural requirements of a given ligand to favor the mineralocorticoid
      action via MR. The relative contribution of these mechanisms may vary in
      different target cells allowing the fine tuning of cellular functions depending
      on the degree of cooperation between steroids, receptors, chaperones associated
      to receptors, and other factors. All these regulatory interactions can be altered
      in some pathophysiological situations, most of them related to stressing
      situations. 

PMID- 24040821
TI  - Therapeutic effects of progesterone in animal models of neurological disorders.
AB  - Substantial evidence supports that progesterone exerts many functions in the
      central and peripheral nervous system unrelated to its classical role in
      reproduction. In this review we first discussed progesterone effects following
      binding to the classical intracellular progesterone receptors A and B and several
      forms of membrane progesterone receptors, the modulation of intracellular
      signalling cascades and the interaction of progesterone reduced metabolites with
      neurotransmitter receptors. We next described our results involving animal models
      of human neuropathologies to elucidate the protective roles of progesterone. We
      described: (a) the protective and promyelinating effects of progesterone in
      experimental spinal cord injury; (b) the progesterone protective effects exerted
      upon motoneurons in the degenerating spinal cord of Wobbler mouse model of
      amyotropic lateral sclerosis; (c) the protective and anti-inflammatory effects of
      progesterone in the murine experimental autoimmune encephalomyelitis model of
      multiple sclerosis and after lysolecithin demyelination; (d) the progesterone
      prevention of nociception and neuropathic pain which follow spinal cord injury;
      and (e) the protective effect of progesterone in experimental ischemic stroke.
      Whenever available, the molecular mechanisms involved in these progesterone
      effects were examined. The multiplicity of progesterone beneficial effects has
      opened new venues of research for neurological disorders. In this way, results
      obtained in animal models could provide the basis for novel therapeutic
      strategies and pre-clinical studies. 

PMID- 24040817
TI  - Pathogenic mechanisms and therapeutic strategies in spinobulbar muscular atrophy.
AB  - We review the genetic and clinical features of spinobulbar muscular atrophy
      (SBMA), a progressive neuromuscular disorder caused by a CAG/glutamine tract
      expansion in the androgen receptor. SBMA was the first polyglutamine disease to
      be discovered, and we compare and contrast it with related degenerative disorders
      of the nervous system caused by expanded glutamine tracts. We review the cellular
      and animals models that have been most widely used to study this disorder, and
      highlight insights into disease pathogenesis derived from this work. These model
      systems have revealed critical aspects of the disease, including its hormone
      dependence, a feature that underlies disease occurrence only in men with the
      mutant allele. We discuss how this and other findings have been translated to
      clinical trials for SBMA patients, and examine emerging therapeutic targets that
      have been identified by recent work. 

PMID- 24040822
TI  - Overlapping molecular signatures in Parkinson's patients' leukocytes before and
      after treatment and in mouse model brain regions.
AB  - Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease
      with worldwide increasing incidence. PD is the second most prevalent
      neurodegenerative disease and the first that involves motor symptoms. The great
      majority of cases, defined as sporadic with non-familial disease, show a highly
      variable risk of disease due to environmental and genetic factors that remain
      largely unknown. Furthermore, the neurodegenerative process typically initiates
      decades prior to the appearance of hallmark motor symptoms; therefore, clinical
      diagnosis is enabled only when most of the relevant neurons have died and current
      treatment is palliative at best. Here, we review the application of genomic scale
      microarray based research aimed to enable early diagnosis and identify novel
      targets for therapeutic intervention. We demonstrate that blood leukocytes can
      serve as a feasible and reliable tissue source to test for disease-induced and
      treatment-related transcript changes. We cover our reports of transcription and
      alternative splicing modifications in PD patient's leukocytes based on 3' and
      exon microarray analyses and the identified inflammatory modulations. We further
      describe the effects of deep brain stimulation (DBS) neurosurgery on the
      leukocyte transcripts as reflecting the patient's neurological status. A focus is
      gained on common genes identified both in the molecular signature of human PD
      leukocytes and in brain RNA from engineered PD mouse models subjected to risk and
      protection manipulations. Finally, we discuss potential future directions of high
      throughput RNA research as facilitators of the PD knowledge base through next
      generation sequencing technologies of both long and short RNA transcripts
      including microRNAs.

PMID- 24040820
TI  - The role of FKBP5 in mood disorders: action of FKBP5 on steroid hormone receptors
      leads to questions about its evolutionary importance.
AB  - Research on the FKBP5 gene and FKBP51 protein has more than doubled since the
      discovery that polymorphisms in this gene could alter treatment outcomes and
      depressive behavior in humans. This coincided with other data suggesting that the
      stress hormone axis contributes to the development of numerous mental illnesses.
      As a result, FKBP51 now lies at the heart of the research of many stress related
      psychiatric disorders, which has led to advances in the understanding of this
      protein and its role in humans and in animal models. Specifically, FKBP5-/- mice
      and a naturally existing overexpression of FKBP5 in 3 genera of new world monkeys
      have helped understand the effects of FKBP5 in vivo. This review will highlight
      these finding as well as discuss the current evolutionary need for the FKBP5
      gene. 

PMID- 24040823
TI  - Receptor heteromers in Parkinson's disease and L-DOPA-induced dyskinesia.
AB  - Parkinson's disease (PD) and L-DOPA-induced dyskinesia, a major complication of
      treatment of PD, are associated with molecular and functional alterations
      occurring into the medium spiny neurons (MSNs) of the dorsal striatum, a key
      areas involved in the control of motor activity. MSNs are regulated by several
      neurotransmitter systems including dopamine, glutamate and adenosine via
      activation of distinct receptors. Increasing evidence suggest that interactions
      among systems are mediated by different mechanisms including the formation of
      receptor heterodimers. The current view of G protein-coupled receptors
      organization, in fact, assumes that they do not work as monomeric units, but are
      part of heterodimeric complexes or of high order heteromers, where other
      receptors and ancillary proteins are coclustered. This organization implies that
      the pharmacological and signalling properties of these receptors may depend on
      the molecular composition of the receptor heteromers where they are clustered and
      may be differentially modulated in physiological or pathological conditions.
      Here, we provide an overview of the functional implications of physical
      interactions among dopamine, glutamate and adenosine receptors, their relevance
      for striatal MSNs activity and their involvement in the physiopathology of PD and
      dyskinesia. 

PMID- 24040824
TI  - Synaptic dysfunction in synucleinopathies.
AB  - Pathological aggregation of alpha-synuclein as Lewy-bodies and neurites is a
      hallmark of a group of neurodegenerative disorders named alpha-synucleinopathies.
      It is becoming apparent that alpha-synuclein facilitates presynaptic neuronal
      function in the brain, and events leading to its aggregation produce marked
      disruption of neurotransmitter release mechanism. We discuss here the literature
      related to the function of alpha-synuclein at the neuronal synapse in
      synucleinopathies brains and corresponding animal models. 

PMID- 24040825
TI  - Commentary: multifactoriality of amytrophic lateral sclerosis: linking unfolded
      proteins to oxidative stress in microglia.

PMID- 24040826
TI  - The effect of translationally controlled tumour protein (TCTP) on programmed cell
      death in plants.
AB  - BACKGROUND: Translationally controlled tumour protein (TCTP), a well known
      protein of the animal kingdom, was shown to be a Ca(2+)-binding protein with
      important functions in many different cellular processes (e.g. protection against
      stress and apoptosis, cell growth, cell cycle progression, and microtubule
      organization). However, only little is known about TCTP in plants. Transcript and
      protein levels of plant TCTPs were shown to be altered by various stress
      conditions (e.g. cold, salt, draught, aluminium, and pathogen infection), and
      Arabidopsis thaliana TCTP (AtTCTP) was described as an important regulator of
      growth. The aim of this study was to further characterize plant TCTP relating to
      one of its major functions in animals: the protection against cell death.
      RESULTS: We used two different activators of programmed cell death (PCD) in
      plants: the mammalian pro-apoptotic protein BAX and tunicamycin, an inhibitor of
      glycosylation and trigger of unfolded protein response (UPR). Over-expression of
      AtTCTP significantly decreased cell death in tobacco leaf discs in both studies.
      A (45)Ca overlay assay showed AtTCTP to be a Ca(2+)-binding protein and
      localization experiments revealed cytosolic distribution of AtTCTP-GFP in
      Arabidopsis seedlings. CONCLUSIONS: Our study showed cytoprotective effects of
      plant TCTP for the first time. Furthermore, we showed the ability of AtTCTP to
      bind to Ca(2+) and its cytosolic distribution within the cell. If these results
      are combined, two putative modes of action can be assumed: 1) AtTCTP acts as
      Ca(2+) sequester, preventing PCD by reducing cytosolic Ca(2+) levels as described
      for animals. 2) AtTCTP could directly or indirectly interact with other cytosolic
      or membrane-bound proteins of the cell death machinery, thereby inhibiting cell
      death progression. As no homologous proteins of the anti-apoptotic machinery of
      animals were found in plants, and functional homologues still remain to be
      elucidated, future work will provide more insight.

PMID- 24040827
TI  - Exploring authentic skim and nonfat dry milk powder variance for the development
      of nontargeted adulterant detection methods using near-infrared spectroscopy and
      chemometrics.
AB  - A multinational collaborative team led by the U.S. Pharmacopeial Convention is
      currently investigating the potential of near-infrared (NIR) spectroscopy for
      nontargeted detection of adulterants in skim and nonfat dry milk powder. The
      development of a compendial method is challenged by the range of authentic or
      nonadulterated milk powders available worldwide. This paper investigates the
      sources of variance in 41 authentic bovine skim and nonfat milk powders as
      detected by NIR diffuse reflectance spectroscopy and chemometrics. Exploratory
      analysis by principal component analysis and varimax factor rotation revealed
      significant variance in authentic samples and highlighted outliers from a single
      manufacturer. Spectral preprocessing and outlier removal methods reduced ambient
      and measurement sources of variance, most likely linked to changes in moisture
      together with sampling, preparation, and presentation factors. Results indicate
      that significant chemical variance exists in different skim and nonfat milk
      powders that will likely affect the performance of adulterant detection methods
      by NIR spectroscopy. 

PMID- 24040828
TI  - Pd-catalyzed alkynylation of 2-chloroacetates and 2-chloroacetamides with
      potassium alkynyltrifluoroborates.
AB  - The synthesis of beta,gamma-alkynyl esters and amides using air-stable potassium
      alkynyltrifluoroborates as nucleophilic partners in a mild Suzuki-Miyaura cross
      coupling reaction has been achieved. Propargyl esters and amides were obtained in
      high yields using a low catalyst loading, and the substrate scope of the reaction
      has been significantly improved over previous methods. 

PMID- 24040829
TI  - Lingual leiomyomatous hamartoma with bifid tip and ankyloglossia in a patient
      without oral-facial-digital syndrome: a case report and literature review.
AB  - Here is a rare case of lingual leiomyomatous hamartoma (LLH) with bifid tongue
      tip and tongue-tie in a patient with non-oral-facial-digital syndrome (OFDS). A
      29-year-old male consulted for a painless tumor over the midline of the tongue
      dorsum measuring 2 * 1.5 cm. The tumor was excised and the tongue-tie was
      corrected. Diagnosis of LLH was based on histo-pathologic and immuno
      histochemical studies. The epidemiologic data and differential diagnosis of LLH,
      as well as related literature, are discussed. To date, only 14 cases of LLH have
      been reported in English literature. This may be the first reported case of LLH
      with bifid tip and ankyloglossia in a non-OFDS patient. 

PMID- 24040830
TI  - A survey of visitors on Swedish livestock farms with reference to the spread of
      animal diseases.
AB  - BACKGROUND: In addition to livestock movements, other between-farm contacts such
      as visitors may contribute to the spread of contagious animal diseases. Knowledge
      about such contacts is essential for contingency planning. Preventive measures,
      risk-based surveillance and contact tracing may be facilitated if the frequency
      and type of between-farm contacts can be assessed for different types of farms.
      The aim of this study was to investigate the frequency and types of visitors on
      farms with cloven-hoofed animals in Sweden and to analyse whether there were
      differences in the number of visitors attributable to region, season, and type of
      herd. Data were collected from Swedish farmers through contact-logs covering two
      week periods during four different seasons. RESULTS: In total, 482 (32%) farmers
      filled in the contact log for at least one period and the data represent 18,416
      days. The average number of professional and non-professional visitors per day
      was 0.3 and 0.8, respectively. Whereas the number of professional visitors seemed
      to increase with increasing herd size, this relation was not seen for non
      professional visits. The mean numbers of visitors per day were highest in the
      summer and in the farm category 'small mixed farm'. Reports of the visitors'
      degree of contact with the animals showed that veterinarians, AI-technicians,
      animal transporters and neighbours were often in direct contact with the animals
      or entered the stables and 8.8% of the repairmen were also in direct contact with
      animals, which was unexpected. In a multivariable analysis, species, herd size
      and season were significantly associated with the number of professional visitors
      as well as the number of visitors in direct contact with the animals. CONCLUSION:
      In conclusion there was a large variation between farms in the number and type of
      contacts. The number of visitors that may be more likely to spread diseases
      between farms was associated with animal species and herd size.

PMID- 24040832
TI  - 3D Branched nanowire photoelectrochemical electrodes for efficient solar water
      splitting.
AB  - We report the systematic study of 3D ZnO/Si branched nanowire (b-NW)
      photoelectrodes and their application in solar water splitting. We focus our
      study on the correlation between the electrode design and structures (including
      Si NW doping, dimension of the trunk Si and branch ZnO NWs, and b-NW pitch size)
      and their photoelectrochemical (PEC) performances (efficiency and stability)
      under neutral conditions. Specifically, we show that for b-NW electrodes with
      lightly doped p-Si NW core, larger ZnO NW branches and longer Si NW cores give a
      higher photocathodic current, while for b-NWs with heavily doped p-Si NW trunks
      smaller ZnO NWs and shorter Si NWs provide a higher photoanodic current.
      Interestingly, the photocurrent turn-on potential decreases with longer p-Si NW
      trunks and larger ZnO NW branches resulting in a significant photocathodic turn
      on potential shift of ~600 mV for the optimized ZnO/p-Si b-NWs compared to that
      of the bare p-Si NWs. A photocathode energy conversion efficiency of greater than
      2% at -1 V versus Pt counter electrode and in neutral solution is achieved for
      the optimized ZnO/p-Si b-NW electrodes. The PEC performances or incident photon
      to-current efficiency are further improved using Si NW cores with smaller pitch
      size. The photoelectrode stability is dramatically improved by coating a thin
      TiO2 protection layer using atomic-layer deposition method. These results provide
      very useful guidelines in designing photoelectrodes for selective solar water
      oxidation/reduction and overall spontaneous solar fuel generation using low cost
      earth-abundant materials for practical clean solar fuel production.

PMID- 24040831
TI  - More mental health problems after divorce in couples with high pre-divorce
      alcohol consumption than in other divorced couples: results from the HUNT-study.
AB  - BACKGROUND: Divorce is associated with mental health problems, and heavy drinking
      is related to higher risk of divorce. Less is known about the effects of divorce
      in couples where one or both drinks heavily. There are, however, reasons to
      expect different consequences of divorce in heavy risk using couples compared to
      other couples. Spouses of abusers may experience the divorce as a relief, whereas
      abusers may find it extra difficult to be left single. The aim of the study is to
      compare the effect of divorce on mental health in heavy drinking couples to the
      effect in couples who drink less. METHODS: Registry data were matched with data
      from the Nord-Trondelag Health Study (HUNT 1 (T1) and 2 (T2)), enabling
      longitudinal analyses of approximately 11,000 couples. Interaction terms between
      1) alcohol use on T1 and divorce between T1 and T2 (11 year time lag), and 2)
      alcohol use on T1 and time since divorce at T2 for all divorced couples were
      tested to examine changes in mental health between T1 and T2 for a) spouses of
      high-risk compared to low-risk users, and b) high-risk compared to low-risk users
      themselves. Data were analyzed using multivariate analysis of variance. RESULTS:
      There was a general effect of divorce on change in mental health between T1 and
      T2. We observed a significantly stronger worsening in mental health in female
      high-risk users and their spouses than in divorced low-risk users and their
      spouses. The results also suggest that the strain after divorce lasts longer in
      women with a high alcohol consumption and their spouses. CONCLUSIONS: Divorce
      seems to affect couples where one or both drink heavily more than couples with a
      low consumption. Also there was some evidence of a slower healing of mental
      health problems after divorce in alcohol exposed couples than in other couples.
      The results only reached significance for female high consumers and their
      spouses, but due to limited statistical power, safe conclusions about gender
      specific effects cannot be drawn.

PMID- 24040833
TI  - Self-assembly of gold nanoparticles on poly(allylamine hydrochloride) nanofiber:
      a new route to fabricate "necklace" as single electron devices.
AB  - Fabrication of a percolating conductive device exhibiting "necklace-like
      morphology" is being reported utilizing a new route. This device was fabricated
      by exploiting the electrostatic self-assembly of citrate capped negatively
      charged Au nanoparticles (NPs) (60 nm diameter) over positively charged
      poly(allylamine hydrochloride) (PAH) fibrous scaffold and followed by synthesis
      of small Au NPs (~10 nm) on the PAH surface. These 10 nm Au NPs were selectively
      synthesized over the PAH fiber surface using the surface catalyzed reduction of
      Au precursor (HAuCl4), leading to a continuous conducting network. This
      conducting device demonstrated a room temperature (RT) Coulomb-blockade
      characteristic, which is indicative of "single electron device". The deposition
      of Au NPs was directed by the diameter of PAH fibers and UV-irradiation exposure
      time used during the synthesis process. The average diameter of the fibers was in
      the ~100-150 nm range, and the polyelectrolyte (PAH) was fabricated using the
      electrospinning technique. The size of these fibers was controlled by tuning the
      physical properties of PAH solution. Exposure of UV-irradiation for 25 min was
      sufficiently enough to deposit Au NPs in close proximity to each other. Longer
      exposure time (~60 min) resulted in a device which showed linear Ohmic current
      voltage (I-V) behavior. The present process is reproducible, efficient, and
      resulted in a structurally stable and robust device. 

PMID- 24040835
TI  - The natural product dihydrotanshinone I provides a prototype for uncharged
      inhibitors that bind specifically to the acetylcholinesterase peripheral site
      with nanomolar affinity.
AB  - Cholinergic synaptic transmission often requires extremely rapid hydrolysis of
      acetylcholine by acetylcholinesterase (AChE). AChE is inactivated by
      organophosphates (OPs) in chemical warfare nerve agents. The resulting
      accumulation of acetylcholine disrupts cholinergic synaptic transmission and can
      lead to death. A potential long-term strategy for preventing AChE inactivation by
      OPs is based on evidence that OPs must pass through a peripheral site or P-site
      near the mouth of the AChE active site gorge before reacting with a catalytic
      serine in an acylation site or A-site at the base of the gorge. An ultimate goal
      of this strategy is to design compounds that bind tightly at or near the P-site
      and exclude OPs from the active site while interfering minimally with the passage
      of acetylcholine. However, to target the AChE P-site with ligands and potential
      drugs that selectively restrict access, much more information must be gathered
      about the structure-activity relationships of ligands that bind specifically to
      the P-site. We apply here an inhibitor competition assay that can correctly
      determine whether an AChE inhibitor binds to the P-site, the A-site, or both
      sites. We have used this assay to examine three uncharged, natural product
      inhibitors of AChE, including aflatoxin B1, dihydrotanshinone I, and territrem B.
      The first two of these inhibitors are predicted by the competition assay to bind
      selectively to the P-site, while territrem B is predicted to span both the P- and
      A-sites. These predictions have recently been confirmed by X-ray crystallography.
      Dihydrotanshinone I, with an observed binding constant (KI) of 750 nM, provides a
      good lead compound for the development of high-affinity, uncharged inhibitors
      with specificity for the P-site. 

PMID- 24040834
TI  - The Human Genome Project: big science transforms biology and medicine.
AB  - The Human Genome Project has transformed biology through its integrated big
      science approach to deciphering a reference human genome sequence along with the
      complete sequences of key model organisms. The project exemplifies the power,
      necessity and success of large, integrated, cross-disciplinary efforts - so
      called 'big science' - directed towards complex major objectives. In this
      article, we discuss the ways in which this ambitious endeavor led to the
      development of novel technologies and analytical tools, and how it brought the
      expertise of engineers, computer scientists and mathematicians together with
      biologists. It established an open approach to data sharing and open-source
      software, thereby making the data resulting from the project accessible to all.
      The genome sequences of microbes, plants and animals have revolutionized many
      fields of science, including microbiology, virology, infectious disease and plant
      biology. Moreover, deeper knowledge of human sequence variation has begun to
      alter the practice of medicine. The Human Genome Project has inspired subsequent
      large-scale data acquisition initiatives such as the International HapMap
      Project, 1000 Genomes, and The Cancer Genome Atlas, as well as the recently
      announced Human Brain Project and the emerging Human Proteome Project. 

PMID- 24040836
TI  - Capsaicin delivery into the skin with lipidic nanoparticles for the treatment of
      psoriasis.
AB  - The study aims to explore the potential of solid lipid nanoparticles (SLNs) and
      nanostructured lipid carriers (NLCs) in improving the topical delivery of
      capsaicin (CAP) by in vitro and in vivo studies. The lipidic nanoparticles were
      prepared by solvent diffusion method and were characterized for average particle
      size, zeta potential and entrapment efficiency. TEM photomicrographs revealed
      that the particles were nanometric in size. Higher amount of CAP can be
      encapsulated in the NLCs (87.4 +/- 3.28) as compared with SLNs (79.7 +/- 2.93%).
      The cumulative amounts of CAP permeated through the skin and retained in the SC
      were higher in the case of NLCs as compared with plain drug solution and SLNs.
      SLNs and NLCs exhibited minimum to no irritation. All the results concluded that
      NLCs and SLNs have shown a good ability to increase drug accumulation in the
      various skin layers but NLCs may be a more potential carrier for topical delivery
      of CAP for an effective therapy of psoriasis.

PMID- 24040837
TI  - A synthesis of all stereoisomers of tenuecyclamide A employing a fluorous-Fmoc
      strategy.
AB  - A concise liquid-phase combinatorial synthesis of all stereoisomers of
      Tenuecyclamide A was achieved using a mixture of D-/L-alanine with each
      stereoisomer encoded by a different f-Fmoc tag. The synthetic strategy using f
      Fmoc reagents as the protecting group for amino acids has been demonstrated to be
      a useful method for diverse polypeptide analogue synthesis.

PMID- 24040838
TI  - Preparation of non-heme {FeNO}7 models of cysteine dioxygenase: sulfur versus
      nitrogen ligation and photorelease of nitric oxide.
AB  - We present the synthesis and spectroscopic characterization of [Fe(NO)(N3PyS)]BF4
      (3), the first structural and electronic model of NO-bound cysteine dioxygenase.
      The nearly isostructural all-N-donor analogue [Fe(NO)(N4Py)](BF4)2 (4) was also
      prepared, and comparisons of 3 and 4 provide insight regarding the influence of S
      vs N ligation in {FeNO}(7) species. One key difference occurs upon
      photoirradiation, which causes the fully reversible release of NO from 3, but not
      from 4. 

PMID- 24040839
TI  - Occurrence of brominated flame retardants in black thermo cups and selected
      kitchen utensils purchased on the European market.
AB  - In order to screen for the presence of a recycled polymer waste stream from waste
      electric and electronic equipment (WEEE), a market survey was conducted on black
      plastic food-contact articles (FCA). An analytical method was applied combining X
      ray fluorescence spectrometry (XRF) with thermal desorption gas chromatography
      coupled with mass spectrometry (thermal desorption GC-MS). Firstly, XRF
      spectrometry was applied to distinguish bromine-positive samples. Secondly,
      bromine-positive samples were submitted for identification by thermal desorption
      GC-MS. Generally, the bromine-positive samples contained mainly technical
      decabromodiphenyl ether (decaBDE). Newer types of BFRs such as
      tetrabromobisphenol A (TBBPA), tetrabromobisphenol A bis(2,3-dibromopropyl),
      ether (TBBPA-BDBPE) and decabromodiphenylethane (DBDPE), replacing the
      polybrominated diphenyleters (PBDEs) and polybrominated diphenyls (PBBs), were
      also identified. In none of the tested samples were PBBs or
      hexabromocyclododecane (HBCD) found. Polymer identification was carried out using
      Fourier-transformed infrared spectroscopy measurement (FTIR) on all samples. The
      results indicate that polypropylene-polyethylene copolymers (PP-PE) and mainly
      styrene-based food-contact materials, such as acrylonitrile-butadiene-styrene
      (ABS) have the highest risk of containing BFRs. 

PMID- 24040840
TI  - Terahertz vibrations of crystalline acyclic and cyclic diglycine: benchmarks for
      London force correction models.
AB  - Terahertz spectroscopy provides direct information concerning weak intermolecular
      forces in crystalline molecular solids and therefore acts as an excellent method
      for calibrating and evaluating computational models for noncovalent interactions.
      In this study, the low-frequency vibrations of two dipeptides were compared,
      acyclic diglycine and cyclic diglycine, as benchmark systems for gauging the
      performance of semiempirical London force correction approaches. The diglycine
      samples were investigated using pulsed terahertz spectroscopy from 10 to 100 cm(
      1) and then analyzed using solid-state density functional theory (DFT) augmented
      with existing London force corrections, as well as a new parametrization (DFT-DX)
      based on known experimental values. The two diglycine molecules provide a useful
      test for the applied models given their similarities, but more importantly the
      differences in the intermolecular forces displayed by each. It was found that all
      of the considered London force correction models were able to generate diglycine
      crystal structures of similar accuracy, but considerable variation occurred in
      their abilities to predict terahertz frequency vibrations. The DFT-DX
      parametrization was particularly successful in this investigation and shows
      promise for the improved analysis of low-frequency spectra. 

PMID- 24040841
TI  - Co-assessment of cell cycle and micronucleus frequencies demonstrates the
      influence of serum on the in vitro genotoxic response to amorphous monodisperse
      silica nanoparticles of varying sizes.
AB  - Serum proteins have been shown to modulate the cytotoxic and genotoxic responses
      to nanomaterials. The aim was to investigate the influence of serum on the
      induction of micronuclei (MN) by nanoparticles (NPs) of different sizes.
      Therefore, A549 human lung carcinoma cells and amorphous monodisperse silica
      nanoparticles (SNPs) were used as models. Assessment of the cell viability, cell
      cycle changes and induction of MN by SNPs ranging from 12 to 174 nm was performed
      in presence or absence of serum, applying the in vitro flow cytometry-based MN
      assay. Here, it has been demonstrated that serum has an influence on these end
      points, with a lower cell viability in absence of serum compared with the
      presence of serum. Further, cell cycle changes, specifically, G1 and S-phase
      arrest, were observed in absence of serum for four out of six SNPs tested. A size
      dependent MN induction was observed: larger SNPs being more active in absence of
      serum. In addition, the serum influence was characterised by a size-dependency
      for cytotoxic and genotoxic effects, with a higher influence of serum for smaller
      particles. The data indicate that the in vitro micronucleus assay in presence and
      absence of serum could be advised for hazard assessment because it demonstrates a
      higher sensitivity in serum-free conditions than in conditions with serum.
      However, this recommendation applies only if the cell line used is able to
      proliferate under serum-free conditions because cell division is a prerequisite
      for MN expression.

PMID- 24040843
TI  - Corneal topography and corneal thickness in children.
AB  - PURPOSE: To evaluate the corneal topography, thickness, and elevation (anterior
      and posterior corneal surface) in children. METHODS: One hundred eyes of 100
      patients with a mean +/- standard deviation age of 10.6 +/- 2.7 years (range: 5
      to 15 years) were imaged. The corneal elevation maps were classified into regular
      ridge, irregular ridge, incomplete ridge, island, and unclassified patterns.
      RESULTS: Mean simulated keratometry (Sim K) astigmatism was -0.69 +/- 0.35
      diopters (D) with mean maximum and minimum keratometry (K) of 44.26 +/- 1.55 and
      43.56 +/- 1.57 D, respectively. Mean astigmatism and refractive power in the 3-
      and 5-mm zones was 0.64 +/- 0.36, 43.85 +/- 1.53 and 0.78 +/- 0.5, 43.41 +/-
      1.48, respectively. The thinnest site on the cornea had an average thickness of
      540 +/- 34.03 MUm. This site was most commonly located in the inferotemporal
      quadrant in 61% of eyes, followed by the superotemporal quadrant in 31%. Among
      the nine regions of the cornea evaluated, the central cornea had the lowest
      average thickness of 540 +/- 34.03 MUm and the superonasal cornea had the
      greatest average thickness of 628 +/- 38.94 MUm. The most common anterior corneal
      elevation pattern was the incomplete ridge (52%), followed by the island pattern.
      The incomplete ridge was most commonly observed on the posterior corneal
      elevation map (35%). CONCLUSIONS: These results provide normal standards for
      elevation and curvature topography and corneal thickness in children. These data
      may prove useful as a reference for future comparative studies of different
      corneal diseases in children.

PMID- 24040844
TI  - Effect of carbon nanotubes on the transport and retention of bacteria in
      saturated porous media.
AB  - This study investigated the influence of carbon nanotubes (CNTs) on the transport
      and retention behaviors of bacteria (E. coli) in packed porous media at both low
      and high ionic strength in NaCl and CaCl2 solutions. At low ionic strengths (5 mM
      NaCl and 0.3 mM CaCl2), both breakthrough curves and retained profiles of
      bacteria with CNTs (both 5 and 10 mg L(-1)) were equivalent to those without
      CNTs, indicating the presence of CNTs did not affect the transport and retention
      of E. coli at low ionic strengths. The results were supported by those from cell
      characterization tests (i.e., viability, surface properties, sizes), which showed
      no significant difference between with and without CNTs. In contrast,
      breakthrough curves of bacteria with CNTs were lower than those without CNTs at
      high ionic strengths (25 mM NaCl and 1.2 mM CaCl2), suggesting that the presence
      of CNTs decreased cell transport at high ionic strengths. The enhanced bacterial
      deposition in the presence of CNTs was mainly observed at segments near the
      column inlet, leading to much steeper retained profiles relative to those without
      CNTs. Additional transport experiments conducted with sand columns predeposited
      with CNTs revealed that the codeposition of bacteria with CNTs, as well as the
      deposition of the cell-CNTs cluster formed in cell suspension due to cell
      bridging effect, largely contributed to the increased deposition of bacteria at
      high ionic strengths in porous media. 

PMID- 24040845
TI  - Gene-environment interplay in the link of friends' and nonfriends' behaviors with
      children's social reticence in a competitive situation.
AB  - This study used a genetically informed design to assess the effects of friends'
      and nonfriends' reticent and dominant behaviors on children's observed social
      reticence in a competitive situation. Potential gene-environment correlations
      (rGE) and gene-environment interactions (GxE) in the link between (a) friends'
      and nonfriends' behaviors and (b) children's social reticence were examined. The
      sample comprised 466 twin children (i.e., the target children), each of whom was
      assessed in kindergarten together with a same-sex friend and two nonfriend
      classmates of either sex. Multilevel regression analyses revealed that children
      with a genetic disposition for social reticence showed more reticent behavior in
      the competitive situation and were more likely to affiliate with reticent friends
      (i.e., rGE). Moreover, a higher level of children's reticent behavior was
      predicted by their friends' higher social reticence (particularly for girls) and
      their friends' higher social dominance, independently of children's genetic
      disposition. Children's social reticence was also predicted by their nonfriends'
      behaviors. Specifically, children were less reticent when male nonfriends showed
      high levels of social reticence in the competitive situation, and this was
      particularly true for children with a genetic disposition for social reticence
      (i.e., GxE). Moreover, children genetically vulnerable for social reticence
      seemed to foster dominant behavior in their female nonfriend peers (i.e., rGE).
      In turn, male nonfriends seemed to be more dominant as soon as the target
      children were reticent, even if the target children did not have a stable genetic
      disposition for this behavior.

PMID- 24040846
TI  - Perspective taking and empathic concern in adolescence: gender differences in
      developmental changes.
AB  - Empathy is an important social skill and is believed to play an essential role in
      moral development (Hoffman, 2000). In the present longitudinal study, the authors
      investigated adolescents' development of perspective taking and empathic concern
      from age 13 to 18 years (mean age at Wave 1 = 13 years, SD = 0.46) and examined
      its association with pubertal status. Adolescents (283 boys, 214 girls) reported
      for 6 consecutive years on their dispositional perspective taking and empathic
      concern and for 4 consecutive years on pubertal status. Latent growth curve
      modeling revealed gender differences in levels and developmental trends. Gender
      differences in perspective taking emerged during adolescence, with girls'
      increases being steeper than those of the boys. Girls also showed higher levels
      of empathic concern than did boys. Whereas girls' empathic concern remained
      stable across adolescence, boys showed a decrease from early to middle
      adolescence with a rebound to the initial level thereafter. Boys who were
      physically more mature also reported lower empathic concern than did their less
      physically developed peers. The current study supports theoretical notions that
      perspective taking develops during adolescence as a result of cognitive
      development. Moreover, the results suggest that pubertal maturation plays a role
      in boys' development of empathic concern.

PMID- 24040847
TI  - Effect of cimetidine, a model drug for inhibition of the organic cation transport
      (OCT2/MATE1) in the kidney, on the pharmacokinetics of glycopyrronium.
AB  - OBJECTIVE: Glycopyrronium (NVA237), a novel once-daily long-acting muscarinic
      antagonist (LAMA), has recently been approved for maintenance treatment of COPD.
      This study evaluated the effect of organic cation transporter inhibition on
      inhaled glycopyrronium disposition using cimetidine as a probe inhibitor.
      METHODS: In this open-label, two-period, two-sequence, crossover study, 20
      healthy subjects received two treatments. A single dose of 100 MUg glycopyrronium
      was inhaled alone and on Day 4 of a 6-day treatment with oral cimetidine 800 mg
      b.i.d. Trough plasma concentrations of cimetidine were determined throughout
      cimetidine dosing. Plasma concentrations and urinary excretion of glycopyrronium
      were determined up to 72 hours post glycopyrronium dose. The primary
      pharmacokinetics (PK) parameters were plasma peak concentration (Cmax), AUC up to
      the last measured concentration (AUClast), and renal clearance (CLr) of
      glycopyrronium. RESULTS: Cimetidine trough concentrations indicated that PK
      steady state of cimetidine was reached prior to single dose inhalation of
      glycopyrronium. Inhalation of glycopyrronium in the presence of cimetidine
      resulted in an increase in total systemic exposure (AUClast) of glycopyrronium by
      22% (geometric mean ratio 1.22; 90% CI: 1.12 - 1.32). This exposure increase
      correlated with a slight decrease of 23% in CLr (geometric mean ratio 0.77; 90%
      CI: 0.70 - 0.85). Cmax was not affected. Both treatments were safe and well
      tolerated without any deaths or severe adverse events. CONCLUSION: Based on the
      magnitude of the PK changes seen in this study, no relevant drug interaction is
      expected when glycopyrronium is co-administered with cimetidine or other
      inhibitors of the organic cation transport.

PMID- 24040848
TI  - Oral bioavailability of ospemifene improves with food intake.
AB  - OBJECTIVE: To assess the effect of concomitant food intake on the relative
      bioavailability of ospemifene and its main metabolite, 4-hydroxyospemifene, after
      single oral dosing. METHODS: This was an open-label, randomized, balanced, two
      treatment (fed vs. fasted), two-period, two-sequence cross-over study in 24
      healthy male subjects. Single 60-mg doses of ospemifene were administered without
      food or with a high-fat, high-energy breakfast (860 kcal). In an extension study,
      a single 60-mg dose of ospemifene was given to 12 subjects with a low-fat, light
      breakfast (300 kcal). Additional information was acquired by determining tablet
      dissolution profiles in media which reflected fasted and fed intestinal
      conditions. RESULTS: The AUC0-72 h and Cmax of ospemifene were 2.8- and 3.6-fold
      higher after a high-fat breakfast and 1.9- and 2.3-fold higher after a low-fat
      breakfast when compared with an overnight fast. The variability in both primary
      pharmacokinetic parameters was considerably reduced (by up to 50%) with a meal,
      indicating more consistent absorption of ospemifene with concomitant food intake.
      Dissolution in conditions simulating fed intestinal fluid (high bile acid
      concentration) was increased 3-fold compared with dissolution in simulated fasted
      intestinal fluid. CONCLUSIONS: wood markedly enhanced the extent and
      predictability of ospemifene absorption. The increase in bioavailability was not
      linearly related with the fat content of the meal. In vitro dissolution results
      were consistent with these clinical observations. Administration with food
      enhances and standardizes the oral bioavailability of ospemifene. Thus, it is
      recommended that ospemifene tablets should be taken with food.

PMID- 24040849
TI  - Safety, tolerability, pharmacokinetics and pharmacodynamics of high single
      ascending doses of ticagrelor in healthy volunteers.
AB  - OBJECTIVE: Previous studies have indicated that ticagrelor is well tolerated and
      exhibits linear pharmacokinetics up to doses of 600 mg/day. The safety,
      tolerability, pharmacokinetics and pharmacodynamics (bleeding times and pulmonary
      function tests) of high single-ascending doses of ticagrelor were assessed to
      determine the maximum tolerated dose of ticagrelor. MATERIALS AND METHODS: This
      was a randomized, double-blind, placebo-controlled study. Eight healthy
      volunteers were planned for enrollment in each of 3 dose groups, ticagrelor 900
      mg, 1,260 mg, and 1,620 mg (6 : 2 ratio ticagrelor : placebo). RESULTS: The study
      stopping criteria were met when 3 of the 6 volunteers receiving ticagrelor 1,260
      mg experienced moderate gastrointestinal adverse events (AE); none were observed
      with placebo. One volunteer receiving ticagrelor 1,260 mg had a serious AE -
      sinus arrest, high-grade atrioventricular block, and ventricular escape rhythm
      with syncope - and another volunteer had brief, mild dyspnea. Ticagrelor 900 mg
      was well tolerated. Total exposure to ticagrelor increased dose proportionally.
      Peak plasma concentration (Cmax) for ticagrelor did not increase much, most
      likely due to delayed absorption. There were no relevant changes in respiratory
      parameters. Bleeding times were prolonged in those receiving ticagrelor with
      respect to placebo, with longer bleeding times in volunteers receiving ticagrelor
      1,260 mg than in volunteers receiving 900 mg; no bleeding events were reported.
      CONCLUSION: These results indicate that the maximum tolerated single dose of
      ticagrelor is 900 mg in healthy volunteers.

PMID- 24040850
TI  - Difference between the frequencies of antisecretory drug prescriptions in users
      of buffered vs. enteric-coated low-dose aspirin therapies.
AB  - OBJECTIVE: To provide further insights on the risks of gastrointestinal (GI)
      complications in individuals using low-dose aspirin (LDA), we investigated the
      concomitant use of LDA and antisecretory drugs. Additionally, we examined the
      frequency distributions of prescribing sequences for LDA and antisecretory drugs.
      METHODS: Data from a computerized prescription order entry system was analyzed at
      the National Cerebral and Cardiovascular Center of Japan. LDA use in combination
      with H2-receptor antagonists (H2RAs) and proton pomp inhibitors (PPIs) was
      examined over the period from January 2001 to December 2010. Prescription
      sequence symmetry analyses were used to identify LDA-induced H2RAs or PPIs users.
      RESULTS: In December 2010, PPIs accounted for 9.9% of the prescriptions for
      buffered LDA users and 16.1% of those for enteric-coated LDA users. Incident use
      of PPIs occurred more frequently among enteric-coated LDA users than buffered LDA
      users (17.6% vs. 11.0%, respectively). Prescription sequence symmetry analyses of
      PPI use revealed significant associations with enteric-coated LDA use, resulting
      in adjusted sequence ratios of 1.82 (95%CI, 1.11 - 3.03) and 1.87 (95% CI, 1.26 -
      2.83) at intervals of 182 and 365 days, respectively. Enteric-coated LDA users
      tended to initiate PPI therapy on the same date more frequently than buffered LDA
      users (35.1% vs. 10.8%, respectively). CONCLUSIONS: Our findings do not support
      the notion that entericcoated LDA products confer a lower risk for GI
      complications than buffered formulations, but may conversely imply that the risk
      of GI complications associated with buffered LDA is lower than that of enteric
      coated LDA.

PMID- 24040852
TI  - The effect of ezogabine on the pharmacokinetics of an oral contraceptive agent.
AB  - OBJECTIVES: Ezogabine (EZG) is a potassium-channel opener that has been approved
      as adjunctive treatment for partial-onset seizures in adults with epilepsy. This
      Phase I clinical study evaluated the pharmacokinetics (PK), safety, and
      tolerability of coadministration of EZG and a combined oral contraceptive (OC).
      METHODS: An open-label drug-interaction study was conducted in healthy, female
      volunteers aged 18 - 55 years with regular menstrual cycles. The effects of
      steady-state 750 mg EZG on the PK of a combined OC agent containing 1 mg
      norethindrone and 0.035 mg ethinyl estradiol were evaluated, along with the
      effect of the contraceptive hormones on EZG PK. Safety was evaluated by clinical
      laboratory, vital sign, electrocardiogram, physical examination, and adverse
      event (AE) assessments. RESULTS: Of 30 enrolled volunteers, 25 completed all
      treatments. OC did not affect the PK of EZG. EZG increased norethindrone area
      under the concentration-time curve (AUC) by 28%, with no change in the maximum
      plasma concentration (Cmax). Ethinyl estradiol Cmax was 21% lower with no change
      in AUC. The majority of AEs were mild in severity, with the most commonly
      reported being gastrointestinal disorders and nervous system disorders. No deaths
      or serious AEs were reported in this study. Five volunteers discontinued
      treatment due to AEs. CONCLUSIONS: EZG did not have any clinically relevant
      impact on exposure of OC hormones in this study, and the OC hormones did not
      alter EZG PK parameters. This study provides PK evidence that doses of EZG and
      OCs do not need to be altered when co-administered.

PMID- 24040851
TI  - One year long-term study on abuse liability of nalfurafine in hemodialysis
      patients.
AB  - Nalfurafine (nalfurafine hydrochloride, TRK-820, Remitch(r)) was launched as an
      anti-pruritic for uremic pruritus in hemodialysis patients in Japan in 2009.
      Since the drug is an opioid that mainly binds to kappa-receptors and possesses
      kappa-agonistic pharmacological properties and also binds partially, but very
      weakly, to MU-receptors, the abuse liability of the drug was assessed by using
      questionnaires in patients enrolled in a clinical trial evaluating the efficacy
      and safety of the drug. The clinical trial was conducted for up to 52 weeks in
      patients subjected to regular hemodialysis. End-stage renal disease (ESRD)
      patients with uremic pruritus (n = 146) were administered nalfurafine 5 MUg
      intravenously after each hemodialysis session. 81 ESRD patients without uremic
      pruritus served as non-treatment controls. All pruritus patients answered the 3
      questionnaires of "the Addiction Research Centre Inventory (ARCI)", "modified
      Short Opiate Withdrawal Scale (SOWS)", which provides a range of signs and
      symptoms of opiate withdrawal, and Severity of Dependence Scale (SDS), which
      measures the dependence potential of the drug. The control patients were tested
      with the ARCI and modified SOWS questionnaires. There were no significant
      differences between the nalfurafine group and control group in the ARCI and
      modified SOWS scales. Thus, no evidence of abuse liability was indicated in the
      results. Also, no significant differences in the blood pressure, respiratory
      rate, body temperature and pupil diameter were shown between the two groups. 

PMID- 24040853
TI  - Efficacy of H2 receptor antagonists for prevention of upper gastrointestinal
      bleeding during dual-antiplatelet therapy.
AB  - Proton pump inhibitors (PPI) are frequently used to prevent upper
      gastrointestinal bleeding (UGIB) in patients receiving dual-antiplatelet therapy
      (DAPT) with aspirin and clopidogrel. However, the concomitant therapy of PPI and
      DAPT has been associated with a decreased effect of the antiplatelet drugs and an
      increased risk of major adverse cardiovascular events (MACE). It has been
      suggested that histamine H2 receptor antagonists (H2RA) can be used as
      alternatives to PPI to prevent UGIB during DAPT without an increase in the risk
      of MACE. We tested this hypothesis in a retrospective cohort study including
      patients without a prior history of upper gastrointestinal events. We examined
      the incidence of UGIB and MACE in 296 patients treated with H2RA (H2RA group) and
      447 patients not treated with H2RA (control group) during DAPT with aspirin and
      clopidogrel after drug-eluting stent implantation. The patients treated with PPI
      were excluded. In the 1-year follow-up, UGIB occurred in 2 patients (0.7%) in the
      H2RA group and 12 (2.7%) in the control group. The incidence of UGIB was
      significantly different between the two groups (p = 0.049 in log-rank test). MACE
      occurred in 31 patients (10.5%) in the H2RA group and in 54 patients (12.1%) in
      the control group, and the incidence was not significantly different (p = 0.447
      in logrank test). Thus, H2RA may be effective safe alternatives to PPI during
      DAPT in patients without a prior history of upper gastrointestinal events. 

PMID- 24040854
TI  - The bone evaluation study (BEST): patient care and persistence to treatment of
      osteoporosis in Germany.
AB  - OBJECTIVE: Data on fracture frequency and medical care of patients with
      osteoporosis are still insufficient. We aimed to analyze frequency of
      osteoporosis-related fractures and multiple fractures, re-fracture rates,
      treatment prevalence, and persistence to osteoporosis-related medication in
      Germany. METHODS AND MATERIALS: Using claims data of a state health insurer (2006
      - 2009), we performed a retrospective "real world" analysis. Inclusion criteria
      were age of 50 years or older and an osteoporosis diagnosis or a prescription for
      defined osteoporosis-related medication. We assessed fractures, frequencies, and
      the number of multiple fractures per patient as well as time to follow-up
      fracture and drug persistence using Kaplan-Meier analysis. RESULTS: Within the
      observation period, 27% of the osteoporosis patients sustained fractures; of
      those with fractures, 69% had multiple fractures. For patients with multiple
      fractures, re-fracture rate after 360 days was between 69% for patients who
      received parathyroid hormone and 85% for patients who received no anti
      osteoporotic medication 360 days before follow-up fracture. In the patient
      population, persistence rates after 1 year were between 58% for parathyroid
      hormone and 2% for other osteoporosis-specific drugs (alfacalcidol, fluorides,
      nandrolone, calcitonin). CONCLUSIONS: In Germany, the number of patients with
      osteoporosis-attributable fractures is high. There are still deficits in proper
      treatment as well as in drug persistence. Low persistence lead to a relatively
      high proportion of patients with follow-up fractures.

PMID- 24040855
TI  - The role of multidrug resistance-1 (MDR1) variants in response to fexofenadine
      among Jordanians.
AB  - OBJECTIVE: The MDR1 gene encodes for P-glycoprotein (P-gp), which is an efflux
      transporter at the cell membrane. The P-gp has wide substrate specificity for
      multiple medications, including the antiallergic drug fexofenadine. In this
      study, we investigated the possible association between three common MDR1 gene
      polymorphisms (G2677T, C3435T, and C1236T), and the anti-allergic effect of
      fexofenadine among Jordanians. MATERIALS AND METHODS: An assessment of the
      severity of allergic rhinitis symptoms was performed for all patients (n = 260)
      pre- and 7 days into fexofenadine. MDR1 polymorphisms were genotyped using
      polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP).
      RESULTS: Relative to baseline, fexofenadine treatment was associated with
      significant reduction in allergic individual and total scores (p < 0.0001). Male
      gender was associated with less mean reduction in total allergic rhinitis
      symptoms score than in female (p < 0.05). In multivariate analysis, male gender
      was negatively correlated with response to fexofenadine (p = 0.01). The MDR1 gene
      C1236T polymorphism showed significant correlation with changes in total symptoms
      score from baseline in males (p < 0.05) but not in females. No significant
      correlation between fexofenadine response parameters and G2677T or the C3435T
      polymorphism was observed. CONCLUSIONS: The MDR1 gene polymorphism C1236T was
      associated with the anti-allergic effect of fexofenadine among male Jordanians.

PMID- 24040856
TI  - Influence of phenylephrine or ephedrine on maternal hemodynamics upon umbilical
      cord clamping during cesarean delivery.
AB  - BACKGROUND AND OBJECTIVE: Vasopressors ephedrine and phenylephrine are commonly
      used with spinal anesthesia during cesarean delivery. Studies on them have
      focused on the period before the umbilical cord is clamped, although anesthesia
      is continuously administered throughout and after this event. This study aimed to
      compare the effects of these drugs on maternal hemodynamics at and after clamping
      of the umbilical cord. STUDY DESIGN: Prospective, randomized, double-blind study.
      SETTING: Parturients (n = 60) scheduled for elective cesarean delivery were
      randomly divided into an ephedrine group and a phenylephrine group. Each woman
      received an intrathecal injection of bupivacaine (7.5 mg). MEASUREMENTS: Patients
      in the ephedrine and phenylephrine groups were infused continuously with
      ephedrine (0.02 mg*kg-1*min-1) or phenylephrine (0.25 MUg*kg-1*min-1),
      respectively, from immediately after the injection of bupivacaine until
      termination 10 minutes after the umbilical cord was clamped (the endpoint).
      Hemodynamic changes were recorded. RESULTS: After clamping the umbilical cord,
      the patients who were administered ephedrine experienced significant increases in
      heart rate (89 +/- 11 beats/min to 106 +/- 15 beats/min), cardiac output (6.4 +/-
      0.9 l/min to 7.6 +/- 1.2 l/min) and cardiac index (3.5 +/- 0.39 l*min-1*m-2 to
      4.3 +/- 0.48 l*min-1*m-2), while the systemic vascular resistance decreased (908
      +/- 296 dyne.s/cm5 to 711 +/- 285 dyne.s/cm5). Such differences were not observed
      in the patients who received phenylephrine. Moreover, the heart rate of patients
      administered ephedrine was higher than that of patients given phenylephrine after
      clamping the umbilical cord. CONCLUSION: Continuous infusion of phenylephrine
      during cesarean delivery maintains a stable maternal hemodynamic status better
      than ephedrine.

PMID- 24040858
TI  - Regio- and diastereoselective stepwise [8 + 3]-Cycloaddition reaction between
      tropone derivatives and donor-acceptor cyclopropanes.
AB  - A novel SnCl4-catalyzed [8 + 3]-cycloaddition reaction between tropone
      derivatives and donor-acceptor aminocyclopropanes is described. The process leads
      to the formation of amino-substituted tetrahydrocyclohepta[b]pyrans with complete
      regio- and diastereoselectivity. Density functional theory calculations suggest
      that the cycloaddition occurs stepwise through an aromatic zwitterionic
      intermediate. 

PMID- 24040857
TI  - Circulating microRNA expression profile and systemic right ventricular function
      in adults after atrial switch operation for complete transposition of the great
      arteries.
AB  - BACKGROUND: Data on the use of circulating microRNAs (miRNAs) as biomarkers of
      cardiovascular diseases are emerging. Little, however, is known on the expression
      profile of circulating of microRNAs in congenital heart malformations with a
      systemic right ventricle that is prone to functional impairment. We aimed to test
      the hypothesis that circulating miRNA profile is altered in patients late after
      atrial switch operation for complete transposition of the great arteries (TGA)
      and further explored possible relationships between alteration of circulating
      miRNAs and systemic ventricular contractility. METHODS: Circulating miRNA
      expression profiling of serum samples from 5 patients and 5 healthy controls was
      performed. The results were validated in 26 patients and 20 controls using real
      time quantitative reverse-transcription polymerase chain reaction for candidate
      miRNAs with fold changes >3 by expression profiling. Systemic ventricular
      myocardial acceleration during isovolumic contraction (IVA) was determined by
      colour tissue Doppler echocardiography. RESULTS: Compared with controls, patients
      had significantly lower systemic ventricular IVA (p = 0.002). Of the 23
      upregulated miRNAs identified by profiling, 11 were validated to be increased in
      patients compared with controls: miR-16, miR-106a, miR-144*, miR-18a, miR-25, miR
      451, miR-486-3p, miR-486-5p, miR-505*, let-7e and miR-93. Among the validated 11
      miRNAs, miR-18a (r = -0.45, p = 0.002) and miR-486-5p (r = -0.35, p = 0.018)
      correlated negatively with systemic ventricular IVA for the whole cohort.
      CONCLUSIONS: A distinct serum miRNA expression signature exists in adults with
      complete TGA after atrial switch operation, with serum miR-18a and miR-486-5p
      being associated with systemic ventricular contractility.

PMID- 24040859
TI  - Bismuth-doped tin oxide-coated carbon nanotube network: improved anode stability
      and efficiency for flow-through organic electrooxidation.
AB  - In this study, a binder-free, porous, and conductive 3D carbon-nanotube (CNT)
      network uniformly coated with bismuth-doped tin oxide (BTO) nanoparticles was
      prepared via a simple electrosorption-hydrothermal method and utilized for the
      electrooxidative filtration of organics. The BTO-CNT nanocomposite was
      characterized by scanning electron microscopy, thermogravimetric analysis,
      transmission electron microscopy, X-ray photoelectron spectroscopy, linear sweep
      voltammetry, and Tafel analysis. The submonolayer BTO coating is composed of
      3.9+/-1.5 nm diameter nanoparticles (NPs). The oxygen-evolution potential of the
      BTO-CNT nanocomposite was determined to be 1.71 V (vs Ag/AgCl), which is 440 mV
      higher than an uncoated CNT anode. Anodic stability, characterized by CNT
      oxidative corrosion to form dissolved species, indicated that the BTO-CNT
      incurred negligible corrosion up to Vanode=2.2 V, whereas the uncoated CNT was
      compromised at Vanode>=1.4 V. The effect of metal oxide-nanoparticle coating on
      anodic performance was initially studied by oxalate oxidation followed by total
      organic carbon (TOC) and chemical oxygen demand (COD) analysis. The BTO-CNT
      displayed the best performance, with ~98% oxalate oxidation (1.2 s filter
      residence time) and current efficiencies in the range of 32 to >99%. The BTO-CNT
      anode energy consumption was 25.7 kW h kgCOD(-1) at ~93% TOC removal and 8.6 kW h
      kgCOD(-1) at ~50% TOC removal, comparable to state-of-the-art oxalate oxidation
      processes (22.5-81.7 kW h kgCOD(-1)). The improved reactivity, current
      efficiency, and energy consumption are attributed to the increased conductivity,
      oxygen-evolution potential, and stability of the BTO-CNT anode. The effectiveness
      and efficiency of the BTO-CNT anode as compared to the uncoated CNT was further
      investigated by the electrooxidative filtration of ethanol, methanol,
      formaldehyde, and formate, and it was determined to have TOC removals 2 to 8
      times greater, mineralization current efficiencies 1.5 to 3.5 times greater, and
      energy consumption 4 to 5 times less than the uncoated CNT anode.
      Electrooxidation and anode passivation mechanisms are discussed.

PMID- 24040861
TI  - Organocatalyzed three-component Ugi and Passerini reactions of 4-oxoazetidine-2
      carbaldehydes and azetidine-2,3-diones. Application to the synthesis of gamma
      lactams and gamma-lactones.
AB  - The organocatalyzed U-3CR of 4-oxoazetidine-2-carbaldehydes has been studied. In
      addition, the organocatalyzed P-3CR of 4-oxoazetidine-2-carbaldehydes and
      azetidine-2,3-diones has been described for the first time. U-3CR and P-3CR
      adducts have been obtained in good yields and reasonable diastereoselectivities.
      Phenyl phosphinic acid has been the catalyst of choice to study the scope of both
      organocatalyzed multicomponent reactions using a variety of beta-lactams,
      isocyanides, and amines. Highly functionalized U-3CR and P-3CR adducts derived
      from beta-lactams have proved to be useful substrates for the preparation of
      enantiopure gamma-lactams and gamma-lactones via N1-C2 beta-lactam ring
      opening/cyclization under acidic or basic conditions. 

PMID- 24040860
TI  - Buschke-Lowenstein tumor with squamous cell carcinoma treated with chemo
      radiation therapy and local surgical excision: report of three cases.
AB  - Treatment of anorectal Buschke-Lowenstein tumor (BLT) with squamous cell
      carcinoma (SCC) transformation is not univocal given the rarity of the disease.
      BLT is characterized by its large size and tendency to infiltrate into underlying
      tissues. Malignant transformation can occur and it is important to identify the
      presence of neoplastic foci to decide the proper treatment. Our aim was to assess
      the effectiveness of neo-adjuvant chemo-radiation therapy (CRT) and local
      excision in order to avoid abdomino-perineal resection (APR). Three cases of
      anorectal BLT with SCC transformation are presented. All patients were HIV
      positive and treated with antiretroviral drugs. They underwent preoperative
      endoanal ultrasound, biopsies, total body tomography and anal brushing. Treatment
      consisted of neo-adjuvant chemo-radiation therapy (45 Gy to the pelvis plus a
      boost with 14.40 Gy to the primary tumor for a total of 59.40 Gy, and mitomycin-C
      in bolus on the first day, plus 5-fluorouracil by continuous infusion in the
      first and in the sixth week) and subsequent local surgical excision. During the
      follow-up, patients were subjected to the same preoperative diagnostic
      investigations and high resolution anoscopy. All patients showed a complete
      regression of the lesion after CRT and were treated by local surgical excision,
      thus avoiding permanent colostomy. In conclusion neo-adjuvant chemo-radiation
      therapy with local surgical excision could be considered an effective therapy in
      the treatment of anorectal BLT with SCC transformation to avoid APR. 

PMID- 24040862
TI  - Single-tablet regimens in HIV: does it really make a difference?
AB  - OBJECTIVES: Review of the available data on the currently available single-tablet
      regimens (STRs), from the analysis of efficacy and safety to the key points of
      value in terms of adherence, quality of life and pharmacoeconomic evaluation.
      METHODS: For this narrative review, literature searches have been performed in
      PubMed, IndexRevMed and Cochrane, using the search terms HIV, single-tablet, one
      pill, single dose, fixed-dose, and STR. These have been reviewed and complemented
      with the most recent publications of interest. RESULTS: Fixed-dose combinations
      are a significant advance in antiretroviral treatment simplification,
      contributing to an increase in compliance with complex chronic therapies, thus
      improving patients' quality of life. Reducing the number of pills and daily doses
      is associated with higher adherence and better quality of life. As a fixed-dose
      combination tablet given once daily, EFV/FTC/TDF was the first available STR
      combining efficacy, tolerability and convenience, with the simplest dosing
      schedule and smallest numbers of pills of any ART combination therapy. The
      RPV/FTC/TDF is a next-generation NNRTI-based STR, a once daily complete ART
      regimen for the treatment of HIV-1 infection. Recently the combination of
      EVG/COBI/FTC/TDF was also approved by the European Commission, and is the first
      integrase inhibitor-based STR. Receiving antiretroviral therapy as once daily STR
      is associated with both clinical and economic benefits, which confirms previous
      research. CONCLUSIONS: The associated benefits of STRs provide a valid strategy
      for the treatment of HIV-infected patients.

PMID- 24040863
TI  - Toxic mechanisms of 3-monochloropropane-1,2-diol on progesterone production in
      R2C rat leydig cells.
AB  - 3-Monochloropropane-1,2-diol (3-MCPD) is a well-known food processing contaminant
      that has been shown to impede the male reproductive function. However, its
      mechanism of action remains to be elucidated. In this study, the effects of 3
      MCPD on progesterone production were investigated using R2C Leydig cells. 3-MCPD
      caused concentration-dependent inhibition of cell viability at the IC25, IC50,
      and IC75 levels of 1.027, 1.802, and 3.160 mM, respectively. Single cell
      gel/comet assay and atomic force microscopy assay showed that 3-MCPD
      significantly induced early apoptosis. In addition, 3-MCPD significantly reduced
      progesterone production by reducing the expression of cytochrome P450 side-chain
      cleavage enzyme, steroidogenic acute regulatory protein, and 3beta-hydroxysteroid
      dehydrogenase in R2C cells. The change in steroidogenic acute regulatory protein
      expression was highly consistent with progesterone production. Furthermore, the
      mitochondrial membrane potential and cAMP significantly decreased. 

PMID- 24040864
TI  - Can we trust measures of healthcare utilization from household surveys?
AB  - BACKGROUND: The research community relies heavily on measures of healthcare
      utilization from household surveys to understand health seeking choices and to
      evaluate interventions in developing countries. Such measures are known to suffer
      from recall problems but there is limited evidence of whether the method of data
      collection affects evaluation findings. We compared the results of a randomized
      trial of free healthcare using utilization data from two sources. METHODS: Data
      are from a study in Ghana, in which 2,194 households containing 2,592 children
      under 5 y old were randomized into a prepayment scheme providing free primary and
      some referral care, or to a control group whose families paid user fees for
      healthcare. Data on morbidity and health seeking behaviour were collected using a
      standard household survey administered at endline and a pictorial diary given to
      households over a six month period, collected at monthly intervals. RESULTS: Self
      reported measures of morbidity and healthcare utilization were substantially
      lower in the household survey than the pictorial diary when the recall period was
      over a month. Introducing free healthcare had a positive effect on primary care
      visits based on the pictorial diary and a non-significant negative effect
      according to the household survey. Using any clinic visit in the past month as
      the outcome, the difference in the effect of free care between the two data
      collection methods was 3.6 percentage points (p = 0.078). CONCLUSIONS: The
      findings raise methodological concerns about measures of healthcare utilization
      from household surveys, particularly in the evaluation of health financing
      interventions.

PMID- 24040865
TI  - Quantitative analysis of tumor shrinkage due to chemotherapy and its implication
      for radiation treatment planning in limited-stage small-cell lung cancer.
AB  - BACKGROUND: The optimal timing of chemoradiotherapy in limited-stage small-cell
      lung cancer (LS-SCLC) hasn't been established, although evidence from studies
      supported that patients can benefit from early radiation therapy. The purpose of
      this study was to quantify tumor shrinkage in response to induction chemotherapy
      (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters
      and determine its implication for the timing of radiation therapy for patients
      with LS-SCLC. METHODS: Twenty patients with LS-SCLC who were treated with IC
      followed by concomitant radiation therapy were investigated retrospectively. Ten
      patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC
      CT imaging was coregistered with a simulation CT, and virtual radiation plans
      were created for pre- and post-IC thoracic disease in each case. The changes in
      the gross target volume (GTV), planning target volume (PTV) and dosimetric
      factors associated with the lungs, esophagus and heart were analyzed. RESULTS:
      The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%,
      respectively, which resulted in a significant reduction in the radiation exposure
      to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of
      normal tissue were not significantly affected by the number of chemotherapy
      cycles delivered, although patients who received 2 cycles of IC had a greater
      decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p =
      0.273). CONCLUSIONS: Our data showed that targeting the tumor post-IC may reduce
      the radiation dose to normal tissue in patients with LS-SCLC. However, the
      benefit to the normal tissue was not increased by an additional cycle of IC.
      These findings suggest that the first cycle of chemotherapy is very important for
      tumor shrinkage and that initiating thoracic radiation therapy at the second
      cycle of chemotherapy may be a reasonable strategy for timing of radiation
      therapy in LS-SCLC treatment.

PMID- 24040866
TI  - Nose-to-brain transport of aerosolised quantum dots following acute exposure.
AB  - Nanoparticles are of wide interest due to their potential use for diverse
      commercial applications. Quantum dots (QDs) are semiconductor nanocrystals
      possessing unique optical and electrical properties. Although QDs are commonly
      made of cadmium, a metal known to have neurological effects, potential transport
      of QDs directly to the brain has not been assessed. This study evaluated whether
      QDs (CdSe/ZnS nanocrystals) could be transported from the olfactory tract to the
      brain via inhalation. Adult C57BL/6 mice were exposed to an aerosol of QDs for 1
      h via nasal inhalation, and nanoparticles were detected 3 h post-exposure within
      the olfactory tract and olfactory bulb by a wide range of techniques, including
      visualisation via fluorescent and transmission electron microscopy. We conclude
      that, following short-term inhalation of solid QD nanoparticles, there is rapid
      olfactory uptake and axonal transport to the brain/olfactory bulb with observed
      activation of microglial cells, indicating a pro-inflammatory response. To our
      knowledge, this is the first study to clearly demonstrate that QDs can be rapidly
      transported from the nose to the brain by olfactory uptake via axonal transport
      following inhalation.

PMID- 24040868
TI  - Confronting the residual cardiovascular risk beyond statins: the role of
      fibrates, omega-3 fatty acids, or niacin, in diabetic patients.
AB  - Diabetics are regarded a special category of patients known to experience higher
      rates of cardiovascular complications as compared to the non-diabetic ones.
      Despite substantial efforts to minimize these risks, with aggressive antiplatelet
      and lipid lowering therapy, some of the diabetic patients still have a
      considerable residual risk for cardiovascular adverse events. Important
      preclinical data with potent lipid-lowering agents, like fibrates, omega-3-fatty
      acids, and niacin, have shown that they can provide sufficient help in reducing
      rates of cardiovascular events. In the present review, we are aim to explain
      their basic mechanisms of action, to present all the available clinical data
      regarding the efficacy of those agents, and to identify specific diabetic
      patients' subsets, in whom supplementary therapy with those agents could provide
      substantial benefit in terms of clinical outcome and not only lipid profile
      improvement. 

PMID- 24040869
TI  - Standard and emerging treatment options for diabetic neuropathy.
AB  - Diabetic neuropathy is a common complication of diabetes mellitus affecting 30
      50% of patients and is a major cause for increased costs, morbidity and
      mortality. Strict diabetes control prevents this complication and may restore
      neurologic deficits in the early stages. Several efforts have been undertaken to
      alter the natural history of this complication, including the use of aldose
      reductase and protein kinase-C inhibitors, as well as antioxidants. Available
      data so far do not support the use of aldose reductase inhibitors due to safety
      issues and efficacy. Protein kinase-C inhibitors have provided encouraging
      initial results but their development has been halted. Antioxidants, like a
      lipoic acid, improve some neurological deficits and painful symptoms. There are
      effective and safe medications such as anticonvulsants, antidepressants and
      opioids for the management of patients with painful symptoms. In this revew we
      present standard and emerging treatment modalities for the etiologic and
      symptomatic treatment of diabetic neuropathy. 

PMID- 24040867
TI  - Linking neural activity to complex decisions.
AB  - In the 1990s, seminal work from Newsome and colleagues made it possible to study
      the neuronal mechanisms of simple perceptual decisions. The key strength of this
      work was the clear and direct link between neuronal activity and choice
      processes. Since then, a great deal of research has extended these initial
      discoveries to more complex forms of decision making, with the goal of bringing
      the same strength of linkage between neural and psychological processes. Here, we
      discuss the progress of two such research programs, namely our own, that are
      aimed at understanding memory-guided decisions and reward-guided decisions. These
      problems differ in the relevant brain areas, in the progress that has been
      achieved, and in the extent of broader understanding achieved so far. However,
      they are unified by the use of theoretical insights about how to link neuronal
      activity to decisions. 

PMID- 24040870
TI  - Editorial: Dietary habits, pharmacogenomics and treatment of diabetes and its
      complications: where do we stand?

PMID- 24040871
TI  - Statins and new-onset diabetes.
AB  - Statins are highly efficacious lipid modifying agents that reduce the risk for
      cardiovascular (CV) events in both primary and secondary prevention settings.
      However, statins affect molecular mechanisms which adversely impact on insulin
      sensitivity and beta-cell function, thereby increasing risk for new onset
      diabetes mellitus (NOD). Defining the mechanisms involved is the focus of
      considerable current investigation. The statins reduce the risk for CV events in
      normoglycemic patients as well as in those with diabetes mellitus (DM) and their
      benefits outweigh the risk of inducing NOD. We review the clinical evidence for
      NOD with statin treatment, as well as the potential mechanisms involved. Our
      literature search was based on PubMed and Scopus listings. Further large studies
      are needed to elucidate both the association between NOD and statin use and the
      underlying mechanisms. 

PMID- 24040872
TI  - Sodium-glucose co-transporter 2 inhibition in diabetes treatment: current
      evidence and future perspectives.
AB  - Sodium-glucose co-transporters (SGLT2) are mainly expressed in the kidneys and
      are responsible for the renal handling of glucose load. SGLT2 inhibitors
      represent the latest oral agents for diabetes treatment. Their unique mechanism
      of action, which practically spares the insulin secretion or insulin utilization,
      differentiates the SGLT2 inhibitors from any existing antidiabetic agent. Thus,
      it is hypothesized that SGLT2 inhibitors can be effectively (and probably safely)
      combined with any existing antidiabetic agent (including insulin), either as
      monotherapy, or in dual or triple combinations. All these hypotheses are
      currently tested in many clinical trials. Currently dapagliflozin, one of the
      three most advanced SGLT2 inhibitors in the development (along with canagliflozin
      and empagliflozin), is already in the market in few European countries and
      canagliflozin has been approved from the Food and Drug Administration (FDA) in
      US. The evidence so far shows that SGLT2 inhibitors are equally effective to
      established antidiabetic agents such as metformin or sulfonylureas in their
      ability to lower HbA1c. On the other hand, SGLT2 inhibitors increase the
      possibility of genitourinary infections in type 2 diabetic individuals. Their
      potency in different populations and with different background therapy, but more
      importantly their short and long term safety remains to be seen. 

PMID- 24040873
TI  - The role of oral antidiabetic agents and incretin mimetics in type 2 diabetic
      patients with non-alcoholic fatty liver disease.
AB  - The aim of this review is to examine the evidence on the role of antidiabetic
      agents in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic fatty
      liver disease (NAFLD). In particular, metformin does not seem to have significant
      effects on liver histology. Glitazones improve steatosis and necro-inflammation,
      delay progression of fibrosis, and ameliorate glucose and lipid metabolism and
      subclinical inflammation. However, there is now evidence that prolonged treatment
      with these agents may offer no additional histological benefit and that metabolic
      improvement does not necessarily parallel histological improvement. Moreover, the
      long-term safety and efficacy of glitazones is an issue of continuing concern.
      Injectable glucagon-like peptide 1 (GLP-1) agonists and dipeptidyl peptidase 4
      (DPP-4) inhibitors are more recent antidiabetic agents with some promising
      preliminary resulst in NFLD. However, experience with their use is still very
      limited. In conclusion, no antidiabetic agent has hitherto been shown to exert a
      beneficial effect on hepatic fibrosis. However, pharmacological treatment could
      be considered in patients with non-alcoholic steatohepatitis (NASH) not
      responding to lifestyle intervention. Finally, larger long-term studies are
      needed to shed more light on the effect of antidiabetic treatment on NAFLD. 

PMID- 24040874
TI  - The genetic architecture of type 2 diabetes pharmacotherapy: the emerging genomic
      evidence.
AB  - Response to anti-diabetic medications is not always predictable or favourable
      even in phenotypically similar type-2 diabetes (T2D) cases. This is not only due
      to patient's compliance and access to care but is also considered to be an effect
      of idiosyncratic differences among individuals, stemming from the combination of
      their unique genetic background and environmental exposures. In this systematic
      review, we aimed to summarise the available evidence on pharmacogenetic and
      pharmacogenomic studies of oral agents for T2D that are currently in the market
      and describe the agents studied, the targeted loci in regards to the efficacy and
      the toxicity profile of the agents included. We included 53 studies published
      between 2003-2012, which examined the following anti-diabetic classes:
      sulphonylureas, metformin, metiglinides and thiazolidenediones. There were no
      published studies on newer agents (e.g. incretin based treatments). Forty-nine
      studies (92.5%) examined the therapeutic response to oral antiglycaemic agents.
      Outcomes assessed included changes in metabolic markers (fasting or postprandial
      blood glucose, fasting or postprandial insulin, HbA1c), Homeostasis Assessment
      Model (HOMA)-Insulin Resistance (IR) or HOMA-B-cell function (HOMA-B), and time
      to monotherapy failure. Regarding side effects, hypoglycaemia and TZD-related
      oedema were the most commonly assessed. In the vast majority of the studies
      included (n=38, 71.7%), more than one outcomes (n=27, 50.9%) and/or more than one
      SNPs (n=21, 39.6%) were evaluated in the same publication, but most studies
      examined one drug (n=50, 94.3%). A considerable number of the proposed genes seem
      to be related to beta-cell development and function, but there are several genes
      whose underlying pathway linked to diabetes pharmacotherapy remains poorly
      understood. Pharmacogenomics are still not in pace with the wealth of information
      provided by GWAS in the genetics of T2D and related traits and the proposed
      associations need further validation in well-characterized large studies of
      varying ancestral origins. 

PMID- 24040875
TI  - The role of statins in the treatment of type 2 diabetes mellitus: an update.
AB  - The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM
      is associated with both microvascular (neuropathy, nephropathy and retinopathy)
      and macrovascular complications [coronary artery disease (CAD), stroke, carotid
      artery disease and peripheral artery disease (PAD)]. Apart from acting on
      diabetic dyslipidemia, statins were shown to exert beneficial effects on several
      diabetic complications as well as other cardiovascular (CVD) risk predictors such
      as endothelial dysfunction, inflammation, oxidative stress, chronic kidney
      disease (CKD), non-alcoholic fatty liver disease (NAFLD), metabolic syndrome
      (MetS), obstructive sleep apnea syndrome (OSAS) and hyperuricemia. Several
      clinical trials involving T2DM patients have reported significant reductions in
      coronary and cerebrovascular events following statin treatment. However, a modest
      statin-related risk of new-onset diabetes (NOD) has been reported but that did
      not [corrected] outweigh the benefit of CVD risk reduction in high-risk
      individuals. Overall, statin use is beneficial and should be recommended in
      diabetic patients to target their increased CVD risk.

PMID- 24040876
TI  - Bariatric surgery as metabolic surgery for diabetic patients.
AB  - The recent increase in the prevalence of obesity seems to be responsible for the
      increase in T2 Diabetes Mellitus (T2DM). At present around 50 % of T2DM patients
      are obese and this percentage appears set to increase in the near future.
      Successful management of T2DM in obese patients is a complicated task, as many
      parameters such as blood pressure, LDL-cholesterol levels have to be adequately
      controlled along with HbA1c levels. There is a substantial amount of evidence
      showing that bariatric surgery achieves long term remission of diabetes in the
      majority of obese patients and improves significantly comorbidities associated
      with DM such as dyslipidemia, hypertension, and obstructive sleep apnea. It seems
      that early surgical intervention before irreversible b-cell damage has occurred,
      increases the chances of long term T2DM resolution. However, at present a very
      small percentage (< 2%) of obese patients with T2DM is treated surgically. The
      present review focuses on the efficacy and safety of the main bariatric
      procedures. It also emphasizes the mechanism with which bariatric surgery exerts
      its therapeutic effect and on the long term results on T2DM remission. 

PMID- 24040877
TI  - Glycemic index, glycemic control and beyond.
AB  - It is currently estimated that over 370 million individuals have diabetes, making
      diabetes a major public health issue contributing significantly to global
      morbidity and mortality. The steep rise in diabetes prevalence over the past
      decades is attributable, in a large part, to lifestyle changes, with dietary
      habits and behaviour as significant contributors. Despite the relatively wide
      availability of antidiabetic medicine, it is lifestyle approaches that still
      remain the cornerstone of diabetes prevention and treatment. Glycemic index (GI)
      is a nutritional tool which represents the glycemic response to carbohydrate
      ingestion. In light of the major impact of nutrition on diabetes pathophysiology,
      with the rising need to combat the escalating diabetes epidemic, this review will
      focus on the role of GI in glycemic control, the primary target of diabetic
      treatment and beyond. The review will present the evidence relating GI and
      diabetes treatment and prevention, as well as weight loss, weight maintenance and
      cardiovascular disease risk factors. 

PMID- 24040878
TI  - Patient information in Graves' disease and thyroid-associated ophthalmopathy:
      readability assessment of online resources.
AB  - BACKGROUND: The Internet is a vital source of information for patients hoping to
      learn more about their disease. Health literacy of the general population is
      known to be poor, with the U.S. Department of Health and Human Services (USDHHS)
      recommending that patient-oriented literature be written at a fourth- to sixth
      grade reading level to optimize comprehensibility. In this study we assessed the
      readability of online literature specifically for Graves' disease (GD) and
      thyroid-associated ophthalmopathy (TAO). METHODS: Readability of the content of
      the top 20 English-language GD patient-oriented online resources and top 30 of
      the equivalent TAO resources returned by Google search was analyzed. Web pages
      were identified using the Google search terms "Graves' disease" and "Thyroid
      Associated Ophthalmopathy," respectively. Extraneous text (e.g., hyperlinks,
      affiliations, disclaimers) was removed. Relevant text proceeded to readability
      analysis using four validated measures: Flesch Reading Ease Score, Flesch-Kincaid
      Grade Level, Simple Measure of Gobbledygook, and Gunning-Fog Index. Readability
      was compared with USDHHS standards. RESULTS: Overall, median word count (with
      interquartile range [IQR] and range) was 990 (IQR 846, 195-3867), with a median
      of 18 words per sentence (IQR 4.0, 7.5-28). Median Flesch Reading Ease Score was
      46 (IQR 13, 24-64), Flesch-Kincaid Grade Level 11 (IQR 3.0, 7.2-17), Simple
      Measure of Gobbledygook 13 (IQR 2.0, 9.6-17), and Gunning-Fog Index 13 (IQR 3.0,
      9.2-19), each equivalent to a reading level of >11th grade and "difficult" on the
      USDHHS classification. None of the web pages evaluated had readability scores in
      accordance with published guidelines. There was no significant difference with
      the country of origin of each web page, website commercial status, or with pages
      predominantly focused on GD or TAO. CONCLUSIONS: Readability scores for online GD
      and TAO patient-focused materials are inferior to those recommended. Screening of
      this online material, as well as subsequent revision, is crucial to increase
      future patient knowledge, satisfaction, and compliance.

PMID- 24040880
TI  - Heterogeneity and event dependence in the analysis of sickness absence.
AB  - BACKGROUND: Sickness absence (SA) is an important social, economic and public
      health issue. Identifying and understanding the determinants, whether biological,
      regulatory or, health services-related, of variability in SA duration is
      essential for better management of SA. The conditional frailty model (CFM) is
      useful when repeated SA events occur within the same individual, as it allows
      simultaneous analysis of event dependence and heterogeneity due to unknown,
      unmeasured, or unmeasurable factors. However, its use may encounter computational
      limitations when applied to very large data sets, as may frequently occur in the
      analysis of SA duration. METHODS: To overcome the computational issue, we propose
      a Poisson-based conditional frailty model (CFPM) for repeated SA events that
      accounts for both event dependence and heterogeneity. To demonstrate the
      usefulness of the model proposed in the SA duration context, we used data from
      all non-work-related SA episodes that occurred in Catalonia (Spain) in 2007,
      initiated by either a diagnosis of neoplasm or mental and behavioral disorders.
      RESULTS: As expected, the CFPM results were very similar to those of the CFM for
      both diagnosis groups. The CPU time for the CFPM was substantially shorter than
      the CFM. CONCLUSIONS: The CFPM is an suitable alternative to the CFM in survival
      analysis with recurrent events, especially with large databases.

PMID- 24040883
TI  - What do love and jealousy taste like?
AB  - Metaphorical expressions linking love and jealousy to sweet, sour, and bitter
      tastes are common in normal language use and suggest that these emotions may
      influence perceptual taste judgments. Hence, we investigated whether the
      phenomenological experiences of love and jealousy are embodied in the taste
      sensations of sweetness, sourness, and bitterness. Studies 1A and 1B validated
      that these metaphors are widely endorsed. In three subsequent studies,
      participants induced to feel love rated a variety of tastants (sweet-sour candy,
      bitter-sweet chocolates, and distilled water) as sweeter than those who were
      induced to feel jealous, neutral, or happy. However, those induced to feel
      jealous did not differ from those induced to feel happy or neutral on bitter and
      sour ratings. These findings imply that emotions can influence basic perceptual
      judgments, but metaphors that refer to the body do not necessarily influence
      perceptual judgments the way they imply. We further suggest that future research
      in metaphoric social cognition and metaphor theory may benefit from investigating
      how such metaphors could have originated.

PMID- 24040879
TI  - Resting state EEG abnormalities in autism spectrum disorders.
AB  - Autism spectrum disorders (ASD) are a group of complex and heterogeneous
      developmental disorders involving multiple neural system dysfunctions. In an
      effort to understand neurophysiological substrates, identify
      etiopathophysiologically distinct subgroups of patients, and track outcomes of
      novel treatments with translational biomarkers, EEG (electroencephalography)
      studies offer a promising research strategy in ASD. Resting-state EEG studies of
      ASD suggest a U-shaped profile of electrophysiological power alterations, with
      excessive power in low-frequency and high-frequency bands, abnormal functional
      connectivity, and enhanced power in the left hemisphere of the brain. In this
      review, we provide a summary of recent findings, discuss limitations in available
      research that may contribute to inconsistencies in the literature, and offer
      suggestions for future research in this area for advancing the understanding of
      ASD. 

PMID- 24040881
TI  - Serotonin transporter genotype (5-HTTLPR) and electrocortical responses
      indicating the sensitivity to negative emotional cues.
AB  - Growing literature indicates that emotional reactivity and regulation are
      strongly linked to genetic modulation of serotonergic neurotransmission. However,
      until now, most studies have focused on the relationship between genotypic
      markers, in particular the serotonin transporter-linked polymorphic region (5
      HTTLPR), and neural structures using MRI. The current study aimed to bridge the
      gap between the relevant MRI literature on the effects of the 5-HTTLPR genotype
      and the research tradition focusing on transient lateralized changes of
      electrocortical activity in the prefrontal cortex using electroencephalography
      (EEG). Lateral shifts of EEG alpha asymmetry in response to an aversive film
      consisting of scenes of real injury and death were assessed in healthy
      participants (n = 165). To evaluate the specificity of the 5-HTTLPR effect,
      participants were also tested for the COMT Val158Met polymorphism which is linked
      to dopamine inactivation. While viewing the film, individuals homozygous for the
      5-HTTLPR short allele displayed a clear lateral shift of dorsolateral frontal
      activity to the right, which was virtually absent in participants carrying the
      long allele. The heightened electrocortical response to the aversive stimulation
      and its direction indicates a greater propensity of s/s homozygotes to experience
      withdrawal oriented affect in response to negative emotion cues in the
      environment. Moreover, together with previous research the findings support the
      notion of a link between the serotonergic system and self-regulation related to
      avoidance motivation, and a link between the dopaminergic system and self
      regulation related to approach motivation.

PMID- 24040882
TI  - A test of Spielberger's state-trait theory of anger with adolescents: five
      hypotheses.
AB  - Spielberger's state-trait theory of anger was investigated in adolescents (n =
      201, ages 10-18, 53% African American, 47% European American, 48% female) using
      Deffenbacher's five hypotheses formulated to test the theory in adults. Self
      reported experience, heart rate (HR), systolic blood pressure (SBP), and
      diastolic blood pressure (DBP) responses to anger provoking imagery scripts found
      strong support for the application of this theory to adolescents. Compared with
      the low trait anger (LTA) group, adolescents with high trait anger (HTA) produced
      increased HR, SBP, and DBP, and greater self-report of anger to anger imagery
      (intensity hypothesis) but not greater self-report or cardiovascular reactivity
      to fear or joy imagery (discrimination hypothesis). The HTA group also reported
      greater frequency and duration of anger episodes and had longer recovery of SBP
      response to anger (elicitation hypothesis). The HTA group was more likely to
      report negative health, social, and academic outcomes (consequence hypothesis).
      Adolescents with high hostility reported more maladaptive coping with anger, with
      higher anger-in and anger-out than adolescents with low hostility (negative
      expression hypothesis). The data on all five hypotheses supported the notion that
      trait anger is firmly entrenched by the period of adolescence, with few
      developmental differences noted from the adult literature.

PMID- 24040884
TI  - Memory for emotionally arousing items: context preexposure enhances subsequent
      context-item binding.
AB  - Emotionally arousing events are better remembered than neutral events. Not all
      components of these events, however, are equally well remembered and bound in
      memory. Although arousal enhances memory for central information, it tends to
      impair memory for peripheral details, referred to as central/peripheral trade
      off. Therefore, people often have difficulties remembering which emotional
      stimuli were encountered in which contexts. The present study asked whether such
      context-item binding could be enhanced when individuals are familiarized with
      context images that later serve as background cues for emotionally arousing
      stimuli. Familiarization allows for context encoding prior to the encounter of
      emotionally arousing stimuli. Thus, only few attentional or cognitive resources
      may be required for context encoding when the arousing stimuli are presented,
      which might then allow for more efficient context-item binding. In line with this
      hypothesis, we show that context-item binding significantly improved under these
      conditions for emotionally negative stimuli. Our results suggest that context
      familiarity promotes context-item binding for emotional events.

PMID- 24040885
TI  - Unique device operations by combining optical-memory effect and electrical-gate
      modulation in a photochromism-based dual-gate transistor.
AB  - We demonstrate a new device that combines a light-field effect and an electrical
      gate effect to control the drain current in a dual-gate transistor. We used two
      organic layers, photochromic spiropyran (SP)-doped poly(triarylamine) (PTAA) and
      pristine PTAA, as top and bottom channels, respectively, connected to common
      source and drain electrodes. The application of voltage to the top and bottom
      gates modulated the drain current through each layer independently. UV
      irradiation suppressed the drain current through the top channel. The suppressed
      current was then maintained even after the UV light was turned off because of an
      optical memory effect induced by photoisomerization of SP. In contrast, UV
      irradiation did not change the drain current in the bottom channel. Our dual-gate
      transistor thus has two organic channels with distinct photosensitivities: an
      optically active SP-PTAA film and an optically inactive PTAA film. This device
      configuration allows multi-level switching via top- and bottom-gate electrical
      fields with an optical-memory effect. 

PMID- 24040886
TI  - Lead binding to soil fulvic and humic acids: NICA-Donnan modeling and XAFS
      spectroscopy.
AB  - Binding of lead (Pb) to soil fulvic acid (JGFA), soil humic acids (JGHA, JLHA),
      and lignite-based humic acid (PAHA) was investigated through binding isotherms
      and XAFS. Pb binding to humic substances (HS) increased with increasing pH and
      decreasing ionic strength. The NICA-Donnan model described Pb binding to the HS
      satisfactorily. The comparison of the model parameters showed substantial
      differences in median Pb affinity constants among JGFA, PAHA, and the soil HAs.
      Milne's "generic" parameters did not provide an adequate prediction for the soil
      samples. The Pb binding prediction with generic parameters for the soil HAs was
      improved significantly by using the value n(Pb1) = 0.92 instead of the generic
      value n(Pb1) = 0.60. The n(Pb1)/n(H1) ratios obtained were relatively high,
      indicating monodentate Pb binding to the carboxylic-type groups. The nPb2/nH2
      ratios depended somewhat on the method of optimization, but the values were
      distinctly lower than the n(Pb1)/nH1 ratios, especially when the optimization was
      based on Pb bound vs log [Pb(2+)]. These low values indicate bidentate binding to
      the phenolic-type groups at high Pb concentration. The NICA-Donnan model does not
      consider bidentate binding of Pb to a carboxylic- and a phenolic-type group. The
      EXAFS results at high Pb loading testified that Pb was bound in bidentate
      complexes of one carboxylic and one phenolic group (salicylate-type) or two
      phenolic groups (catechol-type) in ortho position.

PMID- 24040887
TI  - The level of control of mild asthma in general practice: an observational
      community-based study.
AB  - OBJECTIVE: The aim of the present community-based study was to evaluate the level
      of asthma control in patients with mild asthma, regularly treated with inhaled
      steroids (ICS). METHOD: This observational cross-sectional study included
      patients registered in the general practitioner (GP) database and with at least
      three prescriptions of ICS in the last 12 months. Patients were asked to refer to
      the doctor's office for a standardised interview. The level of asthma control was
      self-measured by the patients using the Asthma Control Test (ACT)TM (Quality
      Metric, Inc.). RESULTS: The study included 950 asthmatic patients, referred by
      540 GPs: 54.5% were females, mean age was 51 (+/-19.1) years; 59.5% were non
      smokers, 22.5% were current smokers and 18.0% were former smokers; 81.1% of the
      patients were on ICS in the last 4 weeks. Only 38.6% of patients had a spirometry
      in the last 12 months. According to the ACT, 13.7% of the asthmatic patients were
      totally controlled, 51.0% well controlled, and 35.3% poorly controlled. Smoking
      habit, older age (>60) and living in Central or Southern Italy were associated
      with poorer control. In the last 12 months 4.5% of patients had an asthma-related
      hospitalisation, 5.3% an emergency visit and 18.9% a specialist visit.
      CONCLUSIONS: More than one of three patients had poor asthma control, despite
      being considered by their GPs as mild asthmatics and treated with ICS. Asthmatic
      patients need to be regularly re-evaluated. Treatment is often inadequate and
      should be targeted to improve control and reduce asthma morbidity (SAM104964).

PMID- 24040888
TI  - Peyronie's disease: epidemiology, diagnosis, and management.
AB  - OBJECTIVE: Peyronie's disease (PD) is a progressive fibrotic disorder of the
      penis that is characterized by formation of collagen plaques on the tunica
      albuginea of the penis that may result in penile deformity, pain (typically early
      in the disease course), and often occurs in conjunction with erectile
      dysfunction. This review's purpose is to raise awareness of PD among primary care
      physicians, who are likely to provide the initial diagnosis and information to
      patients. METHODS: PubMed was searched for articles related to epidemiology,
      diagnosis, and management of PD. Reference lists of relevant articles were also
      examined for further pertinent research. Following the goals of this review,
      references were selected based on their appropriateness for a primary care
      audience. RESULTS: The symptoms of PD may physically limit intercourse and impose
      a severe physical and psychological burden. The course of PD includes an early
      'inflammatory' phase that may last 1-18 months and a subsequent 'stable' phase.
      In the early phase, patients may experience penile pain as the tunical plaque
      develops. During the stable phase, the plaque becomes more organized, penile
      curvature stabilizes, and the pain usually subsides. Currently, there are no US
      Food and Drug Administration approved therapies that have shown significant
      efficacy for PD. Nonsurgical treatment options are often used to manage PD with
      variable success. Most studies of nonsurgical management of PD are small, poorly
      controlled, and include patients in variable disease stages. Surgical treatment
      of PD is reserved for stable patients with erectile dysfunction and penile
      deformity that impairs sexual function. CONCLUSION: PD is frequently undiagnosed.
      Even when PD is correctly identified, choice of treatment is problematic, based
      on the limited currently available clinical data demonstrating clinical benefits
      associated with treatment. Newer medications in clinical testing seem to offer
      some potential benefit for men with PD, though further research is necessary.

PMID- 24040889
TI  - Clinical course for patients with peritoneal carcinomatosis excluded from
      cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
AB  - BACKGROUND: Cytoreductive surgery combined with 'Hyperthermic IntraPEritoneal
      Chemotherapy' (HIPEC) represents the only potentially curative treatment
      available for carcinomatosis secondary to colorectal cancer (CRC), pseudomyxoma
      peritonei (PMP), malignant peritoneal mesothelioma (MM) and goblet cell carcinoma
      (GCC). Despite preoperative investigation some patients are excluded
      perioperatively because of unacceptably massive tumor extent. The data available
      on the clinical course of these patients are sparse. The aim of this study was to
      investigate mortality, morbidity and clinical course for patients who were
      excluded. METHODS: This was a retrospective observational study based on records
      from 35 patients (21 men, 14 women) treated in a national center (Surgical
      Department P, Aarhus University Hospital) from June 2006 to August 2011 and
      excluded from the cytoreductive surgery perioperatively. The study population
      included patients aged 18 to 70 years with CRC (n = 19), PMP (n = 11), MM (n = 3)
      or GCC (n = 2). Vital status was obtained by 29 November 2012. Three patients
      were lost to follow-up. RESULTS: The 30-day mortality rate was 0%. Postoperative
      complications within 30 days occurred in three patients (9.4%). In all, 19
      patients (54%) had palliative surgery during exploratory laparotomy. In total, 28
      patients (88%) received postoperative palliative chemotherapy. The median
      survival for CRC and PMP patients was 12.7 (95% CI 4.0 to 21.4) and 26.9 (95% CI
      25.7 to 28.1) months, respectively. CONCLUSIONS: Exploratory laparotomy for
      intended curative treatment of peritoneal carcinomatosis did not imply major
      morbidity or mortality for patients excluded from treatment due to advanced stage
      of disease.

PMID- 24040890
TI  - Organocatalyzed asymmetric synthesis of dihydrodibenzofurans based on a dienamine
      process.
AB  - The first organocatalyzed asymmetric method for the synthesis of
      dihydrodibenzofurans based on a dienamine process has been developed. This two
      step protocol works with a broad range of substrates and delivers only the cis
      diastereomer in good yield with up to 91% ee. The enantioenriched products have
      been transformed to highly functionalized and partially hydrogenated
      dibenzofurans in excellent diastereoselectivities. 

PMID- 24040891
TI  - Comparison of flavonoids, phenolic acids, and antioxidant activity of explosion
      puffed and sun-dried jujubes (Ziziphus jujuba Mill.).
AB  - The goal of the present study was to investigate the effect of explosion puffing
      and sun-drying on individual phenolic acids in four forms (free, esters,
      glycosides, and insoluble-bound), flavonoids, total phenolic content (TPC), and
      their antioxidant activity on jujube samples. Phenolic compounds were identified
      and quantified using high-performance liquid chromatography. Antioxidant capacity
      of jujube samples was evaluated by 2,2-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid) radical scavenging activity and total reducing power. The results
      showed that all samples significantly differed in their phenolic contents,
      phenolic acid and flavonoid composition, and antioxidant activities. The
      explosion-puffed jujubes had the highest total gallic, p-hydroxybenzoic,
      vanillic, p-coumaric, ferulic acids, and rutin contents. Also, explosion-puffed
      jujubes contained a higher level of total phenolics and antioxidant activity than
      their counterparts. Among phenolic acid fractions in four forms, each form of
      phenolic acids in explosion-puffed jujubes had the most abundant content,
      followed by fresh and sun-dried jujubes. The glycosided and insoluble-bound
      phenolic acid fractions for each sample represented the highest TPC and the
      strongest antioxidant activity. The results indicated explosion puffing was a
      good choice for jujube processing.

PMID- 24040893
TI  - Space-efficient and exact de Bruijn graph representation based on a Bloom filter.
AB  - BACKGROUND: The de Bruijn graph data structure is widely used in next-generation
      sequencing (NGS). Many programs, e.g. de novo assemblers, rely on in-memory
      representation of this graph. However, current techniques for representing the de
      Bruijn graph of a human genome require a large amount of memory (>=30 GB).
      RESULTS: We propose a new encoding of the de Bruijn graph, which occupies an
      order of magnitude less space than current representations. The encoding is based
      on a Bloom filter, with an additional structure to remove critical false
      positives. CONCLUSIONS: An assembly software implementing this structure, Minia,
      performed a complete de novo assembly of human genome short reads using 5.7 GB of
      memory in 23 hours.

PMID- 24040892
TI  - Pulmonary function, chronic respiratory symptoms, and health-related quality of
      life among adults in the United States--National Health and Nutrition Examination
      Survey 2007-2010.
AB  - BACKGROUND: We examined the association of impaired lung function and respiratory
      symptoms with measures of health status and health-related quality of life
      (HRQOL) among US adults. METHODS: The sample included 5139 participants aged 40
      79 years in the National Health and Nutrition Examination Survey 2007-2010 who
      underwent spirometric testing and responded to questions about respiratory
      symptoms, health status, and number of physically unhealthy, mentally unhealthy,
      or activity limitation days in the prior 30 days. RESULTS: Among these adults,
      7.2% had restrictive impairment (FEV1/FVC >= 70%; FVC < 80% of predicted), 10.9%
      had mild obstruction (FEV1/FVC < 70%; FEV1 >= 80% predicted), and 9.0% had
      moderate-severe obstruction (FEV1/FVC < 70%; FEV1 < 80% predicted). Individuals
      with restrictive impairment or moderate-severe obstruction were more likely to
      report fair/poor health compared to those with normal lung function (prevalence
      ratio (PR) =1.5 [95% CI: 1.2-1.9] and 1.5 [1.3-1.8]), after controlling for
      sociodemographics, non-respiratory chronic diseases, body mass index, smoking,
      and respiratory symptoms. Frequent mental distress (FMD; >=14 mentally unhealthy
      days), frequent physical distress (FPD; >=14 physically unhealthy days), and
      frequent activity limitation (FAL; >=14 activity limitation days) did not differ
      by lung function status. Adults who reported any respiratory symptoms (frequent
      cough, frequent phlegm, or past year wheeze) were more likely to report fair/poor
      health (PR = 1.5 [1.3-1.7]), FPD (PR = 1.6 [1.4-1.9]), FMD (PR = 1.8 [1.4-2.2]),
      and FAL (PR = 1.4 [1.1-1.9]) than those with no symptoms. CONCLUSIONS: These
      results suggest the importance of chronic respiratory symptoms as potential risk
      factors for poor HRQOL and suggest improved symptom treatment and prevention
      efforts would likely improve HRQOL.

PMID- 24040894
TI  - Impulsivity, cognitive function, and their relationship in heroin-dependent
      individuals.
AB  - There is mixed evidence concerning cognitive function and heroin dependence. In
      this study, abstinent heroin-dependent individuals (n = 86) and age- and sex
      matched non-drug-using controls (n = 88) were compared on self-report measures of
      impulsivity and computerized assessments of cognitive function. Abstinent heroin
      dependent individuals reported greater motor impulsivity and experience seeking
      and showed functional weaknesses in cognitive ability, including impulsivity and
      distractibility (d = 0.28 to 0.49), but not decision making or working memory.
      Self-reported impulsivity was uncorrelated with cognitive function. These results
      suggest underlying brain-related factors in heroin dependence and have
      implications for therapeutic intervention. 

PMID- 24040895
TI  - Exposing bovine cumulus-oocyte complexes to aromatizable androgen restore serum
      induced low estradiol production in vitro.
AB  - We aimed in this study to assess whether serum-decreased bovine cumulus-oocyte
      complex (COC) steroidogenesis during in vitro maturation (IVM) is caused by
      deficient androgen milieu. For this approach, bovine COCs were cultured in serum
      supplemented IVM medium in the presence or absence of 1 MUM androstenedione.
      After 24 h of culture, medium was collected and analyzed for its content of
      estradiol-17beta (E2) and progesterone (P4). Medium E2 content markedly increased
      after incubation of COCs with androstenedione (17.52 +/- 1.86 ng/ml to the
      androgen group; 0.32 +/- 0.05 ng/ml to the non-androgen group). No significant
      difference in the P4 content was detected despite the presence of androstenedione
      (21.83 +/- 1.61 ng/ml to the androgen group; 21.73 +/- 1.67 ng/ml to the non
      androgen group). Our data provide compelling evidence that bovine COCs
      steroidogenesis remains functional during culture in serum-supplemented medium
      and suggest that serum-induced decreased COCs estradiol secretion is caused by
      deficiency of an aromatizable androgen source.

PMID- 24040896
TI  - High-risk patients with differentiated thyroid cancer T4 primary tumors achieve
      remnant ablation equally well using rhTSH or thyroid hormone withdrawal.
AB  - BACKGROUND: Few data exist on using thyrotropin alfa (recombinant human thyroid
      stimulating hormone [rhTSH]) with radioiodine for thyroid remnant ablation of
      patients who have T4 primary tumors (invasion beyond the thyroid capsule).
      METHODS: A retrospective chart review protocol at nine centers in Europe was set
      up with special waiver of need for informed consent, along with a careful
      procedure to avoid selection bias when enrolling patients into the database. Data
      on 144 eligible patients with T4 tumors were collected (T4, N0-1, M0-1; mean age
      49.7 years; 65% female; 88% papillary cancer). All had received (131)I remnant
      ablation following TSH stimulation with rhTSH or thyroid hormone withdrawal (THW)
      since January 2000 (rhTSH n=74, THW n=70). The primary endpoint was based on
      evaluation of diagnostic radioiodine scan thyroid bed uptake more than six months
      after the ablation procedure, while stimulated serum Tg was a secondary endpoint.
      Safety was evaluated within 30 days after rhTSH or (131)I. RESULTS: Successful
      ablation judged by scan was achieved in 65/70 (92.9%) of rhTSH and in 61/67
      (91.0%) of THW patients; the success rates were comparable, since noninferiority
      criteria were met. Although some patients in the initial cohort had tumor in
      cervical nodes and metastases, considering all evaluable patients regardless of
      various serum anti-Tg antibody assessments, the stimulated Tg was <2 ng/mL in
      48/70 (68.6%) and 39/67 (58.2%) in rhTSH and THW groups respectively; if patients
      with anti-Tg antibody levels >30 IU/mL were excluded, the stimulated Tg was <2
      ng/mL in 42/62 (67.7%) and 37/64 (57.8%) respectively. No serious adverse events
      occurred within the 30-day window after ablation. CONCLUSIONS: Use of rhTSH as
      preparation for thyroid remnant ablation in patients with T4 primary tumors
      achieved a rate of ablation success that was high and noninferior to the rate
      seen after THW, and rhTSH was well tolerated.

PMID- 24040897
TI  - The lipid peroxidation end-product and oxidant 4-hydroxynonenal induces insulin
      resistance in rat slow-twitch skeletal muscle.
AB  - CONTEXT: The lipid peroxidation end-product and oxidant 4-hydroxynonenal (4-HNE)
      impairs cell function. However, the impact of 4-HNE on the glucose transport
      system in mammalian slow-twitch skeletal muscle is not known. OBJECTIVE: We
      assessed the effects of 4-HNE on insulin signalling and glucose transport
      activity in slow-twitch muscle by incubating soleus strips from lean Zucker rats
      with 4-HNE (50 uM) in the absence or presence of insulin (5 mU/ml) for up to 6
      hr. RESULTS: Insulin-stimulated glucose transport activity was significantly
      (p<0.05) decreased by 4-HNE at 2 hr. AS160 Thr(642) phosphorylation was decreased
      at 2 hr, whereas Akt Ser473 phosphorylation and IRS-1 protein expression were not
      substantially changed until 4 hr. IRS-2 protein expression was slightly decreased
      only at 6 hr. CONCLUSIONS: The lipid peroxidation end-product and oxidant 4-HNE
      induces insulin resistance of glucose transport activity in rat slow-twitch
      skeletal muscle, initially associated with impaired phosphorylation of AS160.

PMID- 24040898
TI  - Management of acute asthma in the emergency department.
AB  - Asthma is primarily a clinical diagnosis that is made from a combination of
      historical features and clinical examination findings. The mainstay of asthma
      treatment includes short-acting beta agonist therapy (albuterol) and steroids.
      Handheld inhalers are sufficient for most inhaled therapy; all patients on
      inhalers should be provided with a spacer. The severity of asthma exacerbations
      is determined by 3 features: (1) clinical presentation, (2) peak expiratory flow
      rates, and (3) vital signs. Additional testing, such as chest x-ray and blood gas
      measurements, is reserved for select patients. Spirometry aids in the diagnosis
      of asthma and measurement of severity, but it is not always required, nor should
      it be solely relied upon to make disposition decisions. Inhaled ipratropium
      decreases hospitalization rates, and it should be routinely used. Levalbuterol
      provides little to no advantage over less-expensive racemic albuterol.
      Noninvasive positive pressure ventilation may be utilized in patients with
      moderate to severe exacerbations. Ketamine may be considered in severe
      exacerbations, but it should not be used routinely. Magnesium sulfate may be
      beneficial in severe asthma exacerbations, but routine use for mild to moderate
      exacerbations is not indicated. 

PMID- 24040899
TI  - The predictive value of mental health for long-term sickness absence: the Major
      Depression Inventory (MDI) and the Mental Health Inventory (MHI-5) compared.
AB  - BACKGROUND: Questionnaires are valuable for population surveys of mental health.
      Different survey instruments may however give different results. The present
      study compares two mental health instruments, the Major Depression Inventory
      (MDI) and the Mental Health Inventory (MHI-5), in regard to their prediction of
      long-term sickness absence. METHOD: Questionnaire data was collected from N =
      4153 Danish employees. The questionnaire included the MDI and the MHI-5. The
      information of long-term sickness absence was obtained from a register. We used
      Cox regression to calculate covariance adjusted hazard ratios for long-term
      sickness absence for both measures. RESULTS: Both the MDI and the MHI-5 had a
      highly significant prediction of long-term sickness absence. A one standard
      deviation change in score was associated with an increased risk of long-term
      sickness absence of 27% for the MDI and 37% for the MHI-5. When both measures
      were included in the same analysis, the MHI-5 performed best. CONCLUSION: In
      general population surveys, the MHI-5 is a better predictor of long-term sickness
      absence than the MDI.

PMID- 24040900
TI  - Analysis of the structural integrity of SU-8-based optofluidic systems for small
      molecule crystallization studies.
AB  - The use of SU-8-based optofluidic systems (OFS) is validated as an affordable and
      easy alternative to expensive glass device manufacturing for small-molecule
      crystallization studies and, in comparison with other polymers, able to withstand
      most organic solvents. A comparison between two identical OFS (using SU-8 and
      poly(dimethylsiloxane), PDMS) against the 36 most commonly used organic solvents
      for small-molecule crystallization studies have confirmed both the structural and
      optical stability of the SU-8, whereas PDMS suffered from unsealing or tearing in
      most cases. In order to test its compatibility, measurements before and after 24
      h of continued exposure against solvents have been pursued. Here, three aspects
      have been considered: in the macroscale, swelling has been determined by
      analyzing the variations in the optical path in the OFS. For determining
      compatibility at microscale, fabricated SU-8 micropatterns were solvent-etched
      and subsequently characterized by scanning electron microscopy (SEM). Roughness
      of the polymer has also been studied through atomic force microscopy (AFM)
      measurements at the nanoscale. Experimental measurements of PDMS swelling were in
      accordance with previously reported observations, while SU-8 displayed a great
      stability against all the tested solvents. Through this experimental procedure we
      also show that the OFS are suitable for real-time, on-chip, UV-vis spectroscopy.
      Micro- and nanoscale observations did not show apparent corrosion on SU-8
      surface. Also, two commonly used carrier fluids for microdroplet generation (FC
      70 Fluorinert oil and silicone oil) were also tested against the different
      solvents with the aim of providing useful information for later microbatch
      experiments. 

PMID- 24040902
TI  - Spouses' involvement in their partners' diabetes management: associations with
      spouse stress and perceived marital quality.
AB  - Spouses frequently attempt to influence (control) or support their chronically
      ill partners' adherence behaviors. Studies have documented effects of spousal
      control and support on chronically ill individuals, but little is known about how
      these two forms of involvement in a partner's disease management may be
      associated with spouses' stress or the quality of their interactions with their
      ill partners. The current study sought to address this gap by examining spouses'
      day-to-day involvement in their marital partner's management of type 2 diabetes
      (n = 129). Multilevel analyses of daily diary data revealed that on days when
      spouses exerted control, they reported more stress and more tense marital
      interactions, although these associations were more pronounced when patients
      exhibited poor adherence, had been ill for a longer period of time, and had more
      comorbid health conditions. On days when spouses provided support, in contrast,
      they reported less stress and more enjoyable marital interactions. The findings
      from the current study suggest that spouses' day-to-day stress and quality of
      interactions with their partners are associated with spouses' involvement in
      their partners' disease management, with health-related social control and
      support exhibiting distinctive associations.

PMID- 24040901
TI  - Exploring the impact of skin tone on family dynamics and race-related outcomes.
AB  - Racism has historically been a primary source of discrimination against African
      Americans, but there has been little research on the role that skin tone plays in
      explaining experiences with racism. Similarly, colorism within African American
      families and the ways in which skin tone influences family processes is an
      understudied area of research. Using data from a longitudinal sample of African
      American families (n = 767), we assessed whether skin tone impacted experiences
      with discrimination or was related to differences in quality of parenting and
      racial socialization within families. Findings indicated no link between skin
      tone and racial discrimination, which suggests that lightness or darkness of skin
      does not either protect African Americans from or exacerbate the experiences of
      discrimination. On the other hand, families displayed preferential treatment
      toward offspring based on skin tone, and these differences varied by gender of
      child. Specifically, darker skin sons received higher quality parenting and more
      racial socialization promoting mistrust compared to their counterparts with
      lighter skin. Lighter skin daughters received higher quality parenting compared
      with those with darker skin. In addition, gender of child moderated the
      association between primary caregiver skin tone and racial socialization
      promoting mistrust. These results suggest that colorism remains a salient issue
      within African American families. Implications for future research, prevention,
      and intervention are discussed.

PMID- 24040903
TI  - Longitudinal patterns of relationship adjustment among German parents.
AB  - Although there have been many studies that have examined the trajectory of
      relationship adjustment among newlywed couples in the United States, less is
      known about the trajectory of relationship adjustment in other countries and over
      other developmental periods of relationships, such as among families with young
      children. In this study, we used latent growth curve mixture modeling to examine
      the trajectories of relationship adjustment among German parents across a 4-year
      period (N = 242). Approximately 90% of men and women could be classified as
      showing high relationship adjustment and a stable or increasing trajectory. The
      remaining 10%, were initially more distressed and showed a decline in
      relationship adjustment over time. In addition, latent relationship adjustment
      trajectory class significantly predicted change in men's depressive symptoms over
      the 4 years; for women, relationship-adjustment trajectory class was related to
      depressive symptom levels, but did not predict change over time.

PMID- 24040904
TI  - Poly(dimethylsiloxane) oil absorbent with a three-dimensionally interconnected
      porous structure and swellable skeleton.
AB  - Cleanup of oil spills is a worldwide challenge to prevent serious environmental
      pollution. A new kind of poly(dimethylsiloxane) (PDMS) oil absorbent with high
      absorption capacity and excellent reusability was prepared and used for oil/water
      separation. The preparation process of PDMS oil absorbents involves direct curing
      of a PDMS prepolymer in a p-xylene solution in the presence of commercial sugar
      particles, which is simple and economic. PDMS oil absorbents have interconnected
      pores and a swellable skeleton, combining the advantages of porous materials and
      gels. Absorption capacities of PDMS oil absorbents are 4-34 g/g for various oils
      and organic solvents, which are 3 times that reported previously. Owing to their
      hydrophobicity and oleophilicity, the as-obtained PDMS oil absorbents can
      selectively collect oils or organic solvents from water. The absorption process
      can be finished within tens of seconds. Furthermore, the absorbed oils or organic
      solvents can be recovered by compressing the oil absorbents, and after 20
      absorbing/recovering cycles, PDMS oil absorbents show little loss of their
      absorption capacities and own weights. 

PMID- 24040905
TI  - Mechanistic investigation of mercury sorption by Brazilian pepper biochars of
      different pyrolytic temperatures based on X-ray photoelectron spectroscopy and
      flow calorimetry.
AB  - We investigated the mechanisms of Hg sorption onto biochars produced from
      Brazilian pepper (BP; Schinus terebinthifolius) at 300, 450, and 600  degrees C
      using different analytical techniques. The Hg sorption capacity of BP300, BP450,
      and BP600 was 24.2, 18.8, and 15.1 mg g(-1) based on Langmuir isotherm. FTIR data
      suggested the participation of phenolic hydroxyl and carboxylic groups in Hg
      sorption by biochars. XPS analysis showed that 23-31% and 77-69% of sorbed Hg was
      associated with carboxylic and phenolic hydroxyl groups in biochars BP300-450,
      whereas 91% of sorbed Hg was associated with a graphite-like domain on an
      aromatic structure in BP600 biochar, which were consistent with flow calorimetry
      data. Based on flow calorimetry, sorption of K and Ca onto biochar was
      exchangeable with the molar heat of sorption of 3.1 kJ mol(-1). By comparison, Hg
      sorption was via complexation with functional groups as it was not exchangeable
      by K or Ca with molar heat of sorption of -19.7, -18.3, and -25.4 kJ mol(-1) for
      BP300, BP450, and BP600. Our research suggested that Hg was irreversibly sorbed
      via complexation with phenolic hydroxyl and carboxylic groups in low temperature
      biochars (BP300 and BP450) and graphite-like structure in high temperature
      biochar (BP600). 

PMID- 24040906
TI  - A review of barriers to effective asthma management in Puerto Ricans: cultural,
      healthcare system and pharmacogenomic issues.
AB  - BACKGROUND: Among the Hispanic community, Puerto Ricans have the highest
      prevalence of asthma and manifest the worst outcomes. The expected growth of the
      Hispanic population in the USA in the next several decades make elimination of
      disparate care in Puerto Rican asthmatics a matter of national importance. The
      purpose of this review of the literature (ROL) is to examine a variety of health
      system, genetic and cultural barriers in the Puerto Rican community which have
      created disparities in asthma care and outcomes among adult and pediatric
      Hispanic populations. In addition, this ROL describes several culturally
      sensitive, community-based educational interventions which can be used as a
      framework for future projects to improved asthma outcomes. METHODS: Databases
      searched included Medline, PubMED, EBSCOhost, PsycINFO, CINAHL, Google Scholar
      and ERIC. Papers published in English from January 1990 to January 2012 were
      reviewed. RESULTS: Health system policies, insurer compensation patterns,
      clinician attitudes and cultural values/folk remedies in the Puerto Rican
      community represent barriers to effective asthma management, the use of
      controller medication and the implementation of educational interventions. In
      addition, genetic factors involving the beta-2 adrenergic receptor gene, which
      impair the response to albuterol, appear to contribute to poorer outcomes in
      Puerto Rican asthmatics. In contrast, several comprehensive, community-based,
      culturally sensitive educational interventions such as Controlling Asthma in
      American Cities Project (CAACP), the Racial and Ethnic Approach to Community
      Health in the US Program and Healthy Hoops programs (REACH) have been described.
      CONCLUSIONS: We believe that culturally sensitive community-based asthma
      education programs can serve as models for programs targeted toward Puerto Ricans
      to help decrease asthma morbidity. Moreover, greater sensitivity to Puerto Rican
      mores and folk remedies on the part of healthcare providers may improve the
      patient-clinician rapport and, hence, asthma outcomes. Finally, given ethnically
      based differences in pharmacogenomics, clinical trials targeting the Puerto Rican
      population may help to better define optimal asthma medication regimens in this
      ethnic group.

PMID- 24040907
TI  - Biomarkers in COPD: is mortality the Holy Grail?

PMID- 24040908
TI  - The COPD pipeline XXIV.

PMID- 24040909
TI  - Monodispersed brush-like conjugated polyelectrolyte nanoparticles with efficient
      and visualized siRNA delivery for gene silencing.
AB  - RNA interference is supposed to be one of the most powerful technologies for
      suppression of genes and treatment of diverse human diseases while the safe
      delivery and visualization of siRNA were still challenging. In this text, a novel
      type of monodispersed conjugated polymer nanoparticles PFNBr with brush-like
      molecular structure was introduced into siRNA delivery system. The nanoparticles
      exhibited dual functions conveniently in the delivery system which can not only
      carry high amount of siRNA to penetrate intracellularly for knocking down
      targeted mRNA but also act as signal agents for siRNA tracking and cellular
      imaging. Due to the high density side chains with positive charges and more
      extended conformation of the spatial structure, PFNBr nanoparticles as
      nanocarrier for siRNA provided outstanding capture ability (1 mol polymer to more
      than 32.5 mol siRNA) and enhanced protection capability of siRNA molecules from
      degradation. Here, it should be noted that the concentration of carrier in the
      working platform was lowered from the level of MUmol/L to nmol/L compared with
      other conjugated polymer delivery systems due to the outstanding carrying
      capacity of PFNBr. And meanwhile, this system acquired high gene silence
      efficiency and good biocompatibility. The proposed complex nanoparticles
      efficiently transfected siPlk1 into PANC-1 cells and induced high knockdown
      efficiency for targeted Plk1 mRNA to 23.9% and no significant cytotoxicity of the
      PFNBr/siRNA complexes was shown. Therefore, this working platform provides a
      solution to most of the common problems associated with the siRNA delivery,
      visualization, and therapeutic applications, and keeps a bright outlook for the
      development of new nucleic acid-based therapeutics and simultaneously for
      fluorescent bioimaging. 

PMID- 24040910
TI  - Lentiviral-mediated RNA interference targeting stathmin1 gene in human gastric
      cancer cells inhibits proliferation in vitro and tumor growth in vivo.
AB  - BACKGROUND: Gastric cancer is highly aggressive disease. Despite advances in
      diagnosis and therapy, the prognosis is still poor. Various genetic and molecular
      alterations are found in gastric cancer that underlies the malignant
      transformation of gastric mucosa during the multistep process of gastric cancer
      pathogenesis. The detailed mechanism of the gastric cancer development remains
      uncertain. In present study we investigated the potential role of stathmin1 gene
      in gastric cancer tumorigenesis and examined the usefulness of RNA interference
      (RNAi) targeting stathmin1 as a form of gastric cancer treatment. METHODS: A
      lentiviral vector encoding a short hairpin RNA (shRNA) targeted against stathmin1
      was constructed and transfected into the packaging cells HEK 293 T and the viral
      supernatant was collected to transfect MKN-45 cells. The transwell chemotaxis
      assay and the CCK-8 assay were used to measure migration and proliferation of
      tumor cells, respectively. Quantitative real-time PCR and western blotting were
      used to detect the expression levels of stathmin1. RESULTS: Lentivirus mediated
      RNAi effectively reduced stathmin1 expression in gastric cells. Significant
      decreases in stathmin1 mRNA and protein expression were detected in gastric cells
      carrying lentiviral stathmin-shRNA vector and also significantly inhibited the
      proliferation, migration in gastric cancer cells and tumorigenicity in Xenograft
      Animal Models. CONCLUSIONS: Our findings suggest that stathmin1 overexpression is
      common in gastric cancer and may play a role in its pathogenesis. Lentivirus
      mediated RNAi effectively reduced stathmin1 expression in gastric cells. In
      summary, shRNA targeting of stathmin1 can effectively inhibits human gastric
      cancer cell growth in vivo and may be a potential therapeutic strategy for
      gastric cancer.

PMID- 24040911
TI  - Metabolic syndrome and carotid intima-media thickness in chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: The aim of this study is to investigate the prevalence of metabolic
      syndrome (MetS), carotid intima media thickness (IMT), and serum C-reactive
      protein (CRP) levels in patients with chronic obstructive pulmonary disease
      (COPD), and the possible relationships among them. METHODS: Fifty stable COPD
      patients and 40 healthy controls were included in the study. The participants
      were further divided into four groups according to their smoking status.
      Pulmonary function tests were performed in COPD patients. Anthropometric
      measurements and blood chemistry analysis, serum CRP levels and carotid intima
      media thickness (IMT) measurements were performed in all the study population.
      RESULTS: Prevalence of metabolic syndrome was 43% in COPD patients and 30% in the
      control group (p = 0.173). FEV1% and FEV1/FVC were higher in COPD patients with
      MetS (p = 0.001 and p = 0.014, respectively) compared to those without MetS.
      Prevalence of MetS was significantly different among the COPD patients with
      different stages (p = 0.017) with the highest value in stage 2 (59%). Carotid IMT
      was significantly higher in COPD patients than in control group (1.07 +/- 0.25 mm
      and 0.86 +/- 0.18 mm, respectively; p < 0.001). Serum CRP levels were not
      different in COPD patients and controls, however they were higher in individuals
      with MetS compared to those without MetS regardless of COPD presence (p = 0.02).
      CONCLUSIONS: Early markers of atherogenesis, in terms of carotid IMT, were found
      to be higher in COPD patients than in healthy controls. MetS prevalence was
      observed to decrease as the severity of airflow obstruction increased. Therefore,
      screening COPD patients for these cardiovascular risk factors would be a novel
      approach even in absence of symptoms.

PMID- 24040912
TI  - A concise synthesis of (+)-salvadione B.
AB  - The novel hexacyclic triterpene salvadione B was synthesized in seven steps from
      the chiral quinone shown. The insight gained from this synthesis permitted a two
      step, one-pot sequence to introduce the three additional rings and seven chiral
      centers. 

PMID- 24040913
TI  - Atraumatic Flexor tendon retrieval- a simple method.
AB  - BACKGROUND: Zone 2 flexor tendon injuries still represent a challenging problem
      to hand surgeons despite the well developed surgical techniques and suture
      materials. Meticulous surgical repair with atraumatic handling of the severed
      tendon stumps and minimal damage to the tendon sheath are particularly important
      to prevent postoperative adhesions and ruptures in this area.In zone 2 flexor
      tendon injuries proximal to the vinculas, the cut ends of the flexor tendons
      retract to the palm with muscle contraction. To retrieve the severed proximal
      flexor tendon under tendon sheath and pulley system is very difficult without
      damaging these structures. Many techniques are described in the literature for
      the delivery of the retracted proximal tendon stump to the repair site. METHODS:
      In this report we would like to present a simple and relatively atraumatic
      technique that facilitates passing of the retracted flexor tendon through the
      pulleys in zone 2. We sutured the proximal tendon stump at the distal palmar
      crease with 3-0 polypropylene suture and used a 14 gauge plastic feeding tube,
      acting like a conduit for the passage of straightened needle to the finger.
      RESULTS: We have used this technique 21 times without any complication in our
      clinic. We have not seen any suture breakage during the passage or needle
      breakage due to the bending of the needle. CONCLUSIONS: We have found this
      technique is very simple and very effective in retrieving the retracted tendon
      stump without causing undue damage to the tendon stump or tendon sheath.

PMID- 24040914
TI  - Register-based data of psychosocial working conditions and occupational groups as
      predictors of disability pension due to musculoskeletal diagnoses: a prospective
      cohort study of 24,543 Swedish twins.
AB  - BACKGROUND: Occupations and psychosocial working conditions have rarely been
      investigated as predictors of disability pension in population-based samples.
      This study investigated how occupational groups and psychosocial working
      conditions are associated with future disability pension due to musculoskeletal
      diagnoses, accounting for familial factors in the associations. METHODS: A sample
      of 24,543 same-sex Swedish twin individuals was followed from 1993 to 2008 using
      nationwide registries. Baseline data on occupations were categorized into eight
      sector-defined occupational groups. These were further used to reflect
      psychosocial working conditions by applying the job strain scores of a Job
      Exposure Matrix. Cox proportional hazard ratios (HR) were estimated. RESULTS:
      During the 12-year (average) follow-up, 7% of the sample was granted disability
      pension due to musculoskeletal diagnoses. Workers in health care and social work;
      agriculture, forestry and fishing; transportation; production and mining; and the
      service and military work sectors were two to three times more likely to receive
      a disability pension than those in the administration and management sector. Each
      single unit decrease in job demands and each single unit increase in job control
      and social support significantly predicted disability pension. Individuals with
      high work strain or an active job had a lower hazard ratio of disability pension,
      whereas a passive job predicted a significantly higher hazard ratio. Accounting
      for familial confounding did not alter these results. CONCLUSION: Occupational
      groups and psychosocial working conditions seem to be independent of familial
      confounding, and hence represent risk factors for disability pension due to
      musculoskeletal diagnoses. This means that preventive measures in these sector
      defined occupational groups and specific psychosocial working conditions might
      prevent disability pension due to musculoskeletal diagnoses.

PMID- 24040915
TI  - Effect of melatonin treatment on developmental potential of somatic cell nuclear
      transferred mouse oocytes in vitro.
AB  - The beneficial effect of supplementing culture medium with melatonin has been
      reported during in vitro embryo development of species such as mouse, bovine and
      porcine. However, the effect of melatonin on mouse somatic cell nuclear transfer
      remains unknown. In this study, we assessed the effects of various concentrations
      of melatonin (10-6 to 10-12 M) on the in vitro development of mouse somatic cell
      nuclear transfer embryos for 96 h. Embryos cultured without melatonin were used
      as control. There was no significant difference in cleavage rates between the
      groups supplemented with melatonin, dimethyl sulphoxide (DMSO) and the control.
      The rate of development to blastocyst stage was significantly higher in the group
      supplemented with 10-12 M melatonin compared with the control group (P < 0.05).
      Thus, our data demonstrated that adding melatonin to pre-implantation mouse
      nuclear-transferred embryos can accelerate blastocyst formation.

PMID- 24040916
TI  - Solid colloids with surface-mobile DNA linkers.
AB  - Surface functionalization with bioinspired binding groups is increasingly used to
      steer nano- and microscale self-assembly processes, with complementary DNA
      "sticky ends" as one of the most notable examples. The fabrication of well
      organized structures is complicated, however, by the sharp
      association/dissociation transitions and the slow rearrangement kinetics
      intrinsic to collections of discrete, surface-immobilized binding groups and is
      aggravated by natural nonuniformities in the surface coating. Here, we
      demonstrate a novel system of solid microparticles functionalized with specific
      binding groups-in this case DNA linkers-that are fully mobile along the particle
      surface. These colloids display qualitatively new behavior and circumvent many of
      the commonly encountered issues. Importantly, the association/dissociation
      transition, and thereby the temperature window for equilibrium self-assembly, is
      much broader. We further find that the linkers are uniformly distributed above
      the DNA melting temperature, while visibly accumulating at the interparticle
      contacts below this temperature. The unique combination of binding group mobility
      with nondeformability, monodispersity, and facile manipulation of solid particles
      should have a profound impact on DNA-mediated and other bioinspired self-assembly
      approaches. Moreover, our highly tunable experimental system enables detailed
      model investigations that will also deepen our fundamental understanding of other
      systems with surface-mobile binding groups, for instance, biological ligand
      receptor interactions. 

PMID- 24040919
TI  - High-speed tandem mass spectrometric in situ imaging by nanospray desorption
      electrospray ionization mass spectrometry.
AB  - Nanospray desorption electrospray ionization (nano-DESI) combined with tandem
      mass spectrometry (MS/MS), high-resolution mass analysis of the fragment ions
      (m/Deltam = 17 500 at m/z 200), and rapid spectral acquisition enabled
      simultaneous imaging and identification of a large number of metabolites and
      lipids from 92 selected m/z windows (+/-1 Da) with a spatial resolution of better
      than 150 MUm. Mouse uterine sections of implantation sites on day 6 of pregnancy
      were analyzed in the ambient environment without any sample pretreatment. MS/MS
      imaging was performed by scanning the sample under the nano-DESI probe at 10
      MUm/s, while higher-energy collision-induced dissociation (HCD) spectra were
      acquired for a targeted inclusion list of 92 m/z values at a rate of ~6.3
      spectra/s. Molecular ions and their corresponding fragments, separated by high
      resolution mass analysis, were assigned on the basis of accurate mass
      measurement. Using this approach, we were able to identify and image both
      abundant and low-abundance isobaric and isomeric species within each m/z window.
      MS/MS analysis enabled efficient separation and identification of isomeric and
      isobaric phospholipids that are difficult to separate in full-scan mode.
      Furthermore, we identified several metabolites associated with early pregnancy
      and obtained the first 2D images of these molecules. 

PMID- 24040920
TI  - Risk of cardiovascular disease? A qualitative study of risk interpretation among
      patients with high cholesterol.
AB  - BACKGROUND: Previous studies have shown the importance of paying attention to lay
      peoples' interpretations of risk of disease, in order to explain health-related
      behavior. However, risk interpretations interplay with social context in complex
      ways. The objective was to explore how asymptomatic patients with high
      cholesterol interpret risk of cardiovascular disease. METHODS: Fourteen patients
      with high cholesterol and risk of cardiovascular disease were interviewed, and
      patterns across patient accounts were identified and analysed from an
      ethnographic approach. RESULTS: Information from the general practitioner about
      high cholesterol and risk of cardiovascular disease was reinterpreted in everyday
      social life. The risk associated with fatty foods was weighed against the
      pleasures of social and cultural events in which this type of food was common and
      cherished.A positive mindset was applied as a strategy to lower the risk of
      having high cholesterol, but knowledge about risk was viewed as a cause of
      anxiety and self-absorption, and this anxiety made the body susceptible to
      disease, hampering the chances for healthy life. CONCLUSION: Interpretations of
      high cholesterol and risk of cardiovascular disease are embedded in social
      relations and everyday life concerns. This should be addressed in general
      practice in preference-sensitive cases about risk-reducing medication. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT01187056.

PMID- 24040918
TI  - Oxidative modulation of voltage-gated potassium channels.
AB  - SIGNIFICANCE: Voltage-gated K+ channels are a large family of K+-selective ion
      channel protein complexes that open on membrane depolarization. These K+ channels
      are expressed in diverse tissues and their function is vital for numerous
      physiological processes, in particular of neurons and muscle cells. Potentially
      reversible oxidative regulation of voltage-gated K+ channels by reactive species
      such as reactive oxygen species (ROS) represents a contributing mechanism of
      normal cellular plasticity and may play important roles in diverse pathologies
      including neurodegenerative diseases. RECENT ADVANCES: Studies using various
      protocols of oxidative modification, site-directed mutagenesis, and structural
      and kinetic modeling provide a broader phenomenology and emerging mechanistic
      insights. CRITICAL ISSUES: Physicochemical mechanisms of the functional
      consequences of oxidative modifications of voltage-gated K+ channels are only
      beginning to be revealed. In vivo documentation of oxidative modifications of
      specific amino-acid residues of various voltage-gated K+ channel proteins,
      including the target specificity issue, is largely absent. FUTURE DIRECTIONS:
      High-resolution chemical and proteomic analysis of ion channel proteins with
      respect to oxidative modification combined with ongoing studies on channel
      structure and function will provide a better understanding of how the function of
      voltage-gated K+ channels is tuned by ROS and the corresponding reducing enzymes
      to meet cellular needs.

PMID- 24040922
TI  - Visual short-term store can compensate for a defective phonological short-term
      store in patients with apraxia of speech.
AB  - OBJECTIVE: The aim of the study was to investigate whether, within the
      phonological short-term memory (STM) system, speech articulation disorders
      primarily due to cortical damage are associated with deficits in the phonological
      recoding of visual-verbal material, and whether the visual short-term store (STS)
      can compensate for inefficient access to the phonological STS, as suggested in
      previous reports. METHOD: Two patients (AE and TM) with apraxia of speech due to
      atrophic cerebral damage were administered a battery of tasks devised to explore
      the organization of the phonological STM. RESULTS: AE's span was normal and TM's
      span was markedly reduced. Phonological similarity and word-length effects: Both
      patients showed the effects in visual presentation; the effect was less evident
      in verbal presentation. This suggests a phonological STS disorder and preserved
      rehearsal/phonological recoding, consistently with involvement of the left
      parietal regions, which was documented by the MRI in both patients. Unexpectedly,
      TM had a longer span for similar than for dissimilar words in visually presented
      stimuli. Silent phonology (on written material): At variance with controls,
      stress assignment improved during unattended speech both in AE and TM, while in
      both patients and controls a detrimental effect of unattended speech was
      documented in the initial sound task. CONCLUSIONS: To account for this unusual
      pattern of results, we hypothesized that whenever possible, AE and TM adopt the
      strategy that takes advantage of the visual STM store to compensate for a
      defective phonological STS.

PMID- 24040923
TI  - Abnormal attentional internetwork link in dyslexic readers.
AB  - OBJECTIVE: Attention ability can be divided into three separate networks
      (executive, orienting, and alerting) that differ in their function and
      neurobiology. It has been suggested that the right temporal parietal junction
      (TPJ) can gate between the orienting and the alerting systems. Because there is
      converging evidence suggesting that the right TPJ functions abnormally in
      dyslexia, the current work examines behaviorally the independence of the
      orienting and the alerting systems in dyslexic readers. METHOD: The Attention
      Network Test (ANT) is a nonlinguistic test designed to measure behaviorally the
      separate attention systems using a single test. One feature of the ANT test is
      that it captures the separability and independence of the normal attention
      networks. In the current study, dyslexic readers preformed the ANT test and their
      performance was compared with normal readers. RESULTS: Here we demonstrate,
      consistent with previous theories, impairment in executive and orienting networks
      in dyslexic readers; however, for the first time, we reveal unique situations in
      which the orienting spatial attention system in dyslexia is abnormally dependent
      on and negatively correlated with the alerting attention system. CONCLUSIONS:
      Dyslexics suffer from globally spread abnormal nonlinguistic attentional networks
      in what are considered separate attentional systems in the normal population; it
      appears that they are abnormally interrelated in the dyslexic population.

PMID- 24040921
TI  - Neuropsychological deficits associated with heavy prenatal alcohol exposure are
      not exacerbated by ADHD.
AB  - OBJECTIVE: Neuropsychological functioning of individuals with attention
      deficit/hyperactivity disorder (ADHD) or heavy prenatal alcohol exposure has been
      well documented independently. This study examined the interaction between both
      factors on cognitive performance in children. METHOD: As part of a multisite
      study, 344 children (8-16 y, M = 12.28, SD = 2.52) completed a comprehensive
      neuropsychological battery. Four subject groups were tested: children with
      histories of heavy prenatal alcohol exposure (AE) and ADHD (AE+, n = 90), alcohol
      exposed without ADHD, (AE-, n = 38), nonexposed with ADHD (ADHD, n = 80), and
      nonexposed without ADHD (CON, n = 136). RESULTS: Separate 2(AE) * 2(ADHD)
      MANCOVAs revealed significant main and interactive effects of ADHD and AE on
      overall WISC-IV, D-KEFS, and CANTAB performance. Individual ANOVAs revealed
      significant interactions on 2 WISC-IV indices [Verbal Comprehension (VCI),
      Perceptual Reasoning (PRI)], and four D-KEFS and CANTAB subtests [Design Fluency,
      Verbal Fluency, Trail Making, Spatial Working Memory]. Follow-up analyses
      demonstrated no difference between AE+ and AE- groups on these measures. The
      combined AE+/- group demonstrated more severe impairment than the ADHD group on
      VCI and PRI, but there were no other differences between clinical groups.
      CONCLUSIONS: These results support a combined AE+/- group for neuropsychological
      research and indicate that, in some cases, the neuropsychological effects seen in
      ADHD are altered by prenatal alcohol exposure. The effects of alcohol exposure on
      verbal comprehension and perceptual reasoning were greater than those related to
      having ADHD without alcohol exposure, although both conditions independently
      resulted in cognitive impairment compared to controls. Clinically, these findings
      demonstrate task-dependent patterns of impairment across clinical disorders.

PMID- 24040924
TI  - Subtle adverse effects of late preterm birth: a cautionary note.
AB  - OBJECTIVE: Late preterm birth increases risk of perinatal health complications
      that typically resolve in the short term. Thus, early elective delivery is
      thought to have no long-term effects. Whether there is increased risk of adverse
      psychological outcomes that emerge in early childhood remains uncertain. METHOD:
      The authors compared intellectual, neuropsychological, and behavioral outcomes in
      278 late preterm (35-36 weeks) and 192 term (37-41 weeks) participants at age 3
      years recruited from a single center, using analysis of variance, analysis of
      covariance, and regression analyses. Late-preterm participants were further
      subgrouped by admission to the neonatal intensive care unit (NICU; n = 202) or a
      well-baby unit (n = 76). Analyses included 132 additional participants born at 34
      weeks. RESULTS: Late preterm participants had lower general conceptual ability
      (GCA; i.e., IQ); lower verbal, nonverbal, spatial, visuomotor, and dexterity
      scores; and poorer adaptability than term participants (p < .01; -0.271 to -0.511
      SDs). Gestational age was the most important predictor of these subtle outcomes,
      not neonatal medical variables; no differences were found between NICU admitted
      and nonadmitted late-preterm groups. A 1-week increase in gestational age
      resulted in a 1.941 increase in GCA (d = 0.127). CONCLUSION: Gestation is a
      developmental continuum best not interrupted during its natural course. Our data
      showing subtle but appreciable effects have important implications for obstetric
      practice and parental decision making regarding early elective delivery in the
      absence of maternal or fetal adverse indications.

PMID- 24040926
TI  - Is emotional memory enhancement preserved in amnestic mild cognitive impairment?
      Evidence from separating recollection and familiarity.
AB  - OBJECTIVE: This study investigated whether the observed absence of emotional
      memory enhancement in recognition tasks in patients with amnestic mild cognitive
      impairment (aMCI) could be related to their greater proportion of familiarity
      based responses for all stimuli, and whether recognition tests with emotional
      items had better discriminative power for aMCI patients than those with neutral
      items. METHOD: In total, 31 aMCI patients and 30 healthy older adults
      participated in a recognition test followed by remember/know judgments. Positive,
      neutral, and negative faces were used as stimuli. RESULTS: For overall
      recognition performance, emotional memory enhancement was found only in healthy
      controls; they remembered more negative and positive stimuli than neutral ones.
      For "remember" responses, we found equivalent emotional memory enhancement in
      both groups, though a greater proportion of "remember" responses was observed in
      normal controls. For "know" responses, aMCI patients presented a larger
      proportion than normal controls did, and their "know" responses were not affected
      by emotion. A negative correlation was found between emotional enhancement effect
      and the memory performance related to "know" responses. In addition, receiver
      operating characteristic curve analysis revealed higher diagnostic accuracy for
      recognition test with emotional stimuli than with neutral stimuli. CONCLUSIONS:
      The present results implied that the absence of the emotional memory enhancement
      effect in aMCI patients might be related to their tendency to rely more on
      familiarity-based "know" responses for all stimuli. Furthermore, recognition
      memory tests using emotional stimuli may be better able than neutral stimuli to
      differentiate people with aMCI from cognitively normal older adults.

PMID- 24040925
TI  - Estimating the passage of minutes: deviant oscillatory frontal activity in
      medicated and unmedicated ADHD.
AB  - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a common and
      extensively treated psychiatric disorder in children, which often persists into
      adulthood. The core diagnostic symptoms include inappropriate levels of
      hyperactivity, impulsivity, and/or pervasive inattention. Another crucial aspect
      of the disorder involves aberrations in temporal perception, which have been well
      documented in behavioral studies and, recently, have been the focus of
      neuroimaging studies. These functional magnetic resonance imaging studies have
      shown reduced activation in anterior cingulate and prefrontal cortices in ADHD
      using a time-interval discrimination task, whereby participants distinguish
      intervals differing by only hundreds of milliseconds. METHOD: We used
      magnetoencephalography (MEG) to evaluate the cortical network serving temporal
      perception during a continuous, long-duration (in minutes) time estimation
      experiment. Briefly, medicated and unmedicated persons with ADHD, and a control
      group responded each time they estimated 60 s had elapsed for an undisclosed
      amount of time in two separate MEG sessions. All MEG data were transformed into
      regional source activity, and subjected to spectral analyses to derive amplitude
      estimates of gamma-band activity. RESULTS: Compared to controls, unmedicated
      patients were less accurate time estimators and had weaker gamma activity in the
      anterior cingulate, supplementary motor area, and left prefrontal cortex. After
      medication, these patients exhibited small but significant increases in gamma
      across these same neural regions and significant improvements in time estimation
      accuracy, which correlated with the gamma activity increases. CONCLUSION: We
      found deficient gamma activity in brain areas known to be crucial for timing
      functions, which may underlie the day-to-day abnormalities in time perception
      that are common in ADHD.

PMID- 24040927
TI  - Decision-making deficits persist after aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: Effective decision-making is critical for resuming day-to-day
      activities after aneurysmal subarachnoid hemorrhage (aSAH). Little is known,
      however, about how decision-making is affected after aSAH, particularly under
      ambiguous conditions in which neither the outcome nor the outcome probabilities
      are known. METHOD: Here we examined the integrity of decision-making under
      ambiguity in a cohort of aSAH patients classified as having made a "good outcome"
      according to the Glasgow Outcome Scale. Thirty aSAH survivors and 33 healthy
      controls completed the Iowa Gambling Task (IGT) and the Balloon Analogue Risk
      Task (BART). Mean time of assessment poststroke was 30 months. RESULTS: Although
      patients and controls had similar decision-making strategies on the IGT, patients
      made significantly fewer switches between decks, suggesting perseveration and
      cognitive inflexibility. On the BART, aSAH patients demonstrated significantly
      enhanced risk-taking behavior relative to controls. Examination of effect sizes
      revealed cognitive inflexibility in 33% to 35% of aSAH patients and enhanced risk
      taking behavior in 35% to 40% of aSAH patients. CONCLUSION: Approximately one
      third of "good outcome" aSAH patients experience cognitive inflexibility and
      enhanced risk-taking behavior over 2 years poststroke, illustrating the
      persistence of aSAH-associated cognitive impairment.

PMID- 24040928
TI  - Somatic twist: a model for the evolution of decussation.
AB  - OBJECTIVE: In the chordate and vertebrate central nervous system, sensory and
      motor nerve tracts cross from one side to the other as they connect the brain
      with sensory receptors and motor neurons. These "decussations," crossings in the
      form of an X, relate each side of the brain to the opposite side of the body. The
      protochordates derive from an invertebrate ancestor, but no such contralateral
      arrangement occurs in any invertebrate phylum. No adaptive benefit of decussation
      has been established. What might explain the evolution of decussation? METHOD: A
      brief review of relevant features of comparative morphology of invertebrates,
      chordates and vertebrates leads to an explanatory model of decussation. RESULT: A
      "somatic twist model" of invertebrate-vertebrate transition accounts for
      decussations as byproducts of a more momentous change; the relocation of the
      neuraxis from the ventral to the dorsal aspect of the body. Evidence is presented
      that this inversion proceeded by means of a twisting of the body 180 degrees on
      its axis just behind its anterior pole. This rotation aligned the neuraxis with
      the dorsal head ganglia and brain and by twisting the nerve tracts it brought
      decussation in its wake. CONCLUSION: Decussation evolved as a byproduct of a
      genetically determined partial inversion of the body plan, which resulted in a
      180 degree rotation posterior to the brain and oropharynx.

PMID- 24040930
TI  - Moral decision-making and theory of mind in patients with idiopathic Parkinson's
      disease.
AB  - OBJECTIVE: Cognitive impairments in theory of mind (ToM), executive processing,
      and decision-making are frequent and highly relevant symptoms in patients with
      Parkinson's disease (PD). These functions have been related to moral decision
      making. Their association to moral decision-making in PD, however, has not been
      studied yet. It was hypothesized that moral decisions in patients with PD differ
      from those in healthy control participants, and that more egoistic decisions are
      related to ToM as well as executive dysfunctions in patients with PD. METHOD:
      Nineteen patients with PD and 20 healthy control participants were examined with
      an everyday moral decision-making task, comprised of 10 low and 10 high emotional
      forced-choice moral dilemma short stories with egoistic and altruistic options.
      All participants received an elaborate neuropsychological test battery.
      Electrodermal skin conductance responses were recorded to examine possible
      unconscious emotional reactions during moral decision-making. RESULTS: The groups
      performed comparably in total scores of moral decision-making. Although ToM did
      not differ between groups, it was inversely related to altruistic moral decisions
      in the healthy control group, but not in patients with PD. Executive functions
      were not related to moral decision-making. No differences were found for skin
      conductance responses, yet they differed from zero in both groups. CONCLUSION:
      Our findings indicate that moral decisions do not differ between patients with PD
      and healthy control participants. However, different underlying processes in both
      groups can be presumed. While healthy control participants seem to apply ToM to
      permit egoistic moral decisions in low emotional dilemmas, patients with PD seem
      to decide independently from ToM. These mechanisms as well as neuropsychological
      and neurophysiological correlates are discussed.

PMID- 24040929
TI  - Relationship between Stroop performance and resting state functional connectivity
      in cognitively normal older adults.
AB  - OBJECTIVE: Early biomarkers of Alzheimer's disease (AD) are needed for developing
      therapeutic interventions. Measures of attentional control in Stroop-type tasks
      discriminate healthy aging from early stage AD and predict future development of
      AD in cognitively normal individuals. Disruption in resting state functional
      connectivity MRI (rs-fcMRI) has been reported in AD and in healthy controls at
      risk for AD. We explored the relationship among Stroop performance, rs-fcMRI, and
      CSF Abeta42 levels in cognitively normal older adults. METHOD: A computerized
      Stroop task (along with standard neuropsychological measures), rs-fcMRI, and CSF
      were obtained in 237 cognitively normal older adults. We compared the
      relationship between Stroop performance, including measures from reaction
      distributional analyses, and composite scores from four resting state networks
      (RSNs; default mode [DMN], salience [SAL], dorsal attention [DAN], and sensory
      motor [SMN]), and the modulatory influence of CSF Abeta42 levels. RESULTS: A
      larger Stroop effect in errors was associated with reduced rs-fcMRI within the
      DMN and SAL. Reaction time (RT) distributional analyses indicated the slow tail
      of the RT distribution was related to reduced rs-fcMRI functional connectivity
      within the SAL. Standard psychometric measures were not related to RSN composite
      scores. A relationship between Stroop performance and DMN (but not SAL)
      functional connectivity was stronger in CSF Abeta42-positive individuals.
      CONCLUSIONS: A link exists between RSN composite scores and specific attentional
      performance measures. Both measures may be sensitive biomarkers for AD.

PMID- 24040931
TI  - Is social attention impaired in schizophrenia? Gaze, but not pointing gestures,
      is associated with spatial attention deficits.
AB  - OBJECTIVE: The nature of possible impairments in orienting attention to social
      signals in schizophrenia is controversial. The present research was aimed at
      addressing this issue further by comparing gaze and arrow cues. Unlike previous
      studies, we also included pointing gestures as social cues, with the goal of
      addressing whether any eventual impairment in the attentional response was
      specific to gaze signals or reflected a more general deficit in dealing with
      social stimuli. METHOD: Patients with schizophrenia or schizoaffective disorder
      and matched controls performed a spatial-cuing paradigm in which task-irrelevant
      centrally displayed gaze, pointing finger, and arrow cues oriented rightward or
      leftward, preceded a lateralized target requiring a simple detection response.
      RESULTS: Healthy controls responded faster to spatially congruent targets than to
      spatially incongruent targets, irrespective of cue type. In contrast,
      schizophrenic patients responded faster to spatially congruent targets than to
      spatially incongruent targets only for arrow and pointing finger cues. No cuing
      effect emerged for gaze cues. CONCLUSION: The results support the notion that
      gaze cuing is impaired in schizophrenia, and suggest that this deficit may not
      extend to all social cues.

PMID- 24040933
TI  - In vivo characterization of the properties of SUMO1-specific monobodies.
AB  - Monobodies are small recombinant proteins designed to bind with high affinity to
      target proteins. Monobodies have been generated to mimic the SIM [SUMO (small
      ubiquitin-like modifier)-interacting motif] present in many SUMO target proteins,
      but their properties have not been determined in cells. In the present study we
      characterize the properties of two SUMO1-specific monobodies (hS1MB4 and hS1MB5)
      in HEK (human embyronic kidney)-293 and HeLa cells and examine their ability to
      purify SUMO substrates from cell lines and rat brain. Both hS1MB4 and hS1MB5
      compared favourably with commercially available antibodies and were highly
      selective for binding to SUMO1 over SUMO2/3 in pull-down assays against
      endogenous and overexpressed SUMO and SUMOylated proteins. Monobodies expressed
      in HeLa cells displayed a nuclear and cytosolic distribution that overlaps with
      SUMO1. Expression of the monobodies effectively inhibited protein SUMOylation by
      SUMO1 and, surprisingly, by SUMO2/3, but were not cytotoxic for at least 36 h. We
      attribute the effects on SUMO2/3 to the role of SUMO1 in chain termination and/or
      monobody inhibition of the SUMO-conjugating E1 enzyme complex. Taken together,
      these data provide the first demonstration that monobodies represent useful new
      tools both to isolate SUMO conjugates and to probe cell SUMOylation pathways in
      vivo.

PMID- 24040932
TI  - Palladium(III)-catalyzed fluorination of arylboronic acid derivatives.
AB  - A practical, palladium-catalyzed synthesis of aryl fluorides from arylboronic
      acid derivatives is presented. The reaction is operationally simple and amenable
      to multigram-scale synthesis. Evaluation of the reaction mechanism suggests a
      single-electron-transfer pathway, involving a Pd(III) intermediate that has been
      isolated and characterized. 

PMID- 24040934
TI  - Homogeneous surface oxidation of organosilicates by controlled combustion of
      adsorbed fuels: a facile method for low-temperature processing.
AB  - We have developed a method for the oxidation of organosilicate materials at
      temperatures considerably lower than those typically required for uncatalyzed
      oxidation. The process utilizes a combustible fuel delivered to the surface in an
      oxidizing environment to locally oxidize materials with carbon-silicon bonds. It
      also provides a level of control that cannot be achieved through standard high
      energy top-to-bottom oxidative procedures such as UV-ozone and O2 plasmas. While
      the latter processes attack the outer interface, local oxidation can be achieved
      using our process by manipulating the distribution of the combustible fuel. We
      use this technique to generate oxidized porous organosilicate films with either a
      sharp oxidation front or uniform oxidation where the relative carbon content can
      be controlled through the film thickness depending on processing conditions.
      Further, we show that this process can also be used to seal bulk interconnected
      microporosity in films (<1 nm) without substantially changing the refractive
      index of the material. For both the nominally dense and porous films, the surface
      oxidation is accompanied by an increase in the Young's modulus and the oxidized
      films can be readily functionalized using standard silane chemistry to provide a
      variety of chemical functionalities. 

PMID- 24040935
TI  - Space survivable polyimides with excellent optical transparency and self-healing
      properties derived from hyperbranched polysiloxane.
AB  - A novel space survivable polyimide with a variety of desirable properties such as
      excellent thermal stability, high optical transparency, good mechanical strength,
      satisfactory break elongation, and outstanding atomic oxygen (AO) erosion
      resistance has been prepared by first synthesizing hyperbranched polysiloxane
      (HBPSi) and second incorporating HBPSi into polyimide (PI) chains via
      copolycondensation reactions. The 29Si nuclear magnetic resonance (29Si NMR)
      spectrum of HBPSi indicated that HBPSi possessed hyperbranched topology. The
      ground-based simulated AO exposure experiments demonstrated the mass loss of
      HBPSi polyimides decreased with increasing HBPSi addition and AO fluence, and it
      reached as low as 7.7% that of pristine polyimide when HBPSi addition was 29.7 wt
      % after 22 h AO exposure. Surface morphologies confirmed that pristine polyimide
      was significantly roughened after AO exposure while HBPSi polyimide had even less
      rough surface topography. During exposure of HBPSi polyimide to AO, the organic
      polyimide of the surface was first degraded and a silica protective layer
      eventually formed, which enabled the surface to be "self-healing". It is this
      passivation layer that prevents the underlying polymer from additional erosion.
      The whole preparation process of HBPSi polyimide is moderate, low-cost,
      environmentally friendly, and suitable for industrialized mass production, which
      contributes this novel material to a "drop-in" replacement for the widely used
      Kapton on spacecrafts functioning in space environment.

PMID- 24040936
TI  - Influence of mileage accumulation on the particle mass and number emissions of
      two gasoline direct injection vehicles.
AB  - Gasoline direct injection (GDI) is a new engine technology intended to improve
      fuel economy and greenhouse gas emissions as required by recently enacted
      legislative and environmental regulations. The development of this technology
      must also ensure that these vehicles meet new LEV III and Tier 3 emissions
      standards as they phase in between 2017 and 2021. The aim of the present paper is
      to examine, at least for a small set, how the PM emissions from GDI vehicles
      change over their lifetime. The paper reports particle mass and number emissions
      of two GDI vehicles as a function of mileage up to 150K miles. These vehicles
      exhibit PM emissions that are near or below the upcoming 3 mg/mi FTP and 10 mg/mi
      US06 mass standards with little, if any, deterioration over 150K miles. Particle
      number emissions roughly follow the previously observed 2 * 10(12) particles/mg
      correlation between solid particle number and PM mass. They remained between the
      interim and final EU stage 6 solid particle count standard for gasoline vehicles
      throughout the mileage accumulation study. These examples demonstrate feasibility
      to meet near-term 3 mg/mi and interim EU solid particle number standards, but
      continued development is needed to ensure that this continues as further fuel
      economy improvements are made. 

PMID- 24040937
TI  - EVEREST II high risk study based UK cost-effectiveness analysis of MitraClip(r)
      in patients with severe mitral regurgitation ineligible for conventional
      repair/replacement surgery.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of MitraClip, an interventional
      procedure for patients with chronic severe mitral regurgitation. METHODS: A
      decision analytic model with a lifetime horizon was developed to assess the cost
      effectiveness of MitraClip vs conventional medical management in patients with
      severe mitral regurgitation, ineligible for surgery. The analysis was performed
      from a UK NHS perspective and the estimates for mortality, adverse events, and
      cross-sectional NYHA class were obtained from the EVEREST II High Risk Study
      (HRS). Utility decrements were obtained from a heath technology assessment on
      Cardiac Resynchronization Therapy, while unit costs were obtained from national
      databases. The concept model was clinically validated. Costs (2011 LUK) and
      benefits were discounted at an annual rate of 3.5%. RESULTS: Compared to medical
      management, over 2- and 10-year periods MitraClip had incremental Quality
      Adjusted Life Year (QALY) gains of 0.48 and 2.04, respectively. The Incremental
      Cost-Effectiveness Ratios for MitraClip at 2 and 10 years are L52,947 and L14,800
      per QALY gained. Overall, the model was most sensitive to the choice of time
      horizon, the discount rate applied to benefits, the starting age of cohort, the
      utility decrement associated with NYHA II, and cost of the MitraClip procedure.
      The model was insensitive to changes in all other parameters. MitraClip was also
      found to be cost-effective, regardless of the modelling approach, and insensitive
      to the key assumptions of the procedure cost. STUDY LIMITATIONS: The primary
      limitation of the analysis is the reliance on aggregate data from a modestly
      sized non-randomized study with a short-term follow-up period. Aligned to this
      was the need to extrapolate survival well beyond the study period in order to
      generate meaningful results. The impact of both of these limitations was explored
      via extensive sensitivity analyses. CONCLUSION: Compared to medical management,
      MitraClip is a cost-effective interventional procedure at conventional threshold
      values.

PMID- 24040938
TI  - Sleep disturbances associated with cigarette smoking.
AB  - Sleep disturbances resulting in insufficient sleep have been linked to negative
      physical, cognitive, and public health outcomes. Despite this, there has yet a
      study that examines the impact of smoking on sleep in a US based national sample.
      The current study sought to observe sleep disturbances associated with smoking
      status. Sleep disturbances in adults aged 20 years and above, from the 2005-2006
      National Health and Nutrition Examination Survey, were measured among current,
      former, and never smokers (NS). Current smokers (CS) reported significantly less
      total sleep time, longer sleep onset latency, increased difficulty falling
      asleep, maintaining sleep, and waking up earlier than desired when compared to
      NS. Former smokers reported disturbances similar to NS and CS experienced poorer
      sleep than nonsmokers. Our study is the first to observe sleep difficulty by
      smoking status in a large, population-based, nationally representative sample.
      Recommendations for smoking cessation programs are discussed. 

PMID- 24040941
TI  - Alteration of skin perfusion in mottling area during septic shock.
AB  - BACKGROUND: Mottling score has been reported to be a strong predictive factor
      during septic shock. However, the pathophysiology of mottling remains unclear.
      METHODS: In patients admitted in ICU for septic shock, we measured on the same
      area the mean skin perfusion by laser Doppler, the mottling score, and variations
      of both indices between T1 (6 hours after vasopressors were started) and T2 (24
      hours later). RESULTS: Fourteen patients were included, SAPS II was 56 [37-71]
      and SOFA score at T1 was 10 [7-12]. The mean skin surface area analyzed was 4108
      +/- 740 mm2; 1184 +/- 141 measurements were performed over each defined skin
      surface area. Skin perfusion was significantly different according to mottling
      score and decreased from 37 [31-42] perfusion units (PUs) for a mottling score of
      [0-1] to 22 [20-32] PUs for a mottling score of [2-3] and 23 [16-28] for a score
      of [4-5] (Kruskal-Wallis test, P = 0.05). We analyzed skin perfusion changes
      during resuscitation in each patient and together with mottling score variations
      between T1 and T2 using a Wilcoxon signed-rank test. Among the 14 patients
      included, mottling score increased (worsened) in 5 patients, decreased (improved)
      in 5 patients, and remained stable in 4 patients. Baseline skin perfusion at T1
      was arbitrarily scored 100%. Mean skin perfusion significantly decreased in all
      the patients whose mottling score worsened from 100% baseline to 63.2 +/- 10.7%
      (P = 0.001), mean skin perfusion significantly increased in all patients whose
      mottling score improved from 100% baseline to 172.6 +/- 46.8% (P = 0.001), and
      remained stable in patients whose mottling score did not change (100.5 +/- 6.8%,
      P = 0.95). CONCLUSIONS: We have shown that mottling score variations and skin
      perfusion changes during septic shock resuscitation were correlated, providing
      additional evidence that mottling reflects skin hypoperfusion.

PMID- 24040940
TI  - Molecular-guided therapy predictions reveal drug resistance phenotypes and
      treatment alternatives in malignant peripheral nerve sheath tumors.
AB  - BACKGROUND: Malignant peripheral nerve sheath tumors (MPNST) are rare highly
      aggressive sarcomas that affect 8-13% of people with neurofibromatosis type 1.
      The prognosis for patients with MPNST is very poor. Despite TOP2A overexpression
      in these tumors, doxorubicin resistance is common, and the mechanisms of
      chemotherapy resistance in MPNST are poorly understood. Molecular-guided therapy
      prediction is an emerging strategy for treatment refractory sarcomas that
      involves identification of therapy response and resistance mechanisms in
      individual tumors. Here, we report the results from a personalized, molecular
      guided therapy analysis of MPNST samples. METHODS: Established molecular-guided
      therapy prediction software algorithms were used to analyze published microarray
      data from human MPNST samples and cell lines, with benign neurofibroma tissue
      controls. MPNST and benign neurofibroma-derived cell lines were used for
      confirmatory in vitro experimentation using quantitative real-time PCR and growth
      inhibition assays. Microarray data was analyzed using Affymetrix expression
      console MAS 5.0 method. Significance was calculated with Welch's t-test with non
      corrected p-value < 0.05 and validated using permutation testing across samples.
      Paired Student's t-tests were used to compare relative EC50 values from
      independent growth inhibition experiments. RESULTS: Molecular guided therapy
      predictions highlight substantial variability amongst human MPNST samples in
      expression of drug target and drug resistance pathways, as well as some
      similarities amongst samples, including common up-regulation of DNA repair
      mechanisms. In a subset of MPNSTs, high expression of ABCC1 is observed, serving
      as a predicted contra-indication for doxorubicin and related therapeutics in
      these patients. These microarray-based results are confirmed with quantitative,
      real-time PCR and immunofluorescence. The functional effect of drug efflux in
      MPNST-derived cells is confirmed using in vitro growth inhibition assays.
      Alternative therapeutics supported by the molecular-guided therapy predictions
      are reported and tested in MPNST-derived cells. CONCLUSIONS: These results
      confirm the substantial molecular heterogeneity of MPNSTs and validate molecular
      guided therapy predictions in vitro. The observed molecular heterogeneity in
      MPNSTs influences therapy prediction. Also, mechanisms involving drug transport
      and DNA damage repair are primary mediators of MPNST chemotherapy resistance.
      Together, these findings support the utility of individualized therapy in MPNST
      as in other sarcomas, and provide initial proof-of concept that individualized
      therapy prediction can be accomplished.

PMID- 24040943
TI  - Use of brain electrical activity for the identification of hematomas in mild
      traumatic brain injury.
AB  - This study investigates the potential clinical utility in the emergency
      department (ED) of an index of brain electrical activity to identify intracranial
      hematomas. The relationship between this index and depth, size, and type of
      hematoma was explored. Ten minutes of brain electrical activity was recorded from
      a limited montage in 38 adult patients with traumatic hematomas (CT scan
      positive) and 38 mild head injured controls (CT scan negative) in the ED. The
      volume of blood and distance from recording electrodes were measured by blinded
      independent experts. Brain electrical activity data were submitted to a
      classification algorithm independently developed traumatic brain injury (TBI)
      index to identify the probability of a CT+traumatic event. There was no
      significant relationship between the TBI-Index and type of hematoma, or distance
      of the bleed from recording sites. A significant correlation was found between
      TBI-Index and blood volume. The sensitivity to hematomas was 100%, positive
      predictive value was 74.5%, and positive likelihood ratio was 2.92. The TBI
      Index, derived from brain electrical activity, demonstrates high accuracy for
      identification of traumatic hematomas. Further, this was not influenced by
      distance of the bleed from the recording electrodes, blood volume, or type of
      hematoma. Distance and volume limitations noted with other methods, (such as that
      based on near-infrared spectroscopy) were not found, thus suggesting the TBI
      Index to be a potentially important adjunct to acute assessment of head injury.
      Because of the life-threatening risk of undetected hematomas (false negatives),
      specificity was permitted to be lower, 66%, in exchange for extremely high
      sensitivity.

PMID- 24040942
TI  - Small-molecule ligands of methyl-lysine binding proteins: optimization of
      selectivity for L3MBTL3.
AB  - Lysine methylation is a key epigenetic mark, the dysregulation of which is linked
      to many diseases. Small-molecule antagonism of methyl-lysine (Kme) binding
      proteins that recognize such epigenetic marks can improve our understanding of
      these regulatory mechanisms and potentially validate Kme binding proteins as drug
      discovery targets. We previously reported the discovery of 1 (UNC1215), the first
      potent and selective small-molecule chemical probe of a methyl-lysine reader
      protein, L3MBTL3, which antagonizes the mono- and dimethyl-lysine reading
      function of L3MBTL3. The design, synthesis, and structure-activity relationship
      studies that led to the discovery of 1 are described herein. These efforts
      established the requirements for potent L3MBTL3 binding and enabled the design of
      novel antagonists, such as compound 2 (UNC1679), that maintain in vitro and
      cellular potency with improved selectivity against other MBT-containing proteins.
      The antagonists described were also found to effectively interact with unlabeled
      endogenous L3MBTL3 in cells. 

PMID- 24040944
TI  - Minimally invasive sacroiliac joint fusion: one-year outcomes in 18 patients.
AB  - BACKGROUND: Sacroiliac joint (SI) pain is an often-overlooked cause of low back
      pain due, in part, to lack of specific findings on radiographs and symptoms
      mimicking other back-related disorders. We report our experience with minimally
      invasive (MIS) SI joint arthrodesis using a series of triangular, titanium plasma
      spray (TPS) coated implants in patients refractory to conservative care. METHODS:
      We report outcomes from 18 patients with 12 months of postoperative follow
      up.Demographics, complications, and clinical outcomes using visual analog scale
      (VAS) for pain, Oswestry Disability Index (ODI) for back function and SF-12 for
      quality of life were collected preoperatively and at 3, 6 and 12 months post
      operatively. RESULTS: Mean age was 64 years and 67% of patients were female.
      There were no intraoperative complications and one explant at three months for
      malposition.All patient-reported outcomes showed both clinically and
      statistically significant improvement at 12 months (p < 0.001 for each of the
      following): VAS improved by 6.6 points, ODI scores improved by -37.5 points. One
      year SF-12 physical and mental component (PCS, MCS) scores approximated
      population normal scores for both physical and mental functioning. Patient
      satisfaction with outcomes was high at 95%; 89% said would have the same surgery
      again. CONCLUSIONS: MIS SI joint fusion using a series of triangular porous TPS
      coated titanium implants is a safe and effective procedure for patients with SI
      joint disorders who have failed conservative care.

PMID- 24040946
TI  - Important take-aways from the Boston marathon bombing.

PMID- 24040945
TI  - Altered expression of caveolin 2 and 3 in smooth muscle of rat urinary bladder by
      17beta-estradiol.
AB  - BACKGROUND: The purpose of this study was to investigate the effect of estrogen
      alteration on the expression of caveolin 2 and 3 in rat smooth muscle of urinary
      bladder. METHODS: Female Sprague-Dawley rats were divided into three groups:
      control, bilateral ovariectomy (Ovx), and bilateral ovariectomy followed by
      subcutaneous injections of 17beta-estradiol (Ovx+Est). After 4 weeks, urodynamic
      measurements were taken to ascertain the contraction interval and contraction
      pressure. The expression and cellular localization of caveolin 2 and 3 were
      determined by Western blot and immunohistochemistry in rat urinary bladder smooth
      muscle. RESULTS: In cystometrograms, the contraction interval (min) was
      significantly lower in the Ovx group (3.1+/-1.5) than in the control group (5.6+/
      1.2), but was increased after estrogen treatment (9.3+/-1.0). Conversely, the
      average contraction pressure (mmHg) was higher in the Ovx group (26.2+/-2.3) than
      in the control group (21.9+/-3.1), and was decreased after estrogen treatment
      (23.8+/-3.5). Caveolin 2 and 3 expression was localized in the cell membrane of
      the smooth muscle. The protein expression of both caveolin 2 and 3 was
      significantly lower after ovariectomy and was restored to the control levels
      after 17beta-estradiol treatment. CONCLUSIONS: Hormonal alteration causes a
      significant change in the expression of caveolin 2 and 3 in smooth muscle of rat
      urinary bladder. These findings suggest that these molecules might have
      functional roles in the detrusor overactivity that occurs in association with
      hormonal alteration.

PMID- 24040947
TI  - Infiltration anesthesia for extraction of the mandibular molars.
AB  - PURPOSE: Profound anesthesia for mandibular molars by buccal infiltration has
      been tried in recent years, with promising results. This prospective, randomized,
      single-blinded, crossover study investigated the clinical anesthetic efficacy
      obtained with 1:100,000 epinephrine plus 4% articaine (A100) 1.8 versus 3.6 mL as
      mandibular first molar buccal infiltration during removal of impacted lower third
      molars. MATERIALS AND METHODS: Thirty adult patients underwent removal of
      symmetrically positioned impacted lower third molars in 2 separate appointments.
      The patients randomly received mandibular buccal first molar infiltration of A100
      1.8 or 3.6 mL during surgery. For assessment of anesthetic efficacy, any pain
      during surgery was rated using the visual analog scale. Also, the onset,
      duration, and total amount of anesthetic used were recorded. RESULTS: Compared
      with the 1.8-mL volume of A100, the 3.6-mL volume showed a statistically higher
      success rate (93% vs 56%). CONCLUSIONS: Infiltration in the buccal vestibule
      opposite the mandibular first molar by A100 3.6 mL may be a good option for
      extraction of mandibular third molars, with supplemental lingual anesthesia.

PMID- 24040948
TI  - Transplantation of human dental pulp stem cells: enhance bone consolidation in
      mandibular distraction osteogenesis.
AB  - PURPOSE: The main aim of the present study was to evaluate the capacity of stem
      cells from human exfoliated deciduous teeth (SHED) to enhance mandibular
      distraction osteogenesis (DO) in rabbits. MATERIALS AND METHODS: A randomized
      controlled trial was conducted. Eighteen skeletally immature New Zealand white
      rabbits were divided into 2 groups, with 9 in the control group and 9 in the SHED
      group. The SHED were isolated, expanded, and characterized. Six million cells
      were transplanted into the distracted area during the osteotomy period. After a 4
      day latency period, a total of 6 mm was distracted for 6 days. The newly formed
      bone was analyzed radiologically, histologically, and histomorphometrically at 2,
      4, and 6 weeks postoperatively. Nonparametric analysis of variance (Kruskal
      Wallis test) was used for data analysis, and P < .05 was considered statistically
      significant. RESULTS: The cell lineage was positive for the 2 mesenchymal stem
      cell markers tested (CD105 and CD166). More mature bone in the SHED transplanted
      group was observed radiographically and histologically. Histomorphologically, the
      percentage of newly formed bone after 2, 4, and 6 weeks was 18.41% and 41.53%,
      31.68% and 59.78%, and 52.34% and 65.24% in the control and SHED groups,
      respectively. The difference between the groups was statistically significant (P
      = .012). The bone union and stage of bone maturity scores were significantly
      different between the control and SHED groups (P = .006 and P = .011,
      respectively). CONCLUSIONS: Our findings suggest that SHED can serve as an
      additional cell resource for DO enhancement in rabbits and might be a promising
      model for the reconstruction of large mandibular defects in human oral
      maxillofacial surgery.

PMID- 24040950
TI  - Psychometric properties of the Brazilian version of the Orthognathic Quality of
      Life Questionnaire.
AB  - PURPOSE: To assess the construct validity and reliability of the Brazilian
      version of the Orthognathic Quality of Life Questionnaire (B-OQLQ). MATERIALS AND
      METHODS: A cross-sectional study was performed, and 101 patients in need of
      orthodontic-surgical treatment were recruited at a public hospital (Hospital
      Universitario Pedro Ernesto) and a public dental school (Faculdade de Odontologia
      da Universidade do Estado do Rio de Janeiro). The B-OQLQ was self-completed. The
      mean age of the participants was 26.51 +/- 9.25 years, and most were female
      (58.42%; n = 59). The construct validity was assessed using Spearman's
      correlation coefficient between the B-OQLQ and the Oral Health Impact Profile
      (OHIP-14) scores and between the B-OQLQ and subjective health indicators' scores.
      The reliability was assessed in terms of internal consistency and stability (test
      retest) using Cronbach's alpha and the intraclass correlation coefficient (ICC),
      respectively. RESULTS: Significant correlations were found between the B-OQLQ
      scores and the following: OHIP-14 total score (rs = 0.70, P < .001), perception
      of oral health (rs = -0.24, P = .02), single-item evaluation of quality of life
      (rs = -0.29, P = .03), satisfaction with physical appearance (rs = -0.40, P <
      .001), and satisfaction with facial appearance (rs = -0.39, P = .0001).
      Cronbach's alpha and the ICC was 0.95 and 0.90, respectively. The domains of B
      OQLQ causing the most effect on the quality of life included "social aspects of
      deformity" (13.0 +/- 10.54) and "facial aesthetics" (11.81 +/- 6.23).
      CONCLUSIONS: The Brazilian version of the OQLQ was shown to be valid and reliable
      with good psychometric properties and might thus be considered an appropriate
      tool to assess the effect of dentofacial deformities on the quality of life of
      individuals with this condition.

PMID- 24040949
TI  - Temporomandibular joint condylar changes following maxillomandibular advancement
      and articular disc repositioning.
AB  - PURPOSE: To evaluate condylar changes 1 year after bimaxillary surgical
      advancement with or without articular disc repositioning using longitudinal
      quantitative measurements in 3-dimensional (3D) temporomandibular joint (TMJ)
      models. METHODS: Twenty-seven patients treated with maxillomandibular advancement
      (MMA) underwent cone-beam computed tomography before surgery, immediately after
      surgery, and at 1-year follow-up. All patients underwent magnetic resonance
      imaging before surgery to assess disc displacements. Ten patients without disc
      displacement received MMA only. Seventeen patients with articular disc
      displacement received MMA with simultaneous TMJ disc repositioning (MMA-Drep).
      Pre- and postsurgical 3D models were superimposed using a voxel-based
      registration on the cranial base. RESULTS: The location, direction, and magnitude
      of condylar changes were displayed and quantified by graphic semitransparent
      overlays and 3D color-coded surface distance maps. Rotational condylar
      displacements were similar in the 2 groups. Immediately after surgery, condylar
      translational displacements of at least 1.5 mm occurred in a posterior, superior,
      or mediolateral direction in patients treated with MMA, whereas patients treated
      with MMA-Drep presented more marked anterior, inferior, and mediolateral condylar
      displacements. One year after surgery, more than half the patients in the 2
      groups presented condylar resorptive changes of at least 1.5 mm. Patients treated
      with MMA-Drep presented condylar bone apposition of at least 1.5 mm at the
      superior surface in 26.4%, the anterior surface in 23.4%, the posterior surface
      in 29.4%, the medial surface in 5.9%, or the lateral surface in 38.2%, whereas
      bone apposition was not observed in patients treated with MMA. CONCLUSIONS: One
      year after surgery, condylar resorptive changes greater than 1.5 mm were observed
      in the 2 groups. Articular disc repositioning facilitated bone apposition in
      localized condylar regions in patients treated with MMA-Drep.

PMID- 24040939
TI  - RNA polymerase II C-terminal domain: Tethering transcription to transcript and
      template.

PMID- 24040951
TI  - Rapid and accurate identification of cut ends of facial nerves using a nerve
      monitoring system during surgical exploration and anastomosis.
AB  - PURPOSE: Surgical exploration and end-to-end neurorrhaphy is the preferred
      management for traumatic facial nerve injury. Traditionally, finding the cut ends
      of facial nerves depends mainly on a surgeon's experience. In this study, a nerve
      monitoring system to help the surgeon quickly and accurately identify, confirm,
      and locate the cut ends of facial nerve branches was investigated. PATIENTS AND
      METHODS: Six patients with traumatic facial nerve injury were selected, and the
      nerve monitoring system was applied during the surgical process of facial nerve
      exploration and anastomosis. Operation time and surgical outcome were used to
      evaluate the effect of this method. RESULTS: The surgical procedures required 6
      to 15 minutes (mean, 10 minutes) for detecting and dissecting each cut end of a
      facial nerve branch. All cut ends of injured facial nerve branches were found
      during surgery in all 6 patients, and no intraoperative complications were
      encountered. The postoperative function of the facial nerve, evaluated by
      clinical examination and diagnostic electroneurography, was satisfactory and
      symmetrical in all 6 patients at 3 months. CONCLUSION: Using a nerve monitoring
      system could effectively help surgeons achieve rapid and accurate identification
      of the cut ends of facial nerves during surgical facial nerve exploration for
      traumatic facial nerve injury.

PMID- 24040952
TI  - Reconstructing a full-thickness cheek defect of electrical burn with a folding
      radial forearm flap.
AB  - A 42-year-old male patient sustained severe burns from 10-kV, high-voltage
      electricity on his right cheek. The wound on the right cheek was 12 * 10 cm and
      was connected to the oral cavity. The teeth, gums, and mandible were exposed. A
      left radial forearm free flap was designed according to the size and shape of the
      cheek wound. The superficial portion of the flap was 13 * 9.5 cm, and the lining
      portion of the flap, replacing the oral mucosa, was 6 * 5 cm. The end of the
      radial artery was anastomosed to the facial artery contralaterally through a
      subcutaneous tunnel under his jaw, because the ipsilateral facial artery had been
      injured. The end of the radial vein was anastomosed to the external jugular vein
      ipsilaterally. In conclusion, free folding radial forearm flaps could be a good
      alternative for reconstruction of full-thickness defects of the cheek. 

PMID- 24040953
TI  - Metastatic renal cell carcinoma of the posterior nasal septum as the first
      presentation 10 years after nephrectomy.
AB  - Metastasis of renal cell carcinoma (RCC) to the head and neck region is
      infrequent, and metastatic RCC in the nasal cavity and paranasal sinuses is rare.
      Although there are reported cases of RCC to the paranasal sinuses, isolated
      metastasis of RCC to the nasal septum is extremely rare. This report describes a
      case of metastatic RCC of the posterior nasal septum that presented as severe
      epistaxis in a patient who underwent nephrectomy for RCC 10 years previously. 

PMID- 24040954
TI  - Effects of gaseous atmosphere and antioxidants on the development and
      cryotolerance of bovine embryos at different periods of in vitro culture.
AB  - This study examined the effects of antioxidant supplementation and O2 tension on
      embryo development, cryotolerance and intracellular reactive oxygen species (ROS)
      levels. The antioxidant supplementation consisted of 0.6 mM cysteine (CYST); 0.6
      mM cysteine + 100 MUM cysteamine (C+C); 100 IU catalase (CAT) or 100 MUM beta
      mercaptoethanol (beta-ME) for 3 or 7 days of in vitro culture (IVC). Two O2
      tensions (20% O2 [5% CO2 in air] or 7% O2, 5% CO2 and 88% N2 [gaseous mixture])
      were examined. After 7 days of antioxidant supplementation, the blastocyst
      frequencies were adversely affected (P < 0.05) by CYST (11.2%) and C+C (1.44%),
      as well as by low O2 tension (17.2% and 11.11% for 20% and 7% O2, respectively)
      compared with the control (26.6%). The blastocyst re-expansion rates were not
      affected (P > 0.05) by the treatments (range, 66-100%). After 3 days of
      antioxidant supplementation, the blastocyst frequencies were not affected (P >
      0.05) by any of the antioxidants (range, 43.6-48.5%), but they were reduced by
      low O2 tension (P < 0.05) (52.1% and 38.4% for 20% and 7% O2, respectively). The
      intracellular ROS levels, demonstrated as arbitrary fluorescence units, were not
      affected (P > 0.05) by antioxidant treatment (range, 0.78 to 0.95) or by O2
      tension (0.86 and 0.88 for 20% and 7% O2, respectively). The re-expansion rates
      were not affected (P > 0.05) by any of the treatments (range, 63.6-93.3%). In
      conclusion, intracellular antioxidant supplementation and low O2 tension
      throughout the entire IVC period were deleterious to embryo development. However,
      antioxidant supplementation up to day 3 of IVC did not affect the blastocyst
      frequencies or intracellular ROS levels. 

PMID- 24040955
TI  - Increasing the gravimetric energy density of organic based secondary battery
      cathodes using small radius cations (Li+ and Mg2+).
AB  - One of the major challenges in electrochemical energy storage (EES) is increasing
      the gravimetric capacity and energy density of the cathode material. Here we
      demonstrate how to increase the gravimetric energy density of electrical energy
      storage devices based on the use of organic materials through exploitation of the
      strong ionic coupling between a reduced carbonyl functionality and small cations
      such as lithium (Li(+)) and magnesium (Mg(2+)). Binding of the cation to the
      reduced carbonyl results in a positive shift of the formal reduction potential of
      the carbonyl couple. This has the effect of increasing the cell voltage which, in
      turn, results in an increase in the energy density. We show how this interaction
      can be used to dramatically increase, by up to a factor of 2, the energy density
      for a selected case study using 1,2-di(thiophen-2-yl)ethane-1,2-dione (DTED). We
      have carried out electrochemical and computational studies in order to understand
      the thermodynamic (positive shift of 250 mV and 1 V in the formal potential for
      the first and second reductions, respectively, of the carbonyl groups of DTED)
      and kinetic effects between small radii cations (Li(+) and Mg(2+)) and the
      reduced carbonyl functionality of carbonyl-based organic molecules (C-bOMs). 

PMID- 24040956
TI  - The role of empathy in promoting change.
AB  - Since Rogers identified empathy as an important variable in therapy, it has been
      found to be a consistent predictor of client change; less clear is how this
      occurs. The objective in this study was to test a mediation model to determine
      whether clients' self-reported experience of therapists' empathy contributed to
      changes in their attachment styles and treatment of self, after 16 weeks of
      psychotherapy for depression. There was a significant direct relationship between
      therapists' empathy and outcome and a significant indirect effect, showing that
      clients' perceptions of therapists' empathy was associated with significant
      improvement in attachment insecurity and significant decreases in negative self
      treatment at the end of therapy as well as reductions on BDI, IIP, DAS and SCL-90
      R, GSI, and increases on RSE. The findings suggest that clients' perception of
      their therapists as empathic is an important mechanism of change in psychotherapy
      that warrants further investigation.

PMID- 24040958
TI  - Effect of biointerfacing linker chemistries on the sensitivity of silicon
      nanowires for protein detection.
AB  - Point-of-care diagnostics show promise in removing reliance on centralized lab
      testing facilities and may help increase both the survival rate for infectious
      diseases as well as monitoring of chronic illnesses. CMOS compatible diagnostic
      platforms are currently being considered as possible solutions as they can be
      easily miniaturized and can be cost-effective. Top-down fabricated silicon
      nanowires are a CMOS-compatible technology which have demonstrated high
      sensitivities in detecting biological analytes, such as proteins, DNA, and RNA.
      However, the reported response of nanowires to these analytes has varied widely
      since several different functionalization protocols have been attempted with
      little characterization and comparison. Here we report protocols for fabrication
      and functionalization of silicon nanowires which yield highly stable nanowires in
      aqueous solutions and limits of detection to ~1 pg/mL of the model protein used
      in the study. A thorough characterization was done into optimizing the release of
      the silicon nanowires using combined dry and wet etch techniques, which yielded
      nanowires that could be directly compared to increase output statistics.
      Moreover, a range of different linker chemistries were tried for reacting the
      primary antibody, and its response to target and nonspecific antigens, with
      polyethylene glycol based linker BS(PEG)5 providing the best response.
      Consequently, this chemistry was used to characterize different oxide thicknesses
      and their responses to the mouse IgG antigen, which with the smallest oxide
      thickness yielded 0.1-1 pg/mL limits of detection and a dynamic range over 3
      orders of magnitude. 

PMID- 24040959
TI  - Total synthesis, relay synthesis, and structural confirmation of the C18
      norditerpenoid alkaloid neofinaconitine.
AB  - The first total synthesis of the C18-norditerpenoid aconitine alkaloid
      neofinaconitine and relay syntheses of neofinaconitine and 9-deoxylappaconitine
      from condelphine are reported. A modular, convergent synthetic approach involves
      initial Diels-Alder cycloaddition between two unstable components, cyclopropene
      10 and cyclopentadiene 11. A second Diels-Alder reaction features the first use
      of an azepinone dienophile (8), with high diastereofacial selectivity achieved
      via rational design of siloxydiene component 36 with a sterically demanding
      bromine substituent. Subsequent Mannich-type N-acyliminium and radical
      cyclizations provide complete hexacyclic skeleton 33 of the aconitine alkaloids.
      Key endgame transformations include the installation of the C8-hydroxyl group via
      conjugate addition of water to a putative strained bridghead enone intermediate
      45 and one-carbon oxidative truncation of the C4 side chain to afford racemic
      neofinaconitine. Complete structural confirmation was provided by a concise relay
      synthesis of (+)-neofinaconitine and (+)-9-deoxylappaconitine from condelphine,
      with X-ray crystallographic analysis of the former clarifying the NMR spectral
      discrepancy between neofinaconitine and delphicrispuline, which were previously
      assigned identical structures. 

PMID- 24040960
TI  - First infection by all four non-severe acute respiratory syndrome human
      coronaviruses takes place during childhood.
AB  - BACKGROUND: Non-severe acute respiratory syndrome (non-SARS)-related human
      coronaviruses (HCoVs), including HCoV-229E, -HKU1, -NL63, and -OC43, have been
      detected in respiratory tract samples from children and adults. However, the
      natural prevalence of antibodies against these viruses in serum among population
      is unknown. METHODS: To measure antibodies to the spike (S) protein of the four
      common non-SARS HCoVs, recombinant S proteins of the four HCoVs were expressed
      and characterised in 293 T cell. An S-protein-based indirect immunofluorescence
      assay (IFA) was then developed to detect anti-S IgG and IgM for the four
      individual HCoVs and applied to serum samples from a general asymptomatic
      population (218 children and 576 adults) in Beijing. RESULTS: Of 794 blood
      samples tested, only 29 (3.65%) were negative for anti-S IgG. The seropositivity
      of the four anti-S IgG antibodies was >70% within the general population. The
      majority of seroconversions to four-HCoV positivity first occurred in children.
      Both S-IgG and S-IgM antibodies were detectable among children and increased with
      age, reaching a plateau at 6 years of age. However, no anti-S IgM was detected in
      healthy adults. CONCLUSION: Large proportions of children and adults in Beijing
      have evidence of anti-S IgG against four the HCoVs, and first infections by all
      four non-SARS HCoVs takes place during childhood.

PMID- 24040957
TI  - Role of NADPH oxidases in liver fibrosis.
AB  - SIGNIFICANCE: Hepatic fibrosis is the common pathophysiologic process resulting
      from chronic liver injury, characterized by the accumulation of an excessive
      extracellular matrix. Multiple lines of evidence indicate that oxidative stress
      plays a pivotal role in the pathogenesis of liver fibrosis. Nicotinamide adenine
      dinucleotide phosphate (NADPH) oxidase (NOX) is a multicomponent enzyme complex
      that generates reactive oxygen species (ROS) in response to a wide range of
      stimuli. In addition to phagocytic NOX2, there are six nonphagocytic NOX
      proteins. RECENT ADVANCES: In the liver, NOX is functionally expressed both in
      the phagocytic form and in the nonphagocytic form. NOX-derived ROS contributes to
      various kinds of liver disease caused by alcohol, hepatitis C virus, and toxic
      bile acids. Recent evidence indicates that both phagocytic NOX2 and nonphagocytic
      NOX isoforms, including NOX1 and NOX4, mediate distinct profibrogenic actions in
      hepatic stellate cells, the main fibrogenic cell type in the liver. The critical
      role of NOX in hepatic fibrogenesis provides a rationale to assess
      pharmacological NOX inhibitors that treat hepatic fibrosis in patients with
      chronic liver disease. CRITICAL ISSUES: Although there is compelling evidence
      indicating a crucial role for NOX-mediated ROS generation in hepatic
      fibrogenesis, little is known about the expression, subcellular localization,
      regulation, and redox signaling of NOX isoforms in specific cell types in the
      liver. Moreover, the exact mechanism of NOX-mediated fibrogenic signaling is
      still largely unknown. FUTURE DIRECTIONS: A better understanding through further
      research about NOX-mediated fibrogenic signaling may enable the development of
      novel anti-fibrotic therapy using NOX inhibition strategy. Antio

PMID- 24040961
TI  - A comprehensive analysis of oxidative stress in the ozone-induced lung
      inflammation mouse model.
AB  - Ozone is an oxidizing environmental pollutant that contributes significantly to
      respiratory health. Exposure to increased levels of ozone has been associated
      with worsening of symptoms of patients with asthma and COPD (chronic obstructive
      pulmonary disease). In the present study, we investigated the acute and chronic
      effects of ozone exposure-induced oxidative stress-related inflammation mechanics
      in mouse lung. In particular, we investigated the oxidative stress-induced
      effects on HDAC2 (histone deacetylase 2) modification and activation of the Nrf2
      (nuclear factor erythroid-related factor 2) and HIF-1alpha (hypoxia-inducible
      factor-1alpha) signalling pathways. Male C57BL/6 mice were exposed to ozone (3
      p.p.m.) for 3 h a day, twice a week for a period of 1, 3 or 6 weeks. Control mice
      were exposed to normal air. After the last exposure, mice were killed for BAL
      (bronchoalveolar lavage) fluid and lung tissue collection. BAL total cell counts
      were elevated at all of the time points studied. This was associated with
      increased levels of chemokines and cytokines in all ozone-exposed groups,
      indicating the presence of a persistent inflammatory environment in the lung.
      Increased inflammation and Lm (mean linear intercept) scores were observed in
      chronic exposed mice, indicating emphysematous changes were present in lungs of
      chronic exposed mice. The antioxidative stress response was active (indicated by
      increased Nrf2 activity and protein) after 1 week of ozone exposure, but this
      ability was lost after 3 and 6 weeks of ozone exposure. The transcription factor
      HIF-1alpha was elevated in 3- and 6-week ozone-exposed mice and this was
      associated with increased gene expression levels of several HIF-1alpha target
      genes including Hdac2 (histone deacetylase 2), Vegf (vascular endothelial growth
      factor), Keap1 (kelch-like ECH-associated protein 1) and Mif (macrophage
      migration inhibitory factor). HDAC2 protein was found to be phosphorylated and
      carbonylated in nuclear and cytoplasm fractions, respectively, and was associated
      with a decrease in DNA-binding activity and protein expression of HDAC2.
      Decreased HDAC2 activity, most likely a direct result of protein modification, in
      combination with the loss of the antioxidative stress response and activation of
      the HIF-1alpha pathway, contribute to the inflammatory response and emphysema
      observed in ozone-exposed mice.

PMID- 24040962
TI  - Ionic resistance and permselectivity tradeoffs in anion exchange membranes.
AB  - Salinity gradient energy technologies, such as reverse electrodialysis (RED) and
      capacitive mixing based on Donnan potential (Capmix CDP), could help address the
      global need for noncarbon-based energy. Anion exchange membranes (AEMs) are a key
      component in these systems, and improved AEMs are needed in order to optimize and
      extend salinity gradient energy technologies. We measured ionic resistance and
      permselectivity properties of quaternary ammonium-functionalized AEMs based on
      poly(sulfone) and poly(phenylene oxide) polymer backbones and developed structure
      property relationships between the transport properties and the water content and
      fixed charge concentration of the membranes. Ion transport and ion exclusion
      properties depend on the volume fraction of water in the polymer membrane, and
      the chemical nature of the polymer itself can influence fine-tuning of the
      transport properties to obtain membranes with other useful properties, such as
      chemical and dimensional stability. The ionic resistance of the AEMs considered
      in this study decreased by more than 3 orders of magnitude (i.e., from 3900 to
      1.6 Omega m) and the permselectivity decreased by 6% (i.e., from 0.91 to 0.85) as
      the volume fraction of water in the polymer was varied by a factor of 3.8 (i.e.,
      from 0.1 to 0.38). Water content was used to rationalize a tradeoff relationship
      between the permselectivity and ionic resistance of these AEMs whereby polymers
      with higher water content tend to have lower ionic resistance and lower
      permselectivity. The correlation of ion transport properties with water volume
      fraction and fixed charge concentration is discussed with emphasis on the
      importance of considering water volume fraction when interpreting ion transport
      data. 

PMID- 24040963
TI  - Competition among metal ions for protein binding sites: determinants of metal ion
      selectivity in proteins.

PMID- 24040964
TI  - Influence of inflammation on cardiovascular protective effects of cytochrome P450
      epoxygenase-derived epoxyeicosatrienoic acids.
AB  - In addition to their role as xenobiotic metabolizing enzymes, cytochrome P450
      (CYP) epoxygenases actively contribute to the metabolism of endogenous substances
      such as arachidonic acid. Epoxyeicosatrienoic acids (EETs) are epoxide derivative
      of arachidonic acid. CYP2C8/9 and CYP2J2 are the main epoxygenases expressed in
      human tissues including endothelial cells which are the chief sources of EET
      formation in human body. Once formed, EETs are primarily metabolized to their
      less biologically active metabolites, dihydroxyeicosatrienoic acids, by soluble
      epoxy hydrolase (sEH) enzyme. EETs possess a wide range of established protective
      effects on human cardiovascular system of which vasodilatory, angiogenic and anti
      inflammatory actions have been more extensively described. On the other hand,
      inflammation has shown to decrease the expression and activity of CYP enzyme,
      including epoxygenases. Given the fact that CYP epoxygenase-derive EETs exhibit
      potent cardiovascular protective effects, including anti-inflammation, and that
      inflammation suppress CYP activation and EET formation, it would make sense to
      speculate that under inflammatory conditions there exists an inflammation
      epoxygenase-EET-inflammation vicious cycle in which the inflammation-induced
      downregulation of CYP epoxygenases causes a decrease in the EET production.
      Insufficient EET synthesis would, in turn, lead to an ineffective EET-mediated
      anti-inflammatory effect, leading to an augmentation of systemic and regional
      inflammatory responses and further downregulation of CYP epoxygenase activity/EET
      production. This cycle, if any, might help to better understanding of
      pathophysiology of chronic cardiovascular diseases and also could be an emerging
      target for further pharmacological therapy of disorders in which increased
      inflammatory responses are known to occur.

PMID- 24040965
TI  - Synchrotron verification of TiO2 accumulation in cucumber fruit: a possible
      pathway of TiO2 nanoparticle transfer from soil into the food chain.
AB  - The transfer of nanoparticles (NPs) into the food chain through edible plants is
      of great concern. Cucumis sativus L. is a freshly consumed garden vegetable that
      could be in contact with NPs through biosolids and direct agrichemical
      application. In this research, cucumber plants were cultivated for 150 days in
      sandy loam soil treated with 0 to 750 mg TiO2 NPs kg(-1). Fruits were analyzed
      using synchrotron MU-XRF and MU-XANES, ICP-OES, and biochemical assays. Results
      showed that catalase in leaves increased (U mg(-1) protein) from 58.8 in control
      to 78.8 in 750 mg kg(-1) treatment; while ascorbate peroxidase decreased from
      21.9 to 14.1 in 500 mg kg(-1) treatment. Moreover, total chlorophyll content in
      leaves increased in the 750 mg kg(-1) treatment. Compared to control, FTIR
      spectra of fruit from TiO2 NP treated plants showed significant differences (p <=
      0.05) in band areas of amide, lignin, and carbohydrates, suggesting macromolecule
      modification of cucumber fruit. In addition, compared with control, plants
      treated with 500 mg kg(-1) had 35% more potassium and 34% more phosphorus. For
      the first time, MU-XRF and MU-XANES showed root-to-fruit translocation of TiO2 in
      cucumber without biotransformation. This suggests TiO2 could be introduced into
      the food chain with unknown consequences. 

PMID- 24040967
TI  - Analysis of a scenario for chaotic quantal slowing down of inspiration.
AB  - On exposure to opiates, preparations from rat brain stems have been observed to
      continue to produce regular expiratory signals, but to fail to produce some
      inspiratory signals. The numbers of expirations between two successive
      inspirations form an apparently random sequence. Here, we propose an explanation
      based on the qualitative theory of dynamical systems. A relatively simple
      scenario for the dynamics of interaction between the generators of expiratory and
      inspiratory signals produces pseudo-random behaviour of the type observed. 

PMID- 24040966
TI  - Role of conserved cis-regulatory elements in the post-transcriptional regulation
      of the human MECP2 gene involved in autism.
AB  - BACKGROUND: The MECP2 gene codes for methyl CpG binding protein 2 which regulates
      activities of other genes in the early development of the brain. Mutations in
      this gene have been associated with Rett syndrome, a form of autism. The purpose
      of this study was to investigate the role of evolutionarily conserved cis
      elements in regulating the post-transcriptional expression of the MECP2 gene and
      to explore their possible correlations with a mutation that is known to cause
      mental retardation. RESULTS: A bioinformatics approach was used to map
      evolutionarily conserved cis-regulatory elements in the transcribed regions of
      the human MECP2 gene and its mammalian orthologs. Cis-regulatory motifs including
      G-quadruplexes, microRNA target sites, and AU-rich elements have gained
      significant importance because of their role in key biological processes and as
      therapeutic targets. We discovered in the 5'-UTR (untranslated region) of MECP2
      mRNA a highly conserved G-quadruplex which overlapped a known deletion in Rett
      syndrome patients with decreased levels of MeCP2 protein. We believe that this 5'
      UTR G-quadruplex could be involved in regulating MECP2 translation. We mapped
      additional evolutionarily conserved G-quadruplexes, microRNA target sites, and AU
      rich elements in the key sections of both untranslated regions. Our studies
      suggest the regulation of translation, mRNA turnover, and development-related
      alternative MECP2 polyadenylation, putatively involving interactions of conserved
      cis-regulatory elements with their respective trans factors and complex
      interactions among the trans factors themselves. We discovered highly conserved G
      quadruplex motifs that were more prevalent near alternative splice sites as
      compared to the constitutive sites of the MECP2 gene. We also identified a pair
      of overlapping G-quadruplexes at an alternative 5' splice site that could
      potentially regulate alternative splicing in a negative as well as a positive way
      in the MECP2 pre-mRNAs. CONCLUSIONS: A Rett syndrome mutation with decreased
      protein expression was found to be associated with a conserved G-quadruplex. Our
      studies suggest that MECP2 post-transcriptional gene expression could be
      regulated by several evolutionarily conserved cis-elements like G-quadruplex
      motifs, microRNA target sites, and AU-rich elements. This phylogenetic analysis
      has provided some interesting and valuable insights into the regulation of the
      MECP2 gene involved in autism.

PMID- 24040968
TI  - Early platelet dysfunction in a rodent model of blunt traumatic brain injury
      reflects the acute traumatic coagulopathy found in humans.
AB  - Acute coagulopathy is a serious complication of traumatic brain injury (TBI) and
      is of uncertain etiology because of the complex nature of TBI. However, recent
      work has shown a correlation between mortality and abnormal hemostasis resulting
      from early platelet dysfunction. The aim of the current study was to develop and
      characterize a rodent model of TBI that mimics the human coagulopathic condition
      so that mechanisms of the early acute coagulopathy in TBI can be more readily
      assessed. Studies utilizing a highly reproducible constrained blunt-force brain
      injury in rats demonstrate a strong correlation with important postinjury
      pathological changes that are observed in human TBI patients, namely, diminished
      platelet responses to agonists, especially adenosine diphosphate (ADP), and
      subarachnoid bleeding. Additionally, administration of a direct thrombin
      inhibitor, preinjury, recovers platelet functionality to ADP stimulation,
      indicating a direct role for excess thrombin production in TBI-induced early
      platelet dysfunction.

PMID- 24040969
TI  - Ultrasonography of the spleen, liver, gallbladder, caudal vena cava and portal
      vein in healthy calves from birth to 104 days of age.
AB  - BACKGROUND: Many of the ultrasonographic abdominal findings of adult cattle
      probably also apply to calves. However, significant changes associated with
      ruminal growth and transition from a milk to a roughage diet occur in young
      calves during the first few months, and it can be expected that ultrasonographic
      features of organs adjacent to the rumen such as spleen and liver also undergo
      significant changes. These have not been investigated to date and therefore the
      goal of this study was to describe ultrasonographic findings of the spleen,
      liver, gallbladder, caudal vena cava and portal vein in six healthy calves from
      birth to 104 days of age. Standing calves were examined ultrasonographically six
      times at three-week intervals starting on the first or second day of life using a
      5.0-MHz transducer and techniques described previously. RESULTS: The spleen was
      imaged on the left at the 5th to 12th intercostal spaces. The dorsal and ventral
      visible limits ran from cranioventral to caudodorsal because of superimposition
      of the lungs. The size of the spleen was largest at the 7th and 8th intercostal
      spaces and the maximum thickness was measured at the 9th to 12th intercostal
      spaces. The liver was seen in all calves on the right and could be imaged at the
      5th to 12th intercostal spaces and the area caudal to the last rib. Similar to
      the spleen, the dorsal visible margin of the liver ran parallel to the ventral
      border of the lungs. The visible size of the liver was largest at the 8th to 11th
      intercostal spaces and the maximum thickness was measured at the 8th and 9th
      intercostal spaces. The parenchymal pattern consisted of numerous fine echoes
      homogeneously distributed over the entire organ. The gallbladder was most
      commonly seen at the 9th intercostal space and was circular, oval or pear-shaped
      on ultrasonograms. It extended beyond the ventral border of the liver depending
      on the amount of bile. The caudal vena cava was triangular in cross section but
      sometimes had a round or oval profile and was always seen in at least one
      intercostal space. The maximum circumference was measured at the 10th and 11th
      intercostal spaces. The portal vein was circular or oval in cross section and was
      characterised by stellate ramifications branching into the liver parenchyma. The
      portal vein could always be imaged at the 7th to 11th intercostal spaces and its
      mean diameter at the 9th to 11th intercostal spaces ranged from 1.2 cm to 1.8 cm.
      CONCLUSIONS: The ultrasonographic findings of the spleen, liver, gallbladder,
      caudal vena cava and portal vein in six healthy Holstein-Friesian calves from
      birth to 104 days of age serve as reference values for the examination of these
      anatomical structures in diseased calves.

PMID- 24040970
TI  - Perspectives of older adults on co-management of low back pain by doctors of
      chiropractic and family medicine physicians: a focus group study.
AB  - BACKGROUND: While older adults may seek care for low back pain (LBP) from both
      medical doctors (MDs) and doctors of chiropractic (DCs), co-management between
      these providers is uncommon. The purposes of this study were to describe the
      preferences of older adults for LBP co-management by MDs and DCs and to identify
      their concerns for receiving care under such a treatment model. METHODS: We
      conducted 10 focus groups with 48 older adults who received LBP care in the past
      year. Interviews explored participants' care seeking experiences, co-management
      preferences, and perceived challenges to successful implementation of a MD-DC co
      management model. We analyzed the qualitative data using thematic content
      analysis. RESULTS: Older adults considered LBP co-management by MDs and DCs a
      positive approach as the professions have complementary strengths. Participants
      wanted providers who worked in a co-management model to talk openly and honestly
      about LBP, offer clear and consistent recommendations about treatment, and
      provide individualized care. Facilitators of MD-DC co-management included
      collegial relationships between providers, arrangements between doctors to
      support interdisciplinary referral, computer systems that allowed exchange of
      health information between clinics, and practice settings where providers worked
      in one location. Perceived barriers to the co-management of LBP included the
      financial costs associated with receiving care from multiple providers
      concurrently, duplication of tests or imaging, scheduling and transportation
      problems, and potential side effects of medication and chiropractic care. A few
      participants expressed concern that some providers would not support a patient
      preferred co-managed care model. CONCLUSIONS: Older adults are interested in
      receiving LBP treatment co-managed by MDs and DCs. Older adults considered
      patient-centered communication, collegial interdisciplinary interactions between
      these providers, and administrative supports such as scheduling systems and
      health record sharing as key components for successful LBP co-management.

PMID- 24040971
TI  - Focus on pain in the blind.

PMID- 24040972
TI  - Hypersensitivity to pain in congenital blindness.
AB  - Vision is important for avoiding encounters with objects in the environment that
      may imperil physical integrity. We tested whether, in the absence of vision, a
      lower pain threshold would arise from an adaptive shift to other sensory
      channels. We therefore measured heat and cold pain thresholds and responses to
      suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal
      sighted participants. We also assessed detection thresholds for innocuous warmth
      and cold, and participants' attitude toward painful encounters in daily life. Our
      results show that, compared to sighted subjects, congenitally blind subjects have
      lower heat pain thresholds, rate suprathreshold heat pain stimuli as more
      painful, and have increased sensitivity for cold pain stimuli. Thresholds for
      nonpainful thermal stimulation did not differ between groups. The results of the
      pain questionnaires further indicated that blind subjects are more attentive to
      signals of external threats. These findings indicate that the absence of vision
      from birth induces a hypersensitivity to painful stimuli, lending new support to
      a model of sensory integration of vision and pain processing. 

PMID- 24040973
TI  - How do children with autism spectrum disorders express pain? A comparison with
      developmentally delayed and typically developing children.
AB  - There is a lack of knowledge about pain reactions in children with autism
      spectrum disorders (ASD), who have often been considered as insensitive to pain.
      The objective of this study was to describe the facial, behavioral and
      physiological reactions of children with ASD during venipuncture and to compare
      them to the reactions of children with an intellectual disability and nonimpaired
      control children. We also examined the relation between developmental age and
      pain reactions. The sample included 35 children with ASD, 32 children with an
      intellectual disability, and 36 nonimpaired children. The children were
      videotaped during venipuncture and their heart rate was recorded. Facial
      reactions were assessed using the Child Facial Coding System (CFCS) and
      behavioral reactions were scored using the Noncommunicating Children's Pain
      Checklist (NCCPC). A linear mixed-effects model showed that children's reactions
      increased between baseline and venipuncture and decreased between the end of
      venipuncture and the recovery period. There was no significant difference between
      groups regarding the amount of facial, behavioral and physiological reactions.
      However, behavioral reactions seemed to remain high in children with ASD after
      the end of the venipuncture, in contrast with children in the 2 other groups.
      Moreover, we observed a significant decrease in pain expression with age in
      nonimpaired children, but no such effect was found regarding children with ASD.
      The data reveal that children with ASD displayed a significant pain reaction in
      this situation and tend to recover more slowly after the painful experience.
      Improvement in pain assessment and management in this population is necessary. 

PMID- 24040974
TI  - Modulation of the human nociceptive flexion reflex by pleasant and unpleasant
      odors.
AB  - The nociceptive withdrawal reflex (NWR), a defensive response that allows
      withdrawal from a noxious stimulus, is a reliable index of spinal nociception in
      humans. It has been shown that various kinds of stimuli (emotional, visual,
      auditory) can modulate the transmission and perception of pain. The aim of the
      present study was to evaluate, by means of the NWR, the modulatory effect on the
      spinal circuitry of olfactory stimuli with different emotional valence. The
      magnitude of the NWR elicited by electrical stimulation of the sural nerve was
      measured while 18 subjects (9 women, 9 men) smelled pleasant, unpleasant, or
      neutral odors. The NWR was conditioned by odor probe with interstimulus intervals
      (ISIs) of 500 ms and 1,500 ms. The magnitude of NWR was significantly greater
      after the unpleasant odor probe (P <.001) and reduced following the pleasant odor
      probe (P<.001) at both ISIs. A significant effect of olfactory stimuli on
      subjective pain ratings were found at both ISIs for pleasant vs unpleasant odors
      (P<.000), and for both pleasant and unpleasant odors vs neutral and basal
      conditions (P<.000). No statistical differences in subjective pain ratings at
      different ISIs were found. Consistent with the notion that NWR magnitude and pain
      perception can be modulated by stimuli with different emotional valence, these
      results show that olfactory stimuli, too, can modulate spinal nociception in
      humans. 

PMID- 24040976
TI  - [Department of Gynecology and Obstetricin Faculty Hospital KV fifty years ago and
      today].

PMID- 24040977
TI  - [Diagnosis of minimal breast cancers].
AB  - DESIGN: This is a retrospective study evaluating the minimum detection cancers in
      the group of women mammographically examined in our department. The study covers
      the period from 1. 1. 2012 to 31. 12. 2012. Interestingly we introduced several
      interesting case studies. OBJECTIVE: 1. Confirmation upward trend in the number
      of minimal breast cancers, stage T1. 2. The need for multidisciplinary
      cooperation for quick minimal surgical intervention and effective cancer
      treatment. SETTING: Department of Radiology, Department of Gynecology and
      Obstetrics, Third Faculty of Medicine Charles University, Faculty Hospital KV,
      Prague. METHODS: The methodology is based on a retrospective evaluation of the
      number of participants, regardless of age, that come for examination the
      workplace Breast Radiologists in 2012. Of all the tests are then evaluated the
      number and types of histological proven cancer, focusing on cancer detection
      stage T1 and other solutions from surgery after cancer treatment. RESULTS: In
      2012 it was made in 6700 FNKV screening mammography, of this number, 45 were
      confirmed malignant tumors in asymptomatic women. In 2012 it was simultaneously
      performed 2276 diagnostic mammography in women with clinically palpable
      resistance, and malignant tumors was confirmed in 122 women. Overall,
      mammographically and ultrasonographically examined 10 146 women for the year
      2012. Of the 167 women with histologically confirmed malignant tumor. Brest
      carcinoma, stage T1, was diagnosed in 34% of patients and 66% of patients were
      malignant bearing greater than 10mm. The most common histological type of breast
      cancer in our department during the period from 1. 1. 2012 to 31. 12. 2012 was
      invasive ductal carcinoma (DIC) and in 82% of invasive lobular carcinoma (LIC)
      was diagnosed in 10%, mixed DIC and LIC in 4% and other cancers represented 4%.
      CONCLUSION: The diagnosis mode, core cut biopsy with histological conclusion,
      preoperative marking bearings in the presence of the surgeon, assessment
      resection, definitive histology, mammary team, cancer treatment, subsequent
      postoperative control at one workplace, is in terms of the patient not only
      effective, individualized and complex, but also cost effective.

PMID- 24040975
TI  - Brain white matter structural properties predict transition to chronic pain.
AB  - Neural mechanisms mediating the transition from acute to chronic pain remain
      largely unknown. In a longitudinal brain imaging study, we followed up patients
      with a single sub-acute back pain (SBP) episode for more than 1 year as their
      pain recovered (SBPr), or persisted (SBPp) representing a transition to chronic
      pain. We discovered brain white matter structural abnormalities (n=24 SBP
      patients; SBPp=12 and SBPr=12), as measured by diffusion tensor imaging (DTI), at
      entry into the study in SBPp in comparison to SBPr. These white matter fractional
      anisotropy (FA) differences accurately predicted pain persistence over the next
      year, which was validated in a second cohort (n=22 SBP patients; SBPp=11 and
      SBPr=11), and showed no further alterations over a 1-year period. Tractography
      analysis indicated that abnormal regional FA was linked to differential
      structural connectivity to medial vs lateral prefrontal cortex. Local FA was
      correlated with functional connectivity between medial prefrontal cortex and
      nucleus accumbens in SBPr. As we have earlier shown that the latter functional
      connectivity accurately predicts transition to chronic pain, we can conclude that
      brain structural differences, most likely existing before the back pain-inciting
      event and independent of the back pain, predispose subjects to pain
      chronification.

PMID- 24040978
TI  - [Laparoscopic treatment of borderline ovarian tumorsin fertile women].
AB  - OBJECTIVE: Evaluation of the benefits of laparoscopy and the fertility preserving
      approach in the borderline ovarian tumors. These tumors often occur in young
      women of childbearing age. The patient and the surgeon face a serious problem,
      especially for women who wish to maintain the possibility of pregnancy.
      Laparoscopy in these situations appear to be one of the preferred treatment
      methods. DESIGN: Retrospective study. SETTING: Third Faculty of Medicine, Charles
      University Prague, Gynecology and Obstetrics Department; P. J. Safarik
      University, L. Pasteur University Hospital, Kosice, Gynecology and Obstetrics
      Department; Hospital Ceske Budejovice. METHODS: Analysis of the data in 23 women
      who desired fertility and were operated laparoscopically for borderline ovarian
      tumors. We evaluated the extend of laparoscopic surgery, peri- and postoperative
      complications and final results of histopathological findings. RESULTS: Mean age
      of the patients was 30,4 years. All patients were completely staged during second
      laparoscopic operation. In 14 of 23 (60.9%) cases serous borderline tumor was
      identified, in 8 of 23 (34.8%) cases mucinous borderline tumor was identified and
      in one case Brenner tumor was diagnosed. Peritoneal implants were present in 5/14
      (35.7%) of serous tumors and in 3/8 (25%) of mucinous tumors. Involvement of
      contralateral ovary is also calculated. CONCLUSION: Borderline ovarian tumors
      occur in women who wish to maintain the possibility of pregnancy. For these
      patients, we choose based on their desire, conservative surgery. This treatment
      can be done by laparoscopy. Intraoperative ruptures of the tumor are more likely
      during lapaparoscopic procedures compared with laparotomy. In contrast,
      laparoscopy provides, besides well-known advantages, better optical evaluation of
      the abdominal cavity, including the detection of superficial peritoneal implants.
      For the objective evaluation of the laparoscopic approach in patients with
      fertility desire, further prospective comparative study are needed.

PMID- 24040979
TI  - [Cooperation between mammologist and radiodiagnostic in the management of mammary
      leasions in the University Hospital Kralovske Vinohrady].
AB  - Epidemiological datas describing up to date status of diagnostics and oncological
      parameters (incidence, mortality, prevalence, total number of pacients with
      breast cancer) are given in the article. Further changes are comented in this
      field after start of mammografic screening programme in our country in the year
      2002. Authors evaluated possibilities of clinical diagnostics performed by
      mammologist in his ambulance and possibilities and types of invasive and
      noninvasive (immaging) diagnostic methods performed by radiodiagnostic according
      mammologist indication. Management of benign and malignant leasions detected and
      treated in the mammological centre of the University Hospital Kralovske Vinohrady
      are mentioned.

PMID- 24040980
TI  - [Retrospective analysis of effectiveness of transvaginal ultrasound in the
      detection of ectopic pregnancy].
AB  - OBJECTIVE: To evaluate the effectiveness of transvaginal ultrasonographic (US)
      scan in own group of patients. DESIGN: Retrospective analysis. SETTING:
      Department of Gynaecology and Obstetrics, 3rd Faculty of Medicine, Charles
      University and Faculty Hospital Kralovske Vinohrady, Prague. METHODS: We
      retrospectively evaluated the history, laboratory and ultrasound findings in a
      group of 115 patients, that have undergone a surgical procedure due to a positive
      diagnose or suspicion of ectopic pregnancy (EP). In all cases the diagnose of
      ectopic pregnancy was histologically confirmed. RESULTS: 67% of our patients were
      nulliparous, 10% of patients had a positive personal history of previous ectopic
      pregnancy, only 5% of pacients had a record of pelvic inflammatory disease in the
      past. Histological examination confirmed 96.5% (111/115) tubal, 1.7% (2/115)
      interstitial, 0.9% (1/115) ovarian and 0.9% (1/115) cervical ectopic pregnancy.
      Our transvaginal ultrasonography (TVUS) scan was successful in 76.5% (88/115). A
      pathological adnexal mass was visualised in 67% (77/115) cases. A negative
      ultrasound finding was observed in 23.5% (27/115) cases. CONCLUSION: The US
      detection of ectopic pregnancy by a single TVUS examination was successful in
      76.5% (88/115) cases. Early detection of ectopic pregnancy by TVUS decreases the
      risk of rupture of different types of EP, decreases the rate of surgical
      interventions and also promotes conservative management of ectopic pregnancies.

PMID- 24040981
TI  - [The importance of circulating tumor cells in the diagnostic and therapeutic
      process in ovarian cancer].
AB  - OBJECTIVE: Our goal was to summarize clinical studies which used CTC/CSCs for
      prognosis in patients with ovarian cancer. TYPE OF STUDY: Review article.
      SETTING: Department of Gynecology and Obstetrics, 3rd Faculty of Medicine,
      Charles University, Faculty Hospital Kralovske Vinohrady, Prague. MATERIAL AND
      METHODS: This paper reviews various methods of CTCs detection as well as the
      biology and molecular characterisation of CTCs/CSCs. CONCLUSION: Determination of
      CTC (circulating tumor cells) / CSCS (cancer stem cells) has great potential in
      the diagnosis, prognosis, monitoring of disease, therapeutic effect and the risk
      of relapse in ovarian cancer for other malignancies. The presence of CTCs / CSCS
      in the blood seems to be a decisive factor in the initiation of metastatic
      process. The results of these studies show a clear link CTC negativity with an
      extension length of progression-free interval (PFI) and overall survival in
      patients with ovarian cancer.

PMID- 24040982
TI  - [Position of targeted therapy in ovarian cancer management].
AB  - Ovarian cancer in Czech Republic takes first place in mortality among
      gynecological malignant tumours. In most cases it is diagnosed in advanced
      stages. Initial treatment is based on combination of radical surgery and adjuvant
      chemotherapy. In more than two thirds of cases ovarian cancer relapses sooner or
      later, very often without a chance to cure the patient. Unsatisfying result of
      standard treatment is reason of looking for more effective procedures. Targeted
      therapy is subject of research in last years. Positive effect of bevacizumab has
      been proved. Through inhibition of angiogenesis it leads to prolonging of
      interval to cancer progression.

PMID- 24040983
TI  - [Vulvar melanoma].
AB  - OBJECTIVE: Malignant melanoma of the vulva is the second commonest vulval
      malignancy. This article will focus on three cases of vulvar melanoma which have
      been solved surgically with wide excision, sentinel lymph node biopsy and radical
      lymphadenectomy. DESIGN: Case report. SETTING: Department of Dermatovenerology
      3rd Faculty of Medicine, Charles University, Faculty Hospital Kralovske
      Vinohrady, Prague. METHODS: Biopsy of the lesion creates a reliable diagnostic
      procedure. More frequently digital dermoscopy is used for the precise primary
      diagnostics and follow-up of pigment vulvar lesions. RESULTS: Vulvar melanoma has
      been variously estimated to account for between 3.6 and 10% of malignant vulvar
      neoplasms. An epidemiologic study revealed ratio of vulvar to skin melanoma 1:71.
      CONCLUSION: New diagnostic methods such as digital dermoscopy or sentinel node
      biopsy bringing ever greater progress in precise diagnosis of patients with
      vulvar melanoma.

PMID- 24040984
TI  - [The injury of bladder without penetrate during the TVT surgery for stress
      incontinence].
AB  - OBJECTIVE: The aim of this article is alert to possibile of non-penetrating
      injury of bladder and risk of extraperitoneal bleeding during the TVT surgery
      when the tape is inserted by retropubic path. This type of injury can't be find
      by cystoscopy and there can be a serious blood loss in to the interstitial space.
      According this fact, there is a great importance of this injury and there is an
      urgent need to prompt reaction on this situation. In this way, we do prevent
      serious risk of health damage. DESIGN: Case report. SETTING: Department of
      Obstetrics and Gynaecology, 3rd Faculty of Medicine, Charles University, Faculty
      Hospital Kralovske Vinohrady, Prague. METHODS: The different authors presents
      various percentage of complications in the case of TVT surgery. The differences
      follow from size of patient's group, type of surgical procedure, type of the tape
      and the way of tape insertion. Nevertheless, differences between these results
      are statistically nonsignificant. CONCLUSIONS: The operation's complications and
      early after operation's complications can arise in the course of any surgery and
      iatrogenic complications also belong to this group. Minimally invasive surgery is
      certainly make not an exception. The most often signs of these complications are
      abdominal pain, presence of blood in urine, anemia, malfunction of bladder and
      possible breakdown of intestinal activity. If the conservative methods failed, we
      have to perform operating inspection. The cooperation with surgeon or urologist
      is certainly needed.

PMID- 24040985
TI  - [Antibiotical prophylaxy in gynecology].
AB  - Gynecological surgery is considered to be clear with possible contamination by
      gram-positive cocci from the skin, gram-negatives from the perineum or groins or
      polymicrobial biocenosis from vagina, depending on the surgical approach.
      Antibiotical prophylaxy enforces the natural mechanisms of immunity and helps to
      exclude present infection. There were presented many studies comparing useful
      effect of prophylaxis in gynecological surgery. The benefits of antibiotical
      prophylaxy before IUD insertion, before the cervical surgery and before
      hysteroscopies were not verified. On the other hand the prophylaxy of vaginal
      surgery including vaginal hysterectomy decreases the number of postoperative
      febrile complications. The positive influence of prophylaxis before the simple
      laparoscopy and laparoscopy without bowel injury or the opening of the vagina was
      not evidently verified. In abdominal hysterectomy the antibiotical prophylaxy
      decreases the incidence of postoperative complications significantly. The
      administration of 2 g of cefazolin can be recommended. In procedures taking more
      than 3 hours the repeated administration of cefazolin is suitable. New
      urogynecological procedures, using mesh implants, were not sufficiently evaluated
      as for postoperative infections and the posible antibiotical effect. The presence
      of implant in possibly non sterile area should be considered as high risc of
      postoperative complications.

PMID- 24040986
TI  - [Umbilical cord blood soluble Toll-like receptor 2 in pregnancies complicated by
      preterm premature rupture of membranes].
AB  - OBJECTIVE: To determine whether umbilical cord blood concentrations of soluble
      Toll-like receptor (sTLR2) is of value in the diagnosis of histological
      chorioamnionitis (HCA) and funisitis in pregnancies complicated by preterm
      premature rupture of membranes. DESIGN: Retrospective study. SETTING: Charles
      University in Prague, Faculty of Medicine and University Hospital, Hradec
      Kralove, Department of Clinical Immunology and Allergy, Department of Obstetric
      and Gynecology. METHODS: Eighty six women with PPROM between gestation ages 24
      and 36 weeks were included in the study. The samples of the umbilical cord blood
      were taken from the clamped umbilical cord immediately after delivery of the
      newborn. The placenta, fetal membranes and umbilical cord were evaluated for the
      presence of inflammatory changes. The concentrations of sTLR2 in the umbilical
      cord blood were measured by ELISA method. RESULTS: Women with HCA did not have
      different umbilical cord blood sTLR2 levels than women without HCA (with HCA:
      median 7.6 ng/mL, interquartile range [IQR] 5.1 - 12.3 vs. without HCA: median
      8.0 ng/mL, IQR 6.0 - 9.4; p = 0.79). No differences between women with and
      without funisitis were found (median 7.2 ng/mL, IQR 5.5 - 22.3 vs. without
      funisitis: median 7.9 ng/mL, IQR 5.2 - 10.5; p = 0.31). CONCLUSION: Umbilical
      cord blood sTRL2 levels are not affected by the presence of either HCA or
      funisitis in pregnancies complicated with PPROM.

PMID- 24040987
TI  - [Rapid detection of the most common chromosomal aneuploidies in the second
      trimester amniotic fluid using QF-PCR].
AB  - OBJECTIVE: To introduce QF-PCR method for detection of the most common
      chromosomal (trisomy 21, 18 and 13) and gonosomal aneuploidies at our department
      in the second-trimester amniotic fluid. To test the hypothesis of chromosomal
      aneuploidies detection using STR markers of Aneufast(r) kit via analysing free
      fetal DNA (ffDNA) isolated from plasma of pregnant women with confirmed trisomy
      21 in fetus. DESIGN: A prospective clinical study. SETTING: Department of
      Obstetrics and Gynecology, Jessenius Faculty of Medicine and University Hospital
      in Martin, Slovak Republic. METHODS: The samples of amniotic fluid were obtained
      from 67 women (twin pregnancy in 3 cases) in the 2nd trimester (15th to 22nd
      gestational week (g.w.)). Samples were examined using multiplex QF-PCR via
      Aneufast kit. In the case of positivity for trisomy 21, they were re-examined
      using Devyser Resolution 21 kit. All samples were parallelly evaluated by
      cytogenetic karyotyping. We also analyzed ffDNA from the plasma of 3 high-risk
      women using Aneufast kit. The plasma samples were obtained in the 2nd
      trimester(17th to 21st g.w.). Qiaamp DSP Virus kit was used for ffDNA isolation.
      Trisomy 21 of 3 fetuses was confirmed by karyotyping after 2nd trimester
      amniocentesis. RESULTS: In the cohort of 70 samples, 7 pathological results (six
      trisomies 21 and one trisomy 18) were obtained. There was 100% concordance with
      cytogenetic karyotype in all samples examined by QF-PCR. The amplification of
      tracked chromosome 21 fragments was not evaluable in the case of ffDNA analysis.
      CONCLUSION: QF-PCR was approved as reliable, rapid, quite simple and financially
      bearable method of prenatal diagnostics. Despite the fact of good availability
      and work implementation of Aneufast(r) kit, results of ffDNA analysis are
      insufficient. We did not obtain interpretable results after ffDNA analysis from
      maternal plasma in trisomy 21 fetuses.

PMID- 24040988
TI  - [Peripartal life-threating haemorrhage - intensive care and haematological
      treatment].
AB  - Peripartal life-threating bleeding is serious and frequent complication comming
      during the labor. Diagnosis is based on assesment of blood loss and the reason of
      bleeding. Obstetrical and surgical treatment including invasive radiological
      methods combining with resuscitation care based on support organ functions and
      energic susbstitution coagulation components is essential. The aim is to rescue
      the life of women and to preserv her reproductive ability.

PMID- 24040989
TI  - [Nocturnal polyuria, treatment with desmopressin].
AB  - Nonpharmacologic and especially pharmacologic treatment options are available for
      nocturnal polyuria. Desmopressin represents the basis of pharmacologic treatment.
      Desmopressin acetate is a synthetic analogue of arginine vasopressin with high
      affinity to V2 receptors with antidiuretic effect. It is the only medicament
      currently registered for antidiuretic treatment. Desmopressin has not any
      relevant affinity to V1 receptors, and therefore there is no hypertensive effect
      in contrary to natural vasopressin. Desmopressin use before a bedtime leads to
      reduced production of urine during a sleep, therefore time between desires to
      void is prolonged and number of nocturia is reduced. Clinical effect, in a
      meaning of reduced urine production and increased osmolality of urine, lasts
      approximately 8-12 hours. In the treatment of nocturnal polyuria desmopressin is
      used orally one hour before a bedtime. It is essential to titrate an ideal dose,
      the initial dose is 60 ug of MELT formula (fast melting oral formulation) and it
      can be increased according to the clinical effect up to the maximal recommended
      daily dose 240 ug. Patients treated with desmopressin should cut down a fluid
      intake 1 hour before and 8 hours after the use of desmopressin. Total number of
      adverse events connected withdesmopressin treatment in clinical studies was
      higher compared to placebo but the side effects were mostly mild. The most common
      adverse events were headaches, nausea, diarrhoea, abdominal pain, dry mouth and
      hyponatremia both in the short-term and long-term clinical trials. Hyponatremia
      was observed mainly in patients over 65 year of age. Therefore treatment with
      desmopressin should not be commended in patients over 65 year of age without
      close monitoring of the natrium level in serum and all patients should be
      informed about the first symptoms of hyponatremia - headache, nausea and
      insomnia. According to Evidence Based Medicine, the level of evidence for
      treatment of nocturnal polyuria with desmopressin is 1b and the grade of
      recommendation for treatment is A. KEYWORDS: nocturnal polyuria - treatment -
      desmopressin.

PMID- 24040990
TI  - [Current issues of assisted reproduction in the Czech Republic].
AB  - INTRODUCTION: Participants of the lunch table discussion held during the 22nd
      symposium of assisted reproduction in Brno discussed some current topics of
      assisted reproduction. DISCUSSED TOPICS: More than 150 participants at round
      tables discussed 10 topics: 1. IVF in native AR cycle,2. observation of the
      embryo development dynamics, 3. evaluation and support of endometrial
      receptivity,4. increased number of elective single embryo transfers (eSET), 5.
      transport of gametes and embryos in the Czech Republic and between the Czech
      Republic and abroad, 6. National registry of assisted reproduction,7. new view on
      sperm pathology, 8. problems with the SAR membership records, 9. surogacy
      motherhood and 10. preimplantation genetic diagnosis and preimplantation genetic
      screening. CONCLUSIONS: All findings were presented in the afternoon session.
      Some of the topics brought concrete results. Some topics could not be clearly
      concluded and will be the subject of further discussions. A brief summary of
      those discussion conclusions presents this paper.

PMID- 24040991
TI  - [Theoretic and practical content of the clinical embryology].
AB  - Clinical embryology is in whole Europe respected health care specialization. The
      specialists in this field are certified by the European Society of Human
      Reproduction and Embryology (ESHRE). In the Czech Republic the specialization has
      been formally established by the Government Order No 31/ 2010 after 30 years
      unformal existence. Concurrently with the wide development of new techniques in
      assisted reproduction, there is necessary to define the content of clinical
      embryology as a health care, scientific and educational discipline. The
      definition authorized by the Committee of Association of Reproductive Embryology
      (ARE) is given in this article..

PMID- 24040993
TI  - HOLZ rings in EBSD patterns of the UFeB4 compound: association with a random
      distribution of planar defects.
AB  - The UFeB4 phase present in different alloys of the B-Fe-U system was studied by
      powder X-ray diffraction (PXRD) and scanning electron microscopy complemented
      with energy-dispersive spectroscopy and electron backscattered diffraction
      (EBSD). The PXRD data showed that the ternary compound crystallized adopting
      essentially the YCrB4-type structure. However, microstructural observations
      revealed that under high undercooling conditions the UFeB4 phase exhibits a
      random distribution of defects parallel to, which are consistently associated
      with intense higher-order Laue zone rings in EBSD patterns. Indexation of the
      EBSD patterns showed that the defective structure is compatible with an
      intergrowth of YCrB4- and ThMoB4-type layers according to the
      (010)(YCrB4)//(110)(ThMoB4) and [001]YCrB4//[001](ThMoB4) orientation relation
      previously reported for an analogous compound. Magnetic studies indicated that
      the annealed UFeB4 compound has a paramagnetic behavior in the 2-300 K
      temperature range.

PMID- 24040992
TI  - An efficient light-driven P450 BM3 biocatalyst.
AB  - P450s are heme thiolate enzymes that catalyze the regio- and stereoselective
      functionalization of unactivated C-H bonds using molecular dioxygen and two
      electrons delivered by the reductase. We have developed hybrid P450 BM3 heme
      domains containing a covalently attached Ru(II) photosensitizer in order to
      circumvent the dependency on the reductase and perform P450 reactions upon
      visible light irradiation. A highly active hybrid enzyme with improved stability
      and a modified Ru(II) photosensitizer is able to catalyze the light-driven
      hydroxylation of lauric acid with total turnover numbers of 935 and initial
      reaction rate of 125 mol product/(mol enzyme/min). 

PMID- 24040994
TI  - Evaluation of the carcinogenicity of inorganic arsenic.
AB  - Inorganic arsenic (iAs) at high exposures is a human carcinogen, affecting mainly
      the urinary bladder, lung and skin. We present an assessment of the mode of
      action (MOA) of iAs's carcinogenicity based on the United States Environmental
      Protection Agency/International Programme on Chemical Safety (USEPA/IPCS)
      framework, focusing primarily on bladder cancer. Evidence is presented for a MOA
      involving formation of reactive trivalent metabolites interacting with critical
      cellular sulfhydryl groups, leading to cytotoxicity and regenerative cell
      proliferation. Metabolism, kinetics, cell transport, and reaction with specific
      proteins play a critical role in producing the effects at the cellular level,
      regardless of cell type, whether urothelium, lung epithelium or epidermis. The
      cytotoxicity induced by iAs results in non-cancer toxicities, and the
      regenerative cell proliferation enhances development of epithelial cancers. In
      other tissues, such as vascular endothelium, different toxicities develop, not
      cancer. Evidence supporting this MOA comes from in vitro investigations on animal
      and human cells, from animal models, and from epidemiological studies. This MOA
      implies a non-linear, threshold dose-response relationship for both non-cancer
      and cancer end points. The no effect levels in animal models (approximately 1 ppm
      of water or diet) and in vitro (>0.1 uM trivalent arsenicals) are strikingly
      consistent. Cancer effects of iAs in humans generally are not observed below
      exposures of 100-150 ppb in drinking water: below these exposures, human urine
      concentrations of trivalent metabolites are generally below 0.1 uM, a
      concentration not associated with bladder cell cytotoxicity in in vitro or animal
      models. Environmental exposures to iAs in most of the United States do not
      approach this threshold.

PMID- 24040995
TI  - A survey of frameworks for best practices in weight-of-evidence analyses.
AB  - The National Academy of Sciences (NAS) Review of the Environmental Protection
      Agency's Draft IRIS Assessment of Formaldehyde proposed a "roadmap" for reform
      and improvement of the Agency's risk assessment process. Specifically, it called
      for development of a transparent and defensible methodology for weight-of
      evidence (WoE) assessments. To facilitate development of an improved process, we
      developed a white paper that reviewed approximately 50 existing WoE frameworks,
      seeking insights from their variations and nominating best practices for WoE
      analyses of causation of chemical risks. Four phases of WoE analysis were
      identified and evaluated in each framework: (1) defining the causal question and
      developing criteria for study selection, (2) developing and applying criteria for
      review of individual studies, (3) evaluating and integrating evidence and (4)
      drawing conclusions based on inferences. We circulated the draft white paper to
      stakeholders and then held a facilitated, multi-disciplinary invited stakeholder
      workshop to broaden and deepen the discussion on methods, rationales, utility and
      limitations among the surveyed WoE frameworks. The workshop developed
      recommendations for improving the conduct of WoE evaluations. Based on the
      analysis of the 50 frameworks and discussions at the workshop, best practices in
      conducting WoE analyses were identified for each of the four phases. Many of
      these best practices noted from the analysis and workshop could be implemented
      immediately, while others may require additional refinement as part of the
      ongoing discussions for improving the scientific basis of chemical risk
      assessments.

PMID- 24040996
TI  - A statistical reevaluation of the data used in the Lanphear et al. ( 2005 )
      pooled-analysis that related low levels of blood lead to intellectual deficits in
      children.
AB  - A pooled-analysis by Lanphear et al. (2005) of seven cohort studies of the
      association between blood lead (BPb) concentrations in children and measures of
      their intelligence concluded that "environmental lead exposure in children who
      have maximal blood lead levels <7.5 MUg/dL is associated with intellectual
      deficits." This study has played a prominent role in shaping the public
      understanding of the effects upon children's IQ of low BPb exposures (e.g., BPb
      <= 10 MUg/dL). Here we present a reanalysis of the data used by Lanphear et al.
      to evaluate the robustness of their conclusions. Our analysis differed from that
      of Lanphear et al. primarily in how we controlled for non-lead variables
      (allowing a number of them to be site-specific), how we defined summary measures
      of BPb exposure, and in how we decided which BPb measures and transformations
      best modeled the data. We also reproduced the Lanphear et al. analysis. Although
      we found some small errors and questionable decisions by Lanphear et al. that,
      taken alone, could cause doubt in their conclusions, our reanalysis tended to
      support their conclusions. We concluded that there was statistical evidence that
      the exposure-response is non-linear over the full range of BPb evaluated in these
      studies, which implies that, for a given increase in blood lead, the associated
      IQ decrement is greater at lower BPb levels. However at BPb below 10 ug/dL, the
      exposure-response is adequately modeled as linear. We also found statistical
      evidence for an association with IQ among children who had maximal measured BPb
      levels <=7 MUg/dL, and concurrent BPb levels as low as <=5 MUg/dL.

PMID- 24040998
TI  - Meta-analysis: a tool for clinical and experimental research in psychiatry.
AB  - The meta-analysis study is a type of systematic review with strong scientific
      rigor; it has a number of characteristics that makes it a very useful tool.
      However, performing and reading meta-analysis could be a challenge-the meta
      analysis overcomes the limitation of small sample sizes or rare outcomes by
      pooling results from individual studies in order to generate a single and better
      estimate. It also increases statistical power and allows the evaluation of
      discrepancies among the results of different studies. In this paper, we will
      present examples to illustrate how psychiatrists can utilize a meta-analysis in
      clinical and experimental research.

PMID- 24041000
TI  - Intellect and cognitive performance in the Lothian Birth Cohort 1936.
AB  - Investment personality traits are thought to positively affect cognitive
      performance in old age, even after controlling for prior cognitive ability. In
      the Lothian Birth Cohort 1936 (N = 1,091), a cross-lagged model tested for
      reciprocal effects of the investment trait Intellect on verbal fluency, an
      indicator of crystallized intelligence, at age 70 and 73 years, while adjusting
      for general IQ at age 11 and 70 years. Intellect at age 70 was weakly associated
      with contemporaneous verbal fluency but had no significant effects on fluency at
      age 73. Conversely, verbal fluency at age 70 was significantly, positively
      related to Intellect at age 73. The results suggest that better verbal fluency
      precedes intellectual investment in old age rather than the other way around.

PMID- 24040999
TI  - Complementary cognitive capabilities, economic decision making, and aging.
AB  - Fluid intelligence decreases with age, yet evidence about age declines in
      decision-making quality is mixed: Depending on the study, older adults make
      worse, equally good, or even better decisions than younger adults. We propose a
      potential explanation for this puzzle, namely that age differences in decision
      performance result from the interplay between two sets of cognitive capabilities
      that impact decision making, one in which older adults fare worse (i.e., fluid
      intelligence) and one in which they fare better (i.e., crystallized
      intelligence). Specifically, we hypothesized that older adults' higher levels of
      crystallized intelligence can provide an alternate pathway to good decisions when
      the fluid intelligence pathway declines. The performance of older adults relative
      to younger adults therefore depends on the relative importance of each type of
      intelligence for the decision at hand. We tested this complementary capabilities
      hypothesis in a broad sample of younger and older adults, collecting a battery of
      standard cognitive measures and measures of economically important decision
      making "traits"--including temporal discounting, loss aversion, financial
      literacy, and debt literacy. We found that older participants performed as well
      as or better than younger participants on these four decision-making measures.
      Structural equation modeling verified our hypothesis: Older participants' greater
      crystallized intelligence offset their lower levels of fluid intelligence for
      temporal discounting, financial literacy, and debt literacy, but not for loss
      aversion. These results have important implications for public policy and for the
      design of effective decision environments for older adults.

PMID- 24040997
TI  - Redox-relevant aspects of the extracellular matrix and its cellular contacts via
      integrins.
AB  - SIGNIFICANCE: The extracellular matrix (ECM) fulfills essential functions in
      multicellular organisms. It provides the mechanical scaffold and environmental
      cues to cells. Upon cell attachment, the ECM signals into the cells. In this
      process, reactive oxygen species (ROS) are physiologically used as signalizing
      molecules. RECENT ADVANCES: ECM attachment influences the ROS-production of
      cells. In turn, ROS affect the production, assembly and turnover of the ECM
      during wound healing and matrix remodeling. Pathological changes of ROS levels
      lead to excess ECM production and increased tissue contraction in fibrotic
      disorders and desmoplastic tumors. Integrins are cell adhesion molecules which
      mediate cell adhesion and force transmission between cells and the ECM. They have
      been identified as a target of redox-regulation by ROS. Cysteine-based redox
      modifications, together with structural data, highlighted particular regions
      within integrin heterodimers that may be subject to redox-dependent
      conformational changes along with an alteration of integrin binding activity.
      CRITICAL ISSUES: In a molecular model, a long-range disulfide-bridge within the
      integrin beta-subunit and disulfide bridges within the genu and calf-2 domains of
      the integrin alpha-subunit may control the transition between the bent/inactive
      and upright/active conformation of the integrin ectodomain. These thiol-based
      intramolecular cross-linkages occur in the stalk domain of both integrin
      subunits, whereas the ligand-binding integrin headpiece is apparently unaffected
      by redox-regulation. FUTURE DIRECTIONS: Redox-regulation of the integrin
      activation state may explain the effect of ROS in physiological processes. A
      deeper understanding of the underlying mechanism may open new prospects for the
      treatment of fibrotic disorders.

PMID- 24041002
TI  - Effects of personality on the transition into caregiving.
AB  - Recent research has emphasized the critical role of personality in the caregiving
      situation, but not much is known about how individual differences shape the
      transitions into and out of caregiving. Based on longitudinal data from the
      German Socio-Economic Panel (SOEP, N= 14,495), we explored how personality is
      associated with adopting and maintaining the caregiving role. The results
      revealed that individuals with less emotional stability were more likely to take
      over the responsibility to provide care. Moreover, care-related personality
      change was affected by sex and age. In detail, female care entrants were more
      burdened than their male counterparts, and younger caregivers seemed to adapt
      better to the caregiving role than older ones. The findings point to the
      interplay of personality and sociostructural conditions in the caregiving role
      over time.

PMID- 24041001
TI  - Mind-wandering and falls risk in older adults.
AB  - Although mind-wandering is common, engaging in task-irrelevant thoughts can have
      negative functional consequences. We examined whether mind-wandering frequency
      may be related to falls-a major health-care problem. Seniors completed a
      sustained attention task and self-reported their current attentional states.
      Monthly falls reports were collected over 12 months. Falls were associated with
      an increased frequency of mind-wandering. In addition, poorer performance on the
      sustained attention task was associated with more falls over 12 months. Given
      that fallers are known to have impaired executive cognitive functioning, our
      results are consistent with the current theory that poor attentional control may
      contribute to the occurrence of mind-wandering.

PMID- 24041003
TI  - Context-updating processes facilitate response reprogramming in younger but not
      older adults.
AB  - The current study used concurrent acquisition of motion capture and event-related
      potential (ERP) data to test the prediction that response reprogramming relies on
      context-updating processes, and that age differences in conflicting-response
      performance are related to context-updating deficits in the elderly. Participants
      performed a motor sequencing task that included prepotent pairs of key presses,
      and conflicting pairs that started with the same first key press of the prepotent
      pair, but ended in an unexpected alternate response. ERP analyses were used to
      measure the P3b component as an electrophysiological correlate of context
      updating. The results revealed an age-related reduction in the ability to
      reprogram a response as younger, but not older, adults exhibited a negative
      correlation between planning and execution time for conflicting responses, such
      that shortened execution time led to better performance by the younger group.
      Both age groups demonstrated a large P3b component following conflicting, but not
      prepotent stimuli. The peak of this P3b was delayed, and its amplitude reduced in
      the older, compared with younger, adults. Noteworthy was that conflicting
      responses with faster execution time were associated with a larger P3b component
      than responses with slower execution time in younger, but not older, adults,
      suggesting that better context updating led to more efficient response
      reprogramming. These findings are novel in showing that context updating is
      associated with adjustments in response execution, and that older adults were
      less able to use these context-updating processes to support successful movement
      reprogramming.

PMID- 24041004
TI  - Adult age differences, response management, and cue focality in event-based
      prospective memory: a meta-analysis on the role of task order specificity.
AB  - The present meta-analysis investigated whether event-based prospective memory
      (PM) age effects differ by task order specificity. In specified PM tasks, the
      order of the ongoing and the PM task response is predetermined, which imposes
      demands on cognitive control to navigate the possible response options. In
      contrast, unspecified PM tasks do not require responding in a particular order.
      Based on 57 studies and more than 5,500 younger and older adults, results showed
      larger PM age effects in specified compared with unspecified PM tasks.
      Additionally, the effect of task focality on age differences was replicated.
      Results suggest that both pre- and postretrieval processes independently affect
      PM age effects.

PMID- 24041005
TI  - Emotion recognition deficits exist in mild cognitive impairment, but only in the
      amnestic subtype.
AB  - Emotion recognition is impaired in dementia and there is some initial evidence to
      suggest that milder deficits may be present in Mild Cognitive Impairment (MCI)
      patients, an "at risk" population for transition to dementia. In this study, we
      investigated the emotion recognition profile of MCI subgroups. Results show
      emotion recognition deficits exist for the amnestic subtype with impairment in
      multiple domains, with an emotion-specific deficit for anger recognition.
      Impaired emotion recognition in aMCI was independent of patient mood and
      cognitive deficits. The study is the first to examine the nonamnestic subtype. No
      emotion recognition deficits were found. This finding is surprising given the
      association between the nonamnestic subtype and frontal systems dysfunction.
      Impaired emotion recognition could be related to the selective pathophysiology in
      neural pathways, particularly the temporal lobe and connected limbic and
      prefrontal regions, implicated in both aMCI and emotion processing. These
      findings may have implications for early diagnosis, prognosis, and clinical
      management.

PMID- 24041007
TI  - Controllable interfacial adhesion applied to transfer light and fragile objects
      by using gecko inspired mushroom-shaped pillar surface.
AB  - Gecko-inspired surfaces are smart dry adhesive surfaces that have attracted much
      attention because of their wide range of potential applications. However, strong
      frictional force, rather than adhesive force, is frequently targeted in most of
      research in this area. In this study, the interfacial adhesive and frictional
      properties of a gecko-inspired mushroom-shaped polyurethane pillar array surface
      have been systematically characterized to design and control the interfacial
      adhesion of the surface by considering the nanoscale interfacial adhesion, the
      microscale structural compliance and deformation, and the macro-scale actuation.
      Matching the movement of the leg springs and the interfacial adhesive
      characteristics between the pillar array surfaces and substrates, a three-legged
      clamp prototype has been designed and fabricated to successfully pick up and
      release light and fragile objects with a smooth upper surface, such as a silicon
      wafer. These results provide a new insight into not only the theoretical
      understanding of the integrating adhesion mechanisms, but also the practical
      applications of utilizing and controlling the adhesive and frictional forces of
      gecko-inspired surfaces. 

PMID- 24041008
TI  - Maternal influenza-like illness, medication use during pregnancy and risk of
      congenital heart defects in offspring.
AB  - OBJECTIVE: To evaluate the association between maternal influenza and congenital
      heart defects (CHDs), and whether the use of traditional Chinese medicine (TCM)
      or Western medicine (antibiotics, antipyretic-analgesic drugs) modified this
      association. METHOD: We analysed 294 fetuses with CHDs and 416 control fetuses
      without any abnormalities identified from February 2010 through October 2011 in
      this hospital-based case-control study. Participating mothers were interviewed to
      determine whether they had been infected with "influenza" during the early
      pregnancy period or had used any medicine (TCM, Western medicine) to treat
      influenza. A logistic regression model was used to calculate ORs and 95% CIs
      while controlling for potential confounders. RESULTS: There were significant
      associations between maternal influenza and CHDs in the aggregate (AOR, 1.60;
      95%CI, 1.12 to 2.28) and specific subtypes, namely septal defects (AOR, 2.12;
      95%CI, 1.38 to 3.26) and conotruncal defects (AOR, 1.60; 95%CI, 1.01 to 2.51).
      Maternal medication use (i.e. TCM or Western medicine) in the setting of
      influenza tended to decrease these associations. CONCLUSIONS: Maternal influenza
      during second-third months of pregnancy increased the risk for CHDs, with septal
      defects and conotruncal defects in particular being observed. The use of
      medication for influenza might attenuate such associations.

PMID- 24041009
TI  - 2nd International Symposium on Gait and Balance in Multiple Sclerosis:
      interventions for gait and balance in MS.
AB  - PURPOSE: To provide a review of the 2nd International Symposium on Gait and
      Balance in Multiple Sclerosis (MS), emphasizing interventions in gait and balance
      for people with MS. METHOD: Review of current research on interventions used with
      people having MS and with people having other disorders that may provide novel
      insights into improving gait and balance and preventing falls in people with MS
      (pwMS). RESULTS: Nine speakers provided evidence-based recommendations for
      interventions aimed at improving gait and balance dysfunction. Speaker
      recommendations covered the following areas: balance rehabilitation, self
      management, medications, functional electrical stimulation, robotics, sensory
      augmentation, gait training with error feedback and fall prevention. CONCLUSIONS:
      The causes of gait and balance dysfunction in pwMS are multifactorial and
      therefore may benefit from a wide range of interventions. The symposium provides
      avenues for exchange of evidence and clinical experience that is critical in
      furthering physical rehabilitation including gait and balance dysfunction in MS.
      Implications for Rehabilitation Approaches to improve Gait and Balance
      dysfunction in Multiple Sclerosis. Balance exercises that include training of
      sensory strategies. Self-management and self-management support. Pharmacologic
      intervention, such as Dalfampradine. Functional electrical stimulation that may
      provide the extra stimulation to influence coordinated leg movements needed for
      walking.

PMID- 24041010
TI  - Extended antigen sparing potential of AS03-adjuvanted pandemic H1N1 vaccines in
      children, and immunological equivalence of two formulations of AS03-adjuvanted
      H1N1 vaccines: results from two randomised trials.
AB  - BACKGROUND: Pandemic influenza vaccine manufacturing capacity and distribution
      agility is enhanced through the availability of equivalent antigen-sparing
      vaccines. We evaluated equivalence in terms of immunogenicity between
      GlaxoSmithKline Vaccines' A/California/7/2009 (H1N1)v-like-AS03 vaccines
      manufactured in Dresden (D-Pan), and Quebec (Q-Pan). METHODS: In two studies, 334
      adults 18-60 years of age received 2 doses of D-Pan or Q-Pan containing 3.75 MUg
      haemagglutinin antigen (HA) adjuvanted with AS03A administered 21 days apart, and
      209 children 3-9 years of age received 1 reduced dose of D-Panor Q-Pan (0.9 MUg
      HA) or Q-Pan (1.9 MUg HA) with AS03B. Haemagglutination inhibition (HI) titres
      were assessed before and 21 days post-vaccination. HI persistence was assessed
      after 12 months in adults and 6 months in children. RESULTS: Pre-defined criteria
      for immunological equivalence of Q-Pan versus D-Pan were achieved in both
      populations. After one vaccine dose, >=97.6% of adults and children had HI titres
      >=1:40, with increases in titre >=25.7-fold. CHMP and CBER regulatory acceptance
      criteria for influenza vaccines were exceeded by all groups in both studies at
      Day 21. In adults,the percentage with HI titres >=1:40 at Month 12 was 82.9% (Q
      Pan) and 84.0% (D-Pan). In children, the percentages at Month 6 were 75.3.3% (Q
      Pan0.9), 85.1% (D-Pan0.9) and 79.3% (Q-Pan1.9). Safety profile of the study
      vaccines was consistent with previously published data. CONCLUSION: Two studies
      indicate that A/California/7/2009 (H1N1)v-like HA manufactured at two sites and
      combined with AS03 are equivalent in terms of immunogenicity in adults and
      children and highly immunogenic. Different HA doses elicited an adequate immune
      response through 180 days post-vaccination in children 3-9 years of age. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT00979407 and NCT01161160.

PMID- 24041011
TI  - Ability of HIV-1 Nef to downregulate CD4 and HLA class I differs among viral
      subtypes.
AB  - BACKGROUND: The highly genetically diverse HIV-1 group M subtypes may differ in
      their biological properties. Nef is an important mediator of viral pathogenicity;
      however, to date, a comprehensive inter-subtype comparison of Nef in vitro
      function has not been undertaken. Here, we investigate two of Nef's most well
      characterized activities, CD4 and HLA class I downregulation, for clones obtained
      from 360 chronic patients infected with HIV-1 subtypes A, B, C or D. RESULTS:
      Single HIV-1 plasma RNA Nef clones were obtained from N=360 antiretroviral-naive,
      chronically infected patients from Africa and North America: 96 (subtype A), 93
      (B), 85 (C), and 86 (D). Nef clones were expressed by transfection in an
      immortalized CD4+ T-cell line. CD4 and HLA class I surface levels were assessed
      by flow cytometry. Nef expression was verified by Western blot. Subset analyses
      and multivariable linear regression were used to adjust for differences in age,
      sex and clinical parameters between cohorts. Consensus HIV-1 subtype B and C Nef
      sequences were synthesized and functionally assessed. Exploratory sequence
      analyses were performed to identify potential genotypic correlates of Nef
      function. Subtype B Nef clones displayed marginally greater CD4 downregulation
      activity (p = 0.03) and markedly greater HLA class I downregulation activity (p <
      0.0001) than clones from other subtypes. Subtype C Nefs displayed the lowest in
      vitro functionality. Inter-subtype differences in HLA class I downregulation
      remained statistically significant after controlling for differences in age, sex,
      and clinical parameters (p < 0.0001). The synthesized consensus subtype B Nef
      showed higher activities compared to consensus C Nef, which was most pronounced
      in cells expressing lower protein levels. Nef clones exhibited substantial inter
      subtype diversity: cohort consensus residues differed at 25% of codons, while a
      similar proportion of codons exhibited substantial inter-subtype differences in
      major variant frequency. These amino acids, along with others identified in intra
      subtype analyses, represent candidates for mediating inter-subtype differences in
      Nef function. CONCLUSIONS: Results support a functional hierarchy of subtype B >
      A/D > C for Nef-mediated CD4 and HLA class I downregulation. The mechanisms
      underlying these differences and their relevance to HIV-1 pathogenicity merit
      further investigation.

PMID- 24041012
TI  - [18 F]FDG-PET imaging is an early non-invasive pharmacodynamic biomarker for a
      first-in-class dual MEK/Raf inhibitor, RO5126766 (CH5126766), in preclinical
      xenograft models.
AB  - BACKGROUND: Positron emission tomography (PET) with [2-18 F]-2-fluoro-2-deoxy-D
      glucose ([18 F]FDG-PET) was acquired at multiple time-points a) to monitor the
      early response to RO5126766 (CH5126766) in xenograft models b) to evaluate non
      invasive small animal [18 F]FDG-PET imaging as a biomarker for MEK inhibitors for
      translation into dose-finding studies in cancer patients and c) to explore the
      underlying mechanism related to FDG uptake in tumors treated with RO5126766.
      METHODS: [18 F]FDG uptake was studied in HCT116 (K-ras), COLO205 (B-raf) mutants
      and COLO320DM (wild type) xenografts from day 0 to 3 of RO5126766 treatment using
      a microPET Focus 120 and complemented with in vitro incubations, ex-vivo phosphor
      imaging and immunohistochemical (IHC) analyses. RESULTS: In the HCT116 (K-ras)
      and COLO205 (B-raf) mutant xenografts, significant decreases in [18 F]FDG uptake
      were detected in vivo on day 1 with 0.3 mg/kg and ex vivo on day 3 with 0.1 mg/kg
      RO5126766. [18 F]FDG changes correlated with decreases in tumor cells
      proliferation (Ki-67) and with changes in expression levels of GLUT1. No effects
      were observed in drug resistant COLO320DM cells. The cellular fractionation and
      Western blotting analyses suggested that the change of [18 F]FDG uptake
      associated with RO5126766 is due to translocation of GLUT1 from membrane to
      cytosol, similar to the results reported in the literature with EGFR tyrosine
      kinase inhibitors, which also target the MAPK pathway. CONCLUSIONS: RO5126766
      inhibition resulted in a rapid time - and dose - dependent decline in [18 F]FDG
      uptake in both mutant xenografts. These results strongly resemble the clinical
      observations obtained with MEK/Raf inhibitors support the use of preclinical [18
      F]FDG-PET as a translational tool for decision support in preclinical and early
      clinical development of MEK inhibitors.

PMID- 24041014
TI  - Free nitrous acid (FNA)-based pretreatment enhances methane production from waste
      activated sludge.
AB  - Anaerobic digestion of waste activated sludge (WAS) is currently enjoying renewed
      interest due to the potential for methane production. However, methane production
      is often limited by the slow hydrolysis rate and/or poor methane potential of
      WAS. This study presents a novel pretreatment strategy based on free nitrous acid
      (FNA or HNO2) to enhance methane production from WAS. Pretreatment of WAS for 24
      h at FNA concentrations up to 2.13 mg N/L substantially enhanced WAS
      solubilization, with the highest solubilization (0.16 mg chemical oxygen demand
      (COD)/mg volatile solids (VS), at 2.13 mg HNO2-N/L) being six times that without
      FNA pretreatment (0.025 mg COD/mg VS, at 0 mg HNO2-N/L). Biochemical methane
      potential tests demonstrated methane production increased with increased FNA
      concentration used in the pretreatment step. Model-based analysis indicated FNA
      pretreatment improved both hydrolysis rate and methane potential, with the
      highest improvement being approximately 50% (from 0.16 to 0.25 d(-1)) and 27%
      (from 201 to 255 L CH4/kg VS added), respectively, achieved at 1.78-2.13 mg HNO2
      N/L. Further analysis indicated that increased hydrolysis rate and methane
      potential were related to an increase in rapidly biodegradable substrates, which
      increased with increased FNA dose, while the slowly biodegradable substrates
      remained relatively static. 

PMID- 24041013
TI  - Topology of molecular interaction networks.
AB  - Molecular interactions are often represented as network models which have become
      the common language of many areas of biology. Graphs serve as convenient
      mathematical representations of network models and have themselves become objects
      of study. Their topology has been intensively researched over the last decade
      after evidence was found that they share underlying design principles with many
      other types of networks.Initial studies suggested that molecular interaction
      network topology is related to biological function and evolution. However,
      further whole-network analyses did not lead to a unified view on what this
      relation may look like, with conclusions highly dependent on the type of
      molecular interactions considered and the metrics used to study them. It is
      unclear whether global network topology drives function, as suggested by some
      researchers, or whether it is simply a byproduct of evolution or even an artefact
      of representing complex molecular interaction networks as graphs.Nevertheless,
      network biology has progressed significantly over the last years. We review the
      literature, focusing on two major developments. First, realizing that molecular
      interaction networks can be naturally decomposed into subsystems (such as modules
      and pathways), topology is increasingly studied locally rather than globally.
      Second, there is a move from a descriptive approach to a predictive one: rather
      than correlating biological network topology to generic properties such as
      robustness, it is used to predict specific functions or phenotypes.Taken
      together, this change in focus from globally descriptive to locally predictive
      points to new avenues of research. In particular, multi-scale approaches are
      developments promising to drive the study of molecular interaction networks
      further. 

PMID- 24041016
TI  - Optimizing electrostatic field calculations with the adaptive Poisson-Boltzmann
      Solver to predict electric fields at protein-protein interfaces. I. Sampling and
      focusing.
AB  - Continuum electrostatics methods are commonly used to calculate electrostatic
      potentials in proteins and at protein-protein interfaces to aid many types of
      biophysical studies. Despite their ubiquity throughout the biophysical
      literature, these calculations are difficult to test against experimental data to
      determine their accuracy and validity. To address this, we have calculated the
      Boltzmann-weighted electrostatic field at the midpoint of a nitrile bond placed
      at a variety of locations on the surface of the protein RalGDS, both in its
      monomeric form as well as when docked to four different constructs of the protein
      Rap, and compared the computation results to vibrational absorption energy
      measurements of the nitrile oscillator. This was done by generating a statistical
      ensemble of protein structures using enhanced molecular dynamics sampling with
      the Amber03 force field, followed by solving the linear Poisson-Boltzmann
      equation for each structure using the Applied Poisson-Boltzmann Solver (APBS)
      software package. Using a two-stage focusing strategy, we examined numerous
      second stage box dimensions, grid point densities, box locations, and compared
      the numerical result to the result obtained from the sum of the numeric reaction
      field and the analytic Coulomb field. It was found that the reaction field method
      yielded higher correlation with experiment for the absolute calculation of
      fields, while the numeric solutions yielded higher correlation with experiment
      for the relative field calculations. Finer grid spacing typically improved the
      calculation, although this effect was less pronounced in the reaction field
      method. These sorts of calculations were also very sensitive to the box location,
      particularly for the numeric calculations of absolute fields using a 10(3) A(3)
      box. 

PMID- 24041015
TI  - Reversal of established traumatic brain injury-induced, anxiety-like behavior in
      rats after delayed, post-injury neuroimmune suppression.
AB  - Abstract Traumatic brain injury (TBI) increases the risk of neuropsychiatric
      disorders, particularly anxiety disorders. Yet, there are presently no
      therapeutic interventions to prevent the development of post-traumatic anxiety or
      effective treatments once it has developed. This is because, in large part, of a
      lack of understanding of the underlying pathophysiology. Recent research suggests
      that chronic neuroinflammatory responses to injury may play a role in the
      development of post-traumatic anxiety in rodent models. Acute peri-injury
      administration of immunosuppressive compounds, such as Ibudilast (MN166), have
      been shown to prevent reactive gliosis associated with immune responses to injury
      and also prevent lateral fluid percussion injury (LFPI)-induced anxiety-like
      behavior in rats. There is evidence in both human and rodent studies that post
      traumatic anxiety, once developed, is a chronic, persistent, and drug-refractory
      condition. In the present study, we sought to determine whether neuroinflammation
      is associated with the long-term maintenance of post-traumatic anxiety. We
      examined the efficacy of an anti-inflammatory treatment in decreasing anxiety
      like behavior and reactive gliosis when introduced at 1 month after injury.
      Delayed treatment substantially reduced established LFPI-induced freezing
      behavior and reactive gliosis in brain regions associated with anxiety and
      continued neuroprotective effects were evidenced 6 months post-treatment. These
      results support the conclusion that neuroinflammation may be involved in the
      development and maintenance of anxiety-like behaviors after TBI. 

PMID- 24041018
TI  - [Twin studies in stomatology].
AB  - Twin studies are an important instrument to estimate the influence of genetics
      and environment on the origin of complex traits. The survey of the most important
      studies concerning oral facial region published from the half of the last century
      until recent days is given.

PMID- 24041017
TI  - The antiproliferative effect of Moringa oleifera crude aqueous leaf extract on
      cancerous human alveolar epithelial cells.
AB  - BACKGROUND: The incidence of lung cancer is expected to increase due to increases
      in exposure to airborne pollutants and cigarette smoke. Moringa oleifera (MO), a
      medicinal plant found mainly in Asia and South Africa is used in the traditional
      treatment of various ailments including cancer. This study investigated the
      antiproliferative effect of MO leaf extract (MOE) in cancerous A549 lung cells.
      METHODS: A crude aqueous leaf extract was prepared and the cells were treated
      with 166.7 MUg/ml MOE (IC50) for 24 h and assayed for oxidative stress (TBARS and
      Glutathione assays), DNA fragmentation (comet assay) and caspase (3/7 and 9)
      activity. In addition, the expression of Nrf2, p53, Smac/DIABLO and PARP-1 was
      determined by Western blotting. The mRNA expression of Nrf2 and p53 was assessed
      using qPCR. RESULTS: A significant increase in reactive oxygen species with a
      concomitant decrease in intracellular glutathione levels (p < 0.001) in MOE
      treated A549 cells was observed. MOE showed a significant reduction in Nrf2
      protein expression (1.89-fold, p < 0.05) and mRNA expression (1.44-fold). A
      higher level of DNA fragmentation (p < 0.0001) was seen in the MOE treated cells.
      MOE's pro-apoptotic action was confirmed by the significant increase in p53
      protein expression (1.02-fold, p < 0.05), p53 mRNA expression (1.59-fold),
      caspase-9 (1.28-fold, p < 0.05), caspase-3/7 (1.52-fold) activities and an
      enhanced expression of Smac/DIABLO. MOE also caused the cleavage and activation
      of PARP-1 into 89 KDa and 24 KDa fragments (p < 0.0001). CONCLUSION: MOE exerts
      antiproliferative effects in A549 lung cells by increasing oxidative stress, DNA
      fragmentation and inducing apoptosis.

PMID- 24041019
TI  - [Heredity of orthodontic anomalies].
AB  - The survey of most common orthodontic anomalies is given in this article.
      Authors, utilizing literature data, their own research as well as their
      therapeutic experience, try to elucidate the role of genetics in determination of
      dental anomalies and malocclusion. They emphasise the fact that genetically
      determined orthodontic anomalies are not easy to treat. Retention of treatment
      result could also be a problem. Occurrence of an anomaly in one member of the
      family should lead to the examination of other members, especially the young
      ones.

PMID- 24041020
TI  - [The clefts as inborn defects].
AB  - The article refers usual facial clefts, which are not rare anomalies. Relation to
      other forms of so-called midline defects (limb clefts) is indicated. Syndromic
      and unusual clefts are rarer than isolated non-syndromic clefts. Clinical
      features, including minimal symptomatology, etiopathogenesis and population
      frequency are discussed. From the diagnostic point of view specific, prenatal,
      postnatal and differential diagnostic approaches are recognized. Preventive
      aspects, therapy and management of the disease (for cleft lip and palate defects,
      median cleft palate, broad spectrum of neural tube defects including anencephaly,
      limb clefts etc.) are important. We estimated the empiric risk of the recurrence
      and suggest methods for preconceptional preventive care.

PMID- 24041021
TI  - [Orthodontic anomalies and secular trend in formation of the orofacial cranium].
AB  - BACKGROUND. The aim of the study was to compare craniofacial and dental
      characteristics of contemporary and historical populations and elucidate some
      etiological aspects of malocclusion. METHODS AND RESULTS. Con-temporary cohort of
      703 university students and three historical samples (73 skulls from 9th century,
      344 skulls from the 10th to 14th century and 210 skulls from the 14th to 18th
      century were examined. Measurements of craniometric and anthropometric points
      were done. The width of jaws was examined in Pont's points. Bjork's method for
      epidemiological registration of malocclusion was used; teleroentgenograms were
      examined as well. Broader dental arches regardless of the type of skull and
      significantly lower frequency of serious malocclusions were proven in historical
      population. CONCLUSION. The extreme increase of serious malocclusions in the
      contemporary population is more probably caused by civilisation factors than
      secular trend in formation of skull. .

PMID- 24041022
TI  - [Evaluation of the dental pathology in archaeological skeletal material:
      prevalence of dental caries since prehistory to modern age].
AB  - BACKGROUND: The evaluation of the dental health of past populations is an
      important part of the anthropological analysis of human skeletal remains
      uncovered during the archaeological excavations. The results provide the
      important information not only of the overall health of past populations, but
      also are reflective of the nutrition or the social status of our ancestors. We
      focused on the comparison of dental caries from prehistoric times to the present
      day. The aim was to evaluate the dental decay in several prehistoric, Early
      Medieval and modern populations and determine whether and to what extent the
      decay differ between the individual groups. METHODS AND RESULTS. We observed the
      permanent dentition in adult men and females, who were divided into three groups:
      the population of the younger Eneolithic to the Bronze Age, the population of the
      Early Middle Ages and the population of the modern times. We used the Index of
      Intensity of Caries I-CE and the Index of Caries Frequency F-CE to evaluate the
      incidence of caries and intra-vital losses. The comparison was carried out
      between groups, between both of jaws and between individual teeth. We took into
      account sex and age of the individuals studied. The highest value of F-CE was set
      in the population of the modern times (67.5). The difference in caries frequency
      among populations was not significant. The intensity of caries was the highest in
      modern population (I-CE: 13.2). Compared with the two older populations the
      difference was statistically highly significant (p 0.001).With regard to sex, the
      results differed between populations. It could be caused by a different frequency
      of men and females in individual groups.The correlation of intensity of caries
      with age was confirmed. Some partial results were affected by unequal frequency
      of age categories. CONCLUSION. The results showed the worst dental health in the
      population of the modern times. The null hypothesis,that tooth decay among the
      individual populations from different periods is not different, was rejected. The
      results must be interpreted with regard to the demographic composition of the
      files researched.

PMID- 24041023
TI  - [First results of participation of the Czech Republic in the 7th Framework
      Programme, priority Health, in years 2007-2013].
AB  - European Commission has announced the first preliminary results of participation
      in the 7th Framework Programme (FP7), priority Health. The overview presents the
      basic statistics regarding the participation of the Czech teams, universities,
      institutions, and small and medium size enterprises (SMEs) in FP7 projects. The
      aim of the article is to present the basic data on the projects with the Czech
      participation, the EU financial contribution for Czech teams and the main
      research topics.

PMID- 24041024
TI  - Hybrid and nonhybrid lipids exert common effects on membrane raft size and
      morphology.
AB  - Nanometer-scale domains in cholesterol-rich model membranes emulate lipid rafts
      in cell plasma membranes (PMs). The physicochemical mechanisms that maintain a
      finite, small domain size are, however, not well understood. A special role has
      been postulated for chain-asymmetric or hybrid lipids having a saturated sn-1
      chain and an unsaturated sn-2 chain. Hybrid lipids generate nanodomains in some
      model membranes and are also abundant in the PM. It was proposed that they align
      in a preferred orientation at the boundary of ordered and disordered phases,
      lowering the interfacial energy and thus reducing domain size. We used small
      angle neutron scattering and fluorescence techniques to detect nanoscopic and
      modulated liquid phase domains in a mixture composed entirely of nonhybrid lipids
      and cholesterol. Our results are indistinguishable from those obtained previously
      for mixtures containing hybrid lipids, conclusively showing that hybrid lipids
      are not required for the formation of nanoscopic liquid domains and strongly
      implying a common mechanism for the overall control of raft size and morphology.
      We discuss implications of these findings for theoretical descriptions of
      nanodomains. 

PMID- 24041027
TI  - Resveratrol induces hepatic mitochondrial biogenesis through the sequential
      activation of nitric oxide and carbon monoxide production.
AB  - AIMS: Nitric oxide (NO) can induce mitochondrial biogenesis in cultured cells,
      through increased guanosine 3',5'-monophosphate (cGMP), and activation of
      peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha).
      We sought to determine the role of NO, heme oxygenase-1 (HO-1), and its reaction
      product (carbon monoxide [CO]) in the induction of mitochondrial biogenesis by
      the natural antioxidant resveratrol. RESULTS: S-nitroso-N-acetylpenicillamine
      (SNAP), an NO donor, induced mitochondrial biogenesis in HepG2 hepatoma cells,
      and in vivo, through stimulation of PGC-1alpha. NO-induced mitochondrial
      biogenesis required cGMP, and was mimicked by the cGMP analogue (8-bromoguanosine
      3',5'-cyclic monophosphate [8-Br-cGMP]). Activation of mitochondrial biogenesis
      by SNAP required HO-1, as it could be reversed by genetic interference of HO-1;
      and by treatment with the HO inhibitor tin-protoporphyrin-IX (SnPP) in vitro and
      in vivo. Cobalt protoporphyrin (CoPP)-IX, an HO-1 inducing agent, stimulated
      mitochondrial biogenesis in HepG2 cells, which could be reversed by the CO
      scavenger hemoglobin. Application of CO, using the CO-releasing molecule-3 (CORM
      3), stimulated mitochondrial biogenesis in HepG2 cells, in a cGMP-dependent
      manner. Both CoPP and CORM-3-induced mitochondrial biogenesis required NF-E2
      related factor-2 (Nrf2) activation and phosphorylation of Akt. The natural
      antioxidant resveratrol induced mitochondrial biogenesis in HepG2 cells, in a
      manner dependent on NO biosynthesis, cGMP synthesis, Nrf2-dependent HO-1
      activation, and endogenous CO production. Furthermore, resveratrol preserved
      mitochondrial biogenesis during lipopolysaccharides-induced hepatic inflammation
      in vivo. INNOVATION AND CONCLUSIONS: The complex interplay between endogenous NO
      and CO production may underlie the mechanism by which natural antioxidants induce
      mitochondrial biogenesis. Strategies aimed at improving mitochondrial biogenesis
      may be used as therapeutics for the treatment of diseases involving mitochondrial
      dysfunction.

PMID- 24041028
TI  - The effect of arm position on the ultrasonographic measurements of the acromion
      greater tuberosity distance.
AB  - Ultrasonographic measurements of acromion-greater tuberosity (AGT) distance have
      shown to be reliable and valid in the assessment of glenohumeral subluxation
      (GHS) in patients with stroke. The primary aim of this study was to investigate
      the effect of arm positions on ultrasonographic measurements of AGT distance. The
      secondary aim was to assess the intra-rater reliability of AGT distance in
      different arm positions. Sixteen healthy individuals with a mean age 28 standard
      deviation 11 years who gave informed written consent were recruited. Four
      clinically relevant arm positions for patients with stroke were selected: (1) arm
      hanging freely by the side; (2) forearm on a pillow placed on participants lap
      with the elbows at 90 degrees  flexion and the forearms in pronation; (3) as in
      position 2, but with the elbow supported and (4) shoulder in 10 degrees  of
      abduction and 60 degrees  of flexion with the arm resting on a pillow placed on a
      table. Repeated measures analysis of variance showed a statistically significant
      effect of arm positions on mean AGT measurements for the right (F (3, 45) =
      51.2666, p < 0.001, effect size = 0.774) and left (F (3, 45) = 51.883, p < 0.001,
      effect size = 0.776) shoulders. AGT distance was significantly reduced in
      positions 3 and 4. Within-session intra-class correlation coefficients and the
      minimum detectable change values ranged from 0.94 to 0.97 and 0.1 to 0.2 cm,
      respectively, for all four positions. This preliminary study corroborates that
      supported arm position does reduce the AGT distance in healthy people suggesting
      ultrasonographic technique has potential to provide objective measurements in
      clinical management of patients with GHS.

PMID- 24041029
TI  - MicroRNA-21 regulates stemness in cancer cells.
AB  - MicroRNA-21 (miR-21) functions have been linked to cancer progression and chemo-
      or radiotherapy resistance. While an increasing number of studies have reported a
      potential role of miR-21 expression in promoting growth of a small population of
      stem/progenitor cells, knowledge on its role as a regulator of stemness in
      cancers remains limited. In a previous issue of Stem Cell Research & Therapy,
      Chung and colleagues provide evidence that miR-21 is highly expressed in
      stem/progenitor populations of ovarian teratocarcinoma cells and has the
      potential to mediate growth and self-renewal in cancer stem/progenitor cells.
      Here we summarize current knowledge on miR-21 functions in human cancers and
      discuss how this finding provides insight into the role of miR-21 as an oncogenic
      regulator in stem/progenitor cell populations of human cancers.

PMID- 24041030
TI  - Multiplex iterative plasmid engineering for combinatorial optimization of
      metabolic pathways and diversification of protein coding sequences.
AB  - Engineering complex biological systems typically requires combinatorial
      optimization to achieve the desired functionality. Here, we present Multiplex
      Iterative Plasmid Engineering (MIPE), which is a highly efficient and customized
      method for combinatorial diversification of plasmid sequences. MIPE exploits
      ssDNA mediated lambda Red recombineering for the introduction of mutations,
      allowing it to target several sites simultaneously and generate libraries of up
      to 10(7) sequences in one reaction. We also describe "restriction digestion
      mediated co-selection (RD CoS)", which enables MIPE to produce enhanced
      recombineering efficiencies with greatly simplified coselection procedures. To
      demonstrate this approach, we applied MIPE to fine-tune gene expression level in
      the 5-gene riboflavin biosynthetic pathway and successfully isolated a clone with
      2.67-fold improved production in less than a week. We further demonstrated the
      ability of MIPE for highly multiplexed diversification of protein coding sequence
      by simultaneously targeting 23 codons scattered along the 750 bp sequence. We
      anticipate this method to benefit the optimization of diverse biological systems
      in synthetic biology and metabolic engineering.

PMID- 24041031
TI  - Relationship between oxidant and antioxidant activity in hyperemesis gravidarum.
AB  - OBJECTIVE: To evaluate oxidant and antioxidant activity in patients with
      hyperemesis gravidarum (HG) by using serum total antioxidant activity (TAO),
      total free sulfhydryl (-SH), ceruloplasmin and lipid hydroperoxide (LOOH) levels.
      MATERIALS AND METHODS: In a cross-sectional trial, blood samples were collected
      from patients with HG (n = 25) and healthy pregnant women (n = 25) as control
      group. Serum TAO activities, -SH levels and LOOH levels and ceruloplasmin levels
      were measured. RESULTS: Serum TAO activity was found to be significantly lower (p
      = 0.003) in patients with HG compared with controls. However, serum -SH levels,
      LOOH levels and ceruloplasmin levels did not change significantly in patients
      with HG compared to controls. CONCLUSION: Presence of oxidative stress in HG
      patients depends more on reduced antioxidant activities than increased oxidative
      stress.

PMID- 24041032
TI  - Relationship between social anxiety and perceived trustworthiness.
AB  - Four different patterns of biased ratings of facial expressions of emotions have
      been found in socially anxious participants: higher negative ratings of (1)
      negative, (2) neutral, and (3) positive facial expressions than nonanxious
      controls. As a fourth pattern, some studies have found no group differences in
      ratings of facial expressions of emotion. However, these studies usually employed
      valence and arousal ratings that arguably may be less able to reflect processing
      of social information. We examined the relationship between social anxiety and
      face ratings for perceived trustworthiness given that trustworthiness is an
      inherently socially relevant construct. Improving on earlier analytical
      strategies, we evaluated the four previously found result patterns using a
      Bayesian approach. Ninety-eight undergraduates rated 198 face stimuli on
      perceived trustworthiness. Subsequently, participants completed social anxiety
      questionnaires to assess the severity of social fears. Bayesian modeling
      indicated that the probability that social anxiety did not influence judgments of
      trustworthiness had at least three times more empirical support in our sample
      than assuming any kind of negative interpretation bias in social anxiety. We
      concluded that the deviant interpretation of facial trustworthiness is not a
      relevant aspect in social anxiety. 

PMID- 24041033
TI  - Facioscapulohumeral muscular dystrophy and Charcot-Marie-Tooth neuropathy 1A -
      evidence for "double trouble" overlapping syndromes.
AB  - BACKGROUND: We report on a patient with genetically confirmed overlapping
      diagnoses of CMT1A and FSHD. This case adds to the increasing number of unique
      patients presenting with atypical phenotypes, particularly in FSHD. Even if a
      mutation in one disease gene has been found, further genetic testing might be
      warranted in cases with unusual clinical presentation. CASE PRESENTATION: The
      reported 53 years old male patient suffered from walking difficulties and foot
      deformities first noticed at age 20. Later on, he developed scapuloperoneal and
      truncal muscle weakness, along with atrophy of the intrinsic hand and foot
      muscles, pes cavus, claw toes and a distal symmetric hypoesthesia. Motor nerve
      conduction velocities were reduced to 20 m/s in the upper extremities, and not
      educible in the lower extremities, sensory nerve conduction velocities were not
      attainable. Electromyography showed both, myopathic and neurogenic changes. A
      muscle biopsy taken from the tibialis anterior muscle showed a mild myopathy with
      some neurogenic findings and hypertrophic type 1 fibers. Whole-body muscle MRI
      revealed severe changes in the lower leg muscles, tibialis anterior and
      gastrocnemius muscles were highly replaced by fatty tissue. Additionally, fatty
      degeneration of shoulder girdle and straight back muscles, and atrophy of dorsal
      upper leg muscles were seen. Taken together, the presenting features suggested
      both, a neuropathy and a myopathy. Patient's family history suggested an
      autosomal dominant inheritance.Molecular testing revealed both, a hereditary
      motor and sensory neuropathy type 1A (HMSN1A, also called Charcot-Marie-Tooth
      neuropathy 1A, CMT1A) due to a PMP22 gene duplication and facioscapulohumeral
      muscular dystrophy (FSHD) due to a partial deletion of the D4Z4 locus (19 kb).
      CONCLUSION: Molecular testing in hereditary neuromuscular disorders has led to
      the identification of an increasing number of atypical phenotypes. Nevertheless,
      finding the right diagnosis is crucial for the patient in order to obtain
      adequate medical care and appropriate genetic counseling, especially in the
      background of arising curative therapies.

PMID- 24041034
TI  - Linkages between HIV-1 specificity for CCR5 or CXCR4 and in vitro usage of
      alternative coreceptors during progressive HIV-1 subtype C infection.
AB  - BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype C (C-HIV) is
      spreading rapidly and is now responsible for >50% of HIV-1 infections worldwide,
      and >95% of infections in southern Africa and central Asia. These regions are
      burdened with the overwhelming majority of HIV-1 infections, yet we know very
      little about the pathogenesis of C-HIV. In addition to CCR5 and CXCR4, the HIV-1
      envelope glycoproteins (Env) may engage a variety of alternative coreceptors for
      entry into transfected cells. Whilst alternative coreceptors do not appear to
      have a broad role in mediating the entry of HIV-1 into primary cells,
      characterizing patterns of alternative coreceptor usage in vitro can provide
      valuable insights into mechanisms of Env-coreceptor engagement that may be
      important for HIV-1 pathogenesis. RESULTS: Here, we characterized the ability of
      luciferase reporter viruses pseudotyped with HIV-1 Envs (n = 300) cloned
      sequentially from plasma of 21 antiretroviral therapy (ART)-naive subjects
      experiencing progression from chronic to advanced C-HIV infection over an
      approximately 3-year period, who either exclusively maintained CCR5-using (R5)
      variants (n = 20 subjects) or who experienced a coreceptor switch to CXCR4-using
      (X4) variants (n = 1 subject), to utilize alternative coreceptors for entry. At a
      population level, CCR5 usage by R5 C-HIV Envs was strongly linked to usage of
      FPRL1, CCR3 and CCR8 as alternative coreceptors, with the linkages to FPRL1 and
      CCR3 usage becoming statistically more robust as infection progressed from
      chronic to advanced stages of disease. In contrast, acquisition of an X4 Env
      phenotype at advanced infection was accompanied by a dramatic loss of FPRL1
      usage. Env mutagenesis studies confirmed a direct link between CCR5 and FPRL1
      usage, and showed that the V3 loop crown, but not other V3 determinants of CCR5
      specificity, was the principal Env determinant governing the ability of R5 C-HIV
      Envs from one particular subject to engage FPRL1. CONCLUSIONS: Our results
      suggest that, in the absence of coreceptor switching, the ability of R5 C-HIV
      viruses to engage certain alternative coreceptors in vitro, in particular FPRL1,
      may reflect an altered use of CCR5 that is selected for during progressive C-HIV
      infection, and which may contribute to C-HIV pathogenicity.

PMID- 24041035
TI  - 18 F-click labeling and preclinical evaluation of a new 18 F-folate for PET
      imaging.
AB  - BACKGROUND: The folate receptor (FR) is a well-established target for tumor
      imaging and therapy. To date, only a few 18 F-folate conjugates via 18 F
      prosthetic group labeling for positron emission tomography (PET) imaging have
      been developed. To some extent, they all lack the optimal balance between
      efficient radiochemistry and favorable in vivo characteristics. METHODS: A new
      clickable olate precursor was synthesized by regioselective coupling of folic
      acid to 11-azido-3,6,9-trioxaundecan-1-amine at the gamma-position of the
      glutamic acid residue. The non-radioactive reference compound was synthesized via
      copper-catalyzed azide-alkyne cycloaddition of 3-(2-(2-(2
      fluoroethoxy)ethoxy)ethoxy)prop-1-yne and gamma-(11-azido-3,6,9
      trioxaundecanyl)folic acid amide. The radiosynthesis was accomplished in two
      steps: at first a 18 F-fluorination of 2-(2-(2-(prop-2-yn-1
      yloxy)ethoxy)ethoxy)ethyl-4-methylbenzenesulfonate, followed by a 18 F-click
      reaction with the gamma-azido folate. The in vitro, ex vivo, and in vivo
      behaviors of the new 18 F-folate were investigated using FR-positive human KB
      cells in displacement assays and microPET studies using KB tumor-bearing mice.
      RESULTS: The new 18 F-folate with oligoethylene spacers showed reduced
      lipophilicity in respect to the previously developed 18 F-click folate with alkyl
      spacers and excellent affinity (Ki = 1.6 nM) to the FR. Combining the highly
      efficient 18 F-click chemistry and a polar oligoethylene-based 18 F-prosthetic
      group facilitated these results. The overall radiochemical yield of the isolated
      and formulated product averages 8.7%. In vivo PET imaging in KB tumor-bearing
      mice showed a tumor uptake of 3.4% ID/g tissue, which could be reduced by FR
      blockade with native folic acid. Although the new 18 F-oligoethyleneglycole (OEG)
      folate showed reduced hepatobiliary excretion over time, a distinct unspecific
      abdominal background was still observed. CONCLUSIONS: A new 18 F-folate was
      developed, being available in very high radiochemical yields via a fast and
      convenient two-step radiosynthesis. The new 18 F-OEG-folate showed good in vivo
      behavior and lines up with several recently evaluated 18 F-labeled folates.

PMID- 24041036
TI  - Counselling in humanitarian settings: a retrospective analysis of 18 individual
      focused non-specialised counselling programmes.
AB  - BACKGROUND: Medecins Sans Frontieres (MSF) provides individual counselling
      interventions in medical humanitarian programmes in contexts affected by conflict
      and violence. Although mental health and psychosocial interventions are a common
      part of the humanitarian response, little is known about how the profile and
      outcomes for individuals seeking care differs across contexts. We did a
      retrospective analysis of routine programme data to determine who accessed MSF
      counselling services and why, and the individual and programmatic risk factors
      for poor outcomes. METHODS: We analysed data from 18 mental health projects run
      by MSF in 2009 in eight countries. Outcome measures were client-rating scores (1
      10 scale; 1 worst) for complaint severity and functioning and counsellor
      assessment. The effect of client and programme factors on outcomes was assessed
      by multiple regression analysis. Logistic regression was used to assess binary
      outcome variables. RESULTS: 48704 counselling sessions were held with 14963
      individuals. Excluding women-focused projects, 66.8% of patients were women. Mean
      (SD) age was 33.3 (14.1) years. Anxiety-related complaints were the most common
      (35.0%), followed by family-related problems (15.7%), mood-related problems
      (14.1%) and physical complaints (13.7%). Only 2.0% presented with a serious
      mental health condition. 27.2% did not identify a traumatic precipitating event.
      24.6% identified domestic discord or violence and 17.5% psychological violence as
      the precipitating event. 6244 (43.9%) had only one session. For 91% of 7837 who
      returned, the counsellor reported the problem had decreased or resolved. The mean
      (SD) complaint rating improved by 4.7 (2.4) points (p < 0.001) and by 4.2 (2.3, p
      < 0.001) for functional rating. Risk factors for poorer outcomes were few
      sessions, non-conflict setting (stable or societal violence settings), serious
      mental health condition, or attending a large, recently opened project.
      CONCLUSIONS: The majority of clients accessing counselling services present with
      anxiety related complaints. Attrition rates were high. Good outcomes were
      recorded among those who attended for more than one visit. Lessons learned
      included the importance of adaptation of approach in non-conflict contexts such
      as societal violence or post-conflict contexts. There is a need for further
      research to evaluate the intervention against a control group.

PMID- 24041038
TI  - Why single-beam optical tweezers trap gold nanowires in three dimensions.
AB  - Understanding whether noble-metal nanostructures can be trapped optically and
      under what conditions will enable a range of applications that exploit their
      plasmonic properties. However, there are several nontrivial issues that first
      need to be resolved. A major one is that metal particles experience strong
      radiation pressure in optical beams, while stable optical trapping requires an
      attractive force greater than this radiation pressure. Therefore, it has
      generally been considered impossible to obtain sufficiently strong gradient
      forces using single-beam optical tweezers to trap relatively large metal
      nanostructures in three dimensions. Here we demonstrate that a single, tightly
      focused laser beam with a wavelength of 800 nm can achieve three-dimensional
      optical trapping of individual gold (Au) nanowires with lengths over 2 MUm.
      Nanowires can be trapped by the beam at one of their ends, in which case they
      undergo significant angular fluctuations due to Brownian motion of the untrapped
      end. They can also be trapped close to their midpoints, in which case they are
      oriented approximately perpendicular to the light polarization direction. The
      behavior is markedly different from that of Ag nanowires with similar length and
      diameter, which cannot be trapped in three dimensions by a single focused
      Gaussian beam. Our results, including electrodynamics simulations that help to
      explain our experimental findings, suggest that the conventional wisdom, which
      holds that larger metal particles cannot be trapped, needs to be replaced with an
      understanding based on the details of plasmon resonances in the particles. 

PMID- 24041041
TI  - [Refractory gastroesophageal reflux disease (GERD) and PPI safety].

PMID- 24041039
TI  - Metabolic markers and microecological characteristics of tongue coating in
      patients with chronic gastritis.
AB  - BACKGROUND: In Traditional Chinese Medicine (TCM), tongue diagnosis has been an
      important diagnostic method for the last 3000 years. Tongue diagnosis is a non
      invasive, simple and valuable diagnostic tool. TCM treats the tongue coating on a
      very sensitive scale that reflects physiological and pathological changes in the
      organs, especially the spleen and stomach. Tongue coating can diagnose disease
      severity and determine the TCM syndrome ("Zheng" in Chinese). The biological
      bases of different tongue coating appearances are still poorly understood and
      lack systematic investigation at the molecular level. METHODS: Tongue coating
      samples were collected from 70 chronic gastritis patients and 20 normal controls.
      16S rRNA denatured gradient gel electrophoresis (16S rRNA-DGGE) and liquid
      chromatography and mass spectrometry (LC-MS) were designed to profile tongue
      coatings. The statistical techniques used were principal component analysis and
      partial least squares-discriminate analysis. RESULTS: Ten potential metabolites
      or markers were found in chronic gastritis patients, including UDP-D-galactose, 3
      ketolactose, and vitamin D2, based on LC-MS. Eight significantly different strips
      were observed in samples from chronic gastritis patients based on 16S rRNA-DGGE.
      Two strips, Strips 8 and 10, were selected for gene sequencing. Strip 10
      sequencing showed a 100% similarity to Rothia mucilaginosa. Strip 8 sequencing
      showed a 96.2% similarity to Moraxella catarrhalis. CONCLUSIONS: Changes in
      glucose metabolism could possibly form the basis of tongue coating conformation
      in chronic gastritis patients. The study revealed important connections between
      metabolic components, microecological components and tongue coating in chronic
      gastritis patients. Compared with other diagnostic regimens, such as blood tests
      or tissue biopsies, tongue coating is more amenable to, and more convenient for,
      both patients and doctors.

PMID- 24041037
TI  - Applications of technology in neuropsychological assessment.
AB  - Most neuropsychological assessments include at least one measure that is
      administered, scored, or interpreted by computers or other technologies. Despite
      supportive findings for these technology-based assessments, there is resistance
      in the field of neuropsychology to adopt additional measures that incorporate
      technology components. This literature review addresses the research findings of
      technology-based neuropsychological assessments, including computer- and virtual
      reality-based measures of cognitive and functional abilities. We evaluate the
      strengths and limitations of each approach, and examine the utility of technology
      based assessments to obtain supplemental cognitive and behavioral information
      that may be otherwise undetected by traditional paper-and-pencil measures. We
      argue that the potential of technology use in neuropsychological assessment has
      not yet been realized, and continued adoption of new technologies could result in
      more comprehensive assessment of cognitive dysfunction and in turn, better
      informed diagnosis and treatments. Recommendations for future research are also
      provided. 

PMID- 24041042
TI  - [Eosinophilic esophagitis].

PMID- 24041043
TI  - [Peptic ulcer, NSAID and Helicobacter].

PMID- 24041044
TI  - [Barrett's esophagus (Diagnostic and treatment updates)].

PMID- 24041045
TI  - [Premalignant lesions. Diagnosis and treatment of incipient gastric cancer].

PMID- 24041046
TI  - [Neoplastic lesions of the colon: endoscopic diagnosis and treatment].

PMID- 24041047
TI  - [Neoplastic lesions of the digestive tract: diagnosis and treatment through
      imaging].

PMID- 24041048
TI  - [Update on celiac disease diagnosis].

PMID- 24041049
TI  - [Intestinal microbiota in digestive disorders. Probiotics, prebiotics and
      symbiotics].

PMID- 24041050
TI  - [Esophageal functional disorders].

PMID- 24041051
TI  - [Dyspepsia and gastroparesis].

PMID- 24041052
TI  - [Irritable Bowel Syndrome (IBS) in the 2013 DDW].

PMID- 24041053
TI  - [Constipation and functional anorectal disorders].

PMID- 24041054
TI  - [Acute pancreatitis].

PMID- 24041055
TI  - [Chronic pancreatitis and autoimmune pancreatitis].

PMID- 24041056
TI  - [Pancreatic neoplasms].

PMID- 24041057
TI  - [Endoscopic treatment of pancreatic diseases].

PMID- 24041058
TI  - [Enteroscopy].

PMID- 24041059
TI  - [Endoscopic capsule].

PMID- 24041060
TI  - [Advances in endoscopic ultrasound].

PMID- 24041061
TI  - [Biliary tract endoscopy].

PMID- 24041062
TI  - [New technologies in endoscopy].

PMID- 24041063
TI  - [Advances in the diagnosis, pathophysiology and treatment of chronic non-specific
      ulcerative colitis].

PMID- 24041064
TI  - [Crohn's disease: diagnosis and treatment].

PMID- 24041065
TI  - [Microscopic colitis and other colitis].

PMID- 24041066
TI  - [Chronic and infectious diarrheas].

PMID- 24041067
TI  - [Biliary tract surgery].

PMID- 24041068
TI  - [POEM and endoscopic surgery in achalasia].

PMID- 24041069
TI  - [Paradigm shift in diverticulitis].

PMID- 24041070
TI  - [Obesity surgery].

PMID- 24041071
TI  - [Hepatitis B].

PMID- 24041072
TI  - [Chronic hepatitis C].

PMID- 24041073
TI  - [Steatosis and non-alcoholic steatohepatitis].

PMID- 24041074
TI  - [Cholestasis and autoimmune hepatitis].

PMID- 24041075
TI  - [Fulminant hepatitis].

PMID- 24041076
TI  - [Complications of cirrhosis: encephalopathy, nutritional status, and ascites].

PMID- 24041077
TI  - [Alcoholic hepatitis].

PMID- 24041078
TI  - [Hepatocellular carcinoma].

PMID- 24041079
TI  - [Clinical liver transplantation].

PMID- 24041080
TI  - [Surgical aspects of liver transplantation].

PMID- 24041081
TI  - [Pediatric hepatology].

PMID- 24041082
TI  - Catalysis by desolvation: the catalytic prowess of SAM-dependent halide
      alkylating enzymes.
AB  - In the biological fixation of halide ions, several enzymes have been found to
      catalyze alkyl transfer from S-adenosylmethionine to halide ions. It proves
      possible to measure the rates of reaction of the trimethylsulfonium ion with I(
      ), Br(-), Cl(-), F(-), HO(-), and H2O in water at elevated temperatures.
      Comparison of the resulting second-order rate constants, extrapolated to 25 
      degrees C, with the values of k(cat)/K(m) reported for fluorinase and chlorinase
      indicates that these enzymes enhance the rates of alkyl halide formation by
      factors of 2 * 10(15)- and 1 * 10(17)-fold, respectively. These rate
      enhancements, achieved without the assistance of cofactors, metal ions, or
      general acid-base catalysis, are the largest that have been reported for an
      enzyme that acts on two substrates.

PMID- 24041088
TI  - Coherent exciton delocalization in strongly coupled quantum dot arrays.
AB  - Quantum dots (QDs) coupled into disordered arrays have exhibited the intriguing
      property of bulk-like transport while maintaining discrete excitonic optical
      transitions. We have utilized ultrafast cross-polarized transient grating (CPTG)
      spectroscopy to measure electron-hole wave function overlap in CdSe QD films with
      chemically modified surfaces for tuning inter-QD electronic coupling. By
      comparing the CPTG decays with those of isolated QDs, we find that excitons
      coherently delocalize to form excited states more than 200% larger than the QD
      diameter. 

PMID- 24041089
TI  - Nanopore surface coating delivers nanopore size and shape through conductance
      based sizing.
AB  - The performance of nanopore single-molecule sensing elements depends intimately
      on their physical dimensions and surface chemical properties. These factors
      underpin the dependence of the nanopore ionic conductance on electrolyte
      concentration, yet the measured, or modeled, dependence only partially
      illuminates the details of geometry and surface chemistry. Using the electrolyte
      dependent conductance data before and after selective surface functionalization
      of solid-state nanopores, however, introduces more degrees of freedom and
      improves the performance of conductance-based nanopore characterizations. Sets of
      representative nanopore profiles were used to generate conductance data, and the
      nanopore shape and exact dimensions were identified, through conductance alone,
      by orders-of-magnitude reductions in the geometry optimization metrics. The
      optimization framework could similarly be used to evaluate the nanopore surface
      coating thickness. 

PMID- 24041092
TI  - International out of programme experience (OOPE): is it worthwhile?

PMID- 24041093
TI  - Role models in primary care education: inescapable but forgotten?

PMID- 24041094
TI  - Evidence-based practice: missed learning opportunities in undergraduate primary
      care?

PMID- 24041095
TI  - Prepared for commissioning? A qualitative study into the views of recently
      qualified GPs.
AB  - BACKGROUND: Expectations of the latest manifestation of GPled commissioning, in
      delivering cost-savings and improved services, are considerable. However,
      previous models suggest clinical engagement and other factors may hinder its
      success. It is timely to explore the views of the newest generation of GPs about
      involvement in commissioning, to inform plans for preparing the future workforce.
      AIM: To explore the views of recently qualified GPs about their future role in
      commissioning health services. DESIGN AND SETTING: A qualitative study with GPs
      qualifying with Severn Deanery between 2007 and 2010. METHOD: Semi-structured
      interviews with 18 GPs between November 2011 and April 2012. RESULTS: These GPs
      lack understanding of roles and skills required for commissioning. Readiness is
      related to experience as a GP and of how services are financed and run, making
      timeliness for becoming involved important. Not all GPs feel motivated for
      commissioning and readiness is further hindered by feelings of conflict and
      uncertainty about how commissioning will work. There is optimism around working
      differently and better representing patients, but caution around risks and for
      some, cynicism about motives, will need addressing. CONCLUSION: While there is
      some optimism among these GPs about representing patients, leading reform and
      working differently with colleagues, there are concerns. GPs need to better
      understand the processes involved, experience and skills needed, and roles they
      can take. They can be helped through education and mentoring by established GPs
      to be ready for a role in commissioning.

PMID- 24041096
TI  - The views and experiences of female GPs on professional practice and career
      support.
AB  - National GP demographic data demonstrate an increasing 'feminisation' of the
      workforce. With female GP specialty trainees continuing to outnumber males, this
      trend is set to continue. The changing composition of the workforce presents
      challenges in terms of how best to support the long-term career and educational
      development needs of this sector of the workforce in an evolving healthcare
      context. The aim of this work was to capture female GPs' experiences of working
      in general practice and their expectations concerning their career and
      educational development. Participants were surveyed and completed a semi
      structured questionnaire, which generated qualitative and quantitative data. The
      sample comprised GP registrars, principals and sessionals. This study has
      generated an important dataset on working patterns, educational experiences and
      long-term career intentions of female GPs. Despite increased representation in
      the GP workforce, female GPs (particularly those with young children) appear less
      likely to be involved in education and training than their male counterparts, and
      even less likely to be involved in roles linked to primary care trusts, medico
      political issues, hospital service delivery, special clinical interests or
      deanery education management. younger GPs reported significantly more
      difficulties in managing their childcare needs than older colleagues. Marital
      status, number of children and employment status did not moderate the effect of
      these difficulties. Female GPs reported working more hours with increasing age,
      but were not necessarily represented in a range of educational and/or training
      posts as a consequence. 

PMID- 24041097
TI  - How best to assist struggling trainees? Developing an evidence-based framework to
      guide support interventions.
AB  - OBJECTIVE: To gather rich, qualitative data on typical types and causes of
      problems faced by specialty trainees who have completed their foundation
      training, from people with experience of assisting them, as well as the different
      methods used to support individuals facing those problems. METHOD: We conducted
      interviews with 20 individuals with experience of assisting struggling GP
      trainees in the East Midlands Local Education and Training Board (12 GP trainers
      and eight employees of the Training Support Unit). Interviews were audio recorded
      and field notes were made. Content analysis was conducted on the field notes, and
      a framework was developed to summarise the data. This framework was checked for
      accuracy and comprehensiveness by 32 GP trainers who did not take part in the
      interviews. RESULTS: Our analysis identified four general categories of
      difficulties faced by trainees: (a) clinical skills and knowledge; (b)
      performance in exams or assessments; (c) effectiveness of consultations; and (d)
      engagement in training. Each of these categories contained between one and four
      types of specific difficulties faced by trainees. Up to three current sources of
      support were identified for each category including support from trainers,
      support from coaching, and other interventions. CONCLUSIONS: Key mechanisms
      identified for assisting struggling trainees all involve increasing trainees'
      awareness of gaps in their knowledge and ways of communicating. These included
      timely and accurate feedback delivered sensitively, potentially from multiple
      sources. Once GP specialty trainees are aware of their learning needs they can
      then engage with further support from the local education and training board
      (LETB) and external specialists. Therefore, LETBs should consider the support
      they are able to give trainers to facilitate their work with trainees in
      difficulty.

PMID- 24041098
TI  - What educational resources are medical students using for personal study during
      primary care attachments?
AB  - INTRODUCTION: Today's medical students have grown up in a technological world,
      with access to a wide variety of educational resources for their personal study.
      Although there is some evidence from the USA that students prefer the internet to
      textbooks, there is little evidence of UK students' preferences, particularly
      during their primary care attachments. AIMS: To identify what educational
      resources medical students are using for their personal study during primary care
      attachments and why they make these choices. METHODS: We held two focus groups,
      one with five, and one with seven fifth-year UK medical students after their
      primary care attachment. We analysed the transcripts using thematic analysis to
      identify the educational resources used, and identified themes to describe why
      the students made these choices. RESULTS: Textbooks remain students' resource of
      choice for personal study. The most popular textbook was The Oxford Handbook of
      Clinical Medicine and internet sites were Google and GP Notebook. The choice of
      resource was influenced by convenience, purpose, recommendation, exam focus,
      reliability and learning styles. Two further overarching themes influencing their
      choices were the broad nature of general practice and the use of GP tutors as an
      important learning resource. DISCUSSION: In contrast to the USA, textbooks remain
      the most popular resource for these UK students. Students felt that the style of
      learning within general practice was fundamentally different to other
      specialities due to the breadth of the subject matter and this influenced the
      resources used. This research could help inform the development of educational
      resources tailored to the learners, and provides further evidence for the need to
      develop a more structured curriculum for students in primary care. Further
      research could explore the ideal role of GP tutors.

PMID- 24041099
TI  - Professional learning during the transition from trainee to newly qualified
      general practitioner.
AB  - BACKGROUND: The transition from training to qualified practice is inherently
      challenging. Structured support following training was once available, but this
      no longer exists and the current climate of primary care places increasing
      demands on GPs. Professional learning, and the transition to independent
      practice, may thus be problematic. AIM: To explore newly qualified GPs'
      experiences of professional learning following transition into qualified
      practice. DESIGN AND SETTING: Qualitative study using semi-structured interviews
      and a focus group, conducted between December 2010 and April 2011. Participants
      were GPs within five years of qualification, working in the East of England.
      METHOD: Interviews were conducted with nine participants. These were followed by
      a focus group with four additional participants. Data collection, transcription
      and analysis were simultaneous, allowing iterative evolution of the topic guide
      to test emerging themes. RESULTS: New GPs wished to relinquish 'dependency' and
      become self-directed learners, yet still wanted guidance when needed. They
      described a situated experience of learning, in which inclusion in a practice
      community afforded greater learning opportunities. Social interactions also
      affected the issue of constructing an independent professional identity; a
      transitional process through which new GPs could become self-aware 'experts' with
      confidence in self-directed learning. CONCLUSION: Potential harms of the
      transitional period may be mitigated by support, which needs to emphasise
      inclusion, validation, affirmation and the provision of feedback. Preferences for
      adult learning should be encouraged, but guidance needs to be available when
      requested. Recent proposals for enhanced GP training introduce an opportunity for
      a focus on independent practice during training.

PMID- 24041100
TI  - GP speciality trainees' knowledge, attitude and practice regarding risks
      associated with common radiological investigations.
AB  - BACKGROUND: Thirty-eight million radiological or radio-diagnostic tests were
      undertaken in England between August 2010 and August 2011. A systematic review of
      studies based in secondary care reports that risk is rarely discussed with
      patients undergoing radiological investigations and only a minority of hospital
      doctors are well informed about the dose and risk associated with common
      radiological procedures. There is little available evidence on knowledge,
      attitudes and practice of radiological risk in a primary care setting.
      OBJECTIVES: Explore knowledge, attitudes and practice of discussing risks
      associated with common radiological procedures amongst current general practice
      specialty trainees (GPSTs). METHOD:  DESIGN: cross-sectional questionnaire-based
      survey. SETTING: GPSTs in Wales. OUTCOMES MEASURED: trainees' current knowledge,
      attitude and practice with regard to risk communication about radiological
      procedures. Participants estimated the radiation dose of common radiological
      investigations, using a chest X-ray as one unit. Participants were also asked to
      estimate the lifetime cancer risk associated with common radiological procedures.
      RESULTS: One hundred and twenty-eight completed questionnaires were returned
      (response rate 32%). Only 28% of respondents had prior radiation training.
      Although most respondents felt it was the referrer's role to explain the risk of
      radiological procedures (85%), the vast majority underestimated the radiation
      doses associated with commonly requested investigations, including lumbar and
      thoracic spine X-rays. CONCLUSION: General practice specialty trainees
      underestimate the risk of common radiological procedures. Educational
      interventions are needed to address this issue, particularly in light of
      increasing open access to radiology in primary care.

PMID- 24041101
TI  - GP trainers' experience of managing a trainee in difficulty: a qualitative study.
AB  - BACKGROUND: There is increased awareness of the consequences of poor performance
      amongst healthcare professionals on patient care. Understanding the experiences
      and needs of GP trainers involved in the management of trainees in difficulty
      (TiDs) is important in ensuring a successful outcome for trainer, learner, and
      patient care. However, there is a paucity of empirical data in this area. AIM:
      The aim of this study was to explore the perceived responses of GP trainers
      involved in the management of TiDs. We also sought to explore the strategies that
      GP trainers used in managing these responses, and the support they accessed.
      DESIGN AND SETTING: Semi-structured interviews were conducted with a purposive
      sample of 11 GP trainers involved in educational supervision of a TiD in London.
      METHODS: Semi-structured face-to-face interviews were undertaken. These were
      recorded, and transcribed verbatim. Data were handled using NVivo. Thematic
      analysis was undertaken by a team of clinical educators. RESULTS: GP trainers
      managing TiDs expressed significant anxiety as a result of concerns about patient
      safety, frustration at the lack of progress made by TiDs, and being seen as a
      failing trainer. GP trainers described the impact that TiDs had on themselves,
      their patients, practices, and on the trainer-trainee relationship as well as the
      strategies they used to manage these impacts. GP trainers used well-honed skills
      for identifying their own emotions, reflection and support (from peers and
      trainers' workshops) to manage these emotions, and steer the trainer-trainee
      relationship in a constructive direction. CONCLUSION: This study is one of the
      first to explore the impact on GP trainers of managing a TiD. It highlights the
      challenges faced and strategies used by GP trainers in helping TiDs. The use of
      experiential and peer-learning strategies is an important part of the approach
      for GP trainers in supporting TiDs as well as managing their own emotions.
      Providers of medical education need to ensure that trainers are adequately
      supported in managing such trainees.

PMID- 24041102
TI  - Failure to secure a training post in an applicant's first-choice deanery: a
      significant risk factor for difficulties during training.

PMID- 24041103
TI  - Teaching tips.

PMID- 24041104
TI  - Practice balance wheels: an aid to discussion about how practice teams function.

PMID- 24041105
TI  - International exchange of experienced GP trainers: the added value of looking
      into another kitchen.

PMID- 24041106
TI  - Other times, other places: out of programme experience (OOPE) during GP specialty
      training--a preliminary report.

PMID- 24041107
TI  - How to ... assess reflective practice.

PMID- 24041109
TI  - Evaluation of IScore validity in a Greek cohort of patients with type 2 diabetes.
AB  - BACKGROUND: Diabetes constitutes a risk factor for stroke that also aggravates
      stroke prognosis. Several prognostic models have been developed for the
      evaluation of neurologic status, severity, short-term functional outcome and
      mortality of stroke patients. IScore is a novel tool recently developed in order
      to predict mortality rates within 30 days and 1 year after ischemic stroke and
      diabetes is not included in the scoring scale of IScore. The aim of the present
      study was to evaluate and compare IScore validity in ischemic stroke patients
      with and without diabetes. METHODS: This prospective study included 312
      consecutive Caucasian patients with type 2 diabetes and 222 Caucasian patients
      without diabetes admitted for ischemic stroke in a tertiary Greek hospital.
      Thirty-day and 1-year IScores were individually calculated for each patient and
      actual mortality was monitored at the same time intervals. IScore's predictive
      ability and calibration was evaluated and compared for ischemic stroke patients
      with and without diabetes. The performance of IScore for predicting 30 and 1-year
      mortality between patients with and without diabetes was assessed by determining
      the calibration and discrimination of the score. The area under the receiver
      operating characteristic curve was used to evaluate the discriminative ability of
      IScore for patients with and without diabetes, whereas the calibration of IScore
      was assessed by the Hosmer-Lemeshow goodness-of fit statistic. RESULTS: Baseline
      population characteristics and mortality rates did not differ significantly for
      both cohorts. IScore values were significantly higher for patients with diabetes
      at 30 days and 1 year after ischemic stroke and patients with diabetes presented
      more frequently with lacunar strokes. Based on ROC curves analysis IScore's
      predictive ability for 30 day mortality was excellent, without statistically
      significant difference, for both cohorts. Predictive ability for 1 year mortality
      was also excellent for both groups with significantly better ability for patients
      with diabetes especially at high score values. Calibration of the model was good
      for both groups of patients. CONCLUSIONS: IScore accurately predicts mortality in
      acute ischemic stroke Caucasian patients with and without diabetes with higher
      efficacy in predicting 1 year mortality in patients with diabetes especially with
      high scores.

PMID- 24041110
TI  - Acupuncture in post-date pregnancy: a pilot study.
AB  - AIM: Pharmacological labor induction is obtained through intracervical/vaginal
      prostaglandins and/or oxytocin infusion; however, the use of these agents
      produces fetal and maternal side effects. Traditional Chinese medicine advocates
      the use of acupuncture to soften the cervix and induce uterine contractions. The
      aim of the present study is to investigate the effect of acupuncture to induce
      labor. Acupuncture was applied in post-date pregnancies one week before a planned
      induction; the primary outcome was the rate of women submitted to labor induction
      for prolonged pregnancy at week 41 + 5. METHODS: After informed consent, 221
      undelivered women ranging between 40 + 2/40 + 6 gestational age were considered
      eligible for the study and 202 were randomized to receive acupuncture or
      observation. Sessions of acupuncture were planned every odd day from the
      randomization till 41a week plus 4 days. At 41 + 5 week a pharmacological
      induction of labor was planned. RESULTS: The total rate of labor induction did
      not significantly differ between observation and acupuncture group (20% versus
      17%). Moreover no differences were found as far as the indications to induce
      labor, in particular "prolonged pregnancy" was similar between groups (8/96
      versus 5/99). To investigate between-group differences in time elapsed between
      inclusion and delivery, survival analysis was performed excluding women requiring
      labor induction: women receiving acupuncture showed a trend to deliver earlier
      than women in the observation group (p < 0.09). CONCLUSION: The present study
      demonstrated that acupuncture applied every odd day for one week seems
      ineffective in reducing the rate of labor induction performed for prolonged
      pregnancy at 41 + 5 weeks. Previous reports reached similar conclusions,
      independently of the different timing, duration and mode of stimuli application.

PMID- 24041111
TI  - Potential synergy between tau aggregation inhibitors and tau chaperone
      modulators.
AB  - Tau is a soluble, microtubule-associated protein known to aberrantly form amyloid
      positive aggregates. This pathology is characteristic for more than 15
      neuropathies, the most common of which is Alzheimer's disease. Finding
      therapeutics to reverse or remove this non-native tau state is of great interest;
      however, at this time only one drug is entering phase III clinical trials for
      treating tauopathies. Generally, tau manipulation by therapeutics can either
      directly or indirectly alter tau aggregation and stability. Drugs that bind and
      change the conformation of tau itself are largely classified as aggregation
      inhibitors, while drugs that alter the activity of a tau-effector protein fall
      into several categories, such as kinase inhibitors, microtubule stabilizers, or
      chaperone modulators. Chaperone inhibitors that have proven effective in tau
      models include heat shock protein 90 inhibitors, heat shock protein 70 inhibitors
      and activators, as well as inducers of heat shock proteins. While many of these
      compounds can alter tau levels and/or aggregation states, it is possible that
      combining these approaches may produce the most optimal outcome. However, because
      many of these compounds have multiple off-target effects or poor blood-brain
      barrier permeability, the development of this synergistic therapeutic strategy
      presents significant challenges. This review will summarize many of the drugs
      that have been identified to alter tau biology, with special focus on
      therapeutics that prevent tau aggregation and regulate chaperone-mediated
      clearance of tau. 

PMID- 24041112
TI  - Long-term follow up in patients with gastroesophageal reflux disease with
      specific emphasis on reflux symptoms, use of anti-reflux medication and anti
      reflux surgery outcome: a retrospective study.
AB  - BACKGROUND: Various treatment modalities are currently being used in patients
      with gastroesophageal reflux disease (GERD); however, long-term outcome is not
      clear. The aim is to evaluate long-term results of GERD treatments with regard to
      reflux symptoms, use of anti-reflux medication and anti-reflux surgery outcome.
      METHODS: Patients who had undergone 24-h pH monitoring for reflux symptoms
      between January 2002 and March 2012 were invited to fill out the Reflux Disease
      Questionnaire (RDQ) and a general questionnaire. Patients with and without anti
      reflux surgery were compared using multiple linear and logistic regression
      models. RESULTS: In total, 1027 of 2190 included patients (47%) returned the
      questionnaires. After exclusion due to predefined criteria, 477 patients were
      analyzed. Median total RDQ score was 18 points (10.2% symptom-free) in the
      conservative group (n = 304) and 10 points (31.2% symptom-free) in the surgical
      group (n = 173) after a mean follow up of 5.1 years. Daily proton pomp inhibitor
      (PPI) use was higher in the conservative group than in the surgical group (80.9%
      vs. 51.4%, p = 0.000). Linear regression analysis showed an association between
      RDQ scores and anti-reflux surgery (beta = -5.477, p = 0.001) and male gender
      (beta = -4.306, p = 0.006). Logistic regression analyses showed that daily PPI
      use was lower in patients who underwent anti-reflux surgery (odds ratio [OR] =
      0.24, p = 0.000), while it increased with age (OR = 1.03, p = 0.000).
      CONCLUSIONS: There is still a high prevalence of typical reflux symptoms and
      daily PPI use in GERD patients after >5 years of follow up. Male patients and
      patients who had undergone anti-reflux surgery were more often asymptomatic.
      Daily PPI use was lower after anti-reflux surgery, while it increased with age.

PMID- 24041113
TI  - Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate
      and elicit durable immune responses in rhesus macaques.
AB  - BACKGROUND: Live attenuated viruses are among our most potent and effective
      vaccines. For human immunodeficiency virus, however, a live attenuated strain
      could present substantial safety concerns. We have used the live attenuated
      rubella vaccine strain RA27/3 as a vector to express SIV and HIV vaccine antigens
      because its safety and immunogenicity have been demonstrated in millions of
      children. One dose protects for life against rubella infection. In previous
      studies, rubella vectors replicated to high titers in cell culture while stably
      expressing SIV and HIV antigens. Their viability in vivo, however, as well as
      immunogenicity and antibody persistence, were unknown. RESULTS: This paper
      reports the first successful trial of rubella vectors in rhesus macaques, in
      combination with DNA vaccines in a prime and boost strategy. The vectors grew
      robustly in vivo, and the protein inserts were highly immunogenic. Antibody
      titers elicited by the SIV Gag vector were greater than or equal to those
      elicited by natural SIV infection. The antibodies were long lasting, and they
      were boosted by a second dose of replication-competent rubella vectors given six
      months later, indicating the induction of memory B cells. CONCLUSIONS: Rubella
      vectors can serve as a vaccine platform for safe delivery and expression of SIV
      and HIV antigens. By presenting these antigens in the context of an acute
      infection, at a high level and for a prolonged duration, these vectors can
      stimulate a strong and persistent immune response, including maturation of memory
      B cells. Rhesus macaques will provide an ideal animal model for demonstrating
      immunogenicity of novel vectors and protection against SIV or SHIV challenge.

PMID- 24041114
TI  - A comparison of the chemical reactivity of naringenin calculated with the M06
      family of density functionals.
AB  - BACKGROUND: Chemicals generically referred to as flavonoids belong to the group
      of phenolic compounds and constitute an important group of secondary metabolites
      due to their applications as well as their biochemical properties. Flavonoids,
      which share a common benzo- gamma-pyrone structure, constitute a kind of compound
      which are highly ubiquitous in the plant kingdom. FINDINGS: The M06 family of
      density functionals has been assessed for the calculation of the molecular
      structure and properties of the Naringenin flavonoid. The chemical reactivity
      descriptors have been calculated through Conceptual DFT. The active sites for
      nucleophilic and electrophilic attacks have been chosen by relating them to the
      Fukui function indices and the dual descriptor f(2)(r). A comparison between the
      descriptors calculated through vertical energy values and those arising from the
      Koopmans' theorem approximation have been performed in order to check for the
      validity of the last procedure. CONCLUSIONS: The M06 family of density
      functionals (M06, M06L, M06-2X and M06-HF) used in the present work leads to the
      same qualitatively and quantitatively similar description of the chemistry and
      reactivity of the Naringenin molecule, yielding reasonable results. However, for
      the case of the M06-2X and M06-HF density functionals, which include a large
      portion of HF exchange, the calculations considering the validity of the
      Koopmans' theorem lead to negative electron affinities.

PMID- 24041115
TI  - Intermolecular binding modes in a novel [1 + 1] condensation 1H-pyrazole
      azamacrocycle: a solution and solid state study with evidence for CO2 fixation.
AB  - The synthesis of a novel cyclophane (L1) consisting of a 1H-pyrazole moiety
      linked through methylene groups to a 1,5,9,13-tetraazadecane chain is described.
      As far as we know, this is one of the first reported syntheses of a [1 + 1]
      condensation 1H-pyrazole azamacrocyclic ligand. The crystal structures of the
      complexes [Cu2(H(H(-1)L1))(H(-1)L1)](ClO4)3.3.75H2O (1) and ([Cu2(H(H(
      1)L1))(0.5)(H(-1)L1)(1.5)]2(ClO4)3Br2.4.2H2O (2) show that Cu(2+) coordination
      leads to formation of 2:2 Cu(2+):L dinuclear dimeric complexes in which the 1H
      pyrazole units lose a proton behaving as bis(monodentate) bridging ligands.
      Unlike previously reported complexes of [2 + 2] pyrazole azamacrocycles, the
      pyrazolate units in 1 are pointing outward from the macrocyclic cavity to bind
      the Cu(2+) ions. Inner coordination with formation of 1:1 Cu(2+):L complexes is
      however observed in [1 + 1] pyridine azamacrocycles as shown by the crystal
      structure here presented of the complex [CuL2](ClO4)2 (3). Crystals of [Cu3(H(
      1)L1)2(CO3)(H2O)](ClO4)2.8H2O (4) grown by evaporating aqueous solution at pH 9
      containing Cu(2+) and L1 in 3:2 molar ratio show the presence of a further Cu(2+)
      coordinated to the two free amine groups found in structures 1 and 2. The metal
      ion fills its coordination sphere capturing atmospheric CO2 as a eta(1),eta(2)
      bidentate carbonate anion placed in the equatorial position and an axial water
      molecule. pH-metric data, UV-vis spectroscopic data, EPR measurements, and HR-ESI
      MS data support that the outer coordination mode with formation of 2:2 dinuclear
      dimeric and 3:2 trinuclear complexes is preserved in aqueous solution.

PMID- 24041116
TI  - Dietary intake measurement using 7 d diet diaries in British men and women in the
      European Prospective Investigation into Cancer-Norfolk study: a focus on
      methodological issues.
AB  - The aim of the present study was to describe the energy, nutrient and crude v.
      disaggregated food intake measured using 7 d diet diaries (7dDD) for the full
      baseline Norfolk cohort recruited for the European Prospective Investigation into
      Cancer (EPIC-Norfolk) study, with emphasis on methodological issues. The first
      data collection took place between 1993 and 1998 in Norfolk, East Anglia (UK). Of
      the 30,445 men and women, aged 40-79 years, registered with a general
      practitioner invited to participate in the study, 25,639 came for a health
      examination and were asked to complete a 7dDD. Data from diaries with data
      recorded for at least 1 d were obtained for 99% members of the cohort; 10,354
      (89.8%) of the men and 12,779 (91.5%) of the women completed the diet diaries for
      all 7 d. Mean energy intake (EI) was 9.44 (SD 2.22) MJ/d and 7.15 (SD 1.66) MJ/d,
      respectively. EI remained approximately stable across the days, but there was
      apparent under-reporting among the participants, especially among those with BMI
      >25 kg/m2. Micronutrient density was higher among women than among men. In
      conclusion, under-reporting is an issue, but not more so than that found in
      national surveys. How foods were grouped (crude or disaggregated) made a
      difference to the estimates obtained, and comparison of intakes showed wide
      limits of agreement. The choice of variables influences estimates obtained from
      the food group data; while this may not alter the ranking of individuals within
      studies, this issue may be relevant when comparing absolute food intakes between
      studies.

PMID- 24041117
TI  - Does introduction of a Patient Data Management System (PDMS) improve the
      financial situation of an intensive care unit?
AB  - BACKGROUND: Patient Data Management Systems (PDMS) support clinical documentation
      at the bedside and have demonstrated effects on completeness of patient charting
      and the time spent on documentation. These systems are costly and raise the
      question if such a major investment pays off. We tried to answer the following
      questions: How do costs and revenues of an intensive care unit develop before and
      after introduction of a PDMS? Can higher revenues be obtained with improved PDMS
      documentation? Can we present cost savings attributable to the PDMS? METHODS:
      Retrospective analysis of cost and reimbursement data of a 25 bed Intensive Care
      Unit at a German University Hospital, three years before (2004-2006) and three
      years after (2007-2009) PDMS implementation. RESULTS: Costs and revenues
      increased continuously over the years. The profit of the investigated ICU was
      fluctuating over the years and seemingly depending on other factors as well. We
      found a small increase in profit in the year after the introduction of the PDMS,
      but not in the following years. Profit per case peaked at 1039 ? in 2007, but
      dropped subsequently to 639 ? per case. We found no clear evidence for cost
      savings after the PDMS introduction. Our cautious calculation did not consider
      additional labour costs for IT staff needed for system maintenance. CONCLUSIONS:
      The introduction of a PDMS has probably minimal or no effect on reimbursement. In
      our case the observed increase in profit was too small to amortize the total
      investment for PDMS implementation.This may add some counterweight to the
      literature, where expectations for tools such as the PDMS can be quite
      unreasonable.

PMID- 24041118
TI  - Mechanical versus clinical data combination in selection and admissions
      decisions: a meta-analysis.
AB  - In employee selection and academic admission decisions, holistic (clinical) data
      combination methods continue to be relied upon and preferred by practitioners in
      our field. This meta-analysis examined and compared the relative predictive power
      of mechanical methods versus holistic methods in predicting multiple work
      (advancement, supervisory ratings of performance, and training performance) and
      academic (grade point average) criteria. There was consistent and substantial
      loss of validity when data were combined holistically-even by experts who are
      knowledgeable about the jobs and organizations in question-across multiple
      criteria in work and academic settings. In predicting job performance, the
      difference between the validity of mechanical and holistic data combination
      methods translated into an improvement in prediction of more than 50%.
      Implications for evidence-based practice are discussed.

PMID- 24041119
TI  - Speaking more broadly: an examination of the nature, antecedents, and
      consequences of an expanded set of employee voice behaviors.
AB  - Scholarly interest in employee voice behavior has increased dramatically over the
      past 15 years. Although this research has produced valuable knowledge, it has
      focused almost exclusively on voice as a positively intended challenge to the
      status quo, even though some scholars have argued that it need not challenge the
      status quo or be well intentioned. Thus, in this paper, we create an expanded
      view of voice; one that extends beyond voice as a positively intended challenge
      to the status quo to include voice that supports how things are being done in
      organizations as well as voice that may not be well intentioned. We construct a
      framework based on this expanded view that identifies 4 different types of voice
      behavior (supportive, constructive, defensive, and destructive). We then develop
      and validate survey measures for each of these. Evidence from 5 studies across 4
      samples provides strong support for our new measures in that (a) a 4-factor
      confirmatory factor analysis model fit the data significantly better than 1-, 2-,
      or 3-factor models; (b) the voice measures converged with and yet remained
      distinct from conceptually related comparison constructs; (c) personality
      predictors exhibited unique patterns of relationships with the different types of
      voice; (d) variations in actual voice behaviors had a direct causal impact on
      responses to the survey items; and (e) each type of voice significantly impacted
      important outcomes for voicing employees (e.g., likelihood of relying on a
      voicing employee's opinions and evaluations of a voicing employee's overall
      performance). Implications of our findings are discussed.

PMID- 24041120
TI  - Guilty and helpful: an emotion-based reparatory model of voluntary work behavior.
AB  - This study proposes a dynamic reparatory model of voluntary work behavior. We
      test the hypothesis that when people are made aware of their high level of
      negative behavior at work (i.e., counterproductive work behavior) and are
      informed that their behavior is counternormative and undesirable, the knowledge
      that they violated social norms induces guilt. This guilt, in turn, results in
      compensatory behavior that is positive in nature (i.e., organizational
      citizenship behavior). We report results from a field experiment involving
      normative feedback about employees' counterproductive work behavior to support
      this model. The findings indicate that undesirable behaviors in the workplace can
      be redressed by making employees aware of the negative consequences of these
      behaviors.

PMID- 24041121
TI  - Practice effects and longitudinal cognitive change in normal aging vs. incident
      mild cognitive impairment and dementia in the Mayo Clinic Study of Aging.
AB  - The objective of this study was to examine practice effects and longitudinal
      cognitive change in a population-based cohort classified as clinically normal at
      their initial evaluation. We examined 1390 individuals with a median age of 78.1
      years and re-evaluated them up to four times at approximate 15-month intervals,
      with an average follow-up time of 5 years. Of the 1390 participants, 947 (69%)
      individuals remained cognitively normal, 397 (29%) progressed to mild cognitive
      impairment (MCI), and 46 (3%) to dementia. The stable normal group showed an
      initial practice effect in all domains which was sustained in memory and
      visuospatial reasoning. There was only a slight decline in attention and language
      after visit 3. We combined individuals with incident MCI and dementia to form one
      group representing those who declined. The incident MCI/dementia group showed an
      unexpected practice effect in memory from baseline to visit 2, with a significant
      decline thereafter. This group did not demonstrate practice effects in any other
      domain and showed a downward trajectory in all domains at each evaluation.
      Modeling cognitive change in an epidemiologic sample may serve as a useful
      benchmark for evaluating cognitive change in future intervention studies. 

PMID- 24041122
TI  - Balancing cationic and hydrophobic content of PEGylated siRNA polyplexes enhances
      endosome escape, stability, blood circulation time, and bioactivity in vivo.
AB  - A family of pH-responsive diblock polymers composed of poly[(ethylene glycol)-b
      [(2-(dimethylamino)ethyl methacrylate)-co-(butyl methacrylate)], PEG-(DMAEMA-co
      BMA), was reversible addition-fragmentation chain transfer (RAFT) synthesized
      with 0-75 mol % BMA in the second polymer block. The relative mole % of DMAEMA
      and BMA was varied in order to identify a polymer that can be used to formulate
      PEGylated, siRNA-loaded polyplex nanoparticles (NPs) with an optimized balance of
      cationic and hydrophobic content in the NP core based on siRNA packaging,
      cytocompatibility, blood circulation half-life, endosomal escape, and in vivo
      bioactivity. The polymer with 50:50 mol % of DMAEMA:BMA (polymer "50 B") in the
      RAFT-polymerized block efficiently condensed siRNA into 100 nm NPs that displayed
      pH-dependent membrane disruptive behavior finely tuned for endosomal escape. In
      vitro delivery of siRNA with polymer 50 B produced up to 94% protein-level
      knockdown of the model gene luciferase. The PEG corona of the NPs blocked
      nonspecific interactions with constituents of human whole blood, and the relative
      hydrophobicity of polymer 50 B increased NP stability in the presence of human
      serum or the polyanion heparin. When injected intravenously, 50 B NPs enhanced
      blood circulation half-life 3-fold relative to more standard PEG-DMAEMA (0 B) NPs
      (p < 0.05), due to improved stability and a reduced rate of renal clearance. The
      50 B NPs enhanced siRNA biodistribution to the liver and other organs and
      significantly increased gene silencing in the liver, kidneys, and spleen relative
      to the benchmark polymer 0 B (p < 0.05). These collective findings validate the
      functional significance of tuning the balance of cationic and hydrophobic content
      of polyplex NPs utilized for systemic siRNA delivery in vivo.

PMID- 24041123
TI  - Peripherally selective diphenyl purine antagonist of the CB1 receptor.
AB  - Antagonists of the CB1 receptor can be useful in the treatment of several
      important disorders. However, to date, the only clinically approved CB1 receptor
      antagonist, rimonabant, was withdrawn because of adverse central nervous system
      (CNS)-related side effects. Since rimonabant's withdrawal, several groups are
      pursuing peripherally selective CB1 antagonists. These compounds are expected to
      be devoid of undesirable CNS-related effects but maintain efficacy through
      antagonism of peripherally expressed CB1 receptors. Reported here are our latest
      results toward the development of a peripherally selective analog of the diphenyl
      purine CB1 antagonist otenabant 1. Compound 9 (N-{1-[8-(2-chlorophenyl)-9-(4
      chlorophenyl)-9H-purin-6-yl]piperidin-4-yl}pentanamide) is a potent, orally
      absorbed antagonist of the CB1 receptor that is >50-fold selective for CB1 over
      CB2, highly selective for the periphery in a rodent model, and without efficacy
      in a series of in vivo assays designed to evaluate its ability to mitigate the
      central effects of Delta(9)-tetrahydrocannabinol through the CB1 receptor.

PMID- 24041124
TI  - Pyrogallol[4]arenes as frustrated organic solids.
AB  - Two forms of interdigitated layered arrangements of C-pentylpyrogallol[4]arene
      (PgC5) have been structurally elucidated and show variations in packing
      arrangements and host-guest interactions. Molecular dynamics simulations reveal a
      propensity for formation of self-included dimers, with or without incorporated
      solvent. Combined gas sorption and PXRD results show the presence of seven forms
      of PgC5, with and without CO2 (and their interconversions). This is the first CO2
      gas sorption study of pyrogallol[4]arenes, and it provides evidence that
      pyrogallol[4]arenes may act as frustrated organic solids. 

PMID- 24041129
TI  - Highly efficient and robust Au/MgCuCr2O4 catalyst for gas-phase oxidation of
      ethanol to acetaldehyde.
AB  - Gold nanoparticles (AuNPs) supported on MgCuCr2O4-spinel are highly active and
      selective for the aerobic oxidation of ethanol to acetaldehyde (conversion 100%;
      yield ~95%). The catalyst is stable for at least 500 h. The unprecedented
      catalytic performance is due to strong synergy between metallic AuNPs and surface
      Cu(+) species. X-ray photoelectron spectroscopy shows that Cu(+) is already
      formed during catalyst preparation and becomes more dominant at the surface
      during ethanol oxidation. These Cu(+) species are stabilized at the surface of
      the ternary MgCuCr2O4-spinel support. Further kinetic measurements indicate that
      the Cu(+) species act as sites for O2 activation. 

PMID- 24041130
TI  - Race, coping strategies, and substance use behaviors: a preliminary analysis
      examining white and American Indian adolescents.
AB  - The association between stress exposure and substance use has been the subject of
      numerous studies. However, no prior study has explored the role of coping
      strategies in moderating the stress-substance use association for American Indian
      adolescents. Our preliminary study of coping strategies and substance use among a
      sample (n = 568) of rural American Indian and white adolescents revealed a number
      of similarities across both groups, but also some important differences. Results
      of logistic regression analyses revealed that the relationship between an
      avoidant coping strategy and marijuana use differed for whites and American
      Indians. Study limitations and future research directions are discussed. 

PMID- 24041131
TI  - "This is not who I want to be:" experiences of opioid-dependent youth before, and
      during, combined buprenorphine and behavioral treatment.
AB  - Novel, qualitative data were collected from youth in treatment for opioid
      dependence (2009-2010) regarding their experiences with opioid dependence and
      combined behavioral-pharmacological treatment. Urban youth participants were
      recruited from a larger randomized controlled trial examining the relative
      efficacy of two tapers of buprenorphine-naloxone, combined with behavioral
      treatment (ages 13-24 eligible). Twenty-two youth participated in 1- to 1.5-hour
      semi-structured interviews. A grounded theory approach guided the analysis. The
      results have the potential to inform the development of efficacious treatments
      for this growing, yet understudied, group of youth. Study implications and
      limitations are noted, and future research is prescribed.

PMID- 24041132
TI  - Smokers' knowledge about smoking-related health problems in Lebanon.
AB  - The relationship between smokers' knowledge about smoking related health problems
      and the motivation to quit smoking in a sample of Lebanese smokers was evaluated.
      The first group of smokers was composed of hospitalized subjects for a
      cardiologic or a respiratory health problem (n = 42). The second group was
      composed of smokers who have not suffered from any smoking-related health problem
      (n = 69). A positive correlation was found between the Richmond test score and
      the knowledge level about smoking related health problems (r = .302; p = .0013). 

PMID- 24041133
TI  - Tuning the electronic structure of tin sulfides grown by atomic layer deposition.
AB  - In this study, tin sulfide thin films were obtained by atomic layer deposition
      (ALD) using Tetrakis(dimethylamino)tin (TDMASn, [(CH3)2N]4Sn) and hydrogen
      sulfide (H2S). The growth rate of the tin sulfides (SnSx) was shown to be highly
      dependent on the deposition temperature, and reaction times of 1 second for the
      TDMASn and H2S were required to reach the saturation regime. Surface morphologies
      were smooth or rectangular with rounded corners as observed by a field emission
      scanning electron microscope (FE-SEM) and were dependent on temperature. X-ray
      diffraction results confirmed that the crystal structure of SnSx can be tuned by
      changing the ALD temperature. Below 120  degrees C, SnSx films appeared to be
      amorphous. In addition, SnSx films were SnS2 hexagonal at 140 and 150  degrees C
      and SnS orthorhombic above 160  degrees C. Similarly, the values of the optical
      band gap and binding energy showed significant differences between 150 and 160 
      degrees C. The electronic structures of SnSx were extracted by UPS and absorption
      spectroscopy, and the unsaturated Sn 3d molecular orbital (MO) states in the band
      edge were found to be responsible for the great improvement in electrical
      conductivity. This study shows that TDMASn-H2S ALD is an effective deposition
      method for SnSx films, offering a simple approach to tune the physical
      properties. 

PMID- 24041134
TI  - A novel noninvasive index for nonalcoholic steatohepatitis: a pilot study.
AB  - OBJECTIVE: The potential development of a noninvasive marker predicting
      nonalcoholic steatohepatitis (NASH). METHODS: Thirty patients with biopsy-proven
      nonalcoholic fatty liver disease were evaluated by numerous anthropometric,
      clinical and biochemical parameters. RESULTS: Serum glutamic oxaloacetic
      transaminase (SGOT; p = 0.027), log (erythrocyte sedimentation rate) (ESR; p =
      0.034) and homocysteine (p = 0.041) were associated with NASH independently from
      gender, age and body mass index. When combined, the regression model provided
      R(2) = 0.563 (p = 0.001) and area under the ROC curve = 0.873 +/- 0.066 (p <
      0.001). CONCLUSION: This noninvasive marker, named HSENSI (acronym of
      homocysteine, SGOT, ESR, Nonalcoholic Steatohepatitis Index), consists of three
      low cost, easily measurable parameters and may accurately predict NASH.

PMID- 24041136
TI  - The Francis inquiry: a lost opportunity?

PMID- 24041135
TI  - Exploring the focus of prenatal information offered to pregnant mothers regarding
      newborn care in rural Uganda.
AB  - BACKGROUND: Neonatal death accounts for one fifth of all under-five mortality in
      Uganda. Suboptimal newborn care practices resulting from hypothermia, poor
      hygiene and delayed initiation of breastfeeding are leading predisposing factors.
      Evidence suggests focused educational prenatal care messages to mitigate these
      problems. However, there is a paucity of data on the interaction between the
      service provider and the prenatal service user. This study aims to understand the
      scope of educational information and current practices on newborn care from the
      perspectives of prenatal mothers and health workers. METHODS: A qualitative
      descriptive methodology was used. In-depth interviews were conducted with
      lactating mothers (n = 31) of babies younger than five months old across Masindi
      in western Uganda. Additional interviews with health workers (n = 17) and their
      employers or trainers (n = 5) were conducted to strengthen our findings. Data
      were audio-taped and transcribed verbatim. A thematic content analysis was
      performed using NVivo 8. RESULTS: Vertical programmes received more attention
      than education for newborn care during prenatal sessions. In addition,
      attitudinal and communication problems existed among health workers thereby
      largely ignoring the fundamental principles of patient autonomy and patient
      centred care. The current newborn care practices were largely influenced by
      relatives' cultural beliefs rather than by information provided during prenatal
      sessions. There is a variation in the training curriculum for health workers
      deployed to offer recommended prenatal and immediate newborn care in the
      different tiers of health care. CONCLUSIONS: Findings revealed serious
      deficiencies in prenatal care organisations in Masindi. Pregnant mothers remain
      inadequately prepared for childbirth and newborn care, despite their initiative
      to follow prenatal sessions. These findings call for realignment of prenatal care
      by integrating education on newborn care practices into routine antenatal care
      services and be based on principles of patient-centred care.

PMID- 24041137
TI  - NICE quality standards: improving healthcare quality in the English NHS?

PMID- 24041138
TI  - Prescription in patients with chronic heart failure and multimorbidity attended
      in primary care.
AB  - BACKGROUND: Multimorbidity and polypharmacy pose challenges to improving the
      quality of care. OBJECTIVES: To determine the association between prescription of
      recommended treatment in ambulatory patients with chronic heart failure and
      multiple comorbidities and hospitalisation events. DESIGN: A population-based
      retrospective cohort study in Catalonia (north-east Spain). PARTICIPANTS: We
      included 7173 newly registered patients with chronic heart failure (59% women;
      mean [SD] age 76.3 [10.7] years). Patients were selected from the electronic
      patient records of primary care practices and followed for three years. OUTCOME
      MEASURES: Prescription of angiotensin-converting enzyme inhibitors (ACEIs),
      angiotensin II receptor blockers (ARBs) and beta-blockers (BBs). RESULTS:
      Prescription of ACEI/ARBs in patients managed in primary care without a
      hospitalisation event during the follow-up rose from 50.8 to 83.5% for 0 and >=4
      comorbidities, respectively, and for ACEI/ARBs and BB from 13.1 to 30.6% for 0
      and >=4 comorbidities respectively. Patients with a hospitalisation event were
      treated more often (ACEI/ARBs or 1.47 [1.17 to 1.85]; ACEI/ARBs and BB or 1.41
      [1.17 to 1.69]). Comorbid conditions receiving more treatment were hypertension
      (ACEI/ARBs or 3.75 [3.33 to 4.22]; ACEI/ARBs and BB or 1.40 [1.23 to 1.59]),
      diabetes mellitus (ACEI/ARBs or 1.79 [1.57 to 2.04]; ACEI/ARBs and BB or 1.33
      [1.18 to 1.49]) and ischaemic heart disease (ACEI/ARBs or 1.25 [1.10 to 1.42];
      ACEI/ARBs and BB or 3.01 [2.68 to 3.38]). CONCLUSION: Prescription of recommended
      treatment in patients with chronic heart failure increased as the number of
      comorbidities increased. Family physicians can provide equivalent care to more
      complex patients and those less complex, according to the number of
      comorbidities.

PMID- 24041139
TI  - Effect of the availability of weight and height data on the frequency of primary
      care physicians' documented BMI, diagnoses and management of overweight and
      obesity.
AB  - BACKGROUND: Obesity and overweight diagnoses and treatment in primary care are
      very low despite the high prevalence of obesity. Insufficient data exist on
      whether a body mass index (BMI) chart reminder improves the diagnosis and
      management of obesity and overweight in primary care. METHODS: We designed and
      placed a BMI reminder stamp on progress notes from routine medical visits. We
      assessed the difference between baseline and study periods in the proportion of
      visits with documented: (1) BMI, (2) weight diagnoses, and (3) weight-management
      plan. RESULTS: Obesity and overweight prevalence were 45 and 31%, respectively.
      Physicians documented BMI in 3% (10/383) of visits at baseline compared with 5%
      (20/383) during the study period (P = 0.04). There was no difference in the
      frequency of weight diagnoses between the study periods (18 vs 19%; P = 0.7). The
      rate of documentation of weight-management strategies was 9% (vs. 10% at
      baseline, P = 0.75). CONCLUSIONS: We observed a statistically significant
      association between the BMI chart reminder and physician documentation of BMI,
      but found no association between the BMI chart reminder and documentation of
      weight diagnoses or management. Research is needed to determine the usefulness of
      these reminders or of more intensive, yet practical, interventions in promoting
      physician recognition and management of overweight and obesity.

PMID- 24041140
TI  - Exploring representations and experiences of case-management users: towards
      difficulties and solutions to leading qualitative interviews with older people
      with complex living conditions.
AB  - BACKGROUND: By matching needs to resource services, case management could be a
      useful tool for improving the care of older people with complex living
      conditions. Collecting and analysing the users' experiences represents a good way
      to evaluate the effectiveness and efficiency of a case-management service.
      However, in the literature, fieldwork is very rarely considered and the users
      included in qualitative research seem to be the most accessible. AIM: This study
      was undertaken to describe the challenges of conducting qualitative research with
      older people with complex living conditions in order to understand their
      experiences with case-management services. METHODS: Reflective analysis was
      applied to describe the process of recruiting and interviewing older people with
      complex living conditions in private homes, describing the protocol with respect
      to fieldwork chronology. The practical difficulties inherent in this type of
      study are addressed, particularly in terms of defining a sample, the procedure
      for contacting the users and conducting the interview. The users are people who
      suffer from a loss of autonomy because of cognitive impairment, severe disease
      and/or psychiatric or social problems. Notably, most of them refuse care and
      assistance. RESULTS: Reflective analysis of our protocol showed that the
      methodology and difficulties encountered constituted the first phase of data
      analysis. CONCLUSION: Understanding the experience of users of case management to
      analyse the outcomes of case-management services requires a clear methodology for
      the fieldwork.

PMID- 24041141
TI  - Improving the management of obesity in adults: a pilot of a method to identify
      important barriers to change and tailor interventions to address them.
AB  - BACKGROUND: A tailored approach to implementation can facilitate the routine use
      of best evidence, and so improve the quality of care delivered. Tailored
      implementation involves investigating the context and barriers to change before
      selecting appropriate interventions. However, there is little evidence on the
      methods of tailoring. This study investigated the tailoring undertaken by two
      implementation groups as part of a study to improve adherence to NICE guidelines
      on adult obesity in primary care. METHODS: Data were collected from interviews
      with healthcare professionals and patients on barriers and enablers to
      implementing NICE guidelines on adult obesity along with practice performance
      data on body mass index (BMI) recording and use of interventions for obesity.
      Findings were presented to medical practitioners, university and NHS staff (n =
      12) who formed two implementation groups to independently identify the most
      important barriers and enablers, and to suggest interventions to facilitate the
      implementation of the NICE guidelines. Each group had a facilitator and were
      observed by researchers whose notes were used to understand the group processes
      and assess the usefulness of this method. RESULTS: Within the time available both
      implementation groups reached consensus on the most important barriers and
      enablers and, led by those who had personal experience of managing patients with
      weight problems, made practical proposals for interventions to improve the
      implementation of the NICE guidelines. The role of the facilitator was crucial in
      ensuring barriers, enablers and interventions were all discussed and agreed upon
      in the time available. CONCLUSIONS: The facilitated implementation groups method
      succeeded in identifying appropriate and similar barriers, enablers and
      implementation interventions, which suggests some justification for this approach
      to tailoring. However, further research into methods of tailoring is required.
      Improvements to the implementation group approach may be realised by careful
      selection of group members and provision of sufficient preparation time prior to
      group discussions.

PMID- 24041142
TI  - Quality of thyroid referrals in Saskatchewan.
AB  - BACKGROUND: A thyroid nodule is a common presentation for thyroid pathology. A
      low proportion of thyroid nodules harbour malignancy and the investigation of
      these nodules should be performed in a cost-effective manner. The American
      Thyroid Association (ATA) has published guidelines which should aid physicians in
      performing the appropriate investigations. AIM: To determine the proportion of
      patients referred to thyroid surgeons in Saskatchewan with appropriate pre
      referral work-up. METHODS: Data were retrospectively collected from the charts of
      all new thyroid referrals seen between 8 June 2011 and 8 June 2012 by two thyroid
      surgeons in the Saskatoon Health Region, Saskatchewan, Canada. Main outcome
      measures were the presence of thyroid stimulating hormone (TSH) and ultrasound
      results, and the appropriateness of ultrasound report recommendations in
      referrals to thyroid surgeons. RESULTS: Recent TSH results were done and sent to
      the thyroid surgeon in 55.1% of referrals. A recent ultrasound was performed in
      92.3% of referrals. Of patients with a high or normal TSH, a radionuclide scan
      was inappropriately recommended in 11.5% of cases. CONCLUSION: There is room for
      improvement in pre-referral work-up of patients with thyroid nodules in
      Saskatchewan, in order to facilitate appropriate clinical decision making in a
      cost-effective manner.

PMID- 24041143
TI  - Leadership and management for quality.
AB  - This is the third in a series of articles about the science of quality
      improvement. Leadership and management are required for change and are therefore
      important for all quality improvement initiatives. We describe the differences
      between and features of each, and how they support change in individuals, groups
      and organisations according to the culture and characteristics of the latter.
      Finally, we see that leadership competencies are conceptualised in the NHS
      Leadership Framework and how this can be applied to quality improvement in
      general practice and healthcare more generally. 

PMID- 24041144
TI  - What factors will impact on the adoption of digital technology to access general
      practitioners in Australia?
AB  - The geography of large and relatively underpopulated countries like Australia
      makes it attractive to use increasingly cheap information technology to improve
      access to general practitioners. People are already using the internet to access
      many other services. However, there are some moderating influences on the use of
      video-consultations in general practice. These include technical limitations,
      patient confidentiality concerns, regulatory issues as well as the willingness of
      general practitioners to consult patients other than face-to-face. Theories
      predict that a relatively small cadre of innovative doctors are those most likely
      to try video-consultations for routine consultations. However, much will depend
      on research that demonstrates that video-consultations are unlikely to harm
      patients or increase the risk of litigation; on the scope to incorporate
      diagnostic equipment on home computers; on the financial incentives offered to
      doctors and on the public proclamations of opinion leaders on the question of
      video-consultations. 

PMID- 24041145
TI  - Influence of salt purity on Na+ and palmitic acid interactions.
AB  - The influence of salt purity on the interactions between Na(+) ions and the
      carboxylate (COO(-)) head group of palmitic acid (PA) monolayers is studied in
      the COO(-) and OH stretching regions using broad-band vibrational sum frequency
      generation (VSFG) spectroscopy. Ultrapure (UP) and ACS grade NaCl salts are used
      for aqueous solution preparation after proper pretreatment. The time evolution of
      VSFG spectra of PA monolayers on solutions made from these two grades of salts is
      different, which reveals that the salt purity has a significant impact on the
      interactions between Na(+) ions and the COO(-) group of PA. The trace metal
      impurities in ACS grade salt, which are more abundant than those in UP grade
      salt, are responsible for this difference due to their stronger affinity for the
      carboxylate group relative to Na(+) and further affects the interfacial water
      structure. These results suggest that the alkali salt grade even after
      pretreatment is critical in the studies of alkali cation-carboxylate interactions
      and comparison of relative binding affinities of different cations. 

PMID- 24041146
TI  - Endogenous ethanol affects biopolyester molecular weight in recombinant
      Escherichia coli.
AB  - In biopolyester synthesis, polyhydroxyalkanoate (PHA) synthase (PhaC) catalyzes
      the polymerization of PHA in bacterial cells, followed by a chain transfer (CT)
      reaction in which the PHA polymer chain is transferred from PhaC to a CT agent.
      Accordingly, the frequency of CT reaction determines PHA molecular weight.
      Previous studies have shown that exogenous alcohols are effective CT agents. This
      study aimed to clarify the effect of endogenous ethanol as a CT agent for
      poly[(R)-3-hydroxybutyrate] [P(3HB)] synthesis in recombinant Escherichia coli,
      by comparing with that of exogenous ethanol. Ethanol supplementation to the
      culture medium reduced P(3HB) molecular weights by up to 56% due to ethanol
      induced CT reaction. NMR analysis of P(3HB) polymers purified from the culture
      supplemented with (13)C-labeled ethanol showed the formation of a covalent bond
      between ethanol and P(3HB) chain at the carboxyl end. Cultivation without ethanol
      supplementation resulted in the reduction of P(3HB) molecular weight with
      increasing host-produced ethanol depending on culture aeration. On the other
      hand, production in recombinant BW25113(DeltaadhE), an alcohol dehydrogenase
      deletion strain, resulted in a 77% increase in molecular weight. Analysis of five
      E. coli strains revealed that the estimated number of CT reactions was correlated
      with ethanol production. These results demonstrate that host-produced ethanol
      acts as an equally effective CT agent as exogenous ethanol, and the control of
      ethanol production is important to regulate the PHA molecular weight. 

PMID- 24041147
TI  - Prevalence of anemia in pregnant women and its effect on neonatal outcomes in
      Northeast India.
AB  - OBJECTIVES: To determine the prevalence of anemia in pregnant women and
      characterize its effect on neonatal outcome in Northeast India. PATIENTS AND
      METHODS: Four hundred and seventy mothers and their newborn infants during a one
      month period were included. The association between maternal hemoglobin (Hb) at
      delivery and neonatal outcomes were determined. RESULTS: Anemia (Hb < 110 g/L)
      was present in 421 (89.6%) mothers with 35 (8.3%) having severe anemia(Hb < 70
      g/L). After adjusting for maternal and neonatal variables, each 10 g/L decrease
      in maternal Hb was associated with 0.18 week decrease in gestational length (p =
      0.003) and 21 g decrease in birth weight (p = 0.093). Severe maternal anemia was
      associated with 0.63 week (95% CI, 0.03-1.23week) shorter gestation, 481 g (95%
      CI, 305-658 g) lower birth weight and 89% increased risk of small-for-gestation
      (OR 1.89, 95% CI, 1.25-2.86)in the offspring, compared with those born to mothers
      without anemia (p < 0.001). CONCLUSION: Maternal anemia was highly prevalentin
      this population. Lower gestational age and birth weight, and increased risk of
      small-for-gestation were associated with maternal anemia, especially when
      maternal Hb was <80 g/L. Maternal anemia needs urgent attention to improve
      neonatal outcome in this population.

PMID- 24041148
TI  - Training nonanesthetist administration of propofol for gastrointestinal endoscopy
      in scenario-based full-scale hybrid simulation--a pilot study.
AB  - OBJECTIVE: The use of nonanesthetist-administered propofol (NAAP) in GI endoscopy
      has long been controversial. In the setting of NAAP, acute situations can develop
      during endoscopy and thus training before starting with NAAPs is considered
      crucial. The aim was to evaluate a pilot study on crew resource management (CRM)
      based training of teams of endoscopists and endoscopy nurses in NAAP in a full
      scale hybrid simulation consisting of a full-scale human patient simulator and an
      endoscopy simulator. Our hypothesis was that the training would increase the self
      efficacy of the participants. MATERIAL AND METHODS: Four scenarios were created,
      each with typical side effects of propofol administration. All scenarios included
      the need for prompt decision-making and treatment. Colonoscopy, gastroscopy or
      endoscopic retrograde cholangiopancreatography (ERCP) cases were assigned to the
      course participants in coherence with their main clinical expertise in order to
      facilitate situated and contextualized training. Twenty-one participants (ten
      doctors and eleven nurses) completed a questionnaire on self-efficacy before and
      after the course. A questionnaire regarding the quality and yield of the course
      was also completed. RESULTS: For all participants, the self-efficacy score was
      26.0 (24.0-28.0; interquartile range) before training and 30.0 (27.0-30.5) after
      training (p = 0.0003). The ten doctors had a self-efficacy score before training
      of 26.5 (25.0-29.5) and 30.0 (29.0-33.0) after (p = 0.0078). The eleven nurses
      scored 24.0 (22.0-26.0) before and 28.0 (27.0-30.0) after training (p = 0.0098).
      CONCLUSIONS: Systematic target focused scenario-based training with hybrid
      simulation of NAAP in endoscopy resulted in increased self-efficacy in both
      nurses and physicians.

PMID- 24041149
TI  - Invest in adolescents and young people: it pays.
AB  - This year's Women Deliver conference made a strong call for investing in the
      health and development of adolescents and young people. It highlighted the unique
      problems faced by adolescent girls and young women-some of the most vulnerable
      and neglected individuals in the world-and stressed the importance of addressing
      their needs and rights, not only for their individual benefit, but also to
      achieve global goals such as reducing maternal mortality and HIV infection.In
      response to an invitation from the editors of Reproductive Health, we-the sixteen
      coauthors of this commentary-put together key themes that reverberated throughout
      the conference, on the health and development needs of adolescents and young
      people, and promising solutions to meet them.1. Investing in adolescents and
      young people is crucial for ensuring health, creating prosperity and fulfilling
      human rights.2. Gender inequality contributes to many health and social problems.
      Adolescent girls and boys, and their families and communities, should be
      challenged and supported to change inequitable gender norms.- Child marriage
      utterly disempowers girls. It is one of the most devastating manifestations of
      gender discrimination.- Negative social and cultural attitudes towards
      menstruation constrain the lives of millions of girls. This may well establish
      the foundation for lifelong discomfort felt by girls about their bodies and
      reticence in seeking help when problems arise.3. Adolescents need comprehensive,
      accurate and developmentally appropriate sexuality education. This will provide
      the bedrock for attitude formation and decision making.4. Adolescent-centered
      health services can prevent sexual and reproductive health problems and detect
      and treat them if and when they occur.5. National governments have the authority
      and the responsibility to address social and cultural barriers to the provision
      of sexual and reproductive health education and services for adolescents and
      young people.6. Adolescents should be involved more meaningfully in national and
      local actions intended to meet their needs and respond to their problems.7. The
      time to act is now. We know more now than ever before about the health and
      development needs of adolescents and young people, as well as the solutions to
      meeting those needs.

PMID- 24041150
TI  - Wide-band excited Y6(WMo)(0.5)O12:Eu red phosphor for white light emitting diode:
      structure evolution, photoluminescence properties, and energy transfer mechanisms
      involved.
AB  - Y6(WMo)(0.5)O12 activated with Eu(3+) ions was investigated as a red-emitting
      conversion phosphor for white light emitting diodes (WLEDs). The phosphors were
      synthesized by calcining a citrate-complexation precursor at different
      temperatures. The photoluminescence properties of the phosphors and the energy
      transfer mechanisms involved were studied as a function of structure evolution.
      It was found that the host lattices were crystallized in a cubic or a hexagonal
      phase depending on the synthesis conditions. Although all the phosphors showed
      intensive red emission under an excitation of near-UV or blue light due to energy
      transfer from the host lattices to Eu(3+) ions, the photoluminescence spectra and
      temporal decay features were found to vary significantly with the structure and
      crystallinity of the host lattice. The mechanisms of the energy transfer from the
      host lattices to Eu(3+) ions and energy quenching among Eu(3+) ions were
      discussed on the basis of structure evolution of the host lattice. Phosphors
      calcined at 800 and 1300  degrees C were suggested to be promising candidates for
      blue and near-UV light excited WLEDs, respectively.

PMID- 24041151
TI  - Rapid destruction of the rhodamine B using TiO2 photocatalyst in the liquid phase
      plasma.
AB  - BACKGROUND: Rhodamine B (RhB) is widely used as a colorant in textiles and food
      stuffs, and is also a well-known water tracer fluorescent. It is harmful to human
      beings and animals, and causes irritation of the skin, eyes and respiratory
      tract. The carcinogenicity, reproductive and developmental toxicity,
      neurotoxicity and chronic toxicity toward humans and animals have been
      experimentally proven. RhB cannot be effectively removed by biological treatment
      due to the slow kinetics. Therefore, RhB is chosen as a model pollutant for
      liquid phase plasma (LPP) treatment in the present investigation. RESULTS: This
      paper presents experimental results for the bleaching of RhB from aqueous
      solutions in the presence of TiO2 photocatalyst with LPP system. Properties of
      generated plasma were investigated by optical emission spectroscopy methods. The
      results of electrical-discharge degradation of RhB showed that the decomposition
      rate increased with the applied voltage, pulse width, and frequency. The oxygen
      gas addition to reactant solution increases the degradation rate by active oxygen
      species. The RhB decomposition rate was shown to increase with the TiO2 particle
      dosage. CONCLUSION: This work presents the conclusions on the photocatalytic
      oxidation of RhB, as a function of plasma conditions, oxygen gas bubbling as well
      as TiO2 particle dosage. We knew that using the liquid phase plasma system with
      TiO2 photocatalyst at high speed we could remove the organic matter in the water.

PMID- 24041152
TI  - Height as an indicator of economic status in the Polish territories under Russian
      rule at the turn of the 19th to 20th century.
AB  - Height is regarded as one of the indicators of environmental stress at population
      level, being an excellent barometer of standard of living. The aim of this study
      was to describe diversity in height among populations living in different regions
      of the Kingdom of Poland in terms of the economic factors in the second half of
      the 19th and early 20th century. This study examines the height of adult
      inhabitants from five guberniyas (provinces) of the Kingdom of Poland (Lomza,
      Warsaw, Radom, Kalisz and Plock) collected in the years 1897-1914 (N = 732 men, N
      = 569 women). Differences in average height of male and female inhabitants across
      the five guberniyas were examined using ANOVA and the Fisher's LSD (Least
      Significant Difference) test of multiple comparisons. Statistically significant
      differences in the height between the guberniyas were observed. Diversity in the
      economic development in the studied guberniyas of the Kingdom of Poland
      translated into differences in the height of their inhabitants. Moreover, an
      increase in mean height over time was noted.

PMID- 24041154
TI  - Nanoprotective Layer-by-Layer coatings with epoxy components for enhancing
      abrasion resistance: toward robust multimaterial nanoscale films.
AB  - Layer-by-Layer (LbL) assembled films offer many interesting applications (e.g.,
      in the field of nanoplasmonics), but are often mechanically feeble. The
      preparation of nanoprotective films of an oligomeric novolac epoxy resin with
      poly(ethyleneimine) using covalent LbL-assembly is described. The film growth is
      linear, and the thickness increment per layer pair is easily controlled by
      varying the polymer concentration and/or the adsorption times. The abrasion
      resistance of such cross-linked films was tested using a conventional rubbing
      machine and found to be greatly enhanced in comparison to that of classic LbL
      films that are mostly assembled through electrostatic interactions. These robust
      LbL-films are then used to mechanically protect LbL-films that would completely
      be removed by a few rubbing cycles in the absence of a protective coating. A 45
      nm thick LbL-film composed of gold nanoparticles and poly(allylamine
      hydrochloride) was chosen as an especially weak example for a functional
      multilayer system. The critical thickness for the protective LbL-coatings on top
      of the weak multilayer was determined to be about 6 layer pairs corresponding to
      about only 10 nm. At this thickness, the whole film withstands at least 25
      abrasion cycles with a reduction of the total thickness of only about 2%. 

PMID- 24041153
TI  - Epidemiological strategies for adapting clinical practice guidelines to the needs
      of multimorbid patients.
AB  - BACKGROUND: Clinical practice guidelines have been developed to improve the
      quality of health care. However, adherence to current monomorbidity-focused, mono
      disciplinary guidelines may result in undesirable effects for persons with
      several comorbidities, in adverse interactions between drugs and diseases,
      conflicting management strategies, and polypharmacy. This is why new types of
      guidelines that address the problem of interacting medical interventions and
      conditions in multimorbid patients are needed. DISCUSSION: Previous research
      projects investigated patterns of multimorbidity and were able to identify
      combinations of the most prevalent chronic conditions, or clusters of
      comorbidities. These results represent potential methodological starting points
      for the development of guidelines that account for multimorbidity. The objective
      of these efforts is to identify frequent reasons for interactions and adverse
      events that may occur when the current type of guideline is rigorously applied in
      multimorbid patients. SUMMARY: The epidemiologic approaches described above may
      help guideline developers as a kind of check list of disease combinations that
      should systematically be considered during guideline development. Given the risk
      of worse outcomes in a huge group of vulnerable patients, researchers, guideline
      developers, and funding institutions should give first priority to the
      development of guidelines more appropriate for use in multimorbid persons.

PMID- 24041155
TI  - Changes in experienced value of everyday occupations after nature-based
      vocational rehabilitation.
AB  - OBJECTIVE: The aim of this study was to describe and assess changes in
      participants' experiences of everyday occupations after nature-based vocational
      rehabilitation (NBVR), to assess changes regarding symptoms of severe stress and
      the rate of return to work and possible association with experiencing the
      occupational value of everyday occupations. METHODS: The NBVR was carried out by
      a transdisciplinary rehabilitation team and took place in a specially designed
      rehabilitation garden. The study had a longitudinal and mixed-method approach.
      Data concerning experiences of everyday occupations (Oval-pd), self-assessed
      occupational competence (OSA-F), health status (EQ-VAS, SCI-93), and sense of
      coherence (SOC-13) were collected before and after the intervention, and a one
      year follow-up was carried out regarding returning to work. Semi-structured
      interviews were performed 12 weeks after the intervention. RESULTS: Significant
      changes were measured regarding perceived occupational values in daily life,
      symptoms of severe stress, and returning to work. Both the return to work rate
      and symptoms of severe stress were significantly associated with changed
      experience of everyday occupation. CONCLUSIONS: In the interviews, participants
      explained that they now had a slower pace of everyday life and that everyday
      occupations were more often related to nature and creativity. This could be
      interpreted as nature-based rehabilitation inducing changes through meaningful
      occupations in restorative environments, leading to a positive change in
      perceived values of everyday occupations.

PMID- 24041157
TI  - Unique photophysical behavior of 2,2'-bipyridine-3,3'-diol in DMSO-water binary
      mixtures: potential application for fluorescence sensing of Zn2+ based on the
      inhibition of excited-state intramolecular double proton transfer.
AB  - In this work we have investigated the anomalous behavior of DMSO-water binary
      mixtures using 2,2'-bipyridine-3,3'-diol (BP(OH)2) as a microenvironment
      sensitive excited-state-intramolecular-double-proton-transfer (ESIDPT) probe.
      Here we present results on the UV-vis absorption and fluorescence properties of
      BP(OH)2 in the binary solutions. DMSO-water binary mixtures at various
      compositions are an intriguing hydrogen bonded system, where DMSO acts to
      diminish the hydrogen bonding ability of water with the dissolved solutes. As a
      result, we observe unusual changes in the photophysical properties of BP(OH)2
      with increasing DMSO content in complete correlation with the prior simulation
      and experimental results on the solvent structures and dynamics. The fluorescence
      quantum yield and fluorescence lifetime of BP(OH)2 depend strongly on the DMSO
      content and become maximum at very low mole fraction (~0.12) of DMSO. The
      anomalous behavior at this particular region likely arises from the enhanced pair
      hydrophobicity of the medium as demonstrated by Bagchi and co-workers (Banerjee,
      S.; Roy, S.; Bagchi, B. J. Phys. Chem. B 2010, 114, 12875-12882). In addition we
      have also shown the utilization of BP(OH)2 as a potential Zn(2+)-selective
      fluorescent sensor in a 1:1 DMSO-water binary mixture useful for biological
      applications. We observed highly enhanced fluorescence emission of BP(OH)2
      selectively for binding with the Zn(2+) metal ion. Moreover, the fluorescence
      emission maximum of BP(OH)2-Zn(2+) is significantly blue-shifted with a reduced
      Stokes shift due to the inhibition of the ESIDPT process of BP(OH)2 through
      strong coordination. 

PMID- 24041156
TI  - Recent advances reveal IL-8 signaling as a potential key to targeting breast
      cancer stem cells.
AB  - Breast cancer stem-like cells (CSCs) are an important therapeutic target as they
      are purported to be responsible for tumor initiation, maintenance, metastases,
      and disease recurrence. Interleukin-8 (IL-8) is upregulated in breast cancer
      compared with normal breast tissue and is associated with poor prognosis. IL-8 is
      reported to promote breast cancer progression by increasing cell invasion,
      angiogenesis, and metastases and is upregulated in HER2-positive cancers.
      Recently, we and others have established that IL-8 via its cognate receptors,
      CXCR1 and CXCR2, is also involved in regulating breast CSC activity. Our work
      demonstrates that in metastatic breast CSCs, CXCR1/2 signals via transactivation
      of HER2. Given the importance of HER2 in breast cancer and in regulating CSC
      activity, a pathway driving the activation of these receptors would have
      important biological and clinical consequences, especially in tumors that express
      high levels of IL-8 and other CXCR1/2-activating ligands. Here, we review the IL
      8 signaling pathway and the role of HER2 in maintaining an IL-8 inflammatory loop
      and discuss the potential of combining CXCR1/2 inhibitors with other treatments
      such as HER2-targeted therapy as a novel approach to eliminate CSCs and improve
      patient survival.

PMID- 24041158
TI  - Inflammatory cytokine network in schizophrenia.
AB  - OBJECTIVES: The purpose of this review is to analyse, sum up and discuss the
      available literature on the role of inflammation and inflammatory cytokines in
      the pathogenesis of schizophrenia. METHODS: An electronic literature search of
      peer-reviewed English language articles using Pubmed was undertaken. These
      articles together with those published by us provided the background for the
      present review. RESULTS: An overview of the available literature on this issue
      clearly demonstrated the alterations in mRNA and protein expression levels of
      several proinflammatory and chemotactic cytokines in patients with schizophrenia.
      Importantly, some of these changes are genetically determined. It was noteworthy
      that, depending on the study population, some variations of the data obtained are
      detected. CONCLUSIONS: Altered inflammatory cytokine production, both genetically
      and environmentally determined, is implicated in schizophrenia and contributes to
      disease-associated low-grade systemic inflammation. Proinflammatory and
      chemotactic cytokines and their receptors may represent additional therapeutic
      targets for treatment of schizophrenia.

PMID- 24041159
TI  - Diffuse large B-cell lymphoma and mantle cell lymphoma of the ocular adnexal
      region, and lymphoma of the lacrimal gland: an investigation of clinical and
      histopathological features.
AB  - Diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) constitute
      two distinct subtypes of non-Hodgkin lymphoma (NHL) associated with considerable
      morbidity and mortality. Marked diversities with regard to molecular biology and
      clinical features are recognized in different subsets of the two lymphomas.
      Because these differences could be related to the location of the lymphoma, it is
      of interest to investigate the clinical and histopathological features of DLBCL
      and MCL involving the ocular adnexal region (i.e. the orbit, eyelids,
      conjunctiva, lacrimal gland and lacrimal sac). Similarly, the lacrimal gland is
      the only glandular structure within the orbit. Because the lacrimal gland
      represents an important part of the immunological system, it is of interest to
      investigate lymphomas involving this location with regard to clinical and
      histological characteristics. PURPOSE:   To characterize the clinical and
      histopathological features of Danish patients with DLBCL of the ocular adnexal
      region between 1980 and 2009 and of Danish ocular adnexal MCL patients from 1980
      to 2005. Furthermore, the aim of this PhD was to review all specimens from
      patients with lymphoma of the lacrimal gland in Denmark between 1975 and 2009 to
      determine the distribution of lymphoma subtypes of the lacrimal gland and to
      describe the clinicopathological features of these patients. RESULTS:   A total
      of 34 patients with DLBCL and 21 with MCL of the ocular adnexal region were
      identified. Twenty-seven patients had lacrimal gland lymphoma, including four
      DLBCLs and three MCLs from studies I and II. Elderly patients predominated in all
      three groups, with median ages of 78, 75 and 69 years in the DLBCL, the MCL and
      the lacrimal gland lymphoma groups, respectively. MCL patients had a
      preponderance of males, whereas females prevailed among lacrimal gland lymphoma
      patients. The orbit was the most common site of involvement in DLBCL and MCL.
      Most DLBCL patients had unilateral involvement, while MCL patients had a high
      frequency of bilateral involvement. Similarly, localized lymphoma was relatively
      frequently seen in DLBCL patients in contrast to the predominance of disseminated
      lymphoma in the MCL group. The majority of lacrimal gland lymphomas were low
      grade, and the distribution of subtypes was as follows: extranodal marginal zone
      lymphoma, 10 (37%); follicular lymphoma, 5 (19%); DLBCL, 4 (15%); MCL, 3 (11%);
      chronic lymphocytic leukaemia/small lymphatic lymphoma, 2 (7%); and unclassified
      B-cell lymphoma, 3 (11%). The overall survival rates at 3 and 5 years for the
      entire study group of DLBCL were 42% and 20%, whereas 58% and 22% of MCL patients
      were alive 3 and 5 years after the time of diagnosis. The 5-year overall survival
      rate of lacrimal gland lymphoma patients was 70%. Concordant bone marrow
      involvement and the International Prognostic Index score were predictive factors
      for the overall survival in the DLBCL group in Cox regression analysis. Rituximab
      containing chemotherapy was associated with an improved survival rate in MCL
      patients. CONCLUSIONS:   Diffuse large B-cell lymphoma and MCL involving the
      ocular adnexal region and lymphoma of the lacrimal gland are prevalent among
      elderly patients. The overall prognosis in DLBCL and MCL was poor, whereas the
      prognosis for lacrimal gland lymphoma patients was relatively good. Concordant
      bone marrow involvement and the International Prognostic Index score were
      independent predictive factors for mortality in the DLBCL group. Chemotherapy
      containing rituximab significantly improved survival in the MCL group.

PMID- 24041160
TI  - Time-resolved magnetic field effects distinguish loose ion pairs from exciplexes.
AB  - We describe the experimental investigation of time-resolved magnetic field
      effects in exciplex-forming organic donor-acceptor systems. In these systems, the
      photoexcited acceptor state is predominantly deactivated by bimolecular electron
      transfer reactions (yielding radical ion pairs) or by direct exciplex formation.
      The delayed fluorescence emitted by the exciplex is magnetosensitive if the
      reaction pathway involves loose radical ion pair states. This magnetic field
      effect results from the coherent interconversion between the electronic singlet
      and triplet radical ion pair states as described by the radical pair mechanism.
      By monitoring the changes in the exciplex luminescence intensity when applying
      external magnetic fields, details of the reaction mechanism can be elucidated. In
      this work we present results obtained with the fluorophore-quencher pair 9,10
      dimethylanthracene/N,N-dimethylaniline (DMA) in solvents of systematically varied
      permittivity. A simple theoretical model is introduced that allows discriminating
      the initial state of quenching, viz., the loose ion pair and the exciplex, based
      on the time-resolved magnetic field effect. The approach is validated by applying
      it to the isotopologous fluorophore-quencher pairs pyrene/DMA and pyrene-d10/DMA.
      We detect that both the exciplex and the radical ion pair are formed during the
      initial quenching stage. Upon increasing the solvent polarity, the relative
      importance of the distant electron transfer quenching increases. However, even in
      comparably polar media, the exciplex pathway remains remarkably significant. We
      discuss our results in relation to recent findings on the involvement of
      exciplexes in photoinduced electron transfer reactions. 

PMID- 24041161
TI  - Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting
      and cell death pathways.
AB  - The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of
      general formula OsN(N^N)Cl3 (N^N = 2,2'-bipyridine 1, 1,10-phenanthroline 2,
      3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4)
      can be tuned by subtle ligand modifications. Complex 2 induces DNA damage,
      resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase,
      and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic
      reticulum (ER) stress leading to the upregulation of proteins of the unfolded
      protein response pathway, increase in ER size, and p53-independent apoptotic cell
      death. To the best of our knowledge, 4 is the first osmium compound to induce ER
      stress in cancer cells. 

PMID- 24041162
TI  - Six-year integrated cardiothoracic surgery residency applicants: characteristics,
      expectations, and concerns.
AB  - OBJECTIVE: During the past 5 years, 6-year integrated cardiothoracic surgery
      residency programs have increased in number and popularity. METHODS: To
      understand the background and motivation of the applicants for 6-year integrated
      programs, we surveyed 80 candidates interviewing for Accreditation Council for
      Graduate Medical Education-accredited 6-year integrated cardiothoracic surgery
      residency programs for the 2012 match season, with 36 respondents completing the
      survey. RESULTS: The applicants interviewed for 6-year integrated programs had
      peer-reviewed publications (91.7%) and were interested in academic careers
      (91.4%), dedicated research time (58.3%), and cardiac surgery (66.7%). The time
      saved in training was considered an advantage of the 6-year integrated
      cardiothoracic surgery residency programs, although concern was present about the
      development of the mature, well-rounded cardiothoracic surgeon. CONCLUSIONS: We
      found that most of the candidates for 6-year integrated cardiothoracic surgery
      residency were young, high-achieving individuals oriented toward academic careers
      with a significant interest in dedicated research time and cardiac surgery.

PMID- 24041163
TI  - Reply to the editor.

PMID- 24041164
TI  - The dog didn't bark.

PMID- 24041165
TI  - Supplementation of n-3 polyunsaturated fatty acids to prevent postoperative
      atrial fibrillation in patients subjected to heart surgery.

PMID- 24041166
TI  - Reply to the editor.

PMID- 24041167
TI  - Response to staged percutaneous coronary intervention and minimally invasive
      valve surgery: results of a hybrid approach to concomitant coronary and valvular
      disease.

PMID- 24041168
TI  - Sutureless aortic valve replacement in the presence of a mechanical mitral
      prosthesis.

PMID- 24041169
TI  - A review of the many meanings of an unseizable concept.

PMID- 24041170
TI  - Religion is good, belief is better: religion, religiosity, and substance use
      among young Swiss men.
AB  - We examined the influence of religious denomination (RD) and
      religiosity/spirituality on licit and illicit substance use beyond the potential
      impact of parental variables. Data from a representative sample of Swiss men (n =
      5,387) approximately 20 years old were collected between August 2010 and November
      2011. We asked single item questions about RD and religious self-description
      (RSD) (including aspects of spirituality). Alcohol use, smoking, and illicit drug
      use was measured as outcome variables. Logistic regressions (adjusting for
      parenting and socioeconomic background) revealed that religiosity/spirituality
      was inversely associated with substance use and that it was more strongly
      associated than denomination. RD, particularly having no denomination, was
      independently associated with the use of most substances. The study's
      limitations, and the implications for future work are noted. 

PMID- 24041171
TI  - Unlocking the spiritual with club drugs: a case study of two youth cultures.
AB  - Researchers have become increasingly interested in the link between spirituality
      and the use and misuse of drugs as well as intervention. First, studies have
      pointed to spirituality and religious involvement as a protective factor against
      substance use. Second, the quest for spirituality can play a role in drug use.
      This article has two aims. First, it seeks to examine the features of
      spirituality connected with both recovery from drug misuse and psychoactive drug
      use. Second, it seeks to understand the latter in the context of contemporary
      youth culture. We draw from our comparative study on club drug use among young
      people in two cultural locales-San Francisco and Hong Kong, where two different
      drugs, ecstasy and ketamine, have become associated in different dance party
      settings with a spiritual awakening of self-awareness and liberation. 

PMID- 24041172
TI  - Spirituality, intoxication and addiction: six forms of relationship.
AB  - The paper considers six connections between spirituality and intoxication or
      addiction. They are: intoxication as a means of communication with a spiritual
      world; intoxication as destroying spirituality; shared use and intoxication as
      creating and validating community; spirituality and religion as a means of
      collective sobering-up; spirituality in individual sobering up; and abstinence as
      a spiritual practice, a witness, or a badge of membership in a spiritual
      community. Intoxication can either enhance or impede spirituality, both at
      individual and collective levels. Spirituality is often important in sobering up,
      both individually and collectively, and abstinence is a part of spiritual or
      religious practice in some traditions. But a full account must acknowledge the
      diversity in the interactions of spirituality and intoxication or addiction. 

PMID- 24041173
TI  - Spirituality and religion in response to substance misuse among indigenous
      Australians.
AB  - The ongoing quest for effective ways of preventing and managing alcohol and other
      drug use-related problems among Indigenous Australians has spawned a variety of
      approaches, including AA-based treatment, population health-based preventive
      approaches, and various forms of cultural healing. This paper examines two inter
      related sources of ideas and strategies: firstly, the emergence since the 1970s
      of evangelical Christianity in some Aboriginal communities as a response to
      profound changes, including increased access to alcohol. The second is the
      attempt to invoke Indigenous spirituality as an alternative to both western
      Christianity and western biomedical intervention models. We also discuss the
      representation of Australian Indigenous spirituality within New Age and related
      discourses. 

PMID- 24041174
TI  - Do religion and religiosity have anything to do with alcohol consumption
      patterns? Evidence from two fish landing sites on Lake Victoria Uganda.
AB  - Fish landing sites have high levels of harmful use of alcohol. This paper
      examines the role of religion and religiosity on alcohol consumption at two fish
      landing sites on Lake Victoria in Uganda. Questionnaires were administered to
      randomly selected people at the sites. Dependent variables included alcohol
      consumption during the previous 30 days, whereas the key independent variables
      were religion and religiosity. Bivariate and multivariate analysis techniques
      were applied. People reporting low religiosity were five times more likely to
      have consumed alcohol (95% confidence interval: 2.45-10.04) compared with those
      reporting low/average religiosity. Religion and religiosity are potential
      channels for controlling alcohol use. 

PMID- 24041175
TI  - Catholic mass and its healing implications for the addicted person.
AB  - A convenience sample of 12 recovering alcoholics/addicts were interviewed, using
      open-ended interviews, during 2009 regarding their experience of Catholic Mass in
      relation to their recovery. Half of the participants had been raised Catholic,
      whereas the other half had converted. All have participated in Alcoholics
      Anonymous and lived in various areas in California. Data analysis used a
      phenomenological method allowing for use of the participant's own vocabulary.
      Implications and study limitations are noted, as well as suggestions for further
      research. 

PMID- 24041176
TI  - The god within and the god without.
AB  - Spirituality enables the direct experience of connection between the individual
      and God, and can exist with or without an intermediary such as a religious
      institution. Via meditation or spiritual practice one can find God within
      oneself. Seeing oneself as a little Christ or Buddha affirms that one is sacred,
      and worthy of self-love and self-respect. This self-image is incongruent with
      violence to the self, such as substance misuse. Through spirituality we learn to
      see ourselves as parts of a whole, and worthy of the love and respect of others.
      This love is sustainable, and can fulfill what was unconsciously or consciously
      sought through the misuse of substances. From the point of view of the therapist,
      this is the beginning of healing. 

PMID- 24041177
TI  - Perception of the role of spirituality and religiosity in the addiction treatment
      program among the Italian health professionals: a pilot study.
AB  - In this pilot study, 69 health professionals working in public and private
      programs treating drug users and alcohol misusers in Italy were interviewed
      during 2012 using the Vederhus and Laudet questionnaire as a framework to explore
      the importance of the concepts of spirituality and religiosity and their possible
      roles in the treatment through patient's referral to mutual-help groups. The
      study's limitations are noted. 

PMID- 24041179
TI  - Spirituality and the health professional.
AB  - The inclusion of spirituality in addictions recovery began with the 12-steps
      program of Alcoholics Anonymous. Cofounded by Bill Wilson, the 12-steps'
      spiritual orientation is based on Wilson's own recovery from alcoholism that was
      associated with a spiritual experience. His correspondence with Carl Jung, who
      verified the importance of Wilson's experience, empowered Wilson to make
      spirituality central to the 12 steps. Spirituality remains a source of
      misunderstanding between the scientific, empirically informed mental health
      community, and the 12-step recovery movement. This article offers an outline of
      spiritual development, based on neuroscience, which the professional can utilize
      in the spiritual aspect of a patient's recovery. 

PMID- 24041180
TI  - Dharma, yoga, tantra.
AB  - In the mid-20th century, Selvararajan Yesudian (1916-1998), who was born in India
      to a Christian father, a physician, and spent most of his life in Switzerland,
      coauthored (with Elisabeth Haich) a book entitled Yoga and Health; since then,
      the coupling of these two words has largely defined the meaning of yoga in the
      West, especially in promotional literature for urban yoga schools and health-club
      programs. Authentic Indian traditions have indeed affirmed the therapeutic
      benefit of yoga, but they have consistently seen yoga as a "therapy of the soul,"
      a way of "quieting the agitations of the heart," to the end of perceiving the
      Ultimate within the soul and, in religious terms, of realizing union with God.
      This paper will examine some classical yoga texts in relation to spiritual
      remedies for substance misuse and other forms of addiction and chemical
      dependency. 

PMID- 24041178
TI  - Spirituality as a change mechanism in 12-step programs: a replication, extension,
      and refinement.
AB  - This National Institutes of Health funded study investigated spiritual growth as
      a change mechanism in 12-step programs. A total of 130 people, early 12-step
      affiliates with limited Alcoholics Anonymous (AA) histories, were recruited from
      2007 to 2008 from AA, treatment, and community centers in a Southwestern city in
      the United States. A majority of the sample was alcohol dependent. Participants
      were interviewed at baseline and at 3, 6, and 9 months. Lagged General Linear
      Modeling analyses indicated that spiritual change as measured by the Religious
      Background and Behavior (RBB) self-report questionnaire were predictive of
      increased abstinence and decreased drinking intensity, and that the magnitude of
      this effect varied across different RBB scoring algorithms. Future research
      should address study limitations by recruiting participants with more extensive
      AA histories and by including assessments of commitment to, and practice of, AA
      prescribed activities. The study's limitations are noted. 

PMID- 24041181
TI  - "What do you mean by spirituality? Please draw me a picture!" Complementary faith
      based addiction treatment in Switzerland from the client's perspective.
AB  - This article reviews: (1) the relative importance of spirituality and religion in
      Switzerland and the United States, (2) the rationale for faith-based addiction
      intervention programs and the drawbacks of measurement approaches, and (3)
      results from a pilot study exploring the meaning of spirituality and religiosity
      from the consumer's perspective. Twenty-three patients entering the Swiss Sudhang
      clinic in-patient alcohol user treatment program during the first five months in
      2012 participated upon their admission in a video-taped drawing task, designed to
      provide their personal visualized definitions of the terms "spirituality" and
      "religiosity." Nine dimensions emerged pointing to a high complexity of the
      concepts. 

PMID- 24041182
TI  - Spirituality in addictions treatment: wisdom to know...what it is.
AB  - Spirituality has long been integrated into treatments for addiction. However, how
      spirituality differs from other related constructs and implications for recovery
      among nonspiritual persons remains a source of discussion. This article examines
      ways in which spirituality is delineated, identifies variables that might mediate
      the relations between spirituality and recovery from substance abuse disorders,
      describes distinctions between spiritual and nonspiritual facets of addictions
      treatment, and suggests means to assist in further clarification of this
      construct. 

PMID- 24041184
TI  - The varieties of religious experience and the retention of clients in Taiwanese
      faith-based residential drug user treatment.
AB  - This study investigated whether subgroups of faith-based treatment clients
      displaying similar religious experiences and treatment performance can be
      theoretically specified and empirically identified. Highlighting the volitional
      dimension of the change process, four subgroups (i.e., non-Christians, baseline
      Christians, rededicated Christians, and newly converted Christians) were proposed
      according to the direction and magnitude of clients' change in religiosity during
      treatment. Data obtained for 707 subjects who entered a Christian residential
      therapeutic community program in Taiwan between 2000 and 2009 were analyzed.
      Results showed that the typology of religious experiences powerfully predicted
      treatment retention and completion. Issues of therapeutic specificity and relapse
      prevention are discussed and study's limitations are noted. 

PMID- 24041185
TI  - Spirituality, drugs, and alcohol: a philosophical analysis.
AB  - Spirituality has long been associated with recovery from the socially constructed
      "addictive disease." Alcoholics Anonymous (AA) and its analogs have enjoyed
      widespread acceptance as a spiritual approach for achieving recovery. AA or its
      derivatives are the predominant approaches in treatment programs even though a
      wide array of evidence-based approaches are now promoted by governmental sources
      in the United States. This philosophical analysis contrasts the state of science
      about addictive disorders with the reliance on a spiritual approach that is
      heavily grounded in Christian theology. We present four problems that need
      consideration before accepting the applicability of 12-step spiritual practices
      as the backbone of addiction treatment or recovery. 

PMID- 24041186
TI  - The roles of spirituality in the relationship between traumatic life events,
      mental health, and drug use among African American women from one southern state.
AB  - This study examines the role of spirituality as a moderator of the relationship
      between traumatic life experiences, mental health, and drug use in a sample of
      African American women. It was hypothesized that there would be an inverse
      relationship overall between spirituality and mental health and drug use among
      this sample of African American women. Secondly, was expected that spirituality
      would moderate the relationship between traumatic life events and mental health
      and drug use. African American women (n = 206) were recruited from the community
      and from probation officers in three urban areas of a southern state, and face-to
      face interviews were completed. Findings indicated that there was a main effect
      for spirituality (as measured by existential well-being on the Spiritual Well
      Being Scale) and traumatic life events, mental health, and alcohol use. In
      addition, spirituality was a significant moderator of the relationship between
      traumatic life events and cocaine use. Discussion and implications for African
      American women are included. 

PMID- 24041187
TI  - Addiction and spirituality.

PMID- 24041188
TI  - Paths through addiction and recovery: the impact of spirituality and religion.

PMID- 24041189
TI  - Spirituality, religion, and addiction: a possible epilogue.

PMID- 24041191
TI  - Nanopatterned smart polymer surfaces for controlled attachment, killing, and
      release of bacteria.
AB  - Model surfaces with switchable functionality based on nanopatterned,
      thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes were fabricated
      using interferometric lithography combined with surface-initiated polymerization.
      The temperature-triggered hydration and conformational changes of nanopatterned
      PNIPAAm brushes reversibly modulate the spatial concealment and exposure of
      molecules that are immobilized in the intervals between nanopatterned brushes. A
      biocidal quaternary ammonium salt (QAS) was used to demonstrate the utility of
      nanopatterned PNIPAAm brushes to control biointerfacial interactions with
      bacteria. QAS was integrated into polymer-free regions of the substrate between
      nanopatterned PNIPAAm brushes. The biocidal efficacy and release properties of
      these surfaces were tested against Escherichia coli K12. Above the lower critical
      solution temperature (LCST) of PNIPAAm, desolvated, collapsed polymer chains
      facilitate the attachment of bacteria and expose QAS moieties that kill attached
      bacteria. Upon a reduction of the temperature below the LCST, swollen PNIPAAm
      chains promote the release of dead bacteria. These results demonstrate that
      nanopatterned PNIPAAm/QAS hybrid surfaces are model systems that exhibit an
      ability to undergo noncovalent, dynamic, and reversible changes in structure that
      can be used to control the attachment, killing, and release of bacteria in
      response to changes in temperature. 

PMID- 24041192
TI  - IDSR as a platform for implementing IHR in African countries.
AB  - Of the 46 countries in the World Health Organization (WHO) African region (AFRO),
      43 are implementing Integrated Disease Surveillance and Response (IDSR)
      guidelines to improve their abilities to detect, confirm, and respond to high
      priority communicable and noncommunicable diseases. IDSR provides a framework for
      strengthening the surveillance, response, and laboratory core capacities required
      by the revised International Health Regulations [IHR (2005)]. In turn, IHR
      obligations can serve as a driving force to sustain national commitments to IDSR
      strategies. The ability to report potential public health events of international
      concern according to IHR (2005) relies on early warning systems founded in
      national surveillance capacities. Public health events reported through IDSR to
      the WHO Emergency Management System in Africa illustrate the growing capacities
      in African countries to detect, assess, and report infectious and noninfectious
      threats to public health. The IHR (2005) provide an opportunity to continue
      strengthening national IDSR systems so they can characterize outbreaks and
      respond to public health events in the region. 

PMID- 24041193
TI  - Communications in public health emergency preparedness: a systematic review of
      the literature.
AB  - During a public health crisis, public health agencies engage in a variety of
      public communication efforts to inform the population, encourage the adoption of
      preventive behaviors, and limit the impact of adverse events. Given the
      importance of communication to the public in public health emergency
      preparedness, it is critical to examine the extent to which this field of study
      has received attention from the scientific community. We conducted a systematic
      literature review to describe current research in the area of communication to
      the public in public health emergency preparedness, focusing on the association
      between sociodemographic and behavioral factors and communication as well as
      preparedness outcomes. Articles were searched in PubMed and Embase and reviewed
      by 2 independent reviewers. A total of 131 articles were included for final
      review. Fifty-three percent of the articles were empirical, of which 74% were
      population-based studies, and 26% used information environment analysis
      techniques. None had an experimental study design. Population-based studies were
      rarely supported by theoretical models and mostly relied on a cross-sectional
      study design. Consistent results were reported on the association between
      population socioeconomic factors and public health emergency preparedness
      communication and preparedness outcomes. Our findings show the need for empirical
      research to determine what type of communication messages can be effective in
      achieving preparedness outcomes across various population groups. They suggest
      that a real-time analysis of the information environment is valuable in knowing
      what is being communicated to the public and could be used for course correction
      of public health messages during a crisis. 

PMID- 24041194
TI  - The human-animal interface and zoonotic threats: the Russian Federation approach.
AB  - Zoonotic pathogens have caused the majority of emerging infectious disease events
      in the past 6 decades. With most emerging infectious diseases arising from animal
      origins, including many of the select agents identified as most likely candidates
      for bioterrorism, linking human and animal surveillance systems will be critical
      to effective disease identification and control in the future. Lack of this
      linkage has been the focus of a number of important policy papers in recent
      years. These have expressed concern over the continued lack of preparedness for
      addressing zoonotic threats and have called for a new approach to integrating
      biosurveillance. However, these studies have been mainly Western-centric in
      viewpoint and have overlooked the example of the Russian Federation (RF) Anti
      Plague System (AP system). In this article we submit that the RF AP system has
      select components that effectively address recent concerns and inform the US and
      UK intersectoral efforts on human-animal health surveillance, forming a basis for
      US, UK, and RF collaboration. 

PMID- 24041195
TI  - EMAC volunteers: liability and workers' compensation.
AB  - The Emergency Management Assistance Compact (EMAC) provides a mechanism for
      states to assist each other during natural disasters and other emergencies.
      Congress ratified EMAC in 1996, and all 50 states and 3 territories have adopted
      it. EMAC allows a state affected by a disaster to request personnel and materiel
      from another state. For personnel requests, EMAC provides that the requesting
      state cover the tort liability and the responding state cover the workers'
      compensation liability. This article discusses the limitations of EMAC in
      deploying volunteers and how the Uniform Emergency Volunteer Health Practitioners
      Act and other provisions address those limitations.

PMID- 24041196
TI  - The plague of Athens: an ancient act of bioterrorism?
AB  - Recent data implicate Salmonella enterica serovar Typhi as a causative pathogen
      of the Plague of Athens during the Peloponnesian War (430-426 bc). According to
      Thucydides, the sudden outbreak of the disease may link to poisoning of the water
      reservoirs by the Spartans. The siege of a city was aimed at exhausting the
      supplies of a population, which often led to the outbreak and spread of
      epidemics. Poisoning of the water reservoirs of a besieged city as an act of
      bioterrorism would probably shorten the necessary time for such conditions to
      appear. 

PMID- 24041198
TI  - First self-adjuvant multicomponent potential vaccine candidates by tethering of
      four or eight MUC1 antigenic immunodominant PDTRP units on a calixarene platform:
      synthesis and biological evaluation.
AB  - MUC1 protein overexpressed in human epithelial carcinoma is a target in
      development of novel anticancer vaccines. Multiple units of immunodominant B-cell
      epitope PDTRP MUC1 core sequence were conjugated to calix[4,8]arene platforms
      containing TLR2 ligand, to produce two novel anticancer self-adjuvant vaccine
      candidates. The immunogenicity of the synthetic constructs was investigated by
      immunization of mice in vivo. ELISA assay evidenced that the vaccine candidates
      stimulate anti MUC1 IgG antibody production (major for the octavalent construct)
      and no additive effect but a multivalency effect was observed when compared to an
      analogous monovalent. Octa- and tetravalent constructs lacking in PDTRP peptide
      moieties did not show anti MUC1 IgG antibody production in mice. The antibodies
      induced by the synthesized constructs are able to recognize the MUC1 structures
      present on MCF7 tumor cells. The results display that calixarenes are convenient
      platforms for building multicomponent self-adjuvant vaccine constructs promising
      as immunotherapeutic anticancer agents. 

PMID- 24041199
TI  - Internet-based guided self-help for several anxiety disorders: a randomized
      controlled trial comparing a tailored with a standardized disorder-specific
      approach.
AB  - Internet-delivered self-help with minimal therapist guidance has shown promising
      results for a number of diagnoses. Most of the evidence comes from studies
      evaluating standardized disorder-specific treatments. A recent development in the
      field includes transdiagnostic and tailored Internet-based treatments that
      address comorbid symptoms and a broader range of patients. This study evaluated
      an Internet-based tailored guided self-help treatment, which targeted symptoms of
      social anxiety disorder, panic disorder with or without agoraphobia, and
      generalized anxiety disorder. The tailored treatment was compared both with
      standardized disorder-specific Internet-based treatment and with a wait-list
      control group. Both active treatment conditions were based on cognitive
      behavioral therapy and lasted for 8 weeks. A total of 132 individuals meeting
      diagnostic criteria for at least one of the anxiety disorders were randomly
      assigned to 1 of the 3 conditions. Both treatment groups showed significant
      symptom reductions as compared with the wait-list control group on primary
      disorder-unspecific measures of anxiety, depression, and general symptomatology
      and on secondary anxiety disorder-specific measures. Based on the intention-to
      treat sample, mean between-group effect sizes were d = 0.80 for the tailored
      treatment and d = 0.82 for the standardized treatment, versus wait-list controls.
      Treatment gains were maintained at 6-month follow-up. No differences were found
      between the 2 active treatment conditions on any of the measures, including a
      telephone-administered diagnostic interview conducted at posttreatment. The
      findings suggest that both Internet-based tailored guided self-help treatments
      and Internet-based standardized treatments are promising treatment options for
      several anxiety disorders.

PMID- 24041201
TI  - Vacuum ultraviolet photodissociation dynamics of isocyanic acid: the hydrogen
      elimination channel.
AB  - Photodissociation dynamics of the H-atom channel from HNCO photolysis between 124
      and 137 nm have been studied using the H-atom Rydberg tagging time-of-flight
      technique. Product translational energy distributions and angular distributions
      have been determined. Two dissociation channels, H + NCO (X(2)Pi) and H +
      NCO(A(2)Sigma(+)), have been observed. The former channel involves two different
      dissociation pathways; one is a slow predissociation pathway through internal
      conversion from the excited state to the S0 state, and the other is a fast
      predissociation pathway through internal conversion from the excited state to the
      S1 state. The latter channel dominates by a prompt dissociation via coupling to
      the S2 state. As the photon energy increases, dissociation on the ground state S0
      becomes dominant. Vibrational structures are observed in both the NCO(X) and
      NCO(A) channels, which can be assigned to the bending mode excitation with some
      stretching vibrational excitation. 

PMID- 24041200
TI  - Association of thiazolidinediones with gastric cancer in type 2 diabetes
      mellitus: a population-based case-control study.
AB  - BACKGROUND: It has been shown that peroxisome proliferator-activated receptors
      (PPAR) have physiological and pharmacological ligands. The objective is to assess
      the association between thiazolidinediones (TZDs) and the occurrence of gastric
      cancer. METHODS: We conducted a population-based nested case-control study. Data
      were retrospectively collected from the National Health Insurance Research
      Database (NHIRD). The cases consisted of all diabetes mellitus (DM) patients aged
      30 to 99 years, and who had a first time diagnosis of gastric cancer in the study
      cohort. The controls were matched to cases by age, sex, and index date. The
      adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by using
      multiple logistic regression. RESULTS: Records from 357 gastric cancer and 1,428
      selected matched controls were included in the analyses of gastric cancer risk. A
      total of 7% or 9.5% of the cases and 10.8% or 14.8% of the controls had used any
      quantity of at least 2 prescriptions for pioglitazone or rosiglitazone,
      respectively. After adjusting for possible confounders, pioglitazone (OR = 0.93,
      P > 0.05) and rosiglitazone (OR = 1.21, P > 0.05), had no significant association
      of decreasing gastric cancer. After adjusting for possible confounders,
      pioglitazone (OR = 0.70, P > 0.05) or rosiglitazone (OR = 0.79, P > 0.05), had no
      significant trend toward decreasing gastric cancer risk with increasing
      cumulative doses >= 260 defined daily doses (DDDs), respectively. Moreover,
      adjusting for possible confounders pioglitazone (OR = 0.68, P > 0.05) or
      rosiglitazone (OR = 0.74, P > 0.05) had no significant trend toward decreasing
      gastric cancer risk with increasing cumulative doses >= 1 year, respectively.
      CONCLUSIONS: Our results did not show evidence to support that TZD derivatives in
      DM patients reduces gastric cancer occurrence.

PMID- 24041202
TI  - Angiogenic growth factors in maternal and fetal serum in concordant and
      discordant twin pregnancies.
AB  - OBJECTIVE: To assess soluble fms-like tyrosin kinase 1 (sFlt-1), free vascular
      endothelial growth factor (f-VEGF) and the f-VEGF/sFlt-1 quotient in twin
      pregnancies, and to determine if they are impaired in discordant twins. METHODS:
      Case-control study between 18 discordant and 46 concordant twin pregnancies.
      Angiogenic growth factors were measured in maternal serum during pregnancy and in
      umbilical artery and vein at birth. RESULTS: Discordant twins were more often
      conceived by assisted reproductive techniques than concordant twins. Maternal
      plasma f-VEGF was significantly lower in discordant twins (p = 0.04). F-VEGF and
      f-VEGF/sFlt-1 in the whole sample show a significant higher level in concordant
      twins. When we analyzed umbilical cord angiogenic factors, the smaller twin had a
      lower f-VEGF/sFlt-1 quotient (p = 0.01). We found no correlations between
      maternal or umbilical growth factors and placental or fetal weight. No difference
      was found in veno-arterial levels of angiogenic factors in each twin; however,
      there was a significant rise in arterial f-VEGF (p = 0.06) in discordant twins.
      CONCLUSION: Mothers of discordant twins have a more anti-angiogenic environment
      compared to those of concordant twins. We also found an anti-angiogenic
      environment in the small twin when we compared umbilical vein angiogenic factors
      against its big co-twin.

PMID- 24041203
TI  - Engineering V-type nerve agents detoxifying enzymes using computationally focused
      libraries.
AB  - VX and its Russian (RVX) and Chinese (CVX) analogues rapidly inactivate
      acetylcholinesterase and are the most toxic stockpile nerve agents. These
      organophosphates have a thiol leaving group with a choline-like moiety and are
      hydrolyzed very slowly by natural enzymes. We used an integrated computational
      and experimental approach to increase Brevundimonas diminuta phosphotriesterase's
      (PTE) detoxification rate of V-agents by 5000-fold. Computational models were
      built of the complex between PTE and V-agents. On the basis of these models, the
      active site was redesigned to be complementary in shape to VX and RVX and to
      include favorable electrostatic interactions with their choline-like leaving
      group. Small libraries based on designed sequences were constructed. The
      libraries were screened by a direct assay for V-agent detoxification, as our
      initial studies showed that colorimetric surrogates fail to report the
      detoxification rates of the actual agents. The experimental results were fed back
      to improve the computational models. Overall, five rounds of iterating between
      experiment and model refinement led to variants that hydrolyze the toxic SP
      isomers of all three V-agents with kcat/KM values of up to 5 * 10(6) M(-1) min(
      1) and also efficiently detoxify G-agents. These new catalysts provide the basis
      for broad spectrum nerve agent detoxification. 

PMID- 24041204
TI  - Effects of vaginal septa on the reproductive performance of BALB/cByJNarl mice.
AB  - From March through December 2010, the incidence of vaginal septa in our SPF
      breeding colony of BALB/cByJNarl mice was 14.2%. In general, septa obstructed
      half of the vaginal orifice. Here we sought to determine the effect of this
      defect by comparing the reproductive performance of affected (septate) mice with
      that of unaffected (nonseptate) mice. Our results showed that the rates of both
      copulatory plugs and pregnancy were significantly lower in septate mice than in
      nonseptate mice. Specifically, 23 of 45 bred septate female mice (51%) had
      vaginal plugs compared with 49 of 68 bred nonseptate females (72%). Only 12
      septate female mice (27%) had successful pregnancies, compared with 37 nonseptate
      females (54%). Septate mice had a 1-logfold fewer intrauterine sperm after mating
      than did nonseptate mice. Three cases of dystocia were noted among septate mice
      whereas none occurred in nonseptate mice. Septate dams had a higher percentage of
      septate pups (15.5%) than did nonseptate dams (6.1%). Our findings indicate that
      vaginal septa affect the reproductive performance of laboratory mice and that
      such a defect should be considered as an exclusion criterion for the selection of
      future breeders in a mouse colony. 

PMID- 24041205
TI  - Controlled exercise is a safe pregnancy intervention in mice.
AB  - During pregnancy, women often show a willingness to make positive lifestyle
      changes, such as smoking cessation, initiation of a vitamin regimen, improvement
      of their diet, and increases in their levels of exercise or physical activity. To
      study health outcomes in both pregnant mice and their offspring, we developed a
      model of controlled maternal exercise during mouse pregnancy. Female ICR and
      C57BL/6 mice underwent controlled wheel walking for 1 h daily, 5 d each week, at
      a speed of 6 m/min prior to and during pregnancy and nursing. Dam body weight,
      food consumption, pregnancy rates, litter size, pup weights and litter survival
      were used as markers of pregnancy success and were not significantly affected by
      controlled maternal exercise. The proposed exercise paradigm is a safe pregnancy
      intervention and can be explored further. 

PMID- 24041206
TI  - Effect of nesting material on body weights of mice infected with Toxoplasma
      gondii.
AB  - Toxoplasmosis, a disease caused by the parasitic protozoan Toxoplasma gondii, can
      cause a number of clinical signs in mice, including weight loss. This weight loss
      likely is related to the host immune response and is important to monitor in
      Toxoplasma studies. Several studies have demonstrated that nesting material can
      affect body weights of mice. We therefore sought to assess the effects of nesting
      material on body weights of mice infected with Toxoplasma. We housed mice with or
      without nesting material and weighed and clinically assessed them twice weekly
      for 30 days prior to and 5 wk after Toxoplasma inoculation. Nesting material did
      not significantly alter the weights of mice after Toxoplasma inoculation but did
      decrease rates of growth prior to inoculation. Nesting material did not affect
      the clinical outcome of Toxoplasma infections, supporting the provision of
      nesting material in mouse Toxoplasma experiments. 

PMID- 24041207
TI  - Play caging benefits the behavior of singly housed laboratory rhesus macaques
      (Macaca mulatta).
AB  - This study addresses a recommendation in The Guide for the Care and Use of
      Laboratory Animals to provide singly housed nonhuman primates with intermittent
      access to large, enriched (play) caging. Research on the potential benefits of
      this type of caging is limited. The present study examines the effects of play
      caging on behavior, activity, and enrichment use. Singly housed, adult male,
      rhesus macaques (n = 10) underwent a baseline phase in their home cages, a 2-wk
      treatment phase with housing in play cages, and a posttreatment phase after
      returning to their home cages. Each subject underwent focal behavioral
      observations (n = 10; duration 30 min each) during each study phase, for a total
      of 150 h of data collection. Results showed increases in locomotion and
      enrichment use and a trend toward decreased abnormal behavior while subjects were
      in the play cage, with the durations of these behaviors returning to baseline
      levels after treatment. Anxiety-related behaviors decreased between the treatment
      and posttreatment phases but not between baseline and treatment, suggesting that
      outside factors may have influenced the decline. During the treatment phase,
      subjects spent more time in the upper quadrants of the play caging and preferred
      a mirror and forage boards as forms of enrichment. The greatest behavioral
      improvement occurred during the first week in the play cage. This study provides
      evidence to support the benefits of play caging for singly housed rhesus
      macaques. 

PMID- 24041208
TI  - Environmental monitoring for Aspergillus fumigatus in association with an
      immunosuppressed rabbit model of pulmonary aspergillosis.
AB  - Aspergillus fumigatus causes life-threatening pneumonia in immunocompromised
      patients. Conidia, the infectious form of the organism, are handled in a biologic
      safety cabinet under BSL2 conditions. However because germinated conidia form
      noninfectious hyphae in tissue, we hypothesized that rabbits inoculated
      intratracheally would grow A. fumigatus in their lungs but that the environment
      would remain free of this fungus, potentially permitting maintenance of infected
      animals under ABSL1 conditions. We performed a surveillance study for the
      presence of A. fumigatus in the environment before proceeding with antifungal
      therapy studies of experimental pulmonary aspergillosis. The expected outcome
      included absence of A. fumigatus in the environment, stool, and blood and
      presence in rabbit lungs. Female SPF New Zealand white rabbits were
      immunosuppressed and inoculated intratracheally (n = 4) or intraesophageally (n =
      2) with 1.25 * 10(8) conidia of A. fumigatus. Feces, pan liners, and walls were
      sampled daily during the 11-d experiment, and blood was sampled on days 2, 6, and
      8 after inoculation. Samples were cultured on 5% Sabouraud glucose agar plates.
      Lungs were weighed and scored for hemorrhagic infarcts and homogenized for
      culture on 5% Sabouraud glucose agar and trypticase soy agar plates. Blood
      cultures, rabbit stool, and environmental swabs were all negative for A.
      fumigatus whereas the lungs inoculated intratracheally demonstrated 4.5 * 10(2)
      +/- 0.8 * 10(2) CFU/g of A. fumigatus. Therefore, neutropenic rabbits with
      experimental invasive pulmonary aspergillosis do not shed conidia of A. fumigatus
      and can be safely housed under ABSL1 conditions after inoculation. 

PMID- 24041209
TI  - Immunopathologic characterization of naturally acquired Trypanosoma cruzi
      infection and cardiac sequalae in cynomolgus macaques (Macaca fascicularis).
AB  - Trypanosoma cruzi, the causative agent of Chagas disease, is endemic in south
      Texas due to the abundant vector and wild small mammalian reservoir populations.
      This situation predisposes nonhuman primate colonies exposed to outdoor housing
      to infection from ingestion or bite of triatomid insects. Using a T. cruzi
      specific real-time PCR and Trypanosome spp.-specific ELISA, we revealed a
      prevalence rate of 8.5% in a colony of outdoor-housed cynomolgus macaques. By
      using a discriminating kinetoplastid minicircle PCR, we eliminated the
      possibility of mixed prevalence with nonpathogenic trypanosomes and showed the
      ELISA results were specific for T. cruzi. In this study, we found an inverse
      relationship between antibody titers and circulating parasite load. Also, 23% of
      T. cruzi IgG ELISA-positive macaques were negative by real-time PCR. Furthermore,
      in a subset of infected macaques, cardiac tissue was infiltrated by inflammatory
      mononuclear cells and contained T. cruzi genomic and kinetoplast DNA despite
      lacking microscopic evidence of discrete parasite stages. In addition, 19% of the
      infected macaques had titers for cardiac troponin I autoantibody, which could
      contribute to autoimmune myocarditis or interfere with circulating troponin I
      measurements. These findings indicate the possibility of T. cruzi to interfere
      with the assessment of cardiac safety signals in preclinical toxicology and
      safety pharmacology studies and the necessity for prestudy screening for T. cruzi
      in outdoor-housed nonhuman primates from endemic areas. 

PMID- 24041210
TI  - Aqueous stability and oral pharmacokinetics of meloxicam and carprofen in male
      C57BL/6 mice.
AB  - We found that carprofen and meloxicam under 3 environmental conditions (ambient
      dark, ambient light, and 4  degrees C) remained stable for at least 7 d. We then
      evaluated the oral pharmacokinetics of meloxicam (20 mg/kg) and carprofen (10
      mg/kg) in male C57BL/6 mice after oral gavage or administration in the drinking
      water. Mice did not drink meloxicam-medicated water but readily consumed
      carprofen-medicated water, consuming an average of 14.19 mL carprofen-medicated
      water per 100 g body weight daily; mice drank more during the dark phase than
      during the light phase. Plasma analyzed by HPLC (meloxicam) and tandem mass
      spectrometry (carprofen) revealed that the peak meloxicam and carprofen
      concentrations were 16.7 and 20.3 MUg/mL and occurred at 4 and 2 h after oral
      gavage, respectively. Similar blood levels were achieved after 12 h access to the
      carprofen-medicated water bottle. At 24 h after oral gavage, the drugs were not
      detectable in plasma. Meloxicam plasma AUC, elimination half-life, apparent
      volume of distribution, and apparent oral clearance were 160.4 mg/L * h, 7.4 h,
      0.36 L/kg, and 0.125 mL/h * kg, respectively. Carprofen plasma AUC, elimination
      half-life, apparent volume of distribution, and apparent oral clearance were
      160.8 mg/L * h, 7.4 h, 0.42 L/kg, and 0.062 mL/h * kg, respectively. No gross or
      microscopic evidence of toxicity was seen in any mouse. Our findings indicate
      that carprofen can be administered in drinking water to mice and that medicated
      water bottles should be placed 12 to 24 h prior to painful procedures. 

PMID- 24041211
TI  - Hemodynamic and behavioral differences after administration of meloxicam,
      buprenorphine, or tramadol as analgesics for telemeter implantation in mice.
AB  - Cannulation of the common carotid artery for chronic, continuous radiotelemetric
      recording of aortic hemodynamic properties in mice is a highly invasive recovery
      surgery. Radiotelemetric recording, by its continuous nature, gives the most
      accurate measurements of hemodynamic variables in experimental animals, and is
      widely used in the study of cardiovascular diseases including hypertension. The
      American Heart Association has recommended data acquisition by radiotelemetric
      recording but did not provide guidelines regarding postoperative analgesic
      support. We assessed hemodynamic parameters, locomotor activity, food intake, and
      weight loss in radiotransmitter-implanted CD1 female mice receiving analgesic
      support during the first 48 h after surgery. The efficacy of analgesic support
      from the NSAID meloxicam was compared with that of the widely used opioid agonist
      buprenorphine and the related compound, tramadol. Meloxicam-treated mice
      recovered lost body weight more rapidly than did tramadol-or buprenorphine
      treated mice. Furthermore, meloxicam-treated mice maintained circadian rhythm
      after surgery and had tighter regulation of mean arterial pressure than did
      tramadol- or buprenorphine-treated mice. Meloxicam was also superior with regard
      to food intake, locomotor activity, and limiting variance in hemodynamic
      parameters. This study indicates that when compared with buprenorphine and
      tramadol, meloxicam should be the postoperative analgesic of choice for
      radiotelemeter implantation in mice. 

PMID- 24041212
TI  - Pharmacokinetics of ketamine and xylazine in young and old Sprague-Dawley rats.
AB  - To compare the pharmacokinetics of coadministered intraperitoneal ketamine and
      xylazine in young (8 to 10 wk; n = 6) and old rats (2 to 2.4 y; n = 6), blood
      samples obtained at 15 and 30 min and 1, 2, and 4 h after drug administration
      were analyzed by HPLC-tandem mass spectrometry. In both groups, the withdrawal
      reflex was absent during anesthesia and was present at 1.1 (+/- 0.2) and 2.6 (+/-
      0.7) h after drug administration in young and old rats, respectively, with the
      first voluntary movement at 1.5 +/- 0.2 and 4.9 +/- 1.0 h. Drug availability of
      ketamine and xylazine was 6.0 and 6.7 times greater, respectively, in old than
      young rats. The rate constant of elimination of both drugs was greatly decreased
      and the elimination half-life was significantly greater in old compared with
      young rats. In conclusion, age and associated factors affect the availability of
      ketamine and xylazine when coadministered to attain clinical anesthesia, changing
      the pharmacokinetics of these drugs and prolonging anesthesia duration and
      recovery times with aging. Compared with their young counterparts, aged rats
      required much higher doses to attain a similar level of anesthesia. Finally, the
      long half-life of both ketamine and xylazine, when coadministered to old rats,
      may be a factor in research protocols because residual plasma concentrations
      could still be present for as long as 3 and 5 d, respectively, after
      administration. 

PMID- 24041213
TI  - Effects of multimodal analgesia with LowDose buprenorphine and meloxicam on fecal
      glucocorticoid metabolites after surgery in New Zealand white rabbits
      (Oryctolagus cuniculus).
AB  - Despite the increasing use of rabbits as companion animals and models for
      biomedical research, rabbits have not been extensively studied to identify an
      efficacious postsurgical analgesic that does not cause systemic complications.
      The synergy of NSAID and systemic opioids is well-documented, and their combined
      use reduces the amount of either drug required for adequate analgesia. We
      measured fecal corticosterone metabolites (FCM) in rabbits after a minimally
      invasive vascular cut-down procedure. Rabbits received buprenorphine (0.03 mg/kg
      SC every 12 h for 3 d), meloxicam (0.2 mg/kg SC every 24 h for 3 d),
      buprenorphine-meloxicam (0.01 mg/kg-0.1 mg/kg SC every 24 h for 3 d), or a single
      dose of 0.5% bupivacaine (0.5 mL) infused locally at the incision site. By day 3
      after surgery, buprenorphine, meloxicam, and bupivacaine groups showed elevated
      FCM levels, which continued to rise until day 7 and then gradually returned to
      baseline by day 28. In the buprenorphine-meloxicam group, FCM was relatively
      unchanged until day 3, when treatment was discontinued, and then began to rise.
      Rabbits in the buprenorphine-meloxicam group gained more weight over the 28-d
      study than did those in the other 3 treatment groups. This study shows that in
      rabbits low-dose buprenorphine administered with meloxicam effectively mitigates
      the FCM response that develops after surgery without the adverse effects
      associated with higher doses. 

PMID- 24041214
TI  - Comparison of thermoregulatory devices used during anesthesia of C57BL/6 mice and
      correlations between body temperature and physiologic parameters.
AB  - General anesthesia affects several body systems, including thermoregulation.
      Decreased body temperature during anesthesia has potential negative effects,
      including delayed recovery to consciousness. Thermoregulatory support devices are
      used to maintain temperature in anesthetized rodents. We analyzed 2 novel
      thermoregulatory devices, thermogenic gel packs and reflective foils, to compare
      their effectiveness in maintaining temperatures with that of a standard
      circulating-warm-water blanket (CWWB) in C57BL/6 mice. Mice were grouped
      randomly: control (no thermal support), reflective foil, gel pack, gel pack plus
      reflective foil, CWWB on medium setting, CWWB on high setting, and CWWB on high
      setting plus reflective foil. Mice were anesthetized with isoflurane for 30 min,
      and temperature and heart and respiratory rates were monitored. Results indicated
      that the temperatures of mice with reflective foil only (start temperature, 36.2
      +/- 0.38  degrees C; end temperature, 28.8 +/- 0.78  degrees C) did not differ
      significantly from those of control mice; however, the inclusion of foil
      heightened thermogenic properties when combined with other devices. Thermogenic
      gel packs and CWWB on high setting, both with and without reflective foil, caused
      significant temperature increases (that is, 1.6  degrees C to 4.4  degrees C) in
      mice. CWWB on medium setting (blanket temperature, 37.5  degrees C) maintained
      mice at temperatures within 1  degrees C of the 36.1  degrees C baseline. Strong
      correlations existed between temperature, heart and respiratory rates, and
      recovery time to consciousness. This information provides guidance regarding the
      use of thermoregulatory devices in anesthetized rodents and demonstrates the
      effect of maintaining a consistent core temperature on physiologic parameters. 

PMID- 24041215
TI  - A novel noninvasive method for evaluating experimental lung metastasis in mice.
AB  - Metastasis remains the most significant problem in the field of cancer. The
      biologic complexity that characterizes metastasis requires relevant in vivo
      models. When using murine models for pulmonary metastasis, longitudinal studies
      are valuable for following the progression of metastatic burden. Currently, the
      progression of pulmonary metastatic burden in experimental mice over time is
      monitored through advanced imaging approaches or the clinical assessment of
      morbidity. Because clinical signs of morbidity are often vague and unpredictable,
      an inexpensive and reproducible method to detect advanced metastatic burden
      before the development of mortality-is needed. We have developed a noninvasive
      technique for assessing pulmonary metastatic burden in laboratory mice. The
      pulmonary assessment of advanced metastasis (PAAM) test is performed by
      restraining an awake mouse and gently applying pressure with the index finger
      under the xiphoid process. This pressure reduces the diaphragmatic component to
      respiration. Mice with advanced lung metastases show transient signs of
      respiratory distress within 3 s of the application of this pressure. Using PAAM
      in 4 distinct models (including sarcoma and mammary carcinoma histologies) of
      experimental (tail vein) pulmonary metastasis (n = 114 mice), among 3 independent
      evaluators yielded 94% positive and negative predictive values, which were
      validated by histologic assessment of postmortem lung tissue. PAAM is a simple,
      reproducible, and efficient method to assist in the detection of advanced
      pulmonary metastasis in mice and contributes to their humane care during
      longitudinal studies. 

PMID- 24041216
TI  - Platelet aggregation in rhesus macaques (Macaca mulatta) in response to short
      term meloxicam administration.
AB  - NSAID administration is often chosen as a method of minimizing pain and
      discomfort for nonhuman primates. Of concern when using NSAID is the potential
      for decreased platelet aggregation due to the inhibition of cyclooxygenases 1 and
      2. In both dogs and humans, the use of NSAID that are selective for
      cyclooxygenase 2, like meloxicam, minimizes the inhibition of platelet
      aggregation in comparison to nonselective NSAID, like aspirin, that inhibit both
      isoforms of cyclooxygenase. In this study, we measured platelet aggregation in
      rhesus macaques (n = 6) by using the impedance method on a multiple-electrode
      aggregometer at baseline, at 1 and 4 d after initiating treatment with aspirin or
      meloxicam, and after a washout period. There was no statistical difference
      between aggregation at baseline and after 1 or 4 d of meloxicam treatment, but
      platelet aggregation decreased after both 1 and 4 d of aspirin therapy. Our data
      suggest that clinically significant postoperative hemorrhage is unlikely in
      rhesus macaques briefly treated with meloxicam. 

PMID- 24041218
TI  - From antiferromagnetic to ferromagnetic interaction in cyanido-bridged Fe(III)
      Ru(II)-Fe(III) complexes by change of the central diamagnetic cyanido-metal
      geometry.
AB  - Cis- and trans-isomeric heterotrinuclear-metallic complexes and their two
      electron-oxidation products, cis-/trans-[Cp(dppe)Fe(MU-CN)Ru(bpy)2(MU
      CN)Fe(dppe)Cp][PF6]2 (cis-/trans-1[PF6]2) and cis-/trans-[Cp(dppe)Fe(MU
      CN)Ru(bpy)2(MU-CN)Fe(dppe)Cp][PF6]4 (cis-/trans-1[PF6]4), have been synthesized
      and structurally characterized. To the best of our knowledge, the complexes are
      the first example of a cis-/trans-isomer with multistates. Although separated by
      the diamagnetic cyanido-metal bridge, the two distant paramagnetic metal centers
      in both the oxidized complexes exhibit quite strong magnetic couplings. As a
      unique example, cis-1[PF6]4 is antiferromagnetic, and trans-1[PF6]4 is
      ferromagnetic. Density functional theory (DFT) calculations suggest that the spin
      delocalization mechanism should be responsible for the magnetic interactions
      between the two distant paramagnetic Fe(III) centers across the diamagnetic
      cyanido-metal in both cis- and trans-1(4+). Most importantly, the DFT
      calculations revealed that the type (antiferromagnetic or ferromagnetic) and
      strength (J) of the magnetic interactions in such compounds can be controlled by
      the variation (cis or trans) of the diamagnetic central metal configurations. 

PMID- 24041220
TI  - Hexane soluble extract of Mallotus philippensis (Lam.) Muell. Arg. root possesses
      anti-leukaemic activity.
AB  - BACKGROUND: Mallotus philippensis (Lam.) Muell. Arg. is a well known medicinal
      plant of Asia and Australia. Various compounds from different aerial parts of the
      plant have been reported possessing potent pharmacological, antiviral,
      antibacterial and cytotoxic activities. We were interested to determine the
      effects of some root extracts from M. philippensis on human promyelocytic
      leukemia HL-60 cell proliferation, cell cycle regulators and apoptosis in order
      to investigate its anti-leukemic potential. RESULTS: Root extract of M.
      philippensis was initially extracted in organic solvents, hexane, ethyl acetate,
      and n-butanol. The hexane extract showed highest toxicity against p53-deficient
      HL-60 cells (IC50 1.5 mg dry roots equivalent/ml medium) after 72 h and
      interestingly, inhibition of cell proliferation was preceded by the upregulation
      of the proto-oncogenes Cdc25A and cyclin D1 within 24 h. The hexane extract
      induced 18% apoptosis after 48 h of treatment. Chemical composition of the hexane
      extract was analyzed by GC-MS and the 90% fragments were matched with
      polyphenolic compounds. CONCLUSIONS: The present study confirms that the hexane
      fraction of M. philippensis root extract possesses anti-leukemic activity in HL
      60 cells. The polyphenols were the main compounds of the hexane extract that
      inhibited proliferation and induced apoptosis.

PMID- 24041219
TI  - Land-based versus aquatic resistance therapeutic exercises for older women with
      sarcopenic obesity: study protocol for a randomised controlled trial.
AB  - BACKGROUND: Sarcopenic obesity is a health condition that combines excess adipose
      tissue and loss of muscle mass and strength. Sarcopenic obesity predisposes to
      more functional disabilities than obesity or sarcopenia alone. Progressive
      resistance exercises are recommended for older people as a potential treatment
      for sarcopenia and also for obesity. However, there is a lack of evidence
      indicating which programmes are best applied to older people, and no studies have
      investigated their effects on sarcopenic obese people. The aims of this protocol
      study are to investigate and compare the efficacy of land-based and aquatic
      resistance exercise programmes on improving muscle performance, functional
      capacity and quality of life of older women with sarcopenic obesity.
      METHODS/DESIGN: This is a protocol study for a parallel randomised controlled
      clinical trial. Eligible participants are older women (>=65 years) with a body
      mass index >=30 kg/m 2 and hand grip strength <=21 kg force. A total sample of 36
      participants will be randomly allocated to one of the intervention groups in
      blocks of three: land-based, aquatic or control. Each intervention group will
      undergo 2-week sessions of a 10-week therapeutic exercise programme for strength,
      power and endurance training of the lower-limb muscles. Participants in the
      control group will not participate in any strengthening activity for lower limbs
      and will receive telephone calls once a week. Baseline and final evaluation of
      outcomes will encompass muscle performance of the lower limbs assessed by an
      isokinetic dynamometer; functional tests of usual walking speed, maximal walking
      speed (shuttle walking test), stair speed and the Short Physical Performance
      Battery; and health-related quality of life (Medical Outcomes Study Short Form
      Questionnaire - SF-36). Data collectors will be blinded to randomisation and will
      not be in touch with participants during the interventions. DISCUSSION: This
      study is the first randomised controlled trial designed to evaluate resistance
      exercises in older patients with sarcopenic obesity. If our hypothesis proves
      correct, both intervention programmes will be effective, with the land-based
      exercises conferring better results in muscle performance. TRIAL REGISTRATION:
      Registro Brasileiro de Ensaios Clinicos: RBR-9p5q67.

PMID- 24041221
TI  - Runaway electrification of friable self-replicating granular matter.
AB  - We establish that the nonlinear dynamics of collisions between particles favors
      the charging of an insulating, friable, self-replicating granular material that
      undergoes nucleation, growth, and fission processes; we demonstrate with a
      minimal dynamical model that secondary nucleation produces a positive feedback in
      an electrification mechanism that leads to runaway charging. We discuss ice as an
      example of such a self-replicating granular material: We confirm with laboratory
      experiments in which we grow ice from the vapor phase in situ within an
      environmental scanning electron microscope that charging causes fast-growing and
      easily breakable palmlike structures to form, which when broken off may form
      secondary nuclei. We propose that thunderstorms, both terrestrial and on other
      planets, and lightning in the solar nebula are instances of such runaway charging
      arising from this nonlinear dynamics in self-replicating granular matter. 

PMID- 24041222
TI  - Nursing home staff's views on residents' dignity: a qualitative interview study.
AB  - BACKGROUND: Maintaining dignity is an important element of end-of-life care and
      also of the care given in nursing homes. Factors influencing personal dignity
      have been studied from both nursing home residents' and staff's perspective.
      Little is however known about the way nursing home staff perceive and promote the
      personal dignity of individual residents in daily practice, or about staff's
      experiences with preserving dignity within the nursing home. The aim of this
      study is to gain more insight in this. METHODS: A qualitative descriptive
      interview study was designed, in which in-depth interviews were performed with 13
      physicians and 15 nurses. They expressed their views on the personal dignity of
      30 recently admitted nursing home residents on the general medical wards of four
      nursing homes in The Netherlands. Interviews were transcribed and analyzed
      following the principles of thematic analysis. RESULTS: According to both
      physicians and nurses, physical impairment and being dependent on others
      threatened the residents' dignity. Whether or not this led to a violation of an
      individual resident's dignity, depended--in staff's opinion--on the resident's
      ability to show resilience and to keep his/her individuality. Staff mentioned
      treating residents with respect and taking care of their privacy as most
      important elements of dignity-conserving care and strived to treat the residents
      as they would like to be treated themselves. They could often mention aspects
      that were important for a particular resident's dignity. But, when asked what
      they could contribute to a particular resident's dignity, they often mentioned
      general aspects of dignity-conserving care, which could apply to most nursing
      home residents. By attempting to give dignity-conserving care, physicians and
      nurses often experienced conflicting values in daily care and barriers caused by
      the lack of resources. CONCLUSIONS: Tailoring dignity-conserving care to an
      individual nursing home resident appears hard to bring about in daily practice.
      Both attention to solve contextual barriers within the nursing home as well as
      more awareness of staff members for their own values, which they take as a
      reference point in treating residents, is needed to promote personal dignity in
      the nursing home setting.

PMID- 24041223
TI  - Impact of mean platelet volume on the occurrence and severity of sudden
      sensorineural hearing loss.
AB  - OBJECTIVE: We aimed to determine: (1) whether mean platelet volume was elevated
      in patients with sudden sensorineural hearing loss, compared with healthy
      controls; and (2) whether mean platelet volume level was related to hearing loss
      severity. MATERIALS AND METHODS: The study included 31 patients with sudden
      sensorineural hearing loss and 31 age- and sex-matched, healthy controls.
      Peripheral venous blood samples were taken from subjects and mean platelet volume
      and levels of glucose, total cholesterol, high-density lipoprotein, low-density
      lipoprotein and triglyceride were measured. RESULTS: Mean platelet volume was
      significantly greater in the sudden sensorineural hearing loss group compared
      with the control group. However, there was no significant correlation between
      mean platelet volume level and hearing loss severity. CONCLUSION: Mean platelet
      volume, a determinant of platelet activation, is elevated in patients with sudden
      sensorineural hearing loss. To our knowledge, this is the first report
      investigating mean platelet volume levels in such patients. Our findings
      indirectly support the hypothesis of vascular impairment as a pathogenetic factor
      in sudden sensorineural hearing loss.

PMID- 24041224
TI  - Design of Pt-shell nanoparticles with alloy cores for the oxygen reduction
      reaction.
AB  - We report that the oxygen binding energy of alloy-core@Pt nanoparticles can be
      linearly tuned by varying the alloy-core composition. Using this tuning
      mechanism, we are able to predict optimal compositions for different alloy
      core@Pt nanoparticles. Subsequent electrochemical measurements of ORR activities
      of AuPd@Pt dendrimer-encapsulated nanoparticles (DENs) are in a good agreement
      with the theoretical prediction that the peak of activity is achieved for a 28%
      Au/72% Pd alloy core supporting a Pt shell. Importantly, these findings represent
      an unusual case of first-principles theory leading to nearly perfect agreement
      with experimental results. 

PMID- 24041226
TI  - Detailed study of DNA hairpin dynamics using single-molecule fluorescence
      assisted by DNA origami.
AB  - The dynamics of two DNA hairpins (5'-TCGCCT-A31-AGGCGA-3' and 5'-TCGCCG-A31
      CGGCGA-3') were studied using immobilization-based and diffusion-based single
      molecule fluorescence techniques. The techniques enabled separated and detailed
      investigation of the states and of the transition reactions. Only two states,
      open and closed, were identified from analysis of the FRET histograms; metastable
      states with lifetimes longer than the technique resolution (0.3 ms) were not
      observed. The opening and closing reaction rates were determined directly from
      the FRET time trajectories, and the Gibbs free energies of these states and of
      the transition state were calculated using the Kramer theory. The rates, which
      are undoubtedly of transitions between the fully closed and the fully open states
      and ranged from 2 to 90 s(-1), were lower (~10-fold) than the rates previously
      determined from fluorescence correlation spectroscopy. The heights of the
      barriers for closing were almost identical for the two hairpins. The barrier for
      opening the hairpin with the stronger stem was higher (4.3 kJ/mol) than that for
      the hairpin with the weaker stem, in very good agreement with the difference in
      stability calculated by the nearest-neighbor method. The barrier for closing the
      hairpin decreased (~8 kJ/mol) and the barrier for opening increased (~4 kJ/mol)
      with increasing NaCl concentration (10-100 mM), indicating that higher ionic
      strength stabilizes the folded state with respect to the transition state and
      stabilizes the transition state relative to the unfolded state. The very good
      agreements in the dynamics measured for free hairpins, for hairpins anchored to
      origami, and for hairpins anchored to the coverslip and the very good agreement
      between the two single-molecule techniques demonstrate that neither the origami
      nor the coverslip influence the hairpin dynamics, supporting a previous
      demonstration that origami can serve as a platform for biophysical
      investigations. 

PMID- 24041225
TI  - Breast cancer receptor status and stage at diagnosis in over 1,200 consecutive
      public hospital patients in Soweto, South Africa: a case series.
AB  - INTRODUCTION: Estimates of the proportion of estrogen receptor negative (ERN) and
      triple-negative (TRN) breast cancer from sub-Saharan Africa are variable and
      include high values. Large studies of receptor status conducted on non-archival
      tissue are lacking from this region. METHODS: We identified 1218 consecutive
      women (91% black) diagnosed with invasive breast cancer from 2006-2012 at a
      public hospital in Soweto, South Africa. Immunohistochemistry based ER,
      progesterone receptor (PR) and human epidermal factor 2 (HER2) receptors were
      assessed at diagnosis on pre-treatment biopsy specimens. Mutually adjusted
      associations of receptor status with stage, age, and race were examined using
      risk ratios (RRs). ER status was compared with age-stratified US Surveillance
      Epidemiology and End Results program (SEER) data. RESULTS: 35% (95% confidence
      interval (CI): 32-38) of tumors were ERN, 47% (45-52) PRN, 26% (23-29) HER2P and
      21% (18-23) TRN. Later stage tumors were more likely to be ERN and PRN (RRs 1.9
      (1.1-2.9) and 2.0 (1.3-3.1) for stage III vs. I) but were not strongly associated
      with HER2 status. Age was not strongly associated with ER or PR status, but older
      women were less likely to have HER2P tumors (RR, 0.95 (0.92-0.99) per 5 years).
      During the study, stage III + IV tumors decreased from 66% to 46%. In black women
      the percentage of ERN (37% (34-40)) and PRN tumors (48% (45-52)) was higher than
      in non-black patients (22% (14-31) and 34% (25-44), respectively, P = 0.004 and P
      = 0.02), which remained after age and stage adjustment. Age-specific ERN
      proportions in black South African women were similar to those of US black women,
      especially for women diagnosed over age 50. CONCLUSION: Although a greater
      proportion of black than non-black South African women had ER-negative or TRN
      breast cancer, in all racial groups in this study breast cancer was predominantly
      ER-positive and was being diagnosed at earlier stages over time. These
      observations provide initial indications that late-stage aggressive breast
      cancers may not be an inherent feature of the breast cancer burden across Africa.

PMID- 24041227
TI  - Improving computer usage for students with physical disabilities through a
      collaborative approach: a pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of an assistive
      technology (AT) intervention to improve the use of available computers as
      assistive technology in educational tasks for students with physical disabilities
      during an ongoing school year. METHODS: Fifteen students (aged 12-18) with
      physical disabilities, included in mainstream classrooms in Sweden, and their
      teachers took part in the intervention. Pre-, post-, and follow-up data were
      collected with Goal Attainment Scaling (GAS), a computer usage diary, and with
      the Psychosocial Impact of Assistive Devices Scale (PIADS). Teachers' opinions of
      goal setting were collected at follow-up. RESULTS: The intervention improved the
      goal-related computer usage in educational tasks and teachers reported they would
      use goal setting again when appropriate. At baseline, students reported a
      positive impact from computer usage with no differences over time regarding the
      PIADS subscales independence, adaptability, or self-esteem. DISCUSSION: The AT
      intervention showed a positive effect on computer usage as AT in mainstream
      schools. Some additional support to teachers is recommended as not all students
      improved in all goal-related computer usage. A clinical implication is that
      students' computer usage can be improved and collaboratively established computer
      based strategies can be carried out by teachers in mainstream schools.

PMID- 24041228
TI  - Intracellular expression of inflammatory proteins S100A8 and S100A9 leads to
      epithelial-mesenchymal transition and attenuated aggressivity of breast cancer
      cells.
AB  - S100 inflammatory proteins have been previously shown to modulate breast cancer
      processes. More specifically, genome-wide transcriptome studies associate S100A8
      and S100A9 members to breast cancer progression and malignancy. Findings have
      shown that S100A8 and S100A9 can signal and regulate cancer cell behavior through
      both extracellular and intracellular-initiated cascades. However, functional
      studies exploring the effects of S100 proteins are often contradictory leaving
      ambiguity and a paucity of data relating to the specific function of S100A8 and
      S100A9 in breast cancer progression. In this study we sought to better define the
      functions of intracellular expressed S100A8 and S100A9 on key signaling and
      cellular processes driving breast cancer malignancy. We observed that
      extracellular treatments of the MCF7 breast cancer cell line with S100A8 and
      S100A9 proteins induces cell proliferation. In contrast, intracellular
      recombinant expression of S100A8 and S100A9 led to growth suppression.
      Furthermore our analysis revealed that intracellular-expressed S100A8 and S100A9
      promote an epithelial-like phenotype through the induction of key markers, such
      as Ecadherin, integrin alpha-5 and Zona Occludens 1 (ZO-1). Concomitantly, S100A8
      and S100A9 negatively regulate the activity of the promalignant Focal Adhesion
      Kinase-1 (FAK) signaling cascade leading to changes in cell adhesion and invasion
      properties. Our results uncover important differences in intracellular versus
      extracellular initiated S100A8 and S100A9 signaling cascades and their effects on
      mammary epithelial growth. Importantly, S100A8 and S100A9 appear to suppress
      breast cancer malignancy through an increase in mesenchymal to epithelial
      transitioning. Our findings shed insight into S100 protein involvement in breast
      cancer invasiveness and metastasis and clarify some of the controversies relating
      to these proteins in breast cancer processes. 

PMID- 24041229
TI  - The interaction between FAK, MYCN, p53 and Mdm2 in neuroblastoma.
AB  - Neuroblastoma tumorigenesis and malignant transformation is driven by
      overexpression and dominance of cell survival pathways and a lack of normal
      cellular senescence or apoptosis. Therefore, manipulation of cell survival
      pathways may decrease the malignant potential of these tumors and provide avenues
      for the development of novel therapeutics. This review focuses on the individual
      protein tyrosine kinase, focal adhesion kinase (FAK) and its interaction with the
      transcription factors, MYCN, p53, and Mdm2, and how their interactions modulate
      the growth and malignancy of neuroblastomas. 

PMID- 24041230
TI  - Treating co-occurring depression and anxiety: modeling the dynamics of
      psychopathology and psychotherapy using the time-varying effect model.
AB  - OBJECTIVE: We demonstrate the utility of the time-varying effect model (TVEM) for
      the analysis of psychotherapy data, with the aim of elucidating complex patterns
      of change over time and dynamic associations between constructs of interest.
      Specifically, we examine the association between depression and co-occurring
      anxiety in a sample of adults treated with interpersonal psychotherapy (IPT) for
      depression or a variant designed to address both depression and co-occurring
      anxiety (IPT-PS, IPT for depression with panic and anxiety symptoms). METHOD:
      Seventy-eight (82% female) adult outpatients with major depression and co
      occurring anxiety were assessed at each of 16 outpatient treatment sessions using
      the Hamilton rating scales for depression and anxiety. RESULTS: On average,
      depressive symptoms declined in a quadratic form over the course of treatment.
      While the association between anxiety and depression was modest early in
      treatment, it strengthened over the middle and latter treatment phases. Finally,
      exploratory analyses suggest that while IPT and IPT-PS were similarly effective
      in reducing depressive symptoms, IPT-PS may be more effective at uncoupling the
      association between core anxiety and depressive symptoms. CONCLUSIONS: Findings
      point to the utility of the TVEM for psychotherapy research and the importance of
      assessing anxiety in the course of treating depression, especially following the
      initial phase of treatment (i.e., after Session 5).

PMID- 24041231
TI  - An adaptive approach for identifying cocaine dependent patients who benefit from
      extended continuing care.
AB  - OBJECTIVE: Study tested whether cocaine dependent patients using cocaine or
      alcohol at intake or in the first few weeks of intensive outpatient treatment
      would benefit more from extended continuing care than patients abstinent during
      this period. The effect of incentives for continuing care attendance was also
      examined. METHOD: Participants (N = 321) were randomized to treatment as usual
      (TAU), TAU and telephone monitoring and counseling (TMC), or TAU and TMC plus
      incentives (TMC+). The primary outcomes were (a) abstinence from all drugs and
      heavy alcohol use and (b) cocaine urine toxicology. Follow-ups were at 3, 6, 9,
      12, 18, and 24 months. RESULTS: Cocaine and alcohol use at intake or early in
      treatment predicted worse outcomes on both measures (ps <= .0002). Significant
      effects favoring TMC over TAU on the abstinence composite were obtained in
      participants who used cocaine (odds ratio [OR] = 1.95 [1.02, 3.73]) or alcohol
      (OR = 2.47 [1.28, 4.78]) at intake or early in treatment. A significant effect
      favoring TMC+ over TAU on cocaine urine toxicology was obtained in those using
      cocaine during that period (OR = 0.55 [0.31, 0.95]). Conversely, there were no
      treatment effects in participants abstinent at baseline and no overall treatment
      main effects. Incentives almost doubled the number of continuing care sessions
      received but did not further improve outcomes. CONCLUSION: An adaptive approach
      for cocaine dependence in which extended continuing care is provided only to
      patients who are using cocaine or alcohol at intake or early in treatment
      improves outcomes in this group while reducing burden and costs in lower risk
      patients.

PMID- 24041233
TI  - Two-year course of generalized anxiety disorder, social anxiety disorder, and
      panic disorder in a longitudinal sample of African American adults.
AB  - OBJECTIVE: Anxiety disorders are the most common group of psychiatric disorders
      in adults. In addition to high prevalence, anxiety disorders are associated with
      significant functional impairment, and published research has consistently found
      them to have a chronic course. To date, very little research has explored the
      clinical characteristics and prospective course of anxiety disorders in racial
      and ethnic minority samples. The aims of this article are to present clinical and
      demographic characteristics at intake and prospective 2-year course findings in a
      sample of African American adults. METHOD: Data are presented from 152 African
      Americans diagnosed with generalized anxiety disorder (GAD, n = 94), social
      anxiety disorder (SAD, n = 85), and panic disorder with agoraphobia (PDA, n = 77)
      who are participating in the Harvard/Brown Anxiety Research Project-Phase II
      (HARP-II). HARP-II is an observational, prospective, longitudinal study of the
      course of anxiety disorders. Participants were interviewed at intake and annually
      for 2 years of follow-up. Probabilities of recovery over 2 years of follow-up
      were calculated using standard survival analysis methods. RESULTS AND
      CONCLUSIONS: Survival analyses revealed a chronic course for all anxiety
      disorders, with rates of recovery of 0.23, 0.07, and 0.00 over 2 years for GAD,
      SAD, and PDA, respectively. These rates of recovery were lower than those
      reported in predominantly non-Latino White longitudinal samples, especially for
      SAD and PDA, suggesting that anxiety disorders may have a more chronic course for
      African Americans, with increased psychosocial impairment and high rates of
      comorbid Axis-I disorders. Clinical implications of these findings are discussed.

PMID- 24041234
TI  - Semisynthesis of mallotus B from rottlerin: evaluation of cytotoxicity and
      apoptosis-inducing activity.
AB  - Mallotus B (2d) is a prenylated dimeric phloroglucinol compound isolated from
      Mallotus philippensis. There have been no reports on the synthesis or biological
      activity of this compound. In the present paper, a semisynthetic preparation of
      mallotus B is reported via base-mediated intramolecular rearrangement of
      rottlerin (1), which is one of the major constituents of M. philippensis. The
      homodimer "rottlerone" was also formed as one of the products of this base
      mediated intramolecular reaction. Rottlerin (1), along with rottlerone (2c) and
      mallotus B (2d), was evaluated for cytotoxicity against a panel of cancer cell
      lines including HEPG2, Colo205, MIAPaCa-2, PC-3, and HL-60 cells. Mallotus B (2d)
      displayed cytotoxicity for MIAPaCa-2 and HL-60 cells with IC50 values of 9 and 16
      MUM, respectively. Microscopic studies in HL-60 cells indicated that mallotus B
      (2d) induces cell cycle arrest at the G1 phase and causes defective cell
      division. It also induces apoptosis, as evidenced by distinct changes in cell
      morphology.

PMID- 24041235
TI  - Computation in the cerebellum.

PMID- 24041237
TI  - Improved ReaxFF force field parameters for Au-S-C-H systems.
AB  - Evaluation and reparameterization of previously reported ReaxFF parameters
      (Jarvi, T. T.; et al. J. Phys. Chem. A 2011, 115, 10315-10322) is carried out for
      Au-S-C-H systems. Changes in Au-S and Au-Au bond parameters and S-Au-S angle
      bending parameters yield improvements for bond bending potential energy surfaces.
      The new ReaxFF parameters lead to good agreement with density functional theory
      geometries of small clusters and gold-thiolate nanoparticles. The energies of
      Au38(SCH3)24 clusters are compared, and the new ReaxFF calculations are also in
      good agreement with PBE calculations for the isomer orderings. In addition, the
      relative energies of Au40(SCH3)24 nanoparticles and Au-thiolate SAMs are
      calculated using the updated parameters. These new ReaxFF parameters will enable
      the study of the geometries and reactivity of larger gold-thiolate nanoparticles.

PMID- 24041236
TI  - Monozygotic twin sisters discordant for familial hemiplegic migraine.
AB  - BACKGROUND: The high concordance rate of migraine in monozygotic twin pairs has
      long been recognised. In the current study, we present a monozygotic twin pair
      discordant for familial hemiplegic migraine (FHM). CASE PRESENTATIONS: We
      evaluated 12 adult family members in 2012. The twin pair was separately examined
      by neurologists at different time points. Mutation screening was performed for
      known FHM-related genes. The monozygosity of the twins was verified. Eleven
      individuals had a history of migraine or paroxysmal neurological symptoms,
      including four patients with motor aura. No mutations were detected in the
      CACNA1A, ATP1A2, SCN1A, PRRT2 or NOTCH3 genes. The monozygotic twin sisters, aged
      52, were discordant for age of onset, motor aura and neuropsychological aura
      (forced thinking). Overall, the family members presented a wide range of
      phenotypical features. CONCLUSIONS: Familial hemiplegic migraine is a monogenic
      disorder that is distinct from migraine with typical aura. However, in certain
      families with motor aura, such as this one, it is possible that the most severe
      phenotype is caused by an unlikely combination of polygenic traits and non
      genetic factors. In these kindreds, we propose that hemiplegic aura is only a
      severe and complex form of typical aura.

PMID- 24041238
TI  - Enhanced anisotropic effective g factors of an Al0.25Ga0.75N/GaN heterostructure
      based quantum point contact.
AB  - Gate-defined quantum point contacts (QPCs) were fabricated with Al0.25Ga0.75N/GaN
      heterostructures grown by metal-organic chemical vapor deposition (MOCVD). In the
      transport study of the Zeeman effect, greatly enhanced effective g factors (g*)
      were obtained. The in-plane g* is found to be 5.5 +/- 0.6, 4.8 +/- 0.4, and 4.2
      +/- 0.4 for the first to the third subband, respectively. Similarly, the out-of
      plane g* is 8.3 +/- 0.6, 6.7 +/- 0.7, and 5.1 +/- 0.7. Increasing g* with the
      population of odd-numbered spin-splitted subbands are obtained at 14 T. This
      portion of increase is assumed to arise from the exchange interaction in one
      dimensional systems. A careful analysis shows that not only the exchange
      interaction but the spin-orbit interaction (SOI) in the strongly confined QPC
      contributes to the enhancement and anisotropy of g* in different subbands. An
      approach to distinguish the respective contributions from the SOI and exchange
      interaction is therefore proposed. 

PMID- 24041241
TI  - Frontiers in solid-state NMR technology.

PMID- 24041239
TI  - Mechanistic basis for high stereoselectivity and broad substrate scope in the
      (salen)Co(III)-catalyzed hydrolytic kinetic resolution.
AB  - In the (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal
      epoxides, the rate- and stereoselectivity-determining epoxide ring-opening step
      occurs by a cooperative bimetallic mechanism with one Co(III) complex acting as a
      Lewis acid and another serving to deliver the hydroxide nucleophile. In this
      paper, we analyze the basis for the extraordinarily high stereoselectivity and
      broad substrate scope observed in the HKR. We demonstrate that the
      stereochemistry of each of the two (salen)Co(III) complexes in the rate
      determining transition structure is important for productive catalysis: a
      measurable rate of hydrolysis occurs only if the absolute stereochemistry of each
      of these (salen)Co(III) complexes is the same. Experimental and computational
      studies provide strong evidence that stereochemical communication in the HKR is
      mediated by the stepped conformation of the salen ligand, and not the shape of
      the chiral diamine backbone of the ligand. A detailed computational analysis
      reveals that the epoxide binds the Lewis acidic Co(III) complex in a well-defined
      geometry imposed by stereoelectronic rather than steric effects. This insight
      serves as the basis of a complete stereochemical and transition structure model
      that sheds light on the reasons for the broad substrate generality of the HKR. 

PMID- 24041242
TI  - In situ solid-state NMR spectroscopy of electrochemical cells: batteries,
      supercapacitors, and fuel cells.
AB  - Electrochemical cells, in the form of batteries (or supercapacitors) and fuel
      cells, are efficient devices for energy storage and conversion. These devices
      show considerable promise for use in portable and static devices to power
      electronics and various modes of transport and to produce and store electricity
      both locally and on the grid. For example, high power and energy density lithium
      ion batteries are being developed for use in hybrid electric vehicles where they
      improve the efficiency of fuel use and help to reduce greenhouse gas emissions.
      To gain insight into the chemical reactions involving the multiple components
      (electrodes, electrolytes, interfaces) in the electrochemical cells and to
      determine how cells operate and how they fail, researchers ideally should employ
      techniques that allow real-time characterization of the behavior of the cells
      under operating conditions. This Account reviews the recent use of in situ solid
      state NMR spectroscopy, a technique that probes local structure and dynamics, to
      study these devices. In situ NMR studies of lithium-ion batteries are performed
      on the entire battery, by using a coin cell design, a flat sealed plastic bag, or
      a cylindrical cell. The battery is placed inside the NMR coil, leads are
      connected to a potentiostat, and the NMR spectra are recorded as a function of
      state of charge. (7)Li is used for many of these experiments because of its high
      sensitivity, straightforward spectral interpretation, and relevance to these
      devices. For example, (7)Li spectroscopy was used to detect intermediates formed
      during electrochemical cycling such as LixC and LiySiz species in batteries with
      carbon and silicon anodes, respectively. It was also used to observe and quantify
      the formation and growth of metallic lithium microstructures, which can cause
      short circuits and battery failure. This approach can be utilized to identify
      conditions that promote dendrite formation and whether different electrolytes and
      additives can help prevent dendrite formation. The in situ method was also
      applied to monitor (by (11)B NMR) electrochemical double-layer formation in
      supercapacitors in real time. Though this method is useful, it comes with
      challenges. The separation of the contributions from the different cell
      components in the NMR spectra is not trivial because of overlapping resonances.
      In addition, orientation-dependent NMR interactions, including the spatial- and
      orientation-dependent bulk magnetic susceptibility (BMS) effects, can lead to
      resonance broadening. Efforts to understand and mitigate these BMS effects are
      discussed in this Account. The in situ NMR investigation of fuel cells initially
      focused on the surface electrochemistry at the electrodes and the electrochemical
      oxidation of methanol and CO to CO2 on the Pt cathode. On the basis of the (13)C
      and (195)Pt NMR spectra of the adsorbates and electrodes, CO adsorbed on Pt and
      other reaction intermediates and complete oxidation products were detected and
      their mode of binding to the electrodes investigated. Appropriate design and
      engineering of the NMR hardware has allowed researchers to integrate intact
      direct methanol fuel cells into NMR probes. Chemical transformations of the
      circulating methanol could be followed and reaction intermediates could be
      detected in real time by either (2)H or (13)C NMR spectroscopy. By use of the in
      situ NMR approach, factors that control fuel cell performance, such as methanol
      cross over and catalyst performance, were identified. 

PMID- 24041244
TI  - An overview of the last 10 years of genetically engineered crop safety research.
AB  - The technology to produce genetically engineered (GE) plants is celebrating its
      30th anniversary and one of the major achievements has been the development of GE
      crops. The safety of GE crops is crucial for their adoption and has been the
      object of intense research work often ignored in the public debate. We have
      reviewed the scientific literature on GE crop safety during the last 10 years,
      built a classified and manageable list of scientific papers, and analyzed the
      distribution and composition of the published literature. We selected original
      research papers, reviews, relevant opinions and reports addressing all the major
      issues that emerged in the debate on GE crops, trying to catch the scientific
      consensus that has matured since GE plants became widely cultivated worldwide.
      The scientific research conducted so far has not detected any significant hazards
      directly connected with the use of GE crops; however, the debate is still
      intense. An improvement in the efficacy of scientific communication could have a
      significant impact on the future of agricultural GE. Our collection of scientific
      records is available to researchers, communicators and teachers at all levels to
      help create an informed, balanced public perception on the important issue of GE
      use in agriculture.

PMID- 24041243
TI  - Membrane protein structure determination in membrana.
AB  - The two principal components of biological membranes, the lipid bilayer and the
      proteins integrated within it, have coevolved for specific functions that mediate
      the interactions of cells with their environment. Molecular structures can
      provide very significant insights about protein function. In the case of membrane
      proteins, the physical and chemical properties of lipids and proteins are highly
      interdependent; therefore structure determination should include the membrane
      environment. Considering the membrane alongside the protein eliminates the
      possibility that crystal contacts or detergent molecules could distort protein
      structure, dynamics, and function and enables ligand binding studies to be
      performed in a natural setting. Solid-state NMR spectroscopy is compatible with
      three-dimensional structure determination of membrane proteins in phospholipid
      bilayer membranes under physiological conditions and has played an important role
      in elucidating the physical and chemical properties of biological membranes,
      providing key information about the structure and dynamics of the phospholipid
      components. Recently, developments in the recombinant expression of membrane
      proteins, sample preparation, pulse sequences for high-resolution spectroscopy,
      radio frequency probes, high-field magnets, and computational methods have
      enabled a number of membrane protein structures to be determined in lipid bilayer
      membranes. In this Account, we illustrate solid-state NMR methods with examples
      from two bacterial outer membrane proteins (OmpX and Ail) that form integral
      membrane beta-barrels. The ability to measure orientation-dependent frequencies
      in the solid-state NMR spectra of membrane-embedded proteins provides the
      foundation for a powerful approach to structure determination based primarily on
      orientation restraints. Orientation restraints are particularly useful for NMR
      structural studies of membrane proteins because they provide information about
      both three-dimensional structure and the orientation of the protein within the
      membrane. When combined with dihedral angle restraints derived from analysis of
      isotropic chemical shifts, molecular fragment replacement, and de novo structure
      prediction, orientation restraints can yield high-quality three-dimensional
      structures with few or no distance restraints. Using complementary solid-state
      NMR methods based on oriented sample (OS) and magic angle spinning (MAS)
      approaches, one can resolve and assign multiple peaks through the use of
      (15)N/(13)C labeled samples and measure precise restraints to determine
      structures. 

PMID- 24041245
TI  - Preventing academic difficulties in preterm children: a randomised controlled
      trial of an adaptive working memory training intervention - IMPRINT study.
AB  - BACKGROUND: Very preterm children exhibit difficulties in working memory, a key
      cognitive ability vital to learning information and the development of academic
      skills. Previous research suggests that an adaptive working memory training
      intervention (Cogmed) may improve working memory and other cognitive and
      behavioural domains, although further randomised controlled trials employing long
      term outcomes are needed, and with populations at risk for working memory
      deficits, such as children born preterm.In a cohort of extremely preterm (<28
      weeks' gestation)/extremely low birthweight (<1000 g) 7-year-olds, we will assess
      the effectiveness of Cogmed in improving academic functioning 2 years' post
      intervention. Secondary objectives are to assess the effectiveness of Cogmed in
      improving working memory and attention 2 weeks', 12 months' and 24 months' post
      intervention, and to investigate training related neuroplasticity in working
      memory neural networks 2 weeks' post-intervention. METHODS/DESIGN: This double
      blind, placebo-controlled, randomised controlled trial aims to recruit 126
      extremely preterm/extremely low birthweight 7-year-old children. Children
      attending mainstream school without major intellectual, sensory or physical
      impairments will be eligible. Participating children will undergo an extensive
      baseline cognitive assessment before being randomised to either an adaptive or
      placebo (non-adaptive) version of Cogmed. Cogmed is a computerised working memory
      training program consisting of 25 sessions completed over a 5 to 7 week period.
      Each training session takes approximately 35 minutes and will be completed in the
      child's home. Structural, diffusion and functional Magnetic Resonance Imaging,
      which is optional for participants, will be completed prior to and 2 weeks
      following the training period. Follow-up assessments focusing on academic skills
      (primary outcome), working memory and attention (secondary outcomes) will be
      conducted at 2 weeks', 12 months' and 24 months' post-intervention. DISCUSSION:
      To our knowledge, this study will be the first randomised controlled trial to (a)
      assess the effectiveness of Cogmed in school-aged extremely preterm/extremely low
      birthweight children, while incorporating advanced imaging techniques to
      investigate neural changes associated with adaptive working memory training, and
      (b) employ long-term follow-up to assess the potential benefit of improved
      working memory on academic functioning. If effective, Cogmed would serve as a
      valuable, available intervention for improving developmental outcomes for this
      population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12612000124831.

PMID- 24041246
TI  - Accelerated calcium phosphate cement degradation due to incorporation of glucono
      delta-lactone microparticles.
AB  - Injectable calcium phosphate cements (CPC) are frequently used for filling of
      bone defects due to their excellent osteocompatibility. Their poor degradability,
      however, limits complete regeneration of bone defects. Organic additives that
      produce acid by-products are particularly attractive to create macroporosity in
      situ since CPC degrade by acid dissolution. The aim of the current study was to
      investigate whether glucono-delta-lactone (GDL) can be used as acid-producing
      microparticles for incorporation into CPC without compromising its
      osteocompatibility. Characterization studies confirmed that CPCs containing
      either low or high amounts of GDL were injectable and self-setting, while a
      considerable amount of porosity was formed already within 1 day of incubation in
      phosphate buffered saline due to dissolution of GDL. Histomorphometrical
      evaluation after 2 weeks of implantation revealed that CPC containing 10% of GDL
      degraded faster and was replaced by more bone tissue than CPCs containing either
      Poly (lactic-co-glycolic acid) (PLGA) or gelatin microspheres. Summarizing, the
      current study showed that CPCs containing appropriate amounts of GDL display
      accelerated degradation and new bone formation compared with CPCs containing
      microparticles made of conventional polymers such as PLGA or gelatin. 

PMID- 24041247
TI  - The expression of glycosaminoglycans and proteoglycans in the uterine cervix of
      albino rats after local hyaluronidase infusion.
AB  - OBJECTIVE: To assess the local effect of hyaluronidase injection on the
      expression of glycosaminoglycans (GAGs) and proteoglycans (PGs) in the
      extracellular matrix of the uterine cervix from pregnant albino rats. METHODS:
      Ten pregnant rats were divided into two groups on day 18 of pregnancy. The
      experimental group (Gexp) of rats received an intracervical infusion of 0.02 mL
      of hyaluronidase diluted to 1 mL with distilled water, whereas the control group
      (Gc) received 1 mL of distilled water. On day 20 of pregnancy, the pregnant rats
      were sacrificed and the uterine cervixes from all rats were then dissected. The
      qualitative expression of hyaluronic acid (HA) was assessed by
      immunohistochemistry and quantified by sandwich ELISA. To compare the
      quantitative GAG values between groups, a Student's t-test for independent
      samples was performed. PGs were also assessed by immunohistochemical analysis.
      RESULTS: The electrophoretic profile of newly synthesized radioactively labeled
      GAGs degraded by specific enzymes showed that there were two predominant GAGs in
      both Gc and Gexp, i.e. heparan sulfate (HS) and a mixture of hondroitin sulfate
      (CS) and dermatan sulfate (DS). The concentrations of GAGs showed a significant
      reduction of CS/DS (p < 0.004) and HS (p < 0.005) relative to Gc. HA staining was
      less intense in the lamina propria and area surrounding the blood vessels in Gexp
      compared to Gc. The HA contents were also significantly reduced (p < 0.012).
      CONCLUSIONS: Intracervical hyaluronidase infusion promoted a significant
      reduction in the concentration of sulfated GAGs as assessed by both qualitative
      (histochemical) and quantitative (fluorometric) measurements of HA.

PMID- 24041248
TI  - Interspecies interaction extends bacterial survival at solid-air interfaces.
AB  - Despite the ubiquity of biofilms in natural and man-made environments, research
      on surface-associated cells has focused primarily on solid-liquid interfaces.
      This study evaluated the extent to which bacterial cells persist on inanimate
      solid-air interfaces. The desiccation tolerance of bacterial strains isolated
      from indoor air, as well as of a test strain (Pseudomonas aeruginosa), was
      determined at different levels of relative humidity (RH) using the large droplet
      inoculation method in an aerosol chamber. The cells survived longer at lower (25
      and 42%) than at high RH (95%). Four of the seven indoor strains selected for
      further study showed extended period of survival following deposition as 0.05-0.1
      ml of washed culture followed by desiccation, each with different effects on the
      survival of the test strain, P. aeruginosa. A strain closely related to
      Arthrobacter species afforded the highest level of protection to the test strain.
      Even though the desiccation-tolerant strains survived when they were deposited as
      bioaerosols, the protective role towards the test strain was not observed when
      the latter was deposited as a bioaerosol. These, which are often-unculturable,
      bacteria may go undetected during routine monitoring of biofouling, thereby
      allowing them to act as reservoirs and extending the habitat range of undesired
      microorganisms. 

PMID- 24041249
TI  - Pain-related fear of movement and catastrophizing in whiplash-associated
      disorders.
AB  - OBJECTIVE: The main aim of this study was to test whether pain-related fear of
      movement and catastrophizing were predictors of pain intensity and disability 6
      months after a whiplash injury. The mediator role of fear of movement was also
      explored. A sample of 147 whiplash patients with neck pain for less than 3 months
      participated in the first assessment, and 123 of them were interviewed again at a
      6-month follow-up. Multiple regression analyses were performed. RESULTS: Fear of
      movement, initial pain intensity and initial disability were independent
      predictors of disability at the 6-month follow-up. Initial pain intensity and
      initial pain duration were significant predictors of pain intensity at 6 months.
      Fear of movement was found not to be a mediator in either of the 2 outcomes at
      the 6-month follow-up. CONCLUSIONS: These findings suggest that interventions
      designed to reduce the impact of injury severity and pain-related fear of
      movement after a motor vehicle accident may be relevant for preventing long
      lasting symptoms.

PMID- 24041250
TI  - Promoting exercise maintenance: how interventions with booster sessions improve
      long-term rehabilitation outcomes.
AB  - OBJECTIVE: Follow-up intervention boosters are supposed to promote exercise
      maintenance beyond initial treatment. The current quasi-experimental study
      investigated the benefits of adding telephone-delivered intervention boosters to
      a self-management exercise intervention for rehabilitants. Psycho-social
      mechanisms by which the intervention boosters promote exercise maintenance were
      examined. RESEARCH DESIGN: Between 2009 and 2011, individuals in cardiac and
      orthopedic rehabilitation (N = 1,166) were allocated to either a self-management
      exercise intervention or a control group (i.e., questionnaire only). In addition
      to standard rehabilitation, participants in the intervention group were offered a
      series of telephone-delivered intervention boosters after 6 weeks and again after
      6 months. Self-efficacy, action planning, and satisfaction with previous exercise
      outcomes were reassessed 12 months after discharge. Habit strength and exercise
      were measured 18 months after rehabilitation. RESULTS: The intervention with
      boosters promoted the maintenance of planning, self-efficacy, satisfaction,
      exercise, and habit strength. Changes in exercise were simultaneously mediated by
      changes in planning, self-efficacy, and satisfaction. Changes in habit strength
      were sequentially mediated by planning and exercise. CONCLUSIONS: Interventions
      with boosters that focus on action planning, self-efficacy, and satisfaction help
      to maintain self-directed postrehabilitation exercise. Frequent exercise
      performance, in turn, can strengthen exercise habits.

PMID- 24041251
TI  - Clinical utility of the Behavior Rating Inventory of Executive Function-Self
      Report (BRIEF-SR) in adolescents with traumatic brain injury.
AB  - OBJECTIVE: To evaluate the factor structure and correlates of the Behavior Rating
      Inventory of Executive Function-Self-Report (BRIEF-SR) in 118 adolescents with
      traumatic brain injury (TBI). METHOD: Cross-sectional study. Maximum-likelihood
      exploratory, as well as confirmatory, factor analysis. External correlates of
      factor scores were evaluated. RESULTS: Two latent constructs were identified,
      with notable variation in scale loading pattern compared with standardization
      sample findings of the BRIEF-SR. These factors covaried inversely with severity
      of TBI; more severe injuries were associated with lower self-ratings of executive
      dysfunction, indicating a possible lack of deficit awareness in those with
      relatively severe injuries. Premorbid ADHD affected both factors, resulting in
      higher self-ratings of executive dysfunction, suggesting preserved awareness of
      preexisting difficulties in those with uncomplicated mild injuries. In addition,
      males reported less executive dysfunction than females. CONCLUSIONS/IMPLICATIONS:
      Findings suggest that the BRIEF-SR measures somewhat different latent constructs
      after TBI than in typically developing adolescents, and that BRIEF-SR scores need
      to be considered in concert with objective measures of injury severity and
      premorbid demographic and historical variables. (PsycINFO Database Record (c)
      2013 APA, all rights reserved).

PMID- 24041252
TI  - Structural diversity due to amino alcohol ligands leading to rare MU4-hydroxo
      bridged tetranuclear and "bicapped cubane" cores in copper(II) complexes: a
      theoretical and experimental magnetostructural study.
AB  - The MU4-hydroxo- and alkoxo-bridged tetranuclear copper(II) complexes, [Cu4(MU4
      OH)(dmae)4][Ag(NO3)4] (1), [Cu4(MU4-OH)(dmae)4][Na(NO3)4] (2), [Cu4(MU4
      OH)(dmae)4][K(NO3)4] (3), and hexanuclear alkoxo-bridged "bicapped cubane"
      copper(II) complex [Cu6(ae)8(ClO4)2](ClO4)2.MeOH (8) (dmae = N,N
      dimethylaminoethanolato and ae = 2-aminoethanolato) were synthesized via self
      assembly from chelating amino alcohols and copper(II), silver (1), sodium (2),
      and potassium (3) nitrates or copper(II) perchlorate (8). The complexes are
      characterized by elemental analyses, single-crystal X-ray diffraction, and
      variable temperature magnetic measurements. The crystal structures of complexes 1
      3 consist of almost planar tetranuclear [Cu4(MU4-OH)(dmae)4](3+) units, in which
      Cu(II) ions are also weakly bonded to nitrate anions. The adjacent tetranuclear
      units of 1-3 are connected by ionic interactions between nitrate anions and
      sodium, potassium, or silver cations resulting in the formation of 1D polymers.
      The crystal structure of 8 consists of hexanuclear [Cu6(ae)8](4+) "bicapped
      cubane" units, in which the capping Cu(II) ions are weakly bonded to perchlorate
      anions. The adjacent hexanuclear units of 8 are connected by hydrogen bonds
      resulting in the formation of 3D hydrogen bonded networks. Also the results from
      the synthetic studies leading to the formation of new copper(II) and silver(I)
      complexes (4-7) using Hae, 3-aminopropanol (Hap), and N,N-dimethylaminopropanol
      (Hdmap) in similar reactions, which gave tetra- and hexanuclear complexes, are
      presented. Experimental magnetic studies showed that complexes 1 and 2 exhibit
      dominant antiferromagnetic coupling leading to an S = 0 ground state, whereas 8
      exhibits a large dominant antiferromagnetic interaction between the capping
      copper atoms and the copper atoms of the top and bottom faces of the cubane unit
      that define two isosceles triangles. This interaction leads to an S = 1/2 ground
      state for each triangle. The weak ferromagnetic interaction between these doublet
      states through the cubane unit leads to a triplet S = 1 ground state for 8. The
      values of the magnetic exchange coupling constant were the following: J = +1.8
      (1) and +2.9 cm(-1) (2) between adjacent copper atoms; J' = -29.2 (1) and -32.2
      cm(-1) (2) between opposite copper atoms; J = -297.6 cm(-1) and zJ' = +0.07 cm(
      1) (8). Magnetic coupling constants calculated for 2 and 8 by DFT methods are in
      general of the same nature and magnitude as the experimental ones. 

PMID- 24041253
TI  - Dilution and the theoretical description of growth-rate dependent gene
      expression.
AB  - Expression of a gene is not only tuned by direct regulation, but also affected by
      the global physiological state of the (host) cell. This global dependence
      complicates the quantitative understanding of gene regulation and the design of
      synthetic gene circuits. In bacteria these global effects can often be described
      as a dependence on the growth rate. Here we discuss how growth-rate dependence
      can be incorporated in mathematical models of gene expression by comparing data
      for unregulated genes with the predictions of different theoretical descriptions
      of growth-rate dependence. We argue that a realistic description of growth
      effects requires a growth-rate dependent protein synthesis rate in addition to
      dilution by growth. 

PMID- 24041254
TI  - Effect of PEGylation on controllably spaced adsorption of ferritin molecules.
AB  - The interparticle distance between nanoparticles (NPs) dispersed on on SiO2 was
      shown to be controlled by PEGylation. Ferritins with nanoparticle cores were
      prepared and PEGylated with poly(ethylene glycol)s (PEGs) of two different
      molecular weights. It was shown that the thickness of the PEG layer on the
      ferritin surface determines the interparticle distance under short Debye lengths.
      Under conditions where the Debye length was greater than the PEG layer thickness,
      distance between ferritins increased due to the electrostatic repulsive force.
      Results suggest that the PEG layer accommodated a small amount of counterions
      insufficient to cancel the ferritin outer surface charges. Simulation showed that
      ferritins adsorbed randomly and interparticle distance can be predicted
      theoretically. We demonstrate that PEGylated ferritins, that is, NP cores, can be
      dispersed on a surface with interval distances between particles determined by
      the combination of the ionic strength of the solution and the molecular weight of
      the PEG. 

PMID- 24041255
TI  - Sedimentation of a charged porous particle in a charged cavity.
AB  - The sedimentation of a charged porous sphere at the center of a charged spherical
      cavity filled with an electrolyte solution is analyzed. The thickness of the
      electric double layers around the particle and cavity wall is arbitrary, and
      their relaxation effect is considered. Through the use of a set of linearized
      electrokinetic equations and a perturbation method, the ionic electrochemical
      potential energy, electric potential, and velocity fields in the fluid are solved
      with the fixed space charge density of the particle and surface charge density of
      the cavity as the small perturbation parameters, and an explicit formula for the
      sedimentation velocity is obtained. Due to the electroosmotic enhancement on the
      fluid recirculation in the cavity caused by the sedimentation-induced electric
      field, the presence of the surface charges on the cavity wall increases the
      sedimentation velocity of the porous particle. For the sedimentation of a porous
      particle in a cavity with their fixed charges of the same sign, the effect of
      electric interaction between the particle and cavity wall in general increases
      the sedimentation velocity. For the case of their fixed charges with opposite
      signs, the sedimentation velocity is increased/reduced if the magnitude of the
      fixed charge density of the cavity wall is relatively large/small. The effect of
      the surface charges at the cavity wall on the sedimentation of the porous
      particle increases with an increase in the permeability for fluid flow within the
      particle and with a decrease in the particle-to-cavity radius ratio (i.e., an
      increase in the surface area of the cavity wall relative to a given size of the
      particle, which enhances the fluid recirculation effect). 

PMID- 24041256
TI  - Effect of mastoid drilling on hearing of the contralateral ear.
AB  - OBJECTIVES: This study aimed to: understand the effect that high intensity noise
      associated with drilling (during otological surgery) has on hearing in the
      contralateral ear; determine the nature of hearing loss, if any, by establishing
      whether it is temporary or persistent; and examine the association between
      hearing loss and various drill parameters. METHODS: A prospective clinical study
      was carried out at a tertiary centre. Thirty patients with unilateral
      cholesteatoma and normal contralateral hearing were included. Patients were
      evaluated pre-operatively and for five days following surgery using high
      frequency pure tone audiometry, and low and high frequency transient evoked and
      distortion product otoacoustic emission testing. RESULTS: The findings revealed
      statistically significant changes in distortion product otoacoustic emissions at
      high frequencies (p = 0.016), and in transient evoked otoacoustic emissions at
      both low and high frequencies (p = 0.035 and 0.021, respectively). There was a
      higher statistical association between otoacoustic emission changes and cutting
      burrs compared with diamond burrs. CONCLUSION: Drilling during mastoid surgery
      poses a threat to hearing in the contralateral ear due to noise and vibration
      conducted transcranially.

PMID- 24041257
TI  - Accurate prostate tumour detection with multiparametric magnetic resonance
      imaging: dependence on histological properties.
AB  - BACKGROUND: To benefit most of focal treatment of prostate tumours, detection
      with high precision of all tumour voxels is needed. Although diffusion-weighted
      imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)
      have good diagnostic performance, perfect tumour detection is challenging. In
      this study, we investigated the variation in prostate tissue characteristics
      Gleason score (GS), cell density (CD) and microvessel density (MVD) to explain
      the limitations in tumour voxel detection with a MRI-based logistic regression
      model. MATERIAL AND METHODS: Twelve radical prostatectomy patients underwent a
      pre-operative 3.0T DWI and DCE-MRI exam. The MRI scans were used to calculate
      voxel-wise tumour probability with a logistic regression model for the peripheral
      zone (PZ) of the prostate. Tumour probability maps were correlated and validated
      with whole-mount histology. Additionally, from the whole-mount histological
      sections CD, MVD and GS were retrieved for every single voxel. GS, CD and MVD of
      true- and false-positive voxels and of true- and false-negative voxels were
      compared using Mann-Whitney U-tests. RESULTS: False-negative tumour voxels had
      significantly lower CD and MVD (p < 0.0001) and were similar to non-tumour PZ.
      True-positive detected tumour voxels had high CDs and MVDs (p < 0.0001). In
      addition, tumour voxels with higher GS showed a trend towards more frequent
      detection (p = 0.06). Tumour voxels with GS >= 3 + 4 showed higher CD and MVD
      compared to tumour voxels with GS 3 + 3 (p < 0.0001). CONCLUSION: Tumour voxels
      with low CD and MVD resemble healthy tissue and are limiting tumour voxel
      detection using DWI and DCE-MRI. Nevertheless, the most aggressive tumour voxels,
      containing high CD, MVD and GS, are more likely to be detected and can therefore
      be treated with high dose using focal therapy or focal boosting.

PMID- 24041258
TI  - FLT1 kinase is a mediator of radioresistance and survival in head and neck
      squamous cell carcinoma.
AB  - Head and neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy
      worldwide, responsible for approximately half a million new cases every year. The
      treatment of this disease is challenging and characterised by high rates of
      therapy failure and toxicity, stressing the need for new innovative treatment
      strategies. MATERIAL AND METHODS: In this study we performed a shRNAmir-based
      screen on HNSCC cells with the aim to identify tyrosine kinases that are
      mediating radiotherapy resistance. RESULTS: The receptor tyrosine kinase FLT1
      (VEGFR1) was identified as an important driver of cell survival and
      radioresistance. We show that FLT1 is phosphorylated in HNSCC cells, and document
      autocrine production of FLT1 ligands VEGFA and VEGFB, leading to receptor
      activation. Immunohistochemistry on HNSCC patient samples demonstrated FLT1 and
      VEGFA to be uniformly expressed. Interestingly, FLT1 was selectively
      overexpressed in tumour tissue as compared to non-cancerous epithelium.
      Remarkably, we found only membrane permeable FLT1 kinase inhibitors to be
      effective, which was in agreement with the intracellular localisation of FLT1.
      DISCUSSION AND CONCLUSION: Taken together, we document expression of FLT1 in
      HNSCC and demonstrate this kinase to modulate radioresistance and cancer cell
      survival. Given the fact that FLT1 kinase is selectively upregulated in tumour
      tissue and that its kinase function seems expendable for normal life and
      development, this kinase holds great promise as a new potential therapeutic
      target.

PMID- 24041259
TI  - Preventing and lessening exacerbations of asthma in school-age children
      associated with a new term (PLEASANT): study protocol for a cluster randomised
      control trial.
AB  - BACKGROUND: Within the UK, during September, there is a pronounced increase in
      the number of unscheduled medical contacts by school-aged children (4-16 years)
      with asthma. It is thought that that this might be caused by the return back to
      school after the summer holidays, suddenly mixing with other children again and
      picking up viruses which could affect their asthma. There is also a drop in the
      number of prescriptions administered in August. It is possible therefore that
      children might not be taking their medication as they should during the summer
      contributing to them becoming ill when they return to school.It is hoped that a
      simple intervention from the GP to parents of children with asthma at the start
      of the summer holiday period, highlighting the importance of maintaining asthma
      medication can help prevent increased asthma exacerbation, and unscheduled NHS
      appointments, following return to school in September. METHODS/DESIGN: PLEASANT
      is a cluster randomised trial. A total of 140 General Practices (GPs) will be
      recruited into the trial; 70 GPs randomised to the intervention and 70 control
      practices of "usual care". An average practice is expected to have approximately
      100 children (aged 4-16 with a diagnosis of asthma) hence observational data will
      be collected on around 14000 children over a 24-month period. The Clinical
      Practice Research Datalink will collect all data required for the study which
      includes diagnostic, prescription and referral data. DISCUSSION: The trial will
      assess whether the intervention can reduce exacerbation of asthma and unscheduled
      medical contacts in school-aged children associated with the return to school
      after the summer holidays. It has the potential to benefit the health and quality
      of life of children with asthma while also improving the effectiveness of NHS
      services by reducing NHS use in one of the busiest months of the year.An
      exploratory health economic analysis will gauge any cost saving associated with
      the intervention and subsequent impacts on quality of life. If results for the
      intervention are positive it is hoped that this could be adopted as part of
      routine care management of childhood asthma in general practice. TRIAL
      REGISTRATION: Current controlled trials: ISRCTN03000938 (assigned 19/10/12)
      http://www.controlled-trials.com/ISRCTN03000938/. UKCRN ID: 13572.

PMID- 24041260
TI  - "Giant surfactants" created by the fast and efficient functionalization of a DNA
      tetrahedron with a temperature-responsive polymer.
AB  - Copper catalyzed azide-alkyne cycloaddition (CuAAC) was employed to synthesize
      DNA block copolymers (DBCs) with a range of polymer blocks including temperature
      responsive poly(N-isoproylacrylamide) (poly(NIPAM)) and highly hydrophobic
      poly(styrene). Exceptionally high yields were achieved at low DNA concentrations,
      in organic solvents, and in the absence of any solid support. The DNA segment of
      the DBC remained capable of sequence-specific hybridization: it was used to
      assemble a precisely defined nanostructure, a DNA tetrahedron, with pendant
      poly(NIPAM) segments. In the presence of an excess of poly(NIPAM) homopolymer,
      the tetrahedron-poly(NIPAM) conjugate nucleated the formation of large, well
      defined nanoparticles at 40  degrees C, a temperature at which the homopolymer
      precipitated from solution. These composite nanoparticles were observed by
      dynamic light scattering and cryoTEM, and their hybrid nature was confirmed by
      AFM imaging. As a result of the large effective surface area of the tetrahedron,
      only very low concentrations of the conjugate were required in order for this
      surfactant-like behavior to be observed. 

PMID- 24041261
TI  - Clinical review: the role of ultrasound in estimating extra-vascular lung water.
AB  - The estimation of extra-vascular lung water (EVLW) is an essential component in
      the assessment of critically ill patients. EVLW is independently associated with
      mortality and its manipulation has been shown to improve outcome. Accurate
      assessment of lung water is possible with CT and MR imaging but these are
      impractical for real-time measurement in sick patients and have been superseded
      by single thermal dilution techniques. While useful, single thermo-dilution
      requires repeated calibration and is prone to error, suggesting a need for other
      monitoring methods. Traditionally the lung was not thought amenable to ultrasound
      examination owing to the high acoustic impedance of air; however, the
      identification of artefacts in diseased lung has led to increased use of
      ultrasound as a point of care investigation for both diagnosis and to monitor
      response to interventions. Following the initial description of B-lines in
      association with increased lung water, accumulating evidence has shown that they
      are a useful and responsive measure of the presence and dynamic changes in EVLW.
      Animal models have confirmed a correlation with lung gravimetry and the utility
      of B-lines has been demonstrated in many clinical situations and correlated
      against other established measures of EVLW. With increasing availability and
      expertise the role of ultrasound in estimating EVLW should be embedded in
      clinical practice and incorporated into clinical algorithms to aid decision
      making. This review looks at the evidence for ultrasound as a valid, easy to use,
      non-invasive point of care investigation to assess EVLW. 

PMID- 24041263
TI  - Neighborhood characteristics, parenting styles, and children's behavioral
      problems in Chinese American immigrant families.
AB  - Using data from a socioeconomically diverse sample of Chinese American children
      (n = 258, aged 6-9 years) in immigrant families, we examined the concurrent
      relations among neighborhood economic disadvantage and concentration of Asian
      residents, parenting styles, and Chinese American children's externalizing and
      internalizing problems. Neighborhood characteristics were measured with 2000 U.S.
      Census tract-level data, parents (mostly mothers) rated their own parenting
      styles, and parents and teachers rated children's behavioral problems. Path
      analysis was conducted to test two hypotheses: (a) parenting styles mediate the
      relations between neighborhood characteristics and children's behavioral
      problems, and (b) children's behavioral problems mediate the relations between
      neighborhood and parenting styles. We found that neighborhood Asian concentration
      was positively associated with authoritarian parenting, which in turn was
      associated with Chinese American children's higher externalizing and
      internalizing problems (by parents' reports). In addition, neighborhood economic
      disadvantage was positively related to children's externalizing problems (by
      parents' reports), which in turn predicted lower authoritative parenting. The
      current results suggest the need to consider multiple pathways in the relations
      among neighborhood, family, and child adjustment, and they have implications for
      the prevention and intervention of behavioral problems in Chinese American
      children.

PMID- 24041264
TI  - Interpersonal suicide risk for American Indians: investigating thwarted
      belongingness and perceived burdensomeness.
AB  - American Indians (AIs) experience increased suicide rates compared with other
      groups in the United States. However, no past studies have examined AI suicide by
      way of a recent empirically supported theoretical model of suicide. The current
      study investigated whether AI suicidal ideation can be predicted by two
      components: thwarted belongingness and perceived burdensomeness, from the
      Interpersonal-Psychological Theory of Suicide (T. E. Joiner, 2005, Why people die
      by suicide. Cambridge, MA: Harvard University Press). One hundred seventy-one AIs
      representing 27 different tribes participated in an online survey. Hierarchical
      regression analyses showed that perceived burdensomeness significantly predicted
      suicidal ideation above and beyond demographic variables and depressive symptoms;
      however, thwarted belongingness did not. Additionally, the two-way interaction
      between thwarted belongingness and perceived burdensomeness significantly
      predicted suicidal ideation. These results provide initial support for continued
      research on the components of the Interpersonal-Psychological Theory of Suicide,
      an empirically supported theoretical model of suicide, to predict suicidal
      ideation among AI populations.

PMID- 24041262
TI  - Susceptibility to myocardial ischemia reperfusion injury at early stage of type 1
      diabetes in rats.
AB  - BACKGROUND: Large body of evidences accumulated in clinical and epidemiological
      studies indicate that hearts of diabetic subjects are more sensitive to ischemia
      reperfusion injury (IRI), which results in a higher rate of mortality at post
      operation than that of non-diabetes. However, experimental results are equivocal
      and point to either increased or decreased susceptibility of the diabetic hearts
      to IRI, especially at the early stage of the disease. The present study was
      designed to test the hypothesis that the duration/severity of the indexed
      ischemia is a major determinant of the vulnerability to myocardial IRI at early
      stage of diabetes. METHODS: Four weeks streptozotocin (STZ)-induced diabetic (D)
      and non-diabetic (C) Sprague-Dawley rats were randomly assigned to receive 30 or
      45 min of left anterior descending artery ligation followed by 2 or 3 hours of
      reperfusion, respectively. Cardiac function was recorded by using Pressure-Volume
      (PV) conduction system. Myocardial infarct size was determined with
      triphenyltetrazolium chloride staining. Plasma Creatine kinase-MB (CK-MB),
      Lactate dehydrogenase (LDH) release, myocardial nitric oxide(NO) content and
      nitrotyrosine formation, 15-F(2t)-Isoprostane and plasma superoxide dismutase
      (SOD) were measured with colorimetric assays. Cardiomyocyte apoptosis was
      assessed by TUNEL staining. Myocardial TNFalpha, Caspase-3, STAT3, Akt, and GSK
      3beta were determined by Western blotting. RESULTS: Prolongation of ischemia but
      not reperfusion from 30 min to 45 min significantly increased infarct size in D
      compared to C rats (P < 0.05), accompanied with significantly increased plasma CK
      MB (P < 0.05). Prolongation of the duration of either ischemia or reperfusion
      significantly increased plasma LDH release and myocardial 15-F(2t)-Isoprostane
      and reduced plasma SOD activity, with concomitant reduction of myocardial NO and
      increase of nitrotyrosine formation in D relative to C (P < 0.05). Prolongation
      of ischemia and reperfusion significantly reduced left ventricular ejection
      fraction and increased the peak rate of pressure, accompanied with increased end
      systolic pressure in D relative to C rats (P < 0.05) but reduced phosphorylations
      of myocardial STAT3 at site Ser727 and Akt at site Ser473 as well as GSK-3beta at
      Ser 9 (P < 0.05). CONCLUSIONS: Diabetic hearts, even at early stage of the
      disease are more sensitive to IRI, and this increased severity of post-ischemic
      myocardial injury depends more on the duration of ischemia than that of
      reperfusion.

PMID- 24041265
TI  - One-pot synthesis of urchin-like FePd-Fe3O4 and their conversion into exchange
      coupled L1(0)-FePd-Fe nanocomposite magnets.
AB  - We report a one-pot synthesis of urchin-like FePd-Fe3O4 nanocomposites, spherical
      clusters of FePd nanoparticles (NPs) with spikes of Fe3O4 nanorods (NRs), via
      controlled thermal decomposition of Fe(CO)5 and reduction of Pd(acac)2. The FePd
      NPs with sizes between 6 and 9 nm self-aggregate into 60 nm superparticles (SPs),
      and Fe3O4 NRs grow on the surface of these SPs. Reductive annealing at 500 
      degrees C converts the FePd-Fe3O4 into exchange-coupled nanocomposites L1(0)-FePd
      Fe with their Hc tunable from 0.8 to 2.6 kOe and Ms controlled from 90 to 190
      emu/g. The work provides a general approach to L1(0)-FePd-Fe nanocomposite
      magnets for understanding exchange coupling at the nanoscale. The concept may be
      extended to other magnetic nanocomposite systems and may help to build
      superstrong magnets for magnetic applications.

PMID- 24041266
TI  - A photo-driven polyoxometalate complex shuttle and its homogeneous catalysis and
      heterogeneous separation.
AB  - A "smart" core-shell complex is designed to combine a catalytic reaction and
      automatic separation through remote light control. Here, we present the induced
      amphiphilic behavior of a surfactant-encapsulated polyoxometalate complex with
      photoresponsive azobenzene units on the periphery. The reversible phase transfer
      of the complex shuttle between two incompatible phase termini, driven by a
      photoisomerization-induced polarity change, further facilitates the separation
      and recycle of the catalyst. 

PMID- 24041267
TI  - Influence of crystallite size on cation conductivity in faujasitic zeolites.
AB  - The influence of particle size on the ionic conductivity of ceramic materials is
      an active area of research, and novel effects are observed as particles approach
      the nanoscale in size. Zeolites are crystalline aluminosilicates with ion
      exchangeable cations that are responsible for ionic conductivity at high
      temperatures. In this paper, we present systematic results for the first time of
      ionic conductivity in alkali metal ion-exchanged faujasitic zeolites with
      morphologies ranging from a zeolite membrane, micrometer-sized, submicrometer,
      and nanoparticles of zeolite. Using impedance spectroscopy in the range of 10 MHz
      to 0.1 Hz, we have obtained the activation energy (E(act)) of cation motion with
      these various morphologies in the temperature range of 525-625  degrees C.
      Overall, the E(act) decreases with Si/Al ratio. Surface modification of the
      zeolite particles was carried out with a silylating agent, which upon high
      temperature calcination should lead to the formation of a monolayer Si-O-Si film
      on the particle surface. This surface modification had minimal influence on the
      E(act) of micrometer-sized zeolites. However, E(act) increased rapidly as the
      zeolite particle approached the nanoscale. These observations led us to propose
      that, for the high-temperature, low-frequency (10(4)-10(5) Hz), long-range ionic
      conduction in zeolites, cation hopping across grain boundaries is relevant to ion
      transport, especially as the size of the crystallite approaches the nanoscale.
      Intergrain boundaries are more defective in the nanosized zeolite and contribute
      to the higher E(act).

PMID- 24041268
TI  - Research consultation clinic: impetus towards facilitating primary care research.
AB  - BACKGROUND: In Singapore, SingHealth Polyclinics (SHP) is an accredited Family
      Medicine (FM) training centre which managed 1.8 million primary care patient
      visits in 2012. To promote research in the institution, research consultation
      clinics (RCC) are being introduced in 2010 to enable free face-to-face
      consultation between experienced and novice researchers on specific research
      topics. Each RCC session allows about an hour or more for the SHP staff, medical
      undergraduates and general practitioners to seek advice and clarification on key
      research areas, ranging from research question refinement, study design and
      execution, data analysis, result presentation to publication. The consultants
      comprise of two FM researchers with postgraduate research qualification. AIM:
      This article aims to review the implementation of RCC from 2010 to 2012 and its
      impact on research activities and outcome indicators in the same period of time.
      METHODS: The study comprised of two segments. Part I was a three-year
      retrospective review of the RCC administrative record. The total number of RCC
      sessions, hours utilised, participants' profiles, the number of research studies
      initiated by them and their research presentations at local and overseas
      scientific meetings/conferences were computed. Part 2 was an anonymous web-based
      questionnaire survey fielded to RCC participants to collect their feedback on the
      RCC service and their self-reported initiation and completion of research study
      after the RCC consultation. RESULTS: The RCC sessions increased from 17 to 40
      sessions, resulting in increment of 2 to 14 research presentations and from 2 to
      6 initiations of new research studies per annum from 2010-2012. The response rate
      to the questionnaire survey was 70.3%, with the majority of multi-disciplinary
      respondents rated the RCC service to be accessible, adequate and were satisfied
      with its quality. Study design, data management and study execution were ranked
      as important areas of research for consultation. 79% of them had started a
      research project and 36% had completed their studies. CONCLUSIONS: The RCC is a
      feasible model to catalyse multi-disciplinary research in primary care
      institutions. Further study is needed to evaluate its relevance when research
      advances and novice researchers become experienced investigators to take on more
      complex projects.

PMID- 24041269
TI  - Stem cell transplantation for chronic myeloid leukemia (CML): current indications
      and perspectives.
AB  - The introduction of tyrosine kinase inhibitors (TKIs) has reduced the indications
      for allogeneic stem cell transplants (SCT) in patients with chronic myeloid
      leukemia (CML) from 1500/year in 2000 to approximately 500/year in 2010. The
      recently updated indications by the European Leukemia Network include advanced
      phase CML and nonresponders to second-line TKIs. Changes in transplant programs,
      over the past decade, have resulted in a significant reduction in transplant
      related mortality and this has expanded the transplant option to older patients,
      who may be eligible for SCT. Transplantation for blastic phase CML remains a
      challenge due to the high rate of post-transplant relapses. Thus, in view of this
      issue, several studies of TKIs after allogeneic SCT have been undertaken with
      encouraging results. In conclusion, allogeneic SCT remains a therapeutic option
      for selected patients with CML and is currently being integrated with the use of
      TKIs both before and after transplantation. 

PMID- 24041270
TI  - Predictors of psychiatric hospitalization during 6 months of maintenance
      treatment with olanzapine long-acting injection: post hoc analysis of a
      randomized, double-blind study.
AB  - BACKGROUND: Hospitalization is a costly and distressing event associated with
      relapse during schizophrenia treatment. No information is available on the
      predictors of psychiatric hospitalization during maintenance treatment with
      olanzapine long-acting injection (olanzapine-LAI) or how the risk of
      hospitalization differs between olanzapine-LAI and oral olanzapine. This study
      aimed to identify the predictors of psychiatric hospitalization during
      maintenance treatment with olanzapine-LAI and assessed four parameters:
      hospitalization prevalence, incidence rate, duration, and the time to first
      hospitalization. Olanzapine-LAI was also compared with a sub-therapeutic dose of
      olanzapine-LAI and with oral olanzapine. METHODS: This was a post hoc exploratory
      analysis of data from a randomized, double-blind study comparing the safety and
      efficacy of olanzapine-LAI (pooled active depot groups: 405 mg/4 weeks, 300 mg/2
      weeks, and 150 mg/2 weeks) with oral olanzapine and sub-therapeutic olanzapine
      LAI (45 mg/4 weeks) during 6 months' maintenance treatment of clinically stable
      schizophrenia outpatients (n=1064). The four psychiatric hospitalization
      parameters were analyzed for each treatment group. Within the olanzapine-LAI
      group, patients with and without hospitalization were compared on baseline
      characteristics. Logistic regression and Cox's proportional hazards models were
      used to identify the best predictors of hospitalization. Comparisons between the
      treatment groups employed descriptive statistics, the Kaplan-Meier estimator and
      Cox's proportional hazards models. RESULTS: Psychiatric hospitalization was best
      predicted by suicide threats in the 12 months before baseline and by prior
      hospitalization. Compared with sub-therapeutic olanzapine-LAI, olanzapine-LAI was
      associated with a significantly lower hospitalization rate (5.2% versus 11.1%, p
      < 0.01), a lower mean number of hospitalizations (0.1 versus 0.2, p = 0.01), a
      shorter mean duration of hospitalization (1.5 days versus 2.9 days, p < 0.01),
      and a similar median time to first hospitalization (35 versus 60 days, p = 0.48).
      Olanzapine-LAI did not differ significantly from oral olanzapine on the studied
      hospitalization parameters. CONCLUSIONS: In clinically stable schizophrenia
      outpatients receiving olanzapine-LAI maintenance treatment, psychiatric
      hospitalization was best predicted by a history of suicide threats and prior
      psychiatric hospitalization. Olanzapine-LAI was associated with a significantly
      lower incidence of psychiatric hospitalization and shorter duration of
      hospitalization compared with sub-therapeutic olanzapine-LAI. Olanzapine-LAI did
      not differ significantly from oral olanzapine on hospitalization parameters.
      TRIAL REGISTRATION: ClinicalTrials.gov: NCT00088491.

PMID- 24041271
TI  - Impact of osmotic stress and ethanol inhibition in yeast cells on process
      oscillation associated with continuous very-high-gravity ethanol fermentation.
AB  - BACKGROUND: VHG fermentation is a promising process engineering strategy aiming
      at improving ethanol titer, and thus saving energy consumption for ethanol
      distillation and distillage treatment. However, sustained process oscillation was
      observed during continuous VHG ethanol fermentation, which significantly affected
      ethanol fermentation performance of the system. RESULTS: Sustained process
      oscillation was investigated in continuous VHG ethanol fermentation, and stresses
      exerted on yeast cells by osmotic pressure from unfermented sugars and ethanol
      inhibition developed within the fermentation system were postulated to be major
      factors triggering this phenomenon. In this article, steady state was established
      for continuous ethanol fermentation with LG medium containing 120 g/L glucose,
      and then 160 g/L non-fermentable xylose was supplemented into the LG medium to
      simulate the osmotic stress on yeast cells under the VHG fermentation condition,
      but the fermentation process was still at steady state, indicating that the
      impact of osmotic stress on yeast cells was not the main reason for the process
      oscillation. However, when 30 g/L ethanol was supplemented into the LG medium to
      simulate the ethanol inhibition in yeast cells under the VHG fermentation
      condition, process oscillation was triggered, which was augmented with extended
      oscillation period and exaggerated oscillation amplitude as ethanol
      supplementation was increased to 50 g/L, but the process oscillation was
      gradually attenuated when the ethanol supplementations were stopped, and the
      steady state was restored. Furthermore, gas stripping was incorporated into the
      continuous VHG fermentation system to in situ remove ethanol produced by
      Saccharomyces cerevisiae, and the process oscillation was also attenuated, but
      restored after the gas stripping was interrupted. CONCLUSIONS: Experimental
      results indicated that ethanol inhibition rather than osmotic stress on yeast
      cells is one of the main factors triggering the process oscillation under the VHG
      fermentation condition, and in the meantime gas stripping was validated to be an
      effective strategy for attenuating the process oscillation.

PMID- 24041272
TI  - Perception and reality - Portuguese adults' awareness of active lifestyle.
AB  - This study aims to assess awareness of physical activity levels among adults and
      to investigate the variables associated with different types of awareness. The
      participants were 1042 men and 1316 women aged 31-60 years old (43.3 +/- 6.1).
      Data were collected on physical activity behaviour, physical activity awareness,
      perceptions and psychological factors. Awareness was assessed by comparing self
      rated physical activity with achieving physical activity guidelines. Chi-square
      and logistic regression analyses were applied to the results. About 32.4% were
      considered active. Moreover, 61% accurately reported their physical activity
      (38.3% realistic inactive and 22.7% realistic active), 29.2% overestimated their
      physical activity (overestimators) and 9.7% incorrectly described themselves as
      inactive (underestimators). Perception of an excellent health status (odds ratio,
      OR = 4.07, 95% confidence interval, CI: 2.07-8.00, p < 0.001) was the strongest
      positive association with being realistic active, followed by having a high socio
      economic status (SES) (OR = 1.53, 95% CI: 1.10-2.12, p < 0.05). Overestimator
      participants were more likely to have an excellent perception of health (OR =
      2.58, 95% CI: 1.47-4.52, p < 0.01) and had a good experience in physical
      education (OR = 1.46, 95% CI:1.03-2.08, p < 0.05). Almost half of these
      participants erroneously perceived themselves as physically active. Gender, body
      mass index (BMI) and the quality of physical education at school were associated
      with those who misperceived their physical activity.

PMID- 24041273
TI  - Topochemical reduction of the Ruddlesden-Popper phases Sr2Fe(0.5)Ru(0.5)O4 and
      Sr3(Fe(0.5)Ru(0.5))2O7.
AB  - Reaction of the Ruddlesden-Popper phases Sr2Fe(0.5)Ru(0.5)O4 and
      Sr3(Fe(0.5)Ru(0.5))2O7 with CaH2 results in the topochemical deintercalation of
      oxide ions from these materials and the formation of samples with average
      compositions of Sr2Fe(0.5)Ru(0.5)O(3.35) and Sr3(Fe(0.5)Ru(0.5))2O(5.68),
      respectively. Diffraction data reveal that both the n = 1 and n = 2 samples
      consist of two-phase mixtures of reduced phases with subtly different oxygen
      contents. The separation of samples into two phases upon reduction is discussed
      on the basis of a short-range inhomogeneous distribution of iron and ruthenium in
      the starting materials. X-ray absorption data and Mossbauer spectra reveal the
      reduced samples contain an Fe(3+) and Ru(2+/3+) oxidation state combination,
      which is unexpected considering the Fe(3+)/Fe(2+) and Ru(3+)/Ru(2+) redox
      potentials, suggesting that the local coordination geometry of the transition
      metal sites helps to stabilize the Ru(2+) centers. Fitted Mossbauer spectra of
      both the n = 1 and n = 2 samples are consistent with the presence of Fe(3+)
      cations in square planar coordination sites. Magnetization data of both materials
      are consistent with spin glass-like behavior.

PMID- 24041274
TI  - TBscore II: refining and validating a simple clinical score for treatment
      monitoring of patients with pulmonary tuberculosis.
AB  - BACKGROUND: The TBscore, based on simple signs and symptoms, was introduced to
      predict unsuccessful outcome in tuberculosis patients on treatment. A recent
      inter-observer variation study showed profound variation in some variables.
      Further, some variables depend on a physician assessing them, making the score
      less applicable. The aim of the present study was to simplify the TBscore.
      METHODS: Inter-observer variation assessment and exploratory factor analysis were
      combined to develop a simplified score, the TBscore II. To validate TBscore II we
      assessed the association between start score and failure (i.e. death or treatment
      failure), responsiveness using Cohen's effect size, and the relationship between
      severity class at treatment start and a decrease < 25% in score from the start
      until the end of the second treatment month and subsequent mortality. RESULTS: We
      analyzed data from 1070 Guinean (2003-2012) and 432 Ethiopian (2007-2012)
      pulmonary tuberculosis patients. For the refined score, items with less than
      substantial agreement (kappa <= 0.6) and/or not associated with the underlying
      constructs were excluded. Items kept were: cough, dyspnea, chest pain, anemia,
      body mass index (BMI) < 18 kg/m(2), BMI < 16 kg/m(2), mid upper arm circumference
      (MUAC) < 220 mm, and MUAC < 200 mm. The effect sizes for the change between the
      start of treatment and the 2-month follow-up were 0.51 in Guinea-Bissau and 0.68
      in Ethiopia, and for the change between the start of treatment and the end of
      treatment were 0.68 in Guinea-Bissau and 0.74 in Ethiopia. Severity class
      placement at treatment start predicted failure (p < 0.001 Guinea-Bissau, p =
      0.208 Ethiopia). Inability to decrease at least 25% in score was associated with
      a higher failure rate during the remaining 4 months of treatment (p = 0.063
      Guinea-Bissau, p = 0.008 Ethiopia). CONCLUSION: The TBscore II could be a useful
      monitoring tool, aiding triage at the beginning of treatment and during
      treatment.

PMID- 24041275
TI  - Vesalius and the emergence of veridical representation in Renaissance anatomy.
AB  - The Renaissance marks the introduction of veridical representation of anatomical
      structure into printed books. For centuries, anatomy that had relied solely on
      textual description and the authority of the written word was transformed. An
      existing graphic tradition only visualized function within a humoral theory,
      schematically "naming the parts" or mapping the "uses of the parts" for mnemonic
      purposes. In the sixteenth century, anatomists and artist began to apply their
      knowledge and skills to present the "fabric" of the dissected human body with
      increasing detail and accuracy, exemplified by the naturalistic illustrations of
      the brain in Vesalius' De humani corporis fabrica (Basel, 1543). How did this
      transformation occur? Among the causal factors, the importance the humanist
      textual scholarship will be shown not only in the recovery of the anatomical
      writings of Galen (129-ca. 216), in particular, but also in providing a model in
      establishing anatomical "truth" by a method of "comparison." It will be argued
      that Vesalius' comparative approach in dissection, using both human and animal
      preparations against Galen's textual description, paved the way for cumulative
      observations of greater detail, which in turn required the representational
      skills of artists. An analysis of Vesalius' views between 1538 and 1543 shows a
      shift in the use of illustrations from serving as a visual record to compensate
      for limited access to cadavers in teaching, to becoming an indispensable tool to
      accurately convey detailed anatomical structure through the medium of printing.
      With the Fabrica, morphology became divorced from humoral function and enduring
      paradigms established that dominated until the nineteenth century. 

PMID- 24041276
TI  - Medieval and Renaissance anatomists: the printing and unauthorized copying of
      illustrations, and the dissemination of ideas.
AB  - The vanguard that began to question Galenic anatomical dogma originated in
      northern Italy in the latter half of the thirteenth century, and not
      coincidentally this was where human dissection was introduced, which in turn
      eventually fostered the origins of realistic anatomical illustration in the late
      fifteenth century. With the advent of the printing press and moveable type at
      this time, printed books began to supersede hand-copied medieval manuscripts, and
      labor-intensive techniques were soon developed to integrate text and
      illustrations on the printed page. The same technology was used to pirate the
      illustrations of prior authors with varying fidelity. Specific medieval and
      Renaissance anatomical illustrations can often be traced from their inceptions
      through different stages of development to the final printed images, and then
      through subsequent pirated versions in various abridgements or other compendia.
      The most important milestone in the development of anatomy and anatomical
      illustration was the publication in 1543 by Andreas Vesalii of De humani corporis
      fabrica (On the Fabric of the Human Body), commonly referred to simply as the
      Fabrica. With this work, Vesalii succeeded in coordinating a publication
      production team (author, artists, block cutters, publisher, and typesetters) to
      achieve an unprecedented integration of scientific discourse, medical
      illustration, and typography. However, despite Vesalii's valiant efforts to
      prevent unauthorized duplication, the illustrations from the Fabrica were
      extensively plagiarized. Although Vesalii found such piracy frustrating and
      annoying, the long-term effect was to make Vesalii's ideas known to a wider
      readership and to help solidify his own revolutionary contributions to anatomy. 

PMID- 24041277
TI  - Anna Morandi's wax self-portrait with brain.
AB  - In her self-portrait in wax, eighteenth-century Bolognese anatomist and
      anatomical modeler Anna Morandi Manzolini (1714-1774) represented herself in
      sumptuous aristocratic dress while dissecting a human brain. This essay explores
      the scientific and symbolic meaning of the vivid self-portrayal in terms of Anna
      Morandi's lifework at the intersection of art and anatomical science and within
      the remarkable cultural context of Enlightenment Bologna that fostered her rise
      to international acclaim. 

PMID- 24041278
TI  - David Ferrier: brain drawings and brain maps.
AB  - This chapter has two emphases, one is about the men who influenced the visual
      representations that David Ferrier (1843-1928) used to illustrate his work on
      localization of brain functions during the years 1873-1875, namely, Alexander
      Ecker, John C. Galton, and Ernest Waterlow, and the other is about the nature of
      medical representations and of Ferrier's illustrations in particular. Medical
      illustrations are characterized either as pictures, line drawings, or brain maps.
      Ferrier's illustrations will be shown to be increasingly sophisticated brain maps
      that contrast with early nineteenth-century standards of medical illustrations,
      as exemplified by John Bell (1763-1829). 

PMID- 24041279
TI  - Neura, nerves, nerve fibers, neurofibrils, microtubules: multidimensional routes
      of pain, pleasure, and voluntary action in images across the ages.
AB  - Available records indicate that the human body has always been conceived, in
      different periods and cultures, as spanned by multiple channels for internal
      communication and coherent functioning as a unit-"meridians" in treatises of
      Chinese medicine, metu in Egyptian papyri, srotas in Ayurvedic Indian texts, and
      neura in the Western scientific heritage from ancient Greece. Unfortunately, the
      earliest extant figurative depictions of such pathways of general control,
      complementary to the blood vessels, are late medieval copies of old crude
      sketches that attempted to show the main anatomico-physiological systems. The
      scarcity of adequate illustrations was more than compensated in the Renaissance,
      when the efforts of both artists and anatomists for the first time produced
      basically correct renditions of the human nervous system and many other bodily
      structures. As attention was next focused on microscopic structure as a requisite
      to understand physiological mechanisms, during the Enlightenment the nerves were
      revealed to consist of numerous thin tubes or fibers aligned in parallel.
      Improved microscopy techniques in the nineteenth century led to discovering and
      delineating still finer fibrils coursing along the cores of the nerve fibers
      themselves. Electron microscopy, developed throughout the twentieth century,
      recognized some of these fibrils within nerve fibers as being also tubular. All
      the progressive stages in understanding nerve construction, at increasingly more
      detailed scales, have been accompanied by technological advances and by debate
      about the structure and function relationship. And every step has been a source
      of amazing imagery. 

PMID- 24041280
TI  - John Bell (1763-1820): brother artist and anatomist.
AB  - John Bell, brother-surgeon of Charles Bell, was, like Charles, an outstanding
      surgeon and a good artist. John was one of the few who illustrated his work with
      their own drawings in the days before audiovisual aids were available and without
      the benefit of reliable drawing aids, photography and computer-aided design.
      Charles, on the other hand, was the better artist and illustrated much of the
      normal anatomy of the nervous system. Each brother undertook extensive surgery of
      men who had been wounded in war; John Bell left us his engravings from the
      textbooks, more numerous perhaps than Charles, but Charles left us a series of
      oil paintings and watercolours in addition to the illustrations in his textbooks.

PMID- 24041281
TI  - Jean-Martin Charcot and art: relationship of the "founder of neurology" with
      various aspects of art.
AB  - Jean-Martin Charcot (1825-1893), the "father of neurology" in France and much
      beyond, was also the man who established academic psychiatry in Paris,
      differentiating it from clinical alienism. In his teaching, he used artistic
      representations from previous centuries to illustrate the historical developments
      of hysteria, mainly with the help of his pupil Paul Richer. Charcot liked to draw
      portraits (in particular, sketches of colleagues during boring faculty meetings
      and students' examinations), caricatures of himself and others, church
      sculptures, landscapes, soldiers, etc. He also used this skill in his clinical
      and scientific work; he drew histological or anatomic specimens, as well as
      patients' features and demeanor. His most daring artistic experiments were
      drawing under the influence of hashish. Charcot's tastes in art were
      conservative; he displayed no affinity for the avant-gardes of his time,
      including impressionism, or for contemporary musicians, such as Cesar Franck or
      Hector Berlioz. Leon Daudet, son of Charcot's former friend and famous writer
      Alphonse Daudet, described Charcot's home as a pseudo-gothic kitsch accumulation
      of heteroclite pieces of furniture and materials. However, as Henry Meige wrote a
      few years after his mentor's death, Charcot the artist remains "inseparable from
      Charcot the physician." 

PMID- 24041282
TI  - Cajal and the discovery of a new artistic world: the neuronal forest.
AB  - The introduction of the staining method of Camillo Golgi in 1873 represented a
      giant step for neuroscience. Prior to this development, the visualization of
      neurons with the available histological techniques had been incomplete; it was
      only feasible to observe the cell body and the proximal portions of the dendrites
      and axon. However, with the Golgi method it was possible to observe neurons and
      glia with all their parts (cell body, dendrites, and axon in the case of neurons;
      cell body and processes in the case of glia). Due to the advantages of this
      method, all of a sudden it was possible to begin studying one of the great
      mysteries and critical issues of the organization of the nervous system-the
      tracing of the connections between neurons. Nevertheless, this method was not
      fully exploited until Santiago Ramon y Cajal arrived on the scene in 1888. It
      should be noted that, in Cajal's day, drawing was the most common method of
      describing microscopic images in the absence of the highly developed
      microphotography and other imaging techniques commonly available in today's
      laboratories. As a consequence, most scientific figures presented by the early
      neuroanatomists were their own drawings, providing an outlet for these scientists
      to express and develop their artistic talent. In the hands of Cajal, the Golgi
      method represented not only the principal tool that was to change the course of
      the history of neuroscience but also the discovery of a new artistic world, the
      neuronal forest. 

PMID- 24041283
TI  - The lead-poisoned genius: saturnism in famous artists across five centuries.
AB  - Lead poisoning (saturnism) has been present throughout the history of mankind. In
      addition to possible ingestion from contaminated food, one of the most important
      ways in which poisoning caused morbid processes was by occupational exposure.
      This exposition was pandemic in the Roman Empire, and it has been claimed that it
      contributed to its fall, but it also caused numerous epidemics in Western
      countries until the nineteenth century. In the case of artists, and since the
      Renaissance period, this toxicity has been called painter's colic or painter's
      madness. The latter term is partly due to the mental disorders displayed by some
      of the great masters, including Michelangelo and Caravaggio, although it was long
      recognized that even house and industrial painters were prone to the disorder.
      This chapter examines the historical evidence of recognition of such toxicity and
      discusses the controversies raised by the possibility of professional lead
      poisoning in great artists. In addition to those mentioned above, many other
      artists across several centuries will be discussed, some being Rubens, Goya,
      Fortuny, Van Gogh, Renoir, Dufy, Klee, Frida Kahlo, and Portinari. This chapter
      also briefly mentions the possibility of lead poisoning in two famous composers:
      Beethoven and Handel. Whether suffering from lead poisoning or not, about which
      we cannot always be sure, we should still highlight and admire such geniuses
      fighting their disorders to bequeath us their immortals works. 

PMID- 24041284
TI  - Frida Kahlo's neurological deficits and her art.
AB  - World-famous Mexican painter Frida Kahlo is an impressive example of a
      professional artist whose artistic subject matter was extremely influenced by her
      chronic, severe illness. Many of her best-known works depict her physical and
      mental suffering. She was one of those very uncommon artists who dared to show
      their nude, sick body. This chapter describes and explains the biographical
      events and works of Frida Kahlo that are closely related to neurology: congenital
      anomaly (spina bifida), poliomyelitis, spine injury, and neuropathic pain. 

PMID- 24041285
TI  - Neurological diseases in famous painters.
AB  - Visual art production involves multiple processes including basic motor skills,
      such as coordination of movements, visual-spatial processing, emotional output,
      sociocultural context, and creativity. Thus, the relationship between artistic
      output and brain diseases is particularly complex, and brain disorders may lead
      to impairment of artistic production in multiple domains. Neurological conditions
      may also occasionally modify artistic style and lead to surprisingly innovative
      features in people with an initial loss of creativity. This chapter focuses on
      anecdotal reports of various neurological disorders and their potential
      consequences on works produced by famous or well-established artists, including
      Carl Frederik Reutersward, Giorgio de Chirico, Krystyna Habura, Leo Schnug,
      Ignatius Brennan, and many others. 

PMID- 24041286
TI  - Preface.

PMID- 24041287
TI  - Controlling release from pH-responsive microcapsules.
AB  - We report a microfluidic approach to produce monodisperse pH-responsive
      microcapsules with precisely controlled release behavior. The solid microcapsule
      shells are composed of a biocompatible pH-responsive polymer and robustly
      encapsulate an active material; however, when exposed to a trigger pH, the shells
      degrade and ultimately release the microcapsule contents. We control the trigger
      pH by using polymers that dissolve at different pH values. We independently
      control the time at which the microcapsule contents are released by carefully
      controlling the shell thickness. Moreover, we independently control the rate at
      which the encapsulated contents are released by making hybrid shells composed of
      a mixture of a pH-responsive polymer and varying proportions of another, solid,
      pH-unresponsive polymer. This enables us to achieve monodisperse microcapsules
      that robustly encapsulate an active material, only releasing it when exposed to a
      desired pH, after a prescribed time delay, and at a prescribed rate. 

PMID- 24041288
TI  - Active and passive fatigue in simulated driving: discriminating styles of
      workload regulation and their safety impacts.
AB  - Despite the known dangers of driver fatigue, it is a difficult construct to study
      empirically. Different forms of task-induced fatigue may differ in their effects
      on driver performance and safety. Desmond and Hancock (2001) defined active and
      passive fatigue states that reflect different styles of workload regulation. In 2
      driving simulator studies we investigated the multidimensional subjective states
      and safety outcomes associated with active and passive fatigue. Wind gusts were
      used to induce active fatigue, and full vehicle automation to induce passive
      fatigue. Drive duration was independently manipulated to track the development of
      fatigue states over time. Participants were undergraduate students. Study 1 (N =
      108) focused on subjective response and associated cognitive stress processes,
      while Study 2 (N = 168) tested fatigue effects on vehicle control and alertness.
      In both studies the 2 fatigue manipulations produced different patterns of
      subjective response reflecting different styles of workload regulation,
      appraisal, and coping. Active fatigue was associated with distress, overload, and
      heightened coping efforts, whereas passive fatigue corresponded to large
      magnitude declines in task engagement, cognitive underload, and reduced challenge
      appraisal. Study 2 showed that only passive fatigue reduced alertness,
      operationalized as speed of braking and steering responses to an emergency event.
      Passive fatigue also increased crash probability, but did not affect a measure of
      vehicle control. Findings support theories that see fatigue as an outcome of
      strategies for managing workload. The distinction between active and passive
      fatigue is important for assessment of fatigue and for evaluating automated
      driving systems which may induce dangerous levels of passive fatigue.

PMID- 24041290
TI  - Do we really want to grow the field of palliative medicine?

PMID- 24041291
TI  - Team interactions in specialized palliative care teams: a qualitative study.
AB  - BACKGROUND: Teamwork is a standard of care in palliative care and that is
      emphasized by leading organizations. When interdisciplinary teams communicate
      their varied assessments, outcomes may be more than additive due to the synthesis
      of information. Interprofessionality does not guarantee multidimensionality in
      health care interventions, however, and that interprofessional teams promote
      collaboration may be questioned. AIM: The aim was to explore team interaction
      among team members in specialized palliative care teams. DESIGN: Semistructured
      interviews were conducted with health professionals working in specialized
      palliative home care teams. The interviews were analyzed by content analysis.
      SETTING/PARTICIPANTS: Participants were recruited from specialized palliative
      care units in Sweden. The 15 interviewees included 4 men and 11 women. Physcians,
      nurses, paramedical staff, and social workers were included. RESULTS:
      Organizational issues like resources and leadership have a great impact on
      delivery of care. Competence was mirrored in education, collaboration, approach,
      and support within the team; while communication was described as key to being a
      team, resolving conflict, and executing palliative care. CONCLUSION:
      Communication and communication patterns within the team create the feeling of
      being a team. Team climate and team performance are significantly impacted by
      knowledge and trust of competence in colleagues, with other professions, and by
      the available leadership. Proportions of different health professionals in the
      team have an impact on the focus and delivery of care. Interprofessional
      education giving clarity on one's own professional role and knowledge of other
      professions would most likely benefit patients and family caregivers.

PMID- 24041292
TI  - Diagnosis of depression in patients receiving specialist community palliative
      care: does using a single screening question identify depression otherwise
      diagnosed by clinical interview?
AB  - BACKGROUND: Depression affects a quarter of palliative patients and is associated
      with reduced quality of life. Screening for psychological problems at key points
      in the patients' pathway is recommended but there is no consensus as to how to do
      this. AIMS: The study's aim was to assess the efficacy of a screening question
      for depression against a semistructured interview in patients referred to a
      specialist community palliative care team. METHODS: Fifty community palliative
      care patients were assessed using a single question: "Have you felt depressed,
      most of the day, nearly every day for two or more weeks?" Results were compared
      with assessment using the validated Mini International Neuropsychiatric Interview
      (MINI). RESULTS: Sensitivity of the single question was 0.8 and specificity was
      0.85. The positive predictive value was 0.57 and the negative predictive value
      was 0.94. CONCLUSION: The screening question was shown to have acceptable
      sensitivity and specificity in a small sample of community palliative care
      patients. It is likely to be most useful to accurately identify those who are not
      depressed and identify those patients who need a more in-depth assessment of
      their mood.

PMID- 24041294
TI  - Behavioral evaluation of regenerated rat sciatic nerve by a nanofibrous PHBV
      conduit filled with Schwann cells as artificial nerve graft.
AB  - The aim of this study is to develop a nanofibrous polymeric nerve conduit with
      Schwann cells (SCs) and to evaluate its efficiency on the promotion of functional
      and locomotive activities in rats. The conduits were implanted into a 30-mm gap
      in the sciatic nerves of the rats. Four months after surgery, the rats were
      monitored and evaluated by behavioral analyses such as toe out angle, toe
      spreading analysis, walking track analysis, extensor postural thrust, open-field
      analysis, swimming test and nociceptive function, four months post surgery. Four
      months post-operatively, the results from behavioral analyses demonstrated that
      in the grafted groups especially in the grafted group with SCs, the rat sciatic
      nerve trunk had been reconstructed with functional recovery such as walking,
      swimming and recovery of nociceptive function. This study proves the feasibility
      of artificial conduit with SCs for nerve regeneration by bridging a longer defect
      in the rat model.

PMID- 24041295
TI  - Photoinduced charge transfer in solvated anthraquinones is facilitated by low
      frequency ring deformations.
AB  - Efficiency of photoinduced charge transfer (CT) reactions in supramolecular
      assemblies is often compromised due to the rigid parametrization of acceptable
      donor-acceptor (D-A) distances and orientations. Using a combined approach of
      time-resolved optical measurements and electronic structure studies guided by
      molecular dynamics (MD) simulations, we demonstrate that dynamic control on CT
      rate exists for quenching of hydroxy-anthraquinones in donor aniline-like
      solvents. We find that anthraquinone ring deformation modes control the kinetics
      of CT within ~300-700 fs by modulating the D-A electronic couplings. Our work
      demonstrates that low-frequency motions have to be critically understood for all
      such D-A pairs, and generates a rational methodology for utilization of hydroxy
      anthraquinone acceptors in numerous photoactive architectures. 

PMID- 24041296
TI  - A study on relapse/re-infection rate of Plasmodium vivax malaria and
      identification of the predominant genotypes of P. vivax in two endemic districts
      of Nepal.
AB  - BACKGROUND: Malaria is a major public health problem in Nepal inflicted primarily
      by the parasite Plasmodium vivax, - the only species responsible for relapse
      cases in Nepal. Knowledge on its relapse rate is important for successful malaria
      control, but is lacking in Nepal. The information on circulating predominant
      genotypes of P. vivax is equally relevant for high endemic districts of Nepal to
      understand the transmission dynamics of the parasite and to uncover the coverage
      and efficacy of potential vaccine beforehand. METHODS: A prospective
      observational study with a six months follow-up period was conducted from August
      2010 to May 2011 in four health centres of Kailali and Kanchanpur districts of
      Nepal to access the relapse/re-infection rate of P. vivax. The prevalence and
      heterogeneity of its genotypes were identified by PCR-RFLP assay targeting
      central repeat region of circumsporozoite protein (Pvcsp). RESULTS: In total, 137
      cases microscopically suspected to have P. vivax infection were enrolled in the
      study. Of these, 23 cases (17%) were detected for the relapse/ re-infection
      during a six-month period, with a high proportion being male cases of age group
      11-20 years. For genotyping, 100 whole blood samples were analysed, of which 95%
      of the parasite isolates were found to be of VK210 genotype. The minor genotype
      VK247 existed either in isolation or as mixed infection with VK210 in rest of the
      samples. CONCLUSIONS: The relapse/re-infection rate of 17% was determined for P.
      vivax in Kailali and Kanchanpur districts of Nepal. A heterogeneous Pvcsp
      genotypic distribution of P. vivax was detected with VK210 being a predominant
      type, suggesting a complex transmission dynamics of the parasite. Expanding such
      study in other endemic regions of Nepal would help provide a complete picture on
      relapse/re-infection rate and parasite genotypic variability that can help in
      effective control and management of malaria in Nepal.

PMID- 24041297
TI  - White-matter tract integrity in late-life depression: associations with severity
      and cognition.
AB  - BACKGROUND: Although significant changes in both gray and white matter have been
      noted in late-life depression (LLD), the pathophysiology of implicated white
      matter tracts has not been fully described. In this study we examined the
      integrity of specific white-matter tracts in LLD versus healthy controls (HC).
      METHOD: Participants aged ?60 years were recruited from the community. The sample
      included 23 clinically diagnosed individuals with LLD and 23 HC. White-matter
      integrity metrics [fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD) and radial diffusivity (RD)] were calculated in the bilateral
      cingulum and uncinate fasciculus. Depression severity was measured using the
      Center for Epidemiological Studies Depression Scale (CESD). Composite scores for
      learning and memory and executive function were created using standardized
      neuropsychological assessments. RESULTS: White-matter integrity was lower in LLD
      versus HC in the bilateral cingulum and right uncinate fasciculus (p?0.05). In
      the whole sample, depression severity correlated with integrity in the bilateral
      cingulum and right uncinate fasciculus (p ?0.05). In patients, depression
      severity correlated with the integrity of the left uncinate fasciculus (p =
      0.03); this tract also correlated with executive function (p = 0.02). Among HC,
      tract integrity did not correlate with depression scores; however, learning and
      memory correlated with integrity of the bilateral uncinate fasciculus and
      bilateral cingulum; executive function correlated with the right uncinate and
      left cingulum (p ?0.05). CONCLUSIONS: White-matter tract integrity was lower in
      LLD than in HC and was associated with depression severity across all
      participants. Tract integrity was associated with cognition in both groups but
      more robustly among HC.

PMID- 24041299
TI  - Immediate Implant Placement in a Patient With Osteoporosis Undergoing
      Bisphosphonate Therapy: 1-Year Preliminary Prospective Study.
AB  - The purposes of this preliminary study are to assess the risk of developing
      bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a patient with
      osteoporosis using zoledronic acid and to report the results of a 1-year
      prospective clinical study regarding 5 immediately inserted implants in the
      anterior mandible. For this comparative prospective study, 24 female patients,
      aged >=54 years, were chosen, all with partially edentulous mandibles. Group A
      consisted of 12 patients with osteoporosis taking zoledronic acid receiving a
      once-yearly intravenous infusion of zoledronic acid (5 mg). Control group B
      consisted of 12 other patients without osteoporosis and not taking drugs. In both
      groups, the remaining teeth were extracted before 120 implants, 3.7-mm wide and
      16-mm long, were immediately installed in the interforaminal region of the
      mandibles. The 1-year implant survival rate was 100%. No apparent necrotic bone
      was observed among patients receiving zoledronic acid (group A) after implant
      surgery. Immediate implant osseointegration can be successful in a patient with
      osteoporosis using bisphosphonates, suggesting the safety of implantology as a
      treatment modality. 

PMID- 24041298
TI  - Bench-to-bedside review: Challenges of diagnosis, care and prevention of central
      catheter-related bloodstream infections in children.
AB  - Central venous catheters (CVCs) are indispensable in modern pediatric medicine.
      CVCs provide secure vascular access, but are associated with a risk of severe
      complications, in particular bloodstream infection. We provide a review of the
      recent literature about the diagnostic and therapeutic challenges of catheter
      related bloodstream infection (CRBSI) in children and its prevention. Variations
      in blood sampling and limitations in blood culturing interfere with accurate and
      timely diagnosis of CRBSI. Although novel molecular testing methods appear
      promising in overcoming some of the present diagnostic limitations of
      conventional blood sampling in children, they still need to solidly prove their
      accuracy and reliability in clinical practice. Standardized practices of catheter
      insertion and care remain the cornerstone of CRBSI prevention although their
      implementation in daily practice may be difficult. Technology such as CVC
      impregnation or catheter locking with antimicrobial substances has been shown
      less effective than anticipated. Despite encouraging results in CRBSI prevention
      among adults, the goal of zero infection in children is still not in range. More
      high-quality research is needed in the field of prevention, accurate and reliable
      diagnostic measures and effective treatment of CRBSI in children. 

PMID- 24041300
TI  - Assessment of Truflex articulating stylet versus conventional rigid Portex stylet
      as an intubation guide with the D-blade of C-Mac videolaryngoscope during
      elective tracheal intubation: study protocol for a randomized controlled trial.
AB  - BACKGROUND: A variety of videolaryngoscopes with angulated blade have been
      recently introduced into clinical practice. They provide an indirect view of the
      glottic structures in normal and challenging clinical settings. Despite the very
      good visualization of the laryngeal structures by these devices, the insertion
      and advancement of the endotracheal tube may be prolonged and occasionally fail
      as it does not conform to the enhanced angulation of the blade. To overcome this
      handicap, it is recommended to use a pre-shaped, styleted tracheal tube during
      intubation. Unfortunately, these malleable rigid stylets permit only a fixed
      shape to the advancing endotracheal tube. This may necessitate withdrawal of
      endotracheal tube-stylet assembly for reshaping, before undertaking a new
      attempt. This may cause soft tissue injury and hemodynamic disturbance.This
      single-blinded randomized clinical trial aims to overcome these handicaps using a
      novel method of dynamically changing the shape of the advancing endotracheal tube
      by Truflex articulating stylet as per need during D-blade C-Mac
      videolaryngoscopy. METHODS: One hundred and fifty four patients between 18 and 60
      years of age belonging to either sex undergoing tracheal intubation under uniform
      general anesthetic technique will be randomly divided into Portex malleable
      stylet group and Truflex articulating stylet group. The primary efficacy variable
      of success/failure between the two groups will be analyzed using the chi square
      test. For comparison of intubation times and the Intubation Difficulty Score,
      ANOVA will be used. Primary efficacy endpoint results will be successful or
      failed tracheal intubation in the first attempt, total intubation time and the
      intubation difficulty score. Secondary efficacy endpoints will be overall user
      satisfaction graded from 1 to 10 (1 = very poor, 10 = excellent), Cormack and
      Lehane's grading, glotticoscopy time and ETT negotiation time and total number of
      intubation attempts. Result of safety endpoints will include dental and airway
      trauma, hemodynamic disturbances, arrhythmias or cardiac arrest. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN57679531; Date of registration
      12/02/2013.

PMID- 24041301
TI  - Intelligence as it relates to conscious and unconscious memory influences.
AB  - We examine the relationship between a measure of intelligence and estimates of
      conscious and unconscious memory influences derived using Jacoby's (Jacoby, L. L.
      [1991]. A process dissociation framework: Separating automatic from intentional
      uses of memory. Journal of Memory and Language, 30, 513-541.) process
      dissociation procedure. We find a positive relationship between intelligence and
      conscious memory, and no relationship between intelligence and unconscious
      influences once the impact of conscious influences are removed (Experiment 1). We
      also find that when participants cannot engage in conscious strategies, such as
      when there is insufficient time for learning, the relationships observed in
      Experiment 1 are eliminated (Experiments 2A and 2B). Our results support the
      notion that individual differences in intelligence reflect differences in
      conscious strategic processes (Karis, D., Fabiani, M., & Donchin, E. [1984].
      "P300" and memory: Individual differences in the von Restorff effect. Cognitive
      Psychology, 16, 177-216.) and not differences in mental speed (Eysenck, H. J.
      (1984). Intelligence versus behavior. The Behavioral and Brain Sciences, 7, 290
      291; Jensen, A. R. [1982]. Bias in mental testing. New York, NY: Free Press).

PMID- 24041302
TI  - Effects of homograph meaning frequency on semantic satiation.
AB  - This study examined the effects of homograph meaning frequency on semantic
      satiation within an ambiguity resolution paradigm. Participants received 3
      homograph conditions: the concordant (QUICK-FAST-SPEEDY), discordant (HUNGER-FAST
      SPEEDY) and neutral (CEILING-FAST-SPEEDY). On each trial, a prime (e.g., QUICK)
      was presented for various numbers of repetitions. Afterward, the prime was
      removed and participants made relatedness judgments about a homograph and target.
      On half of the trials, the prime was related to a high-frequency meaning of the
      homograph, and on the other half of the trials, the prime was related to a low
      frequency meaning. The concordant condition yielded evidence of semantic
      satiation across meaning frequency conditions (QUICK-FAST-SPEEDY), but the
      discordant condition only yielded evidence of semantic satiation when the prime
      activated a subordinate meaning of the homograph (HUNGER-FAST-SPEEDY).

PMID- 24041303
TI  - Comparing comprehension measured by multiple-choice and open-ended questions.
AB  - This study compared the nature of text comprehension as measured by multiple
      choice format and open-ended format questions. Participants read a short text
      while explaining preselected sentences. After reading the text, participants
      answered open-ended and multiple-choice versions of the same questions based on
      their memory of the text content. The results indicated that performance on open
      ended questions was correlated with the quality of self-explanations, but
      performance on multiple-choice questions was correlated with the level of prior
      knowledge related to the text. These results suggest that open-ended and multiple
      choice format questions measure different aspects of comprehension processes. The
      results are discussed in terms of dual process theories of text comprehension.

PMID- 24041305
TI  - Sorption and redox reactions of As(III) and As(V) within secondary mineral
      coatings on aquifer sediment grains.
AB  - Important reactive phenomena that affect the transport and fate of many elements
      occur at the mineral-water interface (MWI), including sorption and redox
      reactions. Fundamental knowledge of these phenomena are often based on
      observations of ideal mineral-water systems, for example, studies of molecular
      scale reactions on single crystal faces or the surfaces of pure mineral powders.
      Much less is understood about MWI in natural environments, which typically have
      nanometer to micrometer scale secondary mineral coatings on the surfaces of
      primary mineral grains. We examined sediment grain coatings from a well
      characterized field site to determine the causes of rate limitations for arsenic
      (As) sorption and redox processes within the coatings. Sediments were obtained
      from the USGS field research site on Cape Cod, MA, and exposed to synthetic
      contaminated groundwater solutions. Uptake of As(III) and As(V) into the coatings
      was studied with a combination of electron microscopy and synchrotron techniques
      to assess concentration gradients and reactive processes, including electron
      transfer reactions. Transmission electron microscopy (TEM) and X-ray microprobe
      (XMP) analyses indicated that As was primarily associated with micrometer- to
      submicrometer aggregates of Mn-bearing nanoparticulate goethite. As(III)
      oxidation by this phase was observed but limited by the extent of exposed surface
      area of the goethite grains to the exterior of the mineral coatings. Secondary
      mineral coatings are potentially both sinks and sources of contaminants depending
      on the history of a contaminated site, and may need to be included explicitly in
      reactive transport models. 

PMID- 24041306
TI  - A highly conserved arginine residue of the chitosanase from Streptomyces sp. N174
      is involved both in catalysis and substrate binding.
AB  - BACKGROUND: Streptomyces sp. N174 chitosanase (CsnN174), a member of glycoside
      hydrolases family 46, is one of the most extensively studied chitosanases.
      Previous studies allowed identifying several key residues of this inverting
      enzyme, such as the two catalytic carboxylic amino acids as well as residues that
      are involved in substrate binding. In spite of the progress in understanding the
      catalytic mechanism of this chitosanase, the function of some residues highly
      conserved throughout GH46 family has not been fully elucidated. This study
      focuses on one of such residues, the arginine 42. RESULTS: Mutation of Arg42 into
      any other amino acid resulted in a drastic loss of enzyme activity. Detailed
      investigations of R42E and R42K chitosanases revealed that the mutant enzymes are
      not only impaired in their catalytic activity but also in their mode of
      interaction with the substrate. Mutated enzymes were more sensitive to substrate
      inhibition and were altered in their pattern of activity against chitosans of
      various degrees of deacetylation. Our data show that Arg42 plays a dual role in
      CsnN174 activity. CONCLUSIONS: Arginine 42 is essential to maintain the enzymatic
      function of chitosanase CsnN174. We suggest that this arginine is influencing the
      catalytic nucleophile residue and also the substrate binding mode of the enzyme
      by optimizing the electrostatic interaction between the negatively charged
      carboxylic residues of the substrate binding cleft and the amino groups of GlcN
      residues in chitosan.

PMID- 24041308
TI  - Direct evaluation of the hyperconjugative interactions in 1,1,1-trihaloethane
      (CH3CX3, X = F, Cl, and Br).
AB  - Following the computational strategy proposed by Mulliken in 1939 ( J. Chem.
      Phys. 1939, 7 (5), 339-352), when the concept of hyperconjugation was coined, we
      evaluated the hyperconjugative stabilization energy in 1,1,1-trihaloethane using
      the block-localized wave function (BLW) method. The BLW method is the simplest
      and most efficient variant of ab initio valence bond (VB) theory and can derive
      the strictly electron-localized state wave function self-consistently. The latter
      serves as a reference for the quantification of the electron delocalization
      effect in terms of the resonance theory. Computations show that the overall
      hyperconjugative interactions in 1,1,1-trihaloethane, dominated by sigma(CH) ->
      sigma'(CX) with minor contribution from sigma(CX) -> sigma'(CH), ranges from 9.59
      to 7.25 kcal/mol in the staggered structures and decreases in the order Br > Cl >
      F. This is in accord with the (1)H NMR spectra of CH3CX3. Notably, the
      hyperconjugation effect accounts for 35-40% of the rotation barriers in these
      molecules, which are dominated by the conventional steric repulsion. This is
      consistent with the recent findings with 1,2-difluoroethane (Freitas, Buhl, and
      O'Hagan. Chem. Comm. 2012, 48, 2433-2435) that the variation of (1)J(CF) with the
      FCCF torsional angle cannot be well explained by the hyperconjugation model

PMID- 24041307
TI  - Effect of the Tottori familial disease mutation (D7N) on the monomers and dimers
      of Abeta40 and Abeta42.
AB  - Recent experiments have shown that the mutation Tottori (D7N) alters the
      toxicity, assembly and rate of fibril formation of the wild type (WT) amyloid
      beta (Abeta) Abeta40 and Abeta42 peptides. We used all-atom molecular dynamics
      simulations in explicit solvent of the monomer and dimer of both alloforms with
      their WT and D7N sequences. The monomer simulations starting from a random coil
      and totaling 3 MUs show that the D7N mutation changes the fold and the network of
      salt bridges in both alloforms. The dimer simulations starting from the amyloid
      fibrillar states and totaling 4.4 MUs also reveal noticeable changes in terms of
      secondary structure, salt bridge, and topology. Overall, this study provides
      physical insights into the enhanced rate of fibril formation upon D7N mutation
      and an atomic picture of the D7N-mediated conformational change on Abeta40 and
      Abeta42 peptides. 

PMID- 24041309
TI  - Anticipated regret to increase uptake of colorectal cancer screening in Scotland
      (ARTICS): study protocol for a randomised controlled trial.
AB  - BACKGROUND: Colorectal cancer is the second leading cause of cancer deaths in the
      UK. Screening is key to early detection. The Scottish programme of colorectal
      cancer screening is running successfully, and involves all adults aged between 50
      and 74 years being invited to post back a faecal sample for testing every 2
      years. However, screening uptake is sub-optimal: for example rates for the period
      November 2009 to October 2011 ranged from just 39% for males living in the most
      deprived areas to 67% for least deprived females. Recent research has shown that
      asking people to consider the emotional consequences of not participating in
      screening (anticipated regret) can lead to a significant increase in screening
      uptake. METHODS/DESIGN: We will test a simple anticipated regret manipulation, in
      a large randomised controlled trial with 60,000 members of the general public.
      They will be randomly allocated to one of 3 arms, no questionnaire, control
      questionnaire or anticipated regret questionnaire. The primary outcome will be
      screening test kit return. Results will also be examined by demographic variables
      (age, gender, deprivation) as these are currently related to screening kit
      return. DISCUSSION: If this anticipated regret intervention leads to a
      significant increase in colorectal cancer screening kit returns, this would
      represent a rare example of a theoretically-driven, simple intervention that
      could result in earlier detection of colorectal cancer and many more lives saved.
      TRIAL REGISTRATION: Current Controlled trials: ISRCTN74986452.

PMID- 24041310
TI  - Engineering xylose metabolism in triacylglycerol-producing Rhodococcus opacus for
      lignocellulosic fuel production.
AB  - BACKGROUND: There has been a great deal of interest in fuel productions from
      lignocellulosic biomass to minimize the conflict between food and fuel use. The
      bioconversion of xylose, which is the second most abundant sugar present after
      glucose in lignocellulosic biomass, is important for the development of cost
      effective bioprocesses to fuels. Rhodococcus opacus PD630, an oleaginous
      bacterium, accumulates large amounts of triacylglycerols (TAGs), which can be
      processed into advanced liquid fuels. However, R. opacus PD630 does not
      metabolize xylose. RESULTS: We generated DNA libraries from a Streptomyces
      bacterium capable of utilizing xylose and introduced them into R. opacus PD630.
      Xsp8, one of the engineered strains, was capable of growing on up to 180 g L-1 of
      xylose. Xsp8 grown in batch-cultures derived from unbleached kraft hardwood pulp
      hydrolysate containing 70 g L-1 total sugars was able to completely and
      simultaneously utilize xylose and glucose present in the lignocellulosic
      feedstock, and yielded 11.0 g L-1 of TAGs as fatty acids, corresponding to 45.8%
      of the cell dry weight. The yield of total fatty acids per gram of sugars
      consumed was 0.178 g, which consisted primarily of palmitic acid and oleic acid.
      The engineered strain Xsp8 was introduced with two heterologous genes from
      Streptomyces: xylA, encoding xylose isomerase, and xylB, encoding xylulokinase.
      We further demonstrated that in addition to the introduction and the concomitant
      expression of heterologous xylA and xylB genes, there is another molecular target
      in the R. opacus genome which fully enables the functionality of xylA and xylB
      genes to generate the robust xylose-fermenting strain capable of efficiently
      producing TAGs at high xylose concentrations. CONCLUSION: We successfully
      engineered a R. opacus strain that is capable of completely utilizing high
      concentrations of xylose or mixed xylose/glucose simultaneously, and
      substantiated its suitability for TAG production. This study demonstrates that
      the engineered strain possesses a key trait of converters for lipid-based fuels
      production from lignocellulosic biomass.

PMID- 24041311
TI  - Observing graphene grow: catalyst-graphene interactions during scalable graphene
      growth on polycrystalline copper.
AB  - Complementary in situ X-ray photoelectron spectroscopy (XPS), X-ray
      diffractometry, and environmental scanning electron microscopy are used to
      fingerprint the entire graphene chemical vapor deposition process on
      technologically important polycrystalline Cu catalysts to address the current
      lack of understanding of the underlying fundamental growth mechanisms and
      catalyst interactions. Graphene forms directly on metallic Cu during the high
      temperature hydrocarbon exposure, whereby an upshift in the binding energies of
      the corresponding C1s XPS core level signatures is indicative of coupling between
      the Cu catalyst and the growing graphene. Minor carbon uptake into Cu can under
      certain conditions manifest itself as carbon precipitation upon cooling.
      Postgrowth, ambient air exposure even at room temperature decouples the graphene
      from Cu by (reversible) oxygen intercalation. The importance of these dynamic
      interactions is discussed for graphene growth, processing, and device
      integration. 

PMID- 24041312
TI  - 'Genipin' - the natural water soluble cross-linking agent and its importance in
      the modified drug delivery systems: an overview.
AB  - One of the popular approaches in controlling drug delivery from the polymeric
      carriers is suitably achieved by the inclusion of crosslinking agents into the
      formulations at different concentrations. Nevertheless, addition of the chemical
      crosslinkers such as glutaraldehyde, formaldehyde etc, used in the drug delivery
      systems causes very serious cytotoxic reactions. These chemical crosslinking
      agents did not offer any significant advantageous effects when compared to the
      natural crosslinking agents for instance genipin, which is quite less toxic,
      biocompatible and offers very stable crosslinked products. Based on the earlier
      reports the safety of this particular natural crosslinker is very well
      established, since it has been widely used as a Chinese traditional medicine for
      long-time, isolated from fruits of the plant Gardenia jasminoides Ellis. This
      concise article largely portrayed the value of this unique natural crosslinker,
      utilized in controlling the drug delivery from the various formulations. 

PMID- 24041313
TI  - The impact of the achievement motive on athletic performance in adolescent
      football players.
AB  - Researchers largely agree that there is a positive relationship between
      achievement motivation and athletic performance, which is why the achievement
      motive is viewed as a potential criterion for talent. However, the underlying
      mechanism behind this relationship remains unclear. In talent and performance
      models, main effect, mediator and moderator models have been suggested. A
      longitudinal study was carried out among 140 13-year-old football talents, using
      structural equation modelling to determine which model best explains how hope for
      success (HS) and fear of failure (FF), which are the aspects of the achievement
      motive, motor skills and abilities that affect performance. Over a period of half
      a year, HS can to some extent explain athletic performance, but this relationship
      is not mediated by the volume of training, sport-specific skills or abilities,
      nor is the achievement motive a moderating variable. Contrary to expectations, FF
      does not explain any part of performance. Aside from HS, however, motor abilities
      and in particular skills also predict a significant part of performance. The
      study confirms the widespread assumption that the development of athletic
      performance in football depends on multiple factors, and in particular that HS is
      worth watching in the medium term as a predictor of talent.

PMID- 24041314
TI  - Inhibition of inflammatory mediators and reactive oxygen and nitrogen species by
      some depsidones and diaryl ether derivatives isolated from Corynespora
      cassiicola, an endophytic fungus of Gongronema latifolium leaves.
AB  - In this study, some depsidones and diaryl ether derivatives isolated from
      Corynespora cassicola, a fungi endophyte of Gongronema latifolium, were assessed
      for their anti-inflammatory potentials. The isolated metabolites corynesidone A
      (1), corynesidone C (2), corynesidone D (3) and corynether A (4) were screened
      for their effects on tumour necrosis factor-alpha (TNF-alpha), inducible nitric
      oxide (iNO), and reactive oxygen species (ROS) and reactive nitrogen species
      (RNS) production by stimulated RAW264.7 macrophages. Concentration of 1, 2, 3 and
      4 up to 100 MUM did not remarkably affect the viability of treated macrophages.
      The compounds were found to cause a concentration-dependent decrease in
      lipopolysaccharide-induced TNF-alpha and iNO in RAW264.7 cells. Pre-treatment
      with 100 MUM of 1, 2, 3 and 4 suppressed iNO by as much as 96.28%, 95.71%, 78.14%
      and 73.28%; with IC(50) of 8.16, 9.49, 15.29 and 26.52 MUM, respectively.
      Similarly, pre-treatment with 100 MUM of 1, 2, 3 and 4 caused an inhibition of
      99.17%, 99.59%, 95.02% and 74.07% in the formation of iNO production,
      respectively, with IC(50) of 1.88, 3.99, 7.48 and 37.22 MUM. Treatment of with
      compounds 1-4 (10, 30 and 100 uM) followed by stimulation with phorbol 12
      myristate 13-acetate (1 uM) caused significant (p < 0.05) suppression of ROS/RNS
      evoked chemiluminescence of luminol by as much as 100.96 +/- 1.88%, 98.59 +/-
      1.38%, 87.35 +/- 1.41% and 79.22 +/- 0.30%, respectively at 100 uM. The depsidone
      derivatives (1-4) showed more potent inhibition of TNF-alpha and NO production
      and better scavenging ROS/RNS than the diaryl ether derivative (4). These
      chemical scaffolds can serve as suitable lead molecules for further development
      into novel anti-inflammatory and/or anti-cancer agents.

PMID- 24041315
TI  - synthesis of novel four armed PE-PCL grafted superparamagnetic and biocompatible
      nanoparticles.
AB  - Novel biocompatible polymer immobilized superparamagnetic nanoparticles (MNP) are
      prepared by grafting four armed pentaerythritol poly(epsilon-polycaprolactone)
      (PE-PCL) onto silane modified MNP. The MNPs are synthesized by hydrothermal
      process and its modification using (3-aminopropyl)trimethoxysilane (TMAS) coating
      is done by the sol-gel technique. The pentaerythritol (PE) initiated ring-opening
      polymerization (ROP) is carried out to prepare four armed PE-PCL. The reaction is
      shown to follow first order kinetics. The structure of PE-PCL is confirmed by NMR
      spectrum and MALDI-TOF analysis. The in situ grafting of PE-PCL onto modified MNP
      has been carried out by using 4,4'-methylenediphenyl diisocyanate (MDI) as an
      intermediate linker. The grafting density as determined by TGA analysis has been
      found to be significantly higher than previously reported linear PCL grafted MNPs
      in the literature. This leads to uniform dispersion of grafted MNPs which still
      is a challenging task in contemporary research. The effective dispersion of MNP
      into PE-PCL matrix is analyzed by HRTEM. The saturation magnetization of the PE
      PCL grafted MNPs is significantly high and this can be tailored further by
      varying the grafting density. The biocompatibility of polymer grafted
      nanoparticles is confirmed by MTT assay using HeLa cell line. The
      superparamagnetic and biocompatible novel PE-PCL grafted MNP so prepared would
      have manifold potential applications including in therapy and targeted drug
      delivery. 

PMID- 24041316
TI  - Split-brain, the right hemisphere, and art: fact and fiction.
AB  - The research studies of complete commissurotomy patients (split-brain) in Roger
      W. Sperry's psychobiology laboratory at Caltech, Pasadena, galvanized the
      scientific and intellectual world in the 1960s and 1970s. The findings had an
      important and enduring impact on brain research in countless areas. Interest in
      hemispheric specialization in particular was sparked by these studies and paved
      the way for countless discoveries. Right hemisphere specialization for
      visuospatial functions and facial processing was confirmed with these patients.
      The further unraveling of right-hemisphere cognition, the "mute" hemisphere, was
      a major goal in Sperry's laboratory, and much factual knowledge was learned that
      was not known previously. However, the linking of art and creativity with the
      right hemisphere was a nonempirically based inference made not by Sperry's lab
      but rather by others wishing to "assign" functional hemisphericity. The general
      assumption was that "art" is anchored in spatial cognition, that it is a
      nonverbal activity requiring imagery and thus must be controlled by the right,
      nonlanguage hemisphere. To this day, robust evidence that the right specializes
      in art expression or art perception is yet to be shown, if for no other reason
      than that art is not a single, unitary form of expression or cognition. The
      conjectured right hemisphere-art link turned into a popular story that filtered
      back into science, shaped future research of brain and art, and overlooked other
      avenues for insights. This chapter traces and explores this background. 

PMID- 24041317
TI  - Visual artistic creativity and the brain.
AB  - Creativity is the development of a new or novel understanding--insight that leads
      to the expression of orderly relationships (e.g., finding and revealing the
      thread that unites). Visual artistic creativity plays an important role in the
      quality of human lives, and the goal of this chapter is to describe some of the
      brain mechanisms that may be important in visual artistic creativity. The initial
      major means of learning how the brain mediates any activity is to understand the
      anatomy and physiology that may support these processes. A further understanding
      of specific cognitive activities and behaviors may be gained by studying patients
      who have diseases of the brain and how these diseases influence these functions.
      Physiological recording such as electroencephalography and brain imaging
      techniques such as PET and fMRI have also allowed us to gain a better
      understanding of the brain mechanisms important in visual creativity. In this
      chapter, we discuss anatomic and physiological studies, as well as
      neuropsychological studies of healthy artists and patients with neurological
      disease that have helped us gain some insight into the brain mechanisms that
      mediate artistic creativity.

PMID- 24041318
TI  - Artistic creativity, artistic production, and aging.
AB  - This chapter reviews the changes produced by age on various aspects of artistic
      painting, particularly creativity and actual production. Aging in trained
      painters is often accompanied by a decline in creativity, which in turn is due to
      the cognitive decline related to aging. It has been argued, however, that aging
      does not cause a decline, but only changes in style and content. The two views
      are not mutually exclusive, and we present examples illustrating both aspects. We
      also show that, in addition to cognitive changes, impairment of sensory organs,
      especially vision, and of the bones and joints, may also produce marked changes
      in an artist's production and style. We conclude by showing that finding ways to
      induce creativity in persons who do not consider themselves artists can be a way
      of stimulating creativity and contribute to successful aging. 

PMID- 24041319
TI  - Focal cerebral lesions and painting abilities.
AB  - Focal lesions such as strokes significantly affect painting production in the
      vast majority of artists. In particular, painters, when they resume painting,
      show changes in their painting style. In exceptional cases, there may be an
      apparent improvement in style, but in most cases, the changes represent nothing
      short of deterioration. This, however, varies according to the hemisphere
      affected. Painters with left-hemisphere lesions tend to show an inability to deal
      adequately with perspective and also tend to use simplified colors with fewer
      nuances. One often witnesses an evolution toward simpler, often "naive"
      techniques, and at times rigid geometric repetitive features. Painters with right
      hemisphere lesions also become unable to represent tridimensionality. In
      addition, their figures are often drawn in very summary fashion, with lack of
      coordination between volumes and space and a chromatic impoverishment; their main
      problem, however, is visuospatial, leading to neglect of the left side of the
      canvas. 

PMID- 24041320
TI  - Artistic creativity and dementia.
AB  - Artistic ability and creativity are defining characteristics of human behavior.
      Behavioral neurology, as a specialty, believes that even the most complex
      behaviors can be modeled and understood as the summation of smaller cognitive
      functions. Literature from individuals with specific brain lesions has helped to
      map out these smaller regions of cognitive abilities. More recently, models based
      on neurodegenerative conditions, especially from the frontotemporal dementias,
      have allowed for greater nuanced investigations into the various functional
      anatomies necessary for artistic behavior and possibly the underlying networks
      that promote creativity. 

PMID- 24041321
TI  - Deceiving the brain: pictures and visual perception.
AB  - Pictures deceive the brain: they provide distillations of objects or ideas into
      simpler shapes. They create the impression of representing that which cannot be
      presented. Even at the level of the photograph, the links between pictorial
      images (the contents of pictures) and objects are tenuous. The dimensions of
      depth and motion are missing from a pictorial image, and this alone introduces
      all manner of potential ambiguities. The history of art can be considered as
      exploring the missing link between image and object. Pictorial images can be
      spatialized or stylized; spatialized images (like photographs) generally share
      some of the projective characteristics of the object represented. Written words
      are also images but they do not resemble the objects they represent--they are
      stylized or conventional. Pictures can also be illusions--deceptions of vision so
      that what is seen does not necessarily correspond to what is physically
      presented. Most of visual science is now concerned with pictorial images--two
      dimensional displays on computer monitors. Is vision now the science of
      deception?

PMID- 24041322
TI  - The experience of art: insights from neuroimaging.
AB  - The experience of art is a complex one. It emerges from the interaction of
      multiple cognitive and affective processes. Neuropsychological and neuroimaging
      studies are revealing the broadly distributed network of brain regions upon which
      it relies. This network can be divided into three functional components: (i)
      prefrontal, parietal, and temporal cortical regions support evaluative judgment,
      attentional processing, and memory retrieval; (ii) the reward circuit, including
      cortical, subcortical regions, and some of its regulators, is involved in the
      generation of pleasurable feelings and emotions, and the valuation and
      anticipation of reward; and (iii) attentional modulation of activity in low-, mid
      , and high-level cortical sensory regions enhances the perceptual processing of
      certain features, relations, locations, or objects. Understanding how these
      regions act in concert to produce unique and moving art experiences and
      determining the impact of personal and cultural meaning and context on this
      network the biological foundation of the experience of art--remain future
      challenges. 

PMID- 24041323
TI  - On the electrophysiology of aesthetic processing.
AB  - One important method that can be applied for gaining an understanding of the
      underpinning of aesthetics in the brain is that of electrophysiology. Cognitive
      electrophysiology, in particular, allows the identification of components in a
      mental processing architecture. The present chapter reviews findings in the
      neurocognitive psychology of aesthetics, or neuroaesthetics, that have been
      obtained with the method of event-related brain potentials, as derived from the
      human electroencephalogram. The cognitive-perceptual bases as well as affective
      substages of aesthetic processing have been investigated and those are described
      here. The event-related potential method allows for the identification of mental
      processing modes in cognitive and aesthetic processing. It also provides an
      assessment of the mental chronometry of cognitive and affective stages in
      aesthetic appreciation. As the work described here shows, distinct processes in
      the brain are engaged in aesthetic judgments. 

PMID- 24041324
TI  - Mary Shelley's Frankenstein: exploring neuroscience, nature, and nurture in the
      novel and the films.
AB  - The story of Victor Frankenstein's quest to conquer death produced a legacy that
      has endured for almost 200 years. Powerful in its condemnation of the scientist's
      quest to achieve knowledge at any cost, Mary Shelley's Frankenstein is one of the
      most enduring novels of all time. It has never been out of print and has been
      translated to both stage and screen many times since its "birth." Numerous
      novels, short stories, and scripts have drawn upon Shelley's primary theme: the
      creation of a living organism from the dead, dying, and decaying body parts of
      human beings. Although Mary does not provide details of the animation process,
      particularly in her first edition, the process has been explored with a great
      deal of imagination and originality in the various cinematic portrayals of the
      story. Equally important as the theme of the scientist's quest for knowledge is
      the role that a creator plays in the life of its creation. Mary Shelley's novel
      pondered on how rejection would affect the offspring of such "unnatural" origins.
      In keeping with the "scientific" basis of the Creature's birth, cinematic
      portrayals attempted to provide a scientific rationale for the Creature's descent
      into madness and its evil behavior. From Robert Florey's initial script for the
      1931 film directed by James Whale to the more recent films and television series,
      an abnormal brain is considered to be the cause of the madness and malignity of
      the Creature. 

PMID- 24041325
TI  - Perception of emotion in abstract artworks: a multidisciplinary approach.
AB  - There is a long-standing and fundamental debate regarding how emotion can be
      expressed by fine art. Some artists and theorists have claimed that certain
      features of paintings, such as color, line, form, and composition, can
      consistently express an "objective" emotion, while others have argued that
      emotion perception is subjective and depends more on expertise of the observer.
      Here, we discuss two studies in which we have found evidence for consistency in
      observer ratings of emotion for abstract artworks. We have developed a stimulus
      set of abstract art images to test emotional priming, both between different
      painting images and between paintings and faces. The ratings were also used in a
      computational vision analysis of the visual features underlying emotion
      expression. Overall, these findings suggest that there is a strong bottom-up and
      objective aspect to perception of emotion in abstract artworks that may tap into
      basic visual mechanisms. 

PMID- 24041326
TI  - Art and brain: the relationship of biology and evolution to art.
AB  - Visual art, as with all other arts, is spontaneously created only by humans and
      is ubiquitously present to various extents in all societies today. Exploring the
      deep roots of art from cognitive, neurological, genetic, evolutionary,
      archaeological, and biological perspectives is essential for the full
      understanding of why we have art, and what art is about. The cognitive basis of
      art is symbolic, abstract, and referential thinking. However, archaeological
      markers of symbolic activity by early humans are not associated with art
      production. There is an enormously large time gap between the activity and the
      appearance of sporadic art by early Homo sapiens, and another large time delay
      before appearance of enduring practice of art. The aesthetic aspect of art is not
      considered to be the initial impetus for creating it. Instead, archaeological
      markers suggest that the early beginnings of art are associated with development
      of stratified societies where external visual identifiers by way of body
      ornaments and decorations were used. The major contributing forces for the
      consistency in art-making are presumed to be the formation of socioculture,
      intragroup cooperation, increased group size, survival of skillful artisans, and
      favorable demographic conditions. The biological roots of art are hypothesized to
      parallel aspects of our ancestry, specifically animal courtship displays, where
      signals of health and genetic quality are exhibited for inspection by potential
      mates. Viewers assess displayed art for talent, skill, communicative, and
      aesthetic-related qualities. Interdisciplinary discussions of art reflect the
      current approach to full understanding of the nature of art. 

PMID- 24041328
TI  - Design and synthesis of two porous metal-organic frameworks with nbo and agw
      topologies showing high CO2 adsorption capacity.
AB  - Two novel porous copper-based metal-organic frameworks with nbo and agw
      topologies have been designed and synthesized using tetracarboxylate and
      tricarboxylate ligands, respectively. They possess large surface areas and high
      CO2 adsorption capacities (up to 170 cm(3)/g or 7.59 mmol/g at 0  degrees C under
      ambient pressure). 

PMID- 24041329
TI  - The spatially asymmetric cost of memory load on visual perception: transient
      stimulus-centered neglect.
AB  - Recent evidence suggests that visual working memory (VWM) load reduces
      performance accuracy on a concurrent visual recognition task, particularly for
      objects presented in the left hemifield. It has also been shown that high VWM
      load causes suppression of activity in the right temporoparietal junction (TPJ).
      Given the resemblance of VWM load effects to symptoms of unilateral neglect
      (i.e., impaired perception on the left side and lesion to the right TPJ), we
      investigated whether VWM load effects are restricted to the left side of space or
      extend to object-centered reference frames. In other words, akin to object
      centered neglect, can high VWM load cause a perceptual cost in attending to the
      left side of the stimulus? We addressed this question using an object recognition
      task (Experiment 1) and a visual search task (Experiment 2) showing that this
      transient left-neglect can indeed be modulated by an object-centered frame of
      reference. These findings suggest that load-induced impairments of visual
      attention are spatially asymmetric and can emerge within multiple spatial
      reference frames. Therefore, the attentional consequences of high VWM load on
      conscious perception may serve as a useful model of unilateral perceptual
      neglect.

PMID- 24041331
TI  - Degree of certainty modulates anticipatory processes in real time.
AB  - In the present study, we investigated how degree of certainty modulates
      anticipatory processes using a modified spatial cuing task in which participants
      made an anticipatory hand movement with the computer mouse toward one of two
      probabilistic targets. A cue provided information of the location of the upcoming
      target with 100% validity (certain condition), 75% validity (semicertain
      condition) or gave no information of the location (uncertain condition). We found
      that the degree of certainty associated with the probabilistic precue on the
      upcoming target location affected the spatiotemporal characteristics of the
      anticipatory hand movements in a systematic way. In the case of semicertainty, we
      found evidence that the anticipatory processes were modulated in a way consistent
      with a model of graded probability matching biased toward certainty. In the case
      of uncertainty regarding two equally likely locations, we observed large between-
      and within-subject variability in the patterns of anticipatory hand movements,
      suggesting that individual differences in the strategies employed may become
      relevant when the likelihoods of response options are equal.

PMID- 24041330
TI  - The process of spoken word recognition in the face of signal degradation.
AB  - Though much is known about how words are recognized, little research has focused
      on how a degraded signal affects the fine-grained temporal aspects of real-time
      word recognition. The perception of degraded speech was examined in two
      populations with the goal of describing the time course of word recognition and
      lexical competition. Thirty-three postlingually deafened cochlear implant (CI)
      users and 57 normal hearing (NH) adults (16 in a CI-simulation condition)
      participated in a visual world paradigm eye-tracking task in which their
      fixations to a set of phonologically related items were monitored as they heard
      one item being named. Each degraded-speech group was compared with a set of age
      matched NH participants listening to unfiltered speech. CI users and the
      simulation group showed a delay in activation relative to the NH listeners, and
      there is weak evidence that the CI users showed differences in the degree of peak
      and late competitor activation. In general, though, the degraded-speech groups
      behaved statistically similarly with respect to activation levels.

PMID- 24041332
TI  - Direct observation of the low-spin Fe(III)-NO(radical) intermediate state during
      rebinding of NO to photodeligated ferric cytochrome c.
AB  - Nitrosylated ferric heme is autoreduced readily to the more stable Fe(II)-NO
      adduct, but it is stabilized in NO-carrier heme proteins where maintaining the
      Fe(III) oxidation state is crucial for efficient NO delivery. Density functional
      theory calculations by Lehnert and co-workers have shown that a NO-bound ferric
      model heme has a low-spin (LS) Fe(III)-NO(radical) state that might be critical
      for efficient NO transport by NO-carrier heme proteins. Recently, the elusive LS
      Fe(III)-NO(radical) state was observed as an electronic intermediate state during
      geminate rebinding (GR) of NO to ferric myoglobin (Mb(III)). Cytochrome c (Cytc),
      a ubiquitous heme protein, is useful for generalizing the presence of the LS
      Fe(III)-NO(radical) state. Photoexcitation dynamics of NO-bound ferric Cytc
      (Cytc(III)NO) was probed after excitation of Cytc(III)NO in D2O solution at 294 K
      with a 575 nm pulse using femtosecond vibrational spectroscopy. The time-resolved
      spectra displayed several weak absorption bands in the 1900-1800 cm(-1) range and
      a dominant bleach at 1917 cm(-1), the position of the absorption at equilibrium.
      Two absorptions, with 37 cm(-1) isotope shift of (15)NO, shifted toward higher
      energy and narrowed with an average time constant of 8 ps, indicating that they
      arose from thermally and/or vibrationally excited NO in the ground electronic
      state of Cytc(III)NO. Three absorption bands, showing 33 cm(-1) isotope shift of
      (15)NO and peaked at 1865, 1836, and 1807 cm(-1), were assigned to the deligated
      NO residing in the interior of the protein, to the rebound Cytc(III)NO in the LS
      Fe(III)-NO(radical) state, and to the vibrationally excited NO of Cytc(III)NO in
      the LS Fe(III)-NO(radical) state, respectively. The quantum yield for NO
      deligation of Cytc(III)NO by a 575 nm photon was 0.8 +/- 0.1. Most of the
      deligated NO showed non-exponential GR, and the GR kinetics was described by exp(
      (t/7 ps)(0.7)). Every rebound Cytc(III)NO formed the LS Fe(III)-NO(radical) state
      that relaxed into the ground state, with the relaxation kinetics described by
      exp(-(t/2.5 ps)(0.7)). The GR of NO to ferric Cytc was as fast as the thermal
      relaxation of hot heme, and the relaxation of the rebound Cytc(III)NO in the
      intermediate LS Fe(III)-NO(radical) state was faster than the thermal relaxation
      of hot heme, generating the rebound Cytc(III)NO in a thermally excited ground
      electronic state. For both Cytc(III)NO and Mb(III)NO, the relaxation rate of the
      LS Fe(III)-NO(radical) state was similar to the upper rate limit of the domed-to
      planar heme transition observed in NO-rebound ferrous-heme proteins, suggesting
      that the change in the Fe-NO bond length is coupled to the doming motion of the
      heme Fe. 

PMID- 24041333
TI  - Pannexin channels: the emerging therapeutic targets.
AB  - Intercellular communication plays a pivotal role in various physiological
      functions. This is mainly done through gap junctions and trans-membrane channels.
      The structural proteins forming these channels are different in vertebrates and
      invertebrates namely connexins and innexins respectively. Recently, a new class
      of proteins playing a crucial role in intercellular communication was discovered
      and named pannexins. They are found to have similar homology to innexins. Earlier
      they were also thought to form gap junctions and hemi channels on oppositional
      cell surfaces like connexins but later they were found to have different
      structure, location and function than connexins. Their main role is in the
      initiation and propagation of cellular calcium waves and ATP release. They are
      also considered an integral part of the greater purinergic and adrenergic
      receptor complexes. They are implicated in wide variety of biochemical and
      pathophysiological functions ranging from apoptosis, inflammation, ischemia,
      seizures and immune response; to paracrine signaling, vasodymanics, tumor
      genesis, cellular differentiation and development. Due to their ubiquitous
      distribution and involvement in myriad cellular functions, they are considered as
      potential therapeutic targets for diseases like hypertension, epilepsy and immune
      disorders. 

PMID- 24041334
TI  - Variable transmission lens influences on the dynamics of pupillary light
      reflexes.
AB  - This study examined the influence of liquid crystal variable transmission lenses
      on pupillary light reflexes in response to sudden bright light onset.
      Participants were exposed to bright light while pupil size was monitored using an
      eye tracker; eyewear was configured across four transition conditions: constant
      low-light filtering, constant high-light filtering, variable-light filtering in
      response to light detection and a control condition without eyewear. Before light
      onset, pupil diameter was largest in the high-filter condition, medium in the
      variable- and low-light filtering conditions and smallest in the control
      condition. Following light onset, the low-light filtering and control conditions,
      and the high-light filtering and variable-light filtering conditions converged
      over time. Critically, automatically transitioning between low- and high-light
      filtering reduced the magnitude (approximately 0.2 mm) and duration
      (approximately 360 ms) of the pupillary response relative to constant low-light
      filtering. 

PMID- 24041335
TI  - Proteomic and bioinformatic analysis of Trypanosoma cruzi chemotherapy and
      potential drug targets: new pieces for an old puzzle.
AB  - Chagas disease is endemic in Latin America and is caused by the protozoan
      hemoflagellate parasite Trypanosoma cruzi. Nowadays, it has also been
      disseminated to non-endemic countries due to the ease of global mobility. The
      nitroheterocycle benznidazole is currently used to treat this neglected tropical
      disease, although this drug causes severe side effects and has limited efficacy
      during the chronic phase of the disease. Proteomics and bioinformatics have
      recently become powerful tools in the identification of new drug targets. In the
      last decade, proteomic profiles of different T. cruzi forms under distinct
      experimental conditions were assessed. These reports have pointed to many
      potential drug targets, with ergosterol biosynthesis-related proteins and redox
      system enzymes being the most promising candidates. Nevertheless, the majority of
      the compounds active against T. cruzi still have unclear mechanisms of action,
      and most proteomic efforts have studied epimastigotes (the non-clinically
      relevant insect form of the parasite). Additional analyses with the clinically
      relevant parasite forms should be performed to identify proteins that actually
      bind drugs active against T. cruzi. Nonetheless, due to the known technical
      hurdles in generating such experimental data, bioinformatic approaches that
      integrate currently available data to generate additional knowledge will also be
      useful. Here, we review T. cruzi proteomics and describe the main chemoproteomic
      methods and their application to the identification of trypanosomatid drug
      targets. Finally, we discuss the potential benefits of more extensively
      integrating all proteomic data with other molecular databases via bioinformatic
      analyses to develop novel, viable strategies for alternative treatments of Chagas
      disease.

PMID- 24041336
TI  - Functions and mechanisms of green tea catechins in regulating bone remodeling.
AB  - Osteoporosis is caused by an imbalance in bone remodeling, a process involving
      bone-building osteoblasts and bone-resorptive osteoclasts. Excessive reactive
      oxygen species and inflammatory responses have been shown to stimulate
      differentiation and function of osteoclasts while inducing osteoblast apoptosis
      and suppressing osteoblastic proliferation and differentiation via extracellular
      signal-regulated kinases (ERK), ERK-dependent nuclear factor-kappaB and Wnt/beta
      catenin signaling pathways. The anti-oxidant and anti-inflammatory green tea
      catechins (GTC) have been shown to promote osteoblastogenesis, suppress
      osteoclastogenesis and stimulate the differentiation of mesenchymal stem cells
      into osteoblasts rather than adipocytes by modulating the signaling pathways.
      This paper reviews the pharmacokinetics and metabolism of GTC, their bone
      protective activities evidenced in in vitro and in vivo studies, and the limited
      clinical studies supporting these preclinical findings. In light of the physical,
      economical, and social burdens due to osteoporosis, easily accessible and
      affordable preventive measures such as GTC deserves further clinical studies
      prior to its clinical application. 

PMID- 24041338
TI  - [Particle pollution effects on the risk of cardiovascular diseases].
AB  - The effects of air pollution on health are quite well-documented and the
      influence of particulate pollution on morbidity and mortality from myocardial
      infarction and stroke is increasingly evident. The objective of this literature
      review is to identify and synthesize articles on the impact of air pollution by
      PM10 and PM2.5 of myocardial infarction and stroke. A total of 14 studies were
      reported on the effects of PM10 and five on the effects of PM2.5. Nine out of 14
      studies for PM10 and two studies of five for PM2.5 have found a significant
      association with myocardial infarction and/or stroke. Particle composition
      according to location, study period and population must be considered in
      interpreting the results on the health effects of air pollution. The integration
      of these elements is important for decision making in tune with social and
      economic conditions specific to each environment.

PMID- 24041337
TI  - Vitamin D supplementation in older people (VDOP): Study protocol for a randomised
      controlled intervention trial with monthly oral dosing with 12,000 IU, 24,000 IU
      or 48,000 IU of vitamin D3.
AB  - The randomised, double blind intervention trial 'Optimising Vitamin D Status in
      Older People' (VDOP) will test the effect of three oral dosages of vitamin D
      given for one year on bone mineral density (BMD) and biochemical markers of
      vitamin D metabolism, bone turnover and safety in older people. VDOP is funded by
      Arthritis Research UK, supported through Newcastle University and MRC Human
      Nutrition Research and sponsored by the Newcastle upon Tyne Hospitals NHS
      Foundation Trust.a BACKGROUND: Vitamin D insufficiency is common in older people
      and may lead to secondary hyperparathyroidism, bone loss, impairment of muscle
      function and increased risk of falls and fractures. Vitamin D supplementation
      trials have yielded conflicting results with regard to decreasing rates of bone
      loss, falls and fractures and the optimal plasma concentration of 25 hydroxy
      vitamin D (25OHD) for skeletal health remains unclear. METHOD/DESIGN: Older (>=70
      years) community dwelling men and women are recruited through General Practices
      in Northern England and 375 participants are randomised to take 12,000
      international units (IU), 24,000 IU or 48,000 IU of vitamin D3 orally each month
      for one year starting in the winter or early spring. Hip BMD and anthropometry
      are measured at baseline and 12 months. Fasting blood samples are collected at
      baseline and three-month intervals for the measurement of plasma 25OHD,
      parathyroid hormone (PTH), biochemical markers of bone turnover and biochemistry
      to assess the dose-response and safety of supplementation. Questionnaire data
      include falls, fractures, quality of life, adverse events and outcomes,
      compliance, dietary calcium intake and sunshine exposure. DISCUSSION: This is the
      first integrated vitamin D supplementation trial in older men and women using a
      range of doses given at monthly intervals to assess BMD, plasma 25OHD, PTH and
      biochemical markers of bone turnover and safety, quality of life and physical
      performance. We aim to investigate the vitamin D supplementation and plasma 25OHD
      concentration required to maintain bone health and to develop a set of
      biochemical markers that reflects the effect of vitamin D on bone. This will aid
      future studies investigating the effect of vitamin D supplementation on fracture
      risk.#ISRCTN 35648481 (assigned 16 August 2012), EudraCT 2011-004890-10.

PMID- 24041339
TI  - [Pseudoaneurysm of the left ventricle in young patients: A propos of three
      cases].
AB  - Pseudoaneurysm of the left ventricle is a rare late complication of myocardial
      infarction. So-called non-coronary forms have been described in young people. In
      this context, we report three cases. Mr. M.B., aged 20, consulted for chest pain
      associated with palpitations. Cardiovascular examination found a pulsatile,
      expanding precordial bulging and a mesocardiac systolo-diastolic murmur. We noted
      a sinus rhythm with ventricular extrasystoles on ECG. The chest radiograph showed
      cardiomegaly and aneurysmal deformation of the left lower heart border. Doppler
      echocardiography showed a large left ventricular apical pseudoaneurysm. Mrs.
      O.B., aged 23, was admitted for biventricular heart failure and in whom the
      examination found a systolic murmur in the apical area. ECG showed a regular
      sinus tachycardia, left atrial and ventricular hypertrophy. The chest radiograph
      showed cardiomegaly and aneurysmal deformation of left middle and lower heart
      borders. Doppler echocardiography showed a large left ventricular apical
      pseudoaneurysm. Mr. I.S., aged 24, admitted for the management of congestive
      heart failure. The patient had non-specific laboratory inflammatory signs, a
      sinus tachycardia and extrasystoles on the ECG. Chest radiography showed a
      discontinuation at the posterior arch of the sixth rib, a cardiomegaly and a
      neurismal dilatation of the left lower heart border. Doppler echocardiography
      showed a large apical pseudoaneurysm of the left ventricle. 

PMID- 24041340
TI  - Advancing pediatric patient-reported outcome assessment.

PMID- 24041341
TI  - Genetic screening for the predisposition to venous thromboembolism: a cost
      utility analysis of clinical practice in the Italian health care system.
AB  - OBJECTIVES: In the Italian health care system, genetic tests for factor V Leiden
      and factor II are routinely prescribed to assess the predisposition to venous
      thromboembolism (VTE) of women who request oral contraception. With specific
      reference to two subpopulations of women already at risk (i.e., familial history
      or previous event of VTE), the study aimed to assess whether current screening
      practices in Italy are cost-effective. METHODS: Two decisional models accrued
      costs and quality-adjusted life-years (QALY) annually from the perspective of the
      National Health Service. The two models were derived from a decision analysis
      exercise concerning testing practices and consequent prescribing behavior for
      oral contraception conducted with 250 Italian gynecologists. Health care costs
      were compiled on the basis of 10-year hospital discharge records and the
      activities of a thrombosis center. Whenever possible, input data were based on
      the Italian context; otherwise, the data were taken from the international
      literature. RESULTS: Current testing practices on women with a familial history
      of VTE generate an incremental cost-effectiveness ratio of ?72,412/QALY, which is
      well above the acceptable threshold of cost-effectiveness of ?40,000 to
      ?50,000/QALY. In the case of women with a previous event of VTE, the most
      frequently used testing strategy is cost-ineffective and leads to an overall loss
      of QALY. CONCLUSIONS: This study represents the first attempt to conduct a cost
      utility analysis of genetic screening practices for the predisposition to VTE in
      the Italian setting. The results indicate that there is an urgent need to better
      monitor the indications for which tests for factor V Leiden and factor II are
      prescribed.

PMID- 24041342
TI  - Cost-effectiveness of baseline low-dose computed tomography screening for lung
      cancer: the Israeli experience.
AB  - OBJECTIVE: Reduced mortality with low-dose computed tomography (LDCT) lung cancer
      screening was demonstrated in a large randomized controlled study of high-risk
      individuals. Cost-effectiveness must be assessed before routine LDCT screening is
      considered. We aimed to evaluate the cost-effectiveness of LDCT lung cancer
      screening in Israel. METHODS: A decision analytic framework was used to evaluate
      the decision to screen or not screen from the health system perspective. The
      screening arm included 842 moderate-to-heavy smokers aged 45 years or older,
      screened at Hadassah-Hebrew University Medical Center from 1998 to 2004. In the
      usual-care arm, stage distribution and stage-specific life expectancy were
      obtained from the Israel National Cancer Registry data for 1994 to 2006. Lifetime
      stage-specific costs were estimated from medical records of patients diagnosed
      and treated at Hadassah Medical Center in the period 2003 to 2004. The analysis
      considered possible biases-lead time, overdiagnosis, and self-selection. Cost per
      quality-adjusted-life-year (QALY) gained by screening was estimated. RESULTS:
      Base-case incremental cost per QALY gained was $1464 (2011 prices). Extensive
      sensitivity analysis affirmed the low cost per QALY gained. The cost per QALY
      gained is lower than $10,000 with probability 0.937 and is lower than $20,000
      with probability 0.978. CONCLUSIONS: Our analysis suggests that baseline LDCT
      lung cancer screening in Israel presents a good value for the money and should be
      considered for inclusion in the National List of Health Services financed
      publicly.

PMID- 24041343
TI  - Program-specific cost-effectiveness analysis: breast cancer screening policies
      for a safety-net program.
AB  - BACKGROUND: Every Woman Counts (EWC), a California breast cancer screening
      program, faced challenging budget cutbacks and policy choices. METHODS: A
      microsimulation model evaluated costs, outcomes, and cost-effectiveness of EWC
      program mammography policy options on coverage for digital mammography (which has
      a higher cost than film mammography but recent legislation allowed reimbursement
      at the lower film rate); screening eligibility age; and screening frequency.
      Model inputs were based on analyses of program claims data linked to California
      Cancer Registry data, Surveillance, Epidemiology, and End Results data, and the
      Medi-Cal literature. Outcomes included number of procedures, cancers, cancer
      deaths, costs, and incremental cost per life-year. RESULTS: Projected model
      outcomes matched program data closely. With restrictions on the number of clients
      screened, strategies starting screening at age 40 years were dominated (not cost
      effective). This finding was highly robust in sensitivity analyses. Compared with
      no screening, biennial film mammography for women aged 50 to 64 years was
      projected to reduce 15-year breast cancer mortality by nearly 7.8% at $18,999 per
      additional life-year, annual film mammography was $106,428 per additional life
      year, and digital mammography $180,333 per additional life-year. This more
      effective, more expensive strategy was projected to reduce breast cancer
      mortality by 8.6%. Under equal mammography reimbursement, biennial digital
      mammography beginning at age 50 years was projected to decrease 15-year breast
      cancer mortality by 8.6% at an incremental cost per additional life-year of
      $17,050. CONCLUSIONS: For the EWC program, biennial screening mammography
      starting at age 50 years was the most cost-effective strategy. The impact of
      digital mammography on life expectancy was small. Program-specific cost
      effectiveness analysis can be completed in a policy-relevant time frame to assist
      policymakers faced with difficult program choices.

PMID- 24041344
TI  - Cost-utility of metal-on-metal hip resurfacing compared to conventional total hip
      replacement in young active patients with osteoarthritis.
AB  - BACKGROUND: Metal-on-metal hip resurfacing arthroplasty (MoM HRA) has emerged as
      an alternative to total hip arthroplasty (THA) for younger active patients with
      osteoarthritis (OA). Birmingham hip resurfacing is the most common MoM HRA in
      Alberta, and is therefore compared with conventional THA. OBJECTIVE: The
      objective of this study was to estimate the expected cost-utility of MoM HRA
      versus THA, in younger patients with OA, using a decision analytic model with a
      15-year time horizon. METHODS: A probabilistic Markov decision analytic model was
      constructed to estimate the expected cost per quality-adjusted life-year (QALY)
      of MoM HRA versus THA from a health care payer perspective. The base case
      considered patients with OA aged 50 years; men comprised 65.9% of the cohort.
      Sensitivity analyses evaluated cohort age, utility values, failure probabilities,
      and treatment costs. Data were derived from the Hip Improvement Project and the
      Hip and Knee Replacement Pilot databases in Alberta, the 2010 National Joint
      Replacement Registry of the Australian Orthopaedic Association, and the
      literature. RESULTS: In the base case, THA was dominated by MoM HRA (incremental
      mean costs of -$583 and incremental mean QALYs of 0.079). In subgroup analyses,
      THA remained dominated when cohort age was 40 years instead of 50 years or when
      only men were assessed. THA dominated when the cohort age was 60 years or when
      only women were assessed. Results were sensitive to utilities, surgery costs, and
      MoM HRA revision and conversion probabilities. At a willingness-to-pay of Can
      $50,000/QALY, there was a 58% probability that MoM HRA is cost-effective.
      CONCLUSIONS: The results show that, on average, MoM HRA was preferred to THA for
      younger and male patients, but THA is still a reasonable option if the patient or
      clinician prefers given the small absolute differences between the options and
      the confidence ellipses around the cost-effectiveness estimates.

PMID- 24041346
TI  - Economic assessment of an anti-HCV screening program in Italy.
AB  - BACKGROUND: The progression of hepatitis C virus (HCV) disease usually occurs
      over a 10-year period. HCV-related complications as well as the highly
      debilitating effects on patients represent a significant item of expenditure for
      the National Health Service. Early detection of HCV infection is an excellent
      opportunity to improve patients' quality of life and to rationalize resource
      allocation. OBJECTIVE: The aim of this study was to provide a cost-effectiveness
      evaluation of an anti-HCV screening program in the Italian National Health
      Service perspective. METHODS: We built a Markov model made up of two arms. The
      ''Test Strategy'' arm involves a screening program based on the enzyme
      immunoassay for detection of antibodies as first-level test and the research of
      HCV RNA as second-level detection; patients with positive test results are
      treated with peg-interferon alfa in combination with ribavirine. Parameters were
      derived from the literature and validated through experts' opinion. Costs and
      benefits were discounted by 3.5%. Results were expressed as cost/quality-adjusted
      life-year (QALY) gained through the screening program compared with the treatment
      of symptomatic patients. Deterministic and probabilistic sensitivity analysis was
      performed. RESULTS: The incremental cost-effectiveness ratio of the ''Test
      Strategy'' is ?5171/QALY, definitively below the cost/QALY of other approved
      treatments in Italy. Model results turned out as sensitive to the age of the
      target population, the prevalence of HCV infection, and the time horizon adopted.
      CONCLUSIONS: The anti-HCV screening program is a valid health-related investment
      improving patients' quality of life and survival with an acceptable expenditure
      increase for the National Health Service.

PMID- 24041348
TI  - The development and validation of a multidimensional sum-scaling questionnaire to
      measure patient-reported outcomes in acute respiratory tract infections in
      primary care: the acute respiratory tract infection questionnaire.
AB  - OBJECTIVE: Patient-reported outcomes are seldom validated measures in clinical
      trials of acute respiratory tract infections (ARTIs) in primary care. We
      developed and validated a patient-reported outcome sum-scaling measure to assess
      the severity and functional impacts of ARTIs. METHODS: Qualitative interviews and
      field testing among adults with an ARTI were conducted to ascertain a high degree
      of face and content validity of the questionnaire. Subsequently, a draft version
      of the Acute Respiratory Tract Infection Questionnaire (ARTIQ) was statistically
      validated by using the partial credit Rasch model to test dimensionality,
      objectivity, and reliability of items. Test of known groups' validity was
      conducted by comparing participants with and without an ARTI. RESULTS: The final
      version of the ARTIQ consisted of 38 items covering five dimensions (Physical
      upper, Physical-lower, Psychological, Sleep, and Medicine) and five single items.
      All final dimensions were confirmed to fit the Rasch model, thus enabling sum
      scaling of responses. The ARTIQ scores in participants with an ARTI were
      significantly higher than in those without ARTI (known groups' validity).
      CONCLUSION: A self-administered, multidimensional, sum-scaling questionnaire with
      high face and content validity and adequate psychometric properties for assessing
      severity and functional impacts from ARTIs in adults is available to clinical
      trials and audits in primary care.

PMID- 24041345
TI  - Lifetime cost-effectiveness of trial of labor after cesarean in the United
      States.
AB  - OBJECTIVE: To estimate the cost-effectiveness of a trial of labor after one
      previous cesarean (TOLAC) when incorporating long-term events and outcomes.
      METHODS: A Markov model comparing TOLAC with elective repeat cesarean delivery
      (ERCD) was developed for a hypothetical cohort with no contraindication to a
      TOLAC. Women were selected from a prospective study to derive probability
      estimates for potential events through three subsequent pregnancies.
      Probabilities for cerebral palsy and stress urinary incontinence, cost data, and
      quality-adjusted life-years (QALYs) were obtained from the literature. The
      primary outcome was cost-effectiveness measured as the marginal cost per QALY
      gained, with a $50,000 threshold per QALY used to define cost-effectiveness.
      RESULTS: The TOLAC strategy dominated the ERCD strategy at baseline, with $164.2
      million saved and 500 QALYs gained per 100,000 women. The model was sensitive to
      six variables: the probability of uterine rupture and successful TOLAC among
      women with no prior vaginal delivery, the frequency of stress urinary
      incontinence, and the costs of failed TOLAC, successful TOLAC, and ERCD. When the
      probability of TOLAC success was at the base value, 67.2%, TOLAC was preferred if
      the probability of uterine rupture was 3.1% or less. When the probability of
      uterine rupture was at the base value, 0.8%, the TOLAC strategy was preferred as
      long as the probability of success was 47.2% or more. Probabilistic sensitivity
      analysis confirmed the base-case analysis. CONCLUSIONS: Under baseline
      circumstances, TOLAC is less expensive and more effective than an ERCD when
      considering long-term consequences when the likelihood of success is 47.2% or
      more.

PMID- 24041347
TI  - Cost-effectiveness of boceprevir in patients previously treated for chronic
      hepatitis C genotype 1 infection in the United States.
AB  - OBJECTIVES: The phase 3 trial, Serine Protease Inhibitor Boceprevir and
      PegIntron/Rebetol-2 (RESPOND-2), demonstrated that the addition of boceprevir
      (BOC) to peginterferon-ribavirin (PR) resulted in significantly higher rates of
      sustained virologic response (SVR) in previously treated patients with chronic
      hepatitis C virus (HCV) genotype-1 infection as compared with PR alone. We
      evaluated the cost-effectiveness of treatment with BOC in previously treated
      patients with chronic hepatitis C in the United States using treatment-related
      data from RESPOND-2 and PROVIDE studies. METHODS: We developed a Markov cohort
      model to project the burden of HCV disease, lifetime costs, and quality-adjusted
      life-years associated with PR and two BOC-based therapies-response-guided therapy
      (BOC/RGT) and fixed-duration therapy for 48 weeks (BOC/PR48). We estimated
      treatment-related inputs (efficacy, adverse events, and discontinuations) from
      clinical trials and obtained disease progression rates, costs, and quality-of
      life data from published studies. We estimated the incremental cost-effectiveness
      ratio (ICER) for BOC-based regimens as studied in RESPOND-2, as well as by
      patient's prior response to treatment and the IL-28B genotype. RESULTS: BOC-based
      regimens were projected to reduce the lifetime incidence of liver-related
      complications by 43% to 53% in comparison with treatment with PR. The ICER of
      BOC/RGT in comparison with that of PR was $30,200, and the ICER of BOC/PR48 in
      comparison with that of BOC/RGT was $91,500. At a willingness-to-pay threshold of
      $50,000, the probabilities of BOC/RGT and BOC/PR48 being the preferred option
      were 0.74 and 0.25, respectively. CONCLUSIONS: In patients previously treated for
      chronic HCV genotype-1 infection, BOC was projected to increase quality-adjusted
      life-years and reduce the lifetime incidence of liver complications. In addition,
      BOC-based therapies were projected to be cost-effective in comparison with PR
      alone at commonly used willingness-to-pay thresholds.

PMID- 24041349
TI  - Benchmarks for interpretation of score differences on the SF-36 health survey for
      patients with diabetes.
AB  - OBJECTIVE: To estimate clinical and social benchmarks for interpretation of score
      differences on the Short-Form 36 Health Survey, and apply these benchmarks to
      populations with diabetes mellitus (DM). METHODS: Using survival and logistic
      regression models, we reanalyzed data from three US cohorts: the Medical Outcomes
      Study (N = 3,445; 541 patients with DM), the Medicare Health Outcomes Survey (N =
      78,183; 16,388 patients with DM), and the QualityMetric 2009 Norming Study (N =
      4,040; 580 patients with DM). Outcome variables were mortality, hospitalization,
      current inability to work, and loss of ability to work. RESULTS: Benchmarks were
      robust across disease groups, but varied according to age and score level. A 1
      point lower score on the Physical Function, General Health, and Physical
      Component Summary scales was associated with a 1.05 to 1.09 relative risk (RR) of
      mortality for the typical patient with DM, with stronger associations in the
      younger age groups. For several scales (Physical Function, Role Physical, Bodily
      Pain, General Health, Vitality, Social Function, and Role Emotional), the
      associations with mortality also depended on score level, with stronger
      associations in the lower score ranges (i.e., patients in worse health). A 1
      point lower score on the Physical Function, Role Physical, Bodily Pain, General
      Health, Vitality, Social Function, and Physical Component Summary scales implied
      a 1.02 to 1.04 RR of hospitalization, a 1.07 to 1.12 RR of being unable to work,
      and a 1.04 to 1.07 RR of losing the ability to work. CONCLUSIONS: A 1-point lower
      score on selected Short-Form 36 Health Survey scales is associated with an excess
      risk of up to 9% for mortality and 12% for inability to work.

PMID- 24041350
TI  - Psychometric properties and measurement equivalence of the English and Chinese
      versions of the functional assessment of cancer therapy-cognitive in Asian
      patients with breast cancer.
AB  - OBJECTIVE: This study was designed to examine the psychometric properties and
      measurement equivalence of the English and Chinese versions of the Functional
      Assessment of Cancer Therapy-Cognitive Function (Version 3) (FACT-Cog) in
      multiethnic Asian patients with breast cancer. METHODS: This prospective study
      involved patients with breast cancer from the National Cancer Centre Singapore.
      The concurrent validity of the FACT-Cog was assessed according to its strength of
      correlation with the validated European Organization for Research and Treatment
      of Cancer Quality of Life Core Questionnaire 30 cognitive functioning scale, and
      its association with fatigue, global health status, and anxiety. The known-group
      validity was assessed on the basis of receipt of chemotherapy. Factor analysis
      was conducted to ascertain the one-factor structure of each cognitive domain. The
      reliability was evaluated by using Cronbach's alpha and intraclass correlation
      coefficient within the cognitive domains. Multiple regression analyses were
      performed to compare the total scores between the two language versions,
      adjusting for covariates. RESULTS: A total of 185 English-speaking and 143
      Chinese-speaking patients were recruited. Both the English and Chinese FACT-Cog
      total scores correlated strongly with the European Organization for Research and
      Treatment of Cancer Quality of Life Core Questionnaire 30 cognitive functioning
      scale scores (r = 0.725 and 0.646), whereas correlations with fatigue, anxiety,
      and global health status were weak to moderate (|r| = 0.376-0.589). Regarding the
      known-group validity, more severe perceived cognitive disturbance was observed
      among patients receiving chemotherapy than among those who were not for both
      versions (P = .010 and .008, respectively). Internal consistencies within the
      cognitive domains were high (Cronbach's alpha 0.707-0.929), and test-retest
      reliability was satisfactory for both versions (intraclass correlation
      coefficient 0.762 and 0.697). The measurement equivalence between the English and
      Chinese versions was established for all domains except the multitasking domain.
      CONCLUSION: The English and Chinese versions of the FACT-Cog are valid, reliable,
      and equivalent for clinical and research use.

PMID- 24041351
TI  - Item-level psychometric properties for a new patient-reported psoriasis symptom
      diary.
AB  - OBJECTIVES: This research evaluated the psychometric properties of a new
      Psoriasis Symptom Diary, identified diary responder definitions for use in
      determining whether a patient has experienced clinically meaningful change, and
      refined diary item content for use in future clinical trials. METHODS: The
      Psoriasis Symptom Diary was administered in a phase 2 clinical trial of AIN457 to
      US adult outpatients (N = 172) with physician-diagnosed moderate to severe
      chronic plaque-type psoriasis. Participant compliance with daily diary
      administration and item score variability, reliability, construct and
      discriminant validity, sensitivity to change, and interpretation were all
      evaluated. RESULTS: Participants completed 94% of scheduled diary assessments
      across 12 study weeks. Diary items were generally normally distributed, and no
      floor or ceiling effects were observed. Item reliability (reproducibility) was
      acceptable (intraclass correlation coefficients > 0.80), with an exception for
      one item (skin color). At week 12, items significantly related to criterion
      measures as predicted (Psoriasis Area and Severity Index r = 0.27-0.57;
      Investigator's Global Assessment r = 0.25-0.59), with the exception of items that
      measured skin color and difficulty using hands. Most items generated change
      scores that were synchronous to changes as measured by the Psoriasis Area and
      Severity Index, Investigator's Global Assessment, Dermatology Life Quality Index
      (r > 0.37), as well as the Patient Global Impression of Change. Responders
      experienced a 2- to 3-point and 3- to 5-point change in item scores for minimal
      and large improvements, respectively. Four items that did not perform well were
      dropped from the diary. CONCLUSIONS: The 16-item Psoriasis Symptom Diary
      demonstrated favorable psychometric properties and is a brief, useful tool for
      measuring patient-based symptoms and the impact of chronic plaque psoriasis.

PMID- 24041352
TI  - Exploring the consistency of the SF-6D.
AB  - OBJECTIVE: The six-dimensional health state short form (SF-6D) was designed to be
      derived from the short-form 36 health survey (SF-36). The purpose of this
      research was to compare the SF-6D index values generated from the SF-36 (SF-6DSF
      36) with those obtained from the SF-6D administered as an independent instrument
      (SF-6DInd). The goal was to assess the consistency of respondents' answers to
      these two methods of deriving the SF-6D. METHODS: Data were obtained from a
      sample of the Portuguese population (n = 414). Agreement between the instruments
      was assessed on the basis of a descriptive system and their indexes. The analysis
      of the descriptive system was performed by using a global consistency index and
      an identically classified index. Agreement was also explored by using correlation
      coefficients. Parametric tests were used to identify differences between the
      indexes. Regression models were estimated to understand the relationship between
      them. RESULTS: The SF-6DInd generates higher values than does the SF-6DSF-36.
      There were significant differences between the indexes across sociodemographic
      groups. There was a significant ceiling effect in the SF-6DInd but not in the SF
      6DSF-36. The correlation between the indexes was high but less than what was
      anticipated. The global consistency index identified the dimensions with larger
      differences. Considerable differences were found in two dimensions, possibly as a
      result of different item contexts. Further research is needed to fully understand
      the role of the different layouts and the length of the questionnaires in the
      respondents' answers. CONCLUSIONS: The results show that as the SF-6D was
      designed to derive utilities from the SF-36 it should be used in this way and not
      as an independent instrument.

PMID- 24041353
TI  - Modeling SF-6D Hong Kong standard gamble health state preference data using a
      nonparametric Bayesian method.
AB  - OBJECTIVES: This article reports on the findings from applying a recently
      described approach to modeling health state valuation data and the impact of the
      respondent characteristics on health state valuations. The approach applies a
      nonparametric model to estimate a Bayesian six-dimensional health state short
      form (derived from short-form 36 health survey) health state valuation algorithm.
      METHODS: A sample of 197 states defined by the six-dimensional health state short
      form (derived from short-form 36 health survey)has been valued by a
      representative sample of the Hong Kong general population by using standard
      gamble. The article reports the application of the nonparametric model and
      compares it to the original model estimated by using a conventional parametric
      random effects model. The two models are compared theoretically and in terms of
      empirical performance. RESULTS: Advantages of the nonparametric model are that it
      can be used to predict scores in populations with different distributions of
      characteristics than observed in the survey sample and that it allows for the
      impact of respondent characteristics to vary by health state (while ensuring that
      full health passes through unity). The results suggest an important age effect
      with sex, having some effect, but the remaining covariates having no discernible
      effect. CONCLUSIONS: The nonparametric Bayesian model is argued to be more
      theoretically appropriate than previously used parametric models. Furthermore, it
      is more flexible to take into account the impact of covariates.

PMID- 24041354
TI  - Responsiveness of the testing morbidities index in colonoscopy.
AB  - OBJECTIVES: The Testing Morbidities Index (TMI) was developed to measure the
      effects of any diagnostic or screening procedure on health-related quality of
      life (HRQOL); it includes seven domains incorporating mental and physical aspects
      before, during, and after testing. To add to prior work on the validity of the
      TMI classification, responsiveness of a summated scale version was evaluated in
      71 colonoscopy patients. Further data on construct validity were also obtained.
      METHODS: Patients enrolled in the study when scheduling colonoscopy days to weeks
      beforehand. The baseline survey included the EuroQol five-dimensional (EQ-5D)
      questionnaire with five levels in each attribute (EQ-5D-5L questionnaire) and its
      visual analogue scale (VAS) assessment (EQ-VAS), the Short Form 12 version 2 (SF
      12v2) component summary scores and six-dimensional health state short-form
      (derived from the short-form 12v2 health survey [SF-6D] utilities), and an
      original construct-specific VAS (CS-VAS) for usual HRQOL using utility scale
      anchors. The TMI's highest possible summated score (all best levels) served as
      its baseline. Survey data were generally obtained by telephone interview. A
      postprocedure survey was given to patients after colonoscopy and interviews
      conducted as soon as possible after the day of the procedure. The postprocedure
      survey included the SF-12v2/SF-6D, EQ-5D questionnaire instruments, TMI items,
      and a CS-VAS incorporating the overall HRQOL effects of colonoscopy. RESULTS:
      Standardized response means showed greatest responsiveness by the TMI (-1.52)
      followed by the CS-VAS instruments (-0.42). The EQ-5D-5L questionnaire, the EQ
      VAS, and the SF-12 component summaries were unresponsive, and the SF-6D was
      minimally responsive (-0.05). Correlation of the post-CS-VAS with the TMI was
      substantial (r = -0.52), suggesting TMI construct validity. Moderate to strong
      correlation of the baseline CS-VAS with standard indexes was observed (r = 0.54
      0.81). CONCLUSION: The TMI appears responsive and exhibits further evidence of
      construct validity.

PMID- 24041355
TI  - Treatment dynamics of newly marketed drugs and implications for comparative
      effectiveness research.
AB  - OBJECTIVES: Clinicians and payers require rapid comparative effectiveness (CE)
      evidence generation to inform decisions for new drugs. We empirically assessed
      treatment dynamics of newly marked drugs and their implications for conducting CE
      research. METHODS: We used claims data to evaluate five drug-outcome pairs: 1)
      raloxifene (vs. alendronate) and fracture; 2) risedronate (vs. alendronate) and
      fracture; 3) simvastatin plus ezetimibe fixed-dose combination (simvastatin +
      ezetimibe) (vs. simvastatin alone) and cardiovascular events; 4) rofecoxib (vs.
      nonselective nonsteroidal anti-inflammatory drugs [ns-NSAIDs]) and myocardial
      infarction; and 5) rofecoxib (vs. ns-NSAIDS) and gastrointestinal bleed. We
      examined utilization dynamics in the early marketing period, including evolving
      utilization patterns, outcome risk among those treated with new versus
      established drugs, and prior treatment patterns that may indicate treatment
      resistance or intolerance. We addressed these challenges by replicating active CE
      monitoring with sequential matched cohort analysis. RESULTS: Patients initiating
      new drugs were more likely to have used other drugs for the same indication in
      the past, but the majority of patients in all new drug cohorts were treatment
      naive (82.0% overall). Patients initiating rofecoxib had higher predicted
      baseline risk of gastrointestinal bleed than did patients initiating ns-NSAIDs.
      Patients initiating risedronate and alendronate had similar predicted baseline
      risks of fracture, while those initiating raloxifene and simvastatin + ezetimibe
      had lower risks of outcomes of interest relative to their comparators.
      Prospective monitoring yielded results consistent with expectation for each
      example. CONCLUSIONS: Many challenges to assessing the CE of new drugs are borne
      out in empirical data. Attention to these challenges can yield valid CE results.

PMID- 24041356
TI  - Priority preferences: "end of life" does not matter, but total life does.
AB  - There is increasing evidence that the social value of an incremental health gain
      depends on patient characteristics, such as their age and their prognosis. This
      article presents an analytical framework to illustrate how a disease splits our
      life expectancy into 1) past health (age), 2) prognosis untreated, 3) gain from
      treatment, and 4) incurable loss. A Norwegian population sample was asked to make
      pairwise choices and prioritize hypothetical patients who differed in terms of
      age (30, 50, and 70 years old), remaining lifetime without treatment (1, 3, and
      10 years), and increase in remaining lifetime with treatment (1 month, 3 months,
      1 year, and 3 years). Their preferences reveal strong support for the "fair
      innings" argument that total lifetime inequalities should be reduced. Differences
      in patients' remaining lifetime without treatment did not matter, implying little
      support for the "end-of-life" argument that a short life expectancy makes
      patients entitled to preferential treatment. 

PMID- 24041357
TI  - Early scientific advice obtained simultaneously from regulators and payers:
      findings from a pilot study in Australia.
AB  - OBJECTIVE: There is scope for better interaction between regulators, payers/HTA
      agencies, and medicines developers in their common objective of getting new
      medicines to patients. This paper reports on a tripartite early scientific advice
      pilot conducted by a pharmaceutical company (developer), the Therapeutic Goods
      Administration (TGA: regulator) and the Pharmaceutical Benefit Advisory Committee
      (PBAC) Secretariat (HTA agency) in Australia. The objective was to explore the
      practicality, feasibility, and sustainability of means of obtaining simultaneous
      scientific advice from both a regulatory and reimbursement perspective. METHODS:
      Advice was sought for two development compounds in different disease areas. The
      focus was on matters of common interest to the TGA and the PBAC (i.e. the
      clinical evidence). Briefing books were prepared by the developer and supplied
      eight weeks prior to the meeting and only verbal advice was provided. RESULTS:
      The pilot meeting took place in 2009. Each session lasted for approximately two
      hours and was structured around the questions in the briefing books. The
      representatives from the TGA and PBAC Secretariat provided well-informed,
      considered and careful advice for both compounds, which was predominantly
      actionable and practical. DISCUSSION: The sessions proved highly informative and
      permitted better alignment of the possible positioning of new medicines with the
      clinical evidence that regulators and HTA agencies might subsequently require for
      favorable assessment. The process provided early and clear signals to inform
      major development investments and the probability of successful market access. A
      number of challenges need to be addressed before tripartite scientific advice can
      be provided on continual basis.

PMID- 24041358
TI  - Performance of the UKPDS outcomes model for prediction of myocardial infarction
      and stroke in the ADDITION-Europe trial cohort.
AB  - OBJECTIVES: We assessed the performance of the UK Prospective Diabetes Study
      (UKPDS) outcomes model in predicting the risk of myocardial infarction (MI) and
      stroke in the Anglo-Danish-Dutch Study of Intensive Treatment in People with
      Screen Detected Diabetes in Primary Care (ADDITION-Europe) a trial cohort of
      patients with screen-detected type 2 diabetes from the United Kingdom, Denmark,
      and The Netherlands. METHODS: We estimated the 5-year accumulated risk of MI and
      stroke for 2899 screen-detected people with type 2 diabetes by using the UKPDS
      outcomes model (version 1.3). We compared the predicted and actual risks by
      country and by intervention group (routine care; intensive multifactorial
      treatment). We assessed discrimination and goodness of fit by using area under
      receiver operating characteristic curves and the Hosmer-Lemeshow chi-square test.
      Multiple imputations were used to overcome missing data. RESULTS: The UKPDS
      outcomes model overestimated the risk of MI and stroke. Mean predicted/actual
      ratios of 5-year accumulated risk were 2.31 for MI in the routine care group and
      3.97 in the intensive multifactorial treatment group and 1.59 and 1.48 for
      stroke, respectively. The differences in absolute risk between the intervention
      groups were underestimated for MI (observed vs. predicted: 0.0127 vs. 0.0009) and
      slightly overestimated for stroke (-0.0013 vs. -0.0004). The area under the
      receiver operating characteristic curve was 0.72 (95% confidence interval 0.66
      0.79) for MI and 0.70 (95% confidence interval 0.64-0.77) for stroke. The Hosmer
      Lemeshow test statistic was nonsignificant in all groups. The model performed
      better in absolute risk prediction in Denmark and the United Kingdom than in The
      Netherlands. CONCLUSIONS: The UKPDS outcomes model has moderate discriminatory
      ability in the ADDITION-Europe trial cohort but overestimated absolute risk. The
      model may need updating for cardiovascular disease risk prediction in
      contemporary diabetes populations where patients may be diagnosed earlier in the
      disease trajectory and in whom cardiovascular risk is therefore lower.

PMID- 24041359
TI  - Complete cytogenetic response and major molecular response as surrogate outcomes
      for overall survival in first-line treatment of chronic myelogenous leukemia: a
      case study for technology appraisal on the basis of surrogate outcomes evidence.
AB  - OBJECTIVES: In 2012, the National Institute for Health and Care Excellence
      assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment
      of chronic phase chronic myelogenous leukemia (CML). Licensing of these
      alternative treatments was based on randomized controlled trials assessing
      complete cytogenetic response (CCyR) and major molecular response (MMR) at 12
      months as primary end points. We use this case study to illustrate the validation
      of CCyR and MMR as surrogate outcomes for overall survival in CML and how this
      evidence was used to inform National Institute for Health and Care Excellence's
      recommendation on the public funding of these first-line treatments for CML.
      METHODS: We undertook a systematic review and meta-analysis to quantify the
      association between CCyR and MMR at 12 months and overall survival in patients
      with chronic phase CML. We estimated life expectancy by extrapolating long-term
      survival from the weighted overall survival stratified according to the
      achievement of CCyR and MMR. RESULTS: Five studies provided data on the
      observational association between CCyR or MMR and overall survival. Based on the
      pooled association between CCyR and MMR and overall survival, our modeling showed
      comparable predicted mean duration of survival (21-23 years) following first-line
      treatment with imatinib, dasatinib, or nilotinib. CONCLUSIONS: This case study
      illustrates the consideration of surrogate outcome evidence in health technology
      assessment. Although it is often recommended that the acceptance of surrogate
      outcomes be based on randomized controlled trial data demonstrating an
      association between the treatment effect on both the surrogate outcome and the
      final outcome, this case study shows that policymakers may be willing to accept a
      lower level of evidence (i.e., observational association).

PMID- 24041360
TI  - Health state valuation in low- and middle-income countries: a systematic review
      of the literature.
AB  - OBJECTIVE: Cost-utility analysis is widely used in high-income countries to
      inform decisions on efficient health care resource allocation. Cost-utility
      analysis uses the quality-adjusted life-year as the outcome measure of health.
      High-income countries have undertaken health state valuation (HSV) studies to
      determine country-specific utility weights to facilitate valuation of health
      related quality of life. Despite an evident need, however, the extent of HSVs in
      low- and middle-income countries (LMICs) is unclear. METHODS: The literature was
      searched systematically by using four databases and additional Web searches to
      identify HSV studies carried out in LMICs. The Preferred Reporting System for
      Systematic Reviews and Meta-Analysis (PRISMA) strategy was followed to ensure
      systematic selection of the articles. RESULTS: The review identified 17 HSV
      studies from LMICs. Twelve studies were undertaken in upper middle-income
      countries, while lower middle- and low-income countries contributed three and two
      studies, respectively. There were 7 generic HSV and 10 disease-specific HSV
      studies. The seven generic HSVs included five EuroQol five-dimensional
      questionnaire, one six-dimensional health state short form (derived from short
      form 36 health survey), and one Assessment of Quality of Life valuations. Time
      trade-off was the predominant valuation method used across all studies.
      CONCLUSIONS: This review found that health state valuations from LMICs are
      uncommon and utility weights are generally unavailable for these countries to
      carry out health economic evaluation. More HSV studies need to be undertaken in
      LMICs to facilitate efficient resource allocation in their respective health
      systems.

PMID- 24041361
TI  - The cloudy crystal ball of cost-effectiveness studies.
AB  - Despite the use of identical clinical trial data (Anastrazole, Tamoxifen, Alone
      or in Combination for the adjuvant treatment of postmenopausal women with
      localised hormone receptor-positive breast cancer data), not dependent on
      differences between countries, the outcome of 11 published cost-effectiveness
      analyses varied more than 20-fold. The observed wide variation in predicted life
      years gained (a parameter derived from clinical trial data) demonstrates that
      authors used substantially different methods for handling the same data. We
      therefore consider it to be of utmost importance to strive for standardization of
      and better guidance for disease-specific modeling in economic evaluations. 

PMID- 24041362
TI  - Cost-effectiveness of expanded newborn screening in Texas.

PMID- 24041363
TI  - Cost-effectiveness of expanded newborn screening in Texas-author response to
      letter to the editor.

PMID- 24041364
TI  - Improving model validation in health technology assessment: comments on
      guidelines of the ISPOR-SMDM modeling good research practices task force.

PMID- 24041365
TI  - ISPOR-SMDM task force's recommendations for good modeling practices-reply to
      letter to the editor by Corro Ramos.

PMID- 24041366
TI  - Altered chromatin condensation of heat-stressed spermatozoa perturbs the dynamics
      of DNA methylation reprogramming in the paternal genome after in vitro
      fertilisation in cattle.
AB  - Shortly after penetration of the oocyte, sperm DNA is actively demethylated,
      which is required for totipotent zygotic development. Aberrant DNA methylation is
      thought to be associated with altered chromatin condensation of spermatozoa. The
      objectives of this study were to investigate the dynamics of DNA methylation
      reprogramming in the paternal pronucleus and subsequent fertilisation potential
      of heat-stressed bull spermatozoa having altered chromatin condensation. Hence,
      bovine zygotes (n=1239) were collected at three different time points (12, 18 and
      24h post insemination, hpi), and stained with an antibody against 5
      methylcytosine. Fluorescence intensities of paternal and maternal pronuclei were
      measured by ImageJ. DNA methylation patterns in paternal pronuclei derived from
      heat-stressed spermatozoa did not differ between time points (P>0.05), whereas
      control zygotes clearly showed demethylation and de novo methylation at 18 and
      24hpi, respectively. Moreover, heat-stressed spermatozoa showed a highly reduced
      (P<0.01) fertilisation rate compared with non-heat-stressed or normal control
      spermatozoa (53.7% vs 70.2% or 81.5%, respectively). Our data show that the
      normal pattern of active DNA demethylation followed by de novo methylation in the
      paternal pronucleus is perturbed when oocytes are fertilised with heat-stressed
      spermatozoa, which may be responsible for decreased fertilisation potential. 

PMID- 24041367
TI  - Evaluating harm associated with anti-malarial drugs: a survey of methods used by
      clinical researchers to elicit, assess and record participant-reported adverse
      events and related data.
AB  - BACKGROUND: Participant reports of medical histories, adverse events (AE) and non
      study drugs are integral to evaluating harm in clinical research. However,
      interpreting or synthesizing results is complicated if studies use different
      methods for ascertaining and assessing these data. To explore how these data are
      obtained in malaria drug studies, a descriptive online survey of clinical
      researchers was conducted during 2012 and 2013. METHODS: The survey was
      advertised through e-mails, collaborators and at conferences. Questions aimed to
      capture the detail, rationale and application of methods used to obtain relevant
      data within various study designs and populations. Closed responses were analysed
      using proportions, open responses through identifying repeating ideas and
      underlying concepts. RESULTS: Of fifty-two respondents from 25 counties, 87%
      worked at an investigational site and 75% reported about an interventional study.
      Studies employed a range of methods to elicit, assess and record participant
      reported AEs and related data. Questioning about AEs in 31% of interventional
      studies was a combination of general (open questions about health) and structured
      (reference to specific health-related items), 26% used structured only and 18%
      general only. No observational studies used general questioning alone. A minority
      incorporated pictorial tools. Rationales for the questioning approach included:
      standardization of assessment or data capture, specificity or comprehensiveness
      of data sought, avoidance of suggestion, feasibility, and understanding
      participants' perceptions. Most respondents considered the approach they reported
      was optimal, though several reconsidered this. Four AE grading, and three
      causality assessment approaches were reported. Combining general and structured
      questions about non-study drug use were considered useful for revealing and
      identifying specific medicines, while pictures could enhance reports,
      particularly in areas of low literacy. CONCLUSIONS: It is critical to evaluate
      the safety of anti-malarial drugs being deployed in large, diverse populations.
      Many studies would be suitable for contributing to a larger body of evidence for
      answering questions on harm. However this survey showed that various methods are
      used to obtain relevant data, which could influence study results. As the best
      practices for obtaining such data are unclear, anti-malarial clinical researchers
      should work towards consensus about the selection and/or design of optimal
      methods.

PMID- 24041368
TI  - Biochemical determination of enzyme-bound metabolites: preferential accumulation
      of a programmed octaketide on the enediyne polyketide synthase CalE8.
AB  - Despite considerable interest in the enediyne family of antitumor antibiotics,
      assembly of their polyketide core structures in nature remains poorly understood.
      Discriminating methods to access enzyme-bound intermediates are critical for
      elucidating unresolved polyketide and nonribosomal peptide biosynthetic pathways.
      Here, we describe the development of broadly applicable techniques for the mild
      chemical release and analysis of intermediates bound to carrier proteins (CPs),
      providing access to these species even in sensitive systems. These techniques
      were applied to CalE8, the polyketide synthase (PKS) involved in calicheamicin
      biosynthesis, facilitating the unambiguous identification of enzyme-bound
      polyketides on an enediyne PKS. Moreover, these methods enabled the preparation
      of fully unloaded CalE8, providing a "clean slate" for reconstituted activity and
      allowing us to demonstrate the preferential accumulation of a PKS-bound
      octaketide with evidence of programmed processing control by CalE8. This
      intermediate, which has the expected chain length for enediyne core construction,
      could previously only be indirectly inferred. These studies prove that this
      polyketide is an authentic product of CalE8 and may be a key precursor to the
      enediyne core of calicheamicin, as it is the only programmed, enzyme-bound
      species observed for any enediyne system to date. Our experimental advances into
      a generally inaccessible system illustrate the utility of these techniques for
      investigating CP-based biosynthetic pathways. 

PMID- 24041369
TI  - Thermoacoustic chips with carbon nanotube thin yarn arrays.
AB  - Aligned carbon nanotube (CNT) films drawn from CNT arrays have shown the
      potential as thermoacoustic loudspeakers. CNT thermoacoustic chips with robust
      structures are proposed to promote the applications. The silicon-based chips can
      play sound and fascinating rhythms by feeding alternating currents and audio
      signal to the suspending CNT thin yarn arrays across grooves in them. In
      additional to the thin yarns, experiments further revealed more essential
      elements of the chips, the groove depth and the interdigital electrodes. The
      sound pressure depends on the depth of the grooves, and the thermal wavelength
      can be introduced to define the influence-free depth. The interdigital fingers
      can effectively reduce the driving voltage, making the chips safe and easy to
      use. The chips were successfully assembled into earphones and have been working
      stably for about one year. The thermoacoustic chips can find many applications in
      consumer electronics and possibly improve the audiovisual experience. 

PMID- 24041370
TI  - Food and Drug Administration: reclassification of blade form dental implants.

PMID- 24041371
TI  - Using anisotropy measurements from A-band photodissociation to interrogate the
      excited states of H2Se.
AB  - The A-band photodissociation of H2Se has been studied by measuring H-atom
      velocity-aligned Doppler spectroscopy (VADS) spectra at five wavelengths from 210
      to 266 nm. These spectra have been subsequently simulated by assigning cross
      sections and anisotropy beta values to the two SeH spin-orbit exit channels.
      While the SeH((2)Pi3/2) exit channel has a beta value close to -1 throughout the
      studied wavelength range, the spin-orbit excited SeH((2)Pi1/2) exit channel's
      beta value switches from near -1 to near +0.5 when the photolysis wavelength
      increases from 210 to 266 nm. These results have been examined in the light of
      available ab initio calculations. Throughout the studied wavelengths, the
      contribution from excitation to the 1(1)B1 state predominates and provides the
      source of the -1 beta value. In order to account for the +0.5 beta value, it is
      necessary to assume that the 2(1)A1 state as well as the 4A' and 5A' states (both
      originating from a (3)B1 state) also contribute at short wavelengths. More
      interestingly, at the longer wavelength end (266 nm), contribution of a +0.5 beta
      value from the 3A' state (originating from a (3)A2 state) exceeds the
      contribution of the -1 beta value for the SeH((2)Pi1/2) channel. 

PMID- 24041372
TI  - Invertebrate and avian predators as drivers of chemical defensive strategies in
      tenthredinid sawflies.
AB  - BACKGROUND: Many insects are chemically defended against predatory vertebrates
      and invertebrates. Nevertheless, our understanding of the evolution and diversity
      of insect defenses remains limited, since most studies have focused on visual
      signaling of defenses against birds, thereby implicitly underestimating the
      impact of insectivorous insects. In the larvae of sawflies in the family
      Tenthredinidae (Hymenoptera), which feed on various plants and show diverse
      lifestyles, two distinct defensive strategies are found: easy bleeding of
      deterrent hemolymph, and emission of volatiles by ventral glands. Here, we used
      phylogenetic information to identify phylogenetic correlations among various
      ecological and defensive traits in order to estimate the relative importance of
      avian versus invertebrate predation. RESULTS: The mapping of 12 ecological and
      defensive traits on phylogenetic trees inferred from DNA sequences reveals the
      discrete distribution of easy bleeding that occurs, among others, in the genus
      Athalia and the tribe Phymatocerini. By contrast, occurrence of ventral glands is
      restricted to the monophyletic subfamily Nematinae, which are never easy
      bleeders. Both strategies are especially effective towards insectivorous insects
      such as ants, while only Nematinae species are frequently brightly colored and
      truly gregarious. Among ten tests of phylogenetic correlation between traits,
      only a few are significant. None of these involves morphological traits enhancing
      visual signals, but easy bleeding is associated with the absence of defensive
      body movements and with toxins occurring in the host plant. Easy bleeding
      functions through a combination of attributes, which is corroborated by an
      independent contrasts test indicating a statistically significant negative
      correlation between species-level integument mechanical resistance and hemolymph
      feeding deterrence against ants. CONCLUSIONS: Our analyses evidence a repeated
      occurrence of easy bleeding, and no phylogenetic correlation including specific
      visual signals is significant. We conclude that the evolution of chemically-based
      defenses in tenthredinids may have been driven by invertebrate as much as by
      avian predation. The clear-cut visual signaling often encountered in the
      Nematinae would be linked to differential trends of habitat use by prey and
      predators. Further studies on (prey) insect groups should include visual signals
      and other traits, as well as several groups of natural enemies, to better
      interpret their relative significance and to refine our understanding of insect
      chemical defenses.

PMID- 24041373
TI  - A central storage facility to reduce pesticide suicides--a feasibility study from
      India.
AB  - BACKGROUND: Pesticide suicides are considered the single most important means of
      suicide worldwide. Centralized pesticide storage facilities have the possible
      advantage of delaying access to pesticides thereby reducing suicides. We
      undertook this study to examine the feasibility and acceptability of a
      centralized pesticide storage facility as a preventive intervention strategy in
      reducing pesticide suicides. METHODS: A community randomized controlled
      feasibility study using a mixed methods approach involving a household survey;
      focus group discussions (FGDs) and surveillance were undertaken. The study was
      carried out in a district in southern India. Eight villages that engaged in
      floriculture were identified. Using the lottery method two were randomized to be
      the intervention sites and two villages constituted the control site. Two
      centralized storage facilities were constructed with local involvement and
      lockable storage boxes were constructed. The household survey conducted at
      baseline and one and a half years later documented information on
      sociodemographic data, pesticide usage, storage and suicides. RESULTS: At
      baseline 4446 individuals (1097 households) in the intervention and 3307
      individuals (782 households) in the control sites were recruited while at follow
      up there were 4308 individuals (1063 households) in the intervention and 2673
      individuals (632 households) in the control sites. There were differences in
      baseline characteristics and imbalances in the prevalence of suicides between
      intervention and control sites as this was a small feasibility study.The results
      from the FGDs revealed that most participants found the storage facility to be
      both useful and acceptable. In addition to protecting against wastage, they felt
      that it had also helped prevent pesticide suicides as the pesticides stored here
      were not as easily and readily accessible. The primary analyses were done on an
      Intention to Treat basis. Following the intervention, the differences between
      sites in changes in combined, completed and attempted suicide rates per 100,000
      person-years were 295 (95% CI: 154.7, 434.8; p < 0.001) for pesticide suicide and
      339 (95% CI: 165.3, 513.2, p < 0.001) for suicide of all methods. CONCLUSIONS:
      Suicide by pesticides poisoning is a major public health problem and needs
      innovative interventions to address it. This study, the first of its kind in the
      world, examined the feasibility of a central storage facility as a means of
      limiting access to pesticides and, has provided preliminary results on its
      usefulness. These results need to be interpreted with caution in view of the
      imbalances between sites. The facility was found to be acceptable, thereby
      underscoring the need for larger studies for a longer duration. TRIAL
      REGISTRATION ISRCTN: ISRCTN04912407.

PMID- 24041374
TI  - The modulatory role of high fat feeding on gastrointestinal signals in obesity.
AB  - The gastrointestinal (GI) tract is a specialized sensory system that detects and
      responds to constant changes in nutrient- and bacterial-derived intestinal
      signals, thus contributing to controls of food intake. Chronic exposure to
      dietary fat causes morphological, physiological and metabolic changes leading to
      disruptions in the regulatory feeding pathways promoting more efficient fat
      absorption and utilization, blunted satiation signals and excess adiposity.
      Accumulating evidence demonstrates that impaired gastrointestinal signals
      following long-term high fat consumption are, at least partially, responsible for
      increased caloric intake. This review focuses on the role of dietary fat in
      modulating oral and post-oral chemosensory signaling elements responsible for
      lipid detection and responses, including changes in sensitivity to satiation
      signals, such as GLP-1, PYY and CCK and their impact on food intake and weight
      gain. Furthermore, the influence of the gut microbiota on mechanisms controlling
      energy regulation in the face of excessive fat exposure will be explored. The
      profound influence of dietary fats on altering complex regulatory feeding
      pathways can result in dysregulation of body weight and development of obesity,
      while restoration or manipulation of satiation signaling may prove an effective
      tool in prevention and treatment of obesity. 

PMID- 24041375
TI  - Comparison of risk assessment procedures used in OCRA and ULRA methods.
AB  - The aim of this study was to analyse the convergence of two methods by comparing
      exposure and the assessed risk of developing musculoskeletal disorders at 18
      repetitive task workstations. The already established occupational repetitive
      actions (OCRA) and the recently developed upper limb risk assessment (ULRA)
      produce correlated results (R = 0.84, p = 0.0001). A discussion of the factors
      that influence the values of the OCRA index and ULRA's repetitive task indicator
      shows that both similarities and differences in the results produced by the two
      methods can arise from the concepts that underlie them. The assessment procedure
      and mathematical calculations that the basic parameters are subjected to are
      crucial to the results of risk assessment. The way the basic parameters are
      defined influences the assessment of exposure and risk assessment to a lesser
      degree. The analysis also proved that not always do great differences in load
      indicator values result in differences in risk zones. PRACTITIONER SUMMARY: We
      focused on comparing methods that, even though based on different concepts, serve
      the same purpose. The results proved that different methods with different
      assumptions can produce similar assessment of upper limb load; sharp criteria in
      risk assessment are not the best solution.

PMID- 24041376
TI  - Calcium-alpha-L-guluronate complexes: Ca2+ binding modes from DFT-MD simulations.
AB  - The interactions of divalent calcium ions with a single alpha-L-guluronate anion
      and oligo(alpha-L-guluronate) chain have been studied in terms of the 'hybrid'
      molecular dynamics technique in which the selected parts of the system are
      treated with different level of theory (DFT-MD). The simulations were focused on
      obtaining the free energy profiles designed to clarify the possible calcium
      binding modes. In all considered cases, the calcium ion is coordinated by
      carboxyl oxygen atoms and water molecules exclusively. The results allowed for
      (i) determining the dentacy of calcium binding; (ii) estimating the calcium
      binding/unbinding-related free energy profiles; and (iii) positive verification
      of the previously [J. Comput. Chem. 2011, 32, 2988] proposed modification of the
      egg-box model describing the calcium alginate/guluronate structure. Additionally,
      the findings indicate that the polarization of the carboxyl group induced by the
      presence of Ca(2+) ion causes the increase of the free energy barrier separating
      the 'free' and 'bound' states of Ca(2+), in comparison to the classical
      biomolecular force fields (GROMOS/SPC and GLYCAM/TIP3P).

PMID- 24041377
TI  - Interpreting MYC and BCL2 in diffuse large B-cell lymphoma.

PMID- 24041378
TI  - A new feature in Leukemia & Lymphoma: "Emerging drug profile".

PMID- 24041379
TI  - Th17 cytokines in inflammatory bowel diseases: discerning the good from the bad.
AB  - T helper (Th) 17 cells are a branch of the CD4+ T cell compartment involved in
      host protection against bacterial and fungal infections as well as in
      orchestration of chronic inflammation and autoimmunity in many organs. Th17 cells
      produce interleukin (IL)-17A and variable amounts of IL-17F, IL-21, IL-22 and IL
      26, under the regulation of retinoic-acid-related orphan receptors (ROR)-gammat
      and ROR-alpha. Accumulating evidence supports the involvement of Th17 cells in
      the tissue-damaging immune response occurring in patients with Crohn's disease
      and patients with ulcerative colitis, the two major forms of inflammatory bowel
      disease (IBD) in human beings. However in the gut, Th17 cells can also have
      tissue-protective effects, mostly depending on their ability to enhance
      epithelial barrier function and counter-regulatory mechanisms. In this article,
      we summarize the available data on the dual role of Th17 cells in gut homeostasis
      and inflammation and discuss whether and how Th17 cytokine blockers can enter
      into the therapeutic armamentarium of IBD. 

PMID- 24041380
TI  - Can apical periodontitis modify systemic levels of inflammatory markers? A
      systematic review and meta-analysis.
AB  - INTRODUCTION: This systematic review and meta-analysis investigated evidence to
      support whether apical periodontitis (AP) can modify the systemic levels of
      inflammatory markers (IM) in humans. METHODS: The MEDLINE, Embase, Cochrane, and
      PubMed databases were searched between 1948 and 2012, with no language
      restriction. Additionally, the bibliography of all relevant articles and
      textbooks were manually searched. Based on inclusion and exclusion criteria, 2
      reviewers independently rated the quality of each study based on the Newcastle
      Ottawa Scale. The primary outcome variable for meta-analysis was determined by
      the serum levels of IMs in AP subjects versus healthy controls or in AP subjects
      before versus after treatment intervention. RESULTS: Among the 531 initially
      identified articles, 20 comprised the final analysis. Thirty-one different IMs
      were analyzed, with immunoglobulin (Ig) A, IgM, IgG, and C-reactive protein (CRP)
      being the most commonly investigated. CRP, interleukin (IL)-1, IL-2, IL-6,
      asymmetrical dimethylarginine, IgA, IgG, and IgM were shown to be increased in
      patients with AP compared with controls in most studies. Meta-analyses showed
      that serum levels of IgA (P = .001), IgG (P = .04), and IgM (P < .00001) were
      increased in humans with AP compared with healthy controls and serum levels of
      CRP, IgA, IgE, IgG, and IgM were not significantly different between patients
      with AP before and after treatment (P > .05). CONCLUSIONS: Available evidence is
      limited but consistent, suggesting that AP is associated with increased levels of
      CRP, IL-1, IL-2, IL-6, asymmetrical dimethylarginine, IgA, IgG, and IgM in
      humans. These findings suggest that AP may contribute to a systemic immune
      response not confined to the localized lesion, potentially leading to increased
      systemic inflammation.

PMID- 24041381
TI  - Radiographic healing after a root canal treatment performed in single-rooted
      teeth with and without ultrasonic activation of the irrigant: a randomized
      controlled trial.
AB  - INTRODUCTION: The aim of this study was to compare the outcome of a root canal
      treatment with and without additional ultrasonic activation of the irrigant.
      METHODS: Single-rooted teeth with radiographic evidence of periapical bone loss
      were randomly assigned to 2 treatment groups. In both groups syringe irrigation
      was performed, and in one group the irrigant was also activated by ultrasound.
      Ten to 19 months after treatment, the teeth were examined by using periapical
      radiography (PA) and cone-beam computed tomography (CBCT). Area and volume of the
      periapical lesions were measured, and the outcome was presented in 4 categories:
      absence, reduction or enlargement of the radiolucency, or uncertain. Lesions were
      classified as reduced or enlarged when the change in size of the radiolucency was
      20% or more. RESULTS: The recall rate was 82%, and 84 teeth were analyzed. CBCT
      detected significantly more post-treatment lesions than PA (P = .038), but the
      percentages of absence and reduction of the radiolucency together revealed by
      CBCT and PA were similar (P = .383). The CBCT results showed that absence of the
      radiolucency was observed in 16 of 84 teeth (19%) and reduction of the
      radiolucency in 61 of 84 teeth (72.6%), but there was no significant difference
      between the results of the 2 groups (P = .470). Absence and reduction of the
      radiolucency together were observed in the ultrasonic group in 39 of 41 teeth
      (95.1%) and in the syringe group in 38 of 43 teeth (88.4%). CONCLUSIONS: Root
      canal treatments with and without additional ultrasonic activation of the
      irrigant contributed equally to periapical healing.

PMID- 24041382
TI  - A survey of dentists' preferences for the treatment of teeth with apical
      periodontitis.
AB  - INTRODUCTION: This study surveyed the preferences of Ontario, Canada dentists for
      teeth with apical periodontitis when selecting between retention via root canal
      treatment (RCT) and extraction without replacement, or replacement with implant
      supported crowns (ISC), fixed, or removable partial prostheses. METHODS: A mail
      out survey (census of Ontario endodontists, periodontists, prosthodontists, and
      oral and maxillofacial surgeons; n = 498, 40% response rate) and a Web-based
      survey (sample of Ontario general dentists; n = 1983, 15% response rate) were
      conducted. Participants ranked their treatment preferences for 4 clinical
      scenarios: an anterior or posterior tooth, without or with previous RCT.
      Associations between treatment preferences and covariates were explored by using
      bivariate and logistic regression analyses (P <= .05). RESULTS: For all 4
      scenarios, the majority of participants preferred either RCT or ISC, whereas
      other treatment options were preferred by <= 3.1% of the participants in any
      professional registration category. A pattern of declining preference for RCT and
      increasing preference for ISC was noted across the scenarios, with significantly
      lower preference for RCT and higher preference for ISC associated with teeth
      needing repeated RCT compared with initial RCT (odds ratio [OR] = 3.3; confidence
      interval [CI], 2.5-4.4). Preferences were significantly lower for RCT and higher
      for ISC among general dentists (OR = 6.4; CI, 2.3-17.6), prosthodontists (OR =
      9.1; CI, 3.0-28.3), periodontists (OR = 18.3; CI, 6.4-51.6), and surgeons (OR =
      30.1; CI, 10.8-86.6) when compared with endodontists. CONCLUSIONS: More surveyed
      dentists preferred RCT than ISC for teeth with apical periodontitis requiring
      initial RCT than repeated RCT. The dentists' preferences were associated with
      their professional registration but not with other characteristics.

PMID- 24041383
TI  - High levels of CXC ligand 12/stromal cell-derived factor 1 in apical lesions of
      endodontic origin associated with mast cell infiltration.
AB  - INTRODUCTION: CXC ligand 12/stromal-derived factor-1 (CXCL12/SDF-1) is a
      pleiotropic chemokine that regulates the influx of a wide range of leukocytes.
      The aim of this study was to characterize CXCL12/SDF-1 in apical lesions (ALs) of
      endodontic origin, with special emphasis in associated immune cell populations.
      METHODS: In this case-control study, 29 individuals with chronic apical
      periodontitis and 21 healthy volunteers were enrolled. ALs and healthy
      periodontal ligament samples were obtained for tissue homogenization, immune
      Western blotting, and enzyme-linked immunosorbent assay to determine CXCL12/SDF-1
      forms and levels. Anatomopathologic diagnosis, immunostaining for CXCL12/SDF-1,
      CD117-CXCL12/SDF-1, and toluidine blue were also performed to identify tissue and
      cell localization. Finally, a set of tissue samples were digested and analyzed by
      flow cytometry to identify CXCL12/SDF-1 in different immune cell populations.
      Data were analyzed with Stata v11 and WinDi 2.9 software, and significance was
      considered if P < .05. RESULTS: CXCL12/SDF-1 was predominantly identified as
      monomers; levels of CXCL12/SDF-1 were significantly higher in ALs compared with
      controls, and it was primarily localized to inflammatory infiltrates. Expression
      of CXCL12/SDF-1 was colocalized to mast cells in tissue sections. Furthermore,
      CD117(+) mast cells were the second most frequent infiltrating cells and the main
      CXCL12/SDF-1 expressing cells, followed by CD4(+) lymphocytes,
      monocytes/macrophages, neutrophils, and dendritic cells. CONCLUSIONS: ALs of
      endodontic origin demonstrated higher levels of CXCL12/SDF-1 compared with
      controls. CXCL12/SDF-1 was identified in immune cell populations, whereas mast
      cells represented the major CXCL12/SDF-1 expressing cells, suggesting that this
      chemokine might play a central role in apical tissue destruction, most probably
      inducing persistent recruitment of immune cells, particularly of mast cells.

PMID- 24041384
TI  - Investigation of cultivable bacteria isolated from longstanding retreatment
      resistant lesions of teeth with apical periodontitis.
AB  - INTRODUCTION: The objective of this research was to investigate the presence of
      viable bacteria in tissue samples from persistent apical lesions and to correlate
      the microbiological findings with the histopathological diagnosis of the lesion.
      METHODS: Twenty persistent apical lesions associated with well-performed
      endodontic retreatment were collected. Tissue samples were processed through
      culture techniques including serial dilution, plating, aerobic and anaerobic
      incubation, and biochemical tests for microbial identification followed by
      histopathological diagnosis. RESULTS: Cysts were more frequently diagnosed
      (13/20). Strict anaerobic species predominated in both cysts (80.4% of the
      species detected) and granulomas (65% of the species detected). Viable gram
      positive bacteria were frequently recovered from apical lesions (cysts = 70.6%,
      granulomas = 84.4%). Gemella morbillorum and Propionibacterium acnes were the
      most frequently recovered species from cysts and granulomas, respectively. At
      least 1 gram-positive bacterial species was present in almost every sample (cysts
      = 12/13, granulomas = 7/7). No significant correlation was found between
      histologic findings and bacterial species. CONCLUSIONS: In conclusion, although
      cysts were more frequent than granulomas in cases of failure of endodontic
      retreatment, bacteria were isolated from both types of lesions, with a
      predominance of gram-positive species, suggesting that these species can survive
      outside the root canal and might be related to the persistence of the
      pathological process even after accurate endodontic retreatment.

PMID- 24041385
TI  - Area and 3-dimensional volumetric changes of periapical lesions after root canal
      treatments.
AB  - INTRODUCTION: This study compared the changes in size of periapical lesions after
      root canal treatment as revealed by periapical radiography (PA) and cone-beam
      computed tomography (CBCT) imaging using area and 3-dimensional volumetric
      measurements and assessed the outcome of the treatments based on these
      parameters. METHODS: Both PA and CBCT scans were taken preoperatively and at
      recall. In total, 50 teeth (71 roots) with evidence of periapical bone loss on
      both PA and CBCT images were endodontically treated and followed for 10-37
      months. The area and volume of periapical lesions were measured, and changes were
      presented in the following 4 categories: lesion undetected, lesion reduced in
      size, lesion unchanged, or lesion enlarged. The McNemar and chi-square tests were
      used to compare the lesion changes determined by CBCT imaging and PA. RESULTS:
      The 4-category diagnosis made using both methods were in agreement in 39 of 71
      (54.9%) roots, whereas disagreement was observed in 32 of 71 (45.1%) roots (P <
      .001). At recall, lesion was absent in 11 of 71 (15.5%) roots on CBCT scans and
      32 of 71 (45.1%) roots on PA (P < .001). When success was defined as the absence
      of a lesion or a reduction in size of a lesion, 55 (77.5%) roots on CBCT imaging
      showed success and 63 (88.7%) roots on PA (P = .073). CONCLUSIONS: Changes in
      lesion size after root canal treatment determined with 3-dimensional volumetric
      CBCT data and 2-dimensional PA data are different. The outcome of root canal
      treatments determined with PA could be untrue.

PMID- 24041386
TI  - Dynamics of bromodeoxyuridine label-retaining dental pulp cells during pulpal
      healing after cavity preparation in mice.
AB  - INTRODUCTION: This study aimed at clarifying the dynamics of bromodeoxyuridine
      (BrdU) label-retaining cells (LRCs) and their relationship to cell proliferation
      and apoptosis during pulpal healing after cavity preparation in mice. METHODS: A
      groove-shaped cavity was prepared on the mesial cervical surface of the upper
      first molars, and the samples were collected at intervals of 12 hours-14 days.
      The demineralized paraffin sections were processed for immunohistochemistry for
      BrdU, nestin, and Ki-67 and apoptosis assay using terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) and in
      situ hybridization for dentin sialophosphoprotein (Dspp). RESULTS: During hour 12
      day 1, odontoblasts and subodontoblastic cells beneath the affected dentin showed
      degenerative features and TUNEL-positive reactions, and the expressions of nestin
      and Dspp were lost in the damaged odontoblasts. TUNEL-positive reactions were
      observed even in the center of the pulp tissue, whereas dense and granular LRCs
      remained there. On days 2-3, Ki-67-positive cells were significantly increased in
      number in the center of mesial dental pulp. During days 3-5, granular and few
      dense LRCs were committed into some (not all) nestin-positive newly
      differentiated odontoblast-like cells, and these differentiated cells began to
      express nestin and Dspp. Until day 14, tertiary dentin formation occurred next to
      the preexisting dentin at the mesial pulp floor in addition to the mesial coronal
      pulp. CONCLUSIONS: These results suggest that odontoblasts and subodontoblastic
      cells degenerate after tooth drilling, and, subsequently, dental pulp
      stem/progenitor cells actively proliferate and differentiate into new odontoblast
      like cells.

PMID- 24041387
TI  - EphB-EphrinB interaction controls odontogenic/osteogenic differentiation with
      calcium hydroxide.
AB  - INTRODUCTION: Calcium hydroxide is used in direct pulp capping of uncontaminated
      exposed vital pulps caused by mechanical or traumatic injury. Calcium hydroxide
      creates a high alkaline pH environment and initiates a mineralized tissue
      formation in the pulp. The exact mechanism by which calcium hydroxide induces the
      reparative dentin formation is unknown. Because Eph receptors and ephrin ligands
      play a role in pulp stem cell migration and proliferation, our hypothesis is that
      calcium hydroxide-related odontogenic/osteogenic differentiation may be
      associated with Eph-ephrin interaction. The aim of this study was to investigate
      whether Eph-ephrin interaction regulates odontogenic/osteogenic differentiation
      with calcium hydroxide. METHODS: Primary pulp cells were harvested from the
      molars of C57BL/6 mice. The cells were treated with calcium hydroxide.
      Immunofluorescence was used to detect protein expression. A knockout of the
      ephrinB1 or EphB2 gene was performed with short hairpin RNAs. Cell migration,
      proliferation, and gene expression were then analyzed. RESULTS: Calcium hydroxide
      stimulated EphB2 gene expression but suppressed ephrinB1 gene expression at the
      proliferation stage. However, calcium hydroxide stimulated both ephrinB1 and
      EphB2 gene expression at the differentiation stage. In addition, EphB2 localized
      at ephrinB1-positive cells at the area of Dentin sialoprotein (DSP) staining,
      which increased with calcium hydroxide treatment. Knockdown of ephrinB1-EphB2
      significantly suppressed cell proliferation. Additionally, knockdown of the
      ephrinB1 gene caused cell migration, whereas a lack of the EphB2 gene suppressed
      calcium hydroxide-induced mineralization from primary pulp cells. CONCLUSIONS:
      EphrinB1-EphB2 interaction contributes to calcium hydroxide-induced
      odontogenic/osteogenic differentiation. This observation is the first finding of
      the mechanism of calcium hydroxide-induced odontogenic/osteogenic
      differentiation.

PMID- 24041388
TI  - Efficacy of peracetic acid in rapid disinfection of Resilon and gutta-percha
      cones compared with sodium hypochlorite, chlorhexidine, and povidone-iodine.
AB  - BACKGROUND: The aim of this investigation was to compare the effectiveness of 3%
      sodium hypochlorite (NaOCl), 2% chlorhexidine, 1% peracetic acid, and 10%
      povidone-iodine in the rapid disinfection of Resilon (Pentron Clinical
      Technologies, LLC, Wallingford, CT) and gutta-percha cones contaminated with
      Enterococcus faecalis and Bacillus subtilis. METHODS: Two hundred fifty-six
      samples consisting of 128 gutta-percha cones and 128 Resilon cones were used in
      this study. The materials were tested for disinfection according to the type of
      solution (3% NaOCl, 2% chlorhexidine, 1% peracetic acid, or 10% povidone-iodine),
      the time of exposure to each solution (1 or 5 minutes), and the type of
      microorganisms (E. faecalis or B. subtilis). Subsequent to the disinfection,
      samples were placed in test tubes containing 10 mL Mueller-Hinton broth and
      incubated at 37 degrees C for 7 days. All test tubes were observed at 24-hour
      intervals and visually checked for turbidity, signifying microbial growth.
      RESULTS: In this study, 1% peracetic acid showed the best results for both 1
      minute and 5 minutes of disinfection, 2% chlorhexidine showed the second best
      results although it was statistically at par with peracetic acid, and 3%
      hypochlorite ranked third in disinfection; this was statistically significant
      when compared with peracetic acid and chlorhexidine. Disinfection by povidone
      iodine was the least within all the groups for both contact times although
      disinfection for 5 minutes showed better results than disinfection for 1 minute
      for gutta-percha. CONCLUSIONS: The outcome of this study confirmed the efficacy
      of 1% peracetic acid and 2% chlorhexidine in the rapid disinfection of both
      Resilon and gutta-percha.

PMID- 24041389
TI  - Effect of F68, F127, and P85 pluronic block copolymers on odontogenic
      differentiation of human tooth germ stem cells.
AB  - INTRODUCTION: The major challenge in dental pulp engineering is to make a
      successful combination of stem cells and biomaterials with the aim of providing
      the differentiation of stem cells into odontogenic cell types. Among
      biomaterials, some types of pluronics have been reported to increase bone
      formation of stem cells. The effect of these pluronics on odontogenic
      differentiation has not been addressed yet. This study aimed to examine the
      effect of pluronics F68, F127, and P85 on odontogenic differentiation of stem
      cells derived from third molar tooth germs of young adults. METHODS: Human tooth
      germ stem cells (hTGSCs) were induced to differentiate into odontogenic cells in
      the presence of different concentrations of pluronics. Differentiation efficiency
      was assessed by quantitative real-time polymerase chain reaction for determining
      expression messenger RNA levels and by immunocytostaining for determining the
      protein expression of odontogenic markers (ie, dentin sialoprotein, dentin matrix
      protein 1, bone morphogenic protein 2, bone morphogenic protein 7) by measuring
      alkaline phosphatase enzyme activity and lastly by von Kossa staining for
      determining mineralization. RESULTS: The results revealed for the first time that
      F68 has a great potential to boost odontogenic differentiation of hTGSCs. P85 was
      found to reduce cell viability during differentiation. F127 was nontoxic to
      hTGSCs but did not have any effect on differentiation. CONCLUSIONS: The positive
      effect of F68 on odontogenic differentiation might enable more efficient pulp
      regeneration. Yet, the exact mechanism of how F68 alters the differentiation
      pattern of hTGSCs remains to be investigated in the future studies.

PMID- 24041390
TI  - Growth and differentiation factor-5 regulates the growth and differentiation of
      human dental pulp cells.
AB  - INTRODUCTION: Growth and differentiation factor-5 (GDF-5) is a multifunctional
      protein that regulates the development and repair in many tissues. The purpose of
      this study was to investigate whether GDF-5 may influence the proliferation,
      differentiation, and collagen turnover of human dental pulp cells. METHODS: Human
      dental pulp cells were treated with different concentrations of GDF-5 (0-500
      ng/mL). Morphology of pulp cells was observed under a microscope. Cell
      proliferation was evaluated by 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl
      tetrazolium bromide assay. Immunofluorescent assay was used to observe the
      percentages of cell mitosis. Collagen content was measured by Sircol collagen
      assay. Tissue inhibitor of metalloproteinase-1 level in the culture medium was
      measured with enzyme-linked immunosorbent assay and Western blotting. Cell
      differentiation was evaluated by alkaline phosphatase (ALP) staining and ALP
      enzyme activity assay. RESULTS: After exposure of dental pulp cells to various
      concentrations of GDF-5, cell number was up-regulated significantly in dose
      dependent manner. GDF-5 also stimulated mitosis of dental pulp cells as indicated
      by an increased percentage of binucleated cells from 28% to 35%-45%. GDF-5 did
      not affect the collagen content and tissue inhibitor of metalloproteinase-1 level
      of pulp cells. GDF-5 decreased the ALP activity of pulp cells as analyzed by ALP
      staining and enzyme activity assay, with 14%-44% of inhibition. CONCLUSIONS: GDF
      5 revealed mitogenic and proliferative activity to dental pulp cells. GDF-5
      showed inhibitory effect on ALP activity but little effect on the collagen
      turnover. These events are crucial in specific stages of dental pulp repair and
      regeneration. GDF-5 may be potentially used for tissue engineering of pulp-dentin
      complex.

PMID- 24041391
TI  - Apical extrusion of debris using self-adjusting file, reciprocating single-file,
      and 2 rotary instrumentation systems.
AB  - INTRODUCTION: The purpose of this study was to evaluate the weight of debris
      extruded apically from teeth using different in vitro preparation techniques.
      METHODS: Sixty-eight extracted human mandibular premolars with single canals and
      similar lengths were instrumented using ProTaper F2 (25, .08; Dentsply Maillefer,
      Ballaigues, Switzerland), the Self-Adjusting File (1.5-mm diameter; Re-Dent Nova,
      Ra'anana, Israel), Revo-S SU (25, .06; MicroMega, Besancon, France), or Reciproc
      (R25; VDW GmbH, Munich Germany). Debris extruded during instrumentation were
      collected into preweighed Eppendorf tubes. The Eppendorf tubes were then stored
      in an incubator at 70 degrees C for 5 days. The Eppendorf tubes were weighed to
      obtain the final weight of the Eppendorf tubes when the extruded debris were
      included. Three consecutive weights were obtained for each tube. RESULTS: There
      were no statistically significant differences among the groups (P = .218). The
      ProTaper group produced the highest mean extrusion value. The Reciproc produced
      less debris compared with all the other instruments (P > .05). CONCLUSIONS: All
      instrumentation techniques were associated with extruded debris.

PMID- 24041392
TI  - Physical properties of 5 root canal sealers.
AB  - INTRODUCTION: The aim of this study was to evaluate the pH change, viscosity and
      other physical properties of 2 novel root canal sealers (MTA Fillapex and
      Endosequence BC) in comparison with 2 epoxy resin-based sealers (AH Plus and
      ThermaSeal), a silicone-based sealer (GuttaFlow), and a zinc oxide-eugenol-based
      sealer (Pulp Canal Sealer). METHODS: ISO 6876/2001 specifications were followed.
      The pH change of freshly mixed and set sealers was evaluated during periods of 1
      day and 5 weeks, respectively. The viscosity was investigated at different
      injection rates (72, 10, and 5 mm/min) at room temperature by using a syringe
      based system that was based on the Instron 3360 series universal testing system.
      RESULTS: The flow, dimensional change, solubility, and film thickness of all the
      tested sealers were in agreement with ISO 6876/2001 recommendations. The MTA
      Fillapex sealer exhibited a higher flow than the Endosequence BC sealer (P <
      .05). The MTA Fillapex and Endosequence BC sealers showed the highest film
      thicknesses among the tested samples. The Endosequence BC sealer exhibited the
      highest value of solubility, which was in accordance with 3% mass fraction
      recommended by the ISO 6876/2001, and showed an acceptable dimensional change.
      The MTA Fillapex and Endosequence BC sealers presented an alkaline pH at all
      times. The pH of fresh samples of the AH Plus and ThermaSeal sealers was alkaline
      at first but decreased significantly after 24 hours. The viscosity of the tested
      sealers increased with the decreased injection rates. CONCLUSIONS: The tested
      sealers were pseudoplastic according to their viscosities as determined in this
      study. The MTA Fillapex and Endosequence BC sealers each possessed comparable
      flow and dimensional stability but higher film thickness and solubility than the
      other sealers tested.

PMID- 24041393
TI  - A simple 2-step silane treatment for improved bonding durability of resin cement
      to quartz fiber post.
AB  - INTRODUCTION: This study examined a clinically feasible protocol for improving
      hydrolytic stability using a 2-step silanization including a nonorganofunctional
      silane. METHODS: The surfaces of 24 D.T. Light-Posts (Bisco Inc, Schaumburg, IL)
      were polished and assigned to the following 4 groups: M: 1-step silanization with
      Monobond-S (MS) (Ivoclar Vivadent, Schaan, Liechtenstein); BM: 2-step
      silanization with 5% 1,2-bis(triethoxysilyl)ethane and then MS; and HM and HBM: 1
      step and 2-step silanization, respectively, after 24% H2O2 etching. Four resin
      composite cylinders (RelyX Unicem; 3M ESPE, St Paul, MN) were bonded on each
      surface according to a microshear testing protocol. All bonded samples were
      stored in water at 37 degrees C for 24 hours, and half of them were then
      thermocycled 5000 times before microshear testing (n = 12). The failure modes
      were evaluated under an optical and scanning electron microscope. Water contact
      angles were measured on the post surfaces before and after silanization to
      estimate surface hydrophobicity. The results were statistically analyzed using 2
      way analysis of variance and the Tukey test. RESULTS: The bond strengths for the
      BM and HBM groups were significantly higher than the M and HM groups at 5000
      thermocycles (P < .05), whereas no significant differences were found between the
      4 groups before thermocycling (P > .05). All debonded samples showed some
      fractured fibers. No significant difference in the hydrophobicity was found
      between the 1-step and 2-step silanized post surfaces (P > .05). CONCLUSIONS: The
      2-step 1,2-bis(triethoxysilyl)ethane/MS treatment has potential as a silanization
      procedure for enhancing the hydrolytic stability of the fiber post/resin
      composite interface.

PMID- 24041395
TI  - Effects of piezoelectric units on pacemaker function: an in vitro study.
AB  - INTRODUCTION: The use of piezoelectric units on patients with pacemakers is
      generally discouraged, although there is no empirical evidence of the effects of
      current piezoelectric units on pacemaker activity in vitro. METHODS: Four
      piezoelectric units (Piezosurgery3, Piezotome, Piezotome2, and Variosurg) and 2
      magnetostriction units (Piezotome and Piezotome2) were tested for electromagnetic
      interference (EMI) with the SENSIA SESR01 pacemaker from Medtronic. The
      pacemaker, with a single electrode, was immersed in a saline-solution bath and
      adjusted between 400 and 800 ohms to simulate the electrical resistance of the
      human body and to register and to produce electrographic recordings. The
      pacemaker was tested with each ultrasonic device to analyze the presence of EMI
      at different distances, with the ultrasound switched on, switched off, and during
      operation. If any of the devices produced interference, the characteristics of
      the interference were categorized. RESULTS: In the positive control (direct
      contact between either the electrode or the generator and the ultrasound device
      when this was switched on), the pacemaker detected electrical activity as false
      heart activity. When all the scenarios and distances had been covered, no EMI was
      produced by the ultrasound units. CONCLUSIONS: No EMI was detected during the
      testing of the piezoelectric or magnetostriction units in this in vitro model of
      pacemaker use.

PMID- 24041394
TI  - Is pulp regeneration necessary for root maturation?
AB  - INTRODUCTION: True regeneration of the dental pulp-dentin complex in immature
      teeth with necrotic pulps has not been shown histologically. It is not known to
      what extent this true tissue regeneration is necessary to achieve clinically
      acceptable outcomes. METHODS: This case report describes the treatment of a
      patient with an immature maxillary right central incisor with a history of impact
      trauma and enamel-dentin crown fracture. A diagnosis of pulp necrosis with acute
      apical abscess was established. A regenerative endodontic protocol that used a
      paste containing Augmentin for 5 weeks as an intracanal medicament was used.
      RESULTS: Follow-ups at 9, 12, 17, and 31 months revealed complete osseous healing
      of the periapical lesion and formation of the root apex, but without increase in
      root length. Clinically, the tooth was functional, asymptomatic, and
      nonresponsive to pulp vitality tests. The crown discolored over time. On
      reentering the root canal, no tissues were observed under magnification inside
      the root canal space. The root canal treatment was completed with mineral
      trioxide aggregate obturation. CONCLUSIONS: Augmentin might be an acceptable
      choice for root canal disinfection in regenerative endodontic procedures. The
      protocol for regenerative endodontic treatment is not predictable for pulp-dentin
      regeneration. Formation of the root apex is possible without pulp regeneration.

PMID- 24041396
TI  - Comparison of the time required to create secondary fracture of separated file
      fragments by using ultrasonic vibration under various canal conditions.
AB  - INTRODUCTION: Nickel-titanium files often separate because of mechanical fatigue.
      The purpose of this study was to determine safe preparation techniques for
      separated file removal by using ultrasonics. METHODS: Fifty nickel-titanium file
      fragments were divided into 5 groups. An ultrasonic tip was activated on a file
      fragment positioned between dentin blocks simulating several canal conditions:
      Group 1 consisted of the fragment protruding from a pair of straight dentin
      blocks. For group 2, the fragment was also positioned between 2 straight dentin
      blocks except one block was positioned 1 mm more apically than the other block,
      simulating a troughed area that is often created during file removal attempts.
      For groups 3-5, the fragment was positioned similarly as group 2 but between
      blocks with 30 degrees , 45 degrees , and 60 degrees  curvatures, respectively.
      The time it took for secondary fracture to occur was recorded, and the data were
      statistically analyzed. RESULTS: Fragments with dentin wall supporting on the
      opposite side of ultrasonic activation site resisted fracture significantly
      longer than those without it. Fragments in 30 degrees  and 45 degrees  curved
      blocks took significantly longer to fracture than the other groups (Fisher
      protected least significant difference, P < .05). CONCLUSIONS: Secondary fracture
      of separated files appeared to be reduced when the ultrasonic tip was applied to
      the inner curvature of the canal.

PMID- 24041397
TI  - Parafoveal preprocessing in reading revisited: evidence from a novel preview
      manipulation.
AB  - The study investigated parafoveal preprocessing by the means of the classical
      invisible boundary paradigm and a novel manipulation of the parafoveal previews
      (i.e., visual degradation). Eye movements were investigated on 5-letter target
      words with constraining (i.e., highly informative) initial letters or similarly
      constraining final letters. Visual degradation was administered to all, no, the
      initial, or the final 2 letters of the parafoveal preview of the target words.
      Critically, the manipulation of the parafoveal previews did not interfere with
      foveal processing. Thus, we had a proper baseline to which we could relate our
      main findings, which were as follows: First, the valid (i.e., nondegraded)
      preview of the target words' final letters led to shorter fixation times compared
      to the baseline condition (i.e., the degradation of all letters). Second, this
      preview benefit for the final letters was comparable to the benefit of previewing
      the initial letters. Third, the preview of a constraining initial letter
      sequence, however, yielded a larger preview benefit than the preview of an
      unconstraining initial letter sequence. The latter finding indicates that
      preprocessing constraining initial letters is particularly conducive to foveal
      word recognition.

PMID- 24041398
TI  - Impact of the simulated diagenesis on sorption of naphthalene and 1-naphthol by
      soil organic matter and its precursors.
AB  - Soil organic matter (SOM) in a peat soil, humic acid, and humin and their
      precursors (i.e., cellulose and lignin) were treated at high temperature (250 and
      400  degrees C) with high pressure in a sealed platinum reaction kittle to
      simulate the influence of diagenesis on their composition and structure, and
      impact of the simulated diagenesis on sorption behaviors of hydrophobic organic
      compounds (HOCs) (i.e., naphthalene and 1-naphthol) by these samples was
      investigated. High temperature and pressure treatment greatly influenced chemical
      composition and physical properties of the original samples and their sorption
      for both naphthalene and 1-naphthol. Sorption of naphthalene by all samples was
      jointly regulated by hydrophobic and pi-pi interactions with their alkyl and
      aromatic carbon moieties, which was derived from the positive correlation between
      total hydrophobic carbon content of all sorbents and their organic carbon content
      normalized sorption coefficients (Koc) for this compound (p = 0.075). However,
      sorption of 1-naphthol by the tested sorbents was governed by hydrogen bonding
      with their O-containing polar functionalities, as derived from the positive
      correlation between Koc values of 1-Naph and their polarity index ((O+N)/C).
      Difference in sorption mechanisms of naphthalene and 1-naphthol by the original
      and treated samples noted the great influence of chemical composition of sorbates
      on their interaction and essential roles of specific interactions (e.g., hydrogen
      bonding) in sorption of polar compound (i.e., 1-naphthol) to these sorbents.
      Surface area (SA) and porosity data of sorbents obtained from N2 sorption
      desorption isotherms at 77 K showed that new SA and pores were created during the
      diagenetic process of all original samples, which provided substantial sorption
      sites and thus enhanced sorption of naphthalene and 1-naphthol. Among all tested
      samples, physicochemical properties of cellulose were most strongly affected by
      the simulated diagenetic process, and impact of such a process on its sorption
      intensity for the tested compounds was the most significant. The characterization
      data of the treated sorbents showed that the high temperature and pressure
      treatment similarly simulated the naturally occurring diagenesis of SOMs and
      their precursors, which is a first attempt. These findings are valuable for
      better understanding of the sorption behaviors of HOCs to SOM and its precursors
      as affected by diagenesis, which in turn is critical for elucidating the
      transport and fate of HOCs in the environment. 

PMID- 24041399
TI  - Kinetics of laterally nanostructured vesicle formation by self-assembly of
      miktoarm star terpolymers in aqueous solution.
AB  - Dissipative particle dynamics (DPD) simulation was used to study the self
      assembly of laterally nanostructured vesicles in aqueous solution from MU
      [poly(ethylethylene)]-[poly(ethylene oxide)][poly(perfluoropropylene oxide)] (MU
      EOF) star terpolymers. The simulated results show that the laterally
      nanostructured vesicle forms when the length of the hydrophilic O blocks are
      relatively short. In the lateral nanostructure, the hexagonally packed domains
      formed by the hydrophobic F blocks are immersed in a two-dimensional hydrophobic
      E block matrix. The formation conditions and microstructure of the vesicles in
      our simulation agree with the reported experimental results from the literature.
      The complicated formation pathway of laterally nanostructured vesicles follows
      three stages: (1) combination of spherical and short cylindrical raspberry-like
      micelles into an intermediate polygonal sheet; (2) the intermediate polygonal
      sheet grows to form a larger polygonal sheet with a tail; (3) the large polygonal
      sheet with a tail eventually folds and forms a vesicle. 

PMID- 24041400
TI  - Rhodium catalyzed cyanation of chelation assisted C-H bonds.
AB  - A rhodium-catalyzed cyanation of chelation assisted C-H bonds is described
      employing N-cyano-N-phenyl-p-methylbenzenesulfonamide as an efficient cyanating
      reagent. The present method allowed the synthesis of various benzonitirle
      derivatives in good to excellent yield. A number of chelating groups are also
      effective in the present cyanation of C-H bonds. In addition, the developed
      methodology was applied in the formal synthesis of the isoquinoline alkaloid,
      menisporphine. 

PMID- 24041401
TI  - Robust fault detection for switched positive linear systems with time-varying
      delays.
AB  - This paper investigates the problem of robust fault detection for a class of
      switched positive linear systems with time-varying delays. The fault detection
      filter is used as the residual generator, in which the filter parameters are
      dependent on the system mode. Attention is focused on designing the positive
      filter such that, for model uncertainties, unknown inputs and the control inputs,
      the error between the residual and fault is minimized. The problem of robust
      fault detection is converted into a positive L1 filtering problem. Subsequently,
      by constructing an appropriate multiple co-positive type Lyapunov-Krasovskii
      functional, as well as using the average dwell time approach, sufficient
      conditions for the solvability of this problem are established in terms of linear
      matrix inequalities (LMIs). Two illustrative examples are provided to show the
      effectiveness and applicability of the proposed results. 

PMID- 24041402
TI  - Optimised sensor selection for control and fault tolerance of electromagnetic
      suspension systems: a robust loop shaping approach.
AB  - This paper presents a systematic design framework for selecting the sensors in an
      optimised manner, simultaneously satisfying a set of given complex system control
      requirements, i.e. optimum and robust performance as well as fault tolerant
      control for high integrity systems. It is worth noting that optimum sensor
      selection in control system design is often a non-trivial task. Among all
      candidate sensor sets, the algorithm explores and separately optimises system
      performance with all the feasible sensor sets in order to identify fallback
      options under single or multiple sensor faults. The proposed approach combines
      modern robust control design, fault tolerant control, multiobjective optimisation
      and Monte Carlo techniques. Without loss of generality, it's efficacy is tested
      on an electromagnetic suspension system via appropriate realistic simulations. 

PMID- 24041403
TI  - Metal speciation in health and medicine represented by iron and vanadium.
AB  - The influence of metals in biology has become more and more apparent within the
      past century. Metal ions perform essential roles as critical scaffolds for
      structure and as catalysts in reactions. Speciation is a key concept that assists
      researchers in investigating processes that involve metal ions. However,
      translation of the essential area across scientific fields has been plagued by
      language discrepancies. To rectify this, the IUPAC Commission provided a
      framework in which speciation is defined as the distribution of species. Despite
      these attempts, contributions from inorganic chemists to the area of speciation
      have not fully materialized in part because the past decade's contributions
      focused on technological advances, which are not yet to the stage of measuring
      speciation distribution in biological solutions. In the following, we describe
      how speciation influences the area of metals in medicine and how speciation
      distribution has been characterized so far. We provide two case studies as an
      illustration, namely, vanadium and iron. Vanadium both has therapeutic importance
      and is known as a cofactor for metalloenzymes. In addition to being a cation,
      vanadium(V) has analogy with phosphorus and as such is a potent inhibitor for
      phosphorylases. Because speciation can change the metal's existence in cationic
      or anionic forms, speciation has profound effects on biological systems. We also
      highlight how speciation impacts iron metabolism, focusing on the rather low
      abundance of biologically relevant iron cation that actually exists in biological
      fluids. fluids. Furthermore, we point to recent investigations into the mechanism
      of Fenton chemistry, and that the emerging results show pH dependence. The
      studies suggest formation of Fe(IV)-intermediates and that the generally accepted
      mechanism may only apply at low pH. With broader recognition toward biological
      speciation, we are confident that future investigations on metal-based systems
      will progress faster and with significant results. Studying metal complexes to
      explore the properties of a potential "active species" and further uncovering the
      details associated with their specific composition and geometry are likely to be
      important to the action. 

PMID- 24041404
TI  - Surface-initiated atom transfer radical polymerization-induced transformation of
      selenium nanowires into copper selenide@polystyrene core-shell nanowires.
AB  - This Article reports the first preparation of cuprous and cupric selenide
      nanowires coated with a ~5 nm thick sheath of polystyrene (copper
      selenide@polystyrene). These hybrid nanostructures are prepared by the
      transformation of selenium nanowires in a one-pot reaction, which is performed
      under ambient conditions. The composition, purity, and crystallinity of the
      copper selenide@polystyrene products were assessed by scanning transmission
      electron microscopy, electron energy-loss spectroscopy, X-ray powder diffraction,
      and X-ray photoelectron spectroscopy techniques. We determined that the single
      crystalline selenium nanowires are converted into polycrystalline copper
      selenide@polystyrene nanowires containing both cuprous selenide and cupric
      selenide. The product is purified through the selective removal of residual, non
      transformed selenium nanowires by performing thermal evaporation below the
      decomposition temperature of these copper selenides. Powder X-ray diffraction of
      the purified copper selenide nanowires@polystyrene identified the presence of
      hexagonal, cubic, and orthorhombic phases of copper selenide. These purified
      cuprous and cupric selenide@polystyrene nanowires have an indirect bandgap of
      1.44 eV, as determined by UV-vis absorption spectroscopy. This new synthesis of
      polymer-encapsulated nanoscale materials may provide a method for preparing other
      complex hybrid nanostructures. 

PMID- 24041405
TI  - Lethal cardiotoxicity, steatohepatitis, chronic pancreatitis, and acute enteritis
      induced by capecitabine and oxaliplatin in a 36-year-old woman.
AB  - A 36-year-old female was hospitalized with symptoms suggesting intestinal
      occlusion. She was diagnosed with adenocarcinoma of the ampulla of Vater (pT4N0
      stage) and underwent cephalic duodenopancreatectomy 8 months ago. Five cycles of
      postoperative chemotherapy were administrated using capecitabine and oxaliplatin
      (CAPOX or XELOX), the last one being completed 1 month ago. During the present
      hospitalization, because of normal computed tomography and ultrasound abdominal
      examination, rehydration and antibiotherapy were administrated. However, 4 days
      after hospital admission, the patient died. At autopsy and histological
      examination, we found a severe myocardial sclerosis with large scarring areas,
      severe steatohepatitis, chronic pancreatitis with large fibrotic areas, and acute
      enteritis. Alcohol consumption was denied. The patient died due to associated
      heart, liver and pancreatic failure. This multiorgan toxicity and death following
      CAPOX regimen had not yet been reported in the literature. VIRTUAL SLIDES: The
      virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/6472150549833105.

PMID- 24041407
TI  - Journal of Child and Adolescent Psychopharmacology. From the Editor-in-Chief's
      desk.

PMID- 24041406
TI  - Cellular and humoral immune responses against the Plasmodium vivax MSP-119
      malaria vaccine candidate in individuals living in an endemic area in north
      eastern Amazon region of Brazil.
AB  - BACKGROUND: Plasmodium vivax merozoite surface protein-1 (MSP-1) is an antigen
      considered to be one of the leading malaria vaccine candidates. PvMSP-1 is highly
      immunogenic and evidences suggest that it is target for protective immunity
      against asexual blood stages of malaria parasites. Thus, this study aims to
      evaluate the acquired cellular and antibody immune responses against PvMSP-1 in
      individuals naturally exposed to malaria infections in a malaria-endemic area in
      the north-eastern Amazon region of Brazil. METHODS: The study was carried out in
      Paragominas, Para State, in the Brazilian Amazon. Blood samples were collected
      from 35 individuals with uncomplicated malaria. Peripheral blood mononuclear
      cells were isolated and the cellular proliferation and activation was analysed in
      presence of 19 kDa fragment of MSP-1 (PvMSP-119) and Plasmodium falciparum PSS1
      crude antigen. Antibodies IgE, IgM, IgG and IgG subclass and the levels of TNF,
      IFN-gamma and IL-10 were measured by enzyme-linked immunosorbent assay. RESULTS:
      The prevalence of activated CD4+ was greater than CD8+ T cells, in both ex-vivo
      and in 96 h culture in presence of PvMSP-119 and PSS1 antigen. A low
      proliferative response against PvMSP-119 and PSS1 crude antigen after 96 h
      culture was observed. High plasmatic levels of IFN-gamma and IL-10 as well as
      lower TNF levels were also detected in malaria patients. However, in the 96 h
      supernatant culture, the dynamics of cytokine responses differed from those
      depicted on plasma assays; in presence of PvMSP-119 stimulus, higher levels of
      TNF were noted in supernatant 96 h culture of malaria patient's cells while low
      levels of IFN-gamma and IL-10 were verified. High frequency of malaria patients
      presenting antibodies against PvMSP-119 was evidenced, regardless class or IgG
      subclass.PvMSP-119-induced antibodies were predominantly on non-cytophilic
      subclasses. CONCLUSIONS: The results presented here shows that PvMSP-119 was able
      to induce a high cellular activation, leading to production of TNF and emphasizes
      the high immunogenicity of PvMSP-119 in naturally exposed individuals and,
      therefore, its potential as a malaria vaccine candidate.

PMID- 24041408
TI  - Escitalopram in the treatment of adolescent depression: a randomized, double
      blind, placebo-controlled extension trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the extended efficacy,
      safety, and tolerability of escitalopram relative to placebo in adolescents with
      major depressive disorder (MDD). METHODS: Adolescents (12-17 years) who completed
      an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in
      study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week,
      multisite extension trial; patients maintained the same lead-in randomization
      (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo)
      during the extension. The primary efficacy was Children's Depression Rating Scale
      Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8
      week lead-in study plus 16-week extension); the secondary efficacy was Clinical
      Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses
      used the last observation carried forward (LOCF) approach; sensitivity analyses
      used observed cases (OC) and mixed-effects model for repeated measures (MMRM).
      Safety was evaluated via adverse event (AE) reports and the clinician-rated
      Columbia-Suicide Severity Rating Scale (C-SSRS). RESULTS: Following lead-in, 165
      patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40
      (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R
      total score improvement was significantly greater for escitalopram than for
      placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R >= 40% reduction
      from baseline [adjusted and unadjusted] and CGI-I <= 2) were significantly higher
      for escitalopram than for placebo (LOCF); remission rates (CDRS-R <= 28) were
      50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not
      significantly different between groups. The most frequent escitalopram AEs (>= 5%
      and more frequent than placebo) were headache, nausea, insomnia, vomiting,
      influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were
      mild/moderate and not related to the study drug. AEs suggestive of self-harm
      occurred in 5.7% and 7.1% of placebo and escitalopram patients. Occurrence of
      suicidal behavior and/or suicidal ideation assessed by C-SSRS was 10.9% (14/128)
      for placebo and 14.5% (19/131) for escitalopram. CONCLUSIONS: Extended use of
      escitalopram was generally safe and resulted in modest improvement in efficacy in
      adolescents with MDD.

PMID- 24041409
TI  - A rare case of anti-N-methyl-D-aspartate receptor encephalitis in an adolescent.

PMID- 24041410
TI  - Calcium-dependent regulation of genes for plant nodulation in Rhizobium
      leguminosarum detected by iTRAQ quantitative proteomic analysis.
AB  - Rhizobia, the nitrogen-fixing bacterial symbionts of legumes, represent an
      agricultural application of primary relevance and a model of plant-microbe
      molecular dialogues. We recently described rhizobium proteome alterations induced
      by plant flavonoids using iTRAQ. Herein, we further extend that experimentation,
      proving that the transient elevation in cytosolic calcium is a key signaling
      event necessary for the expression of the nodulation (nod) genes. Ca(2+)
      involvement in nodulation is a novel issue that we recently flagged with genetic
      and physiological approaches and that hereby we demonstrate also by proteomics.
      Exploiting the multiple combinations of 4-plex iTRAQ, we analyzed Rhizobium
      leguminosarum cultures grown with or without the nod gene-inducing plant
      flavonoid naringenin and in the presence or absence of the extracellular Ca(2+)
      chelator EGTA. We quantified over a thousand proteins, 189 of which significantly
      altered upon naringenin and/or EGTA stimulation. The expression of NodA, highly
      induced by naringenin, is strongly reduced when calcium availability is limited
      by EGTA. This confirms, from a proteomic perspective, that a Ca(2+) influx is a
      necessary early step in flavonoid-mediated legume nodulation by rhizobia. We also
      observed other proteins affected by the different treatments, whose identities
      and roles in nodulation and rhizobium physiology are likewise discussed. 

PMID- 24041412
TI  - Effects of desialylation on human alpha1-acid glycoprotein-ligand interactions.
AB  - Human alpha1-acid glycoprotein (AGP), an acute-phase glycoprotein, exists
      predominantly in blood. With its ability to bind basic, lipophilic, and acidic
      drugs, AGP has served as a drug carrier. It has been shown that the carbohydrate
      composition of AGP changes in response to tissue injury, inflammation, or
      infection and can have a great impact on AGP's drug binding activities. The
      molecular-level details of the effects of desialylation on the AGP conformation
      and AGP-ligand interactions, however, are unknown. Here we report the use of
      hydrogen-deuterium exchange coupled with mass spectrometry (HDX-MS) to reveal the
      changes in AGP conformational dynamics induced by the removal of terminal sialic
      acid. HDX-MS also reveals the changes in the conformational dynamics of
      sialylated and unsialylated AGP upon formation of complexes of holo-AGP with
      progesterone or propranolol. Our HDX-MS results demonstrate that desialylation
      stabilizes two loop regions that are exterior to the beta-sheet barrel in AGP,
      and this stabilization minimizes the conformational changes of AGP upon binding
      with progesterone or propranolol. 

PMID- 24041411
TI  - The unique evolution of the programmed cell death 4 protein in plants.
AB  - BACKGROUND: The programmed cell death 4 (PDCD4) protein is induced in animals
      during apoptosis and functions to inhibit translation and tumor promoter-induced
      neoplastic transformation. PDCD4 is composed of two MA3 domains that share
      similarity with the single MA3 domain present in the eukaryotic translation
      initiation factor (eIF) 4G, which serves as a scaffold protein to assemble
      several initiation factors needed for the recruitment of the 40S ribosomal
      subunit to an mRNA. Although eIF4A is an ATP-dependent RNA helicase that binds
      the MA3 domain of eIF4G to promote translation initiation, binding of eIF4A to
      the MA3 domains of PDCD4 inhibits protein synthesis. Genes encoding PDCD4 are
      present in many lower eukaryotes and in plants, but PDCD4 in higher plants is
      unique in that it contains four MA3 domains and has been implicated in ethylene
      signaling and abiotic stress responses. Here, we examine the evolution of PDCD4
      in plants. RESULTS: In older algal lineages, PDCD4 contains two MA3 domains
      similar to the homolog in animals. By the appearance of early land plants,
      however, PDCD4 is composed of four MA3 domains which likely is the result of a
      duplication of the two MA3 domain form of the protein. Evidence from fresh water
      algae, from which land plants evolved, suggests that the duplication event
      occurred prior to the colonization of land. PDCD4 in more recently evolved
      chlorophytes also contains four MA3 domains but this may have resulted from an
      independent duplication event. Expansion and divergence of the PDCD4 gene family
      occurred during land plant evolution with the appearance of a distinct gene
      member following the evolution of basal angiosperms. CONCLUSIONS: The appearance
      of a unique form of PDCD4 in plants correlates with the appearance of components
      of the ethylene signaling pathway, suggesting that it may represent the
      adaptation of an existing protein involved in programmed cell death to one that
      functions in abiotic stress responses through hormone signaling.

PMID- 24041413
TI  - Behavioural response of grazing lambs to changes associated with feeding and
      separation from their mothers at weaning.
AB  - This study aimed to determine which behaviours were provoked in lambs in response
      to the separation from their dams or to the changes associated with feeding and
      separation from adults at weaning. Fourteen lambs were separated from their dams
      at 24-36 h after birth and artificially reared (AR) in presence of four adult
      ewes, while another 13 lambs remained with their dams from birth (DR). At 75 days
      of age on average (day 0) DR lambs were separated from their dams and AR lambs no
      longer received sheep's milk and were separated from adults. Behaviours were
      recorded every 10 min (6h per day) from day -3 to day 4. We observed an increase
      (p<0.05) in pacing behaviour, as well as in the frequency in which lambs were
      observed vocalizing, walking and staying under shade, and a decrease (p<0.05) in
      the frequency of grazing in the DR group in comparison to AR at weaning, but
      there were no differences in body weight gain from day -4 to day 5 after weaning.
      Additionally, we observed a decrease in the frequency in which lambs were
      observed standing and grazing (p<0.05), and an increase in vocalizing and staying
      under shade (p<0.05) in group AR at weaning in comparison to the previous days.
      Therefore, it was concluded that although some specific behaviours as pacing or
      vocalizing were clearly related with the separation from the mother at weaning,
      the change of food and separation from adults must be also considered as an
      important stressor in grazing lambs at weaning. In addition, the provision of
      shade when grazing is also important for lambs at the time of weaning.

PMID- 24041414
TI  - Coupling of transcriptional response to oxidative stress and secondary metabolism
      regulation in filamentous fungi.
AB  - To survive sudden and potentially lethal changes in their environment,
      filamentous fungi must sense and respond to a vast array of stresses, including
      oxidative stresses. The generation of reactive oxygen species, or ROS, is an
      inevitable aspect of existence under aerobic conditions. In addition, in the case
      of fungi with pathogenic lifestyles, ROS are produced by the infected hosts and
      serve as defense weapons via direct toxicity, as well as effectors in fungal cell
      death mechanisms. Filamentous fungi have thus developed complex and sophisticated
      responses to evade oxidative killing. Several steps are determinant in these
      responses, including the activation of transcriptional regulators involved in the
      control of the antioxidant machinery. Gathering and integrating the most recent
      advances in knowledge of oxidative stress responses in fungi are the main
      objectives of this review. Most of the knowledge coming from two models, the
      yeast Saccharomyces cerevisiae and fungi of the genus Aspergillus, is summarized.
      Nonetheless, recent information on various other fungi is delivered when
      available. Finally, special attention is given on the potential link between the
      functional interaction between oxidative stress and secondary metabolism that has
      been suggested in recent reports, including the production of mycotoxins. 

PMID- 24041415
TI  - [Why a monograph on hand injuries in children?].

PMID- 24041417
TI  - Side chain flexibility in perfluorosulfonic acid ionomers: an ab initio study.
AB  - Side chain flexibility in perfluorosulfonic acid (PFSA) ionomers has been
      explored through ab initio electronic structure calculations. Three different
      PFSA side chain fragments were considered with a CF3CFCF3 backbone
      representation: Nafion (-OCF2CF(CF3)O(CF2)2SO3H), Aquivion or the short side
      chain (SSC) (-O(CF2)2SO3H), and the 3M PFSA (-O(CF2)4SO3H). Rotational potential
      energy surfaces for each bond along the length of the side chains were obtained
      using density functional theory with the B3LYP and the dispersion-corrected B97D
      functionals with and without the inclusion of a solvation model. Solvent effects
      were found to have minimal effect on bond rotations close to the
      tetrafluoroethylene backbone but had greater impact near the terminal sulfonic
      acid group. The carbon-sulfur bond was found to be the most flexible portion of
      the side chain in each of the fragments which was further enhanced with the
      inclusion of the solvent. Complete rotation about either the O-CF2 or CF-O bond
      in the Nafion side chain resulted in fairly high energetic barriers, but
      significant portions of these rotational surfaces had energetic penalties less
      than 1.5 kcal/mol indicating substantial conformational freedom. Fully extended
      and folded conformations of the Nafion side chain exhibit considerable
      contraction in side chain end-to-end distance and were observed to be nearly
      isoenergetic using B3LYP, but the folded structures with the ether oxygen atoms
      in gauche conformations were ~1.5 kcal/mol lower in energy using B97D. Below the
      second ether linkage of the Nafion side chain, the rotational potential energy
      profiles were identical to that determined for the SSC side chain. The 3M side
      chain was generally found to be the most rigid with barriers for complete
      rotation about the central carbon-carbon bonds of approximately 7 kcal/mol. These
      results indicate that minor differences in side chain length and chemistry may
      have a pronounced effect on the rotational potential energy surfaces,
      particularly those involving rotation about different carbon-carbon bonds with
      distinctly different character.

PMID- 24041416
TI  - [Infections caused by multi-resistant Gram-positive bacteria (Staphylococcus
      aureus and Enterococcus spp.)].
AB  - Methicillin -resistant Staphylocccus aureus (MRSA) and multirresistant
      entorococci are still problematic in nosocomial infections and new challenges
      have emerged for their containment. MRSA has increased the multiresistant
      profile; it has been described vancomycin and linezolid resistant isolates and
      isolates with decreased daptomycin susceptibility. Moreover, new clones (ST398)
      have emerged, initially associated with piggeries, and new mec variants (mecC)
      with livestock origin that escape to the detection with current molecular methods
      based on mecA gene have been detected. In enterococci, linzeolid resistant
      isolates and isolates with deceased susceptibility to daptomycin have been
      described. Moreover, ampicillin resistant Enterococcus faecium due to beta
      lactamase production has been recently found in Europe. Control of MRSA isolates
      and multiresistant enteroccocci should combined antibiotic stewardship strategies
      and epidemiological measures, including detection of colonized patients in order
      to reduce colonization pressure and their transmission.

PMID- 24041418
TI  - Sinus Augmentation With Platelet-Rich Fibrin in Combination With Bovine Bone
      Graft Versus Bovine Bone Graft in Combination With Collagen Membrane.
AB  - The purpose of this study was to compare the efficacy between the use of bovine
      bone graft material and platelet-rich fibrin (PRF) mixture (test group) and
      bovine bone graft material and collagen membrane combination (control group) in 2
      stage maxillary sinus augmentation. According to specific inclusion/exclusion
      criteria, patients treated between 2008 and 2012 were selected. Panoramic
      radiographs were used for radiologic assessments. To evaluate the relationship
      between sinus-graft height and each implant, the bone level (BL) was divided by
      implant length (IL). To evaluate the change in the height of grafted sinus, the
      grafted sinus floor above the lowest part of the original sinus height (GSH) was
      divided by the original sinus height (OSH). Samples taken during implant surgery
      were used for histologic and histomorphometric analyses. Twenty-five patients, 32
      augmentation surgeries, and 66 one-stage implants were included in the study. No
      implant loss or complication was observed in either group. There were no
      statistical differences according to new bone formation (P = .61) and biomaterial
      remnant (P = .87). During the evaluation period, the test group showed
      statistically less change in the BL/IL ratio (P = .022). The difference of
      GSH/OSH ratio was found to be insignificant between groups (P = .093). It was
      observed that the grafted sinus covering the implant apex and sinus floor was
      above the original sinus height in both groups. It may be concluded from this
      study that both combinations can be successfully used for sinus augmentation.
      Further studies evaluating different graft materials and PRF combinations in the
      early phases of healing would be beneficial. 

PMID- 24041419
TI  - Release of quantum dot nanoparticles in porous media: role of cation exchange and
      aging time.
AB  - Understanding the fate and transport of engineered nanoparticles (ENPs) in
      subsurface environments is required for developing the best strategy for waste
      management and disposal of these materials. In this study, the deposition and
      release of quantum dot (QD) nanoparticles were studied in saturated sand columns.
      The QDs were first deposited in columns using 100 mM NaCl or 2 mM CaC12
      solutions. Deposited QDs were then contacted with deionized (DI) water and/or
      varying Na(+) concentrations to induce release. QDs deposited in 100 mM Na(+)
      were easily reversible when the column was rinsed with DI water. Conversely, QDs
      deposited in the presence of Ca(2+) exhibited resistance to release with DI
      water. However, significant release occurred when the columns were flushed with
      NaCl solutions. This release behavior was explained by cation exchange (Ca(2+) in
      exchange sites were replaced by Na(+)) which resulted in the breakdown of calcium
      bridging. We also studied the effect of aging time on the QD release. As the
      aging time increased, smaller amounts of QDs were released following cation
      exchange. However, deposited QDs were subsequently released when the column was
      flushed with DI water. The release behavior was modeled using a single first
      order kinetic release process and changes in the maximum solid phase
      concentration of deposited QDs with transition in solution chemistry. The results
      of this study demonstrate that the presence of carboxyl groups on ENPs and
      divalent ions in the solution plays a key role in controlling ENP mobility in the
      subsurface environment. 

PMID- 24041420
TI  - Synthetic biology at all scales.

PMID- 24041421
TI  - Fabrication and catalytic performance of highly stable multifunctional core-shell
      zeolite composites.
AB  - Multifunctional Fe3O4@SiO2-Au@silicalite-1 core-shell magnetic zeolite composites
      were fabricated by combining a series of sol-gel process and vapor-phase transfer
      of silicalite-1 zeolite nanocrystal-seeded silica shells. The obtained composite
      has high magnetization (32.00 emu/g), stably confined and active gold
      nanoparticles (ca. 15 nm), and a hierarchical silicalite-1 outer shell. The core
      shell composite exhibits a high efficiency of magnetic separability, excellent
      catalytic performance, and reusability for the reduction of 4-nitrophenol with
      conversion of 98% in 12 min. Moreover, it preserves a good stability after a high
      temperature hydrothermal treatment. 

PMID- 24041422
TI  - Arginine and disordered amyloid-beta peptide structures: molecular level insights
      into the toxicity in Alzheimer's disease.
AB  - Recent studies present that the single arginine (R) residue in the sequence of
      Abeta42 adopts abundant beta-sheet structure and forms stable salt bridges with
      various residues. Furthermore, experiments proposed that R stimulates the Abeta
      assembly and arginine (R) to alanine (A) mutation (R5A) decreases both aggregate
      formation tendency and the degree of its toxicity. However, the exact roles of R
      and R5A mutation in the structures of Abeta42 are poorly understood. Extensive
      molecular dynamics simulations along with thermodynamic calculations present that
      R5A mutation impacts the structures and free energy landscapes of the aqueous
      Abeta42 peptide. The beta-sheet structure almost disappears in the Ala21-Ala30
      region but is more abundant in parts of the central hydrophobic core and C
      terminal regions of Abeta42 upon R5A mutation. More abundant alpha-helix is
      adopted in parts of the N-terminal and mid-domain regions and less prominent
      alpha-helix formation occurs in the central hydrophobic core region of Abeta42
      upon R5A mutation. Interestingly, intramolecular interactions between N- and C
      terminal or mid-domain regions disappear upon R5A mutation. The structures of
      Abeta42 are thermodynamically less stable and retain reduced compactness upon R5A
      mutation. R5A mutant-type structure stability increases with more prominent
      central hydrophobic core and mid-domain or C-terminal region interactions. Based
      on our results reported in this work, small organic molecules and antibodies that
      avoid beta-sheet formation in the Ala21-Ala30 region and hinder the
      intramolecular interactions occurring between the N-terminal and mid-domain or C
      terminal regions of Abeta42 may help to reduce Abeta42 toxicity in Alzheimer's
      disease. 

PMID- 24041423
TI  - Cytocompatibility, osseointegration, and bioactivity of three-dimensional porous
      and nanostructured network on polyetheretherketone.
AB  - Porous biomaterials with the proper three-dimensional (3D) surface network can
      enhance biological functionalities especially in tissue engineering, but it has
      been difficult to accomplish this on an important biopolymer,
      polyetheretherketone (PEEK), due to its inherent chemical inertness. In this
      study, a 3D porous and nanostructured network with bio-functional groups is
      produced on PEEK by sulfonation and subsequent water immersion. Two kinds of
      sulfonation-treated PEEK (SPEEK) samples, SPEEK-W (water immersion and rinsing
      after sulfonation) and SPEEK-WA (SPEEK-W with further acetone rinsing) are
      prepared. The surface characteristics, in vitro cellular behavior, in vivo
      osseointegration, and apatite-forming ability are systematically investigated by
      X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy,
      scanning electron microscopy, cell adhesion and cell proliferation assay, real
      time RT-PCR analysis, micro-CT evaluation, push-out tests, and immersion tests.
      SPEEK-WA induces pre-osteoblast functions including initial cell adhesion,
      proliferation, and osteogenic differentiation in vitro as well as substantially
      enhanced osseointegration and bone-implant bonding strength in vivo and apatite
      forming ability. Although SPEEK-W has a similar surface morphology and chemical
      composition as SPEEK-WA, its cytocompatibility is inferior due to residual
      sulfuric acid. Our results reveal that the pre-osteoblast functions, bone growth,
      and apatite formation on the SPEEK surfaces are affected by many factors,
      including positive effects introduced by the 3D porous structure and SO3H groups
      as well as negative ones due to the low pH environment. Surface functionalization
      broadens the use of PEEK in orthopedic implants.

PMID- 24041424
TI  - Optimization of Tet1 ligand density in HPMA-co-oligolysine copolymers for
      targeted neuronal gene delivery.
AB  - Targeted gene delivery vectors can enhance cellular specificity and transfection
      efficiency. We demonstrated previously that conjugation of Tet1, a peptide that
      binds to the GT1b ganglioside, to polyethylenimine results in preferential
      transfection of neural progenitor cells in vivo. In this work, we investigate the
      effect of Tet1 ligand density on gene delivery to neuron-like, differentiated PC
      12 cells. A series of statistical, cationic peptide-based polymers containing
      various amounts (1-5 mol%) of Tet1 were synthesized via one-pot reversible
      addition-fragmentation chain transfer (RAFT) polymerization by copolymerization
      of Tet1 and oligo-l-lysine macromonomers with N-(2-hydroxypropyl)methacrylamide
      (HPMA). When complexed with plasmid DNA, the resulting panel of Tet1
      functionalized polymers formed particles with similar particle size as particles
      formed with untargeted HPMA-oligolysine copolymers. The highest cellular uptake
      in neuron-like differentiated PC-12 cells was observed using polymers with
      intermediate Tet1 peptide incorporation. Compared to untargeted polymers,
      polymers with optimal incorporation of Tet1 increased gene delivery to neuron
      like PC-12 cells by over an order of magnitude but had no effect compared to
      control polymers in transfecting NIH/3T3 control cells.

PMID- 24041425
TI  - Three-dimensional neuron-muscle constructs with neuromuscular junctions.
AB  - This paper describes a fabrication method of muscle tissue constructs driven by
      neurotransmitters released from activated motor neurons. The constructs consist
      of three-dimensional (3D) free-standing skeletal muscle fibers co-cultured with
      motor neurons. We differentiated mouse neural stem cells (mNSCs) cultured on the
      skeletal muscle fibers into neurons that extend their processes into the muscle
      fibers. We found that acetylcholine receptors (AChRs) were formed at the
      connection between the muscle fibers and the neurons. The neuron-muscle
      constructs consist of highly aligned, long and matured muscle fibers that
      facilitate wide contractions of muscle fibers in a single direction. The
      contractions of the neuron-muscle construct were observed after glutamic acid
      activation of the neurons. The contraction was stopped by treatment with curare,
      an neuromuscular junction (NMJ) antagonist. These results indicate that our
      method succeeded in the formation of NMJs in the neuron-muscle constructs. The
      neuron-muscle construct system can potentially be used in pharmacokinetic assays
      related to NMJ disease therapies and in soft-robotic actuators.

PMID- 24041426
TI  - Modulation of keratocyte phenotype by collagen fibril nanoarchitecture in
      membranes for corneal repair.
AB  - Type I collagen membranes with tailored fibril nanoarchitectures were fabricated
      through a vitrification processing, which mimicked, to a degree, the collagen
      maturation process of corneal stromal extracellular matrix in vivo. Vitrification
      was performed at a controlled temperature of either 5  degrees C or 39  degrees C
      at a constant relative humidity of 40% for various time periods from 0.5 wk up to
      8 wk. During vitrification, the vitrified collagen membranes (collagen vitrigels,
      CVs) exhibited a rapid growth in fibrillar density through the evaporation of
      water and an increase in fibrillar stiffness due to the formation of new and/or
      more-stable interactions. On the other hand, the collagen fibrils in CVs
      maintained their D-periodicity and showed no significant difference in fibrillar
      diameter, indicating preservation of the native states of the collagen fibrils
      during vitrification. Keratocyte phenotype was maintained on CVs to varying
      degrees that were strongly influenced by the collagen fibril nanoarchitectures.
      Specifically, the vitrification time of CVs mainly governed the keratocyte
      morphology, showing significant increases in the cell protrusion number,
      protrusion length, and cell size along with CV vitrification time. The CV
      vitrification temperature affected the regulation of keratocyte fibroblasts' gene
      expressions, including keratocan and aldehyde dehydrogenase (ALDH), demonstrating
      a unique way to control the expression of specific genes in vitro.

PMID- 24041427
TI  - Contextualisation in the revised dual representation theory of PTSD: a response
      to Pearson and colleagues.
AB  - Three recent studies (Pearson, 2012; Pearson, Ross, & Webster, 2012) purported to
      test the revised dual representation theory of posttraumatic stress disorder
      (Brewin, Gregory, Lipton, & Burgess, 2010) by manipulating the amount of
      additional information accompanying traumatic stimulus materials and assessing
      the effect on subsequent intrusive memories. Here we point out that these studies
      involve a misunderstanding of the meaning of "contextual" within the theory, such
      that the manipulation would be unlikely to have had the intended effect and the
      results are ambiguous with respect to the theory. Past and future experimental
      tests of the theory are discussed. 

PMID- 24041429
TI  - Surface thermodynamic analysis of fluid confined in a cone and comparison with
      the sphere-plate and plate-plate geometries.
AB  - The behavior of pure fluid confined in a cone is investigated using thermodynamic
      stability analysis. Four situations are explained on the basis of the initial
      confined phase (liquid/vapor) and its pressure (above/below the saturation
      pressure). Thermodynamic stability analysis (a plot of the free energy of the
      system versus the size of the new potential phase) reveals whether the phase
      transition is possible and, if so, the number and type
      (unstable/metastable/stable) of equilibrium states in each of these situations.
      Moreover we investigated the effect of the equilibrium contact angle and the cone
      angle (equivalent to the confinement's surface separation distance) on the free
      energy (potential equilibrium states). The results are then compared to our
      previous study of pure fluid confined in the gap between a sphere and a flat
      plate and the gap between two flat plates.1 Confined fluid behavior of the four
      possible situations (for these three geometries) can be explained in a unified
      framework under two categories based on only the meniscus shape (concave/convex).
      For systems with bulk-phase pressure imposed by a reservoir, the stable
      coexistence of pure liquid and vapor is possible only when the meniscus is
      concave. 

PMID- 24041428
TI  - Genes related to antiviral activity, cell migration, and lysis are differentially
      expressed in CD4(+) T cells in human t cell leukemia virus type 1-associated
      myelopathy/tropical spastic paraparesis patients.
AB  - Human T cell leukemia virus type 1 (HTLV-1) preferentially infects CD4(+) T cells
      and these cells play a central role in HTLV-1 infection. In this study, we
      investigated the global gene expression profile of circulating CD4(+) T cells
      from the distinct clinical status of HTLV-1-infected individuals in regard to TAX
      expression levels. CD4(+) T cells were isolated from asymptomatic HTLV-1 carrier
      (HAC) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
      patients in order to identify genes involved in HAM/TSP development using a
      microarray technique. Hierarchical clustering analysis showed that healthy
      control (CT) and HTLV-1-infected samples clustered separately. We also observed
      that the HAC and HAM/TSP groups clustered separately regardless of TAX
      expression. The gene expression profile of CD4(+) T cells was compared among the
      CT, HAC, and HAM/TSP groups. The paxillin (Pxn), chemokine (C-X-C motif )
      receptor 4 (Cxcr4), interleukin 27 (IL27), and granzyme A (Gzma) genes were
      differentially expressed between the HAC and HAM/TSP groups, regardless of TAX
      expression. The perforin 1 (Prf1) and forkhead box P3 (Foxp3) genes were
      increased in the HAM/TSP group and presented a positive correlation to the
      expression of TAX and the proviral load (PVL). The frequency of CD4(+)FOXP3(+)
      regulatory T cells (Treg) was higher in HTLV-1-infected individuals. Foxp3 gene
      expression was positively correlated with cell lysis-related genes (Gzma, Gzmb,
      and Prf1). These findings suggest that CD4(+) T cell activity is distinct between
      the HAC and HAM/TSP groups.

PMID- 24041430
TI  - CT scan-detected pneumoperitoneum: an unreliable predictor of intra-abdominal
      injury in blunt trauma.
AB  - INTRODUCTION: Free intra-peritoneal air in blunt trauma is a classic sign
      associated with hollow viscus injury, traditionally mandating laparotomy. In
      blunt abdominal trauma, the CT scan has become the diagnostic modality of choice.
      The increased sensitivity of CT scans may lead to detection of free intra
      peritoneal air that is not clinically significant. OBJECTIVE: To characterize
      conditions and findings that allow for the safe observation of blunt trauma
      patients with free air and to propose a patient management algorithm to decrease
      rates of non-therapeutic laparotomy. DESIGN: A retrospective review of 5877 blunt
      trauma patients who had an abdominal CT scan upon admission to our hospital from
      2003 to 2011. A secondary CT review was performed by a single radiologist to
      further characterize the CT findings in the 74 patients with free air reported on
      initial scan. Management and hospital course were reviewed in these patients.
      RESULTS: Of the 74 patients with intra-abdominal free air, 36 patients with a
      benign clinical picture were observed and 38 patients underwent urgent
      exploratory laparotomy. Eleven patients received a non-therapeutic laparotomy.
      The majority (61%) of patients, 45 of 74, had free air and no significant injury
      suggesting the presence of benign free air. Patients who had intra-abdominal
      injury also typically had other clinical or radiologic signs of injury. Findings
      that were highly predictive of intra-abdominal injury in the setting of free air
      were free fluid (P<0.001), radiographic signs of bowel trauma (P<0.001) as well
      as clinical and/or radiographic seatbelt sign (P=0.004). CONCLUSIONS: CT scans
      may detect free air that is not always clinically significant. Free fluid,
      seatbelt sign or radiographic signs of bowel trauma in the presence of
      pneumoperitoneum is highly predictive of injury and these patients should be
      explored. Based on the results of our study, we created an algorithm to aid in
      identifying those patients with intra-abdominal free air who may be observed
      safely.

PMID- 24041431
TI  - Isolated fracture of anterior arch of atlas in a child: case report and review of
      the literature.

PMID- 24041432
TI  - Head movement during CT brain perfusion acquisition of patients with suspected
      acute ischemic stroke.
AB  - OBJECTIVE: Computed Tomography Perfusion (CTP) is a promising tool to support
      treatment decision for acute ischemic stroke patients. However, head movement
      during acquisition may limit its applicability. Information of the extent of head
      motion is currently lacking. Our purpose is to qualitatively and quantitatively
      assess the extent of head movement during acquisition. METHODS: From 103
      consecutive patients admitted with suspicion of acute ischemic stroke, head
      movement in 220 CTP datasets was qualitatively categorized by experts as none,
      minimal, moderate, or severe. The movement was quantified using 3D registration
      of CTP volume data with non-contrast CT of the same patient; yielding 6 movement
      parameters for each time frame. The movement categorization was correlated with
      National Institutes of Health Stroke Scale (NIHSS) score and baseline
      characteristic using multinomial logistic regression and student's t-test
      respectively. RESULTS: Moderate and severe head movement occurred in almost 25%
      (25/103) of all patients with acute ischemic stroke. The registration technique
      quantified head movement with mean rotation angle up to 3.6 degrees  and 14
      degrees , and mean translation up to 9.1mm and 22.6mm for datasets classified as
      moderate and severe respectively. The rotation was predominantly in the axial
      plane (yaw) and the main translation was in the scan direction. There was no
      statistically significant association between movement classification and NIHSS
      score and baseline characteristics. CONCLUSIONS: Moderate or severe head movement
      during CTP acquisition of acute stroke patients is quite common. The presented
      registration technique can be used to automatically quantify the movement during
      acquisition, which can assist identification of CTP datasets with excessive head
      movement.

PMID- 24041433
TI  - Tibial hyperostosis: a diagnostic approach.
AB  - Tibial hyperostosis may be encountered in musculoskeletal imaging, incidentally
      or during the investigation of a leg pain. Hyperostosis involves the exuberant
      production of osseous tissue and results in cortical, periosteal and/or endosteal
      thickening of the bone. As a long bone with thick cortices, the tibia has a
      significant probability of being affected by ubiquitous bone diseases. As a
      tubular long bone, the tibia is likely to be involved in extensive infectious
      conditions such as osteomyelitis. As a bone of the lower limb, the tibia
      undergoes high stresses and may be affected by decrease in bone strength or
      repetitive submaximal stress. The tibia is also particularly involved in some
      bone sclerosing dysplasias and Paget's disease. In this work, we aim at
      highlighting the main conditions leading to tibial hyperostosis and try to
      provide key elements to narrow down the several diagnostic possibilities. Osteoid
      osteomas, fatigue or insufficiency fractures, infectious conditions, vascular
      lesions, sclerosing bone dysplasias and Paget's disease represent the main
      challenging diagnoses to discuss. 

PMID- 24041434
TI  - Non-contrast-enhanced preoperative assessment of lung perfusion in patients with
      non-small-cell lung cancer using Fourier decomposition magnetic resonance
      imaging.
AB  - OBJECTIVE: To investigate non-contrast-enhanced Fourier decomposition MRI (FD
      MRI) for assessment of regional lung perfusion in patients with Non-Small-Cell
      Lung Cancer (NSCLC) in comparison to dynamic contrast-enhanced MRI (DCE MRI).
      METHODS: Time-resolved non-contrast-enhanced images of the lungs were acquired
      prospectively in 15 patients using a 2D balanced steady-state free precession (b
      SSFP) sequence. After non-rigid registration of the native image data, perfusion
      weighted images were calculated by separating periodic changes of lung proton
      density at the cardiac frequency using FD. DCE MRI subtraction datasets were
      acquired as standard of reference. Both datasets were analyzed visually for
      perfusion defects. Then segmentation analyses were performed to describe
      perfusion of pulmonary lobes semi-quantitatively as percentages of total lung
      perfusion. Overall FD MRI perfusion signal was compared to velocity-encoded flow
      measurements in the pulmonary trunk as an additional fully quantitative
      reference. RESULTS: Image quality ratings of FD MRI were significantly inferior
      to those of DCE MRI (P<0.0001). Sensitivity, specificity, and accuracy of FD MRI
      for visual detection of perfusion defects were 84%, 92%, and 91%. Semi
      quantitative evaluation of lobar perfusion provided high agreement between FD MRI
      and DCE MRI for both entire lungs and upper lobes, but less agreement in the
      lower parts of both lungs. FD perfusion signal showed high linear correlation
      with pulmonary arterial blood flow. CONCLUSION: FD MRI is a promising technique
      that allows for assessing regional lung perfusion in NSCLC patients without
      contrast media or ionizing radiation. However, for being applied in clinical
      routine, image quality and robustness of the technique need to be further
      improved.

PMID- 24041435
TI  - Qualitative pattern classification of shear wave elastography for breast masses:
      how it correlates to quantitative measurements.
AB  - OBJECTIVE: To determine the correlation of qualitative shear wave elastography
      (SWE) pattern classification to quantitative SWE measurements and whether it is
      representative of quantitative SWE values with similar performances. METHODS:
      From October 2012 to January 2013, 267 breast masses of 236 women (mean age:
      45.12 +/- 10.54 years, range: 21-88 years) who had undergone ultrasonography
      (US), SWE, and subsequent biopsy were included. US BI-RADS final assessment and
      qualitative and quantitative SWE measurements were recorded. Correlation between
      pattern classification and mean elasticity, maximum elasticity, elasticity ratio
      and standard deviation were evaluated. Diagnostic performances of grayscale US,
      SWE parameters, and US combined to SWE values were calculated and compared.
      RESULTS: Of the 267 breast masses, 208 (77.9%) were benign and 59 (22.1%) were
      malignant. Pattern classifications significantly correlated with all quantitative
      SWE measurements, showing highest correlation with maximum elasticity, r = 0.721
      (P<0.001). Sensitivity was significantly decreased in US combined to SWE
      measurements to grayscale US: 69.5-89.8% to 100.0%, while specificity was
      significantly improved: 62.5-81.7% to 13.9% (P<0.001). Area under the ROC curve
      (Az) did not show significant differences between grayscale US to US combined to
      SWE (P>0.05). CONCLUSION: Pattern classification shows high correlation to
      maximum stiffness and may be representative of quantitative SWE values. When
      combined to grayscale US, SWE improves specificity of US.

PMID- 24041436
TI  - Prospective randomized study of contrast reaction management curricula: computer
      based interactive simulation versus high-fidelity hands-on simulation.
AB  - PURPOSE: We developed a computer-based interactive simulation program for
      teaching contrast reaction management to radiology trainees and compared its
      effectiveness to high-fidelity hands-on simulation training. MATERIALS AND
      METHODS: IRB approved HIPAA compliant prospective study of 44 radiology
      residents, fellows and faculty who were randomized into either the high-fidelity
      hands-on simulation group or computer-based simulation group. All participants
      took separate written tests prior to and immediately after their intervention.
      Four months later participants took a delayed written test and a hands-on high
      fidelity severe contrast reaction scenario performance test graded on predefined
      critical actions. RESULTS: There was no statistically significant difference
      between the computer and hands-on groups' written pretest, immediate post-test,
      or delayed post-test scores (p>0.6 for all). Both groups' scores improved
      immediately following the intervention (p<0.001). The delayed test scores 4
      months later were still significantly higher than the pre-test scores (p <=
      0.02). The computer group's performance was similar to the hands-on group on the
      severe contrast reaction simulation scenario test (p = 0.7). There were also no
      significant differences between the computer and hands-on groups in performance
      on the individual core competencies of contrast reaction management during the
      contrast reaction scenario. CONCLUSION: It is feasible to develop a computer
      based interactive simulation program to teach contrast reaction management.
      Trainees that underwent computer-based simulation training scored similarly on
      written tests and on a hands-on high-fidelity severe contrast reaction scenario
      performance test as those trained with hands-on high-fidelity simulation.

PMID- 24041437
TI  - Utility of dual phase liver CT for metastatic melanoma staging and surveillance.
AB  - RATIONALE AND OBJECTIVES: To evaluate the clinical utility of dual phase computed
      tomography (CT) for assessment of hepatic metastases in patients with metastatic
      melanoma. MATERIALS AND METHODS: A retrospective case-control study of dual phase
      CT examinations consisting of late hepatic arterial and portal venous phases
      performed on patients with melanoma was undertaken. In 2010, 420 dual phase CT
      examinations were performed on 188 patients. Of these, 46 CT examinations on 24
      patients with hepatic metastases were combined with 52 control studies for
      evaluation. Two blinded reviewers independently evaluated single portal venous
      phase alone and dual phase imaging on separate occasions. The presence of hepatic
      lesions, the conspicuity of the lesions, and the likelihood that the detected
      lesions were metastases was recorded. Agreement between readers, sensitivity and
      specificity was calculated. RESULTS: In no case was hepatic metastatic disease
      only apparent on arterial phase imaging. Arterially enhancing hepatic lesions
      only visible on the arterial phase or much more conspicuous on the arterial phase
      were present in 10 studies (10%), all of which were benign. Liver metastases were
      rated as being more accurately assessed on the portal venous phase in up to 100%.
      In a per scan analysis dual phase and venous phase imaging had similar
      sensitivities of 96% (95%, CI: 86-100) and 98% (95%, CI: 89-100), respectively.
      CONCLUSION: Single portal venous phase imaging is adequate for staging and
      surveillance in patients with metastatic melanoma.

PMID- 24041438
TI  - Global N-acetylaspartate concentration in benign and non-benign multiple
      sclerosis patients of long disease duration.
AB  - BACKGROUND AND OBJECTIVE: To examine whether clinically benign multiple sclerosis
      patients (BMS) show similar losses of their global N-acetylaspartate (NAA)
      neuronal marker relative to more clinically disabled patients of similar disease
      duration. METHODS: The whole-brain NAA concentration (WBNAA) was acquired with
      whole-head non-localizing proton MR spectroscopy. Fractional brain parenchymal
      volume (fBPV), T2 and T1 lesion loads, were obtained from the MRI in: (i) 24 BMS
      patients: 23.1 +/- 7.2 years disease duration, median Expanded Disability Status
      Scale (EDSS) score of 2.0 (range: 0-3); (ii) 26 non-benign MS patients (non-BMS),
      24.5 +/- 7.4 years disease duration, median EDSS of 4.0 (range: 3.5-6.5); (iii)
      15 healthy controls. RESULTS: Controls' 12.4 +/- 2.3mM WBNAA was significantly
      higher than the BMS's and non-BMS's 10.5 +/- 2.4 and 9.9 +/- 2.1mM (both p<0.02),
      but the difference between the patients' groups was not (p>0.4). Likewise, the
      controls' 81.2 +/- 4.5% fBPV exceeded the BMS and non-BMS's 77.0 +/- 5.8% and
      76.3 +/- 8.6% (p<0.03), which were also not different from one another (p>0.7).
      BMS patients' T1-hypointense lesion load, 2.1 +/- 2.2 cm(3), was not
      significantly different than the non-BMS's 4.1 +/- 5.4 cm(3) (p>0.08) and T2
      hyperintense loads: 6.0 +/- 5.7 cm(3) and 8.7 +/- 7.8 cm(3), were also not
      different (p>0.1). CONCLUSIONS: WBNAA differentiates normal controls from MS
      patients but does not distinguish BMS from more disabled MS patients of similar
      disease duration. Nevertheless, all MS patients who remain RR for 15+ years
      suffered WBNAA loss similar to the average RR MS population at fourfold shorter
      disease duration suggesting relative global neuronal sparing or leveling-off of
      the neurodegeneration rate.

PMID- 24041439
TI  - Revising the WHO verbal autopsy instrument to facilitate routine cause-of-death
      monitoring.
AB  - OBJECTIVE: Verbal autopsy (VA) is a systematic approach for determining causes of
      death (CoD) in populations without routine medical certification. It has mainly
      been used in research contexts and involved relatively lengthy interviews. Our
      objective here is to describe the process used to shorten, simplify, and
      standardise the VA process to make it feasible for application on a larger scale
      such as in routine civil registration and vital statistics (CRVS) systems.
      METHODS: A literature review of existing VA instruments was undertaken. The World
      Health Organization (WHO) then facilitated an international consultation process
      to review experiences with existing VA instruments, including those from WHO, the
      Demographic Evaluation of Populations and their Health in Developing Countries
      (INDEPTH) Network, InterVA, and the Population Health Metrics Research Consortium
      (PHMRC). In an expert meeting, consideration was given to formulating a workable
      VA CoD list [with mapping to the International Classification of Diseases and
      Related Health Problems, Tenth Revision (ICD-10) CoD] and to the viability and
      utility of existing VA interview questions, with a view to undertaking systematic
      simplification. FINDINGS: A revised VA CoD list was compiled enabling mapping of
      all ICD-10 CoD onto 62 VA cause categories, chosen on the grounds of public
      health significance as well as potential for ascertainment from VA. A set of 221
      indicators for inclusion in the revised VA instrument was developed on the basis
      of accumulated experience, with appropriate skip patterns for various population
      sub-groups. The duration of a VA interview was reduced by about 40% with this new
      approach. CONCLUSIONS: The revised VA instrument resulting from this consultation
      process is presented here as a means of making it available for widespread use
      and evaluation. It is envisaged that this will be used in conjunction with
      automated models for assigning CoD from VA data, rather than involving
      physicians.

PMID- 24041440
TI  - Reducing exciton binding energy by increasing thin film permittivity: an
      effective approach to enhance exciton separation efficiency in organic solar
      cells.
AB  - Photocurrent generation in organic solar cells requires that excitons, which are
      formed upon light absorption, dissociate into free carriers at the interface of
      electron acceptor and donor materials. The high exciton binding energy, arising
      from the low permittivity of organic semiconductor films, generally causes low
      exciton separation efficiency and subsequently low power conversion efficiency.
      We demonstrate here, for the first time, that the exciton binding energy in B,O
      chelated azadipyrromethene (BO-ADPM) donor films is reduced by increasing the
      film permittivity by blending the BO-ADPM donor with a high dielectric constant
      small molecule, camphoric anhydride (CA). Various spectroscopic techniques,
      including impedance spectroscopy, photon absorption and emission spectroscopies,
      as well as X-ray spectroscopies, are applied to characterize the thin film
      electronic and photophysical properties. Planar heterojunction solar cells are
      fabricated with a BO-ADPM:CA film as the electron donor and C60 as the acceptor.
      With an increase in the dielectric constant of the donor film from ~4.5 to ~11,
      the exciton binding energy is reduced and the internal quantum efficiency of the
      photovoltaic cells improves across the entire spectrum, with an ~30% improvement
      in the BO-ADPM photoactive region. 

PMID- 24041441
TI  - Traditional medicine practitioners' knowledge and views on treatment of pregnant
      women in three regions of Mali.
AB  - BACKGROUND: Despite the widespread use of medicinal plants in Mali, knowledge
      about how traditional practitioners (TPs) treat pregnant and lactating women is
      lacking. AIM OF THE STUDY: The aim of this study was to investigate how
      traditional practitioners in Mali treat common diseases and ailments during
      pregnancy. METHODS: Data was collected through structured interviews of
      traditional practitioners in one urban (Bamako) and two rural areas (Siby and
      Dioila) in Mali. The TPs were interviewed about how they treat common diseases
      and ailments during pregnancy. They were also asked to name harmful plants in
      pregnancy and plants that could affect breast milk production. In addition, we
      asked about nine specific medicinal plants commonly used in Mali; Opilia
      amentacea (syn. Opilia celtidifolia), Ximenia americana, Cola cordifolia,
      Combretum glutinosum, Parkia biglobosa, Trichilia emetica, Combretum micranthum,
      Lippia chevalieri and Vepris heterophylla. RESULTS: A total of 72 traditional
      practitioners (64% women, age: 34 to 90 years) were interviewed during an eight
      week period October 2011 to December 2011. They treated between 1 and 30 pregnant
      women with medicinal plants per months. We found a relatively high consensus for
      treatment of pregnant women with common diseases and ailments like nausea and
      dermatitis. The highest informer consensus was found for the treatment of malaria
      during pregnancy. TPs generally recommended pregnant women to avoid medicinal
      plants with bitter tastes like stem and root bark of Khaya senegalensis and
      Opilia amentacea (syn. Opilia celtidifolia). TPs distinguished between oral
      (potentially unsafe) and dermal use (safe) of Opilia amentacea (syn. Opilia
      celtidifolia). Cola cordifolia was used to facilitate labor. CONCLUSION:
      Experience and knowledge about treatment of pregnant women with medicinal plants
      was broad among the traditional practitioners in the three investigated regions
      in Mali. Collaborating with traditional practitioners on the safe use of
      medicinal plants in pregnancy may promote safer pregnancies and better health for
      mothers and their unborn infants in Mali.

PMID- 24041442
TI  - Peach genetic resources: diversity, population structure and linkage
      disequilibrium.
AB  - BACKGROUND: Peach (Prunus persica (L.) Batsch) is one of the most important model
      fruits in the Rosaceae family. Native to the west of China, where peach has been
      domesticated for more than 4,000 years, its cultivation spread from China to
      Persia, Mediterranean countries and to America. Chinese peach has had a major
      impact on international peach breeding programs due to its high genetic
      diversity. In this research, we used 48 highly polymorphic SSRs, distributed over
      the peach genome, to investigate the difference in genetic diversity, and linkage
      disequilibrium (LD) among Chinese cultivars, and North American and European
      cultivars, and the evolution of current peach cultivars. RESULTS: In total, 588
      alleles were obtained with 48 SSRs on 653 peach accessions, giving an average of
      12.25 alleles per locus. In general, the average value of observed heterozygosity
      (0.47) was lower than the expected heterozygosity (0.60). The separate analysis
      of groups of accessions according to their origin or reproductive strategies
      showed greater variability in Oriental cultivars, mainly due to the high level of
      heterozygosity in Chinese landraces. Genetic distance analysis clustered the
      cultivars into two main groups: one included four wild related Prunus, and the
      other included most of the Oriental and Occidental landraces and breeding
      cultivars. STRUCTURE analysis assigned 469 accessions to three subpopulations:
      Oriental (234), Occidental (174), and Landraces (61). Nested STRUCTURE analysis
      divided the Oriental subpopulation into two different subpopulations: 'Yu Lu' and
      'Hakuho'. The Occidental breeding subpopulation was also subdivided into
      nectarine and peach subpopulations. Linkage disequilibrium (LD) analysis in each
      of these subpopulations showed that the percentage of linked (r2 > 0.1) intra
      chromosome comparisons ranged between 14% and 47%. LD decayed faster in Oriental
      (1,196 Kbp) than in Occidental (2,687 Kbp) samples. In the 'Yu Lu' subpopulation
      there was considerable LD extension while no variation of LD with physical
      distance was observed in the landraces. From the first STRUCTURE result, LG1 had
      the greatest proportion of alleles in LD within all three subpopulations.
      CONCLUSIONS: Our study demonstrates a high level of genetic diversity and
      relatively fast decay of LD in the Oriental peach breeding program. Inclusion of
      Chinese landraces will have a greater effect on increasing genetic diversity in
      Occidental breeding programs. Fingerprinting with genotype data for all 658
      cultivars will be used for accession management in different germplasms. A higher
      density of markers are needed for association mapping in Oriental germplasm due
      to the low extension of LD. Population structure and evaluation of LD provides
      valuable information for GWAS experiment design in peach.

PMID- 24041443
TI  - Teachers' assessments of children's mental problems with respect to adolescents'
      subsequent self-reported mental health.
AB  - PURPOSE: To investigate whether teachers' assessments of children are predictive
      of subsequent self-reported mental problems in adolescence and how these problems
      are concurrently linked with adolescents' overall life satisfaction. METHOD: The
      study subjects originated from the prospective population-based Northern Finland
      Birth Cohort 1986 (N = 9,432). At age 8 years first-grade students' emotional and
      behavioral problems were assessed by their teachers with Rutter Children's
      Behavioural Questionnaires for teachers (RB2). At the age of 16 years,
      adolescents responded to the eight Youth Self-report (YSR) subscales and the one
      item overall life satisfaction scale. Multivariate logistic regression was used
      to study the longitudinal relationship between RB2 and YSR. RESULTS: Children who
      had emotional problems according to their teachers (RB2) were more prone to
      withdrawal and social problems in adolescence (YSR). Behavioral problems in
      childhood (RB2) were predictive of attention problems, and delinquent and
      aggressive behavior (YSR), while hyperactivity (RB2) was only predictive of
      attention problems and delinquent behavior (YSR). Additionally, each YSR subscale
      was strongly and linearly associated with concurrent self-reported life
      satisfaction in adolescence. CONCLUSIONS: Teachers' assessments of children were
      predictive of self-reported mental problems in adolescence, which, in turn, were
      strongly associated with concurrent self-reported life satisfaction. In order to
      support favorable growth of children to well-adjusted adolescents and to
      intervene as early as possible in the event of adverse progression, both
      teachers' assessments of children and adolescent's self-rated overall life
      satisfaction should be acknowledged.

PMID- 24041445
TI  - Integrated approach to malaria prevention at household level in rural communities
      in Uganda: experiences from a pilot project.
AB  - BACKGROUND: Malaria is a major public health challenge in sub-Saharan Africa. In
      Uganda, malaria is the leading cause of morbidity and mortality especially among
      children under five years of age. This pilot project promoted prevention of
      malaria at household level using an integrated approach in two rural communities
      in Wakiso District, Uganda. This involved advocating and implementing several
      strategies in a holistic manner geared towards reduction in the occurrence of
      malaria. The specific strategies involved can be classified as: 1) personal
      protection - use of insecticide-treated bed nets and insecticide sprays; 2)
      reducing mosquito breeding sites - draining pools of water, larviciding and
      clearing unnecessary vegetation around homes; and 3) reducing entry of mosquitoes
      into houses - installing mosquito proofing in windows, ventilators and open
      eaves, and closing windows and doors early in the evenings. CASE DESCRIPTION: The
      objectives of the project were to: carry out a baseline survey on malaria
      prevention; train community health workers and increase awareness among the
      community on the integrated approach to malaria prevention; and, establish
      demonstration sites using the integrated approach. A baseline survey among 376
      households was conducted which generated information on the knowledge, attitudes
      and practices of the community in relation to malaria prevention. The project
      trained 25 community health workers and over 200 community members were
      sensitized on the integrated approach to malaria prevention. In addition, 40
      demonstration households using the integrated approach were established.
      DISCUSSION AND EVALUATION: The use of multiple methods in the prevention of
      malaria was appreciated by the community particularly the demonstration
      households using the integrated approach. Initial project evaluation showed that
      the community had become more knowledgeable about the various malaria prevention
      methods that were advocated in the integrated approach. In addition, some of the
      methods that were not being used before project implementation, such as early
      closing of windows, had been adopted. The presence of mosquitoes in the
      demonstration households had also reduced. CONCLUSION: The integrated approach to
      malaria prevention at household level was well perceived by the project
      community, which could be scaled up to other areas. More rigorous studies such as
      randomized controlled trials are also recommended to further explore the public
      health impact of the integrated approach to malaria prevention.

PMID- 24041444
TI  - Targeting and eradicating hepatic cancer cells with a cancer-specific vector
      carrying the Buforin II gene.
AB  - OBJECTIVE: The aim of this study was to investigate the suppressive effects of
      Buforin II on the growth of HepG2 cells. To accomplish this, we created a
      recombinant plasmid (pSUR-Buforin2) in which the survivin promoter was modified
      to drive the Buforin II gene. METHODS: The DNA fragment encoding the Buforin II
      gene was obtained by gene synthesis and cloned into the pSUR-Luc plasmid behind
      the survivin promoter. The vector was subsequently transfected into HepG2 and LO2
      cells. Cell proliferation was measured by the MTT assay, cell cytotoxicity
      detected by the LDH assay, and cell apoptosis determined by flow cytometry, DNA
      ladder assays, and immunoblot analysis. RESULTS: The pSUR-Buforin2 vector
      effectively suppressed the proliferation of HepG2 cells. The MTT and LDH assay
      demonstrated that under control of the survivin promoter, Buforin II was not
      expressed in LO2 cells, but it was expressed in tumor cells where cell death was
      also observed. AnnexinV-PI staining, DNA ladder assays, and western blots showed
      massive apoptosis in HepG2 cells transfected with pSUR-Buforin2. CONCLUSION: pSUR
      Buforin2 can significantly inhibit the growth of HepG2 cells, resulting in
      increased cancer cell apoptosis. Thus, this newly designed plasmid might provide
      a potent and selective anticancer therapy.

PMID- 24041446
TI  - [Public health competencies and contents in Spanish university degree programs of
      physical therapy, occupational therapy, environmental science, dentistry and
      veterinary science].
AB  - OBJECTIVE: To identify the basic competencies and contents related to public
      health to be included in degree programs according to the perspective of
      lecturers from various Spanish universities. METHOD: In the context of the Second
      Workshop on Public Health Contents in Degree Programs (Mahon, 19 to 20 September
      2012), 20 lecturers from different Spanish universities were distributed in five
      working groups. The lecturers had been selected from the instructional guides on
      public health and epidemiology published on the web sites of the Rectors'
      Conference of Spanish Universities. Each group worked on a degree program and the
      results were discussed in plenary sessions. RESULTS: The activities and
      competencies related to the three basic functions of public health were
      identified in all degree programs. Most of the professional competencies
      identified were related to the function of "assessment of population health
      needs". The contents proposed by the working groups related to epidemiology,
      basic concepts in public health, public health intervention, health management,
      and health policy. The main common topics among the degrees concerned the first
      three contents. CONCLUSIONS: Public health professional competencies and contents
      were identified in the degree programs examined. These results may serve as a
      starting point for a more detailed review of public health programs across degree
      levels and the search for a consensus on the common content that should be
      included in each of them.

PMID- 24041447
TI  - The complete mitochondrial genome of Ircinia sp. (Dictyoceratida: Irciniidae).
AB  - The mitochondrial genome of Ircinia sp. (Dictyoceratida: Irciniidae) is a
      circular molecule of 16,037 bp in length, containing 14 protein-coding genes, 2
      ribosomal RNA genes, 2 transfer RNA genes (trnW and trnM) and 13 non-coding
      segments. All genes are distributed in the same strand (H-strand). The overall
      base composition of the H-strand is as follows: T (37.84%), C (11.22%), A
      (24.81%), G (26.13%), with GC- and AT-skew of 0.399 and -0.208, respectively,
      reflecting unbalanced base composition between the two strands. The non-coding
      regions are 1190 bp in total length, with high AT content (76.31%). The current
      mitochondrial genome is identical to that of sibling species I. strobilina in
      gene order and contents, but differs from the latter in the presence of two kinds
      of repetitive sequences in the non-coding regions, of which one could form
      repetitive hairpin-forming elements.

PMID- 24041448
TI  - The whole mitochondrial genome of the Cynomolgus macaque (Macaca fascicularis).
AB  - Macaca fascicularis, known as the long-tailed macaque, is widely distributed in
      southern of East Asia and Southeast Asia. It was one of the most commonly used
      non-human primates in biomedical research. Thus, to illustrate the maternal
      phylogenetic status of M. fascicularis in primates based on the whole
      mitochondrial DNA (mtDNA) genome and determine a reference sequence for future
      population genetic studies by taking mtDNA as molecular marker, in this study,
      the high quality whole mtDNA genome of M. fascicularis was amplified and
      sequenced. Our data showed that the whole mtDNA genome of M. fascicularis
      includes 16,571 base pairs (bps). Further phylogenetic analyses of M.
      fascicularis were performed by incorporating the 83 available whole mtDNA genomes
      belonging to 77 primate species with Tupaia belangeri as out-group. Our result
      supported that M. fascicularis belongs to Macaca. Cercopithecinae.
      Cercopithecidae. Anthropoidea. Primates, which has the closest genetic affinity
      with Macaca mulatta. In addition, the ancestral divergence between the tarsier
      and other primate species was supported with evidence from the whole mtDNA
      genomes. 

PMID- 24041449
TI  - The complete mitochondrial genome of Xya japonica (Haan, 1842) (Orthoptera:
      Tridactyloidea).
AB  - The complete mitochondrial genome of Xya japonica (Haan, 1842), which was
      collected from Hebei province of China, is reported here. It is 15,352 bp in
      length and contains 71.2% AT. All X. japonica protein-coding sequences start with
      a typical ATN codon except for the cytochrome oxidase subunit I (cox1), which
      start with CCG. The usual termination codon TAA and TAG were found from 13
      protein-coding genes. All tRNA genes have the typical clover leaf structure,
      excluding trnS(AGN) that lacks the dihydrouracil arm. The sizes of the large and
      small ribosomal RNA genes are 1289 and 747 bp, respectively. The AT content of
      the A + T-rich region is 75.0%. The orientation and gene order of the X. japonica
      mitogenome is identical to Ellipes minuta and Gryllotalpa orientalis, there is no
      phenomenon of "DK rearrangement" which has been wide reported in Caelifera.

PMID- 24041450
TI  - Sequence variability in three mitochondrial genes among four roundworm species
      from wild animals in China.
AB  - Sequence variability in three mitochondrial DNA (mtDNA) regions, namely portions
      of cytochrome c oxidase subunit 1 (pcox1), NADH dehydrogenase subunit 1 (pnad1)
      and NADH dehydrogenase subunit 4 (pnad4), for Toxocara canis. Baylisacaris
      transfuga. Ascaris suum and Parascaris equorum from Canis lupus. Ursus
      thibetanus. Sus scrofa and Equus burchelli in China were examined. The lengths of
      the sequences of pcox1, pnad1 and pnad4 were 711 bp, 648 bp and 666 bp,
      respectively. No intra-species differences were detected in pcox1 for the four
      examined ascarid species, in pnad1 for T. canis. A. suum and P. equorum, and in
      pnad4 for B. transfuga and P. equorum. Sequence differences in pnad4 for six
      roundworm samples of T. canis and P. equorum were 0-0.1% and 0-0.3%,
      respectively, and were 0-0.3% in pnad1 for six roundworm samples isolate of B.
      transfuga. The inter-specific sequence differences among four species were 8.7
      12.4% for pcox1, 13.9-17.7% for pnad1, and 14.0-25.7% for pnad4. Phylogenetic
      analyses suggested that the three mtDNA fragments could be used to identify
      ascarid species in families Ascaridiae and Toxocaridae. 

PMID- 24041451
TI  - DNA barcoding of elasmobranchs from Indian coast and its reliability in
      delineating geographically widespread specimens.
AB  - Identification of elasmobranchs by conventional taxonomy is difficult due to
      similarities in morphological characters. Species-specific molecular markers are
      good choice for identifying species irrespective of it's life stage. Recently,
      mitochondrial cytochrome c oxidase subunit I (COI) gene got global recognition as
      a barcode gene to discriminate all animals up-to species level. In this study,
      mitochondrial COI partial gene was used to develop DNA barcodes for 18 species of
      elasmobranchs (10 species of sharks and 8 species of rays). The COI barcodes
      clearly distinguished all the species with high interspecific distance values
      than intraspecific values. The average interspecific and intraspecific distance
      values are 8.6% and 0.3% for sharks, respectively and 12.4% and 0.63% for rays,
      respectively using K2P method. The Neighbor-Joining tree showed distinct clusters
      shared by the species of same genera. The COI barcodes were also used to estimate
      allopatric divergences for selected species across broad geographical locations
      and found that Sphyrna lewini, Aetobatus narinari and Neotrygon kuhlii have
      cryptic diversity. 

PMID- 24041452
TI  - Perspectives on wellness self-monitoring tools for older adults.
AB  - PURPOSE: Our purpose was to understand different stakeholder perceptions about
      the use of self-monitoring tools, specifically in the area of older adults'
      personal wellness. In conjunction with the advent of personal health records,
      tracking personal health using self-monitoring technologies shows promising
      patient support opportunities. While clinicians' tools for monitoring of older
      adults have been explored, we know little about how older adults may self-monitor
      their wellness and health and how their health care providers would perceive such
      use. METHODS: We conducted three focus groups with health care providers (n=10)
      and four focus groups with community-dwelling older adults (n=31). RESULTS: Older
      adult participants' found the concept of self-monitoring unfamiliar and this
      influenced a narrowed interest in the use of wellness self-monitoring tools. On
      the other hand, health care provider participants showed open attitudes toward
      wellness monitoring tools for older adults and brainstormed about various
      stakeholders' use cases. The two participant groups showed diverging perceptions
      in terms of: perceived uses, stakeholder interests, information ownership and
      control, and sharing of wellness monitoring tools. CONCLUSIONS: Our paper
      provides implications and solutions for how older adults' wellness self
      monitoring tools can enhance patient-health care provider interaction, patient
      education, and improvement in overall wellness.

PMID- 24041453
TI  - Transitioning from a computerized provider order entry and paper documentation
      system to an electronic health record: expectations and experiences of hospital
      staff.
AB  - OBJECTIVES: To examine healthcare worker's perceptions, expectations, and
      experiences regarding how work processes, patient-related safety, and care were
      affected when a quaternary care center transitioned from one computerized
      provider order entry (CPOE) system to a full electronic health record (EHR).
      METHODS: The I-SEE survey was administered prior to and 1-year after transition
      in systems. The construct validity and reliability of the survey was assessed
      within the current population and also compared to previously published results.
      Pre- and 1-year post-implementation scale means were compared within and across
      time periods. RESULTS: The majority of respondents were nurses and personnel
      working in the acute care setting. Because a confirmatory factor analysis
      indicated a lack of fit of our data to the I-SEE survey's 5-factor structure, we
      conducted an exploratory factor analysis that resulted in a 7-factor structure
      which showed better reliability and validity. Mean scores for each factor
      indicated that attitudes and expectations were mostly positive and score trends
      over time were positive or neutral. Nurses generally had less positive attitudes
      about the transition than non-nursing respondents, although the difference
      diminished after implementation. CONCLUSIONS: Findings demonstrate that the
      majority of responding staff were generally positive about transitioning from
      CPOE system to a full electronic health record (EHR) and understood the goals of
      doing so, with overall improved ratings over time. In addition, the I-SEE survey,
      when modified based on our population, was useful for assessing patient care and
      safety related expectations and experiences during the transition from one CPOE
      system to an EHR.

PMID- 24041454
TI  - [Unknown intracerebral tumour presenting as brainstem compression following
      unintentional dural puncture].
AB  - A 36-year old primigravid of 41 weeks gestation was admitted to the labour ward.
      Her past medical history included hyperemesis gravidarum and migraine. An
      accidental dural puncture occurred during labour epidural analgesia. In the
      postpartum period she presented with continuous headache, and was treated with
      oral analgesics, oral caffeine, fluid therapy, and tetracosactide. She refused an
      epidural blood patch. On the seventh day postpartum, the patient was re-admitted
      to the Emergency Department with decreased level of consciousness and signs of
      brainstem compression. Cranial computed tomography and magnetic resonance imaging
      showed a posterior fossa tumour. An emergency craniotomy was performed with
      complete neurological recovery. This case emphasises the need to consider the
      differential diagnoses of post-dural puncture headache and to highlight the
      warning signs in patients who do not respond despite treatment with conventional
      therapy. 

PMID- 24041456
TI  - Hospitalized youth and child abuse: a systematic examination of psychiatric
      morbidity and clinical severity.
AB  - Many children and adolescents who require psychiatric hospitalization have been
      physically or sexually abused, yet the association between reported histories of
      abuse and the complexity and severity of mental illness among psychiatrically
      hospitalized youth is poorly described with regard to current inpatient
      psychiatric practice. We sought to determine the association between histories of
      abuse and psychiatric complexity and severity in psychiatrically hospitalized
      youth including comorbidity patterns, psychotropic medication use, reason for
      admission and length of hospitalization. A systematic chart review was performed
      on 1433 consecutive psychiatric hospitalizations of children and adolescents that
      occurred over a 10-month period. Children with a history of abuse were more
      likely to be diagnosed with multiple DSM-IV-TR disorders than non-traumatized
      children. A history of sexual abuse was associated with more medication use than
      in their non-traumatized peers and a higher likelihood of treatment with
      antipsychotic medications, both at admission and discharge. Physical and sexual
      abuse were independently associated with increased length of stays, with exposure
      to both physical and sexual abuse associated with a 2-day increase in duration of
      hospitalization compared to non-traumatized patients. The findings from this
      study draw attention to the adverse impact of abuse on psychiatric morbidity and
      complexity and suggest the need for trauma-informed treatment in psychiatric
      hospital settings. 

PMID- 24041455
TI  - Mediation effects of problem drinking and marijuana use on HIV sexual risk
      behaviors among childhood sexually abused South African heterosexual men.
AB  - HIV/AIDS prevalence in South Africa is one of the highest in the world with
      heterosexual, transmission predominantly promoting the epidemic. The goal of this
      study is to examine whether, marijuana use and problem drinking mediate the
      relationship between histories of childhood sexual, abuse (CSA) and HIV risk
      behaviors among heterosexual men. Participants were 1181 Black men aged, 18-45
      from randomly selected neighborhoods in Eastern Cape Province, South Africa.
      Audio computer assisted, self-interviewing was used to assess self-reported
      childhood sexual abuse, problem drinking, and marijuana (dagga) use, and HIV
      sexual transmission behavior with steady and casual partners. Data were analyzed
      using multiple meditational modeling. There was more support for problem,
      drinking than marijuana use as a mediator. Findings suggest that problem drinking
      and marijuana use, mediate HIV sexual risk behaviors in men with histories of
      CSA. Focusing on men with histories of CSA, and their use of marijuana and
      alcohol may be particularly useful for designing strategies to reduce, HIV sexual
      transmission in South Africa. 

PMID- 24041457
TI  - Phytosynergy in some Hypoxis species and pharmacological properties of a Hypoxis
      based phytopharmaceutical formula.
AB  - ETHNOPHARMACOLOGY RELEVANCE: Hypoxis species are used extensively in traditional
      medicine in southern Africa for several ailments including tuberculosis, chest
      infections, and nervous and urinary disorders. Several other claims have been
      made for extracts emanating from Hypoxis species and have led to the production
      of several commercial products used as immunostimulants mostly for people living
      with HIV/AIDS and cancer. This study was aimed at investigating the biological
      activity of four Hypoxis species and a commercial herbal product, 'African potato
      extract' (APE). MATERIALS AND METHODS: Antibacterial, antifungal, cyclooxygenase
      (COX) and acetylcholineasterase (AChE) inhibitory activities of four Hypoxis
      species (H. acuminata, H. colchicifolia, H. hemerocallidea and H. rigidula) and a
      popular Hypoxis-based herbal preparation, APE were tested. The phytoconstituents
      of the mixture were also profiled using TLC methods. Several combinations of the
      Hypoxis species were prepared and their synergism, additive, autonomic and
      antagonism effects investigated. As a quality control measure, batch to batch
      comparison in the phytoconstituents and biological activity of APE was carried
      out. RESULTS: The results confirmed H. colchicifolia and H. hemerocallidea as the
      phytoconstituents of APE. The extracts showed a broad spectrum of activities
      against the bacterial and fungal strains used. Of particular interest were the
      activities exhibited by the APE and combinations of H. colchicifolia and H.
      hemerocallidea. The APE mixture exhibited good antibacterial activity (MIC values
      of 0.78mg/ml each) in all the tested batches against the bacterial strains used.
      The water extracts of all four Hypoxis species, three batches of APE and the
      combination (water extracts) of H. colchicifolia and H. hemerocallidea exhibited
      high COX-1 and moderate COX-2 inhibitory activity except for H. acuminata which
      showed low activity against COX-2. All the extract, batches of APE and
      combinations showed low to moderate AChE inhibitory activity. These results
      provided some evidence of phytosynergy in some extracts of H. hemerocallidea and
      H. colchicifolia except for a few extracts which act as additive, autonomous and
      antagonistic when used to inhibit some bacterial and fungal strains. However,
      this was not the case for COX and AChE inhibition, as only acetone extracts acted
      in a synergistic way to reduce the activity of the enzyme. CONCLUSION: Even
      though the results give an indication of a positive interaction between some
      extracts of H. hemerocallidea and H. colchicifolia, the study was carried out on
      1:1 v/v combinations only. It is therefore important to carry out isobologram
      studies, which considers more than one ratio of the combinations.

PMID- 24041458
TI  - Neuroprotective effect of Liuwei Dihuang decoction on cognition deficits of
      diabetic encephalopathy in streptozotocin-induced diabetic rat.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Liuwei Dihuang decoction (LWDHD) is a well-known
      prescription of traditional Chinese medicine (TCM) and consists of six crude
      drugs including Rehmannia glutinosa Libosch. (family: Scrophulariaceae), Cornus
      officinalis Sieb. (family: Cornaceae), Dioscorea oppositifolia L. (family:
      Dioscoreaceae), Paoenia ostii (family: Paeoniaceae), Alisma orientale (G.
      Samuelsson) Juz (family: Alismataceae) and Poria cocos (Schw.) Wolf (family:
      Polyporaceae). It has been used for the treatment of "Kidney-Yin" deficiency
      syndrome in clinic in China for a long time. Recent studies found that LWDHD had
      a potential benefit for the treatment of diabetic complications. The aim of the
      present study is to investigate the neuroprotective effect of LWDHD on memory and
      cognition deficits in streptozotocin (STZ)-induced diabetic encephalopathy (DE)
      rats. MATERIALS AND METHODS: Adult male Sprague Dawley (SD) rats were fed with
      high-glucose-fat diet for 50 days and then received an intraperitoneal injection
      of STZ (40 mg/kg) to induce DE model. Morris water maze test was used to evaluate
      the memory and cognition capability of DE rats. Choline acetyltransferase (ChAT),
      acetylcholinesterase (AChE), Na(+)-K(+)-ATP enzyme, iNOS and GSH kits were used
      to determine their activities or content in hippocampus. TUNEL staining,
      immunohistochemistry and Congo red staining were conducted to evaluate the
      apoptosis, caspase-3 protein expression, insulin-like growth factors 1 (IGF-1)
      and brain derived neurophic factor (BDNF) expressions, as well as Abeta
      deposition. RESULTS: The treatment with LWDHD (1 and 2g/kg, p.o., once daily, 30
      days) could significantly reduce the escape latency time and path length, and
      obviously enhance the spent time in the target quadrant and platform crossings in
      Morris water maze test compared with model group (P<0.05, P<0.01). LWDHD could
      also significantly decrease the level of fasting blood glucose, increase Na(+)
      K(+)-ATP enzyme and ChAT activities, enhance remarkedly GSH level while decrease
      significantly AChE and iNOS activities in hippocampus (P<0.05, P<0.01).
      Furthermore, TUNEL staining, Congo red staining and immunohistochemistry showed
      that LWDHD significantly improved the expressions of IGF-1 and BDNF, attenuated
      the neural apoptosis, overexpression of caspase-3 and Abeta deposition in the
      hippocampus and cerebral cortex of STZ-induced DE rats (P<0.01). CONCLUSION: Our
      findings suggested that LWDHD had a neuroprotective effect on DE rats. LWDHD may
      be of benefit in the treatment of DE.

PMID- 24041459
TI  - Yeast exposure in the preparation of steamed rehmannia root improving its effects
      on alloxan-induced diabetic rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The root of Rehmannia glutinosa (Gaertn.) DC. has
      been used in China for more than 2000 years to treat various diseases including
      diabetes mellitus (DM) and its complications. Steamed rehmannia root (SRR) is one
      of the mainly used forms. During its preparation, the material has the chance to
      be exposed to microorganisms, particularly yeast. The aim of this study is to
      verify the effect of SRR on diabetes complications and the necessity of yeast
      exposure. MATERIALS AND METHODS: Water extract of SRR was incubated with alcohol
      yeast to obtain fermented SRR (FSRR). Alloxan-induced diabetic rats were
      administrated with medicated animal chows for 8 weeks. Urine volume, fasted blood
      glucose and food intake were monitored, and open field test and tail immersion
      test were conducted in the last week, plasma and urine samples were subjected to
      biochemical examinations. RESULTS: In DM rats, defecation in open field test was
      found reduced, and tail flick latency in tail immersion test increased. In the
      meantime, urinary excretions of Na(+), K(+), aldosterone, albumin and creatinine
      increased, and plasma concentrations of Na(+), K(+) and creatinine reduced and
      those of aldosterone, TXB2/6-Keto-PGF(1alpha) and urea nitrogen elevated. Most of
      these indicators were significantly improved by FSRR administration, but the
      effects of SRR were relatively inferior in several aspects. However, SRR and FSRR
      could not improve the typical symptoms of DM. CONCLUSIONS: Our data demonstrated
      that both SRR and FSRR have no obvious hypoglycemic effect, but have the
      potential to prevent the onset and development of diabetes complications, and
      this function can be improved by yeast exposure.

PMID- 24041461
TI  - Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: a
      possible role for SirT3 activation.
AB  - Berberine is an isoquinoline alkaloid with anti-diabetic properties. Despite the
      central role of liver and thus hepatic mitochondria in whole-body metabolism,
      berberine effects on hepatic mitochondrial function in an obesity model are still
      unknown. Here, we demonstrate that berberine treatment recovers mitochondrial
      efficiency when altered by a high-fat feeding. Mitochondria isolated from the
      liver of high-fat fed rats exhibited decreased capacity to accumulate calcium and
      impaired oxidative phosphorylation (OXPHOS) capacity, as shown by impaired
      mitochondrial membrane potential, oxygen consumption and cellular ATP levels.
      Interestingly, the recovery of mitochondrial function by berberine was associated
      with an increased activity of the mitochondrial sirtuin 3 (SirT3). In conclusion,
      berberine potent protective effects against metabolic syndrome may rely on
      increasing mitochondrial SirT3 activity, normalizing mitochondrial function and
      preventing a state of energetic deficit caused by impaired OXPHOS. 

PMID- 24041460
TI  - Management of diabetic complications: a chemical constituents based approach.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Long term hyperglycemia leads to development of
      complications associated with diabetes. Diabetic complications are now a global
      health problem without effective therapeutic approach. Hyperglycemia and
      oxidative stress are important components for the development of diabetic
      complications. Over the past few decades, herbal medicines have attracted much
      attention as potential therapeutic agents in the prevention and treatment of
      diabetic complications due to their multiple targets and less toxic side effects.
      This review aims to assess the current available knowledge of medicinal herbs for
      attenuation and management of diabetic complications and their underlying
      mechanisms. MATERIAL AND METHODS: Bibliographic investigation was carried out by
      scrutinizing classical text books and peer reviewed papers, consulting worldwide
      accepted scientific databases (SCOPUS, PUBMED, SCIELO, NISCAIR, Google Scholar)
      to retrieve available published literature. The inclusion criteria for the
      selection of plants were based upon all medicinal herbs and their active
      compounds with attributed potentials in relieving diabetic complications.
      Moreover, plants which have potential effect in ameliorating oxidative stress in
      diabetic animals have been included. RESULTS: Overall, 238 articles were reviewed
      for plant literature and out of the reviewed literature, 127 articles were
      selected for the study. Various medicinal plants/plant extracts containing
      flavonoids, alkaloids, phenolic compounds, terpenoids, saponins and phytosterol
      type chemical constituents were found to be effective in the management of
      diabetic complications. This effect might be attributed to amelioration of
      persistent hyperglycemia, oxidative stress and modulation of various metabolic
      pathways involved in the pathogenesis of diabetic complications. CONCLUSION:
      Screening chemical candidate from herbal medicine might be a promising approach
      for new drug discovery to treat the diabetic complications. There is still a dire
      need to explore the mechanism of action of various plant extracts and their
      toxicity profile and to determine their role in therapy of diabetic
      complications. Moreover, a perfect rodent model which completely mimics human
      diabetic complications should be developed.

PMID- 24041462
TI  - Advancing adolescent maternal development: a grounded theory.
AB  - OBJECTIVES: This paper reports a substantive grounded theory called the theory of
      Advancing Adolescent Maternal Development. DESIGN: A grounded theory approach was
      used. SAMPLE: Thirty public health nurses working with adolescent clients in a
      state public health nurse home visiting program volunteered to participate in
      this study. RESULTS: The basic social psychological problem that emerged from the
      data was incomplete and at risk adolescent maternal development. Social support
      and public health nursing interventions are central in the problem resolution
      process which occurs in stages. CONCLUSIONS: Study results can be used to inform
      the nursing care of pregnant and parenting adolescents.

PMID- 24041463
TI  - "My situation wasn't that unique": The experience of teens in abusive
      relationships.
AB  - College freshman and sophomores with histories of high school dating violence
      were invited to participate in a study about that experience. The shared
      experience described by ten participants was that of being controlled. Control is
      established by creating a sense of responsibility and is maintained by angry
      outburst, threats to self, and guilt. Participants described an expectation of
      constant contact that included techno vigilance. In their stories, young women
      miss good and better times, hope for "the ideal romance," and continue to care
      and have concern for their abuser who is described as "troubled."

PMID- 24041464
TI  - The physiological roles of primary phospholipase C.
AB  - The roles of phosphoinositide-specific phospholipase C (PLC) have been
      extensively investigated in diverse cell lines and pathological conditions. Among
      the PLC isozmes, primary PLCs, PLC-beta and PLC-gamma, are directly activated by
      receptor activation, unlike other secondary PLCs (PLC-E, PLC-delta1, and PLC
      eta1). PLC-beta isozymes are activated by G protein couple receptor and PLC-gamma
      isozymes are activated by receptor tyrosine kinase (RTK). Primary PLCs are
      differentially expressed in different tissues, suggesting their specific roles in
      diverse tissues and regulate a variety of physiological and pathophysiological
      functions. Thus, dysregulation of phospholipases contributes to a number of human
      diseases and primary PLCs have been identified as therapeutic targets for
      prevention and treatment of diseases. Here we review the roles of primary PLCs in
      physiology and their impact in pathology. 

PMID- 24041465
TI  - High vancomycin minimum inhibitory concentrations with heteroresistant vancomycin
      intermediate Staphylococcus aureus in meticillin-resistant S. aureus bacteraemia
      patients.
AB  - Patients with high vancomycin minimum inhibitory concentrations (MICs) and
      heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) infection
      are associated with treatment failure and poor outcomes. The main purpose of this
      study was to investigate the effect of hVISA on patient outcome, considering both
      the high vancomycin MIC and the existence of heteroresistant phenotypes. From
      January 2005 to December 2009, consecutive meticillin-resistant S. aureus (MRSA)
      isolates from 284 cases of MRSA bacteraemia receiving glycopeptide therapy were
      collected for further MIC and hVISA testing. The demographic distribution,
      clinical features and outcomes in bacteraemia patients with different vancomycin
      MICs and hVISA status in MRSA isolates were subsequently compared. Subjects were
      divided into three groups: low vancomycin MIC (<1.5mg/L) with vancomycin
      sensitive S. aureus (VSSA) (n=50); high vancomycin MIC (>=1.5mg/L) with VSSA
      (n=218); and high vancomycin MIC with hVISA (n=16). Cox regression analysis
      demonstrated that the high MIC with VSSA group exhibited significantly higher 30
      day mortality than the low MIC with VSSA group [odds ratio (OR)=2.349, 95%
      confidence interval (CI) 1.078-5.118]. The high MIC with hVISA phenotype was not
      associated with higher mortality but was independently associated with persistent
      MRSA bacteraemia (OR=5.996, 95% CI 1.438-25.005). To summarise, although hVISA is
      correlated with persistent bacteraemia, higher mortality in high vancomycin MIC
      infections could not be explained by the existing hVISA phenotype. Facing
      persistent bacteraemia under glycopeptide therapy for 7 days, clinicians should
      consider shifting to an alternative class of antibiotics to treat hVISA
      infection. 

PMID- 24041466
TI  - Ampicillin/sulbactam: its potential use in treating infections in critically ill
      patients.
AB  - The purpose of this paper was to review the potential utility of
      ampicillin/sulbactam (SAM) as a therapy for serious infections in critically ill
      patients. Data for this review were identified by searches of PubMed and of the
      reference lists of the included articles. We found that SAM appears to have a
      number of characteristics that support its use in the treatment of serious
      infections in critically ill patients. SAM demonstrates extensive penetration
      into many infection sites, supporting its use in a wide range of infection types.
      Microbiologically, sulbactam has strong intrinsic antibiotic activity against
      multidrug-resistant (MDR) bacteria, including Acinetobacter baumannii, which
      supports its use for the treatment of infections mediated by this pathogen. Of
      some concern, there have been reports showing a decline in susceptibility of some
      bacteria to SAM. As such, use of lower doses (4/2g/day), particularly for MDR A.
      baumannii, has been linked with a 30% reduced success rate in critically ill
      patients. The therapeutic challenges for ensuring achievement of optimal dosing
      of SAM result partly from bacterial susceptibility but also from the
      pharmacokinetic (PK) alterations common to beta-lactam agents in critical
      illness. These PK changes are likely to reduce the ability of standard dosing to
      achieve the concentrations observed in non-critically ill patients. Optimisation
      of therapy may be more likely with the use of higher doses, administration by 4h
      infusion or by combination therapy, particularly for the treatment of infections
      caused by MDR pathogens. 

PMID- 24041467
TI  - Stride length asymmetry in split-belt locomotion.
AB  - The number of studies utilizing a split-belt treadmill is rapidly increasing in
      recent years. This has led to some confusion regarding the definitions of
      reported gait parameters. The purpose of this paper is to clearly present the
      definitions of the gait parameters that are commonly used in split-belt treadmill
      studies. We argue that the modified version of stride length for split-belt gait,
      which is different from the standard definition of stride length and actually is
      a measure of limb excursion, should be referred to as 'limb excursion' in future
      studies. Furthermore, the symmetry of stride length and stride time is
      specifically addressed. 

PMID- 24041468
TI  - Automated event detection algorithms in pathological gait.
AB  - Accurate automated event detection is important in increasing the efficiency and
      utility of instrumented gait analysis. Published automated event detection
      algorithms, however, have had limited testing on pathological populations,
      particularly those where force measurements are not available or reliable. In
      this study we first postulated robust definitions of gait events that were
      subsequently used to compare kinematic based event detection algorithms across
      difficult pathologies. We hypothesized that algorithm accuracy would vary by gait
      pattern, and that accurate event detection could be accomplished by first
      visually classifying the gait pattern, and subsequently choosing the most
      appropriate algorithm. Nine published kinematic event detection algorithms were
      applied to an existing instrumented pediatric gait database (primarily cerebral
      palsy pathologies), that were categorized into 4 visually distinct gait patterns.
      More than 750 total events were manually rated and these events were used as a
      gold standard for comparison to each algorithm. Results suggested that for foot
      strike events, algorithm choice was dependent on whether the foot's motion in
      terminal swing was more horizontal or vertical. For horizontal foot motion in
      swing, algorithms that used horizontal position, resultant sagittal plane
      velocity, or horizontal acceleration signals were most robust; while for vertical
      foot motion, resultant sagittal velocity or vertical acceleration excelled. For
      toe off events, horizontal position or resultant sagittal plane velocity
      performed the best across all groups. We also tuned the resultant sagittal plane
      velocity signal to walking speed to create an algorithm that can be used for all
      groups and in real time. 

PMID- 24041469
TI  - Characteristics of Nigerian women taking sulfadoxine/pyrimethamine twice during
      pregnancy for the prevention of malaria.
AB  - OBJECTIVE: To investigate the characteristics of women in Nigeria who are likely
      to take sulfadoxine/pyrimethamine (SP) as recommended for the prevention of
      malaria in pregnancy to reduce maternal and child mortality rates. METHODS: A
      cross-sectional survey of 1380 women was conducted using a structured
      questionnaire. The women had given birth within 6months prior to the survey and
      were drawn from 6 local government areas in Nigeria. RESULTS: Several demographic
      factors-older age bracket, ever attended school, currently living with a partner,
      ever married, and wealth-were significantly associated with compliance.
      Compliance was higher among respondents who had ever been married than among
      those who had never been married (chi(2)=6.733; P=0.006). Compliance was also
      higher among those in paid employment (chi(2)=17.110; P<0.001) and those in a
      higher wealth quintile (chi(2)=34.861; P<0.001). Knowledge of malaria, which
      included prevention of malaria in pregnancy through use of IPTp with 2 doses of
      SP, showed a positive association with compliance. Compliance with 2 doses of SP
      among those with good knowledge was higher (63.9%) than among those with poor
      knowledge (46.9%) (chi(2)=26.981; P<0.001). CONCLUSION: The present findings
      could help in targeting health education programs to specific subgroups of women
      to increase compliance with the recommended 2 doses of SP for the prevention of
      malaria in pregnancy.

PMID- 24041470
TI  - Integrative genomic and functional profiling of the pancreatic cancer genome.
AB  - BACKGROUND: Pancreatic cancer is a deadly disease with a five-year survival of
      less than 5%. A better understanding of the underlying biology may suggest novel
      therapeutic targets. Recent surveys of the pancreatic cancer genome have
      uncovered numerous new alterations; yet systematic functional characterization of
      candidate cancer genes has lagged behind. To address this challenge, here we have
      devised a highly-parallel RNA interference-based functional screen to evaluate
      many genomically-nominated candidate pancreatic cancer genes simultaneously.
      RESULTS: For 185 candidate pancreatic cancer genes, selected from recurrently
      altered genomic loci, we performed a pooled shRNA library screen of cell
      growth/viability across 10 different cell lines. Knockdown-associated effects on
      cell growth were assessed by enrichment or depletion of shRNA hairpins, by
      hybridization to barcode microarrays. A novel analytical approach (COrrelated
      Phenotypes for On-Target Effects; COPOTE) was used to discern probable on-target
      knockdown, based on identifying different shRNAs targeting the same gene and
      displaying concordant phenotypes across cell lines. Knockdown data were
      integrated with genomic architecture and gene-expression profiles, and selected
      findings validated using individual shRNAs and/or independent siRNAs. The pooled
      shRNA library design delivered reproducible data. In all, COPOTE analysis
      identified 52 probable on-target gene-knockdowns. Knockdown of known oncogenes
      (KRAS, MYC, SMURF1 and CCNE1) and a tumor suppressor (CDKN2A) showed the expected
      contrasting effects on cell growth. In addition, the screen corroborated
      purported roles of PLEKHG2 and MED29 as 19q13 amplicon drivers. Most notably, the
      analysis also revealed novel possible oncogenic functions of nucleoporin NUP153
      (ostensibly by modulating TGFbeta signaling) and Kruppel-like transcription
      factor KLF5 in pancreatic cancer. CONCLUSIONS: By integrating physical and
      functional genomic data, we were able to simultaneously evaluate many candidate
      pancreatic cancer genes. Our findings uncover new facets of pancreatic cancer
      biology, with possible therapeutic implications. More broadly, our study provides
      a general strategy for the efficient characterization of candidate genes emerging
      from cancer genome studies.

PMID- 24041471
TI  - Genetic diversity and molecular evolution of the major human metapneumovirus
      surface glycoproteins over a decade.
AB  - BACKGROUND: Human metapneumovirus (HMPV) is a recently discovered paramyxovirus
      that is a major cause of respiratory infections worldwide. OBJECTIVES: We aim to
      describe the molecular evolution of the HMPV F (fusion) and G (attachment)
      surface glycoproteins because they are targets for vaccines, monoclonal
      antibodies and antivirals currently in development. STUDY SETTING: Nasopharyngeal
      aspirates were collected in children <3 years old with acute respiratory
      infection in Quebec City during 2001-2010. HMPV-positive samples (n = 163)
      underwent HMPV-F and -G gene sequencing. Furthermore, HMPV-F (n = 124) and -G (n
      = 217) sequences were obtained from GenBank and other studies. Evolutionary
      analyses (phylogenetic reconstruction, sequence identity, detection of
      recombination and adaptive evolution) were computed. RESULTS: Sequences clustered
      into 5 genetic lineages (A1, A2a, A2b, B1 and B2). Multiple lineages circulated
      each year in Quebec City. With the exception of B1, each of the 5 subgroups was
      the predominant lineage during >=1 season. The A1 lineage was not detected since
      2002-2003 in our local cohort. There was no evidence of inter- or intragenic
      recombination. HMPV-F was highly conserved, whereas HMPV-G exhibited greater
      diversity. HMPV-F demonstrated strong evidence of purifying selection, both
      overall and in an abundance of negatively selected amino acid sites. In contrast,
      sites under diversifying selection were detected in all HMPV-G lineages (range, 4
      15), all of which were located in the ectodomain. CONCLUSIONS: Predominant
      circulating HMPV lineages vary by year. HMPV-F is highly constrained and
      undergoes significant purifying selection. Given its high genetic variability, we
      found a modest number of positively selected sites in HMPV-G.

PMID- 24041472
TI  - Detection limit of architect hepatitis C core antigen assay in correlation with
      HCV RNA, and renewed confirmation algorithm for reactive anti-HCV samples.
AB  - BACKGROUND: hepatitis C infections are detected by anti-HCV screening tests.
      Reactive anti-HCV results give no information about the presence or absence of
      hepatitis C viruses, or of unspecific reactivity. To obtain information about the
      viral load, HCV RNA measurements, following a reactive anti-HCV result, are
      performed in well equipped and specialised laboratories. Anti-HCV immunoblots are
      the only means to exclude non specific reactivity. The measurement of HCV core
      antigen (HCV-Ag), as an alternative to HCV RNA, is discussed, as it can be
      analysed on the same instrument as anti-HCV. OBJECTIVES: The detection limit of
      HCV-Ag is crucial to use it in lieu of HCV RNA, in regard of the different
      genotypes. A renewed algorithm is proposed to exclude unspecific reactivity of
      anti-HCV. STUDY DESIGNS: Samples were tested on Architect i2000SR (Abbott) for
      anti-HCV and HCV-Ag. HCV RNA measurements were obtained by Cobas Ampliprep/Taqman
      (Roche) or m2000rt((r)) (Abbott). RESULTS AND CONCLUSIONS: Comparison between HCV
      Ag and HCV RNA from 126 samples of 101 patients with chronic hepatitis C gave
      linear regression R(2) 0.89, slope 0.885 and intercept -2.258, which were
      independent of the genotypes. The detection limit of HCV-Ag was between 2.4 and
      4.5 Log(10)IU/mL. A renewed algorithm for confirmation of reactive anti-HCV
      results is proposed: active or resolved hepatitis C infections or false
      reactivity can be differentiated by sequenced reflex testing due to HCV-Ag, anti
      HCV immunoblot and HCV RNA.

PMID- 24041473
TI  - Mathematical models: a key to understanding HIV envelope interactions?
AB  - The spikes of the human immunodeficiency virus (HIV) mediate viral entry and are
      the most important targets for neutralizing antibodies. Each spike consists of
      three identical subunits. The role of the spike's subunits in antibody binding is
      not fully understood. One experimental approach to analyze trimer function uses
      assays with mixed envelope trimer expressing cells or viruses. As these
      experiments do not allow direct observation of subunit functions, mathematical
      models are required to interpret them. Here we describe a modeling framework to
      study (i) the interaction of the V1V2 loop with epitopes on the V3 loop and (ii)
      the composition of quaternary epitopes. In a first step we identify which trimers
      can form in these assays and how they function under antibody binding. We then
      derive the behavior of an average trimer. We contrast two experimental reporting
      systems and list their advantages and disadvantages. In these experiments trimer
      formation might not be perfectly random and we show how these effects can be
      tested. As we still lack a potent vaccine against HIV, and this vaccine surely
      has to stimulate the production of neutralizing antibodies, mixed trimer
      approaches in combination with mathematical models will help to identify
      vulnerable sites of the HIV spike. 

PMID- 24041474
TI  - Isolation of HIV-1-reactive antibodies using cell surface-expressed
      gp160Deltac(BaL.).
AB  - Significant efforts have been made to identify HIV-1 neutralizing antibodies
      because they are considered to be critical to the design of an effective HIV-1
      vaccine. Although soluble HIV-1 envelope proteins can be used for this purpose,
      these reagents differ from membrane-anchored HIV-1 envelope spike in a number of
      important ways and display only a subset of its native epitopes. Consistent with
      this, some broadly neutralizing antibodies preferentially bind cell surface
      expressed HIV-1 envelope, but not the soluble protein. Here we report the details
      of a new method for isolating anti-HIV-1 specific B cells based on capturing
      cells that produce antibodies to cell surface-expressed gp160Deltac(BaL). While
      this method is far less efficient than sorting with soluble envelope proteins, it
      isolated broadly neutralizing anti-HIV-1 antibodies that bind cell surface
      expressed gp160Deltac(BaL) but not soluble envelope proteins. 

PMID- 24041475
TI  - Alzheimer disease: from biomarkers to diagnosis.
AB  - The discovery of biomarkers, considered as surrogate markers of the underlying
      pathological changes, led an international work group (IWG) to propose a new
      conceptual framework for AD in 2007 Dubois et al. (2007). According to the IWG,
      AD is now defined as a dual clinico-biological entity that can be recognized in
      vivo, prior to the onset of the dementia syndrome, on the basis of: i) a specific
      core clinical phenotype comprised of an amnestic syndrome of the hippocampal type
      and ii) supportive evidence from biomarkers reflecting the location or the nature
      of Alzheimer-type changes. Therefore, AD is diagnosed with the same criteria
      throughout all symptomatic phases of the disease based on the biologically-based
      approach to diagnosis independent of clinical expression of disease severity. The
      definitions were further clarified in 2010 (Dubois et al., 2010). Although the
      new criteria are proposed for research purposes, we encourage expert centres with
      adequate resources to begin to use the proposed algorithm in order to move the
      field forward and facilitate translation into clinical practice. 

PMID- 24041477
TI  - [Expert consensus on the detection and clinical management of familial
      hypercholesterolemia].
AB  - Familial hypercholesterolemia (FH) is one of the most common and severe genetic
      diseases, causing disabilities and premature death to those who suffer it. Lipid
      lowering therapy substantially improves the prognosis of FH patients and,
      therefore, appropriate pharmacological treatment is of the utmost importance. The
      Spanish Society of Arteriosclerosis (SEA) has always been a pioneer in the
      diagnosis and treatment of FH. Since its inception, FH has been one of the main
      areas of clinical and scientific interest, mainly for Lipids Units of the SEA,
      where most patients with this pathology are referred in Spain. This document
      arises from the willingness of our society to update the scientific knowledge on
      this subject and to provide physicians with clear clinical guidelines regarding
      diagnosis and treatment of FH. These guidelines can be summarized in two main
      aspects: early diagnosis of the disease and a rapid normalization of
      LDLcholesterol. In the coming years, health providers should accomplish that the
      majority of patients with FH are aware of their diagnosis and that adequate
      treatment is provided. 

PMID- 24041476
TI  - [Achievement of low-density lipoprotein cholesterol therapeutic goal in lipid and
      vascular risk units of the Spanish Arteriosclerosis Society].
AB  - OBJECTIVE: To evaluate low-density lipoprotein-cholesterol (LDLc) goal
      achievement among dyslipidemic patients treated in lipid and vascular risk units
      of the Spanish Society of Arteriosclerosis (SEA). The LDLc goal was based on the
      2007 European guidelines for cardiovascular prevention. DESIGN: Observational,
      longitudinal, retrospective, multicenter national study that included consecutive
      patients of both sexes over 18 years of age referred for dyslipidemia and
      cardiovascular risk. Information was collected from medical records corresponding
      to two visits in the lipid unit. RESULTS: We included 1,828 patients from 43
      lipid units. In the initial visit, 846 (46.3%) patients were on lipid lowering
      drug treatment. On the follow-up there was a significant increase in the use of
      cholesterol-lowering agents, except for a decrease in the use of nicotinic acid.
      65.3% of patients with vascular disease and 50.4% with diabetes achieved an LDLc
      level <100mg/dL. Overall, 44.7% of patients achieved the LDLc goal and the
      predictors in the multivariate analysis were age, waist circumference, diabetes
      and the presence of vascular disease. CONCLUSION: Dyslipidemic patients referred
      to SEA lipid units have improved LDLc goal achievement after follow-up compared
      with data reported from previous studies in other health care settings. This
      improvement was associated with a substantial increase in the prescription of
      statins, both in monotherapy and combined with ezetimibe. There is still a wide
      room for improvement in the effectiveness of hypercholesterolemia treatment.

PMID- 24041478
TI  - GESFIDE-PROPELLER approach for simultaneous R2 and R2* measurements in the
      abdomen.
AB  - PURPOSE: To investigate the feasibility of combining GESFIDE with PROPELLER
      sampling approaches for simultaneous abdominal R2 and R2* mapping. MATERIALS AND
      METHODS: R2 and R2* measurements were performed in 9 healthy volunteers and
      phantoms using the GESFIDE-PROPELLER and the conventional Cartesian-sampling
      GESFIDE approaches. RESULTS: Images acquired with the GESFIDE-PROPELLER sequence
      effectively mitigated the respiratory motion artifacts, which were clearly
      evident in the images acquired using the conventional GESFIDE approach. There was
      no significant difference between GESFIDE-PROPELLER and reference MGRE R2*
      measurements (p=0.162) whereas the Cartesian-sampling based GESFIDE methods
      significantly overestimated R2* values compared to MGRE measurements (p<0.001).
      CONCLUSION: The GESFIDE-PROPELLER sequence provided high quality images and
      accurate abdominal R2 and R2* maps while avoiding the motion artifacts common to
      the conventional Cartesian-sampling GESFIDE approaches.

PMID- 24041480
TI  - Detecting brain structural changes as biomarker from magnetic resonance images
      using a local feature based SVM approach.
AB  - Detecting brain structural changes from magnetic resonance (MR) images can
      facilitate early diagnosis and treatment of neurological and psychiatric
      diseases. Many existing methods require an accurate deformation registration,
      which is difficult to achieve and therefore prevents them from obtaining high
      accuracy. We develop a novel local feature based support vector machine (SVM)
      approach to detect brain structural changes as potential biomarkers. This
      approach does not require deformation registration and thus is less influenced by
      artifacts such as image distortion. We represent the anatomical structures based
      on scale invariant feature transform (SIFT). Likelihood scores calculated using
      feature-based morphometry is used as the criterion to categorize image features
      into three classes (healthy, patient and noise). Regional SVMs are trained to
      classify the three types of image features in different brain regions. Only
      healthy and patient features are used to predict the disease status of new brain
      images. An ensemble classifier is built from the regional SVMs to obtain better
      prediction accuracy. We apply this approach to 3D MR images of Alzheimer's
      disease, Parkinson's disease and bipolar disorder. The classification accuracy
      ranges between 70% and 87%. The highly predictive disease-related regions, which
      represent significant anatomical differences between the healthy and diseased,
      are shown in heat maps. The common and disease-specific brain regions are
      identified by comparing the highly predictive regions in each disease. All of the
      top-ranked regions are supported by literature. Thus, this approach will be a
      promising tool for assisting automatic diagnosis and advancing mechanism studies
      of neurological and psychiatric diseases. 

PMID- 24041479
TI  - An Internet-based intervention to promote mental fitness for mildly depressed
      adults: randomized controlled trial.
AB  - BACKGROUND: Depression is a worldwide problem warranting global solutions to
      tackle it. Enhancing well-being has benefits in its own right and could be a good
      strategy for preventing depression. Providing well-being interventions via the
      Internet may have synergetic effects. OBJECTIVE: Psyfit ("mental fitness online")
      is a fully automated self-help intervention to improve well-being based on
      positive psychology. This study examines the clinical effects of this
      intervention. METHODS: We conducted a 2-armed randomized controlled trial that
      compared the effects of access to Psyfit for 2 months (n=143) to a waiting-list
      control condition (n=141). Mild to moderately depressed adults in the general
      population seeking self-help were recruited. Primary outcome was well-being
      measured by Mental Health Continuum-Short Form (MHC-SF) and WHO Well-being Index
      (WHO-5); secondary outcomes were depressive symptoms, anxiety, vitality, and
      general health measured by Center for Epidemiological Studies Depression Scale
      (CES-D), Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A), and
      Medical Outcomes Study-Short Form (MOS-SF) vitality and general health subscales,
      respectively. Online measurements were taken at baseline, 2 months, and 6 months
      after baseline. RESULTS: The dropout rate was 37.8% in the Psyfit group and 22.7%
      in the control group. At 2-month follow-up, Psyfit tended to be more effective in
      enhancing well-being (nonsignificantly for MHC-SF: Cohen's d=0.27, P=.06;
      significantly for WHO-5: Cohen's d=0.31, P=.01), compared to the waiting-list
      control group. For the secondary outcomes, small but significant effects were
      found for general health (Cohen's d=0.14, P=.01), vitality (d=0.22, P=.02),
      anxiety symptoms (Cohen's d=0.32, P=.001), and depressive symptoms (Cohen's
      d=0.36, P=.02). At 6-month follow-up, there were no significant effects on well
      being (MHC-SF: Cohen's d=0.01, P=.90; WHO-5: Cohen's d=0.26, P=.11), whereas
      depressive symptoms (Cohen's d=0.35, P=.02) and anxiety symptoms (Cohen's d=0.35,
      P=.001) were still significantly reduced compared to the control group. There was
      no clear dose-response relationship between adherence and effectiveness, although
      some significant differences appeared across most outcomes in favor of those
      completing at least 1 lesson in the intervention. CONCLUSIONS: This study shows
      that an online well-being intervention can effectively enhance well-being (at
      least in the short-term and for 1 well-being measure) and can help to reduce
      anxiety and depression symptoms. Further research should focus on increasing
      adherence and motivation, reaching and serving lower-educated people, and
      widening the target group to include people with different levels of depressive
      symptoms. TRIAL REGISTRATION: Netherlands Trial Register (NTR) number: NTR2126;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2126 (archived by
      WebCite at http://www.webcitation.org/6IIiVrLcO).

PMID- 24041481
TI  - Wilderness medicine and working knowledge.

PMID- 24041482
TI  - Artificial sweeteners as potential tracers of municipal landfill leachate.
AB  - Artificial sweeteners are gaining acceptance as tracers of human wastewater in
      the environment. The 3 artificial sweeteners analyzed in this study were detected
      in leachate or leachate-impacted groundwater at levels comparable to those of
      untreated wastewater at 14 of 15 municipal landfill sites tested, including
      several closed for >50 years. Saccharin was the dominant sweetener in old (pre
      1990) landfills, while newer landfills were dominated by saccharin and acesulfame
      (introduced 2 decades ago; dominant in wastewater). Cyclamate was also detected,
      but less frequently. A case study at one site illustrates the use of artificial
      sweeteners to identify a landfill-impacted groundwater plume discharging to a
      stream. The study results suggest that artificial sweeteners can be useful
      tracers for current and legacy landfill contamination, with relative abundances
      of the sweeteners potentially providing diagnostic ability to distinguish
      different landfills or landfill cells, including crude age-dating, and to
      distinguish landfill and wastewater sources. 

PMID- 24041483
TI  - Occurrence, characteristics and leakage of polybrominated diphenyl ethers in
      leachate from municipal solid waste landfills in China.
AB  - Raw leachate samples were collected from various municipal solid waste (MSW)
      landfills in a densely populated city in North China to measure the levels and
      compositional patterns of polybrominated diphenyl ethers (PBDEs) in leachate. The
      total concentration of PBDEs ranged from 4.0 to 351.2 ng/L, with an average of
      73.0 ng/L. BDE-209 dominated the congeners in most of the samples, followed by
      BDE-47 and -99. Higher PBDEs concentrations were found in leachate from younger
      landfill facilities in the urban area. Pearson correlation analysis implied a
      potential dependence of the PBDEs level on landfill age, suspended solids and
      dissolved organic carbon, while the results of principal component analysis (PCA)
      suggested potential origins and transportation of PBDEs in leachate. The Monte
      Carlo method was adopted to estimate the annual leakage of PBDEs into the
      underground environment nationwide, based on two main scenarios: simple landfills
      with inadequate liner systems and composite-lined landfills with defective
      geomembranes. 

PMID- 24041484
TI  - Clinical, serological, and parasitological analysis of snakes naturally infected
      with Cryptosporidium serpentis.
AB  - Infection by Cryptosporidium serpentis is one of the most important diseases in
      reptiles and is characterized by chronic clinical or subclinical infection and
      the presence of hypertrophic gastritis, food regurgitation, progressive weight
      loss, mortality, and intermittent or continuous shedding of oocysts in the feces.
      The objectives of this study were to standardize an indirect enzyme-linked
      immunosorbent assay (ELISA) to detect antibodies against C. serpentis and to
      evaluate the clinical, parasitological, and humoral immune response in snakes
      naturally infected with C. serpentis. Twenty-one snakes naturally infected with
      C. serpentis and housed at the Butantan Institute, Sao Paulo, Brazil, underwent
      clinical and parasitological analyses for C. serpentis infection through daily
      records of clinical signs and a monthly survey of fecal shedding of oocysts using
      the Kinyoun's acid-fast staining. The serological evaluation was performed
      monthly by indirect ELISA using crude total antigen from oocysts of C. serpentis
      to detect anti-C. serpentis antibodies. Clinical symptoms consisted of food
      regurgitation, inappetence, and progressive weight loss. The parasitological
      analysis revealed intermittent fecal shedding of a variable number of oocysts in
      all snakes, with positivity in 85.32% (157/184) of the samples. The indirect
      ELISA was positive in 68.25% (86/126) of the samples. A humoral immune response
      was observed in most animals; however, fluctuating antibodies levels, leading to
      alternating positive and negative results, were observed in most snakes. 

PMID- 24041485
TI  - Isolation and RFLP genotyping of Toxoplasma gondii from the domestic dogs (Canis
      familiaris) from Grenada, West Indies revealed high genetic variability.
AB  - Stray dogs are considered as sentinels in the epidemiology of Toxoplasma gondii
      because they are carnivores and eat a variety of foods, including garbage. In the
      present study, tissues and sera of 249 stray dogs (Canis familiaris) from
      Grenada, West Indies were examined for T. gondii infection. Sera were examined
      for antibodies to T. gondii by the modified agglutination test (MAT); 89 (35.7%)
      of 249 were seropositive with titers of 25 in seven dogs, 50 in 22 dogs, 100 in
      22 dogs, 200 or higher in 38 dogs. Hearts of 76 seropositive dogs were bioassayed
      in mice. Viable T. gondii was isolated from 12 dogs; these isolates were
      designated TgDogGr1 to TgDogGr12. These isolates were further propagated in cell
      culture and DNA isolated from cell culture derived tachyzoites of 12 isolates was
      genotyped using 10 PCR-restriction fragment length polymorphism markers (SAG1,
      SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico). The results revealed
      six genotypes, including ToxoDB PCR-RFLP #1, #2, #3, #7, #13 and #224, with 1, 6,
      1, 2, 1 and 1 isolates, respectively. The result supports previous findings that
      T. gondii population genetics is highly diverse in Grenada.

PMID- 24041486
TI  - Quails are resistant to infection with Neospora caninum tachyzoites.
AB  - The aim of this study was to characterize the role of quails (Coturnix coturnix
      japonica) as intermediate hosts for Neospora caninum. Fifty-eight 20-day old
      quails were individually identified with numbered rings and kept in cages
      adequate for the species. The birds were fed commercial feed and distilled water
      ad libitum. They were weighed daily during the first month and every seven days
      from then on. The birds were randomly distributed into 3 groups; 40 quails (group
      A) and 8 quails (group B) received 3.5*10(6) and 5*10(6) N. caninum tachyzoites,
      respectively, and 10 quails (group C) received placebo. Four quails from group A
      and one from group C had their blood collected and were euthanized on the 1st,
      3rd, 5th, 7th, 14th, 21th, 30th, 60th, 120th day after infection (DAI), and 4
      quails from group B were euthanized on days 60th and 120th DAI. Following
      euthanasia, the birds were submitted to necropsy, the organs were weighed and
      fragments were collected for histopathology, immunohistochemistry (IHC) and PCR.
      On the 60th DAI, two dogs were fed tissue obtained from group A quails, and one
      dog was fed quail tissues from group B. The dogs' blood was collected weekly for
      serology, and their feces were collected daily for 33 days for microscopy and
      molecular identification of oocysts. Student's t-test was used to compare the
      weights of the collected organs and the quail and cloacal temperature. No quail
      presented any clinical signs or died. Splenomegaly and hepatomegaly were the
      primary necropsy findings during the first week of infection (p<0.05). Positive
      serology, immunoreactivity through IHC and molecular identification of the
      parasite, were observed, especially during the first two weeks of infection. No
      dogs eliminated the oocysts or seroconverted. The infected quails gained more
      weight than the control quails. The results demonstrated that quails are
      resistant to infection with N. caninum tachyzoites under the conditions of this
      study.

PMID- 24041488
TI  - The complexity of DNA double strand breaks is a critical factor enhancing end
      resection.
AB  - DNA double strand breaks (DSBs) induced by ionizing radiation (IR) are
      deleterious damages. Two major pathways repair DSBs in human cells, DNA non
      homologous end-joining (NHEJ) and homologous recombination (HR). It has been
      suggested that the balance between the two repair pathways varies depending on
      the chromatin structure surrounding the damage site and/or the complexity of
      damage at the DNA break ends. Heavy ion radiation is known to induce complex-type
      DSBs, and the efficiency of NHEJ in repairing these DSBs was shown to be
      diminished. Taking advantage of the ability of high linear energy transfer (LET)
      radiation to produce complex DSBs effectively, we investigated how the complexity
      of DSB end structure influences DNA damage responses. An early step in HR is the
      generation of 3'-single strand DNA (SSD) via a process of DNA end resection that
      requires CtIP. To assess this process, we analyzed the level of phosphorylated
      CtIP, as well as RPA phosphorylation and focus formation, which occur on the
      exposed SSD. We show that complex DSBs efficiently activate DNA end resection.
      After heavy ion beam irradiation, resection signals appear both in the vicinity
      of heterochromatic areas, which is also observed after X-irradiation, and
      additionally in euchromatic areas. Consequently, ~85% of complex DSBs are
      subjected to resection in heavy ion particle tracks. Furthermore, around 20-40%
      of G1 cells exhibit resection signals. Taken together, our observations reveal
      that the complexity of DSB ends is a critical factor regulating the choice of DSB
      repair pathway and drastically alters the balance toward resection-mediated
      rejoining. As demonstrated here, studies on DNA damage responses induced by heavy
      ion radiation provide an important tool to shed light on mechanisms regulating
      DNA end resection.

PMID- 24041487
TI  - Genipin ameliorates age-related insulin resistance through inhibiting hepatic
      oxidative stress and mitochondrial dysfunction.
AB  - Insulin resistance (IR) increases with age and plays a key role in the
      pathogenesis of type 2 diabetes mellitus. Oxidative stress and mitochondrial
      dysfunction are supposed to be major factors leading to age-related IR. Genipin,
      an extract from Gardenia jasminoides Ellis fruit, has been reported to stimulate
      insulin secretion in pancreatic islet cells by regulating mitochondrial function.
      In this study, we first investigated the effects of genipin on insulin
      sensitivity and the potential mitochondrial mechanisms in the liver of aging
      rats. The rats were randomly assigned to receive intraperitoneal injections of
      either 25mg/kg genipin or vehicle once daily for 12days. The aging rats showed
      hyperinsulinemia and hyperlipidemia, and insulin resistance as examined by the
      decreased glucose decay constant rate during insulin tolerance test (kITT). The
      hepatic tissues showed steatosis and reduced glycogen content. Hepatic
      malondialdehyde level and mitochondrial reactive oxygen species (ROS) were
      higher, and levels of mitochondrial membrane potential (MMP) and ATP were lower
      as compared with the normal control rats. Administration of genipin ameliorated
      systemic and hepatic insulin resistance, alleviated hyperinsulinemia,
      hyperglyceridemia and hepatic steatosis, relieved hepatic oxidative stress and
      mitochondrial dysfunction in aging rats. Furthermore, genipin not only improved
      insulin sensitivity by promoting insulin-stimulated glucose consumption and
      glycogen synthesis, inhibited cellular ROS overproduction and alleviated the
      reduction of levels of MMP and ATP, but also reversed oxidative stress-associated
      JNK hyperactivation and reduced Akt phosphorylation in palmitate-treated L02
      hepatocytes. In conclusion, genipin ameliorates age-related insulin resistance
      through inhibiting hepatic oxidative stress and mitochondrial dysfunction. 

PMID- 24041489
TI  - Actions of 17beta-estradiol and testosterone in the mitochondria and their
      implications in aging.
AB  - A decline in the mitochondrial functions and aging are two closely related
      processes. The presence of estrogen and androgen receptors and hormone-responsive
      elements in the mitochondria represents the starting point for the investigation
      of the effects of 17beta-estradiol and testosterone on the mitochondrial
      functions and their relationships with aging. Both steroids trigger a complex
      molecular mechanism that involves crosstalk between the mitochondria, nucleus,
      and plasma membrane, and the cytoskeleton plays a key role in these interactions.
      The result of this signaling is mitochondrial protection. Therefore, the
      molecular components of the pathways activated by the sexual steroids could
      represent targets for anti-aging therapies. In this review, we discuss previous
      studies that describe the estrogen- and testosterone-dependent actions on the
      mitochondrial processes implicated in aging.

PMID- 24041490
TI  - Frontal cortical thinning and subcortical volume reductions in early adulthood
      obesity.
AB  - Obesity depends on homeostatic and hedonic food intake behavior, mediated by
      brain plasticity changes in cortical and subcortical structures. The aim of this
      study was to investigate cortical thickness and subcortical volumes of regions
      related to food intake behavior in a healthy young adult sample with obesity.
      Thirty-seven volunteers, 19 with obesity (age=33.7+/-5.7 (20-39) years body-mass
      index (BMI)=36.08+/-5.92 (30.10-49.69)kg/m(2)) and 18 controls (age=32.3+/-5.9
      (21-40) years; BMI=22.54+/-1.94 (19.53-24.97)kg/m(2)) participated in the study.
      Patients with neuropsychiatric or biomedical disorders were excluded. We used
      FreeSurfer software to analyze structural magnetic resonance images (MRI) and
      obtain global brain measures, cortical thickness and subcortical volume
      estimations. Finally, correlation analyses were performed for brain structure
      data and obesity measures. There were no between-group differences in age,
      gender, intelligence or education. Results showed cortical thickness reductions
      in obesity in the left superior frontal and right medial orbitofrontal cortex. In
      addition, the obesity group had lower ventral diencephalon and brainstem volumes
      than controls, while there were no differences in any other subcortical
      structure. There were no statistically significant correlations between brain
      structure and obesity measures. Overall, our work provides evidence of the
      structural brain characteristics associated with metabolically normal obesity. We
      found reductions in cortical thickness, ventral diencephalon and brainstem
      volumes in areas that have been implicated in food intake behavior. 

PMID- 24041491
TI  - Dynamic stability of a human standing on a balance board.
AB  - The neuromuscular system used to stabilize upright posture in humans is a
      nonlinear dynamical system with time delays. The analysis of this system is
      important for improving balance and for early diagnosis of neuromuscular disease.
      In this work, we study the dynamic coupling between the neuromuscular system and
      a balance board-an unstable platform often used to improve balance in young
      athletes, and older or neurologically impaired patients. Using a simple inverted
      pendulum model of human posture on a balance board, we describe a surprisingly
      broad range of divergent and oscillatory CoP/CoM responses associated with
      instabilities of the upright equilibrium. The analysis predicts that a variety of
      sudden changes in the stability of upright postural equilibrium occurs with slow
      continuous deterioration in balance board stiffness, neuromuscular gain, and time
      delay associated with the changes in proprioceptive/vestibular/visual
      neuromuscular feedback. The analysis also provides deeper insight into changes in
      the control of posture that enable stable upright posture on otherwise unstable
      platforms. 

PMID- 24041492
TI  - [Maxillofacial reconstruction with radial forearm osteofasciocutaneous free
      flap].
AB  - INTRODUCTION: Maxillofacial defects often affect various type of tissues and
      require reconstruction using composite flaps. The radial forearm
      osteofasciocutaneous free flap is one of the least used. We present the
      preliminary results of maxillofacial reconstruction using this free flap.
      MATERIALS AND METHODS: We reviewed the records of patients having undergone a
      radial forearm osteofasciocutaneous flap procedure between 2009 and 2011.
      Mandibular defect were staged according to HCL classification. Maxillary defects
      were staged according to Cordeiro and Santamaria's classification. Functional
      results (swallowing and speech) were assessed at the sixth month. RESULTS: The
      mean age of the 10 patients was 60.2 years. The average length of bone defect was
      8 cm. The average cutaneous defect area was 36.8 cm(2). The mandibular defect was
      LCL in six cases, L in one case, and C in one case. The two cases of maxillary
      bone loss were classified IIIa. Six of the 10 microsurgical anastomoses were
      contralateral to the lesion. There was no reconstruction failure. Three patients
      had mild speech disorders, five had moderate speech disorders, and two major
      speech disorders. Four patients had a normal food intake, three patients needed
      mixed food, and three patients liquid food. DISCUSSION: The indications of radial
      forearm osteofasciocutaneous free flap for complex maxillofacial reconstructions
      should be extended. Its vascularization is less compromised by arteritis. Its
      pedicle may be long and adequate for a contralateral anastomosis. It is reliable
      and easy to harvest. But the bone quality is not as good as fibula.

PMID- 24041493
TI  - "Oral amoxicillin as antibiotic prophylaxis before dental surgery - "Faux-pas" or
      "dernier cri"?": T. Schouman response.

PMID- 24041494
TI  - Jugular foramen schwannomas: a single institution patient series.
AB  - Jugular foramen schwannomas are rare. To our knowledge only a small number of
      series including a large number of patients have been reported. We aimed to
      analyse the clinical characteristics, surgical approaches, and outcome of
      patients undergoing treatment for jugular foramen schwannomas via a retrospective
      analysis of departmental records. Data for 28 patients treated for jugular
      foramen schwannomas in the Department of Neurosurgery at our tertiary level
      referral institution between January 2001 and December 2010 were analysed. Most
      patients were in the fourth decade of life, with the duration of symptoms ranging
      from 1 month to 13 years. A skull base approach was used in every surgically
      treated patient. Of the 19 patients for whom radiological follow-up were
      available, complete tumor excision was achieved in 17 patients. Follow-up ranged
      from 3 months to 59 months (mean, 32 months). One patient died and three had
      permanent morbidity in the form of facial nerve palsy. Jugular foramen
      schwannomas are best treated by total surgical resection. Partial resection is
      appropriate for tumors with adhesions to the brainstem and in medically unfit
      patients. Subsequent radiosurgery can be used for small residual tumors.

PMID- 24041496
TI  - Solvent and structural effects on the UV absorption spectra of N-(substituted
      phenyl)-2-cyanoacetamides.
AB  - UV absorption spectra of N-(substituted phenyl)-2-cyanoacetamides have been
      recorded in the range 200-400 nm in the set of selected solvents. The solute
      solvent interactions were analyzed on the basis of linear solvation energy
      relationships (LSER) concept proposed by Kamlet and Taft. The effects of
      substituents on the absorption spectra were interpreted by correlation of
      absorption frequencies with Hammett substituent constant, sigma. It was found
      that substituents significantly change the extent of conjugation. Furthermore,
      the experimental findings were interpreted with the aid of ab initio B3LYP/6
      311G(d,p) method. Electronic energies was calculated by the use of 6
      311++G(3df,3pd) methods with standard polarized continuum model (PCM) for
      inclusion of the solvent effect.

PMID- 24041497
TI  - Ultrasound propagation in trabecular bone: a numerical study of the influence of
      microcracks.
AB  - The accumulation of microdamage in trabecular bone tissue is suspected of being a
      predictive indicator of osteoporosis diagnosis. To quantify this microdamage, the
      Dynamic AcoustoElastic Testing (DAET) method measures the Time Of Flight (TOF)
      and amplitude variations of transmitted ultrasound (US) pulses, while the bone
      sample is submitted to a low frequency sinusoidal hydrostatic pressure
      (opening/closing of microcracks). However, DAET is both sensitive to viscoelastic
      properties changes and microcracks density. To verify the microcracks density
      contribution on DAET results, a numerical approach is proposed. Multliple
      configurations of microdamaged trabecular bone-tissue-like mesh have been
      simulated. A 2D pseudo-spectral time domain numerical model was then developed to
      simulate linear wave propagation in heterogeneous solids. The influence of the
      microcracks number and orientation on the US TOF was particularly investigated.
      Results are discussed and compared with experimental data obtained from DAET
      measurements in trabecular bone samples. 

PMID- 24041495
TI  - Towards the elements of successful insect RNAi.
AB  - RNA interference (RNAi), the sequence-specific suppression of gene expression,
      offers great opportunities for insect science, especially to analyze gene
      function, manage pest populations, and reduce disease pathogens. The accumulating
      body of literature on insect RNAi has revealed that the efficiency of RNAi varies
      between different species, the mode of RNAi delivery, and the genes being
      targeted. There is also variation in the duration of transcript suppression. At
      present, we have a limited capacity to predict the ideal experimental strategy
      for RNAi of a particular gene/insect because of our incomplete understanding of
      whether and how the RNAi signal is amplified and spread among insect cells.
      Consequently, development of the optimal RNAi protocols is a highly empirical
      process. This limitation can be relieved by systematic analysis of the molecular
      physiological basis of RNAi mechanisms in insects. An enhanced conceptual
      understanding of RNAi function in insects will facilitate the application of RNAi
      for dissection of gene function, and to fast-track the application of RNAi to
      both control pests and develop effective methods to protect beneficial insects
      and non-insect arthropods, particularly the honey bee (Apis mellifera) and
      cultured Pacific white shrimp (Litopenaeus vannamei) from viral and parasitic
      diseases. 

PMID- 24041498
TI  - Microfabrication of stacks of acoustic matching layers for 15 MHz ultrasonic
      transducers.
AB  - This paper presents a novel method used to manufacture stacks of multiple
      matching layers for 15 MHz piezoelectric ultrasonic transducers, using
      fabrication technology derived from the MEMS industry. The acoustic matching
      layers were made on a silicon wafer substrate using micromachining techniques,
      i.e., lithography and etch, to design silicon and polymer layers with the desired
      acoustic properties. Two matching layer configurations were tested: a double
      layer structure consisting of a silicon-polymer composite and polymer and a
      triple layer structure consisting of silicon, composite, and polymer. The
      composite is a biphase material of silicon and polymer in 2-2 connectivity. The
      matching layers were manufactured by anisotropic wet etch of a (110)-oriented
      Silicon-on-Insulator wafer. The wafer was etched by KOH 40 wt%, to form 83 MUm
      deep and 4.5mm long trenches that were subsequently filled with Spurr's epoxy,
      which has acoustic impedance 2.4 MRayl. This resulted in a stack of three layers:
      The silicon substrate, a silicon-polymer composite intermediate layer, and a
      polymer layer on the top. The stacks were bonded to PZT disks to form acoustic
      transducers and the acoustic performance of the fabricated transducers was tested
      in a pulse-echo setup, where center frequency, -6 dB relative bandwidth and
      insertion loss were measured. The transducer with two matching layers was
      measured to have a relative bandwidth of 70%, two-way insertion loss 18.4 dB and
      pulse length 196 ns. The transducers with three matching layers had fractional
      bandwidths from 90% to 93%, two-way insertion loss ranging from 18.3 to 25.4 dB,
      and pulse lengths 326 and 446 ns. The long pulse lengths of the transducers with
      three matching layers were attributed to ripple in the passband.

PMID- 24041499
TI  - The standard concentric needle cannula cannot replace the Macro EMG electrode.
AB  - OBJECTIVE: To establish the usefulness of the single use and affordable standard
      concentric EMG electrode as a substitute for the expensive standard macro
      electrode. METHODS: Macro EMG performed with macro electrode is compared with
      recordings from the uninsulated cannula of a standard EMG electrode at two
      different recording depths in the tibialis anterior muscle. This was performed
      both in muscles with signs of collateral reinnervation and without. RESULTS: The
      amplitude of the motor units recorded with the uninsulated concentric needle
      cannula were lower for the deeply recorded motor units compared to motor unit
      potential (MUP) amplitudes recorded with the standard macro electrode. The deeply
      recorded concentric needle (CN) cannula recorded MUPs amplitudes were also lower
      than superficially recorded CN cannula MUPs. The standard Macro EMG signals show
      no difference between deeply and superficially recorded motor units. CONCLUSION:
      The uninsulated cannula of the concentric needle electrode cannot replace the
      standard Macro EMG electrode due to technical reasons, probably from different
      effects of shunting of the bare cannula in deep vs. superficially recorded motor
      units. SIGNIFICANCE: The standard CN electrode could not be used as substitute
      for the standard Macro EMG needle.

PMID- 24041500
TI  - Expression and purification of bioactive hemagglutinin protein of highly
      pathogenic avian influenza A (H5N1) in silkworm larvae.
AB  - The hemagglutinin (HA) of avian influenza viruses plays a very important role in
      the infection of host cells. In this study, the HA gene of the highly pathogenic
      avian influenza H5N1 virus was cloned and expressed in silkworm larvae. The
      expressed recombinant HA (rHA) was purified using fetuin-agarose chromatography
      and Superdex 200 10/300 GL gel filtration chromatography, and the identity of
      purified rHA was confirmed by SDS-PAGE and Western blot. Approximately 500 MUg of
      purified rHA was obtained from a total of 30 silkworm larvae, suggesting the high
      efficiency of the silkworm expression system. The purified rHA bound to a rabbit
      polyclonal antibody against influenza A virus H5N1 (avian flu) HA, suggesting its
      antigenicity and potential application in vaccine development. Gel filtration
      chromatography showed that purified HA was present in the void volume fractions,
      indicating that rHA may form an oligomer. The rHA bound to
      poly{Neu5Acalpha2,3LacNAcbeta-O[(CH2)5NHCO]2(CH2)5NH-/gamma-PGA}, which mimics an
      avian type receptor, but did not bind to gamma-polyglutamic acid or human type
      receptor mimic, poly{Neu5Acalpha2,6LacNAcbeta-O[(CH2)5NHCO]2(CH2)5NH-/gamma-PGA},
      suggesting that it could be utilized as a blocking agent against infection by
      highly pathogenic influenza viruses.

PMID- 24041501
TI  - Acceleration of the depolymerization of amyloid beta fibrils by ultrasonication.
AB  - Amyloid fibrils, rigid and filamentous aggregates associated with various
      diseases, are often difficult to depolymerize into monomers. Ultrasonication is a
      strong agitation that accelerates nucleation above the critical concentration of
      amyloid fibrillation. We examined the effects of ultrasonication on the fibrils
      of amyloid beta(1-40) as well as on monomers. Ultrasonic pulses accelerated
      spontaneous fibrillation when the peptide concentration was above 1MUM. On the
      other hand, ultrasonic pulses accelerated the depolymerization of fibrils into
      monomers at 1MUM. These results indicate that, although amyloid fibrillation is a
      reversible process determined by thermodynamic stability, kinetically trapped
      supersaturation and physical difficulty of dissolving rigid fibrils prevent the
      smooth phase transitions. We propose that, in addition to accelerating the
      nucleation of fibrillation and fragmentation of fibrils above the critical
      concentration, ultrasonication is useful for dissolving fibrils below the
      critical concentration. 

PMID- 24041502
TI  - Cooperative dynamics of a DNA polymerase replicating complex.
AB  - Engineered DNA polymerases continue to be the workhorses of many applications in
      biotechnology, medicine and nanotechnology. However, the dynamic interplay
      between the enzyme and the DNA remains unclear. In this study, we performed an
      extensive replica exchange with flexible tempering (REFT) molecular dynamics
      simulation of the ternary replicating complex of the archaeal family B DNA
      polymerase from the thermophile Thermococcus gorgonarius, right before the
      chemical step. The convoluted dynamics of the enzyme are reducible to rigid-body
      motions of six subdomains. Upon binding to the enzyme, the DNA double helix
      conformation changes from a twisted state to a partially untwisted state. The
      twisted state displays strong bending motion, whereby the DNA oscillates between
      a straight and a bent conformation. The dynamics of double-stranded DNA are
      strongly correlated with rotations of the thumb toward the palm, which suggests
      an assisting role of the enzyme during DNA translocation. In the complex, the
      primer-template duplex displays increased preference for the B-DNA conformation
      at the n-2 and n-3 dinucleotide steps. Interactions at the primer 3' end indicate
      that Thr541 and Asp540 are the acceptors of the first proton transfer in the
      chemical step, whereas in the translocation step both residues hold the primer 3'
      terminus in the vicinity of the priming site, which is crucial for high
      processivity. 

PMID- 24041503
TI  - Late adolescent expression of GluN2B transmission in the prefrontal cortex is
      input-specific and requires postsynaptic protein kinase A and D1 dopamine
      receptor signaling.
AB  - BACKGROUND: Refinement of mature cognitive functions, such as working memory and
      decision making, typically takes place during adolescence. The acquisition of
      these functions is linked to the protracted development of the prefrontal cortex
      (PFC) and dopamine facilitation of glutamatergic transmission. However, the
      mechanisms that support these changes during adolescence remain elusive. METHODS:
      Electrophysiological recordings (in vitro and in vivo) combined with
      pharmacologic manipulations were employed to determine how N-methyl-D-aspartate
      transmission in the medial PFC changes during the adolescent transition to
      adulthood. The relative contribution of GluN2B transmission and its modulation by
      postsynaptic protein kinase A and D1 receptor signaling were determined in two
      distinct age groups of rats: postnatal day (P)25 to P40 and P50 to P80. RESULTS:
      We found that only N-methyl-D-aspartate receptor transmission onto the apical
      dendrite of layer V pyramidal neurons undergoes late adolescent remodeling due to
      a functional emergence of GluN2B function after P40. Both protein kinase A and
      dopamine D1 receptor signaling are required for the functional expression of
      GluN2B transmission and to sustain PFC plasticity in response to ventral
      hippocampal, but not basolateral amygdala, inputs. CONCLUSIONS: Thus, the late
      adolescent acquisition of GluN2B function provides a mechanism for dopamine D1
      mediated regulation of PFC responses in an input-specific manner.

PMID- 24041506
TI  - Novel tools, classic techniques: evolutionary studies using primate pluripotent
      stem cells.
AB  - Recent applications of genomic tools on the analysis of alterations unique to our
      species coupled with a growing number of neuroanatomical studies across primates
      provide an unprecedented opportunity to compile different levels of human brain
      evolution into a complex whole. Applications of induced pluripotent stem cell
      (iPSC) technology, capable of reprogramming somatic tissue of different species
      and generating species-specific neuronal phenotypes, for the first time offer an
      opportunity to test specific evolutionary hypotheses in a field of inquiry that
      has been long plagued by the limited availability of research specimens. In this
      review, we will focus specifically on the experimental role of iPSC technology as
      applied to the analysis of neocortical pyramidal neurons. Pyramidal neurons
      emerge as particularly suitable for testing evolutionary scenarios, since they
      form the most common morphological class of neurons in the cortex, display
      morphological variations across different cortical areas and cortical layers that
      appear species-specific, and express unique molecular signatures. Human and
      nonhuman primate iPSC-derived neurons may represent a unique biological resource
      to elucidate the phenotypic differences between humans and other hominids. As the
      typical morphology of pyramidal neurons tends to be compromised in neurological
      disorders, application of iPSC technology to the analysis of pyramidal neurons
      could not only bring new insights into human adaptation but also offer
      opportunities to link biomedical research with studies of the origins of the
      human species. 

PMID- 24041507
TI  - Analysis of anabolic steroids in urine by gas chromatography-microchip
      atmospheric pressure photoionization-mass spectrometry with chlorobenzene as
      dopant.
AB  - A gas chromatography-microchip atmospheric pressure photoionization-tandem mass
      spectrometry (GC-MUAPPI-MS/MS) method was developed for the analysis of anabolic
      androgenic steroids in urine as their trimethylsilyl derivatives. The method
      utilizes a heated nebulizer microchip in atmospheric pressure photoionization
      mode (MUAPPI) with chlorobenzene as dopant, which provides high ionization
      efficiency by producing abundant radical cations with minimal fragmentation. The
      performance of GC-MUAPPI-MS/MS was evaluated with respect to repeatability,
      linearity, linear range, and limit of detection (LOD). The results confirmed the
      potential of the method for doping control analysis of anabolic steroids.
      Repeatability (RSD<10%), linearity (R(2)>=0.996) and sensitivity (LODs 0.05
      0.1ng/mL) were acceptable. Quantitative performance of the method was tested and
      compared with that of conventional GC-electron ionization-MS, and the results
      were in good agreement. 

PMID- 24041504
TI  - Remember the future II: meta-analyses and functional overlap of working memory
      and delay discounting.
AB  - Previously we showed that working memory training decreased the discounting of
      future rewards in stimulant addicts without affecting a go/no-go task. While a
      relationship between delay discounting and working memory is consistent with
      other studies, the unique brain regions of plausible causality between these two
      abilities have yet to be determined. Activation likelihood estimation meta
      analyses were performed on foci from studies of delay discounting (DD = 449),
      working memory (WM = 452), finger tapping (finger tapping = 450), and response
      inhibition (RI = 450). Activity maps from relatively less (finger tapping) and
      more (RI) demanding executive tasks were contrasted with maps of DD and WM.
      Overlap analysis identified unique functional coincidence between DD and WM. The
      anterior cingulate cortex was engaged by all tasks. Finger tapping largely
      engaged motor-related brain areas. In addition to motor-related areas, RI engaged
      frontal brain regions. The right lateral prefrontal cortex was engaged by RI, DD,
      and WM and was contrasted out of overlap maps. A functional cluster in the
      posterior portion of the left lateral prefrontal cortex emerged as the largest
      location of unique overlap between DD and WM. A portion of the left lateral
      prefrontal cortex is a unique location where delay discounting and working memory
      processes overlap in the brain. This area, therefore, represents a therapeutic
      target for improving behaviors that rely on the integration of the recent past
      with the foreseeable future. 

PMID- 24041505
TI  - Glycogen synthase kinase-3 inhibitors reverse deficits in long-term potentiation
      and cognition in fragile X mice.
AB  - BACKGROUND: Identifying feasible therapeutic interventions is crucial for
      ameliorating the intellectual disability and other afflictions of fragile X
      syndrome (FXS), the most common inherited cause of intellectual disability and
      autism. Hippocampal glycogen synthase kinase-3 (GSK3) is hyperactive in the mouse
      model of FXS (FX mice), and hyperactive GSK3 promotes locomotor hyperactivity and
      audiogenic seizure susceptibility in FX mice, raising the possibility that
      specific GSK3 inhibitors may improve cognitive processes. METHODS: We tested if
      specific GSK3 inhibitors improve deficits in N-methyl-D-aspartate receptor
      dependent long-term potentiation at medial perforant path synapses onto dentate
      granule cells and dentate gyrus-dependent cognitive behavioral tasks. RESULTS:
      GSK3 inhibitors completely rescued deficits in long-term potentiation at medial
      perforant path-dentate granule cells synapses in FX mice. Furthermore,
      synaptosomes from the dentate gyrus of FX mice displayed decreased inhibitory
      serine-phosphorylation of GSK3beta compared with wild-type littermates. The
      potential therapeutic utility of GSK3 inhibitors was further tested on dentate
      gyrus-dependent cognitive behaviors. In vivo administration of GSK3 inhibitors
      completely reversed impairments in several cognitive tasks in FX mice, including
      novel object detection, coordinate and categorical spatial processing, and
      temporal ordering for visual objects. CONCLUSIONS: These findings establish that
      synaptic plasticity and cognitive deficits in FX mice can be improved by
      intervention with inhibitors of GSK3, which may prove therapeutically beneficial
      in FXS.

PMID- 24041508
TI  - Analytical silica monoliths with submicron macropores: current limitations to a
      direct morphology-column efficiency scaling.
AB  - Shrinking the structural elements of a particulate bed or monolith (i.e., the
      particle or domain size) yields more efficient columns only when the homogeneity
      of the bed can be conserved in that process. We investigate this complex issue
      for a set of 2nd generation analytical silica monoliths with macropores reaching
      submicron dimensions using chromatographic methods, mercury intrusion
      porosimetry, scanning electron microscopy, and confocal laser scanning microscopy
      (CLSM), and present eddy dispersion simulations and a chord length distribution
      analysis for the CLSM-based physical reconstructions at macropore resolution. The
      combined results allow us to identify relevant morphological advances made from
      1st to 2nd generation monoliths and additionally highlight the current
      limitations to a direct morphology-efficiency scaling with respect to the
      performance that can be accomplished in HPLC practice with these columns. Whereas
      the improvement in radial homogeneity from 1st to 2nd generation silica monoliths
      is represented by a dramatic increase in column efficiency, the further reduction
      of macropore size in the 2nd generation monoliths does not lead to the expected
      improvement of plate height data, although these monoliths realize submicron
      macropores at a simultaneously conserved bulk macropore space homogeneity and
      negligible radial heterogeneity. Our study implies that limitations to further
      improved column efficiency arise from the intrinsic border effects of the used
      4.6mm i.d. analytical columns. This includes the sample distribution onto the
      monoliths and asynchronous sample collection through the endfittings at the
      column inlet and outlet, respectively. Only when these effects are reduced will
      additionally improved 2nd generation monoliths live up to column efficiencies,
      which are envisioned for them based on their morphological properties. 

PMID- 24041509
TI  - Profiling of soil fatty acids using comprehensive two-dimensional gas
      chromatography with mass spectrometry detection.
AB  - Profiling of phospholipid fatty acids (PLFA) represents a challenging goal for
      distinguishing the diversity of microbial communities and biomass in the complex
      and heterogeneous soil ecosystem. Comprehensive two-dimensional gas
      chromatography (GC*GC) coupled with simultaneous flame ionisation and mass
      spectrometry detection was applied as a culture-independent method for PLFA
      profiling of microbial classification in forest soil. A number of column sets
      were evaluated for the GC*GC separation of fatty acid methyl esters (FAME). Due
      to better isomeric separation and compound patterns on the 2D contour plot, an
      apolar-polar column combination was selected for soil microbial PLFA
      characterisation. A comprehensive view of PLFA composition with carbon chain
      length varying from 12 to 20 was observed in forest soil samples, with the
      commonly reported bacterial FAME of iso-/anteiso-, methyl-branched-, cyclopropyl
      , and hydroxyl-substituted FA identified by their mass spectral and retention
      time according to authentic standards. Notably, some uncommon oxygenated FAME
      were found in high abundance and were further characterised by GC*GC coupled with
      high resolution mass spectrometry. This tentatively revealed geometric pairs of
      methyl 9,10-epoxyoctadecanoate isomers. 

PMID- 24041510
TI  - Determination of adsorption isotherms in supercritical fluid chromatography.
AB  - In this study we will demonstrate the potential of modern integrated commercial
      analytical SFC-systems for rapid and reliable acquisition of thermodynamic data.
      This will be done by transferring the following adsorption isotherm determination
      methods from liquid chromatography (LC) to supercritical fluid chromatography
      (SFC): Elution by Characteristic Points (ECP), the Retention Time Method (RTM),
      the Inverse Method (IM) and the Perturbation Peak (PP) method. In order to
      transfer these methods to SFC in a reliable, reproducible way we will demonstrate
      that careful system verification using external sensors of mass flow, temperature
      and pressure are needed first. The adsorption isotherm data generated by the
      different methods were analyzed and compared and the adsorption isotherms ability
      to predict new experimental elution profiles was verified by comparing
      experiments with simulations. It was found that adsorption isotherm data
      determined based on elution profiles, i.e., ECP, IM and RTM, were able to
      accurately predict overloaded experimental elution profiles while the more
      tedious and time-consuming PP method, based on small injections on concentration
      plateaus, failed in doing so. 

PMID- 24041511
TI  - Theoretical evaluation of the advantages and limitations of constant pressure
      versus constant flow rate gradient elution separation in supercritical fluid
      chromatography.
AB  - This study reports on the possible advantages of switching from constant flow
      (cF) based gradient elution separations to constant pressure (cP) based ones in
      Supercritical fluid chromatography (SFC) by means of mathematical models. All the
      important parameters (e.g. viscosity) were fitted as a function of pressure and
      mol% methanol in CO2. It is shown that when switching towards a cP approach in
      SFC, a time gain of 34% at the end of a 0 to 50% methanol in CO2 gradient is
      expected. Actual analysis time gains depend on the point at which it is evaluated
      (e.g. up to 41% after the equilibration step). Due to the dependence of retention
      on density, cF- and cP-mode do not yield the same selectivity even if the same
      volumetric-based gradient program is used. Because the components experience a
      higher average pressure in the cP-mode, the apparent retention factor is slightly
      lower. 

PMID- 24041512
TI  - Isocratic and gradient impedance plot analysis and comparison of some recently
      introduced large size core-shell and fully porous particles.
AB  - The intrinsic kinetic performance of three recently commercialized large size
      (>=4MUm) core-shell particles packed in columns with different lengths has been
      measured and compared with that of standard fully porous particles of similar and
      smaller size (5 and 3.5MUm, respectively). The kinetic performance is compared in
      both absolute (plot of t0 versus the plate count N or the peak capacity np for
      isocratic and gradient elution, respectively) and dimensionless units. The latter
      is realized by switching to so-called impedance plots, a format which has been
      previously introduced (as a plot of t0/N(2) or E0 versus Nopt/N) and has in the
      present study been extended from isocratic to gradient elution (where the
      impedance plot corresponds to a plot of t0/np(4) versus np,opt(2)/np(2)). Both
      the isocratic and gradient impedance plot yielded a very similar picture: the
      clustered impedance plot curves divide into two distinct groups, one for the core
      shell particles (lowest values, i.e. best performance) and one for the fully
      porous particles (highest values), confirming the clear intrinsic kinetic
      advantage of core-shell particles. If used around their optimal flow rate, the
      core-shell particles displayed a minimal separation impedance that is about 40%
      lower than the fully porous particles. Even larger gains in separation speed can
      be achieved in the C-term regime. 

PMID- 24041513
TI  - Response to: cause of death and correlation with autopsy findings in burns
      patient.

PMID- 24041514
TI  - Percutaneous dilational and surgical tracheostomy in burn patients: incidence of
      complications and dysphagia.
AB  - The aim of this study is to evaluate the incidence of complications and dysphagia
      in relation to the timing of tracheostomy and tracheostomy technique in 49
      consecutive adult burn patients. We analysed prospectively collected data.
      Bronchoscopy was used to diagnose tracheal stenosis and a modified Evans blue dye
      test was used to diagnose dysphagia. Eighteen patients received a percutaneous
      dilatational tracheostomy (PDT) and thirty-one patients received an open surgical
      tracheostomy (OST). Eight patients developed significant complications (16%)
      following tracheostomy, there is no difference in the incidence of complications;
      post op infection, stoma infection or tracheal stenosis between PDT and OST
      groups. Patients with full thickness neck burn who developed complications had a
      tracheostomy significantly earlier following autografting (p=0.05). Failed
      extubation is associated with dysphagia (p=0.02) whereas prolonged intubation and
      ventilation prior to tracheostomy independently predicts dysphagia (p=0.03). We
      conclude that there is no difference in the complication rates for PDT and OST in
      our burn patients. We recommend early closure of neck burns and tracheostomy
      through fully adherent autograft or at least 10 days after grafting to reduce
      stomal infections. For patients with no neck burn, we support early tracheostomy
      to reduce the likelihood of dysphagia. 

PMID- 24041515
TI  - Intermediate-level disinfection with accelerated hydrogen peroxide prevents
      accumulation of bacteria in VersajetTM tubing during repeated daily debridement
      using simulated-use testing with an inoculated pork hock.
AB  - OBJECTIVE: This study assesses the feasibility of using the VersajetTM system
      (VJS) on an inoculated pork hock (PH) skin surface sequentially for 8 days with
      daily cleaning and intermediate-level disinfection (ILD). METHODS: Daily, PHs
      were inoculated with bacteria suspended in artificial test soil (ATS). An ILD
      protocol with accelerated hydrogen peroxide (AHP, OxivirTB((r))) was employed to
      clean and disinfect the VJS between debridements. RESULTS: PH skin contains 6.1
      6.8*10(6)cfu/cm(2) bacteria. Bacterial counts in the handpiece and discharge
      hoses immediately after debridement of the PHs, and before cleaning, increased
      throughout the study period (5.19-6.43log10cfu/mL). Cleaning with the ILD
      protocol was reduced bacterial counts on the VJS by 6-log. Protein, a surrogate
      marker of organic contamination, was also reduced post-cleaning and ILD. Compared
      to a maximum post-debridement level of protein (57.9 MUg/mL) obtained before ILD,
      VJS protein levels dropped to 9.8 (handpiece) and 13.8 MUg/mL (discharge hose).
      CONCLUSIONS: Disinfection of the handpiece and discharge hose after debridement
      with AHP resulted in a 6-log reduction in bacterial count and 4.2 fold reduction
      in protein. An ILD protocol with an AHP may be a feasible method for serial skin
      surface debridements with the VJS for up to eight days.

PMID- 24041516
TI  - Paediatric burns: from the voice of the child.
AB  - INTRODUCTION: Despite burns being common in children, research into the
      psychological experience and trauma remains limited. Improvements in the
      professional understanding of children's experiences will assist in improving
      holistic care. PURPOSE: This study uses phenomenology, a qualitative methodology
      to explore the psychological experiences following a burn injury in children.
      METHODS: In-depth interviews were conducted six months after burn with 12 (six
      girls and six boys) children who underwent surgery for a burn. The children were
      aged eight to 15 years. The interview examined the overall experience of children
      and included probing questions exploring participants' perceptions, thoughts and
      feelings. Transcripts were analysed according to the seven-step Coliazzi method.
      Relationships between themes were explored to identify core concepts. RESULTS:
      The findings demonstrated that trauma was central to the burn experience and
      comprised two phases: the burn trauma and the recovery trauma. Six themes emerged
      as a result of this experience: ongoing recurrent trauma; returning to normal
      activities; behavioural changes; scarring-the permanent reminder; family and
      adaptation. CONCLUSION: This research has clinical implications as its findings
      can be used to inform clinical care at all stages of the burn journey. These
      research conclusions could be used to develop comprehensive information and
      support management plans for children. This would complement and support the
      surgical and medical treatment plan, providing direction for comprehensive
      service delivery and improved psychosocial outcomes in children.

PMID- 24041517
TI  - Integrating social epidemiological methods into self-immolation studies.

PMID- 24041518
TI  - A new method of microskin autografting with a Vaseline-based moisture dressing on
      granulation tissue.
AB  - In the conventional method of microskin autografting, aggressive early excision
      is adopted, followed by coverage with a microskin-allograft complex to close
      extensive burn wounds. However, early excision is always associated with a defect
      of viable tissue, resulting in massive blood loss and causing high risk to aged
      patients or those with other systemic diseases. We developed a new method in
      which an eschar thinning operation was first adopted, followed by raising
      granulation tissue and microskin autografting, which was covered by a Vaseline
      based moisture dressing. A total of 52 patients were included in this study and
      randomly assigned to the control group (n=26) and the experimental group (n=26)
      for the conventional method and the new method, respectively. The re
      epithelisation rate on the 21st day after autografting indicated that there was
      no significant difference between both groups. There was also no significant
      difference between the two groups when the re-epithelialisation rate was compared
      with the type of organisms cultured. However, the Vancouver Burn Skin Score
      (VBSS) results demonstrated a significant improvement of cosmetic appearance in
      the experimental group (score=2.1) as compared to the control group (score=3.9).
      The new method also showed other advantages, including less blood loss, shorter
      surgical duration and lower cost of surgery. From this prospective study, it can
      be concluded that the new method can be an alternative to the conventional
      microskin autografting procedure. 

PMID- 24041519
TI  - Inhalation injury or mechanical ventilation: which is the true killer in burn
      patients?

PMID- 24041520
TI  - Cervical metastases from maxillary squamous cell carcinoma: retrospective
      analysis and review of the literature.
AB  - The purpose of this study was to define the incidence of cervical metastasis in
      squamous cell carcinoma (SCC) of the maxillary alveolus, hard palate and gingiva;
      to identify patterns of locoregional failure and to assess survival outcomes. We
      retrospectively analysed 30 patients treated for SCC of the maxillary alveolus
      and hard palate between 2000 and 2010. Parameters assessed included the incidence
      of cervical metastasis at presentation and recurrence, paying particular
      attention to tumour staging and survival outcomes. Of our 30 patients, 25 were
      confirmed to have T4 SCC of the maxillary alveolus and hard palate with bone
      invasion. Cervical metastases had been noted in 7 (23%) patients at initial
      presentation. A total of 9 (36%) patients developed regional failure in the pT4
      SCC group shortly after primary resection. Patients with advanced primary SCC of
      the hard palate and maxillary alveolus (particularly when there was bone
      invasion) showed high rates of regional failure, and in most cases successful
      salvage was not achieved. Based on our findings and a review of the existing
      literature we strongly recommend elective neck dissection for patients with pT4
      SCC of the maxillary alveolus and hard palate. 

PMID- 24041521
TI  - Opening wedge distal femoral varus osteotomy for lateral compartment
      osteoarthritis in the valgus knee.
AB  - INTRODUCTION: Osteotomy aims to reduce pain and the rate of progression of
      arthritis by correcting deformity and offloading the affected compartment. This
      study reports the results of a case series of opening wedge distal femoral varus
      osteotomies for valgus lateral osteoarthritis of the knee. PATIENTS AND METHODS:
      Eighteen patients underwent osteotomy surgery (21 knees) with the aim of
      correcting the mechanical axis to 48-50% from medial to lateral. RESULTS: The
      mean follow-up for the study population was 4.5 years (range 1.6 to 9.2 years).
      Four patients underwent conversion to arthroplasty at a mean time of 3.3 years
      postosteotomy. Kaplan-Meier analysis demonstrates a cumulative survival of 79% at
      5 years. In the remaining 17 osteotomies, all patients reported that outcome
      measures improved from baseline. However, only the IKDC and pain subdomain of
      KOOS showed a statistically significant and clinically relevant difference. Re
      operation for non-arthroplasty related surgery was common. In part this was due
      to symptoms related to prominence of metalwork (10). Other reasons included non
      union (1), loss of correction (2), infection (1), and persistent symptoms (2).
      CONCLUSION: Cumulative survival of opening wedge DFVO is comparable with that
      reported in closing wedge series. Clinically relevant differences in the IKDC and
      KOOS pain scores suggest that opening wedge DFVO is a useful option in the
      management of valgus gonarthrosis. However, DFVO is a technically demanding
      procedure and re-operation, particularly for removal of metalwork, is common.

PMID- 24041522
TI  - 1H nuclear magnetic resonance based-metabolomic characterization of Peucedani
      Radix and simultaneous determination of praeruptorin A and praeruptorin B.
AB  - As a widely used traditional herbal medicine, it is crucial to characterize the
      holistic metabolic profile of Peucedani Radix (Chinese name: Qian-hu). However,
      it is quite arduous to obtain the whole picture of chemical constituents
      appropriately with the existing analytical techniques that were based on HPLC-UV
      or LC-MS/MS system. In present investigation, nuclear magnetic resonance (NMR)
      spectroscopy coupled with principal components analysis (PCA) was introduced to
      metabolomic characterization of Qian-hu crude extracts without any
      chromatographic separation. In addition, the contents of praeruptorin A (PA) and
      proaeruptorin B (PB) in Qian-hu were simultaneously determined using quantitative
      (1)H NMR (q(1)H NMR) spectroscopy. Eighteen reference compounds (1-18), which
      were purified from this herbal drug extract previously, were recruited for the
      assignment of the protonic signals in the (1)H NMR spectra. Following PCA, 15
      batches of Peucedani Radix were divided into two groups (I and II), and angular
      type pyranocoumarins, in particular PA and PB, as well as 5-methoxycoumarin were
      demonstrated as the predominant markers being responsible for the distinguishment
      of Qian-hu from different districts. The contents of the two analytes (PA & PB)
      were calculated by the relative ratio of the integral values of the target peak
      for each compound to the known amount of the internal standard, formononetin
      (IS). The lower limits of quantitation were determined as 19.5MUg/mL for both PA
      and PB. The quantitative results indicated that the contents of PA and PB showed
      quite variable qualities among different extract samples. Above all, (1)H NMR
      spectroscopy, that could not only provide comprehensive profiles of the
      metabolites but also achieve convenient determination of praeruptorin A and
      praeruptorin B, is a promising means for evaluating the medicinal samples of
      Peucedani Radix.

PMID- 24041523
TI  - Clinical significance of white matter changes.
AB  - Although their clinical significance has long been debated, it has now been well
      established, both from cross-sectional and longitudinal studies, that white
      matter lesions on magnetic resonance imaging are associated with a number of
      adverse outcomes, including cognitive impairment, functional disability, death,
      neurologic problems, and depression. Novel imaging methods now allow testing of
      models of the pathogenesis of such lesions, which will open new avenues for
      therapeutic intervention to try to prevent or delay the developments of such
      changes. 

PMID- 24041524
TI  - PTSD checklist scoring rules for elderly Veterans Affairs outpatients.
AB  - OBJECTIVE: To assess the diagnostic performance of the PTSD Checklist (PCL) for
      three age groups (<50, 50-64, and >=65 years). METHODS: The PCL was compared with
      the Clinician Administered PTSD Scale, a gold standard for the diagnosis of post
      traumatic stress disorder. Receiver operating characteristic curves and the
      corresponding area under the receiver operating characteristic curve (AUC) and
      measures of sensitivity and specificity were used to assess the performance of
      and to determine optimal cutscores for the PCL across the three groups. Analyses
      were based on 858 randomly selected primary care patients who participated in a
      study conducted at four Veterans Administration medical centers. RESULTS: AUCs
      were high for all three age groups (87.55%-88.26%), and there were no significant
      differences in AUCs across age groups chi(2). Optimal cutscores, however, varied
      considerably: 24 for the oldest group, 34 for the middle group, and 43 for the
      youngest group. CONCLUSION: Recommend use of lower PCL cutscore for older
      Veterans Administration primary care patients.

PMID- 24041525
TI  - Controlling eutrophication by combined bloom precipitation and sediment
      phosphorus inactivation.
AB  - The hypothesis that the combination of the flocculent polyaluminium chloride
      (PAC) with the lanthanum-modified bentonite Phoslock((r)) (Flock & Lock) could
      sink effectively a water bloom of cyanobacteria and could shift a turbid,
      cyanobacteria infested lake to a clear water lake was tested in a controlled
      laboratory experiment and a whole lake experiment. In the laboratory, a
      relatively low dose of the flocculent PAC (2.2 and 4.4 mg Al l(-1)) was
      insufficient to sediment positively buoyant cyanobacteria (Microcystis
      aeruginosa). Similarly, the lanthanum modified clay (dosed at 390 mg l(-1)) was
      insufficient to sediment the positively buoyant cyanobacteria. However, the
      combination of PAC and Phoslock((r)) effectively sedimented cyanobacteria flocks.
      Likewise, a combined treatment of 2 tons PAC and 18 tons Phoslock((r)) in Lake
      Rauwbraken in April 2008 effectively sedimented a developing cyanobacteria bloom
      of Aphanizomenon flos-aquae. The average chlorophyll-a concentration in the two
      years prior to this Flock & Lock treatment was 19.5 (+/-36.5) MUg l(-1), while it
      was as low as 3.7 (+/-4.5) MUg l(-1) in the years following the treatment. The
      combined treatment effectively reduced the amount of total phosphorus (TP) in the
      water column from on average 169 (+/-126) MUg P l(-1) before the application to
      14 (+/-15) MUg P l(-1) after the treatment. Based on mean summer chlorophyll-a
      and TP concentrations, the lake was shifted from a eutrophic/hypertrophic state
      to an oligo/mesotrophic state. From directly after treatment in April 2008 until
      and including 2013, Lake Rauwbraken remained in an oligo-mesotrophic clear water
      state with TP reduced to less than 10% of the pre-treatment. This result shows
      that eutrophication in relatively small, isolated, stratifying lakes can be
      restored by targeting both water column and sediment P using a combination of
      flocculent and solid phase P-sorbent.

PMID- 24041526
TI  - UV-induced photochemical heterogeneity of dissolved and attached organic matter
      associated with cyanobacterial blooms in a eutrophic freshwater lake.
AB  - Cyanobacterial blooms represent a significant ecological and human health problem
      worldwide. In aquatic environments, cyanobacterial blooms are actually surrounded
      by dissolved organic matter (DOM) and attached organic matter (AOM) that bind
      with algal cells. In this study, DOM and AOM fractionated from blooming
      cyanobacteria in a eutrophic freshwater lake (Lake Taihu, China) were irradiated
      with a polychromatic UV lamp, and the photochemical heterogeneity was
      investigated using fluorescence excitation-emission matrix (EEM)-parallel factor
      (PARAFAC) analysis and synchronous fluorescence (SF)-two dimensional correlation
      spectroscopy (2DCOS). It was shown that a 6-day UV irradiation caused more
      pronounced mineralization for DOM than AOM (59.7% vs. 41.9%). The EEM-PARAFAC
      analysis identified one tyrosine-, one humic-, and two tryptophan-like components
      in both DOM and AOM, and high component photodegradation rates were observed for
      DOM versus AOM (k > 0.554 vs. <0.519). Moreover, SF-2DCOS found that the
      photodegradation of organic matters followed the sequence of tyrosine-like >
      humic-like > tryptophan-like substances. Humic-like substances promoted the
      indirect photochemical reactions, and were responsible for the higher
      photochemical rate for DOM. The lower photodegradation of AOM benefited the
      integrality of cells in cyanobacterial blooms against the negative impact of UV
      irradiation. Therefore, the photochemical behavior of organic matter was related
      to the adaptation of enhanced-duration cyanobacterial blooms in aquatic
      environments.

PMID- 24041527
TI  - A novel post denitrification configuration for phosphorus recovery using
      polyphosphate accumulating organisms.
AB  - Enhanced biological phosphorus removal (EBPR) has been widely used to remove
      phosphorus (P) from wastewater. In this study we report a novel modification to
      the EBPR approach, namely enhanced biological phosphorus removal and recovery
      (EBPR-r) that facilitates biological recovery of P from wastewater using a post
      denitrification configuration. The novel approach consists of two major steps. In
      the first step, a biofilm of phosphorus accumulating organisms (PAOs) is exposed
      to a wastewater stream in the absence of active aeration, during which P is taken
      up by the biofilm using nitrate and residual dissolved oxygen as electron
      acceptors. Thus, P and nitrogen (N) removal from wastewater is achieved. During
      the second step, the P enriched biofilm is exposed to a smaller recovery stream
      supplemented with an external carbon source to facilitate P release under
      anaerobic conditions. This allows P to be recovered as a concentrated liquid. The
      EBPR-r process was able to generate a P recovery stream four time more
      concentrated (28 mg-P/L) than the wastewater stream (7 mg-P/L), while removing
      nitrate (denitrification) from the wastewater stream. Repeated exposure of the
      biofilm (10 P-uptake and release cycles) to a recovery stream yielded up to 100
      mg-P/L. Overall, EBPR-r is the first post denitrification strategy that can also
      facilitate P recovery during secondary wastewater treatment.

PMID- 24041528
TI  - Time-course profiling of molecular stress responses to silver nanoparticles in
      the earthworm Eisenia fetida.
AB  - The molecular mechanism of silver nanoparticle (AgNP) toxicity, particularly its
      temporal aspect, is currently limited in the literature. This study seeks to
      identify and profile changes in molecular response patterns over time during soil
      exposure of the earthworm Eisenia fetida to AgNPs (82+/-27 nm) with reference to
      dissolved silver salt (AgNO3). Principal component analysis of selected gene and
      enzyme response profiles revealed dissimilar patterns between AgNO3 and AgNP
      treatments and also over time. Despite the observed difference in molecular
      profiles, the body burdens of total Ag were within the same range (10-40 mg/kg
      dry weight worm) for both treatments with apparent correlation to the induction
      pattern of metallothionein. AgNO3 induced the genes and enzymes related to
      oxidative stress at day 1, after which markers of energy metabolism were all
      suppressed at day 2. Exposure to AgNPs likewise led to induction of oxidative
      stress genes at day 2, but with a temporal pattern shift to immune genes at day
      14 following metabolic upregulation at day 7. The involvement of oxidative stress
      and subsequent alterations in immune gene regulation were as predicted by our in
      vitro study reported previously, highlighting the importance of immunological
      endpoints in nanosilver toxicity.

PMID- 24041529
TI  - Dynamics and residues of mixed formulation of fenamidone and mancozeb in gherkin
      field ecosystem.
AB  - The dynamics and residues of mixed formulation of fenamidone and mancozeb in a
      gherkin field ecosystem were investigated. The quantification was performed using
      gas chromatography-electron capture detection (GC-ECD) and UV-vis
      spectrophotometry for fenamidone and mancozeb residues, respectively. The method
      was validated using blank samples spiked at three levels and the results showed
      that recoveries ranged from 92 to 98 and 90 to 96 percent with relative standard
      deviations (RSD) ranging of 0.78-5.9 and 2.04-4.41 percent for fenamidone and
      mancozeb, respectively. The compound degradation followed a first order kinetics
      with half-lives of 2.8-2.82 and 2.02-2.26 days, for fenamidone and mancozeb,
      respectively. Pesticide residues in fruit were below the EU maximum residue level
      (MRL) after 10 days for fenamidone (0.02 ug/g) and just after treatment for
      mancozeb (2 ug/g). These results can be utilized in formulating the spray
      schedule and safety evaluation for these pesticides in gherkin.

PMID- 24041530
TI  - Optimization of the combined ultrasonic assisted/adsorption method for the
      removal of malachite green by gold nanoparticles loaded on activated carbon:
      experimental design.
AB  - The present study was aimed to experimental design optimization applied to
      removal of malachite green (MG) from aqueous solution by ultrasound-assisted
      removal onto the gold nanoparticles loaded on activated carbon (Au-NP-AC). This
      nanomaterial was characterized using different techniques such as FESEM, TEM,
      BET, and UV-vis measurements. The effects of variables such as pH, initial dye
      concentration, adsorbent dosage (g), temperature and sonication time on MG
      removal were studied using central composite design (CCD) and the optimum
      experimental conditions were found with desirability function (DF) combined
      response surface methodology (RSM). 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 applicability was tested for experimental data and
      the second-order equation and intraparticle diffusion models control the kinetic
      of the adsorption process. The small amount of proposed adsorbent (0.015 g) is
      applicable for successful removal of MG (RE>99%) in short time (4.4 min) with
      high adsorption capacity (140-172 mg g(-1)).

PMID- 24041531
TI  - Vibrational and electronic spectroscopic studies of melatonin.
AB  - We report the infrared absorption and Raman spectra of melatonin recorded with
      488 and 632.8 nm excitations in 3600-2700 and 1700-70 cm(-1) regions. Further, we
      optimized molecular structure of the three conformers of melatonin within density
      functional theory calculations. Vibrational frequencies of all three conformers
      have also been calculated. Observed vibrational bands have been assigned to
      different vibrational motions of the molecules on the basis of potential energy
      distribution calculations and calculated vibrational frequencies. Observed band
      positions match well with the calculated values after scaling except NH
      stretching mode frequencies. It is found that the observed and calculated
      frequencies mismatch of NH stretching is due to intermolecular interactions
      between melatonin molecules.

PMID- 24041532
TI  - Structural, vibrational and theoretical studies of anilinium trichloroacetate:
      new hydrogen bonded molecular crystal with nonlinear optical properties.
AB  - In this work, we report a combined experimental and theoretical study on
      molecular structure, vibrational spectra and NBO analysis of the potential
      nonlinear optical (NLO) material anilinium trichloroacetate. The FT-IR and FT
      Raman spectra of the compound have been recorded together between 4000-80 cm(-1)
      and 3600-80 cm(-1) regions, respectively. The compound crystallizes in the
      noncentrosymmetric space group of monoclinic system. The optimized molecular
      structure, vibrational wavenumbers, IR intensities and Raman activities have been
      calculated by using density functional method (B3LYP) with 6-311++G(d,p) as
      higher basis set. The obtained vibrational wavenumbers and optimized geometric
      parameters were seen to be in good agreement with the experimental data. DSC
      measurements on powder samples do not indicate clearly on the occurrence of phase
      transitions in the temperature 113-293 K. The Kurtz and Perry powder reflection
      technique appeared to be very effective in studies of second-order nonlinear
      optical properties of the molecule. The non-linear optical properties are also
      addressed theoretically. The predicted NLO properties of the title compound are
      much greater than ones of urea. In addition, DFT calculations of the title
      compound, molecular electrostatic potential, frontier orbitals and thermodynamic
      properties were also performed at 6-311++G(d,p) level of theory. For title
      crystal the SHG efficiency was estimated by Kurtz-Perry method to be d(eff)=0.70
      d(eff) (KDP).

PMID- 24041533
TI  - The impact of surface loading and dosing scheme on the skin uptake of fragrances.
AB  - This study compared the skin uptake of gamma-undecalactone, decanol, and dodecyl
      acetate in an in vitro, un-occluded penetration assay in which they were applied
      to porcine skin at different finite loadings and application schemes. The pattern
      of fractional uptake differed between the chemicals and did not show the often
      assumed inverse correlation with surface loading. Furthermore, the mass uptake of
      identical cumulative amounts of the chemicals was not always additive. These
      results show that the uptake of fragrances in absence of occlusion and at finite
      loadings is chemical-specific and depends on the surface loading, the application
      scheme, and most probably, on the effects of the chemicals on the skin barrier
      efficiency. The observed lack of additivity might explain some of the differences
      in the responses observed in patch and repeated open application tests, and the
      boosting of the allergic state in sensitized individuals by sub-clinical
      exposures. 

PMID- 24041534
TI  - A screen for apoptotic synergism between clinical relevant nephrotoxicant and the
      cytokine TNF-alpha.
AB  - Nephrotoxicity remains one of the main reasons for post-market drug withdrawal.
      Tumour necrosis factor alpha (TNF-alpha) secretion has been shown to underlie the
      nephrotoxicity induced by some of these drugs. Yet, there is currently no
      reliable and sensitive in vitro assay available to screen for nephrotoxicants of
      which toxicity largely depends on TNF-alpha secretion. Therefore, we developed
      and applied a sensitive fluorescence-based in vitro assay for TNF-alpha-mediated
      nephrotoxicity screening using mouse immortalized proximal tubular epithelial
      cells (IM-PTECs). Our assay allows rapid evaluation of TNF-alpha-mediated
      toxicant-induced apoptosis and necrosis using fixed endpoint and live cell
      measurements. To evaluate our assay, sixteen nephrotoxicants and two control non
      nephrotoxicants were used. Out of the sixteen nephrotoxicants, eight induced cell
      death, of which five induced apoptosis as well as necrosis. Moreover, TNF-alpha
      significantly enhanced apoptotic cell death induced by cisplatin, cyclosporine A,
      tacrolimus and azidothymidine. These nephrotoxicants are known to induce
      inflammation in vivo which has been linked to an enhancement of nephrotoxicity
      for cisplatin, cyclosporine A and tacrolimus, confirming the functionality of our
      assay. Overall, our assay allows rapid and sensitive measurement of apoptosis and
      necrosis induced by a combination of nephrotoxicants and inflammatory components
      such as TNF-alpha and can be used as an alternative assay for nephrotoxicity
      prediction in vitro. 

PMID- 24041535
TI  - A method for the assessment of DNA damage in individual, one day old, zebrafish
      embryo (Danio rerio), without prior cell isolation.
AB  - Zebrafish (Danio rerio) embryos are increasingly used as an experimental model in
      toxicology for the detection of lethal and sub-lethal effects of diverse
      chemicals. DNA damage, an early biomarker of long-term effects such as
      mutagenesis and carcinogenesis, is commonly assessed in vitro and in vivo using
      the comet assay - single cell gel electrophoresis. Here we describe a new rapid
      method for the detection of DNA strand breaks in individual, one day old,
      zebrafish embryos, without the need for prior cell isolation. After the completed
      spawning, the embryos were exposed to non-toxic concentrations of model genotoxic
      compounds for 24h. The embryos were then treated with Pronase E, embedded on
      microscope slides and squashed to release the cells. After alkaline
      electrophoresis, the nuclei were stained with ethydium bromide and analyzed by
      fluorescence microscopy. Preparation of slides by the described method resulted
      in well separated cell nuclei with low background DNA damage. A significant
      increase in DNA damage was detected after exposure to the model genotoxic
      compounds, methylmethan sulphonate (MMS) and benzo(a)pyrene (BaP), while no DNA
      damage was induced by NaCl. Our method proved to be sensitive and suitable for
      the detection of DNA damage in one day old zebrafish embryos, suggesting it could
      serve as a useful tool for monitoring the genotoxic potential of chemicals and
      environmental pollutants. 

PMID- 24041536
TI  - Imaging atrial arrhythmic intracellular calcium in intact heart.
AB  - Abnormalities in intracellular Ca(2+) signaling have been proposed to play an
      essential role in the pathophysiology of atrial arrhythmias. However, a direct
      observation of intracellular Ca(2+) in atrial myocytes during atrial arrhythmias
      is lacking. Here, we have developed an ex vivo model of simultaneous Ca(2+)
      imaging and electrocardiographic recording in cardiac atria. Using this system we
      were able to record atrial arrhythmic intracellular Ca(2+) activities. Our
      results indicate that atrial arrhythmias can be tightly linked to intracellular
      Ca(2+) waves and Ca(2+) alternans. Moreover, we applied this strategy to analyze
      Ca(2+) signals in the hearts of WT and knock-in mice harboring a 'leaky' type 2
      ryanodine receptor (RyR2-R2474S). We showed that sarcoplasmic reticulum (SR)
      Ca(2+) leak increases the susceptibility to Ca(2+) alternans and Ca(2+) waves
      increasing the incidence of atrial arrhythmias. Reduction of SR Ca(2+) leak via
      RyR2 by acute treatment with S107 reduced both Ca(2+) alternans and Ca(2+) waves,
      and prevented atrial arrhythmias. 

PMID- 24041537
TI  - Beta-adrenergic-stimulated L-type channel Ca2+ entry mediates hypoxic Ca2+
      overload in intact heart.
AB  - Ca(2+) mishandling plays a key role in ischemia- and hypoxia-related cardiac
      dysfunction and injury. However, the cellular and molecular mechanisms underlying
      hypoxic intracellular Ca(2+) ([Ca(2+)]i) overload remain incompletely understood.
      This study aimed to investigate possible mechanisms of [Ca(2+)]i overload during
      hypoxia in the intact heart. In Langendorff-perfused heart expressing the Ca(2+)
      indicator GCaMP2, confocal microscopy was used to simultaneously visualize
      [Ca(2+)]i, mitochondrial membrane potential (DeltaPsim, by tetramethylrhodamine
      methyl ester) and sarcolemmal integrity (by Evans blue). Upon hypoxia (pO2 ~20
      mmHg in glucose-free perfusate), [Ca(2+)]i transients were initially enhanced and
      then became depressed, arrhythmic, and completely abolished within 12 min. At ~20
      min, basal [Ca(2+)]i rose to its first peak at a supraphysiological level,
      coincident with loss of DeltaPsim and onset of rigor. A greater [Ca(2+)]i rise
      occurred at ~2h and was linked to the loss of sarcolemmal integrity. Removal of
      extracellular Ca(2+) or blockade of the l-type Ca(2+) channel (LTCC) (10 MUM
      diltiazem or nifedipine) prevented [Ca(2+)]i overload and markedly delayed the
      loss of DeltaPsim; by contrast, depletion of the sarcoplasmic reticulum Ca(2+)
      store by thapsigargin did not have any significant effect. Importantly, beta
      adrenergic blockade or depletion of the sympathetic catecholamine store by
      reserpine slowed the Ca(2+) and mitochondrial responses to hypoxia in intact
      heart. This LTCC-mediated hypoxic [Ca(2+)]i overload was reproduced in isolated
      cardiomyocytes when beta-adrenergic agonist was present. Taken together, we
      conclude that Ca(2+) entry through beta-adrenergic-stimulated LTCC underlies
      hypoxia-induced [Ca(2+)]i overload and the ensuing loss of mitochondrial function
      in intact heart.

PMID- 24041538
TI  - Effects of angiotensin (5-8) microinfusions into the ventrolateral periaqueductal
      gray on defensive behaviors in rats.
AB  - Peptides of the renin-angiotensin system modulate blood pressure and hydro
      electrolyte composition. Angiotensin (Ang) receptors are localized in brain areas
      related to the regulation of autonomic and endocrine control and involved in
      sensory perception, memory process and behavioral responses. Among these areas,
      the ventrolateral periaqueductal gray (vlPAG) is one of the most important
      structures of the neuronal circuitry controlling the autonomic and behavioral
      components of emotional states. Although Ang II metabolism in the vlPAG forms
      several Ang-peptides including Ang (5-8), the role of this tetrapeptide in the
      organization of defensive responses has not yet been described. To address this
      issue, the purpose of the present study was to determine the effects of intra
      vlPAG injections of Ang (5-8) (0.2, 0.4 and 0.8 nmol/0.25 MUL) in rats submitted
      to the elevated plus-maze (EPM) test. Additionally, it was evaluated the effects
      of intra-vlPAG Ang (5-8) on the expression of conditioned fear, assessed by the
      fear-potentiated startle and contextual conditioned freezing tests. The results
      showed that Ang (5-8) produced an intense, dose-related reduction in the entries
      into and time spent in the open arms of the EPM, decreased direct exploration and
      increased risk assessment behaviors. Moreover, intra-vlPAG injections of Ang (5
      8) before the test session promoted pro-aversive effects in the FPS and enhanced
      contextual freezing. Taken together, these results point out to an important
      anxiogenic-like action for Ang (5-8) in the mediation of defensive behaviors
      organized in the vlPAG.

PMID- 24041539
TI  - The temporal evolution of antidrug antibodies in patients with inflammatory bowel
      disease treated with infliximab.
AB  - OBJECTIVE: To characterise the temporal evolution of antibodies to infliximab
      (ATI). DESIGN: Prospective observational study of infliximab-treated patients
      with inflammatory bowel disease between 2009 and 2012. INTERVENTIONS: Trough
      levels of infliximab and ATI were measured before each infusion by anti-lambda
      ELISA. Patients were monitored for disease activity by clinical activity indexes
      and for dose-intensification or infliximab cessation. The occurrence of transient
      ATI disappearing spontaneously without intervention was recorded separately.
      RESULTS: 125 patients were included (98 Crohn's disease, 27 ulcerative colitis,
      median follow-up 11.5+/-22 months) and 1119 sera were analysed for infliximab and
      ATI levels. Kaplan-Meier analysis showed that 42% of patients remained ATI-free
      by 4 years of treatment. Most (90%) of the patients who developed ATI did so
      within the first 12 months of therapy, whereas transient ATI were detected
      throughout the duration of infliximab therapy (p<0.001). ATI incidence was
      similar between patients who received infliximab previously (episodic/interrupted
      therapy patients, n=14) and scheduled-therapy patients (n=111). In the scheduled
      group, combination immunomodulator+infliximab resulted in longer ATI-free
      survival compared with monotherapy (p=0.003, logrank test). Survival free of
      clinical loss of response was enjoyed by 51% of patients, and serial measurements
      showed that ATI development often preceded the onset of clinical flare.
      CONCLUSIONS: When followed prospectively, most patients who develop ATI do so
      within the first 12 months of therapy. This incidence is reduced by concomitant
      immunomodulator even in scheduled-therapy patients. In contrast, transient ATI,
      which are of little clinical significance, can appear haphazardly at any time
      during treatment. The onset of clinical loss of response may lag behind the
      appearance of anti-infliximab antibodies.

PMID- 24041540
TI  - Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation
      and diarrhoea predominant irritable bowel syndrome.
AB  - OBJECTIVE: The complex genetic aetiology underlying irritable bowel syndrome
      (IBS) needs to be assessed in large-scale genetic studies. Two independent IBS
      cohorts were genotyped to assess whether genetic variability in immune, neuronal
      and barrier integrity genes is associated with IBS. DESIGN: 384 single nucleotide
      polymorphisms (SNPs) covering 270 genes were genotyped in an exploratory cohort
      (935 IBS patients, 639 controls). 33 SNPs with Puncorrected<0.05 were validated
      in an independent set of 497 patients and 887 controls. Genotype distributions of
      single SNPs were assessed using an additive genetic model in IBS and clinical
      subtypes, IBS-C and IBS-D, both in individual and combined cohorts. Trait anxiety
      (N=614 patients, 533 controls), lifetime depression (N=654 patients, 533
      controls) and mRNA expression in rectal biopsies (N=22 patients, 29 controls)
      were correlated with SNP genotypes. RESULTS: Two SNPs associated independently in
      the exploratory and validation cohort: rs17837965-CDC42 with IBS-C
      (ORexploratory=1.59 (1.05 to 1.76); ORvalidation=1.76 (1.03 to 3.01)) and
      rs2349775-NXPH1 with IBS-D (ORexploratory=1.28 (1.06 to 1.56); ORvalidation=1.42
      (1.08 to 1.88)). When combining both cohorts, the association of rs2349775
      withstood post hoc correction for multiple testing in the IBS-D subgroup.
      Additionally, three SNPs in immune-related genes (rs1464510-LPP, rs1881457-IL13,
      rs2104286-IL2RA), one SNP in a neuronal gene (rs2349775-NXPH1) and two SNPs in
      epithelial genes (rs245051-SLC26A2, rs17837965-CDC42) were weakly associated with
      total-IBS (Puncorrected<0.05). At the functional level, rs1881457 increased IL13
      mRNA levels, whereas anxiety and depression scores did not correlate with
      rs2349775-NXPH1. CONCLUSIONS: Rs2349775 (NXPH1) and rs17837965 (CDC42) were
      associated with IBS-D and IBS-C, respectively, in two independent cohorts.
      Further studies are warranted to validate our findings and to determine the
      mechanisms underlying IBS pathophysiology.

PMID- 24041541
TI  - Kinetic study on nitrogen removal performance in marine anammox bacterial
      culture.
AB  - Kinetics of anaerobic ammonium oxidation (anammox) reaction in marine anammox
      bacterial culture was first investigated. The nitrogen removal performance of the
      reactor was compared with prediction of Monod model, modified Stover-Kincannon
      model, first-order and the Grau second-order substrate removal models. Based on
      calculations, Monod model, modified Stover-Kincannon model and the Grau second
      order model proved to be more appropriate to describe the nitrogen removal
      kinetics of the reactor than first-order model with high determination
      coefficients of 0.993, 0.993 and 0.991, respectively. According to the modified
      Stover-Kincannon model, the maximal substrate removal rate (rm) and saturation
      rate constant (KB) were suggested as 7.37 and 6.41 g N/L/d, respectively. In
      addition, in light of the Monod model, the saturation concentration (Ks) and the
      maximal specific substrate removal rate constant (Rm) were determined to be 0.107
      g/L and 0.952 g N/g MLVSS/d, respectively. Moreover, model evaluation was carried
      out by assessing the linear correlation between measured and predicted values.
      Both kinetics study and model evaluation showed that Monod model, modified Stover
      Kincannon model and the Grau second-order substrate removal models could be used
      to describe the kinetic behavior or design of the marine anammox reactor.

PMID- 24041542
TI  - Enrichment of a microbial consortium capable of reductive deiodination of 2,4,6
      triiodophenol.
AB  - An anaerobic microbial consortium capable of reductively dehalogenating 2,4,6
      triiodophenol (2,4,6-TIP) to 4-iodophenol was enriched from sediments collected
      from an iodine-producing industry, Chiba, Japan. In the presence of lactate, the
      enrichment reductively deiodinated 2,4,6-TIP, 2,4-diiodophenol and 2-iodophenol,
      suggesting preferential removal of ortho-substituted iodines. PCR-denaturing
      gradient gel electrophoresis and 16S rRNA gene sequence analysis showed that at
      least 4 bacteria, including Pseudomonas stutzeri, Clostridium sp.,
      Sedimentibacter sp., and unidentified Chloroflexi bacterium, were predominant in
      the enrichment. Interestingly, the DGGE band corresponding to the Chloroflexi
      bacterium disappeared when the enrichment was grown in the absence of 2,4,6
      triiodophenol. In addition, the DGGE band with a nearly identical gene sequence
      was detected in another enrichment that consumed 3-amino-2,4,6-triiodobenzoic
      acid (ATBA). Phylogenetic analysis of 1416 bp of 16S rRNA gene sequence for this
      putative deiodinating bacterium revealed that it was closely related (93%
      sequence similarity) with an anaerobic bacterium MO-CFX2 belonging to the class
      Anaerolineae, which was recently isolated from subseafloor sediments. The
      sequence similarities with other known reductive dehalogenating bacteria such as
      Dehalococcoides mccartyi and Dehalobium chlorocoercia were relatively low (78%
      80%). Quantitative PCR analysis targeting specific 16S rRNA gene region of the
      putative deiodinating bacterium showed that the enrichments consuming 2,4,6-TIP
      or ATBA contained 18 to 1070 times much higher amounts of 16S rRNA gene copies
      than those in the enrichments that do not consume these iodoaromatic compounds.
      These results suggest that a novel anaerobic bacterium in the class Anaerolineae
      is capable of reductively deiodinating 2,4,6-iodobenzene derivatives.

PMID- 24041543
TI  - Marine metaproteomics: current status and future directions.
AB  - Metaproteomics is a new field within the 'omics' science which investigates
      protein expression from a complex biological system and provides direct evidence
      of physiological and metabolic activities. Characterization of the metaproteome
      will enhance our understanding of the microbial world and link microbial
      communities to ecological functions. Recently, the availability of extensive
      metagenomic sequences from various marine microbial communities has extended the
      postgenomic era to the field of oceanography. Although still in its infancy,
      metaproteomics has shown its powerful potential with regard to functional gene
      expression within microbial habitats and their interactions with the ambient
      environment as well as their biogeochemical functions. However, the application
      of metaproteomic approaches to complex marine samples still faces considerable
      challenges. This review summarizes the recent progress in marine metaproteomics
      and discusses the limitations of and perspectives for this approach in the study
      of the marine ecosystem. This article is part of a Special Issue entitled: Trends
      in Microbial Proteomics. 

PMID- 24041544
TI  - Cortisol awakening response in late pregnancy in women with previous or ongoing
      depression.
AB  - Pregnancy is associated with increased basal cortisol levels, and decreased
      hypothalamic-pituitary-adrenal (HPA) axis reactivity. The cortisol awakening
      response (CAR) is a measure of HPA-axis reactivity which has been reported to be
      increased in patients with ongoing depressive disorder and in individuals with
      remitted depression. In this study, we investigated HPA-axis reactivity in
      pregnant women with ongoing or previous depression. The CAR was assessed by
      measurement of salivary cortisol at awakening and 15, 30, and 45 min post
      awakening. Based on structured psychiatric interviews and repeated measurements
      of depressive symptoms during pregnancy, 134 women were included in one of the
      three groups: never depressed (n=57), depressed prior to the current pregnancy
      (n=39), and depressed during the current pregnancy (n=38). Given the prior
      findings of increased CAR in non-pregnant depressed subjects, we hypothesized
      that an ongoing or previous depression would result in a higher CAR. Contrary to
      our hypothesis, a mixed models analysis failed to yield significant group
      differences. Thus, our results suggest that never depressed pregnant women and
      women with depression during pregnancy have similar cortisol awakening responses.
      Furthermore, our findings suggest that the cortisol awakening response does not
      differ between currently healthy women with and without experience of a
      depressive episode during late pregnancy.

PMID- 24041545
TI  - Survey of poliovirus antibodies in Kano, Northern Nigeria.
AB  - INTRODUCTION: In 1988, the World Health Assembly resolved to eradicate
      poliomyelitis. Since then, much progress towards this goal has been made, but
      three countries including Nigeria remain polio-endemic as of end 2012. To assess
      the immunity level against poliomyelitis in young children in Northern Nigeria,
      we conducted a seroprevalence survey in the Kano Metropolitan Area (KMA) in May
      2011. METHODS: Parents or guardians of infants aged 6-9months or children aged 36
      47months presenting to the outpatient department of Murtala Mohammad Specialist
      Hospital were approached for participation, screened for eligibility and were
      asked to provide informed consent. After that, a questionnaire was administered
      and blood was collected for neutralization assay. RESULTS: A total of 327
      subjects were enrolled. Of these, 313 (96%) met the study requirements and were
      analyzed (161 [51%] aged 6-9months and 152 [49%] aged 36-47months). Among
      subjects aged 6-9months, seroprevalence was 81% (95% confidence interval [CI] 75
      87%) to poliovirus type 1, 76% (95% CI 68-81%) to poliovirus type 2, and 73% (95%
      CI 67-80%) to poliovirus type 3. Among subjects aged 36-47months, the
      seroprevalence was 91% (95% CI 86-95%) to poliovirus type 1, 87% (95% CI 82-92%)
      for poliovirus type 2, and 86% (95% CI 80-91%) to poliovirus type 3.
      Seroprevalence was associated with history of oral poliovirus vaccine (OPV)
      doses, maternal education and gender. CONCLUSIONS: Seroprevalence is lower than
      required levels for poliovirus interruption in the KMA. Persistence of immunity
      gaps in the 36-47months group is a big concern. Since higher number of vaccine
      doses is associated with higher seroprevalence, it implies that failure-to
      vaccinate and not vaccine failure accounts for the suboptimal seroprevalence.
      Intensified efforts are necessary to administer polio vaccines to all target
      children and surpass the threshold levels for herd immunity.

PMID- 24041546
TI  - Capillary rise dynamics of aqueous glycerol solutions in glass capillaries: a
      critical examination of the Washburn equation.
AB  - The classic description of capillary rise given by the Washburn equation was
      recently questioned in the light of experimental evidence for a velocity
      dependent dynamic contact angle at a moving contact line. We present a systematic
      investigation of the capillary rise dynamics of glycerol and aqueous glycerol
      solutions in vertical glass capillaries of various radii. For pure glycerol, the
      results of our experiments are in almost perfect agreement with the predictions
      of the Washburn equation using independently measured values for the liquid and
      capillary parameters. For aqueous glycerol solutions we observe discrepancies
      between the theoretical expectations and the experimental results, which are
      increasing with the water content of the solution. A thorough analysis, combined
      with scaling arguments, allows us to conclude that dynamic contact angle effects
      alone cannot provide a consistent explanation for these discrepancies. Rather,
      they can be perfectly accounted for if the mixture flowing in the capillary would
      have an effective, increased viscosity (in respect to the nominal value). We
      suggest and briefly discuss various mechanisms that could contribute to this
      observed behavior. 

PMID- 24041547
TI  - Photochemical grafting of methyl groups on a Si(111) surface using a Grignard
      reagent.
AB  - The photochemical grafting of methyl groups onto an n-type Si(111) substrate was
      successfully achieved using a Grignard reagent. The preparation involved
      illuminating a hydrogen-terminated Si(111) that was immersed in a CH3MgBr-THF
      solution. The success was attributed to the ability of the n-type hydrogenated
      substrate to produce holes on its surface when illuminated. The rate of grafting
      methyl groups onto the silicon surface was higher when a larger illumination
      intensity or when a substrate with lower dopant concentration was used. In
      addition, the methylated layer has an atomically flat structure, has a
      hydrophobic surface, and has electron affinity that was lower than the bulk Si. 

PMID- 24041548
TI  - Metal deposition by electroless plating on polydopamine functionalized micro- and
      nanoparticles.
AB  - A novel approach for the fabrication of metal coated micro- and nanoparticles by
      functionalization with a thin polydopamine layer followed by electroless plating
      is reported. The particles are initially coated with polydopamine via self
      polymerization. The resulting polydopamine coated particles have a surface rich
      in catechols and amino groups, resulting in a high affinity toward metal ions.
      Thus, they provide an effective platform for selective electroless metal
      deposition without further activation and sensitization steps. The combination of
      a polydopamine-based functionalization with electroless plating ensures a simple,
      scalable, and cost-effective metal coating strategy. Silver-plated tungsten
      carbide microparticles, copper-plated tungsten carbide microparticles, and copper
      plated alumina nanoparticles were successfully fabricated, showing also the high
      versatility of the method, since the polymerization of dopamine leads to the
      formation of an adherent polydopamine layer on the surface of particles of any
      material and size. The metal coated particles produced with this process are
      particularly well suited for the production of metal matrix composites, since the
      metal coating increases the wettability of the particles by the metal, promoting
      their integration within the matrix. Such composite materials are used in a
      variety of applications including electrical contacts, components for the
      automotive industries, magnets, and electromagnetic interference shielding. 

PMID- 24041549
TI  - Controlled fabrication of PANI/CNF hybrid films: molecular interaction induced
      various micromorphologies and electrochemical properties.
AB  - In this paper, a facile and efficient method is reported to prepare
      polyaniline/carbon nanofiber (PANI/CNF) hybrid films by in situ chemical
      polymerization of aniline. The various morphologies and microstructures of
      PANI/CNF hybrid films can be controlled by adjusting the concentration of aniline
      and different acids as the protonation reagent, and the formation mechanism is
      illustrated in this study. The surface morphologies and chemical structure of the
      PANI/CNF hybrid films are characterized by scanning electron microscope (SEM),
      transmission electron microscope (TEM), water contact angle (CA), FT-IR, Raman,
      and UV-vis spectrophotometers. The different morphology of uniformly coated,
      twist-tangled, and needle-like PANI built on CNF films are obtained by using HCl,
      H2SO4, and HClO4 as protonation reagent and the obtained hybrid films are labeled
      as PANI/CNF-f1, PANI/CNF-f2, and PANI/CNF-f3, respectively. We demonstrated that
      the different protonation reagent has the determined effect on the surface
      properties of the obtained hybrid films that can transfer from hydrophilic to
      hydrophobic. Besides, the various morphologies of PANI play an important role in
      their electrochemical properties. PANI/CNF-f3 exhibits higher specific
      capacitance and better stability than that of the PANI/CNF-f1 and PANI/CNF-f2.
      Considering its unique needle-like structure, this work is a proof of concept
      that micro-structure and morphology can determine the macro-properties. And this
      study supplies a facile method to fabricate PANI/CNF hybrid films that can be
      used as electrode materials in supercapacitors. 

PMID- 24041550
TI  - Uptake and retention of amitriptyline by kaolinite.
AB  - As the most commonly prescribed tricyclic antidepressant, amitriptyline (AT) is
      frequently detected in wastewater, surface runoff, and effluents from sewage
      treatment plants, and could potentially reach agriculture land through the
      application of municipal biosolids or reclaimed water. Kaolinite is one of the
      most important soil components under warm and humid climate conditions. In this
      study, the uptake and retention of AT by kaolinite from aqueous solution were
      investigated by batch tests, XRD, and FTIR analyses. The uptake of AT on
      kaolinite was instantaneous, attributed to surface adsorption as confirmed by XRD
      analyses. Quantitative correlation between desorption of exchangeable cations and
      AT adsorption confirmed experimentally that cation exchange was the dominant
      mechanism of AT uptake on kaolinite. The values for free energy of adsorption
      also suggested physi-sorption such as cation exchange. Solution pH had minimal
      influence at pH 5-11 even though the pKa value of AT was 9.4 and the surface
      charge of kaolinite was pH-dependent. 

PMID- 24041551
TI  - First identification of KPC-2 and VIM-1 producing Klebsiella pneumoniae in
      Bulgaria.

PMID- 24041552
TI  - Improved diagnosis of melioidosis using a 2-dimensional immunoarray.
AB  - Melioidosis is caused by the Gram negative bacterium Burkholderia pseudomallei.
      The gold standard for diagnosis is culture, which requires at least 3-4 days
      obtaining a result, hindering successful treatment of acute disease. The existing
      indirect haemagglutination assay (IHA) has several disadvantages, in that
      approximately half of patients later confirmed culture positive are not diagnosed
      at presentation and a subset of patients are persistently seronegative. We have
      developed 2 serological assays, an enzyme-linked immunosorbent assay (ELISA), and
      a 2-dimensional immunoarray (2DIA), capable of detecting antibodies in patient
      sera from a greater proportion of IHA-negative patient subsets. The 2DIA format
      can distinguish between different LPS serotypes. Currently, the 2DIA has a
      sensitivity and specificity of 100% and 87.1%, respectively, with 100% of culture
      positive, IHA-negative samples detected. The ELISA has a sensitivity and
      specificity of 86.2% and 93.5%, respectively, detecting 67% of culture-positive,
      IHA-negative samples. The ELISA and 2DIA tests described here are more rapid and
      reliable for serological testing compared to the existing IHA. 

PMID- 24041553
TI  - Real-time PCR detection of Mycoplasma pneumoniae in respiratory specimens.
AB  - A real-time PCR assay targeting the phosphotransferase system I gene (ptsI) of
      Mycoplasma pneumoniae was compared to 2 commercially available PCR assays
      targeting the P1 cytadhesion gene (the LightMix(r)Kit Mycoplasma pneumoniae [TIB
      MOLBIOL, Adelphia, NJ, USA] and M. pneumoniae Analyte Specific Reagent [Focus
      Diagnostics, Cypress, CA, USA] assays) and to a PCR assay targeting the M.
      pneumoniae repetitive element, RepMP1. Thirty previously positive specimens
      including 15 throat swab, 10 bronchoalveolar lavage, and 5 sputum specimens, all
      tested positive with the ptsI and M. pneumoniae ASR assays. Among the previously
      positive specimens, 14/15 throat swab, 9/10 bronchoalveolar lavage, and 4/5
      sputum specimens tested positive with the LightMix(r)Kit Mycoplasma pneumoniae
      assay and 13/15 throat swab, 10/10 bronchoalveolar lavage, and 4/5 sputum
      specimens tested positive with the RepMP1 assay. Forty previously negative
      clinical specimens tested negative using the ptsI assay. A PCR assay targeting M.
      pneumoniae ptsI performs equivalently to assays targeting the P1 cytadhesion gene
      or RepMP1. 

PMID- 24041554
TI  - Evaluation of Etest(r) strips for detection of KPC and metallo-carbapenemases in
      Enterobacteriaceae.
AB  - The performance of Etest KPC and MBL strips (bioMerieux) was evaluated as
      compared to other phenotypic tests for detecting carbapenemases of the KPC-type
      and metallo-beta-lactamases, respectively, on 133 well-characterized
      enterobacterial isolates. KPC and meropenem-containing MP/MPI Etest had high
      sensitivity (>92 %) and specificity (>97 %). 

PMID- 24041555
TI  - Short-term outcomes for robotic colorectal surgery by provider volume.
AB  - BACKGROUND: There has been a rapid increase in robotic colorectal surgery.
      Benefits of this technology are unclear and being investigated. However,
      differences in outcomes between centers have not been evaluated. Our aim was to
      evaluate outcomes for robotic colorectal procedures by surgeon and hospital
      volume. STUDY DESIGN: A national inpatient database was reviewed for robotic
      colorectal resections performed during an 18-month period. Hospitals and surgeons
      were stratified into high, average, and low case volumes based on a normal
      distribution scale. High, average, and low volume was defined as <= 10, 11 to 20,
      and >20, respectively, for hospitals, and <= 5, 6 to 15, and >15, respectively,
      for surgeons. Short-term outcomes and hospital cost were evaluated. RESULTS:
      There were 1,428 robotic colorectal cases across 123 hospitals and 411 surgeons
      evaluated. Only 13% (n = 16) of hospitals and 4.4% (n = 18) of surgeons performed
      a high volume of robotic colorectal cases. Lower volume was associated with
      significantly more overall complications (p < 0.001; p < 0.001), longer length of
      stay (p = 0.005; p < 0.001), and higher cost (p < 0.001; p < 0.001) at the
      hospital and surgeon level, respectively. High-volume hospitals and surgeons had
      significantly lower rates of postoperative bleeding (p < 0.001; p < 0.001) and
      ileus (p = 0.003; p = 0.0014). CONCLUSIONS: Lower-volume providers, who are
      performing the majority of procedures, are generating more complications, longer
      hospital lengths of stay, and higher costs of care. These results have a negative
      impact on quality outcomes measures for those facilities. Although surgeons and
      hospitals continue to selectively explore robotics, this should be limited to
      high volume and interested surgeons and hospitals to offer high-quality outcomes
      to patients.

PMID- 24041556
TI  - American College of Surgeons NSQIP: quality in-training initiative pilot study.
AB  - BACKGROUND: Clinical outcomes data are playing an increasingly important role in
      medical decision-making, reimbursement, and provider evaluation, but there are no
      documented programs that provide outcomes data to surgical residents as part of a
      structured curriculum. Our objectives were to develop a national collaborative of
      training programs to unify the efforts between quality and education personnel
      and demonstrate the feasibility of generating customized reports of patient
      outcomes for use in surgical education. STUDY DESIGN: The pool of potential
      hospitals was evaluated by comparing ACS NSQIP participants with the roster of
      clinical sites for general surgery residency programs maintained by FREIDA
      Online. A program and user guide was developed to generate custom reports based
      on institutional data, and a voluntary pilot was conducted, consisting of initial
      development, implementation, and feedback stages. Programs that successfully
      completed installation and report generation were queried for feedback on time
      and resources used. RESULTS: Of 245 general surgery residency programs, 47% had a
      NSQIP-affiliated sponsor institution, and an additional 31% had at least 1 NSQIP
      affiliated participant institution. Sixty general surgery residency programs have
      expressed interest in collaboration. Seventeen pilot sites completed training and
      installation, and were able to independently generate custom reports. The
      response rate for the post-report survey was 50%. Participants reported that
      training and installation typically required one 2-hour phone call, and that
      total time devoted to the project was less than 8 hours. CONCLUSIONS:
      Collaboration between educators and quality improvement personnel from a diverse
      group of organizations to integrate outcomes data into surgical education is
      feasible. Obtaining resident and team reports from ACS NSQIP can be done with
      minimal effort. Future efforts will be aimed at developing a national data
      centered curriculum for general surgery programs.

PMID- 24041557
TI  - Referral patterns and treatment choices for patients with hepatocellular
      carcinoma: a United States population-based study.
AB  - BACKGROUND: Patterns of care of physician specialists may differ for patients
      with hepatocellular carcinoma (HCC). Reasons underlying variations are poorly
      understood. One source of variation may be disparate referral rates to
      specialists, leading to differences in cancer-directed treatments. STUDY DESIGN:
      Surveillance, Epidemiology, and End Results (SEER)-linked Medicare database was
      queried for patients with HCC, diagnosed between 1998 and 2007, who consulted 1
      or more physicians after diagnosis. Visit and procedure records were abstracted
      from Medicare billing records. Factors associated with specialist consult and
      subsequent treatment were examined. RESULTS: There were 6,752 patients with HCC
      identified; 1,379 (20%) patients had early-stage disease. Median age was 73
      years; the majority were male (66%), white (60%), and from the West region (56%).
      After diagnosis, referral to a specialist varied considerably
      (hepatology/gastroenterology, 60%; medical oncology, 62%; surgery, 56%;
      interventional radiology [IR], 33%; radiation oncology, 9%). Twenty-two percent
      of patients saw 1 specialist; 39% saw 3 or more specialists. Time between
      diagnosis and visitation with a specialist varied (surgery, 37 days vs IR, 55
      days; p = 0.04). Factors associated with referral to a specialist included
      younger age (odds ratio [OR] 2.16), Asian race (OR 1.49), geographic region
      (Northeast OR 2.10), and presence of early-stage disease (OR 2.21) (all p <
      0.05). Among patients with early-stage disease, 77% saw a surgeon, while 50% had
      a consultation with medical oncologist. Receipt of therapy among patients with
      early-stage disease varied (no therapy, 30%; surgery, 39%; IR, 9%; chemotherapy,
      23%). Factors associated with receipt of therapy included younger age (OR 2.48)
      and early-stage disease (OR 2.20). CONCLUSIONS: After HCC diagnosis, referral to
      a specialist varied considerably. Both clinical and nonclinical factors were
      associated with consultation. Disparities in referral to a specialist and
      subsequent therapy need to be better understood to ensure all HCC patients
      receive appropriate care.

PMID- 24041558
TI  - Morbid obesity and diverticulitis: results from the ACS NSQIP dataset.
AB  - BACKGROUND: We examined the relationship between morbid obesity, clinical
      presentation, and perioperative outcomes in patients offered surgery for
      diverticulitis. STUDY DESIGN: We queried the ACS NSQIP dataset from 2005 to 2010
      for patients undergoing surgery for nonhemorrhaging diverticulitis. Univariate
      comparisons were made between normal weight (NL) and morbidly obese (MO) patients
      in terms of demographics, clinical presentation, and perioperative and
      postoperative outcomes variables using chi-square or rank tests. Multivariable
      regression was used to adjust for age in assessing the impact of MO on the
      likelihood of emergent surgery (ES), ostomy creation, open surgery, and
      undergoing procedures without an anastomosis. RESULTS: We identified 10,952
      patients undergoing surgery for diverticulitis; morbidly obese (body mass index
      [BMI] >= 40 kg/m(2), n = 592, 5.7%), normal weight (BMI 18.5 to 25 kg/m(2), n =
      2,530, 24.2%). Morbidly obese patients were younger than NL patients by an
      average of 9.4 years (p < 0.001). Morbidly obese patients underwent ES more
      frequently than NL patients (19.3% vs 15.4%; p = 0.025). Multivariable regression
      identified morbid obesity as an independent risk factor for ES (odds ratio [OR]
      1.75, 95% CI 1.37 to 2.24, p < 0.001), ostomy creation (OR 1.67, 95% CI 1.34 to
      2.08, p < 0.001), undergoing procedures without an anastomosis (OR 1.78, 95% CI
      1.42 to 2.24, p < 0.001), and open surgery (OR 2.09, 95% CI 1.72 to 2.53, p <
      0.001). Morbidly obese patients undergoing ES had more preoperative systemic
      inflammatory response syndrome/sepsis/septic shock than NL patients (72.8% vs
      57.7%, p = 0.004). CONCLUSIONS: Morbidly obese patients undergoing surgery for
      diverticulitis are nearly 10 years younger than NL patients and are more likely
      to require ES, ostomy creation, open surgery, and to undergo procedures without
      an anastomosis. Morbidly obese patients undergoing ES also have more preoperative
      systemic inflammatory response syndrome/sepsis/septic shock.

PMID- 24041559
TI  - Antibiotic prophylaxis for the prevention of surgical site infection after
      tension-free hernia repair: a Bayesian and frequentist meta-analysis.
AB  - BACKGROUND: Efficacy of antibiotic prophylaxis for the prevention of surgical
      site infection (SSI) after open tension-free hernia repair remains controversial.
      In light of additional data, the aim of this study was to determine whether
      antibiotic prophylaxis reduces SSI after hernia repair. STUDY DESIGN: We
      conducted a systematic review and meta-analysis to identify randomized controlled
      trials comparing antibiotic prophylaxis and the subsequent incidence of SSI after
      inguinal or femoral hernia repair. The primary outcomes measure was the incidence
      of SSI. Subgroup analysis was evaluated by stratifying the categories of SSI. The
      meta-analysis was performed using Bayesian and frequentist methods. RESULTS:
      Twelve studies were included in this meta-analysis; 1,902 patients received
      antibiotic prophylaxis and the other 1,936 patients were allocated to the control
      group. Incidence of SSI was 47 (pooled rate 3.0%) in the antibiotic group and 91
      (6.0%) in the control group. The number needed to treat to prevent 1 episode of
      SSI is 41. The Bayesian meta-analysis yielded a significant reduction of SSI in
      the antibiotic group (odds ratio = 0.49; 95% credible interval 0.25-0.81).
      Subgroup analysis showed that an antibiotic prophylaxis was beneficial for the
      prevention of superficial SSI (odds ratio = 0.40; 95% credible interval 0.12
      0.98), but not beneficial for prevention of deep SSI (odds ratio = 0.59; 95%
      credible interval 0.11-3.20). Also, the results were similar to those with
      frequentist methods. CONCLUSIONS: This meta-analysis suggests that antibiotic
      prophylaxis is efficacious for the prevention of SSI after open mesh hernia
      repair.

PMID- 24041560
TI  - Quality check of a quality measure: surgical wound classification discrepancies
      impact risk-stratified surgical site infection rates in pediatric appendicitis.
AB  - BACKGROUND: The impact of quality measures in health care and reimbursement is
      growing. Ensuring the accuracy of quality measures, including any risk
      stratification variables, is necessary. Surgical site infection rates, risk
      stratified by surgical wound classification (SWC) among other variables, are
      increasingly considered as quality measures. We hypothesized that hospital
      documented and diagnosis-based SWCs are frequently discordant and that diagnosis
      based SWCs better predict surgical site infection rates. STUDY DESIGN: All
      pediatric patients (ie, younger than 18 years old) at a single institution who
      underwent an appendectomy for appendicitis between October 1, 2010 and August 31,
      2011 were included. Each chart was reviewed to determine the hospital-documented
      SWC, which is recorded by the circulating nurse (options included clean, clean
      contaminated, contaminated, and dirty); SWC based on the surgeons' postoperative
      diagnosis, including contaminated (ie, acute nonperforated, nongangrenous
      appendicitis), dirty (ie, gangrenous and perforated appendicitis), and 30-day
      postoperative surgical site infections. RESULTS: Of the 312 evaluated
      appendicitis cases, the diagnosis-based and circulating nurse-based SWCs differed
      in 288 (92%) cases. The circulating nurse-based and diagnosis-based SWCs differed
      by more than one SWC in 176 (56%) cases. Surgical site infections were associated
      with worsening diagnosis-based SWC, but not with circulating nurse-based SWC.
      CONCLUSIONS: Significant discordance exists between hospital documentation by the
      circulating nurse- and surgeon diagnosis-based SWCs. Inconsistency in risk
      stratified quality measures can have a significant effect on outcomes measures,
      which can lead to misdirection of quality-improvement efforts, incorrect inter
      hospital rating, reduced reimbursements, and public misperceptions about quality
      of care.

PMID- 24041561
TI  - What surgical skills rural surgeons need to master.
AB  - BACKGROUND: As new technology is developed and scientific evidence demonstrates
      strategies to improve the quality of care, it is essential that surgeons keep
      current with their skills. Rural surgeons need efficient and targeted continuing
      medical education that matches their broader scope of practice. Developing such a
      program begins with an assessment of the learning needs of the rural surgeon. The
      aim of this study was to assess the learning needs considered most important to
      surgeons practicing in rural areas. STUDY DESIGN: A needs assessment
      questionnaire was administered to surgeons practicing in rural areas. An
      additional gap analysis questionnaire was administered to registrants of a skills
      course for rural surgeons. RESULTS: Seventy-one needs assessment questionnaires
      were completed. The self-reported procedures most commonly performed included
      laparoscopic cholecystectomy (n = 44), hernia repair (n = 42), endoscopy (n =
      43), breast surgery (n = 23), appendectomy (n = 20), and colon resection (n =
      18). Respondents indicated that they would most like to learn more skills related
      to laparoscopic colon resection (n = 16), laparoscopic antireflux procedures (n =
      6), laparoscopic common bile duct exploration/ERCP (n = 5), colonoscopy/advanced
      techniques and esophagogastroscopy (n = 4), and breast surgery (n = 4).
      Ultrasound, hand surgery, and leadership and communication were additional topics
      rated as useful by the respondents. Skills course participants indicated varying
      levels of experience and confidence with breast ultrasound, ultrasound for
      central line insertion, hand injury, and facial soft tissue injury. CONCLUSIONS:
      Our results demonstrated that surgeons practicing in rural areas have a strong
      interest in acquiring additional skills in a variety of general and subspecialty
      surgical procedures. The information obtained in this study may be used to guide
      curriculum development of further postgraduate skills courses targeted to rural
      surgeons.

PMID- 24041562
TI  - Identification of quality of care deficiencies in elderly surgical patients by
      measuring adherence to process-based quality indicators.
AB  - BACKGROUND: The ability to measure surgical quality of care is important and can
      lead to improvements in patient safety. As such, processes should be carried out
      in an identical fashion for all patients, regardless of how vulnerable or complex
      they are. Our objectives were to assess quality of surgical care delivered to
      elderly patients and to determine the association between patient characteristics
      and quality of care. STUDY DESIGN: This is a retrospective pilot cohort study,
      conducted in a single university-affiliated hospital. Using the institution's
      National Surgical Quality Improvement Program (NSQIP) database (2009 to 2010),
      143 consecutive patients 65 years or older, undergoing elective major abdominal
      surgery, were selected. Adherence to 15 process-based quality indicators (QIs)
      was measured, and a pass rate was calculated for each individual QI. The
      association between patient characteristics (age, sex, Charlson Comorbidity
      Index, functional status, wound class) and patient quality score was assessed
      using multiple linear regression. RESULTS: Quality indicators with the lowest
      pass rates included postoperative delirium screening (0%), level of care
      documentation (0.7%), cognition and functional assessment at discharge (4.9%),
      oral intake documentation (12.6%), and pressure ulcer risk assessment (35.0%).
      The mean patient quality score was 46.8% +/- 10.7% (range 16.7% to 75.0%). No
      association was found between patient characteristics and patient quality score.
      CONCLUSIONS: Quality of care delivered to elderly patients undergoing major
      surgery at our institution was generally poor and independent of patient
      characteristics. Although quality appears to be uniform across different
      patients, these results provide targets for quality improvement initiatives.

PMID- 24041563
TI  - What is the quality of reporting of studies of interventions to increase
      compliance with antibiotic prophylaxis?
AB  - BACKGROUND: Despite studies reporting successful interventions to increase
      antibiotic prophylaxis compliance, surgical site infections remain a significant
      problem. The reasons for this lack of improvement are unknown. This review
      evaluates the internal and external validity of quality improvement studies of
      interventions to increase surgical antibiotic prophylaxis compliance. STUDY
      DESIGN: Three investigators independently performed systematic literature
      searches and selected eligible studies that evaluated interventions to improve
      perioperative antibiotic prophylaxis timing, type, and/or discontinuation.
      Studies published before the Surgical Infection Prevention project inception in
      2002 were excluded. Each study was assessed based on modified criteria for
      evaluating quality improvement studies (Standards for Quality Improvement
      Reporting Excellence) and for facilitating implementation of evidence into
      practice (Reach-Efficacy-Adoption-Implementation-Maintenance). RESULTS: Forty-six
      articles met inclusion criteria; 93% reported improvement in antibiotic
      prophylaxis compliance. Surgical site infections were evaluated in 50% of studies
      and 65% reported an improvement. Less than 5% of studies used randomization,
      allocation concealment, or blinding. Nine percent of studies described efforts to
      minimize bias in the design results and analysis and 13% described a sample size
      calculation. Approximately one-third of studies described participant adoption of
      the intervention (26%), factors affecting generalizability (33%), or
      implementation barriers (37%). Most studies (80%) used multiple interventions; no
      single intervention was associated with change in compliance. Studies with the
      lowest baseline compliance showed the greatest improvement, regardless of the
      intervention(s). CONCLUSIONS: The methodology and reporting of quality
      improvement studies on perioperative antibiotic prophylaxis is suboptimal, and
      factors that would improve generalizability of successful intervention
      implementation are infrequently reported. Clinicians should use caution in
      applying the results of these studies to their general practice.

PMID- 24041564
TI  - Effects of nurse home visitation on cigarette smoking, pregnancy outcomes and
      breastfeeding: a randomized controlled trial.
AB  - OBJECTIVE: antenatal smoking is more prevalent among young women with low socio
      economic status. The aim of our study is to assess whether the VoorZorg
      programme, compared to usual care, is effective in reducing cigarette smoking
      among young high risk pregnant women. Furthermore, the effect of VoorZorg on
      pregnancy outcomes and on breast feeding will be described. DESIGN: a randomised
      controlled trial of VoorZorg, a nurse home visitation intervention, was
      undertaken over a 21/2 year period from 2007 to 2009. Data were collected between
      16 and 28 weeks gestation, 32 weeks gestation and at two months post partum on
      cigarette smoking status plus six months post partum for breastfeeding
      prevalence. Neonatal birth weight and gestation at birth were also collected.
      SETTING: participants living in 20 municipalities in the Netherlands.
      PARTICIPANTS: 460 pregnant women were recruited by different professionals.
      Inclusion criteria were age <26 years, <=28 weeks pregnancy with the first child,
      low educational level and some knowledge of the Dutch language. INTERVENTIONS:
      women in the intervention group received, in addition to usual care, the VoorZorg
      programme which consisted of 40-60 home visits by specialised nurses from
      pregnancy until two years after birth. FINDINGS: the percentage of smokers was
      significantly lower in the intervention group (40%) compared to the control group
      (48%) during pregnancy (p=0.03) and at two months post birth (49% and 62%;
      p=0.02). During pregnancy the number of daily cigarettes smoked was reduced in
      both groups. After birth, the intervention group smoked 50% less cigarettes
      compared to the control group (C: 8+/-10; I: 4+/-7 (mean+/-standard deviation
      (SD)), p=0.01). Furthermore, women in the intervention group did not smoke near
      the baby (C: 2+/-5; I: 0+/-0 (mean+/-SD) p=0.03). Birth weight and gestational
      age were similar in both groups (C: 3147g, 40 weeks; I: 3144g, 39 weeks (p=0.94,
      p=0.17)). Significantly more women in the intervention group were still breast
      feeding their baby at six months post -birth (C: 6%; I: 13%, p=0.04). KEY
      CONCLUSIONS: VoorZorg seemed to be effective in reducing cigarette smoking and in
      increasing breastfeeding duration. No effect was found on pregnancy outcomes.

PMID- 24041565
TI  - Prognostic significance of six-minute walk test in non-group 1 pulmonary
      hypertension.
AB  - OBJECTIVE: To assess the value of the six-minute walk test (6MWT) to predict
      outcome in non-group 1 pulmonary hypertension (PH). BACKGROUND: Distance walked
      during 6MWT has been widely used as a prognostic test in pulmonary arterial
      hypertension (group 1 pulmonary hypertension); however, little is known regarding
      its prognostic value in other groups of PH. METHODS: This was a retrospective
      study of 60 patients diagnosed of PH, Dana Point classification groups 2-5. 6MWT
      and echocardiography were performed in all cases. RESULTS: Forty patients (66.6%)
      were females. Mean age was 70.8 +/- 10.7 years (range: 32-85). Seven patients
      died after a mean follow-up of 23.2 +/- 16.7 months. Distance <400 m during 6MWT
      was associated with a higher risk for death (RR: 4.39; 95% CI: 1.13-17.05; p =
      0.03) and for clinical deterioration (death or need for hospitalization) (RR:
      2.76; 95% CI: 1.18-6.42; p = 0.02). CONCLUSIONS: 6MWT is useful to predict
      outcome in non-group 1 PH.

PMID- 24041566
TI  - Large embolus in transit - an unresolved therapeutic dilemma (case report and
      review of literature).
AB  - Floating right heart thrombus, also known as "emboli in transit" is a potentially
      fatal condition, of varying etiology and usually coexisting with massive
      pulmonary embolism. Although the mortality rate is as high as 40%, there are no
      established therapeutic guidelines. A case is presented of an 84 year old female
      with a history of colon cancer and coronary artery disease who presented with
      sudden onset unresponsiveness. She was intubated in the ED and started on
      intravenous pressor support. A free floating large right ventricular thrombus and
      dilated right ventricle were noted on transthoracic echocardiogram (TTE). She was
      managed medically with good short term outcome. Floating right heart thrombus is
      a rare occurrence. Recognition of signs and symptoms along with early TTE is
      critical for diagnosis and consideration of treatment modality. The existing
      literature does not offer a clear consensus for management of pulmonary embolism
      with co-existing mobile intra-cardiac thrombus. Choice of treatment is crucial
      and should be considered on a case-by-case basis after careful assessment of
      indications, contraindications, risks and benefits. 

PMID- 24041568
TI  - Operational aspects, pH transition and microbial shifts of a H2S desulfurizing
      biotrickling filter with random packing material.
AB  - Pall rings, a common random packing material, were used in the biotrickling
      filtration of biogas with high H2S. Assessment of 600d of operation covered the
      reactor start-up, the operation at neutral pH and the transition from neutral to
      acid pH. During the start-up period, operational parameters such as the aeration
      rate and the trickling liquid velocity were optimized. During the steady-state
      operation at neutral pH, the performance of the random packing material was
      investigated by reducing the gas contact time at both constant and increasing H2S
      loads. The random packing material showed similar elimination capacities and
      removal efficiencies in comparison with previous studies with a structured
      packing material, indicating that Pall rings are suitable for biogas
      desulfurization in biotrickling filters. The diversity of Eubacteria and the
      structure of the community were investigated before and after the pH transition
      using the bacterial tag-encoded FLX amplicon pyrosequencing. The pH transition to
      acid pH drastically reduced the microbial diversity and produced a progressive
      specialization of the sulfur-oxidizing bacteria community without any detrimental
      effect on the overall desulfurizing capacity of the reactor. During acidic pH
      operation, a persistent accumulation of elemental sulfur was found. 

PMID- 24041569
TI  - Factors affecting catalysis of copper corrosion products in NDMA formation from
      DMA in simulated premise plumbing.
AB  - This study investigated the effects of corrosion products of copper, a metal
      commonly employed in household plumbing systems, on N-nitrosodimethylamine (NDMA)
      formation from a known NDMA precursor, dimethylamine (DMA). Copper-catalyzed NDMA
      formation increased with increasing copper concentrations, DMA concentrations,
      alkalinity and hardness, but decreased with increasing natural organic matter
      (NOM) concentration. pH influenced the speciation of chloramine and the
      interactions of copper with DMA. The transformation of monochloramine (NH2Cl) to
      dichloramine and complexation of copper with DMA were involved in elevating the
      formation of NDMA by copper at pH 7.0. The inhibiting effect of NOM on copper
      catalysis was attributed to the rapid consumption of NH2Cl by NOM and/or the
      competitive complexation of NOM with copper to limit the formation of DMA-copper
      complexes. Hardness ions, as represented by Ca(2+), also competed with copper for
      binding sites on NOM, thereby weakening the inhibitory effect of NOM on NDMA
      formation. Common copper corrosion products also participated in these reactions
      but in different ways. Aqueous copper released from malachite [Cu2CO3(OH)2] was
      shown to promote NDMA formation while NDMA formation decreased in the presence of
      CuO, most likely due to the adsorption of DMA. 

PMID- 24041567
TI  - Predictors of urinary bisphenol A and phthalate metabolite concentrations in
      Mexican children.
AB  - Exposure to endocrine disrupting chemicals such as bisphenol A (BPA) and
      phthalates is prevalent among children and adolescents, but little is known
      regarding important sources of exposure at these sensitive life stages. In this
      study, we measured urinary concentrations of BPA and nine phthalate metabolites
      in 108 Mexican children aged 8-13 years. Associations of age, time of day, and
      questionnaire items on external environment, water use, and food container use
      with specific gravity-corrected urinary concentrations were assessed, as were
      questionnaire items concerning the use of 17 personal care products in the past
      48-h. As a secondary aim, third trimester urinary concentrations were measured in
      99 mothers of these children, and the relationship between specific gravity
      corrected urinary concentrations at these two time points was explored. After
      adjusting for potential confounding by other personal care product use in the
      past 48-h, there were statistically significant (p<0.05) positive associations in
      boys for cologne/perfume use and monoethyl phthalate (MEP), mono(3-carboxypropyl)
      phthalate (MCPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2
      ethyl-5-oxohexyl) phthalate (MEOHP), and in girls for colored cosmetics use and
      mono-n-butyl phthalate (MBP), mono(2-ethylhexyl) phthalate (MEHP), MEHHP, MEOHP,
      and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), conditioner use and MEP,
      deodorant use and MEP, and other hair products use and MBP. There was a
      statistically significant positive trend for the number of personal care products
      used in the past 48-h and log-MEP in girls. However, there were no statistically
      significant associations between the analytes and the other questionnaire items
      and there were no strong correlations between the analytes measured during the
      third trimester and at 8-13 years of age. We demonstrated that personal care
      product use is associated with exposure to multiple phthalates in children. Due
      to rapid development, children may be susceptible to impacts from exposure to
      endocrine disrupting chemicals; thus, reduced or delayed use of certain personal
      care products among children may be warranted.

PMID- 24041570
TI  - Coordinated transcriptional regulation of Hspa1a gene by multiple transcription
      factors: crucial roles for HSF-1, NF-Y, NF-kappaB, and CREB.
AB  - Although the transcript level of inducible heat shock protein 70.3 (Hsp70.3, also
      known as Hspa1a) is altered in various disease states, its transcriptional
      regulation remains incompletely understood. Here, we systematically analyzed the
      Hspa1a promoter to identify major cis elements and transcription factors that may
      govern the constitutive/inducible gene expression. Computational analyses coupled
      with extensive in vitro (promoter-reporter activity and electrophoretic mobility
      shift assays) and in vivo (chromatin immunoprecipitation assays) revealed
      interaction of several transcription factors with Hspa1a promoter motifs: HSF-1
      (heat shock factor 1) at -114/-97 bp and -788/-777bp, NF-Y (nuclear transcription
      factor Y) at -73/-58 bp, NF-kappaB (nuclear factor kappa B) at -133/-124 bp, and
      CREB (cAMP response element binding protein) at -483/-476 bp. Consistently, siRNA
      (small interfering RNA)-mediated down-regulation of each of these transcription
      factors caused substantial reduction of endogenous Hspa1a expression. Heat-shock
      induced activation of Hspa1a was coordinately regulated by HSF-1 and NF-Y/NF
      kappaB. The Hspa1a expression was augmented by TNF-alpha (tumor necrosis factor
      alpha) and forskolin in NF-kappaB and CREB-dependent manners, respectively. NF
      kappaB and CREB also activated Hspa1a transcription in cardiac myoblasts upon
      exposure to ischemia-like conditions. Taken together, this study discovered
      previously unknown roles for NF-kappaB and CREB to regulate Hspa1a expression and
      a coordinated action by several transcription factors for Hspa1a transactivation
      under heat-shock/ischemia-like conditions and thereby provided new insights into
      the mechanism of Hspa1a regulation.

PMID- 24041572
TI  - Evolved Escherichia coli strains for amplified, functional expression of membrane
      proteins.
AB  - The major barrier to the physical characterization and structure determination of
      membrane proteins is low protein yield and/or low functionality in recombinant
      expression. The enteric bacterium Escherichia coli is the most widely employed
      organism for producing recombinant proteins. Beside several advantages of this
      expression host, one major drawback is that the protein of interest does not
      always adopt its native conformation and may end up in large insoluble
      aggregates. We describe a robust strategy to increase the likelihood of
      overexpressing membrane proteins in a functional state. The method involves
      fusion in tandem of green fluorescent protein and the erythromycin resistance
      protein (23S ribosomal RNA adenine N-6 methyltransferase, ErmC) to the C-terminus
      of a target membrane protein. The fluorescence of green fluorescent protein is
      used to report the folding state of the target protein, whereas ErmC is used to
      select for increased expression. By gradually increasing the erythromycin
      concentration of the medium and testing different membrane protein targets, we
      obtained a number of evolved strains of which four (NG2, NG3, NG5 and NG6) were
      characterized and their genome was fully sequenced. Strikingly, each of the
      strains carried a mutation in the hns gene, whose product is involved in genome
      organization and transcriptional silencing. The degree of expression of
      (membrane) proteins correlates with the severity of the hns mutation, but cells
      in which hns was deleted showed an intermediate expression performance. We
      propose that (partial) removal of the transcriptional silencing mechanism changes
      the levels of proteins essential for the functional overexpression of membrane
      proteins. 

PMID- 24041571
TI  - Thermodynamic and structural basis for relaxation of specificity in protein-DNA
      recognition.
AB  - As a novel approach to the structural and functional properties that give rise to
      extremely stringent sequence specificity in protein-DNA interactions, we have
      exploited "promiscuous" mutants of EcoRI endonuclease to study the detailed
      mechanism by which changes in a protein can relax specificity. The A138T
      promiscuous mutant protein binds more tightly to the cognate GAATTC site than
      does wild-type EcoRI yet displays relaxed specificity deriving from tighter
      binding and faster cleavage at EcoRI* sites (one incorrect base pair). AAATTC
      EcoRI* sites are cleaved by A138T up to 170-fold faster than by wild-type enzyme
      if the site is abutted by a 5'-purine-pyrimidine (5'-RY) motif. When wild-type
      protein binds to an EcoRI* site, it forms structurally adapted complexes with
      thermodynamic parameters of binding that differ markedly from those of specific
      complexes. By contrast, we show that A138T complexes with 5'-RY-flanked AAATTC
      sites are virtually indistinguishable from wild-type-specific complexes with
      respect to the heat capacity change upon binding (?C degrees P), the change in
      excluded macromolecular volume upon association, and contacts to the phosphate
      backbone. While the preference for the 5'-RY motif implicates contacts to
      flanking bases as important for relaxed specificity, local effects are not
      sufficient to explain the large differences in ?C degrees P and excluded volume,
      as these parameters report on global features of the complex. Our findings
      therefore support the view that specificity does not derive from the additive
      effects of individual interactions but rather from a set of cooperative events
      that are uniquely associated with specific recognition. 

PMID- 24041573
TI  - Preparation and characterization of DNA/allophane composite hydrogels.
AB  - The preparation and characterization of the composite hydrogels based on double
      stranded deoxyribonucleic acid (DNA) and natural allophane (AK70) were reported.
      To understand the propensity of the natural allophane to adsorb the DNA
      molecules, using zeta potential measurement, Fourier transform infrared
      spectroscopy (FTIR) and electrophoresis analyses assessed the adsorption
      characteristics. The freeze-dried DNA/AK70 hydrogels were demonstrated that the
      DNA bundle structure with a width of ~2MUm and a length of ~15-20MUm was wrapped
      around the clustered allophane particles as revealed by FE-SEM/EDX analysis. The
      incorporation of AK70 in hydrogels induced the increase in the enthalpy of the
      helix-coil transition of DNA duplex due to the restricted molecular motions of
      the DNA duplex facilitated by the interaction between the phosphate groups of DNA
      and the protonated (+)(OH2)Al(OH2) groups on the wall perforations of the
      allophane. 

PMID- 24041574
TI  - Plasma microRNA signature as a noninvasive biomarker for acute graft-versus-host
      disease.
AB  - Acute graft-versus-host disease (aGVHD) is the leading cause of morbidity and
      mortality after allogeneic hematopoietic cell transplantation (HCT).
      Approximately 35% to 50% of HCT recipients develop aGVHD; however, there are no
      validated diagnostic and predictive blood biomarkers for aGVHD in clinical use.
      Here, we show that plasma samples from aGVHD patients have a distinct microRNA
      (miRNA) expression profile. We found that 6 miRNAs (miR-423, miR-199a-3p, miR
      93*, miR-377, miR-155, and miR-30a) were significantly upregulated in the plasma
      of aGVHD patients (n = 116) when compared with non-GVHD patients (n = 52) in
      training and validation phases. We have developed a model including 4 miRNAs (miR
      423, miR-199a-3p, miR-93*, and miR-377) that can predict the probability of aGVHD
      with an area under the curve of 0.80. Moreover, these elevated miRNAs were
      detected before the onset of aGVHD (median = 16 days before diagnosis). In
      addition, the levels of these miRNAs were positively associated with aGVHD
      severity, and high expression of the miRNA panel was associated with poor overall
      survival. Furthermore, the miRNA signature for aGVHD was not detected in the
      plasma of lung transplant or nontransplant sepsis patients. Our results have
      identified a specific plasma miRNA signature that may serve as an independent
      biomarker for the prediction, diagnosis, and prognosis of aGVHD. 

PMID- 24041576
TI  - Genome sequencing of lymphoid malignancies.
AB  - Our understanding of the pathogenesis of lymphoid malignancies has been
      transformed by next-generation sequencing. The studies in this review have used
      whole-genome, exome, and transcriptome sequencing to identify recurring
      structural genetic alterations and sequence mutations that target key cellular
      pathways in acute lymphoblastic leukemia (ALL) and the lymphomas. Although each
      tumor type is characterized by a unique genomic landscape, several cellular
      pathways are mutated in multiple tumor types-transcriptional regulation of
      differentiation, antigen receptor signaling, tyrosine kinase and Ras signaling,
      and epigenetic modifications-and individual genes are mutated in multiple tumors,
      notably TCF3, NOTCH1, MYD88, and BRAF. In addition to providing fundamental
      insights into tumorigenesis, these studies have also identified potential new
      markers for diagnosis, risk stratification, and therapeutic intervention. Several
      genetic alterations are intuitively "druggable" with existing agents, for
      example, kinase-activating lesions in high-risk B-cell ALL, NOTCH1 in both
      leukemia and lymphoma, and BRAF in hairy cell leukemia. Future sequencing efforts
      are required to comprehensively define the genetic basis of all lymphoid
      malignancies, examine the relative roles of germline and somatic variation,
      dissect the genetic basis of clonal heterogeneity, and chart a course for
      clinical sequencing and translation to improved therapeutic outcomes. 

PMID- 24041575
TI  - Nfix is a novel regulator of murine hematopoietic stem and progenitor cell
      survival.
AB  - Hematopoietic stem cells are both necessary and sufficient to sustain the
      complete blood system of vertebrates. Here we show that Nfix, a member of the
      nuclear factor I (Nfi) family of transcription factors, is highly expressed by
      hematopoietic stem and progenitor cells (HSPCs) of murine adult bone marrow.
      Although short hairpin RNA-mediated knockdown of Nfix expression in Lineage(-)Sca
      1(+)c-Kit(+) HSPCs had no effect on in vitro cell growth or viability, Nfix
      depleted HSPCs displayed a significant loss of colony-forming potential, as well
      as short- and long-term in vivo hematopoietic repopulating activity. Analysis of
      recipient mice at 4 to 20 days posttransplant revealed that Nfix-depleted HSPCs
      are established in the bone marrow, but fail to persist due to increased
      apoptotic cell death. Gene expression profiling of Nfix-depleted HSPCs reveals
      that loss of Nfix expression in HSPCs is concomitant with a decrease in the
      expression of multiple genes known to be important for HSPCs survival, such as
      Erg, Mecom, and Mpl. These data reveal that Nfix is a novel regulator of HSPCs
      survival posttransplantation and establish a role for Nfi genes in the regulation
      of this cellular compartment. 

PMID- 24041577
TI  - Autocrine TNF-alpha production supports CML stem and progenitor cell survival and
      enhances their proliferation.
AB  - Chronic myeloid leukemia (CML) stem cells are not dependent on BCR-ABL kinase for
      their survival, suggesting that kinase-independent mechanisms must contribute to
      their persistence. We observed that CML stem/progenitor cells (SPCs) produce
      tumor necrosis factor-alpha (TNF-alpha) in a kinase-independent fashion and at
      higher levels relative to their normal counterparts. We therefore investigated
      the role of TNF-alpha and found that it supports survival of CML SPCs by
      promoting nuclear factor kappaB/p65 pathway activity and expression of the
      interleukin 3 and granulocyte/macrophage-colony stimulating factor common beta
      chain receptor. Furthermore, we demonstrate that in CML SPCs, inhibition of
      autocrine TNF-alpha signaling via a small-molecule TNF-alpha inhibitor induces
      apoptosis. Moreover TNF-alpha inhibition combined with nilotinib induces
      significantly more apoptosis relative to either treatment alone and a reduction
      in the absolute number of primitive quiescent CML stem cells. These results
      highlight a novel survival mechanism of CML SPCs and suggest a new putative
      therapeutic target for their eradication. 

PMID- 24041578
TI  - Runx1-deficient afferents impair visceral nociception, exacerbating dextran
      sodium sulfate-induced colitis.
AB  - Colitis is a group of inflammatory and auto-immune disorders that affect the
      tissue lining of the gastrointestinal (GI) system. Studies of chemically-induced
      animal models of colitis have indicated that nociceptive afferents or
      neuropeptides have differing effects on GI inflammation. However, the molecular
      mechanisms involved in visceral pain and the role of visceral sensory afferents
      involved in the modulation of colitis remains unclear. A previous study
      demonstrated that Runx1, a Runt domain transcription factor, is restricted to
      nociceptors. In these neurons, Runx1 regulates the expression of numerous ion
      channels and receptors, controlling the lamina-specific innervation patterns of
      nociceptive afferents in the spinal cord. Moreover, mice that lack Runx1 exhibit
      specific defects in thermal and neuropathic pain. To examine the function of
      Runx1 in visceral nociception, we employed double-transgenic mice (WntCre:
      Runx1(F/F)), in which the expression of Runx1 was specifically disrupted in the
      sensory neurons. To determine the role of Runx1 in visceral pain sensation, the
      WntCre: Runx1(F/F) mice and their control littermates (Runx1(F/F)) were treated
      using dextran sodium sulfate (DSS) to induce colitis. The results indicated that
      disrupted Runx1 in the sensory afferents resulted in: (1) impairment of the
      visceral pain sensation in murine DSS-induced colitis; (2) exacerbating the
      phenotypes in murine DSS-induced colitis; (3) a differential effect on the
      production of pro- and anti-inflammatory cytokines in the colon tissues isolated
      from mice treated using DSS and 2,4,6-trinitrobenzene sulfonic acid (TNBS)
      induced colitis; and (4) alteration of the distribution of lymphocytes and mast
      cells in mucosa. These results show that the function of Runx1 in sensory
      afferents is vital for modulating visceral pain and the neuro-immune axis.

PMID- 24041579
TI  - The acceleration dependent validity and reliability of 10 Hz GPS.
AB  - OBJECTIVES: To examine the validity and inter-unit reliability of 10 Hz GPS for
      measuring instantaneous velocity during maximal accelerations. DESIGN:
      Experimental. METHODS: Two 10 Hz GPS devices secured to a sliding platform
      mounted on a custom built monorail were towed whilst sprinting maximally over 10
      m. Displacement of GPS devices was measured using a laser sampling at 2000 Hz,
      from which velocity and mean acceleration were derived. Velocity data was pooled
      into acceleration thresholds according to mean acceleration. Agreement between
      laser and GPS measures of instantaneous velocity within each acceleration
      threshold was examined using least squares linear regression and Bland-Altman
      limits of agreement (LOA). Inter-unit reliability was expressed as typical error
      (TE) and a Pearson correlation coefficient. RESULTS: Mean bias +/- 95% LOA during
      accelerations of 0-0.99 ms(-2) was 0.12 +/- 0.27 ms(-1), decreasing to -0.40 +/-
      0.67 ms(-1) during accelerations >4 ms(-2). Standard error of the estimate +/-
      95% CI (SEE) increased from 0.12 +/- 0.02 ms(-1) during accelerations of 0-0.99
      ms(-2) to 0.32 +/- 0.06 ms(-1) during accelerations >4 ms(-2). TE increased from
      0.05 +/- 0.01 to 0.12 +/- 0.01 ms(-1) during accelerations of 0-0.99 ms(-2) and
      >4 ms(-2) respectively. CONCLUSION: The validity and reliability of 10 Hz GPS for
      the measurement of instantaneous velocity has been shown to be inversely related
      to acceleration. Those using 10 Hz GPS should be aware that during accelerations
      of over 4 ms(-2), accuracy is compromised.

PMID- 24041580
TI  - Comparison of the primary stability of different tibial baseplate concepts to
      retain both cruciate ligaments during total knee arthroplasty.
AB  - BACKGROUND: A novel tibial baseplate design (Transversal Support Tibial Plateau)
      as a new treatment concept for bi-cruciate retaining total knee arthroplasty is
      evaluated for mechanical stability and compared to other tibial baseplate
      designs. This concept should provide better primary stability and thus, less
      subsidence, than implantation of two separate unicondylar tibial baseplates.
      METHODS: Different baseplates were implanted into synthetic bone specimens
      (Sawbones(r) Pacific Research Laboratories, Inc., Washington, USA), all
      uncemented. Using a standardized experimental setup, subsidence was achieved,
      enabling comparison of the models regarding primary stability. FINDINGS: Overall
      implant subsidence was significantly increased for the two separate unicondylar
      tibial baseplates versus the new Transversal Support Tibial Plateau concept,
      which showed comparable levels to a conventional tibial baseplate. Reduced
      subsidence results in better primary stability. INTERPRETATION: Linking of two
      separate baseplates appears to provide increased primary stability in terms of
      bony fixation, comparable to that of a conventional single tibial baseplate.

PMID- 24041581
TI  - Biliary Pancreatitis. Liver Function Tests and Common Biliopancreatic Channel
      Kinetics--Biliopancreatic Reflux.
AB  - OBJECTIVE: To determine the prevalence of biliopancreatic reflux (BPR) in
      patients with biliary pancreatitis (BP) undergoing elective cholecystectomy with
      intraoperative cholangiography (IOC) in comparison with a control group of
      symptomatic cholelithiasis (CG). PATIENTS AND METHODS: Retrospective review of
      107 consecutive BP cases. BPR was determined by IOC and liver function tests
      (LFT) were recorded at admission (A), 48hours, and preoperative examination (P).
      LFT analysis between A and P were analysed between groups with respect to BPR,
      time interval to cholecystectomy within the same group and by determination of
      observed value/maximum normal value ratio (OV/MNV). RESULTS: BPR incidence was
      38.3% in BP in comparison with 5% in CG (p=0.0001) it was independent from
      interval time to cholecystectomy, in contrast with Odditis, suggesting an
      anatomical condition for CCBP and a functional one for Odditis. LFT analysis
      showed no differences in relation to BPR incidence. LFT excluding AP and GGT
      returned to normal values with significant differences in OV/MNV when BPR was
      present which points to an increased cholestasis in BPR group. US dilatation of
      CBD was noted in 10.3% and was associated to CCBP. CONCLUSIONS: BPR in BP
      increases cholestasis and contributes to confusion in the estimation of common
      bile duct stones increasing ERCP-EE rates. US and biochemical markers of CBDS
      show a low specificity due to BPR-CCBP which suggests that MRI-cholangiography is
      a mandatory exploration before ERCP-EE examination.

PMID- 24041582
TI  - Ultrastructure of epididymal epithelium and its interaction with the sperm in the
      soft-shelled turtle Pelodiscus sinensis.
AB  - The epididymis of the soft-shelled turtle Pelodiscus sinensis was examined under
      light and transmission electron microscopes to determine the morphological
      characteristics, as well as their changes at different phases of the seasonal
      reproductive cycle. Three distinct regions, viz., cranial, middle and caudal were
      identified in the epididymis based on anatomical characteristics. The epididymal
      epithelium consists of five different cell types: principal, narrow, apical,
      clear and basal cells. Principal cells, which are the most abundant, together
      with basal cells are present along the entire length. Ultrastructural evidence
      suggests that all of the principal cells in each of the regions function in both
      absorption and secretion. Narrow cells and apical cells are rare and only
      confined to the cranial region. The clear cells, for the first time reported in
      the turtle epididymis, are confined to middle and caudal regions; these cells
      showed strong PAS-positive granulation in apical position, and secretory activity
      by a holocrine process, especially in the middle region. There was a significant
      difference in the epithelium height of all the regions between the reproductive
      season and the non-reproductive season. Sperm are stored in the epididymis
      throughout the year. Apart from the mature spermatozoa, immature spermatozoa with
      normal morphology are also observed. Under TEM, the immature spermatozoa showed a
      large amount of cytoplasm located eccentrically on the midpiece wrapped by plasma
      membrane, with some cytoplasm extended to the posterior of the head. Furthermore,
      the interactions of sperm with the epididymal epithelium were observed. Some
      sperm are associated with the secretory material in the lumen; other sperm are
      inserted into the intercellular space between the epithelial cells. 

PMID- 24041583
TI  - Atom probe study of vanadium interphase precipitates and randomly distributed
      vanadium precipitates in ferrite.
AB  - Atom probe tomography and transmission electron microscopy were used to examine
      the precipitation reaction in the austenite and ferrite phases in vanadium micro
      alloyed steel after a thermo-mechanical process. It was observed that only in the
      ferrite phase precipitates could be found, whereupon two different types were
      detected. Thus, the aim was to reveal the difference between these two types. The
      first type was randomly distributed precipitates from V supersaturated ferrite
      and the second type V interphase precipitates. Not only the arrangement of the
      particles was different also the chemical composition. The randomly distributed
      precipitates consisted of V, C and N in contrast to that the interphase
      precipitates showed a composition of V, C and Mn. Furthermore the randomly
      distributed precipitates had maximum size of 20 nm and the interphase
      precipitates a maximum size of 15 nm. It was assumed that the reason for these
      differences is caused by the site in which they were formed. The randomly
      distributed precipitates were formed in a matrix consisting mainly of 0.05 at% C,
      0.68 at% Si, 0.03 at% N, 0.145 at% V and 1.51 at% Mn. The interphase precipitates
      were formed in a region with a much higher C, Mn and V content.

PMID- 24041584
TI  - Non-centro-symmetric electron diffraction pattern of icosahedral quasicrystal
      induced by combination of linear phason strain and curvature of Ewald sphere.
AB  - Non-centro-symmetric characteristics are observed in the experimental electron
      diffraction patterns (EDPs) from the icosahedral quasicrystalline precipitates in
      ZrAlNiCuNb alloys. Different from the well-known breaking of the Friedel's law,
      where a strong dynamical effect will reveal in EDPs the concealed non-centro
      symmetry originated from the crystal structures themselves, the current results
      can be interpreted in terms of changes in deviation parameters due to a delicate
      combination of the linear phason strain characteristic of quasicrystals and the
      curvature of Ewald sphere. After taking this effect into consideration, the
      corresponding simulated EDPs fit quite well to the experimental data. 

PMID- 24041585
TI  - The effect of walking with poles on the distribution of plantar pressures in
      normal subjects.
AB  - BACKGROUND: Elevated pressures on the plantar surface of the foot increases the
      potential of developing foot ulcers in patients who are at risk. Walking with
      poles has been shown to reduce ground reaction and joint forces; however, the
      effect on plantar pressures is unknown. OBJECTIVE: To determine the effectiveness
      of walking with poles on reducing plantar pressure on the foot after brief
      instructions and 1 week of self-guided practice. It was hypothesized that there
      would be a significant reduction in pressure in the foot when walking with poles.
      DESIGN: This was a nonblinded, randomized, crossover study. SETTING: This study
      took place in a motion analysis laboratory located at an academic institution.
      METHODS: Thirty-five healthy subjects were instructed on 2 gait patterns when
      using walking poles. When walking with the 2-point pattern, the subjects placed
      the poles of the opposite side with the foot in stance. The 3-point pattern
      required the subjects to place both poles with the right foot. After 1 week of
      unsupervised practice, plantar pressures under the metatarsal heads and hallux of
      the right foot were measured by using a pedobarograph mat while walking with and
      without the poles. MAIN OUTCOME MEASUREMENTS: Mean plantar pressures and impulses
      were recorded from 5 trials for each walking condition: no poles, 2-point, and 3
      point styles. RESULTS: Walking with the poles resulted in significant reductions
      (P <= .01) in mean and impulse of pressure under the metatarsal heads region of
      up to 24%; no significant changes were seen under the heel or hallux. The 3-point
      style resulted in a significantly greater reduction of pressure compared with the
      2-point style (P = .002) in the metatarsal region but not the hallux.
      CONCLUSIONS: Walking with poles was easy to learn and may be a useful part of the
      management of persons at risk for developing plantar foot ulcers.

PMID- 24041586
TI  - Co-contractive activation of the superficial multifidus during volitional
      preemptive abdominal contraction.
AB  - OBJECTIVE: To investigate whether the superficial multifidus (MF) muscle at the
      lower lumbar spine displayed co-contraction during volitional preemptive
      abdominal contraction (VPAC) through the abdominal drawing-in maneuver (ADIM) or
      the abdominal bracing maneuver (ABM) in 3 different postural positions. DESIGN: A
      within-subject cohort design. SETTING: A clinical laboratory. PARTICIPANTS: A
      healthy convenience sample of 21 women and 13 men; mean age (SD), 25.5 +/- 6.5
      years. METHODS: We collected surface electromyographic measurements for the
      superficial MF at the L5 vertebral level and abdominal wall muscles. Ultrasound
      imaging was used during screening and testing sessions for confirming transverse
      abdominis muscle activation while subjects maintained a relaxed state without
      volitional abdominal contraction (no-VPAC) and performed ADIM and ABM in 3
      postural positions: supine, 4-point kneeling, and upright standing. MAIN OUTCOME
      MEASUREMENT: The frequency of superficial MF co-contraction occurrences
      (percentage of the total number of conditions) was measured during ADIM and ABM
      in 3 different postural positions. DATA ANALYSES: A Cochran Q test for k-related
      samples (alpha = 0.05) was used for data analysis. RESULTS: Activation of the
      abdominal wall by using either VPAC strategy resulted in a significantly greater
      MF co-contraction occurrence when compared with no-VPAC in each position. The ABM
      produced a significantly higher MF co-contractive occurrence versus the ADIM in
      the supine position. CONCLUSION: Both VPAC strategies produced a co-contractive
      MF response, which appears to be important for lumbar segmental stabilization and
      control. Analysis of the results suggests that VPAC strategies are appropriate
      for coactivating the MF, which can enhance spinal protection and rehabilitation
      responses.

PMID- 24041587
TI  - Intra-rater reliability of ultrasound imaging of wrist extensor muscles in
      patients with tetraplegia.
AB  - OBJECTIVES: (i) To determine the intra-rater reliability and precision of the
      ultrasound cross-sectional area (CSA) measurements of the wrist extensors in
      individuals with spinal cord injury (SCI), and (ii) to determine whether
      tetraplegia has a negative influence on the reliability and precision for these
      measurements. DESIGN: A repeated-measures cross-sectional study. SETTINGS:
      Clinical hospital and academic settings. METHODS: The study was conducted with 20
      men with SCI (9 paraplegia and 11 tetraplegia) and 10 able-bodied controls.
      Ultrasound images were captured of the right side extensor carpi radialis-longus
      (ECRL) and the extensor digitorum communis (EDC) were captured in 2 sessions
      separated by 48-72 hours. RESULTS: The intraclass correlation coefficients for
      the CSA measurements of the ECRL and EDC muscles were greater than 0.87 for all 3
      groups. The standard error of the measure (SEM) ranged from 0.11-0.22 cm(2) for
      the ECRL and 0.13-0.27 cm(2) for the EDC. The minimal detectable change of ECL
      ranged from 0.16 to 0.31 cm(2) and of EDC from 0.19 to 0.38 cm(2). The group
      differences in muscle CSA of both muscles were found; these differences were
      greater than the calculated minimal detectable changes. The intraclass
      correlation coefficients were lower and the SEMs and minimal detectable changes
      were higher for the group with tetraplegia compared with the able-bodied controls
      and the group with paraplegia. CONCLUSIONS: This study documented substantial
      intra-rater reliability of measurements of the ECRL and ECD CSA by using
      ultrasound images, which support the use of this technique to effectively
      evaluate the musculoskeletal changes after SCI and during rehabilitation.
      Skeletal muscle atrophy in persons with tetraplegia might have a negative
      influence on the reliability and precision of these CSA measurements; however,
      these differences in reliability and precision are not of clinical significance.

PMID- 24041588
TI  - Adenosine-uridine-rich element is one of the required cis-elements for
      epimastigote form stage-specific gene expression of the congolense epimastigote
      specific protein.
AB  - It is known that gene expression in kinetoplastida is regulated post
      transcriptionally. Several previous studies have shown that stage-specific gene
      expression in trypanosomes is regulated by cis-elements located in the 3'
      untranslated region (UTR) of each mRNA and also by RNA binding proteins. Our
      previous study revealed that gene expression of congolense epimastigote specific
      protein (cesp) was regulated by cis-elements located in the 3'UTR. In the present
      study, we identified the adenosine and uridine rich region in the cesp 3'UTR.
      Using transgenic trypanosome cell lines with different egfp expression cassettes,
      we showed that this adenosine and uridine rich region is one of the regulatory
      elements for epimastigote form (EMF) stage-specific gene expression via the
      regulatory cis-element of the eukaryotic AU rich element (ARE). Therefore this
      required element within the cesp 3'UTR was designated as T. congolense ARE. This
      required cis-element might selectively stabilize mRNA in the EMF stage and
      destabilize mRNA in other stages. By RNA electro mobility shift assay, unknown
      stage-specific RNA binding proteins (RBPs) whose sequences specifically
      interacted with the required cis-element were found. These results indicate that
      EMF stage specific cis-element and RBP complexes might specifically stabilize
      cesp mRNA in EMF. 

PMID- 24041589
TI  - Increase of gluthatione S-transferase, carboxyl esterase and carbonyl reductase
      in Fasciola hepatica recovered from triclabendazole treated sheep.
AB  - Fasciolasis is a zoonotic parasitic disease caused by Fasciola hepatica and its
      control is mainly based on the use of triclabendazole (TCBZ). Parasite resistance
      to different anthelmintics is growing worldwide, including the resistance of F.
      hepatica to TCBZ. In the present work we evaluate "in vivo" the activity of
      xenobiotic metabolizing enzymes of phase I (carboxyl esterases) and phase II
      (glutathione S-transferases and carbonyl reductases) recovered of flukes from
      sheep treated with TCBZ. All three enzymes showed increased activity in TCBZ
      flukes returning 60h post-treatment at similar to baseline unexposed flukes. TCBZ
      action may induce secondary oxidative stress, which may explain the observed
      increment in activities of the analyzed enzymes as a defensive mechanism. The
      enzymes analyzed are candidates to participate actively in the development of
      resistance at TCBZ in F. hepatica. 

PMID- 24041590
TI  - Effects of nutritional status and dietetic interventions on survival in Cystic
      Fibrosis patients before and after lung transplantation.
AB  - BACKGROUND: This study retrospectively investigated nutritional status, dietetic
      intervention and intake in Cystic Fibrosis (CF) patients before and after lung
      transplantation (LTX). METHODS: Body Mass Index (BMI), Fat Free Mass Index (FFMI)
      and nutritional intake were retrieved from 75 out-patients aged 15-53 years.
      Patients were seen every 3-4 months during the waiting list time (range 0-81
      months) and up to 116 months after LTX. Survival was measured in months. RESULTS:
      The median BMI at baseline was 19.2 kg/m(2) (range: 15.3 to 28.4 kg/m(2)) with 29
      patients (39%) below <=18.5 kg/m(2). FFMI (measured in 65 patients) had a median
      of 15.2 kg/m(2) (range: 11.1 to 22.4 kg/m(2)) with 39 patients (60%) <=16.7
      kg/m(2) (men) or <=14.6 kg/m(2) (women). Median energy intake was 2800 kcal, 239
      kcal higher than the estimated energy requirement. However, 8 patients consumed
      >=500 kcal less than recommended. Protein intake was 104 (range 60-187) g or 1.9
      g/kg per day. Despite dietetic intervention with oral nutritional supplements
      (ONS) (36 patients), tube feeding (12 patients), or both (13 patients), BMI and
      FFMI hardly improved pre-LTX. LTX was performed in 51 patients (68%); 10 patients
      died during follow-up, median survival time was 41 months. A BMI <=18.5 kg/m(2)
      was more prevalent in patients who died before LTX (6/9) or who died after LTX
      (4/10) than in patients who were still alive on the waiting list (5/15) or who
      survived LTX (14/41). Results for FFMI were comparable. From 6-12 months post
      LTX, BMI and FFMI markedly improved, especially in underweight patients.
      CONCLUSION: A BMI <=18.5 kg/m(2) and an FFMI <=16.7 kg/m(2) (men) or <=14.6
      kg/m(2) (women) appears to impair survival in LTX candidates with CF. Patients
      maintained a low body weight before LTX. After LTX weight gain is achieved.

PMID- 24041591
TI  - Quantification and efficiency of Lactobacillus sakei strain mixtures used as
      protective cultures in ground beef.
AB  - Lactobacillus sakei is a lactic acid bacterium, naturally associated with long
      term storage of fresh meat at low temperature. Here we investigated the effect,
      on the evolution of pathogenic and spoilage microorganisms in ground beef, of L.
      sakei cocktails used as bioprotective cultures. We selectively developed a real
      time quantitative PCR method, allowing the quantification of individual L. sakei
      strains inoculated in ground meat with specific probes. Six cocktails of three
      strains were tested to evaluate their effect on the growth of Salmonella enterica
      Typhimurium, Escherichia coli O157:H7 and Brochothrix thermosphacta at 4 degrees
      C and 8 degrees C, under vacuum or modified atmosphere packaging. Using plating
      methods to quantify the different bacterial species, one cocktail showed an
      effect against S. Typhimurium and E. coli under given conditions. Real time
      quantitative PCR showed that the three inoculated L. sakei strains had a
      different growth pattern, and that the association of these three strains indeed
      impaired growth of S. Typhimurium and E. coli. 

PMID- 24041593
TI  - Under multilevel selection: "when shall you be neither spiteful nor envious?".
AB  - In this paper, we study the egalitarianism-game in multilevel selection
      situation. The individuals form reproductive groups. In each group, an
      egalitarianism-game determines the number of juveniles of different phenotypes
      (spiteful, envious, neutral and donator). Before the juveniles form the next
      reproductive group, they have to survive either predators' attacks or a fight
      between two groups. We adopt the ESS definition of Maynard Smith to multilevel
      selection. Based on the "group size advantage" assumption (which claims that each
      juvenile's survival rate depends on the size of his own group, supposing that
      either the survival rate under predators' attacks is higher in larger groups, or
      in inter-group aggression usually the larger group wins) we found that when the
      survival probability has a massive effect on the average fitness, then "group
      fitness maximizing behavior" (in our case, either neutral or donator) has
      evolutionary advantage over "competitive behavior" (in our case, either spiteful
      or envious). 

PMID- 24041592
TI  - Reproductive isolation revealed in preliminary crossbreeding experiments using
      field collected Triatoma dimidiata (Hemiptera: Reduviidae) from three ITS-2
      defined groups.
AB  - Triatoma dimidiata, a Chagas disease vector distributed in Mexico, Central
      America, Colombia, Venezuela, Peru and Ecuador, has been studied using genetic
      markers and four groups have been defined by ITS-2 sequences: 1A, 1B, 2 and 3. To
      gather evidence on the divergence and reproductive isolation among T. dimidiata
      ITS-2 groups, we carried out 15 crossbreeding experiments with field-collected
      sylvan and domestic T. dimidiata from Guatemala where three groups are found: 1A,
      2 and 3. Reciprocal crosses between individuals from groups 1A and 2, and a cross
      between group 2 individuals from different habitats, produced an average 129.78+/
      42.29 eggs with hatching success ranging from 31.6 to 90.1%. The offspring of
      these crosses reached the adult stage, and crosses between F1 insects produced
      eggs. These results suggest that there are no pre- or post-zygotic reproductive
      barriers between groups 1A and 2, or within group 2. Crosses between group 3
      females and males from groups 1A or 2 produced on average 85.67+/-30.26 eggs and
      none of them hatched. These results support the existence of pre-zygotic barriers
      between T. dimidiata group 3 and groups 1A and 2. The group 3 individuals were
      collected in sylvatic environments in Yaxha, Peten, Guatemala. Previously,
      distinct chromosomal characteristics (cytotype 3) were described in individuals
      from this population. Based on this evidence we suggest that this population is
      divergent at the species level from other T. dimidiata populations. 

PMID- 24041594
TI  - Phenotypic plasticity with instantaneous but delayed switches.
AB  - Phenotypic plasticity is a widespread phenomenon, allowing organisms to better
      adapt to changing environments. Most empirical and theoretical studies are
      restricted to irreversible plasticity where the expression of a specific
      phenotype is mostly determined during development. However, reversible plasticity
      is not uncommon; here, organisms are able to switch back and forth between
      phenotypes. We present two optimization models for the fitness of (i) non
      plastic, (ii) irreversibly plastic, and (iii) reversibly plastic genotypes in a
      fluctuating environment. In one model, the fitness values of an organism during
      different life phases act together multiplicatively (so as to consider traits
      that are related to survival). The other model additionally considers additive
      effects (corresponding to traits related to fecundity). Both models yield
      qualitatively similar results. If the only costs of reversible plasticity are due
      to temporal maladaptation while switching between phenotypes, reversibility is
      virtually always advantageous over irreversibility, especially for slow
      environmental fluctuations. If reversibility implies an overall decreased
      fitness, then irreversibility is advantageous if the environment fluctuates
      quickly or if stress events last relatively short. Our results are supported by
      observations from different types of organisms and have implications for many
      basic and applied research questions, e.g., on invasive alien species. 

PMID- 24041595
TI  - Embryonic hematopoiesis.
AB  - Blood cells are continually produced from a pool of progenitors that derive from
      hematopoietic stem cells (HSCs). In vertebrates, the hematopoietic system
      develops from two distinct waves or generation of precursors. The first wave
      occurs in the yolk sac, in mammals or equivalent embryonic structure, and
      produces nucleated primitive erythrocytes that provide the embryo with the first
      oxygen transporter and are, therefore, essential for the viability of the embryo.
      The yolk sac also produces myeloid cells that migrate to the central nervous
      system and to the skin to form the microglia and skin specific macrophages, the
      Langerhans cells. The second wave occurs in the dorsal aorta and produces
      multipotential hematopoietic progenitors. These cells are generated once in the
      lifetime from mesoderm derivatives closely related to endothelial cells, during a
      short period of embryonic development. Newly generated cells do not reconstitute
      the hematopoietic compartment of conventional recipients; therefore, they are
      designated as immature or pre-HSCs. They undergo maturation into adult HSCs in
      the aorta or in the fetal liver accompanied by the expression of MHC class I,
      CD45, CD150, Sca-1 and the absence of CD48. Differentiation of HSCs first occurs
      in the fetal liver, giving rise to mature blood cells. HSCs also expand in the
      fetal liver, and in a short time period (four days in the mouse embryo), they
      increase over 40-fold. HSCs and progenitor cells exit the fetal liver and
      colonize the spleen, where differentiation to the myeloid lineage and particular
      lymphoid subsets is favored. 

PMID- 24041597
TI  - Iron chelation therapy for non-transfusion-dependent thalassemia (NTDT): a status
      quo.

PMID- 24041598
TI  - Evolution of bicycle helmet use and its determinants in France: 2000-2010.
AB  - This paper aims to analyse helmet use in France, as a voluntary behaviour rather
      than a legal requirement, promoted by public awareness campaigns. It aims to
      investigate the determinants of helmet wearing and to explore its evolution from
      2000 to 2010. The analysis relies on data from a series of general population
      surveys called "Health Barometers": 2000 (n=13,163), 2005 (n=25,651) and 2010
      (n=8573). Multivariate logistic regressions were used to identify factors
      associated with helmet use and time trends. Nearly half of the 15-75 year olds
      surveyed reported that they rode a bicycle, and among these cyclists, 22.0%
      reported that they wore a helmet on their last ride. Further analysis by gender
      reveals that twice as many men than women wore helmets. Over the last decade,
      helmet use among cyclists has clearly increased, from 7.3% in 2000 to 22.0% in
      2010, whereas the influence of social and economic factors, such as unemployment
      and wage disparities, appears to have decreased. Several determinants of bicycle
      helmet use were highlighted. To improve the effectiveness of further public
      information campaigns on helmet use, the key target groups should include women,
      under 25 year olds and people living in urban areas. Promoting the wearing of
      helmets among families should also be enhanced, given the higher rate of helmet
      use by parents as well as children. 

PMID- 24041596
TI  - DNA damage response, redox status and hematopoiesis.
AB  - The ability of hematopoietic stem cells (HSCs) to self-renew and differentiate
      into progenitors is essential for homeostasis of the hematopoietic system. The
      longevity of HSCs makes them vulnerable to accumulating DNA damage, which may be
      leukemogenic or result in senescence and cell death. Additionally, the ability of
      HSCs to self-renew and differentiate allows DNA damage to spread throughout the
      hematologic system, leaving the organism vulnerable to disease. In this review we
      discuss cell fate decisions made in the face of DNA damage and other cellular
      stresses, and the role of reactive oxygen species in the long-term maintenance of
      HSCs and their DNA damage response. 

PMID- 24041599
TI  - Investigation of residual fluoroquinolones in a soil-vegetable system in an
      intensive vegetable cultivation area in Northern China.
AB  - One of the largest vegetable cultivation field sites in Northeast China was
      selected to investigate the occurrence and distribution pattern of
      fluoroquinolones (FQs) in the soil-vegetable system. A total of 100 surface soil
      samples and 68 vegetable samples were collected from this study area. The
      antibiotic concentration was analyzed using high-performance liquid
      chromatography tandem mass spectrometry. Results indicated the presence of FQs in
      all soil samples. Ciprofloxacin (CIP) had the highest mean concentration, at
      104.4 MUg . kg(-1) in the soil, a level that represents a relatively high risk to
      the environment and to human health. However, in the vegetable samples,
      norfloxacin (NOR) was significantly higher than CIP and enrofloxacin (ENR),
      ranging from 18.2 to 658.3 MUg . kg(-1). The transfer ability of NOR in soil
      vegetables is greater than that of CIP and ENR. Moreover, we found that the
      solanaceous fruits had a higher antibiotic accumulation ability than the leafy
      vegetables. Taken together, these data indicate that greater attention should be
      paid to the region in which vegetables with higher accumulation ability are
      grown.

PMID- 24041600
TI  - Canadian boreal pulp and paper feedstocks contain neuroactive substances that
      interact in vitro with GABA and dopaminergic systems in the brain.
AB  - Pulp and paper wood feedstocks have been previously implicated as a source of
      chemicals with the ability to interact with or disrupt key neuroendocrine
      endpoints important in the control of reproduction. We tested nine Canadian
      conifers commonly used in pulp and paper production as well as 16 phytochemicals
      that have been observed in various pulp and paper mill effluent streams for their
      ability to interact in vitro with the enzymes monoamine oxidase (MAO), glutamic
      acid decarboxylase (GAD), and GABA-transaminase (GABA-T), and bind to the
      benzodiazepine-binding site of the GABA(A) receptor (GABA(A)-BZD). These
      neuroendocrine endpoints are also important targets for treatment of neurological
      disorders such as anxiety, epilepsy, or depression. MAO and GAD were inhibited by
      various conifer extracts of different polarities, including major feedstocks such
      as balsam fir, black spruce, and white spruce. MAO was selectively stimulated or
      inhibited by many of the tested phytochemicals, with inhibition observed by a
      group of phenylpropenes (e.g. isoeugenol and vanillin). Selective GAD inhibition
      was also observed, with all of the resin acids tested being inhibitory. GABA(A)
      BZD ligand displacement was also observed. We compiled a table identifying which
      of these phytochemicals have been described in each of the species tested here.
      Given the diversity of conifer species and plant chemicals with these specific
      neuroactivities, it is reasonable to propose that MAO and GAD inhibition reported
      in effluents is phytochemical in origin. We propose disruption of these
      neuroendocrine endpoints as a possible mechanism of reproductive inhibition, and
      also identify an avenue for potential research and sourcing of conifer-derived
      neuroactive natural products. 

PMID- 24041601
TI  - A novel approach to modeling the reaction kinetics of tetracycline antibiotics
      with aqueous ozone.
AB  - Tetracycline antibiotics represent one of the most successful classes of
      pharmaceuticals and are extensively used around the world for human and
      veterinary health. Ozone-based processes have emerged as a selective water
      treatment process for many pharmaceuticals. The primary objective of this study
      was to determine the reaction kinetics for transformation of five tetracycline
      antibiotics (i.e., chlortetracycline, doxycycline, oxytetracycline,
      rolitetracycline, and tetracycline) by ozone across the pH2 to 9 range. The
      apparent second-order rate constant for tetracycline was on the order of 1-6 *
      10(4) M(-1) s(-1) at low pH, and 0.6-2.0 * 10(6) M(-1) s(-1) at near neutral pH.
      The apparent second-order rate constants did not fit a conventional pKa-based
      model, presumably due to the complex acid/base speciation of tetracycline
      antibiotics. A model that considers the net charge on tetracycline molecules in
      solution provided a nice fit to experimental data for all five tetracyclines. The
      five tetracycline antibiotics demonstrated similar reaction kinetics with ozone,
      and a cumulative analysis of all kinetics data provides a baseline model for
      other tetracycline compounds. The ozone exposure required for complete
      transformation of tetracycline antibiotics (10(-5) M-s) is well below that
      achieved during ozone disinfection processes (10(-3) M-s), indicating that ozone
      is an effective treatment for tetracycline antibiotics.

PMID- 24041602
TI  - Assessing suspended sediment dynamics in relation to ecological thresholds and
      sampling strategies in two Irish headwater catchments.
AB  - Prediction of the impact of suspended sediment on aquatic ecosystems requires
      adequate knowledge of sediment dynamics in surface waters. Often, studies
      reporting the response of aquatic biota to suspended sediment are concerned with
      concentrations, while catchment erosion studies often report sediment delivery as
      annual loads and yields, making the comparison to documented ecological impacts
      difficult. Similarly, the European Union Freshwater Fish Directive (FFD)
      (78/659/EC) stipulates a guideline value of 25 mg l(-1) which should not be
      exceeded, with the exception of floods and droughts. In this respect, the
      significance of suspended sediment in two Irish rivers was assessed using
      turbidity sensors calibrated for suspended sediment. Sediment yields of 0.07
      tonnes (t) ha(-1) year(-1) and 0.44 t ha(-1) year(-1) and annual FFD exceedance
      frequency of 8.3% and 17.8% were estimated for the two catchments. Contrasts in
      the frequency of exceedance events between both catchments was observed, yet
      duration was typically short (<5h). Additionally, this study evaluated different
      sampling resolutions to assess the impact on estimated loads and exceedance
      frequency. Increasing resolution improved accuracy and reduced uncertainty, with
      the 24-7 'Plynlimon' sampling method (sampling every 7h) providing the best
      solution to estimating both loads and exceedance. This study documents some of
      the first data on sediment dynamics in Ireland and indicates that periods of
      elevated suspended sediment concentration in the two study catchments may be
      significant.

PMID- 24041603
TI  - Is the transformation/dissolution protocol suitable for ecotoxicity assessments
      of inorganic substances such as silica fume?
AB  - Performing ecotoxicity tests on poorly water soluble substances and in particular
      metals, metalloids, and metal oxides such as silica fume, can be problematic.
      Such substances may not be directly toxic to aquatic organisms but often have
      high concentrations of impurities present, due to production processes, which may
      result in ecotoxicological effects. This combined with possibly testing above the
      limit of solubility further exacerbates the interpretation of ecotoxicity test
      results. One approach to overcome this is to perform a transformation/dissolution
      (T/D) test to determine the quantities of elemental impurities which will
      consequently be in solution. These data can subsequently be compared to existing
      data to determine if there is likely to be an effect on aquatic organisms. This
      paper highlights research into determining the T/D potential of 2 different
      grades of amorphous silica fume (low and high grade purity) with complementary
      chronic ecotoxicity tests of the 2 substances to validate this approach. The low
      grade silica fume test substance was identified in the T/D assessments as being
      of concern for the potential to cause acute toxicity to aquatic organisms and had
      levels of impurities (e.g. Pb and Zn) in the solutions which exceeded the effect
      limits identified in the open literature. Consequently, silica fume would be
      hazard classified as acute 2 according to regulatory classification schemes.
      However, the results of the ecotoxicity hazard validation assessments in a
      Daphnia magna reproduction test and the sediment dwelling organism Chironomus
      riparius indicated that low and high grade silica fumes are not acutely or
      chronically toxic up to and including an initial loading concentration of 100
      mg/L and 1000 mg/kg respectively. Hence, using the T/D test data alone may have
      resulted in a false hazard classification of silica fume (low grade).

PMID- 24041604
TI  - A year-long study of Cryptosporidium species and subtypes in recreational,
      drinking and wastewater from the central area of Spain.
AB  - A year-long longitudinal study was undertaken to evaluate the presence of
      Cryptosporidium spp. in drinking water treatment plants (DWTPs), wastewater
      treatment plants (WWTPs) and freshwater bathing beaches (FBBs) from the central
      area of Spain. Water samples were collected according to USEPA Method 1623, and
      concentrated by the IDEXX Filta-Max(r) system. Cryptosporidium species were
      detected based on PCR-restriction fragment length polymorphism and sequence
      analyses of the ssuRNA gene. C. hominis and/or C. parvum isolates were subtyped
      by DNA sequencing of the Gp60 gene. Among 150 samples, 23 (15.3%) were positive
      by IFAT and 40 (26.7%) by PCR. Cryptosporidium spp. was more frequent in WWTPs
      (26.2 and 50.8%) and FBBs (12.5 and 17.5%) by IFAT and PCR respectively. Effluent
      waters from DWTPs were negative for this parasite suggesting that they are
      suitable for public use. Tertiary treatment in the WWTPs demonstrated a high
      removal efficiency of Cryptosporidium in the samples evaluated. Cryptosporidium
      species identified included C. hominis, C. parvum, C. ubiquitum, C. andersoni and
      C. muris. Subtyping analysis revealed C. hominis IbA10G2 and IeA11G3T3 alleles,
      which is the first report of the latter in water samples. Cryptosporidium highest
      frequency was observed in winter and spring. Our data provide information about
      the occurrence and diversity of Cryptosporidium in water of human use from the
      central area of Spain. 

PMID- 24041605
TI  - Current status, uncertainty and future needs in soil organic carbon monitoring.
AB  - Increasing human demands on soil-derived ecosystem services requires reliable
      data on global soil resources for sustainable development. The soil organic
      carbon (SOC) pool is a key indicator of soil quality as it affects essential
      biological, chemical and physical soil functions such as nutrient cycling,
      pesticide and water retention, and soil structure maintenance. However,
      information on the SOC pool, and its temporal and spatial dynamics is unbalanced.
      Even in well-studied regions with a pronounced interest in environmental issues
      information on soil carbon (C) is inconsistent. Several activities for the
      compilation of global soil C data are under way. However, different approaches
      for soil sampling and chemical analyses make even regional comparisons highly
      uncertain. Often, the procedures used so far have not allowed the reliable
      estimation of the total SOC pool, partly because the available knowledge is
      focused on not clearly defined upper soil horizons and the contribution of
      subsoil to SOC stocks has been less considered. Even more difficult is
      quantifying SOC pool changes over time. SOC consists of variable amounts of
      labile and recalcitrant molecules of plant, and microbial and animal origin that
      are often operationally defined. A comprehensively active soil expert community
      needs to agree on protocols of soil surveying and lab procedures towards reliable
      SOC pool estimates. Already established long-term ecological research sites,
      where SOC changes are quantified and the underlying mechanisms are investigated,
      are potentially the backbones for regional, national, and international SOC
      monitoring programs. 

PMID- 24041606
TI  - Changes in management of acute myocardial infarction over the last 110 years.

PMID- 24041607
TI  - Lower extremities and iliopsoas pyomyositis with concurrent septic arthritis and
      spinal epidural abscess in a diabetic patient.
AB  - Pyomyositis is a rarely encountered infection among diabetics, which usually
      affects lower extremities. Herein, we present a case of lower extremities and
      iliopsoas pyomyositis with concurrent septic arthritis and spinal epidural
      abscess in a patient with poorly controlled diabetes mellitus. 

PMID- 24041608
TI  - Results of speech improvement following simultaneous push-back together with
      velopharyngeal flap surgery in cleft palate patients.
AB  - OBJECTIVE: Velopharyngeal insufficiency (VPI) can be caused by a variety of
      disorders. The most common cause of VPI is the association with cleft palate. The
      aim of this study was to evaluate the effectiveness of different surgical
      techniques for cleft palate patients with VPI: (1) velopharyngoplasty with an
      inferiorly based posterior pharyngeal flap (VPP posterior, Schonborn-Rosenthal),
      and (2) combination of VPP posterior and push-back operation (Dorrance). PATIENTS
      AND METHODS: 41 subjects (26 females, 15 males) with VPI were analysed.
      Hypernasality was judged subjectively and nasalance data were assessed
      objectively using the NasalView system preoperative and 6 months postoperative.
      RESULTS: Subjective analysis showed improved speech results regarding
      hypernasality for all OP-techniques with good results for VPP posterior and VPP
      posterior combined with push-back with success rates of 94.4% and 87.7%,
      respectively. Objective analysis showed a statistically significant reduction of
      nasalance for both VPP posterior and VPP posterior combined with push-back (p <
      0.01). However, there were no statistically significant differences concerning
      measured nasalance values postoperatively between the VPP posterior and VPP
      posterior combined with push-back. CONCLUSION: Based on our findings, both VPP
      posterior and VPP posterior combined with push-back showed good results in
      correction of hypernasality in cleft patients with velopharyngeal insufficiency.

PMID- 24041609
TI  - Osteogenic potential of a chalcone in a critical-size defect in rat calvaria
      bone.
AB  - BACKGROUND: This study describes the bone formation stimulated by the application
      of a type of chalcone to critical-size defects in rat calvarial bone. MATERIAL
      AND METHODS: Sixty female Wistar rats were divided into 6 groups of 10 animals
      per group: control (no treatment), vehicle (vaseline) and the chalcone (1-phenyl
      3-(4-chlorophenyl)-2-propen-1-one) suspended in vaseline at 10%. A critical-size
      defect of 5 mm was prepared using a trephine in the calvarial bone, after which
      the treatment was applied, in a single dose, according to the experimental group.
      The samples were evaluated macroscopically using ImageJ software, and
      histologically 30 and 45 days after surgery. RESULTS: At 30 days after surgery,
      there was significant bone formation (p < 0.05) in the groups treated with
      chalcone, compared with the other groups. Many active osteoblasts were observed
      adjacent to the borders of the newly formed bone tissue. 45 days after surgery in
      the chalcone group, the surgical defects showed complete bone closure.
      CONCLUSION: The results of this study suggest that chalcone has significant
      potential to induce the formation of new bone.

PMID- 24041610
TI  - Quantification of facial asymmetry by 2D analysis - A comparison of recent
      approaches.
AB  - INTRODUCTION: Symmetry has been found to play a crucial role in attractiveness
      assessment and so its restoration is an essential problem in oral maxillofacial
      surgery. This paper presents an overview of recent 2D asymmetry analysis
      techniques. These are techniques which are based on the evaluation of two
      dimensional data, like photos. The aim of this paper is to find the most precise
      and practical techniques to investigate facial asymmetry. MATERIALS AND METHODS:
      For this purpose studies addressing symmetry investigations are collected and
      categorized by the type of data they extract from the photos. The reference
      points on the facial surface, which are frequently used in these studies, are
      presented and calculation methods are described. RESULTS: Three kinds of
      techniques using vertical or horizontal reference lines or centres of bilateral
      points appear to be most appropriate. Recommendations are made, which aspects
      should be taken into account when calculating symmetry/asymmetry indices from
      photos. Advantages and disadvantages of the three selected methods are summarized
      in a table. CONCLUSIONS: Using one of the three recommended approaches denoted by
      FA, AI and z-score allows calculating meaningful asymmetry values. The proper
      selection and identification of reference points is crucial. For highest
      accuracy, a sufficient number of evenly distributed and reproducible reference
      points should be used.

PMID- 24041611
TI  - Bilateral nephrectomy significantly improves health-related quality of life in a
      hemodialysis patient with autosomal dominant polycystic kidney disease.

PMID- 24041613
TI  - Health status of Largescale Sucker (Catostomus macrocheilus) collected along an
      organic contaminant gradient in the lower Columbia River, Oregon and Washington,
      USA.
AB  - The health of Largescale Sucker (Catostomus macrocheilus) in the lower Columbia
      River (USA) was evaluated using morphometric and histopathological approaches,
      and its association with organic contaminants accumulated in liver was evaluated
      in males. Fish were sampled from three sites along a contaminant gradient. In
      2009, body length and mass, condition factor, gonadosomatic index, and hematocrit
      were measured in males and females; liver and gonad tissue were collected from
      males for histological analyses; and organ composites were analyzed for
      contaminant content in males. In 2010, additional data were collected for males
      and females, including external fish condition assessment, histopathologies of
      spleen, kidney and gill and, for males, liver contaminant content. Multivariate
      analysis of variance indicated that biological traits in males, but not females,
      differed among sites in 2009 and 2010. Discriminant function analysis indicated
      that site-related differences among male populations were relatively small in
      2009, but in 2010, when more variables were analyzed, males differed among sites
      in regards to kidney, spleen, and liver histopathologies and gill parasites.
      Kidney tubular hyperplasia, liver and spleen macrophage aggregations, and gill
      parasites were generally more severe in the downstream sites compared to the
      reference location. The contaminant content of male livers was also generally
      higher downstream, and the legacy pesticide hexachlorobenzene and flame
      retardants BDE-47 and BDE-154 were the primary drivers for site discrimination.
      However, bivariate correlations between biological variables and liver
      contaminants retained in the discriminant models failed to reveal associations
      between the two variable sets. In conclusion, whereas certain non-reproductive
      biological traits and liver contaminant contents of male Largescale Sucker
      differed according to an upstream-downstream gradient in the lower Columbia
      River, results from this study did not reveal the specific environmental factors
      responsible for the differences in health status among fish populations. 

PMID- 24041612
TI  - Comparison of associations of urine protein-creatinine ratio versus albumin
      creatinine ratio with complications of CKD: a cross-sectional analysis.
AB  - BACKGROUND: Urine albumin-creatinine ratio (ACR) and protein-creatinine ratio
      (PCR) are important markers of kidney damage and are used for prognosis in
      persons with chronic kidney disease (CKD). Despite how commonly these
      measurements are done in clinical practice, relatively few studies have directly
      compared the performance of these 2 measures with regard to associations with
      clinical outcomes, which may inform clinicians about which measure of urinary
      protein excretion is best. We studied the association of ACR and PCR with common
      complications of CKD. STUDY DESIGN: Cross-sectional study. SETTING &
      PARTICIPANTS: 3,481 participants with CKD in the Chronic Renal Insufficiency
      Cohort (CRIC) Study. PREDICTORS: ACR and PCR. OUTCOMES: We examined the
      association between ACR and PCR with measures of common CKD complications: serum
      hemoglobin, bicarbonate, parathyroid hormone, phosphorus, potassium, and albumin.
      MEASUREMENTS: Restricted cubic spline analyses adjusted for estimated glomerular
      filtration rate (eGFR; calculated by the MDRD [Modification of Diet in Renal
      Disease] Study equation) were performed to study the continuous association with
      our predictors with each outcome. RESULTS: Mean eGFR was 43+/-13 (SD)mL/min/1.73
      m2 and median values for PCR and ACR were 140 and 46 mg/g, respectively. In
      continuous analyses adjusted for eGFR, higher ACRs and PCRs were similar and both
      were associated with lower serum hemoglobin, bicarbonate, and albumin levels and
      higher parathyroid hormone, phosphorus, and potassium levels. Across all
      outcomes, the associations of ACR and PCR were similar, with only small absolute
      differences in the outcome measure. Similar associations were seen in patients
      with diabetes mellitus. LIMITATIONS: Participants largely had moderate CKD with
      low values for ACR and PCR, so results may not be generalizable to all CKD
      populations. CONCLUSIONS: In persons with CKD, ACR and PCR are relatively similar
      in their associations with common complications of CKD. Thus, routine measurement
      of PCR may provide similar information as ACR in managing immediate complications
      of CKD.

PMID- 24041614
TI  - Comparison of in vitro tests for antioxidant and immunomodulatory capacities of
      compounds.
AB  - Oxidative stress is considered to be critically involved in the normal aging
      process but also in the development and progression of various human pathologies
      like cardiovascular and neurodegenerative diseases, as well as of infections and
      malignant tumors. These pathological conditions involve an overwhelming
      production of reactive oxygen species (ROS), which are released as part of an
      anti-proliferative strategy during pro-inflammatory immune responses. Moreover,
      ROS themselves are autocrine forward regulators of the immune response. Most of
      the beneficial effects of antioxidants are considered to derive from their
      influence on the immune system. Due to their antioxidant and/or radical
      scavenging nature, phytochemicals, botanicals and herbal preparations can be of
      great importance to prevent oxidation processes and to counteract the activation
      of redox-regulated signaling pathways. Antioxidants can antagonize the activation
      of T-cells and macrophages during the immune response and this anti-inflammatory
      activity could be of utmost importance for the treatment of above-mentioned
      disorders and for the development of immunotolerance. Herein, we provide an
      overview of in vitro assays for the measurement of antioxidant and anti
      inflammatory activities of plant-derived substances and extracts, by discussing
      possibilities and limitations of these methods. To determine the capacity of
      antioxidants, the oxygen radical absorbance capacity (ORAC) assay and the cell
      based antioxidant activity (CAA) assay are widely applied. To examine the
      influence of compounds on the human immune response more closely, the model of
      mitogen stimulated human peripheral blood mononuclear (PBMC) cells can be
      applied, and the production of the inflammatory marker neopterin as well as the
      breakdown of the amino acid tryptophan in culture supernatants can be used as
      readout to indicate an immunomodulatory potential of the tested compound. These
      two biomarkers of immune system activation are robust and correlate with the
      course of cardiovascular, neurodegenerative and malignant tumor diseases, but
      also with the normal aging process, and they are strongly predictive. Thus, while
      the simpler ORAC and CAA assays provide insight into one peculiar chemical
      aspect, namely the neutralization of peroxyl radicals, the more complex PBMC
      assay is closer to the in vivo conditions as the assay comprehensively enlights
      several properties of immunomodulatory test compounds. 

PMID- 24041615
TI  - Microfluidic growth chambers with optical tweezers for full spatial single-cell
      control and analysis of evolving microbes.
AB  - Single-cell analysis in microfluidic systems has opened up new possibilities in
      biotechnological research enabling us to deal with large eukaryotic cells and
      even small bacteria. In particular, transient investigations in laminar flow or
      diffusive environments can be performed to unravel single cell behaviour. Up to
      now, most systems have been limited with respect to precise cell inoculation and
      sampling methods. Individual cell selection and manipulations have now been made
      possible by combining laser tweezers with microfluidic cell cultivation
      environments specifically tailored for micrometre-sized bacteria. Single cells
      were optically seeded into various micrometre-sized growth sites arranged in
      parallel. During cultivation, single-cell elongation, morphology and growth rates
      were derived from single cells and microcolonies of up to 500 cells. Growth of
      irradiated bacteria was not impaired by minimizing the exposed laser dosage as
      confirmed by exceptional growth rates. In fact, Escherichia coli exhibited
      doubling times of less than 20min. For the first time, a filamentous Escherichia
      coli WT (MG1655) was safely relocated from its growing microcolony by laser
      manipulations. The cell was transferred to an empty cultivation spot allowing
      single-cell growth and morphology investigations. Contrary to previous
      discussions, the filamentous E. coli exhibited normal cell morphology and
      division after a few generations. This combination of optical tweezers and single
      cell analysis in microfluidics adds a new degree of freedom to microbial single
      cell analysis. 

PMID- 24041617
TI  - Primary bone grafting in open fractures with segmental bone loss.

PMID- 24041616
TI  - Cellular location and major terminal networks of the orexinergic system in the
      brain of two megachiropterans.
AB  - The present study describes the distribution of orexin-A immunoreactive neurons
      and their terminal networks in the brains of two species of megachiropterans. In
      general the organization of the orexinergic system in the mammalian brain is
      conserved across species, but as one of two groups of mammals that fly and have a
      high metabolic rate, it was of interest to determine whether there were any
      specific differences in the organization of this system in the megachiropterans.
      Orexinergic neurons were limited in distribution to the hypothalamus, and formed
      three distinct clusters, or nuclei, a main cluster with a perifornical location,
      a zona incerta cluster in the dorsolateral hypothalamus and an optic tract
      cluster in the ventrolateral hypothalamus. The nuclear parcellation of the
      orexinergic system in the megachiropterans is similar to that seen in many
      mammals, but differs from the microchiropterans where the optic tract cluster is
      absent. The terminal networks of the orexinergic neurons in the megachiropterans
      was similar to that seen in a range of mammalian species, with significant
      terminal networks being found in the hypothalamus, cholinergic pedunculopontine
      and laterodorsal tegemental nuclei, the noradrenergic locus coeruleus complex,
      all serotonergic nuclei, the paraventricular nuclei of the epithalamus and
      adjacent to the habenular nuclei. While the megachiropteran orexinergic system is
      typically mammalian in form, it does differ from that reported for
      microchiropterans, and thus provides an additional neural character arguing for
      independent evolution of these two chiropteran suborders. 

PMID- 24041619
TI  - India's "tryst" with universal health coverage: reflections on ethnography in
      Indian health policymaking.
AB  - In 2011, India stood at the crossroads of potentially major health reform. A High
      Level Expert Group (HLEG) on universal health coverage (UHC), convened by the
      Indian Planning Commission, proposed major changes in the structure and
      functioning of the country's health system. This paper presents reflections on
      the role of ethnography in policy-based social change for health in India,
      drawing from year-long participation in the aforementioned policy development
      process. It theorizes that international discourses have been (re)appropriated in
      the Indian case by recourse to both experience and evidence, resulting in a
      plurality of concepts that could be prioritized for Indian health reform. This
      articulation involved HLEG members exerting para-ethnographic labour and paying
      close attention to context, suggesting that ethnographic sensibilities can reside
      within the interactive and knowledge production practices among experts oriented
      toward policy change. 

PMID- 24041618
TI  - Combination of arsenic trioxide and chemotherapy in small cell lung cancer.
AB  - INTRODUCTION: Small cell lung cancer (SCLC) carries high mortality despite
      standard chemotherapy. Arsenic trioxide (ATO) has demonstrated clinical efficacy
      in leukemia and in vitro activity in various solid tumors. This study was
      conducted to determine the in vitro and in vivo combination effects of ATO and
      chemotherapy in SCLC. MATERIALS AND METHODS: The in vitro model consisted of 5
      SCLC cell lines (H187, H526, H69, H841 and DMS79) and the anti-proliferative
      effects of ATO, cisplatin, etoposide or combinations thereof were measured.
      Synergism was determined by calculation of the combination index (CI) according
      to Chou and Talalay. Assays for apoptosis, intracellular glutathione (GSH)
      content, and mitochondrial membrane depolarization (MMD) were performed. Arsenic
      content was measured by inductively coupled plasma-mass spectrometry. Expression
      level of MRP1, MRP2 and pH2AX was detected by Western blot while cellular pH2AX
      level was monitored by immunofluorescent staining. An in vivo xenograft model in
      nude mice was established with a H841 cell line to test the effects of drug
      combinations. RESULTS: All 5 SCLC cell lines were sensitive to ATO, with IC(50)
      values (48 h) 1.6-8 MUM. Synergistic or additive effects were obtained by
      combining cisplatin with ATO in all 5 cell lines. Combination of etoposide with
      ATO resulted in antagonistic or barely additive effects. Apoptotic assays and
      pH2AX immunofluorescent staining corroborated the synergistic combination of ATO
      and cisplatin. In addition, the ATO/cisplatin combination enhanced MMD, depleted
      GSH, downregulated MRP2 and elevated intracellular ATO content compared with
      either ATO or cisplatin alone. In vivo combination of ATO and cisplatin also
      demonstrated synergism in the H841 xenograft model. CONCLUSIONS: There was
      clinically relevant in vitro activity of ATO in a panel of 5 SCLC cell lines.
      Significant synergism was demonstrated with the ATO/cisplatin combination, while
      antagonism was noted with the ATO/etoposide combination in both in vitro and in
      vivo models.

PMID- 24041620
TI  - Endothelial PAS domain protein 1 Chr2:46441523(hg18) polymorphism is associated
      with susceptibility to high altitude pulmonary edema in Han Chinese.
AB  - OBJECTIVE: The purpose of this study was to test the hypothesis that
      polymorphisms in the endothelial PAS domain protein 1 (EPAS1) gene are associated
      with the susceptibility to high altitude pulmonary edema (HAPE) in Han Chinese.
      METHODS: This study enrolled 153 HAPE patients (HAPE-p), matched with Han Chinese
      resistant to HAPE (HAPE-r) and local highland Tibetans from Yushu earthquake
      construction population in Qinghai where the altitude is more than 3500 m above
      sea level. The polymorphism of EPAS1 chr2:46441523(hg18) was genotyped by
      polymerase chain reaction restriction fragment length polymorphism and confirmed
      by DNA sequencing. RESULTS: The frequencies of EPAS1 chr2:46441523(hg18)
      polymorphism C allele were significantly higher in the HAPE-p group than in the
      HAPE-r group (P < .001), but the frequencies of heterozygous C/G were
      significantly higher in the HAPE-r group than in the HAPE-p group (P < .001).
      Moreover, the frequencies of the EPAS1 chr2:46441523(hg18) polymorphism G allele
      were significantly higher in the highland Tibetan group than in the HAPE-p and
      HAPE-r groups. CONCLUSIONS: The EPAS1 chr2:46441523(hg18) polymorphism C is
      strongly associated with susceptibility to HAPE in Han Chinese, and the EPAS1
      chr2:46441523(hg18) polymorphism G is present at high frequency and may be
      associated with high altitude adaptation in the Tibetans.

PMID- 24041621
TI  - Retrieval of additional epinephrine from auto-injectors.
AB  - Anaphylaxis is a challenging condition for any austere environment. It is
      unpredictable, has sudden onset and a high fatality rate, and is responsive only
      to epinephrine, a prescription medication. The Wilderness Medical Society has
      formally recommended that non-medical providers working in austere environments
      be trained to administer epinephrine. Medical providers frequently prescribe auto
      injectors for this purpose due to their ease of use by nonmedical providers.
      However, auto-injectors have limitations in the wilderness environment,
      particularly due to their single-dose (or at most 2-dose) design. This paper
      describes an austere environment technique for obtaining multiple additional
      doses of epinephrine from auto-injectors that have already been used as designed.

PMID- 24041622
TI  - Fear of missing out--a tribute to Zach Orman.

PMID- 24041623
TI  - Energy expenditure and intensity levels during a 6170-m summit in the Karakoram
      Mountains.
AB  - OBJECTIVE: Although the majority of high altitude studies have used doubly
      labeled water to assess energy expenditure (EE), minimal research has examined
      variation in intensity levels while participating in such an expedition. The
      purpose of this study was to use ambulatory monitoring technology to assess EE
      and time spent in moderate (3.0-6.0 METS), vigorous (6.0-9.0 METS), and very
      vigorous (>9.0 METS) intensities during an expedition to summit a 6170-m peak in
      Northern Pakistan. METHODS: Twelve men and 2 women were studied. Their EE was
      determined from galvanic skin response, heat flux, and biaxial accelerometry
      using a multisensor armband. Lake Louise Scores for altitude illness assessment
      were obtained each morning. RESULTS: Average daily total EE and number of steps
      taken was 4173 +/- 848 kcal/d (range, 3332 to 4838 kcal/d) and 26,232 +/- 7210
      steps/d (range, 11,788 to 34,979 steps/d), respectively. On average, subjects
      spent approximately 7.7 h/d performing physical activity (>3.0 METS). Of this,
      subjects spent 399 +/- 107, 61 +/- 77, and 3 +/- 10 min/d at moderate, vigorous,
      and very vigorous intensity levels, respectively, corresponding to 88%, 11%, and
      1% of total physical activity time. During summit day, subjects climbed at an
      intensity equivalent to approximately 42% of their high altitude predicted
      maximal oxygen consumption at 5100 m). CONCLUSIONS: During a high altitude
      expedition, subjects predominantly exercise at a moderate intensity, with limited
      time spent at higher intensity levels. Use of accelerometer-based technology may
      provide more cost-effective and logistically easier means of assessing EE in
      extreme environments.

PMID- 24041624
TI  - Metabolic impact assessment for heterologous protein production in Streptomyces
      lividans based on genome-scale metabolic network modeling.
AB  - The metabolic impact exerted on a microorganism due to heterologous protein
      production is still poorly understood in Streptomyces lividans. In this present
      paper, based on exometabolomic data, a proposed genome-scale metabolic network
      model is used to assess this metabolic impact in S. lividans. Constraint-based
      modeling results obtained in this work revealed that the metabolic impact due to
      heterologous protein production is widely distributed in the genome of S.
      lividans, causing both slow substrate assimilation and a shift in active
      pathways. Exchange fluxes that are critical for model performance have been
      identified for metabolites of mouse tumor necrosis factor, histidine, valine and
      lysine, as well as biomass. Our results unravel the interaction of heterologous
      protein production with intracellular metabolism of S. lividans, thus, a possible
      basis for further studies in relieving the metabolic burden via metabolic or
      bioprocess engineering. 

PMID- 24041625
TI  - Recreational water quality response to a filtering barrier at a Great Lakes
      beach.
AB  - Recent research has sought to determine the off- or onshore origin of fecal
      indicator bacteria (FIB) in order to improve local recreational water quality. In
      an effort to reduce offshore contamination, a filtering barrier (FB) was
      installed at Calumet Beach, Lake Michigan, Chicago, IL. A horseshoe-shaped
      curtain (146 m long, 0.18 mm apparent opening size, 1.5-1.6 m deepest point) was
      designed to exclude FIB containing or promoting debris and thus reduce the number
      of swimming advisories during the examination period of July through September
      2012. Mean water Escherichia coli concentrations were significantly lower at
      southern transects (S; outside FB) than at transects within the FB (WN) and at
      northern transects (N; outside FB) (1.45 log (MPN)/100 ml vs. 1.74 and 1.72,
      respectively, p < 0.05, n = 234). Turbidity was significantly higher at the WN
      transects (p < 0.001, n = 233), but it tended to increase throughout the sampling
      season within and outside the FB. E. coli in adjacent foreshore sand was
      significantly lower at the WN transects. A combination of factors might explain
      higher E. coli and turbidity within the FB including increased sediment
      resuspension, trapped algae, shallowing within the FB, and large lake
      hydrodynamic processes. This remediation approach may find better use in a
      different hydrodynamic setting, but the results of this experiment provide
      insight on sources of contamination and nearshore dynamics that may direct future
      beach management strategies. 

PMID- 24041626
TI  - Kinetics of cadmium(II) uptake by mixed maghemite-magnetite nanoparticles.
AB  - In the present study, batch adsorption experiments involving the adsorption of
      Cd(II) ions from aqueous solutions have been carried out using mixed maghemite
      magnetite as adsorbent. The uptake capacity of Cd(II) ions by mixed maghemite
      magnetite increased with an increase in the pH of the adsorbate solution. An
      increase in adsorbent dosage increased Cd(II) removal but decreased adsorption
      capacity and it was found to follow the pseudo-second-order model. Cd removal
      from a solution containing 1.5 mg/L initial concentration of Cd(II) decreased
      from 1.9 to 1.3 mg/g upon increasing the temperature from 10 to 50  degrees C.
      Cadmium adsorption may be partly diffusion controlled and partly due to
      electrostatic effect along with specific adsorption involving the adsorption of
      Cd(++) and CdOH(+) on mixed maghemite-magnetite nanoparticles in the alkaline pH
      range. X-ray photoelectron spectroscopy (XPS) surveys confirmed that Cd(2+) ions
      may undergo oxidation-reduction reactions upon exposure to mixed maghemite
      magnetite, or may be fixed by complexation to oxygen atoms in the oxyhydroxy
      groups at the surface of the iron oxide nanoparticles. After Cd(II) adsorption by
      the maghemite-magnetite mixture, the percent maghemite decreased from 74.8 to
      68.5%. 

PMID- 24041627
TI  - The five "Ws" for bone pain due to the administration of granulocyte-colony
      stimulating factors (G-CSFs).
AB  - Granulocyte-colony stimulating factors (G-CSFs) are commonly employed in clinical
      practice. The most relevant adverse event of G-CSF administration is bone pain.
      Approximately 20% of cancer patients experienced bone pain with the
      administration of prophylactic daily G-CSFs (lenograstim and filgrastim). The
      reported incidence of bone pain in cancer patients undergoing pegfilgrastim
      prophylaxis ranged from 25% to 38%. In healthy donors the incidence of bone pain
      was higher than in cancer patients, ranging from 52% to 84%. There are four main
      causes of G-CSF related bone pain: bone marrow quantitative and qualitative
      expansion, peripheral nociceptor sensitization to nociceptive stimuli, modulation
      of immune function and direct effect on bone metabolism. For the prevention and
      treatment of bone pain occurring after or during GCSFs administration,
      acetaminophen and nonsteroidal anti-inflammatory agents are commonly used as
      first-line treatment; antihistamines, opioids and dose reduction of G-CSFs are
      considered as second line therapy. The only randomized clinical trial conducted
      for the prevention and treatment of G-CSF induced bone pain showed the efficacy
      of naproxen in reducing the incidence, the severity and the duration of bone pain
      induced by the administration of pegfilgrastim.

PMID- 24041628
TI  - Drug interactions with solid tumour-targeted therapies.
AB  - Drug interactions are an on-going concern in the treatment of cancer, especially
      when targeted therapies, such as tyrosine kinase inhibitors (TKI) or mammalian
      target of rapamycin (mTOR) inhibitors, are being used. The emergence of elderly
      patients and/or patients with both cancer and other chronic co-morbidities leads
      to polypharmacy. Therefore, the risk of drug-drug interactions (DDI) becomes a
      clinically relevant issue, all the more so as TKIs and mTOR inhibitors are
      essentially metabolised by cytochrome P450 enzymes. These DDIs can result in
      variability in anticancer drug exposure, thus favouring the selection of
      resistant cellular clones or the occurrence of toxicity. This review provides a
      comprehensive overview of DDIs that involve targeted therapies approved by the
      FDA for the treatment of solid tumours for more than 3 years (sorafenib,
      sunitinib, erlotinib, gefitinib, imatinib, lapatinib, everolimus, temsirolimus)
      and medicinal herb or drugs. This review also provides some guidelines to help
      oncologists and pharmacists in their clinical practice.

PMID- 24041629
TI  - Pazopanib a tyrosine kinase inhibitor with strong anti-angiogenetic activity: a
      new treatment for metastatic soft tissue sarcoma.
AB  - Soft tissue sarcomas (STS) are rare tumors with mesenchymal origin, accounting
      for 1% of all human cancer. Local control of STS can be obtained through the use
      of surgery and radiotherapy. In about 40% of these patients, disease will recur
      at distant sites, and of these more than 90% will die because of this aggressive
      malignancy. In advanced and/or metastatic STS patients treated with anthracycline
      based regimen the median overall survival is about 12 months, and it has remained
      unchanged during the last 20 years. Clearly, this strongly suggests the need for
      discover more active compounds in STS, such as imatinib in GIST or
      dermatofibrosarcoma patients. In this paper we describe the crucial role of
      angiogenesis mechanisms in sarcomas development and progression. Consequentially,
      we focus on pazopanib, a novel multitargeted tyrosine kinase inhibitor with anti
      angiogenic activity, mainly due to VEGFR2 pathway interference. We also analyze
      principal completed trials leading pazopanib approval in sarcomas pretreated
      patients. 

PMID- 24041630
TI  - Are erlotinib and gefitinib interchangeable, opposite or complementary for non
      small cell lung cancer treatment? Biological, pharmacological and clinical
      aspects.
AB  - Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR)
      tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC
      patients. These drugs target one of the most important pathways in lung
      carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction',
      with different efficacy according to EGFR gene mutational status in tumor
      samples. Gefitinib has been approved only for EGFR mutation bearing patients
      regardless the line of treatment, while erlotinib is also indicated in patients
      without EGFR mutation who undergo second- or third-line treatment. Some studies
      evaluated the main differences between these drugs both for direct comparison and
      to improve their sequential use. In particular, toxicity profile resulted
      partially different, and these observations may be explained by several molecular
      and pharmacokinetic features. Therefore, this review integrates preclinical data
      with clinical evidences of TKIs to guide the optimization of currently available
      treatments in advanced NSCLC patients. 

PMID- 24041631
TI  - Non-enveloped virus reduction with quaternized chitosan nanofibers containing
      graphene.
AB  - Membranes are an accepted technology for water purification. Membrane filtration
      can remove pathogens, including bacteria and viruses, by size. For small viruses
      that can have a diameter <25nm, removal by size leads to large membrane areas,
      high transmembrane pressures, low water flux, and frequent changing of membranes.
      In this work, we discovered that electrospun nanofibers made of chitosan and
      functionalized with a quaternary amine (HTCC) have the ability to adsorb a model
      non-enveloped virus, porcine parvovirus (PPV). To improve the virus removal of
      HTCC, we added graphene. Graphene both enhanced the ability to form nanofibers
      with HTCC and improved the virus removal. The hydrophobicity of graphene and the
      high charge of the HTCC create a system that can bind 95% of PPV. The
      HTCC/graphene nanofibers could be incorporated into microfiltration membranes and
      remove virus by adsorption. This would create a low pressure system that is more
      likely to benefit areas in need of fresh water. 

PMID- 24041632
TI  - Synthesis of Leonosides E and F derived from Leonurus japonicas Houtt.
AB  - Leonosides E and F, two natural phenylethanoid glycosides derived from Leonurus
      japonicas Houtt, which bear different trisaccharide moieties-one linear and one
      branched, were totally synthesized via a direct transglycosylation strategy.
      After trisaccharyl trichloroacetimidates 3 and 4 were prepared as glycosyl
      donors, they were coupled with the homovanillyl aglycon via silver triflate
      promoted transglycosylation to successfully furnish the fully protected
      glycosides, which were globally deprotected to afford the target molecules in
      6.77% and 10.08% overall yields for the longest linear synthetic sequence
      starting from 6 and 14. 

PMID- 24041633
TI  - Evaluation of the case method in nursing education.
AB  - The case based learning (CBL) is a problem-based learning which engaging students
      and presenting them with learning-related and cognitive challenges. The purpose
      of the study was to elucidate nursing students experiences of the CBL as an
      educational tool in order to find out if it supports their learning. Qualitative
      content analysis was used and performed on the statements from nursing students'
      course evaluations. Students perceived the CBL as an approach combining theory
      with practice which provides an overview of upcoming profession. Students gain
      adequate knowledge about patient care in reality and thereby enabling them to
      obtain a holistic understanding of patients health problems. Reflections related
      to case seminars widen students perspectives, improve their capacity for
      cooperation and help them to achieve long-lasting knowledge. This learning method
      offers nursing students an opportunity to enhance their judgement and critical
      thinking skills by applying theory in practice. Students gain adequate knowledge
      about patient care which may benefit patient care due to students acting
      professionally in their future role. 

PMID- 24041634
TI  - Cost-effectiveness of pharmacist-participated warfarin therapy management in
      Thailand.
AB  - INTRODUCTION: Although pharmacist-participated warfarin therapy management (PWTM)
      is well established, the economic evaluation of PWTM is still lacking
      particularly in Asia-Pacific region. The objective of this study was to estimate
      the cost-effectiveness of PWTM in Thailand using local data where available.
      METHODS: A Markov model was used to compare lifetime costs and quality-adjusted
      life years (QALYs) accrued to patients receiving warfarin therapy through PWTM or
      usual care (UC). The model was populated with relevant information from both
      health care system and societal perspectives. Input data were obtained from
      literatures and database analyses. Incremental cost-effectiveness ratios (ICERs)
      were presented as year 2012 values. A base-case analysis was performed for
      patients at age 45 years old. Sensitivity analyses including one-way and
      probabilistic sensitivity analyses were constructed to determine the robustness
      of the findings. RESULTS: From societal perspective, PWTM and UC results in 39.5
      and 38.7 QALY, respectively. Thus, PWTM increase QALY by 0.79, and increase costs
      by 92,491 THB (3,083 USD) compared with UC (ICER 116,468 THB [3,882.3 USD] per
      QALY gained). While, from health care system perspective, PWTM also results in
      0.79 QALY, and increase costs by 92,788 THB (3,093 USD) compared with UC (ICER
      116,842 THB [3,894.7 USD] per QALY gained). Thus, PWTM was cost-effective
      compared with usual care, assuming willingness-to-pay (WTP) of 150,000 THB/QALY.
      Results were sensitive to the discount rate and cost of clinic set-up.
      CONCLUSION: Our finding suggests that PWTM is a cost-effective intervention.
      Policy-makers may consider our finding as part of information in their decision
      making for implementing this strategy into healthcare benefit package. Further
      updates when additional data available are needed.

PMID- 24041635
TI  - The role of fibrin matrices and tissue factor in early-term trophoblast
      proliferation and spreading.
AB  - INTRODUCTION: Fibrin deposition in placenta is a common phenomenon which can be
      triggered by villous injury and coagulation activation. Fibrin abnormalities
      (hypo/dysfibrinogenemia) and factor XIII deficiency are associated with
      infertility and pregnancy loss. While trophoblasts are known to grow on fibrin
      matrices, the role of this protein in trophoblast repair processes remains
      unclear. We hypothesize that fibrin may have an essential role in trophoblast
      remodeling. METHODS: Morphology and spreading of primary early-term human
      trophoblasts and villi explants were investigated on various fibrin components.
      Cross-linking of matrices was evaluated by D-dimer assay. TF procoaguant
      activity, protein and mRNA levels in cells and villi were determined by
      chromogenic assay, ELISA, immunohistochemistry and reverse-transcription PCR (RT
      PCR). RESULTS: Fibrin but not fibrinogen, thrombin or fibronectin caused
      increased trophoblast proliferation and spreading. Trophoblasts cultured on
      factor XIII (FXIII) depleted fibrin caused their increased proliferation and
      spreading, associated with cross-linking. FXIII addition further increased this
      effect, while cell culturing on active FXIII without fibrin retained cellular
      proliferation. Decreased TF activity, antigen and RNA expression were
      demonstrated in fibrin-cultured trophoblasts and villi explants, compared to
      matrigel explants. CONCLUSION: Results obtained demonstrate distinct mechanisms
      underlying fibrin cross-linking, which can affect trophoblast proliferation. The
      excess of fibrin deposits may be limited by the decrease in TF levels, thus
      enabling adequate placental perfusion. These findings demonstrate fibrin
      importance for placental repair and may partly explain poor pregnancy outcome
      associated with certain fibrinogen/fibrin abnormalities and FXIII deficiency.

PMID- 24041636
TI  - Aortic dissection can cause Takotsubo cardiomyopathy.

PMID- 24041637
TI  - Novel joint cupping clinical maneuver for ultrasonographic detection of knee
      joint effusions.
AB  - INTRODUCTION: Knee effusions occur due to traumatic and atraumatic causes.
      Clinical diagnosis currently relies on several provocative techniques to
      demonstrate knee joint effusions. Portable bedside ultrasonography (US) is
      becoming an adjunct to diagnosis of effusions. We hypothesized that a US approach
      with a clinical joint cupping maneuver increases sensitivity in identifying
      effusions as compared to US alone. METHODS: Using unembalmed cadaver knees, we
      injected fluid to create effusions up to 10 mL. Each effusion volume was measured
      in a lateral transverse location with respect to the patella. For each effusion
      we applied a joint cupping maneuver from an inferior approach, and re-measured
      the effusion. RESULTS: With increased volume of saline infusion, the mean depth
      of effusion on ultrasound imaging increased as well. Using a 2-mm cutoff, we
      visualized an effusion without the joint cupping maneuver at 2.5 mL and with the
      joint cupping technique at 1 mL. Mean effusion diameter increased on average 0.26
      cm for the joint cupping maneuver as compared to without the maneuver. The
      effusion depth was statistically different at 2.5 and 7.5 mL (P < .05).
      CONCLUSIONS: Utilizing a joint cupping technique in combination with US is a
      valuable tool in assessing knee effusions, especially those of subclinical
      levels. Effusion measurements are complicated by uneven distribution of effusion
      fluid. A clinical joint cupping maneuver concentrates the fluid in one recess of
      the joint, increasing the likelihood of fluid detection using US.

PMID- 24041638
TI  - Assisted head extension minimizes the frequency of dental contact with
      laryngoscopic blade during tracheal intubation.
AB  - OBJECTIVES: We hypothesized that the assisted maintenance of head extension would
      reduce the frequency of direct contact between the laryngoscope blade and the
      maxillary incisors during tracheal intubation. METHODS: Sixty-eight patients
      undergoing elective surgical procedures under general anesthesia were enrolled in
      this prospective, randomized, controlled crossover study. A single experienced
      anesthesiologist performed the simulated tracheal intubations with a classic
      Macintosh laryngoscope. After reaching the sniffing position during direct
      laryngoscopy, tracheal intubations with and without maintaining the head
      extension (by an assistant) were simulated twice in each patient in random order.
      The occurrence of dental contact with the laryngoscope blade was recorded during
      the simulated tracheal intubation. The distance between the laryngoscopic blade
      and maxillary central incisors was assessed using a digital caliper. The angle of
      head extension and the glottic view were also evaluated. RESULTS: The frequency
      of dental contact was lower with the assisted head extension than without it
      (25/68 [37%] vs 67/68 [99%], P < .001). The blade-to-tooth distance was longer
      with assistance than without it (1.8 +/- 1.9 [0-8] mm vs 0.0 +/- 0.1 [0-1] mm, P
      < .001). The angle of head extension was greater with assistance than without it
      (26.6 degrees  +/- 5.8 degrees  [6.0 degrees -37.4 degrees ] vs 19.9 degrees  +/-
      5.4 degrees  [3.4 degrees -31.8 degrees ], P < .001). No significant difference
      was observed between 2 simulated tracheal intubations with regard to the glottic
      views. CONCLUSION: The assisted maintenance of head extension during the
      simulation of tracheal intubation reduced the frequency of dental contact with
      the laryngoscopic blade without compromising the laryngoscopic views. The results
      of this study suggest that assisted head extension during tracheal intubation may
      reduce the possibility of unexpected dental injury.

PMID- 24041639
TI  - Refractory hypotension in Takotsubo cardiomyopathy: intuitive therapies could
      deteriorate hemodynamic stability.

PMID- 24041640
TI  - B-type natriuretic peptide and infarct size in non-ST-elevation myocardial
      infarction.

PMID- 24041641
TI  - Differences of postresuscitation myocardial dysfunction in ventricular
      fibrillation versus asphyxiation.
AB  - PURPOSE: This study aims to characterize postresuscitation myocardial dysfunction
      in 2 porcine models of cardiac arrest (CA): ventricular fibrillation cardiac
      arrest (VFCA) and asphyxiation cardiac arrest (ACA). METHODS: Thirty-two pigs
      were randomized into 2 groups. The VFCA group (n = 16) were subject to programed
      electrical stimulation, and the ACA group (n = 16) underwent endotracheal tube
      clamping to induce CA. Once induced, CA remained untreated for 8 minutes. Two
      minutes after initiation of cardiopulmonary resuscitation (CPR), defibrillation
      was attempted until return of spontaneous circulation (ROSC) was achieved or
      animals died. RESULTS: Return of spontaneous circulation was 100% successful in
      VFCA and 50% successful in ACA. Cardiopulmonary resuscitation duration in VFCA
      was about half as short as in ACA. The survival time of VFCA was significantly
      longer than that of ACA. Ventricular fibrillation cardiac arrest had better mean
      arterial pressure, cardiac output, and left ventricular +/- dp/dt(max) after ROSC
      than ACA. Echocardiography revealed significantly lower left ventricular ejection
      fraction in ACA than in VFCA. Myocardial perfusion imaging using single-photon
      emission computed tomography demonstrated that myocardial injuries after ACA were
      more severe and widespread than after VFCA. Under a transmission electron
      microscope, the overall heart morphologic structure and the mitochondrial crista
      structure were less severely injured in the VFCA group than in the ACA group.
      Moreover, the percentage of apoptotic cardiomyocytes was higher in ACA than in
      VFCA. CONCLUSIONS: Compared with VFCA, ACA causes more severe cardiac dysfunction
      associated with less successful resuscitation and shorter survival time.

PMID- 24041642
TI  - Atraumatic painless compartment syndrome.
AB  - Acute compartment syndrome is a time-sensitive diagnosis and surgical emergency
      because it poses a threat to life and the limbs. It is defined by Matsen et al
      (Surg Gynecol Obstet. 1978;147(6):943-949) as "a condition in which increased
      pressure within a limited space compromises the circulation and function of the
      tissues within that space." The most common cause of compartment syndrome is
      traumatic injury. A variety of other conditions such as vascular injuries,
      bleeding disorders, thrombosis, fasciitis, gas gangrene, rhabdomyolysis,
      prolonged limb compression, cellulitis, and nephrotic syndrome may also cause
      compartment syndrome. Patients who are elderly, have preexisting nerve damage, or
      have psychopathology may have an atypical presentation. This case highlights the
      first report of a 75-year-old woman who developed painless bilateral compartment
      syndrome in the absence of traumatic injury.

PMID- 24041643
TI  - Stove-related injuries treated in EDs in the United States, 1990-2010.
AB  - BACKGROUND: Household stoves are a common source of injury in the United States.
      PURPOSE: To investigate the epidemiology of stove-related injuries. METHODS: The
      National Electronic Injury Surveillance System database was used to analyze cases
      of nonfatal stove-related injuries treated in US hospital emergency departments
      (EDs) from 1990 through 2010. RESULTS: An estimated 910696 (95% CI, 789279
      1032113) individuals were treated for stove-related injuries during the 21-year
      study period, yielding an average of 43366 injured persons annually or 5 injuries
      every hour. The number (m = -252.85; P = .033) and rate (m = -0.026; P < .001) of
      injured individuals significantly decreased during the study. Injuries were
      highest in 1991 (50656 cases; 2.0 per 10000) and lowest in 2005 (38669 cases;
      1.31 per 10000), although there was an increase in 2010 (48990 cases; 1.58 per
      10000). Patients <=19 years experienced 41.3% of stove-related injuries. The
      primary mechanism of injury was contact with stove parts (37.5%). The body region
      most commonly injured was the hand (44.6%), and a thermal burn was the most
      common diagnosis (51.8%). The majority (94.4%) of patients were treated and
      released from the ED. Patients >60 years of age were 3.85 (95% CI, 2.97-4.98)
      times more likely to be admitted to the hospital than younger patients.
      CONCLUSIONS: This is the first comprehensive study of stove-related injuries in
      the United States using a nationally representative sample. Strategies to prevent
      stove-related injuries should address the multiple mechanisms of injury.

PMID- 24041644
TI  - Retromolar trigone squamous cell cancers: a reappraisal of 16 section MDCT for
      assessing mandibular invasion.
AB  - AIM: To reinvestigate the accuracy of 16 section multidetector computed
      tomography (MDCT) in assessing mandibular invasion in retromolar trigone (RMT)
      squamous cell cancers (SCC). MATERIALS AND METHODS: A search for diagnosed cases
      of early RMT SCC that were both imaged and treated at Tata Memorial Centre,
      Mumbai, India, between 2007 and 2010, was undertaken and yielded 37 patients. The
      average tumour size was 2.6 cm. All patients had undergone segmental, marginal,
      or hemimandibulectomy within 2 weeks of imaging. Imaging records archived on the
      picture archiving and communication system (PACS) were analysed. Contrast
      enhanced CT had been performed using a 16 section MDCT system using the puffed
      cheek technique. Image acquisition was at 2.5 mm section thickness, but axial
      images and isotropic coronal and sagittal multiplanar reformations were generated
      ad hoc from 0.625 mm retro-reconstructed images. Optimal oblique reformations
      were generated at will by the radiologist to depict the RMT in its entirety. The
      soft-tissue algorithm and bone window or bone algorithm reformations and axial
      images were analysed on a volume viewer integrated within the PACS using
      triangulation. Two investigators independently studied the images and these were
      compared with the findings at histopathology. RESULTS: The sensitivity,
      specificity, and accuracy of 16 section MDCT for mandibular cortical and marrow
      invasion was 94, 90, and 91.8% and 83, 92, and 89%, respectively. Use of ad hoc
      generated oblique reformation contributed to the enhanced sensitivity and
      specificity. The accuracy for inferior alveolar canal invasion was 100%. There
      was excellent agreement between the two observers. CONCLUSION: Sixteen-section
      MDCT used to its full potential has high accuracy for the detection of mandibular
      invasion in RMT SCC.

PMID- 24041645
TI  - Hydrogen-bonding changes of internal water molecules upon the actions of
      microbial rhodopsins studied by FTIR spectroscopy.
AB  - Microbial rhodopsins are classified into type-I rhodopsins, which utilize light
      energy to perform wide varieties of function, such as proton pumping, ion
      pumping, light sensing, cation channels, and so on. The crystal structures of
      several type-I rhodopsins were solved and the molecular mechanisms have been
      investigated based on the atomic structures. However, the crystal structures of
      proteins of interest are not always available and the basic architectures are
      sometimes quite similar, which obscures how the proteins achieve different
      functions. Stimulus-induced difference FTIR spectroscopy is a powerful tool to
      detect minute structural changes providing a clue for elucidating the molecular
      mechanisms. In this review, the studies on type-I rhodopsins from fungi and
      marine bacteria, whose crystal structures have not been solved yet, were
      summarized. Neurospora rhodopsin and Leptosphaeria rhodopsin found from Fungi
      have sequence similarity. The former has no proton pumping function, while the
      latter has. Proteorhodopsin is another example, whose proton pumping machinery is
      altered at alkaline and acidic conditions. We described how the structural
      changes of protein were different and how water molecules were involved in them.
      We reviewed the results on dynamics of the internal water molecules in pharaonis
      halorhodopsin as well. This article is part of a Special Issue entitled: Retinal
      Proteins - You can teach an old dog new tricks. 

PMID- 24041646
TI  - Relevance of rhodopsin studies for GPCR activation.
AB  - Rhodopsin, the dim-light photoreceptor present in the rod cells of the retina, is
      both a retinal-binding protein and a G protein-coupled receptor (GPCR). Due to
      this conjunction, it benefits from an arsenal of spectroscopy techniques that can
      be used for its characterization, while being a model system for the important
      family of Class A (also referred to as "rhodopsin-like") GPCRs. For instance,
      rhodopsin has been a crucial player in the field of GPCR structural biology.
      Until 2007, it was the only GPCR for which a high-resolution crystal structure
      was available, so all structure-activity analyses on GPCRs, from structure-based
      drug discovery to studies of structural changes upon activation, were based on
      rhodopsin. At present, about a third of currently available GPCR structures are
      still from rhodopsin. In this review, I show some examples of how these
      structures can still be used to gain insight into general aspects of GPCR
      activation. First, the analysis of the third intracellular loop in rhodopsin
      structures allows us to gain an understanding of the structural and dynamic
      properties of this region, which is absent (due to protein engineering or poor
      electron density) in most of the currently available GPCR structures. Second, a
      detailed analysis of the structure of the transmembrane domains in inactive,
      intermediate and active rhodopsin structures allows us to detect early
      conformational changes in the process of ligand-induced GPCR activation. Finally,
      the analysis of a conserved ligand-activated transmission switch in the
      transmembrane bundle of GPCRs in the context of the rhodopsin activation cycle,
      allows us to suggest that the structures of many of the currently available
      agonist-bound GPCRs may correspond to intermediate active states. While the focus
      in GPCR structural biology is inevitably moving away from rhodopsin, in other
      aspects rhodopsin is still at the forefront. For instance, the first studies of
      the structural basis of disease mutants in GPCRs, or the most detailed analysis
      of cellular GPCR signal transduction networks using a systems biology approach,
      have been carried out in rhodopsin. Finally, due again to its unique properties
      among GPCRs, rhodopsin will likely play an important role in the application of X
      ray free electron laser crystallography to time-resolved structural biology in
      membrane proteins. Rhodopsin, thus, still remains relevant as a model system to
      study the molecular mechanisms of GPCR activation. This article is part of a
      Special Issue entitled: Retinal Proteins-You can teach an old dog new tricks. 

PMID- 24041647
TI  - Diversity of animal opsin-based pigments and their optogenetic potential.
AB  - Most animal opsin-based pigments are typical G protein-coupled receptors (GPCR)
      and consist of a protein moiety, opsin, and 11-cis retinal as a chromophore. More
      than several thousand opsins have been identified from a wide variety of animals,
      which have multiple opsin genes. Accumulated evidence reveals the molecular
      property of opsin-based pigments, particularly non-conventional visual pigments
      including non-visual pigments. Opsin-based pigments are generally a bistable
      pigment having two stable and photointerconvertible states and therefore are
      bleach-resistant and reusable, unlike vertebrate visual pigments which become
      bleached. The opsin family contains Gt-coupled, Gq-coupled, Go-coupled, Gs
      coupled, Gi-coupled, and Gi/Go-coupled opsins, indicating the existence of a
      large diversity of light-driven GPCR-signaling cascades. It is suggested that
      these molecular properties might contribute to different physiologies. In
      addition, various opsin based-pigments, especially nonconventional visual
      pigments having different molecular characteristics would facilitate the design
      and development of promising optogenetic tools for modulating GPCR-signaling,
      which is involved in a wide variety of physiological responses. We here introduce
      molecular and functional properties of various kinds of opsins and discuss their
      physiological function and also their potentials for optogenetic applications.
      This article is part of a Special Issue entitled: Retinal proteins - you can
      teach an old dog new tricks. 

PMID- 24041648
TI  - Contributions of the S2 spike ectodomain to attachment and host range of
      infectious bronchitis virus.
AB  - The spike protein is the major viral attachment protein of the avian coronavirus
      infectious bronchitis virus (IBV) and ultimately determines viral tropism. The S1
      subunit of the spike is assumed to be required for virus attachment. However, we
      have previously shown that this domain of the embryo- and cell culture adapted
      Beaudette strain, in contrast to that of the virulent M41 strain, is not
      sufficient for binding to chicken trachea (Wickramasinghe et al., 2011). In the
      present study, we demonstrated that the lack of binding of Beaudette S1 was not
      due to absence of virus receptors on this tissue nor due to the production of S1
      from mammalian cells, as S1 proteins expressed from chicken cells also lacked the
      ability to bind IBV-susceptible embryonic tissue. Subsequently, we addressed the
      contribution of the S2 subunit of the spike in IBV attachment. Recombinant IBV
      Beaudette spike ectodomains, comprising the entire S1 domain and the S2
      ectodomain, were expressed and analyzed for binding to susceptible embryonic
      chorio-allantoic membrane (CAM) in our previously developed spike histochemistry
      assay. We observed that extension of the S1 domain with the S2 subunit of the
      Beaudette spike was sufficient to gain binding to CAM. A previously suggested
      heparin sulfate binding site in Beaudette S2 was not required for the observed
      binding to CAM, while sialic acids on the host tissues were essential for the
      attachment. To further elucidate the role of S2 the spike ectodomains of virulent
      IBV M41 and chimeras of M41 and Beaudette were analyzed for their binding to CAM,
      chicken trachea and mammalian cell lines. While the M41 spike ectodomain showed
      increased attachment to both CAM and chicken trachea, no binding to mammalian
      cells was observed. In contrast, Beaudette spike ectodomain had relatively weak
      ability to bind to chicken trachea, but displayed marked extended host range to
      mammalian cells. Binding patterns of chimeric spike ectodomains to these tissues
      and cells indicate that S2 subunits most likely do not contain an additional
      independent receptor-binding site. Rather, the interplay between S1 and S2
      subunits of spikes from the same viral origin might finally determine the avidity
      and specificity of virus attachment and thus viral host range.

PMID- 24041649
TI  - Secular trends in echocardiographic left ventricular mass in the community: the
      Framingham Heart Study.
AB  - OBJECTIVE: To investigate secular trends in echocardiographically determined left
      ventricular mass (LVM). DESIGN, SETTING AND PARTICIPANTS: Longitudinal community
      based cohort study in Framingham, Massachussetts. LVM was calculated from routine
      echocardiography in 4320 participants (52% women) of the Framingham offspring
      cohort at examination cycles 4 (1987-1991), 5 (1991-1995), 6 (1995-1998) and 8
      (2005-2008), totalling 13 971 person-observations. MAIN OUTCOME MEASURES: Sex
      specific trends in mean LVM (and its components, LV diastolic diameter (LVDD) and
      LV wall thickness (LVWT)), and LVM indexed to body surface area (BSA). RESULTS:
      In men, age-adjusted LVM modestly increased from examination 4 to 8 (192 g to 198
      g, p-trend=0.0005), whereas, in women it decreased from 147 g at examination 4 to
      140 g at examination 8 (p-trend<0.0001). The trend for increasing LVM in men
      tracked with an increasing LVDD (p-trend=0.0002), whereas the decline in LVM in
      women was accompanied by a decrease in LVWT (p-trend<0.0001). Indexing LVM to BSA
      abolished the increasing trend in men (p-trend=0.49), whereas, the decreasing
      trend in women was maintained. CONCLUSIONS: In our longitudinal analysis of a
      large community-based sample spanning two decades, we observed sex-related
      differences in trends in LVM, with a modest increase of LVM in men (likely
      attributable to increasing body size), but a decrease in women. Additional
      studies are warranted to elucidate the basis for these sex-related differences.

PMID- 24041650
TI  - Niacin--a case study for the role of event-driven versus surrogate endpoint
      trials.

PMID- 24041651
TI  - Tumour necrosis factor-alpha is a foe for patients with acute myocardial
      infarction.

PMID- 24041652
TI  - Knockdown of thioredoxin-interacting protein ameliorates high glucose-induced
      epithelial to mesenchymal transition in renal tubular epithelial cells.
AB  - Epithelial to mesenchymal transition (EMT) of tubular cells contributes to the
      renal accumulation of matrix protein that is associated with diabetic
      nephropathy. Both high glucose and transforming growth factor-beta (TGF-beta) are
      able to induce EMT in cell culture. In this study, we examined the role of the
      thioredoxin-interacting protein (TXNIP) on EMT induced by high glucose or TGF
      beta1 in HK-2 cells. EMT was assessed by the expression of alpha-smooth muscle
      actin (alpha-SMA) and E-cadherin and the induction of a myofibroblastic
      phenotype. High glucose (30mM) was shown to induce EMT at 72h. This was blocked
      by knockdown of TXNIP or antioxidant NAC. Meanwhile, we also found that knockdown
      of TXNIP or antioxidant NAC inhibited high glucose-induced generation of reactive
      oxygen species (ROS), phosphorylation of p38 MAPK and ERK1/2 and expression of
      TGF-beta1. HK-2 cells that were exposed to TGF-beta1 (4ng/ml) also underwent EMT.
      The expression of TXNIP gene and protein was increased in HK-2 cells treated with
      TGF-beta1. Transfection with TXNIP shRNA was able to attenuate TGF-beta1 induced
      EMT. These results suggested that knockdown of TXNIP antagonized high glucose
      induced EMT by inhibiting ROS production, activation of p38 MAPK and ERK1/2, and
      expression of TGF-beta1, highlighting TXNIP as a potential therapy target for
      diabetic nephropathy. 

PMID- 24041653
TI  - Distinctive microRNA signature associated of neoplasms with the Wnt/beta-catenin
      signaling pathway.
AB  - As the crucial biological regulators, microRNAs that act by suppressing their
      target genes are involved in a variety of pathophysiological processes. It is
      generally accepted that microRNAs are often dysregulated in many types of
      neoplasm and other human diseases. In neoplasm, microRNAs may function as
      oncogenes or tumor suppressors. As constitutive activation of the Wnt signaling
      pathway is a common feature of neoplasm and contributes to its development,
      progression and metastasis in various cancers, numerous studies have revealed
      that microRNA-mediated gene regulation are interconnected with the Wnt/beta
      catenin signaling pathway, forming a Wnt/beta-catenin-microRNA regulatory
      network, which is critical to successful targeting of the Wnt/beta-catenin
      pathway for oncotherapy. In this review, we aim to accumulate recent advances on
      microRNAs that work in tandem with Wnt/beta-catenin signaling in tumorigenesis,
      with particular focus on how microRNAs affect Wnt/beta-catenin activity as well
      as how microRNAs are regulated through the Wnt/beta-catenin pathway. 

PMID- 24041655
TI  - Notch activation augments nitric oxide/soluble guanylyl cyclase signaling in
      immortalized ovarian surface epithelial cells and ovarian cancer cells.
AB  - Nitric oxide (NO) is generated by tumor, stromal and endothelial cells and plays
      a multifaceted role in tumor biology. Many physiological functions of NO are
      mediated by soluble guanylyl cyclase (sGC) and NO/sGC signaling has been shown to
      promote proliferation and survival of ovarian cancer cells. However, how NO/sGC
      signaling is modulated in ovarian cancer cells has not been studied. The
      evolutionarily conserved Notch signaling pathway plays an oncogenic role in
      ovarian cancer. Here, we report that all three ovarian cancer cell lines we
      examined express a higher level of GUCY1B3 (the beta subunit of sGC) compared to
      non-cancerous immortalized ovarian surface epithelial (IOSE) cell lines.
      Interestingly, the highest expression of GUCY1B3 in ovarian cancer OVCAR3 cells
      is concurrent with the expression of Notch3. In IOSE cells, forced activation of
      Notch3 increases the expression of GUCY1B3, NO-induced cGMP production, and the
      expression of cGMP-dependent protein kinase (PKG), thereby enhancing NO- and cGMP
      induced phosphorylation of vasodilator-stimulated phosphoprotein (VASP, a direct
      PKG substrate protein). In contrast, inhibition of Notch by DAPT reduces GUCY1B3
      expression and NO-induced cGMP production and VASP phosphorylation in OVCAR3
      cells. Finally, we confirmed that inhibition of sGC by ODQ decreases growth of
      ovarian cancer cells. Together, our work demonstrates that Notch is a positive
      regulator of NO/sGC signaling in IOSE and ovarian cancer cells, providing the
      first evidence that Notch and NO signaling pathways interact in IOSE and ovarian
      cancer cells. 

PMID- 24041654
TI  - Reversible inhibitors of regulators of G-protein signaling identified in a high
      throughput cell-based calcium signaling assay.
AB  - Regulator of G-protein signaling (RGS) proteins potently suppress G-protein
      coupled receptor (GPCR) signal transduction by accelerating GTP hydrolysis on
      activated heterotrimeric G-protein alpha subunits. RGS4 is enriched in the CNS
      and is proposed as a therapeutic target for treatment of neuropathological states
      including epilepsy and Parkinson's disease. Therefore, identification of novel
      RGS4 inhibitors is of interest. An HEK293-FlpIn cell-line stably expressing M3
      muscarinic receptor with doxycycline-regulated RGS4 expression was employed to
      identify compounds that inhibit RGS4-mediated suppression of M3-muscarinic
      receptor signaling. Over 300,000 compounds were screened for an ability to
      enhance Galphaq-mediated calcium signaling in the presence of RGS4. Compounds
      that modulated the calcium response in a counter-screen in the absence of RGS4
      were not pursued. Of the 1365 RGS4-dependent primary screen hits, thirteen
      compounds directly target the RGS-G-protein interaction in purified systems. All
      thirteen compounds lose activity against an RGS4 mutant lacking cysteines,
      indicating that covalent modification of free thiol groups on RGS4 is a common
      mechanism. Four compounds produce >85% inhibition of RGS4-G-protein binding at
      100MUM, yet are >50% reversible within a ten-minute time frame. The four
      reversible compounds significantly alter the thermal melting temperature of RGS4,
      but not G-protein, indicating that inhibition is occurring through interaction
      with the RGS protein. The HEK cell-line employed for this study provides a
      powerful tool for efficiently identifying RGS-specific modulators within the
      context of a GPCR signaling pathway. As a result, several new reversible, cell
      active RGS4 inhibitors have been identified for use in future biological studies.

PMID- 24041656
TI  - Acetylcholine-metabolizing butyrylcholinesterase (BCHE) copy number and single
      nucleotide polymorphisms and their role in attention-deficit/hyperactivity
      syndrome.
AB  - A previous genome-wide screen for copy number variations (CNVs) in attention
      deficit/hyperactivity disorder (ADHD) revealed a de novo chromosome 3q26.1
      deletion in one of the patients. Candidate genes at this locus include the
      acetylcholine-metabolizing butyrylcholinesterase (BCHE) expressing gene (OMIM
      #177400), which is of particular interest. The present study investigates the
      hypothesis that the heterozygous deletion of the BCHE gene is associated with
      adult ADHD (aADHD). Ina first step, we screened 348 aADHD patients and 352
      controls for stretches of loss of heterozygosity (LOH) across the entire BCHE
      gene to screen for the deletion. Our second aim was to clarify whether BCHE
      single nucleotide polymorphisms (SNPs) themselves influence the risk towards
      ADHD. Putative functional consequences of associated SNPs as well as their un
      typed proxies were predicted by several bioinformatic tools. 96 individuals
      displayed entirely homozygous genotype reads in all 12 examined SNPs, making them
      possible candidates to harbor a heterozygous BCHE deletion. DNA from these 96
      probands was further analyzed by real-time PCR using a BCHE-specific CNV assay.
      However, no deletion was found. Of the 12 tag SNPs that passed inclusion
      criteria, rs4680612 and rs829508 were significantly associated with aADHD, as
      their minor alleles occurred more often in cases than in controls (p = 0.018 and
      p = 0.039, respectively). The risk variant rs4680612 is located in the
      transcriptional control region of the gene and predicted to disrupt a binding
      site for MYT-1, which has previously been associated with mental disorders.
      However, when examining a second independent adult ADHD sample of 353 cases, the
      association did not replicate. When looking up the deletion in three genome-wide
      screens for CNV in ADHD and combining it with the present study, it became
      apparent that 3 from a total of 1030 ADHD patients, but none of 5787 controls,
      featured a deletion of the BCHE promoter region including rs4680612 (p =
      0.00004). Taken together, there are several lines of evidence suggesting a
      potential involvement of BCHE in the etiopathology of ADHD, as a rare hemizygous
      deletion as well as a common SNP in the same region are associated with disease,
      although with different penetrance. Both variations result in the disruption of
      the binding site of the transcription factor MYT-1 suggesting epistatic effects
      of BCHE and MYT-1 in the pathogenesis of ADHD. As we were not able to replicate
      the SNP association, our findings should be considered preliminary and call for
      larger studies in extended phenotypes.

PMID- 24041657
TI  - A rapid and highly sensitive UPLC-MS/MS method using pre-column derivatization
      with 2-picolylamine for intravenous and percutaneous pharmacokinetics of valproic
      acid in rats.
AB  - A rapid, highly sensitive and specific ultra-performance liquid chromatography
      coupled to tandem mass spectrometry (UPLC-MS/MS) for the detection of valproic
      acid (VPA) in rat plasma following the topical application was developed and
      validated. This method was carried out with pre-column derivatization using 2
      picolylamine (PA) which reacts with the carboxylic acid group of VPA. The
      derivatization was completed in 10min and the resulting PA-VPA derivative enabled
      the sensitive detection of VPA in selected reaction monitoring (SRM) mode. Sample
      preparation was done with simple liquid-liquid extraction and chromatographic
      separation was achieved within 5min on a C18 column using a gradient elution with
      the mobile phase of 2mM ammonium formate containing 0.1% formic acid and
      methanol. The standard curves were linear over the concentration range of 0.07
      200MUg/mL with a correlation coefficient higher than 0.99. The limit of detection
      (LOD) and the lower limit of quantification (LLOQ) was 0.03 and 0.07MUg/mL,
      respectively with 100MUL of plasma sample. The intra- and inter-day precisions
      were measured to be below 10.7% and accuracies were within the range of 94.1
      115.9%. The validated method was successfully applied to the pharmacokinetics of
      VPA in the rat following topical and intravenous applications. 

PMID- 24041658
TI  - Corneal imaging of intrastromal femtosecond laser treatment for presbyopia
      (Intracor((r))).
AB  - PURPOSE: To evaluate anatomic appearance and corneal cellular modifications after
      monocular Intracor((r)) procedure with two different anterior segment imaging
      techniques within the first postoperative year. PATIENTS AND METHODS: Four
      patients underwent an Intracor((r)) procedure in one eye performed at Clinique de
      la vision, and corneal imaging was performed in Quinze-Vingts National
      Ophthalmology Hospital. Slit-lamp photography, confocal microscopy with
      Heidelberg retinal tomography (HRT) and anterior segment spectral-domain optical
      coherence tomography (OCT) were performed 2 days, and 1, 6, and 12 months after
      the procedure. RESULTS: Confocal microscopy showed strong cellular activation of
      keratocytes within the first postoperative month which diminished over time. The
      linear femtosecond incisions appeared as hyper-reflective regular lines and
      reflectivity decreased throughout the follow-up period. After 6 months, a
      fibrotic process with appearance of corneal scars was visible as small
      intrastromal hyper-reflective lines and thick hyper-reflective spicules around
      the incisions and remained stable over time. On spectral-domain OCT, the size and
      depth of the incisions decreased from the center to the periphery. Visibility of
      the corneal femtosecond incisions on OCT decreased from day 2 until they almost
      disappeared at 12 months. The incision angles seemed to curve progressively from
      the center to the periphery in their deep portion on the peripheral rings.
      CONCLUSION: Corneal cellular modifications found on HRT, anatomical features, and
      the sizes of the intrastromal rings, may provide valuable information on this new
      refractive technique.

PMID- 24041659
TI  - [Filamentous hypopyon uveitis: unilateral fungal iris abscesses in an HIV
      infected drug abuser].

PMID- 24041660
TI  - [Late enophthalmos secondary to silent sinus syndrome after orbital
      decompression].

PMID- 24041661
TI  - Nanogold/mesoporous carbon foam-mediated silver enhancement for graphene-enhanced
      electrochemical immunosensing of carcinoembryonic antigen.
AB  - Nanogold functionalized mesoporous carbon foam (Au/MCF) coupling with a signal
      amplification by C-Au synergistic silver enhancement was designed for sensitive
      electrochemical immunosensing of biomarker. The Au/MCF was prepared by in situ
      growth of nanogold on carboxylated MCF and used as a tracing tag to label signal
      antibody via the inherent interaction between protein and nanogold. The
      immunosensor was prepared by covalently immobilizing capture antibody on an
      electrochemically reduced graphene oxide/chitosan film modified glassy carbon
      electrode. Through a sandwich-type immunoreaction, Au/MCF tags were captured on
      the immunoconjugates to induce a silver deposition process. The electrochemical
      stripping signal of the deposited silver was used to monitor the immunoreaction.
      The Au/MCF-mediated silver enhancement along with the graphene-promoted electron
      transfer led to high detection sensitivity of carcinoembryonic antigen. Under
      optimal conditions, the proposed immunoassay method showed wide linear range from
      0.05 pg mL(-1) to 1 ng mL(-1) and a detection limit down to 0.024 pg mL(-1). The
      newly designed amplification strategy holds great potential for ultrasensitive
      electrochemical biosensing of other analytes.

PMID- 24041662
TI  - Core-shell hybrid nanomaterial based on prussian blue and surface active
      maghemite nanoparticles as stable electrocatalyst.
AB  - A novel core-shell nanomaterial based on prussian blue (PB) coating on peculiar
      surface active maghemite nanoparticles (SAMNs), was developed. The synthetic
      process involves the direct crystallization of Fe(II)(CN)6(4-) onto the surface
      of SAMNs by simple incubation in water at controlled pH, demonstrating the
      presence of under-coordinated Fe(III) on nanoparticle surface. The coating
      reaction occurs in a narrow pH range and the synthetic procedure was optimized.
      The resulting SAMN@PB hybrid nanostructures were characterized by transmission
      and scanning electron microscopy, Mossbauer, UV-vis and FTIR spectroscopy and X
      ray powder diffraction. The nanomaterial, characterized by high stability in
      alkaline media, behave as excellent electro-catalyst for hydrogen peroxide
      reduction. The stability of SAMN@PB hybrid has been investigated as a function of
      pH, showing excellent stability up to pH 9.0 and demonstrating the feasibility of
      SAMNs, superficially derivatized with prussian blue, to produce an efficient and
      extremely stable nanostructured material. This maghemite supported nanostructured
      prussian blue was applied to develop a sensor, based on a simple carbon paste
      electrode, which was able to catalyze the electro-reduction of hydrogen peroxide,
      in aqueous solutions, buffered at pH 7.0, at low applied potentials (0.0 V vs.
      SCE).

PMID- 24041663
TI  - Amperometric biosensing of organophosphate and organocarbamate pesticides
      utilizing polypyrrole entrapped acetylcholinesterase electrode.
AB  - The work presented here describes a novel, easy and low-cost method of
      fabrication of a highly sensitive acetylcholinesterase biosensor and its
      application to detect organophosphate and organocarbamate pesticides.
      Acetylcholinesterase was electro-immobilized into a thick conducting layer of
      polypyrrole. Porcine skin gelatin and gluteraldehyde mixture was used for
      stabilizing the system. Acetylthiocholine chloride was used as the substrate.
      Polypyrrole catalyzed the electrochemical oxidation of thiocholine and promoted
      the electron transfer, thus lowering the oxidation potential and increasing the
      detection sensitivity. Electro oxidation of thiocholine in polypyrrole matrix
      occurred at 0.1 V under low potential scan rate. The thiocholine sensitivity of
      the electrode was found to be 143 mA/M. The sensor was applied to detect the
      sample organophosphate pesticide ethylparaoxon and organocarbamate pesticide
      carbofuran. The detection limit for paraoxon was found to be 1.1 ppb and that for
      carbofuran is 0.12 ppb. The sensor showed good intra and inter state precision
      with relative standard deviation (RSD) 0.742% and 6.56% respectively. Both dry
      and wet storage stability were studied. The sensor stored at 0 degrees C in dry
      condition had a good storage stability retaining 70% of its original activity for
      4 months. During wet storage, the activity decrease followed the same trend,
      however, the operational stability at the end of the storage period was found to
      be less compared to the dry storage case. The developed biosensor is as a
      promising new tool for analysis of cholinesterase inhibitors.

PMID- 24041664
TI  - [A rare tumor of the median nerve in a young child: Intraneural perineurioma.
      About one clinical case].
AB  - Intraneural perineurioma is a rare benign peripheral sheath tumor, which is most
      prevalent in adolescents and young adults. It is characterized by focal
      perineural cell proliferation infiltrating the endoneurium leading to the
      macroscopic aspect of hypertrophic nerve. It typically presents a loss of motor
      function in the involved nerve. We report the case of a 3-year-old boy presented
      with painless, subcutaneous mass on the palmar aspect of his right hand without
      loss of motor function. Imaging studies showed a large mass within the median
      nerve suggesting schwannoma. Surgical exploration was undertaken. The tumor could
      not be removed without leading to motor and sensitive loss. Neurolysis of the
      hypertrophic fascicles was performed. Microbiopsies ruled out malignant tumor and
      could make the diagnosis of intraneural perineurioma of the median nerve. An
      annual clinical follow-up has been decided in order to detect any functional
      trouble such as loss of motor function. 

PMID- 24041665
TI  - [Forehead and temple aesthetic reconstruction].
AB  - The purpose of this article is to address the techniques of reconstruction of the
      forehead and the temple trying to add an "aesthetic" dimension, as the fourth
      dimension introduced by Burget for the reconstructive surgery of the nose.
      Achieve "aesthetic" reconstruction is to have constant attention to details. This
      is how to choose the right indication depending on the age and the etiology of
      the defect. This is to place incisions to perfection. And it is to be humble and
      open oneself to criticism, always seeking to improve the quality of its results. 

PMID- 24041666
TI  - Temporal expectation and spectral expectation operate in distinct fashion on
      neuronal populations.
AB  - The formation of temporal expectation (i.e., the prediction of "when") is of
      prime importance to sensory processing. It can modulate sensory processing at
      early processing stages probably via the entrainment of low-frequency neuronal
      oscillations in the brain. However, sensory predictions involve not only temporal
      expectation but also spectral expectation (i.e., the prediction of "what"). Here
      we investigated how temporal expectation may interrelate with spectral
      expectation by explicitly setting up temporal expectation and spectral
      expectation in a target detection task. We found that reaction time (RT) was
      shorter when targets were temporally expected than when they were temporally
      unexpected. The temporal expectation effect was larger with than without spectral
      expectation. However, this interaction in the behavioural data did not result
      from an interaction in the electroencephalography (EEG), where we observed
      independent main effects of temporal expectation and spectral expectation. More
      precisely, we found that the N1 and P2 event-related potential (ERP) components
      and the entrainment of low-frequency neuronal oscillations were exclusively
      modulated by temporal expectation, whilst only the P3 ERP component was modulated
      by spectral expectation. Our results, thus, support the idea that temporal
      expectation and spectral expectation operate in distinct fashion on neuronal
      populations. 

PMID- 24041667
TI  - The nature of anterograde and retrograde memory impairment after damage to the
      medial temporal lobe.
AB  - The study of anterograde and retrograde amnesia (AA and RA) in the laboratory and
      the clinic has provided important information about the structure and
      organization of memory. The severity of AA is usually correlated with the
      severity of RA. Nevertheless, variations in the expression of AA and RA have been
      reported, which presumably reflect variation in the locus and extent of brain
      damage. The relationship between AA and RA has rarely been described
      quantitatively in groups of patients where detailed anatomical information is
      available. We have quantified the severity of AA and RA for factual information
      in 11 memory-impaired patients with bilateral medial temporal lobe lesions,
      including 5 for whom detailed post-mortem neurohistological information was
      available. The findings describe an orderly relationship between AA and RA, such
      that patients with more severe AA also had more extensive RA. In addition, RA was
      measurable only after AA reached a substantial level of severity. This
      relationship between AA and RA in patients with identified medial temporal lobe
      lesions appears to describe a general principle, which applies to a range of
      etiologies, including traumatic amnesia, where the locus and extent of brain
      damage is less well understood. Whenever patients deviate substantially from the
      relationship described here, one should be alert to the likelihood that
      significant damage has occurred outside or in addition to the structures in the
      medial temporal lobe. 

PMID- 24041668
TI  - Early visual ERP sensitivity to the species and animacy of faces.
AB  - Assessing the agency of potential actors in the visual world is a critically
      important aspect of social cognition. Adult observers are generally capable of
      distinguishing real faces from artificial faces (even allowing for recent
      advances in graphics technology and motion capture); even small deviations from
      real facial appearance can lead to profound effects on face recognition.
      Presently, we examined how early components of visual event-related potentials
      (ERPs) are affected by the "life" in human faces and animal faces. We presented
      participants with real and artificial faces of humans and dogs, and analyzed the
      response properties of the P100 and the N170 as a function of stimulus appearance
      and task (species categorization vs. animacy categorization). The P100 exhibited
      sensitivity to face species and animacy. We found that the N170's differential
      responses to human faces vs. dog faces depended on the task participants'
      performed. Also, the effect of species was only evident for real faces of humans
      and dogs, failing to obtain with artificial faces. These results suggest that
      face animacy does modulate early components of visual ERPs-the N170 is not merely
      a crude face detector, but reflects the tuning of the visual system to natural
      face appearance. 

PMID- 24041669
TI  - Single pulse TMS differentially modulates reward behavior.
AB  - Greater knowledge of cortical brain regions in reward processing may set the
      stage for using transcranial magnetic stimulation (TMS) as a treatment in
      patients with avolition, apathy or other drive-related symptoms. This study
      examined the effects of single pulse (sp) TMS to two reward circuit targets on
      drive in healthy subjects. Fifteen healthy subjects performed the monetary
      incentive delay task (MID) while receiving fMRI-guided spTMS to either inferior
      parietal lobe (IPL) or supplemental motor area (SMA). The study demonstrated
      decreasing reaction times (RT) for increasing reward. It also showed significant
      differences in RT modulation for TMS pulses to the IPL versus the SMA. TMS pulses
      during the delay period produced significantly more RT slowing when targeting the
      IPL than those to the SMA. This RT slowing carried over into subsequent trials
      without TMS stimulation, with significantly slower RTs in sessions that had
      targeted the IPL compared to those targeting SMA. The results of this study
      suggest that both SMA and IPL are involved in reward processing, with opposite
      effects on RT in response to TMS stimulation. TMS to these target cortical
      regions may be useful in modulating reward circuit deficits in psychiatric
      populations. 

PMID- 24041670
TI  - Cushing's disease in 2012.
AB  - The aim of this study was to review the literature published and the most
      important papers presented to meetings on Cushing's disease from October 2011 to
      September 2012. The selection has been performed according to the authors'
      criteria. Articles have been classified into five groups: quality of life and
      perception of the disease, clinical features and pathophysiology, comorbidity
      conditions, diagnosis, and treatment. The results and conclusions of each
      publication are discussed. 

PMID- 24041671
TI  - [Clinical practice guideline for the diagnosis and treatment of pituitary
      apoplexy].
AB  - Classic pituitary apoplexy (PA) is an acute, life-threatening clinical syndrome
      caused by acute hemorrhage and/or infarction of the pituitary gland. PA is
      considered a neuroendocrinological emergency. However, there is no consensus
      about the best options for PA diagnosis and management. OBJECTIVE: To develop a
      clinical practice guideline with a number of recommendations for diagnosis and
      treatment of patients with PA based on the medical evidence available, in order
      to help clinicians involved in their care. METHODS: The clinical guideline for
      diagnosis and treatment of pituitary apoplexy issued in 2006 by the
      Neuroendocrinology Working Group of the Spanish Society of Endocrinology and
      Nutrition (SEEN) and the British Clinical Practice Guideline published in 2011
      were taken as the basis. The text has been adapted to the format used in most
      international medical journals. For this, after updated medical literature, the
      quality of evidence and the strength of the recommendations were evaluated using
      the system proposed by the Agency for Health Care Policy and Research (AHCPR).
      CONCLUSIONS: Diagnosis of pituitary apoplexy should be considered in all patients
      with acute severe headache with or without neuro-ophthalmic signs. Patients with
      PA must undergo a complete history and physical examination. All patients with
      suspected pituitary apoplexy should have urgent blood samples drawn to test
      electrolytes, renal function, liver function, coagulation screen, complete blood
      count, and basal levels of pituitary and peripheral hormones, and to rule out
      adrenocorticotropic hormone (ACTH) deficiency. Formal visual field assessment
      should be performed when the patient is clinically stable. Magnetic resonance
      imaging (MRI) is the imaging test of choice to confirm diagnosis. Indications for
      empirical urgent corticosteroid therapy in patients with PA include hemodynamic
      instability, impaired consciousness, reduced visual acuity, and severe visual
      field defects. In patients with these severe neuro-ophthalmic signs, surgery
      should be considered. Surgery should preferably be performed within seven days of
      the onset of symptoms. Patients with mild and stable signs may be managed
      conservatively with careful monitoring. Treatment and long-term follow-up of
      patients with PA should be conducted by a multidisciplinary team consisting,
      amongst others, of an experienced pituitary neurosurgeon, an ophthalmologist, and
      an endocrinologist.

PMID- 24041672
TI  - Different effects of three interferons L on Toll-like receptor-related gene
      expression in HepG2 cells.
AB  - IFNL1 (IL29), IFNL2 (IL28A) and IFNL3 (IL28B) might play important roles in anti
      viral defense. IFNL3 genotypes have been shown to be associated with hepatitis C
      spontaneous and treatment-induced viral clearance. The effects of IFNL1, IFNL2
      and IFNL3 on innate immunity including Toll-like receptor (TLR)-related pathway
      in human hepatocytes were examined. After G418 screening, we established the
      human hepatoma stable cell lines HepG2-IL28A, HepG2-IL28B, and HepG2-IL29,
      expressing IFNL2, IFNL3, and IFNL1 in conditioned medium, respectively, and a
      control cell line, HepG2-pcDNA3.1. We performed real-time RT-PCR to investigate
      84 Toll-like receptor-related gene expressions in triplicate and, using ddCt
      methods, compared these gene expressions in each cell line. IFNL2, IFNL3 and
      IFNL1 were respectively detected by ELISA in HepG2-IL28A, HepG2-IL28B and HepG2
      IL29. Compared to HepG2-pcDNA3.1 cells, 17 (20.2%), 11 (13.0%) and 16 genes
      (19.0%) were up-regulated 1.5-fold or more (p<0.05); 10 (11.9%), 2 (2.3%) and 10
      genes (11.9%) were 1.5-fold or more down-regulated (p<0.05) in HepG2-IL28A, HepG2
      IL28B and HepG2-IL29, respectively. EIF2AK2 and SARM1 were up-regulated among all
      cells. Of interest, TLR3, TLR4 and related molecules CXCL10 (IP10), IL6, EIF2K2,
      IFNB1, and IRF1, important genes in the progression of HCV-related pathogenesis
      and antiviral activities against HCV, in HepG2-IL28B, presented different
      profiles from those of HepG2-IL28A and HepG2-IL29. IFNL3 induces interferon
      stimulated genes (ISGs) that are reportedly associated with the progression of
      HCV-related pathogenesis and antiviral activities against HCV. IFNL is a powerful
      modulator of innate immune response and it is supposed that the 3 IFNLs may play
      different roles in the antiviral activity against HBV and HCV. 

PMID- 24041673
TI  - Evidence-based medicine and its application in clinical preimplantation
      embryology.
AB  - The randomized clinical trial (RCT) was developed to assess the efficacy of
      medical interventions by comparing a treatment group with a control group that
      did not receive treatment or received placebo. It has been evident that this
      study design is more suited to evaluation of drugs and less to complex
      interventions such as surgical procedures. The same can be said about assisted
      reproduction technology, which clearly belongs in the complex category. Yet,
      there have been no specific guidelines for the design of RCT in clinical
      embryology. Moreover, the reliability of the published data from arbitrarily
      designed trials has not been debated. The near absence of allocation concealment
      and blinding and the difficulties inherent in randomizing oocytes and embryos in
      addition to patients require further consideration. This work evaluates
      systematic reviews to assess the efficacy of interventions, including the use of
      different culture media, culture under reduced oxygen tension, blastocyst
      culture, co-culture with somatic cells, assisted hatching, preimplantation
      genetic screening and intracytoplasmic morphologically selected sperm injection.
      The overall quality of a RCT and the appropriate application of new technologies
      in clinical embryology may be improved if a specific set of guidelines were to be
      developed for such investigations.

PMID- 24041674
TI  - The reliability of VCUG performed within 24 hours after injection of
      dextranomer/hyaluronic acid in patients with vesico-ureteral reflux.
AB  - OBJECTIVE: To assess the reliability and negative predictive value of voiding
      cystourethrogram (VCUG) performed within 24 hours postoperatively. METHODS: Forty
      patients (56 ureters) who underwent first injection of dextranomer/hyaluronic
      acid (Dx/HA) because of vesicoureteral reflux (VUR) were enrolled. Patients with
      previous reflux operation or neurogenic disorders were excluded. All patients
      underwent the hydrodistention implantation technique (HIT). Patients underwent
      VCUG within 24 hours postoperatively and after 6 months. Grade 0 and grade 1 were
      considered to be cured. Negative predictive values of VCUG performed within 24
      hours postoperatively were assessed. RESULTS: The mean age of the patient was 98
      +/- 45.8 months. Twenty-seven patients were male and 13 patients were female. The
      number of refluxing ureters was 4, 12, 14, 12, and 14 in ascending order of VUR
      grade. Overall success rate of single injection therapy was 66.07%. Only 2
      ureters with grade IV and 1 patient with grade V VUR showed failure on 24-hour
      VCUG. The success rates on 6 months VCUG were 100%, 83.3%, 78.57%, 50%, and
      42.85% according to ascending order of VUR grade.The negative predictive value of
      24-hour VCUG were 100%, 83.3%, 78.57%, 60.0%, and 46.15% according to ascending
      order of VUR grade. VUR grade was the only factor associated with the
      discrepancy. Positive but weak correlation was noted between the preoperative
      grade of VUR and the rate of discrepancy on Spearman correlation analysis
      (Spearman correlation coefficient = 0.303, P value = .018). CONCLUSION: Twenty
      four hour VCUG cannot replace follow-up VCUG usually performed beyond 3 months
      postoperatively. Further studies are needed for confirmation of cure.

PMID- 24041675
TI  - Association of lower urinary tract symptom/benign prostatic hyperplasia measures
      with international index of erectile function 5 in middle-aged policemen of Korea
      and the role of metabolic syndrome and testosterone in their relationship.
AB  - OBJECTIVE: To evaluate which among the lower urinary tract symptom (LUTS)/benign
      prostatic hyperplasia (BPH) measures is the most relevant to erectile dysfunction
      (ED) and elucidate the role of metabolic syndrome (MetS) and testosterone in
      their relationship. METHODS: A total of 2564 policemen aged 40-59 years who had
      participated in a health examination were included. LUTS/BPH and ED were
      evaluated by the international prostate symptoms score (IPSS), transrectal
      ultrasonography, uroflowmetry, postvoid residual urine volume (PVR), and
      international index of erectile function questionnaire 5 (IIEF-5). Spearman
      correlation tests, multiple linear regression tests, and logistic regression
      analyses were used. RESULTS: The median age was 49.0 years; the median total IPSS
      and IIEF scores were 9 and 19, respectively. Among the LUTS/BPH measures, IPSS (r
      = -0.311, P <.001) showed the highest correlation coefficient with IIEF, followed
      by total prostate volume (r = -0.082, P <.001), PVR (r = -0.080, P <.001), and
      maximal flow rate (r = 0.049, P = .014). In addition, only IPSS was significantly
      correlated with the IIEF score after adjusting for age, testosterone, and MetS.
      The severity of LUTS, as assessed by IPSS, was also significantly correlated with
      moderate to severe ED (IIEF <= 11), after adjusting for age, testosterone, MetS,
      and other LUTS/BPH measures. On multiple linear regression test, adjustment of
      Mets changed the P value and beta value of LUTS/BPH measures. However, there were
      no changes after adjusting testosterone. CONCLUSION: IPSS is the most powerful
      predictor of ED among the LUTS/BPH measures in middle-aged policemen. In
      addition, MetS might be a plausible explanation for the relationship between
      LUTS/BPH and ED.

PMID- 24041676
TI  - CDH13 genotype-dependent association of high-molecular weight adiponectin with
      all-cause mortality: the J-SHIPP study.
AB  - OBJECTIVE: Despite its anti-inflammatory and antiatherogenic effects, adiponectin
      is potentially associated with adverse clinical outcomes, such as all-cause
      mortality. As plasma adiponectin levels are strongly influenced by single
      nucleotide polymorphisms in the gene encoding T-cadherin (CDH13), we conducted a
      longitudinal study to investigate the possible link between the CDH13 genotype,
      plasma adiponectin levels, and all-cause mortality. RESEARCH DESIGN AND METHODS:
      This longitudinal study evaluated 2,020 Japanese subjects. Baseline clinical
      parameters were obtained from subjects' personal health records as evaluated at
      annual medical check-ups. Plasma high-molecular weight adiponectin (HMWA) levels
      were measured by an ELISA assay, and genotyping was performed by a TaqMan probe
      assay. RESULTS: Mean follow-up duration was 6.5 years. Kaplan-Meier analysis
      showed that HMWA levels were positively associated with mortality (P < 0.001).
      HMWA levels were associated with older age, lower body weight, lower plasma
      triglyceride and glucose levels, and higher plasma HDL cholesterol. However, the
      Cox regression analysis showed that the positive association between HMWA and all
      cause mortality was independent of these covariates (hazard ratio [HR] 1.92, P =
      0.006). The CDH13 rs4783244 genotype was strongly associated with baseline HMWA
      levels (per-allele effect size 1.65 MUg/mL, P < 0.001). In a separate analysis by
      the CDH13 genotype, the HR for all-cause mortality was linearly increased with
      the number of G alleles (P value for HMWA-CDH13 genotype interaction = 0.023).
      CONCLUSIONS: Higher plasma HMWA level was an independent prognostic factor for
      all-cause mortality in a general population. The CDH13 genotype may be a factor
      that affects not only the plasma level of HMWA but also the prognostic
      significance of HMWA.

PMID- 24041677
TI  - Prevalence of diabetes in U.S. youth in 2009: the SEARCH for diabetes in youth
      study.
AB  - OBJECTIVE: To estimate the prevalence of diabetes in U.S. youth aged <20 years in
      2009 and to estimate the total number of youth with diabetes in the U.S. by age,
      race/ethnicity, and diabetes type. RESEARCH DESIGN AND METHODS: To address one of
      its primary aims, the SEARCH for Diabetes in Youth Study identified youth aged
      <20 years on 31 December 2009 with physician-diagnosed diabetes in selected areas
      of Colorado, Ohio, South Carolina, and Washington, among health plan members of
      Kaiser Permanente Southern California and among American Indians living on
      reservations in Arizona and New Mexico. Diabetes was classified as type 1, type
      2, or other. Race/ethnicity was by self-report. RESULTS: From a population of
      3,458,974 youth aged <20 years, 7,695 youth with diabetes were identified
      (2.22/1,000): 6,668 with type 1 diabetes (1.93/1,000), 837 with type 2 diabetes
      (0.24/1,000), and 190 (0.05/1,000) with other diabetes types. Prevalence
      increased with age, was slightly higher in females than males, and was most
      prevalent in non-Hispanic White and least prevalent in Asian/Pacific Islanders,
      with Native American and black youth having the highest prevalence of type 2
      diabetes. An estimated 191,986 U.S. youth aged <20 years have diabetes; 166,984
      type 1 diabetes, 20,262 type 2 diabetes, and 4,740 other types. CONCLUSIONS:
      Diabetes, one of the leading chronic diseases in childhood, affects >190,000 (1
      of 433) youth aged <20 years in the U.S., with racial and ethnic disparities seen
      in diabetes prevalence, overall and by diabetes type.

PMID- 24041678
TI  - Increased complement activation in human type 1 diabetes pancreata.
AB  - OBJECTIVE: Evidence supporting an association between complement (C) and type 1
      diabetes (T1D) includes the identification of C-fixing islet cell autoantibodies
      in T1D sera and genetic associations with the major histocompatibility complex
      III C4 region on chromosome 6. Therefore, we investigated whether C activation
      was present in pancreata from those with or at increased risk (positive for T1D
      associated autoantibodies) for T1D. RESEARCH DESIGN AND METHODS:
      Immunohistochemical techniques were used to measure the C degradation product C4d
      in organ donor pancreata from patients with T1D and type 2 diabetes and
      autoantibody-positive and autoantibody-negative subjects. RESULTS: Median C4d
      antigen density differed across the groups (P < 0.0001) and was highest in
      patients with T1D. C4d immunostaining localized to the blood vessel endothelium
      and extracellular matrix surrounding blood vessels and exocrine ducts. Receiver
      operating characteristic analysis resulted in 81.8% sensitivity and 94.4%
      specificity for C4d staining. CONCLUSIONS: These data suggest that C activation
      is occurring within pancreata from patients with T1D and C4d may be a biomarker
      for T1D.

PMID- 24041679
TI  - Highly sensitive diagnosis of 43 monogenic forms of diabetes or obesity through
      one-step PCR-based enrichment in combination with next-generation sequencing.
AB  - OBJECTIVE: Accurate etiological diagnosis of monogenic forms of diabetes and
      obesity is useful as it can lead to marked improvements in patient care and
      genetic counseling. Currently, molecular diagnosis based on Sanger sequencing is
      restricted to only a few genes, as this technology is expensive, time-consuming,
      and labor-intensive. High-throughput next-generation sequencing (NGS) provides an
      opportunity to develop innovative cost-efficient methods for sensitive diabetes
      and obesity multigene screening. RESEARCH DESIGN AND METHODS: We assessed a new
      method based on PCR enrichment in microdroplets (RainDance Technologies) and NGS
      using the Illumina HiSeq2000 for the molecular diagnosis of 43 forms of monogenic
      diabetes or obesity. Forty patients carrying a known causal mutation for those
      subtypes according to diagnostic laboratories were blindly reanalyzed. RESULTS:
      Except for one variant, we reidentified all causal mutations in each patient
      associated with an almost-perfect sequencing of the targets (mean of 98.6%). We
      failed to call one highly complex indel, although we identified a dramatic drop
      of coverage at this locus. In three patients, we detected other mutations with a
      putatively deleterious effect in addition to those reported by the genetic
      diagnostic laboratories. CONCLUSIONS: Our NGS approach provides an efficient
      means of highly sensitive screening for mutations in genes associated with
      monogenic forms of diabetes and obesity. As cost and time to deliver results have
      been key barriers to uncovering a molecular cause in the many undiagnosed cases
      likely to exist, the present methodology should be considered in patients
      displaying features of monogenic diabetes or obesity.

PMID- 24041680
TI  - Relationship between hypoglycemic episodes and ventricular arrhythmias in
      patients with type 2 diabetes and cardiovascular diseases: silent hypoglycemias
      and silent arrhythmias.
AB  - OBJECTIVE: In patients with type 2 diabetes and cardiovascular diseases (CVDs),
      intensive treatment with insulin and/or sulfonylurea (SU) may be associated with
      excessive increased risk of hypoglycemic episodes. To evaluate the risk of
      critical arrhythmias related to glycemic variability, we carried out an
      observational study in type 2 diabetes patients with CVD. RESEARCH DESIGN AND
      METHODS: Thirty patients with type 2 diabetes and documented CVD who had been
      treated with insulin and/or SU underwent 5 days of monitoring with a continuous
      glucose measurement system along with parallel electrocardiogram recording for
      monitoring of ventricular arrhythmias. Twelve age-matched patients with
      documented CVD who received treatment with metformin and/or dipeptidyl peptidase
      4 inhibitor served as the control group. Patients were receiving stable
      treatment, and were instructed to notice symptoms of arrhythmias and
      hypoglycemia, respectively. RESULTS: We observed a high incidence of asymptomatic
      severe episodes of hypoglycemia (<3.1 mmol/L) in patients receiving treatment
      with insulin and/or SU, whereas severe hypoglycemia did not develop in any of the
      control subjects. Patients with severe hypoglycemia (n = 12) had a higher number
      of severe ventricular arrhythmias (patients with versus without severe
      hypoglycemia, respectively: ventricular couplets 41.7 +/- 81.8 vs. 5.5 +/- 16.7;
      ventricular tachycardia 1.0 +/- 1.9 vs. 0.1 +/- 0.3). No direct correlation could
      be found among different variables of glucose profile, corrected QT interval, and
      ventricular arrhythmias. CONCLUSIONS: Our results suggest that severe episodes of
      hypoglycemia are associated with an increased risk of severe ventricular
      arrhythmias.

PMID- 24041681
TI  - Endocrine secretory reserve and proinsulin processing in recipients of islet of
      langerhans versus whole pancreas transplants.
AB  - OBJECTIVE: beta-Cells have demonstrated altered proinsulin processing after islet
      transplantation. We compare beta-cell metabolic responses and proinsulin
      processing in pancreas and islet transplant recipients with respect to healthy
      control subjects. RESEARCH DESIGN AND METHODS: We studied 15 islet and 32
      pancreas transplant recipients. Islet subjects were subdivided into insulin
      requiring (IR-ISL, n = 6) and insulin-independent (II-ISL, n = 9) groups. Ten
      healthy subjects served as control subjects. Subjects were administered an
      intravenous arginine stimulation test, and insulin, C-peptide, total proinsulin,
      intact proinsulin, and proinsulin fragment levels were determined from serum
      samples. Acute insulin response (AIR) and proinsulin processing rates were
      calculated. RESULTS: We found that basal insulin and C-peptide levels were higher
      in the pancreas group than in all other groups. II-ISL patients had basal insulin
      and C-peptide levels similar to healthy control subjects. The IR-ISL group had
      significantly lower AIRs than all other groups. Basal processing rates were
      higher in the pancreas and II-ISL groups than in healthy control subjects and the
      IR-ISL group. After arginine stimulation, all groups had elevated processing
      rates, with the exception of the IR-ISL group. CONCLUSIONS: Our data suggest that
      II-ISL transplant recipients can maintain basal metabolic parameters similar to
      healthy control subjects at the cost of a higher rate of proinsulin processing.
      IR-ISL transplant recipients, on the other hand, demonstrate both lower insulin
      response and lower basal rates of proinsulin processing even after arginine
      stimulation.

PMID- 24041682
TI  - Effect of moderate-intensity exercise versus activities of daily living on 24
      hour blood glucose homeostasis in male patients with type 2 diabetes.
AB  - OBJECTIVE: To investigate the impact of activities of daily living (ADL) versus
      moderate-intensity endurance-type exercise on 24-h glycemic control in patients
      with type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty males with type 2
      diabetes participated in a randomized crossover study consisting of three
      experimental periods of 3 days each. Subjects were studied under sedentary
      control conditions, and under conditions in which prolonged sedentary time was
      reduced either by three 15-min bouts of ADL (postmeal strolling, ~3 METs) or by a
      single 45-min bout of moderate-intensity endurance-type exercise (~6 METs). Blood
      glucose concentrations were assessed by continuous glucose monitoring, and plasma
      insulin concentrations were determined in frequently sampled venous blood
      samples. RESULTS: Hyperglycemia (glucose >10 mmol/L) was experienced for 6 h 51
      min +/-1 h 4 min per day during the sedentary control condition and was
      significantly reduced by exercise (4 h 47 min +/- 1 h 2 min; P < 0.001), but not
      by ADL (6 h 2 min +/- 1 h 16 min; P = 0.67). The cumulative glucose incremental
      areas under the curve (AUCs) of breakfast, lunch, and dinner were, respectively,
      35 +/- 5% (P < 0.001) and 17 +/- 6% (P < 0.05) lower during the exercise and ADL
      conditions compared with the sedentary condition. The insulin incremental AUCs
      were, respectively, 33 +/- 4% (P < 0.001) and 17 +/- 5% (P < 0.05) lower during
      the exercise and ADL conditions compared with the sedentary condition.
      CONCLUSIONS: When matched for total duration, moderate-intensity endurance-type
      exercise represents a more effective strategy to improve daily blood glucose
      homeostasis than repeated bouts of ADL. Nevertheless, the introduction of
      repeated bouts of ADL during prolonged sedentary behavior forms a valuable
      strategy to improve postprandial glucose handling in patients with type 2
      diabetes.

PMID- 24041683
TI  - Minimal functional beta-cell mass in intraportal implants that reduces glycemic
      variability in type 1 diabetic recipients.
AB  - OBJECTIVE: Previous work has shown a correlation between beta-cell number in
      cultured islet cell grafts and their ability to induce C-peptide secretion after
      intraportal implantation in C-peptide-negative type1 diabetic patients. In this
      cross-sectional study, we examined the minimal functional beta-cell mass (FBM) in
      the implant that induces metabolic improvement. RESEARCH DESIGN AND METHODS:
      Glucose clamps assessed FBM in 42 recipients with established implants. C-peptide
      release during each phase was expressed as percentage of healthy control values.
      Its relative magnitude during a second hyperglycemic phase was most
      discriminative and therefore selected as a parameter to be correlated with
      metabolic effects. RESULTS: Recipients with functioning beta-cell implants
      exhibited average FBM corresponding to 18% of that in normal control subjects
      (interquartile range 10-33%). Its relative magnitude negatively correlated with
      HbA1c levels (r = -0.47), daily insulin dose (r = -0.75), and coefficient of
      variation of fasting glycemia (CVfg) (r = -0.78, retained in multivariate
      analysis). A correlation between FBM and CVfg <25% appeared from the receiver
      operating characteristic curve (0.97 [95% CI 0.93-1.00]). All patients with FBM
      >37% exhibited CVfg <25% and a >50% reduction of their pretransplant CVfg; this
      occurred in none with FBM <5%. Implants with FBM >18% reduced CVfg from a median
      pretransplant value of 46 to <25%. CONCLUSIONS: Glucose clamping assesses the
      degree of restoration in FBM achieved by islet cell implants. Values >37% of
      normal control subjects appear needed to reduce glycemic variability in type 1
      diabetic recipients. Further studies should examine whether the test can help
      guide decisions on additional islet cell transplants and on adjusting or stopping
      immunotherapy.

PMID- 24041684
TI  - Factors associated with maternal-reported actions to prevent type 1 diabetes in
      the first year of the TEDDY study.
AB  - OBJECTIVE: Mothers of children at risk for type 1 diabetes report engaging in
      preventive behaviors. The purpose of this study is to further document these
      actions in an international, longitudinal sample and examine variables that
      predict whether mothers engage in these behaviors. RESEARCH DESIGN AND METHODS:
      This study examined an international sample (from Finland, Germany, Sweden, and
      the U.S.) from the naturalistic, longitudinal The Environmental Determinants of
      Diabetes in the Young (TEDDY) study, which tracked children genetically at risk
      for type 1 diabetes from birth to age 15 years. Mothers of 7,613 infants aged 6
      months and 6,503 infants aged 15 months completed questionnaires assessing
      psychosocial factors and actions intended to prevent diabetes. RESULTS: Many
      mothers (29.9% at 6 months and 42.8% at 15 months) reported engaging in a
      behavior intended to prevent type 1 diabetes, with the largest percentages (20.9
      29.2%) reporting making changes to their child's diet (e.g., reducing the
      consumption of sweets and carbohydrates). Factors related to engaging in
      preventive behaviors include older maternal age; higher maternal education;
      minority status; having only one child; having a first-degree relative with type
      1 diabetes; being from a country other than Sweden; having an accurate perception
      of the child's increased risk for developing diabetes; having postpartum
      depression, maternal anxiety, and worry about the risk of diabetes; and believing
      that diabetes can be prevented. CONCLUSIONS: The findings of this study suggest
      that many mothers engage in actions to prevent diabetes and highlight the
      importance of tracking these behaviors to ensure the validity of naturalistic
      observational studies.

PMID- 24041685
TI  - Function of the head-tail junction in the activity of myosin II.
AB  - All class II myosins have the conserved amino acid sequence Pro-Leu-Leu at their
      head-tail junctions. We systematically altered this sequence in smooth muscle
      heavy meromyosin (HMM) by site-directed mutagenesis and examined the effects of
      these mutations on actin-myosin interactions. Deletion of the proline and second
      leucine did not cause any noticeable change in either actin-activated ATPase
      activity or actin-sliding velocity. In contrast, deletion of the two leucine
      residues and substitution of the first leucine with alanine resulted in a 14-fold
      and 5-fold decrease, respectively, in actin-activated ATPase activity. However,
      both these mutations did not appreciably affect actin-sliding velocity, which was
      consistent with a result that there was no considerable change in the ADP release
      rate from acto-HMM in the deletion mutant. In contrast to double-headed HMM, a
      single-headed subfragment-1 (S1) with a Leu-Leu deletion mutation exhibited actin
      activated ATPase activity similar to that by wild type S1. Our results suggest
      that the first leucine of the conserved Leu-Leu sequence at the head-tail
      junction profoundly affects the cooperativity between the two heads involved in
      the actin activated ATPase activity of myosin II. 

PMID- 24041686
TI  - Quantitative proteomic analysis by iTRAQ for identification of candidate
      biomarkers in plasma from acute respiratory distress syndrome patients.
AB  - Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and
      mortality in critical patients. Proteomic analysis of plasma from individuals
      with ARDS could elucidate new biomarkers for diagnosis and pathophysiology and
      identify potential ARDS treatment targets. In this study, we recruited 26
      patients (15 controls, 11 ARDS). The ARDS group was subdivided into two groups
      depending on the type of injury: (1) direct lung injury (AD) and (2) indirect
      lung injury (AI). Using iTRAQ (isobaric tags for relative and absolute
      quantitation) analysis, we identified 2429 peptides representing 132 plasma
      proteins. Among these, 16 were differentially expressed in ARDS patients,
      including 11 overlapping proteins between the AI and AD group and 5 AI-specific
      proteins. Protein annotation revealed that lipid transport and complement
      activation were significantly enriched in the biological process category, and
      lipid transporter, transporter, and serine-type peptidase activities were
      significantly enriched in the molecular function category. IPA (Ingenuity Pathway
      Analysis) signaling pathways revealed that the overlapping proteins were involved
      in a variety of signaling pathways, including those underlying acute phase
      response; liver X receptor/retinoid X receptor (LXR/RXR) and farnesoid X
      (FXR)/RXR activation; clathrin-mediated endocytosis; atherosclerosis; interleukin
      (IL)-12; complement system; and cytokine, nitric oxide, and reactive oxygen
      species production in macrophages. We present the first proteomic analysis of
      ARDS plasma using the iTRAQ approach. Our data provide new biomarker candidates
      and shed light on potential pathological mechanisms underlying ARDS. 

PMID- 24041687
TI  - Modest hypoxia significantly reduces triglyceride content and lipid droplet size
      in 3T3-L1 adipocytes.
AB  - BACKGROUND: A previous study has demonstrated that endurance training under
      hypoxia results in a greater reduction in body fat mass compared to exercise
      under normoxia. However, the cellular and molecular mechanisms that underlie this
      hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the
      effects of modest hypoxia on adipocyte function. METHODS: Differentiated 3T3-L1
      adipocytes were incubated at 5% O2 for 1 week (long-term hypoxia, HL) or one day
      (short-term hypoxia, HS) and compared with a normoxia control (NC). RESULTS: HL,
      but not HS, resulted in a significant reduction in lipid droplet size and
      triglyceride content (by 50%) compared to NC (p<0.01). As estimated by glycerol
      release, isoproterenol-induced lipolysis was significantly lowered by hypoxia,
      whereas the release of free fatty acids under the basal condition was prominently
      enhanced with HL compared to NC or HS (p<0.01). Lipolysis-associated proteins,
      such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose
      triglyceride lipase and its activator protein CGI-58 were decreased with HL in
      comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase,
      lipin-1, and peroxisome proliferator-activated receptor gamma were decreased.
      Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate
      for triglyceride synthesis, was significantly reduced in HL compared to NC or HS
      (p<0.01). CONCLUSION: We conclude that hypoxia has a direct impact on reducing
      the triglyceride content and lipid droplet size via decreased glucose uptake and
      lipogenic protein expression and increased basal lipolysis. Such an hypoxia
      induced decrease in lipogenesis may be an attractive therapeutic target against
      lipid-associated metabolic diseases.

PMID- 24041689
TI  - A DNA vaccine against cytotoxic T-lymphocyte associated antigen-4 (CTLA-4)
      prevents tumor growth.
AB  - Co-stimulatory signaling pathway triggered by the binding of B7.1/B7.2 (CD80/86)
      of antigen-presenting cells (APCs) to CD28 of T cells is required for optimal T
      cell activation. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is a
      negative regulator of T cell activation, which competes with CD28 for B7.1/B7.2
      binding with a greater affinity. Ipilimumab, a monoclonal antibody against CTLA
      4, has shown positive efficacy in a pivotal clinical trial for the treatment of
      metastatic melanoma and was approved by FDA. However, the cost of monoclonal
      antibody-based therapeutics might limit the number of patients treated. To
      develop a novel therapeutics specifically targeting CTLA-4, we constructed a DNA
      vaccine by cloning the sequence of CTLA-4 fused with a transmembrane domain
      sequence of placental alkaline phosphatase (PLAP) into a mammalian expression
      plasmid, pVAC-1. Immunization with the resulting construct, pVAC-1-hCTLA-4,
      elicited antibody specific to human CTLA-4 with cross reactivity to murine CTLA
      4, which was sufficient for inhibiting B16F10 tumor growth in c57BL/6 mice in the
      absence of measurable toxicity. Coupling liposome with pVAC-1-mCTLA-4 could break
      tolerance to self-antigen in BALB/c mice and induce potent immunity against
      murine CTLA-4, and suppress growth of subcutaneous renal cell carcinoma (Renca).

PMID- 24041688
TI  - Targeting SHP2 for EGFR inhibitor resistant non-small cell lung carcinoma.
AB  - Targeted therapy with inhibitors of epidermal growth factor receptor (EGFR) has
      produced a noticeable benefit to non-small cell lung cancer (NSCLC) patients
      whose tumors carry activating mutations (e.g. L858R) in EGFR. Unfortunately,
      these patients develop drug resistance after treatment, due to acquired secondary
      gatekeeper mutations in EGFR (e.g. T790M). Given the critical role of SHP2 in
      growth factor receptor signaling, we sought to determine whether targeting SHP2
      could have therapeutic value for EGFR inhibitor resistant NSCLC. We show that
      SHP2 is required for EGF-stimulated ERK1/2 phosphorylation and proliferation in
      EGFR inhibitor resistant NSCLC cell line H1975, which harbors the EGFR
      T790M/L858R double-mutant. We demonstrate that treatment of H1975 cells with II
      B08, a specific SHP2 inhibitor, phenocopies the observed growth inhibition and
      reduced ERK1/2 activation seen in cells treated with SHP2 siRNA. Importantly, we
      also find that II-B08 exhibits marked anti-tumor activity in H1975 xenograft
      mice. Finally, we observe that combined inhibition of SHP2 and PI3K impairs both
      the ERK1/2 and PI3K/AKT signaling axes and produces significantly greater effects
      on repressing H1975 cell growth than inhibition of either protein individually.
      Collectively, these results suggest that targeting SHP2 may represent an
      effective strategy for treatment of EGFR inhibitor resistant NSCLCs. 

PMID- 24041690
TI  - Episodic positive selection during the evolution of naphthalene dioxygenase to
      nitroarene dioxygenase.
AB  - Using different maximum-likelihood models of adaptive evolution, signatures of
      natural selective pressure, operating across the naphthalene family of
      dioxygenases, were examined. A lineage- and branch-site specific combined
      analysis revealed that purifying selection pressure dominated the evolutionary
      history of the enzyme family. Specifically, episodic positive Darwinian selection
      pressure, affecting only a few sites in a subset of lineages, was found to be
      responsible for the evolution of nitroarene dioxygenases (NArDO) from naphthalene
      dioxygenase (NDO). Site-specific analysis confirmed the absence of diversifying
      selection pressure at any particular site. Different sets of positively selected
      residues, obtained from branch-site specific analysis, were detected for the
      evolution of each NArDO. They were mainly located around the active site, the
      catalytic pocket and their adjacent regions, when mapped onto the 3D structure of
      the alpha-subunit of NDO. The present analysis enriches the current understanding
      of adaptive evolution and also broadens the scope for rational alteration of
      substrate specificity of enzyme by directed evolution. 

PMID- 24041691
TI  - Tyrosine nitration moderates the peptidase activity of human methionyl
      aminopeptidase 2.
AB  - Methionyl aminopeptidase 2 (MetAP2) plays an important role in the regulation of
      angiogenesis. This study examined whether nitration of MetAP2 alters its
      enzymatic activity in vitro. The activity of unmodified, nitrated and oxidised
      MetAP2 was assessed and it was found that nitration significantly reduced its
      ability to cleave a chromogenic substrate. Mass spectrometry analysis identified
      Tyr336 as a nitrated residue in MetAP2. Structural and evolutionary analysis
      indicate that this is an important residue for MetAP2 activity. Combined, the
      results show that the activity of MetAP2 is reduced by nitration and raise the
      possibility that nitration of MetAP2 is a mechanism contributing to endothelial
      dysfunction.

PMID- 24041692
TI  - Trisomy of the Dscr1 gene suppresses early progression of pancreatic
      intraepithelial neoplasia driven by oncogenic Kras.
AB  - Individuals with Down syndrome exhibit remarkably reduced incidence of most solid
      tumors including pancreatic cancer. Multiple mechanisms arising from the genetic
      complexity underlying Down syndrome has been suggested to contribute to such a
      broad cancer protection. In this study, utilizing a genetically engineered mouse
      model of pancreatic cancer, we demonstrate that trisomy of the Down syndrome
      critical region-1 (Dscr1), an endogenous calcineurin inhibitor localized on
      chromosome 21, suppresses the progression of pancreatic intraepithelial neoplasia
      1A (PanIN-1A) to PanIN-1B lesions without affecting the initiation of PanIN
      lesions mediated by oncogenic Kras(G12D). In addition, we show that Dscr1 trisomy
      attenuates nuclear localization of nuclear factor of activated T-cells (NFAT)
      accompanied by upregulation of the p15(Ink4b) tumor suppressor and reduction of
      cell proliferation in early PanIN lesions. Our data suggest that attenuation of
      calcineurin-NFAT signaling in neoplastic pancreatic ductal epithelium by a single
      extra copy of Dscr1 is sufficient to inhibit the progression of early PanIN
      lesions driven by oncogenic Kras, and thus may be a potential mechanism
      underlying reduced incidence of pancreatic cancer in Down syndrome individuals.

PMID- 24041693
TI  - Identification of FAM96B as a novel prelamin A binding partner.
AB  - Prelamin A accumulation causes nuclear abnormalities, impairs nuclear functions,
      and eventually promotes cellular senescence. However, the underlying mechanism of
      how prelamin A promotes cellular senescence is still poorly understood. Here we
      carried out a yeast two-hybrid screen using a human skeletal muscle cDNA library
      to search for prelamin A binding partners, and identified FAM96B as a prelamin A
      binding partner. The interaction of FAM96B with prelamin A was confirmed by GST
      pull-down and co-immunoprecipitation experiments. Furthermore, co-localization
      experiments by fluorescent confocal microscopy revealed that FAM96B colocalized
      with prelamin A in HEK-293 cells. Taken together, our data demonstrated the
      physical interaction between FAM96B and prelamin A, which may provide some clues
      to the mechanisms of prelamin A in premature aging. 

PMID- 24041694
TI  - Metformin-induced inhibition of the mitochondrial respiratory chain increases
      FGF21 expression via ATF4 activation.
AB  - Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exhibits anti
      obesity and anti-diabetes effects. Because metformin is widely used as a glucose
      lowering agent in patients with type 2 diabetes (T2D), we investigated whether
      metformin modulates FGF21 expression in cell lines, and in mice or human
      subjects. We found that metformin increased the expression and release of FGF21
      in a diverse set of cell types, including rat hepatoma FaO, primary mouse
      hepatocytes, and mouse embryonic fibroblasts (MEFs). Intriguingly, AMP-activated
      protein kinase (AMPK) was dispensable for the induction of FGF21 by metformin.
      Mammalian target of rapamycin complex 1 (mTORC1) and peroxisome proliferator
      activated receptor alpha (PPARalpha), which are additional targets of metformin,
      were not involved in metformin-induced FGF21 expression. Importantly, inhibition
      of mitochondrial complex I activity by metformin resulted in FGF21 induction
      through PKR-like ER kinase (PERK)-eukaryotic translation factor 2alpha
      (eIF2alpha)-activating transcription factor 4 (ATF4). We showed that metformin
      activated ATF4 and increased FGF21 expression in the livers of mice, which led to
      increased serum levels of FGF21. We also found that serum FGF21 level was
      increased in human subjects with T2D after metformin therapy for 6 months. In
      conclusion, our results indicate that metformin induced expression of FGF21
      through an ATF4-dependent mechanism by inhibiting mitochondrial respiration
      independently of AMPK. Therefore, FGF21 induction by metformin might explain a
      portion of the beneficial metabolic effects of metformin.

PMID- 24041695
TI  - Inhibition of fatty acid synthase suppresses U-2 OS cell invasion and migration
      via downregulating the activity of HER2/PI3K/AKT signaling pathway in vitro.
AB  - FASN plays an important role in the malignant phenotype of various tumors. Our
      previous studies show that inhibition FASN could induce apoptosis and inhibit
      proliferation in human osteosarcoma (OS) cell in vivo and vitro. The aim in this
      study was to investigate the effect of inhibition FASN on the activity of
      HER2/PI3K/AKT axis and invasion and migration of OS cell. The expression of FASN,
      HER2 and p-HER2(Y1248) proteins was detected by immunohistochemistry in OS
      tissues from 24 patients with pulmonary metastatic disease, and the relationship
      between FASN and p-HER2 as well as HER2 was investigated. The results showed that
      there was a positive correlation between FASN and HER2 as well as p-HER2 protein
      expression. The U-2 OS cells were transfected with either the FASN specific RNAi
      plasmid or the negative control RNAi plasmid. FASN mRNA was measured by RT-PCR.
      Western blot assays was performed to examine the protein expression of FASN,
      HER2, p-HER2(Y1248), PI3K, Akt and p-Akt (Ser473). Migration and invasion of
      cells were investigated by wound healing and transwell invasion assays. The
      results showed that the activity of HER2/PI3K/AKT signaling pathway was
      suppressed by inhibiting FASN. Meanwhile, the U-2OS cells migration and invasion
      were also impaired by inhibiting the activity of FASN/HER2/PI3K/AKT. Our results
      indicated that inhibition of FASN suppresses OS cell invasion and migration via
      down-regulation of the "HER2/PI3K/AKT" axis in vitro. FASN blocker may be a new
      therapeutic strategy in OS management.

PMID- 24041696
TI  - GTDC2 modifies O-mannosylated alpha-dystroglycan in the endoplasmic reticulum to
      generate N-acetyl glucosamine epitopes reactive with CTD110.6 antibody.
AB  - Hypoglycosylation is a common characteristic of dystroglycanopathy, which is a
      group of congenital muscular dystrophies. More than ten genes have been
      implicated in alpha-dystroglycanopathies that are associated with the defect in
      the O-mannosylation pathway. One such gene is GTDC2, which was recently reported
      to encode O-mannose beta-1,4-N-acetylglucosaminyltransferase. Here we show that
      GTDC2 generates CTD110.6 antibody-reactive N-acetylglucosamine (GlcNAc) epitopes
      on the O-mannosylated alpha-dystroglycan (alpha-DG). Using the antibody, we show
      that mutations of GTDC2 identified in Walker-Warburg syndrome and alanine
      substitution of conserved residues between GTDC2 and EGF domain O-GlcNAc
      transferase resulted in decreased glycosylation. Moreover, GTDC2-modified GlcNAc
      epitopes are localized in the endoplasmic reticulum (ER). These data suggested
      that GTDC2 is a novel glycosyltransferase catalyzing GlcNAcylation of O
      mannosylated alpha-DG in the ER. CTD110.6 antibody may be useful to detect a
      specific form of GlcNAcylated O-mannose and to analyze defective O-glycosylation
      in alpha-dystroglycanopathies.

PMID- 24041697
TI  - The effect of exposing a critical hydrophobic patch on amyloidogenicity and
      fibril structure of insulin.
AB  - It is widely accepted that the formation of amyloid fibrils is one of the natural
      properties of proteins. The amyloid formation process is associated with a
      variety of factors, among which the hydrophobic residues play a critical role. In
      this study, insulin was used as a model to investigate the effect of exposing a
      critical hydrophobic patch on amyloidogenicity and fibril structure of insulin.
      Porcine insulin was digested with trypsin to obtain desoctapeptide-(B23-B30)
      insulin (DOI), whose hydrophilic C-terminal of B-chain was removed and
      hydrophobic core was exposed. The results showed that DOI, of which the ordered
      structure (predominantly alpha-helix) was markedly decreased, was more prone to
      aggregate than intact insulin. As to the secondary structure of amyloid fibrils,
      DOI fibrils were similar to insulin fibrils formed under acidic condition,
      whereas under neutral condition, insulin formed less polymerized aggregates by
      showing decreased beta-sheet contents in fibrils. Further investigation on
      membrane damage and hemolysis showed that DOI fibrils induced significantly less
      membrane damage and less hemolysis of erythrocytes compared with those of insulin
      fibrils. In conclusion, exposing the hydrophobic core of insulin can induce the
      increase of amyloidogenicity and formation of higher-order polymerized fibrils,
      which is less toxic to membranes.

PMID- 24041698
TI  - Expression profile and function of Wnt signaling mechanisms in malignant
      mesothelioma cells.
AB  - Malignant mesothelioma (MM) is an uncommon and particularly aggressive cancer
      associated with asbestos exposure, which currently presents an intractable
      clinical challenge. Wnt signaling has been reported to play a role in the
      neoplastic properties of mesothelioma cells but has not been investigated in
      detail in this cancer. We surveyed expression of Wnts, their receptors, and other
      key molecules in this pathway in well established in vitro mesothelioma models in
      comparison with primary mesothelial cultures. We also tested the biological
      response of MM cell lines to exogenous Wnt and secreted regulators, as well as
      targeting beta-catenin. We detected frequent expression of Wnt3 and Wnt5a, as
      well as Fzd 2, 4 and 6. The mRNA of Wnt4, Fzd3, sFRP4, APC and axin2 were
      downregulated in MM relative to mesothelial cells while LEF1 was overexpressed in
      MM. Functionally, we observed that Wnt3a stimulated MM proliferation while sFRP4
      was inhibitory. Furthermore, directly targeting beta-catenin expression could
      sensitise MM cells to cytotoxic drugs. These results provide evidence for altered
      expression of a number of Wnt/Fzd signaling molecules in MM. Modulation of Wnt
      signaling in MM may prove a means of targeting proliferation and drug resistance
      in this cancer.

PMID- 24041699
TI  - Antifungal effect of CopA3 monomer peptide via membrane-active mechanism and
      stability to proteolysis of enantiomeric D-CopA3.
AB  - In our previous study, coprisin, a 43-mer defensin-like peptide, was derived from
      the dung beetle, Copris tripartitus, and a 9-mer CopA3 (monomer), truncated
      coprisin analog peptide, was designed. However, the antifungal effects of CopA3
      are not known yet. In this study, the antifungal activity and mechanism of CopA3
      were investigated and to develop a more effective antimicrobial peptide under
      physiological conditions, the enantiomeric d-CopA3 was designed. l- and d-CopA3
      had a similar antifungal activity without chiral selectivity, and their activity
      was more potent than that of melittin used as a positive control. Furthermore, l-
      and d-CopA3 did not even show any hemolysis against human erythrocytes. Membrane
      studies using propidium iodide and bis-(1,3-dibutylbarbituric acid) trimethine
      oxonol [DiBAC4(3)], suggested that the antifungal effect of l- and d-CopA3 was
      due to the membrane-active mechanism, by contrast with coprisin possessing
      apoptotic mechanism without membrane permeabilization. Finally, the proteolytic
      resistance and antifungal activity of l- and d-CopA3 against trypsin was analyzed
      by HPLC and colony count assay. The results showed that only d-CopA3 maintained a
      potent antifungal activity despite the proteolytic condition. Therefore, this
      study suggests that d-CopA3 has potential as a novel antimicrobial agent.

PMID- 24041700
TI  - GATA4 loss-of-function mutation underlies familial dilated cardiomyopathy.
AB  - The cardiac transcription factor GATA4 is essential for cardiac development, and
      mutations in this gene have been implicated in a wide variety of congenital heart
      diseases in both animal models and humans. However, whether mutated GATA4
      predisposes to dilated cardiomyopathy (DCM) remains unknown. In this study, the
      whole coding region and splice junction sites of the GATA4 gene was sequenced in
      110 unrelated patients with idiopathic DCM. The available relatives of the index
      patient harboring an identified mutation and 200 unrelated ethnically matched
      healthy individuals used as controls were genotyped. The functional effect of the
      mutant GATA4 was characterized in contrast to its wild-type counterpart using a
      luciferase reporter assay system. As a result, a novel heterozygous GATA4
      mutation, p.C271S, was identified in a family with DCM inherited as an autosomal
      dominant trait, which co-segregated with DCM in the family with complete
      penetrance. The missense mutation was absent in 400 control chromosomes and the
      altered amino acid was completely conserved evolutionarily among species.
      Functional analysis demonstrated that the GATA4 mutant was associated with
      significantly decreased transcriptional activity and remarkably reduced
      synergistic activation between GATA4 and NKX2-5, another transcription factor
      crucial for cardiogenesis. The findings provide novel insight into the molecular
      mechanisms involved in the pathogenesis of DCM, suggesting the potential
      implications in the prenatal diagnosis and gene-specific treatment for this
      common form of myocardial disorder.

PMID- 24041701
TI  - Authentic Gettier cases: a reply to Starmans and Friedman.
AB  - Do laypeople and philosophers differ in their attributions of knowledge? Starmans
      and Friedman maintain that laypeople differ from philosophers in taking
      'authentic evidence' Gettier cases to be cases of knowledge. Their reply
      helpfully clarifies the distinction between 'authentic evidence' and 'apparent
      evidence'. Using their sharpened presentation of this distinction, we contend
      that the argument of our original paper still stands. 

PMID- 24041702
TI  - Digital subtraction angiography of the pelvis.

PMID- 24041704
TI  - Managing cows' milk allergy in children.

PMID- 24041703
TI  - Quantification of harms in cancer screening trials: literature review.
AB  - OBJECTIVES: To assess how often harm is quantified in randomised trials of cancer
      screening. DESIGN: Two authors independently extracted data on harms from
      randomised cancer screening trials. Binary outcomes were described as proportions
      and continuous outcomes with medians and interquartile ranges. DATA SOURCES: For
      cancer screening previously assessed in a Cochrane review, we identified trials
      from their reference lists and updated the search in CENTRAL. For cancer
      screening not assessed in a Cochrane review, we searched CENTRAL, Medline, and
      Embase. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials that
      assessed the efficacy of cancer screening for reducing incidence of cancer,
      cancer specific mortality, and/or all cause mortality. DATA EXTRACTION: Two
      reviewers independently assessed articles for eligibility. Two reviewers, who
      were blinded to the identity of the study's authors, assessed whether absolute
      numbers or incidence rates of outcomes related to harm were provided separately
      for the screening and control groups. The outcomes were false positive findings,
      overdiagnosis, negative psychosocial consequences, somatic complications,
      invasive follow-up procedures, all cause mortality, and withdrawals because of
      adverse events. RESULTS: Out of 4590 articles assessed, 198 (57 trials, 10
      screening technologies) matched the inclusion criteria. False positive findings
      were quantified in two of 57 trials (4%, 95% confidence interval 0% to 12%),
      overdiagnosis in four (7%, 2% to 18%), negative psychosocial consequences in five
      (9%, 3% to 20%), somatic complications in 11 (19%, 10% to 32%), use of invasive
      follow-up procedures in 27 (47%, 34% to 61%), all cause mortality in 34 (60%, 46%
      to 72%), and withdrawals because of adverse effects in one trial (2%, 0% to 11%).
      The median percentage of space in the results section that reported harms was 12%
      (interquartile range 2-19%). CONCLUSIONS: Cancer screening trials seldom quantify
      the harms of screening. Of the 57 cancer screening trials examined, the most
      important harms of screening--overdiagnosis and false positive findings--were
      quantified in only 7% and 4%, respectively.

PMID- 24041705
TI  - Guide aims to help patients be wary of "miracle cures".

PMID- 24041706
TI  - Educating practice staff about chlamydia boosts detection in young adults.

PMID- 24041707
TI  - UK clinical trials must be registered to win ethics committee approval.

PMID- 24041708
TI  - Ultrasonography in the diagnosis and management of patients with inflammatory
      arthritides.
AB  - In primary care and internal medicine settings clinicians are often reluctant to
      take advantage of the resources that ultrasonography (US) offers as a diagnostic
      tool in the initial management of patients with inflammatory arthritis, despite
      the recognised importance of an accurate and timely diagnosis of rheumatoid
      arthritis (RA) and of early referral to ensure optimal patient management. Both
      grey-scale (GS) and power Doppler (PD) imaging have been extensively used in
      early detection of synovitis and bone erosions in patients with inflammatory
      arthritides. We reviewed the main data on the clinical use of US in the initial
      management of patients with inflammatory arthritis, focusing on RA diagnosis in
      patients with undifferentiated arthritis, prediction of disease severity,
      differential diagnoses and assessment of synovitis in children with juvenile
      idiopathic arthritis (JIA). The role of US in assessing treatment response and
      monitoring disease activity in clinical remission was also briefly evaluated. The
      reliability of US as a diagnostic tool in rheumatological diseases has greatly
      advanced in the last years and the use of this imaging technique, in association
      with conventional assessments such as physical examination and serological tests,
      should be considered more often also in primary care settings. 

PMID- 24041709
TI  - HPMA copolymer-based combination therapy toxic to both prostate cancer
      stem/progenitor cells and differentiated cells induces durable anti-tumor
      effects.
AB  - Current treatments for prostate cancer are still not satisfactory, often
      resulting in tumor regrowth and metastasis. One of the main reasons for the
      ineffective anti-prostate cancer treatments is the failure to deplete cancer stem
      like cells (CSCs) - a subset of cancer cells with enhanced tumorigenic capacity.
      Thus, combination of agents against both CSCs and bulk tumor cells may offer
      better therapeutic benefits. Several molecules with anti-cancer stem/progenitor
      cell activities have been under preclinical evaluations. However, their low
      solubility and nonspecific toxicity limit their clinical translation. Herein, we
      designed a combination macromolecular therapy containing two drug conjugates:
      HPMA copolymer-cyclopamine conjugate (P-CYP) preferentially toxic to cancer
      stem/progenitor cells, and HPMA copolymer-docetaxel conjugate (P-DTX) effective
      in debulking the tumor mass. Both conjugates were synthesized using RAFT
      (reversible addition-fragmentation chain transfer) polymerization resulting in
      narrow molecular weight distribution. The killing effects of the two conjugates
      against bulk tumor cells and CSCs were evaluated in vitro and in vivo. In PC-3 or
      RC-92a/hTERT prostate cancer cells, P-CYP preferentially kills and impairs the
      function of CD133+ prostate cancer stem/progenitor cells; P-DTX was able to kill
      bulk tumor cells instead of CSCs. In a PC-3 xenograft mice model, combination of
      P-DTX and P-CYP showed the most effective and persistent tumor growth inhibitory
      effect. In addition, residual tumors contained less CD133+ cancer cells following
      combination or P-CYP treatments, indicating selective killing of cancer cells
      with stem/progenitor cell properties. 

PMID- 24041710
TI  - beta-Glucan microparticles are good candidates for mucosal antigen delivery in
      oral vaccination.
AB  - Continuously improving the developmental process and the efficacy of oral
      vaccines is essential in the fight against intestinal pathogens. A promising
      strategy for vaccination applying safe, biodegradable and non-replicating antigen
      delivery systems has gained increased interest for eliciting cellular and humoral
      immune responses. The current study evaluates the potential of beta-glucan
      particles (GP) as an oral antigen delivery system and their adjuvant
      characteristics. GP are efficiently internalized by human intestinal epithelial
      cell lines (Caco-2 and HT-29 cells), without exerting negative effects on cell
      viability. GP triggered the expression of pro-inflammatory cytokines IL-23p19, IL
      8 and the beta-glucan receptors dectin-1 and TLR2 by activated Caco-2 cells, and
      CCL20 in HT-29 cells. In contrast, the expression level of TGF-beta, an important
      mediator of oral tolerance, was significantly downregulated in HT-29 cells.
      Additionally, adoptive transfer experiments showed proliferating ovalbumin (OVA)
      specific CD4(+) T cells mainly in the spleens of GP-OVA-fed mice. Furthermore, we
      detected a significantly increased IL-17 and a trend towards increased IFN-gamma
      production in the spleen of GP-OVA-fed mice upon antigen restimulation. Oral
      administration of GP-OVA induced increased OVA-specific IgA, secretory-IgA (S
      IgA) and secretory component (SC) production in intestinal fluids. Our data show
      that GP vehicles are able to deliver OVA via an oral route allowing efficient
      antigen presentation alongside adaptive immune activation, resulting in a Th17
      biased response and the production of OVA-specific IgA, secretory-IgA and
      secretory component antibodies. 

PMID- 24041711
TI  - Efficient delivery of therapeutic small nucleic acids to prostate cancer cells
      using ketal nucleoside lipid nanoparticles.
AB  - A novel nucleoside lipid derived from dioleyl ketal was synthesized from uridine
      in three steps starting from dioleyl ketone. Electronic microscopy studies show
      that Ketals Nucleoside Lipids (KNL) self-assemble to form liposome-like
      structures in aqueous solutions. KNL is able to bind siRNA as demonstrated by
      electrophoresis experiment and standard ethidium bromide fluorescence
      displacement assay. Transfection assays of stable hepatic cell lines HupIRF,
      carrying a luciferase reporter gene demonstrate that KNL is able to transfect
      siRNA and exhibits protein knockdown more efficiently than its diester analog
      (DOTAU) and lipofectamine. Herein, we also report that KNLs are suitable
      transfecting reagents for the development of novel therapeutic approaches
      involving either siRNA or antisense oligonucleotide against human prostate cancer
      PC-3 cells resistant to chemotherapy. 

PMID- 24041712
TI  - Systematic review and meta-analysis of audio-visual information aids for informed
      consent for invasive healthcare procedures in clinical practice.
AB  - OBJECTIVE: To systematically review audio-visual (AV) interventions for promoting
      informed consent (IC) in clinical practice and to consider the impact of reading
      age adjustment. METHODS: Systematic review of randomized controlled trials (RCTs)
      comparing AV interventions to standard IC in clinical practice. Outcomes included
      recall (immediate <1 day; intermediate 1-14 days; late >14 days), satisfaction
      and anxiety. Data were synthesized using random effects meta-analyses.
      Comparisons were made between studies that did and did not adjust for participant
      reading age. RESULTS: Of 11,813 abstracts screened, 29 RCTs were eligible (30
      intervention arms). Interventions included videos (n=17), computer programs
      (n=5), electronic presentations (n=3), compact discs (n=3) and websites (n=2).
      Meta-analysis showed AV interventions improved immediate recall (standardized
      mean difference [SMD] 0.64, 95% confidence interval [CI] 0.45-0.85). Results for
      intermediate and late recall were too heterogeneous to synthesize. AV
      interventions did not consistently affect either satisfaction or anxiety.
      Adjusting the reading age of interventions improved immediate recall (reading age
      interventions: adjusted SMD 1.21, 95%CI 0.81-1.61; non-reading age adjusted SMD
      0.51, 95%CI 0.36-0.66). CONCLUSION: AV interventions, especially those adjusted
      for participant reading age, improve immediate information recall for IC.
      Practice implications Wider use of AV aids is justified when obtaining IC in
      clinical practice.

PMID- 24041713
TI  - Context factors in consultations of general practitioner trainees and their
      impact on communication assessment in the authentic setting.
AB  - OBJECTIVE: Acquiring adequate communication skills is an essential part of
      general practice (GP) specialty training. In assessing trainee proficiency, the
      context in which trainees communicate is usually not taken into account. The
      present paper aims to explore what context factors can be found in regular GP
      trainee consultations and how these influence their communication performance.
      METHODS: In a randomly selected sample of 44 videotaped, real-life GP trainee
      consultations, we searched for context factors previously identified in GP
      consultations and explored how trainee ratings change if context factors are
      taken into account. Trainee performance was rated twice using the MAAS-Global,
      first without and then with incorporating context factors. Item score differences
      were calculated using a paired samples t-test and effect sizes were computed.
      RESULTS: All previously identified context factors were again observed in GP
      trainee consultations. In communication assessment scores, we found a significant
      difference in 5 out of 13 MAAS-Global items, mostly in a positive direction. The
      effect size was moderate (0.57). CONCLUSIONS: GP trainee communication is
      influenced by contextual factors; they seem to adapt to context in a professional
      way. PRACTICE IMPLICATIONS: GP specialty training needs to focus on a context
      specific application of communication skills. Communication raters need to be
      taught how to incorporate context factors into their assessments.

PMID- 24041714
TI  - Computational analysis of molt-inhibiting hormone from selected crustaceans.
AB  - Molt-inhibiting hormone (MIH) is a principal endocrine hormone regulating the
      growth in crustaceans. In total, nine MIH peptide sequences representing members
      of the family Penaeidae (Penaeus monodon, Litopenaeus vannamei, Marsupenaeus
      japonicus), Portunidae (Portunus trituberculatus, Charybdis japonica, Charybdis
      feriata), Cambaridae (Procambarus bouvieri), Parastacidae (Cherax
      quadricarinatus) and Varunidae (Eriocheir sinensis) were selected for our study.
      In order to develop a structure based phylogeny, predict functionally important
      regions and to define stability changes upon single site mutations, the 3D
      structure of MIH for the crustaceans were built by using homology modeling based
      on the known structure of MIH from M. japonicus (1J0T). Structure based phylogeny
      showed a close relationship between P. bouvieri and C. japonica. ConSurf server
      analysis showed that the residues Cys(8), Arg(15), Cys(25), Asp(27), Cys(28),
      Asn(30), Arg(33), Cys(41), Cys(45), Phe(51), and Cys(54) may be functionally
      significant among the MIH of crustaceans. Single amino acid substitutions 'Y' and
      'G' at the positions 71 and 72 of the MIH C-terminal region showed an alteration
      in the stability indicating that a change in this region may alter the function
      of MIH. In conclusion, we proposed a computational approach to analyze the
      structure, phylogeny and stability of MIH from crustaceans. 

PMID- 24041715
TI  - Analysis of gene expression in Homarus americanus larvae exposed to sublethal
      concentrations of endosulfan during metamorphosis.
AB  - Agricultural pesticide runoff has been suspected as the cause of numerous fish
      kills in rivers throughout Prince Edward Island but the impact on the surrounding
      marine environment is unknown. Endosulfan, an organochlorine pesticide, is a
      potent neurotoxin and molt inhibitor used to combat the Colorado potato beetle
      however it has the potential to affect non-target organisms including the
      American lobster (Homarus americanus). Metamorphosis is a critical stage of
      development and the effects of contaminant exposure during this time are largely
      unknown in lobster. A 14day endosulfan exposure was performed to identify the
      effects on survival, development and gene expression in lobster larvae during
      metamorphosis; all of which were predicted to be negatively impacted. The higher
      endosulfan concentrations resulted in greater mortality and a significant
      increase in the number of days required to reach metamorphosis in surviving
      animals. A custom made H. americanus microarray was used for monitoring the
      changes in expression of 14,592 genes at the termination of the exposure. Genes
      with >1.5 fold change and identified as being significant at p<0.05 using one-way
      ANOVA were selected for further analysis. A total of 707 genes were identified as
      being significantly differentiated, however with only ~40% annotation of the
      array, the majority of these genes were unknown. Annotated genes of interest were
      involved in many processes: development, metabolism, immunity and oxidative
      stress response and gene regulation. Nine genes of interest (histone H1,
      farnesoic acid O-methyltransferase, cuticle protein, glutathione S-transferase,
      thioredoxin, NADH dehydrogenase, ecdysone nuclear receptor Fushi tarazu F1 (FTZ
      F1), ferritin and ecdysone inducible protein E75 (EIP-E75)) were selected for RT
      qPCR validation of the microarray results. The RT-qPCR method was more sensitive
      than the microarray yet detected similar expression patterns. The two highest
      endosulfan concentrations resulted in increased mortalities, developmental delays
      in reaching metamorphosis and significant changes in gene expression. This
      research provides a foundation for using microarray gene expression profiles as
      screening tools for exploring the impact of environmental contaminants on
      lobster. 

PMID- 24041716
TI  - Study of symptom dimensions and clinical characteristics in Chinese patients with
      OCD.
AB  - BACKGROUND: The current study explored the main symptom dimensions and clinical
      characteristics of obsessive-compulsive disorder (OCD) in Chinese patients.
      METHODS: Obsessive-compulsive (OC) symptoms of participants (N=512) were assessed
      through the Yale-Brown Obsessive Compulsive Scale Checklist (YBOCS-CL).
      Exploratory category-level and item-level factor analyses were performed.
      Regression analysis was carried out to study the relationships between clinical
      characteristics in our sample and the symptom dimensions obtained. Relationships
      among the clinical characteristics were explored using the chi-square test.
      RESULTS: We found five symptom dimensions in the category-level analysis and six
      similar symptom dimensions in the item-level analysis. Moreover, the factors
      identified in our study overlapped with the results of prior studies. Association
      between gender and the symptom dimension of 'contamination/cleaning' was
      observed, with females showing more significant association with this dimension
      than males. Age of onset was associated with the symptom dimension of
      'symmetry/arranging/repeating/counting', with the early-onset group more actively
      associated with this dimension than the late-onset group. Early-onset patients
      with OCD were more likely to be male and show tic comorbidity. LIMITATIONS: Data
      from only one site do not represent the full range of Chinese OCD patients.
      Furthermore, past symptoms may show memory bias. Inherent problems in the YBOCS
      CL have also been identified. CONCLUSION: Symptoms in Chinese OCD patients are
      multidimensional. The main components of symptom dimensions of OCD patients show
      similarity or consistency among different regions and sociocultural backgrounds.
      The pathogenic mechanism of OCD may show potential distinctions.

PMID- 24041717
TI  - Is the combination of a mood stabilizer plus an antipsychotic more effective than
      mono-therapies in long-term treatment of bipolar disorder? A systematic review.
AB  - BACKGROUND: Bipolar Disorder (BD) long-term treatment is aimed to prevent
      relapses associated with worsening cognitive impairment and chronicity. Available
      mood stabilizers, including lithium, fail to prevent relapses in about 40% of
      bipolar patients. Purpose of the present paper is to review the available data
      about the efficacy and tolerability of mood stabilizer plus antipsychotic
      combined treatments. METHOD: A research in the main database sources has been
      conducted to obtain an overview about the efficacy and tolerability of the
      combination of a mood stabilizer plus an antipsychotic in the long-term treatment
      of BD. Papers with different methodologies but having relapse prevention as main
      outcome have been included. RESULTS: Despite the heterogeneity of studies in
      terms of methodology, almost all papers reported a major efficacy of combined
      treatments respect to mood stabilizer mono-therapies but lower tolerability. The
      antipsychotic that presents more evidence of efficacy in combination with mood
      stabilizers is quetiapine. DISCUSSION: Combined treatments can be a valid option
      to improve relapse prevention in BD. However, the higher risk for side effects
      has to be taken into account and specific combinations should be preferred
      according to patients' medical comorbidity.

PMID- 24041718
TI  - 1,25-Dihydroxyvitamin D3 induced histone profiles guide discovery of VDR action
      sites.
AB  - The chromatin environment dictates activity throughout the genome. Post
      translational modification of the N-terminal tails of histone proteins allow
      nucleosomes to shift, the chromatin to relax and genes to become activated.
      Histone modification events and markers will change in response to environmental
      stimuli; therefore they present a method for identification of sites of
      transcription factor activity. 1,25-Dihydroxyvitamin D3 induces the vitamin D
      receptor (VDR) to bind to DNA and activate transcription. These actions alter the
      chromatin environment and can be detected by increases or decreases in the
      histone modifications. In fact, in genomic loci with multiple enhancers,
      selective modulation of those enhancers after vitamin D3 stimulation can be
      readily detected by histone modifications. We provide an example of these actions
      on the Mmp13 gene locus where VDR binds selectively to an enhancer 10kb upstream
      of the transcriptional start site. This binding event is accompanied by an
      enhancer-selective increase in histone 3 lysine 9 acetylation (H3K9Ac). ChIP-seq
      analysis of histone modifications requires less genomic material than
      transcription factor ChIP-seq, thus proving advantageous to in vivo assays with
      limited cellular material. Therefore, histone modification activity alone may be
      used as a guide for discovering sites of VDR action for further biochemical
      analysis. This article is part of a Special Issue entitled '16th Vitamin D
      Workshop'. 

PMID- 24041720
TI  - Incidental Findings With Cross Calibration of the GE Prodigy and iDXA
      Densitometers.

PMID- 24041719
TI  - The immune system in menopause: pros and cons of hormone therapy.
AB  - With aging, a general decline in immune function is observed leading to immune
      senescence. Several of these changes are gender specific affecting postmenopausal
      women. Menopause is a normal part of a woman's lifecycle and consists of a series
      of body changes that can last from one to ten years. It is known that loss of sex
      hormones due to aging results in a reduction of immune functions. However, there
      remains a major gap in our understanding regarding the loss of immune functions
      particularly in the female reproductive tract (FRT) following menopause and the
      role of menopausal hormone therapy (MHT) in protecting against immune senescence.
      The current review presents an overview of changes in the immune system due to
      aging, focusing on genital tract immunity in menopausal women and the risks and
      benefits of using MHT. This article is part of a Special Issue entitled
      'Menopause'. 

PMID- 24041721
TI  - Predictors of HPV vaccination uptake: a longitudinal study among parents.
AB  - To assess among parents longitudinal predictors of human papillomavirus (HPV)
      vaccination uptake for their daughters, random samples of parents were identified
      via municipal services and sent baseline questionnaires in June 2009 and follow
      up questionnaires in November 2011 after their uptake decision. Hierarchical
      logistic regression analysis was used to assess whether demographic
      characteristics, and affective and social cognitive factors, predicted uptake at
      follow-up. Response rates of the baseline and follow-up questionnaire were 29.8%
      (1762/5918) and 74.3% (793/1067), respectively. Uptake was predicted by a later
      (2011) versus earlier (2010) decision about uptake as HPV vaccination
      implementation [odds ratio (OR) 2.48; 95% confidence interval (CI) 1.11-5.52],
      anticipated regret about no uptake (OR 1.43; 95% CI 1.08-1.89) and intention (OR
      2.61; 95% CI 1.47-4.61). There was an interaction between ambivalence and
      attitude (OR 1.68; 95% CI 1.14-2.47); parents with a positive attitude and a high
      ambivalence toward vaccination were more likely to have their daughter vaccinated
      than parents with a positive attitude and a low ambivalence. An informed choice
      about uptake (5/7 correct items) was made by 44%. In conclusion, uptake was
      predicted by intention, a later (2011) versus earlier (2010) decision and by
      anticipated regret about no uptake. Decisions regarding new vaccines are
      difficult to make, we recommend a well-balanced implementation process. 

PMID- 24041723
TI  - Voluntary timing of food intake increases weight gain and reduces basal plasma
      cortisol levels in common carp (Cyprinus carpio L.).
AB  - We investigated the effect of timing of food intake on growth in common carp
      (Cyprinus carpio L.). Juvenile carp were demand-fed for 22 days using a
      computerized pendulum feeder that registered meal requests. Controls were pair
      fed at 10:00 h, both groups were kept at 12L:12D (lights on at 06:30 h). Demand
      fed fish displayed highest food intake at 22:00 h, and the lowest at 10:00. After
      22 days, demand-fed fish had grown by 20% of their initial body weight, compared
      to 4% of the pair-fed control. Plasma cortisol levels in demand-fed fish were
      remarkably low and stable, whereas in the control group levels had increased 60
      fold at 10:00 h compared to 22:00 h. Hepatic mRNA expression of leptin-a1 and
      leptin-a2 also differed markedly between groups and time points, with leptin-a2
      expression being lowest in the demand-fed group at the time point of lowest food
      intake. We conclude that timing of food intake is an important determinant of
      endocrine status, growth and welfare.

PMID- 24041722
TI  - Beverages contribute extra calories to meals and daily energy intake in
      overweight and obese women.
AB  - Caloric beverages may promote obesity by yielding energy without producing
      satiety, but prior laboratory and intervention studies are inconclusive. This
      study examined whether the diets of free-living overweight and obese women show
      evidence that calories from beverages are offset by reductions in solid food
      within individual eating occasions and across entire days. Eighty-two women
      weighed and recorded all consumed foods and beverages for seven days. Beverages
      were coded as high-calorie (>= 0.165 kcal/g) or low-calorie (<0.165 kcal/g), and
      total energy intake and energy intake from solid food were calculated for each
      eating occasion and day. In covariate-adjusted models, energy intake from solid
      food did not differ between eating occasions that included high-calorie or low
      calorie beverages and those with no reported beverage. Energy intake from solid
      food was also unrelated to the number of high-calorie or low-calorie beverages
      consumed per day. On average, eating occasions that included a high-calorie
      beverage were 169 kcal higher in total energy than those with no reported
      beverage, and 195 kcal higher in total energy than those that included a low
      calorie beverage. Each high-calorie beverage consumed per day contributed an
      additional 147 kcal to women's daily energy intake, whereas low-calorie beverage
      intake was unrelated to daily energy intake. Beverages contributed to total
      energy intake in a near-additive fashion among free-living overweight and obese
      women, suggesting a need to develop more effective interventions to reduce
      caloric beverage intake in the context of weight management, and to potentially
      reexamine dietary guidelines.

PMID- 24041724
TI  - Influence of cross-fostering on preference for calcium chloride in C57BL/6J and
      PWK/PhJ mice.
AB  - We investigated whether maternal influences during the suckling period alter the
      avidity for calcium, using as models mice from the calcium-preferring PWK/PhJ
      strain and the calcium-avoiding C57BL/6J strain. We found that milk collected
      from PWK/PhJ dams had higher calcium concentrations than did milk collected from
      C57BL/6J dams. Despite this, cross-strain fostering had no effect on adult
      calcium preferences relative to mice of the same strain that were within-strain
      fostered or not fostered. Our results indicate that calcium avoidance by C57BL/6J
      mice and acceptance by PWK/PhJ mice are unaffected by maternal environment during
      the suckling period. 

PMID- 24041725
TI  - Timing and variability of postpartum sleep in relation to daytime performance.
AB  - Postpartum women have highly disturbed sleep, also known as sleep fragmentation.
      Fragmentation extends their total sleep period, also disrupting sleep timing. A
      stable and earlier sleep period among non-postpartum populations is related to
      better performance, physical health, and mental health. However, sleep timing has
      not been examined among postpartum women who are also vulnerable to daytime
      impairment. The study objective was to examine how the timing and regularity of
      sleep during the early postpartum period are related to daytime functioning
      across postpartum weeks 2-13. In this field-based study, 71 primiparous women
      wore an actigraph, a small wrist-worn device that monitors sleep and sleep
      timing, for the 12-week study period. Mothers self-administered a 5-min
      psychomotor vigilance test (PVT) each morning to evaluate the number of >500ms
      response lapses. They also completed a Morningness-Eveningness scale at the
      beginning of the study to identify chronotype. After controlling for maternal
      age, earlier sleep timing was associated with significantly fewer PVT lapses at
      postpartum weeks 9,12; a more stable sleep midpoint was associated with
      significantly fewer PVT lapses at postpartum weeks 2,5-13. Earlier sleep
      midpoints were related to more stable sleep midpoints at postpartum week 2 and a
      morning-type chronotype. An earlier sleep midpoint was also associated with a
      reduced slope of worsening PVT lapses across weeks. Across the first 12
      postpartum weeks, women with earlier or more stable sleep periods had less
      daytime impairment than women with later or more variable sleep midpoints.
      Postpartum women with earlier sleep midpoints also showed less severe decrements
      in performance across time, which has been attributed to cumulative impacts of
      sleep disturbance. These data suggest that the sleep period, in addition to sleep
      duration and fragmentation, should be more closely examined, particularly among
      vulnerable women, as it may affect the neurobehavioral performance of new
      mothers. 

PMID- 24041727
TI  - SRHC has now received its first five-year impact factor.

PMID- 24041726
TI  - National Consensus on the Diagnosis, Risk Stratification and Treatment of
      Patients with Pulmonary Embolism. Spanish Society of Pneumology and Thoracic
      Surgery (SEPAR). Society Espanola Internal Medicine (SEMI). Spanish Society of
      Thrombosis and Haemostasis (SETH). Spanish Society of Cardiology (ESC). Spanish
      Society of Medicine Accident and Emergency (SEMES). Spanish Society of Angiology
      and Surgery Vascular (SEACV).

PMID- 24041728
TI  - Burnout in Swedish midwives.
AB  - OBJECTIVE: In many countries midwives tend to leave their profession. Factors
      associated with workforce attrition include high workload, stress, poor
      management and a lack of promotional opportunities. The aim of the study was to
      investigate Swedish midwives' levels of burnout and their attitudes towards
      leaving the profession. METHOD: A random sample of 1000 midwives who are members
      of the Swedish Midwifery Association were sent a questionnaire. Burnout was
      measured using the Copenhagen Burnout Inventory. In addition the midwives were
      asked if they had experienced any situation that made them consider leaving their
      work and to give a comment about the reason. RESULTS: 475 of 978 Eligible
      midwives (48.6%) returned the questionnaire. The Cronbach alpha values ranged
      from 0.81 to 0.93 for the burnout subscales. One hundred and eighty four (39.5%)
      scored high in the subscale Personal burnout, while Work burnout and Client
      burnout was around 15%. The strongest associations between Burnout and midwives'
      characteristics were age <40, work and work experience <10 years. One in three
      midwives had considered leaving the profession. Lack of staff and resources and a
      stressful work environment was associated with all three subscales of midwives'
      burnout. Other important explanatory variables were conflict with work mates
      and/or mangers and worries about the future and own health. CONCLUSION: More than
      one third of the midwives included in this survey reported some kind of burnout.
      Paying attention to midwives work is important in order to maintain a healthy,
      motivated midwifery workforce that will continue serving women and their
      families.

PMID- 24041729
TI  - Perceptions and experiences of female genital mutilation after immigration to
      Sweden: an explorative study.
AB  - AIM: The aim of this study is to explore how women from part of the world where
      female genital mutilation (FGM) is normative perceive and experience FGM after
      immigrating to Sweden. METHOD: Interviews were conducted with eight women from
      Djibouti, Eritrea, Ethiopia and Somalia. The data were analyzed using qualitative
      content analysis. RESULTS: The women's feelings were ambivalent: though they
      opposed FGM, on the one hand, because of its negative effects on health, they
      acknowledged the practice's positive cultural aspects on the other hand. The
      themes that emerged from the interviews are the role of FGM in ensuring virginity
      and protecting a family's honor, its role in avoiding shame and enhancing purity,
      social pressure experienced after immigration, an understanding of FGM as a
      symbol of the country of origin, and support for changing the tradition.
      CONCLUSION: These findings indicate that women originating from communities where
      FGM is normative live in a context in which the practice is viewed as an
      important aspect of life even after immigration. More research concerning this
      complex and deeply rooted cultural issue is recommended.

PMID- 24041730
TI  - Somali women's use of maternity health services and the outcome of their
      pregnancies: a descriptive study comparing Somali immigrants with native-born
      Swedish women.
AB  - OBJECTIVES: To describe how Somali immigrant women in a Swedish county use the
      antenatal care and health services, their reported and observed health problems
      and the outcome of their pregnancies. STUDY DESIGN: Retrospective, case-control
      study, comparing data obtained from the records of antenatal and obstetric care
      for Somali born women with the same data for parity matched women born in Sweden
      giving birth between 2001 and 2009. MAIN OUTCOME MEASURES: Utilisation of
      antenatal health care (timing and number of visits), pregnancy complications
      (severe hyperemesis, anaemia, preeclampsia), mode of birth (normal vaginal,
      operative vaginal, caesarean), and infant outcomes (preterm birth, birth weight,
      and perinatal mortality). RESULTS: Compared to the 523 Swedish-born women the 262
      Somali women booked later and made less visits for antenatal care. They were more
      likely to have anaemia, severe hyperemesis and a few patients were found to have
      very serious health conditions. Emergency caesarean section (OR 1.90, CI 1.16
      3.10), especially before start of labour (OR 4.96, CI 1.73-14.22), high perinatal
      mortality with seven versus one perinatal deaths and small for date infants (OR
      2.95, CI 1.49-5.82) was also more prevalent. CONCLUSION: Pregnant Somali
      immigrant women still constitute a vulnerable group, which implicates that there
      is a missing link in the surveillance system that needs attention. There is an
      increased risk for intrauterine foetal death, small for date and low birth weight
      infants as well as serious maternal morbidity.

PMID- 24041731
TI  - Influence of NICU co-care facilities and skin-to-skin contact on maternal stress
      in mothers of preterm infants.
AB  - OBJECTIVE: To investigate the influence of co-care facilities and amount of skin
      to-skin contact during Neonatal Intensive Care Unit (NICU) stay on maternal
      stress in mothers of preterm infants at two months corrected age. METHODS: A
      prospective cohort study that involved 300 mothers of pre-term infants was
      conducted in four NICUs (two with co-care facilities and two with non co-care) in
      Sweden. Data on duration of skin-to-skin contact per day for all days admitted to
      the NICU were collected using self-reports. Maternal stress was measured by the
      Swedish Parental Stress Questionnaire (SPSQ) at two months of infant's corrected
      age. RESULTS: Mothers whose infants were cared for in a NICU with co-care
      facilities reported significantly lower levels of stress in the dimension of
      'incompetence' compared to mothers whose infants had been cared for in non co
      care NICUs. The amount of skin-to-skin experienced during the neonatal stay was
      not significantly associated with levels of maternal stress at two months
      corrected age. CONCLUSION: The finding that mothers who do not experience co-care
      facilities experience greater levels of stress in relation to feelings of
      incompetence is of concern. Improvements to NICU environments are needed to
      ensure that mother-infant dyads are not separated.

PMID- 24041732
TI  - Mothers' satisfaction with group antenatal care versus individual antenatal care-
      a clinical trial.
AB  - OBJECTIVE: The aim of this study was to compare women's satisfaction with group
      based antenatal care and standard care. DESIGN: A randomised control trial where
      midwives were randomized to perform either GBAC or standard care. Women were
      invited to evaluate the two models of care. Data was collected by two
      questionnaires, in early pregnancy and six months after birth. Crude and adjusted
      odds ratios with a 95% confidence interval were calculated by model of care.
      SETTINGS: Twelve antenatal clinics in Sweden between September 2008 and December
      2010. PARTICIPANTS: Women in various part of Sweden (n=700). FINDINGS: In total,
      8:16 variables in GBAC versus 9:16 in standard care were reported as deficient.
      Women in GBAC reported significantly less deficiencies with information about
      labour/birth OR 0.16 (0.10-0.27), breastfeeding OR 0.58 (0.37-0.90) and time
      following birth OR 0.61 (0.40-0.94). Engagement from the midwives OR 0.44 (0.25
      0.78) and being taken seriously OR 0.55 (0.31-0.98) were also found to be less
      deficient. Women in GBAC reported the highest level of deficiency with
      information about pregnancy OR 3.45 (2.03-5.85) but reported less deficiency with
      time to plan the birth OR 0.61 (0.39-0.96). In addition, women in GBAC more
      satisfied with care in supporting contact with other parents OR 3.86 (2.30-6.46)
      and felt more support to initiate breastfeeding OR 1.75 (1.02-2.88). CONCLUSIONS:
      Women in both models of care considered the care as deficient in more than half
      of all areas. Variables that differed between the two models favoured group based
      antenatal care.

PMID- 24041733
TI  - Group-based antenatal birth and parent preparation for improving birth outcomes
      and parenting resources: study protocol for a randomised trial.
AB  - OBJECTIVES: To examine the efficacy and cost-effectiveness of group based
      antenatal education for improving childbirth and parenting resources compared to
      auditorium based education. METHODS:  PARTICIPANTS: 2350 Danish pregnant women
      and their partners >=18 years old, recruited before 20+0 gestational weeks.
      Population-based individually randomised superiority trial with two parallel
      arms: Four sessions of birth and parent preparation in small groups (experimental
      group); two lectures in an auditorium (control group). Data is collected by (1)
      questionnaires at baseline (~18 weeks of gestation), 37 weeks of gestation, 9
      weeks-, 6 months-, and 1 year post-partum, (2) the hospital obstetric database,
      (3) national registers. PRIMARY OUTCOME: use of epidural analgesia. SECONDARY
      OUTCOMES: stress, parenting alliance; explorative outcomes: depressive symptoms,
      use of health care services, self-efficacy, well-being, family break-ups.
      Analyses will be intention-to-treat as well as per protocol. Process evaluation
      will be conducted using questionnaires and qualitative interviews. The
      incremental societal cost of the intervention will be computed and compared to
      the measured outcomes in a cost-effectiveness analysis. CONCLUSION: To the best
      of our knowledge this is the largest well-designed randomised trial of its kind
      to date. The trial will bring much-needed evidence for decision makers of the
      content and form of antenatal education.

PMID- 24041734
TI  - A patient's perspective of partnership in the treatment of multiple sclerosis: MS
      regimes--an orchestrated approach.
AB  - Having been an MS patient for over 15 years, I will give you a short picture of
      what I expect from my doctors with regard to an equilibrated doctor-patient
      relationship. Though such partnership also involves soft components like "My
      doctor's understanding of my personal situation" as well as "His understanding of
      my personality", this speech is limited to the hard components "Consideration of
      my individual course of disease" as well as "Provision of information and thereby
      educating me comprehensively". Also, I will point to some important legal aspects
      of such partnership and finally will give you some thoughts about some kind of
      "public partnership" in the internet. Consideration of individual course of
      disease: The doctor's choice of an appropriate treatment based on a careful and
      sound analysis and evaluation of the patient's personal individual course of
      disease may be impaired by strict compliance with guidelines. While guidelines
      may be helpful to ensure a broad high-level patient-centered care, they bear the
      risk that patients are treated according to standard programs just for the doctor
      to be on the safe side. Education of the patient: I will explain how I would like
      to be educated by my doctor in a perfect world. I will then elaborate that a
      comprehensive patient education may prevent loss of confidence as well as
      allegations like biased attitude of doctors, and may also positively influence
      cost pressure and adherence to treatments. Legal aspects of partnership: It is a
      physician's legal duty to educate his patients comprehensively. The right of the
      patients to be educated derives from their right of self-determination, which in
      turn arises directly from the patients' human dignity and personal rights. Forums
      and Medical Councils of MS-Societies: Internet communities do not seem to be too
      happy with their MS-Societies and experts. Statements of MS-Societies or their
      Medical Councils on hot topics have sometimes been slow. Via the forums, MS
      Societies may get an idea of the questions and problems MS patients have. They
      could inform the Medical Council accordingly, so that reactions regarding new
      developments or surprising trial results do not take too long.

PMID- 24041735
TI  - Concentrations of urinary 8-hydroxy-2'-deoxyguanosine and 8-isoprostane in women
      exposed to woodsmoke in a cookstove intervention study in San Marcos, Peru.
AB  - Nearly half of the world's population is exposed to household air pollution (HAP)
      due to long hours spent in close proximity to unvented cooking fires. The effect
      of woodsmoke exposure on oxidative stress was examined by investigating the
      association between woodsmoke exposure and biomarkers of DNA oxidation (8-hydroxy
      2'-deoxyguanosine [8-OHdG]) and lipid peroxidation (8-isoprostane) among control
      and intervention stove users. HAP exposure assessment was conducted within the
      framework of a community-randomized controlled trial of 51 communities in San
      Marcos Province, Cajamarca Region, Peru. The first morning urine voids after 48h
      HAP exposure assessment from a subset of 45 control and 39 intervention stove
      users were analyzed for 8-OHdG and 8-isoprostane. General linear models and
      correlation analyses were performed. Urinary oxidative stress biomarkers ranged
      from 11.2 to 2270.0MUg/g creatinine (median: 132.6MUg/g creatinine) for 8-OHdG
      and from 0.1 to 4.5MUg/g creatinine (median: 0.8MUg/g creatinine) for 8
      isoprostane among all study subjects (n=84). After controlling for the effects of
      traffic in the community and eating food exposed to fire among all subjects,
      cooking time was weakly, but positively associated with urinary 8-OHdG (r=0.29,
      p=0.01, n=80). Subjects' real-time personal CO exposures were negatively
      associated with 8-OHdG, particularly the maximum 30-second CO exposure during the
      sampling period (r=-0.32, p=0.001, n=73). 48h time integrated personal PM2.5 was
      negatively, but marginally associated with urinary 8-isoprostane (r=-0.21,
      p=0.09, n=69) after controlling for the effect of distance of homes to the road.
      Urinary 8-isoprostane levels reported in the available literature are comparable
      to results found in the current study. However there were relatively high levels
      of urinary 8-OHdG compared to data in the available literature for 8-OHdG
      excretion. Results suggest a sustained systemic oxidative stress among these
      Peruvian women chronically exposed to wood smoke. 

PMID- 24041737
TI  - Small bowel cleansing for capsule endoscopy in paediatric patients: a prospective
      randomized single-blind study.
AB  - BACKGROUND: Small bowel cleansing by capsule endoscopy has never been addressed
      in children. METHODS: Randomized controlled trial to evaluate the effect of five
      bowel preparation regimens on the mucosal visibility surface (as percentage of
      visualized surface area). Group A: a clear liquid diet for 12 h on the day
      before; Group B: high volume polyethylene glycol (50 mL/kg, up to 2Lt/die); Group
      C: low volume polyethylene glycol (25 mL/kg up to 1Lt/die); Group D: 20 mL (376
      mg) of oral simethicone; Group E: 25 mL/kg (up to 1Lt/die) of polyethylene glycol
      solution plus 20 mL (376 mg) of oral simethicone. RESULTS: Overall, 198 patients
      (53% male, median age 13 years) were enrolled. Preparation regimen visualization
      scores were 14.1 +/- 4.2, 18.9 +/- 5.1, 17.8 +/- 5.5, 14.9 +/- 4.8 and 20.9 +/-
      4.6 in groups A, B, C, D and E, respectively (P < 0.01). Positive findings were
      found in 172 cases (87%), but no significant differences were observed in the
      diagnostic yield and tolerability. Interobserver agreement, k = 0.89 (95% CI 0.83
      +/- 0.71). CONCLUSION: This is the first report in children that supports the use
      of 25 mL/kg (up to 1Lt/die) of polyethylene glycol solution plus 20 mL (376 mg)
      of oral simethicone as the preparation of choice for capsule endoscopy.

PMID- 24041736
TI  - Polyfluorinated compounds in dust from homes, offices, and vehicles as predictors
      of concentrations in office workers' serum.
AB  - We aimed to characterize levels of polyfluorinated compounds (PFCs) in indoor
      dust from offices, homes, and vehicles; to investigate factors that may affect
      PFC levels in dust; and to examine the associations between PFCs in dust and
      office workers' serum. Dust samples were collected in 2009 from offices, homes,
      and vehicles of 31 individuals in Boston, MA and analyzed for nineteen PFCs,
      including perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS),
      fluorotelomer alcohols (FTOHs), and sulfonamidoethanols (FOSEs). Serum was
      collected from each participant and analyzed for eight PFCs including PFOA and
      PFOS. Perfluorononanoate, PFOA, perfluoroheptanoate, perfluorohexanoate, PFOS and
      8:2 FTOH had detection frequencies >50% in dust from all three microenvironments.
      The highest geometric mean concentration in office dust was for 8:2 FTOH
      (309ng/g), while PFOS was highest in homes (26.9ng/g) and vehicles (15.8ng/g).
      Overall, offices had the highest PFC concentrations, particularly for longer
      chain carboxylic acids and FTOHs. Perfluorobutyrate was prevalent in homes and
      vehicles, but not offices. PFOA serum concentrations were not associated with PFC
      dust levels after adjusting for PFC concentrations in office air. Dust
      concentrations of most PFCs are higher in offices than in homes and vehicles.
      However, indoor dust may not be a significant source of exposure to PFCs for
      office workers. This finding suggests that our previously published observation
      of an association between FTOH concentrations in office air and PFOA
      concentrations in office workers was not due to confounding by PFCs in dust. 

PMID- 24041738
TI  - Photodynamic therapy with methyl-aminolevulinic acid for paucilesional mycosis
      fungoides: a prospective open study and review of the literature.
AB  - BACKGROUND: Publications reporting photodynamic therapy (PDT) in mycosis
      fungoides (MF) are rare, involve small samples, and are difficult to compare
      because of a lack of technical standardization. OBJECTIVE: We sought to assess
      PDT effectiveness and tolerability in early-stage MF using a strict reproducible
      procedure. METHODS: This was a prospective study conducted in Nantes University
      Hospital, France, including patients older than 18 years with histologically
      proven MF (stage IA or IB). Methyl-aminolevulinic acid-PDT sessions were repeated
      monthly for 6 months. Clinical and histologic responses were assessed 1 month
      after the last session. Patient satisfaction was assessed by telephone survey.
      RESULTS: Twelve patients (with 29 lesions) were treated with PDT. An objective
      response in target lesions was obtained in 75% of patients. Response rates were
      similar between plaques and patches but higher in sun-protected compared with sun
      exposed areas (trend without reaching significance). During PDT, new lesions
      appeared in 5 of 12 patients in untreated areas. Most patients were highly
      satisfied and preferred PDT to the topical chemotherapy previously used.
      LIMITATIONS: PDT procedure criteria selection was partially arbitrary.
      CONCLUSIONS: In early-stage MF, PDT is effective and appreciated (especially when
      compared with conventional topical chemotherapy). Unilesional and paucilesional
      forms and lesions in sun-protected areas are to be preferred.

PMID- 24041739
TI  - When all else fails: 21st century Amateur Radio as an emergency communications
      medium.
AB  - Twenty-first century demand for radio spectrum continues to increase with the
      explosive growth of wireless devices, but authorities reserve slices of the
      spectrum for licensed Amateur Radio operators, recognizing their value to the
      public, particularly with respect to providing emergency communications. Blood
      banking and transfusion medicine are among the specialties that should also
      recognize the value of Amateur Radio as an emergency communications medium,
      because blood collection, testing, processing, storage, and transfusion are life
      saving activities that in modern times can be separated by considerable distance.

PMID- 24041740
TI  - Hydrolysis of ibuprofenoyl-CoA and other 2-APA-CoA esters by human acyl-CoA
      thioesterases-1 and -2 and their possible role in the chiral inversion of
      profens.
AB  - Ibuprofen and related 2-arylpropanoic acid (2-APA) drugs are often given as a
      racemic mixture and the R-enantiomers undergo activation in vivo by metabolic
      chiral inversion. The chiral inversion pathway consists of conversion of the drug
      to the coenzyme A ester (by an acyl-CoA synthetase) followed by chiral inversion
      by alpha-methylacyl-CoA racemase (AMACR; P504S). The enzymes responsible for
      hydrolysis of the product S-2-APA-CoA ester to the active S-2-APA drug have not
      been identified. In this study, conversion of a variety of 2-APA-CoA esters by
      human acyl-CoA thioesterase-1 and -2 (ACOT-1 and -2) was investigated. Human
      recombinant ACOT-1 and -2 (ACOT-1 and -2) were both able to efficiently hydrolyse
      a variety of 2-APA-CoA substrates. Studies with the model substrates R- and S-2
      methylmyristoyl-CoA showed that both enzymes were able to efficiently hydrolyse
      both of the epimeric substrates with (2R)- and (2S)- methyl groups. ACOT-1 is
      located in the cytosol and is able to hydrolyse 2-APA-CoA esters exported from
      the mitochondria and peroxisomes for inhibition of cyclo-oxygenase-1 and -2 in
      the endoplasmic reticulum. It is a prime candidate to be the enzyme responsible
      for the pharmacological action of chiral inverted drugs. ACOT-2 activity may be
      important in 2-APA toxicity effects and for the regulation of mitochondrial free
      coenzyme A levels. These results support the idea that 2-APA drugs undergo chiral
      inversion via a common pathway. 

PMID- 24041741
TI  - Anti-atherogenic effects of statins: Impact on angiopoietin-2 release from
      endothelial cells.
AB  - Beyond lipid lowering, statins are supposed to exert pleiotropic effects
      positively influencing the progression of atherosclerotic lesions. The
      development of such lesions is associated with increased release of angiopoietin
      2 (Ang-2), an endothelial cell-specific protein growth factor stored in Weibel
      Palade bodies (WPBs). The aim of our study was to examine whether statin
      pretreatment influences the release of Ang-2 from endothelial cells. Stimulation
      of HUVECs and HMVECs with PMA, thrombin or histamine resulted in significant
      release of Ang-2, as evidenced by ELISA. Pretreatment with simvastatin and
      mevastatin suppressed this release to basal level, while pravastatin had no
      effect. Simvastatin itself increased nitric oxide (NO, EC number 1.14.13.39)
      synthesis, measured by Griess reaction. Combining the statin pretreatment with
      the eNOS inhibitor L-NNA as well as bypassing the HMG-CoA reductase (EC number:
      1.1.1.34) by adding mevalonic acid or geranyl pyrophosphate restored the
      exocytotic effect of PMA. Immunofluorescence microscopy showed that depletion of
      WPBs upon PMA stimulation ceased after pretreatment with simvastatin. This study
      demonstrates a potent suppressive effect of statins on the release of Ang-2 from
      endothelial cells. Regarding its harmful effects in the development of
      atherosclerotic lesions, our data provide further insight into the mechanisms of
      the anti-atherogenic potential of statins. 

PMID- 24041742
TI  - STLC-resistant cell lines as tools to classify chemically divergent Eg5 targeting
      agents according to their mode of action and target specificity.
AB  - Determining the mechanism of action of drugs and their target specificity in
      cells remains a major challenge. Here we describe the use of cell lines
      expressing two point mutations in the allosteric inhibitor binding pocket of the
      mitotic kinesin Eg5 (D130A, in the loop L5 region and L214A in helix alpha3),
      which following transfection, were selected for their ability to proliferate
      normally in the presence of STLC, a well known Eg5 inhibitor. The cell lines were
      used to discriminate the mechanism of action of other chemically distinct small
      molecule inhibitors of Eg5 that differ in their mode of action. The STLC
      resistant cells were capable of continuous proliferation in the presence of ATP
      uncompetitive inhibitors, such as K858 and dimethylenastron, but were still
      sensitive to ATP competitive inhibitors that are thought to bind to a distinct
      site on Eg5 than the allosteric binding pocket. The STLC resistant cell lines can
      therefore be used as a filter to distinguish Eg5 loop L5 binding drugs from drugs
      binding to other pockets without prior structural information. Additionally, the
      cells can be used to analyze whether inhibitors of Eg5 are specific to this
      potential drug target or whether they have additional targets in dividing cells. 

PMID- 24041743
TI  - OSU-A9, an indole-3-carbinol derivative, induces cytotoxicity in acute myeloid
      leukemia through reactive oxygen species-mediated apoptosis.
AB  - Indole-3-carbinol (I3C) is a broadly targeted phytochemical shown to prevent
      carcinogenesis in animal studies and to suppress the proliferation of cancer
      cells of human breast, colon, prostate, and endometrium. Here we demonstrate that
      OSU-A9, an I3C derivative with improved anticancer potency, induces cytotoxicity
      in acute myeloid leukemia (AML) cell lines (HL-60 and THP-1) and primary leukemia
      cells from AML patients in a dose-responsive manner. Normal human bone marrow
      cells were less sensitive to OSU-A9 than leukemia cells. OSU-A9 induces caspase
      activation, PARP cleavage, and autophagy but not autophagic cell death.
      Interestingly, pretreatment of AML cell lines and primary AML cells with N
      acetylcysteine or glutathione rescues them from apoptosis (and concomitant PARP
      cleavage) and Akt hypophosphorylation, implicating a key role of reactive oxygen
      species (ROS) in OSU-A9-related cytotoxicity. Importantly, the anticancer utility
      of OSU-A9 is extended in vivo as it, administered intraperitoneally, suppresses
      the growth of THP-1 xenograft tumors in athymic nude mice without obvious
      toxicity. This study shows that ROS-mediated apoptosis contributes to the
      anticancer activity of OSU-A9 in AML cell lines and primary AML cells, and thus
      should be considered in the future assessment of its translational value in AML
      therapy. 

PMID- 24041744
TI  - Learning and confirming with preclinical studies: modeling and simulation in the
      discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist.
AB  - The application of modeling and simulation techniques is increasingly common in
      the preclinical stages of the drug development process. GDC-0917 [(S)-1-((S)-2
      cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)-N-(2-(oxazol-2-yl)-4
      phenylthiazol-5-yl)pyrrolidine-2-carboxamide] is a potent second-generation
      antagonist of inhibitor of apoptosis (IAP) proteins that is being developed for
      the treatment of various cancers. GDC-0917 has low to moderate clearance in the
      mouse (12.0 ml/min/kg), rat (27.0 ml/min/kg), and dog (15.3 ml/min/kg), and high
      clearance in the monkey (67.6 ml/min/kg). Accordingly, oral bioavailability was
      lowest in monkeys compared with other species. Based on our experience with a
      prototype molecule with similar structure, in vitro-in vivo extrapolation was
      used to predict a moderate clearance (11.5 ml/min/kg) in humans. The predicted
      human volume of distribution was estimated using simple allometry at 6.69 l/kg.
      Translational pharmacokinetic-pharmacodynamic (PK-PD) analysis using results from
      MDA-MB-231-X1.1 breast cancer xenograft studies and predicted human
      pharmacokinetics suggests that ED50 and ED90 targets can be achieved in humans
      using acceptable doses (72 mg and 660 mg, respectively) and under an acceptable
      time frame. The relationship between GDC-0917 concentrations and pharmacodynamic
      response (cIAP1 degradation) was characterized using an in vitro peripheral blood
      mononuclear cell immunoassay. Simulations of human GDC-0917 plasma concentration
      time profile and cIAP1 degradation at the 5-mg starting dose in the phase 1
      clinical trial agreed well with observations. This work shows the importance of
      leveraging information from prototype molecules and illustrates how modeling and
      simulation can be used to add value to preclinical studies in the early stages of
      the drug development process. 

PMID- 24041745
TI  - Reference values and factors associated with exhaled nitric oxide: U.S. youth and
      adults.
AB  - BACKGROUND: Normative values for fractional exhaled nitric oxide (FeNO) and the
      associated co-factors are important in understanding the role of FeNO as a
      biomarker in airway disease. The objective of this study is to establish
      reference FeNO values for youth and adult asymptomatic, lifetime nonsmokers in
      the United States, and to describe the factors affecting these levels. METHODS:
      Cross-sectional analyses of the National Health and Nutrition Examination Survey
      from 2007 to 2010. The analytic sample consisted of 4718 youth and adults, ages 6
      79 years, who were lifelong nonsmokers, and free of asthma, and other respiratory
      conditions and symptoms. Loge FeNO values were used as dependent variables to
      test associations of demographic and health related-covariates. Multivariable
      regression models were used to assess the independent effect and covariate
      adjusted contribution of the factors. RESULTS: The geometric mean FeNO level was
      8.3, 12.1, and 16.2 ppb for males 6-11, 12-19, and 20-79 years, and 8.4, 10.9,
      and 12.6 ppb for females in the corresponding age groups. Overall, FeNO levels
      increased with increasing age (p < 0.001), and height (p < 0.001). In all age
      groups, FeNO levels were positively associated with eosinophil counts, and with
      testing in the morning. Among youths 6-11 and 12-19 years, non-Hispanics whites
      had lower FeNO values than non-Hispanic blacks and Hispanic youths. No race
      ethnic difference in FeNO levels was evident for adults 20-79 years. Among
      adolescents and adults, FeNO levels were higher for males than for females,
      controlling for all other factors. CONCLUSIONS: These reference values and
      associated attributes in youths and adults are useful in evaluating the role of
      FeNO in airway diseases.

PMID- 24041746
TI  - Characteristics of a COPD population categorised using the GOLD framework by
      health status and exacerbations.
AB  - GOLD proposed a COPD assessment framework focussed on symptoms measured by the
      COPD Assessment TestTM (CAT) or the mMRC and on exacerbation risk based on poor
      lung function (FEV1 <50%) or a history of >=2 exacerbations in the previous year.
      This analysis examined the characteristics of COPD patients recruited from
      routine clinical settings and classified using the GOLD framework. 1041 European
      COPD patients (38.5% from primary care) from the Adelphi Respiratory Disease
      Specific Programme with information on CAT, mMRC, spirometry and exacerbation
      history in the previous year were analysed. Their mean age was 64.9 +/- 9.9 years
      and mean FEV1 was 62.5 +/- 17.8% predicted; 80% were in GOLD 2 spirometric grade
      or milder. CAT and mMRC cut points identified different groups of patients; using
      CAT, the composition was: Group A 9.3%, Group B 48.5%, Group C 0.7% and Group D
      41.5%. 80% were classified as high risk based on exacerbation history and 25% of
      patients in a low risk category (GOLD A and B) had 1 exacerbation in the previous
      year. The incidence of diabetes, hypertension and hyperlipidaemia rose with
      worsening GOLD group (all p < 0.0001); diabetes GOLD A 4%, GOLD B 16%, GOLD D
      29%; hypertension GOLD A 38%, GOLD B 55%, GOLD D 65%; hyperlipidaemia GOLD A 13%,
      GOLD B 30%, GOLD D 37%. In patients seen in routine clinical settings, 25% of
      GOLD low risk patients had one exacerbation per year and the incidence of cardio
      vascular and metabolic diseases increases with worsening GOLD group. 

PMID- 24041747
TI  - 90-Day subchronic toxicity study of sodium molybdate dihydrate in rats.
AB  - This study investigated the subchronic toxicity of molybdenum (Mo) in Sprague
      Dawley rats given sodium molybdate dihydrate in the diet for 90days at dose
      levels of 0, 5, 17 or 60mgMo/kgbw/day. The study complied with OECD Test
      Guideline (TG) 408, with additional examination of estrus cycles and sperm count,
      motility, and morphology from OECD TG 416. The overall no-observed-adverse-effect
      level was 17mgMo/kgbw/day, based on effects on body weight, body weight gain,
      food conversion efficiency and renal histopathology (females only) at
      60mgMo/kgbw/day. No treatment-related adverse effects on reproductive organ
      weights or histopathology, estrus cycles or sperm parameters were observed at any
      dose level. No adverse effects were observed in the high dose animals after the
      60-day recovery period, with the exception that male rats did not fully recover
      from reduced body weight. Serum blood, liver and kidney samples were analyzed for
      molybdenum, copper, zinc, manganese, iron, cobalt and selenium; high levels of
      molybdenum and copper were found in the serum, blood, liver and kidneys of rats
      treated with 60mgMo/kgbw/day. In conclusion, the LOAEL and NOAEL for molybdenum
      were determined to be 60 and 17mgMo/kgbw/day, respectively. 

PMID- 24041748
TI  - A computer-based feedback only intervention with and without a moderation skills
      component.
AB  - Research on the efficacy of computer-delivered feedback-only interventions (FOIs)
      for college alcohol misuse has been mixed. Limitations to these FOIs include
      participant engagement and variation in the use of a moderation skills component.
      The current investigation sought to address these limitations using a novel
      computer-delivered FOI, the Drinkers Assessment and Feedback Tool for College
      Students (DrAFT-CS). Heavy drinking college students (N=176) were randomly
      assigned to DrAFT-CS, DrAFT-CS plus moderation skills (DrAFT-CS+), moderation
      skills only (MSO), or assessment only (AO) group, and were assessed at 1-month
      follow-up (N=157). Participants in the DrAFT-CS and DrAFT-CS+groups reported
      significantly lower estimated blood alcohol concentrations (eBACs) on typical
      heaviest drinking day than participants in the AO group. The data also supported
      the incorporation of a moderation skills component within FOIs, such that
      participants in DrAFT-CS+group reported significantly fewer drinks per week and
      drinks per heaviest drinking occasion than participants in the AO group. 

PMID- 24041749
TI  - Technology-based interventions for the treatment and recovery management of
      substance use disorders: a JSAT special issue.
AB  - A growing line of research has highlighted the promising role that interactive
      web and mobile technologies may play in improving the effectiveness, cost
      effectiveness, and reach of efforts to assess, prevent, treat, and support the
      recovery management of substance use disorders and other risk behavior.
      Manuscripts in this special issue of the Journal of Substance Abuse Treatment
      focus on the application of technology to the delivery of interventions for the
      treatment and recovery management of substance use disorders. These manuscripts
      are intended to highlight the diversity and current state of the science of
      empirically-supported innovations in this area of intervention delivery. The
      included manuscripts range from experimental evaluations of a variety of types of
      technology-based interventions (brief interventions, behavior therapy, medication
      adherence tools, and HIV prevention interventions) and technology platforms
      (mobile, Web, videoconferencing, and telephone-based interactive voice response),
      for an array of populations (adults, adolescents, criminal justice populations,
      and post-partum women), in a number of different settings (addiction specialty
      treatment programs, schools, emergency rooms, and criminal justice settings).
      They additionally reflect a variety of experimental research designs, including
      those focused on the design, development, and clinical evaluation of these
      technology-based therapeutic tools, as well as research focused on models for
      their successful implementation and sustained use. 

PMID- 24041750
TI  - Depressive symptoms and sleep: a population-based polysomnographic study.
AB  - The goals of the present study were to determine the prevalence of depression in
      the adult population of Sao Paulo, Brazil and to explore the relationship among
      sociodemographic, physical and psychological factors, sleep-related symptoms and
      polysomnography parameters. Participants of a cross-sectional study (N = 1101)
      were administered questionnaires and submitted to polysomnography. A score > 20
      in the Beck Depression Inventory was used to describe depression. Results
      revealed that the prevalence of depression was 10.9%. Estimates were higher in
      women and were significantly higher among housewives, non-workers and individuals
      with lower education and income. A combination of sleep-related symptoms and
      impaired quality of life was 2.5 times more frequent among depressed than non
      depressed. Co-morbid insomnia and anxiety were positively associated to
      depressive symptomatology. There were no alterations in the polysomnography
      parameters, in either group. The occurrence of sleep apnea with values on the
      apnea-hypopnea index >= 5 was similar and frequent in both groups (around 30%).
      The findings suggest that depressive symptoms were associated with low education,
      low income, severe comorbid symptomatology, and impaired quality of life.
      Considering the high prevalence of sleep apnea, these results point to potential
      social and financial burdens associated with the depressive symptomatology and
      various sleep diagnoses.

PMID- 24041751
TI  - Oxidative stress in schizophrenia patients treated with long-acting haloperidol
      decanoate.
AB  - In this study the role of oxidative stress in schizophrenia was investigated by
      evaluating the relationship of oxidative stress markers with neurochemistry,
      psychopathology, and extrapyramidal symptoms. Antioxidant activity of superoxide
      dismutase, catalase, glutathione peroxidase, glutathione reductase, and
      concentrations of malondialdehyde, protein carbonyls, nitrite, nitrate,
      glutathione, dopamine, noradrenaline, adrenaline, and serotonin were measured in
      52 outpatients with DSM-IV diagnosis of schizophrenia treated with haloperidol
      decanoate. Psychopathology and extrapyramidal symptoms were assessed by positive
      and negative syndrome scale, global assessment of functioning, abnormal
      involuntary movement scale, Simpson Angus scale, and Barnes akathisia rating
      scale. Haloperidol dose was positively correlated with plasma protein carbonyls.
      Longer duration of illness was associated with decreased levels of glutathione
      peroxidase. Increased activity of superoxide dismutase was associated with
      increased levels of catalase, glutathione peroxidase, glutathione reductase and
      reduced glutathione, and decreased concentration of malondialdehyde, indicating
      joint action of various antioxidative systems. Increased levels of nitrite and
      noradrenaline were associated with decreased level of malondialdehyde. Akathisia
      was greater in patients with decreased catalase activity, indicating involvement
      of impaired antioxidant defense in developing extrapyramidal symptoms. These
      results confirm the hypothesis that oxidative stress is involved in
      pathophysiology of schizophrenia and severity of extrapyramidal symptoms. 

PMID- 24041752
TI  - Neurocognitive impairments and quality of life in unemployed patients with
      remitted major depressive disorder.
AB  - Quality of life (QOL) has been reported to be impaired in patients with major
      depressive disorder (MDD), even after remission according to symptom rating
      scales. Although a relationship between QOL and neurocognitive dysfunction has
      been reported during depressive episodes, little is known about this relationship
      in remitted MDD patients. The aim of the present study was to investigate the
      relationship between QOL and neurocognitive dysfunction in patients with remitted
      MDD while controlling for confounding factors. Forty-three remitted MDD patients
      were assessed with neuropsychological tests and QOL, which was measured by a
      short-form 36-item health survey. The neurocognitive performances of the patients
      were compared with those of 43 healthy controls. We next evaluated the
      relationships between neurocognitive impairments, clinical factors, and QOL.
      Remitted MDD patients had poorer neurocognitive performances than healthy
      controls for psychomotor speed, attention, and verbal memory. Residual depressive
      symptoms were strongly associated with QOL. Delayed verbal recall was associated
      with general health perceptions, which are part of the QOL assessment, even after
      the effects of the residual depressive symptoms were considered. The results may
      indicate that clinicians should try to detect neurocognitive dysfunctions that
      may interfere with QOL using neurocognitive assessments in their daily practice. 

PMID- 24041753
TI  - Uniaxial and biaxial mechanical characterization of a prosthetic mesh at
      different length scales.
AB  - This study is aimed at a comprehensive experimental analysis of the mechanical
      behavior of a prosthetic mesh considering different length scales. Uniaxial and
      biaxial protocols are developed to evaluate global mechanical phenomena of the
      dry mesh. Furthermore, procedures for local deformation analysis and evaluation
      of corresponding homogenized kinematic measures are described. The global
      mechanical response of the prosthetic mesh is characterized by anisotropy, a
      nonlinear force response, hysteresis and preconditioning effects. The local
      deformation analysis allows to identify mesh specific phenomena related to
      mechanisms at the unit cell level. The global and the local kinematic responses
      of the mesh are seen to be directly related to clinical observations and help to
      understand associated complications, such as wrinkle formation, dislocation or
      erosion. In that sense, this study contributes to the analysis of mechanical
      biocompatibility of mesh implants and proposes protocols for comprehensive mesh
      product descriptions. 

PMID- 24041754
TI  - A novel strategy to identify the critical conditions for growth-induced
      instabilities.
AB  - Geometric instabilities in living structures can be critical for healthy
      biological function, and abnormal buckling, folding, or wrinkling patterns are
      often important indicators of disease. Mathematical models typically attribute
      these instabilities to differential growth, and characterize them using the
      concept of fictitious configurations. This kinematic approach toward growth
      induced instabilities is based on the multiplicative decomposition of the total
      deformation gradient into a reversible elastic part and an irreversible growth
      part. While this generic concept is generally accepted and well established
      today, the critical conditions for the formation of growth-induced instabilities
      remain elusive and poorly understood. Here we propose a novel strategy for the
      stability analysis of growing structures motivated by the idea of replacing
      growth by prestress. Conceptually speaking, we kinematically map the stress-free
      grown configuration onto a prestressed initial configuration. This allows us to
      adopt a classical infinitesimal stability analysis to identify critical material
      parameter ranges beyond which growth-induced instabilities may occur. We
      illustrate the proposed concept by a series of numerical examples using the
      finite element method. Understanding the critical conditions for growth-induced
      instabilities may have immediate applications in plastic and reconstructive
      surgery, asthma, obstructive sleep apnoea, and brain development. 

PMID- 24041755
TI  - Mammalian-derived respiratory allergens - implications for diagnosis and therapy
      of individuals allergic to furry animals.
AB  - Furry animals cause respiratory allergies in a significant proportion of the
      population. A majority of all mammalian allergens are spread as airborne
      particles, and several have been detected in environments where furry animals are
      not normally kept. The repertoire of allergens from each source belongs to a
      restricted number of allergen families. Classification of allergen families is
      particularly important for the characterization of allergenicity and cross
      reactivity of allergens. In fact, major mammalian allergens are taken from only
      three protein families, i.e. the secretoglobin, lipocalin and kallikrein
      families. In particular, the lipocalin superfamily harbours major allergens in
      all important mammalian allergen sources, and cross-reactivity between lipocalin
      allergens may explain cross-species sensitization between mammals. The
      identification of single allergen components is of importance to improve
      diagnosis and therapy of allergic patients using component-resolved diagnostics
      and allergen-specific immunotherapy (ASIT) respectively. Major disadvantages with
      crude allergen extracts for these applications emphasize the benefits of careful
      characterization of individual allergens. Furthermore, detailed knowledge of the
      characteristics of an allergen is crucial to formulate attenuated allergy
      vaccines, e.g. hypoallergens. The diverse repertoires of individual allergens
      from different mammalian species influence the diagnostic potential and clinical
      efficacy of ASIT to furry animals. As such, detailed knowledge of individual
      allergens is essential for adequate clinical evaluation. This review compiles
      current knowledge of the allergen families of mammalian species, and discusses
      how this information may be used for improved diagnosis and therapy of
      individuals allergic to mammals. 

PMID- 24041756
TI  - Electrical percolation based biosensors.
AB  - A new approach to label free biosensing has been developed based on the principle
      of "electrical percolation". In electrical percolation, long-range electrical
      connectivity is formed in randomly oriented and distributed systems of discrete
      elements. By applying this principle to biological interactions, it is possible
      to measure biological components both directly and electronically. The main
      element for electrical percolation biosensor is the biological semiconductor
      (BSC) which is a multi-layer 3-D carbon nanotube-antibody network. In the BSC,
      molecular interactions, such as binding of antigens to the antibodies, disrupt
      the network continuity causing increased resistance of the network. BSCs can be
      fabricated by immobilizing conducting elements, such as pre-functionalized single
      walled carbon nanotubes (SWNTs)-antibody complex, directly onto a substrate, such
      as a Poly(methyl methacrylate) (PMMA) surface (also known as plexi-glass or
      Acrylic). BSCs have been demonstrated for direct (label-free) electronic
      measurements of antibody-antigen binding using SWNTs. If the concentration of the
      SWNT network is slightly above the electrical percolation threshold, then binding
      of a specific antigen to the pre-functionalized SWNT dramatically increases the
      electrical resistance due to changes in the tunneling between the SWNTs. Using
      anti-staphylococcal enterotoxin B (SEB) IgG as a "gate" and SEB as an "actuator",
      it was demonstrated that the BSC was able to detect SEB at concentrations of 1
      ng/ml. Based on this concept, an automated configuration for BSCs is described
      here that enables real time continuous detection. The new BSC configuration may
      permit assembly of multiple sensors on the same chip to create "biological
      central processing units (CPUs)" with multiple biological elements, capable of
      processing and sorting out information on multiple analytes simultaneously.

PMID- 24041757
TI  - Growth hormone replacement normalizes impaired fibrinolysis: new insights into
      endothelial dysfunction in patients with hypopituitarism and growth hormone
      deficiency.
AB  - BACKGROUND: Cardiovascular morbidity in adult patients with growth hormone
      deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular
      risk factors leading to endothelial dysfunction and impaired fibrinolysis has
      also been reported and may account for progression to overt vascular changes in
      these patients. However, effect of long lasting GH replacement therapy on
      fibrinolytic capacity in GH deficient patients has not been investigated so far.
      OBJECTIVE: To investigate fibrinolysis before and after challenge with venous
      occlusion in GHD patients with hypopituitarism before and during one year of
      growth hormone replacement. DESIGN: Hospital based, interventional, prospective
      study. INVESTIGATED SUBJECTS: Twenty one patient with GHD and fourteen healthy
      control subjects matched for age, sex and body mass index (BMI). METHODS:
      Anthropometric, metabolic and fibrinolytic parameters were measured at the start
      and after three, six and twelve months of treatment with human recombinant GH.
      RESULTS: At baseline GHD patients had significantly impaired fibrinolysis
      compared to healthy persons. During treatment with GH, significant changes were
      observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4-13.5) to
      22.0(9.0-33.0) nmol/l after one month of treatment; p<0.01] and fibrinolysis.
      Improvement in fibrinolysis was mostly attributed to improvement of stimulated
      endothelial tissue plasminogen activator (t-PA) release in response to venous
      occlusion [from baseline 1.1(0.4-2.6) to 1.9(0.5-8.8) after one year of
      treatment; p<0.01]. CONCLUSION: Growth hormone replacement therapy has favorable
      effects on t-PA release from endothelium and net fibrinolytic capacity in GHD
      adults, which may contribute to decrease their risk of vascular complications.

PMID- 24041758
TI  - Protective effects of tocotrienols against lipid-induced nephropathy in
      experimental type-2 diabetic rats by modulation in TGF-beta expression.
AB  - Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered
      a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia
      and hyperglycemia act synergistically to induce renal injury. The present study
      was designed to investigate the protective effects of tocotrienols as tocotrienol
      rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against
      lipid induced nephropathy in type-2 diabetic rats and its probable molecular
      mechanism. Male Wistar rats (175-200 g) were divided into four groups. The first
      group served as diabetic control, while the second and third groups received PO
      TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post
      induction of diabetes. The fourth group comprised of age-matched rats that served
      as normal control. The effects of TRF on serum lipid profile, oxidative stress
      markers, expression of TGF-beta, fibronectin and collagen type IV were analyzed
      in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly
      improved glycemic status, serum lipid profile and renal function in type-2
      diabetic rats. In addition, TRF supplementation down-regulated the expression of
      TGF-beta, fibronectin and collagen type IV in the kidney of diabetic rats.
      Transforming growth factor-beta (TGF-beta) plays a critical role in progression
      of DN, but its modulation by tocotrienols in DN remains unexplored. TRF
      ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic,
      hypolipidemic and antioxidant activities as well as by modulation of TGF-beta to
      prevent increased expression of collagen type IV and fibrinogen. We finally
      propose a mechanism for the expression of molecular markers that are significant
      in the events leading to diabetic nephropathy and its modulation by
      tocotrienols/TRF.

PMID- 24041759
TI  - Mice, cows, dung beetles, shrews, and drunken humans triumph in 2013 Ig Nobel
      prize.

PMID- 24041760
TI  - NHS must publish more data and value staff more, outgoing chief says.

PMID- 24041762
TI  - Co-pyrolysis behaviors of saw dust and Shenfu coal in drop tube furnace and fixed
      bed reactor.
AB  - Co-pyrolysis behaviors of saw dust (SD) and Shenfu bituminous coal (SF) were
      studied in a drop tube furnace and a fixed bed reactor at different temperatures
      respectively. Six different biomass/coal ratios (B:C) were used. Compared the
      results with the calculated value obtained by the additional behavior, CO volume
      yields were lower while H2, CH4, CO2, volume yields were higher. Blend char
      yields had a good agreement with the calculated values, and their structures
      remained similar with SD and SF char's. Synergy effect occurred in gaseous phase,
      which was mainly caused by the secondary reactions. Compared the blend char
      yields in the drop tube furnace with those in the fixed bed reactor, the results
      showed the contacting way of biomass and coal particles had little influence on
      char yield in co-pyrolysis process. The reactivity index of blend char achieved
      the minimum at B:C=40:60 and the maximum at B:C=80:20. 

PMID- 24041763
TI  - Human chromosome 21 orthologous region on mouse chromosome 17 is a major
      determinant of Down syndrome-related developmental cognitive deficits.
AB  - Trisomy 21 (Down syndrome, DS) is the most common genetic cause of developmental
      cognitive deficits, and the so-called Down syndrome critical region (DSCR) has
      been proposed as a major determinant of this phenotype. The regions on human
      chromosome 21 (Hsa21) are syntenically conserved on mouse chromosome 10 (Mmu10),
      Mmu16 and Mmu17. DSCR is conserved between the Cbr1 and Fam3b genes on Mmu16.
      Ts65Dn mice carry three copies of ~100 Hsa21 gene orthologs on Mmu16 and
      exhibited impairments in the Morris water maze and hippocampal long-term
      potentiation (LTP). Converting the Cbr1-Fam3b region back to two copies in Ts65Dn
      mice rescued these phenotypes. In this study, we performed similar conversion of
      the Cbr1-Fam3b region in Dp(16)1Yey/+ mice that is triplicated for all ~115 Hsa21
      gene orthologs on Mmu16, which also resulted in the restoration of the wild-type
      phenotypes in the Morris water maze and hippocampal LTP. However, converting the
      Cbr1-Fam3b region back to two copies in a complete model,
      Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+, failed to yield the similar phenotypic
      restorations. But, surprisingly, converting both the Cbr1-Fam3b region and the
      Hsa21 orthologous region on Mmu17 back to two copies in the complete model did
      completely restore these phenotypes to the wild-type levels. Our results
      demonstrated that the Hsa21 orthologous region on Mmu17 is a major determinant of
      DS-related developmental cognitive deficits. Therefore, the inclusion of the
      three copies of this Hsa21 orthologous region in mouse models is necessary for
      unraveling the mechanism underlying DS-associated developmental cognitive
      deficits and for developing effective interventions for this clinical
      manifestation.

PMID- 24041764
TI  - Chordal cutting in ischemic mitral regurgitation: a propensity-matched study.
AB  - OBJECTIVE: The optimal surgical treatment of ischemic mitral regurgitation (MR)
      has not been well defined. Second-order chordal cutting (CC), in selected
      patients, can improve surgical outcomes. METHODS: From 2007 to 2011, 31 patients
      underwent CC for ischemic MR. The indication was the presence of increased
      tethering of the anterior leaflet, with a bending angle (BA) <145 degrees .
      Patients with same echocardiographic characteristics were identified and
      propensity matched for age, ejection fraction (EF), MR grade, diameters, and BA.
      Only patients with preoperative and follow-up echocardiograms were included and
      divided into 2 groups of 26 patients each, CC and no-CC. RESULTS: Preoperatively,
      in the CC and no-CC groups, the age was 61 +/- 9 and 62 +/- 10 years, EF was 31%
      +/- 5% and 29% +/- 8%, MR grade (0-4) was 3.6 +/- 0.6 and 3.3 +/- 0.8, and
      diastolic and systolic dimension was 56 +/- 7 and 43 +/- 8 mm and 57 +/- 11 and
      44 +/- 11 mm, respectively. The New York Heart Association class and BA was 2.7
      +/- 0.6 and 2.6 +/- 0.7 and 137 degrees  +/- 4 degrees  and 137 degrees  +/- 6
      degrees , respectively. All patients underwent overreductive annuloplasty. In the
      CC group, second-order chords were cut using aortotomy. After a mean of 33 +/- 15
      months, the MR grade was 0.6 +/- 0.6 and 1.1 +/- 0.8 (P = .014) and the EF was
      40% +/- 5% and 35% +/- 7% (P = .005) in the CC and no-CC groups, respectively.
      The corresponding diastolic and systolic diameters were 52 +/- 5 and 38 +/- 8 mm
      and 53 +/- 11 and 41 +/- 12 mm (P = NS). The modifications were significant only
      in the CC group (P = .022 and P = .029 for the diastolic and systolic dimensions,
      respectively). The corresponding New York Heart Association class decreased to
      1.1 +/- 0.3 and 1.5 +/- 0.6 (P = .004). The BA increased to 182 degrees  +/- 4
      degrees  in the CC (P < .001) and remained unchanged (137 degrees  +/- 6 degrees
      ) in the no-CC group. CONCLUSIONS: In selected patients with a BA <145 degrees 
      and coaptation depth <=10 mm, CC is related to less MR return or persistence,
      improved EF, and lower New York Heart Association class.

PMID- 24041765
TI  - Early structural valve deterioration of the Trifecta aortic valve biological
      prosthesis: a word of caution.

PMID- 24041766
TI  - Transapical neochord implantation: is tension of artificial chordae tendineae
      dependent on the insertion site?
AB  - OBJECTIVE: Transapical chordae tendineae replacement is a promising new approach
      for mitral leaflet prolapse. However, animal studies have raised concerns that
      the tension of the transapically fixated artificial neochordae might be greater
      than the tension in the neochordae attached to papillary muscle tips, thereby
      reducing repair durability. METHODS: In eight 80-kg pigs, the primary anterior
      leaflet chordae were replaced by a 5-0 polytetrafluoroethylene neochord using a
      miniature in-line force transducer. The neochord was attached first to the
      anterior papillary muscle and, on a second cardiac bypass, transapically to the
      left ventricle apex. Occlusion of the inferior vena cava was performed to examine
      the effect of left ventricle pressure changes on neochord tension to adjust the
      crude data to 95 mm Hg. The maximum slope of the chordal tension curve was
      calculated to compare curve patterns. The data are presented as the mean +/-
      standard deviation. RESULTS: The following tension was measured in the neochordae
      during papillary muscle and transapical fixation, respectively: peak tension
      (crude, 0.39 +/- 0.32 vs 0.50 +/- 0.25 N, P = .17; adjusted, 0.41 +/- 0.30 vs
      0.46 +/- 0.27 N, P = .22), mid-systolic tension (crude, 0.19 +/- 0.12 vs 0.19 +/-
      0.15 N, P = .96; adjusted, 0.28 +/- 0.16 vs 0.19 +/- 0.11 N, P = .12). There was
      a significantly lower maximum slope (dF/dtmax) of the neochord tension curves
      after papillary muscle fixation compared with transapical fixation (7.4 +/- 6.9
      vs 10.3 +/- 7.7 N/s, P = .028). CONCLUSIONS: Overall, the chordal insertion site
      had little influence on the tension in the artificial neochordae compared with
      the interindividual variation. However, abnormal tension fluctuations in the
      transapically fixated neochordae might predispose to leaflet tears and early
      repair failure.

PMID- 24041767
TI  - Acute type I aortic dissection: traditional versus hybrid repair with antegrade
      stent delivery to the descending thoracic aorta.
AB  - OBJECTIVE: We compared the short-term outcomes between patients who had undergone
      classic repair for type I aortic dissection and those who had undergone
      concomitant antegrade stenting in the descending thoracic aorta. METHODS: From
      January 2005 to December 2012, 112 patients were treated for acute type I aortic
      dissection. Eighty-seven patients (group A) underwent traditional operations on
      the ascending and proximal arch (n = 79, 90.8%), total arch (n = 7, 8.1%), or
      ascending aorta (n = 1, 1.2%). Twenty-five patients (group B) underwent ascending
      and proximal arch repair and antegrade stent grafting in the descending thoracic
      aorta. Various concomitant procedures were performed in both groups. The
      circulatory arrest times were similar between the 2 groups. RESULTS: The 30-day
      mortality was 13.8% (n = 12) in group A and 12% (n = 3) in group B. Nine patients
      in group A (10.3%) and 3 in group B (12%) experienced a postoperative stroke. In
      group A, 1 patients (1.5%) developed transient spinal cord ischemia, and in group
      B, 2 patients had transient paraparesis (8.0%). Preoperatively, 24 group A
      patients and 19 group B patients had malperfusion; this condition resolved
      postoperatively in 13 group A patients (54.2%) and 16 group B patients (84.2%; P
      < .037). Eight group A patients (10.8%) and 1 group B patient (4.5%) underwent
      additional postoperative procedures on the thoracoabdominal aorta a median of
      776.5 days (range, 168.5-1102.0) and 54 days postoperatively, respectively.
      CONCLUSIONS: Antegrade endovascular grafting of the descending thoracic aorta
      during repair of acute type I aortic dissection is technically safe, does not
      increase the circulatory arrest time, and could help patients with preoperative
      malperfusion. Long-term follow-up data are needed.

PMID- 24041768
TI  - Antibody response and maternal immunity upon boosting PRRSV-immune sows with
      experimental farm-specific and commercial PRRSV vaccines.
AB  - The porcine reproductive and respiratory syndrome virus (PRRSV) causes
      reproductive failure in sows and respiratory disease in pigs of all ages. Despite
      the frequent use of vaccines to maintain PRRSV immunity in sows, little is known
      on how the currently used vaccines affect the immunity against currently
      circulating and genetically divergent PRRSV variants in PRRSV-immune sows, i.e.
      sows that have a pre-existing PRRSV-specific immunity due to previous infection
      with or vaccination against the virus. Therefore, this study aimed to assess the
      capacity of commercially available attenuated/inactivated PRRSV vaccines and
      autogenous inactivated PRRSV vaccines - prepared according to a previously
      optimized in-house protocol - to boost the antibody immunity against currently
      circulating PRRSV variants in PRRSV-immune sows. PRRSV isolates were obtained
      from 3 different swine herds experiencing PRRSV-related problems, despite regular
      vaccination of gilts and sows against the virus. In a first part of the study,
      the PRRSV-specific antibody response upon booster vaccination with commercial
      PRRSV vaccines and inactivated farm-specific PRRSV vaccines was evaluated in
      PRRSV-immune, non-pregnant replacement sows from the 3 herds. A boost in virus
      neutralizing antibodies against the farm-specific isolate was observed in all sow
      groups vaccinated with the corresponding farm-specific inactivated vaccines. Use
      of the commercial attenuated EU type vaccine boosted neutralizing antibodies
      against the farm-specific isolate in sows derived from 2 farms, while use of the
      commercial attenuated NA type vaccine did not boost farm-specific virus
      neutralizing antibodies in any of the sow groups. Interestingly, the commercial
      inactivated EU type vaccine boosted farm-specific virus-neutralizing antibodies
      in sows from 1 farm. In the second part of the study, a field trial was performed
      at one of the farms to evaluate the booster effect of an inactivated farm
      specific vaccine and a commercial attenuated EU-type vaccine in immune sows at 60
      days of gestation. The impact of this vaccination on maternal immunity and on the
      PRRSV infection pattern in piglets during their first weeks of life was
      evaluated. Upon vaccination with the farm-specific inactivated vaccine, a
      significant increase in farm-specific virus-neutralizing antibodies was detected
      in all sows. Virus-neutralizing antibodies were also transferred to the piglets
      via colostrum and were detectable in the serum of these animals until 5 weeks
      after parturition. In contrast, not all sows vaccinated with the commercial
      attenuated vaccine showed an increase in farm-specific virus-neutralizing
      antibodies and the piglets of this group generally had lower virus-neutralizing
      antibody titers. Interestingly, the number of viremic animals (i.e. animals that
      have infectious virus in their bloodstream) was significantly lower among piglets
      of both vaccinated groups than among piglets of mock-vaccinated sows and this at
      least until 9 weeks after parturition. The results of this study indicate that
      inactivated farm-specific PRRSV vaccines and commercial attenuated vaccines can
      be useful tools to boost PRRSV-specific (humoral) immunity in sows and reduce
      viremia in weaned piglets. 

PMID- 24041769
TI  - Assessing the molecular basis of transferable quinolone resistance in Escherichia
      coli and Salmonella spp. from food-producing animals and food products.
AB  - Enterobacteriaceae resistant to quinolones frequently arise in animals, being
      easily disseminated through the food-chain. The aim of this study was to
      investigate the presence of plasmid-mediated quinolone resistance (PMQR)
      determinants in Salmonella spp. (n=183) and Escherichia coli (n=180) isolates,
      collected from food-producing animals and food products among swine, poultry,
      rabbits and cattle. All isolates were subjected to antimicrobial susceptibility
      testing and molecular screening of PMQR determinants. beta-Lactamase-encoding
      genes, and the quinolone resistance determining region (QRDR) of gyrA, gyrB, parC
      and parE genes were also investigated in PMQR-positive isolates. Plasmid
      characterization was performed by conjugation, followed by replicon-typing.
      Genetic relatedness of PMQR-positive E. coli was examined by Multilocus Sequence
      Typing, while Salmonella was previously serotyped. The association of mobile
      genetic elements and PMQR was investigated through PCR mapping assays. Overall,
      4.1% (15/363) isolates harbored qnrB2 (n=3), qnrB19 (n=3), and qnrS1 (n=9) genes.
      All but one isolate presented one to four mutations in QRDR of gyrA or parC
      genes, which is consistent with the range of MIC values detected (0.19-64 mg/L)
      for ciprofloxacin; 60% (9/15) of qnr-harboring isolates were non-susceptible to
      beta-lactam antibiotics which was justified by the presence of beta-lactamases
      from TEM (TEM-1, n=8; TEM-135, n=1) and SHV (SHV-108, n=1) families. Analysis of
      mobile genetic elements revealed that qnr genes were detected nearby relevant
      genetic elements like intI1, ISEcl2, IS26 and ISCR1 and enclosed in diverse Inc.
      type plasmids. This study illustrated the existence of Qnr-producing E. coli and
      Salmonella from food-producing animals, associated to specific mobile elements
      that might mediate their transference between species and among distinct
      settings.

PMID- 24041770
TI  - Fatal pneumonia caused by Extraintestinal Pathogenic Escherichia coli (ExPEC) in
      a juvenile cat recovered from an animal hoarding incident.
AB  - The current study describes isolation of Extraintestinal Pathogenic Escherichia
      coli (ExPEC) from a juvenile male cat that died after being rescued from an
      animal hoarding incident. Grossly, there was evidence of pneumonia and renal
      abscessation. Histologically, there was diffuse interstitial pneumonia with
      necrosis and necrotizing and suppurative nephritis with colonies of coccobacilli.
      Within the lung, kidney, and mesentery there was necrotizing and suppurative
      vasculitis with thrombosis and coccobacilli. E. coli strain belonging to serotype
      O6:H1 that carried many of the virulence genes associated with ExPEC was isolated
      from the lung and kidney. The cat was part of a community of approximately 60
      cats that lived in a house in a residential neighborhood, in which multiple cats
      had died. The case was of major significance to public health, as first
      responders, animal health professionals, and other community members were likely
      exposed to ExPEC, which is known to have zoonotic potential. It is important that
      pet owners, animal health and public health professionals, and first responders
      be made aware of the potential for zoonotic diseases. 

PMID- 24041771
TI  - Extracellular polymeric substances from copper-tolerance Sinorhizobium meliloti
      immobilize Cu2+.
AB  - The copper tolerance gene of wild-type heavy metal-tolerance Sinorhizobium
      meliloti CCNWSX0020 was mutated by transposon Tn5-a. The mutant was sensitive up
      to 1.4mM Cu(2+). Production, components, surface morphology, and functional
      groups of extracellular polymeric substances (EPS) of the wild-type strains were
      compared with sensitive mutant in immobilization of Cu(2+). EPS produced by S.
      meliloti CCNWSX0020 restricts uptake of Cu(2+). The cell wall EPS were
      categorized based on the compactness and fastness: soluble EPS (S-EPS), loosely
      bound EPS (LB-EPS), and tightly bound EPS (TB-EPS). LB-EPS played a more
      important role than S-EPS and TB-EPS in Cu(2+) immobilization. Scanning electron
      microscopy (SEM) analysis LB-EPS had rough surface and many honeycomb pores,
      making them conducive to copper entry; therefore, they may play a role as a
      microbial protective barrier. Fourier transform-infrared (FT-IR) analysis further
      confirm that proteins and carbohydrates were the main extracellular compounds
      which had functional groups such as carboxyl (COOH), hydroxyl (OH), and amide
      (NH), primarily involved in metal ion binding.

PMID- 24041772
TI  - Conversion of carbon disulfide in air by non-thermal plasma.
AB  - Carbon disulfide (CS2), a typical odorous organic sulfur compound, has adverse
      effects on human health and is a potential threat to the environment. In the
      present study, CS2 conversion in air by non-thermal plasma (NTP) was
      systematically investigated using a link tooth wheel-cylinder plasma reactor
      energized by a DC power supply. The results show that corona discharge is
      effective in removing CS2. The CS2 conversion increases with the increase of
      specific input energy (SIE). Both short-living (e.g. O, OH radicals) and long
      living species contribute to the CS2 conversion, but the short-living species
      play a more important role. Both gaseous and solid products are formed during the
      conversion of CS2. Gaseous products mainly include CO, CO2, OCS, SO2, SO3 and
      H2SO4. The yields of CO and CO2 increase, the yields of OCS and SO2 follow bell
      curves while the sum yield of SO3 and H2SO4 remains constant as SIE increases.
      The solid products, consisting of CO3(2-), SO4(2-) and possible polymeric sulfur,
      deposit on the inner wall and electrodes of the plasma reactor. 

PMID- 24041773
TI  - Timing matters: age-related changes in episodic retrieval control as revealed by
      event-related potentials.
AB  - The retrieval of information from episodic memory involves the engagement of pre
      retrieval control processes that facilitate the recovery of task-relevant
      information. The development of these processes was investigated here by
      comparing neural correlates of retrieval orientation between 13-14-year-old
      adolescents and young adults. In each age group, event-related potentials (ERPs)
      elicited by new test pictures were contrasted across two recognition memory tasks
      (specific vs. general retrieval tasks), which were designed to place greater
      demands on the recovery of perceptual information associated with each picture in
      the specific than in the general task. Memory accuracy was higher in the general
      than in the specific task but did not differ between age groups. In adults, new
      item ERPs at anterior sites were more positive going in the specific than in the
      general task from 400 to 1,200 ms. In adolescents, the onset latency of this
      effect was delayed by 300 ms relative to adults, even though no age differences
      in response speed were obtained in either task. The magnitude of the ERP new item
      effect in adults correlated with response accuracy, consistent with the view that
      pre-retrieval processes facilitate the recovery of task-relevant information. For
      adolescents, this relationship was only obtained for a subset of participants
      with early onsetting ERP effects, supporting the claim that the influence of pre
      retrieval processes depends upon their temporal onset. Together, the findings
      suggest age-related changes in the efficiency of using control processes to
      facilitate successful retrieval while highlighting the role of onset latency in
      mediating these changes.

PMID- 24041774
TI  - Epigenetic modification in neurons of the mollusc Pomacea canaliculata after
      immune challenge.
AB  - In human and rodents, the transcriptional response of neurons to stress is
      related to epigenetic modifications of both DNA and histone proteins. To assess
      the suitability of simple invertebrate models in studying the basic mechanisms of
      stress-related epigenetic modifications, we analyzed epigenetic modifications in
      neurons of the freshwater snail Pomacea canaliculata after the injection of
      Escherichia coli-derived lipopolysaccharide (LPS). The phospho-acetylation of
      histone H3, together with the induction of stress-related factors, c-Fos and
      HSP70, were evaluated in large and small neurons of the pedal ganglia of sham-
      and LPS-injected snails. Immunocytochemical investigations showed that after LPS
      injection, the immunopositivity towards phospho (Ser10)-acetyl (Lys14)-histone H3
      and c-Fos increases in the nuclei of small gangliar neurons. Western blot
      analysis confirmed a significant increase of phospho (Ser10)-acetyl (Lys14)
      histone H3 in nuclear extracts from 2h LPS-injected animals. c-Fos protein levels
      were significantly augmented 6h after LPS injection. Immunocytochemistry and
      western blot indicated that no changes occurred in HSP70 distribution and protein
      levels. To our knowledge this is the first demonstration of epigenetic changes in
      molluscan neurons after an immune challenge and indicate the gastropod P.
      canaliculata as a suitable model for evolutionary and translational studies on
      stress-related epigenetic modifications.

PMID- 24041775
TI  - Sexual activity counteracts the suppressive effects of chronic stress on adult
      hippocampal neurogenesis and recognition memory.
AB  - Adult neurogenesis can be influenced by a variety of factors. Stress is one of
      the most potent inhibitors of hippocampal neurogenesis. Stress effects on adult
      hippocampal neurogenesis are affected differently by environmental factors,
      including social interaction. Sexual behavior between males and females in a
      social context has been suggested to influence neurogenesis and enhance
      hippocampal cell proliferation. However, the mechanisms of action of sexual
      interaction, the possible changes relative to stress state, and its effects on
      learning and memory remain uncertain. The current study examined the influence of
      sexual interaction on neurological responses in adult male mice and the function
      of sexual interaction relative to recognition memory in stress states. Changes in
      the expression of neurotrophic and transcription factors were assessed in
      reference to stress and/or sexual behaviors. The survival of newly generated
      cells and their rate of differentiation into neurons were determined in the
      hippocampus of chronically stressed and/or sexually experienced mice. Finally, to
      evaluate whether sexual experience alters adult hippocampal function, we tested
      learning and memory in a recognition memory task. The results demonstrated that
      sexual activity increased the expression of brain-derived neurotrophic factor,
      tyrosine kinase B, and cAMP response element-binding factor. Furthermore, the
      results supported the view that sexual interaction could be helpful for buffering
      adult hippocampal neurogenesis and recognition memory function against the
      suppressive actions of chronic stress. 

PMID- 24041776
TI  - Concurrent emotional pictures modulate temporal order judgments of spatially
      separated audio-tactile stimuli.
AB  - Although attention can be captured toward high-arousal stimuli, little is known
      about how perceiving emotion in one modality influences the temporal processing
      of non-emotional stimuli in other modalities. We addressed this issue by
      presenting observers spatially uninformative emotional pictures while they
      performed an audio-tactile temporal-order judgment (TOJ) task. In Experiment 1,
      audio-tactile stimuli were presented at the same location straight ahead of the
      participants, who had to judge "which modality came first?". In Experiments 2 and
      3, the audio-tactile stimuli were delivered one to the left and the other to the
      right side, and participants had to judge "which side came first?". We found both
      negative and positive high-arousal pictures to significantly bias TOJs towards
      the tactile and away from the auditory event when the audio-tactile stimuli were
      spatially separated; by contrast, there was no such bias when the audio-tactile
      stimuli originated from the same location. To further examine whether this bias
      is attributable to the emotional meanings conveyed by the pictures or to their
      high arousal effect, we compared and contrasted the influences of near-body
      threat vs. remote threat (emotional) pictures on audio-tactile TOJs in Experiment
      3. The bias manifested only in the near-body threat condition. Taken together,
      the findings indicate that visual stimuli conveying meanings of near-body
      interaction activate a sensorimotor functional link prioritizing the processing
      of tactile over auditory signals when these signals are spatially separated. In
      contrast, audio-tactile signals from the same location engender strong crossmodal
      integration, thus counteracting modality-based attentional shifts induced by the
      emotional pictures. 

PMID- 24041778
TI  - Does tonality boost short-term memory in congenital amusia?
AB  - Congenital amusia is a neuro-developmental disorder of music perception and
      production. Recent findings have demonstrated that this deficit is linked to an
      impaired short-term memory for tone sequences. As it has been shown before that
      non-musicians' implicit knowledge of musical regularities can improve short-term
      memory for tone information, the present study investigated if this type of
      implicit knowledge could also influence amusics' short-term memory performance.
      Congenital amusics and their matched controls, who were non-musicians, had to
      indicate whether sequences of five tones, presented in pairs, were the same or
      different; half of the pairs respected musical regularities (tonal sequences) and
      the other half did not (atonal sequences). As previously reported for non
      musician participants, the control participants showed better performance (as
      measured with d') for tonal sequences than for atonal ones. While this
      improvement was not observed in amusics, both control and amusic participants
      showed faster response times for tonal sequences than for atonal sequences. These
      findings suggest that some implicit processing of tonal structures is potentially
      preserved in congenital amusia. This observation is encouraging as it strengthens
      the perspective to exploit implicit knowledge to help reducing pitch perception
      and memory deficits in amusia. 

PMID- 24041777
TI  - Endocannabinoids blunt the augmentation of synaptic transmission by serotonin 2A
      receptors in the nucleus tractus solitarii (nTS).
AB  - Serotonin (5-Hydroxytryptamine, 5-HT) and the 5-HT2 receptor modulate
      cardiovascular and autonomic function in part through actions in the nTS, the
      primary termination and integration point for cardiorespiratory afferents in the
      brainstem. In other brain regions, 5-HT2 receptors (5-HT2R) modify synaptic
      transmission directly, as well as through 5-HT2AR-induced endocannabinoid
      release. This study examined the role of 5-HT2AR as well as their interaction
      with endocannabinoids on neurotransmission in the nucleus tractus solitarii
      (nTS). Excitatory postsynaptic currents (EPSCs) in monosynaptic nTS neurons were
      recorded in the horizontal brainstem slice during activation and blockade of 5
      HT2ARs. 5-HT2AR activation augmented solitary tract (TS) evoked EPSC amplitude
      whereas 5-HT2AR blockade depressed TS-EPSC amplitude at low and high TS
      stimulation rates. The 5-HT2AR-induced increase in neurotransmission was reduced
      by endocannabinoid receptor block and increased endogenous endocannabinoids in
      the synaptic cleft during high frequency, but not low, TS stimulation.
      Endocannabinoids did not tonically modify EPSCs. These data suggest 5-HT acting
      through the 5-HT2AR is an excitatory neuromodulator in the nTS and its effects
      are modulated by the endocannabinoid system. 

PMID- 24041779
TI  - Epidemiology of imported malaria give support to the hypothesis of 'long-term'
      semi-immunity to malaria in sub-Saharan African migrants living in France.
AB  - BACKGROUND: Short-term semi-immunity to malaria in sub-Saharan African migrants
      who have recently arrived in non-endemic countries results in less severe
      imported malaria. Our aim was to investigate the factors associated with imported
      malaria that would favour the hypothesis of a 'long-term' semi-immunity to
      malaria in adult travellers of sub-Saharan origin living in France and visiting
      family or relatives in their country of origin (VFR group). METHOD: The
      epidemiological, clinical and biological characteristics of imported Plasmodium
      falciparum malaria in VFR were compared with those of travellers of European
      origin (TEO). Newly arrived African migrants and European expatriates were
      excluded. RESULTS: This retrospective study included 106 adult VFR (30%) and 240
      adult TEO (70%) with imported P. falciparum malaria treated at the University
      Hospital Center of Bordeaux between 2000 and 2007. The main regions visited were
      West Africa (58%) and Central Africa (34%). P. falciparum was associated with
      severe malaria in 8% of patients (VFR 3% vs. TEO 11%), of which two TEO died. In
      univariate analysis, the factors associated with P. falciparum malaria in VFR vs.
      TEO were: female sex, younger age, less frequent use of mosquito nets, poor
      compliance with chemoprophylaxis, less severe malaria without death, less severe
      thrombocytopenia and a tendency towards a lower level of parasitaemia and higher
      haemoglobinaemia. In multivariate analysis, the only factor to be independently
      associated with P. falciparum malaria in VFR compared to TEO was less frequent
      severe malaria. CONCLUSIONS: Our results give support to the hypothesis of 'long
      term' semi-immunity to malaria in VFR living in France.

PMID- 24041780
TI  - Phthalates and the diets of U.S. children and adolescents.
AB  - BACKGROUND: Di-2-ethylhexylphthalate (DEHP) is an ester of phthalic acid commonly
      found in processed foods. DEHP may contribute to obesity and insulin resistance
      in children and adolescents, yet dietary exposures have been not been studied in
      this vulnerable subpopulation. OBJECTIVE: To assess diet and its relation to
      urinary phthalates in a nationally representative sample of US children and
      adolescents. DESIGN: Cross-sectional analysis of 24-h dietary recall and urinary
      phthalate metabolites from 2743 6-19 year olds participating in the 2003-8
      National Health and Nutrition Examination Surveys. Regression analyses examined
      relationships of food consumption with log-transformed metabolite concentrations,
      examined as low-molecular weight, high molecular weight and di-2
      ethylhexylphthalate categories, controlling for urinary creatinine, age group,
      body mass index category, race/ethnicity, caloric intake and gender. RESULTS: We
      identified a -0.04% (95% CI: -0.08, -0.01) increment in di-2-ethylhexylphthalate
      metabolite concentration/additional gram fruit consumption, a +0.01%
      increment/additional calorie dietary intake (95% CI: +0.003, +0.02), and a +0.09%
      (95% CI: +0.02, +0.17) increment/additional gram meat/poultry/fish consumption.
      Soy consumption (-0.40% increment/additional gram consumed, 95% CI: -0.66, -0.14)
      was inversely associated with di-2-ethylhexylphthalate, while poultry (+0.23%
      increment/additional gram consumed, 95% CI: +0.12, +0.35) was positively
      associated. Findings were robust to examination of metabolite concentrations per
      unit body mass index and weight, and inclusion of fasting time. CONCLUSIONS: Diet
      contributes to urinary phthalate concentrations in children and adolescents.
      Further study is needed to examine the implications of di-2-ethylhexylphthalate
      exposure, especially earlier in life, when more permanent metabolic changes may
      occur.

PMID- 24041781
TI  - Do corticosteroids prevent postherpetic neuralgia?

PMID- 24041782
TI  - Does immediate total-body computed tomography reduce mortality and time in the
      emergency department for trauma patients?

PMID- 24041783
TI  - Transient and sustained changes in operational performance, patient evaluation,
      and medication administration during electronic health record implementation in
      the emergency department.
AB  - STUDY OBJECTIVE: Little is known about the transient and sustained operational
      effects of electronic health records on emergency department (ED) performance. We
      quantify how the implementation of a comprehensive electronic health record was
      associated with metrics of operational performance, test ordering, and medication
      administration at a single-center ED. METHODS: We performed a longitudinal
      analysis of electronic data from a single, suburban, academic ED during 28 weeks
      between May 2011 and November 2011. We assessed length of stay, use of diagnostic
      testing, medication administration, radiologic imaging, and patient satisfaction
      during a 4-week baseline measurement period and then tracked changes in these
      variables during the 24 weeks after implementation of the electronic health
      record. RESULTS: Median length of stay increased and patient satisfaction was
      reduced transiently, returning to baseline after 4 to 8 weeks. Rates of
      laboratory testing, medication administration, overall radiologic imaging,
      radiographs, computed tomography scans, and ECG ordering all showed sustained
      increases throughout the 24 weeks after electronic health record implementation.
      CONCLUSION: Electronic health record implementation in this single-center study
      was associated with both transient and sustained changes in metrics of ED
      performance, as well as laboratory and medication ordering. Understanding ways in
      which an ED can be affected by electronic health record implementation is
      critical to providing insight about ways to mitigate transient disruption and to
      maximize potential benefits of the technology.

PMID- 24041784
TI  - Elucidation of the role of LMO2 in human erythroid cells.
AB  - LIM-only protein 2 (LMO2) is a non-DNA-binding component of a protein complex
      containing master regulators of hematopoiesis, including GATA-1, SCL/TAL1, and
      LDB1. However, the role of LMO2 in human erythroid differentiation is unclear.
      LMO2 knockdown in hemin-treated K562 cells reduced the benzidine-positive cell
      ratio, suggesting that LMO2 retards hemin-mediated K562 cell differentiation.
      Microarray analysis using K562 cells after siRNA-mediated LMO2 knockdown
      indicated that 177 and 78 genes were upregulated and downregulated (>1.5-fold),
      respectively. The downregulated gene ensemble contained prototypical erythroid
      genes (HBB, SLC4A1). Whereas LMO2 knockdown did not affect GATA-1 or SCL/TAL1
      expression, it resulted in significantly reduced chromatin occupancy of GATA-1,
      SCL/TAL1, and LDB1 at the beta-globin locus control region and SLC4A1 locus in
      both K562 cells and human induced pluripotent stem cell-derived erythroid cells.
      Introduction of GATA-1 mutations, shown to impair direct interaction with LMO2,
      significantly diminished chromatin occupancy. On the other hand, knockdown of
      either SCL/TAL1 or LDB1 also resulted in significantly reduced chromatin
      occupancy of GATA-1 at endogenous loci, suggesting that impaired assembly of
      these components also affects GATA-1 chromatin occupancy. In an ex vivo model of
      erythroid differentiation from CD34(+) cells, LMO2 protein level peaked on day 5
      and decreased at later stages of differentiation. The LMO2 expression pattern was
      similar to those of GATA-1 and SCL/TAL1. Furthermore, shRNA-mediated LMO2
      knockdown in primary erythroblasts suggested that LMO2 regulates HBB, HBA, and
      SLC4A1 expression. LMO2 contributes to GATA-1 target gene expression by affecting
      assembly of the GATA-SCL/TAL1 complex components at endogenous loci.

PMID- 24041785
TI  - Interleukin 22 inhibits intracellular growth of Mycobacterium tuberculosis by
      enhancing calgranulin A expression.
AB  - Previously, we found that interleukin 22 (IL-22) inhibits intracellular growth of
      Mycobacterium tuberculosis in human monocyte-derived macrophages (MDMs). In the
      current study, we determined the mechanisms underlying these effects. We found
      that W7, a phagolysosomal fusion inhibitor, abrogates IL-22-dependent M.
      tuberculosis growth inhibition in MDMs, suggesting that IL-22 acts through
      enhanced phagolysosomal fusion. Our microarray analysis indicated that
      recombinant IL-22 (rIL-22) enhances the expression of an intracellular signaling
      molecule, calgranulin A. This was confirmed by real-time polymerase chain
      reaction, Western blot, and confocal microscopy. Calgranulin A small interfering
      RNA (siRNA) abrogated rIL-22-dependent growth inhibition of M. tuberculosis in
      MDMs. IL-22 enhanced Rab7 expression and downregulated Rab14 expression of M.
      tuberculosis-infected MDMs, and these effects were reversed by calgranulin A
      siRNA. These results suggest that M. tuberculosis growth inhibition by IL-22
      depends on calgranulin A and enhanced phagolysosomal fusion, which is associated
      with increased Rab7 and reduced Rab14 expression. 

PMID- 24041786
TI  - Angiotensin II receptor type 1--a novel target for preventing neonatal meningitis
      in mice by Escherichia coli K1.
AB  - The increasing incidence of Escherichia coli K1 meningitis due to escalating
      antibiotic resistance warrants alternate treatment options to prevent this deadly
      disease. We screened a library of small molecules from the National Institutes of
      Health clinical collection and identified telmisartan, an angiotensin II receptor
      type 1 (AT1R) blocker, as a potent inhibitor of E. coli invasion into human brain
      microvascular endothelial cells (HBMECs). Immunoprecipitation studies revealed
      that AT1R associates with endothelial cell gp96, the receptor in HBMECs for E.
      coli outer membrane protein A. HBMECs pretreated with telmisartan or transfected
      with AT1R small interfering RNA were resistant to E. coli invasion because of
      downregulation of protein kinase C-alpha phosphorylation. Administration of a
      soluble derivative of telmisartan to newborn mice before infection with E. coli
      prevented the onset of meningitis and suppressed neutrophil infiltration and
      glial cell migration in the brain. Therefore, telmisartan has potential as an
      alternate treatment option for preventing E. coli meningitis. 

PMID- 24041787
TI  - Reply to Plotz et al.

PMID- 24041788
TI  - Temporal trends in syphilis and gonorrhea incidences in guangdong province,
      china.
AB  - The high burden of syphilis in China presents a unique opportunity to examine
      temporal trends. This study used wavelet transformation and Fourier analysis to
      assess the presence of temporal oscillations in the incidence of syphilis among
      adults, gonorrhea, and congenital syphilis over 11 years in China's largest
      province. This study found a significant annual oscillation trend in the
      incidence of adult syphilis, consistent with a peak during July-September, which
      was 4-fold higher than the trough, which occurred during January-March. A similar
      but dampened trend was observed in the incidence of gonorrhea, and no trend was
      observed for the incidence of congenital syphilis. Further research on the
      temporal oscillation of the incidence of syphilis is needed. 

PMID- 24041789
TI  - Safety and immunogenicity of a vero cell culture-derived whole-virus influenza
      A(H5N1) vaccine in a pediatric population.
AB  - BACKGROUND: Children are highly vulnerable to infection with novel influenza
      viruses. It is essential to develop candidate pandemic influenza vaccines that
      are safe and effective in the pediatric population. METHODS: Infants and children
      aged 6-35 months and 3-8 years, respectively, were randomized to receive 2
      immunizations with a 7.5-ug or 3.75-ug hemagglutinin (HA) dose of a nonadjuvanted
      whole-virus A/Vietnam(H5N1) vaccine; adolescents aged 9-17 years received a 7.5
      ug dose only. A subset of participants received a booster immunization with an
      A/Indonesia(H5N1) vaccine approximately 1 year later. HA and neuraminidase
      antibody responses were assessed. RESULTS: Vaccination was safe and well
      tolerated; adverse reactions were transient and predominantly mild. Two
      immunizations with the 7.5-ug dose of A/Vietnam vaccine induced virus
      microneutralization (MN) titers of >=1:20 against the A/Vietnam strain in 68.8%
      85.4% of participants in the different age groups. After the booster, 93.1%-100%
      of participants achieved MN titers of >=1:20 against the A/Vietnam and
      A/Indonesia strains. Neuraminidase-inhibiting antibodies were induced in >=90% of
      participants after 2 immunizations with the 7.5 ug A/Vietnam vaccine and in 100%
      of participants after the booster. CONCLUSIONS: A whole-virus influenza A(H5N1)
      vaccine is suitable for prepandemic or pandemic immunization in a pediatric
      population. CLINICAL TRIALS REGISTRATION: NCT01052402.

PMID- 24041790
TI  - Noncalcified coronary atherosclerotic plaque and immune activation in HIV
      infected women.
AB  - BACKGROUND: Little is known about coronary plaque in human immunodeficiency virus
      (HIV)-infected women. METHODS: Sixty HIV-infected and 30 non-HIV-infected women
      without symptoms or history of cardiovascular disease were recruited to assess
      coronary plaque with coronary computed tomographic angiography and immune
      activation. Data from 102 HIV-infected men and 41 non-HIV-infected male controls
      were compared. RESULTS: HIV-infected women demonstrated significantly higher
      percentages of segments with noncalcified plaque (mean +/- SD, 74% +/- 28% vs 23%
      +/- 39% compared to female control subjects; median [interquartile range], 75%
      [63%-100%] vs 0% [0%-56%]; P = .007) and more segments with noncalcified plaque
      (mean +/- SD, 0.92 +/- 1.48 vs 0.40 +/- 1.44; median [interquartile range], 0 [0
      2] vs 0 [0-0]; P = .04). Immune activation parameters, including soluble CD163
      (sCD163; P = .006), CXCL10 (P = .002), and percentages of CD14(+)CD16(+)
      monocytes (P = .008), were higher in HIV-infected women than in female control
      subjects, but no differences were seen in general inflammatory markers. Among HIV
      infected women with noncalcified coronary plaque, sCD163 levels were
      significantly higher than in HIV-infected women without noncalcified plaque (P =
      .04). In multivariate modeling for sCD163 levels among male and female subjects,
      significant effects of HIV (P < .0001), age (P = .002), and sex (P = .0002) were
      seen. CONCLUSIONS: Young, asymptomatic, HIV-infected women, demonstrate increased
      noncalcified coronary plaque and increased immune activation, particularly
      monocyte activation. Independent effects of sex, HIV status, and aging on immune
      activation may contribute to cardiovascular disease in this population. CLINICAL
      TRIALS REGISTRATION: NCT00455793.

PMID- 24041791
TI  - Broadly protective protein-based pneumococcal vaccine composed of pneumolysin
      toxoid-CbpA peptide recombinant fusion protein.
AB  - BACKGROUND:  Pneumococcus, meningococcus, and Haemophilus influenzae cause a
      similar spectrum of infections in the ear, lung, blood, and brain. They share
      cross-reactive antigens that bind to the laminin receptor of the blood-brain
      barrier as a molecular basis for neurotropism, and this step in pathogenesis was
      addressed in vaccine design. METHODS:  Biologically active peptides derived from
      choline-binding protein A (CbpA) of pneumococcus were identified and then
      genetically fused to L460D pneumolysoid. The fusion construct was tested for
      vaccine efficacy in mouse models of nasopharyngeal carriage, otitis media,
      pneumonia, sepsis, and meningitis. RESULTS:  The CbpA peptide-L460D pneumolysoid
      fusion protein was more broadly immunogenic than pneumolysoid alone, and
      antibodies were active in vitro against Streptococcus pneumoniae, Neisseria
      meningitidis, and H. influenzae. Passive and active immunization protected mice
      from pneumococcal carriage, otitis media, pneumonia, bacteremia, meningitis, and
      meningococcal sepsis. CONCLUSIONS:  The CbpA peptide-L460D pneumolysoid fusion
      protein was broadly protective against pneumococcal infection, with the potential
      for additional protection against other meningeal pathogens.

PMID- 24041792
TI  - Safety and antiviral activity of the HCV entry inhibitor ITX5061 in treatment
      naive HCV-infected adults: a randomized, double-blind, phase 1b study.
AB  - BACKGROUND: Hepatitis C virus (HCV) entry involves scavenger receptor B1 (SRB1).
      In vitro, SRB1 inhibition by ITX5061 impedes HCV replication. METHODS:
      Multicenter study to assess safety/activity of ITX5061 in previously untreated,
      noncirrhotic, HCV genotype 1 infected adults. Design included sequential cohorts
      of 10 subjects with ITX5061 (n = 8) or placebo (n = 2) to escalate duration (3 to
      14 to 28 days) or deescalate dose (150 to 75 to 25 mg) based on predefined
      criteria for safety and activity (>= 4 of 8 subjects with HCV RNA decline >= 1
      log10 IU/mL). RESULTS: Thirty subjects enrolled in 3 cohorts: ITX5061 150 mg/day
      by mouth for 3 (A150), 14 (B150), and 28 (C150) days. Six subjects had grade >= 3
      adverse events (one in placebo); none were treatment related. One of the 7 C150
      subjects (14.3%, 95% confidence interval [CI], .7%-55.4%) had >= 1 log10 IU/mL
      decline in HCV RNA (1.49 log10 IU/mL), whereas none of the 6 placebo, 8 A150 or 8
      B150 subjects showed such decline. CONCLUSIONS: Oral ITX5061 150 mg/day for up to
      28 days was safe and well tolerated. In the 28-day cohort, 1 of 7 subjects showed
      antiviral activity; however, predefined criteria for antiviral activity were not
      met at the doses and durations studied.

PMID- 24041794
TI  - The intestinal pathobiome: its reality and consequences among infants and young
      children in resource-limited settings.

PMID- 24041793
TI  - Staphylococcal enterotoxin P predicts bacteremia in hospitalized patients
      colonized with methicillin-resistant Staphylococcus aureus.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization
      predicts later infection, with both host and pathogen determinants of invasive
      disease. METHODS: This nested case-control study evaluates predictors of MRSA
      bacteremia in an 8-intensive care unit (ICU) prospective adult cohort from 1
      September 2003 through 30 April 2005 with active MRSA surveillance and collection
      of ICU, post-ICU, and readmission MRSA isolates. We selected MRSA carriers who
      did (cases) and those who did not (controls) develop MRSA bacteremia. Generating
      assembled genome sequences, we evaluated 30 MRSA genes potentially associated
      with virulence and invasion. Using multivariable Cox proportional hazards
      regression, we assessed the association of these genes with MRSA bacteremia,
      controlling for host risk factors. RESULTS: We collected 1578 MRSA isolates from
      520 patients. We analyzed host and pathogen factors for 33 cases and 121
      controls. Predictors of MRSA bacteremia included a diagnosis of cancer, presence
      of a central venous catheter, hyperglycemia (glucose level, >200 mg/dL), and
      infection with a MRSA strain carrying the gene for staphylococcal enterotoxin P
      (sep). Receipt of an anti-MRSA medication had a significant protective effect.
      CONCLUSIONS: In an analysis controlling for host factors, colonization with MRSA
      carrying sep increased the risk of MRSA bacteremia. Identification of risk
      adjusted genetic determinants of virulence may help to improve prediction of
      invasive disease and suggest new targets for therapeutic intervention.

PMID- 24041795
TI  - Value of Plasmodium falciparum histidine-rich protein 2 level and malaria
      retinopathy in distinguishing cerebral malaria from other acute encephalopathies
      in Kenyan children.
AB  - BACKGROUND: The diagnosis of cerebral malaria is problematic in malaria-endemic
      areas because encephalopathy in patients with parasitemia may have another cause.
      Abnormal retinal findings are thought to increase the specificity of the
      diagnosis, and the level of histidine-rich protein 2 (HRP2) may reflect the
      parasite biomass. METHODS: We examined the retina and measured plasma HRP2 levels
      in children with acute nontraumatic encephalopathy in Kenya. Logistic regression,
      with HRP2 level as an independent variable and World Health Organization-defined
      cerebral malaria and/or retinopathy as the outcome, was used to calculate malaria
      attributable fractions (MAFs) and retinopathy-attributable fractions (RAFs).
      RESULTS: Of 270 children, 140 (52%) had peripheral parasitemia, 80 (30%) had
      malaria retinopathy, and 164 (61%) had an HRP2 level of >0 U/mL. During 2006
      2011, the incidence of HRP2 positivity among admitted children declined by 49
      cases per 100 000 per year (a 78% reduction). An HRP2 level of >0 U/mL had a MAF
      of 93% for cerebral malaria, with a MAF of 97% observed for HRP2 levels of >= 10
      U/mL (the level of the best combined sensitivity and specificity). HRP2 levels of
      >0 U/mL had a RAF of 77% for features of retinopathy combined, with the highest
      RAFs for macular whitening (99%), peripheral whitening (98%), and hemorrhages
      (90%). CONCLUSION: HRP2 has a high attributable fraction for features of malarial
      retinopathy, supporting its use in the diagnosis of cerebral malaria. HRP2
      thresholds improve the specificity of the definition.

PMID- 24041796
TI  - Ratio of monocytes to lymphocytes in peripheral blood identifies adults at risk
      of incident tuberculosis among HIV-infected adults initiating antiretroviral
      therapy.
AB  - BACKGROUND: Eight decades ago, the ratio of monocytes to lymphocytes (hereafter,
      the "ML ratio") was noted to affect outcomes of mycobacterial infection in
      rabbits. Recent transcriptomic studies support a role for relative proportions of
      myeloid and lymphoid transcripts in tuberculosis outcomes. The ML ratio in
      peripheral blood is known to be governed by hematopoietic stem cells with
      distinct biases. METHODS: The predictive value of the baseline ML ratio was
      modeled in 2 prospective cohorts of HIV-infected adults starting cART in South
      Africa (primary cohort, 1862 participants; replication cohort, 345 participants).
      Incident tuberculosis was diagnosed with clinical, radiographic, and
      microbiologic methods per contemporary guidelines. Kaplan-Meier survival analyses
      and Cox proportional hazards modeling were conducted. RESULTS: The incidence rate
      of tuberculosis differed significantly by baseline ML ratio: 32.61 (95%
      confidence interval [CI], 15.38-61.54), 16.36 (95% CI, 12.39-21.23), and 51.80
      (95% CI, 23.10-101.71) per 1000 patient-years for ML ratios of less than the 5th
      percentile, between the 5th and 95th percentiles, and greater than the 95th
      percentile, respectively (P = .007). Neither monocyte counts nor lymphocyte
      counts alone were associated with tuberculosis. After adjustment for sex, World
      Health Organization human immunodeficiency virus disease stage, CD4(+) T-cell
      counts, and previous history of tuberculosis, hazards of disease were
      significantly higher for patients with ML ratios of less than the 5th percentile
      or greater than the 95th percentile (adjusted hazard ratio, 2.47; 95% CI, 1.39
      4.40; P = .002). CONCLUSIONS: The ML ratio may be a useful, readily available
      tool to stratify the risk of tuberculosis and suggests involvement of
      hematopoietic stem cell bias in tuberculosis pathogenesis.

PMID- 24041798
TI  - Immune activation and coronary atherosclerosis in HIV-infected women: where are
      we now, and where will we go next?

PMID- 24041797
TI  - Etiology of diarrhea in Bangladeshi infants in the first year of life analyzed
      using molecular methods.
AB  - BACKGROUND: Diarrhea causes enormous morbidity and mortality in developing
      countries, yet the relative importance of multiple potential enteropathogens has
      been difficult to ascertain. METHODS: We performed a longitudinal cohort study
      from birth to 1 year of age in 147 infants in Dhaka, Bangladesh. Using multiplex
      polymerase chain reaction, we analyzed 420 episodes of diarrhea and 1385 monthly
      surveillance stool specimens for 32 enteropathogen gene targets. For each infant
      we examined enteropathogen quantities over time to ascribe each positive target
      as a probable or less-likely contributor to diarrhea. RESULTS: Multiple
      enteropathogens were detected by the first month of life. Diarrhea was associated
      with a state of overall pathogen excess (mean number of enteropathogen gene
      targets (+/- SE), 5.6 +/- 0.1 vs 4.3 +/- 0.1 in surveillance stool specimens; P <
      .05). After a longitudinal, quantitative approach was applied to filter out less
      likely contributors, each diarrheal episode still had an average of 3.3 probable
      or dominant targets. Enteroaggregative Escherichia coli, Campylobacter,
      enteropathogenic E. coli, rotavirus, and Entamoeba histolytica were the most
      frequent probable contributors to diarrhea. Rotavirus was enriched in moderate to
      severe diarrheal episodes. CONCLUSIONS: In this community-based study diarrhea
      seemed to be a multipathogen event and a state of enteropathogen excess above a
      high carriage baseline.

PMID- 24041799
TI  - Innate immune dysfunction in RSV: what is the role of ventilation?

PMID- 24041800
TI  - Gender sameness and difference in recovery from heroin dependence: a qualitative
      exploration.
AB  - BACKGROUND: In recent years, 'recovery' has become a central, yet controversial,
      concept within the international drug and alcohol field. This paper explores
      gender sameness and difference in recovery from heroin dependence with reference
      to gender theory, the existing literature on women and drugs, and the concept of
      recovery capital. METHODS: Data were generated from 77 qualitative interviews
      conducted with 40 current or ex-heroin users (21 men and 19 women). Coded data
      were analysed using framework and key themes were mapped onto the four components
      of recovery capital: social capital, physical capital, human capital, and
      cultural capital. Differences between the views and experiences of male and
      female participants were then explored. RESULTS: Participants had limited social,
      physical and human capital but greater cultural resources. Although women
      reported more physical and sexual abuse than the men, they had better family and
      social relationships and more access to informal support, including material
      assistance and housing. Women also seemed to be better at managing money and more
      concerned with their physical appearance. Despite the salience of gender,
      individuals had diverse recovery resources that reflected a complex mix of
      intrapersonal, interpersonal and structural factors. CONCLUSIONS: Findings are
      consistent with increasing feminist interest in intersectionality and contribute
      to a more gender-sensitive understanding of recovery. Gender was an important
      structure in shaping our participants' experiences, but there was no evidence of
      an 'essential' female recovery experience and women did not necessarily have less
      recovery resources than men. Whilst useful, the concept of recovery capital has a
      number of definitional and conceptual limitations that indicate a need for more
      empirical research to improve its utility in policy and practice.

PMID- 24041801
TI  - Flow cytometric analysis for detection of tumor-initiating cells in feline
      mammary carcinoma cell lines.
AB  - A small population of cells known as tumor-initiating cells (TICs), which have
      the capacity to self-renew, differentiate, and form tumors at high frequency, has
      a potential role in tumor initiation, aggression, and recurrence. In human breast
      cancers, TICs are identified by surface markers, such as CD44 and CD24, and an
      aldefluor assay based on aldehyde dehydrogenase activity (ALDH(+)) using flow
      cytometry. However, the usefulness of surface markers CD44 and CD24 and ALDH
      activity in feline mammary carcinomas remains largely elusive. We attempted to
      identify CD44(+)CD24(-) and ALDH(+) cells using 8 feline mammary carcinoma cell
      lines, including FKNp, which was obtained from a primary lesion, and the capacity
      to generate tumor nodules was analyzed in immunodeficient mice injected with
      ALDH(+) FKNp-derived cells. The CD44(+)CD24(-) and ALDH(+) cells were detected in
      all cell lines derived from feline mammary carcinomas. Xenograft transplantation
      into immunodeficient mice demonstrated that as few as 1 * 10(2) ALDH(+) cells
      could initiate tumor growth in 1 out of 4 mice, while 1 * 10(3) ALDH(+) cells
      initiated tumor growth in 5 out of 6 mice. However, 1 * 10(3) ALDH(-) cells
      failed to initiate tumors in all the tested mice. ALDH(+)-derived tumors
      contained both ALDH(+) and ALDH(-) cells, indicating that ALDH(+) FKNp-derived
      cells had higher tumorigenicity than ALDH(-) cells. These results suggest that
      TICs may exist in feline mammary carcinomas, and further characterization of
      CD44(+)CD24(-) and ALDH(+) cells is needed to define novel therapies targeted
      against TICs. This study provides the foundation for elucidating the contribution
      of TICs in tumorigenesis.

PMID- 24041802
TI  - Patient-based outcomes and quality of life after salvageable wartime extremity
      vascular injury.
AB  - OBJECTIVE: To date, contemporary studies on wartime vascular trauma have focused
      on acute management strategies and early results, with no characterization of
      enduring functional limb salvage or its relation to quality of life. The
      objective of this study was to describe long-term, patient-based quality of life
      and function after extremity vascular injury (EVI). METHODS: The Joint Theater
      Trauma Registry was queried for U.S. troops with EVI. Injury and management data
      was obtained and the Medical Outcomes Study Short Form 36 (SF-36) Health Survey
      administered after patient contact and consent. Demographic, injury, and
      management variables were analyzed and examined for correlation with the primary
      end points of favorable or unfavorable outcome defined by SF-36 Mental (MCS) or
      Physical Component Summary (PCS) scores of >42 or <42 (effect size >= 0.8).
      RESULTS: Surveys were completed by 214 patients, who were a median age of 25
      years (range, 19-52 years). The Injury Severity Score was 15.3 +/- 8.6 and the
      Mangled Extremity Severity Score was 5.65 +/- 1.4. Amputation-free survival was
      84% at mean follow-up of 61 +/- 24 months. Overall SF-36 PCS and MCS scores were
      43.0 +/- 9.2 and 46.6 +/- 12.4, respectively, with 92 respondents (43%) reporting
      favorable outcomes on both MCS and PCS. On multivariate analysis, older age,
      severe extremity injury (Mangled Extremity Severity Scores >= 7), and chronic
      pain were predictive of unfavorable physical outcomes (P < .05). Presence of
      pain, nerve injury, and junior rank (<E7) were predictive of unfavorable MCS
      scores (P < .05). Higher educational background (baccalaureate or above) was
      associated with favorable outcome (P < .05). CONCLUSIONS: This study reports the
      first long-term patient-centered outcomes data after wartime EVI. At 5 years
      after injury, quality-of-life measures are reduced compared with national norms.
      Understanding high-risk characteristics, both demographic- and injury-specific,
      that are associated with unfavorable outcomes will help guide future acute
      management and long-term recovery strategies.

PMID- 24041803
TI  - Graner's procedure in Kienbock disease: a series of four cases with 25years of
      follow-up.
AB  - Advanced stages of Kienbock's disease are treated by several techniques, one of
      which is Graner's procedure, nearly abandoned nowadays. The results of long-term
      follow-up of a series of four cases Graner's procedure are presented. Four
      patients were reviewed with a follow-up of 25years. There were two women and two
      men mean aged 37years at the time of surgery. Two of them were manual workers.
      Graner's procedure was the first surgery in three cases and secondary to failure
      of radius shortening in one case of Stage IIIa. Three patients underwent bone
      healing and the fourth benefited secondarily from radiocarpal arthrodesis. At
      maximal follow-up, the mean DASH score was 36.6 and pain assessed by visual
      analogic scale was 3.25 out of 10; the range of movement was half of the opposite
      side; the wrist strength was 80.9% of the opposite side. In the three
      consolidated cases, a spontaneous remodeling of the radiocarpal articular
      surfaces was noted. Graner's procedure is logical as it aims at creating a new
      radiocarpal articulation, either by the fusion of the lunate with the capitate
      (Graner I) or by replacing the lunate with the head of the capitate (Graner II
      and III). However, this old procedure should no longer be one of the surgical
      procedures for Kienbock disease due to its drawbacks: necrosis or non-union of
      the head of the capitate, necessity to perform a wrist fusion in the long-term
      and side effects of bone graft harvesting. LEVEL OF EVIDENCE: II. Retrospective
      study.

PMID- 24041804
TI  - Assembly of the Leishmania amazonensis flagellum during cell differentiation.
AB  - The flagellar cytoskeleton of Leishmania promastigotes contains the canonical 9+2
      microtubular axoneme and a filamentous structure, the paraflagellar rod (PFR),
      which is present alongside the axoneme. In contrast to promastigotes, which
      contain a long and motile flagellum, the amastigote form of Leishmania displays a
      short flagellum without a PFR that is limited to the flagellar pocket domain.
      Here, we investigated the biogenesis of the Leishmania flagellum at 0, 4, 6 and
      24h of differentiation. Light and electron microscopy observations of the early
      stages of L. amazonensis differentiation showed that the intermediate forms
      presented a short and wider flagellum that did not contain a PFR and presented
      reduced motion. 3D-reconstruction analysis of electron tomograms revealed the
      presence of vesicles and electron-dense aggregates at the tip of the short
      flagellum. In the course of differentiation, cells were able to adhere and
      proliferate with a doubling time of about 6h. The new flagellum emerged from the
      flagellar pocket around 4h after initiation of cell cycle. Close contact between
      the flagellar membrane and the flagellar pocket membrane was evident in the
      intermediate forms. At a later stage of differentiation, intermediate cells
      exhibited a longer flagellum (shorter than in promastigotes) that contained a PFR
      and electron dense aggregates in the flagellar matrix. In some cells, PFR
      profiles were observed inside the flagellar pocket. Taken together, these data
      contribute to the understanding of flagellum biogenesis and organisation during
      L. amazonensis differentiation. 

PMID- 24041805
TI  - Establishment and in vitro culture of porcine spermatogonial germ cells in low
      temperature culture conditions.
AB  - The objective of this study was to establish a porcine spermatogonial germ cell
      (pSGC) line and develop an in vitro culture system. Isolated total testicular
      cells (TTCs) from 5-day-old porcine testes were primary cultured at 31, 34, and
      37 degrees C. Although the time of colony appearance was delayed at 31 degrees C,
      strong alkaline phosphatase staining, expressions of pluripotency marker genes
      such as OCT4, NANOG, and THY1, and the gene expressions of the undifferentiated
      germ cell markers PLZF and protein gene product 9.5 (PGP9.5) were identified
      compared to 34 and 37 degrees C. Cell cycle analysis for both pSGC and feeder
      cells at the three temperatures revealed that more pSGCs were in the G2/M phase
      at 31 degrees C than 37 degrees C at the subculture stage. In vitro, pSGCs could
      stably maintain undifferentiated germ cell and stem cell characteristics for over
      60days during culture at 31 degrees C. Xenotransplantation of pSGCs to immune
      deficient mice demonstrated a successful colonization and localization on the
      seminiferous tubule basement membrane in the recipient testes. In conclusion,
      pSGCs from neonatal porcine were successfully established and cultured for long
      periods under a low temperature culture environment in vitro. 

PMID- 24041806
TI  - Oxidative stress causes DNA triplet expansion in Huntington's disease mouse
      embryonic stem cells.
AB  - Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded
      trinucleotide CAG repeat in the Huntingtin (Htt) gene. The molecular basis for
      the development and progression of HD is currently poorly understood. However,
      different DNA repair pathways have been implicated in both somatic expansion and
      disease progression. Embryonic stem cells provide a remarkable in vitro system to
      study HD and could have implications for understanding disease development and
      for therapeutic treatment. Here, we derive pluripotent stem cells from the mouse
      R6/1 HD model and demonstrate that repeated exposure to genotoxic agents inducing
      oxidative DNA damage gave a significant and dose dependent increase in somatic
      triplet expansion. Further investigation into specific steps of DNA repair
      revealed impaired double stranded break repair in exposed R6/1 cells, accompanied
      by the induction of apoptosis. We also found that differentiation status, and
      consequently DNA repair efficiency influenced somatic expansion. Our data
      underscore the importance of DNA damage and repair for the stability of the HD
      triplet in pluripotent stem cells. 

PMID- 24041807
TI  - Dyadic wavelet for image coding implementation on a Xilinx MicroBlaze processor:
      application to neutron radiography.
AB  - In this work, we present a mixed software/hardware implementation of 2-D signals
      encoder/decoder using dyadic discrete wavelet transform (DWT) based on quadrature
      mirror filters (QMF); using fast wavelet Mallat's algorithm. This work is
      designed and compiled on the embedded development kit EDK6.3i, and the synthesis
      software, ISE6.3i, which is available with Xilinx Virtex-IIV2MB1000 FPGA. Huffman
      coding scheme is used to encode the wavelet coefficients so that they can be
      transmitted progressively through an Ethernet TCP/IP based connection. The
      possible reconfiguration can be exploited to attain higher performance. The
      design will be integrated with the neutron radiography system that is used with
      the Es-Salem research reactor. 

PMID- 24041810
TI  - Clinical significance of immunogenicity in biologic therapy.

PMID- 24041811
TI  - Improvement for identification of heterophile antibody interference and AFP hook
      effect in immunoassays with multiplex suspension bead array system.
AB  - BACKGROUND: A variety of immunoassays including multiplex suspension bead array
      have been developed for tumor marker detections; however, these assays could be
      compromised in their sensitivity and specificity by well-known heterophile
      antibody interference and hook effect. METHODS: Using Luminex(r) multiplex
      suspension bead arrays, we modified protocols with two newly-developed solutions
      that can identify heterophile antibody interference and AFP hook effect.
      Effectiveness of the two solutions was assessed in serum samples from patients.
      RESULTS: Concentrations of 9 tumor markers in heterophile antibody positive
      samples assayed with Solution A, containing murine monoclonal antibodies and
      mouse serum, were significantly reduced when compared with those false high
      signals assayed without Solution A (all p<0.01). With incorporation of Solution H
      (fluorescent beads linked with AFP antigen), a new strategy for identification of
      AFP hook effect was established, and with this strategy AFP hook effect was
      identified effectively in serum samples with very high levels of AFP.
      CONCLUSIONS: Two proprietary solutions improve the identification of heterophile
      antibody interference and AFP hook effect. With these solutions, multiplex
      suspension bead arrays provide more reliable testing results in tumor marker
      detection where complex clinical serum samples are used.

PMID- 24041812
TI  - Interference from heterophilic antibodies in troponin testing. Case report and
      systematic review of the literature.
AB  - Heterophilic antibodies, comprising both "true" heterophilic antibodies and human
      anti-mouse antibodies (HAMA), represent an important source of interference in
      laboratory medicine, thus including cardiospecific troponin(s) testing. We
      describe the case of a 76-years-old woman with implausible and persistent
      elevation of cardiospecific troponin I, which was finally attributed to
      interference from heterophilic antibodies. According to literature data, the
      frequency of this interference ranges between 0.1 and 3.1%, is almost
      unpredictable and unsuspected, may involve both cardiospecific troponins I and T,
      and may virtually affect any type of immunoassay, either one- or two-step. The
      presence of interfering antibodies should always be suspected when test results
      do not go hand in hand with the clinics, or with the results of additional
      radiological and laboratory investigations. Once other causes of interference
      have been ruled out, test repetition with an alternative assay and removal of
      interfering antibodies with heterophilic antibodies blocking reagent, normal
      mouse serum, immobilized protein A column or polyethylene glycol may be
      advisable. As a simple alternative, measurement of serial dilutions of suspected
      samples usually shows nonlinearity of test results in the presence of
      heterophilic antibodies. 

PMID- 24041813
TI  - Behavior and well-being of extremely low birth weight teenagers in Iceland.
AB  - BACKGROUND: Preterm children are at risk for behavioral and emotional problems.
      AIMS: To evaluate behavior and emotional well-being of extremely low birth weight
      (ELBW) teenagers born in Iceland in 1991-1995. METHODS: Participants, 30 of 35
      ELBW survivors (25 girls, 5 boys, mean age 16.8 years), were interviewed,
      underwent medical examination and answered the Youth Self-Report for ages 11-18
      (YSR) of the Achenbach System of Empirically Based Assessment (ASEBA). The ELBW
      parents answered the ASEBA Child Behavior Checklist for ages 6-18 and the Autism
      Spectrum Screening Questionnaire (ASSQ). A comparison group of 30 teenagers (23
      girls, 7 boys, mean age 16.5 years) answered the YSR questionnaire and their
      parents answered the CBCL and ASSQ questionnaires. RESULTS: ELBW teenagers and
      parents report more behavior problems than the full term comparison teenagers and
      parents. They score significantly higher on the YSR and CBCL syndrome scales
      except for YSR and CBCL rule-breaking behavior and CBCL thought problems. The
      ELBW teenagers self-report on total competence, activities, social participation
      and academic performance was not significantly lower than the comparison
      teenagers. Parents of ELBW teenagers rated total competence, social participation
      and school performance of their children significantly lower than parents of
      comparison teenagers. The YSR Positive Qualities Scale was not significantly
      different between the two teenage groups. Two ELBW teenagers scored above cut-off
      points on the ASSQ questionnaire and none of the comparison teenagers. Bullying
      was reported by 20% of ELBW parents compared to none of the comparison group.
      CONCLUSION: ELBW teenagers experience emotional, behavior and social challenges.
      The teenagers value their positive qualities, activities and academic performance
      similar to peers.

PMID- 24041814
TI  - Validity and internal consistency of the Ages and Stages Questionnaire 60-month
      version and the effect of three scoring methods.
AB  - BACKGROUND: The Ages and Stages Questionnaire (ASQ) is currently the most used
      parent-completed developmental screener consisting of different age-specific
      questionnaires. Psychometric evaluation of the ASQ 60-month version (ASQ-60) is
      limited. Furthermore, it is unclear which of the available scoring methods of the
      ASQ is most useful in the identification of children with potential developmental
      problems. AIM: To evaluate the internal consistency and construct validity of the
      ASQ-60 with a large sample size, and to assess the effects of three scoring
      methods on this validity. STUDY DESIGN: Parents of 394 term-born and 1063 preterm
      born children from the prospective cohort-study Lollipop completed the ASQ-60 and
      a general questionnaire on school-problems. OUTCOME MEASURES: Internal
      consistency and construct validity of the ASQ-60 were determined using the ASQ
      total score. Construct validity was also determined using two other types of
      scoring-methods based on low domain-scores ('ASQ domain score') and parental
      concerns ('ASQ total score with parental concerns'). RESULTS: Cronbach's alpha
      for total score was 0.86, confirming internal consistency. Male gender,
      prematurity, low paternal education, low family income and small-for-gestational
      age were associated with low 'ASQ total scores,' confirming construct validity.
      Regarding construct validity with special education as criterion, sensitivity was
      best using the 'ASQ domain score' or the 'ASQ total score' with parental concerns
      (both 0.96). However, the specificity was best (0.93) using the ASQ total score.
      CONCLUSION: The ASQ-60 has a good internal consistency and validity to screen for
      developmental problems in the general population. The 'ASQ total score' has the
      best performance, the 'ASQ domain score' is recommended in case of preferred high
      sensitivity.

PMID- 24041815
TI  - Efficacy of Saccharomyces boulardii on necrotizing enterocolitis or sepsis in
      very low birth weight infants: a randomised controlled trial.
AB  - BACKGROUND: Probiotics have strain specific effects and the effects of fungi in
      preventing diseases in preterm infants have been investigated poorly.
      Saccharomyces boulardii is a yeast which acts both as a probiotic and a polyamine
      producer. AIM: The objective of this study was to investigate the efficacy of S.
      boulardii in preventing necrotizing enterocolitis (NEC) or sepsis in very low
      birth weight infants. STUDY DESIGN AND SUBJECTS: A prospective, double blind,
      placebo controlled trial was conducted in preterm infants (<= 32 GWs, <= 1500 g
      birth weight). They were randomized either to receive feeding supplementation
      with S. boulardii 50 mg/kg every 12 h or placebo, starting with the first feed
      until discharged. OUTCOME MEASURES: Necrotizing enterocolitis (NEC) or sepsis and
      NEC or death. RESULTS: Birth weight and gestational age of the study (n = 104)
      and the control (n = 104) groups were 1126 +/- 232 vs 1162 +/- 216 g and 28.8 +/-
      2.2 vs 28.7 +/- 2.1 weeks, respectively. Neither the incidence of stage >= 2 NEC
      or death nor stage >= 2 NEC or late onset culture proven sepsis was significantly
      lower in the study group when compared with the control group (9.6% vs 7.7%, p =
      0.62; 28.8% vs 23%, p = 0.34). Time to reach 100 mL/kg/day of enteral feeding
      (11.9 +/- 7 vs 12.6 +/- 7 days, p = 0.37) was not different between the groups.
      CONCLUSIONS: Saccharomyces boulardii did not decrease the incidence of NEC or
      sepsis.

PMID- 24041816
TI  - Fetal bacterial infections in antepartum stillbirth: a case series.
AB  - OBJECTIVES: This study aims to assess the frequency of fetal bacterial infections
      in stillbirth (SB) and to evaluate the best samples for the diagnosis of
      infection-related SB. STUDY DESIGN: Consecutive cases of antepartum SB were
      enrolled. Vaginal and placental swabs, as well as heart blood cultures and
      surface swabs from the neonate, were collected. Histological examinations were
      performed by the same examiner. Immunohistochemistry for leukocyte common antigen
      was performed in the placenta and fetus. Each case was discussed in a
      multidisciplinary audit. RESULTS: One hundred and nine cases were enrolled. Fetal
      blood cultures were positive in 20/95 cases (21%). Significant histological
      findings in the placenta/cord and in at least one fetal organ were observed in 8
      cases of them (4 Group B Streptococcus GBS, 2 Listeria monocytogenes, 1 Coagulase
      negative Staphylococcus, 1 Pseudomonas aeruginosa). Neither tissue damage nor
      inflammatory infiltrate was found in the 12 remnant cases. Funisitis while not
      histological chorioamnionitis was associated with microbiological findings.
      Positive findings in maternal/placental/fetal swabs occurred in 18-32% of cases
      with both negative fetal blood cultures and histopathological findings. With the
      exception of GBS, no other bacteria agent could be detected by any of the swabs.
      CONCLUSIONS: Eight cases (8.4%) fulfilled both microbiological and histology
      criteria allowing the diagnosis of SB-related fetal infection demonstrating that
      search for infections is essential in SB evaluation. Fetal blood culture,
      placenta swab for GBS and search for histological funisitis are mandatory actions
      within the SB work-up in order to guide pathology examination and reach clinical
      conclusions.

PMID- 24041817
TI  - Motor activity and intra-individual variability according to sleep-wake states in
      preschool-aged children with iron-deficiency anemia in infancy.
AB  - BACKGROUND: A chronic or acute insult may affect the regulatory processes that
      guide motor and behavioral performance, leading to increased intra-individual
      variability (IIV). Increased variability is often interpreted as an indication of
      regulatory dysfunction. Iron plays an important role in the regulatory processes
      of the nervous system and affects motor activity. To our knowledge, no study has
      examined the long-lasting patterns and IIV of motor activity following iron
      deficiency anemia in human infants. AIMS: This study compared 48-h motor activity
      and variability in preschool-aged children with or without iron-deficiency anemia
      (IDA) in infancy. METHODS: Motor activity was recorded through actigraphs during
      two week-days in 47 4-year-old Chilean children (23 former IDA and 24 non-anemic
      in infancy). All were given oral iron as infants. Sleep-wake states were
      identified by means of automated software. The frequency of movement units per
      minute was determined for each waking/sleep state during the individual day and
      night periods; data were examined in blocks of 15 min. Analyses of mean frequency
      and duration and intra-individual variability were conducted using multivariate
      mixed models. RESULTS: For daytime sleep, former IDA children were more active
      without a difference in the total duration. They also spent less time awake
      throughout the individual day period. Motor activity intra-individual variability
      was higher in former IDA children. CONCLUSIONS: The findings suggest that IDA in
      infancy sets the stage for long lasting dysfunction in the neural processes
      regulating sleep-wake states and spontaneous motor activity patterns.

PMID- 24041818
TI  - Ranking and selection of MII oocytes in human ICSI cycles using gene expression
      levels from associated cumulus cells.
AB  - STUDY QUESTION: Can the ranked expression levels of a cohort of cumulus cell (CC)
      genes be used to select MII oocytes with a potential for blastocyst development
      and live birth? SUMMARY ANSWER: A ranking method containing four (HAS2, FSHR,
      VCAN, PR) of the eight genes evaluated in this study for identifying good quality
      MII oocytes provides a significantly better outcome compared with random
      selection and is equally as good as using all oocytes for ICSI. WHAT IS KNOWN
      ALREADY: Recent evidence has identified a number of candidate genes in CC that
      have the potential to serve as markers of oocyte quality; however, a reliable
      method for selecting MII oocytes with blastocyst and live birth potential remains
      a challenge. STUDY DESIGN, SIZE, DURATION: A group of 25 patients (<38 years old)
      underwent rFSH-stimulated ICSI treatment with single embryo replacement (SET). A
      total of 270 cumulus cell-oocyte complexes (COCs) were recovered and assessed.
      MATERIALS, SETTING, METHODS: Expression levels of eight candidate genes (HAS2,
      FSHR, SLC2A4, ALCAM, SFRP2, VCAN, NRP1 and PR), corrected for RPL19, were
      measured in individual CC masses using multiplex QPCR. Expression levels of
      individual CC masses were assessed and ranked in relation to oocyte developmental
      indicators (blastocyst formation and live birth). MAIN RESULTS AND THE ROLE OF
      CHANCE: From the 25 women, 19 (76%) had achieved a successful live birth delivery
      following SET. In this population, the selection of MII oocytes according to
      relative ranking levels of a subset of CC-expressed genes provided a
      significantly higher chance of identifying a good quality oocyte compared with
      selecting MII oocytes randomly (blastocyst: 1* MII oocyte: 52 versus 23%, P =
      0.008; 3* MII oocytes: 80 versus 52%, P = 0.002; live birth: 1* MII oocyte: 31
      versus 15%, P<0.05, 3* MII oocytes: 60 versus 38%, P < 0.05) and a similar chance
      to that of using all oocytes available after recovery (blastocyst: 80% versus
      96%, P = 0.085, live birth: 60% versus 76%, P = 0.206). LIMITATIONS, REASONS FOR
      CAUTION: The present method was validated only for young (<38 years) women, with
      male infertility, who had no signs of androgenicity, PCOS or endometriosis and
      were free of any chronic disease. This is a retrospective study that requires
      further validation in an unselected population. WIDER IMPLICATIONS OF THE
      FINDINGS: Results presented in this study could be used to assist the selection
      of oocytes with high blastocyst developmental potential in frozen oocyte cycles
      and for the selection of embryos with high developmental potential as early as 18
      h after ICSI (2PN stage) in fresh human IVF cycles. STUDY FUNDING/COMPETING
      INTEREST(S): Funding was provided by Fertility Associates Ltd and the New Zealand
      Government. The authors declare there is no conflict of interest that could be
      perceived as prejudicing the impartiality of the research reported.

PMID- 24041819
TI  - Convenient synthesis of porous carbon nanospheres with tunable pore structure and
      excellent adsorption capacity.
AB  - A novel adsorbent, porous carbon nanosphere (PCNS), was conveniently prepared by
      the chemical activation of hydrothermally synthesized carbon nanosphere (CNS)
      with ZnCl2. The obtained PCNS materials were characterized by X-ray diffraction,
      Fourier transform infrared spectroscopy, N2 sorption technology and transmission
      electron microscope, and the results indicated that these materials possessed
      superior porosity with high surface area and large pore volume, in the meantime
      maintaining the nanospherical morphologies. Moreover, the porous structure of
      PCNS can be tuned from micropores to mesopores by adjusting the mass ratio of
      ZnCl2/CNS and the activation temperature. The porous structure endued PCNS
      excellent performance for the adsorption of bulky dyes from aqueous solution.
      Detailed adsorption behaviors of the optimized PCNS material, including
      adsorption isotherms and adsorption kinetics, were investigated. The experimental
      data of equilibrium adsorption capacity well matched Langmuir isotherms, and the
      maximum adsorption amounts of methylene blue, malachite green and rhodamine B
      were calculated as 3152, 1455 and 1409 mg g(-1), respectively, which were much
      higher than those of activated carbon and mesoporous carbon. The kinetic data
      were fitted to the models of pseudo-first-order and pseudo-second-order, which
      followed more closely the pseudo-second-order chemisorptions model. In addition,
      PCNS exhibited a good reusable property after five consecutive cycles.

PMID- 24041820
TI  - Microbial toxicity of the insensitive munitions compound, 2,4-dinitroanisole
      (DNAN), and its aromatic amine metabolites.
AB  - 2,4-Dinitroanisole (DNAN) is an insensitive munitions compound considered to
      replace conventional explosives such as 2,4,6-trinitrotoluene (TNT). DNAN
      undergoes facile microbial reduction to 2-methoxy-5-nitroaniline (MENA) and 2,4
      diaminoanisole (DAAN). This study investigated the inhibitory effect of DNAN,
      MENA, and DAAN toward various microbial targets in anaerobic (acetoclastic
      methanogens) and aerobic (heterotrophs and nitrifiers) sludge, and the
      bioluminescent bacterium, Aliivibrio fischeri, used in the Microtox assay.
      Aerobic heterotrophic and nitrifying batch experiments with DAAN could not be
      performed because the compound underwent extensive autooxidation in these assays.
      DNAN severely inhibited methanogens, nitrifying bacteria, and A. fischeri (50%
      inhibitory concentrations (IC50) ranging 41-57MUM), but was notably less
      inhibitory to aerobic heterotrophs (IC50>390 MUM). Reduction of DNAN to MENA and
      DAAN lead to a marked decrease in methanogenic inhibition (i.e., DNAN>MENA~DAAN).
      Reduction of all nitro groups in DNAN also resulted in partial detoxification in
      assays with A. fischeri. In contrast, reduction of a single nitro group did not
      alter the inhibitory impact of DNAN toward A. fischeri and nitrifying bacteria
      given the similar IC50 values determined for MENA and DNAN in these assays. These
      results indicate that reductive biotransformation could reduce the inhibitory
      potential of DNAN.

PMID- 24041821
TI  - Development of a model to predict the effect of water chemistry on the acute
      toxicity of cadmium to Photobacterium phosphoreum.
AB  - Cadmium (Cd) compounds are widely distributed toxic environmental and industrial
      pollutants, and they may bring danger to growth and development of aquatic
      organisms. The effects of Ca(2+) (as CaCl2), Mg(2+) (as MgSO4), K(+) (as KCl), pH
      and complexants (EDTA, the commercial DOM, and three homemade DOMs) on Cd
      toxicity to Photobacterium phosphoreum were evaluated in standardized 15 min
      acute toxicity tests. Increases in Ca(2+) concentration resulted in higher EC50
      values, indicating the competition between the two ions for uptake sites at the
      biotic ligand. Increased waterborne Mg(2+) also reduced Cd toxicity, but to a
      slightly lesser degree compared with Ca(2+). The overall decline in EC50 data
      with increasing K(+) in test solutions suggested that Cd toxicity was enhanced at
      larger K(+) concentration. The toxicity alleviation by H(+) was observed over the
      tested pH range of 5.0-9.0. Additions of complexing agents into the exposure
      water reduced Cd bioavailability via complexation of Cd(2+), and complexants from
      different sources displayed different protective effect. The influence of these
      toxicity modifying factors was finally incorporated into a model that can predict
      acute cadmidum toxicity for Photobacterium phosphoreum. After validation with
      laboratory and natural waters, the developed model could support efforts to
      improve the ecological relevance of presently applied risk assessment procedures.

PMID- 24041822
TI  - Mechanism of uranium(VI) uptake by Saccharomyces cerevisiae under environmentally
      relevant conditions: batch, HRTEM, and FTIR studies.
AB  - Biosorption is of significance for the safety evaluation of high-level nuclear
      wastes repositories and remediation of radioactive contamination places.
      Quantitive study and structural characterization of uranium uptake by both live
      and heat-killed Saccharomyces cerevisiae at environmentally relevant uranium
      concentration and with different ionic strengths were carried out. Kinetic
      investigation showed the equilibrium reached within 15 min. In equilibrium
      studies, pH shift towards neutral indicated release of hydroxyl ions. pH was the
      most important factor, which partly affected electrostatic interaction between
      uranyl ions and S. cerevisiae surface. The high ionic strength inhibited
      biosorption capacity, which can be explained by a competitive reaction between
      sodium ions and uranyl ions. Heat killing process significantly enhanced
      biosorption capacity, showing an order of magnitude higher than that of live
      cells. High resolution transmission electron microscopy (HRTEM) coupled with
      energy dispersive X-ray (EDX) showed needle-like uranium-phosphate precipitation
      formed on the cell walls for both live and heat-killed cells. Besides, dark-field
      micrographs displayed considerable similar uranium-phosphate precipitation
      presented outside the heat-killed cells. The phosphate released during heat
      killing process. FTIR illustrated function groups hydroxyl, carboxyl, phosphate,
      and amino groups played important role in complexation with uranium.

PMID- 24041823
TI  - Face mask ventilation--the dos and don'ts.
AB  - Face mask ventilation provides respiratory support to newly born or sick infants.
      It is a challenging technique and difficult to ensure that an appropriate tidal
      volume is delivered because large and variable leaks occur between the mask and
      face; airway obstruction may also occur. Technique is more important than the
      mask shape although the size must appropriately fit the face. The essence of the
      technique is to roll the mask on to the face from the chin while avoiding the
      eyes, with a finger and thumb apply a strong even downward pressure to the top of
      the mask, away from the stem and sloped sides or skirt of the mask, place the
      other fingers under the jaw and apply a similar upward pressure. Preterm infants
      require continuous end-expiratory pressure to facilitate lung aeration and
      maintain lung volume. This is best done with a T-piece device, not a self
      inflating or flow-inflating bag. 

PMID- 24041824
TI  - Cloning and transcriptional activity of ovarian-specific promoter in dairy goats.
AB  - Ovarian-specific promoter (OSP) is a tissue-specific promoter only expressed in
      the ovary to regulate its development. To investigate the activity of OSP in
      diverse dairy goat cells, OSP was cloned from dairy goat genome and used to
      construct the luciferase reporter vector pGL3-OSP to examine the transcriptional
      activity of OSP. Consequently, a 461-bp OSP fragment was obtained. Bioinformatics
      analysis indicated that the fragment contained multiple transcription factor
      binding sites, such as SRY, HSF, AP-1, C/EBP, CAAT, TATA, and so on, and the
      nucleotide sequence of OSP shared 99% and 97% similarity with those of OSP-1 and
      OSP-2 in rat. In addition, two variants were identified in the OSP (g.164T was
      deletion and g.375T<C). In diverse cells, the expression of luciferase in ovarian
      granulosa cells (GCs) and stromal cells of ovarian cortex was extremely
      significantly higher than that in fetal fibroblasts and oviduct epithelial cells.
      Meanwhile, the expression of luciferase in ovarian GCs was extremely
      significantly higher than that in the stromal cells of ovarian cortex. In
      summary, we successfully extracted dairy goat OSP and identified its
      transcriptional activity, which in part shed light on the study of ovarian
      specific transcription and provided further insights into the development and
      regulation of dairy goat's ovary as well. 

PMID- 24041825
TI  - Fertility in Angus cross beef cows following 5-day CO-Synch + CIDR or 7-day CO
      Synch + CIDR estrus synchronization and timed artificial insemination.
AB  - The present study determined whether a 5-day CO-Synch + controlled internal drug
      release (CIDR) protocol with two doses of PGF2alpha would improve timed
      artificial insemination (AI) pregnancy rate compared with 7-day CO-Synch + CIDR
      protocol in beef cows. Angus cross beef cows (N = 1817) at 12 locations were
      randomly assigned to 5-day CO-Synch + CIDR or 7-day CO-Synch + CIDR groups. All
      cows received 100 MUg of GnRH and a CIDR insert on Day 0. Cows (n = 911) in the 5
      day CO-Synch + CIDR group received two doses of 25 mg PGF, the first dose given
      on Day 5 at CIDR removal and the second dose 6 hours later, and 100 MUg GnRH on
      Day 8 and were inseminated concurrently, 72 hours after CIDR removal. Cows (n =
      906) in 7-day CO-Synch + CIDR group received 25 mg of PGF at CIDR removal on Day
      7, and 100 MUg GnRH on Day 10 and were inseminated concurrently, 66 to 72 hours
      after CIDR removal. All cows were fitted with a heat detector aid at CIDR removal
      and were observed twice daily until insemination for estrus and heat detector aid
      status. Accounting for estrus expression at or before AI (P < 0.0001) and body
      condition score (P < 0.01), cows in the 5-day CO-Synch + CIDR group had greater
      AI pregnancy rate compared with cows in the 7-day CO-Synch + CIDR group (58.1%
      vs. 55.1%; P = 0.04). More cows that exhibited estrus at or before AI became
      pregnant compared with cows that did not [65.7% (681/1037) vs. 44.5% (347/780); P
      < 0.0001]. The AI pregnancy rate was lesser for cows with body condition <=4 [<=4
      - 49.3% (101/219), 5-6 - 57.9%; >6 - 55.8%]. The mean AI pregnancy rate
      difference between treatment groups and projected economic outcome varied among
      locations. In conclusion, cows synchronized with the 5-day CO-Synch + CIDR
      protocol had greater AI pregnancy rate than those that received the 7-day CO
      Synch + CIDR protocol. 

PMID- 24041826
TI  - Effect of trehalose on DNA integrity of freeze-dried boar sperm, fertilization,
      and embryo development after intracytoplasmic sperm injection.
AB  - Freeze-drying (FD) medium containing ethylene glycol-bis(2-aminoethylether)
      N,N,N',N'-tetraacetic acid (EGTA) is reported to be beneficial for maintenance of
      sperm DNA integrity after FD. Recently, trehalose has also been reported to have
      notable ability to stabilize the protein structure and biomembranes of sperm in a
      dry state. In this study, we examined the effect of a combination of EGTA and
      different concentrations of trehalose in FD medium on sperm DNA integrity and the
      in vitro development of IVM porcine oocytes after intracytoplasmic sperm
      injection (ICSI) using freeze-dried boar sperm. Ejaculated sperm from a boar were
      suspended in basic FD medium supplemented with 0, 3.75, 7.5, 15, 30, 60, or 90 mM
      trehalose and freeze-dried. After rehydration, the sperm in all groups were
      subjected to DNA damage detection using a Halomax kit. It was found that the
      level of DNA damage in 15-mM group was significantly lower than that in 0-mM
      group, and no difference was observed between the 15-, 7.5-, and 3.75-mM groups.
      Moreover, there were no significant differences in the DNA damage level among 0,
      3.75 mM, and other groups treated with trehalose. When freeze-dried sperm were
      used for ICSI, the fertilization rates and blastocyst formation rates (observed
      at 10 hours and 6 days of IVC after ICSI, respectively) in the 7.5- and 15-mM
      groups were not different from those in 0-mM group. These results suggest that FD
      medium supplemented with trehalose at appropriate concentrations improves sperm
      DNA integrity, but does not improve fertilization and preimplantation embryo
      development of IVM oocytes following ICSI. 

PMID- 24041827
TI  - A new vulnerable population? The health of female partners of men recently
      released from prison.
AB  - BACKGROUND: Despite a growing literature on the consequences of having a romantic
      partner incarcerated on women's risk of contracting sexually transmitted
      infections, little research considers the broader health profile of the female
      partners of ever-imprisoned men. METHODS: We use data from the Relate Project (n
      = 332), a unique cross-sectional survey of recently released men and their female
      partners (2009-2011), to demonstrate that the female partners of recently
      released men suffer from a variety of health risks and conditions. We also
      examine the health conditions of females by their own incarceration history.
      FINDINGS: We find that these women engage in poor health behaviors including
      smoking, drug use, and excessive alcohol consumption and have high levels of
      health conditions including asthma, hypertension, anxiety, and depression. The
      vulnerability of women who had themselves been incarcerated in jails or prisons
      was especially acute. The number of risky background characteristics such as
      dropping out of high school (45%) and spending time in foster care or a group
      home (36%) were staggeringly high for ever-imprisoned women, as were their rates
      of anxiety (50%), depression (59%), and posttraumatic stress disorder (45%).
      CONCLUSIONS: Results reveal that the health of the female partners of recently
      released men is at least as poor as that of their male partners, suggesting a
      degree of vulnerability that has yet to be considered in the medical or public
      health literature and a population that desperately needs medical attention with
      the full rollout of the Affordable Care Act in 2014.

PMID- 24041828
TI  - The influence of personal and group racism on entry into prenatal care among
      African American women.
AB  - BACKGROUND: Racism has been hypothesized as a barrier to accessing health care.
      No quantitative study has directly assessed its influence on women's initiation
      of prenatal care (PNC). We examined the relationship between PNC entry and
      experiences of personal and group racism among low-income, African-American (AA)
      women. We also examined whether the use of denial of racism as a coping mechanism
      was associated with a delay in accessing PNC. METHODS: Using a
      prospective/retrospective cohort design we collected data from 872 AA women
      (prenatally, n = 484; postpartum, n = 388). Multinomial logistic regression was
      used to assess the relationship between the overall denial of racism index and
      PNC initiation. FINDINGS: PNC entry was not associated with personal experiences
      of racism (p = .33); it was significantly associated with group experiences (p <
      .01). CONCLUSION: Denial of racism experienced by other AAs was a barrier to
      early PNC among low-income, AA women. Delayed access to PNC may be rooted in the
      avoidance of racialized experiences among less empowered women when faced with
      discrimination. Our findings have important implication for the engagement of AA
      women into the PNC delivery system and the health care system postpartum.

PMID- 24041829
TI  - Muscle-specific kinase antibody positive myaesthenia gravis and multiple
      sclerosis co-presentation: a case report and literature review.
AB  - We present the first case of simultaneous muscle-specific kinase antibody
      positive myaesthenia gravis and relapsing-remitting multiple sclerosis to be
      reported in the English literature along with the inherent diagnostic and
      treatment challenges. There may be an association between myaesthenia and central
      nervous system demyelination. We identified 72 previously published cases of
      myaesthenia with central nervous system demyelination. Of 19 cases of myaesthenia
      with relapsing-remitting multiple sclerosis, nine (47%) were acetylcholine
      receptor antibody negative, but there were no previously published cases with
      muscle-specific kinase antibody. Further research is required to clarify this
      association and optimal treatment in such cases. 

PMID- 24041830
TI  - Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating
      polypeptide (PACAP) in humans with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central
      nervous system that leads to demyelination and neurodegeneration. VIP and PACAP
      are structurally related neuropeptides with neuroprotective and anti-inflammatory
      activities. To evaluate VIP and PACAP-38 in plasma and CSF in humans in
      correlation with IL-6, IL-10 and TNFalpha, we compared 20 MS individuals with 27
      healthy controls. In MS, a decrease in PACAP-38 in CSF and a decrease in plasma
      IL-6 concentration were seen. A positive correlation between plasma VIP and
      plasma IL-6 was identified. We conclude that VIP and PACAP may influence the
      course of MS. 

PMID- 24041831
TI  - Complement-mediated muscle cell lysis: a possible mechanism of myonecrosis in
      anti-SRP associated necrotizing myopathy (ASANM).
AB  - The mechanism of necrotizing myopathy associated with antibodies to signal
      recognition particle (SRP) remains unclear. We investigated the effect of anti
      SRP+serum and complement on cell viability in myoblast cultures. Cell viability
      was only slightly reduced by incubation with anti-SRP+serum compared with control
      serum. However, the addition of fresh complement resulted in a marked reduction
      in cell survival. Surface immunostaining for SRP, C3c and C5b-9 was demonstrated
      in cultures pre-incubated with anti-SRP+serum and complement, and in muscle
      biopsies from patients with myopathy. These findings provide further support for
      a complement-dependent antibody-mediated mechanism in anti-SRP associated
      myopathy. 

PMID- 24041832
TI  - Improving disclosure and management of medical error - an opportunity to
      transform the surgeons of tomorrow.
AB  - INTRODUCTION: Human error is the major causal factor of industrial and
      transportation accidents and healthcare is not immune to the effects of human
      error. Medical error can be defined as the failure of the planned action to be
      completed as intended or the use of a wrong plan to achieve an aim. AIM: The
      objective of this literature review was to explore the practices of medical error
      management and disclosure by surgical trainees and to examine how to better
      prepare and educate the surgeons of tomorrow. METHODS: PubMed was searched to
      identify available literature. Preliminary search criteria included medical error
      and junior doctors, management and prevention of medical error. RESULTS: Fifty
      two papers were included for review. Medical error is common and junior doctors
      are more vulnerable to err. Most serious errors occur in the emergency
      department, operating rooms and the intensive care unit. Improvements in patient
      safety result primarily from organizational and individual learning, particularly
      with reference to trainee doctors who present an enhanced level of risk.
      CONCLUSION: Junior doctors are a unique population, with a higher propensity to
      medical error. A transition from the current culture of 'name, blame and shame'
      is required. We need to ensure that the 'learning moment' is seized and that
      mistakes are learned from and not simply forgotten. Surgery has an opportunity to
      learn from high risk-industries and incorporate human factors training, into
      surgical training programs in order to better manage and prevent medical error.

PMID- 24041833
TI  - Tetracoding increases with body temperature in Lepidosauria.
AB  - Codons expanded by a silent position (quadruplet or tetracodons) may solve the
      conundrum that at life's origins, the weak tricodon-anticodon interactions could
      not promote translation in the absence of complex ribosomes. Modern genomes have
      isolated tetracodons resulting from insertion mutations. Some bioinformatic
      analyses suggest that tetracoding stretches overlap with regular mitochondrial
      protein coding genes. These tetragenes are probably decoded by (antisense) tRNAs
      with expanded anticodons. They are GC-rich, which produce stronger basepairs than
      A:T interactions, suggesting expression at high temperatures. The hypothesis that
      tetracoding is an adaptation to high temperatures is tested here by comparing
      predicted mitochondrial tetracoding in Lepidosauria (lizards, amphisbaenia, and
      Sphenodon), in relation to body temperature, expecting more tetracoding in
      species with high body temperature. The association between tRNAs with expanded
      anticodons and tetracoding previously described for mammals and Drosophila is
      confirmed for Lepidosauria. Independent evidence indicates that tetracoding
      increases with body temperature, supporting the hypothesis that tetracoding is an
      adaptation for efficient translation when conditions (temperature) make triplet
      codon-anticodons too unstable to allow efficient protein elongation. 

PMID- 24041834
TI  - Modalities of memory: is reading lips like hearing voices?
AB  - Functional similarities in verbal memory performance across presentation
      modalities (written, heard, lipread) are often taken to point to a common
      underlying representational form upon which the modalities converge. We show here
      instead that the pattern of performance depends critically on presentation
      modality and different mechanisms give rise to superficially similar effects
      across modalities. Lipread recency is underpinned by different mechanisms to
      auditory recency, and while the effect of an auditory suffix on an auditory list
      is due to the perceptual grouping of the suffix with the list, the corresponding
      effect with lipread speech is due to misidentification of the lexical content of
      the lipread suffix. Further, while a lipread suffix does not disrupt auditory
      recency, an auditory suffix does disrupt recency for lipread lists. However, this
      effect is due to attentional capture ensuing from the presentation of an
      unexpected auditory event, and is evident both with verbal and nonverbal auditory
      suffixes. These findings add to a growing body of evidence that short-term verbal
      memory performance is determined by modality-specific perceptual and motor
      processes, rather than by the storage and manipulation of phonological
      representations. 

PMID- 24041835
TI  - Children's developing understanding of the relation between variable causal
      efficacy and mechanistic complexity.
AB  - Two experiments investigated 3-4-year-olds' ability to infer the causal
      mechanisms for a pair of lights. In both experiments the exterior of the two
      lights appeared identical. In Experiment 1, one light displayed a stable
      activation pattern of a single color while the other light displayed a variable
      pattern of activation by cycling through a series of different colors (i.e., a
      more varied effect). Children were asked to judge which light had a more complex
      internal structure. Four-year-olds were more likely to match the light with the
      more variable effect with a more complex internal mechanism and the light with
      the more stable effect with a less complex mechanism. Three-year-olds' responses
      were at chance. Experiment 2 replicated this finding when the activation patterns
      of the two lights were described verbally but never demonstrated. Taken together,
      these results suggest that 4-year-olds appreciate that the variability of an
      object's causal efficacy is related to the complexity of its internal mechanistic
      structure. 

PMID- 24041836
TI  - Fooled by the brain: re-examining the influence of neuroimages.
AB  - A series of highly-cited experiments published in 2008 demonstrated a biasing
      effect of neuroimages on lay perceptions of scientific research. More recent
      work, however, has questioned this bias, particularly within legal contexts in
      which neuroscientific evidence is proffered by one of the parties. The present
      research moves away from the legal framework and describes five experiments that
      re-examine this effect. Experiments 1 through 4 present conceptual and direct
      replications of some of the original 2008 experiments, and find no evidence of a
      neuroimage bias. A fifth experiment is reported that confirms that, when
      laypeople are allowed multiple points of reference (e.g., when directly comparing
      neuroimagery to other graphical depictions of neurological data), a neuroimage
      bias can be observed. Together these results suggest that, under the right
      conditions, a neuroimage might be able to bias judgments of scientific
      information, but the scope of this effect may be limited to certain contexts. 

PMID- 24041837
TI  - How do we convert a number into a finger trajectory?
AB  - How do we understand two-digit numbers such as 42? Models of multi-digit number
      comprehension differ widely. Some postulate that the decades and units digits are
      processed separately and possibly serially. Others hypothesize a holistic process
      which maps the entire 2-digit string onto a magnitude, represented as a position
      on a number line. In educated adults, the number line is thought to be linear,
      but the "number sense" hypothesis proposes that a logarithmic scale underlies our
      intuitions of number size, and that this compressive representation may still be
      dormant in the adult brain. We investigated these issues by asking adults to
      point to the location of two-digit numbers on a number line while their finger
      location was continuously monitored. Finger trajectories revealed a linear scale,
      yet with a transient logarithmic effect suggesting the activation of a
      compressive and holistic quantity representation. Units and decades digits were
      processed in parallel, without any difference in left-to-right vs. right-to-left
      readers. The late part of the trajectory was influenced by spatial reference
      points placed at the left end, middle, and right end of the line. Altogether,
      finger trajectory analysis provides a precise cognitive decomposition of the
      sequence of stages used in converting a number to a quantity and then a position.

PMID- 24041838
TI  - Emotion and memory: a recognition advantage for positive and negative words
      independent of arousal.
AB  - Much evidence indicates that emotion enhances memory, but the precise effects of
      the two primary factors of arousal and valence remain at issue. Moreover, the
      current knowledge of emotional memory enhancement is based mostly on small
      samples of extremely emotive stimuli presented in unnaturally high proportions
      without adequate affective, lexical, and semantic controls. To investigate how
      emotion affects memory under conditions of natural variation, we tested whether
      arousal and valence predicted recognition memory for over 2500 words that were
      not sampled for their emotionality, and we controlled a large variety of lexical
      and semantic factors. Both negative and positive stimuli were remembered better
      than neutral stimuli, whether arousing or calming. Arousal failed to predict
      recognition memory, either independently or interactively with valence. Results
      support models that posit a facilitative role of valence in memory. This study
      also highlights the importance of stimulus controls and experimental designs in
      research on emotional memory. 

PMID- 24041839
TI  - Diagnostic utility of magnetic resonance imaging and magnetic resonance
      angiography in the radiological evaluation of pulsatile tinnitus.
AB  - AIM: Our aim was to assess the diagnostic utility of magnetic resonance imaging
      with complimentary magnetic resonance angiography (MRI/MRA) in the radiological
      evaluation of patients with pulsatile tinnitus (PT). MATERIALS AND METHODS: The
      present study was retrospectively conducted on 27 patients with pulsatile
      tinnitus. All patients showed normal otoscopic findings and were evaluated with
      magnetic resonance imaging (MRI) with complimentary magnetic resonance
      angiography (MRA), 9/27 (33.3%) patients were investigated by CT, and 12/27
      (44.4%) were evaluated by angiography. All patients' clinical investigation was
      reviewed to discard systemic causes of PT. RESULTS: All hard copies of MRI/MRA
      studies were evaluated. MRI/MRA detected the underlying etiology of subjective
      pulsatile tinnitus (PT) in 11/27 patients (40.7%), and 16/27 patients (59.5%)
      showed normal MRI/MRA examination. The most common cause was dural arteriovenous
      malformation (AFM) in 4/27 (14.8%) patients, high jugular bulbus in 2/27 (7.4%),
      aneurysm of internal carotid artery in 1/27 (3.7%), aberrant internal carotid
      artery in 1/27 (3.7%), vertebral artery hypoplasia in 2/27 (7.4%), and glomus
      tumor in 1/27 (3.7%). The statistical results of the present study showed that
      MRI/MRA had the following: 80% sensitivity, 88% specificity, 86% accuracy, 85%
      PPV, 83% NPV, and 15% error percentage for diagnosis of PT. CONCLUSION: MRI/MRA
      was an effective radiological imaging method in detecting the underlying
      pathology of pulsatile tinnitus. Magnetic resonance may be considered a first
      line diagnostic imaging modality in the assessment of subjective pulsatile
      tinnitus.

PMID- 24041840
TI  - The presence of hepatitis B core antibody is associated with more advanced liver
      disease in alcoholic patients with cirrhosis.
AB  - BACKGROUND: Liver disease is more severe in patients with chronic hepatitis B
      virus (HBV) infections and alcohol-induced liver injury. Whether the same is true
      for alcoholic patients with cirrhosis who have recovered from previous HBV
      infections remains to be determined. OBJECTIVES: To document the extent of liver
      disease in alcoholic patients with cirrhosis who test negative for hepatitis B
      surface antigen (HBsAg) and test positive for antibody to hepatitis B core
      antigen (anti-HBc). METHODS: Two hundred fifty-four alcoholic patients with
      cirrhosis were divided into anti-HBc-positive (N = 171) and anti-HBc-negative (N
      = 83) cohorts. Demographic, clinical, and biochemical features were
      retrospectively analyzed. Prognostic scores and the prevalence of patients at
      high risk for short-term mortality were calculated. Logistic regression was used
      to identify factors associated with an increased risk for short-term mortality.
      RESULTS: Jaundice was more common in the anti-HBc-positive cohort (32.2% vs.
      18.1%, p = 0.02). This cohort also had higher serum bilirubin (70.9 vs. 50.4
      MUM/L, p = 0.03), prothrombin times (15.6 vs. 14.4 s, p = 0.01), MELD scores (8.5
      vs. 4.6, p = 0.01), i-MELD scores (28.6 vs. 24.7, p = 0.03), MDF scores (14.2 vs.
      6.8, p = 0.02) and ABIC scores (7.2 vs. 6.6, p = 0.01). In addition, anti-HBC
      positive patients were more often at high risk for short-term mortality (40.4%
      vs. 26.5%, p = 0.03). Multivariate analysis identified anti-HBc-positive status
      (OR: 1.84; 95% CI: 1.10-3.36) and alcohol intake >=150 g/day (OR: 2.01; 95% CI:
      1.10-3.66) as independent risk factors for high risk of mortality. CONCLUSION:
      The anti-HBc-positive state is associated with more advanced liver disease in
      alcoholic patients with cirrhosis. A prospective study including HBV-DNA testing
      and liver biopsies should be considered to validate and further elucidate these
      findings.

PMID- 24041841
TI  - [Presence of anti-SRP and anti-M2 antibodies in patients with severe
      polymyositis].

PMID- 24041842
TI  - Molecular cloning and characterization of a cathepsin B gene from the Chinese
      shrimp Fenneropenaeus chinensis.
AB  - Cathepsin B is a unique member of the cathepsin superfamily, which acts as both
      an endopeptidase and peptidyl-dipeptidase. To obtain a better understanding of
      this enzyme, we cloned a cDNA encoding cathepsin B from the muscle of
      Fenneropenaeus chinensis (FcCB). FcCB contained a 996-bp open reading frame (ORF)
      encoding a protein of 331 amino acid residues with a putative signal peptide and
      a propeptide_C1 at the N-terminal, a glutamine oxyanion hole and active site
      cysteine, histidine and asparagine residues. A region from residue 79 to 327
      conferred the peptidase activity of FcCB. Pair-wise and multiple sequence
      alignment with 17 other organisms, including ten different vertebrate species,
      five different invertebrate species and two different plant species, indicated
      that the signal peptide and the propeptide_C1 at the N-terminal of FcCB were less
      conserved than the mature protein, except when compared with Penaeus monodon,
      Litopenaeus vannamei and Marsupenaeus japonicas, all of which belong to the genus
      Penaeus. The expression of FcCB in the hepatopancreas was higher than that in the
      gill. The expression of FcCB in the gill was higher than that in the muscle. A
      challenge test was performed to reveal the responses of FcCB in different tissues
      to white spot syndrome virus (WSSV) infection, which causes serious economic
      losses in the shrimp farming industry. The FcCB gene expressions in the ectoderm,
      mesoderm and entoderm were not the same prior to WSSV infection, but at 6 h after
      WSSV challenge, the FcCB expression in the gill, hepatopancreas and muscle was up
      regulated, suggesting that FcCB might be involved in the immune response to WSSV.
      Three single nucleotide polymorphisms (SNPs) were identified in the FcCB gene,
      involving C/T transitions, which are known as mutation hot spots. Notably, the
      three SNPs constituted a haplotype that can be used as an indicator of the
      haplotype block. The SNP genotypes of two groups of shrimps, respectively
      comprising 96 WSSV-resistant shrimps and 96 WSSV-susceptible shrimps, were
      obtained using a high-resolution melting (HRM) method. Associated factors,
      including observed heterozygosity (Ho), expected heterozygosity (He), minor
      allele frequency (MAF) and P-values for the deviation from Hardy-Weinberg
      equilibrium (HWE), were obtained. For the association analysis with WSSV
      resistance, the P-values were calculated using Pearson's chi-square test. In the
      two groups, the MAFs of all sites were greater than 0.05, and no site departed
      significantly (P < 0.05) from HWE. The genotype distribution of the C-984T
      mutation site between the two groups was not significantly different. These
      results lead to a better understanding of the molecular mechanisms of the host
      virus interaction and provide useful information for solving the WSSV problem.

PMID- 24041843
TI  - Lactococcus lactis BFE920 activates the innate immune system of olive flounder
      (Paralichthys olivaceus), resulting in protection against Streptococcus iniae
      infection and enhancing feed efficiency and weight gain in large-scale field
      studies.
AB  - The protective effect of a food-grade lactic acid bacterium Lactococcus lactis
      BFE920 against disease of olive flounder (Paralichthys olivaceus) cultivated on a
      large scale was studied. Initially, antimicrobial activity of L. lactis against
      several fish pathogens was evaluated in vitro; the probiotic showed strong
      antibacterial activity against Streptococcus iniae, Streptococcus parauberis and
      Enterococcus viikkiensis, and moderate activity against Lactococcus garviae. When
      olive flounders were fed for two weeks with experimental diets containing varying
      concentrations of L. lactis (1 * 10(6), 5 * 10(6), 2.5 * 10(7) and 1.25 * 10(8)
      CFU/g feed), all the experimental feed groups showed 68-77% survival upon
      challenge with S. iniae. A field-scale feeding trial with L. lactis dietary
      supplement was conducted in a local fish farm (n = 12,000) for three months, and
      disease resistance, innate immune parameters and growth performance were
      evaluated. The average weight gain and feed efficiency were increased up to 6.8%
      and 8.5%, respectively. At the end of the feeding trial, the olive flounders were
      challenged with S. iniae. The L. lactis-fed group was protected from S. iniae
      challenge with a 66% survival rate. This disease protection is due to the
      flounder's innate immunity activated by the L. lactis administration: increased
      lysosomal activities and production of IL-12 and IFN-gamma. These data clearly
      indicated that L. lactis BFE920 may be developed as a functional feed additive
      for protection against diseases, and for enhancement of feed efficiency and
      weight gain in olive flounder farming.

PMID- 24041844
TI  - The effect of oyster mushroom beta-1.3/1.6-D-glucan and oxytetracycline
      antibiotic on biometrical, haematological, biochemical, and immunological
      indices, and histopathological changes in common carp (Cyprinus carpio L.).
AB  - The aim of the study was to evaluate the effect of micronized beta-1.3/1.6-D
      glucan (BG) derived from the oyster mushroom Pleurotus ostreatus Hiratake and
      tetracycline antibiotic oxytetracycline (OTC) on biometrical, haematological,
      biochemical, and immunological indices, and histopathological changes in tissues
      of one- to two-year-old common carp (Cyprinus carpio L.). The fish tested were
      divided into five experimental groups and one control. Carp in the control group
      were fed commercial carp feed pellets. Fish in the five experimental groups were
      fed the same pellets supplemented with either OTC, a combination of OTC and BG,
      or BG as follows: 75 mg oxytetracycline kg(-1) bw (OTC group), 75 mg
      oxytetracycline kg(-1) bw and 0.5% beta-glucan (OTC + 0.5% BG group), 75 mg
      oxytetracycline kg(-1) bw and 2.0% beta-glucan (OTC + 2.0% BG group), 0.5% beta
      glucan (0.5% BG group), and 2.0% beta-glucan (2.0% BG group). OTC- and BG
      supplemented diets and the control diet were administered to experimental and
      control carp for 50 days (i.e. samplings 1-3, the exposure period); for the
      following 14 days, fish were fed only control feed pellets with no OTC or BG
      supplementation (i.e. sampling 4, the recovery period). Blood and tissue samples
      were collected both during, and at the end of the study. No significant changes
      in biometrical indices (i.e. total length, standard length, total weight,
      hepatosomatic and spleen somatic index, and Fulton's condition factor) were found
      in experimental carp compared to control in any sampling. In haematological
      indices, significant changes were found only in sampling 2, in which shifts in
      PCV (P < 0.01), Hb (P < 0.01), and WBC (P < 0.01), and in the counts of
      lymphocytes (P < 0.01), monocytes (P < 0.01), and neutrophil granulocytes
      segments (P < 0.05) were revealed. As for biochemical profiling, plasma
      concentrations of glucose, albumins, cholesterol, natrium, and chlorides (all P <
      0.01), and total proteins, lactate, phosphorus, and potassium (all P < 0.05) as
      well as the catalytic activity of ALP (P < 0.05) were altered in common carp. A
      significant change in induced (opsonizedzymosan particles, OZP) chemiluminescence
      (P < 0.05) in sampling 3 and no shifts in serum immunoglobulins concentration
      were found in the immunological analysis. Histopathological examination of skin,
      gills, liver, spleen, and cranial and caudal kidneys revealed no obvious specific
      changes in any tissue analysed. The use of beta-glucans in clinically healthy
      aquaculture remains an issue. Nevertheless, their use in breeding endangered by
      stress stimuli, infectious disease, or adverse environmental factors is
      defensible.

PMID- 24041845
TI  - Do general practitioners follow treatment recommendations from guidelines in
      their decisions on heart failure management? A cross-sectional study.
AB  - OBJECTIVE: To investigate whether general practitioners (GPs) follow treatment
      recommendations from clinical practice guidelines in their decisions on the
      management of heart failure patients, and assess whether doctors' characteristics
      are related to their decisions. DESIGN: Cross-sectional vignette study. SETTING:
      Continuing Medical Education meeting. PARTICIPANTS: 451 Dutch GPs. MAIN OUTCOME
      MEASURES: Answers to four multiple-choice treatment decisions in clinical
      vignettes of a patient with heart failure and a reduced ejection fraction. With
      univariable and multivariable regression analyses, respondent characteristics
      were related to optimal treatment decisions. RESULTS: Of the 451 GPs, none took
      four optimal decisions: 7% considered stopping statin treatment, 36% initiated
      beta-blocker treatment at a low-dose and 4% doubled the beta-blocker in the up
      titration phase. Finally, for our vignette patient now also suffering from
      chronic obstructive pulmonary disease, 45% of the GPs continued beta-blocker
      therapy even when they considered prescribing a long-acting beta2-agonist. While
      the relation between respondent characteristics and each decision was very
      different, none was independently associated with all four decisions. Giving
      priority to evidence-based medicine was independently related to stopping statin
      treatment and doubling the beta-blocker in the up-titration phase. CONCLUSIONS:
      GPs seem not to follow treatment recommendations from clinical practice
      guidelines in their decisions on the management of heart failure patients. The
      recommendations from guidelines may appear counterintuitive when statin treatment
      needs to be stopped when a patient feels comfortable, or when a beta-blocker
      should be up-titrated in patients who experience more symptoms. Giving priority
      to evidence-based medicine is possibly positively related to difficult treatment
      decisions.

PMID- 24041846
TI  - Internet-based hearing screening using speech-in-noise: validation and
      comparisons of self-reported hearing problems, quality of life and phonological
      representation.
AB  - OBJECTIVES: For the last decade a host of different projects have been launched
      to allow persons who are concerned about their hearing status to quickly and at a
      low cost test their hearing ability. Most often, this is carried out without
      collecting complementary information that could be correlated with hearing
      impairment. In this two-part study we first, present the development and
      validation of a novel Internet-based hearing test, and second, report on the
      associations between this test and phonological representation, quality of life
      and self-reported hearing difficulties. DESIGN: Cross-sectional study. SETTING:
      An opportunity sample of participants was recruited at the Stockholm central
      station for the first study. All parts of the second study were conducted via the
      Internet, with testing and self-report forms adapted for online use.
      PARTICIPANTS: The first part of the study was carried out in direct contact with
      the participants, and participants from the second study were recruited by means
      of advertisements in newspapers and on webpages. The only exclusion criterion was
      that participants had to be over 18 years old. Most participants were between 60
      and 69 years old. There were almost an equal number of men and women (total
      n=316). OUTCOME MEASURES: 48 participants failed the Internet-based hearing
      screening test. The group failing the test reported more problems on the
      Amsterdam Inventory of Auditory Disability. In addition, they were found to have
      diminished phonological representational skills. However, no difference in
      quality of life was found. CONCLUSIONS: Almost one in five participants was in
      need of contacting their local hearing clinic. This group had more complaints
      regarding tinnitus and hyperacusis, rated their own hearing as worse than those
      who passed, and had a poorer capability of generating accurate phonological
      representations. This study suggests that it is feasible to screen for hearing
      status online, and obtain valid data.

PMID- 24041847
TI  - Maternal body mass index and duration of labor.
AB  - OBJECTIVE: To evaluate whether the duration of the active phase of labor is
      associated with maternal body mass index (BMI), in nulliparous women with
      spontaneous onset of labor. STUDY DESIGN: Historical prospective cohort study
      including 63,829 nulliparous women with a singleton pregnancy and a spontaneous
      onset of labor, who delivered between January 1, 1995 and December 31, 2009. Data
      were collected from the Perinatal Revision South registry, a regional perinatal
      database in Southern Sweden. Women were categorized into six classes of BMI.
      Overweight and obese women were compared to normal weight women regarding
      duration of active labor. Adjustments were made for year of delivery, maternal
      age and infant birth weight. RESULTS: The median duration of labor was
      significantly longer in obese women (class I obesity (BMI 30-34.9) = 9.1h, class
      II obesity (BMI 35-39.9) = 9.2h and class III obesity (BMI > 40) = 9.8h) compared
      to normal-weight women (BMI 18.5-24.9) = 8.8h (p < 0.001). The risk of labor
      lasting more than 12h increased with increasing maternal BMI: OR 1.04 (1.01-1.06)
      (OR per 5-units BMI-increase).The risk of labor lasting more than 12h or
      emergency cesarean section within 12h, compared to vaginal deliveries within 12h,
      increased with increasing maternal BMI. Duration of the second stage of labor was
      significantly shorter in obese women: in class III obesity the median value was
      0.45 h compared to normal weight women, 0.55 h (p < 0.001). CONCLUSION: In
      nulliparous women with a spontaneous onset of labor, duration of the active phase
      of labor increased significantly with increasing maternal BMI. Once obese women
      reach the second stage they deliver more quickly than normal weight women, which
      implies that the risk of prolonged labor is restricted to the first stage of
      labor. It is clinically important to consider the prolonged first stage of labor
      in obese women, for example when diagnosing first stage labor arrest, in order to
      optimize management of this rapidly growing at-risk group of women. Thus, it
      might be reasonable to adapt the considered upper limit for duration of labor,
      according to maternal BMI.

PMID- 24041848
TI  - NOD1 expression elicited by iE-DAP in first trimester human trophoblast cells and
      its potential role in infection-associated inflammation.
AB  - OBJECTIVES: The underlying mechanisms of protective immunity of placental
      trophoblast cells against bacterial infection remain largely unknown. NOD1 are
      intracellular pattern recognition receptors that are activated by bacterial
      peptides and mediate innate immunity. This study aimed to investigate the
      expression and function of NOD1 in first trimester trophoblast cells, and
      evaluate the potential role of trophoblast cells in infection-associated
      inflammation. STUDY DESIGN: Human extravillous trophoblast cell line HTR8 cells
      were stimulated with various concentrations of iE-DAP for various periods of
      time. NOD1 expression was detected by immunofluorescence, and the changes in NOD1
      and RICK mRNA and protein in H8 cells were determined by real-time polymerase
      chain reaction and Western blot analysis. The concentrations of interleukin (IL)
      8 and IL-6 secreted by H8 cells were examined by enzyme-linked immunosorbent
      assay. NF-kappaB transcription activity and P65 expression were detected by
      electrophoretic mobility shift assay and Western blot analysis. RESULTS: H8 cells
      expressed NOD1, and the effects of iE-DAP on NOD1 were dose- and time-dependent.
      The concentration of IL-8 increased gradually with increasing concentration of iE
      DAP, and the levels of IL-8 and IL-6 were associated with the duration of
      exposure to iE-DAP. The dose of iE-DAP was significantly associated with
      expression of RICK and P65, and stimulation of H8 cells by iE-DAP altered NF
      kappaB transcription activity. CONCLUSIONS: NOD1 may have a role in mediating
      infection-associated inflammation. Once iE-DAP is recognized by NOD1, the
      inflammatory response may be induced via NOD1-RICK-NF-kappaB-mediated pathways.

PMID- 24041849
TI  - Perceptual dominance during binocular rivalry is prolonged by a dynamic surround.
AB  - We examined whether dynamic stimulation that surrounds a rival target influences
      perceptual alternations during binocular rivalry. We presented a rival target
      surrounded by dynamic random-dot patterns to both eyes, and measured dominance
      durations for each eye's rival target. We found that rival target dominance
      durations were longer when surrounds were dynamic than when they were static or
      absent. Additionally, prolonged dominance durations were more apparent when the
      dynamic surround was alternately presented between the two eyes than when it was
      presented simultaneously to both eyes. These results indicate that dynamic
      stimulation that surrounds a rival target plays a role in maintaining the current
      perceptual state, and causes less perceptual alternations during binocular
      rivalry. Our findings suggest that dynamic signals on the retina may suppress
      rivalry, and thus provide useful information for stabilizing perceptions in daily
      life. 

PMID- 24041850
TI  - Photoinduced antibacterial activity of two dicationic 5,15-diarylporphyrins.
AB  - Antimicrobial photodynamic treatment combines the use of photosensitizers (PSs)
      and visible light to kill bacterial cells. Cationic porphyrins are PSs largely
      used against bacteria and, among them, those featuring one positive charge on
      each of the 5,10,15,20-tetraaryl substituent (tetracationic) are the most used.
      The aim of this study was to synthesize two dicationic 5,15-di(N-alkyl-4
      pyridyl)porphyrins, bearing methyl (PS 3) and benzyl (PS 4) N-alkylating groups,
      and to compare the efficiency in antibacterial photodynamic treatment, upon
      irradiation with a halogen-tungsten white lamp. The killing efficiency of the PS
      4 was constantly found higher than that of the PS 3 against both pure and mixed
      cultures of laboratory model microorganisms as well as against wild wastewater
      microflora. The two PSs are comparable as regards singlet oxygen generation, but
      show a different repartition coefficient; the more lipophilic benzylated PS 4
      shows a better interaction with the bacterial cells than the methylated one (PS
      3). The data support the hypothesis that an efficient PS-cell binding is required
      to obtain significant effects. A correlation among cell binding,
      photoinactivation and PS lipophilicity is suggested. 

PMID- 24041851
TI  - Role of key residues of obelin in coelenterazine binding and conversion into 2
      hydroperoxy adduct.
AB  - Bioluminescence of a variety of marine organisms is caused by monomeric Ca(2+)
      regulated photoproteins, to which a peroxy-substituted coelenterazine, 2
      hydroperoxycoelenterazine, is firmly bound. From the spatial structure the side
      chains of Tyr138, His175, Trp179, and Tyr190 of obelin are situated within the
      substrate-binding pocket at hydrogen bond distances with different atoms of the 2
      hydroperoxycoelenterazine. Here we characterized several obelin mutants with
      substitutions of these residues regarding their bioluminescence, coelenterazine
      binding, and kinetics of active obelin formation. We demonstrate that Tyr138,
      His175, Trp179, and Tyr190 are all important for coelenterazine activation;
      substitution of any of these residues leads to significant decrease of the
      apparent reaction rate. The hydrogen bond network formed by Tyr138, Trp179 and
      Tyr190 participates in the proper positioning of coelenterazine in the active
      site and subsequent stabilization of the 2-hydroperoxy adduct of coelenterazine.
      His175 might serve as a proton shuttle during 2-hydroperoxycoelenterazine
      formation. 

PMID- 24041852
TI  - Enhancement of growth, photosynthetic performance and yield by exclusion of
      ambient UV components in C3 and C4 plants.
AB  - A field experiment was conducted under tropical climate for assessing the effect
      of ambient UV-B and UV-A by exclusion of UV components on the growth,
      photosynthetic performance and yield of C3 (cotton, wheat) and C4 (amaranthus,
      sorghum) plants. The plants were grown in specially designed UV exclusion
      chambers, wrapped with filters that excluded UV-B (<315nm), UV-A+B (<400nm),
      transmitted all the UV (280-400nm) or without filters. All the four plant species
      responded to UV exclusion by a significant increase in plant height, leaf area,
      leaf biomass, total biomass accumulation and yield. Measurements of the
      chlorophyll, chlorophyll fluorescence parameters, gas exchange parameters and the
      activity of Ribulose-1,5-bisphosphate carboxylase (Rubisco) by fixation of
      (14)CO2 indicated a direct relationship between enhanced rate of photosynthesis
      and yield of the plants. Quantum yield of electron transport was enhanced by the
      exclusion of UV indicating better utilization of PAR assimilation and enhancement
      in reducing power in all the four plant species. Exclusion of UV-B in particular
      significantly enhanced the net photosynthetic rate, stomatal conductance and
      activity of Rubisco. Additional fixation of carbon due to exclusion of ambient UV
      B was channeled towards yield as there was a decrease in the level of UV-B
      absorbing substances and an increase in soluble proteins in all the four plant
      species. The magnitude of the promotion in all the parameters studied was higher
      in dicots (cotton, amaranthus) compared to monocots (wheat, sorghum) after UV
      exclusion. The results indicated a suppressive action of ambient UV-B on growth
      and photosynthesis; dicots were more sensitive than monocots in this suppression
      while no great difference in sensitivity was found between C3 and C4 plants.
      Experiments indicated the suppressive action of ambient UV on carbon fixation and
      yield of C3 and C4 plants. Exclusion of solar UV-B will have agricultural
      benefits in both C3 and C4 plants under tropical climate. 

PMID- 24041853
TI  - Efficacy of topical formulations containing Pimenta pseudocaryophyllus extract
      against UVB-induced oxidative stress and inflammation in hairless mice.
AB  - Plants rich in antioxidant substances may be a promising strategy for preventing
      UV-induced oxidative and inflammatory damage of the skin. Pimenta
      pseudocaryophyllus is native to Brazil and presents flavonoids and other
      polyphenolic compounds in high concentration. Thus, the present study evaluated
      the possible effects of topical formulations containing P. pseudocaryophyllus
      ethanolic extract (PPE) at inhibiting UV-B irradiation-induced oxidative stress
      and inflammation. PPE was administered on the dorsal skin of hairless mice using
      two formulations: F1 (non-ionic emulsion with high lipid content) and F2 (anionic
      emulsion with low lipid content) before and after UV-B irradiation. The following
      parameters were evaluated in skin samples: edema, myeloperoxidase activity,
      cytokines levels, matrix metalloprotease-9 (MMP-9) secretion/activity, reduced
      glutathione (GSH), superoxide anion and lipid peroxidation levels, and mRNA
      expression for glutathione reductase and gp91phox. The UV-B irradiation increased
      all parameters, except for IL-10 levels and glutathione reductase mRNA
      expression, which were not altered, and GSH levels, which were reduced by
      exposure to UV-B light. Treatments with F1 and F2 containing PPE inhibited UV-B
      induced edema formation (89% and 86%), myeloperoxidase activity (85% and 81%), IL
      1beta production (62% and 82%), MMP-9 activity (71% and 74%), GSH depletion (73%
      and 85%), superoxide anion (83% and 66%) and TBARS (100% and 100%) levels,
      increased glutathione reductase (2.54 and 2.55-fold) and reduced gp91phox (67%
      and 100%) mRNA expression, respectively. F2 containing PPE also increased IL-10
      levels. Therefore, this study demonstrates the effectiveness of topical
      formulations containing PPE in inhibiting UV-B irradiation-induced inflammation
      and oxidative stress of the skin. 

PMID- 24041854
TI  - Allocation of inner cells to epiblast vs primitive endoderm in the mouse embryo
      is biased but not determined by the round of asymmetric divisions (8->16- and 16
      >32-cells).
AB  - The epiblast (EPI) and the primitive endoderm (PE), which constitute foundations
      for the future embryo body and yolk sac, build respectively deep and surface
      layers of the inner cell mass (ICM) of the blastocyst. Before reaching their
      target localization within the ICM, the PE and EPI precursor cells, which display
      distinct lineage-specific markers, are intermingled randomly. Since the ICM cells
      are produced in two successive rounds of asymmetric divisions at the 8->16
      (primary inner cells) and 16->32 cell stage (secondary inner cells) it has been
      suggested that the fate of inner cells (decision to become EPI or PE) may depend
      on the time of their origin. Our method of dual labeling of embryos allowed us to
      distinguish between primary and secondary inner cells contributing ultimately to
      ICM. Our results show that the presence of two generations of inner cells in the
      32-cell stage embryo is the source of heterogeneity within the ICM. We found some
      bias concerning the level of Fgf4 and Fgfr2 expression between primary and
      secondary inner cells, resulting from the distinct number of cells expressing
      these genes. Analysis of experimental aggregates constructed using different
      ratios of inner cells surrounded by outer cells revealed that the fate of cells
      does not depend exclusively on the timing of their generation, but also on the
      number of cells generated in each wave of asymmetric division. Taking together,
      the observed regulatory mechanism adjusting the proportion of outer to inner
      cells within the embryo may be mediated by FGF signaling. 

PMID- 24041855
TI  - Preparation of resveratrol-enriched grape juice from ultrasonication treated
      grape fruits.
AB  - Grape (Vitis spp.) is a major source of resveratrol that can be eaten directly or
      after making jam, jelly, wine and juice. Resveratrol (3,5,4'-trihydroxystilbene)
      has a profound positive influence on human health, including anti-carcinogenic,
      anti-cancer, anti-inflammatory, and anti-ageing effects and the ability to lower
      blood sugar. During industrial production of grape juice, resveratrol is lost
      because of the use of clarifying agents and filtration; therefore, commercial
      grape juice contains very low amounts of resveratrol. In this study, we
      investigated the accumulation of resveratrol in grape juice prepared from three
      varieties of grape, viz. Campbell Early, Muscat Bailey A (MBA) and Kyoho,
      following post-harvest ultrasonication cleaning for 5 min and 6h of incubation in
      the dark at 25  degrees C. This process resulted in the amounts of resveratrol
      increasing by 1.53, 1.15 and 1.24 times in juice prepared from Campbell Early,
      MBA and Kyoho, respectively, without changing the amounts of total soluble
      solids. Overall, our results indicate that ultrasonication treatment of post
      harvested grape fruits can be an effective method for producing resveratrol
      enriched grape juice as well as cleaning grapes thoroughly.

PMID- 24041856
TI  - The effect of Soranus of Ephesus (98-138) on the work of midwives.
AB  - BACKGROUND: In the Roman period, midwives continued to play an important role in
      female health care primarily in the attendance of women birth. In the second
      century AD, midwives' education received a significant boost thanks to the
      distinguished physician Soranus of Ephesus. AIM: To reveal the work and important
      contribution of Soranus of Ephesus in the practice of midwifery. METHODS: The
      main bibliographic sources concerning Soranus' work on midwifery have been
      investigated and analysed. FINDINGS: In his work, Soranus described the main
      characteristics and skills of a midwife. In the practice of obstetrics, he
      performed the manoeuvre which was later called "turning the foot" and introduced
      the birth chair. His contribution in neonatology is also of a great importance as
      he provided the earliest newborn assessment. CONCLUSION: Soranus' work
      contributed in the education of midwives and influenced the practice of
      obstetrics till the Middle Ages.

PMID- 24041857
TI  - Mechanistic understanding of the modes of action of foam control agents.
AB  - In this paper we present briefly our current understanding of the modes of action
      of foam control agents (often termed "defoamers" or "antifoams"). After
      summarizing the background knowledge, reviewed in previous articles, the focus of
      the presentation is shifted to the antifoam studies from the last decade. The new
      experimental results, obtained by various research groups, are reviewed briefly
      to reveal the main mechanisms of antifoam action and the related key factors,
      governing the efficiency of the foam control agents. The role of the entry,
      spreading and bridging coefficients, of the entry barrier of the antifoam
      entities, and of the dynamics of surfactant adsorption is specifically discussed.

PMID- 24041858
TI  - Double-blind placebo-controlled randomized clinical trial on the efficacy of
      Aerosal in the treatment of sub-obstructive adenotonsillar hypertrophy and
      related diseases.
AB  - BACKGROUND: Adenotonsillar hypertrophy (ATH) is a frequent cause of upper airways
      obstructive syndromes associated to middle ear and paranasal sinuses disorders,
      swallowing and voice disorders, sleep quality disorders, and occasionally facial
      dysmorphisms. ATH treatment is essentially based on a number of medical-surgical
      aids including nasal irrigation with topical antibiotics and corticosteroids
      and/or treatment with systemic corticosteroids, immunoregulators, thermal
      treatments, adenotonsillectomy, etc. OBJECTIVES: The aim of the present study is
      to assess the efficacy of Aerosal halotherapy in the treatment of sub-obstructive
      adenotonsillar disease and correlated conditions compared to placebo treatment.
      METHODS: A total of 45 patients with sub-obstructive adenotonsillar hypertrophy
      were randomized to receive either Aerosal halotherapy or placebo for 10 treatment
      sessions. The main outcome was a reduction greater than or equal to 25% from the
      baseline of the degree of adenoid and/or tonsillar hypertrophy. RESULTS: In the
      intention-to-treat analysis, a reduction of the degree of adenoid and/or
      tonsillar hypertrophy >=25% from baseline after 10 therapy sessions was found in
      44.4% of the patients in the halotherapy arm and in 22.2% of the patients in the
      placebo arm (P=0.204). Among the secondary outcomes, the reduction of hearing
      loss after 10 treatment sessions in the halotherapy arm was higher than the
      placebo arm (P=0.018) as well as the time-dependent analysis showed significantly
      improved peak pressure in the Aerosal group (P=0.038). No side effects were
      reported during the trial. In addition, the therapy was well accepted by the
      young patients who considered it as a time for play rather than a therapy.
      CONCLUSIONS: Aerosal halotherapy can be considered a viable adjunct, albeit not a
      replacement, to conventional medical treatment of sub-obstructive adenotonsillar
      syndrome and related conditions. Further research is however needed to improve
      ATH treatment.

PMID- 24041859
TI  - The effect of the training given to the child development students about foreign
      body aspiration upon their knowledge levels.
AB  - OBJECTIVE: This study was semi-experimentally conducted in order to determine
      knowledge levels of child development students about foreign body aspiration and
      to explore the effect of the training given to these students about foreign body
      aspiration upon their knowledge levels. METHODS: The research was conducted with
      a total of 231 students who studied at the department of child development of two
      high schools and one vocational higher school in Erzincan Province located in the
      east of Turkiye between May 2011 and February 2012. The data were gathered using
      a questionnaire form of 38 questions. The training on foreign body aspiration
      (Power point presentation, video presentation and practice on a dummy) was
      provided in three phases. For the data evaluation; percentages, chi-square test
      and Mc Nemar test were used. RESULTS: It was found out in the study that 91.8% of
      the students did not take any training/course about foreign body aspiration and
      55% confronted situations of foreign body aspirations (ear, nose, airway). After
      the training about foreign body aspiration; it was noted that the number of the
      students who knew risky behaviors for foreign body aspiration increased and the
      increase in the number of the students was at the highest level among high
      schools (p<0.05). It was seen that the training was most effective among the
      university students in terms of knowing first-aid intervention in case a foreign
      body would obstruct airway among the children aged<1 year (p<0.05). CONCLUSION:
      It was noted that the training which was applied on the dummy by using visual
      aids about foreign body aspiration increased the knowledge level of the students.
      Based on this finding, it may be recommended that nurses should perform their
      counseling and educator roles more actively for the families and those who are
      responsible for the baby care about foreign body aspiration by playing a more
      active role in the health care team.

PMID- 24041860
TI  - The comparison of preincisional peritonsillar infiltration of ketamine and
      tramadol for postoperative pain relief on children following adenotonsillectomy.
AB  - OBJECTIVE: To investigate and compare the effectiveness of preincisional
      peritonsillar infiltration of ketamine and tramadol for post-operative pain on
      children following adenotonsillectomy. STUDY DESIGN: Prospective randomized
      double blind controlled study. METHODS: Seventy-five children aged 3-10 years
      undergoing adenotonsillectomy were included in study. Patients received
      injections in peritonsillar fossa of tramadol (2 mg/kg-2 ml), ketamine (0.5 mg/kg
      2 ml) or 2 ml serum physiologic. During operation heart rate, oxygen saturation,
      average mean blood pressures were recorded in every 5 min. Operation, anesthesia
      and the time that Alderete scores 9-10, patient satisfaction, analgesic
      requirements were recorded. Postoperatively nausea, vomiting, sedation,
      dysphagia, bleeding scores were recorded at 0, 10, 30, 60 min and 2, 4, 8, 12,
      18, 24h postoperatively. Pain was evaluated using modified Children's Hospital of
      Eastern Ontario Pain Scale (mCHEOPS) at fixed intervals after the procedure (15
      min and 1, 4, 12, 16, and 24h postoperatively). RESULTS: The recordings of heart
      rate, mean arterial pressure, nausea, vomiting, sedation and bleeding scores were
      similar in all groups (p>0.05). The mCHEOPS scores at 10 min, 30 min, 1h, 8h were
      significantly lower in both tramadol and ketamine group when compared with
      control (p<0.05). Use of additional analgesia at 10 min and 18 h were higher in
      control group than ketamine, tramadol group (p<0.05). Dysphagia scores were
      significantly lower for both ketamine and tramadol group when compared with
      control group (p<0.05). mCHEOPS, additional analgesia, dysphagia, patient
      satisfaction scores were similar in tramadol, ketamine groups (p>0.05).
      CONCLUSIONS: Preincisional injection of ketamine and tramadol prior to
      tonsillectomy is safe, effective method and equivalent for post-tonsillectomy
      pain, patient satisfaction, postoperative nausea, vomiting, dysphagia.

PMID- 24041862
TI  - What we don't know may hurt us: urinary drainage system tubing coils and CA-UTIs
      A prospective quality study.
AB  - Catheter-associated urinary tract infections account for >30% of infections in
      acute care hospitals. We hypothesized that coiling of/kinks in the indwelling
      urinary bladder catheter (IUBC) drainage bag tubing would increase the occurrence
      of infection/bacteriuria. Ninety-one patient events were evaluated over 60 days.
      All outcome variables trended with greater frequency among those with a coil in
      the IUBC tubing; only fever (temperature > 38.1 degrees C) correlated
      significantly between groups (P = .003). If IUBC is unavoidable, strategies such
      as keeping collection bag below the level of bladder and avoiding any coiling in
      the drainage system should be employed. Further study of these phenomena is
      needed.

PMID- 24041861
TI  - Complementary and alternative medicine therapies for perinatal depression.
AB  - Complementary and alternative medicine therapies are increasingly sought out by
      people with psychiatric disorders. In this chapter, we review the evidence for
      several commonly used CAM therapies (i.e. omega-3 fatty acids, folate, S-adenosyl
      methionine, St John's Wort, bright light therapy, exercise, massage, and
      acupuncture) in the treatment of perinatal depression. A number of these
      treatments may be reasonable to consider for women during pregnancy or
      postpartum, but the safety and efficacy of these relative to standard treatments
      must still be systematically determined. Evidence-based use of complementary and
      alternative medicine therapies treatments for perinatal depression is discussed.
      Adequately powered systematic studies are necessary to determine the role of
      complementary and alternative medicine therapies in the treatment of perinatal
      depression. 

PMID- 24041863
TI  - Efficacy of an infection control program in reducing ventilator-associated
      pneumonia in a Chinese neonatal intensive care unit.
AB  - BACKGROUND: Measures employed in preventing ventilator-associated pneumonia (VAP)
      in developing countries are rarely reported. This study evaluates the efficacy of
      an infection control program in reducing VAP in a neonatal intensive care unit
      (NICU) in China. METHODS: All neonates who received mechanical ventilation for at
      least 48 hours and were hospitalized in the NICU for >=5 days during 3 epochs
      were included. The hospital relocated to a new site during phase 2 and a bundle
      of comprehensive preventive measures against VAP were gradually implemented using
      the evidence-based practice for improving quality method. Research physicians
      recorded associated information of patients diagnosed with VAP. RESULTS: Of 491
      patients receiving mechanical ventilation, 92 (18.7%) developed VAP corresponding
      to 27.33 per 1,000 ventilator-days. The rate decreased from 48.84 per 1,000
      ventilator-days in phase 1 to 25.73 per 1,000 ventilator-days in phase 2 and
      further diminished to 18.50 per 1,000 ventilator-days in phase 3 (P < .001).
      Overall mortality rate of admitted neonates significantly decreased from 14.0% in
      phase 1 to 2.9% in phase 2 and 2.7% in phase 3 (P = .000). Gram-negative bacteria
      (95.5%) were the predominant organisms in VAP and Acinetobacter baumannii (65.2%)
      was the most frequently isolated microorganism. CONCLUSIONS: Implementing a
      multifaceted infection control program resulted in a significant reduction in VAP
      rate with long-term effects. Such interventions could be extended to other low
      income countries.

PMID- 24041864
TI  - Management of disorders of the rotator cuff: proceedings of the ISAKOS upper
      extremity committee consensus meeting.
AB  - The goal of this article is to consolidate the International Society of
      Arthroscopy, Knee Surgery & Orthopaedic Sports Medicine (ISAKOS) Upper Extremity
      Committee's (UEC's) current knowledge on rotator cuff disease and management, as
      well as highlight key unresolved issues. The rotator cuff is an anatomically
      complex structure important for providing glenohumeral function and stability as
      part of a closed chain system. Current consensus suggests rotator cuff injuries
      are most accurately diagnosed, at levels similar to diagnosis by magnetic
      resonance imaging, with a combination of cuff- and impingement-specific clinical
      tests. Updates in the understanding of acromion morphology, the insertional
      anatomy of the rotator cuff, and the role of suprascapular nerve release may
      require changes to current classification systems and surgical strategies.
      Although initial management focuses on nonoperative protocols, discussion
      continues on whether surgery for isolated impingement is clinically more
      beneficial than rehabilitation. However, clear indications have yet to be
      established for the use of single- versus double-row repair because evidence
      confirms neither is clinically efficacious than the other. Biceps tenodesis,
      however, in non-isolated cuff tears has proven more successful in addressing the
      etiology of shoulder pain and yields improved outcomes over tenotomy. Data
      reviewing the benefits of tendon transfers, shoulder prostheses, and mechanical
      scaffolds, as well as new research on the potential benefit of platelet-rich
      plasma, pluripotential stem cells, and gene therapies, will also be presented. 

PMID- 24041865
TI  - Preclinical evaluation of the mTOR-PI3K inhibitor BEZ235 in nasopharyngeal cancer
      models.
AB  - The dual PI3K-mTOR inhibitor BEZ235 was evaluated in preclinical models of
      nasopharyngeal carcinoma (NPC). The IC50 value of BEZ235 for growth was in the
      nanomolar range in vitro, induce G1 cycle arrest and apoptosis, and inhibited AKT
      and mTOR signaling in most NPC cell lines. No synergistic effect was observed
      when BEZ235 was combined with chemotherapy. BEZ235 increased MAPK activation in
      vitro but not in vivo. A daily schedule was more effective than a weekly schedule
      on tumor growth and inhibition of downstream mTOR signaling in vivo. The activity
      of BEZ235 maybe independent of the PIK3CA amplification and mutation status.

PMID- 24041867
TI  - A serum nuclear magnetic resonance-based metabolomic signature of advanced
      metastatic human breast cancer.
AB  - Breast cancer (BC) displays a high heterogeneity from histology to prognosis,
      metastatic evolution and treatment responses. We report here a (1)H NMR-based
      metabolic phenotyping study aiming at identifying coordinated metabolic serum
      changes associated with advanced metastatic breast cancer (MBC) in comparison to
      the localized early disease (EBC). A model discriminating EBC and MBC patients is
      obtained (n=85: 46 EBC and 39 MBC), and validated with an independent cohort
      (n=112: 61 EBC and 51 MBC; 89.8% sensitivity, 79.3% specificity). We identify 9
      statistically significant metabolites involved in this discrimination: histidine,
      acetoacetate, glycerol, pyruvate, glycoproteins (N-acetyl), mannose, glutamate
      and phenylalanine. This work illustrates the strong potential of NMR metabolic
      phenotyping for the diagnosis, prognosis, and management of cancer patients.

PMID- 24041869
TI  - Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini
      review.
AB  - Cytomegalovirus (CMV) infection remains a significant complication after
      hematopoietic stem cell transplantation (HSCT) and may have a deleterious impact
      on the overall outcome after transplantation. In addition to the direct effects
      of CMV infection, tissue-invasive CMV diseases may be associated with increased
      risk of graft versus host disease, myelosuppression, and invasive bacterial and
      fungal infections. Because of these direct and indirect adverse effects,
      prevention of CMV infection, mostly through pre-emptive therapy, is one of the
      essential strategies that may improve outcomes of HSCT recipients. Management of
      CMV infection relies mainly on intravenous (IV) antiviral therapy with
      ganciclovir and foscarnet, with or without IV polyclonal immunoglobulins.
      Although viral resistance remains rare, better tolerated antiviral agents with
      less serious side effects are needed, and a few will be evaluated in phase III
      clinical trials in the near future. 

PMID- 24041866
TI  - Oxidative DNA damage caused by inflammation may link to stress-induced non
      targeted effects.
AB  - A spectrum of radiation-induced non-targeted effects has been reported during the
      last two decades since Nagasawa and Little first described a phenomenon in
      cultured cells that was later called the "bystander effect". These non-targeted
      effects include radiotherapy-related abscopal effects, where changes in organs or
      tissues occur distant from the irradiated region. The spectrum of non-targeted
      effects continue to broaden over time and now embrace many types of exogenous and
      endogenous stressors that induce a systemic genotoxic response including a widely
      studied tumor microenvironment. Here we discuss processes and factors leading to
      DNA damage induction in non-targeted cells and tissues and highlight similarities
      in the regulation of systemic effects caused by different stressors. 

PMID- 24041870
TI  - Non-targeted effects induced by ionizing radiation: mechanisms and potential
      impact on radiation induced health effects.
AB  - Not-targeted effects represent a paradigm shift from the "DNA centric" view that
      ionizing radiation only elicits biological effects and subsequent health
      consequences as a result of an energy deposition event in the cell nucleus. While
      this is likely true at higher radiation doses (>1 Gy), at low doses (<100 mGy)
      non-targeted effects associated with radiation exposure might play a significant
      role. Here definitions of non-targeted effects are presented, the potential
      mechanisms for the communication of signals and signaling networks from
      irradiated cells/tissues are proposed, and the various effects of this intra- and
      intercellular signaling are described. We conclude with speculation on how these
      observations might lead to and impact long-term human health outcomes.

PMID- 24041868
TI  - Non-small cell lung cancer is susceptible to induction of DNA damage responses
      and inhibition of angiogenesis by telomere overhang oligonucleotides.
AB  - Exposure of the telomere overhang acts as a DNA damage signal, and exogenous
      administration of an 11-base oligonucleotide homologous to the 3'-telomere
      overhang sequence (T-oligo) mimics the effects of overhang exposure by inducing
      senescence and cell death in non-small cell lung cancer (NSCLC) cells, but not in
      normal bronchial epithelial cells. T-oligo-induced decrease in cellular
      proliferation in NSCLC is likely directed through both p53 and its homolog, p73,
      with subsequent induction of senescence and expression of senescence-associated
      proteins, p21, p33(ING), and p27(Kip1) both in vivo and in vitro. Additionally, T
      oligo decreases tumor size and inhibits angiogenesis through decreased VEGF
      signaling and increased TSP-1 expression.

PMID- 24041871
TI  - Words and possible words in early language acquisition.
AB  - In order to acquire language, infants must extract its building blocks-words-and
      master the rules governing their legal combinations from speech. These two
      problems are not independent, however: words also have internal structure. Thus,
      infants must extract two kinds of information from the same speech input. They
      must find the actual words of their language. Furthermore, they must identify its
      possible words, that is, the sequences of sounds that, being morphologically well
      formed, could be words. Here, we show that infants' sensitivity to possible words
      appears to be more primitive and fundamental than their ability to find actual
      words. We expose 12- and 18-month-old infants to an artificial language
      containing a conflict between statistically coherent and structurally coherent
      items. We show that 18-month-olds can extract possible words when the
      familiarization stream contains marks of segmentation, but cannot do so when the
      stream is continuous. Yet, they can find actual words from a continuous stream by
      computing statistical relationships among syllables. By contrast, 12-month-olds
      can find possible words when familiarized with a segmented stream, but seem
      unable to extract statistically coherent items from a continuous stream that
      contains minimal conflicts between statistical and structural information. These
      results suggest that sensitivity to word structure is in place earlier than the
      ability to analyze distributional information. The ability to compute nontrivial
      statistical relationships becomes fully effective relatively late in development,
      when infants have already acquired a considerable amount of linguistic knowledge.
      Thus, mechanisms for structure extraction that do not rely on extensive sampling
      of the input are likely to have a much larger role in language acquisition than
      general-purpose statistical abilities. 

PMID- 24041872
TI  - Blockface histology with optical coherence tomography: a comparison with Nissl
      staining.
AB  - Spectral domain optical coherence tomography (SD-OCT) is a high resolution
      imaging technique that generates excellent contrast based on intrinsic optical
      properties of the tissue, such as neurons and fibers. The SD-OCT data acquisition
      is performed directly on the tissue block, diminishing the need for cutting,
      mounting and staining. We utilized SD-OCT to visualize the laminar structure of
      the isocortex and compared cortical cytoarchitecture with the gold standard Nissl
      staining, both qualitatively and quantitatively. In histological processing,
      distortions routinely affect registration to the blockface image and prevent
      accurate 3D reconstruction of regions of tissue. We compared blockface
      registration to SD-OCT and Nissl, respectively, and found that SD-OCT-blockface
      registration was significantly more accurate than Nissl-blockface registration.
      Two independent observers manually labeled cortical laminae (e.g. III, IV and V)
      in SD-OCT images and Nissl stained sections. Our results show that OCT images
      exhibit sufficient contrast in the cortex to reliably differentiate the cortical
      layers. Furthermore, the modalities were compared with regard to cortical laminar
      organization and showed good agreement. Taken together, these SD-OCT results
      suggest that SD-OCT contains information comparable to standard histological
      stains such as Nissl in terms of distinguishing cortical layers and architectonic
      areas. Given these data, we propose that SD-OCT can be used to reliably generate
      3D reconstructions of multiple cubic centimeters of cortex that can be used to
      accurately and semi-automatically perform standard histological analyses. 

PMID- 24041873
TI  - Spatial-temporal modelling of fMRI data through spatially regularized mixture of
      hidden process models.
AB  - Previous work investigated a range of spatio-temporal constraints for fMRI data
      analysis to provide robust detection of neural activation. We present a mixture
      based method for the spatio-temporal modelling of fMRI data. This approach
      assumes that fMRI time series are generated by a probabilistic superposition of a
      small set of spatio-temporal prototypes (mixture components). Each prototype
      comprises a temporal model that explains fMRI signals on a single voxel and the
      model's "region of influence" through a spatial prior over the voxel space. As
      the key ingredient of our temporal model, the Hidden Process Model (HPM)
      framework proposed in Hutchinson et al. (2009) is adopted to infer the
      overlapping cognitive processes triggered by stimuli. Unlike the original HPM
      framework, we use a parametric model of Haemodynamic Response Function (HRF) so
      that biological constraints are naturally incorporated in the HRF estimation. The
      spatial priors are defined in terms of a parameterised distribution. Thus, the
      total number of parameters in the model does not depend on the number of voxels.
      The resulting model provides a conceptually principled and computationally
      efficient approach to identify spatio-temporal patterns of neural activation from
      fMRI data, in contrast to most conventional approaches in the literature focusing
      on the detection of spatial patterns. We first verify the proposed model in a
      controlled experimental setting using synthetic data. The model is further
      validated on real fMRI data obtained from a rapid event-related visual
      recognition experiment (Mayhew et al., 2012). Our model enables us to evaluate in
      a principled manner the variability of neural activations within individual
      regions of interest (ROIs). The results strongly suggest that, compared with
      occipitotemporal regions, the frontal ones are less homogeneous, requiring two
      HPM prototypes per region. Despite the rapid event-related experimental design,
      the model is capable of disentangling the perceptual judgement and motor response
      processes that are both activated in the frontal ROIs. Spatio-temporal
      heterogeneity in the frontal regions seems to be associated with diverse dynamic
      localizations of the two hidden processes in different subregions of frontal
      ROIs. 

PMID- 24041874
TI  - Algorithmic procedures for Bayesian MEG/EEG source reconstruction in SPM.
AB  - The MEG/EEG inverse problem is ill-posed, giving different source reconstructions
      depending on the initial assumption sets. Parametric Empirical Bayes allows one
      to implement most popular MEG/EEG inversion schemes (Minimum Norm, LORETA, etc.)
      within the same generic Bayesian framework. It also provides a cost-function in
      terms of the variational Free energy-an approximation to the marginal likelihood
      or evidence of the solution. In this manuscript, we revisit the algorithm for
      MEG/EEG source reconstruction with a view to providing a didactic and practical
      guide. The aim is to promote and help standardise the development and
      consolidation of other schemes within the same framework. We describe the
      implementation in the Statistical Parametric Mapping (SPM) software package,
      carefully explaining each of its stages with the help of a simple simulated data
      example. We focus on the Multiple Sparse Priors (MSP) model, which we compare
      with the well-known Minimum Norm and LORETA models, using the negative
      variational Free energy for model comparison. The manuscript is accompanied by
      Matlab scripts to allow the reader to test and explore the underlying algorithm. 

PMID- 24041875
TI  - Treatment and prognostic factors in pleuropulmonary blastoma: an EXPeRT report.
AB  - BACKGROUND: Pleuropulmonary blastoma (PPB) is an aggressive embryonal malignancy
      presenting in early childhood, presumably arising from pleuropulmonary
      mesenchyme. The European Cooperative Study Group for Paediatric Rare Tumours
      (EXPeRT) analysed its data on this tumour. METHODS: This analysis concerns
      patients aged 0-17years with histologically-confirmed PPB registered up to 2008
      in national databases in Italy, France and the United Kingdom and Poland. Lesions
      were classified as type I, II or III according to Dehner's classification.
      FINDINGS: Sixty-five patients were considered (13 type I, 24 type II and 28 type
      III). Most tumours were large (91% >5cm) and invaded the parietal pleura (29),
      mediastinum (10), major vessels (four) or pericardium (three). Regional nodes
      were involved in two cases, and three had metastases. The median follow-up was
      5years (0.6-22). For type I patients, 5-year progression free survival (PFS) was
      83.3% and overall survival 91.7%; six patients received no further treatment
      after surgery, but two relapsed. All type II/III PPB had chemotherapy (CT) and
      their 5-year PFS was 42.9% (27.7-57.2). On univariate analysis, favourable
      prognostic factors were: complete tumour resection at diagnosis (p=0.008); and
      absence of invasiveness (p=0.02); for type II/III tumours, type of CT was also a
      significant factor (patients given doxorubicin fared better, with a 5-year PFS of
      70% versus 31.3% [p=0.01]). INTERPRETATIONS: Type I PPB patients' outcome was
      satisfactory. Complete resection at diagnosis seems important but rarely feasible
      for type II/III tumours, who benefited from doxorubicin-containing CT regimens.
      These results will inform the EXPeRT group's PPB treatment guidelines.

PMID- 24041876
TI  - Variation in detection of ductal carcinoma in situ during screening mammography:
      a survey within the International Cancer Screening Network.
AB  - BACKGROUND: There is concern about detection of ductal carcinoma in situ (DCIS)
      in screening mammography. DCIS accounts for a substantial proportion of screen
      detected lesions but its effect on breast cancer mortality is debated. The
      International Cancer Screening Network conducted a comparative analysis to
      determine variation in DCIS detection. PATIENTS AND METHODS: Data were collected
      during 2004-2008 on number of screening examinations, detected breast cancers,
      DCIS cases and Globocan 2008 breast cancer incidence rates derived from national
      or regional cancer registers. We calculated screen-detection rates for breast
      cancers and DCIS. RESULTS: Data were obtained from 15 screening settings in 12
      countries; 7,176,050 screening examinations; 29,605 breast cancers and 5324 DCIS
      cases. The ratio between highest and lowest breast cancer incidence was 2.88 (95%
      confidence interval (CI) 2.76-3.00); 2.97 (95% CI 2.51-3.51) for detection of
      breast cancer; and 3.49 (95% CI 2.70-4.51) for detection of DCIS. CONCLUSIONS:
      Considerable international variation was found in DCIS detection. This variation
      could not be fully explained by variation in incidence nor in breast cancer
      detection rates. It suggests the potential for wide discrepancies in management
      of DCIS resulting in overtreatment of indolent DCIS or undertreatment of
      potentially curable disease. Comprehensive cancer registration is needed to
      monitor DCIS detection. Efforts to understand discrepancies and standardise
      management may improve care.

PMID- 24041877
TI  - Management of low-risk early-stage cervical cancer: should conization, simple
      trachelectomy, or simple hysterectomy replace radical surgery as the new standard
      of care?
AB  - The standard treatment for women with early-stage cervical cancer (IA2-IB1)
      remains radical hysterectomy with pelvic lymphadenectomy. In select patients
      interested in future fertility, the option of radical trachelectomy with pelvic
      lymphadenectomy is also considered a viable option. The possibility of less
      radical surgery may be appropriate not only for patients desiring to preserve
      fertility but also for all patients with low-risk early-stage cervical cancer.
      Recently, a number of studies have explored less radical surgical options for
      early-stage cervical cancer, including simple hysterectomy, simple trachelectomy,
      and cervical conization with or without sentinel lymph node biopsy and pelvic
      lymph node dissection. Such options may be available for patients with low-risk
      early-stage cervical cancer. Criteria that define this low-risk group include:
      squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma, tumor size <2 cm,
      stromal invasion <10mm, and no lymph-vascular space invasion. In this report, we
      provide a review of the existing literature on the conservative management of
      cervical cancer and describe ongoing multi-institutional trials evaluating the
      role of conservative surgery in selected patients with early-stage cervical
      cancer.

PMID- 24041878
TI  - Referrals to phase I clinical trials in a gynecologic oncology unit.
AB  - OBJECTIVES: Previous reviews of phase I clinical trials report limited response
      rates. Development of novel biologic agents and trials designs have increased
      these rates. A contemporary appraisal of phase I clinical trials in gynecologic
      malignancies could help validate these findings. METHODS: Retrospectively
      reviewed records for 410 patients with gynecologic malignancies treated in a
      phase I unit, January 1999 to October 2012. Patient characteristics and treatment
      outcomes were abstracted and analyzed. RESULTS: Patients enrolled in 43 different
      phase I trials, 17 phase Ia, 17 phase Ib dose escalation and 9 dose expansion. 9
      trials (21%) investigated unique cytotoxic delivery methods, 15 (35%)
      conventional cytotoxic plus novel agents and 19 (44%) novel agents alone. For
      patients treated in the first-line setting, 90 (74.4%) achieved CR, 20 (16.5%)
      PR, 9 (7.4%) SD and 2 (1.7%) PD, yielding an overall response rate of 90.9%. In
      patients treated for recurrent disease, 2 (1.6%) achieved CR, 11 (8.9%) PR, 57
      (46.0%) SD and 54 (43.5%) PD, yielding a response rate of 11% and an overall
      clinical benefit rate of 57%. Response rate for molecular targeted therapies was
      11.5% with an overall clinical benefit rate of 46.2%. Patients with prior anti
      angiogenic exposure had comparable median PFS to those who had not been
      previously exposed (3.5 vs. 4.0 months, p = 0.29). CONCLUSIONS: Results support
      referral of gynecologic cancer patients for phase I clinical trials. Patients
      with advanced, heavily pretreated disease fare at least as well as they do on
      phase II trials and a proportion of them can attain an objective response or
      stabilization of their disease.

PMID- 24041879
TI  - Short term outcomes following breast cancer surgery in pregnant women.
AB  - OBJECTIVE: Breast cancer is the most common malignancy in pregnancy with an
      estimated prevalence of 1 per 3000 pregnancies. The National Comprehensive Cancer
      Network (NCCN) guidelines advocate for surgical management in all trimesters for
      pregnant women with breast cancer but few studies have examined the impact breast
      cancer surgery has on outcomes in pregnant women. We aimed to identify
      differences in short term outcomes after breast cancer surgery between age
      matched pregnant and non-pregnant women. METHODS: This was a retrospective, cross
      sectional study utilizing the Health Care Utilization Project-Nationwide Impact
      Sample (HCUP-NIS) database from 1999 to 2006. All pregnant women with breast
      cancer undergoing lumpectomy or mastectomy were compared to age-matched non
      pregnant women. Demographics, in-hospital mortality, length of stay, hospital
      cost, and discharge disposition were reviewed. Statistical analysis was performed
      with chi-square, Student's t-test, and ANOVA with p<0.05 deemed significant.
      RESULTS: Over an 8 year period, 185 pregnant women (mean age 35 years) and 47,985
      non-pregnant age-restricted women (mean age 45 years) who underwent breast cancer
      surgery were identified. There was no significant difference between in-hospital
      mortality, length of stay, cost of hospitalization, or discharge disposition in
      these women. CONCLUSION: Pregnant and non-pregnant women undergoing breast
      surgery for cancer have similar short-term outcomes.

PMID- 24041880
TI  - Venous thromboembolism during primary treatment of ovarian clear cell carcinoma
      is associated with decreased survival.
AB  - OBJECTIVES: To determine the impact of venous thromboembolism (VTE) during
      primary treatment of ovarian clear cell carcinoma (OCCC) on survival. METHODS:
      After Institutional Review Board approval, 74 cases of OCCC were retrieved from
      our pathology files. Clinical and pathological data were obtained by medical
      record and pathology review. Standard statistical analyses were performed.
      RESULTS: Among 74 patients with OCCC, VTE was diagnosed in 11 (15%) during
      primary treatment and 7 (9%) at time of cancer recurrence. 56 (76%) patients
      never developed VTE. Patients with VTE during OCCC primary treatment had shorter
      progression-free survival (PFS) and overall survival (OS) than OCCC patients
      without VTE (median PFS 11 vs. 76 months, p=0.01, median OS 19 vs. 90 months,
      p=0.001). Patients with VTE during OCCC primary treatment had a 3.9-fold increase
      in risk of recurrence (p=0.007) and a 6.3-fold increase in risk of death
      (p<0.001). After controlling for cancer stage, VTE during OCCC primary treatment
      remained an independent prognostic factor for death (HR=3.6, p=0.005). No patient
      died of VTE. CONCLUSIONS: VTE during OCCC primary treatment is associated with a
      significantly higher risk of cancer recurrence and death. This increased risk is
      not attributable to VTE-related mortality and raises the possibility that a
      paracrine circuit involving thrombosis might contribute to a more aggressive
      tumor biology.

PMID- 24041881
TI  - The clonal distribution and diversity of extraintestinal Escherichia coli
      isolates vary according to patient characteristics.
AB  - The clonal distribution of Escherichia coli across an unselected population in
      the current era of widespread antimicrobial resistance is incompletely defined.
      In this study, we used a newly described clonal typing strategy based on
      sequencing of fumC and fimH (i.e., CH typing) to infer multilocus sequence types
      (STs) for 299 consecutive, nonduplicate extraintestinal E. coli isolates from all
      cultures submitted to Olmsted County, MN, laboratories in February and March 2011
      and then compared STs with epidemiological data. Forty-seven different STs were
      identified, most commonly ST131 (27%), ST95 (11%), ST73 (8%), ST127 (6%), and
      ST69 (5%). Isolates from these five STs comprised two-thirds of health care
      associated (HA) isolates but only half of community-associated (CA) isolates.
      ST131 was represented overwhelmingly (88%) by a single recently expanded H30
      subclone, which was the most extensively antimicrobial-resistant subclone overall
      and was especially predominant in HA infections and among adults >50 years old.
      In contrast, among patients 11 to 50 years old, ST69, -95, and -73 were more
      common. Because of the preponderance of the H30 subclone of ST131, ST diversity
      was lower among HA than CA isolates, and among antimicrobial-resistant than
      antimicrobial-susceptible isolates, which otherwise had similar ST distributions.
      In conclusion, in this U.S. Midwest region, the distribution and diversity of STs
      among extraintestinal E. coli clinical isolates vary by patient age, type of
      infection, and resistance phenotype. ST131 predominates among young children and
      the elderly, HA infections, and antimicrobial-resistant isolates, whereas other
      well-known pathogenic lineages are more common among adolescents and young
      adults, CA infections, and antimicrobial-susceptible isolates. 

PMID- 24041882
TI  - An FtsZ-targeting prodrug with oral antistaphylococcal efficacy in vivo.
AB  - The bacterial cell division protein FtsZ represents a novel antibiotic target
      that has yet to be exploited clinically. The benzamide PC190723 was among the
      first FtsZ-targeting compounds to exhibit in vivo efficacy in a murine infection
      model system. Despite its initial promise, the poor formulation properties of the
      compound have limited its potential for clinical development. We describe here
      the development of an N-Mannich base derivative of PC190723 with enhanced drug
      like properties and oral in vivo efficacy. The N-Mannich base derivative (TXY436)
      is ~100-fold more soluble than PC190723 in an acidic aqueous vehicle (10 mM
      citrate, pH 2.6) suitable for oral in vivo administration. At physiological pH
      (7.4), TXY436 acts as a prodrug, converting to PC190723 with a conversion half
      life of 18.2 +/- 1.6 min. Pharmacokinetic analysis following intravenous
      administration of TXY436 into mice yielded elimination half-lives of 0.26 and
      0.96 h for the TXY436 prodrug and its PC190723 product, respectively. In
      addition, TXY436 was found to be orally bioavailable and associated with
      significant extravascular distribution. Using a mouse model of systemic infection
      with methicillin-sensitive Staphylococcus aureus or methicillin-resistant S.
      aureus, we show that TXY436 is efficacious in vivo upon oral administration. In
      contrast, the oral administration of PC190723 was not efficacious. Mammalian
      cytotoxicity studies of TXY436 using Vero cells revealed an absence of toxicity
      up to compound concentrations at least 64 times greater than those associated
      with antistaphylococcal activity. These collective properties make TXY436 a
      worthy candidate for further investigation as a clinically useful agent for the
      treatment of staphylococcal infections. 

PMID- 24041883
TI  - Antiplasmodial activity and mechanism of action of RSM-932A, a promising
      synergistic inhibitor of Plasmodium falciparum choline kinase.
AB  - We have investigated the mechanism of action of inhibition of the choline kinase
      of P. falciparum (p.f.-ChoK) by two inhibitors of the human ChoKalpha, MN58b and
      RSM-932A, which have previously been shown to be potent antitumoral agents. The
      efficacy of these inhibitors against p.f.-ChoK is investigated using enzymatic
      and in vitro assays. While MN58b may enter the choline/phosphocholine binding
      site, RSM-932A appears to have an altogether novel mechanism of inhibition and is
      synergistic with respect to both choline and ATP. A model of inhibition for RSM
      932A in which this inhibitor traps p.f.-ChoK in a phosphorylated intermediate
      state blocking phosphate transfer to choline is presented. Importantly, MN58b and
      RSM-932A have in vitro inhibitory activity in the low nanomolar range and are
      equally effective against chloroquine-sensitive and chloroquine-resistant
      strains. RSM-932A and MN58b significantly reduced parasitemia and induced the
      accumulation of trophozoites and schizonts, blocking intraerythrocytic
      development and interfering with parasite egress or invasion, suggesting a delay
      of the parasite maturation stage. The present data provide two new potent
      structures for the development of antimalarial compounds and validate p.f.-ChoK
      as an accessible drug target against the parasite. 

PMID- 24041884
TI  - Effects of body size and gender on the population pharmacokinetics of artesunate
      and its active metabolite dihydroartemisinin in pediatric malaria patients.
AB  - Despite the important role of the antimalarial artesunate and its active
      metabolite dihydroartemisinin (DHA) in malaria treatment efforts, there are
      limited data on the pharmacokinetics of these agents in pediatric patients. This
      study evaluated the effects of body size and gender on the pharmacokinetics of
      artesunate-DHA using data from pediatric and adult malaria patients. Nonlinear
      mixed-effects modeling was used to obtain a base model consisting of first-order
      artesunate absorption and one-compartment models for artesunate and for DHA.
      Various methods of incorporating effects of body size descriptors on clearance
      and volume parameters were tested. An allometric scaling model for weight and a
      linear body surface area (BSA) model were deemed optimal. The apparent clearance
      and volume of distribution of DHA obtained with the allometric scaling model,
      normalized to a 38-kg patient, were 63.5 liters/h and 65.1 liters, respectively.
      Estimates for the linear BSA model were similar. The 95% confidence intervals for
      the estimated gender effects on clearance and volume parameters for artesunate
      fell outside the predefined no-relevant-clinical-effect interval of 0.75 to 1.25.
      However, the effect of gender on apparent DHA clearance was almost entirely
      contained within this interval, suggesting a lack of an influence of gender on
      this parameter. Overall, the pharmacokinetics of artesunate and DHA following
      oral artesunate administration can be described for pediatric patients using
      either an allometric scaling or linear BSA model. Both models predict that, for a
      given artesunate dose in mg/kg of body weight, younger children are expected to
      have lower DHA exposure than older children or adults. 

PMID- 24041885
TI  - Mechanism of action of the novel aminomethylcycline antibiotic omadacycline.
AB  - Omadacycline is a novel first-in-class aminomethylcycline with potent activity
      against important skin and pneumonia pathogens, including community-acquired
      methicillin-resistant Staphylococcus aureus (MRSA), beta-hemolytic streptococci,
      penicillin-resistant Streptococcus pneumoniae, Haemophilus influenzae, and
      Legionella. In this work, the mechanism of action for omadacycline was further
      elucidated using a variety of models. Functional assays demonstrated that
      omadacycline is active against strains expressing the two main forms of
      tetracycline resistance (efflux and ribosomal protection). Macromolecular
      synthesis experiments confirmed that the primary effect of omadacycline is on
      bacterial protein synthesis, inhibiting protein synthesis with a potency greater
      than that of tetracycline. Biophysical studies with isolated ribosomes confirmed
      that the binding site for omadacycline is similar to that for tetracycline. In
      addition, unlike tetracycline, omadacycline is active in vitro in the presence of
      the ribosomal protection protein Tet(O). 

PMID- 24041886
TI  - Thioridazine pharmacokinetic-pharmacodynamic parameters "Wobble" during treatment
      of tuberculosis: a theoretical basis for shorter-duration curative monotherapy
      with congeners.
AB  - Phenothiazines are being repurposed for treatment of tuberculosis. We examined
      time-kill curves of thioridazine and first-line drugs against log-growth-phase
      and semidormant bacilli under acidic conditions and nonreplicating persistent
      Mycobacterium tuberculosis. While both the potency and the efficacy of first-line
      drugs declined dramatically as M. tuberculosis replication rates decreased, those
      of thioridazine improved. The mutation prevalence to 3 times the thioridazine MIC
      was <1 * 10(-11), better than for >=2 first-line drugs combined. Hollow fiber
      system studies revealed that the relationship between sterilizing effect and
      pharmacodynamic indices (PDI) was characterized by an r(2) of 0.88 for peak/MIC,
      an r(2) of 0.47 for the area under the concentration-time curve (AUC) to MIC, and
      an r(2) of 0.14 for the cumulative percentage of a 24-h period that the drug
      concentration exceeds the MIC under steady-state pharmacokinetic conditions
      (%TMIC) at the end of the first week. However, the PDI linked to effect "wobbled"
      as the duration of therapy increased, so that by the fourth week the r(2) was
      0.88 for AUC/MIC, 0.78 for %TMIC, and 0.72 for peak/MIC. This "wobble" has
      implications on general pharmacokinetic/pharmacodynamic theory, whereby efficacy
      is linked to only one of the three PDIs in deterministic models. The potency
      changed 8.9-fold from the first to the fourth weeks. The non-protein-bound
      AUC/MIC associated with maximal kill at the end of therapy was 50.53 (protein
      binding = 99.5%). This thioridazine exposure was calculated to extinguish all
      three M. tuberculosis metabolic populations in human lungs in only 42.9 days of
      monotherapy. However, this concentration exceeds the 2- to 8-mg/liter
      thioridazine concentration in serum known to be lethal to humans. Therefore, the
      way forward for phenothiazine monotherapy that also reduces therapy duration is
      via synthesis of less toxic congeners. 

PMID- 24041887
TI  - Tissue pharmacokinetics of cefazolin in patients with lower limb infections.
AB  - Cefazolin, a first-generation cephalosporin with activity against methicillin
      susceptible Staphylococcus aureus and streptococci, is often used to treat lower
      limb infections caused by these pathogens. Antimicrobial penetration is often
      limited in these patients due to compromised vasculature. Therefore, we sought to
      evaluate the exposure profile of cefazolin in serum and tissue in patients with
      lower limb infections. An in vivo microdialysis catheter was inserted into the
      tissue near the margin of the wound and constantly perfused with lactated
      Ringer's solution. Steady-state serum and tissue samples were simultaneously
      collected over a dosing interval. Serum protein binding was also assessed. Serum
      concentrations were analyzed by noncompartmental analysis. Tissue concentrations
      were corrected for percent in vivo recovery by using the retrodialysis technique.
      Seven patients with a mean weight of 95.45 +/- 18.51 kg and a mean age of 54 +/-
      19 years were enrolled. Six patients received 1 g every 8 h, and one patient
      received 2 g every 24 h due to acute kidney injury. The free area under the curve
      from 0 to 8 h (fAUC0-8) values for serum and wound were 48.0 +/- 18.66 and 56.35
      +/- 41.17 MUg . h/ml, respectively, for the patients receiving 1 g every 8 h. The
      fAUC0-24 values for serum and wound were 1,326.1 and 253.9 MUg . h/ml,
      respectively, for the single patient receiving 2 g every 24 h. The mean tissue
      penetration ratio (tissue/serum fAUC ratio) was 1.06. These data suggest that the
      amount of time that free-drug concentrations remain above the MIC (fT>MIC) for
      cefazolin in wound tissue is adequate to treat patients with lower limb
      infections. 

PMID- 24041888
TI  - Comparative evaluation of serotonin toxicity among veterans affairs patients
      receiving linezolid and vancomycin.
AB  - Despite the theoretical risk of serotonin toxicity (ST) with linezolid, "real
      world" clinical evaluations of the risk of ST in patients receiving linezolid
      have been limited to case reports and noncomparator studies. An observational,
      matched-cohort study was conducted to evaluate the risk of ST among hospitalized
      patients who received linezolid or vancomycin at the Upstate New York Veterans
      Affairs Healthcare Network (Veterans Integrated Service Network 2 [VISN-2]).
      Matching criteria included VISN-2 hospital, hospital ward, prior hospital length
      of stay, age, and baseline platelet counts. The patients' electronic medical
      records were evaluated for symptoms consistent with ST and the Hunter serotonin
      toxicity criteria (HSTC) using an intensive, natural word search algorithm. The
      study included 251 matched pairs. Demographics and comorbidities were similar
      between groups. Over half of the study population received at least one
      concurrent medication with serotonergic activity. Receipt of agents with
      serotonergic activity was more pronounced in the vancomycin group, and the higher
      frequency was due to concomitant antihistamine and antiemetic use. Antidepressant
      use, including selective serotonin reuptake inhibitors (SSRIs), was similar
      between groups. No patients in either group were found to meet the criteria using
      the word search algorithm for ST. Fewer linezolid patients than vancomycin
      patients met the HSTC overall (3.2% versus 8.8%) and when stratified by receipt
      of a concurrent serotonergic agent (4.3% versus 12.4%). Of the patients meeting
      the HSTC, most had past or present comorbidities that may have contributed to or
      overlapped the HSTC. This study of hospitalized patients revealed comparably low
      frequencies of adverse events potentially related to ST among patients who
      received linezolid or vancomycin. 

PMID- 24041889
TI  - IMP-33, a New IMP variant detected in Pseudomonas aeruginosa from Sicily.

PMID- 24041890
TI  - In vitro susceptibility of Aspergillus fumigatus to isavuconazole: correlation
      with itraconazole, voriconazole, and posaconazole.
AB  - Triazoles are first-line agents for treating aspergillosis. The prevalence of
      azole resistance in Aspergillus fumigatus is increasing, and cross-resistance is
      a growing concern. In this study, the susceptibilities of 40 A. fumigatus
      clinical isolates were tested by using the CLSI method with amphotericin B,
      itraconazole, voriconazole, posaconazole, and the new triazole isavuconazole.
      Isavuconazole MICs were higher in strains with reduced susceptibilities to other
      triazoles, mirroring changes in voriconazole susceptibility. Isavuconazole MICs
      differed depending on the Cyp51A substitution. 

PMID- 24041891
TI  - In vivo efficacy of humanized ceftaroline fosamil-avibactam exposures in a
      polymicrobial infection model.
AB  - Although Gram-positive cocci are the most common pathogens in diabetic foot
      infections, these infections often are polymicrobial. The objective of this study
      was to assess the efficacy of a simulated human dose of 600 mg ceftaroline
      fosamil-600 mg avibactam every 8 h as a 1-h infusion in a polymicrobial in vivo
      murine model. Seven isolates were used (3 methicillin-resistant Staphylococcus
      aureus [MRSA] isolates, 1 methicillin-susceptible S. aureus [MSSA] isolate, 1
      Escherichia coli isolate, 1 Enterobacter cloacae isolate, and 1 Bacteroides
      fragilis isolate) in various combinations in an immunocompromised polymicrobial
      tissue infection to assess the efficacy of the simulated regimen. Each infection
      was comprised of at least one S. aureus isolate with a MIC of 0.25 to 1 MUg/ml
      and one Enterobacteriaceae isolate with a MIC of 1 or 4 MUg/ml. Eight of 16
      infections also included B. fragilis, with a MIC of 0.5 MUg/ml, as a third
      organism. Efficacy was evaluated after 24 h as the change in log10 CFU from the
      level of 0-h controls. Efficacy was seen against all isolate combinations, with
      at least a 1-log kill against Enterobacteriaceae and a minimum of a 2-log kill
      against S. aureus and B. fragilis isolates. These bacterial reductions correlate
      with free drug concentration above the MIC (fT>MIC) produced by the humanized
      regimen of 100, 86, and 56% at MICs of 1, 2, and 4 MUg/ml, respectively. The
      humanized regimen of 600 mg ceftaroline fosamil-600 mg avibactam every 8 h as a 1
      h infusion showed predictable efficacy against all infections tested in this
      model. These data support further clinical investigation of ceftaroline fosamil
      avibactam for the treatment of polymicrobial tissue infections. 

PMID- 24041892
TI  - Optimizing empiric antibiotic therapy in patients with severe beta-lactam
      allergy.
AB  - Antibiotic selection is challenging in patients with severe beta-lactam allergy
      due to declining reliability of alternate antibiotics. Organisms isolated from
      these patients may exhibit unique resistance phenotypes. The objective of this
      study was to determine which alternate antibiotics or combinations provide
      adequate empirical therapy for patients with beta-lactam allergy who develop Gram
      negative infections at our institution. We further sought to determine the
      effects of risk factors for drug resistance on empirical adequacy. A
      retrospective analysis was conducted for adult patients hospitalized from
      September 2009 to May 2010 who had a severe beta-lactam allergy and a urine,
      blood, or respiratory culture positive for a Gram-negative organism and who met
      predefined criteria for infection. Patient characteristics, culture and
      susceptibility data, and predefined risk factors for antibiotic resistance were
      collected. Adequacies of beta-lactam and alternate antibiotics were compared for
      all infections and selected subsets. The primary outcome was adequacy of each
      alternate antibiotic or combination for all infections. One hundred sixteen
      infections (40 pneumonias, 67 urinary tract infections, and 9 bacteremias) were
      identified. Single alternate agents were adequate less frequently than beta
      lactams and combination regimens. Only in cases without risk factors for
      resistance did single-agent regimens demonstrate acceptable adequacy rates; each
      factor conferred a doubling of risk for resistance. Resistance risk factors
      should be considered in selecting empirical antibiotics for Gram-negative
      pathogens in patients unable to take beta-lactams due to severe allergy. 

PMID- 24041893
TI  - Prospective multicenter study of pathogen distributions in early-onset and late
      onset hospital-acquired pneumonia in china.

PMID- 24041894
TI  - Hollow-fiber pharmacodynamic studies and mathematical modeling to predict the
      efficacy of amoxicillin for anthrax postexposure prophylaxis in pregnant women
      and children.
AB  - Amoxicillin is considered an option for postexposure prophylaxis of Bacillus
      anthracis in pregnant and postpartum women who are breastfeeding and in children
      because of the potential toxicities of ciprofloxacin and doxycycline to the fetus
      and child. The amoxicillin regimen that effectively kills B. anthracis and
      prevents resistance is unknown. Fourteen-day dose range and dose fractionation
      studies were conducted in in vitro pharmacodynamic models to identify the
      exposure intensity and pharmacodynamic index of amoxicillin that are linked with
      optimized killing of B. anthracis and resistance prevention. Studies with
      dicloxacillin, a drug resistant to B. anthracis beta-lactamase, evaluated the
      role of beta-lactamase production in the pharmacodynamic indices for B. anthracis
      killing and resistance prevention. Dose fractionation studies showed that
      trough/MIC and not time above MIC was the index for amoxicillin that was linked
      to successful outcome through resistance prevention. Failure of amoxicillin
      regimens was due to inducible or stable high level expression of beta-lactamases.
      Studies with dicloxacillin demonstrated that a time above MIC of >=94% was linked
      with treatment success when B. anthracis beta-lactamase activity was negated.
      Recursive partitioning analysis showed that amoxicillin regimens that produced
      peak concentrations of <10.99 MUg/ml and troughs of >1.75 MUg/ml provided a 100%
      success rate. Other amoxicillin peak and trough values produced success rates of
      28 to 67%. For postpartum and pregnant women and children, Monte Carlo
      simulations predicted success rates for amoxicillin at 1 g every 8 h (q8h) of 53,
      33, and 44% (30 mg/kg q8h), respectively. We conclude that amoxicillin is
      suboptimal for postexposure prophylaxis of B. anthracis in pregnant and
      postpartum women and in children. 

PMID- 24041895
TI  - Pharmacological basis of beta-lactamase inhibitor therapeutics: tazobactam in
      combination with Ceftolozane.
AB  - We recently investigated the pharmacokinetics-pharmacodynamics (PK-PD) of
      tazobactam in combination with ceftolozane against an isogenic CTX-M-15-producing
      Escherichia coli triplet set, genetically engineered to transcribe different
      levels of blaCTX-M-15. The percentage of the dosing interval that tazobactam
      concentrations remained above a threshold (%Time>threshold) was identified as the
      PK-PD exposure measure that was most closely associated with efficacy. Moreover,
      the tazobactam concentration was dependent upon the enzyme transcription level.
      Given that the aforementioned strains were genetically engineered to transcribe a
      single beta-lactamase enzyme and that clinical isolates typically produce
      multiple beta-lactamase enzymes with various transcription levels, it is likely
      that the tazobactam threshold concentration is isolate/enzyme dependent. Our
      first objective was to characterize the relationship between the tazobactam
      %Time>threshold in combination with ceftolozane and efficacy using clinical
      isolates in an in vitro PK-PD infection model. Our second objective was to
      identify a translational relationship that would allow for the comodeling across
      clinical isolates. The initial challenge panel included four well-characterized
      beta-lactamase-producing E. coli strains with variable enzyme expression and
      other resistance determinants. As evidenced by r(2) values of ranging from 0.90
      to 0.99 for each clinical isolate, the observed data were well described by
      fitted functions describing the relationship between the tazobactam
      %Time>threshold and change in log10 CFU from baseline; however, the data from the
      four isolates did not comodel well. The threshold concentration identified for
      each isolate ranged from 0.5 to 4 mg/liter. We identified an enabling
      translational relationship for the tazobactam threshold that allowed comodeling
      of all four clinical isolates, which was the product of the individual isolate's
      ceftolozane-tazobactam MIC value and 0.5. As evidenced by an r(2) value of 0.90,
      the transformed data were well described by a fitted function describing the
      relationship between tazobactam %Time>threshold and change in log10 CFU from
      baseline. Due to these findings, the challenge panel was expanded to include
      three well-characterized beta-lactamase-producing Klebsiella pneumoniae strains
      with variable enzyme expression and other resistance determinants. The
      translational relationship for the tazobactam threshold that allowed for the
      comodeling of the four E. coli isolates performed well for the expanded data set
      (seven isolates in total; four E. coli and three K. pneumoniae), as evidenced by
      an r(2) value of 0.84. This simple translational relationship is especially
      useful as it is directly linked to in vitro susceptibility test results, which
      are used to guide the clinician's choice of drug and dosing regimen. 

PMID- 24041896
TI  - Multidrug-resistant transporter mdr1p-mediated uptake of a novel antifungal
      compound.
AB  - The activity of many anti-infectious drugs has been compromised by the evolution
      of multidrug-resistant (MDR) pathogens. For life-threatening fungal infections,
      such as those caused by Candida albicans, overexpression of MDR1, which encodes
      an MDR efflux pump of the major facilitator superfamily (MFS), often confers
      resistance to chemically unrelated substances, including the most commonly used
      azole antifungals. As the development of new and efficacious antifungals has
      lagged far behind the growing emergence of resistant strains, it is imperative to
      develop strategies to overcome multidrug resistance. Previous advances have been
      mainly to deploy combinational therapy to restore azole susceptibility, which,
      however, requires coordination of two or more compounds. We observed a unique
      phenotype in which Mdr1p facilitates the uptake of a specific class of compounds.
      Among them, we describe a novel antifungal small molecule, bis[1,6-a:5',6'
      g]quinolizinium 8-methyl-salt (BQM) (U.S. patent application no.
      61/793,090,2013), that has potent and broad antifungal activity. Notably, BQM
      exploits the MDR phenotype in C. albicans to promote the inhibitory effect.
      Rather than causing an antagonism of MDR strains, it exhibits a highly
      potentiated activity against a collection of clinical isolates and lab strains
      that overexpress MDR1. The activity of BQM against MDR1-overexpressing isolates
      is due to its facilitated intracellular accumulation. Microarray comparisons
      showed an extensive upregulation of MDR1 as well as polyamine transporter genes
      in a fluconazole-resistant strain. We then demonstrated that the polyamine
      transporters augment the accumulation of BQM. Importantly, BQM had greater
      activity than fluconazole and itraconazole against various fungal pathogens,
      including MDR Aspergillus fumigatus. Thus, our findings offer a paradigm shift to
      overcome MDR and the promise of improving antifungal treatment, especially in MDR
      pathogens. 

PMID- 24041897
TI  - In vitro cross-linking of Mycobacterium tuberculosis peptidoglycan by L,D
      transpeptidases and inactivation of these enzymes by carbapenems.
AB  - The Mycobacterium tuberculosis peptidoglycan is cross-linked mainly by l,d
      transpeptidases (LDTs), which are efficiently inactivated by a single beta-lactam
      class, the carbapenems. Development of carbapenems for tuberculosis treatment has
      recently raised considerable interest since these drugs, in association with the
      beta-lactamase inhibitor clavulanic acid, are uniformly active against
      extensively drug-resistant M. tuberculosis and kill both exponentially growing
      and dormant forms of the bacilli. We have purified the five l,d-transpeptidase
      paralogues of M. tuberculosis (Mt1 to -5) and compared their activities with
      those of peptidoglycan fragments and carbapenems. The five LDTs were functional
      in vitro since they were active in assays of peptidoglycan cross-linking (Mt5),
      beta-lactam acylation (Mt3), or both (Mt1, Mt2, and Mt4). Mt3 was the only LDT
      that was inactive in the cross-linking assay, suggesting that this enzyme might
      be involved in other cellular functions such as the anchoring of proteins to
      peptidoglycan, as shown in Escherichia coli. Inactivation of LDTs by carbapenems
      is a two-step reaction comprising reversible formation of a tetrahedral
      intermediate, the oxyanion, followed by irreversible rupture of the beta-lactam
      ring that leads to formation of a stable acyl enzyme. Determination of the rate
      constants for these two steps revealed important differences (up to 460-fold)
      between carbapenems, which affected the velocity of oxyanion and acyl enzyme
      formation. Imipenem inactivated LDTs more rapidly than ertapenem, and both drugs
      were more efficient than meropenem and doripenem, indicating that modification of
      the carbapenem side chain could be used to optimize their antimycobacterial
      activity. 

PMID- 24041898
TI  - Carbapenemase-producing enterobacteriaceae in Spain in 2012.
AB  - We report the epidemiological impact of carbapenemase-producing
      Enterobacteriaceae (CPE) in Spain in 2012. Of the 237 carbapenemases detected,
      163 were from the OXA-48 group, 60 were from VIM-1, 8 were from KPC-2, 5 were
      from IMP, and 1 was from NDM-1. Interhospital spread of carbapenemase-producing
      Klebsiella pneumoniae was due to a limited number of multilocus sequence types
      (MLST) and carbapenemase types, including ST15-VIM-1, ST11-OXA-48, ST405-OXA-48,
      ST101-KPC-2, and ST11-VIM-1. The number of CPE cases in Spain has increased
      sharply in recent years, due mainly to the emergence of OXA-48. 

PMID- 24041899
TI  - National prevalence of resistance to third-generation cephalosporins in
      Escherichia coli isolates from layer flocks in France.
AB  - Resistance of Escherichia coli to third-generation cephalosporin (3GC) in fecal
      samples representative of French egg production was studied. The susceptibility
      to cefotaxime of E. coli isolates obtained by culture on nonselective media was
      determined. Twenty-two nonsusceptible isolates were obtained (7.51%; 95%
      confidence interval, 4.49 to 10.54%), the majority of which came from young
      birds. Most isolates carried a blaCTX-M-1 group gene, and a few carried a blaCMY
      2-like gene. Control of 3GC resistance in laying hens is needed. 

PMID- 24041900
TI  - Predicting in vivo efficacy of therapeutic bacteriophages used to treat pulmonary
      infections.
AB  - The potential of bacteriophage therapy to treat infections caused by antibiotic
      resistant bacteria has now been well established using various animal models.
      While numerous newly isolated bacteriophages have been claimed to be potential
      therapeutic candidates on the basis of in vitro observations, the parameters used
      to guide their choice among billions of available bacteriophages are still not
      clearly defined. We made use of a mouse lung infection model and a bioluminescent
      strain of Pseudomonas aeruginosa to compare the activities in vitro and in vivo
      of a set of nine different bacteriophages (PAK_P1, PAK_P2, PAK_P3, PAK_P4,
      PAK_P5, CHA_P1, LBL3, LUZ19, and PhiKZ). For seven bacteriophages, a good
      correlation was found between in vitro and in vivo activity. While the remaining
      two bacteriophages were active in vitro, they were not sufficiently active in
      vivo under similar conditions to rescue infected animals. Based on the
      bioluminescence recorded at 2 and 8 h postinfection, we also define for the first
      time a reliable index to predict treatment efficacy. Our results showed that the
      bacteriophages isolated directly on the targeted host were the most efficient in
      vivo, supporting a personalized approach favoring an optimal treatment. 

PMID- 24041902
TI  - Pharmacokinetic-pharmacodynamic analyses for efficacy of ceftaroline fosamil in
      patients with community-acquired bacterial pneumonia.
AB  - Pharmacokinetic-pharmacodynamic (PK-PD) analyses for efficacy using phase III
      trial data from patients treated with a ceftaroline fosamil dosing regimen of 600
      mg intravenously (i.v.) every 12 h (q12h) for 5 to 7 days for community-acquired
      bacterial pneumonia (CABP) were conducted. High clinical and microbiological
      success rates (84.7 and 86.3%, respectively) and percentages of time during the
      dosing interval that free-drug steady-state concentrations remained above the MIC
      (f%T>MIC) (98.4% had f%T>MIC values of >=63.3) were observed among 124
      microbiologically evaluable patients. As a result, significant PK-PD
      relationships could not be identified. These data provide support for the use of
      a ceftaroline fosamil dosing regimen of 600 mg i.v. q12h to treat patients with
      CABP. 

PMID- 24041901
TI  - Characterization of potential drug targets farnesyl diphosphate synthase and
      geranylgeranyl diphosphate synthase in Schistosoma mansoni.
AB  - Schistosomiasis affects over 200 million people worldwide, with over 200,000
      deaths annually. Currently, praziquantel is the only drug available against
      schistosomiasis. We report here that Schistosoma mansoni farnesyl diphosphate
      synthase (SmFPPS) and geranylgeranyl diphosphate synthase (SmGGPPS) are potential
      drug targets for the treatment of schistosomiasis. We expressed active,
      recombinant SmFPPS and SmGGPPS for subsequent kinetic characterization and
      testing against a variety of bisphosphonate inhibitors. Recombinant SmFPPS was
      found to be a soluble 44.2-kDa protein, while SmGGPPS was a soluble 38.3-kDa
      protein. Characterization of the substrate utilization of the two enzymes
      indicates that they have overlapping substrate specificities. Against SmFPPS,
      several bisphosphonates had 50% inhibitory concentrations (IC50s) in the low
      micromolar to nanomolar range; these inhibitors had significantly less activity
      against SmGGPPS. Several lipophilic bisphosphonates were active against ex vivo
      adult worms, with worm death occurring over 4 to 6 days. These results indicate
      that FPPS and GGPPS could be of interest in the context of the emerging
      resistance to praziquantel in schistosomiasis therapy. 

PMID- 24041903
TI  - Identification of novel genes responsible for overexpression of ampC in
      Pseudomonas aeruginosa PAO1.
AB  - The development of resistance to antipseudomonal penicillins and cephalosporins
      mediated by the chromosomal ampC gene in Pseudomonas aeruginosa is of clinical
      importance. We isolated piperacillin-resistant mutants derived from P. aeruginosa
      PAO1 and analyzed two mutants that had an insertion in mpl and nuoN. One mutant,
      YT1677, was resistant to piperacillin and ceftazidime and had an insertion in
      mpl, which encodes UDP-N-acetylmuramate:l-alanyl-gamma-d-glutamyl-meso
      diaminopimelate ligase. The other mutant, YT7988, showed increased MICs of
      piperacillin, ceftazidime, cefepime, and cefoperazone, and the insertion was
      mapped to nuoN, which encodes NADH dehydrogenase I chain N. Complementation
      experiments demonstrated that these mutations resulted in higher levels of
      resistance to beta-lactams. The expression of genes reported to be involved in
      beta-lactam resistance was examined by real-time PCR in YT1677 and YT7988
      mutants. Overexpression was observed for only ampC, and other genes were
      expressed normally. Deletion of the ampR gene in YT1677 and YT7988 resulted in
      decreased expression of ampC, indicating that the mutations in YT1677 and YT7988
      affected the expression of ampC through the function of AmpR. 

PMID- 24041904
TI  - Discovery of inhibitors of 4'-phosphopantetheine adenylyltransferase (PPAT) to
      validate PPAT as a target for antibacterial therapy.
AB  - Inhibitors of 4'-phosphopantetheine adenylyltransferase (PPAT) were identified
      through high-throughput screening of the AstraZeneca compound library. One
      series, cycloalkyl pyrimidines, showed inhibition of PPAT isozymes from several
      species, with the most potent inhibition of enzymes from Gram-positive species.
      Mode-of-inhibition studies with Streptococcus pneumoniae and Staphylococcus
      aureus PPAT demonstrated representatives of this series to be reversible
      inhibitors competitive with phosphopantetheine and uncompetitive with ATP,
      binding to the enzyme-ATP complex. The potency of this series was optimized using
      structure-based design, and inhibition of cell growth of Gram-positive species
      was achieved. Mode-of-action studies, using generation of resistant mutants with
      targeted sequencing as well as constructs that overexpress PPAT, demonstrated
      that growth suppression was due to inhibition of PPAT. An effect on bacterial
      burden was demonstrated in mouse lung and thigh infection models, but further
      optimization of dosing requirements and compound properties is needed before
      these compounds can be considered for progress into clinical development. These
      studies validated PPAT as a novel target for antibacterial therapy. 

PMID- 24041905
TI  - Tools for characterizing bacterial protein synthesis inhibitors.
AB  - Many antibiotics inhibit the growth of sensitive bacteria by interfering with
      ribosome function. However, discovery of new protein synthesis inhibitors is
      curbed by the lack of facile techniques capable of readily identifying antibiotic
      target sites and modes of action. Furthermore, the frequent rediscovery of known
      antibiotic scaffolds, especially in natural product extracts, is time-consuming
      and expensive and diverts resources that could be used toward the isolation of
      novel lead molecules. In order to avoid these pitfalls and improve the process of
      dereplication of chemically complex extracts, we designed a two-pronged approach
      for the characterization of inhibitors of protein synthesis (ChIPS) that is
      suitable for the rapid identification of the site and mode of action on the
      bacterial ribosome. First, we engineered antibiotic-hypersensitive Escherichia
      coli strains that contain only one rRNA operon. These strains are used for the
      rapid isolation of resistance mutants in which rRNA mutations identify the site
      of the antibiotic action. Second, we show that patterns of drug-induced ribosome
      stalling on mRNA, monitored by primer extension, can be used to elucidate the
      mode of antibiotic action. These analyses can be performed within a few days and
      provide a rapid and efficient approach for identifying the site and mode of
      action of translation inhibitors targeting the bacterial ribosome. Both
      techniques were validated using a bacterial strain whose culture extract,
      composed of unknown metabolites, exhibited protein synthesis inhibitory activity;
      we were able to rapidly detect the presence of the antibiotic chloramphenicol. 

PMID- 24041907
TI  - The foreign doctors: the language issue.

PMID- 24041906
TI  - Biological evaluation of benzothiazole ethyl urea inhibitors of bacterial type II
      topoisomerases.
AB  - The type II topoisomerases DNA gyrase (GyrA/GyrB) and topoisomerase IV
      (ParC/ParE) are well-validated targets for antibacterial drug discovery. Because
      of their structural and functional homology, these enzymes are amenable to dual
      targeting by a single ligand. In this study, two novel benzothiazole ethyl urea
      based small molecules, designated compound A and compound B, were evaluated for
      their biochemical, antibacterial, and pharmacokinetic properties. The two
      compounds inhibited the ATPase activity of GyrB and ParE with 50% inhibitory
      concentrations of <0.1 MUg/ml. Prevention of DNA supercoiling by DNA gyrase was
      also observed. Both compounds potently inhibited the growth of a range of
      bacterial organisms, including staphylococci, streptococci, enterococci,
      Clostridium difficile, and selected Gram-negative respiratory pathogens. MIC90s
      against clinical isolates ranged from 0.015 MUg/ml for Streptococcus pneumoniae
      to 0.25 MUg/ml for Staphylococcus aureus. No cross-resistance with common drug
      resistance phenotypes was observed. In addition, no synergistic or antagonistic
      interactions between compound A or compound B and other antibiotics, including
      the topoisomerase inhibitors novobiocin and levofloxacin, were detected in
      checkerboard experiments. The frequencies of spontaneous resistance for S. aureus
      were <2.3 * 10(-10) with compound A and <5.8 * 10(-11) with compound B at
      concentrations equivalent to 8* the MICs. These values indicate a multitargeting
      mechanism of action. The pharmacokinetic properties of both compounds were
      profiled in rats. Following intravenous administration, compound B showed
      approximately 3-fold improvement over compound A in terms of both clearance and
      the area under the concentration-time curve. The measured oral bioavailability of
      compound B was 47.7%. 

PMID- 24041908
TI  - Plasma concentration of IL-6 and TNF-alpha and its relationship with zincemia in
      obese women.
AB  - OBJECTIVE: In obesity, the excessive adipose tissue increases the synthesis of
      inflammatory cytokines, which appear to alter the metabolism of minerals, such as
      zinc. However, the mechanisms involved remain unclear. This study investigated
      whether the concentrations of interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha) in plasma can to influence biochemical parameters of zinc in
      obese women. METHODS: Seventy-six pre-menopausal women, aged between 20 and 50
      years, were divided into two groups: the case group, composed of obese women
      (n=37) and the control group, composed of non-obese women (n=39). Analysis of the
      plasmatic and erythrocytary zinc, and plasmatic cytokines were conducted by flame
      atomic absorption spectrophotometry and by ELISA, respectively. RESULTS: The
      plasmatic zinc and concentrations of IL-6 in plasma did not show significant
      differences between obese women and controls (p>0.05). The erythrocytary zinc was
      36.4 +/- 15.0 MUg/gHb in the case group, and 45.4 +/- 14.3 MUg/gHb (p=0.025) in
      the control group. The concentrations of TNF-alpha in plasma were 42.0 +/- 11.9
      pg/mL and 19.0 +/- 1.0 pg/mL in obese women and in controls, respectively
      (p<0.001). The plasmatic zinc had a significant negative correlation with the
      values of TNFalpha (r=-0.44, p=0.015). CONCLUSION: Obese women presented lower
      concentrations of erythrocytary zinc than the control group. The study
      demonstrated a probable influence of the inflammatory process on metabolism of
      zinc in obese patients.

PMID- 24041909
TI  - Cost-effectiveness of the vaccine against human papillomavirus in the Brazilian
      Amazon region.
AB  - OBJECTIVE: To assess the cost-utility of the human papillomavirus (HPV)
      vaccination on the prevention of cervical cancer in the Brazilian Amazon region.
      METHODS: A Markov cohort model was developed to simulate the natural evolution of
      HPV and its progress to cervical cancer, considering the current preventive
      programs and treatment costs. The one-year transition probabilities were mainly
      based on empirical data of local and national studies. The model evaluated the
      addition of the vaccine to three cervical cancer-screening scenarios (0, 3 or 10
      exams throughout life). RESULTS: The scenario of three Pap tests resulted in
      satisfactory calibration (base case). The addition of HPV vaccination would
      reduce by 35% the incidence of cervical cancer (70% vaccination coverage). The
      incremental cost-effectiveness ratio was US$ 825 for each quality-adjusted life
      year gained. The sensitivity analysis confirms the robustness of this result, and
      duration of immunity was the parameter with greater variation in incremental cost
      effectiveness ratio. CONCLUSION: Vaccination has a favorable profile in terms of
      cost-utility, and its inclusion in the immunization schedule would result in a
      substantial reduction in incidence and mortality of invasive cervical cancer in
      the Brazilian Amazon region.

PMID- 24041910
TI  - Hepatocellular carcinoma: epidemiology, biology, diagnosis, and therapies.
AB  - Hepatocellular carcinoma is the fifth most common cancer in men and the seventh
      in women, as is diagnosed in more than half a million individuals worldwide every
      year. In Portugal, its incidence and mortality rates are low compared to other
      types of cancers. In Brazil, in the city of Sao Paulo, according to data released
      by the Brazilian Unified Health System (Sistema Unico de Saude - SUS), the
      incidence of primary liver cancer was 2.07/100,000 inhabitants. Although the vast
      majority of cases (85%) mainly affect developing countries, especially where
      infection by hepatitis B virus (HBV) is endemic, the incidence in developed
      countries is increasing. This pathology is associated with several risk factors,
      not only environmental but also genetic, generating an increasing interest in
      attaining a better understanding of this disease, which is still associated with
      very late diagnosis and poor prognosis. Of the available treatments, few patients
      benefit from their scanty advantages, increasingly stimulating research of new
      forms of treatment against this disease. This review aimed to briefly but fully
      identify risk factors, molecular and biochemical pathways, pathophysiology,
      diagnosis, and possible clinical approaches of hepatocellular carcinoma. 

PMID- 24041911
TI  - Image analysis with the computer vision system and the consumer test in
      evaluating the appearance of Lucanian dry sausage.
AB  - The object of the investigation was the Lucanian dry sausage appearance, meant as
      color and visible fat ratio. The study was carried out on dry sausages produced
      in 10 different salami factories and seasoned for 18 days on average. We studied
      the effect of the raw material origin (5 producers used meat bought from the
      market and other 5 producers used meat from pigs bred in their farms) and of the
      salami factories or brands on meat color, fat color and visible fat ratio in dry
      sausages. The sausages slices were photographed and the images were analysed with
      the computer vision system to measure the changes in the colorimetric
      characteristics L*, a*, b*, hue and chroma and in the visible fat area ratio. The
      last parameter was assessed on the slice surface using image binarization. A
      consumer test was conducted to determine the relationship between the perception
      of visible fat on the sausage slice surface and acceptability and preference of
      this product. The consumers were asked to look carefully at the 6 sausages slices
      in a photo, minding the presence of fat, and to identify (a) the slices they
      considered unacceptable for consumption and (b) the slice they preferred. The
      results show that the color of the sausage lean part varies in relation to the
      raw material employed and to the producer or brand (P<0.001). Besides, the
      sausage meat color is not uniform in some salami factories (P<0.05-0.001). In all
      salami factories the sausages show a high uniformity in fat color. The visible
      fat ratio of the sausages slices is higher (P<0.001) in the product from salami
      factories without pig-breeding farm. The fat percentage is highly variable
      (P<0.001) among the sausages of each salami factory. On the whole, the product
      the consumers consider acceptable and is inclined to eat has a low fat percentage
      (P<0.001). Our consumers (about 70%) prefer slices which are leaner (P<0.001).
      Women, in particular, show a higher preference for the leanest (P<0.001).

PMID- 24041912
TI  - Genetic polymorphism of 21 non-CODIS STR loci in the Chinese Mongolian ethnic
      minority.
AB  - In this research, we investigated the allele frequencies and forensic parameters
      of 21 non-, CODIS short tandem repeat (STR) loci (D6S474, D12ATA63, D22S1045,
      D10S1248, D1S1677, D11S4463, D1S1627, D3S4529, D2S441, D6S1017, D4S2408, D19S433,
      D17S1301, D1GATA113, D18S853, D20S482, D14S1434, D9S1122, D2S1776, D10S1435 and
      D5S2500) among 523 unrelated, Chinese Mongolians in the city of Tongliao, Horqin
      district, Inner Mongolia Autonomous Region. 

PMID- 24041913
TI  - Linguistic isolates in Portugal: insights from the mitochondrial DNA pattern.
AB  - Miranda do Douro, located in the northeastern region of Portugal, has notable
      characteristics not only from a geographic or naturalistic point of view, but
      also from a cultural perspective. A remarkable one is the coexistence of two
      different languages: Portuguese and Mirandese, the second being an Astur-Leonese
      dialect. The current persistence of the Astur-Leonese dialect in this population
      falls on the singularity of the region: relative isolation, implying difficulties
      to communicate with other Portuguese regions, while the same location facilitated
      the establishment of social and commercial relationships with adjacent Spanish
      territories, origin of the Astur-Leonese language. The objective of this study
      was to characterize the population from Miranda through the analysis of maternal
      lineages in order to evaluate whether its mitochondrial DNA diversity fitted the
      patterns previously reported for other populations from the Iberian Peninsula.
      Viewing that, the entire control region of mitochondrial DNA from 121 individuals
      was examined. Miranda showed a haplogroup composition usual for a Western
      European population, in the sense that as high as 63.6% of sequences belonged to
      macro-haplogroup R0. Lineages ascribed to have an African (L2a and L1b) origin,
      were detected, but reaching an amount commonly found in Portugal. Miranda also
      presented a few haplogroups typically found in Jewish populations, while rarely
      observed in other Iberian populations. The finding can be explained by gene flow
      with crypto-Jew communities that since long are known to be established in the
      region where Miranda is located. In Miranda, both genetic and nucleotide
      diversities presented low values (0.9292 +/- 0.0180 and 0.01101 +/- 0.00614
      respectively) when compared to populations from its micro-geographical framework,
      which constitute a sign of population isolation that certainly provided
      conditions for the survival of the Astur-Leonese dialect in the region.

PMID- 24041914
TI  - Effect of Optison on pulmonary artery systolic pressure and pulmonary vascular
      resistance.
AB  - Ultrasound contrast agent safety has received recent attention based on reports
      of associated serious adverse events. The US Food and Drug Administration
      requested this postmarketing study of the effects of Optison on pulmonary
      hemodynamics. The aim of this study was to compare Optison and a placebo for
      effects on pulmonary artery systolic pressure (PASP) and pulmonary vascular
      resistance (PVR) during right-sided cardiac catheterization. This was a single
      blind, crossover, placebo-controlled, multicenter study of Optison in subjects
      referred for clinically indicated cardiac catheterization. Based on screening
      echocardiographic PASP, subjects were assigned to 1 of 2 strata (1 = normal PASP
      [<=35 mm Hg] and 2 = elevated PASP [>35 mm Hg]), in which they were randomized to
      treatment arm A (intravenous 0.5 ml Optison and then intravenous 0.5 ml placebo
      [5% dextrose] 15 minutes later) or arm B (intravenous 0.5 ml placebo [5%
      dextrose] and then 0.5 ml Optison 15 minutes later). Baseline pulmonary
      hemodynamics were obtained within 60 minutes before the first injection and 2, 6,
      and 10 minutes after each injection. Thirty patients each received their assigned
      treatments. There were no clinically relevant increases from baseline in mean
      PASP or PVR (Wood units) in either stratum alone or the combined strata. There
      were no serious adverse events. In conclusion, there is no change in PASP or PVR
      after intravenous injection of Optison at a clinically relevant dose in patients
      with normal or elevated baseline PASP.

PMID- 24041915
TI  - Complications of Celect, Gunther tulip, and Greenfield inferior vena cava filters
      on CT follow-up: a single-institution experience.
AB  - PURPOSE: To evaluate and compare the rates of complications on follow-up computed
      tomography (CT) studies of patients with Celect, Gunther Tulip, and Greenfield
      inferior vena cava (IVC) filters. MATERIALS AND METHODS: Retrospective review of
      CT studies obtained 0-1,987 days after infrarenal placement of an IVC filter
      identified 255 Celect, 160 Tulip, and 50 Greenfield filters. Follow-up CT studies
      were independently evaluated by two observers for IVC perforation, contact with
      adjacent organs, and filter fracture. Multivariate analysis was performed to
      identify factors associated with higher rates of IVC perforation, including age,
      IVC diameter, sex, and history of malignancy. RESULTS: IVC perforation was
      observed in 126 of 255 Celect filters (49%) with a mean follow-up of 277 days, 69
      of 160 Tulip filters (43%) with a mean follow-up of 437 days, and one of 50
      Greenfield filters (2%) with a mean follow-up of 286 days. A significantly higher
      IVC perforation rate was observed in women (45.5%) compared with men (30.8%; P =
      .002) and in patients with a history of malignancy (43.7%) compared with patients
      with no history of malignancy (29.9%; P < .001). Filter fracture was rare,
      observed in two of 255 Celect filters (0.8%), one of 160 Tulip filters (0.6%),
      and none of 50 Greenfield filters. CONCLUSIONS: No significant difference was
      observed in IVC perforation rate between Celect and Tulip filters. Greenfield
      filters had a significantly lower rate of IVC perforation than Celect and Tulip
      filters. Higher IVC perforation rates were observed in women and patients with a
      history of malignancy.

PMID- 24041916
TI  - Reliability of the clinical examination in the diagnosis of neurogenic versus
      vascular claudication.
AB  - BACKGROUND CONTEXT: As research increasingly challenges the diagnostic accuracy
      of advanced imaging for lumbar spinal stenosis, the impression gleaned from the
      office evaluation becomes more important. Neurogenic claudication is a hallmark
      of lumbar spinal stenosis, but the reliability of clinical impression of
      claudication has not been studied. PURPOSE: To determine the reliability of the
      clinical examination for neurogenic claudication in an idealized setting. STUDY
      DESIGN: Prospective masked controlled trial. PATIENT SAMPLE: Persons aged 55 to
      90 years were recruited to form three groups: those offered surgery for spinal
      stenosis by academic spine surgeons, those who had peripheral vascular symptoms
      and positive ankle-brachial index (ABI), and those who were asymptomatic. All
      were extensively screened against confounding diseases. Forty-three neurogenic,
      12 vascular, and 35 asymptomatic recruits were tested. OUTCOME MEASURES: Clinical
      impression of neurogenic claudication. METHODS: A neurosurgeon and a vascular
      surgeon, masked to each other's findings, imaging, and recruitment status,
      performed a codified but unconstrained comprehensive spine and vascular history
      and physical examination for each subject. The surgeon's impression was recorded.
      RESULTS: Masked surgeons strongly agreed with the recruitment diagnosis
      (neurosurgeon kappa 0.761, vascular surgeon kappa 0.803, both p<.001) and with
      each other (kappa 0.717, p<.001). However, disagreements did occur between
      examiners and recruitment diagnosis (neurosurgeon n=13 cases, vascular surgeon
      n=10) and between examiners (n=14 cases). Pain level and marginally some measures
      of disability related to the agreement, but specific aspects of the physical
      examination, showed poor interrater reliability and did not contribute to the
      agreement. CONCLUSIONS: The clinical impression of neurogenic claudication is a
      reliable construct. The history, but not the poorly reproduced physical
      examination, contributes to reliability. The level of disagreement between
      experts in this simplified, yet severely involved, population raises concern
      about the risk of misdiagnosis in individual cases. Thus, surgical and other
      consequential decisions about diagnosis may require ancillary tests such as
      electromyography or ABI.

PMID- 24041917
TI  - Spontaneous regression of posterior epidural migrated lumbar disc fragments: case
      series.
AB  - BACKGROUND CONTEXT: Posterior epidural migrated lumbar disc fragments is an
      extremely rare disorder. Surgical treatment was performed in all reported cases.
      To the best of our knowledge, there are no reported cases of the use of
      conservative treatment for posterior epidural migrated lumbar disc fragments.
      PURPOSE: To report the possibility of a spontaneous regression of posterior
      epidural migrated lumbar disc fragments. STUDY DESIGN: Case series. METHODS: Four
      patients with posterior epidural migrated lumbar disc fragments were treated at
      Karatsu Red Cross Hospital between April 2008 and August 2010. Spontaneous
      regression of the posterior epidural migrated lumbar disc fragments with relief
      of symptoms was observed on magnetic resonance imaging (MRI) in three cases.
      Another patient underwent surgical treatment. The present and previously reported
      cases of posterior epidural migrated lumbar disc fragments were analyzed with
      respect to patient age, imaging features on MRI, the level of the lesion,
      clinical symptoms, treatment, and outcomes. RESULTS: Conservative treatment was
      successful, and spontaneous lesion regression was seen on MRI with symptom relief
      in three cases. CONCLUSIONS: Although posterior epidural migrated lumbar disc
      fragment cases are generally treated surgically, the condition can regress
      spontaneously over time, as do sequestrated disc fragments. Spontaneous
      regression of lumbar disc herniations is a widely accepted observation at
      present. Posterior epidural migrated lumbar disc fragments fall under the
      sequestrated type of disc herniation. In fact, the course of treatment for
      posterior epidural migrated lumbar disc fragments should be determined based on
      the symptoms and examination findings, as in cases of ordinary herniation.
      However, providing early surgical treatment is important if the patient has acute
      cauda equina syndrome or the neurologic symptoms worsen over time.

PMID- 24041918
TI  - Anterior cervical decompression and fusion on neck range of motion, pain, and
      function: a prospective analysis.
AB  - BACKGROUND CONTEXT: Intractable cervical radiculopathy secondary to stenosis or
      herniated nucleus pulposus is commonly treated with an anterior cervical
      decompression and fusion (ACDF) procedure. However, there is little evidence in
      the literature that demonstrates the impact such surgery has on long-term range
      of motion (ROM) outcomes. PURPOSE: The objective of this study was to compare
      cervical ROM and patient-reported outcomes in patients before and after a 1, 2,
      or 3 level ACDF. STUDY DESIGN: Prospective, nonexperimental. PATIENT SAMPLE:
      Forty-six patients. OUTCOME MEASURES: The following were measured preoperatively
      and also at 3 and 6 months after ACDF: active ROM (full and painfree) in three
      planes (ie, sagittal, coronal, and horizontal), pain visual analog scale, Neck
      Disability Index, and headache frequency. METHODS: Patients undergoing an ACDF
      for cervical radiculopathy had their cervical ROM measured preoperatively and
      also at 3 and 6 months after the procedure. Neck Disability Index and pain visual
      analog scale values were also recorded at the same time. RESULTS: Both painfree
      and full active ROM did not change significantly from the preoperative
      measurement to the 3-month postoperative measurement (ps>.05); however, painfree
      and full active ROM did increase significantly in all three planes of motion from
      the preoperative measurement to the 6-month postoperative measurement regardless
      of the number of levels fused (ps<=.023). Visual analog scale, Neck Disability
      Index, and headache frequency all improved significantly over time (ps<=.017).
      CONCLUSIONS: Our results suggest that patients who have had an ACDF for cervical
      radiculopathy will experience improved ROM 6 months postoperatively. In addition,
      patients can expect a decrease in pain, an improvement in neck function, and a
      decrease in headache frequency.

PMID- 24041919
TI  - From obesity to substance abuse: therapeutic opportunities for 5-HT2C receptor
      agonists.
AB  - The recent US Food and Drug Administration (FDA) approval of the serotonin (5
      hydroxytryptamine, 5-HT) 5-HT2C receptor agonist lorcaserin for the treatment of
      obesity represents a new therapeutic drug class available to the clinic.
      Preclinical evidence supports the potential for this drug class to treat other
      related conditions such as substance abuse. In the present article we review this
      evidence and further suggest that overlapping neurobiological systems may
      contribute to an anti-addictive and anti-obesity profile. The availability of
      selective 5-HT2C agonists provides an opportunity to evaluate their potential as
      treatments for nicotine dependence or psychostimulant abuse, conditions for which
      there is significant medical need but only limited available treatment options. 

PMID- 24041920
TI  - Compound ICA-105574 prevents arrhythmias induced by cardiac delayed
      repolarization.
AB  - Impaired ventricular repolarization can lead to long QT syndrome (LQT), a
      proarrhythmic disease with high risk of developing lethal ventricular
      tachyarrhythmias. The compound ICA-105574 is a recently developed hERG activator
      and it enhances IKr current with very high potency by removing the channel
      inactivation. The present study was designed to investigate antiarrhythmic
      properties of ICA-105574. For comparison, the effects of another compound NS1643
      was in-parallel assessed, which also acts primarily to attenuate channel
      inactivation with moderate potency. We found that both ICA-105574 and NS1643
      concentration-dependently shortened action potential duration (APD) in
      ventricular myocytes, and QT/QTc intervals in isolated guinea-pig hearts. ICA
      105574, but not NS1643, completely prevented ventricular arrhythmias in intact
      guinea-pig hearts caused by IKr and IKs inhibitors, although both ICA-105574 and
      NS1643 could reverse the drug-induced prolongation of APD in ventricular
      myocytes. Reversing prolongation of QT/QTc intervals and antagonizing the
      increases in transmural dispersion of repolarization and instability of the QT
      interval induced by IKr and IKs inhibitors contributed to antiarrhythmic effect
      of ICA-105574. Meanwhile, ICA-105574 at higher concentrations showed a potential
      proarrhythmic risk in normal hearts. Our results suggest that ICA-105574 has more
      efficient antiarrhythmic activity than NS1643. However, its potential
      proarrhythmic risk implies that benefits and risks should be seriously taken into
      consideration for further developing this type of hERG activators. 

PMID- 24041921
TI  - Effect of metabotropic glutamate 5 receptor antagonists on morphine efficacy and
      tolerance in rats with neuropathic pain.
AB  - The metabotropic glutamate 5 (mGlu5) receptor is involved in both pain processing
      and modulation of u-opioid induced antinociception and antihyperalgesia. Systemic
      mGlu5 receptor antagonists 2-methyl-6-phenylethynylpyridine (MPEP) or 3-[(2
      methyl-1,3-thiazol-4-yl) ethynyl] pyridine (MTEP) provide antihyperalgesic
      effects in various pain models, but few studies have shown their interaction with
      morphine in neuropathic pain models. The aim of this study is to compare the
      effects of systemic and intrathecal MPEP/MTEP on morphine efficacy and tolerance
      in rats with chronic neuropathic pain. L5-6 spinal nerve ligation (SNL) was used
      to establish neuropathic pain model in rats. The Von Frey test and the hot water
      tail flick test were employed as behavior tests. Low, medium and high doses of
      MPEP/MTEP were tested for their effect on both acute morphine efficacy and
      chronic morphine tolerance. SNL provides sustained neuropathic pain on the
      ipsilateral hind paw of rats. Both systemic and intrathecal MPEP/MTEP had
      antiallodynia effects and boosted morphine's efficacy in a dose-dependent manner
      in the Von Frey tests but not in the tail flick tests. In fact, high doses of
      MTEP and MPEP attenuated morphine's antinociceptive effect in the latter test.
      After intrathecal chronic co-administration with morphine, low-doses of MTEP/MPEP
      attenuated morphine tolerance in both tests. Systemically, only MTEP attenuated
      morphine tolerance, and only in the Von Frey tests, not in the tail flick tests,
      whereas MPEP had no effect on morphine tolerance in either tests. The therapeutic
      use of mGlu5 receptor antagonists may have distinct effects in different pain
      models. 

PMID- 24041922
TI  - Tetrodotoxin-dependent effects of menthol on mouse gastric motor function.
AB  - Menthol, the main active constituent of peppermint oil, exerts gut spasmolytic
      effects, although its mechanism of action remains unclear. We investigated the
      effects of menthol on gastric emptying and spontaneous- or evoked- mechanical
      activity of whole murine stomach. Gastric emptying was calculated after i.p.
      administration of menthol (50mg/Kg). Responses induced by menthol on gastric
      intraluminal pressure and evoked-cholinergic contractions were analyzed in vitro.
      Menthol decreased the gastric emptying rate. In vitro, menthol (0.3-30 mM)
      produced a concentration-dependent relaxation of whole stomach, that was
      significantly reduced by tetrodotoxin or omega-conotoxin GVIA. The gastric
      relaxant responses were not affected by Nomega-nitro-L-arginine methyl ester,
      inhibitor of nitric oxide-synthase, apamin or [Lys1,Pro2,5,Arg3,4,Tyr6]
      vasoactive intestinal peptide (VIP)(7-28), a VIP receptor antagonist, but they
      were significantly antagonized by atropine or guanethidine, a blocker of
      adrenergic neurotransmission. The joint application of atropine and guanethidine
      did not produce any additive effects on menthol effects. Phentolamine, an alpha
      adrenoceptor antagonist, but not propranolol, a beta-adrenoceptor antagonist,
      significantly reduced menthol responses and the contemporary administration of
      both adrenergic antagonists did not produce additive effects. Menthol (1-100 MUM)
      produced a reduction of the electrically-evoked cholinergic contractions, which
      was prevented by guanethidine. Menthol did not affect the contractions induced by
      carbachol. In conclusion, menthol in mouse, is able to reduce the rate of gastric
      emptying and to relax the stomach in vitro. The latter effect appears due, almost
      in part, to neural mechanisms, with involvement of alpha-adrenoceptors leading to
      reduction of tonic ongoing release of acetylcholine.

PMID- 24041923
TI  - Protective effects of aliskiren on ischemia-reperfusion-induced renal injury in
      rats.
AB  - The protective effect of aliskiren on ischemia-reperfusion (I/R) injury in the
      heart and brain has been reported. Whether or not this protective effect extends
      into the alleviation of renal I/R injury is not known. Therefore, we investigated
      the protective effect of aliskiren in the kidney in this study. Sprague-Dawley
      rats were randomly divided into four groups: sham control group; sham control
      with aliskiren pretreatment; I/R group and I/R with aliskiren pretreatment.
      Aliskiren (3mg/kg) or vehicle was administrated intravenously via vena cava.
      Blood samples and the left kidneys were then collected to check for renal
      function, angiotensin II (Ang II), apoptosis and oxidative stress levels.
      Compared with the sham rats, serum creatinine (SCR) and blood urea nitrogen (BUN)
      were significantly increased in the I/R rats, accompanied by histopathological
      damage to the kidney, which included tubular cell swelling, desquamation, and
      cast formation. There were also more apoptotic cells and leukocyte infiltration
      in the I/R rats than in the sham rats. Pretreatment with aliskiren ameliorated
      I/R induced renal injury, i.e. reduced SCR and BUN levels, ameliorated renal
      histopathological changes, and decreased the apoptosis of cells and leukocyte
      infiltration in kidney. I/R injury also decreased superoxide dismutase (SOD) and
      glutathione (GSH-reduced form) levels, which were blocked with the aliskiren
      pretreatment. Aliskiren pretreatment exerts a protective effect on
      ischemia/reperfusion injury in the kidney, via amelioration of oxidative stress,
      and reduction in leukocyte infiltration and cellular apoptosis. 

PMID- 24041924
TI  - Protective effect of moxonidine on ischemia/reperfusion-induced acute kidney
      injury through alpha2/imidazoline I1 receptor.
AB  - Enhancement of renal sympathetic nerve activity during renal ischemia and
      norepinephrine overflow from the kidney after reperfusion play important roles in
      the development of ischemic acute kidney injury. Recently, we have found that
      moxonidine, an alpha2/imidazoline Iota1-receptor agonist, has preventive effects
      on ischemic acute kidney injury by suppressing the excitation of renal
      sympathetic nervous system after reperfusion. In the present study, to clarify
      the renoprotective mechanisms of moxonidine (360 nmol/kg, i.v.) against ischemic
      acute kidney injury, we investigated the effect of intravenous (i.v.) and
      intracerebroventricular (i.c.v.) injection of efaroxan, an alpha2/Iota1 receptor
      antagonist, on the moxonidine-exhibited actions. Ischemic acute kidney injury was
      induced by clamping the left renal artery and vein for 45 min followed by
      reperfusion, 2 weeks after contralateral nephrectomy. The suppressive effect of
      moxonidine on enhanced renal sympathetic nerve activity during renal ischemia was
      not observed in the rat treated with either i.v. (360 nmol/kg) or i.c.v. (36
      nmol/kg) of efaroxan. Furthermore, i.v. injection of efaroxan eliminated the
      preventive effect of moxonidine on ischemia/reperfusion-induced kidney injury and
      norepinephrine overflow, and i.c.v. injection of efaroxan did not completely
      inhibit the moxonidine's effects. These results indicate that moxonidine prevents
      the ischemic kidney injury by sympathoinhibitory effect probably via alpha2/Iota1
      receptors in central nervous system and by suppressing the norepinephrine
      overflow through alpha2/Iota1 receptors on sympathetic nerve endings.

PMID- 24041925
TI  - Upregulation of thrombomodulin expression by activation of farnesoid X receptor
      in vascular endothelial cells.
AB  - Thrombomodulin (TM) serves as a vasoprotective molecule on the surface of
      vascular endothelial cells (VECs) to maintain the endothelial microenvironment by
      suppressing cellular proliferation, adhesion and inflammatory responses.
      Farnesoid X receptor (FXR), a nuclear receptor (NR) and originally considered as
      a bile acid-activated transcriptional factor, not only regulates metabolism
      homeostasis, but also influences cholesterol transport, vascular tension, and
      inflammation. Recent studies have shown that TM expression is upregulated by
      several NRs. However, it is unknown whether there is a link between FXR and TM.
      Our studies demonstrated that TM expression and activity were up-regulated by FXR
      activation in VECs. Reporter assays showed that FXR activation significantly
      enhanced the transcriptional activity of human TM gene promoter. Elecrophoretic
      mobility-shift and chromatin immunoprecipitation assays indicated that FXR
      induced TM expression by binding to a novel FXR-responsive element (FXRE), an
      inverted repeat DNA motif, IR8 (-503 AGGTCCtcccaaagTGCCCT-484) in the promoter
      region of TM gene. These results suggest that FXR may serve as a novel molecular
      target for manipulating TM expression and activity in VECs, which may be helpful
      for designing the therapeutic strategies to the treatment of associated diseases
      by targeting FXR/TM pathway. 

PMID- 24041926
TI  - Toll-like receptor (TLR) 7 decreases and TLR9 increases the airway responses in
      mice with established allergic inflammation.
AB  - Toll-like receptor (TLR) 7 and TLR9 recognise microbial products of viral
      descent. Since viruses are a common trigger of asthma exacerbations these TLRs
      have emerged as interesting therapeutic targets. Even though their effects on
      allergic inflammation have been evaluated in several models their effects on
      established allergic airway inflammation remains to be described. Therefore, mice
      with an on-going ovalbumin (OVA)-induced allergic airway inflammation were given
      R848 or CpG (TLR7 and TLR9 agonists, respectively) intranasally during four
      consecutive days. At day five, the R848 treatment had reduced OVA-induced airway
      hyperresponsiveness (measured as the increased resistance to methacholine),
      counteracted the accompanying influx of eosinophils and macrophages, and
      decreased the OVA-enhanced release of interleukin (IL)-5 and leukotriene (LT) B4
      in bronchoalveolar lavage fluid. CpG, which by itself caused airway
      hyperresponsiveness, did not influence the OVA-induced airway
      hyperresponsiveness, and release of IL-5 and LTB4, but decreased the OVA-induced
      influx of cells in bronchoalveolar lavage fluid, and increased the amount of pro
      inflammatory mediators like IL-12, CXCL1 and CXCL9. To conclude, TLR7 dampens the
      allergic airway reactivity and local inflammation, whereas TLR9 that causes
      airway hyperresponsiveness and increased cellular response per se, do generally
      not interfere with the effects induced by allergic inflammation. 

PMID- 24041927
TI  - Protective effects of sitagliptin on myocardial injury and cardiac function in an
      ischemia/reperfusion rat model.
AB  - The purpose of this study is to investigate the effects and the underlying
      mechanisms of sitagliptin pretreatment on myocardial injury and cardiac function
      in myocardial ischemia/reperfusion (I/R) rat model. The rat model of myocardial
      I/R was constructed by coronary occlusion. Rats were pretreated with sitagliptin
      (300 mg/kg/day) for 2 weeks, and then subjected to 30 min ischemia and 2h
      reperfusion. The release of lactate dehydrogenase (LDH) and creatine kinase-MB
      (CK-MB), cardiac function and cardiomyocyte apoptosis were evaluated. The levels
      of malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide
      dismutase (SOD) in heart and glucagon-like peptide-1 (GLP-1) level in plasma were
      measured. Western blot analysis was performed to detect the target proteins of
      sitagliptin. Our results showed that sitagliptin pretreatment decreased LDH and
      CK-MB release, and MDA level in I/R rats. More importantly, we revealed for the
      first time that sitagliptin pretreatment decreased cardiomyocyte apoptosis while
      increased the levels of GSH-Px and SOD in heart. Sitagliptin also increased GLP-1
      level and enhanced cardiac function in I/R rats. Furthermore, sitagliptin
      pretreatment up-regulated Akt(serine473) and Bad(serine136) phosphorylation,
      reduced the ratio of Bax/Bcl-2, and decreased expression levels of cleaved
      caspase-3 and caspase-3. Interestingly, the above observed effects of sitagliptin
      were all abolished when co-administered with GLP-1 receptor antagonist exendin-(9
      39) or PI3K inhibitor LY294002. Taken together, our data indicate that
      sitagliptin pretreatment could reduce myocardial injury and improve cardiac
      function in I/R rats by reducing apoptosis and oxidative damage. The underlying
      mechanism might be the activation of PI3K/Akt signaling pathway by GLP-1/GLP-1
      receptor.

PMID- 24041928
TI  - Anticancer activity of anandamide in human cutaneous melanoma cells.
AB  - Cannabinoids are implicated in the control of cell proliferation, but little is
      known about the role of the endocannabinoid system in human malignant melanoma.
      This study was aimed at characterizing the in vitro antitumor activity of
      anandamide (AEA) in A375 melanoma cells. The mRNA expression of genes that code
      for proteins involved in the metabolism and in the mechanism of AEA action was
      assessed by RT-PCR. Cell viability was tested using WST-1 assay and the apoptotic
      cell death was determined by measuring caspase 3/7 activities. A375 cells express
      high levels of fatty acid amide hydrolase (FAAH), cyclooxygenase (COX)-2,
      cannabinoid receptor 1 (CB1), transient receptor potential cation channel
      subfamily V member 1 (TRPV1) and G-protein-coupled receptor 55 (GPR55) genes. AEA
      induced a concentration-dependent cytotoxicity with an IC50 of 5.8 +/- 0.7 uM and
      such an effect was associated to a caspase-dependent apoptotic pathway. AEA
      cytotoxicity was potentiated by FAAH inhibition (2-fold increase, p<0.05) and
      mitigated by COX-2 or lipoxygenase (LOX) inhibition (5- and 3-fold decrease,
      respectively; p<0.01). Blocking CB1 receptors partially decreased AEA
      cytotoxicity, whereas selective antagonism on the TRPV1 barely affected the
      mechanism of AEA action. Finally, methyl-beta-cyclodextrin, a membrane
      cholesterol depletory, completely reversed the cytotoxicity induced by the
      selective GPR55 agonist, O-1602, and AEA. Overall, these findings demonstrate
      that AEA induces cytotoxicity against human melanoma cells in the micromolar
      range of concentrations through a complex mechanism, which involves COX-2 and LOX
      derived product synthesis and CB1 activation. Lipid raft modulation, probably
      linked to GPR55 activation, might also have a role.

PMID- 24041929
TI  - Guggulsterone regulates the function and expression of P-glycoprotein in rat
      brain microvessel endothelial cells.
AB  - Our previous studies found that guggulsterone could inhibit P-glycoprotein
      mediated multidrug resistance in P-glycoprotein over-expressed human cancer cell
      lines. However, the effects of guggulsterone on the ;P-glycoprotein function and
      expression in rat brain microvessel endothelial cells (rBMECs) are poorly
      understood. In the present study, we investigated whether guggulsterone has a
      modulative effect on the function and expression of P-glycoprotein in rBMECs.
      rhodamine 123 acts as a good substrate for P-glycoprotein, and agents that block
      P-glycoprotein have been found to increase the retention of rhodamine in cells.
      The results showed that the accumulation of rhodamine 123 in rBMECs was
      potentiated in a time-dependent manner after incubation with 30, 100 MUM
      guggulsterone (P<0.05). Efflux of intracellular rhodamine 123 was decreased in a
      time-dependent manner from after 30, 100 MUM guggulsterone treatment. The
      inhibitory effect of guggulsterone on P-glycoprotein function was reversible and
      remained at 120 min after removal of 30, 100 MUM guggulsterone from the medium.
      Further results showed that guggulsterone (30, 100 MUM) down-regulated the
      expression of P-glycoprotein, and had no influence on the expression of breast
      cancer resistance protein in rBMECs. In addition, the present study revealed that
      guggulsterone promoted the activity of P-glycoprotein ATPase in a dose-dependent
      manner. These results indicated that guggulsterone suppressed the function and
      expression of P-glycoprotein in rBMECs primary cultures.

PMID- 24041930
TI  - Coagulation factor Xa induces an inflammatory signalling by activation of
      protease-activated receptors in human atrial tissue.
AB  - Activated factor X (FXa) is an important player in the coagulation cascade
      responsible for thrombin generation, which is activated during atrial
      fibrillation. Increasing evidence suggests that FXa influences cell signalling in
      various cell types by activating protease-activated receptors (PARs). It is so
      far not known if molecular effects of FXa affect atrial signal transduction. To
      study the effects of FXa, human atrial tissue slices were cultivated with FXa up
      to 24h. Additionally, rapid pacing was applied at 4Hz to resemble atrial
      fibrillation. The inhibitory impact of FXa antagonist (Rivaroxaban), protease
      activated receptor 1 antagonist (SCH79797), and protease-activated receptor 2
      antagonist (GB83) were analysed under experimental conditions. The exposure of
      atrial tissue to FXa resulted in the 1.7 fold upregulation of PAR2-mRNA,
      activation of MAP kinases (ERK1/2) and NF-kappaB signalling. Furthermore FXa
      increased the expression of adhesion molecule ICAM-1 (1.82 +/- 0.20), chemokine
      IL-8 (1.94 +/- 0.20), as well as prothrombotic molecule PAI-1 (1.52 +/- 0.17).
      The combination of rapid pacing and FXa caused significant upregulation of PAR1
      (2.82 +/- 0.22), PAR2 (2.66 +/- 0.40), ICAM-1 (2.13 +/- 0.25), IL-8 (2.22 +/-
      0.24), LOX-1 (2.59 +/- 0.35), and PAI-1 (2.65 +/- 0.52) at the mRNA level.
      Rivaroxaban and GB83 prevented upregulation of PARs, ICAM-1, LOX-1, IL-8, and
      activation of MAP kinases. The elevation in the expression of PAI-1 was hindered
      in the presence of SCH79797, or Rivaroxaban. The present study indicates that FXa
      mediates inflammatory signalling in atrial tissue. Importantly, FXa and
      tachyarrhythmia act synergistically to increase expression of protease-activated
      receptors and inflammatory mediators. Rivaroxaban prevented effectively FXa
      induced molecular effects in human atrial tissue particularly during rapid
      pacing.

PMID- 24041932
TI  - ISO-1, a macrophage migration inhibitory factor antagonist, prevents N-methyl-D
      aspartate-induced retinal damage.
AB  - Macrophage migration inhibitory factor (MIF) has been shown to play an important
      role in a variety of inflammatory and immune-mediated diseases. The inflammatory
      responses contribute to retinal neuronal degeneration. However, the role of MIF
      in the progression of retinal degeneration has not yet been elucidated. In this
      study, we determined whether pharmacological inhibition of MIF protects against
      the retinal damage induced by N-methyl-D-aspartate (NMDA) in rats. Intravitreal
      injection of NMDA (200 nmol) resulted in (1) cell loss in the ganglion cell layer
      and reduction in the thickness of the inner plexiform layer, (2) an increase in
      apoptotic cells, (3) a decrease in parvalbumin-positive amacrine cells, (4)
      accumulation of leukocytes, and (5) microglia activation. Injection of (S,R)-3-(4
      hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1, 100
      nmol), a MIF antagonist, significantly attenuated these NMDA-induced responses.
      These findings suggest that ISO-1 exerts protective effects against retinal
      injuries and that MIF may be a target for neuroprotective intervention in retinal
      diseases associated with glutamate-induced excitotoxicity.

PMID- 24041931
TI  - The serotonin-2 receptor modulator, (-)-trans-PAT, decreases voluntary ethanol
      consumption in rats.
AB  - Serotonin (5-HT) 5-HT2C receptor agonists have shown promise as novel alcoholism
      pharmacotherapies, but developing selective agonists has been problematic. Female
      Sprague Dawley rats were given ethanol in a palatable gel vehicle during operant
      sessions. 5-HT2C receptor modulators (Ro60-0175, SB242,084, and (-)-trans-PAT)
      were administered before operant sessions. As a control for the effects of 5-HT2C
      receptor agonism on caloric intake, drugs were also tested using non-ethanol
      containing gelatin. Ro60-0175, a 5-HT2 family receptor agonist, decreased both
      ethanol and vehicle responding while (-)-trans-PAT, a 5-HT2C receptor agonist
      with 5-HT2A-2B receptor inverse agonist activity, selectively reduced only
      ethanol responding. The effect of 5-HT2C receptor agonists on self-administration
      after reinstatement of ethanol after a three week deprivation was also
      determined. (-)-trans-PAT eliminated increases in ethanol intake following
      ethanol deprivation whereas Ro60-0175 had no effect. These results emphasize the
      need for caloric controls and further support the idea that selective modulation
      of 5-HT2 family receptors is a potential pharmacotherapeutic approach in the
      treatment of alcoholism. 

PMID- 24041933
TI  - Adipogenesis: new insights into brown adipose tissue differentiation.
AB  - Confirmation of the presence of functional brown adipose tissue (BAT) in humans
      has renewed interest in investigating the potential therapeutic use of this
      tissue. The finding that its activity positively correlates with decreased BMI,
      decreased fat content, and augmented energy expenditure suggests that increasing
      BAT mass/activity or browning of white adipose tissue (WAT) could be a strategy
      to prevent or treat obesity and its associated morbidities. The challenge now is
      to find a safe and efficient way to develop this idea. Whereas BAT has being
      widely studied in murine models both in vivo and in vitro, there is an urgent
      need for human cellular models to investigate BAT physiology and functionality
      from a molecular point of view. In this review, we focus on the latest insights
      surrounding BAT development and activation in rodents and humans. Then, we
      discuss how the availability of murine models has been essential to identify BAT
      progenitors and trace their lineage. Finally, we address how this information can
      be exploited to develop human cellular models for BAT differentiation/activation.
      In this context, human embryonic stem and induced pluripotent stem cells-based
      cellular models represent a resource of great potential value, as they can
      provide a virtually inexhaustible supply of starting material for functional
      genetic studies, -omics based analysis and validation of therapeutic approaches.
      Moreover, these cells can be readily genetically engineered, opening the
      possibility of generating patient-specific cellular models, allowing the
      investigation of the influence of different genetic backgrounds on BAT
      differentiation in pathological or in physiological states. 

PMID- 24041934
TI  - Testing a two step nursing intervention focused on decreasing rehospitalizations
      and nursing home admission post discharge from acute care.
AB  - Older adults are at high risk of readmission on discharge from the Acute Medical
      and Emergency Department (ED). This study examines the effect of a two-stage
      nursing assessment and intervention to address older adults' uncompensated
      problems and thus intend to prevent readmission and functional decline. A
      randomized controlled study was conducted. Included were 271 patients aged 70 and
      over admitted to an ED. A brief standardized nursing assessment and intervention
      was carried out after discharge and at follow-up. No effect was found on
      readmission to hospital, admission to nursing home, or death but the intervention
      group was less likely to be at risk of depression after 180 days. Whether this
      method can be recommended needs further study as well as knowledge is needed as
      to the organization and to reveal older adults' experiences on follow-up after ED
      stay. 

PMID- 24041935
TI  - Migration of glial cells differentiated from neurosphere-forming neural
      stem/progenitor cells depends on the stiffness of the chemically cross-linked
      collagen gel substrate.
AB  - Substrate stiffness affects cell migration and spreading. Our study revealed that
      the stiffness of the cell-adhesive substrate affected the migration pattern of
      neural cells. We observed the migration of neural cells differentiated from
      neurosphere-forming neural stem/progenitor cells (NSPCs) on collagen gels with
      various degrees of stiffness achieved by chemical cross-linking. Both glial and
      neuronal cells broadly spread and migrated when stiff collagen gels (G'=5.5kPa,
      G"=0.2kPa) were used as the substrate. In contrast, the migration of glial cells
      was suppressed within the limited area on the soft collagen gels (G'=0.8kPa,
      G"=0.2kPa). Filopodia were rarely observed in glial cells on the soft collagen
      gels. Analysis of the intercellular distance between the closest neural cells
      after differentiation from NSPCs indicated that glial cells more broadly spread
      on the stiff collagen gels than on the soft gels. Immunocytochemical analysis
      showed that most of the migrated cells were glial cells, suggesting that
      migration of glial cells was dependent on the stiffness of substrate. 

PMID- 24041936
TI  - Phylogeny of the Elopomorpha (Teleostei): evidence from six nuclear and
      mitochondrial markers.
AB  - The Elopomorpha (eels and relatives) is a morphologically diverse group of
      predominantly marine teleost fishes comprising about 1000 species placed in 25
      families. It is one of the three major living teleost lineages along with the
      Osteoglossomorpha and Clupeocephala. Among a few morphological synapomorphies
      that have been offered as evidence for the monophyly of the Elopomorpha, the
      remarkable leptocephalus larvae stand out. Several studies aiming at
      reconstructing the elopomorph phylogeny using morphological or molecular
      characters led to inconsistent results. In this study, we have tested previous
      hypotheses regarding inter- and intra-relationships of the Elopomorpha using a
      multi-locus dataset composed of three nuclear and three mitochondrial genes. Our
      analyses were based on likelihood phylogenetic reconstruction methods using
      different character-weighting data matrices and gene partition schemes to assess
      reliability of our findings. Our results confirm the respective monophyly of the
      Elopomorpha, Osteoglossomorpha and Clupeocephala. The majority of our analyses
      identify the Elopomorpha as the sister group of a clade containing the rest of
      the Teleostei. Within the Elopomorpha, the Elopiformes is the sister group of the
      remaining taxa. The Albuliformes sensuForey et al. (1996) and the
      Notacanthiformes are never sister-taxa in our phylogenetic trees, in
      contradiction with the recent mitogenomic hypothesis and current classification.
      Our results place the Notacanthiformes as the sister group of the Anguilliformes,
      including Saccopharyngiformes. Among anguilliforms, the families Congridae and
      Muraenesocidae are not monophyletic. The recently discovered anguilliform "living
      fossil" family Protanguillidae is not the sister group of the remaining
      Anguilliformes, instead, the sister group of the Synaphobranchidae. Based on the
      results presented here, we propose a revised classification for the Elopomorpha,
      comprised of four orders, including a resurrected Notacanthiformes but
      surrendering the Saccopharyngiformes. Within Anguilliformes, we recognized four
      monophyletic suborders named Protanguilloidei, Muraenoidei, Anguilloidei, and
      Congroidei. 

PMID- 24041937
TI  - Facilitation of sodium intake by combining noradrenaline into the lateral
      parabrachial nucleus with prazosin peripherally.
AB  - Injections of noradrenaline into the lateral parabrachial nucleus (LPBN) increase
      arterial pressure and 1.8% NaCl intake and decrease water intake in rats treated
      with the diuretic furosemide (FURO) combined with a low dose of the angiotensin
      converting enzyme inhibitor captopril (CAP). In the present study, we
      investigated the influence of the pressor response elicited by noradrenaline
      injected into the LPBN on FURO+CAP-induced water and 1.8% NaCl intake. Male
      Holtzman rats with bilateral stainless steel guide-cannulas implanted into LPBN
      were used. Bilateral injections of noradrenaline (40 nmol/0.2 MUl) into the LPBN
      increased FURO+CAP-induced 1.8% NaCl intake (12.2+/-3.5, vs., saline: 4.2+/-0.8
      ml/180 min), reduced water intake and strongly increased arterial pressure (50+/
      7, vs. saline: 1+/-1 mmHg). The blockade of the alpha1 adrenoceptors with the
      prazosin injected intraperitoneally abolished the pressor response and increased
      1.8% NaCl and water intake in rats treated with FURO+CAP combined with
      noradrenaline injected into the LPBN. The deactivation of baro and perhaps volume
      receptors due to the cardiovascular effects of prazosin is a mechanism that may
      facilitate water and NaCl intake in rats treated with FURO+CAP combined with
      noradrenaline injected into the LPBN. Therefore, the activation of alpha2
      adrenoceptors with noradrenaline injected into the LPBN, at least in dose tested,
      may not completely remove the inhibitory signals produced by the activation of
      the cardiovascular receptors, particularly the signals that result from the extra
      activation of these receptors with the increase of arterial pressure.

PMID- 24041938
TI  - Segmental progression of cardinal motor symptoms in Parkinson's disease: a pilot
      study suggesting a practical approach to rate disease course in the early stages.
AB  - Little is known about the anatomical progression over the body segments of
      extrapyramidal signs in Parkinson's disease (PD); furthermore a great unmet need
      is the availability of instruments able to detect disease progression, even in
      the early phase. The purpose of this study is to demonstrate that assessing
      topographical distribution of the cardinal motor features of PD may significantly
      improve the evaluation of disease progression in the early stages. Forty-four
      drug-naive PD patients were included in the study. Presence or absence of
      bradykinesia, rest tremor and rigidity was derived from Unified Parkinson's
      disease rating scale part III (UPDRS-III) in five different anatomical segments:
      axial, right and left upper- and lower-limbs. Based on this approach, four new
      scores were computed evaluating the anatomical spread of the cardinal motor
      symptoms of PD on the five body segments over a 18-month follow-up period. The
      four new scores included: the Bradykinesia Segmental Score, the Tremor Segmental
      Score, the Rigidity Segmental Score, measuring the occurrence of each motor
      symptom in different segments and the Combined Segmental Score evaluating the
      occurrence of any motor symptom in different anatomical regions. Data were
      analyzed using a repeated measures analysis of variance. The Combined Segmental
      Score showed a significant progression over time whereas the Hoehn and Yahr and
      the UPDRS-III scores did not. We suggest that a simple approach evaluating the
      anatomical distribution of motor symptoms and their progression over the body
      segments may be a useful complement to the classical rating tools to assess
      progression in early PD. 

PMID- 24041939
TI  - Multiple source current steering--a novel deep brain stimulation concept for
      customized programming in a Parkinson's disease patient.

PMID- 24041940
TI  - A transcriptional and metabolic signature of primary aneuploidy is present in
      chromosomally unstable cancer cells and informs clinical prognosis.
AB  - Aneuploidy is invariably associated with poor proliferation of primary cells, but
      the specific contributions of abnormal karyotypes to cancer, a disease
      characterized by aneuploidy and dysregulated proliferation, remain unclear. In
      this study, I demonstrate that the transcriptional alterations caused by
      aneuploidy in primary cells are also present in chromosomally unstable cancer
      cell lines, but the same alterations are not common to all aneuploid cancers.
      Chromosomally unstable cancer lines and aneuploid primary cells also share an
      increase in glycolytic and TCA cycle flux. The biological response to aneuploidy
      is associated with cellular stress and slow proliferation, and a 70-gene
      signature derived from primary aneuploid cells was defined as a strong predictor
      of increased survival in several cancers. Inversely, a transcriptional signature
      derived from clonal aneuploidy in tumors correlated with high mitotic activity
      and poor prognosis. Together, these findings suggested that there are two types
      of aneuploidy in cancer: one is clonal aneuploidy, which is selected during tumor
      evolution and associated with robust growth, and the other is subclonal
      aneuploidy caused by chromosomal instability (CIN). Subclonal aneuploidy more
      closely resembles the stressed state of primary aneuploid cells, yet CIN is not
      benign; a subset of genes upregulated in high-CIN cancers predict aggressive
      disease in human patients in a proliferation-independent manner.

PMID- 24041941
TI  - [Predictive factors of response to erytrhocytapheresis in patients with
      biochemical iron overload with or without hereditary hemochromatosis type 1].
AB  - BACKGROUND AND OBJECTIVE: Progressive increase of iron stores leads to the
      development of varied diseases, some of them irreversible. Until now, phlebotomy
      has been the cornerstone in the treatment of iron overload. Nevertheless, each
      erytrhocytapheresis procedure removes more than twice the volume of red cells and
      iron than phlebotomy, allowing to achieve iron depletion in shorter time. Our aim
      was to describe clinical features and analytical tests parameters of patients
      with iron overload, to analyze global and subsets results, to suggest predictive
      factors of response and to evaluate security of the procedure. PATIENTS AND
      METHOD: Descriptive, longitudinal and prospective study of 663 procedures
      corresponding to 35 patients (December 2002 to October 2011). Response was
      defined as a serum ferritine value lower than 50 ng/mL during two months.
      Statistical analysis was done with SPSS((r)) v 17.0 and the minimum level of
      statistical significance was defined as p-value < 0,05. RESULTS: Seventy-seven
      percent of patients reached response with 11 (interquartile range 1-42)
      erytrhocytapheresis procedures and at 11 (1-108) months. Eighty-seven point five
      percent of patients who did not achieve response had their ferritine values
      reduced in more than 50%. The decrease of all iron metabolism parameters was
      statistically significant. Statistically significant predictive factors of
      response to erytrhocytapheresis were: patients younger than 60 years-old,
      hereditary hemochromatosis cases, and patients who had received treatment with
      phlebotomies prior to erytrhocytapheresis. CONCLUSIONS: Erytrhocytapheresis is a
      secure and effective procedure for iron depletion in patients with iron overload,
      especially in high risk hereditary hemochromatosis cases that do not respond to
      phlebotomies.

PMID- 24041942
TI  - Asthma.
AB  - Asthma is a heterogeneous group of conditions that result in recurrent,
      reversible bronchial obstruction. Although the disease can start at any age, the
      first symptoms occur during childhood in most cases. Asthma has a strong genetic
      component, and genome-wide association studies have identified variations in
      several genes that slightly increase the risk of disease. Asthma is often
      associated with increased susceptibility to infection with rhinoviruses and with
      changes in the composition of microbial communities colonising the airways, but
      whether these changes are a cause or consequence of the disease is unknown. There
      is currently no proven prevention strategy; however, the finding that exposure to
      microbial products in early life, particularly in farming environments, seems to
      be protective against asthma offers hope that surrogates of such exposure could
      be used to prevent the disease. Genetic and immunological studies point to
      defective responses of lung resident cells, especially those associated with the
      mucosal epithelium, as crucial elements in the pathogenesis of asthma. Inhaled
      corticosteroids continue to be the mainstay for the treatment of mild and
      moderate asthma, but limited adherence to daily inhaled medication is a major
      obstacle to the success of such therapy. Severe asthma that is refractory to
      usual treatment continues to be a challenge, but new biological therapies, such
      as humanised antibodies against IgE, interleukin 5, and interleukin 13, offer
      hope to improve the quality of life and long-term prognosis of severe asthmatics
      with specific molecular phenotypes. 

PMID- 24041943
TI  - Angiotensin II-independent angiotensin-(1-7) formation in rat hippocampus:
      involvement of thimet oligopeptidase.
AB  - The involvement and relevance of the renin-angiotensin system have been
      established clearly in cardiovascular diseases, and renin-angiotensin system
      involvement has also been investigated extensively in the central nervous system.
      Angiotensin II acts classically by binding to the AT1 and AT2 receptors. However,
      other pathways within the renin-angiotensin system have been described more
      recently, such as one in which angiotensin-(1-7) (Ang-(1-7)) binds to the
      receptor Mas. In the central nervous system specifically, it has been reported
      that this heptapeptide is involved in learning and memory processes that occur in
      central limbic regions, such as the hippocampus. Therefore, this prompted us to
      investigate the possible role of the Ang-(1-7)-receptor Mas pathway in epileptic
      seizures, which are also known to recruit limbic areas. In the present study, we
      show that Ang-(1-7) is the main metabolite of angiotensin I in rat hippocampi,
      and, strikingly, that thimet oligopeptidase is the main enzyme involved in the
      generation of Ang-(1-7). Furthermore, elevations in the levels of thimet
      oligopeptidase, Ang-(1-7), and of receptor Mas transcripts are observed in
      chronically stimulated epileptic rats, which suggest that the thimet
      oligopeptidase-Ang-(1-7)-receptor Mas axis may have a functional relevance in the
      pathophysiology of these animals. In summary, our data, which describe a new
      preferential biochemical pathway for the generation of Ang-(1-7) in the central
      nervous system and an increase in the levels of various elements of the related
      thimet oligopeptidase-Ang-(1-7)-receptor Mas pathway, unveil potential new roles
      of the renin-angiotensin system in central nervous system pathophysiology. 

PMID- 24041944
TI  - Angiotensin II type 2 receptor-mediated and nitric oxide-dependent renal
      vasodilator response to compound 21 unmasked by angiotensin-converting enzyme
      inhibition in spontaneously hypertensive rats in vivo.
AB  - Angiotensin II type 2 receptor (AT2R)-mediated vasodilation has been demonstrated
      in different vascular beds in vitro and in perfused organs. In vivo studies,
      however, consistently failed to disclose renal vasodilator responses to compound
      21, a selective AT2R agonist, even after angiotensin II type 1 receptor blockade.
      Here, we investigated in vivo whether angiotensin-converting enzyme inhibition,
      reducing endogenous angiotensin II levels, could unmask the effects of selective
      AT2R stimulation on blood pressure and renal hemodynamics in normotensive and
      hypertensive rats. After pretreatment with the angiotensin-converting enzyme
      inhibitor captopril, intravenous administration of compound 21 did not affect
      blood pressure and induced dose-dependent renal vasodilator responses in
      spontaneously hypertensive but not in normotensive rats. The D1 receptor agonist
      fenoldopam, used as positive control, reduced blood pressure and renal vascular
      resistance in both strains. The AT2R antagonist PD123319 and the nitric oxide
      synthase inhibitor L-NMMA (N(G)-monomethyl-L-arginine acetate) abolished the
      renal vasodilator response to compound 21 without affecting responses to
      fenoldopam. The cyclooxygenase inhibitor indomethacin partially inhibited the
      renal vascular response to compound 21, whereas the bradykinin B2 receptor
      antagonist icatibant was without effect. Angiotensin-converting enzyme inhibition
      unmasked a renal vasodilator response to selective AT2R stimulation in vivo,
      mediated by nitric oxide and partially by prostaglandins. AT2R may have a
      pathophysiological role to modulate renal hemodynamic effects of angiotensin II
      in the hypertensive state. 

PMID- 24041945
TI  - Salt, salt sensitivity, and the endothelium: a pathway to discovery of molecular
      mechanisms.

PMID- 24041946
TI  - Cerebral autoregulation of blood velocity and volumetric flow during steady-state
      changes in arterial pressure.
AB  - The validity of using transcranial Doppler measurement of cerebral blood flow
      velocity (CBFV) to assess cerebral autoregulation (CA) still is a concern. This
      study measured CBFV in the middle cerebral artery using transcranial Doppler and
      volumetric cerebral blood flow (CBF) in the internal carotid artery (ICA) using
      color-coded duplex ultrasonography to assess CA during steady-state changes in
      mean arterial pressure (MAP). Twenty-one healthy adults participated. MAP was
      changed stepwise by intravenous infusion of sodium nitroprusside and
      phenylephrine. Changes in CBFV, CBF, cerebrovascular resistance (CVR=MAP/CBF), or
      cerebrovascular resistance index (CVRi=MAP/CBFV) were measured to assess CA by
      linear regression analysis. The relationship between changes in ICA diameter and
      MAP was assessed. All values were normalized as percentage changes from baseline.
      Drug-induced changes in MAP were from -26% to 31%. Changes in CBFV and CVRi in
      response to MAP were linear, and the regression slopes were similar between
      middle cerebral artery and ICA. However, CBF in ICA remained unchanged despite
      large changes in MAP. Consistently, a steeper slope of changes in CVR relative to
      CVRi was observed (0.991 versus 0.804; P<0.05). The ICA diameter changed
      inversely in response to MAP (r=-0.418; P<0.05). These findings indicate that CA
      can be assessed with transcranial Doppler measurements of CBFV and CVRi in middle
      cerebral artery. However, it is likely to be underestimated when compared with
      the measurements of CBF and CVR in ICA. The inverse relationship between changes
      in ICA diameter and MAP suggests that large cerebral arteries are involved in CA.

PMID- 24041947
TI  - Transforming growth factor-beta regulates endothelial function during high salt
      intake in rats.
AB  - Previous studies have demonstrated that an increase in dietary NaCl (salt) intake
      stimulated endothelial cells to produce transforming growth factor-beta (TGF
      beta). The intent of the present study was to determine the functional
      significance of increased TGF-beta on endothelial cell function. Young Sprague
      Dawley rats were fed diets containing 0.3 or 8.0% NaCl for 2 days before
      treatment with a specific inhibitor of the TGF-beta receptor I/activin receptor
      like kinase 5 kinase, or vehicle for another 2 days. At day 4 of study,
      endothelial phosphorylated Smad2 (S465/467) increased and phosphatase and tensin
      homologue deleted on chromosome 10 (PTEN) levels decreased in the high-salt
      treated rats. In addition, phosphorylated Akt (S473) and phosphorylation of the
      endothelial isoform of NO synthase (NOS3) at S1177 increased. Treatment with the
      TGF-beta receptor I/activin receptor-like kinase 5 inhibitor reduced Smad2
      phosphorylation to levels observed in rats on the low-salt diet and prevented the
      downstream signaling events induced by the high-salt diet. In human umbilical
      vein endothelial cells, reduction in PTEN levels increased phosphorylated Akt and
      NOS3. Treatment of macrovascular endothelial cells with TGF-beta1 increased
      phosphorylated NOS3 and the concentration of NO metabolites in the medium but had
      no effect on either of these variables in cells pretreated with small interfering
      RNA directed against PTEN. Thus, during high salt intake, an increase in TGF-beta
      directly promoted a reduction in endothelial PTEN levels, which in turn regulated
      Akt activation and NOS3 phosphorylation. This effect closes a feedback loop that
      potentially mitigates the effect of TGF-beta on the vasculature. 

PMID- 24041948
TI  - Atrial natriuretic peptide genetic variant rs5065 and risk for cardiovascular
      disease in the general community: a 9-year follow-up study.
AB  - We analyzed the phenotype associated with the atrial natriuretic peptide (ANP)
      genetic variant rs5065 in a random community-based sample. We also assessed and
      compared the biological action of 2 concentrations (10(-10) mol/L, 10(-8) mol/L)
      of ANP and ANP-RR, the protein variant encoded by the minor allele of rs5065, on
      activation of the guanylyl cyclase (GC)-A and GC-B receptors, production of the
      second messenger 3',5'-cGMP in endothelial cells, and endothelial permeability.
      rs5065 genotypes were determined in a cross-sectional adult cohort from Olmsted
      County, MN (n=1623). Genotype frequencies for rs5065 were 75%, 24%, and 1% for
      TT, TC, and CC, respectively. Multivariate analysis showed that the C allele was
      associated with increased risk of cerebrovascular accident (hazard ratio, 1.43;
      95% confidence interval, 1.09-1.86; P=0.009) and higher prevalence of myocardial
      infarction (odds ratio, 1.82; 95% confidence interval, 1.07-3.09; P=0.026). ANP
      RR 10(-8) mol/L activated the GC-A receptor (83.07+/-8.31 versus no treatment
      0.18+/-0.04 per 6 wells; P=0.006), whereas ANP-RR 10(-10) mol/L did not. Neither
      10(-8) mol/L nor 10(-10) mol/L ANP-RR activated GC-B receptor (P=0.10, P=0.35).
      ANP 10(-8) mol/L and ANP-RR 10(-8) mol/L stimulated 3',5'-cGMP production in
      endothelial cells similarly (P=0.58). Both concentrations of ANP-RR significantly
      enhanced human aortic endothelial cell permeability (69 versus 29 relative
      fluorescence units [RFUs], P=0.012; 58 versus 39 RFUs, P=0.015) compared with
      ANP. The minor allele of rs5065 was associated with increased cardiovascular
      risk. ANP-RR activated the GC-A receptor, increased 3',5'-cGMP in endothelial
      cells, and when compared with ANP, augmented endothelial cell permeability. 

PMID- 24041949
TI  - Calorie restriction attenuates cardiac remodeling and diastolic dysfunction in a
      rat model of metabolic syndrome.
AB  - Calorie restriction (CR) can modulate the features of obesity-related metabolic
      and cardiovascular diseases. We have recently characterized DahlS.Z
      Lepr(fa)/Lepr(fa) (DS/obese) rats, derived from a cross between Dahl salt
      sensitive and Zucker rats, as a new animal model of metabolic syndrome. DS/obese
      rats develop hypertension and manifest left ventricular remodeling and diastolic
      dysfunction, as well as increased cardiac oxidative stress and inflammation. We
      have now investigated the effects of CR on cardiac pathophysiology in DS/obese
      rats. DS/obese rats were fed either normal laboratory chow ad libitum or a
      calorie-restricted diet (65% of the average food intake for ad libitum) from 9 to
      13 weeks. Age-matched homozygous lean (DahlS.Z-Lepr(+)/Lepr(+) or DS/lean)
      littermates served as controls. CR reduced body weight in both DS/obese and
      DS/lean rats, as well as attenuated the development of hypertension in DS/obese
      rats without affecting blood pressure in DS/lean rats. CR also reduced body fat
      content, ameliorated left ventricular hypertrophy, fibrosis, and diastolic
      dysfunction, and attenuated cardiac oxidative stress and inflammation in DS/obese
      rats. In addition, it increased serum adiponectin concentration, as well as
      downregulated the expression of angiotensin-converting enzyme and angiotensin II
      type 1A receptor genes in the heart of DS/obese rats. Our results thus show that
      CR attenuated obesity and hypertension, as well as left ventricular remodeling
      and diastolic dysfunction in DS/obese rats, with these latter effects being
      associated with reduced cardiac oxidative stress and inflammation. 

PMID- 24041950
TI  - Glutamate receptors and presympathetic neuronal hyperactivity of the central
      nervous system in hypertension.

PMID- 24041952
TI  - White-coat hypertension: new insights from recent studies.

PMID- 24041951
TI  - Evaluating the Framingham hypertension risk prediction model in young adults: the
      Coronary Artery Risk Development in Young Adults (CARDIA) study.
AB  - A prediction model was developed in the Framingham Heart Study (FHS) to evaluate
      the short-term risk of hypertension. Our goal was to determine the predictive
      ability of the FHS hypertension model in a cohort of young adults advancing into
      middle age and compare it with the predictive ability of prehypertension and
      individual components of the FHS model. We studied 4388 participants, aged 18 to
      30 years without hypertension at baseline, enrolled in the Coronary Artery Risk
      Development in Young Adults (CARDIA) Study, who participated in 2 consecutive
      examinations occurring 5 years apart between the baseline (1985-1986) and year 25
      examination (2010-2011). Weibull regression was used to assess the association of
      the FHS model overall, individual components of the FHS model, and
      prehypertension with incident hypertension. During the 25-year follow-up period,
      1179 participants developed incident hypertension. The FHS hypertension model (c
      index=0.84; 95% confidence interval, 0.83-0.85) performed well in discriminating
      those who did and did not develop hypertension and was better than
      prehypertension alone (c-index=0.71; 95% confidence interval, 0.70-0.73). The
      predicted risk from the FHS hypertension model was systematically lower than the
      observed hypertension incidence initially (chi(2)=249.4; P<0.001) but
      demonstrated a good fit after recalibration (chi(2)=14.6; P=0.067). In summary,
      the FHS model performed better than prehypertension and may be a useful tool for
      identifying young adults with a high risk for developing hypertension. 

PMID- 24041953
TI  - Stimulatory effects of cardiotrophin 1 on atherosclerosis.
AB  - Cardiotrophin 1 (CT-1), an interleukin-6 family cytokine, was recently shown to
      be expressed in the intima of early atherosclerotic lesions in the human carotid
      artery. CT-1 stimulates proatherogenic molecule expression in human vascular
      endothelial cells and monocyte migration. However, it has not been reported
      whether CT-1 accelerates atherosclerosis. This study was performed to examine the
      stimulatory effects of CT-1 on human macrophage foam cell formation and vascular
      smooth muscle cell migration and proliferation in vitro, and on the development
      of atherosclerotic lesions in apolipoprotein E-deficient (ApoE(-/-)) mice in
      vivo. CT-1 was expressed at high levels in endothelial cells and macrophages in
      both humans and ApoE(-/-) mice. CT-1 significantly enhanced oxidized low-density
      lipoprotein-induced foam cell formation associated with increased levels of CD36
      and acyl-CoA:cholesterol acyltransferase-1 expression in human monocyte-derived
      macrophages. CT-1 significantly stimulated the migration, proliferation, and
      collagen-1 expression in human aortic vascular smooth muscle cells. Four-week
      infusion of CT-1 into ApoE(-/-) mice significantly accelerated the development of
      aortic atherosclerotic lesions with increased monocyte/macrophage infiltration,
      vascular smooth muscle cell proliferation, and collagen-1 content in the aortic
      wall. Activation of inflammasome, such as apoptosis-associated speck-like protein
      containing a caspase recruitment domain, nuclear factor kappaB, and
      cyclooxygenase-2, was observed in exudate peritoneal macrophages from ApoE(-/-)
      mice infused with CT-1. Infusion of anti-CT-1-neutralizing antibody alone into
      ApoE(-/-) mice significantly suppressed monocyte/macrophage infiltration in
      atherosclerotic lesions. These results indicate that CT-1 accelerates the
      development of atherosclerotic lesions by stimulating the inflammasome, foam cell
      formation associated with CD36 and acyl-CoA:cholesterol acyltransferase-1
      upregulation in macrophages, and migration, proliferation, and collagen-1
      production in vascular smooth muscle cells. 

PMID- 24041954
TI  - Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of
      angiotensin II type I receptor autoantibody-enhanced renal and blood pressure
      response during pregnancy.
AB  - Hypertension during preeclampsia is associated with increased maternal vascular
      sensitivity to angiotensin II (ANGII). This study was designed to determine
      mechanisms whereby agonistic autoantibodies to the ANGII type I receptor (AT1-AA)
      enhance blood pressure (mean arterial pressure [MAP]) and renal vascular
      sensitivity to ANGII during pregnancy. First, we examined MAP and renal artery
      resistance index in response to chronic administration of ANGII or AT1-AA or AT1
      AA+ANGII in pregnant rats compared with control pregnant rats. To examine
      mechanisms of heightened sensitivity in response to AT1-AA during pregnancy, we
      examined the role of endogenous ANGII in AT1-AA-infused pregnant rats, and that
      of endothelin-1 and oxidative stress in AT1-AA+ANGII-treated rats. Chronic ANGII
      increased MAP from 95+/-2 in normal pregnant rats to 115+/-2 mm Hg; chronic AT1
      AA increased MAP to 118+/-1 mm Hg in normal pregnant rats, which further
      increased to 123+/-2 mm Hg with AT1-AA+ANGII. Increasing ANGII from 10(-11) to
      10(-8) decreased afferent arteriole diameter from 15% to 20% but sharply
      decreased afferent arteriole diameter to 60% in AT1-AA-pretreated vessels. Renal
      artery resistance index increased from 0.67 in normal pregnant rats to 0.70 with
      AT1-AA infusion, which was exacerbated to 0.74 in AT1-AA+ANGII-infused rats. AT1
      AA-induced hypertension decreased with enalapril but was not attenuated. Both
      tissue endothelin-1 and reactive oxygen species increased with AT1-AA+ANGII
      compared with AT1-AA alone, and blockade of either of these pathways had
      significant effects on MAP or renal artery resistance index. These data support
      the hypothesis that AT1-AA, via activation of endothelin-1 and oxidative stress
      and interaction with endogenous ANGII, is an important mechanism whereby MAP and
      renal vascular responses are enhanced during preeclampsia. 

PMID- 24041955
TI  - High-dose-rate prostate brachytherapy based on registered transrectal ultrasound
      and in-room cone-beam CT images.
AB  - PURPOSE: To present a high-dose-rate (HDR) brachytherapy procedure for prostate
      cancer using transrectal ultrasound (TRUS) to contour the regions of interest and
      registered in-room cone-beam CT (CBCT) images for needle reconstruction. To
      characterize the registration uncertainties between the two imaging modalities
      and explore the possibility of performing the procedure solely on TRUS. METHODS
      AND MATERIALS: Patients were treated with a TRUS/CBCT-based HDR brachytherapy
      procedure. For 100 patients, dosimetric results were analyzed. For 40 patients,
      registration uncertainties were examined by determining differences in fiducial
      marker positions on TRUS and registered CBCT. The accuracy of needle
      reconstruction on TRUS was investigated by determining the position differences
      of needle tips on TRUS and CBCT. The dosimetric impact of reregistration and
      needle reconstruction on TRUS only was studied for 8 patients. RESULTS: The
      average prostate V100 was 97.8%, urethra D10 was 116.3%, and rectum D1 cc was
      66.4% of the prescribed dose. For 85% of the patients, registration inaccuracies
      were within 3 mm. Large differences were found between needle tips on TRUS and
      CBCT, especially in cranial-caudal direction, with a maximum of 10.4 mm.
      Reregistration resulted in a maximum V100 reduction of 0.9%, whereas needle
      reconstruction on TRUS only gave a maximum reduction of 9.4%. CONCLUSIONS: HDR
      prostate brachytherapy based on TRUS combined with CBCT is an accurate method.
      Registration uncertainties, and consequently dosimetric inaccuracies, are small
      compared with the uncertainties of performing the procedure solely based on
      static TRUS images. CBCT imaging is a requisite in our current procedure.

PMID- 24041957
TI  - Glaucocalyxin A, a negative Akt regulator, specifically induces apoptosis in
      human brain glioblastoma U87MG cells.
AB  - Akt is becoming an attractive target in the development of anti-tumor agents. In
      the present study, we aimed to discover novel negative Akt regulators against
      malignant glioma. An Akt regulator screening platform performed in an Akt-GFP
      overexpression cell line was developed, and natural product library was screened
      and evaluated using this platform. In addition, the cytotoxic effect of the
      regulator was detected by MTT assay. Cell apoptosis was assayed by Hoechst 33342
      staining and flow cytometry analysis. Afterwards, the apoptotic signaling pathway
      was investigated by western blot analysis. Glaucocalyxin A, isolated from
      Rabdosia japonica, was identified as a potent negative regulator of Akt. In human
      derived malignant glioma U87MG cells, glaucocalyxin A inhibited Akt
      phosphorylation, suppressed proliferation, and promoted apoptosis in a dose
      dependent manner, but not in normal glial cells. Furthermore, glaucocalyxin A
      activated caspase-3, decreased BAD phosphorylation, and reduced the expression of
      X-linked inhibitor of apoptosis protein. Taken together, these results indicated
      that glaucocalyxin A may become a promising candidate in the treatment of
      malignant glioma. 

PMID- 24041956
TI  - RTOG 95-17, a Phase II trial to evaluate brachytherapy as the sole method of
      radiation therapy for Stage I and II breast carcinoma--year-5 toxicity and
      cosmesis.
AB  - PURPOSE: Radiation Therapy Oncology Group (RTOG) 95-17, a Phase II trial to
      evaluate multicatheter brachytherapy (mCathBrachy) as the sole method of
      radiation therapy for Stage I-II breast cancer (BrCa), was the first cooperative
      group trial in North America to evaluate accelerated partial breast irradiation
      (APBI) and include patient-reported outcomes (PROs). This report presents the
      year-5 toxicity and cosmesis data. METHODS AND MATERIALS: After lumpectomy and
      axillary dissection for invasive BrCa (tumor size <3cm with zero to three
      positive lymph nodes), 100 patients (pts), 98 evaluable, were treated (txed) with
      mCathBrachy from 1997 to 2000 with 34Gy administered twice daily in 10 high-dose
      rate fractions or 45Gy in 3.5-6 days as a low-dose-rate implant to 1-2cm beyond
      the lumpectomy bed. The PROs and physician-reported outcomes of toxicity,
      cosmesis, and tx satisfaction at year-5 are reported here, defined as data
      submitted 54-78 months after tx. RESULTS: Grade (G) 1-2 skin toxicity developed
      in 78% of the pts and G3 in 13% (no G4). The tx effects included skin
      dimpling/indentation (37%), fibrosis (45%), telangiectasias (45%), skin catheter
      marks (54%), and symptomatic fat necrosis (15%). Breast asymmetry was reported in
      73%. Rates of excellent-to-good cosmesis were similar between PROs (66%) and
      radiation oncologists (68%). The PROs of tx satisfaction at year-5 was 75%.
      CONCLUSIONS: RTOG 95-17 documents the year-5 skin toxicity and tx effects of
      mCathBrachy APBI, which are associated with PROs of good-to-excellent cosmesis
      and high tx satisfaction. This emphasizes the importance of PROs when assessing
      BrCa tx. National Surgical Adjuvant Breast and Bowel Project B39/RTOG 0413 will
      allow for definitive comparisons between APBI and whole breast radiation therapy.

PMID- 24041958
TI  - Decipher the mechanisms of rabbit's low susceptibility to prion infection.
AB  - Rabbits have low susceptibility to prion infection. Studies on prion protein
      (PrP) from animal species of different susceptibility to prion diseases
      identified key amino acid residues, specific motif, and special features in
      rabbit prion protein (RaPrP(C)) that contribute to the stability of rabbit PrP(C)
      and low susceptibility to prion infection. However, there is no evidence showing
      that rabbits are completely resistant to prion diseases. It has been reported
      that the rabbit prion could be generated in vitro through protein misfolding
      cyclic amplification and proved to be infectious and transmissible. Here, we
      reviewed studies on rabbit-specific PrP structures and features in relation to
      rabbit's low susceptibility to prion infection. 

PMID- 24041959
TI  - Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine
      kinase.
AB  - The non-receptor-type tyrosine kinase c-Abl is involved in actin dynamics in the
      cytoplasm. Having three nuclear localization signals (NLSs) and one nuclear
      export signal, c-Abl shuttles between the nucleus and the cytoplasm. Although
      monomeric actin and filamentous actin (F-actin) are present in the nucleus,
      little is known about the relationship between c-Abl and nuclear actin dynamics.
      Here, we show that nuclear-localized c-Abl induces nuclear F-actin formation.
      Adriamycin-induced DNA damage together with leptomycin B treatment accumulates c
      Abl into the nucleus and increases the levels of nuclear F-actin. Treatment of c
      Abl-knockdown cells with Adriamycin and leptomycin B barely increases the nuclear
      F-actin levels. Expression of nuclear-targeted c-Abl (NLS-c-Abl) increases the
      levels of nuclear F-actin even without Adriamycin, and the increased levels of
      nuclear F-actin are not inhibited by inactivation of Abl kinase activity.
      Intriguingly, expression of NLS-c-Abl induces the formation of long and winding
      bundles of F-actin within the nucleus in a c-Abl kinase activity-dependent
      manner. Furthermore, NLS-c-AblDeltaC, which lacks the actin-binding domain but
      has the full tyrosine kinase activity, is incapable of forming nuclear F-actin
      and in particular long and winding nuclear F-actin bundles. These results suggest
      that nuclear c-Abl plays critical roles in actin dynamics within the nucleus. 

PMID- 24041960
TI  - High glucose increases glomerular filtration barrier permeability by activating
      protein kinase G type Ialpha subunits in a Nox4-dependent manner.
AB  - Hyperglycemia is a primary factor that disturbs podocyte function in the
      glomerular filtration process; this disturbance leads to the development of
      diabetic nephropathy, and ultimately, renal failure. Podocyte function may also
      be altered by biological agents that modify protein kinase activity, including
      the cGMP-activated protein kinase type Ialpha (PKGIalpha). We hypothesized that
      hyperglycemia-induced podocyte protein hyperpermeability was dependent on
      PKGIalpha activation, and that PKGIalpha was activated via dimerization induced
      by reactive oxygen species. This hypothesis was investigated in rat podocytes
      cultured in high glucose (HG, 30 mM). Protein expression was measured with
      Western blot and immunofluorescence. Podocyte permeability was measured with a
      transmembrane albumin flux assay. We found that HG increased podocyte
      permeability in long-term incubations (1, 3, and 5 days); permeability was
      increased by 66% on day 5. This effect was abolished with apocynin, a NAD(P)H
      inhibitor, and Rp-8-Br-cGMPS, a PKG inhibitor. It was also abolished by
      introducing small interfering RNAs (siRNAs) against Nox4 and PKGIalpha into
      cultured podocytes. Furthermore, HG increased PKGIalpha dimerization by 138%
      (0.23 +/- 0.04 vs. 0.54 +/- 0.09; P<0.05); this effect was abolished with a siRNA
      against Nox4. Our observations suggested that HG could increase albumin
      permeability across the podocyte filtration barrier via Nox4-dependent PKGIalpha
      dimerization.

PMID- 24041962
TI  - Schwann cell autophagy counteracts the onset and chronification of neuropathic
      pain.
AB  - Axonal degeneration in peripheral nerves after injury is accompanied by myelin
      degradation initiated by Schwann cells (SCs). These cells activate autophagy, a
      ubiquitous cytoprotective process essential for degradation and recycling of
      cellular constituents. Concomitantly to nerve insult and axonal degeneration,
      neuropathic pain (NeP) arises. The role of SC autophagy in the mechanisms
      underlying NeP is still unknown. In this study, we examined the role of the
      autophagy during the early phase of Wallerian degeneration in NeP induction and
      chronification by using a murine model of peripheral nerve lesion (chronic
      constriction injury). We demonstrate that the autophagy inducer rapamycin,
      administered in the first week after nerve damage, induces long-lasting analgesic
      and antiinflammatory effects, facilitates nerve regeneration, and prevents pain
      chronification. Conversely, when autophagy is altered, by means of autophagic
      inhibitor 3-methyladenine administration or as occurs in activating molecule in
      Beclin-1-regulated autophagy transgenic mice (Ambra1(+/gt)), NeP is dramatically
      enhanced and prolonged. Immunohistochemical and ultrastructural evaluations show
      that rapamycin is able to increase autophagic flux in SCs, to accelerate myelin
      compaction, and to reduce inflammatory and immune reaction. Proteomic analysis
      combined with bioinformatic analysis suggests that a redox-sensitive mechanism
      could be responsible for SC autophagy activation. These data suggest that a
      deficiency of autophagic activity in SCs can be an early event in the origin of
      NeP chronification and that autophagy modulation may represent a powerful
      pharmacological approach to prevent the onset and chronification of NeP in the
      clinical setting. 

PMID- 24041961
TI  - Roles of glutamate, substance P, and gastrin-releasing peptide as spinal
      neurotransmitters of histaminergic and nonhistaminergic itch.
AB  - We investigated roles for substance P (SP), gastrin-releasing peptide (GRP), and
      glutamate in the spinal neurotransmission of histamine-dependent and -independent
      itch. In anesthetized mice, responses of single superficial dorsal horn neurons
      to intradermal (i.d.) injection of chloroquine were partially reduced by spinal
      application of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate acid
      (AMPA)/kainate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Co
      application of CNQX plus a neurokinin-1 (NK-1) antagonist produced stronger
      inhibition, while co-application of CNQX, NK-1, and GRP receptor (GRPR)
      antagonists completely inhibited firing. Nociceptive-specific and wide dynamic
      range-type neurons exhibited differential suppression by CNQX plus either the
      GRPR or NK-1 antagonist, respectively. Neuronal responses elicited by i.d.
      histamine were abolished by CNQX alone. In behavioral studies, individual
      intrathecal administration of a GRPR, NK-1, or AMPA antagonist each significantly
      attenuated chloroquine-evoked scratching behavior. Co-administration of the NK-1
      and AMPA antagonists was more effective, and administration of all 3 antagonists
      abolished scratching. Intrathecal CNQX alone prevented histamine-evoked
      scratching behavior. We additionally employed a double-label strategy to
      investigate molecular markers of pruritogen-sensitive dorsal root ganglion (DRG)
      cells. DRG cells responsive to histamine and/or chloroquine, identified by
      calcium imaging, were then processed for co-expression of SP, GRP, or vesicular
      glutamate transporter type 2 (VGLUT2) immunofluorescence. Subpopulations of
      chloroquine- and/or histamine-sensitive DRG cells were immunopositive for SP
      and/or GRP, with >80% immunopositive for VGLUT2. These results indicate that SP,
      GRP, and glutamate each partially contribute to histamine-independent itch.
      Histamine-evoked itch is mediated primarily by glutamate, with GRP playing a
      lesser role. Co-application of NK-1, GRP, and AMPA receptor antagonists may prove
      beneficial in treating chronic itch. 

PMID- 24041963
TI  - Use of conivaptan for management of hyponatremia following surgery for Cushing's
      disease.
AB  - BACKGROUND: Hyponatremia due to syndrome of inappropriate antidiuretic hormone
      secretion (SIADH) is a common osmoregulatory complication following surgery for
      Cushing's disease. Conventional management includes water restriction and sodium
      repletion, however this regimen does not address the underlying pathophysiology
      of excessive vasopressin production. Vaptans are arginine vasopressin receptor
      antagonists shown to be effective in correcting water excess in other disease
      states of euvolemic and hypervolemic hyponatremia. The use of these agents has
      not been reported in Cushing's patients. METHODS: We retrospectively studied
      Cushing's patients at our institution with post-surgical hyponatremia
      (Na<130mEq/L) treated with and without conivaptan between 2005 and 2011. We
      report rates of serum sodium normalization and compare length-of-stay (LOS)
      between the groups. RESULTS: Hyponatremia developed in six of 98 patients (6.1%)
      undergoing resection of ACTH-positive pituitary adenomas. Three patients received
      conivaptan and fluid restriction+/-sodium supplementation, and three received
      conventional therapy alone. The rate of serum sodium normalization with
      conivaptan was 5.8+/-2.3mEq/L/20mg IV bolus given every 24h. All patients
      receiving conivaptan were discharged with normal serum sodium values and no
      instances of rapid overcorrection occurred. A trend toward longer LOS occurred in
      patients treated with conivaptan (4.6+/-0.3 days, mean+/-SE) versus conventional
      therapy alone (1.6+/-0.3 days). CONCLUSIONS: Conivaptan is a potentially useful
      treatment option for hyponatremia in the setting of Cushing's disease patients
      after pituitary surgery.

PMID- 24041964
TI  - Neuroendoscopic options in the treatment of mesencephalic expanding cysts: report
      of four cases and review of the literature.
AB  - OBJECTIVE: Mesencephalic expanding cysts, also called lacunae, are rare
      intraparenchymal, multilobulated cavities of variable diameter mostly localized
      in the thalamo-mesencephalic region. In symptomatic cases, usually presenting
      with hydrocephalus or midbrain syndrome, surgical treatment is required and,
      considering their position, a minimally invasive approach should be preferred.
      METHODS: Four cases of expanding mesencephalic cysts endoscopically treated in
      three different Italian centers are described. Other possible causes of
      intracerebral cyst were excluded in all cases by complete neuroimaging and
      laboratory screening. All patients presented with signs and symptoms of midbrain
      compression and a slight to moderate ventricular dilation was present in three
      cases. RESULTS: All patients underwent endoscopic cyst fenestration into the
      ventricle, associated with endoscopic third-ventriculostomy (ETV) in two cases
      and with cyst wall biopsy in one case. One patient suffered from transient
      worsening of her hemiparesis due to intraoperative bleeding. All patients showed
      clinical improvement and a reduction in cyst size on follow-up magnetic resonance
      images (MRI). CONCLUSION: Neuroendoscopy appears to be an effective, probably
      definitive surgical option in the treatment of symptomatic mesencephalic
      expanding cysts. Associating ETV with cyst fenestration seems to offer more
      complete treatment. Deep intracystic navigation and cyst wall biopsy should be
      avoided.

PMID- 24041965
TI  - Deep brain stimulation of the subthalamic nucleus in Parkinson's disease:
      surgical technique, tips, tricks and complications.
AB  - Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become a
      frequently performed surgery in patients with advanced Parkinson's disease. The
      technique has been further refined throughout the years by improved imaging
      techniques, advanced neurophysiological recording possibilities, and advances in
      hardware and software technology. In addition, the complications, which can be
      divided into surgery-related, target-related, and hardware-related complications,
      were better recognised and managed. In this review, we describe our experience
      specifically with the surgery of STN DBS in the light of the existing literature.
      Tips and tricks, complications and their management are the main elements of this
      article. In addition, we provide scientific information from our research and
      other groups in specific sections. 

PMID- 24041966
TI  - Inhibition of complement component C5 protects porcine chondrocytes from
      xenogeneic rejection.
AB  - OBJECTIVE: Tissue-based xenografts such as cartilage are rejected within weeks by
      humoral and cellular mechanisms that preclude its clinical application in
      regenerative medicine. The problem could be overcome by identifying key molecules
      triggering rejection and the development of genetic-engineering strategies to
      counteract them. Accordingly, high expression of alpha1,2-fucosyltransferase (HT)
      in xenogeneic cartilage reduces the galactose alpha1,3-galactose (Gal) antigen
      and delays rejection. Yet, the role of complement activation in this setting is
      unknown. DESIGN: To determine its contribution, we assessed the effect of
      inhibiting C5 complement component in alpha1,3-galactosyltransferase-knockout
      (Gal KO) mice transplanted with porcine cartilage and studied the effect of human
      complement on porcine articular chondrocytes (PAC). RESULTS: Treatment with an
      anti-mouse C5 blocking antibody for 5 weeks enhanced graft survival by reducing
      cellular rejection. Moreover, PAC were highly resistant to complement-mediated
      lysis and primarily responded to human complement by releasing IL-6 and IL-8.
      This occurred even in the absence of anti-Gal antibody and was mediated by both
      C5a and C5b-9. Indeed, C5a directly triggered IL-6 and IL-8 secretion and up
      regulated expression of swine leukocyte antigen I (SLA-I) and adhesion molecules
      on chondrocytes, all processes that enhance cellular rejection. Finally, the use
      of anti-human C5/C5a antibodies and/or recombinant expression of human complement
      regulatory molecule CD59 (hCD59) conferred protection in correspondence with
      their specific functions. CONCLUSIONS: Our study demonstrates that complement
      activation contributes to rejection of xenogeneic cartilage and provides valuable
      information for selecting approaches for complement inhibition.

PMID- 24041967
TI  - Sequencing analysis of the spinal bulbar muscular atrophy CAG expansion reveals
      absence of repeat interruptions.
AB  - Trinucleotide repeat disorders are a heterogeneous group of diseases caused by
      the expansion, beyond a pathogenic threshold, of unstable DNA tracts in different
      genes. Sequence interruptions in the repeats have been described in the majority
      of these disorders and may influence disease phenotype and heritability. Spinal
      bulbar muscular atrophy (SBMA) is a motor neuron disease caused by a CAG
      trinucleotide expansion in the androgen receptor (AR) gene. Diagnostic testing
      and previous research have relied on fragment analysis polymerase chain reaction
      to determine the AR CAG repeat size, and have therefore not been able to assess
      the presence of interruptions. We here report a sequencing study of the AR CAG
      repeat in a cohort of SBMA patients and control subjects in the United Kingdom.
      We found no repeat interruptions to be present, and we describe differences
      between sequencing and traditional sizing methods. 

PMID- 24041968
TI  - Cheek cell-derived alpha-synuclein and DJ-1 do not differentiate Parkinson's
      disease from control.
AB  - Recently, alpha-synuclein (alpha-syn) and DJ-1, 2 proteins critically involved in
      Parkinson's disease (PD), have been shown to be present in saliva, suggesting
      their potential utility as biomarkers of PD. However, the origin and influence of
      demographic characteristics (e.g., age or sex) on these proteins are unknown. We
      identified cheek epithelium, which forms the majority of the cellular component
      of saliva and is readily accessible clinically, as 1 of several potential sources
      of salivary alpha-syn and DJ-1. However, no PD-related trend in the cellular
      component was present. In the supernatant collected from 198 healthy subjects, no
      correlation was seen between salivary DJ-1 or alpha-syn with age. When male and
      female subjects were analyzed separately, a weak age-dependent increase in DJ-1
      level was present in male subjects, along with slightly increased alpha-syn in
      female subjects. These results, albeit largely negative, provide critical
      information for understanding the salivary gland pathology and saliva as a PD
      biomarker source, and must be considered in future investigations of salivary
      changes in PD. 

PMID- 24041969
TI  - Assessing the role of the TREM2 p.R47H variant as a risk factor for Alzheimer's
      disease and frontotemporal dementia.
AB  - A non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene
      has recently been reported to be a strong genetic risk factor for Alzheimer's
      disease (AD). Also, rare recessive mutations have been associated with
      frontotemporal dementia (FTD). We aimed to investigate the role of p.R47H variant
      in AD and FTD through a multi-center study comprising 3172 AD and 682 FTD
      patients and 2169 healthy controls from Spain. We found that 0.6% of AD patients
      carried this variant compared to 0.1% of controls (odds ratio [OR] = 4.12, 95%
      confidence interval [CI] = 1.21-14.00, p = 0.014). A meta-analysis comprising
      32,598 subjects from 4 previous studies demonstrated the large effect of the
      p.R47H variant in AD risk (OR = 4.11, 95% CI = 2.99-5.68, p = 5.27*10(-18)). We
      did not find an association between p.R47H and age of onset of AD or family
      history of dementia. Finally, none of the FTD patients harbored this genetic
      variant. These data strongly support the important role of p.R47H in AD risk, and
      suggest that this rare genetic variant is not related to FTD.

PMID- 24041971
TI  - Uncoupling protein 2 deficiency aggravates astrocytic endoplasmic reticulum
      stress and nod-like receptor protein 3 inflammasome activation.
AB  - Astrocytes play crucial roles in determining the susceptibility to oxidative
      stress in the brain, and uncoupling protein 2 (UCP2) has been demonstrated to
      regulate reactive oxygen species (ROS) production. However, it is unclear whether
      UCP2 is expressed in astrocytes, and whether it participates in the regulation of
      astrocytic functions. Here we show that UCP2 knockout exacerbated dopaminergic
      neuron loss in a murine model of 1,2,3,6-methyl-phenyl-tetrahydropyridine (MPTP)
      induced Parkinson's disease (PD), accompanied by overactivation of astrocytes. We
      further detected expression of UCP2 in primary cultures of mesencephalic
      astrocytes. UCP2 knockout increased intracellular ROS production and induced
      oxidative stress in response to l-methyl-4-phenylpyridinium (MPP(+)) treatment.
      Subsequently, UCP2 deficiency exacerbated endoplasmic reticulum (ER) stress, as
      evidenced by the upregulations of C/EBP homologous protein (CHOP), cleavage of
      caspase-12, and aggravated neuroinflammation via the activation of nod-like
      receptor protein 3 (NLRP3) inflammasomes in astrocytes. Collectively, our study
      indicates that UCP2 expressed in astrocytes modulates ER stress and
      neuroinflammation, and is crucial for the survival of dopaminergic neuron in the
      pathogenesis of PD. These findings gives us insights into the potential of UCP2
      as a novel therapeutic avenue for PD treatment. 

PMID- 24041970
TI  - Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease.
AB  - Abberant lipid metabolism is implicated in Alzheimer's disease (AD)
      pathophysiology, but the connections between AD and lipid metabolic pathways are
      not fully understood. To investigate plasma lipids in AD, a multiplatform screen
      (n = 35 by liquid chromatography-mass spectrometry and n = 35 by nuclear magnetic
      resonance) was developed, which enabled the comprehensive analysis of plasma from
      3 groups (individuals with AD, individuals with mild cognitive impairment (MCI),
      and age-matched controls). This screen identified 3 phosphatidylcholine (PC)
      molecules that were significantly diminished in AD cases. In a subsequent
      validation study (n = 141), PC variation in a bigger sample set was investigated,
      and the same 3 PCs were found to be significantly lower in AD patients: PC
      16:0/20:5 (p < 0.001), 16:0/22:6 (p < 0.05), and 18:0/22:6 (p < 0.01). A receiver
      operating characteristic (ROC) analysis of the PCs, combined with apolipoprotein
      E (ApoE) data, produced an area under the curve predictive value of 0.828.
      Confirmatory investigations into the background biochemistry indiciated no
      significant change in plasma levels of 3 additional PCs of similar structure,
      total choline containing compounds or total plasma omega fatty acids, adding to
      the evidence that specific PCs play a role in AD pathology.

PMID- 24041972
TI  - Microtubule-associated protein tau genetic variations are uncommon cause of
      frontotemporal dementia in south India.
AB  - Microtubule-associated protein tau (MAPT) positive neuropathology is the
      characteristic feature of majority of frontotemporal dementia (FTD) cases, which
      is due to the mutations or haplotypic variations in the gene encoding MAPT
      (MAPT). The present study was aimed at determining the frequency of genetic
      variations in MAPT in a south Indian FTD cohort. The frequency of mutations were
      determined in 116 FTD, 8 progressive supranuclear palsy (PSP) and 3 corticobasal
      syndrome (CBS) patients and haplotype diversity were analyzed in a study cohort
      comprising 116 FTD, 8 PSP, 3 CBS, 194 other dementia groups, 78 mild cognitive
      impairment (MCI) and 130 cognitively normal individuals and report no pathogenic
      mutations in FTD/PSP/CBS or haplotypic association with disease risk in FTD or
      other dementia patients. These findings suggest that there may be other genetic
      or epigenetic factors contributing to the pathogenesis of FTD in the south Indian
      population. 

PMID- 24041973
TI  - [Mixed papilloma: a case report].

PMID- 24041974
TI  - [Flexible endoscope in thoracic surgery: CITES or cVATS?].
AB  - Early pain and persistent parietal disorders remains a major unresolved problem
      in thoracic surgery. Thoracotomy and the use of multiple ports in most Video
      Assisted Thoracic Surgery (VATS) procedures are the major cause of this
      persistent pain. For the last decade, a few publications describing the use of
      either single incision VATS and cervical thoracic approaches have been reported
      without significant results in comparison with current used techniques.
      Intercostals compression during surgery and early after by intercostals chest
      tube placement, are probably the major cause of postoperative pain. Flexible
      endoscope is currently used in several surgeries and will take more and more
      importance in our daily use in thoracic surgery. Instrument flexibility allows
      its use through minimally invasive approaches and offers a very interesting intra
      thoracic navigation. We describe here the first use in France of a flexible
      endoscope in thoracic surgery through a single cervical incision to perform
      simultaneous exploration and biopsies of the mediastinum and right pleura using
      the original approach of Cervical Incision Thoracic Endoscopic Surgery (CITES). 

PMID- 24041975
TI  - [Rare complication of a post-traumatic left diaphragmatic hernia].
AB  - Diaphragmatic hernia is a post-traumatic lesion specific trauma that may go
      unnoticed. The left hemidiaphragm is the most frequently affected. The diagnosis
      is then made at the occasion of a complication, especially gastric volvulus. The
      authors report the case of a young man aged 26 years old with a gastric volvulus
      on post-traumatic diaphragmatic hernia diagnosed by CT. 

PMID- 24041976
TI  - Life-style and self-rated global health in Sweden: a prospective analysis
      spanning three decades.
AB  - OBJECTIVE: To study the relations between lifestyle factors (smoking, drinking,
      exercise, vegetable consumption, social relations) and global self-rated health
      in the adult Swedish population. METHOD: The data come from the Swedish Level of
      Living Survey, a face-to-face panel study. The analysis follows the respondents
      with good health in 1991 (N=4035) and uses multivariate logistic regression to
      assess the relations between lifestyle factors in 1991 and health in 2000 and
      2010. RESULTS: Baseline (1991) exercise, social support, smoking and vegetable
      consumption are associated with health in 2000 and/or 2010. 2000: Weekly exercise
      in 1991 increases the probability of good health by 6 percentage points [95% CI:
      1-10] compared to no exercise, and smoking 10 or more cigarettes a day decreases
      the probability of good health by 5 percentage points [95% CI 1-8]. Lacking
      social support decreases the probability of good health by 17 percentage points
      (95% CI: 9-25). 2010: Smoking 10 or more cigarettes a day decreases the
      probability of good health by 10 percentage points [95% CI 5-15], and eating
      vegetables every day increases the probability of good health by 4 percentage
      points [95% CI 0.2-7]. CONCLUSIONS: Exercise, smoking, social support and
      vegetable consumption are related to self-rated health 2000 and/or 2010.

PMID- 24041977
TI  - Development and validation of a technoeconomic analysis tool for early-stage
      evaluation of bio-based chemical production processes.
AB  - By using cost correlations and standard scale-factors, a spreadsheet-based early
      stage cost estimation tool was developed. Named BioPET (Biorenewables Process
      Evaluation Tool), this tool allows users to specify up to seven primary unit
      operations--fermentation, separation, three catalytic stages, and purification-
      along with key parameters for each. BioPET then computes an estimated minimum
      selling price for the pathway. Model validation was conducted by selecting three
      molecules (ethanol, succinic acid, and adipic acid), and comparing BioPET's
      results to literature values and to results from a commercial process design
      tool. BioPET produced virtually identical prices to the process design tool,
      although the costs were not identically distributed amongst the categories.
      BioPET produced estimates that were within 40% of other literature values at low
      feedstock costs, and within 5% at high feedstock costs.

PMID- 24041979
TI  - The impact of coastal defence structures (tetrapods) on decapod crustaceans in
      the southern North Sea.
AB  - Although the use of coastal defence structures is expected to increase, little is
      known about the ecological impact of such structures on the natural environment.
      In particular, the temporal and spatial patterns of communities in association
      with artificial substrate are still poorly understood. This study examined
      possible effects of experimental tetrapod fields on the decapod crustacean
      community in a subtidal hard-bottom area in the southern North Sea. We performed
      in situ studies in the fields and along transects oriented away from the tetrapod
      fields. Species composition and abundances were assessed before and after the
      introduction of the artificial material. The study revealed a significant
      decrease of smaller, less vagile species (Pisidia longicornis, Pilumnus
      hirtellus, Galathea squamifera) over the entire study area in the years following
      the tetrapod introduction. For 2 species, Hyas araneus and Homarus gammarus, the
      tetrapods appeared to be highly attractive as habitat and shelter because their
      abundance increased over time. No distinct spatial or temporal effects were
      observed for mobile predatory crabs, such as Cancer pagurus and Liocarcinus spp.
      The results of the study demonstrate that possible effects of artificial
      structures on macro-invertebrates in temperate hard-bottom areas are highly
      species-specific and depend on the size, lifestyle and ecological requirements of
      the species. This work highlights the importance of long-term studies. Our
      findings clearly indicate that more time is needed to distinguish between natural
      and anthropogenic influences on species distributions. 

PMID- 24041978
TI  - Sex hormone levels and risk of breast cancer with estrogen plus progestin.
AB  - BACKGROUND: Although high endogenous sex hormone levels and estrogen plus
      progestin (E+P) therapy are associated with increased breast cancer risk, it is
      unknown whether pretreatment levels of sex hormones modify E+P effect on breast
      cancer. METHODS: We conducted a nested case-control study within the Women's
      Health Initiative randomized clinical trial of E+P. The trial enrolled 16608
      postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer
      history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case
      subjects were identified and matched with 348 control subjects. Case and control
      subjects had their sex hormone levels measured at baseline (estrogens,
      testosterone, progesterone, and sex hormone-binding globulin [SHBG]) and year 1
      (estrogens and SHBG) using sensitive assays. All statistical tests were two
      sided. RESULTS: Statistically significant elevations in breast cancer risk were
      seen with greater pretreatment levels of total estradiol (P trend = .04),
      bioavailable estradiol (P trend = .03), estrone (P trend = .007), and estrone
      sulfate (P trend = .007). E+P increased all measured estrogens and SHGB at year 1
      (all P < .001). The effect of E+P on breast cancer risk was strongest in women
      whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone
      were in the lowest quartiles. For example, the odds ratio for E+P relative to
      placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest
      total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the
      highest total estradiol quartile; P interaction = .04). CONCLUSIONS: Women with
      lower pr-treatment endogenous estrogen levels were at greater risk of breast
      cancer during E+P therapy compared with those with higher levels. Further studies
      are warranted to confirm these findings.

PMID- 24041980
TI  - Lung procurement from a donor with a long-term left ventricular assist device.

PMID- 24041981
TI  - Bortezomib rescue therapy in a patient with recurrent antibody-mediated rejection
      after lung transplantation.

PMID- 24041982
TI  - Teaching ophthalmoscopy to medical students (the TOTeMS study).
AB  - PURPOSE: To determine medical student preferences for learning the ocular fundus
      examination and to assess their accuracy using different examination modalities.
      DESIGN: Prospective, randomized study of medical student education approaches.
      METHODS: First-year medical students received training in direct ophthalmoscopy
      using simulators and human volunteers. Students were randomized to receive vs not
      receive specific training on interpreting fundus photographs prior to accuracy
      assessments. Students' preferences for each of the 3 methods (direct
      ophthalmoscopy on simulators or human volunteers, or use of fundus photographs)
      and recognition of normal and abnormal fundus features were assessed. RESULTS: Of
      138 first-year medical students, 119 (86%) completed all required elements. For
      learning ophthalmoscopy, 85 (71%) preferred humans to simulators. For learning
      relevant features of the ocular fundus, 92 (77%) preferred photographs to
      ophthalmoscopy on simulators or humans. Accuracy of answers was better when
      interpreting fundus photographs than when performing ophthalmoscopy on simulators
      (P < .001). Performance improved after specific teaching about assessing fundus
      photographs before testing (P = .02). Examination of the ocular fundus was found
      easier and less frustrating when using photographs than when using ophthalmoscopy
      on simulators or humans. Eighty-four students (70%) said they would prefer to
      have fundus photographs instead of using the ophthalmoscope during upcoming
      clinical rotations. CONCLUSIONS: Students preferred fundus photographs for both
      learning and examining the ocular fundus. Identification of ocular fundus
      features was more accurate on photographs compared to examination by direct
      ophthalmoscopy. In the future, the increasing availability of nonmydriatic ocular
      fundus photography may allow replacement of direct ophthalmoscopy in many
      clinical settings for non-ophthalmologists.

PMID- 24041983
TI  - Disturbed heart rate variability: a dose-dependent response to elevated nitric
      oxide and carbon monoxide in exhaled breath.

PMID- 24041984
TI  - PFO closure vs. medical therapy in cryptogenic stroke or transient ischemic
      attack: a systematic review and meta-analysis.
AB  - BACKGROUND/OBJECTIVES: This study aims to assess whether patent foramen ovale
      (PFO) closure is superior to medical therapy in preventing recurrence of
      cryptogenic ischemic stroke or transient ischemic attack (TIA). METHODS: We
      searched PubMed for randomized trials which compared PFO closure with medical
      therapy in cryptogenic stroke/TIA using the items: "stroke or cerebrovascular
      accident or TIA" and "patent foramen ovale or paradoxical embolism" and "trial or
      study". RESULTS: Among 650 potentially eligible articles, 3 were included
      including 2303 patients. There was no statistically significant difference
      between PFO-closure and medical therapy in ischemic stroke recurrence (1.91% vs.
      2.94% respectively, OR: 0.64, 95%CI: 0.37-1.10), TIA (2.08% vs. 2.42%
      respectively, OR: 0.87, 95%CI: 0.50-1.51) and death (0.60% vs. 0.86%
      respectively, OR: 0.71, 95%CI: 0.28-1.82). In subgroup analysis, there was
      significant reduction of ischemic strokes in the AMPLATZER PFO Occluder arm vs.
      medical therapy (1.4% vs. 3.04% respectively, OR: 0.46, 95%CI: 0.21-0.98,
      relative-risk-reduction: 53.2%, absolute-risk-reduction: 1.6%, number-needed-to
      treat: 61.8) but not in the STARFlex device (2.7% vs. 2.8% with medical therapy,
      OR: 0.93, 95%CI: 0.45-2.11). Compared to medical therapy, the number of patients
      with new-onset atrial fibrillation (AF) was similar in the AMPLATZER PFO Occluder
      arm (0.72% vs. 1.28% respectively, OR: 1.81, 95%CI: 0.60-5.42) but higher in the
      STARFlex device (0.64% vs. 5.14% respectively, OR: 8.30, 95%CI: 2.47-27.84).
      CONCLUSIONS: This meta-analysis does not support PFO closure for secondary
      prevention with unselected devices in cryptogenic stroke/TIA. In subgroup
      analysis, selected closure devices may be superior to medical therapy without
      increasing the risk of new-onset AF, however. This observation should be
      confirmed in further trials using inclusion criteria for patients with high
      likelihood of PFO-related stroke recurrence.

PMID- 24041985
TI  - Short-term episodes of hypoxia induce posthypoxic hyperexcitability and selective
      death of GABAergic hippocampal neurons.
AB  - We have previously developed a rat hippocampal neuronal cell model for the
      registration of the preconditioning effect and posthypoxic hyperexcitability
      (Turovskaya et al., 2011). Repeated episodes of short-term hypoxia are reported
      to suppress the amplitude of Ca(2+) response to NMDA in majority of neurons,
      reflecting the effect of preconditioning in the culture. In addition, exposure to
      hypoxia causes posthypoxic hyperexcitability: this is characterized by the onset
      of spontaneous synchronous Ca(2+) transients in a population of neurons in a
      neural network during the period of reoxygenation after each hypoxic episode. The
      nature of this phenomenon is unknown, although it has been observed that there
      always exists a minority of neurons in which there is no effect of hypoxic
      preconditioning. In this small population of neurons, the amplitude of Ca(2+)
      response to NMDA is not suppressed, but rather increases after each episode of
      hypoxia. Here we report the type of these neurons and their role in the
      generation of posthypoxic hyperexcitability. We compared the effect of short-term
      hypoxia on the amplitude of the Ca(2+) response to NMDA and the Ca(2+) transient
      generation in two populations of neurons - inhibitory GABAergic and excitatory
      glutamatergic. We have demonstrated that the neurons in which the preconditioning
      effect was not observed are GABAergic. Moreover at the instant moment of the
      posthypoxic synchronous Ca(2+)-transient generation (during reoxygenation) there
      is a global increase of [Ca(2+)]i and subsequent apoptosis in some GABAergic
      neurons. Anti-inflammatory cytokine interleukin-10 prevents the development of
      posthypoxic hyperexcitability, inhibiting the spontaneous synchronous Ca(2+)
      transients. At the same time, interleukin-10 protects GABAergic neurons from
      death, by restoring the effect of hypoxic preconditioning in them. Activation of
      one of the signaling pathways initiated by interleukin-10 appears to be necessary
      for the development of hypoxic preconditioning in GABAergic neurons. Overall our
      results indicate that short-term episodes of hypoxia can damage GABAergic neurons
      and weaken the inhibitory action of GABAergic neurons in a neural network.
      Activation of PI3K-dependent survival signaling pathways in neurons of this type
      is a possible strategy to protect these cells against hypoxia. 

PMID- 24041986
TI  - Metabolic profiling of the mouse retina using amino acid signatures: insight into
      developmental cell dispersion patterns.
AB  - Pattern recognition has been used for the complete and statistically rigid
      classification of retinal neurons in vertebrates such as the adult cat, primate,
      rat and goldfish. Here, we label the mouse retina with antibodies against seven
      amino acids and use pattern recognition to characterize distinct retinal
      neurochemical cell classes based on their unique amino acid signatures. We
      followed the development of the cell classes in the X-inactivation transgenic
      mouse expressing the lacZ reporter gene on one X-chromosome. This mouse allows
      clonally related cells to be identified through differential beta-galactosidase
      activity due to random X-chromosome inactivation. Pattern recognition analysis
      partitioned the retina into nine neuronal classes at birth, increasing to 19
      classes at eye opening and 26 classes by adulthood. Emergence of new cell classes
      was partly attributed to new neuron types and partly to the splitting of classes
      from early ages from refinement of their amino acid profiles. All six GABAergic
      amacrine cell classes and most ganglion cell classes appeared by P7 whilst all
      the glycinergic amacrine cell classes did not appear till adulthood. Separable
      bipolar cell classes were not detected till eye opening. Photoreceptor cell
      classes were detected at P3 but inner and outer segments did not form separable
      classes until adulthood. More importantly, we show that cells which share common
      amino acid profiles also shared cell dispersion patterns. GABAergic amacrine cell
      classes with conventional and displaced counterparts transgressed clonal
      boundaries whereas GABAergic amacrine cell classes found exclusively in the inner
      nuclear layer and all glycinergic amacrine cell classes did not transgress.
      Ganglion cells displayed both dispersion patterns. This study provides a
      comprehensive neurochemical atlas of the developing mouse retina, tracking the
      amino acid levels within distinct neuronal populations and highlighting unique
      migratory patterns within subpopulations of inner retinal neurons. 

PMID- 24041987
TI  - Regulation of system x(c)- in the SOD1-G93A mouse model of ALS.
AB  - The cystine/glutamate antiporter (system xc-) is critical for the generation of
      the antioxidant glutathione by transporting cystine into the cell. At the same
      time, system xc- also releases glutamate, which can potentially lead to
      excitotoxicity. The dual actions of system xc- make it of great interest in any
      disease, like amyotrophic lateral sclerosis (ALS), in which there is evidence of
      the involvement of both oxidative stress and excitotoxicity. The present study
      investigated the regulation of system xc- in the spinal cord of the SOD1-G93A
      transgenic mouse model of ALS. In acute spinal cord slices of 70day old SOD1-G93A
      transgenic mice cystine uptake by system xc- was significantly increased compared
      to age matched non-transgenic mice; but it was not significantly different at 55,
      100, or 130days. The 70day old SOD1-G93A transgenic mice also showed
      significantly increased glutamate release in the presence of cystine. d-Aspartate
      uptake through excitatory amino acid transporters (EAATs), the main mechanism by
      which glutamate is cleared from the extracellular space, was also examined. In
      spinal cord slices of 70day old SOD1-G93A mice no change in d-aspartate uptake
      was found. Together, these findings suggest that at 70days of age, SOD1-G93A
      transgenic mice have increased system xc- activity, but no change in EAAT
      function. These results raise the possibility that excitotoxicity in the SOD1
      G93A transgenic mouse, at least at early time points, may be due to increased
      system xc- activity and not decreased EAAT function. 

PMID- 24041988
TI  - Cyclic AMP promotes axon regeneration, lesion repair and neuronal survival in
      lampreys after spinal cord injury.
AB  - Axon regeneration after spinal cord injury in mammals is inadequate to restore
      function, illustrating the need to design better strategies for improving
      outcomes. Increasing the levels of the second messenger cyclic adenosine
      monophosphate (cAMP) after spinal cord injury enhances axon regeneration across a
      wide variety of species, making it an excellent candidate molecule that has
      therapeutic potential. However, several important aspects of the cellular and
      molecular mechanisms by which cAMP enhances axon regeneration are still unclear,
      such as how cAMP affects axon growth patterns, the molecular components within
      growing axon tips, the lesion scar, and neuronal survival. To address these
      points, we took advantage of the large, identified reticulospinal (RS) neurons in
      lamprey, a vertebrate that exhibits robust axon regeneration after a complete
      spinal cord transection. Application of a cAMP analog, db-cAMP, at the time of
      spinal cord transection increased the number of axons that regenerated across the
      lesion site. Db-cAMP also promoted axons to regenerate in straighter paths,
      prevented abnormal axonal growth patterns, increased the levels of synaptotagmin
      within axon tips, and increased the number of axotomized neurons that survived
      after spinal cord injury, thereby increasing the pool of neurons available for
      regeneration. There was also a transient increase in the number of
      microglia/macrophages and improved repair of the lesion site. Taken together,
      these data reveal several new features of the cellular and molecular mechanisms
      underlying cAMP-mediated enhancement of axon regeneration, further emphasizing
      the positive roles for this conserved pathway. 

PMID- 24041989
TI  - In vivo response of some immune and endocrine variables to LPS in Eurasian perch
      (Perca fluviatilis, L.) and modulation of this response by two corticosteroids,
      cortisol and 11-deoxycorticosterone.
AB  - In fish, the endocrine system, especially corticosteroids pathway, strongly
      interacts with immune system. On the other hand, in vivo co-stimulation of both
      systems is not well documented. To better understand this interaction, we decided
      to evaluate the in vivo effects of both stimulation of the immune system and co
      stimulation of both systems in Eurasian perch juveniles. Fish were injected
      either with 10mgkg(-1) LPS, or with a combination of LPS and 0.8mgkg(-1) cortisol
      or LPS and 0.08mgkg(-1) 11-deoxycorticosterone (DOC) and sampled 1, 3 or 7days
      after injection. LPS affected the immune system by increasing plasma lysozyme
      activity and blood neutrophils populations. During the same time-course, LPS
      decreased the proportion of a mixture of lymphocytes and thrombocytes in blood
      and TNF-alpha expression in spleen. Cortisol modulated the LPS-mediated response
      in TNF-alpha mRNA expression levels in spleen. Contrary to LPS alone, the
      association of LPS with DOC modulated the abundance of complement component 3
      (C3) mRNA in spleen. On the other hand, LPS altered the corticotropic axis by
      decreasing mRNA expression levels of all corticosteroid receptors and of 11beta
      HSD-2 in spleen. Both corticosteroids injected were not able to balance these LPS
      induced suppressive effects on corticosteroid receptors and 11beta-HSD-2
      expression levels in spleen. Contrary to LPS alone, the association of LPS with
      DOC modulated GR-1b expression in gills. These results indicated that LPS is a
      strong modulator of the corticosteroid receptors expression in spleen.
      Furthermore, we report for the first time a LPS-induced decrease of the
      mineralocorticoid receptor expression. Finally, corticosteroids were able to
      modulate the LPS-mediated response at the transcriptional level. 

PMID- 24041990
TI  - Glutaredoxin 1 is a major player in copper metabolism in neuroblastoma cells.
AB  - BACKGROUND: Glutaredoxin 1 (Grx1), a small protein belonging to the thioredoxin
      family, is involved in redox-regulation since it catalyzes the reduction of
      protein disulfides and that of mixed disulfides. It was reported to modulate
      active copper extrusion from cells, by affecting the function of the pumps ATP7A
      and B. These are components of the network of protein chaperones involved in the
      control of the homeostasis of copper, an essential, though harmful, metal.
      However, the effect of Grx1 on copper levels, copper chaperones and copper
      elicited cell toxicity was never investigated. METHODS: In order to investigate
      the effect of Grx1 on copper metabolism, we constitutively overexpressed Grx1 in
      human neuroblastoma SH-SY5Y cells (SH-Grx1 cells) and assessed a number of copper
      related parameters. RESULTS: SH-Grx1 cells show a basal intracellular copper
      level higher than control cells, accumulate more copper upon CuSO4 treatment, but
      are more resistant to copper-induced toxicity. Grx1 shows copper-binding
      properties and copper overload produces a decrease of Grx1 enzyme activity in SH
      Grx1 cells. Finally, Grx1 overexpression decreases copper accumulation in
      mitochondria upon copper overload and modulates the expression of copper
      transporter 1 (Ctr1). CONCLUSION: Altogether, these data demonstrate that Grx1 is
      a major player in copper metabolism in neuronal cells.

PMID- 24041991
TI  - Nucleic acid binding properties of allicin: spectroscopic analysis and estimation
      of anti-tumor potential.
AB  - BACKGROUND: Allicin has received much attention due to its anti-proliferative
      activity and not-well elucidated underlying mechanism of action. This work
      focuses towards determining the cellular toxicity of allicin and understanding
      its interaction with nucleic acid at molecular level. METHODS: MTT assay was used
      to assess the cell viability of A549 lung cancer cells against allicin. Fourier
      transform infrared (FTIR) and UV-visible spectroscopy were used to study the
      binding parameters of nucleic acid-allicin interaction. RESULTS: Allicin inhibits
      the proliferation of cancer cells in a concentration dependent manner. FTIR
      spectroscopy exhibited that allicin binds preferentially to minor groove of DNA
      via thymine base. Analysis of tRNA allicin complex has also revealed that allicin
      binds primarily through nitrogenous bases. Some amount of external binding with
      phosphate backbone was also observed for both DNA and RNA. UV visible spectra of
      both DNA allicin and RNA allicin complexes showed hypochromic shift with an
      estimated binding constant of 1.2*10(4)M(-1) for DNA and 1.06*10(3)M(-1)for RNA
      binding. No major transition from the B-form of DNA and A-form of RNA is observed
      after their interaction with allicin. CONCLUSIONS: The results demonstrated that
      allicin treatment inhibited the proliferation of A549 cells in a dose-dependent
      manner. Biophysical outcomes are suggestive of base binding and helix contraction
      of nucleic acid structure upon binding with allicin. GENERAL SIGNIFICANCE: The
      results describe cytotoxic potential of allicin and its binding properties with
      cellular nucleic acid, which could be helpful in deciphering the complete
      mechanism of cell death exerted by allicin.

PMID- 24041992
TI  - Regulation of the human thioredoxin gene promoter and its key substrates: a study
      of functional and putative regulatory elements.
AB  - BACKGROUND: The thioredoxin system maintains redox balance through the action of
      thioredoxin and thioredoxin reductase. Thioredoxin regulates the activity of
      various substrates, including those that function to counteract cellular
      oxidative stress. These include the peroxiredoxins, methionine sulfoxide
      reductase A and specific transcription factors. Of particular relevance is Redox
      Factor-1, which in turn activates other redox-regulated transcription factors.
      SCOPE OF REVIEW: Experimentally defined transcription factor binding sites in the
      human thioredoxin and thioredoxin reductase gene promoters together with
      promoters of the major thioredoxin system substrates involved in regulating
      cellular redox status are discussed. An in silico approach was used to identify
      potential putative binding sites for these transcription factors in all of these
      promoters. MAJOR CONCLUSIONS: Our analysis reveals that many redox gene promoters
      contain the same transcription factor binding sites. Several of these
      transcription factors are in turn redox regulated. The ARE is present in several
      of these promoters and is bound by Nrf2 during various oxidative stress stimuli
      to upregulate gene expression. Other transcription factors also bind to these
      promoters during the same oxidative stress stimuli, with this redundancy
      supporting the importance of the antioxidant response. Putative transcription
      factor sites were identified in silico, which in combination with specific
      regulatory knowledge for that gene promoter may inform future experiments.
      GENERAL SIGNIFICANCE: Redox proteins are involved in many cellular signalling
      pathways and aberrant expression can lead to disease or other pathological
      conditions. Therefore understanding how their expression is regulated is relevant
      for developing therapeutic agents that target these pathways.

PMID- 24041993
TI  - Stabilities and structures of islet amyloid polypeptide (IAPP22-28) oligomers:
      from dimer to 16-mer.
AB  - BACKGROUND: The formation of amyloid fibrils is associated with many age-related
      degenerative diseases. Nevertheless, the molecular mechanism that directs the
      nucleation of these fibrils is not fully understood. METHODS: Here, we performed
      MD simulations for the NFGAILS motif of hIAPP associated with the type II
      diabetes to estimate the stabilities of hIAPP22-28 protofibrils with different
      sizes: from 2 to 16 chains. In addition, to study the initial self-assembly
      stage, 4 and 8 IAPP22-28 chains in explicit solvent were also simulated. RESULTS:
      Our results indicate that the ordered protofibrils with no more than 16 hIAPP22
      28 chains will be structurally stable in two layers, while one-layer or three
      layer models are not stable as expected. Furthermore, the oligomerization
      simulations show that the initial coil structures of peptides can quickly
      aggregate and convert to partially ordered beta-sheet-rich oligomers.
      CONCLUSIONS: Based on the obtained results, we found that the stability of an
      IAPP22-28 oligomer was not only related with its size but also with its
      morphology. The driving forces to form and stabilize an oligomer are the
      hydrophobic effects and backbone H-bond interaction. Our simulations also
      indicate that IAPP22-28 peptides tend to form an antiparallel strand orientation
      within the sheet. GENERAL SIGNIFICANCE: Our finding can not only enhance the
      understanding about potential mechanisms of hIAPP nuclei formation and the
      extensive structural polymorphisms of oligomers, but also provide valuable
      information to develop potential beta-sheet formation inhibitors against type II
      diabetes.

PMID- 24041994
TI  - Management of risk factors among ambulatory patients at high cardiovascular risk
      in Canada: a follow-up study.
AB  - BACKGROUND: Limited longitudinal data are available on attainment of guideline
      recommended treatment targets among ambulatory patients at high risk for
      cardiovascular events. METHODS: The Vascular Protection registry and the
      Guidelines Oriented Approach to Lipid Lowering registry recruited 8056 ambulatory
      patients at high risk for, or with established cardiovascular disease; follow-up
      was not protocol-mandated. We stratified the study population according to the
      availability of 6-month follow-up data into 2 groups, and compared their clinical
      characteristics, medication profile, and attainment of contemporaneous guideline
      recommended blood pressure (BP) and lipid targets both at enrollment and at 6
      month follow-up. RESULTS: Of the 8056 patients, only 5371 (66.7%) patients had 6
      month follow-up, who had significant increases in the use of statins and
      antihypertensive medications at 6 months compared with at enrollment (all P <
      0.001). Compared with at time of enrollment, more patients attained the BP target
      (45.3% vs 42.3%), low-density lipoprotein cholesterol (LDL-C) target (62.8% vs
      45.8%), and both targets (29.7% vs 21.6%) at 6-month follow-up (all P < 0.001).
      In multivariable analysis, independent predictors of attainment of BP target
      included history of coronary artery disease and heart failure (all P <= 0.001).
      On the other hand, advanced age, diabetes, coronary artery disease, previous
      coronary revascularization, and use of statin therapy were independently
      associated with achievement of LDL-C target (all P < 0.005). CONCLUSIONS: Most (>
      50%) patients without 6-month follow-up did not attain guideline-recommended BP
      and LDL-C targets at enrollment. Although BP and lipid control improved at 6
      months among patients with follow-up, most still failed to achieve optimal BP and
      lipid targets. Effective ongoing quality improvement measures and follow-up are
      warranted.

PMID- 24041995
TI  - Patients, providers, and systems: the complex and unfinished tale of
      socioeconomic status and health.

PMID- 24041996
TI  - Biophysical studies on curcumin-deoxyribonucleic acid interaction: spectroscopic
      and calorimetric approach.
AB  - The interaction of the dietary pigment curcumin with herring testes
      deoxyribonucleic acid was studied by biophysical and microcalorimetric
      techniques. Curcumin bound to DNA exhibiting hypochromic effect in absorbance and
      enhanced intensity of its fluorescence. The binding a affinity value evaluated
      from spectroscopy data was of the order 10(4) M(-1). The quantum efficiency value
      testified the occurrence of energy transfer from the DNA base pairs to the
      curcumin molecules. Displacement studies of DNA bound DAPI, Hoechst and ethidium
      bromide suggested binding of curcumin to be in the minor groove of the DNA.
      Moderate conformational perturbations of the B-form structure of DNA occurred on
      binding. The binding affinity weakened as the DNA GC content enhanced. The
      binding was characterized by negative enthalpy and positive entropy changes; the
      binding affinity from calorimetry was in good agreement with that evaluated from
      the spectral data. The binding was dominated by hydrophobic and other non
      polyelectrolytic forces; the polyelectrolytic forces contributing only a quarter
      to the total Gibbs energy at 50 mM [Na(+)].

PMID- 24041997
TI  - Binding of a double-chain surfactant-cobalt(III) complex to CT DNA: effect of
      beta-cyclodextrin in the medium.
AB  - The interaction of cis-[Co(phen)2(HA)2](ClO4)3, a cationic surfactant complex
      (phen=1,10-phenanthroline, HA=hexadecylamine), with calf thymus DNA has been
      studied by UV-vis absorption, fluorescence spectroscopy, cyclic voltammetry,
      circular dichroism, and viscosity measurements. The spectroscopic studies
      together with cyclic voltammetry and viscosity experiments support that the
      surfactant-cobalt(III) complex binds to calf thymus DNA (CT DNA) by intercalation
      through the aliphatic chain present in the complex into the base pairs of DNA.
      The presence of phenanthroline ligand with larger pi-frame work may also enhance
      intercalation. Besides the effect of binding of surfactant cobalt(III) complex to
      DNA in presence of beta-cyclodextrin has also studied. In presence of beta
      cyclodextrin the binding occurs through surface and (or) groove binding. The
      complex was investigated as one of the potential selective anticancer prodrugs.
      The complex was tested also in vitro on human monolayer tumor cell lines: HepG2
      (human hepatocellular liver carcinoma). 

PMID- 24041998
TI  - Antimicrobial activity of essential oils and five terpenoid compounds against
      Campylobacter jejuni in pure and mixed culture experiments.
AB  - The aim of this study was to examine the antimicrobial potential of three
      essential oils (EOs: tea tree oil, lemon myrtle oil and Leptospermum oil), five
      terpenoid compounds (alpha-bisabolol, alpha-terpinene, cineole, nerolidol and
      terpinen-4-ol) and polyphenol against two strains of Campylobacter jejuni (ACM
      3393 and the poultry isolate C338), Campylobacter coli and other Gram negative
      and Gram positive bacteria. Different formulations of neem oil (Azadirachta
      indica) with these compounds were also tested for synergistic interaction against
      all organisms. Antimicrobial activity was determined by the use of disc diffusion
      and broth dilution assays. All EOs tested were found to have strong antimicrobial
      activity against Campylobacter spp. with inhibitory concentrations in the range
      0.001-1% (v/v). Among the single compounds, terpinen-4-ol showed the highest
      activity against Campylobacter spp. and other reference strains. Based on the
      antimicrobial activity and potential commerciality of these agents, lemon myrtle
      oil, alpha-tops (alpha-terpineol+cineole+terpinen-4-ol) and terpinen-4-ol were
      also evaluated using an in vitro fermentation technique to test antimicrobial
      activity towards C. jejuni in the microbiota from the chicken-caecum. EO
      compounds (terpinen-4-ol and alpha-tops) were antimicrobial towards C. jejuni at
      high doses (0.05%) without altering the fermentation profile. EOs and terpenoid
      compounds can have strong anti-Campylobacter activity without adversely affecting
      the fermentation potential of the chicken-caeca microbiota. EOs and their active
      compounds may have the potential to control C. jejuni colonisation and abundance
      in poultry. 

PMID- 24041999
TI  - VeA and LaeA transcriptional factors regulate ochratoxin A biosynthesis in
      Aspergillus carbonarius.
AB  - Ochratoxin A (OTA) is a mycotoxin with nephrotoxic, teratogenic and immunotoxic
      properties which represents a serious risk for human and animal health.
      Aspergillus carbonarius is considered the main OTA-producing species in grapes
      and products such as raisins, wine or juices, although it has also been isolated
      from coffee, cocoa and cereals. Till now not much information is available about
      regulatory mechanisms of OTA production by A. carbonarius. A better understanding
      of how environmental factors influence OTA production and which genes are
      involved in its regulation could help us design new control strategies. In this
      study, we have evaluated the role of VeA and LaeA transcriptional factors, which
      have been shown to regulate secondary metabolism in response to light in A.
      carbonarius. To this aim, veA and laeA genes were deleted in an ochratoxigenic A.
      carbonarius strain by targeted gene replacement using Agrobacterium tumefaciens
      mediated transformation. Loss of veA and laeA in A. carbonarius yields to an
      organism with slight differences in vegetative growth but a strong reduction in
      conidial production. A drastic decrease of OTA production that ranged from 68.5
      to 99.4% in DeltaveA and DeltalaeA null mutants was also observed, which was
      correlated with a downregulation of a nonribosomal peptide synthetase involved in
      OTA biosynthesis. These findings suggest that VeA and LaeA have an important role
      regulating conidiation and OTA biosynthesis in response to light in A.
      carbonarius in a similar way to other fungi where functions of VeA and LaeA have
      been previously described. This is the first report of a transcriptional factor
      governing the production of OTA by A. carbonarius. 

PMID- 24042000
TI  - Volatile compounds associated with Psychrobacter spp. and Pseudoalteromonas spp.,
      the dominant microbiota of brown shrimp (Crangon crangon) during aerobic storage.
AB  - The spoilage potential of several Psychrobacter and Pseudoalteromonas species
      (Psychrobacter cibarius, Psychrobacter maritimus, Pseudoalteromonas elyakovii,
      Pseudoalteromonas paragorgicola and Pseudoalteromonas nigrifaciens) was
      determined and quantified based on the presence of volatile organic compounds
      (VOCs). Psychrobacter and Pseudoalteromonas species dominate the microbiota of
      cooked brown shrimp (Crangon crangon). Additionally, API ZYM analyses determined
      the species' enzymatic capacity to contribute to spoilage by degrading lipids,
      amino acids and proteins. The bacterial species used in this study were isolated
      from cooked brown shrimp during storage under different storage and processing
      conditions and were selected for analysis of their spoilage potential based on
      their difference in the (GTG)5-rep profile, 16S rRNA and gyrB sequences and API
      ZYM profile. The isolates were inoculated as pure cultures on heat-sterilised
      shrimp. The inoculated samples were stored at 4  degrees C and the production of
      VOCs by the pure strains on the shrimp matrix was identified via gas
      chromatography coupled to mass spectrometry (GC-MS). VOC production was
      quantified daily by selected ion flow tube mass spectrometry (SIFT-MS) until the
      bacterial count exceeded 108-109 cfu/g. The sensory profile of Psychrobacter
      species revealed very low spoilage potential as measured by the production of
      VOCs, but these species may nevertheless contribute to spoilage. Based on the API
      ZYM results, Pseudoalteromonas as well as Psychrobacter species might enhance
      spoilage by breaking down lipids and hydrolysing amino acids and proteins.
      Pseudoalteromonas species, especially Psa. elyakovii and Psa. nigrifaciens, have
      a high spoilage potential and might be responsible for the off-odours produced
      during spoilage of brown shrimp. These isolates produced significant amounts of
      volatile compounds such as sulphides, acetone, ammonia, and ethanol, which are
      all involved in seafood spoilage.

PMID- 24042001
TI  - UV-C light inactivation and modeling kinetics of Alicyclobacillus acidoterrestris
      spores in white grape and apple juices.
AB  - In the present study, the effect of short wave ultraviolet light (UV-C) on the
      inactivation of Alicyclobacillus acidoterrestris DSM 3922 spores in commercial
      pasteurized white grape and apple juices was investigated. The inactivation of A.
      acidoterrestris spores in juices was examined by evaluating the effects of UV
      light intensity (1.31, 0.71 and 0.38 mW/cm2) and exposure time (0, 3, 5, 7, 10,
      12 and 15 min) at constant depth (0.15 cm). The best reduction (5.5-log) was
      achieved in grape juice when the UV intensity was 1.31 mW/cm2. The maximum
      inactivation was approximately 2-log CFU/mL in apple juice under the same
      conditions. The results showed that first-order kinetics were not suitable for
      the estimation of spore inactivation in grape juice treated with UV-light. Since
      tailing was observed in the survival curves, the log-linear plus tail and Weibull
      models were compared. The results showed that the log-linear plus tail model was
      satisfactorily fitted to estimate the reductions. As a non-thermal technology, UV
      C treatment could be an alternative to thermal treatment for grape juices or
      combined with other preservation methods for the pasteurization of apple juice.

PMID- 24042002
TI  - New decontamination method based on caprylic acid in combination with citric acid
      or vanillin for eliminating Cronobacter sakazakii and Salmonella enterica serovar
      Typhimurium in reconstituted infant formula.
AB  - The antimicrobial effects of natural compounds (caprylic acid, CA; citric acid,
      CTA; and vanillin, VNL) on the inactivation of Cronobacter sakazakii and
      Salmonella enterica serovar Typhimurium were examined in reconstituted infant
      formula. The samples were treated with: 1) CA, CTA, or VNL alone (0, 10, 20, 30,
      40, 60, and 80 mM); 2) a combination of CA (10 and 20 mM) and CTA (15 and 30 mM);
      and 3) a combination of CA (10 and 20 mM) and VNL (15 and 30 mM), at mild feeding
      temperatures (40  degrees C and 45  degrees C), and the bacterial populations
      were assayed periodically (0, 5, 10, and 30 min). For both bacteria, the combined
      treatments had marked synergistic antimicrobial effects compared with the sum of
      the effects of each individual treatment. For example, there was no noticeable
      reduction (P > 0.05) in the population of C. sakazakii following an individual
      treatment with 20 mM CA or 30 mM CTA for 5 min at 40  degrees C, whereas the
      population was reduced to undetectable levels (reduction > 7.3 log CFU/ml)
      following treatment with a combination of CA and CTA (20 CA+30 CTA for 5 min at
      40  degrees C). As the temperature increased, the bactericidal effect was
      stronger at all time points with a synergistic effect. In a validation assay
      using a low level inoculum (approximately 103 CFU/ml) of desiccation-stressed
      bacteria in certain conditions, the combined treatments (e.g., CA 10 mM+CTA 30 mM
      for 5 min at 45  degrees C for C. sakazakii, and CA 10mM+VNL 15 mM for 10 min at
      45  degrees C for S. Typhimurium) completely destroyed the bacteria with no
      recovery of cell viability. Disintegration of the membrane and changes in the
      cell structure or morphology, such as plasmolysis and membrane disruption, were
      detected by flow cytometry and electron microscopy, respectively. These methods
      use antimicrobials that could be applied as food additives in infant formula,
      which may help to eliminate bacteria.

PMID- 24042003
TI  - Peripheral vestibular dysfunction is prevalent in older adults experiencing
      multiple non-syncopal falls versus age-matched non-fallers: a pilot study.
AB  - BACKGROUND: vestibular disorders are common in the general population, increasing
      with age. However, it is unknown whether older adults who fall have a higher
      proportion of vestibular impairment compared with age-matched older adult non
      fallers. OBJECTIVE: to identify whether a greater proportion of older adult
      fallers have a peripheral vestibular impairment compared with age-matched healthy
      controls. DESIGN: case-controlled study. SETTING: tertiary falls and neuro
      otology clinics and local community centres, London, UK. PARTICIPANTS AND
      METHODS: community-dwelling older adults experiencing: (i) >=2 unexplained falls
      within the previous 12-months (Group F, n = 25), (ii) a confirmed peripheral
      vestibular disorder (Group PV, n = 15) and (iii) healthy non-fallers (Group H, n
      = 16). All the participants completed quantitative vestibular function tests, the
      functional gait assessment (FGA), physiological profile assessment (PPA) and
      subjective measures for common vestibular symptoms (i.e. giddiness), balance
      confidence during daily activities and psychological state. RESULTS: a clinically
      significant vestibular impairment was noted for 80% (20/25) of Group F compared
      with 18.75% (3/16) for Group H (P < 0.01). Group F performed less well in complex
      gait tasks (FGA), and reported a greater number of falls than both Groups H and
      PV (P < 0.05). Vestibular symptom scores showed no significant difference between
      Groups F and PV. CONCLUSION: vestibular dysfunction is significantly more
      prevalent in older adult fallers versus non-fallers. Individuals referred to a
      falls clinic are older, more impaired and report more falls than those referred
      to a neuro-otology department. A greater awareness of vestibular impairments may
      lead to more effective management and treatment for older adult fallers.

PMID- 24042004
TI  - Sensorimotor and psychosocial determinants of 3-year incident mobility disability
      in middle-aged and older adults.
AB  - OBJECTIVE: to identify sensorimotor and psychosocial determinants of 3-year
      incident mobility disability. DESIGN: prospective. SETTING: population-based
      sample of community-dwelling older persons. PARTICIPANTS: community-living middle
      aged and older persons (age: 50-85 years) without baseline mobility disability (n
      = 622). MEASUREMENTS: mobility disability, defined as self-reported inability to
      walk a quarter mile without resting or inability to walk up a flight of stairs
      unsupported, was ascertained at baseline and 3-year follow-up. Potential baseline
      determinant characteristics included demographics, education, social support,
      financial condition, knee extensor strength, visual contrast sensitivity,
      cognition, depression, presence of chronic conditions and history of falls.
      RESULTS: a total of 13.5% participant reported 3-year incident mobility
      disability. Age >=75 years, female sex, knee extensor strength in the lowest
      quartile, visual contrast sensitivity <1.7 on the Pelli-Robson chart or
      significant depressive symptoms (CESD score >16) were independent determinants of
      3-year incident mobility disability (ORs 1.84-16.51). CONCLUSIONS: low visual
      contrast sensitivity, poor knee extensor strength and significant depressive
      symptoms are independent determinants of future onset of mobility disability.

PMID- 24042005
TI  - Synthesis and assessment of catechol diether compounds as inhibitors of
      trypanosomal phosphodiesterase B1 (TbrPDEB1).
AB  - Human African trypanosomiasis (HAT) is a parasitic neglected tropical disease
      that affects 10,000 patients each year. Current treatments are sub-optimal, and
      the disease is fatal if not treated. Herein, we report our continuing efforts to
      repurpose the human phosphodiesterase 4 (hPDE4) inhibitor piclamilast to target
      trypanosomal phosphodiesterase TbrPDEB1. We prepared a range of substituted
      heterocyclic replacements for the 4-amino-3,5-dichloro-pyridine headgroup of
      piclamilast, and found that these compounds exhibited weak inhibitory activity of
      TbrPDEB1. 

PMID- 24042006
TI  - Imidazo[4,5-b]pyridine inhibitors of B-Raf kinase.
AB  - This Letter details the synthesis and evaluation of imidazo[4,5-b]pyridines as
      inhibitors of B-Raf kinase. These compounds bind in a DFG-in, alphaC-helix out
      conformation of B-Raf, which is a binding mode associated with significant kinase
      selectivity. Structure-activity relationship studies involved optimization of the
      ATP-cleft binding region of these molecules, and led to compound 23, an inhibitor
      with excellent enzyme/cell potency, and kinase selectivity. 

PMID- 24042007
TI  - Inhibitory constituents from the aerial parts of Polygala tenuifolia on LPS
      induced NO production in BV2 microglia cells.
AB  - Five new phenolic glycosides, tenuisides A-E (1-5), and a new megastigmane
      glycoside, tenuiside F (6), along with seventeen known compounds (7-23) were
      isolated from the aerial parts of Polygala tenuifolia Willd. Their structures
      were established by detailed analysis of NMR and HRESIMS spectroscopic data, and
      the absolute configurations of compounds 5 and 6 were determined by CD spectra
      and in-NMR-tube Mosher's method. The inhibitory effects of these compounds were
      evaluated on NO production in LPS-activated BV-2 microglia cells. Compound 17
      showed the strongest activity, with an IC50 value of 7.4MUM, while compounds 1,
      8, 14, and 18 showed the moderate activities, with IC50 values of 16.2-38.5MUM.
      And their primary structure-activity relationships (SARs) of NO inhibitory
      effects were also briefly discussed. 

PMID- 24042008
TI  - [(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic acid
      derivatives; HIF prolyl 4-hydroxylase inhibitors as oral erythropoietin
      secretagogues.
AB  - A new series of PHD (HIF prolyl 4-hydroxylase) inhibitors was designed based on
      the X-ray co-crystal structure of FG-2216. Using a lead generation process, a
      series of [(4-Hydroxyl-benzo[4,5]thieno[3,2-c]pyridine-3-carbonyl)-amino]-acetic
      acid derivatives was developed as potent PHD2 inhibitors. This class of compounds
      also showed the ability to stabilize HIF-alpha, to stimulate EPO secretion in in
      vitro studies, and to increase hematocrit, red blood cell count, and hemoglobin
      levels in an animal efficacy study. 

PMID- 24042009
TI  - Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors.
AB  - A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of
      Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was
      discovered. Structure-based design strategies were applied to significantly
      improve enzyme potency and the polarity of the molecule was adjusted to gain
      cellular activity. The crystal structures of two representative inhibitors bound
      to Jak1 were obtained to enable SAR exploration. 

PMID- 24042011
TI  - [Axillary artery pseudo-aneurysm secondary to shoulder dislocation in children].
AB  - Axillary artery injury following anterior dislocation of the shoulder in children
      is a rare complication often considered as iatrogenic. We report the case of a
      pseudo-aneurysm of the axillary artery in a 5-year-old boy that appeared four
      months after a shoulder dislocation that was reduced in an ambulatory setting.
      Although this is an uncommon vascular complication, we emphasize the need for
      short-term and long-term follow-up in these children to avoid missing a pseudo
      aneurysm of the axillary artery. 

PMID- 24042010
TI  - Microwave accelerated synthesis of isoxazole hydrazide inhibitors of the system
      xc- transporter: Initial homology model.
AB  - Microwave accelerated reaction system (MARS) technology provided a good method to
      obtain selective and open isoxazole ligands that bind to and inhibit the Sxc-
      antiporter. The MARS provided numerous advantages, including: shorter time,
      better yield and higher purity of the product. Of the newly synthesized series of
      isoxazoles the salicyl hydrazide 6 exhibited the highest level of inhibitory
      activity in the transport assay. A homology model has been developed to summarize
      the SAR results to date, and provide a working hypothesis for future studies.

PMID- 24042012
TI  - Strength training affects lower extremity gait kinematics, not kinetics, in
      people with diabetic polyneuropathy.
AB  - Increased forefoot loading in diabetic polyneuropathy plays an important role in
      the development of plantar foot ulcers and can originate from alterations in
      muscle strength, joint moments and gait pattern. The current study evaluated
      whether strength training can improve lower extremity joint moments and
      spatiotemporal gait characteristics in patients with diabetic polyneuropathy. An
      intervention group receiving strength training during 24 weeks and a control
      group receiving no intervention. Measurements were performed in both groups at
      t=0, t=12, t=24 and t=52 weeks at an individually preferred and standardized
      imposed gait velocity. The strength training did not affect the maximal amplitude
      of hip, knee and ankle joint moments, but did result in an increase in stance
      phase duration, stride time and stride length of approximately 5%, during the
      imposed gait velocity. In addition, both groups increased their preferred gait
      velocity over one year. Future longitudinal studies should further explore the
      possible effects of strength training on spatiotemporal gait characteristics. The
      current study provides valuable information on changes in gait velocities and the
      progressive lower extremity problems in patients with polyneuropathy.

PMID- 24042013
TI  - Further characterization of Tsol-p27 as a diagnostic antigen in sub-Saharan
      Africa.
AB  - Commercial antigens used to diagnose human neurocysticercosis are obtained from
      either a soluble parasite extract or a parasite-derived glycoprotein fraction.
      The aim of the present study was to identify antigenic proteins as potential
      diagnostic candidates in Mozambique. Soluble proteins from Taenia solium
      cysticerci were separated by two-dimensional electrophoresis and blotted onto
      nitrocellulose membranes. Subtracted hybridization was performed with serum
      samples obtained from patients with neurocysticercosis (NCC) and from a NCC
      negative control group. Six antigenic proteins were identified and sequenced by
      liquid chromatography-mass spectrometry. Among these we found Tsol-p27, which was
      previously identified as a diagnostic candidate in a study conducted in
      Nicaragua, Central America. Here, we evaluated Tsol-p27 and the antigen cC1 as
      potential recombinant diagnostic reagents, and also investigated the localization
      and partial function of Tsol-p27. Immunoblotting demonstrated that Tsol-p27 was
      recognized by all 10 serum samples from NCC-positive individuals, whereas cC1 was
      identified by only five of the 10 positive sera. None of the antigens were
      recognized by negative control sera. Despite the limited number of serum samples
      evaluated in this study, the results suggest that Tsol-p27 can be a suitable
      candidate for diagnosis of human NCC, not only in Central America but also in sub
      Saharan Africa. 

PMID- 24042014
TI  - Pericytes modulate endothelial sprouting.
AB  - AIM: Angiogenic sprouts arise from microvessels formed by endothelial cells (ECs)
      invested by pericytes (PCs). The aim of this study was to examine the role of PCs
      in angiogenic sprouting, an understudied phenomenon. METHODS AND RESULTS: We
      adapted a human EC spheroid model to examine PC effects on vascular endothelial
      growth factor-A-induced EC sprouting in vitro by using Bcl-2-transduced human
      umbilical vein ECs to reduce apoptosis in collagen gels. Human placental PCs,
      separated from endothelial spheroids by a transwell, or addition of PC
      conditioned media increased EC sprouting primarily through hepatocyte growth
      factor (HGF). Mixed endothelial-PC spheroids formed similar numbers of
      endothelial sprouts as endothelial spheroids but the sprouts from mixed spheroids
      were invested by PCs within 24 h. PCs were recruited to the sprouts by platelet
      derived growth factor (PDGF)-BB; inhibition of PDGF signalling reduced PC
      coverage and increased EC sprouting. Transplanted endothelial spheroids give rise
      to sprouts in vivo that evolve into perfused microvessels. Mixed endothelial-PC
      spheroids form similar numbers of microvessels as endothelial-only spheroids, but
      acquire human PC investment and have reduced average lumen diameter. CONCLUSIONS:
      PCs promote endothelial sprouting by elaborating HGF, but when recruited to
      invest endothelial sprouts by PDGF-BB, limit the extent of sprouting in vitro and
      lumen diameter in vivo.

PMID- 24042015
TI  - Brahma-related gene 1 (Brg1) epigenetically regulates CAM activation during
      hypoxic pulmonary hypertension.
AB  - AIMS: Establishment of an inflammatory milieu following elevated leukocyte
      adhesion to the vascular endothelium, which is mediated by transcriptional
      activation of cell adhesion molecules (CAMs), contributes to the pathogenesis of
      chronic hypoxia-induced pulmonary hypertension (HPH). The epigenetic switch that
      dictates CAM transactivation in response to hypoxia in endothelial cells leading
      up to HPH is not fully appreciated. METHODS AND RESULTS: We report here that
      brahma-related gene 1 (Brg1) and brahma (Brm), two catalytic components of the
      mammalian chromatin remodelling complex, were induced in cultured endothelial
      cells challenged with hypoxia in vitro as well as in pulmonary arteries in an
      animal model of HPH. Over-expression of Brg1/Brm enhanced, while the depletion of
      Brg1/Brm attenuated, CAM transactivation and adhesion of leukocytes. Endothelial
      specific deletion of Brg1/Brm ameliorated vascular inflammation and HPH in mice.
      Chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that hypoxia up
      regulated the occupancies of Brg1 and Brm on CAM promoters in a nuclear factor
      kappaB (NF-kappaB) -dependent manner. Finally, Brg1 and Brm activated CAM
      transcription by altering the chromatin structure surrounding the CAM promoters.
      CONCLUSION: Our data suggest that Brg1 provides the crucial epigenetic link to
      hypoxia-induced CAM induction and leukocyte adhesion that engenders endothelial
      malfunction and pathogenesis of HPH. As such, targeting Brg1 in endothelial cells
      may yield promising strategies in the intervention and/or prevention of HPH.

PMID- 24042016
TI  - Electrophysiological integration and action potential properties of transplanted
      cardiomyocytes derived from induced pluripotent stem cells.
AB  - AIMS: Induced pluripotent stem cell-derived cardiomyocytes (iPSCM) are regarded
      as promising cell type for cardiac cell replacement therapy. We investigated long
      term electrophysiological integration and maturation of transplanted iPSCM, which
      are essential for therapeutic benefit. METHODS AND RESULTS: Murine iPSCM
      expressing enhanced green fluorescent protein and a puromycin resistance under
      control of the alpha-myosin heavy chain promoter were purified by antibiotic
      selection and injected into adult mouse hearts. After 6-12 days, 3-6 weeks, or 6
      8 months, viable slices of recipient hearts were prepared. Slices were focally
      stimulated by a unipolar electrode placed in host tissue, and intracellular
      action potentials (APs) were recorded with glass microelectrodes in transplanted
      cells and neighbouring host tissue within the slices. Persistence and electrical
      integration of transplanted iPSCM into recipient hearts could be demonstrated at
      all time points. Quality of coupling improved, as indicated by a maximal
      stimulation frequency without conduction blocks of 5.77 +/- 0.54 Hz at 6-12 days,
      8.98 +/- 0.38 Hz at 3-6 weeks and 10.82 +/- 1.07 Hz at 6-8 months after
      transplantation. AP properties of iPSCM became more mature from 6-12 days to 6-8
      months after transplantation, but still differed significantly from those of host
      APs. CONCLUSION: Transplanted iPSCM can persist in the long term and integrate
      electrically into host tissue, supporting their potential for cell replacement
      therapy. Quality of electrical integration improves between 6-12 days and 6-8
      months after transplantation, and there are signs of an electrophysiological
      maturation. However, even after 6-8 months, AP properties of transplanted iPSCM
      differ from those of recipient cardiomyocytes.

PMID- 24042017
TI  - Myocardial energy shortage and unmet anaplerotic needs in the fasted long-chain
      acyl-CoA dehydrogenase knockout mouse.
AB  - AIMS: The aim of this animal study is to assess fasting-induced changes in
      myocardial substrate metabolism and energy status as a consequence of
      mitochondrial long-chain fatty acid beta-oxidation deficiency, using magnetic
      resonance spectroscopy (MRS). METHODS AND RESULTS: Carbon-13 ((13)C) MRS of
      hyperpolarized [1-(13)C]pyruvate was used to assess in vivo pyruvate
      dehydrogenase (PDH) activity in fed and fasted wild-type (WT) mice and long-chain
      acyl-CoA dehydrogenase knockout (LCAD KO) mice. PDH activity decreased after
      fasting in both genotypes, but was 2.7-fold higher in fasted LCAD KO mice
      compared with fasted WT mice. Incorporation of the (13)C label into the
      myocardial malate and aspartate pools in fasted LCAD KO mice demonstrates
      enhanced activity of anaplerotic pathways in fasted LCAD KO hearts. These
      findings were corroborated by ex vivo assays revealing partially depleted pools
      of citric acid cycle intermediates in fasted LCAD KO myocardium, suggesting an
      increased, but unmet need for anaplerosis. The in vivo myocardial energy status,
      assessed using phosphorous-31 ((31)P) MRS, was lower in fasted LCAD KO mice than
      in fasted WT mice. CONCLUSION: This study revealed that the heart of fasted LCAD
      KO mice has an elevated reliance on glucose oxidation, in combination with an
      unmet demand for myocardial anaplerosis. Due to a lack of substrate availability,
      the sustained myocardial glucose uptake and PDH activity in LCAD KO mice are
      ineffective to maintain metabolic homeostasis during fasting, which is reflected
      by an impaired myocardial energy status in fasted LCAD KO mice.

PMID- 24042018
TI  - A diet supplemented with ALA-rich flaxseed prevents cardiomyocyte apoptosis by
      regulating caveolin-3 expression.
AB  - AIMS: n-3 polyunsaturated fatty acids (PUFAs) induce beneficial effects on the
      heart, but the mechanisms through which these effects are operated are not
      completely clarified yet. Among others, cardiac diseases are often associated
      with increased levels of cytokines, such as tumour necrosis factor-alpha (TNF),
      that cause degeneration and death of cardiomyocytes. The present study has been
      carried out to investigate (i) the potential anti-apoptotic effects induced by
      the n-3 polyunsaturated alpha-linolenic acid (ALA) in experimental models of
      cardiac diseases characterized by high levels of TNF, and (ii) the potential role
      of caveolin-3 (Cav-3) in the mechanisms involved in this process. METHODS AND
      RESULTS: An ALA-rich flaxseed diet, administered from weaning to hereditary
      cardiomyopathic hamsters, prevented the onset of myocardial apoptosis associated
      with high plasma and tissue levels of TNF preserving caveolin-3 expression. To
      confirm these findings, isolated neonatal mouse cardiomyocytes were exposed to
      TNF to induce apoptosis. ALA pre-treatment greatly enhanced Cav-3 expression
      hampering the internalization of the caveolar TNF receptor and, thus, determining
      the abortion of the apoptotic vs. survival cascade. CONCLUSION: This study
      unveiled the Cav-3 pivotal role in defending cardiomyocytes against the TNF pro
      apoptotic action and the ALA capacity to regulate this mechanism preventing
      cardiac degenerative diseases.

PMID- 24042019
TI  - LMX1B mutation with residual transcriptional activity as a cause of isolated
      glomerulopathy.
AB  - BACKGROUND: Nail-patella syndrome (NPS) is a rare autosomal-dominant disorder
      caused by LMX1B mutation. In patients with the renal lesions typical of NPS
      without skeletal or nail findings, it is described as nail-patella-like renal
      disease (NPLRD). However, the pathogenesis of NPLRD is largely unknown. METHODS:
      A 6-year-old girl with microscopic haematuria and mild proteinuria was diagnosed
      with NPLRD because of an aberrantly thickened glomerular basement membrane (GBM)
      and deposition of Type III collagen in the GBM observed by electron microscopy.
      Immunohistological analyses of podocyte protein expression were performed on
      biopsy tissues. Sequence analysis of LMX1B was performed, and the functional
      consequences of the detected mutation were analysed by luciferase reporter assay.
      RESULTS: When analysing molecules that are important for podocyte development,
      maintenance and maturation, CD2AP expression was found to be altered in the
      podocytes. A novel LMX1B missense mutation (R246Q) was identified. Functional
      analyses revealed partial but significant impairment of R246Q transcriptional
      activity. However, no dominant-negative effect of R246Q was detected, which
      suggests that NPLRD is caused by LMX1B haploinsufficiency. CONCLUSIONS: This is
      the first report on LMX1B mutation identified in a patient with NPLRD. Residual
      transcriptional activity would account for normality of the nails and patella in
      this case. Genetic and pathological analyses of additional cases would clarify
      the role of LMX1B in glomerulopathy without systemic symptoms, which, together
      with nephropathy in NPS, can be designated as 'LMX1B nephropathy'.

PMID- 24042020
TI  - Expression of the transcriptional regulator snail1 in kidney transplants
      displaying epithelial-to-mesenchymal transition features.
AB  - BACKGROUND: The epithelial response to injury is stereotypical and reminiscent of
      epithelial-to-mesenchymal transitions (EMTs), such as those observed during
      embryogenesis and tumour metastasis. In the context of solid organ
      transplantation, EMT-like features are often acquired by epithelial cells and are
      predictive of graft fibrosis. Here, we studied the possible involvement of
      several major transcriptional regulators, including snail1, phospho-Smad 2/3 and
      zeb1, in EMT induction in human renal grafts. METHODS: We used
      immunohistochemistry to detect the presence of these EMT transcriptional
      regulators along with that of two validated EMT markers (intra-cytoplasmic
      translocation of beta-catenin, de novo expression of vimentin), in 103 renal
      graft biopsy samples taken for routine surveillance or for a clinical indication.
      RESULTS: We observed the nuclear accumulation of snail1 and phospho-smad2/3 in
      tubular cells displaying EMT. The level of snail1 was significantly correlated
      with the scores of EMT markers (beta-catenin: rho = 0.94, P < 0.0001; vimentin:
      rho = 0.93, P < 0.0001) and with deteriorated graft function and proteinuria at
      the time of biopsy. Furthermore, intense staining for both snail1 and vimentin in
      tubular cells (>=10% of tubules) was predictive of graft dysfunction 21 months
      post-biopsy, independently of the other known risk factor for long-term graft
      dysfunction. In contrast, in both normal and diseased graft, zeb1 expression was
      detected exclusively in the endothelial cells of glomeruli and peritubular
      capillaries. CONCLUSION: This study suggests that snail1 is closely related to
      the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts
      and predictive of graft function loss.

PMID- 24042021
TI  - Effects of uric acid-lowering therapy on renal outcomes: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Non-randomized studies suggest an association between serum uric acid
      levels and progression of chronic kidney disease (CKD). The aim of this
      systematic review is to summarize evidence from randomized controlled trials
      (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal
      outcomes. METHODS: Medline, Excerpta Medical Database and Cochrane Central
      Register of Controlled Trials were searched with English language restriction for
      RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment
      on renal outcomes. Treatment effects were summarized using random-effects meta
      analysis. RESULTS: Eight trials (476 participants) evaluating allopurinol
      treatment were eligible for inclusion. There was substantial heterogeneity in
      baseline kidney function, cause of CKD and duration of follow-up across these
      studies. In five trials, there was no significant difference in change in
      glomerular filtration rate from baseline between the allopurinol and control arms
      [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9,
      7.1; heterogeneity chi2=1.9, I2=0%, P=0.75]. In three trials, allopurinol
      treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL,
      95% CI -0.8, -0.0 mg/dL; heterogeneity chi2=3, I2=34%, P=0.22). Allopurinol had
      no effect on proteinuria and blood pressure. Data for effects of allopurinol
      therapy on progression to end-stage kidney disease and death were scant.
      Allopurinol had uncertain effects on the risks of adverse events. CONCLUSIONS:
      Uric acid-lowering therapy with allopurinol may retard the progression of CKD.
      However, adequately powered randomized trials are required to evaluate the
      benefits and risks of uric acid-lowering therapy in CKD.

PMID- 24042022
TI  - Podocyte expression of nonmuscle myosin heavy chain-IIA decreases in idiopathic
      nephrotic syndrome, especially in focal segmental glomerulosclerosis.
AB  - BACKGROUND: Previous studies have identified significant associations between the
      development of idiopathic focal segmental glomerulosclerosis (FSGS) and MYH9
      encoding nonmuscle myosin heavy chain-IIA (NMMHC-IIA). However, these studies
      focused only on the linkage of MYH9 polymorphisms and development of FSGS. There
      have been no reports on pathological changes of NMMHC-IIA in human glomerular
      diseases. Here we report on the precise localization of NMMHC-IIA in podocytes
      and changes in NMMHC-IIA expression in pathological states in rats and humans.
      METHODS: Immunocytochemical (immunofluorescence and immunoelectron microscopy)
      studies were performed to determine the precise localization of NMMHC-IIA.
      Expression levels of NMMHC-IIA were investigated in puromycin aminonucleoside
      (PAN)-treated rats; and expression levels of NMMHC-IIA and other podocyte-related
      proteins were investigated in glomeruli of patients with idiopathic FSGS and
      other heavy proteinuric glomerular diseases. RESULTS: NMMHC-IIA was located
      primarily at the cell body and primary processes of podocytes; this localization
      is distinct from other podocyte-related molecules causing hereditary FSGS. In PAN
      treated rat kidneys, expression levels of NMMHC-IIA in podocytes decreased.
      Immunohistochemical analysis revealed that expression levels of NMMHC-IIA
      markedly decreased in idiopathic nephrotic syndrome, especially FSGS, whereas it
      did not change in other chronic glomerulonephritis showing apparent proteinuria.
      Changes in NMMHC-IIA expression were observed in glomeruli where expression of
      nephrin and synaptopodin was maintained. CONCLUSIONS: Considering previous genome
      wide association studies and development of FSGS in patients with MYH9 mutations,
      the characteristic localization of NMMHC-IIA and the specific decrease in NMMHC
      IIA expression in idiopathic nephrotic syndrome, especially FSGS, suggest the
      important role of NMMHC-IIA in the development of FSGS.

PMID- 24042023
TI  - Drug dissolution: significance of physicochemical properties and physiological
      conditions.
AB  - Oral bioavailability of a drug is determined by a number of properties, including
      drug dissolution rate, solubility, intestinal permeability and pre-systemic
      metabolism. Frequently, the rate limiting step in drug absorption from the
      gastrointestinal tract is drug release and drug dissolution from the dosage form.
      Therapeutic agents with aqueous solubilities less than 100MUg/ml often present
      dissolution limitations to absorption. Physicochemical, formulation-related and
      physiological factors can all influence drug dissolution. In this review, the
      authors will discuss the important physicochemical properties of a drug and
      physiological conditions in the gastrointestinal tract that play an important
      part in drug dissolution and absorption processes and, consequently, the
      bioavailability of a drug. 

PMID- 24042024
TI  - Non-steroidal anti-inflammatory drug use and cervical cancer risk: a case-control
      study using the Clinical Practice Research Datalink.
AB  - PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) have many
      anticarcinogenic properties via the inhibition of cyclooxygenase 2 (COX-2). Only
      one study, a cohort study examining risk of all cancers, investigated their role
      in cervical cancer with inconsistent findings between non-aspirin NSAIDs and
      aspirin. The aim of this study was to further investigate NSAID/aspirin use and
      cervical cancer risk. METHODS: Using the United Kingdom Clinical Practice
      Research Datalink, 724 women diagnosed with cervical cancer between 1 January,
      1995 and December 2010 were compared to 3479 women (without cervical cancer)
      matched on year of birth and general practice. Conditional logistic regression
      analysis adjusted for smoking, sexually transmitted infections, HRT and
      contraceptive use, was used to calculate odds ratios (OR) and 95% confidence
      intervals (CI) for cervical cancer risk among users of any oral NSAIDs, non
      aspirin NSAIDs and aspirin, as assessed from primary care prescribing data.
      RESULTS: Excluding the year prior to diagnosis, there was no association in
      adjusted analyses between ever vs. never use of an NSAID (OR 0.92, 95% CI 0.77
      1.09), non-aspirin NSAID (OR 0.95, 95% CI 0.80-1.13) or low-dose aspirin (OR
      1.07, 0.80-1.44) and cervical cancer risk. In analysis of daily defined doses,
      there was no association with cervical cancer risk comparing the highest users to
      non-users of NSAIDs (OR 0.98, 95% CI 0.69-1.39) or non-aspirin NSAIDs (OR 1.00,
      95% CI 0.70-1.43) or low-dose aspirin (OR 1.04, 95% CI 0.59-1.81). CONCLUSION:
      This large historical cohort study found no evidence of an association between
      non-aspirin NSAID or aspirin use and cervical cancer risk.

PMID- 24042025
TI  - Estimating the proportion cured of cancer: some practical advice for users.
AB  - BACKGROUND: Cure models can provide improved possibilities for inference if used
      appropriately, but there is potential for misleading results if care is not
      taken. In this study, we compared five commonly used approaches for modelling
      cure in a relative survival framework and provide some practical advice on the
      use of these approaches. PATIENTS AND METHODS: Data for colon, female breast, and
      ovarian cancers were used to illustrate these approaches. The proportion cured
      was estimated for each of these three cancers within each of three age groups. We
      then graphically assessed the assumption of cure and the model fit, by comparing
      the predicted relative survival from the cure models to empirical life table
      estimates. RESULTS: Where both cure and distributional assumptions are
      appropriate (e.g., for colon or ovarian cancer patients aged <75 years), all five
      approaches led to similar estimates of the proportion cured. The estimates varied
      slightly when cure was a reasonable assumption but the distributional assumption
      was not (e.g., for colon cancer patients >=75 years). Greater variability in the
      estimates was observed when the cure assumption was not supported by the data
      (breast cancer). CONCLUSIONS: If the data suggest cure is not a reasonable
      assumption then we advise against fitting cure models. In the scenarios where
      cure was reasonable, we found that flexible parametric cure models performed at
      least as well, or better, than the other modelling approaches. We recommend that,
      regardless of the model used, the underlying assumptions for cure and model fit
      should always be graphically assessed.

PMID- 24042026
TI  - Prevalence and risk factors for canine obesity surveyed in veterinary practices
      in Beijing, China.
AB  - An epidemiological survey of canine obesity was carried out in Beijing, China.
      Cases (n=2391, 7 districts) were collected at 14 animal hospitals between April
      2008 and April 2011. The body condition score (scales of 1-5) was used to assess
      obesity of the dogs (Burkholder and Toll, 2000; Laflamme, 1997). Obesity rates
      were analyzed with respect to breed, age, sex, neutering, food control, feeding
      frequency, reproduction status, food type, nutritional supplements, living
      environment, feeding time, number of pets per household, feeding purpose,
      activity control, exercise duration, exercise status and exercise type. The
      overall canine obesity rate was 44.4% in this survey. The risk factors for dog
      obesity were food type (non-commercial food, OR=1.377, p<0.05), age (1-2 y,
      OR=0.044, p<0.001), activity control (free activity, OR=0.685, p<0.05), neutering
      (intact, OR=0.629, p<0.01), sex (male, OR=0.628, p<0.001), feeding frequency
      (Once per day, OR=0.521, p<0.01). By dog breed, prevalence of obesity was high in
      pugs (70.7%), Cocker Spaniel (69.4%), Pekingese (51.9%), Pomeranian (54.6%) and
      Golden Retriever (51.9%). This is the first report of the epidemiology of canine
      obesity in China.

PMID- 24042027
TI  - Reply to the letter to the editor by Bouyer et al. (2013).

PMID- 24042028
TI  - Do testosterone and brain-derived neurotrophic factor interactions play a role in
      the pathophysiology of suicidal behavior?

PMID- 24042029
TI  - Negotiating for more: the multiple equivalent simultaneous offer.
AB  - Whether a doctor, professional baseball manager, or a politician, having
      successful negotiation skills is a critical part of being a leader. Building upon
      prior journal articles on negotiation strategy, the author presents the concept
      of the multiple equivalent simultaneous offer (MESO). The concept of a MESO is
      straightforward: as opposed to making a single offer, make multiple offers with
      several variables. Each offer alters the different variables, such that the end
      result of each offer is equivalent from the perspective of the party making the
      offer. Research has found several advantages to the use of MESOs. For example,
      using MESOs, an offer was more likely to be accepted, and the counterparty was
      more likely to be satisfied with the negotiated deal. Additional benefits have
      been documented as well, underscoring why a prepared radiology business leader
      should understand the theory and practice of MESO. 

PMID- 24042030
TI  - Textural features of pretreatment 18F-FDG PET/CT images: prognostic significance
      in patients with advanced T-stage oropharyngeal squamous cell carcinoma.
AB  - Previous studies have shown that total lesion glycolysis (TLG) may serve as a
      prognostic indicator in oropharyngeal squamous cell carcinoma (OPSCC). We sought
      to investigate whether the textural features of pretreatment (18)F-FDG PET/CT
      images can provide any additional prognostic information over TLG and clinical
      staging in patients with advanced T-stage OPSCC. METHODS: We retrospectively
      analyzed the pretreatment (18)F-FDG PET/CT images of 70 patients with advanced T
      stage OPSCC who had completed concurrent chemoradiotherapy, bioradiotherapy, or
      radiotherapy with curative intent. All of the patients had data on human
      papillomavirus (HPV) infection and were followed up for at least 24 mo or until
      death. A standardized uptake value (SUV) of 2.5 was taken as a cutoff for tumor
      boundary. The textural features of pretreatment (18)F-FDG PET/CT images were
      extracted from histogram analysis (SUV variance and SUV entropy), normalized gray
      level cooccurrence matrix (uniformity, entropy, dissimilarity, contrast,
      homogeneity, inverse different moment, and correlation), and neighborhood gray
      tone difference matrix (coarseness, contrast, busyness, complexity, and
      strength). Receiver-operating-characteristic curves were used to identify the
      optimal cutoff values for the textural features and TLG. RESULTS: Thirteen
      patients were HPV-positive. Multivariate Cox regression analysis showed that age,
      tumor TLG, and uniformity were independently associated with progression-free
      survival (PFS) and disease-specific survival (DSS). TLG, uniformity, and HPV
      positivity were significantly associated with overall survival (OS). A prognostic
      scoring system based on TLG and uniformity was derived. Patients who presented
      with TLG > 121.9 g and uniformity <= 0.138 experienced significantly worse PFS,
      DSS, and OS rates than those without (P < 0.001, < 0.001, and 0.002,
      respectively). Patients with TLG > 121.9 g or uniformity <= 0.138 were further
      divided according to age, and different PFS and DSS were observed. CONCLUSION:
      Uniformity extracted from the normalized gray-level cooccurrence matrix
      represents an independent prognostic predictor in patients with advanced T-stage
      OPSCC. A scoring system was developed and may serve as a risk-stratification
      strategy for guiding therapy.

PMID- 24042031
TI  - Heterogeneity in intratumor correlations of 18F-FDG, 18F-FLT, and 61Cu-ATSM PET
      in canine sinonasal tumors.
AB  - Intratumor heterogeneity in biologic properties and in relationships between
      various phenotypes may present a challenge for biologically targeted therapies.
      Understanding the relationships between different phenotypes in individual tumor
      types could help inform treatment selection. The goal of this study was to
      characterize spatial correlations of glucose metabolism, proliferation, and
      hypoxia in 2 histologic types of tumors. METHODS: Twenty canine veterinary
      patients with spontaneously occurring sinonasal tumors (13 carcinomas and 7
      sarcomas) were imaged with (18)F-FDG, (18)F-labeled 3'-deoxy-3'-fluorothymidine
      ((18)F-FLT), and (61)Cu-labeled diacetyl-bis(N(4)-methylthiosemicarbazone)
      ((61)Cu-ATSM) PET/CT on 3 consecutive days. Precise positioning and
      immobilization techniques coupled with anesthesia enabled motionless scans with
      repeatable positioning. Standardized uptake values (SUVs) of gross sarcoma and
      carcinoma volumes were compared by use of Mann-Whitney U tests. Patient images
      were rigidly registered together, and intratumor tracer uptake distributions were
      compared. Voxel-based Spearman correlation coefficients were used to quantify
      intertracer correlations, and the correlation coefficients of sarcomas and
      carcinomas were compared. The relative overlap of the highest uptake volumes of
      the 3 tracers was quantified, and the values were compared for sarcomas and
      carcinomas. RESULTS: Large degrees of heterogeneity in SUV measures and phenotype
      correlations were observed. Carcinoma and sarcoma tumors differed significantly
      in SUV measures, with carcinoma tumors having significantly higher (18)F-FDG
      maximum SUVs than sarcoma tumors (11.1 vs. 5.0; P = 0.01) as well as higher
      (61)Cu-ATSM mean SUVs (2.6 vs. 1.2; P = 0.02). Carcinomas had significantly
      higher population-averaged Spearman correlation coefficients than sarcomas in
      comparisons of (18)F-FDG and (18)F-FLT (0.80 vs. 0.61; P = 0.02), (18)F-FLT and
      (61)Cu-ATSM (0.83 vs. 0.38; P < 0.0001), and (18)F-FDG and (61)Cu-ATSM (0.82 vs.
      0.69; P = 0.04). Additionally, the highest uptake volumes of the 3 tracers had
      significantly greater overlap in carcinomas than in sarcomas. CONCLUSION: The
      relationships of glucose metabolism, proliferation, and hypoxia were
      heterogeneous across different tumors, with carcinomas tending to have high
      correlations and sarcomas having low correlations. Consequently, canine carcinoma
      tumors are robust targets for therapies that target a single biologic property,
      whereas sarcoma tumors may not be well suited for such therapies. Histology
      specific PET correlations have far-reaching implications for the robustness of
      biologic target definition.

PMID- 24042032
TI  - Sex-dependent neurochemical effects of environmental enrichment in the visual
      system.
AB  - Sex differences in the visual system have been reported in aspects of human
      vision, such as color perception, peripheral vision and even in the activation of
      the primary visual cortex. Similarly sex differences have been identified in the
      visual system of laboratory animals such as monkeys and rats. On the other hand,
      environmental enrichment (EE) has long been known to affect visual tissues.
      Taking into consideration the variation in the experimental approaches concerning
      EE and the sex differences in the visual system, we investigated in male and
      female rats the serotonergic and dopaminergic effects of EE in the retina and the
      visual cortex at different time points (i.e. P0-25, P0-P90 and P90-P150). Early
      EE in adulthood increased the serotonergic activity of the male visual cortex and
      the female retina (P0-P90). In addition early enrichment (P0-P90) increased
      dopaminergic activity in the female retina and in the visual cortex of both
      sexes. Late enrichment increased the serotonergic activity in the retina and
      visual cortex of both sexes (P90-P150), but increased the dopaminergic activity
      in the visual cortex only in male animals. In the present study we expose marked
      sex differences in the neurochemistry of visual tissues and we demonstrate for
      the first time that EE can in fact modify the serotonergic and dopaminergic
      neurotransmission in the retina and visual cortex. Overall, the present study
      underpins the sex-dependent neurochemical status of the visual system and
      provides insights into the different mechanisms underlying visual processing in
      the two sexes. 

PMID- 24042034
TI  - Compression injury in the mouse spinal cord elicits a specific proliferative
      response and distinct cell fate acquisition along rostro-caudal and dorso-ventral
      axes.
AB  - Harnessing the regenerative capabilities of endogenous precursor cells in the
      spinal cord may be a useful tool for clinical treatments aimed at replacing cells
      lost as a consequence of disease or trauma. To better understand the
      proliferative properties and differentiation potential of the adult spinal cord
      after injury, we used a mouse model of compression spinal cord injury (SCI).
      After injury, adult mice were administered BrdU to label mitotic cells and
      sacrificed at different time-points for immunohistochemical analysis. Our data
      show that the rate of proliferation increased in all regions of the spinal cord
      1day after injury, peaked after 3days, and remained elevated for at least 14days
      after injury. Proliferation was greater at the injury epicenter than in rostral
      and caudal adjacent spinal segments. The number of proliferative cells and rate
      of proliferation varied between dorsal and ventral regions of the spinal cord and
      between the gray and white matter. Newly generated cells expressed markers for
      progenitor cells (Nestin and Olig2), oligodendrocytes (Sox10), astrocytes (S100b
      and glial fibrillary acidic protein), and microglia (Iba1), but not neuronal
      markers (Map2 and NeuN). Marker expression varied with regard to the dorso
      ventral region, rostro-caudal proximity to the injury epicenter, and time after
      injury. At early time-points after injury, BrdU(+) cells mainly expressed
      microglial/macrophage and astrocytic markers, while at these same time-points in
      the control spinal cord the mitotic cells predominately expressed oligodendrocyte
      and oligodendrocyte progenitor cell markers. The profile of proliferation and
      cell fate marker expression indicates that after moderate compression, the spinal
      cord has the capacity to generate a variety of glial cells but not neurons, and
      that this pattern is space and time specific. Future studies should focus on ways
      to control proliferation and cell fate after injury to aid the development of
      cell replacement treatments for SCI. 

PMID- 24042035
TI  - Retrieval and reconsolidation of object recognition memory are independent
      processes in the perirhinal cortex.
AB  - Reconsolidation refers to the destabilization/re-stabilization process upon
      memory reactivation. However, the parameters needed to induce reconsolidation
      remain unclear. Here we evaluated the capacity of memory retrieval to induce
      reconsolidation of object recognition memory in rats. To assess whether retrieval
      is indispensable to trigger reconsolidation, we injected muscimol in the
      perirhinal cortex to block retrieval, and anisomycin (ani) to impede
      reconsolidation. We observed that ani impaired reconsolidation in the absence of
      retrieval. Therefore, stored memory underwent reconsolidation even though it was
      not recalled. These results indicate that retrieval and reconsolidation of object
      recognition memory are independent processes. 

PMID- 24042033
TI  - Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated
      in anti-nociceptive responses after experimental spinal cord injury.
AB  - Chronic neuropathic pain is a frequent comorbidity following spinal cord injury
      (SCI) and often fails to respond to conventional pain management strategies.
      Preventive administration of docosahexaenoic acid (DHA) or the consumption of a
      diet rich in omega-3 polyunsaturated fatty acids (O3PUFAs) confers potent
      prophylaxis against SCI and improves functional recovery. The present study
      examines whether this novel dietary strategy provides significant antinociceptive
      benefits in rats experiencing SCI-induced pain. Rats were fed control chow or
      chow enriched with O3PUFAs for 8weeks before being subjected to sham or cord
      contusion surgeries, continuing the same diets after surgery for another 8 more
      weeks. The paw sensitivity to noxious heat was quantified for at least 8weeks
      post-SCI using the Hargreaves test. We found that SCI rats consuming the
      preventive O3PUFA-enriched diet exhibited a significant reduction in thermal
      hyperalgesia compared to those consuming the normal diet. Functional
      neurometabolomic profiling revealed a distinctive deregulation in the metabolism
      of endocannabinoids (eCB) and related N-acyl ethanolamines (NAEs) at 8weeks post
      SCI. We found that O3PUFAs consumption led to a robust accumulation of novel NAE
      precursors, including the glycerophospho-containing docosahexaenoyl ethanolamine
      (DHEA), docosapentaenoyl ethanolamine (DPEA), and eicosapentaenoyl ethanolamine
      (EPEA). The tissue levels of these metabolites were significantly correlated with
      the antihyperalgesic phenotype. In addition, rats consuming the O3PUFA-rich diet
      showed reduced sprouting of nociceptive fibers containing CGRP and dorsal horn
      neuron p38 mitogen-activated protein kinase (MAPK) expression, well-established
      biomarkers of pain. The spinal cord levels of inositols were positively
      correlated with thermal hyperalgesia, supporting their role as biomarkers of
      chronic neuropathic pain. Notably, the O3PUFA-rich dietary intervention reduced
      the levels of these metabolites. Collectively, these results demonstrate the
      prophylactic value of dietary O3PUFA against SCI-mediated chronic pain. 

PMID- 24042036
TI  - Distinct activation profiles in microglia of different ages: a systematic study
      in isolated embryonic to aged microglial cultures.
AB  - Microglia have been implicated in disease progression for several age-related
      brain disorders. However, while microglia's contribution to the progression of
      these disorders is accepted, the effect of aging on their endogenous cellular
      characteristics has received limited attention. In fact, a comprehensive study of
      how the structure and function of microglia changes as a function of
      developmental age has yet to be performed. Here, we describe the functional
      response characteristics of primary microglial cultures prepared from embryonic,
      neonatal (Neo), 2-3month-old, 6-8month-old, 9-11month-old, and 13-15month-old
      rats. Microglial morphology, glutamate (GLU) uptake, and release of trophic and
      inflammatory factors were assessed under basal conditions and in microglia
      activated with adenosine 5'-triphosphate (ATP) or lipopolysaccharide. We found
      that microglia from different age groups were both morphologically and
      functionally distinct. Upon activation by ATP, Neo microglia were the most
      reactive, upregulating nitric oxide, tumor necrosis factor-alpha, and brain
      derived neurotrophic factor release as well as GLU uptake. This upregulation
      translated into neurotoxicity in microglia-neuron co-cultures that were not
      observed with microglia of different developmental ages. Interestingly, 13
      15month-old microglia exhibited similar activation profiles to Neo microglia,
      whereas microglia from younger adults and embryos were activated less by ATP. Our
      data also identify age-dependent differences in purinergic receptor subtype
      expression that contribute to the regulation of neuronal survival. Combined, our
      data demonstrate that microglial activation and purinergic receptor profiles vary
      non-linearly with developmental age, a potentially important finding for studies
      examining the role of microglia in neurodegenerative disorders. 

PMID- 24042037
TI  - In and out from the cortex: development of major forebrain connections.
AB  - In this review we discuss recent advances in the understanding of the development
      of forebrain projections attending to their origin, fate determination, and axon
      guidance. Major forebrain connections include callosal, corticospinal,
      corticothalamic and thalamocortical projections. Although distinct
      transcriptional programs specify these subpopulations of projecting neurons, the
      mechanisms involved in their axonal development are similar. Guidance by short-
      and long-range molecular cues, interaction with intermediate target populations
      and activity-dependent mechanisms contribute to their development. Moreover, some
      of these connections interact with each other showing that the development of
      these axonal tracts is a well-orchestrated event. Finally, we will recapitulate
      recent discoveries that challenge the field of neural wiring that show that these
      forebrain connections can be changed once formed. The field of reprogramming has
      arrived to postmitotic cortical neurons and has showed us that forebrain
      connectivity is not immutable and might be changed by manipulations in the
      transcriptional program of matured cells. 

PMID- 24042038
TI  - Activation of Mas oncogene-related gene (Mrg) C receptors enhances morphine
      induced analgesia through modulation of coupling of MU-opioid receptor to Gi
      protein in rat spinal dorsal horn.
AB  - Mas oncogene-related gene (Mrg) G protein-coupled receptors are exclusively
      expressed in small-sized neurons in trigeminal and dorsal root ganglia (DRG) in
      mammals. The present study investigated the effect of MrgC receptor activation on
      morphine analgesic potency and addressed its possible mechanisms. Intrathecal
      (i.t.) administration of the specific MrgC receptor agonist bovine adrenal
      medulla 8-22 (BAM8-22, 3 nmol) increased morphine-induced analgesia and shifted
      the morphine dose-response curve to the left in rats. Acute morphine (5 MUg)
      reduced the coupling of MU-opioid receptors (MORs) to Gi-, but not Gs-, protein
      in the spinal dorsal horn. The i.t. BAM8-22 (3 nmol) prevented this change of G
      protein repertoire while the inactive MrgC receptor agonist BAM8-18 (3 nmol,
      i.t.) failed to do so. A double labeling study showed the co-localization of MrgC
      and MORs in DRG neurons. The i.t. BAM8-22 also increased the coupling of MORs to
      Gi-protein and recruited Gi-protein from cytoplasm to the cell membrane in the
      spinal dorsal horn. Application of BAM8-22 (10nM) in the cultured ganglion
      explants for 30 min increased Gi-protein mRNA, but not Gs-protein mRNA. The
      present study demonstrated that acute administration of morphine inhibited the
      repertoire of MOR/Gi-protein coupling in the spinal dorsal horn in vivo. The
      findings highlight a novel mechanism by which the activation of MrgC receptors
      can modulate the coupling of MORs with Gi-protein to enhance morphine-induced
      analgesia. Hence, adjunct treatment of MrgC agonist BAM8-22 may be of therapeutic
      value to relieve pain.

PMID- 24042039
TI  - Effects of acute intermittent hypoxia on energy balance and hypothalamic feeding
      pathways.
AB  - This study was done to investigate the effects of acute intermittent hypoxia (IH)
      on metabolic factors associated with energy balance and body weight, and on
      hypothalamic satiety-inducing pathways. Adult male Sprague-Dawley rats were
      exposed to either 8h IH or normoxic control conditions. Food intake, locomotion
      and body weights were examined after IH. Additionally, plasma levels of leptin,
      adiponectin corticosterone, insulin and blood glucose were measured following
      exposure to IH. Furthermore, adipose tissue was removed and analyzed for leptin
      and adiponectin content. Finally, the hypothalamic arcuate nucleus (ARC) was
      assessed for alterations in protein signaling associated with satiety. IH reduced
      body weight, food intake and active cycle locomotion without altering adipose
      tissue mass. Leptin protein content was reduced while adiponectin content was
      elevated in adipose tissue after IH. Plasma concentration of leptin was
      significantly increased while adiponectin decreased after IH. No changes were
      found in plasma corticosterone, insulin and blood glucose. In ARC,
      phosphorylation of signal transducer and activator of transcription-3 and pro
      opiomelanocortin (POMC) expression were elevated. In addition, POMC-expressing
      neurons were activated as determined by immediate early gene FRA-1/2 expression.
      Finally, ERK1/2 and its phosphorylation were reduced in response to IH. These
      data suggest that IH induces significant alterations to body energy balance
      through changes in the secretion of leptin which exert effects on satiety
      inducing pathways within the hypothalamus. 

PMID- 24042040
TI  - Investigating univariate temporal patterns for intrinsic connectivity networks
      based on complexity and low-frequency oscillation: a test-retest reliability
      study.
AB  - Intrinsic connectivity networks (ICNs) are composed of spatial components and
      time courses. The spatial components of ICNs were discovered with moderate-to
      high reliability. So far as we know, few studies focused on the reliability of
      the temporal patterns for ICNs based their individual time courses. The goals of
      this study were twofold: to investigate the test-retest reliability of temporal
      patterns for ICNs, and to analyze these informative univariate metrics.
      Additionally, a correlation analysis was performed to enhance interpretability.
      Our study included three datasets: (a) short- and long-term scans, (b) multi-band
      echo-planar imaging (mEPI), and (c) eyes open or closed. Using dual regression,
      we obtained the time courses of ICNs for each subject. To produce temporal
      patterns for ICNs, we applied two categories of univariate metrics: network-wise
      complexity and network-wise low-frequency oscillation. Furthermore, we validated
      the test-retest reliability for each metric. The network-wise temporal patterns
      for most ICNs (especially for default mode network, DMN) exhibited moderate-to
      high reliability and reproducibility under different scan conditions. Network
      wise complexity for DMN exhibited fair reliability (ICC<0.5) based on eyes-closed
      sessions. Specially, our results supported that mEPI could be a useful method
      with high reliability and reproducibility. In addition, these temporal patterns
      were with physiological meanings, and certain temporal patterns were correlated
      to the node strength of the corresponding ICN. Overall, network-wise temporal
      patterns of ICNs were reliable and informative and could be complementary to
      spatial patterns of ICNs for further study. 

PMID- 24042042
TI  - [Predictors of poor self-rated health in an elderly population].
AB  - INTRODUCTION: Self-Rated Health is part of the comprehensive concept of Quality
      of Life and is a valid measurement of health status. The main objective of this
      study was to test the predictive value of some different variables on the poor
      Self-Rated Health among elders. MATERIAL AND METHODS: We performed a cross
      sectional study on a sample consisting of 140 participants. MEASUREMENTS: age,
      gender, level of education, environment, cognitive status, physical impairment,
      diseases, health perception and social support. The influence of the studied
      variables on the poor Self-Rated Health was performed with a logistic regression
      analysis and a ROC curve to establish the cut-off values for these variables with
      the best sensitivity and specificity to predict the poor Self-Rated Health.
      RESULTS: A poor Self-Rated Health was significantly associated with age,
      comorbidity, and the perception of poor functional social support, whereas no
      association was found with gender, environment and educational level.
      CONCLUSIONS: Old age, the number of diagnosed diseases, and functional social
      support are Self-Rated Health risk factors, while the characteristics and
      repercussions of the diseases should not be considered.

PMID- 24042041
TI  - Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal
      fluid.
AB  - Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate
      many important physiological functions. Ghrelin receptor, named the growth
      hormone secretagogue receptor (GHSR), is present in many brain areas with or
      without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin
      is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF
      ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin
      present in the CSF. For this purpose, we centrally injected mice with fluorescein
      labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the
      distribution of F-ghrelin signal through the brain. Our results indicated that
      centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR
      is present. Also, we detected F-ghrelin uptake in the ependymal cells of both
      wild-type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most
      of brain areas expressing GHSR. Also, we propose that the accessibility of CSF
      ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR
      independent manner. 

PMID- 24042043
TI  - [Diabetic nephropathy confirmed by renal biopsy: are there age differences?].

PMID- 24042044
TI  - Biological activity of neutral and cationic iridium(III) complexes with kappaP
      and kappaP,kappaS coordinated Ph2PCH2S(O)xPh (x = 0-2) ligands.
AB  - Neutral iridium(III) complexes of the type [Ir(eta(5)-C5Me5)Cl2{Ph2PCH2S(O)xPh
      kappaP}] (1-3) with diphenylphosphino-functionalized methyl phenyl sulfides,
      sulfoxides, and sulfones Ph2PCH2S(O)xPh (x = 0, L1; 1, L2; 2, L3) and the
      cationic complex [Ir(eta(5)-C5Me5)Cl{Ph2PCH2SPh-kappaP,kappaS}][PF6] (4) were
      synthesized and fully characterized analytically and spectroscopically.
      Furthermore, the structure of 2 was determined by X-ray diffraction analysis. The
      biological potential of the neutral and cationic iridium(III) complexes was
      tested in vitro against the cell lines 8505C, A253, MCF-7, SW480 and 518A2.
      Complex [Ir(eta(5)-C5Me5)Cl2{Ph2PCH2S(O)Ph-kappaP}] (2), with ligand L2 kappaP
      coordinated containing a pendent sulfinyl group, is the most active one (IC50
      values of about 3 MUM), thus, with activities comparable to cisplatin. Complex 2
      proved to have an even a higher antiproliferative activity than cisplatin against
      8505C and SW480 cell lines, used as a model system of highly anaplastic cancers
      with low sensitivity to conventional chemotherapeutics such as cisplatin.
      Additional experiments demonstrated that apoptosis and autophagic cell death
      contribute to the drug's tumoricidal action.

PMID- 24042045
TI  - Preparation and biological evaluation of 99mTc-N4IPA for single photon emission
      computerized tomography imaging of hypoxia in mouse tumor.
AB  - In order to develop technetium-99m labeled nitroimidazole imaging agent for
      hypoxia in tumor, we have synthesized (99m)Tc-1-(4-nitroimidazole-yl)
      propanhydroxyiminoamide, (99m)Tc-N4IPA complex, in high radiochemical purity and
      radiochemical yield. The biological evaluation of this complex includes the in
      vitro/vivo stability, cell uptake and Single Photon Emission Computerized
      Tomography (SPECT) imaging in mouse tumor models, respectively. These results
      demonstrate that (99m)Tc-N4IPA may have potential as clinical hypoxia imaging
      agent. The key features of the biological evaluation include the following: (1)
      the autoradiogram of (99m)Tc-N4IPA complex in tissue samples of hypoxia overlaps
      with the area stained by hypoxyprobe-1; (2) SPECT imaging of U87-bearing mice
      clearly identifies tumors 4 h post injection of (99m)Tc-N4IPA, reaching ID% of
      8.48 +/- 4.51; (3) the main pathways of excretion of (99m)Tc-N4IPA are through
      kidneys and livers in both A549 or U87-bearing tumor mice.

PMID- 24042046
TI  - Sentinel and nonsentinel lymph node assessment using a combination of one-step
      nucleic acid amplification and conventional histological examination.
AB  - BACKGROUND: Clinical significance of intraoperative sentinel lymph node (SLN)
      metastases detection using one-step nucleic acid amplification (OSNA) has not
      been thoroughly investigated. The aim of this study was to assess the usefulness
      of using a combination of OSNA and conventional histological examinations.
      MATERIALS AND METHODS: We included 772 consecutive patients with clinical node
      negative cTis-cT3 primary breast cancer who underwent SLN biopsy with
      intraoperative OSNA and multi-section histological examination at our
      institution. We estimated the concordance rate and compared SLN metastases
      detection rates between the two methods. We also compared non-SLN metastasis
      detection rate between patients who tested positive in OSNA and those who tested
      positive in histology. RESULTS: Among 772 patients, SLN metastases were
      intraoperatively detected in 211 (26.4%) by either OSNA or histology, in 168
      (21.8%) by OSNA, and in 150 (19.4%) by histology. The concordance rate between
      OSNA and histological examination was 89.2%, but only 123 (58.8%) patients tested
      positive in both OSNA and histology; 45 were positive in OSNA only and 43 were
      positive in histology only. SLN status as per both OSNA and histology was
      significantly correlated with the presence of non-SLN metastases and multivariate
      analysis-identified independent predictive factors of non-SLN metastases.
      CONCLUSIONS: Intraoperative SLN metastases detection may be more accurate with a
      combination of OSNA and histological examination than with OSNA or histological
      examination alone. By using both methods, we can reduce the risk of false
      negative rate in SLN biopsy, and may prevent physicians from overlooking patients
      with non-SLN metastases.

PMID- 24042047
TI  - [Hepatitis B: cross-sectional study of knowledge and immunization among students
      at University of Cocody, Ivory Coast].
AB  - BACKGROUND: To evaluate knowledge about hepatitis B and vaccination coverage
      among students at Cocody's University, Ivory Coast. MATERIALS AND METHODS: A
      cross-sectional study was conducted during the academic year 2005-2006 (2557
      students). Parameters were collected by interview using a survey chart. Factors
      influencing knowledge and vaccination against hepatitis B were analyzed by
      logistic regression. RESULTS: The majority of students (n=1174, 69.4% [95% CI 68
      71]) knew about hepatitis B. Only 17.5% and 26.1% of students respectively were
      aware of sexual and blood transmission. None of the students were aware of
      maternal-fetal transmission. Factors associated with knowledge of hepatitis B
      were enrollment in health sciences (Odds Ratio=24.19 [95% CI 8.65-76.63]) and
      having a scholarship (Odds Ratio=2.34 [95% CI 1.54-3.56]). Vaccination coverage
      against hepatitis B was low (Odds Ratio=3.7% [95% CI 3-4]). Factors associated
      with vaccination were: knowledge of hepatitis B (Odds Ratio=6.83 [95% CI 4.57
      10.27]), enrollment in health sciences (Odds Ratio=3.59 [95% CI 2.60-4.96]),
      marriage (Odds Ratio=2.04 [95% CI 1.13-3.64]) and having a scholarship (Odds
      Ratio=1.60 [95% CI 1.09-2.35]). CONCLUSION: Knowledge and vaccination coverage
      against hepatitis B among students at Cocody's University is low. Students should
      be given information about hepatitis B and access to free vaccination. Students
      enrolled in health sciences should be vaccinated before admission because of
      specific risks of contamination, for themselves and for their patients.

PMID- 24042048
TI  - New quantitative methods for measuring plasmid loss rates reveal unexpected
      stability.
AB  - Plasmid loss rate measurements are standard in microbiology and key to
      understanding plasmid stabilization mechanisms. The conventional assays eliminate
      selection for plasmids at the beginning of the experiment and screen for the
      appearance of plasmid-free cells over long-term population growth. However, it
      has been long appreciated in plasmid biology that the growth rate differential
      between plasmid-free and plasmid-containing cells at some point overshadows the
      effect of primary loss events, such that the assays can greatly over-estimate
      inherent loss rates. The standard solutions to this problem are to either
      consider the very early phase of loss where the fraction of plasmid-free cells
      increases linearly, or to measure the growth rate difference either by following
      the population for longer time or by measuring growth rates separately. Here we
      mathematically show that in all these cases, seemingly small experimental errors
      in the growth rate estimates can overshadow the estimates of the loss rates. For
      many plasmids, loss rates may thus be much lower than previously thought, and for
      some plasmids, the estimated loss rate may have nothing to do with actual loss
      rates. We further modify two independent experimental methods to separate
      inherent losses from growth differences and apply them to the same plasmids.
      First we use a high-throughput microscopy-based approach to screen for plasmid
      free cells at extremely short time scales--tens of minutes rather than tens of
      generations--and apply it to a par- version of mini-R1. Second we modify a
      counterselection-based plasmid loss assay inspired by the Luria-Delbruck
      fluctuation test that completely separates losses from growth, and apply it to
      various R1 and pSC101 derivatives. Concordant results from the two assays suggest
      that plasmids are lost at a lower frequency than previously believed. In fact,
      for par- mini-R1 the observed loss rate of about 10-3 per cell and generation
      seems to be so low as to be inconsistent with what we know about the R1
      stabilization mechanisms, suggesting these well characterized plasmids may have
      some additional and so far unknown stabilization mechanisms, for example
      improving copy number control or partitioning at cell division.

PMID- 24042049
TI  - The phage integrase vector pIPI03 allows RecA-independent, site-specific
      labelling of Staphylococcus lugdunensis strains.
AB  - Staphylococcus lugdunensis is a coagulase negative staphylococcus that is a
      commensal of man and an opportunistic pathogen. A site-specific integrative
      plasmid for the use in S. lugdunensis was constructed and validated. The
      integrase gene ccrB of bacteriophage phiSL01 together with its attachment site
      was cloned into the thermosensitive plasmid pIMAY. The resulting plasmid pIPI03
      integrated RecA-independently, site-specifically and irreversibly into the S.
      lugdunensis chromosome. Two IPTG-inducible antibiotic resistance determinants
      were cloned into pIPI03 and the derivatives were used to construct strains
      suitable for competitive growth experiments in both in vitro and in vivo. 

PMID- 24042050
TI  - Subcellular localization of the pyoverdine biogenesis machinery of Pseudomonas
      aeruginosa: a membrane-associated "siderosome".
AB  - The peptidic siderophore pyoverdine is the primary iron uptake system of
      fluorescent pseudomonads, and a virulence factor in the opportunistic pathogen
      Pseudomonas aeruginosa. Pyoverdine biogenesis is a co-ordinate process requiring
      several precursor-generating enzymes and large nonribosomal peptide synthetases
      (NRPSs) in the cytoplasm, followed by extracytoplasmic maturation. By using cell
      fractionation, protein-protein interaction, and in vivo labeling assays we
      obtained evidence that, in P. aeruginosa, pyoverdine NRPSs assemble with
      precursor-generating enzymes into a membrane-bound multi-enzymatic complex, for
      which we propose the name "siderosome". The pyoverdine biogenetic complex
      represents a novel example of subcellular compartmentalization of a secondary
      metabolic pathway in prokaryotes. 

PMID- 24042051
TI  - Coronary heart disease alters intercellular communication by modifying
      microparticle-mediated microRNA transport.
AB  - Coronary heart disease (CHD) is characterized by abnormal intercellular
      communication and circulating microRNAs (miRNAs) are likely involved in this
      process. Here, we show that CHD was associated with changes in the transport of
      circulating miRNA, particularly decreased miRNA enrichment in microparticles
      (MPs). Additionally, MPs from CHD patients were less efficient at transferring
      miRNA to cultured HUVECs, which correlated with their diminished capacity to bind
      developmental endothelial locus-1 (Del-1). In summary, CHD was associated with
      distinct changes in circulating miRNA transport and these changes may contribute
      to the abnormal intercellular communication that underlies CHD initiation and
      progression. 

PMID- 24042053
TI  - Analysis of characterizing phases on waveform: an application to vertical jumps.
AB  - The aim of this study is to propose a novel data analysis approach, an analysis
      of characterizing phases (ACP), that detects and examines phases of variance
      within a sample of curves utilizing the time, magnitude, and magnitude-time
      domains; and to compare the findings of ACP to discrete point analysis in
      identifying performance-related factors in vertical jumps. Twenty-five vertical
      jumps were analyzed. Discrete point analysis identified the initial-to-maximum
      rate of force development (P=.006) and the time from initial-to-maximum force
      (P=.047) as performance-related factors. However, due to intersubject variability
      in the shape of the force curves (ie, non-, uni- and bimodal nature), these
      variables were judged to be functionally erroneous. In contrast, ACP identified
      the ability to apply forces for longer (P<.038), generate higher forces (P<.027),
      and produce a greater rate of force development (P<.003) as performance-related
      factors. Analysis of characterizing phases showed advantages over discrete point
      analysis in identifying performance-related factors because it (i) analyses only
      related phases, (ii) analyses the whole data set, (iii) can identify performance
      related factors that occur solely as a phase, (iv) identifies the specific phase
      over which differences occur, and (v) analyses the time, magnitude and combined
      magnitude-time domains.

PMID- 24042052
TI  - Blockade of islet amyloid polypeptide fibrillation and cytotoxicity by the
      secretory chaperones 7B2 and proSAAS.
AB  - The deposition of fibrillated human islet beta-cell peptide islet amyloid
      polypeptide (hIAPP) into amyloid plaques is characteristic of the pathogenesis of
      islet cell death during type 2 diabetes. We investigated the effects of the
      neuroendocrine secretory proteins 7B2 and proSAAS on hIAPP fibrillation in vitro
      and on cytotoxicity. In vitro, 21-kDa 7B2 and proSAAS blocked hIAPP fibrillation.
      Structure-function studies showed that a central region within 21-kDa 7B2 is
      important in this effect and revealed the importance of the N-terminal region of
      proSAAS. Both chaperones blocked the cytotoxic effects of exogenous hIAPP on
      Rin5f cells; 7B2 generated by overexpression was also effective. ProSAAS and 7B2
      may perform a chaperone role as secretory anti-aggregants in normal islet cell
      function and in type 2 diabetes. 

PMID- 24042054
TI  - Risk of suicide in male prison inmates.
AB  - AIMS: Many studies have demonstrated that the risk of suicide in prison is higher
      than in the general population. This study has two aims. First, to explore the
      risk of suicide in men sentenced in Andalusian prisons. And second, to study the
      sociodemographic, criminal and, especially, psychopathological factors associated
      with this risk. METHODS: An assessment was made of 472 sentenced inmates in two
      Andalusian prisons, and included a sociodemographic interview, the IPDE
      personality disorders questionnaire, the SCID-I diagnostic interview (DSMIV), and
      the Plutchick suicide risk questionnaire. The interviewers were experienced
      clinical psychologists with training in prison environments. Adjusted ORs were
      calculated using a logistic regression. RESULTS: A risk of committing suicide was
      detected in 33.5% of the sample. The diagnoses (lifetime prevalence) of affective
      disorder (adjusted OR 3329), substance dependence disorders (adjusted OR 2733),
      personality disorders (adjusted OR 3115) and anxiety disorder (adjusted OR 1650),
      as well as a family psychiatric history (adjusted OR 1650), were the predictors
      that remained as risk factors after the regression analysis. No socio-demographic
      risk factor was significant in the regression analysis. CONCLUSIONS: The
      psychopathological variables are essential and the most powerful factors to
      explain suicide risk in prisons. A correct and systematic diagnosis, and an
      appropriate treatment by mental health professionals during the imprisonment are
      essential to prevent the risk of suicide.

PMID- 24042055
TI  - Basal cell carcinoma of the nipple-areola complex: report of a case and
      literature review.
AB  - Basal cell carcinoma of the nipple areola complex in female patients is an
      extremely rare tumor with a malignant clinical behavior. The Authors present the
      case of a Basal cell carcinoma of the nipple areola complex in a Caucasian woman,
      evaluated by clinical and histological findings. Our clinical experience suggests
      that Basal cell carcinoma of the nipple areola complex has a local aggressive
      behavior with an higher metastatic potentiality compared to basal cell carcinoma
      of common sites. However, an accurate tissue sparing excision may be successful
      in the long term.

PMID- 24042056
TI  - In vivo imaging in NHP models of malaria: challenges, progress and outlooks.
AB  - Animal models of malaria, mainly mice, have made a large contribution to our
      knowledge of host-pathogen interactions and immune responses, and to drug and
      vaccine design. Non-human primate (NHP) models for malaria are admittedly under
      used, although they are probably closer models than mice for human malaria; in
      particular, NHP models allow the use of human pathogens (Plasmodium falciparum,
      Plasmodium vivax, Plasmodium malariae and Plasmodium knowlesi). NHPs, whether
      natural hosts or experimentally challenged with a simian Plasmodium, can also
      serve as robust pre-clinical models. Some simian parasites are closely related to
      a human counterpart, with which they may share a common ancestor, and display
      similar major features with the human infection and pathology. NHP models allow
      longitudinal studies, from the early events following sporozoite inoculation to
      the later events, including analysis of organs and tissues, particularly liver,
      spleen, brain and bone marrow. NHP models have one other significant advantage
      over mouse models: NHPs are our closest relatives and thus their biology is very
      similar to ours. Recently developed in vivo imaging tools have provided insight
      into malaria parasite infection and disease in mouse models. One advantage of
      these tools is that they limit the need for invasive procedures, such as tissue
      biopsies. Many such technologies are now available for NHP studies and provide
      new opportunities for elucidating host/parasite interactions. The aim of this
      review is to bring the malaria community up to date on what is currently possible
      and what soon will be, in terms of in vivo imaging in NHP models of malaria, to
      consider the pros and the cons of the various techniques, and to identify
      challenges. 

PMID- 24042057
TI  - Capillaria plica (syn. Pearsonema plica) infection in a dog with chronic
      pollakiuria: challenges in the diagnosis and treatment.
AB  - Capillaria plica (syn. Pearsonema plica) is a nematode parasite of the urinary
      tract of canids, felids and mustelids, which can cause cystitis, pollakiuria,
      dysuria and hematuria. An eight-month-old female crossbred dog from Switzerland
      presented a six-month history of frequent urination. During the first clinical
      examination, C. plica eggs were detected in the urine sediment. Three series of
      treatments with fenbendazole (50 mg/kg body weight[BW]/day, orally) for 10 days
      each, three single day treatments with moxidectin-imidacloprid (spot-on) and one
      single administration of ivermectin (0.2 mg/kg BW subcutaneously) were performed
      within an eight-month period. None of those treatments succeeded in eliminating
      the C. plica infection or in resolving the clinical signs. An endoscopic
      examination of the urine bladder still revealed numerous adult viable C. plica
      worms attached to the bladder mucosa. A two-day treatment with levamisole (7.5
      mg/kg BW/day intramuscularly) was subsequently performed. An endoscopic control
      of the urine bladder two days after this treatment and a urine analysis after two
      weeks confirmed the elimination of the parasites. The clinical signs disappeared
      within one month. Levamisole was shown to be effective against C. plica infection
      in a dog, whereas previous treatments with fenbendazole, moxidectin and
      ivermectin had failed.

PMID- 24042058
TI  - Diversity of Babesia bovis merozoite surface antigen genes in the Philippines.
AB  - Babesia bovis is the causative agent of fatal babesiosis in cattle. In the
      present study, we investigated the genetic diversity of B. bovis among Philippine
      cattle, based on the genes that encode merozoite surface antigens (MSAs). Forty
      one B. bovis-positive blood DNA samples from cattle were used to amplify the msa
      1, msa-2b, and msa-2c genes. In phylogenetic analyses, the msa-1, msa-2b, and msa
      2c gene sequences generated from Philippine B. bovis-positive DNA samples were
      found in six, three, and four different clades, respectively. All of the msa-1
      and most of the msa-2b sequences were found in clades that were formed only by
      Philippine msa sequences in the respective phylograms. While all the msa-1
      sequences from the Philippines showed similarity to those formed by Australian
      msa-1 sequences, the msa-2b sequences showed similarity to either Australian or
      Mexican msa-2b sequences. In contrast, msa-2c sequences from the Philippines were
      distributed across all the clades of the phylogram, although one clade was formed
      exclusively by Philippine msa-2c sequences. Similarities among the deduced amino
      acid sequences of MSA-1, MSA-2b, and MSA-2c from the Philippines were 62.2-100,
      73.1-100, and 67.3-100%, respectively. The present findings demonstrate that B.
      bovis populations are genetically diverse in the Philippines. This information
      will provide a good foundation for the future design and implementation of
      improved immunological preventive methodologies against bovine babesiosis in the
      Philippines. The study has also generated a set of data that will be useful for
      futher understanding of the global genetic diversity of this important parasite. 

PMID- 24042059
TI  - Activation of anaerobic metabolism in Biomphalaria glabrata (Mollusca:
      Gastropoda) experimentally infected by Angiostrongylus cantonensis (Nematoda,
      Metastrongylidae) by high-performance liquid chromatography.
AB  - The activity of lactate dehydrogenase and the concentrations of glucose in the
      hemolymph and of glycogen in the digestive gland and cephalopedal mass of
      Biomphalaria glabrata experimentally infected with Angiostrongylus cantonensis
      were evaluated. Additionally, high performance liquid chromatography (HPLC) was
      used to determine the hemolymph concentrations of some carboxylic acids (oxalic,
      piruvic, lactic and succinic). After one, two and three weeks of infection, the
      snails were dissected to collect the hemolymph and separate the tissues. A
      significant reduction of the levels of glucose in the hemolymph was observed as
      of the first week of infection in relation to the control group. The lactate
      dehydrogenase activity of the infected group was significantly higher than the
      average of the control group. This increase was accompanied by a reduction of the
      levels of piruvic acid and an increase in the levels of lactic acid in the
      hemolymph of the parasited snails, confirming the acceleration of the anaerobic
      metabolism, necessary for the host to obtain energy and maintain its redox
      balance. In parallel, there was a decrease in the glycogen content of the storage
      tissues, with that reduction being significantly greater in the cephalopedal mass
      than the digestive gland, demonstrating that in this interaction system, the
      mobilization of glycogen was not sufficient to maintain and reestablish the
      normal glycemia of the infected snails. 

PMID- 24042060
TI  - Diversity of sea lice (Copepoda: Caligidae) parasitic on marine fishes with
      commercial and aquaculture importance in Chamela Bay, Pacific coast of Mexico by
      using morphology and DNA barcoding, with description of a new species of Caligus.
AB  - The occurrence of parasitic copepods of the family Caligidae on wild and cultured
      marine fishes from Chamela Bay, on the Pacific coast of Mexico, is reported. A
      total of 16 species of Caligus and 1 species of Lepeophtheirus were found on 19
      wild fish species. The description of Caligus chamelensis n. sp. parasitizing
      Kyphosus elegans is presented. Among the species of Caligus reported here,
      Caligus serratus is the most common since it was found infecting 11 fish species.
      On cultured fish, Lutjanus gutattus and L. peru, only one species of Caligus, C.
      sclerotinosus was collected. DNA barcodes [mitochondrial cytochrome c oxidase
      subunit I (COI) gene sequences] were obtained for the majority of the sea lice
      species herein reported. The molecular analyses support the recognition of the
      new species and suggest that neither Caligus nor Lepeophtheirus are monophyletic.
      COI is shown to be a good candidate for parasitic copepod species identification,
      although a more robust reference database is needed to expand our ability to
      accomplish a molecular identification. 

PMID- 24042061
TI  - Changing medical culture to promote physical activity in secondary prevention of
      coronary artery disease.

PMID- 24042062
TI  - Drug-induced valve disease and considerations of benefit versus risk.

PMID- 24042063
TI  - Isolation and structure elucidation of linolipins C and D, complex oxylipins from
      flax leaves.
AB  - Two complex oxylipins (linolipins C and D) were isolated from the leaves of flax
      plants inoculated with phytopathogenic bacteria Pectobacterium atrosepticum.
      Their structures were elucidated based on UV, MS and NMR spectroscopic data. Both
      oxylipins were identified as digalactosyldiacylglycerol (DGDG) molecular species.
      Linolipin C contains one residue of divinyl ether (omega5Z)-etherolenic acid and
      one alpha-linolenate residue at sn-1 and sn-2 positions, respectively. Linolipin
      D possesses two (omega5Z)-etherolenic acid residues at both sn-1 and sn-2
      positions. The rapid formation (2-30min) of linolipins C and D alongside with
      linolipins A and B occurred in the flax leaves upon their damage by freezing
      thawing. 

PMID- 24042064
TI  - Anti-inflammatory phenanthrene derivatives from stems of Dendrobium denneanum.
AB  - Cultivated Dendrobium denneanum has been substituted for other endangered
      Dendrobium species in recent years, but there have been few studies regarding
      either its chemical constituents or pharmacological effects. In this study, three
      phenanthrene glycosides, three 9,10-dihydrophenanthrenes, two 9,10
      dihydrophenanthrenes glycosides, and four known phenanthrene derivatives, were
      isolated from the stems of D. denneanum. Their structures were elucidated on the
      basis of MS and NMR spectroscopic data. Ten compounds were found to inhibit
      nitric oxide (NO) production in lipopolysaccharide (LPS)-activated mouse
      macrophage RAW264.7 cells with IC50 values of 0.7-41.5 MUM, and exhibited no
      cytotoxicity in RAW264.7, HeLa, or HepG2 cells. Additionally, it was found that
      2,5-dihydroxy-4-methoxy-phenanthrene 2-O-beta-d-glucopyranoside, and 5-methoxy
      2,4,7,9S-tetrahydroxy-9,10-dihydrophenanthrene suppressed LPS-induced expression
      of inducible NO synthase (iNOS) inhibited phosphorylation of p38, JNK as well as
      mitogen-activated protein kinase (MAPK), and inhibitory kappa B-alpha
      (IkappaBalpha). This indicated that both compounds exert anti-inflammatory
      effects by inhibiting MAPKs and nuclear factor kappaB (NF-kappaB) pathways.

PMID- 24042065
TI  - Bilateral first branchial cleft anomaly with evidence of a genetic aetiology.
AB  - Anomalies of the first branchial cleft (FBC) are uncommon, and recognizing them
      can be difficult. Although present at birth, many cases do not become evident
      until later in childhood or adolescence, with an initial clinical presentation in
      adulthood being encountered only rarely. Typically, FBC anomalies present as a
      unilateral cyst, sinus, or fistula associated with the external auditory canal,
      or with swelling or an inflammatory opening in the peri-auricular/parotid area.
      They are commonly misdiagnosed and are often treated inadequately before being
      excised completely. A 40-year-old woman presented to the maxillofacial outpatient
      clinic with an episode of bilateral pre-auricular tumefaction, initially
      diagnosed as temporomandibular dysfunction syndrome. This was associated with
      bilateral pre-auricular pain that increased with mandibular movements. In
      relation to the patient's history, and given the bilateral presence of a pre
      auricular pit, a diagnosis of FBC anomaly was made. Further investigation showed
      a related asymptomatic history in five other cases across four generations of the
      same family. The authors describe here the case, the diagnostic methodology, and
      the wide local excision technique used for removal of the branchial sinus. 

PMID- 24042067
TI  - Segment tilting associated with surgically assisted rapid maxillary expansion.
AB  - This study aimed to evaluate, via computed tomography, the direction and
      magnitude of the segmental tilting that may occur after surgically assisted rapid
      maxillary expansion (SARME) in patients with a transverse maxillary deficiency.
      Thirty adult patients with a transverse maxillary deficiency greater than 5mm
      were treated by SARME. The procedures consisted of bilateral zygomatic buttress
      and midpalatal osteotomies combined with the use of a tooth-borne orthopaedic
      device postoperatively. Axial and coronal images were obtained before and 6
      months after SARME to evaluate the segment tilting. The greatest expansion
      occurred in the most inferior (5.4 +/- 1.1 mm) and anterior (4.0 +/- 1.3 mm)
      regions of the maxilla. The expanded segment tilted outward inferiorly and
      anteriorly in coronal and axial images, respectively. The segment tilting was 2.0
      mm (2.3%) inferiorly and 3.1mm (12.8%) anteriorly. It can be concluded that an
      outward tilting occurs in the most inferior and anterior portions of the maxilla
      during SARME procedures. Hence the direction and magnitude of such segmental
      tilting must be considered preoperatively when determining the surgical
      objectives.

PMID- 24042066
TI  - Analgesic efficacy of lysine clonixinate plus tramadol versus tramadol in
      multiple doses following impacted third molar surgery.
AB  - This study compared the analgesic and anti-inflammatory efficacy, trismus
      control, and tolerability of the combination of lysine clonixinate and tramadol
      (LCT) versus tramadol (T) alone after surgical removal of impacted mandibular
      third molars. This study was a double-blind, randomized clinical trial, including
      two study groups of 20 patients each, who exhibited acute pain subsequent to
      surgical extraction of two mandibular third molars. Pain intensity was quantified
      over a 96-h period using a visual analogue scale and a 5-point verbal rating
      scale. Secondary indicators of analgesic and anti-inflammatory efficacy, trismus
      control, and tolerability were determined. Patients administered LCT exhibited
      better therapeutic effects that those administered T. Fifty percent of patients
      in the LCT group rated this therapy as 'excellent analgesia' compared with only
      10% in the T group. The onset of the analgesic effect of LCT was significantly
      faster, without any therapeutic failures. There were no significant differences
      between the groups with regard to anti-inflammatory effect or trismus. The
      results of this study suggest that the postsurgical analgesic efficacy of LCT in
      combination (LC 125 mg + T 25 mg) is superior to that obtained with T alone,
      administered at the standard dose of 50 mg, for up to 96 h after the extraction
      of both impacted mandibular third molars.

PMID- 24042069
TI  - Premonitory Urges in Adults With Complicated and Uncomplicated Tourette Syndrome.
AB  - Most patients with Tourette syndrome (TS) report experiencing subjective bodily
      sensations termed premonitory urges, before they have a tic. This study
      investigated relationships between premonitory urges and tic severity,
      depression, anxiety, obsessions, compulsions, and attention problems. We also
      explored possible differences between patients with and without comorbid
      conditions. Finally, we explored whether premonitory urges impacted on perceived
      quality of life (QoL). One hundred adult outpatients (70 males; mean age 32
      years) were recruited from a specialist TS clinic. Fifty percent exhibited
      comorbid diagnoses, the most common of which were obsessive-compulsive disorder
      (23%), attention-deficit hyperactivity disorder (15%), anxiety (6%), and
      depression (5%). For the entire sample, premonitory urges were significantly
      related to clinical symptoms, especially obsessive-compulsive symptoms and
      anxiety, and were significantly negatively related to QoL scores. Premonitory
      urges had a strong negative correlation with QoL in patients with "pure" TS (no
      comorbidities), while this relationship was weaker for patients with comorbid
      conditions, who reported stronger or more frequent premonitory urges in
      association with greater anxiety. These findings may imply that slightly
      different psychological factors drive self-reported premonitory urge ratings in
      patients with and without comorbidities and that the perceived influence of
      distressing premonitory urges on wellbeing is less important in the context of
      comorbid symptomatology. As premonitory urges are related to QoL, they should be
      taken into account during evaluation of treatment efficacy, especially in cases
      with "pure" TS. 

PMID- 24042068
TI  - Effects of four treatment strategies for temporomandibular joint closed lock.
AB  - A previous randomized controlled trial (RCT) by Schiffman et al. (2007)(15)
      compared four treatments strategies for temporomandibular joint (TMJ) disc
      displacement without reduction with limited mouth opening (closed lock). In this
      parallel group RCT, 106 patients with magnetic resonance imaging (MRI)-confirmed
      TMJ closed lock were randomized between medical management, non-surgical
      rehabilitation, arthroscopic surgery, and arthroplasty. Surgical groups also
      received rehabilitation post-surgically. The current paper reassesses the
      effectiveness of these four treatment strategies using outcome measures
      recommended by the International Association of Oral and Maxillofacial Surgeons
      (IAOMS). Clinical assessments at baseline and at follow-up (3, 6, 12, 18, 24, and
      60 months) included intensity and frequency of TMJ pain, mandibular range of
      motion, TMJ sounds, and impairment of chewing. TMJ MRIs were performed at
      baseline and 24 months, and TMJ tomograms at baseline, 24 and 60 months. Most
      IAOMS recommended outcome measures improved significantly over time (P<=0.0003).
      There was no difference between treatment strategies relative to any treatment
      outcome at any follow-up (P>=0.16). Patient self-assessment of treatment success
      correlated with their ability to eat, with pain-free opening >=35mm, and with
      reduced pain intensity. Given no difference between treatment strategies, non
      surgical treatment should be employed for TMJ closed lock before considering
      surgery. 

PMID- 24042070
TI  - Is steatosis a risk factor for hepatic blunt force injury?
AB  - Hepatic steatosis is commonly seen in association with chronic ethanol use,
      obesity, diabetes mellitus, and infections or intoxications with certain viruses
      and/or medication/chemicals. Some forensic textbooks argue that livers with fatty
      infiltration are more susceptible to trauma. A study was designed to evaluate
      whether individuals with hepatic steatosis were at greater risk for liver trauma
      than those without steatosis. Individuals dying from blunt force injuries were
      evaluated for the presence or absence of hepatic trauma and hepatic steatosis. A
      grading system of steatosis was used resulting in scores ranging from 0 to 3:
      corresponding to none, mild, moderate, and severe steatosis. A total of 171 cases
      were reviewed, including 134 men and 37 women ranging from 17 to 61 years of age
      (average 30 years). Liver injury was present in 90 cases (53%) and absent in 81
      cases (47%). A total of 78 cases (45.6%) showed no evidence of steatosis and 93
      (54.4%) showed some element of steatosis with 58 (33.9%) showing mild, 19 (11.1%)
      moderate, and 16 (9.4%) severe steatosis. Statistical analysis failed to reveal
      an increased incidence of hepatic trauma within any of the steatotic groups as
      compared with the nonsteatotic group. Therefore, it can be concluded that hepatic
      steatosis does not lead to an increased risk of sustaining blunt force liver
      trauma. 

PMID- 24042071
TI  - Xanthone derivatives from the fermentation products of an endophytic fungus
      Phomopsis sp.
AB  - Three new xanthones, 1,5-dihydroxy-3-hydroxyethyl-6-methoxycarbonylxanthone (1),
      1-hydroxy-5- methoxy-3-hydroxyethyl-6-methoxycarbonylxanthone (2), and 1-hydroxy
      3-hydroxyethyl- 8-ethoxycarbonylxanthone (3), along with seven known xanthones (4
      10) were isolated from the fermentation products of an endophytic fungus
      Phomopsis sp.. Their structures were elucidated by spectroscopic methods
      including extensive 1D- and 2D-NMR techniques. Compounds 1-10 were also tested
      for their cytotoxicity against five human tumor cell lines (NB4, A549, SHSY5Y,
      PC3, and MCF7) by MTT method using paclitaxel as positive control. Compounds 1
      and 3 showed cytotoxicity against A549 cell lines with IC50 values of 3.6 and 2.5
      MUM, respectively. In addition, 1 was cytotoxic to MCF7 cells with IC50 value of
      2.7 MUM.

PMID- 24042072
TI  - Four new diterpenoids from the roots of Euphorbia fischeriana.
AB  - Four new diterpenoids (1,4,5,9), together with 7 known diterpenoids (2,3,6
      8,10,11), were isolated from the roots to Euphorbia fischeriana. On the basis of
      1D and 2D NMR, HR-ESI-MS spectroscopic analysis, structures of the new compounds
      were elucidated as 11beta-hydroxy-8,14-epoxy-ent-abieta-13(15)-en-16,12-olide
      (1), 3,20-dihydroxy-ent-1(10), 15-rosadiene (4), 3,7-dihydroxy-ent-1(10), 15
      rosadiene (5), ingenol 6,7-epoxy-3- tetradecanoate (9). The compounds isolated
      were evaluated for their cytotoxicity against four cancer cell lines (A549,
      BEL7402, HCT116, and MDA-MB-231). Three ingenol diterpenoids (9-11) showed
      significant cytotoxicity against A549 with IC50 value of 3.35, 2.85, 2.88 MUg/mL,
      respectively.

PMID- 24042073
TI  - New triterpenoid estersaponins from the root barks of Pittosporum verticillatum
      subsp. verticillatum and evaluation of cytotoxicities.
AB  - The phytochemical investigation of the root barks of Pittosporum verticillatum
      Bojer subsp. verticillatum led to the isolation of three new triterpene saponins,
      3-O-[beta-D-glucopyranosyl-(1->2)]-[alpha-L-arabinopyranosyl-(1->3)]-[alpha-L
      arabinofuranosyl-(1->4)]-beta-D-glucuronopyranosyl-21-O-(2-acetoxy-2
      methylbutanoyl)-R1-barrigenol (1), 3-O-[beta-D-glucopyranosyl-(1->2)]-[alpha-L
      arabinopyranosyl-(1->3)]-[alpha-L-arabinofuranosyl-(1->4)]-beta-D
      glucuronopyranosyl-21-O-(2-acetoxy-2-methylbutanoyl)-28-O-acetyl-R1-barrigenol
      (2), 3-O-[beta-D-glucopyranosyl-(1->2)]-[alpha-L-arabinopyranosyl-(1->3)]-[alpha
      L-arabinofuranosyl-(1->4)]-beta-D-glucuronopyranosyl-21-O-beta,beta
      dimethylacryloyl-22-O-angeloyl-R1-barrigenol (3), and one known saponin
      senaciapittoside B (4). Their structures were elucidated mainly by 1D- and 2D-NMR
      spectroscopy and HRESIMS. Compounds 1-4 were evaluated for their cytotoxicity
      against one human cancer cell line (SW480) and one rat cardiomyoblast cell line
      (H9c2).

PMID- 24042074
TI  - [Current evidence on the motivational interview in the approach to health care
      problems in primary care].
AB  - The motivational interview has been widely used as a clinical method to promote
      behavioural changes in patients, helping them to resolve their ambivalence to
      obtain their own motivations. In the present article, a review is made of the
      main meta-analyses and systematic and narrative reviews on the efficacy of the
      motivational interview in the primary health care environment. 

PMID- 24042075
TI  - [The management of atrial fibrillation and characteristics of its current care in
      outpatients. AFABE observational study].
AB  - AIM: To provide insights into the characteristics and management of outpatients
      when their atrial fibrillation (AF) was first detected: diagnosis, treatment and
      follow-up in the context of the public health system. DESIGN: AFABE is an
      observational, multicentre descriptive study with retrospective data collection
      relating to the practice patterns, management and initial strategies of treatment
      of patients with diagnosed AF in the context of primary care, emergency and
      cardiologists of the public health system. SETTING: Primary and Specialist care.
      Baix Ebre region. Tarragona. Spain. SUBJECTS: A representative sample of 182
      subjects > 60-year-old with AF who have been randomized, recruited among the
      registered patients with AF in 22 primary care centres in the area of the study.
      MESUREMENTS: Demographic data, comorbidities (AF), CHA2DS2-VASc and HAS_BLED
      scores, and practice patterns results between Primary Care and referral services.
      RESULTS: A total of 182 patients were included (mean age 78.5 SD:7.3 years; 50%
      women). Most patients (68.3% 95%CI; 60.3-76.3) had the first contact in Primary
      Care, of which 56.3% (95%CI; 45.2-66.0) were sent to Hospital Emergency
      Department where 72.7% (95%CI: 63.5-79.0) of the oral anticoagulation and 58.4%
      (95%CI: 49.4-66.9) of antiarrhytmic treatments were started. More than half
      (55.9%:95%CI; 47.2-64.7, of patients with permanent AF were followed-up by the
      Cardiology department. CONCLUSIONS: Most patients with newly diagnosed AF made a
      first contact with Primary Care, but around half were sent to Hospital Emergency
      departments, where they were treated with an antiarrhythmic and/or oral
      anticoagulation.

PMID- 24042076
TI  - Dietary adequacy of children with autism compared with controls and the impact of
      restricted diet.
AB  - OBJECTIVE: Children with autism (AUT) may consume a restricted diet relative to
      typical peers, whether due to therapeutic measures or sensory sensitivities. The
      objective of this study was to compare children with AUT with both typically
      developing (TYP) and developmentally delayed children on nutrient and food group
      intake and overall diet quality and to evaluate the impact of diet restriction.
      METHODS: Three-day food records and interview information were analyzed from 69
      children with AUT, 14 children with developmental delay, and 37 TYP children,
      drawn from a larger longitudinal study. RESULTS: Children with AUT did not differ
      significantly from children with other developmental delays on any dietary
      measures. Although there were differences in the average intake of some nutrients
      between AUT and typical controls, only calcium and dairy were also less likely to
      be consumed in adequate amounts by the AUT group. Intentional diet restriction
      accounted for most of the differences between AUT and typical controls. On
      average, all groups had inadequate fiber, vitamin D, and vegetable intake.
      Inadequate intake of folate, grains, and dairy was noted for the AUT subgroup
      with intentional diet restrictions. Children in the AUT group not following a
      restricted diet received significantly worse Healthy Eating Index-2005 scores
      than those following a restricted diet and typical controls. These differences
      were not nutritionally significant. CONCLUSIONS: When evaluating nutritional
      adequacy of children with AUT, special consideration should be given to calcium,
      folate, dairy, and grains. Diets of all children with AUT should be evaluated for
      idiosyncratic deficiencies because of unique dietary patterns.

PMID- 24042078
TI  - The relationship between ADHD symptom dimensions, clinical correlates, and
      functional impairments.
AB  - OBJECTIVE: To better understand how heterogeneity in attention-deficit
      hyperactivity disorder (ADHD) symptoms relates to heterogeneity in functional
      impairment domains in children with ADHD after accounting for demographic
      variables and comorbidities, in particular oppositionality and internalizing
      symptoms. METHODS: Parents and teachers (n = 5663) rated child/adolescent
      impairments across impairment domains in the International Classification of
      Functioning, Disability and Health as well as symptoms of ADHD and comorbidities.
      Hierarchical regressions were conducted to assess the relationship between parent
      and teacher ratings of ADHD symptom domains and functional impairments after
      accounting for personal factors and comorbid disorders. RESULTS: Symptoms of
      inattention were the strongest predictors of ratings of academic (math, writing,
      and so on) functioning, while hyperactivity/impulsivity symptoms were the
      strongest predictor of classroom disruption even after accounting for the
      presence of learning disorders and oppositional symptoms. Symptoms of ADHD
      accounted for minimal variance in interpersonal functioning or participation in
      organized activities after controlling oppositional symptoms. CONCLUSION: The
      ADHD symptom domains demonstrate domain-specific relations with various ADHD
      related functional impairments. In addition, the results highlight the role of
      oppositionality in interpersonal relationship difficulties and participation in
      organized activities.

PMID- 24042079
TI  - Hearing difficulties in children with special health care needs.
AB  - OBJECTIVE: To determine characteristics of children with special health care
      needs (CSHCN) with hearing difficulties including patterns of hearing aid use,
      comorbidity, and social and communication function. METHODS: Bivariate and
      multivariable analysis of cross-sectional data on 40,723 children aged from birth
      to 17 years from the 2005-2006 National Survey of Children with Special Health
      Care Needs, including 1,982 (5%) with parent-reported hearing difficulties.
      RESULTS: Among CSHCN, 383 (1%) used hearing aids, representing 20% of those with
      reported hearing difficulties. Odds of hearing aid use increased with age,
      primary language other than English, and lower income. More than half (58%) of
      the aided children reported hearing difficulties even with their aid. Among CSHCN
      with cerebral palsy, 13% had reported hearing difficulties and 3% used hearing
      aids. Equivalent figures for children with Down syndrome were 24% and 4%, mental
      retardation/developmental delay 12% and 5%, and autism spectrum disorder 9% and
      2%. Overall, two-thirds of CSHCN with hearing difficulties had one or more
      sensory/developmental comorbidities; CSHCN with both hearing difficulties and a
      sensory/developmental comorbidity had highest odds of learning difficulties,
      speaking/communication difficulties, feeling anxious/depressed, acting
      out/bullying, and difficulty making friends. CSHCN with hearing difficulties
      alone, or sensory/developmental conditions alone had intermediate odds, after
      socio-demographic adjustment. CONCLUSIONS: Sensory/developmental comorbidities
      are common among CSHCN with hearing difficulties, and they are associated with
      higher odds of poorer social, communication, and educational function. Services
      for CSHCN must be equipped to address a range of hearing difficulties as well as
      sensory/developmental comorbidities and to improve social/emotional functioning
      as well as learning and communication.

PMID- 24042080
TI  - DSM-5 and autism spectrum disorders: implications for families and clinicians.
AB  - Changes in the criteria for autism spectrum disorders in the new Diagnostic and
      Statistical Manual, fifth edition (DSM-5), have raised concerns among both
      professionals and the public. This commentary reviews these changes and their
      implications for families and clinicians.

PMID- 24042081
TI  - Behavioral sleep interventions in the first six months of life do not improve
      outcomes for mothers or infants: a systematic review.
AB  - OBJECTIVE: The United Kingdom's National Institute for Health Research has
      recently invited proposals for the design of a multicomponent primary care
      package of behavioral interventions to reduce parental distress caused by
      excessive infant crying in the first 6 months of life. A systematic review was
      performed to determine whether behavioral interventions for sleep, when applied
      by parents to infants younger than 6 months, improve maternal and infant
      outcomes. METHODS: Searches of PubMed, CINAHL, and Cochrane Database of
      Systematic Reviews were conducted to identify systematic reviews, meta-analyses,
      clinical trials, and cohort studies investigating the effects of behavioral sleep
      interventions in infants younger than 6 months (January 1993-March 2013). The
      evidence is critically analyzed, according to PRISMA guidelines. RESULTS: Cry
      fuss, feeding, and sleep problems emerge out of multiple dynamically interacting
      and co-evolving variables in early life and are for this reason generically
      referred to as regulatory problems. Studies that link behavioral interventions
      for sleep in the first 6 months with positive effects on maternal and infant
      health demonstrate 3 methodological constraints. They fail to identify and
      control for feeding difficulties, fail to distinguish between the
      neurodevelopmentally different first and second halves of the first year of life,
      and apply reductive analyses to evaluations of complex interventions. Despite
      substantial investment in recent years in implementation and evaluation of
      behavioral interventions for infant sleep in the first 6 months, these strategies
      have not been shown to decrease infant crying, prevent sleep and behavioral
      problems in later childhood, or protect against postnatal depression. In
      addition, behavioral interventions for infant sleep, applied as a population
      strategy of prevention from the first weeks and months, risk unintended outcomes,
      including increased amounts of problem crying, premature cessation of
      breastfeeding, worsened maternal anxiety, and, if the infant is required to sleep
      either day or night in a room separate from the caregiver, an increased risk of
      SIDS. CONCLUSION: The belief that behavioral intervention for sleep in the first
      6 months of life improves outcomes for mothers and babies is historically
      constructed, overlooks feeding problems, and biases interpretation of data.

PMID- 24042083
TI  - Interdisciplinary collaborative future for developmental-behavioral pediatrics:
      barriers and opportunities.

PMID- 24042084
TI  - Asperger syndrome and DSM-5: a dilemma for a college freshman.
AB  - CASE: Angela is an 18-year-old college freshman who made an appointment with her
      pediatrician because of academic and social difficulties at college. She was
      diagnosed with Asperger disorder at age 6 based on difficulties relating to
      adults and peers, perseverative patterns of interest, and normal language
      development.She received special education services in middle school to help
      follow directions and complete assignments. She reports feeling very isolated
      during this time. In freshman year of high school, she insisted on discontinuing
      special education and managed with weekly private individual psychotherapy.In
      sophomore year, Angela learned strategies to get additional help from her
      teachers about assignments, and her grades improved. Socially, she formed a close
      friendship with a classmate who was also on the autistic spectrum, and she found
      a group of friends through this individual. As a senior with an upward grade
      trajectory and good SAT scores, she was admitted to a competitive 4-year college.
      In a precollege consult 6 months ago, she was anxious about fitting in.Angela
      began college classes without accommodations, but she now describes a challenging
      semester. She has not made many friends. She finds her courses difficult and does
      not fully understand assignments. She believes her peers dislike her. She thinks
      she would benefit from receiving note-taking and other services and asks you to
      document her disability for the college so that she might obtain
      accommodations.You point out that the DSM-5 eliminates the Asperger category.
      Angela is concerned. She does not believe that her profile is consistent with
      autism spectrum disorder, and she fears that being labeled as autistic will be
      prejudicial at school. Yet she is worried about retaining eligibility for
      services on the basis of a disability. How do you counsel her?

PMID- 24042082
TI  - Outcome measures for clinical trials in fragile X syndrome.
AB  - OBJECTIVE: Progress in basic neuroscience has led to identification of molecular
      targets for treatment in fragile X syndrome (FXS) and other neurodevelopmental
      disorders; however, there is a gap in translation to targeted therapies in
      humans. One major obstacle to the demonstration of efficacy in human trials has
      been the lack of generally accepted endpoints to assess improvement in function
      in individuals with FXS. To address this problem, the National Institutes of
      Health convened a meeting of leading scientists and clinicians with the goal of
      identifying and standardizing outcome measures for use as potential endpoints in
      clinical trials in FXS. METHODS: Participants in the meeting included FXS
      experts, experts in the design and implementation of clinical trials and measure
      development, and representatives from advocacy groups, industry, and federal
      agencies. RESULTS: The group generated recommendations for optimal outcome
      measures in cognitive, behavioral, and biomarker/medical domains, including
      additional testing and validation of existing measures and development of new
      measures in areas of need. Although no one endpoint or set of endpoints could be
      identified that met all criteria as an optimal measure, recommendations are
      presented in this report. CONCLUSION: The report is expected to guide the
      selection of measures in clinical trials and lead to the use of a more consistent
      battery of measures across trials. Furthermore, this will help to direct research
      toward gaps in the development of validated FXS-specific outcome measures and to
      assist with interpretation of clinical trial data by creating templates for
      measurement of treatment efficacy.

PMID- 24042086
TI  - Leptin-induced endothelial dysfunction is mediated by sympathetic nervous system
      activity.
AB  - BACKGROUND: The adipocyte-derived hormone leptin is elevated in obesity and may
      contribute to vascular risk associated with obesity. The mechanism(s) by which
      leptin affects vascular disease is unclear, although leptin has been shown to
      increase sympathetic activity. The aim of this study was to investigate the
      effect of leptin treatment on endothelial function and the role of the local
      sympathetic nervous system in mediating these effects. METHODS AND RESULTS:
      Recombinant leptin was administered to C57BL6/J mice every other day for 1 week.
      Mesenteric arteriole myography revealed that leptin treatment caused significant
      impairment of endothelium-dependent vasorelaxation. Although leptin alone did not
      raise aortic blood pressure, leptin treatment augmented the blood pressure
      response to angiotensin II. The effects of leptin on mesenteric arteriolar
      function and aortic blood pressure response to angiotensin II were neutralized
      following sympathetic denervation to the mesenteric vasculature. The superoxide
      scavenger TEMPOL was also effective in preventing the effects of leptin on
      endothelial dysfunction. CONCLUSIONS: Leptin causes endothelial dysfunction and
      enhances the effects of angiotensin II on blood pressure. These effects of leptin
      are mediated by sympathetic nervous system activation and superoxide and may
      contribute to vascular stiffness and hypertension in obesity.

PMID- 24042087
TI  - Targeting nuclear import shuttles, importins/karyopherins alpha by a peptide
      mimicking the NFkappaB1/p50 nuclear localization sequence.
AB  - BACKGROUND: We recently reported that a bifunctional nuclear transport modifier
      (NTM), cSN50.1 peptide, reduced atherosclerosis, plasma cholesterol,
      triglycerides, and glucose along with liver fat and inflammatory markers, in a
      murine model of familial hypercholesterolemia. We determined that cSN50.1
      improved lipid homeostasis by modulating nuclear transport of sterol regulatory
      element-binding proteins through interaction with importin beta. Previous studies
      established that cSN50.1 and related NTMs also modulate nuclear transport of
      proinflammatory transcription factors mediated by binding of their nuclear
      localization sequences (NLSs) to importins/karyopherins alpha. However,
      selectivity and specificity of NTMs for importins/karyopherins alpha were
      undetermined. METHODS AND RESULTS: We analyzed interaction of the NTM hydrophilic
      module, N50 peptide, derived from the NLS of NFkappaB1/p50, with endogenous human
      importins/karyopherins alpha to determine the mechanism of NTM modulation of
      importin alpha-mediated nuclear transport. We show that N50 peptide forms stable
      complexes with multiple importins/karyopherins alpha. However, only interaction
      with importin alpha5 (Imp alpha5) displayed specific, high-affinity binding. The
      2:1 stoichiometry of the N50-Imp alpha5 interaction (KD1 = 73 nmol/L, KD2 = 140
      nmol/L) indicated occupancy of both major and minor NLS binding pockets.
      Utilizing in silico 3-dimensional (3-D) docking models and comparative structural
      analysis, we identified a structural component of the Imp alpha5 major NLS
      binding pocket that may stabilize N50 binding. Imp alpha5 also displayed rapid
      stimulus-induced turnover, which could influence its availability for nuclear
      transport during the inflammatory response. CONCLUSIONS: These results provide
      direct evidence that N50 peptide selectively targets Imp alpha5, encouraging
      further refinement of NLS-derived peptides as new tools to modulate inflammatory
      disorders.

PMID- 24042088
TI  - Graphene-based in-plane micro-supercapacitors with high power and energy
      densities.
AB  - Micro-supercapacitors are important on-chip micro-power sources for miniaturized
      electronic devices. Although the performance of micro-supercapacitors has been
      significantly advanced by fabricating nanostructured materials, developing thin
      film manufacture technologies and device architectures, their power or energy
      densities remain far from those of electrolytic capacitors or lithium thin-film
      batteries. Here we demonstrate graphene-based in-plane interdigital micro
      supercapacitors on arbitrary substrates. The resulting micro-supercapacitors
      deliver an area capacitance of 80.7 MUF cm-2 and a stack capacitance of 17.9 F cm
      3. Further, they show a power density of 495 W cm-3 that is higher than
      electrolytic capacitors, and an energy density of 2.5 mWh cm-3 that is comparable
      to lithium thin-film batteries, in association with superior cycling stability.
      Such microdevices allow for operations at ultrahigh rate up to 1,000 V s-1, three
      orders of magnitude higher than that of conventional supercapacitors. Micro
      supercapacitors with an in-plane geometry have great promise for numerous
      miniaturized or flexible electronic applications.

PMID- 24042089
TI  - An exploratory study of staff nurses' knowledge of delirium in the medical ICU:
      an Asian perspective.
AB  - AIM: The aim of this study was to establish intensive care unit nurses' knowledge
      of delirium within an acute tertiary hospital within South East Asia. BACKGROUND:
      Delirium is a common, life threatening and often preventable cause of morbidity
      and mortality among older patients. Undetected and untreated delirium is a
      catalyst to increased mortality, morbidity, functional decline and results in
      increased requirement for nursing care, healthcare expense and hospital length of
      stay. However, despite effective assessment tools to identify delirium in the
      acute setting, there still remains an inability of ICU nurses' to accurately
      identify delirium in the critically ill patient especially that of hypoactive
      delirium. METHOD: A purposive sample of 53 staff nurses from a 13-bedded medical
      intensive care unit within an acute tertiary teaching hospital in South East Asia
      were asked to participate. A 40 item 5-point Likert scale questionnaire was
      employed to determine the participants' knowledge of the signs and symptoms; the
      risk factors and negative outcomes of delirium. RESULTS: The overall positively
      answered mean score was 27 (67.3%) out of a possible 40 questions. Mean scores
      for knowledge of signs and symptoms, risk factors and negative outcomes were 9.52
      (63.5%, n=15), 11.43 (63.5%, n=17) and 6.0 (75%, n=8), respectively. CONCLUSION:
      Whilst the results of this study are similar to others taken from a western
      perspective, it appeared that the ICU nurses in this study demonstrated limited
      knowledge of the signs and symptoms, risk factors and negative outcomes of
      delirium in the critically patient. The implications for practice of this are
      important given the outcomes of untreated delirium.

PMID- 24042091
TI  - The effect of hip arthroplasty on the speed of walking.
AB  - Osteoarthritis of the hip presents itself with gait disturbances, such as
      decreased speed of walking and limp, regardless of the presence of pain. In most
      cases, patients decide to undergo surgical procedure as a result of pain and
      walking difficulties. The purpose of this study was to analyze gait speed in a
      group of 86 patients who have undergone hip arthroplasty. The methodology has
      consisted of analysis of walking speed over a distance of 20 meters performed
      prior to and following surgical treatment. The results indicated that, in most
      cases, surgical treatment was associated with significant improvement in the
      speed of walking.   

PMID- 24042090
TI  - Spatial and social factors drive anemia in Congolese women.
AB  - Anemia is common in women of child-bearing age in the Democratic Republic of the
      Congo (DRC). As part of the 2007 DRC Demographic and Health Survey (DHS), 4638
      women of childbearing age (including 526 pregnant women) were tested for HIV and
      had the hemoglobin content of their blood recorded. We used the leftover dried
      blood spots to assess malaria prevalence using PCR assays. The DHS provided
      extensive information on individuals, as well as the geographic coordinates of
      household clusters which enabled us to derive several variables that characterize
      the spatial context of these clusters. Multilevel analyses were conducted to
      determine individual and contextual risk factors for anemia. Prevalence varied
      geographically; the odds of anemia were associated with both one's ethnic group
      and the amount and type of nearby agriculture. The odds were not affected by HIV
      or malaria status. 

PMID- 24042092
TI  - Methamphetamine alters reference gene expression in nigra and striatum of adult
      rat brain.
AB  - The nigrostriatal dopaminergic system is a major lesion target for
      methamphetamine (MA), one of the most addictive and neurotoxic drugs of abuse.
      High doses of MA alter the expression of a large number of genes. Reference genes
      (RGs) are considered relatively stable and are often used as standards for
      quantitative real-time PCR (qRT-PCR) reactions. The purpose of this study was to
      determine whether MA altered the expression of RGs and to identify the
      appropriate RGs for gene expression studies in animals receiving MA. Adult male
      Sprague-Dawley rats were treated with high doses of MA or saline. Striatum and
      substantia nigra were harvested at 2h or 24h after MA administration. The
      expression and stability of 10 commonly used RGs were examined using qRT-PCR and
      then evaluated by geNorm and Normfinder. We found that MA altered the expression
      of selected RGs. These candidate RGs presented differential stability in the
      striatum and in substantia nigra at both 2h and 24h after MA injection. Selection
      of an unstable RG as a standard altered the significance of tyrosine hydroxylase
      (TH) mRNA expression after MA administration. In conclusion, our data show that
      MA site- and time-dependently altered the expression of RGs in nigrostriatal
      dopaminergic system. These temporal and spatial factors should be considered when
      selecting appropriate RGs for interpreting the expression of target genes in
      animals receiving MA. 

PMID- 24042093
TI  - Clinical and genetic features of hearing loss in facioscapulohumeral muscular
      dystrophy.
AB  - OBJECTIVE: To describe the hearing loss in facioscapulohumeral muscular dystrophy
      (FSHD) and examine the relationship to genotype. METHODS: Medical records of all
      individuals with FSHD seen at the University of Iowa neuromuscular clinic between
      July 2006 and July 2012 (n = 59) were reviewed. Eleven had significant hearing
      loss and no non-FSHD cause. All available audiology records for these individuals
      were analyzed. The relationship between the FSHD mutation (EcoRI/BlnI fragment
      size) and hearing loss was evaluated using a logistic regression analysis.
      RESULTS: In patients with hearing loss, recalled age at onset of facial weakness
      ranged from birth to 5 years and shoulder weakness was 3 to 15 years. The age at
      diagnosis of hearing loss ranged from birth to 7 years. Only 2 were identified by
      newborn hearing screen. Most audiograms demonstrated a bilateral, sloping, high
      frequency sensorineural hearing loss. Of the 4 patients with more than 5 years of
      data, 3 had progression of hearing loss. Logistic regression showed statistically
      significant negative association between the presence of hearing loss and
      EcoRI/BlnI fragment size (p = 0.0207). CONCLUSIONS: FSHD with a small EcoRI/BlnI
      fragment is associated with a bilateral, progressive, sloping, high-frequency
      hearing loss with onset in childhood. Patients with FSHD and small EcoRI/BlnI
      fragment sizes should have hearing screened, even if the child passed newborn
      hearing screening.

PMID- 24042094
TI  - Predicting hearing loss in facioscapulohumeral muscular dystrophy.

PMID- 24042095
TI  - Prevalence of white matter lesions and stroke in children with migraine.
AB  - OBJECTIVES: To determine the prevalence of white matter lesions (WMLs) and
      infarcts in children with migraine and whether pediatric migraine could be a risk
      factor for silent ischemic lesions or stroke. METHODS: Prospectively collected
      data from 1,008 pediatric patients with headache were reviewed. The MRI data were
      collected and retrospectively reviewed. RESULTS: Of the 926 patients diagnosed
      with migraine, 375 patients had MRIs and 115 had abnormalities, of which 39 had
      WMLs. Among them, 24 (6% of migraine) patients had incidental white matter
      findings without known neurovascular disease, risk factors, or etiologies for
      WMLs. The prevalence of WMLs is more common in migraine with aura (10%) than
      without aura (4%) (p = 0.038), but it is not statistically significant compared
      with controls (4%) (p = 0.119). Deep WMLs are more prevalent than periventricular
      lesions; these are detected mainly in the frontal and parietal lobes. No lesions
      appeared to be infarct-like lesions. There was no association between the total
      lesion load and chronicity or the frequency of migraine. WMLs are nonprogressive.
      Pediatric migraineurs with aura do not develop stroke, based on the available
      follow-up data. CONCLUSION: WMLs in pediatric patients with migraine and aura are
      no more prevalent than in controls. They appear to be benign and are not
      associated with stroke.

PMID- 24042096
TI  - Mice with human livers.
AB  - Animal models are used to study many aspects of human disease and to test
      therapeutic interventions. However, some very important features of human biology
      cannot be replicated in animals, even in nonhuman primates or transgenic rodents
      engineered with human genes. Most human microbial pathogens do not infect animals
      and the metabolism of many xenobiotics is different between human beings and
      animals. The advent of transgenic immune-deficient mice has made it possible to
      generate chimeric animals harboring human tissues and cells, including
      hepatocytes. The liver plays a central role in many human-specific biological
      processes and mice with humanized livers can be used to model human metabolism,
      liver injury, gene regulation, drug toxicity, and hepatotropic infections. 

PMID- 24042097
TI  - In situ recognition of cell-surface glycans and targeted imaging of cancer cells.
AB  - Fluorescent sensors capable of recognizing cancer-associated glycans, such as
      sialyl Lewis X (sLe(x)) tetrasaccharide, have great potential for cancer
      diagnosis and therapy. Studies on water-soluble and biocompatible sensors for in
      situ recognition of cancer-associated glycans in live cells and targeted imaging
      of cancer cells are very limited at present. Here we report boronic acid
      functionalized peptide-based fluorescent sensors (BPFSs) for in situ recognition
      and differentiation of cancer-associated glycans, as well as targeted imaging of
      cancer cells. By screening BPFSs with different structures, it was demonstrated
      that BPFS1 with a FRGDF peptide could recognize cell-surface glycan of sLe(x)
      with high specificity and thereafter fluorescently label and discriminate cancer
      cells through the cooperation with the specific recognition between RGD and
      integrins. The newly developed peptide-based sensor will find great potential as
      a fluorescent probe for cancer diagnosis.

PMID- 24042098
TI  - Metatarsophalangeal joint function during sprinting: a comparison of barefoot and
      sprint spike shod foot conditions.
AB  - The metatarsophalangeal joint is an important contributor to lower limb
      energetics during sprint running. This study compared the kinematics, kinetics
      and energetics of the metatarsophalangeal joint during sprinting barefoot and
      wearing standardized sprint spikes. The aim of this investigation was to
      determine whether standard sprinting footwear alters the natural motion and
      function of the metatarsophalangeal joint exhibited during barefoot sprint
      running. Eight trained sprinters performed maximal sprints along a runway, four
      sprints in each condition. Three-dimensional high-speed (1000 Hz) kinematic and
      kinetic data were collected at the 20 m point. Joint angle, angular velocity,
      moment, power and energy were calculated for the metatarsophalangeal joint.
      Sprint spikes significantly increase sprinting velocity (0.3 m/s average
      increase), yet limit the range of motion about the metatarsophalangeal joint
      (17.9% average reduction) and reduce peak dorsiflexion velocity (25.5% average
      reduction), thus exhibiting a controlling affect over the natural behavior of the
      foot. However, sprint spikes improve metatarsophalangeal joint kinetics by
      significantly increasing the peak metatarsophalangeal joint moment (15% average
      increase) and total energy generated during the important push-off phase (0.5 J
      to 1.4 J). The results demonstrate substantial changes in metatarsophalangeal
      function and potential improvements in performance-related parameters due to
      footwear. 

PMID- 24042099
TI  - Prevalence of Helicobacter pylori cagA and vacA genes in Cypriot patients.
AB  - INTRODUCTION: The prevalence of H. pylori varies with geographic locations. To
      date there are no epidemiological data on its prevalence in Cyprus; therefore, we
      determined the prevalence and molecular characteristics of H. pylori infection in
      Cypriot patients. METHODOLOGY: DNA extracted from 103 gastric biopsies was
      analyzed for the presence of H. pylori by PCR using primers for ureA. H. pylori
      positive biopsies were characterized by PCR using specific primers for cagA and
      vacA genes. The presence of clarithromycin-associated resistant mutations such as
      A2143G, A2142G, A2142C in 23S rRNA gene of H. pylori-positive patients was
      determined using a real-time PCR allelic discrimination assay. RESULTS: H. pylori
      was detected in 41 (39.8%) biopsies and, out of these, 17 (41.5%) tested positive
      for the cagA gene. The vacA alleles m1, m2, s1a, s1b, and s2 were detected in 7
      (17.1%), 34 (82.9%), 12 (29.3%), 2 (4.9%), and 22 (53.7%) isolates, respectively.
      One (2.4%) biopsy was vacA s1a and s2-positive while one (2.4%) was positive for
      vacA s1a, s1b, and s2. Three (7.3%) biopsies were untypable for vacA s1, s1b, and
      s2. The majority (35; 85.4%) of strains were susceptible to clarithromycin while
      two (4.9%) had the A2143G mutation. Three (7.3%) had a mixture of an A2143G point
      mutant and susceptible strains while one (2.4%) had a mixture of an A2142G point
      mutant and susceptible strains. CONCLUSIONS: The distribution of the virulence
      factors cagA and vacA in the Cypriot strains resembled that of strains
      circulating in Middle Eastern countries geographically close to Cyprus.

PMID- 24042100
TI  - A study on the effect of Helicobacter pylori infection on p53 expression in
      gastric cancer and gastritis tissues.
AB  - INTRODUCTION: Helicobacter pylori cause damage to gastric epithelial cells and
      alterations in the p53 gene that lead to cancer development. This study aimed to
      determine the correlation of p53 expression with H. pylori using
      immunohistochemistry, RFLP-PCR, and histopathology. METHODOLOGY: Gastric biopsy
      samples from gastric cancer (GC) (n = 54) and gastritis (n = 31) patients were
      examined for histopathological changes and expression of p53 protein by
      immunohistochemistry. RESULTS: Immunohistochemical analysis of p53 protein
      expression in H. pylori-positive GC sections showed an average of 44.3% positive
      cells in tumors and 6.9% in normal tissues, as compared to 16.4% and 4.4% in H.
      pylori-negative sections. P53 expression showed significant association with H.
      pylori (P = 0.005), invasion depth (P = 0.029) and inflammation reaction (P =
      0.008). In gastritis sections, no difference in the average p53 staining in H.
      pylori-positive or -negative sections was seen. PCR-RFLP results also showed no
      difference in genotype frequencies of p53 in H. pylori-positive or -negative
      gastritis sections. Histopathology study of H. pylori-positive GC sections showed
      that 97.2% were the intestinal type and 2.8% the diffuse type, while in H. pylori
      negative sections 35.2% were the intestinal type and 64.8% the diffuse type.
      Biopsy sections from H. pylori-positive gastritis patients revealed more severe
      inflammation than those of H. pylori-negative patients. CONCLUSION: Our results
      show that H. pylori infection affects p53 expression in GC. The average p53
      expression was significantly higher in tumor than in normal tissues. In gastritis
      sections p53 expression was significantly associated with H. pylori.

PMID- 24042101
TI  - University students' knowledge and attitudes towards leprosy.
AB  - INTRODUCTION: Patients with leprosy may be affected psychologically and socially
      by the negative attitude of society toward leprosy, caused by widespread
      ignorance and prevailing stereotypes surrounding the disease. This study aimed to
      determine the knowledge and attitudes toward leprosy among students at the
      University of Guadalajara. METHODOLOGY: This descriptive cross-sectional study
      included 1,300 students over 18 years of age from various Thematic University
      Centres in Guadalajara. Students' degree subjects included the health sciences,
      humanities, exact sciences (i.e., chemistry, physics), arts, biological
      agricultural sciences, and administration. Students were randomly selected
      regardless of gender and all students were enrolled in either the first, second,
      or third year of their undergraduate studies. RESULTS: Overall, students showed
      an intermediate level of knowledge of leprosy. Results showed that 67% correctly
      responded that leprosy is an infectious disease, 64% knew of the presence of skin
      lesions, and 60% knew that a microbe causes the disease. Furthermore, 45%
      correctly responded that leprosy is a disease associated with poverty and 40%
      responded that leprosy is disabling. Only 31% stated that leprosy is curable.
      Negative attitudes were evident regarding the question of employing a leprosy
      patient (57%) and having a leprosy patient as a spouse or partner (30%).
      DISCUSSION: The results revealed that there is insufficient knowledge of and poor
      attitudes toward leprosy among students at the University of Guadalajara. It is
      necessary to improve current health education measures by using updated
      educational strategies to reduce the stigma of leprosy and the segregation of
      leprosy patients and their families.

PMID- 24042102
TI  - HBsAg, anti-HCV, anti-HIV 1/2 and syphilis seroprevalence in healthy volunteer
      blood donors in southeastern Anatolia.
AB  - INTRODUCTION: This study investigated the seroprevalence of hepatitis B virus
      surface antigen (HBsAg), antibody against hepatitis C virus (anti-HCV), antibody
      against human immunodeficiency virus type 1/2 (anti-HIV 1/2), and antibody
      against Treponema pallidum (anti-Treponemal or syphilis antibody) in healthy
      volunteer blood donors, and assessed their distribution according to the years
      and genders. METHODOLOGY: HBsAg, anti-HCV, anti-HIV 1/2, and syphilis screening
      results of a total of 266,035 healthy volunteer blood donors who had been
      admitted for blood donation to the Regional Blood Center of Dicle University
      Hospital between January 2000 and December 2010 were evaluated, retrospectively.
      HBsAg, anti-HCV, and anti-HIV 1/2 screening were performed using a fully
      automated device with the microparticle enzyme immunoassay method (MEIA).
      Syphilis screening was performed by Rapid Plasma Reagin (RPR) carbon test between
      January 2000 and December 2009, and by using a fully automated device with the
      MEIA method between January 2010 and December 2010. RESULTS: Of 266,035 healthy
      volunteer blood donors, 259,384 (97.5%) were male and 6,651 (2.5%) were female.
      Statistically, there was not any significant difference between male and female
      genders for HBsAg, anti-HCV and syphilis seropositivities (P = 0.729, P = 0.748,
      and P = 0.861, respectively). HBsAg was found to be positive in 8,422 (3.17%),
      anti-HCV in 1,703 (0.64%), anti-HIV 1/2 in one (0.0004%) of 266,035 healthy
      volunteer blood donors, and syphilis antibody with RPR in 166 (0.07%) of 246,341
      healthy volunteer blood donors. CONCLUSION: Blood donor forms should be carefully
      tailored to improve the identification of possible risks of transfusion
      transmitted infections.

PMID- 24042103
TI  - Epidemiology of Candida blood stream infections: experience of a tertiary care
      centre in North India.
AB  - INTRODUCTION: Bloodstream infections due to Candida species are becoming a major
      cause of morbidity and mortality in hospitalized patients. The spectrum of
      candidemia has changed with the emergence of non-albicans Candida species,
      especially among critically ill patients. METHODOLOGY: In a retrospective study
      (July 2009 to December 2009) on candidemia, various Candida species isolated from
      blood cultures were characterized and studied along with the determination of
      their antifungal susceptibility to amphotericin B, itraconazole, and fluconazole
      by Etest. Probable risk factors for patients in the intensive care unit (ICU)
      presenting with candidemia were also analyzed. RESULTS: During the study period,
      a total of 4651 samples were received, out of which 468 samples (10.06%) were
      positive for growth of organisms: 441 (94.20%) aerobic bacterial pathogens and 27
      (5.79%) Candida species. The most common Candida spp. isolate was C. tropicalis
      (40.8%) followed by C. albicans (29.6%), C. glabrata (18.5%) and others (11.1%).
      Out of the 27 Candida strains, 24 (88.9%) were isolated from patients treated in
      the ICU. Among these, association of previous use of broad-spectrum antibiotics
      in 22 patients (91.6%) and central line catheter insertion in 20 patients (83.3%)
      were found to be statistically significant as compared to non-candidemia patients
      (p <0.05). Antifungal susceptibility testing of the isolates revealed a lower
      level of drug resistance to amphotericin B (18.5% of the isolates) versus 77.8%
      resistance to fluconazole. CONCLUSION: Rapid changes in the rate of infection,
      potential risk factors, and emergence of non-albicans Candida demand continued
      surveillance of this serious bloodstream fungal infection.

PMID- 24042104
TI  - Strengthening tuberculosis diagnosis in a low-resource setting: experience
      learned in Dodoma, Tanzania.
AB  - INTRODUCTION: Diagnosing tuberculosis in low-resource settings mostly relies on
      sputum smear microscopy. Improvement through capacity building is a priority.
      This project aimed to strengthen tuberculosis diagnosis at an intermediate level
      laboratory. METHODOLOGY: The Italian National Institute for Infectious Diseases
      and the Italian Development Cooperation closely collaborated with regional and
      national institutions and reference laboratories to provide laboratory setup,
      equipment and reagents, personnel training, and the implementation of culture and
      quality assessment programs at Dodoma Regional Hospital, Dodoma, Tanzania.
      RESULTS: Microscopy sensitivity was increased, personnel were trained, and
      culture techniques and quality assessment programs were introduced. CONCLUSIONS:
      Implementing tuberculosis diagnosis in resource-constrained settings is feasible
      and represents a basis for further strengthening.

PMID- 24042105
TI  - Cryptococcal meningitis with secondary cutaneous involvement in an
      immunocompetent host.
AB  - Cryptococcosis is a potentially fatal fungal disease caused by variants of
      Cryptococcus neoformans species.  The respiratory tract is the usual portal of
      entry, with a peculiar predilection to invade the central nervous system.  The
      skin can be secondarily involved in disseminated infection or be exceptionally
      involved as primary cutaneous infection by inoculation.  The disease is mostly
      seen in immunodeficiency states.  The diagnosis is frequently unsuspected in
      immunocompetent patients. We report a case of disseminated cryptococcal
      meningitis in an immunocompetent young adult. The cutaneous eruption prompted the
      accurate diagnosis.  The patient, a 20-year-old female, had fever, cough,
      headache and intractable vomiting for the past two months and was being managed
      as a case of tuberculous meningitis. Two weeks after starting antituberculous
      treatment she developed umbilicated papules on the head and neck region.
      Necessary laboratory workup identified C. neoformans in cerebrospinal fluid (CSF)
      and skin specimens.  The titers of cryptococcal antigen were measured in CSF and
      serum for diagnostic and prognostic purposes.  Anti-fungal treatment resulted in
      regression of the cutaneous lesions and resolution of systemic complaints. The
      case highlights the need for high degree of suspicion, especially in healthy
      young adults, in the diagnosis of cryptococcosis. The cutaneous eruptions can be
      the first manifestation or a diagnostic clue of enormous significance. 

PMID- 24042106
TI  - Risk factors for carbapenem-resistant Pseudomonas aeruginosa infection in a
      tertiary care hospital in Serbia.

PMID- 24042107
TI  - Increased Body Weight of the BAC HD Transgenic Mouse Model of Huntington's
      Disease Accounts for Some but Not All of the Observed HD-like Motor Deficits.
AB  - The genome of the Bacterial Artificial Chromosome (BAC) transgenic mouse model of
      Huntington's Disease (BAC HD) contains the 170 kb human HTT locus modified by the
      addition of exon 1 with 97 mixed CAA-CAG repeats. BAC HD mice present robust
      behavioral deficits in both the open field and the accelerating rotarod tests,
      two standard behavioral assays of motor function. BAC HD mice, however, also
      typically present significantly increased body weights relative to wildtype
      littermate controls (WT) which potentially confounds the interpretation of any
      motor deficits associated directly with the effects of mutant huntingtin. In
      order to evaluate this possible confound of body weight, we directly compared the
      performance of BAC HD and WT female mice under food restricted versus free
      feeding conditions in both the open field and rotarod tasks to test the
      hypothesis that some of the motor deficits observed in this HTT-transgenic mouse
      line results solely from increased body weight. Our results suggest that the
      rotarod deficit exhibited by BAC HD mice is modulated by both body weight and non
      body weight factors resulting from overexpression of full length mutant Htt. When
      body weights of WT and BAC HD transgenic mice were normalized using restricted
      feeding, the deficits exhibited by BAC HD mice on the rotarod task were less
      marked, but were still significant. Since the rotarod deficit between WT and BAC
      HD mice is attenuated when body weight is normalized by food restriction,
      utilization of this task in BAC HD mice during pre-clinical evaluation must be
      powered accordingly and results carefully considered as therapeutic benefit can
      result from decreased overall body weight and or motoric improvement that may not
      be related to body mass. Furthermore, after controlling for body weight
      differences, the hypoactive phenotype displayed by ad libitum fed BAC HD mice in
      the open field assay was not observed in the BAC HD mice undergoing food
      restriction. These findings suggest that assessment of spontaneous locomotor
      activity, as measured in the open field test, may not be the appropriate
      behavioral endpoint to evaluate the BAC HD mouse during preclinical evaluation
      since it appears that the apparent hypoactive phenotype in this model is driven
      primarily by body weight differences. 

PMID- 24042108
TI  - Global transcriptome analysis of Staphylococcus aureus biofilms in response to
      innate immune cells.
AB  - The potent phagocytic and microbicidal activities of neutrophils and macrophages
      are among the first lines of defense against bacterial infections. Yet
      Staphylococcus aureus is often resistant to innate immune defense mechanisms,
      especially when organized as a biofilm. To investigate how S. aureus biofilms
      respond to macrophages and neutrophils, gene expression patterns were profiled
      using Affymetrix microarrays. The addition of macrophages to S. aureus static
      biofilms led to a global suppression of the biofilm transcriptome with a wide
      variety of genes downregulated. Notably, genes involved in metabolism, cell wall
      synthesis/structure, and transcription/translation/replication were among the
      most highly downregulated, which was most dramatic at 1 h compared to 24 h
      following macrophage addition to biofilms. Unexpectedly, few genes were enhanced
      in biofilms after macrophage challenge. Unlike coculture with macrophages,
      coculture of S. aureus static biofilms with neutrophils did not greatly influence
      the biofilm transcriptome. Collectively, these experiments demonstrate that S.
      aureus biofilms differentially modify their gene expression patterns depending on
      the leukocyte subset encountered. 

PMID- 24042109
TI  - Functional comparison of Plasmodium falciparum transmission-blocking vaccine
      candidates by the standard membrane-feeding assay.
AB  - Recently, there has been a renewed interest in the development of transmission
      blocking vaccines (TBV) against Plasmodium falciparum malaria. While several
      candidate TBVs have been reported, studies directly comparing them in functional
      assays are limited. To this end, recombinant proteins of TBV candidates Pfs25,
      Pfs230, and PfHAP2 were expressed in the wheat germ cell-free expression system.
      Outbred CD-1 mice were immunized twice with the antigens. Two weeks after the
      second immunization, IgG levels were measured by enzyme-linked immunosorbent
      assay (ELISA), and IgG functionality was assessed by the standard membrane
      feeding assay (SMFA) using cultured P. falciparum NF54 gametocytes and Anopheles
      stephensi mosquitoes. All three recombinant proteins elicited similar levels of
      antigen-specific IgG judged by ELISA. When IgGs purified from pools of immune
      serum were tested at 0.75 mg/ml in the SMFA, all three IgGs showed 97 to 100%
      inhibition in oocyst intensity compared to control IgG. In two additional
      independent SMFA evaluations, anti-Pfs25, anti-Pfs230, and anti-PfHAP2 IgGs
      inhibited oocyst intensity in a dose-dependent manner. When all three data sets
      were analyzed, anti-Pfs25 antibody showed significantly higher inhibition than
      the other two antibodies (P < 0.001 for both), while there was no significant
      difference between the other two (P = 0.15). A proportion of plasma samples
      collected from adults living in an area of malaria endemicity in Mali recognized
      Pfs230 and PfHAP2. This is the first study showing that the HAP2 protein of P.
      falciparum can induce transmission-blocking antibody. The current study supports
      the possibility of using this system for a comparative study with multiple TBV
      candidates. 

PMID- 24042110
TI  - Protective humoral immunity elicited by a needle-free malaria vaccine comprised
      of a chimeric Plasmodium falciparum circumsporozoite protein and a Toll-like
      receptor 5 agonist, flagellin.
AB  - Immunization with Plasmodium sporozoites can elicit high levels of sterile
      immunity, and neutralizing antibodies from protected hosts are known to target
      the repeat region of the circumsporozoite (CS) protein on the parasite surface.
      CS-based subunit vaccines have been hampered by suboptimal immunogenicity and the
      requirement for strong adjuvants to elicit effective humoral immunity. Pathogen
      associated molecular patterns (PAMPs) that signal through Toll-like receptors
      (TLRs) can function as potent adjuvants for innate and adaptive immunity. We
      examined the immunogenicity of recombinant proteins containing a TLR5 agonist,
      flagellin, and either full-length or selected epitopes of the Plasmodium
      falciparum CS protein. Mice immunized with either of the flagellin-modified CS
      constructs, administered intranasally (i.n.) or subcutaneously (s.c.), developed
      similar levels of malaria-specific IgG1 antibody and interleukin-5 (IL-5)
      producing T cells. Importantly, immunization via the i.n. but not the s.c. route
      elicited sporozoite neutralizing antibodies capable of inhibiting >90% of
      sporozoite invasion in vitro and in vivo, as measured using a transgenic rodent
      parasite expressing P. falciparum CS repeats. These findings demonstrate that
      functional sporozoite neutralizing antibody can be elicited by i.n. immunization
      with a flagellin-modified P. falciparum CS protein and raise the potential of a
      scalable, safe, needle-free vaccine for the 40% of the world's population at risk
      of malaria. 

PMID- 24042111
TI  - Structure-function studies of the Neisseria gonorrhoeae major outer membrane
      porin.
AB  - The major outer membrane porin (PorB) expressed by Neisseria gonorrhoeae plays
      multiple roles during infection, in addition to its function as an outer membrane
      pore. We have generated a panel of mutants of N. gonorrhoeae strain FA1090
      expressing a variety of mutant porB genes that all function as porins. We
      identified multiple regions of porin that are involved in its binding to the
      complement regulatory factors C4b-binding protein and factor H and confirmed that
      the ability to bind at least one factor is required for FA1090 to survive the
      bactericidal effects of human serum. We tested the ability of these mutants to
      inhibit both apoptosis and the oxidative burst in polymorphonuclear leukocytes
      but were unable to identify the porin domains required for either function. This
      study has identified nonessential porin domains and some potentially essential
      portions of the protein and has further expanded our understanding of the
      contribution of the porin domains required for complement regulation. 

PMID- 24042112
TI  - Bacillus anthracis has two independent bottlenecks that are dependent on the
      portal of entry in an intranasal model of inhalational infection.
AB  - Bacillus anthracis can cause inhalational anthrax. Murine inhalational B.
      anthracis infections have two portals of entry, the nasal mucosa-associated
      lymphoid tissue (NALT) and the lumen of the lungs. Analysis of the dissemination
      from these sites is hindered because infections are asynchronous and asymptomatic
      until the hosts near death. To further understand and compare how B. anthracis
      disseminates from these two different environments, clonal analysis was employed
      using a library of equally virulent DNA-tagged clones of a luminescent Sterne
      strain. Luminescence was used to determine the origin of the infection and
      monitor the dissemination in vivo. The number of clones and their proportions in
      the portals of entry, lymph nodes draining the portals, and kidneys were
      analyzed. Clonal analysis indicated a bottleneck for both portals of entry, yet
      the extent and location of the reduction in represented clones differed between
      the routes. In NALT-based infections, all clones were found to germinate in the
      NALT, but they underwent a bottleneck as the infection spread to the cervical
      lymph node. However, lung-based infections underwent a bottleneck in a focal
      region of growth within the lung lumen and did not need to spread through the
      mediastinal lymph nodes to cause a systemic infection. Further, the average
      number of clones found in the kidney and the rate at which genetic drift was
      affecting the disseminated populations were significantly higher in lung-based
      infections. Collectively, the data suggested that differences in the host
      environment alter dissemination of B. anthracis depending on the site of initial
      colonization and growth. 

PMID- 24042113
TI  - Periodontal treatment downregulates protease-activated receptor 2 in human
      gingival crevicular fluid cells.
AB  - Protease-activated receptor 2 (PAR2) is implicated in the pathogenesis of chronic
      inflammatory diseases, including periodontitis; it can be activated by gingipain
      and produced by Porphyromonas gingivalis and by neutrophil protease 3 (P3). PAR2
      activation plays a relevant role in inflammatory processes by inducing the
      release of important inflammatory mediators associated with periodontal
      breakdown. The effects of periodontal treatment on PAR2 expression and its
      association with levels of proinflammatory mediators and activating proteases
      were investigated in chronic periodontitis patients. Positive staining for PAR2
      was observed in gingival crevicular fluid cells and was reflective of tissue
      destruction. Overexpression of PAR2 was positively associated with inflammatory
      clinical parameters and with the levels of interleukin-6 (IL-6), IL-8, tumor
      necrosis factor alpha, matrix metalloprotease 2 (MMP-2), MMP-8, hepatocyte growth
      factor, and vascular endothelial growth factor. Elevated levels of gingipain and
      P3 and decreased levels of dentilisin and the protease inhibitors secretory
      leukocyte protease inhibitor and elafin were also associated with PAR2
      overexpression. Healthy periodontal sites from individuals with chronic
      periodontitis showed diminished expression of PAR2 mRNA and the PAR2 protein (P <
      0.05). Furthermore, periodontal treatment resulted in decreased PAR2 expression
      and correlated with decreased expression of inflammatory mediators and activating
      proteases. We concluded that periodontal treatment resulted in decreased levels
      of proteases and that proinflammatory mediators are associated with decreased
      PAR2 expression, suggesting that PAR2 expression is influenced by the presence of
      periodontal infection and is not a constitutive characteristic favoring
      periodontal inflammation. 

PMID- 24042114
TI  - Toll-like receptor 7 mediates early innate immune responses to malaria.
AB  - Innate immune recognition of malaria parasites is the critical first step in the
      development of the host response. At present, Toll-like receptor 9 (TLR9) is
      thought to play a central role in sensing malaria infection. However, we and
      others have observed that Tlr9(-/-) mice, in contrast to mice deficient in the
      downstream adaptor, Myeloid differentiation primary response gene 88 (MYD88),
      exhibit few deficiencies in immune function during early infection with the
      malaria parasite Plasmodium chabaudi, implying that another MYD88-dependent
      receptor also contributes to the antimalarial response. Here we use candidate
      based screening to identify TLR7 as a key sensor of early P. chabaudi infection.
      We show that TLR7 mediates a rapid systemic response to infection through
      induction of cytokines such as type I interferons (IFN-I), interleukin 12, and
      gamma interferon. TLR7 is also required for induction of IFN-I by other species
      and strains of Plasmodium, including an etiological agent of human disease, P.
      falciparum, suggesting that malaria parasites harbor a common pathogen-associated
      molecular pattern (PAMP) recognized by TLR7. In contrast to the nonredundant
      requirement for TLR7 in early immune activation, sensing through both TLR7 and
      TLR9 was required for proinflammatory cytokine production and immune cell
      activation during the peak of parasitemia. Our findings indicate that TLR7 plays
      a central role in early immune activation during malaria infection, whereas TLR7
      and TLR9 contribute combinatorially to immune responses as infection progresses. 

PMID- 24042115
TI  - Comparison of cytokine immune responses to Brucella abortus and Yersinia
      enterocolitica serotype O:9 infections in BALB/c mice.
AB  - Brucella abortus and Yersinia enterocolitica serotype O:9 serologically cross
      react in the immune response with the host; therefore, our aim was to compare the
      immune responses to these two pathogens. We selected typical B. abortus and Y.
      enterocolitica O:9 strains to study the cytokine immune response and the
      histopathological changes in livers and spleens of BALB/c mice. The data showed
      the cytokine responses to the two strains of pathogens were different, where the
      average levels of granulocyte-macrophage colony-stimulating factor (GM-CSF),
      gamma interferon (IFN-gamma), interleukin-12 (IL-12), and tumor necrosis factor
      alpha (TNF-alpha) were higher with B. abortus infections than with Y.
      enterocolitica O:9 infections, especially for IFN-gamma, while the IL-10 level
      was lower and the levels of IL-1beta, IL-4, IL-5, and IL-6 were similar. The
      histopathological effects in the livers and spleens of the BALB/c mice with B.
      abortus and Y. enterocolitica O:9 infections were similar; however, the
      pathological changes in the liver were greater with B. abortus infections, while
      damage in the spleen was greater with Y. enterocolitica O:9 infections. These
      observations show that different cytokine responses and histopathological changes
      occur with B. abortus and Y. enterocolitica O:9 infections. 

PMID- 24042116
TI  - Interleukin-10 (IL-10) inhibits Borrelia burgdorferi-induced IL-17 production and
      attenuates IL-17-mediated Lyme arthritis.
AB  - Previous studies have shown that cells and cytokines associated with interleukin
      17 (IL-17)-driven inflammation are involved in the arthritic response to Borrelia
      burgdorferi infection. Here, we report that IL-17 is a contributing factor in the
      development of Lyme arthritis and show that its production and histopathological
      effects are regulated by interleukin-10 (IL-10). Spleen cells obtained from B.
      burgdorferi-infected, "arthritis-resistant" wild-type C57BL/6 mice produced low
      levels of IL-17 following stimulation with the spirochete. In contrast, spleen
      cells obtained from infected, IL-10-deficient C57BL/6 mice produced a significant
      amount of IL-17 following stimulation with B. burgdorferi. These mice developed
      significant arthritis, including erosion of the bones in the ankle joints. We
      further show that treatment with antibody to IL-17 partially inhibited the
      significant hind paw swelling and histopathological changes observed in B.
      burgdorferi-infected, IL-10-deficient mice. Taken together, these findings
      provide additional evidence of a role for IL-17 in Lyme arthritis and reveal an
      additional regulatory target of IL-10 following borrelial infection. 

PMID- 24042117
TI  - Cell death of gamma interferon-stimulated human fibroblasts upon Toxoplasma
      gondii infection induces early parasite egress and limits parasite replication.
AB  - The intracellular protozoan parasite Toxoplasma gondii is a major food-borne
      illness and opportunistic infection for the immunosuppressed. Resistance to
      Toxoplasma is dependent on gamma interferon (IFN-gamma) activation of both
      hematopoietic and nonhematopoietic cells. Although IFN-gamma-induced innate
      immunity in nonhematopoietic cells has been extensively studied in mice, it
      remains unclear what resistance mechanisms are relied on in nonhematopoietic
      human cells. Here, we report an IFN-gamma-induced mechanism of resistance to
      Toxoplasma in primary human foreskin fibroblasts (HFFs) that does not depend on
      the deprivation of tryptophan or iron. In addition, infection is still controlled
      in HFFs deficient in the p65 guanylate binding proteins GBP1 or GBP2 and the
      autophagic protein ATG5. Resistance is coincident with host cell death that is
      not dependent on the necroptosis mediator RIPK3 or caspases and is correlated
      with early egress of the parasite before replication. This IFN-gamma-induced cell
      death and early egress limits replication in HFFs and could promote clearance of
      the parasite by immune cells. 

PMID- 24042118
TI  - Trimeric autotransporter DsrA is a major mediator of fibrinogen binding in
      Haemophilus ducreyi.
AB  - Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital
      ulcer disease chancroid. In both natural and experimental chancroid, H. ducreyi
      colocalizes with fibrin at the base of the ulcer. Fibrin is obtained by cleavage
      of the serum glycoprotein fibrinogen (Fg) by thrombin to initiate formation of
      the blood clot. Fg binding proteins are critical virulence factors in medically
      important Gram-positive bacteria. H. ducreyi has previously been shown to bind Fg
      in an agglutination assay, and the H. ducreyi Fg binding protein FgbA was
      identified in ligand blotting with denatured proteins. To better characterize the
      interaction of H. ducreyi with Fg, we examined Fg binding to intact, viable H.
      ducreyi bacteria and identified a novel Fg binding protein. H. ducreyi bound
      unlabeled Fg in a dose-dependent manner, as measured by two different methods. In
      ligand blotting with total denatured cellular proteins, digoxigenin (DIG)-Fg
      bound only two H. ducreyi proteins, the trimeric autotransporter DsrA and the
      lectin DltA; however, only the isogenic dsrA mutant had significantly less cell
      associated Fg than parental strains in Fg binding assays with intact bacteria.
      Furthermore, expression of DsrA, but not DltA or an empty vector, rendered the
      non-Fg-binding H. influenzae strain Rd capable of binding Fg. A 13-amino-acid
      sequence in the C-terminal section of the passenger domain of DsrA appears to be
      involved in Fg binding by H. ducreyi. Taken together, these data suggest that the
      trimeric autotransporter DsrA is a major determinant of Fg binding at the surface
      of H. ducreyi. 

PMID- 24042119
TI  - Loss of mitochondrial protein Fus1 augments host resistance to Acinetobacter
      baumannii infection.
AB  - Fus1 is a tumor suppressor protein with recently described immunoregulatory
      functions. Although its role in sterile inflammation is being elucidated, its
      role in regulating immune responses to infectious agents has not been examined.
      We used here a murine model of Acinetobacter baumannii pneumonia to identify the
      role of Fus1 in antibacterial host defenses. We found that the loss of Fus1 in
      mice results in significantly increased resistance to A. baumannii pneumonia. We
      observed earlier and more robust recruitment of neutrophils and macrophages to
      the lungs of infected Fus1(-/-) mice, with a concomitant increase in phagocytosis
      of invading bacteria and more rapid clearance. Such a prompt and enhanced immune
      response to bacterial infection in Fus1(-/-) mice stems from early activation of
      proinflammatory pathways (NF-kappaB and phosphatidylinositol 3
      kinase/Akt/mammalian target of rapamycin [mTOR]), most likely due to
      significantly increased mitochondrial membrane potential and mitochondrial
      reactive oxygen species production. Significant early upregulation of interleukin
      17 (IL-17) in Fus1(-/-) immune cells was also observed, together with significant
      downregulation of IL-10. Depletion of neutrophils eliminates the enhanced
      antibacterial defenses of the Fus1(-/-) mice, suggesting that ultimately it is
      the enhanced immune cell recruitment that mediates the increased resistance of
      Fus1(-/-) mice to A. baumannii pneumonia. Taken together, our data define the
      novel role for Fus1 in the immune response to A. baumannii pneumonia and
      highlight new avenues for immune modulating therapeutic targets for this
      treatment-resistant nosocomial pathogen. 

PMID- 24042120
TI  - FimY does not interfere with FimZ-FimW interaction during type 1 fimbria
      production by Salmonella enterica serovar Typhimurium.
AB  - The production of type 1 fimbriae in Salmonella enterica serovar Typhimurium is
      controlled, in part, by three proteins, FimZ, FimY, and FimW. Amino acid sequence
      analysis indicates that FimZ belongs to the family of bacterial response
      regulators of two-component systems. In these studies, we have demonstrated that
      introducing a mutation mimicking phosphorylation of FimZ is necessary for
      activation of its target gene, fimA. In addition, the interaction of FimZ with
      FimW, a repressor of fimA expression, occurs only when FimZ is phosphorylated.
      Consequently, the negative regulatory effect of FimW is most likely due to
      downmodulation of the active FimZ protein. FimY does not appear to function as a
      response regulator, and its activity can be lost by mimicking the phosphorylation
      of FimY. Overproduction of FimY cannot alleviate the nonfimbriate phenotype in a
      FimZ mutant, whereas high levels of FimZ can overcome the nonfimbriate phenotype
      of a FimY mutant. It appears that FimY acts upstream of FimZ to activate fimA
      expression. 

PMID- 24042121
TI  - Optimization and validation of DNA extraction and real-time PCR assay for the
      quantitative measurement of residual host cell DNA in biopharmaceutical products.
AB  - Host cell DNA contamination occurs during the production of biopharmaceuticals
      and must be controlled and monitored for the purity and safety of the drug
      products. A sodium iodide-based DNA extraction and a subsequent real time PCR
      assay were developed and validated for the quantitative measurement of residual
      host cell DNA impurity in monoclonal antibody therapeutic products. A sodium
      iodide-based commercial kit was optimized for the removal of interfering
      matrices. Several incubation steps from the kit protocol were combined and a
      neutralization buffer was introduced to protein digestion step to eliminate any
      precipitation from the detergent. The elimination of the two washing steps
      significantly reduced assay variability from loss of DNA pellets. The optimized
      DNA extraction procedure can recover DNA close to 100% for DNA concentrations
      from 10 to 100,000pg/mL. Of the published sequences of repetitive interspersed
      nuclear elements, we identified a nucleotide mismatch from the published CHO
      probe. Correction of this nucleotide increased DNA amplification by a thousand
      fold. The optimized assay was further validated for the quantitation of residual
      CHO DNA according to ICH guidelines with preset assay acceptance criteria. The
      method met all assay acceptance criteria and was found linear, accurate and
      precise for the quantitation of residual CHO in the linear range of 10-100,000pg
      DNA/mL. LOQ was measured at 10pg DNA/mL and LOD at 1pg DNA/mL. No matrix
      interference to our validated assay was detected from bioreactor harvest, Protein
      A eluate or eluate from ion exchange columns. 

PMID- 24042122
TI  - Metabolism studies of ifenprodil, a potent GluN2B receptor antagonist.
AB  - The NMDA receptor antagonist ifenprodil is an important lead structure for
      developing new GluN2B selective NMDA receptor antagonists. Ifenprodil itself has
      a high affinity to the GluN2B subunit but a poor selectivity for the NMDA
      receptor. This aspect and the fast biotransformation are the major drawbacks of
      ifenprodil. In order to optimize the development of new and more selective GluN2B
      (NMDA) receptor antagonists, the identification of the main metabolic pathways of
      ifenprodil is necessary. Herein the in vitro and in vivo phase I and phase II
      metabolites of ifenprodil were generated and analyzed via LC-MS(n) experiments.
      In vitro experiments were carried out with rat liver microsomes and various co
      factors to generate phase I and phase II metabolites. The application of
      ifenprodil to a rat and the analysis of its urine led to the identification of
      diverse formed in vivo metabolites. The phenol represents the metabolically most
      labile structural element since glucuronide 7 and 8 appeared as main metabolites.

PMID- 24042124
TI  - Verbal memory after epilepsy surgery in childhood.
AB  - PURPOSE: To investigate verbal memory after epilepsy surgery both group-wise and
      at the level of individual children, and to assess associations with side of
      surgery and removal of the temporal lobe. METHODS: A prospective controlled study
      in a consecutive sample of 21 children undergoing epilepsy surgery, with
      comprehensive assessments of verbal memory before surgery and six, 12 and 24
      months after surgery. For each patient, two age- and gender-matched controls were
      tested at similar intervals. Standardized regression-based (SRB) analysis was
      applied to compare post-surgical change in individual patients with change in
      controls. RESULTS: Group-wise, average normed scores on verbal memory tests were
      higher after epilepsy surgery than before, corroborating earlier reports. By dint
      of empirically based SRB analysis, however, considerable individual differences
      in post-surgical change were revealed. Children with resections that included the
      left temporal lobe functioned significantly poorer than predicted on the basis of
      their pre-surgical performance. In contrast, verbal memory performance after
      surgery was consistent with pre-surgical baseline in the majority of children
      with resections that spared the left temporal lobe. CONCLUSIONS: Despite
      cessation of epileptic seizures, verbal memory remains vulnerable in children who
      required surgery including the left temporal lobe. In most - but not all -
      children with other types of surgery, post-surgical verbal memory is consistent
      with their individual pre-surgical base level.

PMID- 24042123
TI  - Determination of androgen receptor degradation enhancer ASC-J9((r)) in mouse sera
      and organs with liquid chromatography tandem mass spectrometry.
AB  - A novel androgen receptor (AR) degradation enhancer ASC-J9((r)) has displayed
      beneficial effects during the in vitro and in vivo studies for treatment of
      prostate cancer, liver cancer, bladder cancer and spinal and bulbar muscular
      atrophy (SBMA). It works mainly via the degradation of AR with minimal side
      effects on the tested mice. Here we developed a fast, robust and more sensitive
      method for the quantification of ASC-J9((r)) in 100MUL of mouse serum by using
      liquid chromatography tandem mass spectrometry (LC-MS/MS). The limit of
      quantification (LOQ) was found to be 5nM for ASCJ9((r)). This method was
      successfully applied to investigate the pharmacokinetics of ASC-J9((r)) in mice
      serum samples and also the distribution of the drug in various mice organs after
      single dose injection with results showing that ASC-J9((r)) could be quickly
      absorbed in vivo and had a relatively slow elimination half-life of 5.45h. The
      ASC-J9((r)) also exhibited a higher tendency to accumulate in organs such as
      liver, testes and prostate. 

PMID- 24042125
TI  - Macular ganglion cell complex thickness in glaucoma with superior or inferior
      visual hemifield defects.
AB  - PURPOSE: To elucidate the relationship between the macular ganglion cell complex
      thickness (GCCT) and its corresponding superior or inferior visual hemifield
      defects, and the apparently normal visual hemifield, and to explore the
      relationship between the macular GCCT of the corresponding apparently normal
      hemifield and the severity of the glaucomatous visual field defects in the same
      eye. METHODS: Sixty-seven eyes of 67 patients with open-angle glaucoma showed
      superior or inferior hemifield defects. We measured the visual field using the
      Humphrey Field Analyzer programs Central 30-2 and 10-2, and the GCCT using
      spectral domain optical coherence tomography. For the GCCT measurement, we
      selected 3 points each in the inner or outer sectors of the parafovea. RESULTS:
      We observed a significant correlation between the macular GCCT of the inner or
      outer sector of the parafovea and in the change of the visual field in each
      hemifield defect or the apparently normal hemifield. The decrease of the GCCT
      corresponding to the apparently normal hemifield correlated with the progression
      of the severity of the glaucomatous defects, using the Anderson classification.
      CONCLUSIONS: The macular GCCT is a sensitive marker of early glaucomatous change,
      allowing detection of structural changes associated with glaucoma even in the
      apparently normal hemifield.

PMID- 24042126
TI  - The effect of ABCB1 C3435T polymorphism on pharmacokinetics of tacrolimus in
      liver transplantation: a meta-analysis.
AB  - OBJECTIVES: The effect of ABCB1 C3435T SNP on the pharmacokinetics of
      immunosuppressive drug tacrolimus in different studies was conflicting. So a meta
      analysis was employed to study the correlation of ABCB1 C3435T SNP and the
      pharmacokinetics of tacrolimus at different post-transplantation times. METHOD:
      Several studies about ABCB1 C3435T polymorphism and the pharmacokinetics of
      tacrolimus were collected through the search on PubMed and the Cochrane Library.
      After the extraction of pharmacokinetic parameters from these studies, a meta
      analysis was performed on the software STATA version 11.0. RESULTS: A total of 9
      studies were adopted including 558 liver transplant recipients. For the dose of
      tacrolimus, the subjects with wild-type CC had a significantly higher tacrolimus
      dose than homozygous mutated genotype TT within 1 week (WMD=0.01 (0.00, 0.02),
      P=0.014) and the similar result in recipients with heterozygous CT compared with
      TT after transplantation for 1 month (WMD=0.01 (0.00, 0.02), P=0.002). For the
      tacrolimus concentration/dose ratio, subjects with CT had higher C/D ratio than
      those with CC and TT at different post-transplantation times. A subgroup analysis
      based on different ethnic populations was also carried out. Donors' genotypes
      were also considered in this meta-analysis. CONCLUSION: Through this meta
      analysis for the including studies about the pharmacokinetics of tacrolimus and
      ABCB1 C3435T SNP, several significant associations were obtained. Particularly,
      the Caucasians showed more significant associations between the C/D ratio and
      ABCB1 C3435T polymorphism; however, the correlations were not steady at different
      post-transplantation times.

PMID- 24042127
TI  - Fundamental role of start/stop regulators in whole DNA and new trinucleotide
      classification.
AB  - The origin and logic of genetic code are two of greatest mysteries of life
      sciences. Analyzing DNA sequences we showed that the start/stop trinucleotides
      have broader importance than just marking start and stop of exons in coding DNA.
      On this basis, here we introduced new classification of trinucleotides and showed
      that all A+T rich trinucleotides consisting of three different nucleotides arise
      from start-ATG, stop-TGA and stop-TAG using their complement, reverse complement
      and reverse transformations. Due to the same transformations during generations
      of crossing-over they can switch from one form to the other. By direct process
      the start-ATG and stop-TAG can irreversibly transform into stop-TAA. By
      transformation into A+T rich trinucleotides and 16/32 C+G rich they can lose the
      start/stop function and take the role of a sense codon in reversible way. The
      remaining 16 C+G trinucleotides cannot directly transform into start/stop
      trinucleotides and thus remain a firm skeleton for structuring the C+G rich DNA.
      We showed that start/stops strongly enrich the A+T rich noncoding DNA through
      frequently extended forms. From the evolutionary viewpoint the start/stops are
      chief creators of prevailing A+T rich noncoding DNA, and of more stable coding
      DNA. We propose that start/stops have basic role as "seeds" in trinucleotide
      evolution of noncoding and coding sequences and lead to asymmetry between A+T and
      C+G rich DNA. By dynamical transformations during evolution they enabled
      pronounced phylogenetic broadness, keeping the regulator function. 

PMID- 24042128
TI  - Predicting distinct organization of transcription factor binding sites on the
      promoter regions: a new genome-based approach to expand human embryonic stem cell
      regulatory network.
AB  - Self-proliferation and differentiation into distinct cell types have been made
      stem cell as a promising target for regenerative medicine. Several key genes can
      regulate self-renewal and pluripotency of embryonic stem cells (hESCs). They work
      together and build a transcriptional hierarchy. Coexpression and coregulation of
      genes control by common regulatory elements on the promoter regions.
      Consequently, distinct organization and combination of transcription factor
      binding sites (TFBSs modules) on promoter regions, in view of order and distance,
      lead to a common specific expression pattern within a set of genes. To gain
      insights into transcriptional regulation of hESCs, we selected promoter regions
      of eleven common expressed hESC genes including SOX2, LIN28, STAT3, NANOG, LEFTB,
      TDGF1, POU5F1, FOXD3, TERF1, REX1 and GDF3 to predict activating regulatory
      modules on promoters and discover key corresponding transcription factors. Then,
      promoter regions in human genome were explored for modules and 328 genes
      containing the same modules were detected. Using microarray data, we verified
      that 102 of 328 genes commonly upregulate in hESCs. Also, using output data of
      DNA-protein interaction assays, we found that 42 of all predicted genes are
      targets of SOX2, NANOG and POU5F1. Additionally, a protein interaction network of
      hESC genes was constructed based on biological processes, and interestingly, 126
      downregulated genes along with upregulated ones identified by promoter analysis
      were predicted in the network. Based on the results, we suggest that the
      identified genes, coregulating with common hESC genes, represent a novel approach
      for gene discovery based on whole genome promoter analysis irrespective of gene
      expression. Altogether, promoter profiling can be used to expand hESC
      transcriptional regulatory circuitry by analysis of shared functional sequences
      between genes. This approach provides a clear image on underlying regulatory
      mechanism of gene expression profile and offers a novel approach in designing
      gene networks of stem cell.

PMID- 24042129
TI  - Genetic risk assessment for cardiovascular disease in Azoreans (Portugal): a
      general population-based study.
AB  - The identification of clinically validated genetic variants contributing to
      complex disorders raise the possibility to investigate individuals' risk. In this
      line of research, the present work aimed to assess the genetic risk for
      cardiovascular disease (CVD) in Azoreans. Genotyping of 19 SNPs - 9 on 9p21, 5 on
      LDLR and 5 on USF1 - was performed by TaqMan assays on 170 healthy Azorean
      individuals. Results demonstrate that the most frequent haplotype in 9p21, with a
      frequency of 41.4%, is TGGGCGCGC, which harbors all risk alleles. Considering
      haplotype homozygosity data show that females present higher value of
      homozygosity for both LDLR (13.5%) and USF1 (15.3%), whereas males present higher
      value for the 9p21 region (8.2%). Interestingly, genetic profile analysis
      revealed differences in terms of geographic and gender distribution. The Azorean
      Central group presented a higher risk for atherosclerosis, 2.7 times higher when
      compared to the Eastern group, while the Eastern group shows 1.5 times higher
      risk for dyslipidemias. Moreover, Azorean females demonstrated a 4 times higher
      risk for dyslipidemias when compared to males, whereas males have an increased
      risk for atherosclerosis. Although allele frequencies in Azoreans were similar to
      those reported for the HapMap CEU population, the differences in terms of
      haplotype and genetic profile distribution must be taken in consideration when
      assessing genetic risk. Taken together, the data here presented evidence for the
      need to perform biomedical research and epidemiologic analysis in Azoreans with
      the aim of developing strategies to CVD prevention, health promotion and
      population education. 

PMID- 24042131
TI  - What is professionalism?

PMID- 24042130
TI  - A collection of glycosyltransferases from rice (Oryza sativa) exposed to
      atrazine.
AB  - The rice (Oryza sativa) GTs belong to a super family possibly with hundreds of
      members. However, which GTs are involved in plant response to toxic chemicals is
      unknown. Here, we demonstrated 59 novel GT genes screened from our recent genome
      wide sequencing datasets of rice crops exposed to atrazine (a herbicide
      persistent in ecosystems). Analysis of GT genes showed that most of the GTs
      contain functional domains typically found in proteins transferring glycosyl
      moieties to their target compounds. A phylogenetic analysis revealed that many GT
      genes from different families have diverse cis-elements necessary for response to
      biotic and environmental stresses. Experimental validation for the GTs was
      undertaken through a microarray, and 36 GT genes were significantly detected with
      an expression pattern similar to that from deep-sequencing datasets. Furthermore,
      12 GT genes were randomly selected and confirmed by quantitative real-time RT
      PCR. Finally, the special activity of total GTs was determined in rice roots and
      shoots, with an increased activity under the atrazine exposure. This response was
      closely associated with atrazine absorption in the rice tissues. These results
      indicate that exposure to atrazine can trigger specific GT genes and enzyme
      activities in rice. 

PMID- 24042132
TI  - NANN discusses bullying in the workplace, educational abstract deadlines, and the
      NNP Workforce Survey.

PMID- 24042134
TI  - Occlusive bags to prevent hypothermia in premature infants: a quality improvement
      initiative.
AB  - The aim of this quality improvement initiative was to improve the neonatal
      intensive care unit (NICU) admission rectal temperatures of premature infants
      less than 28 weeks' gestation by placing them in an occlusive bag from the neck
      down immediately after birth. The historical control group consisted of a
      convenience sample of 46 very low-birth-weight infants from March 1, 2010, to
      August 31, 2010. A convenience sample of 35 very low-birth-weight infants from
      October 1, 2010, to April 30, 2011, was recruited during the prospective phase. A
      quasi-experimental design was used. A retrospective medical record review was
      performed to collect data on NICU admission rectal temperatures for the
      historical control group. During the prospective phase, infants were placed in a
      bag from the neck down immediately after birth and NICU admission rectal
      temperatures were recorded. In both groups, NICU rectal temperatures were
      measured immediately upon admission. Application of the bag resulted in a higher
      mean NICU admission rectal temperature in the intervention group compared with
      the historical control group. Occlusive bags applied at delivery decreased heat
      loss in premature infants. The results support previous findings and resulted in
      a change in clinical practice. 

PMID- 24042135
TI  - Necrotizing enterocolitis: have we made any progress in reducing the risk?
AB  - Necrotizing enterocolitis (NEC) is a disease affecting premature infants with
      potentially devastating complications in the neonatal intensive care unit (NICU).
      Inadequate knowledge regarding the underlying pathophysiology of this disease has
      contributed to the minimal progress made in decreasing the incidence and severity
      of NEC. Because of an improved survival rate of the most immature infants, the
      number of diagnosed cases of NEC is anticipated to increase. Unfortunately,
      decades of research have failed to reduce the risk or improve the prognosis of
      NEC, magnifying the need for risk-reduction strategies for decreasing significant
      NEC-related morbidity and mortality. Advancements in our understanding of this
      disease process have facilitated the development of several strategies that have
      been investigated in the risk reduction of NEC. This article discusses the
      pathophysiology and causes of NEC and presents strategies investigated regarding
      risk reduction of this devastating disease. 

PMID- 24042137
TI  - Professional boundaries: communication after patient discharge.
AB  - The blurring of professional boundaries commonly takes place when a nurse cares
      for a patient for an extended period of time. This article focuses on the aspects
      of professional boundaries in neonatal nursing, particularly in regard to
      communication after patient discharge. Modes of caring are investigated to
      understand the nature of the therapeutic relationship between nurse and patient
      and how this can present an ethical dilemma at the end of a patient's hospital
      stay. A discussion of how a patient reunion is organized is discussed at the end
      of this article as a possible solution to reconnecting patient-nurse ties in a
      professional manner. 

PMID- 24042138
TI  - Considering boundaries in nursing: what the staff nurse needs to know.
AB  - This article considers the ethics of boundaries and nursing practice. The nurse's
      role as a "carer" is reflected in the context of boundary setting, boundary
      crossing, and boundary violation. This issue is redeveloped within the new
      perspective of the nurse's use of social media and boundary crossing. National
      and international regulations are discussed and individual cases assessed. The
      Nurses Code of Ethics is used as a framework. The American Nurses Association
      material on social media is reviewed. 

PMID- 24042139
TI  - Implementing family-integrated care in the NICU: educating nurses.
AB  - The purpose of this study was to develop, implement, and evaluate a nursing
      education program to support family-integrated care in a Canadian neonatal
      intensive care unit (NICU). A total of 44 nurses volunteered to take part in the
      family-integrated care program, 35 of whom received additional education in the
      form of a 4-hour workshop. Of the 35 nurses who attended, 21 were interviewed
      regarding the impact and content of the workshop. The study design included the
      development, implementation, and qualitative assessment of the nursing education
      component of a family-integrated care program. The multidisciplinary program team
      conducted a literature review and then designed and conducted a survey to assess
      the educational requirements of nurses regarding family-integrated care. A
      nursing workshop was then developed on the basis of the literature review, staff
      survey responses, and discussions with staff and parents who had experienced
      having an infant in the NICU. Six months into the program, the contribution of
      the nursing workshop content to nurses' participation in the family-integrated
      care program was evaluated using individual structured interviews. Nurses who
      were interviewed described the workshop as valuable and reported that the
      information provided on nursing versus parental responsibilities in infant care,
      the parent experience in the NICU, and developmental care strategies was the most
      useful. Interviewees also identified the need for ongoing staff mentoring to
      maximize their ability to facilitate family-integrated care. Specific education
      for nurses facilitates family-integrated care in the NICU. 

PMID- 24042140
TI  - Concept analysis of mentoring.
AB  - The purpose of a concept analysis is to examine the structure and function of a
      concept by defining its attributes and internal structure. Concept analysis can
      clarify an overused or vague concept and promote mutual understanding by
      providing a precise operational definition. Mentoring is a concept more fully
      used by other fields, such as business, than in nursing and may not always
      translate well for use in nursing. Therefore, clarifying the meaning of the
      existing concept of mentoring and developing an operational definition for use in
      nursing are aims of this concept analysis. Mentoring is broadly based and
      concentrates on developing areas such as career progression, scholarly
      achievements, and personal development. Mentoring relationships are based around
      developing reciprocity and accountability between each partner. Mentoring is seen
      related to transition in practice, role acquisition, and socialization, as a way
      to support new colleagues. Mentorship is related to nurses' success in nursing
      practice linked to professionalism, nursing quality improvement, and self
      confidence. 

PMID- 24042141
TI  - State of the state: NNP program update 2013.
AB  - Findings from a spring 2013 survey of neonatal nurse practitioner (NNP) program
      directors are presented and concerning trends identified. Implications of these
      findings, in combination with other external factors influencing the
      supply/demand ratio on the stability of the NNP workforce nationwide, are
      explored. Present and future NNP workforce demands in relation to the educational
      programs available to prepare nurses for NNP practice are examined. Finally,
      discussion focuses on the politics and pragmatics of sustaining the NNP role for
      posterity. 

PMID- 24042142
TI  - Music therapy in the NICU: is there evidence to support integration for
      procedural support?

PMID- 24042143
TI  - Neonatal nurses' perceptions of pain assessment and management in NICUs: a
      national survey.
AB  - PURPOSE: The purpose of this survey was to investigate neonatal nurses'
      perceptions of knowledge and practice in pain assessment and management. METHODS:
      A convenience sample consisted of 237 neonatal nurses with a membership in
      National Association of Neonatal Nurses (NANN) and neonatal nurses in Connecticut
      who were not NANN members. A researcher-developed questionnaire, including 36
      questions with Likert scale and 2 open-ended questions, was used. RESULTS: The
      nurses were knowledgeable, and about 50% felt that they received adequate
      training and continuing education on pain. Participants reported the use of pain
      assessment tools (81%) and felt confident in uses of pharmacologic (83%) and
      nonpharmacologic interventions (79%). More than half felt that the pain tool used
      in their unit was appropriate for neonates (65%) and was an accurate measure
      (60%). Fewer than half reported that pain was well managed (44%) and that their
      pain protocols were research evidence based (43%). CONCLUSIONS: Nurses'
      perceptions of well-managed pain were significantly correlated with training, use
      of appropriate and accurate pain tools, and clear and research-based protocols.
      Barriers to effective pain management emerged as resistance to change, lack of
      knowledge, perceived fear of side effects of pain medication and incorrect
      interpretation of pain signals, lack of time, and lack of trust in the pain
      assessment tools. Gaps exist in knowledge, evidence, and practice in neonatal
      assessment and management.

PMID- 24042144
TI  - Axillary temperatures in full-term newborn infants: using evidence to guide safe
      and effective practice.
AB  - PURPOSE: Although the American Academy of Pediatrics and the American Congress of
      Obstetricians and Gynecologists recommend obtaining temperature in newborn
      infants via the axilla, controversy still exists whether to obtain rectal or
      axillary temperatures. Of concern is the risk of perforating the rectum or colon
      during rectal temperature-taking. The purpose of this study was to explore the
      accuracy of electronic thermometer measuring temperature in the axilla compared
      with the rectum in full-term newborn infants. DESIGN: This was an agreement study
      involving a purposive sample of newborn infants who were greater than 37 weeks'
      gestation. The general care nursery was located in a large, urban Midwestern
      academic medical center, and data collection occurred between May 2010 and August
      2010. METHODS: On admission to the general care nursery, both axillary and rectal
      temperatures were taken using the FasTemp device by Filac Electronic. Axillary
      temperatures were taken first, followed immediately by rectal temperature.
      Descriptive statistics, Pearson correlations, and scatter plots were computed.
      RESULTS: In 69 newborns, the mean difference between rectal and left axilla
      temperatures was 0.23 degrees C. There was a significant correlation between
      rectal temperature and the body temperature for the left axilla (r = 0.786; P =
      .01). CONCLUSIONS: These preliminary data support the use of left axillary
      temperature measurement in the full-term newborn infant in the first few days of
      life to provide a safe and accurate alternative to rectal temperatures. CLINICAL
      RELEVANCE: Nurses caring for newborn infants now have evidence showing that
      temperature-taking in the left axilla is an alternative to using rectal
      temperatures, possibly minimizing discomfort and potential risk of perforation.

PMID- 24042145
TI  - Nurses' perception of milk temperature at delivery compared to actual practice in
      the neonatal intensive care unit.
AB  - PURPOSE: The purposes of this study were to examine nurses' perception of feeding
      temperature practices and to compare the nurses' temperature estimation with the
      measured temperature of milk at the time of delivery to the infant. DESIGN: A
      descriptive exploratory study was conducted in 3 level III neonatal intensive
      care units (NICUs). SUBJECTS: A convenience sample of nurses from 3 level III
      NICUs in the Midwest. In addition, temperatures from bottle/syringe samples of
      formula/breast milk were measured and recorded. METHODS: The Feeding Practices
      and Temperature Survey, a 10-item survey measuring nurses' perception of the
      effect of feeding temperature on infant condition, was distributed to subjects.
      Afterward for select feedings, researchers recorded the type of milk, delivery
      method, nurses' estimated temperature of the milk, and the measured infrared
      temperature of milk just before feeding delivery. To compare perception with
      actual practice patterns, the measured milk temperature was compared with the
      nurses' estimated temperature, standard room temperature, and body temperature
      using descriptive statistics of the survey responses and t test comparisons. MAIN
      OUTCOME MEASURES/PRINCIPAL RESULTS: A total of 141 surveys were analyzed. More
      than 50% of respondents reported feeding temperature as clinically very
      significant. A range of 35.5 degrees C to 37.2 degrees C was reported as the
      ideal temperature of breast milk at delivery. Recordings of 419 temperatures were
      used for analysis. Measured milk temperature just before feeding ranged from 22
      degrees C to 46.4 degrees C. The mean measured temperatures were 31.0 degrees C
      (SD = 2.8 degrees C) for warmed milk in a bottle and 30.5 degrees C (SD = 2.5
      degrees C) for milk warmed in a syringe. The measured milk temperature and the
      nurse-estimated temperature were significantly lower than body temperature (P =
      0.000) and significantly higher than room temperature (P = 0.000). CONCLUSION:
      Current warming methods yield wide variation in milk temperature. Nurses'
      estimation of milk temperature was not consistent with measured temperature at
      the time of delivery. Future research is needed to establish guidelines for
      feeding temperature standardization assisting nurses to enhance evidence-based
      feeding practices.

PMID- 24042146
TI  - Hydrogenosomes in the diplomonad Spironucleus salmonicida.
AB  - Acquisition of the mitochondrion is a key event in the evolution of the
      eukaryotic cell, but diversification of the organelle has occurred during
      eukaryotic evolution. One example of such mitochondria-related organelles (MROs)
      are hydrogenosomes, which produce ATP by substrate-level phosphorylation with
      hydrogen as a byproduct. The diplomonad parasite Giardia intestinalis harbours
      mitosomes, another type of MRO. Here we identify MROs in the salmon parasite
      Spironucleus salmonicida with similar protein import and Fe-S cluster assembly
      machineries as in Giardia mitosomes. We find that hydrogen production is
      prevalent in the diplomonad genus Spironucleus, and that S. salmonicida MROs
      contain enzymes characteristic of hydrogenosomes. Evolutionary analyses of known
      hydrogenosomal components indicate their presence in the diplomonad ancestor, and
      subsequent loss in Giardia. Our results suggest that hydrogenosomes are metabolic
      adaptations predating the split between parabasalids and diplomonads, which is
      deeper than the split between animals and fungi in the eukaryotic tree. 

PMID- 24042147
TI  - Metallic stents for airway complications after lung transplantation: long-term
      follow-up.
AB  - OBJECTIVES: Bronchial stenosis is still a significant source of morbidity and
      mortality following lung transplantation (LTX) and often mandating placement of a
      bronchial stent. It has been suggested that although self-expanding metal stents
      offer excellent early palliation, their long-term complication rates are
      unacceptably high, and hence, their usage in many transplantation centres has
      been nearly abandoned. The aim of the study was to assess short- and long-term
      complication rates and survival in LTX patients with bronchial stenosis treated
      with insertion of self-expanding metal stents. METHODS: From January 1997 to
      March 2013, 435 patients underwent LTX (325 single-LTX and 110 bilateral LTX). Of
      503 actual anastomoses at risk (derived by subtracting the number of anastomoses
      in 30 patients who died within 30 days of LTX), 60 airway complications (11.9%)
      in 47 patients required self-expanding metal stent insertion. We assessed the
      early results and long-term outcomes and survival compared with LTX patients in
      whom stents were not required. RESULTS: The median follow-up period ranged from 1
      to 132 (median 54) months. Immediate relief of symptoms was achieved in the vast
      majority of patients (95%). One-, three- and five-year survival in patients who
      required self-expanding metal stent placement were 77.7, 66.6 and 55.5%,
      respectively. The corresponding survival rates in LTX patients without stents
      were 69, 64.9 and 61.1% (P > 0.05). CONCLUSIONS: Self-expanding metal stents are
      safe and effective tools in the management of airway complications post-LTX and
      provide immediate improvement in symptoms and pulmonary function tests in the
      vast majority of cases. The long-term complication rate is low, and mortality is
      similar to that in LTX patients who did not require stent insertion.

PMID- 24042148
TI  - A highly cytotoxic modified paullone ligand bearing a TEMPO free-radical unit and
      its copper(II) complex as potential hR2 RNR inhibitors.
AB  - A new paullone-TEMPO conjugate and its copper(II) complex inhibit RNR activity
      and show high antiproliferative activity in human cancer cell lines.

PMID- 24042151
TI  - If you say PEEP, I say how high?

PMID- 24042150
TI  - Atomic scale verification of oxide-ion vacancy distribution near a single grain
      boundary in YSZ.
AB  - This study presents atomic scale characterization of grain boundary defect
      structure in a functional oxide with implications for a wide range of
      electrochemical and electronic behavior. Indeed, grain boundary engineering can
      alter transport and kinetic properties by several orders of magnitude. Here we
      report experimental observation and determination of oxide-ion vacancy
      concentration near the Sigma13 (510)/[001] symmetric tilt grain-boundary of YSZ
      bicrystal using aberration-corrected TEM operated under negative spherical
      aberration coefficient imaging condition. We show significant oxygen deficiency
      due to segregation of oxide-ion vacancies near the grain-boundary core with half
      width < 0.6 nm. Electron energy loss spectroscopy measurements with scanning TEM
      indicated increased oxide-ion vacancy concentration at the grain boundary core.
      Oxide-ion density distribution near a grain boundary simulated by molecular
      dynamics corroborated well with experimental results. Such column-by-column
      quantification of defect concentration in functional materials can provide new
      insights that may lead to engineered grain boundaries designed for specific
      functionalities. 

PMID- 24042152
TI  - The need for networking in sepsis research: a must to move forward.

PMID- 24042153
TI  - Evaluation of acid-base status in brain dead donors and the impact of metabolic
      acidosis on organ retrieval.
AB  - BACKGROUND: Pathophysiologic changes after brain death can lead to acid-base
      disturbances. The primary aim of this study was to clarify the acid-base state
      and its source in brain dead donors using Stewart's approach. Additionally, we
      investigated whether the presence of metabolic acidosis affected the number of
      organs retrieved from donors. METHODS: A retrospective review of electronic
      medical records was performed for brain dead donors who had undergone organ
      harvesting during the past 5 years in a tertiary medical center. The parameters
      related to acid-base disturbance and the number of organs retrieved from the
      donors was assessed. RESULTS: Sixty one brain dead donors were evaluated in this
      study. Twenty three (37.7%) of these patients had metabolic acidosis at the
      initial diagnosis of brain death. Metabolic acidosis resulted from hyperchloremia
      and a large strong ion gap. The severity of metabolic acidosis was masked by
      hypernatremia and hypoalbuminemia. In addition, donors without metabolic acidosis
      also showed mixed acid-base disturbances in which metabolic acidosis induced by
      significant hyperchloremia was combined with metabolic alkalosis caused by
      hypoalbuminemia and hypernatremia. Although more organs were retrieved from the
      donors without metabolic acidosis than those with metabolic acidosis (P=0.012),
      serum albumin level (P=0.010) and donor age (P<0.001), rather than metabolic acid
      base disturbances, significantly correlated with the number of organs retrieved
      in multivariate regression analysis. CONCLUSION: Most brain dead donors exhibited
      metabolic acid-base disturbances. However, rather than metabolic acidosis, serum
      albumin level and donor age were well correlated with the number of organs
      retrieved.

PMID- 24042154
TI  - Lactate or ScvO2 as an endpoint in resuscitation of shock states?
AB  - In the current management of critically ill patients, variables such as blood
      pressure, urine output or central venous pressure guide resuscitative efforts.
      Unfortunately, global tissue hypoxia may persist leading to multiple organ
      failure and death. To address tissue well-being, indices such as central venous
      oxygen saturation (ScvO2) and Lactatemia are widely used and are strongly linked
      to outcome. Implementing these indices in haemodynamic optimization protocols
      have been shown to reduce morbidity and mortality in numerous studies especially
      in septic shock. Nevertheless, choosing one index over the other remains
      controversial. Herein, we review the physiology and rationale for ScvO2 and
      lactate monitoring. Clinical uses, evidence-based outcome implications and
      limitations are also examined to aid the clinician in daily practice. 

PMID- 24042155
TI  - Infusion of hydroxyethyl starch-containing fluids.
AB  - The infusion of hydroxyethylstarch (HES) containing fluids has been extremely
      common worldwide over the last decade. Until recently, HES was probably the most
      commonly prescribed colloidal preparation in the world. Such prescription
      continued despite concerns that starch molecules might accumulate in vital organs
      and that starch preparations might decrease the coagulability of blood. These
      concerns have led to two pivotal multicenter double-blind controlled trials in
      critically ill patients, one conducted in Scandinavia in septic Intensive Care
      Unit (ICU) patients, and the other conducted in Australia and New Zealand in a
      heterogeneous group of ICU patients. Both studies found that the infusion of HES
      increased the risk of needing renal replacement therapy. In addition, the
      Scandinavian study found that HES increased mortality. Subsequent meta-analyses
      have confirmed these findings. In response to such strong evidence, over the last
      few weeks, the Food and Drug Administration has issued a major warning and, in
      Europe, the EMA suspended the marketing authorization for HES. At least in
      Europe, the clinical story of HES seems to have come to an end. 

PMID- 24042156
TI  - Effect of factor XIII-A Val34Leu polymorphism on myocardial infarction risk: a
      meta-analysis.
AB  - The association between factor XIII-A (FXIII-A) Val34Leu polymorphism and
      myocardial infarction (MI) risk remained controversial. We performed a meta
      analysis. Online databases were searched. Twenty-eight studies were included. The
      FXIII-A Val34Leu polymorphism was significantly associated with MI risk (odds
      ratio (OR) = 0.83, 95% confidence interval [CI] 0.76-0.91; P < .0001). This
      result remained statistically significant when the adjusted ORs were combined (OR
      = 0.77, 95% CI 0.65-0.92; P = .004). When stratifying for race, this polymorphism
      showed decreased MI risk in Caucasians. In the subgroup analysis by age group,
      significant associations were observed in early-onset patients and in late-onset
      patients. In the subgroup analysis by gender, there was a significant association
      in women but not in men. In the subgroup analysis stratified by smoking status,
      MI risk was decreased in both smokers and nonsmokers. This study suggested that
      FXIIIA Val34Leu polymorphism was a protective factor for MI in caucasians. 

PMID- 24042157
TI  - Haemostasis: Methods and Protocols. Methods in Molecular Biology.

PMID- 24042158
TI  - Consistency of peak and mean concentric and eccentric force using a novel squat
      testing device.
AB  - The ability to examine force curves from multiple-joint assessments combines many
      of the benefits of dynamic constant external resistance exercise and isokinetic
      dynamometry. The purpose of this investigation was to examine test-retest
      reliability statistics for peak and mean force using the Exerbotics eSQ during
      maximal concentric and eccentric squats. Seventeen resistance-trained men (mean+/
      SD age=21+/-2 years) visited the laboratory on two occasions. For each trial, the
      subjects performed two maximal concentric and eccentric squats, and the muscle
      actions with the highest force values were analyzed. There were no mean
      differences between the trials (P>.05), and the effect sizes were <0.12. When the
      entire force curve was examined, the intraclass correlation coefficients (model
      2,1) and standard errors of measurement, respectively, were concentric peak
      force=0.743 (8.8%); concentric mean force=0.804 (6.0%); eccentric peak
      force=0.696 (10.6%); eccentric mean force=0.736 (9.6%). These findings indicated
      moderate-to-high reliability for the peak and mean force values obtained from the
      Exerbotics eSQ during maximal squat testing. The analysis of force curves from
      multiple-joint testing provides researchers and practitioners with a reliable
      means of assessing performance, especially during concentric muscle actions.

PMID- 24042159
TI  - Effect of delay on self-administration of remifentanil under a drug versus drug
      choice procedure in rhesus monkeys.
AB  - Drug abuse can be conceptualized as excessive choice of drug over other
      reinforcers, and factors that affect drug taking can be examined experimentally
      using choice procedures. This study examined the impact of reinforcer delay on
      self-administration of the MU-opioid receptor agonist remifentanil in rhesus
      monkeys (n = 4) lever pressing under a concurrent fixed-ratio 30 schedule.
      Responding on either lever delivered an intravenous infusion of either
      remifentanil or saline. Dose-effect curves were first determined when responding
      on one lever delivered remifentanil and responding on a second lever delivered
      saline. Monkeys then chose between two doses of remifentanil, and delay to
      delivery of the large dose was varied systematically. Responding for remifentanil
      (0.01-1.0 ug/kg/infusion) increased dose-dependently when the alternative was
      saline or a dose of remifentanil. Delaying delivery of the large dose of
      remifentanil by 30, 60, 120, or 240 seconds increased responding for smaller,
      immediately available doses (0.01-0.1 ug/kg/infusion) and, in some cases,
      increased responding for doses of remifentanil that did not maintain responding
      when the alternative was saline. These data demonstrate that delaying the
      delivery of an opioid receptor agonist can significantly affect its reinforcing
      effectiveness. The imposition of a delay reduces the effectiveness of large doses
      of drug to maintain responding and increases the effectiveness of immediately
      available commodities, including smaller doses of drug. Increased reinforcing
      effectiveness of smaller doses of drug in the context of other delayed
      reinforcers might contribute to the development and maintenance of opioid abuse. 

PMID- 24042160
TI  - Translational studies of phenotypic probes for the mononuclear phagocyte system
      and liposomal pharmacology.
AB  - As nanoparticles (NPs) are cleared via phagocytes of the mononuclear phagocyte
      system (MPS), we hypothesized that the function of circulating monocytes and
      dendritic cells (MO/DC) in blood can predict NP clearance (CL). We measured MO/DC
      phagocytosis and reactive oxygen species (ROS) production in mice, rats, dogs,
      and patients with refractory solid tumors. Pharmacokinetic studies of
      polyethylene glycol (PEG)-encapsulated liposomal doxorubicin (PEGylated liposomal
      doxirubicin [PLD]), CKD-602 (S-CKD602), and cisplatin (SPI-077) were performed at
      the maximum tolerated dose. MO/DC function was also evaluated in patients with
      recurrent epithelial ovarian cancer (EOC) administered PLD. Across species, a
      positive association was observed between cell function and CL of PEGylated
      liposomes. In patients with EOC, associations were observed between PLD CL and
      phagocytosis (R(2) = 0.43, P = 0.04) and ROS production (R(2) = 0.61, P = 0.008)
      in blood MO/DC. These findings suggest that probes of MPS function may help
      predict PEGylated liposome CL across species and PLD CL in patients with EOC. 

PMID- 24042161
TI  - Differential long-term effects of haloperidol and risperidone on the acquisition
      and performance of tasks of spatial working and short-term memory and sustained
      attention in rats.
AB  - A common feature of the neuropsychiatric disorders for which antipsychotic drugs
      are prescribed is cognitive dysfunction, yet the effects of long-term
      antipsychotic treatment on cognition are largely unknown. In the current study,
      we evaluated the effects of long-term oral treatment with the first-generation
      antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation
      antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and
      performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction
      time task (5C-SRTT) in rats during days 15-60 and 84-320 days of treatment,
      respectively. In the RAM, neither antipsychotic significantly affected the
      acquisition or performance of a spatial win shift or a delayed non-match-to
      position task. Conversely, in the rats administered 5C-SRTT, haloperidol was
      associated with profound deficits in performance, and the subjects were not able
      to progress through all stages of task acquisition. Depending on the dose,
      risperidone was associated with a greater number of trials to meet specific
      performance criteria during task acquisition compared with vehicle-treated
      controls; however, most subjects were eventually able to achieve all levels of
      task acquisition. Both haloperidol and risperidone also increased the number of
      perseverative and time-out responses during certain stages of task acquisition,
      and the response and reward latencies were slightly higher than controls during
      several stages of the study. These results in rats suggest that while long-term
      treatment with haloperidol or risperidone may not significantly affect spatial
      working or short-term memory, both antipsychotics can (depending on dose) impair
      sustained attention, decrease psychomotor speed, increase compulsive-type
      behaviors, and impair cognitive flexibility. 

PMID- 24042163
TI  - The effects of an inhibitor of diglyceride lipase on collagen-induced platelet
      activation.
AB  - Human platelet activation by collagen occurs in a dose-dependent manner. High
      concentrations of collagen bind to a pair of receptors, the alpha2beta1 integrin
      and glycoprotein (GP)VI/Fc-receptor gamma-chain (FcRgamma), which stimulate a
      cascade of events including Syk, LAT, Btk, Gads, and phospholipase Cgamma2,
      leading to calcium release and protein kinase C (PKC) activation. Calcium and PKC
      are responsible for a range of platelet responses including exocytosis and
      aggregation, as well as the cytosolic phospholipase A2 (cPLA2)-mediated release
      of arachidonic acid, which is converted to thromboxane (Tx)A2. In contrast, low
      concentrations of collagen are acutely aspirin-sensitive, and calcium release and
      aggregation are TxA2-dependent. Under these conditions, cPLA2 is not involved and
      it has been suggested that phospholipase C generates 1,2-diacylglycerol (DG) from
      which arachidonic acid is liberated by diglyceride lipase (DGL). Here a novel DGL
      blocker (OMDM-188) inhibited collagen-, but not arachidonic acid-induced
      aggregation and TxA2 synthesis. Furthermore, OMDM-188 inhibited collagen-induced
      arachidonic acid release. Finally OMDM-188 inhibited collagen-induced p38(MAPK)
      phosphorylation, but not extracellular signal-regulated kinase (ERK)
      phosphorylation, with no effect on the phosphorylation of either enzyme in
      response to arachidonic acid. Taken together, these data suggest a role for a
      pathway involving phospholipase C liberating DG from membrane phospholipids in
      response to minimally activating concentrations of collagen. The DG serves as a
      substrate for DGL, potentially under the regulations of p38(MAPK), to release
      arachidonic acid, which is subsequently converted to TxA2, which mediates the
      final platelet response.

PMID- 24042162
TI  - cGMP-selective phosphodiesterase inhibitors stimulate mitochondrial biogenesis
      and promote recovery from acute kidney injury.
AB  - Recent studies demonstrate that mitochondrial dysfunction is a mediator of acute
      kidney injury (AKI). Consequently, restoration of mitochondrial function after
      AKI may be key to the recovery of renal function. Mitochondrial function can be
      restored through the generation of new, functional mitochondria in a process
      called mitochondrial biogenesis (MB). Despite its potential therapeutic
      significance, very few pharmacological agents have been identified to induce MB.
      To examine the efficacy of phosphodiesterase (PDE) inhibitors (PDE3: cAMP and
      cGMP activity; and PDE4: cAMP activity) in stimulating MB, primary cultures of
      renal proximal tubular cells (RPTCs) were treated with a panel of inhibitors for
      24 hours. PDE3, but not PDE4, inhibitors increased the FCCP-uncoupled oxygen
      consumption rate (OCR), a marker of MB. Exposure of RPTCs to the PDE3 inhibitors,
      cilostamide and trequinsin, for 24 hours increased peroxisome proliferator
      activated receptor gamma coactivator-1alpha, and multiple mitochondrial electron
      transport chain genes. Cilostamide and trequinsin also increased mRNA expression
      of mitochondrial genes and mitochondrial DNA copy number in mice renal cortex.
      Consistent with these experiments, 8-Br-cGMP increased FCCP-uncoupled OCR and
      mitochondrial gene expression, whereas 8-Br-cAMP had no effect. The cGMP-specific
      PDE5 inhibitor sildenafil also induced MB in RPTCs and in vivo in mouse renal
      cortex. Treatment of mice with sildenafil after folic acid-induced AKI promoted
      restoration of MB and renal recovery. These data provide strong evidence that
      specific PDE inhibitors that increase cGMP are inducers of MB in vitro and in
      vivo, and suggest their potential efficacy in AKI and other diseases
      characterized by mitochondrial dysfunction and suppressed MB. 

PMID- 24042164
TI  - How ligands improve the hydrothermal stability and affect the adsorption in the
      IRMOF family.
AB  - Metal-Organic Frameworks are considered to be the next generation of sorbents
      both because of their synthetic versatility and high selectivity potential. In
      the first generation (IRMOF), the main drawback for commercial implementation is
      the lack of hydrothermal stability. Even if several studies have been conducted
      to elucidate the reasons behind their structural weakness in humid environments,
      how apparently small changes in the stoichiometry of the building units affect
      the stability of the lattice is still poorly understood. Using density functional
      theory and ab initio molecular dynamics we investigated the reason behind the
      different behaviour of several substituted IRMOF-1 structures. We show that
      hydrophilic variations in the organic linkers work as new basins of attraction
      for the incoming water molecules, thus depleting the water content at the metal
      center. To confirm this, we performed Monte Carlo simulations to provide insights
      into the adsorption energies and check the effectiveness of the adsorption sites
      in the substituted structures for a variety of polar and non-polar molecules. The
      results show that linker modification affects molecular adsorption and can
      improve the overall stability of the lattice redirecting water to the new sites
      in the case of hydrophilic units. Three key parameters have been singled out to
      rationalize this behaviour, and used to predict the favoured adsorption sites in
      the case of gas mixtures. 

PMID- 24042165
TI  - 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ
      damage in adults with hypertension.
AB  - BACKGROUND: The mechanism that underlies the association between low 25
      hydroxyvitamin D [25(OH)D] and hypertension is not well understood; it seems to
      involve regulation of the renin-angiotensin-aldosterone system and the impact on
      endothelial function, cardiac remodeling, and subclinical organ damage. Vitamin D
      supplementation presents an ambiguous effect on endothelial function and arterial
      stiffness. We assess serum 25(OH)D3, biomarkers of endothelial dysfunction
      (soluble intercellular adhesion molecule [sICAM], C-reactive protein [CRP],
      homocysteine [Hcy]) and subclinical organ damage in adults with newly diagnosed
      untreated hypertension. METHODS: Patients were classified based on ambulatory
      blood pressure monitoring: 98 had hypertension, whereas in 60 persons BP was
      normal. Laboratory assays including serum 25(OH)D3, hsCRP, Hcy, sICAM, glucose,
      insulin, lipids, echocardiography, pulse wave velocity (PWV), intima-media
      thickness (IMT), and left-ventricular mass (LVM) measurements were performed.
      RESULTS: 25(OH)D3 was significantly lower in hypertensive patients. The logistic
      regression analysis indicated that 25(OH)D3 reduced the probability of
      hypertension occurrence after adjusting for body mass index (BMI). 25(OH)D3 in
      those with hypertension correlated significantly with systolic BP (SBP; r = 
      0.39), PWV, IMT (r = -0.33), and diastolic BP (r = -0.26). Multiple regression
      analysis in patients with hypertension revealed that 25(OH)D3 and sICAM accounted
      for up to 27% of SBP variation after adjusting for age, BMI, and smoking.
      25(OH)D3 and either PWV or IMT accounted for 23% of SBP variation. The impact of
      25(OH)D3 was 10%. CONCLUSION: The impact of 25(OH)D3 on SBP variation, mediated
      by its effect on endothelial dysfunction and subclinical organ damage, is modest
      but significant.

PMID- 24042166
TI  - Delayed heart rate recovery is strongly associated with early and late-stage
      prehypertension during exercise stress testing.
AB  - BACKGROUND: Heart rate recovery (HRR) has been shown to predict cardiovascular
      disease mortality. HRR is delayed in hypertension, but its association with
      prehypertension (PHT) has not been well studied. METHODS: The study population
      consisted of 683 asymptomatic individuals (90% men, aged 47+/-7.9 years). HRR was
      defined as peak heart rate minus heart rate after a 2-minute rest. PHT was
      categorized into stage I (systolic blood pressure (SBP) 120-129mm Hg or diastolic
      BP (DBP) 80-84mm Hg) or stage II (SBP 130-139mm Hg or DBP 85-89mm Hg). Logistic
      regression was used to generate odds ratios (ORs) for the relationship between
      HRR and PHT. RESULTS: The mean HRR was lower in the PHT groups than in those who
      were normotensive (60 bpm and 58 bpm in stages I and II PHT vs. 65 bpm in normal
      BP; P <0.01). Persons with PHT were more likely to be in the lowest quartile of
      HRR compared with those with normal BP (adjusted OR, 3.80 and 95% confidence
      interval [CI], 1.06, 13.56 for stage II PHT and adjusted OR, 3.01 and 95% CI
      1.05, 8.66 for stage I PHT). In a fully adjusted model, HRR was still
      significantly associated with both stages of PHT. CONCLUSION: Among asymptomatic
      patients undergoing stress testing, delayed HRR was independently associated with
      early and late stages of PHT. Further studies are needed to determine the
      usefulness of measuring HRR in the prevention and management of hypertension.

PMID- 24042168
TI  - Narrowing down the common deleted region of 5q to 6.0 Mb in blastic plasmacytoid
      dendritic cell neoplasms.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive
      hematologic malignancy. Simple and complex recurrent cytogenetic abnormalities
      have been reported, which demonstrate predominantly genomic losses, of which
      deletions of 5q are the most frequent aberrations in BPDCN with or without
      cutaneous manifestation; however, the gene responsible for the disease remains
      unknown. Using microarray-based molecular characterization, a recent study on
      several cases of BPDCN with the 5q deletion identified a large, common deleted
      region (CDR) of 29 Mb that contains several possible candidate genes. We report
      on a 67-year-old female patient who presented with leukemic BPDCN without skin
      involvement and had a deletion of 5q and a t(6;8)(p21;q24). By oligo-array
      comparative genome hybridization (a-CGH) method, the genomic coordinations of the
      5q deletion demonstrated unique breakpoints reported for the first time. Through
      mapping with those published cases using the same a-CGH method, the CDR was
      reduced from 29 Mb to 6 Mb, which excluded the previous candidate genes and
      highlighted an excellent biological gene: the HINT1 gene. Moreover, a molecular
      cytogenetic characterization of the translocation t(6;8) was performed in search
      for a novel gene fusion that could be associated with tumor progression. 

PMID- 24042167
TI  - How microRNAs influence both hereditary and inflammatory-mediated colon cancers.
AB  - MicroRNAs have emerged as important post-translational regulators of gene
      expression and are involved in several physiological and pathological states
      including the pathogenesis of human colon cancers. In regards to tumor
      development, microRNAs can act as oncogenes or tumor suppressors. Two hereditary
      predispositions (i.e., Lynch syndrome and familial adenomatous polyposis)
      contribute to the development of colon cancer. In addition, individuals who
      suffer from inflammatory bowel diseases such as Crohn's disease or ulcerative
      colitis have a higher risk of developing colon cancer. Here, we discuss the
      occurrence of the deregulated expression of microRNAs in colon cancer that arise
      as a result of hereditary predisposition and inflammatory bowel disease. 

PMID- 24042169
TI  - Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells
      involves differential mRNA expression of cellular genes including potential tumor
      suppressor genes on chromosome 11q13.
AB  - The fusion between human tumorigenic cells and normal human diploid fibroblasts
      results in non-tumorigenic hybrid cells, suggesting a dominant role for tumor
      suppressor genes in the generated hybrid cells. After long-term cultivation in
      vitro, tumorigenic segregants may arise. The loss of tumor suppressor genes on
      chromosome 11q13 has been postulated to be involved in the induction of the
      tumorigenic phenotype of human papillomavirus (HPV)18-positive cervical carcinoma
      cells and their derived tumorigenic hybrid cells after subcutaneous injection in
      immunocompromised mice. The aim of this study was the identification of novel
      cellular genes that may contribute to the suppression of the tumorigenic
      phenotype of non-tumorigenic hybrid cells in vivo. We used cDNA microarray
      technology to identify differentially expressed cellular genes in tumorigenic
      HPV18-positive hybrid and parental HeLa cells compared to non-tumorigenic HPV18
      positive hybrid cells. We detected several as yet unknown cellular genes that
      play a role in cell differentiation, cell cycle progression, cell-cell
      communication, metastasis formation, angiogenesis, antigen presentation, and
      immune response. Apart from the known differentially expressed genes on 11q13
      (e.g., phosphofurin acidic cluster sorting protein 1 (PACS1) and FOS ligand 1
      (FOSL1 or Fra-1)), we detected novel differentially expressed cellular genes
      located within the tumor suppressor gene region (e.g., EGF-containing fibulin
      like extracellular matrix protein 2 (EFEMP2) and leucine rich repeat containing
      32 (LRRC32) (also known as glycoprotein-A repetitions predominant (GARP)) that
      may have potential tumor suppressor functions in this model system of non
      tumorigenic and tumorigenic HeLa x fibroblast hybrid cells.

PMID- 24042170
TI  - Primary spontaneous cerebrospinal fluid leaks and idiopathic intracranial
      hypertension.
AB  - INTRODUCTION: Idiopathic intracranial hypertension (IIH) is increasingly
      recognized as a cause of spontaneous cerebrospinal fluid (CSF) leak in the
      otolarnygological and neurosurgical literature. The diagnosis of IIH in patients
      with spontaneous CSF leaks typically is made a few weeks after surgical repair of
      the leak when symptoms and signs of elevated intracranial pressure (ICP) appear.
      METHODS: Case reports and literature review. Two young obese women developed
      spontaneous CSF rhinorrhea related to an empty sella in one and a cribriform
      plate encephalocele in the other. Both patients underwent surgical repair of the
      CSF leak. A few weeks later, they developed chronic headaches and bilateral
      papilledema. Lumbar punctures showed elevated CSF opening pressures with normal
      CSF contents, with temporary improvement of headaches. A man with a 3-year
      history of untreated IIH developed spontaneous CSF rhinorrhea. He experienced
      improvement of his headaches and papilledema after a CSF shunting procedure, and
      the rhinorrhea resolved after endoscopic repair of the leak. RESULTS: These cases
      and the literature review confirm a definite association between IIH and
      spontaneous CSF leak based on: 1) similar demographics; 2) increased ICP in some
      patients with spontaneous CSF leak after leak repair; 3) higher rate of leak
      recurrence in patients with raised ICP; 4) patients with intracranial
      hypertension secondary to tumors may develop CSF leak, confirming that raised ICP
      from other causes than IIH can cause CSF leak. CONCLUSIONS: CSF leak occasionally
      may keep IIH patients symptom-free; however, classic symptoms and signs of
      intracranial hypertension may develop after a CSF leak is repaired, exposing
      these patients to a high risk of recurrence of the leak unless an ICP-lowering
      intervention is performed.

PMID- 24042171
TI  - The French version of the Reiss Screen for Maladaptive Behavior: factor
      structure, point prevalence and associated factors.
AB  - The main aims of the present study were to examine the factor structure and the
      internal consistency of the factors in the French version of the Reiss Screen of
      Maladaptive Behavior in a French-speaking European sample. The prevalence of
      psychopathology and the influence of associated factors were also examined. The
      Reiss Screen was administered to 467 adults (age range: 18-73) with intellectual
      disability living in the French-speaking regions of Switzerland and Belgium. A
      confirmatory factor analysis was performed to replicate the original factor
      structure. Internal consistency was examined by using Cronbach's alpha. Analyses
      of variance were computed to study the influence of gender, age and Down syndrome
      etiology. The original factor structure of the Reiss Screen was replicated. The
      overall rate of psychopathology in the sample was 37%. No linear relationship
      between age and psychopathology was found. However, adults aged less than 26
      years had lower scores than older adults on several psychopathological domains.
      Males had higher scores than females on the Autism and the Avoidant Disorder
      subscales. Participants with Down syndrome had lower scores on all domains, with
      the exception of the Autism subscale. The results of this study suggest that the
      French version of the Reiss Screen can be a useful tool to detect psychopathology
      in adults with intellectual disability. 

PMID- 24042172
TI  - Asthma patients' inability to use a pressurised metered-dose inhaler (pMDI)
      correctly correlates with poor asthma control as defined by the global initiative
      for asthma (GINA) strategy: a retrospective analysis.
AB  - BACKGROUND: In practice it is logical that inhalers are prescribed only after
      patients have received training and demonstrated their ability to use the device.
      However, many patients are unable to use their pressurised metered-dose inhaler
      devices (pMDIs) correctly. We assessed the relationship between asthma control
      and patients' ability to use their prescribed pMDIs. METHODS: Evaluation of 3,981
      (46% male) primary care asthma patient reviews, which included inhaler technique
      and asthma control, by specialist nurses in primary care in 2009. The paper
      focuses on people currently prescribed pMDI devices. RESULTS: Accurate data on
      reliever and preventer inhaler prescriptions were available for 3,686 and 2,887
      patients, respectively. In patients prescribed reliever inhalers, 2,375 (64%) and
      525 (14%) were on pMDI alone or pMDI plus spacer, respectively. For those
      prescribed preventers, 1,976 (68%) and 171 (6%) were using a pMDI without and
      with a spacer, respectively. Asthma was controlled in 50% of patients reviewed.
      The majority of patients (60% of 3,686) were using reliever pMDIs, 13% with
      spacers. Incorrect pMDI use was associated with poor asthma control (p<0.0001)
      and more short burst systemic steroid prescriptions in the last year (p=0.038).
      Of patients using beclometasone (the most frequently prescribed preventer drug in
      our sample), significantly more of those using a breath-actuated pMDI device
      (p<0.0001) and a spacer (p<0.0001) were controlled compared with those on pMDIs
      alone. CONCLUSIONS: Patients who are able to use pMDIs correctly have better
      asthma control as defined by the GINA strategy document. Beclometasone via a
      spacer or breath-actuated device resulted in better asthma control than via a
      pMDI alone. Patients prescribed pMDIs should be carefully instructed in technique
      and have their ability to use these devices tested; those unable to use the
      device should be prescribed a spacer or an alternative device such as one that is
      breath-actuated.

PMID- 24042173
TI  - General practitioners' contribution to the management of community-acquired
      pneumonia in the Netherlands: a retrospective analysis of primary care, hospital,
      and national mortality databases with individual data linkage.
AB  - BACKGROUND: Community-acquired pneumonia (CAP) is an important cause of hospital
      admission and death, but the extent of the problem of CAP at the primary
      healthcare level is largely unknown. AIMS: To investigate the contribution of
      general practitioners (GPs) to the management of patients with CAP in the
      Netherlands. METHODS: The study population consisted of all people enlisted in a
      GP network. We obtained information on CAP episodes from GP electronic records
      (using ICPC code R81) during the years 2002-2009. CAP registrations were also
      obtained from national hospital discharge data (ICD-9 codes) and cause of death
      statistics (ICD-10 codes). The three registration systems were linked at the
      individual level. We used descriptive analyses to estimate the annual number of
      CAP episodes (i.e. defined as a CAP diagnosis within 30 days). RESULTS: From 2002
      to 2009 the mean annual size of the study population was 395,039. For this
      population, 3,700 (0.9%) CAP episodes per year were registered in at least one of
      the registration systems, 2,933 (79%) of which were in the GP system only.
      Recovery within 30 days occurred on average in 95% (2,791/2,933) of the CAP
      episodes annually registered by a GP, while 2.3% (67/2,933) of patients with a GP
      registered CAP episode were admitted to hospital within 30 days and 1% (26/2,933)
      had a fatal outcome within 30 days. CONCLUSIONS: The vast majority of CAP
      episodes registered in the Netherlands are managed successfully at the GP level
      without hospitalisation.

PMID- 24042174
TI  - Colorimetric microchip assay using our own whole blood collected by a painless
      needle for home medical care.
AB  - We have developed a colorimetric measurement chip that measures triglycerides,
      total cholesterol, and high-density lipoprotein in 6 MUL of whole blood collected
      with a painless needle. The chip can be used by patients to self-monitor certain
      health conditions at home. This chip contains a sharp 150 MUm diameter stainless
      steel (SUS) needle that collects blood painlessly. The chip consists of three
      layers of injection-molded poly(methyl methacrylate) bonded together with two
      double-sided tapes. Two commercial reagents are used, and the volume ratio of
      plasma to reagent is doubled from the reagent specification to reduce the optical
      absorption length (and chip mass) by half. Centrifugal force separates the plasma
      from the blood, and then weighs out and mixes the plasma and reagents. A zigzag
      channel allows mixing of the plasma with the reagents mainly by vortex motion due
      to the centrifugal force generated at the corners of the channel. The measured
      values correlated well with conventionally tested values. 

PMID- 24042175
TI  - Oxytocin cells in the supraoptic nucleus receive excitatory synaptic inputs from
      the contralateral supraoptic and paraventricular nuclei in the lactating rat.
AB  - The present experiments were undertaken to examine whether oxytocin cells in the
      supraoptic nucleus receive synaptic inputs from the contralateral supraoptic
      nucleus or paraventricular nucleus. Using urethane-anesthetized lactating rats,
      extracellular action potentials were recorded from single oxytocin or vasopressin
      cells in the supraoptic nucleus. Electrical stimulation was applied to the
      contralateral supraoptic nucleus or paraventricular nucleus, and responses of
      oxytocin or vasopressin cells were analyzed by peri-stimulus time histogram or by
      change in firing rate of oxytocin or vasopressin cells. Electrical stimulation of
      the contralateral supraoptic nucleus or paraventricular nucleus did not cause
      antidromic excitation in oxytocin or vasopressin cells but caused orthodromic
      responses. Although analysis by peri-stimulus time histogram showed that
      electrical stimulation of the contralateral supraoptic nucleus or paraventricular
      nucleus caused orthodromic excitation in both oxytocin and vasopressin cells, the
      proportion of excited oxytocin cells was greater than that of vasopressin cells.
      Train stimulation applied to the contralateral supraoptic nucleus or
      paraventricular nucleus at 10 Hz increased firing rates of oxytocin cells and
      decreased those of vasopressin cells. The results of the present experiments
      suggest that oxytocin cells in the supraoptic nucleus receive mainly excitatory
      synaptic inputs from the contralateral supraoptic nucleus and paraventricular
      nucleus. Receipt these synaptic inputs to oxytocin cells may contribute to the
      synchronized activation of oxytocin cells during the milk ejection reflex. 

PMID- 24042177
TI  - Highly durable colour/emission switching of fluorescein in a thin film device
      using "electro-acid/base" as in situ stimuli.
AB  - A radical ion from electroreduced p-benzoquinone (BQ) was introduced as a new
      source of convenient in situ base for colour/emission switching of fluorescein in
      thin film devices. The devices show excellent switchability and reversibility
      with no degradation during our extended switching test of 1500 cycles. 

PMID- 24042176
TI  - Association between tissue characteristics evaluated with optical coherence
      tomography and mid-term results after paclitaxel-coated balloon dilatation for in
      stent restenosis lesions: a comparison with plain old balloon angioplasty.
AB  - AIMS: Morphological assessment of neointimal tissue using optical coherence
      tomography (OCT) is important for clarifying the pathophysiology of in-stent
      restenosis (ISR) lesions. The aim of this study was to determine the impact of
      OCT findings on recurrence of ISR after paclitaxel-coated balloon (PCB)
      dilatation compared with plain old balloon angioplasty (POBA). METHODS AND
      RESULTS: Between July 2008 and May 2012, we performed percutaneous coronary
      intervention for 214 ISR lesions using POBA + PCB (146 lesions, PCB group) or
      POBA only (68 lesions, POBA group). Morphological assessment of neointimal tissue
      using OCT, including assessment of restenotic tissue structure and restenotic
      tissue backscatter, was performed. We examined the association between lesion
      morphologies and mid-term (6-8 months) results including ISR and target lesion
      revascularization (TLR) rates. Both ISR and TLR rates of lesions with a
      homogeneous structure were significantly lower in the PCB group than those in the
      POBA group (ISR: 20.0 vs. 55.6%, P = 0.002, TLR: 12.7 vs. 37.0%, P = 0.019), but
      there was no difference between the two groups in ISR and TLR rates of lesions
      with a heterogeneous or layered structure. Both ISR and TLR rates of lesions with
      high backscatter were significantly lower in the PCB group than those in the POBA
      group (ISR: 19.8 vs. 52.5%, P < 0.001, TLR: 13.6 vs. 42.5%, P = 0.001), but there
      was no difference between the two groups in ISR and TLR rates of lesions with low
      backscatter. CONCLUSION: Morphological assessment of ISR tissue using OCT might
      be useful for identifying ISR lesions favourable for PCB dilatation.

PMID- 24042178
TI  - Neuroprotection in the NICU.

PMID- 24042179
TI  - A model of neurodevelopmental risk and protection for preterm infants.
AB  - The purpose of this article is to introduce a model of neurodevelopmental risk
      and protection that may explain some of the relationships among biobehavioral
      risks, environmental risks, and caregiving behaviors that potentially contribute
      to neurobehavioral and cognitive outcomes. Infants born before 30 weeks of
      gestation have the poorest developmental prognosis of all infants. These infants
      have lengthy hospitalization periods in the neonatal intensive care unit (NICU,)
      an environment that is not always supportive of brain development and long-term
      developmental needs. The model supports the premise that interventions focused on
      neuroprotection during the neonatal period have the potential to positively
      affect long-term developmental outcomes for vulnerable very preterm infants.
      Finding ways to better understand the complex relationships among NICU-based
      interventions and long-term outcomes are important to guiding caregiving
      practices in the NICU. 

PMID- 24042180
TI  - Relationships between environmental stressors and stress biobehavioral responses
      of preterm infants in NICU.
AB  - Although research has demonstrated that the neonatal intensive care unit (NICU)
      is a stressful environment for preterm and high-risk infants, little research
      validates the suspected relationships between infant biobehavioral responses and
      environmental stress in the NICU. This exploratory study examined the
      relationship between environmental stress and biobehavioral responses of preterm
      infants. The study used a repeated-measures research design to examine research
      variables in one group of preterm infants. Measurements of research variables
      were recorded every 2 minutes during two 60-minute observation periods for each
      research day (1 hour in the morning and 1 hour in the afternoon) and conducted
      over 2 days. A convenience sample of 37 preterm infants was recruited from 2
      medical centers in Taiwan. A total of 4164 observations were made and recorded
      during the study. There was a statistically significant (P < .05) relationship
      between environmental stressors and changes in physiological signals. There were
      also statistically significant (P < .05) relationships between environmental
      stress and some specific stress behaviors. This research is applicable to
      neonatal clinical practice because it demonstrates the importance of recognizing
      the preterm infant's biological stress responses to environmental stressors,
      allowing for early interventions to reduce the possibility of more serious
      physiological or pathological changes in the status of the preterm infant. 

PMID- 24042181
TI  - Understanding neurodevelopmental outcomes of prematurity: education priorities
      for NICU parents.
AB  - NICU nurses have an important role to play in many aspects of parent education.
      This article stresses the need for an increased focus on teaching parents about
      the central role that self-regulation will play in their infant's neurobehavioral
      development not only during the early infancy period but throughout all of
      childhood and adolescence. Suggestions are made about how to conceptualize the
      relation between cognition and emotions in humans and how to help parents
      understand that continued vigilance concerning potential problems in attention
      and self-regulation will be necessary. 

PMID- 24042183
TI  - Unidirectional suppression of hydrogen oxidation on oxidized platinum clusters.
AB  - Solar-driven water splitting to produce hydrogen may be an ideal solution for
      global energy and environment issues. Among the various photocatalytic systems,
      platinum has been widely used to co-catalyse the reduction of protons in water
      for hydrogen evolution. However, the undesirable hydrogen oxidation reaction can
      also be readily catalysed by metallic platinum, which limits the solar energy
      conversion efficiency in artificial photosynthesis. Here we report that the
      unidirectional suppression of hydrogen oxidation in photocatalytic water
      splitting can be fulfilled by controlling the valence state of platinum; this
      platinum-based cocatalyst in a higher oxidation state can act as an efficient
      hydrogen evolution site while suppressing the undesirable hydrogen back
      oxidation. The findings in this work may pave the way for developing other high
      efficientcy platinum-based catalysts for photocatalysis, photoelectrochemistry,
      fuel cells and water-gas shift reactions. 

PMID- 24042185
TI  - Pb2TiOF(SeO3)2Cl and Pb2NbO2(SeO3)2Cl: small changes in structure induced a very
      large SHG enhancement.
AB  - The replacement of NbO6 octahedra in Pb2NbO2(SeO3)2Cl by the TiO5F octahedra in
      Pb2TiOF(SeO3)2Cl induced a very large SHG enhancement from 2.3 * to 9.6 * KDP
      (KH2PO4), and both materials are type-I phase matchable. Theoretical calculations
      based on DFT methods indicate that the inclusion of F(-) anions in the d(0)-TM
      octahedral coordination unit has a great impact on the band structure and the SHG
      enhancement of the material. 

PMID- 24042186
TI  - Trends in extreme binge drinking among US high school seniors.

PMID- 24042187
TI  - To what extent does not wearing shoes affect the local dynamic stability of
      walking?: effect size and intrasession repeatability.
AB  - Local dynamic stability (stability) quantifies how a system responds to small
      perturbations. Several experimental and clinical findings have highlighted the
      association between gait stability and fall risk. Walking without shoes is known
      to slightly modify gait parameters. Barefoot walking may cause unusual sensory
      feedback to individuals accustomed to shod walking, and this may affect
      stability. The objective was therefore to compare the stability of shod and
      barefoot walking in healthy individuals and to analyze the intrasession
      repeatability. Forty participants traversed a 70 m indoor corridor wearing normal
      shoes in one trial and walking barefoot in a second trial. Trunk accelerations
      were recorded with a 3D-accelerometer attached to the lower back. The stability
      was computed using the finite-time maximal Lyapunov exponent method. Absolute
      agreement between the forward and backward paths was estimated with the
      intraclass correlation coefficient (ICC). Barefoot walking did not significantly
      modify the stability as compared with shod walking (average standardized effect
      size: +0.11). The intrasession repeatability was high (ICC: 0.73-0.81) and
      slightly higher in barefoot walking condition (ICC: 0.81-0.87). Therefore, it
      seems that barefoot walking can be used to evaluate stability without introducing
      a bias as compared with shod walking, and with a sufficient reliability. 

PMID- 24042188
TI  - Hypoxia enhances chondrogenesis and prevents terminal differentiation through
      PI3K/Akt/FoxO dependent anti-apoptotic effect.
AB  - Hypoxia, a common environmental condition, influences cell signals and functions.
      Here, we compared the effects of hypoxia (1% oxygen) and normoxia (air) on
      chondrogenic differentiation of human mesenchymal stem cells (MSCs). For in vitro
      chondrogenic differentiation, MSCs were concentrated to form pellets and
      subjected to conditions appropriate for chondrogenic differentiation under
      normoxia and hypoxia, followed by the analysis for the expression of genes and
      proteins of chondrogenesis and endochondral ossification. MSCs induced for
      differentiation under hypoxia increased in chondrogenesis, but decreased in
      endochondral ossification compared to those under normoxia. MSCs induced for
      differentiation were more resistant to apoptosis under hypoxia compared to those
      under normoxia. The hypoxia-dependent protection of MSCs from chondrogenesis
      induced apoptosis correlated with an increase in the activation of the
      phosphatidylinositol 3-kinase (PI3K)/Akt/FoxO pathway. These results suggest that
      the PI3K/Akt/FoxO survival pathway activated by hypoxia in MSCs enhances
      chondrogenesis and plays an important role in preventing endochondral
      ossification. 

PMID- 24042189
TI  - Cold snare polypectomy vs. Cold forceps polypectomy using double-biopsy technique
      for removal of diminutive colorectal polyps: a prospective randomized study.
AB  - OBJECTIVES: There are few data on cold snare polypectomy (CSP) in direct
      comparison with cold forceps polypectomy (CFP) for colonoscopic resection of
      diminutive colorectal polyps (DCPs; <=5 mm). The primary aim of this study was to
      compare the histologic polyp eradication rate of CSP with that of CFP using
      double-biopsy technique. METHODS: This was a randomized controlled trial at a
      single academic hospital. Of the 165 patients invited, 54 consecutive patients
      having 117 eligible polyps were enrolled in this study. To evaluate histologic
      eradication of polyps, two or more additional biopsies were taken from the base
      and edges of the polypectomy site. RESULTS: The mean size of polyps was 3.66 mm
      (+/-1.13). Most polyps evaluated were tubular adenomas (69.9%). The rate of
      histologic eradication was significantly higher in the CSP group than in the CFP
      group (93.2% vs. 75.9%, P=0.009). The time taken for polypectomy was
      significantly shorter in the CSP group (14.29 vs. 22.03 s, P<0.001). Failure of
      tissue retrieval was noted in 6.8% of polyps resected by CSP. Multivariate
      analysis revealed that the method of polypectomy (CFP) and the polyp size (>=4
      mm) were independent predictors associated with incomplete histologic eradication
      (odds ratio (OR) 4.750 (95% confidence interval (CI): 1.459-15.466), OR 4.375
      (95% CI: 1.345-14.235); all P<0.05, respectively). CONCLUSIONS: CSP is superior
      to CFP for the endoscopic removal of DCPs with regard to completeness of
      polypectomy. CSP technique should be considered the primary method for endoscopic
      treatment of polyps in the 4-5-mm size range (ClinicalTrials.gov number:
      NCT01646242).

PMID- 24042190
TI  - Covered self-expandable metal stents with an anti-migration system improve
      patency duration without increased complications compared with uncovered stents
      for distal biliary obstruction caused by pancreatic carcinoma: a randomized
      multicenter trial.
AB  - OBJECTIVES: The requirements of biliary stents used in the palliation of
      malignant biliary obstruction are a long duration of patency and minimal adverse
      effects. Covered self-expandable metal stents (SEMSs) have been shown to prevent
      tumor ingrowth, which is the most frequent complication of uncovered SEMSs.
      However, because they are prone to migration, the superiority of covered SEMS has
      yet to be convincingly demonstrated. The aim of this study was to evaluate the
      superiority of covered over uncovered SEMSs in the palliation of distal biliary
      obstruction due to unresectable pancreatic carcinoma, using both stent types with
      relatively low axial force and uncovered flared ends to prevent their migration.
      METHODS: From April 2009 to December 2010, 120 patients who were admitted to 22
      tertiary-care centers because of distal biliary obstruction from unresectable
      pancreatic carcinomas were enrolled in this prospective randomized multicenter
      study. Patients were randomly assigned to receive a covered or uncovered SEMS
      deployed at the site of the biliary stricture during endoscopic retrograde
      cholangiopancreatography. Stent patency time, patient survival time, patient
      survival time without stent dysfunction (time to stent dysfunction or patient
      death), cause of stent dysfunction (ingrowth, overgrowth, migration, or sludge
      formation), and serious adverse events were compared between covered and
      uncovered SEMS groups. RESULTS: Patient survival time in the two groups did not
      significantly differ (median: 285 and 223 days, respectively; P=0.68). Patient
      survival time without stent dysfunction was significantly longer in the covered
      than in the uncovered SEMS group (median: 187 vs. 132 days; P=0.043). Stent
      patency was also significantly longer in the covered than in the uncovered SEMS
      group (mean+/-s.d.: 219.3+/-159.1 vs. 166.9+/-124.9 days; P=0.047).
      Reintervention for stent dysfunction was performed in 14 of 60 patients with
      covered SEMSs (23%) and in 22 of 60 patients with uncovered SEMSs (37%; P=0.08).
      Stent dysfunction was caused by tumor ingrowth, tumor overgrowth, and sludge
      formation in 0 (0%), 3 (5%), and 11 (18%) patients in the covered SEMSs group,
      and in 15 (25%), 2 (3%), and 6 (10%) patients in the uncovered SEMSs group,
      respectively. Stent migration was not observed in either group. Rates of tumor
      overgrowth and sludge formation did not significantly differ between the two
      groups, whereas the rate of tumor ingrowth was significantly lower in the covered
      than in the uncovered SEMS group (P<0.01). Acute pancreatitis occurred in only
      one patient in the covered SEMS group. Acute cholecystitis occurred in one
      patient in the covered SEMS group and in two patients in the uncovered SEMS
      group. There was no significant difference between the two groups in the
      incidence of serious adverse events. CONCLUSIONS: By preventing tumor ingrowth
      and migration, covered SEMSs with an anti-migration system had a longer duration
      of patency than uncovered SEMSs, which recommends their use in the palliative
      treatment of patients with biliary obstruction due to pancreatic carcinomas.

PMID- 24042191
TI  - Survival in stage II/III colorectal cancer is independently predicted by
      chromosomal and microsatellite instability, but not by specific driver mutations.
AB  - OBJECTIVES: Microsatellite instability (MSI) is an established marker of good
      prognosis in colorectal cancer (CRC). Chromosomal instability (CIN) is strongly
      negatively associated with MSI and has been shown to be a marker of poor
      prognosis in a small number of studies. However, a substantial group of "double
      negative" (MSI-/CIN-) CRCs exists. The prognosis of these patients is unclear.
      Furthermore, MSI and CIN are each associated with specific molecular changes,
      such as mutations in KRAS and BRAF, that have been associated with prognosis. It
      is not known which of MSI, CIN, and the specific gene mutations are primary
      predictors of survival. METHODS: We evaluated the prognostic value (disease-free
      survival, DFS) of CIN, MSI, mutations in KRAS, NRAS, BRAF, PIK3CA, FBXW7, and
      TP53, and chromosome 18q loss-of-heterozygosity (LOH) in 822 patients from the
      VICTOR trial of stage II/III CRC. We followed up promising associations in an
      Australian community-based cohort (N=375). RESULTS: In the VICTOR patients, no
      specific mutation was associated with DFS, but individually MSI and CIN showed
      significant associations after adjusting for stage, age, gender, tumor location,
      and therapy. A combined analysis of the VICTOR and community-based cohorts showed
      that MSI and CIN were independent predictors of DFS (for MSI, hazard ratio
      (HR)=0.58, 95% confidence interval (CI) 0.36-0.93, and P=0.021; for CIN, HR=1.54,
      95% CI 1.14-2.08, and P=0.005), and joint CIN/MSI testing significantly improved
      the prognostic prediction of MSI alone (P=0.028). Higher levels of CIN were
      monotonically associated with progressively poorer DFS, and a semi-quantitative
      measure of CIN was a better predictor of outcome than a simple CIN+/- variable.
      All measures of CIN predicted DFS better than the recently described Watanabe LOH
      ratio. CONCLUSIONS: MSI and CIN are independent predictors of DFS for stage
      II/III CRC. Prognostic molecular tests for CRC relapse should currently use MSI
      and a quantitative measure of CIN rather than specific gene mutations.

PMID- 24042192
TI  - Infectious and malignant complications of TNF inhibitor therapy in IBD.
AB  - Tumor necrosis factor (TNF) inhibitors are being increasingly utilized in the
      management of inflammatory bowel disease (IBD). Although the benefits associated
      with TNF inhibitor therapy are undeniable, concerns have been raised about the
      associated risk of infectious and malignant complications. In this narrative
      review, we will present the evidence from studies that have evaluated the
      association of TNF inhibitors and both overall and specific infections and
      malignancy. Overall, although TNF inhibitors may increase the risk of
      tuberculosis, varicella, and other opportunistic infections, there is little
      evidence suggesting that anti-TNF agents specifically raise the overall risk of
      serious infections. Similarly, there is little evidence that TNF antagonists
      raise the risk of developing malignancy over and above the risks from concomitant
      therapies and the underlying disease process. However, the risk of nonmelanoma
      skin cancers may be increased and that is further enhanced by use of combination
      TNF inhibitor and thiopurine therapy. The risk of non-Hodgkin's lymphoma is
      statistically increased among combination therapy users. The absolute risk
      remains a very small but feared risk. It is difficult to fully quantify the risk
      of these cancers among users of TNF inhibitor therapy in the absence of
      concurrent thiopurine therapy. We recommend that clinicians remain mindful about
      the potential risks of infectious and malignant complications in their IBD
      patients who are using TNF inhibitors, but that further research is required to
      better study these risks over the long-term course of therapy. 

PMID- 24042193
TI  - Integrin alpha 6: a novel therapeutic target in esophageal squamous cell
      carcinoma.
AB  - Esophageal squamous cell carcinoma (ESCC), the most common subtype of esophageal
      cancer in East Asian countries, is a devastating disease characterized by
      distinctly high incidence and mortality rates. Our previous expression profile
      analysis showed that integrin alpha 6 (ITGA6) is highly expressed in ESCC
      tissues. To validate cell surface expression of ITGA6 as a novel target in ESCC,
      we investigated ITGA6 expression in tumor tissue samples and cell lines of ESCC
      and found that ITGA6 was upregulated in these cells. In vitro knockdown of ITGA6
      in ESCC cells resulted in inhibition of cell proliferation, invasion and colony
      formation. In addition, we demonstrated that ITGA6 associates with integrin beta
      4 (ITGB4), and that this heterodimer complex is upregulated in both ESCC tissues
      and cell lines. Moreover, our biodistribution results in an ESCC xenograft model
      indicated that ITGA6 is a possible target for antibody-related diagnostic and
      therapeutic modalities in ESCC. Thus, our findings suggest that ITGA6 plays an
      important role in tumorigenesis in ESCC and represents a potential therapeutic
      target in the treatment of ESCC. 

PMID- 24042194
TI  - Ferromagnetism in Nd-doped ZnO nanowires and the influence of oxygen vacancies:
      ab initio calculations.
AB  - Room-temperature ferromagnetism (RTFM) has been achieved in rare earth (RE)
      element doped ZnO nanostructures, while the mechanism of RTFM is still under
      debate. In this work, we investigated the electronic structure and magnetic
      properties of Nd-doped ZnO nanowires, and the influence of oxygen vacancies by
      using ab initio calculations. The impurity Nd atoms prefer to substitute the
      surface Zn sites and be ferromagnetically coupled with a moment of ~3.0 MUB per
      Nd in the doped ZnO nanowires, through a superexchange interaction mediated by
      the oxygen ions. More interestingly, the surface oxygen vacancy can greatly
      enhance the stability of the ferromagnetic state via the "local carriers" of Nd-
      and Zn-s electrons, which accounts for the room-temperature ferromagnetism in the
      Nd-doped ZnO nanowires. This mechanism and analysis can be applied to other rare
      earth element doped semiconductor nanostructures.

PMID- 24042196
TI  - Differential expression of the tumor suppressor A-kinase anchor protein 12 in
      human diffuse and pilocytic astrocytomas is regulated by promoter methylation.
AB  - The scaffold protein A-kinase anchor protein 12 (AKAP12) exerts tumor suppressor
      activity and is downregulated in several tumor entities. We characterized AKAP12
      expression and regulation in astrocytomas, including pilocytic and diffusely
      infiltrating astrocytomas. We examined 194 human gliomas and 23 normal brain
      white matter samples by immunohistochemistry or immunoblotting for AKAP12
      expression. We further performed quantitative methylation analysis of the AKAP12
      promoter by MassARRAY(r) of normal brain, World Health Organization (WHO) grade I
      to IV astrocytomas, and glioma cell lines. Our results show that AKAP12 is
      expressed in a perivascular distribution in normal CNS, strongly upregulated in
      tumor cells in pilocytic astrocytomas, and weakly expressed in diffuse
      astrocytomas of WHO grade II to IV. Methylation analyses revealed specific
      hypermethylation of AKAP12alpha promoter in WHO grade II to IV astrocytomas.
      Restoration experiments using 5-aza-2'-deoxycytidine in primary glioblastoma
      cells decreased AKAP12alpha promoter methylation and markedly increased
      AKAP12alpha mRNA levels. In summary, we demonstrate that AKAP12 is differentially
      expressed in human astrocytomas showing high expression in pilocytic but low
      expression in diffuse astrocytomas of all WHO-grades. Our results further
      indicate that epigenetic mechanisms are involved in silencing AKAP12 in diffuse
      astrocytomas; however, a tumor suppressive role of AKAP12 in distinct astrocytoma
      subtypes remains to be determined. 

PMID- 24042195
TI  - The expression of kainate receptor subunits in hippocampal astrocytes after
      experimentally induced status epilepticus.
AB  - Astrocytes have emerged as active participants of synaptic transmission and are
      increasingly implicated in neurologic disorders including epilepsy. Adult glial
      fibrillary acidic protein (GFAP)-positive hippocampal astrocytes are not known
      for ionotropic glutamate receptor expression under basal conditions. Using a
      chemoconvulsive status epilepticus (SE) model of temporal lobe epilepsy, we show
      by immunohistochemistry and colocalization analysis that reactive hippocampal
      astrocytes express kainate receptor (KAR) subunits after SE. In the CA1 region,
      GluK1, GluK2/3, GluK4, and GluK5 subunit expression was observed in GFAP-positive
      astrocytes during the seizure-free or "latent" period 1 week after SE. At 8 weeks
      after SE, a time after SE when spontaneous behavioral seizures occur, the GluK1
      and GluK5 subunits remained expressed at significant levels. Kainate receptor
      subunit expression was found in astrocytes in the hippocampus and surrounding
      cortex but not in GFAP-positive astrocytes of striatum, olfactory bulb, or
      brainstem. To examine hippocampal KAR expression more broadly, astroglial
      enriched tissue fractions were prepared from dissected hippocampi and were found
      to have greater GluK4 expression after SE than controls. These results
      demonstrate that astrocytes begin to express KARs after seizure activity and
      suggest that their expression may contribute to the pathophysiology of epilepsy. 

PMID- 24042198
TI  - A derivative of the brain metabolite lanthionine ketimine improves cognition and
      diminishes pathology in the 3 * Tg-AD mouse model of Alzheimer disease.
AB  - Lanthionine ketimine ([LK] 3,4-dihydro-2H-1,4-thiazine-3,5-dicarboxylic acid) is
      the archetype for a family of naturally occurring brain sulfur amino acid
      metabolites, the physiologic function of which is unknown. Lanthionine ketimine
      and its synthetic derivatives have recently demonstrated neurotrophic,
      neuroprotective, and antineuroinflammatory properties in vitro through a proposed
      mechanism involving the microtubule-associated protein collapsin response
      mediator protein 2. Therefore, studies were undertaken to test the effects of a
      bioavailable LK ester in the 3 * Tg-AD mouse model of Alzheimer disease.
      Lanthionine ketimine ester treatment substantially diminished cognitive decline
      and brain amyloid-beta (Abeta) peptide deposition and phospho-Tau accumulation in
      3 * Tg-AD mice and also reduced the density of Iba1-positive microglia.
      Furthermore, LK ester treatment altered collapsin response mediator protein 2
      phosphorylation. These findings suggest that LK may not be a metabolic waste but
      rather a purposeful neurochemical, the synthetic derivatives of which constitute
      a new class of experimental therapeutics for Alzheimer disease and related
      entities.

PMID- 24042197
TI  - Long-term analyses of innervation and neuromuscular integrity in the Trembler-J
      mouse model of Charcot-Marie-Tooth disease.
AB  - A large fraction of hereditary demyelinating neuropathies, classified as Charcot
      Marie-Tooth disease type 1A, is associated with misexpression of peripheral
      myelin protein 22. In this study, we characterized morphologic and biochemical
      changes that occur with diseaseprogression in neuromuscular tissue of Trembler-J
      mice, a spontaneous rodent model of Charcot-Marie-Tooth disease type 1A. Using
      age-matched, 2- and 10-month-old, wild-type and Trembler-J mice, we observed
      neuromuscular deficits that progress from distal to proximal regions. The
      impairments in motor performance are underlined by degenerative events at distal
      nerve segments and structural alterations at nerve-muscle synapses. Furthermore,
      skeletal muscle of affected mice showed reduced myofiber diameter, increased
      expression of the muscle atrophy marker muscle ring-finger protein 1, and fiber
      type switching. A dietary intervention of intermittent fasting attenuated these
      progressive changes and supported distal nerve myelination and neuromuscular
      junction integrity. In addition to the well-characterized demyelination aspects
      of this model, our investigations identified distinct degenerative events in
      distal nerves and muscle of affected neuropathic mice. Therefore, therapeutic
      studies aimed at slowing or reversing the neuropathic features of these disorders
      should include the examination of muscle tissue, as well as neuromuscular contact
      sites. 

PMID- 24042199
TI  - Alpha-B-crystallin induces an immune-regulatory and antiviral microglial response
      in preactive multiple sclerosis lesions.
AB  - Microglial nodules are frequently observed in the normal-appearing white matter
      of multiple sclerosis (MS) patients. Previously, we have shown that these
      clusters, which we call "preactive MS lesions," are closely associated with
      stressed oligodendrocytes and myelin sheaths that contain markedly elevated
      levels of the small stress protein alpha-B-crystallin (HspB5). Here, we show that
      microglia in these lesions express the recently identified receptors for HspB5,
      that is, CD14, Toll-like receptor family 1 and 2 (TLR1 and TLR2), and several
      molecular markers of the microglial response to HspB5. These markers were
      identified by genome-wide transcript profiling of 12 primary human microglial
      cultures at 2 time points after exposure to HspB5. These data indicate that HspB5
      activates production by microglia of an array of chemokines, immune-regulatory
      mediators, and a striking number of antiviral genes that are generally inducible
      by type I interferons. Together, our data suggest that preactive MS lesions are
      at least in part driven by HspB5 derived from stressed oligodendrocytes and may
      reflect a local attempt to restore tissue homeostasis. 

PMID- 24042200
TI  - Blockade of interleukin 6 signaling improves the survival rate of transplanted
      bone marrow stromal cells and increases locomotor function in mice with spinal
      cord injury.
AB  - Bone marrow stromal cells (BMSCs) have the potential to improve functional
      recovery in patients with spinal cord injury (SCI); however, they are limited by
      low survival rates after transplantation in the injured tissue. Our objective was
      to clarify the effects of a temporal blockade of interleukin 6 (IL-6)/IL-6
      receptor (IL-6R) engagement using an anti-mouse IL-6R monoclonal antibody (MR16
      1) on the survival rate of BMSCs after their transplantation in a mouse model of
      contusion SCI. MR16-1 cotreatment improved the survival rate of transplanted
      BMSCs, allowing some BMSCs to differentiate into neurons and astrocytes, and
      improved locomotor function recovery compared with BMSC transplantation or MR16-1
      treatment alone. The death of transplanted BMSCs could be mainly related to
      apoptosis rather than necrosis. Transplantation of BMSC with cotreatment of MR16
      1 was associated with a decrease of some proinflammatory cytokines, an increase
      of neurotrophic factors, decreased apoptosis rates of transplanted BMSCs, and
      enhanced expression of survival factors Akt and extracellular signal-regulated
      protein kinases 1/2. We conclude that MR16-1 treatment combined with BMSC
      transplants helped rescue neuronal cells and axons after contusion SCI better
      than BMSCs alone by modulating the inflammatory/immune responses and decreasing
      apoptosis. 

PMID- 24042201
TI  - Skeletal muscle microvasculature in the diagnosis of neuromuscular disease.
AB  - Blood vessels are often overlooked in analyses of skeletal muscle biopsies.
      However, there are many vascular features in skeletal muscle biopsies that, when
      interpreted in the context of other histologic patterns and clinical history,
      provide useful information that allows muscle pathologists to narrow their
      differential diagnoses and provide more accurate guidance to treating physicians.
      Here, we provide a review of normal skeletal muscle vasculature with details of
      the ultrastructure of vessel walls. We discuss the vascular effects of factors
      common to many patients undergoing muscle biopsy, for example, diabetes mellitus,
      hypertension, and aging. We then discuss vascular findings relevant to diagnostic
      muscle biopsy evaluation, with current theories of pathogenesis and detailed
      descriptions of the important features. 

PMID- 24042203
TI  - Benzocaine-induced methaemoglobinaemia: a life-threatening complication after a
      transoesophageal echocardiogram (TEE).
AB  - Acquired methaemoglobinaemia is a potentially fatal impairment in oxygen delivery
      if not recognised early and treated appropriately. Benzocaine used as an
      anaesthetic for endoscopic procedures is an uncommon but clinically important
      precipitant of acquired methaemoglobinaemia. We present a case of an elderly
      woman who developed perioral cyanosis and desaturation 20 min after a
      transoesophageal echocardiogram. Further evaluation led to the diagnosis of
      benzocaine-induced methaemoglobinaemia and timely treatment with intravenous
      methylene blue was initiated. 

PMID- 24042204
TI  - Capsule endoscopy: a dangerous but diagnostic tool.
AB  - Current guidelines advocate the use of capsule endoscopy (CE) when gastroscopy
      and colonoscopy have failed to demonstrate the origin of occult gastrointestinal
      bleeding. CE has been used successfully in the diagnosis of a variety of
      conditions such as coeliac disease, polyposis syndromes and small bowel tumours,
      when routine investigations have failed to yield a diagnosis. In conditions where
      the diameter of the bowel lumen may be compromised, such as Crohn's disease, CE
      is contraindicated because of the risk of retention and/or small bowel
      obstruction. Here we present an unusual case where CE resulted in small bowel
      obstruction and perforation in a segment of small bowel which had become inflamed
      secondary to a carcinoid tumour. 

PMID- 24042205
TI  - Complete radiographic remission with 5-fluorouracil and leucovorin after
      sorafenib failure in hepatocellular carcinoma: is there a role for chemotherapy
      after targeted agents?
AB  - A 57-year-old Caucasian man with a history of Child's class A hepatitis C,
      cirrhosis and progressive multifocal hepatocellular carcinoma was treated with
      sorafenib but progressed after 7 months of stable disease. At progression he was
      given salvage chemotherapy consisting of 5-fluorouracil and leucovorin and went
      into complete radiographic remission after 12 cycles of treatment. He did develop
      a portal vein thrombosis but nevertheless his hepatic lesions continued to
      resolve. Throughout his therapy alpha-fetoprotein (AFP) levels decreased only
      minimally. He did not seek retreatment after 14 cycles of chemotherapy and
      presented 3 months later with relapsed disease on CT scans with markedly elevated
      AFP levels. He received one more chemotherapy cycle but was unable to tolerate
      further treatment, succumbing to his disease 3 months thereafter, and a total of
      29 months after he was deemed a sorafenib failure. 

PMID- 24042206
TI  - A stepwise approach to 'groin pain': a common symptom, an uncommon cause.
AB  - A 70-year-old man was admitted with stinging pain in his right groin radiating
      towards his inner thigh. In a few days, the pain increased in intensity, he
      experienced diminished strength in his right leg and got dependent on morphine.
      Conventional investigations did not show any pathology. A CT-scan revealed a mass
      in the obturator foramen, indicative of a possible obturator hernia or neuroma of
      the obturator nerve. However, an additional MRI showed a well-circumscribed
      cystic mass in the obturator foramen, indicative of a ganglion cyst. This cyst
      was percutaneously punctured under the CT-guidance and the viscous material was
      aspirated, after which corticosteroids were injected. After the puncture all
      symptoms of the patient had completely resolved and the patient was discharged
      from the hospital without any painkillers. 

PMID- 24042202
TI  - If the cap fits, wear it: an overview of telomeric structures over evolution.
AB  - Genome organization into linear chromosomes likely represents an important
      evolutionary innovation that has permitted the development of the sexual life
      cycle; this process has consequently advanced nuclear expansion and increased
      complexity of eukaryotic genomes. Chromosome linearity, however, poses a major
      challenge to the internal cellular machinery. The need to efficiently recognize
      and repair DNA double-strand breaks that occur as a consequence of DNA damage
      presents a constant threat to native chromosome ends known as telomeres. In this
      review, we present a comparative survey of various solutions to the end
      protection problem, maintaining an emphasis on DNA structure. This begins with
      telomeric structures derived from a subset of prokaryotes, mitochondria, and
      viruses, and will progress into the typical telomere structure exhibited by
      higher organisms containing TTAGG-like tandem sequences. We next examine non
      canonical telomeres from Drosophila melanogaster, which comprise arrays of
      retrotransposons. Finally, we discuss telomeric structures in evolution and
      possible switches between canonical and non-canonical solutions to chromosome end
      protection. 

PMID- 24042207
TI  - Hepatic heterotopia in congenital diaphragmatic anomaly.
AB  - An antenatally diagnosed case of a left congenital diaphragmatic hernia is
      reported. The diaphragmatic eventration hernia sac consisted of a sheet of
      ectopic liver tissue in continuity with a hypoplastic left lobe which formed the
      medial anterior and posterior walls of the hernia is presented. The operative
      management of this combination of defects has not previously been described in
      English literature. Embryological considerations, limitations of accurate
      preoperative diagnosis, technical challenge in the operative repair of the defect
      and need for drainage is discussed. 

PMID- 24042209
TI  - Giant penile elephantiasis after circumcision: a devastating complication.

PMID- 24042208
TI  - Hypoxic hepatitis and acute liver failure in a patient with newly onset atrial
      fibrillation and diltiazem infusion.
AB  - Hypoxic hepatitis (HH) most commonly results from haemodynamic instability and
      disruption of hepatic flow. The vast majority of cases are caused by cardiac
      failure, respiratory failure and septic shock. We report a case of HH, acute
      liver failure, acute kidney failure and progressive thrombocytopenia that
      developed following a hypotensive episode in a patient treated with intravenous
      diltiazem for a newly developed atrial fibrillation (A-fib). The pre-existing
      liver diseases, including chronic alcohol use and liver congestion secondary to
      right heart dysfunction, might have predisposed the patient to the development of
      HH. The patient was given supportive treatment and experienced full recovery of
      both liver and kidney function. To our knowledge, this is the first reported case
      of HH that occurred following ventricular rate control for acute A-fib. For
      patients with underlying liver diseases, closer blood pressure monitoring is
      warranted during diltiazem infusion. 

PMID- 24042210
TI  - Postural orthostatic tachycardia syndrome (POTS).
AB  - Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous group of
      conditions characterised by autonomic dysfunction and an exaggerated sympathetic
      response to assuming an upright position. Up till recently, it was largely under
      recognised as a clinical entity. There is now consensus about the definition of
      POTS as a greater than 30/min heart rate increase on standing from a supine
      position (greater than 40/min increase in 12-19-year-old patients) or an absolute
      heart rate of greater than 120/min within 10 min of standing from a supine
      position and in the absence of hypotension, arrhythmias, sympathomimetic drugs or
      other conditions that cause tachycardia. We present two cases of POTS, followed
      by a discussion of its pathogenesis, pathophysiology, epidemiology and
      management. 

PMID- 24042211
TI  - Retained faecolith: an avoidable complication of laparoscopic appendicectomy.
AB  - A 26-year-old woman presented to the accident and emergency department 9 days
      post laparoscopic appendicectomy for a non-perforated, but gangrenous
      appendicitis. She was found to have a retained faecolith with a pelvic abscess.
      This case demonstrates one of the common pitfalls of the laparoscopic
      appendicectomy and we discuss some technical points to avoid such complications. 

PMID- 24042212
TI  - The 3-night hospital stay and Medicare coverage for skilled nursing care.

PMID- 24042213
TI  - Sternal "retraction": a novel application of a mandibular distractor in treating
      ectopia cordis with complete cleft sternum.
AB  - Complete thoracic ectopia cordis is associated with a uniformly dismal prognosis.
      The primary challenges of this disorder are (1) returning the heart to the
      thoracic cavity, (2) stabilizing the chest wall, and (3) repairing the sternal
      defect. Previously published techniques for achieving these goals have
      demonstrated very limited success and/or significant morbidity.We present a novel
      application of a mandibular distraction device as part of staged repair of this
      historically challenging problem. This method uses immediate stabilization and
      gradual "retraction" of the sternal remnants, thereby allowing physiologic
      compensation and avoiding the cardiorespiratory embarrassment associated with
      returning the heart to the thoracic cavity. Moreover, this technique allows
      stabilization of the associated sternal cleft and chest wall without the commonly
      associated morbidity of the currently available techniques. 

PMID- 24042214
TI  - Effect of conceptus on transforming growth factor (TGF) beta1 mRNA expression and
      protein concentration in the porcine endometrium--in vivo and in vitro studies.
AB  - Transforming growth factor (TGF) beta and its receptors are expressed at the
      conceptus-maternal interface during early pregnancy in the pig. The present
      studies were conducted to examine: (1) the effect of conceptus products on
      TGFbeta1 mRNA expression and protein concentration in the porcine endometrium
      using in vivo and in vitro models, and (2) the effect of TGFbeta1 on
      proliferation of porcine trophoblast cells in vitro. During in vivo experiments,
      gilts with one surgically detached uterine horn were slaughtered on days 11 or 14
      of the estrous cycle and pregnancy. For in vitro studies, endometrial explants
      and luminal epithelial (LE) cells co-cultured with stromal (ST) cells were
      treated with conceptus-exposed medium (CEM). Moreover, porcine trophoblast cells
      were treated with TGFbeta1, and the number of viable cells was measured. On day
      11, the presence of conceptuses had no effect on TGFbeta1 mRNA expression, but
      decreased the TGFbeta1 protein concentration in the connected uterine horn
      compared with the detached uterine horn. In contrast to day 11, on day 14 after
      estrus, TGFbeta1 mRNA expression and protein content in the endometrium collected
      from the gravid uterine horn were greater when compared with the contralateral
      uterine horn. The treatment of endometrial slices with CEM resulted in greater
      TGFbeta1 mRNA expression and protein secretion. LE cells responded to CEM with an
      increased TGFbeta1 mRNA level. Moreover, TGFbeta1 stimulated the proliferation of
      day 14 trophoblast cells. In summary, porcine conceptuses may regulate TGFbeta1
      synthesis in the endometrium at the time of implantation. TGFbeta1, in turn, may
      promote conceptus development by increasing the proliferation of trophoblast
      cells. 

PMID- 24042215
TI  - Recall of observed actions modulates the end-state comfort effect just like
      recall of one's own actions.
AB  - Previous studies showed that initial comfort of a posture is traded for a better
      control at the end position, a phenomenon which has been termed the end-state
      comfort effect. When participants recall a recently performed motor plan, the end
      state comfort effect is reduced. Two experiments investigated whether observing
      the grasp of another person is sufficient for later recall. Participants moved an
      object from a home location to different target positions. Results replicated an
      end-state comfort effect, revealing an inverse relation of grasp height to target
      height for the first movement. When participants later returned the object back
      to the home position, recall of the previously self-performed action dominated,
      replicating the reduction in end-state comfort due to recall processes. Notably,
      the end-state comfort effect was also reduced in conditions in which a model
      performed the first movement and in which the participant performed only the
      second movement (Experiment 1). Model actions were also recalled in situations in
      which the observed action was incongruent with a comfortable end position of the
      participant (Experiment 2). These results suggest that observed actions of others
      can serve as templates for movement planning in social situations. 

PMID- 24042216
TI  - The serotonin 5-HT7 receptors: two decades of research.
AB  - Like most neurotransmitters, serotonin possesses a simple structure. However, the
      pharmacological consequences are more complex and diverse. Serotonin is involved
      in numerous functions in the human body including the control of appetite, sleep,
      memory and learning, temperature regulation, mood, behavior, cardiovascular
      function, muscle contraction, endocrine regulation, and depression. Low levels of
      serotonin may be associated with several disorders, namely increase in aggressive
      and angry behaviors, clinical depression, Parkinson's disease, obsessive
      compulsive disorder, eating disorders, migraine, irritable bowel syndrome,
      tinnitus, and bipolar disease. These effects are mediated via different serotonin
      (5-HT) receptors. In this review, we will focus on the last discovered member of
      this serotonin receptor family, the 5-HT7 receptor. This receptor belongs to the
      G protein-coupled receptor superfamily and was cloned two decades ago. Later,
      different splice variants were described but no major functional differences have
      been described so far. All 5-HT7 receptor variants are coupled to Galphas
      proteins and stimulate cAMP formation. Recently, several interacting proteins
      have been reported, which can influence receptor signaling and trafficking. 

PMID- 24042218
TI  - Pharmacotherapy: beta-Blocker therapy before PCI for STEMI reduces infarct size.

PMID- 24042219
TI  - Diabetes: Cardiovascular safety of 'gliptin' therapy.

PMID- 24042217
TI  - Optimal revascularization for complex coronary artery disease.
AB  - Patients with major or symptomatic coronary artery disease (CAD) commonly undergo
      revascularization--either with CABG surgery, which has been the mainstay of
      revascularization for more than half a century, or with percutaneous coronary
      intervention (PCI), which has become the more-commonly used strategy in the past
      decade. PCI has been tested in more randomized clinical trials than any other
      procedure in contemporary practice. In general, PCI is the preferred option for
      treating patients with simple coronary artery lesions and CABG surgery remains
      the standard of care for patients with complex CAD. Technical advancements in PCI
      and CABG surgery make comparisons of historical data for these strategies
      difficult. In this Review, we evaluate the evidence-based use of PCI and CABG
      surgery in treating patients with multivessel and unprotected left main stem
      disease and for specific patient groups, including those with diabetes mellitus,
      chronic heart failure, or chronic kidney disease. Finally, we highlight the
      available tools to aid decision-making, including clinical guidelines, risk
      scoring systems, and the role of the 'heart team'.

PMID- 24042220
TI  - Heart failure: CRT contraindicated in patients with short QRS duration.

PMID- 24042224
TI  - Interventional cardiology: Does preventive PCI reduce the risk of adverse events
      in patients with acute STEMI?

PMID- 24042227
TI  - Venous thromboembolism: Edoxaban: as effective and safer than warfarin in VTE.

PMID- 24042228
TI  - Anticoagulation therapy: Results of RE-ALIGN disappoint.

PMID- 24042230
TI  - Anticoagulation therapy: Otamixaban fails in NSTE-ACS.

PMID- 24042232
TI  - Aftershocks following the 9 april 2013 bushehr earthquake, iran.
AB  - On 9 April 2013 at 11:52 UTC (16:22 local time), a Mw 6.2 earthquake occurred at
      the depth of 20 Km in Dashti district in south-west Iran's Bushehr province. The
      macroseismic epicenter was located nearby the city of Shonbeh. During one month
      after the earthquake, a total of 282 aftershocks hit the epicentral region,
      mostly at the east and north sides. They ranged from 2.5 to 5.7 on the Richter
      scale. Seventy aftershocks (24.9%) were M4.0-4.9 and eight (2.8%) were M5.0-5.7.
      Aftershocks are potentially able to do additional damage. In Bushehr earthquake,
      a M5.4 aftershock on 10 April in Chahgah village caused at least four injuries
      and destruction of several buildings that had been already damaged by the main
      shock. Knowledge about the aftershock induced damages provides opportunities for
      timely risk communication with the affected people and for long term community
      education. This will hopefully increase the community awareness and minimize the
      risk of further loss of lives. 

PMID- 24042231
TI  - EBV-LMP1-targeted DNAzyme induces DNA damage and causes cell cycle arrest in LMP1
      positive nasopharyngeal carcinoma cells.
AB  - This study aimed to determine the molecular mechanisms underlying the effect of
      the LMP1-targeted DNAzyme 1 (DZ1) on cell cycle progression in nasopharyngeal
      carcinoma (NPC) cells. We showed that the active DZ1 inhibited the expression of
      latent membrane protein 1 (LMP1) and induced a G1 phase arrest. In addition, this
      cell cycle deregulation was shown to be accompanied by upregulation of the DNA
      damage marker gamma-H2AX, downregulation of the DNA damage response factor p-p53
      Ser15 and cell proliferation inhibition. To investigate what affected the cell
      cycle progression, we examined the expression of two checkpoint-related cyclins
      and cyclin-dependent kinases (CDKs). We found a decrease of cyclin D1 and cyclin
      E protein levels at 24 h from the DZ1 treatment. Moreover, we observed inhibition
      of CDK4 activity and decreased cyclin D1 expression in the complexes
      immunoprecipitated with CDK4 antibody. We also found a reduction in cdc2
      phosphorylation at Thr161 which partially stands for the cdc2 kinase activity in
      DZ1-treated CNE1-LMP1 cells, although the downregulation of LMP1 expression had
      no effect on the cyclin B1 and cdc2 expression. Further, we analyzed changes in
      cdc2 kinase activity induced by DZ1 and found that the downregulation of the LMP1
      expression resulted in a 5-fold reduction in cdc2 kinase activity in CNE1-LMP1.
      The data suggest that the downregulation of the LMP1 expression by DZ1 was able
      to induce DNA damage, which then further inhibited the cell proliferation and
      resulted in malfunction of cell cycle checkpoints that led to G1 phase arrest and
      the decrease in number of cells in G2/M phase.

PMID- 24042234
TI  - A manganese-doped polymeric framework of polyoxotitanate nanoclusters with a
      narrow band gap.
AB  - A three-dimensional coordination polymer based on a manganese-doped
      polyoxotitanate nanocluster, {Ti13Mn4O16[MeC(CH2O)3]4(OEt)12Br4}infinity, has
      been synthesized under solvothermal conditions. It is the first framework of
      doped polyoxotitanate nanoclusters reported in the literature. Compared with
      anatase, its band gap is reduced from 3.19 to 2.57 eV. 

PMID- 24042235
TI  - Investigation of the p-coronene series in the context of the 'annulene-within-an
      annulene' model by means of ipso-centric ab initio calculations of pi-electron
      currents.
AB  - The graph-theoretical Huckel-London-Pople-McWeeny (HLPM) approach to pi-electron
      ring-currents and bond-currents was recently applied to a newly defined series of
      hypothetical conjugated hydrocarbons called the p-coronenes (with p odd and p >
      3) and that investigation ostensibly indicated that the first four of these
      structures conform to the annulene-within-an-annulene model [Dickens et al.,
      Phys. Chem. Chem. Phys., 2013, 12, 8245]. However, more-refined calculations
      reported here, which are based on a more-realistic geometry and the ipso-centric
      ab initio formalism, contradict this finding and indicate that, so far, the only
      member of the p-coronene series that definitely obeys the AWA rule is its very
      first member, 5-coronene (also known as [10,5] coronene). 

PMID- 24042236
TI  - The economic impact of childhood food allergy in the United States.
AB  - IMPORTANCE: Describing the economic impact of childhood food allergy in the
      United States is important to guide public health policies. OBJECTIVE: To
      determine the economic impact of childhood food allergy in the United States and
      caregivers' willingness to pay for food allergy treatment. DESIGN, SETTING, AND
      PARTICIPANTS: A cross-sectional survey was conducted from November 28, 2011,
      through January 26, 2012. A representative sample of 1643 US caregivers of a
      child with a current food allergy were recruited for participation. MAIN OUTCOMES
      AND MEASURES: Caregivers of children with food allergies were asked to quantify
      the direct medical, out-of-pocket, lost labor productivity, and related
      opportunity costs. As an alternative valuation approach, caregivers were asked
      their willingness to pay for an effective food allergy treatment. RESULTS: The
      overall economic cost of food allergy was estimated at $24.8 (95% CI, $20.6
      $29.4) billion annually ($4184 per year per child). Direct medical costs were
      $4.3 (95% CI, $2.8-$6.3) billion annually, including clinician visits, emergency
      department visits, and hospitalizations. Costs borne by the family totaled $20.5
      billion annually, including lost labor productivity, out-of-pocket, and
      opportunity costs. Lost labor productivity costs totaled $0.77 (95% CI, $0.53
      $1.0) billion annually, accounting for caregiver time off work for medical
      visits. Out-of-pocket costs were $5.5 (95% CI, $4.7-$6.4) billion annually, with
      31% stemming from the cost of special foods. Opportunity costs totaled $14.2 (95%
      CI, $10.5-$18.4) billion annually, relating to a caregiver needing to leave or
      change jobs. Caregivers reported a willingness to pay of $20.8 billion annually
      ($3504 per year per child) for food allergy treatment. CONCLUSIONS AND RELEVANCE:
      Childhood food allergy results in significant direct medical costs for the US
      health care system and even larger costs for families with a food-allergic child.

PMID- 24042237
TI  - Toxicology and carcinogenesis studies of a nondecolorized [corrected] whole leaf
      extract of Aloe barbadensis Miller (Aloe vera) in F344/N rats and B6C3F1 mice
      (drinking water study).
AB  - BACKGROUND: Extracts from the leaves of the Aloe vera plant (Aloe barbadensis
      Miller) have long been used as herbal remedies and are also now promoted as a
      dietary supplement, in liquid tonics, powders or tablets, as a laxative and to
      prevent a variety of illnesses. We studied the effects of Aloe vera extract on
      rats and mice to identify potential toxic or cancer-related hazards. METHODS: We
      gave solutions of nondecolorized extracts of Aloe vera leaves in the drinking
      water to groups of rats and mice for 2 years. Groups of 48 rats received
      solutions containing 0.5%, 1% or 1.5% of Aloe vera extract in the drinking water,
      and groups of mice received solutions containing 1%, 2%, or 3% of Aloe vera
      extract. Similar groups of animals were given plain drinking water and served as
      the control groups. At the end of the study tissues from more than 40 sites were
      examined for every animal. RESULTS: In all groups of rats and mice receiving the
      Aloe vera extract, the rates of hyperplasia in the large intestine were markedly
      increased compared to the control animals. There were also increases in
      hyperplasia in the small intestine in rats receiving the Aloe vera extract,
      increases in hyperplasia of the stomach in male and female rats and female mice
      receiving the Aloe vera extract, and increases in hyperplasia of the mesenteric
      lymph nodes in male and female rats and male mice receiving the Aloe vera
      extract. In addition, cancers of the large intestine occurred in male and female
      rats given the Aloe vera extract, though none had been seen in the control groups
      of rats for this and other studies at this laboratory. CONCLUSIONS: We conclude
      that nondecolorized Aloe vera caused cancers of the large intestine in male and
      female rats and also caused hyperplasia of the large intestine, small intestine,
      stomach, and lymph nodes in male and female rats. Aloe vera extract also caused
      hyperplasia of the large intestine in male and female mice and hyperplasia of the
      mesenteric lymph node in male mice and hyperplasia of the stomach in female mice.

PMID- 24042238
TI  - Weight lifted and countermovement potentiation of power in concentric phase of
      unstable and traditional resistance exercise.
AB  - The study evaluates the effect of weight lifted on power in the concentric phase
      of resistance exercises on stable and unstable surfaces. A group of 19 fit men
      performed randomly on different days 3 reps of (a) barbell chest presses on the
      bench and Swiss ball, and (b) barbell squats on stable base and BOSU ball.
      Exercises were performed without and with countermovement (CM) using maximal
      effort in concentric phase. Initial weight of 20 kg was increased by 10 kg or 5
      kg (at higher loads) up to at least 85% of previously established 1RM under
      stable conditions. Results showed no significant differences in mean power in the
      concentric phase of stable and unstable CM chest presses at lower weights lifted
      (from 20 to 50 kg). However, its values were significantly higher during chest
      presses on the bench than on Swiss ball while lifting higher weights (from 60 to
      90 kg). Similarly, mean power in the concentric phase of squats was significantly
      higher on stable base than on BOSU ball at higher weights lifted (from 60 to 90
      kg). Though a set of data showed significant differences, the effect sizes<=0.7
      suggest no practically meaningful differences. It may be concluded that unstable
      base compromises the power in the concentric phase of resistance exercises,
      however, only at higher weights lifted.

PMID- 24042239
TI  - Multiplex ligation-dependent probe amplification (MLPA) for ultrasensitive
      multiplexed microRNA detection using ribonucleotide-modified DNA probes.
AB  - Using the ribonucleotide-modified DNA probes, multiple microRNAs can be
      simultaneously detected in one ligation-based PCR reaction. As low as 0.2 fM
      microRNA can be accurately detected with high specificity. 

PMID- 24042240
TI  - Integrated care.

PMID- 24042241
TI  - Future research needs for evaluating the integration of mental health and
      substance abuse treatment with primary care.
AB  - Research needs are many in the current health care environment. In this article,
      we describe a novel method developed by the Agency for Healthcare Research and
      Quality (AHRQ) Evidence-based Practice Center Program for prioritizing areas for
      future research. Using a recent- ly published systematic review as a foundation,
      investigators worked with a diverse group of 10 stakeholders to identify and
      prioritize research needs. We enumerate 13 high-priority research needs, as
      determined by stakeholders who represented researchers, funders, health care
      providers, and patients and families, and discuss considerations for specific
      study designs. Our findings suggest that future research on integrating mental
      health and primary care should focus first on a) identifying methods of
      integrating primary care into specialty mental health settings, b) identifying
      cross-cutting strategies for integration across multiple mental health diagnostic
      categories as opposed to a separate strategy for each diagnostic category, and c)
      examining the use of information technology for integrating mental and general
      medical health care. Other priorities for consideration include examining the
      economic and organizational sus- tainability of successful integration models,
      identifying dissemination methods for various settings, examining the business
      case for integration as well as methods of payment, assessing the cost
      effectiveness of integration, and identifying key components of successful
      strategies. The importance of sustainability and economic justification for
      integrated care strategies was a recurring theme in discussions with the stake-
      holders. The ability to sustain integrated care in everyday practice remains to
      be proved and will depend in part on the level of incentives and sup- port
      provided through payment system reform, as well as the ability of practices to
      provide care efficiently.

PMID- 24042242
TI  - Metabolic monitoring of patients prescribed second-generation antipsychotics.
AB  - OBJECTIVES: This study evaluated how clinicians monitored glucose, lipids, body
      mass index (BMI), and blood pressure (BP) of patients being treated with second
      generation antipsychotics (SGAs) before and after the publication of the American
      Diabetes Association (ADA) and American Psychiatric Association (APA) Consensus
      Statement concerning antipsychotic drugs and obesity and diabetes in February,
      2004. METHODS: A retrospective analysis of GE Centricity electronic health
      records for the 2001-2008 period was conducted. SGA-naive patients receiving
      monotherapy with any SGA (aripiprazole, clozapine, olanzapine, quetiapine,
      risperidone, ziprasidone) were identified. Two scenarios were examined: The "Any"
      monitoring scenario was defined as at least one instance of monitoring of a
      parameter at any time point during the observation period (from 30 days before
      beginning the SGA until 395 days after beginning the SGA); the "Full" monitoring
      scenario was defined as a situation in which the number of times a parameter was
      monitored during the observation period was equal to the yearly frequency
      recommended by ADA/APA. Pre- and post-consensus statement monitoring rates were
      computed and monitoring trends were evaluated by quarterly time intervals using
      segmented time-series design. RESULTS: The final sample consisted of 24,826
      patients, with mean age of 47.9 years, 61% of whom were female. Pre- and post-
      consensus statement monitoring compared as following: "Any" scenario: BP (92%
      [pre] vs. 94% [post]), BMI (66% vs. 77%), glucose (60% vs. 65%), lipids (36% vs.
      41%); "Full" scenario; BP (72% vs. 75%), BMI (23% vs. 27%), glucose (23% vs.
      27%), lipids (17% vs. 20%). Regression analyses found the following per quarter
      increases in the post-con- sensus statement period for the "Any" scenario:
      glucose (1.4%, p = 0.003), lipids (1.0%, p = 0.008), BP (0.6%, p = 0.006) and the
      following per quarter increases for the "Full" scenario: glucose (1.0%, p =
      0.002), lipids (1.2%, p < 0.001) and BP (1.3%, p = 0.004). CONCLUSIONS: The
      publication of the Consensus Statement alone did not make a clinically meaningful
      difference to monitoring rates.

PMID- 24042243
TI  - Early intervention and the treatment of prodrome in schizophrenia: a review of
      recent developments.
AB  - OBJECTIVE: Strategies for preventing the development of schizophrenia are in
      their infancy but are associated with much hope and potential. The relatively
      long prodrome in schizophrenia allows for indicated prevention as an effective
      intervention. "High-risk" individuals have subtle symptoms and, without
      intervention, a third would develop psychosis within 1 year, and many will have
      poor functional outcomes, even in the absence of psychosis. Research in this area
      is preliminary but encouraging. METHODS: A literature search was performed using
      databases including PubMed, PsychInfo, and Cochrane, as well as a search of
      individual journals through cross-referencing. The search used the following key
      words: schizophrenia, psychosis, psychotic disorders, first episode, early,
      prodrome, prodromal, prevention, ultra high risk, at risk, and intervention.
      RESULTS: Strategies for preventing the development of schizophrenia are divided
      into universal, selective, and indicated levels of prevention. The common
      preventive methods include treatment with antipsychotic medications and
      psychotherapy. Early intervention helps at risk individuals with symptom
      reduction and appears to delay conversion to full blown psychosis. However, the
      criteria for identifying at risk individuals have low predictive value, which
      raises concerns about unnecessary and potentially harmful interventions.
      CONCLUSION: Although a range of interventions appear to be effective in reducing
      rates of transition to psychosis, they are inadequately differentiated and
      require further study. Current data suggest that clinicians take an
      individualized approach to intervention, considering the risk-benefit ratio on a
      case-by-case basis.

PMID- 24042244
TI  - Grief, depression, and the DSM-5.
AB  - Based on a review of the best available evidence and the importance of providing
      clinicians an opportunity to ensure that patients and their families receive the
      appropriate diagnosis and the correct intervention without necessarily being
      constrained by a somewhat arbitrary 2-month period of time, the DSM-5 Task Force
      recommended eliminating the "bereavement exclusion" (BE) from the diagnosis of
      major depressive disorder. This article reviews the initial rationale for
      creating a BE in DSM-III, reasons for not carrying the BE into DSM-5, and sources
      of continued controversy. The authors argue that removing the BE does not
      "medicalize" or "pathologize" grief, "stigmatize" bereaved persons, imply that
      grief morphs into depression after 2 weeks, place any time limit on grieving, or
      imply that antidepressant medications should be prescribed. Rather, eliminating
      the BE opens the door to the same careful attention that any person suffering
      from major depressive disorder deserves and allows the clinician to provide
      appropriate education, support, hope, care, and treatment.

PMID- 24042245
TI  - Complexities of personalized medicine: how genes, drug-drug interactions, dosing
      schedules, and other factors can combine to produce clinically meaningful
      differences in a drug's effect.
AB  - Given increased knowledge from molecular biology and pharmacology, it is apparent
      that multiple factors can interact to produce clinically meaningful differences
      in a drug's effect in specific individuals (i.e., personalized medicine). This
      topic is discussed in this column using iloperidone as an example. The variables
      discussed include dose, dosing schedule, genes, drug-drug interactions, and other
      medical factors. How such variables can combine to alter a drug's effect is
      illustrated with a case example and the results of a thorough QTc study of
      iloperidone.

PMID- 24042246
TI  - Therapeutic risk management of the suicidal patient: augmenting clinical suicide
      risk assessment with structured instruments.
AB  - This column is the second in a series presenting a model for therapeutic risk
      management of the suicidal patient. As discussed in the first part of the series,
      the model involves several elements including augmenting clinical risk assessment
      with structured instruments, stratifying risk in terms of both severity and
      temporality, and developing and documenting a safety plan. This column explores
      in more detail how to augment clinical risk assessment with structured
      instruments. Unstructured clinical interviews have the potential to miss
      important aspects of suicide risk assessment. By augmenting the free-form
      clinical interview with structured instruments that demonstrate reliability and
      validity, a more nuanced and multifaceted approach to suicide risk assessment is
      achieved. Incorporating structured instruments into practice also serves a
      medicolegal function, since these instruments may become a living part of the
      medical record, establishing baseline levels of suicidal thoughts and behaviors
      and facilitating future clinical determinations regarding safety needs. We
      describe several instruments used in a multidisciplinary suicide consultation
      service, each of which has demonstrated relevance to suicide risk assessment and
      screening, ease of administration, and strong psychometric properties. In
      addition, we emphasize the importance of viewing suicide risk assessment as an
      ongoing process rather than as a singular event. Finally, we discuss special
      considerations in the evolving practice of risk assessment.

PMID- 24042247
TI  - The challenge of gun control for mental health advocates.
AB  - Mass shootings, such as the 2012 Newtown massacre, have repeatedly led to
      political discourse about limiting access to guns for individuals with serious
      mental illness. Although the political climate after such tragic events poses a
      considerable challenge to mental health advocates who wish to minimize
      unsympathetic portrayals of those with mental illness, such media attention may
      be a rare opportunity to focus attention on risks of victimization of those with
      serious mental illness and barriers to obtaining psychiatric care. Current
      federal gun control laws may discourage individuals from seeking psychiatric
      treatment and describe individuals with mental illness using anachronistic,
      imprecise, and gratuitously stigmatizing language. This article lays out
      potential talking points that may be useful after future gun violence.

PMID- 24042248
TI  - A severe and irreversible case of tardive rigid-akinetic parkinsonian syndrome:
      the role of the DaTscan.
AB  - In elderly patients, exposure to antipsychotic medication and subsequent
      withdrawal may lead to the development of persistent extrapyramidal symptoms,
      possibly including a syndrome suggested to be tardive parkinsonism. We describe a
      case in which withdrawal of antipsychotics was unexpectedly associated with
      progressive deterioration, rather than improvement, of extrapyramidal
      parkinsonian symptoms. Abnormal imaging of presynaptic dopamine transporters
      (DaTs) using single-photon emission computed tomography (SPECT) with ioflupane I
      123 (DaTscan) substantially contributed to the differential diagnosis, suggesting
      it was likely that the patient had an underlying neurodegenerative disorder that
      preceded the onset of medicationinduced parkinsonian symptoms. Our report
      illustrates how novel findings from DaTscan may assist with diagnosing the cause
      of persistent parkinsonian symptoms after antipsychotic withdrawal and provide
      insight into the controversial concept of tardive parkinsonism.

PMID- 24042249
TI  - Complicated grief and manic comorbidity in the aftermath of the loss of a son.
AB  - Based on the recommendations of the sub-workgroup on trauma and dissociative
      disorders, the American Psychiatric Association (APA) removed the "bereavement
      exclusion" from the criteria for major depression in DSM-5. In addition, proposed
      DSM-5 research criteria for persistent complex bereavement disorder (PCBD) were
      included in the new manual in a section for conditions and criteria needing
      further research. We describe a case that warranted such a diagnosis. The patient
      was a 52- year-old woman who was admitted to the inpatient unit of our clinic on
      the birthday of her son who had died 18 months earlier. She was diagnosed with a
      manic episode with psychotic symptoms according to the Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria
      and was treated accordingly. Three months after discharge, she made a suicide
      attempt and was admitted and re-assessed. During this admission, she completed
      the Inventory of Complicated Grief (ICG), the Mood-Spectrum Rating Scale (MOODS
      SR), and the Trauma and Loss Spectrum questionnaire (TALS-SR). She endorsed
      symptoms of intense yearning for her son, feelings of shock and disbelief, anger
      and bitterness related to his death, estrangement from others, auditory, tactile
      and visual hallucinations of the deceased, and intense emotional reactivity to
      memories of her son. These symptoms were sufficiently prolonged and severe to
      meet criteria for complicated grief. While complicated grief appeared to be the
      primary diagnosis for this patient, when she was diagnosed using only DSMIV-TR
      criteria, her treatment failed to address herprimary problem. This case draws
      attention to the occurrence of manic-like symptoms as well as depression-like
      manifestations following bereavement and highlights the importance of including
      the syndrome of complicated grief in the diagnostic nomenclature.

PMID- 24042250
TI  - Outcomes of specialized residential treatment for adults with obsessive
      compulsive disorder.
AB  - Cognitive-behavioral therapy (CBT) utilizing exposure and response prevention for
      obsessive- compulsive disorder (OCD) has typically been studied in the context of
      time-limited treatment conducted in outpatient settings. However, in practice,
      patients vary in their response to such treatment, and some require more
      prolonged participation to obtain optimal benefit. An intensive residential
      program is one alternative for patients who do not improve in traditional
      outpatient treatment. This naturalistic study evaluated 46 patients with a
      primary diagnosis of OCD who received intensive residential treatment between
      2004 and 2008. Patients entering the program completed assessments at admission
      and at discharge. Results indicated statistically significant improvements on all
      outcome measures, with 60.9% of patients meeting criteria for clinically reliable
      change in OCD severity and 37% achieving high end-state functioning. Specialized
      residential treatment seems effective for treatment-refractory OCD, although
      future controlled trials with larger samples are needed.

PMID- 24042251
TI  - Principles supporting dynamic clinical care teams: an American College of
      Physicians position paper.
AB  - The U.S. health care system is undergoing a shift from individual clinical
      practice toward team-based care. This move toward team-based care requires fresh
      thinking about clinical leadership and responsibilities to ensure that the unique
      skills of each clinician are used to provide the best care for the patient as the
      patient's needs dictate, while the team as a whole must work together to ensure
      that all aspects of a patient's care are coordinated for the benefit of the
      patient. In this position paper, the American College of Physicians offers
      principles, definitions, and examples to dissolve barriers that prevent movement
      toward dynamic clinical care teams. These principles offer a framework for an
      evolving, updated approach to health care delivery, providing policy guidance
      that can be useful to clinical teams in organizing the care processes and
      clinician responsibilities consistent with professionalism.

PMID- 24042252
TI  - Antidysrhythmic drug therapy for the termination of stable, monomorphic
      ventricular tachycardia: a systematic review.
AB  - OBJECTIVE: We performed a systematic review of the literature to compare the
      efficacy of different drug therapies for the termination of stable, monomorphic
      ventricular tachycardia (VT). METHODS: We searched EMBASE, MEDLINE and Cochrane
      for trials from 1965 through July 2013 using a search strategy derived from the
      following clinical question in PICO format: PATIENTS: Adults (>=18 years) with
      stable monomorphic VT; INTERVENTION: Intravenous antidysrhythmic drug;
      Comparator: Intravenous lidocaine or amiodarone; OUTCOME: Termination of VT. For
      all drug comparisons, we calculated relative risks (RR; 95% CI) and number needed
      to treat (NNT, 95% CI) between drugs. We also evaluated the methodological
      quality of the studies. RESULTS: Our search yielded 219 articles by PubMed and
      390 articles by EMBASE. 3 prospective studies (n=93 patients) and 2 retrospective
      studies (n=173 patients) met our inclusion and exclusion criteria. From the
      prospective studies, RR of VT termination of procainamide versus lidocaine was
      3.7 (1.3-10.5); ajmaline versus lidocaine, RR=5.3 (1.4-20.5); and sotalol versus
      lidocaine, RR=3.9 (1.3-11.5). From the retrospective studies: procainamide versus
      lidocaine, RR=2.2 (1.2-4.0); and procainamide versus amiodarone RR=4.3 (0.8
      23.6). All 5 reviewed studies had quality issues, including potential bias for
      randomisation and concealment. CONCLUSIONS: Based on limited available evidence
      from small heterogeneous human studies, for the treatment of stable, monomorphic
      VT, procainamide, ajmaline and sotalol were all superior to lidocaine; amiodarone
      was not more effective than procainamide.

PMID- 24042253
TI  - Routine urinalysis in patients with a blunt abdominal trauma mechanism is not
      valuable to detect urogenital injury.
AB  - OBJECTIVE: To investigate whether the routine performance of urinalysis in
      patients with a blunt trauma mechanism is still valuable. METHODS: Consecutive
      patients aged >=16 years, admitted to a Dutch Level 1 trauma centre between
      January 2008 and August 2011, were included in this retrospective cohort study.
      Results of urinalysis (erythrocytes per uL) were divided into no, microscopic or
      macroscopic haematuria. Patients were divided into four groups based on whether a
      urinalysis was performed or not, with or without imaging for urogenital injury.
      Main outcome measures were the presence of urogenital injury and whether the
      findings on urine specimen and/or imaging led to clinical consequences. RESULTS:
      A total of 1815 patients were included. The prevalence of intra-abdominal and
      urogenital injuries was 13% and 8%, respectively. In 1363 patients (75%),
      urinalysis was performed and 1031 patients (57%) underwent imaging for urogenital
      injury as well. The presence of macroscopic haematuria (n=16) led to clinical
      consequences in 73% of the patients (11 out of 15), regardless of the findings on
      imaging. Microscopic haematuria on urinalysis in combination with no findings on
      imaging led to clinical consequences in 8 out of 212 patients (4%). Microscopic
      haematuria on urinalysis in patients who did not have imaging for urogenital
      injury did not lead to clinical consequences (0 out of 54 patients; 0%). All the
      8 patients who underwent an intervention had positive findings on imaging.
      CONCLUSIONS: The results do not support the routine performance of urinalysis in
      patients admitted with a blunt trauma mechanism. Although urinalysis could be
      valuable in specific patient populations, we should consider omitting this
      investigation as a routine part of the assessment of trauma patients.

PMID- 24042254
TI  - A sticky situation.

PMID- 24042255
TI  - Bone marrow rejuvenation accelerates re-endothelialization and attenuates intimal
      hyperplasia after vascular injury in aging mice.
AB  - BACKGROUND: Aging-associated functional impairment of endothelial progenitor
      cells (EPCs) contributes to delayed re-endothelialization after vascular injury
      and exaggerated intimal hyperplasia (IH). This study tested if bone marrow (BM)
      rejuvenation accelerates post-injury re-endothelialization in aging mice. METHODS
      AND RESULTS: Using BM transplantation (BMT(Gfp->Wild)), young(Gfp) to young(Wild)
      (YTY), old(Gfp) to old(Wild) (OTO), young(Gfp) to old(Wild) (YTO), and old(Gfp)
      to young(Wild) (OTY) groups were created. After vascular injury, IH was
      significantly greater in the old group than the young group (P<0.001). BM
      rejuvenation (YTO) significantly accelerated re-endothelialization and attenuated
      IH. Compared with the OTO group, the YTY and YTO groups had earlier and greater
      EPC-derived re-endothelialization (P<0.001). The number of Sca-1(+)KDR(+) EPCs
      mobilized in the circulation induced by vascular injury was higher in young, YTO,
      and YTY mice than in old mice (P<0.05). Sca-1(+) BM cells from the young, YTO,
      and YTY groups had better migration and adhesion capacities than those from the
      old group (P<0.05). The increase in blood vascular endothelial growth factor
      (VEGF) levels after vascular injury was higher in young than in old mice. PI3K,
      Akt, and FAK pathways played a pivotal role in VEGF-associated EPC migration.
      Specifically, EPCs from young and YTO mice, compared with old mice, demonstrated
      stronger FAK phosphorylation after VEGF stimulation. CONCLUSIONS: EPCs play a
      critical role in vascular repair in aging mice. BM rejuvenation accelerates re
      endothelialization by improving EPC function.

PMID- 24042257
TI  - Selective reduction of carboxylic acids to aldehydes through manganese catalysed
      hydrosilylation.
AB  - The direct reduction of carboxylic acids to disilylacetals was achieved through a
      manganese catalyzed hydrosilylation reaction in the presence of triethylsilane
      under mild conditions, at r.t. and under UV irradiation (350 nm). The aldehydes
      were obtained in good to excellent yields after acidic hydrolysis. 

PMID- 24042259
TI  - Plk1: unexpected roles in DNA replication.
AB  - FOR20, a conserved centrosomal protein, is essential for Plk1 to localize to the
      centrosome during the S phase and regulate DNA replication. The absence of either
      Plk1 or FOR20 can stall the cell cycle by a previously unknown intra-S phase
      centrosomal checkpoint. 

PMID- 24042258
TI  - The dual PI3K/mTOR inhibitor NVP-BEZ235 enhances nab-paclitaxel antitumor
      response in experimental gastric cancer.
AB  - Gastric cancer is the second most common cause of cancer-related deaths
      worldwide. Taxanes have shown therapeutic effects against gastric cancer while
      also activating the PI3K/mTOR signaling pathway. We investigated the effects of
      NVP-BEZ235 (BEZ235), a novel dual PI3K/mTOR inhibitor, alone and in combination
      with nanoparticle albumin-bound (nab)-paclitaxel in experimental gastric cancer.
      Cell proliferation and protein expression were measured by WST-1 assay and
      immunoblotting. Tumor growth and survival studies were performed in murine
      xenografts. Phosphorylated mTOR and 4E-BP1 levels were elevated in gastric cancer
      cells and tumor tissues by nab-paclitaxel. BEZ235 effectively inhibited cell
      proliferation in vitro and provided additive effects in combination with nab
      paclitaxel. Furthermore, BEZ235 blocked the activated PI3K/mTOR pathway either
      alone or in combination with nab-paclitaxel in gastric cancer cells. BEZ235 and
      nab-paclitaxel caused an increase in PARP-1 and caspase-3 cleavage. Net local
      tumor growth inhibition for the BEZ235, nab-paclitaxel and BEZ235+nab-paclitaxel
      groups was 45.1, 77.9 and 97% compared to controls. The effects of therapy on
      intratumoral proliferation and apoptosis corresponded with tumor growth
      inhibition data. BEZ235 also caused a decrease in phospho-mTOR and phospho-Akt in
      tumor tissue lysates. Median animal survival (controls, 23 days) was 26.5 days
      after BEZ235 (p=0.227), 90.5 days after nab-paclitaxel (p=0.001) and 97 days in
      the BEZ235+nab-paclitaxel combination treatment group (p=0.001). Our findings
      suggest that BEZ235 exerts some antitumor effects against gastric cancer and
      enhances effects of nab-paclitaxel through inhibition of cell proliferation and
      modulation of the PI3K/mTOR pathway. This approach may represent a promising
      combination targeted therapy for gastric cancer.

PMID- 24042260
TI  - Lower skin cancer risk in women with higher body mass index: the women's health
      initiative observational study.
AB  - The unclear relationship of obesity to incident melanoma and nonmelanoma skin
      cancer (NMSC) risks was evaluated in the large, geographically diverse
      longitudinal, prospective Women's Health Initiative (WHI) observational study.
      Risks of melanoma and NMSC in normal weight women were compared with risks in
      overweight [body mass index (BMI) = 25-29.0 kg/m(2)] and obese (BMI >= 30
      kg/m(2)) women, using Cox proportional hazards models for melanoma and logistic
      regression for NMSC. Over a mean 9.4 years of follow-up, there were 386 melanoma
      and 9,870 NSMC cases. Risk of melanoma did not differ across weight categories (P
      = 0.86), whereas in fully adjusted models, NMSC risk was lower in overweight [OR,
      0.93; 95% confidence interval (CI), 0.89-0.99] and obese (OR, 0.85; 95% CI, 0.80
      0.91) women (P < 0.001). Excess body weight was not associated with melanoma risk
      in postmenopausal women but was inversely associated with NMSC risk, possibly due
      to lower sun exposure in overweight and obese women. This supports previous work
      demonstrating the relationship between excess body weight and skin cancer risk.

PMID- 24042261
TI  - Antidiabetic medications and the risk of colorectal cancer in patients with
      diabetes mellitus: a systematic review and meta-analysis.
AB  - BACKGROUND: Antidiabetic medications (ADM) may modify colorectal cancer risk in
      patients with diabetes mellitus. We performed a systematic review and meta
      analysis, evaluating the effect of metformin, thiazolidinediones (TZD),
      sulfonylureas, and insulin on colorectal cancer risk in diabetic patients.
      METHODS: We conducted a systematic search of multiple bibliographic databases, up
      to September 2012, for articles that evaluated exposure to metformin, TZD,
      sulfonylureas, and insulin, reported colorectal cancer risk in patients with
      diabetes mellitus, and reported OR or provided data for their estimation. Summary
      OR estimates with 95% confidence intervals (CI) were estimated using the random
      effects model. RESULTS: Fifteen studies reporting 13,871 cases of colorectal
      cancer in 840,787 patients with diabetes mellitus were included. Meta-analysis of
      observational studies showed an 11% reduction in colorectal cancer risk
      associated with metformin use (n = 9 studies; OR, 0.89; 95% CI, 0.81-0.99),
      whereas TZD use was not associated with colorectal cancer risk (n = 5 studies;
      OR, 0.96; 95% CI, 0.87-1.05). Conversely, a trend toward higher colorectal cancer
      risk was observed with sulfonylurea (n = 7 studies; OR, 1.11; 95% CI, 0.97-1.26)
      and insulin (n = 9 studies; OR, 1.33; 95% CI, 0.91-1.94) use, although these
      associations were not statistically significant. There was considerable
      heterogeneity across studies, partly explained by study location and adjustment
      for concomitant use of other ADMs. Post-hoc analysis of randomized controlled
      trials did not reveal any significant association between ADM and colorectal
      cancer risk. CONCLUSIONS: Meta-analysis of published studies supports a
      protective association between metformin use and colorectal cancer risk in
      patients with diabetes mellitus. IMPACT: Clinical trials on the chemopreventive
      effect of metformin against colorectal cancer are warranted.

PMID- 24042256
TI  - Effect of low-dose aspirin on primary prevention of cardiovascular events in
      Japanese diabetic patients at high risk.
AB  - BACKGROUND: Benefit of low-dose aspirin for primary prevention of cardiovascular
      events in diabetes remains controversial. The American Diabetes Association
      (ADA), the American Heart Association (AHA), and the American College of
      Cardiology Foundation (ACCF) recommend aspirin for high-risk diabetic patients:
      older patients with additional cardiovascular risk factors. We evaluated
      aspirin's benefit in Japanese diabetic patients stratified by cardiovascular
      risk. METHODS AND RESULTS: In the JPAD trial, we enrolled 2,539 Japanese patients
      with type 2 diabetes and no history of cardiovascular disease. We randomly
      assigned them to aspirin (81-100 mg daily) or no aspirin groups. The median
      follow-up period was 4.4 years. We stratified the patients into high-risk or low
      risk groups, according to the US recommendation: age (older; younger) and
      coexisting cardiovascular risk factors. The risk factors included smoking,
      hypertension, dyslipidemia, family history of coronary artery disease, and
      proteinuria. Most of the patients were classified into the high-risk group,
      consisting of older patients with risk factors (n=1,804). The incidence of
      cardiovascular events was higher in this group, but aspirin did not reduce
      cardiovascular events (hazard ratio [HR], 0.83; 95% confidence interval [CI]:
      0.58-1.17). In the low-risk group, consisting of older patients without risk
      factors and younger patients (n=728), aspirin did not reduce cardiovascular
      events (HR, 0.55; 95% CI: 0.23-1.21). These results were unchanged after
      adjusting for potential confounding factors. CONCLUSIONS: Low-dose aspirin is not
      beneficial in Japanese diabetic patients at high risk.

PMID- 24042262
TI  - Selective NaNO2 recognition by a simple heteroditopic salt receptor based on L
      ornithine molecular scaffold.
AB  - This paper describes the development of a simple heteroditopic salt receptor
      consisting of aza-18-crown-6 (a cation binding domain), nitrophenylurea (an anion
      binding domain) and an additional metacrylamide group appended to the carboxylic,
      alpha-amine and delta-amino groups of L-ornithine. Detailed binding studies
      showed that this receptor is capable of effectively and selectively binding NaNO2
      salt.

PMID- 24042264
TI  - Breast cancer: environmental mimicry determines metastasis to bone.

PMID- 24042265
TI  - CNS cancer: metabolic changes in brain tumours.

PMID- 24042266
TI  - Acquired hemophilia in the patient suffering from rheumatoid arthritis: case
      report.
AB  - Acquired hemophilia is a severe bleeding diathesis caused by autoantibodies
      against a coagulation factor VIII (FVIII inhibitor). Massive bleeding diathesis,
      often life threatening are observed in almost 90% of patients. In 50-60% of
      cases, inhibitor emerges spontaneously. However, there are some conditions like
      pregnancy, puerperium, autoimmune disorders or cancers that seem to induce
      acquired hemophilia. We report a case of a 49-year-old woman suffering from
      rheumatoid arthritis (RA) for several years, who was diagnosed with acquired
      hemophilia in September 2011. The patient had been treated by steroids and
      leflunomide during the last few months. At the time of diagnosis, diffuse
      bruising of the forearms and the trunk was observed. The patient was treated with
      recombinant activated factor VII, and the first-line immunosuppressive therapy
      was introduced (cyclophosphamide and prednisone). We observed the elimination of
      symptoms and the disappearance of diathesis. Significant reduction of the titer
      of inhibitor was achieved, but only partial remission was obtained. It lasted
      until the beginning of December 2011, when the titer of the inhibitor increased
      again and massive bleeding to the left lower limb occurred. It was necessary to
      administer recombinant factor VIIa together with the second-line
      immunosuppressive therapy based on the Budapest protocol. The rapid reduction of
      the diathesis and improvement of the patient's general condition was achieved as
      previously. However, still there was no complete remission. After 2 weeks of
      treatment, the titer of inhibitor diminished, and factor VIII activity increased
      slightly. Because of RA, the patient was treated with methylprednisolone in
      maintenance doses during the next few weeks. Unfortunately, after over a month,
      the increase of inhibitor titer and the decrease of FVIII level were observed
      again. Some bruises appeared. It was necessary to increase doses of
      corticosteroids to therapeutic levels and add cyclophosphamide in low doses to
      prevent the appearance of more hemorrhagic diathesis. Partial remission was
      achieved a second time at the end of April 2012. The patient was given
      methylprednisolone with chloroquine as a maintenance treatment and the control of
      RA. The titer of the inhibitor increased again in June 2012, but there were no
      signs of diathesis. In August 2012, some bruises were detected, and we decided to
      add cyclophosphamide again instead of escalating the doses of methylprednisolone
      to prevent the occurrence of side-effects of corticosteroids. Cyclophosphamide
      was given with intervals only depending on activated partial thromboplastin time.
      No further diathesis was observed in spite of the lack of remission. We were
      forced to withdrawn cyclophosphamide completely in October 2012 because of signs
      of hematuria. Fortunately, right nephrolithiasis and urinary tract infection were
      the cause of that condition. These symptoms vanished after standard supportive
      treatment. Maintenance doses of corticosteroids and chloroquine were continued as
      the main treatment. The patient's condition was good, but the titer of inhibitor
      increased over the value that had been detected at the time of diagnosis, and
      some bruises appeared again at the end of January 2013. The decision to use
      rituximab as the next-line therapy was made. This anti-CD20 monoclonal antibody
      is primarily used in the management of lymphomas. However, it has been
      successfully applied in the management of various autoimmune conditions. The
      usual treatment regime involves four separate intravenous infusions of 375 mg/m
      each, administered at weekly intervals. At the time of admission to the hospital
      in the second half of February 2013, the titer of inhibitor was dangerously high,
      almost three times more than the initial level. Fortunately, only a few bruises
      were observed, and no bypassing agents were needed. The patient was given the
      whole-planned therapy. Concomitant continuation of maintenance doses of
      corticosteroids was necessary to enforce the effect of eradication of inhibitor
      because of high levels of its titer during rituximab administration. It prevented
      the patient from massive diathesis that might occur. The laboratory tests were
      improving during the next subsequent weeks after the last dose of rituximab. Over
      a month later, a significant decrease of the titer of inhibitor and an increase
      of factor VIII activity was observed. Probably, the laboratory tests will be
      improving during the next few weeks. The patient is in outpatient care now. She
      is treated with maintenance doses of corticosteroids and chloroquine as the main
      treatment of RA. We will try to withdraw corticosteroids unless it is not
      feasible to achieve complete remission. We will have to introduce another kind of
      immunosuppressive agent in case of recurrence. 

PMID- 24042267
TI  - Structure and stability studies of mixed monolayers of saturated and unsaturated
      phospholipids under low-level ozone.
AB  - In the present study, stability and structure of single and binary mixed
      monolayers of an unsaturated phospholipid, DOPC, and a saturated phospholipid,
      DPPC-d75, on the water surface, were explored using the pi-A isotherm, atomic
      force microscopy (AFM) and sum frequency generation (SFG) vibrational
      spectroscopy in various environments. Our results demonstrated that DOPC in the
      monolayers becomes unstable after the exposure to a low concentration of ozone
      (20 +/- 10 ppb) or even to ambient laboratory air, which has a similar ozone
      level, but is stable in nitrogen or oxygen. DOPC can be selectively oxidized by a
      trace amount of ozone in the ambient environment but can be partially inhibited
      by the presence of DPPC in the monolayer. The present study provides useful
      information for understanding the physicochemical properties of the cell
      membranes. 

PMID- 24042263
TI  - Osteocytes: master orchestrators of bone.
AB  - Osteocytes comprise the overwhelming majority of cells in bone and are its only
      true "permanent" resident cell population. In recent years, conceptual and
      technological advances on many fronts have helped to clarify the role osteocytes
      play in skeletal metabolism and the mechanisms they use to perform them. The
      osteocyte is now recognized as a major orchestrator of skeletal activity, capable
      of sensing and integrating mechanical and chemical signals from their environment
      to regulate both bone formation and resorption. Recent studies have established
      that the mechanisms osteocytes use to sense stimuli and regulate effector cells
      (e.g., osteoblasts and osteoclasts) are directly coupled to the environment they
      inhabit-entombed within the mineralized matrix of bone and connected to each
      other in multicellular networks. Communication within these networks is both
      direct (via cell-cell contacts at gap junctions) and indirect (via paracrine
      signaling by secreted signals). Moreover, the movement of paracrine signals is
      dependent on the movement of both solutes and fluid through the space immediately
      surrounding the osteocytes (i.e., the lacunar-canalicular system). Finally,
      recent studies have also shown that the regulatory capabilities of osteocytes
      extend beyond bone to include a role in the endocrine control of systemic
      phosphate metabolism. This review will discuss how a highly productive
      combination of experimental and theoretical approaches has managed to unearth
      these unique features of osteocytes and bring to light novel insights into the
      regulatory mechanisms operating in bone. 

PMID- 24042268
TI  - Public Health Workforce in Switzerland: are public health workers lacking?

PMID- 24042269
TI  - Health-promoting behaviors and social support in Iranian women of reproductive
      age: a sequential explanatory mixed methods study.
AB  - OBJECTIVES: The aim of this study was to determine health-promoting behaviors and
      their determinants including social support and sociodemographic characteristics
      as well as to explore women's experience of health-promoting behaviors. METHODS:
      This sequential explanatory mixed methods study was conducted in two phases. The
      first phase was a cross-sectional study conducted on 1,359 women. Questionnaires,
      including items on sociodemographic characteristics, the HPLP-II and the PRQ85
      Part2, were completed by interview. In the second phase, 15 women who were
      identified as extreme cases participated in individual in-depth interviews.
      RESULTS: The results of the quantitative phase showed that women obtained the
      highest scores on interpersonal relations and the lowest scores on physical
      activity. Scores on the HPLP-II and all its subscales correlated significantly
      with the level of social support. In the qualitative phase, factors affecting
      health-promoting behaviors were explored and grouped into four main categories
      that included personal and socio-environmental barriers as well as personal and
      socio-environmental facilitators. CONCLUSIONS: The findings from this study
      confirm the importance of social support and modifiable variables
      (sociodemographic) that play a role in the health-promoting behaviours of women.
      These results will be useful in designing suitable interventions and strategies
      for the promotion of women's health.

PMID- 24042270
TI  - Synthesis and antitumor activity of a series of osmium(VI) nitrido complexes
      bearing quinolinolato ligands.
AB  - A series of osmium(VI) nitrido complexes supported by quinolinolato ligands have
      been prepared and they exhibit promising in vitro anti-cancer activities. These
      results establish that Os(VI)=N is a potentially versatile and promising platform
      for the design of a variety of high-valent anti-cancer drugs.

PMID- 24042271
TI  - User participation in research--real influence?

PMID- 24042272
TI  - [Blood pressure treatment--source of debate].

PMID- 24042273
TI  - [Antibiotic politics, infection control and ethics].

PMID- 24042274
TI  - [A few words about Malt's comments].

PMID- 24042275
TI  - [Sign of pain].

PMID- 24042276
TI  - [Diagnoses and the 22 July issue].

PMID- 24042277
TI  - [A.A. Dahl replies].

PMID- 24042278
TI  - [Who knows what is best for the patient?].

PMID- 24042279
TI  - [Relatives right to participate].

PMID- 24042280
TI  - [The relatives' role].

PMID- 24042281
TI  - [Professionalism].

PMID- 24042282
TI  - [A good body physician is the most important].

PMID- 24042285
TI  - [How large is the effect of the intervention?].

PMID- 24042286
TI  - [R. Ulvik replies].

PMID- 24042287
TI  - [New diagnostic systems--new reality?].

PMID- 24042288
TI  - [It's time to think differently!].

PMID- 24042289
TI  - [MRSA in nursing homes in Oslo].

PMID- 24042290
TI  - [Choice of drug in hypertension].

PMID- 24042291
TI  - [Hypertension in healthy people over 80 should be treated].

PMID- 24042294
TI  - [Cases of MRSA in nursing homes in Oslo 2005-11].
AB  - BACKGROUND: The number of infections caused by MRSA has increased substantially
      in Norway in the past decade. It is an objective to prevent MRSA from becoming
      established in nursing homes and hospitals. The purpose of the article is to
      describe the features of the development of MRSA cases found in nursing homes in
      Oslo. MATERIALS AND METHOD: We carried out a retrospective study of registered
      cases of MRSA (both sufferers and carriers) in Oslo in 2005-11. Data were
      obtained from the City of Oslo municipal health services' MRSA database and from
      genotyping carried out at Akershus University Hospital. RESULTS: The annual
      number of cases of MRSA found in Oslo increased during the period 2005-11 from 92
      in 2005 to 268 in 2011, a total of 1198 cases. Of these, 224 cases (19%) were
      registered in nursing homes, distributed among 22 institutions, 158 residents and
      66 staff, with an average of 32 cases annually (14-58 spread). Twenty-eight of 50
      nursing homes had no cases of MRSA, while 159 of the cases were related to
      outbreaks of MRSA. Three of 20 outbreaks affected residents only. The nursing
      home isolates consisted of 40 different spa types, of which 160 (71%) of the
      isolates were clustered in three clonal complexes. The most common spa type t304
      was found in 116 (52%) of the cases. INTERPRETATION: Cases of MRSA in Oslo in
      total increased sharply from 2005 to 2011, while the number of cases in nursing
      homes was stable. It is, however, uncertain whether this reflects the actual
      incidence.

PMID- 24042295
TI  - Treatment of cerebral infarction at the stroke unit in Bodo 2011-12.
AB  - BACKGROUND: The regional health enterprises wish to increase the proportion of
      cerebral infarction patients who receive intravenous thrombolytic therapy. We
      have identified the reasons why only very few patients received such treatment
      during 2011-12. We also wished to assess the benefits of ECG telemetry in the
      examination of the patients. MATERIAL AND METHOD: With permission from the
      enterprise's own data protection officer, we analysed data for all patients
      discharged from the stroke unit at the Department of Neurology, Nordland
      Hospital, after a cerebral infarction (diagnostic code I63) in the period from 1
      January 2011 to 30 April 2012. RESULTS: Of a total of 180 patients admitted
      directly to the stroke unit, only 12 (6.7%) received intravenous thrombolytic
      therapy. The main reasons why such treatment was not provided include late
      arrival at the hospital (n = 91: 50%) and an unknown time of symptom onset (n =
      60: 33%). ECG telemetry detected atrial fibrillation in 27 of the 112 patients
      examined (24%), which meant that anticoagulation treatment was provided to 22
      patients who otherwise would have received platelet inhibitors. INTERPRETATION:
      Half of all patients with cerebral infarction arrived in the hospital too late
      for provision of intravenous thrombolytic therapy, and in one-third the time of
      onset could not be determined. In many patients, ECG telemetry led to changes in
      the choice of secondary prophylaxis.

PMID- 24042296
TI  - [Necrosis in fingers and toes following local anaesthesia with adrenaline--an
      urban legend?].
AB  - BACKGROUND: It is often maintained that a local anaesthetic (usually lidocaine)
      with adrenaline must not be used in fingers and toes because it may cause
      necrosis due to vascular spasm in end arteries. This review article is an attempt
      to find evidence to support this warning. METHOD: Relevant literature was found
      by means of searches in PubMed limited downwards to 1946 and in EMBASE from 1980
      to 2012, and in reference lists. RESULTS: Five review articles on finger necrosis
      following local anaesthesia concluded that lidocaine with adrenaline does not
      entail a risk of ischaemic injury. One article found 48 reported cases of finger
      necrosis in the period 1880 to 2000. Most were from the first half of the 1900s,
      and none involved lidocaine. Gangrene of part of the finger tip has subsequently
      been described in one patient with Raynaud's syndrome. No cases of necrosis have
      been described in a large number of reported accidents in which EpiPen injections
      contained the same quantity of adrenaline as is found in 60 ml lidocaine with
      adrenaline. Over a quarter of a million reports have been made of operations on
      feet, hands, fingers and toes anaesthetised with lidocaine with adrenaline
      without resulting necrosis. INTERPRETATION: There are no grounds for the warning
      against using lidocaine with adrenaline in fingers and toes. This anaesthetic
      offers considerable practical advantages. Care should be taken with infected
      fingers or fingers with poor circulation.

PMID- 24042298
TI  - [Prioritization belong in politics].

PMID- 24042297
TI  - [Cardioprotective treatment during adjuvant cancer therapy].
AB  - BACKGROUND: Cardiac dysfunction in the form of reduced systolic and/or diastolic
      left ventricular function after adjuvant cancer therapy has recently attracted
      increasing attention. The best-known cardiotoxic agents are anthracyclines and
      the recombinant antibody trastuzumab. Patients treated with radiotherapy to the
      thorax are liable to develop coronary artery disease. There are no official
      guidelines for the preventive treatment of cardiac dysfunction induced by
      chemotherapy, antibody therapy or radiotherapy. The purpose of this article is to
      provide an overview of cardiac dysfunction caused by adjuvant cancer therapies
      and to review possible preventive therapeutic principles. MATERIAL AND METHOD:
      This article is based on a review of the literature derived from a search in
      PubMed. RESULTS: 27% of those treated with anthracyclines and trastuzumab may
      develop some degree of cardiac dysfunction. The figure for patients receiving
      radiotherapy to the thorax is more uncertain. Small-scale studies suggest that
      anthracycline-induced cardiac dysfunction can be prevented wholly or partially by
      blocking the renin-angiotensin-aldosterone system and by beta-adrenergic
      blockade. As yet, there are no results of prospective studies on cardiopreventive
      treatment during trastuzumab therapy or thoracic radiotherapy. INTERPRETATION:
      There is a need for randomised, placebo-controlled studies of homogeneous groups
      of patients in order to determine whether treatment with cardioprotective
      medication in parallel with chemotherapy, antibody therapy or radiotherapy can
      prevent or reduce cardiac dysfunction.

PMID- 24042299
TI  - [Does budget consequences control Norwegian reimbursement priorities?].

PMID- 24042300
TI  - Trans fat can be a hidden health risk.

PMID- 24042301
TI  - [Physicians to the people].

PMID- 24042302
TI  - Quarantine--not only about disease.

PMID- 24042304
TI  - Does hyperoxic recovery during cross-country skiing team sprints enhance
      performance?
AB  - PURPOSE: This study aimed to determine the acute responses of breathing oxygen
      enriched air during the recovery periods of a simulated 3 * 3-min cross-country
      skiing team sprint competition at simulated low altitude. METHODS: Eight well
      trained male endurance athletes performed two 3 * 3-min team sprint simulations
      on a double-poling ergometer at simulated altitude set at ~ 1800 m. During the
      recovery periods between the 3 * 3-min sprints, all the athletes inhaled either
      hyperoxic (FiO2 = 1.00) or hypoxic (FiO2 ~ 0.165) air in randomized and single
      blind order. The mean total power output (P(mean tot)) and the mean power output
      of each sprint (P(mean) 1,2,3) were determined. Perceived exertion, capillary
      oxygen saturation of hemoglobin, partial pressure of oxygen, and blood lactate
      concentration were measured before and after all the sprints. RESULTS: No
      differences in P(mean tot) were found between hyperoxic (198.4 +/- 27.1 W) and
      hypoxic (200.2 +/- 28.0 W) recovery (P = 0.57, effect size [d] = 0.07). P(mean)
      1,2,3 (P > 0.90, d = 0.04-0.09) and RPE (P > 0.13, d = 0.02-0.63) did not differ
      between hyperoxic and hypoxic recovery. The partial pressure of oxygen (P < 0.01,
      d = 0.06-5.45) and oxygen saturation (P < 0.01, d = 0.15-5.40) during hyperoxic
      recovery were higher than those during hypoxic recovery. The blood lactate
      concentration was also lower directly after the third sprint (P = 0.03, d = 0.54)
      with hyperoxic recovery. CONCLUSION: Results indicate that trained endurance
      athletes who inhale 100% oxygen during recovery periods in a cross-country skiing
      team sprint at low altitude do not exhibit enhanced performance despite the
      improvement in the key physiological variables of endurance performance.

PMID- 24042305
TI  - Pulmonary mechanics and gas exchange during exercise in Kenyan distance runners.
AB  - PURPOSE: The purpose of this study was to determine arterial blood gases, the
      mechanical limits for generating expiratory flow and the work performed by the
      respiratory muscles during treadmill exercise in Kenyan runners. METHODS: Kenyan
      runners (10 men and 4 women; mean +/- SD age = 25.2 +/- 1.3 yr) were instrumented
      with a radial artery catheter, an esophageal balloon-tipped catheter, and an
      esophageal temperature probe for the determination of blood gases, the work of
      breathing and core temperature, respectively. Testing occurred at 1545 m above
      sea level. RESULTS: There were significant decreases in the arterial partial
      pressure of O2 and oxyhemoglobin saturation and a widening of the alveolar-to
      arterial difference in O2 from rest to peak exercise. The mechanical work of
      breathing increased with increasing minute ventilation and was commensurate with
      values expected for treadmill running in elite athletes. During heavy exercise,
      significant expiratory flow limitation was present in half of the subjects while
      the remaining subjects demonstrated impending flow limitation. CONCLUSIONS:
      Pulmonary system limitations were present in Kenyan runners in the form of
      exercise-induced arterial hypoxemia, expiratory flow limitation, and high levels
      of respiratory muscle work. It appears that Kenyan runners do not possess a
      pulmonary system that confers a physiological advantage.

PMID- 24042306
TI  - Prior upper body exercise reduces cycling work capacity but not critical power.
AB  - PURPOSE: This study examined whether metabolite accumulation, induced by prior
      upper body exercise, affected the power-duration relationship for leg cycle
      ergometry. METHODS: Seven males performed, to the limit of tolerance and both
      without (L) and with (AL) prior severe-intensity arm-cranking exercise, an
      incremental cycling test and four constant power cycling tests to determine the
      parameters of the power-duration relationship: critical power (CP) and W'.
      RESULTS: At the onset of cycling exercise plasma lactate (L vs AL: 1.2 +/- 0.1 vs
      11.6 +/- 2.9 mEq . L) and hydrogen ion (40.4 +/- 1.3 vs 53.1 +/- 4.3 nEq . L),
      concentrations were higher during AL compared with L, whereas the strong ion
      difference (37.8 +/- 1.8 vs 32.4 +/- 2.0 mEq . L) and bicarbonate concentration
      (25.7 +/- 0.7 vs 18.3 +/- 1.9 mEq . L) were lower during AL compared with L (P <
      0.01). During incremental exercise, maximum cycling power (358 +/- 15 vs 332 +/-
      21 W) and peak oxygen uptake (VO2peak) (4.31 +/- 0.36 vs 3.71 +/- 0.44 L . min)
      were lower during AL compared with L (P < 0.05). The rate of increase in plasma
      potassium concentration during constant power cycling was greater during AL
      compared with L (0.09 +/- 0.08 vs 0.14 +/- 0.13 mEq . L . min) (P < 0.05), and
      exercise duration was 35 +/- 15% shorter (P < 0.01). CP was not different between
      L and AL (267 +/- 19 vs 264 +/- 20 W), whereas W' was lower in AL (17.3 +/- 5.7
      vs 11.8 +/- 4.2 kJ) (P < 0.01). CONCLUSION: The reduced W' after prior upper body
      exercise indicates that the magnitude of W' is partly dependent on metabolite
      accumulation.

PMID- 24042307
TI  - Exercise in patients with non-small cell lung cancer.
AB  - PURPOSE: This study aimed to evaluate the safety, feasibility, and effects of an
      8-wk combined resistance and endurance exercise program in patients with advanced
      non-small cell lung cancer (NSCLC) during in- and outpatient care. METHODS: In
      this intervention study, 40 patients with predominantly advanced NSCLC receiving
      simultaneous or sequential radiochemotherapy or chemotherapy alone were enrolled.
      For a period of 8 wk, patients were instructed to exercise at least five times
      per week during the inpatient setting and at least three times per week in the
      outpatient setting. Physical performance status (endurance capacity: 6-min walk
      test; strength capacity: handheld dynamometry), quality-of-life (Functional
      Assessment of Cancer Therapy-Lung), fatigue (Multidimensional Fatigue Inventory),
      and depression (Patient Health Questionnaire) were assessed at baseline (T0),
      after the exercise intervention (T1), and at a follow-up time point 8 wk later
      (T2). The primary end point was adequate adherence (feasibility) defined as
      completing at least two training sessions per week during a minimum of 6 wk.
      RESULTS: Of 40 patients, 31 (77.5%) completed the postexercise assessment (T1)
      and 22 (55%) completed follow-up (T2). The stages were IIA (5%), IIIA (8%), IIIB
      (20%), and IV (67%), and the median age was 63 yr (range = 22-75 yr). Overall,
      adherence was 82% for those patients who completed T1, and 55% of the 40
      participating patients fulfilled the adequate adherence criterion. Those who
      completed the intervention showed a significant improvement in the 6-min walk
      distance and in knee, elbow, and hip muscle strength after the intervention (T1).
      Quality of life, fatigue, and depression scores remained stable or declined
      slightly. Significant improvements in knee-muscle strength were also observed at
      T2. CONCLUSIONS: Exercise training is feasible in advanced and metastatic NSCLC
      patients during anticancer treatment. In this pilot study, endurance and strength
      capacity improved over time, indicating the rehabilitative importance of the
      applied intervention. To investigate the potential impact of exercise training in
      this patient group, a larger randomized trial is warranted.

PMID- 24042308
TI  - Exercise as medicine in the management of pancreatic cancer: a case study.
AB  - INTRODUCTION: Given the poor prognosis for patients diagnosed with pancreatic
      cancer, therapies that enhance the ability to tolerate adjuvant treatments,
      reduce the loss of physical functioning and optimize quality of life are
      critically important. Exercise may represent such a therapy; however, no previous
      research has investigated the potential impact of exercise on outcomes in
      pancreatic cancer patients. PURPOSE: This study aimed to determine the safety and
      efficacy of a 6-month supervised exercise program in a pancreatic cancer patient
      undergoing adjuvant treatment. METHODS: A case study was performed on a 49-yr-old
      male diagnosed with stage IIb pancreatic cancer. The patient had surgery (Whipple
      resection) followed by adjuvant chemotherapy (gemcitabine and fluorouracil) and
      radiotherapy (45 Gy). The patient initiated a supervised exercise program
      involving twice weekly resistance and aerobic exercise sessions during adjuvant
      therapy. Outcomes were assessed at baseline and after 3 and 6 months of exercise.
      RESULTS: The exercise program was well tolerated with 73% attendance throughout
      the 6 months. No treatment toxicities prevented the patient from complying with
      adjuvant treatment plans. Considerable improvements were observed at both 3- and
      6-month assessment points for all measures of physical capacity and functional
      ability, lean mass, physical activity levels, general health and disease-specific
      quality of life, cancer-related fatigue, sleep quality, and psychological
      distress. CONCLUSIONS: In this first reported clinical case, exercise led to
      improvements in a variety of patient outcomes during adjuvant therapy for
      pancreatic cancer. This initial evidence has important clinical implications,
      indicating that exercise may be an effective adjunct therapy for the management
      of pancreatic cancer. Future trials are needed to confirm and expand our initial
      findings.

PMID- 24042309
TI  - ActiGraphTM activity monitors: "the firmware effect".
AB  - PURPOSE: The objective of this study is to examine the effect of different
      firmware versions on ActiGraphTM counts from the laboratory, field, and
      mechanical shaker testing. METHODS: Counts from 5 GT3X and 7 GT1M firmware
      versions were compared in this study. Monitors uploaded with these firmware
      versions were worn on the hip by 15 participants (age = 24.9 +/- 5.0 yr, BMI=
      23.9 +/- 2.4 kg . m(-2)) who performed laboratory-based treadmill (walking: 1.5,
      3.0 and 4.5 mph; running: 6 mph) and simulated free-living activities (sitting,
      self-paced walking, filing papers, dusting, vacuuming, and cleaning the room).
      Testing was also conducted during 1 d of free living and using orbital mechanical
      shaker testing at 0.7, 1.3, 2.0, and 3.0 Hz. Intermonitor comparisons for
      vertical, anteroposterior, mediolateral, and triaxial vector magnitude counts
      were conducted using one-way ANOVA and post hoc pairwise comparisons (P < 0.05).
      RESULTS: Vertical counts during treadmill walking at 1.5 mph from the GT1M
      monitor with firmware version 1.1.0. were significantly greater (P < 0.05; 75%)
      than output from the monitor with firmware version 1.3.0. Shaker testing revealed
      statistically significant differences in vertical and lateral counts. Although
      there were no significant differences among activity counts in the free-living
      comparisons, firmware version 1.1.0. produced the highest vertical counts during
      this protocol. CONCLUSION: Greater sensitivity of firmware version 1.1.0. to low
      frequency sedentary activities resulted in greater counts than other firmware
      versions. It is recommended that before releasing new firmware, ActiGraphTM
      perform both human and mechanical shaker testing to verify comparability in
      outputs between new and previous firmware versions.

PMID- 24042310
TI  - Longitudinal person-related determinants of physical activity in young adults.
AB  - PURPOSE: This study aimed to examine the longitudinal associations of person
      related factors with physical activity (PA) behavior in young adults. METHODS: We
      analyzed longitudinal self-reported time spent in moderate-intensity PA (MPA; 4-7
      METs) and vigorous-intensity PA (VPA; >7 METs) from 499 young adults (49% male)
      who participated in the Amsterdam Growth and Health Longitudinal Study at the age
      of 21, 27, 32, and 36 yr. Sociodemographic factors (i.e., marital and employment
      status), physical factors (i.e., skinfolds, aerobic fitness, neuromotor fitness,
      back problems, and general health status), psychological factors (i.e., problem
      and emotion focused coping, mild health complaints, and personality), and
      behavioral factors (i.e., alcohol consumption, smoking, and energy intake) were
      assessed at each time point. We performed sex-specific univariable and
      multivariable generalized estimating equations. RESULTS: Men and women with
      higher aerobic fitness were more moderately and vigorously active. Not having
      paid work was associated with more MPA in both men and women. Men with part-time
      paid work, lower scores on dominance, higher scores on hostility, and above
      moderate alcohol consumption (i.e., >=140 g of alcohol per week) were more
      moderately active. Divorced women and those with better physical flexibility
      spent more time in MPA. Men having full-time paid work, with a good general
      health status and nonsmokers, were more vigorously active. Women being
      married/living together, who had better physical flexibility, lower scores on
      inadequacy, higher scores on dominance, and low caloric intake (around 2000
      kcal.d) were more vigorously active. CONCLUSION: Several sociodemographic,
      physical, psychological, and behavioral factors were associated with PA in Dutch
      young adults. Determinants were different for MPA and VPA and for men and women.

PMID- 24042311
TI  - Why don't most runners get knee osteoarthritis? A case for per-unit-distance
      loads.
AB  - Peak knee joint contact forces ("loads") in running are much higher than they are
      in walking, where the peak load has been associated with the initiation and
      progression of knee osteoarthritis. However, runners do not have an especially
      high risk of osteoarthritis compared with nonrunners. This paradox suggests that
      running somehow blunts the effect of very high peak joint contact forces, perhaps
      to provide a load per unit distance (PUD) traveled that is relatively low.
      PURPOSE: This study aimed to compare peak and PUD knee joint loads between human
      walking and running. METHODS: Fourteen healthy adults walked and ran at self
      selected speeds. Ground reaction force and motion capture data were measured and
      combined with inverse dynamics and musculoskeletal modeling to estimate the peak
      knee joint loads, PUD knee joint loads, and the impulse of the knee joint contact
      force for each gait with a matched-pair (within-subject) design. RESULTS: The
      peak load was three times higher in running (8.02 vs 2.72 body weight, P <
      0.001), but the PUD load did not differ between running and walking (0.80 vs 0.75
      body weight per meter, P = 0.098). The impulse of the joint contact force was
      greater for running than for walking (1.30 vs 1.04 body weight per second, P <
      0.001). The peak load increased with increasing running speed, whereas the PUD
      load decreased with increasing speed. CONCLUSIONS: Compared with walking, the
      relatively short duration of ground contact and relatively long length of strides
      in running seem to blunt the effect of high peak joint loads, such that the PUD
      loads are no higher than that in walking. Waveform features other than or in
      addition to the peak value should be considered when studying joint loading and
      injuries.

PMID- 24042312
TI  - Effects of dynamic stretching on strength, muscle imbalance, and muscle
      activation.
AB  - PURPOSE: This study aimed to examine the acute effects of dynamic stretching on
      concentric leg extensor and flexor peak torque, eccentric leg flexor peak torque,
      and the conventional and functional hamstring-quadriceps (H:Q) ratios. METHODS:
      Twenty-one women (mean +/- SD age = 20.6 +/- 2.0 yr, body mass = 64.5 +/- 9.3 kg,
      height = 164.7 +/- 6.5 cm) performed maximal voluntary isokinetic leg extension,
      flexion, and eccentric hamstring muscle actions at the angular velocities of 60
      degrees .s and 180 degrees .s before and after a bout of dynamic hamstring and
      quadriceps stretching as well as a control condition. RESULTS: Leg flexion peak
      torque decreased under both control (mean +/- SE for 60 degrees s = 75.8 +/- 4.0
      to 72.4 +/- 3.7 N.m, 180 degrees .s = 62.1 +/- 3.2 to 59.1 +/- 3.1 N.m) and
      stretching (60 degrees .s = 73.1 +/- 3.9 to 65.8 +/- 3.3 N.m, 180 degrees .s =
      61.2 +/- 3.3 to 54.7 +/- 2.6 N.m) conditions, whereas eccentric hamstring peak
      torque decreased only after the stretching (60 degrees .s = 87.3 +/- 5.1 to 73.3
      +/- 3.6 N.m, 180 degrees .s = 89.2 +/- 4.4 to 77.0 +/- 3.4 N.m) intervention (P
      <= 0.05). Stretching also caused a decrease in conventional H:Q (60 degrees .s =
      0.58 +/- 0.02 to 0.54 +/- 0.02, 180 degrees .s = 0.67 +/- 0.02 to 0.61 +/- 0.03)
      and functional H:Q ratios (60 degrees .s = 0.69 +/- 0.03 to 0.60 +/- 0.03, 180
      degrees .s = 1.00 +/- 0.06 to 0.60 +/- 0.03) (P <= 0.05). CONCLUSIONS: Because
      dynamic stretching reduced concentric and eccentric hamstring strength as well as
      the conventional and functional H:Q ratios, fitness and allied-health
      professionals may need to be cautious when recommending dynamic rather than
      static stretching to maintain muscle force.

PMID- 24042313
TI  - Respiratory inductance plethysmography-a rationale for validity during exercise.
AB  - INTRODUCTION: The aim of this study was to provide a rationale for future
      validations of a priori calibrated respiratory inductance plethysmography (RIP)
      when used under exercise conditions. Therefore, the validity of a posteriori
      adjusted gain factors and accuracy in resultant breath-by-breath RIP data
      recorded under resting and running conditions were examined. METHODS: Healthy
      subjects, 98 men and 88 women (mean +/- SD: height = 175.6 +/- 8.9 cm, weight =
      68.9 +/- 11.1 kg, age = 27.1 +/- 8.3 yr), underwent a standardized test protocol,
      including a period of standing still, an incremental running test on treadmill,
      and multiple periods of recovery. Least square regression was used to calculate
      gain factors, respectively, for complete individual data sets as well as several
      data subsets. In comparison with flowmeter data, the validity of RIP in breathing
      rate (fR) and inspiratory tidal volume (VTIN) were examined using coefficients of
      determination (R). Accuracy was estimated from equivalence statistics. RESULTS:
      Calculated gains between different data subsets showed no equivalence. After gain
      adjustment for the complete individual data set, fR and VTIN between methods were
      highly correlated (R = 0.96 +/- 0.04 and 0.91 +/- 0.05, respectively) in all
      subjects. Under conditions of standing still, treadmill running, and recovery,
      86%, 98%, and 94% (fR) and 78%, 97%, and 88% (VTIN), respectively, of all breaths
      were accurately measured within +/- 20% limits of equivalence. CONCLUSION: In
      case of the best possible gain adjustment, RIP confidentially estimates tidal
      volume accurately within +/- 20% under exercise conditions. Our results can be
      used as a rationale for future validations of a priori calibration procedures.

PMID- 24042314
TI  - Chromogranin A, Ki-67 index and IGF-related genes in patients with neuroendocrine
      tumors.
AB  - Chromogranin A (CgA) and the Ki-67 proliferation index are considered as
      important biochemical and pathological markers for clinical behaviour of
      gastroenteropancreatic neuroendocrine tumors (GEP NETs), respectively. The IGF
      system has been suggested as an important regulator of GEP NET proliferation and
      differentiation. A possible relationship between serum CgA (sCgA), Ki-67
      proliferation index, and expression of IGF-related genes in patients with GEP
      NETs has not been demonstrated yet. This study investigates the relationship
      between sCgA, the Ki-67 proliferation index, and the expression of IGF-related
      genes in GEP NET tissues and their relation with 5-year survival. Tumor and blood
      samples from 22 GEP NET patients were studied. TUMORAL MRNA EXPRESSION OF IGF
      RELATED GENES (IGFS: IGF1, IGF2; IGF receptors: IGF1R, IGF2R; insulin receptors:
      subtype A (IR-A) and B (IR-B); IGF-binding proteins (IGFBPs): IGFBP1, IGFBP2,
      IGFBP3, and IGFBP6) was measured using quantitative RT-PCR. Ki-67 proliferation
      index was determined using immunohistochemistry. sCgA was measured with ELISA.
      Five-year survival in patients with nonelevated sCgA (n=11) was 91 vs 46% in
      patients with elevated sCgA (n=11) (P=0.006). IR-A mRNA expression was
      significantly higher in tumors obtained from patients with elevated sCgA than in
      those from patients with nonelevated sCgA (6.42+/-2.08 vs 2.60+/-0.40; P=0.04).
      This data suggests that sCgA correlates well with 5-year survival of GEP NET
      patients, and that IR-A mRNA expression correlates well with tumor mass in GEP
      NET patients.

PMID- 24042315
TI  - Stem cell antigen-1 in skeletal muscle function.
AB  - Stem cell antigen-1 (Sca-1) is a member of the Ly-6 multigene family encoding
      highly homologous, glycosyl-phosphatidylinositol-anchored membrane proteins. Sca
      1 is expressed on muscle-derived stem cells and myogenic precursors recruited to
      sites of muscle injury. We previously reported that inhibition of Sca-1
      expression stimulated myoblast proliferation in vitro and regulated the tempo of
      muscle repair in vivo. Despite its function in myoblast expansion during muscle
      repair, a role for Sca-1 in normal, post-natal muscle has not been thoroughly
      investigated. We systematically compared Sca-1-/- (KO) and Sca-1+/+ (WT) mice and
      hindlimb muscles to elucidate the tissue, contractile, and functional effects of
      Sca-1 in young and aging animals. Comparison of muscle volume, fibrosis, myofiber
      cross-sectional area, and Pax7+ myoblast number showed little differences between
      ages or genotypes. Exercise protocols, however, demonstrated decreased stamina in
      KO versus WT mice, with young KO mice achieving results similar to aging WT
      animals. In addition, KO mice did not improve with practice, while WT animals
      demonstrated conditioning over time. Surprisingly, myomechanical analysis of
      isolated muscles showed that KO young muscle generated more force and experienced
      less fatigue. However, KO muscle also demonstrated incomplete relaxation with
      fatigue. These findings suggest that Sca-1 is necessary for muscle conditioning
      with exercise, and that deficient conditioning in Sca-1 KO animals becomes more
      pronounced with age. 

PMID- 24042316
TI  - Organizing a PhD symposium--an inside view. Setting up a scientific meeting is
      challenging--a PhD symposium offers its own unique opportunities and pitfalls.

PMID- 24042317
TI  - Rho/Rho-associated kinase pathway in glaucoma (Review).
AB  - The Rho/ROCK pathway plays important roles in the modulation of the cytoskeletal
      integrity of cells, the synthesis of extracellular matrix components in the
      aqueous humor outflow tissue and the permeability of Schlemm's canal endothelial
      cells. The activation of the Rho/ROCK pathway results in trabecular meshwork (TM)
      contraction, and the inhibition of this pathway would provoke relaxation of TM
      with subsequent increase in outflow facility and, thereby, decrease intraocular
      pressure (IOP). ROCK inhibitors also serve as potent anti-scarring agents via
      inhibition of transdifferentiation of tenon fibroblasts into myofibroblasts.
      Furthermore, the RhoA/ROCK pathway is involved in optic nerve neuroprotection.
      Inactivation of Rho/ROCK signaling increase ocular blood flow, improve retinal
      ganglion cell (RGC) survival and promote RGC axon regeneration. Considering the
      IOP modulation, potent bleb anti-scarring effect and neuroprotective properties
      of ROCK inhibitors, the Rho/ROCK pathway is an attractive target for anti
      glaucoma therapy, and it may be used for human therapy in the near future. 

PMID- 24042319
TI  - Fumbling toward the future: internal medicine and clinical care teams.

PMID- 24042318
TI  - Extreme binge drinking among 12th-grade students in the United States: prevalence
      and predictors.
AB  - IMPORTANCE: The prevalence of underage alcohol use has been studied extensively,
      but binge drinking among youth in the United States is not yet well understood.
      In particular, adolescents may drink much larger amounts than the threshold (5
      drinks) often used in definitions of binge drinking. Delineating various levels
      of binge drinking, including extreme levels, and understanding predictors of such
      extreme binge drinking among youth will benefit public health efforts. OBJECTIVE:
      To examine the prevalence and predictors of 5+ (>=5 drinks) binge drinking and of
      10+ (>=10 drinks) and 15+ (>=15 drinks) extreme binge drinking among 12th graders
      in the United States. DESIGN, SETTING, AND PARTICIPANTS: A nonclinical nationally
      representative sample of high school seniors in the annual Monitoring the Future
      study between 2005 and 2011. The sample included 16,332 high school seniors
      (modal age, 18 years) in the United States. Response rates were 79.1% to 84.7%.
      MAIN OUTCOMES AND MEASURES: Prevalence of consuming 5 or more, 10 or more, and 15
      or more drinks in a row in the last 2 weeks. RESULTS: Between 2005 and 2011, a
      total of 20.2% of high school seniors reported 5+ binge drinking, 10.5% reported
      10+ extreme binge drinking, and 5.6% reported 15+ extreme binge drinking in the
      last 2 weeks. Rates of 5+ binge drinking and 10+ extreme binge drinking have
      declined since 2005, but rates of 15+ extreme binge drinking have not
      significantly declined. Students with college-educated parents were more likely
      to consume 5 or more drinks but were less likely to consume 15 or more drinks
      than students whose parents were not college educated. Students from more rural
      areas were more likely than students from large metropolitan areas to consume 15
      or more drinks. Substance-related attitudes, socializing with substance-using
      peers, the number of evenings out with friends, and other substance use
      (cigarettes and marijuana) predicted all 3 levels of binge and extreme binge
      drinking. CONCLUSIONS AND RELEVANCE: Binge drinking at the traditionally defined
      5+ drinking level was common among high school seniors representative of all 12th
      graders in the contiguous United States. A significant segment of students also
      reported extreme binge drinking at levels 2 and 3 times higher. These data
      suggest the importance of assessing multiple levels of binge drinking behavior
      and their predictors among youth to target effective screening and intervention
      efforts.

PMID- 24042320
TI  - Amiodarone-induced thyrotoxicosis late after amiodarone withdrawal.
AB  - BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) may develop long after
      amiodarone withdrawal. This study sought to determine the incidence and clinical
      characteristics of AIT after amiodarone withdrawal. METHODS AND RESULTS: The
      incidence and clinical characteristics of AIT were examined retrospectively in 71
      patients (51 males, mean age 65+/-13 years) whose amiodarone therapy had been
      discontinued after at least 1 month of administration. Five (7%) patients
      developed AIT late after amiodarone withdrawal (11+/-3 months): 2 patients
      exhibited exacerbation of heart failure by atrial fibrillation, 2 developed
      dyspnea on exertion, and 1 patient was asymptomatic. The patients who developed
      AIT had a high incidence of amiodarone-induced hypothyroidism during amiodarone
      therapy (100 vs. 24%, P=0.002), had received amiodarone therapy for longer (76+/
      86 months vs. 16+/-22 months, P<0.001), with a larger cumulative dose (271.1+/
      268.5 g vs. 63.4+/-86.5 g, P<0.001) compared with those who did not. In all 5
      patients, AIT resolved spontaneously within 5 months without the use of steroids.
      CONCLUSIONS: Occurrence of amiodarone-induced hypothyroidism during amiodarone
      therapy and long duration of therapy may be cautionary markers of late AIT.

PMID- 24042321
TI  - Survey of reoperation indications in tetralogy of fallot in Japan.
AB  - BACKGROUND: Although the survival rate for repaired Tetralogy of Fallot (TOF) is
      dramatically improving, anatomical and functional residua and sequelae followed
      by arrhythmias and sudden death are still challenging issues to be resolved.
      Reoperation can reduce the incidence of arrhythmias and sudden death, but there
      is no consensus on the indications of reoperation for patients with TOF,
      especially in Japan. METHODS AND RESULTS: A cross-sectional questionnaire survey
      of reoperation indications in patients with TOF was performed through a Japanese
      multicenter study. The questionnaire, which focused on the number of repaired TOF
      patients aged >15 years old, reoperation indications and management, was sent to
      the institutions belonging to Japanese Society for Adult Congenital Heart
      Disease. In total, 41.5% (78/188) of the institutions replied. The total number
      of repaired TOF patients was 4,010, and sudden cardiac death was observed in
      45.236/4,010 (5.9%) experienced reoperation. Pulmonary stenosis (32%) and
      pulmonary regurgitation (29%) were the most common reasons for reoperation. There
      were only 2 implantable cardioverter defibrillator or resynchronization therapy
      defibrillator implantations. The physiological/anatomical indications of
      reoperation differed among the hospitals. CONCLUSIONS: Approximately 1.1% of
      patients suffered sudden death and 6% of repaired TOF patients had reoperation.
      The indications of reoperation, however, varied among the institutions.
      Therefore, detailed information for each case of sudden death or reoperation
      should be collected and analyzed in order to establish guidelines for
      reoperation.

PMID- 24042323
TI  - [Abstracts of the 48th Annual Meeting of the German Society for Neuroradiology
      joint Annual Meeting of the DGNR and OGNR. October 10-12, 2013. Gurzenich, Koln,
      Germany].

PMID- 24042322
TI  - Selectively recognizing organic semiconducting molecules on solid state molecular
      cages based on ZnOTCPP.
AB  - In this study, we constructed a novel solid state supramolecular system-the
      molecular cage ZnOTCPP, based on an inorganic/organic hybrid nanostructure,
      through the assembly of 5,10,15,20-tetra(3-carboxyphenyl)porphyrin (TCPP) onto
      the surfaces of ZnO nanorod (NR) arrays. The ZnOTCPP molecular cage exhibited
      highly selective recognition of 5,10,15,20-tetraphenylporphyrin (TPP) by optical
      and photoelectrical signals. The ZnOTCPP@TPP exhibited high emission efficiency,
      with a six-fold increase in the intensity of the emission relative to that of
      ZnOTCPP after the molecular cage ZnOTCPP captured TPP. The optical, electrical,
      and optoelectrical properties of the molecular cage ZnOTCPP could be controlled
      by tuning the interactions between the guest and the host's inorganic or organic
      moieties. Such a solid state molecular cage opens the door to controlled-delivery
      applications and provides an attractive platform for studying solid state
      supramolecular electronics and optoelectronics. 

PMID- 24042325
TI  - Diabetes: Low adiponectin levels before pregnancy linked with increased risk of
      gestational diabetes mellitus.

PMID- 24042326
TI  - Diabetes: Clinical inertia--a barrier to effective management of T2DM.

PMID- 24042324
TI  - K(ATP) channels and islet hormone secretion: new insights and controversies.
AB  - ATP-sensitive potassium channels (K(ATP) channels) link cell metabolism to
      electrical activity by controlling the cell membrane potential. They participate
      in many physiological processes but have a particularly important role in
      systemic glucose homeostasis by regulating hormone secretion from pancreatic
      islet cells. Glucose-induced closure of K(ATP) channels is crucial for insulin
      secretion. Emerging data suggest that K(ATP) channels also play a key part in
      glucagon secretion, although precisely how they do so remains controversial. This
      Review highlights the role of K(ATP) channels in insulin and glucagon secretion.
      We discuss how K(ATP) channels might contribute not only to the initiation of
      insulin release but also to the graded stimulation of insulin secretion that
      occurs with increasing glucose concentrations. The various hypotheses concerning
      the role of K(ATP) channels in glucagon release are also reviewed. Furthermore,
      we illustrate how mutations in K(ATP) channel genes can cause hyposecretion or
      hypersecretion of insulin, as in neonatal diabetes mellitus and congenital
      hyperinsulinism, and how defective metabolic regulation of the channel may
      underlie the hypoinsulinaemia and the hyperglucagonaemia that characterize type 2
      diabetes mellitus. Finally, we outline how sulphonylureas, which inhibit K(ATP)
      channels, stimulate insulin secretion in patients with neonatal diabetes mellitus
      or type 2 diabetes mellitus, and suggest their potential use to target the
      glucagon secretory defects found in diabetes mellitus.

PMID- 24042327
TI  - Cancer: Next-generation sequencing for detecting thyroid cancer.

PMID- 24042329
TI  - Cancer: Thyroid circadian clock--altered in cancer?

PMID- 24042330
TI  - Ursolic acid inhibits colorectal cancer angiogenesis through suppression of
      multiple signaling pathways.
AB  - Angiogenesis plays a critical role in the development of solid tumors by
      supplying nutrients and oxygen to support continuous growth of tumor as well as
      providing an avenue for hematogenous metastasis. Tumor angiogenesis is highly
      regulated by multiple intracellular signaling transduction cascades such as
      Hedgehog, STAT3, Akt and p70S6K pathways that are known to malfunction in many
      types of cancer including colorectal cancer (CRC). Therefore, suppression of
      tumor angiogenesis through targeting these signaling pathways has become a
      promising strategy for cancer chemotherapy. Ursolic acid (UA) is a major active
      compound present in many medicinal herbs that have long been used in China for
      the clinical treatment of various types of cancer. Although previous studies have
      demonstrated an antitumor effect for UA, the precise mechanisms of its anti
      angiogenic activity are not well understood. To further elucidate the
      mechanism(s) of the tumorcidal activity of UA, using a CRC mouse xenograft model,
      chick embryo chorioallantoic membrane (CAM) model, the human colon carcinoma cell
      line HT-29 and human umbilical vein endothelial cells (HUVECs), in the present
      study we evaluated the efficacy of UA against tumor growth and angiogenesis in
      vivo and in vitro and investigated the underlying molecular mechanisms. We found
      that administration of UA significantly inhibited tumor volume but had no effect
      on body weight changes in CRC mice, suggesting that UA can suppress colon cancer
      growth in vivo without noticeable signs of toxicity. In addition, UA treatment
      reduced intratumoral microvessel density (MVD) in CRC mice, decreased the total
      number of blood vessels in the CAM model, and dose and time-dependently inhibited
      the proliferation, migration and tube formation of HUVECs, demonstrating UA's
      antitumor angiogenesis in vivo and in vitro. Moreover, UA treatment inhibited the
      expression of critical angiogenic factors, such as VEGF-A and bFGF. Furthermore,
      UA suppressed the activation of sonic hedgehog (SHH), STAT3, Akt and p70S6K
      pathways. Collectively, our findings suggest that inhibition of tumor
      angiogenesis via suppression of multiple signaling pathways might be one of the
      mechanisms whereby UA can be effective in cancer treatment.

PMID- 24042332
TI  - Cooperation behavior between heterogeneous cations in hybrid batteries.
AB  - A cooperative behavior of Zn(2+) and Li(+) to conduct charges in a Zn-LiFePO4
      battery is disclosed. When Li(+) dissolves into the electrolyte, Zn(2+) would
      deposit, and vice versa. In light of this cooperative behavior, the battery can
      be viewed as a super hybrid system, which combines the strong points of Zn-air
      battery, lithium-ion battery and redox-flow cell. 

PMID- 24042333
TI  - Internal mammary node management in breast cancer. A review.
AB  - BACKGROUND: Internal mammary nodes visualized during sentinel node biopsy for
      breast cancer, remain an unresolved management issue. Further, both internal
      mammary node (IMN) radiotherapy and biopsy have attendant risks and hence should
      be used with caution. The purpose of this review is to highlight the available
      data and evidence. METHODS AND RESULTS: A PubMed database from 1960 to 2012 using
      key words: internal mammary nodes, breast cancer radiotherapy planning, adjuvant
      radiotherapy, sentinel node biopsy in breast cancer and selected publications on
      the significance of internal mammary nodes in breast cancer treatment, published
      data and approaches used. We found 14513 relevant papers and we selected 30 that
      clearly investigated the management of internal mammary nodes during sentinel
      node search. We focused on the incidence of IMN metastasis (6 papers), risk
      factors associated with IMN drainage (9 reports), management of IMN and the
      impact on disease free and overall patient survival (15 papers). CONCLUSIONS: The
      evidence for breast cancer axillary nodes management is good but the data for
      other draining nodes such as internal mammary nodes are far less conclusive and
      further research is needed.

PMID- 24042328
TI  - The role of estrogen and androgen receptors in bone health and disease.
AB  - Mouse models with cell-specific deletion of the estrogen receptor (ER) alpha, the
      androgen receptor (AR) or the receptor activator of nuclear factor kappaB ligand
      (RANKL), as well as cascade-selective estrogenic compounds have provided novel
      insights into the function and signalling of ERalpha and AR. The studies reveal
      that the effects of estrogens on trabecular versus cortical bone mass are
      mediated by direct effects on osteoclasts and osteoblasts, respectively. The
      protection of cortical bone mass by estrogens is mediated via ERalpha, using a
      non-nucleus-initiated mechanism. By contrast, the AR of mature osteoblasts is
      indispensable for the maintenance of trabecular bone mass in male mammals, but
      not required for the anabolic effects of androgens on cortical bone. Most
      unexpectedly, and independently of estrogens, ERalpha in osteoblast progenitors
      stimulates Wnt signalling and periosteal bone accrual in response to mechanical
      strain. RANKL expression in B lymphocytes, but not T lymphocytes, contributes to
      the loss of trabecular bone caused by estrogen deficiency. In this Review, we
      summarize this evidence and discuss its implications for understanding the
      regulation of trabecular and cortical bone mass; the integration of hormonal and
      mechanical signals; the relative importance of estrogens versus androgens in the
      male skeleton; and, finally, the pathogenesis and treatment of osteoporosis. 

PMID- 24042334
TI  - Significance of resection margin as a risk factor for local control of early
      stage breast cancer.
AB  - INTRODUCTION: Breast conserving surgery combined with sentinel node biopsy
      represents currently the gold standard of treatment for early breast cancer.
      Although breast conserving surgery has been a widely accepted method for many
      years, there remain some highly controversial unresolved issues. The present
      analysis focused on the resection margin as one of the key factors for local
      control of the disease. METHODS: Patient disease free survival and overall
      survival were collected from patients undergoing breast conserving surgery from
      2004 to 2009 at the Department of Surgery Atlas hospital Zlin, Czech Republic.
      All patients with resection margin less then 5 mm were re-resected to achieve
      this clear resection margin of 5mm or more. Disease free survival (more
      specifically local relapse free survival, metastasis free survival and regional
      free survival) and overall survival were assessed. RESULTS: The data on 330
      patients were analyzed and 286/330 cases had complete follow-up. After a median
      follow-up of 70 months, 7 patients with isolated local relapse were identified
      (2.44%), 13 patients with distant metastasis without local relapse (4.54%) and 2
      patients with relapse in the axilla without local relapse in the breast (0.7%).
      CONCLUSION: The final decision about the extent of resection margin remains
      controversial but based on the data on local control presented here it seems
      reasonable to increase the criteria for a clear resection margin to 5 mm.

PMID- 24042335
TI  - Intraparticle donor-acceptor dyads prepared using conjugated metal-ligand
      linkages.
AB  - Ruthenium nanoparticles were stabilized by the self-assembly of 1-decyne forming
      ruthenium-vinylidene interfacial bonds and further functionalized by metathesis
      reactions with 4-ethynyl-N,N-diphenylaniline (EDPA) and 9-vinylanthracene (VAN).
      Photoluminescence studies of the resulting bifunctionalized Ru(EDPA/VAN)
      nanoparticles showed that as both ligands were bound onto the nanoparticle
      surface, effective mixing of the pi electrons occurred leading to the appearance
      of excitation and emission profiles that were completely different from those of
      ruthenium nanoparticles functionalized with only EDPA or VAN. Furthermore, in
      photoelectrochemical studies, the EDPA moieties exhibited a pair of well-defined
      voltammetric peaks in the dark, which were ascribed to the redox reaction
      involving the formation of cationic radicals; however under UV photoirradiation
      the voltammetric features diminished markedly. These results strongly suggest
      that the particle-bound EDPA and VAN moieties behaved analogously to those of
      conventional molecular dyads based on the same electron-donating and -accepting
      units, where the intraparticle charge transfer was facilitated by the conjugated
      metal-ligand interfacial bonds. 

PMID- 24042336
TI  - Pediatric faculty diversity: a new landscape for academic pediatrics in the 21st
      century.

PMID- 24042337
TI  - Characterization of a canine tetranucleotide microsatellite marker located in the
      first intron of the tumor necrosis factor alpha gene.
AB  - A polymorphic tetranucleotide (GAAT)n microsatellite in the first intron of the
      canine tumor necrosis factor alpha (TNFA) gene was characterized in this study;
      139 dogs were analyzed: 22 Beagles, 26 Chihuahuas, 20 Miniature Dachshunds, 24
      Miniature Poodles, 22 Pembroke Welsh Corgis and 25 Shiba Inus. We detected the
      presence of the 4 alleles (GAAT)5, (GAAT)6, (GAAT)7 and (GAAT)8, including 9 of
      the 10 expected genotypes. The expected heterozygosity (He) and the polymorphic
      information content (PIC) value of this microsatellite locus varied from 0.389 to
      0.749 and from 0.333 to 0.682, respectively, among the 6 breeds. The allelic
      frequency differed greatly among breeds, but this microsatellite marker was
      highly polymorphic and could be a useful marker for the canine TNFA gene. 

PMID- 24042338
TI  - Taking one for the team.

PMID- 24042340
TI  - Brain acetylcholinesterase activity in shiner perch (Cymatogaster aggregata) and
      juvenile chinook salmon (Oncorhynchus tshawytscha) after application of carbaryl
      to control burrowing shrimp within Willapa Bay, Washington.
AB  - Carbaryl has been applied in Willapa Bay, Washington, for five decades to control
      burrowing shrimp (Neotrypaea californiensis and Upogebia pugettensis) on
      commercial oyster (Crassostrea gigas) beds. Concerns about effects on nontarget
      species, including fishes, have led to restrictions in use despite a lack of data
      on in situ exposure. We measured brain acetylcholinesterase (AChE) activity in
      adult Shiner perch (Cymatogaster aggregata) and juvenile Chinook salmon
      (Oncorhynchus tshawytscha) after operational applications. We hypothesized that
      exposure in Shiner perch would be greater than in juvenile Chinook salmon because
      of their greater site fidelity and benthic foraging. However, Shiner perch
      exhibited no statistically significant AChE inhibition. Enzyme activity was
      statistically decreased (<=14 %) in juvenile Chinook salmon after a second spray
      event; however, inhibition was less than that associated with overt effects and
      was similar to controls by 48 h after the spray. Diet analyses confirmed that
      Shiner perch were primarily feeding on benthic invertebrates and that juvenile
      Chinook salmon were feeding primarily within the water column. Composition of
      Shiner perch diets and amount of food consumed varied little among channels and
      time periods; however, Shiner perch on beds consumed more food 6 h after
      application than those at other time points and locations. There were no
      consistent differences in the diets of juvenile Chinook salmon within channels
      among time periods. Results suggest (1) that carbaryl applications pose little
      hazard to fish in the bay having habitat and dietary preferences similar to those
      of Shiner perch and juvenile Chinook salmon and (2) that quantification of direct
      exposure in the field is essential to adequately assess risk. 

PMID- 24042339
TI  - Rapid tuning of auditory "what" and "where" pathways by training.
AB  - Behavioral improvement within the first hour of training is commonly explained as
      procedural learning (i.e., strategy changes resulting from task familiarization).
      However, it may additionally reflect a rapid adjustment of the perceptual and/or
      attentional system in a goal-directed task. In support of this latter hypothesis,
      we show feature-specific gains in performance for groups of participants briefly
      trained to use either a spectral or spatial difference between 2 vowels presented
      simultaneously during a vowel identification task. In both groups, the
      neuromagnetic activity measured during the vowel identification task following
      training revealed source activity in auditory cortices, prefrontal, inferior
      parietal, and motor areas. More importantly, the contrast between the 2 groups
      revealed a striking double dissociation in which listeners trained on spectral or
      spatial cues showed higher source activity in ventral ("what") and dorsal
      ("where") brain areas, respectively. These feature-specific effects indicate that
      brief training can implicitly bias top-down processing to a trained acoustic cue
      and induce a rapid recalibration of the ventral and dorsal auditory streams
      during speech segregation and identification. 

PMID- 24042341
TI  - In vivo siRNA targeting of CD28 reduces UV-induced DNA damage and inflammation.

PMID- 24042342
TI  - siRNA knockdown of tissue inhibitor of metalloproteinase-1 in keloid fibroblasts
      leads to degradation of collagen type I.
AB  - Keloids are defined as overgrowths of scar tissue resulting from abnormal wound
      healing. They are characterized by excessive dermal deposition of thick,
      hyalinized collagen bundles resulting from an imbalance between the production
      and degradation of extracellular matrix (ECM) components. Matrix
      metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are
      two important regulators of ECM degradation and remodeling. To evaluate the role
      played by knockdown of TIMPs in keloid formation, we transduced human keloid
      derived fibroblasts (KFs) with small interfering RNAs targeting TIMP-1 or -2
      (siTIMP-1 or siTIMP-2) using a lentiviral vector and assessed the biological
      effects. We found that MMP-1/TIMP-1 and MMP-1/TIMP-2 complexes were suppressed
      and that MMP-2 activity was upregulated in KFs expressing siTIMP-1 or siTIMP-2.
      In addition, increased degradation of collagen type I was observed in the
      supernatant of KFs expressing siTIMP-1, but not siTIMP-2, with the suppression of
      cell viability and induction of apoptosis. These results suggest that targeting
      TIMP-1 using small interfering RNA has significant therapeutic potential as an
      approach to treating keloids through degradation of their thick collagen bundles.

PMID- 24042344
TI  - A content analysis of activity pacing in chronic pain: what are we measuring and
      why?
AB  - BACKGROUND: Activity pacing is a common intervention for patients with chronic
      pain. Over the past decade a number of instruments have been developed to measure
      this construct, but their comparative psychometric properties have not been
      examined. OBJECTIVE: To review the psychometric properties of existing measures
      of activity pacing, and provide suggestions for future research in this emerging
      area of pain research. METHODS: A narrative review of current measures of
      activity pacing followed by a discussion of the conceptual and psychometric
      challenges in this area. RESULTS: Although there is evidence supporting activity
      pacing as a unitary construct, important differences remain among the various
      measures in terms of their item content and assumptions. All existing activity
      pacing measures include items that assess activity regulation, but vary in their
      specific content. Most importantly, questionnaire items often reflect different
      purposes of pacing behaviors. DISCUSSION: Current measures of activity pacing are
      inadequate. New measures are needed that are based on specific theoretical
      models; these measures should also make the goal or intent of pacing behaviors
      explicit. Improvements in the assessment of activity pacing will likely lead to a
      better understanding of the pacing construct and the effects of pacing
      interventions.

PMID- 24042343
TI  - Complete maternal isodisomy of chromosome 5 in a Japanese patient with Netherton
      syndrome.

PMID- 24042345
TI  - Costs and utilities of manual therapy and orthopedic standard care for low
      prioritized orthopedic outpatients of working age: a cost consequence analysis.
AB  - OBJECTIVES: Treatment for musculoskeletal disorders in primary care in Sweden is
      generally initiated with advice and medication. Second-line therapy is
      physiotherapy and/or injection and radiography; third-line therapy is referral to
      an orthopedist. Manual therapy is not routine. It is a challenge to identify
      patients who benefit from treatment by different specialists. The current
      referral strategy probably contributes to long waiting lists in orthopedic
      departments, which is costly and implies prolonged suffering for the patients.
      The aim of this health economic evaluation was to compare costs and outcomes from
      naprapathic manual therapy (NMT) with orthopedic standard care for common, low
      prioritized, nonsurgical musculoskeletal disorders, after second-line treatment.
      MATERIALS AND METHODS: Diagnose Related Groups were used to define the costs, and
      the SF-36 was encoded to evaluate the outcomes in cost per quality adjusted life
      years gained. RESULTS: Results from a 12 months' follow-up showed significantly
      larger improvement for the NMT than for orthopedic standard care, significantly
      lower mean cost per patient; 5427 SEK (*Price level 2009; 1 Euro=106,213 SEK; 1
      US Dollar=76,457 SEK) (95% confidence interval, 3693-7161) compared to14298 SEK
      (95% confidence interval, 8322-20,274), and more gains in outcomes in cost per
      quality adjusted life years per patient (0.066 compared with 0.026). Thus the
      result is "dominant." DISCUSSION: It is plausible that improved outcomes and
      reasonable cost savings for low-prioritized nonsurgical outpatients would be
      attainable if NMT were available as an additional standard care option in
      orthopedic outpatient clinics.

PMID- 24042346
TI  - Transient thermal sympathectomy as a possible mechanism for hypotension after
      kyphoplasty: a case report.
AB  - BACKGROUND: Vertebroplasty and kyphoplasty are minimally invasive treatments for
      vertebral compression fractures. Although infrequent, both transitory and
      persistent adverse effects have been reported. They range from asymptomatic to
      severe neurological deficits that are caused directly by polymethylmethacrylate
      (PMMA) leakage or may be related to local or general reactions not due to PMMA
      leakage. Transitory hypotension after the procedure has been observed, but the
      characteristics and etiology of this phenomenon are not defined. OBJECTIVE: To
      describe a case of prolonged hypotension after kyphoplasty and suggest a possible
      mechanism. METHODS: Six months after L2 kyphoplasty, a 63-year-old woman with
      severe osteoporosis developed a new back pain due to compression fracture of L1
      and compression deformity of the superior L3 endplate. The patient underwent
      bilateral kyphoplasty at the L1 and L3 levels. She developed persistent
      hypotension for approximately 46 hours immediately after the procedure. Common
      causes of hypotension were ruled out and the event resolved spontaneously.
      RESULTS: On the basis of needle placement, the temporal relationship between the
      procedure and blood pressure change, and the lack of other identifiable causes,
      thermal sympathectomy from heating of the PMMA adjacent to the paravertebral
      sympathetic chain is proposed as a potential mechanism. LIMITATIONS: Single case
      report based on clinical observation. DISCUSSION: Prolonged hypotension can
      complicate kyphoplasty at upper lumbar levels. Two days of severe hypotension has
      not been described as a complication of kyphoplasty. Although the mechanism is
      unknown, a transient thermal sympathectomy may be the cause.

PMID- 24042347
TI  - Investigation of central pain processing in postoperative shoulder pain and
      disability.
AB  - BACKGROUND: Measures of central pain processing like conditioned pain modulation
      and suprathreshold heat pain response (SHPR) have been described to assess
      different components of central pain modulatory mechanisms. Central pain
      processing potentially plays a role in the development of postsurgical pain,
      however, the role of conditioned pain modulation and SHPR in explaining
      postoperative clinical pain and disability is still unclear. METHODS: Seventy
      eight patients with clinical shoulder pain were included in this study. Patients
      were examined before shoulder surgery, at 3 months, and 6 months after surgery.
      The primary outcome measures were pain intensity and upper extremity disability.
      RESULTS: Analyses revealed that the change score (baseline- 3 mo) of fifth pain
      rating of SHPR accounted for a significant amount of variance in 6-month
      postsurgical clinical pain intensity and disability after age, sex, preoperative
      pain intensity, and relevant psychological factors were considered. CONCLUSIONS:
      The present study suggests that baseline measures of central pain processing were
      not predictive of 6-month postoperative pain outcome. Instead, the 3-month change
      in SHPR might be a relevant factor in the transition to an elevated 6-month
      postoperative pain and disability outcomes. In patients with shoulder pain, the 3
      month change in a measure of central pain processing might be a relevant factor
      in the transition to elevated 6-month postoperative pain and disability scores.

PMID- 24042348
TI  - Parental distress and catastrophic thoughts about child pain: implications for
      parental protective behavior in the context of child leukemia-related medical
      procedures.
AB  - OBJECTIVES: Treatment for childhood leukemia requires frequent lumbar punctures
      (LP) and bone marrow aspirations (BMA), often described by children and parents
      as more distressing than the disease itself. Findings in schoolchildren and
      chronic pain samples indicate that increased parental distress may increase
      parental protective, pain-attending behavior, which is associated with more child
      pain and distress. However, in the context of invasive medical procedures, it is
      unknown which parents are likely to become most distressed and engage in pain
      attending behavior, and how this impacts the children's experiences. The present
      study investigated the impact of parental catastrophic thoughts upon parental
      distress and pain-attending behavior (verbal and nonverbal). Furthermore, the
      association between parental responses and the children's pain behavior, pain,
      and distress was examined. MATERIALS AND METHODS: A total of 46 parents of
      children with leukemia (range, 0.6 to 15 y) who underwent a LP/BMA procedure
      participated in this study. Parental catastrophizing was assessed before and
      parental and child distress was assessed after the LP/BMA procedure. Parental
      pain-attending behavior and the child's pain behavior were observed before and
      after the LP/BMA procedure. RESULTS: Findings indicated that heightened parental
      catastrophic thinking contributed to increased parental distress during LP/BMA
      and less pain-attending behavior before the LP/BMA procedure, especially in young
      children. In contrast, heightened distress in parents with high levels of
      catastrophizing contributed to increased engagement in postprocedural pain
      attending behavior. For young children, increased preprocedural pain-attending
      behavior was related to more child distress, pain, and pain behavior. DISCUSSION:
      The findings demonstrate the importance of parental catastrophic thinking in
      understanding their caregiving responses and preparing parents and children for
      painful invasive medical procedures.

PMID- 24042349
TI  - Associations between psychosocial factors and pain intensity, physical
      functioning, and psychological functioning in patients with chronic pain: a cross
      cultural comparison.
AB  - OBJECTIVE: Current models of chronic pain recognize that psychosocial factors
      influence pain and the effects of pain on daily life. The role of such factors
      has been widely studied on English-speaking individuals with chronic pain. It is
      possible that the associations between such factors and adjustment may be
      influenced by culture. This study sought to evaluate the importance of coping
      responses, self-efficacy beliefs, and social support to adjust to chronic pain in
      a sample of Portuguese patients, and discuss the findings with respect to their
      similarities and differences from findings of studies on English-speaking
      individuals. MATERIALS AND METHODS: Measures of pain intensity and interference,
      physical and psychological functioning, coping responses, self-efficacy, and
      satisfaction with social support were administered to a sample of 324 Portuguese
      patients with chronic musculoskeletal pain. Univariate and multivariate analyses
      were computed. Findings were interpreted with respect to those from similar
      studies using English-speaking individuals. RESULTS: Coping responses and
      perceived social support were significantly associated with pain interference and
      both physical and psychological functioning; self-efficacy beliefs were
      significantly associated with all criterion variables. All coping responses,
      except for task persistence, were positively associated with pain interference
      and negatively associated with physical and psychological functioning, with the
      strongest associations found for catastrophizing, praying/hoping, guarding,
      resting, asking for assistance, and relaxation. DISCUSSION: The findings provide
      support for the importance of the psychosocial factors studied in terms of
      adjustment to chronic pain in Portuguese patients, and also suggest the
      possibility of some differences in the role of these factors due to culture.

PMID- 24042350
TI  - Self-regulation (recovery) from pain: association between time-based measures of
      infant pain behavior and prenatal exposure to maternal depression and anxiety.
AB  - OBJECTIVES: Capacities for self-regulation that influence infant adaptation to
      noxious stimulation require investigation of changes in behavior over time.
      Prenatal exposure to maternal depression and anxiety (MDA) has been linked to
      altered infant pain reactivity; however, findings are inconclusive about MDA
      dynamic impacts on recovery. This study quantified the temporal profile of
      behavioral response and recovery to routine heel lance (HL) of infants with and
      without prenatal-MDA exposure. Aims were to examine whether MDA were associated
      with alterations in time-based measures of infant behavior and sequential
      patterning in pain expression. MATERIALS AND METHODS: Videotaped facial, body,
      and cry behaviors of 21 full-term newborns were coded second-by-second for the
      duration of HL (baseline, HL, Post-HL) using validated behavioral coding systems.
      Mean heart rate and proportion of time infants spent exhibiting behavioral
      measures were compared between infant groups and over subphases of HL. Simple
      regressions, latency, and Yule-Q measures of effect size examined which behaviors
      were predicted by prenatal-MDA and magnitude of sequential association between
      first and subsequent behavior. RESULTS: During HL, all infants reacted
      immediately and substantially on heart rate, facial, body, and cry measures.
      Facial reactivity was followed within 2 seconds by body and cry behavior. There
      were no group differences in magnitude of initial behavioral reactions, but
      during Post-HL, MDA-exposed infants spent more time crying in a weak/exhausted
      manner and displayed strained and erratic limb movement and immobility.
      CONCLUSIONS: Temporal measures can further help in understanding of infant
      complex behavioral responses to pain. Delayed recovery in MDA-exposed infants
      suggested diminished capacities for self-regulation of noxious distress.

PMID- 24042351
TI  - Nonmedical use of tapentadol immediate release by college students.
AB  - OBJECTIVES: Prescription opioid analgesics play an important role in managing
      moderate to severe pain. An unintended consequence of the availability of these
      drugs is nonmedical use. We report rates and methods of nonmedical use of the
      analgesic tapentadol immediate release (IR) and other commonly prescribed opioid
      analgesics among US college students following the launch of tapentadol IR in
      June 2009. MATERIALS AND METHODS: The Researched Abuse, Diversion and Addiction
      Related Surveillance System College Survey Program collects data from
      approximately 2000 self-identified college students throughout the United States
      during fall, spring, and summer terms using a web-based questionnaire. Responses
      from July 2009 through September 2011 were analyzed for the rate of nonmedical
      use of tapentadol IR. RESULTS: Nonmedical use of prescription opioids was
      reported by 1626 of 13,514 respondents (12.0%); tapentadol IR use was reported by
      101 respondents (0.7%). The rate of nonmedical tapentadol IR use per 100,000
      population was highest in 4Q2009 (0.013 per 100,000 population) and decreased
      over the subsequent 2 years to 0.004 per 100,000 population. Similarly, the rate
      per 1000 unique recipients of dispensed drug (URDD) was highest in 4Q2009 (0.66
      per 1000 URDD) and decreased to 0.06 per 1000 URDD. The primary route of
      administration endorsed for nonmedical tapentadol IR use was intact swallow
      (49.5%), chewed and swallowed (41.6%), followed by inhalation (20.8). DISCUSSION:
      Since its launch, rates of nonmedical tapentadol IR use by college students have
      been low and have decreased over time. The initial levels of reported nonmedical
      use may represent a brief period of experimentation after introduction.

PMID- 24042352
TI  - Oxidative stress induces proliferation of colorectal cancer cells by inhibiting
      RUNX3 and activating the Akt signaling pathway.
AB  - We recently reported that the tumor suppressor Runt-related transcription factor
      3 (RUNX3) is silenced in colorectal cancer cells via oxidative stress-induced
      hypermethylation of its promoter. The resulting downregulation of RUNX3
      expression influences cell proliferation. Activation of the Akt signaling pathway
      is also associated with cell survival and proliferation; however, the effects of
      oxidative stress on the relationship between RUNX3 and Akt signaling are largely
      unknown. Therefore, this study investigated the mechanisms involved in cell
      proliferation caused by oxidative stress-induced silencing of RUNX3. The levels
      of RUNX3 mRNA and protein were downregulated in response to treatment of the
      human colorectal cancer cell line SNU-407 with H2O2. Treatment of the cells with
      H2O2 also upregulated Akt mRNA and protein expression, and inhibited the binding
      of RUNX3 to the Akt promoter. The inverse correlation between the expression
      levels of RUNX3 and Akt in H2O2-treated cells was also associated with nuclear
      translocation of beta-catenin and upregulation of cyclin D1 expression, which
      induced cell proliferation. H2O2 treatment also increased the binding of beta
      catenin to the cyclin D1 promoter. The results presented here demonstrate that
      reactive oxygen species silence the tumor suppressor RUNX3, enhance the Akt
      mediated signaling pathway, and promote the proliferation of colorectal cancer
      cells. 

PMID- 24042353
TI  - Championing truly collaborative team-based care.

PMID- 24042355
TI  - A Pt-nanoparticle electrocatalytic assay used for PCR-free sensitive telomerase
      detection.
AB  - An electrocatalytic assay was developed for telomerase activity detection by
      using superior catalytic properties of Pt nanoparticles. This design was PCR
      free, and highly sensitive for telomerase with a detection limit of less than 2
      cells. 

PMID- 24042357
TI  - Guiding patients to safe weight loss.
AB  - Many patients have questions about diets, and those adhering to specific diets
      need patient-tailored monitoring. Nurse practitioners are often called upon to
      advise, prescribe, and monitor specific weight-reduction and weight-control
      diets. This article provides guidelines for safe weight reduction and a review of
      some popular diets.

PMID- 24042356
TI  - [Reverse takotsubo cardiomyopathy-a life-threatening disease. Successful
      resuscitation of a 31-year-old woman with cardiologic shock after a visit to the
      dentist].
AB  - We report on a 31-year-old woman requiring resuscitation because of ventricular
      fibrillation during a standard dental procedure with local anaesthesia. In
      cardiac ventriculography, reverse takotsubo cardiomyopathy was diagnosed. Because
      of protracted cardiogenic shock early treatment with calcium sensitizers, as well
      as the use of an intra-aortic ballon pump (IABP) were necessary to achieve stable
      hemodynamics. Despite a maximum neuron-specific enolase value of 37.8 ng/ml, the
      patient was released from the hospital 19 days after admission without a
      neurological deficit and with completely restored cardiac function.

PMID- 24042358
TI  - Stepping up to be an expert witness.

PMID- 24042360
TI  - Acute bronchitis: Evaluation and management.
AB  - Acute bronchitis affects millions of individuals, significantly impacting patient
      health and the healthcare industry. Understanding evaluation and treatment
      guidelines for acute bronchitis allows the nurse practitioner to practice
      comprehensive care for patients. This article reviews evidence-based practices
      when caring for the patient with acute bronchitis, promoting optimization of
      healthy outcomes.

PMID- 24042364
TI  - First principles prediction of an insensitive high energy density material.
AB  - A new high performance yet insensitive explosive is proposed, based on an
      extensive computational study of tris(tetrazolyl)amine in the solid state and in
      the gas phase. The calculations for the solid state employ the PBE density
      functional with empirical dispersion correction while the gas phase calculations
      use the higher level of B3LYP and MP2. Two stable crystalline structures of
      tris(tertrazolyl)amine were located belonging to P1 and P21 space groups. The
      crystal structures obtained reveal that solid tris(tertrazolyl)amine is organized
      in layers with a very small interlayer spacing, due to pi stacking, as well as
      significant inter and intra-molecular hydrogen bonding. Application of these
      results to the calculation of the detonation velocity and pressure indicate high
      performance for both phases, especially the P21 phase. At the same time the small
      value found for the interlayer spacing and the significant hydrogen bonding
      suggest relatively high stability. These results point to a promising new
      explosive material with a balance between high performance and insensitivity. 

PMID- 24042365
TI  - Perceptions, knowledge, and satisfaction with contralateral prophylactic
      mastectomy among young women with breast cancer: a cross-sectional survey.
AB  - Chinese translation BACKGROUND: Rates of contralateral prophylactic mastectomy
      (CPM) have increased dramatically, particularly among younger women with breast
      cancer, but little is known about how women approach the decision to have CPM.
      OBJECTIVE: To examine preferences, knowledge, decision making, and experiences of
      young women with breast cancer who choose CPM. DESIGN: Cross-sectional survey.
      SETTING: 8 academic and community medical centers that enrolled 550 women
      diagnosed with breast cancer at age 40 years or younger between November 2006 and
      November 2010. PATIENTS: 123 women without known bilateral breast cancer who
      reported having bilateral mastectomy. MEASUREMENTS: A 1-time, 23-item survey that
      included items related to decision making, knowledge, risk perception, and breast
      cancer worry. RESULTS: Most women indicated that desires to decrease their risk
      for contralateral breast cancer (98%) and improve survival (94%) were extremely
      or very important factors in their decision to have CPM. However, only 18%
      indicated that women with breast cancer who undergo CPM live longer than those
      who do not. BRCA1 or BRCA2 mutation carriers more accurately perceived their risk
      for contralateral breast cancer, whereas women without a known mutation
      substantially overestimated this risk. LIMITATIONS: The survey, which was
      administered a median of 2 years after surgery, was not validated, and some
      questions might have been misinterpreted by respondents or subject to recall
      bias. Generalizability of the findings might be limited. CONCLUSION: Despite
      knowing that CPM does not clearly improve survival, women who have the procedure
      do so, in part, to extend their lives. Many women overestimate their actual risk
      for cancer in the unaffected breast. Interventions aimed at improving risk
      communication in an effort to promote evidence-based decision making are
      warranted. PRIMARY FUNDING SOURCE: Susan G. Komen for the Cure.

PMID- 24042366
TI  - Cost-effectiveness of tolvaptan in autosomal dominant polycystic kidney disease.
AB  - Chinese translation BACKGROUND: In the TEMPO (Tolvaptan Efficacy and Safety in
      Management of Autosomal Dominant Polycystic Kidney Disease and Its Outcomes)
      trial, tolvaptan significantly reduced expansion of kidney volume and loss of
      kidney function. OBJECTIVE: To determine how the benefits of tolvaptan seen in
      TEMPO may relate to longer-term health outcomes, such as progression to end-stage
      renal disease (ESRD) and death, and cost-effectiveness. DESIGN: A decision
      analytic model. DATA SOURCES: Published literature from 1993 to 2012. TARGET
      POPULATION: Persons with early autosomal dominant polycystic kidney disease. TIME
      HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Patients received
      tolvaptan therapy until death, development of ESRD, or liver complications or no
      tolvaptan therapy. OUTCOME MEASURES: Median age at ESRD onset, life expectancy,
      discounted quality-adjusted life-years and lifetime costs (in 2010 U.S. dollars),
      and incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS:
      Tolvaptan prolonged the median age at ESRD onset by 6.5 years and increased life
      expectancy by 2.6 years. At $5760 per month, tolvaptan cost $744 100 per quality
      adjusted life-year gained compared with standard care. RESULTS OF SENSITIVITY
      ANALYSIS: For patients with autosomal dominant polycystic kidney disease that
      progressed more slowly, the cost per quality-adjusted life-year gained was even
      greater for tolvaptan. LIMITATION: Although TEMPO followed patients for 3 years,
      the main analysis assumed that clinical benefits persisted over patients'
      lifetimes. CONCLUSION: Assuming that the benefits of tolvaptan persist in the
      longer term, the drug may slow progression to ESRD and reduce mortality rates.
      However, barring an approximately 95% reduction in price, cost-effectiveness does
      not compare favorably with many other commonly accepted medical interventions.
      PRIMARY FUNDING SOURCE: National Institutes of Health and Agency for Healthcare
      Research and Quality.

PMID- 24042367
TI  - Effects of varenicline on smoking cessation in adults with stably treated current
      or past major depression: a randomized trial.
AB  - Chinese translation BACKGROUND: Depression is overrepresented in smokers.
      OBJECTIVE: To evaluate smoking abstinence and changes in mood and anxiety levels
      in smokers with depression treated with varenicline versus placebo. DESIGN: Phase
      4, multicenter, parallel, 1:1 allocation, double-blind, randomization trial.
      Randomization, stratified by antidepressant use and depression score at baseline,
      was blocked in sizes of 4. (ClinicalTrials.gov: NCT01078298). SETTING: 38 centers
      in 8 countries. PARTICIPANTS: 525 adult smokers with stably treated current or
      past major depression and no recent cardiovascular events. INTERVENTION:
      Varenicline, 1 mg twice daily, or placebo for 12 weeks, with 40-week nontreatment
      follow-up. MEASUREMENTS: Primary outcome was carbon monoxide-confirmed continuous
      abstinence rate (CAR) for weeks 9 to 12. Other outcomes included CARs assessed
      during nontreatment follow-up and ratings of mood, anxiety, and suicidal ideation
      or behavior. RESULTS: 68.4% versus 66.5% of the varenicline and placebo groups,
      respectively, completed the study. Varenicline-treated participants had higher
      CARs versus placebo at weeks 9 to 12 (35.9% vs. 15.6%; odds ratio [OR], 3.35 [95%
      CI, 2.16 to 5.21]; P < 0.001), 9 to 24 (25.0% vs. 12.3%; OR, 2.53 [CI, 1.56 to
      4.10]; P < 0.001), and 9 to 52 (20.3% vs. 10.4%; OR, 2.36 [CI, 1.40 to 3.98]; P =
      0.001). There were no clinically relevant differences between groups in suicidal
      ideation or behavior and no overall worsening of depression or anxiety in either
      group. The most frequent adverse event was nausea (varenicline, 27.0%; placebo,
      10.4%). Two varenicline-group participants died during the nontreatment phase.
      LIMITATIONS: Some data were missing, and power to detect differences between
      groups was low in rare events. Smokers with untreated depression, with co
      occurring psychiatric conditions, or receiving mood stabilizers and
      antipsychotics were not included. CONCLUSION: Varenicline increased smoking
      cessation in smokers with stably treated current or past depression without
      exacerbating depression or anxiety. PRIMARY FUNDING SOURCE: Pfizer.

PMID- 24042368
TI  - Determining the noninfectious complications of indwelling urethral catheters: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Although the epidemiology of catheter-associated urinary tract
      infection is well-described, little is known about noninfectious complications
      resulting from urethral catheter use. PURPOSE: To determine the frequency of
      noninfectious complications after catheterization. DATA SOURCES: MEDLINE, EMBASE,
      Cochrane Central Register of Controlled Trials, CINAHL, Conference Papers Index,
      BIOSIS Previews, Scopus, and ClinicalTrials.gov were searched for human studies
      without any language limits and through 30 July 2012. STUDY SELECTION: Clinical
      trials and observational studies assessing noninfectious complications of
      indwelling urethral catheters in adults. DATA EXTRACTION: Relevant studies were
      sorted into 3 categories: short-term catheterization in patients without spinal
      cord injury (SCI), long-term catheterization in patients without SCI, and
      catheterization in patients with SCI. The proportion of patients who had bladder
      cancer, bladder stones, blockage, false passage, gross hematuria, accidental
      removal, urine leakage, or urethral stricture was then pooled using random
      effects models. DATA SYNTHESIS: Thirty-seven studies (2868 patients) were pooled.
      Minor complications were common. For example, the pooled frequency of urine
      leakage ranged from 10.6% (95% CI, 2.4% to 17.7%) in short-term catheterization
      cohorts to 52.1% (CI, 28.6% to 69.5%) among outpatients with long-term indwelling
      catheters. Serious complications were also noted, including urethral strictures,
      which occurred in 3.4% (CI, 1.0% to 7.0%) of patients with short-term
      catheterization. For patients with SCI, 13.5% (CI, 3.4% to 21.9%) had gross
      hematuria and 1.0% (CI, 0.0% to 5.0%) developed bladder cancer. LIMITATIONS:
      Although heterogeneity existed across studies for several outcomes, most could be
      accounted for by differences between studies with respect to quality and sex
      composition. Evidence published after 30 July 2012 is not included. CONCLUSION:
      Many noninfectious catheter-associated complications are at least as common as
      clinically significant urinary tract infections. PRIMARY FUNDING SOURCE: Agency
      for Healthcare Research and Quality.

PMID- 24042369
TI  - Acute HIV-1 infection: a call to action.

PMID- 24042370
TI  - Contralateral prophylactic mastectomy: perceptions versus reality.

PMID- 24042371
TI  - Translating science to improve health: hope for patients with kidney disease at
      what cost?

PMID- 24042372
TI  - The evening seminar.

PMID- 24042373
TI  - The man who worked too hard.

PMID- 24042375
TI  - Comparative effectiveness of multivessel coronary artery bypass graft surgery and
      multivessel percutaneous coronary intervention.

PMID- 24042376
TI  - Comparative effectiveness of multivessel coronary artery bypass graft surgery and
      multivessel percutaneous coronary intervention.

PMID- 24042377
TI  - Prostate cancer treatment choices.

PMID- 24042378
TI  - Prostate cancer treatment choices.

PMID- 24042379
TI  - Summaries for patients. Do women with breast cancer overestimate their risk for
      cancer in the unaffected breast?

PMID- 24042380
TI  - Summaries for patients. Does varenicline help people with depression quit
      smoking?

PMID- 24042381
TI  - Review: levonorgestrel IU system, OCPs, and antifibrinolytics each reduce
      bleeding in endometrial dysfunction.

PMID- 24042382
TI  - Early surgery and initial conservative therapy did not differ for outcomes in
      lobar intracerebral hematomas.

PMID- 24042383
TI  - Aspirin after dalteparin was noninferior to continued dalteparin for preventing
      VTE after total hip arthroplasty.

PMID- 24042384
TI  - Review: rivaroxaban causes less fatal bleeding, but does not reduce mortality,
      compared with VKAs.

PMID- 24042385
TI  - Prone positioning for 16 h/d reduced mortality more than supine positioning in
      early severe ARDS.

PMID- 24042386
TI  - Tranexamic acid reduced mortality in trauma patients who were bleeding or at risk
      for bleeding.

PMID- 24042387
TI  - Universal decolonization was better than MRSA screening and isolation for
      preventing nosocomial ICU infections.

PMID- 24042388
TI  - 5 days of prednisone was noninferior to 14 days in patients with acute COPD
      exacerbation.

PMID- 24042389
TI  - A high- or low-dose triamcinolone injection improved pain and function in
      adhesive capsulitis.

PMID- 24042390
TI  - Insulin pumps with a sensor and threshold-suspend reduced nocturnal hypoglycemia
      in type 1 diabetes.

PMID- 24042391
TI  - Prophylactic tenofovir reduced HIV infection in injectable drug users.

PMID- 24042392
TI  - Meta-analysis: selective estrogen-receptor modulators reduce breast cancer
      incidence.

PMID- 24042393
TI  - Mortality among Japanese with a history of Kawasaki disease: results at the end
      of 2009.
AB  - BACKGROUND: The long-term outcomes of Kawasaki disease (KD) are unknown. METHODS:
      Fifty-two collaborating hospitals collected data on all patients who had received
      a new definite diagnosis of KD between July 1982 and December 1992. Patients were
      followed until December 31, 2009 or death. Standardized mortality ratios (SMRs)
      were calculated based on Japanese vital statistics data. RESULTS: Of the 6576
      patients enrolled, 46 (35 males and 11 females) died (SMR: 1.00; 95% CI: 0.73
      1.34). Among persons without cardiac sequelae, SMRs were not high after the acute
      phase of KD (SMR: 0.65; 95% CI: 0.41-0.96). Among persons with cardiac sequelae,
      13 males and 1 female died during the observation period (SMR: 1.86; 95% CI: 1.02
      3.13). CONCLUSIONS: In this cohort, the mortality rate among Japanese with
      cardiac sequelae due to KD was significantly higher than that of the general
      population. In contrast, the rates for males and females without sequelae were
      not elevated.

PMID- 24042394
TI  - [The cerebral perivascular spaces: review of the literature on diffuse or focal
      expansion].
AB  - Virchow-Robin spaces (VRS) are pial-lined, interstitial fluid-filled structures
      that do not directly communicate with the subarachnoid space, accompany
      penetrating arteries and veins and can be visualized on magnetic resonance
      imaging. This article reviews the imageology characteristics, the functions, the
      causes and the relation with neurological disorders of VRS. 

PMID- 24042395
TI  - [Diagnostic tools in neurodegenerative disorders of adult-elderly].
AB  - Neurodegenerative disorders are an inhomogeneous group of neurological diseases
      that affect a large part of the population because of the rise in life
      expectancy. Although clinical manifestations are important to make the correct
      diagnosis, the new advanced imaging technique represent a very useful tool for
      the diagnostic work-up. 

PMID- 24042396
TI  - [Acustic neurinoma: correlation between clinic and MRI].
AB  - The purpose of this paper is to study acoustic neuroma diagnostic process,
      describe tumor's molecular basis and its magnetic resonance imaging
      characterization, which is considered to be the gold standard diagnostic tool to
      study this disease. 

PMID- 24042397
TI  - [New development in neuroradiological diagnosis of migraine].
AB  - Migraine is one of the most common forms of primary headache. In recent years
      there have been important discoveries thanks to a greater understanding of
      conventional radiologic studies and the advent of the advanced exams. This has
      led to a revolution of the knowledge of its pathophysiological mechanisms and
      opens the way for future therapeutic developments. 

PMID- 24042398
TI  - [From anatomy to image: the cranial nerves at MRI].
AB  - In this article, we review the expected course of each of the 12 cranial nerves.
      Traditional magnetic resonance imaging depicts only the larger cranial nerves but
      SSFP sequences of magnetic resonance imaging are capable of depicting the
      cisternal segments of 12 cranial nerves and also provide submillimetric spatial
      resolution. 

PMID- 24042399
TI  - [The value of the MRI in defining the morfology of cerebral aging].
AB  - White matter changes are one of the several aging brain alterations. Actually,
      magnetic resonance imaging is the best diagnostic tool in investigation and
      monitoring these lesions that determine some common clinical manifestations in
      the elderly population. 

PMID- 24042400
TI  - [Enlargment of Virchow-Robin spaces in cranial trauma: literature review].
AB  - In this review it is discussed the role of mild traumatic brain injury as a cause
      of Virchow-Robin spaces (VRS) pathological enlargement. Anatomy and physiology of
      normal VRS, and their immunological role are described. Special attention is
      given to magnetic resonance imaging findings of both normal and enlarged
      perivascular spaces. 

PMID- 24042401
TI  - [Chordoma: diagnostic considerations and review of the literature].
AB  - Chordoma is a rare malignant tumor of the bone; it arises from embryonic remnants
      of the primitive notochord and occurs along the midline from the skull base to
      the sacrum. In this article, we reviewed the origin, location, clinical,
      histopatological and imaging features, treatment, and differential diagnosis of
      chordoma. 

PMID- 24042402
TI  - [18F-FDG PET/CT in staging and restaging cholangiocarcinoma].
AB  - The prognosis for hepatobiliary malignancies is dismal. Surgery remains the
      primary curative option. The positron emission tomography/computed tomography
      (PET/CT) provides simultaneous metabolic and anatomic information on tumors in
      the same imaging session. The role of PET/CT in detecting hepatobiliary
      malignancies has not yet been established. The purpose of this review was to
      examine the literature on the use of PET/CT in cholangiocarcinomas, also in order
      to improve the preoperative staging and the restaging, for a proper oncology
      management of patients. 

PMID- 24042403
TI  - [Imaging and radioguided surgery of tumors NETs].
AB  - Neuroendocrine tumors tend to grow slowly and are notoriously difficult to
      localize, at least in the early stages. Metastases are in most cases already
      present at the time of diagnosis. Somatostatin receptor scintigraphy improves
      detection of small and occult NET tumors. Intraoperative probe counting with a
      hand-held gamma probe can identify tumors even when they are small and
      impalpable, but receptor positive. This advanced operative approach may improve
      the survival of these patients. 

PMID- 24042404
TI  - [Radionuclide imaging of neurendocrine tumors: biological basis and diagnostic
      results].
AB  - Many radiopharmaceuticals have been successfully used in nuclear medicine to
      detect neuroendocrine tumors, and many of them are based on a specific mechanism
      of uptake, while others are non-specific probes. This "review" focuses on the
      clinical applications of metaiodobenzylguanidine, (111)In-pentreotide and
      positron emission tomography (PET) tracers. New avances in diagnostic imaging
      will be discussed. Molecular imaging serves these diagnostic functions and
      provides powerful means for non-invasively detecting disease.

PMID- 24042405
TI  - [Virtual colonoscopy and PET/CT for diagnosis and staging of colorectal cancer].
AB  - Colo-rectal cancer is the most common malignancy of the gastrointestinal tract
      and is the third frequency for malignancy in humans. CT and MRI development
      allows an early diagnosis and a modulation of the therapeutic approach. Many
      papers seem to confirm the role of PET/CT and virtual colonography in the
      evaluation of primary lesions. The PET/CT appears mode accurate in assessing
      lymph node metastases. Today, new approaches such as virtual colonoscopy and
      PET/CT open new horizons in the diagnosis and staging of cancer of the colon and
      rectum. 

PMID- 24042406
TI  - [Effectiveness of conventional diagnostic radiology and nuclear medicine in the
      treatment of pain from bone metastases].
AB  - Bone is one of the most common metastasis sites from solid tumors. Bone pain due
      to metastatic neoplastic growth is due to tumor infiltration and expansion of
      bone membranes. Treatment of acute and chronic pain represents one of the
      greatest problems in clinical oncology, requiring a multidisciplinary approach.
      This review focuses on the effectiveness of conventional diagnostic radiology and
      nuclear medicine for the detection, management and treatment of pain from bone
      metastasis. 

PMID- 24042407
TI  - [Cardiac sympathetic innervation imaging with myocardial MIBG scintigraphy].
AB  - Metaiodobenzylguanidine (MIBG) was developed initially as a tracer for
      oncological imaging; when labeled with 123 I or 131 I, it may detect APUDomas,
      such as pheochromocytomas and paragangliomas. In the last years, MIBG has found
      an important role also in neurology and cardiology, as cardiac innervation
      tracer. Actually, MIBG cardiac imaging is a universally accepted method to
      estimate cardiac sympathetic innervations. This review covers the role of MIBG
      cardiac imaging in Parkinson disease and parkinsonisms, from the
      pathophysiological premises for cardiac denervation to new emerging data. 

PMID- 24042408
TI  - [Choice of the imaging technique for the diagnosis of bone metastases].
AB  - Bone is the third common site of distant metastases in cancer patients. Bone
      metastases may have implications for prognosis, quality of life, and local and
      systemic therapy. Numerous imaging modalities may be used to detect bone
      metastases. The two main anatomical modalities are computed tomography (CT) and
      magnetic resonance imaging (MRI), with many variants proposed for the MRI
      procedure, including diffusion-weighted imaging. The two main functional
      modalities are scintigraphy and PET/CT, also with many variants in the
      radiopharmaceuticals. Aim of our paper is to review the most important radio
      compounds that can be successfully used to detect and/or characterize bone
      metastases. 

PMID- 24042409
TI  - [Cytological diagnosis of lymph nodes by instrumental guide: ultrasonography and
      CT].
AB  - Imaging techniques, such as ultrasound imaging, computed tomography, positron
      emission tomography or magnetic resonance imaging, are highly accurate procedures
      for the detection of lymph node enlargement, but none of them has the same
      sensitivity in the biological definition and in the cause of enlargement.
      Therefore, a direct evaluation of corresponding lymph nodes is necessary in most
      cases and fine needle cytology (FNC) is one of the most frequently used
      techniques for this purpose. The same imaging procedures are often used to
      perform targeted biopsies including FNC. This study discusses procedures,
      indications, advantages and limitations of imaging techniques as a support to
      FNC. 

PMID- 24042410
TI  - [Pulmonary arteriovenous fistulas in patients with hereditary hemorrhagic
      telangiectasia: role of MR angiography].
AB  - The aim of this work is to establish the accuracy of pulmonary magnetic resonance
      angiography (MRA) compared to multidetector computed tomography (MDCT) and
      pulmonary angiography in the diagnostic evaluation of pulmonary arteriovenous
      malformations (PAVMs) in patients with hereditary hemorrhagic telangiectasia.
      Eight consecutive patients underwent MRA, MDCT and pulmonary angiography. All
      patients were carriers of PAVMs amenable to endovascular treatment. The
      parameters we have evaluated were the presence, the number of fistulas and the
      diameter of the feeding artery of the malformation. In all cases, the findings of
      the three tests were comparable. In only one case, MR images were considered
      qualitatively poorer than MDCT, although sufficient for the recognition of the
      lesion located in the hilum. The diameters of the arteries showed no
      statistically differences between MRA and CT. In conclusion, the MRA technique
      was found to be valid and reliable in the diagnosis of PAVMs in patients with
      HHT. 

PMID- 24042412
TI  - [Chronic pancreatitis: which is the role of 320-row CT for the staging?].
AB  - The purpose of this study was to evaluate the diagnostic potential of multi
      planar and volumetric reconstructions obtained from isotropic data by using 16
      slice computed tomography (CT) in the diagnosis and staging of chronic
      pancreatitis. In a group of 42 patients CT images were evaluated searching for
      alterations in morphology and structure of the pancreas, alterations of the
      Wirsung duct, dilatation of the bile ducts, fluid collections, and vascular
      involvement of the digestive tract. The disease was then staged in mild, moderate
      and severe and correlated with the clinical staging. CT allowed the recognition
      of chronic pancreatitis in all cases. The staging was correct in 25/42 patients,
      with an accuracy rate of 59.5%. In the staging of moderate and severe forms, CT
      correlation with clinical and laboratory data was valid, but in mild forms it
      appeared less significant. Multi-detector CT is accurate in the recognition of
      moderate, advanced forms of chronic pancreatitis and in the identification of its
      complications, while it is poorly correlated with the clinical staging in mild
      forms of the disease. 

PMID- 24042411
TI  - [Adult transient intestinal intussusception: can abdominal CT guide resolution?].
AB  - The purpose of this study was to evaluate the adult transient intestinal
      intussusceptions on CT before and after the administration of gastrointestinal
      contrast material. We evaluated two different gastrointestinal contrast
      materials: hyperdense and hypodense. In all cases the gastrointestinal contrast
      agent solved the invaginations. In the group of patients treated with hypodense
      contrast medium relapses occurred in the short and long term; no recurrence was
      observed in the other group. CT is useful in the recognition of intestinal
      intussusception. The gastrointestinal contrast agent could define the real
      transience of intussusceptions and hyperdense contrast agent could be more
      effective in short and long term resolution. 

PMID- 24042413
TI  - [Unusual sentinel lymph nodes detected by lymphoscintigraphy in cutaneous
      melanoma patients].
AB  - Lymphoscintigraphy and radio-guided research of the sentinel lymph node is the
      most important investigation in the staging of patients with cutaneous melanoma,
      because it allows the identification of the lymphatic drainage pathways, not
      always predictable, and locate the sentinel node in classic basins and in
      "unexpected" regions. The aim of this study was to evaluate the incidence of
      cases of unusual sentinel nodes detected by lymphoscintigraphy and their
      prognostic significance in patients with cutaneous melanoma. 

PMID- 24042414
TI  - [Correlation between cognitive impairment and plasma levels of clusterin/ApoJ in
      Parkinson disease patients not affected by dementia].
AB  - Cognitive impairment is frequent in patients with Parkinson's disease (PD), and
      can range from mild deterioration to dementia. Recently a contribution of
      Alzheimer's disease for the cognitive dysfunction in PD has been proposed,
      whereas the presence of tau protein and amyloid was recognized. Clusterin/ApoJ is
      a protein involved in the deposition of beta-amyloid and in its neurotoxicity. In
      this study we aimed to investigate the clusterin/ApoJ's plasma levels in patients
      with PD to assess its potential role in fisiopathogenetic cognitive impairment. 

PMID- 24042415
TI  - [MR imaging of the Tornwaldt's cyst: retrospective study of 1300 patients].
AB  - Tornwaldt's cyst is a benign developmental lesion of the nasopharynx, most of all
      midline located, originating from an outpouching of the pharyngeal mucosa caused
      by notocord retraction. Usually, the cyst represents an incidental finding of
      magnetic resonance study. The purpose of this study is to investigate the
      differential diagnostic aspects of Tornwaldt's cysts, making a comparison with
      other diseases of nasopharynx on the basis of morphological characteristics and
      signal, contributing to the previous statistical works. 

PMID- 24042416
TI  - [Evaluation with multislice CT of the hilar pulmonary nodules for probable
      infiltration of vascular-bronchial structures].
AB  - Tumor stage is an important prognostic factor for patients suffering from lung
      cancer, because it affects the type of therapeutic treatment to be implemented.
      Computed tomography is the imaging method of choice for the staging of lung
      cancer, and for central neoplasm, it is essential to assess any possible
      involvement of bronchovascular structures that may affect operability. We report
      our experience based on the use of reconstruction algorithms for the study of the
      relationship between tumor, bronchi and adjacent vessels. 

PMID- 24042417
TI  - [Uro-CT protocol for the diagnosis of small urothelial neoplasms of urinary tract
      by quantitative analysis of contrast enhancement and correlation to the
      histological grading].
AB  - In the study of urinary tract, traditional imaging modalities still play a vital
      role in the diagnosis of urothelial tumors of the upper urinary tract; however,
      the introduction of multidetector computed tomography has greatly changed the way
      of evaluation of urological patients. In fact, by means of a multiphasic study
      protocol is possible to recognize with high sensitivity small urothelial lesions
      and, moreover, to perform at the same time, an evaluation of local and metastatic
      extension also. The evaluation of the pattern of contrast enhancement in
      addition, allows a judgement of biological aggressiveness related to tumor
      grading. 

PMID- 24042418
TI  - [Role of urographic 64 CT examination for the evaluation of kidney inflammation
      diseases].
AB  - In the study of inflammatory kidney diseases, the use of integrated imaging is
      considered the best diagnostic approach. However, given the high cost of
      radiological examinations, the radiologist is responsible for the choice of the
      best method to solve the question asked by the clinician. In this paper are
      presented the main imaging methods for the study of pyelonephritis and, based on
      our experience, it is emphasized the role of multidetector Computed Tomography
      urographic technique in the identification, characterization and subsequent
      follow-up of inflammatory kidney diseases. 

PMID- 24042419
TI  - [Ultrasound-guided biopsy of the testis: indications and results].
AB  - Ultrasound examination of the testis is the imaging modality of choice for the
      evaluation of intratesticular focal lesions. In spite of its high sensibility,
      eco-Doppler-elastography is lacking of specificity in discrimination between
      benign and malign lesions, not always allowing us to make a definitive diagnosis
      of malignancy. When a diagnostic doubt persists, for such lesions that are
      indeterminate at clinical and radiological evaluation, it is possible to recur to
      ultrasound-guided testicular needle biopsy. This paper describes the main
      application scenarios of testicular fine-needle aspiration under ultrasound
      guidance and the experience in our institute. 

PMID- 24042420
TI  - [Diagnostic value of BRAFV600E and RET/PTC oncogenes in thyroid nodule
      aspirates].
AB  - Fine-needle aspiration cytology (FNC) is the primary means to distinguish benign
      form malignant nodules. Aim of this study is to evaluate the diagnostic value of
      BRAF(V600E) and RET/PTC oncogenes in a large cohort of thyroid nodules with
      inconclusive FNC. We searched for BRAF(V600E) and RET/PTC in 299 thyroid nodule
      aspirates then removed by surgery. RET/PTC demonstrated a poor specificity. The
      search for BRAF(V600E) demonstrated to be useful in 25 cases, identifying a PTC
      in 2 false negative, 2 inadequate, 11 indeterminate and 10 suspicious FNC.
      Detection of BRAF(V600E) revealed to be a useful tool to refine inconclusive
      cytology.

PMID- 24042421
TI  - [uCT analysis of mandibular molars before and after instrumentation by Reciproc
      files].
AB  - Cleaning and shaping are important section for the root canal treatment. A number
      of different methodologies have been developed to overcome these problems,
      including the introduction of rotary instruments nickel-titanium (NiTi). In
      endodontics NiTi have been shown to significantly reduce procedural errors
      compared to manual techniques of instrumentation. The efficiency of files is
      related to many factor. Although previous investigations that have used uCT
      analysis were hampered by insufficient resolution or projection incorrect. The
      new generation of MUCT performance best offer, as micron resolution and accurate
      measurement software for evaluating the accurate anatomy of the root canal. The
      aim the paper was to evaluate the efficiency of Reciproc files in root canal
      treatment, evaluated before and after instrumentation by using MU-CT analysis. 

PMID- 24042422
TI  - [Deciduous dentition: anatomical study by MU-CT].
AB  - Endodontics is the branch of deciduous teeth pediatric dentistry that deals with
      the treatment of the root canal system. The goal of therapy is to maintain as
      long as possible the element in the dental arch to prevent alterations of
      orthognathodontic, infectious, and functional history and eruptive sequence.
      Although manual instrumentation has been widely used and still preferred by some
      practitioners, has limitations that affect the actual ability to clean the
      channel, the ability to create steps, perforations, dentinal plugs and fractures
      of the instrument. On the other hand, the disadvantages are the high cost of the
      instruments in nickel-titanium, which must be frequently replaced, and the risk
      of compromising the stability of the tooth due to an excessive consumption of
      dentinal tissue. The use of computed microtomography (MUCT) of extracted elements
      has a considerable advantage in the study of dental hard tissues. The purpose of
      this study was to analyze the anatomy of the endodontic system of the elements
      deciduous.

PMID- 24042423
TI  - [Quantitative CT perfusion measurements in characterization of solitary pulmonary
      nodules: new insights and limitations].
AB  - Although computed tomography (CT) scans remain the basis of morphologic
      evaluation in the characterization of solitary pulmonary nodules (SPNs),
      perfusion CT can represent an additional feasible technique offering reproducible
      measurements, at least in SPNs with a diameter >10 mm. In particular, CT
      perfusion could reduce the number of SPNs, diagnosed as undetermined at
      morphologic CT, avoiding long term follow-up CT, FDG-PET studies, biopsy or
      unnecessary surgery with a significant reduction in healthcare costs. In order to
      reduce the radiation dose, an optimization of the CT perfusion protocol could be
      obtained using axial mode acquisition, using shorter acquisition time and
      adaptative statistical iterative reconstruction algorithm. 

PMID- 24042424
TI  - [Sigmoid endometriosis: a diagnostic dilemma on multidetector CT].
AB  - Intestinal endometriosis represents a common condition that occurs particularly
      in women of reproductive age. The gastrointestinal tract is the third most common
      localization of endometriosis, after the ovaries and the peritoneum, and recto
      sigmoid tract is involved in 70% of cases. Recto-sigmoid endometriosis has to be
      differentiated from other diseases of large bowel, especially in patients without
      a history of endometriosis. We report a case of sigmoid endometriosis which
      represented a diagnostic dilemma on multidetector computed tomography. 

PMID- 24042425
TI  - [Lung perfusion scintigraphy in pediatric patients with congenital
      malformations].
AB  - Congenital malformations are an heterogeneous group of disorders that can lead
      changes in pulmonary perfusion and then can be evaluated with lung perfusion
      scintigraphy. We selected five patients in which the role of lung perfusion
      scintigraphy emerges as a reliable and non-invasive imaging technique. Lung
      perfusion scintigraphy is a useful tool in pediatric patients with congenital
      malformations allowing an accurate evaluation of the best therapeutic strategy
      and its results. 

PMID- 24042426
TI  - [18F-FDG PET/CT in a patient with clinical suspicion of giant cell arteritis].
AB  - We report the case of a 72 year old man with clinical suspicion of giant cell
      arteritis (GCA); in this case 18F-FDG PET/CT has been useful from the diagnosis
      to the control of the response to therapy. He performed the first 18F-FDG PET/CT
      that showed increased uptake of 18F-FDG in the aortic arch, brachial artery,
      common iliac and femoral arteries and in the temporal cerebral sites bilaterally.
      The patient then began a cortisonic therapy that led straight to the improvement
      of clinical symptoms, and repeated 18F-FDG PET/CT 3 months later the beginning of
      therapy that showed reduced uptake in the same sites of the first 18F-FDG PET/CT.
      This patient continued the cortisonic therapy, progressively reducing it until
      the definitive ending. 

PMID- 24042427
TI  - [Cerebral pseudovasculitic lesion associated with von Recklinghausen's
      neurofibromatosis: a case report].
AB  - A child with neurofibromatosis type 1 (NF1) with headache was submitted to
      magnetic resonanace imaging and a pseudovasculitic lesion was found. Vascular
      lesions are uncommon in patients with NF1 and our case highlights an even more
      rare feature of this form of vascular disease. 

PMID- 24042428
TI  - [Repair of a root perforation by using MTA: a case report].
AB  - Root perforations are accidental events that may occur during the treatment,
      causing tissue inflammation and alveolar bone loss of integrity of the
      periodontium. In such cases, the radiological evidence is fundamental in the
      formulation of the diagnosis, in the choice of therapy (surgical or non-surgical)
      and finally for the assessment of prognosis of the dental element. In non
      surgical treatment of endodontic lesions, the material used for the repair of the
      defect root should have biocompatibility, antibacterial activity, ability to
      induce healing of periodontal tissues and radiopacity. The Mineral Trioxide
      Aggregate (MTA) is a silicate-based cement introduced in dental clinical practice
      with good radiopacity, biocompatibility and bone induction. This article
      describes the use of MTA in endodontic repair of a perforation of the middle
      third root and the success of non-surgical treatment was dimonstrated
      radiographicaly. 

PMID- 24042429
TI  - [Sub-acute thyroiditis in a patient on immunosuppressive treatment].
AB  - Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory
      disease which causes the serum release of thyroidal hormones and hyperthyroidism.
      The pathogenesis of thyroid follicle damage is unclear because the exclusive
      viral action or a concomitant autoimmune component, determined by the lymphoid
      infiltrate remain to be assessed. We describe the case of a patient under
      immunosuppressive treatment, who developed sub-acute thyroiditis with hormone
      release and hyperthyroidism. The patient, while was under immunosuppressive
      treatment for kidney transplant, exhibited a clinical picture and hormonal
      profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake.
      Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De
      Quervain's thyroiditis). This case suggests the primary or even exclusive role of
      the viral infection in hormone release and hyperthyroidism in sub-acute
      thyroiditis, excluding an autoimmune component. 

PMID- 24042432
TI  - A stability-indicating reversed-phase high-performance liquid chromatography
      method for Ambrisentan: an endothelin receptor antagonist.
AB  - A stability-indicating reversed-phase high-performance liquid chromatography
      (HPLC) method was developed for the determination of ambrisentan, a drug used in
      the treatment of pulmonary hypertension. The desired chromatographic separation
      was achieved on a Kromasil C18 column (250 * 4.6 mm, 5 um) using the mobile phase
      acetonitrile-ammonium formate (pH 3.0; 0.02 M) in gradient mode. The flow rate
      was set at 1.0 mL/min, and chromatograms were extracted at 262 nm using a
      photodiode array detector. The method was successfully validated in accordance to
      International Conference on Harmonization (ICH) guidelines acceptance criteria
      for linearity, accuracy, precision, robustness and forced degradation studies,
      which further proved the stability-indicating power. Linearity of ambrisentan
      peak area responses was demonstrated within the concentration range of 25-200
      ug/mL. The limits of detection and quantitation were 0.2 and 0.6 ug/mL,
      respectively. Forced degradation studies were performed on ambrisentan bulk drug
      samples as per ICH guidelines to demonstrate the stability-indicating power of
      the HPLC method. Significant degradation was observed during acidic hydrolysis,
      neutral hydrolysis and oxidative stress. The degradation products were well
      resolved from primary peak of ambrisentan, indicating that the method is specific
      and stability indicating. The newly developed method is applicable for assay
      determination of active pharmaceutical ingredient. 

PMID- 24042431
TI  - Failure to consider the menstrual cycle phase may cause misinterpretation of
      clinical and research findings of cardiometabolic biomarkers in premenopausal
      women.
AB  - Biomarker assessment plays a critical role in the study and prevention of
      disease. However, variation in biomarkers attributable to the menstrual cycle in
      premenopausal women may impair understanding the role of certain biomarkers in
      disease development and progression. Thus, in light of the recently increasing
      evidence of menstrual cycle variability in multiple cardiometabolic biomarkers, a
      reexamination of approaches for appropriately studying and diagnosing
      cardiovascular disease in premenopausal women is warranted. We reviewed studies
      (from 1934 through 2012) evaluating changes in cardiometabolic biomarkers across
      phases of the menstrual cycle, including markers of oxidative stress, lipids,
      insulin sensitivity, and systemic inflammation. Each was observed to vary
      significantly during the menstrual cycle. For example, nearly twice as many women
      had elevated cholesterol levels warranting therapy (>=200 mg/dL) during the
      follicular phase compared with the luteal phase (14.3% vs. 7.9%), with only 3%
      having consistently high levels during all phases of the cycle. Similarly, nearly
      twice as many women were classified as being at an elevated risk of
      cardiovascular disease (high sensitivity C-reactive protein >3 mg/L) during
      menses compared with other phases (12.3% vs. 7.4%). Menstrual cycle-associated
      variability in cardiometabolic biomarkers is an important source of variability
      that should be accounted for in both research and clinical settings. 

PMID- 24042433
TI  - Cloacal dysgenesis diagnosis by prenatal ultrasound and MRI.
AB  - Cloacal malformations are a spectrum of congenital pelvic malformations that
      result from abnormal cloacal division during early embryogenesis. Depending on
      the timing of the developmental arrest, a spectrum of abnormalities can result,
      ranging from urogenital sinus malformations to cloacal dysgenesis. This case
      highlights the unique imaging features of cloacal dysgenesis, which is an
      extremely rare variant of this malformation spectrum. This variant is also the
      most severe manifestation of the cloacal malformation spectrum. 

PMID- 24042430
TI  - Postmenopausal hormone therapy is not associated with risk of all-cause dementia
      and Alzheimer's disease.
AB  - The relationship of postmenopausal hormone therapy with all-cause dementia and
      Alzheimer's disease dementia has been controversial. Given continued interest in
      the role of hormone therapy in chronic disease prevention and the emergence of
      more prospective studies, we conducted a systematic review to identify all
      epidemiologic studies meeting prespecified criteria reporting on postmenopausal
      hormone therapy use and risk of Alzheimer's disease or dementia. A systematic
      search of Medline and Embase through December 31, 2012, returned 15 articles
      meeting our criteria. Our meta-analysis of any versus never use did not support
      the hypothesis that hormone therapy reduces risk of Alzheimer's disease (summary
      estimate = 0.88, 95% confidence interval: 0.66, 1.16). Exclusion of trial
      findings did not change this estimate. There were not enough all-cause dementia
      results for a separate meta-analysis, but when we combined all-cause dementia
      results (n = 3) with Alzheimer's disease results (n = 7), the summary estimate
      remained null (summary estimate = 0.94, 95% confidence interval: 0.71, 1.26). The
      limited explorations of timing of use-both duration and early initiation-did not
      yield consistent findings. Our findings support current recommendations that
      hormone therapy should not be used for dementia prevention. We discuss trends in
      hormone therapy research that could explain our novel findings and highlight
      areas where additional data are needed. 

PMID- 24042434
TI  - Pore morphology: a vital factor in determining electrochemical properties of
      electrical double layer capacitors.
AB  - The ordered 2D reverse hexagonal pore morphology facilitates rapid ion diffusion
      more than the disordered wormhole-like pore morphology, thus leading to superior
      electrochemical properties such as rate capabilities. 

PMID- 24042435
TI  - [Pelvic floor disorders from the surgeon's viewpoint].
AB  - Pelvic floor disorders present very differently with regard to symptoms and
      manifestation. Both diagnostic and treatment options require specific experience
      and an interdisciplinary approach. Diagnostic work-up is primarily based on
      medical history, physical examination and procto-rectoscopy. Furthermore,
      endosonography and perineal sonography have also gained importance. In almost all
      cases following these basic examinations conservative therapy options should be
      considered. As the interdisciplinary concept is very important, for careful
      diagnosis of pelvic floor disorders it became crucial to find an adequate form of
      treatment. Every decision for surgical therapy should not only focus on the
      results of previous examinations but should also consider the individual
      situation of each patient. In pelvic floor disorders a large variety of symptoms
      are confronted with a vast number of different and often highly specific
      procedures. The decisions on who to treat and how to treat are not only based on
      individual patient requests and desires but also on the experience and preference
      of the surgeon. 

PMID- 24042436
TI  - [The competent surgeon. Bridging the gap between undergraduate final year and
      postgraduate surgery training].
AB  - Competency-based frameworks rely on relevant professional competency rather than
      formal regulations. The transitional phase between final year undergraduate and
      common trunk postgraduate medical training is characterized by an increase of
      professional responsibility whereby previously acquired knowledge, skills and
      abilities have to be merged and applied to patients. Undergraduate and
      postgraduate training programs should ensure a successive transfer of
      responsibility for medical practice to final year students and young residents
      depending on individual competence. The concept of entrustable professional
      activities (EPA) represents a curricular concept based on concrete medical tasks
      which may be assigned to the responsibility of the trainee. 

PMID- 24042437
TI  - Transcriptional upregulation of HIF-1alpha by NF-kappaB/p65 and its associations
      with beta-catenin/p300 complexes in endometrial carcinoma cells.
AB  - The hypoxia-inducible factor (HIF)-1alpha, which has a major role in cell
      adaptation to hypoxia, is mainly regulated at post-translational levels.
      Recently, HIF-1alpha mRNA was also shown to be upregulated by several signal
      pathways under normoxic conditions. Here we focused on relationships of HIF
      1alpha with NF-kappaB and beta-catenin signaling in endometrial carcinomas (Em
      Cas). Long-term exposure of Ishikawa cells to cobalt chloride (CoCl2), which is
      known to mimic the effect of hypoxia, caused a decrease in the growth, along with
      increased HIF-1alpha protein but not mRNA expression. In contrast, short-term
      exposure resulted in a rapid and transient increase in HIF-1alpha mRNA expression
      along with stabilization of nuclear NF-kappaB/p65 (p65). Transfection of p65
      increased HIF-1alpha expression through activation of the promoter, whereas
      overexpression of HIF-1alpha also activated NF-kappaB-dependent transcription,
      indicating the existence of a positive feedback loop. In addition, HIF-1alpha was
      indirectly associated with nuclear beta-catenin through interactions with p300,
      leading to slight enhancement of both HIF-1alpha- and beta-catenin-mediated
      transcriptional activity. In clinical samples, biphasic upregulation of HIF
      1alpha expression was observed in normal endometrial glandular components during
      the menstrual cycle, with the labeling indices showing significantly higher
      values in the early secretory stage. Significantly higher values for
      phosphorylated p65 and nuclear beta-catenin were also observed in HIF-1alpha
      positive than -negative lesions of Em Cas, in contrast to significantly lower Ki
      67 status. These data therefore suggest that transcriptional associations with
      HIF-1alpha and NF-kappaB, as well as beta-catenin/p300 complexes, may contribute
      to modulation of changes in tumor cell kinetics in response to a hypoxic
      condition in Em Cas. 

PMID- 24042438
TI  - Establishment of a system for monitoring endoplasmic reticulum redox state in
      mammalian cells.
AB  - The endoplasmic reticulum (ER) performs a critical role in the oxidative folding
      of nascent proteins, such that perturbations to ER homeostasis may lead to
      protein misfolding and subsequent pathological processes. Among the mechanisms
      for maintaining ER homeostasis is a redox regulation, which is a critical
      determinant of the fate of ER-stressed cells. Here, we report the establishment
      of a system for monitoring the ER redox state in mammalian cells. The new ER
      redox-sensing system was developed based on the previously described monitoring
      system in yeast. Our system could successfully monitor the dynamic ER redox state
      in mammalian cells. Using this system, we find that manipulation of ER oxidases
      changes the ER redox state. The mammalian ER redox-sensing system could be used
      to study the mechanisms of ER redox regulation and provide a foundation for an
      approach to develop novel therapeutic modalities for human diseases related to
      dysregulated ER homeostasis including diabetes, neurodegeneration, and Wolfram
      syndrome. 

PMID- 24042439
TI  - All-transretinoic acid ameliorates bleomycin-induced lung fibrosis by
      downregulating the TGF-beta1/Smad3 signaling pathway in rats.
AB  - The transforming growth factor-beta1 (TGF-beta1)/Smad3 signaling pathway has a
      central role in pathogenesis of lung fibrosis. In the present study, we
      investigated if all-trans retinoic acid (ATRA) could attenuate fibrosis in
      bleomycin (BLM)-induced lung fibrosis in rats through regulating TGF-beta1/Smad3
      signaling. Beginning on day 14 after BLM administration, the ATRA I and II groups
      of rats received daily oral administration of ATRA for 14 days. All rats were
      killed on day 28. Lung tissue sections were prepared and subject to histological
      assessment, and expression levels of proteins involved in the TGF-beta1 signaling
      cascade and epithelial-mesenchymal transition (EMT) were evaluated by
      transmission electron microscopy (TEM), quantitative real-time polymerase chain
      reaction (qRT-PCR), western blot procedure, and immunohistochemical or
      immunofluorescence staining. BLM significantly increased the alveolar septum
      infiltrates, inflammatory cell infiltrates, and collagen fibers. These BLM
      induced changes were significantly ameliorated by ATRA treatment. In addition,
      BLM significantly increased levels of lung fibrosis markers alpha-SMA,
      hydroxyproline (Hyp), collagen I, Snail, and Twist, whereas significantly
      decreased E-cadherin expression. ATRA treatment largely reversed BLM-induced
      changes in these lung fibrosis markers. ATRA also blocked BLM-induced activation
      of the TGF-beta1/Smad3 signaling pathway in lung tissues, including expression of
      TGF-beta1, Smad3, p-Smad3, zinc-finger E-box-binding homeobox 1 and 2 (ZEB1 and
      ZEB2), and the high-mobility group AT-hook 2 (HMGA2). Our results suggest that
      ATRA may have potential therapeutic value for lung fibrosis treatment. 

PMID- 24042440
TI  - Macroglossia in amyotrophic lateral sclerosis.
AB  - IMPORTANCE: We encountered 2 patients with amyotrophic lateral sclerosis (ALS)
      with tongue enlargement and protrusion outside the oral cavity (macroglossia). To
      our knowledge, the relationship between macroglossia and ALS has not been
      reported in the literature. The objective of this article was to describe the
      clinical characteristics, imaging, and pathology of macroglossia in ALS and to
      develop a hypothesis regarding its pathophysiology. OBSERVATIONS: Two patients
      developed progressive weakness at age 54 and 40 years. Both patients exhibited
      dysarthria, dysphagia, tongue atrophy, neck extensor weakness, and weakness of
      jaw closure during a 1-year period. Both required tracheostomy and mechanical
      ventilation and afterward developed macroglossia. A 3-dimensional-reconstructed
      sagittal computed tomographic image confirmed tongue protrusion outside the oral
      cavity with focal compression and showed the transition from the atrophied part
      of the tongue in the oropharynx to the edematous part outside the mouth. Tongue
      biopsy demonstrated fatty replacement and fascicles of degenerative muscle.
      CONCLUSIONS AND RELEVANCE: We are unaware of previous reports of macroglossia in
      ALS/motor neuron disease. Given the paucity of case material, we speculated that
      this is an extremely rare complication of ALS. Based on this series, we propose a
      pathophysiological mechanism by reviewing imaging and tongue biopsy.

PMID- 24042441
TI  - SIRT3 regulates cell proliferation and apoptosis related to energy metabolism in
      non-small cell lung cancer cells through deacetylation of NMNAT2.
AB  - Lung cancer is the leading cause of death worldwide and associated with dismal
      prognoses. As a major mitochondrial deacetylase, SIRT3 regulates the activity of
      enzymes to coordinate global shifts in cellular metabolism and has important
      implications for tumor growth. Its role as a tumor suppressor or an oncogene in
      lung cancer is unclear, especially in non-small cell lung carcinoma (NSCLC). To
      identify the mechanism of SIRT3-interacting proteins, we performed a yeast two
      hybrid screen using a human lung cDNA library. One of the positive clones encoded
      the full-length cDNA of the nicotinamide mononucleotide adenylyltransferase 2
      (NMNAT2) gene and the interaction between SIRT3 and NMNAT2 was identified. The
      interaction on growth, proliferation, apoptosis of NSCLC cell lines, and energy
      metabolism related to SIRT3 were investigated. Screening from the library
      resulted in NMNAT2 gene. We found that NMNAT2 interacts with SIRT3 both in vitro
      and in vivo; SIRT3 binds to NMNAT2 deacetylating it. Downregulation of SIRT3
      inhibited acetylation of NMNAT2 and NAD+ synthesis activity of the enzyme. Low
      expression of SIRT3 significantly inhibited mitotic entry, growth and
      proliferation of NSCLC cell lines and promoted apoptosis, which was related to
      energy metabolism involving in the interaction between SIRT3 and NMNAT2. Taken
      together, our results strongly suggest that the binding of SIRT3 with NMNAT2 is a
      novel regulator of cell proliferation and apoptosis in NSCLC cell lines,
      implicating the interaction between SIRT3 and NMNAT2, energy metabolism
      associated with SIRT3.

PMID- 24042443
TI  - Practice habits and attitudes and behaviors concerning shoulder pain in high
      school competitive club swimmers.
AB  - OBJECTIVE: The objective of this study is to describe the practice habits, injury
      frequency, and attitudes and behaviors concerning shoulder pain in high school
      aged competitive swimmers and describe the relationship between attitudes and
      behaviors. DESIGN: Cross-sectional research design. SETTING: Local swimming
      clubs. PARTICIPANTS: One hundred two swimmers, aged 13-18 years, at the top
      training level of their club team were included in the study. ASSESSMENT OF RISK
      FACTORS: Participants were given a survey with questions regarding swimming
      practice and attitudes and behaviors concerning shoulder pain. MAIN OUTCOME
      MEASURES: Practice habits (yards/week, practice/week, dry-land and weight/week,
      and months swimming/year) and attitudes and behaviors concerning shoulder pain.
      RESULTS: Subjects completed an average of 6.89 +/- 1.41 swimming practices/wk of
      6000 to 7000 yd/practice. The majority of swimmers believe that mild and moderate
      shoulder pain is normal in swimming and should be tolerated to complete practice,
      while a majority responded that they swim with shoulder pain. Seventy-three
      percent of swimmers reported using pain medication to manage their shoulder pain.
      There was a significant correlation between attitude and behaviors of moderate
      and severe shoulder pain. CONCLUSIONS: Club swimmers have a high frequency of
      practices, comparable to collegiate and professional swimmers. They believe that
      shoulder pain is normal and should be tolerated to complete practice. The
      association between the swimmers' attitudes and behaviors indicates that the
      interventions that educate the swimmers, coaches, and parents may be effective in
      changing their attitudes and ultimately their behaviors, decreasing the number of
      athletes who train with shoulder pain.

PMID- 24042442
TI  - Endoscopic repair of a chronic incomplete proximal hamstring avulsion in a
      cheerleader.
AB  - : Injuries to the hamstring muscle are common among athletes, especially strains
      at the myotendinal junction that respond well to nonoperative treatment. Proximal
      hamstring avulsion injuries can be severely debilitating, and the role of
      endoscopic treatment for these injuries has not been explored. This article
      describes the case report of a 16-year-old girl who was diagnosed with incomplete
      proximal hamstring avulsion showing no improvement despite extensive nonoperative
      treatment. The patient was treated by endoscopic repair in the prone position
      using a novel technique. Her preoperative pain on the ischial tubercle and while
      sitting disappeared completely 3 months postoperatively. 

PMID- 24042444
TI  - Physician-prescribed medication use by the Finnish Paralympic and Olympic
      athletes.
AB  - OBJECTIVE: Data about medication use by Paralympic athletes (PAs) are limited and
      no data concerning medication use outside Paralympics exist. The objective of the
      current study was to compare the use of physician-prescribed medication in PAs
      and Olympic athletes (OAs). DESIGN: A cross-sectional comparative study. SETTING:
      Finnish PAs and OAs receiving financial support from the Finnish Olympic and
      Paralympic committee in 2006 and 2009, respectively. PARTICIPANTS: A total of 92
      PAs (response rate, 75.0%; 92 of 123) and 372 OAs (response rate, 91.9%; 372 of
      405) participated. ASSESSMENT OF RISK FACTORS: Age, sex, and type of athlete (PA
      vs OA) were included as independent covariates in the logistic regression model
      analysis. MAIN OUTCOME MEASURES: The use of physician-prescribed medication among
      athletes during the previous 7 days and 12 months. RESULTS: Among the PAs, the
      use of physician-prescribed medicines (48.9% vs 33.3%; adjusted odds ratio, 1.99;
      95% confidence interval, 1.13-3.51), painkillers (2.61; 1.18-5.78), oral
      antibiotics (4.10; 1.30-12.87), and anti-epileptic medicines (37.09; 5.92-232.31)
      were more common than among the OAs during the previous 7 days. Paralympic
      athletes had used significantly less asthma medicines than the OAs during the
      previous 7 days (4.3% vs 11.0%; adjusted odds ratio, 0.30; 95% confidence
      interval, 0.10-0.96). CONCLUSIONS: The use of any physician-prescribed medicines,
      especially those to treat chronic diseases, seems to be more common among the PAs
      than the OAs. Paralympic athletes use significantly less asthma medicines than
      OAs.

PMID- 24042445
TI  - Retina-simulating phantom for optical coherence tomography.
AB  - Optical coherence tomography (OCT) is a rapidly growing imaging modality,
      particularly in the field of ophthalmology. Accurate early diagnosis of diseases
      requires consistent and validated imaging performance. In contrast to more well
      established medical imaging modalities, no standardized test methods currently
      exist for OCT quality assurance. We developed a retinal phantom which mimics the
      thickness and near-infrared optical properties of each anatomical retinal layer
      as well as the surface topography of the foveal pit. The fabrication process
      involves layer-by-layer spin coating of nanoparticle-embedded silicone films
      followed by laser micro-etching to modify the surface topography. The thickness
      of each layer and dimensions of the foveal pit are measured with high precision.
      The phantom is embedded into a commercially available, water-filled model eye to
      simulate ocular dispersion and emmetropic refraction, and for ease of use with
      clinical OCT systems. The phantom was imaged with research and clinical OCT
      systems to assess image quality and software accuracy. Our results indicate that
      this phantom may serve as a useful tool to evaluate and standardize OCT
      performance.

PMID- 24042446
TI  - Elastographic mapping in optical coherence tomography using an unconventional
      approach based on correlation stability.
AB  - An approach to elastographic mapping in optical coherence tomography (OCT) using
      comparison of correlation stability of sequentially obtained intensity OCT images
      of the studied strained tissue is discussed. The basic idea is that for stiffer
      regions, the OCT image is distorted to a smaller degree. Consequently, cross
      correlation maps obtained with compensation of trivial translational motion of
      the image parts using a sliding correlation window can represent the spatial
      distribution of the relative tissue stiffness. An important advantage of the
      proposed approach is that it allows one to avoid the stage of local-strain
      reconstruction via error-sensitive numerical differentiation of experimentally
      determined displacements. Another advantage is that the correlation stability
      (CS) approach intrinsically implies that for deformed softer tissue regions,
      cross-correlation should already be strongly decreased in contrast to the
      approaches based on initial reconstruction of displacements. This feature
      determines a much wider strain range of operability than the proposed approach
      and is favorable for its free-hand implementation using the OCT probe itself to
      deform the tissue. The CS approach can be implemented using either the image
      elements reflecting morphological structure of the tissue or performing the
      speckle-level cross-correlation. Examples of numerical simulations and
      experimental demonstrations using both phantom samples and in vivo obtained OCT
      images are presented.

PMID- 24042447
TI  - Quantitative evaluation of dental abfraction and attrition using a swept-source
      optical coherence tomography system.
AB  - A fast swept-source optical coherence tomography (SS-OCT) system is employed to
      acquire volumes of dental tissue, in order to monitor the temporal evolution of
      dental wear. An imaging method is developed to evaluate the volume of tissue lost
      in ex vivo artificially induced abfractions and attritions. The minimal volume
      (measured in air) that our system could measure is 2352 MUm3. A volume of 25,000
      A-scans is collected in 2.5 s. All these recommend the SS-OCT method as a
      valuable tool for dynamic evaluation of the abfraction and attrition with
      remarkable potential for clinical use.

PMID- 24042448
TI  - Systematic investigation of DNAs with modified cytosines under hot alkali
      treatment.
AB  - We have conducted the first systematic investigation of DNAs with modified
      cytosines, including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5
      formylcytosine (5fC) and 5-carboxylcytosine (5caC), under hot alkali treatment. 

PMID- 24042449
TI  - The global NAFLD epidemic.
AB  - NAFLD is a clinical syndrome characterized by predominant macrovesicular
      steatosis of the liver. The clinical and histological phenotypes of NAFLD extend
      from a nonalcoholic fatty liver to NASH. Although the prevalence of NAFLD is
      increasing globally, and it is set to become the predominant cause of chronic
      liver disease in many parts of the world, the epidemiology and demographic
      characteristics of NAFLD vary worldwide. Indeed, the condition is associated with
      obesity and insulin resistance in most cases in the Western world, but the
      disease manifests at a lower BMI in Asian countries and many patients do not seem
      to have insulin resistance as determined using conventional methods. The
      similarities and differences in the epidemiology of NAFLD in different regions of
      the world are discussed and the potential role of genetics and insulin resistance
      in disease progression is also presented.

PMID- 24042452
TI  - Functional genomic analyses of the gut microbiota for CRC screening.
AB  - The evidence for a strong correlation between the gut microbiota and colorectal
      carcinogenesis is quickly gathering pace. This correlation raises important
      questions, such as whether analysis of the microbiota can be used for screening
      purposes, and whether targeted intervention can influence the risk of development
      and progression of neoplasia. The recovery of several pathobionts-such as members
      of the different bacterial phyla Proteobacteria, Bacteroidetes and Fusobacteria
      from the tumour microenvironment of patients with colorectal cancer (CRC) now
      provides a link between specific microbial colonization and cancer. However,
      other intestinal bacteria belonging to another major intestinal phylum,
      Firmicutes, might be effective in the treatment of pathogenic inflammation
      related to CRC. Future approaches based on the analysis of the gut microbiota of
      patients with CRC combined with large human cohort studies might open up new
      possibilities for further prophylactic, screening and treatment strategies.

PMID- 24042455
TI  - A novel method to fabricate discrete porous carbon hemispheres and their
      electrochemical properties as supercapacitors.
AB  - A simple and efficient method to produce discrete, hierarchical porous carbon
      hemispheres (CHs) with high uniformity has been successfully developed by
      constructing nanoreactors and using low crosslinked poly(styrene-co
      divinylbenzene) (P(St-co-DVB)) capsules as precursors. The samples are
      characterized by scanning and transmission electron microscopy, Fourier transform
      infrared and Raman spectroscopy, X-ray diffraction, and N2 adsorption and
      desorption. Considering their application, the cyclic voltammetry and
      electrochemical impedance spectroscopy characterization are tested. The
      experimental results show that the achievement of discrete and perfect carbon
      hemispheres is dependent on the proper amount of DVB in the P(St-co-DVB)
      capsules, which can contribute to the ideal thickness or mechanical strength of
      the shells. When the amount of DVB is 35 wt% in the precursors, a high Brunauer
      Emmett-Teller surface area of 676 m(2) g(-1) can be obtained for the carbon
      hemispheres, and the extremely large pore volume of 2.63 cm(3) g(-1) can also be
      achieved at the same time. The electrochemical test shows the carbon hemispheres
      have a higher specific capacitance of ca. 83 F g(-1) at 10 mV s(-1), compared to
      other carbon materials. So this method supplies a platform to extend the
      fabrication field of carbon materials and supplies more chances for the
      application of carbon materials including carbon hemispheres that are important
      components and substrates for supercapacitors. 

PMID- 24042453
TI  - Obesity: fatty liver and the metabolic syndrome-fructose at fault?

PMID- 24042456
TI  - Structure and spectroscopy of hydrated neptunyl(VI) nitrate complexes.
AB  - Complexation between hexavalent neptunium and nitrate was studied in aqueous
      nitric acid solution using optical absorption, vibrational and X-ray absorption
      spectroscopies. Distributions of aqueous [NpO2](2+), [NpO2(NO3)](+) and
      [NpO2(NO3)2] species were obtained as a function of nitric acid concentration
      between 0 and 14 M. The crystal structure of [NpO2(NO3)2(H2O)2].H2O was
      determined. 

PMID- 24042457
TI  - Hyperglycemia decreases the expression of ATP synthase beta subunit and enolase 2
      in glomerular epithelial cells.
AB  - Glomerular epithelial cells (GECs) are known to play a key role in maintaining
      the structure and function of the glomerulus. GEC injury induced by hyperglycemia
      is present in early-stage diabetic nephropathy (DN), which is the most common
      cause of renal failure. In an attempt to identify target proteins involved in the
      pathogenesis of GEC injury at early DN, we performed the proteomic analysis using
      primary cultures of GECs, prepared from the dissected rat glomeruli. The protein
      expression profiles in the two-dimensional electrophoresis gels were compared
      between GECs treated for three days with normal glucose (5 mM) and those with
      high glucose (30 mM) concentrations. These concentrations correspond to blood
      glucose concentrations under normoglycemia and hyperglycemia, respectively.
      Proteins with differential expression levels were identified using ESI-Q-TOF
      tandem mass spectrometry. The primary GECs cultured in hyperglycemic conditions
      showed cellular hypertrophy and increased production of reactive oxygen species,
      both of which reflect the GEC injury. Our proteomic analysis identified eight
      proteins with differential expression profiles, depending on glucose
      concentrations. Among them, we selected ATP synthase beta subunit and enolase 2
      that are related to energy metabolism and are down-regulated under hyperglycemia,
      and confirmed that hyperglycemia decreased the expression levels of ATP synthase
      beta subunit and enolase 2 proteins by western blotting analysis. Hyperglycemia
      may impair mitochondrial function and alter glycolysis in GECs by down-regulating
      the expression of ATP synthase beta subunit and enolase 2. The present study may
      provide a better understanding of the pathogenic mechanisms of GEC injury in
      early DN. 

PMID- 24042458
TI  - A novel approach towards white photoluminescence and electroluminescence by
      controlled protonation of a blue fluorophore.
AB  - We presented a novel and simple approach towards white photoluminescence and
      electroluminescence based on blue emissive materials through controlled acid
      protonation; and this methodology has potential applicability in fabricating
      white OLEDs considering the simplicity of both material design and device
      fabrication. 

PMID- 24042460
TI  - Unique peptide-binding motif for Mamu-B*037:01: an MHC class I allele common to
      Indian and Chinese rhesus macaques.
AB  - Indian and Chinese rhesus macaques are often used in biomedical research. Genetic
      analyses of the major histocompatibility class I region have revealed that these
      macaques display a substantial level of polymorphism at Mamu-A and Mamu-B loci,
      which have been subject to duplication. Only a few Mamu class I allotypes are
      characterised for their peptide-binding motifs, although more information of this
      nature would contribute to a better interpretation of T cell-mediated immune
      responses. Here, we present the results of the characterisation of the functional
      properties of Mamu-B*037:01, an allotype commonly encountered in rhesus macaques
      of Indian and Chinese origin. Mamu-B*037:01 is seen to have a strong preference
      for acidic amino acids at the third residue, and for arginine, lysine, and
      tyrosine at the carboxyl terminus. This peptide-binding motif is not described in
      the human population. 

PMID- 24042461
TI  - Identification of Mamu-DPA1, Mamu-DQA1, and Mamu-DRA alleles in a cohort of
      Chinese rhesus macaques.
AB  - Rhesus macaques have long been used as animal models for various human diseases;
      the susceptibility and/or resistance to some of these diseases are related to the
      major histocompatibility complex (MHC). To gain insight into the MHC background
      and to facilitate the experimental use of Chinese rhesus macaques, Mamu-DPA1,
      Mamu-DQA1, and Mamu-DRA alleles were investigated in 30 Chinese rhesus macaques
      by gene cloning and sequencing. A total of 14 Mamu-DPA1, 17 Mamu-DQA1, and 9 Mamu
      DRA alleles were identified in this study. Of these alleles, 22 novel sequences
      have not been documented in earlier studies, including nine Mamu-DPA1, ten Mamu
      DQA1, and three Mamu-DRA alleles. Interestingly, like Mafa-DQA1 and Mafa-DPA1,
      more than two Mamu-DQA1 and Mamu-DPA1 alleles were detected in one animal in this
      study, which suggested that they might represent gene duplication. If our
      findings can be validated by other studies, it will further increase the number
      of known Mamu-DPA1 and Mamu-DQA1 polymorphisms. Our data also indicated
      significant differences in MHC class II allele distribution among the Chinese
      rhesus macaques, Vietnamese cynomolgus macaques, and the previously reported
      rhesus macaques, which were mostly of Indian origin. This information will not
      only promote the understanding of Chinese rhesus macaque MHC diversity and
      polymorphism but will also facilitate the use of Chinese rhesus macaques in
      studies of human disease. 

PMID- 24042462
TI  - Contextual effect of repression of bone morphogenetic protein activity in
      prostate cancer.
AB  - Several studies have focused on the effect of bone morphogenetic protein (BMP) on
      prostate cancer homing and growth at distant metastatic sites, but very little
      effect at the primary site. Here, we used two cell lines, one (E8) isolated from
      a primary tumor and the other (cE1) from a recurrent tumor arising at the primary
      site, both from the conditional Pten deletion mouse model of prostatic
      adenocarcinoma. Over-expression of the BMP antagonist noggin inhibited
      proliferation of cE1 cells in vitro while enhancing their ability to migrate. On
      the other hand, cE1/noggin grafts grown in vivo showed a greater mass and a
      higher proliferation index than the cE1/control grafts. For suppression of BMP
      activity in the context of cancer-associated fibroblasts (CAFs), we used noggin
      transduced CAFs from the same mouse model to determine their effect on E8- or cE1
      induced tumor growth. CAF/noggin led to increased tumor mass and greater de
      differentiation of the E8 cell when compared with tumors formed in the presence
      of CAF/control cells. A trend of increase in the size of the tumor was also noted
      for cE1 cells when inoculated with CAF/noggin. Together, the results may point to
      a potential inhibitory role of BMP in the growth or re-growth of prostate tumor
      at the primary site. Additionally, results for cE1/noggin, and cE1 mixed with
      CAF/noggin, suggested that suppression of BMP activity in the cancer cells may
      have a stronger growth-enhancing effect on the tumor than its suppression in the
      fibroblastic compartment of the tumor microenvironment.

PMID- 24042464
TI  - Chronic kidney disease: fluid in chronic kidney disease-how much is too much?
AB  - A new study provides cogent evidence that fluid overload-measured using
      bioimpedance spectroscopy-promotes progression of chronic kidney disease (CKD). A
      prospective randomized trial is warranted to assess the effect of interventions
      to reduce fluid overload on disease progression in patients with CKD.

PMID- 24042463
TI  - RelB, together with RelA, sustains cell survival and confers proteasome inhibitor
      sensitivity of chronic lymphocytic leukemia cells from bone marrow.
AB  - Although the biological factors that contribute to the pathogenesis of chronic
      lymphocytic leukemia (CLL) remain widely unresolved, it has been suggested that
      dysregulated cell survival and proliferation are fundamental to this process.
      Constitutive classical nuclear factor kappa-light-chain-enhancer of activated B
      cells (NF-kappaB) activation protects CLL B-cells from cell death and plays a
      critical role in the acquisition of chemoresistance. RelB, representing the
      alternative NF-kappaB activity, functions specifically in lymphoid organogenesis
      and B-cell maturation. RelB indeed plays a tumor-supportive role and confers
      radiation resistance in tumors. However, the involvement of RelB in CLL has not
      been addressed. Here, we analyzed the NF-kappaB activation in 67 of CLL bone
      marrow (BM). Both the RelA and RelB activity were detected in CLL B-cells from
      BM, in spite of inevitable variability. Low RelB activity was linked to a
      favorable prognosis of CLL. The migration and adhesion abilities of CLL B-cells
      were not affected by the RelB activity. High RelB activity, together with the
      RelA activity, maintained basal survival of cells. The induction of RelA and RelB
      expression in the nucleus was responsible for better survival of CLL B-cells
      supported by bone marrow stromal cells. In addition, the presence of high RelB
      activity in CLL B-cells was correlated with sensitivity to proteasome inhibitor
      but not fludarabine. Taken together, we provided evidences that not only RelA but
      also RelB, subunits of NF-kappaB family, played an important role in the cellular
      behaviors of CLL cells from BM. The strength of RelB activity influenced the
      prognosis of CLL patients. KEY MESSAGE: RelB, with RelA activity, maintained the
      basal survival of CLL cells from BM. RelB, with RelA, conferred the proteasome
      inhibitor sensitivity of CLL cells. Induction of RelA and RelB was responsible
      for the better survival of CLL B-cells. The strength of RelB activity influenced
      the prognosis of CLL patients.

PMID- 24042465
TI  - Renal fibrosis: KIM-1 expression links kidney injury with CKD in mice.

PMID- 24042466
TI  - Transplantation: socioeconomic factors most important.

PMID- 24042467
TI  - Diabetes: Assessing renal risk in patients with type 2 diabetes.

PMID- 24042468
TI  - Intradural, extramedullary anaplastic astrocytoma arising from the first sacral
      nerve root.

PMID- 24042469
TI  - 2,4-Diamino-6,7-dimethylpteridine as a fluorescent ligand for binding and sensing
      an orphan cytosine in RNA duplexes.
AB  - We report on a new fluorescent ligand, 2,4-diamino-6,7-dimethylpteridine, that
      can strongly and selectively bind to an orphan cytosine opposite an abasic site
      in RNA duplexes. We describe a significant effect of the substituents attached to
      the pteridine ring on the binding behavior in comparison with a structurally
      similar pteridine derivative. 

PMID- 24042470
TI  - Telomerase regulation: a key to inhibition? (Review).
AB  - Telomerase has been recognized as a common factor in most tumor cells, and in
      turn a distinctive feature with respect to non-malignant cells. This feature has
      made telomerase a promising target for cancer therapy. Telomerase studies
      revealed that it is a multi-subunit complex possessing different levels of
      regulation, including control of expression, phosphorylation state, assembly and
      transportation to sites of activity. Thus, we emphasize that targeting telomerase
      expression or activity is not the only way to shorten telomeres, induce cell
      senescence and apoptosis. Therefore, there are multiple sites capable of allowing
      the modulation of its enzymatic activity. In the development of strategies based
      on the regulation of telomerase activity the understanding of the mechanisms
      regulating their subunits is essential. Based on this, in this review we
      summarize the current state of knowledge of some regulatory mechanisms of the
      components of the telomerase complex, and hypothetize their potential therapeutic
      application against cancer. 

PMID- 24042471
TI  - Mixed addenda polyoxometalate "solutions" for stationary energy storage.
AB  - A series of redox flow batteries utilizing mixed addenda (vanadium and tungsten),
      phosphorus-based polyoxometalates (A-alpha-PV3W9O40(6-), B-alpha-PV3W9O40(6-),
      and P2V3W15O62(9-)) were prepared and tested. Cyclic voltammetry and bulk
      electrolysis experiments on the Keggin compounds (A-alpha-PV3W9O40(6-) and B
      alpha-PV3W9O40(6-)) established that the vanadium centers of these compounds
      could be used as the positive electrode (PV(IV)3W(VI)9O40(9-)/PV(V)3W(VI)9O40(6
      )), and the tungsten centers could be used as the negative electrode
      (PV(IV)3W(VI)9O40(9-)/PV(IV)3W(V)3W(VI)6O40(12-)) since these electrochemical
      processes are separated by about 1 V. The results showed that A-alpha-PV3W9O40(6
      ) (where A indicates adjacent, corner-sharing vanadium atoms) had coulombic
      efficiencies (charge in divided by charge out) above 80%, while the coulombic
      efficiency of B-alpha-PV3W9O40(6-) (where B indicates adjacent edge-sharing
      vanadium atoms) fluctuated between 50% and 70% during cycling. The
      electrochemical yield, a measurement of the actual charge or discharge observed
      in comparison with the theoretical charge, was between 40% and 50% for A-alpha
      PV3W9O40(6-), and (31)P NMR showed small amounts of PV2W10O40(5-) and PVW11O40(4
      ) formed with cycling. The electrochemical yield for B-alpha-PV3W9O40(6-)
      decreased from 90% to around 60% due to precipitation of the compound on the
      electrode, but there were no decomposition products detected in the solution by
      (31)P NMR, and infrared data on the electrode suggested that the cluster remained
      intact. Testing of P2V3W15O62(9-) (Wells-Dawson structure) suggested higher
      charge density clusters were not as suitable as the Keggin structures for a redox
      flow battery due to the poor stability and inaccessibility of the highly reduced
      materials. 

PMID- 24042472
TI  - Characteristics of pemetrexed transport by renal basolateral organic anion
      transporter hOAT3.
AB  - PURPOSE: Pemetrexed transport by human organic anion transporters, hOAT1
      (SLC22A6) and hOAT3 (SLC22A8), were characterized in comparison with
      methotrexate. METHODS: Accumulation of pemetrexed and methotrexate in hOAT1- and
      hOAT3-expressing cells were evaluated. Pemetrexed and methotrexate were
      determined by HPLC. Kinetic parameters were calculated by Eadie-Hofstee plot.
      RESULTS: When HEK-hOAT3 and -hOAT1 cells were incubated with 100 uM pemetrexed
      for 30 min, pemetrexed was accumulated at 14- and 1.7-fold greater than that in
      control cells, respectively. Pemetrexed and methotrexate transport by hOAT3 was
      saturated at high concentrations with apparent Km values 28.2 uM and 76.6 uM,
      respectively. In addition, intrinsic activity (Vmax/Km) of pemetrexed and
      methotrexate transport by hOAT3 was 4.82 and 0.42 ul/min/mg protein,
      respectively, suggesting 11-fold higher transport of pemetrexed than methotrexate
      by hOAT3. Furthermore, loxoprofen, ibuprofen, pravastatin, and cefazolin,
      transport substrates of hOAT3, inhibited pemetrexed transport by hOAT3 with IC50
      values, 34.2, 27.9, 76.3 and 650 uM, respectively. CONCLUSIONS: Pemetrexed is a
      superior substrate to methotrexate for hOAT3. Loxoprofen, ibuprofen, and
      cefazolin could cause drug-drug interactions when attaining high blood
      concentrations.

PMID- 24042473
TI  - Utility of cryopreserved hepatocytes suspended in serum to predict hepatic
      clearance in dogs and monkeys.
AB  - An in vitro-in vivo correlation analysis between observed and predicted metabolic
      clearance in multiple preclinical species including dogs and monkeys constitutes
      an integral part of prediction for the pharmacokinetics in humans by using liver
      derived in vitro preparations. Empirical values of the scaling factor for the
      extrapolation of metabolic (intrinsic) clearance in the in vitro preparation to
      that for whole liver were calculated for each preparation of 8 and 5
      cryopreserved dog and monkey hepatocytes, respectively, by optimizing the
      objective function of average fold error between predicted and observed metabolic
      (intrinsic) clearance for eight and 11 standard compounds for dogs and monkeys,
      respectively. Thus obtained values of the scaling factor ranged from 5.46 * 10(9)
      to 19.9 * 10(9) cells/kg body weight with an average of 10.3 * 10(9) cells/kg
      body weight in dogs, and the value ranged from 2.36 * 10(9) to 4.21 * 10(9)
      cells/kg body weight with an average of 3.17 * 10(9) cells/kg body weight in
      monkeys, which were both consistent with biologically calculated values in
      corresponding species. These results demonstrated the utility of commercially
      available cryopreserved preparations of dog and monkey hepatocytes for the in
      vitro-in vivo correlation analyses with the aid of empirically or biologically
      obtained scaling factors at the early development stage of new drug candidates.

PMID- 24042474
TI  - Manipulation of domain wall mobility by oxygen vacancy ordering in multiferroic
      YMnO3.
AB  - The mobility of the ferroelectric domain phases and the local conductivity of
      ferroelectric domain walls in multiferroic YMnO3 crystals grown in air and
      reduced atmosphere were studied by piezoresponse force microscopy (PFM), tip
      enhanced Raman spectroscopy (TERS) and conductive atomic force microscopy (CAFM).
      Oxygen vacancies were found to reduce the strength of 4d-2p (Y(3+)-O(2-))
      hybridization and structural trimerization distortion, leading to the
      disappearance of the six wedge-shaped ferroelectric domain phases in oxygen
      deficient YMnO3-delta crystals. We observed anisotropic domain wall motion such
      that the wedge-shaped domain configuration joined at one point could be changed
      to the stripe domain configuration by applying high electric fields in oxygen
      deficient YMnO3-delta single crystals. The local conductivity of the domain walls
      increased significantly in poled YMnO3-delta single crystals. The straight
      conductive domain walls in YMnO3-delta, instead of the twisted insulating ones in
      the stoichiometric crystal, are induced by the ordered oxygen vacancies which are
      verified by TERS measurements. 

PMID- 24042477
TI  - A useful method integrating production and immobilization of recombinant
      cellulase.
AB  - The development of cellulase-based bioprocess is afflicted by the processing
      efficiency of enzymes. To address this issue, a method based on artificial oil
      bodies (AOBs) was proposed to integrate production and immobilization of
      recombinant cellulase. First, the heterologous endoglucanase (celA),
      cellobiohydrolase (celK), and beta-glucosidase (gls) genes were individually
      fused with oleosin, a structural protein of plant seed oils. After expression in
      Escherichia coli, each fusion protein of insolubility was mixed together with
      plant oils. AOBs were assembled by subjecting the mixture to sonication.
      Consequently, active CelA, CelK, and Gls were resumed and co-immobilized on AOBs
      surface. Finally, the assembly condition (including the protein ratio) and the
      reaction condition were further optimized by response surface methodology. The
      resulting AOBs-bound cellulase remained stable for 4 cycles of cellulose
      hydrolyzed reactions. Overall, the result shows a promise of this proposed
      approach for processing recombinant cellulase, which may provide a facile method
      to investigate optimum combination of cellulase components towards various
      cellulosic materials.

PMID- 24042478
TI  - Neural mechanisms underlying stress resilience in Ahi1 knockout mice: relevance
      to neuropsychiatric disorders.
AB  - The Abelson helper integration site 1 (AHI1) gene has a pivotal role in brain
      development. Studies by our group and others have demonstrated association of
      AHI1 with schizophrenia and autism. To elucidate the mechanism whereby alteration
      in AHI1 expression may be implicated in the pathogenesis of neuropsychiatric
      disorders, we studied Ahi1 heterozygous knockout (Ahi1(+/-)) mice. Although their
      performance was not different from wild-type mice on tests that model classical
      schizophrenia-related endophenotypes, Ahi1(+/-) mice displayed an anxiolytic-like
      phenotype across different converging modalities. Using behavioral paradigms that
      involve exposure to environmental and social stress, significantly decreased
      anxiety was evident in the open field, elevated plus maze and dark-light box, as
      well as during social interaction in pairs. Assessment of core temperature and
      corticosterone secretion revealed a significantly blunted response of the
      autonomic nervous system and the hypothalamic-pituitary-adrenal axis in Ahi1(+/-)
      mice exposed to environmental and visceral stress. However, response to centrally
      acting anxiogenic compounds was intact. On resting-state functional MRI,
      connectivity of the amygdala with other brain regions involved in processing of
      anxiogenic stimuli and inhibitory avoidance learning, such as the lateral
      entorhinal cortex, ventral hippocampus and ventral tegmental area, was
      significantly reduced in the mutant mice. Taken together, our data link Ahi1
      under-expression with a defect in the process of threat detection. Alternatively,
      the results could be interpreted as representing an anxiety-related
      endophenotype, possibly granting the Ahi1(+/-) mouse relative resilience to
      various types of stress. The current knockout model highlights the contribution
      of translational approaches to understanding the genetic basis of emotional
      regulation and its associated neurocircuitry, with possible relevance to
      neuropsychiatric disorders.

PMID- 24042480
TI  - Neuro-oncology: Glioblastoma prognosis linked to neuronal PD-L1 expression in
      tumour-adjacent tissue.

PMID- 24042479
TI  - FAAH selectively influences placebo effects.
AB  - Endogenous opioid and cannabinoid systems are thought to act synergistically
      regulating antinociceptive and reward mechanisms. To further understand the human
      implications of the interaction between these two systems, we investigated the
      role of the common, functional missense variant Pro129Thr of the gene coding
      fatty acid amide hydrolase (FAAH), the major degrading enzyme of
      endocannabinoids, on psychophysical and neurotransmitter (dopaminergic, opioid)
      responses to pain and placebo-induced analgesia in humans. FAAH Pro129/Pro129
      homozygotes, who constitute nearly half of the population, reported higher
      placebo analgesia and more positive affective states immediately and 24 h after
      placebo administration; no effects on pain report in the absence of placebo were
      observed. Pro129/Pro129 homozygotes also showed greater placebo-induced MU
      opioid, but not D(2/3) dopaminergic, enhancements in neurotransmission in regions
      known involved in placebo effects. These results show that a common genetic
      variation affecting the function of the cannabinoid system is serving as a probe
      to demonstrate the involvement of cannabinoid and opioid transmitters on the
      formation of placebo effects.

PMID- 24042481
TI  - Neuroimmunology: Aquaporin-4-antibody-seronegative neuromyelitis optica is less
      common than previously thought.

PMID- 24042482
TI  - Neuropsychiatric disorders: Cell-based transplants restore neuronal functioning
      in a rat model of schizophrenia.

PMID- 24042484
TI  - Prevalence of keratoconus in a population-based study in Shahroud.
AB  - PURPOSE: To determine the prevalence of keratoconus in the 40- to 64-year-old
      population of Shahroud, Iran. METHODS: This study was done cross sectionally
      based on the data from the first phase of the Shahroud Eye Cohort Study. In this
      study, 6311 patients were selected using random cluster sampling, and 5190
      patients (response rate = 82.2%) participated in the study. Here, the analysis
      was done on data pertaining to those whose topographic map (with Pentacam) had no
      errors. These patients were categorized as keratoconus, forme fruste keratoconus,
      and non-keratoconus. RESULTS: After applying the exclusion criteria, data from
      4592 patients with a mean age of 50.83 +/- 0.12 years were analyzed. Of these, 35
      patients (0.76%) were diagnosed with keratoconus in at least 1 eye, and 47
      patients (1.02%) were identified as having forme fruste keratoconus. The
      prevalence of keratoconus was 0.72% (95% confidence interval, 0.35-1.09) in men,
      and 0.79% (95% confidence interval, 0.43-1.15) in women (P = 0.793). The mean age
      of the keratoconic patients was 47.6, which was significantly lower than 50.9 of
      normal individuals (P < 0.001). The mean maximum keratometry and central corneal
      thickness in patients with keratoconus were 48.67 +/- 3.6 diopters and 470 +/- 29
      MUm, respectively. Keratoconus was associated with an 8.1 greater odds of visual
      impairment (P < 0.001). CONCLUSIONS: The prevalence of keratoconus in the
      Shahroud population is far higher than in western populations. Because of the
      high odds of visual impairment in this population, it can be a serious warning
      for the need to assess the prevalence and causes of keratoconus in the Middle
      Eastern region.

PMID- 24042483
TI  - Cortical spreading depression and migraine.
AB  - Cortical spreading depression (CSD), a slowly propagated wave of depolarization
      followed by suppression of brain activity, is a remarkably complex event that
      involves dramatic changes in neural and vascular function. Since its original
      description in the 1940s, CSD has been hypothesized to be the underlying
      mechanism of the migraine aura. Substantial evidence from animal models provides
      indirect support for this hypothesis, and studies showing that CSD is common in
      humans with brain injury clearly demonstrate that the phenomenon can occur in the
      human brain. Considerable uncertainty about the role of CSD in migraine remains,
      however, and key questions about how this event is initiated, how it spreads, and
      how it might cause migraine symptoms remain unanswered. This Review summarizes
      current concepts of CSD and its potential roles in migraine, and addresses
      ongoing studies aimed at a clearer understanding of this fundamental brain
      phenomenon. 

PMID- 24042485
TI  - In vivo three-dimensional corneal epithelium imaging in normal eyes by anterior
      segment optical coherence tomography: a clinical reference study.
AB  - PURPOSE: To evaluate the safety and efficacy of real-time measurement of corneal
      epithelial thickness and investigate the distribution characteristics in a large
      normal-eye population using a clinically available spectral-domain anterior
      segment optical coherence tomography (AS OCT) system. METHODS: Corneal epithelial
      thickness distribution and topographic thickness variability were clinically
      investigated using AS OCT imaging in 373 patients with normal, healthy eyes.
      Descriptive statistics investigated 3 sets of subgroups, male (n = 171) and
      female (n = 202), younger (n = 194) and older (n = 179), right eyes (n = 195) and
      left eyes (n = 197). RESULTS: Pupil center epithelial thickness repeatability was
      an average 0.88 +/- 0.71 MUm; a similar repeatability was noted for the superior,
      inferior, maximum, and minimum epithelial thickness. On average, the pupil center
      epithelial thickness was 53.28 +/- 3.34 MUm, superior 51.86 +/- 3.78 MUm,
      inferior 53.81 +/- 3.44 MUm, minimum 48.65 +/- 4.54 MUm, maximum 56.35 +/- 3.80
      MUm, and topographic variability was 1.78 +/- 0.78 MUm. Small differences were
      noted between male (average center 54.10 +/- 3.34 MUm) and female (52.58 +/- 3.19
      MUm) subjects. The topographic thickness variability seems to increase with age:
      younger group, 1.65 +/- 0.83 MUm; older group, 1.93 +/- 0.90 MUm (P = 0.173).
      CONCLUSIONS: We present a comprehensive investigation of corneal epithelial
      thickness distribution characteristics in a healthy, untreated human eye
      population by using in vivo, clinically available Fourier-domain AS OCT. The 3
      dimensional epithelial maps reveal epithelial nonuniformity and provide a novel
      benchmark for future and comparative studies.

PMID- 24042486
TI  - Penetrating keratoplasty for perforated corneal ulcers under topical anesthesia.
AB  - PURPOSE: To evaluate the structural and functional outcomes of eyes with
      perforated corneal ulcers undergoing penetrating keratoplasty (PKP) under topical
      anesthesia. METHODS: A prospective analysis of 17 consecutive cases that
      underwent PKP under topical anesthesia, where infiltrative anesthesia was
      contraindicated or general anesthesia could not be given for medical reasons or
      was not available for logistical reasons. RESULTS: Seventeen eyes of 15 patients
      with a mean age of 47.3 +/- 16.2 years underwent a PKP for treating perforated
      corneal ulcers under topical anesthesia. Perforation involved the pupillary zone
      in 13 (76.5%) cases. Preoperatively, 8 patients (47.1%) were phakic, 8 (47.1%)
      were pseudophakic, and 1 (5.9%) was aphakic. The PKP was completed successfully
      in all the eyes. An anterior capsular tear occurred in 3 eyes (17.6%). A
      posterior chamber intraocular implant was put in 1 eye, and 2 eyes were found to
      be aphakic. The patients reported mild to moderate discomfort and tolerated the
      procedure well. At the final follow-up, 10 patients had clear grafts (58.8%), and
      7 patients (41.2%) had partially clear grafts. The best-corrected visual acuity
      was better than 6/18 in 10 eyes and between 6/60 and 6/24 in 7 eyes. CONCLUSIONS:
      PKP can be performed successfully under topical anesthesia in cooperative
      patients who have perforated corneal ulcers.

PMID- 24042487
TI  - [Tethered tape or the fourth factor. A new cause of recurrent stress incontinence
      after midurethral tape procedures vaginal tape insertion].
AB  - BACKGROUND: This is the first report of a newly identified cause of recurrent
      stress urinary incontinence (SUI) after midurethral tape insertion. PATIENTS AND
      METHODS: This article reports a series of cases with primary or secondary tape
      failure including clinical presentation and findings, the results of pelvic floor
      (PF) ultrasound, and the (surgical) correction of malpositioned vaginal tapes.
      RESULTS: A vaginal tape for treating SUI must be accurately placed under the mid
      third of the urethra and at a distance of 3-5 mm from the urethra. Alignment
      parallel to the urethra in the urethrovaginal septum is also essential for
      adequate function. A tethered tape refers to the adhesion of a tape edge to the
      anterior vaginal wall either during primary wound closure or due to secondary
      ingrowths and is typically associated with recurrent SUI during activities or
      changes in posture. Less common is SUI through an increase in pressure from
      cranially, which occurs when coughing or laughing. "Vaginal polyps" may point to
      imminent vaginal erosion of the tape. In the sagittal plane, the PF examination
      will identify an oblique orientation of the tape at rest, an abnormal closeness
      of the tape to the transducer, and changes in tape shape upon manipulation of the
      vaginal probe. Once the diagnosis has been established, a tethered tape is easy
      to correct by realignment or tightening to accomplish correct positioning
      parallel to the urethra. This measure restores tape function and continence.
      CONCLUSION: Primary or secondary failure of a tension-free vaginal tape may be
      caused by a tethered tape. This complication can be diagnosed on the basis of
      characteristic findings at PF ultrasound. In most women, the tape position can be
      corrected and there is no need for tape removal.

PMID- 24042488
TI  - [Acute urinary retention in children: initial manifestation of caudal regression
      syndrome].
AB  - Caudal regression syndrome is a rare and sporadic congenital developmental defect
      of the lower spinal segments and the neural tube. Movement disorders and sensory
      neurological deficits of the lower extremities in conjunction with impaired
      bladder and bowel control are the major symptoms. Abnormal visual aspects of the
      sacral region in combination with maternal gestational diabetes are further
      diagnostic indications. This article reports the unusual case of a toddler
      presenting with acute urinary retention as the initial symptom of caudal
      regression syndrome. 

PMID- 24042489
TI  - [Rehabilitation of erectile function after nerve-sparing radical prostatectomy:
      therapeutic concepts in Germany].
AB  - OBJECTIVE: Despite objective published data regarding rehabilitation of erectile
      function (EF) after nerve-sparing radical prostatectomy (nsRP) the gold-standard
      treatment is still under debate. The aim of this study was to evaluate the
      distribution of the different treatment options in Germany. PATIENTS AND METHODS:
      Between October 2010 and May 2012 a questionnaire was sent to urologists in
      outpatient, general and university hospitals and rehabilitation hospitals in
      Germany. The survey consisted of various questions concerning, e.g. if and what
      kind of therapy urologists choose to support rehabilitation of EF after nsRP.
      Further questions dealt with the frequency, duration and optimal start of the
      chosen therapy. RESULTS: Currently 188 urologists have completed and returned the
      questionnaire. The distribution was urologists in hospitals n=79 and
      outpatient/ambulatory n=106, with 24 % performing surgical treatment and
      urologists in rehabilitation hospitals n=3. The question about the rehabilitation
      concept showed 39 different forms of treatment within this group. To increase EF
      after nsRP PDE5 inhibitors were mostly administered (88 %) with 45 % on request
      compared to 55 %on a daily or regular basis >= 3 times/week. The use of penile
      injection therapy, medicated urethral system for erection (MUSE) and vacuum
      constriction devices (VCD) was prescribed by 32 %, 6 % and 30 % of urologists,
      respectively. Only 14 % of the urologists did not choose any active kind of
      rehabilitation treatment for EF recovery after nsRP. CONCLUSION: Many different
      therapeutic concepts are currently performed in Germany to increase EF recovery
      after nsRP. The use of PDE5 inhibitors is the most commonly chosen treatment
      option. Despite published data regarding effectiveness, the optimal treatment
      seems to be still unknown.

PMID- 24042491
TI  - Incidence of dementia with Lewy bodies and Parkinson disease dementia.
AB  - IMPORTANCE: Epidemiologic data on dementia with Lewy bodies (DLB) and Parkinson
      disease dementia (PDD) remain limited in the United States and worldwide. These
      data are essential to guide research and clinical or public health interventions.
      OBJECTIVE: To investigate the incidence of DLB among residents of Olmsted County,
      Minnesota, and compare it with the incidence of PDD. DESIGN: The medical records
      linkage system of the Rochester Epidemiology Project was used to identify all
      persons who developed parkinsonism and, in particular, DLB or PDD from 1991
      through 2005 (15 years). A movement disorders specialist reviewed the complete
      medical records of each suspected patient to confirm the diagnosis. SETTING:
      Olmsted County, Minnesota, from 1991 through 2005 (15 years). PARTICIPANTS: All
      the residents of Olmsted County, Minnesota, who gave authorization for medical
      record research. MAIN OUTCOMES AND MEASURES: Incidence of DLB and PDD. RESULTS:
      Among 542 incident cases of parkinsonism, 64 had DLB and 46 had PDD. The
      incidence rate of DLB was 3.5 per 100,000 person-years overall, and it increased
      steeply with age. The incidence of PDD was 2.5 overall and also increased steeply
      with age. The incidence rate of DLB and PDD combined was 5.9. Patients with DLB
      were younger at onset of symptoms than patients with PDD and had more
      hallucinations and cognitive fluctuations. Men had a higher incidence of DLB than
      women across the age spectrum. The pathology was consistent with the clinical
      diagnosis in 24 of 31 patients (77.4%) who underwent autopsy. CONCLUSIONS AND
      RELEVANCE: The overall incidence rate of DLB is lower than the rate of Parkinson
      disease. The incidence of DLB increases steeply with age and is markedly higher
      in men. This men to women difference may suggest different etiologic mechanisms.
      Our findings may guide health care planning and prompt new studies.

PMID- 24042492
TI  - Hospital-based surveillance and analysis of genotype variation in Nicaragua after
      the introduction of the pentavalent rotavirus vaccine.
AB  - BACKGROUND: A live, attenuated, pentavalent rotavirus vaccine (RV5) was
      introduced in Nicaragua in 2006 through a 3-year partnership between Merck & Co,
      Inc., and the Nicaraguan Ministry of Health. Nicaragua was the first developing
      nation to include rotavirus vaccine in its national childhood vaccine program. To
      monitor the possibility of changing circulating rotavirus strains after the
      introduction of RV5, we determined the genotypes responsible for rotavirus
      gastroenteritis-related hospitalization during the first 3 postvaccine years.
      METHODS: Stool samples were collected from children with acute gastroenteritis
      who presented to any of 6 participating hospitals within 7-14 days of symptom
      onset. Samples positive for rotavirus antigen were analyzed for P and G genotypes
      using a reverse transcription polymerase chain reaction method. RESULTS: Overall,
      the predominant strains were G2P[4] (41.5%), G1P[8] (40.6%), G4P[8] (5.1%) and
      G3P[8] (4.7%). Strain predominance varied by season. During the 2007 season,
      G4P[8] (53.2%) and G2P[4] (40.5%) predominated. In the 2008 season, G2P[4]
      (77.9%) and G1P[8] (12.6%) were predominant, while in the 2009 season, G1P[8]
      (79.3%) and G3P[8] (7.8%) were predominant. CONCLUSION: No new or unexpected
      strains were predominant in the years immediately following the introduction of
      RV5 into Nicaragua. RV5 does not appear to have substantially altered the
      historical pattern of seasonal fluctuation in rotavirus genotypes.

PMID- 24042493
TI  - An outbreak of Mycobacterium abscessus infection in a Pediatric Intensive Care
      Unit in Kuwait.
AB  - BACKGROUND: Mycobacterium abscessus has been associated with respiratory tract
      infections, localized skin and soft tissue infections and sepsis. However,
      outbreaks of M. abscessus are rare. AIM: to report an outbreak of M. abscessus
      causing respiratory tract infections in a Pediatric Intensive Care Unit (PICU) in
      Kuwait, its investigation and control measures. METHODS: Respiratory secretions
      were obtained from ventilator-dependent patients showing signs of sepsis,
      including fever, malaise and weight loss. The specimens were cultured on
      appropriate routine media. After the results of the sample taken from the index
      case as acid-fast bacilli positive, all patients were screened for M. abscessus
      carriage. Isolates were identified by INNO-LiPA Mycobacteria v2 line probe assay
      and DNA sequencing. Molecular fingerprinting DiversiLab strain typing was
      performed on the isolates. Epidemiologic investigation was conducted during the
      outbreak. FINDINGS: the outbreak affected 5 patients, 4 of whom had severe
      infections including 1 patient with septicemia. Asymptomatic carriage of outbreak
      strain was found in 1 patient. All environmental samples were negative for M.
      abscessus but some were positive for M. gordonae and M. fortuitum. The source
      could not be identified. Stringent infection control measures were put in place,
      including reemphasizing hand hygiene and closure of the Pediatric Intensive Care
      Unit to new admissions. A year later, no further case has occurred after the last
      case. CONCLUSION: To our knowledge, this is the first report of a hospital
      acquired outbreak of respiratory tract infection caused by M. abscessus in a
      Pediatric Intensive Care Unit. In the absence of definite source identification,
      reinforcement of standard infection control guidelines was successful in
      containing the outbreak.

PMID- 24042494
TI  - A biosynthetic pathway of sesquiterpene lactones in Smallanthus sonchifolius and
      their localization in leaf tissues by MALDI imaging.
AB  - The biosynthetic route for epoxyangelate esters of the sesquiterpene lactones
      (STL) uvedalin and enhydrin from in vitro cultures of Smallanthus sonchifolius
      (Asteraceae) was investigated with (13)C-precursors for the first time in the
      literature. Photomicroscope analyses and studies using MALDI-MS imaging confirmed
      that glandular trichomes accumulate STL. 

PMID- 24042495
TI  - Effects of icariin on the alkline phosphatase activity of human periodontal
      ligament cells inhibited by lipopolysaccharide.
AB  - Icariin (ICA), a flavanoid isolated from herbal Epimedium, has multiple
      biological activities. The present study investigated the effects of ICA on the
      proliferation and alkaline phosphatase (ALP) activity (an index for PDLC
      differentiation) of human periodontal ligament cells (hPDLCs) inhibited by
      lipopolysaccharide (LPS). hPDLCs were cultured in vitro and stimulated with
      various concentrations of ICA. The proliferation ability of hPDLCs was detected
      by an MTT assay. The activity of ALP was determined by the p-Nitrophenyl
      phosphate method, and the expression of ALP was analyzed by reverse transcription
      polymerase chain reaction and western blot analysis. ICA exhibited a dose
      dependent effect on the proliferation of hPDLCs in a suitable concentration
      range, from 10-6 to 10-8 mol/l, and with a mediate optimal concentration (10-6
      mol/l). The alkaline phosphatase activity was markedly inhibited in 10 ug/ml LPS
      treated PDLCs and this inhibition was suppressed in the presence of icariin at a
      concentration of 10-6 mol/L following prolonged treatment (96 h). Therefore, this
      study provided insight into the use of ICA for periapical tissue regeneration.

PMID- 24042496
TI  - Inner retinal inhibition shapes the receptive field of retinal ganglion cells in
      primate.
AB  - The centre-surround organisation of receptive fields is a feature of most retinal
      ganglion cells (RGCs) and is critical for spatial discrimination and contrast
      detection. Although lateral inhibitory processes are known to be important in
      generating the receptive field surround, the contribution of each of the two
      synaptic layers in the primate retina remains unclear. Here we studied the
      spatial organisation of excitatory and inhibitory synaptic inputs onto ON and OFF
      ganglion cells in the primate retina. All RGCs showed an increase in excitation
      in response to stimulus of preferred polarity. Inhibition onto RGCs comprised two
      types of responses to preferred polarity: some RGCs showed an increase in
      inhibition whilst others showed removal of tonic inhibition. Excitatory inputs
      were strongly spatially tuned but inhibitory inputs showed more variable
      organisation: in some neurons they were as strongly tuned as excitation, and in
      others inhibitory inputs showed no spatial tuning. We targeted one source of
      inner retinal inhibition by functionally ablating spiking amacrine cells with
      bath application of tetrodotoxin (TTX). TTX significantly reduced the spatial
      tuning of excitatory inputs. In addition, TTX reduced inhibition onto those RGCs
      where a stimulus of preferred polarity increased inhibition. Reconstruction of
      the spatial tuning properties by somatic injection of excitatory and inhibitory
      synaptic conductances verified that TTX-mediated inhibition onto bipolar cells
      increases the strength of the surround in RGC spiking output. These results
      indicate that in the primate retina inhibitory mechanisms in the inner plexiform
      layer sharpen the spatial tuning of ganglion cells.

PMID- 24042497
TI  - The emergence of subcellular pacemaker sites for calcium waves and oscillations.
AB  - Calcium (Ca(2+)) waves generating oscillatory Ca(2+) signals are widely observed
      in biological cells. Experimental studies have shown that under certain
      conditions, initiation of Ca(2+) waves is random in space and time, while under
      other conditions, waves occur repetitively from preferred locations (pacemaker
      sites) from which they entrain the whole cell. In this study, we use computer
      simulations to investigate the self-organization of Ca(2+) sparks into pacemaker
      sites generating Ca(2+) oscillations. In both ventricular myocyte experiments and
      computer simulations of a heterogeneous Ca(2+) release unit (CRU) network model,
      we show that Ca(2+) waves occur randomly in space and time when the Ca(2+) level
      is low, but as the Ca(2+) level increases, waves occur repetitively from the same
      sites. Our analysis indicates that this transition to entrainment can be
      attributed to the fact that random Ca(2+) sparks self-organize into Ca(2+)
      oscillations differently at low and high Ca(2+) levels. At low Ca(2+), the whole
      cell Ca(2+) oscillation frequency of the coupled CRU system is much slower than
      that of an isolated single CRU. Compared to a single CRU, the distribution of
      interspike intervals (ISIs) of the coupled CRU network exhibits a greater
      variation, and its ISI distribution is asymmetric with respect to the peak,
      exhibiting a fat tail. At high Ca(2+), however, the coupled CRU network has a
      faster frequency and lesser ISI variation compared to an individual CRU. The ISI
      distribution of the coupled network no longer exhibits a fat tail and is well
      approximated by a Gaussian distribution. This same Ca(2+) oscillation behaviour
      can also be achieved by varying the number of ryanodine receptors per CRU or the
      distance between CRUs. Using these results, we develop a theory for the
      entrainment of random oscillators which provides a unified explanation for the
      experimental observations underlying the emergence of pacemaker sites and Ca(2+)
      oscillations.

PMID- 24042498
TI  - The lateral reticular nucleus: a precerebellar centre providing the cerebellum
      with overview and integration of motor functions at systems level. A new
      hypothesis.
AB  - The lateral reticular nucleus (LRN) is a major precerebellar centre of mossy
      fibre information to the cerebellum from the spinal cord that is distinct from
      the direct spinocerebellar paths. The LRN has traditionally been considered to
      provide the cerebellum with segregated information from several spinal systems
      controlling posture, reaching, grasping, locomotion, scratching and respiration.
      However, results are presented that show extensive convergence on a majority of
      LRN neurons from spinal systems. We propose a new hypothesis suggesting that the
      LRN may use extensive convergence from the different input systems to provide
      overview and integration of linked motor components to the cerebellum. This
      integrated information is sent in parallel with the segregated information from
      the individual systems to the cerebellum that finally may compare the activity
      and make necessary adjustments of various motor behaviours.

PMID- 24042499
TI  - Modulation of the autonomic nervous system and behaviour by acute glial cell Gq
      protein-coupled receptor activation in vivo.
AB  - Glial fibrillary acidic protein (GFAP)-expressing cells (GFAP(+) glial cells) are
      the predominant cell type in the central and peripheral nervous systems. Our
      understanding of the role of GFAP(+) glial cells and their signalling systems in
      vivo is limited due to our inability to manipulate these cells and their
      receptors in a cell type-specific and non-invasive manner. To circumvent this
      limitation, we developed a transgenic mouse line (GFAP-hM3Dq mice) that expresses
      an engineered Gq protein-coupled receptor (Gq-GPCR) known as hM3Dq DREADD
      (designer receptor exclusively activated by designer drug) selectively in GFAP(+)
      glial cells. The hM3Dq receptor is activated solely by a pharmacologically inert,
      but bioavailable, ligand (clozapine-N-oxide; CNO), while being non-responsive to
      endogenous GPCR ligands. In GFAP-hM3Dq mice, CNO administration increased heart
      rate, blood pressure and saliva formation, as well as decreased body temperature,
      parameters that are controlled by the autonomic nervous system (ANS).
      Additionally, changes in activity-related behaviour and motor coordination were
      observed following CNO administration. Genetically blocking inositol 1,4,5
      trisphosphate (IP3)-dependent Ca(2+) increases in astrocytes failed to interfere
      with CNO-mediated changes in ANS function, locomotor activity or motor
      coordination. Our findings reveal an unexpectedly broad role of GFAP(+) glial
      cells in modulating complex physiology and behaviour in vivo and suggest that
      these effects are not dependent on IP3-dependent increases in astrocytic Ca(2+). 

PMID- 24042500
TI  - Mechanisms contributing to cluster formation in the inferior olivary nucleus in
      brainstem slices from postnatal mice.
AB  - The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5
      P15.5) spontaneously generates clusters of neurons with synchronous calcium
      transients, and intracellular recordings from IO neurons suggest that electrical
      coupling between neighbouring IO neurons may serve as a synchronizing mechanism.
      Here, we studied the cluster-forming mechanism and find that clusters overlap
      extensively with an overlap distribution that resembles the distribution for a
      random overlap model. The average somatodendritic field size of single curly IO
      neurons was ~6400 MUm(2), which is slightly smaller than the average IO cluster
      size. Eighty-seven neurons with overlapping dendrites were estimated to be
      contained in the principal olive mean cluster size, and about six non-overlapping
      curly IO neurons could be contained within the largest clusters. Clusters could
      also be induced by iontophoresis with glutamate. Induced clusters were inhibited
      by tetrodotoxin, carbenoxelone and 18beta-glycyrrhetinic acid, suggesting that
      sodium action potentials and electrical coupling are involved in glutamate
      induced cluster formation, which could also be induced by activation of N-methyl
      d-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      receptors. Spikelets and a small transient depolarizing response were observed
      during glutamate-induced cluster formation. Calcium transients spread with
      decreasing velocity during cluster formation, and somatic action potentials and
      cluster formation are accompanied by large dendritic calcium transients. In
      conclusion, cluster formation depends on gap junctions, sodium action potentials
      and spontaneous clusters occur randomly throughout the IO. The relative slow
      signal spread during cluster formation, combined with a strong dendritic influx
      of calcium, may signify that active dendritic properties contribute to cluster
      formation.

PMID- 24042501
TI  - Redox modification of ryanodine receptors by mitochondria-derived reactive oxygen
      species contributes to aberrant Ca2+ handling in ageing rabbit hearts.
AB  - Ageing is associated with a blunted response to sympathetic stimulation and an
      increased risk of arrhythmia and sudden cardiac death. Aberrant calcium (Ca(2+))
      handling is an important contributor to the electrical and contractile
      dysfunction associated with ageing. Yet, the specific molecular mechanisms
      underlying abnormal Ca(2+) handling in ageing heart remain poorly understood. In
      this study, we used ventricular myocytes isolated from young (5-9 months) and old
      (4-6 years) rabbit hearts to test the hypothesis that changes in Ca(2+)
      homeostasis are caused by post-translational modification of ryanodine receptors
      (RyRs) by mitochondria-derived reactive oxygen species (ROS) generated in the
      ageing heart. Changes in parameters of Ca(2+) handling were determined by
      measuring cytosolic and intra-sarcoplasmic reticulum (SR) Ca(2+) dynamics in
      intact and permeabilized ventricular myocytes using confocal microscopy. We also
      measured age-related changes in ROS production and mitochondria membrane
      potential using a ROS-sensitive dye and a mitochondrial voltage-sensitive
      fluorescent indicator, respectively. In permeablized myocytes, ageing did not
      change SERCA activity and spark frequency but decreased spark amplitude and SR
      Ca(2+) load suggesting increased RyR activity. Treatment with the antioxidant
      dithiothreitol reduced RyR-mediated SR Ca(2+) leak in permeabilized myocytes from
      old rabbit hearts to the level comparable to young. Moreover, myocytes from old
      rabbits had more depolarized mitochondria membrane potential and increased rate
      of ROS production. Under beta-adrenergic stimulation, Ca(2+) transient amplitude,
      SR Ca(2+) load, and latency of pro-arrhythmic spontaneous Ca(2+) waves (SCWs)
      were decreased while RyR-mediated SR Ca(2+) leak was increased in cardiomyocytes
      from old rabbits. Additionally, with beta-adrenergic stimulation, scavenging of
      mitochondrial ROS in myocytes from old rabbit hearts restored redox status of
      RyRs, which reduced SR Ca(2+) leak, ablated most SCWs, and increased latency to
      levels comparable to young. These data indicate that an age-associated increase
      of ROS production by mitochondria leads to the thiol-oxidation of RyRs, which
      underlies the hyperactivity of RyRs and thereby shortened refractoriness of
      Ca(2+) release in cardiomyocytes from the ageing heart. This mechanism probably
      plays an important role in the increased incidence of arrhythmia and sudden death
      in the ageing population.

PMID- 24042502
TI  - Oxygen and mitochondrial inhibitors modulate both monomeric and heteromeric TASK
      1 and TASK-3 channels in mouse carotid body type-1 cells.
AB  - In rat arterial chemoreceptors, background potassium channels play an important
      role in maintaining resting membrane potential and promoting depolarization and
      excitation in response to hypoxia or acidosis. It has been suggested that these
      channels are a heterodimer of TASK-1 and TASK-3 based on their similarity to
      heterologously expressed TASK-1/3 fusion proteins. In this study, we sought to
      confirm the identity of these channels through germline ablation of Task-1
      (Kcnk3) and Task-3 (Kcnk9) in mice. Background K-channels were abundant in
      carotid body type-1 cells from wild-type mice and comparable to those previously
      described in rat type-1 cells with a main conductance state of 33 pS. This
      channel was absent from both Task-1(-/-) and Task-3(-/-) cells. In its place we
      observed a larger (38 pS) K(+)-channel in Task-1(-/-) cells and a smaller (18 pS)
      K(+)-channel in Task-3(-/-) cells. None of these channels were observed in Task
      1(-/-)/Task-3(-/-) double knock-out mice. We therefore conclude that the
      predominant background K-channel in wild-type mice is a TASK-1/TASK-3
      heterodimer, whereas that in Task-1(-/-) mice is TASK-3 and, conversely, that in
      Task-3(-/-) mice is TASK-1. All three forms of TASK channel in type-1 cells were
      inhibited by hypoxia, cyanide and the uncoupler FCCP, but the greatest
      sensitivity was seen in TASK-1 and TASK-1/TASK-3 channels. In summary, the
      background K-channel in type-1 cells is predominantly a TASK-1/TASK-3
      heterodimer. Although both TASK-1 and TASK-3 are able to couple to the oxygen and
      metabolism sensing pathways present in type-1 cells, channels containing TASK-1
      appear to be more sensitive.

PMID- 24042503
TI  - Respiratory, metabolic and cardiac functions are altered by disinhibition of
      subregions of the medial prefrontal cortex.
AB  - The prefrontal cortex (PFC) is referred to as the visceral motor cortex; however,
      little is known about whether this region influences respiratory or metabolic
      outflows. The aim of this study was to describe simultaneous changes in
      respiratory, metabolic and cardiovascular functions evoked by disinhibition of
      the medial PFC (mPFC) and adjacent lateral septal nucleus (LSN). In urethane
      anaesthetized rats, bicuculline methiodide was microinjected (2 mm; GABA-A
      receptor antagonist) into 90 sites in the mPFC at 0.72-4.00 mm from bregma.
      Phrenic nerve amplitude and frequency, arterial pressure, heart rate, splanchnic
      and lumbar sympathetic nerve activities (SNA), expired CO2, and core and brown
      adipose tissue temperatures were measured. Novel findings included disturbances
      to respiratory rhythm evoked from all subregions of the mPFC. Injections into the
      cingulate cortex evoked reductions in central respiratory function exclusively,
      whereas in ventral sites, particularly the infralimbic region, increases in
      respiratory drive and frequency, and metabolic and cardiac outflows were evoked.
      Disinhibition of sites in surrounding regions revealed that the LSN could evoke
      cardiovascular changes accompanied by distinct oscillations in SNA, as well as
      increases in respiratory amplitude. We show that activation of neurons within the
      mPFC and LSN influence respiratory, metabolic and cardiac outflows in a site
      dependent manner. This study has implications with respect to the altered PFC
      neuronal activity seen in stress-related and mental health disorders, and
      suggests how basic physiological systems may be affected.

PMID- 24042505
TI  - Assembly of a multilayer film and catalytic application in Suzuki cross-coupling
      reaction based on synergistic effects of a conjugated organometallic pyridyl
      Pt(C=C)2 moiety with palladium.
AB  - A multilayer film (Pd(2+)/1)n was prepared with Pd(II) ions and platinum compound
      trans-[Pt(PPh3)2(C=CPy)2] (1) using the layer-by-layer self-assembly method. The
      film loaded on the quartz slide could be capable of discharging high catalytic
      active Pd species to promote the C-C coupling reaction, with extraordinarily low
      Pd-loading (6.6 * 10(-6) mol%) and high catalytic efficiency in H2O-EtOH
      solution.

PMID- 24042504
TI  - Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity
      in trained OPA1-deficient mice.
AB  - The role of OPA1, a GTPase dynamin protein mainly involved in the fusion of inner
      mitochondrial membranes, has been studied in many cell types, but only a few
      studies have been conducted on adult differentiated tissues such as cardiac or
      skeletal muscle cells. Yet OPA1 is highly expressed in these cells, and could
      play different roles, especially in response to an environmental stress like
      exercise. Endurance exercise increases energy demand in skeletal muscle and
      repeated activity induces mitochondrial biogenesis and activation of fusion
      fission cycles for the synthesis of new mitochondria. But currently no study has
      clearly shown a link between mitochondrial dynamics and biogenesis. Using a mouse
      model of haploinsufficiency for the Opa1 gene (Opa1(+/-)), we therefore studied
      the impact of OPA1 deficiency on the adaptation ability of fast skeletal muscles
      to endurance exercise training. Our results show that, surprisingly, Opa1(+/-)
      mice were able to perform the same physical activity as control mice. However,
      the adaptation strategies of both strains after training differed: while in
      control mice mitochondrial biogenesis was increased as expected, in Opa1(+/-)
      mice this process was blunted. Instead, training in Opa1(+/-) mice led to an
      increase in endurance capacity, and a specific adaptive response involving a
      metabolic remodelling towards enhanced fatty acid utilization. In conclusion,
      OPA1 appears necessary for the normal adaptive response and mitochondrial
      biogenesis of skeletal muscle to training. This work opens new perspectives on
      the role of mitochondrial dynamics in skeletal muscle cells and during adaptation
      to stress.

PMID- 24042506
TI  - Facile synthesis of carbon nanotube-inorganic hybrid materials with improved
      photoactivity.
AB  - A facile method was used for the synthesis of CNTs@TiO2 nanocomposites using a
      simple apparatus at ambient pressure and temperature. CNTs@TiO2 exhibit core
      shell structure without any interfacial adhesive layer on the CNT surface. The
      photodegradation of methyl orange suggests enhanced photoactivity of CNTs@TiO2
      under UV light. The morphology, structure and composition of CNTs@TiO2 were also
      investigated. 

PMID- 24042507
TI  - Reversibility of the pulmonary function based on the partial flow-volume curve
      predicts the efficacy of bronchodilator therapy for treating chronic cough.
AB  - OBJECTIVE: Partial expiratory flow-volume curves have the potential to detect
      mild bronchoconstriction because they are not affected by the modulatory effects
      of deep inspiration. The aim of this study was to investigate the relationship
      between the efficacy of bronchodilator therapy (BDT) in treating the cough and to
      assess the increase in the expiratory flow of the partial flow-volume curve at
      40% above the residual volume level (PEF40) caused by treatment with a short
      acting beta-2 agonist (SABA) in patients with chronic nonproductive cough.
      METHODS: We measured the reversibility of PEF40 caused by a SABA in 42 patients
      with chronic nonproductive cough at visit 1 (day 0). The patients received BDT
      for six days. The visual analogue scale (VAS) was used to assess the efficacy of
      BDT in treating coughing at visit 2 (day 7) (0 mm, 'no cough;' 100 mm, 'no change
      in coughing'). RESULTS: Reversibility of the PEF40 was correlated (r=0.690,
      p<0.001) with the VAS score determined at visit 2 and was higher in the patients
      with cough variant asthma (CVA) (44.9 +/- 18.3%) than in those with atopic cough
      (13.4 +/- 10.4%) (p<0.01). CONCLUSION: Reversibility of the PEF40 predicted the
      efficacy of BDT in patients with chronic nonproductive cough and helped to
      identify patients with CVA.

PMID- 24042508
TI  - Clinical characteristics and outcomes of 11 patients with pure red cell aplasia
      at a single institution over a 13-year period.
AB  - OBJECTIVE: Pure red cell aplasia (PRCA) is a rare clinical entity characterized
      by anemia due to severe suppression of erythroid precursors, where the other cell
      lineages in the bone marrow remain morphologically normal. A standard treatment
      has not yet been established for PRCA due to the rarity of this condition.
      Recently, however, the administration of either cyclosporine (CSP) or
      prednisolone (PSL) has been reported to be an effective treatment for PRCA.
      METHODS: To clarify the clinical characteristics of PRCA, 11 PRCA cases were
      retrospectively analyzed over a 13-year period at our institution. Since acute
      PRCA was found to be self-limiting, we administered the immunosuppressive
      treatment of CSP or PSL after providing supportive care for 4 weeks. RESULTS: The
      causes of PRCA were as follows: idiopathic (3), acute parvovirus infection (1),
      chronic parvovirus infection (3), thymic tumor (3), and end-stage renal disease
      with hemodialysis (1). Complete remission (CR) was achieved for 4 of the 5
      patients treated with CSP, for 2 of the 3 patients with chronic parvovirus
      infection treated by immunoglobulin (Ig), and for all 3 patients treated with
      PSL. During the follow-up periods, 4 of the 11 patients relapsed. Complete
      remission was achieved a second time in all 4 cases by therapies that were more
      intensive and had longer administration periods than those provided during
      initial treatment. Consequently, 9 of the 11 patients were still alive (80%)
      after 5 years. CONCLUSION: Depending on the cause of the PRCA, treatment with
      CSP, PSL, or Ig was found to be effective in most PRCA cases.

PMID- 24042509
TI  - MRI neurography findings in patients with idiopathic brachial plexopathy:
      correlations with clinical-neurophysiological data in eight consecutive cases.
AB  - OBJECTIVE: Idiopathic brachial plexopathy is a non-progressive disorder
      characterized by the sudden onset of shoulder pain associated with weakness and
      sometimes paraesthesia of the arm. Clinical and electrophysiological examinations
      are the primary diagnostic tools and allow physicians to localize the site of
      damage. MRI neurography is rarely performed in this setting. METHODS: We herein
      describe the cases of eight consecutive patients suffering from idiopathic
      brachial plexopathy. All patients underwent clinical visits, neurophysiological
      evaluations and MRI neurography. RESULTS: We confirmed the primary role of
      clinical and neurophysiological evaluations in the diagnosis of idiopathic
      brachial plexopathy and demonstrate the usefulness of brachial plexus MRI
      neurography for confirming the presence of inflammatory changes. CONCLUSION: In
      patients with idiopathic brachial plexopathy, MR neurography is a helpful tool
      for excluding different aetiologies, such as compression or tumour formation,
      and/or confirming inflammatory changes.

PMID- 24042510
TI  - Spinal magnetic resonance imaging manifestations at neurological onset in
      Japanese patients with spinal cord sarcoidosis.
AB  - OBJECTIVE: We retrospectively investigated spinal magnetic resonance imaging
      (MRI) manifestations at neurological onset in Japanese patients with spinal cord
      sarcoidosis. METHODS: Between July 2000 and April 2012, we reviewed our database
      and recruited patients with spinal cord sarcoidosis. On spinal MRI performed at
      neurological onset, the following items were evaluated: the vertebral-segment
      distribution and length of intramedullay T2-elongated lesions, abnormal
      enhancement patterns and distributions and the concomitant presence of
      spondylosis and associated extraspinal lesions. If available, brain MRI scans
      were concomitantly assessed. RESULTS: Nine patients were enrolled (four men and
      five women; median, 49 years). Reflecting Japanese epidemiological backgrounds, a
      predilection for occurrence was observed in young men and middle-aged women.
      Intramedullary T2-elongated lesions were present in eight patients, peaking at
      the C5 level, with a mean length of 3.7 +/- 2.6 vertebral segments. Spondylosis
      coexisted in the middle-aged patients. Abnormal intramedullary enhancement with
      concomitantly involved the nerve roots was observed in six patients, comprised of
      two types reflecting the disease progression: linear- and/or nodular enhancement
      along the surface of the spinal cord and intramedullary enhancement consisting of
      patchy, broad-based enhancement adjacent to the cord surface. Five patients had
      associated extraspinal lesions, including lymphadenopathy in four patients and
      brain involvement in four patients. CONCLUSION: Spinal cord sarcoidosis exhibits
      a predilection for young men and middle-aged women among Japanese individuals and
      is characterized by intramedullary T2-elongated lesions spreading more than three
      vertebral segments peaking at the C5 level, two types of abnormal intramedullary
      enhancement reflecting disease progression, frequent nerve root involvement and
      lymphadenopathy.

PMID- 24042511
TI  - Large solid-pseudopapillary neoplasm of the pancreas with aberrant protein
      expression and mutation of beta-catenin: a case report and literature review of
      the distribution of beta-catenin mutation.
AB  - Solid-pseudopapillary neoplasms (SPN) are rare pancreatic tumors. The etiology of
      SPN involves mutations in the gene that encodes beta-catenin (CTNNB1). We herein
      report the case of a 23-year-old woman with a large SPN with proliferating tumor
      cells that displayed both solid and pseudo-papillary patterns. The simultaneous
      nuclear accumulation and loss of membrane localization of beta-catenin and E
      cadherin was specifically observed in the tumor cells. Further, the tumor cells
      were shown to harbor a missense mutation in exon 3 of CTNNB1. We also present a
      review of the literature describing the clustering of CTNNB1 mutations in
      patients with SPN. 

PMID- 24042513
TI  - A resected perivascular epithelioid cell tumor (PEComa) of the pancreas diagnosed
      using endoscopic ultrasound-guided fine-needle aspiration.
AB  - Primary perivascular epithelioid cell tumors (PEComas) of the pancreas are
      extremely rare. We herein report our experience with a patient who had a primary
      PEComa of the pancreas that was diagnosed by the preoperative histopathological
      examination of a biopsy specimen obtained by endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA). The patient was a 43-year-old woman whose chief
      complaint was abdominal pain. Imaging studies revealed a pancreatic tumor.
      Gastrointestinal stromal tumor (GIST), solid pseudopapillary tumor and
      neuroendocrine tumor were considered in the differential diagnosis. A
      histopathological examination of a specimen of the tumor obtained using EUS-FNA
      showed spindle-shaped tumor cells with enlarged nuclei and eosinophilic
      cytoplasm. The tumor cells proliferated in a sheet-like fashion and stained
      positive for the melanoma-associated antigen HMB-45. A PEComa was thus diagnosed.
      If an adequate tumor specimen can be obtained using EUS-FNA, immunostaining may
      facilitate the diagnosis of extremely rare diseases and therefore assist in
      deciding the treatment policy. 

PMID- 24042514
TI  - A rare case of a coronary artery anomaly detected on multidetector computed
      tomography.
AB  - An anomalous aortic origin of the coronary artery arising from the opposite sinus
      with an interarterial course is a rare condition that is associated with a high
      risk of sudden cardiac death during or after strenuous exertion. We herein report
      the case of a 47-year-old woman presenting with chest pain, syncope and
      palpitations who presented with a rare coronary artery anomaly on multidetector
      computed tomography coronary artery (MDCT-CA) with prospective electrocardiogram
      (ECG) gating. 

PMID- 24042512
TI  - A chronic subdural hematoma in a patient receiving combination therapy with
      pegylated interferon alfa-2b and ribavirin for chronic hepatitis C.
AB  - A 70-year-old man who suffered from chronic hepatitis C was infected with HCV
      genotype 1 and exhibited a high viral load. He had hypertension and had consumed
      the equivalent of 50 g of ethanol per day. He was treated with pegylated
      interferon and ribavirin. After 51 weeks, he developed an unsteady gait while
      walking and demonstrated Barre's sign on the right foot and a headache. Contrast
      computed tomography showed a subdural hematoma with a mass effect. The patient
      was treated with drainage and aspiration surgery via a burr hole. Following the
      drainage procedure, there were no neurological sequelae. Treatment with pegylated
      interferon and ribavirin was discontinued. Fortunately, a sustained virological
      response was achieved. 

PMID- 24042515
TI  - Primary aldosteronism with concurrent primary hyperparathyroidism in a patient
      with arrhythmic disorders.
AB  - A 25-year-old Caucasian woman was admitted to our department with severe
      hypokalemia that was associated with hypercalcemia. An endocrinological
      investigation showed the coexistence of primary hyperparathyroidism (PHPT) and
      primary aldosteronism (PA), arising from an adenoma of the left cortical adrenal
      gland. The patient underwent left laparoscopic adrenalectomy, but refused the
      surgical neck exploration that would be required for parathyroidectomy. The post
      operative course was uneventful, and the patient realized a normalization of her
      potassium serum level and a reduction of her blood pressure values. We herein
      report the important issues regarding the management of a severe electrolyte
      imbalance, in view of the reciprocal interaction between aldosterone and
      parathyroid hormone, and their combined potential for causing cardiovascular
      damage. 

PMID- 24042516
TI  - Extrapyramidal symptoms and advanced calcification of the basal ganglia in a
      patient with autosomal dominant hypocalcemia.
AB  - Most cases of hypoparathyroidism with decreased parathyroid hormone (PTH)
      secretion, excluding secondary hypoparathyroidism, are considered to be
      idiopathic. We herein report a relatively rare case of hypoparathyroidism with
      extrapyramidal symptoms, including brachybasia and a frozen gait, caused by
      advanced basal ganglia calcification in a 64-year-old man with
      hypoparathyroidism. A DNA (deoxyribonucleic acid) analysis of blood samples
      obtained from the patient and his eldest daughter revealed autosomal dominant
      hypocalcemia (ADH) with mutations in the calcium-sensing receptor (CaSR) gene. In
      cases of chronic hypoparathyroidism, calcification of the basal ganglia is
      observed if the patient is not treated for a long period. However, extrapyramidal
      symptoms as a complication of hypoparathyroidism are relatively rare. 

PMID- 24042517
TI  - Flank pain, nausea, vomiting and hypotension in a chronic hemodialysis patient
      with a spontaneous perirenal hemorrhage.
AB  - Decreases in blood pressure develop in response to a wide range of clinical
      disorders. Various factors have been implicated in the development of
      hemodialysis-associated hypotension, including an impairment of the compensatory
      processes, an autonomic dysfunction or cardiac failure. The additional presence
      of concomitant acute abdomen may result in a diagnostically challenging
      situation. We herein report our experience with a chronic hemodialysis patient
      who developed severe hypotension with acute flank pain due to spontaneous
      bleeding around the kidney. Concerns regarding the management of the disease are
      also discussed. 

PMID- 24042518
TI  - Acute post-streptococcal glomerulonephritis with acute kidney injury in nephrotic
      syndrome with the glomerular deposition of nephritis-associated plasmin receptor
      antigen.
AB  - We herein report the case of a 17-year-old man who developed an increased plasma
      creatinine level (11.1 mg/dL) and oliguria with massive proteinuria (27.3 g/day)
      four weeks after an abraded wound to his right knee. The histology of the renal
      biopsy specimens showed diffuse endocapillary proliferative glomerulonephritis
      with the deposition of nephritis-associated plasmin receptor in the glomerulus. A
      case of acute kidney injury due to nephrotic syndrome caused by acute post
      streptococcal glomerulonephritis was diagnosed. His renal function and
      proteinuria were improved with supportive care, including hemodialysis, without
      the administration of immunosuppressive agents. 

PMID- 24042519
TI  - Wernicke's encephalopathy that developed during the introduction period of
      peritoneal dialysis.
AB  - A 43-year-old man was admitted with end-stage renal disease caused by IgA
      nephropathy, and was treated with maintenance peritoneal dialysis. The patient
      developed general fatigue and appetite loss, and his symptoms were gradually
      aggravated by depression. After approximately 2 months on dialysis, the patient
      presented with altered consciousness and ophthalmoplegia. Wernicke's
      encephalopathy was diagnosed based on the presence of classic symptoms and the
      findings on magnetic resonance imaging. Thiamine replacement therapy was
      immediately initiated. The patient recovered from most of his neurological
      symptoms; however, the sequela of Korsakoff syndrome remained. A marginal
      thiamine deficiency in combination with predisposing factors must be considered
      when treating dialysis patients. 

PMID- 24042520
TI  - Thrombotic microangiopathy secondary to steroid pulse therapy administered for
      refractory nephrotic syndrome.
AB  - A 79-year-old woman with familial hyperlipidemia was treated with low-density
      lipoprotein apheresis. She was hospitalized due to fatigue and edema, and massive
      proteinuria was discovered. Renal biopsy revealed no distinct abnormalities, thus
      suggesting a diagnosis of minimal change nephrotic syndrome. She developed acute
      kidney injury and hemodialysis was initiated. Two series of steroid pulse therapy
      were given, but the proteinuria did not decrease. Thereafter, she developed
      thrombocytopenia and fell into a stupor. Thrombotic microangiopathy (TMA) was the
      most likely diagnosis. Plasma exchange was initiated, resulting in improvements
      in platelet counts and in her level of consciousness. Clinicians should therefore
      be aware that TMA can occur as a result of steroid pulse therapy. 

PMID- 24042521
TI  - Immunoglobulin G4-related lung disease accompanied by organizing pneumonia.
AB  - The full picture of immunoglobulin G4-related lung disease (IgG4-RLD) has not yet
      been elucidated. A 69-year-old man was referred to us with a more than 2-week
      history of productive cough and fatigue. Chest CT showed an airspace
      consolidation along the bronchovascular bundles. The pathological findings that
      were obtained from an open-lung biopsy showed both organizing pneumonia and
      interstitial pneumonia. Based on the established, comprehensive diagnostic
      criteria for IgG4-related disease (RD) as of 2011, this patient was given a
      definitive diagnosis of IgG4-RD. A further accumulation and analysis of those
      cases that concomitantly present with both IgG4-RLD and organizing pneumonia,
      like our patient, may contribute to the elucidation of the pathology of IgG4-RLD
      and the establishment of the disease spectrum. 

PMID- 24042522
TI  - Solitary extramedullary plasmacytoma presenting as an endobronchial mass.
AB  - Solitary extramedullary plasmacytoma (SEP) is a plasma cell neoplasm that
      develops outside of the bone marrow. A solitary, exophytic growth in the airway
      is an extremely rare presentation of SEP. We herein report a case of SEP
      presenting as an endobronchial mass. The tumor was treated by rigid bronchoscopic
      debulking followed by ablation using argon plasma coagulation. However, the tumor
      could not be completely removed due to its wide base. Adjuvant radiotherapy was
      administered as the curative therapy. A biopsy was performed on the resected
      specimen and the diagnosis of plasmacytoma was thereby confirmed. 

PMID- 24042523
TI  - An autopsy case of pulmonary aspergillosis with fungus ball formation in an
      artificial aortic graft.
AB  - A 38-year-old man with Marfan syndrome underwent an aortic replacement with an
      artificial aortic valve at 27 years of age and an aortic graft at 31 years of
      age. In 2011, he was diagnosed as having chronic necrotizing pulmonary
      aspergillosis (CNPA). He developed a fever and an increased sputum volume and was
      admitted to the hospital in 2012. Contrast-enhanced CT showed an irregularly
      shaped nonenhanced structure in the aortic graft. He died on hospital day 31.
      From the autopsy findings, we speculated that an infiltration by the CNPA lesion
      into a pulmonary vein was followed by the hematogenous formation of a fungus ball
      in the aortic graft. 

PMID- 24042524
TI  - Adult-onset Huntington's disease that presented without chorea.
AB  - We herein report a case of late-onset Huntington's disease (HD) that presented
      without any involuntary movement. The patient was in her forties at onset, and
      she lacked any rigidity; thus, the HD in this case was completely different than
      the Westphal variant. The diagnosis was made by confirming the expansion of CAG
      repeats in the HD gene after obtaining information about her sister's clinical
      features, since her sister presented with typical HD. In late onset HD,
      involuntary movement is thought to be the core feature; therefore, the clinical
      features of this case are considered to be unique and noteworthy. 

PMID- 24042525
TI  - Use of ramelteon for the treatment of secondary REM sleep behavior disorder.
AB  - We used ramelteon to treat two patients with secondary REM sleep behavior
      disorder (RBD) complications along with neurodegenerative diseases including
      multiple system atrophy and Parkinson's disease. These two patients not only
      improved in terms of their clinical RBD symptoms but also exhibited a decrease in
      the proportion of REM sleep without atonia (from 8.5% to 3.5% and from 10.9% to
      3.9% in the two patients). Although clonazepam is the standard first-line therapy
      for the treatment of RBD, ramelteon might be an effective treatment alternative
      in patients with RBD who cannot take clonazepam due to either ineffectiveness or
      adverse effects. 

PMID- 24042526
TI  - Synchronized Babinski and Chaddock signs preceded the MRI findings in a case of
      repetitive transient ischemic attack.
AB  - We herein report a 53-year-old female with repeated transient ischemic attack
      (TIA) symptoms including 13 instances of right hemiparesis that decreased in
      duration over 4 days. Two separate examinations using diffusion weighted image
      (DWI) in magnetic resonance imaging (MRI) revealed normal findings, but we
      observed that both Babinski and Chaddock signs were completely synchronized with
      her right hemiparesis. We were only able to diagnose this case of early stage TIA
      using clinical signs. This diagnosis was confirmed 4 days after the onset by the
      presence of abnormalities on the MRI. DWI-MRI is generally useful when diagnosing
      TIA, but a neurological examination may be more sensitive, especially in the
      early stages. 

PMID- 24042527
TI  - Eosinophilic granulomatosis with polyangiitis of the major salivary glands: a
      case of sialadenitis in a young patient.
AB  - A 23-year-old man was referred to our Emergency Department due to an acute-onset
      hemoptysis and the associated bilateral swelling of all of his major salivary
      glands. The elevated levels of systemic inflammatory markers with
      hypereosinophilia and the concurrent presence of multiple lung infiltrates made
      it difficult to perform a differential diagnosis, as these symptoms can also be
      indicative of infectious, autoimmune or hematologic disorders. A histological
      examination of the patient's left submandibular gland revealed strong clues as to
      the final diagnosis of eosinophilic granulomatosis with polyangiitis with an
      atypical clinical presentation, thus allowing for the administration of early and
      successful conservative therapy. The outcome of our case suggests that systemic
      vasculitis represents a rare but possible cause of acute bilateral sialadenitis
      in young patients. 

PMID- 24042528
TI  - Development of allergic bronchopulmonary aspergillosis with central
      bronchiectasis over a 10-year period: the need to recheck allergen sensitization.
AB  - A 55-year-old woman visited our hospital for an investigation of central
      bronchiectasis, mucoid impaction and infiltrative shadows on chest CT. She had a
      10-year history of bronchial asthma; however, her adherence to treatment was
      poor. Based on the presence of peripheral blood eosinophilia and immediate
      cutaneous reactivity to Aspergillus fumigatus, the patient was clinically
      diagnosed with allergic bronchopulmonary aspergillosis. Her condition and CT
      findings improved with systemic corticosteroid therapy. It was found that the
      patient had not been sensitized to Aspergillus 10 years earlier, indicating that
      single testing is inadequate for the early diagnosis of this disease. 

PMID- 24042529
TI  - Successful treatment of recurrent candidemia due to candidal thrombophlebitis
      associated with a central venous catheter using a combination of fosfluconazole
      and micafungin.
AB  - We herein report the case of an 85-year-old woman presenting with right internal
      jugular vein candidal thrombophlebitis associated with central venous catheters
      (CTCVC). The infecting agent was Candida albicans, which caused recurrent
      candidemia five times in total. Micafungin (MCFG) alone was ineffective; however,
      the combination of MCFG with fosfluconazole (F-FLCZ) successfully treated the
      patient without a need for any anticoagulant or surgical therapies. To the extent
      of our knowledge, this is the first report of CTCVC being successfully treated
      with a combination of F-FLCZ and MCFG. These new antifungal agents have better
      efficacy, tolerability and bioavailability; therefore, they can be useful
      alternatives to classical combination therapies such as amphotericin-B and 5
      fluorocytosine. 

PMID- 24042530
TI  - Recurrent Gemella haemolysans meningitis in a patient with osteomyelitis of the
      clivus.
AB  - Systemic infection caused by G. haemolysans has rarely been reported. We herein
      describe the case of a 69-year-old woman with recurrent G. haemolysans meningitis
      that led to abducens nerve palsy. Osteomyelitis of the clivus was likely present
      at the first admission, which led to reinfection of the meninges because the
      course of antibiotic treatment was too short. The patient has remained free of
      relapse for one year after undergoing a second round of treatment that lasted 63
      days. In cases of G. haemolysans meningitis, coexisting infectious diseases, such
      as endocarditis and/or osteomyelitis, should therefore be investigated to prevent
      recurrence. 

PMID- 24042531
TI  - Invasive tracheobronchial aspergillosis in a patient with systemic lupus
      erythematosus-dermatomyositis overlap syndrome.
AB  - A 45-year-old man was referred to our hospital with a 3-month history of dyspnea,
      polyarthralgia, myalgia and weight loss. He was diagnosed with systemic lupus
      erythematosus/dermatomyositis overlap syndrome with lung involvement, which
      presented as organizing pneumonia. However, a bronchoscopic examination revealed
      the presence of multiple plaque-like white lesions with ulcers on the bronchial
      membrane, located mainly in the central airway. The pathological specimens
      obtained from bronchoscopy showed numerous filamentous fungal hyphae that were
      aggressively invading the bronchial walls, suggesting a diagnosis of invasive
      tracheobronchial aspergillosis. The present case, along with a review of the
      literature, demonstrates that invasive tracheobronchial aspergillosis can occur
      in patients who do not appear to be immunosuppressed. This case of aspergillosis
      should thus be recognized as an extremely rare presentation of an Aspergillus
      infection. 

PMID- 24042532
TI  - Multiple aortic thrombosis successfully treated using pharmacotherapy.

PMID- 24042533
TI  - Patent ductus arteriosus with pulmonary endarteritis.

PMID- 24042534
TI  - Mediastinal thyroid goiter with no accumulation on scintigraphy.

PMID- 24042535
TI  - Chronic abdominal pain in a hemodialysis patient.

PMID- 24042536
TI  - Meningitis with pneumocephalus originating from a sacral pressure ulcer.

PMID- 24042537
TI  - Biopsy of the temporal artery in a patient with giant cell arteritis.

PMID- 24042538
TI  - Characteristic radiologic features of systemic sclerosis.

PMID- 24042539
TI  - Production of gas phase NO2 and halogens from the photolysis of thin water films
      containing nitrate, chloride and bromide ions at room temperature.
AB  - Nitrate and halide ions coexist in particles generated in marine regions, around
      alkaline dry lakes, and in the Arctic snowpack. Although the photochemistry of
      nitrate ions in bulk aqueous solution is well known, there is recent evidence
      that it may be more efficient at liquid-gas interfaces, and that the presence of
      other ions in solution may enhance interfacial reactivity. This study examines
      the 311 nm photolysis of thin aqueous films of ternary halide-nitrate salt
      mixtures (NaCl-NaBr-NaNO3) deposited on the walls of a Teflon chamber at 298 K.
      The films were generated by nebulizing aqueous 0.25 M NaNO3 solutions which had
      NaCl and NaBr added to vary the mole fraction of halide ions. Molar ratios of
      chloride to bromide ions were chosen to be 0.25, 1.0, or 4.0. The subsequent
      generation of gas phase NO2 and reactive halogen gases (Br2, BrCl and Cl2) were
      monitored with time. The rate of gas phase NO2 formation was shown to be enhanced
      by the addition of the halide ions to thin films containing only aqueous NaNO3.
      At [Cl(-)]/[Br(-)] <= 1.0, the NO2 enhancement was similar to that observed for
      binary NaBr-NaNO3 mixtures, while with excess chloride NO2 enhancement was
      similar to that observed for binary NaCl-NaNO3 mixtures. Molecular dynamics
      simulations predict that the halide ions draw nitrate ions closer to the
      interface where a less complete solvent shell allows more efficient escape of NO2
      to the gas phase, and that bromide ions are more effective in bringing nitrate
      ions closer to the surface. The combination of theory and experiments suggests
      that under atmospheric conditions where nitrate ion photochemistry plays a role,
      the impact of other species such as halide ions should be taken into account in
      predicting the impacts of nitrate ion photochemistry. 

PMID- 24042541
TI  - Ebstein's anomaly and Down's syndrome.
AB  - We report on two cases presenting with a rare combination of Ebstein's anomaly
      and Down's syndrome. The first patient presented with respiratory distress, mild
      cyanosis and right heart failure immediately after delivery. The symptoms
      improved with heart failure medication. The patient remained asymptomatic on
      follow up. The second patient was diagnosed antenatally with marked apical
      displacement of the tricuspid valve and a very small functional right ventricle
      compared to the left ventricle. At birth, the patient presented with an extreme
      form of Ebstein's anomaly with severe cyanosis, marked right heart failure and
      ductal-dependent pulmonary blood flow. The patient died within days of birth. 

PMID- 24042540
TI  - Diagnostic accuracy of 18F-FDG PET/CT for assessing response to radiofrequency
      ablation treatment in lung metastases: a multicentre prospective study.
AB  - PURPOSE: To assess diagnostic accuracy of (18)F-FDG PET/CT at 3 months for the
      detection of local recurrence after radiofrequency ablation (RFA) of lung
      metastases. METHODS: The PET/CT scan at 3 months was compared with a baseline
      PET/CT scan from a maximum of 2 months before RFA, with the reference standard as
      recurrence diagnosed by CT during a 12-month follow-up. Local recurrence was
      diagnosed on the PET/CT scan if lesional uptake was greater than the mediastinal
      background. Maximum standardized uptake values (SUVmax) were recorded. ROC curve
      analysis for SUVmax was performed. Overall survival (OS) and time to local
      relapse were computed from the date of RFA using the Kaplan-Meier method
      (www.clinicaltrials.gov: NCT 00382252). RESULTS: Between 2005 and 2009, 89
      patients (mean age 65 years) underwent RFA for 115 lung metastases (mean size
      16.2 +/- 6.9 mm). The median SUVmax before RFA was 5.8 +/- 4. PET/CT at 3 months
      and the reference standard were available in 77 patients and 100 lesions.
      Accuracy was 66.00% (95% CI 55.85-75.18%), sensitivity 90.91% (95 % CI 58.72
      99.77 %), specificity 62.92% (95% CI 52.03-72.93%), PPV 23.26% (95% CI 11.76
      38.63%), and NPV 98.25% (95% CI 90.61-99.96%). One-year OS was 94.2% (95% CI 86.6
      97.5%) and the probability of being free of local recurrence 1 year after RFA was
      84.6% (95% CI 75.0-90.8%). CONCLUSION: The specificity of PET/CT at 3 months is
      low because of persistent inflammation, especially when the lesion is close to
      the pleura. This technique is useful for its negative predictive value, but
      positive findings need to be confirmed by histology before new treatment is
      planned.

PMID- 24042542
TI  - The salt discourse in 2013.

PMID- 24042543
TI  - Sodium reduction is a public health priority: reflections on the Institute of
      Medicine's report, sodium intake in populations: assessment of evidence.

PMID- 24042544
TI  - Getting the message right: reducing sodium intake saves lives.

PMID- 24042545
TI  - Flawed evidence should not derail sound policy: the case remains strong for
      population-wide sodium reduction.

PMID- 24042546
TI  - Extreme sodium reductions for the entire population: zealotry or evidence based?

PMID- 24042547
TI  - Physiology, not policy, drives sodium intake.

PMID- 24042548
TI  - Sodium: how and how not to set a nutrient intake recommendation.

PMID- 24042549
TI  - The IOM report fails to detect evidence to support dietary sodium guidelines.

PMID- 24042555
TI  - Pure-tone audiometry in otosclerosis: insufficient evidence for the diagnostic
      value of the Carhart notch.
AB  - OBJECTIVE: To evaluate whether the Carhart notch on pure-tone audiometry is
      reliable as a diagnostic test for predicting otosclerosis in patients with
      conductive hearing loss. Data Sources PubMed, Embase, the Cochrane Library,
      CINAHL, and Scopus. METHODS: A systematic search was conducted. Studies reporting
      original study data were included. After assessment of directness of evidence and
      risk of bias of the selected articles, the prevalences and the positive and
      negative predictive values were extracted. RESULTS: A total of 1402 unique
      studies was retrieved. Three of these satisfied the eligibility criteria. One
      study provided direct evidence, while all studies carried moderate to high risk
      of bias. One study with moderate directness of evidence and high risk of bias was
      not further analyzed. In a study with a high directness of evidence, a high risk
      of bias, and a low prevalence of otosclerosis (8%) in patients with conductive
      hearing loss, the presence of a Carhart notch at 2000 Hz increased the risk of
      otosclerosis with 33%. In a second study with moderate directness of evidence,
      moderate risk of bias, and a high prevalence of otosclerosis (72%) in patients
      with a surgically confirmed congenital ossicular anomaly or otosclerosis, the
      presence of a Carhart notch at 2000 Hz increased the risk of otosclerosis with
      2%. CONCLUSION AND RECOMMENDATION: Although there is insufficient high-quality
      evidence regarding the diagnostic value of the Carhart notch, it seems it is a
      useful hint for the presence of otosclerosis, but it cannot be used to confirm a
      diagnosis of otosclerosis.

PMID- 24042556
TI  - Risk factors for unplanned hospital readmission in otolaryngology patients.
AB  - OBJECTIVE: Identify the risk factors that predict 30-day unplanned readmission in
      hospitalized otolaryngology patients. STUDY DESIGN: Retrospective cohort study.
      SETTING: Single academic hospital. SUBJECTS AND METHODS: All otolaryngology
      admissions for the 1-year period between January 1, 2011, and December 31, 2011,
      at an academic hospital were reviewed. Univariate logistic regression and
      multivariate logistic regression, employing a backward elimination stepwise
      approach, were performed to identify risk factors for unplanned readmission to
      the hospital within 30 days of discharge from the otolaryngology service.
      RESULTS: There were 1058 patients that accounted for 1271 hospital admissions.
      The 30-day unplanned readmission rate for patients discharged from the
      otolaryngology service was 7.3% (93/1271). Significant predictors identified on
      univariate analysis were used to build a multivariable logistic regression model
      of risk factors for unplanned readmission. These risk factors included presence
      of a complication (odds ratio [OR] = 11.60, 95% confidence interval [CI], 7.11
      18.93), new total laryngectomy (OR = 4.72, 95% CI, 1.58-14.10), discharge
      destination of skilled nursing facility (OR = 2.70, 95% CI, 1.21-6.02), severe
      coronary artery disease or chronic lung disease (OR = 2.33, 95% CI, 1.38-3.93),
      and current illicit drug use (OR = 2.60, 95% CI, 1.27-5.34). The discriminative
      ability of the multivariate regression model to predict unplanned readmissions,
      as measured by the c-statistic, was 0.85. CONCLUSION: Otolaryngology patients
      have unique risk factors that predict unplanned readmission within 30 days of
      discharge. These data identify specific patient characteristics and care
      processes that can be targeted with quality improvement interventions to decrease
      unplanned readmissions.

PMID- 24042557
TI  - Response to "comparison of plaintiff and defendant expert witness qualification
      in malpractice litigation in otolaryngology".

PMID- 24042558
TI  - In response to "comparison of plaintiff and defendant expert witness
      qualification in malpractice litigation in otolaryngology".

PMID- 24042559
TI  - Re: "decision making in the choice of surgical management for preauricular
      sinuses with different severities".

PMID- 24042560
TI  - Response to "re: 'decision making in the choice of surgical management for
      preauricular sinuses with different severities'".

PMID- 24042561
TI  - Platelet gene therapy by lentiviral gene delivery to hematopoietic stem cells
      restores hemostasis and induces humoral immune tolerance in FIX(null) mice.
AB  - Here, we developed a clinically translatable platelet gene therapy approach for
      hemophilia B. Platelet-targeted FIX (2bF9) expression was introduced by
      transplantation of hematopoietic stem cells (HSCs) transduced with 2bF9
      lentivirus (LV). Sustained therapeutic levels of platelet-FIX expression were
      obtained in FIX(null) mice that received 2bF9 LV-transduced HSCs. Approximately 6
      39% of the platelets expressed FIX in the transduced recipients, which was
      sufficient to rescue the bleeding diathesis in FIX(null) mice in tail clipping
      models. Sequential bone marrow transplantation demonstrated that platelet-FIX
      expression in the secondary recipients was sustained, leading to phenotypic
      correction. Notably, none of the transduced recipients developed anti-FIX
      antibodies after platelet gene therapy. Only one of the nine recipients developed
      a low titer of inhibitory antibodies (1.6 BU/ml) after challenge with rhFIX.
      These data suggest that platelet gene therapy can not only restore hemostasis but
      also induce immune tolerance in hemophilia B mice, indicating that this approach
      may be a promising strategy for gene therapy of hemophilia B in humans.

PMID- 24042562
TI  - Prostate cancer: Increasing the potential of prostate biopsies with bioimpedance
      spectroscopy.

PMID- 24042565
TI  - Bladder cancer: urologists, time to take the helm as antimicrobial stewards.

PMID- 24042563
TI  - BCG immunotherapy for bladder cancer--the effects of substrain differences.
AB  - Genetic mutations have been progressively introduced to BCG by repeated serial
      passage over many decades of its culture and global dissemination. Thus, marked
      differences exist in the phenotype, antigenicity, reactogenicity, and clinical
      characteristics of the numerous substrains of BCG currently in use for bladder
      cancer immunotherapy. These differences influence proposed mycobacterial
      antitumour mechanisms and toxicity, potentially resulting in variations in
      clinical efficacy and adverse effects. However, although there is evidence of
      substrain-related differences in the clinical efficacy of BCG as a tuberculosis
      vaccine, evidence of an effect on bladder cancer immunotherapy remains elusive,
      owing to the lack of appropriately powered head-to-head comparative clinical
      trials, the nonstandardization of BCG manufacture, and variation in treatment
      protocols--possibly itself a response to underlying substrain differences.
      Advances in our understanding of mycobacterial genetics, structure and function,
      and host-pathogen interactions might explain differences in clinical practice and
      outcomes. These advances are guiding the identification of biomarkers for
      reactogenicity and efficacy, and the rational design of immunotherapeutic
      strategies to eliminate the use of live bacilli for bladder cancer therapy.

PMID- 24042568
TI  - Prostate cancer: Steroid enzyme mutated in CRPC.

PMID- 24042570
TI  - Genetic architecture controlling variation in grain carotenoid composition and
      concentrations in two maize populations.
AB  - KEY MESSAGE: Genetic control of maize grain carotenoid profiles is coordinated
      through several loci distributed throughout three secondary metabolic pathways,
      most of which exhibit additive, and more importantly, pleiotropic effects. The
      genetic basis for the variation in maize grain carotenoid concentrations was
      investigated in two F2:3 populations, DEexp * CI7 and A619 * SC55, derived from
      high total carotenoid and high beta-carotene inbred lines. A comparison of grain
      carotenoid concentrations from population DEexp * CI7 grown in different
      environments revealed significantly higher concentrations and greater trait
      variation in samples harvested from a subtropical environment relative to those
      from a temperate environment. Genotype by environment interactions was
      significant for most carotenoid traits. Using phenotypic data in additive,
      environment-specific genetic models, quantitative trait loci (QTL) were
      identified for absolute and derived carotenoid traits in each population,
      including those specific to the isomerization of beta-carotene. A multivariate
      approach for these correlated traits was taken, using carotenoid trait principal
      components (PCs) that jointly accounted for 97 % or more of trait variation.
      Component loadings for carotenoid PCs were interpreted in the context of known
      substrate-product relationships within the carotenoid pathway. Importantly, QTL
      for univariate and multivariate traits were found to cluster in close proximity
      to map locations of loci involved in methyl-erythritol, isoprenoid and carotenoid
      metabolism. Several of these genes, including lycopene epsilon cyclase,
      carotenoid cleavage dioxygenase1 and beta-carotene hydroxylase, were mapped in
      the segregating populations. These loci exhibited pleiotropic effects on alpha
      branch carotenoids, total carotenoid profile and beta-branch carotenoids,
      respectively. Our results confirm that several QTL are involved in the
      modification of carotenoid profiles, and suggest genetic targets that could be
      used for the improvement of total carotenoid and beta-carotene in future breeding
      populations.

PMID- 24042571
TI  - Fine mapping and chromosome walking towards the Ror1 locus in barley (Hordeum
      vulgare L.).
AB  - KEY MESSAGE: The Ror1 gene was fine-mapped to the pericentric region of barley
      chromosome 1HL. Recessively inherited loss-of-function alleles of the barley
      (Hordeum vulgare) Mildew resistance locus o (Mlo) gene confer durable broad
      spectrum disease resistance against the obligate biotrophic fungal powdery mildew
      pathogen Blumeria graminis f.sp. hordei. Previous genetic analyses revealed two
      barley genes, Ror1 and Ror2, that are Required for mlo-specified resistance and
      basal defence. While Ror2 was cloned and shown to encode a t-SNARE protein
      (syntaxin), the molecular nature or Ror1 remained elusive. Ror1 was previously
      mapped to the centromeric region of the long arm of barley chromosome 1H. Here,
      we narrowed the barley Ror1 interval to 0.18 cM and initiated a chromosome walk
      using barley yeast artificial chromosome (YAC) clones, next-generation DNA
      sequencing and fluorescence in situ hybridization. Two non-overlapping YAC
      contigs containing Ror1 flanking genes were identified. Despite a high degree of
      synteny observed between barley and the sequenced genomes of the grasses rice
      (Oryza sativa), Brachypodium distachyon and Sorghum bicolor across the wider
      chromosomal area, the genes in the YAC contigs showed extensive interspecific
      rearrangements in orientation and order. Consequently, the position of a Ror1
      homolog in these species could not be precisely predicted, nor was a barley gene
      co-segregating with Ror1 identified. These factors have prevented the molecular
      identification of the Ror1 gene for the time being.

PMID- 24042573
TI  - Dementia in China: current status.

PMID- 24042572
TI  - Characterization of OsMIK in a rice mutant with reduced phytate content reveals
      an insertion of a rearranged retrotransposon.
AB  - The rice low phytic acid (lpa) mutant Os-lpa-XS110-1(XS-lpa) has ~45 % reduction
      in seed phytic acid (PA) compared with the wild-type cultivar Xiushui 110.
      Previously, a single recessive gene mutation was shown to be responsible for the
      lpa phenotype and was mapped to a region of chromosome 3 near OsMIK
      (LOC_Os03g52760) and OsIPK1 (LOC_Os03g51610), two genes involved in PA
      biosynthesis. Here, we report the identification of a large insert in the intron
      of OsMIK in the XS-lpa mutant. Sequencing of fragments amplified through TAIL
      PCRs revealed that the insert was a derivative of the LINE retrotransposon gene
      LOC_Os03g56910. Further analyses revealed the following characteristics of the
      insert and its impacts: (1) the inserted sequence of LOC_Os03g56910 was split at
      its third exon and rejoined inversely, with its 5' and 3' flanking sequences
      inward and the split third exon segments outward; (2) the LOC_Os03g56910 remained
      in its original locus in XS-lpa, and the insertion probably resulted from
      homologous recombination repair of a DNA double strand break; (3) while the OsMIK
      transcripts of XS-lpa and Xiushui 110 were identical, substantial reductions of
      the transcript abundance (~87 %) and the protein level (~60 %) were observed in
      XS-lpa, probably due to increased methylation in its promoter region. The above
      findings are discussed in the context of plant mutagenesis, epigenetics and lpa
      breeding. 

PMID- 24042574
TI  - Vertebral artery dissection causing an acute C5 radiculopathy.

PMID- 24042575
TI  - Association between performance on neurology in-training and certification
      examinations.

PMID- 24042576
TI  - Migraine prevention with a supraorbital transcutaneous stimulator: a randomized
      controlled trial.

PMID- 24042577
TI  - Clinical reasoning: A 64-year-old woman with progressive quadriparesis.
      Transverse myelitis (TM).

PMID- 24042578
TI  - Teaching video neuroimages: complicated scapular winging.

PMID- 24042579
TI  - Teaching NeuroImages: Polymyalgia rheumatica and giant cell arteritis.

PMID- 24042581
TI  - Rapid diagnosis of aneuploidy in chromosomes 13, 18, 21, X and Y by quantitative
      fluorescence-PCR combined with short tandem repeat and fluorescence-labeled
      homologous gene quantitative-PCR using 4-color fluorescently labeled universal
      primers.
AB  - The present study aimed to develop a rapid diagnostic test of aneuploidy in
      chromosomes 13, 18, 21, X and Y through a program combining short tandem repeat
      (STR) typing with fluorescence-labeled homologous gene quantitative-polymerase
      chain reaction (fHGQ-PCR), which avoids misjudgment risks by using one method
      alone. Furthermore, fluorescently labeled universal primers not only ensure the
      accuracy of the results but also reduces the cost of fluorescent labels. The
      verification of DNA extracted from samples confirmed by karyotype analysis with
      quantitative fluorescence (QF)-PCR shows that the results obtained using the QF
      PCR program are consistent with the results of karyotype analysis in rapidly
      diagnosing the aneuploidy of chromosomes 13, 18, 21, X and Y.

PMID- 24042582
TI  - High performance low temperature carbon composite catalysts for flexible dye
      sensitized solar cells.
AB  - Roll-to-roll manufacturing of dye sensitized solar cells (DSSCs) requires
      efficient and low cost materials that adhere well on the flexible substrates
      used. In this regard, different low temperature carbon composite counter
      electrode (CE) catalyst ink formulations for flexible DSSCs were developed that
      can be simply and quickly coated on plastic substrates and dried below 150 
      degrees C. The CEs were investigated in terms of photovoltaic performance in
      DSSCs by current-voltage measurements, mechanical adhesion properties by bending
      and tape tests, electro-catalytic performance by electrochemical impedance
      spectroscopy and microstructure by electron microscopy. In the bending and tape
      tests, PEDOT-carbon composite catalyst layers exhibited higher elasticity and
      better adhesion on all the studied substrates (ITO-PET and ITO-PEN plastic, and
      FTO-glass), compared to a binder free carbon composite and a TiO2 binder enriched
      carbon composite, and showed lower charge transfer resistance (1.5-3 Omega cm(2))
      than the traditional thermally platinized CE (5 Omega cm(2)), demonstrating
      better catalytic performance for the tri-iodide reduction reaction. Also the TiO2
      binder enriched carbon composite showed good catalytic characteristics and
      relatively good adhesion on ITO-PET, but on ITO-PEN its adhesion was poor. A DSSC
      with the TiO2 binder enriched catalyst layer reached 85% of the solar energy
      conversion efficiency of the reference DSSC based on the traditional thermally
      platinized CE. Based on the aforementioned characteristics, these carbon
      composites are promising candidates for replacing the platinum catalyst in a high
      volume roll-to-roll manufacturing process of DSSCs. 

PMID- 24042580
TI  - SQSTM1 mutations in French patients with frontotemporal dementia or
      frontotemporal dementia with amyotrophic lateral sclerosis.
AB  - IMPORTANCE: Mutations in the SQSTM1 gene, coding for p62, are a cause of Paget
      disease of bone and amyotrophic lateral sclerosis (ALS). Recently, SQSTM1
      mutations were confirmed in ALS, and mutations were also identified in 3 patients
      with frontotemporal dementia (FTD), suggesting a role for SQSTM1 in FTD.
      OBJECTIVE: To evaluate the exact contribution of SQSTM1 to FTD and FTD with ALS
      (FTD-ALS) in an independent cohort of patients. DESIGN: A SQSTM1 mutation was
      first identified in a multiplex family with FTD by use of whole-exome sequencing.
      To evaluate the frequency of SQSTM1 mutations, we sequenced this gene in a cohort
      of patients with FTD or FTD-ALS, with no mutations in known FTD and ALS genes.
      SETTING: Primary care or referral center. PARTICIPANTS: An overall cohort of 188
      French patients, including 132 probands with FTD and 56 probands with FTD-ALS.
      MAIN OUTCOMES AND MEASURES: Frequency of SQSTM1 mutations in patients with FTD or
      FTD-ALS; description of associated phenotypes. RESULTS: We identified 4
      heterozygous missense mutations in 4 unrelated families with FTD; only 1 family
      had clinical symptoms of Paget disease of bone, and only 1 family had clinical
      symptoms of FTD-ALS, possibly owing to the low penetrance of some of the clinical
      manifestations. CONCLUSIONS AND RELEVANCE: Although the frequency of the
      mutations is low in our series (4 of 188 patients [2%]), our results, similar to
      those already reported, support a direct pathogenic role of p62 in different
      types of FTD.

PMID- 24042583
TI  - Indan-C60: from a crystalline molecule to photovoltaic application.
AB  - Crystalline Indan-C60 and its photovoltaic application were studied. Microsheets
      and aloe-like micro-nano superstructures can be assembled from Indan-C60. Indan
      PC61BM derived from Indan-C60 was further investigated as an acceptor for OPV
      devices, which shows a higher Voc, FF, and PCE than those obtained using PC61BM. 

PMID- 24042584
TI  - Biomechanics of human tongue movement during bolus compression and swallowing.
AB  - We evaluated the effects of gel consistency and bolus volume on ingestion in
      humans. Eight healthy men were asked to ingest liquids, and sample foods of
      different gel consistencies and volumes, as usual. Tongue pressure against the
      hard palate was recorded at five points, and bolus flow was recorded using
      videoendoscopic images. The number of squeezes increased as gel consistency and
      volume increased. The integrated magnitude of tongue pressure during squeezing
      increased with increasing gel consistency. Bolus propulsion into the pharynx was
      affected by bolus characteristics, and location of the bolus head at the onset of
      pharyngeal swallowing was not related to squeezing behavior. The trigger point at
      which pharyngeal swallowing began was subject-dependent. During swallowing, the
      magnitude of tongue pressure moderately increased with increasing gel
      consistency, as compared with squeezing. Tongue pressure was not related to bolus
      volume. The current results suggest that patterns of tongue pressure during
      squeezing and swallowing are differentially affected by bolus conditions.
      However, healthy subjects differed in the techniques used for squeezing and
      swallowing.

PMID- 24042585
TI  - Retrospective analysis of 36 ameloblastoma cases in Laos.
AB  - We conducted a retrospective study of 36 cases of ameloblastoma from the files of
      Mittaphap Hospital in Vientiane Capital, Laos. Clinical findings showed an
      average patient age of 31.0 +/- 3.8 years, with a slight male preponderance.
      Radiographically, all of the lesions showed multicystic radiotranslucency. Twenty
      four patients underwent tumor resection and 12 underwent tumor enucleation. Of
      those patients, four underwent additional surgery because of tumor recurrence.
      This is the first report in the English literature of ameloblastoma cases from
      Laos.

PMID- 24042586
TI  - Dental development in children with severe molar-incisor hypomineralization in
      Samsun, Turkey.
AB  - Anomalies in amelogenesis may be due to developmental defects or abnormalities in
      different components of developing teeth and can affect dental development. We
      compared dental development in a group of children with molar-incisor
      hypomineralization (MIH) with that in age- and sex-matched controls. Dental age
      was determined using panoramic radiographs of 105 children (59 girls, 46 boys)
      aged 7-11 years with severe MIH, and the findings were compared with those from
      105 healthy age- and sex-matched controls. Although accelerated dental
      development was noted in the MIH group, the difference between the MIH and
      control groups was not statistically significant (P < 0.05). Furthermore, no
      relationship was found between number of affected teeth and the difference
      between dental and chronological age. In conclusion, children with severe MIH had
      slightly accelerated dental development as compared with controls.

PMID- 24042587
TI  - Osteogenic transcription factors and proto-oncogene regulate bone sialoprotein
      gene transcription.
AB  - Runt homeodomain protein 2 (Runx2), distalless 5 (Dlx5) and Smad1 are
      transcription factors that play critical roles in controlling the differentiation
      of osteoblasts and mineralization of bone. Proto-oncogene tyrosine-protein
      kinase, Src, is an enzyme encoded by the Src gene. The normal cellular gene is
      called cellular-Src (c-Src). Bone sialoprotein (BSP), a protein implicated in the
      initial mineralization of newly formed bone, is an early phenotypic marker of
      differentiated osteoblasts. In this study, we used overexpression plasmids with
      Runx2, Dlx5, Smad1 or c-Src inserts to search for the effects of these
      transcription factors and proto-oncogene on BSP gene expression using rat
      osteoblast-like ROS 17/2.8. When we used Runx2, Dlx5 or c-Src overexpression
      plasmids for the transfection, BSP and Runx2 mRNA levels were increased in ROS
      17/2.8 cells. However, overexpression of Smad1 did not induce BSP and Runx2 mRNA.
      Transient transfection analyses were performed using chimeric constructs of the
      rat BSP gene promoter linked to a luciferase reporter gene. Transfection of ROS
      17/2.8 cells with Runx2, Dlx5 or c-Src overexpression plasmid increased the
      luciferase activities of the constructs, pLUC3 (-116 to +60), pLUC4 (-425 to +60)
      and pLUC5 (-801 to +60). However, Smad1 overexpression had no effect on the
      luciferase activities. These results demonstrate that overexpression of Runx2,
      Dlx5 or c-Src stimulates BSP transcription, and suggest that Runx2, Dlx5 and c
      Src might be crucial transcriptional regulators of mineralization and bone
      formation.

PMID- 24042588
TI  - Electromyography of masticatory muscles after denture relining with soft and hard
      denture liners.
AB  - We evaluated electromyograms of masticatory muscles after denture relining with
      soft and hard liners. In total, 44 patients with complete dentures were studied:
      22 underwent chairside relining of mandibular dentures with a soft, silicone
      based liner (Mucopren Soft); the other 22 underwent relining with a hard, acrylic
      resin-based liner (Kooliner). Electromyograms of the masseter and temporal
      muscles were obtained before (T0) and 90 days after (T90) relining. Participants
      performed a maximum voluntary contraction (static test), on which percentage
      overlapping coefficient (%), mandibular displacement (%), and standardized
      electromyographic activity, i.e., impact, (uV / uVs %) were analyzed.
      Participants were also asked to chew a wafer, cereal bar, and peanuts (dynamic
      test) to determine symmetrical mastication index (SMI%), frequency (Hz), and
      impact. The data were analyzed using a generalized linear model (alpha= 0.05). On
      the static test, mandibular displacement was lower and impact was higher at T90,
      as compared with baseline. On the dynamic test, SMI and impact were higher after
      relining for all foods. Frequency at T90 was higher only during cereal and peanut
      mastication. There were no differences between groups except for greatest impact
      during wafer chewing in patients with hard liners. Relining with hard and soft
      materials increased electromyographic activity and improved masticatory function.
      There was little difference between groups.

PMID- 24042589
TI  - Evaluation of bioactive glass and platelet-rich plasma for bone healing in rabbit
      calvarial defects.
AB  - Bone regeneration is an important objective in clinical dental practice and has
      been used for different applications. The aim of this study was to evaluate the
      effectiveness of platelet-rich plasma (PRP) and bioactive glass (BG) for bone
      healing of surgical calvarial defects in rabbits. Two 8-mm defects were prepared
      in the parietal bones of ten animals, and the animals were randomly assigned to
      two groups. In each group, two subgroups were created with five defects each: BC 
      blood clot, BG, PRP and PRP + BG. Thus, four treatments were performed with five
      specimens each. The animals were sacrificed after 12 weeks and the specimens were
      analyzed radiographically, histologically and histomorphometrically. Data were
      subjected to ANOVA and Tukey's tests (alpha = 0.05). Outcomes demonstrated that
      the PRP group had higher bone density (%) values than the groups not treated with
      PRP (P < 0.05). Histometrically, both groups treated with PRP (PRP: 25.6 +/- 9.9;
      PRP+BG: 25.8 +/- 12.4) demonstrated higher percentages of new bone formation than
      the groups not treated with PRP (BG: 6.1 +/- 4.3; BC: 7.8 +/- 5.6) (P < 0.05).
      The results suggested that PRP improved bone repair and that bioactive glass
      alone, or in association with PRP, did not improve bone healing.

PMID- 24042590
TI  - Fluoride content in plaque solids and fluid after ingestion of fluoridated milk.
AB  - This study explored differences in dental biofilm solids and fluid fluoride after
      ingestion of NaF or Na2FPO3 in milk or non-fluoridated milk. Eighteen volunteers
      ingested 1 mg fluoride in 200 mL of milk or 200 mL of non-fluoridated milk.
      Biofilm samples were collected at baseline, 30, 60, and 240 min and biofilm
      solids and fluid were micro-analyzed for fluoride. Analysis of variance was
      performed and the total delivery, retention, and clearance of fluoride to biofilm
      solids and fluid were estimated as the area under the curve between 0 and 240
      min. No statistically significant differences were found for baseline values.
      Biofilm fluid fluoride values ranged from 0.11 +/- 0.05 to 0.21 +/- 0.08 ug F/mL
      while biofilm solid values ranged from 0.62 +/- 0.39 to 1.75 +/- 1.16 ug F/g.
      Biofilm fluid values were significantly lower at 60 min for Na2FPO3 in milk.
      Clearance profiles for biofilm fluid diverged after the initial 60 min. Na2FPO3
      had a smaller area under the curve from 60 to 240 min than NaF. Results of this
      study indicate that the release and clearance of fluoride in biofilm vary among
      fluoridation compounds and that the concentrations in biofilm solids and fluid
      also vary and are not correlated to each other in many cases.

PMID- 24042591
TI  - Stress distribution in fixed-partial prosthesis and peri-implant bone tissue with
      different framework materials and vertical misfit levels: a three-dimensional
      finite element analysis.
AB  - The purpose of this study was to evaluate the influence of superstructure
      material and vertical misfits on the stresses created in an implant-supported
      partial prosthesis. A three-dimensional (3-D) finite element model was prepared
      based on common clinical data. The posterior part of a severely resorbed jaw with
      two osseointegrated implants at the second premolar and second molar regions was
      modeled using specific modeling software (SolidWorks 2010). Finite element models
      were created by importing the solid model into mechanical simulation software
      (ANSYS Workbench 11). The models were divided into groups according to the
      prosthesis framework material (type IV gold alloy, silver-palladium alloy,
      commercially pure titanium, cobalt-chromium alloy, or zirconia) and vertical
      misfit level (10 um, 50 um, and 100 um) created at one implant-prosthesis
      interface. The gap of the vertical misfit was set to be closed and the stress
      values were measured in the framework, porcelain veneer, retention screw, and
      bone tissue. Stiffer materials led to higher stress concentration in the
      framework and increased stress values in the retention screw, while in the same
      circumstances, the porcelain veneer showed lower stress values, and there was no
      significant difference in stress in the peri-implant bone tissue. A considerable
      increase in stress concentration was observed in all the structures evaluated
      within the misfit amplification. The framework material influenced the stress
      concentration in the prosthetic structures and retention screw, but not that in
      bone tissue. All the structures were significantly influenced by the increase in
      the misfit levels.

PMID- 24042592
TI  - Associations of duration of smoking cessation and cumulative smoking exposure
      with periodontitis.
AB  - This cross-sectional study investigated associations of cumulative smoking
      exposure and duration of smoking cessation with periodontitis and evaluated the
      effects of biological, behavioral, and social risk variables on these
      associations. The sample comprised 705 adults of both sexes (age, 35-65 years)
      who underwent a full-mouth periodontal examination. Subjects were classified
      according to smoking status as nonsmokers, former smokers, and current smokers,
      and univariate and multivariate analysis was used to evaluate associations
      between periodontitis prevalence and potential risk variables. The rates of
      periodontitis among nonsmokers, former smokers, and current smokers were 25.6%,
      29.3%, and 45.1% respectively. After adjusting for other periodontal risk
      variables the odds ratio (95% confidence interval) for periodontitis was 3.09
      (1.98-4.92) for former smokers and 5.24 (2.61-8.97) for current smokers. A
      significant dose-response relationship between pack-years of smoking and
      periodontitis prevalence was observed, as was a significant decrease in the risk
      of periodontitis as years of smoking cessation increased. Cumulative smoking
      exposure and duration of smoking cessation were significantly associated with
      periodontitis.

PMID- 24042593
TI  - Pemphigus, discoid lupus erythematosus, and dermatomyositis during an 8-year
      follow-up period: a case report.
AB  - A 36-year-old Thai woman presented with a painful, burning sensation in the
      gingiva and desquamative gingivitis. Findings from histopathologic and direct
      immunofluorescence examination of the maxillary gingiva confirmed a diagnosis of
      pemphigus. Two months later, she developed a round erythematous lesion on her
      face, and findings from a skin biopsy were consistent with lupus erythematosus.
      Four years after initial presentation, the patient developed amyotrophic
      dermatomyositis. Seven years after initial presentation, she developed joint pain
      and tenositis of the neck, shoulders, knees and ankles, which was diagnosed as
      asymmetric polyarthritis and multiple enthesopathy. There are no previous reports
      of pemphigus, discoid lupus erythematosus, and dermatomyositis in a Thai
      patient.Fluocinolone acetonide 0.1% in Orabase and systemic steroid were
      effective in treating oral PV in this patient. The gingiva showed complete
      remission after 10 months of treatment and remission with recession at 8.5 years
      of follow-up.

PMID- 24042594
TI  - Segmental odontomaxillary dysplasia: report of a case emphasizing
      histopathological, immunohistochemical and scanning electron microscopic
      features.
AB  - Segmental odontomaxillary dysplasia (SOD) is a rare developmental disorder of the
      maxilla, and there is little information on its morphological features. Thus, the
      present article describes a case of SOD focusing on its histopathological,
      immunohistochemical and scanning electron microscopic features. Several dental
      abnormalities were present, including numerous dentin and pulp defects, altered
      composition of hard tissue, and proliferation of myofibroblasts in the pulp and
      the soft tissue surrounding affected teeth. This myofibroblastic proliferation
      was identified for the first time in SOD and may be involved in both bone and
      tooth resorption mechanisms.

PMID- 24042595
TI  - Fifteen-year clinical performance of a resin-bonded fixed partial denture seated
      with a thione primer and a tri-n-butylborane-initiated luting agent.
AB  - This article reports the clinical performance of a resin-bonded fixed partial
      denture (FPD) made of type IV gold alloy. The retainers were air-abraded with
      alumina particles and primed with a single-liquid thione priming agent
      (Metaltite). The FPD was then seated with a tri-n-butylborane-initiated adhesive
      resin (Super-Bond). After 15 years, the FPD is still functioning satisfactorily.
      The present materials and techniques are applicable to minimally invasive fixed
      prosthodontic treatments.

PMID- 24042596
TI  - Left ventricular rupture after double valve replacement in a patient with
      myocarditis due to myasthenia gravis.
AB  - Myasthenia gravis is an autoimmune disease characterised by weakness of the
      skeletal muscles, with remissions and exacerbations due to antibodies acting on
      the acetylcholine receptors. This leads to the characteristic defect transmission
      in the neuromuscular junction. Treatment includes anticholinesterase agents,
      thymectomy, and immunosuppression. Surgical thymectomy can induce remission or
      improvement, allowing for reduction in the immunosuppressive treatment. The case
      of an 84-year-old female patient with myasthenia gravis, aortic valve stenosis,
      mitral valve regurgitation and myocarditis is described. The development of
      myocarditis was related to inflammatory cell infiltration, and progressive and
      additive focal cellular necrosis associated with reactive myocardial fibrosis.
      After replacement of the mitral valve, complications arose when a rupture of the
      left ventricular posterior wall occurred, which caused massive bleeding and
      sudden death on the operating table. 

PMID- 24042597
TI  - The Impact of Intramuscular-Inserted Hooked Wire Electrodes and Specific
      Stimulation Parameters.

PMID- 24042598
TI  - Ant Colony Optimization Tuning PID Algorithm for Precision Control of Functional
      Electrical Stimulation.

PMID- 24042599
TI  - Dynamic Echomyography Shows That FES in Peripheral Denervation does not Hamper
      Muscle Reinnervation.

PMID- 24042600
TI  - Pattern Generating Networks in the Human Lumbar Spinal Cord: Electrophysiology
      and Computer Modeling.

PMID- 24042601
TI  - Prevention of Orthostatic Hypotension with Electric Stimulation in Persons with
      Acute Spinal Cord Injury.

PMID- 24042602
TI  - Using acceleration sensors to quantify symptoms during deep brain stimulation
      surgery.

PMID- 24042603
TI  - A Case Study for a New Approach of a Constant Pressure Perfused Ex-Vivo Model of
      the Equine Larynx.

PMID- 24042604
TI  - First Results with a Prototype of a new Cochlear Implant Electrode featuring
      Shape Memory Effect.

PMID- 24042605
TI  - Cortico-Muscular Coherence Analysis Under Voluntary, Stimulated and Imaginary
      Neuromuscular Activities.

PMID- 24042606
TI  - Neural Activation for Different Electrode Designs in Subretinal Implants: a
      Modeling Study.

PMID- 24042607
TI  - Effects of transcutaneous spinal cord stimulation on voluntary locomotor activity
      in an incomplete spinal cord injured individual.

PMID- 24042608
TI  - Evaluation of Spinal Cord Response During Magnetic Stimulation of the Lumbar
      Area.

PMID- 24042609
TI  - Modelling a BCI system to estimate FES stimulation intensity for individual
      stroke survivors in foot drop cases.

PMID- 24042610
TI  - Towards the Development of Implantable Connectors with High Contact Number.

PMID- 24042611
TI  - Comparison of Current and Voltage Control Techniques for Neuromuscular Electrical
      Stimulation in the Anterior Thigh.

PMID- 24042612
TI  - Recovery of Tetanic Contractility of Denervated Muscle: A Step Toward a Walking
      Aid for Foot Drop.

PMID- 24042613
TI  - Expected Effects of Auricular Vagus Nerve Stimulation in Dystonia.

PMID- 24042614
TI  - The Effect of Spinal Cord Stimulation on Epileptic Seizures Suppression.

PMID- 24042615
TI  - High-Intensity Virtual-reality Arm plus FES-leg Interval Training in Individuals
      with Spinal Cord Injury.

PMID- 24042616
TI  - Compliance monitoring of home based electrical stimulation training of elderly
      subjects.

PMID- 24042617
TI  - Step Side Recognition Based on Handle Reaction Forces During Functional
      Electrical Stimulation.

PMID- 24042618
TI  - Stimulus Artifact Removal of Semg Signals Detected During Functional Electrical
      Stimulation.

PMID- 24042619
TI  - Investigating the Influence of 3D Cell Morphology on Neural Response During
      Electrical Stimulation.

PMID- 24042620
TI  - Mechanisms of rhythm generation of the human lumbar spinal cord in response to
      tonic stimulation without and with step-related sensory feedback.

PMID- 24042621
TI  - Intraoperative optical flow based tremor evaluation - a feasibility study.

PMID- 24042622
TI  - Functional Electrical Stimulation in Spinal Cord Injury: Clinical Evidence versus
      Daily Practice.

PMID- 24042623
TI  - Bioimpedance- and EMG-Triggered FES for Improved Protection of the Airway During
      Swallowing.

PMID- 24042624
TI  - Laser-structured ceramic adapters for reliable assembly of flexible thin-film
      electrodes.

PMID- 24042625
TI  - Comparison of electric field distribution between simulation and measurement
      results in vitro.

PMID- 24042626
TI  - WITHDRAWN:Towards physiological ankle movements with the ActiGait implantable
      drop foot stimulator in chronic stroke.
AB  - Ahead of Print article withdrawn by publisher.

PMID- 24042627
TI  - Establishment of an in Vitro Model for Stress Testing of Vagal Nerve Cuff
      Electrodes.

PMID- 24042628
TI  - Selectivity of transcutaneous stimulation of lumbar posterior roots at different
      spinal levels in humans.

PMID- 24042629
TI  - Cardiorespiratory and Metabolic Responses During FES Leg Exercise: Health and
      Fitness Benefits Update.

PMID- 24042630
TI  - The Influence of Flux on the Reliability of Solder-Sealed Hermetic Packages for
      Active Implantable Medical Devices.

PMID- 24042631
TI  - A Wireless Functional Electrical Stimulation System.

PMID- 24042632
TI  - Phantom Studies of Neutron Capture of Boron Containing Magnetic Nanoparticles.

PMID- 24042633
TI  - Counter Pulsation by Triggered Electrical Stimulation of Leg Muscles for Chronic
      Heart Failure Treatment.

PMID- 24042634
TI  - PaQ(r), a simple 3-day basal/bolus insulin delivery device, in people with type 2
      diabetes.

PMID- 24042635
TI  - Lab-on-a-chip device for fabrication of therapeutic microbubbles on demand.

PMID- 24042636
TI  - Simulation of Magnetic Nanoparticles in Blood Flow for Magnetic Drug Targeting
      Applications.

PMID- 24042637
TI  - Optimization of a Miniaturized Electrospray Device by Combining High Speed Video
      Imaging and Fem Modelling.

PMID- 24042638
TI  - In-Vitro Evaluation of a Drainage Catheter with Integrated Bioimpedance
      Electrodes to Determine Ventricular Size.

PMID- 24042639
TI  - Adaptive Radiotherapy Using Deformable Image Registration - A Concept for
      Individualised Radiation Treatments.

PMID- 24042640
TI  - Characterization of Respiratory Patterns During Assisted Mechanical Ventilation
      in Experimental ARDS.

PMID- 24042641
TI  - Design of Miniaturized Electro Spray Instrument for Gene and Drug Therapeutic
      Treatment of IPF.

PMID- 24042642
TI  - Characterisation of Cell Growth on Titanium Scaffolds Made by Selective Laser
      Melting for Tissue Engineering.

PMID- 24042643
TI  - Production of Multimodal Embolisation Particles - Challenges and Possibilities.

PMID- 24042644
TI  - Parameters of Endothelial Function are Dependent on Polymeric Surface Material.

PMID- 24042645
TI  - Development of a Test Facility for Microfluidic Characterization of Glaucoma
      Drainage Devices.

PMID- 24042646
TI  - Quasi-Continuous Particle Size Characterisation During Accelerated Stent Radial
      Fatigue Test.

PMID- 24042647
TI  - Large Scale Preparation and Analysis of Hyperhydrophilic Dental Implants with
      MUSLA Titanium Surface.

PMID- 24042648
TI  - Evaluating a Novel Class of Biomaterials: Magnesium-Containing Layered Double
      Hydroxides.

PMID- 24042649
TI  - Impact of Sterilization Procedures on the Stability of Parylene Based Flexible
      Multilayer Structures.

PMID- 24042650
TI  - Nanoporous Silica Films as Novel Biomaterial: Applications in the Middle Ear.

PMID- 24042652
TI  - Investigation of Different Tissue Samples with MUCT and MPS for Determination of
      Iron Oxide Concentration in Tracers for MPI.

PMID- 24042651
TI  - Fluid Dynamic Load of Polymers Used as Encapsulation Material for Implantable
      Microsystems.

PMID- 24042653
TI  - Release of 125I-RhBMP-2 from Foamed Poly-(D,L)-Lactide.

PMID- 24042654
TI  - Preparation and Analysis of PCL Spun Chitosan Scaffolds as Guidance Channels for
      Peripheral Nerve Regeneration.

PMID- 24042655
TI  - Development Of A Tunable Drug Delivery System From Biodegradable Scaffolds Via
      Layer By Layer Deposition.

PMID- 24042656
TI  - Influence of Heat Treatment on the Degradation Behaviour of Degradable Magnesium
      Based Implants.

PMID- 24042657
TI  - Adjustment of the Mechanical Properties of Silicone for Applications in the
      Middle Ear.

PMID- 24042658
TI  - Evaluation and comparison of in vitro and in vivo degradation kinetics of
      magnesium.

PMID- 24042659
TI  - Resorbable Interference Screws Made of Magnesium Based Alloy.

PMID- 24042660
TI  - Biofunctionalization of Polymer Implant Surfaces: From Drug Delivery to Stable
      Surface Functionality.

PMID- 24042661
TI  - 3D printed chitosan / hydroxyapatite scaffolds for potential use in regenerative
      medicine.

PMID- 24042662
TI  - Steering of an electrospinning jet by dynamic manipulation of the electric field.

PMID- 24042663
TI  - Construction of a Spectrometer to Measure the Cotton-Mouton Effect of
      Superparamagnetic Iron Oxide Nanoparticles.

PMID- 24042664
TI  - Design of Antibacterial Copolymers for Implant Coatings.

PMID- 24042665
TI  - Applicability of Degradable Magnesium LAE442 Alloy Plate-Screw-Systems in a
      Rabbit Model.

PMID- 24042666
TI  - Plasma Nanofilms as Biocompatible and Antibacterial Coatings for Biosensors.

PMID- 24042667
TI  - Investigation of in Vitro Drug Release Behaviour of Drug-Eluting Stents Using a
      Perfusion Culture System.

PMID- 24042668
TI  - Patient-Individual Hip Cups: Simulation-Based Design and Sheet Metal Forming
      Manufacturing.

PMID- 24042669
TI  - New Developments in Device-Associated Bloodstream Infections.

PMID- 24042671
TI  - Biocompatibility evaluation of MEMS packaging materials for implantable devices.

PMID- 24042670
TI  - Machining of Biocompatible Ceramics with Femtosecond Laser Pulses.

PMID- 24042672
TI  - The Biodegradable Magnesium Stent as an Alternative Treatment in Cases of Chronic
      Ventilation Disorders of the Paranasal Sinuses.

PMID- 24042673
TI  - Entwicklung von schichtweise ausgerichteten Faserverbundstrukturen.

PMID- 24042674
TI  - Effects of laser parameters and scanning strategy on structural and mechanical
      properties of 3D NiTi implants fabricated with selective laser melting.

PMID- 24042675
TI  - Magnesium as a biomaterial and its biological interactions.

PMID- 24042676
TI  - Establishment of an in vitro evaluation system for drug-coated ballons.

PMID- 24042677
TI  - Finite element simulation of myocardial stabilising structures and development of
      new designs.

PMID- 24042678
TI  - Stiffness Properties of a Shape-Changing Implant for Fracture Fixation: A
      Preliminary Study.

PMID- 24042679
TI  - Development of an Injectable Polymer-Based Local Drug Delivery System for
      Subconjunctival Treatment of Glaucoma.

PMID- 24042681
TI  - Characterization of New Biodegradable Magnesiumalloys.

PMID- 24042680
TI  - Influence of HDI Fixation on the Mechanical Properties of Porcine Pericardial
      Tissue for Heart Valve Engineering.

PMID- 24042682
TI  - Finite Element Study of Degradable Intramedullary Nails out of Magnesium Alloy
      for Ovine Tibiae.

PMID- 24042683
TI  - Different cell populations are inducible by BMP-2 covalently covered Bioverit(r)
      II implants in rabbit subcutis and middle ear.

PMID- 24042684
TI  - Spider Silk - a Versatile Biomaterial for Tissue Engineering and Medical
      Applications.

PMID- 24042685
TI  - Infiltration of 3D printed tricalciumphosphate scaffolds with biodegradable
      polymers and biomolecules for local drug delivery.

PMID- 24042686
TI  - Specific Surface Modification Of Cochlear Implant Electrode Carriers For
      Enhancement Of Spiral Ganglion Cell Growth.

PMID- 24042687
TI  - Machining of Biocompatible Polymers with Shaped Femtosecond Laser Pulses.

PMID- 24042688
TI  - Proof of Concept of a New Glucose Sensing Technology: Color-Changing Hydrogels
      Including au Nanoparticles.

PMID- 24042689
TI  - The Influence of Machining on Residual Stresses and Corrosion Behavior of MgLa2
      Osteosynthesis Plates.

PMID- 24042690
TI  - Continuative Studies for Inserting Stimulus-Responsive Functions in Hydrogels for
      Local Drug Delivery.

PMID- 24042691
TI  - Antibacterial Silica Nanoparticles with PH-Sensitive Release Proprieties as
      Fillers for Dental Composite Materials.

PMID- 24042692
TI  - Comparison between simulation results and DEXA investigation of the bone
      remodelling after implanting a cementless long stem hip prosthesis.

PMID- 24042693
TI  - Enhanced Endothelialization of PCL Through Chemical Activation, Protein
      Precoating and VEGF Stimulation.

PMID- 24042694
TI  - Dynamische In-Vitro-Studie zur Stromungsabhangigkeit der Degradationsrate von
      Magnesium.

PMID- 24042695
TI  - Surface Patterning Of Cochlear Implant Electrode Arrays.

PMID- 24042696
TI  - Monitoring Polyelectrolyte Multilayer Assembly and Stability on Non-Transparent
      Rough Metal Surfaces.

PMID- 24042697
TI  - Prosthetic radial head stem pull-out as a mode of failure: a biomechanical study.
AB  - PURPOSE: Press-fit cementless radial head implant longevity relies on adequate
      bone ingrowth. Failed implant osseointegration remains a clinical concern and has
      been shown to lead to prosthetic failure. The purpose of this study was to test
      the hypothesis that implants with sufficient initial press-fit stability would be
      less likely to fail due to implant pull-out, as demonstrated by an increasing
      amount of energy required to remove the prosthesis from the canal. METHODS: Ten
      cadaveric radii were implanted with five sizes (6-10 mm in 1-mm increments) of
      grit-blasted, cementless radial head stems. A customised slap hammer was used to
      measure the energy required to remove each stem. Stem-bone micromotion was also
      measured. RESULTS: The suboptimally sized stem (Max - 1) (i.e. 1 mm undersized)
      required less energy (0.5 +/- 0 J) to pull out than the optimally sized stem
      (Max) (1.7 +/- 0.3 J) (p = 0.008). The optimally sized stem demonstrated greater
      initial stability (45 +/- 7 MUm) than the suboptimally sized stem (79 +/- 12 MUm)
      (p = 0.004). CONCLUSIONS: This investigation demonstrates the importance of
      obtaining adequate press-fit stability for the prevention of radial head stem
      pull-out failure. These data add to the relatively scant knowledge in the
      literature regarding radial head biomechanics. The energy required to remove a
      prosthetic radial head ingrowth stem decreases in conjunction with diameter. The
      use of an inadequately sized stem increases the stem's micromotion as well as the
      risk of prosthetic loosening due to pull-out.

PMID- 24042698
TI  - Are there sex differences in acute coronary syndrome presentation?: a guide
      through the maze.

PMID- 24042700
TI  - A new method for the quantification of aortic calcification by three-dimensional
      micro-computed tomography.
AB  - To gain a better understanding of the mechanisms that underpin aortic
      calcification, rodent models have been previously utilised. Regions of calcium
      and phosphate deposition are commonly visualised using labor-intensive two
      dimensional histomorphometric techniques. In this study, we developed a novel
      micro-computed tomography (uCT) imaging protocol to quantify calcification in
      vascular tissues using high resolution three-dimensional (3D) reconstructions of
      aortae derived from the well-established Ecto-nucleotide
      pyrophosphatase/phosphodiesterase-1 knockout (Enpp1-/-) mouse model of medial
      aortic calcification. A dual-contrast method was employed for specimen
      preparation and the application of corn oil as a submersion medium for the
      samples during scanning, which allowed the definition and quantification of soft
      tissue. 3D uCT was utilised to produce reconstructions of calcified and non
      calcified aortae. A highly accurate quantification of a standardized region of
      calcium deposition was undertaken on these reconstructions. An excellent
      correlation between images obtained from uCT and those obtained with Alizarin red
      staining, of whole aortae for calcium deposition, was observed. This imaging
      protocol provides a powerful tool for studying the development of aortic
      calcification and potential therapeutic approaches for clinical intervention. 

PMID- 24042699
TI  - Craving, cue reactivity, and stimulus control among early-stage young smokers:
      effects of smoking intensity and gender.
AB  - INTRODUCTION: Smoking initiation usually begins in adolescence, but how and for
      whom nicotine dependence emerges during this period is unclear. The cue
      reactivity paradigm is well suited to examine one marker of dependence: craving
      related stimulus control, i.e., the ability of environmental cues to elicit
      craving to smoke. This study examined the effects of both level of smoking
      involvement (daily vs. occasional smoking) and gender on reactivity to both
      smoking and alcohol cues. METHODS: Young (age range 16-20; 42% female) daily (n =
      55) and occasional (n = 52) smokers were exposed to each of three counterbalanced
      cues: (a) in vivo smoking (e.g., sight, smell, lighting of cigarette), (b)
      alcohol (e.g., opening, pouring, and smell of preferred beverage), and (c)
      neutral cue. RESULTS: Daily smokers exhibited higher levels of tonic (i.e.,
      noncue-elicited) craving than did occasional smokers. Both groups showed
      significant increases in craving in response to cues (i.e., cue-elicited
      craving), with little evidence that cue-elicited craving differed between groups.
      Females were more cue reactive to both the alcohol and smoking cues than males,
      particularly for the positively reinforced aspects of smoking (i.e., hedonic
      craving). There were no gender * group interaction effects in response to either
      the alcohol or the smoking cue. CONCLUSIONS: Findings show the presence of cue
      elicited craving even among occasional smokers and are consistent with literature
      demonstrating heightened sensitivity to environmental cues among females. Cue
      elicited craving may be one mechanism that contributes to the maintenance of
      smoking behavior and perhaps to the development of nicotine dependence within
      early stage smokers.

PMID- 24042701
TI  - The effect of endurance exercise on both skeletal muscle and systemic oxidative
      stress in previously sedentary obese men.
AB  - BACKGROUND: Obesity is associated with low-grade systemic inflammation, in part
      because of secretion of proinflammatory cytokines, resulting into peripheral
      insulin resistance (IR). Increased oxidative stress is proposed to link adiposity
      and chronic inflammation. The effects of endurance exercise in modulating these
      outcomes in insulin-resistant obese adults remain unclear. We investigated the
      effect of endurance exercise on markers of oxidative damage (4-hydroxy-2-nonenal
      (4-HNE), protein carbonyls (PCs)) and antioxidant enzymes (superoxide dismutase
      (SOD), catalase) in skeletal muscle; urinary markers of oxidative stress (8
      hydroxy-2-deoxyguanosine (8-OHdG), 8-isoprostane); and plasma cytokines (C
      reactive protein (CRP), interleukin-6 (IL-6), leptin, adiponectin). METHODS: Age-
      and fitness-matched sedentary obese and lean men (n=9 per group) underwent 3
      months of moderate-intensity endurance cycling training with a vastus lateralis
      biopsy, 24-h urine sample and venous blood samples taken before and after the
      intervention. RESULTS: Obese subjects had increased levels of oxidative damage: 4
      HNE (+37%; P?0.03) and PC (+63%; P?0.02); evidence of increased adaptive response
      to oxidative stress because of elevated levels of copper/zinc SOD (Cu/ZnSOD)
      protein content (+84%; P?0.01); increased markers of inflammation: CRP (+737%;
      P?0.0001) and IL-6 (+85%; P?0.03), and these correlated with increased markers of
      obesity; and increased leptin (+262%; P?0.0001) with lower adiponectin (-27%;
      P?0.01) levels vs lean controls. Training reduced 4-HNE (-10%; P?0.04), PC (-21%;
      P?0.05), 8-isoprostane (-26%; P?0.02) and leptin levels (-33%; P?0.01); had a
      tendency to decrease IL-6 levels (-21%; P=0.07) and IR (-17%; P=0.10); and
      increased manganese SOD (MnSOD) levels (+47%; P?0.01). CONCLUSION: Endurance
      exercise reduced skeletal muscle-specific and systemic oxidative damage while
      improving IR and cytokine profile associated with obesity, independent of weight
      loss. Hence, exercise is a useful therapeutic modality to reduce risk factors
      associated with the pathogenesis of IR in obesity.

PMID- 24042728
TI  - Discharge education to promote self-management following cardiovascular surgery:
      an integrative review.
AB  - BACKGROUND: Nurses have a key role in teaching cardiovascular (CV) surgical
      patients to manage their post-surgical care after discharge. There is evidence
      that effective patient teaching contributes to improved quality of life,
      decreased anxiety and depression and fewer post-CV surgery emergency department
      visits and hospital readmissions. Despite this, there are no guidelines or
      standards for how best to educate CV surgical patients for discharge. AIM: To
      conduct a literature review of published research on discharge education for CV
      surgical patients to inform guidelines for educating CV surgical patients.
      METHOD: An exhaustive search of CINAHL, Medline, Web of Science, Cochrane
      Database of Systematic Reviews, and ERIC was executed using the following search
      terms: cardiovascular, cardiac, cardio*, heart, surg*, transplant, discharge,
      self-manage*, teach*, educat*, preop*, patient, care. In addition, an ancestry
      search of all reference lists was completed. Studies were included if they were
      published between 2007 and 2012 and focused on preoperative CV surgery adult
      patient education. RESULTS: The search yielded 20 studies, 12 were excluded
      because they did not meet the inclusion/exclusion criteria. Eight studies were
      included in the final review. Three studies reported statistically significant
      decreases in reported anxiety and depression and increased subjective health.
      Four studies had mixed results with both positive and neutral findings. No
      studies reported negative findings in relation to preoperative education.
      CONCLUSION: Patients and staff identified that patient education is essential.
      Standardized educational tools are appropriate as they can spare resources, but
      are only effective if used in conjunction with individualized education.

PMID- 24042702
TI  - Violence and crime among male inpatients with severe mental illness: attempting
      to explain ethnic differences.
AB  - BACKGROUND: Studies report that in the U.K., among men with severe mental illness
      (SMI), those of black Caribbean ethnicity display increased risk of aggressive
      behaviour, criminal convictions, and schizophrenia. The study aimed to compare
      aggressive behaviour and criminal convictions among men with SMI of white
      British, black Caribbean and black African ethnicity, and to explore factors
      associated with differences across ethnicities. METHOD: Sample 1 included 1,104
      male inpatients with SMI. Sample 2 included a representative sub-sample of 165
      who completed interviews, and authorized access to medical and criminal files.
      Ethnicity was self-ascribed. RESULTS: Staff-rated violence prior to admission,
      self-reported aggressive behaviour, and convictions for non-violent and violent
      crimes differed among men with SMI of different ethnicities. Relative to men with
      SMI of white British ethnicity, those of black African ethnicity showed decreased
      risk of aggressive behaviour, and those of black Caribbean ethnicity showed
      elevated risk of convictions for non-violent, and marginally, for violent crimes.
      Relative to men with SMI of black African ethnicity, those of black Caribbean
      ethnicity showed elevated risk of aggressive behaviour and criminal convictions.
      Proportionately more of the men of both black African and black Caribbean
      ethnicity, than those of white British ethnicity, presented schizophrenia
      spectrum disorders. Multivariate analyses failed to identify factors that would
      explain differences in aggressive behaviour, and criminal convictions across
      ethnic groups. CONCLUSIONS: Differences in four different measures of aggressive
      and antisocial behaviour among men with SMI of different ethnicities were
      observed but factors associated with these differences were not found.

PMID- 24042729
TI  - Optimization and establishment of RNA interference-mediated knockdown of the
      progestagen-associated endometrial protein gene in human metastatic melanoma cell
      lines.
AB  - Progestagen-associated endometrial protein (PAEP), also termed glycodelin, is a
      28-kDa glycoprotein of the lipocalin superfamily that is expressed in a variety
      of tumors, including gynecological tumors, lung cancer and melanoma. To determine
      the biological functions of the PAEP gene in tumor development and progression,
      the production of transient and stable PAEP knockdown cell models is required. In
      the present study, RNA interference technology was used to silence PAEP gene
      expression in melanoma and transfection was screened for and the conditions were
      optimized using fluorescence microscopy, flow cytometry, qPCR and western blot
      analysis. The results of the present study showed that the transient transfection
      of melanoma cells with 100 nmol/l PAEP siRNA or lentiviral PAEP small hairpin RNA
      (shRNA) [multiplicity of infection (MOI), 100 pfu/cell] efficiently knocked down
      target gene expression. To establish stable PAEP knockdown cell lines, melanoma
      cells were infected with a low MOI (10 pfu/cell) of lentiviral particles
      expressing PAEP shRNA. Following puromycin screening, the PAEP gene knockdown
      efficiency was demonstrated to be >80% in 624-Mel and 624.38-Mel cell lines,
      which was validated by western blot analysis. Therefore, melanoma cell lines with
      stable knockdown of PAEP were successfully established and may be used as
      effective cell models to study the biological functions of the PAEP gene in
      melanoma.

PMID- 24042730
TI  - From chemistry to mechanics: bulk modulus evolution of Li-Si and Li-Sn alloys via
      the metallic electronegativity scale.
AB  - Toward engineering high performance anode alloys for Li-ion batteries, we
      proposed a useful method to quantitatively estimate the bulk modulus of binary
      alloys in terms of metallic electronegativity (EN), alloy composition and formula
      volume. On the basis of our proposed potential viewpoint, EN as a fundamental
      chemistry concept can be extended to be an important physical parameter to
      characterize the mechanical performance of Li-Si and Li-Sn alloys as anode
      materials for Li-ion batteries. The bulk modulus of binary alloys is linearly
      proportional to the combination of average metallic EN and atomic density of
      alloys. We calculated the bulk moduli of Li-Si and Li-Sn alloys with different Li
      concentrations, which can agree well with the reported data. The bulk modulus of
      Li-Si and Li-Sn alloys decreases with increasing Li concentration, leading to the
      elastic softening of the alloys, which is essentially caused by the decreased
      strength of constituent chemical bonds in alloys from the viewpoint of EN. This
      work provides a deep understanding of mechanical failure of Si and Sn anodes for
      Li-ion batteries, and permits the prediction of the composition dependent bulk
      modulus of various lithiated alloys on the basis of chemical formula, metallic EN
      and cell volume (or alloy density), with no structural details required. 

PMID- 24042731
TI  - Double perovskites as a family of highly active catalysts for oxygen evolution in
      alkaline solution.
AB  - The electronic structure of transition metal oxides governs the catalysis of many
      central reactions for energy storage applications such as oxygen
      electrocatalysis. Here we exploit the versatility of the perovskite structure to
      search for oxide catalysts that are both active and stable. We report double
      perovskites (Ln0.5Ba0.5)CoO(3-delta) (Ln=Pr, Sm, Gd and Ho) as a family of highly
      active catalysts for the oxygen evolution reaction upon water oxidation in
      alkaline solution. These double perovskites are stable unlike pseudocubic
      perovskites with comparable activities such as Ba0.5Sr0.5Co0.8Fe0.2O(3-delta)
      which readily amorphize during the oxygen evolution reaction. The high activity
      and stability of these double perovskites can be explained by having the O p-band
      centre neither too close nor too far from the Fermi level, which is computed from
      ab initio studies.

PMID- 24042733
TI  - How primary care practices can improve continuity of care.

PMID- 24042732
TI  - Prevalence and risk factors for hypertension and association with ethnicity in
      Nigeria: results from a national survey.
AB  - OBJECTIVE: Non-communicable diseases are now a global priority. We report on the
      prevalence of hypertension and its risk factors, including ethnicity, in a
      nationally representative sample of Nigerian adults recruited to a survey of
      visual impairment. METHODS: multi-stage, stratified, cluster random sample with
      probability proportional to size procedures was used to obtain a nationally
      representative sample of 13 591 subjects aged >= 40 years. Of these, 13 504
      (99.4%) had a blood pressure measurement. RESULTS: The prevalence of hypertension
      was 44.9% [95% confidence interval (CI): 43.5-46.3% ]. Increasing age, gender,
      urban residence and body mass index were independent risk factors (p < 0.001).
      The Kanuri ethnic group had the highest prevalence of hypertension (77.5%, 95%
      CI: 71.0-84.0%). CONCLUSIONS: The high prevalence of hypertension in Nigeria is a
      cause for concern and suggests that it is inevitable that the impact of
      hypertension-related ill health is imminent, with the accompanying financial and
      societal costs to families and the state of Nigeria.

PMID- 24042734
TI  - Protooncogene TCL1b functions as an Akt kinase co-activator that exhibits
      oncogenic potency in vivo.
AB  - Protooncogene T-cell leukemia 1 (TCL1), which is implicated in human T-cell
      prolymphocytic leukemia (T-PLL), interacts with Akt and enhances its kinase
      activity, functioning as an Akt kinase co-activator. Two major isoforms of TCL1
      Protooncogenes (TCL1 and TCL1b) are present adjacent to each other on human
      chromosome 14q.32. In human T-PLL, both TCL1 and TCL1b are activated by
      chromosomal translocation. Moreover, TCL1b-transgenic mice have never been
      created. Therefore, it remains unclear whether TCL1b itself, independent of TCL1,
      exhibits oncogenicity. In co-immunoprecipitation assays, both ectopic and
      endogenous TCL1b interacted with Akt. In in vitro Akt kinase assays, TCL1b
      enhanced Akt kinase activity in dose- and time-dependent manners. Bioinformatics
      approaches utilizing multiregression analysis, cluster analysis, KEGG (Kyoto
      Encyclopedia of Genes and Genomes) pathway mapping, Venn diagrams and Gene
      Ontology (GO) demonstrated that TCL1b showed highly homologous gene-induction
      signatures similar to Myr-Akt or TCL1. TCL1b exhibited oncogenicity in in vitro
      colony-transformation assay. Further, two independent lines of beta-actin
      promoter-driven TCL1b-transgenic mice developed angiosarcoma on the intestinal
      tract. Angiosarcoma is a rare form of cancer in humans with poor prognosis. Using
      immunohistochemistry, 11 out of 13 human angiosarcoma samples were positively
      stained with both anti-TCL1b and anti-phospho-Akt antibodies. Consistently, in
      various cancer tissues, 69 out of 146 samples were positively stained with anti
      TCL1b, out of which 46 were positively stained with anti-phospho-Akt antibodies.
      Moreover, TCL1b structure-based inhibitor 'TCL1b-Akt-in' inhibited Akt kinase
      activity in in vitro kinase assays and PDGF (platelet-derived growth factor)
      induced Akt kinase activities-in turn, 'TCL1b-Akt-in' inhibited cellular
      proliferation of sarcoma. The current study disclosed TCL1b bears oncogenicity
      and hence serves as a novel therapeutic target for human neoplastic diseases. 

PMID- 24042735
TI  - Epigenetic and genetic features of 24 colon cancer cell lines.
AB  - Cell lines are invaluable biomedical research tools, and recent literature has
      emphasized the importance of genotype authentication and characterization. In the
      present study, 24 out of 27 cell line identities were confirmed by short tandem
      repeat profiling. The molecular phenotypes of the 24 colon cancer cell lines were
      examined, and microsatellite instability (MSI) and CpG island methylator
      phenotype (CIMP) were determined, using the Bethesda panel mononucleotide repeat
      loci and two epimarker panels, respectively. Furthermore, the BRAF, KRAS and
      PIK3CA oncogenes were analyzed for mutations in known hotspots, while the entire
      coding sequences of the PTEN and TP53 tumor suppressors were investigated. Nine
      cell lines showed MSI. Thirteen and nine cell lines were found to be CIMP
      positive, using the Issa panel and the Weisenberger et al. panel, respectively.
      The latter was found to be superior for CIMP classification of colon cancer cell
      lines. Seventeen cell lines harbored disrupting TP53 mutations. Altogether, 20/24
      cell lines had the mitogen-activated protein kinase pathway activating mutually
      exclusive KRAS or BRAF mutations. PIK3CA and PTEN mutations leading to
      hyperactivation of the phosphoinositide 3-kinase/AKT pathway were observed in
      13/24 cell lines. Interestingly, in four cell lines there were no mutations in
      neither BRAF, KRAS, PIK3CA nor in PTEN. In conclusion, this study presents
      molecular features of a large number of colon cancer cell lines to aid the
      selection of suitable in vitro models for descriptive and functional research. 

PMID- 24042736
TI  - Systematic fluoroscopic and electrical assessment of implantable cardioverter
      defibrillator patients implanted with silicone-polyurethane copolymer (OptimTM)
      coated leads.
AB  - AIMS: Serious concerns have been recently raised about the reliability of the
      silicone-polyurethane copolymer (OptimTM) lead insulation system. We sought to
      identify insulation defects and Optim-lead failures by systematic fluoroscopic
      and electrical assessment in a prospectively defined cohort of implantable
      cardioverter-defibrillator (ICD) patients. METHODS AND RESULTS: Between July 2007
      and December 2011, 234 patients were implanted with 413 optim-coated leads as
      part of an ICD system at a single centre. Fluoroscopic screening with high
      resolution cine-fluoroscopy at 30 frames per second was offered to all patients.
      In addition, the electrical integrity of all implanted leads was assessed.
      Durata, Riata ST Optim, and low-voltage Optim leads were implanted in 199, 26,
      and 188 cases, respectively. During a total follow-up of 10 036 lead-months,
      there were 7 Optim-lead failures (defined as electrical malfunction resulting in
      lead replacement) and 31 deaths; no cases of electrical noises were encountered.
      The overall incidence of lead failure was 1.2 vs. 0.3 per 100 lead-years, for
      high- and low-voltage leads, respectively (P = 0.1). One hundred fifty-one
      patients agreed to undergo fluoroscopy screening; none of the 264 analysed Optim
      leads were found to have any fluoroscopically visible structural defects after an
      average of 31 months post-implant. CONCLUSION: This study represents the first
      systematic screening of Optim-coated leads in a large unselected cohort of ICD
      patients. Over a 5-year period few lead failures were observed and normal
      fluoroscopic appearance was present in all patients.

PMID- 24042737
TI  - Genital beautification: a concept that offers more than reduction of the labia
      minora.
AB  - BACKGROUND: The interest and demand for female genital rejuvenation surgery are
      steadily increasing. This report presents a concept of genital beautification
      consisting of labia minora reduction, labia majora augmentation by autologous fat
      transplantation, labial brightening by laser, mons pubis reduction by
      liposuction, and vaginal tightening if desired. METHODS: Genital beautification
      was performed for 124 patients between May 2009 and January 2012 and followed up
      for 1 year to obtain data about satisfaction with the surgery. RESULTS: Of the
      124 female patients included in the study, 118 (95.2 %) were happy and 4 (3.2 %)
      were very happy with their postoperative appearance. In terms of postoperative
      functionality, 84 patients (67.7 %) were happy and 40 (32.3 %) were very happy.
      Only 2 patients (1.6 %) were not satisfied with the aesthetic result of their
      genital beautification procedures, and 10 patients (8.1 %) experienced wound
      dehiscence. CONCLUSION: The described technique of genital beautification
      combines different aesthetic female genital surgery techniques. Like other
      aesthetic surgeries, these procedures are designed for the subjective improvement
      of the appearance and feelings of the patients. The effects of the operation are
      functional and psychological. They offer the opportunity for sexual stimulation
      and satisfaction. The complication rate is low. Superior aesthetic results and
      patient satisfaction can be achieved by applying this technique. 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- 24042738
TI  - Monitored Water Vapour Barrier Coatings for Flexible Micro-Implants.

PMID- 24042739
TI  - Solving Biocompatibility Layer by Layer: Designing Scaffolds for Tissues.

PMID- 24042740
TI  - Coating Thickness Determination on Drug-Eluting Stents - Comparison of Methods.

PMID- 24042741
TI  - Stability Analysis Of Superparamagnetic Iron Oxide Nanoparticles (Spions) At 37 
      degrees C.

PMID- 24042742
TI  - Influence of Shot Peening on Surface Roughness and Invitro Load Cycles of
      Magnesium Alloys.

PMID- 24042743
TI  - Ceramic-on-ceramic material pairings under simplified knee replacement conditions
      show increasing wear with increasing conformity.

PMID- 24042744
TI  - Dynamic Hysteresis Behaviour of Respiratory System Mechanics.

PMID- 24042745
TI  - Outcome of 23h Bracing for Tip-toe-walking Children with Cerebral Palsy.

PMID- 24042746
TI  - The Analysis of Lung Mechanics of Ventilated Patients During Elective Surgical
      Procedure Indicated Intratidal Recruitment.

PMID- 24042747
TI  - The Impact of Design Modifications on the Mechanical Properties of a Polymeric
      Slotted Tube Coronary Stent.

PMID- 24042748
TI  - Image-guided failure assessment of human trabecular bone - Inverse finite element
      modelling for characterization of elastic properties.

PMID- 24042749
TI  - Determination of Mechanical and Microstructural Tissue Quantities for Modeling
      Damage in Arterial Tissues.

PMID- 24042750
TI  - Biomechanical Characterisation of Scaffold-Free Cartilage Constructs with
      Hyperelastic Material Models.

PMID- 24042751
TI  - Evaluation of Biomechanical Models for the Planning of Total Hip Arthroplasty.

PMID- 24042752
TI  - Finite Element Analysis of Compliance of Stent-Vesselsystems.

PMID- 24042753
TI  - A Mobile Gait Analysis System for Optimization of Prosthetic Alignments.

PMID- 24042754
TI  - The shape of intratidal resistance-volume and compliance-volume curves in
      mechanical ventilation - an animal study.

PMID- 24042755
TI  - Biomechanics of Optimum Stent Implantation Strategy Considering Vessel Wall
      Contact and Vessel Trauma.

PMID- 24042756
TI  - Biomechanical Properties of the Human Ventricular Myocardium.

PMID- 24042757
TI  - The Q-Angle and its Effect on Active Knee Joint Kinematics - a Simulation Study.

PMID- 24042758
TI  - Material Modeling of the Damage Behavior of Arterial Tissues.

PMID- 24042759
TI  - Posturographic Assessment of Increased Fall Risk.

PMID- 24042760
TI  - A Novel Magnetic Field Device for Inducing Hyperthermia Using Magnetic
      Nanoparticles.

PMID- 24042761
TI  - Long-Term Validation of a Blood Pressure Sensor at the Chest.

PMID- 24042762
TI  - Certified dOFM sampling devices provide access to target tissue in pharmaceutical
      trials.

PMID- 24042763
TI  - In-Ear Pulse Wave Measurements: A Pilot Study.

PMID- 24042764
TI  - Magnetoencephalography of Deep Lying Auditory Sources Using Acoustical Devices
      for Infra- and Ultrasound Stimulation.

PMID- 24042765
TI  - Characterization of Unfocused / Weakly Focused Pressure Pulse Sources for
      Extracorporeal Pain Therapy ("Radial Shock Wave Therapy" Sources).

PMID- 24042766
TI  - Experiences with Pulse Arrival Time as Surrogate for Systolic Blood Pressure.

PMID- 24042767
TI  - Microwave Doppler Radar for Cardiac and Respiratory Activity Measurement -
      Preliminary Results.

PMID- 24042768
TI  - Non-Interfering Cardiovascular Diagnostics and Blood Pressure.

PMID- 24042769
TI  - Development of a Pulseoximeter to Measure the Oxygen Saturation and the Heartrate
      of Sedated Mice.

PMID- 24042770
TI  - Continuous Wrist Blood Pressure Measurement with Ultrasound.

PMID- 24042771
TI  - New Dry Electrodes with Comparable Performance as Standard Electrodes.

PMID- 24042773
TI  - Improving Sensor Surface Properties by Chitosan Coating.

PMID- 24042772
TI  - Customized electrical impedance tomography based analysis of regional lung
      function: a feasibility study.

PMID- 24042774
TI  - Diagnostic Lab-on-a-Chip System Based on Fluorescence Imaging and Integrating
      Sample Preparation.

PMID- 24042775
TI  - Comparison of Elisa Sensitivity Relating to Manual and Low-Pressure Loading of
      the Fluidic Test Device.

PMID- 24042776
TI  - Single-port glucose monitoring with simultaneous insulin infusion.

PMID- 24042777
TI  - Point-of-Care Chip for Diagnosis of Sepsis: Joining Biomarker Quantification and
      Bacterial Class Identification.

PMID- 24042778
TI  - Capacitive transducers as platform for smart hydrogels.

PMID- 24042779
TI  - Foldable polymer patches with implemented pressure sensors.

PMID- 24042780
TI  - In Vivo Investigations on Anti-Fouling Hydrogel Coatings.

PMID- 24042781
TI  - icath - Integrated Catheter for Simultaneous Glucose Measurement and Insulin
      Infusion.

PMID- 24042782
TI  - Sensor for early detection of wound infection.

PMID- 24042783
TI  - Optimising the glucose sampling performance of an intravascular
      microdialysisbased continuous glucose monitoring device for use in hospital
      settings.

PMID- 24042784
TI  - Design and evaluation of a microfluidic-based whole blood pre-treatment module to
      detect folic acid.

PMID- 24042785
TI  - Test Environment for Hydrogels as Functional Sensor Window.

PMID- 24042786
TI  - Phenomenological analysis of magnetic nanoparticle size distributions with
      temperature dependent magnetorelaxometry.

PMID- 24042787
TI  - Integrated Smart Systems for Theranostic Applications.

PMID- 24042788
TI  - Magnetic Particle Spectroscopy for the Quantification of Magnetic Nanoparticles
      in Living Cells.

PMID- 24042789
TI  - Electronic nose detects heart failure from exhaled breath.

PMID- 24042790
TI  - An Automatic Algorithm for the Detection of Periodic Leg Movements.

PMID- 24042791
TI  - Panel Discussion: Interoperability of Toolboxes - A Useful Second Level Aim ?

PMID- 24042792
TI  - Interrelation of Cardiovascular Dysfunction and Pupillary Fluctuations in
      Patients with Major Depression.

PMID- 24042793
TI  - EEG Measures Indicating Anaesthesia Induced Changes of Cortical Information
      Processing.

PMID- 24042794
TI  - Local Regularization in the Inverse Problem of Electrocardiography.

PMID- 24042795
TI  - Stimfit: A Fast Visualization and Analysis Environment for Cellular
      Neurophysiology.

PMID- 24042796
TI  - Spike Sorting Algorithm for Multichannel MEA Recordings Based on Cross
      Correlation.

PMID- 24042797
TI  - Real-Time Software for Functional Mapping of Eloquent Cortex Using
      Electrocorticography.

PMID- 24042798
TI  - T Wave Morphology during Heart Rate Turbulence in Patients with Chronic Heart
      Failure.

PMID- 24042799
TI  - Determining Blood Pressure Changes and Vascular Stiffness State Using Optical
      Pulse Pressure Analysis.

PMID- 24042800
TI  - Short-Term EEG Patterns of Driver Drowsiness and their Relation to Crashes.

PMID- 24042801
TI  - Openwalnut: An Open-Source Tool for Visualization of Medical and Bio-Signal Data.

PMID- 24042802
TI  - EEG Controlled Ni Lego Robot: Feasibility Study of Sensorimotor Alpha Rhythm
      Neurofeedback in Children.

PMID- 24042803
TI  - Detection of Multiple Pacemaker Centers in Cardiomyocyte Cell Layers for
      Estimating Wavefront Propagation Patterns.

PMID- 24042804
TI  - Electrode Arrangements for ECG Imaging under Practical Constraints of a Catheter
      Lab Setting.

PMID- 24042805
TI  - Generating Biatrial Local Activation Time Maps Using the Non-Linear Energy
      Operator Reveals Arrhythmia.

PMID- 24042806
TI  - A Novel Method for Motion Artifact Removal in Wearable PPG Sensors Based on Blind
      Source Separation.

PMID- 24042807
TI  - Correction of Eye-Movement Artifacts of DC-EEG Signals.

PMID- 24042808
TI  - Evaluating Changes in Electrogram Morphology during Radiofrequency Ablation of
      Cardiac Arrhythmias.

PMID- 24042809
TI  - TOCSY - Toolboxes for modelling of dynamical systems and time series.

PMID- 24042810
TI  - PCA-Based ECG Lead Reconstruction.

PMID- 24042811
TI  - A Wearable Device for Realtime Assessment of Vigilance.

PMID- 24042812
TI  - Analytic Signal Based Detection of Extracellular Action Potentials.

PMID- 24042813
TI  - Quantification of heart beat nonstationarities by nonparametric segmentation.

PMID- 24042814
TI  - Analysis of Dynamic Respiratory Mechanics Profits from Breathing-Phase Selective
      Filtering.

PMID- 24042815
TI  - Motion artefact detection in capacitively coupled EEG recording.

PMID- 24042817
TI  - High-Level Feature Extraction from Electrophysiological Brain Signals in the Time
      Frequency Domain.

PMID- 24042816
TI  - Eeglab - an Open Source Matlab Toolbox for Electrophysiological Research.

PMID- 24042818
TI  - A System for Online Neuroelectromagnetic Source Imaging.

PMID- 24042819
TI  - Ventrikulare Desynchronisation mit und ohne Ischamische Herzerkrankung bei
      Resynchronisationsrespondern.

PMID- 24042820
TI  - Comparison of pediatric ECG from digital devices or scanned images.

PMID- 24042821
TI  - Exploring Effective Connectivity by a Granger Causality Approach with Embedded
      Dimension Reduction.

PMID- 24042822
TI  - A New Normalised Short Time PDC for Dynamic Coupling Analyses.

PMID- 24042823
TI  - Mne-X: MEG/EEG Real-Time Acquisition, Real-Time Processing, and Real-Time Source
      Localization Framework.

PMID- 24042824
TI  - Circular Correlation Coefficients versus the Phase-Locking-Value.

PMID- 24042825
TI  - CNAP - Evolution of Continuous Non-Invasive Arterial Blood Pressure Monitoring.

PMID- 24042826
TI  - Computing Lead-Field Matrices for a Body Tissue Conductivity Range.

PMID- 24042827
TI  - Fall Detector with Random Classifier Optimization.

PMID- 24042828
TI  - Correlation between autonomic dysfunction and impaired microcirculation in
      patients with schizophrenia.

PMID- 24042829
TI  - A General Approach for Dynamic Modeling of Physiological Time Series.

PMID- 24042830
TI  - Sigviewer and Signalserver - Open Source Software Projects for Biosignal
      Analysis.

PMID- 24042831
TI  - Automatic Validation and Quality Based Readjustment of Manually Scored EEG
      Arousal.

PMID- 24042832
TI  - Transosophageales Interventrikulares Delay bei Vorhofflimmern und Kardialer
      Resynchronisation.

PMID- 24042833
TI  - Subviral Particle Tracking.

PMID- 24042834
TI  - Textile Reinforcement in Fibrin-based Tissue Engineerd Heart Valves.

PMID- 24042835
TI  - Poly-Ionic Liquids as New Hydrogel Materials: Synthesis, Characterization and
      Application.

PMID- 24042836
TI  - Mechanical properties of human lung cells after mechanostimulation.

PMID- 24042837
TI  - Analysis of glucose and fetal calf serum in aqueous solution for Multi Organ
      Tissue Flow (MOTiF) bioreactors using NIR Spectroscopy.

PMID- 24042838
TI  - High-glucose-based peritoneal dialysis solution induces the upregulation of VEGF
      expression in human peritoneal mesothelial cells: The role of pleiotrophin.
AB  - The aim of the present study was to investigate the effect of a high-glucose
      based peritoneal dialysis solution (HGPDS) on the expression of pleiotrophin
      (PTN) and vascular endothelial growth factor (VEGF) in human peritoneal
      mesothelial cells (HPMCs) and the mechanisms through which fluvastatin (Flu)
      protects the peritoneal membrane in continuous ambulatory peritoneal dialysis
      (CAPD). HPMCs were cultured with HGPDS, Flu (10-8-10-6 mol/l) and PTN (10-30
      nmol/l). The expression of PTN and VEGF was examined at the mRNA and protein
      level. To define the role of PTN in the regulation of VEGF expression, HPMCs were
      cultured with HGPDS in the presence or absence of the blocking peptide of PTN.
      The signaling pathways involved in PTN synthesis induced by HGPDS were also
      characterized. The phenotypic characteristics of HPMCs were observed under a
      light microscope. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) colorimetry and the mRNA and protein expression
      of PTN, VEGF and ERK1/2 was assessed by RT-PCR and the western blot analysis,
      respectively. Following incubation with HGPDS for 48 h, the morphology of the
      HPMCs changed from a typical cobblestone-like appearance to a fibroblast-like
      phenotype. The same alteration in the morphology of the HPMCs also occurred
      following incubation with 20 nmol/l PTN. Flu (10-6 mol/l), GSK650394 [a
      competitive inhibitor of serum/glucocorticoid-regulated kinase 1 (SGK1), 10-5
      mol/l] and PD98059 (a competitive inhibitor of ERK1/2, 10-5 mol/l) improved the
      negative changes in cell morphology induced by HGPDS. The results of MTT assay
      revealed that the reduction in HPMC viability occurred in the groups treated with
      HGPDS and this reduction was partially restored by Flu, GSK650394 and PD98059. A
      significant improvement in cell viability, which had been decreased by HGPDS, was
      observed following treatment with Flu (10-6 mol/l), PD98059 (10-5 mol/l) or
      GSK650394 (10-5 mol/l) (P<0.05). Compared with the control, the mRNA and protein
      expression of PTN and VEGF significantly increased in the HPMCs treated with
      HGPDS (P<0.05). GSK650394 and PD98059 significantly decreased the high mRNA and
      protein expression levels of PTN and VEGF induced by HGPDS (P<0.05) and Flu had
      the same inhibitory effect as GSK650394 and PD98059 in a dose-dependent manner
      (P<0.05). The mRNA and protein expression of VEGF increased following the
      incubation of HPMCs with 20 nmol/l PTN. By contrast, the mRNA and protein
      expression levels of VEGF in the HPMCs decreased in the presence of the blocking
      peptide of PTN. The results from the present study indicated that HGPDS increased
      the expression of PTN and VEGF in the HPMCs, and this increase was attenuated by
      Flu, GSK650394 and PD98059. The protein expression of phosphorylated ERK1/2 (p
      ERK1/2) was decreased by GSK650394 in the HPMCs treated with HGPDS. Taken
      together, the protective effects of Flu in HPMCs may be partially achieved
      through the SGK1-ERK1/2 signaling pathway.

PMID- 24042839
TI  - Histological alterations on the structure of the excretory renal system in tench
      (Tinca tinca) after exposure to 17-alpha-ethynylestradiol.
AB  - This study describes the effects of 17-alpha-ethynylestradiol (EE2) on the
      structure of the excretory system of the kidney in tench. Adult male tench were
      exposed to sub-lethal doses of EE2 (50, 100 and 500 MUg/kg b.w.) under semistatic
      conditions for a period of 30 days. The nephrosomatic index and histology
      (including a morphometric analysis) of the kidney were examined.
      Histopathological lesions in the kidney of exposed tench were: dilation of
      glomerular capillaries and increase in the area of the renal corpuscle, hyaline
      degeneration in the epithelial cells of the proximal tubules leading to necrotic
      changes, hemorrhages in the interstitial tissue and deposits of eosinophilic
      material. These lesions were observed with a greater degree of severity as the
      exposure doses were increased. These results indicate that long-term exposure to
      EE2 could produce clear negative effects on the excretory system of the kidney in
      tench and consequently on their physiological functions. 

PMID- 24042840
TI  - Effects of di-n-butyl phthalate and diethyl phthalate on acetylcholinesterase
      activity and neurotoxicity related gene expression in embryonic zebrafish.
AB  - In the present study, zebrafish embryos were used to assess the neurotoxicity of
      di-n-butyl phthalate (DBP), diethyl phthalate (DEP) and their mixture. Four-hour
      post-fertilization (hpf) zebrafish embryos were exposed to various concentrations
      of DBP, DEP and their mixture (DBP-DEP) until 96 hpf. The transcriptions levels
      of selected neuron-related genes reported as neurotoxicity biomarkers were
      analyzed. The results showed that transcripts of growth associated protein 43
      (gap43), embryonic lethal abnormal vision-like 3 (elavl3), glial fibrillary
      acidic protein (gfap), myelin basic protein (mbp), alpha1-tubulin and neurogenin1
      (ngn1) were significantly up-regulated after DBP, DEP and DBP-DEP mixture
      exposure. In addition, acetylcholinesterase activity was significantly inhibited
      in the embryos. These results indicate that DBP and DEP have the potential
      neurotoxicity in zebrafish embryos. 

PMID- 24042841
TI  - Occurrence of higher chlorinated benzenes in livers of grass carp and common carp
      collected from markets of Xinxiang, China.
AB  - Five higher chlorinated benzenes (including hexachlorobenzene (HCB),
      pentachlorobenzene (PeCB) and three isomers of tetrachlorobenzens) were measured
      in the livers of grass carp and common carp collected from five markets in
      Xinxiang city, China. HCB and PeCB were detected in all samples. The major
      component of the higher CBs residue was HCB and significant correlations existed
      between HCB and PeCB in both grass carp and common carp livers. The ratio range
      of HCB/PeCB in grass carp and common carp were 3.4-6.2 and 4.9-7.7, respectively,
      which implied the sources of higher CBs originate mainly from the
      revolatilization of industrial HCB with a minor impact from PeCB.

PMID- 24042842
TI  - Mutagenicity and genotoxicity in gill erythrocyte cells of Poecilia reticulata
      exposed to a glyphosate formulation.
AB  - Poecilia reticulata were exposed to herbicide Roundup Transorb((r)) for
      micronucleus test, nuclear abnormalities and comet assay. The exposure
      concentrations were based on CL50-96 h following 0, 1.41, 2.83, 4.24 and 5.65 MUL
      L(-1) for 24 h. Micronucleus and comets were significantly increased in the gill
      erythrocyte cells after herbicide exposure compared with the non-exposed group.
      Results showed a gradual increase in the number of damaged cells, indicating a
      concentration-dependent effect and that this herbicide was mutagenic and
      genotoxic to P. reticulata and this effect could be attributed to a combination
      of compounds contained in the formulation with the active ingredient glyphosate.

PMID- 24042843
TI  - Biological Fenton's oxidation of pentachlorophenol by aquatic plants.
AB  - This study proposes a new treatment method to decompose persistent chemicals such
      as pentachlorophenol (PCP) in water, utilizing hydrogen peroxide present in
      aquatic plants to proceed the biological Fenton reaction. PCP was not effectively
      removed by aquatic plants. However, by adding 2.8 mM of Fe(2+), there was a rapid
      removal of PCP while at the same time consumption of endogenous hydrogen peroxide
      occurred. It was observed the increase of chloride ions formation in water
      confirming the complete degradation of PCP. These results demonstrated that PCP
      was oxidized through a biological Fenton reaction, and hydrogen peroxide in
      aquatic plants was a key endogenous substance in treatment of refractory toxic
      pollutants. 

PMID- 24042845
TI  - An oncolytic adenovirus expressing interleukin-24 enhances antitumor activities
      in combination with paclitaxel in breast cancer cells.
AB  - Oncolytic adenoviruses are a novel class of anticancer treatment, based upon
      their ability to replicate selectively within malignant cells resulting in cell
      lysis. The replication-selective adenovirus, ZD55-IL-24, was constructed by
      harboring an E1B-55 kDa deletion and arming with interleukin-24 (IL-24). The
      microtubule-stabilizing drug paclitaxel (PTX) exhibits activity in relapsed
      cancer. In the present study, the synergistic antitumor effects of the
      combination of PTX and ZD55-IL-24 on breast cancer cells was investigated. The
      results demonstrated that there were different roles for PTX in the expression of
      transgenic mRNA and protein. ZD55-IL-24 combined with PTX induced marked growth
      inhibition of MDA-MB-231 and Bcap-37 cells. PTX increased viral uptake and
      appeared not to alter the replication of ZD55-IL-24 in breast cancer cells.
      Annexin V-fluorescein isothiocyanate/propidium iodide staining and the Hoechst
      33258 assay indicated that ZD55-IL-24 induced an increase in the number of
      apoptotic cells when administered in combination with PTX. It was demonstrated
      that ZD55-IL-24 conjugated with PTX was highly concomitant, and increased
      proapoptotic proteins levels, activated caspase-3, -7 and -9 and downregulated
      anti-apoptotic proteins. These results suggested that ZD55-IL-24 in combination
      with PTX exhibited a markedly increased cytotoxic and apoptosis-inducing effect
      in breast cancer cells. Thus, this chemo-gene-viro therapeutic strategy was
      demonstrated to be superior to conventional chemotherapy or gene-viro therapy
      alone.

PMID- 24042846
TI  - Auditory brainstem implantation improves speech recognition in neurofibromatosis
      type II patients.
AB  - This prospective study aimed to determine speech understanding in
      neurofibromatosis type II (NF2) patients following implantation of a MED-EL COMBI
      40+ auditory brainstem implant (ABI). Patients (n = 32) were enrolled
      postsurgically. Nonauditory side effects were evaluated at fitting and
      audiological performance was determined using the Sound Effects Recognition Test
      (SERT), Monosyllable-Trochee-Polysyllable (MTP) test and open-set sentence tests.
      Subjective benefits were determined by questionnaire. ABI activation was
      documented in 27 patients, 2 patients were too ill for testing and 3 patients
      were without any auditory perception. SERT and MTP outcomes under auditory-only
      conditions improved significantly between first fitting and 12-month follow-up.
      Open-set sentence recognition improved from 5% at first fitting to 37% after 12
      months. The number of active electrodes had no significant effect on performance.
      All questionnaire respondents were 'satisfied' to 'very satisfied' with their
      ABI. An ABI is an effective treatment option in NF2 patients with the potential
      to provide open-set speech recognition and subjective benefits. To our knowledge,
      the data presented herein is exceptional in terms of the open-set speech
      perception achieved in NF2 patients.

PMID- 24042847
TI  - Photooxidation of ethanol and 2-propanol on TiO2(110): evidence for methyl
      radical ejection.
AB  - The photooxidation of ethanol and 2-propanol was studied under UHV conditions on
      a single crystal TiO2(110) surface using a combination of temperature programmed
      desorption (TPD) and pump-probe laser ionization techniques. Previous studies of
      these reactions have shown that the first step involves photocatalytic
      dehydrogenation to either an acetaldehyde or acetone intermediate. In this work,
      we show that when adsorbed alcohols are irradiated with UV light in the presence
      of molecular oxygen, methyl radicals are ejected from the surface. Furthermore,
      it is shown that these radicals possess kinetic energy distributions which are
      remarkably similar to those measured for the photooxidation of acetaldehyde and
      acetone. This result suggests that methyl radicals are produced during a second
      photocatalytic step which involves photooxidation of the aldehyde/ketone
      intermediates. 

PMID- 24042848
TI  - A recollection of mTOR signaling in learning and memory.
AB  - Mechanistic target of rapamcyin (mTOR) is a central player in cell growth
      throughout the organism. However, mTOR takes on an additional, more specialized
      role in the developed neuron, where it regulates the protein synthesis-dependent,
      plastic changes underlying learning and memory. mTOR is sequestered in two
      multiprotein complexes (mTORC1 and mTORC2) that have different substrate
      specificities, thus allowing for distinct functions at synapses. We will examine
      how learning activates the mTOR complexes, survey the critical effectors of this
      pathway in the context of synaptic plasticity, and assess whether mTOR plays an
      instructive or permissive role in generating molecular memory traces. 

PMID- 24042850
TI  - The roles of protein kinases in learning and memory.
AB  - In the adult mammalian brain, more than 250 protein kinases are expressed, but
      only a few of these kinases are currently known to enable learning and memory.
      Based on this information it appears that learning and memory-related kinases
      either impact on synaptic transmission by altering ion channel properties or ion
      channel density, or regulate gene expression and protein synthesis causing
      structural changes at existing synapses as well as synaptogenesis. Here, we
      review the roles of these kinases in short-term memory formation, memory
      consolidation, memory storage, retrieval, reconsolidation, and extinction.
      Specifically, we discuss the roles of calcium/calmodulin-dependent kinase II
      (CaMKII), the calcium/calmodulin kinase cascade, extracellular signal regulated
      kinase 1 and 2 (ERK1/2), cAMP-dependent protein kinase A (PKA), cGMP-dependent
      protein kinase G (PKG), the phosphatidylinositol 3-kinase (PI3K) pathway, and
      protein kinase M zeta (PKMzeta). Although these kinases are important for
      learning and memory processes, much remains to be learned as to how they act.
      Therefore, it will be important to identify and characterize the critical
      phosphorylation substrates so that a sophisticated understanding of learning and
      memory processes will be achieved. This will also allow for a systematic analysis
      of dysfunctional kinase activity in mental disorders. 

PMID- 24042851
TI  - New methods for understanding systems consolidation.
AB  - According to the standard model of systems consolidation (SMC), neocortical
      circuits are reactivated during the retrieval of declarative memories. This
      process initially requires the hippocampus. However, with the passage of time,
      neocortical circuits become strengthened and can eventually retrieve memory
      without input from the hippocampus. Although consistent with lesion data, these
      assumptions have been difficult to confirm experimentally. In the current review,
      we discuss recent methodological advances in behavioral neuroscience that are
      making it possible to test the basic assumptions of SMC for the first time. For
      example, new transgenic mice can be used to monitor the activity of individual
      neurons across the entire brain while optogenetic approaches provide precise
      control over the activity of these cells using light stimulation. These tools can
      be used to examine the reactivation of neocortical neurons during recent and
      remote memory retrieval and determine if this process requires the hippocampus. 

PMID- 24042852
TI  - Cadmium iodide-mediated allenylation of terminal alkynes with ketones.
AB  - Allenes are important building blocks in organic synthesis and have attracted
      much attention from researchers worldwide. So far, mono- and 1,3-disubstituted
      allenes can be prepared easily by applying the allenylation of terminal alkynes
      reaction of aldehydes. However, trisubstituted allenes have never been reported
      using this reaction due to the extremely low reactivity of ketones. Here, we
      report the one-pot synthesis of trisubstituted allenes from terminal alkynes and
      ketones utilizing cadmium iodide as the mediator. With this protocol, a series of
      different allenes, including 1,5-bisallenes and optically active allenols, which
      are especially important in synthetic chemistry, have been successfully prepared.

PMID- 24042849
TI  - Growth factor signaling and memory formation: temporal and spatial integration of
      a molecular network.
AB  - Growth factor (GF) signaling is critically important for developmental
      plasticity. It also plays a crucial role in adult plasticity, such as that
      required for memory formation. Although different GFs interact with receptors
      containing distinct types of kinase domains, they typically signal through
      converging intracellular cascades (e.g., Ras-MEK-MAPK) to mediate overlapping
      functional endpoints. Several GFs have been implicated in memory formation, but
      due to a high level of convergent signaling, the unique contributions of
      individual GFs as well as the interactions between GF signaling cascades during
      the induction of memory is not well known. In this review, we highlight the
      unique roles of specific GFs in dendritic plasticity, and discuss the spatial and
      temporal profiles of different GFs during memory formation. Collectively, the
      data suggest that the roles of GF signaling in long-lasting behavioral and
      structural plasticity may be best viewed as interactive components in a complex
      molecular network. 

PMID- 24042853
TI  - The incidence of coronary anomalies on routine coronary computed tomography
      scans.
AB  - OBJECTIVE: This study aimed to assess the incidence of coronary anomalies using
      64-multi-slice coronary computed tomography (MSCT). METHODS: The diagnostic MSCT
      scans of 745 consecutive patients were reviewed. RESULTS: The incidence of
      coronary anomalies was 4.96%. The detected coronary anomalies included the conus
      artery originating separately from the right coronary sinus (RCS) (n = 8, 1.07%),
      absence of the left main artery (n = 7, 0.93%), a superior right coronary artery
      (RCA) (n = 7, 0.93%), the circumflex artery (CFX) arising from the RCS (n = 4,
      0.53%), the CFX originating from the RCA (n = 2, 0.26%), a posterior RCA (n = 1,
      0.13%), a coronary fistula from the left anterior descending artery and RCA to
      the pulmonary artery (n = 1, 0.13%), and a coronary aneurysm (n = 1, 0.13%).
      CONCLUSIONS: This study indicated that MSCT can be used to detect common coronary
      anomalies, and shows it has the potential to aid cardiologists and cardiac
      surgeons by revealing the origin and course of the coronary vessels.

PMID- 24042854
TI  - Tanshinone IIA inhibits human prostate cancer cells growth by induction of
      endoplasmic reticulum stress in vitro and in vivo.
AB  - BACKGROUND: Tanshinone IIA (Tan-IIA) is one of the major lipophilic components
      isolated from the root of Salviae Miltiorrhizae Radix. We explored the mechanisms
      of cell death induced by Tan-IIA treatment in prostate cancer cells in vitro and
      in vivo. METHODS: Cells were treated with Tan-IIA and growth inhibition was
      assessed. Cell cycle profiles after Tan-IIA treatment were determined by flow
      cytometry. Expression levels of cell cycle regulatory proteins and apoptosis
      related proteins were determined after Tan-IIA treatment. Expression levels of
      endoplasmic reticulum (ER) stress-regulated genes were determined to investigate
      their role in Tan-IIA-induced cell death. GADD153 expression was knocked down by
      small interfering RNA (siRNA) transfection. Rate of cell death and proliferation
      was obtained by 3-(4,5-dimethyl thizol-2-yl)-2,5-diphenyl tetrazolium bromide
      assay. Antitumor activity of Tan-IIA was performed in LNCaP xenograft model.
      RESULTS: Our results showed that Tan-IIA caused prostate cancer cell death in a
      dose-dependent manner, and cell cycle arrest at G0/G1 phase was noted, in LNCaP
      cells. The G0/G1 phase arrest correlated with increase levels of CDK inhibitors
      (p16, p21 and p27) and decrease of the checkpoint proteins. Tan-IIA also induced
      ER stress in prostate cancer cells: activation and nuclear translocation of
      GADD153/CCAAT/enhancer-binding protein-homologous protein (CHOP) were identified,
      and increased expression of the downstream molecules GRP78/BiP, inositol
      requiring protein-1alpha and GADD153/CHOP were evidenced. Blockage of
      GADD153/CHOP expression by siRNA reduced Tan-IIA-induced cell death in LNCaP
      cells. Tan-IIA also suppressed LNCaP xenograft tumor growth, causing 86.4%
      reduction in tumor volume after 13 days of treatment. CONCLUSIONS: Our findings
      suggest that Tan-IIA causes G0/G1 cell cycle arrest in LNCaP cells and its
      cytotoxicity is mediated at least partly by ER stress induction. These data
      provide evidence supporting Tan-IIA as a potential anticancer agent by inducing
      ER stress in prostate cancer.

PMID- 24042855
TI  - Only slow decline in exercise capacity in the natural history of patients with
      congenital heart disease: a longitudinal study in 522 patients.
AB  - OBJECTIVE: Exercise studies in patients with congenital heart disease (CHD)
      suggest that exercise capacity declines progressively. This study aims to assess
      the natural history of exercise capacity in patients with CHD from serial
      cardiopulmonary exercise tests (CPETs) and to identify factors that are
      associated with the rate of decrease. PATIENTS AND METHODS: From July 2001-August
      2012 we included all patients with CHD who had two CPETs separated by at least
      six months. Patients with any kind of intervention (surgery, catheter
      intervention, or change in medication) between the two tests were excluded.
      RESULTS: In 522 patients (24.8 +/- 10.2 years, 215 female) peak oxygen uptake
      (VO2) was reduced to 80.0 +/- 20.7% predicted and declined significantly during a
      mean follow-up of 2.5 +/- 1.8 years to 78.1 +/- 20.4% predicted (p < 0.0001). The
      annual declining rate of peak VO2 was only -1.01 +/- 6.83% points per year.
      Higher peak oxygen pulse (% predicted) (r = -0.230; p < 0.0001), higher peak VO2
      (% predicted) (r = -0.213; p < 0.0001) at baseline testing and the presence of a
      pacemaker (r = -0.095; p = 0.031) were only weakly associated with a more rapid
      decline in peak VO2 (% predicted) over time. The decline was independent from
      diagnosis, heart defect severity, systemic ventricular morphology and age.
      CONCLUSIONS: There was a progressive, but slow, decline in the natural history of
      exercise capacity in all kind of patients with CHD. Except for having a
      pacemaker, we could not find any factors associated with this decline.

PMID- 24042856
TI  - NSAID-antihypertensive drug interactions: which outpatients are at risk for a
      rise in systolic blood pressure?
AB  - BACKGROUND: Management guidelines for drug-drug interactions between non
      steroidal anti-inflammatory drugs (NSAIDs) and antihypertensives recommend blood
      pressure monitoring in hypertensive patients. We measured the short-term effect
      of initiating NSAIDs on systolic blood pressure (SBP) in users of
      antihypertensives, aiming to investigate which outpatients are at risk for an
      increase in SBP in daily clinical practice. DESIGN: A cohort study with a nested
      case-control design in Dutch community pharmacies. METHODS: Patients with a drug
      drug interaction alert for a newly initiated NSAID and antihypertensive were
      interviewed and their SBP was measured at T0, after one week (T1) and after two
      weeks (T2). We evaluated risk factors for exceeding a predefined limit of change
      (PLoC) in SBP (>= 10 mmHg to >= 140 mmHg) at T1 and T2 versus T0. RESULTS: For
      112 patients the SBP at T0 was measured. Two patients were excluded (T0 SBP >=
      180 mmHg). PLoC was exceeded in 10 patients (10.4%) at T1 and in seven patients
      (8.0%) at T2. Patients using etoricoxib (odds ratio (OR), 21.0; 95% confidence
      interval (CI), 3.7-120.6) and patients using >1 defined daily dose of an NSAID
      (OR, 3.3; 95% CI, 1.1-10.0) were at increased risk of a rise in SBP. CONCLUSIONS:
      A newly initiated NSAID has an immediate clinically relevant effect on SBP in
      some users of antihypertensives. Management guidelines for NSAID-antihypertensive
      drug-drug interactions should advise SBP monitoring before and after initiation
      of an NSAID or intensification of NSAID therapy. Monitoring is especially
      relevant in patients prescribed high dosages of NSAIDs. Etoricoxib should not be
      used in hypertensive patients.

PMID- 24042858
TI  - A New Technology in Cartilage Tissue Engineering: Scaffold - Free Cartilage
      Transplantats (Sfct).

PMID- 24042857
TI  - Human group V secretory phospholipase A2 is associated with lipid rafts and
      internalized in a flotillin-dependent pathway.
AB  - The mechanisms of secretory phospholipase A2 (sPLA2) action are not understood
      clearly. Previously, it was suggested that sPLA2s are internalized into cells for
      the targeting of sPLA2 to intracellular action sites. However, the mechanisms for
      sPLA2 internalization remain to be identified. The present study demonstrated for
      the first time that human group V sPLA2 (hVPLA2) is associated with lipid rafts
      and is internalized in a flotillin-dependent pathway. The lipid raft association
      was probed by cholesterol-sensitive enrichment of hVPLA2 in low-density fractions
      and co-patching of ganglioside GM1 rafts through cross-linking of hVPLA2 in
      HEK293 and CHO cells. The hVPLA2 associated with lipid rafts was shown to be
      internalized into HEK293 cells at a relatively rapid rate (t1/2 =16 min) and this
      internalization was inhibited by the knockdown of flotillin-1, but not by
      chlorpromazine, an inhibitor of clathrin-mediated endocytosis. Moreover,
      internalized hVPLA2 was shown to be colocalized extensively with flotillin-1 in a
      punctate structure, but not caveolin-1. These data revealed that the
      internalization of hVPLA2 is mediated by flotillin-1. Attenuation of arachidonic
      acid release from plasma membrane through the association of hVPLA2 with lipid
      rafts suggested that this association with lipid rafts may be important in
      protecting mammalian cells from excessive degradation of plasma membrane and
      trafficking hVPLA2 into intracellular targets.

PMID- 24042859
TI  - Changes in Shape and Density of Denervated Muscles: Case Reports.

PMID- 24042860
TI  - Electrospinning Auricular Shaped Scaffolds for Tissue Engineering.

PMID- 24042861
TI  - Antioxidantien als Strategie zur Optimierung der Kryokonservierung von
      Stammzellen fur das Tissue Engineering.

PMID- 24042862
TI  - Thermomanagement for Neonates Methods of Keeping Neonates Warm.

PMID- 24042863
TI  - Physiology and Pathophysiology of Thermoregulation in the Neonate.

PMID- 24042864
TI  - Measurement of Body Temperature in Infants.

PMID- 24042865
TI  - Semi-Invasive Cardiac Output Measurement Based on Pulse Contour: A Review.

PMID- 24042866
TI  - Thermomanagement in Neonatology and Paediatrics: Clinical Problems and
      Challenges.

PMID- 24042867
TI  - Monitoring the Activation of the Sympathetic Nervous System to Improve
      Hemodialysis Processes.

PMID- 24042868
TI  - Ongoing Development and First Long-Term Trials of a Cardiac Output Monitoring
      System in the Pulmonary Artery (Compass).

PMID- 24042869
TI  - Hemodynamic Surrogate Measures Symplifying Neurally Mediated Syncope Management.

PMID- 24042871
TI  - An Electromagnetic Simulation Environment, to Construct Microwave Imaging
      Algorithms.

PMID- 24042870
TI  - An Interdisciplinary Workshop to Identify Alcohol Craving Based on
      Psychophysiological Sensor Data.

PMID- 24042872
TI  - Model-based Optimization of Ventilator Settings for Bedside Application.

PMID- 24042873
TI  - Continuous Blood Glucose Monitoring (Cgm) System Based on Intravenous
      Microdialysis and Glucose Sensing.

PMID- 24042874
TI  - Spectral and Temporal Modulation of Pulsoxymetry Probe Light Signals - Improved
      Recombination of Specrtally Decomposed Light.

PMID- 24042875
TI  - Quality index control system for shape identification of intratidal compliance
      volume curve with fuzzy logic.

PMID- 24042876
TI  - A Case of Mild Hypertension what can we Learn from over 900 Days of Data Records?

PMID- 24042877
TI  - Exclusion of Adverse Hemodynamic Programming in Cardiac Resynchronization
      Therapy.

PMID- 24042878
TI  - Thermo-Management in Neonatal Care: Future Needs.

PMID- 24042879
TI  - An Intravesical Measurement System for Catheterless Long-Term Urodynamics.

PMID- 24042880
TI  - A Modular System for Capacitive Ecg-Acquisition.

PMID- 24042881
TI  - Noise in respiratory signals influences dynamic respiratory system compliance
      analysis: A simulation study.

PMID- 24042882
TI  - User-Centred Evaluation of Lower-Limb Orthoses: A new Approach.

PMID- 24042883
TI  - Software-Based Risk Management Documentation for Medical Devices.

PMID- 24042884
TI  - System-Triggered Error Induction for Usability Research and Training: The
      Steinfurt Method.

PMID- 24042885
TI  - Future Challenges for Medical Device Manufacturers Regarding the Revision of the
      European Legislation.

PMID- 24042886
TI  - Systematic Consideration of Haptic Perception in the Design of Task-Specific
      Haptic Systems.

PMID- 24042887
TI  - "Design for Six Sigma" fur Medizinprodukte.

PMID- 24042888
TI  - Problems of Use in the View of Increasing Automation in Operating Theatres for
      ENT Fess Surgery.

PMID- 24042890
TI  - Standardised Documentation of Instrument use during Laparoscopic Surgery.

PMID- 24042889
TI  - Ergonomics of Selected Laparoscopic Procedures - Need for Action?

PMID- 24042891
TI  - Development of a simulation and training system for head and neck tumour
      diagnosis.

PMID- 24042892
TI  - Umsatzpotentiale fur Assistenzsysteme und Dienstleistungen fur ein
      Selbstbestimmtes Leben.

PMID- 24042893
TI  - Determination of Gait Parameters from the Wearable Motion Analysis System eSHOE.

PMID- 24042894
TI  - Monitoring Recovery after Elbow Surgery Using Smartphone.

PMID- 24042895
TI  - Mobile Patient Monitoring - Regulatory Considerations.

PMID- 24042896
TI  - Assistenzsysteme und Dienstleistungen fur ein selbstbestimmtes Leben.

PMID- 24042897
TI  - Usability requirements for mobile documentation from physicians and nurses.

PMID- 24042898
TI  - The European Next Generation Ambient Assistend Living Innovation Alliance -
      AALIANCE2.

PMID- 24042899
TI  - Improving Emergency Care by Highly Specialised Applications.

PMID- 24042900
TI  - User Centred Gathering of Requirements for Mobile Assistance Services for People
      with Mild to Moderate Dementia.

PMID- 24042901
TI  - A Patient Centered Sensor System for Decubitus Risk Predection and Prevention.

PMID- 24042902
TI  - A Social Assistive Robot in an Intelligent Environment.

PMID- 24042903
TI  - Script: Usability of Hand & Wrist Tele-Rehabilitation for Stroke Patients
      Involving Personal Tele-Robotics.

PMID- 24042904
TI  - Validation of Different Parameters Extracted from 3D Images for Leg Oedema
      Detection.

PMID- 24042905
TI  - A Laboratory for AAL Applications.

PMID- 24042906
TI  - Mhealth Supporting Dynamic Medication Management during Home Monitoring of Heart
      Failure Patients.

PMID- 24042907
TI  - Comparison and Evaluation of Classical and Modern Beamforming.

PMID- 24042908
TI  - The depiction of labeled guidewires in a phantom in an interventional MRI
      setting.

PMID- 24042909
TI  - Impact of Filtering on Region of Interest Estimation from Diffusion Weighted
      Brain Images.

PMID- 24042910
TI  - Simulation-Based Evaluation of Edged Ultrasound Transducer Shapes for
      Optoacoustic Tomography in Biomedical Imaging.

PMID- 24042911
TI  - Comparison of Different Algorithms for Robust Detection of Pupils in Real-Time
      Eye-Tracking Experiments.

PMID- 24042912
TI  - High Homogeneous Saddle Drive Field Coil for Magnetic Particle Spectroscopy.

PMID- 24042913
TI  - Recording the Movement Behaviour of a Bolus in the Rumen of Cattle with a
      Magnetic Detector System.

PMID- 24042914
TI  - Computer aided Planning and Navigation for Patient-Specific Deep Brain
      Stimulation.

PMID- 24042915
TI  - Non-Scanning Magnetic Field Imaging with Laser-Pumped Atomic Magnetometer.

PMID- 24042916
TI  - Cell Simulation for Validation of Cell Micrograph Evaluation Algorithms.

PMID- 24042917
TI  - Volume and Surface Estimation of Vital Alveolar Macrophages in Vitro by 2D
      Microscopy Imaging.

PMID- 24042918
TI  - Evaluation of an Mr Compatible Doppler-Ultrasound Device as a New Trigger Method
      in Cardiac Mri: A Quantitative Comparison to ECG.

PMID- 24042919
TI  - Spatial Reconstruction of Human Thyroid based on Ultrasound and CT Image Data
      Fusion.

PMID- 24042920
TI  - Lymphatic Tissue and Superparamagnetic Nanoparticles - Magnetic Particle Imaging
      for Detection and Distribution in a Breast Cancer Model.

PMID- 24042921
TI  - Comparison of Open Scanner Designs for Interventional Magnetic Particle Imaging.

PMID- 24042922
TI  - Evaluation of a New Measurement System Combining Body Plethysmography and
      Electrical Impedance Tomography.

PMID- 24042923
TI  - Depth Dependancy of Fourier Spectra of Catheters in Turkey Breast.

PMID- 24042924
TI  - Effect of Noise on a Nonlinear Compressibility Reconstruction Approach under
      Various Excitation Modi.

PMID- 24042925
TI  - Development & Evaluation of a Surgical Stereo Vision Laser-Scanning Surface
      Recognition System.

PMID- 24042926
TI  - Contrast enhancement methods in Optical Coherence Tomography using spectral
      features.

PMID- 24042927
TI  - Combined Modality for Ultrasound Imaging and Electromagnetic Tracking.

PMID- 24042928
TI  - 3D Optical Coherence Tomography for Investigating Alveolar Structures During
      Total Liquid Ventilation.

PMID- 24042929
TI  - Scanner Construction for a Dynamic Field Free Line in Magnetic Particle Imaging.

PMID- 24042930
TI  - Marker Removal for C-arm Pose Estimation based Bronchoscope Navigation using
      Image Inpainting.

PMID- 24042931
TI  - Wideband Probe for Magnetic Quadrupole Resonance Spectroscopy.

PMID- 24042932
TI  - A Novel Concept of Integrated Process Chain for Surgical Splint Generation Based
      on Clinical Assessment in Orthognathic Surgery.

PMID- 24042933
TI  - Visualization Aspects of Motion Tracking and Analysis of the Outer Surface of the
      Left Ventricle.

PMID- 24042934
TI  - Software-Based Imaging and Segmentation of Corneal Nerve Fibres.

PMID- 24042935
TI  - Correlation of Macroscopic and Histopathologic Findings with MRI in Forensic
      Examinations.

PMID- 24042936
TI  - Quantitative Estimation of Left Ventricular Myocardial Perfusion Based on Dynamic
      CT Scans.

PMID- 24042937
TI  - A Hybird Optimization Approach for 2D-3D Registrationbased Fusion of Ultrasound
      and X-Ray.

PMID- 24042938
TI  - An approach to validate ultrasound surface segmentation of the heart.

PMID- 24042939
TI  - Quantitative reconstruction of a magnetic nanoparticle distribution using a non
      negativity constraint.

PMID- 24042940
TI  - Analysis of Patterns in Tremor Diagnosis Spiral Drawings for Automated
      Classification.

PMID- 24042941
TI  - GPU-Based Interactive Segmentation For Planning And Performing Neurosurgical
      Interventions.

PMID- 24042942
TI  - Developing staining protocols for visualization of tissue-engineering scaffolds
      using micro computed tomography in native wet state.

PMID- 24042943
TI  - Simple Test Of Transducer Arrays By Imaging Of Ultrasound Emission Into Air.

PMID- 24042944
TI  - Temperature Dependency of T1 Relaxation Time in Unfixed and Fixed Human Brain
      Tissue.

PMID- 24042945
TI  - Simulation Study of a Single-Sided Magnetic Particle Imaging Device.

PMID- 24042946
TI  - An Active Transmit/Receive NMR Magnetometer for Field Monitoring in Ultra High
      Field MRI Scanners.

PMID- 24042947
TI  - Precision of an MPI Scanner Construction: Registration of Measured and Simulated
      Magnetic Fields.

PMID- 24042948
TI  - Perfusion Model Approximation in Cerebral Tumours: Feature Images and Computation
      Times.

PMID- 24042949
TI  - Automated Detection of Rigid Particles in Phase-Contrast Micrographs of Urine
      Sediments.

PMID- 24042950
TI  - Investigation of alveolar stability in the rat lung using transthoracic
      endoscopy.

PMID- 24042951
TI  - Automatic gesture recognition based on thermography.

PMID- 24042952
TI  - Mobile Smarttracking - Finding Objective Parameters for Determining Fitness to
      Drive.

PMID- 24042953
TI  - A Confocal Microscopy Study of the Anterior Corneal Mosaic in the Sub-Basal Nerve
      Plexus.

PMID- 24042954
TI  - Regulatory Genomics - Decoding Drosophila Regulatory Sequences.

PMID- 24042955
TI  - Systems Biology Analysis of Kinase Inhibitor Action in Leukemia Treatments.

PMID- 24042956
TI  - Model-based Decision Support: Requirements and Future for its Application in
      Surgery.

PMID- 24042957
TI  - High-Troughput Characterization and Comparison of Microbial Communities.

PMID- 24042960
TI  - A rare case of iatrogenic pseudoaneurysm of the left brachiocephalic vein after
      central venous catheterization treated with thrombin injection.
AB  - Rupture of the central veins with venous pseudoaneurysm formation is an unusual
      complication of central venous catheterization. Only seven cases of
      brachiocephalic venous pseudoaneurysm have been reported in the literature (among
      these only one was secondary to central venous catheterization). Plain
      radiographic examination of the chest may show widening of the mediastinum,
      pleural effusion (haemothorax), and/or opacity overlying the hemithorax of the
      injured vein. Further evaluation using either computed tomography or magnetic
      resonance imaging can be performed. Venography is considered an important tool,
      especially when an intervention is planned. We present the first reported case of
      brachiocephalic vein pseudoaneurysm treated solely with thrombin injection. The
      imaging, other treatment options, and literature review of brachiocephalic venous
      pseudoaneurysm are also discussed. 

PMID- 24042961
TI  - Endovascular treatment for the basilar artery dissection.
AB  - PURPOSE: To determine the safety and efficacy of endovascular therapy for the
      treatment of basilar artery dissection (BAD). METHODS: Patients with BAD admitted
      to our hospital from June 2002 to December 2011 were retrospectively reviewed.
      Strict inclusion and exclusion criteria were made. At enrollment, patients'
      manifestations were evaluated. The different devices and techniques used for each
      patient were recorded and further classified into two groups: the coiling-only
      group, in which lesions were treated only with coils; and the stented group, in
      which lesions were treated with only stents or by stent-assisted embolization.
      Shapes of BAD were described and classified into three types: dilation, pearl-and
      string sign, and stenosis. Presentations of BAD were classified as ruptured or
      unruptured. Digital subtraction angiography results obtained immediately after
      intervention and at follow-up were evaluated and classified into two groups:
      stable/improved or recanalized/worsened. Clinical outcome was evaluated by
      modified Rankin Scale score. RESULTS: A total of 29 patients were included, and
      28 of them were followed up clinically and angiographically. No significant
      difference of recurrence rate existed between ruptured and unruptured BAD. The
      coiling-only group demonstrated a significantly higher recurrence rate than the
      stent-assisted group. In the 22 instances of BAD presenting with dilated shapes,
      stented cases had better radiological outcome than unstented cases, and initial
      packing of completely/near completely occluded cases had better radiological
      follow-up results. CONCLUSION: Endovascular therapy proved safe and effective.
      Stent placement and initial complete occlusion were favorable factors for follow
      up stable/improved outcome.

PMID- 24042962
TI  - A new model for nurse practitioner utilization in primary care: increased
      efficiency and implications.
AB  - BACKGROUND: Nurse practitioners (NPs) play an important role in providing quality
      primary care. However, little is known about organizational processes that best
      utilize NPs in care delivery and what kind of resources and support NPs need to
      deliver quality care within their organizations. In primary care settings, NPs
      often receive little support from ancillary personnel compared with physicians.
      PURPOSE: The aim of this article was to compare the productivity and cost
      efficiency of NP utilization models implemented in primary care sites with and
      without medical assistant (MA) support. METHODOLOGY/APPROACH: We develop queueing
      models for these NP utilization models, of which the parameters are extracted
      from literature or government reports. Appropriate analyses are conducted to
      generate formulas and values for the productivity and cost efficiency.
      Sensitivity analyses are conducted to investigate different scenarios and to
      verify the robustness of findings. FINDINGS: The productivity and cost efficiency
      of these models improve significantly if NPs have access to MA support in serving
      patients. On the basis of the model parameters we use, the average cost of
      serving a patient can be reduced by 9%-12% if MAs are hired to support NPs. Such
      improvements are robust across practice environments with different variability
      in provider service times. Improving provider service rate is a much more
      effective strategy to increase productivity compared with reducing the
      variability in provider service times. PRACTICE IMPLICATIONS: To contain costs
      and improve the utilization of NPs in primary care settings, MA assistance for
      NPs is necessary.

PMID- 24042963
TI  - Understanding claims-based quality profiles in primary care practice: the role of
      office system tools and health information technology.
AB  - BACKGROUND: Claims-based quality profiles are increasingly used by third-party
      payers as a means of monitoring and remunerating physician performance. As
      traditional approaches to assessing performance yield to electronically generated
      data, identifying practice tools capable of influencing the behavior of these
      measures becomes essential to effectively managing medical practices. PURPOSE:
      The aim of this study was to examine the effect of using office system tools
      (i.e., patient registries, physician reminders, and flow sheets) and health
      information technology (HIT) on claims-based quality profile scores in primary
      care practices. METHODOLOGY: We analyzed survey responses from primary care
      physicians (n = 191) regarding their use of office system tools and HIT. These
      responses were linked to quality profile scores obtained from a Blue Cross Blue
      Shield of Texas claims-based data set. FINDINGS: Elevated quality profile scores
      were associated with physicians who reported higher use of HIT. In addition, the
      influence of one office system tool, physician reminders, was contingent upon the
      availability and use of HIT. PRACTICE IMPLICATIONS: Our findings indicate that
      primary care practices that fail to implement or use HIT appropriately will fare
      poorly in systems that monitor and reward performance based on measures derived
      from claims data. Linking prompts or reminders directly to clinical actions that
      influence quality indicators endorsed by payers should be a component of quality
      assurance programs.

PMID- 24042964
TI  - Methicillin-resistant Staphylococcus aureus: where is it coming from and where is
      it going?

PMID- 24042965
TI  - Patient-specific instrumentation for total knee arthroplasty does not match the
      pre-operative plan as assessed by intra-operative computer-assisted navigation.
AB  - PURPOSE: The introduction of patient-specific instruments (PSI) for guiding bone
      cuts could increase the incidence of malalignment in primary total knee
      arthroplasty. The purpose of this study was to assess the agreement between one
      type of patient-specific instrumentation (Zimmer PSI) and the pre-operative plan
      with respect to bone cuts and component alignment during TKR using imageless
      computer navigation. METHODS: A consecutive series of 30 femoral and tibial
      guides were assessed in-theatre by the same surgeon using computer navigation.
      Following surgical exposure, the PSI cutting guides were placed on the joint
      surface and alignment assessed using the navigation tracker. The difference
      between in-theatre data and the pre-operative plan was recorded and analysed.
      RESULTS: The error between in-theatre measurements and pre-operative plan for the
      femoral and tibial components exceeded 3 degrees  for 3 and 17% of the sample,
      respectively, while the error for total coronal alignment exceeded 3 degrees  for
      27% of the sample. CONCLUSION: The present results indicate that alignment with
      Zimmer PSI cutting blocks, assessed by imageless navigation, does not match the
      pre-operative plan in a proportion of cases. To prevent unnecessary increases in
      the incidence of malalignment in primary TKR, it is recommended that these
      devices should not be used without objective verification of alignment, either in
      real-time or with post-operative imaging. Further work is required to identify
      the source of discrepancies and validate these devices prior to routine use.
      LEVEL OF EVIDENCE: II.

PMID- 24042966
TI  - Maqdes A, Levy B, Klouche S, Hardy P: The feasibility and results of an
      arthroscopic removal of humeral locking plates and glenohumeral arthrolysis after
      proximal humeral fractures. Knee surg sports traumatol arthrosc 2013 Feb 9. [Epub
      ahead of print] Doi 10.1007/s00167-013-2437-8.

PMID- 24042967
TI  - Flash chemistry: flow chemistry that cannot be done in batch.
AB  - Flash chemistry based on high-resolution reaction time control using flow
      microreactors enables chemical reactions that cannot be done in batch and serves
      as a powerful tool for laboratory synthesis of organic compounds and for
      production in chemical and pharmaceutical industries. 

PMID- 24042968
TI  - Genome-wide mapping of gene-microbiota interactions in susceptibility to
      autoimmune skin blistering.
AB  - Susceptibility to chronic inflammatory diseases is determined by immunogenetic
      and environmental risk factors. Resident microbial communities often differ
      between healthy and diseased states, but whether these differences are of primary
      aetiological importance or secondary to the altered inflammatory environment
      remains largely unknown. Here we provide evidence for host gene-microbiota
      interactions contributing to disease risk in a mouse model of epidermolysis
      bullosa acquisita, an autoantibody-induced inflammatory skin disease. Using an
      advanced intercross, we identify genetic loci contributing to skin microbiota
      variability, susceptibility to skin blistering and their overlap. Furthermore, by
      treating bacterial species abundances as covariates with disease we reveal a
      novel disease locus. The majority of the identified covariate taxa are
      characterized by reduced abundance being associated with increased disease risk,
      providing evidence of a primary role in protection from disease. Further
      characterization of these putative probiotic species or species assemblages
      offers promising potential for preventative and therapeutic treatment
      development. 

PMID- 24042969
TI  - Structural and functional changes of the coronary arteries in elderly senile
      patients with essential hypertension.
AB  - The aim of this study was to evaluate the effect of aging on the changes to the
      structure and function of coronary arteries in senile elderly patients with
      essential hypertension. Patients (aged 60-80 years) were divided into three
      groups. The 195 hypertensive patients were divided into four sub-groups according
      to the duration of hypertension. The changes to the coronary arteries (left and
      right) of all those patients were tested using the following index by 64 coronary
      computed tomography (CT) scans. The 24 h systolic blood pressure (SBP) and other
      blood biochemical parameters were assayed for all patients. We found that the
      value of the body mass index (BMI), total cholesterol (TC) and low density
      lipoproteins (LDL) were lower, but age and high density lipoproteins (HDL) were
      higher in the group of very elderly patients with hypertension (Group I; P<0.05)
      compared with those of a group of elderly patients with hypertension (Group III).
      The left anterior descending branch calcification score (CSLAD), total
      calcification score (CST), pulse pressure (PP), the left main branch
      calcification score (CSLM), the left circumflex branch calcification score
      (CSLCX) were significantly increased in Group I compared with Group III (P<0.01
      and P<0.05, respectively). In addition, the 24 h SBP value for Group I was higher
      than in the 'very elderly without hypertension' group (Group II). Hence, in
      elderly patients, a decrease in the levels of BMI, HDL, TC and LDL accompanies
      aging. Furthermore, the decline of arterial compliance and increase in arterial
      stiffness develops with age. Aging is more likely to lead to atherosclerosis in
      the coronary arteries, particularly in the left main coronary artery and its main
      branches. Aging is an uncontrollable risk factor, which plays a crucial role in
      coronary artery atherosclerosis.

PMID- 24042970
TI  - Parental educational level and injury incidence and mortality among foreign-born
      children: a cohort study with 46 years follow-up.
AB  - BACKGROUND: Injury risk during childhood and adolescence vary depending on socio
      economic factors. The aim of this study was to study if the risk of fatal and non
      fatal unintentional injuries among foreign-born children was similar across
      parental educational level or not. METHODS: In this retrospective cohort study we
      followed 907,335 children between 1961 and 2007 in Sweden. We established the
      cohort by linkage between Swedish national registers including cause of death
      register and in-patient register, through unique Personal Identification Numbers.
      The main exposure variable was parental (maternal and paternal) educational
      level. The cohorts was followed from start date of follow-up period, or date of
      birth whichever occurred last, until exit date from the cohort, which was date of
      hospitalization or death due to unintentional injury, first emigration, death due
      to other causes than injury or end of follow-up, whichever came first. We
      calculated hazard ratios (HR) with 95% confidence intervals (95% CI) by Cox
      proportional hazards regression models. RESULTS: Overall, we found 705 and 78,182
      cases of death and hospitalization due to unintentional injuries, respectively.
      Risk of death and hospitalization due to unintentional injuries was statistically
      significantly 1.48 (95% CI: 1.24-1.78) and 1.10 (95% CI: 1.08-1.12) times higher
      among children with lowest parental educational level (9 years and shorter years
      of study) compared to children with highest parental educational level (+13 years
      of study). We found similar results when stratified our study group by sex of
      children, by maternal and paternal educational level separately, and injury type
      (traffic-related, fall, poisoning, burn and drowning). CONCLUSIONS: It seems
      injury prevention work against unintentional injuries is less effective among
      children with low parental education compared with those with higher parental
      education. We recommend designing specific preventive interventions aiming at
      children with low parental education.

PMID- 24042971
TI  - Prevalence of tobacco use among adults in Egypt, 2009.
AB  - INTRODUCTION: We assessed the differences in overall use of tobacco and in the
      use of various tobacco products, by sex and by frequency of use across various
      demographic groups. METHODS: We used data from the Global Adult Tobacco Survey
      (GATS), conducted in 2009 in Egypt. The data consist of answers to GATS by 20,924
      respondents from a nationally representative, multistage probability sample of
      adults aged 15 years or older from all regions of Egypt. Current tobacco use was
      defined as current smoking or use of smokeless tobacco products, either daily or
      occasionally. We analyzed the differences in current cigarette, shisha, and
      smokeless tobacco use by sex and frequency of use (daily or occasional); and by
      demographic characteristics that included age, region, education level and
      employment status. RESULTS: Overall, 19.7% of the Egyptian population currently
      use some form of tobacco. Men (38.1% [95% confidence interval (CI) 36.8-39.4])
      are much more likely than women (0.6% [95% CI 0.4-0.9]) to use tobacco. Almost
      96% of men who use tobacco, do so daily. Men are more likely to use manufactured
      cigarettes (31.8% [95% CI 30.6-33.1]) than shisha (6.2% [95% CI 5.6-6.9]) or
      smokeless tobacco (4.1% [95% CI 3.4-4.8]). Few women use tobacco (cigarettes
      (0.2%), shisha (0.3%) and smokeless tobacco (0.3%)); however, all women who
      currently smoke shisha, do so daily. Lower educational status, being between ages
      25-64 and being employed predicted a higher use of tobacco. CONCLUSION: Egypt has
      implemented several initiatives to reduce tobacco use. The World Health
      Organization (WHO) MPOWER technical package, which aims to reverse the tobacco
      epidemic, is implemented at various levels throughout the country. Our findings
      show that there is significant variation in the prevalence of tobacco use and
      types of tobacco used by adult men and women in Egypt. GATS data can be used to
      better understand comparative patterns of tobacco use by adults, which in turn
      can be used to develop interventions.

PMID- 24042972
TI  - Exposure to anti- and pro-tobacco advertising, promotions or sponsorships:
      Turkey, 2008.
AB  - INTRODUCTION: In 2008, Turkey became one of 26 countries with a complete ban on
      all forms of direct and indirect tobacco marketing. We assessed the level of
      exposure to anti- and pro-cigarette advertising and to cigarette promotions and
      sponsorships among various demographic groups in Turkey. METHODS: We used the
      data from the Global Adult Tobacco Survey (GATS), conducted in November 2008 in
      Turkey. The data consist of answers to GATS questions by 9030 respondents from a
      nationally representative, multistage probability sample of adults 15 years of
      age or older. To find differences in exposure to the advertising by sex, age,
      education level and smoking status, we analyzed responses to GATS questions about
      cigarette advertisements and anti-cigarette smoking information in various forms
      and through various advertising channels, during the 30 days before the survey,
      using bivariate analysis. RESULTS: Overall, 13.3% of respondents aged 15 years or
      older noticed some type of cigarette marketing during the 30 days before the
      survey: 7.1% saw advertisements, 5.3% saw promotions and 3.3% saw sports
      sponsorships. Men were more likely than women to have seen cigarette promotions
      (7.8% versus 3.0%) and sports sponsorships (5.3% versus 1.4%). Respondents aged
      15-24 years were more likely than those aged 25 years or older to have seen
      cigarette advertisements (10.2% versus 6.2%), promotions (8.7% versus 4.4%) and
      sponsorships (6.6% versus 2.3%), respectively. Respondents were most likely to
      have seen cigarette advertisements on television (3.4%) or in shops (2.7%). In
      addition, 2.8% of respondents reported seeing a clothing item with a brand name
      or logo, 2.5% reported that they received free samples of cigarettes and 0.3%
      received gifts along with the purchase of cigarettes. Almost 9 of 10 survey
      respondents (88.8%) reported having noticed some anti-cigarette information
      during the 30 days before the survey. Most anti-cigarette information was seen on
      television (85.5%). The anti-cigarette information was seen by slightly more
      cigarette smokers (91.6%) than nonsmokers (87.6%). Persons with less than a
      primary education were less likely to notice anti-cigarette information than
      those with a higher level of education, in all examined media channels.
      CONCLUSIONS: Our findings showed a low prevalence of noticing cigarette
      marketing, which indicates high compliance with the Turkish law banning such
      marketing. GATS data provide an in-depth understanding of the level of exposure
      to pro- and anti-cigarette information in 2008 and they are of practical
      assistance to those who implement policies to reduce the demand for tobacco. The
      challenge now is to maintain rigorous enforcement. To do so requires ongoing
      surveillance to produce data on the effectiveness of the enforcement efforts.

PMID- 24042973
TI  - Tracking MPOWER in 14 countries: results from the Global Adult Tobacco Survey,
      2008-2010.
AB  - BACKGROUND: The World Health Organization (WHO) MPOWER is a technical package of
      six tobacco control measures that assist countries in meeting their obligations
      of the WHO Framework Convention Tobacco Control and are proven to reduce tobacco
      use. The Global Adult Tobacco Survey (GATS) systematically monitors adult tobacco
      use and tracks key tobacco control indicators. METHODS: GATS is a nationally
      representative household survey of adults aged 15 and older, using a standard and
      consistent protocol across countries; it includes information on the six WHO
      MPOWER measures. GATS Phase I was conducted from 2008-2010 in 14 high-burden low-
      and middle-income countries. We selected one key indicator from each of the six
      MPOWER measures and compared results across 14 countries. RESULTS: Current
      tobacco use prevalence rates ranged from 16.1% in Mexico to 43.3% in Bangladesh.
      We found that the highest rate of exposure to secondhand smoke in the workplace
      was in China (63.3%). We found the highest 'smoking quit attempt' rates in the
      past 12 months among cigarette smokers in Viet Nam (55.3%) and the lowest rate
      was in the Russian Federation (32.1%). In five of the 14 countries, more than one
      half of current smokers in those 5 countries said they thought of quitting
      because of health warning labels on cigarette packages. The Philippines (74.3%)
      and the Russian Federation (68.0%) had the highest percentages of respondents
      noticing any cigarette advertising, promotion and sponsorship. Manufactured
      cigarette affordability ranged from 0.6% in Russia to 8.0% in India. CONCLUSIONS:
      Monitoring tobacco use and tobacco control policy achievements is crucial to
      managing and implementing measures to reverse the epidemic. GATS provides
      internationally-comparable data that systematically monitors and tracks the
      progress of the other five MPOWER measures.

PMID- 24042974
TI  - Exposure to secondhand smoke among adults - Philippines, 2009.
AB  - INTRODUCTION: We assessed the differences in exposure to secondhand smoke (SHS)
      among adults at home, in indoor workplaces, and in various public places in the
      Philippines across various socio-demographic groups. METHODS: Data from the
      Global Adult Tobacco Survey conducted in 2009 in the Philippines were used. The
      data consist of survey answers from 9705 respondents from a nationally
      representative, multistage probability sample of adults aged 15 years or older.
      We considered that respondents were exposed to SHS if during the previous 30 days
      they reported that they lived in a home, worked in a building, or visited a
      public place where people smoked. The public places included in our analysis were
      indoor workplaces, public transportation vehicles, restaurants, government
      buildings or offices, and healthcare facilities. The differences in various
      socioeconomic and demographic groups' exposure to SHS in these places were also
      examined. RESULTS: Of respondents who reported working indoors, 36.8% were
      exposed to SHS. Men (43.3% [95% CI 39.7-46.9]) were more likely than women (28.8%
      [95% CI 25.4-32.4]) to be exposed to SHS (p < 0.001). Of those working in sites
      where smoking was not allowed, 13.9% were exposed to SHS, whereas 66.5% were
      exposed where smoking is allowed in some enclosed areas, and 90.7% were exposed
      where smoking is allowed everywhere. During the 30 days preceding the survey,
      more than 50% of those who took public transportation were exposed to SHS;
      exposure for those who visited public buildings was 33.6% in restaurants, 25.5%
      in government buildings or offices, and 7.6% in healthcare facilities.
      CONCLUSION: Despite a national law passed and several local government ordinances
      that have promulgated smoke-free workplaces, schools, government offices, and
      healthcare facilities, our findings show that a large proportion of adults were
      exposed to SHS at work and in public places, which offers opportunities to
      strengthen and improve enforcement of the smoke-free initiatives and ordinances
      in the Philippines.

PMID- 24042975
TI  - Methodology of the Global Adult Tobacco Survey - 2008-2010.
AB  - In 2008, the Centers for Disease Control and Prevention (CDC) and the World
      Health Organization developed the Global Adult Tobacco Survey (GATS), an
      instrument to monitor global tobacco use and measure indicators of tobacco
      control. GATS, a nationally representative household survey of persons aged 15
      years or older, was conducted for the first time during 2008-2010 in 14 low- and
      middle-income countries. In each country, GATS used a standard core
      questionnaire, sample design, and procedures for data collection and management
      and, as needed, added country-specific questions that were reviewed and approved
      by international experts. The core questionnaire included questions about various
      characteristics of the respondents, their tobacco use (smoking and smokeless),
      and a wide range of tobacco-related topics (cessation; secondhand smoke;
      economics; media; and knowledge, attitudes, and perceptions). In each country, a
      multistage cluster sample design was used, with households selected proportionate
      to the size of the population. Households were chosen randomly within a primary
      or secondary sampling unit, and one respondent was selected at random from each
      household to participate in the survey. Interviewers administered the survey in
      the country's local language(s) using handheld electronic data collection
      devices. Interviews were conducted privately, and same-sex interviewers were used
      in countries where mixed-sex interviews would be culturally inappropriate. All 14
      countries completed the survey during 2008-2010. In each country, the ministry of
      health was the lead coordinating agency for GATS, and the survey was implemented
      by national statistical organizations or surveillance institutes. This article
      describes the background and rationale for GATS and includes a comprehensive
      description of the survey methods and protocol. 

PMID- 24042978
TI  - Left accessory hepatic artery damage by a misplaced gastric band in a deceased
      liver donor.

PMID- 24042979
TI  - Transplant of kidneys from a small pediatric donor with severe rhabdomyolysis.

PMID- 24042980
TI  - Further details from the first human liver transplantation in Europe.

PMID- 24042981
TI  - Early liver transplantation in Europe.

PMID- 24042982
TI  - Fabrication of graphene quantum dots via size-selective precipitation and their
      application in upconversion-based DSSCs.
AB  - A novel approach to synthesize highly luminescent graphene quantum dots (GQDs)
      with well-defined sizes was explored based on simple oxidation of herringbone
      type carbon nanofibers (HCNFs) and size-selective precipitation. 

PMID- 24042983
TI  - Need for a comprehensive epidemiologic study of spinal cord injury in Poland:
      findings from a systematic review.
AB  - STUDY DESIGN: Systematic literature review OBJECTIVE: To review and assess the
      quality of available epidemiologic data of spinal cord injury (SCI) in Poland in
      the context of general International Classification of Functioning (ICF) domains
      and to answer the question whether there is a need for a comprehensive
      epidemiologic study of SCI in Poland. METHODS: Databases Medline, Embase and
      Polish Medical Bibliography were searched using keywords 'spinal cord injury',
      'paraplegia', 'tetraplegia' and 'Poland'. INCLUSION CRITERIA: studies on humans,
      original papers, publication in 1979 or later. Case reports and studies with
      unclear inclusion criteria or performed on a population other than Polish were
      excluded. Full texts were reviewed for data on incidence, prevalence, etiology,
      mortality, natural history and outcome of comprehensive treatment. Quality of
      studies was assessed according to the modified Downs and Black criteria. The ICF
      model was applied to group the studies according to the ICF components. RESULTS:
      Out of 536 identified papers, 224 articles were extracted and reviewed. Mean
      quality score was 11.04 points based on a 28-grade scale. Body functions and
      structures were assessed in 81.6%, activities in 22.4%, participation in 14.8%,
      environmental factors in 15.2% and personal factors in 47% of the studies
      reviewed. CONCLUSION: Current epidemiologic data on SCI in Poland are
      insufficient and biased toward biomedical aspects. There is a need to develop a
      long-term research strategy for SCI in Poland in the form of a comprehensive
      cohort study.

PMID- 24042984
TI  - The correlation between vertebral wedge-shaped changes in X-ray imaging at supine
      and standing positions and the efficacy of operative treatment of thoracolumbar
      spinal fracture in the elderly.
AB  - STUDY DESIGN: By analyzing a large number of surgical patients, we identified the
      roles of wedge-shaped changes in related surgeries. OBJECTIVES: To illustrate the
      relevance of vertebral wedge-shaped changes in X-ray imaging at supine and
      standing positions in patients with percutaneous kyphoplasty as well as the
      postoperative effect. SETTING: All patient data were collected from a hospital in
      China. METHODS: Between June 2006 and May 2010, 77 surgical patients (9 men and
      68 women) with wedge-shaped compression fractures were retrospectively analyzed.
      Patients were divided into group A (DeltaWR?2.5%) and group B (DeltaWR<2.5%)
      according to the dynamic changes in the percentage of vertebral body wedge-shaped
      variable ratio (WR) at supine and standing positions. The intensity of back pain
      in different positions pre- and postoperatively was evaluated with a visual
      analog pain scale (VAS). RESULTS: The WRs in both standing and supine positions
      were significantly reduced by kyphoplasty in both groups A and B. In agreement
      with the improvement in WRs, the VAS was significantly decreased in three
      positions for patients in group A and in turning over and standing position for
      patients in group B. With respect to DeltaWR changes, group B revealed
      significantly lower values compared with group A preoperatively (P<0.001), but
      there was no significant difference between groups A and B postoperatively and at
      1-month follow-up (P=0.179 and P=0.558, respectively). CONCLUSIONS: Improvement
      in symptoms after kyphoplasty is better in patients with wedge-shaped changes in
      supine and standing positions, and the efficacy of height restoration of the
      spine would be better in unstable vertebrae by balloon dilatation.

PMID- 24042985
TI  - History of cervical spine surgery: from nihilism to advanced reconstructive
      surgery.
AB  - STUDY DESIGN: Review of literature. OBJECTIVES: To review and analyze the
      evolution of cervical spine surgery from ancient times to current practice. The
      aim is to present an accessible overview, primarily intended for a broad
      readership. METHODS: Descriptive literature review and analysis of the
      development of cervical spine surgery from the prehistoric era until today.
      RESULTS: The first evidence for surgical treatment of spinal disorders dates back
      to approximately 1500 BC. Conservative approaches to treatment have been the
      hallmark for thousands of years, but over the past 50 years progress has been
      rapid. We illustrate how nations have added elements to this complex subject and
      how knowledge has surpassed borders and language barriers. Transferral of
      knowledge occurred from Babylon (Bagdad) to Old Egypt, to the Greek and Roman
      empires and finally via the Middle East (Bagdad and Damascus) back to Europe.
      Recent advances in the field of anesthesia, imaging and spinal instrumentation
      have changed long-standing nihilism in the treatment of cervical spine
      pathologies to the current practice of advanced reconstructive surgery of the
      cervical spine. A critical approach to the evaluation of benefits and
      complications of these advanced surgical techniques for treatment of cervical
      spine disorders is required. CONCLUSION: Advances in surgery now permit full
      mechanical reconstruction of the cervical spine. However, despite substantial
      experimental progress, spinal cord repair and restoration of lost functions
      remain a challenge. Modern surgeons are still looking for the best way to manage
      spine disorders.

PMID- 24042986
TI  - The potential for functional recovery of upper extremity function following
      cervical spinal cord injury without major bone injury.
AB  - STUDY DESIGN: This was a retrospective observational study. OBJECTIVES: The
      objectives were to describe the prognosis of upper extremity function following
      cervical spinal cord injury (CSCI), and to identify prognostic factors for
      functional recovery. SETTING: Spinal Injuries Center, Japan. METHODS: Sixty
      patients with C3-4 CSCI without major bone injury participated in the study.
      Patients were treated nonsurgically and evaluated using the American Spinal
      Injury Association (ASIA) scales for the upper and lower extremities, their
      residual cervical motor functions, the modified Frankel grade and an upper
      extremity function scale. We compared the findings for the upper extremity
      function scale at 6 months with those for the residual cervical motor functions
      and modified Frankel grade obtained 3 days after injury. RESULTS: Most patients
      with CSCI who could flex their hip and knee from a supine position (95%) or who
      showed some active elbow extension (86%) 3 days after their injury could use a
      spoon at 6 months. We compared patients who used their fingers at 6 months to
      those who could not, and observed significant differences in age and ASIA scores
      for the upper and lower extremities obtained 3 days after injury. A strong
      correlation was observed between the initial motor scores and the extent of
      functional recovery at 6 months. CONCLUSION: Hip and knee flexion from the supine
      position and elbow extension 3 days after injury significantly predicted a
      positive prognosis for upper extremity function. Younger age and higher ASIA
      motor scores obtained 3 days after injury were factors associated with
      neurological recovery.

PMID- 24042987
TI  - Dissociations in the meaning of risk between health-care professionals and
      individuals with spinal cord injury.
AB  - OBJECTIVE: Risks have been a central concern in stem cell research overall, and
      in clinical trials of individuals with spinal cord injury (ISCIs) in particular.
      We sought to elucidate how two important stakeholder groups-health-care
      professionals (HCPs) and ISCIs-view and value both the physical and non-physical
      risks of stem cell interventions. SETTING: The study was conducted in Canada, and
      included participants from both Canada and the United States America. STUDY
      DESIGN: We used semi-structured interviews to gain perspectives on risk from HCPs
      and ISCIs. METHODS: We applied a constant comparative analytic strategy to derive
      themes from the discourse collected through the interviews. RESULTS: We
      identified three major themes about risk from 12 HCP and 24 ISCI participants:
      focus, rationale and approach. The salient components of the themes differed:
      HCPs focus on the physical causes of risks, and the ISCIs on their downstream
      consequences as well as on non-physical risks; HCPs are concerned about evidence,
      and ISCIs about experience; and HCPs approach risk narrowly, whereas the approach
      of ISCIs is more broad and contextualized. CONCLUSION: Although major themes were
      common to the two stakeholder groups, the components of the themes were
      dissociable and illustrate differences in what HCPs and ISCIs worry about, why
      they worry and how they approach their worries. We draw upon these findings to
      make recommendations for improving risk communication and informed consent for
      stem cell research for spinal cord injury.

PMID- 24042988
TI  - Cervical spinal cord injuries without radiographic evidence of trauma: a
      prospective study.
AB  - STUDY DESIGN: Prospective study. OBJECTIVES: In a prospective study, 45
      consecutive cases of cervical spinal cord injury without radiographic evidence of
      trauma (SCIWORET) who were treated non-operatively were analyzed to correlate the
      magnetic resonance image findings with the initial neurological deficit and the
      extent of neurological recovery at 2 years. SETTING: University tertiary-care
      teaching hospital in South India. METHODS: The neurological status of patients
      who did not have any radiographic or computerized tomographic abnormality at the
      time of admission was assessed by ASIA Impairment Scale (AIS) modification of
      Frankel's grading. The spinal cord abnormality seen in the magnetic resonance
      imaging was noted. The neurological status at the end of 2 years was recorded.
      RESULTS: Twenty-seven of the 45 patients (60%) had cord oedema, 8 (17.77%) had
      cord contusion, 8 (17.77%) patients had a normal cord and 2 (4.44%) patients had
      cord swelling on the magnetic resonance image. Out of 27 patients who presented
      with cord oedema, 14 (31.11%) patients recovered from AIS D to AIS E and 6
      (13.33%) patients did not recover and remained at AIS D. Seven (15.55%) patients
      who had a normal cord recovered completely to AIS E. Five (11.11%) patients who
      had contusion of the cord recovered up to AIS D. CONCLUSION: The initial
      neurological status correlates with magnetic resonance imaging findings.
      Subsequent neurological recovery is dependent on the type of cord damage and
      initial neurological status. The rate of recovery and the final motor outcome are
      inversely related to the length of cord involvement.

PMID- 24042990
TI  - Patient Participation in Rehabilitation Questionnaire (PPRQ)-development and
      psychometric evaluation.
AB  - STUDY DESIGN: A cross-sectional postal questionnaire study. OBJECTIVES: The aim
      of the study was to evaluate selected psychometric properties of a draft version
      of the Patient Participation in Rehabilitation Questionnaire (PPRQ) measuring
      patients' experiences of participation in care and rehabilitation. SETTING:
      Sweden. METHODS: On the basis of previous qualitative analyses of patient
      interview data, a 32-item questionnaire covering five domains of participation
      was developed and sent to 268 persons with spinal cord injury, aged 18-80 years
      and injured 1-12 years previously. In total, 141 (51%) evaluable questionnaires
      were returned. Multi-trait analysis was used to assess scaling assumptions by
      testing item convergent and discriminant validity and internal consistency
      reliability (Cronbach's alpha) associated with the hypothesized item-scale
      structure of the questionnaire. RESULT: Nine items failed to meet scaling
      assumptions and were omitted. Scaling assumptions were thereafter substantiated
      for the scales: 'respect and integrity' (6 items); 'planning and decision-making'
      (4 items); 'information and knowledge' (4 items); 'motivation and encouragement'
      (5 items); and 'involvement of family' (4 items). Item-scale correlations ranged
      from 0.67 to 0.85 and most items correlated higher or significantly higher with
      their hypothesized scale than with other scales. Cronbach's alpha was ?0.89 for
      all scales. CONCLUSION: The PPRQ appears to adequately assess central aspects of
      participation in care and rehabilitation from the perspective of patients with
      spinal cord injury. Further studies using larger samples will be undertaken to
      confirm the scale structure as well as the sensitivity and responsiveness of the
      questionnaire.

PMID- 24042989
TI  - MRI evidence that glibenclamide reduces acute lesion expansion in a rat model of
      spinal cord injury.
AB  - STUDY DESIGN: Experimental, controlled, animal study. OBJECTIVES: To use non
      invasive magnetic resonance imaging (MRI) to corroborate invasive studies showing
      progressive expansion of a hemorrhagic lesion during the early hours after spinal
      cord trauma and to assess the effect of glibenclamide, which blocks Sur1-Trpm4
      channels implicated in post-traumatic capillary fragmentation, on lesion
      expansion. SETTING: Baltimore. METHODS: Adult female Long-Evans rats underwent
      unilateral impact trauma to the spinal cord at C7, which produced ipsilateral but
      not contralateral primary hemorrhage. In series 1 (six control rats and six
      administered glibenclamide), hemorrhagic lesion expansion was characterized using
      MRI at 1 and 24 h after trauma. In series 2, hemorrhagic lesion size was
      characterized on coronal tissue sections at 15 min (eight rats) and at 24 h after
      trauma (eight control rats and eight administered glibenclamide). RESULTS: MRI
      (T2 hypodensity) showed that lesions expanded 2.3+/-0.33-fold (P<0.001) during
      the first 24 h in control rats, but only 1.2+/-0.07-fold (P>0.05) in
      glibenclamide-treated rats. Measuring the areas of hemorrhagic contusion on
      tissue sections at the epicenter showed that lesions expanded 2.2+/-0.12-fold
      (P<0.001) during the first 24 h in control rats, but only 1.1+/-0.05-fold
      (P>0.05) in glibenclamide-treated rats. Glibenclamide treatment was associated
      with significantly better neurological function (unilateral BBB scores) at 24 h
      in both the ipsilateral (median scores, 9 vs 0; P<0.001) and contralateral
      (median scores, 12 vs 2; P<0.001) hindlimbs. CONCLUSION: MRI is an accurate non
      invasive imaging biomarker of lesion expansion and is a sensitive measure of the
      ability of glibenclamide to reduce lesion expansion.

PMID- 24042991
TI  - A pilot feasibility study of massage to reduce pain in people with spinal cord
      injury during acute rehabilitation.
AB  - OBJECTIVE: To determine the feasibility of conducting a randomized controlled
      trial of massage therapy for patients with a new spinal cord injury (SCI) during
      acute inpatient rehabilitation. DESIGN: A pilot single-center, randomized, single
      blind, cross-over clinical trial. SETTING: Free-standing, not-for-profit,
      comprehensive rehabilitation center specializing in SCI rehabilitation.
      PARTICIPANTS: Forty adults ages 18 years and older undergoing acute
      rehabilitation following an SCI reporting any type of pain. INTERVENTION:
      Rehabilitation nurses trained to give broad compression massage (BCM) and a
      control light contact touch (LCT) treatments. Participants were randomized to
      receive either BCM or LCT first, in six 20-min treatment sessions over 2 weeks,
      with a 1-week washout between the 2-week treatment periods. MAIN OUTCOME
      MEASURES: Primary outcomes were changes in pain intensity and in fatigue,
      measured daily. Secondary outcomes included depressive symptoms measured by the
      Patient Health Questionnaire-9 (PHQ-9) and an assessment of pain medication
      usage. RESULTS: Pain intensity was higher at baseline and reduced more in the LCT
      first group compared with the BCM-first group in period 1 (P=0.014), although
      this pattern was not found in period 2 (P=0.58). LCT and BCM groups did not
      significantly differ on any secondary measures except PHQ-9. CONCLUSIONS: This
      study demonstrates the feasibility of using rehabilitation nurses to provide
      tactile therapy to patients with an SCI and suggests a model for controlled
      clinical trials examining the efficacy of massage therapies. Although efficacy
      was difficult to assess, BCM was safe and well tolerated.

PMID- 24042992
TI  - Reliability of the revised wheelchair rugby trunk impairment classification
      system.
AB  - STUDY DESIGN: Observational, cross-sectional. OBJECTIVES: A new classification
      system for trunk impairment in wheelchair rugby was introduced in 2010. It
      consists of 10 tests, arranged in an algorithm, to assign four different trunk
      scores (0, 0.5, 1.0 or 1.5) to athletes. The purpose of this study was to assess
      the inter-rater reliability of this classification system. SETTING: National
      competition for wheelchair rugby and wheelchair basketball in the Netherlands and
      Belgium. METHODS: Three experienced wheelchair rugby classifiers independently
      assigned trunk scores to wheelchair rugby and wheelchair basketball athletes in
      two sessions. After each session, test descriptions were adjusted. The inter
      rater reliability was evaluated by determining the agreement and Fleiss Kappa.
      RESULTS: In the first session, all classifiers agreed on the trunk score in 13
      out of 16 athletes; the overall Kappa was 0.76 (P<0.001). The Kappa per trunk
      score ranged from 0.29 to 1. Four test descriptions were adjusted after the first
      session. In the second session, there was an agreement in trunk score between the
      classifiers in 15 out of 21 athletes. The overall Kappa was 0.75 (P<0.0001), and
      the Kappa per trunk scores ranged from 0.58 to 0.92. After the second session,
      two test descriptions were improved. CONCLUSION: The revised classification
      system for trunk impairment in wheelchair rugby showed a adequate inter-rater
      reliability for the allocation of trunk scores.

PMID- 24042993
TI  - Pott's paraplegia secondary to Scrofuloderma is a rare association.
AB  - STUDY DESIGN: Spinal tuberculosis as all other osteoarticular tuberculosis occurs
      as a result of hematogenous dissemination of Mycobacterium tuberculosis from a
      primarily infected visceral focus mainly lungs, but Pott's paraplegia occurring
      secondarily to Scrofuloderma has not been reported till date. PURPOSE: To
      document such an association of Pott's paraplegia and Scrofuloderma. METHODS: A
      29-year-old female presented to us with low backache and paraplegia of 1 month
      duration. Clinical examination showed multiple healed Scrofuloderma lesions over
      sterum and neck (Figure 1). Magnetic resonance imaging (Figure 4), computed
      tomography (Figure 3) and X-ray (Figure 2) showed Pott's spine involving dorsal
      vertebrae (D8-10) with pre and paravetebral abscess with intraspinal extension.
      She was treated by minimally invasive surgery to drain pus and granulation tissue
      by resecting transverse process of D9 vertebra. Drained material was sent for
      histopathological examination, Zielh-neelsen (ZN) staining, culture and
      sensitivity for M. tuberculosis. Patient completely recovered neurologically
      after 1 month of surgery. RESULTS: Patient completely recovered neurologically
      after surgery and is presently on multidrug chemotherapy and spinal brace.
      CONCLUSIONS: Pott's paraplegia can occur secondary to Scrofuloderma and it can be
      managed by multidrug antitubercular therapy and minimally invasive surgical
      procedure.

PMID- 24042994
TI  - Hip abscess due to Aerococcus urinae in a man with paraplegia: case report.
AB  - STUDY DESIGN: Single case report. OBJECTIVE: Present a case of hip abscess
      culture positive for Aerococcus urinae in a man with paraplegia. BACKGROUND:
      Aerococcus species are uncommonly reported and may be misinterpreted as alpha
      streptococci or staphylococci. This organism can cause significant morbidity due
      to urinary tract infection with septicemia or endocarditis. METHODS: Single case
      report. RESULTS: The patient required surgical incision and debridement. Open
      joint inspection was performed, which was complicated by superior dislocation.
      The patient later required a Girdlestone procedure. CONCLUSIONS: A. urinae was
      cultured from a hip abscess in a man with paraplegia. Bacteremia, with the
      bladder as the reservoir, likely led to this abscess. Aerococcus is pathogenic
      and should be considered when culture results reveal unusual staph or strep
      species.

PMID- 24042995
TI  - Using the unbiased perspectives of people living with a spinal cord injury in
      assessments of mobility.
AB  - STUDY DESIGN: Clinometrics study. OBJECTIVE: To devise a way of capturing the
      unbiased perspectives of people living with a spinal cord injury (SCI) in
      assessments of mobility. SETTING: SCI unit and community. METHODS: Three groups
      of raters used the Global Impression of Change Scale (GICS) to rate change in
      mobility of a cohort of patients with a recent SCI. The three groups of raters
      were as follows: 10 people with a recent SCI, 10 people with an established SCI
      and 10 physiotherapists. The ratings were done after viewing 51 pairs of videos
      depicting one of three motor tasks: sitting unsupported, transferring and
      walking. Each pair of videos showed the same person performing the same motor
      task on two occasions. The videos were taken between 1 h and 5 months apart and
      presented side by side, randomly left or right, on the screen. Raters were asked
      to score the amount of change in performance between the two videos on a 7-point
      Global Impression of Change Scale (GICS). Intra-rater reliability for the three
      motor tasks and three groups of raters was determined using intra-class
      correlation coefficients. RESULTS: People with an SCI were reliable at rating
      change in patients' abilities to transfer and walk with ICC's ranging from 0.66
      to 0.81 (95% Confidence interval bounds ranging from 0.51 to 0.94).
      Physiotherapists were consistently but only marginally more reliable at rating
      than people with an SCI. CONCLUSIONS: Videos and the GICS may provide a way of
      using the unbiased perspectives of people living with spinal cord injury in
      assessments of mobility.

PMID- 24042996
TI  - Determination of normative values for 20 min exercise of wheelchair propulsion by
      spinal cord injury patients.
AB  - STUDY DESIGN: This was a retrospective observational study. OBJECTIVE: The
      objective was to determine the normative values for 20 min exercise of wheelchair
      propulsion in spinal cord injury (SCI) subjects. SETTING: Sarah Rehabilitation
      Hospitals Network, Brazil. METHODS: A total of 413 medical records for SCI
      patients at different levels and classifications at the Sarah Rehabilitation
      Hospitals Network, Brazil, who performed 20 min exercise in a rehabilitation
      programme between the years 2004 and 2009 were consulted. Information regarding
      patient and performance characteristics was obtained, including distance
      travelled, mean velocity, rest and exercising heart rate and perceived exertion.
      The data were analysed by gender and by injury level group: tetraplegia (TT) or
      paraplegia (PP). RESULTS: The participants' ages ranged from 18 to 64 years, and
      the median time since injury was 1.2 years. The men and women had different
      performances regardless of their level of injury. The distance ranged between 495
      and 2106 m for men and between 300 and 1901 m for women. The mean velocity of
      propulsion ranged from 25 to 105 m min(-1) for men and from 15 to 95 m min(-1)
      for women. CONCLUSIONS: This study provides normative data for the 20 min
      exercise that could be used to estimate the resistance capacity by manual
      wheelchair users with SCI and evaluate the effects of training and other
      therapeutic interventions.

PMID- 24042997
TI  - The chemical chaperon 4-phenylbutyric acid ameliorates hepatic steatosis through
      inhibition of de novo lipogenesis in high-fructose-fed rats.
AB  - Non-alcoholic fatty liver disease caused by dietary factors such as a high
      fructose intake is a growing global concern. The aim of this study was to
      investigate the intervention effects of an endoplasmic reticulum stress (ERS)
      inhibitor 4-phenylbutyric acid (PBA) on liver steatosis induced by high-fructose
      feeding in rats and the possible underlying mechanisms. Wistar rats were divided
      into the control, high-fructose group (HFru) and PBA intervention (HFru-PBA)
      groups. PBA intervention was initiated following 4 weeks of high-fructose
      feeding. After 8 weeks of feeding, the ERS markers p-PERK, p-eIF2alpha, p-IRE-1,
      spliced XBP-1, ATF-6 were measured by western blotting. Liver triglyceride
      contents and morphological changes were examined. The protein expression of
      lipogenic key enzymes (ACC, FAS and SCD-1) and upstream transcriptional factors
      (SREBP-1c and ChREBP) were measured. The ERS-related cell events, oxidative
      stress and apoptosis, were evaluated by standard methods. Results demonstrated
      that PBA intervention significantly resolved hepatic ERS and improved liver
      steatosis induced by high-fructose feeding in rats. The protein expression of
      ACC, FAS, SCD-1 and SREBP-1c was upregulated in high-fructose-fed rats, whereas
      it decreased following PBA intervention. Oxidative stress and apoptosis were
      observed in livers of high-fructose-fed rats, but were alleviated by PBA
      intervention. ERS is involved in the development of fatty liver induced by a high
      fructose intake. ERS inhibition by PBA can therefore ameliorate liver steatosis
      through inhibition of hepatic lipogenesis.

PMID- 24042998
TI  - Therapeutic modalities in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease with
      significant clinical heterogeneity. Its pathogenesis is complex and involves
      multigenic components, dysregulation of T and B lymphocytes and the presence of
      autoantibodies, which form the basis for inflammation, and the pathology found in
      the various organ systems. Traditional treatments for SLE have included non
      steroidal anti-inflammatory drugs, antimalarials, corticosteroids, and
      cytotoxic/immunosuppressants, but a recent emphasis on the development of
      biological agents that inhibit autoreactive B cells, interrupt cytokine signaling
      and facilitate the development of regulatory T cells has become a new modality in
      treating the disease. This review will delve into the pathogenesis of the disease
      process, as well as the current and up and coming novel biological treatment and
      other therapies for specific disease manifestations, such as neuropsychiatric SLE
      and cutaneous lupus erythematosus, and detail the shift to immune targeted
      therapies and novel treatments being developed for specific manifestations of the
      disease. 

PMID- 24042999
TI  - Paddlewheel multi-slice helical computed tomography reformation in the detection
      of pulmonary embolism. An initial experience.
AB  - OBJECTIVE: To assess the value of paddlewheel multi-slice helical CT techniques
      in the detection of pulmonary embolism (PE). METHODS: A prospective study was
      conducted from December 2011 to February 2013 at the Radiology Department, Dallah
      Hospital, Riyadh, Kingdom of Saudi Arabia. The CT scans of 71 patients presented
      for CT pulmonary angiography were selected and interpreted by 2 radiologists
      using reformatted paddlewheel technique besides coronal multiplanar volume
      reconstruction (MPVR). Paddlewheel reconstruction was carried out using inbuilt
      software on sagittal and axial images, setting 5 and 2 mm slab thickness with 5
      and 2 degree angle rotation. Reference standard was overall interpretation of
      coronal MPVR and paddlewheel reformatted images by both radiologists. RESULTS: In
      71 patients (44 were females and 27 were male) with suspected PE, 43 were found
      to be positive, and 28 were found to be negative. The youngest patient was 15
      years old, and the oldest was 99 years of age. Paddlewheel reformatted images
      display significantly high sensitivity and specificity in eliciting total number
      of pulmonary emboli compared to coronal MPVR by detecting 51 additional emboli.
      Decreasing slab thickness and rotation angle enhanced sensitivity of paddlewheel
      reformatted images by detecting another 11 emboli. CONCLUSION: The paddlewheel CT
      angiography technique with fine slice thickness and less rotational angle
      enhances PE imaging.

PMID- 24043000
TI  - The role of 3-dimensional echocardiography in evaluating congenital heart
      diseases.
AB  - OBJECTIVE: To assess the feasibility and efficacy of the real-time transthoracic
      3-dimensional echocardiography (RTT-3DE) technique in providing more detailed
      information compared to 2-dimensional echocardiography (2DE) in patients with
      structural heart disease, and to explore its application in routine clinical use.
      METHODS: This cross sectional study was carried out at the Prince Sultan Cardiac
      Center, Riyadh, Kingdom of Saudi Arabia from January to June 2009. Patients with
      congenital heart disease (CHD) were evaluated by conventional 2DE followed by RTT
      3DE using dedicated software and a standard protocol. The 3DE studies were graded
      as: A--new finding not on 2DE; B--useful anatomic perspective; C--equivalent to
      2DE; or D--missed 2DE findings. RESULTS: Fifty patients, 29 (58%) males and 21
      (42%) females with age range from one month to 17 years compose the study group.
      The 2DE showed 12 (24%) right heart and 18 (36%) left heart lesions, 12 (24%)
      septal defects, one (2%) aortopulmonary window, 4 (8%) complex CHD, and 3 (6%)
      borderline left ventricular volume. When compared with the 2DE studies, 3DE
      studies were graded A in 25, B in 24, and C in one case. CONCLUSION: The results
      in this study show that the RTT-3DE technique is feasible and very effective in
      providing more detailed information compared with 2DE in structural heart disease
      evaluation.

PMID- 24043001
TI  - Anatomical variation of brachial artery bifurcation.
AB  - OBJECTIVE: To observe the topographic localization of the brachial artery
      termination. METHODS: This study was conducted at the Department of Anatomy,
      Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
      from December 2011 to February 2013. The bifurcation level of the brachial artery
      was determined in relation to the neck of the radius. Normal and abnormal
      terminations of the brachial artery were recorded. RESULTS: In 13 cases (21.7%),
      the bifurcation of brachial artery was normal. In 33 cases (6%), the bifurcation
      level was a few centimeters below the neck of the radius. In 7 cases (11.7%), the
      bifurcation level was above the radial neck in the area of cubital fossa. In 6
      cases (10%), the termination of the brachial artery was found to be above the
      middle of the front of the arm. In one of the previous cases, the radial artery
      arose from the brachial artery on the medial side of the ulnar artery. In one
      case (1.7%), the radial and the ulnar arteries originated directly from the
      axillary artery, the brachial artery was absent. CONCLUSION: Morphological
      variations of the brachial artery are common findings and should be considered by
      surgeons when performing procedures in the brachial artery area.

PMID- 24043002
TI  - Visual outcomes and patient satisfaction after implantable collamer lens and
      Toric implantable collamer lens correction for moderate to high myopia and myopic
      astigmatism.
AB  - OBJECTIVE: To compare preoperative and postoperative visual outcomes, determine
      patient's satisfaction, and evaluate visual symptoms after implantable collamer
      lens (ICL) implantation. METHODS: One hundred and twelve patients with myopia
      between -2.75 and -19.50 diopter had ICL or Toric ICL (TICL) implantation. The
      implantations were carried out at the Cornea and Refractive Unit, Magrabi Eye
      Hospital, Sana'a, Republic of Yemen between September 2007 and October 2010.
      Preoperative and postoperative uncorrected visual acuity (UCVA), best spectacle
      corrected visual acuity (BSCVA), and refraction was evaluated. Patient's
      satisfaction and visual symptoms were evaluated using a questionnaire. RESULTS:
      The mean age was 26.74 +/- 5.6 years. The mean preoperative UCVA improved from
      0.01 +/- 0.04 to 0.75 +/- 0.22. The mean postoperative UCVA (0.75 +/- 0.23)
      versus preoperative BSCVA (0.61 +/- 0.23) had a significant statistical change
      (p<0.001), and Pearson correlation of 0.818. Preoperative BSCVA versus
      postoperative BSCVA gained 5 lines in 2.5%, 4 lines in 4.4%, 3 lines in 14.2%, 2
      lines in 32.8%, and one line improvement in 24%, whereas it was maintained in
      20.1%, and lost one or more lines in 2%. The mean score for the overall
      satisfaction was 2.67 +/- 0.45. A total of 15.2% reported complaint of halos,
      13.4% reported perception of stars around lights, and 23.2% had glare.
      CONCLUSION: Implantation of ICL and TICL is safe and effective and provides
      predictable refractive results with good satisfaction in the treatment of
      moderate to high myopia, suggesting its viability as a surgical option for the
      treatment of myopia.

PMID- 24043003
TI  - The ideal aesthetic nasal dorsum in the Saudi population.
AB  - OBJECTIVE: To investigate and define the ideal aesthetic nasal dorsum measurement
      in the Saudi population. METHODS: This observational study was conducted from
      January to December 2012 at the Department of Otolaryngology, Head and Neck
      Surgery, King Abdulaziz University Hospital, King Saud University, Riyadh,
      Kingdom of Saudi Arabia. A total of 127 raters, 56 males and 71 females were
      asked to choose the most ideal profile view from one male and one female
      photograph, whose nasolabial angle were fixed at 90 degrees for the male, and 95
      degrees for the female, and whose level of dorsum was modified with a Photoshop
      program into 5 variables in relation to a line drawn from the radix to the tip
      defining points (anterior of more than 2 mm anterior within 2 mm, at the level of
      the line, posterior within 2 mm, and posterior of more than 2 mm). RESULTS: Male
      raters preferred the dorsal level slightly posterior within 2 mm (57.1%) for the
      male photograph, and a straight dorsum (58.9%) for the female photograph. For
      female raters, the slightly concave profile of less than 2 mm was the most
      preferred (71.8%) in males, while for females they gave an equal score for either
      straight dorsum or posteriorly within 2 mm (47.9%). CONCLUSION: The findings in
      this study conclude that males preferred a male of a slight deep dorsum, and a
      female of a straight profile line. Females preferred the male of slight deep
      dorsum and a female of a straight profile, or slight concavity.

PMID- 24043004
TI  - Arabic coffee increases the glycemic index but not insulinemic index of dates.
AB  - OBJECTIVE: To determine whether the glycemic index (GI) and insulinemic index
      (II) of dates could be altered by Arabic coffee consumption. METHODS: This
      randomized cross-over study was conducted at the Department of Nutritional
      Sciences, Faculty of Health and Medical Sciences, University of Surrey,
      Guildford, United Kingdom from November 2009 to February 2010. Healthy subjects
      (5 males, 5 females) were recruited to the study. They were fed Khulas dates
      either with water, or with Arabic coffee. Plasma glucose and insulin responses
      were measured using standardized methods. Responses were compared with a pure
      glucose solution matched for available carbohydrate. The GI and II were
      calculated using standardized methods, and results were presented as means and
      standard error of mean. Glucose and insulin responses were compared using
      repeated measures analysis of variance. RESULTS: The GI of dates was 55 +/- 6,
      which increased to 63 +/- 5 for dates consumed with Arabic coffee (p=0.08). No
      significant difference was observed between the II for dates, and the II of dates
      consumed with Arabic coffee (p=1.00). CONCLUSION: Arabic coffee consumption
      modestly increased the plasma glucose response of dates compared to that of dates
      consumed with water. Insulin levels were not significantly affected. The modestly
      higher glycemic response to dates in the presence of Arabic coffee indicates that
      this custom may be considered detrimental to health.

PMID- 24043005
TI  - Prevalence and distribution of metabolic syndrome in a southern Chinese
      population. Relation to exercise, smoking, and educational level.
AB  - OBJECTIVE: To investigate the prevalence and distribution of metabolic syndrome
      (MetS) and the impact of exercise, smoking, and educational level on the risk of
      MetS in a southern Chinese population. METHODS: A cross-sectional study was
      conducted in Zhuhai City, China from June to August 2012. Data on exercise,
      smoking, and educational level, anthropometric parameters, blood pressure, lipid,
      and glucose levels were collected. The prevalence of MetS (as defined by the
      International Diabetes Federation) was determined. Data necessary to evaluate
      MetS, the socio-economic characteristics, and lifestyle were obtained for 4645
      subjects aged 18-75 years old. RESULTS: A total of 19.8% of the participants had
      MetS. The adjusted odds of having MetS were lower among males (adjusted odds:
      0.75; 95% confidence interval [CI]: 0.57-1.01) compared with females. Those
      participants who currently smoked had a higher risk of developing MetS compared
      with non-smokers (adjusted odds: 1.61; 95% CI: 1.13-2.50). Those who had no
      physical exercise had a higher risk of developing MetS compared with those who
      physically exercised more than 60 minutes/day (adjusted odds: 1.51; 95% CI: 1.12
      2.23;). Compared with those with no education, every category of attained
      educational level had a lower risk of developing MetS (p<0.001). CONCLUSION: The
      findings in this study revealed that current smokers had a greater risk of
      developing MetS compared with non-smokers. Increased physical activity and higher
      levels of education attained served as protective factors for the population.

PMID- 24043006
TI  - The value of urine cytology in the diagnosis of bladder cancer. Cytopathological
      correlation.
AB  - OBJECTIVE: To identify the value of urine cytology in the diagnosis of bladder
      cancer by comparing cytologic and histologic findings. METHODS: This study was
      conducted from January to December 2012 at the Department of Pathology, Faculty
      of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia. The
      laboratory database was retrospectively reviewed for all patients with a
      histopathological diagnosis of urothelial carcinoma (UC) between January 2007 and
      December 2011. Histopathological diagnosis was considered the gold standard, and
      urine cytology findings were correlated with the results of bladder biopsy.
      Biopsies with low- and high-grade lesions were considered positive. All data were
      analyzed using the Statistical Package for Social Sciences. RESULTS: We reviewed
      the results of 191 patients. Urine cytology results were positive for malignancy
      in 70 cases (36.6%) and negative in 19 (9.9%). One hundred and two cases (53.4%)
      were considered suspicious for malignancy. Histopathological examination revealed
      that there were 82 cases (42.9%) of low-grade UC, and 64 cases (33.5%) of high
      grade UC. Seven cases (3.7%) were positive for malignancies other than UC. For
      urine cytology, the overall sensitivity was 94.1%, and 26.3% specificity. The
      sensitivity of urine cytology for low-grade was 18.3%, and 51.3% for high-grade
      UC. The specificity for both grades was 26.3%. CONCLUSION: This study shows that
      sensitivity of urine cytology is higher in high-grade UC than in low-grade UC.
      The high sensitivity of urine cytology confirms that it is still a valuable tool
      in bladder cancer diagnosis.

PMID- 24043007
TI  - Identification of Helicobacter pylori by different conventional staining
      techniques and its comparison with polymerase chain reaction.
AB  - OBJECTIVE: To evaluate Helicobacter pylori (H. pylori) detection by histological
      staining methods, and to compare with those of Gram staining and polymerase chain
      reaction (PCR). METHODS: This is a cross-sectional study conducted at the
      Department of Microbiology, Shree P. M. Patel Paramedical College, Anand,
      Gujarat, India on 436 patients attending the Deep Surgical Hospital, Anand,
      Gujarat between February 2008 and October 2011. Biopsies were subjected to
      histological staining using Hematoxylin & Eosin (H&E), Giemsa, and Warthin-Starry
      stains, as well as with Gram staining. The PCR was performed on 71 biopsy
      samples. RESULTS: Sensitivity and negative predictive values of all 3
      histological stains (Warthin-Starry, H&E, and Giemsa) were excellent. Gram
      staining showed excellent results pertaining to sensitivity, specificity,
      positive predictive value, and accuracy. Sensitivity of PCR was remarkably low
      compared to all the staining methods. The sensitivity of all histological stains
      was found better than PCR. CONCLUSION: From the findings in our study, we
      conclude that in a mediocre laboratory, where PCR facility is not available,
      histological stain can be a better substitute for the diagnosis of H. pylori. Our
      findings also confirm the assertion that Gram staining is a preferred stain,
      affordable, reliable, and simple means for identifying H. pylori compared with
      both histology and PCR.

PMID- 24043008
TI  - Effects of infants' birth order, maternal age, and socio-economic status on birth
      weight.
AB  - OBJECTIVE: To determine the effects of infants' birth order, maternal age, and
      socioeconomic status (SES) on birth weight. METHODS: This cross-sectional study
      included a sample of 858 mothers recruited over a 6-month period in 2010, in a
      defined population of 9 urban health centers, and who were admitted for their
      infants' first vaccination. Maternal clinical data, demographic data, and
      infants' birth weight were obtained from the interview and maternal hospital
      files. Multiple regression and analysis of variance were used for data analysis.
      RESULTS: First and fourth births had lower birth weights compared with second and
      third births in all maternal ages in controlling parity, birth weight increases
      with maternal age up to the early 24, and then tends to level off. Male gender,
      maternal age 20-24 years, second and third births had a significant positive
      effect on birth weight. Lower family economic status and higher educational
      attainment were significantly associated with lower birth weight. For women in
      the 15-19 and 40-44 years age groups, the second birth order was associated with
      the most undesirable effect on birth weight. CONCLUSION: Accessibility of health
      care services, parity, maternal age, and socioeconomic factors are strongly
      associated with infants' birth weight.

PMID- 24043009
TI  - Evaluation of biomedical research in Saudi Arabia.
AB  - OBJECTIVE: To evaluate the quality and quantity of biomedical studies published
      in the Kingdom of Saudi Arabia (KSA) between 2010 and 2011. METHODS: This study
      was conducted on January 2013 at the Internal Medicine Department, Taif
      University, Taif, KSA. An online search was conducted on PubMed to collect the
      articles published from KSA using the country name (Saudi Arabia) as a keyword.
      The search was limited to studies published in the period of 2 years from January
      2010 to December 2011. The year 2012 was not included to give at least one year
      for citation. The total number of studies during the stated period was compared
      with those published from other countries in the same period, and adjusted per
      population size. Impact factor and number of citations were used to assess the
      quality of the studies. RESULTS: A total of 1905 published articles/studies were
      from KSA in the said period. Australia had the maximum number of studies (100%)
      published per million population (1258.571+). The KSA had 72.71 articles per
      million population, and was ranked 16th among the other countries. Most of the
      articles (65.3%) were published from Riyadh followed by Jeddah (13.3%), and most
      of them were from the fields of Community Medicine (15.5%), Pathology (13.7%),
      Medicine (13.2%), and Surgery (13.1%). King Faisal Specialist Hospital in Riyadh
      had the highest impact factor with a mean of 2.74 +/- 3.45. CONCLUSION: The
      Kingdom of Saudi Arabia is lagging behind in biomedical research. While King
      Faisal Specialist Hospital and Research Centre appears to be doing better than
      other institutions in biomedical research, there is an urgent need for greater
      investment in biomedical research in the kingdom.

PMID- 24043010
TI  - Concurrent splenic lymphangiomatosis and Proteus syndrome.
AB  - A 37-year-old female presented with Proteus syndrome and was found to have an
      asymptomatic enlarged spleen. Pathology confirmed splenic lymphangiomatosis. We
      describe an association of these 2 disorders in the Middle Eastern population.
      Diagnosis and pathogenesis are discussed in this case report. 

PMID- 24043011
TI  - Single implant in the mandibular molar region of edentulous patient.
AB  - Implant-retained overdentures are a valid treatment option for edentulous
      patients, especially for patients with severe alveolar ridge atrophy. A central
      single implant is considered adequate to retain an overdenture in the edentulous
      mandible. However, for some patients, there is no sufficient bone height, or
      width in the interforaminal region of the mandible for insertion of the implant.
      This case report illustrates that the insertion of a single implant in the
      mandibular molar region might stabilize the prosthesis, and might improve the
      oral health-related quality of life and chewing function. A Locator attachment
      was used in this case to retain the overdenture. The one-year clinical results
      are promising. However, long-term clinical results and randomized clinical trials
      are needed before this method can be widely used in clinical application. 

PMID- 24043012
TI  - Severe pulmonary tuberculosis complicating intestinal tuberculosis with the
      entire colorectal ulcers.

PMID- 24043013
TI  - Rescue intubation by combined use of video laryngoscopy and Bonfils fiberscope in
      patients with difficult airway.

PMID- 24043014
TI  - Dual-functional hetero-structured TiO2 nanotrees composed of rutile trunks and
      anatase branches for improved performance of quantum dot-sensitized solar cells.
AB  - We developed a two-step hydrothermal method to prepare hetero-structured TiO2
      nanotree arrays on FTO substrates. This process included the deposition of rutile
      nanorod arrays with a length of about 2 MUm as trunks at first and then the
      growth of the anatase nanosheets with the thickness of less than 10 nm standing
      on the rutile trunks through a dissolution-growth process. After being coated
      with CdS and CdSe quantum dots, these nanotrees were used as photoanodes in the
      quantum dot-sensitized solar cells (QDSSCs). It was found that the branches could
      enlarge the surface area of the anode, increase the amount of the deposited
      quantum dots, and thus improve the light absorption of the whole device.
      Moreover, the electron transport dynamics indicated that the phase junctions
      between the rutile trunks and anatase nanosheets could accelerate the electron
      transport in the QDSSCs. As a result, we got a conversion efficiency of ~2.4%
      with the thickness of less than 2 MUm, which was 50% higher than that in the
      nanorod array-based QDSSCs.

PMID- 24043015
TI  - Identifying Biologically Meaningful Groups of Genes in the Androgen Receptor
      Network.

PMID- 24043016
TI  - An Experimental Setup for Instrumental Analysis of Femoral Derotation Osteotomy.

PMID- 24043018
TI  - Genome Assembly Framework on Massively Parallel, Distributed Memory
      Supercomputers.

PMID- 24043019
TI  - A Framework for Multi-Model Surgical Workflow Management.

PMID- 24043017
TI  - Telemonitoring for COPD Patients: Standardized Bluetooth Interface Between
      Medical and Mobile Devices.

PMID- 24043020
TI  - Integrative Analysis of -Omics Data: A Method Comparison.

PMID- 24043021
TI  - Workflow-Supported Biosignal Integration in Multimodal Clinical Trials.

PMID- 24043022
TI  - Development of a Communication Server for Long-Term Telemonitoring of Patients
      with COPD.

PMID- 24043023
TI  - Automated Detection of Human Brain Tumors Using in Vivo 1H MR Spectra of Healthy
      Brain Tissue.

PMID- 24043024
TI  - A Healthcare Supply Chain Solution for Dental Purposes.

PMID- 24043025
TI  - Harvesting Patient Opinions about Implants from Social Media Sources.

PMID- 24043026
TI  - Chordoma Low-Template Microarray Analysis.

PMID- 24043028
TI  - Patient Individual Parameterization of Cardiac Ventricular Tachycardia
      Termination Algorithm.

PMID- 24043027
TI  - Prototypical Development of a Remote Patient Monitoring System for Efficient
      Treatment of COPD Patients.

PMID- 24043029
TI  - A Clinical Metabolomics Strategy to Discover New Biomarkers in Complex Disease:
      An Overview.

PMID- 24043030
TI  - Simulation of Cell-Laden Flow in a Cell Mixer Using Computational Fluid Dynamics.

PMID- 24043031
TI  - Feasibility Check of OPTO-Electronic Volumetric Measurements Utilizing the i-Lung
      Model.

PMID- 24043032
TI  - Differences in blood velocity simulated stented vessels between pulsed and
      laminar blood flow: An evaluation using numerical fluid dynamics (CFD).

PMID- 24043033
TI  - A Sensitivity Analysis of Stent Design Parameters using CFD.

PMID- 24043034
TI  - Impact of Different Ablation Patterns on the Biomechanics of the Human Left
      Atriijm.

PMID- 24043035
TI  - A Family of Physiological Models to Simulate Human Gas Exchange.

PMID- 24043036
TI  - Impact of hERG Mutations on Simulated Human Atrial Action Potentials.

PMID- 24043037
TI  - Effects of Brownian Motion on Electrical Double Layer.

PMID- 24043038
TI  - Selection Criteria for Competing Models of Respiratory Mechanics.

PMID- 24043039
TI  - Pressure Cost of Volume Delivery In HFOV at Different Ventilatory Frequencies.

PMID- 24043040
TI  - In Silico Medicine Approach to Predict Changes in Human Vertebrae Due to
      Osteoporosis and Treatment.

PMID- 24043041
TI  - Electromechanical Modeling of the Human Atria.

PMID- 24043042
TI  - Dental Ultrasound Diagnostics - a Simulation Study.

PMID- 24043043
TI  - Response of the adjacent bone tissue on open-porous scaffolds applied for
      segmental defects - numerical simulation of bone remodelling.

PMID- 24043044
TI  - Transfer Function Identification of a New Active Lung Simulator Concept for
      Precise Motor Control.

PMID- 24043045
TI  - Estimating Intracellular Conductivity Tensors from Confocal Microscopy of Rabbit
      Ventricular Tissue.

PMID- 24043046
TI  - Visualisation of Time-Variant Respiratory System Elastance in ARDS Models.

PMID- 24043048
TI  - Effects of Tip-Applicator Positioning on Recorded Temperature Profiles in
      Cryoablation Procedures Estimated by Finite Element Modeling.

PMID- 24043047
TI  - Quantification and Localization of Extended Nanoparticle Distributions in Tissue
      Using Multipole Expansion.

PMID- 24043049
TI  - Comparison of Model Based and Clinical Blood Glucose Evolution during and after
      Anhepatic Status.

PMID- 24043050
TI  - Computational Challenges in Building Multi-Scale and Multi-Physics Models of
      Cardiac Electro-Mechanics.

PMID- 24043051
TI  - Protraction Effects in a Stochastic Cell-Cycle Tumor Model Exposed to
      Fractionated Radiotherapy.

PMID- 24043052
TI  - Determination of the Optical Properties of Native Joint Cartilage with NIR -
      Spectroscopy.

PMID- 24043053
TI  - Simulation of Cardiac Radiofrequency Catheter Ablation - the Importance of
      Working Angle.

PMID- 24043054
TI  - Verification of the Thermal Properties of the Electronic Skin.

PMID- 24043055
TI  - A Quasi-Stationary Approach to the Approximate Solution of an FEA 3D Subject
      Specific EMG Model.

PMID- 24043056
TI  - Evaluation of a Model based Optimization Algorithm for Pressure Controlled
      Ventilation.

PMID- 24043057
TI  - Perturbation fields of arbitrary homogeneous magnetic spheroids in a homogeneous
      magnetic field.

PMID- 24043058
TI  - Integration of Patient Specific MRI Imaging Data Into a Stochastic Low-Grade
      Glioma Model.

PMID- 24043059
TI  - Modelling and Simulation of an In-Vitro Experimental Setup to Determine Membrane
      Electric Properties.

PMID- 24043060
TI  - Tissue Structure and Ca2+-Mediated Ectopic Beats.

PMID- 24043061
TI  - Finite Element Study of the Accommodation Behaviour of The Crystalline Lens after
      fs-Laser Treatment.

PMID- 24043062
TI  - Robustness Analysis of a Mathematical Gas Exchange Model.

PMID- 24043063
TI  - Adaptation of the Voltage Dependent Muscarinic M2 Receptor on Cardiac Ik,Ach to
      Different Ligands.

PMID- 24043064
TI  - Simulation of the Conjunctival and Choroidal Blood Flow Using a New Multi-Layer
      Diffusion Cell.

PMID- 24043065
TI  - A Computer Model for Single-Breath Washout with Double-Tracer Gas to Help
      Understanding Ventilation Inhomogeneity.

PMID- 24043066
TI  - Influence of Skull Defects on MEG Source Reconstruction in an In-Vivo Animal
      Experiment.

PMID- 24043067
TI  - Simulating the Mechanics of Myocardial Tissue Using Strongly Scalable Parallel
      Algorithms.

PMID- 24043068
TI  - Fem-Driven Parameter Optimization of an Electrochemotherapy Catheter Prototype.

PMID- 24043069
TI  - Computation of Muscle Fiber Contraction Dynamics.

PMID- 24043070
TI  - Influence of Catheter Orientation, Tissue Thickness and Conduction Velocity on
      the Intracardiac Electrogram.

PMID- 24043071
TI  - Tidal Volume Dependence on the Ventilatory Frequency and Alveolar Compliance in
      HFOV.

PMID- 24043072
TI  - Changes of the Electric Field Distribution in the Femoral Head Due to Position
      and Design of an Electro-Stimulating Implant.

PMID- 24043073
TI  - Predicting etCO2 Response in a Model of Ventilation-Perfusion Mismatch.

PMID- 24043074
TI  - Comparison of Telemedical and Conventional Treatment of Heart Failure Patients
      Considering Different Approaches to In-Hospital Stay.

PMID- 24043075
TI  - Variation of Human Ventricular Iks Heterogeneities to Reconstruct Measured Multi
      Channel ECG Data.

PMID- 24043076
TI  - Simulation of the Ultra-Short Sleep-Wake Protocol Using the Two Process Model.

PMID- 24043077
TI  - Simulation of the Temperature Distribution in Protein Solder and Cartilage - Bone
      - Tissue by Laser Soldering.

PMID- 24043078
TI  - Mechanical Properties of a Photopolymerizable Hydrogel for Intervertebral Disc
      Replacement.

PMID- 24043079
TI  - Implantable Silicone Electrode for Measurement of Muscle Activity: Results of
      First in Vivo Evaluation.

PMID- 24043080
TI  - Satisfaction of Prosthesis Users with Electrical Hand Prostheses and their
      Sugggested Improvements.

PMID- 24043081
TI  - Mikrosystemintegration im Herausnehmbaren Zahnersatz.

PMID- 24043082
TI  - A Substrate Isolated LDO for an Inductively Powered Retinal Implant.

PMID- 24043083
TI  - A Novel Bioactive Implant Material Based on a Porous Siliconehydrogel- Composite.

PMID- 24043084
TI  - A setup for ultrasound based assessment of the aortic root geometry.

PMID- 24043085
TI  - Investigating the Applicability of Fluidized-Bed Technology for High-Throughput
      Coating of Stents.

PMID- 24043086
TI  - Minimal Invasive Pelvic Neuromonitoring - Technical Demands and Requirements.

PMID- 24043087
TI  - Development and evaluation of a silicone-based ferrite cover to optimize the
      transmission-characteristics of telemetric interfaces for active medical
      Implants.

PMID- 24043088
TI  - Impact of Crimping Procedure and Storage on the Mechanical Performance of
      Peripheral Drug-Eluting Stents.

PMID- 24043089
TI  - In Vitro Rabbit Drug Cytotoxicity Model for Fibrosis Prevention in Glaucoma
      Surgery.

PMID- 24043090
TI  - Enhanced power management unit for the Artificial Accommodation System.

PMID- 24043091
TI  - Biocompatibility Material Test for Cardiovascular Devices using Stagnation Point
      Flow.

PMID- 24043092
TI  - Feasibility of Polymer/Drug Coating on Absorbable and Permanent Stent Platforms -
      Technological Challenges.

PMID- 24043093
TI  - A Novel Total Artificial Heart for Destination Therapy: In-Vitro and In-Vivo
      Study.

PMID- 24043094
TI  - Development of Multi-Channel Intramuscular EMG Recording Electrodes.

PMID- 24043095
TI  - Online Detection of Stent Fractures in Durability Tests by Monitoring the
      Electrical Resistance.

PMID- 24043096
TI  - A High-Voltage Neural Stimulator Combined with a Low-Voltage Recorder.

PMID- 24043097
TI  - Determination of Geometry Parameters of the Ossicular Chain Based on 3D Models
      from Micro-Ct-Scans.

PMID- 24043098
TI  - Comparison of Different Conductive Fillers in Silicone for the Purpose of
      Replacing Metallic Conductive Structures in Flexible Implants.

PMID- 24043099
TI  - Low-Cost Head Phantom for the Evaluation and Optimization of Rf-Links in
      Ophthalmic Implants.

PMID- 24043100
TI  - Non-Invasive detection of the Influence of Spasticity on Muscular Activation.

PMID- 24043101
TI  - A Vibrotactile Assistive System for Directional Navigation.

PMID- 24043102
TI  - Guiding Visually Impaired People by Transmitting Navigational Instructions to
      Wearable Vibrating Belt Systems.

PMID- 24043103
TI  - Concept of a Co-Adaptive Training Environment for Human-Machine Interfaces Based
      on EMG-Control.

PMID- 24043104
TI  - A Novel Portable System for Gait Analysis and Rehabilitation.

PMID- 24043105
TI  - Patient Situation Recognition Framework for an end Effector Based Rehabilitation
      System.

PMID- 24043106
TI  - Development of a Software Package to Assess and Analyze Gait Data Gathered by the
      Eshoe System.

PMID- 24043107
TI  - Identification of relevant clinical symptoms for the development of a machine
      aided screening method of postural deformities.

PMID- 24043108
TI  - Next Generation Surgical Instruments Powered by Hydraulics.

PMID- 24043109
TI  - Miniaturized Haptic User-Interface for Heart Catheterizations - Concept and
      Design.

PMID- 24043110
TI  - Removal of Small-Sized Kidney Stones Fragments Using Inverted Flushing Procedure
      in Ureteroscopy.

PMID- 24043111
TI  - A Model to Investigate the Urinary Bladder's Thermal Behaviour during
      Transurethral Resection of Prostate Tissue.

PMID- 24043112
TI  - Development of a Cable Actuated Joint for a Surgical Robotic Flexible Arm.

PMID- 24043113
TI  - Use of 3 Dimensional Models and Navigation System in Preparation for Brain
      Surgery.

PMID- 24043114
TI  - Powerful Micro-Actuators for (Flexible) Surgical Instrument Tips.

PMID- 24043116
TI  - 7,8-dihydroxycoumarin may promote sciatic nerve regeneration by suppressing NF
      kappaB expression in mice.
AB  - Nuclear factor (NF)-kappaB expression occurs during sciatic injury. In addition,
      7,8-dihydroxycoumarin exhibits a neurotrophic effect on peripheral nerve
      regeneration. To investigate the effects of 7,8-dihydroxycoumarin on the
      expression levels of NF-kappaB in L4-6 spinal cord segments of the injured
      sciatic nerve in mice and on the functional recovery and regeneration following
      nerve injury, a total of 160 healthy adult male BALB/c mice underwent unilateral
      sciatic nerve interruption and anastomosis. The mice were separated into groups
      and subsequently treated with physiological saline (control) or high, medium or
      low doses of 7,8-dihydroxycoumarin. NF-kappaB levels were detected by western
      blot analysis and quantitative polymerase chain reaction (qPCR), and the sciatic
      functional index (SFI) was measured. Neuronal apoptosis was detected by terminal
      deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) staining.
      The results revealed that NF-kappaB was activated in the L4-6 spinal cord
      connected to the injured sciatic nerve. qPCR and western-blot analysis results
      showed that the expression levels of NF-kappaB in the high- and medium-dose
      groups were significantly lower compared with the low-dose and control groups at
      12 h, one day, three days, five days and one week (P<0.05 for each). SFI and
      TUNEL results demonstrated that the high- and medium-dose groups exhibited
      improved functional nerve regeneration and reduced apoptosis compared with the
      low-dose and control groups. In conclusion, 7,8-dihydroxycoumarin is capable of
      suppressing the immune activation of NF-kappaB in the neurons of the L4-6 spinal
      cord connected with the injured sciatic nerve, thereby reducing the focal
      filtration of inflammatory cells, producing the optimum environment for nerve
      regeneration.

PMID- 24043117
TI  - A unique case of dendritic cell neoplasm from monocyte-derived myeloid origin
      with distinct immunophenotype and cytomorphology.

PMID- 24043118
TI  - Master regulators of FGFR2 signalling and breast cancer risk.
AB  - The fibroblast growth factor receptor 2 (FGFR2) locus has been consistently
      identified as a breast cancer risk locus in independent genome-wide association
      studies. However, the molecular mechanisms underlying FGFR2-mediated risk are
      still unknown. Using model systems we show that FGFR2-regulated genes are
      preferentially linked to breast cancer risk loci in expression quantitative trait
      loci analysis, supporting the concept that risk genes cluster in pathways. Using
      a network derived from 2,000 transcriptional profiles we identify SPDEF, ERalpha,
      FOXA1, GATA3 and PTTG1 as master regulators of fibroblast growth factor receptor
      2 signalling, and show that ERalpha occupancy responds to fibroblast growth
      factor receptor 2 signalling. Our results indicate that ERalpha, FOXA1 and GATA3
      contribute to the regulation of breast cancer susceptibility genes, which is
      consistent with the effects of anti-oestrogen treatment in breast cancer
      prevention, and suggest that fibroblast growth factor receptor 2 signalling has
      an important role in mediating breast cancer risk. 

PMID- 24043119
TI  - Authors' reply: Proper surgical training and grading of complications for Shang
      Ring circumcision are necessary.

PMID- 24043120
TI  - Author's reply: A randomized trial of Mogen clamp versus Plastibell for neonatal
      male circumcision in Botswana.

PMID- 24043121
TI  - Novel biosensing methodologies for ultrasensitive detection of viruses.
AB  - Various infectious diseases caused by the spread of viruses create adverse
      implications on global biosecurity. Increasing demands for virus surveillance and
      effective control of the spread of diseases reveal the need for rapid and
      sensitive virus diagnostic devices. Due to the remarkable sensitivity and
      specificity of biosensors, they appear as a potential and promising tool for
      accurate and quantitative detection of viruses. Furthermore, recent advancements
      in transduction systems, nanotechnology and genetic engineering offer various
      strategies to improve the detection performance of biosensors. This review
      presents an overview of the current states of novel biosensing methodologies for
      the ultrasensitive detection of viruses with highly promising applications for
      future disease diagnosis. Additionally, a brief summary of the recent state-of
      the-art virus diagnostic molecular technologies is included. 

PMID- 24043122
TI  - Memory-enhancing effects of silk fibroin-derived peptides in scopolamine-treated
      mice.
AB  - Although enzyme-hydrolyzed silk fibroin has been reported to enhance cognitive
      function before, it has been still unknown which peptides can improve memory.
      Here we report that amino acid sequences of three novel peptides were identified
      from fibroin hydrolysate. Fibroin hydrolysate was obtained by hydrolysis with
      protease after partial hydrolysis with 5M CaCl2. Synthesized peptides derived
      from these sequences improved scopolamine-induced memory impairments in mice. We
      confirmed this hydrolysate had effects that improved learning and memory
      abilities by performing the Rey-Kim test. From this hydrolysate of silk fibroin,
      amino acid sequences of eight peptides were identified by LC-MS/MS. Three
      peptides (GAGAGTGSSGFGPY, GAGAGSGAGSGAGAGSGAGAGY, and SGAGSGAGAGSGAGAGSGA) were
      synthesized to investigate whether they could improve memory. Passive avoidance
      test and Morris water maze test were performed, and all peptides showed memory
      enhancing abilities on scopolamine-induced memory impairments in mice. In this
      study, we identified three novel peptides that could improve memory, and that
      silk fibroin hydrolysate was a mixture of various active peptides that could
      enhance memory. 

PMID- 24043123
TI  - Development of indole-3-acetic acid-producing Escherichia coli by functional
      expression of IpdC, AspC, and Iad1.
AB  - Biosynthesis of indole-3-acetic acid (IAA) via the indole-3-pyruvic acid pathway
      involves three kinds of enzymes; aminotransferase encoded by aspC, indole-3
      pyruvic acid decarboxylase encoded by ipdC, and indole-3-acetic acid
      dehydrogenase encoded by iad1. The ipdC from Enterobacter cloacae ATCC 13047,
      aspC from Escherichia coli, and iad1 from Ustilago maydis were cloned and
      expressed under the control of the tac and sod promoters in E. coli. According to
      SDS-PAGE and enzyme activity, IpdC and Iad1 showed good expression under the
      control of P(tac), whereas AspC was efficiently expressed by P(sod) originating
      from Corynebacterium glutamicum. The activities of IpdC, AspC, and Iad1 from the
      crude extracts of recombinant E. coli Top 10 were 215.6, 5.7, and 272.1
      nmol/min/mg-protein, respectively. The recombinant E. coli DH5alpha expressing
      IpdC, AspC, and Iad1 produced about 1.1 g/l of IAA and 0.13 g/l of tryptophol
      (TOL) after 48 h of cultivation in LB medium with 2 g/l tryptophan. To improve
      IAA production, a tnaA gene mediating indole formation from tryptophan was
      deleted. As a result, E. coli IAA68 with expression of the three genes produced
      1.8 g/l of IAA, which is a 1.6- fold increase compared with wild-type DH5alpha
      harboring the same plasmids. Moreover, the complete conversion of tryptophan to
      IAA was achieved by E. coli IAA68. Finally, E. coli IAA68 produced 3.0 g/l of IAA
      after 24 h cultivation in LB medium supplemented with 4 g/l of tryptophan.

PMID- 24043124
TI  - Media optimization for laccase production by Trichoderma harzianum ZF-2 using
      response surface methodology.
AB  - Trichoderma harzianum ZF-2 producing laccase was isolated from decaying samples
      from Shandong, China, and showed dye decolorization activities. The objective of
      this study was to optimize its culture conditions using a statistical analysis of
      its laccase production. The interactions between different fermentation
      parameters for laccase production were characterized using a Plackett-Burman
      design and the response surface methodology. The different media components were
      initially optimized using the conventional one-factor-at-a-time method and an
      orthogonal test design, and a Plackett-Burman experiment was then performed to
      evaluate the effects on laccase production. Wheat straw powder, soybean meal, and
      CuSO4 were all found to have a significant influence on laccase production, and
      the optimal concentrations of these three factors were then sequentially
      investigated using the response surface methodology with a central composite
      design. The resulting optimal medium components for laccase production were
      determined as follows: wheat straw powder 7.63 g/l, soybean meal 23.07 g/l,
      (NH4)2SO4 1 g/l, CuSO4 0.51 g/l, Tween-20 1 g/l, MgSO4 1 g/l, and KH2PO4 0.6 g/l.
      Using this optimized fermentation method, the yield of laccase was increased
      59.68 times to 67.258 U/ml compared with the laccase production with an
      unoptimized medium. This is the first report on the statistical optimization of
      laccase production by Trichoderma harzianum ZF-2.

PMID- 24043125
TI  - Fungal diversity of rice straw for meju fermentation.
AB  - Rice straw is closely associated with meju fermentation and it is generally known
      that the rice straw provides meju with many kinds of microorganisms. In order to
      elucidate the origin of meju fungi, the fungal diversity of rice straw was
      examined. Rice straw was collected from 12 Jang factories where meju are
      produced, and were incubated under nine different conditions by altering the
      media (MEA, DRBC, and DG18), and temperature (15 degrees C, 25 degrees C, and 35
      degrees C). In total, 937 strains were isolated and identified as belonging to 39
      genera and 103 species. Among these, Aspergillus, Cladosporium, Eurotium,
      Fusarium, and Penicillium were the dominant genera. Fusarium asiaticum (56.3%),
      Cladosporium cladosporioides (48.6%), Aspergillus tubingensis (37.5%), A. oryzae
      (31.9%), Eurotium repens (27.1%), and E. chevalieri (25.0%) were frequently
      isolated from the rice straw obtained from many factories. Twelve genera and 40
      species of fungi that were isolated in the rice straw in this study were also
      isolated from meju. Specifically, A. oryzae, C. cladosporioides, E. chevalieri,
      E. repens, F. asiaticum, and Penicillium polonicum (11.8%), which are abundant
      species in meju, were also isolated frequently from rice straw. C.
      cladosporioides, F. asiaticum, and P. polonicum, which are abundant in the low
      temperature fermentation process of meju fermentation, were frequently isolated
      from rice straw incubated at 15 degrees C and 25 degrees C, whereas A. oryzae, E.
      repens, and E. chevalieri, which are abundant in the high temperature
      fermentation process of meju fermentation, were frequently isolated from rice
      straw incubated at 25 degrees C and 35 degrees C. This suggests that the
      mycobiota of rice straw has a large influence in the mycobiota of meju. The
      influence of fungi on the rice straw as feed and silage for livestock, and as
      plant pathogens for rice, are discussed as well. 

PMID- 24043126
TI  - Emergence of GII.4 Sydney norovirus in South Korea during the winter of 2012
      2013.
AB  - Norovirus is the major cause of acute gastroenteritis worldwide. Between November
      2012 and June 2013, 1718 stool samples were requested for norovirus antigen
      testing in the metropolitan areas of South Korea, and 91 samples were genotyped.
      The norovirus antigen-positive rate peaked at 52.8% in December 2012.
      [corrected]. A novel norovirus GII.4 variant, GII.4 Sydney 2012, was the most
      frequently found genotype (60.4%) during this period. This study demonstrates
      that norovirus activity increased during the winter of 2012-2013 in South Korea
      and that norovirus GII.4 Sydney 2012 was the cause of the norovirus epidemic
      during this period.

PMID- 24043127
TI  - Continuity of care and the risk of preventable hospitalization in older adults.
AB  - IMPORTANCE: Preventable hospitalizations are common among older adults for
      reasons that are not well understood. OBJECTIVE: To determine whether Medicare
      patients with ambulatory visit patterns indicating higher continuity of care have
      a lower risk of preventable hospitalization. DESIGN: Retrospective cohort study.
      SETTING: Ambulatory visits and hospital admissions. PARTICIPANTS: Continuously
      enrolled fee-for-service Medicare beneficiaries older than 65 years with at least
      4 ambulatory visits in 2008. EXPOSURES: The concentration of patient visits with
      physicians measured for up to 24 months using the continuity of care score and
      usual provider continuity score on a scale from 0 to 1. MAIN OUTCOMES AND
      MEASURES: Index occurrence of any 1 of 13 preventable hospital admissions,
      censoring patients at the end of their 24-month follow-up period if no
      preventable hospital admissions occurred, or if they died. RESULTS: Of the
      3,276,635 eligible patients, 12.6% had a preventable hospitalization during their
      2-year observation period, most commonly for congestive heart failure (25%),
      bacterial pneumonia (22.7%), urinary infection (14.9%), or chronic obstructive
      pulmonary disease (12.5%). After adjustment for patient baseline characteristics
      and market-level factors, a 0.1 increase in continuity of care according to
      either continuity metric was associated with about a 2% lower rate of preventable
      hospitalization (continuity of care score hazard ratio [HR], 0.98 [95% CI, 0.98
      0.99; usual provider continuity score HR, 0.98 [95% CI, 0.98-0.98). Continuity of
      care was not related to mortality rates. CONCLUSIONS AND RELEVANCE: Among fee-for
      service Medicare beneficiaries older than 65 years, higher continuity of
      ambulatory care is associated with a lower rate of preventable hospitalization.

PMID- 24043128
TI  - A cohort study comparing a single-incision sling with a retropubic midurethral
      sling.
AB  - INTRODUCTION AND HYPOTHESIS: Despite established comparable efficacy between
      retropubic midurethral (RMUS) and transobturator slings, there are conflicting
      data regarding single-incision mini-slings (SIMS). This study tests the null
      hypothesis that the MiniArc(r) Single-Incision Sling is equivalent to the
      ALIGN(r) Urethral Support System for treatment of stress urinary incontinence
      (SUI). METHODS: Women who underwent a sling for SUI from 1 January 2008 through
      31 December 2009 were identified (N = 324). A follow-up survey was mailed.
      Primary outcomes were treatment failure, defined as International Consultation on
      Incontinence Questionnaire (ICIQ) score >0 or additional anti-incontinence
      procedure, and stress-specific incontinence (SSI). Secondary outcomes included
      Patient Global Impression of Severity and Improvement (PGI-SI), satisfaction, de
      novo urge, and complications. RESULTS: The study included 202 women who returned
      the survey. The SIMS group had higher body mass index (BMI) (30.7 +/- 6.5 vs 28.9
      +/- 6.0 kg/m(2), P = 0.052) and shorter follow-up (18.6 +/- 11.5 vs 22.9 +/- 14.6
      months, P = 0.019). Treatment failure was higher in SIMS compared with RMUS (76.3
      % vs 64.2 %) with adjusted odds ratio of 1.84 (95 % CI, 1.0, 3.5). The SIMS group
      was more likely to have postoperative SSI, with adjusted OR of 2.4 (95 % CI; 1.3
      4.5). The RMUS group reported more improvement and satisfaction. Incidence of de
      novo urge and complications were similar between groups. Reoperation for mesh
      erosion was more likely in the RMUS group, while the SIMS had a higher
      reoperation rate for SUI. CONCLUSIONS: Compared with retropubic ALIGN(r) Slings,
      MiniArc(r) Single-Incision Slings are less effective, with more postoperative
      incontinence, less patient-reported improvement, satisfaction, and higher
      reoperation rates for SUI.

PMID- 24043130
TI  - Work behaviour during pregnancy in rural China in 2009.
AB  - OBJECTIVES: To describe the pattern and determinants of working during pregnancy
      in rural China. METHODS: A cross-sectional survey was carried out in 2009 in
      three provinces (Anhui, Chongqing and Shaanxi) in rural China among 3966 mothers
      who had recently given birth. Multilevel logistic regression was used to examine
      the determinants of work behaviour during pregnancy. RESULTS: Overall, 39% of the
      women stopped working during early pregnancy, 32% worked the same throughout
      pregnancy and the rest decreased their work or stopped later in pregnancy. Women
      from Anhui (53%) and Chongqing (54%) provinces were more likely to stop work in
      early pregnancy than women from Shaanxi province (20%). Older women [odds ratio
      (OR) 0.74, 95% confidence interval (CI) 0.56-0.99], those having two or more
      children (OR 0.55, 95% CI 0.43-0.69) and non-farmers (OR 0.50, 95% CI 0.65-0.99)
      were less likely to stop working on the first trimester, but those with higher
      education (high school OR 1.43, 95% CI 1.05-1.94) were more likely to stop
      working. Stopping work early was not related to household income and adequacy of
      prenatal care. Women with two or more children, non-farmers and those from
      Shaanxi province were more likely to continue to work to the same extent during
      pregnancy. But those with higher household income and middle and high school were
      less likely to work the same. CONCLUSIONS: Women's working patterns during
      pregnancy in rural China were polarized: many women stopped working already in
      early pregnancy, but others continued to work as before. The key determinant of
      the working patterns was the province of residence.

PMID- 24043129
TI  - Urethral striated muscle and extracellular matrix morphological characteristics
      among mildly diabetic pregnant rats: translational approach.
AB  - INTRODUCTION AND HYPOTHESIS: Diabetes mellitus (DM) during pregnancy is
      associated with high levels of urinary incontinence (UI) and pelvic floor muscle
      dysfunction. Mild DM can lead to changes in urethral striated muscle and
      extracellular matrix (ECM) in pregnant rats considering both structures as an
      entire system responsible for urinary continence. METHODS: Ninety-two female
      Wistar rats were distributed in four experimental groups: virgin, pregnant,
      diabetic, and diabetic pregnant. In adult life, parental nondiabetic female rats
      were mated with nondiabetic male rats to obtain newborns. At the first day of
      birth, newborns received citrate buffer (nondiabetic group) or streptozotocin 100
      mg/kg body weight, subcutaneous route (mild DM group). At day 21 of the
      pregnancy, the rats were lethally anesthetized and the urethra and vagina were
      extracted as a unit. Urethral and vaginal sections were cut and analyzed by: (a)
      cytochemical staining for ECM and muscle structural components, (b)
      immunohistochemistry to identify fast- and slow-muscle fibers, and (c)
      transmission electron microscopy for ultrastructural analysis of urethral
      striated muscle. RESULTS: In comparison with the three control groups, variations
      in the urethral striated muscle and ECM from diabetic pregnant rats were observed
      including thinning, atrophy, fibrosis, increased area of blood vessels,
      mitochondria accumulation, increased lipid droplets, glycogen granules associated
      with colocalization of fast and slow fibers, and a steady decrease in the
      proportion of fast to slow fibers. CONCLUSIONS: Mild DM and pregnancy can lead to
      a time-dependent disorder and tissue remodeling in which the urethral striated
      muscle and ECM has a fundamental function.

PMID- 24043131
TI  - The disease burden across different ethnic groups in Amsterdam, the Netherlands,
      2011-2030.
AB  - BACKGROUND: Current disease burden estimates do not provide evidence across
      different ethnic groups. This study aims to assess the disease burden as measured
      by the disability-adjusted life years (DALYs) for six ethnic groups in Amsterdam,
      the Netherlands, for 2011 and 2030. METHODS: The DALYs were calculated by
      combining three components: disease-/sex-/age-specific DALYs per person; disease
      specific relative risks (RRs) by ethnicity; and sex-/age-specific population
      sizes by ethnicity in Amsterdam in 2011 and 2030. Disease-specific DALYs were
      derived from the National Institute of Public Health. The RRs were obtained
      through a systematic review of studies published in 1997-2008. The population
      figures were gathered from the Statistics Netherlands and municipality of
      Amsterdam. RESULTS: The findings suggest that cardiovascular diseases and anxiety
      and depressive disorders dominate disease burden in all ethnic groups in 2011 and
      2030. In most of the non-Western ethnic minorities, diabetes mellitus is the
      strongest contributor to the disease burden. The total disease burden will
      increase more strongly in non-Western ethnic minorities than ethnic Dutch. The
      2030 disease burden is estimated to be highest among Surinamese and Antilleans.
      CONCLUSIONS: In ethnic minorities, diabetes plays an important role in the
      disease burden, and the total disease burden will grow stronger than ethnic
      Dutch, resulting in a higher total disease burden for some ethnic groups in 2030.
      We encourage researchers to estimate the disease burden by ethnicity so that
      health priorities can be set in the fields of policy, health care and research.

PMID- 24043132
TI  - SuperNova, a monomeric photosensitizing fluorescent protein for chromophore
      assisted light inactivation.
AB  - Chromophore-assisted light inactivation (CALI) is a powerful technique for acute
      perturbation of biomolecules in a spatio-temporally defined manner in living
      specimen with reactive oxygen species (ROS). Whereas a chemical photosensitizer
      including fluorescein must be added to specimens exogenously and cannot be
      restricted to particular cells or sub-cellular compartments, a genetically
      encoded photosensitizer, KillerRed, can be controlled in its expression by tissue
      specific promoters or subcellular localization tags. Despite of this superiority,
      KillerRed hasn't yet become a versatile tool because its dimerization tendency
      prevents fusion with proteins of interest. Here, we report the development of
      monomeric variant of KillerRed (SuperNova) by direct evolution using random
      mutagenesis. In contrast to KillerRed, SuperNova in fusion with target proteins
      shows proper localization. Furthermore, unlike KillerRed, SuperNova expression
      alone doesn't perturb mitotic cell division. Supernova retains the ability to
      generate ROS, and hence promote CALI-based functional analysis of target proteins
      overcoming the major drawbacks of KillerRed. 

PMID- 24043133
TI  - Knockdown of mTOR by lentivirus-mediated RNA interference suppresses
      atherosclerosis and stabilizes plaques via a decrease of macrophages by autophagy
      in apolipoprotein E-deficient mice.
AB  - Atherosclerotic plaque destabilization and rupture leads to acute coronary
      syndromes which cause serious damage to human health worldwide. However, there is
      currently a lack of efficient therapeutic methods. Mammalian target of rapamycin
      (mTOR) has been suggested to be involved in the development of atherosclerotic
      plaques and serves as a therapeutic target. The present study was performed to
      determine whether RNA interference (RNAi) of mTOR in vivo by LV-mediated small
      hairpin RNA (shRNA) was capable of inhibiting the progression of atherosclerotic
      plaques. LV-mediated shRNA against mTOR (LV-shmTOR) was designed and obtained.
      Male apolipoprotein E-deficient mice were fed a high-fat diet and a constrictive
      collar was placed around the right carotid arteries of these mice to induce
      plaque formation. Eight weeks after surgery, mice were randomly divided into the
      mTOR RNA interference (LV-shmTOR) group, receiving treatment with LV-mTOR-shRNA;
      the LV-shCON group, receiving treatment with LV-non-specific-shRNA; and the
      control group, receiving treatment with phosphate-buffered saline. Following
      transfection, the mice were sacrificed to evaluate the effects of mTOR expression
      silencing on atherosclerosis. Transfection of LV-mTOR-shRNA markedly inhibited
      the mRNA and protein expression levels. Knockdown of mTOR ameliorated
      dysregulated blood lipid metabolism and stabilized aortic atherosclerotic plaques
      by decreasing the plaque area and increasing the fibrous cap and cap-to-core
      ratio. Furthermore, macrophages were decreased by silencing mTOR in
      atherosclerotic plaques. In addition, western blot analysis revealed that the
      knockdown of mTOR increased autophagy-related protein 13 (Atg13)
      dephosphorylation and light chain 3-I/light chain 3-II (LC3-I/LC3-II) ratios,
      both of which were associated with a high activity of autophagy, suggesting an
      increase of autophagy in atherosclerotic plaques. Moreover, genes including
      matrix metalloproteinase 2, monocyte chemoattractant protein 1 and tissue factor,
      which promote plaque instability, were downregulated by silencing mTOR. These
      results demonstrate that LV-mediated mTOR silencing by RNAi treatment induces
      macrophage autophagy and is a potential strategy for the treatment of
      atherosclerotic plaques.

PMID- 24043134
TI  - Spiral resonators for on-chip laser frequency stabilization.
AB  - Frequency references are indispensable to radio, microwave and time keeping
      systems, with far reaching applications in navigation, communication, remote
      sensing and basic science. Over the past decade, there has been an optical
      revolution in time keeping and microwave generation that promises to ultimately
      impact all of these areas. Indeed, the most precise clocks and lowest noise
      microwave signals are now based on a laser with short-term stability derived from
      a reference cavity. In spite of the tremendous progress, these systems remain
      essentially laboratory devices and there is interest in their miniaturization,
      even towards on-chip systems. Here we describe a chip-based optical reference
      cavity that uses spatial averaging of thermorefractive noise to enhance resonator
      stability. Stabilized fibre lasers exhibit relative Allan deviation of 3.9 * 10
      13 at 400 MUs averaging time and an effective linewidth <100 Hz by achieving over
      26 dB of phase-noise reduction.

PMID- 24043135
TI  - The spectroscopic ruler revisited at 77 K.
AB  - We report on single-molecule FRET measurements on the classical molecular ruler
      polyproline immersed in amorphous ice at 77 K. Confocal scanning microscopy
      allows for observation of the fluorescence of the dyes Alexa Fluor 488 as the
      donor and Alexa Fluor 594 as the acceptor in the FRET experiment. The dipole
      orientations are fixed in amorphous ice leading to a broad distribution of
      transfer efficiencies. The measured transfer efficiency distributions are mainly
      in accordance with simulated distributions, with a significant deviation at low
      transfer efficiencies, which are absent in the experimental distribution, in
      stark contrast to the theory. 

PMID- 24043136
TI  - DCA increases the antitumor effects of capecitabine in a mouse B16 melanoma
      allograft and a human non-small cell lung cancer A549 xenograft.
AB  - PURPOSE: Capecitabine is one of the few chemotherapy drugs with high oral
      availability. Recently, sodium dichloroacetate (DCA) has shown great potential as
      an anticancer agent. In the present study, we assessed the anticancer effect of
      DCA in combination with capecitabine for cancers that modestly expressed TP.
      METHODS: A mouse B16 melanoma allograft and a human non-small cell lung cancer
      A549 xenograft were used to assess the effect of DCA and capecitabine combined
      treatment. Histology and immunohistochemistry were used to detect the apoptosis
      and proliferation of cancer cells. Real-time PCR and Western blot were carried
      out to detect the expression of TP and caspases, respectively. RESULTS: For the
      first time, we report that DCA increased the antitumor effects of capecitabine in
      a mouse B16 allograft and a human A549 xenograft by promoting apoptosis of tumor
      cells. DCA has little effect on the expression of TP. CONCLUSIONS: Our finding
      suggests that DCA in combination with capecitabine might be potential as a new
      therapeutic regimen against some cancers.

PMID- 24043137
TI  - Phase I study of the safety, pharmacokinetics and antitumor activity of
      famitinib.
AB  - PURPOSE: To evaluate the safety, tolerability, pharmacokinetics and antitumor
      activities of famitinib (famitinib L-malate), a novel oral multitargeting
      tyrosine kinase inhibitor that acts against vascular endothelial growth factor
      receptor-2, platelet-derived growth factor receptor, stem cell factor receptor (c
      kit), FMS-like tyrosine kinase-3 receptor and protooncogene tyrosine kinase
      receptor in patients with advanced solid cancer. METHODS: Patients received once
      daily oral famitinib. Doses were increased from 4 to 8, 13, 20, 27, 24, 25 and
      eventually 30 mg. Each cycle was defined as 28 days. The pharmacokinetic profile
      and various biomarkers were evaluated during the first cycle. Antitumor efficacy
      was evaluated every 8 weeks. RESULTS: Fifty-four patients were evaluable for
      safety and efficacy. Dose-limiting toxicities were observed in 2 of 3 patients at
      30 mg. The dose-limiting toxicities observed in the first cycle of famitinib
      treatment included hypertension, hand-foot skin reaction and diarrhea. Grade 3
      hypertriglyceridemia/hypercholesterolemia and proteinuria were notable side
      effects in the subsequent treatment cycles. Other common side effects included
      bone marrow suppression, oral mucositis, fatigue, pain, elevated transaminase or
      bilirubin, peripheral sensory disturbance and hypothyroidism, most of which were
      mild to moderate in severity. Pharmacokinetic studies revealed no significant
      accumulation of famitinib or its major metabolite, M3. The half-lives of
      famitinib and M3 were approximately 28.7-33.8 and 41.3-47.7 h, respectively. Food
      demonstrated a minimal effect on the pharmacokinetics of famitinib. Eight partial
      responses were determined, including 6 cases of renal cell carcinoma, 1 case of
      gastrointestinal stromal tumor (GIST) and 1 case of alveolar soft part sarcoma.
      Fourteen patients demonstrated stable disease with various degrees of tumor
      shrinkage. CONCLUSIONS: Famitinib is generally well tolerated. Famitinib
      demonstrates a wide spectrum of antitumor activities, which warrants further
      study in renal cell carcinoma, GIST, hepatocellular carcinoma and soft tissue
      sarcoma. The recommended dose for future phase II clinical trials is 25 mg.

PMID- 24043138
TI  - Changes in fPSA level could discriminate tPSA flare-up from tPSA progression in
      patients with castration-refractory prostate cancer during the initial phase of
      docetaxel-based chemotherapy.
AB  - PURPOSE: To evaluate whether changes in fPSA level could predict tPSA flare-up in
      patients with castration-refractory prostate cancer during the initial phase of
      docetaxel-based chemotherapy. METHODS: We retrospectively identified 79
      consecutive patients who received docetaxel-based chemotherapy at our
      institution. The treatment protocols included docetaxel 75 mg/m2 every 21 days,
      with either prednisone 5 mg twice daily or estramustine 280 mg three times daily
      on days 1-5; treatment with dexamethasone preceded docetaxel therapy. All PSA
      values were determined before every cycle of docetaxel-based treatment. RESULTS:
      According to changes in tPSA level, 79 patients were divided into 3 groups:
      response (group 1), progression (group 2) and flare-up (group 3). fPSA and tPSA
      levels showed different patterns in groups 1, 2 and 3. Changes in fPSA level were
      independent of the changes in tPSA level in group 3, which decreased during
      chemotherapy. However, comparing with fPSA changes in group 3, changes in fPSA
      level were in accordance with tPSA changes in groups 1 and 2. Estimated median
      survival in groups 1, 2 and 3 was 23, 13 and 21 months, respectively. Median
      survival for patients in groups 1 (P = 0.008 vs group 2) and 3 (P = 0.029 vs
      group 2) is significantly longer than for patients who experienced progressive
      disease under therapy. However, there was no statistically significant difference
      in survival between groups 1 and 3. CONCLUSIONS: In the present study, we
      observed that changes in fPSA level could possibly discriminate tPSA flare-up
      from tPSA progression in patients with castration-refractory prostate cancer
      during the initial phase of docetaxel-based chemotherapy.

PMID- 24043139
TI  - Oxetane synthesis through the Paterno-Buchi reaction.
AB  - The Paterno-Buchi reaction is a photochemical reaction between a carbonyl
      compound and an alkene to give the corresponding oxetane. In this review the
      mechanism of the reaction is discussed. On this basis the described use in the
      reaction with electron rich alkenes (enolethers, enol esters, enol silyl ethers,
      enanines, heterocyclic compounds has been reported. The stereochemical behavior
      of the reaction is particularly stressed. We pointed out the reported
      applications of this reaction to the synthesis of naturally occuring compounds. 

PMID- 24043140
TI  - Harvestman phenols and benzoquinones: characterisation and biosynthetic pathway.
AB  - Benzoquinones are usually present in arthropod defence exudates. Here, we
      describe the chemical profiles of 12 harvestman species belonging to the
      neotropical family Gonyleptidae. Nine of the studied species produced
      benzoquinones, while three produced alkyl phenols. Two benzoquinones and one
      phenol exhibited biological activity against bacteria and fungi. We also studied
      the biosynthesis of 2-ethyl-1,4-benzoquinone by feeding Magnispina neptunus
      individuals with 13C-labelled precursors; the benzoquinones were biosynthesised
      through a polyketide pathway using acetate and propionate building blocks.

PMID- 24043141
TI  - Determination and pharmacokinetics of di-(2-ethylhexyl) phthalate in rats by
      ultra performance liquid chromatography with tandem mass spectrometry.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is used to increase the flexibility of
      plastics for industrial products. However, the illegal use of the plasticizer
      DEHP in food and drinks has been reported in Taiwan in 2011. In order to assess
      the exact extent of the absorption of DEHP via the oral route, the aim of this
      study is to develop a reliable and validated ultra performance liquid
      chromatography with tandem mass spectrometry (UPLC-MS/MS) method to evaluate the
      oral bioavailability of DEHP in rats. The optimal chromatographic separation of
      DEHP and butyl benzyl phthalate (BBP; used as internal standard) were achieved on
      a C18 column. The mobile phase was consisted of 5 mM ammonium acetate-methanol
      (11:89, v/v) with a flow rate of 0.25 mL/min. The monitoring ion transitions were
      m/z 391.4 -> 149.0 for DEHP and m/z 313.3 -> 149.0 for BBP. The mean matrix
      effects of DEHP at low, medium and high concentrations were 94.5 +/- 5.7% and
      100.1 +/- 2.3% in plasma and feces homogenate samples, respectively. In
      conclusion, the validated UPLC-MS/MS method is suitable for analyzing the rat
      plasma sample of DEHP and the oral bioavailability of DEHP was about 7% in rats.

PMID- 24043142
TI  - Probing the residual structure in avian prion hexarepeats by CD, NMR and MD
      techniques.
AB  - Many proteins perform essential biological functions by means of regions that
      lacking specific organized structure exist as an ensemble of interconverting
      transient conformers. The characterization of such regions, including the
      description of their structural propensities, number of conformations and
      relative populations can provide useful insights. Prion diseases result from the
      conversion of a normal glycoprotein into a misfolded pathogenic isoform. The
      structures of mammal and chicken prion proteins show a similar fold with a
      globular domain and a flexible N-terminal portion that contains different
      repeated regions: octarepeats (PHGGGWGQ) in mammals and hexarepeats (PHNPGY) in
      chickens. The higher number of prolines in the hexarepeat region suggests that
      this region may retain a significant amount of residual secondary structure.
      Here, we report the CD, NMR and MD characterization of a peptide (2-HexaPY)
      composed of two hexarepeats. We combine experimental NMR data and MD to
      investigate at atomic level its ensemble-averaged structural properties,
      demonstrating how each residue of both repeats has a different quantified PPII
      propensity that shows a periodicity along the sequence. This feature explains the
      absence of cooperativity to stabilize a PPII conformation. Nonetheless, such
      residual structure can play a role in nucleating local structural transitions as
      well as modulating intra-molecular or inter-molecular interactions. 

PMID- 24043143
TI  - Fremy's salt-mediated oxidative addition. A new approach in the total synthesis
      of naturally dipetalolactone and its immunomodulatory activity.
AB  - The structure of the natural dipyranocoumarin dipetalolactone has been confirmed
      by an unambiguous synthetic route from resorcinol. This sequence was initiated by
      a pyran ring formation step which introduced the 3-chloro-3-methylbut-1-yne
      moiety. Then, the expected product undergoes a Fremy's salt-meditated oxidative
      addition followed by ring closure to yield dipetalolactone. Dipetalolactone was
      also found to have immunological activity in a mouse carcinoma S180-bearing mice
      cell line. 

PMID- 24043144
TI  - Tissue valve is the preferred option for patients aged 60 and older.

PMID- 24043145
TI  - Selection of aortic valve prostheses: contemporary reappraisal of mechanical
      versus biologic valve substitutes.

PMID- 24043146
TI  - Arrhythmogenic right ventricular cardiomyopathy: a challenging disease of the
      intercalated disc.

PMID- 24043147
TI  - ECG Response: September 17, 2013.

PMID- 24043148
TI  - Multiple myocardial clefts on cardiac magnetic resonance imaging.

PMID- 24043149
TI  - Iatrogenic aortopulmonary window and pulmonary artery dissection secondary to
      aortic cannulation.

PMID- 24043151
TI  - Letter by Dillinger et al regarding article, "Drug resistance and
      pseudoresistance: an unintended consequence of enteric coating aspirin".

PMID- 24043152
TI  - Letter by Wallace and Chan regarding article, "Drug resistance and
      pseudoresistance: an unintended consequence of enteric coating aspirin".

PMID- 24043153
TI  - Response to letters regarding article, "Drug resistance and pseudoresistance: an
      unintended consequence of enteric coating aspirin".

PMID- 24043156
TI  - Water adsorption and dissociation on Ni surface: effects of steps, dopants,
      coverage and self-aggregation.
AB  - Water-metal interaction has been receiving extensive attention due to its
      interdisciplinary application. In this paper, on the basis of first-principle
      calculations and slab models, the behavior of water adsorption and dissociation
      on planar, stepped and blocked Ni surfaces is investigated, the effects of steps,
      Au and Ag dopants, coverage and self-aggregation of water are also disclosed. The
      results show that: step not only strengthens water-substrate interaction but also
      facilitates water dissociation. With dopants modification, the adsorption and
      dissociation properties remain relatively unchanged at lower coverage (1/9 on
      facets and 1/12 ML on steps) while at higher coverage (1/4 on facets and 1/6 ML
      on steps) water adsorption is weakened and dissociation activity decreases
      dramatically. Water adsorption and dissociation properties on Ni surfaces are
      essentially unaffected with the increase of coverage. On doped surfaces,
      adsorption properties and dissociation activities are closely associated with the
      ligand effect, which is dependent on the dopant, dopant concentration and surface
      morphology. Water self-aggregation enhances water-surface interaction on all
      studied surfaces due to hydrogen bond (network) formation. Furthermore,
      investigation shows that it does not assist water dissociation. 

PMID- 24043157
TI  - A New 4 DOF Parallel Kinematic Structure for use in a Single Port Robotic
      Instrument with Haptic Feedback.

PMID- 24043155
TI  - Inflammation and coagulation in atherosclerosis.
AB  - Cardiovascular diseases remain to be the leading cause of death in Western
      societies. Despite major findings in vascular biology that lead to a better
      understanding of the pathomechanisms involved in atherosclerosis, treatment of
      the disease has only changed slightly within the last years. A big body of
      evidence suggests that atherosclerosis is a chronic inflammatory disease of the
      vessel wall. Accumulation and peroxidation of LDL-particles within the vessel
      wall trigger a strong inflammatory response, causing macrophage and T-cell
      accumulation within the vessel wall. Additionally, B-cells and specific
      antibodies against LDL-particles, as well as the complement system are implicated
      in atherogenesis. Besides data from clinical trials and autopsy studies it was
      the implementation of mouse models of atherosclerosis and the emerging field of
      direct gen-modification that lead to a thorough description of the
      pathophysiological mechanisms involved in the disease and created overwhelming
      evidence for a participation of the immune system. Recently, the cross-talk
      between coagulation and inflammation in atherogenesis has gained attention.
      Serious limitations and disparities in the pathophysiology of atherosclerosis in
      mice and men complicated the translation of experimental data into clinical
      practice. Despite these limitations, new anti-inflammatory medical therapies in
      cardiovascular disease are currently being tested in clinical trials. 

PMID- 24043158
TI  - The Future of Notes (Natural Orifice Translumenal Endoscopic Surgery) Technology.

PMID- 24043159
TI  - Shape Memory Microactuator for Surgical Instruments.

PMID- 24043160
TI  - New Device for Ergonomic Control of a Surgical Robot with 4 DOF Including Haptic
      Feedback.

PMID- 24043161
TI  - E-Learning as Integral Part of Teaching-Learning Processes in Continuing
      Education for Ambient Assisted Living Technologies and Services.

PMID- 24043162
TI  - Pacemaker and Defibrillator Teaching System with Carelink and Homemonitoring
      Remote Patient Monitoring.

PMID- 24043163
TI  - E-learning in engineering studies - experience of the Ilmenau University of
      Technology.

PMID- 24043164
TI  - Medical device introduction to medical personnel by using simulated scenarios in
      modern simulation centres.

PMID- 24043165
TI  - How Problem Based Learning can Facilitate Training on Hard and Soft Skills.

PMID- 24043166
TI  - Physico-Technical Medicine - Teaching Technical Skills to the Physician.

PMID- 24043167
TI  - Involving Industry in Medical Engineering Education.

PMID- 24043168
TI  - Experiences with Online Courses for Regulatory Affairs - Modules for Continuing
      Education and Master Programmes as well.

PMID- 24043169
TI  - Technological competence for surgeons - results of an international study.

PMID- 24043170
TI  - Combining Real World Problems with Student Competitions in Engineering Education.

PMID- 24043171
TI  - Benefits of Blended Learning in Biomedical Engineering.

PMID- 24043172
TI  - Artificial Vertebrae for a Novel Simulator in Minimally Invasive Spine Surgery.

PMID- 24043173
TI  - Breath Analysis Using Ion Mobility Spectrometry (Ims) As Diagnostic Tool In
      Equine Reproduction Medicine.

PMID- 24043174
TI  - On the Development of a Test Setup for a Non-Destructive Quality Control of
      Centifluidic Medical Devices.

PMID- 24043175
TI  - A tactile P300-based BCI for communication and detection of awareness.

PMID- 24043176
TI  - Investigation of noise levels in intensive care units.

PMID- 24043177
TI  - Rapid Pacing Induces Fractionation of the Activation Wavefront into Multiple
      Wavelets.

PMID- 24043178
TI  - Skin impedance measurements support ex-vivo penetration studies for topical
      applied drugs.

PMID- 24043179
TI  - Brain-Actuated Assistive Mobility for Disabled End-User.

PMID- 24043180
TI  - Time-Domain Correlations of Imagined Arm Positions with Brain Sources.

PMID- 24043181
TI  - Ultrasound Sensory for Monitoring Mechanical Stress on Risk Structures in
      Surgical Training Systems.

PMID- 24043182
TI  - Automatic Adaptation to Post-Movement Eventrelated Synchronization in a Brain
      Computer Interface.

PMID- 24043183
TI  - Variations in Pacing Dynamics Result in Different Heterogeneity and Development
      of Conduction Block.

PMID- 24043184
TI  - Zero Training for BCI - Reality for BCI Systems Based on Event-Related
      Potentials.

PMID- 24043185
TI  - Robot Assisted Walking Affects the Synchrony Between Premotor and Somatosensory
      Areas.

PMID- 24043186
TI  - Novel cap system with active actuators for rapid dry electroencephalography.

PMID- 24043187
TI  - Cortical Activation Patterns of Cue-Paced Foot Movement in Subacute Stroke
      Patients.

PMID- 24043188
TI  - First Results of a New Electromechanical Controlled External Ventricular Drainage
      in a Porcine Model.

PMID- 24043189
TI  - On the use of Non-Invasive Brain-Computer Interface Technology in
      Neurorehabilitation.

PMID- 24043190
TI  - Estimating Brain Connectivity from Single-Trial EEG Recordings.

PMID- 24043191
TI  - BCI and FES Training of a Spinal Cord Injured End-User to Control a
      Neuroprosthesis.

PMID- 24043192
TI  - Applying the user-centred design to evaluation of Brain-Computer Interface
      controlled applications.

PMID- 24043193
TI  - Spatial-Spectral Identification Of MU And Beta Eeg Rhythm Sourcrs During Robot
      Assisted Walking.

PMID- 24043194
TI  - Closed Loop Control of Spontaneous Breathing During Long Term Sedation.

PMID- 24043195
TI  - Single Trial Motor Imagery Classification in EEG Measured During FMRI Image
      Acquisition - A First Glance.

PMID- 24043196
TI  - Introduction of a Universal P300 Brain-Computer Interface Communication System.

PMID- 24043197
TI  - Control of a Mobile Rehabilitation Robot using Exact Feedback Linearisation.

PMID- 24043198
TI  - Think2grasp - BCI-Controlled Neuroprosthesis for the Upper Extremity.

PMID- 24043199
TI  - The hybrid Brain-Computer Interface: a bridge to assistive technology?

PMID- 24043200
TI  - Bioelectric impedance of the neonatal heart during normothermic ischemia.

PMID- 24043201
TI  - Physiological Noise Removal from fNIRS Signals.

PMID- 24043202
TI  - Dark Addapted Pupillary Light Reflex Due to Short Time Laser Beam Exposure.

PMID- 24043203
TI  - Model-Based Ventilator Settings in Pressure Controlled Ventilation.

PMID- 24043204
TI  - Auditorily elicited neural oscillations associated with motor execution, motor
      imagery and non-motor mental tasks.

PMID- 24043205
TI  - Monitoring Bone Density from Patients Undergoing Total Hip Arthroplasty using
      Computed Tomography and 3D Modeling Techniques.

PMID- 24043206
TI  - Current Developments in Automatic Drug Delivery in Anesthesia.

PMID- 24043207
TI  - In vitro cytotoxicity of silver nanoparticles in primary rat hepatic stellate
      cells.
AB  - The number of studies concerning silver nanoparticles (AgNPs) has increased, due
      in part to their potential uses for biomedical applications. These particles have
      been demonstrated in the elimination of the hepatitis B virus and the inhibition
      of the proliferation of various cancer cells in vivo and in vitro. Thus, studies
      on AgNPs may lead to a more efficacious and safer therapeutic approach for
      chronic liver injury. Hepatic stellate cells (HSCs) are essential interstitial
      cells in the liver and are the predominant therapeutic target in hepatic fibrosis
      and liver cirrhosis; however, the intracellular effects of AgNPs on HSCs remain
      to be elucidated. The aim of the present study was to investigate the effects of
      AgNPs on the function and metabolism of HSCs. Various concentrations of AgNPs,
      with a diameter of 10 or 30-50 nm, were incubated with HSCs. Transmission
      electron microscopy, flow cytometry, enzyme-linked immunosorbent assays, and
      apoptosis and proliferation detection kits were used to analyze the effects of
      AgNPs on cell proliferation and metabolism. These studies demonstrated that AgNPs
      inhibited the proliferation of HSCs and induced their apoptosis in a size- and
      dose-dependent manner.

PMID- 24043209
TI  - Why money will not cure under-immunization.
AB  - Societal attitudes about immunization are complex. Attitudes about the finances
      of immunization are, in some ways, even more complex. 

PMID- 24043208
TI  - Sex differences in acute coronary syndrome symptom presentation in young
      patients.
AB  - IMPORTANCE: Little is known about whether sex differences in acute coronary
      syndrome (ACS) presentation exist in young patients and what factors determine
      absence of chest pain in ACS presentation. OBJECTIVES: To evaluate sex
      differences in ACS presentation and to estimate associations between sex,
      sociodemographic, gender identity, psychosocial and clinical factors, markers of
      coronary disease severity, and absence of chest pain in young patients with ACS.
      DESIGN, SETTING, PARTICIPANTS: We conducted a prospective cohort study of 1015
      patients (30% women) 55 years or younger, hospitalized for ACS and enrolled in
      the GENESIS PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From
      Bench to Beyond Premature Acute Coronary Syndrome) study (January 2009-September
      2012). MAIN OUTCOMES AND MEASURES: The McSweeney Acute and Prodromal Myocardial
      Infarction Symptom Survey was administered during hospitalization. RESULTS: The
      median age for both sexes was 49 years. Women were more likely to have non-ST
      segment elevation myocardial infarction (37.5 vs 30.7; P = .03) and present
      without chest pain compared with men (19.0% vs 13.7%; P = .03). Patients without
      chest pain reported fewer symptoms overall and no discernable pattern of non
      chest pain symptoms was found. In the multivariate model, being a woman (odds
      ratio [OR], 1.95 [95% CI, 1.23-3.11]; P = .005) and tachycardia (OR, 2.07 [95%
      CI, 1.20-3.56]; P = .009) were independently associated with ACS presentation
      without chest pain. Patients without chest pain did not differ significantly from
      those with chest pain in terms of ACS type, troponin level elevation, or coronary
      stenosis. CONCLUSIONS AND RELEVANCE: Chest pain was the most common ACS symptom
      in both sexes. Although women were more likely to present without chest pain than
      men, absence of chest pain was not associated with markers of coronary disease
      severity. Strategies that explicitly incorporate assessment of common non-chest
      pain symptoms need to be evaluated.

PMID- 24043210
TI  - Formation of a graphene oxide-DNA duplex-based logic gate and sensor mediated by
      RecA-ssDNA nucleoprotein filaments.
AB  - A conceptually new class of DNA logic gate and biosensor using the complex of a
      graphene oxide-DNA duplex as a scaffold was reported, achieved by means of
      formation of the triple-stranded DNA structure mediated by Recombinational
      protein A (RecA)-ssDNA nucleoprotein filaments with graphene oxide. 

PMID- 24043211
TI  - Whole genome expression profiling and screening for differentially expressed
      cytokine genes in human bone marrow endothelial cells treated with humoral
      inhibitors in liver cirrhosis.
AB  - Bone marrow endothelial cells (BMECs) are important components of the
      hematopoietic microenvironment in bone marrow, and they can secrete several types
      of cytokines to regulate the functions of hematopoietic stem/progenitor cells. To
      date, it is unknown whether BMECs undergo functional changes and lead to
      hematopoietic abnormalities in cases of liver cirrhosis (LC). In the present
      study, whole genome microarray analysis was carried out to detect differentially
      expressed genes in human BMECs treated for 48 h with medium supplemented with 20%
      pooled sera from 26 patients with LC or 10 healthy volunteers as the control
      group. A total of 1,106 upregulated genes and 766 downregulated genes were
      identified. In Gene Ontology analysis, the most significant categories of genes
      were revealed. A large number of the upregulated genes were involved in
      processes, such as cell-cell adhesion, apoptosis and cellular response to stimuli
      and the downregulated genes were involved in the negative regulation of
      secretion, angiogenesis, blood vessel development and cell growth. Pathway
      analysis revealed that the upregulated genes were either cell adhesion molecules
      or parts of the apoptotic signaling pathway and the downregulated genes were
      involved in the Wnt signaling pathway and MAPK signaling pathway. These were the
      pathways with the highest enrichment scores. The results of apoptosis assays
      revealed that the humoral inhibitors in the sera of patients with LC induced the
      apoptosis of BMECs, which confirmed the accuracy of bioinformatic analysis.
      Moreover, we screened and verified 21 differentially expressed cytokine genes
      [transforming growth factor (TGF)B1, tumor necrosis factor (TNF)B, TNF receptor
      superfamily, member 11b (TNFRSF11B), TNF (ligand) superfamily, member 13b
      (TNFSF13B), interleukin (IL)1A, IL6, IL11, IL17C, IL24, family with sequence
      similarity 3, member B (FAM3B), Fas ligand (FASLG), matrix metallopeptidase
      (MMP)3, MMP15, vitronectin (VTN), insulin-like growth factor 1 (IGF1), fibroblast
      growth factor 22 (FGF22), slit homolog 2 (Drosophila) (SLIT2), thrombospondin
      (THBS)2, THBS3, chemokine (C-C motif) ligand 28 (CCL28) and macrophage
      stimulating 1 (MST1)] from 97 cytokine genes in BMECs treated with serum from
      patients with LC. The results from our study demonstrate that the humoral
      inhibitors in the sera of patients with LC induce the dysfunction and abnormal
      cytokine secretion by BMECs, which may be a novel mechanism responsible for
      hematological abnormalities in patients with LC.

PMID- 24043212
TI  - [Molecular biological identification of fungal pathogens in FFPE tissue from
      cases of cephalic mycosis].
AB  - BACKGROUND: Due to the lack of histopathological differentiation the unequivocal
      identification of fungal pathogens is rarely possible. In order to understand the
      pathogen spectrum causing cephalic mycosis the use of alternative methods is
      essential. MATERIAL AND METHODS: In a retrospective study 24 formalin-fixed,
      paraffin-embedded (FFPE) samples from patients with histologically confirmed
      cerebral or cephalic mycosis were analyzed with molecular biological methods.
      RESULTS: In two samples obtained during the patients' lifetime human as well as
      fungal DNA was detected, making an unambiguous diagnosis possible. For tissue
      that had been fixed over a longer period, detection of human and fungal DNA was
      possible merely in 60% and 47 % of the samples, respectively. Most frequently
      diagnosed were aspergillosis (n = 9), followed by mucormycosis (n = 2) and
      imported blastomycosis (n = 1). CONCLUSIONS: Using biopsy material a DNA analysis
      seems promising although only with limited success using brain samples taken at
      autopsy which have been fixed over a longer period. For unambiguous retrospective
      diagnostics of pathogens when cephalic mycosis is suspected, the sample
      extraction for postmortem diagnostics should be performed prior to a long period
      of formalin fixation.

PMID- 24043213
TI  - [PSAP expression in a primary presacral neuroendocrine tumor. Potential for
      confusion with prostate cancer].
AB  - Primary presacral neuroendocrine tumors are a rare entity with less than 30 cases
      described in the literature so far. Here we report of a primary presacral
      neuroendocrine tumor diagnosed at autopsy which was wrongly diagnosed as
      metastasized prostate cancer before. Misdiagnosis was due to the localization of
      the tumor, its morphology and its positivity for prostate-specific acid
      phosphatase (PSAP) when the patient was alive. This is the first report of PSAP
      and somatostatin receptor expression in this type of tumor. 

PMID- 24043214
TI  - An in vitro analysis of intestinal ammonia handling in fasted and fed freshwater
      rainbow trout (Oncorhynchus mykiss).
AB  - Ammonia transport and metabolism were investigated in the intestinal tract of
      freshwater rainbow trout which had been either fasted for 7 days, or fasted then
      fed a satiating meal of commercial trout pellets. In vivo, total ammonia
      concentrations (T amm) in the chyme were approximately 1 mmol L(-1) across the
      entire intestine at 24 h after the meal. Highest chyme pH and P NH3 values
      occurred in the posterior intestine. In vitro gut sac experiments examined
      ammonia handling with mucosal (Jmamm) and serosal (Js amm) fluxes under
      conditions of fasting and feeding, with either background (control <= 0.013 mmol
      L(-1)) or high luminal ammonia concentrations (HLA = 1 mmol L(-1)), the latter
      mimicking those seen in chyme in vivo. Feeding status (fasted or fed) appeared to
      influence ammonia handling by each individual section. The anterior intestine
      exhibited the greatest Jm amm and Js amm values under fasted control conditions,
      but these differences tended to disappear under typical post-feeding conditions
      when total endogenous ammonia production (Jt amm = Js amm - Jm amm, signs
      considered) was greatly elevated in all intestinal sections. Under fasted
      conditions, glutamate dehydrogenase (GDH) and glutaminase (GLN) activities were
      equal across all sections, but the ammonia-trapping enzyme glutamine synthetase
      (GS) exhibited highest activity in the posterior intestine, in contradiction to
      previous literature. Feeding clearly stimulated the total rate of endogenous
      ammonia production (Jt amm), even in the absence of a high luminal ammonia load.
      This was accompanied by an increase in GDH activity of the anterior intestine,
      which was also the site of the largest Jt amm. In all sections, during HLA
      exposure, either alone or in combination with feeding, there were much larger
      increases in endogenous Jt amm, most of which was effluxed to the serosal
      solution. This is interpreted as a response to avoid potential cytotoxicity due
      to overburdened detoxification mechanisms in the face of elevated mucosal
      ammonia. Thus T amm of the intestinal tissue remained relatively constant
      regardless of feeding status and exposure to HLA. Ammonia production by the gut
      may explain up to 18 % of whole-body ammonia excretion in vivo under fasting
      conditions, and 47 % after feeding, of which more than half originates from
      endogenous production rather than from absorption from the lumen.

PMID- 24043216
TI  - Influenza vaccine for 2013-2014.

PMID- 24043215
TI  - Structural model, physiology and regulation of Slr0006 in Synechocystis PCC 6803.
AB  - The slr0006 gene of Synechocystis sp. PCC 6803 is upregulated at mRNA and protein
      level under carbon limitation. The T(N11)A motif in the upstream region of
      slr0006 is a binding site for transcriptional regulator NdhR, and accumulation of
      the Slr0006 protein in ndhR deletion mutant grown in high CO2 suggests that NdhR
      may be a negative regulator of slr0006. Accumulation requires photosynthetic
      electron transfer, because no Slr0006 was detected in darkness or in the presence
      of electron transfer inhibitors DCMU and DBMIB. Structural modeling of the
      Slr0006 protein suggests that it adopts Sua5/YciO/YrdC family fold, which is an
      alpha/beta twisted open-sheet structure. Similar to the structurally known
      members of this protein family, the surface of Slr0006 contains positively
      charged cavity indicating a possible binding site for RNA or nucleotides.
      Moreover, Slr0006 was co-localized with 30S ribosomal proteins and rRNA,
      suggesting involvement in processes linked to protein synthesis. 

PMID- 24043217
TI  - Ado-trastuzumab emtansine (Kadcyla) for HER2-positive metastatic breast cancer.

PMID- 24043218
TI  - In brief: Oxytrol OTC.

PMID- 24043219
TI  - UVA irradiation of fatty acids and their oxidized products substantially
      increases their ability to generate singlet oxygen.
AB  - UVA radiation plays an important role for adverse reactions in human tissue. UVA
      penetrates epidermis and dermis of skin being absorbed by various biomolecules,
      especially endogenous photosensitizers. This may generate deleterious singlet
      oxygen ((1)O2) that oxidizes fatty acids in cell membranes, lipoproteins, and
      other lipid-containing structures such as the epidermal barrier. Indications
      exist that fatty acids are not only the target of (1)O2 but also act as potential
      photosensitizers under UVA irradiation, if already oxidized. Five different fatty
      acids in ethanol solution (stearic, oleic, linoleic, linolenic and arachidonic
      acid) were exposed to UVA radiation (355 nm, 100 mW) for 30 seconds. (1)O2
      luminescence was detected time-resolved at 1270 nm and confirmed in spectrally
      resolved experiments. The more double bonds fatty acids have the more (1)O2
      photons were detected. In addition, fatty acids were continuously exposed to
      broadband UVA for up to 240 min. During that time span, UVA absorption and (1)O2
      luminescence substantially increased with irradiation time, reached a maximum and
      decreased again. HPLC-MS analysis showed that the amount of peroxidized fatty
      acids and the (1)O2 generation increased and decreased in parallel. This
      indicates the high potential of peroxidized fatty acids to produce (1)O2 under
      UVA irradiation. In conclusion, fatty acids along with peroxidized products are
      weak endogenous photosensitizers but become strong photosensitizers under
      continuous UVA irradiation. Since fatty acids and their oxidized products are
      ubiquitous in living cells and in skin, which is frequently and long-lasting
      exposed to UVA radiation, this photosensitizing effect may contribute to
      initiation of deleterious photooxidative processes in tissue. 

PMID- 24043220
TI  - Dual signal amplification strategy for the fabrication of an ultrasensitive
      electrochemiluminescenct aptasensor.
AB  - A dual signal amplification strategy was designed to construct a cathodic
      peroxydisulfate-based electrochemiluminescence (ECL) aptasensor for the
      ultrasensitive detection of thrombin (TB) as a model analyte. The signal was
      amplified by the employment of two kinds of co-reactant, (1) in situ generated
      dissolved O2 from the cascade catalysis of GOD and HRP as co-reactants and (2)
      intercalation of a new co-reactant into the grooves of the dsDNA polymers based
      on the hybridization chain reaction (HCR). Femtomolar levels of TB could be
      detected using the developed aptasensor, with high sensitivity and good
      stability. Thus the S2O8(2-)-O2 ECL system has great potential for development
      and application in clinical diagnostics, immunology and biomedical research. 

PMID- 24043221
TI  - Orthographic recognition in late adolescents: an assessment through event-related
      brain potentials.
AB  - Reading speed and efficiency are achieved through the automatic recognition of
      written words. Difficulties in learning and recognizing the orthography of words
      can arise despite reiterative exposure to texts. This study aimed to investigate,
      in native Spanish-speaking late adolescents, how different levels of orthographic
      knowledge might result in behavioral and event-related brain potential
      differences during the recognition of orthographic errors. Forty-five healthy
      high school students were selected and divided into 3 equal groups (High, Medium,
      Low) according to their performance on a 5-test battery of orthographic
      knowledge. All participants performed an orthographic recognition task consisting
      of the sequential presentation of a picture (object, fruit, or animal) followed
      by a correctly, or incorrectly, written word (orthographic mismatch) that named
      the picture just shown. Electroencephalogram (EEG) recording took place
      simultaneously. Behavioral results showed that the Low group had a significantly
      lower number of correct responses and increased reaction times while processing
      orthographical errors. Tests showed significant positive correlations between
      higher performance on the experimental task and faster and more accurate reading.
      The P150 and P450 components showed higher voltages in the High group when
      processing orthographic errors, whereas N170 seemed less lateralized to the left
      hemisphere in the lower orthographic performers. Also, trials with orthographic
      errors elicited a frontal P450 component that was only evident in the High group.
      The present results show that higher levels of orthographic knowledge correlate
      with high reading performance, likely because of faster and more accurate
      perceptual processing, better visual orthographic representations, and top-down
      supervision, as the event-related brain potential findings seem to suggest. 

PMID- 24043222
TI  - Ionization with low-frequency fields in the tunneling regime.
AB  - Strong-field ionisation surprises with richness beyond current understanding
      despite decade long investigations. Ionisation with mid-IR light has promptly
      revealed unexpected kinetic energy structures that seem related to unanticipated
      quantum trajectories of the electrons. We measure first 3D momentum distributions
      in the deep tunneling regime (gamma = 0.3) and observe surprising new electron
      dynamics of near-zero momentum electrons and extremely low momentum structures,
      below the eV, despite very high quiver energies of 95 eV. Such level of high
      precision measurements at only 1 meV above the threshold, despite 5 orders higher
      ponderomotive energies, has now become possible with a specifically developed
      ultrafast mid-IR light source in combination with a reaction microscope, thereby
      permitting a new level of investigations into mid-IR recollision physics. 

PMID- 24043223
TI  - Rare earth tungstate and molybdate compounds - from 0D to 3D architectures.
AB  - This tutorial review focuses on the recent development of diverse synthetic
      approaches and possibilities for chemical tuning of the size, shape, and
      morphology, as well as properties such as luminescence, of rare earth tungstate
      and molybdate materials. The use of rare earth tungstate and molybdate nano- and
      micromaterials as single materials for the generation of white light is reviewed.
      Additionally, the use of these materials as red phosphors in phosphor-converted
      white light emitting diodes (pc-WLEDs) when employing GaN or InGaN chips as the
      primary light source is explored. 

PMID- 24043224
TI  - Effect of clearance on cartilage tribology in hip hemi-arthroplasty.
AB  - Hemi-arthroplasty of the hip (an artificial femoral head articulating against the
      natural acetabulum) is used to treat fractured necks of femur; however, there is
      evidence that articulation causes erosion of the cartilage, resulting in pain for
      the patient. Parameters that may influence this cartilage erosion include head
      material and roughness, clearance between the head and acetabulum and activity
      levels of the patient. This study has assessed the effect of clearance of hemi
      arthroplasty articulations on the contact stress, friction and cartilage
      deformation in an in vitro tribological simulation of the hemi-arthroplasty joint
      that applied dynamic loads and motion. It has been demonstrated that peak contact
      stress increased from 5.6 to 10.6 MPa as radial clearance increased from small
      (<0.6 mm) to extra-large (>1.8 mm). In all samples, friction factor increased
      with time and was significantly less with extra-large clearances compared to
      small (<0.6 mm), medium (0.6-1.2 mm) and large (1.2-1.8 mm) clearances. The
      cartilage deformation observed was significantly greater in acetabulum samples
      paired to give small or extra-large clearances compared to those with medium or
      large clearances. 

PMID- 24043225
TI  - Methods for reducing peak pressure in laparoscopic grasping.
AB  - During tissue retraction with a laparoscopic grasper, tissue-damaging pressures
      can occur. Past research suggests that peak pressures can be considerably reduced
      by rounding the edges or covering the tip of the end effector with a silicon
      sleeve. To identify grasping methods that limit tissue damage, the effects of (a)
      Young's modulus of the end effector, (b) curvature of the end effector, and (c)
      angle with which the tissue is pulled relative to the plane of the end effector,
      on the pressure generated on the tissue were investigated. Artificial skin was
      placed between two non-serrated jaws, a pressure-sensitive film was interposed
      between the skin and upper jaw, and the end effector was loaded with 13 N. End
      effectors with Young's moduli of 0.09, 0.67, 1.49 MPa, and 69 GPa, and with non
      rounded and 5 mm rounded edges were tested under pulling angles of 25 degrees ,
      50 degrees , and 75 degrees . For non-rounded end effectors, the maximum pressure
      and the area across which pressure exceeded the safety threshold for tissue
      damage increased with Young's modulus and pulling angle. For rounded end
      effectors, maximum pressure did not increase monotonically with Young's modulus.
      Instead, the end effector with the second lowest Young's modulus yielded
      significantly lower maximum pressure than the end effector with the lowest
      Young's modulus. For rounded end effectors, pressures were below the safety
      threshold for all Young's moduli. This indicates that to prevent tissue damage,
      soft graspers may not be needed; rounding the edges of metal graspers could
      suffice for preventing tissue damage.

PMID- 24043226
TI  - Expanding frontiers in canine total joint replacement.

PMID- 24043227
TI  - Analysis of precision in chemical oscillators: implications for circadian clocks.
AB  - Biochemical reaction networks often exhibit spontaneous self-sustained
      oscillations. An example is the circadian oscillator that lies at the heart of
      daily rhythms in behavior and physiology in most organisms including humans.
      While the period of these oscillators evolved so that it resonates with the 24 h
      daily environmental cycles, the precision of the oscillator (quantified via the Q
      factor) is another relevant property of these cell-autonomous oscillators. Since
      this quantity can be measured in individual cells, it is of interest to better
      understand how this property behaves across mathematical models of these
      oscillators. Current theoretical schemes for computing the Q factors show
      limitations for both high-dimensional models and in the vicinity of Hopf
      bifurcations. Here, we derive low-noise approximations that lead to numerically
      stable schemes also in high-dimensional models. In addition, we generalize normal
      form reductions that are appropriate near Hopf bifurcations. Applying our
      approximations to two models of circadian clocks, we show that while the low
      noise regime is faithfully recapitulated, increasing the level of noise leads to
      species-dependent precision. We emphasize that subcomponents of the oscillator
      gradually decouple from the core oscillator as noise increases, which allows us
      to identify the subnetworks responsible for robust rhythms. 

PMID- 24043229
TI  - Five-year experience with burns from glass fireplace doors in the pediatric
      population.
AB  - Burns from contact with glass doors of gas fireplaces have been previously
      reported. The purpose of this study is to examine the incidence and severity of
      this injury in our population. Patients were identified for inclusion in the
      retrospective chart review study using the National Trauma Registry of the
      American College of Surgeons (NTRACS) and our local outpatient database. Criteria
      for inclusion were burn injuries sustained from contact with fireplace glass
      doors treated at our pediatric burn center from 2007 through 2011. Fifty children
      met these criteria, including two children whose burns were caused by electric
      fireplace glass doors. BSA burned was 1.5 +/- 1.5% (mean +/- SD), range 0.5 to
      10%. Age was 27.2 +/- 27.3 months, range 8 months to 13 years. Forty-five
      children (90%) had hand burns; of these, 18 children had bilateral hand
      involvement. Facial burns were found in three children (6%), and eight children
      (16%) had other areas burned. One patient developed cellulitis. Two patients
      required surgery. Six children (12%) required hospitalization; mean length of
      stay was 5.8 +/- 5 days, range 1 to 5 days. Although the number of inpatient
      admissions was relatively few, 329 outpatient visits and 309 rehabilitation
      visits were required for treatment of these children. Nineteen patients (38%)
      required splints and six patients (12%) required scar treatment with pressure
      garments. Burns from contact with fireplace glass doors are a recurring problem.
      Toddlers are most at risk. Directed preventive strategies including parent
      education, safety warnings, and design modifications such as temperature sensors
      and barrier screens could be potentially helpful in reducing the incidence of
      this injury. 

PMID- 24043228
TI  - High-density livestock operations, crop field application of manure, and risk of
      community-associated methicillin-resistant Staphylococcus aureus infection in
      Pennsylvania.
AB  - IMPORTANCE: Nearly 80% of antibiotics in the United States are sold for use in
      livestock feeds. The manure produced by these animals contains antibiotic
      resistant bacteria, resistance genes, and antibiotics and is subsequently applied
      to crop fields, where it may put community members at risk for antibiotic
      resistant infections. OBJECTIVE: To assess the association between individual
      exposure to swine and dairy/veal industrial agriculture and risk of methicillin
      resistant Staphylococcus aureus (MRSA) infection. DESIGN, SETTING, AND
      PARTICIPANTS: A population-based, nested case-control study of primary care
      patients from a single health care system in Pennsylvania from 2005 to 2010.
      Incident MRSA cases were identified using electronic health records, classified
      as community-associated MRSA or health care-associated MRSA, and frequency
      matched to randomly selected controls and patients with skin and soft-tissue
      infection. Nutrient management plans were used to create 2 exposure variables:
      seasonal crop field manure application and number of livestock animals at the
      operation. In a substudy, we collected 200 isolates from patients stratified by
      location of diagnosis and proximity to livestock operations. MAIN OUTCOMES AND
      MEASURES: Community-associated MRSA, health care-associated MRSA, and skin and
      soft-tissue infection status (with no history of MRSA) compared with controls.
      RESULTS: From a total population of 446,480 patients, 1539 community-associated
      MRSA, 1335 health care-associated MRSA, 2895 skin and soft-tissue infection
      cases, and 2914 controls were included. After adjustment for MRSA risk factors,
      the highest quartile of swine crop field exposure was significantly associated
      with community-associated MRSA, health care-associated MRSA, and skin and soft
      tissue infection case status (adjusted odds ratios, 1.38 [95% CI, 1.13-1.69],
      1.30 [95% CI, 1.05-1.61], and 1.37 [95% CI, 1.18-1.60], respectively); and there
      was a trend of increasing odds across quartiles for each outcome (P <= .01 for
      trend in all comparisons). There were similar but weaker associations of swine
      operations with community-associated MRSA and skin and soft-tissue infection.
      Molecular testing of 200 isolates identified 31 unique spa types, none of which
      corresponded to CC398 (clonal complex 398), but some have been previously found
      in swine. CONCLUSIONS AND RELEVANCE: Proximity to swine manure application to
      crop fields and livestock operations each was associated with MRSA and skin and
      soft-tissue infection. These findings contribute to the growing concern about the
      potential public health impacts of high-density livestock production.

PMID- 24043230
TI  - The impact of prediabetes on glycemic control and clinical outcomes postburn
      injury.
AB  - Poor glucose control and clinical outcomes have been observed in diabetic versus
      nondiabetic patients postburn injury. Prediabetes is a precursor to diabetes. The
      purpose of this study was to assess the effects of prediabetes on postinjury
      glucose control and clinical outcomes. A retrospective review was conducted
      comparing prediabetics and euglycemic controls. Patients who were admitted for
      burn care were 18 to 89 years of age and had a hemoglobin A1c (HbA1c) obtained on
      admission. Prediabetics were defined by an HbA1c of 5.7 to 6.4% and controls by
      HbA1c < 5.7%. Inpatient glucose levels were recorded, in addition to clinical
      outcomes. Two hundred eight patients were included: 54 prediabetics and 154
      controls. The prediabetic population was older (50.7 vs 39 years; P < .001) with
      more hypertensives (44.4 vs 16.9%; P < .001), consisted of more African-Americans
      (20.4 vs 12%; P = .04), and had larger areas of full-thickness burns (4.5 vs
      1.75%; P = .02). Median admission HbA1c was 5.9 (5.7-6.0)% among prediabetics and
      5.3 (5-5.45)% among controls (P < .001). Prediabetics had significantly higher
      time-weighted glucose levels (127.7 [105.5-147.6] vs 108.0 [97.1-122.2] mg/dl; P
      < .001) and more had an average inpatient glucose >150 mg/dl (20.4 vs 9.1%; P =
      .028). There was no difference in rates of hypoglycemia (glucose <70 mg/dl) or
      glycemic variability. Prediabetics had lower survival rates (92.6 vs 98.7%; P =
      .041), but similar rates of unplanned readmission (1.9 vs 3.9%; P = .68),
      intensive care unit admission (29.6 vs 23.4%; P = .36), mechanical ventilation
      (24.1 vs 16.2%; P = .20), length of hospital stay (4 [2-8] vs 3 [2-11]; P = .71),
      and infection (11.1 vs 11.7%; P = .99). Prediabetic status has a significant
      impact on glucose control and mortality after burn injury. 

PMID- 24043231
TI  - April 2013, from Massachusetts to Texas, disasters that remind us of our own
      preparedness needs.

PMID- 24043232
TI  - Inhibition of hyaluronan synthase 2 reduces the abnormal migration rate of keloid
      keratinocytes.
AB  - Keloids are fibroproliferative scars that spread beyond the original wound
      boundary and are very resistant to treatment. Development of highly effective
      therapies requires a comprehensive understanding of the mechanisms regulating
      keloid formation. Previous studies indicated that keloid keratinocytes have
      abnormal expression of genes involved in differentiation and adhesion, and
      increased migration rates. The objective of the current study was to better
      understand the role of hyaluronan synthase 2 (HAS2) in keloid keratinocyte
      migration and gene expression. Keratinocytes were isolated from keloid scars and
      normal skin. Migration rates of keloid keratinocytes were quantified using an in
      vitro scratch assay. Expression levels of HAS2, related HAS1, and HAS3 genes, and
      genes aberrantly expressed in keloid keratinocytes, were quantified using real
      time polymerase chain reaction. Treatment with 4-methylumbelliferone (4MU) was
      used to inhibit hyaluronic acid synthesis. The expression of HAS2 was
      significantly increased in keloid vs normal keratinocytes. Treatment with 4MU
      caused a dose-dependent reduction in keloid keratinocyte migration and HAS2
      expression; HAS3 expression was moderately inhibited by 4MU and HAS1 was not
      expressed. Keloid keratinocytes displayed a motile phenotype in vitro, including
      loose colonies and widely separated refractile cells; this phenotype was
      normalized by 4MU. Further, 4MU altered gene expression in keloid keratinocytes.
      The results suggest that HAS2 overexpression contributes to increased migration
      and altered gene expression in keloid keratinocytes. Abnormal keratinocyte
      migration may contribute to the overhealing of keloid scars beyond the original
      wound boundaries. Therefore, inhibition of HAS2 expression using 4MU may
      represent a novel strategy for treatment of keloid scarring. 

PMID- 24043233
TI  - Enoxaparin and antifactor Xa levels in pediatric acute burn patients.
AB  - Previous work from the authors' group showed a risk for inadequate enoxaparin
      dosing for venous thromboembolism prophylaxis in adult burn patients when
      traditional recommendations are used. The purpose of this study was to determine
      whether this also applied to pediatric burn patients. Included patients were
      acutely burned, aged 14 years or under, and admitted to the authors' regional
      burn center between October 1, 2004 and December 15, 2012. Thirty-five patients
      included in this analysis received enoxaparin for venous thromboembolism
      prophylaxis dosed initially at 0.5 mg/kg and monitored with anti-factor Xa levels
      (anti-Xa) between 0.2 and 0.4U/ml. Of the included patients, 80% were male with a
      median age of 8 years, a median TBSA of 16%, and a median length of stay of 23
      days. Initially 21 patients (60%) had an undetectable anti-Xa (<0.2 U/ml).
      Enoxaparin doses were increased but 18 patients (51%) never achieved target anti
      Xa. There were no significant differences in sex, weight, dose, depth of injury,
      or body mass index between those who received appropriate prophylaxis and those
      who were undertreated. However, median size of burn was significantly larger,
      median age and height were significantly lower in those who did not reach target.
      The low number of patients achieving target prophylactic anti-Xa in this study
      demonstrates the need for routine anti-Xa monitoring in pediatric burns.
      Additionally, pediatric patients with major burn injury may require initial
      dosing of enoxaparin greater than published recommendations because of altered
      pharmacokinetics. 

PMID- 24043234
TI  - Rapid response team implementation on a burn surgery/acute care ward.
AB  - To date there is limited evidence of efficacy for rapid response teams (RRT) in
      burns despite widespread their implementation in U.S. hospitals. The burn
      surgery/acute care ward at the Harborview Medical Center, Seattle, Washington,
      primarily treats burns, acute wounds, and pediatric trauma patients, but also
      accepts overflow surgical and medical patients. The authors hypothesize that
      institutional RRT implementation in 2006 has reduced code blue activations,
      unplanned intensive care unit (ICU) transfers, and mortality on the acute care
      ward of this hospital. The authors retrospectively analyzed all patients treated
      in our acute care unit before (2000-2004) and after RRT implementation (2007
      2011). Patient, injury, and treatment outcomes information were collected and
      analyzed. The authors specifically examined clinical signs that triggered RRT
      activation and processes of care after activation. They compared code blue
      activation rates, unplanned ICU transfers, and mortality between the two periods
      by Poisson regression. The acute care unit treated 7092 patients before and 9357
      patients after RRT implementation. There were 409 RRT activations in 329
      patients, 18 of whom ultimately died during hospitalization. Those who died had
      higher rates of stridor (P = .03), tachypnea (P = .001), and low oxygen
      saturations (P = .02) compared with survivors. Fewer burn and surgical patients
      died after implementation (seven patients; 22% of all deaths) compared with
      patients who died pre-RRT (27 patients; 53% of all deaths). After adjustment for
      case-mix index, age, and medical service differences between the two periods,
      code blue calls decreased from 1.4/1000 to 0.4/1000 admissions (P = .04),
      unplanned ICU transfer rates decreased from 65/1000 to 50/1000 admissions (P <
      .01), and hospital deaths decreased from 4.5/1000 to 3.3/1000 admissions (P =
      .11). Since its implementation, RRT activation has been frequently used in the
      acute care ward of this hospital. Respiratory symptoms distinguish RRT patients
      who die during hospitalization compared with survivors. RRT implementation was
      associated with fewer code blue activations, unplanned ICU transfers, and a trend
      toward reduced in-hospital deaths, particularly in burn and surgical patients. 

PMID- 24043235
TI  - Regional neurovascular inflammation and apoptosis are detected after electrical
      contact injury.
AB  - High-voltage electrical injuries are a devastating form of trauma often treated
      in burn centers. Examining superficial wounds alone may lead to an inaccurate
      assessment of local, regional, and systemic severity of injury. In this work, the
      neurovasculature at sites regionally distinct from the contact wound were
      assessed for cellular pathology. Nine male Sprague-Dawley rats subjected to 1000
      V direct-current shocks were separated into three groups: high-shock (>10-second
      contact), low-shock (<4-second contact), and control. Injury video was captured
      with a forward-looking infrared camera, and a thermal excitation analysis was
      performed. The neurovascular bundles from the iliofemoral region to the distal
      posterior tibial region were dissected from the hind limbs of the shocked animals
      and stained by immunohistochemistry for antibodies specific to apoptosis (APO) 1,
      caspase-3, activating transcription factor 3, high-mobility group box-1,
      granulocyte-macrophage colony-stimulating factor and interleukin-6. Real-time
      reverse-transcription polymerase chain reaction was used to quantify differential
      transcript levels of superoxide dismutases 1, 2, and 3 and heat-shock protein 70
      from peripheral blood mononuclear cells and liver tissue. Finally, a protein
      array was used to identify key inflammatory cytokines in blood plasma.
      Significant dose-dependent trends were identified in apoptotic markers as well as
      inflammatory markers in both arterial and nerve tissues. Although arterial tissue
      exhibited a gradual decline in these markers proximally from the wound site,
      nerve tissue maintained a constant level at every location. Transcript analysis
      revealed an up-regulation of extracellular superoxide dismutase, and down
      regulation of heat-shock protein 70, whereas plasma inflammatory cytokine levels
      indicated no significant changes. Thermal excitation analysis revealed a linear
      temperature increase, with a dose-dependent thermal maximum. In this study the
      authors have shown that neurovascular APO and inflammation are present at
      locations extremely proximal to electrical injury contact sites and this appears
      to be dose-dependent. Nerve tissue APO and inflammation may extend farther
      proximally than the iliofemoral region, and multiple proapoptotic mechanisms may
      be activated. No systemic inflammatory response was indicated in this study. 

PMID- 24043236
TI  - Flaming alcoholic drinks: flirting with danger.
AB  - Alcohol-related burn injuries carry significant mortality and morbidity rates.
      Flaming alcoholic beverages served in trendy bars and clubs are becoming
      increasingly popular. The dangers associated with an ignited alcoholic drink are
      often underestimated by party goers whose risk assessment ability is already
      impaired by heavy alcohol consumption. The authors present two cases
      demonstrating the varied severity of burn injuries associated with flaming
      alcoholic drinks, and their clinical management. Consumption of flaming alcoholic
      drinks poses potential risks for burn injuries. Further support is required to
      enable national and local agencies to implement effective interventions in
      drinking environments. 

PMID- 24043237
TI  - Determination of tobramycin pharmacokinetics in burn patients to evaluate the
      potential utility of once-daily dosing in this population.
AB  - The objective was to determine the pharmacokinetics of tobramycin in critically
      ill adult burn patients and evaluate a variety of milligram per kilogram (mg/kg)
      total body weight (TBW) regimens to determine whether practical initial once
      daily administration recommendations to attain desired plasma levels could be
      identified. A retrospective study was conducted in 58 eligible patients who
      received tobramycin and had at least one set of steady-state levels from which
      pharmacokinetic parameters could be determined using standard first-order
      pharmacokinetic equations. Classification and Regression Tree analysis was used
      to identify whether tobramycin clearance changed with time postburn. Monte Carlo
      Simulation was used to evaluate initial mg/kg TBW dosing regimens to determine
      whether a clinically useful once-daily tobramycin recommendation could be made.
      Tobramycin clearance was significantly greater for patients <=45 days postburn vs
      patients >45 days postburn. Once-daily tobramycin dosing for patients <=45 days
      postburn of 10 to 13 mg/kg TBW and for patients >45 days postburn of 8 to 10
      mg/kg TBW provided levels similar to those known to be effective in nonburn
      injury patients. Once-daily tobramycin dosing recommendations for burn patients
      were determined. Variability in pharmacokinetics in this population and change in
      pharmacokinetics with time postburn injury necessitate monitoring of tobramycin
      levels to ensure targets are met and maintained. 

PMID- 24043239
TI  - Skin necrosis as a complication of therapeutic hypothermia.
AB  - This case report describes a complication caused by cooling pads used for
      therapeutic hypothermic resuscitation. The authors hope to highlight and
      emphasize the importance of a thorough evaluation of all skin surfaces that are
      in direct contact with such cooling pads. Skin injury from the cooling pads used
      for therapeutic hypothermia should be recognized as a potential complication of
      treatment. 

PMID- 24043238
TI  - A simple cost-saving measure: 2.5% mafenide acetate solution.
AB  - The optimal concentration of mafenide acetate solution for use in the treatment
      of burns is unknown. Despite data supporting the use of a 2.5% solution, 5%
      formulation is traditionally used, and has been the highest-costing medication on
      formulary. The aim of the current study is to evaluate cost and patient outcomes
      associated with a new policy implementing the use of 2.5% solution in burn
      patients and restricting the 5% formulation to specific indications only. A
      retrospective review of all patients receiving mafenide acetate solution at a
      single pediatric burn hospital was performed before and after the initiation of
      the new policy on the use of 5 vs 2.5% solution. Duration of therapy, adverse
      events, cost, incidence of wound infection, and bacteremia were analyzed. In
      2009, 69 patients were treated with 5% mafenide acetate solution for a total cost
      of $125,000 ($1811 per patient). In 2010, after the initiation of the policy, 48
      patients were treated: 19 received 5% mafenide acetate solution with appropriate
      indication, whereas the remaining 29 received 2.5% solution for a total cost of
      $38,632 ($804 per patient). There were no significant changes in the incidence of
      bacteremia or wound infection. No side effects of either solution were noted.
      Under certain conditions, a 2.5% mafenide acetate solution appears sufficient. In
      this multinational pediatric burn hospital, the use of a 2.5% solution was not
      associated with increased bacteremia or wound infection, and proved to be more
      cost-effective. 

PMID- 24043240
TI  - Does recombinant factor XIII eliminate early manifestations of multiple-organ
      injury after experimental burn similarly to gut ischemia-reperfusion injury or
      trauma-hemorrhagic shock?
AB  - The authors have previously shown that recombinant factor XIII (rFXIII)
      eliminates early manifestations of multiple-organ injury caused by experimental
      superior mesenteric artery occlusion or trauma-hemorrhagic shock. The aim of the
      present study was to test the hypothesis that rFXIII provides similar protective
      effect in experimental burn injury. Rats were randomly divided into five groups
      (eight animals per group): group 1: burn + placebo treatment; group 2: burn +
      rFXIII pretreatment; group 3: burn + rFXIII treatment; group 4: sham burn +
      placebo treatment, and group 5: sham burn + rFXIII treatment. Burn (40% of TBSA)
      was achieved by immersing the back and abdomen of a rat into 97 degrees C water
      for 10 and 5 seconds, respectively. Infusion of rFXIII (1 mg/kg) or placebo was
      performed immediately after burn/sham burn in treatment groups or 24 hours before
      burn and repeated immediately after it in pretreatment group. Endpoint parameters
      measured 3 hours after burn/sham burn included muscle blood flow and PO2, lung
      permeability, gut histology, lung and gut myeloperoxidase activity, neutrophil
      respiratory burst, and FXIII activity. Both treatment and pretreatment with
      rFXIII partially preserved microvascular blood flow in the muscle. Muscle PO2 in
      pretreated rats did not differ from that in shams. Pretreatment but not treatment
      with rFXIII preserved lung permeability. rFXIII did not have any protective
      effect on other endpoint parameters. In contrast to superior mesenteric artery
      occlusion and trauma-hemorrhagic shock experimental models, rFXIII at the doses
      tested has a limited effect on preventing early manifestations of multiple-organ
      injury after experimental burn. 

PMID- 24043241
TI  - Aerobic Fitness Is Disproportionately Low in Adult Burn Survivors Years After
      Injury.
AB  - A maximal aerobic capacity below the 20th percentile is associated with an
      increased risk of all-cause mortality (Blair 1995). Adult Adult burn survivors
      have a lower aerobic capacity compared with nonburned adults when evaluated 38 +/
      23 days postinjury (deLateur 2007). However, it is unknown whether burn
      survivors with well-healed skin grafts (ie, multiple years postinjury) also have
      low aerobic capacity. This project tested the hypothesis that aerobic fitness, as
      measured by maximal aerobic capacity (VO2max), is reduced in well-healed adult
      burn survivors when compared with normative values from nonburned individuals.
      Twenty-five burn survivors (36 +/- 12 years old; 13 females) with well-healed
      split-thickness grafts (median, 16 years postinjury; range, 1-51 years) covering
      at least 17% of their BSA (mean, 40 +/- 16%; range, 17-75%) performed a graded
      cycle ergometry exercise to test volitional fatigue. Expired gases and minute
      ventilation were measured via a metabolic cart for the determination of VO2max.
      Each subject's VO2max was compared with sex- and age-matched normative values
      from population data published by the American College of Sports Medicine, the
      American Heart Association, and recent epidemiological data (Aspenes 2011).
      Subjects had a VO2max of 29.4 +/- 10.1 ml O2/kg body mass/min (median, 27.5;
      range, 15.9-53.3). The use of American College of Sports Medicine normative
      values showed that mean VO2max of the subjects was in the lower 24th percentile
      (median, 10th percentile). A total of 88% of the subjects had a VO2max below
      American Heart Association age-adjusted normative values. Similarly, 20 of the 25
      subjects had a VO2max in the lower 25% percentile of recent epidemiological data.
      Relative to nongrafted subjects, 80 to 88% of the evaluated skin-graft subjects
      had a very low aerobic capacity. On the basis of these findings, adult burn
      survivors are disproportionally unfit relative to the general U.S. population,
      and this puts them at an increased risk of all-cause mortality (Blair 1995). 

PMID- 24043242
TI  - Predictors of serious bacterial infections in pediatric burn patients with fever.
AB  - To determine predictors of serious bacterial infections in pediatric burn
      patients with fever (core temp >=38.5 degrees C), the authors conducted a
      retrospective review of medical records of pediatric (0-18 years) patients
      admitted to the Arizona Burn Center between 2008 and 2011 with greater than 5%
      TBSA and inpatient hospitalization for >=72 hours. The study group comprised
      patients with a febrile episode during their inpatient stay. Serious bacterial
      infection (the primary outcome variable) was defined as: bacteremia, urinary
      tract infection, meningitis (blood, urine, or cerebrospinal fluid culture
      positive for a pathogen respectively), pneumonia, line, and wound infection. A
      generalized estimating equation analysis was done to predict the presence or
      absence of serious bacterial infection. Of 1082 pediatric burn patients
      hospitalized during the study period, 353 met the study eligibility criteria. A
      total of 108 patients (30.6%) had at least one fever episode (fever group). No
      difference in demographic characteristics was noted between the fever and no
      fever groups; significant differences were observed for: third-degree TBSA,
      second-degree TBSA, total operating room visits, length of stay, Injury Severity
      Score, and death. A total of 47.2% of the patients had one or more episodes of
      fever with serious bacterial infection. In a generalized estimating equation
      predictive model, presence of a central line, second-, and third-degree TBSA were
      predictive of serious bacterial infection in burn patients with fever. In this
      study, individual clinical variables such as tachypnea and tachycardia were not
      predictive of serious bacterial infections, but the presence of a central line,
      and larger TBSA were significant predictors of serious bacterial infections.
      Younger age (P =.08) and ventilator support (P =.057) also approached
      significance as predictors of serious bacterial infections. 

PMID- 24043243
TI  - Amish burn ointment and burdock leaf dressings: assessments of antimicrobial and
      cytotoxic activities.
AB  - Amish burn wound ointment (ABO) contains honey, lanolin, oils, glycerin, bees
      wax, and other natural additives. Although there are many anecdotal reports that
      this ointment covered with a burdock leaf (BL) dressing promotes burn wound
      healing, little scientific testing of this treatment has occurred. The goal of
      this study was to evaluate in vitro some of the components of this treatment
      modality for antimicrobial and cytotoxic activities. The ABO was tested for
      sterility using standard microbiological techniques. Because of the semisolid,
      lipid-based nature of the salve, the at-use product could not be tested in
      bioassays. Samples of BL and the dry ingredients (DI) used in the ointment were
      provided by the Amish vendor. Aqueous extracts of the DI and of the BL were
      prepared and freeze dried. The freeze-dried extracts were reconstituted,
      filtered, and tested separately on keratinocyte and fibroblast cell cultures for
      cytotoxicity (growth inhibition assay) and against a panel of susceptible and
      resistant microbes for antimicrobial activity (Nathan's agar-well diffusion
      assay) in a series of concentrations (% wt/vol). Neither DI nor BL extracts
      demonstrated antimicrobial activity against any of organisms tested. The DI
      extract inhibited growth of both keratinocytes and fibroblasts at the 0.1%
      concentration. The 0.1 and 0.03% concentrations of the BL extract were cytotoxic
      to both keratinocytes and fibroblasts. Although tests for microbial growth from
      the at-use preparation of the ABO were negative, extracts of the DI and BL did
      not demonstrate any antimicrobial activity. Additionally, both extracts inhibited
      the growth of skin cells in vitro at higher concentrations. These results suggest
      caution in the use of ABO and BL dressings if there is more than a minimal risk
      of complications from the burn injury. 

PMID- 24043244
TI  - Proximally based sural adipose-cutaneous/scar flap in elimination of ulcerous
      scar soft-tissue defect over the achilles tendon and posterior heel region: a new
      approach.
AB  - Scar ulcers that spread over the Achilles tendon and posterior heel disturb
      patients by causing pain, impeding hygiene, and creating difficulty in finding
      appropriate shoe wear. As this region undergoes pressure, effective
      reconstruction is based on the flap use. The most popular flaps currently used
      are distally based sural fasciocutaneous flap, calcaneal artery skin flap, and
      free flaps. These flaps, however, are insensate, can create soft-tissue excess,
      and cause donor site morbidity. Ulcerous soft-tissue defects over Achilles tendon
      and posterior heel after burns, frost, and trauma were studied and reconstructed
      in 16 patients, using proximally based sural adipose-cutaneous flap, the anatomy
      of which was studied on lower extremities of 27 cadavers. Ulcerous soft-tissue
      defect consists of two parts: ulcer and surrounding pathologic scars that should
      be excised in one block. Resulting soft-tissue defects with exposed tendon and
      calcaneal bone varied from 6 to 20 cm in length and 6 cm in width. For such wound
      resurfacing a flap was developed that was sensate, thin, large, and having steady
      blood circulation. The flap was harvested from the lower third of the leg and
      lateral foot, consisting of skin and subcutaneous fat layer (without fascia),
      including the sural nerve and lesser vein. The blood supply was ensured through
      peroneal and anterior tibial artery perforators, which formed a vascular net in
      the flap. In 14 of 16 cases excellent and stable functional and good cosmetic
      results with acceptable donor site morbidity were achieved. In two patients the
      distal flap loss took place because of arteriitis obliterans (one case) and
      because of the cross-cutting of the sural nerve and vessels during previous
      surgeries (another case). Proximally based sural adipose-cutaneous/scar flap is
      the only flap that satisfies all requirements for Achilles tendon and posterior
      heel region resurfacing. The author believes that this technique, based on this
      flap use, is anatomically justified, clinically profitable, and should be
      considered as the first choice operation. 

PMID- 24043245
TI  - Evaluation of an enoxaparin dosing calculator using burn size and weight.
AB  - Previous research has shown that inadequate antifactor Xa levels (anti-Xa) occur
      in burn patients and may increase the risk of venous thromboembolic events (VTE).
      The objective of this retrospective review was to investigate the usefulness of
      an enoxaparin dosing algorithm using a previously published equation. With
      institutional review board approval, all acute burn patients at an American Burn
      Association-verified regional burn center who were treated with enoxaparin for
      VTE prophylaxis and had at least one anti-Xa from May 1, 2011 to December 15,
      2012 were included. Patients with subprophylactic anti-Xa received increased
      enoxaparin dose per unit protocol with the goal of obtaining a prophylactic anti
      Xa (0.2-0.4 U/ml). Sixty-four patients were included in our analysis. The
      regression equation was used in 33 patients for initial enoxaparin dosing (Eq)
      whereas 31 patients received traditionally recommended prophylaxis dosing (No
      Eq). Groups were comparable in sex, age, weight, inhalation injury, and burn
      size. Initial enoxaparin dosing in Eq was significantly more likely to reach
      target than in No-Eq (73 vs 32%; P = .002). No episodes of hemorrhage,
      thrombocytopenia, or heparin sensitivity were documented in either group. Median
      final enoxaparin dose required to reach prophylactic level was 40 mg every 12
      hours (range, 30-80 mg). Twenty-one No-Eq patients ultimately reached target, and
      11 of these final doses were equivalent to or greater than the predicted
      equation. Ten patients never reached prophylactic anti-Xa before enoxaparin was
      discontinued (nine from No-Eq). Two patients, one from each group, developed VTE
      complications despite appropriate anti-Xa for prophylaxis. A strong correlation
      was shown between weight, burn size, and enoxaparin dose (r = .68; P < .001). Use
      of the enoxaparin dosing algorithm significantly increased the frequency of
      obtaining a target initial anti-Xa. There were no bleeding complications.
      Enoxaparin dosing correlates to burn size and weight, making a standard dose
      inappropriate because patient habitus and extent of burn injury are highly
      variable. This simple equation improves enoxaparin dosing for acute adult burn
      patients. 

PMID- 24043246
TI  - Burn prevention in Zambia: a work in progress.
AB  - The aim of this study was to assess both burn prevention knowledge and the
      effectiveness of educational intervention in alleviating the current knowledge
      deficit in Zambian youth. In one rural Zambian district, a burn prevention
      program was implemented in June 2011. Children at two elementary schools
      completed a 10-question survey that aimed to assess knowledge regarding burn
      injuries. After completing the survey, children received a burn and fire safety
      presentation and a burn prevention coloring book. Children were reassessed in May
      2012 using the same survey to determine program efficacy and knowledge retention.
      Burn knowledge assessments were also completed for children at other schools who
      did not receive the burn prevention program in 2011. Logistic regression analysis
      was used for statistical adjustment for confounding variables. Between June 2011
      and May 2012, 2747 children from six schools were assessed for their burn
      knowledge, with 312 of them resurveyed after educational intervention since
      initial survey. Reassessed children performed significantly better on three
      questions after controlling for confounders. They did better on five questions
      but their performance on these failed to achieve statistical significance.
      Children performed significantly worse on one concept about first aid treatment
      of a burn. A majority of the children demonstrated knowledge deficit in three
      concepts, even after educational intervention. There is a large variation in
      first burn knowledge survey performance of children from different schools, with
      inconsistency between concepts. With half the questions, knowledge deficit did
      not improve with advancement in school grade. Low- and moderate-income countries
      (LMICs) face the largest burns burden. With the lack of adequate burn care facing
      LMICs, burn injury prevention is of particular importance in those countries.
      This study shows that burn educational intervention could be effective in
      reducing burn knowledge deficit; however, the residual deficit posteducation
      could still be large and potentially contributing to heightened burn injury
      incidence. Customized and integrated educational programs may be proposed
      regarding the epidemiological profile of burn knowledge deficit from various
      schools. This study represents one of the few reports on the effectiveness of a
      burn prevention program in an LMIC. Future epidemiological data will be needed
      from nearby healthcare facilities to determine whether this program decreased
      burn morbidity and mortality at the hospital level. 

PMID- 24043247
TI  - Alterations in the expression of atrial calpains in electrical and structural
      remodeling during aging and atrial fibrillation.
AB  - The aim of this study was to investigate the correlation between the change in
      the expression of atrial calpains and electrical, molecular and structural
      remodeling during aging and atrial fibrillation (AF). Adult and aged canines in
      sinus rhythm (SR) and with persistent AF (induced by rapid atrial pacing) were
      investigated. A whole-cell patch clamp was used to measure the L-type Ca2+
      current (ICa-L) in cells in the left atrium. The mRNA and protein expression of
      the L-type calcium channel alc subunit (LVDCCa1c) and calpains were measured by
      quantitative (q)PCR and western blot analysis. Histopathological and
      ultrastructural changes were analyzed via light and electron microscopy. The
      quantity of apoptotic myocytes was determined by a terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling (TUNEL) assay. In SR groups, atrial
      cells of the aged canines exhibited a longer action potential (AP) duration to
      90% repolarization (APD90), lower AP plateau potential and peak ICa-L current
      densities (P<0.05). In the adult and aged groups, AF led to a higher maximum
      diastolic potential, an increase in AP amplitude and decreases in APD90, AP
      plateau potential and peak ICa-L densities (P<0.05). Compared with the control
      group, the mRNA and protein expression levels of LVDCCa1c were decreased in the
      aged groups; however, the mRNA and protein expression of calpain 1 was increased
      in the adult and the aged groups with AF (P<0.05). Samples of atrial tissue
      exhibited abnormal histopathological and ultrastructural changes, such as
      accelerated fibrosis and apoptosis with aging and in AF. Age-related alterations
      in atrial tissues were attributed to the increased expression of calpain 1. The
      general pathophysiological alterations in normal aged atria may therefore produce
      a substrate that is conducive to AF.

PMID- 24043249
TI  - Caveolin-1 scaffolding domain promotes leukocyte adhesion by reduced basal
      endothelial nitric oxide-mediated ICAM-1 phosphorylation in rat mesenteric
      venules.
AB  - Exogenously applied caveolin-1 scaffolding domain (CAV) has been shown to inhibit
      inflammatory mediator-induced nitric oxide (NO) production and NO-mediated
      increases in microvessel permeability. However, the effect of CAV on endothelial
      basal NO that prevents leukocyte adhesion remains unknown. This study aims to
      investigate the roles of exogenously applied CAV in endothelial basal NO
      production, leukocyte adhesion, and adhesion-induced changes in microvessel
      permeability. Experiments were conducted in individually perfused rat mesenteric
      venules. Microvessel permeability was determined by measuring hydraulic
      conductivity (Lp). NO was quantified with fluorescence imaging in DAF-2-loaded
      vessels. Perfusing venules with CAV inhibited basal NO production without
      affecting basal Lp. Resuming blood flow in CAV-perfused vessels significantly
      increased leukocyte adhesion. The firmly adherent leukocytes altered neither
      basal Lp nor adherens junction integrity. Increases in Lp occurred only upon
      formyl-Met-Leu-Phe application that induces release of reactive oxygen species
      from the adherent leukocytes. The application of NO synthase inhibitor showed
      similar results to CAV, and NO donor abolished CAV-mediated leukocyte adhesion.
      Immunofluorescence staining showed increases in binding of ICAM-1 to an adhesion
      blocking antibody concurrent with a Src-dependent ICAM-1 phosphorylation
      following CAV perfusion. Pre-perfusing vessels with anti-ICAM-1 blocking antibody
      or a Src kinase inhibitor attenuated CAV-induced leukocyte adhesion. These
      results indicate that the application of CAV, in addition to preventing excessive
      NO-mediated permeability increases, also causes reduction of basal NO and
      promotes ICAM-1-mediated leukocyte adhesion through Src activation-mediated ICAM
      1 phosphorylation. CAV-induced leukocyte adhesion was uncoupled from leukocyte
      oxidative burst and microvessel barrier function, unless in the presence of a
      secondary stimulation.

PMID- 24043248
TI  - Role of mitochondrial oxidative stress in hypertension.
AB  - Based on mosaic theory, hypertension is a multifactorial disorder that develops
      because of genetic, environmental, anatomical, adaptive neural, endocrine,
      humoral, and hemodynamic factors. It has been recently proposed that oxidative
      stress may contribute to all of these factors and production of reactive oxygen
      species (ROS) play an important role in the development of hypertension. Previous
      studies focusing on the role of vascular NADPH oxidases provided strong support
      of this concept. Although mitochondria represent one of the most significant
      sources of cellular ROS generation, the regulation of mitochondrial ROS
      generation in the cardiovascular system and its pathophysiological role in
      hypertension are much less understood. In this review, the role of mitochondrial
      oxidative stress in the pathophysiology of hypertension and cross talk between
      angiotensin II signaling, pathways involved in mechanotransduction, NADPH
      oxidases, and mitochondria-derived ROS are considered. The possible benefits of
      therapeutic strategies that have the potential to attenuate mitochondrial
      oxidative stress for the prevention/treatment of hypertension are also discussed.

PMID- 24043250
TI  - Fortilin reduces apoptosis in macrophages and promotes atherosclerosis.
AB  - Atherosclerosis, a deadly disease insufficiently addressed by cholesterol
      lowering drugs, needs new therapeutic strategies. Fortilin, a 172-amino acid
      multifunctional polypeptide, binds p53 and blocks its transcriptional activation
      of Bax, thereby exerting potent antiapoptotic activity. Although fortilin
      overexpressing mice reportedly exhibit hypertension and accelerated
      atherosclerosis, it remains unknown if fortilin, not hypertension, facilitates
      atherosclerosis. Our objective was to test the hypothesis that fortilin in and of
      itself facilitates atherosclerosis by protecting macrophages against apoptosis.
      We generated fortilin-deficient (fortilin(+/-)) mice and wild-type counterparts
      (fortilin(+/+)) on a LDL receptor (Ldlr)(-/-) apolipoprotein B mRNA editing
      enzyme, catalytic polypeptide 1 (Apobec1)(-/-) hypercholesterolemic genetic
      background, incubated them for 10 mo on a normal chow diet, and assessed the
      degree and extent of atherosclerosis. Despite similar blood pressure and lipid
      profiles, fortilin(+/-) mice exhibited significantly less atherosclerosis in
      their aortae than their fortilin(+/+) littermate controls. Quantitative
      immunostaining and flow cytometry analyses showed that the atherosclerotic
      lesions of fortilin(+/-) mice contained fewer macrophages than those of
      fortilin(+/+) mice. In addition, there were more apoptotic cells in the intima of
      fortilin(+/-) mice than in the intima of fortilin(+/+) mice. Furthermore,
      peritoneal macrophages from fortilin(+/-) mice expressed more Bax and underwent
      increased apoptosis, both at the baseline level and in response to oxidized LDL.
      Finally, hypercholesterolemic sera from Ldlr(-/-)Apobec1(-/-) mice induced
      fortilin in peritoneal macrophages more robustly than sera from control mice. In
      conclusion, fortilin, induced in the proatherosclerotic microenvironment in
      macrophages, protects macrophages against Bax-induced apoptosis, allows them to
      propagate, and accelerates atherosclerosis. Anti-fortilin therapy thus may
      represent a promising next generation antiatherosclerotic therapeutic strategy.

PMID- 24043251
TI  - Phosphatidylinositol 4,5-bisphosphate regulates CapZbeta1 and actin dynamics in
      response to mechanical strain.
AB  - Mechanical stress causes filament remodeling leading to myocyte hypertrophy and
      heart failure. The actin capping protein Z (CapZ) tightly binds to the barbed end
      of actin filaments, thus regulating actin assembly. The hypothesis is that the
      binding between CapZ and the actin filament is modulated through
      phosphatidylinositol 4,5-bisphosphate (PIP2) and how the COOH-terminus of
      CapZbeta1 regulates this binding. Primary neonatal rat ventricular myocytes
      (NRVMs) were strained at 10% amplitude and 1-Hz frequency. Dot blotting measured
      the PIP2 amount, and affinity precipitation assay assessed the direct interaction
      between PIP2 and CapZbeta1. Fluorescence recovery after photobleaching of green
      fluorescent protein-CapZbeta1 and actin-green fluorescent protein after 1 h of
      strain shows the dynamics significantly increased above the unstrained group. The
      increases in CapZ and actin dynamics were blunted by neomycin, suggesting PIP2
      signaling is involved. The amount of PIP2 dramatically increased in NRVMs
      strained for 1 h. With a ROCK or RhoA inhibitor, changes were markedly reduced.
      Subcellular fractionation and antibody localization showed PIP2 distributed to
      the sarcomeres. More PIP2-bound CapZbeta1 was found in strained NRVMs. Less PIP2
      bound to the CapZbeta1 with its COOH-terminus intact than in the COOH-terminal
      mutant of CapZbeta1, suggesting some inhibitory role for the COOH-terminus.
      Myocyte hypertrophy normally induced by 48 h of cyclic strain was blunted by
      dominant negative RhoA or neomycin. This suggests that after many hours of cyclic
      strain, a possible mechanism for cell hypertrophy is the accumulation of thin
      filament assembly triggered partially by the increased PIP2 level and its binding
      to CapZ.

PMID- 24043252
TI  - A1 adenosine receptor negatively modulates coronary reactive hyperemia via
      counteracting A2A-mediated H2O2 production and KATP opening in isolated mouse
      hearts.
AB  - We previously demonstrated that A2A, but not A2B, adenosine receptors (ARs)
      mediate coronary reactive hyperemia (RH), possibly by producing H2O2 and,
      subsequently, opening ATP-dependent K(+) (KATP) channels in coronary smooth
      muscle cells. In this study, A1 AR knockout (KO), A3 AR KO, and A1 and A3 AR
      double-KO (A1/A3 DKO) mice were used to investigate the roles and mechanisms of
      A1 and A3 ARs in modulation of coronary RH. Coronary flow of isolated hearts was
      measured using the Langendorff system. A1 KO and A1/A3 DKO, but not A3 KO, mice
      showed a higher flow debt repayment [~30% more than wild-type (WT) mice, P <
      0.05] following a 15-s occlusion. SCH-58261 (a selective A2A AR antagonist, 1
      MUM) eliminated the augmented RH, suggesting the involvement of enhanced A2A AR
      mediated signaling in A1 KO mice. In isolated coronary arteries,
      immunohistochemistry showed an upregulation of A2A AR (1.6 +/- 0.2 times that of
      WT mice, P < 0.05) and a higher magnitude of adenosine-induced H2O2 production in
      A1 KO mice (1.8 +/- 0.3 times that of WT mice, P < 0.05), which was blocked by
      SCH-58261. Catalase (2,500 U/ml) and glibenclamide (a KATP channel blocker, 5
      MUM), but not N(G)-nitro-l-arginine methyl ester, also abolished the enhanced RH
      in A1 KO mice. Our data suggest that A1, but not A3, AR counteracts the A2A AR
      mediated CF increase and that deletion of A1 AR results in upregulation of A2A AR
      and/or removal of the negative modulatory effect of A1 AR, thus leading to an
      enhanced A2A AR-mediated H2O2 production, KATP channel opening, and coronary
      vasodilation during RH. This is the first report implying that A1 AR has a role
      in coronary RH.

PMID- 24043253
TI  - Endothelium-derived hyperpolarizing factor contributes to hypoxia-induced
      skeletal muscle vasodilation in humans.
AB  - Systemic hypoxia causes skeletal muscle vasodilation, thereby preserving O2
      delivery to active tissues. Nitric oxide (NO), adenosine, and prostaglandins
      contribute to this vasodilation, but other factors may also play a role. We
      tested the hypothesis that regional inhibition of endothelium-derived
      hyperpolarizing factor with the cytochrome P-450 2C9 antagonist fluconazole,
      alone or combined with the NO synthase antagonist N(G)-monomethyl-L-arginine (L
      NMMA), attenuates hypoxia-induced vasodilation. We compared forearm blood flow
      (FBF) and skin blood flow before and during brachial artery infusion of
      fluconazole (0.3 mg/min; trial 1) or fluconazole + L-NMMA (50 mg over 10 min;
      trial 2) and during systemic hypoxia (10 min, arterial Po2 ~37 mmHg) in infused
      (experimental) and control forearms of 12 healthy humans. During normoxia,
      fluconazole and fluconazole + L-NMMA reduced (P < 0.05) forearm vascular
      conductance (FVC) by ~10% and ~18%, respectively. During hypoxia and fluconazole
      (trial 1), FVC increased by 1.76 +/- 0.37 and 0.95 +/- 0.35 units in control and
      experimental forearms, respectively (P < 0.05). During hypoxia and fluconazole +
      L-NMMA (trial 2), FVC increased by 2.32 +/- 0.51 and 0.72 +/- 0.22 units in
      control and experimental forearms, respectively (P < 0.05). Similarly, during
      hypoxia with L-NMMA alone (trial 3; n = 8) FVC increased by 1.51 +/- 0.46 and
      0.45 +/- 0.32 units in control and experimental forearms, respectively (P <
      0.05). These effects were not due to altered skin blood flow. We conclude that
      endothelium-derived hyperpolarizing factor contributes to basal vascular tone and
      to hypoxia-induced skeletal muscle vasodilation and could be particularly
      relevant when other vasodilator systems are impaired.

PMID- 24043254
TI  - Three-dimensional printing physiology laboratory technology.
AB  - Since its inception in 19th-century Germany, the physiology laboratory has been a
      complex and expensive research enterprise involving experts in various fields of
      science and engineering. Physiology research has been critically dependent on
      cutting-edge technological support of mechanical, electrical, optical, and more
      recently computer engineers. Evolution of modern experimental equipment is
      constrained by lack of direct communication between the physiological community
      and industry producing this equipment. Fortunately, recent advances in open
      source technologies, including three-dimensional printing, open source hardware
      and software, present an exciting opportunity to bring the design and development
      of research instrumentation to the end user, i.e., life scientists. Here we
      provide an overview on how to develop customized, cost-effective experimental
      equipment for physiology laboratories.

PMID- 24043255
TI  - Soluble epoxide hydrolase inhibitor trans-4-[4-(3-adamantan-1-yl-ureido)
      cyclohexyloxy]-benzoic acid is neuroprotective in rat model of ischemic stroke.
AB  - Soluble epoxide hydrolase (sEH) diminishes vasodilatory and neuroprotective
      effects of epoxyeicosatrienoic acids by hydrolyzing them to inactive dihydroxy
      metabolites. The primary goals of this study were to investigate the effects of
      acute sEH inhibition by trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]
      benzoic acid (t-AUCB) on infarct volume, functional outcome, and changes in
      cerebral blood flow (CBF) in a rat model of ischemic stroke. Focal cerebral
      ischemia was induced in rats for 90 min followed by reperfusion. At the end of 24
      h after reperfusion rats were euthanized for infarct volume assessment by
      triphenyltetrazolium chloride staining. Brain cortical sEH activity was assessed
      by ultra performance liquid chromatography-tandem mass spectrometry. Functional
      outcome at 24 and 48 h after reperfusion was evaluated by arm flexion and sticky
      tape tests. Changes in CBF were assessed by arterial spin-labeled-MRI at
      baseline, during ischemia, and at 180 min after reperfusion. Neuroprotective
      effects of t-AUCB were evaluated in primary rat neuronal cultures by Cytotox
      Flour kit and propidium iodide staining. t-AUCB significantly reduced cortical
      infarct volume by 35% (14.5 +/- 2.7% vs. 41.5 +/- 4.5%), elevated cumulative
      epoxyeicosatrienoic acids-to-dihydroxyeicosatrienoic acids ratio in brain cortex
      by twofold (4.40 +/- 1.89 vs. 1.97 +/- 0.85), and improved functional outcome in
      arm-flexion test (day 1: 3.28 +/- 0.5 s vs. 7.50 +/- 0.9 s; day 2: 1.71 +/- 0.4 s
      vs. 5.28 +/- 0.5 s) when compared with that of the vehicle-treated group. t-AUCB
      significantly reduced neuronal cell death in a dose-dependent manner (vehicle:
      70.9 +/- 7.1% vs. t-AUCB0.1MUM: 58 +/- 5.11% vs. t-AUCB0.5MUM: 39.9 +/- 5.8%).
      These findings suggest that t-AUCB may exert its neuroprotective effects by
      affecting multiple components of neurovascular unit including neurons,
      astrocytes, and microvascular flow.

PMID- 24043256
TI  - Impact of sex on the heart's metabolic and functional responses to diabetic
      therapies.
AB  - Increased myocardial lipid delivery is a determinant of myocardial substrate
      metabolism and function in animal models of type 2 diabetes (T2DM). Sex also has
      major effects on myocardial metabolism in the human heart. Our aims were to
      determine whether 1) sex affects the myocardial metabolic response to lipid
      lowering in T2DM, 2) altering lipid [fatty acid (FA) or triglyceride] delivery to
      the heart would lower the elevated myocardial lipid metabolism associated with
      T2DM, and 3) decreasing lipid delivery improves diastolic dysfunction in T2DM. To
      this end, we studied 78 T2DM patients (43 women) with positron emission
      tomography, echocardiography, and whole body tracer studies before and 3 mo after
      randomization to metformin (MET), metformin + rosiglitazone (ROSI), or metformin
      + Lovaza (LOV). No treatment main effects were found for myocardial substrate
      metabolism, partly because men and women often had different responses to a given
      treatment. In men, MET decreased FA clearance, which was linked to increased
      plasma FA levels, myocardial FA utilization and oxidation, and lower myocardial
      glucose utilization. In women, ROSI increased FA clearance, thereby decreasing
      plasma FA levels and myocardial FA utilization. Although LOV did not change
      triglyceride levels, it improved diastolic function, particularly in men. Group
      and sex also interacted in determining myocardial glucose uptake. Thus, in T2DM,
      different therapeutic regimens impact myocardial metabolism and diastolic
      function in a sex-specific manner. This suggests that sex should be taken into
      account when designing a patient's diabetes treatment. 

PMID- 24043257
TI  - A novel heart failure mice model of hypertensive heart disease by angiotensin II
      infusion, nephrectomy, and salt loading.
AB  - Although the mouse heart failure (HF) model of hypertensive heart disease (HHD)
      is useful to investigate the pathophysiology and new therapeutic targets for HHD,
      the model using simple experimental procedures and stable phenotypes has not been
      established. This study aimed to develop a novel mouse HF model of HHD by
      combining salt loading and uninephrectomy with ANG II infusion. Eight-week-old
      C57BL/6 male mice were treated with ANG II infusion (AT), ANG II infusion and
      uninephrectomy (AN), ANG II infusion and salt loading (AS), or ANG II infusion,
      uninephrectomy, and salt loading (ANS). Systolic blood pressure was significantly
      elevated and left ventricular (LV) hypertrophy was found in AT, AN, AS, and ANS
      mice, and there were no significant differences in those parameters between the
      four groups. At 6 wk after the procedures, only ANS mice showed significant
      decreases in LV fractional shortening and increases in lung weight with a high
      incidence. This phenotype was reproducible, and there were few perioperative or
      early deaths in the experimental procedures. Severe LV fibrosis was found in ANS
      mice. Oxidative stress was enhanced and small GTPase Rac1 activity was
      upregulated in the hearts of ANS mice. After the addition of salt loading and
      uninephrectomy to the ANG II infusion mouse model, cardiac function was
      significantly impaired, and mice developed HF. This might be a novel and useful
      mouse HF model to study the transition from compensated LV hypertrophy to HF in
      HHD.

PMID- 24043258
TI  - Cell matrix contact modifies endothelial major histocompatibility complex class
      II expression in high-glucose environment.
AB  - Atherosclerosis is a chronic inflammatory disease. Cardiovascular risk factors
      such as hyperglycemia, hyperlipidemia, and arterial hypertension induce
      endothelial dysfunction with alterations in endothelial biosecretion and immune
      behavior. The aim of this study is to elucidate whether glucose-induced
      modifications of endothelial biosecretory and immune functions are regulated by
      interactions of endothelial cells (ECs) with their extracellular matrix [ECs
      plated on polystyrene-coated tissue culture plates (TC-EC) vs. ECs embedded
      within three-dimensional (3-D) collagen-based matrixes (3D-EC)]. In the absence
      of glucose, IFN-gamma-induced phosphorylation of JAK and STAT proteins and human
      leukocyte antigen (HLA)-DR expression were lower in 3D-EC compared with TC-EC.
      Inversely, the expression of suppressor of cytokine signaling proteins (SOCS)-1
      and -3 were significantly higher in naive 3D-EC compared with naive TC-EC. IFN
      gamma-induced upregulation of SOCS proteins was further amplified by the 3-D
      environment. Glucose significantly augmented IFN-gamma-dependent signaling
      pathways in TC-EC. IFN-gamma-induced phosphorylation of JAK and STAT proteins as
      well as HLA-DR expression by ECs in low- and high-glucose medium was
      significantly lower in 3-D than in two-dimensional environment. Glucose increased
      SOCS expression in TC-EC and 3D-EC to the same extent, such that expression
      levels in 3D-EC exceeded SOCS-1 and -3 expression in TC-EC by 1.6-2.5-fold. In
      conclusion, low- and high-glucose concentrations amplify IFN-gamma-induced
      signaling pathways in TC-EC. Increased SOCS expression raises the threshold for
      IFN-gamma to induce HLA-DR expression in a 3-D environment. This immunoprotective
      effect is maintained even in states of experimental hyperglycemia.

PMID- 24043259
TI  - High interstitial fluid pressure promotes tumor cell proliferation and invasion
      in oral squamous cell carcinoma.
AB  - It has been shown that interstitial fluid pressure (IFP) is elevated in many
      solid tumors. The elevated IFP in tumors is responsible, at least in part, for
      the poor blood supply, inadequate delivery of therapeutic agents to solid tumors
      and poor treatment response in patients. The present study was carried out to
      examine alterations in malignant phenotypes in oral squamous cell carcinoma cells
      subjected to conditions mimicking IFP and to identify the relevant molecular
      mechanisms. We investigated tumor cell proliferation and invasion using SCC-4 and
      SCC-9 cells subjected to an increased extracellular pressure of 0, 15 and 30 mmHg
      in vitro. The results revealed that the increased IFP resulted in a marked
      increase in cancer cell proliferation, survival and invasion in vitro and altered
      the expression of >1,800 genes involved in invasion and metastasis, the heat
      shock pathway, the p38 and JNK signaling pathway, apoptosis and the cell growth
      and differentiation signaling pathway. These results suggest the important
      potential clinical application of measuring IFP, which can be used as a generic
      marker of prognosis and response to therapy.

PMID- 24043260
TI  - Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal
      pigment epithelium and reduces choroidal neovascularization.
AB  - Activation of Rap1 GTPase can improve the integrity of the barrier of the retina
      pigment epithelium (RPE) and reduce choroidal neovascularization (CNV).
      Inhibition of NADPH oxidase activation also reduces CNV. We hypothesize that Rap1
      inhibits NADPH oxidase-generated ROS and thereby reduces CNV formation. Using a
      murine model of laser-induced CNV, we determined that reduced Rap1 activity in
      RPE/choroid occurred with CNV formation and that activation of Rap1 by 2'-O-Me
      cAMP (8CPT)-reduced laser-induced CNV via inhibiting NADPH oxidase-generated ROS.
      In RPE, inhibition of Rap1 by Rap1 GTPase-activating protein (Rap1GAP) increased
      ROS generation, whereas activation of Rap1 by 8CPT reduced ROS by interfering
      with the assembly of NADPH oxidase membrane subunit p22phox with NOX4 or
      cytoplasmic subunit p47phox. Activation of NADPH oxidase with Rap1GAP reduced RPE
      barrier integrity via cadherin phosphorylation and facilitated choroidal EC
      migration across the RPE monolayer. Rap1GAP-induced ROS generation was inhibited
      by active Rap1a, but not Rap1b, and activation of Rap1a by 8CPT in Rap1b(-/-)
      mice reduced laser-induced CNV, in correlation with decreased ROS generation in
      RPE/choroid. These findings provide evidence that active Rap1 reduces CNV by
      interfering with the assembly of NADPH oxidase subunits and increasing the
      integrity of the RPE barrier.

PMID- 24043262
TI  - Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens
      reduces murine atherosclerosis.
AB  - Atherosclerosis is a lipid-driven inflammatory disease of the vessel wall,
      characterized by the chronic activation of macrophages. We investigated whether
      the helminth-derived antigens [soluble egg antigens (SEAs)] could modulate
      macrophage inflammatory responses and protect against atherosclerosis in mice. In
      bone marrow-derived macrophages, SEAs induce anti-inflammatory macrophages,
      typified by high levels of IL-10 and reduced secretion of proinflammatory
      mediators. In hyperlipidemic LDLR(-/-) mice, SEA treatment reduced plaque size by
      44%, and plaques were less advanced compared with PBS-injected littermate
      controls. The atheroprotective effect of SEAs was found to be mainly independent
      of cholesterol lowering and T-lymphocyte responses but instead could be
      attributed to diminished myeloid cell activation. SEAs reduced circulating
      neutrophils and inflammatory Ly6C(high) monocytes, and macrophages showed high IL
      10 production. In line with the observed systemic effects, atherosclerotic
      lesions of SEA-treated mice showed reduced intraplaque inflammation as
      inflammatory markers [TNF-alpha, monocyte chemotactic protein 1 (MCP-1),
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), and CD68], neutrophil content, and newly recruited macrophages were
      decreased. We show that SEA treatment protects against atherosclerosis
      development by dampening inflammatory responses. In the future, helminth-derived
      components may provide novel opportunities to treat chronic inflammatory
      diseases, as they diminish systemic inflammation and reduce the activation of
      immune cells.

PMID- 24043261
TI  - Modulation of taste responsiveness by the satiation hormone peptide YY.
AB  - It has been hypothesized that the peripheral taste system may be modulated in the
      context of an animal's metabolic state. One purported mechanism for this
      phenomenon is that circulating gastrointestinal peptides modulate the functioning
      of the peripheral gustatory system. Recent evidence suggests endocrine signaling
      in the oral cavity can influence food intake (FI) and satiety. We hypothesized
      that these hormones may be affecting FI by influencing taste perception. We used
      immunohistochemistry along with genetic knockout models and the specific
      reconstitution of peptide YY (PYY) in saliva using gene therapy protocols to
      identify a role for PYY signaling in taste. We show that PYY is expressed in
      subsets of taste cells in murine taste buds. We also show, using brief-access
      testing with PYY knockouts, that PYY signaling modulates responsiveness to bitter
      tasting stimuli, as well as to lipid emulsions. We show that salivary PYY
      augmentation, via viral vector therapy, rescues behavioral responsiveness to a
      lipid emulsion but not to bitter stimuli and that this response is likely
      mediated via activation of Y2 receptors localized apically in taste cells. Our
      findings suggest distinct functions for PYY produced locally in taste cells vs.
      that circulating systemically.

PMID- 24043263
TI  - Comment on Song et al.: associations between the major histocompatibility complex
      class I chain-related gene A transmembrane (MICA-TM) polymorphism and
      susceptibility to psoriasis and psoriatic arthritis: a meta-analysis.

PMID- 24043264
TI  - Conversion of glycerol to hydrogen rich gas.
AB  - Presently there is a glut of glycerol as the by-product of biofuel production and
      it will grow as production increases. The conundrum is how we can consume this
      material and convert it into a more useful product. One potential route is to
      reform glycerol to hydrogen rich gas including synthesis gas (CO + H2) and
      hydrogen. However, there is recent literature on various reforming techniques
      which may have a bearing on the efficiency of such a process. Hence in this
      review reforming of glycerol at room temperature (normally photo-catalytic),
      catalysis at moderate and high temperature and a non-catalytic pyrolysis process
      are presented. The high temperature processes allow the generation of synthesis
      gas with the hydrogen to carbon monoxide ratios being suitable for synthesis of
      dimethyl ether, methanol and for the Fischer-Tropsch process using established
      catalysts. Efficient conversion of synthesis gas to hydrogen involves additional
      catalysts that assist the water gas shift reaction, or involves in situ capture
      of carbon dioxide and hydrogen. Reforming at reduced temperatures including photo
      reforming offers the opportunity of producing synthesis gas or hydrogen using
      single catalysts. Together, these processes will assist in overcoming the
      worldwide glut of glycerol, increasing the competitiveness of the biofuel
      production and reducing our dependency on the fossil based, hydrogen rich gas. 

PMID- 24043265
TI  - Human papillomavirus in high-grade cervical lesions: Austrian data of a European
      multicentre study.
AB  - BACKGROUND: The purpose is to present the Austrian data of an observational,
      cross-sectional, multicentre study conducted in 13 European countries. This study
      was undertaken to assess human papillomavirus (HPV) type distribution in high
      grade cervical lesions. METHODS: Two hundred and ninety cases of high-grade
      cervical intraepithelial neoplasia (CIN2, CIN3) or adenocarcinoma in situ of the
      cervix from 2004 to 2007 were analysed by histopathological review and polymerase
      chain reaction for HPV. RESULTS: Two hundred and nine cases were "histologically
      eligible" and of those 206 were HPV+. Median age was 34 years (19-76 years). CIN3
      was the most frequent diagnosis (64.6 %), followed by CIN2/3 (19.4 %) and CIN2
      (13.6 %). Adenocarcinoma in situ was only detected together with a squamous
      lesion in 2.4 % cases. Majority of women (75.2 %) were infected with a single HPV
      type, 98.1 % of them with high-risk HPV types: HPV 16 (56.1 %), HPV 33 (12.3 %),
      HPV 31 (11.0 %), HPV 18 (3.9 %), HPV 35 (3.9 %), HPV 51 (3.2 %) and HPV 52 (2.6
      %), HPV 58 (1.9 %) and HPV 45 (0.6 %). The low-risk HPV 6 was found in 1.3 %
      cases. Forty-six lesions (22.3 %) contained multiple infections, 71.1 % of those
      were HPV 16 or 18 and 91.1 % were HPV 16, 18, 31, 33 or 45 positive. CONCLUSIONS:
      These Austrian data clearly demonstrate that HPV 16 is the predominant type in
      high-grade CIN, the immediate precursor lesions of cervical cancer. More than 60
      % of the lesions were associated with HPV 16 and 18 and more than 85 % with HPV
      16, 18, 31, 33 or 45. The prevalence of adenocarcinoma in situ is underestimated,
      since its detection is difficult with the current cytology screening.

PMID- 24043267
TI  - Reply to the comment of Ana I. Alvarez and Gracia Merino regarding "Assessment of
      ABCG2-mediated transport of xenobiotics across the blood-milk barrier of dairy
      animals using a new MDCKII in vitro model" by Wassermann et al. 2013.

PMID- 24043266
TI  - Short-term follow-up after laparoscopic versus conventional total mesorectal
      excision for low rectal cancer in a large teaching hospital.
AB  - PURPOSE: Laparoscopic resection for low rectal cancer remains controversial, and
      large randomized studies on oncologic outcome are lacking. The objective of this
      study was to analyze the short-term results of laparoscopic resection versus
      conventional total mesorectal excision (TME) for low rectal cancer (<=10 cm from
      the anal verge). METHODS: The institutional colorectal surgery database was
      reviewed, and 166 consecutive patients operated for low rectal cancer between
      2006 and 2011 were included in this analysis which focuses on the first 18 months
      of follow-up. RESULTS: Eighty patients underwent conventional TME, whereas 86
      patients underwent laparoscopic TME. Patient characteristics were comparable
      between groups. Conversion rate was 17 %. Laparoscopic rectal resection resulted
      in significantly less blood loss (200 versus 475 ml, p = <0.001) and a 3-day
      shorter hospital stay (median, 7 versus 10 days; p = 0.06). Oncologic results
      from resected specimens were comparable, although significantly more lymph nodes
      were harvested in laparoscopic resections (median, 13 versus 11; p = 0.005).
      Disease-free survival after curative resection was better in the laparoscopic
      group (p = 0.04), but this was no longer significant after correction for
      potential confounders. CONCLUSIONS: This analysis of short-term results of
      laparoscopic versus conventional TME for low rectal cancer demonstrates that
      laparoscopic surgery is feasible and safe, resulting in similar oncologic
      outcomes with less blood loss, a trend towards less postoperative complications
      and shorter duration of hospital stay. Further randomized studies are needed to
      attribute to the body of evidence of equivalence or even superiority of
      laparoscopic resections compared to conventional resections for distal rectal
      cancer.

PMID- 24043270
TI  - National burden of invasive methicillin-resistant Staphylococcus aureus
      infections, United States, 2011.
AB  - IMPORTANCE: Estimating the US burden of methicillin-resistant Staphylococcus
      aureus (MRSA) infections is important for planning and tracking success of
      prevention strategies. OBJECTIVE: To describe updated national estimates and
      characteristics of health care- and community-associated invasive methicillin
      resistant Staphylococcus aureus (MRSA) infections in 2011. DESIGN, SETTING, AND
      PARTICIPANTS: Active laboratory-based case finding identified MRSA cultures in 9
      US metropolitan areas from 2005 through 2011. Invasive infections (MRSA cultured
      from normally sterile body sites) were classified as health care-associated
      community-onset (HACO) infections (cultured <= 3 days after admission and/or
      prior year dialysis, hospitalization, surgery, long-term care residence, or
      central vascular catheter presence <= 2 days before culture); hospital-onset
      infections (cultured >3 days after admission); or community-associated infections
      if no other criteria were met. National estimates were adjusted using US census
      and US Renal Data System data. MAIN OUTCOMES AND MEASURES: National estimates of
      invasive HACO, hospital-onset, and community-associated MRSA infections using US
      census and US Renal Data System data as the denominator. RESULTS: An estimated
      80,461 (95% CI, 69,515-93,914) invasive MRSA infections occurred nationally in
      2011. Of these, 48,353 (95% CI, 40,195-58,642) were HACO infections; 14,156 (95%
      CI, 10,096-20,440) were hospital-onset infections; and 16,560 (95% CI, 12,806
      21,811) were community-associated infections. Since 2005, adjusted national
      estimated incidence rates decreased among HACO infections by 27.7% and hospital
      onset infections decreased by 54.2%; community-associated infections decreased by
      only 5.0%. Among recently hospitalized community-onset (nondialysis) infections,
      64% occurred 3 months or less after discharge, and 32% of these were admitted
      from long-term care facilities. CONCLUSIONS AND RELEVANCE: An estimated 30,800
      fewer invasive MRSA infections occurred in the United States in 2011 compared
      with 2005; in 2011 fewer infections occurred among patients during
      hospitalization than among persons in the community without recent health care
      exposures. Effective strategies for preventing infections outside acute care
      settings will have the greatest impact on further reducing invasive MRSA
      infections nationally.

PMID- 24043269
TI  - Identification of evidence-based interventions for promoting HIV medication
      adherence: findings from a systematic review of U.S.-based studies, 1996-2011.
AB  - A systematic review was conducted to identify evidence-based interventions (EBIs)
      for increasing HIV medication adherence behavior or decreasing HIV viral load
      among persons living with HIV (PLWH). We conducted automated searches of
      electronic databases (i.e., MEDLINE, EMBASE, PsycINFO, CINAHL) and manual
      searches of journals, reference lists, and listservs. Interventions were eligible
      for the review if they were U.S.-based, published between 1996 and 2011, intended
      to improve HIV medication adherence behaviors of PLWH, evaluated the intervention
      using a comparison group, and reported outcome data on adherence behaviors or HIV
      viral load. Each intervention was evaluated on the quality of study design,
      implementation, analysis, and strength of findings. Of the 65 eligible
      interventions, 10 are EBIs. The remaining 55 interventions failed to meet the
      efficacy criteria primarily due to null findings, small sample sizes, or low
      retention rates. Research gaps and future directions for development of adherence
      EBIs are discussed. 

PMID- 24043272
TI  - Profile: VAXIMM.

PMID- 24043271
TI  - Midkine is expressed and differentially processed during chronic obstructive
      pulmonary disease exacerbations and ventilator-associated pneumonia associated
      with Staphylococcus aureus infection.
AB  - Staphylococcus aureus is sometimes isolated from the airways during acute
      exacerbations of chronic obstructive pulmonary disease (COPD) but more commonly
      recognized as a cause of ventilator-associated pneumonia (VAP). Antimicrobial
      proteins, among them midkine (MK), are an important part of innate immunity in
      the airways. In this study, the levels and possible processing of MK in relation
      to S. aureus infection of the airways were investigated, comparing COPD and VAP,
      thus comparing a state of disease with preceding chronic inflammation and
      remodeling (COPD) with acute inflammation (that is, VAP). MK was detected in the
      small airways and alveoli of COPD lung tissue but less so in normal lung tissue.
      MK at below micromolar concentrations killed S. aureus in vitro. Proteolytic
      processing of MK by the staphylococcal metalloprotease aureolysin (AL), but not
      cysteine protease staphopain A (SA), resulted in impaired bactericidal activity.
      Degradation was seen foremost in the COOH-terminal portion of the molecule that
      harbors high bactericidal activity. In addition, MK was detected in sputum from
      patients suffering from VAP caused by S. aureus but less so in sputum from COPD
      exacerbations associated with the same bacterium. Recombinant MK was degraded
      more rapidly in sputum from the COPD patients than from the VAP patients and a
      greater proteolytic activity in COPD sputum was confirmed by zymography. Taken
      together, proteases of both bacteria and the host contribute to degradation of
      the antibacterial protein MK, resulting in an impaired defense of the airways, in
      particular, in COPD where the state of chronic inflammation could be of
      importance. 

PMID- 24043273
TI  - Haemolysis: the harbinger of recurrent mitral regurgitation after mitral valve
      repair.
AB  - We present a case of severe haemolysis post mitral valve repair that presented
      within the first week of operation. Despite assurance of a good repair, with
      initial postoperative echocardiographic evidence, the patient subsequently
      developed haemolysis and required forty units of blood over three months. We
      emphasize that an unexplained anaemia post mitral valve repair should trigger
      suspicion for mechanical haemolysis and suggest disease progression or failure of
      repair. 

PMID- 24043274
TI  - p190A RhoGAP is involved in EGFR pathways and promotes proliferation, invasion
      and migration in lung adenocarcinoma cells.
AB  - Overcoming acquired resistance to epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs) is an emerging issue in lung cancer treatment. We
      report evidence that a GTPase-activating protein, p190-A RhoGAP (p190), is a
      potential molecular target for the treatment of lung adenocarcinoma. We
      documented inhibition of phosphorylation of p190 by EGFR-TKI treatment in lung
      adenocarcinoma cell lines. Small interfering RNA-mediated knockdown of p190 leads
      lung adenocarcinoma cells to growth suppression and to inhibition of
      invasion/migration through inducing cell cycle arrest but not apoptosis. These
      findings were observed not only in EGFR-TKI-sensitive cells but also in EGFR-TKI
      resistant cells; even in cell lines harboring K-ras mutations. The mechanism of
      this inhibitory effect on growth and invasion/migration was Ras inactivation
      through disrupting the p190-A RhoGAP/p120RasGAP complex. In addition, a high
      level of p190 mRNA expression was observed in majority of surgically obtained
      tissue from lung adenocarcinoma patients. Overexpression of p190 mRNA associated
      with poor disease-free survival. The results suggest that overexpression of p190
      mRNA may be involved in the carcinogenesis of lung adenocarcinoma. These findings
      indicate that p190 is a possible molecular target for treatment of lung
      adenocarcinoma. 

PMID- 24043275
TI  - Bullied children and psychosomatic problems: a meta-analysis.
AB  - BACKGROUND AND OBJECTIVE: A previous meta-analysis showed that being bullied
      during childhood is related to psychosomatic problems, but many other studies
      have been published since then, including some longitudinal studies. We performed
      a new meta-analysis to quantify the association between peer victimization and
      psychosomatic complaints in the school-aged population. METHODS: We searched
      online databases up to April 2012, and bibliographies of retrieved studies and of
      narrative reviews, for studies that examined the association between being
      bullied and psychosomatic complaints in children and adolescents. The original
      search identified 119 nonduplicated studies, of which 30 satisfied the prestated
      inclusion criteria. RESULTS: Two separate random effects meta-analyses were
      performed on 6 longitudinal studies (odds ratio = 2.39, 95% confidence interval,
      1.76 to 3.24) and 24 cross-sectional studies (odds ratio = 2.17, 95% confidence
      interval, 1.91 to 2.46), respectively. Results showed that bullied children and
      adolescents have a significantly higher risk for psychosomatic problems than non
      bullied agemates. In the cross-sectional studies, the magnitude of effect size
      significantly decreased with the increase of the proportion of female
      participants in the study sample. No other moderators were statistically
      significant. CONCLUSIONS: The association between being bullied and psychosomatic
      problems was confirmed. Given that school bullying is a widespread phenomenon in
      many countries around the world, the present results indicate that bullying
      should be considered a significant international public health problem.

PMID- 24043276
TI  - Randomized trial of a population-based, home-delivered intervention for preschool
      language delay.
AB  - OBJECTIVE: Population approaches to lessen the adverse impacts of preschool
      language delay remain elusive. We aimed to determine whether systematic
      ascertainment of language delay at age 4 years, followed by a 10-month, 1-on-1
      intervention, improves language and related outcomes at age 5 years. METHODS: A
      randomized trial nested within a cross-sectional ascertainment of language delay.
      Children with expressive and/or receptive language scores more than 1.25 SD below
      the mean at age 4 years entered the trial. Children randomly allocated to the
      intervention received 18 1-hour home-based therapy sessions. The primary outcomes
      were receptive and expressive language (Clinical Evaluation of Language
      Fundamentals - Preschool, 2(nd) Edition) and secondary outcomes were child
      phonological skills, letter awareness, pragmatic skills, behavior, and quality of
      life. RESULTS: A total of 1464 children were assessed for language delay at age 4
      years. Of 266 eligible children, 200 (13.6%) entered the trial, with 91
      intervention (92% of 99) and 88 control (87% of 101) children retained at age 5
      years. At age 5 years, there was weak evidence of benefit to expressive (adjusted
      mean difference, intervention - control, 2.0; 95% confidence interval [CI] -0.5
      to 4.4; P = .12) but not receptive (0.6; 95% CI -2.5 to 3.8; P = .69) language.
      The intervention improved phonological awareness skills (5.0; 95% CI 2.2 to 7.8;
      P < .001) and letter knowledge (2.4; 95% CI 0.3 to 4.5; P = .03), but not other
      secondary outcomes. CONCLUSIONS: A standardized yet flexible 18-session language
      intervention was successfully delivered by non-specialist staff, found to be
      acceptable and feasible, and has the potential to improve long-term consequences
      of early language delay within a public health framework.

PMID- 24043277
TI  - Change in care among nonenrolled patients during and after a randomized trial.
AB  - OBJECTIVE: Parkland Memorial Hospital (PMH) participated in Surfactant, Positive
      Pressure, and Oxygenation Randomized Trial (SUPPORT), an unblinded controlled
      trial, in which preterm neonates of 24(0/7) to 27(6/7) weeks' gestational age
      (GA) were randomized in the delivery room (DR) to endotracheal intubation or
      nasal continuous positive airway pressure. We hypothesized that DR intubation
      could change in nonenrolled patients at PMH and that the change would be larger
      than in comparable centers not participating in the trial. METHODS: The PMH
      Cohort included eligible but nonenrolled neonates of 24(0/7) to 27(6/7) weeks
      (primary) and noneligible neonates of 28 to 34(6/7) weeks (confirmatory). A
      subset (24(0/7)-29(6/7)weeks) of that cohort was compared with a contemporaneous
      cohort born in centers participating in the Vermont Oxford Network (VON). We used
      a Poisson regression model to obtain adjusted relative risks (RRs) of DR
      intubation (during/after SUPPORT versus before SUPPORT) for PMH and for VON along
      with the ratio of these RRs. RESULTS: In the PMH cohort (n = 3527), the
      proportion of DR intubation decreased during/after SUPPORT in the lower GA group
      (adjusted RR 0.76, 95% confidence interval [CI] 0.59-0.96) and the upper GA group
      (adjusted RR 0.57, 95% CI 0.46-0.70). Compared with the RR for DR intubation in
      VON, the RR at PMH was smaller in the lower (ratio of RR 0.76, 95% CI 0.65-0.87)
      and the upper GA group (ratio of RR 0.52, 95% CI 0.39-0.68). CONCLUSIONS: A
      center's participation in an unblinded randomized trial may affect process of
      care of nonenrolled patients.

PMID- 24043278
TI  - Unproven therapies in clinical research and practice: the necessity to change the
      regulatory paradigm.

PMID- 24043279
TI  - Disparities in health insurance among children with same-sex parents.
AB  - OBJECTIVES: The objectives of this study were to examine disparities in health
      insurance coverage for children with same-sex parents and to investigate how
      statewide policies such as same-sex marriage and second-parent adoptions affect
      children's private insurance coverage. METHODS: We used data from the 2008-2010
      American Community Survey to identify children (aged 0-17 years) with same-sex
      parents (n = 5081), married opposite-sex parents (n = 1369789), and unmarried
      opposite-sex parents (n = 101678). We conducted multinomial logistic regression
      models to estimate the relationship between family type and type of health
      insurance coverage for all children and then stratified by each child's state
      policy environment. RESULTS: Although 77.5% of children with married opposite-sex
      parents had private health insurance, only 63.3% of children with dual fathers
      and 67.5% with dual mothers were covered by private health plans. Children with
      same-sex parents had fewer odds of private insurance after controlling for
      demographic characteristics but not to the extent of children with unmarried
      opposite-sex parents. Differences in private insurance diminished for children
      with dual mothers after stratifying children in states with legal same-sex
      marriage or civil unions. Living in a state that allowed second-parent adoptions
      also predicted narrower disparities in private insurance coverage for children
      with dual fathers or dual mothers. CONCLUSIONS: Disparities in private health
      insurance for children with same-sex parents diminish when they live in states
      that secure their legal relationship to both parents. This study provides
      supporting evidence in favor of recent policy statements by the American Academy
      of Pediatricians endorsing same-sex marriage and second-parent adoptions.

PMID- 24043280
TI  - Thyroid "vise" in an infant with neonatal Graves' disease.
AB  - On the rare occasion when neonatal goiter is the cause of airway compromise, it
      typically presents with a palpable neck mass. In the setting of maternal Graves'
      disease (GD), fetal and neonatal goiters are most commonly caused by maternal
      treatment with antithyroid medication, and the goiter resolves within days of
      initiation of thyroxine replacement in the neonate. We describe an atypical
      presentation of a patient with severe neonatal GD born to a euthyroid mother at
      35 weeks' gestational age with respiratory compromise, symptoms of
      hyperthyroidism, and a nonpalpable thyroid gland. The mother had a history of GD
      treated with radioactive iodine ablation; during the pregnancy she was treated
      with levothyroxine throughout and propylthiouracil beginning at 5 months'
      gestation, for fetal tachycardia. Laboratory testing after birth confirmed
      neonatal GD. The patient was treated with methimazole, Lugol's solution, and
      levothyroxine, and the patient remained euthyroid from day of life 10. After
      multiple extubation attempts failed, the patient was found on visualization
      studies to have a large, predominantly posterior, "vise-like" goiter encasing the
      larynx and upper trachea. The patient was successfully extubated, and all
      medications were discontinued on day of life 60. The patient remained euthyroid 1
      month after discontinuation of treatment. The patient's atypical presentation
      illustrates the need for early neck imaging in patients with neonatal GD and
      respiratory distress, especially when the thyroid gland is not palpable.
      Treatment options for resolving a goiter due to neonatal GD are not clear. 

PMID- 24043281
TI  - Trends in physical activity, sedentary behavior, diet, and BMI among US
      adolescents, 2001-2009.
AB  - OBJECTIVE: The high prevalence of adolescent obesity in the United States has
      been attributed to population changes in physical activity (PA), sedentary
      behaviors, and dietary behaviors. This study examines 8-year trends in these
      behaviors in US adolescents ages 11 to 16. METHODS: Nationally representative
      samples of US students in grades 6 to 10 were recruited during the 2001-2002 (N =
      14607), 2005-2006 (N = 9150), and 2009-2010 (N = 10848) school years by using
      multistage stratified designs, with census regions and grades as strata, and
      school districts as the primary sampling units. African-American and Hispanic
      students were oversampled to obtain better estimates for those groups. Using the
      Health Behavior in School-aged Children quadrennial surveys, identical questions
      assessed BMI, PA, and sedentary and dietary behaviors at each school year.
      Logistic and linear regression analyses were conducted taking into account the
      sampling design and controlling for age, gender, race/ethnicity, and family
      affluence. RESULTS: Across the quadrennial surveys, significant increases were
      identified in number of days with at least 60 minutes of PA, daily consumption of
      fruits and vegetables, eating breakfast on weekdays and weekends, and BMI.
      Television viewing and consumption of sweets and sweetened beverages decreased
      across this same period. These same patterns were seen in all racial/ethnic
      groups. CONCLUSIONS: These patterns suggest that public health efforts to improve
      the obesity-related behaviors of US adolescents may be having some success.
      However, alternative explanations for the increase in BMI over the same period
      need to be considered.

PMID- 24043283
TI  - Oral dexamethasone for bronchiolitis: a randomized trial.
AB  - OBJECTIVE: Determine whether dexamethasone treatment added to salbutamol reduces
      time to readiness for discharge in patients with bronchiolitis and possible
      asthma. METHODS: We compared efficacy and safety of dexamethasone, 1 mg/kg, then
      0.6 mg/kg for 4 more days, with placebo for acute bronchiolitis in patients with
      asthma risk, as determined by eczema or a family history of asthma in a first
      degree relative. All patients received inhaled salbutamol. Time to readiness for
      discharge was the primary efficacy outcome. RESULTS: Two hundred previously
      healthy infants diagnosed with bronchiolitis, median age 3.5 months, were
      enrolled. Five placebo recipients needed admission to intensive care unit during
      infirmary treatment (P = .02). Among 100 dexamethasone recipients, geometric mean
      time to readiness for discharge was 18.6 hours (95% confidence interval [CI],
      14.9 to 23.1 hours); among 90 control patients, 27.1 hours (95% CI, 21.8 to 33.8
      hours). The ratio, 0.69 (95% CI, 0.51 to 0.93), revealed a mean 31% shortening of
      duration to readiness for discharge favoring dexamethasone (P = .015). Twenty-two
      dexamethasone and 19 control patients were readmitted to the short stay infirmary
      in the week after discharge (P = .9). No hospitalizations or side effects were
      reported during 7 days of surveillance. CONCLUSIONS: Dexamethasone with
      salbutamol shortened time to readiness for infirmary discharge during
      bronchiolitis episodes in patients with eczema or a family history of asthma in a
      first-degree relative. Infirmary and clinic visits in the subsequent week
      occurred similarly for the 2 groups.

PMID- 24043284
TI  - Treatment outcomes of infants with cyanotic congenital heart disease treated with
      synbiotics.
AB  - OBJECTIVES: The goal was to investigate the effect of orally administered
      synbiotics on outcome of infants with cyanotic congenital heart disease (CCHD).
      METHODS: A prospective, blinded, randomized controlled trial was conducted to
      evaluate the effect of synbiotics on outcome of infants with CCHD. The infants
      with CCHD were assigned randomly to 2 groups. Infants in the study group were
      given synbiotic (Bifidobacterium lactis plus inulin) added to breast milk or
      mixed feeding until discharge or death. Infants in the placebo group were fed
      with breast milk or mixed feeding. The outcome measurements were nosocomial
      sepsis, necrotizing enterocolitis (NEC; Bell stage >= 2), length of NICU stay,
      and death. RESULTS: A total of 100 infants were enrolled in the trial: 50 in each
      arm. There were 9 cases of culture-proven sepsis (18%) in the placebo group and 2
      cases (4%) in the synbiotic group (P = .03). Length of NICU stay did not differ
      between the groups (26 [14-36] vs 32 days [20-44], P = .07]. There were 5 cases
      of NEC (10%) in the placebo group and none in the synbiotic group (P = .03). The
      incidence of death was lower in synbiotic group (5 [10%] of 50 vs 14 [28.0%] of
      50, respectively; P = .04). CONCLUSIONS: Synbiotics administered enterally to
      infants with CCHD might reduce the incidence of nosocomial sepsis, NEC, and
      death.

PMID- 24043282
TI  - Evidence for the management of adolescent depression.
AB  - Adolescent depression is a prevalent and disabling condition resulting in
      emotional suffering and social and educational dysfunction. Care for adolescent
      depression is suboptimal and could be improved through the development and use of
      quality indicators (QIs). This article reports on the development of a care
      pathway and QIs for the primary and specialty care management of adolescent
      depression from case identification through symptom remission. It presents
      evidence from a review of adolescent clinical practice guidelines and research
      literature to support QIs at critical nodes in the pathway, and describes
      implications for practice based on existing evidence. Barriers to measure
      development are identified, including gaps in empirical evidence, and a research
      agenda is suggested. 

PMID- 24043285
TI  - Improving delivery room management for very preterm infants.
AB  - BACKGROUND AND OBJECTIVES: Events in the delivery room significantly impact the
      outcomes of preterm infants. We developed evidence-based guidelines to prevent
      heat loss, reduce exposure to supplemental oxygen, and increase use of
      noninvasive respiratory support to improve the care and outcomes of infants with
      birth weight <=1250 g at our institution. METHODS: The guidelines were
      implemented through multidisciplinary conferences, routine use of a checklist,
      appointment of a dedicated resuscitation nurse, and frequent feedback to
      clinicians. This cohort study compares a historical group (n = 80) to a
      prospective group (n = 80, after guidelines were implemented). Primary outcome
      was axillary temperature at admission to the intensive care nursery. Secondary
      outcomes measured adherence to the guidelines and changes in clinically relevant
      patient outcomes. RESULTS: Baseline characteristics of the groups were similar.
      After introduction of the guidelines, average admission temperatures increased
      (36.4 degrees C vs 36.7 degrees C, P < .001) and the proportion of infants
      admitted with moderate/severe hypothermia fell (14% vs 1%, P = .003). Infants
      were exposed to less oxygen during the first 10 minutes (P < .001), with similar
      oxygen saturations. Although more patients were tried on continuous positive
      airway pressure (40% vs 61%, P = .007), the intubation rate was not significantly
      different (64% vs 54%, P = .20). Median durations of invasive ventilation and
      hospitalization decreased after the quality initiative (5 vs 1 days [P = .008]
      and 80 vs 60 days [P = .02], respectively). CONCLUSIONS: We have demonstrated
      significantly improved quality of delivery room care for very preterm infants
      after introduction of evidence-based delivery room guidelines. Multidisciplinary
      involvement and continuous education and reinforcement of the guidelines
      permitted sustained change.

PMID- 24043286
TI  - Mutation of FAS, XIAP, and UNC13D genes in a patient with a complex
      lymphoproliferative phenotype.
AB  - This article presents a case report for a child presenting with mixed clinical
      features of autoimmune lymphoproliferative syndrome (ALPS), familial
      hemophagocytic lymphohistiocytosis (FHL), and X-linked lymphoproliferative (XLP)
      disease. From 6 months, he exhibited splenomegaly and lymphoadenopathy and from 4
      years, he showed recurrent severe autoimmune hemocytopenia and sepsislike bouts
      of fever, from which he eventually died at the age of 12. Intriguingly, the
      patient carried mutations in FAS, XIAP, and UNC13D genes, which are involved in
      ALPS, XLP disease, and FHL, respectively. These mutations were inherited from the
      mother, who had rheumatoid arthritis but no signs of ALPS. A role for other
      modifying genes was suggested by the finding that the healthy father exhibited
      defective Fas function, without mutation of the FAS gene, and had transmitted to
      the patient an osteopontin (OPN) gene variant previously associated with ALPS.
      Therefore, several genes might influence the disease outcome in this family. In
      vitro analyses revealed that the FAS and the XIAP mutations decreased expression
      of the corresponding proteins, and the UNC13D mutation decreased granule
      secretion and Munc interaction with Rab-27a. These findings suggest that overlap
      may exist between ALPS, FHL, and XLP disease, in accordance with the notion that
      FHL and XLP disease are due to defective natural killer (NK)/NK T-cell function,
      which involves Fas. Therefore, we propose that NK cell defects should be
      evaluated in patients with ALPS-like characteristics, and hematopoietic stem cell
      transplantation should be considered in individuals with severe refractory
      cytopenia and FHL-like manifestations. 

PMID- 24043288
TI  - Cyclodextrin stabilised emulsions and cyclodextrinosomes.
AB  - We report the preparation of o/w emulsions stabilised by microcrystals of
      cyclodextrin-oil inclusion complexes. The inclusion complexes are formed by
      threading cyclodextrins from the aqueous phase on n-tetradecane or silicone oil
      molecules from the emulsion drop surface which grow further into microrods and
      microplatelets depending on the type of cyclodextrin (CD) used. These
      microcrystals remain attached on the surface of the emulsion drops and form
      densely packed layers which resemble Pickering emulsions. The novelty of this
      emulsion stabilisation mechanism is that molecularly dissolved cyclodextrin from
      the continuous aqueous phase is assembled into colloid particles directly onto
      the emulsion drop surface, i.e. molecular adsorption leads to effective Pickering
      stabilisation. The beta-CD stabilised tetradecane-in-water emulsions were so
      stable that we used this system as a template for preparation of
      cyclodextrinosomes. These structures were produced solely through formation of
      cyclodextrin-oil inclusion complexes and their assembly into a crystalline phase
      on the drop surface retained its stability after the removal of the core oil. The
      structures of CD-stabilised tetradecane-in-water emulsions were characterised
      using optical microscopy, fluorescence microscopy, cross-polarised light
      microscopy and WETSEM while the cyclodextrinosomes were characterised by SEM. We
      also report the preparation of CD-stabilised emulsions with a range of other
      oils, including tricaprylin, silicone oil, isopropyl myristate and sunflower oil.
      We studied the effect of the salt concentration in the aqueous phase, the type of
      CD and the oil volume fraction on the type of emulsion formed. The CD-stabilised
      emulsions can be applied in a range of surfactant-free formulations with possible
      applications in cosmetics, home and personal care. Cyclodextrinosomes could find
      applications in pharmaceutical formulations as microencapsulation and drug
      delivery vehicles. 

PMID- 24043287
TI  - Changes in plasma kynurenic acid concentration in septic shock patients
      undergoing continuous veno-venous haemofiltration.
AB  - Kynurenic acid (KYNA) is one of the end products of tryptophan metabolism. The
      aim of this study was to analyse plasma KYNA concentration in septic shock
      patients (SSP) with acute kidney injury (AKI) undergoing continuous veno-venous
      haemofiltration (CVVH). Changes in KYNA content were compared to alterations in
      the levels of procalcitonin (PCT), C-reactive protein and lactate. Adult SSP with
      AKI were examined. Measurements were conducted at seven time points: before
      beginning CVVH and at 6, 12, 24, 48, 72 and 96 h after the beginning of CVVH.
      Based on clinical outcomes, the data were analysed separately for survivors and
      non-survivors. Twenty-seven patients were studied. CVVH was associated with
      reduced plasma KYNA concentration only in survivors. Plasma KYNA concentration
      correlated with the levels of lactate and PCT only in survivors. (1) CVVH reduced
      plasma KYNA concentration only in survivors; (2) lack of this reduction may
      predict fatal outcomes in SSP.

PMID- 24043289
TI  - Bone health issues in breast cancer survivors: a Medicare Current Beneficiary
      Survey (MCBS) study.
AB  - PURPOSE: Breast cancer treatments (chemotherapy and hormone therapy) can cause a
      rapid loss in bone mineral density, leading to osteoporosis and fractures later
      in life. Fortunately, preventative measures (vitamin D, exercise, etc.) can delay
      bone loss if employed early enough. This study compares the prevalence of
      osteoporosis and osteoporosis-related discussions with physicians among female
      breast cancer survivors and females with no cancer history to determine if breast
      cancer patients are being correctly advised on their high risk of bone loss.
      METHODS: The 2003 Medicare Current Beneficiary Survey, a nationally
      representative sample of 550 women with a breast cancer history and 6,673 women
      with no cancer history aged >=65, was used. The first set of dependent variables
      collected information on bone health (osteoporosis, falls, and fractures). The
      second set of dependent variables collected information on bone health
      discussions with their physician. Multivariate logistic regression models were
      used to evaluate whether breast cancer was independently associated with bone
      health issues. RESULTS: After adjustment for confounders, a breast cancer
      diagnosis was found to be associated with a higher prevalence of an osteoporosis
      diagnosis over their lifetime (adjusted odds ratio (OR(adj)) = 1.32, 95 %
      confidence interval (95 % CI) = 1.08-1.61) and falls in the previous year
      (OR(adj) = 1.23, 95 % CI = 1.01-1.51) compared to respondents without a cancer
      diagnosis. However, breast cancer respondents were not more likely than
      respondents without a cancer diagnosis to discuss osteoporosis with their
      physician (OR(adj) = 1.20, 95 % CI = 0.96-1.50) or be told they are at high risk
      for osteoporosis (OR(adj) = 1.41, 95 % CI = 0.95-2.10). CONCLUSIONS: A breast
      cancer diagnosis was associated with an increased prevalence of osteoporosis and
      falls. Nevertheless, breast cancer respondents were not more likely to discuss
      osteoporosis with their physician nor were they more likely to be considered high
      risk for osteoporosis. Increased dialogue between physician and breast cancer
      patient pertaining to bone loss is needed.

PMID- 24043290
TI  - Agreement between telerehabilitation involving caregivers and face-to-face
      clinical assessment of lymphedema in breast cancer survivors.
AB  - Lymphedema is a lifetime complication of breast cancer survivors that can limit
      their participation in recreational or strenuous daily activities. Follow-up of
      lymphedema using an Internet application could help patients to determine the
      influence on their condition of these activities and adapt them accordingly. We
      aimed to determine the level of agreement between lymphedema assessment by
      telerehabilitation and by the traditional face-to-face method. Thirty breast
      cancer survivors participated in a descriptive study of repeated measures using a
      crossover design. Patients attended a session for clinical face-to-face and real
      time online telerehabilitation assessments of lymphedema. There was a 120-min
      interval between these two sessions. The order of sessions was randomly selected
      for each patient. A caregiver (relative or friend) conducted the
      telerehabilitation assessment using a system that includes a specific tool based
      on an arm diagram for measuring the participant's arm circumferences via a
      telehealth application. All outcome measures showed reliability estimates (alpha)
      >= 0.90; the lowest reliability was obtained for the total volume on the non
      affected side (alpha = 0.90). The diagnosis of lymphedema by the two methods also
      showed good inter-rater reliability (Rho = 0.89). These preliminary findings
      support the use of an Internet-based system to assess lymphedema in breast cancer
      survivors, offering carers a useful role in helping patients to follow up this
      lifetime health problem. 

PMID- 24043291
TI  - Stimulatory effect of nobiletin, a citrus polymethoxy flavone, on catecholamine
      synthesis through Ser19 and Ser40 phosphorylation of tyrosine hydroxylase in
      cultured bovine adrenal medullary cells.
AB  - We previously reported the dual effects of nobiletin, a compound of polymethoxy
      flavones found in citrus fruits, on catecholamine secretion in cultured bovine
      adrenal medullary cells. Here, we report the effects of nobiletin on
      catecholamine synthesis in the cells. Nobiletin increased the synthesis of (14)C
      catecholamines from [(14)C]tyrosine in a time (20-30 min)- and concentration (1.0
      100 MUM)-dependent manner. Nobiletin (10-100 MUM) also activated tyrosine
      hydroxylase activity. The stimulatory effect of nobiletin on (14)C-catecholamine
      synthesis was not observed when extracellular Ca(2+) was not present in the
      incubation medium. Protein kinase inhibitors including H-89, an inhibitor of
      cyclic AMP-dependent protein kinase, and KN-93, an inhibitor of Ca(2+)/calmodulin
      dependent protein kinase II, suppressed the stimulatory effects of nobiletin on
      catecholamine synthesis as well as tyrosine hydroxylase activity. Nobiletin also
      induced the phosphorylation of tyrosine hydroxylase at Ser(19) and Ser(40).
      Nobiletin (1.0-100 MUM) inhibited (14)C-catecholamine synthesis induced by
      acetylcholine. The present findings suggest that nobiletin, by itself, stimulates
      catecholamine synthesis through tyrosine hydroxylase phosphorylation at Ser(19)
      and Ser(40), whereas it inhibits catecholamine synthesis induced by acetylcholine
      in bovine adrenal medulla. 

PMID- 24043292
TI  - African-American breast cancer survivors' preferences for various types of
      physical activity interventions: a Sisters Network Inc. web-based survey.
AB  - BACKGROUND: Needs assessments are essential to developing lifestyle interventions
      for minority populations. To our knowledge, no physical activity (PA) needs
      assessment studies have been conducted for African-American (AA) breast cancer
      survivors. The purpose of this study was to determine the PA intervention
      preferences of AA breast cancer survivors and determine whether these preferences
      differ according to medical and sociodemographic factors. METHODS: AA breast
      cancer survivors (n = 475, mean age = 54 years) were recruited using ads sent via
      email and social media sites. Preferences for the mode of intervention delivery
      were assessed via web-based questionnaires. Descriptive statistics were used to
      characterize their interests in PA interventions, and subgroup differences were
      assessed. RESULTS: About 49 % (142 out of 291) of the participants who completed
      the survey were obese and 54 % did not meet the recommended guidelines for PA.
      Most (90 %) participants reported that they could participate in PA, and many (67
      %) indicated that they were interested in receiving program materials.
      Participants expressed the greatest interest in email (50 %)-, web (48 %)-, or
      mail-based (45 %) over group (39 %), and telephone (10 %). Women also expressed
      the greatest interest in participating in studies that promoted walking and
      resistance or strength training. Intervention preferences did not differ
      significantly (P > 0.05) across sociodemographic or medical factors. CONCLUSION:
      Most AA breast cancer survivors can participate in PA, and many are interested in
      interventions that promoted walking and resistance training and were delivered
      via the email or web. The development of culturally sensitive interventions that
      provide activities consistent with preferences can assist AA breast cancer
      survivors to adopt and maintain a healthy lifestyle. IMPLICATIONS FOR CANCER
      SURVIVORS: Despite evidence that AA breast cancer survivors are at increased risk
      for poor breast cancer-specific outcomes, they are underrepresented in clinical
      trials promoting positive health behaviors. In this study, we propose to assess
      their exercise preferences and receptivity to a culturally appropriate PA
      intervention developed in collaboration with the Sisters Network Inc. Health
      promotion programs developed in collaboration with a community-based organization
      may aid in the development of research tools and resources that AA breast cancer
      survivors are receptive to using.

PMID- 24043293
TI  - The roles of cis- and trans-regulation in the evolution of regulatory
      incompatibilities and sexually dimorphic gene expression.
AB  - Evolutionary changes in gene expression underlie many aspects of phenotypic
      diversity within and among species. Understanding the genetic basis for evolved
      changes in gene expression is therefore an important component of a comprehensive
      understanding of the genetic basis of phenotypic evolution. Using interspecific
      introgression hybrids, we examined the genetic basis for divergence in genome
      wide patterns of gene expression between Drosophila simulans and Drosophila
      mauritiana. We find that cis-regulatory and trans-regulatory divergences differ
      significantly in patterns of genetic architecture and evolution. The effects of
      cis-regulatory divergence are approximately additive in heterozygotes,
      quantitatively different between males and females, and well predicted by
      expression differences between the two parental species. In contrast, the effects
      of trans-regulatory divergence are associated with largely dominant introgressed
      alleles, have similar effects in the two sexes, and generate expression levels in
      hybrids outside the range of expression in both parental species. Although the
      effects of introgressed trans-regulatory alleles are similar in males and
      females, expression levels of the genes they regulate are sexually dimorphic
      between the parental D. simulans and D. mauritiana strains, suggesting that pure
      species genotypes carry unlinked modifier alleles that increase sexual dimorphism
      in expression. Our results suggest that independent effects of cis-regulatory
      substitutions in males and females may favor their role in the evolution of
      sexually dimorphic phenotypes, and that trans-regulatory divergence is an
      important source of regulatory incompatibilities. 

PMID- 24043294
TI  - Fucosylated multiwalled carbon nanotubes for Kupffer cells targeting for the
      treatment of cytokine-induced liver damage.
AB  - PURPOSE: To develop, characterize and exploring the sulfasalazine loaded
      fucoyslated multi walled carbon nanotubes for Kupffer cell targeting for
      effective management of cytokine-induce liver damage. METHODS: Sulfasalazine was
      loaded into the fucosylated MWCNTs after subsequential functionalization
      (carboxylation, acylation and amidation) using dialysis membrane technique. The
      in vitro, in vivo studies were performed on macrophages J 774 cell line for
      Kupffer cells targeting for the treatment of cytokine-induced liver damage.
      RESULTS: The loading of SSZ into SSZ-FUCO-MWCNTs was 87.77 +/- 0.11% (n = 3).
      Sustained release was obtained from SSZ-FUCO-MWCNTs, with 89.12 +/- 0.71% of SSZ
      released into medium at 48th hr. SSZ-FUCO-MWCNTs showed the 9.0  +/- 0.23%
      hemolysis was drastically reduced from 21.62 +/- 0.24% SSZMWCNTs 21.62 +/- 0.24%.
      In SRB assay, SSZ-FUCO-MWCNTs showed more cytotoxicity than raw and SSZ-MWCNTs.
      In cytokine assay, SSZ- FUCO-MWCNTs exhibited significantly higher inhibition of
      IL-12 p40 secretion. In Western blot assay, SSZ-FUCO-MWCNTs significantly inhibit
      NF-kappaB activation. CONCLUSION: The results suggested that the SSZ-FUCO-MWCNTs
      may be useful nano-carriers for targeted delivery to Kupffer cells in the
      treatment of cytokine-induced liver damage.

PMID- 24043295
TI  - Tumor-specific delivery and therapy by double-targeted DTX-CMCS-PEG-NGR
      conjugates.
AB  - PURPOSE: To synthesize and evaluate the antitumor efficacy of double-targeted
      docetaxel (DTX)-carboxymethyl chitosan (CMCS)-PEG-NGR (DTX-CPN) conjugates that
      could target to CD13 over-expressed tumor neovascular endothelium cells and tumor
      cells. METHODS: DTX was conjugated to CMCS via biodegradable linker and cNGR was
      applied to endow the conjugates with double targeting ability. The physiochemical
      properties and stability of this DTX-CPN conjugates were characterized. Cellular
      uptake study was carried out to evaluate the targeting ability of DTX-CPN
      conjugates. Cytotoxicity and apoptosis analysis were conducted to evaluate in
      vitro antitumor effects. In vivo antitumor efficacy was investigated in B16
      murine melanoma model. RESULTS: DTX-CPN conjugates could self-assemble into
      nanoparticles in water and were stable in plasma. cNGR modification could promote
      the cellular uptake of DTX-CPN conjugates in CD13 positive HUVEC and B16 cells,
      leading to more significant cytotoxicity and apoptosis effect than non-targeted
      conjugates. DTX-CPN conjugates also exhibited better antitumor effect than non
      targeted conjugates and Duopafei(r) in a B16 murine melanoma model. CONCLUSIONS:
      Double-targeted DTX-CPN conjugates could efficiently target to tumor neovascular
      cells and tumor cells, and achieve good antitumor effects. DTX-CPN conjugates may
      be promising candidate for one-double targeting cancer therapy.

PMID- 24043296
TI  - [New aspects of the pathogenesis, clinical symptoms and management of psoriatic
      arthropathy].

PMID- 24043297
TI  - [Therapy of psoriatic arthritis].
AB  - In psoriatic arthritis (PsA) the heterogeneous spectrum of the disease with
      arthritis/synovitis, axial manifestation, enthesitis, dactylitis, psoriatic skin
      disease and nail psoriasis has to be considered. Moreover, PsA activity and
      severity as well as comorbidities are of importance for making therapeutic
      decisions. Measurement instruments developed for therapeutic studies of
      rheumatoid arthritis or ankylosing spondylitis are often not appropriate for
      application in PsA investigations. In this paper established therapies with
      nonsteroidal antirheumatic drugs, disease modifying antirheumatic drugs (DMARDs)
      and TNF-alpha inhibitors and the current EULAR guidelines from 2012 are reviewed.
      However, there is a need for new therapeutic agents for those patients who do not
      respond to or do not tolerate the current therapies. Other biologic agents have
      also been tested for PsA with moderate effects only. New therapeutic options
      could result from the anti-IL12 and anti-IL23 receptor monoclonal antibody
      ustekinumab and from small molecules such as the oral PDE-4 inhibitor apremilast.

PMID- 24043298
TI  - [Anti-interferon alpha therapy of systemic lupus erythematosus].

PMID- 24043299
TI  - C-reactive protein, but not low-density lipoprotein cholesterol levels, associate
      with coronary atheroma regression and cardiovascular events after maximally
      intensive statin therapy.
AB  - BACKGROUND: Baseline C-reactive protein (CRP) levels predict major adverse
      cardiovascular events (MACE: death, myocardial infarction, stroke, coronary
      revascularization, and hospitalization for unstable angina). The association
      between changes in CRP levels with plaque progression and MACE in the setting of
      maximally intensive statin therapy is unknown. METHODS AND RESULTS: The Study of
      Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus
      Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary
      atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg
      for 24 months. The treatment groups did not differ significantly in the change
      from baseline of percent atheroma volume on intravascular ultrasound, CRP
      modulating effects, or MACE rates, thus allowing for a (prespecified) post hoc
      analysis to test associations between the changes in CRP levels with coronary
      disease progression and MACE. Patients with nonincreasing CRP levels (n=621) had
      higher baseline (2.3 [1.1-4.7] versus 1.1 [0.5-1.8] mg/L; P<0.001) and lower
      follow-up CRP levels (0.8 [0.5-1.7] versus 1.6 [0.7-4.1] mg/L; P<0.001) versus
      those with increasing CRP levels (n=364). Multivariable analysis revealed a
      nonincreasing CRP level to independently associate with greater percent atheroma
      volume regression (P=0.01). Although the (log) change in CRP did not associate
      with MACE (hazard ratio, 1.18; 95% confidence interval, 0.93-1.50; P=0.17), the
      (log) on-treatment CRP associated significantly with MACE (hazard ratio, 1.28;
      95% confidence interval, 1.04-1.56; P=0.02). On-treatment low-density lipoprotein
      cholesterol levels did not correlate with MACE (hazard ratio, 1.09; 95%
      confidence interval, 0.88-1.35; P=0.45). CONCLUSIONS: Following 24 months of
      potent statin therapy, on-treatment CRP levels associated with MACE. Inflammation
      may be an important driver of residual cardiovascular risk in patients with
      coronary artery disease despite aggressive statin therapy. CLINICAL TRIAL
      REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT000620542.

PMID- 24043301
TI  - Variable impact of state legislative advocacy on registry participation and
      regional systems of care implementation: a policy statement from the American
      Heart Association.

PMID- 24043302
TI  - Use of remote monitoring of newly implanted cardioverter-defibrillators: insights
      from the patient related determinants of ICD remote monitoring (PREDICT RM)
      study.
AB  - BACKGROUND: Current guidelines recommend using remote patient monitoring (RPM)
      for implantable cardioverter-defibrillators, but the patterns of adoption of this
      technology have not been described. Successful use of RPM depends on (1) the
      enrollment of the patient into an RPM system and (2) subsequent activation of RPM
      by the enrolled patient. We examined RPM enrollment and activation rates and the
      patient, physician, and institutional determinants of RPM use. METHODS AND
      RESULTS: Information about the use of RPM-capable devices was obtained from the
      Boston Scientific Corporation ALTITUDE program and linked to the National
      Cardiovascular Data Registry ICD Registry. Patients were first categorized as RPM
      enrolled and RPM-not enrolled, and the RPM-enrolled patients were further
      categorized into RPM-active and RPM-inactive groups based on whether they
      transmitted RPM data. Variables associated with RPM enrollment and activation
      were identified with the use of multivariable logistic regression. Among 39 158
      patients with newly implanted RPM-capable devices, 62% (n=24 113) were RPM
      enrolled. Of those enrolled, 76% (n=18 289, or 47% of the entire cohort)
      activated their device. RPM enrollment was highly variable among institutions.
      The hospital-specific median odds ratio for RPM enrollment was 3.43, signifying
      that physician or institutional factors are associated with RPM enrollment. In
      contrast, the hospital-specific median odds ratio for RPM activation was 1.69.
      Age, race, health insurance, geographic location, and health-related factors were
      similarly associated with both RPM enrollment and activation. CONCLUSIONS: RPM
      technology is used in less than half of eligible patients. Lack of enrollment
      into RPM systems is the major cause of underutilization, and this primarily
      relates to the local practice environment.

PMID- 24043300
TI  - Novel small leucine-rich repeat protein podocan is a negative regulator of
      migration and proliferation of smooth muscle cells, modulates neointima
      formation, and is expressed in human atheroma.
AB  - BACKGROUND: Smooth muscle cell (SMC) migration and proliferation critically
      influence the clinical course of vascular disease. We tested the effect of the
      novel small leucine-rich repeat protein podocan on SMC migration and
      proliferation using a podocan-deficient mouse in combination with a model of
      arterial injury and aortic explant SMC culture. In addition, we examined the
      effect of overexpression of the human form of podocan on human SMCs and tested
      for podocan expression in human atherosclerosis. In all these conditions, we
      concomitantly evaluated the Wnt-TCF (T-cell factor) pathway. METHODS AND RESULTS:
      Podocan was strongly and selectively expressed in arteries of wild-type mice
      after injury. Podocan-deficient mice showed increased arterial lesion formation
      compared with wild-type littermates in response to injury (P<0.05). Also, SMC
      proliferation was increased in arteries of podocan-deficient mice compared with
      wild-type (P<0.05). In vitro, migration and proliferation were increased in
      podocan-deficient SMCs and were normalized by transfection with the wild-type
      podocan gene (P<0.05). In addition, upregulation of the Wnt-TCF pathway was found
      in SMCs of podocan-deficient mice both in vitro and in vivo. On the other hand,
      podocan overexpression in human SMCs significantly reduced SMC migration and
      proliferation, inhibiting the Wnt-TCF pathway. Podocan and a Wnt-TCF pathway
      marker were differently expressed in human coronary restenotic versus primary
      lesions. CONCLUSIONS: Podocan appears to be a potent negative regulator of the
      migration and proliferation of both murine and human SMCs. The lack of podocan
      results in excessive arterial repair and prolonged SMC proliferation, which
      likely is mediated by the Wnt-TCF pathway.

PMID- 24043303
TI  - The ubiquitin ligase CHIP prevents SirT6 degradation through noncanonical
      ubiquitination.
AB  - The ubiquitin ligase CHIP (carboxyl terminus of Hsp70-interacting protein)
      regulates protein quality control, and CHIP deletion accelerates aging and
      reduces the life span in mice. Here, we reveal a mechanism for CHIP's influence
      on longevity by demonstrating that CHIP stabilizes the sirtuin family member
      SirT6, a lysine deacetylase/ADP ribosylase involved in DNA repair, metabolism,
      and longevity. In CHIP-deficient cells, SirT6 protein half-life is substantially
      reduced due to increased proteasome-mediated degradation, but CHIP overexpression
      in these cells increases SirT6 protein expression without affecting SirT6
      transcription. CHIP noncanonically ubiquitinates SirT6 at K170, which stabilizes
      SirT6 and prevents SirT6 canonical ubiquitination by other ubiquitin ligases. In
      CHIP-depleted cells, SirT6 K170 mutation increases SirT6 half-life and prevents
      proteasome-mediated degradation. The global decrease in SirT6 expression in the
      absence of CHIP is associated with decreased SirT6 promoter occupancy, which
      increases histone acetylation and promotes downstream gene transcription in CHIP
      depleted cells. Cells lacking CHIP are hypersensitive to DNA-damaging agents, but
      DNA repair and cell viability are rescued by enforced expression of SirT6. The
      discovery of this CHIP-SirT6 interaction represents a novel protein-stabilizing
      mechanism and defines an intersection between protein quality control and
      epigenetic regulation to influence pathways that regulate the biology of aging. 

PMID- 24043304
TI  - Poly(ADP-ribose) polymerase 1 promotes oxidative-stress-induced liver cell death
      via suppressing farnesoid X receptor alpha.
AB  - Farnesoid X receptor alpha (FXR) is highly expressed in the liver and regulates
      the expression of various genes involved in liver repair. In this study, we
      demonstrated that activated poly(ADP-ribose) polymerase 1 (PARP1) promoted
      hepatic cell death by inhibiting the expression of FXR-dependent hepatoprotective
      genes. PARP1 could bind to and poly(ADP-ribosyl)ate FXR. Poly(ADP-ribosyl)ation
      dissociated FXR from the FXR response element (FXRE), present in the promoters of
      target genes, and suppressed FXR-mediated gene transcription. Moreover, treatment
      with a FXR agonist attenuated poly(ADP-ribosyl)ation of FXR and promoted FXR
      dependent gene expression. We further established the CCl4-induced acute liver
      injury model in wild-type and FXR-knockout mice and identified an essential role
      of FXR poly(ADP-ribosyl)ation in CCl4-induced liver injury. Thus, our results
      identified poly(ADP-ribosyl)ation of FXR by PARP1 as a key step in oxidative
      stress-induced hepatic cell death. The molecular association between PARP1 and
      FXR provides new insight into the mechanism, suggesting that inhibition of PARP1
      could prevent liver injury. 

PMID- 24043305
TI  - Genomic and proteomic analyses of Prdm5 reveal interactions with insulator
      binding proteins in embryonic stem cells.
AB  - PRDM proteins belong to the SET domain protein family, which is involved in the
      regulation of gene expression. Although few PRDM members possess histone
      methyltransferase activity, the molecular mechanisms by which the other members
      exert transcriptional regulation remain to be delineated. In this study, we find
      that Prdm5 is highly expressed in mouse embryonic stem (mES) cells and exploit
      this cellular system to characterize molecular functions of Prdm5. By combining
      proteomics and next-generation sequencing technologies, we identify Prdm5
      interaction partners and genomic occupancy. We demonstrate that although Prdm5 is
      dispensable for mES cell maintenance, it directly targets genomic regions
      involved in early embryonic development and affects the expression of a subset of
      developmental regulators during cell differentiation. Importantly, Prdm5
      interacts with Ctcf, cohesin, and TFIIIC and cooccupies genomic loci. In summary,
      our data indicate how Prdm5 modulates transcription by interacting with factors
      involved in genome organization in mouse embryonic stem cells. 

PMID- 24043306
TI  - Phosphorylation of Rac1 T108 by extracellular signal-regulated kinase in response
      to epidermal growth factor: a novel mechanism to regulate Rac1 function.
AB  - Accumulating evidence has implicated Rho GTPases, including Rac1, in many aspects
      of cancer development. Recent findings suggest that phosphorylation might further
      contribute to the tight regulation of Rho GTPases. Interestingly, sequence
      analysis of Rac1 shows that Rac1 T108 within the (106)PNTP(109) motif is likely
      an extracellular signal-regulated kinase (ERK) phosphorylation site and that Rac1
      also has an ERK docking site, (183)KKRKRKCLLL(192) (D site), at the C terminus.
      Indeed, we show here that both transfected and endogenous Rac1 interacts with ERK
      and that this interaction is mediated by its D site. Green fluorescent protein
      (GFP)-Rac1 is threonine (T) phosphorylated in response to epidermal growth factor
      (EGF), and EGF-induced Rac1 threonine phosphorylation is dependent on the
      activation of ERK. Moreover, mutant Rac1 with the mutation of T108 to alanine (A)
      is not threonine phosphorylated in response to EGF. In vitro ERK kinase assay
      further shows that pure active ERK phosphorylates purified Rac1 but not mutant
      Rac1 T108A. We also show that Rac1 T108 phosphorylation decreases Rac1 activity,
      partially due to inhibiting its interaction with phospholipase C-gamma1 (PLC
      gamma1). T108 phosphorylation targets Rac1 to the nucleus, which isolates Rac1
      from other guanine nucleotide exchange factors (GEFs) and hinders Rac1's role in
      cell migration. We conclude that Rac1 T108 is phosphorylated by ERK in response
      to EGF, which plays an important role in regulating Rac1. 

PMID- 24043307
TI  - MEF2 is a converging hub for histone deacetylase 4 and phosphatidylinositol 3
      kinase/Akt-induced transformation.
AB  - The MEF2-class IIa histone deacetylase (HDAC) axis operates in several
      differentiation pathways and in numerous adaptive responses. We show here that
      nuclear active HDAC4 and HDAC7 display transforming capability. HDAC4 oncogenic
      potential depends on the repression of a limited set of genes, most of which are
      MEF2 targets. Genes verified as targets of the MEF2-HDAC axis are also under the
      influence of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway that affects
      MEF2 protein stability. A signature of MEF2 target genes identified by this study
      is recurrently repressed in soft tissue sarcomas. Correlation studies depicted
      two distinct groups of soft tissue sarcomas: one in which MEF2 repression
      correlates with PTEN downregulation and a second group in which MEF2 repression
      correlates with HDAC4 levels. Finally, simultaneous pharmacological inhibition of
      the PI3K/Akt pathway and of MEF2-HDAC interaction shows additive effects on the
      transcription of MEF2 target genes and on sarcoma cells proliferation. Overall,
      our work pinpoints an important role of the MEF2-HDAC class IIa axis in
      tumorigenesis. 

PMID- 24043308
TI  - A novel role for keratin 17 in coordinating oncogenic transformation and cellular
      adhesion in Ewing sarcoma.
AB  - Oncogenic transformation in Ewing sarcoma is caused by EWS/FLI, an aberrant
      transcription factor fusion oncogene. Glioma-associated oncogene homolog 1 (GLI1)
      is a critical target gene activated by EWS/FLI, but the mechanism by which GLI1
      contributes to the transformed phenotype of Ewing sarcoma was unknown. In this
      work, we identify keratin 17 (KRT17) as a direct downstream target gene
      upregulated by GLI1. We demonstrate that KRT17 regulates cellular adhesion by
      activating AKT/PKB (protein kinase B) signaling. In addition, KRT17 is necessary
      for oncogenic transformation in Ewing sarcoma and accounts for much of the GLI1
      mediated transformation function but via a mechanism independent of AKT
      signaling. Taken together, our data reveal previously unknown molecular functions
      for a cytoplasmic intermediate filament protein, KRT17, in coordinating EWS/FLI-
      and GLI1-mediated oncogenic transformation and cellular adhesion in Ewing
      sarcoma. 

PMID- 24043309
TI  - AMP-activated protein kinase alpha1 but not alpha2 catalytic subunit potentiates
      myogenin expression and myogenesis.
AB  - The link between AMP-activated protein kinase (AMPK) and myogenesis remains
      poorly defined. AMPK has two catalytic alpha subunits, alpha1 and alpha2. We
      postulated that AMPK promotes myogenesis in an isoform-specific manner. Primary
      myoblasts were prepared from AMPK knockout (KO) mice and AMPK conditional KO
      mice, and knockout of the alpha1 but not the alpha2 subunit resulted in
      downregulation of myogenin and reduced myogenesis. Myogenin expression and
      myogenesis were nearly abolished in the absence of both AMPKalpha1 and
      AMPKalpha2, while enhanced AMPK activity promoted myogenesis and myotube
      formation. The AMPKalpha1-specific effect on myogenesis was likely due to the
      dominant expression of alpha1 in myoblasts. These results were confirmed in C2C12
      cells. To further evaluate the necessity of the AMPKalpha1 subunit for myogenesis
      in vivo, we prepared both DsRed AMPKalpha1 knockout myoblasts and enhanced green
      fluorescent protein (EGFP) wild-type myoblasts, which were cotransplanted into
      tibialis anterior muscle. A number of green fluorescent muscle fibers were
      observed, showing the fusion of engrafted wild-type myoblasts with muscle fibers;
      on the other hand, very few or no red muscle fibers were observed, indicating the
      absence of myogenic capacity of AMPKalpha1 knockout myoblasts. In summary, these
      results indicate that AMPK activity promotes myogenesis through a mechanism
      mediated by AMPKalpha1. 

PMID- 24043310
TI  - SIRT4 represses peroxisome proliferator-activated receptor alpha activity to
      suppress hepatic fat oxidation.
AB  - Sirtuins are a family of protein deacetylases, deacylases, and ADP
      ribosyltransferases that regulate life span, control the onset of numerous age
      associated diseases, and mediate metabolic homeostasis. We have uncovered a novel
      role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid
      metabolism during changes in nutrient availability. We show that SIRT4 levels
      decrease in the liver during fasting and that SIRT4 null mice display increased
      expression of hepatic peroxisome proliferator-activated receptor alpha
      (PPARalpha) target genes associated with fatty acid catabolism. Accordingly,
      primary hepatocytes from SIRT4 knockout (KO) mice exhibit higher rates of fatty
      acid oxidation than wild-type hepatocytes, and SIRT4 overexpression decreases
      fatty acid oxidation rates. The enhanced fatty acid oxidation observed in SIRT4
      KO hepatocytes requires functional SIRT1, demonstrating a clear cross talk
      between mitochondrial and nuclear sirtuins. Thus, SIRT4 is a new component of
      mitochondrial signaling in the liver and functions as an important regulator of
      lipid metabolism. 

PMID- 24043311
TI  - Extracellular signal-regulated kinase regulates RhoA activation and tumor cell
      plasticity by inhibiting guanine exchange factor H1 activity.
AB  - In certain Ras mutant cell lines, the inhibition of extracellular signal
      regulated kinase (ERK) signaling increases RhoA activity and inhibits cell
      motility, which was attributed to a decrease in Fra-1 levels. Here we report a
      Fra-1-independent augmentation of RhoA signaling during short-term inhibition of
      ERK signaling. Using mass spectrometry-based proteomics, we identified guanine
      exchange factor H1 (GEF-H1) as mediating this effect. ERK binds to the Rho
      exchange factor GEF-H1 and phosphorylates it on S959, causing inhibition of GEF
      H1 activity and a consequent decrease in RhoA activity. Knockdown experiments and
      expression of a nonphosphorylatable S959A GEF-H1 mutant showed that this site is
      crucial in regulating cell motility and invasiveness. Thus, we identified GEF-H1
      as a critical ERK effector that regulates motility, cell morphology, and
      invasiveness. 

PMID- 24043312
TI  - Functional redundancy of Sos1 and Sos2 for lymphopoiesis and organismal
      homeostasis and survival.
AB  - Sos1 and Sos2 are ubiquitously expressed, universal Ras guanine nucleotide
      exchange factors (Ras-GEFs) acting in multiple signal transduction pathways
      activated by upstream cellular kinases. The embryonic lethality of Sos1 null
      mutants has hampered ascertaining the specific in vivo contributions of Sos1 and
      Sos2 to processes controlling adult organism survival or development of
      hematopoietic and nonhematopoietic organs, tissues, and cell lineages. Here, we
      generated a tamoxifen-inducible Sos1-null mouse strain allowing analysis of the
      combined disruption of Sos1 and Sos2 (Sos1/2) during adulthood. Sos1/2 double
      knockout (DKO) animals died precipitously, whereas individual Sos1 and Sos2
      knockout (KO) mice were perfectly viable. A reduced percentage of total bone
      marrow precursors occurred in single-KO animals, but a dramatic depletion of B
      cell progenitors was specifically detected in Sos1/2 DKO mice. We also confirmed
      a dominant role of Sos1 over Sos2 in early thymocyte maturation, with almost
      complete thymus disappearance and dramatically higher reduction of absolute
      thymocyte counts in Sos1/2 DKO animals. Absolute counts of mature B and T cells
      in spleen and peripheral blood were unchanged in single-KO mutants, while
      significantly reduced in Sos1/2 DKO mice. Our data demonstrate functional
      redundancy between Sos1 and Sos2 for homeostasis and survival of the full
      organism and for development and maturation of T and B lymphocytes. 

PMID- 24043313
TI  - Novel role of calmodulin in regulating protein transport to mitochondria in a
      unicellular eukaryote.
AB  - Lower eukaryotes like the kinetoplastid parasites are good models to study
      evolution of cellular pathways during steps to eukaryogenesis. In this study, a
      kinetoplastid parasite, Leishmania donovani, was used to understand the process
      of mitochondrial translocation of a nucleus-encoded mitochondrial protein, the
      mitochondrial tryparedoxin peroxidase (mTXNPx). We report the presence of an N
      terminal cleavable mitochondrial targeting signal (MTS) validated through
      deletion and grafting experiments. We also establish a novel finding of
      calmodulin (CaM) binding to the MTS of mTXNPx through specific residues. Mutation
      of CaM binding residues, keeping intact the residues involved in mitochondrial
      targeting and biochemical inhibition of CaM activity both in vitro and in vivo,
      prevented mitochondrial translocation. Through reconstituted import assays, we
      demonstrate obstruction of mitochondrial translocation either in the absence of
      CaM or Ca(2+) or in the presence of CaM inhibitors. We also demonstrate the
      prevention of temperature-driven mTXNPx aggregation in the presence of CaM. These
      findings establish the idea that CaM is required for the transport of the protein
      to mitochondria through maintenance of translocation competence posttranslation. 

PMID- 24043314
TI  - Synthesis of supported Ni@(RhNi-alloy) nanocomposites as an efficient catalyst
      towards hydrogen generation from N2H4BH3.
AB  - Supported Ni@(RhNi-alloy) nanoparticles with a core-shell structure were
      prepared, which serve as an excellent catalyst towards hydrogen generation from
      N2H4BH3. 

PMID- 24043315
TI  - Anatomical study on the sinuatrial nodal branch in the human coronary artery.
AB  - The sinuatrial nodal branch (SANB) of the coronary artery is anatomically
      important as it irrigates the sinuatrial node. Past studies on the origin and
      route of the SANB in the human heart have produced discrepant findings.
      Therefore, in this study, we macroscopically investigated the origin, route, and
      distribution of the SANB in 293 human hearts. In addition, we examined the
      relationship between coronary artery dominance and the origin of the SANB. The
      SANB was found to have one branch in 267 specimens (91.2%), two branches in 25
      specimens (8.5%), and three branches in one (0.3%) specimen. The SANB originated
      from the right coronary artery in 184 branches (57.5%) and from the left coronary
      artery (circumflex artery) in 136 branches (42.5%). Nine SANB routes were
      classified, all of which were distributed in the interatrial septum except for
      one heart with a type R3 SANB course, which was found to extend through the
      muscle layer of the interatrial septum into the septum. The composition of these
      courses could relate to the generation of the proepicardium in the amniote.

PMID- 24043316
TI  - Obstructive Thebesian valve: anatomical study and implications for invasive
      cardiologic procedures.
AB  - Thebesian valve is the embryological remnant of the right sinoatrial valve,
      guarding the coronary sinus (CS) ostium. Advanced invasive and interventional
      cardiac diagnostic and management tools involve cannulation of the CS ostium. The
      presence of obstructive Thebesian valves has been reported to lead to
      unsuccessful cannulation of the CS. We studied the morphology of the Thebesian
      valve and CS ostium to assess the possible impact of these structures on invasive
      cardiological procedures. One hundred fifty randomly selected human cadaveric
      heart specimens fixed in 10% formalin were dissected in the customary routine
      manner. The Thebesian valves were classified according to their shape as
      semilunar/fenestrated/biconcave band like and according to their composition as
      membranous/fibromuscular/fibrous/muscular, and the extent to which the valve
      covered the CS ostium was also noted. An obstructive Thebesian valve that could
      interfere with the cannulation of the CS was defined as non-fenestrated
      (semilunar/biconcave band like) and non-membranous
      (fibromuscular/fibrous/muscular) valves covering >75% of the CS ostium. Thebesian
      valves were present in 118 (79%) heart specimens, of which 27 (18%) met the
      criteria of being obstructive. Semilunar was the most common type of Thebesian
      valve in terms of shape and was observed in 65 (65/118; 55%) hearts. This type
      was associated with the least mean craniocaudal (7.9+/-0.6 mm) and mean
      transverse (6.25+/-0.6 mm) diameters of the CS ostium. The mean craniocaudal
      diameter of the CS ostium (9.4+/-2.1 mm) was significantly larger (p=0.004) than
      the mean transverse diameter (7.15+/-1.5 mm) in specimens with Thebesian valves,
      and the cranial margin of the CS ostium was free from any attachment of the
      Thebesian valve in all the types observed (in terms of shape). Hence, attempts to
      direct the tip of the catheter toward the cranial margin of the CS ostium under
      direct vision may lead to successful cannulation of the same when conventional
      techniques have been unsuccessful because of the presence of an obstructive
      Thebesian valve.

PMID- 24043317
TI  - Medical decision support using machine learning for early detection of late-onset
      neonatal sepsis.
AB  - OBJECTIVE: The objective was to develop non-invasive predictive models for late
      onset neonatal sepsis from off-the-shelf medical data and electronic medical
      records (EMR). DESIGN: The data used in this study are from 299 infants admitted
      to the neonatal intensive care unit in the Monroe Carell Jr. Children's Hospital
      at Vanderbilt and evaluated for late-onset sepsis. Gold standard diagnostic
      labels (sepsis negative, culture positive sepsis, culture negative/clinical
      sepsis) were assigned based on all the laboratory, clinical and microbiology data
      available in EMR. Only data that were available up to 12 h after phlebotomy for
      blood culture testing were used to build predictive models using machine learning
      (ML) algorithms. MEASUREMENT: We compared sensitivity, specificity, positive
      predictive value and negative predictive value of sepsis treatment of physicians
      with the predictions of models generated by ML algorithms. RESULTS: The treatment
      sensitivity of all the nine ML algorithms and specificity of eight out of the
      nine ML algorithms tested exceeded that of the physician when culture-negative
      sepsis was included. When culture-negative sepsis was excluded both sensitivity
      and specificity exceeded that of the physician for all the ML algorithms. The top
      three predictive variables were the hematocrit or packed cell volume,
      chorioamnionitis and respiratory rate. CONCLUSIONS: Predictive models developed
      from off-the-shelf and EMR data using ML algorithms exceeded the treatment
      sensitivity and treatment specificity of clinicians. A prospective study is
      warranted to assess the clinical utility of the ML algorithms in improving the
      accuracy of antibiotic use in the management of neonatal sepsis.

PMID- 24043318
TI  - Applying operations research to optimize a novel population management system for
      cancer screening.
AB  - OBJECTIVE: To optimize a new visit-independent, population-based cancer screening
      system (TopCare) by using operations research techniques to simulate changes in
      patient outreach staffing levels (delegates, navigators), modifications to user
      workflow within the information technology (IT) system, and changes in cancer
      screening recommendations. MATERIALS AND METHODS: TopCare was modeled as a
      multiserver, multiphase queueing system. Simulation experiments implemented the
      queueing network model following a next-event time-advance mechanism, in which
      systematic adjustments were made to staffing levels, IT workflow settings, and
      cancer screening frequency in order to assess their impact on overdue screenings
      per patient. RESULTS: TopCare reduced the average number of overdue screenings
      per patient from 1.17 at inception to 0.86 during simulation to 0.23 at steady
      state. Increases in the workforce improved the effectiveness of TopCare. In
      particular, increasing the delegate or navigator staff level by one person
      improved screening completion rates by 1.3% or 12.2%, respectively. In contrast,
      changes in the amount of time a patient entry stays on delegate and navigator
      lists had little impact on overdue screenings. Finally, lengthening the screening
      interval increased efficiency within TopCare by decreasing overdue screenings at
      the patient level, resulting in a smaller number of overdue patients needing
      delegates for screening and a higher fraction of screenings completed by
      delegates. CONCLUSIONS: Simulating the impact of changes in staffing, system
      parameters, and clinical inputs on the effectiveness and efficiency of care can
      inform the allocation of limited resources in population management.

PMID- 24043319
TI  - Graphene@poly(m-phenylenediamine) hydrogel fabricated by a facile post-synthesis
      assembly strategy.
AB  - The mixing of graphene oxide and protonated poly(m-phenylenediamine) (PmPD)
      nanoparticles generates floccus that can be readily transformed into
      graphene@PmPD hybrid hydrogel through redox reaction. This macroscopic material
      can be directly applied as a monolith column adsorbent for water purification. 

PMID- 24043320
TI  - Pathogenetic role for early focal macrophage infiltration in a pig model of
      arteriovenous fistula (AVF) stenosis.
AB  - PURPOSE: Arteriovenous fistula non-maturation because of a peri-anastomotic
      venous stenosis is currently a huge clinical problem for which there are no
      effective therapies. METHODS: In an attempt to further define the cellular
      pathways involved in this process we have assessed the pattern and intensity of
      macrophage infiltration at different time points in a pig model of AVF stenosis.
      RESULTS: Our results demonstrate an early and eccentric pattern of macrophage
      infiltration at 2d with a rapid disappearance of this infiltrate by 7d.
      CONCLUSION: We suggest that this early and eccentric macrophage infiltration
      could play an important role in the pathogenesis of AVF non-maturation.

PMID- 24043321
TI  - Safety of percutaneous tunneled hemodialysis catheter procedures in patients
      receiving concurrent clopidogrel therapy.
AB  - PURPOSE: Patients on clopidogrel are at increased risk of bleeding. This study
      was commenced to assess the incidence of bleeding in dialysis patients who
      underwent tunneled hemodialysis catheter procedures while on clopidogrel therapy.
      METHODS: This is a single center retrospective study of 25 (10 men, 15 women;
      median age 70) dialysis patients in whom clopidogrel could not be discontinued
      and underwent tunneled hemodialysis catheter insertion, removal or exchange
      between the period March 2010 to November 2011. The medical records of patients
      were reviewed and complications were classified according to the Society of
      Interventional Radiology system. Fifty-three procedures (22 insertions, 11
      exchanges and 20 removals) were performed in these patients. The pre-procedural
      median platelet count, International Normalized Ratio and partial thromboplastin
      time were 195*103/dL (range 50-666), 1.1 (range 0.9-3.3) and 26.3 seconds (range
      22.5-69.8) respectively. RESULTS AND CONCLUSIONS: Forty-six procedures were
      performed in patients on clopidogrel and aspirin treatment. Five procedures were
      performed in patients while on clopidogrel in combination with aspirin and
      warfarin, and two procedures were performed with patients on clopidogrel alone.
      There were no documented bleeding complications from tunneled hemodialysis
      catheter procedures performed in patients on concurrent clopidogrel therapy in
      our study. Further prospective assessment with a larger cohort is necessary in
      order to validate these findings.

PMID- 24043322
TI  - Venous International Assessment, VIA scale, validated classification procedure
      for the peripheral venous system.
AB  - PURPOSE: VIA scale is a dynamic performance status tool of the peripheral venous
      system that is divided into five different grades, composed of three parameters:
      number of observable puncture points; optimal catheter size for cannulation and
      ease of performing venipuncture and risk of extravasation. METHODS: Prospective
      single-center, observational, open, non-randomized study divided into two phases.
      In the first longitudinal phase, we studied the clinical characteristics and the
      changes in their peripheral venous systems during intravenous chemotherapy for 16
      patients (n=16) for an average period of 24 months. In the second transverse
      phase, we measured the vein's diameter at the selected puncture points with a
      high-resolution ultrasound and paired this figure with VIA scale. We selected a
      group of oncology patients (n=52) and a control group (n=56). RESULTS: In the
      first phase, the level of agreement between the three reviewers was excellent.
      The second step was to assess the relationship between the measurements obtained
      with ultrasound and the VIA scale. The vein diameter measurements show a decrease
      directly related to the assessment of observers in the VIA scale. CONCLUSIONS:
      The VIA scale is a simple, easy and practical method for classification of the
      peripheral venous system in terms of vascular access. The practical application
      of our VIA scale significantly increases the quality of life of patients by
      increasing the chances of successful venipuncture and cannulation and thus
      reducing the risk of extravasation and material costs, allowing both an
      economical and a safe venous assessment tool.

PMID- 24043323
TI  - Evaluation for hypoperfusion distal to arteriovenous vascular access using skin
      perfusion pressure in fingers.
AB  - PURPOSE: The usefulness of skin perfusion pressure (SPP) measurement in the
      assessment of critical ischemia of the lower limb has previously been
      established. This study investigated whether finger SPP measurement is useful to
      evaluate hypoperfusion distal to arteriovenous vascular access in dialysis
      patients. METHODS: Seventeen asymptomatic hemodialysis patients with upper
      extremity arteriovenous access and 17 non-dialysis control patients were
      prospectively examined. SPP in the thumb, the middle finger and the little finger
      of both hands was measured. The bilateral difference of the mean SPP of the three
      fingers was evaluated. RESULTS: The mean difference of SPP between the
      contralateral and the arteriovenous access sides among hemodialysis patients
      (33+/-2 5 mmHg) was significantly larger than the mean difference of SPP between
      the left and the right hands among control patients (1.0+/-6.0 mmHg, p<0.01).
      CONCLUSIONS: This report shows the potential usefulness of SPP measurement to
      evaluate hypoperfusion distal to arteriovenous vascular access.

PMID- 24043324
TI  - Arteriovenous fistula formations: key to vascular surgical training.
AB  - PURPOSE: To highlight missed training opportunities in daycase surgery for
      trainees to acquire competency in vascular anastomosis by performing
      arteriovenous fistula (AVF) formations. METHODS: Operative Room Management
      Information System records were reviewed for AVF procedures in daycase and
      general theatres at a UK Foundation Trust between 2007 and 2012. Data collected
      included procedure, procedure time (PT), patient length of stay (LOS),
      readmissions within 30 days of procedure and lead and assistant surgeons
      involved. RESULTS: Of 199 daycase AVF procedures reviewed, 59.3% (n=118) were
      brachiocephalic formations and 34.2% (n=68) radiocephalic formations. Trainees
      attended 41.2% of daycase AVF procedures and were lead surgeon in 7.3% of these.
      Mean PT was 64 minutes for consultants compared with 56 minutes for trainees,
      with no significant difference (p=0.297). Median patient LOS was less than 24
      hours for both groups. Six daycase AVF procedures resulted in patient readmission
      within 30 days; five of these were operated on by consultants and one by a staff
      grade. During the same period, 258 AVF procedures were performed in general
      theatres. Trainees attended 64.3% of AVF formations performed in general theatres
      and were lead surgeon in 5.8% of these. CONCLUSIONS: Trainees attended and led
      few daycase AVF formations despite no significant difference in PT, patient LOS
      or readmission rate between consultant-led and trainee-led cases. Trainees
      attended more AVF formations performed in general theatres than daycase. However,
      trainees led a greater proportion of daycase AVF formations, possibly due to a
      less complex case mix that is more suitable for training.

PMID- 24043325
TI  - Ipsilateral jugular access to treat an otherwise inaccessible puncture-related
      arteriovenous fistula pseudoaneurysm: a technical note.
AB  - BACKGROUND: The standard approach for the endovascular treatment of a
      dysfunctional or occluded hemodialysis access in the upper limbs includes a
      direct intervention through the access itself or alternatively, when not
      feasible, through the brachial or radial artery access. Nonetheless, there are
      certain circumstances in which these approaches are not easily achieved. METHODS:
      An 89-year-old male with end-stage renal disease developed a pseudoaneurysm after
      an hemorrhagic complication of a recently transposed native basilic arteriovenous
      fistula secondary to a needle puncture. Dehiscence of the injured access with
      spontaneous arterial bleeding evolved as a consequence of the upper limb
      swelling, rendering therapeutic intervention of the access through a conventional
      route impossible. A fistulogram through puncture of the common femoral artery was
      performed to obtain an accurate diagnosis. However, this approach was
      insufficient to advance the covered stent with the intention of excluding the
      pseudoaneurysm, as the stent delivery system could not reach the desired site.
      Given that the covered stent insertion required a 9 Fr introducer, the radial
      artery approach was ruled out. Therefore, we chose a venous access via the
      ipsilateral internal jugular vein, which was punctured under ultrasound guidance.
      RESULTS: This strategy was useful to advance the stent and exclude the
      pseudoaneurysm successfully. CONCLUSIONS: This technique should be considered for
      those individuals in whom conventional routes of approach for repairing dialysis
      accesses are not feasible or are extremely risky.

PMID- 24043326
TI  - Implanted central venous access ports for therapeutic phlebotomy in patients with
      HFE hemochromatosis and other non-thalassemia iron overload disorders.

PMID- 24043327
TI  - Brachial artery aneurysms following brachio-cephalic AV fistula ligation.
AB  - PURPOSE: Peripheral artery aneurysms proximal to a long-standing arteriovenous
      (AV) fistula can be a serious complication. It is important to be aware of this
      and manage it appropriately. METHODS: Vascular access nurses input all data
      regarding patients undergoing dialysis access procedures into a securely held
      database prospectively. This was retrospectively reviewed to identify cases of
      brachial artery aneurysms over the last 3 years. RESULTS: In Morriston Hospital,
      around 200 forearm and arm AV fistulas are performed annually for vascular access
      in renal dialysis patients. Of these, approximately 15 (7.5%) are ligated. Three
      patients who had developed brachial artery aneurysms following AV fistula
      ligation were identified. All 3 patients had developed brachial artery aneurysms
      following ligation of a long-standing brachio-cephalic AV fistula. Two patients
      presented with pain and a pulsatile mass in the arm, and one presented with pins
      and needles and discoloration of fingertips. Two were managed with resection of
      the aneurysm and reconstruction with a reversed long saphenous vein interposition
      graft, the third simply required ligation of a feeding arterial branch.
      CONCLUSIONS: True aneurysm formation proximal to an AV fistula that has been
      ligated is a rare complication. There are several reasons for why these aneurysms
      develop in such patients, the most plausible one being the increase in blood flow
      and resistance following ligation of the AV fistula. Of note, all the patients in
      this study were on immunosuppressive therapy following successful renal
      transplantation. Vigilance by the vascular access team and nephrologists is
      paramount to identify those patients who may warrant further evaluation and
      investigation by the vascular surgeon.

PMID- 24043328
TI  - Salvage of radiocephalic arteriovenous fistula in hemodialysis patient causing
      steal syndrome with endovascular coil embolization.

PMID- 24043329
TI  - Peritoneal dialysis access: open versus laparoscopic surgical techniques.
AB  - AIM: To outline pros and cons with the open and laparoscopic techniques when
      placing peritoneal dialysis (PD) catheters. BACKGROUND: Controversy exists
      regarding which technique, the open and laparoscopic, if any, is superior to the
      other. In addition, there is the question of which approach is best in rescuing
      malfunctioning PD catheters. RESULTS: Rather than promoting one doctrine fits
      all, philosophically, doing the right thing for the patient by specific criteria
      is ethically the better model. These specific selection criteria include patient
      characteristics, the team's skills and knowledge and institutional resources and
      commitment. Also, the sophistication of a PD unit for training and monitoring of
      patients is crucial for successful outcomes. Open paramedian and two laparoscopic
      approaches are described in detail, outlining advantages and disadvantages of
      each, with suggestions when one method is preferred. CONCLUSIONS: In general, the
      laparoscopic technique is associated with longer operative times, higher costs
      and the need to utilize general anesthesia. It is, however, the preferred method
      when rescuing malfunctioning catheters and may increase the PD patient population
      in patients with previous abdominal surgeries. The dialysis access surgeon should
      be familiar with both open and laparoscopic techniques and appropriately choose
      the ideal method based upon the individual patient and institutional resources.

PMID- 24043330
TI  - Arteriovenous fistula creation using the OptiflowTM vascular anastomotic
      connector: the OPEN (Optiflow PatEncy and MaturatioN) study.
AB  - PURPOSE: Arteriovenous fistulas (AVFs) are the preferred form of vascular access
      for hemodialysis. However, non-maturation and patency are major clinical
      problems. The OptiflowTM device is an implantable anastomotic connector used to
      standardize the creation of an AVF. Studies have suggested that the geometry of
      the anastomosis and experience of the surgeon impact patency and maturation
      rates. The Optiflow serves as a surgical template whereby the geometry and flow
      path of the anastomosis are predetermined. This prospective study was intended to
      evaluate maturation, patency and safety of the Optiflow. METHODS: Forty-one upper
      arm AVFs were created in 41 end-stage renal disease patients using the Optiflow
      device at two investigational sites. Patients were followed for 90 days with
      serial Doppler ultrasounds performed at approximately 14, 42 and 90 days to
      determine AVF maturation. The primary performance endpoint was unassisted
      maturation, defined as an outflow vein that was equal to or greater than 5 mm in
      diameter, and with flow equal to or greater than 500 mL/min without the need for
      any intervention intended to promote or maintain maturation. The primary safety
      endpoint was the rate of device-related serious adverse events. RESULTS:
      Unassisted maturation rates were 76%, 72% and 68% and unassisted patency rates
      were 93%, 88% and 78%, at 14, 42 and 90 days, respectively. There were no device
      related serious adverse events. CONCLUSIONS: The results suggest that the
      Optiflow is safe for its intended use and could play an important role in
      enhancing AVF maturation while standardizing the anastomotic technique.

PMID- 24043331
TI  - Optimizing reperfusion in patients with STEMI: a critical evaluation of
      pharmacologic and non-pharmacologic strategies.
AB  - Among patients with ST-elevation myocardial infarction (STEMI), rapidly re
      establishing normal coronary blood flow is of paramount importance. More than 25
      % of hospitals in the USA do not have access to timely primary percutaneous
      coronary intervention, highlighting the need for clinicians to understand both
      pharmacologic and non-pharmacologic strategies for STEMI. This manuscript reviews
      the current state of the art in STEMI care, describing both pharmacologic and non
      pharmacologic strategies for reperfusion. 

PMID- 24043332
TI  - [First guidelines of the Brazilian Society of Cardiology on processes and skills
      for education in cardiology in Brazil].

PMID- 24043333
TI  - A knockdown mutation of YELLOW-GREEN LEAF2 blocks chlorophyll biosynthesis in
      rice.
AB  - KEY MESSAGE: An insert mutation of YELLOW-GREEN LEAF2 , encoding Heme Oxygenase 1
      , results in significant reduction of its transcript levels, and therefore
      impairs chlorophyll biosynthesis in rice. Heme oxygenase (HO) in higher plants
      catalyzes the degradation of heme to synthesize phytochrome precursor and its
      roles conferring the photoperiodic control of flowering in rice have been
      revealed. However, its involvement in regulating rice chlorophyll (Chl) synthesis
      is not fully explored. In this study, we isolated a rice mutant named yellow
      green leaf 2 (ygl2) from a (60)Co-irradiated population. Normal grown ygl2
      seedlings showed yellow-green leaves with reduced contents of Chl and
      tetrapyrrole intermediates whereas an increase of Chl a/b ratio. Ultrastructural
      analyses demonstrated grana were poorly stacked in ygl2 mutant, resulting in
      underdevelopment of chloroplasts. The ygl2 locus was mapped to chromosome 6 and
      isolated via map-based cloning. Sequence analysis indicated that it encodes the
      rice HO1 and its identity was verified by transgenic complementation test and RNA
      interference. A 7-Kb insertion was found in the first exon of YGL2/HO1, resulting
      in significant reduction of YGL2 expressions in the ygl2 mutant. YGL2 was
      constitutively expressed in a variety of rice tissues with the highest levels in
      leaves and regulated by temperature. In addition, we found expression levels of
      some genes associated with Chl biosynthesis and photosynthesis were concurrently
      altered in ygl2 mutant. These results provide direct evidence that YGL2 has a
      vital function in rice Chl biosynthesis.

PMID- 24043335
TI  - Pathological findings in enucleated eyes after intravitreal melphalan injection.
AB  - The aim of this study is to evaluate the pathological findings of the eye after
      intravitreal melphalan for viable vitreous seeding from retinoblastoma. All
      enucleated eyes receiving an intravitreal injection of melphalan (10-50 MUg in
      0.05 cc) were evaluated for histological changes. Of 25 treated cases, 8 eyes
      needed enucleation because of phthisis, parent request, or new tumor development.
      One of the cases was excluded from the study because of a history of intra
      arterial chemotherapy with melphalan. There was no case of needle-site scleral
      involvement by retinoblastoma cells. In two eyes receiving 50 MUg melphalan, no
      viable retinoblastoma cell was detectable in the eye. Severe gliosis, vascular
      occlusion, retinal necrosis, hemorrhage and neovascularization were seen.
      Histologically, intravitreal melphalan for recalcitrant or recurrent vitreous
      seeds from retinoblastoma appears to provide acceptable vitreous seed control. It
      seems that higher doses could be destructive causing ischemic necrosis in the
      retina, severe gliosis and secondary neovascular changes as well as having a
      destructive effect on retinoblastoma cells.

PMID- 24043334
TI  - Myopia onset and progression: can it be prevented?
AB  - Myopia is the commonest ocular abnormality and the high and growing prevalence of
      myopia, especially but not only in Asian populations, as well as its progressive
      nature in children, has contributed to a recent surge in interest. Such worldwide
      growing prevalence seems to be associated with increasing educational pressures,
      combined with life-style changes, which have reduced the time that children spend
      outdoors. Highly nearsighted people are at greater risk for several vision
      threatening problems such as retinal detachments, choroidal neovascularization,
      cataracts and glaucoma, thus the potential benefits of interventions that can
      limit or prevent myopia progression would be of remarkable social impact. Our
      understanding of the regulatory processes that lead an eye to refractive errors
      is undoubtedly incomplete but has grown enormously in the last decades thanks to
      the animal studies, observational clinical studies, and randomized clinical
      trials recently published. In this review we assess the effects of several types
      of life-style and interventions, including outdoor activities, eye drops,
      undercorrection of myopia, multifocal spectacles, contact lenses, and refractive
      surgery on the onset and progression of nearsightedness. 

PMID- 24043336
TI  - Early results of stand-alone anterior lumbar interbody fusion in iatrogenic
      spondylolisthesis patients.
AB  - BACKGROUND: Iatrogenic spondylolisthesis is a challenging condition for spinal
      surgeons. Posterior surgery in these cases is complicated by poor anatomical
      landmarks, scar tissue adhesion of muscle and dural structures and difficult
      access to the intervertebral disc. Anterior interbody fusion provides an
      alternative treatment method, allowing indirect foraminal decompression, reliable
      disc clearance and implantation of large surface area implants. MATERIALS AND
      METHODS: A retrospective chart review of patients with iatrogenic
      spondylolisthesis including pre- and post-operative Oswestry Disability Index
      (ODI) and Visual Analogue Scale (VAS) scores was performed. Imaging criteria were
      pelvic incidence, overall lumbar lordosis and segmental lordosis. In addition,
      the fusion rate was investigated after 6 months. RESULTS: Six consecutive
      patients treated between 2008 and 2011 (4 female, 2 male, mean age 61 +/- 7.1
      years) were identified. The initially performed surgeries included decompression
      with or without discectomy; posterior instrumented and non-instrumented fusion.
      The olisthetic level was in all cases at the decompressed level. All patients
      were revised with stand-alone anterior interbody fusion devices at the olisthetic
      level filled with BMP 2. Average ODI dropped from 49 +/- 11 % pre-operatively to
      26.0 +/- 4.0 at 24 months follow-up. VAS average dropped from 7 +/- 1 to 2 +/- 0.
      Mean total lordosis of 39.8 +/- 2.8 degrees  increased to 48.5 +/- 4.9 degrees 
      at pelvic incidences of 48.8 +/- 6.8 degrees  pre-operatively. Mean segmental
      lordosis at L4/5 improved from 10.5 +/- 6.7 degrees  to 19.0 +/- 4.9 degrees  at
      24 months. Mean segmental lordosis in L5/S1 increased from 15.1 +/- 7.4 degrees 
      to 23.2 +/- 5.6 degrees . Cage subsidence due to severe osteoporosis occurred in
      one case after 5 months, and hence there was no further follow-up. Fusion was
      confirmed in all other patients. CONCLUSION: Anterior interbody fusion offers
      good stabilisation and restoration of lordosis in iatrogenic spondylolisthesis
      and avoids the well-known problems associated with reentering the spinal canal
      for revision fusions. In this group, ODI and VAS scores were improved.

PMID- 24043337
TI  - Which factors prognosticate rotational instability following lumbar laminectomy?
AB  - PURPOSE: Reduced strength and stiffness of lumbar spinal motion segments
      following laminectomy may lead to instability. Factors that predict shear
      biomechanical properties of the lumbar spine were previously published. The
      purpose of the present study was to predict spinal torsion biomechanical
      properties with and without laminectomy from a total of 21 imaging parameters.
      METHOD: Radiographs and MRI of ten human cadaveric lumbar spines (mean age 75.5,
      range 59-88 years) were obtained to quantify geometry and degeneration of the
      motion segments. Additionally, dual X-ray absorptiometry (DXA) scans were
      performed to measure bone mineral content and density. Facet-sparing lumbar
      laminectomy was performed either on L2 or L4. Spinal motion segments were
      dissected (L2-L3 and L4-L5) and tested in torsion, under 1,600 N axial
      compression. Torsion moment to failure (TMF), early torsion stiffness (ETS, at 20
      40 % TMF) and late torsion stiffness (LTS, at 60-80 % TMF) were determined and
      bivariate correlations with all parameters were established. For dichotomized
      parameters, independent-sample t tests were used. RESULTS: Univariate analyses
      showed that a range of geometric characteristics and disc and bone quality
      parameters were associated with torsion biomechanical properties of lumbar
      segments. Multivariate models showed that ETS, LTS and TMF could be predicted for
      segments without laminectomy (r (2) values 0.693, 0.610 and 0.452, respectively)
      and with laminectomy (r (2) values 0.952, 0.871 and 0.932, respectively), with
      DXA-derived measures of bone quality and quantity as the main predictors.
      CONCLUSIONS: Vertebral bone content and geometry, i.e. intervertebral disc width,
      frontal area and facet joint tropism, were found to be strong predictors of ETS,
      LTS and TMF following laminectomy, suggesting that these variables could predict
      the possible development of post-operative rotational instability following
      lumbar laminectomy. Proposed diagnostic parameters might aid surgical decision
      making when deciding upon the use of instrumentation techniques.

PMID- 24043338
TI  - Relation between radiological assessment and biomechanical stability of lumbar
      interbody fusion in a large animal model.
AB  - PURPOSE: To relate the progress of vertebral segmental stability after interbody
      fusion surgery with radiological assessment of spinal fusion. METHODS: Twenty
      goats received double-level interbody fusion and were followed for a period of 3,
      6 and 12 months. After killing, interbody fusion was assessed radiographically by
      two independent observers. Subsequently, the lumbar spines were subjected to four
      point bending and rotational deformation, assessed with an optoelectronic 3D
      movement registration system. In addition, four caprine lumbar spines were
      analysed in both the native situation and after the insertion of a cage device,
      as to mimic the direct post-surgical situation. The range of motion (ROM) in
      flexion/extension, lateral bending and axial rotation was analysed ex vivo using
      a multi-segment testing system. RESULTS: Significant reduction in ROM in the
      operated segments was already achieved with moderate bone ingrowth in
      flexion/extension (71 % reduction in ROM) and with only limited bone ingrowth in
      lateral bending (71 % reduction in ROM) compared to the post-surgical situation.
      The presence of a sentinel sign always resulted in a stable vertebral segment in
      both flexion/extension and lateral bending. For axial rotation, the ROM was
      already limited in both native and cage inserted situations, resulting in non
      significant differences for all radiographic scores. DISCUSSION: In vivo
      vertebral segment stability, defined as a significant reduction in ROM, is
      achieved in an early stage of spinal fusion, well before a radiological bony
      fusion between the vertebrae can be observed. Therefore, plain radiography
      underestimates vertebral segment stability.

PMID- 24043339
TI  - Percutaneous pedicle screw fixation in polytrauma patients.
AB  - PURPOSE: The clinical outcome of polytrauma patients underwent spine fixation was
      analyzed and correlated both to surgical time (early versus delayed) and to
      fixation type (open versus percutaneous). METHODS: Twenty-four polytrauma
      patients were retrospectively evaluated. Patients were evaluated according to
      age, accident dynamic, mechanical ventilation need, blood transfusion need, SAPS
      II score, type of vertebral injury, time of fixation (within or after 72 h) and
      type of fixation. RESULTS: Nine patients underwent percutaneous pedicle screw
      fixation and 12 open fusion. An early fixation allows better clinical outcome
      considering ICU stay (13.7 versus 21.71 days), H-LOS (25.8 versus 69.5 days),
      mechanical ventilation need (7 versus 16.2), blood transfusion need (250 versus
      592 cc). CONCLUSIONS: In polytrauma patients an early spine fixation improves
      clinical outcome. Patients underwent percutaneous screw fixation showed a better
      outcome compared to open surgery group obtained despite worst clinical
      conditions.

PMID- 24043340
TI  - Occipito-cervical fusion in post-traumatic instability of the upper cervical
      spine and cranio-cervical junction.
AB  - INTRODUCTION: Surgical management of upper cervical spine (UCS) unstable injuries
      may be challenging as the number of cases requiring this surgery collected in
      every single center is small. This retrospective study was conducted to analyze
      the radiographic and clinical results in 12 patients undergoing a posterior
      occipito-cervical fusion by a polyaxial screws-rod-plate system. METHODS: There
      were eight male and four female patients with a mean age of 73.7 years (range 32
      89 years). Six patients presented neurologic deficits at admission. Six patients
      had sustained major trauma. The remaining six patients had suffered a minor
      trauma. RESULTS: Two patients died postoperatively in Intensive Care Unit. All
      surviving patients achieved solid fusion at 6 months. No surviving patient had
      neurological deterioration postoperatively. There were no instrumentation
      failures or revision required. Two patients suffered from superficial occipital
      wound infection. CONCLUSIONS: Although the indication to occipito-cervical fusion
      decreased since the new C1-C2 posterior fixation techniques were described, it
      remains a valid and reliable option in UCS post-traumatic instability to be
      applied even in emergency especially in the elderly.

PMID- 24043341
TI  - Cheneau brace for adolescent idiopathic scoliosis: long-term results. Can it
      prevent surgery?
AB  - OBJECTIVE: The aim of this study was to evaluate the effectiveness of Cheneau
      brace in the management of idiopathic scoliosis. METHODS: This is a retrospective
      observational study according to SOSORT and SRS (Scoliosis Research Society)
      recommendations involving 48 girls with documented progressive idiopathic
      scoliosis, treated with Cheneau brace. A statistical analysis was performed with
      STATA MP11.2 to validate the obtained results. RESULTS: No patient needed
      surgery. The average curve angle measured in Cobb degrees passed from 27 degrees 
      +/- 6.7 degrees  at the beginning (T0), to 7.6 degrees  +/- 7.4 degrees  in brace
      (T1) (72 % of correction), to 8.5 degrees  +/- 8.6 degrees  (69 % of correction)
      at the end of treatment (T2), to 11.0 degrees  +/- 7.4 degrees  (59.3 % of
      correction) at final follow-up (mean 5 years and 5 months) (T3). CONCLUSION:
      Conservative treatment with Cheneau brace and physiotherapy was effective in our
      hands for halting scoliosis progression in 100 % of patients.

PMID- 24043342
TI  - Combination of current-integrating/photon-counting detector modules for spectral
      CT.
AB  - Inspired by compressive sensing theory and spectral detection technology, here we
      propose a novel design of a CT detector array that uses current
      integrating/photon-counting modules in an interlacing fashion so that strengths
      of each detector type can be synergistically combined. For geometrical symmetry,
      an evenly alternating pattern is initially assumed for these detector modules to
      form a hybrid detector array. While grayscale detector modules acquire regular
      raw data in a large dynamic range cost-effectively, spectral detector modules
      simultaneously sense energy-discriminative data in multiple energy bins. A split
      Bregman iterative algorithm is developed for spectral CT reconstruction from
      projection data of an object collected with the hybrid detector array. With
      mathematical phantoms, an optimal ratio of the number of the spectral elements
      over the number of grayscale elements is determined based on classic image
      quality evaluation. This hybrid detector array is capable of delivering a
      performance comparable with that of a full spectral detector array. 

PMID- 24043343
TI  - The energy flux theory 35 years later: formulations and applications.
AB  - Several models have been proposed for the energetic behavior of the
      photosynthetic apparatus and a variety of experimental techniques are nowadays
      available to determine parameters that can quantify this behavior. The Energy
      Flux Theory (EFT) developed by Strasser 35 years ago provides a straightforward
      way to formulate any possible energetic communication between any complex
      arrangement of interconnected pigment systems and any energy transduction by
      these systems. We here revisit the EFT, starting from the basic general
      definitions and equations and presenting applications in formulating the energy
      distribution in photosystem (PS) II units with variable connectivity, as
      originally derived, where certain simplifications were adopted. We then proceed
      to the derivation of equations for a PSII model of higher complexity, which
      corresponds, from the formalistic point of view, to the later formulated and now
      broadly accepted exciton-radical-pair model. We also compare the formulations
      derived with the EFT with those obtained, by different approaches, in the classic
      papers on energetic connectivity. Moreover, we apply the EFT for the evaluation
      of the excitation energy distribution between PSII and PSI and the distinction
      between state transitions and PSII to PSI excitation energy migration. Our
      analysis demonstrates that the EFT is a powerful approach for the formulation of
      any possible model, at any complexity level, even of models that may be proposed
      in the future, with the advantage that any possible energetic communication or
      energy transduction can be easily formulated mathematically by trivial algebraic
      equations. Moreover, the biophysical parameters introduced by the EFT and
      applicable for any possible model can be linked with obtainable experimental
      signals, provided that the theoretical resolution of the model does not go beyond
      the experimental resolution. 

PMID- 24043344
TI  - The effects of an acute challenge with the NMDA receptor antagonists, MK-801,
      PEAQX, and ifenprodil, on social inhibition in adolescent and adult male rats.
AB  - RATIONALE: NMDA antagonists consistently produce social inhibition in adult
      animals, although effects of these manipulations on social behavior of
      adolescents are relatively unknown. OBJECTIVES: The aim of this study was to
      assess potential age differences in the socially inhibitory effects of the non
      competitive NMDA antagonist, MK-801, as well as NR2 subunit selective effects,
      given the regional and developmental differences that exist for the NR2 subunit
      during ontogeny. METHODS: In separate experiments, adolescent and adult male
      Sprague-Dawley rats were treated acutely with MK-801 (0, 0.05, 0.1, 0.2 mg/kg,
      i.p.), the NR2A antagonist, PEAQX (2.5, 5, 10, 20 mg/kg, s.c.), or the NR2B
      antagonist, ifenprodil (1.5, 3, 6, 12 mg/kg, i.p.), 10 min prior to a social
      interaction test. RESULTS: Adolescents required higher doses of MK-801 (0.1 and
      0.2 mg/kg) to induce social suppression, whereas adults demonstrated reductions
      in social activity after all doses. Likewise, adolescents required higher doses
      of ifenprodil (6 and 12 mg/kg) to produce social inhibitory effects relative to
      adults (all doses). In contrast, adults were less sensitive to PEAQX than
      adolescents, with adults showing social inhibition after 20 mg/kg whereas
      adolescents showed this effect following 10 and 20 mg/kg. Although locomotor
      activity was generally reduced at both ages by all drugs tested, ANCOVAs using
      locomotor activity as a covariate revealed similar patterns of social inhibitory
      effects. CONCLUSIONS: Adolescents are less sensitive than adults to the
      disruption of social behavior by NMDA and NR2B-selective receptor antagonism, but
      not by an NR2A antagonist-age differences that may be related to different
      subunit expression patterns during development.

PMID- 24043347
TI  - Exploring the perspectives of obese adolescent girls.
AB  - To understand obese adolescent girls' perspectives regarding their weight and
      health we studied video intervention/prevention assessment audiovisual narratives
      created by 14 obese girls ages 12 to 20 years. The narratives included
      interviews, monologues, and daily activities. Themes included illness
      conceptualizations, health concerns, health misinformation, and distress
      regarding appearance deriving from both within and without. The predominant theme
      was ambivalence about obesity. Close examination of these themes revealed
      potential footholds for intervention. Sensitive exploration of issues such as
      appearance and psychosocial distress might strengthen the patient-clinician
      partnership in identifying a patient's strengths and motivating weight loss. 

PMID- 24043345
TI  - Attenuation of anticipatory nausea in a rat model of contextually elicited
      conditioned gaping by enhancement of the endocannabinoid system.
AB  - RATIONALE: Enhancement of the endocannabinoid (EC) system may reduce anticipatory
      nausea (AN). OBJECTIVES: The experiments evaluated the potential of the dual
      fatty acid amide hydrolase (FAAH)/monoacylglycerol lipase (MAGL) inhibitor,
      JZL195, on its own and combined with anandamide (AEA) and 2-arachidonoyl glycerol
      (2-AG) to reduce contextually elicited gaping, a measure of AN in rats. METHODS:
      Following four context lithium chloride (LiCl) pairings, rats were injected with
      vehicle (VEH) or JZL195 (10 mg kg(-1), intraperitoneally) 105 min before an
      injection of VEH, 2-AG (1.25 mg kg(-1)), or AEA (5.0 mg kg(-1)). Fifteen minutes
      later, all rats were placed in the LiCl-paired context for 5 min and in a
      different context for a 15-min locomotor test. Whole brains were extracted for EC
      analysis. The potential of the CB1 antagonist, SR141716, to reverse the
      suppression of AN by both JZL195 and AEA and of the CB2 antagonist, AM630, to
      reverse the suppression of AN by JZL195 was then evaluated. RESULTS: JZL195
      suppressed gaping and elevated AEA, palmitoylethanolamine, and
      oleoylethanolamide. As the suppression of gaping was reversed by SR141716, but
      not by AM630, the effect was CB1 mediated. The suppressive effect of JZL195 on
      gaping, as well as elevation of AEA and 2-AG, was amplified by pretreatment with
      either AEA or 2-AG. On its own, AEA, but not 2-AG, also suppressed gaping-an
      effect that was also prevented by CB1 antagonism. CONCLUSIONS: JZL195 reduces AN
      primarily by acting as a FAAH inhibitor, but MAGL inhibition is also indicated.

PMID- 24043348
TI  - Heterosexual gender relations in and around childhood risk and safety.
AB  - Injuries are a leading cause of child death, and safety interventions frequently
      target mothers. Fathers are largely ignored despite their increasing childcare
      involvement. In our qualitative study with 18 Canadian heterosexual couples
      parenting children 2 to 7 years old, we examined dyadic decision making and
      negotiations related to child safety and risk engagement in recreational
      activities. Parents viewed recreation as an important component of men's
      childcare, but women remained burdened with mundane tasks. Most couples perceived
      men as being more comfortable with risk than women, and three negotiation
      patterns emerged: fathers as risk experts; mothers countering fathers' risk; and
      fathers acknowledging mothers' safety concerns but persisting in risk activities.
      Our findings suggest that contemporary involved fathering practices privilege men
      in the outdoors and can erode women's control for protecting children from
      unintentional injury. We recommend promoting involved fathering that empowers
      both parents and developing injury-prevention strategies incorporating both
      fathers' and mothers' perspectives. 

PMID- 24043350
TI  - Plantar fibromatosis--topical review.
AB  - Morbus Ledderhose is a rare hyperproliferative disease of the plantar fascia,
      leading to the formation of nodules. Its origin is unknown. No causal therapy is
      available, and treatment remains symptomatic. Various therapeutic strategies to
      alleviate symptoms are available and are adapted to the severity of the disease.
      In early stages, conservative therapy including nonpharmacological, physical, and
      pharmacological treatments is applied. If the disease progresses, irradiation of
      the plantar surface, injections of steroids, shock wave therapy, and partial or
      complete fasciectomy as an ultimate therapy may be indicated. Novel experimental
      treatment options including application of fibrinolytic agents are currently
      being tested, but no controlled, randomized long-term studies are available. This
      review aims to provide a systematic overview of current established procedures
      and outlines novel experimental strategies for the treatment of morbus
      Ledderhose, including future avenues to treat this rare disease.

PMID- 24043351
TI  - Establishing the relationship between clinical outcome and extent of osseous
      bridging between computed tomography assessment in isolated hindfoot and ankle
      fusions.
AB  - BACKGROUND: Determining the success of joint fusion operations is often a
      diagnostic dilemma, and many factors may be considered. Most would agree that the
      broad categories of clinical success and radiographic success are likely most
      useful to determine the overall success of a joint fusion operation. Very little
      evidence exists to assist the surgeon in determining what constitutes a
      successful radiographic fusion. The aim of this study was to determine the extent
      of osseous bridging as measured by computed tomography (CT) that was associated
      with a good clinical outcome as measured by the 12-Item Short Form (SF-12), Foot
      Function Index (FFI), and American Orthopaedic Foot & Ankle Society (AOFAS)
      clinical outcomes questionnaires at 24 weeks. METHODS: Patients who had isolated
      joint fusions were evaluated (n = 275) to determine the correlation of extent of
      osseous bridging with clinical outcome. The extent of osseous bridging across the
      joint in question was categorized as absent (0%-24%), minimal (25%-49%) moderate
      (50%-74%), or complete (75%-100%). Clinical outcome scores included the SF-12,
      FFI, and AOFAS outcomes score. RESULTS: Patients evaluated to have at least
      minimal osseous bridging at fusion sites (25%-49%) on CT reported a clinically
      important improvement in SF-12, FFI, and AOFAS, whereas those with "absent"
      osseous bridging (0%-24%) did not report a clinically important improvement in
      outcome scores. CONCLUSION: This study suggests that osseous bridging of greater
      than 25% to 49% at the fusion site measured by CT may be necessary to consider a
      hindfoot or ankle fusion clinically successful. LEVEL OF EVIDENCE: Level IV, case
      series.

PMID- 24043352
TI  - Peritalar instability after tibiotalar fusion for valgus unstable ankle in stage
      IV adult acquired flatfoot deformity: case series.
AB  - BACKGROUND: An unstable valgus ankle with an incompetent medial ligament complex
      is still treated by many surgeons with isolated tibiotalar (TT) arthrodesis. To
      date, it is unknown whether rigid fixation of the talus within the ankle mortise
      sufficiently corrects and stabilizes the hindfoot complex. The purpose of this
      study was to critically analyze patients with this problem and to assess the
      underlying causes for their acquired peritalar instability. METHODS: This series
      included 4 male patients (ages 55, 70, 72, and 79 years). Preoperatively, all
      patients presented with an unstable valgus ankle associated with stage IV adult
      acquired flatfoot deformity (AAFD), with a valgus talar tilt averaging 12 degrees
      (ranging from 9 to 14 degrees). All patients had a successful TT fusion, with
      screws and plates used for fixation. The position of the TT fusion was estimated
      at the intersection of a line drawn defining the talar shoulders and the
      longitudinal tibial axis on the anteroposterior weight-bearing radiograph. The
      hindfoot deformity was measured via the calcaneal offset on the Saltzman view.
      RESULTS: All patients had a healed TT fusion with the talus remaining in valgus
      averaging 4.8 degrees (ranging from 4 to 6 degrees). At the latest follow-up (1.2
      18 years), all patients showed a progressive destabilization of the hindfoot
      complex that resulted in a valgus pronation deformity with flattening of the arch
      and a highly unstable foot that was not manageable with corrective shoes and
      braces. Key findings were a floppy hindfoot that turned into extreme valgus
      misalignment while loading. Radiographically, the calcaneal offset was in valgus
      misalignment of 16 to 54 mm related to the tibial axis on the Saltzman alignment
      view. In 2 cases, there was a complete medial dislocation of the talus.
      CONCLUSIONS: Even with rigid stabilization of the talus in the ankle mortise,
      peritalar instability may persist and allow calcaneus and navicular subluxation
      around the talus, which can result in progressive destabilization of the hindfoot
      complex. In stage IV AAFD, incompetent peritalar ligaments may not be able to
      withstand the increased mechanical load after TT fusion. Persistent valgus talar
      tilt after fusion may promote this unfavorable process. Therefore, isolated TT
      fusion should be performed with caution for treatment of valgus tilted ankles in
      stage IV AAFD. If this is considered, we recommend that fusion in neutral or even
      slightly varus talar positions be attempted. LEVEL OF EVIDENCE: Level IV,
      retrospective case series.

PMID- 24043353
TI  - Comparison of extramedullary versus intramedullary referencing for tibial
      component alignment in total ankle arthroplasty.
AB  - BACKGROUND: The majority of total ankle arthroplasty (TAA) systems use
      extramedullary alignment guides for tibial component placement. However, at least
      1 system offers intramedullary referencing. In total knee arthroplasty, studies
      suggest that tibial component placement is more accurate with intramedullary
      referencing. The purpose of this study was to compare the accuracy of
      extramedullary referencing with intramedullary referencing for tibial component
      placement in total ankle arthroplasty. METHODS: The coronal and sagittal tibial
      component alignment was evaluated on the postoperative weight-bearing
      anteroposterior (AP) and lateral radiographs of 236 consecutive fixed-bearing
      TAAs. Radiographs were measured blindly by 2 investigators. The postoperative
      alignment of the prosthesis was compared with the surgeon's intended alignment in
      both planes. The accuracy of tibial component alignment was compared between the
      extramedullary and intramedullary referencing techniques using unpaired t tests.
      Interrater and intrarater reliabilities were assessed with intraclass correlation
      coefficients (ICCs). RESULTS: Eighty-three tibial components placed with an
      extramedullary referencing technique were compared with 153 implants placed with
      an intramedullary referencing technique. The accuracy of the extramedullary
      referencing was within a mean of 1.5 +/- 1.4 degrees and 4.1 +/- 2.9 degrees in
      the coronal and sagittal planes, respectively. The accuracy of intramedullary
      referencing was within a mean of 1.4 +/- 1.1 degrees and 2.5 +/- 1.8 degrees in
      the coronal and sagittal planes, respectively. There was a significant difference
      (P < .001) between the 2 techniques with respect to the sagittal plane alignment.
      Interrater ICCs for coronal and sagittal alignment were high (0.81 and 0.94,
      respectively). Intrarater ICCs for coronal and sagittal alignment were high for
      both investigators. CONCLUSIONS: Initial sagittal plane tibial component
      alignment was notably more accurate when intramedullary referencing was used.
      Further studies are needed to determine the effect of this difference on clinical
      outcomes and long-term survivability of the implants. LEVEL OF EVIDENCE: Level
      III, retrospective comparative study.

PMID- 24043354
TI  - Kv1.3 inhibitors have differential effects on glucose uptake and AMPK activity in
      skeletal muscle cell lines and mouse ex vivo skeletal muscle.
AB  - Knockout of Kv1.3 improves glucose homeostasis and confers resistance to obesity.
      Additionally, Kv1.3 inhibition enhances glucose uptake. This is thought to occur
      through calcium release. Kv1.3 inhibition in T-lymphocytes alters mitochondrial
      membrane potential, and, as many agents that induce Ca(2+) release or inhibit
      mitochondrial function activate AMPK, we hypothesised that Kv1.3 inhibition would
      activate AMPK and increase glucose uptake. We screened cultured muscle with a
      range of Kv1.3 inhibitors for their ability to alter glucose uptake. Only Psora4
      increased glucose uptake in C2C12 myotubes. None of the inhibitors had any impact
      on L6 myotubes. Magratoxin activated AMPK in C2C12 myotubes and only Pap1
      activated AMPK in the SOL. Kv1.3 inhibitors did not alter cellular respiration,
      indicating a lack of effect on mitochondrial function. In conclusion, AMPK does
      not mediate the effects of Kv1.3 inhibitors and they display differential effects
      in different skeletal muscle cell lines without impairing mitochondrial function.

PMID- 24043355
TI  - MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes
      via a mitochondrial apoptotic pathway.
AB  - Myocardial ischemia reperfusion (I/R) can induce altered expression of microRNAs
      (miRNAs). The miRNAs-miR-15a, miR-15b and miR-16 have been shown to play a role
      in apoptosis, although not in cardiac-related models. We investigated the roles
      of miR-15b in hypoxia/reoxygenation (H/R)-induced apoptosis of cardiomyocytes.
      Quantitative real time polymerase chain reaction results showed that the
      expression of miR-15a and miR-15b were up-regulated in Sprague-Dawley rat hearts
      subjected to I/R. Expression levels of miR-15b increased more than four fold
      above basal levels. Similar results were obtained for cardiomyocytes exposed to
      H/R. Recombinant adenoviral vectors were generated to explore the functional role
      of miR-15b in cultured cardiomyocytes exposed to H/R. Overexpression of miR-15b
      enhanced cell apoptosis and the loss of mitochondrial membrane potential, as
      determined by flow cytometric analysis. Conversely, down-regulated expression was
      cytoprotective. The effects of miR-15b can by mimicked by Bcl-2 short-interfering
      RNAs. The inhibition of miR-15b increased expression levels of the Bcl-2 protein
      without affecting Bcl-2 mRNA levels, suppressed the release of mitochondrial
      cytochrome c to the cytosol and decreased the activities of caspase-3 and 9. It
      is possible that miR-15b is the upstream regulator of a mitochondrial signaling
      pathway for H/R induced apoptosis. 

PMID- 24043356
TI  - Family ties and health cross-nationally: the contextualizing role of familistic
      culture and public pension spending in Europe.
AB  - OBJECTIVES: Although previous research theorizes that cross-national variation in
      the relationship between family ties and health is due to nation-level
      differences in culture and policy/economics, no study has examined this
      theorization empirically. METHOD: Using data from the Survey of Health, Ageing,
      and Retirement in Europe (SHARE) and the Organization for Economic Co-operation
      and Development (OECD), this study uses multilevel modeling to analyze individual
      , nation-, and cross-level effects for 30,291 older adults in 14 nations.
      RESULTS: Family ties to spouses/partners and parents are associated with better
      health, but ties to coresident children are associated with poorer health in
      certain contexts. Familistic culture and public pension spending have a weak but
      statistically significant moderating effect on the relationship between
      intergenerational family ties and health. DISCUSSION: This article underscores
      the complexity of family and highlights the need for continued theorization and
      measurement at the nation level to promote older adults' health in diverse
      contexts.

PMID- 24043357
TI  - Exploring the mammalian sensory space: co-operations and trade-offs among senses.
AB  - The evolution of a particular sensory organ is often discussed with no
      consideration of the roles played by other senses. Here, we treat mammalian
      vision, olfaction and hearing as an interconnected whole, a three-dimensional
      sensory space, evolving in response to ecological challenges. Until now, there
      has been no quantitative method for estimating how much a particular animal
      invests in its different senses. We propose an anatomical measure based on
      sensory organ sizes. Dimensions of functional importance are defined and
      measured, and normalized in relation to animal mass. For 119 taxonomically and
      ecologically diverse species, we can define the position of the species in a
      three-dimensional sensory space. Thus, we can ask questions related to possible
      trade-off vs. co-operation among senses. More generally, our method allows
      morphologists to identify sensory organ combinations that are characteristic of
      particular ecological niches. After normalization for animal size, we note that
      arboreal mammals tend to have larger eyes and smaller noses than terrestrial
      mammals. On the other hand, we observe a strong correlation between eyes and
      ears, indicating that co-operation between vision and hearing is a general
      mammalian feature. For some groups of mammals we note a correlation, and possible
      co-operation between olfaction and whiskers. 

PMID- 24043359
TI  - Removing sensory input disrupts spinal locomotor activity in the early postnatal
      period.
AB  - Motor patterns driving rhythmic movements of our lower limbs during walking are
      generated by groups of neurons within the spinal cord, called central pattern
      generators (CPGs). After suffering a spinal cord injury (SCI), many descending
      fibers from our brain are severed or become nonfunctional, leaving the spinal CPG
      network without its initiating drive. Recent studies have focused on the
      importance of maintaining sensory stimulation to the limbs of SCI patients as a
      way to initiate and control the CPG locomotor network. We began assessing the
      role of sensory feedback to the locomotor CPG network using a neonatal mouse
      spinal cord preparation where the hindlimbs are still attached. Removing sensory
      feedback coming from the hindlimbs by way of a lower lumbar transection or by
      ventral root denervation revealed a positive correlation in the ability of
      sensory input deprivation to disrupt ongoing locomotor activity on older versus
      younger animals. The differences in the motor responses as a function of age
      could be correlated with the loss of excitatory activity from sensory afferents.
      Continued studies on this field could eventually provide key information that
      translates into the design of novel therapeutic strategies to treat patients who
      have suffered a SCI. 

PMID- 24043358
TI  - Aggression and courtship in Drosophila: pheromonal communication and sex
      recognition.
AB  - Upon encountering a conspecific in the wild, males have to rapidly detect,
      integrate and process the most relevant signals to evoke an appropriate
      behavioral response. Courtship and aggression are the most important social
      behaviors in nature for procreation and survival: for males, making the right
      choice between the two depends on the ability to identify the sex of the other
      individual. In flies as in most species, males court females and attack other
      males. Although many sensory modalities are involved in sex recognition,
      chemosensory communication mediated by specific molecules that serve as
      pheromones plays a key role in helping males distinguish between courtship and
      aggression targets. The chemosensory signals used by flies include volatile and
      non-volatile compounds, detected by the olfactory and gustatory systems.
      Recently, several putative olfactory and gustatory receptors have been identified
      that play key roles in sex recognition, allowing investigators to begin to map
      the neuronal circuits that convey this sensory information to higher processing
      centers in the brain. Here, we describe how Drosophila melanogaster males use
      taste and smell to make correct behavioral choices. 

PMID- 24043360
TI  - Depressive symptoms following coping with peer aggression: the moderating role of
      negative emotionality.
AB  - The way in which children cope with peer aggression may determine their
      subsequent adjustment, but different forms of coping may be more or less
      effective for particular children. This research examined whether the
      contribution of children's coping to subsequent depressive symptoms was
      contingent on children's temperament (i.e., level of negative emotionality; NE)
      and gender. Children (N = 235, 102 boys, 133 girls, M = 7.94 years, SD = 0.33)
      reported on exposure to peer victimization. Parents rated children's NE and
      depressive symptoms, and teachers rated children's coping. For girls with high
      NE, problem solving protected against depressive symptoms whereas seeking
      retaliation heightened risk for depressive symptoms. Advice seeking protected
      children with low NE against depressive symptoms whereas ignoring protected
      children with high NE against depressive symptoms. Humor predicted fewer
      depressive symptoms in boys with high NE but more depressive symptoms in boys
      with low NE. This research helps to elucidate individual differences in the
      effects of coping on adjustment, and has implications for interventions aimed at
      reducing risk resulting from exposure to peer aggression. 

PMID- 24043361
TI  - Second-generation tyrosine kinase inhibitors in first-line treatment of chronic
      myeloid leukaemia (CML).
AB  - Tyrosine kinase inhibitors (TKIs) have contributed to marked improvements in
      survival in patients with chronic myeloid leukaemia (CML). This article discusses
      the place of the second-generation TKIs dasatinib and nilotinib in the first-line
      treatment of CML and is based on published literature. The new agents are more
      potent and effective than imatinib. Data from pivotal clinical trials indicate
      that response to dasatinib and nilotinib is greater and more rapid than that to
      imatinib, resulting in a higher probability of patients achieving an optimal
      response to treatment. Differences between the newer agents with respect to
      patient groups for whom caution is advised, drug interaction potential,
      haematological toxicity, pulmonary toxicity, changes in the immune system and
      effects on laboratory parameters are discussed. With similar levels of efficacy,
      the choice of second-generation agents should be guided by the characteristics of
      the individual patient and the most suitable dosing regimen. 

PMID- 24043362
TI  - CD30 as a therapeutic target for lymphoma.
AB  - Hodgkin's lymphoma (HL) and ALK(+) anaplastic large-cell lymphoma (ALCL) have
      become highly curable due to the success of modern regimens of chemotherapy and
      radiotherapy. However, up to one-third of the patients experience relapse or do
      not respond to first-line therapy, and half of them relapse again after secondary
      therapy with limited options for further treatment. In the last 15 years,
      monoclonal antibodies (mAbs) directed to surface receptors became a new and
      valuable therapeutic option in many hematologic malignancies. Due to its
      restricted expression on normal activated lymphocytes and its high expression on
      malignant cells, CD30 represents an attractive target molecule for HL and ALCL
      therapy. However, unconjugated CD30 mAbs have demonstrated a lack of objective
      clinical responses in patients with recurrent HL. CD30 exhibits complex signaling
      pathways, and binding of its natural ligand or anti-CD30 mAbs can induce
      apoptosis but may also promote proliferation and activation depending on the
      cellular context. Moreover, CD30 rapidly internalizes after crosslinking, which
      counteracts efficient recruitment of immunologic effectors but also provides the
      opportunity to transfer cytotoxic payloads coupled to CD30-specific mAbs into the
      tumor cells. Several tumor targeting approaches have been studied, including
      radio-immunoconjugates, immunotoxins, immunoRNases, immunokinases, and antibody
      drug conjugates (ADCs). In 2011, the ADC brentuximab-vedotin, consisting of the
      CD30-specific chimeric mAb cAC10 and the potent tubulin toxin monomethyl
      auristatin E, gained regulatory approval as a well tolerated and highly active
      drug in patients with refractory and relapsed HL and ALCL. SGN-35 is on the way
      to being incorporated in the standard management of CD30(+) lymphoma with
      significant therapeutic impact. This review gives a critical overview about anti
      CD30 therapies with unconjugated, engineered, and conjugated mAbs and the
      therapeutic challenges of treatment of CD30(+) lymphoma. 

PMID- 24043363
TI  - A method of setting limits for the purpose of quality assurance.
AB  - The result from any assurance measurement needs to be checked against some limits
      for acceptability. There are two types of limits; those that define clinical
      acceptability (action limits) and those that are meant to serve as a warning that
      the measurement is close to the action limits (tolerance limits). Currently,
      there is no standard procedure to set these limits. In this work, we propose an
      operational procedure to set tolerance limits and action limits. The approach to
      establish the limits is based on techniques of quality engineering using control
      charts and a process capability index. The method is different for tolerance
      limits and action limits with action limits being categorized into those that are
      specified and unspecified. The procedure is to first ensure process control using
      the I-MR control charts. Then, the tolerance limits are set equal to the control
      chart limits on the I chart. Action limits are determined using the Cpm process
      capability index with the requirements that the process must be in-control. The
      limits from the proposed procedure are compared to an existing or conventional
      method. Four examples are investigated: two of volumetric modulated arc therapy
      (VMAT) point dose quality assurance (QA) and two of routine linear accelerator
      output QA. The tolerance limits range from about 6% larger to 9% smaller than
      conventional action limits for VMAT QA cases. For the linac output QA, tolerance
      limits are about 60% smaller than conventional action limits. The operational
      procedure describe in this work is based on established quality management tools
      and will provide a systematic guide to set up tolerance and action limits for
      different equipment and processes. 

PMID- 24043366
TI  - Dual electroretinogram/nitric oxide carbon fiber microelectrode for direct
      measurement of nitric oxide in the in vivo retina.
AB  - Nitric oxide (NO) plays an important physiological role in normal and
      pathological retinas. Intraretinal NO concentrations have not been directly
      measured due to lack of NO electrodes capable of determining their location in
      the retina. The microelectrodes described here allow recording of the
      intraretinal electroretinogram (ERG) and NO concentration from the same location,
      with ERGs used to determine retinal depth. Double-barreled electrodes were
      constructed with one barrel serving as a reference/voltage recording barrel and
      the other containing a Nafion-coated carbon fiber used to detect NO
      amperometrically. Nafion coating imparted a high selectivity for NO versus
      ascorbic acid (2000:1). In vivo rodent experiments demonstrated that the
      electrodes could record intraretinal ERGs and NO current with minimal retinal
      thickness deformation (9%), allowing for retinal NO depth profile measurements.
      Comparison of NO depth profiles under control conditions and under nitric oxide
      synthase (NOS) inhibition by 5 mM L-NG-Nitroarginine methyl ester (L-NAME)
      verified that the recorded current was attributable to NO. NO concentrations from
      control profiles ( n = 4) were 2.37 +/- 0.34 MUM at the choroid and 1.12 +/- 0.14
      MUM at the retinal surface. NO concentrations from L-NAME profiles ( n = 4) were
      significantly lower at 0.83 +/- 0.15 MUM at the choroid ( p = 0.006) and 0.27 +/-
      0.04 MUM at the retinal surface ( p = 0.001). Localized regions of increased NO
      (100-400 nM) were seen in the inner retina under control conditions but not after
      L-NAME. The dual ERG-NO electrode may be a valuable tool in evaluating the role
      of NO in normal and diseased retinas. 

PMID- 24043365
TI  - Improved Sensing Pulses for Increased Human Head Depth Measurement Sensitivity
      With Electrical Impedance Spectroscopy.
AB  - This paper describes an improved electrical impedance spectroscopy (EIS) stimulus
      paradigm, based on dual-energy pulses using the stochastic Gabor function (SGF)
      that may more sensitively assess deep brain tissue impedance than current single
      pulse paradigms. The SGF is a uniformly distributed noise, modulated by a
      Gaussian envelope, with a wide-frequency spectrum representation regardless of
      the stimuli energy, and is least compact in the sample frequency phase plane.
      Numerical results obtained using a realistic human head model confirm that two
      sequential SGF pulses at different energies can improve EIS depth sensitivity
      when used in a dual-energy subtraction scheme. Specifically, although the two SGF
      pulses exhibit different tissue current distributions, they maintain the
      broadband sensing pulse characteristics needed to generate all the frequencies of
      interest. Moreover, finite-difference time domain simulations show that this dual
      energy excitation scheme is capable of reducing the amplitude of weighted current
      densities surface directly underneath the electrodes by approximately 3 million
      times versus single stimulation pulses, while maintaining an acceptable tissue
      conductivity distribution at depth. This increased sensitivity for the detection
      of small, deep impedance changes might be of value in potential future EIS
      applications, such as the portable, point-of-care detection of deep brain
      hemorrhage or infarction. 

PMID- 24043367
TI  - Cementless total knee arthroplasty in chronic inflammatory rheumatism.
AB  - INTRODUCTION: We report a short-term monocentric retrospective evaluation of
      cementless total knee arthroplasty (TKA) in a population suffering from chronic
      inflammatory rheumatism. MATERIALS AND METHODS: We have reviewed 23 patients (34
      knees) with an average age of 55 years (range 26-78), bearing a TKA for chronic
      inflammatory rheumatisms with a 6-year follow-up (range 3-12); 78% suffered from
      rheumatoid arthritis and 15% from juvenile rheumatoid arthritis. We used a
      cementless total prosthesis sacrificing the posterior cruciate ligament and
      bearing an ultra-congruent rotational tibial insert, the Natural Knee (NK2TM)
      (Zimmer((r)), Warsaw, IN, USA). At last follow-up, an independent surgeon
      performed a clinical assessment for pain, function and quality of life using
      International Knee Documentation Committee score, International Knee Society
      (IKS) score and Devane's score. A radiographic study evaluated secondary fixation
      according to the radiographic index of the Knee Society and according to Ewald's
      score. RESULTS: The mean postoperative IKS score was 83 points (range 40-100) for
      the knee score and 74 points (range 20-100) for the function score. Radiographic
      assessment came across only one case of loosening, concerning the tibial
      component on an asymptomatic patient. We came across the following complications:
      1 early infection, 2 important postoperative flessum deformity having needed an
      arthrolysis, 1 supracondylar fracture of the femur and 1 fracture of the patellar
      component. Survival rate at 6-year follow-up is 97% taking into account one case
      of revision. CONCLUSION: Non-cementation of this implant in chronic inflammatory
      rheumatism does not result in a higher rate of loosening. In this series,
      patients own satisfaction, function of the knee and survival rate are rather
      good. LEVEL OF EVIDENCE: Retrospective, no control group, Level IV.

PMID- 24043368
TI  - Antibiotic penetration into rabbit nucleus pulposus with discitis.
AB  - OBJECTIVE: To assess the penetration into nucleus pulposus (NP) of cephazolin and
      clindamycin in a discitis model. MATERIALS AND METHODS: Twenty New Zealand white
      rabbits were inoculated with 103 Staphylococcus aureus at lumbar disc space. The
      rabbits with discitis confirmed by MRI 10 days after inoculation were divided
      into two groups. One was given cephazolin by intravenous (IV) at 80 mg/kg/day at
      1.5 h interval for 5 half-lives; the other was given clindamycin by IV at 30
      mg/kg/day at 2.5-h interval for 5 half-lives. Thirty minutes after completion of
      the last dose, NP and serum were sent to measure antibiotic concentration.
      RESULTS: Two rabbits died during inoculation. After 10 days, 18 rabbits were
      confirmed discitis in the inoculated levels. The cephazolin and clindamycin can
      diffuse throughout the infected, sham-infected and normal NP. The serum
      concentration of cephazolin and clindamycin was 251.3 +/- 40.5 and 21.6 +/- 4.71
      mg/l, respectively. The cephazolin concentration in infected NP (1.93 +/- 0.84
      mg/l) was higher than that in sham-infected (1.73 +/- 0.61 mg/l) and normal NP
      (1.68 +/- 0.65 mg/l), but the difference showed no statistically significant (P >
      0.05). The cephazolin penetration into NP averaged 0.68-0.77 % of serum level.
      The clindamycin concentration in infected NP (4.32 +/- 1.54 mg/l) was higher than
      that in sham-infected NP (2.63 +/- 1.26 mg/l) and normal NP (2.59 +/- 1.01 mg/l)
      (P < 0.05). The penetration into NP averaged 11.9-20 % of serum level. There was
      no significance difference between sham-infected and normal NP in clindamycin and
      cephazolin concentration (P > 0.05). CONCLUSIONS: This study demonstrates
      cephazolin and clindamycin can penetrate the infected and normal NP. The
      antibiotics charge influences the delivery. Furthermore, infection condition
      selectively promotes antibiotic distribution within NP.

PMID- 24043369
TI  - Three-dimensional analyses of proximal humeral fractures using computed
      tomography with multiplanar reconstruction: early stability of fixation after
      osteosynthesis in relation to preoperative bone quality.
AB  - The purpose of this study was to evaluate the relationship between the bone
      quality of the humeral head measured by CT multiplanar reconstruction images
      (MPR) and the stability of nail or plate fixation and to compare the clinical
      outcomes of these procedures in patients with proximal humeral fractures. Thirty
      six consecutive patients (nail group: n = 18, plate group: n = 18) were
      investigated. In nail group, 14 cases were classified as two-part fractures,
      three cases were classified as three-part fractures and one case was classified
      as four-part fractures. In plate group, three cases were classified as two-part
      fractures, nine cases were classified as three-part fractures and six cases were
      classified as four-part fractures. Both clinical and radiological outcomes were
      assessed. In addition, the percentage of trabecular bone volume of the humeral
      head was calculated using preoperative CT-MPR images. Three patients in the nail
      group underwent reoperation. In contrast, no patients in the plate group
      underwent reoperation. In nail group, six of 18 (33%) patients demonstrated poor
      results (three underwent reoperation, and three had varus displacements >10o) and
      had bone volume percentages (axial image) that were significantly lower than
      those observed in the patients with good results. The cutoff point of trabecular
      bone volume required to obtain satisfactory results after surgical treatment
      using intramedullary nail was 78%. The results of this study suggest that the
      bone volume of the humeral head calculated using CT-MPR images provides useful
      information, in addition to the type of fracture, when selecting fixation devices
      for osteosynthesis of proximal humeral fracture.

PMID- 24043371
TI  - Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock.
AB  - BACKGROUND: Mortality from sepsis and septic shock remains high. Results of
      trials on intravenous immunoglobulins (IVIG) as adjunctive therapy for sepsis
      have been conflicting. This is an update of a Cochrane review that was originally
      published in 1999 and updated in 2002 and 2010. OBJECTIVES: To estimate the
      effects of IVIG as adjunctive therapy in patients with bacterial sepsis or septic
      shock on mortality, bacteriological failure rates, and duration of stay in
      hospital. SEARCH METHODS: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library 2012, Issue 6), MEDLINE (1966 to December
      2012), and EMBASE (1988 to December 2012). We contacted investigators in the
      field for unpublished data. The original search was performed in 1999 and updated
      in 2002 and 2008. SELECTION CRITERIA: We included randomized controlled trials
      comparing IVIG (monoclonal or polyclonal) with placebo or no intervention in
      patients of any age with bacterial sepsis or septic shock. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed the studies for inclusion and
      undertook methodologic quality assessment and data abstraction. We conducted pre
      specified subgroup analyses by type of immunoglobulin preparation. MAIN RESULTS:
      We included 43 studies that met our inclusion criteria in this updated review out
      of 88 potentially eligible studies. The studies included a large polyclonal IVIG
      trial in neonates that was concluded in 2011 and classified as ongoing in the
      2010 version of this review. Pooled analysis of polyclonal and monoclonal IVIG
      was not done due to clinical heterogeneity. Subgroup analysis of 10 polyclonal
      IVIG trials (n = 1430) and seven trials on IgM-enriched polyclonal IVIG (n = 528)
      showed significant reductions in mortality in adults with sepsis compared to
      placebo or no intervention (relative risk (RR) 0.81; 95% confidence interval (CI)
      0.70 to 0.93 and RR 0.66; 95% CI 0.51 to 0.85, respectively). Subgroup analysis
      of polyclonal IVIG in neonates, which now includes the recently concluded large
      polyclonal IVIG trial, showed no significant reduction in mortality for standard
      IVIG (RR 1.00; 95% CI 0.92 to 1.08; five trials, n = 3667) and IgM-enriched
      polyclonal IVIG (RR 0.57; 95% CI 0.31 to 1.04; three trials, n = 164).
      Sensitivity analysis of trials with low risk of bias showed no reduction in
      mortality with polyclonal IVIG in adults (RR 0.97; 95% CI 0.81 to 1.15; five
      trials, n = 945) and neonates (RR 1.01; 95% CI 0.93 to 1.09; three trials, n =
      3561). Mortality was not reduced among patients (eight trials, n = 4671) who
      received anti-endotoxin antibodies (RR 0.99; 95% CI 0.91 to1.06) while anti
      cytokines (nine trials, n = 7893) demonstrated a marginal reduction in mortality
      (RR 0.92; 95% CI 0.86 to 0.97). AUTHORS' CONCLUSIONS: Polyclonal IVIG reduced
      mortality among adults with sepsis but this benefit was not seen in trials with
      low risk of bias. Among neonates with sepsis, there is sufficient evidence that
      standard polyclonal IVIG, as adjunctive therapy, does not reduce mortality based
      on the inclusion of the large polyclonal IVIG trial on neonates. For Ig-M
      enriched IVIG, the trials on neonates and adults were small and the totality of
      the evidence is still insufficient to support a robust conclusion of benefit.
      Adjunctive therapy with monoclonal IVIGs remains experimental.

PMID- 24043370
TI  - Bone mineral density deficits and fractures in survivors of childhood cancer.
AB  - Although substantial increases in survival rates among children diagnosed with
      cancer have been observed in recent decades, survivors are at risk of developing
      therapy-related chronic health conditions. Among children and adolescents treated
      for cancer, acquisition of peak bone mass may be compromised by cancer therapies,
      nutritional deficiencies, and reduced physical activity. Accordingly, failure to
      accrue optimal bone mass during childhood may place survivors at increased risk
      for deficits in bone density and fracture in later life. Current recommendations
      for the treatment of bone density decrements among cancer survivors include
      dietary counseling and supplementation to ensure adequate calcium and vitamin D
      intake. Few strategies exist to prevent or treat bone loss. Moving forward,
      studies characterizing the trajectory of changes in bone density over time will
      facilitate the development of interventions and novel therapies aimed at
      minimizing bone loss among survivors of childhood cancer. 

PMID- 24043372
TI  - Tissue Cancellation in Dual Energy Mammography Using a Calibration Phantom
      Customized for Direct Mapping.
AB  - An easily implementable tissue cancellation method for dual energy mammography is
      proposed to reduce anatomical noise and enhance lesion visibility. For dual
      energy calibration, the images of an imaging object are directly mapped onto the
      images of a customized calibration phantom. Each pixel pair of the low and high
      energy images of the imaging object was compared to pixel pairs of the low and
      high energy images of the calibration phantom. The correspondence was measured by
      absolute difference between the pixel values of imaged object and those of the
      calibration phantom. Then the closest pixel pair of the calibration phantom
      images is marked and selected. After the calibration using direct mapping, the
      regions with lesion yielded different thickness from the background tissues.
      Taking advantage of the different thickness, the visibility of cancerous lesions
      was enhanced with increased contrast-to-noise ratio, depending on the size of
      lesion and breast thickness. However, some tissues near the edge of imaged object
      still remained after tissue cancellation. These remaining residuals seem to occur
      due to the heel effect, scattering, nonparallel X-ray beam geometry and Poisson
      distribution of photons. To improve its performance further, scattering and the
      heel effect should be compensated. 

PMID- 24043373
TI  - SCoRS--A Method Based on Stability for Feature Selection and Mapping
      inNeuroimaging [corrected].
AB  - Feature selection (FS) methods play two important roles in the context of
      neuroimaging based classification: potentially increase classification accuracy
      by eliminating irrelevant features from the model and facilitate interpretation
      by identifying sets of meaningful features that best discriminate the classes.
      Although the development of FS techniques specifically tuned for neuroimaging
      data is an active area of research, up to date most of the studies have focused
      on finding a subset of features that maximizes accuracy. However, maximizing
      accuracy does not guarantee reliable interpretation as similar accuracies can be
      obtained from distinct sets of features. In the current paper we propose a new
      approach for selecting features: SCoRS (survival count on random subsamples)
      based on a recently proposed Stability Selection theory. SCoRS relies on the idea
      of choosing relevant features that are stable under data perturbation. Data are
      perturbed by iteratively sub-sampling both features (subspaces) and examples. We
      demonstrate the potential of the proposed method in a clinical application to
      classify depressed patients versus healthy individuals based on functional
      magnetic resonance imaging data acquired during visualization of happy faces. 

PMID- 24043374
TI  - Higher body weight patients on clopidogrel maintenance therapy have lower active
      metabolite concentrations, lower levels of platelet inhibition, and higher rates
      of poor responders than low body weight patients.
AB  - Body weight is a predictor of clopidogrel response. However, no prospective
      studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on
      body weight. We compared PD and PK effects of clopidogrel 75 mg in low body
      weight (LBW, <60 kg) and higher body weight (HBW, >=60 kg) patients with stable
      coronary artery disease. LBW (n = 34, 56.4 +/- 3.7 kg) and HBW (n = 38, 84.7 +/-
      14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10-14 days. The
      area under the concentration-time curve of active metabolite (Clop-AM) calculated
      through the last quantifiable concentration up to 4 h postdose, AUC(0-tlast), was
      calculated by noncompartmental methods. Light transmission aggregometry (LTA)
      (maximum platelet aggregation and inhibition of platelet aggregation to 20 MUM
      adenosine diphosphate (ADP), and residual platelet aggregation to 5 MUM ADP),
      VerifyNow((r)) P2Y12 reaction units (PRU), and vasodilator-associated stimulated
      phosphoprotein phosphorylation platelet reactivity index (VASP-PRI) were
      performed. Mean AUC(0-tlast) was lower in HBW than LBW patients: 12.8 versus 17.9
      ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p <=
      0.01), PRU (207 +/- 68 vs. 152 +/- 57, p < 0.001), and VASP-PRI (56 +/- 18 vs. 39
      +/- 17, p < 0.001). More HBW patients exhibited high on-treatment platelet
      reactivity (HPR) using PRU (35 vs. 9%) and VASP-PRI (65 vs. 27%). Body weight
      correlated with PRU and VASP-PRI (both p < 0.001), and inversely with log
      transformed AUC(0-tlast) (p < 0.001). In conclusion, HBW patients had lower
      levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW
      subjects, contributing to their suboptimal response to clopidogrel.

PMID- 24043375
TI  - Comparative efficacy of in vitro and in vivo metabolized aspirin in the DeBakey
      ventricular assist device.
AB  - Ventricular assist devices (VADs) are implanted in patients with end-stage heart
      failure to provide both short- and long-term hemodynamic support. Unfortunately,
      bleeding and thromboembolic complications due to the severely disturbed, dynamic
      flow conditions generated within these devices require complex, long-term
      antiplatelet and anticoagulant therapy. While several studies have examined the
      effectiveness of one such agent, aspirin, under flow conditions, data comparing
      the efficacy of in vitro and in vivo metabolized aspirin is lacking. Two sets of
      studies were conducted in vitro with purified human platelets circulating for 30
      min in a flow loop containing the DeBakey VAD (MicroMed Cardiovascular, Houston,
      TX, USA): (a) 20 MUM aspirin was added exogenously in vitro to platelets isolated
      from aspirin-free subjects, and (b) platelets were obtained from donors 2 h (n =
      14) and 20 h (n = 13) after ingestion of 1,000 mg aspirin. Near real-time
      platelet activation state (PAS) was measured with a modified prothrombinase-based
      assay. Platelets exposed to aspirin in vitro and in vivo (metabolized) showed
      28.2 and 25.3 % reduction in platelet activation rate, respectively, compared to
      untreated controls. Our results demonstrate that in vitro treatment with
      antiplatelet drugs such as aspirin is as effective as in vivo metabolized aspirin
      in testing the effect of reducing shear-induced platelet activation in the VAD.
      Using the PAS assay provides a practical in vitro alternative to in vivo testing
      of antiplatelet efficacy, as well as for testing the thrombogenic performance of
      devices during their research and development. 

PMID- 24043376
TI  - Enantioseparation of flinderoles and borreverines by HPLC on Chirobiotic V and V2
      stationary phases and by CE using cyclodextrin selectors.
AB  - Racemic mixtures of the promising anti-malarial bisindole alkoids, flinderole A
      C, desmethyl flinderole C, borreverine and isoborreverine, are baseline-separated
      for the first time by HPLC using vancomycin-based stationary phases and partially
      separated by capillary electrophoresis (CE) using cyclodextrin selectors. The
      HPLC results compare the performance of Chirobiotic V and V2 in the polar organic
      and reversed phase modes and their complementary selectivity is discussed. The
      performance of the cyclodextrin selectors in CE, while less effective, are
      discussed in terms of their selectivity in normal and reversed polarity modes. 

PMID- 24043377
TI  - Selection of 2'F-modified RNA aptamers against prostate-specific antigen and
      their evaluation for diagnostic and therapeutic applications.
AB  - Currently, prostate-specific antigen (PSA) is considered to be the most sensitive
      marker available for prostate cancer detection and for monitoring of disease
      progression. In addition to its importance as a tumor marker, PSA has a role in
      the biological activity of cancer growth and proliferation. Therefore, the
      inhibition or activation of its biological activity may be used in prostate
      cancer therapy. Here, we describe the isolation and characterization of new 2'F
      modified RNA aptamers directed against PSA. Binding studies demonstrate the
      ability of these new aptamers to specifically recognize their target with
      dissociation constants in the nanomolar range. In order to demonstrate the
      functionality of the selected aptamers, an apta-PCR approach was used for the
      quantitative detection of PSA, achieving a limit of detection of 11 nM.
      Furthermore, the potential use of the selected aptamers in therapeutics was
      demonstrated with the 2'F-modified aptamers being highly stable in human serum
      and having the ability to moderate the activity of PSA, which will be explored
      for the treatment of prostate cancer.

PMID- 24043378
TI  - The analytical challenges of anti-doping analysis.

PMID- 24043379
TI  - The catheter-over-needle assembly offers greater stability and less leakage
      compared with the traditional counterpart in continuous interscalene nerve
      blocks: a randomized patient-blinded study.

PMID- 24043380
TI  - Tract-based evaluation of white matter damage in individuals with early-treated
      phenylketonuria.
AB  - Previous research has documented white matter abnormalities in the brains of
      individuals with early-treated phenylketonuria (ETPKU). The majority of these
      past studies have relied on a region-based approach which focused on a limited
      number of spatially-defined regions within the brain. In the present study, we
      used diffusion tensor imaging (DTI) in conjunction with tract-based spatial
      statistics (TBSS) to perform an extensive examination of white matter tracts in
      the brains of ten individuals with ETPKU (mean age = 23.2 years) and 12 healthy
      non-PKU individuals (mean age = 23.5 years). Consistent with past research, we
      found that mean diffusivity (MD) was significantly restricted in the ETPKU group,
      and fractional anisotropy (FA) was comparable between the ETPKU and non-PKU
      groups. Moreover, we found restricted axial diffusivity (AD) and radial
      diffusivity (RD) in our ETPKU in numerous white matter tracts, suggesting
      widespread white matter compromise in ETPKU. In addition, this white matter
      pathology was more evident in older ETPKU participants with higher blood
      phenylalanine (phe) levels as compared to younger participants with lower phe
      levels. 

PMID- 24043381
TI  - Considering consent: a structural equation modelling analysis of factors
      influencing decisional quality when accepting newborn screening.
AB  - INTRODUCTION: Newborn bloodspot screening (NBS) programs generate an ethical
      tension between promoting the uptake of effective public health measures and
      facilitating informed consent from individuals. AIM: To explore the factors that
      affect parental perceptions of decision quality when accepting NBS METHODS:
      Survey of parents with children screened in 2008 (n = 154, 32% response rate).
      Questions were based on previous research and existing measures. The primary
      outcome was decision quality. Predictors were latent constructs of Attitudes to
      medicine, Perceived knowledge, Attitudes to screening, and Perceived choice.
      Responses were analysed using structural equation modelling. RESULTS: Increases
      in perceived choice and positive attitudes towards screening improved decision
      quality. Perceived knowledge had a significant and positive relationship with
      attitudes to screening (0.375, p < 0.01) as did perceived choice on perceived
      knowledge (0.806, p < 0.01). Attitudes to screening were also significantly
      influenced by attitudes to medicine, although less so than the effect of
      perceived knowledge. The model had good fit on all indices (chi(2) = 61.396, df =
      48, p = 0.093; CFI = 0.979; RMSEA = 0.043). CONCLUSIONS: Our results implicate
      the presentation of screening as a key determinant of decision quality both in
      terms of the immediate information regarding the potential benefits and risks,
      but also the way in which consent processes are managed. If we want to better
      understand parent decision-making we need to go beyond analyses of information
      content, or parental recall of this, but consider the context in which screening
      is provided.

PMID- 24043382
TI  - Unknown pathomechanisms of renal impairment in PKU.

PMID- 24043383
TI  - Reproductive implications of psychological distress for couples undergoing IVF.
AB  - OBJECTIVE: To study implications of psychological distress on in vitro
      fertilization (IVF) outcome of an infertile couple. METHODS: Prospective study in
      an academic infertility practice setting. Couples undergoing embryo transfer (ET)
      following IVF were offered participation. Female patient (n = 89) and partner (n
      = 77) completed questionnaires reflecting dysphoria (POMS) and pessimism (LOT)
      after undergoing ET. Relationship between dysphoria and pessimism and
      implications of individual and couple's psychological distress on IVF cycle
      parameters and outcomes were assessed using multivariable analyses. RESULTS:
      Statistically significant correlations between dysphoria and pessimism were
      observed within the individual and between partners, (p < 0.01). Higher couple
      pessimism correlated with longer duration of controlled ovarian hyperstimulation
      (COH, p = 0.02); higher partner psychological distress related to lower
      fertilization rate (FR, p = 0.03). On adjusted analyses, partner's depression
      score was an independent predictor of reduced likelihood of clinical pregnancy (p
      = 0.03). CONCLUSIONS: Our data validate the concept of a "stressed couple".
      Adverse implications of a couple's psychological distress for gamete biology
      (longer duration of COH and lower FR with increasing distress) are suggested.
      Partner's depressive scores negatively correlated with IVF success. These
      findings suggest the importance of including partner's evaluation in studies that
      focus on effects of psychological stress on IVF outcome; future studies should
      examine whether interventions aimed at reducing psychological stress for the
      infertile couple may improve IVF cycle success.

PMID- 24043385
TI  - Compressive source separation: theory and methods for hyperspectral imaging.
AB  - We propose and analyze a new model for hyperspectral images (HSIs) based on the
      assumption that the whole signal is composed of a linear combination of few
      sources, each of which has a specific spectral signature, and that the spatial
      abundance maps of these sources are themselves piecewise smooth and therefore
      efficiently encoded via typical sparse models. We derive new sampling schemes
      exploiting this assumption and give theoretical lower bounds on the number of
      measurements required to reconstruct HSI data and recover their source model
      parameters. This allows us to segment HSIs into their source abundance maps
      directly from compressed measurements. We also propose efficient optimization
      algorithms and perform extensive experimentation on synthetic and real datasets,
      which reveals that our approach can be used to encode HSI with far less
      measurements and computational effort than traditional compressive sensing
      methods. 

PMID- 24043384
TI  - Human chorionic gonadotropin levels are equally predictive for pregnancy outcome
      after fresh and vitrified-warmed blastocyst transfer.
AB  - PURPOSE: The aim of the present study was to evaluate if the live birth
      predictive values of beta-hCG levels differ in fresh and vitrified-warmed
      blastocyst transfer cycles. METHODS: In the retrospectively designed study, 775
      cycles with positive beta-hCG values 13 days after fresh blastocyst transfer
      (fresh ET; n = 568) or vitrified-warmed blastocyst transfer (FET; n = 207) were
      selected for analysis. Average beta-hCG levels stratified according to pregnancy
      outcome (biochemical pregnancy, spontaneous abortion, ectopic pregnancy, and
      singleton or twin birth) were compared between fresh ET and FET cycles. To
      determine the optimal sensitivity and specificity of beta-hCG levels for live
      birth prediction, a ROC curve was constructed. Fisher's exact test was used to
      compare the positive predictive values (PPV). RESULTS: Average beta-hCG levels
      stratified according to pregnancy outcome were not statistically different
      between fresh ET and FET cycles. In fresh ET and in FET group, the beta-hCG
      levels were significantly higher in pregnancies resulting in live birth compared
      to non-viable pregnancies (1,035 vs. 462 IU/L, p < 0.001 and 968 vs. 411 IU/L, p
      < 0.001). Optimal cut-off level for live birth prediction was 495 IU/L
      (sensitivity 83.0 %, specificity 71.8 %) after ET and 527 IU/L (sensitivity 80.0
      % and specificity 76.6 %) after FET. The PPV for live birth rate in the groups
      after ET and FET were 90.6 % and 84.9 % respectively, without statistically
      significant difference (p > 0.05). CONCLUSION: Beta-hCG levels after fresh and
      vitrified-warmed blastocyst transfer are equally predictive for pregnancy
      outcome. Clinicians can be encouraged to interpret beta-hCG results in the same
      manner.

PMID- 24043386
TI  - Object detection via structural feature selection and shape model.
AB  - In this paper, we propose an approach for object detection via structural feature
      selection and part-based shape model. It automatically learns a shape model from
      cluttered training images without need to explicitly use bounding boxes on
      objects. Our approach first builds a class-specific codebook of local contour
      features, and then generates structural feature descriptors by combining context
      shape information. These descriptors are robust to both within-class variations
      and scale changes. Through exploring pairwise image matching using fast earth
      mover's distance, feature weights can be iteratively updated. Those
      discriminative foreground features are assigned high weights and then selected to
      build a part-based shape model. Finally, object detection is performed by
      matching each testing image with this model. Experiments show that the proposed
      method is very effective. It has achieved comparable performance to the state-of
      the-art shape-based detection methods, but requires much less training
      information.

PMID- 24043387
TI  - Infrared patch-image model for small target detection in a single image.
AB  - The robust detection of small targets is one of the key techniques in infrared
      search and tracking applications. A novel small target detection method in a
      single infrared image is proposed in this paper. Initially, the traditional
      infrared image model is generalized to a new infrared patch-image model using
      local patch construction. Then, because of the non-local self-correlation
      property of the infrared background image, based on the new model small target
      detection is formulated as an optimization problem of recovering low-rank and
      sparse matrices, which is effectively solved using stable principle component
      pursuit. Finally, a simple adaptive segmentation method is used to segment the
      target image and the segmentation result can be refined by post-processing.
      Extensive synthetic and real data experiments show that under different clutter
      backgrounds the proposed method not only works more stably for different target
      sizes and signal-to-clutter ratio values, but also has better detection
      performance compared with conventional baseline methods.

PMID- 24043388
TI  - Pairwise prediction-error expansion for efficient reversible data hiding.
AB  - In prediction-error expansion (PEE) based reversible data hiding, better
      exploiting image redundancy usually leads to a superior performance. However, the
      correlations among prediction-errors are not considered and utilized in current
      PEE based methods. Specifically, in PEE, the prediction-errors are modified
      individually in data embedding. In this paper, to better exploit these
      correlations, instead of utilizing prediction-errors individually, we propose to
      consider every two adjacent prediction-errors jointly to generate a sequence
      consisting of prediction-error pairs. Then, based on the sequence and the
      resulting 2D prediction-error histogram, a more efficient embedding strategy,
      namely, pairwise PEE, can be designed to achieve an improved performance. The
      superiority of our method is verified through extensive experiments.

PMID- 24043389
TI  - Multiresolution based Gaussian mixture model for background suppression.
AB  - This paper aims toward improving background suppression from video frames by
      incorporating multiresolution features in Gaussian mixture model (GMM). GMM has
      proven its place for background modeling due to its better applicability and
      robustness compared with other popular methods in literature. However, GMM fails
      in a number of situations such as noisy and non-stationary background, slow
      foregrounds, and illumination variation. Extensions to GMM have also been
      proposed to increase accuracy in expense of increased complexity, decrease in
      execution speed, and reduced applicability. In view of the above, this paper aims
      to provide a methodology to assimilate useful multiresolution features with GMM
      that considerably improves the performance. The contributions of this paper are:
      1) a novel framework to incorporate wavelet subbands in GMM to improve its
      performance; 2) an approach to incorporate variable number of clusters in the
      aforesaid framework; and 3) a generic platform to use any multiresolution
      decomposition based GMM for background suppression. Extensive experimentations on
      several video sequences are performed to verify the improvement in accuracy
      compared with conventional GMM as well as a number of state-of-the-arts
      approaches. Along with qualitative and quantitative analysis, justification on
      the use of multiresolution is provided for clarification.

PMID- 24043390
TI  - The richer representation the better registration.
AB  - In this paper, the registration problem is formulated as a point to model
      distance minimization. Unlike most of the existing works, which are based on
      minimizing a point-wise correspondence term, this formulation avoids the
      correspondence search that is time-consuming. In the first stage, the target set
      is described through an implicit function by employing a linear least squares
      fitting. This function can be either an implicit polynomial or an implicit B
      spline from a coarse to fine representation. In the second stage, we show how the
      obtained implicit representation is used as an interface to convert point-to
      point registration into point-to-implicit problem. Furthermore, we show that this
      registration distance is smooth and can be minimized through the Levengberg
      Marquardt algorithm. All the formulations presented for both stages are compact
      and easy to implement. In addition, we show that our registration method can be
      handled using any implicit representation though some are coarse and others
      provide finer representations; hence, a tradeoff between speed and accuracy can
      be set by employing the right implicit function. Experimental results and
      comparisons in 2D and 3D show the robustness and the speed of convergence of the
      proposed approach.

PMID- 24043391
TI  - Reconstruction based finger-knuckle-print verification with score level adaptive
      binary fusion.
AB  - Recently, a new biometrics identifier, namely finger knuckle print (FKP), has
      been proposed for personal authentication with very interesting results. One of
      the advantages of FKP verification lies in its user friendliness in data
      collection. However, the user flexibility in positioning fingers also leads to a
      certain degree of pose variations in the collected query FKP images. The widely
      used Gabor filtering based competitive coding scheme is sensitive to such
      variations, resulting in many false rejections. We propose to alleviate this
      problem by reconstructing the query sample with a dictionary learned from the
      template samples in the gallery set. The reconstructed FKP image can reduce much
      the enlarged matching distance caused by finger pose variations; however, both
      the intra-class and inter-class distances will be reduced. We then propose a
      score level adaptive binary fusion rule to adaptively fuse the matching distances
      before and after reconstruction, aiming to reduce the false rejections without
      increasing much the false acceptances. Experimental results on the benchmark
      PolyU FKP database show that the proposed method significantly improves the FKP
      verification accuracy.

PMID- 24043392
TI  - Common recognition principles across diverse sequence and structural families of
      sialic acid binding proteins.
AB  - Sialic acids form a large family of 9-carbon monosaccharides and are integral
      components of glycoconjugates. They are known to bind to a wide range of
      receptors belonging to diverse sequence families and fold classes and are key
      mediators in a plethora of cellular processes. Thus, it is of great interest to
      understand the features that give rise to such a recognition capability.
      Structural analyses using a non-redundant data set of known sialic acid binding
      proteins was carried out, which included exhaustive binding site comparisons and
      site alignments using in-house algorithms, followed by clustering and tree
      computation, which has led to derivation of sialic acid recognition principles.
      Although the proteins in the data set belong to several sequence and structure
      families, their binding sites could be grouped into only six types. Structural
      comparison of the binding sites indicates that all sites contain one or more
      different combinations of key structural features over a common scaffold. The six
      binding site types thus serve as structural motifs for recognizing sialic acid.
      Scanning the motifs against a non-redundant set of binding sites from PDB
      indicated the motifs to be specific for sialic acid recognition. Knowledge of
      determinants obtained from this study will be useful for detecting function in
      unknown proteins. As an example analysis, a genome-wide scan for the motifs in
      structures of Mycobacterium tuberculosis proteome identified 17 hits that contain
      combinations of the features, suggesting a possible function of sialic acid
      binding by these proteins. 

PMID- 24043394
TI  - Clinical comparison of four types of skin incisions for skin-sparing mastectomy
      and immediate breast reconstruction.
AB  - PURPOSE: Skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR)
      has become popular as an effective procedure for patients with early breast
      cancer. We herein report an overview of the four types of skin incisions used for
      SSM. METHODS: The records of 111 consecutive breast cancer patients, who received
      SSM and IBR from 2003 to 2012, were reviewed retrospectively. Four types of skin
      incisions were used. Type A was the so-called tennis racquet incision, type B was
      a periareolar incision and mid-axillary incision, type C was the so-called areola
      sparing with mid-axillary incision and type D was a small transverse elliptical
      incision and transverse axillary incision. RESULTS: Twenty-six type A, 59 type B,
      20 type C and six type D incisions were made. The average blood loss and average
      length of the operation during SSM were not significantly different between the
      four approaches. The average areolar diameter was 35 mm for type A, B and D
      incisions, and 45 mm for type C. There was a need for postoperative nipple
      areolar complex plasty (NAC-P) in 75 % of the cases following type A, B and D
      incisions, and 35 % of the cases treated using type C incisions. CONCLUSION: The
      type C incision is superior with regard to the cost and cosmetic outcomes,
      because fewer of these patients request postoperative NAC-P.

PMID- 24043395
TI  - Compliance with physical exercise: using a multidisciplinary approach within a
      dose-dependent exercise study of moderately overweight men.
AB  - AIMS: Sixty-one healthy, sedentary, moderately overweight young men participated
      in a randomised controlled trial to examine the effects of two different doses of
      endurance exercise on health behaviour and exercise compliance. METHODS:
      Participants were randomised to a sedentary control group, a moderate (MOD; 300
      kcal/day) or a high-dose (HIGH; 600 kcal/day) endurance exercise group for 12
      weeks. A sub-set of the subjects were interviewed using pre-determined,
      qualitative questions to elucidate physical activity and health behaviour. In
      combination with the Theory of Planned Behaviour (TPB), a post hoc thematic
      analysis was conducted to connect qualitative and quantitative data in a joint
      analysis. RESULTS: Of the subjects interviewed, exercise compliance expressed as
      95% CI was [96.8; 103%] in the MOD group and [82.9; 99.6%] in the HIGH group. The
      different doses of daily exercise equally improved various metabolic health
      parameters. The MOD group was untroubled by the exercise load and had a positive
      attitude towards exercise. The HIGH group expressed increased fatigue, less
      positivity and perceived exercise as time-consuming. The MOD group described
      themselves as more energetic, and thereby may have increased physical activity
      levels in areas of their everyday lives that were not related to the
      intervention. CONCLUSIONS: A multidisciplinary approach provided explanations for
      similar effects of two different doses of exercise. This could not have been
      determined via either qualitative or quantitative methodology alone. The
      preconditions of the TBP were fulfilled, and it represents a methodological model
      to explain the high degree of compliance and motivation to exercise.

PMID- 24043396
TI  - Normative data of BMI and physical fitness in a Norwegian sample of early
      adolescents.
AB  - AIM: The purpose of the present study was to 1) provide normative data
      quantifying the physical fitness level and body mass index of 13-15-year-old
      Norwegian adolescents using a multi-component fitness assessment, and 2) compare
      the physical fitness of Norwegian teenagers with available European and
      International fitness data. METHODS: 1059 adolescents (529 males, 530 females)
      from 12 public schools in Kristians and were invited to testing at age 13, 14,
      and 15 years (Grades 8-10). Test participation was 75%-80%. The participants
      performed objectively anthropometrical measures (height and weight) and six field
      based physical fitness tests. RESULTS AND CONCLUSIONS: As expected, sex
      differences in physical fitness expanded from age 13 to 15. Strength and power
      increased more in males than females. Aerobic capacity increased slightly in
      males while remaining stable or tending to decline in females. Balance and gross
      motor coordination improved identically in males and females from age 13 to 15.
      Compared to European and International reference data, the sample performed
      superior in endurance and balance, slightly above median in lower-body strength,
      but inferior in flexibility.

PMID- 24043397
TI  - Molecular and functional characterization of the HbSRPP promoter in response to
      hormones and abiotic stresses.
AB  - Small rubber particle protein (SRPP) is a major component of Hevea brasiliensis
      latex, and obviously participates in the biosynthesis of natural rubber. However,
      little information is available about regulation of SRPP gene expression. In this
      study, the promoter region of HbSRPP was isolated and characterized. Its sequence
      included regulatory elements predicted to be responsive to hormones and other
      environmental cues. Promoter deletion analysis revealed that 219 nucleotides (nt)
      upstream of the transcription start site were sufficient for expression. The
      region from -1,055 to -219 nt positively regulated expression induced by methyl
      jasmonate (MeJA), abscisic acid (ABA), and wounding; the region from -734 to -528
      nt positively regulated expression induced by gibberellic acid (GA); the region
      from -734 to -219 nt positively regulated expression induced by heat; the region
      from -1,055 to -4 negatively regulated expression induced by cold; the region
      from -219 to -4 nt was associated with negative regulation of expression induced
      by ABA and wounding; the region from -528 to -4 nt negatively regulated
      expression induced by GA. These results suggest the activity of the HbSRPP
      promoter is regulated by MeJA, ABA, GA, cold, heat, and wounding. 

PMID- 24043398
TI  - Wide-Range Filter-Based Sinusoidal Wave Synthesizer for Electrochemical Impedance
      Spectroscopy Measurements.
AB  - A filter-based wide-range programmable sinusoidal wave synthesizer for
      electrochemical impedance spectroscopy measurement is proposed. The adopted
      filter is implemented with switched-capacitor circuits, so its corner frequency
      is accurate and adjustable by changing its switching frequency. The proposed sine
      wave synthesizer is implemented by using a 0.35 MUm 2P4M 3.3 V mixed-signal
      polycide process. According to the measured results, the output frequency of the
      proposed synthesizer is 40 mHz-40 kHz . The measured total harmonic distortion is
      0.073% at 10 Hz and 0.075% at 10 kHz, both of which are better than that of a
      typical function generator.

PMID- 24043400
TI  - Duodenal gastrointestinal stromal tumor presenting as massive gastrointestinal
      bleed.

PMID- 24043399
TI  - Complications of ERCP.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is performed commonly for
      therapy. Its role in pancreaticobiliary diagnostic imaging has significantly
      decreased over time. Despite advances in our knowledge of the risk factors,
      complications, (especially post-ERCP pancreatitis), remain a significant problem.
      This review highlights the risk factors as related to the patient, procedure and
      the endoscopist, and the possible means to prevent complications. The best way to
      avoid any complication is "to avoid any procedure where the indication is not
      strong" and especially to refrain from doing diagnostic ERCP when alternate
      noninvasive imaging such as magnetic resonance cholangiopancreatography is
      available. 

PMID- 24043401
TI  - Benign solitary cecal ulcer.

PMID- 24043402
TI  - Source analysis of event-related potentials during pitch discrimination and pitch
      memory tasks.
AB  - Our previous studies using fMRI have demonstrated that activations in human
      auditory cortex (AC) are strongly dependent on the characteristics of the task.
      The present study tested whether source estimation of scalp-recorded event
      related potentials (ERPs) can be used to investigate task-dependent AC
      activations. Subjects were presented with frequency-varying two-part tones during
      pitch discrimination, pitch n-back memory, and visual tasks identical to our
      previous fMRI study (Rinne et al., J Neurosci 29:13338-13343, 2009). ERPs and
      their minimum-norm source estimates in AC were strongly modulated by task at 200
      700 ms from tone onset. As in the fMRI study, the pitch discrimination and pitch
      memory tasks were associated with distinct AC activation patterns. In the pitch
      discrimination task, increased activity in the anterior AC was detected
      relatively late at 300-700 ms from tone onset. Therefore, this activity was
      probably not associated with enhanced pitch processing but rather with the actual
      discrimination process (comparison between the two parts of tone). Increased
      activity in more posterior areas associated with the pitch memory task, in turn,
      occurred at 200-700 ms suggesting that this activity was related to operations on
      pitch categories after pitch analysis was completed. Finally, decreased activity
      associated with the pitch memory task occurred at 150-300 ms consistent with the
      notion that, in the demanding pitch memory task, spectrotemporal analysis is
      actively halted as soon as category information has been obtained. These results
      demonstrate that ERP source analysis can be used to complement fMRI to
      investigate task-dependent activations of human AC. 

PMID- 24043403
TI  - Current initiatives to improve prudent antibiotic use amongst school-aged
      children.
AB  - High rates of antimicrobial prescribing for children, combined with widespread
      misunderstanding among the general public about the appropriate use of
      antibiotics, are major causes for concern. European Antibiotic Awareness Day
      (EAAD) is an annual event that aims to raise awareness of how to use antibiotics
      in a responsible way that will help keep them effective for the future. As part
      of EAAD 2013, this article provides an overview of some initiatives aimed at
      limiting the extent of inappropriate antibiotic use in children. 

PMID- 24043404
TI  - Regulation of acrAB expression by cellular metabolites in Escherichia coli.
AB  - OBJECTIVES: Multidrug efflux pumps mediate resistance to antibiotics and other
      toxic compounds. We studied the role of AcrAB-TolC, the main efflux pump in
      Escherichia coli, in regulating gene expression. METHODS: Deletion mutants, an
      acrABp-lacZ fusion and reverse transcription-real-time quantitative PCR
      experiments were used to study the role of AcrAB-TolC and metabolism in
      regulating gene expression of the acrAB operon and its transcriptional
      regulators. RESULTS: Deletion of the acrB gene increased the expression of the
      acrAB operon. A similar induction of acrAB was found when acrA or tolC was
      deleted, and when the pump function was inhibited using phenylalanine-arginine
      beta-naphthylamide. The induction of acrAB in the DeltaacrB strain was totally
      (AcrR or SoxS) or partially (SoxR or MarA) prevented when the genes for these
      acrAB regulators were also deleted. The expression of soxS and marA, but not of
      acrR, was increased in the DeltaacrB strain, which also showed altered expression
      of many other genes related to different cellular processes, including motility.
      Deletion of the metabolic genes entA and entE (enterobactin biosysnthesis), glpX
      (gluconeogenesis), cysH (cysteine biosynthesis) and purA (purine biosynthesis)
      also prevented activation of the acrAB promoter in the DeltaacrB strain. Addition
      of the enterobactin biosynthesis intermediate metabolite 2,3-dihydroxybenzoate
      induced the expression of acrAB. CONCLUSIONS: These results together suggest a
      model in which the AcrAB-TolC pump effluxes cellular metabolites that are toxic
      and/or have a signalling role. If the pump is inactivated or inhibited, these
      metabolites would accumulate, inactivating AcrR and/or up-regulating soxS and
      marA expression, ultimately triggering the up-regulation of acrAB expression to
      restore homeostasis.

PMID- 24043405
TI  - Who's asking the important questions? Sexual topics discussed among young
      pregnant couples.
AB  - The aim was to examine gender differences in sexual risk communication among
      young couples and factors influencing communication. Sample consisted of 296
      young pregnant couples. We assessed individual, interpersonal, and community
      factors on sexual risk communication. The Actor-Partner Independence Model was
      used to assess actor and partner effects on sexual risk communication. For actor
      effects, being female, older, not being Hispanic, and higher condom use self
      efficacy was associated with sexual risk communication. The significant partner
      effect was avoidant romantic attachment. Gender interactions were significant for
      high risk behaviors and family functioning. High risk behaviors and family
      functioning were associated with sexual risk communication for females but not
      for males. The study emphasizes the need to promote sexual risk communication
      among young high risk couples, particularly for males. Family support could serve
      as a catalyst for sexual risk communication and other sexual protective behaviors
      among young couples. 

PMID- 24043406
TI  - HIV testing in an ethnically diverse sample of American university students:
      associations with violence/abuse and covariates.
AB  - Associations linking HIV infection to violence and abuse are well documented;
      however, little is known about how violence/abuse is related to HIV testing
      behavior, particularly among undergraduate university students, who test at lower
      rates compared to non-student peers in the United States. We assessed history of
      HIV testing in an ethnically diverse sample of undergraduates in California (n =
      1,210); and examined potential associations between testing and various forms of
      violence/abuse, while controlling for covariates. Whereas 73.4% of students were
      sexually active in the past year, only 26.3% had ever tested for HIV. At the
      bivariate level, testing was associated with experiencing verbal abuse and sexual
      violence/coercion, and perpetrating verbal abuse. Experiencing verbal abuse
      remained significant in multivariate analysis. We discuss findings in a syndemics
      framework, considered in combination with social psychology-based health behavior
      theories. Enhanced HIV testing scale-up initiatives for undergraduates are needed
      and should consider integration with violence prevention programs.

PMID- 24043408
TI  - Automated ingestion detection for a health monitoring system.
AB  - Obesity is a global epidemic that imposes a financial burden and increased risk
      for a myriad of chronic diseases. Presented here is an overview of a prototype
      automated ingestion detection (AID) process implemented in a health monitoring
      system (HMS). The automated detection of ingestion supports personal record
      keeping which is essential during obesity management. Personal record keeping
      allows the care provider to monitor the therapeutic progress of a patient. The
      AID-HMS determines the levels of ingestion activity from sounds captured by an
      external throat microphone. Features are extracted from the sound recording and
      presented to machine learning classifiers, where a simple voting procedure is
      employed to determine instances of ingestion. Using a dataset acquired from seven
      individuals consisting of consumption of liquid and solid, speech, and
      miscellaneous sounds, > 94% of ingestion sounds are correctly identified with
      false positive rates around 9% based on 10-fold cross validation. The detected
      levels of ingestion activity are transmitted and stored on a remote web server,
      where information is displayed through a web application operating in a web
      browser. This information allows remote users (health provider) determine meal
      lengths and levels of ingestion activity during the meal. The AID-HMS also
      provides a basis for automated reinforcement for the patient.

PMID- 24043409
TI  - Augmenting breath regulation using a mobile driven virtual reality therapy
      framework.
AB  - This paper presents a conceptual framework of a virtual reality therapy to assist
      individuals, especially lung cancer patients or those with breathing disorders to
      regulate their breath through real-time analysis of respiration movements using a
      smartphone. Virtual reality technology is an attractive means for medical
      simulations and treatment, particularly for patients with cancer. The theories,
      methodologies and approaches, and real-world dynamic contents for all the
      components of this virtual reality therapy (VRT) via a conceptual framework using
      the smartphone will be discussed. The architecture and technical aspects of the
      offshore platform of the virtual environment will also be presented. 

PMID- 24043407
TI  - Recent advances in sleep-wake cycle and biological rhythms in bipolar disorder.
AB  - The cyclical nature of periodic switches in energy, motor activation and sleep
      wake cycles in bipolar disorder suggests a strong underlying relationship with
      disturbances in chronobiology. Current research is refining our understanding of
      the various patterns of sleep-wake and biological rhythms alterations at early
      and later stages of this illness, as well as across its depressive/fatigue,
      manic/hypomanic and euthymic phases. This research focuses on early detection and
      subsequent monitoring to predict and better manage recurrent episodes. Sleep-wake
      cycle and biological rhythms disturbances are also well known to affect other key
      aspects of physical health (notably metabolic functions), cognitive performance
      and elevated risks for suicide. Increasing evidence now supports the integration
      of behavioural or pharmacological therapeutic strategies that target the sleep
      wake and circadian systems in the ongoing treatment of various phases of bipolar
      disorder. 

PMID- 24043410
TI  - A joint FED watermarking system using spatial fusion for verifying the security
      issues of teleradiology.
AB  - Teleradiology allows transmission of medical images for clinical data
      interpretation to provide improved e-health care access, delivery, and standards.
      The remote transmission raises various ethical and legal issues like image
      retention, fraud, privacy, malpractice liability, etc. A joint FED watermarking
      system means a joint fingerprint/encryption/dual watermarking system is proposed
      for addressing these issues. The system combines a region based substitution dual
      watermarking algorithm using spatial fusion, stream cipher algorithm using
      symmetric key, and fingerprint verification algorithm using invariants. This
      paper aims to give access to the outcomes of medical images with confidentiality,
      availability, integrity, and its origin. The watermarking, encryption, and
      fingerprint enrollment are conducted jointly in protection stage such that the
      extraction, decryption, and verification can be applied independently. The dual
      watermarking system, introducing two different embedding schemes, one used for
      patient data and other for fingerprint features, reduces the difficulty in
      maintenance of multiple documents like authentication data, personnel and
      diagnosis data, and medical images. The spatial fusion algorithm, which
      determines the region of embedding using threshold from the image to embed the
      encrypted patient data, follows the exact rules of fusion resulting in better
      quality than other fusion techniques. The four step stream cipher algorithm using
      symmetric key for encrypting the patient data with fingerprint verification
      system using algebraic invariants improves the robustness of the medical
      information. The experiment result of proposed scheme is evaluated for security
      and quality analysis in DICOM medical images resulted well in terms of attacks,
      quality index, and imperceptibility. 

PMID- 24043411
TI  - Local object patterns for the representation and classification of colon tissue
      images.
AB  - This paper presents a new approach for the effective representation and
      classification of images of histopathological colon tissues stained with
      hematoxylin and eosin. In this approach, we propose to decompose a tissue image
      into its histological components and introduce a set of new texture descriptors,
      which we call local object patterns, on these components to model their
      composition within a tissue. We define these descriptors using the idea of local
      binary patterns, which quantify a pixel by constructing a binary string based on
      relative intensities of its neighbors. However, as opposed to pixel-level local
      binary patterns, we define our local object pattern descriptors at the component
      level to quantify a component. To this end, we specify neighborhoods with
      different locality ranges and encode spatial arrangements of the components
      within the specified local neighborhoods by generating strings. We then extract
      our texture descriptors from these strings to characterize histological
      components and construct the bag-of-words representation of an image from the
      characterized components. Working on microscopic images of colon tissues, our
      experiments reveal that the use of these component-level texture descriptors
      results in higher classification accuracies than the previous textural
      approaches.

PMID- 24043412
TI  - A novel semisupervised algorithm for rare prescription side effect discovery.
AB  - Drugs are frequently prescribed to patients with the aim of improving each
      patient's medical state, but an unfortunate consequence of most prescription
      drugs is the occurrence of undesirable side effects. Side effects that occur in
      more than one in a thousand patients are likely to be signaled efficiently by
      current drug surveillance methods, however, these same methods may take decades
      before generating signals for rarer side effects, risking medical morbidity or
      mortality in patients prescribed the drug while the rare side effect is
      undiscovered. In this paper, we propose a novel computational metaanalysis
      framework for signaling rare side effects that integrates existing methods,
      knowledge from the web,metric learning, and semisupervised clustering. The novel
      framework was able to signal many known rare and serious side effects for the
      selection of drugs investigated, such as tendon rupture when prescribed
      Ciprofloxacin or Levofloxacin, renal failure with Naproxen and depression
      associated with Rimonabant. Furthermore, for the majority of the drugs
      investigated it generated signals for rare side effects at a more stringent
      signaling threshold than existing methods and shows the potential to become a
      fundamental part of post marketing surveillance to detect rare side effects.

PMID- 24043413
TI  - Bone temperature elevation by drilling friction and neurological outcome in the
      cervical spino-laminoplasty.
AB  - BACKGROUND: Drill-induced heat has been suspected as a cause of tissue injury,
      and there are ample experimental data to substantiate the implication. However,
      no clinical results have been presented with measurement of temperature in the
      vicinity of neural structures during the actual spinal procedures. METHODS: Using
      a thermocouple, temperature in the gutters drilled in the midline and the lateral
      margins of the lamina was monitored closely in 61 patients, who underwent the
      French-door style of cervical spino-laminoplasty. The drilling was performed
      intermittently for a duration of 5 or 10 seconds, using 3- or 5-mm diamond burrs
      with sufficient continuous cooling irrigation. The correlations between bone
      temperature elevation and postoperative sensorimotor symptoms were then analyzed.
      RESULTS: In the lateral gutters at the most cephalad level (typically C3), where
      the drilling was performed underneath an overlying bundle of muscle attached to
      C2's spinous process, the temperature rose significantly. This occurred even with
      5-second drilling sessions. The average peak temperature was 44  degrees C at
      this level. At all other sites, the temperature was maintained below 40  degrees
      C. In three patients, transient neurological deficit developed postoperatively,
      which did not correlate with the incidence of bone temperature elevation.
      CONCLUSIONS: Intermittent drilling with sufficient irrigation can prevent thermal
      neuronal damage generated by high-speed drills. Drilling with small diamond burrs
      in deep and narrow spaces covered by overlying muscles predisposes to inadequate
      irrigation and thermal elevation. Continuous, protracted drilling without
      frequent irrigation may result in excessive heat generation and nerve injury.

PMID- 24043414
TI  - Surgical strategy in grade II astrocytoma: a population-based analysis of
      survival and morbidity with a strategy of early resection as compared to watchful
      waiting.
AB  - BACKGROUND: We recently demonstrated a survival benefit of early resection in
      unselected diffuse low-grade gliomas (LGG). However, heterogeneity within the LGG
      entity warrants investigation in a homogenous subgroup. Astrocytoma represents
      the largest subgroup of LGG, and is characterized by diffuse growth and inferior
      prognosis. We aimed to study the effects of early resection compared to biopsy
      and watchful waiting in this subgroup. METHODS: Patient data was retrospectively
      reviewed in two neurosurgical departments with regional referral practice. In one
      hospital, initial diagnostic biopsies and watchful waiting was favored, while
      early resections guided with three-dimensional (3D) ultrasound were advocated in
      the other hospital. This created a natural experiment with patient management
      heavy influenced by residential address. In the hospitals' histopathology
      databases, all adult patients diagnosed with supratentorial LGG from 1998 through
      2009 were screened (n = 169) and underwent blinded histopathological review.
      Histopathological review concluded with 117 patients with grade II astrocytomas
      that were included in the present study. The primary end-point was overall
      survival assessed by a regional comparison. RESULTS: Early resections were
      performed in 51 (82 %) versus 12 (22 %) patients in the respective hospitals (p <
      0.001). The two patient populations were otherwise similar. Median survival was
      9.7 years (95 % CI 7.5-11.9) if treated in the hospital favoring early resections
      compared to 5.6 years (95 % CI 3.5-7.6) if treated at the hospital favoring
      biopsy and watchful waiting (p = 0.047). No difference in surgical-related
      neurological morbidity was seen (p = 0.843). CONCLUSIONS: Early 3D ultrasound
      guided resections improve survival, apparently without increased morbidity,
      compared to biopsy and watchful waiting in patients with diffuse World Health
      Organization (WHO) grade II astrocytomas.

PMID- 24043415
TI  - Analysis of the factors affecting graft infection after cranioplasty.
AB  - BACKGROUND: The predictors of graft infection after cranioplasty (GIC) following
      decompressive craniectomy are not well established. Knowledge of the risk factors
      for GIC will allow development of preventive measures designed to reduce
      infection rates. Therefore, the objective of this study was to identify risk
      factors for the development of GIC. METHODS: A total of 85 patients underwent
      reconstructive cranioplasty after decompressive craniectomy between January 2009
      and July 2011 and had a follow-up period of > 1 year; charts were reviewed
      retrospectively. Although autograft was used whenever possible, artificial bone
      was used for cranioplasty. GIC was defined as infection requiring removal of the
      bone graft. RESULTS: GIC occurred in six patients (7.05 %). GIC was not related
      to the indications for craniectomy, the interval of cranioplasty, graft material,
      or the size of the bone defect (p = 0.433, p = 0.206, p = 0.665, and p = 0.999,
      respectively). The GIC rate was significantly related to previous temporalis
      muscle resection, preoperative subgaleal fluid collection, operative times > 120
      min, and postoperative wound disruptions (p = 0.001, p < 0.001, p = 0.035, and p
      = 0.016, respectively). Multiple logistic regression showed that the presence of
      a subgaleal fluid collection before cranioplasty significantly increased the risk
      of GIC (OR: 38.53; 95 % CI: 2.77-535.6; p = 0.006). CONCLUSIONS: The results of
      this study suggest that long operative times (> 120 min), craniectomy with
      temporalis muscle resection, the presence of preoperative subgaleal fluid
      collection, and postoperative wound disruption may be risk factors for graft
      infection after cranioplasty. Surgical techniques should be developed to reduce
      operative time and to avoid temporalis muscle resection when possible. In
      addition, meticulous dural closure aimed at reducing the formation of subgaleal
      fluid collection is important for the prevention of graft infections after
      cranioplasty.

PMID- 24043416
TI  - Intracranial aneurysms in patients with internal carotid artery occlusion:
      management and outcome in 22 cases.
AB  - BACKGROUND: There is little information about clinical characteristics,
      management, and outcome of patients with intracranial aneurysms and internal
      carotid artery occlusion. We will describe clinical characteristics, treatment
      and outcome of patients with coexistent internal carotid artery occlusion and
      intracranial aneurysms. METHODS: We conducted a retrospective chart review of 22
      patients (eight males and 14 females) with coexistent internal carotid artery
      (ICA) occlusion and intracranial aneurysms. RESULTS: This series includes 14
      females and eight males with a mean age of 63 years (range, 49 to 80). These
      patients harbored a total of 35 aneurysms, which were located on the same side of
      the ICA occlusion in five cases, on the contralateral side in 20 cases, while in
      ten cases the aneurysm had a midline location (AcomA 9, Basilar tip 1). Treatment
      consisted of surgery for eight aneurysms and endovascular embolization for 13
      aneurysms. No invasive treatment was recommended for 14 aneurysms (eight patients
      with single aneurysm). No permanent perioperative or periprocedural complications
      occurred in the selected group of patients undergoing invasive treatment. At a
      mean follow-up of 57 months (range, 3-203), no patient had a subarachnoid
      hemorrhage and three patients had died of causes not related to the aneurysm.
      CONCLUSION: Surgical and endovascular treatment can be accomplished safely in
      selected patients with coexistent ICA occlusion and intracranial aneurysms.
      Conservative treatment is a valid alternative, especially in elderly patients or
      in patients with very small aneurysms, especially if not located along the
      collateral pathway.

PMID- 24043417
TI  - Performance of Nellore heifers, forage mass, and structural and nutritional
      characteristics of Brachiaria brizantha grass in integrated production systems.
AB  - Our objective was to evaluate production, nutritive value and carrying capacity
      of piata grass (Brachiaria brizantha cv. BRS Piata), and performance of Nellore
      heifers in agrosilvopastoral systems (ASPS) with three eucalyptus (Eucalyptus
      urograndis) tree densities, during winter, spring, summer, and fall. Three
      integrated systems were evaluated: ASPS-1 (357 trees ha(-1)), ASPS-2 (227 trees
      ha(-1)), and CON (5 trees ha(-1)). In each system, two sward heights were
      evaluated: short and tall. A total of 80 11-month-old Nellore heifers were
      randomly allocated in a randomized split-plot block, 3 * 2 factorial. Greater dry
      matter availability was observed on CON pastures during the fall season. Greater
      percentage of leaf lamina was detected on ASPS-1 with short sward height and
      greater during summer, compared with other seasons. A greater forage production
      was observed between tree rows and for tall sward height. Spring was the season
      with less forage nutritive value. Average daily gain was greater during summer
      and fall. Gain per hectare and stocking rate were greater on CON system and on
      ASPS-2. Pastures with short sward height had greater gain per hectare and
      stocking rate. Agrosilvopastoral systems with intermediate tree density seem to
      be a good choice for producers willing to diversify their revenue sources without
      decreasing animal production. 

PMID- 24043418
TI  - Imported Plasmodium falciparum malaria in Istanbul, Turkey: risk factors for
      severe course and mortality.
AB  - We describe the epidemiological, clinical features and risk factors for the
      morbidity and mortality of imported Plasmodium falciparum malaria cases during
      the last 10 years in Istanbul, Turkey. The epidemiological, clinical and
      laboratory data of cases in six tertiary care hospitals in Istanbul between 2002
      and 2012 were analysed. Seventy patients (65 males, five females; median age 37;
      range: 14-84) were included. Sixty-five (93%) patients had travelled to African
      countries and the remaining five to other malarious countries. Seventeen (24%)
      had a history of previous malarial episodes; eight (13%) developed recrudescence
      during the first month; 22 (31%), 17 (24%), 20 (29%) and three (4%) cases had
      cerebral malaria, cholestatic icterus, malarial hepatitis and respiratory
      distress syndrome on admission, respectively. Six of 12 patients with severe
      falciparum malaria died. Clinically, the presence of alteration in mental status,
      icterus, hypoglycaemia, disseminated intravascular coagulation and malarial
      hepatitis were statistically significant for the development of severe malaria
      and mortality. Recrudescence should not be forgotten, especially in uncomplicated
      cases. 

PMID- 24043419
TI  - Fuzzy sampled-data control for uncertain vehicle suspension systems.
AB  - This paper investigates the problem of sampled-data Hinfinity control of
      uncertain active suspension systems via fuzzy control approach. Our work focuses
      on designing state-feedback and output-feedback sampled-data controllers to
      guarantee the resulting closed-loop dynamical systems to be asymptotically stable
      and satisfy Hinfinity disturbance attenuation level and suspension performance
      constraints. Using Takagi-Sugeno (T-S) fuzzy model control method, T-S fuzzy
      models are established for uncertain vehicle active suspension systems
      considering the desired suspension performances. Based on Lyapunov stability
      theory, the existence conditions of state-feedback and output-feedback sampled
      data controllers are obtained by solving an optimization problem. Simulation
      results for active vehicle suspension systems with uncertainty are provided to
      demonstrate the effectiveness of the proposed method. 

PMID- 24043420
TI  - A biodynamic feedthrough model based on neuromuscular principles.
AB  - A biodynamic feedthrough (BDFT) model is proposed that describes how vehicle
      accelerations feed through the human body, causing involuntary limb motions and
      so involuntary control inputs. BDFT dynamics strongly depend on limb dynamics,
      which can vary between persons (between-subject variability), but also within one
      person over time, e.g., due to the control task performed (within-subject
      variability). The proposed BDFT model is based on physical neuromuscular
      principles and is derived from an established admittance model-describing limb
      dynamics-which was extended to include control device dynamics and account for
      acceleration effects. The resulting BDFT model serves primarily the purpose of
      increasing the understanding of the relationship between neuromuscular admittance
      and biodynamic feedthrough. An added advantage of the proposed model is that its
      parameters can be estimated using a two-stage approach, making the parameter
      estimation more robust, as the procedure is largely based on the well documented
      procedure required for the admittance model. To estimate the parameter values of
      the BDFT model, data are used from an experiment in which both neuromuscular
      admittance and biodynamic feedthrough are measured. The quality of the BDFT model
      is evaluated in the frequency and time domain. Results provide strong evidence
      that the BDFT model and the proposed method of parameter estimation put forward
      in this paper allows for accurate BDFT modeling across different subjects
      (accounting for between-subject variability) and across control tasks (accounting
      for within-subject variability). 

PMID- 24043421
TI  - A library of functional recombinant cell-surface and secreted P. falciparum
      merozoite proteins.
AB  - Malaria, an infectious disease caused by parasites of the Plasmodium genus, is
      one of the world's major public health concerns causing up to a million deaths
      annually, mostly because of P. falciparum infections. All of the clinical
      symptoms are associated with the blood stage of the disease, an obligate part of
      the parasite life cycle, when a form of the parasite called the merozoite
      recognizes and invades host erythrocytes. During erythrocyte invasion, merozoites
      are directly exposed to the host humoral immune system making the blood stage of
      the parasite a conceptually attractive therapeutic target. Progress in the
      functional and molecular characterization of P. falciparum merozoite proteins,
      however, has been hampered by the technical challenges associated with expressing
      these proteins in a biochemically active recombinant form. This challenge is
      particularly acute for extracellular proteins, which are the likely targets of
      host antibody responses, because they contain structurally critical post
      translational modifications that are not added by some recombinant expression
      systems. Here, we report the development of a method that uses a mammalian
      expression system to compile a protein resource containing the entire ectodomains
      of 42 P. falciparum merozoite secreted and cell surface proteins, many of which
      have not previously been characterized. Importantly, we are able to recapitulate
      known biochemical activities by showing that recombinant MSP1-MSP7 and P12-P41
      directly interact, and that both recombinant EBA175 and EBA140 can bind human
      erythrocytes in a sialic acid-dependent manner. Finally, we use sera from malaria
      exposed immune adults to profile the relative immunoreactivity of the proteins
      and show that the majority of the antigens contain conformational (heat-labile)
      epitopes. We envisage that this resource of recombinant proteins will make a
      valuable contribution toward a molecular understanding of the blood stage of P.
      falciparum infections and facilitate the comparative screening of antigens as
      blood-stage vaccine candidates. 

PMID- 24043422
TI  - Coomassie blue as a near-infrared fluorescent stain: a systematic comparison with
      Sypro Ruby for in-gel protein detection.
AB  - Quantitative proteome analyses suggest that the well-established stain colloidal
      Coomassie Blue, when used as an infrared dye, may provide sensitive, post
      electrophoretic in-gel protein detection that can rival even Sypro Ruby.
      Considering the central role of two-dimensional gel electrophoresis in top-down
      proteomic analyses, a more cost effective alternative such as Coomassie Blue
      could prove an important tool in ongoing refinements of this important analytical
      technique. To date, no systematic characterization of Coomassie Blue infrared
      fluorescence detection relative to detection with SR has been reported. Here,
      seven commercial Coomassie stain reagents and seven stain formulations described
      in the literature were systematically compared. The selectivity, threshold
      sensitivity, inter-protein variability, and linear-dynamic range of Coomassie
      Blue infrared fluorescence detection were assessed in parallel with Sypro Ruby.
      Notably, several of the Coomassie stain formulations provided infrared
      fluorescence detection sensitivity to <1 ng of protein in-gel, slightly exceeding
      the performance of Sypro Ruby. The linear dynamic range of Coomassie Blue
      infrared fluorescence detection was found to significantly exceed that of Sypro
      Ruby. However, in two-dimensional gel analyses, because of a blunted fluorescence
      response, Sypro Ruby was able to detect a few additional protein spots, amounting
      to 0.6% of the detected proteome. Thus, although both detection methods have
      their advantages and disadvantages, differences between the two appear to be
      small. Coomassie Blue infrared fluorescence detection is thus a viable
      alternative for gel-based proteomics, offering detection comparable to Sypro
      Ruby, and more reliable quantitative assessments, but at a fraction of the cost. 

PMID- 24043423
TI  - Characterization of native protein complexes and protein isoform variation using
      size-fractionation-based quantitative proteomics.
AB  - Proteins form a diverse array of complexes that mediate cellular function and
      regulation. A largely unexplored feature of such protein complexes is the
      selective participation of specific protein isoforms and/or post-translationally
      modified forms. In this study, we combined native size-exclusion chromatography
      (SEC) with high-throughput proteomic analysis to characterize soluble protein
      complexes isolated from human osteosarcoma (U2OS) cells. Using this approach, we
      have identified over 71,500 peptides and 1,600 phosphosites, corresponding to
      over 8,000 proteins, distributed across 40 SEC fractions. This represents >50% of
      the predicted U2OS cell proteome, identified with a mean peptide sequence
      coverage of 27% per protein. Three biological replicates were performed, allowing
      statistical evaluation of the data and demonstrating a high degree of
      reproducibility in the SEC fractionation procedure. Specific proteins were
      detected interacting with multiple independent complexes, as typified by the
      separation of distinct complexes for the MRFAP1-MORF4L1-MRGBP interaction
      network. The data also revealed protein isoforms and post-translational
      modifications that selectively associated with distinct subsets of protein
      complexes. Surprisingly, there was clear enrichment for specific Gene Ontology
      terms associated with differential size classes of protein complexes. This study
      demonstrates that combined SEC/MS analysis can be used for the system-wide
      annotation of protein complexes and to predict potential isoform-specific
      interactions. All of these SEC data on the native separation of protein complexes
      have been integrated within the Encyclopedia of Proteome Dynamics, an online,
      multidimensional data-sharing resource available to the community. 

PMID- 24043424
TI  - Transcriptomic messiness in the venom duct of Conus miles contributes to
      conotoxin diversity.
AB  - Marine cone snails have developed sophisticated chemical strategies to capture
      prey and defend themselves against predators. Among the vast array of bioactive
      molecules in their venom, peptide components called conotoxins or conopeptides
      dominate, with many binding with high affinity and selectivity to a broad range
      of cellular targets, including receptors and transporters of the nervous system.
      Whereas the conopeptide gene precursor organization has a conserved topology, the
      peptides in the venom duct are highly processed. Indeed, deep sequencing
      transcriptomics has uncovered on average fewer than 100 toxin gene precursors per
      species, whereas advanced proteomics has revealed >10-fold greater diversity at
      the peptide level. In the present study, second-generation sequencing
      technologies coupled to highly sensitive mass spectrometry methods were applied
      to rapidly uncover the conopeptide diversity in the venom of a worm-hunting
      species, Conus miles. A total of 662 putative conopeptide encoded sequences were
      retrieved from transcriptomic data, comprising 48 validated conotoxin sequences
      that clustered into 10 gene superfamilies, including 3 novel superfamilies and a
      novel cysteine framework (C-C-C-CCC-C-C) identified at both transcript and
      peptide levels. A surprisingly large number of conopeptide gene sequences were
      expressed at low levels, including a series of single amino acid variants, as
      well as sequences containing deletions and frame and stop codon shifts. Some of
      the toxin variants generate alternative cleavage sites, interrupted or elongated
      cysteine frameworks, and highly variable isoforms within families that could be
      identified at the peptide level. Together with the variable peptide processing
      identified previously, background genetic and phenotypic levels of biological
      messiness in venoms contribute to the hypervariability of venom peptides and
      their ability to evolve rapidly. 

PMID- 24043425
TI  - Neutron-encoded signatures enable product ion annotation from tandem mass
      spectra.
AB  - We report the use of neutron-encoded (NeuCode) stable isotope labeling of amino
      acids in cell culture for the purpose of C-terminal product ion annotation. Two
      NeuCode labeling isotopologues of lysine, (13)C6(15)N2 and (2)H8, which differ by
      36 mDa, were metabolically embedded in a sample proteome, and the resultant
      labeled proteins were combined, digested, and analyzed via liquid chromatography
      and mass spectrometry. With MS/MS scan resolving powers of ~50,000 or higher,
      product ions containing the C terminus (i.e. lysine) appear as a doublet spaced
      by exactly 36 mDa, whereas N-terminal fragments exist as a single m/z peak.
      Through theory and experiment, we demonstrate that over 90% of all y-type product
      ions have detectable doublets. We report on an algorithm that can extract these
      neutron signatures with high sensitivity and specificity. In other words, of
      15,503 y-type product ion peaks, the y-type ion identification algorithm
      correctly identified 14,552 (93.2%) based on detection of the NeuCode doublet;
      6.8% were misclassified (i.e. other ion types that were assigned as y-type
      products). Searching NeuCode labeled yeast with PepNovo(+) resulted in a 34%
      increase in correct de novo identifications relative to searching through MS/MS
      only. We use this tool to simplify spectra prior to database searching, to sort
      unmatched tandem mass spectra for spectral richness, for correlation of co
      fragmented ions to their parent precursor, and for de novo sequence
      identification.

PMID- 24043426
TI  - 6-thioguanine induces mitochondrial dysfunction and oxidative DNA damage in acute
      lymphoblastic leukemia cells.
AB  - Thiopurines are among the most successful chemotherapeutic agents used for
      treating various human diseases, including acute lymphoblastic leukemia and
      chronic inflammation. Although metabolic conversion and the subsequent
      incorporation of 6-thioguanine ((S)G) nucleotides into nucleic acids are
      considered important for allowing the thiopurine drugs to induce their cytotoxic
      effects, alternative mechanisms may also exist. We hypothesized that an unbiased
      analysis of (S)G-induced perturbation of the entire proteome might uncover novel
      mechanism(s) of action of the drug. We performed a quantitative assessment of
      global protein expression in control and (S)G-treated Jurkat T cells by employing
      stable isotope labeling by amino acids in cell culture and liquid chromatography
      tandem mass spectrometry (LC-MS/MS) analysis. LC-MS/MS quantification results
      uncovered substantially decreased expression of a large number of proteins in the
      mitochondrial respiratory chain complex, and Ingenuity Pathway Analysis of the
      significantly altered proteins showed that (S)G treatment induced mitochondrial
      dysfunction. This was accompanied by diminished uptake of MitoTracker Deep Red
      and the elevated formation of oxidatively induced DNA lesions, including 8,5'
      cyclo-2'-deoxyadenosine and 8,5'-cyclo-2'-deoxyguanosine. Together, our results
      suggested that (S)G may exert its cytotoxic effect by inducing mitochondrial
      dysfunction and reactive oxygen species formation in acute lymphoblastic leukemia
      cells. 

PMID- 24043427
TI  - Stable isotope metabolic labeling-based quantitative phosphoproteomic analysis of
      Arabidopsis mutants reveals ethylene-regulated time-dependent phosphoproteins and
      putative substrates of constitutive triple response 1 kinase.
AB  - Ethylene is an important plant hormone that regulates numerous cellular processes
      and stress responses. The mode of action of ethylene is both dose- and time
      dependent. Protein phosphorylation plays a key role in ethylene signaling, which
      is mediated by the activities of ethylene receptors, constitutive triple response
      1 (CTR1) kinase, and phosphatase. To address how ethylene alters the cellular
      protein phosphorylation profile in a time-dependent manner, differential and
      quantitative phosphoproteomics based on (15)N stable isotope labeling in
      Arabidopsis was performed on both one-minute ethylene-treated Arabidopsis
      ethylene-overly-sensitive loss-of-function mutant rcn1-1, deficient in PP2A
      phosphatase activity, and a pair of long-term ethylene-treated wild-type and loss
      of-function ethylene signaling ctr1-1 mutants, deficient in mitogen-activated
      kinase kinase kinase activity. In total, 1079 phosphopeptides were identified,
      among which 44 were novel. Several one-minute ethylene-regulated phosphoproteins
      were found from the rcn1-1. Bioinformatic analysis of the rcn1-1 phosphoproteome
      predicted nine phosphoproteins as the putative substrates for PP2A phosphatase.
      In addition, from CTR1 kinase-enhanced phosphosites, we also found putative CTR1
      kinase substrates including plastid transcriptionally active protein and calcium
      sensing receptor. These regulatory proteins are phosphorylated in the presence of
      ethylene. Analysis of ethylene-regulated phosphosites using the group-based
      prediction system with a protein-protein interaction filter revealed a total of
      14 kinase-substrate relationships that may function in both CTR1 kinase- and PP2A
      phosphatase-mediated phosphor-relay pathways. Finally, several ethylene-regulated
      post-translational modification network models have been built using molecular
      systems biology tools. It is proposed that ethylene regulates the phosphorylation
      of arginine/serine-rich splicing factor 41, plasma membrane intrinsic protein 2A,
      light harvesting chlorophyll A/B binding protein 1.1, and flowering bHLH 3
      proteins in a dual-and-opposing fashion. 

PMID- 24043428
TI  - Vegetable protein and vegetable fat intakes in pre-adolescent and adolescent
      girls, and risk for benign breast disease in young women.
AB  - Previous investigations, of adolescent diet recalled in adulthood, found lower
      risk for benign breast disease (BBD) with higher intakes of vegetable fat and
      nuts during high school. We investigate whether vegetable protein and fat,
      derived from diets reported during pre-adolescence and adolescence, are
      associated with subsequent risk for BBD in young women. The Growing Up Today
      Study includes 9,039 females, 9-15 years in 1996, who completed questionnaires
      annually through 2001, and then in 2003, 2005, 2007, and 2010. Food frequency
      questionnaires (1996-2001) obtained intake data on a variety of foods. Beginning
      in 2005, women (18-30 years) reported whether they had ever been diagnosed with
      BBD that was confirmed by breast biopsy (n = 112 cases). Logistic regression
      estimated associations between intakes of vegetable protein and fat and biopsy
      confirmed BBD. Those individual foods that were the largest contributors of
      protein and fat in this cohort were also investigated. In analyses of intakes
      from 1996 through 1998, when our cohort was youngest, vegetable fat (OR =
      0.72/(10 gm/day), 95 % CI 0.53-0.98; p = 0.04) was inversely associated with BBD
      risk. The greatest sources of vegetable fat and protein in these girls were
      peanut butter, peanuts, nuts, beans (beans, lentils, and soybeans), and corn. A
      daily serving of any one of these was associated with lower risk (OR =
      0.32/(serv/day), 95 % CI 0.13-0.79; p = 0.01). Peanut butter (and nuts) at age 11
      years was inversely associated with risk (p = 0.01). In analyses of intakes at
      age 14 years, vegetable protein was associated with lower BBD risk (OR = 0.64/(10
      gm/day), 95 % CI 0.43-0.95; p = 0.03). A daily serving at 14 years of any one of
      the foods was associated with lower risk (OR = 0.34, 95 % CI 0.16-0.75; p =
      0.01), as was peanut butter (and nuts) (p = 0.02). Girls with a family history of
      breast cancer had significantly lower risk if they consumed these foods or
      vegetable fat. In conclusion, consumption of vegetable protein, fat, peanut
      butter, or nuts by older girls may help reduce their risk of BBD as young women.

PMID- 24043429
TI  - An experimental model of partial insulin-like growth factor-1 deficiency in mice.
AB  - Insulin-like growth factor-1 (IGF-1) is responsible for many systemic growth
      hormone (GH) functions although it has an extensive number of inherent activities
      (anabolic, cytoprotective, and anti-inflammatory). The potential options for IGF
      1 therapy arise as a promising strategy in a wide list of human diseases.
      However, deeper studies are needed from a suitable animal model. All human
      conditions of IGF-1 deficiency consist in partially decreased IGF-1 levels since
      total absence of this hormone is hardly compatible with life. The aim of this
      work was to confirm that heterozygous Igf-1 (+/-) mice (Hz) may be considered as
      an appropriate animal model to study conditions of IGF-1 deficiency, focusing on
      early ages. Heterozygous Igf-1 (+/-) mice were compared to homozygous Igf-1 (+/+)
      by assessing gene expression by quantitative PCR, serum circulating levels by
      ELISA, and tissue staining. Compared to controls, Hz mice (25 days old) showed a
      partial but significant reduction of IGF-1 circulating levels, correlating with a
      reduced body weight and diminished serum IGFBP-3 levels. Hz mice presented a
      significant decrease of IGF-1 gene expression in related organs (liver, bone,
      testicles, and brain) while IGF-1 receptor showed a normal expression. However,
      gene expression of growth hormone receptor (GHR) was increased in the liver but
      reduced in the bone, testicles, and brain. In addition, a significant reduction
      of cortical bone thickness and histopathological alterations in the testicles
      were found in Hz mice when compared to controls. Finally, the lifelong evolution
      of IGF-1 serum levels showed significant differences throughout life until aging
      in mice. Results in this paper provide evidence for considering heterozygous mice
      as a suitable experimental model, from early stages, to get more insight into the
      mechanisms of the beneficial actions induced by IGF-1 replacement therapy.

PMID- 24043430
TI  - Identification and field evaluation of non-host volatiles disturbing host
      location by the tea geometrid, Ectropis obliqua.
AB  - Volatile organic compounds derived from non-host plants, Ocimum basilicum,
      Rosmarinus officinalis, Corymbia citriodora, and Ruta graveolens, can be used to
      mask host plant odors, and are repellent to the tea geometrid, Ectropis obliqua.
      Volatile compounds were collected by headspace absorption, and the components
      were identified and quantified by using gas chromatography/mass spectrometry. The
      responses of antennae of female E. obliqua to the compounds were evaluated with
      gas chromatography/electroantennography detection. Qualitative and quantitative
      differences were found among the four odor profiles. Consistent
      electroantennographic activity was obtained for eight of the volatiles from the
      four plants: beta-myrcene, alpha-terpinene, gamma-terpinene, linalool, cis
      verbenol, camphor, alpha-terpineol, and verbenone. In a Y-tube bioassay, six
      chemicals, beta-myrcene, gamma-terpinene, (R)-(-)-linalool, (S)-(-)-cis-verbenol,
      (R)-(+)-camphor, and (S)-(-)-verbenone, were the main compounds responsible for
      repelling E. obliqua. An eight-component mixture including all of the bioactive
      compounds (in a ratio of 13:2:13:8:1:24:6:17) from R. officinalis was
      significantly more effective at repelling the moths than any single compound or a
      mixture of equal amounts of the eight compounds. Field results demonstrated that
      intercropping tea plants with R. officinalis effectively suppressed E. obliqua
      infestations in a tea plantation. Our findings suggests that odor blends of R.
      officinalis play a role in disturbing host orientation behavior, and in repelling
      E. obliqua adults, and that R. officinalis should be considered when developing
      "push-pull" strategies aimed at optimizing the control of E. obliqua with
      semiochemicals. 

PMID- 24043431
TI  - CORR Insights (r): Does research participation make a difference in residency
      training?

PMID- 24043432
TI  - Rotator cuff tear and glenohumeral instability : a systematic review.
AB  - BACKGROUND: The rotator cuff plays a significant role in the static and dynamic
      stability of the glenohumeral joint. Rotator cuff tears may occur after shoulder
      dislocations, whether in younger athletes or older patients with age-related
      tendon degeneration. Untreated tears may cause persistent pain, dysfunction,
      instability, and degenerative changes. A thorough understanding of when to look
      for rotator cuff tears after shoulder dislocations and how best to manage them
      may decrease patients' pain and improve function. QUESTIONS/PURPOSES: We
      systematically reviewed the available literature to better understand (1) when a
      rotator cuff tear should be suspected after a dislocation, (2) whether surgical
      or nonsurgical approaches result in better scores for pain and satisfaction in
      patients with rotator cuff tears resulting from shoulder dislocations, and (3)
      whether intraarticular lesions, rotator cuff tears, or both should be addressed
      when surgery is performed. METHODS: We systematically searched MEDLINE((r)),
      CINAHL, and EMBASE for studies published from 1950 to 2012. We included studies
      reporting outcomes after treatment in patients with rotator cuff tears and
      shoulder dislocations. We excluded case reports, studies without any treatment,
      and studies about patients treated with arthroplasty. Five Level III and six
      Level IV studies were ultimately selected for review. RESULTS: Patients with
      persistent pain or dysfunction after a shoulder dislocation often had a
      concomitant rotator cuff tear. Surgical repair resulted in improved pain relief
      and patient satisfaction compared to nonoperative management. Repair of the
      rotator cuff, along with concomitant capsulolabral lesions, helped restore
      shoulder stability. While these findings are based on Level III and IV evidence,
      better long-term studies with larger cohorts are needed to strengthen evidence
      based recommendations. CONCLUSIONS: Persistent pain and dysfunction after a
      shoulder dislocation should prompt evaluation of the rotator cuff, especially in
      contact or overhead athletes, patients older than 40 years, or those with nerve
      injury. Surgery should be considered in the appropriately active patient with a
      rotator cuff tear after dislocation. While the current literature suggests
      improved stability and function after surgical repair of the rotator cuff, higher
      quality prospective studies are necessary to make definitive conclusions.

PMID- 24043433
TI  - Tiotropium versus ipratropium bromide for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Tiotropium and ipratropium bromide are both recognised treatments in
      the management of people with stable chronic obstructive pulmonary disease
      (COPD). There are new studies which have compared tiotropium with ipratropium
      bromide, making an update necessary. OBJECTIVES: To compare the relative effects
      of tiotropium to ipratropium bromide on markers of quality of life,
      exacerbations, symptoms, lung function and serious adverse events in patients
      with COPD using available randomised controlled trial (RCT) data. SEARCH METHODS:
      We identified RCTs from the Cochrane Airways Group Specialised Register of trials
      (CAGR) and ClinicalTrials.gov up to November 2012. SELECTION CRITERIA: We
      included parallel group RCTs of 12 weeks duration or longer comparing treatment
      with tiotropium with ipratropium bromide for patients with stable COPD. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed studies for
      inclusion and then extracted data on study quality and outcome results. We
      contacted trial sponsors for additional information. We analysed the data using
      Cochrane Review Manager (RevMan 5.2). MAIN RESULTS: This review included two
      studies of good methodological quality that enrolled 1073 participants with COPD.
      The studies used a similar design and inclusion criteria and were of at least 12
      weeks duration; the participants had a mean forced expiratory volume in one
      second (FEV1) of 40% predicted value at baseline. One study used tiotropium via
      the HandiHaler (18 ug) for 12 months and the other via the Respimat device (5 ug
      and 10 ug) for 12 weeks. In general, the treatment groups were well matched at
      baseline but not all outcomes were reported for both studies. Overall the risk of
      bias across the included RCTs was low.For primary outcomes this review found that
      at the three months trough (the lowest level measured before treatment) FEV1
      significantly increased with tiotropium compared to ipratropium bromide (mean
      difference (MD) 109 mL; 95% confidence interval (CI) 81 to 137, moderate quality
      evidence, I(2) = 62%). There were fewer people experiencing one or more non-fatal
      serious adverse events on tiotropium compared to ipratropium (odds ratio (OR)
      0.5; 95% CI 0.34 to 0.73, high quality evidence). This represents an absolute
      reduction in risk from 176 to 97 per 1000 people over three to 12 months.
      Concerning disease specific adverse events, the tiotropium group were also less
      likely to experience a COPD-related serious adverse event when compared to
      ipratropium bromide (OR 0.59; 95% CI 0.41 to 0.85, moderate quality evidence).For
      secondary outcomes, both studies reported fewer hospital admissions in the
      tiotropium group (OR 0.34; 95% CI 0.15 to 0.70, moderate quality evidence); as
      well as fewer patients experiencing one or more exacerbations leading to
      hospitalisation in the people on tiotropium in both studies (OR 0.56; 95% CI 0.31
      to 0.99, moderate quality evidence). There was no significant difference in
      mortality between the treatments (OR 1.39; 95% CI 0.44 to 4.39, moderate quality
      evidence). One study measured quality of life using the St George's Respiratory
      Questionnaire (SGRQ); the mean SGRQ score at 52 weeks was lower in the tiotropium
      group than the ipratropium group (lower on the scale is favourable) (MD -3.30;
      95% CI -5.63 to -0.97, moderate quality evidence). There were fewer participants
      suffering one of more exacerbations in the tiotropium arm (OR 0.71; 95% CI 0.52
      to 0.95, high quality evidence) and there was also a reported difference in the
      mean number of exacerbations per person per year which reached statistical
      significance (MD -0.23; 95% CI -0.39 to -0.07, P = 0.006, moderate quality
      evidence). From the 1073 participants there were significantly fewer withdrawals
      from the tiotropium group (OR 0.58; 95% CI 0.41 to 0.83, high quality evidence).
      AUTHORS' CONCLUSIONS: This review shows that tiotropium treatment, when compared
      with ipratropium bromide, was associated with improved lung function, fewer
      hospital admissions (including those for exacerbations of COPD), fewer
      exacerbations of COPD and improved quality of life. There were both fewer serious
      adverse events and disease specific events in the tiotropium group, but no
      significant difference in deaths with ipratropium bromide when compared to
      tiotropium. Thus, tiotropium appears to be a reasonable choice (instead of
      ipratropium bromide) for patients with stable COPD, as proposed in guidelines. We
      would advise some caution with tiotropium via the Respimat inhaler and suggest
      waiting for further information from an ongoing head-to-head trial comparing
      mortality in relation to tiotropium delivery devices and doses.

PMID- 24043434
TI  - Invited commentary: How can we reconcile the findings of Keyes et al.'s study
      with the experience of our patients in clinical practice?
AB  - Although the accompanying study by Keyes et al. (Am J Epidemiol. 2013;178(9):1378
      1388) shows us that women currently using hormonal contraception (HC) have better
      scores on the Center for Epidemiologic Studies Depression Scale and report fewer
      suicide attempts, it does not show us that HC protects women from mood disorders
      or that HC is free of the mood-related side effects which cause high rates of
      discontinuation. The groups compared in the Keyes et al. study were different in
      many ways; the women using HC were younger, were more likely to engage in
      positive health behaviors, and had lower depression scores at each prior
      interview. Women with mood disorders are more likely to avoid or discontinue HC
      and more likely to experience worsening mood while on HC. The negative mood
      related side effects experienced by women using HC (irritability and lability)
      are not captured by a screening tool for clinical depression, such as the
      depression scale used in this study. The database used in this study was
      longitudinal and multiwave, so the authors could have compared changes in
      depressive symptoms among women who switched from hormonal to nonhormonal
      contraceptive methods (and vice versa) across different waves. Only if the same
      women experienced greater levels of depressive symptoms after discontinuing HC
      and fewer symptoms when they restarted HC could we conclude that HC may protect
      women from mood disorders.

PMID- 24043435
TI  - Invited commentary: extremely low-frequency magnetic fields and breast cancer-
      now it is enough!
AB  - Research on an association between extremely low frequency (ELF) magnetic fields
      and breast cancer has been conducted since the 1980s, based on the hypothesis
      that ELF fields suppress melatonin production and melatonin protects against
      breast cancer development. In this issue of the Journal, Li et al. (Am J
      Epidemiol. 2013;178(7):1038-1045) present a well-designed study on occupational
      exposure to ELF fields and breast cancer that adds to the already large pool of
      data that has not supported the hypothesis. Over time, the quality and
      statistical power of studies within this research area have increased
      considerably, and advances in exposure assessment have reduced exposure
      misclassification. The evidence is consistently negative. A World Health
      Organization health risk assessment concluded in 2005 that the evidence from
      experimental and epidemiologic studies is sufficient to give confidence that ELF
      magnetic fields do not cause breast cancer. The new study adds even more
      confidence to this conclusion. We should now focus our time and research
      resources on more promising hypotheses, the results of which could make a
      difference for public health and advance science. Further epidemiologic studies
      on ELF fields and breast cancer are likely to have little new knowledge to add. 

PMID- 24043436
TI  - Exposure-response analysis and risk assessment for lung cancer in relationship to
      silica exposure: a 44-year cohort study of 34,018 workers.
AB  - Crystalline silica has been classified as a human carcinogen by the International
      Agency for Research on Cancer (Lyon, France); however, few previous studies have
      provided quantitative data on silica exposure, silicosis, and/or smoking. We
      investigated a cohort in China (in 1960-2003) of 34,018 workers without exposure
      to carcinogenic confounders. Cumulative silica exposure was estimated by linking
      a job-exposure matrix to work history. Cox proportional hazards model was used to
      conduct exposure-response analysis and risk assessment. During a mean 34.5-year
      follow-up, 546 lung cancer deaths were identified. Categorical analyses by
      quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard
      ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed
      group. Monotonic exposure-response trends were observed among nonsilicotics (P
      for trend < 0.001). Analyses using splines showed similar trends. The joint
      effect of silica and smoking was more than additive and close to multiplicative.
      For workers exposed from ages 20 to 65 years at 0.1 mg/m(3) of silica exposure,
      the estimated excess lifetime risk (through age 75 years) was 0.51%. These
      findings confirm silica as a human carcinogen and suggest that current exposure
      limits in many countries might be insufficient to protect workers from lung
      cancer. They also indicate that smoking cessation could help reduce lung cancer
      risk for silica-exposed individuals.

PMID- 24043437
TI  - A new framework and software to estimate time-varying reproduction numbers during
      epidemics.
AB  - The quantification of transmissibility during epidemics is essential to designing
      and adjusting public health responses. Transmissibility can be measured by the
      reproduction number R, the average number of secondary cases caused by an
      infected individual. Several methods have been proposed to estimate R over the
      course of an epidemic; however, they are usually difficult to implement for
      people without a strong background in statistical modeling. Here, we present a
      ready-to-use tool for estimating R from incidence time series, which is
      implemented in popular software including Microsoft Excel (Microsoft Corporation,
      Redmond, Washington). This tool produces novel, statistically robust analytical
      estimates of R and incorporates uncertainty in the distribution of the serial
      interval (the time between the onset of symptoms in a primary case and the onset
      of symptoms in secondary cases). We applied the method to 5 historical outbreaks;
      the resulting estimates of R are consistent with those presented in the
      literature. This tool should help epidemiologists quantify temporal changes in
      the transmission intensity of future epidemics by using surveillance data.

PMID- 24043438
TI  - Keyes et Al. Respond to "hormonal contraception and mood".

PMID- 24043439
TI  - Occupational exposure to magnetic fields and breast cancer among women textile
      workers in Shanghai, China.
AB  - Exposure to magnetic fields (MFs) is hypothesized to increase the risk of breast
      cancer by reducing production of melatonin by the pineal gland. A nested case
      cohort study was conducted to investigate the association between occupational
      exposure to MFs and the risk of breast cancer within a cohort of 267,400 female
      textile workers in Shanghai, China. The study included 1,687 incident breast
      cancer cases diagnosed from 1989 to 2000 and 4,702 noncases selected from the
      cohort. Subjects' complete work histories were linked to a job-exposure matrix
      developed specifically for the present study to estimate cumulative MF exposure.
      Hazard ratios and 95% confidence intervals were calculated using Cox proportional
      hazards modeling that was adapted for the case-cohort design. Hazard ratios were
      estimated in relation to cumulative exposure during a woman's entire working
      years. No association was observed between cumulative exposure to MFs and overall
      risk of breast cancer. The hazard ratio for the highest compared with the lowest
      quartile of cumulative exposure was 1.03 (95% confidence interval: 0.87, 1.21).
      Similar null findings were observed when exposures were lagged and stratified by
      age at breast cancer diagnosis. The findings do not support the hypothesis that
      MF exposure increases the risk of breast cancer. 

PMID- 24043440
TI  - Association of hormonal contraceptive use with reduced levels of depressive
      symptoms: a national study of sexually active women in the United States.
AB  - An estimated 80% of sexually active young women in the United States use hormonal
      contraceptives during their reproductive years. Associations between hormonal
      contraceptive use and mood disturbances remain understudied, despite the
      hypothesis that estrogen and progesterone play a role in mood problems. In this
      study, we used data from 6,654 sexually active nonpregnant women across 4 waves
      of the National Longitudinal Study of Adolescent Health (1994-2008), focusing on
      women aged 25-34 years. Women were asked about hormonal contraceptive use in the
      context of a current sexual partnership; thus, contraceptive users were compared
      with other sexually active women who were using either nonhormonal contraception
      or no contraception. Depressive symptoms were assessed with the Center for
      Epidemiologic Studies Depression Scale. At ages 25-34 years, hormonal
      contraceptive users had lower mean levels of concurrent depressive symptoms (beta
      = -1.04, 95% confidence interval: -1.73, -0.35) and were less likely to report a
      past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14,
      0.95) than women using low-efficacy contraception or no contraception, in models
      adjusted for propensity scores for hormonal contraceptive use. Longitudinal
      analyses indicated that associations between hormonal contraception and
      depressive symptoms were stable. Hormonal contraception may reduce levels of
      depressive symptoms among young women. Systematic investigation of exogenous
      hormones as a potential preventive factor in psychiatric epidemiology is
      warranted.

PMID- 24043441
TI  - P53 protein in proliferation, repair and apoptosis of cells.
AB  - The p53 protein is an important factor of many intra- and extracellular
      processes. This protein regulates the repair of cellular DNA and induces
      apoptosis. It is also responsible for the regulation of the senescence and the
      cell entering the subsequent stages of the cellular cycle. The protein p53 is
      also involved in inhibiting angiogenesis and the induction of oxidative shock. In
      our study, we examined the activity of p53 protein in the uterine epithelial
      cells in rats treated with cladribine. Its action is mainly based on apoptosis
      induction. We compared the activity of p53 protein in cells with a high apoptosis
      index and in cells with active repair mechanisms and high proliferation index. We
      observed stronger p53 protein expression in the epithelial cells of the materials
      taken 24 h after the last dose of 2-CdA associated with the active process of
      apoptosis and inhibition of proliferation. After 4 weeks from the last dose of
      cladribine, the stronger expression of p53 protein was associated with both the
      existing changes in the cell's genome, the effects of the ongoing repair
      mechanisms, as well as the high proliferation activity. 

PMID- 24043442
TI  - Soluble TWEAK levels are independently associated with coronary artery disease
      severity in patients with stage 2-3 kidney disease.
AB  - PURPOSE: Patients diagnosed with chronic kidney disease (CKD) have a greater rate
      of cardiovascular mortality compared with the general population. The soluble
      form of TNF-like weak inducer of apoptosis (TWEAK) plays a role in cellular
      proliferation, migration, and apoptosis. The current study aimed to analyze
      whether soluble TWEAK levels are associated with the severity of coronary
      arterial disease (CAD) in CKD patients. METHODS: Ninety-seven patients diagnosed
      with CKD stages 2-3 according to their estimated glomerular filtration rate and
      the presence of kidney injury were included in the study. Plasma sTWEAK
      concentrations were determined using commercially available ELISA kits. Coronary
      angiographies were performed through femoral artery access using the Judkins
      technique. RESULTS: Correlation analysis of sTWEAK and Gensini scores showed
      significant association (p < 0.01, r (2) = 0.287). When patients were divided
      into two groups with a limit of 17 according to their Gensini score, sTWEAK
      levels indicated a statistically significant difference (p < 0.01). CONCLUSIONS:
      Our results indicate a relationship between sTWEAK levels and CAD in CKD stages 2
      3 patients.

PMID- 24043443
TI  - Projected impacts of climate change on environmental suitability for malaria
      transmission in West Africa.
AB  - BACKGROUND: Climate change is expected to affect the distribution of
      environmental suitability for malaria transmission by altering temperature and
      rainfall patterns; however, the local and global impacts of climate change on
      malaria transmission are uncertain. OBJECTIVE: We assessed the effect of climate
      change on malaria transmission in West Africa. METHODS: We coupled a detailed
      mechanistic hydrology and entomology model with climate projections from general
      circulation models (GCMs) to predict changes in vectorial capacity, an indication
      of the risk of human malaria infections, resulting from changes in the
      availability of mosquito breeding sites and temperature-dependent development
      rates. Because there is strong disagreement in climate predictions from different
      GCMs, we focused on the GCM projections that produced the best and worst
      conditions for malaria transmission in each zone of the study area. RESULTS:
      Simulation-based estimates suggest that in the desert fringes of the Sahara,
      vectorial capacity would increase under the worst-case scenario, but not enough
      to sustain transmission. In the transitional zone of the Sahel, climate change is
      predicted to decrease vectorial capacity. In the wetter regions to the south, our
      estimates suggest an increase in vectorial capacity under all scenarios. However,
      because malaria is already highly endemic among human populations in these
      regions, we expect that changes in malaria incidence would be small. CONCLUSION:
      Our findings highlight the importance of rainfall in shaping the impact of
      climate change on malaria transmission in future climates. Even under the GCM
      predictions most conducive to malaria transmission, we do not expect to see a
      significant increase in malaria prevalence in this region.

PMID- 24043445
TI  - Distinct roles of LAFL network genes in promoting the embryonic seedling fate in
      the absence of VAL repression.
AB  - The transition between seed and seedling phases of development is coordinated by
      an interaction between the closely related ABSCISIC ACID-INSENSITIVE3 (ABI3),
      FUSCA3 (FUS3), and LEAFY COTYLEDON2 (LEC2; AFL) and VIVIPAROUS1/ABI3-LIKE (VAL)
      clades of the B3 transcription factor family that respectively activate and
      repress the seed maturation program. In the val1 val2 double mutant, derepression
      of the LEC1, LEC1-LIKE (L1L), and AFL (LAFL) network is associated with
      misexpression of embryonic characteristics resulting in arrested seedling
      development. We show that while the frequency of the embryonic fate in val1 val2
      seedlings depends on the developmental timing of seed rescue, VAL proteins
      repress LAFL genes during germination, but not during seed development.
      Quantitative analysis of LAFL mutants that suppress the val1 val2 seedling
      phenotype revealed distinct roles of LAFL genes in promoting activation of the
      LAFL network. LEC2 and FUS3 are both essential for coordinate activation of the
      network, whereas effects of LEC1, L1L, and ABI3 are additive. Suppression of the
      val1 val2 seedling phenotype by the B3 domain-deficient abi3-12 mutation
      indicates that ABI3 activation of the LAFL network requires the B3 DNA-binding
      domain. In the VAL-deficient background, coordinate regulation of the LAFL
      network is observed over a wide range of genetic and developmental conditions.
      Our findings highlight distinct functional roles and interactions of LAFL network
      genes that are uncovered in the absence of VAL repressors. 

PMID- 24043444
TI  - Feedback inhibition of starch degradation in Arabidopsis leaves mediated by
      trehalose 6-phosphate.
AB  - Many plants accumulate substantial starch reserves in their leaves during the day
      and remobilize them at night to provide carbon and energy for maintenance and
      growth. In this paper, we explore the role of a sugar-signaling metabolite,
      trehalose-6-phosphate (Tre6P), in regulating the accumulation and turnover of
      transitory starch in Arabidopsis (Arabidopsis thaliana) leaves. Ethanol-induced
      overexpression of trehalose-phosphate synthase during the day increased Tre6P
      levels up to 11-fold. There was a transient increase in the rate of starch
      accumulation in the middle of the day, but this was not linked to reductive
      activation of ADP-glucose pyrophosphorylase. A 2- to 3-fold increase in Tre6P
      during the night led to significant inhibition of starch degradation. Maltose and
      maltotriose did not accumulate, suggesting that Tre6P affects an early step in
      the pathway of starch degradation in the chloroplasts. Starch granules isolated
      from induced plants had a higher orthophosphate content than granules from
      noninduced control plants, consistent either with disruption of the
      phosphorylation-dephosphorylation cycle that is essential for efficient starch
      breakdown or with inhibition of starch hydrolysis by beta-amylase. Nonaqueous
      fractionation of leaves showed that Tre6P is predominantly located in the
      cytosol, with estimated in vivo Tre6P concentrations of 4 to 7 um in the cytosol,
      0.2 to 0.5 um in the chloroplasts, and 0.05 um in the vacuole. It is proposed
      that Tre6P is a component in a signaling pathway that mediates the feedback
      regulation of starch breakdown by sucrose, potentially linking starch turnover to
      demand for sucrose by growing sink organs at night. 

PMID- 24043446
TI  - Structural flexibility and functional interaction of Mediator Cdk8 module.
AB  - Mediator is a highly conserved large protein complex (25 proteins, >1000 kDa) and
      preeminently responsible for eukaryotic transcription, which contains a
      dissociable 'Cdk8 module'. Although increasing evidence demonstrates that Cdk8
      module plays both positive and negative roles in transcription regulation, the
      detailed structure, and subunit organization, molecular mechanism how it
      regulates transcription remain elusive. Here we used single-particle electron
      microscopy to characterize the structure and subunit organization of the Cdk8
      module and illuminated the substantial mobility of the Med13 subunit results in
      the structural flexibility. The Cdk8 module interaction with core Mediator is
      concurrent with active transcription in vivo. An interaction with the Cdk8 module
      induces core Mediator into very extended conformation in vitro, which is presumed
      to be an active functional state of Mediator. Taken together, our results
      illuminated the detailed architecture of Cdk8 module, and suggested the Cdk8
      module could positively regulate transcription by modulating Mediator
      conformation. 

PMID- 24043447
TI  - Identification of the chelocardin biosynthetic gene cluster from Amycolatopsis
      sulphurea: a platform for producing novel tetracycline antibiotics.
AB  - Tetracyclines (TCs) are medically important antibiotics from the polyketide
      family of natural products. Chelocardin (CHD), produced by Amycolatopsis
      sulphurea, is a broad-spectrum tetracyclic antibiotic with potent bacteriolytic
      activity against a number of Gram-positive and Gram-negative multi-resistant
      pathogens. CHD has an unknown mode of action that is different from TCs. It has
      some structural features that define it as 'atypical' and, notably, is active
      against tetracycline-resistant pathogens. Identification and characterization of
      the chelocardin biosynthetic gene cluster from A. sulphurea revealed 18 putative
      open reading frames including a type II polyketide synthase. Compared to typical
      TCs, the chd cluster contains a number of features that relate to its
      classification as 'atypical': an additional gene for a putative two-component
      cyclase/aromatase that may be responsible for the different aromatization
      pattern, a gene for a putative aminotransferase for C-4 with the opposite
      stereochemistry to TCs and a gene for a putative C-9 methylase that is a unique
      feature of this biosynthetic cluster within the TCs. Collectively, these enzymes
      deliver a molecule with different aromatization of ring C that results in an
      unusual planar structure of the TC backbone. This is a likely contributor to its
      different mode of action. In addition CHD biosynthesis is primed with acetate,
      unlike the TCs, which are primed with malonamate, and offers a biosynthetic
      engineering platform that represents a unique opportunity for efficient
      generation of novel tetracyclic backbones using combinatorial biosynthesis. 

PMID- 24043449
TI  - Genome shuffling of Aspergillus niger for improving transglycosylation activity.
AB  - Isomaltooligosaccharides (IMO), the glucosylsaccharides used as food additives,
      are made from saccharified starch by enzymes or microbial cells with
      transglycosylation activity. This study aimed to generate shuffled futants of
      Aspergillus niger with enhanced transglycosylation activity for industrial IMO
      production. The starting mutant population was generated by (60)Co-gamma
      radiation; mutants with higher transglycosylation activity were selected and
      subjected to recursive protoplast fusion. The resulting fusants were screened by
      a novel high-throughput method based on detecting non-fermentable reducing sugar.
      After three rounds of genome shuffling, the best performing strain GS3-3 was
      obtained, its transglycosylation activity (14.91 U/mL) was increased by 194.1 %
      compared to that of original strain C-6181. In fermentor test, transglycosylation
      activity of GS3-3 was obtained at 16.61 U/mL. The mycelia of GS3-3 were reused
      ten times to produce IMO syrup from liquefied cassava starch containing about 280
      g/L total sugar within 4 days. The conversion of liquefied cassava starch to IMO
      was at 71.3-72.1 %, which was higher than the best conversion (68 %) ever
      reported. GS3-3 shows a great potential for industrial IMO production.

PMID- 24043450
TI  - Purification and partial characterization of bacillomycin L produced by Bacillus
      amyloliquefaciens K103 from lemon.
AB  - Bacillus amyloliquefaciens K103 isolated from a lemon sample was used as a
      biocontrol agent to suppress Rhizoctonia solani Kuhn and other fungal plant
      pathogens. Two antifungal compounds were purified from the culture broth using
      acid precipitation, gel permeation chromatography, and reversed-phase high
      performance liquid chromatography. Matrix-assisted laser desorption ionization
      time of flight mass spectrometry analysis indicated that the antifungal compounds
      were two isomers similar to bacillomycin L. One of the predominant active
      fractions was subjected to quadrupole time-of-flight mass spectrometry and amino
      acid analysis to determine its structural characteristics, revealing that the
      antifungal compound with a molecular mass of 1,034.5464 was identical to
      bacillomycin L. This is the second report of lemon microflora producing
      bacillomycin L or any antifungal compound, suppressing the growth of R. solani
      Kuhn. Meanwhile, the study provided insights into the enormous potential of food
      microbial resources and bacillomycin L antibiotics in biological control and
      sustainable agriculture. 

PMID- 24043448
TI  - Are HPV vaccination services accessible to high-risk communities? A spatial
      analysis of HPV-associated cancer and Chlamydia rates and safety-net clinics.
AB  - PURPOSE: While HPV vaccines can greatly benefit adolescents and young women from
      high-risk areas, little is known about whether safety-net immunization services
      are geographically accessible to communities at greatest risk for HPV-associated
      diseases. We explore the spatial relationship between areas with high HPV risk
      and proximity to safety-net clinics from an ecologic perspective. METHODS: We
      used cancer registry data and Chlamydia surveillance data to identify
      neighborhoods within Los Angeles County with high risk for HPV-associated
      cancers. We examined proximity to safety-net clinics among neighborhoods with the
      highest risk. Proximity was measured as the shortest distance between each
      neighborhood center and the nearest clinic and having a clinic within 3 miles of
      each neighborhood center. RESULTS: The average 5-year non-age-adjusted rates were
      1,940 cases per 100,000 for Chlamydia and 60 per 100,000 for HPV-associated
      cancers. A large majority, 349 of 386 neighborhoods with high HPV-associated
      cancer rates and 532 of 537 neighborhoods with high Chlamydia rates, had a clinic
      within 3 miles of the neighborhood center. Clinics were more likely to be located
      within close proximity to high-risk neighborhoods in the inner city. High-risk
      neighborhoods outside of this urban core area were less likely to be near
      accessible clinics. CONCLUSIONS: The majority of high-risk neighborhoods were
      geographically near safety-net clinics with HPV vaccination services. Due to low
      rates of vaccination, these findings suggest that while services are
      geographically accessible, additional efforts are needed to improve uptake.
      Programs aimed to increase awareness about the vaccine and to link underserved
      groups to vaccination services are warranted.

PMID- 24043451
TI  - Multi-lineage potential research of bone marrow-derived stromal cells (BMSCs)
      from cattle.
AB  - Bovine bone marrow-derived mesenchymal stem cells (bBMSCs) were isolated from the
      bone marrow of a 4-6-month-old fetal bovine and then characterized by
      immunofluorescence and reverse transcriptase polymerase chain reaction. We found
      that primary bBMSCs could be expanded for 46 passages; the total culture time in
      vitro was 125 days. The results of surface antigen detection showed that bBMSCs
      expressed CD29, CD44, and CD73 but did not express endothelial cells and
      hematopoietic cells-specific marker CD31, CD34, and CD45. The cells from four
      passages (passages 3, 9, 15, and 25) were successfully induced to differentiate
      into osteoblasts, adipocytes, hepatic, and islet-like cells. The results indicate
      the potential for multi-lineage differentiation of bBMSCs that may represent an
      ideal candidate for cellular transplantation therapy.

PMID- 24043452
TI  - Bioproduction of food additives hexanal and hexanoic acid in a microreactor.
AB  - Hexanal and hexanoic acid have number of applications in food and cosmetic
      industry because of their organoleptic characteristics. Problems like low yields,
      formation of unwanted by-products, and large quantities of waste in their
      traditional production processes are the reasons for developing new production
      methods. Biotransformation in a microreactor, as an alternative to classical
      synthesis processes, is being investigated. Because conditions in microreactors
      can be precisely controlled, the quality of the product and its purity can also
      be improved. Biocatalytic oxidation of hexanol to hexanal and hexanoic acid using
      suspended and immobilized permeabilized whole baker's yeast cells and suspended
      and immobilized purified alcohol dehydrogenase (ADH) was investigated in this
      study. Three different methods for covalent immobilization of biocatalyst were
      analyzed, and the best method for biocatalyst attachment on microchannel wall was
      used in the production of hexanal and hexanoic acid. 

PMID- 24043453
TI  - Hepatoprotective effect of beta-chitosan from gladius of Sepioteuthis lessoniana
      against carbon tetrachloride-induced oxidative stress in Wistar rats.
AB  - Chitosan has attracted much attention as a biomedical material, owing to its
      unique biological activities. In this study, hepatoprotective effect of beta
      chitosan obtained from the gladius of squid Sepioteuthis lessoniana was studied
      against carbon tetrachloride (CCl4)-induced oxidative stress and liver injury in
      rats. The rats that received beta-chitosan along with the administration of CCl4
      showed significantly decreased plasma and tissue alanine aminotransferase (ALT)
      and aspartate aminotransferase (AST) activities and total cholesterol,
      triglyceride (TG) and free fatty acid (FFA) contents, whereas the treatment with
      beta-chitosan alone markedly increased rat hepatic and circulatory superoxide
      dismutase (SOD), catalase and glutathione peroxidase (GPx) and reduced
      glutathione (GSH) levels and decreased the malondialdehyde level.
      Histopathological observations recommended the marked hepatoprotective effect of
      beta-chitosan. The CCl4-induced alterations on circulatory and hepatic
      antioxidant defence system were normalised by beta-chitosan, and it could be
      concluded that the hepatoprotective effect of chitosan may be due to its
      antioxidant and antilipidemic property. Therefore, beta-chitosan could be
      considered as antihepatotoxic agent.

PMID- 24043454
TI  - Emulsifying, flocculating, and physicochemical properties of exopolysaccharide
      produced by cyanobacterium Nostoc flagelliforme.
AB  - The emulsifying, flocculating, and physicochemical properties of purified
      exopolysaccharide (EPS) of terrestrial cyanobacterium Nostoc flagelliforme
      cultured in liquid media were investigated. The EPS was defined as
      heteropolysaccharide composed by 41.2 % glucose, 21.1 % galactose, 21.0 %
      mannose, 2.5 % fructose, 3.6 % ribose, 1.7 % xylose, 0.6 % arabinose, 3.0 %
      rhamnose, 0.9 % fucose, and 4.3 % glucuronic acid. The EPS possessed higher
      intrinsic viscosity than other cyanobacterial strains as reported and displayed
      pseudoplastic behavior in aqueous solution. The EPS produced more stable
      emulsions with tested hydrocarbons and oils than xanthan gum, and the
      emulsification indexes with n-hexadecane, liquid paraffin, and peanut oil were
      higher than 50 %, indicating the strong emulsion-stabilizing capacity. The EPS
      showed peak flocculating rates of 93.5 and 86.1 % in kaolin and MgO suspension,
      respectively, and exhibited a better flocculation performance than Al2(SO4)3 and
      xanthan gum. These results demonstrated that the EPS of N. flagelliforme was a
      very promising candidate for numerous industrial applications, as it had higher
      intrinsic viscosity, good emulsification activity, and excellent flocculation
      capability.

PMID- 24043455
TI  - Miniaturized sequencing gel system for quick analysis of DNA by hydroxyl radical
      cleavage.
AB  - We described a simple and quick miniaturized sequencing gel system for DNA
      analysis. Two major modifications were made to the previously reported
      miniaturized DNA sequencing gel system to achieve high-resolution hydroxyl
      radical cleavage analysis: including formamide in the miniaturized gel and
      providing uniform heating during electrophoresis. Our method enables one to
      reduce the cost for chemicals and to significantly reduce electrophoresis time.
      Furthermore, minimal gel handling simplifies the entire process. We show that the
      resolution of DNA fragments obtained by hydroxyl radical cleavage for the
      miniaturized gel is similar to that of a large conventional sequencing gel.

PMID- 24043456
TI  - Inhaler competence and patient satisfaction with Easyhaler(r): results of two
      real-life multicentre studies in asthma and COPD.
AB  - OBJECTIVE: The aim of this study was to investigate patients' inhaler competence
      and satisfaction with the Easyhaler((r)) dry powder inhaler. DESIGN: Two open,
      uncontrolled, non-randomised studies. SETTING: Real life based on patients
      attending 56 respiratory clinics in Hungary. PARTICIPANTS: Patients with asthma
      or chronic obstructive pulmonary disease (COPD) (n = 1016). INTERVENTION: In a 3
      month study, adult patients (age range 18-88 years; n = 797) received twice-daily
      inhalations of formoterol via Easyhaler((r)), and in a consequential study (from
      one visit to another, with 3-12 months in-between) children and adolescents (age
      range 4-17 years; n = 219) received salbutamol via Easyhaler((r)) as needed. MAIN
      OUTCOME MEASURES: Control of six Easyhaler((r)) handling steps and patients'
      satisfaction with Easyhaler((r)) based on questionnaires. RESULTS: Correct
      performances (minimum and maximum of the six steps) were noticed after one
      demonstration in 92-98% of the adults, 87-99% of the elderly, 81-96% of the
      children and 83-99% of the adolescents. These figures had markedly increased at
      the last visit. Repeat instructions were necessary in 26% of the cases.
      Investigators found Easyhaler((r)) easy to teach in 87% of the patients and
      difficult in only 0.5%. Patients found Easyhaler((r)) easy to learn and use, and
      the patients' (and parents') satisfaction with the inhaler was very high. Lung
      function values [forced expiratory volume in 1 s (FEV1), forced vital capacity
      (FVC), peak expiratory flow (PEF)] improved statistically significantly during
      the studies, indicating good inhaler competence and treatment adherence.
      CONCLUSION: Investigators found Easyhaler((r)) easy to teach and patients found
      it easy to use, and their satisfaction with the device was high.

PMID- 24043457
TI  - Investigation of the hemostatic effect of a transdermal patch containing 0.55 mg
      ethinyl estradiol and 2.1 mg gestodene compared with a monophasic oral
      contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel: an
      open-label, randomized, crossover study.
AB  - BACKGROUND: Transdermal delivery of contraceptives offers several advantages over
      combined oral contraceptives (COCs), including effective absorption and the
      provision of relatively constant serum concentrations. Ethinyl estradiol (EE) and
      the progestin gestodene are well-absorbed through the skin and, therefore, well
      suited for use in a transdermal contraceptive patch. OBJECTIVE: The objective of
      this study was to investigate the impact of a once-weekly transparent,
      transdermal patch delivering low doses of EE and gestodene equivalent to a COC
      containing 0.02 mg EE and 0.06 mg gestodene on hemostasis parameters compared
      with a monophasic COC containing 0.03 mg EE and 0.15 mg levonorgestrel. METHODS:
      In this single-center, open-label, randomized, crossover study, 30 women (aged 18
      35 years) received three cycles of each treatment, separated by a two-cycle
      washout period. The primary outcome measure was the absolute change from baseline
      in prothrombin fragments 1 + 2 and D-dimer. RESULTS: For both treatments,
      prothrombin fragments 1 + 2 remained stable during the first treatment period,
      and increased only slightly in the second period (mean absolute change 0.025 and
      0.028 nmol/L in the novel Bayer patch and COC groups, respectively). Increases in
      D-dimer were observed in both periods (mean absolute change 107.0 +/- 147.2 ng/L
      for the novel Bayer patch and 113.7 +/- 159.0 ng/L for the COC). There were no
      statistically significant treatment differences in prothrombin 1 + 2 or D-dimer
      (p = 0.667 and p = 0.884, respectively) and no statistically significant
      treatment sequence or period effects. CONCLUSION: A COC containing 0.03 mg EE and
      0.15 mg levonorgestrel and the novel Bayer patch have comparable influence on
      hemostatic endpoints. Both treatments were well-tolerated by subjects.

PMID- 24043458
TI  - A simple model-free method for direct assessment of fluorescent ligand binding by
      linear spectral summation.
AB  - Fluorescent tagged ligands are commonly used to determine binding to proteins.
      However, bound and free ligand concentrations are not directly determined.
      Instead the response in a fluorescent ligand titration experiment is considered
      to be proportional to the extent of binding and, therefore, the maximum value of
      binding is scaled to the total protein concentration. Here, a simple model-free
      method is presented to be performed in two steps. In the first step, normalized
      bound and free spectra of the ligand are determined. In the second step, these
      spectra are used to fit composite spectra as the sum of individual components or
      linear spectral summation. Using linear spectral summation, free and bound 1
      Anilinonaphthalene-8-Sulfonic Acid (ANS) fluorescent ligand concentrations are
      directly calculated to determine ANS binding to tear lipocalin (TL), an
      archetypical ligand binding protein. Error analysis shows that the parameters
      that determine bound and free ligand concentrations were recovered with high
      certainty. The linear spectral summation method is feasible when fluorescence
      intensity is accompanied by a spectral shift upon protein binding. Computer
      simulations of the experiments of ANS binding to TL indicate that the method is
      feasible when the fluorescence spectral shift between bound and free forms of the
      ligand is just 8 nm. Ligands tagged with environmentally sensitive fluorescent
      dyes, e.g., dansyl chromophore, are particularly suitable for this method.

PMID- 24043459
TI  - Asymmetric synthesis of alpha-amino acids via homologation of Ni(II) complexes of
      glycine Schiff bases. Part 2: aldol, Mannich addition reactions, deracemization
      and (S) to (R) interconversion of alpha-amino acids.
AB  - This review provides a comprehensive treatment of literature data dealing with
      asymmetric synthesis of alpha-amino-beta-hydroxy and alpha,beta-diamino acids via
      homologation of chiral Ni(II) complexes of glycine Schiff bases using aldol and
      Mannich-type reactions. These reactions proceed with synthetically useful
      chemical yields and thermodynamically controlled stereoselectivity and allow
      direct introduction of two stereogenic centers in a single operation with
      predictable stereochemical outcome. Furthermore, new application of Ni(II)
      complexes of alpha-amino acids Schiff bases for deracemization of racemic alpha
      amino acids and (S) to (R) interconversion providing additional synthetic
      opportunities for preparation of enantiomerically pure alpha-amino acids, is also
      reviewed. Origin of observed diastereo-/enantioselectivity in the aldol, Mannich
      type and deracemization reactions, generality and limitations of these
      methodologies are critically discussed. 

PMID- 24043461
TI  - Bidirectional fluxes of spermine across the mitochondrial membrane.
AB  - The polyamine spermine is transported into the mitochondrial matrix by an
      electrophoretic mechanism having as driving force the negative electrical
      membrane potential (DeltaPsi). The presence of phosphate increases spermine
      uptake by reducing DeltapH and enhancing DeltaPsi. The transport system is a
      specific uniporter constituted by a protein channel exhibiting two asymmetric
      energy barriers with the spermine binding site located in the energy well between
      the two barriers. Although spermine transport is electrophoretic in origin, its
      accumulation does not follow the Nernst equation for the presence of an efflux
      pathway. Spermine efflux may be induced by different agents, such as FCCP,
      antimycin A and mersalyl, able to completely or partially reduce the DeltaPsi
      value and, consequently, suppress or weaken the force necessary to maintain
      spermine in the matrix. However this efflux may also take place in normal
      conditions when the electrophoretic accumulation of the polycationic polyamine
      induces a sufficient drop in DeltaPsi able to trigger the efflux pathway. The
      release of the polyamine is most probably electroneutral in origin and can take
      place in exchange with protons or in symport with phosphate anion. The activity
      of both the uptake and efflux pathways induces a continuous cycling of spermine
      across the mitochondrial membrane, the rate of which may be prominent in imposing
      the concentrations of spermine in the inner and outer compartment. Thus, this
      event has a significant role on mitochondrial permeability transition modulation
      and consequently on the triggering of intrinsic apoptosis. 

PMID- 24043460
TI  - Lysine metabolism in mammalian brain: an update on the importance of recent
      discoveries.
AB  - The lysine catabolism pathway differs in adult mammalian brain from that in
      extracerebral tissues. The saccharopine pathway is the predominant lysine
      degradative pathway in extracerebral tissues, whereas the pipecolate pathway
      predominates in adult brain. The two pathways converge at the level of ?(1)
      piperideine-6-carboxylate (P6C), which is in equilibrium with its open-chain
      aldehyde form, namely, alpha-aminoadipate delta-semialdehyde (AAS). A unique
      feature of the pipecolate pathway is the formation of the cyclic ketimine
      intermediate ?(1)-piperideine-2-carboxylate (P2C) and its reduced metabolite L
      pipecolate. A cerebral ketimine reductase (KR) has recently been identified that
      catalyzes the reduction of P2C to L-pipecolate. The discovery that this KR, which
      is capable of reducing not only P2C but also other cyclic imines, is identical to
      a previously well-described thyroid hormone-binding protein [MU-crystallin
      (CRYM)], may hold the key to understanding the biological relevance of the
      pipecolate pathway and its importance in the brain. The finding that the KR
      activity of CRYM is strongly inhibited by the thyroid hormone 3,5,3'
      triiodothyronine (T3) has far-reaching biomedical and clinical implications. The
      inter-relationship between tryptophan and lysine catabolic pathways is discussed
      in the context of shared degradative enzymes and also potential regulation by
      thyroid hormones. This review traces the discoveries of enzymes involved in
      lysine metabolism in mammalian brain. However, there still remain unanswered
      questions as regards the importance of the pipecolate pathway in normal or
      diseased brain, including the nature of the first step in the pathway and the
      relationship of the pipecolate pathway to the tryptophan degradation pathway. 

PMID- 24043462
TI  - CD39-mediated effect of human bone marrow-derived mesenchymal stem cells on the
      human Th17 cell function.
AB  - This study investigated the immune-modulatory effects of human bone marrow
      derived mesenchymal stem cells (hBMSCs) on human Th17 cell function through the
      CD39-mediated adenosine-producing pathway. The suppressive effects of hBMSCs were
      evaluated by assessing their effects on the proliferation of Th17 cells and the
      secretion of interferon (IFN)-gamma and interleukin (IL)-17A by Th17 cells with
      or without anti-CD39 treatment. Changes in CD39 and CD73 expression on the T
      cells with or without co-culture of hBMSCs were evaluated by flow cytometry.
      hBMSCs effectively suppressed the proliferation of Th17 cells and the secretion
      of both IL-17A and IFN-gamma from Th17 cells using by both flow cytometry and
      ELISA, while anti-CD39 treatment significantly reduced the inhibitory effects of
      hBMSCs on the proliferation and secretion of the Th17 cells. The hBMSCs induced
      increased expression of the CD39 and CD73 on T cells correlated with the
      suppressive function of hBMSCs, which was accompanied by increased adenosine
      production. Our data suggests that hBMSCs can effectively suppress immune
      responses of the Th17 cells via the CD39-CD73-mediated adenosine-producing
      pathway. 

PMID- 24043463
TI  - Lessons learned from radiation oncology clinical trials.
AB  - A workshop entitled "Lessons Learned from Radiation Oncology Trials" was held on
      December 7-8, 2011, in Bethesda, MD, to present and discuss some of the recently
      conducted radiation oncology clinical trials with a focus on those that failed to
      refute the null hypothesis. The objectives of this workshop were to summarize and
      examine the questions that these trials provoked, to assess the quality and
      limitations of the preclinical data that supported the hypotheses underlying
      these trials, and to consider possible solutions to these challenges for the
      design of future clinical trials. Several themes emerged from the discussions:
      (i) opportunities to learn from null-hypothesis trials through tissue and imaging
      studies; (ii) value of preclinical data supporting the design of combinatorial
      therapies; (iii) significance of validated biomarkers; (iv) necessity of quality
      assurance in radiotherapy delivery; (v) conduct of sufficiently powered studies
      to address the central hypotheses; and (vi) importance of publishing results of
      the trials regardless of the outcome. The fact that well-designed hypothesis
      driven clinical trials produce null or negative results is expected given the
      limitations of trial design and complexities of cancer biology. It is important
      to understand the reasons underlying such null results, however, to effectively
      merge the technologic innovations with the rapidly evolving biology for maximal
      patient benefit through the design of future clinical trials.

PMID- 24043464
TI  - Aflibercept and its role in the treatment of colorectal cancer--letter.

PMID- 24043467
TI  - The effects of flaxseed oil on cadmium-induced oxidative stress in rats.
AB  - In the present study, the effects of flaxseed oil on the oxidant-antioxidant
      system in cadmium intoxication were investigated in rats. Forty-eight male Wistar
      albino rats were divided into four equal groups (group 1). No treatment was
      applied to the control group. On the other hand, groups 2, 3, and 4 were
      administered with 0.1 ml/rat/day (~500 mg/kg bw) flaxseed oil by gavage into the
      stomach, 50 ppm of cadmium (~4 mg/kg bw) in ad libitum drinking water, and 0.1
      ml/rat/day flaxseed oil plus 50 ppm of cadmium, respectively, for 30 days. At the
      end of the study, malondialdehyde and nitric oxide levels and catalase,
      superoxide dismutase, and glutathione peroxidase activities were measured in
      blood and tissue (liver, lung, kidney, brain, heart, and testes) samples. While
      malondialdehyde and nitric oxide levels increased in the group given cadmium
      compared to the control group; in the meantime, there were some significant
      changes in antioxidant enzyme activities. These changes were observed, the trends
      of decrease or increase compared to the control group. There were positive
      changes in parameters of the group given with flaxseed oil plus cadmium compared
      to the group receiving cadmium alone, in other words, values were seen coming
      close to control group. As a result, cadmium exposure caused oxidative damage to
      erythrocytes and organs at varying rates, while flaxseed oil reduced the severity
      of cadmium-induced lipid peroxidation. Therefore, it was concluded that flaxseed
      oil can be used among compounds as a therapeutic agent or food additive for
      prophylaxis in cadmium intoxication. 

PMID- 24043468
TI  - Echocardiography in hypertension: practical recommendations from the Italian
      Society of Hypertension (SIIA).
AB  - In this document some indications on practical management of patients with
      arterial hypertension are discussed and recommendations for how, when and to whom
      perform an echocardiogram are given. 

PMID- 24043469
TI  - The crystal structure of an extracellular catechol oxidase from the ascomycete
      fungus Aspergillus oryzae.
AB  - Catechol oxidases (EC 1.10.3.1) catalyse the oxidation of o-diphenols to their
      corresponding o-quinones. These oxidases contain two copper ions (CuA and CuB)
      within the so-called coupled type 3 copper site as found in tyrosinases (EC
      1.14.18.1) and haemocyanins. The crystal structures of a limited number of
      bacterial and fungal tyrosinases and plant catechol oxidases have been solved. In
      this study, we present the first crystal structure of a fungal catechol oxidase
      from Aspergillus oryzae (AoCO4) at 2.5-A resolution. AoCO4 belongs to the newly
      discovered family of short-tyrosinases, which are distinct from other tyrosinases
      and catechol oxidases because of their lack of the conserved C-terminal domain
      and differences in the histidine pattern for CuA. The sequence identity of AoCO4
      with other structurally known enzymes is low (less than 30 %), and the crystal
      structure of AoCO4 diverges from that of enzymes belonging to the conventional
      tyrosinase family in several ways, particularly around the central alpha-helical
      core region. A diatomic oxygen moiety was identified as a bridging molecule
      between the two copper ions CuA and CuB separated by a distance of 4.2-4.3 A. The
      UV/vis absorption spectrum of AoCO4 exhibits a distinct maximum of absorbance at
      350 nm, which has been reported to be typical of the oxy form of type 3 copper
      enzymes. 

PMID- 24043470
TI  - Anticancer and immunostimulatory role of encapsulated tumor antigen containing
      cobalt oxide nanoparticles.
AB  - The purpose of this study is to evaluate the prospect of using surface modified
      cobalt oxide(CoO) nanoparticles as carriers of cancerantigens to human
      macrophages. N-Phosnomethyliminodiacetic acid (PMIDA) was used for surface
      modification to overcome the toxic effect of CoO nanoparticles. Here, the
      phosphonate group of the PMIDA acts as a surface-anchoring agent and the
      remaining -COOH groups bind nonspecifically with tumor associated antigens. This
      modification allows the conjugation of human oral carcinoma (KB) cell lysate (CL)
      as an antigen with PMIDA coated CoO nanoparticles (CL-PMIDA-CoO). Particle
      characterization was performed by dynamic light scattering, atomic force
      microscopy, and scanning electron microscopy studies. Fourier transform IR
      spectroscopy was used to investigate conjugation of the protein with
      nanoparticles. Protein encapsulation was confirmed by protein gel
      electrophoresis. Active uptake of antigen-conjugated nanoparticles by macrophages
      was confirmed by fluorescence microscopy. The antitumor activity of the
      nanocomplex pulsed macrophages was investigated on a human oral carcinoma cell
      line (KB) in vitro. The modified nanocomplexes upregulate IFN-gamma and TNF-alpha
      and induce an anticancer immune response by activating macrophages. The use of
      TNF-alpha inhibitor confirmed the ability of the CL-PMIDA-CoO nanocomplex to
      stimulate TNF-alpha mediated immunostimulation. CL-PMIDA-CoO nanoparticles
      efficiently increased the CD4(+) population. Thus, our findings provide insight
      into the use of PMIDA coated CoO nanoparticles as antigen delivery vehicles. 

PMID- 24043471
TI  - Species-specific activation of Cu/Zn SOD by its CCS copper chaperone in the
      pathogenic yeast Candida albicans.
AB  - Candida albicans is a pathogenic yeast of important public health relevance.
      Virulence of C. albicans requires a copper and zinc containing superoxide
      dismutase (SOD1), but the biology of C. albicans SOD1 is poorly understood. To
      this end, C. albicans SOD1 activation was examined in baker's yeast
      (Saccharomyces cerevisiae), a eukaryotic expression system that has proven
      fruitful for the study of SOD1 enzymes from invertebrates, plants, and mammals.
      In spite of the 80% similarity between S. cerevisiae and C. albicans SOD1
      molecules, C. albicans SOD1 is not active in S. cerevisiae. The SOD1 appears
      incapable of productive interactions with the copper chaperone for SOD1 (CCS1) of
      S. cerevisiae. C. albicans SOD1 contains a proline at position 144 predicted to
      dictate dependence on CCS1. By mutation of this proline, C. albicans SOD1 gained
      activity in S. cerevisiae, and this activity was independent of CCS1. We
      identified a putative CCS1 gene in C. albicans and created heterozygous and
      homozygous gene deletions at this locus. Loss of CCS1 resulted in loss of SOD1
      activity, consistent with its role as a copper chaperone. C. albicans CCS1 also
      restored activity to C. albicans SOD1 expressed in S. cerevisiae. C. albicans
      CCS1 is well adapted for activating its partner SOD1 from C. albicans, but not
      SOD1 from S. cerevisiae. In spite of the high degree of homology between the SOD1
      and CCS1 molecules in these two fungal species, there exists a species-specific
      barrier in CCS-SOD interactions which may reflect the vastly different lifestyles
      of the pathogenic versus the noninfectious yeast.

PMID- 24043472
TI  - Enhanced tissue regeneration potential of juvenile articular cartilage.
AB  - BACKGROUND: Articular cartilage undergoes substantial age-related changes in
      molecular composition, matrix structure, and mechanical properties. These age
      related differences between juvenile and adult cartilage manifest themselves as
      markedly distinct potentials for tissue repair and regeneration. PURPOSE: To
      compare the biological properties and tissue regeneration capabilities of
      juvenile and adult bovine articular cartilage. STUDY DESIGN: Controlled
      laboratory study. METHODS: Articular cartilage harvested from juvenile (age, 4
      months) and adult (age, 6-8 years) bovine femoral condyles was cultured for 4
      weeks to monitor chondrocyte migration, glycosaminoglycan content conservation,
      and new tissue formation. The cartilage cell density and proliferative activity
      were also compared. Additionally, the effects of age-related changes on cartilage
      gene expression were analyzed using the Affymetrix GeneChip array. RESULTS:
      Compared with adult cartilage, juvenile bovine cartilage demonstrated a
      significantly greater cell density, higher cell proliferation rate, increased
      cell outgrowth, elevated glycosaminoglycan content, and enhanced matrix
      metallopeptidase 2 activity. During 4 weeks in culture, only juvenile cartilage
      was able to generate new cartilaginous tissues, which exhibited pronounced
      labeling for proteoglycan and type II collagen but not type I collagen. With over
      19,000 genes analyzed, distinctive gene expression profiles were identified. The
      genes mostly involved in cartilage growth and expansion, such as COL2A1, COL9A1,
      MMP2, MMP14, and TGFB3, were upregulated in juvenile cartilage, whereas the genes
      primarily responsible for structural integrity, such as COMP, FN1, TIMP2, TIMP3,
      and BMP2, were upregulated in adult cartilage. CONCLUSION: As the first
      comprehensive comparison between juvenile and adult bovine articular cartilage at
      the tissue, cellular, and molecular levels, the results strongly suggest that
      juvenile cartilage possesses superior chondrogenic activity and enhanced
      regenerative potential over its adult counterpart. Additionally, the differential
      gene expression profiles of juvenile and adult cartilage suggest possible
      mechanisms underlying cartilage age-related changes in their regeneration
      capabilities, structural components, and biological properties. CLINICAL
      RELEVANCE: The results of this comparative study between juvenile and adult
      bovine articular cartilage suggest an enhanced regenerative potential of juvenile
      cartilage tissue in the restoration of damaged articular cartilage.

PMID- 24043473
TI  - Use of the Corus(r) CAD Gene Expression Test for Assessment of Obstructive
      Coronary Artery Disease Likelihood in Symptomatic Non-Diabetic Patients.
AB  - The determination of the underlying etiology of symptoms suggestive of
      obstructive coronary artery disease (CAD, >=50% stenosis in a major coronary
      artery) is a common clinical challenge in both primary care and cardiology
      clinics. Usual care in low to medium risk patients often involves a family
      history, risk factor assessment, and then stress testing with or without non
      invasive imaging. If positive, this is often followed by invasive coronary
      angiography (ICA). Despite extensive adoption of this usual care paradigm, more
      than 60% of patients referred for angiography do not have obstructive CAD. In
      order to robustly identify those symptomatic patients without obstructive CAD,
      who can avoid subsequent cardiac testing and look elsewhere for the cause of
      their symptoms, a recently described whole blood gene expression score (GES:
      Corus(r) CAD, CardioDx, Inc., Palo Alto, CA) has been developed and validated in
      two multi-center trials. This paper reviews the published literature and
      assessments by independent parties regarding the analytical and clinical validity
      as well as the clinical utility of the Corus(r) CAD test. 

PMID- 24043474
TI  - Current evidence for thoracic aorta type B dissection management.
AB  - Aortic dissection is a devastating cardiovascular condition and represents the
      most common aortic emergency. Outcome is determined by the type and extent of
      dissection and the presence of associated complications requiring early diagnosis
      and treatment. Aortic dissection is defined as acute within 14 days from onset
      and chronic after that time period. The natural course of type B dissection is
      determined by 2 elements, early and chronic complications. An uncomplicated acute
      type B dissection is less frequently lethal but it is not totally benign. Some
      peculiar issues must be taken into account, such as the high probability of
      complications development in a dissected aorta and the poor long-term prognosis
      on medical treatment alone. Then, it would be helpful to identify which patients
      with uncomplicated type B dissection will have a poorest aortic prognosis over
      time in order to apply an early intervention. 

PMID- 24043475
TI  - In situ revascularisation for femoropopliteal graft infection: ten years of
      experience with silver grafts.
AB  - PURPOSE: The purpose of this study was to analyze clinical outcome of patients
      for femoropopliteal graft infection who were treated by in situ reconstruction
      with a silver-coated prosthesis. BASIC METHODS: From December 2001 to December
      2011, 27 patients were treated for femoropopliteal graft infection. Twenty
      patients (74%) were male and seven (26%) were female. Mean age was 65 years. The
      primary endpoint was recurrence of infection. Secondary endpoints were early and
      late mortality and morbidity, primary graft patency, major amputation rates and
      patient survival. PRINCIPAL FINDINGS: Early reinfection occurred in 11% and late
      in 8% of patients. Perioperative mortality was 7% and late was 4%. Above-knee
      amputation was performed in 4% of patients during early postoperative course and
      in 12% of patients during follow-up. Early and late graft patency was 96% and
      72%, respectively. CONCLUSIONS: Results of in situ implantation of silver-coated
      grafts for femoropopliteal prosthesis infection are according to our opinion
      acceptable, but the risk of reinfection remains.

PMID- 24043476
TI  - Package of care for active management in labour for reducing caesarean section
      rates in low-risk women.
AB  - BACKGROUND: Approximately 15% of women have caesarean sections (CS) and while the
      rate varies, the number is increasing in many countries. This is of concern
      because higher CS rates do not confer additional health gain but may adversely
      affect maternal health and have implications for future pregnancies. Active
      management of labour has been proposed as a means of reducing CS rates. This
      refers to a package of care including strict diagnosis of labour, routine
      amniotomy, oxytocin for slow progress and one-to-one support in labour.
      OBJECTIVES: To determine whether active management of labour reduces CS rates in
      low-risk women and improves satisfaction. SEARCH METHODS: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (16 April 2013).
      SELECTION CRITERIA: Randomised controlled trials comparing low-risk women
      receiving a predefined package of care (active management) with women receiving
      routine (variable) care. Trials where slow progress had been diagnosed before
      entry into the trial were excluded. DATA COLLECTION AND ANALYSIS: At least two
      review authors extracted data. We assessed included studies for risk of bias.
      MAIN RESULTS: We included seven trials, with a total of 5390 women. The quality
      of studies was mixed. The CS rate was slightly lower in the active management
      group compared with the group that received routine care, but this difference did
      not reach statistical significance (RR 0.88, 95% CI 0.77 to 1.01). However, in
      one study there was a large number of post-randomisation exclusions. On excluding
      this study, CS rates in the active management group were statistically
      significantly lower than in the routine care group (RR 0.77 95% CI 0.63 to 0.94).
      More women in the active management group had labours lasting less than 12 hours,
      but there was wide variation in length of labour within and between trials. There
      were no differences between groups in use of analgesia, rates of assisted vaginal
      deliveries or maternal or neonatal complications. Only one trial examined
      maternal satisfaction; the majority of women (over 75%) in both groups were very
      satisfied with care. AUTHORS' CONCLUSIONS: Active management is associated with
      small reductions in the CS rate, but it is highly prescriptive and
      interventional. It is possible that some components of the active management
      package are more effective than others. Further work is required to determine the
      acceptability of active management to women in labour.

PMID- 24043478
TI  - Abstracts of the Neurocritical Care Society 11th Annual Meeting. October 1-4,
      2013. Philadelphia, Pennsylvania, USA.

PMID- 24043477
TI  - The prognostic value of a new tissue Doppler parameter in patients with heart
      failure.
AB  - It has been shown a good accuracy to predict high left ventricular end-diastolic
      pressure for a value >1.6 of a new tissue Doppler index, E/(E' * S'), including
      the ratio between early diastolic transmitral and mitral annulus velocity (E/E'),
      and the systolic mitral annulus velocity (S'). Our aim was to evaluate the
      prognostic value of E/(E' * S') > 1.6 in patients with heart failure (HF).
      Echocardiography was performed in 345 consecutive hospitalized patients with HF,
      in sinus rhythm, at hospital discharge and after 1 month. Worsening of E/(E' *
      S') was defined as any increase of baseline value. The primary end point
      consisted of cardiac death or readmission due to HF worsening in long term follow
      up. At discharge, 153 patients (44.3%) presented E/(E' * S') <= 1.6 (group I)
      while 192 patients (55.7%) presented E/(E' * S') > 1.6 (group II). During the
      follow-up period (35.1 +/- 8.7 months) the first cardiac event was cardiac death
      in 11 patients (3.1%) and readmission for HF in 179 patients (51.9%). The
      composite end point was significantly higher in group II than in group I (163
      events, 84.9 % vs. 27 events, 17.6%, p < 0.001). By multivariate Cox regression
      analysis, E/(E' * S') > 1.6 was the best independent predictor of cardiac events
      (hazard ratio = 4.46, 95% CI = 2.44-8.13, p = 0.001). Patients with E/(E' * S') >
      1.6 at discharge and its worsening after 1 month have presented the worst
      prognosis (all p < 0.05). In patients with HF, E/(E' * S') > 1.6 at hospital
      discharge is a powerful predictor of clinical outcome particularly if it is
      associated with worsening.

PMID- 24043479
TI  - Prolonged elevated heart rate is a risk factor for adverse cardiac events and
      poor outcome after subarachnoid hemorrhage.
AB  - INTRODUCTION: Sympathetic nervous system hyperactivity is common after
      subarachnoid hemorrhage (SAH). We sought to determine whether uncontrolled
      prolonged heart rate elevation is a risk factor for adverse cardiopulmonary
      events and poor outcome after SAH. METHODS: We prospectively studied 447 SAH
      patients between March 2006 and April 2012. Prior studies define prolonged
      elevated heart rate (PEHR) as heart rate >95 beats/min for >12 h. Major adverse
      cardiopulmonary events were documented according to the predefined criteria.
      Global outcome at 3 months was assessed with the modified Rankin Scale (mRS).
      RESULTS: 175 (39 %) patients experienced PEHR. Nonwhite race/ethnicity, admission
      Hunt-Hess grade >=4, elevated APACHE-2 physiological subscore, and modified
      Fisher score were significant admission predictors of PEHR, whereas documented
      pre-hospital beta-blocker use was protective. After controlling for admission
      Hunt-Hess grade, Cox regression using time-lagged covariates revealed that PEHR
      onset in the previous 48 h was associated with an increased hazard for delayed
      cerebral ischemia, myocardial injury, and pulmonary edema. PEHR was associated
      with 3-month poor outcome (mRS 4-6) after controlling for known predictors.
      CONCLUSIONS: PEHR is associated with major adverse cardiopulmonary events and
      poor outcome after SAH. Further study is warranted to determine if early
      sympatholytic therapy targeted at sustained heart rate control can improve
      outcome after SAH.

PMID- 24043480
TI  - Comparing sugary drinks in the food retail environment in six NYC neighborhoods.
AB  - Obesity is a national public health concern linked to numerous chronic health
      conditions among Americans of all age groups. Evidence suggests that
      discretionary calories from sugary drink consumption have been a significant
      contributor to excess caloric intake among both children and adults. Research has
      established strong links between retail food environments and purchasing habits
      of consumers, but little information exists on the sugary drink retail
      environment in urban neighborhoods. The objective of this assessment was to
      compare various aspects of the sugary drink retail environment across New York
      City (NYC) neighborhoods with disparate self-reported sugary drink consumption
      patterns. In-store retail audits were conducted at 883 corner stores, chain
      pharmacies, and grocery stores in 12 zip codes throughout NYC. Results showed
      that among all beverage types assessed, sugary drinks had the most prominent
      presence in the retail environment overall, which was even more pronounced in
      higher-consumption neighborhoods. In higher- versus lower-consumption
      neighborhoods, the mean number of sugary drink varieties available at stores was
      higher (11.4 vs. 10.4 varieties), stores were more likely to feature sugary drink
      advertising (97 vs. 89 %) and advertising at multiple places throughout the store
      (78 vs. 57 %), and several sugary drinks, including 20-oz Coke(r) or Pepsi(r),
      were less expensive ($1.38 vs. $1.60). These results, all statistically
      significant, indicate that neighborhoods characterized by higher levels of sugary
      drink consumption expose shoppers to sugary drinks to a greater extent than lower
      consumption neighborhoods. This builds upon evidence documenting the association
      between the environment and individual behavior.

PMID- 24043481
TI  - Celecoxib as a pre-emptive analgesia after arthroscopic knee surgery; a triple
      blinded randomized controlled trial.
AB  - BACKGROUND: Pre-emptive analgesia not only controls pain but also may result in
      the reduction of opioid consumption and related side effects following orthopedic
      surgeries. The purpose of the present study was to examine the therapeutic
      effects of celecoxib in reducing pain following the arthroscopic knee surgeries:
      anterior cruciate ligament (ACL) reconstruction and partial meniscectomy.
      MATERIALS AND METHODS: In this triple-blinded, randomized, placebo-controlled
      clinical trial, celecoxib 400 mg and identical placebo were administered, 2 h
      prior to operation, to 130 patient candidates for undergoing knee arthroscopic
      surgery of either isolated meniscectomy or ACL reconstruction. Pain intensity, 24
      h opioid consumption and the related side effects were measured at 6 and 24 h
      post operation. RESULTS: The patients in both groups were similar with regards to
      demographic characteristics such as age, gender and body mass index. The results
      of the study indicated that the pain intensity and opioid consumption were lower
      in both subgroups (meniscectomy and ACL-R) in celecoxib group at 6 and 24 h post
      operation (P < 0.0001). The side effects of analgesics such as nausea and
      vomiting, sedation, and dizziness were not significantly different between the
      two groups (P > 0.05). CONCLUSION: It seems that celecoxib as a pre-emptive
      analgesia agent is effective in decreasing acute postoperative pain and 24 h
      opioid consumption in patients undergoing arthroscopic knee surgery.

PMID- 24043482
TI  - A randomized clinical trial on the use of medical Portland cement, MTA and
      calcium hydroxide in indirect pulp treatment.
AB  - OBJECTIVES: Studies on indirect pulp treatment (IPT) show varying success rates
      of 73 to 97 %. The necessity of re-opening the cavity and the question of the
      optimal capping material is still under debate. The aim of this prospective in
      vivo study was to compare the clinical and microbiological outcomes of mineral
      trioxide aggregate (MTA), medical Portland cement, and calcium hydroxide on the
      dentin-pulp complex of permanent and primary teeth treated with two-step IPT.
      MATERIALS AND METHODS: In 86 regular patients (51 % men; 49 % women; age 17.2
      years +/-13.8), one deep carious lesion each was treated with incomplete caries
      removal, randomly selected capping with either calcium hydroxide (n = 31),
      medical Portland cement (29) or white MTA (26), and re-entry (6.3 months +/-1.0).
      Clinical (color, humidity, and consistency of dentin) and microbiological
      (Lactobacilli/Mutans Strep. counts) parameters were recorded at the first and
      second treatment. RESULTS: The IPT had a high success rate of 90.3 % regardless
      of the material used (p = 0.72). The arrested lesions showed consistently darker,
      dry, and therefore, sclerotic dentine (p < 0.05) as well as a decrease in
      bacterial counts at re-entry (Lactobacilli p = 0.01/Mutans Strep. p = 0.07).
      CONCLUSIONS: The findings of this study support the use of the IPT as a treatment
      for deep carious lesions preferably with non-resorbing materials such as MTA or
      medical Portland cement. CLINICAL RELEVANCE: The findings of this study could
      promote the improvement of the IPT as a one-step treatment of deep carious
      lesions when the remaining demineralized dentin would be sealed with durable
      restorations.

PMID- 24043483
TI  - Local repair of a trans-stomal ileocecal prolapse by stapler device.
AB  - The creation of a stoma, although considered a simple surgical procedure, is
      burdened by various complications, one of the most common being prolapse. Usually
      prolapse increases gradually, involving generally limited functional disorders
      and it can be well managed with non-operative measures. Occasionally it requires
      major surgery, for severe skin excoriation, bleeding or incarceration of the
      bowel. However, for critical clinical conditions of patients, often is not
      possible to use classical techniques, as bowel-pexy fixation or resection of the
      prolapse. Maeda has described a simple method for the correction of prolapse of
      the transverse colon using a stapler device that can be applied in this type of
      patients. In this report, we describe the first application of this technique to
      treat the prolapse of the ileocecal loop in an 81-year old woman, suffering from
      Parkinson's disease. A definitive ciecum stoma was performed the previous year
      for an Olgivie syndrome. At 6 months, follow-up showed no recurrence of prolapse
      with a functional stoma and without any skin irritation. In conclusion, this
      approach is recommended especially for high-risk patients who cannot be submitted
      to a much more invasive treatment. In fact, the main advantages consist of a
      minimally invasive technique, with minimal blood loss and with a rapid recovery
      of a normal quality of life.

PMID- 24043484
TI  - Obstructive sleep apnea: no independent association to troponins.
AB  - BACKGROUND: Cardiac troponins (cTn) are to date the most sensitive and specific
      biochemical markers of myocardial injury. Abnormal breathing patterns in patients
      with obstructive sleep apnea (OSA) may cause myocardial cell stress detectable by
      novel cTn assays. The objectives of this study were to investigate whether a new
      single-molecule cTnI (S-cTnI) assay and a commercially available high-sensitivity
      cTnT (hs-cTnT) assay would detect myocyte injury in individuals evaluated for
      possible OSA, and to explore their relation to variables of disordered breathing
      during sleep. METHODS: Consecutive individuals referred to Lovisenberg Diakonale
      Hospital's sleep laboratory between 1 October 2009 and 1 March 2010 were
      included. We measured cTn in specimens collected the morning after sleep and
      studied these in relation to variables recorded during polygraphy or
      polysomnography. RESULTS: All 222 (100 %) individuals had measurable cTn levels
      using either assay. Stratified into categories according to the apnea-hypopnea
      index (AHI), patients with OSA (AHI >=5) had a different distribution of S-cTnI
      (P = 0.036) and hs-cTnT (P = 0.002) compared to those without (AHI <5). The
      median (quartiles 1-3) were 3.0 (1.9-6.0) versus 2.3 (1.6-3.8) ng/l for S-cTnI,
      and 7.0 (5.5-8.7) versus 6.2 (4.9-7.2) ng/l for hs-cTnT. However, in multiple
      median regression analyses adjusted for conventional predictors, neither S-cTnI
      (P = 0.57) nor hs-cTnT (P = 0.80) were significantly associated with AHI.
      CONCLUSIONS: This study reveals no association independent of conventional
      predictors between OSA and myocardial cell injury measured by S-cTnI and hs-cTnT
      assays. Our findings support a search for novel biomarkers for prognostication of
      OSA.

PMID- 24043485
TI  - Prevalence of obstructive sleep apnea syndrome in Japanese elementary school
      children aged 6-8 years.
AB  - PURPOSE: We aimed to determine the prevalence of and the risk factors for
      obstructive sleep apnea syndrome (OSAS) in Japanese children aged 6-8 years.
      METHODS: The parents of 202 children aged 6-8 years who attended a single
      elementary school in Shiga, Japan, were requested to complete the Child and
      Adolescent Sleep Checklist (CASC) and perform home Type 3 portable monitoring of
      their children. By using the CASC data and monitor recordings, we estimated the
      prevalence of pediatric OSAS with the help of different diagnostic criteria and
      identified the risk factors associated with OSAS. RESULTS: Complete data were
      obtained from 170 of the 194 children whose parents participated in the study.
      The mean total apnea-hypopnea index and obstructive apnea hypopnea index were 1.4
      +/- 1.3 and 0.4 +/- 0.6 h(-1), respectively, and central apnea was the most
      prevalent type of respiratory event, accounting for 70.4% of all events. The
      overall prevalence of OSAS ranged from 0.6% to 43.5%, depending on the cutoff
      value used, and was 3.5% when using International Criteria of Sleep Disorders
      version II (ICSD II) diagnostic criteria. The presence of tonsillar hypertrophy
      was the only parameter whose prevalence was significantly elevated in children
      with OSAS across all diagnostic criteria. CONCLUSIONS: The prevalence of
      pediatric OSAS varies according to the diagnostic criteria used, indicating the
      need for further research focusing on outcomes to define a clinically significant
      diagnostic threshold. The presence of tonsillar hypertrophy is an important risk
      factor in the development of pediatric OSAS.

PMID- 24043486
TI  - Communicating with employers: experiences of occupational therapists treating
      people with musculoskeletal conditions.
AB  - PURPOSE: Many employed people with musculoskeletal conditions rely on healthcare
      practitioners, including occupational therapists, for work-related advice and
      support. Good communication between healthcare practitioners and employers is
      considered vital in facilitating work retention and return to work. The purpose
      of this study was to explore the experiences of occupational therapists in
      communicating with patients' employers. METHODS: Qualitative data were collected
      from the responses of occupational therapists to ten statements/open questions in
      a questionnaire survey of UK occupational therapists. Data were copied verbatim
      into word documents and analysed thematically. RESULTS: A total of 649 comments
      were made by 143 respondents. Five themes were identified that were associated
      with communicating with employers: patient-dependent; employer-dependent;
      therapist-dependent; extrinsic factors; methods of communication. CONCLUSION:
      This study has identified that communication between occupational therapists and
      employers is influenced by a number of factors, including those which are outside
      the therapists' control. These need to be acknowledged and addressed by
      therapists, their professional organisation, employers, commissioners, therapy
      service managers, educators and employees in order to support return-to-work and
      work retention of people with musculoskeletal conditions.

PMID- 24043487
TI  - Adverse reactions to targeted and non-targeted chemotherapeutic drugs with
      emphasis on hypersensitivity responses and the invasive metastatic switch.
AB  - More than 100 drugs are used to treat the many different cancers. They can be
      divided into agents with relatively broad, non-targeted specificity and targeted
      drugs developed on the basis of a more refined understanding of individual
      cancers and directed at specific molecular targets on different cancer cells.
      Individual drugs in both groups have been classified on the basis of their
      mechanism of action in killing cancer cells. The targeted drugs include
      proteasome inhibitors, toxic chimeric proteins and signal transduction inhibitors
      such as tyrosine kinase (non-receptor and receptor), serine/threonine kinase,
      histone deacetylase and mammalian target of rapamycin inhibitors. Increasingly
      used targeted vascular (VEGF) and platelet-derived endothelial growth factor
      blockade can provoke a range of pathological consequences. Many of the non
      targeted drugs are cytotoxic, suppressing haematopoiesis as well as provoking
      cutaneous eruptions and vascular, lung and liver injury. Cytotoxic side effects
      of the targeted drugs occur less often and usually with less severity, but they
      show their own unusual adverse effects including, for example, a lengthened QT
      interval, a characteristic papulopustular rash, nail disorders and a hand-foot
      skin reaction variant. The term hypersensitivity is widely used across a number
      of disciplines but not always with the same definition in mind, and the
      terminology needs to be standardised. This is particularly apparent in cancer
      chemotherapy where anti-neoplastic drug-induced thrombocytopenia, neutropenia,
      anaemia, vascular disorders, liver injury and lung disease as well as many
      dermatological manifestations sometimes have an immune basis. The most insidious
      of all adverse consequences of targeted therapies, however, are tumour
      adaptation, increased malignancy and the invasive metastatic switch seen with
      anti-angiogenic drugs that inhibit the VEGF-A pathway. Adverse reactions to 44
      non-targeted and 33 targeted, frequently used, chemotherapeutic drugs are
      presented together with discussions of diagnosis, premedications,
      desensitizations and importance of understanding the mechanisms underlying the
      various drug-induced reactions. There is need for wide-ranging acceptance of what
      constitutes a hypersensitivity reaction and for allergists to be more involved in
      the diagnosis, treatment and prevention of chemotherapeutic drug-induced
      hypersensitivity reactions. 

PMID- 24043488
TI  - Endovascular coil embolization of a costocervical trunk pseudoaneurysm after
      bullectomy with pleural abrasion.
AB  - Transarterial embolization (TAE) is less invasive than surgery for the treatment
      of pseudoaneurysms. Costocervical trunk (CCT) pseudoaneurysms are extremely rare.
      We herein report an unusual case of a 45-year-old man with a CCT pseudoaneurysm
      caused by a bullectomy with pleural abrasion, which had been performed to manage
      a spontaneous pneumothorax. The patient presented with chronic chest pain and
      successfully underwent TAE with a metallic coil. The chest pain completely
      disappeared 2 weeks after the TAE, and follow-up computed tomography showed that
      the pseudoaneurysm had almost completely disappeared 9 months after the TAE. 

PMID- 24043489
TI  - Functional characterization of a porcine emphysema model.
AB  - BACKGROUND: Lung emphysema is a central feature of chronic obstructive pulmonary
      disease (COPD), a frequent human disease worldwide. Cigarette smoking is the
      major cause of COPD, but genetic predisposition seems to be an important factor.
      Mutations in surfactant protein genes have been linked to COPD phenotypes in
      humans. Also, the catalytic activities of metalloproteinases (MMPs) are central
      in the pathogenesis of emphysema/COPD. Especially MMP9, but also MMP2, MMP7, and
      MMP12 seem to be involved in human emphysema. MMP12-/- mice are protected from
      smoke-induced emphysema. ITGB6-/- mice spontaneously develop age-related lung
      emphysema due to lack of ITGB6-TGF-beta1 regulation of the MMP12 expression.
      METHODS: A mutated pig phenotype characterized by age-related lung emphysema and
      resembling the ITGB6-/- mouse has been described previously. To investigate the
      emphysema pathogenesis in this pig model, we examined the expression of MMP2,
      MMP7, MMP9, MMP12, and TGF-beta1 by quantitative PCR (qPCR). In addition,
      immunohistochemical stainings of the lungs with SP-B, SP-C, MMP9, and MMP12
      antibodies were performed. The haematologic/immunologic status of the pigs also
      was studied. RESULTS: The qPCR study showed no difference between pigs with and
      without emphysema, and no systemic differences were indicated by the haematologic
      and immunologic studies. However, the immunohistochemical stainings showed an
      increased expression of MMP9 and MMP12 in older, mutated pigs (with emphysema)
      compared with normal and young mutated pigs (without emphysema). CONCLUSIONS: The
      pig model is comparable to human emphysema patients and the ITGB6-/- mouse model
      with respect to both morphology and functionality.

PMID- 24043491
TI  - Point: new trichs for "old" dogs: prospects for expansion of Trichomonas
      vaginalis screening.

PMID- 24043490
TI  - Fungal infection mimicking pulmonary malignancy: clinical and radiological
      characteristics.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical and
      radiological features of patients with fungal infection mimicking thoracic
      malignancy and to establish a diagnostic approach for both clinicians and
      radiologists to avoid misdiagnosis. METHODS: In this retrospective study, we
      reviewed clinical and computed tomography (CT) findings from 27 patients who
      presented with suspicion of thoracic malignancy who were ultimately diagnosed
      with fungal disease. RESULTS: Patients' median age was 55.7 (range 31-78) years.
      The most common clinical findings were cough (48.1 %), expectoration (33.3 %),
      chest pain (25.9 %), weakness (25.9 %), weight loss (18.5 %), and hemoptysis,
      dyspnea, and fever (7.4 % each). The median lesion size was 35.5 (range 10-85)
      mm. CT findings included a solid nodule (51.9 %), solid mass (37 %), or both
      (11.1 %). Nodule and mass margins were lobulated in 9 (33.3 %) patients, ill
      defined in 5 (18.5 %), spiculated in 4 (14.8 %), and smooth in 4 (14.8 %)
      patients. Additional findings included consolidation in 4 (14.8 %) patients,
      cavitation in 3 (11.1 %), pleural effusion in 2 (7.4 %), and lymphadenopathy in
      11 (40.7 %) patients. In all patients, specific diagnoses were made and confirmed
      by histopathology; final diagnoses were histoplasmosis (25.9 %), coccidiomycosis
      (22.2 %), cryptococcosis (22.2 %), aspergillosis (14.8 %), North American
      blastomycosis (7.4 %), mucormycosis (3.75 %), and paracoccidioidomycosis (3.75
      %). CONCLUSIONS: Fungal infection can present with clinical and radiological
      features that are indistinguishable from thoracic malignancy, such as lung
      nodules or masses. Because the management and outcomes of fungal infection and
      malignancy are entirely distinct, the establishment of a specific diagnosis is
      critical to provide appropriate therapy.

PMID- 24043492
TI  - Counterpoint: screening for Trichomoniasis--where's the evidence of benefit?

PMID- 24043493
TI  - Retooling the pap smear for ovarian and endometrial cancer detection.

PMID- 24043494
TI  - Week-to-week biological variation in the N-terminal prohormone of brain
      natriuretic peptide in hemodialysis patients and healthy individuals.

PMID- 24043495
TI  - Gibberellin mediates the development of gelatinous fibres in the tension wood of
      inclined Acacia mangium seedlings.
AB  - BACKGROUND AND AIMS: Gibberellin stimulates negative gravitropism and the
      formation of tension wood in tilted Acacia mangium seedlings, while inhibitors of
      gibberellin synthesis strongly inhibit the return to vertical growth and suppress
      the formation of tension wood. To characterize the role of gibberellin in tension
      wood formation and gravitropism, this study investigated the role of gibberellin
      in the development of gelatinous fibres and in the changes in anatomical
      characteristics of woody elements in Acacia mangium seedlings exposed to a
      gravitational stimulus. METHODS: Gibberellin, paclobutrazol and uniconazole-P
      were applied to the soil in which seedlings were growing, using distilled water
      as the control. Three days after the start of treatment, seedlings were inclined
      at 45  degrees  to the vertical and samples were harvested 2 months later. The
      effects of the treatments on wood fibres, vessel elements and ray parenchyma
      cells were analysed in tension wood in the upper part of inclined stems and in
      the opposite wood on the lower side of inclined stems. KEY RESULTS: Application
      of paclobutrazol or uniconazole-P inhibited the increase in the thickness of
      gelatinous layers and prevented the elongation of gelatinous fibres in the
      tension wood of inclined stems. By contrast, gibberellin stimulated the
      elongation of these fibres. Application of gibberellin and inhibitors of
      gibberellin biosynthesis had only minor effects on the anatomical characteristics
      of vessel and ray parenchyma cells. CONCLUSIONS: The results suggest that
      gibberellin is important for the development of gelatinous fibres in the tension
      wood of A. mangium seedlings and therefore in gravitropism.

PMID- 24043496
TI  - Overexpression of nuclear beta-catenin at invasive front in rectal carcinoma is
      associated with lymph node metastasis and poor prognosis.
AB  - BACKGROUND: This study aims to investigate whether nuclear beta-catenin
      overexpression at invasive front in rectal carcinoma is associated with lymph
      node metastasis and prognosis. METHODS: Immunohistochemistry was adopted to
      detect the expression of beta-catenin in rectal carcinoma and lymph node
      metastatic lesions. Spearman's rank correlation analysis and Tukey's test were
      used to evaluate the association between nuclear beta-catenin expression at
      invasive front in rectal carcinoma and lymph node metastasis. Kaplan-Meier method
      and multivariate Cox regression model were used to evaluate the prognostic value
      of nuclear beta-catenin overexpression at invasive front in rectal carcinoma for
      disease-free survival (DFS) and overall survival (OS). RESULTS: Overexpression of
      nuclear beta-catenin at the invasive front in rectal carcinoma in stage III-N2
      was significantly higher than that in stage III-N1 (73.4 vs. 40.4 %, P < 0.001).
      Nuclear beta-catenin expression at the invasive front in rectal carcinoma was
      associated with the expression of nuclear beta-catenin in corresponding lymph
      node metastatic lesions (r = 0.297, P < 0.001). Overexpression of nuclear beta
      catenin at the invasive front in rectal carcinoma was correlated with the number
      of metastatic lymph nodes (P < 0.001). Patients with nuclear beta-catenin
      overexpression at the invasive front in rectal carcinoma had poor DFS (P = 0.002)
      and OS (P = 0.003). Moreover, overexpression of nuclear beta-catenin at the
      invasive front was an independent prognosticator for unfavorable DFS and OS (P =
      0.002 and 0.001). CONCLUSIONS: Our findings suggest that overexpression of
      nuclear beta-catenin at the invasive front in rectal carcinoma may be a useful
      marker to evaluate lymph node metastasis, as well as a promising predictor of
      poor prognosis.

PMID- 24043497
TI  - Efficacy of rapamycin against glioblastoma cancer stem cells.
AB  - PURPOSE: The cancer stem cell (CSC) hypothesis suggests a hierarchical
      organization of cells within the tumor, in which only a subpopulation of stem
      like cells is responsible for the rise and progression of the tumor.
      Glioblastomas (GBM), a lethal brain tumor, may contain a variable proportion of
      active CSCs. On the other hand, the phosphatidylinositol 3-kinase (PI3
      K)/Akt/mammalian target of rapamycin (mTOR) pathway is highly active in up to 70
      % of GBM. The kinase mTOR is a key component of the PI3K pathway that mediates
      the regulation of growth and cell survival signaling. However, clinical trials
      with rapamycin, an effective inhibitor of mTOR, have not been up to the created
      expectations and a plausible explanation is missing. In this work, we analyze the
      effect of rapamycin on the GBM-CSC population. METHODS: The efficacy of rapamycin
      in vitro was tested on two primary cell lines derived from human GBM surgical
      resections that fulfill the criteria to be considered as CSCs. We confirmed the
      inhibition state of the PI3K/Akt/mTOR pathway analyzing the mTOR direct target
      ribosomal protein S6. We assayed the growth rate, CD133 expression and ability of
      forming colonies in soft agar of the CSCs under different doses of rapamycin. The
      efficacy of rapamycin in vivo was assayed in a CSCs-based orthotopic xenograft.
      RESULTS AND CONCLUSIONS: We report the efficacy of rapamycin by reducing CSCs
      proliferation and tumorigenic potential in vitro. Despite these encouraging
      results, the efficacy in vivo was very poor. This finding confirms the limited
      use of rapamycin as a monotherapy for glioblastomas.

PMID- 24043498
TI  - Marked elevation of adrenal steroids, especially androgens, in saliva of
      prepubertal autistic children.
AB  - Autism is diagnosed on the basis of behavioral manifestations, but its biomarkers
      are not well defined. A strong gender bias typifying autism (it is 4-5 times more
      prevalent in males) suggests involvement of steroid hormones in autism
      pathobiology. In order to evaluate the potential roles of such hormones in
      autism, we compared the salivary levels of 22 steroids in prepubertal autistic
      male and female children from two age groups (3-4 and 7-9 years old) with those
      in healthy controls. The steroids were analyzed using gas chromatography-mass
      spectrometry and radioimmunoassay. Statistical analysis (ANOVA) revealed that
      autistic children had significantly higher salivary concentrations of many
      steroid hormones (both C21 and C19) than control children. These anomalies were
      more prominent in older autistic children and in boys. The levels of androgens
      (androstenediol, dehydroepiandrosterone, androsterone and their polar conjugates)
      were especially increased, indicative of precocious adrenarche and predictive of
      early puberty. The concentrations of the steroid precursor, pregnenolone, and of
      several pregnanolones were also higher in autistic than in healthy children, but
      cortisol levels were not different. Some steroids, whose levels are raised in
      autism (allopregnanolone, androsterone, pregnenolone, dehydroepiandrosterone and
      their sulfate conjugates) are neuroactive and modulate GABA, glutamate, and
      opioid neurotransmission, affecting brain development and functioning. These
      steroids may contribute to autism pathobiology and symptoms such as elevated
      anxiety, sleep disturbances, sensory deficits, and stereotypies among others. We
      suggest that salivary levels of selected steroids may serve as biomarkers of
      autism pathology useful for monitoring the progress of therapy.

PMID- 24043499
TI  - Effects of structural and dynamic family characteristics on the development of
      depressive and aggressive problems during adolescence. The TRAILS study.
AB  - Both structural (i.e., SES, familial psychopathology, family composition) and
      dynamic (i.e., parental warmth and rejection) family characteristics have been
      associated with aggressive and depressive problem development. However, it is
      unclear to what extent (changes in) dynamic family characteristics have an
      independent effect on problem development while accounting for stable family
      characteristics and comorbid problem development. This issue was addressed by
      studying problem development in a large community sample (N = 2,230; age 10-20)
      of adolescents using Linear Mixed models. Paternal and maternal warmth and
      rejection were assessed via the Egna Minnen Betraffande Uppfostran for Children
      (EMBU-C). Aggressive and depressive problems were assessed via subscales of the
      Youth/Adult Self-Report. Results showed that dynamic family characteristics
      independently affected the development of aggressive problems. Moreover, maternal
      rejection in preadolescence and increases in paternal rejection were associated
      with aggressive problems, whereas decreases in maternal rejection were associated
      with decreases in depressive problems over time. Paternal and maternal warmth in
      preadolescence was associated with fewer depressive problems during adolescence.
      Moreover, increases in paternal warmth were associated with fewer depressive
      problems over time. Aggressive problems were a stable predictor of depressive
      problems over time. Finally, those who increased in depressive problems became
      more aggressive during adolescence, whereas those who decreased in depressive
      problems became also less aggressive. Besides the effect of comorbid problems,
      problem development is to a large extent due to dynamic family characteristics,
      and in particular to changes in parental rejection, which leaves much room for
      parenting-based interventions.

PMID- 24043500
TI  - Anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with
      cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis is an autosomal recessive multisystem disorder with
      an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary
      aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity
      with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of
      treatment includes corticosteroids and itraconazole. The treatment with
      corticosteroids for prolonged periods of time, or repeatedly for exacerbations of
      allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The
      monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely
      allergic asthmatics. The drug is given as a subcutaneous injection every two to
      four weeks. Since allergic bronchopulmonary aspergillosis is also a condition
      resulting from hypersensitivity to specific allergens, as in asthma, it may be a
      candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy,
      using agents like omalizumab, may be a potential therapy for allergic
      bronchopulmonary aspergillosis in people with cystic fibrosis. OBJECTIVES: To
      evaluate the efficacy and adverse effects of anti-IgE therapy for allergic
      bronchopulmonary aspergillosis in people with cystic fibrosis. SEARCH METHODS: We
      searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic
      database searches and handsearching of journals and conference abstract books. We
      also searched the reference lists of relevant articles and reviews. Last search:
      21 January 2013.We searched the ongoing trial registry clinicaltrials.gov for any
      ongoing trials. Latest search for clinicaltrials.gov: 22 February 2013. SELECTION
      CRITERIA: Randomized and quasi-randomized controlled trials comparing anti-IgE
      therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis
      in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data and assessed the risk of bias in the included study.
      They planned to perform data analysis using Review Manager 5.1. MAIN RESULTS:
      Only one trial enrolling 14 patients was eligible for inclusion in the review.
      The study was terminated prematurely and complete data were not available. We
      contacted the study investigator and were told that the study was terminated due
      to the inability to recruit patients into the study despite all reasonable
      attempts. One or more serious side effects were encountered in six out of nine
      (66.67%) and one out of five (20%) patients in omalizumab group and placebo group
      respectively. AUTHORS' CONCLUSIONS: There is lack of evidence for the efficacy
      and safety of anti-IgE (omalizumab) therapy in patients with cystic fibrosis and
      allergic bronchopulmonary aspergillosis. There is a need for large prospective
      randomized controlled trials of anti-IgE therapy in people with cystic fibrosis
      and allergic bronchopulmonary aspergillosis with both clinical and laboratory
      outcome measures such as steroid requirement, allergic bronchopulmonary
      aspergillosis exacerbations and lung function.

PMID- 24043501
TI  - Treatment of Tourette syndrome.
AB  - Tourette's syndrome (TS) consists of chronic motor and phonic tics and
      characteristically begins in childhood. The tics can be disabling and commonly
      associated behavioral comorbities such as attention deficit hyperactivity
      disorder (ADHD) and obsessive-compulsive disorder (OCD), can also cause problems
      in daily functioning. The underlying etiology and neurobiology of TS remain
      unknown although genetic factors appear to be important, cortical control of
      basal ganglia motor function appears to be disturbed and neurochemical
      abnormalities, particularly involving dopamine neurotransmission, are likely
      present. The treatment of TS involves appropriate education and support. Tics can
      be treated with habit reversal cognitive behavioral therapy, medications (most
      commonly alpha agonists and antipsychotics), local intramuscular injections of
      botulinum toxin and some severe, refractory cases have responded to deep brain
      stimulation surgery (DBS). It is important to appropriately diagnose and treat
      comorbid behavioral disorders that are disrupting function. OCD can be treated
      with cognitive behavioral therapy, selective serotonin reuptake inhibitors, and
      atypical antipsychotics. DBS has become a treatment option for patients with
      disabling OCD despite other therapies. ADHD is treated with appropriate classroom
      accommodations, behavioral therapy, alpha agonists, atomoxetine or
      methylphenidate-containing stimulant drugs. 

PMID- 24043502
TI  - Standard inocula preparations reduce the bacterial diversity and reliability of
      regulatory biodegradation tests.
AB  - OECD ready biodegradability tests have been central to understanding the
      biodegradation of chemicals from a regulatory perspective for many decades. They
      are not fit for contemporary prioritisation of chemicals based on persistence,
      however, due to the low concentration of inocula used, short duration and high
      variability between tests. Two OECD standard inoculum pretreatment methods
      (settlement and filtration) were investigated to observe their effect on the
      probability of biodegradation and associated changes in bacterial community
      structure and diversity of inocula sourced from the activated sludge process of
      wastewater treatment plants. Both settlement and filtration were shown to
      dramatically and significantly reduce the probability and increase the
      variability of biodegradation of 4-nitrophenol compared to the use of unprocessed
      inocula. These differences were associated with a significant hundred-fold
      reduction in cell numbers and solids content and a significant shift in bacterial
      community structure that was sometimes accompanied by significant reductions in
      detectable operational taxonomic unit richness and evenness. The natural
      variation (between different environments) and variation due to differential
      selection of bacterial communities (by different pretreatment methods) is offered
      as an explanation for the historical high variability in standard OECD ready
      biodegradability tests. 

PMID- 24043503
TI  - Adaptation strategies and referencing trial of Scots and black pine populations
      subjected to heavy metal pollution.
AB  - The impact of industrial heavy metal pollution on Scots pine (Pinus sylvestris
      L.) and black pine (Pinus nigra Arn.) populations was investigated. Sampled pine
      stands, which were located in Upper Silesia (southern Poland) in an area strongly
      polluted by heavy metals, consisted of resistant and sensitive trees. To evaluate
      the adaptation process, genetic structure and diversity was tested using isozyme
      analysis. Higher levels of Zn, Pb, Cd and Cu were detected in needles of
      sensitive trees compared with resistant ones. With respect to morphology, Scots
      pines were more distinctly impaired than black pines. Although black pines had
      lower heavy metal concentrations, levels in 1-year-old needles, other than Cu,
      significantly exceeded "reference plant" values (Markert 1994). In both species,
      resistant trees demonstrated a lower degree of genetic variation than metal
      sensitive trees with respect to some enzyme loci (SHDH A, PGI, PGM, MDH C and
      DIA). This observation was corroborated in sensitive trees by the smaller number
      of identified alleles and alleles per locus, absence of private alleles and
      significant excess of homozygotes in relation to expected Hardy-Weinberg
      equilibrium values. Assuming that only resistant trees of both species survive
      under conditions of prolonged soil contamination, the observed genetic structure
      implies that remaining populations will be depleted of some alleles of unknown
      adaptive value to future selection pressures. Genetic changes induced by heavy
      metals suggest an important role for specific enzymes-FEST, SHDH A and B, GOT B
      and PGI-in the adaptation process. Our results may serve as a basis for selection
      and propagation of individuals appropriate for re-cultivation of areas chemically
      degraded by industrial activity.

PMID- 24043504
TI  - Adaptation of the Daphnia sp. acute toxicity test: miniaturization and
      prolongation for the testing of nanomaterials.
AB  - Manufacturing of nanomaterials (NMs) is often complex and expensive, and their
      environmental risks are poorly understood or even unknown. An economization of
      testing NMs is therefore desirable, which can be achieved by miniaturizing test
      systems. However, the downsizing of test vessels and volumes can enlarge the
      surface/volume ratio (SVR) which in turn can affect the bioavailable
      concentration of adsorbing substances like NMs. The present study focused on the
      miniaturization of the acute toxicity test with Daphnia magna. The adaptations
      were verified with three reference substances, the non-adsorbing potassium
      dichromate (K2Cr2O7) and as potentially highly-adsorbing substances silver
      nanoparticles (AgNPs) and silver nitrate (AgNO3). The miniaturized test was
      conducted in 24-well microtiter plates (MT) and simultaneously compared to the
      OECD standard test (ST). Furthermore, the test duration was prolonged from 48 to
      96 h since NMs tend to show effects only after extended exposure. The toxicity of
      K2Cr2O7 and AgNPs continued to increase within the prolonged test span. The test
      comparisons with K2Cr2O7 did not reveal any significant differences between ST
      and MT. AgNO3 toxicity was significantly decreased in MT compared to ST due to
      the enlarged SVR. The toxicity of AgNPs in MT after 24 h was equal to ST.
      Contrary to our expectations an exposure longer than 24 h resulted in an increase
      of AgNP toxicity in MT, possibly due to enhanced dissolution of silver.
      Microtiter plates are appropriate alternative test vessels for the Daphnia sp.
      acute toxicity test; thus, its miniaturization is feasible. The enlarged SVR has
      to be taken into account since it can affect the toxicity of potentially
      adsorbing substances. Furthermore, the standard test duration of 48 h might
      underestimate the toxicity of many substances, especially of NMs.

PMID- 24043505
TI  - The short-term effects of a routine poisoning campaign on the movements and
      detectability of a social top-predator.
AB  - Top-predators can be important components of resilient ecosystems, but they are
      still controlled in many places to mitigate a variety of economic, environmental
      and/or social impacts. Lethal control is often achieved through the broad-scale
      application of poisoned baits. Understanding the direct and indirect effects of
      such lethal control on subsequent movements and behaviour of survivors is an
      important pre-requisite for interpreting the efficacy and ecological outcomes of
      top-predator control. In this study, we use GPS tracking collars to investigate
      the fine-scale and short-term movements of dingoes (Canis lupus dingo and other
      wild dogs) in response to a routine poison-baiting program as an example of how a
      common, social top-predator can respond (behaviourally) to moderate levels of
      population reduction. We found no consistent control-induced differences in home
      range size or location, daily distance travelled, speed of travel, temporal
      activity patterns or road/trail usage for the seven surviving dingoes we
      monitored immediately before and after a typical lethal control event. These data
      suggest that the spatial behaviour of surviving dingoes was not altered in ways
      likely to affect their detectability, and if control-induced changes in dingoes'
      ecological function did occur, these may not be related to altered spatial
      behaviour or movement patterns. 

PMID- 24043506
TI  - Assessing the effects of heavy metal contamination on the proteome of the moss
      Pseudoscleropodium purum cross-transplanted between different areas.
AB  - Protein expression was assessed in samples of Pseudoscleropodium purum cross
      transplanted between one unpolluted (UNP) and two polluted (POLL) sites. Firstly,
      the level of expression (LE) of 17 proteins differed between native mosses from
      both types of sites, but differences were only maintained throughout the
      experiment for 5 of them. The LE of these five proteins changed over time in
      mosses transplanted from UNP to POLL and vice versa, becoming similar to that in
      autotransplants. However, these changes occurred slower than changes in the heavy
      metal concentrations measured in the same samples, and therefore they were not
      related to atmospheric pollution. Although the proteins identified were
      associated with moss metabolism, the expected growth reduction in samples
      autotransplanted within POLL (as a result of the down-regulation of
      photosynthesis-related proteins), did not occur. This supports the hypothesis
      that mosses growing in polluted areas adapt to heavy metal pollution and are able
      to reduce/overcome their toxic effects (i.e., reduced growth). Nevertheless,
      further specific research must be carried out to identify the proteins involved
      in this type of response, as lack of information on the bryophyte genome
      precludes us from reaching further conclusions. 

PMID- 24043507
TI  - Thymol as an alternative to pesticides: persistence and effects of Apilife Var on
      the phototactic behavior of the honeybee Apis mellifera.
AB  - Thymol is a natural substance increasingly used as an alternative to pesticides
      in the fight against the Varroa destructor mite. Despite the effectiveness of
      this phenolic monoterpene against Varroa, few articles have covered the negative
      or side effects of thymol on bees. In a previous study, we have found an
      impairment of phototaxis in honeybees following application of sublethal doses of
      thymol-lower or equal to 100 ng/bee-under laboratory conditions. The present work
      shows the same behavioral effects on bees from hives treated with Apilife Var(r),
      a veterinary drug containing 74 % thymol, with a decrease in phototactic behavior
      observed 1 day after treatment. Thus, thymol causes disruption of bee phototactic
      behavior both under laboratory conditions as well as in beehives. The bee
      exposure dose in treated hives was quantified using gas chromatography coupled to
      mass spectrometry (GC-MS), giving a median value of 4.3 MUg per body 24 h after
      treatment, with 11 ng in the brain. The thymol level in 20 organic waxes from
      hives treated with Apilife Var(r) was also measured and showed that it persists
      in waxes (around 10 mg/kg) 1 year after treatment. Thus, in the light of (1)
      behavioral data obtained under laboratory conditions and in beehives, (2) the
      persistence of thymol in waxes, and (3) the high load on bees, it would appear
      important to study the long-term effects of thymol in beehives.

PMID- 24043508
TI  - Age-dependent impaired neurogenic differentiation capacity of dental stem cell is
      associated with Wnt/beta-catenin signaling.
AB  - Two kinds of dental stem cells (DSCs), dental pulp stem cells (DPSCs) and stem
      cells from human-exfoliated deciduous teeth (SHED), have been identified as novel
      populations of mesenchymal stem cells that can be induced to differentiate into
      osteoblasts, chondrocytes, adipocytes, and neuron-like cells in vitro. As we
      know, both of them originate from the neural crest, but have distinct
      characteristics and functions in vitro and in vivo. The regeneration potential of
      DSCs declines with advanced age; however, the mechanism of the impaired potential
      in DSCs has not been fully explored. In this study, we investigated whether
      declined neurogenic differentiation capacity is associated with an altered
      expression of Wnt signaling-related proteins in vitro. We compared stem cells
      isolated from human dental pulp in two age groups: the exfoliated deciduous teeth
      (5-12 years), and the third permanent teeth (45-50 years). We found that the
      expression levels of neuron markers, such as betaIII-tubulin, microtubule
      associated protein 2(MAP2), tyrosine hydroxylase (TH), and Nestin were lower in
      the DPSCs group compared with that in the SHED group; however, in supplementation
      with human recombinant Wnt1 in the medium, the DPSCs were prone to neural
      differentiation and expressed higher levels of neurogenic markers. In summary,
      our study demonstrated that Wnt/beta-catenin signaling may play a vital role in
      the age-dependent neural differentiation of DSCs. Therefore, DSCs may provide an
      ideal source of stem cells that can further extend their therapeutic application
      in nerve injury and neurodegenerative diseases.

PMID- 24043509
TI  - Extracting phonological patterns for L2 word learning: the effect of poor
      phonological awareness.
AB  - An implicit word learning paradigm was designed to test the hypothesis that
      children who came to the task of L2 vocabulary acquisition with poorer L1
      phonological awareness (PA) are less capable of extracting phonological patterns
      from L2 and thus have difficulties capitalizing on this knowledge to support L2
      vocabulary learning. A group of Chinese-speaking six-grade students took a multi
      trial L2 (English) word learning task after being exposed to a set of familiar
      words that rhymed with the target words. Children's PA was measured at grade 3.
      Children with relatively poorer L1 PA and those with better L1 PA did not differ
      in identifying the forms of the new words. However, children with poorer L1 PA
      demonstrated reduced performance in naming pictures with labels that rhymed with
      the pre-exposure words than with labels that did not rhyme with the pre-exposure
      words. Children with better L1 PA were not affected by the recurring rime shared
      by the pre-exposure words and the target words. These findings suggest that poor
      L1 PA may impede L2 word learning via difficulty in abstracting phonological
      patterns away from L2 input to scaffold word learning. 

PMID- 24043510
TI  - Modality-dependent and -independent factors in the organisation of the signed
      language lexicon: insights from semantic and phonological fluency tasks in BSL.
AB  - We used fluency tasks to investigate lexical organisation in Deaf adults who use
      British sign language (BSL). The number of responses produced to semantic
      categories did not differ from reports in spoken languages. However, there was
      considerable variability in the number of responses across phonological
      categories, and some signers had difficulty retrieving items. Responses were
      richly clustered according to semantic and/or phonological properties. With
      respect to phonology, there was significantly more clustering around the
      parameters "handshape" and "location" compared to "movement". We conclude that
      the BSL lexicon is organised in similar ways to the lexicons of spoken languages,
      but that lexical retrieval is characterised by strong links between semantics and
      phonology; movement is less readily retrieved than handshape and location; and
      phonological fluency is difficult for signers because they have little
      metaphonological awareness in BSL and because signs do not display the onset
      salience that characterises spoken words. 

PMID- 24043512
TI  - Association of genotypes at the matrix metalloproteinase (MMP) loci with carotid
      IMT and presence of carotid and femoral atherosclerotic plaques.
AB  - We aimed to test the association between matrix metalloproteinase (MMP) genetic
      polymorphisms and (a) intima-media thickness in the common carotid (IMTcc) and
      (b) the presence of plaques in the carotid and femoral bifurcations. Carotid and
      femoral bifurcations were scanned with ultrasound in 762 Cypriot community
      dwellers (46% men) over the age of 40 years. IMTcc and the presence of plaques
      were recorded. The MMP1 1G/2G, MMP3 5A/6A, MMP7 -181A>G, MMP9 R279Q, and MMP12 
      82A>G polymorphisms were determined with the TaqMan method. In men, the presence
      of plaques in any bifurcation was associated with the MMP9 279Q allele (OR
      adjusted=4.50; 95% CI=2.0 to 10.1; p<0.001) and the MMP7 -181A allele was
      associated with the presence of femoral plaques (OR adjusted=2.61; 95% CI=1.36 to
      4.99; p=0.004). In women, the presence of femoral plaques was associated with the
      MMP12 -82G allele (OR adjusted=1.9; 95% CI=1.14 to 3.16; p=0.014). Our results
      suggest that the effect of common MMP genotypes on plaque presence may be site-
      and sex-dependent.

PMID- 24043511
TI  - Syncoilin is an intermediate filament protein in activated hepatic stellate
      cells.
AB  - Hepatic stellate cells (HSCs) play an important role in several
      (patho)physiologic conditions in the liver. In response to chronic injury, HSCs
      are activated and change from quiescent to myofibroblast-like cells with
      contractile properties. This shift in phenotype is accompanied by a change in
      expression of intermediate filament (IF) proteins. HSCs express a broad, but
      variable spectrum of IF proteins. In muscle, syncoilin was identified as an alpha
      dystrobrevin binding protein with sequence homology to IF proteins. We
      investigated the expression of syncoilin in mouse and human HSCs. Syncoilin
      expression in isolated and cultured HSCs was studied by qPCR, Western blotting,
      and fluorescence immunocytochemistry. Syncoilin expression was also evaluated in
      other primary liver cell types and in in vivo-activated HSCs as well as total
      liver samples from fibrotic mice and cirrhotic patients. Syncoilin mRNA was
      present in human and mouse HSCs and was highly expressed in in vitro- and in vivo
      activated HSCs. Syncoilin protein was strongly upregulated during in vitro
      activation of HSCs and undetectable in hepatocytes and liver sinusoidal
      endothelial cells. Syncoilin mRNA levels were elevated in both CCl4- and common
      bile duct ligation-treated mice. Syncoilin immunocytochemistry revealed
      filamentous staining in activated mouse HSCs that partially colocalized with
      alpha-smooth muscle actin, beta-actin, desmin, and alpha-tubulin. We show that in
      the liver, syncoilin is predominantly expressed by activated HSCs and displays
      very low-expression levels in other liver cell types, making it a good marker of
      activated HSCs. During in vitro activation of mouse HSCs, syncoilin is able to
      form filamentous structures or at least to closely interact with existing
      cellular filaments. 

PMID- 24043513
TI  - ADad 3: the epidemiology of Anxiety Disorders among adolescents in a rural
      community population in India.
AB  - OBJECTIVES: Despite being the most common mental health concern, there is paucity
      of literature on the epidemiology of anxiety disorders among the adolescent
      population in India. This study aimed to estimate the period prevalence of
      Anxiety Disorders (AD) among 11 to 19 y old adolescents in India. METHODS: A
      representative sample of adolescents (N = 500) from a rural community in Southern
      India was assessed for the period prevalence of all and specific Anxiety
      Disorders using Screen for Child Anxiety Related Emotional Disorders (SCARED),
      and confirmed in a subsequent interview with Schedule for Affective Disorders and
      Schizophrenia for School-Age Children/Present and Lifetime Version (K-SADS-PL).
      RESULTS: The prevalence for all AD using the international, Indian SCARED cut
      offs and DSM-IV-TR criteria was 8.6 % (boys = 2%; girls = 6.6%), 25.8% (boys =
      6.6%; girls = 19.2%) and 14.4 % (boys = 4.8%; girls = 9.6%) respectively. There
      were significant gender differences in the prevalence for all Anxiety Disorders
      (chi (2) = 3.61, df = 1; P < 0.05), Separation Anxiety Disorder (chi (2) = 22.27,
      df = 1; P < 0.001) and Social Anxiety Disorder (chi(2) = 4.29, df = 1; P < 0.03).
      Significant age difference in the prevalence of Panic Disorder (chi(2) = 10.32;
      df = 1; P = 0.00) and Generalized Anxiety Disorder (chi(2) = 5.87; df = 1; P =
      0.05) was noted. CONCLUSIONS: The prevalence of Anxiety Disorders in South Indian
      adolescents was higher than found in the western literature. Prevalence of
      specific AD was age and gender specific. Adolescent and mental health policies
      must integrate anxiety disorder of public health significance.

PMID- 24043514
TI  - ADad 8: School Phobia and Anxiety Disorders among adolescents in a rural
      community population in India.
AB  - OBJECTIVE: School Phobia (SP), although is not a formal psychiatric diagnosis, is
      widely prevalent debilitating phenomenon with a gamut of underlying psychiatric
      conditions in an overwhelming majority of cases. This study documents the
      prevalence, symptom presentation and the relationship between the various
      subtypes of Anxiety Disorders (AD) and School Phobia. METHODS: In a prospective
      community survey of 500 adolescents, independent raters administered the Screen
      for Child Anxiety Related Emotional Disorders and Schedule for Affective
      Disorders and Schizophrenia for School-Age Children/Present and Lifetime to
      identify SP and subtype of AD respectively. Descriptive statistics for the
      prevalence and symptom presentation, Spearman's Correlation test, Independent t
      tests, on-way ANOVA and Chi-square tests were done to compare the prevalence and
      severity of School Phobia among various age groups and gender. Univariate and
      multivariate analyses were done for documenting the relationship between the
      School Phobia and Anxiety Disorders. RESULTS: School Phobia was noted in 4.8% of
      adolescents. Although age was related to SP, gender, school grade the adolescent
      was attending and family structure were not related to SP. Somatic symptoms were
      more often noted than cognitive-emotional symptoms among adolescents with SP.
      Panic Disorder (OR = 8.62), Social Anxiety Disorder (OR = 8.63), and Separation
      Anxiety Disorder (OR = 6.26), were significantly related to SP. CONCLUSIONS:
      School Phobia is noted in a significant proportion of adolescents in the
      community. Anxiety Disorder is a major underlying factor resulting in SP.
      Community and clinical intervention and service models should include anxiety
      alleviation methods in adolescents with School Phobia.

PMID- 24043515
TI  - ADad 10: the impairment in Anxiety Disorders among adolescents in a rural
      community population in India.
AB  - OBJECTIVES: There is significant paucity of studies on the impairment associated
      with Anxiety Disorders (AD) among adolescents. This study focuses on the
      prevalence and pattern of impairment as well as impairment in the context of
      severity of AD, co-morbidities, suicide, age and gender in this population.
      METHODS: In a prospective community survey of 500 adolescents, independent raters
      administered the Screen for Child Anxiety Related Emotional Disorders (SCARED)
      and Schedule for Affective Disorders and Schizophrenia for School-Age
      Children/Present and Lifetime to collect the required data. Descriptive
      statistics and Chi-square tests were done to evaluate the prevalence and profile
      of impairment, compare the impairment among different types of AD, severity of
      AD, number of co-morbidities, age and gender on impairment, effect of impairment
      on the need for suicide prevention. RESULTS: Impairment in adolescents with AD
      was a rule, noted in 94.4%. Irrespective of the type of AD diagnosed, impairment
      at home was significant in adolescents with AD. The presentation of impairment
      among different Anxiety Disorders was different with different functional
      settings. Severity of AD and the number of co-morbidities was related to the
      impairment. Need for suicide related interventions were not different in those
      with and without impairment. Age and gender did not influence the presence of
      impairment. CONCLUSIONS: Anxiety Disorders among adolescents in India result in
      significant functional impairment. Clinically, in this population assessment of
      impairment is required. Community policies and plans should have special
      management strategy to address impairment in adolescents with Anxiety Disorders.

PMID- 24043519
TI  - NCO(-), a key fragment upon dissociative electron attachment and electron
      transfer to pyrimidine bases: site selectivity for a slow decay process.
AB  - We report gas phase studies on NCO(-) fragment formation from the nucleobases
      thymine and uracil and their N-site methylated derivatives upon dissociative
      electron attachment (DEA) and through electron transfer in potassium collisions.
      For comparison, the NCO(-) production in metastable decay of the nucleobases
      after deprotonation in matrix assisted laser desorption/ionization (MALDI) is
      also reported. We show that the delayed fragmentation of the dehydrogenated
      closed-shell anion into NCO(-) upon DEA proceeds few microseconds after the
      electron attachment process, indicating a rather slow unimolecular decomposition.
      Utilizing partially methylated thymine, we demonstrate that the remarkable site
      selectivity of the initial hydrogen loss as a function of the electron energy is
      preserved in the prompt as well as the metastable NCO(-) formation in DEA. Site
      selectivity in the NCO(-) yield is also pronounced after deprotonation in MALDI,
      though distinctly different from that observed in DEA. This is discussed in terms
      of the different electronic states subjected to metastable decay in these
      experiments. In potassium collisions with 1- and 3-methylthymine and 1- and 3
      methyluracil, the dominant fragment is the NCO(-) ion and the branching ratios as
      a function of the collision energy show evidence of extraordinary site
      selectivity in the reactions yielding its formation. 

PMID- 24043520
TI  - Gas-phase structure of amyloid-beta (12-28) peptide investigated by infrared
      spectroscopy, electron capture dissociation and ion mobility mass spectrometry.
AB  - The gas-phase structures of doubly and triply protonated Amyloid-beta12-28
      peptides have been investigated through the combination of ion mobility (IM),
      electron capture dissociation (ECD) mass spectrometry, and infrared multi-photon
      dissociation (IRMPD) spectroscopy together with theoretical modeling. Replica
      exchange molecular dynamics simulations were conducted to explore the
      conformational space of these protonated peptides, from which several classes of
      structures were found. Among the low-lying conformers, those with predicted
      diffusion cross-sections consistent with the ion mobility experiment were further
      selected and their IR spectra simulated using a hybrid quantum
      mechanical/semiempirical method at the ONIOM DFT/B3LYP/6-31 g(d)/AM1 level. In
      ECD mass spectrometry, the c/z product ion abundance (PIA) has been analyzed for
      the two charge states and revealed drastic differences. For the doubly protonated
      species, N - Calpha bond cleavage occurs only on the N and C terminal parts,
      while a periodic distribution of PIA is clearly observed for the triply charged
      peptides. These PIA distributions have been rationalized by comparison with the
      inverse of the distances from the protonated sites to the carbonyl oxygens for
      the conformations suggested from IR and IM experiments. Structural assignment for
      the amyloid peptide is then made possible by the combination of these three
      experimental techniques that provide complementary information on the possible
      secondary structure adopted by peptides. Although globular conformations are
      favored for the doubly protonated peptide, incrementing the charge state leads to
      a conformational transition towards extended structures with 310- and alpha-helix
      motifs. 

PMID- 24043521
TI  - Gas-phase dissociation of homo-DNA oligonucleotides.
AB  - Synthetic modified oligonucleotides are of interest for diagnostic and
      therapeutic applications, as their biological stability, pairing selectivity, and
      binding strength can be considerably increased by the incorporation of unnatural
      structural elements. Homo-DNA is an oligonucleotide homologue based on dideoxy
      hexopyranosyl sugar moieties, which follows the Watson-Crick A-T and G-C base
      pairing system, but does not hybridize with complementary natural DNA and RNA.
      Homo-DNA has found application as a bioorthogonal element in templated chemistry
      applications. The gas-phase dissociation of homo-DNA has been investigated by ESI
      MS/MS and MALDI-MS/MS, and mechanistic aspects of its gas-phase dissociation are
      discussed. Experiments revealed a charge state dependent preference for the loss
      of nucleobases, which are released either as neutrals or as anions. In contrast
      to DNA, nucleobase loss from homo-DNA was found to be decoupled from backbone
      cleavage, thus resulting in stable products. This renders an additional stage of
      ion activation necessary in order to generate sequence-defining fragment ions.
      Upon MS(3) of the primary base-loss ion, homo-DNA was found to exhibit unspecific
      backbone dissociation resulting in a balanced distribution of all fragment ion
      series. 

PMID- 24043522
TI  - Artifacts induced by selective blanking of time-domain data in Fourier transform
      mass spectrometry.
AB  - Fourier transform mass spectrometry (FTMS) of the isolated isotopic distribution
      for a highly charged biomolecule produces time-domain signal containing large
      amplitude signal "beats" separated by extended periods of much lower signal
      magnitude. Signal-to-noise ratio for data sampled between beats is low because of
      destructive interference of the signals induced by members of the isotopic
      distribution. Selective blanking of the data between beats has been used to
      increase spectral signal-to-noise ratio. However, blanking also eliminates signal
      components and, thus, can potentially distort the resulting FT spectrum. Here, we
      simulate the time-domain signal from a truncated isotopic distribution for a
      single charge state of an antibody. Comparison of the FT spectra produced with or
      without blanking and with or without added noise clearly show that blanking does
      not improve mass accuracy and introduces spurious peaks at both ends of the
      isotopic distribution (thereby making it more difficult to identify
      posttranslational modifications and/or adducts). Although the artifacts are
      reduced by use of multiple Gaussian (rather than square wave) windowing, blanking
      appears to offer no advantages for identifying true peaks or for mass
      measurement. 

PMID- 24043523
TI  - Simulation of rarefied gas flows in atmospheric pressure interfaces for mass
      spectrometry systems.
AB  - The understanding of the gas dynamics of the atmospheric pressure interface is
      very important for the development of mass spectrometry systems with high
      sensitivity. While the gas flows at high pressure (>1 Torr) and low pressure
      (<10(-3) Torr) stages are relatively well understood and could be modeled using
      continuum and molecular flows, respectively, the theoretical modeling or numeric
      simulation of gas flow through the transition pressure stage (1 to 10(-3) Torr)
      remains challenging. In this study, we used the direct simulation Monte Carlo
      (DMSC) method to develop the gas dynamic simulations for the continuous and
      discontinuous atmospheric pressure interfaces (API), with different focuses on
      the ion transfer by gas flows through a skimmer or directly from the atmospheric
      pressure to a vacuum stage, respectively. The impacts by the skimmer location in
      the continuous API and the temporal evolvement of the gas flow with a
      discontinuous API were characterized, which provide a solid base for the
      instrument design and performance improvement. 

PMID- 24043524
TI  - [Preventive circumcision - european doctors doubt AAP report].

PMID- 24043525
TI  - [Bladder cancer - neoadjuvant therapy with cisplatin and gemcitabine].

PMID- 24043526
TI  - [Nephrolithiasis - characterization of kidney stones by CT].

PMID- 24043527
TI  - [Prostate cancer - soy has no effect].

PMID- 24043528
TI  - [Flexible ureterorenoscopey - ureteral wall injuries from ureteral access sheath
      insertion].

PMID- 24043529
TI  - [TOMAX - increased sexual satisfaction].

PMID- 24043530
TI  - [Kidney Forum].

PMID- 24043531
TI  - [Research impulses for personalized cancer therapies].

PMID- 24043532
TI  - [Hemostasis by botulinum toxic injection].

PMID- 24043533
TI  - [Generation Y - a new generation of employees changes the work world].

PMID- 24043534
TI  - [Patient education - death after insufficient information about risks: federal
      supreme court confirms acquittal of doctors].

PMID- 24043535
TI  - [Penile cancer - a challenge for modern uro-oncology].
AB  - Due to the low incidence of penile cancer in Europe and North America and often
      decentralised patient management, data on the treatment of penile cancer are very
      rare. Nevertheless, recently relevant data have become available for the
      improvement of the therapy especially for the primary tumours. Penile conserving
      surgery is becoming more important for early tumour stages. The management of
      lymph nodes plays a key role for the successful treatment of patients with penile
      cancer. An invasive lymph node staging is recommended for all patients with
      primary pT1G2 or higher tumours. Neoadjuvant chemotherapy followed by salvage
      lymphadenectomy has shown promising results in patients with large and/or fixed
      inguinal lymph node metastases. Due to the results of recent studies,
      cisplatin/taxan-based chemotherapy regimens have to be recommended. 

PMID- 24043536
TI  - [Does the surgeon have an influence on clinical voiding parameters and
      postoperative sexual function after TURP?].
AB  - BACKGROUND: Benign prostate syndrome (BPS) is a common phenomenon in the aging
      male. Transurethral resection of the prostate (TURP) remains the international
      standard of care for -patients requiring surgical intervention for BPS. Although
      the voiding improvement following TURP is well-documented, controversy exists
      regarding its effect on post-operative sexual function. In this study we
      investigated the possible influence of individual surgeons on clinical voiding
      parameters and post-operative sexual function after TURP. PATIENTS/MATERIALS AND
      METHODS: We analyzed 123 patients with a mean age of 70 years (46-88 years) who
      had undergone TURP secondary to BPS. To evaluate the clinical parameters,
      patients completed the IPSS and IIEF-15 questionnaires preoperatively and 1 year
      postoperatively. Additional parameters including urinary flow and post voiding
      residual volume were also collected. RESULTS: A statistically significant
      improvement in voiding function was noted postoperatively. The mean IPSS improved
      from 19.35 to 6.49 (p<0.05). Objective flow parameters also improved; Qmax 10.43
      19.46 mL/s (p<0.05) and residual volume 95-11 mL (p<0.05). The mean pre-operative
      prostate volume was 41.8 cm3. The mean resected tissue weight was 21.1 g. The pa
      tients showed no significant change in the frequency of their sexual activity
      following TURP, however IIEF-15 sexual function and erectile function scores
      declined mildly. This was statistically significant with pre-op IIEF-15=30.52 and
      post-op 26.24 (p<0.05). Comparing individual surgeons, no statistically
      significant difference was noted in IPSS and IIEF-15 functional outcome scores.
      Although significant differences existed in the total amount of resected tissue,
      the percentage of resected adenoma in relation to total prostate volume was not
      statistically significant. CONCLUSION: Overall, IPSS scores improved
      significantly following TURP and sexual function scored declined mildly. We
      detected no influence between surgeons on clinical voiding parameters and
      postoperative sexual function after TURP using the IPSS and IIEF-15
      questionnaires.

PMID- 24043537
TI  - [Carcinoma of the pararenal gland infiltrating the surrounding tissue and
      involving the inferior vena cava].
AB  - ?HISTORY AND ADMISSION FI NDINGS: A 61-year-old woman presented with a 2-month
      history of progressive deterioration, increasing exertional dyspnoea and pain in
      the right upper abdomen (past medical history: bronchial asthma and
      hypertension). The physical examination showed mild generalized weakness,
      tenderness in the right upper abdomen, and ascites. INVESTIGATIONS: Laboratory
      studies did not reveal any hormonal abnormalities. A CT angiogram revealed a mass
      of the right adrenal gland with distinct invasion into the inferior vena cava,
      and tumour thrombosis that extended proximally into the right atrium. Distally,
      the tumour ended at the caudate lobe of the liver with an extensive peripherally
      engulfed thrombus from the inferior vena cava down to the common iliac -veins.
      TREATMENT AND COURSE: An open right adrenalectomy with resection of the
      periadrenal tissue and exstirpation of the intracaval tumour thrombus (by
      cavotomy under digital occlusion of the blood flow from the vena cava into the
      right atrium - cardiac surgeon) was carried out with no significant postoperative
      complications. Subsequently, the patient underwent adjuvant mitotane therapy for
      3 years. So far, no recurrence has occurred during a course of 7 years.
      CONCLUSION: Tumour induced thrombotic occlusion of the inferior vena cava and
      other veins is rare, especially with right atrium involvement. In the absence of
      other effective treatment options, the combination of radical resection and
      adjuvant mitotane therapy remains the only successful curative treatment for
      primary invasive pararenal gland carcinoma.

PMID- 24043538
TI  - [Medical reviews of claims for damages and errors in urology].
AB  - In liability law, a medical review is considered to be an expert opinion that is
      provided at the request of those involved (patient or physician) of a course of
      treatment. It must be carried out according to defined criteria with the aim of
      providing a plausible basis for arbitration. This is achieved by means of an
      objective determination of the facts, a reasonable assessment of the error(s) and
      (where appropriate) a realistic description of the injury involved. The following
      fields should be covered in a concise review: conditions and procedures applied
      to the review, criteria to be used in the review, types of error that are
      possible during the treatment, assessment of the treatment errors committed,
      possible treatment errors that can occur in urology, conclusions to be drawn from
      the review. In summary, a medical assessment carried out in the course of claims
      for damages should provide a balanced assessment that takes into account the
      confidential relationship between the physician and patient. This means that the
      review procedure must be performed under the best possible conditions for
      professional standards and care.

PMID- 24043539
TI  - [Transurethral electroresection of the prostate (TURP)].

PMID- 24043540
TI  - Insight into the structural stability of wild type and mutants of the tobacco
      etch virus protease with molecular dynamics simulations.
AB  - The efficiency and high specificity of tobacco etch virus protease (TEVp) has
      made it widely used for cleavage of recombinant fusion proteins. However, TEVp
      suffers from a few intrinsic defects such as self-cleavage, poorly expressed in
      E. coli and less soluble. So some mutants were designed to improve it, such as
      S219V, T17S/N68D/I77V and L56V/S135G etc. MD simulations for the WT TEVp and its
      mutants were performed to explore the underlying dynamic effects of mutations on
      TEVp. Although the globular domains are fairly conserved, the three mutations
      have diverse effects on the dynamics properties of TEVp, including the elongation
      of beta-sheet, conversion of loop to helix and the flexibility of active core.
      Our present study indicates that the three mutants for TEVp can change their
      secondary structure and tend to form more helixes and sheets to improve
      stability. The study also helps us to understand the effects of some mutations on
      TEVp, provides us insights into the change of them at the atomic level and gives
      a potential rational method to design an improved protein.

PMID- 24043541
TI  - Exploring surface reactivity of phosphorous-doped (6,0) and (4,4) BC3 nanotubes:
      a DFT study.
AB  - We report a density functional theory study on the electronic structure
      properties of pristine and phosphorous-doped (6,0) and (4,4) single-walled BC3
      nanotubes (BC3NTs). We examine the usefulness of local reactivity descriptors to
      predict the reactivities of different carbon/boron atomic sites on the external
      surface of the tubes. Electrostatic potentials VS(r) and average local ionization
      energies IS(r) are computed on the surface of the investigated BC3NTs. A general
      feature of the systems considered here is that the magnitudes of negative VS(r)
      associated with carbon atoms tend to be stronger when the boron atom is
      substituted with a phosphorous atom. In order to verify the surface reactivity
      pattern based on the chosen reactivity descriptors, we calculated the reaction
      energies for the interaction of an H(+) ion or H radical with external surface of
      the (6,0) and (4,4) BC3NTs. It is clear that, for each nanotube studied, the
      reaction energies correlate well with the values of VS(r) and IS(r).

PMID- 24043542
TI  - Molecular interactions between fenoterol stereoisomers and derivatives and the
      beta2-adrenergic receptor binding site studied by docking and molecular dynamics
      simulations.
AB  - The beta2 adrenergic receptor (beta2-AR) has become a model system for studying
      the ligand recognition process and mechanism of the G protein coupled receptors
      activation. In the present study stereoisomers of fenoterol and some of its
      derivatives (N = 94 molecules) were used as molecular probes to identify
      differences in stereo-recognition interactions between beta2-AR and structurally
      similar agonists. The present study aimed at determining the 3D molecular models
      of the fenoterol derivative-beta2-AR complexes. Molecular models of beta2-AR have
      been developed by using the crystal structure of the human beta2-AR T4 lysozyme
      fusion protein with bound (S)-carazolol (PDB ID: 2RH1) and more recently reported
      structure of a nanobody-stabilized active state of the beta2-AR with the bound
      full agonist BI-167107 (PDB ID: 3P0G). The docking procedure allowed us to study
      the similarities and differences in the recognition binding site(s) for tested
      ligands. The agonist molecules occupied the same binding region, between TM III,
      TM V, TM VI and TM VII. The residues identified by us during docking procedure
      (Ser203, Ser207, Asp113, Lys305, Asn312, Tyr308, Asp192) were experimentally
      indicated in functional and biophysical studies as being very important for the
      agonist-receptor interactions. Moreover, the additional space, an extension of
      the orthosteric pocket, was identified and described. Furthermore, the molecular
      dynamics simulations were used to study the molecular mechanism of interaction
      between ligands ((R,R')- and (S,S')-fenoterol) and beta2-AR. Our research offers
      new insights into the ligand stereoselective interaction with one of the most
      important GPCR member. This study may also facilitate the design of improved
      selective medications, which can be used to treat, prevent and control heart
      failure symptoms.

PMID- 24043543
TI  - The intrinsic helical propensities of the helical fragments in prion protein
      under neutral and low pH conditions: a replica exchange molecular dynamics study.
AB  - Replica exchange molecular dynamics simulations in neutral and acidic aqueous
      solutions were employed to study the intrinsic helical propensities of three
      helices in both Syrian hamster (syPrP) and human (huPrP) prion proteins. The
      helical propensities of syPrP HA and huPrP HA are very high under both pH
      conditions, which implies that HA is barely involved in the helix-to-beta
      transition. The SyPrP HB chain has a strong tendency to adopt an extended
      conformation, which is possibly involved in the mechanism of infectious prion
      diseases in Syrian hamster. HuPrP HC has more of a preference for the extended
      conformation than huPrP HA and huPrP HB do, which leads to the conjecture that it
      is more likely to be the source of beta-rich structure for human prion protein.
      We also noticed that the presence of salt bridges is not correlated with helical
      propensity, indicating that salt bridges do not stabilize helices.

PMID- 24043544
TI  - Redox and Lewis acid-base activities through an electronegativity-hardness
      landscape diagram.
AB  - Chemistry is the science of bond making and bond breaking which requires
      redistribution of electron density among the reactant partners. Accordingly acid
      base and redox reactions form cardinal components in all branches of chemistry,
      e.g., inorganic, organic, physical or biochemistry. That is the reason it forms
      an integral part of the undergraduate curriculum all throughout the globe. In an
      electronegativity (chi)- hardness (eta) landscape diagram the diagonal chi = eta
      line separates reducing agents from oxidizing agents as well as Lewis acids from
      Lewis bases. While electronegativity is related to the degree of electron
      transfer between two reactants, hardness is related to the resistance to that
      process. Accordingly the electronegativities of oxidizing agents/Lewis acids are
      generally greater than the corresponding hardness values and the reverse is true
      for reducing agents/Lewis bases. Electrophiles and nucleophiles are also expected
      to follow similar trends.

PMID- 24043545
TI  - Easy methods to study the smart energetic TNT/CL-20 co-crystal.
AB  - 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) is a high
      energy nitramine explosive with high mechanical sensitivity. 2,4,6
      trinitrotoluene (TNT) is insensitive but by no means a high performance
      explosive. To reveal the significant importance and smart-material functionality
      of the energetic-energetic co-crystals, the stability, mechanical and explosive
      properties TNT/CL-20 co-crystal, TNT crystal and CL-20 crystal were studied. Non
      hydrogen bonded non-covalent interactions govern the structures of energetic
      energetic co-crystals. However, it is very difficult to accurately calculate the
      non-covalent intermolecular interaction energies. In this paper, the local
      conformation and the intricate non-covalent interactions were effectively mapped
      and analyzed from the electron density (rho) and its derivatives. The results
      show that the two components TNT and CL-20 are connected mainly by nitro-aromatic
      interactions, and nitro-nitro interactions. The steric interactions in TNT/CL-20
      could not be confronted with the attractive interactions. Moreover, the scatter
      graph of TNT crystal reveals the reason why TNT is brittle. The detailed
      electrostatic potential analysis predicted that the detonation velocities (D) and
      impact sensitivity for the compounds both increase in the sequence of CL-20 >
      TNT/CL-20 co-crystal > TNT. Additionally, TNT/CL-20 co-crystal has better
      malleability than its pure components. This demonstrates the capacity and the
      feasibility of realizing explosive smart materials by co-crystallization, even if
      strong hydrogen bonding schemes are generally lacking in energetic materials.

PMID- 24043546
TI  - Discovery of sigma-hole interactions involving ylides.
AB  - The positive electrostatic potentials (sigma-hole) have been found in ylides
      CH2XH3 (X = P, As, Sb) and CH2YH2 (Y = S, Se, Te), on the outer surfaces of group
      VA and VIA atoms, approximately along the extensions of the C-X and C-Y bonds,
      respectively. These electrostatic potentials suggest that the above ylides can
      interact with nucleophiles to form weak, directional noncovalent interactions
      similar to halogen bonding interactions. MP2 calculations have confirmed the
      formation of CH2XH3...HM complexes (X = P, As, Sb; M = BeH, ZnH, MgH, Li, Na).
      The interaction energies, interaction distances, topological properties (electron
      density and its Laplacian), and energy properties (kinetic electron energy
      density and potential electron energy density) at the X(1)...H(10) bond critical
      points are all correlated with the most negative electrostatic potential value of
      HM, indicating that electrostatic interactions play an important role in these
      weak X...H interactions. Similar to the halogen bonding interactions, weak
      interactions involving ylides may be significant in several areas such as organic
      synthesis, crystal engineering, and design of new materials.

PMID- 24043547
TI  - Dissociation of the X chromosome from the synaptonemal complex in the XY body of
      the rodent Galea musteloides.
AB  - The XY body from spermatocytes of the rodent Galea musteloides shows progressive
      changes of the synaptonemal complex (SC) axes and the X-chromatin during
      pachynema. There is a gross thickening of the X-axis and the formation of a large
      X chromosome loop at mid and late pachytene stages. The SC proteins synaptonemal
      complex protein 3 (SYCP3), synaptonemal complex protein 1, and synaptonemal
      complex central element protein 3 and the proteins breast cancer 1, MutL homolog
      1 (MLH1), and radiation-repair 51 (related to meiotic processes), the cohesin
      structural maintenance of chromosome 3, the centromeric protein (with CREST
      antibody), and the silenced chromatin (with phosphorylated (139ph) H2A histone
      family, member X (gamma-H2AX) antibody) were analyzed in this XY body. The thick
      X-axis, including the interstitial loop, becomes formed by four to six laminae
      showing a cross-striation with a periodicity of about 20 nm. The whole length of
      the gross X-axis shows no significant changes during pachynema, but the
      interstitial chromatin of the X chromosome and the X centromere are included in
      the large loop, and it becomes separated from the SC. A conventional SC formed by
      the Y-axis, a central region and a thin lateral element originally corresponding
      to the X-axis, remains undisturbed up to the end of pachynema. A single MLH1
      focus develops either at the distal or the proximal region of the loop end
      attached to the conventional SC. The chromatin surrounding the thickened axis is
      labeled with gamma-H2AX. It is shown that most of the SYCP3 protein associated
      with the X chromosome loop is not involved in the SC maintenance, but it is
      located with the cohesin axis separated from the SC proper.

PMID- 24043548
TI  - Identification of novel MicroRNA signatures linked to experimental autoimmune
      myasthenia gravis pathogenesis: down-regulated miR-145 promotes pathogenetic Th17
      cell response.
AB  - Emerging evidence demonstrates that miRNAs, a new family of key mRNA regulatory
      molecules, have crucial roles in controlling and modulating immunity. Their
      contribution to myasthenia gravis (MG), a T cell-dependent, antibody-mediated
      nervous system autoimmune disease, has not been thoroughly investigated. In the
      present study, using a highly sensitive microarray-based approach, we identified
      11 miRNAs with differential expression between Peripheral Blood Mononuclear Cells
      (PBMC) from experimental autoimmune MG (EAMG) rats and control rats. miR-145 is
      one of the most significantly down-regulated miRNAs in PBMC from EAMG rats. Down
      regulation of miR-145 expression was confirmed in PBMC and CD4+CD25- T cells (T
      effector cells) from both EAMG rats and MG patients by real-time PCR.
      Bioinformatics target prediction identified two crucial immune-related molecules
      CD28 and NFATc1, as putative targets of miR-145. Furthermore, miR-145 inhibited
      CD28 and NFATc1 expression by directly targeting their 3'-UTRs, which was
      abolished by mutation of the miR-145 and CD28/NFATc1 binding sites. In vitro up
      regulation of miR-145 in CD4+ T cells can significantly reduce CD28 protein
      levels accompanied by decreased proliferative response. In a dendritic cell (DC)
      T cell coculture system, overexpression of miR-145 in AChR-specific CD4+ T cells
      suppresses NFATc1 expression and T Helper 17 cells level. Finally, we observed
      that administration of lentiviral-miR-145 decreased the severity of ongoing,
      established EAMG with decreased IL-17 production, and also decreased serum anti
      AChR IgG levels. Our studies provide an important new insight into the
      pathogenesis of EAMG and MG, which may open a new perspective for the development
      of effective gene therapy for EAMG/MG. 

PMID- 24043549
TI  - A 24-hour approach to the study of health behaviors: temporal relationships
      between waking health behaviors and sleep.
AB  - BACKGROUND: Although sleep is often associated with waking health behaviors (WHB)
      such as alcohol consumption, caffeine use, smoking, and exercise, the causal
      direction of these relationships is unclear. PURPOSE: The present study used time
      series data to examine the temporal dynamics of WHB and sleep characteristics in
      participants of the Study of Women's Health Across the Nation Sleep Study.
      METHODS: Three hundred three women completed daily assessments of WHB and wore
      wrist actigraphs to measure sleep characteristics for the duration of the study
      (mean = 29.42 days, SD = 6.71). RESULTS: Vector autoregressive modeling revealed
      that weekly patterns of sleep and WHB best predicted subsequent sleep and WHB
      suggesting that the associations between WHB and sleep persist beyond their
      immediate influence. Some WHB predicted some subsequent sleep characteristics,
      but sleep did not predict subsequent WHB. CONCLUSIONS: These novel findings
      provide insight into the temporal dynamics of 24-h behaviors and encourage
      consideration of both sleep and WHB in health promotion and behavior change
      efforts.

PMID- 24043550
TI  - Late clinical presentation of congenital adrenal hyperplasia in older children:
      findings from national paediatric surveillance.
AB  - OBJECTIVES: To describe the clinical presentation and sequelae, including salt
      wasting crises of newly-diagnosed congenital adrenal hyperplasia (CAH) in
      children aged over 1 year in a contemporary population without screening. To
      appraise the potential benefit of newborn screening for late-presenting CAH.
      DESIGN: Active national surveillance undertaken in Great Britain prospectively
      from 2007-2009 through the British Paediatric Surveillance Unit. SETTING:
      England, Wales and Scotland. PATIENTS: Children first presenting aged 1-15 years
      with clinical features of CAH and elevated 17-hydroxyprogesterone. RESULTS: Fifty
      eight children (26 [45%] boys) aged 1-15 years were reported; 50 (86%) had 21
      hydroxylase deficiency. Diagnosis was precipitated by secondary sexual
      characteristics (n=38 [66%]; median age 5.8 [IQR] 4.8, 7.6) years, genital
      virilisation (8 girls; 3.2 [IQR 1.3, 7.3] years) or an affected sibling (n=8;
      10.0 [IQR 7.4, 13.3] years). At least 33 (57%) children had advanced bone age and
      13 (30%) were obese (body mass index >= 95 th centile). No child had experienced
      a salt-wasting crisis. CONCLUSIONS: In Great Britain, 30 children aged 1-15 years
      present annually for the first time with CAH. Older children frequently manifest
      prematurely advanced epiphyseal and pubertal maturation and genital virilisation,
      which are often irreversible and likely to have long-lasting consequences for
      adult health and wellbeing. Almost one-third of affected children are obese
      before commencing steroid therapy. Newborn screening offers the potential to
      avoid serious clinical manifestations in older children with unrecognised CAH;
      however, it may also detect some children who would otherwise remain asymptomatic
      and for whom the benefit from treatment is uncertain.

PMID- 24043552
TI  - Assessing efficient patient care: should length of stay be calculated
      independently of local admission rates?
AB  - OBJECTIVE: To compare the length of hospitalisation for infants with
      bronchiolitis across the Eastern region and to assess the impact of the varying
      admission rates in each hospital. DESIGN: Data collection through the Hospital
      Episode Statistics (HES) using the ICD clinical coding for bronchiolitis across
      all hospitals in east of England for three winter seasons (October to March for
      the years 2009/10, 2010/11 and 2011/12). MAIN OUTCOME MEASURE: Length of hospital
      stay, corrected to adjust for local population. RESULTS: Seventeen hospitals
      across the east of England were included in this study. Overall admission rate
      (as a percentage of the population) for the region was 3.3% and consistent with
      national data, but rates within individual hospitals varied between 1.5% and 5.7%
      over the 3-year period. Bed days per 1000 population ('standardised bed days')
      per year varied almost fourfold, from 34.5 to 122.3 in different hospitals.
      Corrected length of stay showed high discordance when compared to average length
      of stay. CONCLUSIONS: The average length of stay is substantially affected by
      admission rates, with hospitals who admit a greater proportion of infants
      appearing to have a shorter uncorrected length of stay. We propose that a single
      corrected measure for length of stay should be used when assessing the efficiency
      of care because it is unaffected by variations in local admission rates and is
      adjusted for local population size.

PMID- 24043551
TI  - Bruising in children who are assessed for suspected physical abuse.
AB  - OBJECTIVE: To describe the characteristics of bruising and mode of presentation
      of children referred to the paediatric child protection team with suspected
      physical abuse (PA), and the extent to which these differ between the children
      where abuse was confirmed and those where it was excluded. DESIGN: Cross
      sectional study. SETTING AND PATIENTS: 519 children, <6 years, referred to two
      paediatric child protection teams. MAIN OUTCOME MEASURES: The mode of
      presentation, number, anatomical distribution, size and appearance of bruises
      according to whether PA was confirmed or excluded. ORs with 95% CI were
      calculated where relevant. RESULTS: PA was confirmed in 69% of children; the rate
      varied from 84% when abuse was witnessed, admitted, alleged or where explanation
      for injury was absent or implausible, to 50% where there was a concerning
      history. Significantly more children with PA had bruises (89.4%) than PA-excluded
      (69.9%) and had significantly more sites affected (p<0.001). The odds of a PA
      child having bruising to: buttocks/genitalia (OR 10.9 (CI 2.6 to 46), left ear
      (OR 7.10 (CI 2.2 to 23.4), cheeks (Left (OR 5.20 (CI 2.5 to 10.7), Right OR 2.83
      (CI 1.5 to 5.4)), neck (OR 3.77 (CI 1.3 to 10.9), trunk (back (OR 2.85 (CI 1.6 to
      5.0) front (OR 4.74 (CI 2.2 to 10.2), front of thighs (OR2.48 (CI 1.4 to 4.5) or
      upper arms (OR 1.90 (CI 1.1 to 3.2) were significantly greater than in children
      with PA-excluded. Petechiae, linear or bruises with distinct pattern, bruises in
      clusters, additional injuries or a child known to social services for previous
      child abuse concerns were significantly more likely in PA. CONCLUSIONS: Features
      in the presenting history, the extent and pattern of bruising differed between
      children with confirmed PA and those where abuse was excluded. These findings can
      provide a deeper understanding of bruising sustained from PA.

PMID- 24043553
TI  - Skin blood flow influences cerebral oxygenation measured by near-infrared
      spectroscopy during dynamic exercise.
AB  - PURPOSE: Near-infrared spectroscopy (NIRS) is widely used to investigate cerebral
      oxygenation and/or neural activation during physiological conditions such as
      exercise. However, NIRS-determined cerebral oxygenated hemoglobin (O2Hb) may not
      necessarily correspond to intracranial blood flow during dynamic exercise. To
      determine the selectivity of NIRS to assess cerebral oxygenation and neural
      activation during exercise, we examined the influence of changes in forehead skin
      blood flow (SkBF(head)) on NIRS signals during dynamic exercise. METHODS: In ten
      healthy men (age: 20 +/- 1 years), middle cerebral artery blood flow velocity
      (MCA V mean, via transcranial Doppler ultrasonography), SkBF(head) (via laser
      Doppler flowmetry), and cerebral O2Hb (via NIRS) were continuously measured. Each
      subject performed 60 % maximum heart rate moderate-intensity steady-state cycling
      exercise. To manipulate SkBF(head), facial cooling using a mist of cold water (~4
      degrees C) was applied for 3 min during steady-state cycling. RESULTS: MCA V
      mean significantly increased during exercise and remained unchanged with facial
      cooling. O2Hb and SkBF(head) were also significantly increased during exercise;
      however, both of these signals were lowered with facial cooling and returned to
      pre-cooling values with the removal of facial cooling. The changes in O2Hb
      correlated significantly with the relative percent changes in SkBF(head) in each
      individual (r = 0.71-0.99). CONCLUSIONS: These findings suggest that during
      dynamic exercise NIRS-derived O2Hb signal can be influenced by thermoregulatory
      changes in SkBF(head) and therefore, may not be completely reflective of cerebral
      oxygenation or neural activation.

PMID- 24043555
TI  - [War and peace].

PMID- 24043554
TI  - A guide to oncological management of soft tissue tumours of the abdominal wall.
AB  - INTRODUCTION: An abdominal mass is a common clinical presentation, and a small
      percentage of such patients will have an abdominal wall tumour with the two most
      common pathologies being fibromatosis and soft tissue sarcoma. METHODS: Here we
      present the available literature on the diagnosis and management of both
      fibromatosis and soft tissue sarcoma, in the context of our experience in a
      tertiary referral centre for sarcoma. RESULTS AND DISCUSSION: Appropriate cross
      sectional imaging and a pre-operative tissue diagnosis by percutaneous core
      biopsy are necessary to define management. Desmoid fibromatosis can be managed
      initially by observation with serial imaging, with surgery being reserved for
      those patients who demonstrate progression. Soft tissue sarcoma can display a
      range of pathologies from relatively indolent tumours to locally aggressive
      sarcomas that can readily metastasise. An accurate pre-operative histological
      diagnosis and staging enables a multidisciplinary approach to management. This
      may include chemotherapy and radiotherapy, but the mainstay of treatment remains
      wide surgical resection and abdominal wall reconstruction. Patient outcomes are
      worse if referral is delayed or if the sarcoma is incompletely resected without
      an initial tissue diagnosis.

PMID- 24043556
TI  - Compliance with intermittent presumptive treatment and insecticide treated nets
      use during pregnancy in Enugu State, Nigeria.
AB  - To identify key socio-demographic and knowledge factors associated with
      compliance with recommended use of commodities for preventing malaria in
      pregnancy (MIP) in Enugu State, Nigeria. Cross-sectional study of 720 women who
      delivered within 6 months preceding the survey in three local government areas in
      Enugu State was conducted using a structured questionnaire. About half (51.6%) of
      the women used IPTp1 while 25.9% took IPTp2 as recommended during their most
      recent pregnancy. Forty-one percent of the women slept under insecticide treat
      nets (ITN) during the most recent pregnancy but only 15.4% did so as recommended
      every night. Socio-demographic and knowledge factors associated with compliance
      were identified. Compliance with intermittent presumptive treatment in pregnancy
      (IPTp) recommendation was more common among those in the rural setting (26.9%)
      compared to the peri-urban (20.3%) and urban (17.3%) (P = 0.032). Those with good
      knowledge of the causes, effects and prevention of malaria during pregnancy
      complied more (23.7%) than those with poor knowledge (17.0%) (P = 0.020). With
      respect to sleeping under ITN, more of those with post secondary education, good
      knowledge of MIP and currently living with a partner used ITN every night during
      the last pregnancy. Knowledge about the MIP issues and having a partner influence
      compliance with relevant preventives. Efforts to increase compliance with
      recommended practices to prevent MIP should focus on providing health education
      to pregnant women and their partners, who reinforce what the women are told
      during antenatal care. More qualitative studies need to be conducted on this
      subject.

PMID- 24043557
TI  - A community engagement process identifies environmental priorities to prevent
      early childhood obesity: the Children's Healthy Living (CHL) program for remote
      underserved populations in the US Affiliated Pacific Islands, Hawaii and Alaska.
AB  - Underserved minority populations in the US Affiliated Pacific Islands (USAPI),
      Hawaii, and Alaska display disproportionate rates of childhood obesity. The
      region's unique circumstance should be taken into account when designing obesity
      prevention interventions. The purpose of this paper is to (a), describe the
      community engagement process (CEP) used by the Children's Healthy Living (CHL)
      Program for remote underserved minority populations in the USAPI, Hawaii, and
      Alaska (b) report community-identified priorities for an environmental
      intervention addressing early childhood (ages 2-8 years) obesity, and (c) share
      lessons learned in the CEP. Four communities in each of five CHL jurisdictions
      (Alaska, American Samoa, Commonwealth of the Northern Mariana Islands, Guam,
      Hawai'i) were selected to participate in the community-randomized matched-pair
      trial. Over 900 community members including parents, teachers, and community
      leaders participated in the CEP over a 14 month period. The CEP was used to
      identify environmental intervention priorities to address six behavioral
      outcomes: increasing fruit/vegetable consumption, water intake, physical activity
      and sleep; and decreasing screen time and intake of sugar sweetened beverages.
      Community members were engaged through Local Advisory Committees, key informant
      interviews and participatory community meetings. Community-identified priorities
      centered on policy development; role modeling; enhancing access to healthy food,
      clean water, and physical activity venues; and healthy living education. Through
      the CEP, CHL identified culturally appropriate priorities for intervention that
      were also consistent with the literature on effective obesity prevention
      practices. Results of the CEP will guide the CHL intervention design and
      implementation. The CHL CEP may serve as a model for other underserved minority
      island populations.

PMID- 24043558
TI  - Understanding sociodemographic and sociocultural factors that characterize
      tobacco use and cessation during pregnancy among women in the Dominican Republic.
AB  - Tobacco use and exposure are serious public health problems that threaten to
      undermine improvements in maternal and child health, and add to already existing
      poor pregnancy outcomes in many low- and middle-income countries. The purpose of
      this study is to explore factors that characterize tobacco use and cessation
      during pregnancy among women in the Dominican Republic. This study was part of a
      larger trial and includes a sample of women who participated in baseline
      surveillance and community assessments (n = 613). Descriptive, bivariate, and
      multivariable analyses were conducted. Overall, 93.31 % (n = 572) of women
      experienced a past/current pregnancy and 22.44 % (n = 127) smoked during a past
      or current pregnancy. Among women who had smoked, 34.13 % (n = 43) stopped
      smoking due to a pregnancy, and 46.03 % (n = 58) were advised by a health care
      provider to quit smoking because of pregnancy. Women who were older, Catholic,
      and had a mother who used tobacco were three times more likely to smoke during a
      past or current pregnancy. Inability to read or write was also significantly
      associated with smoking during pregnancy. Women who were able to read and write
      and were from a tobacco growing community were three times more likely to quit
      smoking during pregnancy. This study provides a preliminary understanding of
      factors influencing tobacco use and cessation among pregnant women in the
      Dominican Republic. It also informs a critical area for public health research
      and intervention, indicating opportunities to engage the health care provider
      community in intervening with pregnant women and their families.

PMID- 24043560
TI  - Additive effects of parent adherence on social and behavioral outcomes of a
      collaborative school-home behavioral intervention for ADHD.
AB  - The present study evaluated the impact of the Collaborative Life Skills Program
      (CLS), a novel school-home psychosocial intervention, on social and behavioral
      impairments among children with attention and behavior problems. Fifty-seven
      ethnically/racially diverse children (70 % boys) with attention and/or behavior
      problems in the second through fifth grades participated in a pilot study. Ten
      school-based mental health professionals were trained and then implemented the
      intervention at their respective schools. Children significantly improved from
      pre- to post-treatment on parent, teacher, and report card ratings of children's
      social and behavioral functioning. Treatment improvements were consistent for
      children with and without co-occurring disruptive behavior problems. The impact
      of the intervention was enhanced when parents used the intervention strategies
      more regularly, according to both clinicians' and parents' reports. Findings
      support the emphasis of CLS on coordinating intervention strategies across
      contexts to facilitate the generalization of treatment-related improvements in
      social and behavioral functioning. 

PMID- 24043561
TI  - Measurement equivalence of the KINDL questionnaire across child self-reports and
      parent proxy-reports: a comparison between item response theory and ordinal
      logistic regression.
AB  - Measurement equivalence is a necessary assumption for meaningful comparison of
      pediatric quality of life rated by children and parents. In this study,
      differential item functioning (DIF) analysis is used to examine whether children
      and their parents respond consistently to the items in the KINDer
      Lebensqualitatsfragebogen (KINDL; in German, Children Quality of Life
      Questionnaire). Two DIF detection methods, graded response model (GRM) and
      ordinal logistic regression (OLR), were applied for comparability. The KINDL was
      completed by 1,086 school children and 1,061 of their parents. While the GRM
      revealed that 12 out of the 24 items were flagged with DIF, the OLR identified 14
      out of the 24 items with DIF. Seven items with DIF and five items without DIF
      were common across the two methods, yielding a total agreement rate of 50 %. This
      study revealed that parent proxy-reports cannot be used as a substitute for a
      child's ratings in the KINDL. 

PMID- 24043562
TI  - Using reduced rule base with Expert System for the diagnosis of disease in
      hypertension.
AB  - Hypertension, also called the "Silent Killer", is a dangerous and widespread
      disease that seriously threatens the health of individuals and communities
      worldwide, often leading to fatal outcomes such as heart attack, stroke, and
      renal failure. It affects approximately one billion people worldwide with
      increasing incidence. In Turkey, over 15 million people have hypertension. In
      this study, a new Medical Expert System (MES) procedure with reduced rule base
      was developed to determine hypertension. The aim was to determine the disease by
      taking all symptoms of hypertension into account in the Medical Expert System (7
      symptoms, 2(7) = 128 different conditions). In this new MES procedure, instead of
      checking all the symptoms, the reduced rule bases were used. In order to get the
      reduced rule bases, the method of two-level simplification of Boolean functions
      was used. Through the use of this method, instead of assessing 2(7) = 128
      individual conditions by taking 7 symptoms of hypertension into account, reduced
      cases were evaluated. The average rate of success was 97.6 % with the new MES
      procedure. 

PMID- 24043564
TI  - Amodal completion is modulated by lightness similarity.
AB  - The strength of amodal completion is known to be modulated by contour
      relationships and global shape. Some researchers have shown that amodal
      completion also depends on surface similarity, but they have not distinguished
      the relative importance of similarity in surface representations either pre or
      post lightness constancy. In the experiments reported here, we aimed to determine
      whether amodal completion depends on processes that occur either before or after
      the establishment of lightness constancy. We used computer rendering techniques
      to vary the consistency of a cast shadow with a decrement in luminance on one
      side of a partially occluded surface. We found that perceived completion depended
      on the consistency of the decrement in surface luminance with the orientation of
      a cast shadow (Exp. 1). In Experiment  2, we generated occluded surface fragments
      that could be either luminance-matched or lightness-matched to surface fragments
      on the opposite side of the occluder, and we found that the strength of amodal
      completion depended primarily on similarity in the perceived surface reflectance.
      In Experiments 3 and 4, we performed apparent-motion tasks to obtain converging
      evidence for grouping on the basis of perceived similarity in lightness. We found
      that matching surfaces in lightness significantly improved the apparent motion of
      surfaces behind an occluder, as compared with surfaces that were matched in
      contrast alone. These results suggest that amodal completion depends on the
      perceived similarity in lightness of partially occluded surface fragments. 

PMID- 24043565
TI  - Attentional engagement is not sufficient to prevent spatial capture.
AB  - What conditions, if any, can fully prevent attentional capture (i.e., involuntary
      allocation of spatial attention to an irrelevant object) has been a matter of
      debate. In a previous study, Folk, Ester, and Troemel (Psychonomic Bulletin &
      Review 16:127-132, 2009) suggested that attentional capture can be blocked
      entirely when attention is already engaged in a different object. This conclusion
      relied on the finding that in a search for a known-color target in a rapid serial
      visual presentation stream, a peripheral distractor with the target color did not
      further impair target identification performance when a distractor also with the
      target color that appeared in the stream had already captured attention. In the
      present study, we argue that this conclusion is unwarranted, because the effects
      of the central and peripheral distractors could not be disentangled. In order to
      isolate the effect of the peripheral distractor, we introduced a distractor
      target letter compatibility manipulation. Our results showed that the peripheral
      distractor summoned attention, irrespective of whether attention had just been
      engaged. We conclude that neither spatially focused attention nor attentional
      engagement is sufficient to prevent attentional capture. 

PMID- 24043563
TI  - Metastasis of ovarian cancer is mediated by kallikrein related peptidases.
AB  - Ovarian cancer, in particular epithelial ovarian cancer (EOC), is commonly
      diagnosed when the tumor has metastasized into the abdominal cavity with an
      accumulation of ascites fluid. Combining histopathology and genetic variations,
      EOC can be sub-grouped into Type-I and Type-II tumors, of which the latter are
      more aggressive and metastatic. Metastasis and chemoresistance are the key events
      associated with the tumor microenvironment that lead to a poor patient outcome.
      Kallikrein-related peptidases (KLKs) are aberrantly expressed in EOC, in
      particular, in the more metastatic Type-II tumors. KLKs are a family of 15 serine
      proteases that are expressed in diverse human tissues and involved in various
      patho-physiological processes. As extracellular enzymes, KLKs function in the
      hydrolysis of growth factors, proteases, cell membrane bound receptors, adhesion
      proteins, and cytokines initiating intracellular signaling pathways and their
      downstream events. High KLK levels are differentially associated with the
      prognosis of ovarian cancer patients, suggesting that they not only have
      application as biomarkers but also function in disease progression, and therefore
      are potential therapeutic targets. Recent studies have demonstrated the function
      of these proteases in promoting and/or suppressing the invasive behavior of
      ovarian cancer cells in metastasis in vitro and in vivo. Both conventional cell
      culture methods and three-dimensional platforms have been applied to mimic the
      ovarian cancer microenvironment of patients, such as the solid stromal matrix and
      ascites fluid. Here we summarize published studies to provide an overview of our
      understanding of the role of KLKs in EOC, and to lay the foundation for future
      research directions. 

PMID- 24043566
TI  - Is the emotional Stroop task a special case of mood induction? Evidence from
      sustained effects of attention under emotion.
AB  - Sustained effects of emotion are well known in everyday experience. Surprisingly,
      such effects are seldom recorded in laboratory studies of the emotional Stroop
      task, in which participants name the color of emotion and neutral words. Color
      performance is more sluggish with emotion words than with neutral words, the
      emotional Stroop effect (ESE). The ESE is not sensitive to the order in which the
      two groups of words are presented, so the effect of exposure to emotion words
      does not extend to disrupting performance in a subsequent block with neutral
      words. We attribute this absence of a sustained effect to habituation engendered
      by excessive repetition of the experimental stimuli. In a series of four
      experiments, we showed that sustained effects do occur when habituation is
      removed, and we also showed that the massive exposure to negative stimuli within
      the ESE paradigm induces a commensurately negative mood. A novel perspective is
      offered, in which the ESE is considered a special case of mood induction. 

PMID- 24043568
TI  - Interval examination: building primary care teams in an urban academic teaching
      clinic.

PMID- 24043567
TI  - A survey of U.S. physicians and their partners regarding the impact of work-home
      conflict.
AB  - BACKGROUND: Work-home conflicts (WHC) threaten work-life balance among
      physicians, especially those in dual career relationships. In this study, we
      analyzed factors associated with WHC for physicians and their employed partners.
      METHODS: We surveyed 89,831 physicians from all specialty disciplines listed in
      the Physician Masterfile. Of the 7,288 (27.7 %) physicians who completed the
      survey, 1,644 provided the e-mail contact information of their partner. We
      surveyed these partners and 891 (54 %) responded. Burnout, quality of life (QOL),
      and depression were measured using validated instruments in both surveys.
      Satisfaction with career, work-life balance, and personal relationships, as well
      as experience of WHC were also evaluated. RESULTS: WHC within the previous 3
      weeks were commonly experienced by physicians and their employed partners (44.3 %
      and 55.7 %, respectively). On multivariate analysis, greater work hours for
      physicians and their employed partners were independently associated with WHC (OR
      1.31 and 1.23 for each additional 10 h, respectively, both p < 0.0001).
      Physicians and partners who had experienced a recent WHC were more likely to have
      symptoms of burnout (47.1 % vs. 26.6 % for physicians with and without WHC; 42.4
      % vs. 23.8 % for partners with and without WHC, both p < 0.0001). CONCLUSIONS:
      WHC are commonly experienced by physicians and their employed partners. These
      conflicts may be a major contributor to personal distress for physicians and
      their partners.

PMID- 24043569
TI  - Maternal obesity induced by a high fat diet causes altered cellular development
      in fetal brains suggestive of a predisposition of offspring to neurological
      disorders in later life.
AB  - Fetal development in an obese maternal intrauterine environment has been shown to
      predispose the offspring for a number of metabolic disorders in later life. The
      observation that a large percentage of women of child-bearing age in the US are
      overweight/obese during pregnancy is therefore a source of concern. A high fat
      (HF) diet-induced obesity in female rats has been used as a model for maternal
      obesity. The objective of this study was to determine cellular development in
      brains of term fetuses of obese rats fed a HF diet from the time of weaning.
      Fetal brains were dissected out on gestational day 21 and processed for
      immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic
      regions. The major observation of this study is that fetal development in the
      obese HF female rat induced several alterations in the HF fetal brain. Marked
      increases were observed in orexigenic signaling and a significant decrease was
      observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF
      brains. Additionally, our results indicated diminished migration and maturation
      of stem-like cells in the 3rd ventricular region as well as in the brain cortex.
      The results from the present study indicate developmental alterations in the
      hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a
      predisposition for the development of obesity and possibly neurodevelopmental
      abnormalities in the offspring. 

PMID- 24043570
TI  - TRPM4 inhibition promotes angiogenesis after ischemic stroke.
AB  - Transient receptor potential melastatin 4 (TRPM4) is a voltage-dependent,
      nonselective cation channel. Under pathological conditions, sustained activation
      of TRPM4 leads to oncotic cell death. Here, we report the upregulation of TRPM4
      in vascular endothelium following hypoxia/ischemia in vitro and in vivo. In human
      umbilical vein endothelial cells, TRPM4 expression was increased at both the mRNA
      and protein levels following oxygen-glucose deprivation. Blocking TRPM4 with 9
      phenanthrol greatly enhanced tube formation on Matrigel. In a rat permanent
      middle cerebral artery occlusion model, TRPM4 was upregulated in the vascular
      endothelium within the penumbra region after stroke. TRPM4 expression peaked 1
      day post-occlusion and gradually decreased. In vivo siRNA-mediated TRPM4
      silencing enhanced angiogenesis and improved capillary integrity. A twofold
      reduction in infarct volume and a substantial recovery of motor function were
      observed in animals receiving the siRNA treatment. Interestingly, the protective
      effect of TRPM4 suppression disappeared 5 days after stroke induction, indicating
      that TRPM4 upregulation is critical for cerebral damage during the acute phase of
      stroke. TRPM4 could be a potential therapeutic target for ischemic stroke. 

PMID- 24043571
TI  - The principal conductance in Giardia lamblia trophozoites possesses functional
      properties similar to the mammalian ClC-2 current.
AB  - The human intestinal pathogen Giardia lamblia is a flagellated unicellular
      protozoan with pronounced medical and biological relevance. However, the basic
      physiology of Giardia trophozoites has been sparsely studied, especially the
      electrical and ionic properties of their cellular membrane which are virtually
      unknown. In this study, we were able to record and characterize the macroscopic
      ionic currents of Giardia trophozoite membrane by electrophysiological methods of
      the patch clamp technique. Giardia trophozoites showed a high current density
      (~600 pA/pF at -140 mV) that was activated upon hyperpolarization. This current
      was carried by a chloride-selective channel (I Cl-G) and it was the most
      important determinant of the membrane potential in Giardia trophozoites.
      Moreover, this conductance was able to carry other halide anions and the sequence
      of permeability was Br(-) > Cl(-) ~ I(-) ? F(-). Besides the voltage-dependent
      inward-rectifying nature of I Cl-G, its activation and deactivation kinetics were
      comparable to those observed in ClC-2 channels. Extracellular pH modified the
      voltage-dependent properties of I Cl-G, shifting the activation curve from a V
      1/2 = -79 +/- 1 mV (pH 7.4) to -93 +/- 2 mV (pH 8.4) and -112 +/- 2 mV (pH 5.4).
      Furthermore, the maximal amplitude of I Cl-G measured at -100 mV showed
      dependence to external pH in a bell-shaped fashion reported only for ClC-2
      channels. Therefore, our results suggest that I Cl-G possesses several functional
      properties similar to the mammalian ClC-2 channels.

PMID- 24043573
TI  - Different associations of adipokines in lean and healthy adults.
AB  - Regulation of adipokines in lean adults without metabolic disease and without
      eating disorders has not been comprehensively elucidated. We hypothesized that
      some of the established associations of these adipocyte-secreted proteins with
      anthropometric and biochemical measures of glucose homeostasis, lipid metabolism,
      renal function, as well as inflammation, differ in healthy and low weight adults
      as compared to overweight/obese patients. Eighty-one subjects with a body mass
      index below 22.0 kg/m2 and without malnutrition or eating disorders, as well as
      fifty overweight/obese patients, were recruited for the study. Serum
      concentrations of seven adipokines (adiponectin, leptin, adipocyte fatty acid
      binding protein [AFABP], chemerin, fibroblast growth factor [FGF]-21, resistin,
      retinol-binding protein [RBP]-4) were measured by enzyme-linked immunosorbent
      assays. Lean probands had significantly higher levels of adiponectin and
      resistin, as well as lower levels of leptin, AFABP, and RBP-4, as compared to
      overweight/obese subjects. Serum concentrations of adiponectin, leptin, AFABP,
      chemerin, and resistin were significantly higher in lean women as compared to men
      (p<0.05). In lean subjects, fasting insulin independently predicted leptin and
      resistin concentrations. Furthermore, C-reactive protein was independently
      associated with circulating AFABP and chemerin. Moreover, lean body mass was an
      independent predictor of leptin, fat mass predicted AFABP levels, whereas RBP-4
      was independently correlated to age and triglycerides. In addition, high density
      lipoprotein cholesterol predicted AFABP. Our results support the notion that
      several of these adipokines are regulated in a different manner in lean adults as
      compared to overweight/obese subjects and patients with eating disorders. 

PMID- 24043572
TI  - The many faces of T-type calcium channels.
AB  - Since the discovery of low-voltage-activated T-type calcium channels in sensory
      neurons and the initial characterization of their physiological function mainly
      in inferior olive and thalamic neurons, studies on neuronal T-type currents have
      predominantly focused on the generation of low-threshold spike (and associated
      action potential burst firing) which is strictly conditioned by a preceding
      hyperpolarization. This T-type current mediated activity has become an archetype
      of the function of these channels, constraining our view of the potential
      physiological and pathological roles that they may play in controlling the
      excitability of single cells and neural networks. However, greatly helped by the
      recent availability of the first potent and selective antagonists for this class
      of calcium channels, novel T-type current functions are rapidly being uncovered,
      including their surprising involvement in neuronal excitability at depolarized
      membrane potentials and their complex control of dendritic integration and
      neurotransmitter release. These and other data summarized in this short review
      clearly indicate a much wider physiological involvement of T-type channels in
      neuronal activity than previously expected. 

PMID- 24043574
TI  - Expression and cellular distribution of glucose transporters and alpha subunits
      of Na+/K+-ATPase in the heart of fructose-fed female rats: the role of estradiol.
AB  - Remarkable parallels are observed between glucose transporters (GLUT) and
      subunits of Na+/K+-ATPase, which deal with insulin regulation, tissue
      specificity, intracellular distribution and function of these proteins. To test
      our hypothesis that similarities also exist in alteration of cardiac GLUTs and
      alpha subunit isoforms of the pump in insulin resistance, animal model of
      fructose rich diet was exploited. The role of estradiol in regulation of GLUTs
      and Na+/K+-ATPase in insulin resistance context was studied as well. Cardiac
      protein expression, as well as insulin-regulated cellular localization of GLUT4,
      GLUT1, and alpha1 and alpha2 subunits of the pump were analyzed by Western blot.
      Fructose rich diet increased plasma insulin level and HOMA index, while estradiol
      treatment reversed both parameters to the control level. We did not observe
      obvious similarities in the pattern of alterations of GLUT1/alpha1 subunit of the
      pump, as well as GLUT4/alpha2 subunit, related to diet or hormone treatment.
      Considering alterations in expression and cellular localization of GLUTs and the
      pump subunits, fructose rich diet jeopardized cardiac glucose transport in some
      extent, but in contrast, stimulated Na+/K+-ATPase function. Estradiol treatment
      opposed the fructose diet biochemical action and the effect on cardiac GLUTs, but
      was inefficient concerning the changes of cardiac Na+/K+-ATPase subunits. Changes
      of the cardiac molecules can be mediated by alterations in the level of insulin
      and nonesterified fatty acids, induced by the diet and hormone treatment. 

PMID- 24043575
TI  - The genesis of empathy in human development: a phenomenological reconstruction.
AB  - In phenomenology, theories of empathy are intimately connected with the question
      of how it is possible to have insight into the mind of the other person. In this
      article, the author wants to show why it is self-evident for us that the other
      person is having experiences. In order to do so, it is not enough to discuss the
      phenomenon of empathy with a starting point in the already constituted adult
      person; instead the article presents a genetic approach to human development. The
      author thus contrasts Edith Stein's discussion of Einfuhlung (empathy), which
      takes its starting point in the experience of the grown-up, with Max Scheler's
      discussion of Einsfuhlung (feeling of oneness), where the relation between mother
      and infant is taken as one example. Maurice Merleau-Ponty's discussion of the
      world of the infant is read as one way of developing Scheler's theory of
      intersubjectivity and of Einsfuhlung. This genetic approach is developed further
      into a phenomenological analysis of the experience of the fetus and of birth. The
      author argues that the analysis of the fetus highlights the distinction between
      knowing that another person is having experiences, and knowing the specific
      content of the other person's experiences. The fetus does not experience
      different persons, but has a pre-subjective experience of life that includes what
      is later experienced as belonging to "another." Later in life, the experience of
      empathy, as an experience of a specific content, can be developed from this
      experience. In this way empathy and Einsfuhlung can be understood as
      complementary rather than as competing phenomena. 

PMID- 24043576
TI  - Expression of the high light-inducible Dunaliella LIP promoter in Chlamydomonas
      reinhardtii.
AB  - The development of highly inducible promoters is critical for designing effective
      transformation systems for transgenic analyses. In this study, we investigated
      the promoter of the light-inducible protein gene (LIP) of the marine alga
      Dunaliella sp. LIPs are homologs of the early light-induced proteins (ELIPs) of
      Arabidopsis thaliana. DNA sequence analysis revealed that the LIP promoter
      contains several light-responsive motifs. Constructs containing progressive
      truncations of the LIP promoter fused with a Renilla luciferase gene were
      introduced into Chlamydomonas reinhardtii to identify the light-responsive region
      in the promoter. Transcription from the LIP promoter was stimulated by high light
      (HL) in a light intensity-dependent manner. In contrast, oxidative stress induced
      by chemicals had little effect on the LIP promoter, which implies that the LIP
      promoter is exclusively induced by high light. Truncation of the promoter to a 
      100 base pair (bp) region abrogated light inducibility, which suggests the
      presence of a negative cis-regulatory element upstream of the -100 bp fragment.
      The LIP promoter can be utilized in transgenic research to specifically select
      and propagate transgenic microalgae under high-light conditions.

PMID- 24043577
TI  - Human umbilical cord-derived MSC culture: the replacement of animal sera with
      human cord blood plasma.
AB  - Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) hold great
      potential for their therapeutic use in various clinical diseases. Many
      publications have reported on human blood-derived alternatives to animal serum
      for culturing mesenchymal stem cells, such as human serum, allogenic umbilical
      cord blood serum, and human platelet derivatives. However, it is not clear
      whether human umbilical cord blood plasma (UCBP), as the surplusage of umbilical
      cord blood mesenchymal stem cell extraction, could be used. In this study, in
      order to make the best of umbilical cord blood, the human UCBP was dialyzed to
      replace fetal bovine serum (FBS) in the culture medium. hUC-MSCs were cultured in
      the new medium. Cell growth rate, specific biomarkers, and differentiation
      properties were detected to characterize the cell proliferation and MSC-specific
      properties. The hUC-MSCs cultured in such derived medium were verified with
      proliferation rate, cluster differentiation markers, cell cycle, as well as
      differentiation capabilities. Such dialyzed human UCBP is fully comparable with,
      if not superior to, FBS in deriving and culturing hUC-MSCs. 

PMID- 24043578
TI  - Safety and factors contributing to the difficulty of laparoscopic surgery for
      rectal cancer treated with preoperative chemoradiotherapy.
AB  - BACKGROUND: The safety of laparoscopic surgery for rectal cancer following
      chemoradiotherapy (CRT) has not been fully established. The aim of our
      retrospective study was to examine the outcomes and the factors contributing to
      the difficulty of laparoscopic surgery after CRT. METHODS: Eighty-seven
      consecutive rectal cancer patients treated with CRT were analyzed.
      Clinicopathological factors were compared between laparoscopic surgery (n = 57)
      and open surgery (n = 30) groups, and factors that correlated with operation time
      and blood loss were analyzed in low anterior resection (LAR) cases in the
      laparoscopic surgery group (n = 46). RESULTS: There was less blood loss in the
      laparoscopic surgery group than in the open surgery group (191 vs. 1,043 ml, p =
      0.0001), and the operation time in the two groups was similar (329 vs. 322 min, p
      = 0.8). The rate of conversion from laparoscopic surgery to open surgery was 1.8
      %. There was no significant difference in the morbidity rate (laparoscopic
      surgery 22.8 % vs. open surgery 33.3 %, p = 0.3). All circumferential resection
      margins were clear. Three-year cumulative rates of local recurrence were as
      follows: laparoscopic surgery: 1.9 % vs. open surgery: 8.4 % (p = 0.4), and
      distant recurrence was 28.5 % in laparoscopic surgery vs. 22.7 % in open surgery
      (p = 0.8) and these rates were not significantly different. In laparoscopic LAR
      cases, a shorter distance of the tumor from the anal verge was associated with a
      longer operation time. A high computed tomography Hounsfield units value of the
      mesorectum (CTV) was associated with increased blood loss in the first 23 cases,
      but not in the other 23 cases. CONCLUSIONS: Laparoscopic surgery following CRT
      was safe and feasible. A shorter anal verge was associated with a longer
      operation time. Blood loss increased in cases with high CTV, but this can likely
      be mitigated by experience.

PMID- 24043579
TI  - [Diagnostic principles for evaluation of retinal disorders. Part 1: functional
      analysis].

PMID- 24043580
TI  - The influences of guiding cues on motor skill autonomy in rats.
AB  - How does the effectiveness of guiding cues influence the development of motor
      skill autonomy? We utilized two sets of guiding cues (lights vs. reversed-lights
      conditions) that differed in their effectiveness to control a left-right
      leverpress sequence in rats. We separately measured the development of stimulus
      control by panel lights on guiding-cues trials and the development of stimulus
      control by practice cues on no-cue probe trials within the same sessions.
      Accuracy in the presence of the guiding cues was acquired faster in the lights
      condition than in the reversed-lights condition, but subjects in the reversed
      lights condition were more able to complete the skill autonomously than those in
      the lights condition. Throughout acquisition, control by guiding cues and
      practice cues developed at the same rate in the reversed-lights condition, but
      control by practice cues (autonomy) developed at a slower rate than did control
      by guiding cues in the lights condition. At the end of training, subjects that
      had been exposed to the reversed-lights condition displayed higher levels of
      autonomy than did those exposed to the lights condition. The less effective
      guiding cue (reversed-lights) produced greater levels of autonomy than did the
      more effective cue (lights), even though control by this guiding cue developed
      more slowly. Thus, guiding your child by the hand too much may reduce his or her
      ability to complete the task independently. We discuss the similarity to prompt
      dependence in children with learning disabilities and transfer of stimulus
      control. 

PMID- 24043581
TI  - Midsession reversals with pigeons: visual versus spatial discriminations and the
      intertrial interval.
AB  - Discrimination reversal learning has been used as a measure of species
      flexibility in dealing with changes in reinforcement contingency. In the
      simultaneous-discrimination, midsession-reversal task, one stimulus (S1) is
      correct for the first half of the session, and the other stimulus (S2) is correct
      for the second half. After training, pigeons show a curious pattern of choices:
      They begin to respond to S2 well before the reversal point (i.e., they make
      anticipatory errors), and they continue to respond to S1 well after the reversal
      (i.e., they make perseverative errors). That is, pigeons appear to be using the
      passage of time or the number of trials into the session as a cue to reverse, and
      are less sensitive to the feedback at the point of reversal. To determine whether
      the nature of the discrimination or a failure of memory for the stimulus chosen
      on the preceding trial contributed to the pigeons' less-than-optimal performance,
      we manipulated the nature of the discrimination (spatial or visual) and the
      duration of the intertrial interval (5.0 or 1.5 s), in order to determine the
      conditions under which pigeons would show efficient reversal learning. The major
      finding was that only when the discrimination was spatial and the intertrial
      interval was short did the pigeons perform optimally.

PMID- 24043582
TI  - Clinical outcomes of allogeneic stem cell transplantation for relapsed or
      refractory follicular lymphoma: a retrospective analysis by the Fukuoka Blood and
      Marrow Transplantation Group.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-SCT) is considered the
      only curative treatment for relapsed or refractory follicular lymphoma (FL), but
      it has a high treatment-related mortality rate. Only a few reports, however, have
      described the efficacy of allo-SCT for FL in the Japanese population. We
      retrospectively analyzed the outcome of allo-SCT in 30 patients with FL.
      Seventeen (56.7 %) patients were chemorefractory, whereas 13 (43.3 %) were
      chemosensitive. An estimated 2-year overall survival rate (OS) and relapse rate
      of all patients was 46.7 and 20.0 %, respectively. There were no significant
      differences in the estimated 2-year OS rate between patients who received
      myeloablative conditioning and those who received reduced-intensity conditioning
      (P = 0.98), and among the recipients of related bone marrow (BM)/peripheral blood
      stem cell, unrelated BM and umbilical cord blood (P = 0.20). In patients who were
      either chemosensitive or chemorefractory at allo-SCT, the 2-year OS rate was 69.2
      and 29.4 % (P = 0.06). Patients with mild-to-moderate acute GVHD had better 2
      year PFS rate compared with patients who had severe acute GVHD (P = 0.01), but
      not better PFS compared with patients who had no acute GVHD (P = 0.12). Our
      results suggest that the graft-versus-lymphoma effects of allo-SCT may provide
      survival benefits even in patients with chemorefractory FL.

PMID- 24043583
TI  - A tandem synthesis of functionalized azet-2(1H)-ones and azet-2(1H)-thiones.
AB  - Highly functionalized azet-2(1H)-ones and azet-2(1H)-thiones are obtained via a
      copper-catalyzed tandem reaction of readily available terminal alkynes, sulfonyl
      azides, and heterocummulenes in moderate to good yields.

PMID- 24043584
TI  - Synthesis of novel adamantyl and homoadamantyl-substituted beta-hydroxybutyric
      acids.
AB  - Several new adamantyl and homoadamantyl-substituted [Formula: see text]
      hydroxybutyric acids, 2-[2-(1-adamantyl)ethyl]-3-hydroxybutyric acid (2), 2-(3
      homoadamantyl)-3-hydroxybutyric acid (3), and 2-(1-homoadamantyl)-3
      hydroxybutyric acid (4), analogues of the 2-(1-adamantyl)-3-hydroxybutyric acid
      (1), have been prepared as mixtures of diastereoisomers using selective reduction
      of corresponding [Formula: see text]-keto esters or aldol condensation of the
      corresponding carboxylic acid and acetaldehyde. The rearrangement of
      adamantylmethyl and 3-homoadamantyl groups provided entry to both 3-homoadamantyl
      and 1-homoadamantyl-substituted hydroxy acids 3 and 4, respectively. The relative
      configurations of diastereoisomers 3 and 4 have been determined by NMR
      spectroscopy comparing the values of coupling constants. Adamantyl-substituted
      [Formula: see text]-hydroxybutyric acid 2 has also been prepared in
      enantiomerically pure form by Evan's asymmetric synthesis and the absolute
      configuration has been determined by X-ray crystallography. Contrary to the long
      chain acid 2, the attempt to prepare short-chain hydroxy acids 1 and 4 by the
      same method failed indicating pronounced sensitivity of the used method to the
      vicinity of the bulky cage group. 

PMID- 24043585
TI  - Separation of the fatty acids in menhaden oil as methyl esters with a highly
      polar ionic liquid gas chromatographic column and identification by time of
      flight mass spectrometry.
AB  - The fatty acids contained in marine oils or products are traditionally analyzed
      by gas chromatography using capillary columns coated with polyethylene glycol
      phases. Recent reports indicate that 100 % cyanopropyl siloxane phases should
      also be used when the analyzed samples contain trans fatty acids. We investigated
      the separation of the fatty acid methyl esters prepared from menhaden oil using
      the more polar SLB-IL111 (200 m * 0.25 mm) ionic liquid capillary column and the
      chromatographic conditions previously optimized for the separation of the complex
      mixture of fatty acid methyl esters prepared from milk fat. Identifications of
      fatty acids were achieved by applying Ag(+)-HPLC fractionation and GC-TOF/MS
      analysis in CI(+) mode with isobutane as the ionization reagent. Calculation of
      equivalent chain lengths confirmed the assignment of double bond positions. This
      methodology allowed the identification of 125 fatty acids in menhaden oil,
      including isoprenoid and furanoid fatty acids, and the novel 7-methyl-6
      hexadecenoic and 7-methyl-6-octadecenoic fatty acids. The chromatographic
      conditions applied in this study showed the potential of separating in a single
      90-min analysis, among others, the short chain and trans fatty acids contained in
      dairy products, and the polyunsaturated fatty acids contained in marine products.

PMID- 24043586
TI  - Changes of molecular glycerophospholipid species in plasma and red blood cells
      during docosahexaenoic acid supplementation.
AB  - Docosahexaenoic acid (DHA) status is related to health and disease risk. DHA
      status is mainly determined by dietary DHA intake, since endogenous synthesis of
      DHA is limited. We aimed to investigate the changes of different molecular
      glycerophospholipid species containing DHA in plasma and red blood cells (RBC) in
      response to increased DHA intake. Thirteen healthy adults had their diet
      supplemented with 510 mg DHA/day for 29 days. Fasted blood samples were taken at
      11 time points and glycerophospholipid species were analyzed by liquid
      chromatography mass spectrometry. In plasma, percentages of glycerophospholipid
      species containing DHA increased significantly by 64-104 % relative to baseline
      values during supplementation, but the relative distribution between species was
      not markedly altered. In RBC, phosphatidylcholine (PtdCho) species containing DHA
      increased to a similar extent as in plasma, while phosphatidylethanolamine and
      phosphatidylserine species with DHA increased by only 12-25 %, respectively,
      which was significantly different compared to PtdCho species (p < 0.01). Despite
      the high increase, the contribution of DHA PtdCho species to total DHA remained
      minor (14 % after supplementation). In conclusion, DHA supplementation does not
      alter the relative distribution of DHA among glycerophospholipid species in
      plasma. A majority of PtdCho species are rapidly exchanged between plasma
      lipoproteins and RBC membrane lipids, while there is a minor exchange of
      phosphatidylethanolamine and phosphatidylserine species.

PMID- 24043587
TI  - Common FABP4 genetic variants and plasma levels of fatty acid binding protein 4
      in older adults.
AB  - We examined common variants in the fatty acid binding protein 4 gene (FABP4) and
      plasma levels of FABP4 in adults aged 65 and older from the Cardiovascular Health
      Study. We genotyped rs16909187, rs1054135, rs16909192, rs10808846, rs7018409,
      rs2290201, and rs6992708 and measured circulating FABP4 levels among 3190
      European Americans and 660 African Americans. Among European Americans, the minor
      alleles of six single nucleotide polymorphisms (SNP) were associated with lower
      FABP4 levels (all p <= 0.01). Among African Americans, the SNP with the lowest
      minor allele frequency was associated with lower FABP4 levels (p = 0.015). The C
      A haplotype of rs16909192 and rs2290201 was associated with lower FABP4 levels in
      both European Americans (frequency = 16 %; p = 0.001) and African Americans
      (frequency = 8 %; p = 0.04). The haplotype combined a SNP in the first intron
      with one in the 3'untranslated region. However, the alleles associated with lower
      FABP4 levels were associated with higher fasting glucose in meta-analyses from
      the MAGIC consortium. These results demonstrate associations of common SNP and
      haplotypes in the FABP4 gene with lower plasma FABP4 but higher fasting glucose
      levels. 

PMID- 24043588
TI  - Assessing sensitivity and recovery of field-collected periphyton acutely exposed
      to atrazine using PSII inhibition under laboratory conditions.
AB  - Periphyton communities are an integral component of freshwater ecosystems and the
      desire to include data from toxicity testing with these organisms for ecological
      risk assessment is growing. This study developed sampling, storage, and exposure
      methods for the consistent and effective characterization of acute response and
      recovery of field-derived periphyton to photosystem II (PSII) inhibiting
      herbicides, particularly atrazine. Pulse amplitude modulated fluorometry was used
      to assess PSII quantum yield. For the method development phase, periphyton
      samples were collected from lotic and lentic systems in the Guelph, Ontario,
      Canada area during the summer of 2011. Following method development, native
      periphyton communities from three agricultural streams from the midwestern U.S.
      were sampled and exposed to atrazine (10-320 MUg/L) and assessed for inhibition
      of PSII quantum yield (from 2 up to 24 h) and subsequent recovery upon cessation
      of exposure (up to 48 h post-exposure). Sensitivity to atrazine (EC10 and EC50
      values) varied slightly (typically less than twofold difference) by site, date of
      sampling, and exposure interval. Only the highest initial test concentrations
      (160 or 320 MUg/L) demonstrated greater than ~5% inhibition at 48 h post
      exposure; however all other test concentrations recovered to within 5% of control
      levels, typically within 24 h. The rapid physiological recovery of periphyton
      communities upon atrazine removal supports the conclusion that acute exposure
      will not likely result in significant or sustained impacts on either structure or
      function of periphyton in lotic ecosystems. For ecological risk assessment, this
      suggests the current approach of relying on direct effects data for the most
      sensitive single species alone may result in overly conservative estimates of
      potential effects, especially for complex communities of primary producers.

PMID- 24043589
TI  - A new RNA-seq method to detect the transcription and non-coding RNA in prostate
      cancer.
AB  - Prostate cancer is a big killer in many regions especially American men, and this
      year, the diagnosed rate rises rapidly. We aimed to find the biomarker or any
      changing in prostate cancer patients. With the development of next generation
      sequencing, much genomic alteration has been found. Here, basing on the RNA-seq
      result of human prostate cancer tissue, we tried to find the transcription or non
      coding RNA expressed differentially between normal tissue and prostate cancer
      tissue. 10 T sample data is the RNA-seq data for prostate cancer tissue in this
      study, we found the differential gene is TFF3-Trefoil factor 3, which was more
      than seven fold change from prostate cancer tissue to normal tissue, and the most
      outstanding transcript is C15orf21. Additionally, 9 lncRNAs were found according
      our method. Finally, we found the many important non-coding RNA related to
      prostate cancer, some of them were long non-coding RNA (lncRNA). 

PMID- 24043590
TI  - Intestinal transport of 3,6'-disinapoylsucrose, a major active component of
      Polygala tenuifolia, using Caco-2 cell monolayer and in situ rat intestinal
      perfusion models.
AB  - 3,6'-Disinapoylsucrose is a major active component of the herb Polygala
      tenuifolia which has long been used for relieving tranquilization, uneasiness of
      the mind, and improving learning and memory. Our previous study found that 3,6'
      disinapoylsucrose had a very low oral bioavailability. Its mechanisms of
      absorption in the small intestine have so far been unclear. In the present study,
      the absorption mechanisms of 3,6'-disinapoylsucrose were investigated by using
      the Caco-2 cell monolayer and in situ rat intestinal perfusion models. The 3,6'
      disinapoylsucrose concentration was determined by an LC/MS/MS method. In a Caco-2
      cell transport study, the results showed that 3,6'-disinapoylsucrose had very
      limited intestinal permeability with average apparent permeability coefficient
      values around (1.11-1.34) * 10(-7) cm/s from the apical (A) to the basolateral
      (B) side and (1.37-1.42) * 10(-7) cm/s from B to A, at concentrations of 5, 20,
      and 33 uM. No concentration dependence in the 3,6'-disinapoylsucrose transport
      was observed. The apparent permeability coefficient value of 3,6'
      disinapoylsucrose (5 uM) from A to B greatly increased to 4.49 * 10(-7) and 1.81
      * 10(-7) cm/s, respectively, when the cells were preincubated with EDTA (17 mM)
      and sodium caprate (5.14 mM). No significant effect on the 3,6'-disinapoylsucrose
      transport by the inhibitors including verapamil, cyclosporine A, and sodium azide
      was observed. Similar results were found in the small intestinal perfusion study.
      The apparent permeability coefficient value of 3,6'-disinapoylsucrose greatly
      increased from 3.97 * 10(-6) to 23.4 * 10(-6) and 20.0 * 10(-6) cm/s in the
      presence of EDTA (17 mM) and sodium caprate (5.14 mM), respectively, in perfusion
      buffer. An in vitro stability evaluation of 3,6'-disinapoylsucrose in the
      gastrointestinal tract showed that it was relatively stable both in the stomach
      and small intestine contents, while it was found to be more instable in the colon
      contents. All of the above results indicate that 3,6'-disinapoylsucrose might be
      transported across the intestinal mucosa by paracellular passive penetration and
      paracellular enhancers could increase the intestinal permeability of this
      compound and thus slightly improve its oral bioavailability.

PMID- 24043591
TI  - Pharmacokinetics, tissue distribution, and excretion of salidroside in rats.
AB  - The present study investigated the pharmacokinetics, excretion, and tissue
      distribution of salidroside, a main active constituent in the roots of Rhodiola
      species. The plasma concentration declined rapidly following the intravenous
      dosing at 7.5, 15, and 30 mg/kg with a short half-life time of about 1 h. The
      mean values of area under the concentration-time curve (300.48 +/- 36.73, 514.51
      +/- 134.99, and 1036.64 +/- 101.67 mg . min/L), total body clearance (0.025 +/-
      0.003, 0.031 +/- 0.008, and 0.029 +/- 0.003 L/min/kg), and distribution value
      (2.02 +/- 0.80, 2.47 +/- 1.09 and 2.58 +/- 0.68 L/kg) suggested linear
      pharmacokinetics between the three doses. After intravenous injection of
      salidroside at 15 mg/kg, the total cumulative recovery of salidroside in urine
      was 53.67 +/- 12.03 % over 48 h, but only 0.09 +/- 0.03 % and 0.18 +/- 0.18 % of
      the dosage was excreted in bile and feces. Concentrations of salidroside in 12
      tissues as well as plasma were evaluated at 15, 40, and 120 min after dosing. At
      all time points, no higher concentration of salidroside was detected in tissues
      than that in plasma, with the lowest concentration of salidroside being observed
      in the brain, liver, fat, and skeletal muscle were tissues with a higher
      concentration of salidroside. A better distribution was also observed in the
      ovary and testis than that in the kidney and spleen. This finding demonstrated
      that salidroside is eliminated from plasma rapidly mainly by kidney clearance and
      conspicuously penetrated well into the skeletal muscle, fat, ovary and testis. A
      total recovered salidroside of about 54 % from excretion routes suggested that
      the metabolism was likely to take an important role in its elimination. 

PMID- 24043592
TI  - Computer-aided diagnosis of breast DCE-MRI images using bilateral asymmetry of
      contrast enhancement between two breasts.
AB  - Dynamic contrast material-enhanced magnetic resonance imaging (DCE-MRI) of
      breasts is an important imaging modality in breast cancer diagnosis with higher
      sensitivity but relatively lower specificity. The objective of this study is to
      investigate a new approach to help improve diagnostic performance of DCE-MRI
      examinations based on the automated detection and analysis of bilateral asymmetry
      of characteristic kinetic features between the left and right breast. An image
      dataset involving 130 DCE-MRI examinations was assembled and used in which 80
      were biopsy-proved malignant and 50 were benign. A computer-aided diagnosis (CAD)
      scheme was developed to segment breast areas depicted on each MR image, register
      images acquired from the sequential MR image scan series, compute average
      contrast enhancement of all pixels in one breast, and a set of kinetic features
      related to the difference of contrast enhancement between the left and right
      breast, and then use a multi-feature based Bayesian belief network to classify
      between malignant and benign cases. A leave-one-case-out validation method was
      applied to test CAD performance. The computed area under a receiver operating
      characteristic (ROC) curve is 0.78 +/- 0.04. The positive and negative predictive
      values are 0.77 and 0.64, respectively. The study indicates that bilateral
      asymmetry of kinetic features between the left and right breasts is a potentially
      useful image biomarker to enhance the detection of angiogenesis associated with
      malignancy. It also demonstrates the feasibility of applying a simple CAD
      approach to classify between malignant and benign DCE-MRI examinations based on
      this new image biomarker. 

PMID- 24043594
TI  - Computer-aided diagnosis for phase-contrast X-ray computed tomography:
      quantitative characterization of human patellar cartilage with high-dimensional
      geometric features.
AB  - Phase-contrast computed tomography (PCI-CT) has shown tremendous potential as an
      imaging modality for visualizing human cartilage with high spatial resolution.
      Previous studies have demonstrated the ability of PCI-CT to visualize (1)
      structural details of the human patellar cartilage matrix and (2) changes to
      chondrocyte organization induced by osteoarthritis. This study investigates the
      use of high-dimensional geometric features in characterizing such chondrocyte
      patterns in the presence or absence of osteoarthritic damage. Geometrical
      features derived from the scaling index method (SIM) and statistical features
      derived from gray-level co-occurrence matrices were extracted from 842 regions of
      interest (ROI) annotated on PCI-CT images of ex vivo human patellar cartilage
      specimens. These features were subsequently used in a machine learning task with
      support vector regression to classify ROIs as healthy or osteoarthritic;
      classification performance was evaluated using the area under the receiver
      operating characteristic curve (AUC). SIM-derived geometrical features exhibited
      the best classification performance (AUC, 0.95 +/- 0.06) and were most robust to
      changes in ROI size. These results suggest that such geometrical features can
      provide a detailed characterization of the chondrocyte organization in the
      cartilage matrix in an automated and non-subjective manner, while also enabling
      classification of cartilage as healthy or osteoarthritic with high accuracy. Such
      features could potentially serve as imaging markers for evaluating osteoarthritis
      progression and its response to different therapeutic intervention strategies. 

PMID- 24043593
TI  - Development of a software for quantitative evaluation radiotherapy target and
      organ-at-risk segmentation comparison.
AB  - Modern radiotherapy requires accurate region of interest (ROI) inputs for plan
      optimization and delivery. Target delineation, however, remains operator
      dependent and potentially serves as a major source of treatment delivery error.
      In order to optimize this critical, yet observer-driven process, a flexible web
      based platform for individual and cooperative target delineation analysis and
      instruction was developed in order to meet the following unmet needs: (1) an open
      source/open-access platform for automated/semiautomated quantitative
      interobserver and intraobserver ROI analysis and comparison, (2) a real-time
      interface for radiation oncology trainee online self-education in ROI definition,
      and (3) a source for pilot data to develop and validate quality metrics for
      institutional and cooperative group quality assurance efforts. The resultant
      software, Target Contour Testing/Instructional Computer Software (TaCTICS),
      developed using Ruby on Rails, has since been implemented and proven flexible,
      feasible, and useful in several distinct analytical and research applications. 

PMID- 24043595
TI  - The effect of discourse structure on depth of semantic integration in reading.
AB  - A coherent discourse exhibits certain structures in that subunits of discourses
      are related to one another in various ways and in that subunits that contribute
      to the same discourse purpose are joined to create a larger unit so as to produce
      an effect on the reader. To date, this crucial aspect of discourse has been
      largely neglected in the psycholinguistic literature. In two experiments, we
      examined whether semantic integration in discourse context was influenced by the
      difference of discourse structure. Readers read discourses in which the last
      sentence was locally congruent but either semantically congruent or incongruent
      when interpreted with the preceding sentence. Furthermore, the last sentence was
      either in the same discourse unit or not in the same discourse unit as the
      preceding sentence, depending on whether they shared the same discourse purpose.
      Results from self-paced reading (Experiment 1) and eye tracking (Experiment 2)
      showed that discourse-incongruous words were read longer than discourse-congruous
      words only when the critical sentence and the preceding sentence were in the same
      discourse unit, but not when they belonged to different discourse units. These
      results establish discourse structure as a new factor in semantic integration and
      suggest that discourse effects depend both on the content of what is being said
      and on the way that the contents are organized. 

PMID- 24043596
TI  - Characterization of intercostal muscle pathology in canine degenerative
      myelopathy: a disease model for amyotrophic lateral sclerosis.
AB  - Dogs homozygous for missense mutations in the SOD1 gene develop a late-onset
      neuromuscular disorder called degenerative myelopathy (DM) that has many
      similarities to amyotrophic lateral sclerosis (ALS). Both disorders are
      characterized by widespread progressive declines in motor functions, accompanied
      by atrophic changes in the descending spinal cord tracts. Some forms of ALS are
      also associated with SOD1 mutations. In end-stage ALS, death usually occurs as a
      result of respiratory failure from severe functional impairment of respiratory
      muscles. The mechanisms that lead to this loss of function are not known. Dogs
      with DM are euthanized at all stages of disease progression, providing an
      opportunity to characterize the onset and progression of any pathological changes
      in the respiratory muscles that may precede respiratory failure. To characterize
      such potential disease-related pathology, we evaluated intercostal muscles from
      Boxer and Pembroke Welsh Corgi dogs that were euthanized at various stages of DM
      disease progression. DM was found to result in intercostal muscle atrophy,
      fibrosis, increased variability in muscle fiber size and shape, and alteration in
      muscle fiber type composition. This pathology was not accompanied by retraction
      of the motor neuron terminals from the muscle acetylcholine receptor complexes,
      suggesting that the muscle atrophy did not result from physical denervation.
      These findings provide a better understanding of the mechanisms that likely lead
      to respiratory failure in at least some forms of ALS and will be useful in the
      development and evaluation of potential therapeutic interventions using the DM
      model.

PMID- 24043598
TI  - Lost in transition? Thoughts on retirement--"will you still need me, will you
      still feed me, when i'm sixty-four?".

PMID- 24043597
TI  - Effects of sulfonylureas on tumor growth: a review of the literature.
AB  - Type 2 diabetes mellitus patients are at higher cancer risk, probably because of
      hyperinsulinemia and insulin growth factor 1 pathway activation. The effects of
      antidiabetic drugs on cancer risk have been described and discussed in several
      studies suggesting opposite effects of the biguanide metformin and sulfonylureas
      on cancer incidence and mortality. The anticancer mechanisms of metformin have
      been clarified, and some clinical studies, particularly in breast cancer
      patients, have been published or are currently ongoing; however, data about the
      effects of sulfonylureas on cancer growth are less consistent. The aims of this
      work are to review preclinical evidence of second-generation sulfonylureas
      effects on tumor growth, to clarify the potential mechanisms of action, and to
      identify possible metabolic targets for patient selection. Most evidence is on
      the adenosine triphosphate-sensitive potassium channels inhibitor glibenclamide,
      which interacts with reactive oxygen species production thus inducing cancer cell
      death. Among diarylsulfonylureas, next-generation DW2282 derivatives are
      particularly promising because of the proapoptotic activity in multidrug
      resistant cells. 

PMID- 24043599
TI  - Changes in prevalence and clinical characteristics of cervical cancer in the
      People's Republic of China: a study of 10,012 cases from a nationwide working
      group.
AB  - PURPOSE: About one-third of the world's total annual new cervical cancer cases
      are found in the People's Republic of China. We investigate the prevalence and
      clinical characteristics of cervical cancer cases in the People's Republic of
      China over the past decade. METHOD: A total of 10,012 hospitalized patients with
      cervical cancer from regions nationwide were enrolled from 2000 to 2009.
      Demographic and clinical characteristics, therapeutic strategies, and outcomes
      were analyzed. RESULTS: The mean age at diagnosis of all cervical cancer patients
      was 44.7 +/- 9.5 years, which is 5-10 years younger than mean ages reported
      before 2000 in the People's Republic of China. The age distribution showed 16.0%
      of patients were <=35 years old, 41.7% were 35-45 years old, and 41.7% were >45
      years old. Early stage diagnoses were most prevalent: 57.3% were stage I, 33.9%
      were stage II, and 4.3% were stage III or IV. Most patients (83.9%) were treated
      with surgery, and only 9.5% had radiotherapy alone. Among 8,405 patients treated
      with surgery, 68.6% received adjuvant treatments, including chemotherapy (20.9%),
      radiotherapy (26.0%), and chemoradiotherapy (21.9%). Among stage IA patients,
      16.0% were treated with corpus uteri preservation. The proportion of ovarian
      preservation was 42.0%. CONCLUSIONS: Cervical cancer cases in the People's
      Republic of China show increasing prevalence in young patients and at early
      stages. In the past 10 years, surgery has become the dominant treatment and is
      increasingly combined with adjuvant chemotherapy for patients with stages I and
      II. Conservative surgical approaches are reasonable options for genital organ
      preservation in selected patients.

PMID- 24043600
TI  - Pinpointing moments of high anxiety during an MRI examination.
AB  - BACKGROUND: Magnetic Resonance Imaging (MRI) is associated with high levels of
      anxiety in many patients which may interfere with image quality and increase
      examination time. In order to develop effective intervention strategies that
      decrease anxiety, more insights into moments of high anxiety during a MRI
      examination are necessary. PURPOSE: The present study aimed at obtaining insights
      into anxiety levels and moments of high anxiety during a Magnetic Resonance
      Imaging examination. METHOD: The study included 67 patients, of whom 52 (77.6 %)
      were categorized as highly anxious. Stress and anxiety were measured continuously
      throughout the entire duration of the MRI examination by monitoring the heart
      rate. An increase in heart rate during the scan was taken as an indication for
      higher stress and anxiety. In addition to measuring stress and anxiety
      objectively, anxiety was assessed subjectively before and after the procedure by
      means of self-report questionnaires. RESULTS: The self-report data indicate that
      patients were highly anxious before the MRI examination. Moreover, the
      electrophysiological data clearly show that anxiety levels were highest at the
      beginning of the procedure, i.e., when the MRI table moved into the scanner, and
      then decreased over the course of the examination. Furthermore, the findings show
      that while subjectively measured anxiety was higher in patients who had taken
      anxiolytics prior to the MRI examination than in patients who had not taken any
      anxiolytics, objectively measured anxiety during the scan was equally high in
      both groups. CONCLUSION: The present study provides detailed insights into the
      anxiety levels during an MRI examination, which may aid in developing effective
      anxiety-reduction strategies. Additionally, the findings show that measuring
      anxiety continuously throughout the entire examination using electrophysiology in
      combination with measuring anxiety subjectively prior to and after the scan
      provides a more complete assessment of MRI-related anxiety.

PMID- 24043601
TI  - Giant cell tumors of the skull: a series of 18 cases and review of the
      literature.
AB  - Giant cell tumors (GCTs) are generally benign, locally aggressive lesions mostly
      located in the metaphysis of long bones. GCTs of the skull are rare and the
      majority of the cases have been presented as case reports. The authors
      retrospectively reported 18 patients with GCTs of the skull at a single
      institution from April 1994 to February 2012 and summarized the clinical,
      radiological, pathological characteristics and management of the disease.
      Meanwhile, a systematic review of 94 case reports of GCTs of the skull was
      performed. Headache and symptoms related to the involvement of intracranial
      nerves were the most common symptoms. Over 90 % of the tumors originated from
      sphenoid and temporal bones. On MRI, very low signal on T2-weighted images were
      found highly indicative of GCTs of the temporal bone. Univariate analysis
      revealed that extent of tumor resection and post-operative radiation therapy (RT)
      were prognostic factors significantly influencing the survival of the patients.
      We concluded that complete tumor resection is the optimal goal in treating this
      disease and adjuvant RT should be given once tumor residual is inevitable.

PMID- 24043602
TI  - Survival of breast cancer patients with meningeal carcinomatosis treated by
      intrathecal thiotepa.
AB  - Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal
      chemotherapy. Thiotepa is one of the few drugs approved in this setting, although
      no large cohort has been reported. The aim of our retrospective study is to
      describe survival and prognostic factors of breast cancer patients treated by
      intrathecal thiotepa. A search in the electronic database of the Institut Curie
      was performed and retrieved the patients diagnosed with breast cancer MC from
      2000 to 2012 and who received at least one intrathecal injection of thiotepa. The
      standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg),
      repeated every other week. Clinical data were retrieved from the computerized
      medical file of each patient. Sixty-six patients have been treated with
      intrathecal thiotepa either as first line or second line of treatment for breast
      cancer MC. The median overall survival was 4.5 months (range 0.1-50). There was
      no significant survival difference between patients treated as first or second
      line. In multivariate analysis, main adverse prognostic factors at diagnosis were
      performance status >2 (p = 0.001, RR = 3.4, 95 % CI 1.6-7.2) and history of more
      than 3 previous systemic chemotherapy lines (p = 0.002, RR = 2.90, 95 % CI 1.50
      5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21
      1 levels in the cerebrospinal fluid, and lack of clinical improvement were also
      independent adverse prognostic factors in multivariate analysis. This is the
      largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa
      ever reported. The median overall survival was short but some patients clearly
      benefited from this treatment, even used as second line.

PMID- 24043603
TI  - MicroRNA-9 inhibits vasculogenic mimicry of glioma cell lines by suppressing
      Stathmin expression.
AB  - The purpose of this study was to investigate the functions of microRNA-9, which
      is a tissue-specific microRNA in central nervous system, in the vasculogenic
      mimicry (VM) of glioma cell lines in vitro and in vivo. Glioma cell lines U87MG,
      U251 and SHG44 were transfected with microRNA-9 mimic, microRNA-9 inhibitor or
      scramble sequences. The amount of microRNA-9 and Stathmin (STMN1) mRNA was
      determined by quantitative real-time PCR, and the protein expression of STMN1 was
      determined by western blot. Cell proliferation and apoptosis were assessed. The
      interactions between the 3'UTR of STMN1 and miR-9 was determined by luciferase
      reporter assay. The VM capacity in vitro was evaluated using VM formation assay,
      and the rescue experiment of STMN1 was carried out in U251 cells. The in vivo
      experiment was applied with animal models implanted with U87MG cells.MicroRNA-9
      mimic transfection reduced proliferation and increased apoptosis in glioma cell
      lines (p < 0.05). MicroRNA-9 mimic up-regulated STMN1 mRNA levels but reduced its
      protein levels (p < 0.05), and luciferase activity of STMN1 was suppressed by
      microRNA-9 mimic transfection (p < 0.05). Furthermore, microRNA-9 mimic
      transfection suppressed tumor volume growth, as well as VM both in vitro and in
      vivo. The cell viability and microtube density were upregulated in U251 cells
      after STMN1 up-regulation (p < 0.05). STMN1 is a target of microRNA-9, and
      microRNA-9 could modulate cell proliferation, VM and tumor volume growth through
      controlling STMN1 expression. MicroRNA-9 and its targets may represent a novel
      panel of molecules for the development of glioma treatment.

PMID- 24043604
TI  - Characterization of the nutritional endoderm in the direct developing frog
      Eleutherodactylus coqui.
AB  - Unlike Xenopus laevis, Eleutherodactylus coqui develops without a tadpole. The
      yolk-rich vegetal region of the embryo forms a transient nutritive tissue, the
      nutritional endoderm (NE). The definitive endoderm (DE) in E. coqui comes from
      cells closer to the animal pole in contrast to its vegetal origin in X. laevis.
      RNA important for initiating the endoderm specification network is absent in
      presumptive NE cells, raising the question whether signaling occurs in them. We
      explored the nature of NE and asked how differences between NE and DE cells
      arise. We identified differences between NE and DE that first become evident at
      gastrula, when NE cells become multinucleated. Nuclear beta-catenin, an essential
      cofactor of sox 17, important for endoderm formation in X. laevis, is present in
      NE and DE at gastrula but remains in NE long after it is not seen in DE. We
      cloned E. coqui homologs of TGFbetas activin b and derriere and provide evidence
      for their maternal expression. We also detected activin b and derriere RNAs in NE
      at gastrula and show that NE possesses some mesoderm-inducing activity, but it is
      delayed with respect to DE. Our findings indicate that altered development of NE
      begins at gastrula. RNAs important for mesendoderm induction and some mesoderm
      inducing activity are present in NE. 

PMID- 24043606
TI  - Determining the impact of urban components on land surface temperature of
      Istanbul by using remote sensing indices.
AB  - For the past 60 years, Istanbul has been experiencing an accelerated urban
      expansion. This urban expansion is leading to the replacement of natural surfaces
      by various artificial materials. This situation has a critical impact on the
      environment due to the alteration of heat energy balance. In this study, the
      effect upon the urban heat island (UHI) of Istanbul was analyzed using 2009 dated
      Landsat 5 Thematic Mapper (TM) data. An Index Based Built-up Index (IBI) was used
      to derive artificial surfaces in the study area. To produce the IBI index, Soil
      Adjusted Vegetation Index, Normalized Difference Built-up Index, and Modified
      Normalized Difference Water Index were calculated. Land surface temperature (LST)
      distribution was derived from Landsat 5 TM images using a mono-window algorithm.
      In addition, 24 transects were selected, and different regression models were
      applied to explore the correlation between LST and IBI index. The results show
      that artificial surfaces have a positive exponential relationship with LST rather
      than a simple linear one. An ecological evaluation index of the region was
      calculated to explore the impact of both the vegetated land and the artificial
      surfaces on the UHI. Therefore, the quantitative relationship of urban components
      (artificial surfaces, vegetation, and water) and LST was examined using
      multivariate statistical analysis, and the correlation coefficient was obtained
      as 0.829. This suggested that the areas with a high rate of urbanization will
      accelerate the rise of LST and UHI in Istanbul. 

PMID- 24043607
TI  - Nitrogen enrichment in runoff sediments as affected by soil texture in Beijing
      mountain area.
AB  - Enrichment ratio (ER) is widely used in nonpoint source pollution models to
      estimate the nutrient loss associated with soil erosion. The objective of this
      study was to determine the ER of total nitrogen (ERN) in the sediments eroded
      from the typical soils with varying soil textures in Beijing mountain area. Each
      of the four soils was packed into a 40 by 30 by 15 cm soil pan and received 40
      min simulated rainfalls at the intensity of 90 mm h(-1) on five slopes. ERN for
      most sediments were above unity, indicating the common occurrence of nitrogen
      enrichment accompanied with soil erosion in Beijing mountain area. Soil texture
      was not the only factor that influenced N enrichment in this experiment since the
      ERN for the two fine-textured soils were not always lower. Soil properties such
      as soil structure might exert a more important influence in some circumstances.
      The selective erosion of clay particles was the main reason for N enrichment, as
      implied by the significant positive correlation between the ER of total nitrogen
      and clay fraction in eroded sediments. Significant regression equations between
      ERN and sediment yield were obtained for two pairs of soils, which were
      artificially categorized by soil texture. The one for fine-textured soils had
      greater intercept and more negative slope. Thus, the initially higher ERN would
      be lower than that for the other two soils with coarser texture once the sediment
      yield exceeded 629 kg ha(-1). 

PMID- 24043605
TI  - Biomechanics of atherosclerotic coronary plaque: site, stability and in vivo
      elasticity modeling.
AB  - Coronary atheroma develop in local sites that are widely variable among patients
      and are considerably variable in their vulnerability for rupture. This article
      summarizes studies conducted by our collaborative laboratories on predictive
      biomechanical modeling of coronary plaques. It aims to give insights into the
      role of biomechanics in the development and localization of atherosclerosis, the
      morphologic features that determine vulnerable plaque stability, and emerging in
      vivo imaging techniques that may detect and characterize vulnerable plaque.
      Composite biomechanical and hemodynamic factors that influence the actual site of
      development of plaques have been studied. Plaque vulnerability, in vivo, is more
      challenging to assess. Important steps have been made in defining the
      biomechanical factors that are predictive of plaque rupture and the likelihood of
      this occurring if characteristic features are known. A critical key in defining
      plaque vulnerability is the accurate quantification of both the morphology and
      the mechanical properties of the diseased arteries. Recently, an early IVUS based
      palpography technique developed to assess local strain, elasticity and mechanical
      instabilities has been successfully revisited and improved to account for complex
      plaque geometries. This is based on an initial best estimation of the plaque
      components' contours, allowing subsequent iteration for elastic modulus
      assessment as a basis for plaque stability determination. The improved method has
      also been preliminarily evaluated in patients with successful histologic
      correlation. Further clinical evaluation and refinement are on the horizon. 

PMID- 24043608
TI  - A successful treatment for concomitant injury of the coronary artery and
      tricuspid valve after blunt chest trauma.
AB  - A 63-year-old woman involved in an automobile accident was brought to our
      hospital with thoracic injury sustained by the impact of her vehicle's steering
      wheel. Cardiac auscultation revealed a grade III/VI systolic murmur and the
      electrocardiogram showed ST elevation in leads 2, 3 and aVF. A 2D echocardiogram
      revealed severe tricuspid regurgitation and a hypokinetic right ventricle.
      Coronary angiography revealed dissection of the proximal right coronary artery
      (RCA) with 90 % stenosis. Urgent CABG for the RCA and tricuspid valvuloplasty
      were performed, as the anterior leaflet of the tricuspid valve had prolapsed as a
      result of chordal rupture. Blunt thoracic trauma causing both tricuspid
      insufficiency and coronary artery dissection is a very rare and life-threatening
      situation. Prompt diagnosis and timely surgery enabled us to save this patient's
      life.

PMID- 24043609
TI  - Lumbar plexus injury in an anterior fracture dislocation of sacroiliac joint: a
      case report and review of literature.
AB  - Displaced unstable pelvic fractures are commonly associated with disruption of
      the osteoarticular junction of the sacroiliac joint. Posterior sacroiliac
      dislocation are commonly reported but there are only few reports the anterior
      type of sacroiliac dislocation where the iliac bone fractures and displaces
      anterior to sacrum, often in combination with fractures of pubic rami and
      symphyseal injuries. We present a case of an anterior type of sacroiliac fracture
      dislocation which was associated with a lumbar plexus injury involving both motor
      and sensory components. Preoperative neurological assessment was done by MRI
      scan. The tented nerve roots were explored and decompressed surgically, and
      sacroiliac fixation was done after reduction in the fracture and joint. 

PMID- 24043610
TI  - Perturbation analysis of indices of lifespan variability.
AB  - A number of indices exist to calculate lifespan variation, each with different
      underlying properties. Here, we present new formulae for the response of seven of
      these indices to changes in the underlying mortality schedule (life disparity,
      Gini coefficient, standard deviation, variance, Theil's index, mean logarithmic
      deviation, and interquartile range). We derive each of these indices from an
      absorbing Markov chain formulation of the life table, and use matrix calculus to
      obtain the sensitivity and the elasticity (i.e., the proportional sensitivity) to
      changes in age-specific mortality. Using empirical French and Russian male data,
      we compare the underlying sensitivities to mortality change under different
      mortality regimes to determine the conditions under which the indices might
      differ in their conclusions about the magnitude of lifespan variation. Finally,
      we demonstrate how the sensitivities can be used to decompose temporal changes in
      the indices into contributions of age-specific mortality changes. The result is
      an easily computable method for calculating the properties of this important
      class of longevity indices. 

PMID- 24043611
TI  - Identification and distribution of Puroindoline b-2 variant gene homologs in
      Hordeum.
AB  - The barley hordoindoline genes (Hina and Hinb) are homologous to the wheat
      puroindoline genes (Pina and Pinb). These genes are involved in grain hardness,
      which is an important quality for barley processing. We identified novel variants
      of Hina and Hinb in 10 wild Hordeum species (H. bogdanii, H. brachyantherum, H.
      bulbosum, H. chilense, H. comosum, H. marinum, H. murinum, H. patagonicum, H.
      pusillum, and H. roshevitzii) covering all Hordeum genomes and preliminarily
      named them Hinc. These nucleotide sequences were highly similar to those of
      Puroindoline b-2 variant genes (Pinb-2v) and were located on chromosome 7I in H.
      chilense. The Hinc genes in H. bogdanii, H. bulbosum, H. patagonicum, and H.
      roshevitzii were pseudogenes possessing in-frame stop codons. We also found a
      partial Hinc sequence in H. murinum. This gene was not found in cultivated barley
      and H. vulgare subsp. spontaneum. The phylogenetic tree of Gsp-1, Hin, and Pin
      genes demonstrates that Hinc and Pinb-2v genes formed one cluster. Therefore, we
      considered that Hinc and Pinb-2v genes shared a common ancestral gene and were
      homologous to each other. We also studied the evolutional process of Gsp-1, Hin,
      and Pin genes. Our results suggested that Gsp-1 might be the most closely related
      to a putative ancestral gene on Ha locus.

PMID- 24043612
TI  - Pediatric patients with Marfan syndrome: frequency of dural ectasia and its
      correlation with common cardiovascular manifestations.
AB  - PURPOSE: Marfan syndrome (MFS) is a genetic disorder of the connective tissue.
      Aortic root dilation is a main criterion of the Ghent Nosology. Dural ectasia and
      the presence of mitral valve prolapse (MVP) contribute to its systemic score. The
      purpose of this study was to investigate the frequency of dural ectasia and its
      correlation with cardiovascular manifestations in a pediatric study population.
      PATIENTS AND METHODS: 119 pediatric patients with confirmed or suspected MFS were
      examined in the local Marfan Clinic. 31 children with MFS who underwent magnetic
      resonance imaging (MRI) were included. Each patient was evaluated according to
      the Ghent nosology. Echocardiography was used to measure the aortic root diameter
      and assess the presence of MVP and mitral regurgitation. Z-scores were calculated
      for the evaluation of the aortic root diameters. MRI was performed to determine
      the dural sac ratio (DSR). RESULTS: The prevalence of dural ectasia was 90.3 %,
      of aortic root dilation 32.2 %, of MVP 64.5 % and of mitral regurgitation 51.6 %.
      DSR at L5 correlated with the intraindividual z-scores (slope, 3.62 +/- 1.5
      [0.56; 6.68]; r = 0.17; p = 0.02; F = 5.84). Z-scores >= 2 were accompanied by
      dural ectasia in 100 %, MVP in 95 % and mitral regurgitation in 100 % of cases.
      MVP was accompanied by mitral regurgitation in 70 % of cases. CONCLUSION: As the
      examined cardiac manifestations show a coincidence with dural ectasia in 95 - 100
      % of cases, MRI for diagnostic dural sac imaging should be reserved for MFS
      suspicions with the absence of those manifestations in order to establish the
      diagnosis according to the Ghent criteria. Thus, the present study supports the
      recent downgrading of dural ectasia to a contributor to the systemic score.

PMID- 24043613
TI  - Value of digital radiography in expiration in detection of pneumothorax.
AB  - PURPOSE: The purpose of this study was to find out whether pneumothorax detection
      and exclusion is superior in expiratory digital chest radiography. MATERIALS AND
      METHODS: 131 patients with pneumothorax with paired inspiratory and expiratory
      chest radiographs were analyzed regarding localization and size of pneumothorax.
      Sensitivity, specificity, negative (npv) and positive predictive value (ppv) as
      well as the positive (LR+) and negative likelihood ratio (LR-) were determined in
      a blinded randomized interobserver study with 116 patients. The evaluation was
      performed by three board-certified radiologists. RESULTS: In 131 patients, there
      were 139 pneumothoraces, 135 (97.1 %) were located apical, 88 (63.3 %) lateral
      and 33 (23.7 %) basal. Sensitivity was 99 % for inspiratory and 97 % for
      expiratory radiographs. The interobserver study yielded a mean sensitivity of
      86.1 %/86.1 %, specificity of 97.3 %/93.4 %, npv of 88.7 %/88.5 % and ppv of 96.7
      %/92.1 % for inspiration/expiration. For inspiratory radiographs the LR+/LR- were
      40.2/0.14 and for expiration 13.9 and 0.15. McNemar-Test showed no significant
      difference for the detection of pneumothoraces in in-/exspiration. CONCLUSION:
      Inspiratory and expiratory digital radiographs are equally suitable for
      pneumothorax detection. Inspiratory radiographs are recommended as the initial
      examination of choice for pneumothorax detection, an additional expiratory
      radiograph is only recommended in doubtful cases. KEY POINTS: * Basal
      pneumothoraces during inspiration demonstrate a greater width than during
      expiration. * There is statistically no difference between inspiration/expiration
      for the diagnosis of pneumothorax. * An image taken during inspiration is
      recommended to confirm or rule out a pneumothorax.

PMID- 24043614
TI  - Development of free-living stages of Strongyloides ratti under different
      temperature conditions.
AB  - It is well known that the Strongyloides species have two different developmental
      courses-direct and indirect development-and selection of these courses is
      affected by various environmental factors. This study examined the effect of
      temperature on the development of first-stage larvae (L1s) of Strongyloides
      ratti, to clarify how larvae adapt and survive at unsuitable temperatures. It was
      revealed that L1s cultured at 4 or 10  degrees C for 120 h could not develop
      because of growth arrest or delay. However, L1s could develop after transfer to
      culture at 25  degrees C for 48 h. Although larvae cultured at 25  degrees C take
      indirect development, larvae subjected to low-temperature stimulation (at 4 or 10
      degrees C) take direct development into infective third-stage larvae (L3s), and
      only 1 min of low-temperature stimulation was sufficient to induce direct
      development. Morphological study of low-temperature-stimulated L3s revealed that
      those stimulated at 4  degrees C (L3-4) showed less development, but those
      stimulated at 10  degrees C (L3-10) developed as well as the control (no low
      temperature stimulation). Furthermore, we revealed that L3-10 showed similar
      infectivity to the control when they were injected subcutaneously into rats as
      the final host, which indicated that L3-10 grew normally. We conclude that S.
      ratti has a survival strategy of growth arrest or delay if excreted in cold
      conditions. Moreover, even if they start development after transfer to suitable
      conditions, they memorize low-temperature stimulation, which leads them to direct
      development thereafter so that they can immediately infect the final host. 

PMID- 24043615
TI  - Ultrastructural characteristics of the vaginae of the basal monogenean
      Chimaericola leptogaster (Leuckart, 1830).
AB  - In the first study of the vaginal ultrastructure of any monogenean, the paired
      vaginae of Chimaericola leptogaster, a basal polyopisthocotylean from the gills
      of a holocephalan, are described. Each vagina opens laterally. A unique feature
      of this relict parasite is a short vagino-intestinal connecting duct, the lining
      of which is separated by septate junctions from the linings of the vagina and the
      intestine. After giving rise to this vagino-intestinal duct, each vagina travels
      in a posterior direction and opens into the vitelline collecting duct. The lining
      of each vagina close to the vaginal pore resembles the body tegument, the
      syncytial lining of which measures about 2.5 MUm in thickness and has a dense
      surface layer 0.2 MUm in thickness and different apical projections. Proximal to
      this and before the entrance to the vaginal-intestinal duct, the vaginal lining
      is characterised by: uniformly distributed electron-dense, lanceolate, spine-like
      surface structures of about 1.7 MUm in length; three kinds of surrounding glands
      with three kinds of secretory granules (abundant oval or rounded electron-dense
      granules 0.7-2.5 MUm in length, much less numerous spheroidal, vesicular granules
      0.3-0.4 MUm in diameter, and tightly packed, spheroidal granules 0.8 MUm in
      diameter and containing fine particulate material of low density); and four kinds
      of sensory receptors (three uniciliate and one aciliate). These features are
      absent from the rest of the vagina. The likely roles of the vagino-intestinal
      connection, the different gland cells, sensory structures, and the armament of
      the distal vaginal regions are discussed. Considering the suggested
      polyopisthocotylean ancestor for the Neodermata, the relict parasite fauna of
      holocephalans and the unique vagino-intestinal connection in C. leptogaster,
      which is also known in turbellarians, an ancient origin for chimaericolids is
      supported. 

PMID- 24043616
TI  - MRI of the foetal brain using a rapid 3D steady-state sequence.
AB  - OBJECTIVE: To evaluate the capacity of a rapid T2 weighted three-dimensional (3D)
      sequence to diagnose foetal brain abnormalities by comparing the results with
      current two-dimensional (2D) methods. We have also made assessments of the
      estimates of energy deposition using those methods. METHODS: 50 pregnant females
      were included in this study under the guidance of the institutional review board.
      All their foetuses had suspected brain abnormalities on antenatal ultrasonography
      or were at increased risk of a brain malformation based on the results of an
      earlier pregnancy. All the foetuses had a routine MR protocol that includes three
      orthogonal plane single-shot fast-spin echoes and 2D steady-state sequences. In
      addition, a 3D rapid steady-state sequence of the foetal brain was performed
      (acquisition time approximately 40 s), and the standard and 3D sequences were
      reported independently and the results were compared. The specific absorption
      rate (SAR) predicted by the scanner was recorded in 12 cases in order to estimate
      the energy deposited by the three sequences. RESULTS: The 3D rapid steady-state
      sequences produced diagnostic-quality images in 41/50 (82%) cases. All the
      failures were in second trimester foetuses (9/26-35% failure rate). There was a
      discrepancy between the standard report and findings using the 3D sequence in
      2/41 of the foetuses with good-quality 3D imaging. The predicted SAR deposition
      of the 3D steady-state sequences was comparable with the single-shot fast-spin
      echo sequence. CONCLUSION: Our initial assessments of a 3D rapid steady-state
      sequence to image the foetus are encouraging in terms of diagnostic information
      and acceptable energy deposition values. The high failure rate in second
      trimester foetuses probably relates to the greater mobility of the smaller
      foetuses, and improvements in the 3D sequence are required in terms of reduced
      acquisition time and higher resolution. ADVANCES IN KNOWLEDGE: We have shown that
      3D T2 weighted images of the foetal brain can be acquired in a clinical setting
      and produce diagnostic-quality imaging in a high proportion of cases. The success
      rate in acquiring diagnostic-quality images is related to gestational age. Good
      quality images were obtained in all third trimester foetuses but only in
      approximately two-thirds of second trimester foetuses. This probably reflects the
      problem of the greater mobility of second trimester foetuses. 3D T2 weighted
      acquisitions have great potential for improving the antenatal diagnosis of foetal
      brain abnormalities and may reduce the time that a pregnant female needs to spend
      on the MR scanner.

PMID- 24043617
TI  - Characterization of the nucleoid-associated protein YejK.
AB  - Nucleoid-associated proteins play an important role in condensing chromosomal DNA
      and regulating gene expression. We report here the characterization of the
      nucleoid-associated protein YejK, which was detected in a yeast two-hybrid screen
      using the ParE subunit of topoisomerase IV as bait. The purified protein likely
      exists in a monomer-dimer equilibrium in solution and can form tetramers. Cross
      linking of the protein bound to DNA suggests that the active form could be either
      a dimer or tetramer. YejK, which is present at about 24,000 copies of monomer per
      mid-log phase cell, binds double-stranded DNA with a site size of 12-14 base
      pairs/monomer, does not display a significant preference for either bent compared
      with straight DNA or supercoiled compared with relaxed DNA, and untwists DNA
      somewhat as it binds. YejK binds RNA, but not single-stranded DNA, with 65% of
      the avidity with which it binds DNA. However, cells deleted for yejK do not show
      defects in either RNA or protein synthesis. YejK interacts with all the subunits
      of both DNA gyrase and topoisomerase IV and has measurable effects on their
      activities. In the presence of YejK, relaxation of negatively supercoiled DNA by
      topoisomerase IV becomes distributive, whereas relaxation of positively
      supercoiled DNA is stimulated. Relaxation of negatively supercoiled DNA by DNA
      gyrase is inhibited, whereas the extent of supercoiling of relaxed DNA is
      limited. A YejK-GFP chimera is an effective marker for the nucleoid in live cell
      imaging. 

PMID- 24043618
TI  - Analysis of the activities of RAD54, a SWI2/SNF2 protein, using a specific small
      molecule inhibitor.
AB  - RAD54, an important homologous recombination protein, is a member of the
      SWI2/SNF2 family of ATPase-dependent DNA translocases. In vitro, RAD54 stimulates
      RAD51-mediated DNA strand exchange and promotes branch migration of Holliday
      junctions. It is thought that an ATPase-dependent DNA translocation is required
      for both of these RAD54 activities. Here we identified, by high-throughput
      screening, a specific RAD54 inhibitor, streptonigrin (SN), and used it to
      investigate the mechanisms of RAD54 activities. We found that SN specifically
      targets the RAD54 ATPase, but not DNA binding, through direct interaction with
      RAD54 and generation of reactive oxygen species. Consistent with the dependence
      of branch migration (BM) on the ATPase-dependent DNA translocation of RAD54, SN
      inhibited RAD54 BM. Surprisingly, the ability of RAD54 to stimulate RAD51 DNA
      strand exchange was not significantly affected by SN, indicating a relatively
      smaller role of RAD54 DNA translocation in this process. Thus, the use of SN
      enabled us to identify important differences in the effect of the RAD54 ATPase
      and DNA translocation on two major activities of RAD54, BM of Holliday junctions
      and stimulation of DNA pairing. 

PMID- 24043619
TI  - N-terminal serine dephosphorylation is required for KCC3 cotransporter full
      activation by cell swelling.
AB  - The K(+):Cl(-) cotransporter (KCC) activity is modulated by
      phosphorylation/dephosphorylation processes. In isotonic conditions, KCCs are
      inactive and phosphorylated, whereas hypotonicity promotes their
      dephosphorylation and activation. Two phosphorylation sites (Thr-991 and Thr
      1048) in KCC3 have been found to be critical for its regulation. However, here we
      show that the double mutant KCC3-T991A/T1048A could be further activated by
      hypotonicity, suggesting that additional phosphorylation site(s) are involved. We
      observed that in vitro activated STE20/SPS1-related proline/alanine-rich kinase
      (SPAK) complexed to its regulatory MO25 subunit phosphorylated KCC3 at Ser-96 and
      that in Xenopus laevis oocytes Ser-96 of human KCC3 is phosphorylated in isotonic
      conditions and becomes dephosphorylated during incubation in hypotonicity,
      leading to a dramatic increase in KCC3 function. Additionally, WNK3, which
      inhibits the activity of KCC3, promoted phosphorylation of Ser-96 as well as Thr
      991 and Thr-1048. These observations were corroborated in HEK293 cells stably
      transfected with WNK3. Mutation of Ser-96 alone (KCC3-S96A) had no effect on the
      activity of the cotransporter when compared with wild type KCC3. However, when
      compared with the double mutant KCC3-T991A/T1048A, the triple mutant KCC3
      S96A/T991A/T1048A activity in isotonic conditions was significantly higher, and
      it was not further increased by hypotonicity or inhibited by WNK3. We conclude
      that serine residue 96 of human KCC3 is a third site that has to be
      dephosphorylated for full activation of the cotransporter during hypotonicity. 

PMID- 24043620
TI  - Identification of a Plasmodium falciparum phospholipid transfer protein.
AB  - Infection of erythrocytes by the human malaria parasite Plasmodium falciparum
      results in dramatic modifications to the host cell, including changes to its
      antigenic and transport properties and the de novo formation of membranous
      compartments within the erythrocyte cytosol. These parasite-induced structures
      are implicated in the transport of nutrients, metabolic products, and parasite
      proteins, as well as in parasite virulence. However, very few of the parasite
      effector proteins that underlie remodeling of the host erythrocyte are
      functionally characterized. Using bioinformatic examination and modeling, we have
      found that the exported P. falciparum protein PFA0210c belongs to the START
      domain family, members of which mediate transfer of phospholipids, ceramide, or
      fatty acids between membranes. In vitro phospholipid transfer assays using
      recombinant PFA0210 confirmed that it can transfer phosphatidylcholine,
      phosphatidylinositol, phosphatidylethanolamine, and sphingomyelin between
      phospholipid vesicles. Furthermore, assays using HL60 cells containing
      radiolabeled phospholipids indicated that orthologs of PFA0210c can also transfer
      phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine.
      Biochemical and immunochemical analysis showed that PFA0210c associates with
      membranes in infected erythrocytes at mature stages of intracellular parasite
      growth. Localization studies in live parasites revealed that the protein is
      present in the parasitophorous vacuole during growth and is later recruited to
      organelles in the parasite. Together these data suggest that PFA0210c plays a
      role in the formation of the membranous structures and nutrient phospholipid
      transfer in the malaria-parasitized erythrocyte. 

PMID- 24043622
TI  - Circular permutation directs orthogonal assembly in complex collagen peptide
      mixtures.
AB  - Multiple types of natural collagens specifically assemble and co-exist in the
      extracellular matrix. Although noncollagenous trimerization domains facilitate
      the folding of triple-helical regions, it is intriguing to ask whether collagen
      sequences are also capable of controlling heterospecific association. In this
      study, we designed a model system mimicking simultaneous specific assembly of two
      collagen heterotrimers using a genetically inspired operation, circular
      permutation. Previously, surface charge-pair interactions were optimized on three
      collagen peptides to promote the formation of an abc-type heterotrimer. Circular
      permutation of these sequences retained networks of stabilizing interactions,
      preserving both triple-helical structure and heterospecificity of assembly.
      Combining original peptides A, B, and C and permuted peptides D, E, and F
      resulted primarily in formation of A:B:C and D:E:F, a heterospecificity of 2 of
      56 possible stoichiometries. This degree of specificity in collagen molecular
      recognition is unprecedented in natural or synthetic collagens. Analysis of
      natural collagen sequences indicates low similarity between the neighboring
      exons. Combining the synthetic collagen model and bioinformatic analysis provides
      insight on how fibrillar collagens might have arisen from the duplication of
      smaller domains. 

PMID- 24043621
TI  - An additional function of the rough endoplasmic reticulum protein complex prolyl
      3-hydroxylase 1.cartilage-associated protein.cyclophilin B: the CXXXC motif
      reveals disulfide isomerase activity in vitro.
AB  - Collagen biosynthesis occurs in the rough endoplasmic reticulum, and many
      molecular chaperones and folding enzymes are involved in this process. The
      folding mechanism of type I procollagen has been well characterized, and protein
      disulfide isomerase (PDI) has been suggested as a key player in the formation of
      the correct disulfide bonds in the noncollagenous carboxyl-terminal and amino
      terminal propeptides. Prolyl 3-hydroxylase 1 (P3H1) forms a hetero-trimeric
      complex with cartilage-associated protein and cyclophilin B (CypB). This complex
      is a multifunctional complex acting as a prolyl 3-hydroxylase, a peptidyl prolyl
      cis-trans isomerase, and a molecular chaperone. Two major domains are predicted
      from the primary sequence of P3H1: an amino-terminal domain and a carboxyl
      terminal domain corresponding to the 2-oxoglutarate- and iron-dependent
      dioxygenase domains similar to the alpha-subunit of prolyl 4-hydroxylase and
      lysyl hydroxylases. The amino-terminal domain contains four CXXXC sequence
      repeats. The primary sequence of cartilage-associated protein is homologous to
      the amino-terminal domain of P3H1 and also contains four CXXXC sequence repeats.
      However, the function of the CXXXC sequence repeats is not known. Several
      publications have reported that short peptides containing a CXC or a CXXC
      sequence show oxido-reductase activity similar to PDI in vitro. We hypothesize
      that CXXXC motifs have oxido-reductase activity similar to the CXXC motif in PDI.
      We have tested the enzyme activities on model substrates in vitro using a GCRALCG
      peptide and the P3H1 complex. Our results suggest that this complex could
      function as a disulfide isomerase in the rough endoplasmic reticulum. 

PMID- 24043623
TI  - Jun activation domain-binding protein 1 (JAB1) is required for the optimal
      response to interferons.
AB  - Degradation of IFN receptor (IFNR) protein is one of the mechanisms to limit the
      extent of cellular responses to interferons. Tyrosine kinase 2 (TYK2), a JAK
      family kinase, has been reported to bind to and stabilize IFNR, indicating that
      TYK2 is a fundamental component of IFNR complex. Herein, we identified Jun
      activation domain-binding protein 1 (JAB1) as a new TYK2 binding partner and
      investigated its role in the regulation of IFN responses. siRNA knockdown of JAB1
      resulted in suppression of IFN-induced phosphorylation of STAT proteins and their
      transcriptional activation. Importantly, JAB1 knockdown induced the activation of
      SCF ubiquitin ligase complex containing Cullin 1 (CUL1), as judged by the
      enhancement of covalent modification of CUL1 with the ubiquitin-like protein
      NEDD8, and markedly reduced the basal protein level of IFNR. In contrast, NEDD8
      knockdown or inhibition of NEDD8 modification by NEDD8-activating enzyme
      inhibitor resulted in increased IFNR protein concomitantly with a reduction of
      NEDD8-modified CUL1. Furthermore, NEDD8-activating enzyme inhibitor treatment
      enhanced the susceptibility to IFN-alpha in HeLa cells. These data suggest that
      the NEDD8 modification pathway is involved in the proteolysis of IFNR and that
      JAB1 acts as a positive regulator of IFN responses by stabilizing IFNR through
      antagonizing the NEDD8 pathway. 

PMID- 24043624
TI  - Role of glycoside phosphorylases in mannose foraging by human gut bacteria.
AB  - To metabolize both dietary fiber constituent carbohydrates and host glycans
      lining the intestinal epithelium, gut bacteria produce a wide range of
      carbohydrate-active enzymes, of which glycoside hydrolases are the main
      components. In this study, we describe the ability of phosphorylases to
      participate in the breakdown of human N-glycans, from an analysis of the
      substrate specificity of UhgbMP, a mannoside phosphorylase of the GH130 protein
      family discovered by functional metagenomics. UhgbMP is found to phosphorolyze
      beta-D-Manp-1,4-beta-D-GlcpNAc-1,4-D-GlcpNAc and is also a highly efficient
      enzyme to catalyze the synthesis of this precious N-glycan core oligosaccharide
      by reverse phosphorolysis. Analysis of sequence conservation within family GH130,
      mapped on a three-dimensional model of UhgbMP and supported by site-directed
      mutagenesis results, revealed two GH130 subfamilies and allowed the
      identification of key residues responsible for catalysis and substrate
      specificity. The analysis of the genomic context of 65 known GH130 sequences
      belonging to human gut bacteria indicates that the enzymes of the GH130_1
      subfamily would be involved in mannan catabolism, whereas the enzymes belonging
      to the GH130_2 subfamily would rather work in synergy with glycoside hydrolases
      of the GH92 and GH18 families in the breakdown of N-glycans. The use of GH130
      inhibitors as therapeutic agents or functional foods could thus be considered as
      an innovative strategy to inhibit N-glycan degradation, with the ultimate goal of
      protecting, or restoring, the epithelial barrier.

PMID- 24043625
TI  - Serum- and glucocorticoid-induced protein kinase 1 (SGK1) is regulated by store
      operated Ca2+ entry and mediates cytoprotection against necrotic cell death.
AB  - Serum and glucocorticoid-regulated kinase 1 (SGK1) encodes a phosphatidylinositol
      3-kinase-dependent serine/threonine kinase that is rapidly induced in response to
      cellular stressors and is an important cell survival signal. Previous studies
      have suggested that an increase in cytoplasmic Ca(2+) concentration ([Ca(2+)]c)
      is required for increased SGK1 expression, but the subcellular source of Ca(2+)
      regulating SGK1 transcription remains uncertain. Activation of endoplasmic
      reticulum stress (ERS) with thapsigargin (TG) increased SGK1 mRNA and protein
      expression in MDA-MB-231 cells. Intracellular Ca(2+) imaging revealed that store
      operated Ca(2+) entry played a prominent role in SGK1 induction by TG. Neither
      ERS nor release of Ca(2+) from the ER was sufficient to activate SGK1. Prolonged
      elevation of intracellular Ca(2+) levels, however, triggered cell death with a
      much greater proportion of the cells undergoing necrosis rather than apoptosis. A
      relative increase in the percentage of cells undergoing necrosis was observed in
      cells expressing a short hairpin RNA targeted to the SGK1 gene. Necrotic cell
      death evoked by cytoplasmic Ca(2+) overloading was associated with persistent
      hyperpolarization of the inner mitochondrial membrane and a modest increase in
      calpain activation, but did not involve detectable caspase 3 or caspase 7
      activation. The effects of cytoplasmic Ca(2+) overloading on mitochondrial
      membrane potential were significantly reduced in cells expressing SGK1 compared
      with SGK1-depleted cells. Our findings indicate that store-operated Ca(2+) entry
      regulates SGK1 expression in epithelial cells and suggest that SGK1-dependent
      cytoprotective signaling involves effects on maintaining mitochondrial function. 

PMID- 24043626
TI  - Determinants of 14-3-3sigma protein dimerization and function in drug and
      radiation resistance.
AB  - Many proteins exist and function as homodimers. Understanding the detailed
      mechanism driving the homodimerization is important and will impact future
      studies targeting the "undruggable" oncogenic protein dimers. In this study, we
      used 14-3-3sigma as a model homodimeric protein and performed a systematic
      investigation of the potential roles of amino acid residues in the interface for
      homodimerization. Unlike other members of the conserved 14-3-3 protein family, 14
      3-3sigma prefers to form a homodimer with two subareas in the dimeric interface
      that has 180 degrees  symmetry. We found that both subareas of the dimeric
      interface are required to maintain full dimerization activity. Although the
      interfacial hydrophobic core residues Leu(12) and Tyr(84) play important roles in
      14-3-3sigma dimerization, the non-core residue Phe(25) appears to be more
      important in controlling 14-3-3sigma dimerization activity. Interestingly, a
      similar non-core residue (Val(81)) is less important than Phe(25) in contributing
      to 14-3-3sigma dimerization. Furthermore, dissociating dimeric 14-3-3sigma into
      monomers by mutating the Leu(12), Phe(25), or Tyr(84) dimerization residue
      individually diminished the function of 14-3-3sigma in resisting drug-induced
      apoptosis and in arresting cells at G2/M phase in response to DNA-damaging
      treatment. Thus, dimerization appears to be required for the function of 14-3
      3sigma. 

PMID- 24043627
TI  - Biochemical analysis of the Plasmodium falciparum erythrocyte-binding antigen-175
      (EBA175)-glycophorin-A interaction: implications for vaccine design.
AB  - PfEBA175 has an important role in the invasion of human erythrocytes by
      Plasmodium falciparum and is therefore considered a high priority blood-stage
      malaria vaccine candidate. PfEBA175 mediates adhesion to erythrocytes through
      binding of the Duffy-binding-like (DBL) domains in its extracellular domain to
      Neu5Acalpha2-3Gal displayed on the O-linked glycans of glycophorin-A (GYPA).
      Because of the difficulties in expressing active full-length (FL) P. falciparum
      proteins in a recombinant form, previous analyses of the PfEBA175-GYPA
      interaction have largely focused on the DBL domains alone, and therefore they
      have not been performed in the context of the native protein sequence. Here, we
      express the entire ectodomain of PfEBA175 (PfEBA175 FL) in soluble form, allowing
      us to compare the biochemical and immunological properties with a fragment
      containing only the tandem DBL domains ("region II," PfEBA175 RII). Recombinant
      PfEBA175 FL bound human erythrocytes in a trypsin and neuraminidase-sensitive
      manner and recognized Neu5Acalpha2-3Gal-containing glycans, confirming its
      biochemical activity. A quantitative binding analysis showed that PfEBA175 FL
      interacted with native GYPA with a KD ~0.26 MUM and is capable of self
      association. By comparison, the RII fragment alone bound GYPA with a lower
      affinity demonstrating that regions outside of the DBL domains are important for
      interactions with GYPA; antibodies directed to these other regions also
      contributed to the inhibition of parasite invasion. These data demonstrate the
      importance of PfEBA175 regions other than the DBL domains in the interaction with
      GYPA and merit their inclusion in an EBA175-based vaccine.

PMID- 24043628
TI  - Balanced production of ribosome components is required for proper G1/S transition
      in Saccharomyces cerevisiae.
AB  - Cell cycle regulation is a very accurate process that ensures cell viability and
      the genomic integrity of daughter cells. A fundamental part of this regulation
      consists in the arrest of the cycle at particular points to ensure the completion
      of a previous event, to repair cellular damage, or to avoid progression in
      potentially risky situations. In this work, we demonstrate that a reduction in
      nucleotide levels or the depletion of RNA polymerase I or III subunits generates
      a cell cycle delay at the G1/S transition in Saccharomyces cerevisiae. This delay
      is concomitant with an imbalance between ribosomal RNAs and proteins which, among
      others, provokes an accumulation of free ribosomal protein L5. Consistently with
      a direct impact of free L5 on the G1/S transition, rrs1 mutants, which weaken the
      assembly of L5 and L11 on pre-60S ribosomal particles, enhance both the G1/S
      delay and the accumulation of free ribosomal protein L5. We propose the existence
      of a surveillance mechanism that couples the balanced production of yeast
      ribosomal components and cell cycle progression through the accumulation of free
      ribosomal proteins. This regulatory pathway resembles the p53-dependent nucleolar
      stress checkpoint response described in human cells, which indicates that this is
      a general control strategy extended throughout eukaryotes. 

PMID- 24043629
TI  - A Lactobacillus rhamnosus GG-derived soluble protein, p40, stimulates ligand
      release from intestinal epithelial cells to transactivate epidermal growth factor
      receptor.
AB  - p40, a Lactobacillus rhamnosus GG (LGG)-derived soluble protein, ameliorates
      intestinal injury and colitis, reduces apoptosis, and preserves barrier function
      by transactivation of the EGF receptor (EGFR) in intestinal epithelial cells. The
      aim of this study is to determine the mechanisms by which p40 transactivates the
      EGFR in intestinal epithelial cells. Here we show that p40-conditioned medium
      activates EGFR in young adult mouse colon epithelial cells and human colonic
      epithelial cell line, T84 cells. p40 up-regulates a disintegrin and
      metalloproteinase domain-containing protein 17 (ADAM17) catalytic activity, and
      broad spectrum metalloproteinase inhibitors block EGFR transactivation by p40 in
      these two cell lines. In ADAM17-deficient mouse colonic epithelial (ADAM17(-/-)
      MCE) cells, p40 transactivation of EGFR is blocked, but can be rescued by re
      expression with WT ADAM17. Furthermore, p40 stimulates release of heparin binding
      (HB)-EGF, but not transforming growth factor (TGF)alpha or amphiregulin, in young
      adult mouse colon cells and ADAM17(-/-) MCE cells overexpressing WT ADAM17.
      Knockdown of HB-EGF expression by siRNA suppresses p40 effects on transactivating
      EGFR and Akt, preventing apoptosis, and preserving tight junction function. The
      effects of p40 on HB-EGF release and ADAM17 activation in vivo are examined after
      administration of p40-containing pectin/zein hydrogel beads to mice. p40
      stimulates ADAM17 activity and EGFR activation in colonic epithelial cells and
      increases HB-EGF levels in blood from WT mice, but not from mice with intestinal
      epithelial cell-specific ADAM17 deletion. Thus, these data define a mechanism of
      a probiotic-derived soluble protein in modulating intestinal epithelial cell
      homeostasis through ADAM17-mediated HB-EGF release, leading to transactivation of
      EGFR. 

PMID- 24043630
TI  - The unfolded protein response transducer ATF6 represents a novel transmembrane
      type endoplasmic reticulum-associated degradation substrate requiring both
      mannose trimming and SEL1L protein.
AB  - Proteins misfolded in the endoplasmic reticulum (ER) are cleared by the ubiquitin
      dependent proteasome system in the cytosol, a series of events collectively
      termed ER-associated degradation (ERAD). It was previously shown that SEL1L, a
      partner protein of the E3 ubiquitin ligase HRD1, is required for degradation of
      misfolded luminal proteins (ERAD-Ls substrates) but not misfolded transmembrane
      proteins (ERAD-Lm substrates) in both mammalian and chicken DT40 cells. Here, we
      analyzed ATF6, a type II transmembrane glycoprotein that serves as a
      sensor/transducer of the unfolded protein response, as a potential ERAD-Lm
      substrate in DT40 cells. Unexpectedly, degradation of endogenous ATF6 and
      exogenously expressed chicken and human ATF6 by the proteasome required SEL1L.
      Deletion analysis revealed that the luminal region of ATF6 is a determinant for
      SEL1L-dependent degradation. Chimeric analysis showed that the luminal region of
      ATF6 confers SEL1L dependence on type I transmembrane protein as well. In
      contrast, degradation of other known type I ERAD-Lm substrates (BACE457, T-cell
      receptor-alpha, CD3-delta, and CD147) did not require SEL1L. Thus, ATF6
      represents a novel type of ERAD-Lm substrate requiring SEL1L for degradation
      despite its transmembrane nature. In addition, endogenous ATF6 was markedly
      stabilized in wild-type cells treated with kifunensine, an inhibitor of alpha1,2
      mannosidase in the ER, indicating that degradation of ATF6 requires proper
      mannose trimming. Our further analyses revealed that the five ERAD-Lm substrates
      examined are classified into three subgroups based on their dependence on mannose
      trimming and SEL1L. Thus, ERAD-Lm substrates are degraded through much more
      diversified mechanisms in higher eukaryotes than previously thought. 

PMID- 24043631
TI  - MUC1-C oncoprotein activates ERK->C/EBPbeta signaling and induction of aldehyde
      dehydrogenase 1A1 in breast cancer cells.
AB  - Aldehyde dehydrogenase 1A1 (ALDH1A1) activity is used as a marker of breast
      cancer stem cells; however, little is known about the regulation of ALDH1A1
      expression. Mucin 1 (MUC1) is a heterodimeric protein that is aberrantly
      overexpressed in most human breast cancers. In studies of breast cancer cells
      stably silenced for MUC1 or overexpressing the oncogenic MUC1-C subunit, we
      demonstrate that MUC1-C is sufficient for induction of MEK -> ERK signaling and
      that treatment with a MUC1-C inhibitor suppresses ERK activation. In turn, MUC1-C
      induces ERK-mediated phosphorylation and activation of the CCAAT/enhancer-binding
      protein beta (C/EBPbeta) transcription factor. The results further show that MUC1
      C and C/EBPbeta form a complex on the ALDH1A1 gene promoter and activate ALDH1A1
      gene transcription. MUC1-C-induced up-regulation of ALDH1A1 expression is
      associated with increases in ALDH activity and is detectable in stem-like cells
      when expanded as mammospheres. These findings demonstrate that MUC1-C (i)
      activates a previously unrecognized ERK->C/EBPbeta->ALDH1A1 pathway, and (ii)
      promotes the induction of ALDH activity in breast cancer cells.

PMID- 24043632
TI  - Implications of a vasodilatory human monoclonal autoantibody in postural
      hypotension.
AB  - Functional autoantibodies to the autonomic receptors are increasingly recognized
      in the pathophysiology of cardiovascular diseases. To date, no human activating
      monoclonal autoantibodies to these receptors have been available. In this study,
      we describe for the first time a beta2-adrenergic receptor (beta2AR)-activating
      monoclonal autoantibody (C5F2) produced from the lymphocytes of a patient with
      idiopathic postural hypotension. C5F2, an IgG3 isotype, recognizes an epitope in
      the N terminus of the second extracellular loop (ECL2) of beta2AR. Surface
      plasmon resonance analysis revealed high binding affinity for the beta2AR ECL2
      peptide. Immunoblotting and immunofluorescence demonstrated specific binding to
      beta2AR in H9c2 cardiomyocytes, CHO cells expressing human beta2AR, and rat
      aorta. C5F2 stimulated cyclic AMP production in beta2AR-transfected CHO cells and
      induced potent dilation of isolated rat cremaster arterioles, both of which were
      specifically blocked by the beta2AR-selective antagonist ICI-118551 and by the
      beta2AR ECL2 peptide. This monoclonal antibody demonstrated sufficient activity
      to produce postural hypotension in its host. Its availability provides a unique
      opportunity to identify previously unrecognized causes and new pharmacological
      management of postural hypotension and other cardiovascular diseases. 

PMID- 24043634
TI  - WNT10A variants are associated with non-syndromic tooth agenesis in the general
      population.
AB  - Tooth agenesis is the most common developmental dental anomaly. Absence of one or
      two permanent teeth is found in the majority of affected subjects. Very few
      patients suffer severe tooth agenesis. Recent studies revealed that WNT10A gene
      mutations caused syndromic and isolated severe tooth agenesis. In this study, to
      determine the contribution of WNT10A variants in different severities of tooth
      agenesis, we investigated the association between WNT10A variants and non
      syndromic tooth agenesis in a Chinese population consisting of 505 tooth agenesis
      patients and 451 normal controls. Twenty-three novel non-synonymous variants were
      identified. WNT10A variants were detected in 15.8 % (75/474) of patients with 1-3
      missing teeth and 51.6 % (16/31) of patients with 4 or more missing teeth. As
      compared with a frequency of 3.1 % in individuals with full dentition, variant
      allele frequencies were significantly elevated in both groups with tooth agenesis
      (p values of 1.00 * 10(-6) and 3.89 * 10(-23), respectively). Our findings showed
      that WNT10A variants were associated with non-syndromic tooth agenesis from mild
      to severe tooth agenesis, and the more severe tooth agenesis, the stronger
      association. Biallelic genotypes of WNT10A variants may have a pathogenic effect
      on tooth development. Presence of a single variant allele would be predisposing
      for causation with low penetrance. Together with WNT10A variant, there should be
      other genetic or environmental factors leading to biallelic variant-related
      variable clinical manifestations and single allele variant-related low
      penetrance. The frequent missing tooth positions in the WNT10A-related cases were
      consistent with that in the general population, suggesting WNT10A plays a
      critically important role in the etiology of general tooth agenesis.

PMID- 24043637
TI  - Coagulation disorders and the IPF puzzle.

PMID- 24043638
TI  - Asthma admissions, smoking bans and administrative databases: author's response.

PMID- 24043639
TI  - The Plexin-B family and its role in cancer progression.
AB  - Plexins are transmembrane protein receptors for semaphorin molecules. These
      molecules are involved in numerous cellular activities related to cell
      proliferation, adhesion along with the basement membrane, cellular motility and
      invasive capability. All nine members of Plexins identified in vertebrates have
      been grouped into subclasses, termed Plexin-A, Plexin-B, Plexin-C and Plexin-D.
      Plexin-B consists of three members, namely Plexin-B1, Plexin-B2 and Plexin-B3.
      Plexin-B1 functionally interacts with Sema4A (Yukawa et al., 2010) and can also
      form heterodimer with Plexin-B2 for Sema4A binding (Nkyimbeng-Takwi et al.,
      2011). Plexin-B2 binds with Sema4C. Plexin-B3 mediates interaction with both
      Sema4G and Sema5A. Some semaphorines exist in a membrane-bound form only, whereas
      other family members can be found in tissues/fluids in both secreted and membrane
      bound forms. This ligand-receptor interaction between sema4D and Plexin-B1
      indicated in different signaling pathways results in many intriguing and
      interesting findings, highlighting its importance in both physiology and
      pathology. Apart from bidirectional signaling among these molecules, the
      involvement of Plexin-B1 in the processes described here directly involves a
      bidirectional singaling between Sema4Dand Plexin-B1. Being a high affinity
      receptor for both Sema4A and Sema4D, the role played by Plexin-B1 in cancer
      progression, metastasis and angiogenesis is still an area requiring further
      research. Activation of Sema4D mediated downstream effectors is largely
      influenced by cross talk of Plexin-B1 with other molecules, such as Her-2 and
      Met. In this review, all findings regarding Plexin-B1 upstream and downstream
      regulation and its putative involvement in relation to the ultimate fate of
      cancer cells are discussed.

PMID- 24043640
TI  - Trends in biological joint resurfacing.
AB  - The treatment of osteochondral lesions and osteoarthritis remains an ongoing
      clinical challenge in orthopaedics. This review examines the current research in
      the fields of cartilage regeneration, osteochondral defect treatment, and
      biological joint resurfacing, and reports on the results of clinical and pre
      clinical studies. We also report on novel treatment strategies and discuss their
      potential promise or pitfalls. Current focus involves the use of a scaffold
      providing mechanical support with the addition of chondrocytes or mesenchymal
      stem cells (MSCs), or the use of cell homing to differentiate the organism's own
      endogenous cell sources into cartilage. This method is usually performed with
      scaffolds that have been coated with a chemotactic agent or with structures that
      support the sustained release of growth factors or other chondroinductive agents.
      We also discuss unique methods and designs for cell homing and scaffold
      production, and improvements in biological joint resurfacing. There have been a
      number of exciting new studies and techniques developed that aim to repair or
      restore osteochondral lesions and to treat larger defects or the entire articular
      surface. The concept of a biological total joint replacement appears to have much
      potential. Cite this article: Bone Joint Res 2013;2:193-9. 

PMID- 24043641
TI  - Comparison of esophagogastric junction distensibility changes during POEM and
      Heller myotomy using intraoperative FLIP.
AB  - BACKGROUND: Peroral endoscopic myotomy (POEM) is a novel endoscopic surgical
      procedure for the treatment of achalasia. The comparative effects of POEM and
      laparoscopic Heller myotomy (LHM) on esophagogastric junction (EGJ) physiology
      are unknown. A novel measurement catheter, the functional lumen imaging probe
      (FLIP), allows for intraoperative evaluation of EGJ compliance by measuring
      luminal geometry and pressure during volume-controlled distensions. METHODS:
      Distensibility index (DI) (defined as the minimum cross-sectional area at the EGJ
      divided by pressure) was measured with FLIP intraoperatively in patients
      undergoing LHM and POEM. Separate measurements were taken after each operative
      step. During LHM, measurements were performed after: (1) induction of anesthesia,
      (2) insufflation of pneumoperitoneum, (3) hiatal dissection and esophageal
      mobilization, (4) myotomy, (5) partial fundoplication, and (6) deinsufflation.
      During POEM, they were performed after: (1) induction of anesthesia, (2)
      submucosal tunnel creation, and (3) myotomy. RESULTS: Eleven LHM and 14 POEM
      patients underwent intraoperative FLIP. Baseline DI was similar between groups.
      LHM resulted in an overall increase in mean DI (pre 1.4 vs. post 7.6 mm(2)/mmHg,
      using a 40-ml distension volume; p < 0.001). Insufflation of pneumoperitoneum and
      hiatal dissection did not affect DI. Myotomy caused an increase in DI. Partial
      fundoplication (6 Toupet, 5 Dor) caused a decrease in DI, and deinsufflation
      caused an increase in DI. POEM also resulted in an overall increase in mean DI
      (pre 1.4 vs. post 7.9 mm(2)/mmHg; p < 0.001). Measured individually, both
      submucosal tunnel creation and myotomy caused increases in DI. When overall
      changes were compared, there were no differences in the amount of DI increase
      between LHM and POEM. CONCLUSIONS: POEM and LHM result in a similar improvement
      in EGJ distensibility intraoperatively. Further study is needed to correlate
      intraoperative FLIP measurements with postoperative symptomatic and physiologic
      outcomes.

PMID- 24043642
TI  - Guidelines for laparoscopic treatment of ventral and incisional abdominal wall
      hernias (International Endohernia Society [IEHS])-Part III.

PMID- 24043643
TI  - Feasibility of the trans-umbilical route compared with the trans-oral route in
      gastric upper body endoscopic submucosal dissection: a porcine model.
AB  - BACKGROUND: Total gastrectomy is performed for early gastric cancer in the upper
      body of the stomach because of the high complication rate of endoscopic
      submucosal dissection (ESD). The aims of the present animal study in pigs were to
      verify: (1) the feasibility of the trans-umbilical route compared with the trans
      oral route in gastric upper body ESD; (2) the non-inferiority of single port
      laparoscopic lymph node dissection (LLND) compared with multiport LLND; and (3)
      the safety of 2-basin LLND (upper greater and lesser curvature). METHODS: We
      separated the pigs (~40 kg each) into two groups: conventional and experimental
      (n = 5 per group). We performed ESD in the fundus and upper body anterior wall
      (UBAW) via the trans-oral route and multiport LLND in the conventional group, and
      via the trans-umbilical route and single port LLND in the experimental group.
      RESULTS: The completion rates, tissue weights, and specimen diameters of both
      routes showed no statistical differences in either the fundus or the UBAW. The
      operative time was shorter with the trans-umbilical route than with the trans
      oral route in both areas (p < 0.05). In LLND, there were no differences in
      surgical outcomes between the multiport and single port groups. Intraoperative
      perforation was seen in the trans-oral route group (n = 1). Delayed perforation
      was observed in 30 % of the ESD sites. CONCLUSIONS: The trans-umbilical route is
      feasible and has lower complication rates than the trans-oral route in gastric
      upper body ESD. Additionally, single port LLND is not inferior to multiport LLND,
      and one-side-basin dissection is safer than two-side.

PMID- 24043644
TI  - Reply to: "Comparison of results from a randomized trial 1 year after
      laparoscopic Nissen and Toupet fundoplications".

PMID- 24043645
TI  - Clinical markers of the hypercoagulable state by rotational thrombelastometry in
      obese patients submitted to bariatric surgery.
AB  - BACKGROUND: Metabolic and inflammatory disturbances associated with obesity are
      considered important trigger factors for venous thromboembolism (VTE).
      Identification of clinical markers indicating a hypercoagulability state could
      define a group of high-risk patients in the surgical setting. This study aimed to
      identify these markers using rotational thrombelastometry (ROTEM) analysis, an
      established method for hemostasis testing that can detect hyperfunctional stages
      of the clotting process. METHODS: From June to December 2010, this study
      investigated 109 consecutive obese patients (28 women and 22 men, mean age 46
      years, body mass index 46.6 +/- 7 kg/m(2)) with no history of VTE who were
      candidates for bariatric surgery. Preoperative clinical and metabolic
      characteristics and ROTEM analysis were recorded. Hypercoagulable risk was
      defined when patients showed a clot strength (G) of >=11 dynes/cm(2). RESULTS: Of
      the 109 patients, 20 (18%) were hypercoagulable according to ROTEM analysis.
      Metabolic/inflammatory biomarkers such as leptin, C-reactive protein, fibrinogen
      levels, and platelet count were significantly higher in the high-risk patients.
      In the multivariate analysis, fibrinogen was an independent predictor of G >= 11
      dynes/cm(2) [odds ratio (OR) 2.92, 95 % confidence interval (CI) 1.80-5.21, p =
      0.023]. After adjustment to other data, only waist circumference affected the
      prediction [OR 4.42, 95 % CI 2.27-6.71, p = 0.009]. Receiver operating
      characteristic curve analysis showed that 3.95 g/l was the best cutoff point for
      fibrinogen predictability (sensitivity 100 %, specificity 41%). CONCLUSION: A
      hypercoagulability state in obese patients is associated with central obesity and
      high fibrinogen levels, which should be considered clinical hallmarks of this
      state. More aggressive perioperative prophylaxis for VTE should be recommended
      when these hallmarks are present in obese patients.

PMID- 24043646
TI  - Second-generation colon capsule endoscopy is feasible in the out-of-clinic
      setting.
AB  - BACKGROUND: No colorectal imaging test may be performed on an out-of-clinic
      basis. This represents a major drawback compared with fecal tests. Because colon
      capsule endoscopy (CCE) automatically detects small bowel mucosa, it has the
      potential to become the first colorectal imaging test to be performed out-of
      clinic. This study aimed to evaluate the feasibility and efficiency of CCE when
      offered as an out-of-clinic procedure. METHODS: Patients with known or suspected
      colonic diseases who had up to 40 min of travel time from clinic to home were
      offered CCE as an out-of-clinic procedure. These patients were provided with four
      numbered vials (1 with metoclopramide, 2 with sodium phosphate, 1 with bisacodyl)
      and detailed instructions on how to interact with data-recorder automatic
      signaling. Patient compliance with data-recorder instructions, CCE excretion, and
      detection rates were prospectively assessed. RESULTS: The study enrolled 41
      patients (29 men) with a mean age of 57 years. According to data recorder DR3
      registered alerts, 14 patients (34 %) required a single booster only, 27 patients
      (66 %) required two boosters, and 13 patients (32 %) required a suppository.
      Comparison of the DR3 alerts with the returned vials showed that patient
      compliance to DR3 alerts was 100 %. During the procedure, 16 patients (39 %)
      called the physician/clinic from home. In 85 % of the cases, the CCE was excreted
      within the battery operating time. Lesions size 6 mm or larger were detected in
      10 (24 %) of the 41 patients. CONCLUSIONS: As an out-of-clinic procedure, CCE is
      feasible and easily performed. A home-based procedure may be associated with
      better acceptability and potentially with increased adherence to Colorectal
      cancer screening.

PMID- 24043647
TI  - A modified laparoscopic hernioplasty (TAPP) is the standard procedure for
      inguinal and femoral hernias: a retrospective 17-year analysis with 1,123 hernia
      repairs.
AB  - BACKGROUND: Laparoscopic and endoscopic procedures generally are accepted for
      repair of primary and recurrent hernias that follow conventional (anterior)
      repair. This report discusses transabdominal preperitoneal (TAPP) for
      incarcerated hernias, scrotal hernias, and hernias after radical prostatectomy,
      as well as hernia recurrences after TAPP and totally extraperitoneal (TEP)
      procedures (complex hernias). Studies with long-term results of hernia
      recurrences are missing. This study aimed to determine hernia recurrence rates
      for adults after a modified TAPP procedure. The records of patients who had
      hernia repair surgery at a general hospital 2, 7, 12, and 17 years earlier were
      analyzed. Living patients were requested to complete a questionnaire to
      complement information from their hospital records. METHODS: A retrospective
      analysis was undertaken that included 5,764 patients who had undergone hernia
      repair surgery 2-17 years earlier at a single large center. Between 1993 and
      2009, a modified TAPP procedure was performed for 5,764 patients (median age,
      59.1 years) to repair 6,776 hernias (93.9% of all hernia repairs), including
      6,126 primary hernias (87.4%) and 884 recurrent hernias (12.6%). These included
      994 complicated hernias (14.2%) closed by a modified TAPP (89.3% of all femoral
      hernias, 85.9% of scrotal hernias, 79.1% of incarcerated hernias, and 92.7% of
      hernias after radical prostatectomy). Limited financial and staff resources did
      not permit a quantitative follow-up study within a reasonable time of all 5,764
      patients who had hernia surgery 2-18 years earlier. To obtain quantitative
      results of hernia recurrences after a modified TAPP, the patients were divided
      into four subgroups and requested to complete a questionnaire. These four patient
      subgroups whose surgeries had been performed 2 years earlier (241 patients with
      277 hernias), 7 years earlier (285 patients with 376 hernias), 12 years earlier
      (401 patients with 544 hernias), and 17 years earlier (181 patients with 222
      hernias) represented the complete group of hernia sufferers. Patients with
      symptoms after hernia surgery (n = 5) were invited for a medical checkup by a
      specialist in hernia surgery at our outpatient unit. RESULTS: The sex, age, and
      the number of complex hernias of the patients did not differ significantly among
      the four patient subgroups or in comparison with the entire group. The patients
      who had received surgery in 1994, 1999, 2004, and 2009 were quizzed by a
      questionnaire and represented all patients who had hernia surgery from 1993 to
      2009. The follow-up response of the living patients in each of the subgroups
      ranged from 89.5% of those who had hernia surgery 17 years earlier to 95.9% of
      those who had surgery 2 years earlier. The primary end point of the study was the
      hernia recurrence rate after a modified TAPP for primary, recurrent, and complex
      hernias performed 2, 7, 12, and 17 years earlier. The secondary end points of the
      study focused on the following questions: Is a modified TAPP practicable with
      acceptable recurrence rates for complex hernias? Do relapse rates show individual
      surgeon-dependent differences in relation to the learning curve? How many years
      of postoperative follow-up evaluation are required to determine quantitative
      recurrence rates (>90% recurrence)? All inguinal and femoral hernias were
      repaired with a modified TAPP procedure. Hernia defects larger than 1 * 1 cm were
      closed with nonabsorbable sutures before the mesh was implanted. Within 17 years
      after surgery, 4 (4.3%) of the 94 study participants treated with a modified TAPP
      procedure for primary or recurrent inguinal and femoral hernias experienced
      recurrent hernias (4 recurrences after 117 hernioplasties, 3.4%). Within 12 years
      after surgery, 4 (1 %) of 302 patients experienced recurrent hernias (4
      recurrences after 398 modified TAPP procedures, 1%). Within 7 years after surgery
      for inguinal or femoral hernias, 8 (3.2%) of 251 patients had relapsed (8
      recurrences after 337 modified TAPP procedures, 2.4%). Within 2 years after a
      modified TAPP, only 1 of 230 patients (0.4%) experienced a recurrent hernia (1
      relapse after 265 hernioplasties, 0.4%). After the modified TAPP procedure, 52.9%
      (n = 9) of the patients with a recurrent hernia had a second repair at our
      hospital, and 35.3% (n = 6) had the second repair at other hospitals, whereas 2
      patients (11.8 %) renounced a repeat surgical intervention. The recurrence rate
      after a modified TAPP procedure for all the patients (n = 896) was 1.8%. The
      study participants with primary hernias (n = 765) had a 1.7% recurrence rate,
      whereas the rate for recurrent hernias after anterior repair (n = 131) was 2.3 %.
      Incarcerated hernias (n = 47) and hernias after radical prostatectomy (n = 22)
      that were closed by the modified TAPP procedure resulted in no hernia
      recurrences. Only 1 of 47 patients with scrotal hernias had a hernia relapse. Of
      all the hernia recurrences between 1993 and 2009 (n = 76), 60.5% (n = 46)
      developed within 2 years after surgery, whereas 15.8% (n = 12) occurred after
      more than 5 years, and 4% (n = 3) occurred after more than 10 years. The
      recurrence rates also were higher for surgeons in the early period after
      completion of their personal learning curves (<50 modified TAPP procedures
      performed on their own responsibility). CONCLUSIONS: In a retrospective long-term
      study (2-17 years) from a single center with 1,108 patients and 1,123 modified
      TAPP procedures (93.9% of all hernia repairs), the hernia recurrence rate was
      1.7% for adults with primary hernias (n = 765 patients) and 2.3% for adults with
      recurrent hernias after anterior repair (n = 131 patients). A modified TAPP
      procedure with suturing of hernia defects larger than 1 * 1 cm can be used as the
      standard procedure without recurrences for femoral hernias, incarcerated hernias,
      and hernias after radical prostatectomy, with low recurrence rates for scrotal
      hernias (2%). To collect quantitative data on hernia recurrence rates,
      postoperative follow-up studies longer than 10 years are needed (4% of
      recurrences developed later than 10 years after surgery).

PMID- 24043648
TI  - Automatic glare removal in endoscopic imaging.
AB  - BACKGROUND: Glare from surgical instruments and tissue surfaces often occurs
      during endoscopic procedures and can be disturbing to the operator. The
      brightness level of the light source can be reduced, but at the expense of
      overall image clarity, so alternative solutions are needed for removing glare.
      Digital image-processing methods offer the opportunity to lessen or eliminate
      glare by reducing the intensity of the affected parts of the image. This study
      investigated a new automated method for glare reduction that uses two different
      intensity thresholds as a basis for applying glare reduction processes and it
      also reduces unpleasant artifacts at the glare region boundaries. METHODS: The
      new glare-reduction method was compared with a previous method. Three variants of
      each method, each with different color biases in the glare regions, were applied
      to a 20-s surgical recording containing substantial amounts of glare. The six
      versions and the original recording were evaluated subjectively by a group of 10
      experienced surgeons using a paired-comparisons method, in which each version was
      compared for preference with all the other versions. RESULTS: The new double
      threshold intensity-subtraction method scored significantly higher than the
      previously developed glare-reduction method (p < 0.05). It also scored higher
      than the original (unprocessed) version, but not significantly. The color bias
      was important, with combinations of pink and grey performing better than yellow
      tints. CONCLUSIONS: The findings show the new method to be a significant
      improvement in automatic glare reduction compared with earlier methods. The
      method is not computationally demanding, so it can in the future be evaluated
      clinically in high-definition endoscopic imaging systems and developed further in
      this environment.

PMID- 24043649
TI  - Growth and function in childhood of a normal solitary kidney from birth or from
      early infancy.
AB  - BACKGROUND: Children with a solitary kidney (SK) have an increased long-term risk
      of hypertension, albuminuria and glomerulosclerosis. In this study, we assessed
      the early signs of impaired glomerular filtration in children with a SK from
      birth or from early infancy. METHODS: Renal growth and function at ages 4-15.5
      years were studied in 38 children with SK and 40 matched control subjects in
      terms of accelerated growth. RESULTS: The systolic/diastolic blood pressure Z
      scores (p = 0.01/<0.05) and the resistance index (RI) of the arcuate arteries (p
      = 0.05) were higher in the children with SK. Creatinine clearance and 24-h
      protein and albumin urinary excretion showed no difference. All but seven
      children with SK had 99mTc diethylene-triamine pentaacetic acid glomerular
      filtration rate values of >80 ml/min/1.73 m(2). An independent positive
      correlation was found between length of the follow-up time and 24-h albumin
      urinary excretion (beta = 0.54, p < 0.01). Accelerated postnatal growth was
      positively related with kidney volume (beta = 0.35, p < 0.05). CONCLUSIONS: Among
      our patient cohort, renal function was well preserved at ages 4-15.5 years in
      children who were born with a SK. However, both their higher blood pressure and
      RI and the correlation of 24-h albumin urinary excretion with length of follow-up
      time underline the need for monitoring to detect early signs of glomerular
      hyperfiltration and, if necessary, implement timely intervention. SK hypertrophy
      was found to be correlated with postnatal growth.

PMID- 24043650
TI  - Patchy hair loss in an otherwise healthy man.

PMID- 24043651
TI  - Chronic inflammation as a determinant of future aging phenotypes.
AB  - BACKGROUND: The importance of chronic inflammation as a determinant of aging
      phenotypes may have been underestimated in previous studies that used a single
      measurement of inflammatory markers. We assessed inflammatory markers twice over
      a 5-year exposure period to examine the association between chronic inflammation
      and future aging phenotypes in a large population of men and women. METHODS: We
      obtained data for 3044 middle-aged adults (28.2% women) who were participating in
      the Whitehall II study and had no history of stroke, myocardial infarction or
      cancer at our study's baseline (1997-1999). Interleukin-6 was measured at
      baseline and 5 years earlier. Cause-specific mortality, chronic disease and
      functioning were ascertained from hospital data, register linkage and clinical
      examinations. We used these data to create 4 aging phenotypes at the 10-year
      follow-up (2007-2009): successful aging (free of major chronic disease and with
      optimal physical, mental and cognitive functioning), incident fatal or nonfatal
      cardiovascular disease, death from noncardiovascular causes and normal aging (all
      other participants). RESULTS: Of the 3044 participants, 721 (23.7%) met the
      criteria for successful aging at the 10-year follow-up, 321 (10.6%) had
      cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and
      the remaining 1855 (60.9%) were included in the normal aging phenotype. After
      adjustment for potential confounders, having a high interleukin-6 level (> 2.0
      ng/L) twice over the 5-year exposure period nearly halved the odds of successful
      aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval
      [CI] 0.38-0.74) and increased the risk of future cardiovascular events (OR 1.64,
      95% CI 1.15-2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58-3.80).
      INTERPRETATION: Chronic inflammation, as ascertained by repeat measurements, was
      associated with a range of unhealthy aging phenotypes and a decreased likelihood
      of successful aging. Our results suggest that assessing long-term chronic
      inflammation by repeat measurement of interleukin-6 has the potential to guide
      clinical practice.

PMID- 24043652
TI  - Risk of tick-borne infections on the rise.

PMID- 24043654
TI  - Addressing cost-related barriers to prescription drug use in Canada.

PMID- 24043655
TI  - Ubiquitous preservative blamed for rash of skin allergies.

PMID- 24043656
TI  - Inuit leaders announce national Inuit suicide-prevention strategy.

PMID- 24043657
TI  - Salon. I just played one on TV ...

PMID- 24043658
TI  - Suicide prevention training saves lives in Nunavut.

PMID- 24043659
TI  - Supervised injection sites: prejudice should not trump evidence of benefit.

PMID- 24043660
TI  - US conflict-of-interest case draws attention across continent.

PMID- 24043662
TI  - Risk of suicide 40 times higher for Inuit boys.

PMID- 24043661
TI  - Efficacy and safety of cognitive enhancers for patients with mild cognitive
      impairment: a systematic review and meta-analysis.
AB  - BACKGROUND: Cognitive enhancers, including cholinesterase inhibitors and
      memantine, are used to treat dementia, but their effectiveness for mild cognitive
      impairment is unclear. We conducted a systematic review to examine the efficacy
      and safety of cognitive enhancers for mild cognitive impairment. METHODS: Our
      eligibility criteria were studies of the effects of donepezil, rivastigmine,
      galantamine or memantine on mild cognitive impairment reporting cognition,
      function, behaviour, global status, and mortality or harms. We identified
      relevant material by searching electronic databases (e.g., MEDLINE, Embase), the
      references of included studies, trial registries and conference proceedings, and
      by contacting experts. Two reviewers independently screened the results of the
      literature search, abstracted data and appraised risk of bias using the Cochrane
      risk-of-bias tool. RESULTS: We screened 15,554 titles and abstracts and 1384 full
      text articles. Eight randomized clinical trials and 3 companion reports met our
      inclusion criteria. We found no significant effects of cognitive enhancers on
      cognition (Mini-Mental State Examination: 3 randomized clinical trials [RCTs],
      mean difference [MD] 0.14, 95% confidence interval [CI] -0.22 to 0.50;
      Alzheimer's Disease Assessment Scale - cognition subscale: 3 RCTs, standardized
      MD -0.07, 95% CI-0.16 to 0.01]) or function (Alzheimer's Disease Cooperative
      Study activities of daily living inventory: 2 RCTs, MD 0.30, 95% CI -0.26 to
      0.86). Cognitive enhancers were associated with higher risks of nausea, diarrhea
      and vomiting than placebo. INTERPRETATION: Cognitive enhancers did not improve
      cognition or function among patients with mild cognitive impairment and were
      associated with a greater risk of gastrointestinal harms. Our findings do not
      support the use of cognitive enhancers for mild cognitive impairment.

PMID- 24043663
TI  - Habit-tic deformity.

PMID- 24043665
TI  - Influence of midsole hardness of standard cushioned shoes on running-related
      injury risk.
AB  - BACKGROUND: In this double-blind randomised controlled trial, we tested if
      leisure-time runners using shoes with less compliant midsoles have a higher
      running-related injury (RRI) risk. METHOD: We provided 247 runners with standard
      running shoes having either a soft study shoes (soft-SS) or a hard study shoes
      (hard-SS) midsole and followed them prospectively for 5 months regarding RRI. All
      information about sports practice and injuries was uploaded on a dedicated
      internet platform and checked for consistency and completeness. RRI was defined
      as any first-time pain sustained during or as a result of running practice and
      impeding normal running activity for at least 1 day. Cox proportional hazards
      regressions were used to identify RRI risk factors. RESULT: The type of study
      shoes used for running was not associated with RRIs (HR=0.92; 95% CI 0.57 to
      1.48). The hard-SS had a 15% greater overall stiffness in the heel region. The
      two study groups were similar regarding personal and sports participation
      characteristics, except for years of running experience, which was higher
      (p<0.05) in the hard-SS group. Global RRI incidence was 12.1 RRI/1000 h of
      running. No between-group differences were found regarding injury location, type,
      severity or category. Nevertheless, the adjusted regression model revealed
      positive associations with RRI risk for body mass index (HR=1.126; 95% CI 1.033
      to 1.227), previous injury (HR=1.735; 95% CI 1.037 to 2.902) and mean session
      intensity (HR=1.396; 95% CI 1.040 to 1.874). Protective factors were previous
      regular running activity (HR=0.422; 95% CI 0.228 to 0.779) and weekly volume of
      other sports activities (HR=0.702; 95% CI 0.561 to 0.879). CONCLUSIONS: Midsole
      hardness of modern cushioned running shoes does not seem to influence RRI risk.

PMID- 24043666
TI  - Knowledge about sports-related concussion: is the message getting through to
      coaches and trainers?
AB  - AIM: The need for accurate diagnosis and appropriate return-to-play decisions
      following a concussion in sports has prompted the dissemination of guidelines to
      assist managing this condition. This study aimed to assess whether key messages
      within these guidelines are reflected in the knowledge of coaches and sports
      trainers involved in community sport. METHODS: An online knowledge survey was
      widely promoted across Australia in May-August 2012 targeting community
      Australian Football (AF) and Rugby League (RL) coaches and sports trainers. 260
      AF coaches, 161 AF sports trainers, 267 RL coaches and 228 RL sports trainers
      completed the survey. Knowledge scores were constructed from Likert scales and
      compared across football codes and respondent groups. RESULTS: General concussion
      knowledge did not differ across codes but sports trainers had higher levels than
      did coaches. There were no significant differences in either concussion symptoms
      or concussion management knowledge across codes or team roles. Over 90% of
      respondents correctly identified five of the eight key signs or symptoms of
      concussion. Fewer than 50% recognised the increased risk of another concussion
      following an initial concussion. Most incorrectly believed or were uncertain that
      scans typically show damage to the brain after a concussion occurs. Fewer than
      25% recognised, and >40% were uncertain that younger players typically take
      longer to recover from concussion than adults. CONCLUSIONS: The key messages from
      published concussion management guidelines have not reached community sports
      coaches and sports trainers. This needs to be redressed to maximise the safety of
      all of those involved in community sport.

PMID- 24043667
TI  - Clinical trials in sports physiotherapy. Building on five decades of research to
      produce even better trials: a critical review and tips for improvements.

PMID- 24043669
TI  - Septic nonunions of lower limb long bones: don't neglect Propionibacterium acnes!
AB  - We report 3 clinical cases of septic nonunions of lower limb long bones in which
      the pathogenicity of Propionibacterium acnes was retained after several weeks of
      poor outcome. The patients had fractures that were treated by internal fixation,
      without initially suspected infection. The diagnosis of delayed union coincided
      with the onset of treatment. Support was performed in 2 steps, allowing for the
      collection of several deep samples that were referred for microbiological
      analysis. Molecular techniques for microbiological investigation were performed
      on perioperative samples and were not contributive. The detection of P acnes,
      which was identified after several days of incubation, prompted us to consider
      the role of this bacterium. The presence of P acnes is regularly interpreted as
      contamination of samples during collection or handling in the laboratory. A
      multidisciplinary decision to make the diagnosis of surgical site infection with
      P acnes and specific antibiotic treatment for several months led to consolidation
      in all the patients. The ability of bacteria of the genus Propionibacterium to
      cause insidious surgical site infections should not be underestimated, and more
      extensive sample incubation is essential to diagnose such infections. 

PMID- 24043668
TI  - Collagen XV: exploring its structure and role within the tumor microenvironment.
AB  - The extracellular matrix (ECM) is a critical component of stroma-to-cell
      interactions that subsequently activate intracellular signaling cascades, many of
      which are associated with tumor invasion and metastasis. The ECM contains a wide
      range of proteins with multiple functions, including cytokines, cleaved cell
      surface receptors, secreted epithelial cell proteins, and structural scaffolding.
      Fibrillar collagens, abundant in the normal ECM, surround cellular structures and
      provide structural integrity. However during the initial stages of invasive
      cancers, the ECM is among the first compartments to be compromised. Also present
      in the normal ECM is the nonfibrillar collagen XV, which is seen in the basement
      membrane zone but is lost prior to tumor metastasis in several organs. In
      contrast, the tumor microenvironment often exhibits increased synthesis of
      fibrillar collagen I and collagen IV, which are associated with fibrosis. The
      unique localization of collagen XV and its disappearance prior to tumor invasion
      suggests a fundamental role in maintaining basement membrane integrity and
      preventing the migration of tumor cells across this barrier. This review examines
      the structure of collagen XV, its functional domains, and its involvement in cell
      surface receptor-mediated signaling pathways, thus providing further insight into
      its critical role in the suppression of malignancy.

PMID- 24043670
TI  - Ascending infection of foot tendons in diabetic patients.
AB  - Bone and soft tissue infection in the foot of diabetic patients is a well
      described issue in the literature. A sound anatomical knowledge of the foot
      anatomy and compartments is mandatory to understand the mechanisms of infection
      spread. We describe four cases of diabetic foot infection complicated by long
      ascending infection. All did not respond initially to antibiotic treatment and
      the usual surgical debridement and were cured only after excision of the infected
      tendons. We highlight a rare but serious complication of the diabetic foot
      disease not commonly seen by the surgical community. We hope that this report
      raises the awareness of this condition so that a prompt diagnosis is made and
      appropriate treatment started, thereby reducing the risk of major lower limb
      amputations. 

PMID- 24043671
TI  - A functional single nucleotide polymorphism -1562C>T in the matrix
      metalloproteinase-9 promoter is associated with type 2 diabetes and diabetic foot
      ulcers.
AB  - Impaired neovascularization is the hallmark of type 2 diabetes, which results in
      various macro- and microvascular complications and the development of foot
      ulcerations later in life. Matrix metalloproteinases (MMPs) are the key enzymes
      which influence matrix remodeling. Here, we aim to investigate that whether
      single nucleotide polymorphism (SNP -1562C>T) (rs3918242) in the promoter region
      of MMP-9 gene, which alters the transcriptional activity of MMP-9 is associated
      with type 2 diabetes and diabetic foot ulcers (DFUs). This case-control study was
      composed of 730 individuals, out of which 463 patients were with type 2 diabetes
      mellitus (T2DM) and 267 were nondiabetic healthy controls (non-DM controls). T2DM
      patients were subclassified as 149 cases without any secondary complications
      (T2DMNSC), 110 with DFUs, 204 T2DM patients having one or the other secondary
      complications. Genotyping for -1562C>T SNP in MMP-9 gene was done by polymerase
      chain reaction-restriction fragment length polymorphism method and sequencing.
      SNP -1562C>T of MMP-9 gene showed a significant association with T2DM and DFU.
      The allele distribution differed significantly between patients and normal
      control group (odds ratio = 1.82, P = .00005, 95% confidence interval = 1.36-2.42
      for T2DM vs control and odds ratio = 2.112, P = .00048, 95% confidence interval =
      1.38-3.126 for DFU vs control) indicating strong association of SNP -1562C>T of
      MMP-9 gene with T2DM and DFU in an Indian population. SNP -1562C>T in the
      promoter of the MMP-9 gene results in increased expression at the level of the
      transcription. To the best of our knowledge, this is the first report that
      suggests that SNP -1562C>T in the promoter of the MMP-9 gene is associated with
      T2DM and DFU. An increased MMP-9 production from high expressing T allele may
      promote matrix degradation. 

PMID- 24043672
TI  - Deep vein thrombosis after total hip arthroplasty and total knee arthroplasty in
      patients with previous ischemic stroke.
AB  - The present study evaluated the prevalence and therapy of deep vein thrombosis
      (DVT) after total hip arthroplasty (THA) and total knee arthroplasty (TKA) in 57
      patients with previous ischemic stroke. Postoperative anticoagulants were used
      for DVT prophylaxis, and batroxobin and prolonged anticoagulants were used for
      thrombolysis in DVT subjects. The incidence of DVT after THA and TKA in patients
      with previous ischemic stroke was 16.2% and 20%, respectively. No bleeding
      complications were observed and no new ischemic stroke occurred during the
      following 3 months. The prevalence DVT after THA and TKA in patients with
      previous ischemic stroke was not specific, and the treatment of DVT with
      batroxobin and anticoagulants was effective and safe. 

PMID- 24043673
TI  - Umbilical cord mesenchymal stem cell transplantation ameliorates burn-induced
      acute kidney injury in rats.
AB  - Excessive systemic inflammation following burns could lead to acute kidney injury
      (AKI). Mesenchymal stromal cells (MSCs) suppress immune cell responses and have
      beneficial effects in various inflammatory-related immune disorders. However,
      autologous MSCs are not vital enough for the treatment because of the severely
      burned patients' deleterious condition. Umbilical cord-derived mesenchymal stem
      cells (UC-MSCs) could be a suitable substitute cell candidate but no data are
      available on the therapeutic effectiveness of UC-MSCs transplantation for burn
      injury and its consequences. In this study, UC-MSCs or ulinastatin was
      administered intravenously in the rats with burn trauma, and the therapeutic
      effects of UC-MSCs on the survival of severe burn-induced AKI rats and functional
      protection of kidney were analyzed. Results showed that UC-MSCs promoted the
      survival and prevented commitment to apoptosis of resident kidney cells and
      reduced organ microscopic damage in kidneys after thermal trauma. Thus, our study
      demonstrates that intravenously delivered UC-MSCs protected the host from death
      caused by kidney injury subsequent to severe burn, identifying UC-MSCs
      transplantation may be an attractive candidate for cell-based treatments for
      burns and induced organ damage. 

PMID- 24043674
TI  - Shewanella putrefaciens, a rare cause of osteomyelitis.
AB  - Shewanella putrefaciens is a Gram-negative bacillus with a distinguishable
      characteristic of hydrogen sulfide production and routinely found in a marine
      environment. This organism has been cultured as a pathogen in a small number of
      soft tissue infections, but has rarely been the causative agent in osteomyelitis.
      This case report details calcaneal osteomyelitis due to S putrefaciens in a 77
      year-old male with bilateral heel ulcerations and peripheral vascular disease. 

PMID- 24043675
TI  - Case series of isolated primary persistent sciatic vein.
AB  - Our study aimed to present a short series on the persistent sciatic vein, a rare
      venous variation, without Klippel-Trenaunay-Weber syndrome and to review the
      anatomical consideration of deep venous systems. Four cases of lower-type
      persistent sciatic vein were found. A combination of May-Thurner syndrome and
      persistent sciatic vein was found in 2 cases. Non-hypoplastic femoral veins,
      normal and duplicated, were found in 3 cases. This study concluded that in this
      persistent sciatic vein, the associated non-hypoplastic femoral vein is not
      uncommon, and care must be taken about this condition during ultrasonographic
      examination. Unusual causes of chronic venous insufficiency and other venous
      anomalies should not be overlooked. 

PMID- 24043676
TI  - Vascular nursing in Greece: luxury or necessity?
AB  - Although peripheral arterial disease is prevalent in the primary care setting,
      insufficient vascular education among nurses and physicians coupled with certain
      economic constraints undermines treatment efficacy. Moreover, the burden of
      advanced venous pathology such as posthrombotic syndrome, venous ulcers, and
      lymphedema remains suboptimally treated. This article advocates the development
      of a vascular nursing specialty as a means to improving vascular care especially
      nowadays, when health care providers dictate comprehensive and cost-effective
      nursing practice and patient management. It also presents the first attempt to
      organize a Vascular Nursing Educational Session in Greece. 

PMID- 24043677
TI  - The clinical effectiveness of two compression stocking treatments on venous leg
      ulcer recurrence: a randomized controlled trial.
AB  - Venous leg ulcers affect up to 3% of people aged 65 years and older, present
      significant pain and suffering, and are associated with long episodes of health
      care. These chronic wounds recur at rates of up to 69%. A double blind randomized
      controlled trial was conducted in a home nursing setting in Victoria, Australia
      to compare the effectiveness of a 23 to 32 mm Hg (moderate) and a 34 to 46 mm Hg
      (high) compression stocking treatment on venous ulcer recurrence. Participants (n
      = 100) were monitored for 26 weeks. Study wound recurrence was low (11.8%), and
      the average time to recurrence was 77.91 days. Adherence to treatment was low
      (44%) with nonadherence significantly higher in the high-compression stocking
      group, chi(2)(1) = 8.827, P = .003. Regression modeling found that adherence to
      treatment significantly predicted study wound recurrence, Wald(1) = 7.917, P =
      .005. Estimated hazard ratios showed that participants who did not adhere were 9
      times more likely to have their wound recur. Risk of recurrence was 3 times
      greater for those randomized to moderate compression when compared with the high
      compression stocking. Implementing strategies that optimize adherence to
      compression will reduce ulcer recurrence. Once this has been realized, the
      potential to adhere to high-compression treatment would further reduce the risk
      of recurrence. 

PMID- 24043678
TI  - Repair of pretibial atonic wound with long cross-leg flap.
AB  - Soft-tissue defects of the pretibial region constitute a major reconstructive
      challenge because of the insufficiency of the local tissues. In such cases, a
      long cross-leg flap may be an alternative option. This study presents a case with
      an atonic wound in the pretibial region caused by a previous traffic accident,
      which had received cross-leg flap repair following the excision. 

PMID- 24043679
TI  - Macrophage activation dysfunction in impaired wound healing: a potential
      therapeutic target.

PMID- 24043680
TI  - Influence of the location of nonischemic diabetic forefoot osteomyelitis on time
      to healing after undergoing surgery.
AB  - The forefoot has been reported as the most frequent location of osteomyelitis in
      the feet of patients with diabetes. The forefoot includes toes and metatarsal
      heads as common locations of bone infections, but the anatomy of these bones is
      quite different. As a result, such differences in anatomy may have an impact on
      the outcomes. The aim of the present study was to determine whether different
      locations of osteomyelitis in the forefoot have any influence on time to healing
      after undergoing surgery in a prospective series including 195 patients without
      peripheral arterial disease and osteomyelitis confirmed by histopathology.
      Location of the lesion was classified into 4 groups: hallux, first metatarsal
      head, lesser metatarsal heads, and lesser toes. The time required to achieve
      healing and the cumulative rate of wounds healed and likelihood of healing were
      analyzed at 4, 8, and 12 weeks after surgery. Time of healing (mean +/- SD) in
      the whole series was 10.7 +/- 8.4 weeks. Osteomyelitis located in the lesser toes
      has a higher probability of healing by the fourth week (odds ratio [OR] = 5.7,
      95% confidence interval [CI] = 2.8-11.6, P < .001), eighth week (OR = 3.2, 95% CI
      = 1.6-6.4, P < .001), or twelfth week (OR = 3.1, 95% CI = 1.3-7.0, P = .008) than
      other osteomyelitis locations. Osteomyelitis located in the first metatarsal
      joint was less likely to heal by the eighth week (OR = 0.4, 95% CI = 0.2-0.9, P =
      .037) and 12th week (OR = 0.4, 95% CI = 0.2-1.0, P = .040). In conclusion, time
      to healing is significantly different according to the location of the bone
      infection in the forefoot. 

PMID- 24043681
TI  - Heel ulcer and blood flow: the importance of the angiosome concept.
AB  - A young female diabetic patient is reported, who presented with a double foot
      lesion. She presented with a first metatarsal head exposure concomitant with a
      heel wet gangrene. Magnetic resonance demonstrated osteomyelitis of the rear
      portion of the calcaneus. Transmetatarsal amputation was performed and a wide
      debridement was required to remove all gangrenous tissue from the heel wound. The
      pedal artery was palpable; the posterior tibial pulse was present, but
      weak.Transcutaneous oximetry (TcPO2) at the dorsum of the foot was TcPO2 = 56
      mmHg despite significant oedema. Nevertheless, TcPO2 on the perilesional area of
      the heel ulcer (TcPO2 = 24mmHg) was suggestive for critical chronic ischemia. At
      angiographic examination, anterior tibial and peroneal arteries were patent, but
      the posterior tibial artery that showed severe stenosis then percutaneous
      angioplasty (PTA) was performed. Just the day after PTA, values of TcPO2 at the
      perilesional area of the heel ulcer increased to 41 mmHg. Heel osteomyelitis was
      subsequently treated by partial calcanectomy. The patient was discharged after a
      21-day hospital stay. In the treatment of heel ulcers, it is clinically useful to
      use the angiosomic concept. The majority of the blood supply to the heel is
      provided by the posterior tibial artery, and only to a small extent by the
      posterior branch of peroneal artery. If the decrease in blood flow to this region
      is not detected, and direct flow based on the angiosome concept is not obtained,
      the healing of a heel ulcer may be delayed or impaired. 

PMID- 24043682
TI  - Update on the inaugural Sydney Diabetic Foot Conference 2013.
AB  - The first International Diabetic Foot Conference in Australia was hosted at
      Liverpool Hospital in Sydney during May 30-31, 2013. In response to the growing
      diabetes epidemic globally and more locally to Australia, the conference provided
      the perfect bridge for interaction between the multidisciplinary team members
      involved in diabetes care and the opportunity to assimilate the most up-to-date
      evidence-based medicine from some of the most respected researchers in the field.

PMID- 24043683
TI  - Unilateral livedoid vasculopathy associated with involutional phase of cutaneous
      infantile hemangioma: the connection to coagulation disorders.
AB  - Livedoid vasculopathy is a bilateral painful and recurrent cutaneous ulcerative
      disorder of the legs that leads to atrophie blanche, atrophic white-porcelain
      scars, and is associated with disorders of fibrinolysis and/or coagulation. We
      present a young boy with an association between livedoid vasculopathy in the area
      of a previous involuted cutaneous hemangioma. We found 4 uncommon abnormalities
      associated with thrombo-occlusive events: heterozygous 20210 A->G genotype of
      prothrombin, reduced activity of anticoagulation proteins C and S, and elevated
      lipoprotein (a). 

PMID- 24043684
TI  - Motorcycle muffler-induced "pillion burns" of distal leg: a persistent problem of
      increasing proportions in Indian settings.
AB  - Motorcycles have emerged as a viable mode of transport for millions in the third
      world. Mufflers (exhaust pipes in some countries) remain a potential "Achilles'
      tendon" or a designing flaw in the mass-produced, economical motorcycles of the
      developing world. Owing to the excessive temperature they attain while the hot
      exhaust gases pass through them and their proximity to the lower limbs while
      riding a motorcycle, they can lead to burns of varying nature in the lower leg.
      This is a descriptive retrospective study of muffler-induced lower leg burns
      treated at our hospital from January 2008 to December 2012. Various parameters
      including history, exact mode of injury, age, sex, degree and location of burn,
      treatment modalities, and other relevant circumstantial/logistical factors
      associated with such injuries were noted; data were tabulated and statistically
      arranged to gain an insight into this problem. Possible interventions that may
      help avoid such injuries are also briefly mentioned. Certain findings that are
      quite distinct to the findings of a few earlier studies carried out on this topic
      (in the developed world) remain the highlight of our study. The typical muffler
      induced burns in the Indian setting occur almost exclusively in the male
      pillions, most of the times in the right leg in an area near the medial
      malleolus, and are usually second degree and respond to conservative management.
      Prompt treatment can circumvent much of the dreaded complications. Preemptive
      efforts in designing of motorcycles and following traffic regulations at the
      individual level remain the key to prevention.

PMID- 24043685
TI  - Topical application of silver nitrate.

PMID- 24043686
TI  - Plague gives surprises in the first decade of the 21st century in the United
      States and worldwide.
AB  - Plague is an ancient disease caused by the bacterium Yersinia pestis and
      transmitted by rodent flea bites that continues to surprise us with first-ever
      events. This review documents plague in human cases in the 1st decade of the 21st
      century and updates our knowledge of clinical manifestations, transmission during
      outbreaks, diagnostic testing, antimicrobial treatment, and vaccine development.
      In the United States, 57 persons were reported to have the disease, of which
      seven died. Worldwide, 21,725 persons were affected with 1,612 deaths, for a case
      fatality rate of 7.4%. The Congo reported more cases than any other country,
      including two large outbreaks of pneumonic plague, surpassing Madagascar, which
      had the most cases in the previous decade. Two United States scientists suffered
      fatal accidental exposures: a wildlife biologist, who carried out an autopsy on a
      mountain lion in Arizona in 2007, and a geneticist with subclinical
      hemochromatosis in Chicago, who was handling an avirulent strain of Y. pestis in
      2009. Antimicrobial drugs given early after the onset of symptoms prevented many
      deaths; those recommended for treatment and prophylaxis included gentamicin,
      doxycycline, and fluoroquinolones, although fluoroquinolones have not been
      adequately tested in humans. Fleas that do not have their guts blocked by clotted
      blood meals were shown to be better transmitters of plague than blocked fleas.
      Under development for protection against bioterrorist use, a subunit vaccine
      containing F1 and V antigens of Y. pestis was administered to human volunteers
      eliciting antibodies without any serious side effects. These events, although
      showing progress, suggest that plague will persist in rodent reservoirs mostly in
      African countries burdened by poverty and civil unrest, causing death when
      patients fail to receive prompt antimicrobial treatment.

PMID- 24043687
TI  - Field detection of Tembusu virus in western Thailand by rt-PCR and vector
      competence determination of select culex mosquitoes for transmission of the
      virus.
AB  - Tembusu virus (TMUV; Ntaya serocomplex) was detected in two pools of mosquitoes
      captured near Sangkhlaburi, Thailand, as well as from sera from sentinel ducks
      from the same area. Although TMUV has been isolated from several mosquito species
      in Asia, no studies have ever shown competent vectors for this virus. Therefore,
      we allowed mosquitoes captured near Sangkhlaburi to feed on young chickens that
      had been infected with TMUV. These mosquitoes were tested approximately 2 weeks
      later to determine infection, dissemination, and transmission rates. Culex
      vishnui developed high viral titers after feeding on TMUV-infected chicks and
      readily transmitted virus to naive chickens. In contrast, Cx. fuscocephala seemed
      less susceptible to infection, and more importantly, zero of five fuscocephala
      with a disseminated infection transmitted virus by bite, indicating a salivary
      gland barrier. These results provide evidence for the involvement of Culex
      mosquitoes in the transmission of TMUV in the environment.

PMID- 24043688
TI  - Diagnostic value of culture and serological tests in the diagnosis of
      histoplasmosis in HIV and non-HIV Colombian patients.
AB  - We determined the value of culture and serological tests used to diagnose
      histoplasmosis. The medical records of 391 histoplasmosis patients were analyzed.
      Diagnosis of the mycosis was assessed by culture, complement fixation, and
      immunodiffusion tests; 310 patients (79.5%) were male, and 184 patients (47.1%)
      were infected with human immunodeficiency virus (HIV). Positivity value for
      cultures was 35.7% (74/207), reactivity of serological tests was 95.2% (160/168),
      and a combination of both methodologies was 16.9% (35/207) for non-HIV patients.
      Positivity value for cultures was 75.0% (138/184), reactivity of serological
      tests was 92.4% (85/92), and a combination of both methodologies was 26.0%
      (48/184) for HIV/acquired immunodeficiency syndrome (AIDS) patients; 48.1%
      (102/212) of extrapulmonary samples from HIV/AIDS patients yielded positive
      cultures compared with 23.1% (49/212) in non-HIV patients. Lymphocyte counts made
      for 33.1% (61/184) of HIV/AIDS patients showed a trend to low CD4+ numbers and
      higher proportion of positive cultures. These results indicate that culture is
      the most reliable fungal diagnostic method for HIV/AIDS patients, and contrary to
      what is generally believed, serological assays are useful for diagnosing
      histoplasmosis in these patients.

PMID- 24043689
TI  - Regression of severe tungiasis-associated morbidity after prevention of re
      infestation: a case series from rural Madagascar.
AB  - Tungiasis (sand flea disease) is a neglected tropical disease. Heavy infestation
      results in mutilation of the feet and difficulty in walking. We identified eight
      individuals with extremely severe tungiasis in rural Madagascar. To prevent
      reinfestation, four individuals received solid shoes and four received a daily
      application of an herbal repellent effective against Tunga penetrans. Over a
      period of 10 weeks the feet were examined and the severity of tungiasis
      associated morbidity was measured. Within this period, the severity score for
      acute tungiasis decreased 41% in the shoe group and 89% in the repellent group.
      The four major inflammation-related symptoms disappeared in the four patients of
      the repellent group, but only in two patients of the shoe group. Those
      observations indicate that cases with extremely severe tungiasis, associated
      morbidity almost totally disappears within 10 weeks if the feet are protected by
      a repellent. Wearing shoes reduced acute morbidity only marginally.

PMID- 24043690
TI  - Phenotypic variation among Culex pipiens complex (Diptera: Culicidae) populations
      from the Sacramento Valley, California: horizontal and vertical transmission of
      West Nile virus, diapause potential, autogeny, and host selection.
AB  - The vector competence and bionomics of Culex pipiens form pipiens L. and Cx.
      pipiens f. molestus Forskal were evaluated for populations from the Sacramento
      Valley. Both f. pipiens and f. molestus females became infected, produced
      disseminated infections, and were able to transmit West Nile virus. Form molestus
      females also transmitted West Nile virus vertically to egg rafts and F1 progeny,
      whereas f. pipiens females only transmitted to egg rafts. Culex pipiens complex
      from urban Sacramento blood-fed on seven different avian species and two
      mammalian species. Structure analysis of blood-fed mosquitoes identified K = 4
      genetic clusters: f. molestus, f. pipiens, a group of genetically similar hybrids
      (Cluster X), and admixed individuals. When females were exposed as larvae to
      midwinter conditions in bioenvironmental chambers, 85% (N = 79) of aboveground
      Cx. pipiens complex females and 100% (N = 34) of underground f. molestus females
      did not enter reproductive diapause.

PMID- 24043691
TI  - Dried blood spots for qPCR diagnosis of acute Bartonella bacilliformis infection.
AB  - Bartonella bacilliformis is the etiological agent of a life-threatening illness.
      Thin blood smear is the most common diagnostic method for acute infection in
      endemic areas of Peru but remains of limited value because of low sensitivity.
      The aim of this study was to adapt a B. bacilliformis-specific real-time
      polymerase chain reaction (PCR) assay for use with dried blood spots (DBS) as a
      sampling method and assess its performance and use for the diagnosis and
      surveillance of acute Bartonella infection. Only two of 65 children (3%) that
      participated in this study had positive blood smears for B. bacilliformis,
      whereas 16 (including these two) were positive by PCR performed on DBS samples
      (24.6%). The use of DBS in combination with B. bacilliformis-specific PCR could
      be a useful tool for public health in identifying and monitoring outbreaks of
      infection and designing control programs to reduce the burden of this life
      threatening illness.

PMID- 24043692
TI  - Seroepidemiologic survey for Coxiella burnetii among US military personnel
      deployed to Southwest and Central Asia in 2005.
AB  - We used a seroepidemiologic study to estimate Q fever (Coxiella burnetii)
      seroprevalence, seroincidence, and risk factors for seroconversion in two
      deployed military populations in 2005. The first study group resided in an area
      with a known Q fever outbreak history (Al Asad, Iraq). Of this population, 7.2%
      seroconverted for an incidence rate of 10.6 seroconversions per 1,000 person
      months. The second population included personnel transiting through Qatar on mid
      deployment leave from southwest/central Asia. In this group, we found 2.1%
      prevalence with 0.92 seroconversions per 1,000 person-months. However, no
      significant risk factors for Q fever seroconversion were found in either
      population.

PMID- 24043693
TI  - High levels of extended-spectrum beta-lactamases in a major teaching hospital in
      Ghana: the need for regular monitoring and evaluation of antibiotic resistance.
AB  - Infections with bacteria producing extended-spectrum beta-lactamases (ESBLs) are
      increasing across Africa. This study reports on ESBL-producing Enterobacteriaceae
      as significant causes of infections and antibiotic resistance at Korle-Bu
      Teaching Hospital in Accra, Ghana. Of 300 isolates examined, 49.3% produced
      ESBLs. The prevalence of ESBLs was significantly high among isolates from
      neonates (28 of 43, 65.1%; relative risk = 1.62, 95% confidence interval = 1.33
      2.13, P = 0.002) and adult patients > 65 years of age (36 of 51, 70.5%; relative
      risk = 1.89, 95% confidence interval = 1.41-2.40, P = 0.001). A marked increase
      in minimum inhibitory concentrations of ESBL-positive species was noticed
      compared with those for the other strains. Using these concentrations, we found
      that 26 (17%) ESBL producers were resistant to two or more antibiotics
      (aminoglycosides, fluoroquinolones, sulfonamide, and carbapenems) whereas 5
      (3.2%) non-ESBL producers were multidrug resistant. Regular ESBL detection and
      evaluation of antibiotic resistance may help reduce the spread of ESBLs and
      antibiotic resistance in Ghana.

PMID- 24043695
TI  - Expression and function of cyclooxygenase-2 is necessary for hamster blastocyst
      hatching.
AB  - Blastocyst hatching is critical for successful implantation leading to pregnancy.
      Its failure causes infertility. The phenomenon of blastocyst hatching in humans
      is poorly understood and the available information on this stems from studies of
      rodents such as mice and hamsters. We and others showed that hamster blastocyst
      hatching is characterized by firstly blastocyst deflation followed by a
      dissolution of the zona pellucida (zona) and accompanied by trophectodermal
      projections (TEPs). We also showed that embryo-derived cathepsins (Cat)
      proteases, specifically Cat-L, -B and -P act as zonalysins and are responsible
      for hatching. In this study, we show the expression and function of one of the
      potential regulators of embryogenesis, cyclooxygenase (COX)-2 during blastocyst
      development and hatching. The expression of COX-2 mRNA and protein was observed
      in 8-cell through hatched blastocyst stages and it was also localized to
      blastocyst's TEPs. Specific COX-2 inhibitors, NS-398 and CAY-10404, inhibited
      blastocyst hatching; percentages achieved were only 28.4 +/- 5.3 and 32.3 +/-
      5.4%, respectively, compared with >90% with untreated embryos. Interestingly,
      inhibitor-treated blastocysts failed to deflate, normally observed during
      hatching. Supplementation of prostaglandins (PGs)-E2 or -I2 to cultured embryos
      reversed the inhibitors' effect on hatching and also the deflation behavior.
      Importantly, the levels of mRNA and protein of Cat-L, -B and -P showed a
      significant reduction in the inhibitor-treated embryos compared with untreated
      embryos, although its mechanism remains to be examined. These data provide the
      first evidence that COX-2 is critical for blastocyst hatching in the golden
      hamster. 

PMID- 24043696
TI  - TGFbeta1 and SGK1-sensitive store-operated Ca2+ entry and Orai1 expression in
      endometrial Ishikawa cells.
AB  - The serum-and-glucocorticoid-inducible-kinase-1 (SGK1) is ubiquitously expressed
      and under genomic control by cell stress, hormones and further mediators. A most
      powerful stimulator of SGK1 expression is transforming growth factor TGFbeta1.
      SGK1 is activated by insulin and growth factors via phosphatidylinositol-3-kinase
      and the 3-phosphoinositide-dependent kinase PDK1. As shown recently, SGK1
      increases the store-operated Ca(2+) entry (SOCE), which is accomplished by the
      pore-forming ion channel unit Orai. Most recent observations further revealed
      that SGK1 plays a critical role in the regulation of fertility. SGK1 is up
      regulated in the luminal epithelium of women with unexplained infertility but
      down-regulated in decidualizing stromal cells of patients with recurrent
      pregnancy loss. The present study explored whether Orai1 is expressed in
      endometrium and sensitive to regulation by SGK1 and/or TGFbeta1. To this end,
      Orai1 protein abundance was determined by western blotting and SOCE by fura-2
      fluorescence. As a result, Orai1 was expressed in human endometrium and in human
      endometrial Ishikawa cells. Orai1 expression and SOCE in Ishikawa cells were
      increased by transfection with constitutively active (S422D)SGK1 but not by
      transfection with inactive (K127N)SGK1. The difference of SOCE between
      (S422D)SGK1 and (K127N)SGK1-transfected cells was virtually abrogated in the
      presence of Orai1 inhibitor 2-aminoethoxydiphenyl borate (2-APB, 50 uM). Similar
      to (S422D)SGK1 transfection TGFbeta1 treatment up-regulated both Orai1 protein
      abundance and SOCE. In conclusion, Orai1 is expressed in the human endometrium
      and is up-regulated by SGK1 and TGFbeta1. The present observations thus uncover a
      novel element in SGK1-sensitive regulation of endometrial cells. 

PMID- 24043697
TI  - Frances Brodsky: so you think you know all about clathrin? Interview by Caitlin
      Sedwick.

PMID- 24043694
TI  - The role of glycans in immune evasion: the human fetoembryonic defence system
      hypothesis revisited.
AB  - Emerging data suggest that mechanisms to evade the human immune system may be
      shared by the conceptus, tumour cells, persistent pathogens and viruses. It is
      therefore timely to revisit the human fetoembryonic defense system (Hu-FEDS)
      hypothesis that was proposed in two papers in the 1990s. The initial paper
      suggested that glycoconjugates expressed in the human reproductive system
      inhibited immune responses directed against gametes and the developing human by
      employing their carbohydrate sequences as functional groups. These
      glycoconjugates were proposed to block specific binding interactions and interact
      with lectins linked to signal transduction pathways that modulated immune cell
      functions. The second article suggested that aggressive tumour cells and
      persistent pathogens (HIV, H. pylori, schistosomes) either mimicked or acquired
      the same carbohydrate functional groups employed in this system to evade immune
      responses. This subterfuge enabled these pathogens and tumour cells to couple
      their survival to the human reproductive imperative. The Hu-FEDS model has been
      repeatedly tested since its inception. Data relevant to this model have also been
      obtained in other studies. Herein, the Hu-FEDS hypothesis is revisited in the
      context of these more recent findings. Far more supportive evidence for this
      model now exists than when it was first proposed, and many of the original
      predictions have been validated. This type of subterfuge by pathogens and tumour
      cells likely applies to all sexually reproducing metazoans that must protect
      their gametes from immune responses. Intervention in these pathological states
      will likely remain problematic until this system of immune evasion is fully
      understood and appreciated. 

PMID- 24043698
TI  - pHocal adhesion kinase regulation is on a FERM foundation.
AB  - Increases in intracellular pH (pHi) occur upon integrin receptor binding to
      matrix proteins and in tumor cells. In this issue, Choi et al. (2013. J. Cell
      Biol. http://dx.doi.org/10.1083/jcb.201308034) show that pHi increase activates
      FAK by causing deprotonation of histidine 58 in its FERM (band 4.1, ezrin,
      radixin, moesin) homology domain, which exposes a region important for FAK
      autophosphorylation. This model of FAK activation could contribute to motility of
      tumor cells by promoting focal adhesion turnover. 

PMID- 24043700
TI  - pH sensing by FAK-His58 regulates focal adhesion remodeling.
AB  - Intracellular pH (pHi) dynamics regulates diverse cellular processes, including
      remodeling of focal adhesions. We now report that focal adhesion kinase (FAK), a
      key regulator of focal adhesion remodeling, is a pH sensor responding to
      physiological changes in pH. The initial step in FAK activation is
      autophosphorylation of Tyr397, which increased with higher pHi. We used a
      genetically encoded biosensor to show increased pH at focal adhesions as they
      mature during cell spreading. We also show that cells with reduced pHi had
      attenuated FAK-pY397 as well as defective cell spreading and focal adhesions.
      Mutagenesis studies indicated FAK-His58 is critical for pH sensing and molecular
      dynamics simulations suggested a model in which His58 deprotonation drives
      conformational changes that may modulate accessibility of Tyr397 for
      autophosphorylation. Expression of FAK-H58A in fibroblasts was sufficient to
      restore defective autophosphorylation and cell spreading at low pHi. These data
      are relevant to understanding cancer metastasis, which is dependent on increased
      pHi and FAK activity. 

PMID- 24043699
TI  - Cell biology in neuroscience: Cellular and molecular mechanisms underlying axon
      formation, growth, and branching.
AB  - Proper brain wiring during development is pivotal for adult brain function.
      Neurons display a high degree of polarization both morphologically and
      functionally, and this polarization requires the segregation of mRNA, proteins,
      and lipids into the axonal or somatodendritic domains. Recent discoveries have
      provided insight into many aspects of the cell biology of axonal development
      including axon specification during neuronal polarization, axon growth, and
      terminal axon branching during synaptogenesis. 

PMID- 24043701
TI  - Ero1-alpha and PDIs constitute a hierarchical electron transfer network of
      endoplasmic reticulum oxidoreductases.
AB  - Ero1-alpha and endoplasmic reticulum (ER) oxidoreductases of the protein
      disulfide isomerase (PDI) family promote the efficient introduction of disulfide
      bonds into nascent polypeptides in the ER. However, the hierarchy of electron
      transfer among these oxidoreductases is poorly understood. In this paper, Ero1
      alpha-associated oxidoreductases were identified by proteomic analysis and
      further confirmed by surface plasmon resonance. Ero1-alpha and PDI were found to
      constitute a regulatory hub, whereby PDI induced conformational flexibility in an
      Ero1-alpha shuttle cysteine (Cys99) facilitated intramolecular electron transfer
      to the active site. In isolation, Ero1-alpha also oxidized ERp46, ERp57, and P5;
      however, kinetic measurements and redox equilibrium analysis revealed that PDI
      preferentially oxidized other oxidoreductases. PDI accepted electrons from the
      other oxidoreductases via its a' domain, bypassing the a domain, which serves as
      the electron acceptor from reduced glutathione. These observations provide an
      integrated picture of the hierarchy of cooperative redox interactions among ER
      oxidoreductases in mammalian cells. 

PMID- 24043703
TI  - Salicylic acid induces mitochondrial injury by inhibiting ferrochelatase heme
      biosynthesis activity.
AB  - Salicylic acid is a classic nonsteroidal anti-inflammatory drug. Although
      salicylic acid also induces mitochondrial injury, the mechanism of its
      antimitochondrial activity is not well understood. In this study, by using a one
      step affinity purification scheme with salicylic acid-immobilized beads,
      ferrochelatase (FECH), a homodimeric enzyme involved in heme biosynthesis in
      mitochondria, was identified as a new molecular target of salicylic acid.
      Moreover, the cocrystal structure of the FECH-salicylic acid complex was
      determined. Structural and biochemical studies showed that salicylic acid binds
      to the dimer interface of FECH in two possible orientations and inhibits its
      enzymatic activity. Mutational analysis confirmed that Trp301 and Leu311,
      hydrophobic amino acid residues located at the dimer interface, are directly
      involved in salicylic acid binding. On a gel filtration column, salicylic acid
      caused a shift in the elution profile of FECH, indicating that its conformational
      change is induced by salicylic acid binding. In cultured human cells, salicylic
      acid treatment or FECH knockdown inhibited heme synthesis, whereas salicylic acid
      did not exert its inhibitory effect in FECH knockdown cells. Concordantly,
      salicylic acid treatment or FECH knockdown inhibited heme synthesis in zebrafish
      embryos. Strikingly, the salicylic acid-induced effect in zebrafish was partially
      rescued by FECH overexpression. Taken together, these findings illustrate that
      FECH is responsible for salicylic acid-induced inhibition of heme synthesis,
      which may contribute to its antimitochondrial and anti-inflammatory function.
      This study establishes a novel aspect of the complex pharmacological effects of
      salicylic acid. 

PMID- 24043702
TI  - Biocompatible fluorescent silicon nanocrystals for single-molecule tracking and
      fluorescence imaging.
AB  - Fluorescence microscopy is used extensively in cell-biological and biomedical
      research, but it is often plagued by three major problems with the presently
      available fluorescent probes: photobleaching, blinking, and large size. We have
      addressed these problems, with special attention to single-molecule imaging, by
      developing biocompatible, red-emitting silicon nanocrystals (SiNCs) with a 4.1-nm
      hydrodynamic diameter. Methods for producing SiNCs by simple chemical etching,
      for hydrophilically coating them, and for conjugating them to biomolecules
      precisely at a 1:1 ratio have been developed. Single SiNCs neither blinked nor
      photobleached during a 300-min overall period observed at video rate. Single
      receptor molecules in the plasma membrane of living cells (using transferrin
      receptor) were imaged for >=10 times longer than with other probes, making it
      possible for the first time to observe the internalization process of receptor
      molecules at the single-molecule level. Spatial variations of molecular
      diffusivity in the scale of 1-2 um, i.e., a higher level of domain mosaicism in
      the plasma membrane, were revealed. 

PMID- 24043704
TI  - Comparison of immune and health markers in intact and neonatally castrated male
      pigs.
AB  - Stress and sex hormones are known to regulate immune function. Castration of male
      piglets is used to avoid boar taint in the meat, but its consequences on immunity
      and health of male pigs are poorly known. In this study, intact and neonatally
      surgically castrated male pigs (n=20 per group) were compared along puberty for
      some immune parameters and hormone receptor expression in lymphoid organs. Pigs
      were immunised with keyhole limpet haemocyanin (KLH) at 113 and 133 days of age.
      Blood lymphocyte numbers and proliferation, immunoglobulin titres, haptoglobin
      and hormone levels at 89, 119 and 152 days and the mRNA expression of androgen,
      alpha-oestrogen, glucocorticoid and beta2-adrenergic receptors in liver, spleen
      and thymus at 160 days were assessed. Blood lymphocyte numbers were lower (at 119
      and 152 days) and total IgG and haptoglobin concentrations were higher (at 152
      days) in castrated than intact males. The concanavalin A and KLH proliferation
      responses and anti-KLH IgG titres were not altered. At slaughter, intact pigs
      presented a heavier thymus and a lower hepatic expression of beta2-adrenergic
      receptor. In conclusion, the effects of neonatal castration were moderate. Other
      studies are needed to clarify the possible detrimental outcomes of castration on
      lymphocyte numbers and thymic growth. 

PMID- 24043705
TI  - Report of the first veterinary student support workshop.

PMID- 24043706
TI  - Tools and interventions for offenders: where do we go next?

PMID- 24043707
TI  - Young swimmers' classification based on kinematics, hydrodynamics, and
      anthropometrics.
AB  - The aim of this article has been to classify swimmers based on kinematics,
      hydrodynamics, and anthropometrics. Sixty-seven young swimmers made a maximal 25
      m front-crawl to measure with a speedometer the swimming velocity (v), speed
      fluctuation (dv) and dv normalized to v (dv/v). Another two 25 m bouts with and
      without carrying a perturbation device were made to estimate active drag
      coefficient (CDa). Trunk transverse surface area (S) was measured with
      photogrammetric technique on land and in the hydrodynamic position. Cluster 1 was
      related to swimmers with a high speed fluctuation (ie, dv and dv/v), cluster 2
      with anthropometrics (ie, S) and cluster 3 with a high hydrodynamic profile (ie,
      CDa). The variable that seems to discriminate better the clusters was the dv/v
      (F=53.680; P<.001), followed by the dv (F=28.506; P<.001), CDa (F=21.025;
      P<.001), S (F=6.297; P<.01) and v (F=5.375; P=.01). Stepwise discriminant
      analysis extracted 2 functions: Function 1 was mainly defined by dv/v and S
      (74.3% of variance), whereas function 2 was mainly defined by CDa (25.7% of
      variance). It can be concluded that kinematics, hydrodynamics and anthropometrics
      are determinant domains in which to classify and characterize young swimmers'
      profiles.

PMID- 24043708
TI  - Impact of highly active antiretroviral treatment on expression of HIV-1
      coreceptors and ligand levels in peripheral blood from HIV-1 infected patients in
      China.
AB  - OBJECTIVE: Coreceptors are important for HIV-1 entry into target cells and
      disease progression. The impact of HIV-1 and highly active antiretroviral
      treatment (HAART) on coreceptor expression has been little studied. METHODS:
      Expression of C-C chemokine receptor (CCR) 5 and C-X-C chemokine receptor (CXCR)
      4 on CD4+ and CD8 + T cells was compared in HIV-1-infected individuals who
      had/had not received HAART, and in healthy controls. Relationships between
      coreceptors and their chemokine ligands were studied. RESULTS: This study
      included 23 controls and 88 HIV-1-infected individuals, 35 of whom were HAART
      naive. Percentages of CCR5 and CXCR4+ CD8 + T cells were higher, and CXCR4+ CD4 +
      T cells were lower, in patients than in controls. Patients receiving HAART showed
      a higher percentage of CCR5 expression on CD4 + T cells compared with HAART-naive
      patients. HIV-infected individuals had significantly increased levels of
      peripheral ligands for coreceptors, compared with controls; levels were
      significantly higher in those receiving HAART compared with the HAART-naive.
      CONCLUSIONS: HIV-1 infection increases coreceptor expression on T cells; HAART
      increases CCR5 expression further and decreases CXCR4 expression, reversing the
      switch from CCR5 to CXCR4, which was significant for CD4 + T.

PMID- 24043709
TI  - Arabidopsis tic62 trol mutant lacking thylakoid-bound ferredoxin-NADP+
      oxidoreductase shows distinct metabolic phenotype.
AB  - Ferredoxin-NADP+ oxidoreductase (FNR), functioning in the last step of the
      photosynthetic electron transfer chain, exists both as a soluble protein in the
      chloroplast stroma and tightly attached to chloroplast membranes. Surface plasmon
      resonance assays showed that the two FNR isoforms, LFNR1 and LFNR2, are bound to
      the thylakoid membrane via the C-terminal domains of Tic62 and TROL proteins in a
      pH-dependent manner. The tic62 trol double mutants contained a reduced level of
      FNR, exclusively found in the soluble stroma. Although the mutant plants showed
      no visual phenotype or defects in the function of photosystems under any
      conditions studied, a low ratio of NADPH/NADP+ was detected. Since the CO2
      fixation capacity did not differ between the tic62 trol plants and wild-type, it
      seems that the plants are able to funnel reducing power to most crucial reactions
      to ensure survival and fitness of the plants. However, the activity of malate
      dehydrogenase was down-regulated in the mutant plants. Apparently, the plastid
      metabolism is able to cope with substantial changes in directing the electrons
      from the light reactions to stromal metabolism and thus only few differences are
      visible in steady-state metabolite pool sizes of the tic62 trol plants.

PMID- 24043710
TI  - Resolving the activation site of positive regulators in plant phosphoenolpyruvate
      carboxylase.

PMID- 24043711
TI  - Polarity of mature human odontoblasts.
AB  - Odontoblast polarization is based on histological appearance as columnar cells
      with asymmetric disposition of organelles and plasma membrane domains. However,
      little is known about the odontoblast plasma membrane organization. We
      investigated odontoblast membrane polarity using influenza virus hemagglutinin
      and vesicular stomatitis virus glycoprotein as model proteins in mature human
      odontoblast organ culture. We also examined the distribution patterns of
      aquaporin 4 and 5, which are basolateral and apical proteins in epithelial cells,
      respectively. Confocal microscopy immunofluorescence and electron microscopy
      demonstrated that the apical markers located at the surface toward pulp and
      basolateral markers located at the plasma membrane of odontoblast processes.
      Therefore, odontoblast plasma membrane polarity was different from that in
      epithelial cells. Also, certain lectins stained odontoblast processes while
      others stained the soma, reflecting the different natures of their membrane
      domains. Strong ZO-1 and weaker claudin expression suggest weak tight junctions
      in the odontoblasts. TGF-beta1 showed a tendency to reinstate the expression of
      selected TJ genes, indicating that TGF-beta1 may control odontoblast cell layer
      integrity by controlling tight junction protein expression. 

PMID- 24043712
TI  - Paget's disease of bone: clinical review and update.
AB  - Paget's disease (PD) is a focal disorder of bone remodelling that occurs commonly
      in older people. In this article, we review clinical aspects of PD with an
      emphasis on recent findings. The epidemiology of PD appears to be changing
      rapidly, with several groups in different parts of the world reporting a marked
      reduction in the prevalence and incidence of PD, as well as in the severity of
      disease seen by clinicians. These findings seem most likely to be caused by
      changes in exposure to unknown environmental factors that have a role in the
      development of PD. However, genetic factors are also important. Mutations in
      SQSTM1 occur in 25-50% of familial PD. Genotype-phenotype relationships are
      present, as PD develops at an earlier age and is more extensive and severe in
      those with SQSTM1 mutations, and these findings are more pronounced in those with
      truncating mutations. However, the prevalence of PD in adults with SQSTM1
      mutations is uncertain, and it is not known how such mutations might cause PD.
      Ultimately, if the cause of PD is determined, it seems likely that it will
      include both genetic and environmental factors. Lastly, clinical trials have
      shown that potent bisphosphonates are highly effective treatments for active PD,
      and reduce pain, improve quality of life, normalise bone turnover and heal lytic
      lesions on radiographs. They can also induce sustained remission that persists
      for many years. 

PMID- 24043713
TI  - Human ERV3-1 env protein expression in various human tissues and tumours.

PMID- 24043714
TI  - Decimal numbers and safe interpretation of clinical pathology results.
AB  - OBJECTIVE: To determine the understanding of decimal numbers by medical
      laboratory scientists, doctors and nurses. METHODS: A Decimal Comparison Test
      determined the comprehension of decimals numbers. Additional questions sought the
      participants' understanding of concentrations and reference ranges, and their
      preferences for the presentation of clinical pathology results. RESULTS: Of the
      108 participants, 40% exhibited poor comprehension of decimal numbers. One-third
      of the medical laboratory scientists, a quarter of doctors, and half the nurses
      were characterised as lacking numeracy skills. The majority of participants (60%)
      thought it would be safer for results to be presented as whole numbers rather
      than as decimals with leading zeros. CONCLUSIONS: The number of laboratory and
      clinical staff who show numeracy issues that could lead to misinterpretation of
      clinical pathology results and contribute to medical error strongly supports
      recommendations that pathology results should be presented as whole numbers.

PMID- 24043715
TI  - Evaluation of the HER2 amplification status in oesophageal adenocarcinoma by
      conventional and automated FISH: a tissue microarray study.
AB  - INTRODUCTION: The manual fluorescence in situ hybridisation (FISH) Human
      Epidermal Growth Factor Receptor 2 (HER2)/CEP17 testing method is frequently
      used, however, it is time consuming and liable to subjectivity. Automation of
      FISH might increase the throughput and accuracy. AIM: To evaluate the agreement
      between automated and conventional FISH with regard to a reference test silver
      enhanced in situ hybridization (SISH) for HER2 amplification, as well as its
      prognostic significance. MATERIAL AND METHODS: 154 oesophageal adenocarcinomas
      were included in a tissue microarray. HER2/CEP17 gene amplification was assessed
      by automated FISH and was compared with conventional HER2/CEP17 testing methods.
      RESULTS: 46.8% of patients showed HER2 amplified tumours by automated FISH (ratio
      >=1.8) compared with 18.1% by conventional FISH. A high automated HER2/CEP17
      ratio (>=1.8) was significantly associated with worse survival (HR 1.731; 95% CI
      1.075 to 2.786; p=0.024). However, agreement between automated and conventional
      FISH was only 72.2% and 71.4% between automated FISH and SISH, compared with
      94.6% for conventional FISH/SISH. Therefore, thresholds for HER2/CEP17
      amplification were sequentially raised from HER2/CEP17 ratio 1.8 till 5.0. A
      HER2/CEP17 ratio threshold of >=3.6 had similar prognostic significance as
      conventional FISH (HR 1.880; 95% CI 1.060 to 3.332; p=0.031 vs HR 1.828; 95% CI
      1.102 to 3.033; p=0.020), yielded comparable amplification rates as conventional
      FISH (14.3% vs 18.1%) and comparable agreement to SISH/Immunohistochemistry
      (IHC). CONCLUSIONS: Automation of HER2 FISH analysis in oesophageal cancer has
      not been performed before. Automated HER2 is feasible, but it seems that the
      HER2/CEP17 threshold should be adjusted to >=3.6 to arrive at best comparability
      with other methods and prognostic value.

PMID- 24043716
TI  - Clinical performance evaluation of the CellaVision Image Capture System in the
      white blood cell differential on peripheral blood smears.
AB  - INTRODUCTION: Differential counting and morphological analysis of peripheral
      blood smears is of great diagnostic importance to the clinician. For economic and
      time-saving reasons, automated imaging processes have been successfully
      introduced over the years. The aim of this study was to investigate whether a new
      morphology system, the CellaVision Image Capture System (CICS), can be used to
      perform a white blood cell (WBC) differential on peripheral blood smears.
      METHODS: WBCs in 200 peripheral blood smears were analysed with the CICS method
      and compared with the DM96 method to establish accuracy, short-term imprecision
      and clinical sensitivity and specificity for morphology. For establishing long
      term imprecision, two blood smears were analysed for 20 days with the CICS
      method. RESULTS: Evaluation of accuracy in 199 samples demonstrated a good
      correlation for the CICS when compared with the postclassification on the DM96.
      Regression coefficients ranged from 0.97 for monocyte counts to 0.99 for
      neutrophil counts. All regression lines showed slopes with 1 and intercepts with
      0 within the 95% CI. Long-term imprecision was less than 5% for neutrophils,
      eosinophils, basophils, lymphocytes and monocytes. Comparison of the short-term
      imprecision demonstrated that the SD did not differ by more than 1.1% between the
      DM96 method and the CICS method. Clinical sensitivity of the CICS was 93.5% and
      specificity was 97.8%. Specificity and sensitivity for blasts was 100%.
      CONCLUSIONS: The CICS has proven to be a reliable and accurate tool in the
      differential WBC count on peripheral blood smears and provides small laboratories
      with a 24 h available real-time digital differential WBC count on peripheral
      blood smears and consultation for patients in remote locations.

PMID- 24043717
TI  - A study of alpha5 chain of collagen IV, caldesmon, placental alkaline phosphatase
      and smoothelin as immunohistochemical markers of gastrointestinal smooth muscle
      neoplasms.
AB  - AIMS: The histological distinction between gastrointestinal smooth muscle
      neoplasms (SMNs) and their differential diagnoses, especially gastrointestinal
      stromal tumours (GISTs), has important clinical management implications. This
      study aimed to investigate preliminary data suggesting that loss of the alpha5
      chain of collagen IV (alpha5(IV)), placental acid phosphatase (PLAP) expression
      and smoothelin expression can be used diagnostically as markers of
      gastrointestinal SMNs. To aid this investigation, these potential markers were
      directly compared against caldesmon. METHODS: 31 SMNs and 111 potential
      differential diagnoses (16 different neoplasm types) were immunostained for
      caldesmon, PLAP and smoothelin. RESULTS: A pilot study indicated that loss of
      alpha5(IV) positivity was neither a specific nor sensitive marker of SMN.
      Caldesmon, PLAP and smoothelin were expressed by all 31 SMNs though
      leiomyosarcomas showed some loss of staining proportion and/or intensity.
      Caldesmon positivity was commonly shown by GISTs, glomus tumours and
      angiomyolipomas. Cytoplasmic smoothelin positivity was commonly shown by glomus
      tumours and angiomyolipomas, whereas PLAP positivity was shown by one
      desmoplastic small round cell tumour studied and only infrequently shown by
      angiomyolipomas. Nuclear smoothelin positivity was seen among four
      leiomyosarcomas but also a wide range of non-SMNs. CONCLUSIONS: alpha5(IV)
      immunohistochemistry with the A7 antibody is not a diagnostically useful marker
      of gastrointestinal SMNs. Both PLAP and smoothelin (cytoplasmic expression only)
      are as sensitive as but are more specific than caldesmon as such a marker.
      Further, PLAP and smoothelin immunostainings are technically reliable and can be
      reproducibly assessed.

PMID- 24043718
TI  - Angiomatoid fibrous histiocytoma: clinicopathological and molecular
      characterisation with emphasis on variant histomorphology.
AB  - AIMS: Angiomatoid fibrous histiocytoma (AFH) is histologically typified by
      nodules of histiocytoid spindle cells with pseudoangiomatoid spaces, fibrous
      pseudocapsules and lymphocytic cuffs. The principal goal was to expand the
      spectrum of AFHs through clinicopathological and molecular characterisation.
      METHODS: Thirteen AFHs, including 11 with confirmed hallmark translocation, were
      reappraised for classic features, reactive osteoclasts, mitoses and stromal,
      architectural and cytomorphological variations, with CD99, desmin and EMA stained
      in available cases. RESULTS: Seven male and six female patients ranged in age
      from 4 to 63 years (median, 13), including 4 older than 20 years. Tumours were
      located on the extremities (n=6), trunk (n=4) and scalp (n=3). Although fibrous
      pseudocapsules were observed in all cases, four showed solid histology without
      pseudoangiomatoid spaces and another one lacked peripheral lymphoid infiltrates.
      Nuclear pleomorphism was striking in two cases, moderate in seven and absent in
      four, with osteoclasts seen in two cases. In three AFHs with sclerotic matrix,
      one exhibited perivascular hyalinisation and nuclear palisading, reminiscent of a
      schwannoma. In three varyingly myxoid tumours, one closely resembled a
      myoepithelioma with prominent reticular arrangement of spindle cells in an
      abundant myxoid stroma. Besides EWSR1 gene rearrangement detected in four cases
      by fluorescence in situ hybridisation (FISH), EWSR1-CREB1 fusion was confirmed in
      nine cases, including a schwannoma-like AFH, and EWSR1-ATF1 fusion detected in a
      myoepithelioma-like AFH. Immunohistochemically, 56% of AFHs were positive for
      EMA, 78% for desmin and 100% for CD99. CONCLUSIONS: Molecular testing is
      diagnostic of variant AFHs displaying diverse histomorphological alterations in
      the architectural patterns, cytomorphology and extracellular matrix.

PMID- 24043719
TI  - Failure of efficacy and adverse events associated with dose-intense diminazene
      diaceturate treatment of chronic Cytauxzoon felis infection in five cats.
AB  - Cytauxzoon felis is a hemoprotozoan parasite of cats. While many infected cats
      die of acute illness, some enter a chronic carrier state. To date, no treatment
      has been documented to clear the chronic carrier state, leaving recovered cats to
      act as a potential indirect source of infection via a tick vector. Diminazene
      diaceturate is an anti-protozoal therapy that has been suggested for use in the
      treatment of acute cytauxzoonosis, but which failed to clear the carrier state at
      the dose used in acute illness. We hypothesized that a dose-intensified regimen
      of diminazene could reduce or eliminate parasitemia from five domestic cats
      naturally infected with C felis. Cats were administered 4 mg/kg of diminazene
      diaceturate intramuscularly for 5 consecutive days. Clearance of the organism was
      assessed via semi-quantitative polymerase chain reaction and light microscopy 1,
      3, 6 and 10 weeks after starting treatment. Additionally, cats were monitored for
      adverse drug reactions by daily observation and examination. Complete blood
      count, biochemical profile and urinalysis were performed at 1, 3 and 10 weeks.
      Adverse events were common and included profuse salivation and nausea at the time
      of injection, monoparesis in the injected leg, proteinuria and potential
      hepatotoxicity. Severity of parasitemia was not reduced. Diminazene diaceturate
      cannot be recommended for elimination of the carrier state of C felis infection. 

PMID- 24043720
TI  - Effects of age and reproductive status on postoperative pain after routine
      ovariohysterectomy in cats.
AB  - A prospective clinical trial to compare the effects of age and reproductive
      status on postoperative pain was conducted in 145 female cats undergoing
      ovariohysterectomy using injectable anaesthesia. The cats were grouped
      appropriately: 60 kittens <4 months old (K), 85 adults >4 months old (A) and,
      within the adult group, 57 normal adults (nA) and 28 adults who were either
      pregnant or in oestrus (rA). Pain was assessed using a simple descriptive scale
      (SDS; 0-3), a dynamic and interactive visual scale (DIVAS; 0-100 mm) and
      mechanical nociceptive thresholds (MNT; N, 2 mm diameter probe) pre-operatively
      and at 4 and 24 h postoperatively. Kittens had lower DIVAS areas under the time
      curve and SDS than adults (P <0.05), but similar MNT (K: 3.3 +/- 2.6, A: 4.3 +/-
      2.5 N at 4 h, P >0.05). Data from nA and rA were not different (P >0.05). Kittens
      had similar wound tenderness, but less affective pain than adults, and
      reproductive status had no effect. 

PMID- 24043721
TI  - Trans-iliac pin/bolt/screw internal fixation for sacroiliac luxation or
      separation in cats: six cases.
AB  - Trans-iliac pin, bolt or screw stabilisation was performed on six cats with
      sacroiliac (SI) luxation and separation. For the purpose of this study, SI
      luxation is defined as the separation of the iliac wing from the sacrum without
      fracture of the sacral or iliac wing; SI separation is defined as the separation
      of the iliac wing from the sacrum secondary to fracture of the sacrum and/or the
      iliac wing. Complications, surgical time and medium-to-long-term outcome were
      assessed by a retrospective review of the clinical records and owner
      questionnaires. Postoperative reduction of the SI joint was good-to-excellent in
      all cases and the outcome was considered good-excellent in all cats apart from
      one, where the trans-iliac bolt migrated dorsally from the iliac wing. This cat
      had bilateral SI luxations. Based on our results, trans-iliac fixation of SI
      luxation/separation is associated with good clinical outcome and should be
      considered as a treatment option in unilateral SI luxation in cats. Caution
      should be exercised in the use of trans-iliac pin/bolt as the sole method of
      stabilisation in bilateral SI luxations. 

PMID- 24043722
TI  - Aberrant expression of sLex and sLea as candidate prognostic factors for feline
      mammary gland tumour.
AB  - Expression of the carbohydrate antigens sialyl Lewis x (sLe(x)) and a (sLe(a))
      was evaluated in feline mammary gland tumours (FMGT). Immunohistochemical
      analysis of tissues from 21 FMGT patients and 11 healthy cats revealed
      significantly higher sLe(x) and sLe(a) antigen expression in adenocarcinoma
      tissues compared with that of normal mammary tissues (P <0.01). Serum
      concentration of sLe(x) was evaluated using an enzyme-linked immunosorbent assay
      and was significantly higher in the 11 FMGT patients (4.71 +/- 10.1 U/ml) than
      the 22 patients with other disease (2.69 +/- 1.59 U/ml) (P = 0.03) and the 22
      healthy cats (3.71 +/- 1.10 U/ml), although the latter difference was not
      significant. Although the number of cases examined in this study was small, our
      findings suggest that aberrant expression of sLe antigens may be induced by
      tumourigenesis in FMGT and that sLe antigens are potential prognostic tumour
      markers for FMGT. 

PMID- 24043723
TI  - Burning issues in the meta-analysis of pharmaceutical trials for depression.
AB  - During the last decade a number of meta-analytic studies have been published and
      they triggered a debate on the true clinical usefulness of antidepressants. The
      current article comments on problems within the randomized controlled trials
      design, the study samples, the psychometric scales, the methods of meta-analysis,
      the interpretation of the results, and the reporting of conflicts of interest.
      Although the meta-analyses published so far agree that medication works in severe
      depression, they question its efficacy in mild cases. However, several
      methodological issues should be clarified before conclusions are definite.
      Different methods give different results and similar results seem to entertain a
      variety of interpretations. In the future it is important to address all of these
      problems, and to improve methodology on the basis of clinically informed choices.
      Otherwise, meta-analysis risks alienation from clinical reality and thus risks
      becoming the 21(st) century psychoanalysis. 

PMID- 24043724
TI  - Rapid opiate detoxification and antagonist induction under general anaesthesia or
      intravenous sedation is humane, sometimes essential and should always be an
      option. Three illustrative case reports involving diabetes and epilepsy and a
      review of the literature.
AB  - When abstinence is an appropriate goal, controlled studies and systematic reviews
      confirm that rapid, antagonist-precipitated opiate withdrawal procedures are the
      most effective and cost effective methods of initiating abstinence, and
      naltrexone (NTX) maintenance. While 'rapid' withdrawal, better conceptualised as
      Rapid Antagonist Induction (RAI), can often be humanely achieved with modest
      sedation levels, we present three case histories to support our argument that for
      some patients, general anaesthesia (GA), or techniques of intravenous sedation
      (IVS) that approach GA, are essential for safety and success. This includes
      patients with intercurrent disease (e.g. epilepsy or insulin-dependent diabetes)
      but also those with severe withdrawal phobia after previous distressing
      experiences. We discuss the history of the procedure. The dangers of RAI under GA
      or IVS in experienced hands have been exaggerated and the appropriate expertise
      should be more easily available. Patients and clinicians readily accept risks of
      major surgery for the excessive intake of food that causes most obesity. Similar
      risk-acceptance exists in cosmetic surgery and obstetrics. The increasing use and
      effectiveness of long-acting implants or depot-injections of NTX for relapse
      prevention have largely solved compliance problems that undermined the potential
      of oral NTX. Their ability to prevent opiate overdose in abstinent, non-tolerant
      patients also strengthens arguments both for offering RAI as a therapeutic option
      and for reducing psychological, professional and practical barriers to using it. 

PMID- 24043725
TI  - Attenuation of acute d-amphetamine-induced disruption of conflict resolution by
      clozapine, but not alpha-flupenthixol in rats.
AB  - Previous research demonstrates that disruption of forebrain dopamine systems
      impairs the use of high-order information to guide goal-directed performance, and
      that this deficit may be related to impaired use of task-setting cues in patients
      with schizophrenia. Such deficits can be interrogated through conflict
      resolution, which has been demonstrated to be sensitive to prefrontal integrity
      in rodents. We sought to examine the effects of acute systemic d-amphetamine
      administration on the contextual control of response conflict in rats, and
      whether deficits were reversed through pre-treatment with clozapine or the D1/D2
      antagonist alpha-flupenthixol. Acute d-amphetamine (1.5 mg/kg) disrupted the
      utilisation of contextual cues; therefore rats were impaired during presentation
      of stimulus compounds that require conflict resolution. Evidence suggested that
      this effect was attenuated through pre-treatment with the atypical antipsychotic
      clozapine (5.0 mg/kg), but not the typical antipsychotic alpha-flupenthixol (0.25
      mg/kg), at doses previously shown to attenuate d-amphetamine-induced cognitive
      deficits. These studies therefore demonstrate a potentially viable model of
      disrupted executive function such as that seen in schizophrenia.

PMID- 24043726
TI  - Revised staging classification improves outcome prediction for small intestinal
      neuroendocrine tumors.
AB  - PURPOSE: Small intestinal (SI) neuroendocrine tumors (NETs) have heterogeneous
      outcomes. The NET societies have recently proposed a TNM staging classification.
      In this study, we used population-based data to assess the validity of the
      staging system. PATIENTS AND METHODS: We identified patients with SI-NETS
      diagnosed between 1988 and 2009 from the Surveillance, Epidemiology, and End
      Results registry. We used Kaplan-Meier analysis to assess disease-specific
      survival according to TNM status. Cox models were constructed to evaluate
      differences in prognosis after controlling for potential confounders. RESULTS: We
      identified 6,792 patients with SI-NET. Although the current staging system was
      predictive of prognosis, there was overlap among some groups (stage I/IIA, P =
      .36; stage IIB/IIIB, P = .70). Additionally, stage IIIB patients had better
      survival than stage IIIA patients (P < .001). Adjusted analyses showed similar
      outcomes for T1 versus T2 disease (hazard ratio [HR], 1.02; 95% CI, 0.63 to
      1.66). Patients with T3 (HR, 3.60; 95% CI, 2.28 to 5.69) and T4 (HR, 5.50; 95%
      CI, 3.42 to 8.86) tumors had significantly worse survival than patients with T1
      disease. N1 involvement conferred worse survival in T1 (HR, 3.08; 95% CI, 1.75 to
      5.44) and T2 disease (HR, 2.73; 95% CI, 1.84 to 4.07) but not in T3 (HR, 0.99;
      95% CI, 0.76 to 1.30) or T4 (HR, 0.98; 95% CI, 0.71 to 1.35) disease. A revised
      classification showed no overlap in survival across groups. CONCLUSION:
      Progressively more advanced T status is associated with worse SI-NET prognosis.
      Regional lymph node involvement is a marker of worse survival only among patients
      with T1 or T2 status. These results suggest that revisions to the current staging
      classification may be helpful.

PMID- 24043727
TI  - Cost of the cure.

PMID- 24043728
TI  - Wither the cooperative groups?

PMID- 24043729
TI  - Histomolecular phenotypes of adenocarcinoma of the ampulla of vater: more
      evidence is required.

PMID- 24043730
TI  - Reply to G.F. Arroyo.

PMID- 24043731
TI  - Economic burden of cancer survivorship among adults in the United States.
AB  - PURPOSE: To present nationally representative estimates of the impact of cancer
      survivorship on medical expenditures and lost productivity among adults in the
      United States. METHODS: Using the 2008 to 2010 Medical Expenditure Panel Survey,
      we identified 4,960 cancer survivors and 64,431 individuals without a history of
      cancer age >= 18 years. Direct medical costs were measured using annual health
      care expenditures and examined by source of payment and service type. Indirect
      morbidity costs were estimated from lost productivity as a result of employment
      disability, missed work days, and lost household productivity. We evaluated the
      economic burden of cancer survivorship by estimating excess costs among cancer
      survivors, stratified by time since diagnosis (recently diagnosed [<= 1 year] and
      previously diagnosed [> 1 year]), compared with individuals without a history of
      cancer using multivariable regression models stratified by age (18 to 64 and >=
      65 years), controlling for age, sex, race/ethnicity, education, and
      comorbidities. RESULTS: In 2008 to 2010, the annual excess economic burden of
      cancer survivorship among recently diagnosed cancer survivors was $16,213 per
      survivor age 18 to 64 years and $16,441 per survivor age >= 65 years. Among
      previously diagnosed cancer survivors, the annual excess burden was $4,427 per
      survivor age 18 to 64 years and $4,519 per survivor age >= 65 years. Excess
      medical expenditures composed the largest share of the economic burden among
      cancer survivors, particularly among those recently diagnosed. CONCLUSION: The
      economic impact of cancer survivorship is considerable and is also high years
      after a cancer diagnosis. Efforts to reduce the economic burden caused by cancer
      will be increasingly important given the growing population of cancer survivors.

PMID- 24043732
TI  - Use of early tumor shrinkage to predict long-term outcome in metastatic
      colorectal cancer treated with cetuximab.
AB  - PURPOSE: Early tumor shrinkage (ETS) is associated with long-term outcome in
      patients with chemorefractory metastatic colorectal cancer (mCRC) receiving
      cetuximab. This association was investigated in the first-line setting in the
      randomized CRYSTAL and OPUS mCRC trials, after controlling for KRAS tumor
      mutation status. METHODS: Radiologic assessments at week 8 were used to calculate
      the relative change in the sum of the longest diameters of the target lesions.
      Time-dependent receiver operating characteristics provided Ctau-indices (time
      dependent c-index). Cox regression models and subpopulation treatment effect
      pattern plot analysis investigated associations between ETS (radiologic tumor
      size decrease at week 8) and survival and progression-free survival (PFS).
      RESULTS: In both trials, in patients with KRAS wild-type mCRC, Ctau values for
      PFS and survival were higher (P < .001) in those receiving chemotherapy plus
      cetuximab versus chemotherapy alone, indicating a stronger predictive value of
      ETS for long-term outcome in these patients. In the CRYSTAL and OPUS trials,
      respectively, the cutoff value of ETS >= 20% (v < 20%) identified patients with
      KRAS wild-type mCRC receiving chemotherapy plus cetuximab with longer PFS
      (medians 14.1 v 7.3 months, hazard ratio [HR] = 0.32; P < .001, and medians 11.9
      v 5.7 months, HR = 0.22; P < .001) and survival (medians 30.0 v 18.6 months, HR =
      0.53; P < .001 and medians 26.0 v 15.7 months, HR = 0.43; P = .006). CONCLUSION:
      ETS was significantly associated with long-term outcome in patients with KRAS
      wild-type mCRC treated first-line with chemotherapy plus cetuximab. Validation in
      prospective trials is required to assess the value of this on-treatment marker in
      the clinical decision-making process.

PMID- 24043733
TI  - Randomized trial of decongestive lymphatic therapy for the treatment of
      lymphedema in women with breast cancer.
AB  - PURPOSE: Because of its morbidity and chronicity, arm lymphedema remains a
      concerning complication of breast cancer treatment. Although massage-based
      decongestive therapy is often recommended, randomized trials have not
      consistently demonstrated benefit over more conservative measures. PATIENTS AND
      METHODS: Women previously treated for breast cancer with lymphedema were enrolled
      from six institutions. Volumes were calculated from circumference measurements.
      Patients with a minimum of 10% volume difference between their arms were randomly
      assigned to either compression garments (control) or daily manual lymphatic
      drainage and bandaging followed by compression garments (experimental). The
      primary outcome was percent reduction in excess arm volume from baseline to 6
      weeks. RESULTS: A total of 103 women were randomly assigned, and 95 were
      evaluable. Mean reduction of excess arm volume was 29.0% in the experimental
      group and 22.6% in the control group (difference, 6.4%; 95% CI, -6.8% to 20.5%; P
      = .34). Absolute volume loss was 250 mL and 143 mL in the experimental and
      control groups, respectively (difference, 107 mL; 95% CI, 13 to 203 mL; P = .03).
      There was no difference between groups in the proportion of patients losing 50%
      or greater excess arm volume. Quality of life (Short Form-36 Health Survey) and
      arm function were not different between groups. CONCLUSION: This trial was unable
      to demonstrate a significant improvement in lymphedema with decongestive therapy
      compared with a more conservative approach. The failure to detect a difference
      may have been a result of the relatively small size of our trial.

PMID- 24043734
TI  - Building bridges to conquer cancer.

PMID- 24043735
TI  - Targeting the RANKL pathway: putting the brakes on prostate cancer progression in
      bone.

PMID- 24043736
TI  - Lymphoma occurring during pregnancy: antenatal therapy, complications, and
      maternal survival in a multicenter analysis.
AB  - PURPOSE: Lymphoma is the fourth most frequent cancer in pregnancy; however,
      current clinical practice is based largely on small series and case reports.
      PATIENTS AND METHODS: In a multicenter retrospective analysis, we examined
      treatment, complications, and outcomes for Hodgkin lymphoma (HL) and non-Hodgkin
      lymphoma (NHL) occurring during pregnancy. RESULTS: Among 90 patients (NHL, n =
      50; HL, n = 40), median age was 30 years (range, 18 to 44 years) and median
      diagnosis occurred at 24 weeks gestation. Of patients with NHL, 52% had advanced
      stage versus 25% of patients with HL (P = .01). Pregnancy was terminated in six
      patients. Among the other 84 patients, 28 (33%) had therapy deferred to
      postpartum; these patients were diagnosed at a median 30 weeks gestation. This
      compared with 56 patients (67%) who received antenatal therapy with median
      lymphoma diagnosis at 21 weeks (P < .001); 89% of these patients received
      combination chemotherapy. The most common preterm complication was induction of
      labor (33%). Gestation went to full term in 56% of patients with delivery
      occurring at a median of 37 weeks. There were no differences in maternal
      complications, perinatal events, or median infant birth weight based on deferred
      versus antenatal therapy. At 41 months, 3-year progression-free survival (PFS)
      and overall survival (OS) for NHL were 53% and 82%, respectively, and 85% and
      97%, respectively, for HL. On univariate analysis for NHL, radiotherapy predicted
      inferior PFS, and increased lactate dehydrogenase and poor Eastern Cooperative
      Oncology Group performance status (ECOG PS) portended worse OS. For HL patients,
      nulliparous status and "B" symptoms predicted inferior PFS. CONCLUSION: Standard
      (non-antimetabolite) combination chemotherapy administered past the first
      trimester, as early as 13 weeks gestation, was associated with few complications
      and expected maternal survival with lymphoma occurring during pregnancy.

PMID- 24043738
TI  - Allelic polymorphisms of inhibitory killer immunoglobulin-like receptor natural
      killer cell function can also influence the graft-versus-leukemia response.

PMID- 24043737
TI  - Solid tumors after chemotherapy or surgery for testicular nonseminoma: a
      population-based study.
AB  - PURPOSE: Increased risks of solid tumors after older radiotherapy strategies for
      testicular cancer (TC) are well established. Few population-based studies,
      however, focus on solid cancer risk among survivors of TC managed with
      nonradiotherapy approaches. We quantified the site-specific risk of solid cancers
      among testicular nonseminoma patients treated in the modern era of cisplatin
      based chemotherapy, without radiotherapy. PATIENTS AND METHODS: Standardized
      incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with
      testicular nonseminoma reported to the population-based Surveillance,
      Epidemiology, and End Results program (1980 to 2008) and treated initially with
      either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy.
      Patients accrued 116,073 person-years of follow-up. RESULTS: Two hundred ten
      second solid cancers were observed. No increased risk followed surgery alone
      (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly
      increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers)
      occurred after chemotherapy. Increased risks of solid cancers after chemotherapy
      were observed in most follow-up periods (median latency, 12.5 years), including
      more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33);
      significantly increased three- to seven-fold risks occurred for cancers of the
      kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to
      7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78). CONCLUSION: To our
      knowledge, this is the first large population-based series reporting
      significantly increased risks of solid cancers among patients with testicular
      nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent
      analytic studies should focus on the evaluation of dose-response relationships,
      types of solid cancers, latency patterns, and interactions with other possible
      factors, including genetic susceptibility.

PMID- 24043739
TI  - Breast-conserving treatment with or without radiotherapy in ductal carcinoma In
      Situ: 15-year recurrence rates and outcome after a recurrence, from the EORTC
      10853 randomized phase III trial.
AB  - PURPOSE: Adjuvant radiotherapy (RT) after a local excision (LE) for ductal
      carcinoma in situ (DCIS) aims at reduction of the incidence of a local recurrence
      (LR). We analyzed the long-term risk on developing LR and its impact on survival
      after local treatment for DCIS. PATIENTS AND METHODS: Between 1986 and 1996,
      1,010 women with complete LE of DCIS less than 5 cm were randomly assigned to no
      further treatment (LE group, n = 503) or RT (LE+RT group, n = 507). The median
      follow-up time was 15.8 years. RESULTS: Radiotherapy reduced the risk of any LR
      by 48% (hazard ratio [HR], 0.52; 95% CI, 0.40 to 0.68; P < .001). The 15-year LR
      free rate was 69% in the LE group, which was increased to 82% in the LE+RT group.
      The 15-year invasive LR-free rate was 84% in the LE group and 90% in the LE+RT
      group (HR, 0.61; 95% CI, 0.42 to 0.87). The differences in LR in both arms did
      not lead to differences in breast cancer-specific survival (BCSS; HR, 1.07; 95%
      CI, 0.60 to 1.91) or overall survival (OS; HR, 1.02; 95% CI, 0.71 to 1.44).
      Patients with invasive LR had a significantly worse BCSS (HR, 17.66; 95% CI, 8.86
      to 35.18) and OS (HR, 5.17; 95% CI, 3.09 to 8.66) compared with those who did not
      experience recurrence. A lower overall salvage mastectomy rate after LR was
      observed in the LE+RT group than in the LE group (13% v 19%, respectively).
      CONCLUSION: At 15 years, almost one in three nonirradiated women developed an LR
      after LE for DCIS. RT reduced this risk by a factor of 2. Although women who
      developed an invasive recurrence had worse survival, the long-term prognosis was
      good and independent of the given treatment.

PMID- 24043740
TI  - Prediction of survival by [18F]fluorodeoxyglucose positron emission tomography in
      patients with locally advanced non-small-cell lung cancer undergoing definitive
      chemoradiation therapy: results of the ACRIN 6668/RTOG 0235 trial.
AB  - PURPOSE: In this prospective National Cancer Institute-funded American College of
      Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group
      trial, we hypothesized that standardized uptake value (SUV) on post-treatment
      [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with
      survival in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS:
      Patients received conventional concurrent platinum-based chemoradiotherapy
      without surgery; postradiotherapy consolidation chemotherapy was allowed. Post
      treatment FDG-PET was performed at approximately 14 weeks after radiotherapy.
      SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both
      institutional and central review readings), with institutional SUVpeak as the
      primary end point. Relationships between the continuous and categorical (cutoff)
      SUVs and survival were analyzed using Cox proportional hazards multivariate
      models. RESULTS: Of 250 enrolled patients (226 were evaluable for pretreatment
      SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year
      survival rate for the entire population was 42.5%. Pretreatment SUVpeak and
      SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival.
      Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post
      treatment SUVpeak was associated with survival in a continuous variable model
      (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a
      prespecified binary value (<= v > 3.5), there was no association with survival.
      However, in exploratory analyses, significant results for survival were found
      using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were
      similar when SUVmax was used in univariate and multivariate models in place of
      SUVpeak. CONCLUSION: Higher post-treatment tumor SUV (SUVpeak or SUVmax) is
      associated with worse survival in stage III NSCLC, although a clear cutoff value
      for routine clinical use as a prognostic factor is uncertain at this time.

PMID- 24043741
TI  - Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed
      and refractory aggressive B- and T-cell non-Hodgkin lymphomas.
AB  - PURPOSE: Aurora A kinase (AAK) is overexpressed in aggressive lymphomas and can
      correlate with more histologically aggressive forms of disease. We therefore
      designed a phase II study of alisertib, a selective AAK inhibitor, in patients
      with relapsed and refractory aggressive non-Hodgkin lymphomas. PATIENTS AND
      METHODS: Patients age >= 18 years were eligible if they had relapsed or
      refractory diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL),
      transformed follicular lymphoma, Burkitt's lymphoma, or noncutaneous T-cell
      lymphoma. Alisertib was administered orally at 50 mg twice daily for 7 days in 21
      day cycles. RESULTS: We enrolled 48 patients. Histologies included DLBCL (n =
      21), MCL (n = 13), peripheral T-cell lymphoma (n = 8), transformed follicular
      lymphoma (n = 5), and Burkitt's (n = 1). Most common grade 3 to 4 adverse events
      were neutropenia (63%), leukopenia (54%), anemia (35%), thrombocytopenia (33%),
      stomatitis (15%), febrile neutropenia (13%), and fatigue (6%). Four deaths during
      the study were attributed to progressive non-Hodgkin lymphoma (n = 2), treatment
      related sepsis (n = 1), and unknown cause (n = 1). The overall response rate was
      27%, including responses in three of 21 patients with DLBCL, three of 13 with
      MCL, one of one with Burkitt's lymphoma, two of five with transformed follicular
      lymphoma, and four of eight with noncutaneous T-cell lymphoma. The alisertib
      steady-state trough concentration (n = 25) revealed the expected pharmacokinetic
      variability, with a trend for higher incidence of adverse event-related dose
      reductions at higher trough concentrations. Analysis for AAK gene amplification
      and total AAK protein revealed no differences between histologies or correlation
      with clinical response. CONCLUSION: The novel AAK inhibitor alisertib seems
      clinically active in both B- and T-cell aggressive lymphomas. On the basis of
      these results, confirmatory single-agent and combination studies have been
      initiated.

PMID- 24043742
TI  - Randomized controlled trial of intensity-modulated radiotherapy for early breast
      cancer: 5-year results confirm superior overall cosmesis.
AB  - PURPOSE: There are few randomized controlled trial data to confirm that improved
      homogeneity with simple intensity-modulated radiotherapy (IMRT) decreases late
      breast tissue toxicity. The Cambridge Breast IMRT trial investigated this
      hypothesis, and the 5-year results are reported. PATIENTS AND METHODS: Standard
      tangential plans of 1,145 trial patients were analyzed; 815 patients had
      inhomogeneous plans (>= 2 cm(3) receiving 107% of prescribed dose: 40 Gy in 15
      fractions over 3 weeks) and were randomly assigned to standard radiotherapy (RT)
      or replanned with simple IMRT; 330 patients with satisfactory dose homogeneity
      were treated with standard RT and underwent the same follow-up as the randomly
      assigned patients. Breast tissue toxicities were assessed at 5 years using
      validated methods: photographic assessment (overall cosmesis and breast shrinkage
      compared with baseline pre-RT photographs) and clinical assessment
      (telangiectasia, induration, edema, and pigmentation). Comparisons between
      different groups were analyzed using polychotomous logistic regression. RESULTS:
      On univariate analysis, compared with standard RT, fewer patients in the simple
      IMRT group developed suboptimal overall cosmesis (odds ratio [OR], 0.68; 95% CI,
      0.48 to 0.96; P = .027) and skin telangiectasia (OR, 0.58; 95% CI, 0.36 to 0.92;
      P = .021). No evidence of difference was seen for breast shrinkage, breast edema,
      tumor bed induration, or pigmentation. The benefit of IMRT was maintained on
      multivariate analysis for both overall cosmesis (P = .038) and skin
      telangiectasia (P = .031). CONCLUSION: Improved dose homogeneity with simple IMRT
      translates into superior overall cosmesis and reduces the risk of skin
      telangiectasia. These results are practice changing and should encourage centers
      still using two-dimensional RT to implement simple breast IMRT.

PMID- 24043744
TI  - Mounting evidence against complex decongestive therapy as a first-line treatment
      for early lymphedema.

PMID- 24043743
TI  - Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an
      ipilimumab-responsive melanoma.

PMID- 24043745
TI  - Everolimus for previously treated advanced gastric cancer: results of the
      randomized, double-blind, phase III GRANITE-1 study.
AB  - PURPOSE: The oral mammalian target of rapamycin inhibitor everolimus demonstrated
      promising efficacy in a phase II study of pretreated advanced gastric cancer.
      This international, double-blind, phase III study compared everolimus efficacy
      and safety with that of best supportive care (BSC) in previously treated advanced
      gastric cancer. PATIENTS AND METHODS: Patients with advanced gastric cancer that
      progressed after one or two lines of systemic chemotherapy were randomly assigned
      to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given
      with BSC. Randomization was stratified by previous chemotherapy lines (one v two)
      and region (Asia v rest of the world [ROW]). Treatment continued until disease
      progression or intolerable toxicity. Primary end point was overall survival (OS).
      Secondary end points included progression-free survival (PFS), overall response
      rate, and safety. RESULTS: Six hundred fifty-six patients (median age, 62.0
      years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and
      4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124).
      Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms,
      respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse
      events included anemia, decreased appetite, and fatigue. The safety profile was
      similar in patients enrolled in Asia versus ROW. CONCLUSION: Compared with BSC,
      everolimus did not significantly improve overall survival for advanced gastric
      cancer that progressed after one or two lines of previous systemic chemotherapy.
      The safety profile observed for everolimus was consistent with that observed for
      everolimus in other cancers.

PMID- 24043746
TI  - Barriers against psychosocial communication: oncologists' perceptions.
AB  - PURPOSE: To explore oncologists' psychosocial attitudes and beliefs and their
      perceptions regarding barriers against psychosocial communication. METHODS: A
      questionnaire was distributed to oncologists in Sweden (n = 537). Questions
      covered demography, the Physician Psychosocial Beliefs Scale (PPBS), and barriers
      against psychosocial communication. Stepwise multiple regression was used to
      determine what factors contribute the most to the PPBS score and the total number
      of barriers and barriers affecting clinical practice, respectively. Spearman rank
      order correlation was used to determine correlation between PPBS score and number
      of barriers. RESULTS: Questionnaire response rate was 64%. Mean PPBS value was
      85.5 (range, 49 to 123; SD, 13.0). Most oncologists (93%) perceived one or more
      barriers in communicating psychosocial aspects with patients. On average, five
      different communication barriers were perceived, of which most were perceived to
      affect clinical practice. These barriers included insufficient consultation time,
      lack of resources for taking care of problems discovered, and lack of methods to
      evaluate patients' psychosocial health in clinical practice. There was a positive
      correlation (rs = 0.490; P < .001) between the PPBS score and the number of
      perceived barriers (ie, less psychosocially oriented oncologists perceived more
      barriers). Oncologists with supplementary education with a psychosocial focus
      perceived fewer barriers/barriers affecting clinical practice (P < .001 and P =
      .001, respectively) and were more psychosocially oriented (P = .001). CONCLUSION:
      Oncologists perceive many different barriers affecting psychosocial communication
      in clinical practice. Interventions aiming to improve psychosocial communication
      must therefore be multifaceted and individualized to clinics and individual
      oncologists. It is important to minimize barriers to facilitate optimal care and
      treatment of patients with cancer.

PMID- 24043747
TI  - Melanoma epidemic: an analysis of six decades of data from the Connecticut Tumor
      Registry.
AB  - PURPOSE: Melanoma is the most commonly fatal form of skin cancer, with nearly
      50,000 annual deaths worldwide. We sought to assess long-term trends in the
      incidence and mortality of melanoma in a state with complete and consistent
      registration. METHODS: We used data from the Connecticut Tumor Registry, the
      original National Cancer Institute SEER site, to determine trends in invasive
      melanoma (1950-2007), in situ melanoma (1973-2007), tumor thickness (1993-2007),
      mortality (1950-2007), and mortality to incidence (1950-2007) among the 19,973
      and 3,635 Connecticut residents diagnosed with invasive melanoma (1950-2007) and
      who died as a result of melanoma (1950-2007), respectively. Main outcome measures
      included trends in incidence and mortality by age, sex, and birth cohort.
      RESULTS: In the initial period (1950-1954), a diagnosis of invasive melanoma was
      rare, with 1.9 patient cases per 100,000 for men and 2.6 patient cases per
      100,000 for women. Between 1950 and 2007, overall incidence rates rose more than
      17-fold in men (1.9 to 33.5 per 100,000) and more than nine-fold in women (2.6 to
      25.3 per 100,000). During these six decades, mortality rates more than tripled in
      men (1.6 to 4.9 per 100,000) and doubled in women (1.3 to 2.6 per 100,000).
      Mortality rates were generally stable or decreasing in men and women through age
      54 years. CONCLUSION: Unremitting increases in incidence and mortality of
      melanoma call for a nationally coordinated effort to encourage and promote
      innovative prevention and early-detection efforts.

PMID- 24043748
TI  - Aurora kinase inhibition as an anticancer strategy.

PMID- 24043749
TI  - Effect of donor KIR2DL1 allelic polymorphism on the outcome of pediatric
      allogeneic hematopoietic stem-cell transplantation.
AB  - PURPOSE: Killer-cell immunoglobulin-like receptors (KIRs) that regulate natural
      killer cells are highly polymorphic. Some KIR2DL1 alleles encode receptors that
      have stronger signaling function than others. We tested the hypothesis that the
      clinical outcomes of allogeneic hematopoietic stem-cell transplantation (HSCT)
      could be affected by donor KIR2DL1 polymorphism. PATIENTS AND METHODS: All 313
      pediatric patients received allogeneic HSCT at a single institution. Donor
      KIR2DL1 functional allele typing was retrospectively performed using single
      nucleotide polymorphism assay. RESULTS: Patients who received a donor graft
      containing the functionally stronger KIR2DL1 allele with arginine at amino acid
      position 245 (KIR2DL1-R(245)) had better survival (P = .0004) and lower
      cumulative incidence of disease progression (P = .001) than those patients who
      received a donor graft that contained only the functionally weaker KIR2DL1 allele
      with cysteine at the same position (KIR2DL1-C(245)). The effect of KIR2DL1
      allelic polymorphism was similar in patients with acute myeloid leukemia or acute
      lymphoblastic leukemia among all allele groups (P >= .71). Patients who received
      a KIR2DL1-R(245)-positive graft with HLA-C receptor-ligand mismatch had the best
      survival (P = .00003) and lowest risk of leukemia progression (P = .0005)
      compared with those who received a KIR2DL1-C(245) homozygous graft. CONCLUSION:
      Donor KIR2DL1 allelic polymorphism affects recipient outcomes after allogeneic
      HSCT. These findings have substantial implications for prognostication and donor
      selection.

PMID- 24043750
TI  - Response phenotype as a predictive biomarker to guide treatment with targeted
      therapies.

PMID- 24043752
TI  - Death and seniors' health dominate CMA annual meeting.

PMID- 24043751
TI  - Denosumab and bone metastasis-free survival in men with nonmetastatic castration
      resistant prostate cancer: exploratory analyses by baseline prostate-specific
      antigen doubling time.
AB  - PURPOSE: Denosumab, an anti-RANK ligand monoclonal antibody, significantly
      increases bone metastasis-free survival (BMFS; hazard ratio [HR], 0.85; P = .028)
      and delays time to first bone metastasis in men with nonmetastatic castration
      resistant prostate cancer (CRPC) and baseline prostate-specific antigen (PSA) >=
      8.0 ng/mL and/or PSA doubling time (PSADT) <= 10.0 months. To identify men at
      greatest risk for bone metastasis or death, we evaluated relationships between
      PSA and PSADT with BMFS in the placebo group and the efficacy and safety of
      denosumab in men with PSADT <= 10, <= 6, and <= 4 months. PATIENTS AND METHODS: A
      total of 1,432 men with nonmetastatic CRPC were randomly assigned 1:1 to monthly
      subcutaneous denosumab 120 mg or placebo. Enrollment began February 2006; primary
      analysis cutoff was July 2010, when approximately 660 men were anticipated to
      have developed bone metastases or died. RESULTS: In the placebo group, shorter
      BMFS was observed as PSADT decreased below 8 months. In analyses by shorter
      baseline PSADT, denosumab consistently increased BMFS by a median of 6.0, 7.2,
      and 7.5 months among men with PSADT <= 10 (HR, 0.84; P = .042), <= 6 (HR, 0.77; P
      = .006), and <= 4 months (HR, 0.71; P = .004), respectively. Denosumab also
      consistently increased time to bone metastasis by PSADT subset. No difference in
      survival was observed between treatment groups for the overall study population
      or PSADT subsets. CONCLUSION: Patients with shorter PSADT are at greater risk for
      bone metastasis or death. Denosumab consistently improves BMFS in men with
      shorter PSADT and seems to have the greatest treatment effects in men at high
      risk for progression.

PMID- 24043753
TI  - Big alcohol catches up with all adolescents.

PMID- 24043754
TI  - Concerns with fibromyalgia guidelines.

PMID- 24043755
TI  - Concerns with fibromyalgia guidelines.

PMID- 24043756
TI  - In vivo adeno-associated viral vector-mediated genetic engineering of white and
      brown adipose tissue in adult mice.
AB  - Adipose tissue is pivotal in the regulation of energy homeostasis through the
      balance of energy storage and expenditure and as an endocrine organ. An
      inadequate mass and/or alterations in the metabolic and endocrine functions of
      adipose tissue underlie the development of obesity, insulin resistance, and type
      2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved
      in adipose dysfunction, in vivo genetic modification of adipocytes holds great
      potential. Here, we demonstrate that adeno-associated viral (AAV) vectors,
      especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and
      brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of
      short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or
      micro-RNA target sequences enabled highly specific, long-term AAV-mediated
      transgene expression in white or brown adipocytes. As proof of concept, delivery
      of AAV vectors encoding for hexokinase or vascular endothelial growth factor to
      WAT or BAT resulted in increased glucose uptake or increased vessel density in
      targeted depots. This method of gene transfer also enabled the secretion of
      stable high levels of the alkaline phosphatase marker protein into the
      bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of
      adipose tissue represents a useful tool for the study of adipose pathophysiology
      and, likely, for the future development of new therapeutic strategies for obesity
      and diabetes. 

PMID- 24043757
TI  - Adipose mesenchymal stromal cells isolated from type 2 diabetic patients display
      reduced fibrinolytic activity.
AB  - Stem cells have been successfully used for the treatment of critical limb
      ischemia (CLI). We conducted a clinical trial to determine the feasibility of
      using autologous adipose-derived mesenchymal stromal cells (AdMSCs) for the
      treatment of CLI. Unexpectedly, two diabetic patients developed peripheral
      microthrombosis. This adverse effect, which contrasts with the reported
      antithrombotic properties of MSCs, may stem from the diabetic environment that
      alters the fibrinolytic activity of AdMSCs, thereby increasing the probability of
      developing thrombosis. Here, we confirm this premise by demonstrating that
      diabetic AdMSCs cultured in the presence of blood sera expressed and released
      higher levels of plasminogen activator inhibitor type 1, reduced levels of tissue
      plasminogen activator, and lower d-dimer formation compared with nondiabetic
      AdMSCs. Thus, to establish an appropriate cell therapy for diabetic patients, we
      recommend including new preclinical safety tests, such as the d-dimer and/or the
      tissue plasminogen activator-to-plasminogen activator inhibitor type 1 ratio
      tests, to assess fibrinolytic activity of cells before implantation. 

PMID- 24043758
TI  - p53-dependent chemokine production by senescent tumor cells supports NKG2D
      dependent tumor elimination by natural killer cells.
AB  - The induction of cellular senescence is an important mechanism by which p53
      suppresses tumorigenesis. Using a mouse model of liver carcinoma, where cellular
      senescence is triggered in vivo by inducible p53 expression, we demonstrated that
      NK cells participate in the elimination of senescent tumors. The elimination of
      senescent tumor cells is dependent on NKG2D. Interestingly, p53 restoration
      neither increases ligand expression nor increases the sensitivity to lysis by NK
      cells. Instead, p53 restoration caused tumor cells to secrete various chemokines
      with the potential to recruit NK cells. Antibody-mediated neutralization of CCL2,
      but not CCL3, CCL4 or CCL5, prevented NK cell recruitment to the senescent tumors
      and reduced their elimination. Our findings suggest that elimination of senescent
      tumors by NK cells occurs as a result of the cooperation of signals associated
      with p53 expression or senescence, which regulate NK cell recruitment, and other
      signals that induce NKG2D ligand expression on tumor cells. 

PMID- 24043759
TI  - Phosphofructokinase deficiency impairs ATP generation, autophagy, and redox
      balance in rheumatoid arthritis T cells.
AB  - In the HLA class II-associated autoimmune syndrome rheumatoid arthritis (RA), CD4
      T cells are critical drivers of pathogenic immunity. We have explored the
      metabolic activity of RA T cells and its impact on cellular function and fate.
      Naive CD4 T cells from RA patients failed to metabolize equal amounts of glucose
      as age-matched control cells, generated less intracellular ATP, and were
      apoptosis-susceptible. The defect was attributed to insufficient induction of 6
      phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a regulatory and
      rate-limiting glycolytic enzyme known to cause the Warburg effect. Forced
      overexpression of PFKFB3 in RA T cells restored glycolytic flux and protected
      cells from excessive apoptosis. Hypoglycolytic RA T cells diverted glucose toward
      the pentose phosphate pathway, generated more NADPH, and consumed intracellular
      reactive oxygen species (ROS). PFKFB3 deficiency also constrained the ability of
      RA T cells to resort to autophagy as an alternative means to provide energy and
      biosynthetic precursor molecules. PFKFB3 silencing and overexpression identified
      a novel extraglycolytic role of the enzyme in autophagy regulation. In essence, T
      cells in RA patients, even those in a naive state, are metabolically reprogrammed
      with insufficient up-regulation of the glycolytic activator PFKFB3, rendering
      them energy-deprived, ROS- and autophagy-deficient, apoptosis-sensitive, and
      prone to undergo senescence. 

PMID- 24043760
TI  - Inhibition of the p110alpha isoform of PI 3-kinase stimulates nonfunctional tumor
      angiogenesis.
AB  - Understanding the direct, tumor cell-intrinsic effects of PI 3-kinase (PI3K) has
      been a key focus of research to date. Here, we report that cancer cell-extrinsic
      PI3K activity, mediated by the p110alpha isoform of PI3K, contributes in an
      unexpected way to tumor angiogenesis. In syngeneic mouse models, inactivation of
      stromal p110alpha led to increased vascular density, reduced vessel size, and
      altered pericyte coverage. This increased vascularity lacked functionality,
      correlating with enhanced tumor hypoxia and necrosis, and reduced tumor growth.
      The role of p110alpha in tumor angiogenesis is multifactorial, and includes
      regulation of proliferation and DLL4 expression in endothelial cells. p110alpha
      in the tumor stroma is thus a regulator of vessel formation, with p110alpha
      inactivation giving rise to nonfunctional angiogenesis, which can stunt tumor
      growth. This type of vascular aberration differs from vascular endothelial growth
      factor-centered antiangiogenesis therapies, which mainly lead to vascular
      pruning. Inhibition of p110alpha may thus offer a new antiangiogenic therapeutic
      opportunity in cancer. 

PMID- 24043761
TI  - A Toxoplasma dense granule protein, GRA24, modulates the early immune response to
      infection by promoting a direct and sustained host p38 MAPK activation.
AB  - Toxoplasma gondii, the causative agent of toxoplasmosis, is an obligate
      intracellular protozoan parasite that resides inside a parasitophorous vacuole.
      During infection, Toxoplasma actively remodels the transcriptome of its hosting
      cells with profound and coupled impact on the host immune response. We report
      that Toxoplasma secretes GRA24, a novel dense granule protein which traffics from
      the vacuole to the host cell nucleus. Once released into the host cell, GRA24 has
      the unique ability to trigger prolonged autophosphorylation and nuclear
      translocation of the host cell p38alpha MAP kinase. This noncanonical kinetics of
      p38alpha activation correlates with the up-regulation of the transcription
      factors Egr-1 and c-Fos and the correlated synthesis of key proinflammatory
      cytokines, including interleukin-12 and the chemokine MCP-1, both known to
      control early parasite replication in vivo. Remarkably, the GRA24-p38alpha
      complex is defined by peculiar structural features and uncovers a new regulatory
      signaling path distinct from the MAPK signaling cascade and otherwise commonly
      activated by stress-related stimuli or various intracellular microbes. 

PMID- 24043762
TI  - ER stress transcription factor Xbp1 suppresses intestinal tumorigenesis and
      directs intestinal stem cells.
AB  - Unresolved endoplasmic reticulum (ER) stress in the epithelium can provoke
      intestinal inflammation. Hypomorphic variants of ER stress response mediators,
      such as X-box-binding protein 1 (XBP1), confer genetic risk for inflammatory
      bowel disease. We report here that hypomorphic Xbp1 function instructs a
      multilayered regenerative response in the intestinal epithelium. This is
      characterized by intestinal stem cell (ISC) expansion as shown by an inositol
      requiring enzyme 1alpha (Ire1alpha)-mediated increase in Lgr5(+) and Olfm4(+)
      ISCs and a Stat3-dependent increase in the proliferative output of transit
      amplifying cells. These consequences of hypomorphic Xbp1 function are associated
      with an increased propensity to develop colitis-associated and spontaneous
      adenomatous polyposis coli (APC)-related tumors of the intestinal epithelium,
      which in the latter case is shown to be dependent on Ire1alpha. This study
      reveals an unexpected role for Xbp1 in suppressing tumor formation through
      restraint of a pathway that involves an Ire1alpha- and Stat3-mediated
      regenerative response of the epithelium as a consequence of ER stress. As such,
      Xbp1 in the intestinal epithelium not only regulates local inflammation but at
      the same time also determines the propensity of the epithelium to develop tumors.

PMID- 24043763
TI  - Alveolar macrophages develop from fetal monocytes that differentiate into long
      lived cells in the first week of life via GM-CSF.
AB  - Tissue-resident macrophages can develop from circulating adult monocytes or from
      primitive yolk sac-derived macrophages. The precise ontogeny of alveolar
      macrophages (AMFs) is unknown. By performing BrdU labeling and parabiosis
      experiments in adult mice, we found that circulating monocytes contributed
      minimally to the steady-state AMF pool. Mature AMFs were undetectable before
      birth and only fully colonized the alveolar space by 3 d after birth. Before
      birth, F4/80(hi)CD11b(lo) primitive macrophages and Ly6C(hi)CD11b(hi) fetal
      monocytes sequentially colonized the developing lung around E12.5 and E16.5,
      respectively. The first signs of AMF differentiation appeared around the saccular
      stage of lung development (E18.5). Adoptive transfer identified fetal monocytes,
      and not primitive macrophages, as the main precursors of AMFs. Fetal monocytes
      transferred to the lung of neonatal mice acquired an AMF phenotype via defined
      developmental stages over the course of one week, and persisted for at least
      three months. Early AMF commitment from fetal monocytes was absent in GM-CSF
      deficient mice, whereas short-term perinatal intrapulmonary GM-CSF therapy
      rescued AMF development for weeks, although the resulting AMFs displayed an
      immature phenotype. This demonstrates that tissue-resident macrophages can also
      develop from fetal monocytes that adopt a stable phenotype shortly after birth in
      response to instructive cytokines, and then self-maintain throughout life. 

PMID- 24043764
TI  - Intestinal monocytes and macrophages are required for T cell polarization in
      response to Citrobacter rodentium.
AB  - Dendritic cells (DCs), monocytes, and macrophages are closely related phagocytes
      that share many phenotypic features and, in some cases, a common developmental
      origin. Although the requirement for DCs in initiating adaptive immune responses
      is well appreciated, the role of monocytes and macrophages remains largely
      undefined, in part because of the lack of genetic tools enabling their specific
      depletion. Here, we describe a two-gene approach that requires overlapping
      expression of LysM and Csf1r to define and deplete monocytes and macrophages. The
      role of monocytes and macrophages in immunity to pathogens was tested by their
      selective depletion during infection with Citrobacter rodentium. Although neither
      cell type was required to initiate immunity, monocytes and macrophages
      contributed to the adaptive immune response by secreting IL-12, which induced Th1
      polarization and IFN-gamma secretion. Thus, whereas DCs are indispensable for
      priming naive CD4(+) T cells, monocytes and macrophages participate in intestinal
      immunity by producing mediators that direct T cell polarization. 

PMID- 24043765
TI  - VEGF controls lung Th2 inflammation via the miR-1-Mpl (myeloproliferative
      leukemia virus oncogene)-P-selectin axis.
AB  - Asthma, the prototypic Th2-mediated inflammatory disorder of the lung, is an
      emergent disease worldwide. Vascular endothelial growth factor (VEGF) is a
      critical regulator of pulmonary Th2 inflammation, but the underlying mechanism
      and the roles of microRNAs (miRNAs) in this process have not been defined. Here
      we show that lung-specific overexpression of VEGF decreases miR-1 expression in
      the lung, most prominently in the endothelium, and a similar down-regulation
      occurs in lung endothelium in Th2 inflammation models. Intranasal delivery of miR
      1 inhibited inflammatory responses to ovalbumin, house dust mite, and IL-13
      overexpression. Blocking VEGF inhibited Th2-mediated lung inflammation, and this
      was restored by antagonizing miR-1. Using mRNA arrays, Argonaute pull-down
      assays, luciferase expression assays, and mutational analysis, we identified Mpl
      as a direct target of miR-1 and showed that VEGF controls the expression of
      endothelial Mpl during Th2 inflammation via the regulation of miR-1. In vivo
      knockdown of Mpl inhibited Th2 inflammation and indirectly inhibited the
      expression of P-selectin in lung endothelium. These experiments define a novel
      VEGF-miR-1-Mpl-P-selectin effector pathway in lung Th2 inflammation and herald
      the utility of miR-1 and Mpl as potential therapeutic targets for asthma. 

PMID- 24043766
TI  - Homologous RIG-I-like helicase proteins direct RNAi-mediated antiviral immunity
      in C. elegans by distinct mechanisms.
AB  - RNAi-mediated antiviral immunity in Caenorhabditis elegans requires Dicer-related
      helicase 1 (DRH-1), which encodes the helicase and C-terminal domains homologous
      to the mammalian retinoic acid inducible gene I (RIG-I)-like helicase (RLH)
      family of cytosolic immune receptors. Here we show that the antiviral function of
      DRH-1 requires the RIG-I homologous domains as well as its worm-specific N
      terminal domain. We also demonstrate that the helicase and C-terminal domains
      encoded by either worm DRH-2 or human RIG-I can functionally replace the
      corresponding domains of DRH-1 to mediate antiviral RNAi in C. elegans. Notably,
      substitutions in a three-residue motif of the C-terminal regulatory domain of RIG
      I that physically interacts with viral double-stranded RNA abolish the antiviral
      activity of C-terminal regulatory domains of both RIG-I and DRH-1 in C. elegans.
      Genetic analysis revealed an essential role for both DRH-1 and DRH-3 in C.
      elegans antiviral RNAi targeting a natural viral pathogen. However, Northern blot
      and small RNA deep sequencing analyses indicate that DRH-1 acts to enhance
      production of viral primary siRNAs, whereas DRH-3 regulates antiviral RNAi by
      participating in the biogenesis of secondary siRNAs after Dicer-dependent
      production of primary siRNAs. We propose that DRH-1 facilitates the acquisition
      of viral double-stranded RNA by the worm dicing complex for the subsequent
      processing into primary siRNAs. The strong parallel for the antiviral function of
      RLHs in worms and mammals suggests that detection of viral double-stranded RNA
      may activate completely unrelated effector mechanisms or, alternatively, that the
      mammalian RLHs have a conserved activity to stimulate production of viral siRNAs
      for antiviral immunity by an RNAi effector mechanism. 

PMID- 24043767
TI  - Why abundant tropical tree species are phylogenetically old.
AB  - Neutral models of species diversity predict patterns of abundance for communities
      in which all individuals are ecologically equivalent. These models were
      originally developed for Panamanian trees and successfully reproduce observed
      distributions of abundance. Neutral models also make macroevolutionary
      predictions that have rarely been evaluated or tested. Here we show that neutral
      models predict a humped or flat relationship between species age and population
      size. In contrast, ages and abundances of tree species in the Panamanian Canal
      watershed are found to be positively correlated, which falsifies the models.
      Speciation rates vary among phylogenetic lineages and are partially heritable
      from mother to daughter species. Variable speciation rates in an otherwise
      neutral model lead to a demographic advantage for species with low speciation
      rate. This demographic advantage results in a positive correlation between
      species age and abundance, as found in the Panamanian tropical forest community. 

PMID- 24043768
TI  - De novo expression of connexin hemichannels in denervated fast skeletal muscles
      leads to atrophy.
AB  - Denervation of skeletal muscles induces atrophy, preceded by changes in
      sarcolemma permeability of causes not yet completely understood. Here, we show
      that denervation-induced Evans blue dye uptake in vivo of fast, but not slow,
      myofibers was acutely inhibited by connexin (Cx) hemichannel/pannexin1 (Panx1)
      channel and purinergic ionotropic P2X7 receptor (P2X7R) blockers. Denervated
      myofibers showed up-regulation of Panx1 and de novo expression of Cx39, Cx43, and
      Cx45 hemichannels as well as P2X7Rs and transient receptor potential subfamily V,
      member 2, channels, all of which are permeable to small molecules. The sarcolemma
      of freshly isolated WT myofibers from denervated muscles also showed high
      hemichannel-mediated permeability that was slightly reduced by blockade of Panx1
      channels or the lack of Panx1 expression, but was completely inhibited by Cx
      hemichannel or P2X7R blockers, as well as by degradation of extracellular ATP.
      However, inhibition of transient receptor potential subfamily V, member 2,
      channels had no significant effect on membrane permeability. Moreover, activation
      of the transcription factor NFkappaB and higher mRNA levels of proinflammatory
      cytokines (TNF-alpha and IL-1beta) were found in denervated WT but not Cx43/Cx45
      deficient muscles. The atrophy observed after 7 d of denervation was drastically
      reduced in Cx43/Cx45-deficient but not Panx1-deficient muscles. Therefore,
      expression of Cx hemichannels and P2X7R promotes a feed-forward mechanism
      activated by extracellular ATP, most likely released through hemichannels, that
      activates the inflammasome. Consequently, Cx hemichannels are potential targets
      for new therapeutic agents to prevent or reduce muscle atrophy induced by
      denervation of diverse etiologies. 

PMID- 24043769
TI  - TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted
      therapeutic strategy in lenalidomide-resistant patients.
AB  - Stabilization of p53 in erythroid precursors in response to nucleosomal stress
      underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with
      chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically
      active 20-mer antisense oligonucleotide complementary to TP53 exon10, could
      suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen
      treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced
      cellular p53 and p53-up-regulated modulator of apoptosis expression compared with
      controls, accompanied by a significant reduction in apoptosis and increased cell
      proliferation. In a two-stage erythroid differentiation assay, cenersen
      significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from
      patients with del(5q) MDS, whereas erythroid burst recovery increased
      proportionally to the magnitude of p53 suppression without evidence of del(5q)
      clonal suppression (r = -0.6; P = 0.005). To explore the effect of p53
      suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor
      dependent p53 antagonist, was added to lenalidomide treatment in eight lower
      risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance.
      Transfusion independence was restored in five patients accompanied by expansion
      of erythroid precursors and decreased cellular p53 expression. We conclude that
      targeted suppression of p53 could support effective erythropoiesis in
      lenalidomide-resistant del(5q) MDS. 

PMID- 24043770
TI  - Synthetic polyubiquitinated alpha-Synuclein reveals important insights into the
      roles of the ubiquitin chain in regulating its pathophysiology.
AB  - Ubiquitination regulates, via different modes of modifications, a variety of
      biological processes, and aberrations in the process have been implicated in the
      pathogenesis of several neurodegenerative diseases. However, our ability to
      dissect the pathophysiological relevance of the ubiquitination code has been
      hampered due to the lack of methods that allow site-specific introduction of
      ubiquitin (Ub) chains to a specific substrate. Here, we describe chemical and
      semisynthetic strategies for site-specific incorporation of K48-linked di- or
      tetra-Ub chains onto the side chain of Lys12 of alpha-Synuclein (alpha-Syn).
      These advances provided unique opportunities to elucidate the role of
      ubiquitination and Ub chain length in regulating alpha-Syn stability,
      aggregation, phosphorylation, and clearance. In addition, we investigated the
      cross-talk between phosphorylation and ubiquitination, the two most common alpha
      Syn pathological modifications identified within Lewy bodies and Parkinson
      disease. Our results suggest that alpha-Syn functions under complex regulatory
      mechanisms involving cross-talk among different posttranslational modifications. 

PMID- 24043771
TI  - Natural killer T (NKT)-B-cell interactions promote prolonged antibody responses
      and long-term memory to pneumococcal capsular polysaccharides.
AB  - Innate-like natural killer T (NKT) cells critically enhance cell and humoral
      immunity against infections through recognition of conserved microbial lipid
      antigens presented by CD1d-expressing antigen-presenting cells, and provision of
      CD40L and cytokine signals. Whereas NKT cells efficiently licensed dendritic
      cells to prime potent effector and memory T cells, studies based on model
      antigens such as alphagalactosylceramide-nitrophenyl conjugates concluded that
      help to B cells was associated with NKT follicular helper differentiation, but
      limited to short-term responses without induction of memory. We revisited this
      surprising conclusion in the context of the extracellular encapsulated pathogen
      Streptococcus pneumoniae, where recognition of lipid and capsular polysaccharide
      antigens by NKT cells and B cells, respectively, provide critical host
      protection. Using liposomal nanoparticles displaying synthetic lipid and
      polysaccharide antigens to elicit pure and direct NKT-B-cell interactions in
      vivo, we observed intense and prolonged antibody responses with isotype switch,
      affinity maturation, and long-lasting B-cell memory, despite modest or absent NKT
      follicular helper differentiation. Furthermore, conditional ablation of Cd1d
      demonstrated a requirement for a two-step process involving first cognate
      interactions with dendritic cells, for NKT cell activation, and then with B
      cells, for induction of isotype switch and memory. Thus, NKT help to B cells
      represents both a major arm of antimicrobial defense and a promising target for B
      cell vaccines. 

PMID- 24043772
TI  - A set of genes critical to development is epigenetically poised in mouse germ
      cells from fetal stages through completion of meiosis.
AB  - In multicellular organisms, germ cells carry the hereditary material from one
      generation to the next. Developing germ cells are unipotent gamete precursors,
      and mature gametes are highly differentiated, specialized cells. However, upon
      gamete union at fertilization, their genomes drive a totipotent program, giving
      rise to a complete embryo as well as extraembryonic tissues. The biochemical
      basis for the ability to transition from differentiated cell to totipotent zygote
      is unknown. Here we report that a set of developmentally critical genes is
      maintained in an epigenetically poised (bivalent) state from embryonic stages
      through the end of meiosis. We performed ChIP-seq and RNA-seq analysis on flow
      sorted male and female germ cells during embryogenesis at three time points
      surrounding sexual differentiation and female meiotic initiation, and then
      extended our analysis to meiotic and postmeiotic male germ cells. We identified a
      set of genes that is highly enriched for regulators of differentiation and
      retains a poised state (high H3K4me3, high H3K27me3, and lack of expression)
      across sexes and across developmental stages, including in haploid postmeiotic
      cells. The existence of such a state in embryonic stem cells has been well
      described. We now demonstrate that a subset of genes is maintained in a poised
      state in the germ line from the initiation of sexual differentiation during fetal
      development and into postmeiotic stages. We propose that the epigenetically
      poised condition of these developmental genes is a fundamental property of the
      mammalian germ-line nucleus, allowing differentiated gametes to unleash a
      totipotent program following fertilization. 

PMID- 24043773
TI  - Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves.
AB  - Treatments with two-small molecule tropomyosin receptor kinase B (trkB) ligands,
      7,8 dihydroxyflavone (7,8 DHF) and deoxygedunin, were evaluated for their ability
      to promote the regeneration of cut axons in injured peripheral nerves in mice in
      which sensory and motor axons are marked by YFP. Peripheral nerves were cut and
      repaired with grafts from strain-matched, nonfluorescent donors and secured in
      place with fibrin glue. Lengths of profiles of regenerating YFP(+) axons were
      measured 2 wk later from confocal images. Axon regeneration was enhanced when the
      fibrin glue contained dilutions of 500-nM solution of either small-molecule trkB
      agonist. In mice in which the neurotrophin receptor trkB is knocked out
      selectively in neurons, axon regeneration is very weak, and topical treatment
      with 7,8 DHF had no effect on axon regeneration. Similar treatments with
      deoxygedunin had only a modest effect. In conditional BDNF knockout mice, topical
      treatments with either 7,8 DHF or deoxygedunin resulted in a reversal of the poor
      regeneration found in controls and produced significant enhancement of
      regeneration. In WT mice treated with 2 wk of daily i.p. injections of either 7,8
      DHF or deoxygedunin (5 mg/kg), regenerating axon profiles were nearly twice as
      long as in controls. Restoration of direct muscle responses evoked by sciatic
      nerve stimulation to pretransection levels over an 8-wk survival period was found
      only in the treated mice. Treatments with either small-molecule trkB agonist
      enhanced axon regeneration and muscle reinnervation after peripheral nerve
      injuries. 

PMID- 24043774
TI  - Active output state of the Synechococcus Kai circadian oscillator.
AB  - The mechanisms by which cellular oscillators keep time and transmit temporal
      information are poorly understood. In cyanobacteria, the timekeeping aspect of
      the circadian oscillator, composed of the KaiA, KaiB, and KaiC proteins, involves
      a cyclic progression of phosphorylation states at Ser431 and Thr432 of KaiC.
      Elucidating the mechanism that uses this temporal information to modulate gene
      expression is complicated by unknowns regarding the number, structure, and
      regulatory effects of output components. To identify oscillator signaling states
      without a complete description of the output machinery, we defined a simple
      metric, Kai-complex output activity (KOA), that represents the difference in
      expression of reporter genes between strains that carry specific variants of KaiC
      and baseline strains that lack KaiC. In the absence of the oscillator, expression
      of the class 1 paradigm promoter P(kaiBC) was locked at its usual peak level;
      conversely, that of the class 2 paradigm promoter P(purF) was locked at its
      trough level. However, for both classes of promoters, peak KOA in wild-type
      strains coincided late in the circadian cycle near subjective dawn, when KaiC-pST
      becomes most prevalent (Ser431 is phosphorylated and Thr432 is not). Analogously,
      peak KOA was detected specifically for the phosphomimetic of KaiC-pST (KaiC-ET).
      Notably, peak KOA required KaiB, indicating that a KaiBC complex is involved in
      the output activity. We also found evidence that phosphorylated RpaA (regulator
      of phycobilisome associated) represses an RpaA-independent output of KOA. A
      simple mathematical expression successfully simulated two key features of the
      oscillator-the time of peak KOA and the peak-to-trough amplitude changes.

PMID- 24043775
TI  - Atypical mitochondrial fission upon bacterial infection.
AB  - We recently showed that infection by Listeria monocytogenes causes mitochondrial
      network fragmentation through the secreted pore-forming toxin listeriolysin O
      (LLO). Here, we examine factors involved in canonical fusion and fission.
      Strikingly, LLO-induced mitochondrial fragmentation does not require the
      traditional fission machinery, as Drp1 oligomers are absent from fragmented
      mitochondria following Listeria infection or LLO treatment, as the dynamin-like
      protein 1 (Drp1) receptor Mff is rapidly degraded, and as fragmentation proceeds
      efficiently in cells with impaired Drp1 function. LLO does not cause processing
      of the fusion protein optic atrophy protein 1 (Opa1), despite inducing a decrease
      in the mitochondrial membrane potential, suggesting a unique Drp1- and Opa1
      independent fission mechanism distinct from that triggered by uncouplers or the
      apoptosis inducer staurosporine. We show that the ER marks LLO-induced
      mitochondrial fragmentation sites even in the absence of functional Drp1,
      demonstrating that the ER activity in regulating mitochondrial fission can be
      induced by exogenous agents and that the ER appears to regulate fission by a
      mechanism independent of the canonical mitochondrial fission machinery. 

PMID- 24043776
TI  - Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways.
AB  - The ability to maintain proper airway surface liquid (ASL) volume homeostasis is
      vital for mucus hydration and clearance, which are essential aspects of the
      mammalian lung's innate defense system. In cystic fibrosis (CF), one of the most
      common life-threatening genetic disorders, ASL dehydration leads to mucus
      accumulation and chronic infection. In normal airways, the secreted protein short
      palate lung and nasal epithelial clone 1 (SPLUNC1) effectively inhibits
      epithelial Na(+) channel (ENaC)-dependent Na(+) absorption and preserves ASL
      volume. In CF airways, it has been hypothesized that increased ENaC-dependent
      Na(+) absorption contributes to ASL depletion, and hence increased disease.
      However, this theory is controversial, and the mechanism for abnormal ENaC
      regulation in CF airways has remained elusive. Here, we show that SPLUNC1 is a pH
      sensitive regulator of ENaC and is unable to inhibit ENaC in the acidic CF airway
      environment. Alkalinization of CF airway cultures prevented CF ASL
      hyperabsorption, and this effect was abolished when SPLUNC1 was stably knocked
      down. Accordingly, we resolved the crystal structure of SPLUNC1 to 2.8 A.
      Notably, this structure revealed two pH-sensitive salt bridges that, when
      removed, rendered SPLUNC1 pH-insensitive and able to regulate ASL volume in
      acidic ASL. Thus, we conclude that ENaC hyperactivity is secondary to reduced CF
      ASL pH. Together, these data provide molecular insights into the mucosal
      dehydration associated with a range of pulmonary diseases, including CF, and
      suggest that future therapy be directed toward alkalinizing the pH of CF airways.

PMID- 24043777
TI  - Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic
      DNA structural changes and NEK2 as a new disease gene.
AB  - We performed whole genome sequencing in 16 unrelated patients with autosomal
      recessive retinitis pigmentosa (ARRP), a disease characterized by progressive
      retinal degeneration and caused by mutations in over 50 genes, in search of
      pathogenic DNA variants. Eight patients were from North America, whereas eight
      were Japanese, a population for which ARRP seems to have different genetic
      drivers. Using a specific workflow, we assessed both the coding and noncoding
      regions of the human genome, including the evaluation of highly polymorphic SNPs,
      structural and copy number variations, as well as 69 control genomes sequenced by
      the same procedures. We detected homozygous or compound heterozygous mutations in
      7 genes associated with ARRP (USH2A, RDH12, CNGB1, EYS, PDE6B, DFNB31, and CERKL)
      in eight patients, three Japanese and five Americans. Fourteen of the 16 mutant
      alleles identified were previously unknown. Among these, there was a 2.3-kb
      deletion in USH2A and an inverted duplication of ~446 kb in EYS, which would have
      likely escaped conventional screening techniques or exome sequencing. Moreover,
      in another Japanese patient, we identified a homozygous frameshift (p.L206fs),
      absent in more than 2,500 chromosomes from ethnically matched controls, in the
      ciliary gene NEK2, encoding a serine/threonine-protein kinase. Inactivation of
      this gene in zebrafish induced retinal photoreceptor defects that were rescued by
      human NEK2 mRNA. In addition to identifying a previously undescribed ARRP gene,
      our study highlights the importance of rare structural DNA variations in
      Mendelian diseases and advocates the need for screening approaches that transcend
      the analysis of the coding sequences of the human genome.

PMID- 24043778
TI  - Probing the protein-folding mechanism using denaturant and temperature effects on
      rate constants.
AB  - Protein folding has been extensively studied, but many questions remain regarding
      the mechanism. Characterizing early unstable intermediates and the high-free
      energy transition state (TS) will help answer some of these. Here, we use effects
      of denaturants (urea, guanidinium chloride) and temperature on folding and
      unfolding rate constants and the overall equilibrium constant as probes of
      surface area changes in protein folding. We interpret denaturant kinetic m-values
      and activation heat capacity changes for 13 proteins to determine amounts of
      hydrocarbon and amide surface buried in folding to and from TS, and for complete
      folding. Predicted accessible surface area changes for complete folding agree in
      most cases with structurally determined values. We find that TS is advanced (50
      90% of overall surface burial) and that the surface buried is disproportionately
      amide, demonstrating extensive formation of secondary structure in early
      intermediates. Models of possible pre-TS intermediates with all elements of the
      native secondary structure, created for several of these proteins, bury less
      amide and hydrocarbon surface than predicted for TS. Therefore, we propose that
      TS generally has both the native secondary structure and sufficient organization
      of other regions of the backbone to nucleate subsequent (post-TS) formation of
      tertiary interactions. The approach developed here provides proof of concept for
      the use of denaturants and other solutes as probes of amount and composition of
      the surface buried in coupled folding and other large conformational changes in
      TS and intermediates in protein processes. 

PMID- 24043779
TI  - Programmed cell death 1 inhibits inflammatory helper T-cell development through
      controlling the innate immune response.
AB  - Programmed cell death 1 (PD-1) is an inhibitory coreceptor on immune cells and is
      essential for self-tolerance because mice genetically lacking PD-1 (PD-1(-/-))
      develop spontaneous autoimmune diseases. PD-1(-/-) mice are also susceptible to
      severe experimental autoimmune encephalomyelitis (EAE), characterized by a
      massive production of effector/memory T cells against myelin autoantigen, the
      mechanism of which is not fully understood. We found that an increased primary
      response of PD-1(-/-) mice to heat-killed mycobacteria (HKMTB), an adjuvant for
      EAE, contributed to the enhanced production of T-helper 17 (Th17) cells.
      Splenocytes from HKMTB-immunized, lymphocyte-deficient PD-1(-/-) recombination
      activating gene (RAG)2(-/-) mice were found to drive antigen-specific Th17 cell
      differentiation more efficiently than splenocytes from HKMTB-immunized PD-1(+/+)
      RAG2(-/-) mice. This result suggested PD-1's involvement in the regulation of
      innate immune responses. Mice reconstituted with PD-1(-/-) RAG2(-/-) bone marrow
      and PD-1(+/+) CD4(+) T cells developed more severe EAE compared with the ones
      reconstituted with PD-1(+/+) RAG2(-/-) bone marrow and PD-1(+/+) CD4(+) T cells.
      We found that upon recognition of HKMTB, CD11b(+) macrophages from PD-1(-/-) mice
      produced very high levels of IL-6, which helped promote naive CD4(+) T-cell
      differentiation into IL-17-producing cells. We propose a model in which PD-1
      negatively regulates antimycobacterial responses by suppressing innate immune
      cells, which in turn prevents autoreactive T-cell priming and differentiation to
      inflammatory effector T cells. 

PMID- 24043780
TI  - ECHIDNA-mediated post-Golgi trafficking of auxin carriers for differential cell
      elongation.
AB  - The plant hormone indole-acetic acid (auxin) is essential for many aspects of
      plant development. Auxin-mediated growth regulation typically involves the
      establishment of an auxin concentration gradient mediated by polarly localized
      auxin transporters. The localization of auxin carriers and their amount at the
      plasma membrane are controlled by membrane trafficking processes such as
      secretion, endocytosis, and recycling. In contrast to endocytosis or recycling,
      how the secretory pathway mediates the localization of auxin carriers is not well
      understood. In this study we have used the differential cell elongation process
      during apical hook development to elucidate the mechanisms underlying the post
      Golgi trafficking of auxin carriers in Arabidopsis. We show that differential
      cell elongation during apical hook development is defective in Arabidopsis mutant
      echidna (ech). ECH protein is required for the trans-Golgi network (TGN)-mediated
      trafficking of the auxin influx carrier AUX1 to the plasma membrane. In contrast,
      ech mutation only marginally perturbs the trafficking of the highly related auxin
      influx carrier LIKE-AUX1-3 or the auxin efflux carrier PIN-FORMED-3, both also
      involved in hook development. Electron tomography reveals that the trafficking
      defects in ech mutant are associated with the perturbation of secretory vesicle
      genesis from the TGN. Our results identify differential mechanisms for the post
      Golgi trafficking of de novo-synthesized auxin carriers to plasma membrane from
      the TGN and reveal how trafficking of auxin influx carriers mediates the control
      of differential cell elongation in apical hook development. 

PMID- 24043781
TI  - SUMOylation is essential for sex-specific assembly and function of the
      Caenorhabditis elegans dosage compensation complex on X chromosomes.
AB  - The essential process of dosage compensation equalizes X-chromosome gene
      expression between Caenorhabditis elegans XO males and XX hermaphrodites through
      a dosage compensation complex (DCC) that is homologous to condensin. The DCC
      binds to both X chromosomes of hermaphrodites to repress transcription by half.
      Here, we show that posttranslational modification by the SUMO (small ubiquitin
      like modifier) conjugation pathway is essential for sex-specific assembly and
      function of the DCC on X. Depletion of SUMO in vivo severely disrupts binding of
      particular DCC subunits and causes changes in X-linked gene expression similar to
      those caused by deleting genes encoding DCC subunits. Three DCC subunits are
      SUMOylated, and SUMO depletion preferentially reduces their binding to X,
      suggesting that SUMOylation of DCC subunits is essential for robust association
      with X. DCC SUMOylation is triggered by the signal that initiates DCC assembly
      onto X. The initial step of assembly-binding of X-targeting factors to
      recruitment sites on X-is independent of SUMOylation, but robust binding of the
      complete complex requires SUMOylation. SUMOylated DCC subunits are enriched at
      recruitment sites, and SUMOylation likely enhances interactions between X
      targeting factors and condensin subunits that facilitate DCC binding beyond the
      low level achieved without SUMOylation. DCC subunits also participate in
      condensin complexes essential for chromosome segregation, but their SUMOylation
      occurs only in the context of the DCC. Our results reinforce a newly emerging
      theme in which multiple proteins of a complex are collectively SUMOylated in
      response to a specific stimulus, leading to accelerated complex formation and
      enhanced function. 

PMID- 24043782
TI  - Key features of sigmaS required for specific recognition by Crl, a transcription
      factor promoting assembly of RNA polymerase holoenzyme.
AB  - Bacteria use multiple sigma factors to coordinate gene expression in response to
      environmental perturbations. In Escherichia coli and other gamma-proteobacteria,
      the transcription factor Crl stimulates sigma(S)-dependent transcription during
      times of cellular stress by promoting the association of sigma(S) with core RNA
      polymerase. The molecular basis for specific recognition of sigma(S) by Crl,
      rather than the homologous and more abundant primary sigma factor sigma(70), is
      unknown. Here we use bacterial two-hybrid analysis in vivo and p-benzoyl
      phenylalanine cross-linking in vitro to define the features in sigma(S)
      responsible for specific recognition by Crl. We identify residues in sigma(S)
      conserved domain 2 (sigma(S)2) that are necessary and sufficient to allow
      recognition of sigma(70) conserved domain 2 by Crl, one near the promoter-melting
      region and the other at the position where a large nonconserved region interrupts
      the sequence of sigma(70). We then use luminescence resonance energy transfer to
      demonstrate directly that Crl promotes holoenzyme assembly using these
      specificity determinants on sigma(S). Our results explain how Crl distinguishes
      between sigma factors that are largely homologous and activates discrete sets of
      promoters even though it does not bind to promoter DNA. 

PMID- 24043783
TI  - Actin-related protein2/3 complex regulates tight junctions and terminal
      differentiation to promote epidermal barrier formation.
AB  - The epidermis provides an essential seal from the external environment and
      retains fluids within the body. To form an effective barrier, cells in the
      epidermis must form tight junctions and terminally differentiate into cornified
      envelopes. Here, we demonstrate that the branched actin nucleator, the actin
      related protein (Arp)2/3 complex, is unexpectedly required for both these
      activities. Loss of the ArpC3 subunit of the Arp2/3 complex resulted in minimal
      changes in the morphogenesis and architecture of this stratified squamous
      epithelium, but resulted in profound defects in its physiology. Mutant embryos
      did not develop an effective barrier to the external environment and died within
      hours of birth. We discovered two underlying causes for these effects. First,
      ArpC3 was essential for robust assembly and function of tight junctions,
      specialized cell-cell adhesions that restrict water loss in the epidermis.
      Second, there were defects in differentiation of the epidermis and the production
      of cornified envelopes, structures essential for barrier activity. Underlying
      this defect, we found that YAP was inappropriately active not only in the ArpC3
      mutant tissue, but also in cultured cells. Inhibition of YAP activity rescued the
      differentiation and barrier defects caused by loss of ArpC3. These results
      demonstrate previously unappreciated roles for the Arp2/3 complex and highlight
      the functions of branched actin networks in a complex tissue. 

PMID- 24043784
TI  - Organellar oligopeptidase (OOP) provides a complementary pathway for targeting
      peptide degradation in mitochondria and chloroplasts.
AB  - Both mitochondria and chloroplasts contain distinct proteolytic systems for
      precursor protein processing catalyzed by the mitochondrial and stromal
      processing peptidases and for the degradation of targeting peptides catalyzed by
      presequence protease. Here, we have identified and characterized a component of
      the organellar proteolytic systems in Arabidopsis thaliana, the organellar
      oligopeptidase, OOP (At5g65620). OOP belongs to the M3A family of peptide
      degrading metalloproteases. Using two independent in vivo methods, we show that
      the protease is dually localized to mitochondria and chloroplasts. Furthermore,
      we localized the OPP homolog At5g10540 to the cytosol. Analysis of peptide
      degradation by OOP revealed substrate size restriction from 8 to 23 aa residues.
      Short mitochondrial targeting peptides (presequence of the ribosomal protein L29
      and presequence of 1-aminocyclopropane-1-carboxylic acid deaminase 1) and N- and
      C-terminal fragments derived from the presequence of the ATPase beta subunit
      ranging in size from 11 to 20 aa could be degraded. MS analysis showed that OOP
      does not exhibit a strict cleavage pattern but shows a weak preference for
      hydrophobic residues (F/L) at the P1 position. The crystal structures of OOP, at
      1.8-1.9 A, exhibit an ellipsoidal shape consisting of two major domains enclosing
      the catalytic cavity of 3,000 A(3). The structural and biochemical data suggest
      that the protein undergoes conformational changes to allow peptide binding and
      proteolysis. Our results demonstrate the complementary role of OOP in targeting
      peptide degradation in mitochondria and chloroplasts. 

PMID- 24043785
TI  - Regulated structural transitions unleash the chaperone activity of alphaB
      crystallin.
AB  - The small heat shock protein alphaB-crystallin is an oligomeric molecular
      chaperone that binds aggregation-prone proteins. As a component of the
      proteostasis system, it is associated with cataract, neurodegenerative diseases,
      and myopathies. The structural determinants for the regulation of its chaperone
      function are still largely elusive. Combining different experimental approaches,
      we show that phosphorylation-induced destabilization of intersubunit interactions
      mediated by the N-terminal domain (NTD) results in the remodeling of the oligomer
      ensemble with an increase in smaller, activated species, predominantly 12-mers
      and 6-mers. Their 3D structures determined by cryo-electron microscopy and
      biochemical analyses reveal that the NTD in these species gains flexibility and
      solvent accessibility. These modulated properties are accompanied by an increase
      in chaperone activity in vivo and in vitro and a more efficient cooperation with
      the heat shock protein 70 system in client folding. Thus, the modulation of the
      structural flexibility of the NTD, as described here for phosphorylation, appears
      to regulate the chaperone activity of alphaB-crystallin rendering the NTD a
      conformational sensor for nonnative proteins. 

PMID- 24043786
TI  - Regulation of human hematopoietic stem cell self-renewal by the
      microenvironment's control of retinoic acid signaling.
AB  - The high expression of aldehyde dehydrogenase 1, also known as retinaldehyde
      dehydrogenase, by hematopoietic stem cells (HSCs) suggests an important role for
      retinoic acid (RA) signaling in determining the fate of these cells. We found
      that primitive human bone marrow-derived CD34(+)CD38(-) cells not only highly
      express aldehyde dehydrogenase 1, but also the RA receptor alpha. Despite the up
      regulation of early components of RA signaling, the downstream pathway remained
      inactive in the primitive CD34(+)CD38(-) cells. Primitive hematopoietic cells
      rapidly undergo terminal differentiation when cultured away from their
      microenvironment; however, we found that inhibition of RA signaling maintained
      their primitive phenotype and function, and promoted their self-renewal. HSCs
      reside in a complex microenvironment that enforces the balance between self
      renewal and differentiation. The exact physiologic mechanisms by which the niche
      controls HSC fate remain elusive. The embryonic gonadal microenvironment has
      recently been shown to determine germ-cell fate by degrading RA through
      expression of the P450 retinoid-inactivating enzyme CYP26B1. We found that the
      bone marrow microenvironment similarly can control primitive hematopoietic cell
      fate via modulation of retinoid bioavailability. Accordingly, we found that bone
      marrow stromal cell CYP26 was also able to inactivate retinoids in serum,
      preventing RA signaling. Thus, primitive hematopoietic cells appear to be
      intrinsically programmed to undergo RA-mediated differentiation unless prevented
      from doing so by bone marrow niche CYP26. Modulation of RA signaling also holds
      promise for clinical HSC expansion, a prerequisite for the wide-scale use of
      these cells in regenerative medicine and gene therapy. 

PMID- 24043787
TI  - Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism
      without impaired glucose homeostasis.
AB  - Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin,
      and Betatrophin) is a newly recognized ANGPTL family member that has been
      implicated in both triglyceride (TG) and glucose metabolism. Hepatic
      overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin
      secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose
      metabolism in mice. Angptl8 knockout (Angptl8(-/-)) mice gained weight more
      slowly than wild-type littermates due to a selective reduction in adipose tissue
      accretion. Plasma levels of TGs of the Angptl8(-/-) mice were similar to wild
      type animals in the fasted state but paradoxically decreased after refeeding. The
      lower TG levels were associated with both a reduction in very low density
      lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity.
      Despite the increase in LPL activity, the uptake of very low density lipoprotein
      TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8(
      /-) mice. Taken together, these data indicate that ANGPTL8 plays a key role in
      the metabolic transition between fasting and refeeding; it is required to direct
      fatty acids to adipose tissue for storage in the fed state. Finally, glucose and
      insulin tolerance testing revealed no alterations in glucose homeostasis in mice
      fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly
      disrupts TG metabolism, we found no evidence that it is required for maintenance
      of glucose homeostasis. 

PMID- 24043789
TI  - Human and natural influences on the changing thermal structure of the atmosphere.
AB  - Since the late 1970s, satellite-based instruments have monitored global changes
      in atmospheric temperature. These measurements reveal multidecadal tropospheric
      warming and stratospheric cooling, punctuated by short-term volcanic signals of
      reverse sign. Similar long- and short-term temperature signals occur in model
      simulations driven by human-caused changes in atmospheric composition and natural
      variations in volcanic aerosols. Most previous comparisons of modeled and
      observed atmospheric temperature changes have used results from individual models
      and individual observational records. In contrast, we rely on a large multimodel
      archive and multiple observational datasets. We show that a human-caused
      latitude/altitude pattern of atmospheric temperature change can be identified
      with high statistical confidence in satellite data. Results are robust to current
      uncertainties in models and observations. Virtually all previous research in this
      area has attempted to discriminate an anthropogenic signal from internal
      variability. Here, we present evidence that a human-caused signal can also be
      identified relative to the larger "total" natural variability arising from
      sources internal to the climate system, solar irradiance changes, and volcanic
      forcing. Consistent signal identification occurs because both internal and total
      natural variability (as simulated by state-of-the-art models) cannot produce
      sustained global-scale tropospheric warming and stratospheric cooling. Our
      results provide clear evidence for a discernible human influence on the thermal
      structure of the atmosphere. 

PMID- 24043788
TI  - Critical role of segment-specific packaging signals in genetic reassortment of
      influenza A viruses.
AB  - The fragmented nature of the influenza A genome allows the exchange of gene
      segments when two or more influenza viruses infect the same cell, but little is
      known about the rules underlying this process. Here, we studied genetic
      reassortment between the A/Moscow/10/99 (H3N2, MO) virus originally isolated from
      human and the avian A/Finch/England/2051/91 (H5N2, EN) virus and found that this
      process is strongly biased. Importantly, the avian HA segment never entered the
      MO genetic background alone but always was accompanied by the avian PA and M
      fragments. Introduction of the 5' and 3' packaging sequences of HA(MO) into an
      otherwise HA(EN) backbone allowed efficient incorporation of the chimerical viral
      RNA (vRNA) into the MO genetic background. Furthermore, forcing the incorporation
      of the avian M segment or introducing five silent mutations into the human M
      segment was sufficient to drive coincorporation of the avian HA segment into the
      MO genetic background. These silent mutations also strongly affected the genotype
      of reassortant viruses. Taken together, our results indicate that packaging
      signals are crucial for genetic reassortment and that suboptimal compatibility
      between the vRNA packaging signals, which are detected only when vRNAs compete
      for packaging, limit this process.

PMID- 24043790
TI  - Template-constrained macrocyclic peptides prepared from native, unprotected
      precursors.
AB  - Peptide-protein interactions are important mediators of cellular-signaling
      events. Consensus binding motifs (also known as short linear motifs) within these
      contacts underpin molecular recognition, yet have poor pharmacological properties
      as discrete species. Here, we present methods to transform intact peptides into
      stable, templated macrocycles. Two simple steps install the template. The key
      reaction is a palladium-catalyzed macrocyclization. The catalysis has broad scope
      and efficiently forms large rings by engaging native peptide functionality
      including phenols, imidazoles, amines, and carboxylic acids without the necessity
      of protecting groups. The tunable reactivity of the template gives the process
      special utility. Defined changes in reaction conditions markedly alter
      chemoselectivity. In all cases examined, cyclization occurs rapidly and in high
      yield at room temperature, regardless of peptide composition or chain length. We
      show that conformational restraints imparted by the template stabilize secondary
      structure and enhance proteolytic stability in vitro. Palladium-catalyzed
      internal cinnamylation is a strong complement to existing methods for peptide
      modification. 

PMID- 24043791
TI  - Reverse genetics with a full-length infectious cDNA of the Middle East
      respiratory syndrome coronavirus.
AB  - Severe acute respiratory syndrome with high mortality rates (~50%) is associated
      with a novel group 2c betacoronavirus designated Middle East respiratory syndrome
      coronavirus (MERS-CoV). We synthesized a panel of contiguous cDNAs that spanned
      the entire genome. Following contig assembly into genome-length cDNA, transfected
      full-length transcripts recovered several recombinant viruses (rMERS-CoV) that
      contained the expected marker mutations inserted into the component clones.
      Because the wild-type MERS-CoV contains a tissue culture-adapted T1015N mutation
      in the S glycoprotein, rMERS-CoV replicated ~0.5 log less efficiently than wild
      type virus. In addition, we ablated expression of the accessory protein ORF5
      (rMERS*ORF5) and replaced it with tomato red fluorescent protein (rMERS-RFP) or
      deleted the entire ORF3, 4, and 5 accessory cluster (rMERS-DeltaORF3-5).
      Recombinant rMERS-CoV, rMERS-CoV*ORF5, and MERS-CoV-RFP replicated to high
      titers, whereas MERS-DeltaORF3-5 showed 1-1.5 logs reduced titer compared with
      rMERS-CoV. Northern blot analyses confirmed the associated molecular changes in
      the recombinant viruses, and sequence analysis demonstrated that RFP was
      expressed from the appropriate consensus sequence AACGAA. We further show
      dipeptidyl peptidase 4 expression, MERS-CoV replication, and RNA and protein
      synthesis in human airway epithelial cell cultures, primary lung fibroblasts,
      primary lung microvascular endothelial cells, and primary alveolar type II
      pneumocytes, demonstrating a much broader tissue tropism than severe acute
      respiratory syndrome coronavirus. The availability of a MERS-CoV molecular clone,
      as well as recombinant viruses expressing indicator proteins, will allow for high
      throughput testing of therapeutic compounds and provide a genetic platform for
      studying gene function and the rational design of live virus vaccines.

PMID- 24043792
TI  - TLR-induced PAI-2 expression suppresses IL-1beta processing via increasing
      autophagy and NLRP3 degradation.
AB  - The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, a
      multiprotein complex, triggers caspase-1 activation and maturation of the
      proinflammatory cytokines IL-1beta and IL-18 upon sensing a wide range of
      pathogen- and damage-associated molecules. Dysregulation of NLRP3 inflammasome
      activity contributes to the pathogenesis of many diseases, but its regulation
      remains poorly defined. Here we show that depletion of plasminogen activator
      inhibitor type 2 (PAI-2), a serine protease inhibitor, resulted in NLRP3- and ASC
      (apoptosis-associated Speck-like protein containing a C-terminal caspase
      recruitment domain)-dependent caspase-1 activation and IL-1beta secretion in
      macrophages upon Toll-like receptor 2 (TLR2) and TLR4 engagement. TLR2 or TLR4
      agonist induced PAI-2 expression, which subsequently stabilized the autophagic
      protein Beclin 1 to promote autophagy, resulting in decreases in mitochondrial
      reactive oxygen species, NLRP3 protein level, and pro-IL-1beta processing.
      Likewise, overexpressing Beclin 1 in PAI-2-deficient cells rescued the
      suppression of NLRP3 activation in response to LPS. Together, our data identify a
      tier of TLR signaling in controlling NLRP3 inflammasome activation and reveal a
      cell-autonomous mechanism which inversely regulates TLR- or Escherichia coli
      induced mitochondrial dysfunction, oxidative stress, and IL-1beta-driven
      inflammation. 

PMID- 24043793
TI  - Molecular decision trees realized by ultrafast electronic spectroscopy.
AB  - The outcome of a light-matter interaction depends on both the state of matter and
      the state of light. It is thus a natural setting for implementing bilinear
      classical logic. A description of the state of a time-varying system requires
      measuring an (ideally complete) set of time-dependent observables. Typically,
      this is prohibitive, but in weak-field spectroscopy we can move toward this goal
      because only a finite number of levels are accessible. Recent progress in
      nonlinear spectroscopies means that nontrivial measurements can be implemented
      and thereby give rise to interesting logic schemes where the outputs are
      functions of the observables. Lie algebra offers a natural tool for generating
      the outcome of the bilinear light-matter interaction. We show how to synthesize
      these ideas by explicitly discussing three-photon spectroscopy of a
      bichromophoric molecule for which there are four accessible states. Switching
      logic would use the on-off occupancies of these four states as outcomes. Here, we
      explore the use of all 16 observables that define the time-evolving state of the
      bichromophoric system. The bilinear laser-system interaction with the three
      pulses of the setup of a 2D photon echo spectroscopy experiment can be used to
      generate a rich parallel logic that corresponds to the implementation of a
      molecular decision tree. Our simulations allow relaxation by weak coupling to the
      environment, which adds to the complexity of the logic operations. 

PMID- 24043794
TI  - Urocortin 2 autocrine/paracrine and pharmacologic effects to activate AMP
      activated protein kinase in the heart.
AB  - Urocortin 2 (Ucn2), a peptide of the corticotropin-releasing factor (CRF) family,
      binds with high affinity to type 2 CRF receptors (CRFR2) on cardiomyocytes and
      confers protection against ischemia/reperfusion. The mechanisms by which the Ucn2
      CRFR2 axis mitigates against ischemia/reperfusion injury remain incompletely
      delineated. Activation of AMP-activated protein kinase (AMPK) also limits cardiac
      damage during ischemia/reperfusion. AMPK is classically activated by alterations
      in cellular energetics; however, hormones, cytokines, and additional
      autocrine/paracrine factors also modulate its activity. We examined the effects
      of both the endogenous cardiac Ucn2 autocrine/paracrine pathway and Ucn2
      treatment on AMPK regulation. Ucn2 treatment increased AMPK activation and
      downstream acetyl-CoA carboxylase phosphorylation and glucose uptake in isolated
      heart muscles. These actions were blocked by the CRFR2 antagonist anti-sauvagine
      30 and by a PKCepsilon translocation-inhibitor peptide (epsilonV1-2). Hypoxia
      induced AMPK activation was also blunted in heart muscles by preincubation with
      either anti-sauvagine-30, a neutralizing anti-Ucn2 antibody, or epsilonV1-2.
      Treatment with Ucn2 in vivo augmented ischemic AMPK activation and reduced
      myocardial injury and cardiac contractile dysfunction after regional
      ischemia/reperfusion in mice. Ucn2 also directly activated AMPK in ex vivo
      perfused mouse hearts and diminished injury and contractile dysfunction during
      ischemia/reperfusion. Thus, both Ucn2 treatment and the endogenous cardiac Ucn2
      autocrine/paracrine pathway activate AMPK signaling pathway, via a PKCepsilon
      dependent mechanism, defining a Ucn2-CRFR2-PKCepsilon-AMPK pathway that mitigates
      against ischemia/reperfusion injury. 

PMID- 24043795
TI  - Isotropic band gaps and freeform waveguides observed in hyperuniform disordered
      photonic solids.
AB  - Recently, disordered photonic media and random textured surfaces have attracted
      increasing attention as strong light diffusers with broadband and wide-angle
      properties. We report the experimental realization of an isotropic complete
      photonic band gap (PBG) in a 2D disordered dielectric structure. This structure
      is designed by a constrained optimization method, which combines advantages of
      both isotropy due to disorder and controlled scattering properties due to low
      density fluctuations (hyperuniformity) and uniform local topology. Our
      experiments use a modular design composed of Al2O3 walls and cylinders arranged
      in a hyperuniform disordered network. We observe a complete PBG in the microwave
      region, in good agreement with theoretical simulations, and show that the
      intrinsic isotropy of this unique class of PBG materials enables remarkable
      design freedom, including the realization of waveguides with arbitrary bending
      angles impossible in photonic crystals. This experimental verification of a
      complete PBG and realization of functional defects in this unique class of
      materials demonstrate their potential as building blocks for precise manipulation
      of photons in planar optical microcircuits and has implications for disordered
      acoustic and electronic band gap materials. 

PMID- 24043796
TI  - Fe-N2/CO complexes that model a possible role for the interstitial C atom of FeMo
      cofactor (FeMoco).
AB  - We report here a series of four- and five-coordinate Fe model complexes that
      feature an axial tri(silyl)methyl ligand positioned trans to a substrate-binding
      site. This arrangement is used to crudely model a single-belt Fe site of the FeMo
      cofactor that might bind N2 at a position trans to the interstitial C atom.
      Reduction of a trigonal pyramidal Fe(I) complex leads to uptake of N2 and
      subsequent functionalization furnishes an open-shell Fe-diazenido complex. A
      related series of five-coordinate Fe-CO complexes stable across three redox
      states is also described. Spectroscopic, crystallographic, and Density Functional
      Theory (DFT) studies of these complexes suggest that a decrease in the covalency
      of the Fe-C(alkyl) interaction occurs upon reduction and substrate binding. This
      leads to unusually long Fe-C(alkyl) bond distances that reflect an ionic Fe-C
      bond. The data presented are contextualized in support of a hypothesis wherein
      modulation of a belt Fe-C interaction in the FeMo-cofactor facilitates substrate
      binding and reduction.

PMID- 24043797
TI  - Early evolution of the T-box transcription factor family.
AB  - Developmental transcription factors are key players in animal multicellularity,
      being members of the T-box family that are among the most important. Until
      recently, T-box transcription factors were thought to be exclusively present in
      metazoans. Here, we report the presence of T-box genes in several nonmetazoan
      lineages, including ichthyosporeans, filastereans, and fungi. Our data confirm
      that Brachyury is the most ancient member of the T-box family and establish that
      the T-box family diversified at the onset of Metazoa. Moreover, we demonstrate
      functional conservation of a homolog of Brachyury of the protist Capsaspora
      owczarzaki in Xenopus laevis. By comparing the molecular phenotype of C.
      owczarzaki Brachyury with that of homologs of early branching metazoans, we
      define a clear difference between unicellular holozoan and metazoan Brachyury
      homologs, suggesting that the specificity of Brachyury emerged at the origin of
      Metazoa. Experimental determination of the binding preferences of the C.
      owczarzaki Brachyury results in a similar motif to that of metazoan Brachyury and
      other T-box classes. This finding suggests that functional specificity between
      different T-box classes is likely achieved by interaction with alternative
      cofactors, as opposed to differences in binding specificity. 

PMID- 24043798
TI  - A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic
      transcriptional machinery.
AB  - Circadian clocks in mammals are built on a negative feedback loop in which the
      heterodimeric transcription factor circadian locomotor output cycles kaput
      (CLOCK)-brain, muscle Arnt-like 1 (BMAL1) drives the expression of its own
      inhibitors, the PERIOD and CRYPTOCHROME proteins. Reactivation of CLOCK-BMAL1
      occurs at a specific time several hours after PERIOD and CRYPTOCHROME protein
      turnover, but the mechanism underlying this process is unknown. We found that
      mouse BMAL1 complexes include TRAP150 (thyroid hormone receptor-associated
      protein-150; also known as THRAP3). TRAP150 is a selective coactivator for CLOCK
      BMAL1, which oscillates under CLOCK-BMAL1 transcriptional control. TRAP150
      promotes CLOCK-BMAL1 binding to target genes and links CLOCK-BMAL1 to the
      transcriptional machinery at target-gene promoters. Depletion of TRAP150 caused
      low-amplitude, long-period rhythms, identifying it as a positive clock element.
      The activity of TRAP150 defines a positive feedback loop within the clock and
      provides a potential mechanism for timing the reactivation of circadian
      transcription. 

PMID- 24043799
TI  - ABI3 controls embryo degreening through Mendel's I locus.
AB  - Chlorophyll (chl) is essential for light capture and is the starting point that
      provides the energy for photosynthesis and thus plant growth. Obviously, for this
      reason, retention of the green chlorophyll pigment is considered a desirable crop
      trait. However, the presence of chlorophyll in mature seeds can be an undesirable
      trait that can affect seed maturation, seed oil quality, and meal quality.
      Occurrence of mature green seeds in oil crops such as canola and soybean due to
      unfavorable weather conditions during seed maturity is known to cause severe
      losses in revenue. One recently identified candidate that controls the
      chlorophyll degradation machinery is the stay-green gene, SGR1 that was mapped to
      Mendel's I locus responsible for cotyledon color (yellow versus green) in peas. A
      defect in SGR1 leads to leaf stay-green phenotypes in Arabidopsis and rice, but
      the role of SGR1 in seed degreening and the signaling machinery that converges on
      SGR1 have remained elusive. To decipher the gene regulatory network that controls
      degreening in Arabidopsis, we have used an embryo stay-green mutant to
      demonstrate that embryo degreening is achieved by the SGR family and that this
      whole process is regulated by the phytohormone abscisic acid (ABA) through
      ABSCISIC ACID INSENSITIVE 3 (ABI3); a B3 domain transcription factor that has a
      highly conserved and essential role in seed maturation, conferring desiccation
      tolerance. Misexpression of ABI3 was sufficient to rescue cold-induced green seed
      phenotype in Arabidopsis. This finding reveals a mechanistic role for ABI3 during
      seed degreening and thus targeting of this pathway could provide a solution to
      the green seed problem in various oil-seed crops. 

PMID- 24043800
TI  - Microbial battery for efficient energy recovery.
AB  - By harnessing the oxidative power of microorganisms, energy can be recovered from
      reservoirs of less-concentrated organic matter, such as marine sediment,
      wastewater, and waste biomass. Left unmanaged, these reservoirs can become
      eutrophic dead zones and sites of greenhouse gas generation. Here, we introduce a
      unique means of energy recovery from these reservoirs-a microbial battery (MB)
      consisting of an anode colonized by microorganisms and a reoxidizable solid-state
      cathode. The MB has a single-chamber configuration and does not contain ion
      exchange membranes. Bench-scale MB prototypes were constructed from commercially
      available materials using glucose or domestic wastewater as electron donor and
      silver oxide as a coupled solid-state oxidant electrode. The MB achieved an
      efficiency of electrical energy conversion of 49% based on the combustion
      enthalpy of the organic matter consumed or 44% based on the organic matter added.
      Electrochemical reoxidation of the solid-state electrode decreased net efficiency
      to about 30%. This net efficiency of energy recovery (unoptimized) is comparable
      to methane fermentation with combined heat and power. 

PMID- 24043801
TI  - HIV-1 suppression and durable control by combining single broadly neutralizing
      antibodies and antiretroviral drugs in humanized mice.
AB  - Effective control of HIV-1 infection in humans is achieved using combinations of
      antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of
      viremia can be achieved using either ART or by immunotherapy using combinations
      of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1
      infected hu-mice with a combination of three highly potent bNAbs not only
      resulted in complete viremic control but also led to a reduction in cell
      associated HIV-1 DNA. Moreover, lowering the initial viral load by
      coadministration of ART and immunotherapy enabled prolonged viremic control by a
      single bNAb after ART was withdrawn. Similarly, a single injection of adeno
      associated virus directing expression of one bNAb produced durable viremic
      control after ART was terminated. We conclude that immunotherapy reduces plasma
      viral load and cell-associated HIV-1 DNA and that decreasing the initial viral
      load enables single bNAbs to control viremia in hu-mice. 

PMID- 24043802
TI  - C-terminal processing of reaction center protein D1 is essential for the function
      and assembly of photosystem II in Arabidopsis.
AB  - Photosystem II (PSII) reaction center protein D1 is synthesized as a precursor
      (pD1) with a short C-terminal extension. The pD1 is processed to mature D1 by
      carboxyl-terminal peptidase A to remove the C-terminal extension and form active
      protein. Here we report functional characterization of the Arabidopsis gene
      encoding D1 C-terminal processing enzyme (AtCtpA) in the chloroplast thylakoid
      lumen. Recombinant AtCtpA converted pD1 to mature D1 and a mutant lacking AtCtpA
      retained all D1 in precursor form, confirming that AtCtpA is solely responsible
      for processing. As with cyanobacterial ctpa, a knockout Arabidopsis atctpa mutant
      was lethal under normal growth conditions but was viable with sucrose under low
      light conditions. Viable plants, however, showed deficiencies in PSII and
      thylakoid stacking. Surprisingly, unlike its cyanobacterial counterpart, the
      Arabidopsis mutant retained both monomer and dimer forms of the PSII complexes
      that, although nonfunctional, contained both the core and extrinsic subunits.
      This mutant was also essentially devoid of PSII supercomplexes, providing an
      unexpected link between D1 maturation and supercomplex assembly. A knock-down
      mutant expressing about 2% wild-type level of AtCtpA showed normal growth under
      low light but was stunted and accumulated pD1 under high light, indicative of
      delayed C-terminal processing. Although demonstrating the functional significance
      of C-terminal D1 processing in PSII biogenesis, our study reveals an unsuspected
      link between D1 maturation and PSII supercomplex assembly in land plants, opening
      an avenue for exploring the mechanism for the association of light-harvesting
      complexes with the PSII core complexes. 

PMID- 24043803
TI  - Predicting the public health benefit of vaccinating cattle against Escherichia
      coli O157.
AB  - Identifying the major sources of risk in disease transmission is key to designing
      effective controls. However, understanding of transmission dynamics across
      species boundaries is typically poor, making the design and evaluation of
      controls particularly challenging for zoonotic pathogens. One such global
      pathogen is Escherichia coli O157, which causes a serious and sometimes fatal
      gastrointestinal illness. Cattle are the main reservoir for E. coli O157, and
      vaccines for cattle now exist. However, adoption of vaccines is being delayed by
      conflicting responsibilities of veterinary and public health agencies, economic
      drivers, and because clinical trials cannot easily test interventions across
      species boundaries, lack of information on the public health benefits. Here, we
      examine transmission risk across the cattle-human species boundary and show three
      key results. First, supershedding of the pathogen by cattle is associated with
      the genetic marker stx2. Second, by quantifying the link between shedding density
      in cattle and human risk, we show that only the relatively rare supershedding
      events contribute significantly to human risk. Third, we show that this finding
      has profound consequences for the public health benefits of the cattle vaccine. A
      naive evaluation based on efficacy in cattle would suggest a 50% reduction in
      risk; however, because the vaccine targets the major source of human risk, we
      predict a reduction in human cases of nearly 85%. By accounting for
      nonlinearities in transmission across the human-animal interface, we show that
      adoption of these vaccines by the livestock industry could prevent substantial
      numbers of human E. coli O157 cases. 

PMID- 24043804
TI  - Measurements of methane emissions at natural gas production sites in the United
      States.
AB  - Engineering estimates of methane emissions from natural gas production have led
      to varied projections of national emissions. This work reports direct
      measurements of methane emissions at 190 onshore natural gas sites in the United
      States (150 production sites, 27 well completion flowbacks, 9 well unloadings,
      and 4 workovers). For well completion flowbacks, which clear fractured wells of
      liquid to allow gas production, methane emissions ranged from 0.01 Mg to 17 Mg
      (mean = 1.7 Mg; 95% confidence bounds of 0.67-3.3 Mg), compared with an average
      of 81 Mg per event in the 2011 EPA national emission inventory from April 2013.
      Emission factors for pneumatic pumps and controllers as well as equipment leaks
      were both comparable to and higher than estimates in the national inventory.
      Overall, if emission factors from this work for completion flowbacks, equipment
      leaks, and pneumatic pumps and controllers are assumed to be representative of
      national populations and are used to estimate national emissions, total annual
      emissions from these source categories are calculated to be 957 Gg of methane
      (with sampling and measurement uncertainties estimated at +/- 200 Gg). The
      estimate for comparable source categories in the EPA national inventory is ~1,200
      Gg. Additional measurements of unloadings and workovers are needed to produce
      national emission estimates for these source categories. The 957 Gg in emissions
      for completion flowbacks, pneumatics, and equipment leaks, coupled with EPA
      national inventory estimates for other categories, leads to an estimated 2,300 Gg
      of methane emissions from natural gas production (0.42% of gross gas production).

PMID- 24043805
TI  - Spatiotemporal dynamics in understanding hand-object interactions.
AB  - It is generally accepted that visual perception results from the activation of a
      feed-forward hierarchy of areas, leading to increasingly complex representations.
      Here we present evidence for a fundamental role of backward projections to the
      occipito-temporal region for understanding conceptual object properties. The
      evidence is based on two studies. In the first study, using high-density EEG, we
      showed that during the observation of how objects are used there is an early
      activation of occipital and temporal areas, subsequently reaching the pole of the
      temporal lobe, and a late reactivation of the visual areas. In the second study,
      using transcranial magnetic stimulation over the occipital lobe, we showed a
      clear impairment in the accuracy of recognition of how objects are used during
      both early activation and, most importantly, late occipital reactivation. These
      findings represent strong neurophysiological evidence that a top-down mechanism
      is fundamental for understanding conceptual object properties, and suggest that a
      similar mechanism might be also present for other higher-order cognitive
      functions. 

PMID- 24043806
TI  - Wnt signaling potentiates nevogenesis.
AB  - Cellular senescence is a stable proliferation arrest associated with an altered
      secretory pathway (senescence-associated secretory phenotype). Cellular
      senescence is also a tumor suppressor mechanism, to which both proliferation
      arrest and senescence-associated secretory phenotype are thought to contribute.
      The melanocytes within benign human nevi are a paradigm for tumor-suppressive
      senescent cells in a premalignant neoplasm. Here a comparison of proliferating
      and senescent melanocytes and melanoma cell lines by RNA sequencing emphasizes
      the importance of senescence-associated proliferation arrest in suppression of
      transformation. Previous studies showed that activation of the Wnt signaling
      pathway can delay or bypass senescence. Consistent with this, we present evidence
      that repression of Wnt signaling contributes to melanocyte senescence in vitro.
      Surprisingly, Wnt signaling is active in many senescent human melanocytes in
      nevi, and this is linked to histological indicators of higher proliferative and
      malignant potential. In a mouse, activated Wnt signaling delays senescence
      associated proliferation arrest to expand the population of senescent oncogene
      expressing melanocytes. These results suggest that Wnt signaling can potentiate
      nevogenesis in vivo by delaying senescence. Further, we suggest that activated
      Wnt signaling in human nevi undermines senescence-mediated tumor suppression and
      enhances the probability of malignancy. 

PMID- 24043807
TI  - A gating mechanism of pentameric ligand-gated ion channels.
AB  - Pentameric ligand-gated ion channels (pLGICs) play a central role in
      intercellular communication in the nervous system and are involved in fundamental
      processes such as attention, learning, and memory. They are oligomeric protein
      assemblies that convert a chemical signal into an ion flux through the
      postsynaptic membrane, but the molecular mechanism of gating ions has remained
      elusive. Here, we present atomistic molecular dynamics simulations of the
      prokaryotic channels from Gloeobacter violaceus (GLIC) and Erwinia chrysanthemi
      (ELIC), whose crystal structures are thought to represent the active and the
      resting states of pLGICs, respectively, and of the eukaryotic glutamate-gated
      chloride channel from Caenorhabditis elegans (GluCl), whose open-channel
      structure was determined complexed with the positive allosteric modulator
      ivermectin. Structural observables extracted from the trajectories of GLIC and
      ELIC are used as progress variables to analyze the time evolution of GluCl, which
      was simulated in the absence of ivermectin starting from the structure with bound
      ivermectin. The trajectory of GluCl with ivermectin removed shows a sequence of
      structural events that couple agonist unbinding from the extracellular domain to
      ion-pore closing in the transmembrane domain. Based on these results, we propose
      a structural mechanism for the allosteric communication leading to
      deactivation/activation of the GluCl channel. This model of gating emphasizes the
      coupling between the quaternary twisting and the opening/closing of the ion pore
      and is likely to apply to other members of the pLGIC family. 

PMID- 24043808
TI  - Enhanced group II intron retrohoming in magnesium-deficient Escherichia coli via
      selection of mutations in the ribozyme core.
AB  - Mobile group II introns are bacterial retrotransposons thought to be evolutionary
      ancestors of spliceosomal introns and retroelements in eukaryotes. They consist
      of a catalytically active intron RNA ("ribozyme") and an intron-encoded reverse
      transcriptase, which function together to promote RNA splicing and intron
      mobility via reverse splicing of the intron RNA into new DNA sites
      ("retrohoming"). Although group II introns are active in bacteria, their natural
      hosts, they function inefficiently in eukaryotes, where lower free Mg(2+)
      concentrations decrease their ribozyme activity and constitute a natural barrier
      to group II intron proliferation within nuclear genomes. Here, we show that
      retrohoming of the Ll.LtrB group II intron is strongly inhibited in an
      Escherichia coli mutant lacking the Mg(2+) transporter MgtA, and we use this
      system to select mutations in catalytic core domain V (DV) that partially rescue
      retrohoming at low Mg(2+) concentrations. We thus identified mutations in the
      distal stem of DV that increase retrohoming efficiency in the MgtA mutant up to
      22-fold. Biochemical assays of splicing and reverse splicing indicate that the
      mutations increase the fraction of intron RNA that folds into an active
      conformation at low Mg(2+) concentrations, and terbium-cleavage assays suggest
      that this increase is due to enhanced Mg(2+) binding to the distal stem of DV.
      Our findings indicate that DV is involved in a critical Mg(2+)-dependent RNA
      folding step in group II introns and demonstrate the feasibility of selecting
      intron variants that function more efficiently at low Mg(2+) concentrations, with
      implications for evolution and potential applications in gene targeting. 

PMID- 24043809
TI  - Reactivation of stalled polyribosomes in synaptic plasticity.
AB  - Some forms of synaptic plasticity require rapid, local activation of protein
      synthesis. Although this is thought to reflect recruitment of mRNAs to free
      ribosomes, this would limit the speed and magnitude of translational activation.
      Here we provide compelling in situ evidence supporting an alternative model in
      which synaptic mRNAs are transported as stably paused polyribosomes. Remarkably,
      we show that metabotropic glutamate receptor activation allows the synthesis of
      proteins that lead to a functional long-term depression phenotype even when
      translation initiation has been greatly reduced. Thus, neurons evolved a unique
      mechanism to swiftly translate synaptic mRNAs into functional protein upon
      synaptic signaling using stalled polyribosomes to bypass the rate-limiting step
      of translation initiation. Because dysregulated plasticity is implicated in
      neurodevelopmental and psychiatric disorders such as fragile X syndrome, this
      work uncovers a unique translational target for therapies. 

PMID- 24043810
TI  - Predicting overfishing and extinction threats in multispecies fisheries.
AB  - Threats to species from commercial fishing are rarely identified until species
      have suffered large population declines, by which time remedial actions can have
      severe economic consequences, such as closure of fisheries. Many of the species
      most threatened by fishing are caught in multispecies fisheries, which can remain
      profitable even as populations of some species collapse. Here we show for
      multispecies fisheries that the biological and socioeconomic conditions that
      would eventually cause species to be severely depleted or even driven extinct can
      be identified decades before those species experience high harvest rates or
      marked population declines. Because fishing effort imposes a common source of
      mortality on all species in a fishery, the long-term impact of a fishery on a
      species is predicted by measuring its loss rate relative to that of species that
      influence the fishery's maximal effort. We tested our approach on eight Pacific
      tuna and billfish populations, four of which have been identified recently as in
      decline and threatened with overfishing. The severe depletion of all four
      populations could have been predicted in the 1950s, using our approach. Our
      results demonstrate that species threatened by human harvesting can be identified
      much earlier, providing time for adjustments in harvesting practices before
      consequences become severe and fishery closures or other socioeconomically
      disruptive interventions are required to protect species. 

PMID- 24043811
TI  - Observation of the controlled assembly of preclick components in the in situ
      click chemistry generation of a chitinase inhibitor.
AB  - The Huisgen cycloaddition of azides and alkynes, accelerated by target
      biomolecules, termed "in situ click chemistry," has been successfully exploited
      to discover highly potent enzyme inhibitors. We have previously reported a
      specific Serratia marcescens chitinase B (SmChiB)-templated syn-triazole
      inhibitor generated in situ from an azide-bearing inhibitor and an alkyne
      fragment. Several in situ click chemistry studies have been reported. Although
      some mechanistic evidence has been obtained, such as X-ray analysis of [protein]
      ["click ligand"] complexes, indicating that proteins act as both mold and
      template between unique pairs of azide and alkyne fragments, to date,
      observations have been based solely on "postclick" structural information. Here,
      we describe crystal structures of SmChiB complexed with an azide ligand and an O
      allyl oxime fragment as a mimic of a click partner, revealing a mechanism for
      accelerating syn-triazole formation, which allows generation of its own distinct
      inhibitor. We have also performed density functional theory calculations based on
      the X-ray structure to explore the acceleration of the Huisgen cycloaddition by
      SmChiB. The density functional theory calculations reasonably support that SmChiB
      plays a role by the cage effect during the pretranslation and posttranslation
      states of selective syn-triazole click formation. 

PMID- 24043812
TI  - Intravaginal ring eluting tenofovir disoproxil fumarate completely protects
      macaques from multiple vaginal simian-HIV challenges.
AB  - Topical preexposure prophylaxis interrupts HIV transmission at the site of
      mucosal exposure. Intermittently dosed vaginal gels containing the HIV-1 reverse
      transcriptase inhibitor tenofovir protected pigtailed macaques depending on the
      timing of viral challenge relative to gel application. However, modest or no
      protection was observed in clinical trials. Intravaginal rings (IVRs) may improve
      efficacy by providing long-term sustained drug delivery leading to constant
      mucosal antiretroviral concentrations and enhancing adherence. Although a few
      IVRs have entered the clinical pipeline, 100% efficacy in a repeated macaque
      vaginal challenge model has not been achieved. Here we describe a reservoir IVR
      technology that delivers the tenofovir prodrug tenofovir disoproxil fumarate
      (TDF) continuously over 28 d. With four monthly ring changes in this repeated
      challenge model, TDF IVRs generated reproducible and protective drug levels. All
      TDF IVR-treated macaques (n = 6) remained seronegative and simian-HIV RNA
      negative after 16 weekly vaginal exposures to 50 tissue culture infectious dose
      SHIV162p3. In contrast, 11/12 control macaques became infected, with a median of
      four exposures assuming an eclipse of 7 d from infection to virus RNA detection.
      Protection was associated with tenofovir levels in vaginal fluid [mean 1.8 *
      10(5) ng/mL (range 1.1 * 10(4) to 6.6 * 10(5) ng/mL)] and ex vivo antiviral
      activity of cervicovaginal lavage samples. These observations support further
      advancement of TDF IVRs as well as the concept that extended duration drug
      delivery devices delivering topical antiretrovirals could be effective tools in
      preventing the sexual transmission of HIV in humans. 

PMID- 24043813
TI  - Structural basis for discriminatory recognition of Plasmodium lactate
      dehydrogenase by a DNA aptamer.
AB  - DNA aptamers have significant potential as diagnostic and therapeutic agents, but
      the paucity of DNA aptamer-target structures limits understanding of their
      molecular binding mechanisms. Here, we report a distorted hairpin structure of a
      DNA aptamer in complex with an important diagnostic target for malaria:
      Plasmodium falciparum lactate dehydrogenase (PfLDH). Aptamers selected from a DNA
      library were highly specific and discriminatory for Plasmodium as opposed to
      human lactate dehydrogenase because of a counterselection strategy used during
      selection. Isothermal titration calorimetry revealed aptamer binding to PfLDH
      with a dissociation constant of 42 nM and 2:1 protein:aptamer molar
      stoichiometry. Dissociation constants derived from electrophoretic mobility shift
      assays and surface plasmon resonance experiments were consistent. The
      aptamer:protein complex crystal structure was solved at 2.1-A resolution,
      revealing two aptamers bind per PfLDH tetramer. The aptamers showed a unique
      distorted hairpin structure in complex with PfLDH, displaying a Watson-Crick base
      paired stem together with two distinct loops each with one base flipped out by
      specific interactions with PfLDH. Aptamer binding specificity is dictated by
      extensive interactions of one of the aptamer loops with a PfLDH loop that is
      absent in human lactate dehydrogenase. We conjugated the aptamer to gold
      nanoparticles and demonstrated specificity of colorimetric detection of PfLDH
      over human lactate dehydrogenase. This unique distorted hairpin aptamer complex
      provides a perspective on aptamer-mediated molecular recognition and may guide
      rational design of better aptamers for malaria diagnostics. 

PMID- 24043814
TI  - Blue whale earplug reveals lifetime contaminant exposure and hormone profiles.
AB  - Lifetime contaminant and hormonal profiles have been reconstructed for an
      individual male blue whale (Balaenoptera musculus, Linnaeus 1758) using the
      earplug as a natural aging matrix that is also capable of archiving and
      preserving lipophilic compounds. These unprecedented lifetime profiles (i.e.,
      birth to death) were reconstructed with a 6-mo resolution for a wide range of
      analytes including cortisol (stress hormone), testosterone (developmental
      hormone), organic contaminants (e.g., pesticides and flame retardants), and
      mercury. Cortisol lifetime profiles revealed a doubling of cortisol levels over
      baseline. Testosterone profiles suggest this male blue whale reached sexual
      maturity at approximately 10 y of age, which corresponds well with and improves
      on previous estimates. Early periods of the reconstructed contaminant profiles
      for pesticides (such as dichlorodiphenyltrichloroethanes and chlordanes),
      polychlorinated biphenyls, and polybrominated diphenyl ethers demonstrate
      significant maternal transfer occurred at 0-12 mo. The total lifetime organic
      contaminant burden measured between the earplug (sum of contaminants in laminae
      layers) and blubber samples from the same organism were similar. Total mercury
      profiles revealed reduced maternal transfer and two distinct pulse events
      compared with organic contaminants. The use of a whale earplug to reconstruct
      lifetime chemical profiles will allow for a more comprehensive examination of
      stress, development, and contaminant exposure, as well as improve the assessment
      of contaminant use/emission, environmental noise, ship traffic, and climate
      change on these important marine sentinels. 

PMID- 24043815
TI  - Endothelin-2 signaling in the neural retina promotes the endothelial tip cell
      state and inhibits angiogenesis.
AB  - Endothelin signaling is required for neural crest migration and homeostatic
      regulation of blood pressure. Here, we report that constitutive overexpression of
      Endothelin-2 (Edn2) in the mouse retina perturbs vascular development by
      inhibiting endothelial cell migration across the retinal surface and subsequent
      endothelial cell invasion into the retina. Developing endothelial cells exist in
      one of two states: tip cells at the growing front and stalk cells in the vascular
      plexus behind the front. This division of endothelial cell states is one of the
      central organizing principles of angiogenesis. In the developing retina, Edn2
      overexpression leads to overproduction of endothelial tip cells by both
      morphologic and molecular criteria. Spatially localized overexpression of Edn2
      produces a correspondingly localized endothelial response. Edn2 overexpression in
      the early embryo inhibits vascular development at midgestation, but Edn2
      overexpression in developing skin and brain has no discernible effect on vascular
      structure. Inhibition of retinal angiogenesis by Edn2 requires expression of
      Endothelin receptor A but not Endothelin receptor B in the neural retina. Taken
      together, these observations imply that the neural retina responds to Edn2 by
      synthesizing one or more factors that promote the endothelial tip cell state and
      inhibit angiogenesis. The response to Edn2 is sufficiently potent that it
      overrides the activities of other homeostatic regulators of angiogenesis, such as
      Vegf. 

PMID- 24043816
TI  - Transcription factor ZBED6 affects gene expression, proliferation, and cell death
      in pancreatic beta cells.
AB  - We have investigated whether the recently discovered transcription factor, zinc
      finger BED domain-containing protein 6 (ZBED6), is expressed in insulin-producing
      cells and, if so, to what extent it affects beta cell function. ZBED6 was
      translated from a ZC3H11A transcript in which the ZBED6-containing intron was
      retained. ZBED6 was present in mouse betaTC-6 cells and human islets as a double
      nuclear band at 115/120 kDa and as a single cytoplasmic band at 95-100 kDa, which
      lacked N-terminal nuclear localization signals. We propose that ZBED6 supports
      proliferation and survival of beta cells, possibly at the expense of specialized
      beta cell function-i.e., insulin production-because (i) the nuclear ZBED6 were
      the predominant forms in rapidly proliferating betaTC-6 cells, but not in human
      islet cells; (ii) down-regulation of ZBED6 in betaTC-6 cells resulted in altered
      morphology, decreased proliferation, a partial S/G2 cell-cycle arrest, increased
      expression of beta cell-specific genes, and higher rates of apoptosis; (iii)
      silencing of ZBED6 in the human PANC-1 duct cell line reduced proliferation
      rates; and (iv) ZBED6 binding was preferentially to genes that control
      transcription, macromolecule biosynthesis, and apoptosis. Furthermore, it is
      possible that beta cells, by switching from full length to a truncated form of
      ZBED6, can decide the subcellular localization of ZBED6, thereby achieving
      differential ZBED6-mediated transcriptional regulation. 

PMID- 24043817
TI  - DNA cloning: a personal view after 40 years.
AB  - In November 1973, my colleagues A. C. Y. Chang, H. W. Boyer, R. B. Helling, and I
      reported in PNAS that individual genes can be cloned and isolated by
      enzymatically cleaving DNA molecules into fragments, linking the fragments to an
      autonomously replicating plasmid, and introducing the resulting recombinant DNA
      molecules into bacteria. A few months later, Chang and I reported that genes from
      unrelated bacterial species can be combined and propagated using the same
      approach and that interspecies recombinant DNA molecules can produce a
      biologically functional protein in a foreign host. Soon afterward, Boyer's
      laboratory and mine published our collaborative discovery that even genes from
      animal cells can be cloned in bacteria. These three PNAS papers quickly led to
      the use of DNA cloning methods in multiple areas of the biological and chemical
      sciences. They also resulted in a highly public controversy about the potential
      hazards of laboratory manipulation of genetic material, a decision by Stanford
      University and the University of California to seek patents on the technology
      that Boyer and I had invented, and the application of DNA cloning methods for
      commercial purposes. In the 40 years that have passed since publication of our
      findings, use of DNA cloning has produced insights about the workings of genes
      and cells in health and disease and has altered the nature of the biotechnology
      and biopharmaceutical industries. Here, I provide a personal perspective of the
      events that led to, and followed, our report of DNA cloning. 

PMID- 24043818
TI  - Bats carry pathogenic hepadnaviruses antigenically related to hepatitis B virus
      and capable of infecting human hepatocytes.
AB  - The hepatitis B virus (HBV), family Hepadnaviridae, is one of most relevant human
      pathogens. HBV origins are enigmatic, and no zoonotic reservoirs are known. Here,
      we screened 3,080 specimens from 54 bat species representing 11 bat families for
      hepadnaviral DNA. Ten specimens (0.3%) from Panama and Gabon yielded unique
      hepadnaviruses in coancestral relation to HBV. Full genome sequencing allowed
      classification as three putative orthohepadnavirus species based on genome
      lengths (3,149-3,377 nt), presence of middle HBV surface and X-protein genes, and
      sequence distance criteria. Hepatic tropism in bats was shown by quantitative PCR
      and in situ hybridization. Infected livers showed histopathologic changes
      compatible with hepatitis. Human hepatocytes transfected with all three bat
      viruses cross-reacted with sera against the HBV core protein, concordant with the
      phylogenetic relatedness of these hepadnaviruses and HBV. One virus from Uroderma
      bilobatum, the tent-making bat, cross-reacted with monoclonal antibodies against
      the HBV antigenicity determining S domain. Up to 18.4% of bat sera contained
      antibodies against bat hepadnaviruses. Infectious clones were generated to study
      all three viruses in detail. Hepatitis D virus particles pseudotyped with surface
      proteins of U. bilobatum HBV, but neither of the other two viruses could infect
      primary human and Tupaia belangeri hepatocytes. Hepatocyte infection occurred
      through the human HBV receptor sodium taurocholate cotransporting polypeptide but
      could not be neutralized by sera from vaccinated humans. Antihepadnaviral
      treatment using an approved reverse transcriptase inhibitor blocked replication
      of all bat hepadnaviruses. Our data suggest that bats may have been ancestral
      sources of primate hepadnaviruses. The observed zoonotic potential might affect
      concepts aimed at eradicating HBV. 

PMID- 24043819
TI  - 2,4,6-trichloroanisole is a potent suppressor of olfactory signal transduction.
AB  - We investigated the sensitivity of single olfactory receptor cells to 2,4,6
      trichloroanisole (TCA), a compound known for causing cork taint in wines. Such
      off-flavors have been thought to originate from unpleasant odor qualities evoked
      by contaminants. However, we here show that TCA attenuates olfactory transduction
      by suppressing cyclic nucleotide-gated channels, without evoking odorant
      responses. Surprisingly, suppression was observed even at extremely low (i.e.,
      attomolar) TCA concentrations. The high sensitivity to TCA was associated with
      temporal integration of the suppression effect. We confirmed that potent
      suppression by TCA and similar compounds was correlated with their lipophilicity,
      as quantified by the partition coefficient at octanol/water boundary (pH 7.4),
      suggesting that channel suppression is mediated by a partitioning of TCA into the
      lipid bilayer of plasma membranes. The rank order of suppression matched human
      recognition of off-flavors: TCA equivalent to 2,4,6-tribromoanisole, which is
      much greater than 2,4,6-trichlorophenol. Furthermore, TCA was detected in a wide
      variety of foods and beverages surveyed for odor losses. Our findings demonstrate
      a potential molecular mechanism for the reduction of flavor. 

PMID- 24043821
TI  - High-resolution reversible folding of hyperstable RNA tetraloops using molecular
      dynamics simulations.
AB  - We report the de novo folding of three hyperstable RNA tetraloops to 1-3 A rmsd
      from their experimentally determined structures using molecular dynamics
      simulations initialized in the unfolded state. RNA tetraloops with loop sequences
      UUCG, GCAA, or CUUG are hyperstable because of the formation of noncanonical loop
      stabilizing interactions, and they are all faithfully reproduced to angstrom
      level accuracy in replica exchange molecular dynamics simulations, including
      explicit solvent and ion molecules. This accuracy is accomplished using unique
      RNA parameters, in which biases that favor rigid, highly stacked conformations
      are corrected to accurately capture the inherent flexibility of ssRNA loops,
      accurate base stacking energetics, and purine syn-anti interconversions. In a
      departure from traditional quantum chemistrycentric approaches to force field
      optimization, our parameters are calibrated directly from thermodynamic and
      kinetic measurements of intra- and internucleotide structural transitions. The
      ability to recapitulate the signature noncanonical interactions of the three most
      abundant hyperstable stem loop motifs represents a significant milestone to the
      accurate prediction of RNA tertiary structure using unbiased all-atom molecular
      dynamics simulations. 

PMID- 24043820
TI  - Multiscaled exploration of coupled folding and binding of an intrinsically
      disordered molecular recognition element in measles virus nucleoprotein.
AB  - Numerous relatively short regions within intrinsically disordered proteins (IDPs)
      serve as molecular recognition elements (MoREs). They fold into ordered
      structures upon binding to their partner molecules. Currently, there is still a
      lack of in-depth understanding of how coupled binding and folding occurs in
      MoREs. Here, we quantified the unbound ensembles of the alpha-MoRE within the
      intrinsically disordered C-terminal domain of the measles virus nucleoprotein. We
      developed a multiscaled approach by combining a physics-based and an atomic
      hybrid model to decipher the mechanism by which the alpha-MoRE interacts with the
      X domain of the measles virus phosphoprotein. Our multiscaled approach led to
      remarkable qualitative and quantitative agreements between the theoretical
      predictions and experimental results (e.g., chemical shifts). We found that the
      free alpha-MoRE rapidly interconverts between multiple discrete partially helical
      conformations and the unfolded state, in accordance with the experimental
      observations. We quantified the underlying global folding-binding landscape. This
      leads to a synergistic mechanism in which the recognition event proceeds via
      (minor) conformational selection, followed by (major) induced folding. We also
      provided evidence that the alpha-MoRE is a compact molten globule-like IDP and
      behaves as a downhill folder in the induced folding process. We further provided
      a theoretical explanation for the inherent connections between "downhill
      folding," "molten globule," and "intrinsic disorder" in IDP-related systems.
      Particularly, we proposed that binding and unbinding of IDPs proceed in a
      stepwise way through a "kinetic divide-and-conquer" strategy that confers them
      high specificity without high affinity. 

PMID- 24043822
TI  - Sensorimotor structure of Drosophila larva phototaxis.
AB  - The avoidance of light by fly larvae is a classic paradigm for sensorimotor
      behavior. Here, we use behavioral assays and video microscopy to quantify the
      sensorimotor structure of phototaxis using the Drosophila larva. Larval
      locomotion is composed of sequences of runs (periods of forward movement) that
      are interrupted by abrupt turns, during which the larva pauses and sweeps its
      head back and forth, probing local light information to determine the direction
      of the successive run. All phototactic responses are mediated by the same set of
      sensorimotor transformations that require temporal processing of sensory inputs.
      Through functional imaging and genetic inactivation of specific neurons
      downstream of the sensory periphery, we have begun to map these sensorimotor
      circuits into the larval central brain. We find that specific sensorimotor
      pathways that govern distinct light-evoked responses begin to segregate at the
      first relay after the photosensory neurons. 

PMID- 24043823
TI  - Localizing transcripts to single cells suggests an important role of uncultured
      deltaproteobacteria in the termite gut hydrogen economy.
AB  - Identifying microbes responsible for particular environmental functions is
      challenging, given that most environments contain an uncultivated microbial
      diversity. Here we combined approaches to identify bacteria expressing genes
      relevant to catabolite flow and to locate these genes within their environment,
      in this case the gut of a "lower," wood-feeding termite. First, environmental
      transcriptomics revealed that 2 of the 23 formate dehydrogenase (FDH) genes known
      in the system accounted for slightly more than one-half of environmental
      transcripts. FDH is an essential enzyme of H2 metabolism that is ultimately
      important for the assimilation of lignocellulose-derived energy by the insect.
      Second, single-cell PCR analysis revealed that two different bacterial types
      expressed these two transcripts. The most commonly transcribed FDH in situ is
      encoded by a previously unappreciated deltaproteobacterium, whereas the other FDH
      is spirochetal. Third, PCR analysis of fractionated gut contents demonstrated
      that these bacteria reside in different spatial niches; the spirochete is free
      swimming, whereas the deltaproteobacterium associates with particulates. Fourth,
      the deltaproteobacteria expressing FDH were localized to protozoa via
      hybridization chain reaction-FISH, an approach for multiplexed, spatial mapping
      of mRNA and rRNA targets. These results underscore the importance of making
      direct vs. inference-based gene-species associations, and have implications in
      higher termites, the most successful termite lineage, in which protozoa have been
      lost from the gut community. Contrary to expectations, in higher termites, FDH
      genes related to those from the protozoan symbiont dominate, whereas most others
      were absent, suggesting that a successful gene variant can persist and flourish
      after a gut perturbation alters a major environmental niche. 

PMID- 24043824
TI  - NFAT5 induction by the pre-T-cell receptor serves as a selective survival signal
      in T-lymphocyte development.
AB  - The Rel-like transcription factors nuclear factor kappa B (NF-kappaB) and the
      calcineurin-dependent nuclear factor of activated T cells (NFATc) control
      specific points of thymocyte maturation. Thymocytes also express a distinct
      member of the Rel family, the calcineurin-independent, osmostress response
      regulator NFAT5. Here we show that IKKbeta regulates the expression of NFAT5 in
      thymocytes, which in turn contributes to the survival of T-cell receptor
      alphabeta thymocytes and the transition from the beta-selection checkpoint to the
      double-positive stage in an osmostress-independent manner. NFAT5-deficient
      thymocytes had normal expression and proximal signaling of the pre-T-cell
      receptor but exhibited a partial defect in beta-chain allelic exclusion and
      increased apoptosis. Further analysis showed that NFAT5 regulated the expression
      of the prosurvival factors A1 and Bcl2 and attenuated the proapoptotic p53/Noxa
      axis. These findings position NFAT5 as a target of the IKKbeta/NF-kappaB pathway
      in thymocytes and as a downstream effector of the prosurvival role of the pre-T
      cell receptor. 

PMID- 24043825
TI  - Dendritic growth gated by a steroid hormone receptor underlies increases in
      activity in the developing Drosophila locomotor system.
AB  - As animals grow, their nervous systems also increase in size. How growth in the
      central nervous system is regulated and its functional consequences are
      incompletely understood. We explored these questions, using the larval Drosophila
      locomotor system as a model. In the periphery, at neuromuscular junctions,
      motoneurons are known to enlarge their presynaptic axon terminals in size and
      strength, thereby compensating for reductions in muscle excitability that are
      associated with increases in muscle size. Here, we studied how motoneurons change
      in the central nervous system during periods of animal growth. We find that
      within the central nervous system motoneurons also enlarge their postsynaptic
      dendritic arbors, by the net addition of branches, and that these scale with
      overall animal size. This dendritic growth is gated on a cell-by-cell basis by a
      specific isoform of the steroid hormone receptor ecdysone receptor-B2, for which
      functions have thus far remained elusive. The dendritic growth is accompanied by
      synaptic strengthening and results in increased neuronal activity. Electrical
      properties of these neurons, however, are independent of ecdysone receptor-B2
      regulation. We propose that these structural dendritic changes in the central
      nervous system, which regulate neuronal activity, constitute an additional part
      of the adaptive response of the locomotor system to increases in body and muscle
      size as the animal grows. 

PMID- 24043826
TI  - GPR171 is a hypothalamic G protein-coupled receptor for BigLEN, a neuropeptide
      involved in feeding.
AB  - Multiple peptide systems, including neuropeptide Y, leptin, ghrelin, and others,
      are involved with the control of food intake and body weight. The peptide
      LENSSPQAPARRLLPP (BigLEN) has been proposed to act through an unknown receptor to
      regulate body weight. In the present study, we used a combination of ligand
      binding and receptor-activity assays to characterize a Galphai/o protein-coupled
      receptor activated by BigLEN in the mouse hypothalamus and Neuro2A cells. We then
      selected orphan G protein-coupled receptors expressed in the hypothalamus and
      Neuro2A cells and tested each for activation by BigLEN. G protein-coupled
      receptor 171 (GPR171) is activated by BigLEN, but not by the C terminally
      truncated peptide LittleLEN. The four C-terminal amino acids of BigLEN are
      sufficient to bind and activate GPR171. Overexpression of GPR171 leads to an
      increase, and knockdown leads to a decrease, in binding and signaling by BigLEN
      and the C-terminal peptide. In the hypothalamus GPR171 expression complements the
      expression of BigLEN, and its level and activity are elevated in mice lacking
      BigLEN. In mice, shRNA-mediated knockdown of hypothalamic GPR171 leads to a
      decrease in BigLEN signaling and results in changes in food intake and
      metabolism. The combination of GPR171 shRNA together with neutralization of
      BigLEN peptide by antibody absorption nearly eliminates acute feeding in food
      deprived mice. Taken together, these results demonstrate that GPR171 is the
      BigLEN receptor and that the BigLEN-GPR171 system plays an important role in
      regulating responses associated with feeding and metabolism in mice. 

PMID- 24043827
TI  - Distortional binding of transition state analogs to human purine nucleoside
      phosphorylase probed by magic angle spinning solid-state NMR.
AB  - Transition state analogs mimic the geometry and electronics of the transition
      state of enzymatic reactions. These molecules bind to the active site of the
      enzyme much tighter than substrate and are powerful noncovalent inhibitors.
      Immucillin-H (ImmH) and 4'-deaza-1'-aza-2'-deoxy-9-methylene Immucillin-H (DADMe
      ImmH) are picomolar inhibitors of human purine nucleoside phosphorylase (hPNP).
      Although both molecules are electronically similar to the oxocarbenium-like
      dissociative hPNP transition state, DADMe-ImmH is more potent than ImmH. DADMe
      ImmH captures more of the transition state binding energy by virtue of being a
      closer geometric match to the hPNP transition state than ImmH. A consequence of
      these similarities is that the active site of hPNP exerts greater distortional
      forces on ImmH than on DADMe-ImmH to "achieve" the hPNP transition state
      geometry. By using magic angle spinning solid-state NMR to investigate stable
      isotope-labeled ImmH and DADMe-ImmH, we have explored the difference in
      distortional binding of these two inhibitors to hPNP. High-precision
      determinations of internuclear distances from NMR recoupling techniques,
      rotational echo double resonance, and rotational resonance, have provided
      unprecedented atomistic insight into the geometric changes that occur upon
      binding of transition state analogs. We conclude that hPNP stabilizes
      conformations of these chemically distinct analogs having distances between the
      cation and leaving groups resembling those of the known transition state. 

PMID- 24043828
TI  - XPLN is an endogenous inhibitor of mTORC2.
AB  - Mammalian target of rapamycin complex 2 (mTORC2) controls a wide range of
      cellular and developmental processes, but its regulation remains incompletely
      understood. Through a yeast two-hybrid screen, we have identified XPLN (exchange
      factor found in platelets, leukemic, and neuronal tissues), a guanine nucleotide
      exchange factor (GEF) for Rho GTPases, as an interacting partner of mTOR. In
      mammalian cells, XPLN interacts with mTORC2 but not with mTORC1, and this
      interaction is dependent on rictor. Knockdown of XPLN enhances phosphorylation of
      the Ser/Thr kinase Akt, a target of mTORC2, whereas overexpression of XPLN
      suppresses it, suggesting that XPLN inhibits mTORC2 signaling to Akt. Consistent
      with Akt promoting cell survival and XPLN playing a negative role in this
      process, XPLN knockdown protects cells from starvation-induced apoptosis.
      Importantly, this effect of XPLN depletion is abolished by inhibition of Akt or
      mTOR kinase activity, as well as by rictor knockdown. In vitro, purified XPLN
      inhibits mTORC2 kinase activity toward Akt without affecting mTORC1 activity.
      Interestingly, the GEF activity of XPLN is dispensable for its regulation of
      mTORC2 and Akt in cells and in vitro, whereas an N-terminal 125-amino-acid
      fragment of XPLN is both necessary and sufficient for the inhibition of mTORC2.
      Finally, as a muscle-enriched protein, XPLN negatively regulates myoblast
      differentiation by suppressing mTORC2 and Akt, and this function is through the
      XPLN N terminus and independent of GEF activity. Our study identifies XPLN as an
      endogenous inhibitor of mTORC2 and delineates a noncanonical mechanism of XPLN
      action. 

PMID- 24043829
TI  - Evidence for at least six Hox clusters in the Japanese lamprey (Lethenteron
      japonicum).
AB  - Cyclostomes, comprising jawless vertebrates such as lampreys and hagfishes, are
      the sister group of living jawed vertebrates (gnathostomes) and hence an
      important group for understanding the origin and diversity of vertebrates. In
      vertebrates and other metazoans, Hox genes determine cell fate along the
      anteroposterior axis of embryos and are implicated in driving morphological
      diversity. Invertebrates contain a single Hox cluster (either intact or
      fragmented), whereas elephant shark, coelacanth, and tetrapods contain four Hox
      clusters owing to two rounds of whole-genome duplication ("1R" and "2R") during
      early vertebrate evolution. By contrast, most teleost fishes contain up to eight
      Hox clusters because of an additional "teleost-specific" genome duplication
      event. By sequencing bacterial artificial chromosome (BAC) clones and the whole
      genome, here we provide evidence for at least six Hox clusters in the Japanese
      lamprey (Lethenteron japonicum). This suggests that the lamprey lineage has
      experienced an additional genome duplication after 1R and 2R. The relative age of
      lamprey and human paralogs supports this hypothesis. Compared with gnathostome
      Hox clusters, lamprey Hox clusters are unusually large. Several conserved
      noncoding elements (CNEs) were predicted in the Hox clusters of lamprey, elephant
      shark, and human. Transgenic zebrafish assay indicated the potential of CNEs to
      function as enhancers. Interestingly, CNEs in individual lamprey Hox clusters are
      frequently conserved in multiple Hox clusters in elephant shark and human,
      implying a many-to-many orthology relationship between lamprey and gnathostome
      Hox clusters. Such a relationship suggests that the first two rounds of genome
      duplication may have occurred independently in the lamprey and gnathostome
      lineages. 

PMID- 24043830
TI  - Carbon substitution for oxygen in silicates in planetary interiors.
AB  - Amorphous silicon oxycarbide polymer-derived ceramics (PDCs), synthesized from
      organometallic precursors, contain carbon- and silica-rich nanodomains, the
      latter with extensive substitution of carbon for oxygen, linking Si-centered
      SiO(x)C(4-x) tetrahedra. Calorimetric studies demonstrated these PDCs to be
      thermodynamically more stable than a mixture of SiO2, C, and silicon carbide.
      Here, we show by multinuclear NMR spectroscopy that substitution of C for O is
      also attained in PDCs with depolymerized silica-rich domains containing lithium,
      associated with SiO(x)C(4-x) tetrahedra with nonbridging oxygen. We suggest that
      significant (several percent) substitution of C for O could occur in more complex
      geological silicate melts/glasses in contact with graphite at moderate pressure
      and high temperature and may be thermodynamically far more accessible than C for
      Si substitution. Carbon incorporation will change the local structure and may
      affect physical properties, such as viscosity. Analogous carbon substitution at
      grain boundaries, at defect sites, or as equilibrium states in nominally
      acarbonaceous crystalline silicates, even if present at levels at 10-100 ppm,
      might form an extensive and hitherto hidden reservoir of carbon in the lower
      crust and mantle.

PMID- 24043831
TI  - Structures of human primase reveal design of nucleotide elongation site and mode
      of Pol alpha tethering.
AB  - Initiation of DNA synthesis in genomic duplication depends on primase, the DNA
      dependent RNA polymerase that synthesizes de novo the oligonucleotides that prime
      DNA replication. Due to the discontinuous nature of DNA replication, primase
      activity on the lagging strand is required throughout the replication process. In
      eukaryotic cells, the presence of primase at the replication fork is secured by
      its physical association with DNA polymerase alpha (Pol alpha), which extends the
      RNA primer with deoxynucleotides. Our knowledge of the mechanism that primes DNA
      synthesis is very limited, as structural information for the eukaryotic enzyme
      has proved difficult to obtain. Here, we describe the crystal structure of human
      primase in heterodimeric form consisting of full-length catalytic subunit and a C
      terminally truncated large subunit. We exploit the crystallographic model to
      define the architecture of its nucleotide elongation site and to show that the
      small subunit integrates primer initiation and elongation within the same set of
      functional residues. Furthermore, we define in atomic detail the mode of
      association of primase to Pol alpha, the critical interaction that keeps primase
      tethered to the eukaryotic replisome. 

PMID- 24043832
TI  - Counting molecules in single organelles with superresolution microscopy allows
      tracking of the endosome maturation trajectory.
AB  - Cells tightly regulate trafficking of intracellular organelles, but a deeper
      understanding of this process is technically limited by our inability to track
      the molecular composition of individual organelles below the diffraction limit in
      size. Here we develop a technique for intracellularly calibrated superresolution
      microscopy that can measure the size of individual organelles as well as
      accurately count absolute numbers of molecules, by correcting for undercounting
      owing to immature fluorescent proteins and overcounting owing to fluorophore
      blinking. Using this technique, we characterized the size of individual vesicles
      in the yeast endocytic pathway and the number of accessible phosphatidylinositol
      3-phosphate binding sites they contain. This analysis reveals a characteristic
      vesicle maturation trajectory of composition and size with both stochastic and
      regulated components. The trajectory displays some cell-to-cell variability, with
      smaller variation between organelles within the same cell. This approach also
      reveals mechanistic information on the order of events in this trajectory:
      Colocalization analysis with known markers of different vesicle maturation stages
      shows that phosphatidylinositol 3-phosphate production precedes fusion into
      larger endosomes. This single-organelle analysis can potentially be applied to a
      range of small organelles to shed light on their precise composition/structure
      relationships, the dynamics of their regulation, and the noise in these
      processes. 

PMID- 24043833
TI  - Structural features of Argonaute-GW182 protein interactions.
AB  - MicroRNAs (miRNAs) guide Argonaute (Ago) proteins to target mRNAs, leading to
      gene silencing. However, Ago proteins are not the actual mediators of gene
      silencing but interact with a member of the GW182 protein family (also known as
      GW proteins), which coordinates all downstream steps in gene silencing. GW
      proteins contain an N-terminal Ago-binding domain that is characterized by
      multiple GW repeats and a C-terminal silencing domain with several globular
      domains. Within the Ago-binding domain, Trp residues mediate the direct
      interaction with the Ago protein. Here, we have characterized the interaction of
      Ago proteins with GW proteins in molecular detail. Using biochemical and NMR
      experiments, we show that only a subset of Trp residues engage in Ago
      interactions. The Trp residues are located in intrinsically disordered regions,
      where flanking residues mediate additional weak interactions, that might explain
      the importance of specific tryptophans. Using cross-linking followed by mass
      spectrometry, we map the GW protein interactions with Ago2, which allows for
      structural modeling of Ago-GW182 interaction. Our data further indicate that the
      Ago-GW protein interaction might be a two-step process involving the sequential
      binding of two tryptophans separated by a spacer with a minimal length of 10 aa. 

PMID- 24043834
TI  - Hierarchical excitatory synaptic connectivity in mouse olfactory cortex.
AB  - Topological motifs in synaptic connectivity-such as the cortical column-are
      fundamental to processing of information in cortical structures. However, the
      mesoscale topology of cortical networks beyond columns remains largely unknown.
      In the olfactory cortex, which lacks an obvious columnar structure, sensory
      evoked patterns of activity have failed to reveal organizational principles of
      the network and its structure has been considered to be random. We probed the
      excitatory network in the mouse olfactory cortex using variance analysis of
      paired whole-cell recording in olfactory cortex slices. On a given trial,
      triggered network-wide bursts in disinhibited slices had remarkably similar time
      courses in widely separated and randomly selected cell pairs of pyramidal neurons
      despite significant trial-to-trial variability within each neuron. Simulated
      excitatory network models with random topologies only partially reproduced the
      experimental burst-variance patterns. Network models with local (columnar) or
      distributed subnetworks, which have been predicted as the basis of encoding odor
      objects, were also inconsistent with the experimental data, showing greater
      variability between cells than across trials. Rather, network models with power
      law and especially hierarchical connectivity showed the best fit. Our results
      suggest that distributed subnetworks are weak or absent in the olfactory cortex,
      whereas a hierarchical excitatory topology may predominate. A hierarchical
      excitatory network organization likely underlies burst generation in this
      epileptogenic region, and may also shape processing of sensory information in the
      olfactory cortex. 

PMID- 24043835
TI  - Inositol polyphosphate multikinase is a transcriptional coactivator required for
      immediate early gene induction.
AB  - Profound induction of immediate early genes (IEGs) by neural activation is a
      critical determinant for plasticity in the brain, but intervening molecular
      signals are not well characterized. We demonstrate that inositol polyphosphate
      multikinase (IPMK) acts noncatalytically as a transcriptional coactivator to
      mediate induction of numerous IEGs. IEG induction by electroconvulsive
      stimulation is virtually abolished in the brains of IPMK-deleted mice, which also
      display deficits in spatial memory. Neural activity stimulates binding of IPMK to
      the histone acetyltransferase CBP and enhances its recruitment to IEG promoters.
      Interestingly, IPMK regulation of CBP recruitment and IEG induction does not
      require its catalytic activities. Dominant-negative constructs, which prevent
      IPMK-CBP binding, substantially decrease IEG induction. As IPMK is ubiquitously
      expressed, its epigenetic regulation of IEGs may influence diverse nonneural and
      neural biologic processes. 

PMID- 24043836
TI  - Implementation of cell-free biological networks at steady state.
AB  - Living cells maintain a steady state of biochemical reaction rates by exchanging
      energy and matter with the environment. These exchanges usually do not occur in
      in vitro systems, which consequently go to chemical equilibrium. This in turn has
      severely constrained the complexity of biological networks that can be
      implemented in vitro. We developed nanoliter-scale microfluidic reactors that
      exchange reagents at dilution rates matching those of dividing bacteria. In these
      reactors we achieved transcription and translation at steady state for 30 h and
      implemented diverse regulatory mechanisms on the transcriptional, translational,
      and posttranslational levels, including RNA polymerases, transcriptional
      repression, translational activation, and proteolysis. We constructed and
      implemented an in vitro genetic oscillator and mapped its phase diagram showing
      that steady-state conditions were necessary to produce oscillations. This reactor
      based approach will allow testing of whether fundamental limits exist to in vitro
      network complexity. 

PMID- 24043837
TI  - Putative antirecombinase Srs2 DNA helicase promotes noncrossover homologous
      recombination avoiding loss of heterozygosity.
AB  - DNA damage alone or DNA replication fork arrest at damaged sites may induce DNA
      double-strand breaks and initiate homologous recombination. This event can result
      in a crossover with a homologous chromosome, causing loss of heterozygosity along
      the chromosome. It is known that Srs2 acts as an antirecombinase at the
      replication fork: it is recruited by the SUMO (a small ubiquitin-related
      modifier)-conjugated DNA-polymerase sliding clamp (PCNA) and interferes with
      Rad51/Rad52-mediated homologous recombination. Here, we report that Srs2 promotes
      another type of homologous recombination that produces noncrossover products
      only, in collaboration with PCNA and Rad51. Srs2 proteins lacking the Rad51
      binding domain, PCNA-SUMO-binding motifs, or ATP hydrolysis-dependent DNA
      helicase activity reduce this noncrossover recombination. However, the removal of
      either the Rad51-binding domain or the PCNA-binding motif strongly increases
      crossovers. Srs2 gene mutations are epistatic to mutations in the PCNA
      modification-related genes encoding PCNA, Siz1 (a SUMO ligase) and Rad6 (a
      ubiquitin-conjugating protein). Knocking out RAD51 blocked this recombination but
      enhanced nonhomologous end-joining. We hypothesize that, during DNA double-strand
      break repair, Srs2 mediates collaboration between the Rad51 nucleofilament and
      PCNA-SUMO and directs the heteroduplex intermediate to DNA synthesis in a moving
      bubble. This Rad51/Rad52/Srs2/PCNA-mediated noncrossover pathway avoids both
      interchromosomal crossover and imprecise end-joining, two potential paths leading
      to loss of heterozygosity, and contributes to genome maintenance and human
      health. 

PMID- 24043838
TI  - Structural basis of regulation and oligomerization of human cystathionine beta
      synthase, the central enzyme of transsulfuration.
AB  - Cystathionine beta-synthase (CBS) controls the flux of sulfur from methionine to
      cysteine, a precursor of glutathione, taurine, and H2S. CBS condenses serine and
      homocysteine to cystathionine with the help of three cofactors, heme, pyridoxal
      5'-phosphate, and S-adenosyl-l-methionine. Inherited deficiency of CBS activity
      causes homocystinuria, the most frequent disorder of sulfur metabolism. We
      present the structure of the human enzyme, discuss the unique arrangement of the
      CBS domains in the C-terminal region, and propose how they interact with the
      catalytic core of the complementary subunit to regulate access to the catalytic
      site. This arrangement clearly contrasts with other proteins containing the CBS
      domain including the recent Drosophila melanogaster CBS structure. The absence of
      large conformational changes and the crystal structure of the partially activated
      pathogenic D444N mutant suggest that the rotation of CBS motifs and relaxation of
      loops delineating the entrance to the catalytic site represent the most likely
      molecular mechanism of CBS activation by S-adenosyl-l-methionine. Moreover, our
      data suggest how tetramers, the native quaternary structure of the mammalian CBS
      enzymes, are formed. Because of its central role in transsulfuration, redox
      status, and H2S biogenesis, CBS represents a very attractive therapeutic target.
      The availability of the structure will help us understand the pathogenicity of
      the numerous missense mutations causing inherited homocystinuria and will allow
      the rational design of compounds modulating CBS activity. 

PMID- 24043839
TI  - Disrupting the clustering of GABAA receptor alpha2 subunits in the frontal cortex
      leads to reduced gamma-power and cognitive deficits.
AB  - In schizophrenia, cognitive dysfunction is highly predictive of poor patient
      outcomes and is not responsive to current medications. Postmortem studies have
      suggested that cognitive deficits in schizophrenia are correlated with
      modifications in the number and size of inhibitory synapses. To test if these
      modifications lead to cognitive deficits, we have created a dominant-negative
      virus [adeno-associated (AAV)-DN1] that disrupts the clustering of gamma
      aminobutyric acid type A receptors (GABA(A)Rs) at postsynaptic inhibitory
      specializations. When injected into the frontal cortex of mice, AAV-DN1 impairs
      GABA(A)R alpha2 subunit and GABA transporter 1 (GAT-1) clustering, but increases
      GABA(A)R alpha1 subunit clustering on the perisomatic region, with no influence
      on axon-initial segment clustering. Mice expressing AAV-DN1 have prepulse
      inhibition deficits and impairments in working memory. Significantly, these
      behavioral deficits are paralleled by a reduction in electroencephalography gamma
      power. Collectively, our study provides functional evidence revealing that
      GABAergic synapses in the prefrontal cortex directly contribute to cognition and
      gamma-power.

PMID- 24043840
TI  - Evidence for a rapid release of carbon at the Paleocene-Eocene thermal maximum.
AB  - The Paleocene/Eocene thermal maximum (PETM) and associated carbon isotope
      excursion (CIE) are often touted as the best geologic analog for the current
      anthropogenic rise in pCO2. However, a causal mechanism for the PETM CIE remains
      unidentified because of large uncertainties in the duration of the CIE's onset.
      Here, we report on a sequence of rhythmic sedimentary couplets comprising the
      Paleocene/Eocene Marlboro Clay (Salisbury Embayment). These couplets have
      corresponding delta(18)O cycles that imply a climatic origin. Seasonal insolation
      is the only regular climate cycle that can plausibly account for delta(18)O
      amplitudes and layer counts. High-resolution stable isotope records show 3.50/00
      delta(13)C decrease over 13 couplets defining the CIE onset, which requires a
      large, instantaneous release of (13)C-depleted carbon. During the CIE, a clear
      delta(13)C gradient developed on the shelf with the largest excursions in
      shallowest waters, indicating atmospheric delta(13)C decreased by ~200/00. Our
      observations and revised release rate are consistent with an atmospheric
      perturbation of 3,000-gigatons of carbon (GtC).

PMID- 24043841
TI  - Electromagnetically driven westward drift and inner-core superrotation in Earth's
      core.
AB  - A 3D numerical model of the earth's core with a viscosity two orders of magnitude
      lower than the state of the art suggests a link between the observed westward
      drift of the magnetic field and superrotation of the inner core. In our model,
      the axial electromagnetic torque has a dominant influence only at the surface and
      in the deepest reaches of the core, where it respectively drives a broad westward
      flow rising to an axisymmetric equatorial jet and imparts an eastward-directed
      torque on the solid inner core. Subtle changes in the structure of the internal
      magnetic field may alter not just the magnitude but the direction of these
      torques. This not only suggests that the quasi-oscillatory nature of inner-core
      superrotation [Tkalcic H, Young M, Bodin T, Ngo S, Sambridge M (2013) The
      shuffling rotation of the earth's inner core revealed by earthquake doublets. Nat
      Geosci 6:497-502.] may be driven by decadal changes in the magnetic field, but
      further that historical periods in which the field exhibited eastward drift were
      contemporaneous with a westward inner-core rotation. The model further indicates
      a strong internal shear layer on the tangent cylinder that may be a source of
      torsional waves inside the core. 

PMID- 24043842
TI  - Network structure and dynamics of the mental workspace.
AB  - The conscious manipulation of mental representations is central to many creative
      and uniquely human abilities. How does the human brain mediate such flexible
      mental operations? Here, multivariate pattern analysis of functional MRI data
      reveals a widespread neural network that performs specific mental manipulations
      on the contents of visual imagery. Evolving patterns of neural activity within
      this mental workspace track the sequence of informational transformations carried
      out by these manipulations. The network switches between distinct connectivity
      profiles as representations are maintained or manipulated. 

PMID- 24043843
TI  - Upbeat nystagmus in anti-Ma2 encephalitis.
AB  - Anti-Ma2 encephalitis is a paraneoplastic disorder characterised by brainstem
      and/or limbic involvement. Eye movement abnormalities can occur in this
      condition, often with confusion or somnolence. We describe a patient with
      progressive oscillopsia (with upbeat nystagmus) and unsteadiness, followed by
      acute pancreatitis. She did not respond to immunomodulatory treatment and
      subsequently died of complications related to pancreatitis and sepsis. There was
      no tumour identified at autopsy, but the anti-Ma2 antibodies in her serum and the
      discovery of a brainstem-predominant inflammatory infiltrate at autopsy strongly
      suggest a paraneoplastic disorder. Our case illustrates that upbeat nystagmus can
      be a predominant feature in anti-Ma2 encephalitis; clinicians should consider
      testing for anti-Ma2 antibodies in patients with upbeat nystagmus of unknown
      cause. 

PMID- 24043844
TI  - Unintentional non-adherence: can a spoon full of resilience help the medicine go
      down?

PMID- 24043845
TI  - Maternal obesity disturbs the postnatal development of gonocytes in the rat
      without impairment of testis structure at prepubertal age.
AB  - In this study, we evaluated whether maternal obesity (MO) affects testis
      development and gonocyte differentiation in the rat from 0.5 to 14.5 postnatal
      days. Male Wistar rats were used at 0.5, 4.5, 7.5, and 14.5 days post partum
      (dpp). These rats were born from obese mothers, previously fed with a high-fat
      diet (20% saturated fat), for 15 weeks, or normal mothers that had received a
      balanced murine diet (4% lipids). MO did not affect testis weight or histology at
      birth but changed the migratory behavior of gonocytes. The density of relocated
      cells was higher in MO pups at 0.5 dpp, decreased at 4.5 dpp, and differed from
      those of control pups, where density increased exponentially from 0.5 to 7.5 dpp.
      The numerical density of gonocytes within seminiferous cords did not vary in MO,
      in relation to control neonates, for any age considered, but the testis weight
      was 50% lower at 4.5 dpp. A wide variation in plasmatic testosterone and estrogen
      levels was observed among the groups during the first week of age and MO pups
      exhibited higher steroid concentrations at 4.5 dpp, in comparison with controls.
      At this age, higher estrogen levels of MO pups impaired the gonocyte
      proliferation. At 7.5 dpp, the testicular size and other parameters of gonocyte
      development are retrieved. In conclusion, MO and saturated lipid diets disturb
      gonocyte development and sexual steroid levels during the first days of life,
      with recovery at prepubertal age. 

PMID- 24043846
TI  - Antioxidant supplementation overcomes the deleterious effects of maternal
      restraint stress-induced oxidative stress on mouse oocytes.
AB  - In this study, using a mouse model, we tested the hypothesis that restraint
      stress would impair the developmental potential of oocytes by causing oxidative
      stress and that antioxidant supplementation could overcome the adverse effect of
      stress-induced oxidative stress. Female mice were subjected to restraint stress
      for 24 h starting 24 h after equine chorionic gonadotropin injection. At the end
      of stress exposure, mice were either killed to recover oocytes for in vitro
      maturation (IVM) or injected with human chorionic gonadotropin and caged with
      male mice to observe in vivo development. The effect of antioxidants was tested
      in vitro by adding them to IVM medium or in vivo by maternal injection
      immediately before restraint stress exposure. Assays carried out to determine
      total oxidant and antioxidant status, oxidative stress index, and reactive oxygen
      species (ROS) and glutathione levels indicated that restraint stress increased
      oxidative stress in mouse serum, ovaries, and oocytes. Whereas the percentage of
      blastocysts and number of cells per blastocyst decreased significantly in oocytes
      from restraint-stressed mice, addition of antioxidants to IVM medium
      significantly improved their blastocyst development. Supplementation of cystine
      and cysteamine to IVM medium reduced ROS levels and aneuploidy while increasing
      glutathione synthesis and improving pre- and postimplantation development of
      oocytes from restraint-stressed mice. Furthermore, injection of the antioxidant
      epigallocatechin gallate into restraint-stressed mice significantly improved the
      blastocyst formation and postimplantation development of their oocytes. In
      conclusion, restraint stress at the oocyte prematuration stage impaired the
      developmental potential of oocytes by increasing oxidative stress and addition of
      antioxidants to IVM medium or maternal antioxidant injection overcame the
      detrimental effect of stress-induced oxidative stress. The data reported herein
      are helpful when making attempts to increase the chances of a successful outcome
      in human IVF, because restraint was applied at a stage similar to the FSH
      stimulation period in a human IVF program. 

PMID- 24043847
TI  - Making open data work for plant scientists.
AB  - Despite the clear demand for open data sharing, its implementation within plant
      science is still limited. This is, at least in part, because open data-sharing
      raises several unanswered questions and challenges to current research practices.
      In this commentary, some of the challenges encountered by plant researchers at
      the bench when generating, interpreting, and attempting to disseminate their data
      have been highlighted. The difficulties involved in sharing sequencing,
      transcriptomics, proteomics, and metabolomics data are reviewed. The benefits and
      drawbacks of three data-sharing venues currently available to plant scientists
      are identified and assessed: (i) journal publication; (ii) university
      repositories; and (iii) community and project-specific databases. It is concluded
      that community and project-specific databases are the most useful to researchers
      interested in effective data sharing, since these databases are explicitly
      created to meet the researchers' needs, support extensive curation, and embody a
      heightened awareness of what it takes to make data reuseable by others. Such
      bottom-up and community-driven approaches need to be valued by the research
      community, supported by publishers, and provided with long-term sustainable
      support by funding bodies and government. At the same time, these databases need
      to be linked to generic databases where possible, in order to be discoverable to
      the majority of researchers and thus promote effective and efficient data
      sharing. As we look forward to a future that embraces open access to data and
      publications, it is essential that data policies, data curation, data
      integration, data infrastructure, and data funding are linked together so as to
      foster data access and research productivity. 

PMID- 24043848
TI  - LEA polypeptide profiling of recalcitrant and orthodox legume seeds reveals ABI3
      regulated LEA protein abundance linked to desiccation tolerance.
AB  - In contrast to orthodox seeds that acquire desiccation tolerance during
      maturation, recalcitrant seeds are unable to survive drying. These desiccation
      sensitive seeds constitute an interesting model for comparative analysis with
      phylogenetically close species that are desiccation tolerant. Considering the
      importance of LEA (late embryogenesis abundant) proteins as protective molecules
      both in drought and in desiccation tolerance, the heat-stable proteome was
      characterized in cotyledons of the legume Castanospermum australe and it was
      compared with that of the orthodox model legume Medicago truncatula. RNA
      sequencing identified transcripts of 16 homologues out of 17 LEA genes for which
      polypeptides are detected in M. truncatula seeds. It is shown that for 12 LEA
      genes, polypeptides were either absent or strongly reduced in C. australe
      cotyledons compared with M. truncatula seeds. Instead, osmotically responsive,
      non-seed-specific dehydrins accumulated to high levels in the recalcitrant
      cotyledons compared with orthodox seeds. Next, M. truncatula mutants of the
      abscisic acid insensitive3 (ABI3) gene were characterized. Mature Mtabi3 seeds
      were found to be desiccation sensitive when dried below a critical water content
      of 0.4 g H2O g DW(-1). Characterization of the LEA proteome of the Mtabi3 seeds
      revealed a subset of LEA proteins with severely reduced abundance that were also
      found to be reduced or absent in C. australe cotyledons. Transcripts of these
      genes were indeed shown to be ABI3 responsive. The results highlight those LEA
      proteins that are critical to desiccation tolerance and suggest that comparable
      regulatory pathways responsible for their accumulation are missing in both
      desiccation-sensitive genotypes, revealing new insights into the mechanistic
      basis of the recalcitrant trait in seeds.

PMID- 24043849
TI  - Root ethylene signalling is involved in Miscanthus sinensis growth promotion by
      the bacterial endophyte Herbaspirillum frisingense GSF30(T).
AB  - The bacterial endophyte Herbaspirillum frisingense GSF30(T) is a colonizer of
      several grasses grown in temperate climates, including the highly nitrogen
      efficient perennial energy grass Miscanthus. Inoculation of Miscanthus sinensis
      seedlings with H. frisingense promoted root and shoot growth but had only a minor
      impact on nutrient concentrations. The bacterium affected the root architecture
      and increased fine-root structures. Although H. frisingense has the genetic
      requirements to fix nitrogen, only minor changes in nitrogen concentrations were
      observed. Herbaspirillum agglomerates were identified primarily in the root
      apoplast but also in the shoots. The short-term (3h) and long-term (3 weeks)
      transcriptomic responses of the plant to bacterial inoculation revealed that H.
      frisingense induced rapid changes in plant hormone signalling, most prominent in
      jasmonate signalling. Ethylene signalling pathways were also affected and
      persisted after 3 weeks in the root. Growth stimulation of the root by the
      ethylene precursor 1-aminocyclopropane 1-carboxylic acid was dose dependent and
      was affected by H. frisingense inoculation. Minor changes in the proteome were
      identified after 3 weeks. This study suggests that H. frisingense improves plant
      growth by modulating plant hormone signalling pathways and provides a framework
      to understand the beneficial effects of diazotrophic plant-growth-promoting
      bacteria, such as H. frisingense, on the biomass grass Miscanthus. 

PMID- 24043850
TI  - Grapevine NAC1 transcription factor as a convergent node in developmental
      processes, abiotic stresses, and necrotrophic/biotrophic pathogen tolerance.
AB  - Transcription factors of the NAC family are known to be involved in various
      developmental processes and in response to environmental stresses. Whereas NAC
      genes have been widely studied in response to abiotic stresses, little is known
      about their role in response to biotic stresses, especially in crops. Here, the
      first characterization of a Vitis vinifera L. NAC member, named VvNAC1, and
      involved in organ development and defence towards pathogens is reported.
      Expression profile analysis of VvNAC1 showed that its expression is closely
      associated with later stages of leaf, flower, and berry development, suggesting a
      role in plant senescence. Moreover, VvNAC1 expression is stimulated in Botrytis
      cinerea- or microbe-associated molecular pattern (MAMP)-infected berries or
      leaves. Furthermore, cold, wounding, and defence-related hormones such as
      salicylic acid, methyl jasmonate, ethylene, and abscisic acid are all able to
      induce VvNAC1 expression in grapevine leaves. VvNAC1-overexpressing Arabidopsis
      plants exhibit enhanced tolerance to osmotic, salt, and cold stresses and to B.
      cinerea and Hyaloperonospora arabidopsidis pathogens. These plants present a
      modified pattern of defence gene markers (AtPR-1, AtPDF1.2, and AtVSP1) after
      stress application, suggesting that VvNAC1 is an important regulatory component
      of the plant signalling defence cascade. Collectively, these results provide
      evidence that VvNAC1 could represent a node of convergence regulating grapevine
      development and stress responses, including defence against necrotrophic and
      biotrophic pathogens. 

PMID- 24043851
TI  - Asymmetric growth of root epidermal cells is related to the differentiation of
      root hair cells in Hordeum vulgare (L.).
AB  - The root epidermis of most vascular plants harbours two cell types, namely
      trichoblasts (capable of producing a root hair) and atrichoblasts. Here, in vivo
      analysis, confocal laser-scanning microscopy, transmission electron microscopy,
      histological analysis, and three-dimensional reconstruction were used to
      characterize the cell types present in the barley root epidermis and their
      distribution in the tissue. Both trichoblasts and atrichoblasts were present in
      the wild-type cultivars and could be distinguished from one another at an early
      stage. Trichoblast/atrichoblast differentiation depended on asymmetric cell
      expansion after a period of symmetrical cell division. After asymmetric growth,
      only the shorter epidermal cells could produce root hairs, whereas the longer
      cells became atrichoblasts. Moreover, the root epidermis did not develop root
      hairs at all if the epidermal cells did not differentiate into two asymmetric
      cell types. The root hairless phenotype of bald root barley (brb) and root
      hairless 1.b (rhl1.b) mutants was caused by a mutation in a gene related to the
      asymmetric expansion of the root epidermal cells. Additionally, the results
      showed that the mechanism of trichoblast/atrichoblast differentiation is not
      evolutionally conserved across the subfamilies of the Poaceae; in the Pooideae
      subfamily, both asymmetric division and asymmetric cell expansion have been
      observed. 

PMID- 24043852
TI  - How do roots elongate in a structured soil?
AB  - In this review, we examine how roots penetrate a structured soil. We first
      examine the relationship between soil water status and its mechanical strength,
      as well as the ability of the soil to supply water to the root. We identify these
      as critical soil factors, because it is primarily in drying soil that mechanical
      constraints limit root elongation. Water supply to the root is important because
      root water status affects growth pressures and root stiffness. To simplify the
      bewildering complexity of soil-root interactions, the discussion is focused
      around the special cases of root elongation in soil with pores much smaller than
      the root diameter and the penetration of roots at interfaces within the soil.
      While it is often assumed that the former case is well understood, many
      unanswered questions remain. While low soil-root friction is often viewed as a
      trait conferring better penetration of strong soils, it may also increase the
      axial pressure on the root tip and in so doing reduce the rate of cell division
      and/or expansion. The precise trade-off between various root traits involved in
      root elongation in homogeneous soil remains to be determined. There is consensus
      that the most important factors determining root penetration at an interface are
      the angle at which the root attempts to penetrate the soil, root stiffness, and
      the strength of the soil to be penetrated. The effect of growth angle on root
      penetration implicates gravitropic responses in improved root penetration
      ability. Although there is no work that has explored the effect of the strength
      of the gravitropic responses on penetration of hard layers, we attempt to outline
      possible interactions. Impacts of soil drying and strength on phytohormone
      concentrations in roots, and consequent root-to-shoot signalling, are also
      considered. 

PMID- 24043853
TI  - WRKY76 is a rice transcriptional repressor playing opposite roles in blast
      disease resistance and cold stress tolerance.
AB  - OsWRKY76 encodes a group IIa WRKY transcription factor of rice. The expression of
      OsWRKY76 was induced within 48h after inoculation with rice blast fungus
      (Magnaporthe oryzae), and by wounding, low temperature, benzothiadiazole, and
      abscisic acid. Green fluorescent protein-fused OsWRKY76 localized to the nuclei
      in rice epidermal cells. OsWRKY76 showed sequence-specific DNA binding to the W
      box element in vitro and exhibited W-box-mediated transcriptional repressor
      activity in cultured rice cells. Overexpression of OsWRKY76 in rice plants
      resulted in drastically increased susceptibility to M. oryzae, but improved
      tolerance to cold stress. Microarray analysis revealed that overexpression of
      OsWRKY76 suppresses the induction of a specific set of PR genes and of genes
      involved in phytoalexin synthesis after inoculation with blast fungus, consistent
      with the observation that the levels of phytoalexins in the transgenic rice
      plants remained significantly lower than those in non-transformed control plants.
      Furthermore, overexpression of OsWRKY76 led to the increased expression of
      abiotic stress-associated genes such as peroxidase and lipid metabolism genes.
      These results strongly suggest that OsWRKY76 plays dual and opposing roles in
      blast disease resistance and cold tolerance. 

PMID- 24043854
TI  - A CLE-WOX signalling module regulates root meristem maintenance and vascular
      tissue development in rice.
AB  - CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR)-related (CLE) proteins belong
      to a small peptide family conserved in plants. Recent studies in Arabidopsis and
      rice have revealed a key role for CLEs in mediating cell-cell communication and
      stem cell maintenance during plant development, but how CLE signalling controls
      root development in the rice remains largely unknown. Here it is shown that
      exogenous application of a synthetic dodeca-amino acid peptide corresponding to
      the CLE motif of the rice FON2-LIKE CLE PROTEIN2 (FCP2p) protein or
      overexpression of FCP2 terminates root apical meristem (RAM) activity and impairs
      late metaxylem formation. FCP2p treatment suppresses the expression of the rice
      QUIESCENT-CENTER-SPECIFIC HOMEOBOX (QHB) gene, a putative orthologue of
      Arabidopsis WUSCHEL (WUS)-RELATED HOMEOBOX 5 (WOX5) gene, in both quiescent
      centre and late metaxylem cells; whereas inducible overexpression of QHB reduces
      the sensitivity of rice to FCP2p treatment. These results together suggest that
      in rice RAM maintenance and late metaxylem development are probably controlled by
      the mutual regulation between FCP2 and QHB. Moreover, a cross-species peptide
      treatment experiment in Arabidopsis implies that FCP2 has both evolutionarily
      conserved and species-specific roles in root development. 

PMID- 24043855
TI  - Mining the genome of Arabidopsis thaliana as a basis for the identification of
      novel bioactive peptides involved in oxidative stress tolerance.
AB  - Although evidence has accumulated on the role of plant peptides in the response
      to external conditions, the number of peptide-encoding genes in the genome is
      still underestimated. Using tiling arrays, we identified 176 unannotated
      transcriptionally active regions (TARs) in Arabidopsis thaliana that were induced
      upon oxidative stress generated by the herbicide paraquat (PQ). These 176 TARs
      could be translated into 575 putative oxidative stress-induced peptides (OSIPs).
      A high-throughput functional assay was used in the eukaryotic model organism
      Saccharomyces cerevisiae allowing us to test for bioactive peptides that increase
      oxidative stress tolerance. In this way, we identified three OSIPs that, upon
      overexpression in yeast, resulted in a significant rise in tolerance to hydrogen
      peroxide (H2O2). For one of these peptides, the decapeptide OSIP108, exogenous
      application to H2O2-treated yeast also resulted in significantly increased
      survival. OSIP108 is contained within a pseudogene and is induced in A. thaliana
      leaves by both the reactive oxygen species-inducer PQ and the necrotrophic fungal
      pathogen Botrytis cinerea. Moreover, infiltration and overexpression of OSIP108
      in A. thaliana leaves resulted in increased tolerance to treatment with PQ. In
      conclusion, the identification and characterization of OSIP108 confirms the
      validity of our high-throughput approach, based on tiling array analysis in A.
      thaliana and functional screening in yeast, to identify bioactive peptides. 

PMID- 24043856
TI  - Four genes encoding MYB28, a major transcriptional regulator of the aliphatic
      glucosinolate pathway, are differentially expressed in the allopolyploid Brassica
      juncea.
AB  - Glucosinolates are Capparales-specific secondary metabolites that have immense
      potential in human health and agriculture. Unlike Arabidopsis thaliana, our
      knowledge about glucosinolate regulators in the Brassica crops is sparse. In the
      current study, four MYB28 homologues were identified (BjuMYB28-1,-2,-3,-4) from
      the polyploid Brassica juncea, and the effects of allopolyploidization on the
      divergence of gene sequence, structure, function, and expression were assessed.
      The deduced protein sequences of the four BjuMYB28 genes showed 76.1-83.1%
      identity with the Arabidopsis MYB28. Phylogenetic analysis revealed that the four
      BjuMYB28 proteins have evolved via the hybridization and duplication processes
      forming the B. juncea genome (AABB) from B. rapa (AA) and B. nigra (BB), while
      retaining high levels of sequence conservation. Mutant complementation and over
      expression studies in A. thaliana showed that all four BjuMYB28 genes encode
      functional MYB28 proteins and resulted in similar aliphatic glucosinolate
      composition and content. Detailed expression analysis using qRT-PCR assays and
      promoter-GUS lines revealed that the BjuMYB28 genes have both tissue- and cell
      specific expression partitioning in B. juncea. The two B-genome origin BjuMYB28
      genes had more abundant transcripts during the early stages of plant development
      than the A-genome origin genes. However, with the onset of the reproductive
      phase, expression levels of all four BjuMYB28 increased significantly, which may
      be necessary for producing and maintaining high amounts of aliphatic
      glucosinolates during the later stages of plant development. Taken together, our
      results suggest that the four MYB28 genes are differentially expressed and
      regulated in B. juncea to play discrete though overlapping roles in controlling
      aliphatic glucosinolate biosynthesis. 

PMID- 24043857
TI  - A novel system for spatial and temporal imaging of intrinsic plant water use
      efficiency.
AB  - Instrumentation and methods for rapid screening and selection of plants with
      improved water use efficiency are essential to address current issues of global
      food and fuel security. A new imaging system that combines chlorophyll
      fluorescence and thermal imaging has been developed to generate images of
      assimilation rate (A), stomatal conductance (gs), and intrinsic water use
      efficiency (WUEi) from whole plants or leaves under controlled environmental
      conditions. This is the first demonstration of the production of images of WUEi
      and the first to determine images of g s from themography at the whole-plant
      scale. Data are presented illustrating the use of this system for rapidly and non
      destructively screening plants for alterations in WUEi by comparing Arabidopsis
      thaliana mutants (OST1-1) that have altered WUEi driven by open stomata, with
      wild-type plants. This novel instrument not only provides the potential to
      monitor multiple plants simultaneously, but enables intra- and interspecies
      variation to be taken into account both spatially and temporally. The ability to
      measure A, gs, and WUEi progressively was developed to facilitate and encourage
      the development of new dynamic protocols. Images illustrating the instrument's
      dynamic capabilities are demonstrated by analysing plant responses to changing
      photosynthetic photon flux density (PPFD). Applications of this system will
      augment the research community's need for novel screening methods to identify
      rapidly novel lines, cultivars, or species with improved A and WUEi in order to
      meet the current demands on modern agriculture and food production.

PMID- 24043858
TI  - Domain-domain interactions in ion channels.

PMID- 24043859
TI  - A computational study of barium blockades in the KcsA potassium channel based on
      multi-ion potential of mean force calculations and free energy perturbation.
AB  - Electrophysiological studies have established that the permeation of Ba(2+) ions
      through the KcsA K(+)-channel is impeded by the presence of K(+) ions in the
      external solution, while no effect is observed for external Na(+) ions. This
      Ba(2+) "lock-in" effect suggests that at least one of the external binding sites
      of the KcsA channel is thermodynamically selective for K(+). We used molecular
      dynamics simulations to interpret these lock-in experiments in the context of the
      crystallographic structure of KcsA. Assuming that the Ba(2+) is bound in site
      S(2) in the dominant blocked state, we examine the conditions that could impede
      its translocation and cause the observed "lock-in" effect. Although the binding
      of a K(+) ion to site S(1) when site S(2) is occupied by Ba(2+) is prohibitively
      high in energy (>10 kcal/mol), binding to site S0 appears to be more plausible
      (DeltaG > 4 kcal/mol). The 2D potential of mean force (PMF) for the simultaneous
      translocation of Ba(2+) from site S(2) to site S(1) and of a K(+) ion on the
      extracellular side shows a barrier that is consistent with the concept of
      external lock-in. The barrier opposing the movement of Ba(2+) is very high when a
      cation is in site S(0), and considerably smaller when the site is unoccupied.
      Furthermore, free energy perturbation calculations show that site S(0) is
      selective for K(+) by 1.8 kcal/mol when S(2) is occupied by Ba(2+). However, the
      same site S(0) is nonselective when site S(2) is occupied by K(+), which shows
      that the presence of Ba(2+) affects the selectivity of the pore. A theoretical
      framework within classical rate theory is presented to incorporate the
      concentration dependence of the external ions on the lock-in effect.

PMID- 24043860
TI  - Direct interaction of eag domains and cyclic nucleotide-binding homology domains
      regulate deactivation gating in hERG channels.
AB  - Human ether-a-go-go (eag)-related gene (hERG) potassium channels play a critical
      role in cardiac repolarization and are characterized by unusually slow closing
      (deactivation) kinetics. The N-terminal "eag" domain and a C-terminal C
      linker/cyclic nucleotide-binding homology domain (CNBHD) are required for
      regulation of slow deactivation. The region between the S4 and S5 transmembrane
      domains (S4-S5 linker) is also implicated in this process, but the mechanism for
      regulation of slow deactivation is unclear. Here, using an eag domain-deleted
      channel (hERG Deltaeag) fused to Citrine fluorescent protein, we found that most
      channels bearing individual alanine mutations in the S4-S5 linker were directly
      regulated by recombinant eag domains fused to a cyan fluorescent protein (N-eag
      CFP) and had robust Forster resonance energy transfer (FRET). Additionally, a
      channel bearing a group of eight alanine residues in the S4-S5 linker was not
      measurably regulated by N-eag-CFP domains, but robust FRET was measured. These
      findings demonstrate that the eag domain associated with all of the S4-S5 linker
      mutant channels. In contrast, channels that also lacked the CNBHD (hERG Deltaeag
      DeltaCNBHD-Citrine) were not measurably regulated by N-eag-CFP nor was FRET
      detected, suggesting that the C-linker/CNBHD was required for eag domains to
      directly associate with the channel. In a FRET hybridization assay, N-eag-CFP had
      robust FRET with a C-linker/CNBHD-Citrine, suggesting a direct and specific
      interaction between the eag domain and the C-linker/CNBHD. Lastly, coexpression
      of a hERG subunit lacking the CNBHD and the distal C-terminal region (hERG
      DeltapCT-Citrine) with hERG Deltaeag-CFP subunits had FRET and partial
      restoration of slow deactivation. Collectively, these findings reveal that the C
      linker/CNBHD, but not the S4-S5 linker, was necessary for the eag domain to
      associate with the channel, that the eag domain and the C-linker/CNBHD were
      sufficient for a direct interaction, and that an intersubunit interaction between
      the eag domain and the C-linker/CNBHD regulated slow deactivation in hERG
      channels at the plasma membrane. 

PMID- 24043861
TI  - Tuning voltage-gated channel activity and cellular excitability with a
      sphingomyelinase.
AB  - Voltage-gated ion channels generate action potentials in excitable cells and help
      set the resting membrane potential in nonexcitable cells like lymphocytes. It has
      been difficult to investigate what kinds of phospholipids interact with these
      membrane proteins in their native environments and what functional impacts such
      interactions create. This problem might be circumvented if we could modify
      specific lipid types in situ. Using certain voltage-gated K(+) (KV) channels
      heterologously expressed in Xenopus laevis oocytes as a model, our group has
      shown previously that sphingomyelinase (SMase) D may serve this purpose. SMase D
      is known to remove the choline group from sphingomyelin, a phospholipid primarily
      present in the outer leaflet of plasma membranes. This SMase D action lowers the
      energy required for voltage sensors of a KV channel to enter the activated state,
      causing a hyperpolarizing shift of the Q-V and G-V curves and thus activating
      them at more hyperpolarized potentials. Here, we find that this SMase D effect
      vanishes after removing most of the voltage-sensor paddle sequence, a finding
      supporting the notion that SMase D modification of sphingomyelin molecules alters
      these lipids' interactions with voltage sensors. Then, using SMase D to probe
      lipid-channel interactions, we find that SMase D not only similarly stimulates
      voltage-gated Na(+) (Na(V)) and Ca(2+) channels but also markedly slows Na(V)
      channel inactivation. However, the latter effect is not observed in tested
      mammalian cells, an observation highlighting the profound impact of the membrane
      environment on channel function. Finally, we directly demonstrate that SMase D
      stimulates both native K(V)1.3 in nonexcitable human T lymphocytes at their
      typical resting membrane potential and native Na(V) channels in excitable cells,
      such that it shifts the action potential threshold in the hyperpolarized
      direction. These proof-of-concept studies illustrate that the voltage-gated
      channel activity in both excitable and nonexcitable cells can be tuned by
      enzymatically modifying lipid head groups.

PMID- 24043863
TI  - Long-term legacy of massive carbon input to the Earth system: Anthropocene versus
      Eocene.
AB  - Over the next few centuries, with unabated emissions of anthropogenic carbon
      dioxide (CO2), a total of 5000 Pg C may enter the atmosphere, causing CO2
      concentrations to rise to approximately 2000 ppmv, global temperature to warm by
      more than 8( degrees )C and surface ocean pH to decline by approximately 0.7
      units. A carbon release of this magnitude is unprecedented during the past 56
      million years-and the outcome accordingly difficult to predict. In this regard,
      the geological record may provide foresight to how the Earth system will respond
      in the future. Here, we discuss the long-term legacy of massive carbon release
      into the Earth's surface reservoirs, comparing the Anthropocene with a past
      analogue, the Palaeocene-Eocene Thermal Maximum (PETM, approx. 56 Ma). We examine
      the natural processes and time scales of CO2 neutralization that determine the
      atmospheric lifetime of CO2 in response to carbon release. We compare the
      duration of carbon release during the Anthropocene versus PETM and the ensuing
      effects on ocean acidification and marine calcifying organisms. We also discuss
      the conundrum that the observed duration of the PETM appears to be much longer
      than predicted by models that use first-order assumptions. Finally, we comment on
      past and future mass extinctions and recovery times of biotic diversity. 

PMID- 24043862
TI  - Divergent effects of alpha- and beta-myosin heavy chain isoforms on the N
      terminus of rat cardiac troponin T.
AB  - Divergent effects of alpha- and beta-myosin heavy chain (MHC) isoforms on
      contractile behavior arise mainly because of their impact on thin filament
      cooperativity. The N terminus of cardiac troponin T (cTnT) also modulates thin
      filament cooperativity. Our hypothesis is that the impact of the N terminus of
      cTnT on thin filament activation is modulated by a shift from alpha- to beta-MHC
      isoform. We engineered two recombinant proteins by deleting residues 1-43 and 44
      73 in rat cTnT (RcTnT): RcTnT(1-43Delta) and RcTnT(44-73Delta), respectively.
      Dynamic and steady-state contractile parameters were measured at sarcomere length
      of 2.3 um after reconstituting proteins into detergent-skinned muscle fibers from
      normal (alpha-MHC) and propylthiouracil-treated (beta-MHC) rat hearts. alpha-MHC
      attenuated Ca(2+)-activated maximal tension (~46%) in RcTnT(1-43Delta) fibers. In
      contrast, beta-MHC decreased tension only by 19% in RcTnT(1-43Delta) fibers. Both
      alpha- and beta-MHC did not affect tension in RcTnT(44-73Delta) fibers. The
      instantaneous muscle fiber stiffness measurements corroborated the divergent
      impact of alpha- and beta-MHC on tension in RcTnT(1-43Delta) fibers. pCa50 (-log
      of [Ca(2+)]free required for half-maximal activation) decreased significantly by
      0.13 pCa units in alpha-MHC + RcTnT(1-43Delta) fibers but remained unaltered in
      beta-MHC + RcTnT(1-43Delta) fibers, demonstrating that beta-MHC counteracted the
      attenuating effect of RcTnT(1-43Delta) on myofilament Ca(2+) sensitivity. beta
      MHC did not alter the sudden stretch-mediated recruitment of new cross-bridges
      (ER) in RcTnT(1-43Delta) fibers, but alpha-MHC attenuated ER by 36% in RcTnT(1
      43Delta) fibers. The divergent impact of alpha- and beta-MHC on how the N
      terminus of cTnT modulates contractile dynamics has implications for heart
      disease; alterations in cTnT and MHC are known to occur via changes in isoform
      expression or mutations.

PMID- 24043864
TI  - Climate sensitivity, sea level and atmospheric carbon dioxide.
AB  - Cenozoic temperature, sea level and CO2 covariations provide insights into
      climate sensitivity to external forcings and sea-level sensitivity to climate
      change. Climate sensitivity depends on the initial climate state, but potentially
      can be accurately inferred from precise palaeoclimate data. Pleistocene climate
      oscillations yield a fast-feedback climate sensitivity of 3+/-1( degrees )C for a
      4 W m(-2) CO2 forcing if Holocene warming relative to the Last Glacial Maximum
      (LGM) is used as calibration, but the error (uncertainty) is substantial and
      partly subjective because of poorly defined LGM global temperature and possible
      human influences in the Holocene. Glacial-to-interglacial climate change leading
      to the prior (Eemian) interglacial is less ambiguous and implies a sensitivity in
      the upper part of the above range, i.e. 3-4( degrees )C for a 4 W m(-2) CO2
      forcing. Slow feedbacks, especially change of ice sheet size and atmospheric CO2,
      amplify the total Earth system sensitivity by an amount that depends on the time
      scale considered. Ice sheet response time is poorly defined, but we show that the
      slow response and hysteresis in prevailing ice sheet models are exaggerated. We
      use a global model, simplified to essential processes, to investigate state
      dependence of climate sensitivity, finding an increased sensitivity towards
      warmer climates, as low cloud cover is diminished and increased water vapour
      elevates the tropopause. Burning all fossil fuels, we conclude, would make most
      of the planet uninhabitable by humans, thus calling into question strategies that
      emphasize adaptation to climate change. 

PMID- 24043865
TI  - On the identification of a Pliocene time slice for data-model comparison.
AB  - The characteristics of the mid-Pliocene warm period (mPWP: 3.264-3.025 Ma BP)
      have been examined using geological proxies and climate models. While there is
      agreement between models and data, details of regional climate differ.
      Uncertainties in prescribed forcings and in proxy data limit the utility of the
      interval to understand the dynamics of a warmer than present climate or evaluate
      models. This uncertainty comes, in part, from the reconstruction of a time slab
      rather than a time slice, where forcings required by climate models can be more
      adequately constrained. Here, we describe the rationale and approach for
      identifying a time slice(s) for Pliocene environmental reconstruction. A time
      slice centred on 3.205 Ma BP (3.204-3.207 Ma BP) has been identified as a
      priority for investigation. It is a warm interval characterized by a negative
      benthic oxygen isotope excursion (0.21-0.230/00) centred on marine isotope stage
      KM5c (KM5.3). It occurred during a period of orbital forcing that was very
      similar to present day. Climate model simulations indicate that proxy temperature
      estimates are unlikely to be significantly affected by orbital forcing for at
      least a precession cycle centred on the time slice, with the North Atlantic
      potentially being an important exception. 

PMID- 24043866
TI  - The PRISM (Pliocene palaeoclimate) reconstruction: time for a paradigm shift.
AB  - Global palaeoclimate reconstructions have been invaluable to our understanding of
      the causes and effects of climate change, but single-temperature representations
      of the oceanic mixed layer for data-model comparisons are outdated, and the time
      for a paradigm shift in marine palaeoclimate reconstruction is overdue. The new
      paradigm in marine palaeoclimate reconstruction stems the loss of valuable
      climate information and instead presents a holistic and nuanced interpretation of
      multi-dimensional oceanographic processes and responses. A wealth of
      environmental information is hidden within the US Geological Survey's Pliocene
      Research, Interpretation and Synoptic Mapping (PRISM) marine palaeoclimate
      reconstruction, and we introduce here a plan to incorporate all valuable climate
      data into the next generation of PRISM products. Beyond the global approach and
      focus, we plan to incorporate regional climate dynamics with emphasis on
      processes, integrating multiple environmental proxies wherever available in order
      to better characterize the mixed layer, and developing a finer time slice within
      the Mid-Piacenzian Age of the Pliocene, complemented by underused proxies that
      offer snapshots into environmental conditions. The result will be a proxy-rich,
      temporally nested, process-oriented approach in a digital format-a relational
      database with geographic information system capabilities comprising a three
      dimensional grid representing the surface layer, with a plethora of data in each
      cell. 

PMID- 24043867
TI  - Sensitivity of the Palaeocene-Eocene Thermal Maximum climate to cloud properties.
AB  - The Palaeocene-Eocene Thermal Maximum (PETM) was a significant global warming
      event in the Earth's history (approx. 55 Ma). The cause for this warming event
      has been linked to increases in greenhouse gases, specifically carbon dioxide and
      methane. This rapid warming took place in the presence of the existing Early
      Eocene warm climate. Given that projected business-as-usual levels of atmospheric
      carbon dioxide reach concentrations of 800-1100 ppmv by 2100, it is of interest
      to study past climates where atmospheric carbon dioxide was higher than present.
      This is especially the case given the difficulty of climate models in simulating
      past warm climates. This study explores the sensitivity of the simulated pre-PETM
      and PETM periods to change in cloud condensation nuclei (CCN) and microphysical
      properties of liquid water clouds. Assuming lower levels of CCN for both of these
      periods leads to significant warming, especially at high latitudes. The study
      indicates that past differences in cloud properties may be an important factor in
      accurately simulating past warm climates. Importantly, additional shortwave
      warming from such a mechanism would imply lower required atmospheric CO2
      concentrations for simulated surface temperatures to be in reasonable agreement
      with proxy data for the Eocene. 

PMID- 24043868
TI  - High-resolution alkenone palaeobarometry indicates relatively stable pCO(2)
      during the Pliocene (3.3-2.8 Ma).
AB  - Temperature reconstructions indicate that the Pliocene was approximately 3(
      degrees )C warmer globally than today, and several recent reconstructions of
      Pliocene atmospheric CO2 indicate that it was above pre-industrial levels and
      similar to those likely to be seen this century. However, many of these
      reconstructions have been of relatively low temporal resolution, meaning that
      these records may have failed to capture variations associated with the 41 kyr
      glacial-interglacial cycles thought to have operated in the Pliocene. Here we
      present a new, high temporal resolution alkenone carbon isotope-based record of
      pCO2 spanning 3.3-2.8 Ma from Ocean Drilling Program Site 999. Our record is of
      high enough resolution (approx. 19 kyr) to resolve glacial-interglacial changes
      beyond the intrinsic uncertainty of the proxy method. The record suggests that
      Pliocene CO2 levels were relatively stable, exhibiting variation less than 55
      ppm. We perform sensitivity studies to investigate the possible effect of
      changing sea surface temperature (SST), which highlights the importance of
      accurate and precise SST reconstructions for alkenone palaeobarometry, but
      demonstrate that these uncertainties do not affect our conclusions of relatively
      stable pCO2 levels during this interval. 

PMID- 24043869
TI  - A 40-million-year history of atmospheric CO(2).
AB  - The alkenone-pCO2 methodology has been used to reconstruct the partial pressure
      of ancient atmospheric carbon dioxide (pCO2) for the past 45 million years of
      Earth's history (Middle Eocene to Pleistocene epochs). The present long-term CO2
      record is a composite of data from multiple ocean localities that express a wide
      range of oceanographic and algal growth conditions that potentially bias CO2
      results. In this study, we present a pCO2 record spanning the past 40 million
      years from a single marine locality, Ocean Drilling Program Site 925 located in
      the western equatorial Atlantic Ocean. The trends and absolute values of our new
      CO2 record site are broadly consistent with previously published multi-site
      alkenone-CO2 results. However, new pCO2 estimates for the Middle Miocene are
      notably higher than published records, with average pCO2 concentrations in the
      range of 400-500 ppm. Our results are generally consistent with recent pCO2
      estimates based on boron isotope-pH data and stomatal index records, and suggest
      that CO2 levels were highest during a period of global warmth associated with the
      Middle Miocene Climatic Optimum (17-14 million years ago, Ma), followed by a
      decline in CO2 during the Middle Miocene Climate Transition (approx. 14 Ma).
      Several relationships remain contrary to expectations. For example, benthic
      foraminiferal delta(18)O records suggest a period of deglaciation and/or high
      latitude warming during the latest Oligocene (27-23 Ma) that, based on our
      results, occurred concurrently with a long-term decrease in CO2 levels.
      Additionally, a large positive delta(18)O excursion near the Oligocene-Miocene
      boundary (the Mi-1 event, approx. 23 Ma), assumed to represent a period of
      glacial advance and retreat on Antarctica, is difficult to explain by our CO2
      record alone given what is known of Antarctic ice sheet history and the strong
      hysteresis of the East Antarctic Ice Sheet once it has grown to continental
      dimensions. We also demonstrate that in the Neogene with low CO2 levels, algal
      carbon concentrating mechanisms and spontaneous biocarbonate-CO2 conversions are
      likely to play a more important role in algal carbon fixation, which provides a
      potential bias to the alkenone-pCO2 method. 

PMID- 24043870
TI  - How warm was the last interglacial? New model-data comparisons.
AB  - A Community Climate System Model, Version 3 (CCSM3) simulation for 125 ka during
      the Last Interglacial (LIG) is compared to two recent proxy reconstructions to
      evaluate surface temperature changes from modern times. The dominant forcing
      change from modern, the orbital forcing, modified the incoming solar insolation
      at the top of the atmosphere, resulting in large positive anomalies in boreal
      summer. Greenhouse gas concentrations are similar to those of the pre-industrial
      (PI) Holocene. CCSM3 simulates an enhanced seasonal cycle over the Northern
      Hemisphere continents with warming most developed during boreal summer. In
      addition, year-round warming over the North Atlantic is associated with a
      seasonal memory of sea ice retreat in CCSM3, which extends the effects of
      positive summer insolation anomalies on the high-latitude oceans to winter
      months. The simulated Arctic terrestrial annual warming, though, is much less
      than the observational evidence, suggesting either missing feedbacks in the
      simulation and/or interpretation of the proxies. Over Antarctica, CCSM3 cannot
      reproduce the large LIG warming recorded by the Antarctic ice cores, even with
      simulations designed to consider observed evidence of early LIG warmth in
      Southern Ocean and Antarctica records and the possible disintegration of the West
      Antarctic Ice Sheet. Comparisons with a HadCM3 simulation indicate that sea ice
      is important for understanding model polar responses. Overall, the models
      simulate little global annual surface temperature change, while the proxy
      reconstructions suggest a global annual warming at LIG (as compared to the PI
      Holocene) of approximately 1( degrees )C, though with possible spatial sampling
      biases. The CCSM3 SRES B1 (low scenario) future projections suggest high-latitude
      warmth similar to that reconstructed for the LIG may be exceeded before the end
      of this century. 

PMID- 24043871
TI  - Warm ocean processes and carbon cycling in the Eocene.
AB  - Sea surface and subsurface temperatures over large parts of the ocean during the
      Eocene epoch (55.5-33.7 Ma) exceeded modern values by several degrees, which must
      have affected a number of oceanic processes. Here, we focus on the effect of
      elevated water column temperatures on the efficiency of the biological pump,
      particularly in relation to carbon and nutrient cycling. We use stable isotope
      values from exceptionally well-preserved planktonic foraminiferal calcite from
      Tanzania and Mexico to reconstruct vertical carbon isotope gradients in the upper
      water column, exploiting the fact that individual species lived and calcified at
      different depths. The oxygen isotope ratios of different species' tests are used
      to estimate the temperature of calcification, which we converted to absolute
      depths using Eocene temperature profiles generated by general circulation models.
      This approach, along with potential pitfalls, is illustrated using data from
      modern core-top assemblages from the same area. Our results indicate that, during
      the Early and Middle Eocene, carbon isotope gradients were steeper (and larger)
      through the upper thermocline than in the modern ocean. This is consistent with a
      shallower average depth of organic matter remineralization and supports
      previously proposed hypotheses that invoke high metabolic rates in a warm Eocene
      ocean, leading to more efficient recycling of organic matter and reduced burial
      rates of organic carbon. 

PMID- 24043872
TI  - The Early Eocene equable climate problem: can perturbations of climate model
      parameters identify possible solutions?
AB  - Geological data for the Early Eocene (56-47.8 Ma) indicate extensive global
      warming, with very warm temperatures at both poles. However, despite numerous
      attempts to simulate this warmth, there are remarkable data-model differences in
      the prediction of these polar surface temperatures, resulting in the so-called
      'equable climate problem'. In this paper, for the first time an ensemble with a
      perturbed climate-sensitive model parameters approach has been applied to
      modelling the Early Eocene climate. We performed more than 100 simulations with
      perturbed physics parameters, and identified two simulations that have an optimal
      fit with the proxy data. We have simulated the warmth of the Early Eocene at 560
      ppmv CO2, which is a much lower CO2 level than many other models. We investigate
      the changes in atmospheric circulation, cloud properties and ocean circulation
      that are common to these simulations and how they differ from the remaining
      simulations in order to understand what mechanisms contribute to the polar
      warming. The parameter set from one of the optimal Early Eocene simulations also
      produces a favourable fit for the last glacial maximum boundary climate and
      outperforms the control parameter set for the present day. Although this does not
      'prove' that this model is correct, it is very encouraging that there is a
      parameter set that creates a climate model able to simulate well very different
      palaeoclimates and the present-day climate. Interestingly, to achieve the great
      warmth of the Early Eocene this version of the model does not have a strong
      future climate change Charney climate sensitivity. It produces a Charney climate
      sensitivity of 2.7( degrees )C, whereas the mean value of the 18 models in the
      IPCC Fourth Assessment Report (AR4) is 3.26( degrees )C+/-0.69( degrees )C. Thus,
      this value is within the range and below the mean of the models included in the
      AR4. 

PMID- 24043873
TI  - Warm climates of the past--a lesson for the future?
AB  - This Discussion Meeting Issue of the Philosophical Transactions A had its genesis
      in a Discussion Meeting of the Royal Society which took place on 10-11 October
      2011. The Discussion Meeting, entitled 'Warm climates of the past: a lesson for
      the future?', brought together 16 eminent international speakers from the field
      of palaeoclimate, and was attended by over 280 scientists and members of the
      public. Many of the speakers have contributed to the papers compiled in this
      Discussion Meeting Issue. The papers summarize the talks at the meeting, and
      present further or related work. This Discussion Meeting Issue asks to what
      extent information gleaned from the study of past climates can aid our
      understanding of future climate change. Climate change is currently an issue at
      the forefront of environmental science, and also has important sociological and
      political implications. Most future predictions are carried out by complex
      numerical models; however, these models cannot be rigorously tested for scenarios
      outside of the modern, without making use of past climate data. Furthermore, past
      climate data can inform our understanding of how the Earth system operates, and
      can provide important contextual information related to environmental change. All
      past time periods can be useful in this context; here, we focus on past climates
      that were warmer than the modern climate, as these are likely to be the most
      similar to the future. This introductory paper is not meant as a comprehensive
      overview of all work in this field. Instead, it gives an introduction to the
      important issues therein, using the papers in this Discussion Meeting Issue, and
      other works from all the Discussion Meeting speakers, as exemplars of the various
      ways in which past climates can inform projections of future climate.
      Furthermore, we present new work that uses a palaeo constraint to quantitatively
      inform projections of future equilibrium ice sheet change. 

PMID- 24043874
TI  - A comparative study of the peripheral doses from a linear accelerator with a
      multileaf collimator system.
AB  - This study presents a comparison of peripheral doses (PDs) measured using an
      ionisation chamber with treatment planning system (TPS) data and a Monte Carlo
      (MC) simulation of a 6-MV photon beam. The ion chamber measurements and MC
      simulation produced similar results for all out-of-field distances and field
      sizes considered in this study. For the 0 degrees  and 90 degrees  collimation
      angles, the average local per cent dose differences between the MC and TPS
      calculations were 2.7 % (range: -2.4, +22.6) and -1.7 % (range: -12.2, +10.8),
      respectively. The corresponding differences between the MC calculations and the
      ion chamber measurements were 2.2 % (range: -2.4, 24.7) and -1.8 % (range: -17,
      15.2) for all field sizes and depths, respectively. Whereas the PDs increased
      with field sizes, the variations with depth were negligible at large distances.
      The TPS calculations usually yielded higher PDs than ion chamber measurements at
      distances close to the field edge. In contrast, at the farther distances, the TPS
      results indicated lower doses than both the ion chamber and the MC data. TPS data
      are not sufficient for use in calculating the out-of-field doses. These results
      can be used to estimate non-target organ doses to patients. 

PMID- 24043875
TI  - The establishment of computed tomography diagnostic reference levels in Portugal.
AB  - The aims of this study were to investigate the frequency of Portuguese computed
      tomography (CT) examinations, identify protocol application and establish
      diagnostic reference levels (DRLs). CT departments (n=211) were surveyed
      nationally (June 2011-January 2012) and CT protocol information and dose data
      were collected, as were retrospective age-categorised paediatric CT data from
      three national paediatric centres. The proposed national CT DRLs (CTDIvol) for
      adults were 75, 18, 14, 18, 17, 36, 22, 27 and 16 mGy for head, neck, chest,
      abdomen, pelvis, cervical, dorsal, lumbar and joints, respectively. The levels
      for paediatric head and chest examinations were as follows: 48 and 2 mGy
      (newborns), 50 and 6 mGy (5 y olds), 70 and 6 mGy (10 y olds) and 72 and 7 mGy
      (15 y olds). A limited number of current paediatric protocols aligned to
      recommended international age categorisations. Portuguese DRLs were generally
      higher than European recommendations, suggesting potential for optimisation. The
      need for greater standardisation of age-categorised paediatric protocols was
      identified. 

PMID- 24043876
TI  - Very-low-frequency and low-frequency electric and magnetic fields associated with
      electric shuttle bus wireless charging.
AB  - Tests conducted to date at the University of Tennessee at Chattanooga (UTC)
      indicate that wireless charging of the Chattanooga Area Regional Transportation
      Authority's (CARTA) downtown shuttle bus, currently operating with off-board
      battery charging technology, offers significant improvements in performance and
      cost. The system operates at a frequency of 20 kHz and a peak power of 60 kW.
      Because the system's wireless charging is expected to occur during a nominal 3
      min charging period with passengers on-board, the magnetic and electric fields
      associated with charging were characterised at UTC's Advanced Vehicle Test
      Facility and compared with established human exposure limits. The two most
      prominent exposure limits are those published by the International Commission on
      Non-Ionizing Radiation Protection (ICNIRP) and the Institute for Electrical and
      Electronic Engineers (IEEE). Both organisations include limits for groups who are
      trained (workers in specific industries) to be aware of electromagnetic
      environments and their potential hazards, as well as a lower set of limits for
      the general public, who are assumed to lack such awareness. None of the magnetic
      or electric fields measured either within or outside the bus during charging
      exceeded either the ICNIRP or the IEEE exposure limits for the general public. 

PMID- 24043877
TI  - Dosimetric evaluation of dental implant planning examinations with cone-beam
      computed tomography.
AB  - The aim of this work was to perform a dosimetric evaluation of two cone-beam
      computed tomography scanners. The study was performed with two scanners: i-CAT
      classic and PreXion 3D. Air kerma-area product (PKA) was measured for all full
      arch dental implant planning protocols. Surface air kerma was also estimated at
      the region of the eyes, salivary glands and thyroid using thermoluminescence
      dosemeters positioned on an anthropomorphic phantom. The PKA values for the i-CAT
      classic ranged from 24 to 180 uGy m(2) and, for the PreXion, from 70 to 138 uGy
      m(2). The large variation of these values was mainly caused by acquisition time
      and field of views. The surface air kerma values were from 0.08 to 3.39 mGy at
      the eyes, 0.50 to 3.96 mGy at the parotids, 0.11 to 2.95 mGy at the submandibular
      glands and 0.05 to 1.32 mGy at the thyroid. These values are comparable with
      those found in the literature. 

PMID- 24043879
TI  - Effect of surgery on periventricular white matter in normal pressure
      hydrocephalus patients: comparison of two methods of DTI analysis.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) is a useful tool for assessing changes
      that occur in microstructures. We have developed a novel method for region of
      interest (ROI) delineation in the assessment of DTI parameters in patients with
      normal pressure hydrocephalus (NPH). PURPOSE: To compare the standard method and
      our novel method in an evaluation of the impact of surgery on periventricular
      white matter in patients with NPH. MATERIAL AND METHODS: Ten patients with NPH
      underwent 3T magnetic resonance imaging (MRI; including 12-direction DTI
      sequences) before and after surgery. We recorded diffusion parameters (lambdai,
      the fractional anisotropy [FA], the apparent diffusion coefficient, and Dr) in
      the internal capsule (IC) and the body of the corpus callosum (BCC). Using the
      standard delineation technique, regions of interest (ROIs) were positioned
      according to anatomical and functional considerations and then filled with
      several sub-ROIs. The ROIs delineated with our novel technique (extracted as the
      six sub-ROIs with the lowest standard deviation for the FA) were arranged in two
      rows (medial and lateral), from the ventricle to the brain surface. RESULTS: The
      within-ROI homogeneity was higher with the novel method than with the
      conventional method (P<10(-4)). When the conventional delineation method was
      applied to the IC data, only lambda2 was found to be significantly greater after
      surgery; in contrast, application of our novel method evidenced a significant
      decrease in FA and lambda1 and a significant increase in lambda2 (P<0.05). Both
      before and after surgery, the FA in the medial row of ROIs was greater than the
      FA in the lateral row (P<0.01). In the BCC, only lambda2 and Dr varied
      significantly (when evaluated with the novel method). CONCLUSION: Our results
      show that use of a novel method of DTI data analysis may be more sensitive to
      local changes induced by surgical procedures. Furthermore, this novel method was
      able to detect the transmantle pressure gradient related to the regional stress
      distribution.

PMID- 24043878
TI  - Common variants on Xq28 conferring risk of schizophrenia in Han Chinese.
AB  - Schizophrenia is a highly heritable, severe psychiatric disorder affecting
      approximately 1% of the world population. A substantial portion of heritability
      is still unexplained and the pathophysiology of schizophrenia remains to be
      elucidated. To identify more schizophrenia susceptibility loci, we performed a
      genome-wide association study (GWAS) on 498 patients with schizophrenia and 2025
      controls from the Han Chinese population, and a follow-up study on 1027 cases and
      1005 controls. In the follow-up study, we included 384 single nucleotide
      polymorphisms (SNPs) which were selected from the top hits in our GWAS (130 SNPs)
      and from previously implicated loci for schizophrenia based on the SZGene
      database, NHGRI GWAS Catalog, copy number variation studies, GWAS meta-analysis
      results from the international Psychiatric Genomics Consortium (PGC) and
      candidate genes from plausible biological pathways (254 SNPs). Within the
      chromosomal region Xq28, SNP rs2269372 in RENBP achieved genome-wide significance
      with a combined P value of 3.98 * 10(-8) (OR of allele A = 1.31). SNPs with
      suggestive P values were identified within 2 genes that have been previously
      implicated in schizophrenia, MECP2 (rs2734647, P combined = 8.78 * 10(-7), OR =
      1.28; rs2239464, P combined = 6.71 * 10(-6), OR = 1.26) and ARHGAP4 (rs2269368, P
      combined = 4.74 * 10(-7), OR = 1.25). In addition, the patient sample in our
      follow-up study showed a significantly greater burden for pre-defined risk
      alleles based on the SNPs selected than the controls. This indicates the
      existence of schizophrenia susceptibility loci among the SNPs we selected. This
      also further supports multigenic inheritance in schizophrenia. Our findings
      identified a new schizophrenia susceptibility locus on Xq28, which harbor the
      genes RENBP, MECP2, and ARHGAP4.

PMID- 24043880
TI  - Safety and tolerability of iopromide intravascular use: a pooled analysis of
      three non-interventional studies in 132,012 patients.
AB  - BACKGROUND: Determining the safety of contrast agents is challenging. In the
      absence of large controlled clinical trials, non-interventional (post-marketing
      surveillance) studies provide an opportunity to clearly investigate the safety
      profile of contrast agents. PURPOSE: To assess the safety profile of iopromide in
      contrast-enhanced X-ray in clinical practice, using pooled data from three non
      interventional studies. MATERIAL AND METHODS: All studies were international,
      multicenter, non-interventional studies examining iopromide tolerability in
      clinical practice. Patients received iopromide (iodine concentrations of 300
      mg/mL or 370 mg/mL) via intravenous or intra-arterial administration according to
      the diagnostic indication and in compliance with the local package insert.
      RESULTS: In total, 132,012 patients (37 countries, >1600 centers) were included.
      Overall, 3823 patients (2.49%) reported an adverse drug reaction (ADR) and 1983
      patients (1.50%) reported an ADR without tolerance indicators (injection site
      warmth, feeling hot or injection site pain, of mild intensity only). This is a
      similar rate to other low osmolar contrast media. In most patients, ADRs were
      mild (n = 2632; 1.99% of all patients) and did not require any action (n = 2799;
      2.12% of all patients). ADRs were more common among women (n = 1680 [2.8%]) than
      men (n = 1586 [2.2%]) and among younger patients (<18 years: n = 98 [3.2%]) than
      older patients (18-49 years: n = 1261 [3.5%]; 50-69 years: n = 1224 [2.2%]; >=70
      years: n = 362 [1.5%]). The most common ADRs were injection site warmth/feeling
      hot, nausea/vomiting, and dysguesia. Forty-five serious ADRs were reported in 19
      patients. ADRs were more common in at-risk patients (5.00%) than in the overall
      population. CONCLUSION: This pooled analysis confirms the well-established good
      safety profile of iopromide in clinical practice in Asian and European countries
      and the USA.

PMID- 24043881
TI  - The diagnostic sensitivity of dynamic contrast-enhanced magnetic resonance
      imaging and breast-specific gamma imaging in women with calcified and non
      calcified DCIS.
AB  - BACKGROUND: Early detection of breast cancer reduces mortality. Therefore,
      diagnosis of ductal carcinoma in situ (DCIS) is important. PURPOSE: To compare
      the sensitivities of dynamic contrast-enhanced magnetic resonance imaging (DCE
      MRI) and breast-specific gamma imaging (BSGI) in pathologically proven calcified
      and non-calcified DCIS. MATERIAL AND METHODS: Thirty-five patients with
      pathologically diagnosed DCIS from 1 June 2009 through 31 December 2011,
      underwent a protocol involving both breast MRI and BSGI. Each image was assessed
      by a separate dedicated breast radiologist. All lesions were divided into two
      groups; with or without microcalcifications on mammograms. In cases without
      microcalcifications, we recorded the mass, asymmetry, or negative findings on
      mammography. On MRI, the enhancement pattern was categorized as mass or non-mass
      like enhancement. On BSGI, the uptake pattern was analyzed. The histopathological
      features of the lesions were obtained. Statistical analysis of the sensitivity of
      each modality was performed using McNemar's test. RESULTS: Thirty-five women with
      a mean age of 48 years (range, 26-69 years) were enrolled in the study. The total
      sensitivities of MRI and BSGI in the 35 cases were 91.4% (32 of 35 DCIS) and
      68.6% (24 of 35 DCIS), respectively. Eighteen cases with DCIS displayed
      microcalcifications on mammography, while 17 cases did not. Of these 17 cases
      without microcalcifications on mammography, 88.2% (15 of 17 DCIS) were detected
      by MRI and 52.9% (9 of 17 DCIS) by BSGI. Of 18 cases with microcalcifications on
      mammography, 94.4% (17 of 18 DCIS) were detected by MRI and 83.3% (15 of 19 DCIS)
      by BSGI. CONCLUSION: MRI showed a higher sensitivity for the detection of
      calcified and non-calcified DCIS and is more helpful than BSGI in cases without
      microcalcifications on mammography.

PMID- 24043882
TI  - Diffusion tensor imaging of cysts, hemangiomas, and metastases of the liver.
AB  - BACKGROUND: Although diffusion-weighted magnetic resonance imaging imaging (DW
      MRI) is commonly used to characterize hepatic lesions, the literature is sparse
      about the use of MR diffusion tensor imaging (DTI) in this regard. By using DTI,
      one is able to obtain not only apparent diffusion coefficients (ADCs) but also
      fractional anisotropy (Fa) values. PURPOSE: To evaluate DTI using ADC and Fa
      values in the imaging of hepatic cysts, hemangiomas, and metastases. MATERIAL AND
      METHODS: Sixty-six patients with 77 lesions were examined with DTI. There were 32
      metastases, 13 cysts, and 32 hemangiomas. Two radiologists performed ADC and Fa
      measurements. Inter-observer agreement was evaluated using Bland-Altman plots.
      ADCs and Fa values were correlated using Pearson correlation. The differences
      were compared using ANOVA and Tukey tests. A ROC analysis was applied;
      sensitivities and specificities were calculated. RESULTS: The inter-observer
      agreement was very good. The correlation between ADC and Fa was negative, weak,
      and significant (r = -0.36). The mean ADC value of cysts (3.30 +/- 0.8 * 10(-3)
      mm(2)/s) was significantly higher than that of hemangiomas (2.23 +/- 0.5 * 10(-3)
      mm(2)/s) and metastases (1.62 +/- 0.4 * 10(-3) mm(2)/s). The mean Fa value of
      cysts (0.2 +/- 0.05) was significantly lower than hemangiomas (0.37 +/- 0.1) and
      metastases (0.46 +/- 0.1). The Az values for discriminating metastases from
      benign hepatic lesions for ADC and Fa value were 0.885 and 0.731, respectively.
      The sensitivity and specificity of ADC and Fa were 87.5% and 84.4%, and 78.1% and
      57.8%, respectively. The Az value for discriminating cysts from hemangiomas for
      Fa was 0.96. The sensitivity and specificity were 90.6% and 92.3%, respectively.
      CONCLUSION: Fa values may play a supportive role in the imaging of liver lesions.
      Whereas metastases tend to have low ADCs and high Fa values, cysts have high ADCs
      and low Fa values and hemangiomas have high ADCs and high Fa values.

PMID- 24043883
TI  - Prospective clarification of the utility of the palliative prognostic index for
      patients with advanced cancer in the home care setting.
AB  - AIMS: This study aimed to prospectively clarify the accuracy of the Palliative
      Prognostic Index (PPI) for advanced cancer patients in home care settings.
      METHOD: The study included 66 advanced cancer patients who received home visiting
      services between April 2010 and June 2012, and who died at home or in the
      hospital. Using medical records from initial home visits, we prospectively
      calculated PPI scores along with sensitivity and specificity. RESULTS: For 3- and
      6-week survival, prognostic prediction showed respective sensitivities of 60% and
      70.6%, and specificities of 87.0% and 71.9%. CONCLUSION: The sensitivity of the
      PPI for advanced cancer patients in home care settings was lower than that
      reported for patients in palliative care units. Development of prognostic tools
      suitable for home care settings is needed.

PMID- 24043884
TI  - The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus.
AB  - We investigated the roles of IFN regulatory factor (IRF)-3 and IRF-7 in innate
      antiviral immunity against dengue virus (DENV). Double-deficient Irf-3(-/-)7(-/-)
      mice infected with the DENV2 strain S221 possessed 1,000-150,000 fold higher
      levels of viral RNA than wild-type and single-deficient mice 24 h postinfection
      (hpi); however, they remained resistant to lethal infection. IFN-alpha/beta was
      induced similarly in wild-type and Irf-3(-/-) mice post-DENV infection, whereas
      in the Irf-7(-/-) and Irf-3(-/-)7(-/-) mice, significantly low levels of IFN
      alpha/beta expression was observed within 24 hpi. IFN-stimulated gene induction
      was also delayed in Irf-3(-/-)7(-/-) mice relative to wild-type and single
      deficient mice. In particular, Cxcl10 and Ifnalpha2 were rapidly induced
      independently of both IRF-3 and IRF-7 in the Irf-3(-/-)7(-/-) mice with DENV
      infection. Higher levels of serum IFN-gamma, IL-6, CXCL10, IL-8, IL-12 p70, and
      TNF were also observed in Irf-3(-/-)7(-/-) mice 24 hpi, at which time point viral
      titers peaked and started to be cleared. Ab-mediated blockade experiments
      revealed that IFN-gamma, CXCL10, and CXCR3 function to restrict DENV replication
      in Irf-3(-/-)7(-/-) mice. Additionally, the IFN-stimulated genes Cxcl10, Ifit1,
      Ifit3, and Mx2 can be induced via an IRF-3- and IRF-7-independent pathway that
      does not involve IFN-gamma signaling for protection against DENV. Collectively,
      these results demonstrate that IRF-3 and IRF-7 are redundant, albeit IRF-7 plays
      a more important role than IRF-3 in inducing the initial IFN-alpha/beta response;
      only the combined actions of IRF-3 and IRF-7 are necessary for efficient control
      of early DENV infection; and the late, IRF-3- and IRF-7-independent pathway
      contributes to anti-DENV immunity.

PMID- 24043886
TI  - HIV-1 gp120 induces TLR2- and TLR4-mediated innate immune activation in human
      female genital epithelium.
AB  - Although women constitute half of all HIV-1-infected people worldwide (UNAIDS
      World AIDS Day Report, 2011), the earliest events in the female reproductive
      tract (FRT) during heterosexual HIV-1 transmission are poorly understood.
      Recently, we demonstrated that HIV-1 could directly impair the mucosal epithelial
      barrier in the FRT. This suggested that the HIV-1 envelope glycoprotein gp120 was
      being recognized by a membrane receptor on genital epithelial cells, leading to
      innate immune activation. In this study, we report that pattern-recognition
      receptors TLR2 and -4 bind to HIV-1 gp120 and trigger proinflammatory cytokine
      production via activation of NF-kappaB. The gp120-TLR interaction also required
      the presence of heparan sulfate (HS). Bead-binding assays showed that gp120 can
      bind to HS, TLR2, and TLR4, and studies in transfected HEK293 cells demonstrated
      that HS and TLR2 and -4 were necessary to mediate downstream signaling. Exposure
      to seminal plasma from HIV-1-infected and uninfected men with gp120 added to it
      induced a significant proinflammatory cytokine response from genital epithelial
      cells and disruption of tight junctions, indicating a role for gp120 in mucosal
      barrier disruption during HIV-1 heterosexual transmission. These studies provide,
      for the first time to our knowledge, a possible mechanism by which HIV-1 gp120
      could directly initiate innate immune activation in the FRT during heterosexual
      transmission. 

PMID- 24043885
TI  - Inflammasome-mediated secretion of IL-1beta in human monocytes through TLR2
      activation; modulation by dietary fatty acids.
AB  - Many studies have shown that TLR4- and TLR2-deficient mice are protected from
      high-fat diet-induced inflammation and insulin resistance, suggesting that
      saturated fatty acids derived from the high-fat diet activate TLR-mediated
      proinflammatory signaling pathways and induce insulin resistance. However,
      evidence that palmitic acid, the major dietary saturated fatty acid, can directly
      activate TLR has not been demonstrated. In this article, we present multiple
      lines of evidence showing that palmitic acid directly activates TLR2, a major TLR
      expressed on human monocytes, by inducing heterodimerization with TLR1 in an
      NADPH oxidase-dependent manner. Dimerization of TLR2 with TLR1 was inhibited by
      the n-3 fatty acid docosahexaenoic acid. Activation of TLR2 by palmitic acid
      leads to expression of pro-IL-1beta that is cleaved by caspase-1, which is
      constitutively present in monocytes, to release mature IL-1beta. Our results
      reveal mechanistic insight about how palmitic acid activates TLR2, upregulates
      NALP3 expression, and induces inflammasome-mediated IL-1beta production in human
      monocytes, which can trigger enhanced inflammation in peripheral tissues, and
      suggest that these processes are dynamically modulated by the types of dietary
      fat we consume. 

PMID- 24043887
TI  - The complement anaphylatoxin C5a receptor contributes to obese adipose tissue
      inflammation and insulin resistance.
AB  - Obese adipose tissue (AT) inflammation contributes critically to development of
      insulin resistance. The complement anaphylatoxin C5a receptor (C5aR) has been
      implicated in inflammatory processes and as regulator of macrophage activation
      and polarization. However, the role of C5aR in obesity and AT inflammation has
      not been addressed. We engaged the model of diet-induced obesity and found that
      expression of C5aR was significantly upregulated in the obese AT, compared with
      lean AT. In addition, C5a was present in obese AT in the proximity of macrophage
      rich crownlike structures. C5aR-sufficient and -deficient mice were fed a high
      fat diet (HFD) or a normal diet (ND). C5aR deficiency was associated with
      increased AT weight upon ND feeding in males, but not in females, and with
      increased adipocyte size upon ND and HFD conditions in males. However, obese
      C5aR(-/-) mice displayed improved systemic and AT insulin sensitivity. Improved
      AT insulin sensitivity in C5aR(-/-) mice was associated with reduced accumulation
      of total and proinflammatory M1 macrophages in the obese AT, increased expression
      of IL-10, and decreased AT fibrosis. In contrast, no difference in beta cell mass
      was observed owing to C5aR deficiency under an HFD. These results suggest that
      C5aR contributes to macrophage accumulation and M1 polarization in the obese AT
      and thereby to AT dysfunction and development of AT insulin resistance. 

PMID- 24043888
TI  - Disruption of the complement anaphylatoxin receptor C5L2 exacerbates inflammation
      in allergic contact dermatitis.
AB  - The complement anaphylatoxin C5a is a critical mediator of allergic contact
      dermatitis, bridging essential aspects of innate and adaptive immunity. This
      anaphylatoxin functions by interacting with two 7-transmembrane segment
      receptors, the C5aR and C5L2. The C5aR is a classical G protein coupled receptor,
      whereas C5L2 is deficient in coupling to G proteins because of variations in the
      sequence. Our previous work in human neutrophils revealed a unique role for C5L2
      in negatively modulating anaphylatoxin receptor mediated cellular activation
      through interactions with beta-arrestin. When C5L2 is deficient, C5aR-mediated
      beta-arrestin signaling is greatly enhanced. The work described in this study was
      undertaken first to determine the effect of C5L2 deficiency in a murine model of
      contact sensitivity, and second to determine whether the resultant exacerbation
      of inflammatory parameters reflects a negative modulatory function of C5L2 on the
      C5aR. First, we find dramatic increases in inflammation in C5L2(-/-) animals
      compared with wild type mice. Second, these increases are completely reversed
      following administration of mAb against the C5aR. Thus, in allergic contact
      sensitivity, as in isolated human neutrophils, C5L2 functions to suppress C5a
      C5aR-mediated responses, further underscoring its role as a negative regulator of
      anaphylatoxin activity. 

PMID- 24043889
TI  - Inflammatory responses induced by lipopolysaccharide are amplified in primary
      human monocytes but suppressed in macrophages by complement protein C5a.
AB  - Monocytes and macrophages are important innate immune cells equipped with danger
      sensing receptors, including complement and Toll-like receptors. Complement
      protein C5a, acting via C5aR, is shown in this study to differentially modulate
      LPS-induced inflammatory responses in primary human monocytes versus macrophages.
      Whereas C5a enhanced secretion of LPS-induced IL-6 and TNF from primary human
      monocytes, C5a inhibited these responses while increasing IL-10 secretion in
      donor-matched human monocyte-derived macrophages differentiated by GM-CSF or M
      CSF. Galphai/c-Raf/MEK/ERK signaling induced by C5a was amplified in macrophages
      but not in monocytes by LPS. Accordingly, the Galphai inhibitor pertussis toxin
      and MEK inhibitor U0126 blocked C5a inhibition of LPS-induced IL-6 and TNF
      production from macrophages. This synergy was independent of IL-10, PI3K, p38,
      JNK, and the differentiating agent. Furthermore, C5a did not inhibit IL-6
      production from macrophages induced by other TLR agonists that are selective for
      Toll/IL-1R domain-containing adapter inducing IFN-beta (polyinosinic
      polycytidylic acid) or MyD88 (imiquimod), demonstrating selectivity for C5a
      regulation of LPS responses. Finally, suppression of proinflammatory cytokines IL
      6 and TNF in macrophages did not compromise antimicrobial activity; instead, C5a
      enhanced clearance of the Gram-negative bacterial pathogen Salmonella enterica
      serovar Typhimurium from macrophages. C5aR is thus a regulatory switch that
      modulates TLR4 signaling via the Galphai/c-Raf/MEK/ERK signaling axis in human
      macrophages but not monocytes. The differential effects of C5a are consistent
      with amplifying monocyte proinflammatory responses to systemic danger signals,
      but attenuating macrophage cytokine responses (without compromising microbicidal
      activity), thereby restraining inflammatory responses to localized infections. 

PMID- 24043890
TI  - Ezrin tunes the magnitude of humoral immunity.
AB  - Ezrin is a member of the ezrin-radixin-moesin family of membrane-actin
      cytoskeleton cross-linkers that participate in a variety of cellular processes.
      In B cells, phosphorylation of ezrin at different sites regulates multiple
      processes, such as lipid raft coalescence, BCR diffusion, microclustering, and
      endosomal JNK activation. In this study, we generated mice with conditional
      deletion of ezrin in the B cell lineage to investigate the physiological
      significance of ezrin's function in Ag receptor-mediated B cell activation and
      humoral immunity. B cell development, as well as the proportion and numbers of
      major B cell subsets in peripheral lymphoid organs, was unaffected by the loss of
      ezrin. Using superresolution imaging methods, we show that, in the absence of
      ezrin, BCRs respond to Ag binding by accumulating into larger and more stable
      signaling microclusters. Loss of ezrin led to delayed BCR capping and accelerated
      lipid raft coalescence. Although proximal signaling proteins showed stronger
      activation in the absence of ezrin, components of the distal BCR signaling
      pathways displayed distinct effects. Ezrin deficiency resulted in increased B
      cell proliferation and differentiation into Ab-secreting cells ex vivo and
      stronger T cell-independent and -dependent responses to Ag in vivo. Overall, our
      data demonstrate that ezrin regulates amplification of BCR signals and tunes the
      strength of B cell activation and humoral immunity. 

PMID- 24043891
TI  - Adenovirus-based vaccine against Listeria monocytogenes: extending the concept of
      invariant chain linkage.
AB  - The use of replication-deficient adenoviruses as vehicles for transfer of foreign
      genes offers many advantages in a vaccine setting, eliciting strong cellular
      immune responses involving both CD8(+) and CD4(+) T cells. Further improving the
      immunogenicity, tethering of the inserted target Ag to MHC class II-associated
      invariant chain (Ii) greatly enhances both the presentation of most target Ags,
      as well as overall protection against viral infection, such as lymphocytic
      choriomeningitis virus (LCMV). The present study extends this vaccination concept
      to include protection against intracellular bacteria, using Listeria
      monocytogenes as a model organism. Protection in C57BL/6 mice against recombinant
      L. monocytogenes expressing an immunodominant epitope of the LCMV glycoprotein
      (GP33) was greatly accelerated, augmented, and prolonged following vaccination
      with an adenoviral vaccine encoding GP linked to Ii compared with vaccination
      with the unlinked vaccine. Studies using knockout mice demonstrated that CD8(+) T
      cells were largely responsible for this protection, which is mediated through
      perforin-dependent lysis of infected cells and IFN-gamma production. Taking the
      concept a step further, vaccination of C57BL/6 (L. monocytogenes-resistant) and
      BALB/c (L. monocytogenes-susceptible) mice with adenoviral vectors encoding
      natural L. monocytogenes-derived soluble Ags (listeriolysin O and p60) revealed
      that tethering of these Ags to Ii markedly improved the vaccine-induced CD8(+) T
      cell response to two of three epitopes studied. More importantly, Ii linkage
      accelerated and augmented vaccine-induced protection in both mouse strains and
      prolonged protection, in particular that induced by the weak Ag, p60, in L.
      monocytogenes-susceptible BALB/c mice. 

PMID- 24043892
TI  - Cutting edge: TLR signaling licenses IRAK1 for rapid activation of the NLRP3
      inflammasome.
AB  - Activation of the NLRP3 inflammasome by diverse stimuli requires a priming signal
      from TLRs and an activation signal from purinergic receptors or pore-forming
      toxins. In this study, we demonstrate, through detailed analysis of NLRP3
      activation in macrophages deficient in key downstream TLR signaling molecules,
      that MyD88 is required for an immediate early phase, whereas Toll/IL-1R domain
      containing adapter inducing IFN-beta is required for a subsequent intermediate
      phase of posttranslational NLRP3 activation. Both IL-1R-associated kinase (IRAK)
      1 and IRAK4 are critical for rapid activation of NLRP3 through the MyD88 pathway,
      but only IRAK1 is partially required in the Toll/IL-1R domain-containing adapter
      inducing IFN-beta pathway. IRAK1 and IRAK4 are also required for rapid activation
      of NLRP3 by Listeria monocytogenes, as deletion of IRAK1 or IRAK4 led to
      defective inflammasome activation. These findings define the pathways that lead
      to rapid NLRP3 activation and identify IRAK1 as a critical mediator of a
      transcription-independent,inflammasome-dependent early warning response to
      pathogenic infection. 

PMID- 24043893
TI  - IL-21 enhances the activity of the TLR-MyD88-STAT3 pathway but not the classical
      TLR-MyD88-NF-kappaB pathway in human B cells to boost antibody production.
AB  - Both IL-21 and TLR agonists are important regulators of B cell responses, and the
      combination of IL-21 and TLR stimulation results in increased Ab production.
      However, it is not clear yet how IL-21 interacts with TLR signaling in B cells.
      In this study, we show that IL-21 enhances TLR-induced IgG production, whereas it
      has no effect on TLR-induced IL-6 production by human B cell cultures. These
      observations are explained by the finding that IL-21 augments TLR-induced IgG
      production via the TLR-MyD88-STAT3 pathway but not the classical TLR-MyD88-NF
      kappaB pathway. We further demonstrate that stimulation of human B cells with IL
      21 and TLR7/8 or TLR9 agonists increases the phosphorylation of STAT3, whereas
      the activation of NF-kappaB is not affected. Interestingly, like IL-21, IL-10 in
      combination with TLR signaling also enhances phosphorylation of STAT3, resulting
      in an increase of IgG production. Hence, IL-21 and IL-10 increase the activity of
      the TLR-MyD88-STAT3 pathway in human B cells via enhancing the phosphorylation of
      STAT3 for Ab production. 

PMID- 24043894
TI  - IL-33 markedly activates murine eosinophils by an NF-kappaB-dependent mechanism
      differentially dependent upon an IL-4-driven autoinflammatory loop.
AB  - Eosinophils are major effector cells in type 2 inflammatory responses and become
      activated in response to IL-4 and IL-33, yet the molecular mechanisms and
      cooperative interaction between these cytokines remain unclear. Our objective was
      to investigate the molecular mechanism and cooperation of IL-4 and IL-33 in
      eosinophil activation. Eosinophils derived from bone marrow or isolated from Il5
      transgenic mice were activated in the presence of IL-4 or IL-33 for 1 or 4 h, and
      the transcriptome was analyzed by RNA sequencing. The candidate genes were
      validated by quantitative PCR and ELISA. We demonstrated that murine-cultured
      eosinophils respond to IL-4 and IL-33 by phosphorylation of STAT-6 and NF-kappaB,
      respectively. RNA sequence analysis of murine-cultured eosinophils indicated that
      IL-33 induced 519 genes, whereas IL-4 induced only 28 genes, including 19 IL-33
      regulated genes. Interestingly, IL-33 induced eosinophil activation via two
      distinct mechanisms, IL-4 independent and IL-4 secretion/autostimulation
      dependent. Anti-IL-4 or anti-IL-4Ralpha Ab-treated cultured and mature
      eosinophils, as well as Il4- or Stat6-deficient cultured eosinophils, had
      attenuated protein secretion of a subset of IL-33-induced genes, including Retnla
      and Ccl17. Additionally, IL-33 induced the rapid release of preformed IL-4
      protein from eosinophils by a NF-kappaB-dependent mechanism. However, the
      induction of most IL-33-regulated transcripts (e.g., Il6 and Il13) was IL-4
      independent and blocked by NF-kappaB inhibition. In conclusion, we have
      identified a novel activation pathway in murine eosinophils that is induced by IL
      33 and differentially dependent upon an IL-4 auto-amplification loop. 

PMID- 24043895
TI  - Cutting edge: CD4 T cells reactive to an islet amyloid polypeptide peptide
      accumulate in the pancreas and contribute to disease pathogenesis in nonobese
      diabetic mice.
AB  - We previously reported a peptide KS20 from islet amyloid polypeptide (IAPP) to be
      the target Ag for a highly diabetogenic CD4 T cell clone BDC-5.2.9. To track IAPP
      reactive T cells in NOD mice and determine how they contribute to the
      pathogenesis of type 1 diabetes, we designed a new I-Ag7 tetramer with high
      affinity for BDC-5.2.9 that contains the peptide KS20. We found that significant
      numbers of KS20 tetramer(+) CD4 T cells can be detected in the pancreas of
      prediabetic and diabetic NOD mice. To verify pathogenicity of IAPP-reactive
      cells, we sorted KS20 tetramer(+) cells and cloned them from uncloned T cell
      lines isolated from spleen and lymph nodes of diabetic mice. We isolated a new
      KS20-reactive Th1 CD4 T cell clone that rapidly transfers diabetes. Our results
      suggest that IAPP triggers a broad autoimmune response by CD4 T cells in NOD
      mice. 

PMID- 24043896
TI  - Inhibition of breast cancer metastasis by resveratrol-mediated inactivation of
      tumor-evoked regulatory B cells.
AB  - We reported previously that tumor-evoked regulatory B cells (tBregs) play an
      essential role in breast cancer lung metastasis by inducing TGF-beta-dependent
      conversion of metastasis-promoting Foxp3(+) regulatory T cells (Tregs). In this
      article, we show that resveratrol (RSV), a plant-derived polyphenol, at low and
      noncytotoxic doses for immune cells, can efficiently inhibit lung metastasis in
      mice. The mechanism of this process is that RSV inactivates Stat3, preventing the
      generation and function of tBregs, including expression of TGF-beta. As a result,
      it frees antitumor effector immune responses by disabling tBreg-induced
      conversion of Foxp3(+) Tregs. We propose that low doses of RSV may also benefit
      humans by controlling cancer escape-promoting tBregs/Tregs without nonspecific
      inactivation of effector immune cells. 

PMID- 24043897
TI  - Cholera toxin directly enhances IL-17A production from human CD4+ T cells.
AB  - The significance of Th17 cells and IL-17A signaling in host defense and disease
      development has been demonstrated in various infection and autoimmune models.
      Additionally, the generation of Th17 cells is highly influenced by microbes.
      However, the specific bacterial components capable of shaping Th17 responses have
      not been well defined. The goals of this study were to understand how a bacterial
      toxin, cholera toxin (CT), modulates Th17-dominated response in isolated human
      CD4(+) T cells, and what are the mechanisms associated with this modulation.
      CD4(+) cells isolated from human peripheral blood were treated with CT. The
      levels of cytokine production and specific Th cell responses were determined by
      ELISA, Luminex assay, and flow cytometry. Along with the decreased production of
      other proinflammatory cytokines (IFN-gamma, TNF-alpha, and IL-2), we found that
      CT could directly enhance the IL-17A production through a cAMP-dependent pathway.
      This enhancement is specific for IL-17A but not for IL-17F, IL-22, and CCL20.
      Interestingly, CT could increase IL-17A production only from Th17-committed
      cells, such as CCR6(+)CD4(+) T cells and in vitro-differentiated Th17 cells.
      Furthermore, we also demonstrated that this direct effect occurs at a
      transcriptional level because CT stimulates the reporter activity in Jurkat and
      primary CD4(+) T cells transfected with the IL-17A promoter-reporter construct.
      This study shows that CT has the capacity to directly shape Th17 responses in the
      absence of APCs. Our findings highlight the potentials of bacterial toxins in the
      regulation of human Th17 responses. 

PMID- 24043898
TI  - Cutting edge: Mouse NAIP1 detects the type III secretion system needle protein.
AB  - The NAIP/NLRC4 inflammasomes activate caspase-1 in response to bacterial type III
      secretion systems (T3SSs). Inadvertent injection of the T3SS rod protein and
      flagellin into the cytosol is detected through murine NAIP2 and NAIP5/6,
      respectively. In this study, we identify the agonist for the orphan murine NAIP1
      receptor as the T3SS needle protein. NAIP1 is poorly expressed in resting mouse
      bone marrow-derived macrophages; however, priming with polyinosinic-polycytidylic
      acid induces it and confers needle protein sensitivity. Further, overexpression
      of NAIP1 in immortalized bone marrow-derived macrophages by retroviral
      transduction enabled needle detection. In contrast, peritoneal cavity macrophages
      basally express NAIP1 and respond to needle protein robustly, independent of
      priming. Human macrophages are known to express only one NAIP gene, which detects
      the needle protein, but not rod or flagellin. Thus, murine NAIP1 is functionally
      analogous to human NAIP. 

PMID- 24043899
TI  - RON receptor tyrosine kinase, a negative regulator of inflammation, is decreased
      during simian immunodeficiency virus-associated central nervous system disease.
AB  - Expressed on tissue-resident macrophages, the receptor tyrosine kinase, recepteur
      d'orgine nantais (RON), functions to maintain inflammation homeostasis by
      activating genes that promote wound repair and resolve inflammation while
      repressing genes that perpetuate tissue damage and cell death. Chronic HIV-1
      infection is associated with dysregulated inflammation, and we hypothesize that
      diminished RON expression contributes to the development of end organ diseases
      such as HIV-1-associated CNS disease. To explore RON function in vivo, we used
      CNS tissue from a well-characterized SIV macaque model and examined the temporal
      regulation of RON in the brain during the course of infection. Following
      prolonged SIV infection, RON expression was inversely correlated with the
      development of CNS disease; RON was maintained in animals that did not develop
      CNS lesions and was reduced in SIV-infected macaques that demonstrated moderate
      to severe inflammatory lesions. Arginase-1 expression was reduced in the brain
      during late infection, whereas expression of the inflammatory genes, IL-12p40 and
      TNF-alpha, was elevated. To validate a role for RON in regulating HIV-1 in
      primary cells, we used human tissue-resident macrophages isolated from tonsil as
      a tractable cell model. RON signaling in tissue-resident macrophages, both ligand
      dependent and independent, limited HIV-1 replication. Furthermore, prolonged HIV
      1 infection in vitro resulted in downregulation of RON. We propose a model in
      which, following chronic HIV-1 infection in the brain, RON expression is
      decreased, genes that quell inflammation are repressed, and inflammatory
      mediators are induced to promote tissue inflammation. 

PMID- 24043901
TI  - Role of complement activation in obliterative bronchiolitis post-lung
      transplantation.
AB  - Obliterative bronchiolitis (OB) post-lung transplantation involves IL-17
      regulated autoimmunity to type V collagen and alloimmunity, which could be
      enhanced by complement activation. However, the specific role of complement
      activation in lung allograft pathology, IL-17 production, and OB is unknown. The
      current study examines the role of complement activation in OB. Complement
      regulatory protein (CRP) (CD55, CD46, complement receptor 1-related protein
      y/CD46) expression was downregulated in human and murine OB; and C3a, a marker of
      complement activation, was upregulated locally. IL-17 differentially suppressed
      complement receptor 1-related protein y expression in airway epithelial cells in
      vitro. Neutralizing IL-17 recovered CRP expression in murine lung allografts and
      decreased local C3a production. Exogenous C3a enhanced IL-17 production from
      alloantigen- or autoantigen (type V collagen)-reactive lymphocytes. Systemically
      neutralizing C5 abrogated the development of OB, reduced acute rejection
      severity, lowered systemic and local levels of C3a and C5a, recovered CRP
      expression, and diminished systemic IL-17 and IL-6 levels. These data indicated
      that OB induction is in part complement dependent due to IL-17-mediated
      downregulation of CRPs on airway epithelium. C3a and IL-17 are part of a feed
      forward loop that may enhance CRP downregulation, suggesting that complement
      blockade could be a therapeutic strategy for OB. 

PMID- 24043902
TI  - Lithium attenuates IFN-beta production and antiviral response via inhibition of
      TANK-binding kinase 1 kinase activity.
AB  - Lithium salt is a widely used glycogen synthase kinase-3beta inhibitor and
      effective drug for the treatment of psychiatric diseases. However, the effects of
      lithium in innate immune responses, especially in cellular antiviral responses,
      are unknown. In this study, we show that lithium chloride attenuates LPS-,
      polyinosinic-polycytidylic acid-, and Sendai virus-induced IFN-beta production
      and IFN regulatory factor 3 activation in macrophages in a glycogen synthase
      kinase-3beta-independent manner. The ability of the lithium to inhibit IFN-beta
      production was confirmed in vivo, as mice treated with lithium chloride exhibited
      decreased levels of IFN-beta upon Sendai virus infection. In vitro kinase assay
      demonstrates that lithium suppresses TANK-binding kinase 1 kinase activity.
      Consistently, lithium significantly enhanced the replication of vesicular
      stomatitis virus in vitro and in vivo. Severe infiltration of monocytes and
      tissue damage were observed in the lungs of control mice, compared with lithium
      treated mice after virus infection. Our findings suggest lithium as an inhibitor
      of TANK-binding kinase 1 and potential target for the intervention of diseases
      with uncontrolled IFN-beta production. Furthermore, lithium attenuates host
      defense to virus infection and may cause severely adverse effects in clinical
      applications. 

PMID- 24043900
TI  - Heat shock transcription factor 1 is activated as a consequence of lymphocyte
      activation and regulates a major proteostasis network in T cells critical for
      cell division during stress.
AB  - Heat shock transcription factor 1 (HSF1) is a major transcriptional regulator of
      the heat shock response in eukaryotic cells. HSF1 is evoked in response to a
      variety of cellular stressors, including elevated temperatures, oxidative stress,
      and other proteotoxic stressors. Previously, we demonstrated that HSF1 is
      activated in naive T cells at fever range temperatures (39.5 degrees C) and is
      critical for in vitro T cell proliferation at fever temperatures. In this study,
      we demonstrated that murine HSF1 became activated to the DNA-binding form and
      transactivated a large number of genes in lymphoid cells strictly as a
      consequence of receptor activation in the absence of apparent cellular stress.
      Microarray analysis comparing HSF1(+/+) and HSF1(-/-) gene expression in T cells
      activated at 37 degrees C revealed a diverse set of 323 genes significantly
      regulated by HSF1 in nonstressed T cells. In vivo proliferation studies revealed
      a significant impairment of HSF1(-/-) T cell expansion under conditions mimicking
      a robust immune response (staphylococcal enterotoxin B-induced T cell
      activation). This proliferation defect due to loss of HSF1 is observed even under
      nonfebrile temperatures. HSF1(-/-) T cells activated at fever temperatures show a
      dramatic reduction in cyclin E and cyclin A proteins during the cell cycle,
      although the transcription of these genes was modestly affected. Finally, B cell
      and hematopoietic stem cell proliferation from HSF1(-/-) mice, but not HSF1(+/+)
      mice, were also attenuated under stressful conditions, indicating that HSF1 is
      critical for the cell cycle progression of lymphoid cells activated under
      stressful conditions. 

PMID- 24043904
TI  - Anti-human CD73 monoclonal antibody inhibits metastasis formation in human breast
      cancer by inducing clustering and internalization of CD73 expressed on the
      surface of cancer cells.
AB  - Recent studies have shown that Abs that target the cell-surface enzyme CD73 (ecto
      5'-nucleotidase) reduce growth of primary tumors and metastasis in syngenic mice
      by inhibiting the catalytic activity of CD73, and thus increasing the activity of
      cytotoxic T lymphocytes. In this article, we report another anticancer mechanism
      of anti-CD73 Abs and show that an anti-CD73 mAb (AD2) inhibits metastasis
      formation by a mechanism independent of CD73 catalytic activity and inhibition of
      primary tumor growth. This mechanism involves clustering and internalization of
      CD73, but does not require cross-linking of CD73, because both whole IgG anti
      CD73 AD2 mAb and Fab' fragments thereof exhibited this effect. Ex vivo treatment
      of different breast cancer cell lines with anti-CD73 AD2 mAb before i.v.
      injection into mice inhibited extravasation/colonization of circulating tumor
      cells and significantly reduced metastasis development. This effect was also
      observed when the cancer cell-surface expression of CD73 was significantly
      reduced by small interfering RNA knockdown. The antimetastatic activity is
      epitope specific, as another Ab that efficiently binds CD73-expressing live
      cancer cells did not lead to CD73 internalization and metastasis inhibition.
      Furthermore, anti-CD73 AD2 mAb inhibited development of metastasis in a
      spontaneous animal model of human metastatic breast cancer. Our study shows that
      some anti-CD73 mAbs cause cell-surface clustering of CD73 followed by
      internalization, thus inhibiting the ability of circulating tumor cells to
      extravasate and colonize, leading to inhibition of metastasis. Ab-based CD73
      cancer therapy should include a combination of Abs that target the catalytic
      activity of CD73, as well as those with the characteristics described in this
      article. 

PMID- 24043903
TI  - Both MC5r and A2Ar are required for protective regulatory immunity in the spleen
      of post-experimental autoimmune uveitis in mice.
AB  - The ocular microenvironment uses a poorly defined mela5 receptor (MC5r)-dependent
      pathway to recover immune tolerance following intraocular inflammation. This
      dependency is seen in experimental autoimmune uveoretinitis (EAU), a mouse model
      of endogenous human autoimmune uveitis, with the emergence of autoantigen
      specific regulatory immunity in the spleen that protects the mice from recurrence
      of EAU. In this study, we found that the MC5r-dependent regulatory immunity
      increased CD11b(+)F4/80(+)Ly-6C(low)Ly-6G(+)CD39(+)CD73(+) APCs in the spleen of
      post-EAU mice. These MC5r-dependent APCs require adenosine 2A receptor expression
      on T cells to activate EAU-suppressing CD25(+)CD4(+)Foxp3(+) regulatory T cells.
      Therefore, in the recovery from autoimmune disease, the ocular microenvironment
      induces tolerance through a melanocortin-mediated expansion of Ly-6G(+)
      regulatory APCs in the spleen that use the adenosinergic pathway to promote
      activation of autoantigen-specific regulatory T cells. 

PMID- 24043905
TI  - A Person-Centered Examination of Adolescent Religiosity Using Latent Class
      Analysis.
AB  - Empirical studies of religion's role in society, especially those focused on
      individuals and analyzing survey data, conceptualize and measure religiosity on a
      single measure or a summary index of multiple measures. Other concepts, such as
      "lived religion," "believing without belonging," or "fuzzy fidelity," emphasize
      what scholars have noted for decades: humans are rarely consistently low, medium,
      or high across dimensions of religiosity including institutional involvement,
      private practice, salience, or belief. A method with great promise for
      identifying population patterns in how individuals combine types and levels of
      belief, practice, and personal religious salience is latent class analysis. In
      this paper, we use data from the first wave of the National Study of Youth and
      Religion's telephone survey to discuss how to select indicators of religiosity in
      an informed manner, as well as the implications of the number and types of
      indicators used for model fit. We identify five latent classes of religiosity
      among adolescents in the United States and their socio-demographic correlates.
      Our findings highlight the value of a person-centered approach to understanding
      how religion is lived by American adolescents.

PMID- 24043906
TI  - WIC in Your Neighborhood: New Evidence on the Impacts of Geographic Access to
      Clinics.
AB  - A large body of evidence indicates that conditions in-utero and health at birth
      matter for individuals' long-run outcomes, suggesting potential value in programs
      aimed at pregnant women and young children. This paper uses a novel
      identification strategy and data from birth and administrative records over 2005
      2009 to provide causal estimates of the effects of geographic access to the
      Special Supplemental Nutrition Program for Women, Infants, and Children (WIC). My
      empirical approach uses within-ZIP-code variation in WIC clinic presence together
      with maternal fixed effects, and accounts for the potential endogeneity of
      mobility, gestational-age bias, and measurement error in gestation. I find that
      access to WIC increases food benefit take-up, pregnancy weight gain, birth
      weight, and the probability of breastfeeding initiation at the time of hospital
      discharge. The estimated effects are strongest for mothers with a high school
      education or less, who are most likely eligible for WIC services.

PMID- 24043907
TI  - In-vivo degradation of poly(carbonate-urethane) based spine implants.
AB  - Fourteen explanted Dynesys(r) spinal devices were analyzed for biostability and
      compared with a reference, never implanted, control. Both poly(carbonate
      urethane) (PCU) spacers and polyethylene-terephthalate (PET) cords were analyzed.
      The effect of implantation was evaluated through the observation of physical
      alterations of the device surfaces, evaluation of the chemical degradation and
      fluids absorption on the devices and examination of the morphological and
      mechanical features. PCU spacers exhibited a variety of surface damage
      mechanisms, the most significant being abrasion and localized, microscopic
      surface cracks. Evidence of oxidation and chain scission were detected on PCU
      spacers ATR-FTIR. ATR-FTIR, DSC and hardness measurements also showed a slight
      heterogeneity in the composition of PCU. The extraction carried out on the PCU
      spacers revealed the presence of extractable polycarbonate segments. One spacer
      and all PET cords visually exhibited the presence of adherent biological material
      (proteins), confirmed by the ATR-FTIR results. GC/MS analyses of the extracts
      from PET cords revealed the presence of biological fluids residues, mainly
      cholesterol derivatives and fatty acids, probably trapped into the fiber network.
      No further chemical alterations were observed on the PET cords. Although the
      observed physical and chemical damage can be considered superficial, greater
      attention must be paid to the chemical degradation mechanisms of PCU and to the
      effect of byproducts on the body.

PMID- 24043908
TI  - Zenker's diverticulum: exploring treatment options.
AB  - Zenker's diverticulum is an acquired sac-like outpouching of the mucosa and
      submucosa layers located dorsally at the pharyngoesophageal junction through
      Killian's dehiscence. It is the most common type of oesophageal diverticula with
      a reported prevalence ranging between 0.01 to 0.11% and typically occurs in
      middle-aged and elderly patients. Predominant symptoms are dysphagia and
      regurgitation. Treatment is recommended for symptomatic patients and considering
      the aetiopathogenesis of the disease demands myotomy of the cricopharyngeal
      muscle. Myotomy may be pursued through either open surgical or endoscopic
      techniques. Management of Zenker's diverticulum has dramatically progressed
      during past decades. Open surgery with cricopharyngeal myotomy has long been the
      conventional treatment with satisfactory results, but is associated with high
      complication rates. Since Zenker's diverticulum mainly affects frail elderly
      patients, less invasive treatments are indicated. In recent years, endoscopic
      repair of Zenker's diverticulum has been found to be a viable safe and effective
      alternative to surgery and gained widespread acceptance. Endoscopic stapled
      diverticulotomy is generally the preferred approach, but flexible endoscopy is a
      valuable option, particularly for high-risk patients. The literature is mainly
      based on retrospective case series or comparative case series, and the optimal
      treatment modality has not yet been established. The choice between the different
      approaches depends on local expertise and preferences. Based on retrospective
      literature results, appropriate technique selection dictated by the size of the
      diverticulum and the patient's conditions is however desirable. 

PMID- 24043909
TI  - Transoral robotic surgery (TORS) for tongue base tumours.
AB  - In recent years, transoral robotic surgery (TORS) has been used for the removal
      of pharyngeal and laryngeal cancers with the objective to improve functional and
      aesthetic outcomes without worsening the survival. This prospective single-centre
      cohort study described TORS in selected tumours of the tongue base in order to
      assess safety, efficacy and functional outcome of the procedure. From October
      2010 to February 2012, TORS was performed in 13 consecutive patients affected by
      T1-T2 tumours of the base of the tongue. This procedure was applicable in all
      cases. The clinical stage demonstrated 8 T1 tumours and 5 T2 tumours. Neck node
      metastases were clinically evident in 6 cases (7 N0, 1 N1, 4 N2b and 1 N2c). The
      final pathology report confirmed malignancy in all cases (11 squamous cell
      carcinoma and 2 mucoepidermoid carcinoma). Negative-margin resections were
      obtained in all cases but one with close margins. Synchronous lymph node neck
      dissections were performed in 7 cases (6 monolateral, 1 bilateral). Patients
      underwent temporary tracheostomies for a mean time of 6 days. A naso-gastric
      feeding tube was positioned in 10/13 (76.9%) patients for a mean time of 7.5
      days. The average time to carry out the TORS procedure was 95 min (set-up time 25
      min; TORS 70 min). No deaths occurred. Surgical complications were observed in 4
      cases (postoperative bleedings in 3 cases and intraoperative anaphylactic shock
      in 1 case). Median hospital stay was 9 days. All patients had good functional
      outcomes. Adjuvant treatment was indicated in 5/13 cases (35.4%). TORS represents
      a good tool for staging and treating neoplasm of the base of the tongue. The
      transoral removal is safe and can radically remove limited oropharyngeal tumours
      of the tongue base with good functional outcomes. The operating costs can be
      relatively high but they are related to the number of procedures per year,
      although the advantages to patients seem to justify the procedure. TORS can
      represent the definitive treatment in selected T1-T2 cases of base of the tongue
      tumours without adverse features and allow the possibility for the
      deintensification of adjuvant treatments. 

PMID- 24043910
TI  - The effect of substitution therapy on symptoms in patients with hypothyroidism
      following treatment for laryngeal and hypopharyngeal carcinomas.
AB  - Hypothyroidism is a well-known complication following treatment of laryngeal or
      hypopharyngeal carcinomas, and may cause various psychological and physical
      problems that negatively affect quality of life. The aim of this study was to
      evaluate the effect of substitution therapy on symptoms in patients with
      hypothyroidism. A study-specific questionnaire on physical and psychological
      problems (before and after substitution therapy) was sent to 70 patients who had
      been treated between 1977 and 2008 with clinical or subclinical hypothyroidism.
      Ninety-four percent returned the questionnaire. Symptoms on energy levels were
      reported most often (67% always tired and 70% lack of energy). Moodiness and
      emotional and physical symptoms were reported more often in substituted
      (sub)clinical hypothyroidism. Substitution therapy resulted in an improvement of
      energy (P = 0.013), sense of general interest and enjoyment (P = 0.022) and a
      reduction of puffy face (P = 0.041). Most symptoms in patients with thyroid
      dysfunction do not improve after substitution therapy. Nevertheless, due to its
      impact on health-related quality of life and the low burden of substitution
      therapy, screening for hypothyroidism and subsequent substitution therapy remains
      important. 

PMID- 24043911
TI  - Effect of vitamin B12 deficiency on otoacoustic emissions.
AB  - The aim of this study was to investigate the possible association between
      otoacoustic emission (OAE) values and cochlear function in patients with vitamin
      B12 deficiency and no evidence of symptomatic hearing loss. Two groups were
      studied: Group 1: patients with vitamin B12 deficiency; Group 2: a matched
      control group of patients with normal vitamin B12 levels. There was no evidence
      of symptomatic hearing loss in either group. Transiently evoked OAEs (TEOAEs) and
      spontaneous OAEs (SOAEs) were recorded. A comparative analysis of the studied
      parameters revealed that results at TEOAE 1000, SOAEs 1500 and SOAEs 4000 Hz were
      somewhat lower in the vitamin B12 deficient group compared with the control
      group. According to our findings, there was a significant association between
      vitamin B12 deficiency and cochlear dysfunction. We recommend that routine
      vitamin B12 serum levels be determined when evaluating patients for symptomatic
      hearing loss. 

PMID- 24043912
TI  - Evaluation of total oxidative stress parameters in patients with nasal polyps.
AB  - Oxidative stress, an imbalance between reactive oxygen species production and
      antioxidative defense activity, is believed to have a role in the development and
      pathogenesis of nasal polyps (NPs). Based on this assumption, several known
      oxidants and antioxidants have been studied in patients with NPs. The purpose of
      this study was to evaluate the association between oxidative stress parameters
      with a more valid and reliable method in patients with NPs. Seventy-three
      patients with NPs, septal deviations and middle concha hypertrophies were
      recruited. Patients were divided into two groups; group 1 (n = 38) consisted of
      patients with NPs, and group 2 (n = 35) included patients with septal deviations
      and middle concha hypertrophies. Polyp specimens were taken from all patients who
      underwent endoscopic surgery for NPs. Control specimens were obtained from
      patients who underwent an operation for septoplasty or middle concha hypertrophy.
      Blood and tissue samples were obtained to assess total oxidant status (TOS),
      total antioxidant status (TAS) and oxidative stress index (OSI). Compared to
      group 2, group 1 had significantly higher TOS and OSI and lower TAS levels both
      in serum and tissue samples (p < 0.001 for all). In group 1, tissue TOS and OSI
      levels were significantly higher, and TAS levels were significantly lower than in
      serum (p < 0.001 for all), whereas no significant difference was found in TOS,
      OSI and TAS levels either in serum or tissue samples in group 2 (p = 1.0; p = 1;
      p = 0.208, respectively). In group 1, serum OSI levels were significantly
      correlated with age (r = 0.442, p = 0.005). Our study demonstrated that oxidative
      stress, both in serum and tissues in patients with NPs, was higher than in
      patients without NPs. Our study differs from previous studies in that we used a
      more reliable method that measures both TOS and TAS. 

PMID- 24043913
TI  - Direction-fixed paroxysmal nystagmus lateral canal benign paroxysmal positioning
      vertigo (BPPV): another form of lateral canalolithiasis.
AB  - Benign paroxysmal positioning vertigo (BPPV) is the most frequent vertiginous
      syndrome. It is caused either by free-floating otoliths in the semicircular
      canals (canalolithiasis) or by otoconial debris adhering to a canal cupula
      (cupulolithiasis). The posterior canal is the most frequently involved (80%),
      while the lateral canal is involved less frequently (15%), and the rarest
      conditions are anterior canalolithiasis and apogeotropic posterior
      canalolithiasis (5%). The main diagnostic sign of lateral canal BPPV is
      paroxysmal horizontal bidirectional positioning nystagmus evoked through Pagnini
      McClure's test (head roll in the yaw plane in supine position). In the geotropic
      variant, which is more frequent, the fast phase of the nystagmus is directed
      towards the lowermost ear, when the patient lies on the affected side or on the
      healthy side; in the apogeotropic variant, which is less frequent, the fast phase
      is directed always toward the uppermost ear, regardless of which side the patient
      lies on. Paroxysmal nystagmus is more intense on the affected side in the
      geotropic form, and more intense on the healthy side in the apogeotropic form.
      The authors describe five cases of another primitive and rare form of lateral
      BPPV, defined as "direction-fixed paroxysmal nystagmus lateral canal BPPV", which
      has previously been described by other authors as a transitory step observed
      during the transformation from an apogeotropic into a geotropic form. It is
      characterized by typical BPPV symptoms and diagnosed by the presence of a
      paroxysmal horizontal unidirectional positioning nystagmus, evoked through
      Pagnini-McClure's test, which is apogeotropic on the affected side and geotropic
      on the healthy side. In the reported cases, direction-fixed horizontal paroxysmal
      nystagmus was always transformed into a typical geotropic form. The clinical
      features and pathophysiology of direction-fixed nystagmus lateral canal BPPV are
      discussed. 

PMID- 24043914
TI  - Identification of obstructive sites and patterns in obstructive sleep apnoea
      syndrome by sleep endoscopy in 614 patients.
AB  - The aim of this study was to analyze and report sites and patterns of obstruction
      observed during sleep endoscopy in a large group of patients and suggest
      consequent therapeutic prescriptions. 614 consecutive patients who approached the
      Centre for Diagnosis and Treatment of Respiratory Sleep Disorders underwent sleep
      endoscopy. We used propofol to induce sleep, monitoring the value of bispectral
      index to evaluate the depth of sedation. For each patient, we recorded
      obstruction sites,obstruction patterns and the effects of the mandibular pull-up
      manoeuvre on both obstruction and snoring. We ascertained that, in almost all
      patients, the noise of snoring was generated at the oropharyngeal level. The
      obstruction at the oropharyngeal level, either in isolation or in combination
      with other structures, is far more common. The mandibular pull-up manoeuvre was
      effective in reducing or resolving the obstruction in a large number of patients,
      even though their AHI values were high. For those patients having an AHI over 15,
      we point out the various therapeutic indications gained from the sleep endoscopy
      examinations. Drug-induced (propofol) sleep endoscopy can be considered be a safe
      procedure, easily practicable, valid and reliable; we therefore consider it a
      fundamental clinical investigation that can be essential when choosing treatment.

PMID- 24043915
TI  - Management of otolaryngological manifestations in mucopolysaccharidoses: our
      experience.
AB  - Mucopolysaccharidoses (MPSs) are lysosomal storage disorders caused by deficiency
      of enzymes involved in the degradation of glycosaminoglycans (GAGs). These
      disorders are associated with the accumulation of GAGs in tissues with
      organomegaly, mental retardation and short stature. Otologic and upper
      respiratory tract pathologies are among the earliest clinical manifestations. We
      analyzed 20 patients (13 male and 7 female, median age at the beginning of the
      observation 6 years) with MPS (35% type I, 30% type II, 20% type III, 5% type IV,
      10% type VI), focusing on their otorhinolaryngologic problems and the impact of
      surgery on quality of life. We found ear, nose and throat manifestations in all
      types of MPS; in particular, recurrent otitis media was present in 30% of cases,
      hearing loss in 75% (mixed in 43.33%, conductive in 43.33%, sensorineural in
      13.33%), adenotonsillar hypertrophy in 75%, frequent infections of the upper
      airway in 75% and obstructive sleep apnoea syndrome in 45% of cases. Fifty
      percent of patients required surgical therapy (adenotonsillectomy, adenoidectomy
      with insertion of middle ear ventilation tubes, tonsillectomy, tracheotomy and
      exeresis of vocal cord polyps). In our experience the ENT surgery reduced the
      frequency and severity of ear infections and relieved symptoms related to upper
      airway obstruction, thereby improving the quality of life in affected patients. 

PMID- 24043916
TI  - Assessment of skills using a virtual reality temporal bone surgery simulator.
AB  - Surgery on the temporal bone is technically challenging due to its complex
      anatomy. Precise anatomical dissection of the human temporal bone is essential
      and is fundamental for middle ear surgery. We assessed the possible application
      of a virtual reality temporal bone surgery simulator to the education of ear
      surgeons. Seventeen ENT physicians with different levels of surgical training and
      20 medical students performed an antrotomy with a computer-based virtual temporal
      bone surgery simulator. The ease, accuracy and timing of the simulated temporal
      bone surgery were assessed using the automatic assessment software provided by
      the simulator device and additionally with a modified Final Product Analysis
      Scale. Trained ENT surgeons, physicians without temporal bone surgical training
      and medical students were all able to perform the antrotomy. However, the highly
      trained ENT surgeons were able to complete the surgery in approximately half the
      time, with better handling and accuracy as assessed by the significant reduction
      in injury to important middle ear structures. Trained ENT surgeons achieved
      significantly higher scores using both dissection analysis methods. Surprisingly,
      there were no significant differences in the results between medical students and
      physicians without experience in ear surgery. The virtual temporal bone training
      system can stratify users of known levels of experience. This system can be used
      not only to improve the surgical skills of trained ENT surgeons for more
      successful and injury-free surgeries, but also to train inexperienced
      physicians/medical students in developing their surgical skills for the ear. 

PMID- 24043917
TI  - Extended-pedicle peroneal artery perforator flap in intraoral reconstruction.
AB  - The peroneal artery perforator (PNAP) flap is a good choice for reconstruction in
      intraoral soft-tissue rehabilitation. In this article, the authors propose the
      use of a modified PNAP flap with pedicle extension. 

PMID- 24043918
TI  - Mucoepidermoid carcinoma of the tonsil: a very rare presentation.
AB  - Mucoepidermoid carcinoma is the most common malignant salivary gland tumour.
      However, short series or individual case reports have identified this tumour in
      the maxilla, mandible, breast tissue and thymus. Mucoepidermoid carcinoma
      originates from minor salivary glands, and it is therefore surprising that it is
      not more commonly seen in the tonsil. To date, we believe there has been only one
      previously reported case in the world literature of mucoepidermoid carcinoma
      occurring in the tonsil 1. We present a very rare case of mucoepidermoid
      carcinoma arising from within the structure of the palatine tonsil, rather from
      the adjacent pharyngeal wall, together with a short review of the literature. 

PMID- 24043919
TI  - Rural livelihood change? Household capital, community resources and livelihood
      transition.

PMID- 24043920
TI  - Socioeconomic Factors in Relation to Discrepancy in Parent versus Teacher Ratings
      of Child Behavior.
AB  - Discrepancies between observers are common in studies of child behavior problems
      that rely on behavior ratings. Although modest concordance between informants is
      well-documented, little is known about characteristics that predict
      discrepancies. In 477 children aged 5 to 12 years, maternal age and indicators of
      socioeconomic status (SES; maternal education, family income) were evaluated in
      relation to score discrepancies between the Child Behavior Checklist and Teacher
      Report Form for Total, Externalizing and Internalizing Problems. Family income
      <$35,000 was independently associated with discrepancies in which mothers rated
      more clinically significant child behavior problems than teachers for Total,
      Externalizing and Internalizing Problems [odds ratio (OR) = 3.26, 95% confidence
      interval (CI ), 1.19-8.96, OR = 2.76, 95% CI 1.03-7.34 and OR = 3.07, 95% CI 1.30
      7.26, respectively]. Maternal education was not associated with discrepancies,
      but younger mothers were less likely to rate child's behavior in the clinical
      range for Externalizing Problems than teachers (OR per year of age = 0.88, 95% CI
      0.81-0.96). These results suggest that studies that utilize only maternal or
      teacher report of child behavior may have misclassification of outcomes that is
      dependent on SES and could produce biased results.

PMID- 24043921
TI  - Intervention Effects on Health-Risking Sexual Behavior Among Girls in Foster
      Care: The Role of Placement Disruption and Tobacco and Marijuana Use.
AB  - The present study examined the effects of the Middle School Success intervention
      (MSS), a program to promote healthy adjustment in foster girls, on their health
      risking sexual behavior, using a randomized controlled trial (RCT) design. As
      hypothesized, girls in the intervention condition (n = 48) showed significantly
      lower levels of health-risking sexual behavior than did girls in the control
      condition (n = 52) at 36 months postbaseline. Further path analysis indicated
      that this intervention effect was fully mediated through its effects on girls'
      tobacco and marijuana use. Findings highlight the importance of providing
      preventive intervention services to foster girls during early adolescence.

PMID- 24043922
TI  - Mindfulness-Based Stress Reduction for Low-Income, Predominantly African American
      Women With PTSD and a History of Intimate Partner Violence.
AB  - In this article, we consider the use of Mindfulness-Based Stress Reduction (MBSR)
      (Kabat-Zinn, 1991) as a community-based intervention to reduce health disparities
      for low-income, predominantly African American women with a history of intimate
      partner violence (IPV) and posttraumatic stress disorder (PTSD). This article
      presents our rationale for using MBSR as an intervention with this population,
      the details of its implementation, and a discussion of the feasibility and
      acceptability of the intervention based on participants' feedback and our
      observations. We conclude that the use of MBSR programs for low-income,
      predominantly African American women with PTSD and a history of IPV is both
      feasible (of initial interest to and completed by most participants) and
      acceptable (congruent with and relevant to their needs). Replication with larger
      samples and examination of mechanisms is warranted by these findings.

PMID- 24043923
TI  - Excavating Culture: Disentangling Ethnic Differences from Contextual Influences
      in Parenting.
AB  - Historically, much of the research on parenting has not disentangled the
      influences of race/ethnicity, SES, and culture on family functioning and the
      development of children and adolescents. This special issue addresses this gap by
      disentangling ethnic differences in parenting behaviors from their contextual
      influences, thereby deepening understanding of parenting processes in diverse
      families. Six members of the Parenting section of the Study Group on Race,
      Culture and Ethnicity (SGRCE) introduce and implement a novel approach toward
      understanding this question. The goal of this project is to study culturally
      related processes and the degree to which they predict parenting. An iterative
      process was employed to delineate the main parenting constructs (warmth,
      psychological and behavioral control, monitoring, communication, and self
      efficacy), cultural processes, and contextual influences, and to coordinate a
      data analytic plan utilizing individual datasets with diverse samples to answer
      the research questions.

PMID- 24043924
TI  - Evaluation of community eye outreach programs for early glaucoma detection in
      Nigeria.
AB  - PURPOSE: To evaluate the relevance of community eye outreach programs in the
      early detection of glaucoma patients in southwest Nigeria. METHODS: This was a
      retrospective, cross-sectional study that was conducted among glaucoma patients
      referred to the eye clinic of the University College Hospital (UCH), Ibadan,
      Nigeria, between January 2009 and December 2010 from different sources, including
      community eye outreach programs. The source of referral, stage of glaucoma, and
      visual field were recorded. RESULTS: Six hundred and fifty-three patients were
      studied during this period. The mean age was 56.3 years +/- 16.6 years, with a
      median age of 60 years. Patients referred from eye outreach programs were more
      likely to have mild to moderate disease than patients referred from other
      sources, who were more likely to have severe disease according to both the optic
      nerve head assessment (P < 0.01, Pearson's Chi-square = 10.67, odds ratio = 1.7
      [confidence interval = 1.23-2.31]) and visual field assessment (24-2) (P < 0.01,
      Pearson's Chi-square = 6.07, odds ratio = 1.5 [confidence interval = 1.08-2.03]).
      CONCLUSION: Community eye outreach programs appear highly useful in the earlier
      detection of glaucoma in sub-Saharan Africa.

PMID- 24043925
TI  - Evaluation of corneal changes after myopic LASIK using the Pentacam(r).
AB  - BACKGROUND: In this study, we used a Pentacam(r) device to evaluate the corneal
      changes that occur after laser-assisted in situ keratomileusis (LASIK). METHODS:
      Our study included 60 eyes of 32 patients. All patients were treated for myopia
      and myopic astigmatism using LASIK. The eyes were examined preoperatively and 3
      months postoperatively using a Pentacam to assess corneal changes with regard to
      curvature, elevation, and asphericity of the cornea. RESULTS: A statistically
      significant decrease in mean keratometric power of the anterior corneal surface
      (P = 0.001) compared with its pre-LASIK value was detected after 3 months, but
      there was no significant change in keratometric power of the posterior surface (P
      = 0.836). Asphericity (Q-value) of the anterior and posterior surfaces increased
      significantly after LASIK (P = 0.001). A significant forward bulge of the
      anterior corneal surface 4 mm and 7 mm from the central zone was detected 3
      months post-LASIK (P = 0.001 for both), but there was no significant increase in
      posterior elevation at 4 mm and 7 mm from the center (P = 0.637 and P = 0.26,
      respectively). No cases of post-LASIK ectasia were detected. Correlation between
      different parameters of the corneal surface revealed an indirect relation between
      changes in pachymetry and anterior corneal elevation at 4 mm and 7 mm from the
      central zone (r = -0.27, P = 0.13, and r = -0.37, P = 0.04, respectively), and a
      direct proportion between changes in pachymetry and mean keratometric power of
      the anterior and posterior corneal surfaces (r = 0.7, P = 0.001 and r = 0.4, P =
      0.028, respectively). CONCLUSION: LASIK causes significant changes at the
      anterior corneal surface but the effect is subtle and insignificant at the
      posterior surface.

PMID- 24043926
TI  - Effects of intravitreal bevacizumab on reduced visual acuity and macular
      thickness secondary to branch retinal vein occlusion.
AB  - BACKGROUND: The purpose of this study was to evaluate the effects of intravitreal
      bevacizumab injection in the treatment of macular thickness and reduced visual
      acuity in patients with branch retinal vein occlusion. METHODS: In this
      retrospective study, we evaluated 15 eyes of 15 consecutive patients diagnosed
      with branch retinal vein occlusion between May 2008 and June 2011 at our
      institution. Detailed ophthalmologic examination, optical coherence tomography,
      and/or fundus fluorescein angiography was performed at diagnosis and during
      follow-up. A 1.25 mg intravitreal bevacizumab injection was administered to all
      patients on average 2.73 (1-7) times. Visual acuity and macular thickness were
      evaluated before and after treatment. RESULTS: Eleven patients were female
      (73.3%) and four were male (26.6%). The mean patient age was 62.6 years. The
      patients were followed for a mean of 11.4 (range 4-24) months. Mean best
      corrected visual acuity was 0.92 +/- 0.52 logMAR (logarithm of the minimum angle
      of resolution) before treatment and 0.66 +/- 0.42 logMAR at the last examination.
      The increase in visual acuity was found to be statistically significant (P =
      0.031). Mean macular thickness was 395.46 +/- 106.55 MUm before treatment and
      302.26 +/- 84.6 MUm after the final treatment. The decrease in macular thickness
      was statistically significant (P < 0.001). CONCLUSION: Intravitreal bevacizumab
      injection was effective for treatment of retinal vein branch occlusion.

PMID- 24043927
TI  - Ophthalmic viscoelastic device injection for the treatment of flat anterior
      chamber after trabeculectomy: a case series study.
AB  - PURPOSE: Flat anterior chamber (FAC) in association with overfiltration is a
      complication after trabeculectomy. The aim of the current study was to
      investigate the efficacy of injection of an ophthalmic viscoelastic device (OVD)
      to treat FAC after trabeculectomy in a retrospective consecutive case series
      study. MATERIALS AND METHODS: Twenty-five consecutive patients who underwent
      injection of OVD for the treatment of FAC after trabeculectomy were analyzed. The
      primary outcome variable was the qualified success of trabeculectomy, which was
      defined at three different levels by the achievement of one of three IOP-related
      criteria with or without glaucoma medication. Kaplan-Meier plots were generated
      to estimate survival functions for trabeculectomy with OVD injection. RESULTS:
      Twenty-one patients (21/25 = 84.0%) recovered from FAC by one OVD injection. The
      postoperative intraocular pressure (IOP) measured at 12 months, 24 months, 36
      months, 48 months, and 60 months was 14.7 +/- 3.6 mmHg, 15.6 +/- 7.0 mmHg, 14.2
      +/- 2.8 mmHg, 14.2 +/- 3.8 mmHg, and 14.6 +/- 2.7 mmHg, respectively. All
      postoperative IOP measurements were significantly lower than the preoperative IOP
      (P < 0.001). The probabilities of qualified success for 5 years after
      trabeculectomy with OVD injection were as follows: 24.4% (IOP ? 21 mmHg and ?20%
      reduction of preoperative IOP), 16.5% (IOP ? 16 mmHg and ?20% reduction) and 6.3%
      (IOP ? 12 mmHg and ?30% reduction). One patient, who had undergone deep lamellar
      keratoplasty, experienced a complication associated with the injection of the
      viscoelastic material, Descemet's membrane detachment. CONCLUSION: Injection of
      OVD may be effective for the treatment of FAC; however, the long-term success
      rate was relatively low.

PMID- 24043928
TI  - Late vitreomacular traction in toxoplasma retinochoroiditis resolved by
      vitrectomy.
AB  - This paper reports a case of late vitreomacular traction in a young patient
      secondary to toxoplasma retinochoroiditis resolved by vitrectomy. A 17-year-old
      female with chronic inflammatory bowel disease developed severe vitreomacular
      traction 8 months after resolution of ocular toxoplasmosis with medical therapy.
      Best-corrected visual acuity, full ophthalmic slit-lamp examination, colour
      fundus photography, spectral domain optical coherence tomography, and fluorescein
      angiography were performed. The patient underwent vitrectomy with removal of the
      clinically evident posterior hyaloid. Vitrectomy was rapidly successful in
      resolving the vitreomacular traction, with full recovery in best-corrected visual
      acuity of 20/20. Vitreoretinal traction in patients with previous toxoplasma
      retinochoroiditis may appear several months after resolution of the inflammatory
      condition. We suggest observing carefully for possible development of late
      vitreoretinal traction during follow-up of such patients. 

PMID- 24043929
TI  - Emerging treatment options for meibomian gland dysfunction.
AB  - Meibomian gland dysfunction (MGD) is one of the most common diseases observed in
      clinics; it influences a great number of people, and is the leading cause of
      evaporative dry eye. Given the increased recognition of the importance of MGD, a
      great amount of attention has been paid to therapies targeting this condition.
      The traditional treatments of MGD consist of warm compresses and lid hygiene for
      removing an obstructed meibum, as well as antibiotics and anti-inflammatory
      agents to improve the quality of the meibum. However, each of these treatments
      has a different shortcoming and the treatment of MGD remains challenging. Despite
      the numerous possible treatment options for MGD, it is still difficult to obtain
      complete relief of signs and symptoms. This review focuses on current emerging
      treatment options for MGD including intraductal meibomian gland probing, emulsion
      eye drops containing lipids, the LipiFlow(r) thermal pulsation system, N-acetyl
      cysteine, azithromycin, oral supplementation with omega-3 essential fatty acids,
      and cyclosporine A. 

PMID- 24043930
TI  - Adherence in adults with type 1 diabetes mellitus correlates with treatment
      satisfaction but not with adverse events.
AB  - PURPOSE: Diabetes self-care and self-monitoring adherence has a positive effect
      on the metabolic control of the disease. The aim of this study was to analyze the
      adherence to self-care recommendations and to identify its correlates in adults
      with type 1 diabetes mellitus. PATIENTS AND METHODS: One hundred and eleven
      patients with type 1 diabetes were enrolled in an observational cross-sectional
      study conducted at the Diabetes Center of the University Hospital in Hradec
      Kralove, Czech Republic. Diabetes self-care adherence was measured by the Self
      Care Inventory-Revised, and treatment satisfaction by the Diabetes Treatment
      Satisfaction Questionnaire-status version. Additional data were collected from
      self-administered questionnaires and medical records. The Mann-Whitney test,
      Spearman correlations, and multiple linear regressions were used in the
      statistical analysis. RESULTS: The mean age of patients was 42.4 years; 59.5% of
      them were females and 53.2% of all patients used an insulin pump. The mean
      glycosylated hemoglobin (HbA1c) was 66.2 +/- 15.3 mmol/mol and the mean insulin
      dosage was 0.6 +/- 0.3 IU insulin/kg/day. The number of hypoglycemic episodes
      (including severe) that patients had in the last month before taking the survey
      was 3.6 +/- 3.2. Self-care adherence was associated with treatment satisfaction
      (0.495; P = 0.004) along with frequency of self-monitoring of before meal blood
      glucose (0.267; P = 0.003). It was not associated with the incidence of
      hypoglycemic events or any other insulin therapy-related problems or with socio
      demographic or clinical characteristics. CONCLUSION: Treatment satisfaction is
      one of the key factors that need to be targeted to maximize benefits to patients.
      Self-care adherence in adults with type 1 diabetes did not correlate with socio
      demographic and clinical characteristics, nor with adverse events.

PMID- 24043931
TI  - An analysis of fat-related and fiber-related behavior in men and women with type
      2 diabetes mellitus: key findings for clinical practice.
AB  - BACKGROUND: Despite the efforts of health care providers, adherence of patients
      with type 2 diabetes to the recommended diet is poor. The aim of this study was
      to describe the eating habits with emphasis on fat and fiber-related behavior
      (FFB) as well as the relationship between FFB behavior and parameters of diabetes
      control in men and women with type 2 diabetes mellitus. METHODS: The subjects in
      this observational cross-sectional study were 200 patients (54.5% male, mean age
      66.2 +/- 10.1 years, mean Diabetes Control and Complications Trial [DDCT]
      glycosylated hemoglobin [HbA1c] 7.6% +/- 1.7%) recruited from diabetes outpatient
      clinics in the Czech Republic. The subjects filled out the Fat- and Fiber-related
      Diet Behavior Questionnaire. The most recent patient data on diabetes control and
      drug therapy were derived from patient medical records. RESULTS: Patients tend to
      modify the dishes they are used to, rather than remove them completely from their
      diet and replace them by other types of foods. It is easier to perform healthier
      fat-related behaviors than fiber-related ones. Women scored significantly better
      than men on the fat-related diet habits summary scale (P = 0.002), as well as on
      "modify meat" (P = 0.001) and "substitute specially manufactured low-fat foods"
      (P = 0.045) subscales. A better score on the fat-related diet habits summary
      scale was significantly associated with higher HbA1c (rho = -0.248; P = 0.027)
      and higher waist circumference (rho = -0.254; P = 0.024) in women. CONCLUSION:
      Type 2 diabetes patients are likely to vary in their FFB behavior, and their
      dietary habits depend on gender. Health care professionals should pay attention
      to these facts when providing specific education. Emphasis should be placed on
      how to increase the fiber intake in diabetic patients.

PMID- 24043932
TI  - Liposomal extended-release bupivacaine for postsurgical analgesia.
AB  - When physicians consider which analgesia to use postsurgery, the primary goal is
      to relieve pain with minimal adverse side effects. Bupivacaine, a commonly used
      analgesic, has been formulated into an aqueous suspension of multivesicular
      liposomes that provide long-lasting analgesia for up to 72 hours, while avoiding
      the adverse side effects of opioids. The increased efficacy of liposomal extended
      release bupivacaine, compared to bupivacaine hydrochloride, has promoted its
      usage in a variety of surgeries including hemorrhoidectomy, bunionectomy,
      inguinal hernia repair, total knee arthroplasty, and augmentation mammoplasty.
      However, like other bupivacaine formulations, the liposomal extended-release
      bupivacaine does have some side effects. In this brief review, we provide an
      update of the current knowledge in the use of bupivacaine for postsurgical
      analgesia. 

PMID- 24043933
TI  - The preference for an endoscopist specific sex: a link between ethnic origin,
      religious belief, socioeconomic status, and procedure type.
AB  - BACKGROUND AND AIM: The sex of the physician performing the endoscopic procedure
      is one of the parameters influencing patient satisfaction. Our aim was to
      characterize patients' preferences according to their sex, socioeconomic status,
      and religious beliefs and according to procedure-related variables. METHODS: All
      patients undergoing an endoscopic procedure at Sheba Hospital between April 2012
      and September 2012 were asked to complete a questionnaire regarding their sex,
      ethnic background, socioeconomic status, religious practice, and preference for
      an endoscopist of a specific sex. Questionnaires were included for analysis only
      when more than 95% of the items were addressed. RESULTS: A total of 1,009
      patients agreed to complete the questionnaires; of these 946 (94% [59% male])
      were eligible for inclusion. Most patients (675 [70%]) expressed no preference
      for sex of the endoscopist, while 234 patients (25%) preferred a same-sex
      endoscopist, and only 55 (6%) preferred an other-sex endoscopist. Stepwise
      logistic regression analysis showed that in female patients, lower education
      (odds ratio [OR] = 1.28), non-Jewish religion (OR = 4.86), orthodox religious
      practice (OR = 2.28), African or Asian ethnic origin (OR = 2.44), scheduled for
      colonoscopy (OR = 1.90), and no previous endoscopy experience (OR = 1.88) were
      all associated with a preference for a same-sex endoscopist. CONCLUSION: One
      quarter of patients preferred the physician performing their examination to be of
      particular sex. Most of these patients preferred a same-sex endoscopist.
      Education level, intensity of religious practice, ethnic origin, and type of
      endoscopic examination were associated with a preference for a same-sex
      endoscopist. Addressing patients' preferences may improve the atmosphere in the
      clinical environment, reduce stress, and facilitate better treatment and
      adherence to endoscopic surveillance programs.

PMID- 24043934
TI  - Exploring the information needs of patients with unexplained chest pain.
AB  - BACKGROUND: Unexplained chest pain is a common condition. Despite negative
      findings, a large number of these patients will continue to suffer from chest
      pain after being investigated at cardiac outpatient clinics. Unexplained chest
      pain covers many possible complaints, and diagnosing a single cause for a
      patient's pain is often described as difficult, as there are a number of possible
      factors that can contribute to the condition. For health professionals to meet
      patients' expectations, they must know more about the information needs of
      patients with unexplained chest pain. The aim of this study was to describe
      information needs among patients with unexplained chest pain and how those needs
      were met by health professionals during medical consultations. METHODS: A
      qualitative design was used. Data were collected by means of seven individual
      interviews with four women and three men, aged 21-62 years. The interviews were
      analyzed by qualitative content analysis. RESULTS: The results are described in
      two subthemes, ie, "experiencing lack of focus on individual problems" and
      "experiencing unanswered questions". These were further abstracted under the main
      theme "experiencing unmet information needs". CONCLUSION: Existing models of
      consultations should be complemented to include a person-centered approach to
      meeting patients' beliefs, perceptions, and expressions of feelings related to
      experiencing unexplained chest pain. This is in line with a biopsychosocial model
      with active patient participation, shared decision-making, and a
      multidisciplinary approach. Such an approach is directly within the domain of
      nursing, and aims to take into account patient experience.

PMID- 24043935
TI  - Treatment of invasive candidiasis in the elderly: a review.
AB  - Fungi are major causes of infections among immunocompromised or hospitalized
      patients with serious underlying diseases and comorbidities. Candida species
      remain the most important cause of opportunistic infections worldwide, affecting
      predominantly patients over 65 years old, while they are considered to be the
      fourth most common cause of nosocomial bloodstream infections. The rapidly
      growing elderly population has specific physiological characteristics, which
      makes it susceptible to colonization and subsequent infection due to Candida
      species. Comorbidities and multidrug use should be taken into account any time
      the therapeutic regimen is under consideration. Different classes of antifungal
      drugs are available for the treatment of invasive fungal infections but
      echinocandins, apart from their activity against resistant strains (Candida
      glabrata and Candida krusei), seem to be safe, with limited adverse events and
      minimal drug-drug interactions in comparison to the other regimens. Therefore,
      these agents are strongly recommended when dealing with elderly patients
      suffering from an invasive form of Candida infection. 

PMID- 24043936
TI  - Comparative efficacy of aclidinium versus glycopyrronium and tiotropium, as
      maintenance treatment of moderate to severe COPD patients: a systematic review
      and network meta-analysis.
AB  - BACKGROUND: Aclidinium bromide is a new long-acting muscarinic antagonist (LAMA)
      indicated for maintenance bronchodilator treatment of chronic obstructive
      pulmonary disease (COPD). The efficacy of aclidinium was compared with tiotropium
      and glycopyrronium, using a network meta-analysis (NMA) of randomized controlled
      trials (RCTs) in moderate-to-severe COPD patients. METHODS: A systematic review
      was performed to identify RCTs evaluating aclidinium 400 MUg twice daily (BID),
      glycopyrronium 50 MUg once daily (OD), tiotropium 18 MUg OD, or tiotropium 5 MUg
      OD in adults with moderate-to-severe COPD. The outcomes of interest were: trough
      forced expiratory volume in 1 second (FEV1); St George's Respiratory
      Questionnaire (SGRQ) total score and proportion of patients achieving >=4 unit
      change; Transition Dyspnea Index (TDI) focal score and proportion of patients
      achieving >=1 point change. The results were synthesized by means of a Bayesian
      NMA. RESULTS: Twenty-one studies (22,542 patients) were included: aclidinium 400
      MUg BID (three studies); tiotropium 5 MUg OD (three studies); tiotropium 18 MUg
      OD (13 studies); and glycopyrronium 50 MUg OD (two studies). Regarding trough
      FEV1 at 24 weeks, aclidinium demonstrated comparable efficacy to tiotropium 5 MUg
      (difference in change from baseline [CFB]), (0.02 L [95% credible interval CrI 
      0.05, 0.09]); tiotropium 18 MUg (0.02 L [95% CrI -0.05, 0.08]); and
      glycopyrronium (0.00 L [95% CrI -0.07, 0.07]). Aclidinium resulted in higher
      improvement in SGRQ score at 24 weeks, compared to tiotropium 5 MUg (difference
      in CFB, -2.44 [95% CrI -4.82, -0.05]); and comparable results to tiotropium 18
      MUg (-1.80 [95% CrI -4.52, 0.14]) and glycopyrronium (-1.52 [95% CrI -4.08,
      1.03]). Improvements in TDI score were comparable for all treatments. CONCLUSION:
      Maintenance treatment with aclidinium 400 MUg BID is expected to produce similar
      improvements in lung function, health-related quality of life, and dyspnea
      compared to tiotropium 5 MUg OD; tiotropium 18 MUg OD; and glycopyrronium 50 MUg
      OD.

PMID- 24043937
TI  - Nanotoxicological evaluation of oxidative responses in rat nephrocytes induced by
      cadmium.
AB  - The aim of this study was to investigate the interaction of cadmium chloride with
      mineral elements in rat nephrocytes in terms of the biosynthesis of
      nanocomplexes. The results show that selenium supplementation enhanced cadmium
      accumulation in kidneys. Analysis of the fluorescence revealed an increase in red
      fluorescence in the kidneys of rats co-exposed to cadmium and selenium.
      Interestingly, X-ray diffraction measurements carried out on kidney fractions of
      co-exposed rats point to the biosynthesis of cadmium selenide and/or sulfide
      nanoparticles (about 62 nm in size). Oxidative stress assays showed the ability
      of selenium to reduce lipid peroxidation and to restore glutathione peroxidase
      and superoxide dismutase activity in kidneys. Hence, cadmium complexation with
      selenium and sulfur at a nanoscale level could reduce oxidative stress induced by
      cadmium in kidneys. 

PMID- 24043938
TI  - Prevalence of neurological disorders in Al Quseir, Egypt: methodological aspects.
AB  - Methodology and strategy play a very important role in epidemiological studies.
      Determination of the study area, geographical features, facilities, difficulties,
      and key personnel from the same area are important factors for successful
      methodology. Over 31 months (July 1, 2009 to January 31, 2012), a screening and
      an examination survey were carried out to ascertain the prevalence of epilepsy,
      stroke, dementia, cerebellar ataxia, migraine, cerebral palsy, Parkinsonism,
      chorea, athetosis, dystonia, trigeminal neuralgia, Bell's palsy, multiple
      sclerosis, spinal cord disorders, and attention deficit hyperactivity disorders
      in Al Quseir, Red Sea Governorate, Egypt. A total of 33,285 people were screened
      by three neurologists in a door-to-door manner, including every door, using a
      standardized Arabic questionnaire to detect any subject with a neurological
      disorder. The methodological aspects of this project were carried out through
      eight phases: (1) data collection; (2) preparation; (3) screening; (4) case
      ascertainment; (5) investigations; (6) classifications; (7) data entry; and (8)
      statistics and tabulations. The results of this study reveal that the total
      prevalence of neurological disorders in Al Quseir was 4.6% and higher among
      females (5.2%) than males (3.9%). The highest prevalence was recorded in the
      elderly population (60+ years [8.0%]) and among the age group 18-39 years (5.4%).

PMID- 24043939
TI  - Predicting acute side effects of stimulant medication in pediatric attention
      deficit/hyperactivity disorder: data from quantitative electroencephalography,
      event-related potentials, and a continuous-performance test.
AB  - BACKGROUND: The aim of this study was to search for predictors of acute side
      effects of stimulant medication in pediatric attention deficit/hyperactivity
      disorder (ADHD), emphasizing variables from quantitative electroencephalography
      (QEEG), event-related potentials (ERPs), and behavior data from a visual
      continuous-performance test (VCPT). METHODS: Seventy medication-naive ADHD
      patients aged 7-16 years were tested with QEEG, including a go/no-go task
      condition (VCPT) from which behavior data and ERPs were extracted, followed by a
      systematic trial on stimulant medication lasting at least 4 weeks. Based on data
      from rating scales and interviews, two psychologists who were blind to the
      QEEG/ERP test results independently rated the patients as having no or small side
      effects (n = 37) or troublesome side effects (n = 33). We determined if the side
      effects were related to sex, age, IQ, ADHD subtype, comorbidities, clinical
      outcome, and variables in QEEG, ERPs, and VCPT. RESULTS: There was a moderate
      negative correlation between clinical outcome and side effects. Three variables
      were significantly associated with side effects in a multivariate logistic
      regression analysis. In the ERP independent component - contingent negative
      variation - which reflected action preparation and time evaluation, patients with
      high amplitudes (close to normal values) experienced more side effects than
      patients with lower amplitudes. A faster-than-normal reaction time in VCPT was
      associated with side effects, as was a high amplitude in an early ERP component
      (early visual independent component), reported to be influenced by attention,
      perceptual sensitivity, and anxiety. CONCLUSION: The group with troublesome side
      effects had normal action-preparation electrical brain activity, a faster-than
      normal reaction time, and an increased level of anxiety (measured by ERP)
      compared with the no side-effects group.

PMID- 24043940
TI  - Safety of escitalopram in pregnancy: a case series.
AB  - BACKGROUND: The aim of this paper is to report maternal and neonatal outcomes in
      pregnant women treated with escitalopram during pregnancy and breastfeeding.
      METHODS: Women enrolled in the DEGRA Database at the Clinic of Affective
      Disorders in Pregnancy and Postpartum in Italy, treated during pregnancy with
      escitalopram and followed up throughout pregnancy, were included in this study.
      All patients provided written informed consent and the study was approved by the
      local ethics committee. Psychiatric diagnoses were assessed using the Structured
      Clinical Interview for DSM-IV (Diagnostic and Statistical Manual of Mental
      Disorders - Fourth Edition) Axis I Disorders and symptoms were assessed using the
      Hamilton Rating Scale for Depression (17 items) and Hamilton Rating Scale for
      Anxiety (14 items). Clinical and sociodemographic characteristics as well as
      maternal and neonatal outcomes were recorded. RESULTS: The case histories of
      seven pregnant women treated for depression and/or anxiety disorders with
      escitalopram were reported. Four women were also treated with benzodiazepines.
      All pregnancies were full-term and all newborns had normal Apgar scores. There
      were no major malformations or miscarriages following exposure to escitalopram.
      Mild withdrawal syndrome was reported only in a newborn who was also exposed to a
      benzodiazepine. Two infants exposed to escitalopram during breastfeeding did not
      show any health problems. CONCLUSION: Our experience with use of escitalopram in
      pregnant women did not reveal any maternal or neonatal concerns. However,
      considering the few cases analyzed and the paucity of published literature, no
      conclusions can be drawn on its safety profile in pregnancy and breastfeeding.

PMID- 24043941
TI  - The effect of eradicating Helicobacter pylori on idiopathic central serous
      chorioretinopathy patients.
AB  - PURPOSE: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on
      the remission of acute idiopathic central serous chorioretinopathy (ICSCR). STUDY
      DESIGN: A prospective, randomized, placebo-controlled study of 53 participants.
      MAIN OUTCOME MEASURE: Twenty-seven acute ICSCR patients tested positive for H.
      pylori were given an eradication H. pylori therapy, and another 26 patients with
      the same diagnosis received matching placebo medication. All participants were
      tested for the following items: (1) disappearance rate of subretinal fluid (SRF);
      (2) best-corrected visual acuity (BCVA); and (3) central retinal sensitivity at
      baseline, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after treatment. The difference
      between the two groups was analyzed by PASW statistics version 18.0. RESULTS: At
      each follow-up, the disappearance rate of SRF in the active treatment group
      seemed slightly better than in the control group, but no statistically
      significant differences were observed (P > 0.05 at each follow-up). The BCVA
      between the two groups also did not demonstrate statistically significant
      differences (P > 0.05 at each follow-up). Unlike the BCVA and the disappearance
      rate of SRF, we compared the change in central retinal sensitivity at 12 weeks
      after treatment; a statistical difference was observed (P = 0.042). CONCLUSION:
      Our findings suggested that H. pylori eradication does not improve BCVA and the
      disappearance rate of SRF, but it could improve the central retinal sensitivity
      in acute ICSCR patients. We recommend that chronic ICSCR patients and more
      sensitive methods for H. pylori diagnosis should be involved in evaluating the
      effect of H. pylori eradication.

PMID- 24043942
TI  - Increased burden and severity of metabolic syndrome and arterial stiffness in
      treatment-naive HIV+ patients from Cameroon.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) and its therapy are associated
      with increased aortic stiffness and metabolic syndrome (MetS) phenotype in
      Caucasian patients. We hypothesized that, independently of antiretroviral
      therapy, HIV infection in native black African patients is associated with
      increased burden of cardiometabolic risk factors that may accelerate arterial
      structural damage and translate into increased aortic stiffness. PATIENTS AND
      METHODS: Ninety-six apparently healthy Cameroonian subjects (controls) were
      compared to 108 untreated Cameroonian HIV+ patients (HIV-UT) of similar age. In
      each participant, pulse wave velocity (Complior), aortic augmentation index
      (SphygmoCor), brachial blood pressure (Omron 705 IT), fasting plasma glucose
      (FPG), and lipids were recorded, as well as the prevalence and severity of MetS,
      based on the American Heart Association/National Heart, Lung, and Blood Institute
      score >=3/5. RESULTS: Prevalence of impaired fasting glucose (FPG 100-125 mg . dL
      1) and of diabetes (FPG > 125 mg . dL-1) was higher in HIV-UT than in controls
      (47% versus 27%, and 26% versus 1%, respectively; both P < 0.01). Fasting
      triglycerides and the atherogenic dyslipidemia ratio were significantly higher in
      HIV-UT than in controls. Hypertension prevalence was high and comparable in both
      groups (41% versus 44%, respectively; not significant). HIV-UT patients exhibited
      a twice-higher prevalence of MetS than controls (47% versus 21%; P = 0.02). Age-
      and sex-adjusted pulse wave velocity was higher in HIV-UT than in controls (7.5
      +/- 2.2 m/s versus 6.9 +/- 1.7 m/s, respectively; P = 0.02), whereas aortic
      augmentation index was significantly lower (6% +/- 4% versus 8% +/- 7%,
      respectively; P = 0.01). CONCLUSION: Similar to Caucasian populations, native
      Cameroonian HIV-UT patients showed a higher prevalence of MetS and its phenotype,
      associated with increased aortic stiffness, an early marker of atherosclerosis.

PMID- 24043943
TI  - Serum calcium levels are not associated with coronary heart disease.
AB  - BACKGROUND: Numerous studies have reported that low calcium intake is related to
      a higher prevalence of cardiovascular disease. However, the relationship between
      serum calcium and coronary heart disease is unclear. The purpose of this study
      was to compare serum calcium levels in patients with coronary heart disease and
      those in healthy individuals. METHODS: This retrospective, case-control study
      conducted in the People's Republic of China comprised 380 cases and 379 controls.
      Serum calcium levels, blood lipids, and anthropometric measurements were measured
      in both groups. The Student's unpaired t-test or Chi-square test was used to
      compare differences between cases and controls. Pearson's partial correlation
      coefficient was used to determine the association between serum calcium, blood
      lipids, and blood pressure in both groups. RESULTS: Our results indicate that the
      average level of serum calcium in cases was higher than in controls. Serum
      calcium levels showed no correlation with any parameter except for triglycerides
      in either group. CONCLUSION: Overall, these data suggest that serum calcium has
      no influence on coronary heart disease or triglyceride levels in the general
      population.

PMID- 24043944
TI  - Lumbar paravertebral blockade as intractable pain management method in palliative
      care.
AB  - Optimal symptoms control in advanced cancer disease, with refractory to
      conventional pain treatment, needs an interventional procedure. This paper
      presents coadministration of local anesthetic (LA) via paravertebral blockade
      (PVB) as the alternative to an unsuccessful subcutaneous fentanyl pain control in
      a 71-year old cancer patient with pathological fracture of femoral neck, bone
      metastases, and contraindications to morphine. Bupivacaine in continuous infusion
      (0.25%, 5 mL . hour(-1)) or in boluses (10 mL of 0.125%-0.5% solution), used for
      lumbar PVB, resulted in pain relief, decreased demand for opioids, and led to
      better social interactions. The factors contributing to an increased risk of
      systemic toxicity from LA in the patient were: renal impairment; heart failure;
      hypoalbuminemia; hypocalcemia; and a complex therapy with possible drug-drug
      interactions. These factors were taken into consideration during treatment.
      Bupivacaine's side effects were absent. Coadministered drugs could mask LA's
      toxicity. Elevated plasma alpha1-acid glycoprotein levels were a protective
      factor. To evaluate the benefit-risk ratio of the PVB treatment in boluses and in
      constant infusion, bupivacaine serum levels were determined and the drug plasma
      half-lives were calculated. Bupivacaine's elimination was slower when
      administered in constant infusion than in boluses (t1/2 = 7.80 hours versus 2.64
      hours). Total drug serum concentrations remained within the safe ranges during
      the whole treatment course (22.9-927.4 ng mL(-1)). In the case presented, lumbar
      PVB with bupivacaine in boluses (<= 137.5 mg . 24 hours(-1)) was an easy to
      perform, safe, effective method for pain control. Bupivacaine in continuous
      infusion (<=150 mg . 12 hours(-1)) had an acceptable risk-benefits ratio, but was
      ineffective. 

PMID- 24043945
TI  - Emerging treatment options for recurrent ovarian cancer: the potential role of
      olaparib.
AB  - Olaparib has shown promising anticancer activity as a single agent in the
      treatment and maintenance of recurrent ovarian cancer in early clinical trials,
      but it is far from standard therapy. This article outlines the problem of
      relapsed ovarian cancer and the mechanisms of poly(ADP-ribose) polymerase
      inhibitors and reviews the recent literature pertaining to olaparib in ovarian
      cancer. 

PMID- 24043947
TI  - Friend or foe: emerging role of nuclear factor kappa-light-chain-enhancer of
      activated B cells in cell senescence.
AB  - The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB)
      proteins are a family of ubiquitously expressed transcription factors that
      regulate the response to cellular stress. They mediate innate and adaptive
      immunity through the initiation of an inflammatory response to pro-inflammatory
      signals. The role of persistent inflammation in aiding tumor development has led
      to the NF-kappaB family of transcription factors being strongly implicated in
      promoting cancer. However, recent studies have now revealed that NF-kappaB can
      also function as a tumor suppressor through the induction of cellular senescence.
      Cellular senescence is a stable cell cycle arrest that normal cells undergo in
      response to a variety of intrinsic and extrinsic stimuli including: progressive
      telomere shortening, changes in telomeric structure, or other forms of genotoxic
      stress. Senescence can compromise tissue repair and regeneration, contributing to
      tissue and organismal aging via the accumulation of senescent cells, depletion of
      stem/progenitor cells and secretion of an array of inflammatory cytokines,
      chemokines, and matrix metalloproteinases. Senescence can also lead to the
      removal of potentially cancerous cells, thereby acting as a potent tumor
      suppressor mechanism. Herein, we review the evidence indicating a role for NF
      kappaB in tumor suppression via cellular senescence and suggest that depending
      upon the subunit expressed, the biological context, and the type and intensity of
      the signal, NF-kappaB can indeed promote senescence growth arrest. 

PMID- 24043946
TI  - Targeting cancer stem cells: emerging role of Nanog transcription factor.
AB  - The involvement of stemness factors in cancer initiation and progression has
      drawn much attention recently, especially after the finding that introducing four
      stemness factors in somatic cells is able to reprogram the cells back to an
      embryonic stem cell-like state. Following accumulating data revealing abnormal
      elevated expression levels of key stemness factors, like Nanog, Oct4, and Sox2,
      in several types of cancer stem cells; the importance and therapeutic potential
      of targeting these stemness regulators in cancers has turned to research focus.
      Nanog determines cell fate in both embryonic and cancer stem cells; activating
      Nanog at an inappropriate time would result in cancer stem cells rather than
      normal pluripotent stem cells or differentiated somatic cells. Upregulated Nanog
      is correlated with poor survival outcome of patients with various types of
      cancer. The discoveries of downstream regulatory pathways directly or indirectly
      mediated by Nanog indicate that Nanog regulates several aspects of cancer
      development such as tumor cell proliferation, self-renewal, motility, epithelial
      mesenchymal transition, immune evasion, and drug-resistance, which are all
      defined features for cancer stem cells. The current review paper illustrates the
      central role of Nanog in the regulatory networks of cancer malignant development
      and stemness acquirement, as well as in the communication between cancer cells
      and the surrounding stroma. Though a more defined model is needed to test the
      therapeutic efficacy of targeting Nanog as a cancer treatment method, current
      animal experiments using siNanog or shNanog have shown the promising therapeutic
      potential of Nanog targeting in several types of cancer. 

PMID- 24043948
TI  - How to detour Treg cells in T cell-based antitumor immune therapy.
AB  - T cell-based antitumor immune therapy which occupies the boosting area of
      translational medicine research is capable of eradicating some kinds of tumors
      that are in late stages. However, the effectiveness of adoptive cell transfer
      treatment varies among the different clinical trials, while the safety of cells
      is still uncertain for some patients. All these phenomena provoke us to ask
      whether the instability of T cell-based antitumor immune therapy is due to immune
      modulation function of Treg cells in the tumor microenvironment and the
      peripheral circulation. Some successful Treg-targeting treatments in clinical
      trials provide the inspiration for subtle modulation of Treg cells in future
      cancer immunotherapies. We hypothesized that Treg cells may somehow sense the
      abundance of peripheral immune effector cells, and maintain the shifted tumor
      bearing homeostasis of the immune system. Killer cells infused in adoptive cell
      transfer therapy may be monitored and spontaneously downregulated by Treg cells.
      Further studies are required to develop more effective combinations of
      immunotherapy with conventional chemo/radiotherapy in the modulation of immune
      suppressive cells. 

PMID- 24043950
TI  - Acute hemorrhagic edema of infancy: a worrisome presentation, but benign course.
AB  - Acute hemorrhagic edema of infancy (AHEI) is a benign type of leukocytoclastic
      vasculitis. It is a benign phenomenon although it manifests with fever, large
      palpable purpuric skin lesions, and edema. The presentation of AHEI can often
      resemble that of Henoch-Schonlein purpura. Since AHEI is a self-limited disease,
      conservative management is the most commonly followed approach. Our patient had
      complete resolution of AHIE without medical treatment. 

PMID- 24043951
TI  - The effectiveness of massage therapy for the treatment of nonspecific low back
      pain: a systematic review of systematic reviews.
AB  - INTRODUCTION: The last decade has seen a growth in the utilization of
      complementary and alternative medicine therapies, and one of the most popular and
      sought-after complementary and alternative medicine therapies for nonspecific low
      back pain is massage. Massage may often be perceived as a safe therapeutic
      modality without any significant risks or side effects. However, despite its
      popularity, there continues to be ongoing debate on the effectiveness of massage
      in treating nonspecific low back pain. With a rapidly evolving research evidence
      base and access to innovative means of synthesizing evidence, it is time to
      reinvestigate this issue. METHODS: A systematic, step-by-step approach,
      underpinned by best practice in reviewing the literature, was utilized as part of
      the methodology of this umbrella review. A systematic search was conducted in the
      following databases: Embase, MEDLINE, AMED, ICONDA, Academic Search Premier,
      Australia/New Zealand Reference Centre, CINAHL, HealthSource, SPORTDiscus,
      PubMed, The Cochrane Library, Scopus, Web of Knowledge/Web of Science, PsycINFO,
      and ProQuest Nursing and Allied Health Source, investigating systematic reviews
      and meta-analyses from January 2000 to December 2012, and restricted to English
      language documents. Methodological quality of included reviews was undertaken
      using the Centre for Evidence Based Medicine critical appraisal tool. RESULTS:
      Nine systematic reviews were found. The methodological quality of the systematic
      reviews varied (from poor to excellent) although, overall, the primary research
      informing these systematic reviews was generally considered to be weak quality.
      The findings indicate that massage may be an effective treatment option when
      compared to placebo and some active treatment options (such as relaxation),
      especially in the short term. There is conflicting and contradictory findings for
      the effectiveness of massage therapy for the treatment of nonspecific low back
      pain when compared against other manual therapies (such as mobilization),
      standard medical care, and acupuncture. CONCLUSION: There is an emerging body of
      evidence, albeit small, that supports the effectiveness of massage therapy for
      the treatment of non-specific low back pain in the short term. Due to common
      methodological flaws in the primary research, which informed the systematic
      reviews, recommendations arising from this evidence base should be interpreted
      with caution.

PMID- 24043949
TI  - Notch signaling: targeting cancer stem cells and epithelial-to-mesenchymal
      transition.
AB  - Notch signaling is an evolutionarily conserved pathway involved in cell fate
      control during development, stem cell self-renewal, and postnatal tissue
      differentiation. Roles for Notch in carcinogenesis, the biology of cancer stem
      cells, tumor angiogenesis, and epithelial-to-mesenchymal transition (EMT) have
      been reported. This review describes the role of Notch in the "stemness" program
      in cancer cells and in metastases, together with a brief update on the Notch
      inhibitors currently under investigation in oncology. These agents may be useful
      in targeting cancer stem cells and to reverse the EMT process. 

PMID- 24043952
TI  - Lymphangiopathy in neurofibromatosis 1 manifesting with chylothorax, pericardial
      effusion, and leg edema.
AB  - BACKGROUND: This case report documents the affliction of the lymph vessels as a
      phenotypic feature of neurofibromatosis-1 (NF-1). METHODOLOGY: Routine
      transthoracic echocardiography, computed tomography scan of the thorax, magnetic
      resonance angiography of the renal arteries, and conventional digital subtraction
      angiography were applied. Comprehensive NF-1 mutation analysis was carried out by
      fluorescence in situ hybridization analysis, long-range reverse transcriptase
      polymerase chain reaction, and multiple-ligation probe assay. All other
      investigations were performed using routine, well-established techniques.
      RESULTS: The subject is a 34-year-old, half-Chinese male; NF-1 was suspected at
      age 15 years for the first time. His medical history included preterm birth, mild
      facial dysmorphism, "cafe au lait" spots, subcutaneous and paravertebral
      fibromas, multifocal tachycardia, atrial fibrillation, and heart failure in early
      infancy. Noncalcified bone fibromas in the femur and tibia were detected at age 8
      years. Surgical right leg lengthening was carried out at age 11 years. Bilateral
      renal artery stenosis, stenosis and aneurysm of the superior mesenteric artery,
      and an infrarenal aortic stenosis were detected at age 15 years. Leg edema and
      ectasia of the basilar artery were diagnosed at age 18 years. After an episode
      with an erysipela at age 34 years, he developed pericardial and pleural effusion
      during a 4-month period. Stenosis of the left subclavian vein at the level of
      thoracic duct insertion was detected. After repeated pleural punctures, pleural
      effusion was interpreted as chylothorax. Reduction of lymph fluid production by
      diet and injection of talcum into the pleural cavity had a long-term beneficial
      effect on the chylothorax. Leg edema and chylothorax were attributed to
      affliction of the lymph vessels by the NF-1. DISCUSSION: Lymphangiopathy
      resulting in impaired lymph fluid flow and sequestration of lymph fluid into the
      pleural sinus and the legs may be a rare phenotypic feature of NF-1.

PMID- 24043953
TI  - Evaluation of the Bonapace Method: a specific educational intervention to reduce
      pain during childbirth.
AB  - OBJECTIVE: As pain during childbirth is very intense, several educational
      programs exist to help women prepare for the event. This study evaluates the
      efficacy of a specific pain management program, the Bonapace Method (BM), to
      reduce the perception of pain during childbirth. The BM involves the father, or a
      significant partner, in the use of several pain control techniques based on three
      neurophysiological pain modulation models: (1) controlling the central nervous
      system through breathing, relaxation, and cognitive structuring; (2) using non
      painful stimuli as described in the Gate Control Theory; and (3) recruiting
      descending inhibition by hyperstimulation of acupressure trigger points. METHODS:
      A multicenter case control study in Quebec on pain perception during labor and
      delivery compared traditional childbirth training programs (TCTPs) and the BM.
      Visual analog scales were used to measure pain perception during labor. In all,
      25 women (TCTP: n = 12; BM: n = 13) successfully reported their perceptions of
      pain intensity and unpleasantness every 15 minutes. RESULTS: A POSITIVE
      CORRELATION BETWEEN THE PROGRESSION OF LABOR AND PAIN WAS FOUND (PAIN INTENSITY:
      P < 0.01; pain unpleasantness: P < 0.01). When compared to TCTP, the BM showed an
      overall significant lower pain perception for both intensity (45%; P < 0.01) and
      unpleasantness (46%; P < 0.01). CONCLUSION: These significant differences in pain
      perception between TCTP and the BM suggest that the emphasis on pain modulation
      models and techniques during labor combined with the active participation of a
      partner in BM are important variables to be added to the traditional childbirth
      training programs for childbirth pain management.

PMID- 24043954
TI  - Association between vitamin D insufficiency and adverse pregnancy outcome: global
      comparisons.
AB  - BACKGROUND: Vitamin D insufficiency has been associated with a number of adverse
      pregnancy outcomes, and has been recognized as a public health concern. AIM: The
      objective of this study was to determine the impact of vitamin D deficiency on
      maternal complications like gestational diabetes mellitus (GDM), anemia, iron
      deficiency, and preeclampsia among pregnant women. SUBJECTS AND METHODS: This was
      a cohort study undertaken at antenatal clinics at the Women's Hospital of Hamad
      Medical Corporation in Doha. A total of 2,487 Arab pregnant women above 24 weeks'
      gestation with any maternal complication were approached, and 1,873 women (75.3%)
      consented to participate in the study. Data on sociodemographic and clinical
      characteristics by interview and biochemistry parameters were retrieved from
      medical records. Multivariate logistic regression analysis was performed to
      determine the associated risk factors. RESULTS: Of the studied pregnant women,
      nearly half of them had vitamin D deficiency (48.4%). Younger women below 30
      years old (43.2%, P = 0.032), housewives (65.3%, P = 0.008), and those on low
      monthly household incomes (QR5,000-9,999) (49.2%, P = 0.03) were significantly
      more likely to have lower vitamin D compared with those who had sufficient
      vitamin D levels. Exposure to sunlight (63.4%, P = 0.05), daily physical activity
      (64.4%, P = 0.05), and vitamin D supplement intake (89.7%, P < 0.001) were
      significantly lower in deficient pregnant women. In the study sample of pregnant
      women, 13.9% had GDM, 11.5% had anemia, 8.6% had iron deficiency, and 6.9% had
      preeclampsia. Severe vitamin D deficiency was significantly higher in pregnant
      women with GDM (16.5% vs 11%), anemia (17.1% vs 11%), iron deficiency (18.5% vs
      11.2%), and preeclampsia (19.8% vs 11.4%) when compared to the uncomplicated
      group. Socioeconomic status was low in pregnant women with complications like
      GDM, anemia, iron deficiency, and pre-eclampsia. Pregnancy complications like GDM
      (52.7%), anemia (53.2%), iron deficiency (55.6%), and preeclampsia (51.9%) were
      higher in Qataris. Also, GDM (66.2%), anemia (66.2%), iron deficiency (68.5%),
      and preeclampsia (58.1%) were observed more commonly among housewives compared to
      working women. Obesity was significantly more common in pregnant women with GDM
      (41.5%) and preeclampsia (41.1%). CONCLUSION: The study findings revealed that
      maternal vitamin D deficiency in pregnancy is significantly associated with
      elevated risk for GDM, anemia, and preeclampsia. The risk of vitamin D deficiency
      was higher in Qataris, housewives and those with low monthly household income.

PMID- 24043955
TI  - Triptolide induces lysosomal-mediated programmed cell death in MCF-7 breast
      cancer cells.
AB  - BACKGROUND: Breast cancer is a major cause of death; in fact, it is the most
      common type, in order of the number of global deaths, of cancer in women
      worldwide. This research seeks to investigate how triptolide, an extract from the
      Chinese herb Tripterygium wilfordii Hook F, induces apoptosis in MCF-7 human
      breast cancer cells. Accumulating evidence suggests a role for lysosomal
      proteases in the activation of apoptosis. However, there is also some controversy
      regarding the direct participation of lysosomal proteases in activation of key
      apoptosis-related caspases and release of mitochondrial cytochrome c. In the
      present study, we demonstrate that triptolide induces an atypical, lysosomal
      mediated apoptotic cell death in MCF-7 cells because they lack caspase-3.
      METHODS: MCF-7 cell death was characterized via cellular morphology, chromatin
      condensation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
      colorimetric cell growth inhibition assay and the expression levels of
      proapoptotic proteins. Acridine orange and LysoTracker(r) staining were performed
      to visualize lysosomes. Lysosomal enzymatic activity was monitored using an acid
      phosphatase assay and western blotting of cathepsin B protein levels in the
      cytosolic fraction, which showed increased enzymatic activity in drug-treated
      cells. RESULTS: These experiments suggest that triptolide-treated MCF-7 cells
      undergo atypical apoptosis and that, during the early stages, lysosomal enzymes
      leak into the cytosol, indicating lysosomal membrane permeability. CONCLUSION:
      Our results suggest that further studies are warranted to investigate
      triptolide's potential as an anticancer therapeutic agent.

PMID- 24043956
TI  - Ethical aspects of obstetric care: expectations and experiences of patients in
      South East Nigeria.
AB  - BACKGROUND: Medical ethics is not given due priority in obstetric care in many
      developing countries, and the extent to which patients value compliance with
      ethical precepts is largely unexplored. OBJECTIVE: To describe the expectations
      and experiences of obstetric patients in South East Nigeria with respect to how
      medical ethics principles were adhered to during their care. METHODS: This was a
      cross-sectional, questionnaire-based study involving parturient women followed in
      three tertiary hospitals in South East Nigeria. RESULTS: A total of 1,112 women
      were studied. The mean age of respondents was 29.7 +/- 4.1 years. Approximately
      98% had at least secondary education. Ninety-six percent considered ethical
      aspects of care as important. On the average, over 75% of patients expected their
      doctors to comply with the different principles of medical ethics and
      specifically, more than 76% of respondents expected their doctors to comply with
      ethical principles related to information and consent during their antenatal and
      delivery care. There was a statistically significant difference between the
      proportions of women who expected compliance of doctors with ethical principles
      and those who did not (P < 0.001). Multivariate analysis showed that increasing
      levels of skilled occupation (odds ratio [OR] 9.35, P < 0.001), and residence in
      urban areas (OR 2.41, P < 0.001) increased the likelihood of patients expecting
      to be informed about their medical conditions and their opinions being sought.
      Although the self-reported experiences of patients concerning adherence to
      ethical principles by doctors were encouraging, experiences fell short of
      expectations, as the level of expectation of patients was significantly higher
      than the level of observed compliance for all the principles of medical ethics.
      CONCLUSION: The level of practice of medical ethics principles by doctors during
      obstetric care in South East Nigeria was encouraging but still fell short of the
      expectations of patients. It is recommended that curriculum-based training of
      doctors and medical students should be implemented, and hospital policy makers
      should do more to promote ethical aspects of care, by providing official written
      guidelines for adherence to medical ethical principles during obstetric care.

PMID- 24043957
TI  - Ectopic lingual thyroid with vascular anomalies.
AB  - BACKGROUND: Lingual thyroid represents 90% of ectopic thyroid tissue
      localizations. The first case was described by Hickman in 1869. An ectopic
      thyroid is often asymptomatic, but pathological or physiological conditions
      inducing hyperproduction of thyroid-stimulating hormone can lead an ectopic
      thyroid to become symptomatic. Treatment of the symptomatic ectopic thyroid can
      be medical, with hormone-suppressing therapy, or surgical. CASE PRESENTATION: A
      17-year-old female presented to our outpatient clinic complaining of a sensation
      of a lump in her throat. Ear, nose, and throat (ENT) examination identified a
      swelling of the base of the tongue in the glossoepiglottic area. Thyroid
      scintigraphy showed a single contrast enhancement in the sublingual region,
      instead of in the normal anatomical position of the thyroid. She was treated
      surgically after failed hormone-suppressing therapy. An arteriography performed
      before the surgery showed vascular anomalies and was useful in surgical planning.
      CONCLUSION: Recognition of vascular anomalies in an ectopic thyroid is
      fundamental before surgical planning, therefore, accurate radiological study of
      the vasculature should always be planned before surgical treatment of this
      disease.

PMID- 24043958
TI  - Reviews of botulinum toxin products in aesthetic use must be accurate, clear and
      avoid speculation.

PMID- 24043959
TI  - Power port contrast medium flushing and trapping: impact of temperature, an in
      vitro experimental study.
AB  - PURPOSE: The use of totally implantable venous access devices (TIVADs) certified
      as "high pressure resistant" or "power port" has begun to spread worldwide as a
      safe procedure for power contrast injection. Owing to the thermo-rheological
      properties of the contrast media, the primary aim of this work is to present an
      in vitro experimental impact study concerning the impact of the temperature level
      on flushing efficiency after contrast medium injection. Moreover, we report
      experimental data that confirms the role of needle bevel orientation. The
      secondary aim is to answer the following questions: Is there significant device
      contrast medium trapping after contrast medium injection? Is saline flushing
      efficient? And, finally, is it safe to inject contrast medium through an
      indwelled port catheter? RESULTS: The experimental results show that in addition
      to hydrodynamics, temperature is a key parameter for the efficiency of device
      flushing after contrast medium injection. It appears that this is the case when
      the cavity is incompletely rinsed after three calibrated flushing volumes of 10
      mL saline solution, even by using the Huber needle bevel opposite to the port
      exit. This leads to a potentially important trapped volume of contrast medium in
      the port, and consequently to the possibility of subsequent salt precipitates and
      long term trisubstituted benzene nuclei delivery that might impair the solute
      properties, which may be further injected via the power port later on.
      CONCLUSION: We thus suggest, in TIVADS patients, the use of a temporary
      supplementary intravenous line rather than the port to perform contrast medium
      injections in daily radiology routine practice.

PMID- 24043960
TI  - Spanish version of the Thought-Action Fusion Questionnaire and its application in
      eating disorders.
AB  - PURPOSE: The aims of the study were to analyze the psychometric properties of the
      Spanish version of the Thought-Action Fusion Questionnaire (TAF-SP), as well as
      to determine its validity by evaluating the relationship of the TAF-SP to
      different instruments. PATIENTS AND METHODS: TWO GROUPS WERE STUDIED: one
      comprising 146 patients with eating disorders; and another a group of 200
      students. RESULTS: THREE FACTORS WERE OBTAINED: TAF-Moral; TAF-Likelihood-others;
      and TAF-Likelihood-oneself. The internal consistency of the TAF-SP was determined
      by means of Cronbach's alpha coefficient, with values ranging between 0.84-0.95.
      The correlations with other instruments refected adequate validity. The three
      factor structure was tested by means of a linear structural equation model, and
      the structure fit satisfactorily. Differences in TAF-SP scores between the
      diagnostic subgroups were also analyzed. CONCLUSION: The TAF-SP meets the
      psychometric requirements for measuring thought-action fusion and shows adequate
      internal consistency and validity.

PMID- 24043961
TI  - Clinical image evaluation of film mammograms in Korea: comparison with the ACR
      standard.
AB  - OBJECTIVE: The goal of this study is to compare the overall quality of film
      mammograms taken according to the Korean standards with the American College of
      Radiology (ACR) standard for clinical image evaluation and to identify means of
      improving mammography quality in Korea. MATERIALS AND METHODS: Four hundred and
      sixty eight sets of film mammograms were evaluated with respect to the Korean and
      ACR standards for clinical image evaluation. The pass and failure rates of
      mammograms were compared by medical facility types. Average scores in each
      category of the two standards were evaluated. Receiver operating characteristic
      curve analysis was used to identify an optimal Korean standard pass mark by
      taking the ACR standard as the reference standard. RESULTS: 93.6% (438/468) of
      mammograms passed the Korean standard, whereas only 80.1% (375/468) passed the
      ACR standard (p < 0.001). Non-radiologic private clinics had the lowest pass rate
      (88.1%: Korean standard, 71.8%: ACR standard) and the lowest total score (76.0)
      by the Korean standard. Average scores of positioning were lowest (19.3/29 by the
      Korean standard and 3.7/5 by the ACR standard). A cutoff score of 77.0 for the
      Korean standard was found to correspond to a pass level when the ACR standard was
      applied. CONCLUSION: We suggest that tighter regulations, such as, raising the
      Korean pass mark, subtracting more for severe deficiencies, or considering a very
      low scores in even a single category as failure, are needed to improve the
      quality of mammography in Korea.

PMID- 24043962
TI  - Band-like interposing fat along large vessels: ultrasonographic pseudolesions of
      the breast.
AB  - OBJECTIVE: The aim of this study is to evaluate the clinical characteristics and
      ultrasonographic findings of band-like interposing fat as well as to identify
      additional approaches for its diagnosis. MATERIALS AND METHODS: This study
      included 26 confirmed cases of band-like interposing fat from June 2008 to June
      2010. A retrospective analysis was performed to evaluate the clinical
      characteristics and ultrasonographic findings in these cases. Five radiologists
      analyzed the ultrasonographic findings, which correlated with the mammographic
      and MRI findings when available, according to Breast Imaging Reporting and Data
      System classification. RESULTS: None of the 26 patients had any symptoms. In
      92.3% of the patients, the lesion was located in the upper outer quadrant of the
      breast. The mean distance of the lesion from the nipple was 2.4 +/- 0.7 cm (1.1
      4.5). The mean depth of the lesion from the skin was 1.3 +/- 0.3 cm (0.8-2.1).
      The mean maximal length of the lesion was 0.8 +/- 0.4 cm (0.3-1.8). The following
      were the most frequent ultrasonographic findings of lesions: irregular shape, not
      parallel orientation, indistinct margins, abrupt interface, hypoechogenicity, no
      posterior feature, no calcification, and presence of vascularity. The most
      frequent BI-RADS category was 4a. There were no suspicious findings on the
      mammography or MRI. CONCLUSION: Ultrasonographic findings may lead to
      misclassification of band-like interposing fat as a malignancy. A better
      understanding of the clinical and ultrasonographic characteristics of band-like
      interposing fat would facilitate its differentiation from a true mass.

PMID- 24043963
TI  - Isolated post-transplantation lymphoproliferative disease involving the breast
      and axilla as peripheral T-cell lymphoma.
AB  - Post-transplantation lymphoproliferative disorders (PTLDs) are a heterogeneous
      group of diseases that represent serious complications following
      immunosuppressive therapy for solid organ or hematopoietic-cell recipients. In
      contrast to B-cell PTLD, T-cell PTLD is less frequent and is not usually
      associated with Epstein Barr Virus infection. Moreover, to our knowledge,
      isolated T-cell PTLD involving the breast is extremely rare and this condition
      has never been reported previously in the literature. Herein, we report a rare
      case of isolated T-cell PTLD of the breast that occurred after a patient had been
      treated for allogeneic peripheral blood stem cell transplantation due to acute
      myeloblastic leukemia. 

PMID- 24043964
TI  - Primary breast amyloidosis presenting as microcalcifications only.
AB  - Amyloidosis is a rare disease characterized by the formation of pathological
      protein deposits in organs or tissues. It is typically a systemic disease which
      can occur in a localized form. Amyloidosis of the breast is uncommon. Common
      mammographic findings of breast amyloidosis are multiple nodules with or without
      calcifications. We report a case of primary localized breast amyloidosis
      presenting suspicious microcalcifications on mammography without associated
      masses. Mammography in a 72-year-old woman displayed multiple, linearly
      distributed, irregular and rod-like calcifications in the subareolar area of the
      left breast. The patient underwent surgical excision under mammo-guided needle
      localization and the pathology was confirmed to be breast amyloidosis. 

PMID- 24043965
TI  - Diagnosis of acute global myocarditis using cardiac MRI with quantitative t1 and
      t2 mapping: case report and literature review.
AB  - The diagnosis of myocarditis can be challenging given that symptoms, clinical
      exam findings, electrocardiogram results, biomarkers, and echocardiogram results
      are often non-specific. Endocardial biopsy is an established method for
      diagnosing myocarditis, but carries the risk of complications and false negative
      results. Cardiac magnetic resonance imaging (MRI) has become the primary non
      invasive imaging tool in patients with suspected myocarditis. Myocarditis can be
      diagnosed by using three tissue markers including edema, hyperemia/capillary
      leak, and necrosis/fibrosis. The interpretation of cardiac MR findings can be
      confusing, especially when the myocardium is diffusely involved. Using T1 and T2
      maps, the diagnosis of myocarditis can be made even in cases of global
      myocarditis with the help of quantitative analysis. We herein describe a case of
      acute global myocarditis which was diagnosed by using quantitative T1 and T2
      mapping. 

PMID- 24043966
TI  - Computed tomographic-guided radiofrequency ablation of recurrent or residual
      hepatocellular carcinomas around retained iodized oil after transarterial
      chemoembolization.
AB  - OBJECTIVE: To assess the clinical efficacy, safety, and risk factors influencing
      local tumor progression, following CT-guided radiofrequency ablation (RFA) of
      recurrent or residual hepatocellular carcinoma (HCC), around iodized oil
      retention. MATERIALS AND METHODS: Sixty-four patients (M : F = 51 : 13, 65.0 +/-
      8.2 years old) with recurrent or residual HCC (75 index tumors, size = 14.0 +/-
      4.6 mm) had been treated by CT-guided RFA, using retained iodized oil as markers
      for targeting. The technical success, technique effectiveness rate and
      complications of RFA were then assessed. On pre-ablative and immediate follow-up
      CT after RFA, we evaluated the size of enhancing index tumors and iodized oil
      retention, presence of abutting vessels, completeness of ablation of iodized oil
      retention, and the presence of ablative margins greater than 5 mm. Also, the time
      interval between transarterial chemoembolization and RFA was assessed. The
      cumulative local tumor progression rate was calculated using the Kaplan-Meier
      method, and the Cox proportional hazards model was adopted, to clarify the
      independent factors affecting local tumor progression. RESULTS: The technical
      success and technique effectiveness rate was 100% and 98.7%, respectively. Major
      complications were observed in 5.6%. The cumulative rates of local tumor
      progression at 1 and 2 years were 17.5% and 37.5%, respectively. In multivariate
      analyses, partial ablation of the targeted iodized oil retention was the sole
      independent predictor of a higher local tumor progression rate. CONCLUSION: CT
      guided RFA of HCC around iodized oil retention was effective and safe. Local
      tumor progression can be minimized by complete ablation of not only index tumors,
      but targeted iodized oil deposits as well.

PMID- 24043967
TI  - Acoustic radiation force impulse elastography for focal hepatic tumors:
      usefulness for differentiating hemangiomas from malignant tumors.
AB  - OBJECTIVE: The purpose of this study is to investigate whether acoustic radiation
      force impulse (ARFI) elastography with ARFI quantification and ARFI 2-dimensional
      (2D) imaging is useful for differentiating hepatic hemangiomas from malignant
      hepatic tumors. MATERIALS AND METHODS: One-hundred-and-one tumors in 74 patients
      were included in this study: 28 hemangiomas, 26 hepatocellular carcinomas (HCCs),
      three cholangiocarcinomas (CCCs), 20 colon cancer metastases and 24 other
      metastases. B-mode ultrasound, ARFI 2D imaging, and ARFI quantification were
      performed in all tumors. Shear wave velocities (SWVs) of the tumors and the
      adjacent liver and their SWV differences were compared among the tumor groups.
      The ARFI 2D images were compared with B-mode images regarding the stiffness,
      conspicuity and size of the tumors. RESULTS: THE MEAN SWV OF THE HEMANGIOMAS WAS
      SIGNIFICANTLY LOWER THAN THE MALIGNANT HEPATIC TUMOR GROUPS: hemangiomas, 1.80 +/
      0.57 m/sec; HCCs, 2.66 +/- 0.94 m/sec; CCCs, 3.27 +/- 0.64 m/sec; colon cancer
      metastases, 3.70 +/- 0.61 m/sec; and other metastases, 2.82 +/- 0.96 m/sec (p <
      0.05). The area under the receiver operating characteristics curve of SWV for
      differentiating hemangiomas from malignant tumors was 0.86, with a sensitivity of
      96.4% and a specificity of 65.8% at a cut-off value of 2.73 m/sec (p < 0.05). In
      the ARFI 2D images, the malignant tumors except HCCs were stiffer and more
      conspicuous as compared with the hemangiomas (p < 0.05). CONCLUSION: ARFI
      elastography with ARFI quantification and ARFI 2D imaging may be useful for
      differentiating hepatic hemangiomas from malignant hepatic tumors.

PMID- 24043968
TI  - Pretreatment evaluation with contrast-enhanced ultrasonography for percutaneous
      radiofrequency ablation of hepatocellular carcinomas with poor conspicuity on
      conventional ultrasonography.
AB  - OBJECTIVE: To determine whether pretreatment evaluation with contrast-enhanced
      ultrasonography (CEUS) is effective for percutaneous radiofrequency ablation
      (RFA) of hepatocellular carcinoma (HCC) with poor conspicuity on conventional
      ultrasonography (US). MATERIALS AND METHODS: This retrospective study was
      approved by the institutional review board and informed consent was waived. From
      June 2008 to July 2011, 82 patients having HCCs (1.2 +/- 0.4 cm) with poor
      conspicuity on planning US for RFA were evaluated with CEUS prior to percutaneous
      RFA. We analyzed our database, radiologic reports, and US images in order to
      determine whether the location of HCC candidates on planning US coincide with
      that on CEUS. To avoid incomplete ablation, percutaneous RFA was performed only
      when HCC nodules were identified on CEUS. The rate of technical success was
      assessed. The cumulative rate of local tumor progression was estimated with the
      use of the Kaplan-Meier method (mean follow-up: 24.0 +/- 13.0 months). RESULTS:
      Among 82 patients, 73 (89%) HCCs were identified on CEUS, whereas 9 (11%) were
      not. Of 73 identifiable HCCs on CEUS, the location of HCC on planning US
      corresponded with that on CEUS in 64 (87.7%), whereas the location did not
      correspond in 9 (12.3%) HCCs. Technical success was achieved for all 73
      identifiable HCCs on CEUS in a single (n = 72) or two (n = 1) RFA sessions.
      Cumulative rates of local tumor progression were estimated as 1.9% and 15.4% at 1
      and 3 years, respectively. CONCLUSION: Pretreatment evaluation with CEUS is
      effective for percutaneous RFA of HCCs with poor conspicuity on conventional US.

PMID- 24043969
TI  - Primary malt lymphoma of the common bile duct.
AB  - Primary mucosa-associated lymphoid tissue (MALT) lymphoma arising in the common
      bile duct (CBD) is extremely rare. In our case of MALT lymphoma, CT and MRI
      showed long, segmental, irregular wall thickening of the CBD and minimal
      dilatation of the upstream bile duct. A preoperative diagnosis of
      cholangiocarcinoma was made, but histologic evaluation confirmed MALT lymphoma of
      the CBD. We herein present a rare case of MALT lymphoma of the CBD with CT and
      MRI findings. 

PMID- 24043970
TI  - Diffusion-weighted MRI in intrahepatic bile duct adenoma arising from the
      cirrhotic liver.
AB  - A 64-year-old male patient with liver cirrhosis underwent a CT study for
      hepatocellular carcinoma surveillance, which demonstrated a 1.4-cm hypervascular
      subcapsular tumor in the liver. On gadoxetic acid-enhanced MRI, the tumor showed
      brisk arterial enhancement and persistent hyperenhancement in the portal phase,
      but hypointensity in the hepatobiliary phase. On diffusion-weighted MRI, the
      tumor showed an apparent diffusion coefficient twofold greater than that of the
      background liver parenchyma, which suggested that the lesion was benign. The
      histologic diagnosis was intrahepatic bile duct adenoma with alcoholic liver
      cirrhosis. 

PMID- 24043971
TI  - An immunoglobulin G4-related sclerosing disease of the small bowel: CT and small
      bowel series findings.
AB  - Immunoglobulin G4 (IgG4)-related sclerosing disease is rare and is known to
      involve various organs. We present a case of histologically proven IgG4-related
      sclerosing disease of the small bowel with imaging findings on computed
      tomography (CT) and small bowel series. CT showed irregular wall thickening, loss
      of mural stratification and aneurysmal dilatation of the distal ileum. Small
      bowel series showed aneurysmal dilatations, interloop adhesion with traction and
      abrupt angulation. 

PMID- 24043972
TI  - Unusual features in an adult pancreatic hemangioma: CT and MRI demonstration.
AB  - Hemangiomas in the pancreas are very rare and only a few cases in adulthood have
      been reported in the literature. We describe a case of pancreatic hemangiomas in
      an adult with unique imaging findings. A 23-year-old woman visited the hospital
      for an incidentally detected pancreatic mass. CT and MRI revealed a multilocular
      cyst with fluid-fluid levels and no obvious enhancement. The patient underwent
      surgery and the mass was confirmed as a pancreatic hemangioma. The radiological
      features and differential diagnosis of this rare lesion are discussed. 

PMID- 24043973
TI  - MDCT findings of right circumaortic renal vein with ectopic kidney.
AB  - Anomalies of renal vasculature combined with ectopic kidneys were found on a
      multi-detector CT scan. Knowledge of renal vascular variation is very important
      for surgical exploration, radiologic intervention and staging for urologic
      cancer. We present an extremely rare case of a right circumaortic renal vein
      combined with a right ectopic kidney. The right kidney was located at the level
      between the third and fifth lumbar vertebra. The right circumaortic renal vein
      crossed the aorta and returned to the inferior vena cava behind the aorta. 

PMID- 24043974
TI  - Percutaneous placement of self-expandable metallic stents in patients with
      obstructive jaundice secondary to metastatic gastric cancer after gastrectomy.
AB  - OBJECTIVE: To evaluate the outcomes of patients undergoing percutaneous
      placements of a biliary stent for obstructive jaundice secondary to metastatic
      gastric cancer after gastrectomy. MATERIALS AND METHODS: Fifty patients (mean
      age, 62.4 years; range, 27-86 years) who underwent percutaneous placements of a
      biliary stent for obstructive jaundice secondary to metastatic gastric cancer
      after gastrectomy were included. The technical success rate, clinical success
      rate, complication rate, stent patency, patient survival and factors associated
      with stent patency were being evaluated. RESULTS: The median interval between the
      gastrectomy and stent placement was 23.1 months (range, 3.9-94.6 months). The 50
      patients received a total of 65 stents without any major procedure-related
      complications. Technical success was achieved in all patients. The mean total
      serum bilirubin level, which had been 7.19 mg/dL +/- 6.8 before stent insertion,
      decreased to 4.58 mg/dL +/- 5.4 during the first week of follow-up (p < 0.001).
      Clinical success was achieved in 42 patients (84%). Percutaneous transhepatic
      biliary drainage catheters were removed from 45 patients (90%). Infectious
      complications were noted in two patients (4%), and stent malfunction occurred in
      seven patients (14%). The median stent patency was 233 +/- 99 days, and the
      median patient survival was 179 +/- 83 days. Total serum bilirubin level after
      stenting was an independent factor for stent patency (p = 0.009). CONCLUSION:
      Percutaneous transhepatic placement of a biliary stent for obstructive jaundice
      secondary to metastatic gastric cancer after gastrectomy is a technically
      feasible and clinically effective palliative procedure.

PMID- 24043975
TI  - Irreversible electroporation of a hepatocellular carcinoma lesion adjacent to a
      transjugular intrahepatic portosystemic shunt stent graft.
AB  - We report in a 65-year-old man hepatocellular carcinoma adjacent to a
      transjugular intrahepatic portosystemic shunt stent-graft which was successfully
      treated with irreversible electroporation (IRE). IRE is a new non-thermal tissue
      ablation technique which uses electrical pulses to induce cell necrosis by
      irreversible membrane poration. IRE proved to be more advantageous in the
      ablation of perivascular tumor with little injury to the surrounding structures. 

PMID- 24043976
TI  - Use of amplatzer vascular plug to treat a biliary cutaneous fistula.
AB  - Several substances have been used in an attempt to sclerose biliary ducts
      associated with persistent biliary-cutaneous fistula (BCF). The AMPLATZER
      Vascular Plug (AVP; AGA Medical, USA) system is a recently developed endovascular
      occlusion device, introduced as an alternative to permanent embolic materials
      (metallic coils or acrylic glue), in the occlusion of large and medium-calibre
      arteries and veins. We report a successful use of the AVP to embolize BCF,
      developed after the removal of an internal-external biliary drainage. 

PMID- 24043977
TI  - Combination therapy of temporary tracheal stenting and radiofrequency ablation
      for multinodular thyroid goiter with airway compression.
AB  - We report a case of multinodular thyroid goiter in an 80-year-old man who
      successfully underwent tracheal stent placement for respiratory distress caused
      by the thyroid goiter and following two radiofrequency (RF) ablation sessions
      performed for thyroid volume reduction. This sequential treatment allowed
      elective stent removals four weeks after the second RF ablation session because
      the thyroid volume had been progressively reduced. Combination therapy of
      temporary airway stenting and RF ablation for the treatment of thyroid goiter has
      two advantages, i.e., immediate reliefs of dyspnea with airway stenting and
      reductions of the thyroid volume with RF ablation, and thus, allowing symptom
      reliefs even after the stent removals. 

PMID- 24043978
TI  - MRI features of spinal epidural angiolipomas.
AB  - OBJECTIVE: To describe the MRI findings in ten patients of spinal epidural
      angiolipoma for differentiated diagnosis presurgery. MATERIALS AND METHODS: Ten
      surgically proved cases of spinal epidural angiolipomas were retrospectively
      reviewed, and the lesion was classified according to the MR findings. RESULTS:
      Ten tumors were located in the superior (n = 4), middle (n = 2), or inferior (n =
      4) thoracic level. The mass, with the spindle shape, was located in the posterior
      epidural space and extended parallel to the long axis of the spine. All lesions
      contained a fat and vascular element. The vascular content, correlating with the
      presence of hypointense regions on T1-weighted imaging (T1WI) and hyperintense
      signals on T2-weighted imaging, had marked enhancement. However, there were no
      flow void signs on MR images. All tumors were divided into two types based on the
      MR features. In type 1 (n = 3), the mass was predominantly composed of lipomatous
      tissue (> 50%) and contained only a few small angiomatous regions, which had a
      trabeculated or mottled appear. In type 2 (n = 7), the mass, however, was
      predominantly composed of vascular components (> 50%), which presented as large
      foci in the center of the mass. CONCLUSION: Most spinal epidural angiolipomas
      exhibit hyperintensity on T1WI while the hypointense region on the noncontrast
      T1WI indicates to be vascular, which manifests an obvious enhancement with
      gadolinium administration.

PMID- 24043979
TI  - Desmoid type fibromatosis in the facet joint of lumbar spine: case report and
      review of literature.
AB  - Desmoid type fibromatosis is a benign fibroblastic tumor arising from the fascia
      or musculoaponeurosis. It may occur in various locations, but most commonly in
      the shoulder girdle and neck; to our knowledge, there has been no reported case
      originating from a facet joint of the spine. We report CT and MR imaging findings
      of a desmoid type fibromatosis, involving the facet joint of the L3-4 spine with
      bone involvement. 

PMID- 24043980
TI  - Image-guided percutaneous lipiodol-pingyangmycin suspension injection therapy for
      sacral chordoma.
AB  - A 74-year-old man presented with a progressively worsening pain in sacrum and was
      diagnosed to have a sacral chordoma by biopsy in May, 2004. Percutaneous
      intratumoral injection with lipiodol-pingyangmycin suspension (LPS) was carried
      out under image guidance and repeated when the pain in sacrum recurred and the
      tumor increased. During a 6-year follow-up period, three sessions of this
      treatment were executed. CT imaging and Karnofsky Performance Score were used to
      evaluate the size of tumor and quality of life, respectively. The patient was
      free of pain after each procedure and had a high quality of life with a Karnofsky
      Performance Score above 80 points. The tumor lesion in sacral area was
      effectively controlled. No complications were observed. Percutaneous intratumoral
      injection with LPS under image guidance may be an effective and safe alternative
      for the patients with sacral chordoma. 

PMID- 24043981
TI  - Arachnoid cyst in oculomotor cistern.
AB  - Oculomotor cistern is normal anatomic structure that is like an arachnoid-lined
      cerebrospinal fluid-filled sleeve, containing oculomotor nerve. We report a case
      of arachnoid cyst in oculomotor cistern, manifesting as oculomotor nerve palsy.
      The oblique sagittal MRI, parallel to the oculomotor nerve, showed well-defined
      and enlarged subarachnoid spaces along the course of oculomotor nerve. Simple
      fenestration was done with immediate regression of symptom. When a disease
      develops in oculomotor cistern, precise evaluation with proper MRI sequence
      should be performed to rule out tumorous condition and prevent injury of the
      oculomotor nerve. 

PMID- 24043982
TI  - Initial experience with the new double-lumen scepter balloon catheter for
      treatment of wide-necked aneurysms.
AB  - OBJECTIVE: A new double-lumen balloon catheter was being developed for the
      treatment of cerebral aneurysms. The purpose of this study is to report our
      initial experience of a double-lumen balloon catheter for the treatment of wide
      necked aneurysms. MATERIALS AND METHODS: Seventeen patients (mean age, 63 years;
      range, 45-80 years) with wide-necked, with or without a branch-incorporated
      aneurysms, (10 ruptured and 9 unruptured) were treated with balloon-assisted coil
      embolization using a double-lumen balloon catheter (Scepter CTM or Scepter XCTM)
      for 7 months after being introduced to our country. Locations of the aneurysms
      were posterior communicating artery (n = 7), anterior communicating artery or A2
      (n = 7), middle cerebral artery (MCA) bifurcation (n = 3), basilar artery tip (n
      = 1) and anterior choroidal artery (n = 1). The initial clinical and angiographic
      outcomes were retrospectively evaluated. RESULTS: Coil embolization was
      successfully completed in all 19 aneurysms, resulting in complete occlusions (n =
      18) or residual neck (n = 1). In one procedure, a thrombus formation was detected
      at the neck portion of the ruptured MCA bifurcation aneurysm near to the end of
      the procedure. It was completely resolved with an intra-arterial infusion of
      Glycoprotein IIb/IIIa inhibitor (Tirofiban, 1.0 mg) without any clinical sequela.
      There were no treatment-related events in the remaining 18 aneurysms. At
      discharge, functional neurological state improved in 11 patients (10 patients
      with ruptured aneurysm and 1 with unruptured aneurysm presenting with mass
      symptoms) and 6 patients with unruptured aneurysms had no newly developed
      symptoms. CONCLUSION: In this preliminary case series, the newly developed double
      lumen Scepter balloon appears to be a safe and convenient device for coil
      embolization of wide-necked aneurysms.

PMID- 24043983
TI  - An incidentally found inflamed uterine myoma causing low abdominal pain, using Tc
      99m-tektrotyd single photon emission computed tomography-CT hybrid imaging.
AB  - We report the case of a 50-year-old woman presented with a history of right
      hemicolectomy due to an ileocecal neuroendocrine tumor and left breast
      metastasis. Owing to a slightly elevated chromogranin A-level and lower abdominal
      pain, single photon emission computed tomography-computer tomography (SPECT-CT)
      was performed. There were no signs of recurrence on the SPECT-CT scan, but the
      patient was incidentally found to have an inflamed intramural myoma. We believe
      that the slightly elevated chromogranin A-level was caused by the hypertension
      that the patient presented. In the clinical context, this is a report of an
      inflamed uterine myoma seen as a false positive result detected by TC-99m-Tc
      EDDA/HYNIC-Tyr3-Octreotide (Tektrotyd) SPECT-CT hybrid imaging. 

PMID- 24043984
TI  - Multi-detector row computed tomographic evaluation of a rare type of complete
      vascular ring: double aortic arch with atretic left arch distal to the origin of
      left subclavian artery.
AB  - Double aortic arch with an atretic left arch distal to the origin of left
      subclavian artery was diagnosed with multi-detector row computed tomography
      (MDCT) in two children with dysphagia. This rare type of complete vascular ring
      is clinically important because it may be confused with right aortic arch in
      mirror imaging. Anatomic details of this rare type of complete vascular ring
      demonstrated on MDCT facilitated appropriate surgical treatment. 

PMID- 24043985
TI  - Severe posterior reversible encephalopathy in pheochromocytoma: importance of
      susceptibility-weighted MRI.
AB  - Pheochromocytoma is a rare cause of hypertension in children. Hypertension is one
      of the common reasons of posterior reversible encephalopathy. Intracerebral
      hemorrhage is a serious and unexpected complication of hypertensive
      encephalopathy due to pheochromocytoma, and very rarely seen in the childhood.
      Intracerebral hemorrhages should be searched if there are hypertensive reversible
      signal changes on the brain. Susceptibility weighted imaging (SWI) is a more
      sensitive method than conventional MRI when demonstrating cerebral
      microhemorrhagic foci. This is the first report of SWI findings on intracerebral
      hemorrhages in basal ganglia, brain stem and periventricular white matter due to
      hypertensive encephalopathy in a child with pheochromocytoma. 

PMID- 24043986
TI  - Visualization of peripheral pulmonary artery red thrombi utilizing optical
      coherence tomography.
AB  - Optical coherence tomography (OCT) is a new imaging technique capable of
      obtaining high-resolution intravascular images and has been used in
      interventional cardiology. However, an application of OCT in pulmonary arteries
      had seldom been documented. In this case, OCT imaging is performed in peripheral
      pulmonary arteries and shows mural red thrombi. Subsequently, the red thrombi are
      aspirated and confirmed by a histological examination. These findings suggest
      that OCT may be a useful tool to depict peripheral pulmonary artery thrombi. 

PMID- 24043987
TI  - Sandstorm appearance of pulmonary alveolar microlithiasis incidentally detected
      in a young, asymptomatic male.
AB  - Pulmonary alveolar microlithiasis (PAM) is a rare chronic disease with paucity of
      symptoms in contrast to the imaging findings. We present a case of a 24-year-old
      Malay man having an incidental abnormal pre-employment chest radiograph of dense
      micronodular opacities giving the classical "sandstorm" appearance. High
      resolution computed tomography of the lungs showed microcalcifications with
      subpleural cystic changes. Open lung biopsy showed calcospherites within the
      alveolar spaces. The radiological and histopathological findings were
      characteristic of PAM. 

PMID- 24043988
TI  - Re: aberrant vascular structures and its effect on the adjacent organs: how can
      we evaluate efficiently and safely?

PMID- 24043989
TI  - Re: diffusion-weighted imaging of prostate cancer: how can we use it accurately?

PMID- 24043990
TI  - Malaysian Journal of Medical Sciences Striving towards Visibility.
AB  - The Malaysian Journal of Medical Sciences has in its 25 years "Silver Jubilee"
      achieved another milestone of being visible to the biomedical community when it
      was accepted in PubMed. The journal aim to increase its readership so as to
      increase impact in the biomedical field amongst its Asian readers despite having
      a high rejection rate. This was done to maintain quality of the manuscripts
      published over the years. PubMed listing should enable more manuscripts to be
      cited as its the leading biomedical journal for the Asian community. 

PMID- 24043991
TI  - Four Possible Itching Pathways Related to the TRPV1 Channel, Histamine, PAR-2 and
      Serotonin.
AB  - The following four possible pathways for itching sensation have been suggested by
      recent reports. 1) Histaminergic TRPV1-positive pathway: Although histamine
      positive nerve fibers cannot strictly be classified as "itch specific" due to
      their excitation also by pure algogens (making them itch-selective), the
      existence of a subpopulation of nociceptors responsible for itching is strongly
      suggested. Moreover, the TRPV1-expressing neurons have been suggested to be the
      main sensors and mediators of itching. 2) Histaminergic TRPV1-negative pathway:
      The scratching behavior caused by itching was not different between capsaicin-pre
      treated and vehicle-treated (control) mast cell-rich NC mice. This result
      suggests the existence of a capsaicin-insensitive (TRPV1-negative) histaminergic
      pathway. 3) Non-histaminergic PAR-2 pathway: Protease-activated receptor 2 (PAR
      2) has been shown to play a role in the itching of atopic dermatitis (AD). The
      itch evoked by cowhage (a non-histaminergic pruritogen that activates PAR-2) is
      very similar in characteristics to the itch evoked by conditions such as AD. 4)
      Non-histaminergic serotonin (5-HT) pathway: 5-HT alone applied to the human skin
      evokes an itching sensation and has been suggested to be involved in the itching
      associated with pruritic diseases, such as polycythemia vera and cholestasis. 

PMID- 24043992
TI  - Frequencies of Cytochrome P450 2B6 and 2C8 Allelic Variants in the Mozambican
      Population.
AB  - BACKGROUND: The cytochrome P450 enzymes (CYP) play an important role in the
      metabolism of many therapeutic agents. The activities of different enzymes
      exhibit variability in different populations, which causes variations in drug
      response or toxicity. The CYP2B6 and CYP2C8 enzymes are encoded by polymorphic
      genes characterised by different single nucleotide polymorphisms (SNPs). Several
      of these CYP variants are often associated with slow metabolism phenotypes. This
      study aimed to analyse the frequencies of allelic variants of CYP2B6 and CYP2C8
      in the Mozambican population. METHODS: Using a polymerase chain reaction and
      restriction fragment length polymorphism assay (PCR-RFLP), the frequencies of the
      allelic variants of CYP2B6 (c.64C>T, c.516G>T, c.777C>A, c.785A>G, c.1459C>T) and
      CYP2C8 (c.805A>T, c.416G>A, c.1196A>G, c.792C>G) were determined in 360
      Mozambican blood donors. RESULTS: The frequencies of the allelic variants of the
      CYP2B6 gene were 0.057, 0.426, 0.0, 0.410, and 0.004. For the CYP2C8 gene, the
      frequencies of the allelic variants were 0.160, 0.048, 0.0, and 0.005. No
      significant differences were observed between the gender and geographic
      distribution of volunteers around the country. CONCLUSION: The frequencies of the
      allelic variants of the CYP2B6 and CYP2C8 genes were found to be homogeneously
      distributed in the Mozambican population and were comparable to other African
      populations. Further studies are required to explore the impact of these variants
      on the clinical response (efficacy and toxicity) of drugs, including
      antimalarials.

PMID- 24043993
TI  - MR Volumetry of Hippocampus in Normal Adult Malay of Age 50 Years Old and Above.
AB  - BACKGROUND: Hippocampal volume is affected by several psychiatric illnesses of
      old age, as well as by normal aging. It is important to have a normal data in a
      population to assist in diagnosis. The aim of this study is to determine
      hippocampal volume in normal Malay people aged 50 years old and older. METHODS:
      This was a cross-sectional study of the normal Malay population aged 50 to 77
      years. We included 43 participants, representing 19 men and 24 women. Magnetic
      resonance imaging (MRI) was performed using a GE Signa Horizon LX 1.0 Tesla.
      Oblique coronal images of temporal lobes were obtained and hippocampal volumetry
      was done manually and normalised with intracranial volume. RESULTS: Mean right
      and left hippocampal volumes (HCVs) were 3.43 cm3 (SD 0.32) and 3.26 cm3 (SD
      0.34), with a significant difference between them (P < 0.001). Total mean HCVs
      exhibited no significant difference between men and women (P = 0.234). The means
      of the normalised right and left HCVs were 3.42 cm3 (SD 0.31) and 3.26 cm3 (SD
      0.32). CONCLUSION: The mean right and left hippocampal volumes were significantly
      different in this study. Men had slightly larger mean HCVs but the difference was
      not statistically significant. It was found that normalisation further reduces
      the mean volume difference between the genders.

PMID- 24043994
TI  - Electrodiagnostic evaluation of peripheral nervous system changes in patients
      with multiple sclerosis.
AB  - BACKGROUND: There is supportive evidence that multiple sclerosis (MS) could
      potentially affect the peripheral nervous system. We assessed peripheral sensory
      and motor nerve involvement in patients with MS by a nerve conduction velocity
      test. METHODS: We studied 75 patients who had a relapsing-remitting or secondary
      progressive pattern. We measured amplitude, latency, conduction velocity,
      Hoffmann reflex (H-Reflex), and F-Waves. RESULTS: The amplitude of the right
      tibial, right proneal, left tibial, left proneal, and left median motor nerves
      was less than the mean for the normal population. Right ulnar sensory conduction
      in the patients showed an amplitude that was less than that of the normal
      population; there was no significant change in the amplitude of other sensory
      nerves. Latencies of the right and left median and right proneal motor nerves and
      left ulnar sensory nerves were statistically less than that of the normal
      population. Mean motor conduction velocity and F-wave conduction did not differ
      significantly from the normal population. H-reflex latencies of the right and
      left lower limbs were significantly more prolonged than those of the normal
      population. CONCLUSION: Our results suggest possible peripheral motor nerve
      abnormalities in MS patients, especially with the amplitude of the motor nerves;
      however, our results do not demonstrate any significant difference among the
      nerve conduction velocity parameters of sensory nerves between MS patients and
      the normal population.

PMID- 24043995
TI  - Prevalence of oral mucosal lesions in patients with type 2 diabetes attending
      hospital universiti sains malaysia.
AB  - OBJECTIVES: Diabetes mellitus is associated with a greater likelihood of
      developing certain oral mucosal disorders. This study was aimed at assessing the
      prevalence of oral mucosal lesions (OMLs) in patients with type 2 diabetes (DM2)
      and to investigate the association of such lesions with metabolic control of the
      disease. METHODS: This cross-sectional study involved 391 patients with DM2 and
      391 non-diabetic control subjects. Demographic information and data on the
      duration and type of diabetes, glycosylated hemoglobin (HbA1c) values, medical
      history, and current use of medication were obtained from medical records.
      Detailed oral examination was performed in accordance with international
      criteria. RESULTS: The prevalence of OMLs was significantly higher among diabetic
      patients (45.5%) than among control subjects (38.4%) (P = 0.042). Patients with
      diabetes had a higher prevalence of geographic tongue (GT) (P = 0.017), denture
      stomatitis (P = 0.018), and angular cheilitis (P = 0.006) than controls. Overall,
      diabetic patients with poor metabolic control had a significantly higher
      prevalence of OMLs and xerostomia than patients with moderately and well
      controlled disease (P < 0.05). CONCLUSION: The prevalence of OMLs was
      significantly higher in diabetic patients than in control subjects. Higher
      occurrence of OMLs was significantly associated with poor metabolic control.

PMID- 24043996
TI  - Drug utilization review of potassium chloride injection formulations available in
      a private hospital in kuching, sarawak, malaysia.
AB  - BACKGROUND: The concentrated potassium chloride injection is a high-alert
      medication and replacing it with a pre-mixed formulation can reduce the risks
      associated with its use. The aim of this study was to determine the clinical
      characteristics of patients receiving different potassium chloride formulations
      available at a private institution. The study also assessed the effectiveness and
      safety of pre-mixed formulations in the correction of hypokalaemia. METHODS: This
      was a retrospective observational study consisting of 296 cases using
      concentrated and pre-mixed potassium chloride injections in 2011 in a private
      hospital in Kuching, Sarawak, Malaysia. RESULTS: There were 135 (45.6%) cases
      that received concentrated potassium chloride, and 161 (54.4%) cases that
      received pre-mixed formulations. The patients' clinical characteristics that were
      significantly related to the utilization of the different formulations were
      diagnosis (P < 0.001), potassium serum blood concentration (P < 0.05), and fluid
      overload risk (P < 0.05). The difference observed for the cases that achieved or
      maintained normokalaemia was statistically insignificant (P = 0.172). Infusion
      related adverse effects were seen more in pre-mixes compared to concentrated
      formulations (6.8% versus 2.2%, P < 0.05). CONCLUSION: This study provides
      insight into the utilization of potassium chloride injections at this specific
      institution. The results support current recommendations to use pre-mixed
      formulations whenever possible.

PMID- 24043997
TI  - Nursing Students' Perceptions of their Educational Environment Based on DREEM
      Model in an Iranian University.
AB  - BACKGROUND: The learning climate has been found to be significant in determining
      students' academic achievement and learning. The purpose of this study was to
      measure the viewpoints of nursing students toward their learning environment at
      Rafsanjan University of Medical Sciences (RUMS). METHODS: This descriptive, cross
      sectional study was performed on 202 nursing students using the Dundee Ready
      Educational Environment Measure (DREEM). The items, as well as scale scores were
      compared among nursing students. Also, data was analysed by SPSS19 using t test
      and ANOVA. RESULTS: The total mean DREEM score was 114.3 (SD 20.6) out of 200
      (corresponding to 57.15% of the maximum score), which was considered as more
      positive than negative. The subscale with the highest mean score was Students'
      Perceptions of learning. Mean score of this subscale was 27.3/48 0 (SD 5.9)
      corresponding to 56.87% of the maximum score. The lowest mean score was for the
      Academic Self-perceptions 20.31/32 (SD 4.51) (53.44%), The total DREEM score for
      female students was significantly higher than for males (P = 0.01). The total
      scores of new entry students were significantly higher than the others (P =
      0.01). CONCLUSION: The school's educational climate was generally perceived
      positively by students, but specific areas identified by students as needing
      improvement. It is essential for managers to make a greater effort to create an
      appropriate educational environment in order to provide and maintain high quality
      learning environments for students.

PMID- 24043998
TI  - The Predicaments of People Whose Suicide was Captured on Film.
AB  - BACKGROUND: Although suicide is commonly linked with mental disorder, the notion
      that suicide may occur in response to predicaments has been the subject of much
      recent study and attention. A predicament in this context refers to an
      uncomfortable situation from which escape is difficult. We aimed to examine the
      predicaments of people whose suicide was captured on film and displayed on the
      public record. METHODS: The authors' extensive private library and the web were
      explored for examples of suicide on film. The authors viewed the films and
      associated records, and extracted and listed details of the suicides. RESULTS:
      Six individual cases and two groups (totalling 2200 plus individuals) were
      identified. The individual cases were Thich Quang Duc (1963), Christine Chubbuck
      (1974), Budd Dwyer (1987), Daniel Victor Jones (1998), Michael Marin (2012) and
      Jordon Romero (2012). The two groups were the Japanese Kamikaze pilots of
      1944/1995, and those who jumped from the burning "Twin Towers" on September 11,
      2001. One of the six individuals has evidence of a mental disorder, and all
      (individual and group cases) were in potent social/environmental predicaments.
      CONCLUSION: Both psychological autopsies and our clinical experience suggest that
      suicide is often associated with mental disorder. Nevertheless,
      social/environmental predicaments may lead to suicide. This study suggests that
      individuals whose suicide is captured on film are often seeking public exposure
      of their fatal act.

PMID- 24043999
TI  - Trends in the antibiotic resistance patterns of enteric Fever isolates - a three
      year report from a tertiary care centre.
AB  - BACKGROUND: The incidence of multidrug resistant enteric fever is increasing
      alarmingly. This study was planned to determine the rate of isolation of
      Salmonella spp. and to compare the isolates for their epidemiological parameters
      and antimicrobial susceptibility patterns at our center. METHODS: The study was
      conducted over a span of three years with a total of 8142, 8134, and 8114 blood
      culture samples processed for the years 2008, 2009, and 2010 respectively. The
      minimum inhibitory concentration (MIC) for ciprofloxacin and chloramphenicol was
      determined using an agar dilution method. The MIC for ciprofloxacin was also
      confirmed by Epsilon-test (E -test) strips. RESULTS: Of the total 302 Salmonella
      spp. isolated, 257 were Salmonella enterica serotype Typhi (85.1%) and 45 (14.9%)
      were S. enterica serotype Paratyphi A. The majority of the isolates recovered
      were from the pediatric age group (54.6%) and males (60.6%). Complete
      susceptibility was observed to chloramphenicol, cefotaxime, ceftriaxone, and
      azithromycin over the last two years (2009 and 2010), with an increase in
      resistance to nalidixic acid (100%) and ciprofloxacin (13.6%). CONCLUSION: In our
      study, we found augmentation of resistance to nalidixic acid and fluoroquinolones
      and complete sensitivity to ceftriaxone along with reemergence of chloramphenicol
      sensitivity for Salmonella isolates. This report emphasises the necessity of
      continuous surveillance of antibiograms of enteric fever isolates in an area.

PMID- 24044000
TI  - Clinical comparison of one recovered case and one fatal case of human infection
      with H7N9 avian influenza in Shanghai Public Health Clinical Center in China.
AB  - H7N9 avian influenza is the latest subtype of influenza virus to emerge in the
      world. By April 17, 2013 in Shanghai, a total of 31 confirmed cases were
      reported, and 11 of these patients died. The epidemiological characteristics and
      the clinical progress of this new human flu infection are still not clear.
      Thirteen confirmed patients have now been treated in Shanghai Public Health
      Clinical Center. Among the first batch of patients, hospitalised at the beginning
      of April 2013, two who were admitted with the same estimated date of onset of
      disease had very different outcomes. After active treatment at the Centre, one
      recovered by April 18, 2013, but one patient entered critical condition and died
      on April 11, 2013. The clinical and laboratory characteristics in hospital are
      here analysed and compared to learn more about H7N9 avian influenza. Confirmation
      that the observed differences are valuable for prognosis and treatment decisions
      for H7N9 patients awaits authentication by analysis of more patients. 

PMID- 24044001
TI  - Human adipose tissue derived stem cells as a source of smooth muscle cells in the
      regeneration of muscular layer of urinary bladder wall.
AB  - BACKGROUND: Adipose tissue provides an abundant source of multipotent cells,
      which represent a source of cell-based regeneration strategies for urinary
      bladder smooth muscle repair. Our objective was to confirm that adipose-derived
      stem cells (ADSCs) can be differentiated into smooth muscle cells. METHODS: In
      this study, adipose tissue samples were digested with 0.075% collagenase, and the
      resulting ADSCs were cultured and expanded in vitro. ADSCs at passage two were
      differentiated by incubation in smooth muscle inductive media (SMIM) consisting
      of MCDB I31 medium, 1% FBS, and 100 U/mL heparin for three and six weeks. ADSCs
      in non-inductive media were used as controls. Characterisation was performed by
      cell morphology and gene and protein expression. RESULT: The differentiated cells
      became elongated and spindle shaped, and towards the end of six weeks, sporadic
      cell aggregation appeared that is typical of smooth muscle cell culture. Smooth
      muscle markers (i.e. alpha smooth muscle actin (ASMA), calponin, and myosin heavy
      chain (MHC)) were used to study gene expression. Expression of these genes was
      detected by PCR after three and six weeks of differentiation. At the protein
      expression level, ASMA, MHC, and smoothelin were expressed after six weeks of
      differentiation. However, only ASMA and smoothelin were expressed after three
      weeks of differentiation. CONCLUSION: Adipose tissue provides a possible source
      of smooth muscle precursor cells that possess the potential capability of smooth
      muscle differentiation. This represents a promising alternative for urinary
      bladder smooth muscle repair.

PMID- 24044002
TI  - Imprint cytological diagnosis of colonic adenocarcinoma metastatic to liver.
AB  - The liver is a common visceral site for metastatic tumours. Radiological features
      of the liver, fine needle aspiration cytology (FNAC) and histopathological
      evaluation (HPE) of liver nodules have a significant role in pre-operative
      diagnosis of liver lesions. In an intraoperative setting, frozen section biopsy
      plays a major diagnostic modality but the role of imprint cytology of liver
      nodules is also appealing. Imprint cytology is a valuable and precise tool in
      diagnosing the lesions for a rapid intraoperative diagnosis. This study presents
      a case of colorectal cancer liver metastasis diagnosed by imprint cytology
      intraoperatively. 

PMID- 24044003
TI  - Chordoid meningioma, part of a multiple intracranial meningioma: a case report &
      review.
AB  - Chordoid meningioma, classified as atypical meningioma according to the World
      Health Organisation (WHO) classification, is a rare subtype, which represents
      only 0.5% of all meningiomas and is associated with a high incidence of
      recurrence. Multiple intracranial meningiomas are rare in non-neurofibromatosis
      patients. We present a female patient with both of these rare types of
      meningioma. The patient presented with two concurrent intracranial meningiomas,
      with one a meningotheliomatous subtype and the other a chordoid meningioma. Given
      the wide array of histological differential diagnoses in chordoid meningioma,
      immunohistochemistry has a significant role to play in differentiating them.
      Recurrence in chordoid meningioma can be generally predicted based on the extent
      of resection, the percentage of chordoid element, and proliferation indices. 

PMID- 24044004
TI  - Management and prevention of recurrent paratesticular liposarcoma.
AB  - Paratesticular liposarcoma is a rare entity. Compared to other genitourinary
      sarcoma, it is usually detected earlier and is easily resectable, resulting in an
      excellent prognosis. The recurrence of well-differentiated paratesticular
      liposarcoma after complete resection is extremely rare. Optimal management of the
      tumour recurrence includes complete re-excision and radiotherapy to the area of
      recurrence. Here, we describe a 48-year-old man with a recurrent left
      paratesticular well-differentiated liposarcoma, six years after its complete
      excision. Our discussion focused on the therapeutic strategy to prevent tumour
      recurrence. It is hoped that this case discussion can increase the awareness of
      this condition and assist in its management. 

PMID- 24044005
TI  - Right phrenic nerve palsy: a rare presentation of thoracic aortic aneurysm.
AB  - Phrenic nerve palsy causing hemidiaphragm paralysis is a very uncommon feature of
      thoracic aortic aneurysm. In one case, a 45-year-old man complained of chronic
      chest pain, dysphagia, and hoarseness of voice; posteroanterior view chest
      radiograph revealed lobular enlargement of the superior mediastinum and elevated
      right hemidiaphragm. Contrast-enhanced computed tomography (CT) of the thorax
      revealed a giant partially thrombosed aneurysm originating from the ascending
      aorta and extending into the aortic arch, causing a widening of the aorta
      pulmonary window and a compression of the thoracic esophagus. Right hemidiaphragm
      elevation was explained by the gross mass effect of the aneurysm on the right
      hilum, causing right phrenic nerve palsy. The patient was to be operated on for
      surgical correction of the aneurysm, but died before surgery due to spontaneous
      rupture. 

PMID- 24044006
TI  - Intraoperative Cerebrospinal Fluid Sample from First Ventriculoperitoneal Shunt
      Operation: Is it Indicated?

PMID- 24044007
TI  - Determinants of Change in Maternal Sensitivity: Contributions of Context,
      Temperament, and Developmental Risk.
AB  - OBJECTIVE: Maternal sensitivity is a fundamental parenting construct and a
      determinant of positive child outcomes and healthy parent-child relationships.
      Few longitudinal studies have investigated determinants of sensitive parenting,
      particularly in a population of children at risk for developmental delay. DESIGN:
      This study modeled trajectories of maternal sensitivity observed in two
      independent parenting contexts at child ages 3-, 4-, and 5-years. The sample
      included N = 247 mother-child dyads, with n = 110 children classified as at risk
      for developmental delays. Predictors included maternal distress, child anger
      proneness, and developmental risk status. RESULTS: Maternal sensitivity changed
      during more demanding parenting tasks over the 3-year period but not during a low
      demand task. Mothers of children with developmental risk, relative to mothers of
      typically developing children, and mothers of boys relative to mothers of girls,
      showed less sensitivity during more demanding parenting tasks. CONCLUSIONS: Early
      developmental risk and child gender contribute to the nature of maternal
      sensitivity over time, but their contributions depend on the situational demands
      of the interaction. This contextualized view of sensitivity provides further
      evidence in support of parenting as a dynamic developmental process.

PMID- 24044008
TI  - Gay bathhouse HIV prevention: the use of staff monitoring of patron sexual
      behavior.
AB  - Many HIV prevention interventions have been launched in gay bathhouses and sex
      clubs since the onset of the AIDS epidemic, such as condom distribution and HIV
      testing. Perhaps none of these are as intrusive to the venue's environment as
      what is called "monitoring," which involves staff, during every shift, repeatedly
      walking throughout the public areas of a bathhouse to check on patrons' sexual
      behavior. Yet, monitoring has received little evaluation. Between 2002 and 2004,
      we conducted qualitative interviews with venue managers, staff and patrons in New
      York City, Los Angeles, and the San Francisco Bay Area. An analysis found that
      monitoring was influenced by the kinds of space available for sex, suggesting
      three approaches to monitoring: 1) monitoring all sex in clubs that only had
      public areas where men had sex ; 2) monitoring some sex in clubs with private
      rooms for sex; and 3) no monitoring of sex, regardless of the kinds of space for
      sex. This paper explores each approach as described by club managers, staff, and
      patrons to understand the potential effectiveness of monitoring as an HIV
      prevention intervention.

PMID- 24044009
TI  - The role of large animal studies in cardiac regenerative therapy concise review
      of translational stem cell research.
AB  - Animal models have long been developed for cardiovascular research. These animal
      models have been helpful in understanding disease, discovering potential
      therapeutics, and predicting efficacy. Despite many efforts, however,
      translational study has been underestimated. Recently, investigations have
      identified stem cell treatment as a potentially promising cell therapy for
      regenerative medicine, largely because of the stem cell's ability to
      differentiate into many functional cell types. Stem cells promise a new era of
      cell-based therapy for salvaging the heart. However, stem cells have the
      potential risk of tumor formation. These properties of stem cells are considered
      a major concern over the efficacy of cell therapy. The translational/preclinical
      study of stem cells is essential but only at the beginning stages. What types of
      heart disease are indicated for stem cell therapy, what type of stem cell, what
      type of animal model, how do we deliver stem cells, and how do we improve heart
      function? These may be the key issues that the settlement of which would
      facilitate the transition of stem cell research from bench to bedside. In this
      review article, we discuss state-of-the-art technology in stem cell therapies for
      cardiovascular diseases. 

PMID- 24044010
TI  - One-Year Clinical Outcomes among Patients with Metabolic Syndrome and Acute
      Myocardial Infarction.
AB  - BACKGROUND AND OBJECTIVES: Metabolic syndrome (MetS) is an important risk factor
      for cardiovascular disease. However, the clinical outcome of acute myocardial
      infarction (AMI) with MetS has not been well examined. The purpose of this study
      was to evaluate the clinical outcomes of AMI patients with MetS. SUBJECTS AND
      METHODS: We evaluated a total of 6352 AMI patients who had successful
      percutaneous coronary interventions and could be identified for MetS between 2005
      and 2008 at 51 hospitals participating in the Korea Acute Myocardial Infarction
      Registry. They were divided into 2 groups according to the presence of MetS: the
      MetS group (n=2493, 39.2%) versus the Non-MetS group (n=3859, 60.8%). In
      addition, 4049 AMI patients with high levels of low density lipoprotein
      cholesterol (LDL-C) (>=100 mg/dL) among them, were divided into the MetS group
      (n=1561, 38.6%) versus the Non-MetS group (n=2488, 61.4%). RESULTS: In the
      overall population, there was no significant difference in 12-month the major
      adverse cardiac events (MACE) rate between the 2 groups. However, the MetS group
      showed a significantly higher 12-month MACE rate in the high LDL-C population.
      Multivariate analysis showed that MetS was an independent prognostic factor for
      12-month MACE {hazard ratio (HR) 1.607, 95% confidence interval (CI) 1.027 to
      2.513, adjusted p=0.038} and for 12-month target vessel revascularization (HR
      1.564, 95% CI 1.092 to 2.240, adjusted p=0.015) in the high LDL-C population.
      CONCLUSION: MetS patients with AMI in the overall population showed no
      significant difference in 12-month clinical outcomes. However, in patients with
      higher LDL-C >=100 mg/dL, they showed significantly worse clinical outcome than
      Non-MetS patients. Therefore, it is important to ascertain the presence of MetS
      in AMI patients, and more aggressive therapy should be strongly considered for
      AMI patient with MetS.

PMID- 24044011
TI  - Predictors of recovery of left ventricular systolic dysfunction after acute
      myocardial infarction: from the korean acute myocardial infarction registry and
      korean myocardial infarction registry.
AB  - BACKGROUND AND OBJECTIVES: We investigated the predictors of the recovery of
      depressed left ventricular ejection fraction (LVEF) in patients with moderate or
      severe left ventricular (LV) systolic dysfunction after acute myocardial
      infarction (MI). SUBJECTS AND METHODS: We analyzed 1307 patients, who had
      moderately or severely depressed LVEF (<45%) on echocardiography soon after acute
      MI and who underwent a follow-up echocardiography, among 27369 patients from the
      Korea Working Group on the Myocardial Infarction Registry. Patients were
      categorized into two groups according to recovery of LVEF: group I with
      consistently depressed LVEF (<45%) at the follow-up echocardiography and group II
      with a recovery of LVEF (>=45%). RESULTS: Recovery of LV systolic dysfunction was
      observed in 51% of the subjects (group II, n=663; DeltaLVEF, 16.2+/-9.3%),
      whereas there was no recovery in the remaining subjects (group I, n=644;
      DeltaLVEF, 0.6+/-7.1%). In the multivariate analysis, independent predictors of
      recovery of depressed LVEF were as follows {odds ratio (OR) [95% confidence
      interval (CI)]}: moderate systolic dysfunction {LVEF >=30% and <45%; 1.73 (1.12
      2.67)}, Killip class I-II {1.52 (1.06-2.18)}, no need for diuretics {1.59 (1.19
      2.12)}, non-ST-segment elevation MI {1.55 (1.12-2.16)}, lower peak troponin I
      level {<24 ng/mL, median value; 1.55 (1.16-2.07)}, single-vessel disease {1.53
      (1.13-2.06)}, and non-left anterior descending (LAD) culprit lesion {1.50 (1.09
      2.06)}. In addition, the use of statin was independently associated with a
      recovery of LV systolic dysfunction {OR (95% CI), 1.46 (1.07-2.00)}. CONCLUSION:
      Future contractile recovery of LV systolic dysfunction following acute MI was
      significantly related with less severe heart failure at the time of presentation,
      a smaller extent of myonecrosis, or non-LAD culprit lesions rather than LAD
      lesions.

PMID- 24044012
TI  - The Relationship between Microcirculatory Resistance and Fractional Flow Reserve
      in Patients with Acute Myocardial Infarction.
AB  - BACKGROUND AND OBJECTIVES: It was demonstrated that the fractional flow reserve
      (FFR) with partial balloon obstruction may have implications for assessing viable
      myocardium. In a different way, the index of microcirculatory resistance (IMR)
      was introduced as a useful indicator for assessing microvascular function. We
      evaluated the relationship between the FFR0.8 and the IMR. SUBJECTS AND METHODS:
      We studied 48 consecutive patients who had undergone coronary intervention for
      acute myocardial infarction (AMI). After revascularization using stent(s), an
      undersized short balloon was positioned inside the stent and inflated to create a
      specific normalized pressure drop of FFR (distal coronary/aortic pressure=0.80)
      at rest. The FFR0.8 was obtained during hyperemia with the fixed state balloon
      induced partial obstruction. IMR was measured by three injections of saline. The
      association between the FFR0.8 and the IMR was investigated. RESULTS: The mean
      age of the patients was 60+/-12 years and 36 (75%) overall presented with ST
      segment elevation myocardial infarction. The mean FFR0.8 was 0.68+/-0.06. A
      statistically significant correlation between the FFR0.8 and the log-transformed
      IMRtrue (LnIMRtrue) was found through a multivariable linear regression analysis
      (beta=0.056, p<0.001). Both the FFR0.8 and the LnIMRtrue had a positive
      correlation with the log-transformed peak troponin I (TnI) with statistical
      significance (r(2)=0.119, p=0.017; r(2)=0.225, p=0.006, respectively).
      CONCLUSION: There was a positive correlation between the LnIMRtrue and the
      FFR0.8. Both of the values were associated with peak TnI. Those values may be
      used as appropriate surrogate measures of microvascular function after AMI.

PMID- 24044013
TI  - Genotype- and Phenotype-Directed Personalization of Antiplatelet Treatment in
      Patients with Non-ST Elevation Acute Coronary Syndromes Undergoing Coronary
      Stenting.
AB  - BACKGROUND AND OBJECTIVES: We evaluated the effectiveness of genotype- and
      phenotype-directed individualization of P2Y12 inhibitors to decrease high on
      treatment platelet reactivity (HOPR). SUBJECTS AND METHODS: Sixty-five patients
      undergoing percutaneous coronary intervention for non-ST elevation acute coronary
      syndromes were randomly assigned to genotype- or phenotype-directed treatment.
      All patients were screened for CYP2C19(*)2, (*)3, or (*)17 alleles by using the
      Verigene CLO assay (Nanosphere, Northbrook, IL, USA). The P2Y12 reaction unit
      (PRU) was measured using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA,
      USA). 21 CYP2C19 (*)2 or (*)3 carriers (65.6%) and 11 patients with HOPR (33.3%),
      defined as a PRU value >=230, were given 90 mg ticagrelor twice daily; non
      carriers and patients without HOPR were given 75 mg clopidogrel daily. The
      primary endpoint was the percentage of patients with HOPR after 30 days of
      treatment. RESULTS: PRU decreased following both genotype- and phenotype-directed
      therapies (242+/-83 vs. 109+/-90, p<0.001 in the genotype-directed group; 216+/
      74 vs. 109+/-90, p=0.001 in the phenotype-directed group). Five subjects (16.2%)
      in the genotype-directed group and one (3.3%) in the phenotype-directed group had
      HOPR at day 30 (p=0.086). All patients with HOPR at the baseline who received
      ticagrelor had a PRU value of <230 after 30 days of treatment. Conversely,
      clopidogrel did not lower the number of patients with HOPR at the baseline.
      CONCLUSION: Tailored antiplatelet therapy according to point-of-care genetic and
      phenotypic testing may be effective in decreasing HOPR after 30 days.

PMID- 24044014
TI  - Coexistence of internal carotid artery stenosis in patients with abdominal aortic
      aneurysm.
AB  - BACKGROUND AND OBJECTIVES: Abdominal Aortic Aneurysm (AAA) and carotid disease
      have medical and social significance, considering their morbidity, disability,
      and economic consequences. The study objectives were to determine the prevalence
      of asymptomatic internal carotid artery (ICA) lesions >=70% in patients with AAA,
      the correlation of AAA diameter with the degree of ICA stenosis and symptoms, and
      the importance of preventive ultrasound checkups. SUBJECTS AND METHODS: A
      prospective non-randomized controlled study including 740 patients, aged from 18
      85 years, who were suitable for the inclusion and exclusion criteria and reported
      at the vascular laboratory of the Institute for Vascular and Endovascular
      Surgery, Clinical Center of Serbia from 1st of December 2011 to the 1st of
      November 2012. RESULTS: The prevalence of asymptomatic ICA stenosis >=70% in
      patients with AAA is 10.8%. Male representatives have more symptomatic ICA
      stenosis >=70%. Patients with small aneurysms more often have asymptomatic ICA
      stenosis >=70%. The occurrence of symptoms of carotid disease was more prevalent
      among patients with ICA stenosis >=70% compared to the group with stenosis <70%.
      There was no correlation found between the grade of ICA stenosis with the size of
      AAA. CONCLUSION: The prevalence of asymptomatic ICA stenosis >=70% in patients
      with AAA is found to be 10.8%. Male patients with ICA stenosis >=70% more often
      had symptoms of carotid disease. In the smaller aneurysms, ICA stenosis >=70%
      occurs frequently, but without the symptoms of carotid disease, and there was no
      correlation between the size of AAA and the grade of ICA stenosis. Clinical
      implications of ICA imaging in patients with previously diagnosed AAA is
      necessary.

PMID- 24044015
TI  - Acute Profound Thrombocytopenia after Using Abciximab for No-Reflow during
      Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial
      Infarction.
AB  - Glycoprotein IIb/IIIa antagonists are well established for their effectiveness in
      improving clinical outcomes in acute coronary syndrome patients undergoing
      percutaneous coronary intervention. Acute profound thrombocytopenia is a rare
      complication of abciximab. We present a case which was managed successfully for
      the rare complication of acute profound thrombocytopenia after using abciximab
      and an intra-aortic balloon pump for the treatment of a no-reflow phenomenon and
      consecutive cardiogenic shock during primary percutaneous coronary intervention. 

PMID- 24044016
TI  - Kounis syndrome presenting as very late stent thrombosis in an everolimus-eluting
      stent following wasp stings.
AB  - Kounis syndrome is the concurrence of acute coronary syndromes with conditions
      associated with mast cell activation following an allergic insult. We report a 56
      year-old man who experienced a ST-segment elevation myocardial infarction after
      wasp stings. The patient presented without signs of anaphylaxis or shock.
      Coronary angiography showed an everolimus-eluting stent thrombosis (ST) of the
      left anterior descending artery occluding the vessel completely which was
      deployed for stable angina 3 years ago. The patient had been compliant with anti
      platelet therapy, and no relevant cardiovascular events occurred until the day of
      admission. We interpreted our patient's condition as a manifestation of Kounis
      syndrome. To our knowledge, this is the first case of Kounis syndrome showing
      very late ST in a second-generation drug-eluting stent caused by wasp stings. 

PMID- 24044017
TI  - A case of reversible very low voltage electrocardiogram in fulminant myocarditis.
AB  - Clinical features of acute myocarditis range from a subclinical state to a
      fulminant state. Fulminant myocarditis with ventricular arrhythmia or
      atrioventricular block is associated with a high mortality rate. In cases in
      which aggressive medical therapy for fulminant myocarditis is not likely to be
      successful, intensive and emergency mechanical circulatory support, such as
      extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pump, should
      be considered. We report life salvage of acute fulminant myocarditis in a 53-year
      old woman presented with malignant arrhythmia and cardiogenic shock supported by
      ECMO. 

PMID- 24044018
TI  - A case of cardiac beriberi: a forgotten but memorable disease.
AB  - Thiamine (vitamin B1) serves as an important cofactor in body metabolism and
      energy production. It is related with the biosynthesis of neurotransmitters and
      the production of substances used in defense against oxidant stress. Thus, a lack
      of thiamine affects several organ systems, in particular the cardiovascular and
      nervous system. The cardiac insufficiency caused by thiamine deficiency is known
      as cardiac beriberi, with this condition resulting from unbalanced nutrition and
      chronic excessive alcohol intake. Given that the disease is now very rare in
      developed nations such as Korea, it is frequently missed by cardiologists, with
      potentially fatal consequences. Herein, we present a case study in order to draw
      attention to cardiac beriberi. We believe that this case will be helpful for
      young cardiologists, reminding them of the importance of this forgotten but
      memorable disease. 

PMID- 24044019
TI  - Takotsubo cardiomyopathy associated with severe hypocalcemia secondary to
      idiopathic hypoparathyroidism.
AB  - The etiology and pathophysiology of takotsubo cardiomyopathy have not yet been
      fully clarified. We report a case of takotsubo cardiomyopathy associated with
      severe hypocalcemia secondary to hypoparathyroidism. A 69-year-old woman
      presented with acute pulmonary edema caused by severe left ventricular
      dysfunction with apical ballooning compatible with takotsubo cardiomyopathy.
      Laboratory tests revealed severe hypocalcemia secondary to idiopathic
      hypoparathyroidism. Coronary angiography showed normal coronary artery function.
      Her symptoms and signs of heart failure improved dramatically with the correction
      of hypocalcemia through calcium and calcitriol replacement. 

PMID- 24044020
TI  - A rare congenital anomaly: interrupted aortic arch and giant ascending aortic
      aneurysm in a young male.

PMID- 24044022
TI  - New insights into public perceptions of cancer.
AB  - A survey was conducted to identify perceptions of cancer and its treatment among
      the general public, patients, and care givers in six countries. The purpose of
      the research-the PACE Cancer Perceptions Index (2012)-was to share public
      perspective on the progress of cancer care and treatment with stakeholders who
      make decisions about cancer innovation and access to treatments in order to allow
      patient-centric decisions. The results revealed that although understanding of
      cancer is increasing, a number of misconceptions persist. Although most
      respondents recognise that progress has been made in cancer treatment and a
      majority express satisfaction with this progress, they nevertheless want more
      investment and faster access to new cancer treatments. In particular, there was
      clear agreement that more collaboration was needed across countries and between
      the various stakeholders within countries. In addition, a clear majority of
      respondents does not think that their country invests sufficient funds in cancer
      research, and there is concern that progress may be jeopardised by the current
      difficult economic times. 

PMID- 24044023
TI  - Phosphorylation of Tip60 Tyrosine 327 by Abl Kinase Inhibits HAT Activity through
      Association with FE65.
AB  - The transfer of acetyl groups from acetyl coenzyme A to the epsilon amino group
      of internal lysine residues is catalyzed by Tip60, which is in the MYST family of
      nuclear histone acetyltransferases (HATs). The tyrosine phosphorylation of Tip60
      seems to be a unique modification. We present evidence that Tip60 is modified on
      tyrosine 327 by Abl kinase. We show that this causes functional changes in HAT
      activity and the subcellular localization of TIP60, which forms a complex with
      Abl kinase. The Tip60 mutation Y327F abolished tyrosine phosphorylation, reduced
      the inhibition of Tip60 HAT activity, and caused G0-G1 arrest and association
      with FE65. Thus, our findings for the first time suggested a novel regulation
      mechanism of Tip60. Regulation was through phosphorylation of tyrosine 327 by Abl
      tyrosine kinase and depended on environmental conditions, suggesting that the
      tyrosine residue of Tip60 is important for the activation process. 

PMID- 24044024
TI  - A Predictive Model of Anesthesia Depth Based on SVM in the Primary Visual Cortex.
AB  - In this paper, a novel model for predicting anesthesia depth is put forward based
      on local field potentials (LFPs) in the primary visual cortex (V1 area) of rats.
      The model is constructed using a Support Vector Machine (SVM) to realize
      anesthesia depth online prediction and classification. The raw LFP signal was
      first decomposed into some special scaling components. Among these components,
      those containing higher frequency information were well suited for more precise
      analysis of the performance of the anesthetic depth by wavelet transform.
      Secondly, the characteristics of anesthetized states were extracted by complexity
      analysis. In addition, two frequency domain parameters were selected. The above
      extracted features were used as the input vector of the predicting model.
      Finally, we collected the anesthesia samples from the LFP recordings under the
      visual stimulus experiments of Long Evans rats. Our results indicate that the
      predictive model is accurate and computationally fast, and that it is also well
      suited for online predicting. 

PMID- 24044025
TI  - A functional mathematical model to simulate the single-breath nitrogen washout.
AB  - A nonlinear dynamic model is proposed to reproduce and interpret the influence of
      pulmonary inhomogeneities on the single-breath nitrogen washout (SBNW) curve. The
      model is characterized by two parallel zones. In each zone, the upper airways are
      described by a Rohrer resistor. Intermediate airways are represented as a
      collapsible segment, the volume of which depends on transmural pressure. Smaller
      airways are described by a resistance which increases when transpulmonary
      pressure decreases. The respiratory region is modeled as a Voigt element. Three
      different conditions were simulated: a reference case, characterized by airway
      parameter values for normal conditions, and two pathological states corresponding
      to different levels of disease. In the reference case, a straight line was a good
      approximation of SBNW phase III and the last point of departure of the nitrogen
      trace from this line unambiguously identified the onset of phase IV. The slope of
      phase III rose with disease severity (from a 1.1% increase in nitrogen
      concentration per 1000 ml of expired volume in the reference case to 3.6% and
      7.7% in the pathological cases) and the distinction between phases III and IV
      became less evident. The results obtained indicate that the slope of phase III
      depends primarily on nitrogen-concentration differences between lung zones, as
      determined by different mechanical properties of the respiratory airways. In
      spite of the simplified representation of the lungs, the similarity of the
      simulation results to actual data suggests that the proposed model describes
      important physiological mechanisms underlying changes observed during SBNW in
      normal and pathological patients. 

PMID- 24044026
TI  - An Unusual Case of Fibromuscular Dysplasia with Bilateral Renal Macroaneurysms:
      Three-year Outcome After Endovascular Treatment.
AB  - Fibromuscular dysplasia (FMD) is an idiopathic, segmental, non-inflammatory and
      non-atherosclerotic disease that affects arterial walls, leading to stenosis of
      small and medium-sized arteries. FMD mostly involves renal and intracranial
      arteries and only in few patients is associated with macroaneurysms (RAAs). We
      present the case of a 45-years old woman with recent history of grade 2
      hypertension that suffered of subarachnoid haemorrhage due to rupture of a
      basilar artery aneurysm. The cerebral aneurysm was immediately treated by coil
      embolization and an abdominal angio-CT scan was performed to investigate the
      presence of renovascular hypertension. The exam showed the presence of FMD of the
      renal arteries associated with presence of bilateral RAAs. Due to the high risk
      of rupture, the bigger aneurysm (2,5 cm diameter) present on the left artery was
      immediately treated by coil embolization. The fusiform aneurysm, present on the
      right renal artery, was instead treated one year later by using two flow diverter
      stents. After three years, an angiographic study showed that both cerebral and
      renal aneurysms were excluded from the blood flow without evidence of arterial
      restenosis. 

PMID- 24044027
TI  - Relationship between Cognitive Function, Depression/Anxiety and Functional
      Parameters in Patients Admitted for Congestive Heart Failure.
AB  - Cognitive impairment, anxiety and depression have been described in patients with
      congestive heart failure (CHF). We analyzed in-hospital CHF patients before
      discharge with neuropsychological tests attempting to correlate with prognostic
      parameters. METHODS: All subjects underwent a mini mental state examination
      (MMSE), geriatric depression scale (GDS), anxiety and depression scale test
      (HADS). We evaluated NYHA class, brain natriuretic peptide (BNP), left
      ventricular ejection fraction (LVEF) and non-invasive cardiac output (CO).
      RESULTS: Three-hundred and three CHF patients (age 71.6 ys) were analysed. The
      mean NYHA class was 2.9+/-0.8, LVEF was 43.4+/-15.8%; BNP plasma level and CO
      were calculated as 579.8+/-688.4 pg/ml and 3.9+/-1.1 l/min, respectively. In 9.6%
      a pathological MMSE score emerged; a depression of mood in 18.2% and anxiety in
      23.4% of patients were observed. A significant correlation between MMSE and age
      (r=0.11 p=0.001), BNP (r=0.64 p=0.03) but not between MMSE and NYHA class and
      LVEF was observed. GDS and HADS were inversely correlated with NYHA class (r=0.38
      p=0.04) and six-minute walking test (r=0.18 p=0.01) without an association with
      objective parameters in CHF (BNP, LVEF and cardiac output). At multivariate
      analysis only MMSE and BNP are inversely correlated significantly (p=0.019 OR=
      0.64, CI=-042-0.86). CONCLUSIONS: in-hospital CHF patients may manifest a
      reduction of MMSE and important anxiety/depression disorders. The results of the
      study suggest that the presence of cognitive impairment in older CHF patients
      with higher BNP plasma level should be considered. In admitted CHF patients
      anxiety and depression of mood are commonly reported and influenced the
      perception of the severity of illness.

PMID- 24044028
TI  - Is there evidence of early vascular disease in patients with obstructive sleep
      apnoea without known comorbidities? Preliminary findings.
AB  - We evaluated early atherosclerotic lesions in 20 non-smokers with newly diagnosed
      Obstructive Sleep Apnoea (OSA) and without known comorbidities by measuring
      common carotid artery intima media thickness (CCA-IMT), transcranial Doppler
      ultrasound (TCD), and ankle brachial index (ABI). These were compared with 20
      healthy age- and BMI-matched controls. In OSA patients, CCA-IMT was not
      significantly higher vs. controls (0.74+/-0.17 vs. 0.66+/-0.12 mm, p=0.201) and
      it was positively correlated with neck circumference (r=0.466, p=0.039), arousal
      index (r=0.663, p=0.001), gamma-glutamyl transpeptidase activity (r=0.474,
      p=0.035) while it was negatively correlated with Forced Expiratory Volume in 1
      sec (r=-0.055, p=0.012). No difference was noted between patients and controls in
      terms of vascular stenosis on TCD examination, while asymptomatic peripheral
      artery disease was found in one patient with OSA. In conclusion, OSA patients
      without known comorbidities exhibit a non-significant increase in CCA-IMT without
      further evidence of vascular disease, but additional experience in a larger
      patient series is needed. 

PMID- 24044029
TI  - Comparative Effects of Preoperative Angiotensin-converting Enzyme In-hibitor,
      Statin and Beta-blocker Treatment on Human Internal Mammary Artery Reactivity in
      Patients with Coronary Artery Disease: A Pilot Study.
AB  - PURPOSE: We investigated the effect of angiotensin-converting enzyme (ACE)-
      inhibitor, statin, and beta-blocker usage before coronary bypass surgery (CABG)
      on vascular reactivity of the internal mammary artery (IMA). METHODS: Patients,
      who underwent elective CABG were evaluated. Samples of IMA obtained from 22
      patients were divided into 4 groups in respect of drugs used by patients before
      bypass surgery (control group, ACE inhibitor + statin group, ACE inhibitor +
      statin + beta-blocker group, and ACE inhibitor + beta-blocker group). The
      discarded, distal end section of IMA was carefully removed, and the
      vasoreactivity of IMA rings was evaluated in vitro using an organ chamber. Smooth
      muscle contractile function was tested on artery segments exposed to 10-80 mM KCl
      and norepinephrine. The endothelial function of IMA rings was assessed with
      acetylcholine (ACh) and bradykinin, while endothelium-independent vasorelaxation
      was evaluated by sodium nitroprusside (SNP). RESULTS: Both ACh and bradykinin
      caused concentration-dependent relaxation in endothelium-intact IMA rings.
      However, the maximal effect produced by endothelium-dependent agents in all
      treatment groups was more prominent when compared with the control group. There
      was no significant difference in the endothelium-dependent relaxation response of
      IMA between ACE inhibitor + statin, ACE inhibitor + beta-blocker and ACE
      inhibitor + statin + beta-blocker groups. The vasodilatory potency of SNP was
      similar in all groups. Similarly, contractile response to KCl or norepinephrine
      was not significantly different between groups. CONCLUSION: Use of ACE inhibitors
      and statins before bypass surgery may influence IMA vasoreactivity by improving
      endothelial control of vascular tone.

PMID- 24044030
TI  - Use of Ultrasonic Bone Surgery (Piezosurgery) to Surgically Treat Bisphosphonate
      Related Osteonecrosis of the Jaws (BRONJ). A Case Series Report with at Least 1
      Year of Follow-Up.
AB  - This preliminary work documents the use of a powerful piezosurgery device to
      treat biphosphonate-related osteonecrosis of the jaw (BRONJ) in combination with
      classical medication therapy. Eight patients presenting 9 BRONJ sites were
      treated, 2 in the maxilla and 7 in the mandible. Reason for biphosphonate (BiP)
      intake was treatment of an oncologic disease for 5 patients and osteoporosis for
      3. The oncologic and osteoporosis patients were diagnosed with BRONJ after 35-110
      months and 80-183 months of BiP treatment, respectively. BRONJ 2 and 3 was found
      in 4 patients. Resection of the bone sequestrae was performed with a high power
      ultrasonic (piezo) surgery and antibiotics were administrated for 2 weeks. Soft
      tissue healing was incomplete at the 2-week control but it was achieved within 1
      month. At the 1-year control, soft tissue healing was maintained at all patients,
      without symptom recurrence. One patient with paraesthesia had abated; of the 2 pa
      tients with trismus, one was healed, severity of the second trismus abated. This
      case report series suggests that bone resection performed with a high power
      ultrasonic surgery device combined with antibiotics might lead to BRONJ healing.
      More patients are warranted to confirm the present findings and assess this
      treatment approach. 

PMID- 24044031
TI  - The Relationship Between Function and Disease Activity as Measured by the HAQ and
      DAS28 Varies Over Time and by Rheumatoid Factor Status in Early Inflammatory
      Arthritis (EIA). Results from the CATCH Cohort.
AB  - OBJECTIVE: To investigate the relationship between function and disease activity
      in early inflammatory arthritis (EIA). METHODS: Canadian Early Arthritis Cohort
      (CATCH) (n=1143) is a multi-site EIA cohort. Correlations between the Health
      Assessment Questionnaire Disability Index (HAQ) and DAS28 were done at every 3
      months for the first year and then at 18 and 24 months. We also investigated the
      relationship between HAQ and DAS28 by age (<65 versus >=65) and RF (positive vs
      negative). RESULTS: Mean HAQ and DAS28 scores were highest at the initial visit
      with HAQ decreasing over 24 months from a baseline of 0.94 to 0.40 and DAS28
      scores decreasing from 4.54 to 2.29. All correlations between HAQ and DAS28 were
      significant at all time points (p<0.01). The correlations between HAQ and DAS28
      were variable over time. The strongest correlation between HAQ and DAS28 occurred
      at initial visit (most DMARD naive) (n=1,143) and 18 months (r=0.57, n=321) and
      24 months (r=0.59, n=214). The baseline correlation between HAQ and DAS28 was
      significantly different than correlations obtained at 3, 6, and 12 months
      (p=0.02, 0.01, and 0.01, respectively). Age did not change the association
      between HAQ and DAS28 {<65 years old (r=0.50, n=868) versus >=65 (r=0.48, n=254),
      p=0.49}. The correlation between HAQ and DAS28 was stronger with RF+ patients
      (r=0.63, n=636) vs RF negative (r=0.47, n=477), p=0.0043. CONCLUSION: Over 2
      years in EIA, HAQ and DAS both improved; correlations at time points were
      different over 2 years and RF status affected the correlations.

PMID- 24044032
TI  - Meanings over time of working as a nurse in elderly care.
AB  - BACKGROUND: Although registered nurses (RNs) play a central role in the care of
      older persons, their work in elderly care has historically been described as "low
      status" in nursing. This is especially problematic due to the global issue of RN
      turnover, but there is still little evidence of how to change this trend. Better
      understanding is needed of the reasons why RNs work in elderly care, as well as
      knowledge of whether these reasons have changed over time. AIM: The aim was to
      explore the meaning of working in elderly care, over time, from the perspective
      of RNs. METHOD: We interviewed thirteen RNs working in nursing homes, six of them
      in 2000 and the remaining seven in 2012, and analysed the resulting data using
      Interpretive Description. RESULTS: The results show similarities and differences
      over time in the RNs' reasoning about the meaning of their work with older
      persons, from a focus on obstacles to a view of opportunities. CONCLUSION: An
      RN's intention to continue working in elderly care might be based on their
      beliefs; their view of older people, and their experiences of being able to
      influence the care. Managing this knowledge could be an essential factor in
      reversing the historical trend of RN work in elderly care being seen as low
      status, and the increasing turnover in such nurses. Our results could stimulate
      reflection on daily care and beliefs about caring for older persons.

PMID- 24044034
TI  - The effect of topical capsaicin-induced sensitization on heat-evoked cutaneous
      vasomotor responses.
AB  - Brief, localized, cutaneous, non-painful thermal stimuli can evoke a transient
      vasomotor response, causing increased cutaneous blood flow and elevated skin
      temperature. The aims of this study were to investigate 1) if cutaneous
      sensitization by topical application of capsaicin (TRPV1 receptor agonist) can
      facilitate the size, duration and spatial extent of this vasomotor response and
      2) if males and females respond differently. Thermal pulses (43 degrees C for 60
      seconds) were applied on left/right volar forearms of 15 age-matched males and
      females. Skin temperature and cutaneous blood flow were measured 1, 5, 10, 15,
      and 30 minutes after heat application before and after topical capsaicin (1%, 30
      min application) with contralateral arm serving as the control. Recordings were
      made from the region of interest at distances of 2, 4, 6, 8, and 10 cm from the
      capsaicin application site. Sensitization significantly enhanced skin temperature
      for up to 30 min and compared with non-sensitized skin at 10 min. Females showed
      the strongest response after sensitization, but the response lasted longer and
      spread more widely in males. The blood flow responses were significantly longer
      after capsaicin (from 5 to 30 minutes after thermal application). This increased
      blood flow extended outside the treated area up to 10 min after stimulation.
      After sensitization, the area under the blood flow response curves showed
      significantly stronger responses in females, spreading 4 cm outside the
      stimulation site. Cutaneous sensitizing caused prolonged and spatially expanded
      vasomotor responses to standardized thermal stimulation with sex specific
      differences. 

PMID- 24044033
TI  - Neuropathogenesis of HIV-1-associated neurocognitive disorders: a possible
      involvement of D-serine.
AB  - A unique feature of N-methyl-D-aspartate receptors (NMDARs) that distinguishes
      them from other ionic receptors is that their activation requires more than one
      agonist to bind simultaneously to distinct binding sites on the receptor. D
      serine, a co-agonist binding to the glycine site of NMDARs, has been implicated
      in several NMDAR-dependent physiological processes, and altered D-serine levels
      under certain pathophysiological conditions contribute to neural dysfunction via
      NMDARs in the central nervous system. Entry of HIV-1 in the brain causes neuronal
      injury leading to cognitive, behavioral and motor impairments known as HIV
      associated neurocognitive disorders (HAND). As HIV-1 does not infect neurons,
      neuronal injury is believed to be primarily mediated by an indirect
      mechanism,that is, HIV-1-infected and/or immune-activated macrophages and
      microglial cells release soluble molecules leading to neuronal injury or death.
      Among the soluble factors is D-serine. In this article we try to address recent
      progresses on the role D-serine might play in the pathogenesis of
      neurodegenerative disorders with a particular emphasis of the involvement of D
      serine in HIV-1-associated neurotoxicity. 

PMID- 24044035
TI  - Modulation of nicotinic acetylcholine receptors in native sympathetic neurons by
      ethanol.
AB  - OBJECTIVE: To determine whether actions on nicotine acetylcholine receptors
      (nAChRs) contribute to ethanol's depressant effects on the autonomic nervous
      system. METHODS: The acute effects of ethanol on nAChRs were examined in primary
      cultured superior cervical ganglion (SCGs) by whole-cell patch clamp recordings.
      After the whole-cell configuration was formed, drugs diluted to various
      concentrations with extracellular solution were applied directly to single
      neurons. RESULTS: Held at -70 mV, ethanol significantly and reversibly inhibited
      nicotine-evoked currents (INic) with a maximum inhibition rate of ~80% and an
      IC50 of 232.88+/-40.66 mM. At 50 mM, ethanol accelerated the slow decay, but did
      not affect the quick decay and rising time of INic. There was neither use
      dependence nor voltage-dependence of ethanol on suppressing INic in SCGs.
      CONCLUSION: Ethanol inhibited the whole-cell INic significantly,probably through
      noncompetitive inhibition at the binding sites outside of the cell membrane.

PMID- 24044036
TI  - Regulation of GABAA receptors by fragile X mental retardation protein.
AB  - Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation
      protein (FMRP). The deficiency of GABAA receptors (GABAARs) is implicated in FXS.
      However, the underlying mechanisms remain unclear. To investigate the effect of
      FMRP on GABAARs, we transfected FMRP cDNAs in rat cortical neurons. We measured
      the protein expression of GABAARs and phosphatase PTEN, and recorded GABAAR
      mediated whole-cell currents in the transfected neurons. We show that the
      transfection of FMRP cDNAs causes increased protein expression of GABAARs in
      cortical neurons, but GABAAR-mediated whole-cell currents are not potentiated by
      FMRP transfection. These results suggest the possibility that intracellular
      signaling antagonizing GABAAR activity may play a role in inhibiting GABAAR
      function in FMRP-transfected neurons. We further show that FMRP transfection
      results in an enhanced protein expression of PTEN, which contributes to the
      inhibition of GABAAR function in FMRP-transfected neurons. These results indicate
      that GABAARs are regulated by FMRP through both an up-regulation of GABAAR
      expression and a PTEN enhancement-induced inhibition of GABAAR function,
      suggesting that an abnormal regulation of GABAAR and PTEN by the loss of FMRP
      underlies the pathogenesis of FXS. 

PMID- 24044037
TI  - Role of Hepatocyte Paraffin 1 antigen in the course of colorectal carcinogenesis.
AB  - BACKGROUND: Few studies have reported the expression of Hepatocyte Paraffin 1
      (Hep Par 1) in colorectal carcinomas with contradictory results. Reported rate of
      expression ranged from 4-50%. Moreover, the correlation between Hep Par 1
      expression and clinicopathological parameters has not been investigated. The
      objective of the present study was to investigate the role of CPS1 (using Hep Par
      1) in colonic carcinogenesis and characterize carcinomas which express it.
      MATERIAL AND METHOD: Comparative analysis was done between Hep Par 1 expression
      in normal colonic mucosa (n=10), adenomatous polyps (n=29) and sporadic
      adenocarcinoma (n=40) and was correlated with clinicopathologic parameters.
      RESULTS: Normal colonic mucosa did not express Hep Par 1. In contrast, it was
      expressed in dysplastic glands and neoplastic cells of well-moderately
      differentiated non-mucinous adenocarcinomas. Hep Par 1 was found in 47.5% of
      colonic carcinomas, 41.7% of polyps with high grade dysplasia (HGD) and 23.5% of
      polyps with low grade dysplasia (LGD). Mean Hep Par-1 score, likewise, was
      highest in carcinoma, high in polyps with HGD and lowest in polyps with LGD. Hep
      Par 1 expression inversely correlated with some conventional prognostic
      parameters including tumour type, grade, lymph node metastasis and AJCC stage. It
      did not correlate with depth of invasion or lymphovascular invasion. CONCLUSION:
      Hep Par 1 (i.e. CPS1) might play an active role in initiation of dysplasia and
      progression of multistep colorectal carcinogenesis. However, it seems that CPS1
      is not involved in invasion and tumour spread. Conversely, it might be in the
      play of suppressing cancer progression. These findings could have both prognostic
      and therapeutic applications.

PMID- 24044038
TI  - ERK1/2 in the brain mediates the effects of central resistin on reducing
      thermogenesis in brown adipose tissue.
AB  - We investigated the role of ERK1/2 in the brain on the effects of centrally
      administered resistin on thermogenesis. Resistin (7 MUg) into anaesthetized rats
      significantly decreased brown adipose tissue temperature by 1.0 +/- 0.4  degrees
      C (P < 0.005). This response was significantly attenuated by over 60% when ERK1/2
      was inhibited by U0126 (7 MUg) (P < 0.05). Resistin reduced uncoupling protein-1
      mRNA expression (0.11 +/- 0.01 vs 1.24 +/- 0.85 resistin vs control respectively)
      and the expression of peroxisome proliferator-activated receptor gamma co
      activator 1-alpha, but the effects were not statistically significant. The
      results suggest that ERK1/2 in the brain contributes to resistin's effects on
      thermogenesis. 

PMID- 24044039
TI  - Effects of a single low-dose acetaminophen on body temperature and running
      performance in the heat: a pilot project.
AB  - PURPOSE: To examine the effects of a single low-dose (500 mg) acetaminophen on
      body temperature and running performance in the heat (30  degrees C). METHODS:
      This is a randomized, cross-over pilot study performed in a climatic chamber at
      the Department of Sport Science of the University of Innsbruck. Seven male sport
      students (age, 25.9 +/- 2.3 years; VO2max, 67.3 +/- 7.1 mL/min/kg) participated
      in the study. Each participant performed two prolonged exercise tests at a
      constant intensity on a treadmill at a temperature of 30  degrees C at an
      individual intensity corresponding to 70 % VO2max. Two hours before exercising
      participants were randomly assigned to receive acetaminophen (500 mg) or placebo
      and performed the same test 2 weeks later with reverse pre-treatment. RESULTS:
      After 20 min of running in the heat core temperature increase was less under
      acetaminophen (P = 0.004) and heart rates were higher (P = 0.02) compared to
      placebo. At the end of exercise neither running time nor body temperature nor
      ratings of perceived exertion differed between groups. CONCLUSION: Although the
      increase in core temperature was slightly reduced by acetaminophen after 20
      minutes of running in the heat running performance remained unaffected after pre
      treatment with a single low-dose of acetaminophen.

PMID- 24044040
TI  - Per-oral endoscopic myotomy for achalasia: An American perspective.
AB  - Achalasia is an uncommon esophageal motility disorder characterized by the
      selective loss of enteric neurons leading to absence of peristalsis and impaired
      relaxation of the lower esophageal sphincter. Per-oral endoscopic myotomy (POEM)
      is a novel modality for the treatment of achalasia performed by
      gastroenterologists and surgeons. It represents a natural orifice transluminal
      endoscopic surgery (NOTES) approach to Heller myotomy. POEM has the minimal
      invasiveness of an endoscopic procedure that can duplicate results of the
      surgical Heller myotomy. POEM is conceptually similar to a surgical myotomy
      without the inherent external incisions and post-operative care associated with
      surgery. Initial high success and low complications rates promise a great future
      for this technique. In fact, POEM has been successfully performed on patients
      with end-stage achalasia as an initial treatment reserving esophagectomy for
      those without good response. The volume of POEMs performed worldwide has grown
      exponentially. In fact, surgeons who have performed Heller myotomy have embraced
      POEM as the preferred intervention for achalasia. However, the niche of POEM
      remains to be defined and long term results are awaited. We describe our
      experience with POEM having performed the first POEM outside of Japan in 2009,
      the evolution of our technique, and give our perspective on its future. 

PMID- 24044041
TI  - Hybrid natural orifice transluminal endoscopic surgery in gastric subepithelial
      tumors.
AB  - Diagnosis of gastric subepithelial tumor (SET) has shown a rapid increase
      worldwide. Although, until now, endoscopic ultrasound guided procedures such as
      fine needle aspiration have shown relatively high accuracy in diagnosis of SET,
      the most important modality for diagnosis and treatment of SETs is complete
      resection such as endoscopic or surgical resection. However, endoscopic resection
      or laparoscopic wedge resection alone also has some limitations. Endoscopic
      resection is difficult to perform in cases of gastric SET located within deep
      portion of the gastric layer or a relatively large (larger than 25 mm diameter).
      On the other hand, gastric SET in a difficult location, such as the
      gastroesophageal junction or pyloric ring is challenging for laparoscopic
      surgical resection. The hybrid natural orifice transluminal endoscopic surgery
      (NOTES) technique is a combined method, including the advantages of both
      laparoscopic resection and endoscopic resection for gastric SETs. This method may
      be performed safely with reasonable operation times, less bleeding, and adequate
      resection margin and regardless of tumor size. In particular, in the case of a
      difficult location for resection, such as the esophagogastric junction or pyloric
      ring, hybrid NOTES is currently believed to be an ideal treatment method. 

PMID- 24044042
TI  - Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel
      cleansing for late-morning colonoscopy.
AB  - AIM: To evaluate the efficacy, tolerability, acceptability and feasibility of
      bisacodyl plus low volume polyethyleneglycol-citrate-simeticone (2-L PEG-CS)
      taken the same day as compared with conventional split-dose 4-L PEG for late
      morning colonoscopy. METHODS: Randomised, observer-blind, parallel group,
      comparative trial carried out in 2 centres. Out patients of both sexes, aged
      between 18 and 85 years, undergoing colonoscopy for diagnostic investigation,
      colorectal cancer screening or follow-up were eligible. The PEG-CS group received
      3 bisacodyl tablets (4 tablets for patients with constipation) at bedtime and 2-L
      PEG-CS in the morning starting 5 h before colonoscopy. The control group received
      a conventional 4-L PEG formulation given as split regimen; the morning dose was
      taken with the same schedule of the low volume preparation. The Ottawa Bowel
      Preparation Scale (OBPS) score was used as the main outcome measure. RESULTS: A
      total of 164 subjects were enrolled and 154 completed the study; 78 in the PEG-CS
      group and 76 in the split 4-L PEG group. The two groups were comparable at
      baseline. The OBPS score in the PEG-CS group (3.09 +/- 2.40) and in the PEG group
      (2.39 +/- 2.55) were equivalent (difference +0.70; 95%CI: -0.09-1.48). This was
      confirmed by the rate of successful bowel cleansing in the PEG-CS group (89.7%)
      and in the PEG group (92.1%) (difference -2.4%; 95%CI: -11.40- 6.70). PEG-CS was
      superior in terms of mucosa visibility compared to PEG (85.7% vs 72.4%, P =
      0.042). There were no significant differences in caecum intubation rate, time to
      reach the caecum and withdrawal time between the two groups. The adenoma
      detection rate was similar (PEG-CS 43.6% vs PEG 44.7%). No serious adverse events
      occurred. No difference was found in tolerability of the bowel preparations.
      Compliance was equal in both groups: more than 90% of subjects drunk the whole
      solution. Willingness to repeat the same bowel preparations was about 90% for
      both regimes. CONCLUSION: Same-day PEG-CS is feasible, effective as split-dose 4
      L PEG for late morning colonoscopy and does not interfere with work and daily
      activities the day before colonoscopy.

PMID- 24044043
TI  - Diagnostic utility of small-caliber and conventional endoscopes for gastric
      cancer and analysis of endoscopic false-negative gastric cancers.
AB  - AIM: To analyze the diagnostic utility of a small-caliber endoscope (SC-E) and
      clinicopathological features of false-negative gastric cancers (FN-GCs). METHODS:
      A total of 21638 esophagogastroduodenoscopy (EGD) gastric cancer (GC) screening
      examinations were analyzed. Secondary endoscopic examinations (n = 3352) were
      excluded because most secondary examinations tended to be included in the
      conventional endoscopy (C-E) group. Detection rates of GCs and FN-GCs were
      compared between SC-E and C-E groups. FN-GC was defined as GC performed with EGD
      within the past 3 years without GC detection. Macroscopic types,
      histopathological characteristics and locations of FN-GCs were compared with
      firstly found-gastric cancers (FF-GCs) in detail. RESULTS: SC-E cases (n = 6657)
      and C-E cases (n = 11644), a total of 18301 cases, were analyzed. GCs were
      detected in 16 (0.24%) SC-E cases and 40 C-E (0.34%) cases (P = 0.23) and there
      were 4 FN-GCs (0.06%) in SC-E and 13 (0.11%) in C-E (P = 0.27), with no
      significant difference. FN-GCs/GCs ratio between SC-E and C-E groups was not
      significantly different (P = 0.75). The comparison of endoscopic macroscopic
      types of FN-GCs tended to be a less advanced type (P = 0.02).
      Histopathologically, 70.6% of FN-GCs were differentiated and 29.4%
      undifferentiated type. On the other hand, 43.0% of FF-GCs were differentiated and
      53.8% undifferentiated type, so FN-GCs tended to be more differentiated type (P =
      0.048). CONCLUSION: The diagnostic utility of SC-E for the detection of GCs and
      FN-GCs was not inferior to that of C-E. Careful observation for superficially
      depressed type lesions in the upper lesser curvature region is needed to decrease
      FN-GCs.

PMID- 24044044
TI  - Extremely rare case of primary esophageal mucous associated lymphoid tissue
      lymphoma.
AB  - SJ is a 37-year-old male who presented with one year history of dysphagia,
      odynophagia and 15 pounds weight loss. He underwent endoscopic evaluation which
      showed mid esophageal ulcers. It was thought that the cause of the ulcer was the
      multivitamins and the patient was asked to stop them. Furthermore Esomeprazole
      therapy was also initiated. Patient's symptoms persisted but he did not seek any
      medical attention until about one year later. Meanwhile the patient reported
      additional 15 pounds of weight loss. We repeated upper endoscopy again which
      showed evidence of two chronic non bleeding irregular friable ulcerations seen in
      the mid esophagus, 31 cm from the incisors. Biopsies and frozen section were
      taken and sent for assessment to the Pathology lab. Immunoperoxidase studies on
      frozen sections showed the presence of IgM and for most plasma cells IgG. The
      microscopic and histologic findings were consistent with mucous associated
      lymphoid tissue lymphoma with plasmocytic differentiation. Computed tomographic
      scan done showed no evidence of spread to adjacent structures. The patient was
      referred to oncology and several cycles of radiation and Rituximab therapy were
      initiated which cured the disease. Subsequent endoscopies with blind biopsies
      were done which were negative for any neoplastic process. 

PMID- 24044045
TI  - Pseudoachalasia: A peculiar case report and review of the literature.
AB  - Pseudoachalasia is a rare secondary achalasia, which accounts for only a small
      subgroup of patients. We describe a 77-year-old woman with recent onset of
      dysphagia and typical esophageal manometric findings of achalasia. Moreover,
      esophageal manometric findings of vascular compression at 36 cm from the nose
      were associated with dysphagia. An upper endoscopy showed the absence of lesions
      both in the esophagus and gastro-esophageal junction, whilst a 15-mm ulcer on the
      gastric angulus was detected. The gastric ulcer resulted in being a diffuse
      signet ring cell carcinoma at histology, suggesting pseudoachalasia. An abdominal
      computed tomography scan showed an irregular concentric thickening of the gastro
      esophageal junction wall extending for 7 cm and a dilated ascending thoracic
      aorta with no presence of the inferior vena cava, with an enlarged azygos as the
      source of vascular compression of esophagus. Moreover, cardia involvement from
      diffuse signet ring cell carcinoma of the gastric angulus was also recognized as
      the cause of dysphagia. The cancer was not suitable for a surgical approach in an
      old patient with cardiovascular comorbidities and support therapy was started. In
      our ambulatory series, pseudoachalasia was eventually diagnosed in 4.7% of 234
      consecutive patients with esophageal manometric finding suggestive of achalasia.
      We also reviewed cases in the literature and aimed to evaluate the reported
      causes of pseudoachalasia. 

PMID- 24044046
TI  - Abdominal pain post endoscopic mucosal resection: Treat the patient not the CT
      scan.
AB  - An 85-year-old female, with hereditary nonpolyposis colorectal cancer syndrome,
      underwent a colonoscopy and endoscopic mucosal resection (EMR) of a 25-mm
      proximal ascending colon polyp (Paris classification 0-Is). Post-procedure, the
      patient developed abdominal pain in the right iliac fossa which settled 1 h
      later. An urgent computed tomography (CT) scan of her abdomen was organised which
      happened 6 h post onset of abdominal pain. She had radiological evidence of
      perforation on the CT scan but clinically remained well and was managed
      conservatively. The exact aetiology of this patient's symptoms is not known. We
      suspect the radiological findings are probably due to a combination of injectate
      within the colonic wall and leakage of insufflated air or CO2 following
      transmural passage of the EMR needle. As EMR is becoming an increasingly
      effective treatment modality in the management of large sessile polyps,
      clinicians need to be aware of potential complications of treatment. It is also
      important to recognise that radiological features of perforation can be seen post
      EMR in the absence of an EMR associated perforation. 

PMID- 24044047
TI  - Gastric calcifying fibrous tumor removed by endoscopic submucosal dissection.
AB  - The World Health Organization describes calcifying fibrous tumors (CFTs) as rare,
      benign lesions characterized by hypocellular, densely hyalinized collagenization
      with lymphoplasmacytic infiltration. These tumors rarely involve the
      gastrointestinal (GI) tract. A routine endoscopic upper gastrointestinal screen
      detected a 10-mm submucosal tumor (SMT) in the lesser curvature of the lower
      corpus of the stomach of an apparently healthy, 37-year-old woman with no history
      of Helicobacter pylori infection. Endoscopic ultrasonography (EUS) localized the
      internally isoechoic, homogeneous SMT mainly within the submucosa. Malignancy was
      ruled out using endoscopic submucosal dissection (ESD). A pathological
      examination confirmed complete resection of the SMT, and defined a hypocellular,
      spindle-cell tumor with a densely hyalinized, collagenous matrix, scattered
      lymphoplasmacytic aggregates as well as a few psammomatous, dystrophic calcified
      foci. The mass was immunohistochemically positive for vimentin and negative for
      CD117 (c-kit protein), CD34, desmin, smooth muscle actin (SMA) and S100.
      Therefore, the histological findings were characteristic of a CFT. To date, CFT
      resection by ESD has not been described. This is the first case report of a
      gastric calcifying fibrous tumor being completely resected by ESD after
      endoscopic ultrasonography. 

PMID- 24044049
TI  - Use of enhancement algorithm to suppress reflections in 3-D reconstructed capsule
      endoscopy images.
AB  - In capsule endoscopy (CE), there is research to develop hardware that enables
      ''real'' three-dimensional (3-D) video. However, it should not be forgotten that
      ''true'' 3-D requires dual video images. Inclusion of two cameras within the
      shell of a capsule endoscope though might be unwieldy at present. Therefore, in
      an attempt to approximate a 3-D reconstruction of the digestive tract surface, a
      software that recovers information-using gradual variation of shading-from
      monocular two-dimensional CE images has been proposed. Light reflections on the
      surface of the digestive tract are still a significant problem. Therefore, a
      phantom model and simulator has been constructed in an attempt to check the
      validity of a highlight suppression algorithm. Our results confirm that 3-D
      representation software performs better with simultaneous application of a
      highlight reduction algorithm. Furthermore, 3-D representation follows a good
      approximation of the real distance to the lumen surface. 

PMID- 24044048
TI  - Uncomplicated spontaneous rupture of pancreatic pseudocyst into stomach: A case
      report.
AB  - Pseudocysts of the pancreas are not rare, but spontaneous perforation and/or
      fistulization occurs in fewer than 3% of these pseudocysts. Perforation into the
      free peritoneal cavity, stomach, duodenum, colon, portal vein, pleural cavity and
      through the abdominal wall has been reported. Spontaneous rupture of the
      pancreatic pseudocyst into the surrounding hollow viscera is rare and, may be
      associated with life-threatening bleeding. Such cases require emergency surgical
      intervention. Uncomplicated rupture of pseudocyst is an even rarer occurrence. We
      present a case of spontaneous resolution of a pancreatic pseudocyst with gastric
      connection without bleeding. A 67-year-old women with a large pancreatic
      pseudocyst resulting from a complication of chronic pancreatitis was referred to
      our institution. During hospital stay, there was sudden decrease in the size of
      epigastric lump. Repeat computed tomography (CT) revealed that the size of the
      pseudocyst had decreased significantly; however, gas was observed in stomach and
      pseudocyst along with rent between lesser curvature of stomach and pseudocyst
      suggestive of spontaneous cystogastric fistula.The fistula tract occluded
      spontaneously and the patient recovered without any complication or need for
      surgical treatment. After 5 wk, follow up CT revealed complete resolution of
      pseudocyst. Esophagogastroduodenoscopy revealed that the orifice was completely
      occluded with ulcer at the site of previous fistulous opening. 

PMID- 24044050
TI  - Structure-activity studies of divin: an inhibitor of bacterial cell division.
AB  - We describe the synthesis and SAR studies of divin-a small molecule that blocks
      bacterial division by perturbing the assembly of proteins at the site of cell
      septation. The bacteriostatic mechanism of action of divin is distinct from other
      reported inhibitors of bacterial cell division and provides an opportunity for
      assessing the therapeutic value of a new class of antimicrobial agents. We
      demonstrate a convenient synthetic route to divin and its analogs, and describe
      compounds with a 10-fold increase in solubility and a 4-fold improvement in
      potency. Divin analogs produce a phenotype that is identical to divin, suggesting
      that their biological activity comes from a similar mechanism of action. Our
      studies indicate that the 2-hydroxynaphthalenyl hydrazide portion of divin is
      essential for its activity and that alterations and substitution to the
      benzimidazole ring can increase its potency. The SAR study provides a critical
      opportunity to isolate drug resistant mutants and synthesize photoaffinity probes
      to determine the cellular target and biomolecular mechanism of divin.

PMID- 24044053
TI  - The need for holistic cancer care framework: breast cancer care as an example.

PMID- 24044051
TI  - In vitro selection of BNA (LNA) aptamers.
AB  - Recently, we achieved the first in vitro selection of 2'-O,4'-C-methylene
      bridged/locked nucleic acid (2',4'-BNA/LNA) aptamers. High-affinity thrombin
      binding aptamers (TBAs) were obtained from DNA-based libraries containing 2'-O,4'
      C-methylene-bridged/linked bicyclic ribonucleotides (B/L nucleotides) in the 5'
      primer region, using the method of capillary electrophoresis systematic evolution
      of ligands by exponential enrichment (CE-SELEX). Furthermore, a similar selection
      protocol could provide TBAs that contain B/L nucleotides in both primer and
      random regions. We review technical challenges involved in the generation of
      various BNA libraries using analogs of B/L nucleoside-5'-triphosphate and
      polymerase variants and also discuss applications of these libraries to the
      selection of BNA (LNA) aptamers, as well as future prospects for their
      therapeutic and diagnostic uses. 

PMID- 24044052
TI  - Rapid genotyping using pyrene-perylene locked nucleic acid complexes.
AB  - We have developed an assay for single strand DNA and RNA detection which is based
      on novel pyrene-perylene FRET pairs attached to short LNA/DNA probes. The assay
      is based on ratiometric emission upon binding of target DNA/RNA by three
      combinations of fluorescent LNA/DNA reporter strands. Specific geometry of the
      pyrene fluorophore attached to the 2'-amino group of 2'-amino-LNA in position 4
      allows for the first time to efficiently utilize dipole-dipole orientation
      parameter for sensing of single-nucleotide polymorphisms (SNPs) in nucleic acid
      targets by FRET. Using novel probes, SNP detection is achieved with advantages of
      large Stokes shift (115 nm), high fluorescence quantum yields and low limit of
      target detection values (< 5 nM). Rapid and accurate genotyping of highly
      polymorphic HIV Pol cDNA and RNA fragments performed herein proves the
      possibility for broad application of the novel pyrene-perylene FRET pairs, e.g.,
      in imaging and clinical diagnostics. 

PMID- 24044054
TI  - Scrotal Dermatitis - Can we Consider it as a Separate Entity?
AB  - Scrotal dermatitis is a very common condition that has been easily overlooked by
      most dermatologists and treating physicians. The condition is easily mistaken for
      the common skin disorders affecting the area, like fungal infections. Scrotal
      dermatitis is not considered a separate disease entity and is usually considered
      a condition similar to the contact dermatitis occurring elsewhere. This article
      attempts to classify the condition as a separate disease entity and explains the
      various etiological factors and the pathogenesis of the condition. The various
      stages of the condition are also explained in detail. Newer treatment modalities
      like the use of narrow band UVB for the management of scrotal dermatitis is also
      highlighted in this article. 

PMID- 24044055
TI  - The effect of intravenous fentanyl on pain and duration of the active phase of
      first stage labor.
AB  - OBJECTIVES: Opioids are most widely used for pain relief during childbirth. An
      alternative opioid, fentanyl, has been shown to be a good option for pain
      management and has fewer side-effects on both mother and fetus. Therefore, the
      purpose of this study is to determine the effect of fentanyl on pain as well as
      the duration of the active phase of labor. METHODS: This clinical trial was
      conducted on 70 multiparous parturients having labor from May to July 2006 at
      Tamin Ejtemai Hospital. They were selected by convenience sampling at the
      beginning of the active phase of labor. The samples were then randomly divided
      into the case and control groups. The case group received fentanyl 50 micrograms
      in two doses, one hour apart after being diluted (0 and 60 mins). Vital signs
      were recorded pre-administration and 5, 15, 30, 45, 60 minutes post
      administration. Pain intensity was estimated by visual pain scale (0-10) four
      times (before and 1, 2, 3 hours after the intervention). Data analysis was done
      using the student t-test, repeated measure ANOVA and chi-square tests via SPSS
      11.5 software. RESULTS: The results showed a significant reduction in pain
      (p=0.002) and HR (p=0.001) in the case group. The mean pain score also decreased
      from 8+/-1 to 5+/-1. There was a significant difference in terms of the duration
      of the active phase between the two groups (p=0.001). However, there were no
      significant differences in terms of systolic blood pressure and diastolic blood
      pressure between the two groups. CONCLUSION: Fentanyl provides good analgesic
      effect for pain management during labor by considerably reducing the duration of
      the active phase, and can therefore be used as an acceptable analgesic agent
      during labor.

PMID- 24044056
TI  - Malignant skin tumors in benin city, South-South, Nigeria.
AB  - OBJECTIVE: Malignant skin tumors rank amongst the most common forms of cancer
      worldwide and constitute a major challenge in dermatopathology and oncology
      research. This study aims to determine the frequency and patterns of malignant
      skin tumors at the University of Benin Teaching Hospital, Benin City, Nigeria.
      METHODS: A 25-year (1982-2007) retrospective study of surgical day books and
      slides of all patients presenting with skin lesions was conducted at the Surgical
      and Pathology Departments of University of Benin Teaching Hospital. RESULTS: A
      total of 694 skin biopsies were seen at the department during the study period;
      of these, 187 cases were malignant constituting 27% of all skin lesions. The
      majority of the malignant skin tumors (48%) occurred between the third and fifth
      decades with a male to female ratio of 1.4:1 and a mean age of 47 +/- 29 years.
      Malignant melanoma was the most common skin malignancy, accounting for (n=61;
      33%). Kaposi sarcoma constituted the second majority of the cases (n=56; 30%),
      with a markedly increased incidence between 2000 and 2008. This was consecutively
      followed by squamous cell carcinoma (n=45; 24%), basal cell carcinoma (n=18; 10%)
      and dermatofibrosarcoma protuberans (n=7; 4%). The leg and foot were the most
      common sites for malignant skin tumors. CONCLUSION: Malignant melanoma was the
      most common skin malignancy in this study. However, an increasing incidence of
      all malignant skin tumors was observed. This was particularly noticeable with
      Kaposi sarcoma, which may be attributed to the increasing prevalence of HIV/AIDS
      in Nigeria.

PMID- 24044057
TI  - Prevalence and Determinants of Pre-Hypertension among Omani Adults Attending Non
      Communicable Disease Screening Program in Primary Care Setting in Sohar City.
AB  - OBJECTIVES: To estimate the prevalence of pre-hypertension and its association
      with some selected cardiovascular risk factors among the Omani adult population
      in the primary healthcare setting. METHOD: A cross-sectional study involving a
      sample taken from a National Screening Program of chronic non-communicable
      diseases in primary healthcare institutions, Sohar city, Sultanate of Oman (July
      2006 - December 2007). Inclusion criteria included Omanis aged 40 years or above
      residents of Sohar city attending primary healthcare institutions not previously
      diagnosed with diabetes mellitus, hypertension, or chronic kidney diseases.
      Descriptive statistics were used to describe the demographic, physical and
      metabolic characteristics. Univariate analysis was used to identify the
      significant association between the characteristics and normal blood pressure,
      pre-hypertension and hypertension. Chi-squared test was used for categorical
      variables analysis and independent t-test was used for continuous variables
      analysis. In order to examine the strength of significant associations, the
      multinomial logistic regression analysis was used. RESULTS: There were 1498
      participants, 41% were males and 59% were females. Overall, pre-hypertension was
      observed in 45% of the total study population (95% CI: 0.422 - 0.473). There were
      more males affected than females (46% versus 44%). About 34% of the total study
      population was hypertensive. The multinomial logistic regression analysis
      revealed that an increase of one unit of age, body mass index, fasting blood
      glucose and total blood cholesterol, were significantly associated with higher
      risk in both pre-hypertension and hypertension. High odds ratio of pre
      hypertension and hypertension was found with the total blood cholesterol.
      CONCLUSION: The prevalence of pre-hypertension was high among the Omani adult
      population. The determinants of pre-hypertension in this research age, body mass
      index, fasting blood glucose and total blood cholesterol. A cost-effectiveness
      study about the management of pre-hypertension within primary healthcare is
      significant in the future health system service strategies.

PMID- 24044058
TI  - A study assessing public knowledge, belief and behavior of antibiotic use in an
      omani population.
AB  - OBJECTIVE: This study was aimed to assess public knowledge, belief and behavior
      towards antibiotics use in a general population in the Sultanate of Oman.
      METHODS: A 12-item self-administered questionnaire was distributed to 850
      prospective participants by researchers using quota sampling in two governorates
      of Oman. The data obtained were evaluated to assess the responses to individual
      questions related to knowledge, belief and behavior of antibiotic use. Median
      score of the respondents was correlated with participant demographics and status
      on use of antibiotics. RESULTS: A total of 718 completed questionnaires were
      obtained giving a response rate of 85%. The median total score of the
      participants was 16 (Interquartile range: 6) out of a possible maximum score of
      24. A moderate knowledge and behavior score was observed, while the belief score
      of the participants was low. A significant difference was observed in the median
      total score based on age group, educational qualification and employment status.
      CONCLUSION: Antibiotics are frequently used by the public. An inappropriate
      belief on antibiotic related aspects was observed and inappropriate behavior was
      noticed, which are reflections of insufficient knowledge and wrong beliefs.
      Interventions must be put in place to educate the public on appropriate
      antibiotic use.

PMID- 24044059
TI  - Noise-induced hearing loss among quarry workers in a north-eastern state of
      malaysia: a study on knowledge, attitude and practice.
AB  - OBJECTIVES: Noise is known to be one of the environmental and occupational
      hazards listed in the Factory and Machinery Act 1967. Quarries with loud
      deafening sounds from trucks and machineries pose the risk of noise-induced
      hearing loss to workers. This study was designed to assess the knowledge,
      attitude and practice towards noise-induced hearing loss and to determine the
      prevalence of noise-induced hearing loss and its associated factors among quarry
      workers in a north-eastern state of Malaysia. METHODS: A cross-sectional study
      was conducted at six quarries in a north-eastern state of Malaysia, with 97
      consented respondents who answered a validated version of a questionnaire and
      underwent pure tone audiogram. The respondents were male, aged between 18 to 50
      years, working in the quarry area for at least 6-months duration with no family
      history of ear diseases. RESULTS: The mean percentage scores of knowledge,
      attitude and practice were 44 (11), 70 (10) and 28 (16) percent, respectively.
      The prevalence of noise-induced hearing loss was found to be 57 (95% CI: 47, 67)
      with 46 (84%) having mild and moderate noise-induced hearing loss, and 34 (62%)
      involved both ears. Multiple logistic regressions showed that age and practice
      score were the associated factors with odd ratios of 1.1 (95% CI: 1.1, 1.2;
      p<0.001) and 0.9 (95% CI: 0.8, 1.0; p=0.008), respectively. CONCLUSION: The
      knowledge, attitude and practice scores of the respondents were poor and the high
      prevalence of noise-induced hearing loss was contributed by factors such as poor
      practice and old age.

PMID- 24044060
TI  - Urinary bladder cancer in yemen.
AB  - OBJECTIVES: The aims of this study are to highlight the clinicopathological
      features of urinary bladder cancer in Yemen, and to describe the histological
      grading of urothelial neoplasms according to the World Health Organization and
      International Society of Urologic pathology (WHO/ISUP 1998) classification.
      METHODS: This is a descriptive record-based study of 316 cases of bladder cancer
      diagnosed by two pathologists at the Department of pathology, Sana'a University
      from 1(st) January 2005 to 30(th) April 2009. The diagnoses were made on
      hematoxylin and eosin stained sections and categorized according to WHO/ISUP 1998
      classification. RESULTS: Out of 316 urinary bladder cancers, 248 (78%) were
      urothelial neoplasms, 53 (17%) were squamous cell carcinoma, 7 (2%) were
      adenocarcinoma, and 3 (1%) were rhabdomyosarcoma. The remaining cases were
      metastatic carcinomas (n=3), small cell carcinoma (n=1), and non-Hodgkin's
      lymphoma (n=1). The urothelial neoplasms observed were carcinoma in situ 4 (2%),
      papilloma 7 (3%), papillary urothelial neoplasm of low malignant potential 26
      (11%), papillary urothelial carcinoma of low grade 107 (43%), papillary
      urothelial carcinoma of high grade 18 (7%), and non-papillary urothelial
      carcinoma of high grade 85 (34%), with 60 years mean age for males and 58 years
      for females; along with a male to female ratio of 4:1. The peak incidence was
      observed in the 61-70 years age group. CONCLUSION: This study documents a high
      frequency of urothelial neoplasms, mostly papillary urothelial carcinoma of low
      grade and non-papillary urothelial carcinoma of high grade with male
      preponderance and peak incidence in 6(th) decade of age.

PMID- 24044061
TI  - The Phenotype/Genotype Correlation of Lactase Persistence among Omani Adults.
AB  - OBJECTIVE: To examine the correlation of lactase persistence phenotype with
      genotype in Omani adults. METHODS: Lactase persistence phenotype was tested by
      hydrogen breath test in 52 Omani Adults using the Micro H2 analyzer. Results were
      checked against genotyping using direct DNA sequencing. RESULTS: Forty one
      individuals with C/C-13910 and T/T-13915 genotypes had positive breath tests
      (>=20 ppm); while eight of nine individuals with T/C-13910 or T/G-13915 genotypes
      had negative breath tests (<20 ppm) and two subjects were non-hydrogen producers.
      The agreement between phenotype and genotype using Kappa value was very good
      (0.93). CONCLUSION: Genotyping both T/C-13910 and T/G-13915 alleles can be used
      to assist diagnosis and predict lactose intolerance in the Omani population.

PMID- 24044062
TI  - The effect of intradialytic aerobic exercise on dialysis efficacy in hemodialysis
      patients: a randomized controlled trial.
AB  - OBJECTIVE: This study was conducted to determine the impact of an 8-week
      intradialytic exercise program (consisting of 15 minutes low-intensity exercise
      during the first 2 hours of dialysis) on dialysis efficacy. METHODS: In an open
      randomized controlled trial, a total of 50 clinically stable hemodialysis
      patients were enrolled into the study and randomly allocated into two groups: the
      aerobic exercise group (n=25) and the control group (n=25). Aerobic exercises
      were done in the intervention group for 15 min/day, three times a week for 2
      months. The dialysis efficacy was assessed prior to and at the end of each month
      of the program. RESULTS: The efficacy of dialysis increased at the end of the
      first month and remained elevated for the duration of the program in the exercise
      group (p<0.05). CONCLUSION: A simplified aerobic exercise program has increased
      the efficacy of dialysis and may be considered as a safe, complementary and
      effective modality for hemodialysis patients.

PMID- 24044063
TI  - Mucinous breast cancer with solitary metastasis to humeral head: a case report.
AB  - Breast cancer is the most common cause of metastatic deposits in the skeleton,
      and bone is the most common site of recurrence of breast cancer. Breast cancer
      metastasis most commonly affects the spine, ribs, pelvis, and proximal long
      bones; however, only 3.5% of breast cancer patients develop long-bone metastases.
      The humerus is the most common upper-extremity site for bony metastasis, and
      pathologic fractures can result. The patient in the current study presented with
      breast cancer and discovered to have humeral head metastasis during initial
      workup. The dilemma was in investigation the modality to confirm humeral head
      metastasis as there are many differential diagnoses with similar findings. After
      staging workup, the patient was treated with neoadjuvant chemotherapy followed by
      modified radical mastectomy and radiotherapy of the chest wall and the shoulder.
      The lesion in humerus was well healed. 

PMID- 24044064
TI  - Successful Treatment of Cardiomyopathy due to Very Long-Chain Acyl-CoA
      Dehydrogenase Deficiency: First Case Report from Oman with Literature Review.
AB  - Very long-chain acyl-CoA dehydrogenase deficiency (MIM 201475) is a severe defect
      of mitochondrial energy production from oxidation of very long-chain fatty acids.
      This inherited metabolic disorder often presents in early neonatal period with
      episodes of symptomatic hypoglycemia usually responding well to intravenous
      glucose infusion. These babies are often discharged without establishment of
      diagnosis but return by 2-5 months of age with severe and progressive cardiac
      failure due to hypertrophic cardiomyopathy with or without hepatic failure and
      steatosis. An early diagnosis and treatment with high concentration medium chain
      triglycerides based feeding formula can be life saving in such patients. Here, we
      report the first diagnosed and treated case of Very long-chain acyl-CoA
      dehydrogenase deficiency in Oman. This infant developed heart failure with left
      ventricular dilation, hypertrophy and pericardial effusion at the age of 7 weeks.
      Prompt diagnosis and subsequent intervention with medium chain triglycerides
      based formula resulted in a reversal of severe clinical symptoms with significant
      improvement of cardiac status. This treatment also ensured normal growth and
      neurodevelopment. It is stressed that the disease must be recognized by the
      pediatricians and cardiologists since the disease can be identified by Tandem
      Mass Spectrometry; therefore, it should be considered to be included in expanded
      newborn screening program, allowing early diagnosis and intervention in order to
      ensure better outcome and prevent complications. 

PMID- 24044065
TI  - Urolithiasis in an adult with primary obstructive megaureter: a case report.
AB  - This is a rare case of adult primary obstructive megaureter complicated by
      combined uric acid-oxalate lithiasis of the ureter and renal stones. A 24-year
      old male patient presented with frank hematuria on exercise of 4 years duration.
      The patient had an open surgery in the form of excision of stenotic segment of
      ureter and left ureteric re-implantation with removal of ureteric and renal
      stones. Congenital megaureter is a diagnosis that urologists and radiologists
      need to consider in the setting of isolated distal ureteral dilation, as the
      diagnosis of adult megaureter may require more involved surgical measures to
      prevent recurrence of adverse symptoms. 

PMID- 24044066
TI  - Nutritional practices of athletes in oman: a descriptive study.
AB  - OBJECTIVE: Adequate dietary intake is crucial for optimum training and
      performance of athletes. There is almost no available information related to
      dietary practices among Omani athletes, especially during the competition. This
      study aimed to assess the nutritional practices (nutritional knowledge, eating
      habits and daily nutrients intake) among Omani male handball athletes in Muscat
      city, Oman. METHODS: This is a cross sectional study including 35 male handball
      athletes involved in serious training for no less than three years. Data
      collection was done through personal interviews using a study questionnaire which
      enlisted questions relating to socio-demographic information, anthropometric
      measurements and nutritional practices. All the study participants declared no
      intake of anabolic steroids. RESULTS: The mean age of the study participants was
      27 +/- 3 years. Their anthropometric assessment revealed that their mean height
      was 166 +/- 12 cm, mean weight was 75 +/- 10 kg, and body mass index was 27 +/-
      3. Nutritional knowledge analysis revealed that 80% had no nutritional
      supervision by a nutritionist/dietitian. Their knowledge of nutritional
      requirements was only 23% correct for total energy intake, 63% for protein
      intake, 46% for carbohydrate intake, 11% for fat intake and 83% for water intake.
      Eating habits indicated that 55% had <3 meals/day, 51% had lunch as the principal
      meal, 51% always added extra salt to their food, 28% took protein supplements on
      a daily basis, and 51% used pre-competition glycogen load diet. However, none
      consumed vitamins or mineral supplements. The mean daily caloric intake was 3674
      +/- 265 kcal/day, which was roughly comprised of 596 +/- 66 g carbohydrates, 147
      +/- 28 g of protein and 78 +/- 20 g of total fat. CONCLUSION: Professional
      nutritional supervision is needed in order to improve the nutritional knowledge
      and eating habits of Omani athletes, and therefore improve their athletic
      performance.

PMID- 24044067
TI  - Clinical and Demographic Profile of Attendees at Baghdad's Walk-in Psychiatric
      Clinic.
AB  - OBJECTIVE: Few studies have examined clinical and demographic profile of
      attendees of a walk-in psychiatric clinic in countries ravaged by wars. The aim
      of this study is to quantify the characteristics of attendees of an open walk-in
      psychiatric clinic in a general hospital in Baghdad and the suburb towns of Iraq
      in the year 2010. METHODS: As part of a retrospective survey, information on
      specific variables (socio-demographic background, clinical characteristics and
      attendance rate) were sought from medical records in the year 2010 (January to
      December). RESULTS: Despite the shortcomings expected from a country coming out
      of the ravage of war, the survey included 2,979 attendees (1,864 [63%] males and
      1,115 [37%] females) of a walk-in psychiatric clinic who fulfilled the inclusion
      criteria. The profile of attendees indicated that a majority of the cohort was
      self-referred with a predominance of employed males, aged 19 to 49 years,
      residing in Baghdad City. Depression and psychosis were the most common diagnosis
      given. CONCLUSION: The observed patterns are discussed within the available
      literature relevant to consultation liaison psychiatry, and specific to
      situations in Iraq and Arab/Islamic cultural patterning.

PMID- 24044068
TI  - An uncommon cause of headache.

PMID- 24044069
TI  - Intraoperative assessment of coronary artery bypass graft patency.

PMID- 24044070
TI  - Prevalence of celiac disease in omani children with type 1 diabetes mellitus: a
      cross sectional study.

PMID- 24044071
TI  - Validation of the French version of the Pittsburgh Sleep Quality Index Addendum
      for posttraumatic stress disorder.
AB  - BACKGROUND: Sleep disturbances are one of the main complaints of patients with
      trauma-related disorders. The original Pittsburgh Sleep Quality Index Addendum
      for PTSD (PSQI-A) is self-report instrument developed to evaluate posttraumatic
      stress disorder (PTSD)-specific sleep disturbances in trauma-exposed individuals.
      However, to date, the PSQI-A has not yet been translated nor validated in French.
      OBJECTIVE: THE PRESENT STUDY AIMS TO: a) translate the PSQI-A into French, and b)
      examine its psychometric properties. METHOD: Seventy-three adult patients (mean
      age=40.3 [SD=15.0], 75% females) evaluated in a specialized psychotraumatology
      unit completed the French versions of the PSQI-A, Pittsburgh Sleep Quality Index
      (PSQI), Hospital Anxiety and Depression Scale (HADS), and Impact Event Scale
      Revised (IES-R). RESULTS: The French version of the PSQI-A showed satisfactory
      internal consistency, inter-item correlations, item correlations with the total
      score, convergent validity with PTSD and anxiety measures, and divergent validity
      with a depression measure. CONCLUSION: Our findings support the use of the French
      version of the PSQI-A for both clinical care and research. The French version of
      the PSQI-A is an important addition to the currently available instruments that
      can be used to examine trauma-related sleep disturbances among French-speaking
      individuals.

PMID- 24044072
TI  - Neuroprotective effects of quetiapine on neuronal apoptosis following
      experimental transient focal cerebral ischemia in rats.
AB  - OBJECTIVE: This study was undertaken in the belief that the atypical
      antipsychotic drug quetiapine could prevent apoptosis in the penumbra region
      following ischemia, taking into account findings that show 5-hydroxytryptamine-2
      receptor blockers can prevent apoptosis. METHODS: We created 5 groups, each
      containing 6 animals. Nothing was done on the K-I group used for comparisons with
      the other groups to make sure adequate ischemia had been achieved. The K-II group
      was sacrificed on the 1st day after transient focal cerebral ischemia and the K
      III group on the 3rd day. The D-I group was administered quetiapine following
      ischemia and sacrificed on the 1st day while the D-II group was administered
      quetiapine every day following the ischemia and sacrificed on the 3rd day. The
      samples were stained with the immunochemical TUNEL method and the number of
      apoptotic cells were counted. RESULTS: There was a significant difference between
      the first and third day control groups (K-II/K-III : p=0.004) and this indicates
      that apoptotic cell death increases with time. This increase was not encountered
      in the drug groups (D-I/D-II : p=1.00). Statistical analysis of
      immunohistochemical data revealed that quetiapine decreased the apoptotic cell
      death that normally increased with time. CONCLUSION: Quetiapine is already in
      clinical use and is a safe drug, in contrast to many substances that are used to
      prevent ischemia and are not normally used clinically. Our results and the
      literature data indicate that quetiapine could help both as a neuronal protector
      and to resolve neuropsychiatric problems caused by the ischemia in cerebral
      ischemia cases.

PMID- 24044073
TI  - Valproic Acid increases expression of neuronal stem/progenitor cell in spinal
      cord injury.
AB  - OBJECTIVE: This study investigates the effect of valproic acid (VPA) on
      expression of neural stem/progenitor cells (NSPCs) in a rat spinal cord injury
      (SCI) model. METHODS: Adult male rats (n=24) were randomly and blindly allocated
      into three groups. Laminectomy at T9 was performed in all three groups. In group
      1 (sham), only laminectomy was performed. In group 2 (SCI-VPA), the animals
      received a dose of 200 mg/kg of VPA. In group 3 (SCI-saline), animals received
      1.0 mL of the saline vehicle solution. A modified aneurysm clip with a closing
      force of 30 grams was applied extradurally around the spinal cord at T9, and then
      rapidly released with cord compression persisting for 2 minutes. The rats were
      sacrificed and the spinal cord were collected one week after SCI.
      Immunohistochemistry (IHC) and western blotting sample were obtained from 5 mm
      rostral region to the lesion and prepared. We analyzed the nestin
      immunoreactivity from the white matter of ventral cord and the ependyma of
      central canal. Nestin and SOX2 were used for markers for NSPCs and analyzed by
      IHC and western blotting, respectively. RESULTS: Nestin and SOX2 were expressed
      significantly in the SCI groups but not in the sham group. Comparing SCI groups,
      nestin and SOX2 expression were much stronger in SCI-VPA group than in SCI-saline
      group. CONCLUSION: Nestin and SOX2 as markers for NSPCs showed increased
      expression in SCI-VPA group in comparison with SCI-saline group. This result
      suggests VPA increases expression of spinal NSPCs in SCI.

PMID- 24044074
TI  - Measurement of Critical Structures around Paraclinoidal Area : A Cadaveric
      Morphometric Study.
AB  - OBJECTIVE: Although removal of the anterior clinoid process (ACP) is essential
      surgical technique, studies about quantitative measurements of the space
      broadening by the anterior clinoidectomy are rare. The purposes of this study are
      to investigate the dimension of the ACP, to quantify the improved exposure of the
      parasellar space after extradural anterior clinoidectomy and to measure the
      correlation of each structure around the paraclinoidal area. METHODS: Eleven
      formalin-fixed Korean adult cadaveric heads were used and frontotemporal
      craniotomies were done bilaterally. The length of C6 segment of the internal
      carotid artery on its lateral and medial side and optic nerve length were checked
      before and after anterior clinoidectomy. The basal width and height of the ACP
      were measured. The relationships among the paraclinoidal structures were
      assessed. The origin and projection of the ophthalmic artery (OA) were
      investigated. RESULTS: The mean values of intradural basal width and height of
      the ACP were 10.82 mm and 7.61 mm respectively. The mean length of the C6 lateral
      and medial side increased 49%. The mean length of optic nerve increased 97%. At
      the parasellar area, the lengths from the optic strut to the falciform liament,
      distal dural ring, origin of OA were 6.69 mm, 9.36 mm and 5.99 mm, respectively.
      The distance between CN III and IV was 11.06 mm. CONCLUSION: With the removal of
      ACP, exposure of the C6 segments and optic nerve can expand 49% and 97%,
      respectively. This technique should be among a surgeon's essential skills for
      treating lesions around the parasellar area.

PMID- 24044075
TI  - Thromboembolic Events Associated with Electrolytic Detachment of Guglielmi
      Detachable Coils and Target Coils : Comparison with Use of Diffusion-Weighted MR
      Imaging.
AB  - OBJECTIVE: The purpose of this study was to retrospectively evaluate and compare
      the incidence of diffusion-weighted image (DWI) lesions between the Guglielmi
      detachable coil (GDC) and the Target coil for treating unruptured intracranial
      aneurysm. METHODS: From 2010 to 2011, consecutive 222 patients with an
      intracranial aneurysm underwent coil embolization. Inclusion criterias were : 1)
      unruptured intracranial aneurysm, 2) one or more GDC or Target coils used with or
      without other coils, 3) DWI examination within 24 hours after coiling, and 4)
      coiling performed without a balloon or stent. RESULTS: Ninety patients (92 cases)
      met the inclusion criteria. DWI lesions were detected in 55 (61.1%) of 90
      patients. In the GDC group (n=44), DWI lesions were detected in 31 (70.5%). The
      average number of DWI lesions was 5.0+/-8.7 (mean+/-SD; range, 1-40) in aneurysm
      related territory. In the Target coil group (n=48), DWI lesions were detected in
      24 (50.0%). The number of DWI lesion was 2.1+/-5.4 (range, 1-32) in aneurysm
      related territory. There was no significant correlation between a number of coils
      and DWI lesions. No significant differences were also observed in the number of
      DWI lesions in each group. CONCLUSION: The GDC and Target coils, which have an
      electrolytic detachable system, showed no differences in the incidence of DWI
      lesion.

PMID- 24044076
TI  - Anatomic Consideration of the C1 Laminar Arch for Lateral Mass Screw Fixation via
      C1 Lateral Lamina : A Landmark between the Lateral and Posterior Lamina of the
      C1.
AB  - OBJECTIVE: To clarify the landmark for deciding the entry point for C1 lateral
      mass screws via the posterior arch by using 3-dimensional (3D) computed images.
      METHODS: Resnick insisted that the C1 posterior arch could be divided into pure
      posterior and lateral lamina (C1 pedicle). Authors studied where this transition
      point (TP) is located between the posterior lamina and the C1 pedicle and how it
      can be recognized. The 3D computed images of 86 cadaver C1s (M : F=45 : 41) were
      used in this study. RESULTS: The superior ridge of the C1 posterior arch had 2
      types of orientation. One was in the vertical direction in the C1 posterior
      lamina and the other was in the horizontal direction in the C1 pedicle. The TP
      was located at the border between the 2 areas, the same site as the posterior end
      of the groove of the vertebral artery. On posterior-anterior projection, the
      posterior arch was sharpened abruptly at TP. We were unable to identify the TP in
      6.4% of specimens due to complete or partial osseous bridges. A total of 93.8% of
      the TP were located between the most enlarged point of the spinal canal and the
      medial wall of the vertebral artery. CONCLUSION: The anatomic entry zone of C1
      lateral laminar screws was clarified and identified based on the TP by using
      preoperative 3D computed images.

PMID- 24044077
TI  - Usefulness of Three Dimensional Proset MR Images for Diagnosis of Symptomatic L5
      S1 Foraminal and Extraforaminal Stenosis.
AB  - OBJECTIVE: To suggest a new useful diagnostic technique, principles of the
      selective excitation technique-magnetic resonance images (Proset-MRI), and to
      know the precise radiologic findings that can prove symptomatic foraminal and
      extraforaminal stenosis at L5-S1. METHODS: Nineteen patients with symptomatic L5
      S1 stenosis were checked by Proset-MRI. Four patients were performed
      decompressive surgery and 15 patients were performed selective nerve root block
      (SNRB) at L5. The pain scale of patients was checked by Visual Analogue Scale
      (VAS) scores at the pre- and post-treatment state. RESULTS: Proset-MRI findings
      of patients with symptomatic stenosis are root swelling (RS) and indentation. The
      comparisons with VAS scores had a meaningful statistical result at each RS
      (p<0.01) and indentation (p<0.01). However, the findings of RS combined with
      indentation lacked statistical significance (p=0.0249). In addition, according to
      a comparison with the treatment modalities, reducing of VAS scores had
      statistical meaningful significance in decompressive surgery cases (p<0.01), and
      also in SNRB cases (p<0.01) after a 3-month follow-up period. CONCLUSION: The
      three dimensional Proset-MRI is very useful and sensitive technique to diagnose
      the symptomatic foraminal and extraforaminal stenosis at L5-S1.

PMID- 24044078
TI  - Modic degenerative marrow changes in the thoracic spine : a single center
      experience.
AB  - OBJECTIVE: The purposes of this study were to evaluate the prevalence, types, and
      locations of Modic changes (MCs) in the thoracic spine in a large number of
      subjects, and to investigate the relation between the distributions of MCs and
      disc herniations (DHs) in the thoracic spine. METHODS: Two experienced
      musculoskeletal radiologists assessed the presence of MCs and DHs by consensus in
      the thoracic MRIs of 144 patients with non-specific back pain. Patient ages
      ranged from 22 to 88 years (mean=53.3+/-14.66 years), and 72 were female (50%).
      The prevalence, distribution, relation of MCs and DHs was recorded. RESULTS: MC
      was observed in 8 of the 144 patients (5.6%) and 10 of 1728 segments (0.58%). The
      most common MC was type II. Of the 8 patients exhibiting MC, 6 had type II
      (75.0%), and 2 had mixed MCs (type I/II or type II/III). MCs were distributed
      mainly at the mid-thoracic level (from T5/6 to T9/10). DH was detected in 18
      patients (12.5%), 36 of 1728 segments (2.1%). Of the 10 segments exhibiting MC, 5
      had DHs at the same level (50.0%). Accordingly, DH was strongly associated with
      MC (p=0.000). CONCLUSION: A low prevalence of MC was observed in the thoracic
      spine, and type II MC predominated. The low prevalence of MC in the thoracic
      spine suggests that it was caused by a relative lack of mobility as compared with
      the cervical and lumbar spines. And DHs were found to be strongly associated with
      MCs even in the thoracic spine.

PMID- 24044079
TI  - Multiple Densities of the Chronic Subdural Hematoma in CT Scans.
AB  - OBJECTIVE: Density of the chronic subdural hematoma (cSDH) is variable. It often
      appears to be mixed density. Multiple densities of cSDH may result from multiple
      episodes of trauma. We investigated the frequency of mixed density and the causes
      of head injuries representing each density. METHODS: We could collect 242 cases
      of chronic SDH. The cSDHs were classified into four groups; hypodensity,
      homogeneous isodensity, layered type, and mixed type on the basis of CT scans.
      RESULTS: The density of cSDH was isodense in 115 patients, hypodense in 31
      patients, mixed in 79 cases, and layered in 17 cases. The cSDH was on the left
      side in 115 patients, on the right side in 70 patients, and bilateral in 40
      patients. The history of trauma was identifiable in 122 patients. The etiology
      could be identified in 67.7% of the hypodense hematomas, while it was obscure in
      59.5% of the mixed hematomas. CONCLUSION: Mixed density of cSDH results from
      multiple episodes of trauma, usually in the aged. It is hard to remember all the
      trivial traumas for the patients with the mixed density cSDHs. Although there
      were membranes within the mixed density hematomas, burr-holes were usually enough
      to drain the hematomas.

PMID- 24044080
TI  - Evaluation of probability of survival using trauma and injury severity score
      method in severe neurotrauma patients.
AB  - OBJECTIVE: Despite several limitations, the Trauma Injury Severity Score (TRISS)
      is normally used to evaluate trauma systems. The aim of this study was to
      evaluate the preventable trauma death rate using the TRISS method in severe
      trauma patients with traumatic brain injury using our emergency department data.
      METHODS: The use of the TRISS formula has been suggested to consider definitively
      preventable death (DP); the deaths occurred with a probability of survival (Ps)
      higher than 0.50 and possible preventable death (PP); the deaths occurred with a
      Ps between 0.50 and 0.25. Deaths in patients with a calculated Ps of less than
      0.25 is considered as no-preventable death (NP). A retrospective case review of
      deaths attributed to mechanical trauma occurring between January 1, 2011 and
      December 31, 2011 was conducted. RESULTS: A total of 565 consecutive severe
      trauma patients with ISS>15 or Revised Trauma Score<7 were admitted in our
      institute. We excluded a total of 24 patients from our analysis : 22 patients
      younger than 15 years, and 2 patients with burned injury. Of these, 221 patients
      with head injury were analyzed in the final study. One hundred eighty-two
      patients were in DP, 13 in PP and 24 in NP. The calculated predicted mortality
      rates were 11.13%, 59.04%, and 90.09%. The actual mortality rates were 12.64%,
      61.547%, and 91.67%, respectively. CONCLUSION: Although it needs to make some
      improvements, the present study showed that TRISS performed well in predicting
      survival of traumatic brain injured patients. Also, TRISS is relatively exact and
      acceptable compared with actual data, as a simple and time-saving method.

PMID- 24044081
TI  - Isolated lateral sinus thrombosis presenting as cerebellar infarction in a
      patient with iron deficiency anemia.
AB  - As a rare cerebrovascular disease, cerebral venous thrombosis (CVT) is caused by
      various conditions including trauma, infection, oral contraceptive, cancer and
      hematologic disorders. However, iron deficiency anemia is not a common cause for
      CVT in adult. Posterior fossa infarction following CVT is not well demonstrated
      because posterior fossa has abundant collateral vessels. Here, we report a case
      of a 55-year-old man who was admitted with complaints of headache, nausea, and
      mild dizziness. The patient was diagnosed with isolated lateral sinus thrombosis
      presenting as cerebellar infarction. Laboratory findings revealed normocytic
      normochromic anemia due to iron deficiency, and the patient's symptoms were
      improved after iron supplementation. 

PMID- 24044082
TI  - Solitary ruptured aneurysm of the spinal artery of adamkiewicz with subarachnoid
      hemorrhage.
AB  - Spinal subarachnoid hemorrhage (SAH) due to solitary spinal aneurysm is extremely
      rare. A 45-year-old female patient visited the emergency department with severe
      headache and back pain. Imaging studies showed cerebral SAH in parietal lobe and
      spinal SAH in thoracolumbar level. Spinal angiography revealed a small pearl and
      string-like aneurysm of the Adamkiewicz artery at the T12 level. One month after
      onset, her back pain aggravated, and follow-up imaging study showed
      arachnoiditis. Two months after onset, her symptoms improved, and follow-up
      imaging study showed resolution of SAH. The present case of spinal SAH due to
      rupture of dissecting aneurysm of the Adamkiewicz artery underwent subsequent
      spontaneous resolution, indicating that the wait-and-see strategy may provide
      adequate treatment option. 

PMID- 24044083
TI  - Primary eosinophilic granuloma of adult cervical spine presenting as a
      radiculomyelopathy.
AB  - We report a case of 29-year-old man diagnosed as a primary eosinophilic granuloma
      (EG) lesion of the seventh cervical vertebra. He had paresthesia on both arms,
      and grasping weakness for 10 days. Cervical magnetic resonance image (MRI) showed
      an enhancing mass with ventral epidural bulging and cord compression on the
      seventh cervical vertebra. Additionally, we performed spine series MRI, bone scan
      and positive emission tomography for confirmation of other bone lesions. These
      studies showed no other pathological lesions. He underwent anterior cervical
      corpectomy of the seventh cervical vertebra and plate fixation with iliac bone
      graft. After surgical management, neurological symptoms were much improved.
      Histopathologic evaluation confirmed the diagnosis of EG. There was no evidence
      of tumor recurrence at 12 months postoperative cervical MRI follow-up. We
      reported symptomatic primary EG of cervical spine successfully treated with
      surgical resection. 

PMID- 24044085
TI  - Disseminated tuberculosis of central nervous system : spinal intramedullary and
      intracranial tuberculomas.
AB  - As a cause of spinal cord compression, intramedullary spinal tuberculoma with
      central nervous system (CNS) involvement is rare. Aurthors report a 66-year-old
      female presented with multiple CNS tuberculomas including spinal intramedullary
      tuberculoma manifesting paraparesis and urinary dysfunction. We review the
      clinical menifestation and experiences of previous reported literature. 

PMID- 24044084
TI  - Spinal subarachnoid hematoma as a complication of an intramuscular stimulation :
      case report and a review of literatures.
AB  - Intramuscular stimulation (IMS) is widely used to treat myofascial pain syndrome.
      IMS is a safe procedure but several complications have been described. To our
      knowledge, spinal subarachnoid hematoma has never been reported as a complication
      of an IMS. The authors have experienced a case of spinal subarachnoid hematoma
      occurring after an IMS, which was tentatively diagnosed as intracranial
      subarachnoid hemorrhage because of severe headache. Patient was successfully
      treated with surgery. Here, we report our case with a review of literature. 

PMID- 24044086
TI  - Symptomatic epidural pneumorrhachis : a rare entity.
AB  - Pneumorrhachis, which involves the entrapment of air or gas within the spinal
      canal, is a rare clinical entity, and the pathogenesis and etiologies of this
      uncommon entity are various and can present a diagnostic challenge. Usually,
      pneumorrhachis represents an asymptomatic epiphenomenon but it can produce
      symptoms associated with its underlying pathology. Here, we report a rare case of
      symptomatic epidural pneumorrhachis accompanying pneumothorax. Possible
      pathogenic mechanisms are discussed and a review of the literature is included. 

PMID- 24044087
TI  - Spontaneous spinal subdural hematoma concurrent with cranial subdural hematoma.
AB  - A 39-year old female presented with chronic spinal subdural hematoma manifesting
      as low back pain and radiating pain from both legs. Magnetic resonance imaging
      (MRI) showed spinal subdural hematoma (SDH) extending from L4 to S2 leading to
      severe central spinal canal stenosis. One day after admission, she complained of
      nausea and severe headache. Computed tomography of the brain revealed chronic SDH
      associated with midline shift. Intracranial chronic SDH was evacuated through two
      burr holes. Back pain and radiating leg pain derived from the spinal SDH
      diminished about 2 weeks after admission and spinal SDH was completely resolved
      on MRI obtained 3 months after onset. Physicians should be aware of such a
      condition and check the possibility of concurrent cranial SDH in patients with
      spinal SDH, especially with non-traumatic origin. 

PMID- 24044088
TI  - Current management of urethral stricture.
AB  - The surgical treatment of urethral stricture diseases is continually evolving.
      Although various surgical techniques are available for the treatment of anterior
      urethral stricture, no one technique has been identified as the method of choice.
      This article provides a brief updated review of the surgical options for the
      management of different sites and different types of anterior urethral stricture.
      This review also covers present controversies in urethral reconstruction. Among
      the various procedures available for treating urethral stricture, one-stage
      buccal mucosal graft urethroplasty is currently widely used. The choice of
      technique for urethroplasty for an individual case largely depends on the
      expertise of the surgeon. Therefore, urologists working in this field should keep
      themselves updated on the numerous surgical techniques to deal with any condition
      of the urethra that might surface at the time of surgery. 

PMID- 24044089
TI  - Technical aspects of holmium laser enucleation of the prostate for benign
      prostatic hyperplasia.
AB  - Holmium laser enucleation of the prostate (HoLEP) is a minimally invasive
      procedure and a size-independent treatment for benign prostatic hyperplasia with
      excellent long-term surgical outcome. HoLEP has become an alternative to
      conventional transurethral resection of the prostate or open prostatectomy owing
      to its efficacy and safety. Although HoLEP is known to have a steep learning
      curve, very few articles have addressed the technical aspects of HoLEP. Herein,
      we described detailed techniques and tips for HoLEP as performed at Seoul
      National University Hospital in a step-by-step manner with extensive review of
      the literature. 

PMID- 24044090
TI  - Percutaneous radiofrequency ablation of renal tumors: a single-center experience.
AB  - PURPOSE: To evaluate the oncological outcomes, complications, and changes in
      renal function in patients treated with computed tomography-guided percutaneous
      radiofrequency ablation (RFA) for small renal tumors. MATERIALS AND METHODS: The
      charts of patients who underwent RFA from 2006 to 2011 at a single institution
      were reviewed. Oncological and functional outcomes were assessed. Statistical
      analyses were performed with IBM SPSS ver. 18.0 (IBM Co., Armonk, NY, USA).
      RESULTS: A total of 44 RFAs were done in 40 patients. Biopsy prior to RFA was
      performed in 79.6% of procedures. Of those, 68.6% had renal cell carcinoma (RCC).
      Mean tumor diameter was 26.2 mm. Grade I complications occurred in 25% of cases
      (n=11, pain or elevated temperature) and grade II complications in 2.3% (n=1,
      perirenal bleeding needing two units of blood transfusion). Serum creatinine
      slightly increased by 0.14 mg/dL at 2 years after RFA (p<0.004). Tumor
      recurrences were suspected in 8 of 43 cases during follow-up. In five patients,
      the suspected recurrence was a false-positive as shown by a negative biopsy
      result or lack of contrast enhancement on subsequent imaging. The verified
      recurrence rate was 7.7% in all tumors and 2.5% in RCC at a mean follow-up of 2
      years. Tumor-free survival was 90% in all patients and 87.5% in those with RCC.
      Metastasis-free survival was 97.5% and cancer-specific survival was 100%.
      CONCLUSIONS: Percutaneous computed tomography-guided RFA shows promising results
      at intermediate follow-up. Suspected tumor recurrences are frequently false
      positives findings. A longer follow-up is required to verify the durability of
      these results.

PMID- 24044091
TI  - Oncologic outcomes of patients with Gleason score 7 and tertiary Gleason pattern
      5 after radical prostatectomy.
AB  - PURPOSE: We evaluated oncologic outcomes following radical prostatectomy (RP) in
      patients with a Gleason score (GS) of 7 with tertiary Gleason pattern 5 (TGP5).
      MATERIALS AND METHODS: We retrospectively reviewed the medical records of 310
      patients who underwent RP from 2005 to 2010. Twenty-four patients who received
      neoadjuvant or adjuvant antiandrogen deprivation or radiation therapy were
      excluded. Just 239 (GS 6 to 8) of the remaining 286 patients were included in the
      study. Patients were classified into four groups: GS 6, GS 7 without TGP5, GS 7
      with TGP5, and GS 8. We analyzed preoperative clinical factors, postoperative
      pathological outcomes, and biochemical recurrence (BCR). RESULTS: TGP5 in GS 7
      was an independent predictor of primary Gleason pattern 4, tumor volume larger
      than 10%, positive surgical margin, and lymphovascular invasion. The presence of
      TGP5 in GS 7 was not associated with BCR-free survival. Subgroup analyses
      revealed that BCR-free survival did not differ significantly between patients
      with GS 7 with TGP5 and those with GS 8 (p=0.120). In addition, time to BCR in
      patients with a higher percentage of TGP5 was shorter than that in patients with
      a lower percentage of TGP5. TGP5 in GS 7 was not a significant predictive factor
      for BCR, whereas prostate-specific antigen density and a positive surgical margin
      were shown to be independent predictors of BCR. CONCLUSIONS: TGP5 in GS 7 was an
      independent predictor of unfavorable pathologic outcomes. The rate of BCR was
      similar in GS 7 disease with TGP5 and in GS 8 disease, even though TGP5 was not a
      significant predictive factor for BCR in Cox proportional hazards models.

PMID- 24044092
TI  - Hospitalization decreases serum prostate-specific antigen values compared with
      outpatient values in patients with benign prostatic diseases.
AB  - PURPOSE: To investigate whether hospitalization influences serum prostate
      specific antigen (PSA) values. MATERIALS AND METHODS: Transrectal ultrasound
      guided prostate biopsies were performed for detecting prostate cancer in 2,017
      patients between February 2001 and April 2011 at Ajou University Hospital. Of
      those patients, 416 patients who were hospitalized for prostate biopsies, whose
      serum PSA values were measured at the outpatient department within 1 month of
      admission and also just after admission, and who had negative prostate biopsy
      results were included in the present study. We retrospectively reviewed the data
      of the 416 patients and compared the serum PSA values measured in the outpatient
      department with those measured during hospitalization. RESULTS: Among all 416
      patients, the interval between the two PSA measurements was 22.2 days (range, 3
      to 30 days) and the prostate size measured by transrectal ultrasonography was
      53.63 mL (range, 12.8 to 197.9 mL). Among all patients, mean serum PSA levels
      measured during hospitalization were significantly lower than those measured in
      the outpatient department (6.69 ng/mL vs. 8.01 ng/mL, p<0.001). When stratified
      according to age, the presence or absence of chronic prostatitis in the biopsy
      pathology, serum PSA levels, and prostate size, the serum PSA levels measured
      during hospitalization were significantly lower than those measured in the
      outpatient department in all subgroups, except in cases aged 20 to 39 years and
      those with PSA <4 ng/mL, in whom no significant differences were shown.
      CONCLUSIONS: Hospitalization decreases serum PSA values compared with those
      measured on an outpatient basis in patients with benign prostatic diseases.
      Therefore, serum PSA values should be checked on an outpatient basis for serial
      monitoring.

PMID- 24044093
TI  - Comparison of continence recovery between robot-assisted laparoscopic
      prostatectomy and open radical retropubic prostatectomy: a single surgeon
      experience.
AB  - PURPOSE: To evaluate the recovery of continence after robot-assisted laparoscopic
      prostatectomy (RALP) and open radical retropubic prostatectomy (RRP). MATERIALS
      AND METHODS: We identified 258 patients who underwent surgery by a single surgeon
      to treat localized prostate cancer. The patients were divided into two groups
      according to operative method. In group 1, 146 consecutive patients underwent
      RALP, and in group 2, 112 patients underwent RRP. To compare the interval until
      the return of urinary continence between the two groups, we used the Kaplan-Meier
      method and the log-rank test and Cox proportional hazard regression analyses.
      RESULTS: Differences between the two groups were found in mean estimated blood
      loss (EBL; p<0.001) and the rate of nerve sparing (p=0.004). When continence was
      defined as the use of 0 to 1 pad per day, 100% of group 1 and 98.2% of group 2
      reported continence at 12 months (p=0.189). When continence was defined as no pad
      use, however, there was a significant difference between the two groups at 12
      months: group 1, 95.7%, and group 2, 70.7% (p<0.001). The factors affecting time
      until no pad use in the univariate analysis with a Cox proportional hazards model
      were operation method, age, neurovascular bundle saving, membranous urethral
      length (MUL), EBL, and apical shape. In the multivariate analysis, only operation
      method, age, and MUL retained significance. CONCLUSIONS: Our study suggests that
      RALP is an independent factor for the recovery of continence and that RALP has
      advantages for postoperative continence recovery and the quality of continence
      compared with RRP.

PMID- 24044094
TI  - Comparison of laparoscopic radiofrequency ablation and open partial nephrectomy
      in patients with a small renal mass.
AB  - PURPOSE: We have performed both open partial nephrectomy (OPN) and laparoscopic
      radiofrequency ablation (RFA) on selected patients since January 2007 and have
      been following these patients through serial laboratory assessments and computed
      tomography (CT). The purpose of the present study was to evaluate long-term
      oncologic outcomes and renal function status for laparoscopic RFA versus OPN at a
      minimum follow-up of 3 years. MATERIALS AND METHODS: A total of 55 patients with
      exophytic, single small renal masses were treated with either OPN (n=14) or
      laparoscopic RFA (n=41) by a single surgeon. The indications for laparoscopic RFA
      were as follows: 1) cases with the greatest dimension of the renal mass <3 cm,
      and 2) cases in which the collecting system, renal calyx, and great vessels were
      free from the tumor margins by 1 cm. RESULTS: The estimated blood loss (EBL), the
      operation time, and the mean number of hospital days was significantly lower in
      the laparoscopic RFA group than in the OPN group. Oncologic data did not differ
      significantly between the two groups. Creatine clearance levels did not differ
      significantly compared with those before the operation in either group.
      CONCLUSIONS: Our data suggest excellent therapeutic outcomes with laparoscopic
      RFA with achievement of effective operative times, hospital stays, and EBL
      compared with OPN. According to our indications for laparoscopic RFA,
      laparoscopic RFA is an effective minimally invasive therapy for the treatment of
      small renal masses, yielding oncologic outcomes and renal function equivalent to
      those of OPN.

PMID- 24044095
TI  - Prostate-specific antigen mass and free prostate-specific antigen mass for
      predicting the prostate volume of korean men with biopsy-proven benign prostatic
      hyperplasia.
AB  - PURPOSE: It has been reported that prostate-specific antigen (PSA) correlates
      with prostate volume. Recently, some studies have reported that PSA mass (PSA
      adjusted for plasma volume) is more accurate than PSA at predicting prostate
      volume. In this study, we analyzed the accuracy of PSA and the related parameters
      of PSA mass, free PSA (fPSA), and fPSA mass in predicting prostate volume.
      MATERIALS AND METHODS: We retrospectively investigated 658 patients who underwent
      prostate biopsy from 2006 to 2012 and had a confirmed negative biopsy result.
      International Prostate Symptom Score (IPSS) questionnaire, PSA, fPSA, and
      prostate volume were investigated. PSA mass and fPSA mass were calculated by use
      of established formulas. The association between PSA-related parameters and IPSS
      and prostate volume was assessed by using Pearson correlation coefficient and
      receiver operating characteristic curves. RESULTS: There was no significant
      difference between PSA and PSA mass, fPSA, or fPSA mass in predicting prostate
      volume except in obese patients (p-value of PSA-PSA mass for 40 cm(3), 0.54; p
      value of fPSA-fPSA mass for 40 cm(3), 0.34). fPSA performed significantly better
      than PSA at predicting prostate volume (p-value for 40 cm(3), <0.001). IPSS and
      the aforementioned PSA-related parameters were not significantly correlated.
      CONCLUSIONS: PSA mass was not a better predictive value than PSA for estimating
      the prostate volume in Korean men except in obese men. This finding was also
      applicable to the relationship of fPSA and fPSA mass, which appeared to be more
      accurate predictors of prostate volume than either PSA or PSA mass.

PMID- 24044096
TI  - Relationship Between Spontaneous Passage Rates of Ureteral Stones Less Than 8 mm
      and Serum C-Reactive Protein Levels and Neutrophil Percentages.
AB  - PURPOSE: A ureter obstruction caused by a ureteral stone results in inflammatory
      changes in the proximal submucosal layer and prevents the spontaneous passage of
      the ureteral stone. Accordingly, we analyzed the relationship between the
      spontaneous passage rates of ureteral stones less than 8 mm in size and serum C
      reactive protein (CRP) levels and neutrophil percentages. MATERIALS AND METHODS:
      A total of 187 patients who were diagnosed with ureteral stones less than 8 mm in
      size and were managed consecutively at Keimyung University Dongsan Medical Center
      from January 2001 to January 2011 were retrospectively analyzed. Ureteral stone
      removal was defined as no ureteral stone shown in an imaging test without any
      treatment for 8 weeks after diagnosis. The patients were divided into three
      groups according to the levels of serum CRP and into two groups according to
      neutrophil percentage. The associations between these factors and ureteral stone
      passage rates were then examined. RESULTS: The ureteral stone passage rates of
      the low serum CRP level group, the medium serum CRP level group, and the high
      serum CRP level group were 94.1% (159/169), 70% (7/10), and 50.0% (4/8),
      respectively. The passage rates of ureteral stones in the group with a normal
      neutrophil percentage and in the group with a higher neutrophil percentage were
      94.5% (121/128) and 83.1% (49/59), respectively (p=0.011). CONCLUSIONS: Measuring
      serum CRP levels and neutrophil percentages in patients with small ureteral
      stones of less than 8 mm is useful in predicting whether the stone will be
      spontaneously passed. When the serum CRP level and neutrophil percentage of a
      patient are high, aggressive treatment such as extracorporeal shock wave
      lithotripsy should be considered.

PMID- 24044097
TI  - Serum total testosterone level and identification of late-onset hypogonadism: a
      community-based study.
AB  - PURPOSE: Late-onset hypogonadism (LOH) in aging males is a clinical and
      biochemical syndrome characterized by a decline in serum testosterone levels. LOH
      results in various physical and mental disabilities. We evaluated the
      relationship between serum testosterone levels and symptoms of LOH. MATERIALS AND
      METHODS: During an andropause screening program, we examined responses to the
      Saint Louis university androgen deficiency in aging males (ADAM) questionnaire
      and results on the International Index of Erectile Function (IIEF-5) in terms of
      clinical symptoms and evaluated serum total testosterone levels for a biochemical
      diagnosis of LOH in healthy community-living volunteers aged over 40 years.
      RESULTS: The mean age of the 534 men was 59.1 years (range, 40 to 79 years), and
      their mean serum testosterone level was 464.1+/-171.9 ng/dL. The serum
      testosterone level decreased significantly with age. There was a 92.5% positive
      response rate to the ADAM questionnaire. The percentage of patients whose serum
      testosterone level was <350 ng/dL among those with a positive response to the
      ADAM questionnaire was 25.6% (137 patients). The mean serum testosterone level
      among patients with a positive or negative ADAM questionnaire was 472.4+/-198.5
      ng/dL and 487.3+/-165.7 ng/dL, respectively (p>0.05). There was no significant
      correlation between IIEF-5 scores and serum testosterone levels. CONCLUSIONS:
      Among men over 40 years of age, 25.6% met the clinical and biochemical diagnostic
      criteria for LOH. There was no relationship between serum testosterone levels and
      symptoms of LOH.

PMID- 24044098
TI  - Effect of topical steroid (0.05% clobetasol propionate) treatment in children
      with severe phimosis.
AB  - PURPOSE: We report our experience with the use of a topical steroid, 0.05%
      clobetasol propionate, for the treatment of phimosis with clinical complications.
      MATERIALS AND METHODS: This was a retrospective analysis of the clinical outcomes
      of all patients presenting with phimosis to a single institution during the time
      period from October 2008 to May 2012. A total of 88 patients who had a Kikiros
      retractability grade of 4 or 5 and phimosis-associated clinical complications,
      such as ballooning of the prepuce, balanoposthitis, or a history of urinary tract
      infection (UTI), were instructed to apply 0.05% clobetasol propionate cream to
      the slightly retracted foreskin and to massage gently while retracting the
      foreskin. The efficacy of treatment was evaluated at 4 weeks from the initiation
      of therapy. RESULTS: A total of 60 of the 88 patients (68.2%) showed a complete
      response (i.e., full retraction of the foreskin) to the therapy. The phimotic
      ring disappeared in 25 of the 88 patients (28.4%) after treatment. Patients who
      had a history of balanoposthitis, smegma, ballooning of the prepuce, or UTI
      showed significantly poorer improvement in preputial retraction (p<0.001,
      p<0.001, p<0.001, and p=0.02, respectively) and phimotic ring disappearance
      (p<0.001, p=0.001, p<0.001, and p=0.001, respectively) after treatment. No
      significant local or systemic side effects were associated with the
      administration of topical steroids. CONCLUSIONS: Topical application of 0.05%
      clobetasol propionate cream and skin stretching is a safe, simple, and effective
      procedure with no significant side effects for severe phimosis in prepubertal
      boys.

PMID- 24044099
TI  - Decreased DBC1 Expression Is Associated With Poor Prognosis in Patients With Non
      Muscle-Invasive Bladder Cancer.
AB  - PURPOSE: The deleted in bladder cancer 1 (DBC1) gene is located within chromosome
      9 (9q32-33), a chromosomal region that frequently shows loss of heterozygosity in
      bladder cancer (BC). It is suspected that it acts as a tumor suppressor gene, but
      its prognostic value remains unclear. The aim of the present study was to
      investigate the value of DBC1 as a prognostic marker in BC. MATERIALS AND
      METHODS: The expression of DBC1 was determined by real-time polymerase chain
      reaction analysis in 344 patients with BC (220 non-muscle-invasive BC [NMIBC] and
      124 muscle-invasive BC [MIBC]) and in 34 patients with normal bladder mucosa. The
      results were compared with clinicopathologic parameters, and the prognostic value
      of DBC1 was evaluated by Kaplan-Meier analysis and a multivariate Cox regression
      model. RESULTS: DBC1 expression was significantly decreased in patients with MIBC
      compared with those diagnosed with NMIBC (p=0.010). Patients with aggressive
      tumor characteristics had lower DBC1 expression levels in NMIBC (each, p<0.05).
      By multivariate Cox regression analysis, low DBC1 expression was a predictor of
      progression to MIBC (hazard ratio, 7.104; p=0.013). Kaplan-Meier estimates
      revealed a significant difference in tumor recurrence, progression to MIBC, and
      cancer-specific survival depending on the level of DBC1 expression in NMIBC (log
      rank test, each, p<0.05). CONCLUSIONS: The expression of DBC1 was associated with
      tumor aggressiveness, progression to MIBC, and survival in NMIBC. Our results
      suggest that DBC1 expression can be a useful prognostic marker for patients with
      NMIBC.

PMID- 24044100
TI  - Squamous cell carcinoma of the suprapubic cystostomy tract with bladder
      involvement.
AB  - Herein we report a case of a squamous cell carcinoma of a well-healed suprapubic
      cystostomy tract scar involving the bladder mucosa in a 56-year-old man. He
      presented with a spontaneous suprapubic urinary leak from a suprapubic cystostomy
      tract scar. He had a history of urethral stricture and failed urethroplasty.
      Preoperative cystoscopy suggested a bladder mass. Transurethral biopsy of the
      bladder mass revealed a squamous cell carcinoma confined to the suprapubic
      cystostomy tract involving the bladder mucosa. The patient died 6 months after
      the start of radiation therapy after lung metastasis and pneumonia. 

PMID- 24044101
TI  - Isolated renal mucormycosis in a healthy immunocompetent patient: atypical
      presentation and course.
AB  - Isolated renal mucormycosis is rarely identified and has been described in only a
      handful of cases. We hereby report a case of isolated renal mucormycosis with an
      atypical presentation in an immunocompetent patient with no identifiable risk
      factors. A 30-year-old nondiabetic male presented with a poorly functioning right
      kidney with minimal constitutional symptoms. The patient underwent a right simple
      nephrectomy. Histopathology revealed necrotizing xanthogranulomatous
      pyelonephritis with mucormycosis. The postoperative period was uneventful and the
      patient was managed without any antifungal administration. We hereby emphasize
      that renal mucormycosis can affect immunocompetent healthy adults without any
      previously known risk factors and that asymptomatic patients with no evidence of
      fungemia or disseminated disease can be managed without administration of
      intravenous amphotericin. 

PMID- 24044102
TI  - Highest Efficiency Two-Photon Degradable Copolymer for Remote Controlled Release.
AB  - To address the scarcity of polymers that degrade upon absorption of near infrared
      (NIR) light, we introduce a new polymer containing moieties in its backbone
      capable of highly efficient NIR-triggered photocleavage. The polymer rapidly
      undergoes backbone scission in response to both UV-Vis and near infrared light
      via two-photon absorption, as revealed by gel permeation chromatography. Cleavage
      of photosensitive groups from the backbone is confirmed by 1H NMR. These polymers
      were successfully formulated into particles encapsulating a dye that was released
      upon irradiation with UV-Vis and NIR light, as indicated by changes in
      fluorescence characteristic of increased solvent interaction with cargo. Thus,
      this new polymer is readily photocleaved by UV-Vis and NIR light, giving it a
      variety of potential applications in photopatterning and on-demand release.

PMID- 24044103
TI  - Block copolymers containing a hydrophobic domain of membrane-lytic peptides form
      micellar structures and are effective gene delivery agents.
AB  - Endosomal release peptides have been incorporated in synthetic gene delivery
      formulations to increase transfection efficiencies. In this work, cationic
      copolymers containing sHGP, a membrane-lytic peptide derived from HIV gp41, were
      synthesized and evaluated. Diblock, with sHGP displayed on one block, and
      statistical, with sHGP randomly displayed, copolymers were prepared via RAFT
      polymerization. While the statistical copolymer existed as unimers in solution,
      amphiphilic diblock copolymers self-assembled into cationic micelles in aqueous
      solution as evidenced by TEM and dynamic light scattering analyses. This self
      assembly sequestered the lytic domain and significantly reduced the cytotoxicity
      of the materials. However, when complexed with plasmid DNA, both the diblock and
      statistical copolymers of sHGP showed higher gene delivery efficacy compared to
      the copolymers without the membrane lytic motif. The ability of amphiphilic,
      diblock copolymers containing endosomal release motifs to self-assemble and
      sequester lytic domains is a promising feature for the nucleic acid delivery.

PMID- 24044104
TI  - Nor-1, a novel incretin-responsive regulator of insulin genes and insulin
      secretion.
AB  - B-cell failure at the onset of type 2 diabetes is caused by a decline in beta
      cell function in the postprandial state and loss of pancreatic beta-cell mass.
      Recently, we showed an association between increased insulin secretion and a
      single nucleotide polymorphism (SNP), SNP rs12686676, in the NR4A3 gene locus
      encoding the nuclear receptor Nor-1. Nor-1 is expressed in beta-cells, however,
      not much is known about its function with regard to insulin gene expression and
      insulin secretion. Nor-1 is induced in a glucose-/incretin-dependent manner via
      the PKA pathway and directly induces insulin gene expression. Additionally, it
      stimulates insulin secretion possibly via regulation of potentially important
      genes in insulin exocytosis. Moreover, we show that the minor allele of NR4A3 SNP
      rs12686676 fully rescues incretin resistance provoked by a well-described
      polymorphism in TCF7L2. Thus, Nor-1 represents a promising new target for
      pharmacological intervention to fight diabetes. 

PMID- 24044105
TI  - Korean Society for Sexual Medicine and Andrology (KSSMA) Guideline on Erectile
      Dysfunction.
AB  - In February 2011, the Korean Society for Sexual Medicine and Andrology (KSSMA)
      realized the necessity of developing a guideline on erectile dysfunction (ED)
      appropriate for the local context, and established a committee for the
      development of a guideline on ED. As many international guidelines based on
      objective evidence are available, the committee decided to adapt these guidelines
      for local needs instead of developing a new guideline. Considering the extensive
      research activities on ED in Korea, data with a high level of evidence among
      those reported by Korean researchers have been collected and included in the
      guideline development process. The latest KSSMA guideline on ED has been
      developed for urologists. The KSSMA hopes that this guideline will help
      urologists in clinical practice. 

PMID- 24044106
TI  - Risks and benefits of late onset hypogonadism treatment: an expert opinion.
AB  - Late-onset hypogonadism (LOH) is a syndromic condition that has a well-recognized
      association with sexual and reproductive failure. LOH is frequently associated
      with chronic conditions including cardiovascular diseases (CVD), obesity,
      osteoporosis, HIV infection, renal failure, and obstructive pulmonary diseases.
      Despite this evidence, in patients with these conditions, LOH is still only
      rarely investigated and testosterone replacement therapy (TRT) rarely considered.
      In this paper, we critically reviewed the available evidence on LOH treatment
      focusing on possible risks and benefits. Medical therapy of LOH should be
      individualized depending on the etiology of the disease and the patient's
      expectations. The fear of prostate cancer and the risk of erythrocytosis probably
      represent the main limitations of TRT in aging men. However, TRT in healthy older
      men in near physiological doses does not appear to incur serious adverse events,
      although regular monitoring of prostate-specific antigen and hematocrit levels is
      required. Available evidence also suggests that TRT might ameliorate central
      obesity and glycometabolic control in patients with metabolic syndrome and type 2
      diabetes. In addition, TRT has been associated with an increase in bone mineral
      density in men with osteoporosis, with an improvement in lean body mass in
      subjects with human immunodeficiency virus infection or chronic obstructive
      pulmonary disease, as well as with peripheral oxygenation in patients with
      chronic kidney diseases. Despite this evidence, however, it should be recognized
      that the results of these trials were heterogeneous and limited by small sample
      sizes. Hence, further research is required regarding the long-term benefits and
      adverse effects of TRT in LOH. 

PMID- 24044107
TI  - The Relationship between Testosterone Deficiency and Men's Health.
AB  - Testosterone is important in the physiology of various organs and tissues. The
      serum testosterone concentration gradually declines as one of the processes of
      aging. Thus, the concept of late-onset hypogonadism has gained increasing
      attention in the last few years. Reported symptoms of late-onset hypogonadism are
      easily recognized and include diminished sexual desire and erectile quality,
      particularly in nocturnal erections, changes in mood with concomitant decreases
      in intellectual activity and spatial orientation, fatigue, depression and anger,
      a decrease in lean body mass with associated decreases in muscle volume and
      strength, a decrease in body hair and skin alterations, and decreased bone
      mineral density resulting in osteoporosis. Among these various symptoms, sexual
      dysfunction has been the most common and necessary to treat in the field of
      urology. It is well known that a low serum testosterone level is associated with
      erectile dysfunction and hypoactive sexual libido and that testosterone
      replacement treatment can improve these symptoms in patients with hypogonadism.
      Recently, in addition to sexual dysfunction, a close relationship between
      metabolic syndrome, characterized by central obesity, insulin resistance,
      dyslipidemia, and hypertension, and late-onset hypogonadism has been highlighted
      by several epidemiologic studies. Several randomized control trials have shown
      that testosterone replacement treatment significantly decreases insulin
      resistance in addition to its advantage for obesity. Furthermore, metabolic
      syndrome is one of the major risk factors for cardiovascular disease, and a low
      serum testosterone level is closely related to the development of
      atherosclerosis. Presently, it is speculated that a low serum testosterone level
      may increase the risk for cardiovascular disease. Thus, testosterone is a key
      molecule in men's health, especially that of elderly men. 

PMID- 24044108
TI  - The role of androgen in the adipose tissue of males.
AB  - Adipose tissue, where various metabolic hormones are secreted, plays a role in
      metabolizing different substances including androgen. Within fat tissue, enzymes
      such as aromatase and aldo-keto reductase 1C are responsible for metabolizing
      testosterone into estrogen and 5-dihydrotestosterone into inactive metabolites.
      Adipose tissue can also affect the secretion of gonadotropin, which influences
      the formation of androgen in the testes. At the same time, androgen has an impact
      on the distribution and proliferation of adipose tissue. The adrenoreceptors for
      catecholamines, which have been proven to play an essential role in controlling
      lipolysis, function by being up-regulated by androgens. Furthermore, androgens
      regulate the activity of lipoprotein lipase, a key enzyme involved in
      intracellular esterification of adipose tissue. 

PMID- 24044109
TI  - Effects of sesame oil on the reproductive parameters of diabetes mellitus-induced
      male rats.
AB  - PURPOSE: The purpose of the present study was to investigate the effect of sesame
      oil on the reproductive parameters of diabetic male Wistar rats. MATERIALS AND
      METHODS: The adult male rats in a split plot design were divided into normal
      (n=10), normal 5% (n=5; 5% sesame oil enriched diet), diabetic (Streptozocin
      induced diabetes; n=9), diabetic 5% (n=9; 5% sesame oil enriched diet), and
      diabetic 10% (n=9; 10% sesame oil enriched diet) groups. Diet supplementation
      continued for 56 days. RESULTS: Sesame oil supplementation did not reduce the
      plasma glucose concentration of rats in the diabetic groups (p>0.05). The total
      spermatogonia, spermatocytes, Leydig cells/tubule, and the germ cell to Sertoli
      cell ratio were lower in the diabetic rats than the normal ones (p<0.05), and
      with the exception of spermatogonia counts, these values improved by the addition
      of sesame oil to the diet (p<0.05). The sperm progressive motility and viability
      were lower in the diabetic rats (p<0.05) and sesame oil supplementation did not
      improve them. Incorporation of sesame oil into the diet improved the plasma
      testosterone concentration of the diabetic rats in a dose-dependent manner
      (p<0.05). CONCLUSIONS: In summary, sesame oil supplementation improved the
      reproductive parameters of diabetic rats at the levels of the testicular
      microstructure and function, but was not effective in protecting the epididymal
      sperm.

PMID- 24044110
TI  - The Anti-Inflammatory Effects of a New Herbal Formula (WSY-1075) in a
      Nonbacterial Prostatitis Rat Model.
AB  - PURPOSE: The aim of this study was to investigate the anti-inflammatory effects
      of a new herbal formula (WSY-1075) in a nonbacterial prostatitis rat model.
      MATERIALS AND METHODS: Prostatitis was induced in male Wistar rats (n=32) by
      treatment with 17 beta-estradiol and dihydrotestosterone for 4 weeks. After the
      induction of prostatitis, the rats were randomly divided into one of four
      treatment groups: control (n=8), ciprofloxacin (n=8), WSY-1075 (100 mg/kg) (n=8),
      and WSY-1075 (400 mg/kg) (n=8). After 4 weeks of treatment, the prostatic
      proinflammatory cytokine (tumor necrosis factor-alpha, interleukin [IL]-6, and IL
      8) levels and histological findings were noted. RESULTS: The ciprofloxacin and
      WSY-1075 treatment groups showed significantly decreased proinflammatory cytokine
      levels compared with the control group. Histologically, treatment with
      ciprofloxacin and WSY-1075 significantly suppressed the severity of prostatitis
      lesions compared with those in the control group. No differences in the
      proinflammatory cytokine levels or histologic findings were observed with the
      dose dependent treatment of WSY-1075. CONCLUSIONS: The new herbal formula, WSY
      1075, showed effective anti-inflammatory activities in the prostate and may be
      useful for the clinical treatment of nonbacterial prostatitis. Our findings
      suggest that WSY-1075 has a beneficial effect on the prevention and treatment of
      nonbacterial prostatitis.

PMID- 24044111
TI  - A Quality Analysis of Randomized Controlled Trials about Erectile Dysfunction.
AB  - PURPOSE: A low quality clinical trial could produce errors, and these errors
      could, in turn, distort the results of the clinical trial. To avoid applying
      distorted results of trials clinically, a quality analysis of clinical trials is
      needed. MATERIALS AND METHODS: We selected randomized controlled trials (RCTs)
      about erectile dysfunction (ED) conducted in Korea using Medline and KoreaMed.
      Quality assessment of selected RCTs was performed using three assessment tools
      (Jadad scales, van Tulder scale, Cochrane Collaboration Risk of Bias Tool
      [CCRBT]). RESULTS: The first RCT about ED conducted in Korea was published in
      2002. Since 2002, a total of 20 RCTs have been published in medical journals.
      Among the 20 articles, only 1 article was found to have a low risk of bias
      according to the CCRBT. On the Jadad scale, there were 17 high quality articles,
      while 19 articles were assessed as high quality by the VTS. Only 2 RCTs described
      the randomization method adequately. Only 1 RCT presented allocation concealment.
      CONCLUSIONS: A low quality clinical trial could produce errors, and these errors
      could, in turn, distort the results of the clinical trial. To avoid applying
      distorted results of trials clinically, a quality analysis of clinical trials is
      needed. The quality of RCTs was found to be high because almost all of the
      selected RCTs were double blinded studies. However, the quality of RCTs was
      inadequate with regard to the lack of randomization and absence of allocation
      concealment. Therefore, performing adequate randomization and adding a
      description of the appropriate concealment of allocation may improve the quality
      of RCTs.

PMID- 24044112
TI  - The surgical procedure is the most important factor affecting continence recovery
      after laparoscopic radical prostatectomy.
AB  - PURPOSE: We analyzed factors associated with early recovery of continence after
      laparoscopic radical prostatectomy. MATERIALS AND METHODS: Among 467 patients
      treated with laparoscopic radical prostatectomy for localized prostate cancer
      between 2007 and 2012, 249 patients who underwent a preoperative urodynamic study
      were enrolled. The patients' age, prostate volume, preoperative serum prostate
      specific antigen (PSA), Gleason score, pathologic stage, and preoperative
      urodynamic parameters were recorded. The preoperative membranous and prostatic
      urethral length on magnetic resonance image, nerve sparing technique, and type of
      surgical procedure (extrafascial and intrafascial) were analyzed. Patients were
      considered to have early recovery of continence when they needed no pad in 3
      months or less after surgery. RESULTS: Ninety-two patients were in the early
      recovery group and 157 were in the late recovery group. The membranous urethral
      lengths were 12.06+/-2.56 and 11.81+/-2.87 mm, and prostatic urethral lengths
      were 36.39+/-6.15 and 37.45+/-7.55 mm in each group, respectively. The membranous
      posterior urethral length ratios were 0.25+/-0.06 and 0.24+/-0.06, and prostatic
      posterior urethral length ratios were 0.75+/-0.06 and 0.76+/-0.06, respectively.
      In and of themselves, the membranous and prostatic urethral lengths were not
      associated with recovery duration however, the membranous-total and prostatic
      total urethral length ratios were related (p=0.024 and 0.024, respectively). None
      of the urodynamic parameters correlated with continence recovery time. In the
      multivariate analysis, the type of surgical procedure (odds ratio [OR], 7.032;
      95% confidence interval [CI], 2.660 to 18.590; p<0.001) and membranous urethral
      length (OR, 0.845; 95% CI, 0.766 to 0.931; p=0.001) were significantly related to
      early recovery of continence. CONCLUSIONS: The current intrafascial surgical
      procedure is the most important factor affecting early recovery of continence
      after laparoscopic radical prostatectomy.

PMID- 24044113
TI  - Testosterone deficiency with erectile dysfunction in mongolian men.
AB  - PURPOSE: To detect the testosterone deficiency syndrome in Mongolian men over 40
      years old with erectile dysfunction (ED). MATERIALS AND METHODS: Total of 309
      males over 40 years of age who received medical care at the ADAM Urology and
      Andrology Clinic from 2010 to 2011 were included in this study. An approval from
      the Ethics Committee of the Ministry of Health of Mongolia was obtained, and each
      study participant signed a consent form at the beginning of the study. The
      participants were assigned to either an ED group or a control group, depending on
      the results of the international index of erectile function (IIEF)-5
      questionnaire. The ED group was further divided into three groups (moderate,
      severe, and very severe) based on the level of ED. The total testosterone (TT)
      levels were determined in the blood serum using a competitive enzyme-linked
      immunesorbent assay (ELISA) analytical system UBI MagiwelTM Testosterone
      Quantitative test, and free testosterone (FT) calculated as described by the
      Vermeulen calculation. Test samples were collected between 8:00 and 11:00 am in
      the mornings and testosterone deficiency syndrome was diagnosed based on the
      International Society for the Study of the Aging Male guidelines, particularly,
      if TT was <=3.46 ng/ml or free testosterone FT was <=0.072 ng/ml. RESULTS: ED of
      moderate, severe, and very severe levels was diagnosed in 199 (64.41%) out of 309
      participants. There was an inverse relationship between the main IIEF-5 score and
      age (r=-0.380, p<0.01). The average TT was 5.75+/-2.316 ng/ml and FT was 0.091+/
      0.0084 ng/ml. Compared to the ED group, the control group had a higher TT level:
      5.6440+/-1.177 ng/ml and 5.812+/-2.316 ng/ml, respectively. In the control group,
      the FT level was 0.061+/-0.0084 ng/ml, whereas it was 0.041+/-0.0076 ng/ml in the
      ED group. CONCLUSIONS: Our study showed that most of the aging males who came to
      the clinic had moderate to very severe ED (64.55%). The levels of TT (5.644+/
      1.177 ng/ml) and FT (0.041+/-0.0036 ng/ml) were significantly lower in ED
      patients (p<0.05). The testosterone deficiency syndrome was detected in 24.27% of
      the ED group.

PMID- 24044114
TI  - Ectopic prostate tissue at the bladder dome presenting as a bladder tumor.
AB  - The presence of ectopic prostate tissue in the bladder is common, but the
      involvement of the bladder dome has rarely been reported. This case report
      describes a 72-year-old man who presented with gross painless hematuria.
      Cystoscopy revealed a smooth sessile mass at the dome region of the bladder. A
      complete transurethral resection of the mass was performed. Histopathological
      examination of the mass revealed the presence of benign ectopic prostatic tissue.

PMID- 24044115
TI  - Intrascrotal and extratesticular multiple schwannoma.
AB  - Schwannoma, which may occur in any region of the body, is very rare in the
      scrotum. Schwannomas are tumors that originate from Schwann cells and,
      theoretically, could affect any nerve. In spite of the rich innervation of the
      genital area, these kinds of tumors are not common in the scrotum. A 67-year-old
      man visited our hospital for investigation of a 2-year episode of multiple slowly
      growing masses in the scrotum. Testicular tumor markers were within normal range
      (beta human chorionic gonadotropin <5 mIU, alpha-fetoprotein : 4.86 ng/ml).
      Scrotal ultrasonography revealed intrascrotal and extratesticular masses in the
      mid-scrotal region. Complete excision of the scrotal masses was performed. After
      surgery there was no testicular invasion. Histological examination of the
      resected specimen showed them to be schwannomas of the scrotum. We report one
      case of multiple schwannomas of the scrotum with a review of the literature. 

PMID- 24044116
TI  - Author response.

PMID- 24044117
TI  - Reflections: neurology and the humanities. More than "Just the facts, ma'am".

PMID- 24044118
TI  - Response to letter regarding article, "hypothermia in comatose survivors from out
      of-hospital cardiac arrest: pilot trial comparing 2 levels of target
      temperature".

PMID- 24044119
TI  - Reply to Hrudey: Tracking the extent of oil sands airborne pollution.

PMID- 24044120
TI  - Reply to Klitz and Niklasson: Can viral infections explain the cross-sectional
      Austrian diabetes data?

PMID- 24044121
TI  - Lasker Foundation honours cochlear-implant pioneers.

PMID- 24044122
TI  - Lasker Foundation awards neurotransmitter researchers.

PMID- 24044123
TI  - Aid agencies accused of ignoring rights abuses in Ethiopia.

PMID- 24044124
TI  - Shakespeare and the history of heartbreak.

PMID- 24044125
TI  - Response.

PMID- 24044126
TI  - Response.

PMID- 24044127
TI  - Response.

PMID- 24044129
TI  - [What it your diagnosis? Cutaneous lymphoid hyperplasia].

PMID- 24044130
TI  - [What is your diagnosis? Primary cutaneous lymphoma with marginal zone cells].

PMID- 24044131
TI  - In response.

PMID- 24044132
TI  - In response.

PMID- 24044133
TI  - Authors' reply.

PMID- 24044134
TI  - [What is your diagnosis? Follicular lymphoma, eliminating systemic disease but
      considering a diagnosis of primary cutaneous lymphoma with follicular cells].

PMID- 24044135
TI  - Learn from your failures to succeed.

PMID- 24044136
TI  - [Comparative analysis of three length based methods for estimating growth of the
      tilapia Oreochromis aureus (Perciformes: Cichlidae) in a tropical lake of
      Mexico].
AB  - A comparative analysis of three length based methods for estimating growth of the
      tilapia Oreochromis aureus (Perciformes: Cichlidae) in a tropical lake of Mexico.
      Several methods are now available to estimate fish individual growth based upon
      the distribution of body lengths in a population. Comparative analyses of length
      based methods have been undertaken mainly for marine species; nevertheless,
      limited information is available for inland species. Tilapia is one of the most
      important freshwater fisheries and its growth parameters have been estimated by
      several authors, usually using one length-based method. Thus, the main objectives
      of this study were: a) to estimate growth parameters of O. aureus from Chapala
      lake, Mexico, using three length-based methods ELEFAN, PROJMAT and SLCA; b) to
      quantify the effect of input data variations in growth parameters estimates by
      the jackknife technique; and c) to compare the new estimates with those
      previously reported, through the standard growth index phi. We collected and
      analyzed a total of 1,973 specimens from commercial landings from January to
      December 2010. The three length-base methods used in the present study resulted
      in parameter estimates within the range of those reported in other studies.
      Results derived from jackknife analysis revealed lowest values in the error
      percentage and coefficient of variation for L infinity when applying ELEFAN,
      while PROJMAT showed lowest values in the precision estimators for K, which was
      very similar to ELEFAN. Estimates of the comparative growth index phi were also
      very similar to those reported for the same species when studied in different
      reservoirs. Considering our results, we suggest the use of ELEFAN rather than
      SLCA due to its accuracy to estimate growth parameters for O. aureus.

PMID- 24044137
TI  - Vet Center services. Final rule.
AB  - The Department of Veterans Affairs (VA) is establishing in regulation the
      readjustment counseling currently provided in VA's Vet Centers to certain
      veterans of the Armed Forces and members of their families, and implementing
      provisions of the Caregivers and Veterans Omnibus Health Services Act of 2010
      regarding readjustment counseling.

PMID- 24044138
TI  - Covering young adults under the Affordable Care Act: the importance of outreach
      and Medicaid expansion: findings from the Commonwealth Fund Health Insurance
      Tracking Survey of Young Adults, 2013.
AB  - There is concern that many young adults (ages 19--29) will remain without health
      insurance in 2014 despite the Affordable Care Act's reforms, including subsidized
      private coverage offered in new state marketplaces and expanded Medicaid
      eligibility. How things turn out will likely depend on outreach efforts and
      states' decisions on expanding Medicaid. Commonwealth Fund Health Insurance
      Tracking Survey data from 2011 and 2013 show increasing awareness among young
      adults of the 2010 requirement that health plans cover children under age 26. Of
      the estimated 15 million young adults enrolled in a parent's plan in the prior 12
      months, 7.8 million would not likely have been eligible to enroll prior to the
      law. Still, only 27 percent of 19-to-29-year-olds are aware of the marketplaces.
      Meanwhile, most uninsured young adults living below poverty will not have access
      to subsidized public or private insurance in states opting out of the Medicaid
      expansion.

PMID- 24044139
TI  - In states' hands: how the decision to expand Medicaid will affect the most
      financially vulnerable Americans: findings from the Commonwealth Fund Health
      Insurance Tracking Surveys of U.S. Adults, 2011 and 2012.
AB  - Between 2010 and 2012, nearly one-third (32%) of U.S. adults ages 19 to 64, or an
      estimated 55 million people, were either continuously uninsured or spent a period
      of time uninsured. Data from the 2011 and 2012 Commonwealth Fund Health Insurance
      Tracking Surveys of U.S. Adults show that people with incomes below 133 percent
      of the federal poverty level (i.e., the level that will make them eligible for
      Medicaid in 2014 under the Affordable Care Act) were uninsured at the highest
      rates. Yet, fewer than half the states are currently planning to expand their
      Medicaid programs, because the 2012 Supreme Court decision allows states to
      choose whether to expand eligibility. In those states that have not yet decided
      to expand, as many as two of five (42%) adults who were uninsured for any time
      over the two years would not have access to the new coverage provisions in the
      law.

PMID- 24044140
TI  - Hospital readmissions: measuring for improvement, accountability, and patients.
AB  - The Commonwealth Fund and the Institute for Healthcare Improvement convened 15
      experts in May 2013 to help address the current controversy over the measurement
      of hospital readmissions. Experts agreed that Medicare should, through payment
      and other means, be encouraging greater coordination of care, improvement in care
      transitions, and mitigation of risks that leave patients vulnerable to
      readmission. While the current readmissions metric is undoubtedly an imperfect
      proxy for broader health system failures, it also provides a valuable foundation
      on which to build a better policy-one that is useful for improvement, fair for
      accountability, and above all, relevant to patients.

PMID- 24044141
TI  - Time for lunch!

PMID- 24044142
TI  - Tar heel footprints in health care: Grace Emerson Terrell, MD, MMM.

PMID- 24044143
TI  - Surveillance of injuries in Eastern North Carolina following Hurricane Irene
      using emergency department data.
AB  - OBJECTIVE: Our objective was to characterize nonfatal injuries, by age groups,
      that were seen in emergency departments (EDs) in 29 selected counties in Eastern
      North Carolina following Hurricane Irene. METHODS: A descriptive evaluation using
      data from the North Carolina Disease Event Tracking and Epidemiologic Collection
      Tool (NC DETECT) was performed to identify the numbers and types of nonfatal
      injuries among individuals who sought treatment at hospital EDs. Percentages of
      reported ED visits related to external injuries in the 7 most severely impacted
      counties were compared with results in the entire 29-county region and with data
      from a reference period in 2010. RESULTS: The total number of individuals who
      sought treatment at an ED for an external cause of injury was 22.3% greater
      during the week following Hurricane Irene than during the 2010 reference week. In
      the 29-county region, the increases were primarily due to falls; in the 7-county
      region, they were primarily due to cutting and piercing incidents. Following the
      storm, injuries related to falls, adverse effects of health care, or being struck
      by an object accounted for higher proportions of injury-related ED visits in the
      7-county disaster region than in the 29-county region. LIMITATIONS: The inability
      to identify the patient's home address and the county where treatment was sought
      was a spatial limitation. Furthermore, data for urgent care visits, primary care
      doctor visits, and injuries treated at home were not included. Additionally,
      cautious inference should be made to distinguish between injuries that occurred
      as a direct result of the storm and those that occurred incidentally. CONCLUSION:
      Data from NC DETECT can be used to estimate the most common types of injuries
      seen in EDs following a natural disaster.

PMID- 24044144
TI  - Collection of family health history for assessment of chronic disease risk in
      primary care.
AB  - BACKGROUND: Family health history can predict a patient's risk for common complex
      diseases. This project assessed the completeness of family health history data in
      medical charts and evaluated the utility of these data for performing risk
      assessments in primary care. METHODS: Family health history data were collected
      and analyzed to determine the presence of quality indicators that are necessary
      for effective and accurate assessment of disease risk. RESULTS: More than 99% of
      the 390 paper charts analyzed contained information about family health history,
      which was usually scattered throughout the chart. Information on the health of
      the patient's parents was collected more often than information on the health of
      other relatives. Key information that was often not collected included age of
      disease onset, affected side of the family, and second-degree relatives affected.
      Less than 4% of patient charts included family health histories that were
      informative enough to accurately assess risk for common complex diseases.
      LIMITATIONS: Limitations of this study include the small number of charts
      reviewed per provider, the fact that the sample consisted of primary care
      providers in a single geographic location, and the inability to assess ethnicity,
      consanguinity, and other indicators of the informativeness of family health
      history. CONCLUSIONS: The family health histories collected in primary care are
      usually not complete enough to assess the patient's risk for common complex
      diseases. This situation could be improved with use of tools that analyze the
      family health history information collected and provide risk-stratified decision
      support recommendations for primary care.

PMID- 24044146
TI  - The Affordable Care Act. Introduction.

PMID- 24044145
TI  - Development and validation of a primary care-based family health history and
      decision support program (MeTree).
AB  - INTRODUCTION: Family health history is a strong predictor of disease risk. To
      reduce the morbidity and mortality of many chronic diseases, risk-stratified
      evidence-based guidelines strongly encourage the collection and synthesis of
      family health history to guide selection of primary prevention strategies.
      However, the collection and synthesis of such information is not well integrated
      into clinical practice. To address barriers to collection and use of family
      health histories, the Genomedical Connection developed and validated MeTree, a
      Web-based, patient-facing family health history collection and clinical decision
      support tool. MeTree is designed for integration into primary care practices as
      part of the genomic medicine model for primary care. METHODS: We describe the
      guiding principles, operational characteristics, algorithm development, and
      coding used to develop MeTree. Validation was performed through stakeholder
      cognitive interviewing, a genetic counseling pilot program, and clinical practice
      pilot programs in 2 community-based primary care clinics. RESULTS: Stakeholder
      feedback resulted in changes to MeTree's interface and changes to the phrasing of
      clinical decision support documents. The pilot studies resulted in the
      identification and correction of coding errors and the reformatting of clinical
      decision support documents. MeTree's strengths in comparison with other tools are
      its seamless integration into clinical practice and its provision of action
      oriented recommendations guided by providers' needs. LIMITATIONS: The tool was
      validated in a small cohort. CONCLUSION: MeTree can be integrated into primary
      care practices to help providers collect and synthesize family health history
      information from patients with the goal of improving adherence to risk-stratified
      evidence-based guidelines.

PMID- 24044147
TI  - Implementing the Affordable Care Act in North Carolina: the rubber hits the road.
AB  - The health insurance mandate, perhaps the best-known provision of the Patient
      Protection and Affordable Care Act of 2010 (ACA), is slated to go into effect on
      January 1, 2014. Yet most people do not know how the ACA will affect them. More
      than one-third of people in a recent national poll were unaware that new health
      insurance marketplaces will make it easier to purchase coverage or that some
      people will qualify for subsidies to help them purchase coverage. The ACA
      includes many other provisions that will have a profound impact on our health
      care delivery system. Some changes are already helping to break down silos in the
      delivery of care. Groups of health care professionals are working together to
      manage the health of populations. The ACA places a much greater emphasis on
      measuring quality and on paying health professionals and health care institutions
      based on the value of the services they provide. In addition, the ACA makes
      greater investments in prevention and in population health management. This issue
      brief highlights some of the health system changes that have taken place over the
      past 3 years, as well as some of the potential changes that are yet to come
      relating to insurance coverage, access to care, quality of care, rising health
      care costs, and overall population health.

PMID- 24044148
TI  - Shopping for health insurance in North Carolina's federally facilitated
      marketplaces.
AB  - North Carolina policymakers had initially planned for North Carolina to run its
      own health insurance marketplaces, but they have since decided to leave the
      operation of the marketplaces to the federal government alone. This article
      explores what it will mean for North Carolina to have federally facilitated
      marketplaces.

PMID- 24044149
TI  - Informing consumers about North Carolina's new federally facilitated health
      insurance marketplace.
AB  - This fall, the federal government will operate a new health insurance marketplace
      in North Carolina. Uninsured individuals will have the opportunity to purchase
      health insurance, but many of these individuals do not understand health
      insurance options and will need education and assistance in the selection of an
      insurance plan. This article describes the various ways in which this assistance
      will be provided.

PMID- 24044150
TI  - North Carolina's county departments of social services in a season of change.
AB  - Every day staff members of county departments of social services are processing
      new applications, applying changes to established cases, and juggling constant
      telephone and walk-in traffic. There is a delicate balance between this
      evergrowing workload and the availability of skilled personnel to meet these
      demands.

PMID- 24044151
TI  - Implementation of the Affordable Care Act poses challenges for insurers and
      consumers.
AB  - Later this year, new provisions of the Patient Protection and Affordable Care Act
      of 2010 will transform the health care industry. Consumers will be able to
      purchase insurance through health insurance marketplaces, but many people who
      already have insurance could see their premiums rise. Insurers will need to help
      consumers navigate the new system.

PMID- 24044152
TI  - How the patient protection and Affordable Care Act will affect employers.
AB  - This article provides an employer's perspective on the Patient Protection and
      Affordable Care Act of 2010. Since this act was implemented, it has significantly
      impacted how employers have been planning for and providing health insurance to
      their employees.

PMID- 24044153
TI  - How the Affordable Care Act will affect access to health care in North Carolina.
AB  - Reforming health care in the United States often focuses on improving access to
      care by removing financial barriers and bringing practitioners closer to
      patients. This article reviews the provisions of the Patient Protection and
      Affordable Care Act of 2010 (ACA) that are intended to improve access and
      discusses how the ACA will change access to care for Americans.

PMID- 24044154
TI  - Federally qualified health center expansion through the Affordable Care Act.

PMID- 24044155
TI  - The potential impact of the Affordable Care Act on population health in North
      Carolina.
AB  - The need to improve population health is critical. This commentary explores how
      the Patient Protection and Affordable Care Act of 2010 (ACA) can help us improve
      population health, highlights some of the actions North Carolina has taken in
      response to the ACA's provisions, and discusses the value of health investments
      in the future.

PMID- 24044156
TI  - Refusing our default future: organizations that are accountable for care can
      lower costs and improve quality.
AB  - Models of health care payment and delivery are being rapidly transformed. In
      North Carolina, multiple organizations are involved in this redesign. Cornerstone
      Health Care has reorganized its care models and renegotiated its contracts in
      order to improve the quality and lower the cost of health care.

PMID- 24044157
TI  - Laying a foundation for success in the Medicare hospital value-based purchasing
      program.
AB  - The Centers for Medicare & Medicaid Services (CMS) is seeking to transform
      Medicare by purchasing "value" from health care providers and physicians. At
      Vidant Medical Center, we have begun to link the requirements of the CMS Value
      Based Purchasing Program to the goals and objectives embedded within our quality
      improvement initiatives.

PMID- 24044158
TI  - The bundled payments for care improvement initiative at Firsthealth Moore
      Regional Hospital.

PMID- 24044159
TI  - County-level estimates of the number of individuals in North Carolina who would
      be eligible for coverage under the Affordable Care Act's expanded insurance
      options.

PMID- 24044160
TI  - Aligning efforts to meet community health needs: Collaboration in Rockingham
      County.

PMID- 24044161
TI  - Convening community conversations that matter.

PMID- 24044162
TI  - The North Carolina Oral Health Action Plan for children enrolled in Medicaid and
      NC Health Choice..

PMID- 24044163
TI  - Menopausal muddle.

PMID- 24044164
TI  - The Angelina effect.

PMID- 24044165
TI  - [A comparison of chest radiographs between patients with pulmonary Mycobacterium
      kansasii infection and those with Mycobacterium tuberculosis infection in the
      initial stage of disease].
AB  - OBJECTIVES: To elucidate the differences in affected lung segments between
      patients with pulmonary M. kansasii infection and those with M. tuberculosis
      infection in the initial stage of disease, we examined chest radiography images
      and CT scans. The initial stage of disease was defined as the period when less
      than one-sixth of the total lung area was affected by the infection, as
      visualized on chest radiography and CT. SUBJECTS AND METHODS: One hundred eighty
      four patients were diagnosed with M.kansasii infection between 1996 and 2010 and
      835 patients, with M.tuberculosis infection between 2008 and 2009 at our
      hospital. The diagnosis was made on the basis of the results of sputum culture
      and/or bronchial washing. After excluding the patients with underlying lung
      diseases such as chronic pulmonary emphysema, interstitial pneumonia, and old
      pulmonary tuberculosis as well as those in advanced stages, 24 patients with M.
      kansasii infection and 62 patients with M. tuberculosis infection were included
      in this study. The affected segments of the lungs and the rates of cavity
      development were determined by using CT scans. RESULTS: In patients with
      M.kansasii, 17 had an infected right lung, while 7 had an infected left lung.
      Additionally, in patients with M.tuberculosis, 58 had an infected right lung, 3
      had an infected left lung, and 1 had a bilateral infection. In patients infected
      with M. kansasii, the upper lobes were affected in 22 cases and the lower lobes
      in 3 cases. In patients infected with M. tuberculosis, the upper, middle, and
      lower lobes and the lingular segment were affected in 41, 8, 24, and 1 cases,
      respectively. Upper lobe lesions were seen more frequently in patients with M.
      kansasii infection than in those with M. tuberculosis infection (p < 0.05).
      Cavity formation was identified more frequently in patients infected with M.
      kansasii (91.7%) than in those infected with M. tuberculosis (32.3%) (p < 0.001).
      Cavitary lesions were more frequently localized to the apical, posterior, and
      apico-posterior regions (S1, S2 or S1 +2) of the upper lobes in patients infected
      with M. kansasii (86.4%) than in those infected with M. tuberculosis (35%) (p <
      0.001). A solitary lesion without endobronchial spread, which is characterized by
      centrilobular micronodules and tree-in-bud appearance, was more frequently
      demonstrated in patients infected with M.ka nsasii (45.8%) than in those infected
      with M. tuberculosis (6.5%) (p < 0.001). CONCLUSION: Our study revealed that the
      apical, posterior, and apico-posterior regions of the upper lobes are vulnerable
      to infection by not only M.tu berculosis, but also M.ka nsasii. It is likely that
      M.ka nsasii might gain access to these regions via the airways and that its weak
      virulence may lead to higher localization.

PMID- 24044166
TI  - [Clinical experience using rifabutin for treating infection with Mycobacterium
      tuberculosis in elderly Japanese patients].
AB  - OBJECTIVES: To clarify whether rifabutin (RBT) can be used for treating
      tuberculosis in elderly Japanese patients in the clinical setting. METHOD: We
      performed a clinical chart review from Oct 2008 to Dec 2011, for patients who
      were diagnosed with tuberculosis and were prescribed rifabutin, at the Fukujuji
      Hospital (180 beds for respiratory medicine, including 60 for TB). Primarily, we
      focused on characteristics of patients, the cause for RBT indication, and success
      rate of treatment. RESULTS: During the study period, 1129 patients were diagnosed
      with tuberculosis, and among these, 42 (3.7%) patients were prescribed RBT. Of
      these, 39 patients were included in this study (3 were excluded because their
      prescription was terminated within 2 weeks because of reasons other than adverse
      effects). In all, 69% patients were male. Mean age was 69 years, and mean body
      mass index was 19.1 +/- 3.4 kg/m2. RFP-related adverse effects were observed in
      28 patients (72%; age, 73 years); these included gastrointestinal complications
      in 16, liver dysfunction in 7, skin rashes in 6, and renal dysfunction and
      thrombocytopenia in 1 each). Additional medication was required in 6 patients,
      and RBT-resistant TB was noted in 5 patients (28%; age, 60 years). A success rate
      of 71.4% was observed in cases of RFP-related adverse effects, and that of 81.8%
      was observed in cases of other reasons. Except for the patient who experienced
      renal dysfunction, RBT could be used in all patients who experienced RFP-related
      adverse effects. CONCLUSION: RBT showed a relatively good success rate, even in
      patients who experienced RFP-related adverse effects. Thus, RBT could be an
      alternative in cases of RFP-related adverse effects, even in elderly patients.

PMID- 24044167
TI  - [A case of miliary tuberculosis complicated by a tuberculous aneurysm of the
      thoracic aorta].
AB  - An 85-year-old woman was admitted to our hospital with the chief complaint of
      fever. Antibiotics were not effective and a chest computed tomography scan
      revealed a diffuse micronodular shadow and thoracic aortic aneurysm.
      Subsequently, a bronchoscopy sputum culture was positive for Mycobacterium
      tuberculosis. Two months after the initiation of chemotherapy, the thoracic
      aortic aneurysm enlarged despite the improvement in lung findings. Tuberculous
      aneurysms are quite rare, but can be critical and acute. Therefore, caution
      should be exercised when treating such patients.

PMID- 24044168
TI  - [Usefulness of thoracoscopy under local anesthesia in the diagnosis of
      tuberculous pleurisy occurring during infliximab administration: a case report].
AB  - We report the case of a 71-year-old man with rheumatoid arthritis. Infliximab
      administration was started as treatment for rheumatoid arthritis in January 2009.
      As he showed a positive result for the tuberculin test, he was treated with
      isoniazid for 9 months. He was subsequently referred to our department in October
      2011 with a right-sided pleural effusion. When thoracoscopy was performed under
      local anesthesia, white and red protruding lesions of various sizes were observed
      in the pleural cavity. A biopsy revealed fibrous granulation tissue, and tissue
      culture and all sensitivity tests were positive for Mycobacterium tuberculosis.
      Therefore, thoracoscopy is useful for not only diagnosis but also determining
      whether resistant tuberculosis is present.

PMID- 24044169
TI  - [Tuberculosis annual report 2011--(3) case finding and condition of tuberculosis
      on diagnosis].
AB  - Tuberculosis (TB) case findings in 2011 were reviewed, particularly regarding how
      the cases were detected, the diagnostic delay, the proportion of far-advanced
      cavitary lesions, coexisting HIV infection and diabetes mellitus (DM), and drug
      susceptibility testing (DST) using the national TB surveillance database. Among
      the 22,681 TB patients newly notified in 2011, 82.1 % of the cases were detected
      when the patient sought healthcare or attended medical facilities because of
      other chief complaints. Among the 17,519 pulmonary TB patients, 25.6% had only
      respiratory symptoms, 32.2% had both respiratory and nonrespiratory symptoms, and
      17.0% had only non-respiratory symptoms. The rest (24.5%) were asymptomatic. The
      prevalence of patient's and doctor's delays among the 13,108 symptomatic
      pulmonary TB cases were analyzed. A large proportion-approximately 25-30%--of
      symptomatic pulmonary TB patients aged 30-59 years exhibited a total delay (i.e.,
      the sum of the patient's and doctor's delays) of over 3 months. The proportion of
      patients with a patient's delay of over 2 months exhibited a similar tendency to
      that of the total delay, decreasing after 60 years of age. Moreover, the
      proportion of patients aged 65 years or more with a doctor's delay of over 1
      month was higher than that of patients aged below 65 years. There was a high
      proportion-approximately 30%--of symptomatic smear-positive TB patients aged less
      than 60 years with a total delay of over 3 months, caused by a longer patient's
      delay. Meanwhile, the proportion of patients--approximately 15%--with a doctor's
      delay of over 1 month was almost stable across all age groups. The proportion of
      cases with far-advanced cavities in the lungs of pulmonary TB patients increased
      from 1.5% in 1975, remained stable at approximately 2% from 1985-2007, and
      decreased slightly thereafter until 2011 to 1.8%. From 2007-2011, there were 304
      newly notified TB cases with HIV infection, 263 (86.5%) and 41 (13.5%) of which
      were men and women, respectively, including 67 (22.0%) foreigners. The proportion
      of newly notified TB cases with DM in 2011 was 13.7% (3,117/22,681) in total,
      16.1% (2,250/3,117) in men, and 10.0% (867/3,117) in women. The results of DST
      were obtained for 8,046 (73.7%) out of 10,915 culture-positive pulmonary TB cases
      through the surveillance system in 2011. In previously untreated cases, the
      proportions of multi-drug resistant TB, any isoniazid resistance, and any
      rifampicin resistance were 0.5%, 4.1%, and 0.8%, respectively; meanwhile, in
      previously treated cases, the proportions were 3.3%, 12.1%, and 4.2%,
      respectively. In previously untreated cases, the proportions mentioned above have
      been stable over the past 5 years (2007-2011). Meanwhile, in previously treated
      cases, the proportions have decreased over the past 5 years, except for those
      exhibiting any isoniazid resistance (11.4% in 2010 to 12.1% in 2011).

PMID- 24044170
TI  - [Computed tomography image analysis of peritonsillar abscess].
AB  - The peritonsillar abscess (PTA) is one of the most common infectious diseases in
      the head and neck area and is treated with puncture, incision, or abscess
      tonsillectomy. In the present study, we performed a retrospective study for the
      patients who were diagnosed as having PTA on the basis of CT findings at the
      Kagoshima University Hospital between January 2007 and April 2012. The clinical
      characteristics were compared with the CT images and the indication of abscess
      tonsillectomy was discussed. In total, 145 patients (152 sides), mean age of 41
      years (range: 5-80 years) were enrolled in the study. Patients having any
      surgical treatment such as puncture and incision before visiting our hospital
      were excluded. The CT findings revealed that PTA could be classified into two
      categories by the shapes of the abscess: the Oval type and Cap type. Further, the
      location of the abscess was differentiated superior and inferior, and classified
      into 4 categories: superior Oval type, superior Cap type, inferior Oval type, and
      inferior Cap type. The results showed that the number of the superior Oval type
      PTA was largest and followed by superior Cap type, inferior Cap type, and
      inferior Oval type in this order. When the CT classifications were compared with
      clinical findings, patients with the inferior Cap type abscess had laryngeal
      edema and airway obstruction more frequently than the other categories of PTA.
      Histological examination of the specimens obtained during surgery showed that the
      Cap type abscess tended to include more muscular tissue compared to the Oval
      type, indicating that inflammation might be more severe and wider in the Cap type
      than the Oval type. Those findings suggest that the inferior Cap type of PTAs
      need more intensive and reliable treatments such as abscess tonsillectomy.

PMID- 24044171
TI  - [The clinical features of migraine-associated vertigo].
AB  - Migraine-associated vertigo (MAV) is proposed as a new clinical entity on the
      basis of the assumption that the typical migraine and vertigo or dizziness have a
      common pathophysiology. Some of the patients with recurrent vertigo syndromes
      with unknown pathology may have MAV. We performed a retrospective study to
      clarify the clinical characteristics of MAV in the Japanese population. The
      following were considered as diagnostic criteria: (1) recurrent vestibular
      symptoms, (2) migraine headache as defined by the International Headache Society
      (IHS) criteria, (3) at least one instance of synchronization of a vertiginous
      attack with a migraine headache, (4) no associated unilateral hearing loss, and
      (5) absence of other diseases that may have caused vertiginous attacks. Of 552
      patients with dizziness or vertigo, 46 (8.3%) were diagnosed as having MAV. A
      typical feature of this clinical entity is that migraine occurs before the onset
      of vertigo in women aged 30-40 years. Usually the attacks occur once in a year
      for 1 to 10 years. An attack lasts for 1-24 h and presents as vertigo and
      unsteadiness with simultaneous headache. The presence of hearing loss presents an
      important clinical dilemma. Whether the condition in patients experiencing
      hearing loss should be defined as MAV or not is still a matter for discussion.

PMID- 24044172
TI  - [Endolymphatic hydrops detected with inner ear gd contrast-enhanced MRI;
      comparison between administration routes or with ECochG or glycerol test].
AB  - OBJECTIVE: Gadolinium (Gd) contrast-enhanced MRI has recently been introduced to
      clinical practice to detect endolymphatic hydrops. However, since the image
      depends on the hardware, pulse sequence or the way of Gd administration, the
      protocol and the evaluating criteria for hydrops on MRI have not yet been
      standardized. In this study, we assessed the usefulness of the hydrops detection
      by MRI following the intratympanic or intravenous Gd administration methods, and
      compared these findings with the electrocochleography and glycerol test. METHODS:
      MRI was taken in 27 patients with Meniere's disease or delayed endolymphatic
      hydrops. All patients had frequent episodes of vertigo attacks which were
      clinically considered as of unilateral ear origin. Two types of Gd administration
      were used; injection into the tympanic cavity in 17 patients or intravenous
      injection in 10 patients. Axial 2D-FLAIR images were obtained with a 3.0T MRI
      unit, 24 and 4 h after intratympanic or intravenous administration, respectively.
      The endolymphatic space was detected as a low signal intensity area, while the
      surrounding perilymphatic space showed high intensity with Gd contrast. Those
      cases in which low signal areas corresponding to the cochlear duct could be
      clearly noticed, were classified as cochlear hydrops. When the greater part of
      the vestibule was occupied by a low signal area in more than half of the images,
      it was classified as vestibular hydrops. RESULTS: Endolymphatic hydrops was
      detected in 88% (15/17 cases) by the intratympanic Gd administration method, and
      90% (9/10) by the intravenous method. In the contralateral ears, 20% (2/10)
      showed hydrops, detected by the intravenous method. ECochG and the glycerol test
      were difficult when the hearing of the patient was severely impaired. Positive
      results of EcochG and the glycerol test were obtained only in 15 and 6 cases,
      respectively. However, as far as the waves could be obtained, ECochG showed a
      high detection rate of 88% (15/17) in the affected ear. In those cases in which
      both MRI and EcochG could be obtained, including both ears, the results were
      matched in 78% (21/27ears). CONCLUSION: For the qualitative detection of hydrops,
      intratympanic and intravenous Gd administration methods were equivalent. Inner
      ear Gd contrast-enhanced MRI had higher efficacy in the detection of hydrops than
      the conventional tests.

PMID- 24044173
TI  - [A case of steroid psychosis caused by treatment for acute sensorineural hearing
      loss].
AB  - A 36 y/o female presented with the chief complaint of diarrhea and vomiting which
      had lasted for four days, and with a family history of suicide. The first general
      examination showed severe dehydration with hyponatremia. After admission, she was
      diagnosed as having isolated adrenocorticotropic hormone (ACTH) deficiency and
      mixed connective tissue disease, and the steroid replacement therapy was started
      with the dose equivalent to 7.5 mg/day of prednisolone (PSL). Three days later,
      she had right sensorineural hearing loss (SNHL). She was given 40 mg/day PSL in
      addition to the steroid replacement therapy. On the next day, she developed a
      persecutory type of paranoid disorder, and then was given psychiatric medication.
      After tapering off PSL for SNHL, the delusion began to improve with psychiatric
      medication. Three weeks after the onset of SNHL, her hearing level had partially
      recovered. Ten months later, she did not show any psychic instability. A family
      history of psychosis and the present history of malnutrition and connective
      tissue disease are risk factors of steroid psychosis. It can develop even with 5
      mg PSL if the patient has a risk factor. Careful medical history taking and
      knowledge about the steroid psychosis will prevent the severe side effects
      associated with steroid treatment.

PMID- 24044174
TI  - Make the FDA an organization dentists want to belong to!

PMID- 24044175
TI  - Diagnostic discussion. Secondary or recurrent herpetic stomatitis.

PMID- 24044176
TI  - A view of the profession: from student to dentist to seasoned veteran--a 25-year
      perspective.

PMID- 24044177
TI  - Email texting: make certain electronic communications ensure patient privacy.

PMID- 24044178
TI  - Pride in excellence: avoiding burnout.

PMID- 24044179
TI  - [Despite the absence of TWAR outbreak--"the Gunde Svan effect" remains].

PMID- 24044180
TI  - [Tranexamic acid--an old drug in a new costume. Multinational studies and new
      texts provide a boost for the antifibrinolytic agent].

PMID- 24044181
TI  - [Pathological collecting is a new diagnosis in DSM-5. Condition with high somatic
      and psychiatric comorbidity that is difficult to treat].

PMID- 24044182
TI  - [Data analysis of elderly patients with Apodos. Inferior pharmacotherapy with
      many prescribers].

PMID- 24044183
TI  - [Hyperthyroidism induced by iodine contrast media is hard to treat. Can lead to
      delayed therapy of tumors, as shown in two cases].

PMID- 24044184
TI  - [Fast track assessment of lung cancer cut the investigation time in half].

PMID- 24044185
TI  - [Important with generous sampling for hepatitis C after blood transfusion. The
      National Board of Health and Welfare's new recommendation for risk groups].

PMID- 24044186
TI  - [The narrative is important in health checks of young asylum seekers].

PMID- 24044188
TI  - [Poisonous reading].

PMID- 24044187
TI  - [Treatment with cinacalcet in secondary hyperparathyroidism for dialysis
      patients: The will is good--but what about the evidence?].

PMID- 24044189
TI  - Washington changes tides of healthcare reform.

PMID- 24044190
TI  - The triple aim in specialty care: using existing data to measure quality.
AB  - Medical provider organizations are being pushed by regulators, payers, and
      consumers to report on quality and outcomes in the delivery of healthcare. This
      is intensified when financial incentives are applied to the results. Providers
      are challenged to contribute to the definition of quality because of their
      patient care obligations and the work of staying current in running their medical
      practices. One medical practice faced the challenge by developing a process for
      reporting on quality. Its experience and outcomes describe a manner that can be
      successful for other physician groups looking to do the same.

PMID- 24044191
TI  - How sequestration cuts affect primary care physicians and graduate medical
      education.
AB  - On April 1, 2013, sequestration cuts went into effect impacting Medicare
      physician payments, graduate medical education, and many other healthcare
      agencies. The cuts range from 2% to 5%, affecting various departments and
      organizations. There is already a shortage of primary care physicians in general,
      not including rural or underserved areas, with limited grants for advanced
      training. The sequestration cuts negatively impact the future of many primary
      care physicians and hinder the care many Americans will receive over time.

PMID- 24044192
TI  - The paradox of parity: limitations in the breakthrough law for mental health
      equality.
AB  - The intent of parity laws is to improve equity in private insurance coverage for
      mental health care. The groundbreaking legislation of the 1996 Mental Health
      Parity Act (MHPA) was initially hailed as a major achievement in improving mental
      health coverage. However, research suggests that because of political compromises
      and employer exemptions, the potential impact of the MHPA was weakened. This
      paper summarizes the extent and scope of the MHPA and the 2008 Mental Health
      Parity and Addiction Equity Act, highlighting the goals and accomplishments of
      each; examines limitations of the legislation, explicitly accounting for
      exemptions, uninsured Americans, and access to care; and provides recommendations
      for further improvement and implementation of mental health coverage.

PMID- 24044193
TI  - Apology and disclosure for physicians and medical practices: what to keep in
      mind.
AB  - Disclosure and apology is an important issue in healthcare, yet physicians and
      other healthcare professionals are still struggling to conceptualize this topic.
      This article will discuss how physicians and medical practices should approach
      disclosure with their hospital system and/or insurance company, and how they can
      empathize and stay connected with their patient post-event regardless of
      insurance coverage.

PMID- 24044194
TI  - HIPAA Security Standards: getting ready for prime time.

PMID- 24044195
TI  - The health of healthcare, Part I: The right approach is medical.
AB  - Fantasize for a moment. Imagine that our healthcare system is a human being, a
      patient with a name, a family, and a mortgage who walks into your office looking
      acutely ill. How would you approach this patient? What would you do? Now consider
      what has actually been done to patient Healthcare by its treating "doctors." Is
      the patient better or worse as a result of their therapy? This series of articles
      will explore these issues, starting with the need to use a medical--rather than a
      political or financial--approach to treat patient Healthcare.

PMID- 24044196
TI  - The corpulent and sedentary society: epitome of a healthcare crisis.
AB  - Obesity is killing our patients and draining our healthcare resources. The First
      Amendment is an available tool to reverse the tragic state of our nation's
      health. Through educational programs, across all economic, educational, and
      cultural stratifications of our society, emphasizing the importance of diet and
      exercise, we can reverse the tragic physical, emotional, and health consequences
      of obesity. This must be a physician-led strategy that empowers patients across
      all age groups to be personally responsible for their personal health.

PMID- 24044197
TI  - Clinical and safety considerations for moderate and deep sedation.
AB  - The need for anesthesia services is increasing both in and out of the operating
      room. Ideally, individuals with the most training and experience with sedation
      would administer it. Due to the high volume of cases that require sedation,
      however, many non-anesthesiologists are providing this service. It is important
      for sedation providers to realize there are several different levels of sedation,
      but that clinically it may be difficult to differentiate among them. Sedation
      providers must demonstrate sufficient knowledge regarding the preprocedural
      evaluation, the necessary monitors and equipment availability, the commonly
      administered medications and their reversal agents, and when a patient has
      recovered from sedation and can appropriately be discharged. Each institution
      offering sedation services must follow the federal and state regulations on
      moderate and deep sedation, and sedation providers must have the appropriate
      qualifications. The specific education and training required of sedation
      providers differs among institutions. Although most institutions adopt the
      guidelines and standards of the American Society of Anesthesiologists, each
      professional society also has its own set of guidelines. In the end, whether
      sedation is administered by anesthesia or non-anesthesia providers, patient
      safety is of utmost concern.

PMID- 24044198
TI  - Gruntling the disgruntled.

PMID- 24044199
TI  - Barriers to entry or exit: which ones are you building?
AB  - Unknowingly, we often create barriers that make it difficult for patients to
      enter or doctors to refer to our medical practices. Additionally, we make it too
      easy for patients and referring physicians to seek care elsewhere. This article
      will focus on these barriers to entry (which we need to knock down) and exit
      (which we want to build up) for a medical practice. We will demonstrate how you
      can identify and eliminate your entry barriers to make it easy for patients to
      become a part of your practice, and how you can build defenses to make it
      unlikely that patients will leave you and to prevent referring physicians from
      calling anyone else.

PMID- 24044200
TI  - "That's not how we do it": managing the inherited medical practice team.
AB  - Most medical practice managers who take a new job will inherit an existing team.
      Those first few days on the job are critical because they can determine whether
      or not the new manager will succeed. This article provides a game plan for new
      medical practice managers so they get off on the right foot with their inherited
      teams. It suggests strategies for learning about the team's culture and for
      demonstrating visibly that there is a new manager in the job. It offers
      guidelines about introducing the new manager to the inherited team, discussing
      past experiences, and establishing new expectations. This article further
      provides practical tips for serving as a role model, gaining allies, and dealing
      with troublemakers quickly and effectively. It suggests strategies for speaking
      about the previous practice manager and for creating excitement with the
      inherited team. Finally, this article offers a set of 15 questions a new manager
      can ask members of the inherited team to get to know them, an additional 25-point
      team assessment instrument, and a step-by-step strategy for raising the bar for
      mediocre, lackluster, or dysfunctional inherited teams.

PMID- 24044201
TI  - HIPAA risk is contagious: practical tips to prevent breach.
AB  - As of January 1, 2013, the Department of Health and Human Services had reported
      81,790 breaches of patient information in healthcare affecting millions of
      patients. HIPAA fines are growing, and penalties are becoming more onerous. The
      final omnibus HIPAA and HITECH rule has been announced, and compliance dates are
      set. Now is the time for medical practices to revisit HIPAA compliance, update
      policies, and prepare to meet new requirements. This article will help your
      practice protect patient information and reduce your overall HIPAA risk.

PMID- 24044202
TI  - How HIPAA final rules affect health information technology vendors.

PMID- 24044203
TI  - The status quo has got to go.
AB  - The healthcare profession has a reputation as a very conservative occupation. As
      a result, innovation in medicine comes about very slowly. There are numerous
      examples from medical history where innovators were sanctioned and even
      ostracized for their new ideas and recommendations to make medical care for
      patients better. This also applies to the business of medicine. This article will
      discuss examples from history where doctors have attempted to advance the
      clinical aspects of medicine, receiving condemnation from their peers and
      colleagues, and ultimately receiving approval and even the Nobel Prize on several
      occasions. It will also review innovation and its implications for nonclinical
      aspects of medical care.

PMID- 24044204
TI  - "It followed me home!": caring for the boss' new pet (project).
AB  - Managers inherit unexpected--and often unwanted--projects all the time. A
      physician-partner may return from a conference with a signed contract in hand for
      a new bit of technology or a service that promises to solve great operational
      problems or provide a fresh new stream of revenue. Shrewd managers will keep
      their personal skepticism under wraps and grab the bull by the horns. Above all,
      maintain strong and open communication with the doctor who championed the project
      in the first place, involve him or her in the planning and implementation
      processes, and exercise diligence in making it work--even if you didn't agree
      with the concept in the first place.

PMID- 24044205
TI  - IRS publishes final report on 401(K) compliance.

PMID- 24044206
TI  - [Expression of neuraminidase gene of influenza virus H1N1 in baculovirus
      expression system].
AB  - OBJECTIVE: To construct the recombinant baculovirus with NA gene of Influenza
      H1N1 virus. METHODS: Full-length NA gene of Influenza virus H1N1 (A/PR/8/34) was
      amplified by PCR and inserted into pFastBacdual vector to construct the
      recombinant baculovirus transfer vector pFBD-NA. Recombinant shuttle vectors
      rBacmid-NA was then obtained after transforming DH10B competent cells containing
      bacmid plasmids. After transfecting into sf9 cells, recombinant baculovirus rBac
      NA was obtained. The rBac-NA genome was extracted and identified by PCR. NA
      protein expressed by recombinant baculovirus-infected sf9 cells was determined by
      IFA, Western Bolt and ELISA. RESULTS: PCR results proved that recombinant shuttle
      vectors rBacmid-NA was successfully constructed. NA protein was detected by IFA
      and showed strong specific green fluorescence on the surface of infected cells.
      NA protein was recognized by two polyclonal antibodies specific for NA in Western
      Blot. ELISA showed specific reaction of recombinant NA protein with mouse
      polyclonal antibody against influenza virus (PR8), indicating high antigenicity.
      CONCLUSION: Recombinant baculovirus rBac-NA that expresse NA protein of influenza
      virus was successfully constructed. This work provides a basis for further study
      on NA protein function and novel influenza vaccine development.

PMID- 24044207
TI  - [Reverse genetics platform construction of influenza pandemic virus strain].
AB  - OBJECTIVE: Reverse genetics was used to construct the platform of flu pandemic
      strain A/California/07/2009 (H1N1). METHODS: Eight genes fragements were
      amplified and ligated with bidirectional vector, recombinant plasmids were co
      transfected to the 293 T cells and rescued the virus. Gene sequencing, antigenic
      analysis and growth property were used to evaluate the rescued virus. RESULTS:
      Rescued virus show the genes sequence correct, keep the same antigenicity and
      similar growth property compared with wild type virus. CONCLUSION: The pandemic
      virus reverse genetics platform of A/California/07/2009 (H1N1) were built. Based
      on this platform, rescued virus hold the similarity of antigenicity and growth
      ability with wild type virus.

PMID- 24044208
TI  - [Prokaryotic soluble expression of protein D of Haemophilus influenzae type b].
AB  - OBJECTIVE: To express the recombinant D protein in prokaryotic expression system
      solubly and make preparation for producing D-carrier conjugate vaccine next step.
      METHODS: The hpd gene fragment removed of signal peptide from genomic DNA of Hib
      CMCC was inserted into pET43. 1a. The recombinant plasmid was transformed to
      competent E. coli BL21 (DE3) for expression under induction of IPTG. The
      expressed recombination protein was precipitated with ammonium sulfate, purified
      by DEAE anion exchange column chromatography and identified for reactogenicity by
      Western Blot. RESULTS: The expressed recombination protein, in a soluble form,
      constained about 50% of total somatic protein and showed specific reaction with
      the HIB antisera after preliminary purification. CONCLUSION: The D protein
      recombined expression plasmid was constructed successfully and expressed D
      protein in prokaryotic cells in a solube form.

PMID- 24044209
TI  - [The relationship between serum HBsAg levels and liver inflammation and fibrosis
      in patients with chronic hepatitis B].
AB  - OBJECTIVE: To investigate the relation of hepatitis B surface antigen (HBsAg)
      level with chronic hepatitis B (CHB) and liver inflammation and fibrosis.
      METHODS: A total of 301 patients who diagnosed CHB and underwent liver biopsy
      were enrolled into the study. Meantimes, the biochemical markers, ferritin
      (FERR), serum HBsAg and HBV DNA quantitation were detected. The relation between
      HBsAg level and liver pathology were determined by spearman rank correlation
      analysis. The receiver operating characteristic curve was used to evaluate the
      accuracy of HBsAg level for liver inflammation and fibrosis. RESULTS: The body
      mass index (BMI), age, gender, genotype and family history had no effective on
      liver inflammation and fibrosis (P < 0.05). With the progressing of inflammation
      and fibrosis, the serum AST and ALT raise obviously (chi2 = 71.193, 96.344,
      47.847, 63.981; P = 0.000, 0.000, 0.000, 0.000). When fibrosis reached to S4, the
      level of HBV DNA decreased obviously (chi2 = 33. 322; P = 0.000). With the
      aggravation of inflammation and fibrosis, the serum HBsAg gradually descended
      (chi2 = 68.173,15.719; P = 0.000, 0.000). The areas under operating
      characteristics curves of HBsAg predicted < or = G3 and < or = S3 were 0.732 and
      0.793, and the specificity were 0.778, 0.891, and sensitivity were 0.685, and
      0.633, respectively. CONCLUSION: The level of HBsAg of Chinese CHB patients
      descended gradually with the aggravation of liver inflammation and fibrosis. The
      serum HBsAg had a higher specificity to predict < or = G3 and < or = S3 of CHB
      patients. But there had superiority of predicting fibrosis than inflammation.

PMID- 24044210
TI  - [Virus detection in bronchoalveolar lavage fluid of 122 children with severe
      pneumonia].
AB  - OBJECTIVE: To investigate the prevalence of viral pathogen in children with
      severe pneumonia in Hunan. METHOD: Bronchoalveolar lavage fluid [BALF] were
      collected from 122 hospitalized children with severe pneumonia in People's
      Hospital of Hunan province from January 2011 to December 2011. Nested- or reverse
      transcription Polymerase chain reaction (PCR or RT-PCR) was used to screen
      Adenovirus (ADV), Human Bocavirus (HBoV), Parainfluenzaviruses1-4 (PIV1-4), Human
      Respiratory Syneytial virus (RSV), Influenza virus A (IFVA), Influenza virus B
      (IFVB), Human Rhinovirus(HRV), Human Metapneumovirus (HMPV), human coronaviruses
      NL63 and HKU1 (HCoV-NL63, HCoV- HKU1). RESULTS: Among the 122 bronchoalveolar
      lavage fluid, viral agents were detected in 60 samples(49.1%), among which ADV
      (40.98%) was the most common virus, followed by RSV (7.37%) and HBoV (7.37%). Two
      viruses were detected in 21 individual (35%) samples, of which 20 were dual
      positive for ADV (40%). CONCLUSION: ADV is the most frequently detected viral
      etiology of severe pneumonia in children in Hunan during this year. And its
      Coinfection with other respiratory viruses was common.

PMID- 24044211
TI  - [Epidemiological features on 3 important viral diarrhea among children in Zhuhai
      during winter and spring].
AB  - OBJECTIVE: To explore the epidemiological characteristics of viral diarrhea of
      norovirus (NV), sapovirus (SV) and astrovirus (AstV) among children in Zhuhai
      during winter and spring. METHODS: Stool specimens were collected from children
      with viral diarrhea in Maternal and Child Health Hospital of Zhuhai from November
      21, 2009 to April 3, 2010. Nucleic acid of NV, SV and AstV from negative
      specimens of rotavirus and adenovirus were detected by using Reverse
      transcription-polymerase chain reaction (RT-PCR), and the types of positive
      samples of NV were also classified at the same time. RESULTS: The total detection
      rate of the three viruses is 21.49 percent, the highest detection rate is 29.05%
      in December 2009, the lowest detection rate is 12.20% in February 2010, 87.96% of
      positive specimens were from children patients aged from 0 to 30 months. The
      season detection rate of NV, SV and AstV are 14.70%, 2.75% and 4.04%
      respectively. There were significant differences of NV and SV detection rates in
      every month of the season, whereas the AstV detection rate was comparatively
      stable. The highest detection rate of NV is 34.09% in children patients aged from
      12 to 18 months, the highest SV detection rate is 12.5% in children patients aged
      from 60 to 120 months, and the highest AstV detection rate is 16.67% in children
      patients aged from 24 to 30 months. All the NV were belong to G II genogroup.
      CONCLUSIONS: NV is one of the main pathogens causing viral diarrhea among
      children in Zhuhai during winter and spring, SV and AstV are also important
      pathogens. So we should strengthen the monitoring of viral diarrhea caused by NV,
      SV and AstV in infants and young children.

PMID- 24044212
TI  - [The effect of aluminum adjuvant and immunization schedule on immunogenicity of
      Sabin inactivated poliovirus vaccine].
AB  - OBJECTIVE: To study the effect of aluminume adjuvant and immunization schedule on
      immunogenicity of Sabin inactivated poliovirus vaccine. METHODS: Four batches of
      Sabin IPV were produced by different concentrations of type 1, 2, and 3
      poliovirus and administrated on three-dose schedule at 0, 1, 2 months and 0, 2, 4
      months on rats. Serum samples were collected one month after each dose and
      neutralizing antibody titers against three types poliovirus were determined by
      micro-neutralization assay. RESULTS: The GMTs of neutralizing antibodies against
      three types poliovirus increased significantly and the seropositivity rates were
      100% in all groups after 3 doses. There was no significant difference between two
      immunization schedules, and the 0, 2, 4 month schedule could induce higher level
      neutralizing antibody compared to the 0, 1, 2 month schedule. The groups with
      aluminum adjuvant could induce higher level neutralizing antibody compared to the
      groups without adjuvant. CONCLUSION: Aluminum djuvant and immunization schedule
      could improve the immunogenicity of Sabin IPV.

PMID- 24044213
TI  - [The high expression of HPV31 and 52 L2 fusion protein in E. coli and detection
      of its immunogenicity].
AB  - OBJECTIVE: To express HPV31 and 52 L2 fusion protein and detect its
      immunogenicity. METHODS: According to the amino acid sequences of HPV31 and 52 L2
      11-200AA published in the GenBank database, weartificially synthesized the HPV31
      and 52 L2 fusion gene which was optimized according to Escherichia coli codon
      usage and encodes 11-200 amino acid of HPV31 and HPV52 L2, then cloned it into
      pET-9a vector. The HPV31 and 52 L2 fusion protein was expressed in Prokaryotic
      expression system and the mice were immunized with the fusion protein after
      purification. The immunogenicity was characterized in vaccinated mice. RESULTS:
      HPV31 and 52 L2 fusion protein was highly expressed in E. coli, the amount of
      fusion protein is nearly 20% of the total bacterial protein. The purified fusion
      protein with aluminum adjuvant could induce specific high titer of IgG antibodies
      detected by ELISA, and also induce the neutralizing antibodies against
      pseudovirus of HPV31 and HPV52 and cross-neutralizing antibodies against
      pseudovirus of HPV45, 58, 16, 18. CONCLUSION: HPV31 and 52 L2 fusion protein
      could induce neutralizing and cross-neutralizing antibodies against HPV
      pseudovirus. It provides laboratory basis for development of HPV L2 protein
      vaccine.

PMID- 24044214
TI  - [Study on PrP106-126 peptide disturbed dimeration of 14-3-3beta].
AB  - OBJECTIVE: To investigate both PrP and PrP106-126 peptide effect on 14-3-3beta
      dimeration. METHODS: 14-3-3beta were incubated with different does recombinant
      PrP or PrP106-126 peptide, both 14-3-3beta dimer and polymer were separated 15%
      non-denaturing polyacrylamide gel electrophoresis (PAGE) and the 14-3-3 dimers
      were evaluated using 14-3-3beta-specific Western blotting. And then,14-3-3beta
      dimeration buffer were incubated with different does recombinant PrP and 250
      micromol/L PrP106-126 peptide, 14-3-3beta dimer and polymer were detected by
      above methods. Cellular 14-3-3 dimer were also detected after PrP106-126 peptide
      were added to HeLa cell for 8 hours. RESULTS: Recombinant full-length PrP
      facilitated the dimerization of 14-3-3beta and PrP106-126 disturbed 14-3-3beta
      dimeration as both have dose dependence effect. PrP antagonized PrP106-126
      induced 14-3-3beta dimer with PrP protein increase in vitro. Cellular 14-3-3
      dimerization also decreased after treatment of peptide PrP106-126 on HeLa cells
      for 8 hours. CONCLUSION: [corrected] Dimerization process of 14-3-3beta was
      promoted by full-length PrP (PrP23-231) but inhibited by peptide PrP106-126 in
      vitro. PrP agonized PrP106-126-induced inhibition of 14-3-3 dimeration. PrP106
      126 inhibited cellular 14-3-3 dimerization.

PMID- 24044215
TI  - [Dendritic cell subsets and function in newborns from mothers of different HBV
      infection status].
AB  - OBJECTIVE: The aim of this study was to explore the frequency of mDC and pDC and
      expression of surface markers of the neonates and to discuss the effect of
      different status of HBV infection of mother on biological characteristics of DC.
      METHODS: Umbilicus cord blood in neonates of HBeAg positive HBV infected mother,
      HBeAg negative HBV infected mother, and normal mother were collected
      respectively; peripheral blood of healthy adults were selected as control group.
      Flow cytometry was employed to detect frequency of the mDC and its expression of
      CD86, frequency of pDC and its expression of CD80, CD83, CD86, and FlowJo
      software was used to compare these indicators among the groups. RESULTS: Compared
      with control group, the frequency of mDC of cord blood (0.29 +/- 0.16 vs 0.81 +/-
      0.17), CD86 positive rate of mDC (10.72 +/- 10.01 vs 32.13 +/- 7.46), the
      frequency of pDC (0.15 +/- 0.07 vs 0.30 +/- 0.07), and CD86/CD83 positive rate of
      pDC (31.61 +/- 12.81 vs 74.96 +/- 9.78; 42.66 +/- 20.83 vs 82.00 +/- 6.94) were
      lower (t = -7.86, P = 0.00; t = -5.36, P = 0.00; t = -5.43, P = 0.00; t = -8.49.
      P = 0.00; t = -4.90, P = 0.00). CONCLUSIONS: The frequency of mDC and pDC in
      umbilical cord blood was lower than the peripheral blood of healthy adult, which
      was the possible mechanism of newborns easier to chronicity after the infection
      of hepatitis B virus. A significant correlation was found between different
      status of HBV infection and costimulatory molecule CD86 positive rate of mDC, but
      not for the frequency of mDC and pDC, and the expression of pDC molecules.

PMID- 24044216
TI  - [Efficacy of Peg-interferon alpha-2a combinated with entecavir on HBeAg positive
      chronic hepatitis B patients with high serum hepatitis B viral loads].
AB  - OBJECTIVE: This study aimed at evaluating the efficacy and safety of a
      combination treatment of entecavir and Peginterferon alpha-2a for HBeAg positive
      chronic hepatitis B patients with high serum hepatitis B viral loads. METHODS: 60
      treatment-naive HBeAg-positive CHB patients with high serum hepatitis B viral
      loads were enrolled and randomly divided into three groups: group A received
      Peginterferon alpha-2a monotherapy for 48 weeks (n = 20); group B received
      entecavir monotherapy for more than 48 weeks (n = 20); group C received
      Peginterferona alpha-2a combined with entecavir for 12 weeks, then Peginterferon
      alpha-2a monotherapy for 36 weeks (n = 20). Virological response, ALT
      normalization, HBeAg and HBsAg seroclearance rate were analysed at the end of 4,
      12 and 24 weeks after the treatment. RESULTS: The ratio of undetectable hepatitis
      B virus (HBV) DNA were 50% and 10%, 95% and 25% and 100% and 30% in group C and
      group A respectively, 50% and 20%, 95% and 75% and 100% and 90% in group C and
      group B respectively at the end of 4, 12 and 24 weeks of treatment. The
      differences were significant between group C and A (Z = -4.6, P < 0.001), group C
      and B (Z = -2.53, P = 0.0114). ALT normalization rate was significantly lower in
      group A than that of group C (Z = -2.63, P = 0.0086). HBeAg levels declined more
      in group C than the other two groups after 24 weeks of treatment. CONCLUSIONS:
      For HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral
      loads, combination treament of Peginterferon alpha-2a with entecavir is more
      effective than Peginterferon alpha-2a monotherapy in virologic response and ALT
      normalization after 24 weeks of treatment.

PMID- 24044217
TI  - [Prognostic significance of serum anti-Epstein-Barr virus antibodies in
      nasopharyngeal carcinoma].
AB  - OBJECTIVE: This study was aimed to investigate the association between serum
      against Epstein-Barr virus (EBV) antibodies levels and nasopharyngeal carcinoma
      (NPC) patients' prognosis. METHODS: Blood samples from 140 primary NPC patients
      without metastasis were collected before and after treatment. The titers of
      VCA/IgA and EA/IgA were detected by immunoenzyme assay, and the levels of NA1/IgA
      and Rta/IgG were detected by enzyme-linked immunosorbent assay (ELISA). All
      patients received consequent follow-up and long-term efficacy and survival
      assessment. RESULTS: Post-treatment serum levels of VCA/IgA, EA/IgA, NA1/IgA and
      Rta/IgG in NPC patients significantly decreased than those before treatment,
      while had significantly higher than those in control individuals (P < 0.05).
      Patients in remission had significantly lower pre-treatment serum levels of
      VCA/IgA and EA/IgA than patients with progression (P < 0.05). None of serum
      levels of VCA/IgA, EA/IgA, NA1/IgA and Rta/IgG was associated with the 3-year
      overall survival (P > 0.05). The progression-free survivals were significantly
      lower in patients with higher pre-treatment VCA/IgA (> or = 1 : 320) and EA/IgA
      (> or = 1:80) levels than in those with lower VCA/IgA ( < 1 : 320) and EA/IgA (<
      1 : 80) levels, respectively (61.8% vs. 86.5% , 61.3% vs. 86.5%, P < 0.001). Cox
      regression model analysis demonstrated that pre-treatment serum VCA/IgA level was
      an independent risk factor for progression-free survival (HR = 3.80, P = 0.001).
      CONCLUSION: Anti-EBV VCA/IgA and EA/IgA might provide information regarding the
      prognosis of NPC patients.

PMID- 24044218
TI  - [Identification of Env-specific monoclonal antibodies from Chinese HIV-1 infected
      person by magnetic beads separating B cells and single cell RT-PCR cloning].
AB  - OBJECTIVE: To establish a simple and practical method for screening of Env
      specific monoclonal antibodies from HIV-1 infected individuals. METHODS: Human B
      cells were purified by negative sorting from PBMCs and memory B cells were
      further enriched using anti-CD27 microbeads. Gp120 antigen labbled with biotin
      was incubated with memory B cells to specifically bind IgG on cells membrane. The
      memory B cells expressing the Env-specific antibody were harvested by magnetic
      beads separating, counted and diluted to the level of single cell in each PCR
      well that loading with catch buffer containing RNase inhibitor to get RNAs. The
      antibody genes were amplified by single cell RT-PCR and nested PCR, cloned into
      eukaryotic expression vectors and transfected into 293T cells. The binding
      activity of recombinant antibodies to Env were tested by ELISA. RESULTS: Three
      monocolonal Env-specific antibodies were isolated from one HIV-1 infected
      individual. CONCLUSION: We can obtain Env-specific antibody by biotin labbled
      antigen, magnetic beads separating technique coupled with single cell RT-PCR and
      expression cloning.

PMID- 24044219
TI  - [Visual detection of HIV-1 by reverse transcription loop-mediated isothermal
      amplification with the hydroxynaphthol blue dye].
AB  - OBJECTIVE: A reverse transcription loop-mediated isothermal amplification (RT
      LAMP) assay was developed for rapid visual detection of HIV-1. METHODS: RT-LAMP
      primers were designed according to conservative sequences of HIV-1 gag gene, and
      their sensitivity and specificity were evaluated by the established RT-LAMP
      protocol with the addition of the hydroxynaphthol blue (HNB) dye prior to
      amplification. The performance of RT-LAMP on clinical samples was compared with
      real-time reverse transcription PCR(qRT-PCR). RESULTS: The RT-LAMP assay showed a
      high specificity, and its detection limit was 1000 copies RNA per tube. The
      sensitivity and specificity of this method using 43 clinical samples were 94.6%
      and 100%, respectively,in comparison with those of qRT-PCR. CONCLUSION: RT-LAMP
      assay using hydroxynaphthol blue dye does not need expensive instruments, and
      offer an alternative for the rapid detection of HIV-1 with the potential to be
      applied in field diagnosis.

PMID- 24044220
TI  - [Establishment of a purificatory method for alpha-fetoprotein variant by affinity
      adsorption].
AB  - OBJECTIVE: To establish a purificatory method of alpha-fetoprotein variant (AFP
      L3) based on microspincolumn with lens culinaris agglutinin (LCA). METHODS: LCA
      was isolated by ammonium sulfate precipitation method from lens culinaris. AFP-L3
      affinity adsorption microspincolumns which were made from LCA coupled with
      activated Sepharose 4B were prepared. By adding into the centrifuge column, serum
      was absorbed and eluted to purify AFP-L3. The results of purified AFP-L3
      detection of 10 cases AFP positive sera by electro-chemiluminescence immunoassay
      were compared with traditional crossed affinity immunoelectrophoresis. RESULTS: 8
      of 10 cases AFP-L3 concentration were greater than 5 ng/ml in purified sera. Six
      cases show positive reaction in affinity immune cross electrophoresis experiment.
      CONCLUSION: Successfully established purification method of AFP-L3 by affinity
      absorption based on microspincolumn. The method was more conducive to clinical
      laboratory applications due to its high sensitive and easy operation.

PMID- 24044221
TI  - [Construction and expression of non-structural protein gene 3-4b of HCV 1b based
      on the adenoassociated virus vector].
AB  - OBJECTIVE: To clone 1b type of HCV NS3-4b Gene and express in HEK 293 cells, lay
      the foundation for further study of the HCV NS3-4b recombinant adeno-associated
      virus vaccine and its dendritic cell vaccine. METHODS: HCV 1b patients' serum was
      collected, and full length NS3-4b segment was amplified by RT-PCR and cloned into
      adeno-associated virus' expression vector pAAV. CMV. EGFP in order to express in
      HEK 293 cells. At last, it was validated whether express or not by Western Blot.
      RESULTS: The 1b type gene NS3-4b were amplified and consistent to the expected
      size (2838 bp), the recombinant plasmid has been confirmed its successful
      restructured by double enzyme and sequencing, at last, Western Blot map can see
      objective protein expression after it transfect HEK 293 cells. CONCLUSION: The
      adeno-associsted virus recombination HCV NS3-4b plasmid have successfully
      constructed and it can express in eukaryotic cells.

PMID- 24044222
TI  - [Detection of human parvovirus B19, human bocavirus and human parvovirus 4
      infections in blood samples among 95 patients with liver disease in Nanjing by
      nested PCR].
AB  - OBJECTIVE: To analyze the infection of human parvovirus B19, human bocavirus
      (HBoV) and human parvovirus 4 (PARV4) in blood samples among patients with liver
      disease in Nanjing by molecular detection. METHODS: Nested PCR assays were
      designed and validated to detect B19, HBoV and PARV4, respectively. The assays
      were used to screen three parvoviruses in blood samples from 95 patients with
      different liver disease in Nanjing. The parvovirus infection was analyzed
      statistically. RESULTS: The detection limits were 10 copies of genomic DNA
      equivalents per reaction for each assays and the good specificity were observed.
      The frequency of B19 and HBoV were 2/95 (2.1%) and 9/95 (9.5%) in blood samples
      respectively. No PARV4 was detected. HBoV was detected in 3/5 patients with drug
      induced hepatitis. CONCLUSION: Both B19 and HBoV infection were detected in blood
      from patients with liver disease.

PMID- 24044223
TI  - [Preparation and characterization the polyclonal antibody of the nonstructural
      protein of human highly pathogenic H5N1 avian influenza viruses].
AB  - OBJECTIVE: Of this study was to prepare high sensitivity and high specificity of
      highly pathogenic H5N1 subtype avian influenza virus NS1 protein antibody and a
      preliminary assessment of its potency. METHODS: Construct pET-28a (+) recombinant
      vector containing the H5N1 subtype of avian influenza virus NS1 sequences of E.
      coli BL21 (DE3), induced expression of NS1 protein, NS1 recombinant protein was
      obtained by Ni-NTA column purified by affinity chromatography, and SDS-PAGE and
      Western Blot analysis. Purified protein antigen to immunize New Zealand white
      rabbits, obtained rabbit anti-NS1 serum, affinity-purified polyclonal antibodies.
      Using ELISA and Western Blot analysis of purified antibody titer and specificity.
      RESULTS: NS1 fusion protein was highly expressed in a purity of greater than 90%,
      with the fusion protein was used to immunize New Zealand white rabbits anti-NS1
      polyclonal antibody titer of 1:80 000, and specific recognition of the H5N1
      subtype of avian influenza virus NS1 protein. CONCLUSIONS: NS1 polyclonal
      antibodies to NS1 recombinant protein purified antigen, with better potency and
      specificity, and to prepare the conditions for the development of the H5N1
      subtype of avian influenza virus detection kit.

PMID- 24044224
TI  - [Enzyme-linked immunospot test detected specific cellular immune response induced
      by human bocavirus VP2 virus-like particles].
AB  - OBJECTIVE: To discuss the enzyme linked immune spot test (ELISPOT) detected the
      cellular immune response induced by human Bocavirus (HBoV) VP2 virus-like
      particles (VLPs). METHODS: After immunized by HBoV VP2 VLPs, the specific
      cellular immune response in mice were detected by ELISPOT assay, observe the
      ELISPOT results at the conditions of different polypeptide stimulate, different
      cell culture time, different cell concentration and different specific stimulus
      peptide concentration, then screening the right ELISPOT experimental conditions
      and establish the ELISPOT method. RESULTS: The spots induced by HBoV1 VLPs
      immunized mice spleen lymphocytes stimulate with polypeptide P3 (GYIPIENEL) and
      P5 (LYQMPFFLL)were 233 spots/10(6) cells and 157 spots/10(6) cells,spots induced
      by HBoV2 VLPs immunized mice spleen lymphocytes stimulate with polypeptide P8
      (GYIPVIHEL) were 113 spots/10(6) cells; 24 hours is the best time for culture, at
      this time HBoV1 and HBoV2 groups specificity secretion IFN-gamma ratio were 232
      spots/10(6) cells and 119/10(6) cells; Best concentration of mice spleen
      lymphocyte is 5 x 10(5), right now HBoV1 and HBoV2 group specificity secretion
      IFN-gamma ratio were 232 spots/10(6) cells and 108/10(6) cells; Best
      concentration of polypeptides is 10 microg/ml, HBoV1 and HBoV2 group specificity
      secretion IFN -gamma ratio were 233 spots/10(6) cells and 96/10(6) cells.
      CONCLUSIONS: HBoV1 and HBoV2 specificT-cell epitope in BABL/c mice were P3, P5
      (HBoV1) and P8 (HBoV2). The best experiment condition were: cell cultivated for
      24 h, cells concentration for 5 x 10(5) cells/well, stimulating polyperides
      concentration for 10 microg/ml, it can use to study the cellular immune induced
      by HBoV in mice.

PMID- 24044225
TI  - [Establishment and clinical application of TapMan real-time RT-PCR method for
      detection of HHV-6].
AB  - OBJECTIVE: To establish a rapid, sensitive and specific real-time PCR method for
      detection of Human Herpesvirus-6 (HHV-6). METHODS: According to the reference, a
      pair of primers and a probe were designed located in U65-66 gene and to set up
      the standards. We established a real-time RT-PCR method for detection of HHV-6,
      and to verify the specificity, sensitivity, reproducibility. RESULTS: The
      correlation coefficient was 0.999, E = 97.9%, the coefficient of variation values
      of Ct were 0.61% and 3.13% in real-time PCR assay for inter and intra assay,
      respectively. The results of all viruses were negative except of HHV-6 for the
      assay. The quantitative detection limit of the assay was 3 x 10(0) copies/microl.
      CONCLUSION: The real-time PCR assay is highly specific, sensitive and
      reproducible, which can be used to quatitative detecting clinical samples.

PMID- 24044226
TI  - WellPoint takes a hit. Massive medical record breach case to cost insurer $1.7
      million.

PMID- 24044227
TI  - 'The right direction'. Primary-care docs see promise in CMS' proposed pay for non
      face-to-face work.
AB  - The CMS has proposed paying physicians for managing patients apart from face-to
      face office visits. Among the details under consideration are requiring practices
      to use an electronic health-record system that supports access to care, care
      coordination, care management and communications. "It's a step in the right
      direction. The devil will be in the details and, if the burden of documentation
      is so high, people may choose not to spend their time doing it," says Dr. Matt
      Handley, physician and medical director for quality at the Group Health
      Cooperative.

PMID- 24044228
TI  - Who benefits from drug discounts? Drugmakers, hospitals battle over indigent-care
      program.

PMID- 24044229
TI  - Observation care stirs ire. JAMA study says CMS policy hurts hospitals' bottom
      lines.

PMID- 24044230
TI  - Middle of the pack. Co-op plan premiums suggest good long-term prospects.

PMID- 24044231
TI  - Maintaining morale. Hospitals taking steps to counter rising job dissatisfaction.

PMID- 24044232
TI  - Slimming options. Intel adopts narrow network to better manage care.

PMID- 24044233
TI  - Whistle-blower replay. Doc turns to court in kickback case.

PMID- 24044234
TI  - Postponing the reckoning. Employer-based coverage is falling--a fact overlooked
      in latest controversy.

PMID- 24044235
TI  - Win the battle, lose the war? Intergenerational differences among docs may define
      future of healthcare.

PMID- 24044236
TI  - Healthy gains. More physician specialties saw strong pay raises in past year,
      annual compensation survey shows.

PMID- 24044237
TI  - Design by committee. Deadline looms for long-term care proposals.

PMID- 24044238
TI  - Most prescribed pharmaceuticals.

PMID- 24044239
TI  - Frontiers of fertility.

PMID- 24044240
TI  - If you want to do something really big.

PMID- 24044241
TI  - Head case.

PMID- 24044242
TI  - SEIU secures win. But NUHW chief vows to keep focus on Kaiser, may challenge
      results again.

PMID- 24044243
TI  - Retail clinics at tipping point. Pharmacies, chains answering demand for access
      and affordability.
AB  - Retail clinics are booming and the healthcare role of retail pharmacists is
      expanding as consumers and insurers accept the trends. Some say it's a cost
      effective way to deliver care. "lt's a win-win-win scenario. Patient outcomes are
      better, we're getting more prescriptions and, from a payer perspective, their
      total cost of care is lower," says Dr. Jeffrey Kang, chief architect of
      Walgreen's retail expansion.

PMID- 24044244
TI  - Less is more? Fewer choices in state exchanges than expected.

PMID- 24044245
TI  - Zimmer's legal challenge. Devicemaker faces massive liability case over knee
      replacement systems.

PMID- 24044246
TI  - Metrics debated. Rural hospitals defend mortality rates.

PMID- 24044247
TI  - Narrow negotiations. Hospitals fear disruptions from limited networks.

PMID- 24044248
TI  - Guiding elderly care. Group calls for integrated care, communication.

PMID- 24044249
TI  - Highmark closes the deal. Regulators will closely watch to see if insurer keeps
      promises on West Penn.

PMID- 24044250
TI  - Not big on rules. Experienced physicians turned off by intrusive intervention.

PMID- 24044251
TI  - Target providers' sense of entitlement. Americans are paying more for Medicare,
      but where is that money going?

PMID- 24044252
TI  - A model for reform. Medicare must be changed to survive; part D offers a
      solution.

PMID- 24044253
TI  - No small achievement. Rural providers show size isn't barrier to IT success.

PMID- 24044254
TI  - Largest behavioral health providers. Ranked by total revenue in 2011, based on
      CMS Hospital Cost Report data.

PMID- 24044255
TI  - More pain for painkillers.

PMID- 24044256
TI  - [Continuing education, a new entity for health professionals].

PMID- 24044257
TI  - [Nursing specialties and career plans].

PMID- 24044258
TI  - [Register for work].

PMID- 24044259
TI  - 'Friends and family' test: Do you wish they were here?

PMID- 24044260
TI  - A new commission can clean up the NHS.

PMID- 24044261
TI  - Transforming the NHS through its underused estate.

PMID- 24044262
TI  - Make commissioning democratic.

PMID- 24044263
TI  - Acute care: Junior doctors are innovation leaders.

PMID- 24044264
TI  - Integrated care: Come together, right now.

PMID- 24044265
TI  - Patient experience: Put individuals at the centre of care.

PMID- 24044266
TI  - Commissioning support: A meeting of expert minds.

PMID- 24044267
TI  - Pensions: Provide the full picture.

PMID- 24044268
TI  - A model for rapid service change. The NHS must choose to transform itself.

PMID- 24044269
TI  - The bumpy road to healthcare regulation.

PMID- 24044270
TI  - Ethics. Moral guidance.

PMID- 24044271
TI  - Surefire proof that prevention is better than cure.

PMID- 24044272
TI  - Patient experience. Knowledge is empowering.

PMID- 24044273
TI  - Information governance. The price of data sharing.

PMID- 24044274
TI  - Commissioning. Joined up thinking.

PMID- 24044275
TI  - Third sector. A good type of charity case.

PMID- 24044276
TI  - Integrated care. Power to the people.

PMID- 24044277
TI  - [From Gurdon to Yamanaka--a brief history of cell reprogramming].
AB  - This paper describes the genesis of discoveries that have allowed cell
      reprogramming and derivation of induced pluripotent stem cells. This achievement
      has been distinguished by the 2012 Nobel Prize in Physiology or Medicine awarded
      to John B. Gurdon and Shinya Yamanaka. The verdict of the Nobel Committee was as
      follows: "for the discovery that mature cells can be reprogrammed to become
      pluripotent". The basis for the discovery was done by Gurdon in the 60s of the
      twentieth century, although he was not a pioneer in his field of research. The
      last word was pronounced, however, by Yamanaka at the beginning of the twenty
      first century. The Japanese was born fifty years ago, that is exactly the year
      when Gurdon made his most important discoveries. Despite such a large difference
      in age of the two scientists their studies complement each other perfectly and
      promise numerous applications in regenerative medicine.

PMID- 24044278
TI  - [The first developmental decisions--cell differentiation in preimplantation mouse
      embryo].
AB  - The question, how multicellular fetus emerges from a totipotent single cell, the
      zygote, raises ceaseless curiosity of researchers. During embryogenesis, the
      cells of the embryo gradually lose their full developmental potency and begin to
      differentiate. The initial period of embryonic development of mammals, including
      the mouse, is primarily devoted to cell commitment of the pluripotent lineage
      that will give rise to all of the tissues of the embryo proper, as well as to the
      formation of extraembryonic tissues essential for embryo survival within the
      mother's uterus. The milestone in the studies of early stages of embryogenesis
      was derivation and maintenance of in vitro cultured stem cells that mimic the
      identity and properties of the primary cell lineages. It made possible to explore
      the mechanisms responsible for the critical early cell fate decisions taking
      place in vivo within the embryo.

PMID- 24044279
TI  - [The alchemy--epigenetic regulation of pluripotency].
AB  - Embryonic stem cells (ESCs) self renew their population, also they are
      pluripotent which means they can differentiate into any given cell type. In
      specific culture conditions they remain undifferentiated. On the cellular level
      pluripotency is determined by many transcription factors, e.g. Sox2, Nanog, Klf4,
      Oct4. Epigenetic regulation is also crucial for both self renewal and
      pluripotency. This review focuses on epigenetic mechanisms, among them DNA
      methylation, posttranslational histone modifications, ATP dependent chromatin
      remodeling and miRNAs interactions. These mechanisms affect embryonic stem cells
      functions keeping them poised for differentiation.

PMID- 24044280
TI  - [Roles of microRNA in cell reprogramming].
AB  - Reprogramming of somatic cells with defined transcription factors which leads to
      the acquisition of pluripotent phenotype requires many modifications in gene
      expression profile, metabolism and chromatin structure. MicroRNAs, a short non
      coding RNA that inhibit translation of recognized mRNA sequences play an
      important role in this process. Because of the pleiotropism of their action
      microRNAs regulate subsequent steps in cellular reprogramming, among others
      activation of p53, mesenchymal-to-epithelial transition and development of
      embryonic gene expression profile. Further studies on the function of microRNA in
      reprogramming can increase our understandbing of generation, maintenance and
      differentiation of induced pluripotent stem cells.

PMID- 24044281
TI  - [Why do we need induced pluripotent stem cells in neurobiology?].
AB  - Reprogramming of somatic cells made possible to study in vitro inaccessible human
      cells, such as different types of neurons. Almost immediate consequence of the
      emergence of this technology was the development of a number of cellular models
      of the nervous system diseases. They are used both to explore the cellular
      mechanisms of these diseases and for the development of new pharmacological
      strategies. Reprogrammed cells are also a potential alternative to embryonic stem
      cells for transplantation. This article presents the most important achievements
      in the use of cell reprogramming technology in neurobiology and at the same time
      points out the limitations of the methodology and the expected directions of its
      development.

PMID- 24044282
TI  - [Bioengineering of neural stem cell niche].
AB  - Maintenance of developmental and regenerative capability of the tissue highly
      depends upon mutual interaction of the stem cells with the components of their
      microenvironment (niche). The nature of this interaction is determined by the
      biochemical and biophysical properties of the niche constituencies. Although
      knowledge about the components of the stem cell microenvironment and their
      architecture is growing quickly, we still need to unravel the mechanisms
      underlying the control of the niche functioning, enabling stem cells
      differentiation and homeostasis of the tissue. Advancement in biotechnology
      provides tools to build up in vitro "biomimetic" microenvironments resembling a
      natural stem cell niche, where the cell is provided with diverse extracellular
      signals exerted by soluble and structural cues, mimicking those found in vivo. To
      obtain such microenvironment in vitro emerging nano/biotechnology methods were
      applied, using biomaterials of new generation, which enable controlling of the
      stem cell differentiation by time and special related release of the active
      factors. This article is providing an overview of the new research strategies for
      the bioengineering of the stem cell niche and gives the examples of the
      cell/biomaterial 2D and 3D complex systems used for basic and preclinical
      research as well as entering clinical applications for the therapy of the nervous
      system.

PMID- 24044283
TI  - [Mesenchymal stem cells].
AB  - The multipotential progenitor cells called ,Mesenchymal Stem Cells" (MSC) are
      capable of differrentiation at least into bone, cartilage, and adipose tissues.
      The commonly recognized role of these cells is the formation of connective tissue
      which participates in formation of every organ. The progeny of MSC produces also
      the hematopoietic microenvironment, recently it have been documented that these
      cells are capable of the modulation of the immune system activities. MSC are
      isolated from the tissues of fetal origin (umbilical cord, cord blood, or
      placenta), or from several adult donor sites, in particular from bone marrow and
      adipose tissue which are most useful for practical purposes. The capability of
      multipotential differentiation, immunomodulation, and the regulation of the
      endogenous tissue repair are the reasons why mesenchymal stem cells are widely
      applied for regenerative medicine purposes.

PMID- 24044284
TI  - [Translational research in regenerative medicine: an example of bone marrow
      transplantation].
AB  - Science provides diagnostic and therapeutic methods that subsequently need to be
      introduced to routine clinical practice in ordered way. Translational research
      allows for adaptation of methods developed on experimental animals to the
      requirements of man. This process requires on one hand consideration of
      biological differences between model organisms (in case of bone marrow
      transplantation mainly mouse and dog) and man and consideration of differences in
      size (usually upscaling of procedures). Procedures that have been elaborated
      during translation of methods of transplantation of hematopoietic cells
      elaborated on experimental animals to clinical situations could be successfully
      used during introduction to the clinic of other types of cellular therapies.

PMID- 24044285
TI  - [Are satellite cells stem cells?].
AB  - Satellite cells, localized in the niche between the membrane of muscle fiber and
      basal lamina that surrounds it, serve as a source of myoblasts that are necessary
      for both growth and regeneration of skeletal muscle. Apart from their ability to
      convert into myoblasts, satellite cells are also able to self-renew, thus, they
      meet requirements for tissue specific, unipotent stem cells. Recently conducted
      research revealed that population of satellite cells is heterogeneous. The
      article summarizes current information on biology and characteristics of
      satellite cells, and also describes models concerning mechanisms of self-renewal
      and differentiation of satellite cells. Experiments regarding in vitro
      differentiation of satellite cells into other cell types are also discussed.
      Moreover, other population of stem cells localized in the muscle are described in
      this review.

PMID- 24044286
TI  - [Epidermal stem cells--biology and potential applications in regenerative
      medicine].
AB  - Stem cells are involved in the renewal and regeneration of the epithelium of
      various organs. The largest reservoir of epithelial stem cells in the human body
      is the skin. This organ is a specialized interior barrier protecting the body
      from the influence of physical, chemical and biological factors, ensuring at the
      same time the reception of signals from the external environment. Skin is also
      involved in numerous physiological processes which determine the homeostasis of
      the body. Renewal and regeneration of the epidermis which is the outer layer of
      the skin, is possible by the presence of different populations of stem cells that
      reside in microenvironments (niches), that creates specific conditions to
      preserve the biological properties of these cells. Because divisions of cells in
      niches are quite rare, it became possible to distinguish them from other rapidly
      proliferating cells of the skin. On this basis, the stem cells in the
      interfollicular epidermis, bulge region of the hair follicles, and within the
      sebaceous glands were located. Moreover hair follicles are suggested to be a
      niche for melanocyte progenitor cells and other multipotent stem cells derived
      from the neural crest, as well as mesenchymal stem cells. The presence of stem
      cells that are characterized by high proliferative potential and the ability to
      self-renew allow maintaing homeostasis and regeneration of epidermis.
      Identification, isolation and characterization of epithelial stem cells is
      necessary to understand skin diseases background, develop effective methods for
      their treatment and for wider use of stem cells in regenerative medicine, gene
      therapy or cosmetology.

PMID- 24044287
TI  - [Biomaterials engineering strategies for spinal cord regeneration: state of the
      art].
AB  - Traumatic spinal cord injuries are very serious burden for the organism of
      affected human population, and are more critical because mostly touching the
      young cluster of population. Physical, emotional and economic problems caused by
      traumatic spinal cord injuries as a general rule significantly limit the
      individual patient functionality and are burden for the society. The spinal cord
      has considerable lack of ability for spontaneous and functional regeneration,
      hence the spinal cord injury cause a solemn and frequently permanent
      disabilities. The pathophysiology of spinal cord injury is the results of
      sequential two phenomena, primary physical and biochemical secondary mechanisms
      of injury. After physical injury, the spinal cord undergoes a sequential
      progression in biochemical pathologic deviations increasing after injury, that
      are mutually deteriorating and cause further damage in the spinal cord.
      Consequently series of pathological processes lead to haemorrhage, oedema,
      neuronal necrosis, axonal fragmentation, demyelination of the remaining axons,
      and formation of ultimately cyst. Furthermore spinal cord injuries can
      immediately result in neural cells death and cause disruption of the blood supply
      to the site of the injury. The most important difference between peripheral and
      central nervous system is the fact that in the spinal cord the neuronal cell
      bodies are damaged, while in the peripheral nervous system only axons are
      injured. In the surroundings of the spinal cord, one of the major factors
      hampering regeneration is the glial scar expansion. The spreading of densely
      packed astrocytes on the site of injuries effectively inhibit axon growth through
      the nerve grow blocking. Glial scar, which consists mainly of overactive
      astrocytes and fibroblasts, as well as the presence of growth-inhibitor molecules
      such as chondroitin sulphate proteoglycans (derived from the breakdown of damaged
      nerve cells) form a physicochemical barrier for effective regenerating axons. The
      recent scientific progress in medicine, biology and biomaterials engineering, and
      predominantly in the fields of neurosurgery, cell culture and tissue engineering,
      creates the opportunity for the development of new therapies, which support
      healing of the effects of traumatic spinal cord injuries and prevent further
      neurodegenerative processes. The most promising effects so far have been obtained
      using well-designed polymer scaffold as structural support for axon regeneration
      combined with drug delivery system or therapeutic cell line and neurotrophic
      factors. This review article focuses on the application of selected biomaterials
      for the regeneration of traumatic spinal cord injuries. First, the basic
      anatomical structure of the spinal cord has been described. Then the injury and
      neurodegenerative mechanisms within the peripheral and central nervous system
      have been compared. The pathophysiology of the spinal cord damage has been
      referred to the current strategy of biomaterials engineering in experimental
      therapies supporting neuroregeneration processes. In the summary, the promising
      interdisciplinary therapeutic strategies aimed at the regeneration of the spinal
      cord have been highlighted.

PMID- 24044288
TI  - [Examination of influence of microstructure of grafts on TiO2 base on the process
      of bone tissue forming].
AB  - AIM OF THE STUDY: Evaluation of the influence of the introduced structure
      modification in porous ceramic grafts on TiO2 base on overgrowing with bone
      tissue, in examinations with use of scanning microscopy and X-rays was the
      subject of the examinations. MATERIAL AND METHOD: New ceramic materials based on
      TiO2 with high values of mechanical resistance, large sintering degree and
      biocompatibility in in vitro conditions were prepared. Those properties cause
      that they are worth interest as potential osteosubstitutive materials. Two kinds
      of grafts were created from ceramics based on TiO2: with compact and porous
      structure. The introduced structure modification - macroporosity - had the
      purpose to give osteoconductive properties to the grafts, to evoke processes
      favorable for bone tissue forming. In examinations of the local reaction of bone
      tissue after implantation of the formed porous grafts, degree of their
      osteointegration, the essential issue is the evaluation of the settling of the
      inner spaces with supporting tissues. Samples of the tested compact and porous
      materials in the form of cylinders were implanted in femoral bones of rabbits for
      a period till 6 months. The surfaces of grafts and the degree of their settling
      with supporting tissues were evaluated in cross-sections of the implants with
      light and scanning microscopic methods and they were confirmed in X-ray tests.
      RESULTS: Analysis of the obtained data showed that, the surface of solid ceramic
      on TiO2 base was covered mainly with increasing with a time of observation
      quantities of extracellular substance and lamellas of bone. The macrporous
      structure of porous ceramic on TiO2 base enabled settling of the inner spaces of
      graft with supporting tissue cells, partly in the 1st month, more intensively in
      the 3rd and it was not completed in the 6th month after implantation.
      CONCLUSIONS: Porous grafts in the form of ceramic foam on TiO2 base showed
      osteoconductive properties, though process of colonization after 6th month
      observation was not completed and the condition of the cells inside of the
      implant was reduced.

PMID- 24044289
TI  - [Network form of the Kedem-Katchalsky equations for ternary non-electrolyte
      solutions. 1. Evaluation of Rij Peusner's coefficients for polymeric membrane].
AB  - INTRODUCTION: Peusner's network thermodynamics (PNT) enables symmetrical or
      hybrid transformation of membrane transport equations. For Kedem-Katchalsky
      equations (K-K) these transformations create the network form of these equations
      that contain new types of coefficients which can be calculated from the
      experimentally determined transport parameters, such as hydraulic permeability
      coefficient (Lp), solute permeability (omega) and reflection (sigma). For ternary
      and homogeneous solutions of non-electrolytes, transformations result in two
      symmetrical and six hybrid K-K network equations. The symmetrical forms of K-K
      network equations contain Peusner's coefficients Rij or Lij, whereas hybrid forms
      of K-K network equations contain Peusner's coefficients Hij, Nij, Kij, Pij, Sij
      or Wij. PURPOSE: Derivation of network form of KK equations for homogeneous
      ternary solutions that contain nonelectrolytes Peusnera ratios Rij (i, j element
      of {1, 2, 3}) presented in the third-order matrix [R]. Evaluation of transport
      properties of the membrane using Peusner's coefficients Rij, the determinant of
      the matrix [R], somber elements belonging to Rij, quotients Rij/det [R] and
      quotients det [Rij]/det [R]. MATERIALS AND METHODS: A cellulose acetate
      hemodialysis membrane (Nephrophan) of known parameters for transport of aqueous
      glucose and ethanol solutions of was a research material. The PNT formalism and K
      K equation for ternary nonelectrolyte solutions were a research tool in this
      paper. RESULTS: The network form of K-K equations for ternary solutions was
      presented, that was obtained using the symmetric transformation of Peusner's
      thermodynamic networks. The resulting equations were used to interpret the
      transport of nonelectrolytes solutions consisting of solvent and two solutes. We
      calculated dependences of Peusner's coefficients Rij (i, j element of { 1, 2, 3})
      and det [R] from the average concentration of one component of solution in the
      membrane (C1) with a constant value of a second component (C2) in conditions of
      solutions homogeneity. We also calculated dependencies of minors belonging to the
      elements Rij, the quotients Rij/det [R] and quotients det [Rij]/det [R] on the
      average concentration of one component of solution in the membrane (C1) at a
      constant value of the second component (C2). CONCLUSION: Network form of K-K
      equations containing Peusner's coefficients Rij (i, j element of {1, 2, 3}) is a
      novel tool suitable for the examination of the membrane transport. The presented
      calculations showed that the values of coefficients R11, R21, R22, R23 and R13
      are sensitive to the composition and concentration of the solutions separated by
      a polymer membrane.

PMID- 24044290
TI  - [Network form of the Kedem-Katchalsky equations for ternary non-electrolyte
      solutions. 2. Evaluation of Lij Peusner's coefficients for polymeric membrane].
AB  - INTRODUCTION: Symmetrical or hybrid transformation of Kedem-Katchalsky membrane
      transport equations (K-K) can be performed using Peusner's network thermodynamics
      (PNT). For ternary and homogeneous solutions of non-electrolytes it result in two
      symmetrical and six hybrid network form of K-K equations. The symmetrical form of
      these equations contain Peusner's coefficients Rij or Lij, and hybrid form-
      Peusner's coefficients Hij, Nij, Kij, Pij, Sij or Wij. PURPOSE: Derivation of
      network form of K-K equations for homogeneous ternary non-electrolyte solutions
      containing Peusner's coefficients Lij (i, j element of {1, 2, 3}) creating a the
      third- order matrix of Peusner's coefficients [L] and the calculation of the
      Peusner's coefficients Lij and comparison these coefficients with coefficient Rij
      presented in the first part of the paper (Polim. Med.). MATERIALS AND METHODS: A
      cellulose acetate hemodialysis membrane (Nephrophan) with known parameters for
      the transport of aqueous solutions of glucose and ethanol was a research
      material. Our research method was the PNT formalism and K-K equation for ternary
      non-electrolyte solutions. RESULTS: The network form of K-K equations for ternary
      solution consisting of solvent and two dissolved substances was obtained.
      Dependences of Peusner's coefficients Lij (i, j element of {1, 2, 3}) on the
      average concentration of one component of solution in the membrane (C1) with a
      constant value of second component (C1) were calculated in the conditions of
      solution homogeneity. These coefficients can be calculated on the basis of based
      on experimentally determined transport parameters i.e. the hydraulic permeability
      coefficients (Lp), solute permeability (omega) and reflection (sigma).
      CONCLUSION: Network form of K-K equations containing Peusner's coefficients Lij
      (i, j element of {1, 2, 3}) can be used for examination of the membrane
      transport. The calculations showed that only coefficients L12, L22, L23 i L32 are
      sensitive to the concentration and composition of the solutions separated by the
      polymer membrane.

PMID- 24044291
TI  - [Network form of the Kedem-Katchalsky equations for ternary non-electrolyte
      solutions. 3. Evaluation of Hij Peusner's coefficients for polymeric membrane].
AB  - INTRODUCTION: Using symmetrical or hybrid transformation Kedem-Katchalsky
      membrane transport equations (K-K) for ternary solutions can be transformed to
      symmetrical (Rij lub Lij) or hybrid (contain coefficients Hij, Wij, Sij, Nij, Kij
      or Pij) network form. PURPOSE: Derivation of network form of K-K equations for
      homogeneous ternary non-electrolyte solutions containing Peusner's coefficients
      Hij (i, j element of {1, 2, 3}) and calculation of these coefficients for
      solutions consisting of solvent and two dissolved substances. Moreover comparison
      of these coefficients with coefficients Rij and Lij presented in the first and
      second part of the paper (Polim. Med.) was shown. Coefficients Hij (i, j element
      of {1, 2, 3}) can be calculated on the basis of experimentally determined
      transport parameters i.e. the hydraulic permeability coefficients (Lp), solute
      permeability (omega) and reflection (sigma). MATERIALS AND METHODS: The research
      material was the membrane (Nephrophan) with known parameters for the transport of
      aqueous solutions of glucose and ethanol and the research tool was the formalism
      of Peusner's network thermodynamics (PNT) and K-K equation for ternary non
      electrolyte solutions. RESULTS: Using the hybrid transformation of the Peusner's
      thermodynamic networks, the network form of K-K equations for ternary solution
      consisting of solvent and two dissolved substances was presented. Dependences of
      Peusner's coefficients Hij (i, j element of {1, 2, 3}) in the conditions of
      solutions homogeneity from the average concentration of one component of solution
      in the membrane (C1) with a constant value of second component (C2). CONCLUSION:
      Analysis of Peusner's coefficients Hij (i, j element of {1, 2, 3}) is a new tool,
      which can be used for examination of the membrane transport. The calculations
      proved, that the values of coefficients H12, H21, H22 and H32 are sensitive to
      the concentration and composition of the non-electrolyte solutions separated by
      the polymer membrane.

PMID- 24044292
TI  - The dangerous Sopranos diet.

PMID- 24044293
TI  - Working to keep reform on track. A changing industry poses challenges for
      healthcare leaders across all sectors.
AB  - Everyone on the 100 Most Influential People in Healthcare ranking for 2013 plays
      some part in the massive change roiling the U.S. healthcare system. Providers,
      payers, regulators, politicians and advocates all grapple daily with how reform
      is affecting their jobs and organizations. Aetna CEO Mark Bertolini, calls it
      necessary. "I truly believe we have a once-in-a-lifetime opportunity to improve
      quality, and control costs and make healthcare work for everyone," says
      Bertolini, the No. 6 ranked official on this years list.

PMID- 24044294
TI  - 'Death by a thousand cuts' Hospital execs say Medicaid expansion needed.

PMID- 24044295
TI  - Reducing wasteful care. Results of 'choosing wisely' among docs questioned.

PMID- 24044296
TI  - The case of the disappearing subsidies. Lower-than-expected premiums push down
      ACA subsidies in some states.

PMID- 24044297
TI  - Scaling back. Some employers altering health plans in reaction to ACA, rising
      costs.

PMID- 24044298
TI  - Culture, costs, quality. Top 25 women honorees on healthcare hot topics.

PMID- 24044299
TI  - The IPAB punching bag. New Mass. cost-control panel could provide ammunition for
      its defenders.

PMID- 24044300
TI  - Support for diabetics. Health workers aid overstretched docs by helping patients
      manage disease.

PMID- 24044302
TI  - Insuring market growth. Execs at large health insurers pursue innovation as
      reform rolls out.

PMID- 24044301
TI  - Lobbying for change. Leaders of trade groups, associations work to spread their
      influence.

PMID- 24044303
TI  - Votes of approval, disapproval. Officials on list represent the full political
      spectrum.

PMID- 24044304
TI  - Shared influence. Provider organizations team up through affiliations.

PMID- 24044305
TI  - More docs get EHR help. Medical scribes move beyond the emergency room.

PMID- 24044306
TI  - Major hospitalist service contractors.

PMID- 24044307
TI  - Shake it up. Schools are subbing smoothies for fruit. Is that good for kids?

PMID- 24044308
TI  - Service reconfiguration: Has the NHS lost the ability to deliver major service
      change?

PMID- 24044309
TI  - A solution to failure or a sticking plaster?

PMID- 24044310
TI  - Why NHS leaders should heed Gandhi's message.

PMID- 24044312
TI  - Workforce: 'It's easier than people believe'.

PMID- 24044311
TI  - The finance regime after Francis.

PMID- 24044313
TI  - Workforce: case studies. It's not just about courses.

PMID- 24044314
TI  - Wise up to social media pitfalls.

PMID- 24044315
TI  - International innovators: part 2 of 3. Shining a light on coordinated care.

PMID- 24044316
TI  - Books: Seize the moment when opportunity comes knocking.

PMID- 24044317
TI  - Procurement: CCGs hit the ground running.

PMID- 24044318
TI  - Clinical leaders: Listening is the key to better care.

PMID- 24044319
TI  - Acute care: The NHS needs to act now on the warning signs in emergency care.

PMID- 24044320
TI  - Thatcher ducked a fight--now we must face it.

PMID- 24044321
TI  - Monitor is keeping us in the dark.

PMID- 24044322
TI  - Reconfiguration: Can mergers solve acute care problems in NHS?

PMID- 24044323
TI  - International innovators: part 3 of 3. A grand vision for social eyecare.

PMID- 24044324
TI  - Patient experience: A faster pathway from A to B for hepatitis C.

PMID- 24044325
TI  - Governance: Transforming the culture in the NHS.

PMID- 24044326
TI  - Interview: Make all staff part of the solution.

PMID- 24044327
TI  - E-cigarette use penalized. Some employers imposing tobacco-use fees.

PMID- 24044328
TI  - Strategic move. With IPO, Premier targets data analytics game plan.

PMID- 24044329
TI  - In Michigan's wake. After long battle, expansion spotlight shifts.

PMID- 24044331
TI  - New sales challenge. As Oct 1 nears, insurers market to consumers.

PMID- 24044330
TI  - Selling health exchanges. States launch ad campaigns to promote online
      marketplaces.

PMID- 24044332
TI  - Filling a need. Some want to expand role of dental hygienists.

PMID- 24044333
TI  - Nursing challenges. DeMoro talks patient care, ACA.

PMID- 24044334
TI  - Medicaid expansion's tax implications. Opponents should consider fairest way to
      pay for healthcare.

PMID- 24044335
TI  - Letting the sunshine in. CMS rolls out tools to make physician payments program
      work.

PMID- 24044336
TI  - An inside job? Outsourcing--clinical and nonclinical--remains a popular option
      for supply chain managers, but some systems are bringing services in-house.

PMID- 24044337
TI  - Consulting on costs, quality. Physicians, other providers enlisted to help steer
      patients toward savings.

PMID- 24044338
TI  - Largest healthcare management consulting firms.

PMID- 24044339
TI  - Use MAPS to prevent prescription drug abuse in your practice.

PMID- 24044340
TI  - Opioid use on the rise: is the pen mightier than the alternatives when it comes
      to chronic pain management?

PMID- 24044341
TI  - Community-based training helps solve physician shortage. Community residencies
      offer new medical training models.

PMID- 24044342
TI  - A window of opportunity--how organized medicine led an anesthesiologist to the
      state senate.

PMID- 24044343
TI  - Meaningful use and public health reporting.

PMID- 24044344
TI  - No-show new patients may leave physicians at risk.

PMID- 24044345
TI  - Skin in the game: how Kay Watnick, MD, used MSMS to turn her passion Into law.

PMID- 24044346
TI  - Does your team of professionals lack coordination?

PMID- 24044347
TI  - Hepatitis B: opportunities to reduce rate of infection.

PMID- 24044348
TI  - Looking after yourself is just as important as caring for your patients.

PMID- 24044349
TI  - Prescription drug abuse--yes, it is our problem.

PMID- 24044350
TI  - Controlled radical polymerization and quantification of solid state electrical
      conductivities of macromolecules bearing pendant stable radical groups.
AB  - Macromolecules with aliphatic backbones that bear pendant stable radical groups
      (i.e., radical polymers) have attracted much attention in applications where a
      supporting electrolyte is capable of aiding charge transport in solution;
      however, the utilization of these materials in solid state applications has been
      limited. Here, we synthesize a model radical polymer, poly(2,2,6,6
      tetramethylpiperidinyloxy methacrylate) (PTMA), through a controlled reversible
      addition-fragmentation chain transfer (RAFT) mediated polymerization mechanism to
      generate well-defined and easily-tunable functional polymers. These completely
      amorphous, electronically-active polymers demonstrate relatively high glass
      transition temperatures (Tg ~170  degrees C) and, because of the aliphatic nature
      of the backbone of the radical polymers, are almost completely transparent in the
      visible region of the electromagnetic spectrum. Additionally, we quantify the
      conductivity of PTMA (~1*10(-6) S cm(-1)) and find it to be on par with pristine
      pi-conjugated polymers such as poly(phenylene vinylenes) (PPVs) and poly(3
      alkylthiophenes) (P3ATs). Furthermore, we demonstrate that the addition of small
      molecules bearing stable radical groups provides for more solid state charge
      hopping sites without altering the chemical nature of radical polymers; this, in
      turn, allows for an increase in the conductivity of PTMA relative to neat PTMA
      thin films while still retaining the same high degree of optical transparency and
      device stability. Because of the synthetic flexibility and easily-controlled
      doping mechanisms (that do not alter the PTMA chemistry), radical polymers
      present themselves as promising and tunable materials for transparent solid-state
      plastic electronic applications.

PMID- 24044351
TI  - Three-dimensional {Co(3+)-Zn2+} and {Co(3+)-Cd2+} networks originated from
      carboxylate-rich building blocks: syntheses, structures, and heterogeneous
      catalysis.
AB  - The present work shows the utilization of Co(3+) complexes appended with either
      para- or meta-arylcarboxylic acid groups as the molecular building blocks for the
      construction of three-dimensional {Co(3+)-Zn(2+)} and {Co(3+)-Cd(2+)}
      heterobimetallic networks. The structural characterizations of these networks
      show several interesting features including well-defined pores and channels.
      These networks function as heterogeneous and reusable catalysts for the regio-
      and stereoselective ring-opening reactions of various epoxides and size-selective
      cyanation reactions of assorted aldehydes. 

PMID- 24044353
TI  - Antioxidant signal and kidney injury molecule-1 levels in shockwave lithotripsy
      induced kidney injury.
AB  - PURPOSE: Shockwave lithotripsy (SWL) induces acute kidney injury (AKI) that
      extends from the papilla to the outer cortex by causing ischemia and the
      production of nephrotoxic agents. Direct ischemic damage and the generation of
      free radicals cause injury to the proximal tubular cells. Kidney injury molecule
      1 (KIM-1) is a transmembrane glycoprotein that is upregulated in proximal tubular
      cells after ischemic or nephrotoxic injury and is not expressed in healthy
      kidneys. We evaluated the extent of free radical production in response to SWL by
      measuring urinary total antioxidant capacity (TAC) and total oxidant status
      (TOS). Furthermore, we investigated the severity of SWL-induced kidney injury by
      measuring KIM-1 expression levels. PATIENTS AND METHODS: The study population
      comprised 30 patients who were carefully selected and 30 age and sex matched
      control subjects. All patients received the same SWL procedure. Midstream urine
      samples were collected from patients before SWL and at 120 minutes after SWL.
      Urine KIM-1 levels were measured by enzyme-linked immunosorbent assay, and TAC
      and TOS were measured via spectrophotometry. RESULTS: Mean levels of TAC (2.88+/
      0.56 mmolTxEq/L),TOS (8.27+/-1.57 MUmolH2O2Eq/L), and KIM-1 (0.55+/-0.08 ng/mL)
      before SWL were not significantly different from mean TAC, TOS, and KIM-1 levels
      measured from the control group at 2.81+/-0.42 mmolTxEq/L, 10.73+/-1.4
      MUmolH2O2Eq/L, and 0.51+/-0.07 ng/mL, respectively. Two hours after SWL, mean
      urine TAC levels (2.81+/-0.85 mmolTxEq/L, P=0.02) were decreased and mean KIM-1
      expression (0.85+/-0.11 ng/mL, P=0.01) was significantly increased, but there was
      no significant difference in mean TOS levels (11.24+/-1.9 MUmolH2O2Eq/L, P=0.627)
      compared with the control group. CONCLUSIONS: The increased burden of free
      radical oxidants in the setting of decreasing antioxidant capacity may be one of
      the initial indicators of AKI after SWL. Moreover, KIM-1 demonstrates great
      potential as an early and noninvasive biomarker of SWL-induced kidney injury.

PMID- 24044352
TI  - Probing heme delivery processes in cytochrome c biogenesis System I.
AB  - Cytochromes c comprise a diverse and widespread family of proteins containing
      covalently bound heme that are central to the life of most organisms. In many
      bacteria and in certain mitochondria, the synthesis of cytochromes c is performed
      by a complex post-translational modification apparatus called System I (or
      cytochrome c maturation, Ccm, system). In Escherichia coli , there are eight
      maturation proteins, several of which are involved in heme handling, but the
      mechanism of heme transfer from one protein to the next is not known. Attachment
      of the heme to the apocytochrome occurs via a novel covalent bond to a histidine
      residue of the heme chaperone CcmE. The discovery of a variant maturation system
      (System I*) has provided a new tool for studying cytochrome c assembly because
      the variant CcmE functions via a cysteine residue in the place of the histidine
      of System I. In this work, we use site-directed mutagenesis on both maturation
      systems to probe the function of the individual component proteins as well as
      their concerted action in transferring heme to the cytochrome c substrate. The
      roles of CcmA, CcmC, CcmE, and CcmF in the heme delivery process are compared
      between Systems I and I*. We show that a previously proposed quinone-binding site
      on CcmF is not essential for either system. Significant differences in the heme
      chemistry involved in the formation of cytochromes c in the variant system add
      new pieces to the cytochrome c biogenesis puzzle. 

PMID- 24044354
TI  - A general method for making peptide therapeutics resistant to serine protease
      degradation: application to dipeptidyl peptidase IV substrates.
AB  - Bioactive peptides have evolved to optimally fulfill specific biological
      functions, a fact which has long attracted attention for their use as therapeutic
      agents. While there have been some recent commercial successes fostered in part
      by advances in large-scale peptide synthesis, development of peptides as
      therapeutic agents has been significantly impeded by their inherent
      susceptibility to protease degradation in the bloodstream. Here we report that
      incorporation of specially designed amino acid analogues at the P1' position,
      directly C-terminal of the enzyme cleavage site, renders peptides, including
      glucagon-like peptide-1 (7-36) amide (GLP-1) and six other examples, highly
      resistant to serine protease degradation without significant alteration of their
      biological activity. We demonstrate the applicability of the method to a variety
      of proteases, including dipeptidyl peptidase IV (DPP IV), dipeptidyl peptidase 8
      (DPP8), fibroblast activation protein alpha (FAPalpha), alpha-lytic protease
      (alphaLP), trypsin, and chymotrypsin. In summary, the "P1' modification"
      represents a simple, general, and highly adaptable method of generating
      enzymatically stable peptide-based therapeutics. 

PMID- 24044356
TI  - Simulation of the amide I infrared spectrum in photoinduced peptide
      folding/unfolding transitions.
AB  - The amide I' infrared spectrum of a alpha-helical photoswitchable peptide is
      calculated here by means of a mixed quantum mechanics/molecular dynamics
      theoretical-computational methodology based on the perturbed matrix method (PMM).
      The contribution of specific residues to the total spectrum is also analyzed and
      the results compared to previous experimental spectroscopic data, obtained by
      means of site-specific isotope labeling at different residues, resulting in good
      agreement. One of the residues (Ala7) shows atypical spectroscopic behavior in
      both the experimental and calculated spectra, i.e., the folded-state amide I'
      band is shifted to higher frequencies than the unfolded-state one, while the
      other residues show the opposite behavior. The calculations reveal the origin of
      this uncommon spectroscopic trend and point to a crucial role of the molecular
      switch, the presence of which perturbs the conformational sampling of the
      peptide. Indeed, infrared spectra of the same peptide calculated in the absence
      of the molecular switch show that the single-residue spectrum of Ala7 does not
      have any distinguishing feature, resembling the spectra of the other analyzed
      residues. 

PMID- 24044355
TI  - Oligomerization and Ca2+/calmodulin control binding of the ER Ca2+-sensors STIM1
      and STIM2 to plasma membrane lipids.
AB  - Ca2+ (calcium) homoeostasis and signalling rely on physical contacts between Ca2+
      sensors in the ER (endoplasmic reticulum) and Ca2+ channels in the PM (plasma
      membrane). STIM1 (stromal interaction molecule 1) and STIM2 Ca2+ sensors
      oligomerize upon Ca2+ depletion in the ER lumen, contact phosphoinositides at the
      PM via their cytosolic lysine (K)-rich domains, and activate Ca2+ channels.
      Differential sensitivities of STIM1 and STIM2 towards ER luminal Ca2+ have been
      studied but responses towards elevated cytosolic Ca2+ concentration and the
      mechanism of lipid binding remain unclear. We found that tetramerization of the
      STIM1 K-rich domain is necessary for efficient binding to PI(4,5)P2-containing PM
      like liposomes consistent with an oligomerization-driven STIM1 activation. In
      contrast, dimerization of STIM2 K-rich domain was sufficient for lipid binding.
      Furthermore, the K-rich domain of STIM2, but not of STIM1, forms an amphipathic
      alpha-helix. These distinct features of the STIM2 K-rich domain cause an
      increased affinity for PI(4,5)P2, consistent with the lower activation threshold
      of STIM2 and a function as regulator of basal Ca2+ levels. Concomitant with
      higher affinity for PM lipids, binding of CaM (calmodulin) inhibited the
      interaction of the STIM2 K-rich domain with liposomes in a Ca2+ and PI(4,5)P2
      concentration-dependent manner. Therefore we suggest that elevated cytosolic Ca2+
      concentration down-regulates STIM2-mediated ER-PM contacts via CaM binding. 

PMID- 24044357
TI  - Fate and transport of antimicrobials and antimicrobial resistance genes in soil
      and runoff following land application of swine manure slurry.
AB  - Due to the use of antimicrobials in livestock production, residual antimicrobials
      and antimicrobial resistance genes (ARGs) could enter the environment following
      the land application of animal wastes and could further contaminate surface and
      groundwater. The objective of this study was to determine the effect of various
      manure land application methods on the fate and transport of antimicrobials and
      ARGs in soil and runoff following land application of swine manure slurry. Swine
      manure slurries were obtained from facilities housing pigs that were fed
      chlortetracyline, tylosin or bacitracin and were land applied via broadcast,
      incorporation, and injection methods. Three rainfall simulation tests were then
      performed on amended and control plots. Results show that land application
      methods had no statistically significant effect on the aqueous concentrations of
      antimicrobials in runoff. However, among the three application methods tested
      broadcast resulted in the highest total mass loading of antimicrobials in runoff
      from the three rainfall simulation tests. The aqueous concentrations of
      chlortetracyline and tylosin in runoff decreased in consecutive rainfall events,
      although the trend was only statistically significant for tylosin. For ARGs,
      broadcast resulted in significantly higher erm genes in runoff than did
      incorporation and injection methods. In soil, the effects of land application
      methods on the fate of antimicrobials in top soil were compound specific. No
      clear trend was observed in the ARG levels in soil, likely because different host
      cells may respond differently to the soil environments created by various land
      application methods. 

PMID- 24044358
TI  - Patchy particle self-assembly via metal coordination.
AB  - Colloids with high-symmetry patches are functionalized with metal-coordination
      based recognition units and assembled into larger chain architectures,
      demonstrating for the first time the use of metal coordination as a specific
      force in colloidal self-assembly. The cross-linked poly(styrene)-based patchy
      particles are fabricated by encapsulation of colloidal clusters following a two
      stage swelling and polymerization methodology. The particle patches, containing
      carboxylic acid groups, are site-specifically functionalized either with a
      triblock copolymer (TBC), bearing primary alcohols, alkyl chains, and palladated
      pincer receptors, synthesized by ring-opening metathesis polymerization, or with
      a small molecule bearing a pyridine headgroup. Functionalizing with a TBC
      provides design flexibility for independently setting the range of the
      interaction and the recognition motif. 

PMID- 24044359
TI  - Radioelectric asymmetric conveyed fields and human adipose-derived stem cells
      obtained with a nonenzymatic method and device: a novel approach to multipotency.
AB  - Human adipose-derived stem cells (hASCs) have been recently proposed as a
      suitable tool for regenerative therapies for their simple isolation procedure and
      high proliferative capability in culture. Although hASCs can be committed into
      different lineages in vitro, the differentiation is a low-yield and often
      incomplete process. We have recently developed a novel nonenzymatic method and
      device, named Lipogems, to obtain a fat tissue derivative highly enriched in
      pericytes/mesenchymal stem cells by mild mechanical forces from human
      lipoaspirates. When compared to enzymatically dissociated cells, Lipogems-derived
      hASCs exhibited enhanced transcription of vasculogenic genes in response to
      provasculogenic molecules, suggesting that these cells may be amenable for
      further optimization of their multipotency. Here we exposed Lipogems-derived
      hASCs to a radioelectric asymmetric conveyer (REAC), an innovative device
      asymmetrically conveying radioelectric fields, affording both enhanced
      differentiating profiles in mouse embryonic stem cells and efficient direct
      multilineage reprogramming in human skin fibroblasts. We show that specific REAC
      exposure remarkably enhanced the transcription of prodynorphin, GATA-4, Nkx-2.5,
      VEGF, HGF, vWF, neurogenin-1, and myoD, indicating the commitment toward cardiac,
      vascular, neuronal, and skeletal muscle lineages, as inferred by the
      overexpression of a program of targeted marker proteins. REAC exposure also
      finely tuned the expression of stemness-related genes, including NANOG, SOX-2,
      and OCT-4. Noteworthy, the REAC-induced responses were fashioned at a
      significantly higher extent in Lipogems-derived than in enzymatically dissociated
      hASCs. Therefore, REAC-mediated interplay between radioelectric asymmetrically
      conveyed fields and Lipogems-derived hASCs appears to involve the generation of
      an ideal "milieu" to optimize multipotency expression from human adult stem cells
      in view of potential improvement of future cell therapy efforts. 

PMID- 24044360
TI  - Standard recommendations for the application of Chinese clinical cell therapy for
      neurorestoration (2012).
AB  - Cell therapy has been shown to be a promising alternative therapy for
      neurorestoration, and more than 30 different types of cells have been shown to
      possess some capability to restore lost or damaged neurological functions.
      Chinese physicians have successfully applied cell therapy to many neurological
      diseases and damages in the clinic and contributed to establish a discipline of
      neurorestoratology. To standardize the clinical procedures of cell therapy as one
      of the strategies for treating neurological disorders, the Chinese Branch of the
      International Association of Neurorestoratology (IANR) and the Preparatory
      Committee of Chinese Association of Neurorestoratology recently completed the
      Standard Recommendations (2012) for the Application of Chinese Clinical Cell
      Therapy for Neurorestoration. We hope these recommendations will guide clinical
      practice in applying cell therapy for neurorestoration, which will therein offer
      a reference for both Chinese and other countries' governments to make relevant
      official regulations. This manuscript is published as part of the International
      Association of Neurorestoratology (IANR) supplement issue of Cell
      Transplantation. 

PMID- 24044361
TI  - Cotransplantation of olfactory ensheathing cells and Schwann cells combined with
      treadmill training promotes functional recovery in rats with contused spinal
      cords.
AB  - The present study investigated the ability of cotransplantation of Schwann cells
      (SCs) and olfactory ensheathing cells (OECs) combined with treadmill training in
      facilitating neuronal plasticity and promoting hindlimb function recovery of
      subacute moderate thoracic (T10) spinal cord contusion in rats. Two weeks
      postinjury, SCs were injected directly into the lesion, while OECs were injected
      into the adjacent tissues. The treadmill training with the rats began postinjury
      on day 7, with each session lasting 20 +/- 10 min per day, 5 days per week, for
      10 weeks. At the 11th week postinjury, OECs were found migrating longitudinally
      and laterally from the injection site to the injury site through the gray and
      white matter, while some traveled along the central canal or pia. The SCs
      remained densely packed and concentrated at the transplant site. The transplanted
      SCs supported ingrowth of numerous, densely populated neurofilament-positive
      (NF(+)), MBP(+) axons. The OECs promoted elongation of moderate NF(+), GAP-43(+)
      axons and a few MBP(+) axons in parallel with OEC processes. The GFAP
      immunoreactivity in the spared tissue surrounding the graft of SCs and OECs at
      the lesion site was less intense than that in the DMEM group. Treadmill training
      had no effect on GFAP immunoreactivity. Treadmill training increased the number
      of TH-immunoreactive neurons in the gray matter of L2 spinal cord. Moreover,
      cotransplantation of OECs and SCs significantly increased the BBB score during 5
      8 weeks postinjury alongside treadmill training between 5 and 11 weeks.
      Cotransplantation of OECs and SCs combined with treadmill training resulted in
      the highest BBB score at 4 and 11 weeks. The study details the differential
      mechanisms of neuronal plasticity: (1) axon growth and remyelination induced by
      cotransplantation of OECs and SCs and (2) neuron plasticity below the lesion
      enhanced by treadmill training. The synergistic effects of the combined strategy
      enhance functional recovery. This manuscript is published as part of the
      International Association of Neurorestoratology (IANR) supplement issue of Cell
      Transplantation.

PMID- 24044363
TI  - Experimental and computational studies on newly synthesized resveratrol
      derivative: a new method for cancer chemoprevention and therapeutics?
AB  - Nature has been a provenance of medicinal agents for thousands of years.
      Resveratrol (RESL) is a naturally occurring polyphenolic compound in food stuffs
      such as peanuts, seeds, berries, grapes, and beverages (red wine). RESL has
      received significant attention due to a plethora of in vitro and in vivo reports
      on its cancer chemopreventive and therapeutic properties. In the present study,
      diacetate RESL derivative (RESL43) was synthesized. The RESL43 displayed potent
      cytotoxicity and triggered apoptosis in U937 cells as evidenced by poly (ADP
      ribose) polymerase (PARP) cleavage, DNA fragmentation, morphological changes, and
      activation of FasR and FasL genes. The electrophoretic mobility shift assay
      revealed the suppression NFkB activity in U937 cells after treatment with RESL43
      in corroboration with the deactivation of NFkB dependent genes such as IL-8,
      TNFR, and TNFalpha. Furthermore, molecular docking and dynamics studies have
      shown that RESL and RESL43 might exert their inhibitory activity on NFkB by
      altering the intramolecular binding abilities between DNA and NFkB. Taken
      together, RESL43 can have greater putative activity than parental RESL in a
      context of cancer chemoprevention and therapeutics. We suggest that the diacetate
      resveratrol derivative RESL43 warrants further evaluation in preclinical and
      clinical bridging studies in the near future.

PMID- 24044362
TI  - Agrigenomics for microalgal biofuel production: an overview of various
      bioinformatics resources and recent studies to link OMICS to bioenergy and
      bioeconomy.
AB  - Microalgal biofuels offer great promise in contributing to the growing global
      demand for alternative sources of renewable energy. However, to make algae-based
      fuels cost competitive with petroleum, lipid production capabilities of
      microalgae need to improve substantially. Recent progress in algal genomics, in
      conjunction with other "omic" approaches, has accelerated the ability to identify
      metabolic pathways and genes that are potential targets in the development of
      genetically engineered microalgal strains with optimum lipid content. In this
      review, we summarize the current bioeconomic status of global biofuel feedstocks
      with particular reference to the role of "omics" in optimizing sustainable
      biofuel production. We also provide an overview of the various databases and
      bioinformatics resources available to gain a more complete understanding of lipid
      metabolism across algal species, along with the recent contributions of "omic"
      approaches in the metabolic pathway studies for microalgal biofuel production.

PMID- 24044364
TI  - Postgenomics diagnostics: metabolomics approaches to human blood profiling.
AB  - We live in exciting times with the prospects of postgenomics diagnostics.
      Metabolomics is a novel "omics" data-intensive science that is accelerating the
      development of postgenomics diagnostics, particularly with use of accessible
      peripheral tissue compartments. Metabolomics involves the study of a
      comprehensive set of low molecular weight substances (metabolites) present in
      biological systems. The metabolite profiles represent the molecular phenotype of
      biological systems and reflect the information encoded at the genomic level and
      implemented at the transcriptomic and proteomic levels. Analysis of the human
      blood metabolite profile is a universal and highly promising tool for clinical
      postgenomics applications because it reflects both the endogenous and exogenous
      (environmental) factors influencing an individual organism. This article presents
      a critical synthesis and original analysis of both the technical implementation
      of metabolic profiling of blood and statistical analysis of metabolite profiles
      for effective disease diagnostics and risk assessment in the present postgenomics
      era.

PMID- 24044365
TI  - A comprehensive metabolic modeling of thyroid pathway in relation to thyroid
      pathophysiology and therapeutics.
AB  - The thyroid pathway represents a complex interaction of different glands for
      thyroid hormone synthesis. Thyrotropin releasing hormone is synthesized in the
      hypothalamus and regulates thyrotropin stimulating hormone gene expression in the
      pituitary gland. In order to understand the complexity of the thyroid pathways,
      and using experimental data retrieved from the biomedical literature (e.g., NCBI,
      HuGE Navigator, Protein Data Bank, and KEGG), we constructed a metabolic map of
      the thyroid hormone pathway at a molecular level and analyzed it topologically. A
      total of five hub nodes were predicted in regards to the transcription thyroid
      receptor (TR), cAMP response element-binding protein (CREB), signal transducer
      and activator of transcription 3 (STAT 3), nuclear factor kappa-light-chain
      enhancer of activated B cells (NFkB), and activator protein 1 (AP-1) as being
      potentially important in study of thyroid disorders and as novel putative
      therapeutic drug targets. Notably, the thyroid receptor is a highly connected hub
      node and currently used as a therapeutic target in hypothyroidism. Our analysis
      represents the first comprehensive description of the thyroid pathway, which
      pertains to understanding the function of the protein and gene interaction
      networks. The findings from this study are therefore informative for
      pathophysiology and rational therapeutics of thyroid disorders.

PMID- 24044366
TI  - Antiviral cationic peptides as a strategy for innovation in global health
      therapeutics for dengue virus: high yield production of the biologically active
      recombinant plectasin peptide.
AB  - Dengue virus infects millions of people worldwide, and there is no vaccine or
      anti-dengue therapeutic available. Antimicrobial peptides have been shown to
      possess effective antiviral activity against various viruses. One of the main
      limitations of developing these peptides as potent antiviral drugs is the high
      cost of production. In this study, high yield production of biologically active
      plectasin peptide was inexpensively achieved by producing tandem plectasin
      peptides as inclusion bodies in E. coli. Antiviral activity of the recombinant
      peptide towards dengue serotype-2 NS2B-NS3 protease (DENV2 NS2B-NS3pro) was
      assessed as a target to inhibit dengue virus replication in Vero cells. Single
      units of recombinant plectasin were collected after applying consecutive steps of
      refolding, cleaving by Factor Xa, and nickel column purification to obtain
      recombinant proteins of high purity. The maximal nontoxic dose (MNTD) of the
      recombinant peptide against Vero cells was 20 MUM (100 MUg/mL). The reaction
      velocity of DENV2 NS2B-NS3pro decreased significantly after increasing
      concentrations of recombinant plectasin were applied to the reaction mixture.
      Plectasin peptide noncompetitively inhibited DENV2 NS2B-NS3pro at Ki value of
      5.03 +/- 0.98 MUM. The percentage of viral inhibition was more than 80% at the
      MNTD value of plectasin. In this study, biologically active recombinant plectasin
      which was able to inhibit dengue protease and viral replication in Vero cells was
      successfully produced in E. coli in a time- and cost- effective method. These
      findings are potentially important in the development of potent therapeutics
      against dengue infection.

PMID- 24044367
TI  - A synthetic curcumin derivative hydrazinobenzoylcurcumin induces autophagy in
      A549 lung cancer cells.
AB  - CONTEXT: Curcumin exhibits growth-suppressive activity against a variety of
      cancer cells, but low bioavailability restricts its application in
      chemotherapeutic trials. Nowadays, a growing number of curcumin derivatives or
      analogs are known, hoping to replace curcumin and circumvent this problem.
      Hydrazinobenzoylcurcumin (HBC) has been synthesized and identified as a potent
      inhibitor of cell proliferation in previous reports. OBJECTIVE: This study
      presents a novel mechanism of cell autophagy induced by HBC in the human non
      small lung epithelial carcinoma (A549) cells. MATERIALS AND METHODS: Cells were
      cultured and treated with HBC at different concentrations (10-80 MUM) and at
      different time periods (1-24 h). Microscopic analysis was used to detect the
      morphology changes and autophagolysosomes of A549 cells. An acridine orange
      staining assay was conducted to evaluate the autophagolysosomes and autophagic
      vacuoles was analyzed by monodansylcadaverine (MDC) and GFP-LC3 transfection
      analysis. Western blotting was used to assess the conversion of microtubule
      associated protein light chain 3 (LC3). RESULTS: HBC could induce A549 cells
      autophagolysosomes formation in a dose and time-dependent manner and the
      inhibitory rate of HBC (80 MUM) on the viability of A549 cells reached 76.68 +/-
      5.81% after 24 h of treatment. Autophagic vacuoles increased in a concentration
      dependent manner in HBC-treated cell. Furthermore, conversion of LC3-I to LC3-II,
      accumulation of GFP-tagged LC3 positive intracellular vacuoles and increased
      fusion of autophagosomes with lysosomes suggested the occurrence of autophagy.
      CONCLUSION: Our data indicate that HBC induced A549 cell autophagy, which is a
      novel cell death mechanism induced by curcumin derivatives.

PMID- 24044368
TI  - Household catastrophic payments for tuberculosis care in Nigeria: incidence,
      determinants, and policy implications for universal health coverage.
AB  - BACKGROUND: Studies on costs incurred by patients for tuberculosis (TB) care are
      limited as these costs are reported as averages, and the economic impact of the
      costs is estimated based on average patient/household incomes. Average
      expenditures do not represent the poor because they spend less on treatment
      compared to other economic groups. Thus, the extent to which TB expenditures risk
      sending households into, or further into, poverty and its determinants, is
      unknown. We assessed the incidence and determinants of household catastrophic
      payments for TB care in rural Nigeria. METHODS: Data used were obtained from a
      survey of 452 pulmonary TB patients sampled from three rural health facilities in
      Ebonyi State, Nigeria. Using household direct costs and income data, we analyzed
      the incidence of household catastrophic payments using, as thresholds, the
      traditional >10% of household income and the >=40% of non-food income, as
      recommended by the World Health Organization. We used logistic regression
      analysis to identify the determinants of catastrophic payments. RESULTS: Average
      direct household costs for TB were US$157 or 14% of average annual incomes. The
      incidence catastrophic payment was 44%; with 69% and 15% of the poorest and
      richest household income-quartiles experiencing catastrophic activity,
      respectively. Independent determinants of catastrophic payments were: age >40
      years (adjusted odds ratio [aOR] 3.9; 95% confidence interval [CI], 2.0, 7.8),
      male gender (aOR 3.0; CI 1.8, 5.2), urban residence (aOR 3.8; CI 1.9, 7.7),
      formal education (aOR 4.7; CI 2.5, 8.9), care at a private facility (aOR 2.9;
      1.5, 5.9), poor household (aOR 6.7; CI 3.7, 12), household where the patient is
      the primary earner (aOR 3.8; CI 2.2, 6.6]), and HIV co-infection (aOR 3.1; CI
      1.7, 5.6). CONCLUSIONS: Current cost-lowering strategies are not enough to
      prevent households from incurring catastrophic out-of-pocket payments for TB
      care. Financial and social protection interventions are needed for identified at
      risk groups, and community-level interventions may reduce inefficiencies in the
      care-seeking pathway. These observations should inform post-2015 TB strategies
      and influence policy-making on health services that are meant to be free of
      charge.

PMID- 24044369
TI  - Control of mode/bond selectivity and product energy disposal by the transition
      state: X + H2O (X = H, F, O(3P), and Cl) reactions.
AB  - The ability to predict mode/bond selectivity and energy disposal is of central
      importance for controlling chemical reactions. We argue that the transition state
      plays a critical role in state-to-state reactivity and propose a simple sudden
      model based on coupling with the reaction coordinate at the transition state. The
      applicability of this so-called sudden vector projection (SVP) model is examined
      for several prototypical atom-triatom, namely, X + H2O (X = H, F, O((3)P), and
      Cl) reactions. It is shown that the SVP model is capable of qualitatively
      predicting experimental and full-dimensional quantum dynamical results, including
      those reported in this work, for these polyatomic reactions. These results, and
      those for other reactions, suggest that the SVP model offers a general paradigm
      for understanding quantum state resolved reactivity in bimolecular reactions. 

PMID- 24044370
TI  - The potential impact on obesity of a 10% tax on sugar-sweetened beverages in
      Ireland, an effect assessment modelling study.
AB  - BACKGROUND: Some governments have recently shown a willingness to introduce taxes
      on unhealthy foods and drinks. In 2011, the Irish Minister for Health proposed a
      10% tax on sugar sweetened beverages (SSBs) as a measure to combat childhood
      obesity. Whilst this proposed tax received considerable support, the Irish
      Department of Finance requested a Health Impact Assessment of this measure. As
      part of this assessment we set out to model the impact on obesity. METHODS: We
      used price elasticity estimates to calculate the effect of a 10% SSB tax on SSB
      consumption. SSBs were assumed to have an own-price elasticity of -0.9 and we
      assumed a tax pass-on rate to consumers of 90%. Baseline SSB consumption and
      obesity prevalence, by age, sex and income-group, for Ireland were taken from the
      2007 Survey on Lifestyle and Attitude to Nutrition. A comparative risk assessment
      model was used to estimate the effect on obesity arising from the predicted
      change in calorie consumption, both for the whole population and for sub-groups
      (age, sex, income). Sensitivity analyses were conducted on price-elasticity
      estimates and tax pass-on rates. RESULTS: We estimate that a 10% tax on SSBs will
      result in a mean reduction in energy intake of 2.1 kcal/person/day. After
      adjustment for self-reported data, the 10% tax is predicted to reduce the
      percentage of the obese adult population (body mass index [BMI] >= 30 kg/m(2)) by
      1.3%, equating to 9,900 adults (95% credible intervals: 7,750 to 12,940), and the
      overweight or obese population (BMI >= 25 kg/m(2)) by 0.7%, or 14,380 adults
      (9,790 to 17,820). Reductions in obesity are similar for men (1.2%) and women
      (1.3%), and similar for each income group (between 1.1% and 1.4% across income
      groups). Reductions in obesity are greater in young adults than older adults
      (e.g. 2.9% in adults aged 18-24 years vs 0.6% in adults aged 65 years and over).
      CONCLUSIONS: This study suggests that a tax on SSBs in Ireland would have a small
      but meaningful effect on obesity. While such a tax would be perceived as
      affecting the whole population, from a health prospective the tax will
      predominantly affect younger adults who are the main consumers of SSBs.

PMID- 24044372
TI  - High prevalence of Nova hantavirus infection in the European mole (Talpa
      europaea) in France.
AB  - SUMMARY: Recent discovery of genetically distinct hantaviruses in shrews and
      moles (order Soricomorpha, family Soricidae and Talpidae) has challenged the
      conventional view that rodents serve as the principal reservoir hosts. Nova virus
      (NVAV), previously identified in archival liver tissue of a single European mole
      (Talpa europaea) from Hungary, represents one of the most highly divergent
      hantaviruses identified to date. To ascertain the spatial distribution and
      genetic diversity of NVAV, we employed RT-PCR to analyse lungs from 94 moles,
      captured in two locations in France, during October 2012 to March 2013. NVAV was
      detected in more than 60% of moles at each location, suggesting efficient
      enzootic virus transmission and confirming that this mole species serves as the
      reservoir host. Although the pathogenic potential of NVAV is unknown, the
      widespread geographical distribution of the European mole might pose a hantavirus
      exposure risk for humans.

PMID- 24044371
TI  - Malarial parasite diversity in chimpanzees: the value of comparative approaches
      to ascertain the evolution of Plasmodium falciparum antigens.
AB  - BACKGROUND: Plasmodium falciparum shares its most recent common ancestor with
      parasites found in African apes; these species constitute the so-called Laverania
      clade. In this investigation, the evolutionary history of Plasmodium lineages
      found in chimpanzees (Pan troglodytes) was explored. METHODS: Here, the
      remainders of 74 blood samples collected as part of the chimpanzees' routine
      health examinations were studied. For all positive samples with parasite lineages
      belonging to the Laverania clade, the complete mitochondrial genome (mtDNA), the
      gene encoding dihydrofolate reductase-thymidylate synthase (dhfr-ts), the
      chloroquine resistance transporter (Pfcrt), the circumsporozoite protein (csp),
      merozoite surface protein 2 (msp2), and the DBL-1 domain from var2CSA were
      amplified, cloned, and sequenced. Other Plasmodium species were included in the
      mtDNA, dhfr-ts, and csp analyses. Phylogenetic and evolutionary genetic analyses
      were performed, including molecular clock analyses on the mtDNA.
      RESULTS/CONCLUSIONS: Nine chimpanzees were malaria positive (12.2%); four of
      those infections were identified as P. falciparum, two as a Plasmodium reichenowi
      like parasite or Plasmodium sp., one as Plasmodium gaboni, and two as Plasmodium
      malariae. All P. falciparum isolates were resistant to chloroquine indicating
      that the chimpanzees acquired such infections from humans in recent times. Such
      findings, however, are not sufficient for implicating chimpanzees as an animal
      reservoir for P. falciparum.Timing estimates support that the Laverania clade has
      co-existed with hominids for a long-period of time. The proposed species P.
      gaboni, Plasmodium billbrayi, and Plasmodium billcollinsi are monophyletic groups
      supporting that they are indeed different species.An expanded CSP phylogeny is
      presented, including all the Laverania species and other malarial parasites.
      Contrasting with other Plasmodium, the Laverania csp exhibits great conservation
      at the central tandem repeat region. Msp2 and var2CSA, however, show extended
      recent polymorphism in P. falciparum that likely originated after the P.
      reichenowi-P. falciparum split. The accumulation of such diversity may indicate
      adaptation to the human host. These examples support the notion that comparative
      approaches among P. falciparum and its related species will be of great value in
      understanding the evolution of proteins that are important in parasite invasion
      of the human red blood cell, as well as those involved in malaria pathogenesis.

PMID- 24044373
TI  - Improving the health and well-being of community-dwelling caregivers of dementia
      sufferers: study protocol of a randomized controlled trial of structured
      meditation training.
AB  - BACKGROUND: Caring for a person with dementia can be an unrelenting and
      burdensome task, one that is often detrimental to the caregiver's health, well
      being, and functionality. The enduring stress and frustration of the caregiver
      role can also contribute to poorer outcomes for dementia sufferers. Building on
      growing clinical interest in the capacity for Transcendental Meditation((r)) (TM;
      a relaxation technique) to reduce stress and anxiety in healthy workers, this
      study examines whether similar improvements could be experienced by dementia
      caregivers. OBJECTIVE: The study objective was to ascertain whether a TM program
      can improve psychological stress, quality of life, affect, and cognitive
      performance of dementia caregivers. DESIGN: The study was a pilot prospective,
      single-center, randomized wait-list controlled trial with two parallel arms.
      SETTING/SUBJECTS: Community-dwelling carers of persons with diagnosed dementia,
      residing in metropolitan Adelaide, South Australia, were included in this study.
      INTERVENTIONS: Participants will be randomly assigned to a 13-hour TM training
      program or wait-list control over 12 weeks. OUTCOMES: Primary outcomes include
      quality of life and stress. Secondary outcomes include affect, cognitive
      performance, cost-effectiveness, and study feasibility. Outcomes will be assessed
      at baseline, week 12 (postintervention), and week 24 (follow-up). RESULTS:
      Results are expected to be available early in 2014. CONCLUSIONS: This project
      responds to a need for robust evidence of the clinical and economic effectiveness
      of TM for the management of caregiver stress. If Transcendental Meditation is
      shown to be effective, it could indicate a simple, cost-effective, and easily
      implemented strategy to assist many of the growing numbers of caregivers to cope
      with the demanding and often difficult caregiver role.

PMID- 24044374
TI  - Morbidity and doctor characteristics only partly explain the substantial
      healthcare expenditures of frequent attenders: a record linkage study between
      patient data and reimbursements data.
AB  - BACKGROUND: Frequently attending patients to primary care (FA) are likely to cost
      more in primary care than their non-frequently attending counterparts. But how
      much is spent on specialist care of FAs? We describe the healthcare expenditures
      of frequently attending patients during 1, 2 or 3 years and test the hypothesis
      that additional costs can be explained by FAs' combined morbidity and primary
      care physicians' characteristics. METHODS: Record linkage study. Pseudonymised
      clinical data from the medical records of 16 531 patients from 39 general
      practices were linked to healthcare insurer's reimbursements data. Main outcome
      measures were all reimbursed primary and specialist healthcare costs between 2007
      and 2009. Multilevel linear regression analysis was used to quantify the effects
      of the different durations of frequent attendance on three-year total healthcare
      expenditures in primary and specialist care, while adjusting for age, sex,
      morbidities and for primary care physicians characteristics. Primary care
      physicians' characteristics were collected through administrative data and a
      questionnaire. RESULTS: Unadjusted mean 3-year expenditures were 5044 and 15 824
      Euros for non-FAs and three-year-FAs, respectively. After adjustment for all
      other included confounders, costs both in primary and specialist care remained
      substantially higher and increased with longer duration of frequent attendance.
      As compared to non-FAs, adjusted mean expenditures were 1723 and 5293 Euros
      higher for one-year and three-year FAs, respectively. CONCLUSIONS: FAs of primary
      care give rise to substantial costs not only in primary, but also in specialist
      care that cannot be explained by their multimorbidity. Primary care physicians'
      working styles appear not to explain these excess costs. The mechanisms behind
      this excess expenditure remain to be elucidated.

PMID- 24044375
TI  - Inducible nitric oxide synthase expression in gastric adenocarcinoma: impact on
      lymphangiogenesis and lymphatic metastasis.
AB  - BACKGROUND: Lymphatic metastasis is the most important parameter in the spread of
      gastric carcinomas. Nitric oxide (NO) is a signaling molecule that plays an
      important role in inflammation and carcinogenesis. In this study, the possible
      link between inducible nitric oxide synthase (iNOS) expression with
      lymphangiogenesis and the clinicopathological parameters of gastric carcinomas
      was investigated. METHODS: In this study, iNOS expression and D2-40 (lymphatic
      endothelium-specific marker monoclonal antibody) reactivity were examined
      immunohistochemically in 41 gastric adenocarcinoma and 20 non-neoplastic gastric
      tissues. iNOS expression was scored semiquantitatively in the tumor parenchyma
      and stroma. D2-40-positive lymphatic vessels were used in the determination of
      lymphatic invasion and intratumoral and peritumoral lymphatic vascular density.
      RESULTS: iNOS expression was higher in gastric carcinoma tissue compared with non
      neoplastic tissue. Particularly, iNOS expression in tumor cells was found to be
      closely related to lymphangiogenesis and lymphatic metastasis. The density of
      lymphatic invasion as well as intratumoral and peritumoral lymphatic vascular
      density were positively correlated with lymph node metastasis. CONCLUSIONS: Our
      results suggest that iNOS-mediated NO formation plays an important role in
      gastric carcinogenesis, tumor lymphangiogenesis, and the development of lymphatic
      metastases. Inhibition of the NO pathway may be an alternative treatment of
      gastric carcinomas. VIRTUAL SLIDES: The virtual slides for this article can be
      found here: http://www.diagnosticpathology.diagnomx.eu/vs/1713572940104388.

PMID- 24044376
TI  - Reliability of clinically relevant 3D foot bone angles from quantitative computed
      tomography.
AB  - BACKGROUND: Surgical treatment and clinical management of foot pathology requires
      accurate, reliable assessment of foot deformities. Foot and ankle deformities are
      multi-planar and therefore difficult to quantify by standard radiographs. Three
      dimensional (3D) imaging modalities have been used to define bone orientations
      using inertial axes based on bone shape, but these inertial axes can fail to
      mimic established bone angles used in orthopaedics and clinical biomechanics. To
      provide improved clinical relevance of 3D bone angles, we developed techniques to
      define bone axes using landmarks on quantitative computed tomography (QCT) bone
      surface meshes. We aimed to assess measurement precision of landmark-based, 3D
      bone-to-bone orientations of hind foot and lesser tarsal bones for expert raters
      and a template-based automated method. METHODS: Two raters completed two
      repetitions each for twenty feet (10 right, 10 left), placing anatomic landmarks
      on the surfaces of calcaneus, talus, cuboid, and navicular. Landmarks were also
      recorded using the automated, template-based method. For each method, 3D bone
      axes were computed from landmark positions, and Cardan sequences produced
      sagittal, frontal, and transverse plane angles of bone-to-bone orientations.
      Angular reliability was assessed using intraclass correlation coefficients (ICCs)
      and the root mean square standard deviation (RMS-SD) for intra-rater and inter
      rater precision, and rater versus automated agreement. RESULTS: Intra- and inter
      rater ICCs were generally high (>= 0.80), and the ICCs for each rater compared to
      the automated method were similarly high. RMS-SD intra-rater precision ranged
      from 1.4 to 3.6 degrees  and 2.4 to 6.1 degrees , respectively, for the two
      raters, which compares favorably to uni-planar radiographic precision. Greatest
      variability was in Navicular: Talus sagittal plane angle and Cuboid: Calcaneus
      frontal plane angle. Precision of the automated, atlas-based template method
      versus the raters was comparable to each rater's internal precision. CONCLUSIONS:
      Intra- and inter-rater precision suggest that the landmark-based methods have
      adequate test-retest reliability for 3D assessment of foot deformities. Agreement
      of the automated, atlas-based method with the expert raters suggests that the
      automated method is a valid, time-saving technique for foot deformity assessment.
      These methods have the potential to improve diagnosis of foot and ankle
      pathologies by allowing multi-planar quantification of deformities.

PMID- 24044377
TI  - Comparing a few SNP calling algorithms using low-coverage sequencing data.
AB  - BACKGROUND: Many Single Nucleotide Polymorphism (SNP) calling programs have been
      developed to identify Single Nucleotide Variations (SNVs) in next-generation
      sequencing (NGS) data. However, low sequencing coverage presents challenges to
      accurate SNV identification, especially in single-sample data. Moreover, commonly
      used SNP calling programs usually include several metrics in their output files
      for each potential SNP. These metrics are highly correlated in complex patterns,
      making it extremely difficult to select SNPs for further experimental
      validations. RESULTS: To explore solutions to the above challenges, we compare
      the performance of four SNP calling algorithm, SOAPsnp, Atlas-SNP2, SAMtools, and
      GATK, in a low-coverage single-sample sequencing dataset. Without any post-output
      filtering, SOAPsnp calls more SNVs than the other programs since it has fewer
      internal filtering criteria. Atlas-SNP2 has stringent internal filtering
      criteria; thus it reports the least number of SNVs. The numbers of SNVs called by
      GATK and SAMtools fall between SOAPsnp and Atlas-SNP2. Moreover, we explore the
      values of key metrics related to SNVs' quality in each algorithm and use them as
      post-output filtering criteria to filter out low quality SNVs. Under different
      coverage cutoff values, we compare four algorithms and calculate the empirical
      positive calling rate and sensitivity. Our results show that: 1) the overall
      agreement of the four calling algorithms is low, especially in non-dbSNPs; 2) the
      agreement of the four algorithms is similar when using different coverage
      cutoffs, except that the non-dbSNPs agreement level tends to increase slightly
      with increasing coverage; 3) SOAPsnp, SAMtools, and GATK have a higher empirical
      calling rate for dbSNPs compared to non-dbSNPs; and 4) overall, GATK and Atlas
      SNP2 have a relatively higher positive calling rate and sensitivity, but GATK
      calls more SNVs. CONCLUSIONS: Our results show that the agreement between
      different calling algorithms is relatively low. Thus, more caution should be used
      in choosing algorithms, setting filtering parameters, and designing validation
      studies. For reliable SNV calling results, we recommend that users employ more
      than one algorithm and use metrics related to calling quality and coverage as
      filtering criteria.

PMID- 24044378
TI  - Biomimetic total syntheses of borreverine and flinderole alkaloids.
AB  - Dimeric indole alkaloids represent a structurally unique class of natural
      products having interesting biological activities. Recently, we reported the
      first total synthesis of flinderoles B and C, structurally unique and potent
      antimalarial natural products. Central to the design of the approach and by
      virtue of a one-pot, acid-catalyzed dimerization reaction, the route also
      provided total synthesis of the borreverine class of natural products. This full
      account details the progress of efforts that culminated in the protecting-group
      free, six-step total synthesis of all of the flindersia alkaloids:
      dimethylisoborreverine, isoborreverine, flinderoles A-C, and their analogues. A
      biomimetic approach featuring a scalable and catalytic formal [3 + 2]
      cycloaddition and Diels-Alder reaction is outlined in detail. On the basis of the
      experimental observations, a detailed mechanism has been proposed for the
      dimerization of tertiary alcohol 28. 

PMID- 24044379
TI  - Single-access laparoscopic subtotal spleno-pancreatectomy for pancreatic
      adenocarcinoma.
AB  - Laparoscopic distal or subtotal pancreatectomy can be performed safely and
      effectively unless there is a clear reason why not to do so. With the aim of
      reducing postoperative trauma and improving the cosmesis, single-access
      laparoscopic surgery has been introduced into daily practice. We report the first
      case of distal single-access laparoscopic pancreasectomy for an adenocarcinoma.
      The procedure was carried out in 170 minutes without postoperative complications.
      Despite some technical difficulties, we think that a single-access laparoscopic
      approach could be adequate for a pancreatic resection. However, an adequate
      analysis of cost-effectiveness as well as regarding the reproducibility should be
      carried out.

PMID- 24044380
TI  - Impact of surgical approach on blood loss during intracapsular myomectomy.
AB  - BACKGROUND: Myomectomy is one of the most common surgical procedures in
      gynecology and has implications on fertility and subsequent pregnancies. We
      compared the impact of surgical approach on blood loss during laparoscopic and
      abdominal intracapsular myomectomy. MATERIAL AND METHODS: The evaluation
      comprised 124 fertile women with subserous or intramural myomas: 66 patients
      treated by laparoscopy and 58 patients treated by laparotomy. The intracapsular
      myoma enucleation technique was similar for both approaches. All procedures were
      analyzed for the evaluation of intra- and post-surgical blood loss and intra- and
      short-term post-operative surgical outcomes. RESULTS: The operating time for
      laparoscopic intracapsular myomectomy was longer (95 +/- 7.2 min vs. 63 +/- 5.6,
      p < 0.0001), but was associated with reduced intra- (65 +/- ml vs. 105 +/- 5, p <
      0.0001) and post-surgical blood loss (30 +/- 5 vs. 60 +/- 5 ml, p < 0.0001), as
      well as diminished application of pain relief medication (8 patients vs. 17, p <
      0.05), compared to open intracapsular myomectomy. CONCLUSIONS: The surgical
      approach did not substantially affect the technique of intracapsular myomectomy;
      however, laparoscopy significantly reduced intra- and postoperative blood loss
      and resulted in better short-term outcomes than after open surgery. Our results
      underscore the advantages of trying to reduce the rate of laparotomic myomectomy,
      one of the leading surgical interventions associated with infertility and
      sterility.

PMID- 24044381
TI  - Fabrication and photoresponse of ZnO nanowires/CuO coaxial heterojunction.
AB  - The fabrication and properties of n-ZnO nanowires/p-CuO coaxial heterojunction
      (CH) with a photoresist (PR) blocking layer are reported. In our study, c-plane
      wurtzite ZnO nanowires were grown by aqueous chemical method, and monoclinic CuO
      (111) was then coated on the ZnO nanowires by electrochemical deposition to form
      CH. To improve the device performance, a PR layer was inserted between the ZnO
      buffer layer and the CuO film to serve as a blocking layer to block the leakage
      current. Structural investigations of the CH indicate that the sample has good
      crystalline quality. It was found that our refined structure possesses a better
      rectifying ratio and smaller reverse leakage current. As there is a large on/off
      ratio between light on and off and the major light response is centered at around
      424 nm, the experimental results suggest that the PR-inserted ZnO/CuO CH can be
      used as a good narrow-band blue light detector. 

PMID- 24044382
TI  - Development of a cell sheet transportation technique for regenerative medicine.
AB  - PURPOSE: A transportation technique for cell sheets is necessary to standardize
      regenerative medicine. The aim of this article is to develop and evaluate a new
      transportation technique for cell sheets. MATERIAL AND METHODS: We developed a
      transportation container with three basic functions: the maintenance of interior
      temperature, air pressure, and sterility. The interior temperature and air
      pressure were monitored by a recorder. Human oral mucosal epithelial cells
      obtained from two healthy volunteers were cultured on temperature-responsive
      culture dishes. The epithelial cell sheets were transported via an airplane
      between the Osaka University and Tohoku University using the developed cell
      transportation container. Histological and immunohistochemical analyses and flow
      cytometric analyses for cell viability and cell purity were performed for the
      cell sheets before and 12 h after transportation to assess the influence of
      transportation on the cell sheets. Sterility tests and screening for endotoxin
      and mycoplasma in the cell sheets were performed before and after transportation.
      RESULTS: During transportation via an airplane, the temperature inside the
      container was maintained above 32 degrees C, and the changes in air pressure
      remained within 10 hPa. The cell sheets were well stratified and successfully
      harvested before and after transportation. The expression patterns of keratin
      3/76, p63, and MUC16 were equivalent before and after transportation. However,
      the expression of ZO-1 in the cell sheet after transportation was slightly weaker
      than that before transportation. The cell viability was 72.0% before
      transportation and 77.3% after transportation. The epithelial purity was 94.6%
      before transportation and 87.9% after transportation. Sterility tests and
      screening for endotoxin and mycoplasma were negative for all cell sheets.
      CONCLUSION: The newly developed transportation technique for air travel is
      essential technology for regenerative medicine and promotes the standardization
      and spread of regenerative therapies.

PMID- 24044383
TI  - Engineered antifouling microtopographies: an energetic model that predicts cell
      attachment.
AB  - We have developed a model for the prediction of cell attachment to engineered
      microtopographies based on two previous models: the attachment point theory and
      the engineered roughness index (ERI) model. The new surface energetic attachment
      (SEA) model is based on both the properties of the cell-material interface and
      the size and configuration of the topography relative to the organism. We have
      used Monte Carlo simulation to examine the SEA model's ability to predict
      relative attachment of the green alga Ulva linza to different locations within a
      unit cell. We have also compared the predicted relative attachment for Ulva
      linza, the diatom Navicula incerta, the marine bacterium Cobetia marina, and the
      barnacle cyprid Balanus amphitrite to a wide variety of microtopographies. We
      demonstrate good correlation between the experimental results and the model
      results for all tested experimental data and thus show the SEA model may be used
      as a powerful indicator of the efficacy for antifouling topographies. 

PMID- 24044384
TI  - GIFTS: Graduate Interviews using Faculty, Technology, and Students.
AB  - This article describes an innovative teaching strategy-GIFTS (Graduate Interviews
      using Faculty, Technology, and Students)-that can be used to prepare doctoral
      nursing students for a faculty position interview after graduation. This type of
      educational strategy is needed in the face of the current nurse faculty shortage.
      In addition, it can serve to better prepare novice nurse educators who struggle
      with the transition from clinical practice to academia.

PMID- 24044385
TI  - Web-based unfolding cases: a strategy to enhance and evaluate clinical reasoning
      skills.
AB  - Clinical reasoning involves the use of both analytical and nonanalytical
      intuitive cognitive processes. Fostering student development of clinical
      reasoning skills and evaluating student performance in this cognitive arena can
      challenge educators. The use of Web-based unfolding cases is proposed as a
      strategy to address these challenges. Unfolding cases mimic real-life clinical
      situations by presenting only partial clinical information in sequential
      segments. Students receive immediate feedback after submitting a response to a
      given segment. The student's comparison of the desired and submitted responses
      provides information to enhance the development of clinical reasoning skills.
      Each student's set of case responses are saved for the instructor in an
      individual-student electronic file, providing a record of the student's knowledge
      and thinking processes for faculty evaluation. For the example case given, the
      approaches used to evaluate individual components of clinical reasoning are
      provided. Possible future uses of Web-based unfolding cases are described.

PMID- 24044386
TI  - Flipping the classroom to improve student performance and satisfaction.
AB  - This study aimed to determine the effects of a flipped classroom (i.e., reversal
      of time allotment for lecture and homework) and innovative learning activities on
      academic success and the satisfaction of nursing students. A quasi-experimental
      design was used to compare three approaches to learning: traditional lecture only
      (LO), lecture and lecture capture back-up (LLC), and the flipped classroom
      approach of lecture capture with innovative classroom activities (LCI).
      Examination scores were higher for the flipped classroom LCI group (M = 81.89, SD
      = 5.02) than for both the LLC group (M = 80.70, SD = 4.25), p = 0.003, and the LO
      group (M = 79.79, SD = 4.51), p < 0.001. Students were less satisfied with the
      flipped classroom method than with either of the other methods (p < 0.001).
      Blending new teaching technologies with interactive classroom activities can
      result in improved learning but not necessarily improved student satisfaction.

PMID- 24044387
TI  - A randomised comparison of lidocaine 2% gel and proparacaine 0.5% eye drops in
      paediatric squint surgery.
AB  - We conducted a randomised trial comparing lidocaine 2% gel with proparacaine 0.5%
      eye drops in children having elective squint surgery. One hundred and forty
      children aged between 3 and 14 years were recruited. The requirement for intra
      operative fentanyl and postoperative ibuprofen was significantly less in the
      lidocaine group compared with the proparacaine group (1 (1.7%) vs 12 (18.5%),
      p=0.002 and 16 (27.6%) 38 (58.5%), p=0.001, respectively). The incidence of
      postoperative nausea and vomiting was significantly less in the lidocaine group
      compared with the proparacaine group (6 (10.3%) vs 16 (24.6%), p=0.04). There
      were no differences between the groups in terms of incidence and severity of the
      oculocardiac reflex. We conclude that, compared with proparacaine 0.5% eye drops,
      a single application of lidocaine 2% gel improves peri-operative analgesia and
      reduces the incidence of postoperative nausea and vomiting in elective paediatric
      squint surgery.

PMID- 24044388
TI  - Reaction time-monitored patient-maintained propofol sedation: a pilot study in
      oral surgery patients.
AB  - Previous volunteer studies of an effect-site controlled patient-maintained
      sedation system using propofol have demonstrated a risk of oversedation. We have
      incorporated a reaction time monitor into the handset to add an individualised
      patient-feedback mechanism. This pilot study assessed if the reaction time
      feedback modification would prove safe and effective in 20 healthy patients
      receiving sedation while undergoing oral surgery. All patients successfully
      sedated themselves without reaching any unsafe endpoints. All 20 maintained
      verbal contact throughout. The mean (SD) lowest peripheral blood oxygen
      saturation was 98.0 (2.1)% breathing room air. No patient required supplementary
      oxygen. The mean (SD) maximum effect-site propofol concentration reached was 1.6
      (0.5) MUg.ml(-1). The present system was found to be safe and effective, allowing
      oral surgery treatment under conscious sedation, but preventing oversedation. 

PMID- 24044389
TI  - Awareness during anaesthesia.

PMID- 24044390
TI  - The safety of an interscalene catheter-over-needle technique.

PMID- 24044391
TI  - Short-term heart rate variability in healthy adults.

PMID- 24044392
TI  - Frova introducer and double-lumen tubes.

PMID- 24044393
TI  - One dose fits all? local anaesthetic dosing, clinical trials and safety.

PMID- 24044394
TI  - Obstetric early warning scores: much more work required.

PMID- 24044395
TI  - The use of prone CT in the perioperative management of airway obstruction caused
      by multinodular goitre.

PMID- 24044396
TI  - Remifentanil PCA in labour.

PMID- 24044397
TI  - Physical incompatibility between prochlorperazine, diclofenac and Injekt(r)
      syringe.

PMID- 24044398
TI  - The Judas needle.

PMID- 24044399
TI  - Manufacturers' obligations to colour-code prefilled syringes correctly.

PMID- 24044400
TI  - The safety of paravertebral nerve block.

PMID- 24044401
TI  - Clinical evaluation of the Ambu(r) aScopeTM.

PMID- 24044402
TI  - Subjective and objective experience of pain.

PMID- 24044407
TI  - Accelerated stability and bioassay of a new oral alpha-ketoglutarate formulation
      for treating cyanide poisoning.
AB  - CONTEXT: Due to several limitations of existing cyanide antidotes, alpha
      ketoglutarate (alpha-KG) has been proposed as a promising treatment for cyanide.
      OBJECTIVE: This study reports the accelerated stability and bioassay of a new
      oral alpha-KG formulation. MATERIALS AND METHODS: Amber-colored PVDF bottles
      containing 100 ml of 10% alpha-KG in 70% sorbitol, preservative (sodium methyl
      paraben and sodium propyl paraben), sweetener (sodium saccharine), flavor
      (American ice-cream soda and peppermint) and color (tartrazine), at pH 7.0-8.0
      were stored in stability chamber (40 +/- 2  degrees C and 75 +/- 5% humidity) for
      6 months in a GMP compliant facility. Various physical (pH, color, evaporation,
      extractable volume and clarity), chemical (identification and quantification of
      active ingredient) and microbiological (total aerobic count) analyses, together
      with protection studies were carried periodically in mice. Acute toxicity of the
      formulation and bioavailability of alpha-KG were assessed in rats at the
      beginning of the experiment. RESULTS: No physical changes and microbiological
      growth were observed in the formulation. After 6 months, alpha-KG content in the
      formulation diminished by ~24% but its protective efficacy against cyanide
      remained at 5.9-fold. Protection was further characterized spectrophotometrically
      by disappearance of alpha-KG spectrum in the presence of cyanide, confirming
      cyanohydrin formation. Oral LD50 of alpha-KG formulation in rats was >7.0 g/kg
      body weight, and did not produce any acute toxicity of clinical significance.
      Also, an appreciable amount of alpha-KG was measured in blood. CONCLUSION: As per
      the guidelines of International Conference on Harmonization, the new alpha-KG
      formulation exhibited satisfactory stability, bioefficacy and safety as cyanide
      antidote.

PMID- 24044408
TI  - Sleep wake cycling and neurodevelopmental outcome in very low birth weight
      infants.
AB  - BACKGROUND: Although the maturation of sleep wake cycling (SWC) in premature
      infants has been described, its value in predicting neurodevelopmental outcome
      (NDO) is yet to be known. OBJECTIVE: To examine the relationship between NDO and
      SWC evaluated by amplitude integrated electroencephalogram (aEEG) in very low
      birth weight (VLBW) infants. STUDY DESIGN: VLBW infants (<1500 grams and <=34
      weeks gestational age) were enrolled in a prospective study. Two channel 12-hour
      aEEG recordings were completed at 34 weeks postmenstrual age (PMA) and SWC scores
      were assigned. NDO was measured by the Bayley's Mental Developmental Index (MDI)
      and Psychomotor Developmental Index (PDI) at 9 and 18 months corrected age (CA).
      RESULTS: Eighty-four of the 103 enrolled infants had an aEEG completed at 34
      weeks PMA. At 9 months CA, in linear regression models, MDI was significantly
      associated with severe intraventricular hemorrhage (IVH) and SWC score, while PDI
      was associated with GA and SWC score. At 18 months CA, these associations lost
      significance. CONCLUSIONS: At 34 weeks PMA, all VLBW premature infants
      demonstrate some degree of SWC on aEEG. Maturation of SWC at 34 weeks PMA is not
      associated with gestational age, however may relate to early NDO. Further studies
      are needed to evaluate this relationship.

PMID- 24044410
TI  - A 10-year single-center experience with surgical management of adrenal
      myelolipoma.
AB  - OBJECTIVE: The purpose is to report our 10-year experience with surgical
      management of large or symptomatic adrenal myelolipoma. PATIENTS AND METHODS:
      Patients receiving surgical treatment for adrenal myelolipoma between December
      2001 and September 2011 in our institution were retrospectively reviewed.
      Patients were divided into two groups: open surgery and laparoscopic surgery.
      Patient demographic data, lesion size evaluated by computed tomography scan or
      magnetic resonance imaging, operation time, blood loss, time of returning to
      diets, perioperative complications, and length of hospital stay were collected
      and analyzed. RESULTS: Forty patients (14 received open surgery and 26 received
      laparoscopic surgery) were enrolled in our study. Both procedures were successful
      and no patient in the retroperitoneal laparoscopic group required conversion to
      open surgery. The mean age of the patients was 52.7 years. The median size of the
      tumor was 5.0 cm. Forty-three percent of patients suffered from lumbago. There
      was no statistical difference in perioperative complications between the two
      groups (p>0.05). Retroperitoneal laparoscopic adrenalectomy patients had a
      shorter operation time (90.66+/-37.97 min vs 141.82+/-62.78 min, p=0.017), less
      blood loss (150, 100-200 mL vs 450, 300-525 mL, p=0.000), earlier time of
      returning to diets (2, 2-3 days vs 3, 2-4.5 days, p=0.036), and a shorter
      hospital stay (6, 5-7 days vs 10, 8-11.25 days, p=0.000) when compared with open
      surgery patients. CONCLUSION: Both open and laparoscopic surgeries are efficient
      and safe treatments for large or symptomatic adrenal myelolipoma, and
      retroperitoneal laparoscopic surgery has the advantages of minimal invasion and
      rapid postoperative recovery.

PMID- 24044409
TI  - The chinese american eye study: design and methods.
AB  - PURPOSE: To summarize the study design, operational strategies and procedures of
      the Chinese American Eye Study (CHES), a population-based assessment of the
      prevalence of visual impairment, ocular disease, and visual functioning in
      Chinese Americans. METHODS: This population-based, cross-sectional study included
      4570 Chinese participants aged 50 years and older, residing in the city of
      Monterey Park, California. Each eligible participant completed a detailed
      interview and eye examination. The interview included an assessment of
      demographic, behavioral and ocular risk factors and health-related and vision
      related quality of life. The eye examination included measurements of visual
      acuity, intraocular pressure, visual fields, fundus and optic disc photography, a
      detailed anterior and posterior segment examination, and measurements of blood
      pressure, glycosylated hemoglobin levels, and blood glucose levels. RESULTS: The
      objectives of the CHES are to obtain prevalence estimates of visual impairment,
      refractive error, diabetic retinopathy, open-angle and angle-closure glaucoma,
      lens opacities, and age-related macular degeneration in Chinese Americans. In
      addition, outcomes include effect estimates for risk factors associated with eye
      diseases. Lastly, CHES will investigate the genetic determinants of myopia and
      glaucoma. CONCLUSION: The CHES will provide information about the prevalence and
      risk factors of ocular diseases in one of the fastest growing minority groups in
      the United States.

PMID- 24044411
TI  - Trends of human brucellosis in Italy, 1998-2010.
AB  - SUMMARY: We describe the epidemiological trends and spatial distribution of human
      brucellosis in Italy over 13 years (1998-2010). In the study period 8483 cases
      were notified in Italy, with a relevant decrease (-89%) from 1998 to 2010. Most
      cases were notified in southern Italy (Campania, Apulia, Calabria, Sicily). In
      these regions we observed relevant differences in the risk of brucellosis at
      province level. Cases were distributed with a seasonal pattern, male patients
      represented 60% of the cases and no significant differences were observed between
      age groups. We modelled the underreporting rate that ranged between 2 and 21
      (average 12.5). According to our estimates the true number of cases would have
      ranged from 41 821 to 155 324 providing a far more severe picture of human
      brucellosis in Italy than the one provided by the surveillance system.

PMID- 24044412
TI  - Diels-Alder reactivities of strained and unstrained cycloalkenes with normal and
      inverse-electron-demand dienes: activation barriers and distortion/interaction
      analysis.
AB  - The Diels-Alder reactions of the cycloalkenes, cyclohexene through cyclopropene,
      with a series of dienes--1,3-dimethoxybutadiene, cyclopentadiene, 3,6
      dimethyltetrazine, and 3,6-bis(trifluoromethyl)tetrazine--were studied with
      quantum mechanical calculations and compared with experimental values when
      available. The reactivities of cycloalkenes as dienophiles were found by a
      distortion/interaction analysis to be distortion controlled. The energies
      required for cycloalkenes to be distorted into the Diels-Alder transition states
      increase as the ring size of cycloalkenes increases from cyclopropene to
      cyclohexene, resulting in an increase in activation barriers. The reactivities of
      the dienes are controlled by both distortion and interaction energies. In normal
      Diels-Alder reactions with cycloalkenes, the electron-rich 1,3-dimethoxybutadiene
      exhibits stronger interaction energies than cyclopentadiene, but the high
      distortion energies required for 1,3-dimethoxybutadiene to achieve transition
      state geometries overtake the favorable interaction, resulting in higher
      activation barriers. In inverse-electron-demand Diels-Alder reactions of 3,6
      dimethyltetrazine and 3,6-bis(trifluoromethyl)tetrazine, the reactivities are
      mainly controlled by interaction energies.

PMID- 24044413
TI  - Analysis of the interaction of tarantula toxin Jingzhaotoxin-III (beta-TRTX
      Cj1alpha) with the voltage sensor of Kv2.1 uncovers the molecular basis for cross
      activities on Kv2.1 and Nav1.5 channels.
AB  - Animal venoms contain a fascinating array of divergent peptide toxins that have
      cross-activities on different types of voltage-gated ion channels. However, the
      underlying mechanism remains poorly understood. Jingzhaotoxin-III (JZTX-III), a
      36-residue peptide from the tarantula Chilobrachys jingzhao, is specific for
      Nav1.5 and Kv2.1 channels over the majority of other ion channel subtypes. JZTX
      III traps the Nav1.5 DII voltage sensor at closed state by binding to the DIIS3
      S4 linker. In this study, electrophysiological experiments showed that JZTX-III
      had no effect on five voltage-gated potassium channel subtypes (Kv1.4, Kv3.1, and
      Kv4.1-4.3), whereas it significantly inhibited Kv2.1 with an IC50 of 0.71 +/-
      0.01 MUM. Mutagenesis and modeling data suggested that JZTX-III docks at the
      Kv2.1 voltage-sensor paddle. Alanine replacement of Phe274, Lys280, Ser281,
      Leu283, Gln284, and Val288 could decrease JZTX-III affinity by 7-, 9-, 34-, 12-,
      9-, and 7-fold, respectively. Among them, S281 is the most crucial determinant,
      and the substitution with Thr only slightly reduced toxin sensitivity. In
      contrast, a single conversion of Ser281 to Ala, Phe, Ile, Val, or Glu increased
      the IC50 value by >34-fold. Alanine-scanning mutagenesis experiments indicated
      that the functional surface of JZTX-III bound to the Kv2.1 channel is composed of
      four hydrophobic residues (Trp8, Trp28, Trp30, and Val33) and three charged
      residues (Arg13, Lys15, and Glu34). The bioactive surfaces of JZTX-III
      interacting with Kv2.1 and Nav1.5 are only partially overlapping. These results
      strongly supported the hypothesis that animal toxins might use partially
      overlapping bioactive surfaces to target the voltage-sensor paddles of two
      different types of ion channels. Increasing our understanding of the molecular
      mechanisms of toxins interacting with voltage-gated sodium and potassium channels
      may provide new molecular insights into the design of more potent ion channel
      inhibitors. 

PMID- 24044414
TI  - Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent
      for detecting acidic tumor microenvironments.
AB  - Neoplastic lesions can create a hostile tumor microenvironment with low
      extracellular pH. It is commonly believed that these conditions can contribute to
      tumor progression as well as resistance to therapy. We report the development and
      characterization of a pH-responsive magnetic resonance imaging contrast agent for
      imaging the acidic tumor microenvironment. The preparation included the
      conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5
      dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water-soluble glycol
      chitosan (GC) polymer, which contains pH-titrable primary amines, followed by
      gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate-to-polymer
      ratio of approximately1:24 and a molar relaxivity of 9.1 mM(-1) s(-1). GC-NH2
      GdDOTA demonstrated pH-dependent cellular association in vitro compared to the
      control. It also generated a 2.4-fold enhancement in signal in tumor-bearing mice
      2 h postinjection. These findings suggest that glycol chitosan coupled with
      contrast agents can provide important diagnostic information about the tumor
      microenvironment. 

PMID- 24044415
TI  - Flavonolate complexes of M(II) (M = Mn, Fe, Co, Ni, Cu, and Zn). Structural and
      functional models for the ES (enzyme-substrate) complex of quercetin 2,3
      dioxygenase.
AB  - A series of flavonolate complexes [M(II)L(fla)] (M = Mn (1), Fe (2), Co (3), Ni
      (4), Cu (5), and Zn (6), LH: 2-{[bis(pyridin-2-ylmethyl)amino]methyl}benzoic
      acid, fla: flavonolate) have been synthesized as structural and functional models
      for the ES (enzyme-substrate) complexes of the active site of various M(II)
      containing quercetin 2,3-dioxygenase (2,3-QD) and their structures, spectroscopic
      features, and redox properties, as well as the reactivity toward molecular
      oxygen, have been investigated. The metal centers of [Fe(II)L(fla)].H2O (2),
      [Co(II)L(fla)].CH3OH (3), and [Ni(II)L(fla)] (4) exhibit a distorted octahedral
      geometry with two oxygen atoms of fla, one oxygen atom of the benzoate group of
      ligand L, and three nitrogen atoms of ligand L, in which oxygen atom of the
      carbonyl group of fla and one of the pyridine nitrogen atoms occupy the axial
      positions. The complexes [M(II)L(fla)] exhibit relatively high reactivity in the
      oxidative ring-opening of the bound flavonolate at lower temperature, presumably
      due to the existing carboxylate group in the supporting ligand. Thus, our
      complexes act as good functional ES models of various metal(II)-containing 2,3
      QD. In addition, complexes [Fe(II)L(fla)].H2O (2), [Co(II)L(fla)].CH3OH (3), and
      [Ni(II)L(fla)] (4) are the first structurally characterized Fe(II)-, Co(II)-, and
      Ni(II)-flavonolate complexes, as an active site ES model of Fe(II)-, Co(II)-, and
      Ni(II)-containing 2,3-QD, respectively. The model complexes exhibit notably
      different reactivity in the order of Fe (2) > Cu (5) > Co (3) > Ni (4) > Zn (6) >
      Mn (1). The differences in the reactivity among them may be attributed to the
      redox potential of the coordinated flavonolate of the complexes, which are
      remarkably influenced by the Lewis acidity of the metal ion and its coordination
      environment. Our study is the first example of the metal ion effects on the
      enzyme-like dioxygenation reactivity, providing important insights into the metal
      ion effects on the enzymatic reactivity of various metal(II)-containing 2,3-QD. 

PMID- 24044416
TI  - Sphenostylisins A-K: bioactive modified isoflavonoid constituents of the root
      bark of Sphenostylis marginata ssp. erecta.
AB  - Sphenostylisins A-C (1-3), three complex dimeric compounds representing two novel
      carbon skeletons, along with an additional eight new compounds, sphenostylisins D
      K (4-11), were isolated from the active chloroform-soluble extract of the root
      bark of Sphenostylis marginata ssp. erecta using a bioactivity-guided isolation
      approach. The structures were elucidated by means of detailed spectroscopic
      analysis, including NMR and HRESIMS analysis, and tandem MS fragmentation was
      utilized to further support the structures of 1-3. The absolute configuration of
      sphenostylisin C (3) was established by electronic circular dichroism analysis.
      Plausible biogenetic relationships between the modified isoflavonoids 1-11 are
      proposed, and a cyclization reaction of 9 was conducted to support one of the
      biogenetic proposals made. All of these pure isolates were evaluated against a
      panel of in vitro bioassays, and among the results obtained, sphenostylisin A (1)
      was found to be a very potent NF-kappaB inhibitor (IC50 = 6 nM). 

PMID- 24044417
TI  - Swelling and mechanical properties of alginate hydrogels with respect to
      promotion of neural growth.
AB  - Soft alginate hydrogels support robust neurite outgrowth, but their rapid
      disintegration in solutions of high ionic strength restricts them from long-term
      in vivo applications. Aiming to enhance the mechanical stability of soft alginate
      hydrogels, we investigated how changes in pH and ionic strength during gelation
      influence the swelling, stiffness, and disintegration of a three-dimensional (3D)
      alginate matrix and its ability to support neurite outgrowth. Hydrogels were
      generated from dry alginate layers through ionic crosslinks with Ca(2+) (<= 10
      mM) in solutions of low or high ionic strength and at pH 5.5 or 7.4. High- and
      low-viscosity alginates with different molecular compositions demonstrated pH and
      ionic strength-independent increases in hydrogel volume with decreases in Ca(2+)
      concentrations from 10 to 2 mM. Only soft hydrogels that were synthesized in the
      presence of 150 mM of NaCl (Ca-alginate NaCl) displayed long-term volume
      stability in buffered physiological saline, whereas analogous hydrogels generated
      in NaCl-free conditions (Ca-alginate) collapsed. The stiffnesses of Ca-alginate
      NaCl hydrogels elevated from 0.01 to 19 kPa as the Ca(2+)-concentration was
      raised from 2 to 10 mM; however, only Ca-alginate NaCl hydrogels with an elastic
      modulus <= 1.5 kPa that were generated with <= 4 mM of Ca(2+) supported robust
      neurite outgrowth in primary neuronal cultures. In conclusion, soft Ca-alginate
      NaCl hydrogels combine mechanical stability in solutions of high ionic strength
      with the ability to support neural growth and could be useful as 3D implants for
      neural regeneration in vivo.

PMID- 24044418
TI  - DBP formation in hot and cold water across a simulated distribution system:
      effect of incubation time, heating time, pH, chlorine dose, and incubation
      temperature.
AB  - This paper demonstrates that disinfection byproducts (DBP) concentration profiles
      in heated water were quite different from the DBP concentrations in the cold tap
      water. Chloroform concentrations in the heated water remained constant or even
      decreased slightly with increasing distribution system water age. The amount of
      dichloroacetic acid (DCAA) was much higher in the heated water than in the cold
      water; however, the maximum levels in heated water with different distribution
      system water ages did not differ substantially. The levels of trichloroacetic
      acid (TCAA) in the heated water were similar to the TCAA levels in the tap water,
      and a slight reduction was observed after the tap water was heated for 24 h.
      Regardless of water age, significant reductions of nonregulated DBPs were
      observed after the tap water was heated for 24 h. For tap water with lower water
      ages, there were significant increases in dichloroacetonitrile (DCAN),
      chloropicrin (CP), and 1,1-dichloropropane (1,1-DCP) after a short period of
      heating. Heating of the tap water with low pH led to a more significant increase
      of chloroform and a more significant short-term increase of DCAN. High pH
      accelerated the loss of the nonregulated DBPs in the heated water. The results
      indicated that as the chlorine doses increased, levels of chloroform and DCAA in
      the heated water increased significantly. However, for TCAA, the thermally
      induced increase in concentration was only notable for the chlorinated water with
      very high chlorine dose. Finally, heating may lead to higher DBP concentrations
      in chlorinated water with lower distribution system temperatures. 

PMID- 24044419
TI  - Formation of core-shell structured composite microparticles via cyclic gas-solid
      reactions.
AB  - This work reports a novel low-cost and environmental-friendly preparation
      strategy for core-shell structured composite microparticles and discusses its
      formation mechanism. Different from most conventional strategies, which involve
      coating or coating-like processes, this reported strategy uses irreversible solid
      phase ionic diffusion in a gas-solid reaction cycle (e.g., reduction and
      oxidation of Fe) to gradually move the shell material from a core-and-shell
      material mixture microparticle to the surface. Without the need for solvent as do
      many conventional processes, this novel process only involves gas-solid
      reactions, which reduces environmental impact. To substantiate this conceived
      strategy, a micrometer-sized microparticle made up of a mixture of Fe2O3 and
      Al2O3 powders is first reduced by H2 and then oxidized by O2 over 50 cycles at
      900  degrees C. These reactions are known to proceed mainly through the diffusion
      of solid-phase Fe cations. SEM and EDX analyses verify the formation of an Al2O3
      core-Fe2O3 shell structure at the end of the 50 reaction cycles. If the cyclic
      reactions of a microparticle proceed mainly through the diffusion of gaseous
      reactant-derived O anions such as the mixture of Fe2O3 and TiO2 instead of solid
      phase Fe cation diffusion, no formation of the core-shell structure is observed
      in the resulting microparticle. These two opposing results underscore the
      dominating role of solid-phase ionic diffusion in the formation of the core-shell
      structure. A 2-D continuum diffusion model is applied to account for the inter-Fe
      particle bridging and directional product layer growth phenomena during an
      oxidation reaction. The simulation further verifies the conceived core-shell
      formation strategy. 

PMID- 24044421
TI  - Incidence and economical effects of pneumonia in the older population living in
      French nursing homes: design and methods of the INCUR study.
AB  - BACKGROUND: Among the most burdensome clinical conditions occurring in older
      persons, respiratory infections are particularly relevant. In fact, the onset of
      pneumonias is associated with a significant worsening of the individual's global
      health status and significant increase of healthcare costs. The clinical and
      economical negative consequences of pneumonia may be particularly evident among
      the frailest groups of elders, in particular those living in nursing home.
      Nevertheless, specific research on incidence and economical effects of pneumonia
      in nursing homes residents is still scarce. In the present article, we present
      the rationale, the design and the methods of the "Incidence of pNeumonia and
      related ConseqUences in nursing home Resident (INCUR) study, specifically aimed
      at filling some of the gaps currently present in the field. METHODS/DESIGN: INCUR
      is an observational longitudinal study recruiting 800 residents across 13
      randomly selected nursing homes in France. Multidimensional evaluations of
      participants are conducted at the baseline, mid-term (at 6 months), and end of
      the study (at 12 months) visits in order to measure and follow-up their physical
      function, nutrition, cognition, depression, quality of life, and healthcare
      costs. Incident pneumonia as well as the onset/recurrence of other major health
      related events are monitored during the study follow-up. DISCUSSION: The INCUR
      study will provide valuable information about older persons living in nursing
      homes. Results from INCUR study may constitute the basis for the development of
      future preventive campaigns against pneumonia and its consequences.

PMID- 24044422
TI  - Depression during pregnancy: a risk factor for adverse neonatal outcomes? A
      critical review of the literature.
AB  - OBJECTIVE: We reviewed studies of maternal depression and preterm birth (PTB),
      low birthweight (LBW) and small-for-gestational-age (SGA) in the context of
      methodological differences between studies and potential limitations. METHODS: We
      conducted a literature search of PubMed (1996-2011) for English-language studies
      of maternal depression and (1) PTB and gestational age (GA), (2) LBW and
      birthweight (BW) and (3) SGA. Thirty-six studies met eligibility criteria.
      RESULTS: Elevated depression levels, particularly in early- to mid-pregnancy,
      appear to increase risk of PTB and SGA. Findings suggest an increased risk for
      LBW, but were less consistent. Methodological differences and limitations likely
      contributed to conflicting findings. A wide range of depression measures were
      used with the majority of studies utilizing measures not designed, or validated,
      for pregnant women. Studies failed to assess depression at multiple pregnancy
      time points, thus constraining the ability to assess the impact of duration and
      pattern of exposure to depression. Antidepressant use and co-morbid psychosocial
      factors were rarely considered as potential confounders or effect modifiers.
      CONCLUSIONS: Studies suggest that depression during pregnancy may be an important
      risk factor for PTB and SGA, and possibly LBW. Improved study methodology is
      needed to elucidate the consequence of maternal depression on adverse birth
      outcomes.

PMID- 24044423
TI  - Comparison of robot-assisted and open retropubic radical prostatectomy for risk
      of biochemical progression in men with positive surgical margins.
AB  - OBJECTIVE: Robot-assisted radical prostatectomy (RARP) is a minimally invasive
      alternative to open retropubic radical prostatectomy (RP), and is reported to
      offer equivalent oncologic outcomes while reducing perioperative morbidity.
      However, the technique of extirpation can differ based on the usage of thermal
      energy and coagulation during RARP, which may alter the risk of finding a
      positive surgical margin (PSM) as cautery may destroy residual cancer cells. We
      sought to evaluate whether the method of surgery (RP vs RARP) affects the rate of
      biochemical recurrence (BCR) in patients with PSMs. MATERIALS & METHODS: The
      Columbia University Urologic Oncology Database was reviewed to identify patients
      who underwent RP and RARP from 2000 to 2010 and had a PSM on final pathology. BCR
      was defined as a postoperative prostate-specific antigen (PSA) >=0.2 ng/mL. The
      Kaplan-Meier analysis was utilized to calculate BCR rates based on the method of
      surgery. Cox regression analysis was performed to determine if the method of
      surgery was associated with BCR. RESULTS: We identified 3267 patients who
      underwent prostatectomy, of which 910 (28%) had a PSM. Of those with a PSM, 337
      patients had available follow-up data, including 229 who underwent RP (68%) and
      108 who underwent RARP (32%). At a mean follow-up time of 37 months for the RP
      group, 103 (46%) patients demonstrated BCR; at a mean follow-up time of 44 months
      for the RARP group, 62 (57%) patients had a BCR (p=0.140). Two-year BCR-free
      rates for RP vs RARP were 65% and 49%, respectively (log-rank p<0.001). However,
      after controlling for age, PSA, grade, and year of surgery, the surgical method
      was not significantly associated with increased risk of BCR (HR 1.25; p=0.29).
      CONCLUSION: Our results confirm the noninferiority of RARP to RP with regard to
      patients with PSMs. As such, all patients with a PSM at RP are at high risk for
      BCR and should be followed in the same manner regardless of the surgical
      approach.

PMID- 24044425
TI  - Embellishing personal statements - the hardships of objectivity.

PMID- 24044424
TI  - Outdoor malaria transmission in forested villages of Cambodia.
AB  - BACKGROUND: Despite progress in malaria control, malaria remains an important
      public health concern in Cambodia, mostly linked to forested areas. Large-scale
      vector control interventions in Cambodia are based on the free distribution of
      long-lasting insecticidal nets (LLINs), targeting indoor- and late-biting malaria
      vectors only. The present study evaluated the vector density, early biting
      activity and malaria transmission of outdoor-biting malaria vectors in two
      forested regions in Cambodia. METHODS: In 2005 two entomological surveys were
      conducted in 12 villages and their related forest plots in the east and west of
      Cambodia. Mosquitoes were collected outdoors by human landing collections and
      subjected to enzyme-linked immunosorbent assay (ELISA) to detect Plasmodium
      sporozoites after morphological identification. Blood samples were collected in
      the same villages for serological analyses. Collected data were analysed by the
      classification and regression tree (CART) method and linear regression analysis.
      RESULTS: A total of 11,826 anophelines were recorded landing in 787 man-night
      collections. The majority (82.9%) were the known primary and secondary vectors.
      Most of the variability in vector densities and early biting rates was explained
      by geographical factors, mainly at village level. Vector densities were similar
      between forest and village sites. Based on ELISA results, 29% out of 17
      Plasmodium-positive bites occurred before sleeping time, and 65% in the forest
      plots. The entomological inoculation rates of survey 1 were important predictors
      of the respective seroconversion rates in survey 2, whereas the mosquito
      densities were not. DISCUSSION: In Cambodia, outdoor malaria transmission in
      villages and forest plots is important. In this context, deforestation might
      result in lower densities of the primary vectors, but also in higher densities of
      secondary vectors invading deforested areas. Moreover, higher accessibility of
      the forest could result in a higher man-vector contact. Therefore, additional
      vector control measures should be developed to target outdoor- and early-biting
      vectors.

PMID- 24044426
TI  - Properties of silver nanostructure-coated PTFE and its biocompatibility.
AB  - Silver nanolayers were sputtered on polytetrafluoroethylene (PTFE) and
      subsequently transformed into discrete nanoislands by thermal annealing. The
      Ag/PTFE composites prepared under different conditions were characterized by
      several complementary methods (goniometry, UV-visible spectroscopy, X-ray
      photoelectron spectroscopy, and atomic force microscopy), and new data on the
      mechanism of Ag layer growth and Ag atom clustering under annealing were
      obtained. Biocompatibility of selected Ag/PTFE composites was studied in vitro
      using vascular smooth muscle cell (VSMC) cultures. Despite of the well-known
      inhibitory properties of silver nanostructures towards broad spectrum of
      bacterial strains and cells, it was found that very thin silver coating
      stimulates both adhesion and proliferation of VSMCs. 

PMID- 24044427
TI  - Social, reward, and attention brain networks are involved when online bids for
      joint attention are met with congruent versus incongruent responses.
AB  - Joint attention (JA) is a cornerstone of adaptive human social functioning.
      Little functional magnetic resonance imaging (fMRI) research has examined, in
      interactive paradigms, neural activation underlying bids for JA, met with a
      congruent or an incongruent social response. We developed a highly naturalistic
      fMRI paradigm utilizing eye-tracking to create real-time, contingent social
      responses to participant-initiated JA. During congruent responses to JA bids, we
      observed increased activation in the right amygdala, the right fusiform gyrus,
      anterior and dorsal anterior cingulate cortices, striatum, ventral tegmental
      area, and posterior parietal cortices. Incongruent responses to JA bids elicited
      increased activity localized to the right temporoparietal junction (TPJ) and
      bilateral cerebellum. No differences in eye-gaze patterns were observed during
      congruent or incongruent trials. Our results highlight the importance of
      utilizing interactive fMRI paradigms in social neuroscience and the impact of
      congruency in recruiting integrated social, reward, and attention circuits for
      processing JA. 

PMID- 24044428
TI  - Magnetic resonance imaging-radioguided occult lesion localization (ROLL) in
      breast cancer using Tc-99m macro-aggregated albumin and distilled water control.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) guided wire localization presents
      several challenges apart from the technical difficulties. An alternative to this
      conventional localization method using a wire is the radio-guided occult lesion
      localization (ROLL), more related to safe surgical margins and reductions in
      excision volume. The purpose of this study was to establish a safe and reliable
      magnetic resonance imaging-radioguided occult lesion localization (MRI-ROLL)
      technique and to report our initial experience with the localization of
      nonpalpable breast lesions only observed on MRI. METHODS: Sixteen women (mean age
      53.2 years) with 17 occult breast lesions underwent radio-guided localization in
      a 1.5-T MR system using a grid-localizing system. All patients had a diagnostic
      MRI performed prior to the procedure. An intralesional injection of Technetium
      99m macro-aggregated albumin followed by distilled water was performed. After the
      procedure, scintigraphy was obtained. Surgical resection was performed with the
      help of a gamma detector probe. The lesion histopathology and imaging
      concordance; the procedure's positive predictive value (PPV), duration time,
      complications, and accuracy; and the rate of exactly excised lesions evaluated
      with MRI six months after the surgery were assessed. RESULTS: One lesion in one
      patient had to be excluded because the radioactive substance came back after the
      injection, requiring a wire placement. Of the remaining cases, there were four
      malignant lesions, nine benign lesions, and three high-risk lesions. Surgical
      histopathology and imaging findings were considered concordant in all benign and
      high-risk cases. The PPV of MRI-ROLL was greater if the indication for the
      initial MR examination was active breast cancer. The median procedure duration
      time was 26 minutes, and all included procedures were defined as accurate. The
      exact and complete lesion removal was confirmed in all (100%) patients who
      underwent six-month postoperative MRI (50%). CONCLUSIONS: MRI-ROLL offers a
      precise, technically feasible, safe, and rapid means for performing preoperative
      MRI localizations in the breast.

PMID- 24044429
TI  - Investigation of the biomechanical effect of variable stiffness shoe on external
      knee adduction moment in various dynamic exercises.
AB  - BACKGROUND: The growing ageing population and high prevalence of knee
      osteoarthritis (OA) in athletes across nations have created a strong demand for
      improved non-invasive therapeutic alternatives for knee OA. The aim of this study
      is to investigate the effect of the variable stiffness shoe (VSS), a new non
      invasive therapeutic approach, on external knee adduction moment (EKAM) in
      various dynamic exercises. EKAM is believed to have positive correlation with the
      progression and development of knee OA. METHODS: Thirty young participants (16
      male and 14 female; age 22.6 +/- 1.9 years) from National University of Singapore
      were enrolled in this study. The tested activities were walking, running, drop
      landing, and lateral hopping. All the dynamic exercises were recorded
      simultaneously by the 8-camera VICON Motion Systems (Oxford Metric, UK) with a
      sampling rate of 100 Hz. RESULTS: The results showed that the EKAM was reduced in
      all the dynamic exercises with the use of VSS. The VSS produced significant
      reductions in the peak EKAM during walking (4.97%, p = 0.039), running (11.15%, p
      = 0.011), drop-landing (11.18%, p = 0.038) and lateral hopping (17.34%, p =
      0.023) as compared to the control shoe. CONCLUSIONS: The reduction of EKAM with
      the use of VSS in various dynamic exercises demonstrates its potential in
      delaying the onset and the progression of knee OA in early stage of knee OA
      patients.

PMID- 24044430
TI  - A molecular model of the full-length human NOD-like receptor family CARD domain
      containing 5 (NLRC5) protein.
AB  - BACKGROUND: Pattern recognition receptors of the immune system have key roles in
      the regulation of pathways after the recognition of microbial- and danger
      associated molecular patterns in vertebrates. Members of NOD-like receptor (NLR)
      family typically function intracellularly. The NOD-like receptor family CARD
      domain containing 5 (NLRC5) is the largest member of this family that also
      contains the largest number of leucine-rich repeats (LRRs).Due to the lack of
      crystal structures of full-length NLRs, projects have been initiated with the aim
      to model certain or all members of the family, but systematic studies did not
      model the full-length NLRC5 due to its unique domain architecture.Our aim was to
      analyze the LRR sequences of NLRC5 and some NLRC5-related proteins and to build a
      model for the full-length human NLRC5 by homology modeling. RESULTS: LRR
      sequences of NLRC5 were aligned and were compared with the consensus pattern of
      ribonuclease inhibitor protein (RI)-like LRR subfamily. Two types of alternating
      consensus patterns previously identified for RI repeats were also found in NLRC5.
      A homology model for full-length human NLRC5 was prepared and, besides the closed
      conformation of monomeric NLRC5, a heptameric platform was also modeled for the
      opened conformational NLRC5 monomers. CONCLUSIONS: Identification of consensus
      patterns of leucine-rich repeat sequences helped to identify LRRs in NLRC5 and to
      predict their number and position within the protein. In spite of the lack of
      fully adequate template structures, the presence of an untypical CARD domain and
      unusually high number of LRRs in NLRC5, we were able to construct a homology
      model for both the monomeric and homo-heptameric full-length human NLRC5 protein.

PMID- 24044431
TI  - A 17 year old male with a testicular fibrothecoma: a case report.
AB  - We herein report the case of a right-sided testicular fibrothecoma in a 17 year
      old male and review the pertinent literature relatable to this rare, benign
      lesion. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:
      http://www.diagnosticpathology.diagnomx.eu/vs/7738283021019280.

PMID- 24044433
TI  - Design, preparation, and implementation of an imidazole-based chiral biaryl P,N
      ligand for asymmetric catalysis.
AB  - A new strategy for increasing the barrier to rotation in biaryls has been
      developed that allows for the incorporation of 5-membered aromatic heterocycles
      into chiral atropisomers. Using this concept, an imidazole-based biaryl P,N
      ligand has been designed and prepared as a single enantiomer. This ligand
      performs exceptionally well in the enantioselective A(3)-coupling, demonstrating
      the potential of this new design element. 

PMID- 24044434
TI  - Selective arylsulfonamide inhibitors of ADAM-17: hit optimization and activity in
      ovarian cancer cell models.
AB  - Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of
      epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM)
      by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and
      invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17
      plays a key role in EGFR signaling and thus may represent a useful target in
      anticancer therapy. Herein we report our hit optimization effort to identify
      potent and selective ADAM-17 inhibitors, starting with previously identified
      inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was
      designed and synthesized. The biological activity of the newly synthesized
      compounds was tested in vitro on isolated enzymes and human EOC cell lines. The
      optimization process led to compound 21, which showed an IC50 of 1.9 nM on ADAM
      17 with greatly increased selectivity. This compound maintained good inhibitory
      properties on sALCAM shedding in several in vitro assays. 

PMID- 24044435
TI  - In vitro reconstitution of peptidoglycan assembly from the Gram-positive pathogen
      Streptococcus pneumoniae.
AB  - Understanding the molecular basis of bacterial cell wall assembly is of paramount
      importance in addressing the threat of increasing antibiotic resistance
      worldwide. Streptococcus pneumoniae presents a particularly acute problem in this
      respect, as it is capable of rapid evolution by homologous recombination with
      related species. Resistant strains selected by treatment with beta-lactams
      express variants of the target enzymes that do not recognize the drugs but retain
      their activity in cell wall building, despite the antibiotics being mimics of the
      natural substrate. Until now, the crucial transpeptidase activity that is
      inhibited by beta-lactams was not amenable to in vitro investigation with enzymes
      from Gram-positive organisms, including streptococci, staphylococci, or
      enterococci pathogens. We report here for the first time the in vitro assembly of
      peptidoglycan using recombinant penicillin-binding proteins from pneumococcus and
      the precursor lipid II. The two required enzymatic activities, glycosyl
      transferase for elongating glycan chains and transpeptidase for cross-linking
      stem-peptides, were observed. Most importantly, the transpeptidase activity was
      dependent on the chemical nature of the stem-peptide. Amidation of the second
      residue glutamate into iso-glutamine by the recently discovered amido-transferase
      MurT/GatD is required for efficient cross-linking of the peptidoglycan. 

PMID- 24044436
TI  - Toward analogues of MraY natural inhibitors: synthesis of 5'-triazole-substituted
      aminoribosyl uridines through a Cu-catalyzed azide-alkyne cycloaddition.
AB  - A straightforward strategy for the synthesis of triazole-containing MraY
      inhibitors has been developed. It involves the sequential introduction of a
      terminal alkyne at the 5' position of an uridine derivative and O-glycosylation
      with a protected aminoribose leading to an elaborated alkyne scaffold. An
      efficient Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) allowed the
      introduction of chemical diversity toward a small library of inhibitors. 

PMID- 24044437
TI  - Characterization of a malaria outbreak in Colombia in 2010.
AB  - BACKGROUND: Although malaria has presented a significant reduction in morbidity
      and mortality worldwide during the last decade, it remains a serious global
      public health problem. In Colombia, during this period, many factors have
      contributed to sustained disease transmission, with significant fluctuations in
      an overall downward trend in the number of reported malaria cases. Despite its
      epidemiological importance, few studies have used surveillance data to describe
      the malaria situation in Colombia. This study aims to describe the
      characteristics of malaria cases reported during 2010 to the Public Health
      Surveillance System (SIVIGILA) of the National Institute of Health (INS) of
      Colombia. METHODS: A descriptive study was conducted using malaria information
      from SIVIGILA 2010. Cases, frequencies, proportions, ratio and measures of
      central tendency and data dispersion were calculated. In addition, the annual
      parasite index (API) and the differences between the variables reported in 2009
      and 2010 were estimated. RESULTS: A total of 117,108 cases were recorded by
      SIVIGILA in 2010 for a national API of 10.5/1,000 habitants, with a greater
      number of cases occurring during the first half of the year. More than 90% of
      cases were reported in seven departments (=states): Antioquia: 46,476 (39.7%);
      Choco: 22,493 (19.2%); Cordoba: 20,182 (17.2%); Valle: 6,360 (5.4%); Guaviare:
      5,876 (5.0%); Narino: 4,085 (3.5%); and Bolivar: 3,590 (3.1%). Plasmodium vivax
      represented ~71% of the cases; Plasmodium falciparum ~28%; and few infrequent
      cases caused by Plasmodium malariae. CONCLUSIONS: Overall, a greater incidence
      was found in men (65%) than in women (35%). Although about a third of cases
      occurred in children <15 years, most of these cases occurred in children >5 years
      of age. The ethnic distribution indicated that about 68% of the cases occurred in
      mestizos and whites, followed by 23% in Afro-descendants, and the remainder (9%)
      in indigenous communities. In over half of the cases, consultation occurred
      early, with 623 complicated and 23 fatal cases. However, the overall incidence
      increased, corresponding to an epidemic burst and indicating the need to
      strengthen prevention and control activities as well as surveillance to reduce
      the risk of outbreaks and the consequent economic and social impact.

PMID- 24044438
TI  - Sugammadex to rescue a 'can't ventilate' scenario in an anticipated difficult
      intubation: is it the answer?

PMID- 24044439
TI  - Left endobronchial intubation with a double-lumen tube using direct laryngoscopy
      or the Trachway(r) video stylet.
AB  - We compared direct laryngoscopy with a Macintosh blade vs indirect bronchoscopy
      with a Trachway(r) stylet, for endobronchial intubation with a left-sided double
      lumen tube. We allocated participants scheduled for thoracic surgery and who had
      normal predicted laryngoscopy, 30 to each group. The mean (SD) intubation times
      with laryngoscope and Trachway were 48 (11) s vs 28 (4) s, respectively, p <
      0.001. The rates of hoarseness on the first postoperative day, categorised as
      none/mild/moderate/severe, were 10/12/7/1 and 22/6/2/0, respectively, p = 0.008,
      without differences on subsequent days. Left endobronchial intubation with a
      double-lumen tube is slower using direct laryngoscopy and causes more hoarseness
      than indirect bronchoscopy with a Trachway stylet.

PMID- 24044440
TI  - Successful use of sugammadex in a 'can't ventilate' scenario.
AB  - A 53-year-old man with hypopharyngeal stenosis following curative
      chemoradiotherapy for a tongue base tumour presented three years later for an
      attempt at pharyngeal dilatation. The first attempt 6 months previously was
      abandoned when awake fibreoptic intubation failed due to partial airway
      obstruction and desaturation when the fibrescope was advanced. As mask
      ventilation was anticipated to be possible, a further attempt at intubation after
      induction of anaesthesia was judged appropriate. The backup plan was jet
      ventilation via a cricothyroid cannula sited pre-induction. However, neither mask
      nor jet ventilation proved possible after the induction of anaesthesia and
      neuromuscular blockade with rocuronium. Swift administration of sugammadex on a
      background of thorough pre-oxygenation allowed return of spontaneous breathing
      before the development of hypoxia and so avoided the need for surgical airway
      rescue. This case demonstrates the utility of sugammadex in restoring spontaneous
      respiration in a 'can't ventilate' scenario, provided that the airway has not
      been traumatised by instrumentation. 

PMID- 24044441
TI  - TAP block--or fascia iliaca spread from supra-inguinal block?

PMID- 24044442
TI  - TAP block--or femoral nerve block?

PMID- 24044443
TI  - TAP block--a block for the future?

PMID- 24044444
TI  - TAP block--what is the endpoint?

PMID- 24044445
TI  - TAP block--or general anaesthesia?

PMID- 24044446
TI  - A reply.

PMID- 24044447
TI  - Bispectral index compared with the isolated forearm technique.

PMID- 24044448
TI  - Bispectral index compared with the isolated forearm technique.